PMID- 28738649
TI  - Well-defined magnetic surface imprinted nanoparticles for selective enrichment of
      2,4-dichlorophenoxyacetic acid in real samples.
AB  - Superparamagnetic core-shell molecularly imprinted polymer nanoparticles (MIPs)
      were prepared via surface initiated reversible-addition fragmentation chain
      transfer (si-RAFT) polymerization for the selective recognition of 2,4
      dichlorophenoxyacetic acid (2,4-D) in real samples. The construction of uniform
      core-shell structure with a 50nm MIP layer was successfully accomplished, which
      favored mass transfer and resulted in fast recognition kinetics. The static
      equilibrium experiments revealed the satisfied adsorption capacity and imprinting
      efficiency of Fe3O4@MIP. Moreover, the Fe3O4@MIP exhibited high selectivity and
      affinity towards 2,4-D over structural analogues. The prepared Fe3O4@MIP
      nanoparticles were used for the selective enrichment of 2,4-D in tap water and
      Chinese cabbage samples. Combined with RP-HPLC, the recoveries of 2,4-D were
      calculated from 93.1% to 103.3% with RSD of 1.7-5.4% (n = 3) in Chinese cabbage
      samples. This work provides a versatile approach for fabricating well-constructed
      core-shell MIP nanoparticles for rapid enrichment and highly selective separation
      of target molecules in real samples.

PMID- 28738650
TI  - Determination of ascorbic acid in serum samples by screen-printed carbon
      electrodes modified with gold nanoparticles.
AB  - This paper shows the ability of simple modified screen-printed devices for the
      electrochemical detection of ascorbic acid in different samples, including serum
      samples. Even if the presence of uric acid does not greatly affect the analysis
      of ascorbic acid using screen-printed carbon electrodes modified by gold
      nanoparticles, dopamine must be considered an interferent. Thus, the joint
      determination of the three compounds has been set out using methods of
      multivariate calibration. The validated models, built by partial least squares
      regressions, have been used to determine the concentration of ascorbic acid,
      dopamine and uric acid of spiked serum samples, with successful results.

PMID- 28738651
TI  - Recent advances in sample pre-treatment for emerging methods in proteomic
      analysis.
AB  - The objective of proteomics is the study of proteins (including their structure
      elucidation, the characterization of their role in biochemical process, the
      detection and identification of anomalous modifications in their structures and
      behavior, etc.) from both a qualitative and quantitative point of view. These
      studies have to face several difficulties as (a) the intrinsic complexity of
      protein molecules, (b) the low concentrations of the studied proteins, (c) the
      complexity of the biological samples (which could lead to interferences from the
      components of these matrixes), etc. Thus, the sample preparation procedure has a
      critical importance in order to obtain good separations and sensitivity in the
      results. In this paper, recent sample treatment methodologies for proteomic
      studies are reviewed and discussed. These methods include recent innovations in
      nanoparticle enrichment pre-treatment (for both the selective pre-concentration
      of the studied protein and the microwave-assisted digestion of the sample),
      treatments for tissue imaging (based on surface analysis of the studied
      biological tissues) and protein microarrays analysis (which allows the
      simultaneous determination of a high number of different proteins or associated
      species on a glass slide support).

PMID- 28738652
TI  - Volatile composition of Merlot red wine and its contribution to the aroma:
      optimization and validation of analytical method.
AB  - A methodology for the determination of volatile compounds in red wine using
      headspace solid phase microextraction (HS-SPME) combined with gas chromatography
      ion trap/ mass spectrometry (GC-IT/MS) and flame ionization detector (GC -FID)
      was developed, validated and applied to a sample of Brazilian red wine. The
      optimization strategy was conducted using the Plackett-Burman design for variable
      selection and central composite rotational design (CCRD). The response surface
      methodology showed that the performance of the extraction of the volatile
      compounds using divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber
      is improved with no sample dilution, the addition of 30% NaCl, applying an
      extraction temperature of 56 degrees C and extraction time of 55min. The
      qualitative method allowed the extraction and identification of 60 volatile
      compounds in the sample studied, notably the classes of esters, alcohols, and
      fatty acids. Furthermore, the method was successfully validated for the
      quantification of 55 volatile compounds of importance in wines and applied to
      twelve samples of Merlot red wine from South of Brazil. The calculation of the
      odor activity value (OAV) showed the most important components of the samples
      aroma. Ethyl isovalerate, ethyl hexanoate, 1-hexanol, octanoic acid and ethyl
      cinnamate had the greatest contribution to the aroma of the wines analyzed, which
      is predominantly fruity with the presence of herbal and fatty odors.

PMID- 28738653
TI  - Development of an efficient method for multi residue analysis of 160 pesticides
      in herbal plant by ethyl acetate hexane mixture with direct injection to GC
      MS/MS.
AB  - A simple and efficient multi residue method was developed, for the analysis of
      160 pesticides by GC-MS/MS in herbal plants. The developed method employs
      pesticide residue extraction by EtAC/ n. hexane (6:4) with a cleanup step using
      florisil/ PSA mixture. The optimized conditions have resulted in lower co
      extracted matrix components than those extracted using EtAC or MeCN (QuEChERS
      method), according to FTIR and full scan GC/MS analyses. In addition, the
      developed method (EtAC/ Hexane) eliminates the evaporation step that is usually
      performed when using MeCN as an extraction solvent prior to the GC-MS/MS
      injection. The developed method was fully validated on chamomile, based on
      SANTE/11945/2015 guidelines. Where, intraday recoveries were estimated at three
      concentration levels of 10, 50 and 250MUgkg-1. However, interday recoveries have
      also been carried out, at 250MUgkg-1. In addition, intraday recoveries were
      estimated for two other herbal plants (thyme and marjoram), at 250MUgkg-1. Three
      point calibration mixtures were prepared in ethyl acetate solvent and in the
      blank extracts of chamomile, thyme, and marjoram, in order to check the linearity
      and matrix effect. The average recoveries for most of the studied pesticides
      ranged from 70% to 100% at 50 and 250MUgkg-1 with relative standard deviations
      below 20%. The validated method was successfully applied for determination of
      pesticide residues in 20 herb samples, collected from the Egyptian market.

PMID- 28738654
TI  - Development of a sensitive and quantitative UHPLC-MS/MS method to study the whole
      body uptake of pharmaceuticals in zebrafish.
AB  - An analytical procedure to measure the whole-body uptake of pharmaceuticals in
      zebrafish has been developed using state-of-the-art methodologies. A sample
      preparation procedure for 9 pharmaceuticals displaying a variety in
      physicochemical properties was developed using 10-day old zebrafish (TG898). For
      an efficient homogenization of the samples and subsequent recovery of the
      compounds of interest, different amounts of organic solvents in combination with
      acidic modifiers were added to zebrafish samples. Samples were subsequently
      processed using a powerful bath sonicator and centrifuged. Supernatant was then
      removed and evaporated in a vacuum oven before being reconstituted in a mobile
      phase-like solvent. Samples were analyzed using ultra-high performance liquid
      chromatography (UHPLC) on an Acquity BEH C18 column (100 * 2.1mm, dp=1.7um)
      coupled to a Waters Xevo TQ-S mass spectrometer. For this purpose, a generic
      gradient was run, wherein the percentage of acetonitrile was varied from 3% to
      82% in 10.5min at a flow rate of 0.41mL/min. Linearity of the method was
      demonstrated for all compounds (R2 > 0.997) in a practically relevant
      concentration range. Matrix effects were between 81% and 106%, except for
      amitriptyline (51%). Using this method, it was demonstrated that a sample
      pretreatment using 1:2 (v/v) water:methanol in combination with 0.1% formic acid
      resulted in acceptable recoveries between 74% and 100% for all compounds.
      Together with the obtained lower limits of quantification of the analytical
      method (between 0.005 and 1.5ng/mL), this allowed the use of a single zebrafish
      to study the whole-body uptake of a particular drug, after incubating zebrafish
      at the maximum tolerated concentration for this drug.

PMID- 28738655
TI  - Risk of false decision on conformity of a multicomponent material when test
      results of the components' content are correlated.
AB  - The probability of a false decision on conformity of a multicomponent material
      due to measurement uncertainty is discussed when test results are correlated.
      Specification limits of the components' content of such a material generate a
      multivariate specification interval/domain. When true values of components'
      content and corresponding test results are modelled by multivariate distributions
      (e.g. by multivariate normal distributions), a total global risk of a false
      decision on the material conformity can be evaluated based on calculation of
      integrals of their joint probability density function. No transformation of the
      raw data is required for that. A total specific risk can be evaluated as the
      joint posterior cumulative function of true values of a specific batch or lot
      lying outside the multivariate specification domain, when the vector of test
      results, obtained for the lot, is inside this domain. It was shown, using a case
      study of four components under control in a drug, that the correlation influence
      on the risk value is not easily predictable. To assess this influence, the
      evaluated total risk values were compared with those calculated for independent
      test results and also with those assuming much stronger correlation than that
      observed. While the observed statistically significant correlation did not lead
      to a visible difference in the total risk values in comparison to the independent
      test results, the stronger correlation among the variables caused either the
      total risk decreasing or its increasing, depending on the actual values of the
      test results.

PMID- 28738656
TI  - An ultrasensitive fluorescent nanosensor for trypsin based on upconversion
      nanoparticles.
AB  - Trypsin and its inhibitors are relevant to many physiological processes and
      diseases. In this study, a nanosensor capable of detecting trypsin and its
      inhibitors was designed based on the fluorescence resonance energy transfer
      (FRET) between upconversion nanoparticle (UCNP) and gold nanoparticle (AuNP).
      UCNP and AuNP were linked by a trypsin-sensitive peptide DDDDARC, forming the non
      fluorescent UCNP-peptide-AuNP nanosensor. In the presence of trypsin, the peptide
      was cleaved and the quenched fluorescence was restored; in the presence of
      trypsin inhibitors, the recovery of the fluorescence was decreased. The
      nanosensor showed a superb sensitivity and selectivity for trypsin and its
      inhibitors, with a detection limit of 4.15ngmL-1 for trypsin. UCNP-peptide-AuNP
      could eliminate the interference of background fluorescence and avoid the light
      toxicity, and potentially be used to diagnose trypsin-related diseases or screen
      trypsin inhibitors.

PMID- 28738657
TI  - A new strategy for fabrication of water dispersible and biodegradable fluorescent
      organic nanoparticles with AIE and ESIPT characteristics and their utilization
      for bioimaging.
AB  - Fluorescence probes play a crucial role in optical imaging for visualization of
      complex biological processes. As compared with conventional organic fluorogens,
      the probes with aggregation-induced emission (AIE) and excited-state
      intramolecular proton transfer (ESIPT) characteristics show significant
      advantages in high quantum yield at concentrated and aggregated state, large
      Stokes shift and low cytotoxicity. However, the synthesis of AIE-active
      fluorescent probes through the ESIPT mechanism has received only very limited
      attention. On the other hand, the preparation of biodegradable fluorescent probes
      through the ESIPT mechanism has not been demonstrated thus far. In this work, we
      reported for the first time that water dispersible and biodegradable fluorescent
      polymeric nanoparticles with AIE and ESIPT characteristics could be facilely
      obtained through conjugation of 2,4-Dihydroxybenzophenone based benzophenone
      azine (BPA) and polyethylene glycol (PEG) using hexamethylene diisocyanate. The
      final copolymers contained hydrophilic and biocompatible PEG and biodegradable
      urethane linkage are readily self-assembled into core-shell nanostructures.
      Moreover, the self-assembled BPA-PEG2000 fluorescent organic nanoparticles (FONs)
      displayed obvious AIE feature, high water dispersibility, superb
      biocompatibility, biodegradability and excellent cell dyeing performance. All of
      the above properties implied that BPA-PEG2000 FONs are promising candidates for a
      variety of biomedical applications.

PMID- 28738658
TI  - An ultrasensitive chemiluminescence aptasensor for thrombin detection based on
      iron porphyrin catalyzing luminescence desorbed from chitosan modified magnetic
      oxide graphene composite.
AB  - In this work, an ultrasensitive chemiluminescence (CL) aptasensor was prepared
      for thrombin detection based on iron porphyrin catalyzing luminol - hydrogen
      peroxide luminescence under alkaline conditions, and iron porphyrin was desorbed
      from chitosan modified magnetic oxide graphene composite (CS@Fe3O4@GO). Firstly,
      CS@Fe3O4@GO was prepared. CS@Fe3O4@GO has advantages of the good biocompatibility
      and positively charged on its surface of CS, the large specific surface area of
      GO and the easy separation characteristics of Fe3O4. GO, Fe3O4 and CS@Fe3O4@GO
      were confirmed by transmission electron microscopy (TEM), scanning electron
      microscope (SEM), fourier transform infrared (FTIR) and X-ray powder diffraction
      (XRD). Then, thrombin aptamer (T-Apt) and hemin (HM, an iron porphyrin) were
      sequentially modified on the surface of CS@Fe3O4@GO to form CS@Fe3O4@GO@T-Apt@HM.
      The immobilization properties of CS@Fe3O4@GO to T-Apt and adsorption properties
      of CS@Fe3O4@GO@T-Apt to HM were sequentially researched through the curves of
      kinetics and the curves of thermodynamics. When thrombin existed in solutions, HM
      was desorbed from the surface of CS@Fe3O4@GO@T-Apt@HM owing to the strong
      specific recognition ability between thrombin and T-Apt, causing the changes of
      CL signal. Under optimized CL conditions, thrombin could be measured with the
      linear concentration range of 5.0*10-15-2.5*10-10mol/L. The detection limit was
      1.5*10-15mol/L (3delta) while the relative standard deviation (RSD) was 3.2%.
      Finally, the CS@Fe3O4@GO@T-Apt@HM-CL aptasensor was used for the determination of
      thrombin in practical serum samples and recoveries ranged from 95% to 103%. Those
      satisfactory results revealed potential application of the CS@Fe3O4@GO@T-Apt@HM
      CL aptasensor for thrombin detection in monitoring and diagnosis of human blood
      diseases.

PMID- 28738659
TI  - Sample treatment in Mossbauer spectroscopy for protein-related analyses:
      Nondestructive possibilities to look inside metal-containing biosystems.
AB  - In this review, the unique possibilities are considered of the 57Fe transmission
      (TMS) and 57Co emission (EMS) variants of Mossbauer (nuclear gamma-resonance)
      spectroscopy as nondestructive techniques with minimal sample
      preparation/treatment and a significant analytical potential, with a focus on the
      analysis of cation-binding sites in metalloproteins. The techniques are shown to
      provide unique structural and quantitative information on the coordination
      microenvironment, the chemical state and transformations of the Mossbauer
      nuclides in sophisticated metal-containing proteins, including those within
      complicated supramolecular structures, and in microbial cells or tissues. Recent
      representative examples of analyses of Fe-containing proteins by 57Fe TMS are
      briefly discussed, along with the newly emerging data on using 57Co EMS for
      probing the structural organisation of 57Co-doped cation-binding sites in
      sophisticated biocomplexes including metalloenzymes. Finally, some rare or exotic
      applications of Mossbauer spectroscopy (including the synchrotron-based
      methodology) in protein-related studies are outlined.

PMID- 28738660
TI  - Novel biomimetic enzyme for sensitive detection of superoxide anions.
AB  - Superoxide anion (O2*-), one of the most active reactive oxygen species (ROS) in
      micro-environment of the human body, is involved in some diseases if there is
      excess O2*- associated with oxidative stress. Accurate detection of its
      concentration has important medical diagnostic significance. In this work, a new
      electrochemical sensor was designed and fabricated for sensitive detection based
      on Mn-superoxide dismutase (MnSOD) that decorated onto the surface of magnetic
      polymeric nanotubes by surface self-assembly processes. The composite nanotubes
      were characterized by transmission electron microscopy (TEM), fourier transform
      infrared spectroscopy (FTIR), Zeta potential analyzer, energy dispersive
      spectroscopy (EDS) and vibrating sample magnetometer(VSM), and the biosensor
      exhibited excellent analytical performance, for example, the interference could
      be eliminated with high selectivity, the linear range from 0.15 to 3.0MUM with a
      detection limit of 0.0136MUM (S/N=3),Cyclic voltammogram (CV) curves of the
      biosensor for 30 overlapping cycles showed the biosensor had a good cycle
      stability. Results indicated that the magnetic polymeric nanotubes that decorated
      by Mn3(PO4)2 nanoparticles could effectively catalyze the dismutation of O2*-
      that attributed to its high surface areas and a large number of active sites of
      self-assembled Mn3(PO4)2 nanoparticles. This method combining nanotechnology and
      self-assembly technique provided a new appropriate platform to design and
      fabricate electrochemical sensor with high performance.

PMID- 28738661
TI  - Semiautomatic sequential extraction of polycyclic aromatic hydrocarbons and
      elemental bio-accessible fraction by accelerated solvent extraction on a single
      particulate matter sample.
AB  - We describe the optimization and validation of a sequential extractive method for
      the determination of the polycyclic aromatic hydrocarbons (PAHs) and elements
      (Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Se, V and Zn) that are chemically
      fractionated into bio-accessible and mineralized residual fractions on a single
      particulate matter filter. The extraction is performed by automatic accelerated
      solvent extraction (ASE); samples are sequentially treated with
      dichloromethane/acetone (4:1) for PAHs extraction and acetate buffer (0.01M; pH
      4.5) for elements extraction (bio-accessible fraction). The remaining solid
      sample is then collected and subjected to acid digestion with HNO3:H2O2 (2:1) to
      determine the mineralized residual element fraction. We also describe a homemade
      ASE cell that reduces the blank values for most elements; in this cell, the steel
      frit was replaced by a Teflon pierced disk and a Teflon cylinder was used as the
      filler. The performance of the proposed method was evaluated in terms of recovery
      from standard reference material (SRM 1648 and SRM 1649a) and repeatability. The
      equivalence between the new ASE method and conventional methods was verified for
      PAHs and for bio-accessible and mineralized residual fractions of elements on
      PM10 twin filters.

PMID- 28738662
TI  - Highly efficient enrichment of low-abundance intact proteins by core-shell
      structured Fe3O4-chitosan@graphene composites.
AB  - In proteomics research, the screening and monitoring of disease biomarkers is
      still a major challenge, mainly due to their low concentration in biological
      samples. However, the universal enrichment of intact proteins has not been
      further studied. In this work, we developed a Fe3O4-chitosan@graphene (Fe3O4
      CS@G) core-shell composite to enrich low-abundance proteins from biological
      samples. Fe3O4-CS@G composite holds chitosan layer decorated Fe3O4 core, which
      improves the hydrophilicity of materials greatly. Meanwhile, the graphene
      nanosheets shell formed via electrostatic assembly endows the composite with huge
      surface area (178m2/g). The good water dispersibility ensures the sufficient
      contact opportunities between graphene composites and proteins, and the large
      surface area provides enough adsorption sites for the enrichment of proteins.
      Using Fe3O4-CS@G, four standard proteins Cyt-c, BSA, Myo and OVA were enriched
      with better adsorption capacity and recovery rate, compared with previously
      reported magnetic graphene composites. Additionally, the mechanism of compared
      to" is corrected into "compared with". proteins adsorption on Fe3O4-CS@G was
      further studied, which indicates that hydrophobic and electrostatic interaction
      work together to facilitate the universal and efficient enrichment of proteins.
      Human plasma sample was employed to further evaluate the enrichment performance
      of Fe3O4-CS@G. Eventually, 123 proteins were identified from one of SAX fractions
      of human plasma, which is much better than commercial Sep-pak C18 enrichment
      column (39 proteins). All these outstanding performances suggest that Fe3O4-CS@G
      is an ideal platform for the enrichment of low-abundance intact proteins and thus
      holds great potential to facilitate the identification of biomarkers from
      biological samples in proteomics research.

PMID- 28738663
TI  - Statistical approach for ATR-FTIR screening of semen in sexual evidence.
AB  - Genetic identification has revolutionized the Forensic Sciences, especially in
      sexual aggression cases. For the successful extraction of the genetic information
      of a criminal, a crucial step is the prior detection of bodily fluids on
      evidence. In this article, a method for non-destructive screening of semen
      samples is reported. Using chemometric tools, bodily fluids can be detected and
      differentiated without damaging the sample, by correlating the infrared spectra
      of sexual evidence with previously recorded spectra from undamaged stains of
      individual bodily fluids. In modern hospitals/laboratories, the proposed method
      would not require additional equipment/material nor specialized personnel.
      Furthermore, the method provides qualitative and reliable results, without
      requiring human interpretation. Therefore, the proposed method opens a door for a
      low-cost, fully automated and efficient system for non-destructive screening of
      semen, which could be easily and massively implemented.

PMID- 28738664
TI  - Bomb swab: Can trace explosive particle sampling and detection be improved?
AB  - The marked increase in international terror in recent years requires the
      development of highly efficient methods to detect trace amounts of explosives at
      airports, border crossings and check points. The preferred analytical method
      worldwide is the ion mobility spectrometry (IMS) that is capable of detecting
      most explosives at the nano-gram level. Sample collection for the IMS analysis is
      based on swabbing of a passenger's belongings to collect possible explosive
      residues. The present study examines a wide range of issues related to swab-based
      particle collection and analysis, in the hope of gaining deeper understanding
      into this technique that will serve to improve the detection process. The
      adhesion of explosive particles to three typical materials, plastic, metal and
      glass, were measured using atomic force microscopy (AFM). We found that a strong
      contribution of capillary forces to adhesion on glass and metal surfaces renders
      these substrates more promising materials upon which to find and collect
      explosive residues. The adhesion of explosives to different swipe materials was
      also examined. Here we found that Muslin, Nomex(r) and polyamide membrane
      surfaces are the most promising materials for use as swipes. Subsequently, the
      efficiency of multiple swipe use - for collecting explosive residues from a glass
      surface using Muslin, Nomex(r) and TeflonTM swipes - was examined. The study
      suggests that swipes used in about 5-10 "sampling and analysis cycles" have
      higher efficiency as compared to new unused swipes. The reason for this behavior
      was found to be related to the increased roughness of the swipe surface following
      a few swab measurements. Lastly, GC-MS analysis was employed to examine the
      nature of contaminants collected by the three types of swipe. The relative
      amounts of different contaminants are reported. The existence and interference of
      these contaminants have to be considered in relation to the detection efficiency
      of the various explosives by the IMS.

PMID- 28738665
TI  - Aggregation Control by Multi-stimuli-Responsive Poly(N-vinylamide) Derivatives in
      Aqueous System.
AB  - Thermal and photo responsive copolymer based on N-vinylamide backbone was
      designed. Methoxyethyl group and azobenzene were selected to improve
      hydrophilicity and photoresponsive moieties, respectively. The N-(methoxyethyl)-N
      vinylformamide was synthesized and copolymerized with N-vinylformamide by free
      radical polymerization. In order to control the nanosized structures, poly(N
      vinylformamide) derivatives bearing azobenzene at the N-position near to the
      vinyl polymer main chain were synthesized by polymer reaction with the poly(N
      vinylformamide-co-N-(methoxyethyl)-N-vinylformamide) and azobenzene. Aggregation
      size of the multi-stimuli-responsive polymer was controlled by preparation of the
      hydrophobic interaction at around N-position.

PMID- 28738666
TI  - Influence of kitesurf equipment on injury rates.
AB  - BACKGROUND: Various injuries in kitesurfing (KS) have been reported so far. The
      aim of this study was to validate the effect of different kite designs and safety
      equipment on the injury rate compared to older studies. METHODS: A retrospective
      epidemiological study based on an anonymous face-to-face survey was conducted
      amongst active kitesurfers. The questionnaire consisted of 66 questions focusing
      on the equipment used, injury rates, overuse injuries and gender differences. A
      stepwise Poisson-Model was used to identify injury-associated factors. RESULTS: A
      total of 202 kitesurfers with a mean age of 31.8+/-9.1 years and 698.2+/-931.5
      hours of KS experience were included. 2613 injuries were recorded (18.5/1000
      hours KS). Almost 50% were hematomas, bruises or cuts. 3.9% of all injuries
      (0.71/1000 hours KS) were time-loss injuries of more than one week. Female
      kitesurfers had a significantly greater injury rate, were less experienced and
      fewer of them used C-kites. Height, weight, primary kite spot, experience,
      physical activity, warm-up/stretching, the type of kite and control bar used, and
      the use of a board leash were independent factors associated to injury rate. The
      lower extremity, the elbow, thorax and abdomen were at risk for overuse injuries.
      CONCLUSIONS: An influence of equipment on injuries could be statistically shown.
      The overall injury rate in KS did not decline in the last decades, but time-loss
      injuries did.

PMID- 28738667
TI  - Toe grip strength in middle-aged individuals as a risk factor for falls.
AB  - BACKGROUND: Toe grip strength is the force of a toe on a surface. The objective
      of this study was to investigate the relationship between falls in middle-aged
      individuals and physical strength factors such as toe grip strength and knee
      extension strength. METHODS: The subjects were 194 middle-aged individuals (388
      feet) who were independent in daily life, received no nursing care, and
      participated in a health sports event organized by a sports club. We evaluated
      the body composition, blood pressure, vascular age, systemic response, bone
      density, knee extension strength, and toe grip strength, and examined their
      relationship using a self-administered questionnaire survey. RESULTS: The fall,
      near-fall, and no fall groups included 7, 36, and 151 subjects, respectively; the
      high and low risk groups included 43 and 151 subjects, respectively. Logistic
      regression analysis was performed with risk of falls as the dependent variable,
      and factors that showed a significant difference in the comparison of the high
      and low risk groups as independent variables. In this analysis, toe grip strength
      and diastolic blood pressure were identified as independent risk factors for a
      fall. CONCLUSIONS: Toe grip strength is an independent risk factor for falls, and
      improvement of toe grip strength might prevent falls.

PMID- 28738668
TI  - Study of the effects of multimodal exercise program on physical fitness and
      health perception in community-living Hungarian older adults.
AB  - BACKGROUND: The aim of this study was to investigate the effects on fitness
      indicators and subjective health-perception of a multimodal exercise program
      provided by a district in Budapest among community-living seniors. METHODS: Sixty
      community-living older adults aged over 60 years formed beginner group (who were
      at the beginning of the exercise program), advanced group (who had been in the
      programme for 3-6 months), active group (who had been participating in the
      exercise program for at least 6 months, in addition to Nordic walking program)
      and a physically inactive control group. Balance, functional mobility, lower and
      upper limb strength, lower and upper body flexibility, aerobic endurance and self
      reported health perception were measured at baseline, and after a 12-week follow
      up period. RESULTS: The beginner group and the advanced group improved in upper
      body flexibility (beginner Delta=1.2; d=0.83; advanced: Delta=1.7; d=1.39), lower
      body flexibility (beginner: Delta=1.7, d=0.484; advanced: Delta=1.9; d=1.55),
      lower limb strength (beginner: Delta=1.47; d=0.84; advanced: Delta=1.57; d=0.72),
      and functional mobility (beginner: Delta=-0.6; d=0.54; advanced: Delta=-0.4;
      d=0.90). There were also improvements in aerobic endurance (Delta=11.06; d=0.96)
      and balance (Delta=1.6; d=0.62) of beginner group. These indicators declined in
      the control group. Indicators of the active group did not change. The self
      perceived health status declined (Delta=-13.9; d=0.73) in the control group but
      did not change in any exercising groups. CONCLUSIONS: This multimodal exercise
      program can be effective among community-living older adults, even in Hungary, a
      country where geriatric physical activity is not widespread. Therefore, it would
      be useful to extend this model program to other settlements as well.

PMID- 28738669
TI  - Evaluation of the effectiveness of a transfer (interhemispheric) training program
      in the early stages of fencing training.
AB  - BACKGROUND: A high level of motor coordination (with an emphasis on the accuracy
      of hand movements) is an important part of fencers' training. Research on motor
      coordination shows that both hemispheres of the brain are involved in controlling
      the action of each of the upper limbs. As the physical training of one hand is
      believed to significantly increase the performance of the other (untrained) hand,
      the authors attempt to verify the hypothesis that specialized training of the non
      dominant limb can improve the performance of the dominant hand in fencing.
      METHODS: The study was carried out in Poznan, Poland, in 2015 and involved the
      experimental (N.=8) and control (N.=8) groups of cadets (12.7+/-0.5 years old);
      body mass 38.69+/-4.08; body height 153.47+/-6.17), who were randomly selected
      from fencers belonging to the Fencing Club "Warta" in Poznan, Poland.
      Participants in the study belonged to one training group with a similar training
      experience of about 6 years. All participants in the study (N.=16) declared right
      handedness during trainings and duels. Their right lateralization was also
      confirmed in a survey, which was conducted using the Edinburgh Questionnaire. The
      experimental training program included six weeks of specialized training of the
      coordination skills of the non-dominant side. It was carried out five times a
      week. Each session took 30 minutes. The aim of the study was to determine the
      effect of transfer (interhemispheric) training with the use of the non-dominant
      hand in particular, on the performance of the dominant hand in fencing. RESULTS:
      The results indicate that the transfer (interhemispheric) training reduced test
      accomplishment time in tasks performed with the right upper limb during accuracy
      tests. The procedures applied in the study also reduced test accomplishment time
      in tasks performed with the left upper limb. CONCLUSIONS: The study demonstrates
      that an interhemispheric training program can effectively improve the accuracy of
      fencing actions, at least in the early stages of training.

PMID- 28738670
TI  - Antidoping program: an important factor in the promotion and protection of the
      integrity of sport and athlete's health.
AB  - Using performance-enhancing drugs concerns not only elite Olympic and Paralympic
      Games' athletes but also amateur athletes, who are making increasing use of
      substances and/or methods. Furthermore, a new frontier reached by the doping is
      the use of genes. World Anti-Doping Agency expressly prohibited the participation
      in competitive sports by the athlete in case of taking banned substances to treat
      disease in the event that the above assumption implies an excessive improvement
      of performance. This study aims to analyze and show the doping control as an
      essential part of the antidoping program to promote and protect the integrity of
      sport and athlete's health. Testing is carried out in accordance with the World
      Anti-Doping Code (WADC) and several international standards (ISs). The ISs were
      developed for laboratories, testing, the prohibited list, and for therapeutic use
      exemptions. It seems that the 2009 version of the WADC obliges all the healthcare
      professionals not to assist athletes engaged in doping behaviours; they can be
      removed from working with athletes. Many people do not know doping's dangerous
      effects on health. It is necessary, therefore, to implement the knowledge on this
      issue through public and sports institutions information and awareness campaigns.
      For this reason, local institutions and the National Olympic Committee shall give
      tools, in particular economic, to carry out the work of education, training, and
      control.

PMID- 28738671
TI  - Inertial flywheel resistance training and muscle oxygen saturation.
AB  - BACKGROUND: The inertial flywheel device causes an increase in eccentric overload
      during training. The aim was to study muscle oxygen saturation produced during an
      inertial flywheel squat training, comparing it with a barbell squat training.
      METHODS: Twelve male adults performed a barbell squat training (3*8 reps, 75-80%
      1RM) and a flywheel squat training (3*8 reps, all-out). Muscle oxygen saturation
      (%SmO2), total hemoglobin (tHb), reoxygenation, heart rate (HR), lactate,
      vertical jumps, maximal voluntary isometric contraction and rated perceived
      exertion (RPE) were studied. RESULTS: Both protocols produced a significant
      decrease in %SmO2 and tHB during the sets of squats, and a significant increase
      in HR, lactates dand RPE after training. The flywheel squat protocol caused a
      greater decrease in %SmO2 than the barbell squat protocol in each of the sets of
      exercises (1st set: -67.5+/-7.2% vs. -53.7+/-16.2%; 2nd set: -67.2+/-13.5% vs. 
      53.6+/-15.4%; 3rd set: -68.1+/-13.0% vs. -55.0+/-17.0%), as well as a longer
      reoxygenation after finishing the training (61.7+/-12.6 vs. 55.7+/-13.7 s).
      CONCLUSIONS: Although no differences were found on a muscle fatigue level, the
      flywheel training brought on greater physiological stress than the barbell squat
      training, observing a greater decrease in muscle oxygen saturation and a longer
      reoxygenation.

PMID- 28738672
TI  - Physiological and physical responses to wearing compression garments during
      soccer matches and recovery.
AB  - BACKGROUND: There is not enough information on the effects of compression therapy
      in soccer players during recovery after matches. The objective of this study was
      to examine the effect of wearing compression garments during soccer matches and
      during recovery period on physical responses. METHODS: Eighteen semi-professional
      soccer players participated in this study. A two-stage crossover design was
      chosen. Participants acted as controls in one match and were assigned to an
      experimental group (compression stockings group, full-leg compression group,
      shorts group) in the other match. Participants in experimental groups played the
      match wearing assigned compression garments and were worn in the 3 days post
      match, for 7 hours/day. Blood lactate concentration, arterial oxygen saturation
      of hemoglobin, perceived exertion, perceived recovery, anaerobic power (vertical
      jump, sprint, change of direction) and aerobic capacity (Yo-Yo Intermittent
      Recovery level 2) were measured. Internal and external loads were measured during
      both matches. RESULTS: Using compression garments may slightly increase lactate
      during and after soccer matches and only full-leg garments can moderately
      attenuate the reduction of arterial oxygen saturation of hemoglobin. Wearing
      compression garments can be useful between 24-48 hours post-exercise to promote
      psychological recovery, especially with full-leg garments and compression shorts.
      Decreases in anaerobic power can be attenuated but not significantly, mainly with
      full-leg compression garments or compression shorts. Compression garments could
      also have positive effect on aerobic capacity, but we cannot exclude a placebo
      effect. CONCLUSIONS: Compression garments could be moderately beneficial, but
      effects are not significant.

PMID- 28738673
TI  - Promoter Effects of Alkali Metal Cations on the Electrochemical Reduction of
      Carbon Dioxide.
AB  - The electrochemical reduction of CO2 is known to be influenced by the identity of
      the alkali metal cation in the electrolyte; however, a satisfactory explanation
      for this phenomenon has not been developed. Here we present the results of
      experimental and theoretical studies aimed at elucidating the effects of
      electrolyte cation size on the intrinsic activity and selectivity of metal
      catalysts for the reduction of CO2. Experiments were conducted under conditions
      where the influence of electrolyte polarization is minimal in order to show that
      cation size affects the intrinsic rates of formation of certain reaction
      products, most notably for HCOO-, C2H4, and C2H5OH over Cu(100)- and Cu(111)
      oriented thin films, and for CO and HCOO- over polycrystalline Ag and Sn.
      Interpretation of the findings for CO2 reduction was informed by studies of the
      reduction of glyoxal and CO, key intermediates along the reaction pathway to
      final products. Density functional theory calculations show that the alkali metal
      cations influence the distribution of products formed as a consequence of
      electrostatic interactions between solvated cations present at the outer
      Helmholtz plane and adsorbed species having large dipole moments. The observed
      trends in activity with cation size are attributed to an increase in the
      concentration of cations at the outer Helmholtz plane with increasing cation
      size.

PMID- 28738674
TI  - Complex Consisting of beta-Glucan and Antigenic Peptides with Cleavage Site for
      Glutathione and Aminopeptidases Induces Potent Cytotoxic T Lymphocytes.
AB  - The efficient induction of antigen-specific immune responses requires not only
      promotion of the uptake of antigens and adjuvant molecules into antigen
      presenting cells but also control of their intracellular behavior. We previously
      demonstrated that the beta-glucan schizophyllan (SPG) can form complexes with CpG
      oligonucleotides with attached dA40 (CpG-dA/SPG), which can accumulate in
      macrophages in the draining inguinal lymph nodes and induce strong immune
      responses. In this study, we prepared various conjugates composed of antigenic
      peptide (OVA257-264) and dA40 and made complexes with SPG. The conjugates with a
      disulfide bond between OVA257-264 and dA40 were easily cleaved by glutathione.
      The resultant peptides with a hydrophobic amino acid at the C-terminal end was
      recognized by puromycin-insensitive leucine aminopeptidase (PILS-AP), which trims
      antigenic peptide precursors and prepares peptides of eight or nine amino acids
      in length, which is the optimal length for binding to major histocompatibility
      complex (MHC)-I. The conjugate exposed to such enzymes induced a high antigen
      presentation level. The antigen presentation level was almost the same before and
      after the complexation with SPG. Immunization with a mixture of dA-OVA257-264/SPG
      and CpG-dA/SPG induced high antigen-specific cytotoxic T-lymphocyte activity at a
      much lower peptide dose than in previous studies. These results can be strongly
      ascribed to not only the cell-specific delivery by SPG but also the control of
      the intracellular behavior by the introduction of cleavage sites. Therefore,
      peptide-dA/SPG complexes could be used as potent vaccine antigens for the
      treatment of cancers and infectious diseases.

PMID- 28738675
TI  - Transparent and Flexible Triboelectric Sensing Array for Touch Security
      Applications.
AB  - Tactile sensors with large-scale array and high sensitivity is essential for
      human-machine interaction, smart wearable devices, and mobile networks. Here, a
      transparent and flexible triboelectric sensing array (TSA) with fingertip-sized
      pixels is demonstrated by integrating ITO electrodes, FEP film, and signal
      transmission circuits on an undivided palm-sized polyethylene terephthalate
      substrate. The sensing pixels can be triggered by the corresponding external
      contact to induce the electrostatic potential in the transparent electrodes
      without power consumption, which is individually recognized by the sensor. By
      testing the response of the pixels, the electrical characterization is
      systematically investigated. The proposed TSA exhibits excellent durability,
      independence, and synchronicity, which is able to realize real-time touch
      sensing, spatial mapping, and motion monitoring. The integrated TSA has great
      potential for an active tactile system, human-machine interface, wearable
      electronics, private communication, and advanced security identification.

PMID- 28738676
TI  - In Situ Crystallization of the Insoluble Anhydrite AII Phase in Graphene Pockets.
AB  - Single-distilled water encapsulated in graphene pockets has been studied by
      aberration-corrected high-resolution transmission electron microscopy and
      electron energy loss spectroscopy at an acceleration voltage of 80 kV. Inside the
      graphene pockets, crystallization and in situ crystal growth are reported and
      identified as the insoluble AII phase of CaSO4 (anhydrite) in a quasi-two
      dimensional system. Its formation condition is discussed with respect to the
      possible temperature and van der Waals pressure between the graphene sheets.

PMID- 28738678
TI  - Density Functional Theory for Electron Gas and for Jellium.
AB  - Density functional theory relies on universal functionals characteristic of a
      given system. Those functionals in general are different for electron gas and for
      jellium (electron gas with a uniform background). However, jellium is frequently
      used to construct approximate functionals for an electron gas (e.g., local
      density approximation and gradient expansions). The precise relationship of the
      exact functionals for the two systems is addressed here. In particular, it is
      shown that the exchange-correlation functionals for the inhomogeneous electron
      gas and inhomogeneous jellium are the same. This justifies theoretical and
      quantum Monte Carlo simulation studies of jellium to guide the construction of
      functionals for an electron gas. Related issues of the thermodynamic limit are
      noted as well.

PMID- 28738677
TI  - Quantitation of 87 Proteins by nLC-MRM/MS in Human Plasma: Workflow for Large
      Scale Analysis of Biobank Samples.
AB  - A multiple reaction monitoring (MRM) assay was developed for precise quantitation
      of 87 plasma proteins including the three isoforms of apolipoprotein E (APOE)
      associated with cardiovascular diseases using nanoscale liquid chromatography
      separation and stable isotope dilution strategy. The analytical performance of
      the assay was evaluated and we found an average technical variation of 4.7% in 4
      5 orders of magnitude dynamic range (~0.2 mg/L to 4.5 g/L) from whole plasma
      digest. Here, we report a complete workflow, including sample processing adapted
      to 96-well plate format and normalization strategy for large-scale studies. To
      further investigate the MS-based quantitation the amount of six selected proteins
      was measured by routinely used clinical chemistry assays as well and the two
      methods showed excellent correlation with high significance (p-value < 10e-5) for
      the six proteins, in addition for the cardiovascular predictor factor, APOB:
      APOA1 ratio (r = 0.969, p-value < 10e-5). Moreover, we utilized the developed
      assay for screening of biobank samples from patients with myocardial infarction
      and performed the comparative analysis of patient groups with STEMI (ST- segment
      elevation myocardial infarction), NSTEMI (non ST- segment elevation myocardial
      infarction) and type-2 AMI (type-2 myocardial infarction) patients.

PMID- 28738679
TI  - Probability of Two-Step Photoexcitation of Electron from Valence Band to
      Conduction Band through Doping Level in TiO2.
AB  - For an Ir-doped TiO2 (Ir:TiO2) photocatalyst, we examined the most dominant
      electron-transfer path for the visible-light-driven photocatalytic performance.
      The Ir:TiO2 photocatalyst showed a much higher photocatalytic activity under
      visible-light irradiation than nondoped TiO2 after grafting with the cocatalyst
      of Fe3+. For the Ir:TiO2 photocatalyst, the two-step photoexcitation of an
      electron from the valence band to the conduction band through the Ir doping level
      occurred upon visible-light irradiation, as observed by electron spin resonance
      spectroscopy. The two-step photoexcitation through the doping level was found to
      be a more stable process with a lower recombination rate of hole-electron pairs
      than the two-step photoexcitation process through an oxygen vacancy. Once
      electrons are photoexcited to the conduction band by the two-step excitation, the
      electrons can easily transfer to the surface because the conduction band is a
      continuous electron path, whereas the electrons photoexcited at only the doping
      level could not easily transfer to the surface because of the discontinuity of
      this path. The observed two-step photoexcitation from the valence band to the
      conduction band through the doping level significantly contributes to the
      enhancement of the photocatalytic performance.

PMID- 28738680
TI  - Photothermal Effect Enhanced Cascade-Targeting Strategy for Improved Pancreatic
      Cancer Therapy by Gold Nanoshell@Mesoporous Silica Nanorod.
AB  - Pancreatic cancer, one of the leading causes of cancer-related mortality, is
      characterized by desmoplasia and hypovascular cancerous tissue, with a 5 year
      survival rate of <8%. To overcome the severe resistance of pancreatic cancer to
      conventional therapies, we synthesized gold nanoshell-coated rod-like mesoporous
      silica (GNRS) nanoparticles which integrated cascade tumor targeting (mediated by
      photothermal effect and molecular receptor binding) and photothermal treatment
      enhanced gemcitabine chemotherapy, under mild near-infrared laser irradiation
      condition. GNRS significantly improved gemcitabine penetration and accumulation
      in tumor tissues, thus destroying the dense stroma barrier of pancreatic cancer
      and reinforcing chemosensitivity in mice. Our current findings strongly support
      the notion that further development of this integrated plasmonic photothermal
      strategy may represent a promising translational nanoformulation for effective
      treatment of pancreatic cancer with integral cascade tumor targeting strategy and
      enhanced drug delivery efficacy.

PMID- 28738681
TI  - Optimizing High-Resolution Mass Spectrometry for the Identification of Low
      Abundance Post-Translational Modifications of Intact Proteins.
AB  - Intact protein analysis by liquid chromatography-mass spectrometry (LC-MS) is now
      possible due to the improved capabilities of mass spectrometers yielding greater
      resolution, mass accuracy, and extended mass ranges. Concurrent measurement of
      post-translational modifications (PTMs) during LC-MS of intact proteins is
      advantageous while monitoring critical proteoform status, such as for clinical
      samples or during production of reference materials. However, difficulties exist
      for PTM identification when the protein is large or contains multiple
      modification sites. In this work, analyses of low-abundance proteoforms of
      proteins of clinical or therapeutic interest, including C-reactive protein,
      vitamin D-binding protein, transferrin, and immunoglobulin G (NISTmAb), were
      performed on an Orbitrap Elite mass spectrometer. This work investigated the
      effect of various instrument parameters including source temperatures, in-source
      CID, microscan type and quantity, resolution, and automatic gain control on
      spectral quality. The signal-to-noise ratio was found to be a suitable spectral
      attribute which facilitated identification of low abundance PTMs. Source
      temperature and CID voltage were found to require specific optimization for each
      protein. This study identifies key instrumental parameters requiring optimization
      for improved detection of a variety of PTMs by LC-MS and establishes a
      methodological framework to ensure robust proteoform identifications, the first
      step in their ultimate quantification.

PMID- 28738682
TI  - Prototropically Allosteric Probe for Superbly Selective DNA Analysis.
AB  - Selective nucleotide recognition for biosensor evolution requires rational probe
      design toward the binding-pattern-susceptible readout but without serious poison
      in selectivity from the context sequences. In this work, we synthesized a dual
      function (trihydroxyphenyl)porphyrin (POH3) to target the abasic site (AP site)
      in ds-DNA using the trihydroxyphenyl substituent and the tetrapyrrole macrocycle
      as the recognition unit (RU) and the fluorescent signal unit (SU), respectively.
      RU and SU are separated from each other but are prototropically allosteric. We
      found that an appropriate pH favors formation of the nonfluorescent
      quinine/pyrrole (O-NH) conformer of POH3. However, the complementary hydrogen
      bonding of RU in O-NH with the target cytosine opposite the AP site switches on
      the SU fluorescence through prototropic allostery toward the phenol/isopyrrole
      (OH-N) conformer, while the bases thymine, guanine, and adenine totally silence
      this allostery, suggesting a superb selectivity in single-nucleotide polymorphism
      (SNP) analysis. The role of the prototropic allostery in achieving such SNP
      selectivity is also evidenced using porphyrins with other hydroxyl substituent
      patterns. Because of the SU separation from RU, SU is not directly involved in
      the interaction with the AP site, and thus, the turn-on selectivity is also
      realized for DNA with flanking guanine, the most easily oxidized base in DNA.
      This tolerance to the flanking base identity has seldom been achieved in previous
      studies. Additionally, other DNA structures cannot bring this allostery,
      indicating that the combination recipe of the AP site design and the
      prototropically allosteric probe will find wide applications in DNA-based
      sensors.

PMID- 28738683
TI  - State prescription drug monitoring programs and fatal drug overdoses.
AB  - OBJECTIVES: To examine the impact of prescription drug monitoring programs
      (PDMPs) on drug overdose deaths. STUDY DESIGN: We used variation in the timing of
      state PDMP legislation and implementation to estimate the impact of these
      programs on drug overdose mortality rates across all drug categories from 1999 to
      2014 and separately for each category from 1999 to 2010. Data used include US all
      jurisdiction mortality data, estimated population data, and sociodemographic data
      from the CDC and the US Census Bureau. METHODS: Multivariate regression models
      were applied to state panel data, including state and year fixed effects and
      state-specific linear time trends. Preprogram tests were used to assess the
      common trends assumption underlying our empirical approach. RESULTS: The
      implementation of PDMPs was not associated with reductions in overall drug
      overdose or prescription opioid overdose mortality rates relative to expected
      rates in the absence of PDMPs. For most categories, PDMPs were associated with
      increased mortality rates, but the associations were statistically insignificant.
      In a subsample analysis of states with PDMPs in operation for 5 or more years,
      the programs were found to be associated with significantly higher mortality
      rates in legal narcotics, illicit drugs, and other and unspecified drugs.
      CONCLUSIONS: PDMPs were not associated with reductions in drug overdose mortality
      rates and may be related to increased mortality from illicit drugs and other,
      unspecified drugs. More comprehensive and prevention-oriented approaches may be
      needed to effectively reduce drug overdose deaths and avoid fatal overdoses from
      other drugs used as substitutes for prescription opioids.

PMID- 28738684
TI  - Drivers of excess costs of opioid abuse among a commercially insured population.
AB  - OBJECTIVES: To replicate and extend a recently published analysis of the drivers
      of excess costs of opioid abuse. STUDY DESIGN: Retrospective data analysis using
      de-identified claims data from the Truven MarketScan Commercial Claims and
      Encounter database. METHODS: Medical and prescription drug claims from
      beneficiaries covered by large self-insured US companies were used to select
      patients with incident diagnoses of opioid abuse between 2012 and 2015. Two
      cohorts, abusers and nonabusers, were matched using propensity score methods.
      Excess healthcare costs were estimated over a 6-month baseline period and 12
      month follow-up period. Cost drivers were assessed by diagnosis (3-digit
      International Classification of Diseases, Ninth Revision, Clinical Modification
      groupings) and place of service. RESULTS: The analysis included 73,714 matched
      pairs of abusers and nonabusers. Relative to nonabusers, abusers had considerably
      higher annual healthcare costs of $10,989 per patient, or $1.98 per member per
      month. Excess costs were similar, yet lower, than the previous analysis using
      another commercial claims database. In both analyses, a ramp-up in excess costs
      was observed prior to the incident abuse diagnosis, followed by a decline post
      diagnosis, although not to baseline levels. Key drivers of excess costs in the 2
      studies included opioid use disorders, nonopioid substance misuse, and painful
      and mental health conditions. From 2010 to 2014, the prevalence of diagnosed
      opioid abuse doubled, with incidence rates exhibiting an increasing, though
      flatter, trend than earlier in the period. CONCLUSIONS: Opioid abuse imposes a
      considerable economic burden on payers. Many abusers have complex healthcare
      needs and may require care beyond that which is required to treat opioid abuse.
      These results are robust and consistent across different data sources.

PMID- 28738685
TI  - Assessing the effect of the VHA PCMH model on utilization patterns among veterans
      with PTSD.
AB  - OBJECTIVES: The Veterans Health Administration (VHA) implemented a patient
      centered medical home (PCMH)-based Patient Aligned Care Teams (PACT) model in
      2010. We examined its effects on the utilization of health services among US
      veterans with posttraumatic stress disorder (PTSD). STUDY DESIGN: We analyzed VHA
      clinical and administrative data to conduct an interrupted time series study.
      Encounter-level data were obtained for the period of April 1, 2005, through March
      31, 2014. We identified 642,660 veterans with PTSD who were assigned to either a
      high- or low-PCMH implementation group using a validated VHA PCMH measurement
      instrument. METHODS: We measured the effect of high-PCMH implementation on the
      count of hospitalizations and primary care, specialty care, specialty mental
      health, emergency department (ED), and urgent care encounters compared with low
      PCMH implementation. We fit a multilevel, mixed-effects, negative binomial
      regression model and estimated average marginal effects and incidence rate
      ratios. RESULTS: Compared with patients in low-PCMH implementation clinics,
      patients who received care in high-PCMH implementation clinics experienced a
      decrease in hospitalizations (incremental effect [IE], -0.036; 95% confidence
      interval [CI], -0.0371 to -0.0342), a decrease in specialty mental health
      encounters (IE, -0.009; 95% CI, -0.009 to -0.008), a decrease in urgent care
      encounters (IE, -0.210; 95% CI, -0.212 to -0.207), and a decrease in ED
      encounters (IE, -0.056; 95% CI, -0.057 to -0.054). CONCLUSIONS: High PCMH
      implementation positively affected utilization patterns by reducing downstream
      use of high-cost inpatient and specialty services. Future research should
      investigate whether a reduction in utilization of health services indeed results
      in higher levels of virtual and non-face-to-face access, or if the PACT model has
      reduced necessary access to care.

PMID- 28738686
TI  - Disparities in diabetes and hypertension care for individuals with serious mental
      illness.
AB  - OBJECTIVES: People with serious mental illnesses (SMI), including schizophrenia,
      bipolar disorder, and major depression, experience early mortality, partly due to
      comorbid physical health conditions such as diabetes and hypertension. This study
      examined the quality of diabetes and hypertension care for Medicaid and Medicare
      enrollees with SMI. STUDY DESIGN: We conducted a retrospective analysis of
      medical records and claims data from 3 health plans: a Medicaid plan for disabled
      adults, a Medicaid plan for low-income adults, and a Special Needs Plan for
      individuals dually enrolled in Medicaid and Medicare. The study population
      included 258 adults with SMI and diabetes and 241 adults with SMI and
      hypertension. METHODS: Existing quality measures for diabetes and hypertension
      from the Healthcare Effectiveness Data and Information Set (HEDIS) were adapted
      and applied to the SMI population for the 2012 calendar year. The rates of
      diabetes care and hypertension control for people with SMI were compared with
      national averages for Medicaid and Medicare managed care plans to examine
      disparities in care. RESULTS: Adults with SMI receive poor-quality care for
      diabetes and hypertension. Depending on the health plan, performance on the
      diabetes care and hypertension control HEDIS measures was 14 to 49 percentage
      points lower among the SMI population than the general Medicaid and Medicare
      populations. CONCLUSIONS: Findings highlight disparities in care for individuals
      with SMI compared with the general Medicaid and Medicare populations. Health
      plans demonstrated substantial room for improvement on almost all diabetes and
      hypertension HEDIS measures for the SMI population.

PMID- 28738687
TI  - Critical incident stress debriefing after adverse patient safety events.
AB  - Adverse events (AEs) are common, estimated to occur in around 10%
      internationally. Although preventable harm can be minimized, when AEs occur it is
      important that they be managed appropriately. AEs can be traumatic not only for
      patients, their friends, and relatives, but also for the involved clinicians, who
      have been referred to as "second victims" in a growing body of international
      research. Despite the frequency with which AEs occur, organizational mechanisms
      for supporting staff in these circumstances are not routinely embedded in
      healthcare settings. Critical Incident Stress Debriefing (CISD) has long been
      provided for professionals, such as disaster workers, who are exposed to
      traumatic and high-stress events. CISD is considered an effective strategy to
      promote resilience and recovery. We explore the potential value of providing CISD
      for health professionals involved in patient safety-related AEs and discuss the
      instances in which this could be routinely implemented.

PMID- 28738688
TI  - Improved correlation between animal and human potency of non-steroidal anti
      inflammatory drugs using quantitative structure-activity relationships (QSARs).
AB  - Animal models are known not to predict human responses well, in general. However,
      we have been able to demonstrate that, for a series of non-steroidal anti
      inflammatory drugs that are or were in clinical use, the incorporation of two
      simple physicochemical properties results in excellent correlations between human
      and rodent potencies for anti-inflammatory, analgesic and anti-pyretic
      activities. This has the potential to allow the use of historical data to improve
      drug development.

PMID- 28738689
TI  - Spermatozoa DNA and plasma membrane integrity after pellet optimized processing
      for cryopreservation in meat type chicken breeders.
AB  - 1. Aim of this study was the development of an optimised cryopreservation pellet
      procedure for chicken semen and the assessment of DNA and membrane integrity in
      frozen/thawed spermatozoa in a Hubbard F15 meat type selected strain. 2. The
      following semen processing conditions were studied: spermatozoa working
      concentration (SWC), 1.5 vs 2 * 109 cells/ml in pre-freezing extender;
      equilibration of diluted semen at 5 degrees C, 20 vs 40 min; dimethylacetamide
      concentration, 6% vs 9%; dimethylacetamide equilibration time at 5 degrees C, 1
      vs 30 min; thawing at 60 degrees C for 10 vs 50 degrees C for 30 sec. Spermatozoa
      viability (EtBr exclusion procedure - stress test), mobility (Accudenz(r) swim
      down test) and subjective motility were assessed in fresh and frozen-thawed
      semen. 3. The lower SWC (1.5 * 109 cells/ml) and the higher dimethylacetamide
      concentration (9%) had positive significant effects on the recovery rate of
      motile (22% vs 16%) and viable spermatozoa (39 vs 34%), respectively. 4.Membrane
      (SYBR14-PI staining) and DNA integrity (comet assay) were assessed before and
      after freezing/thawing according to the optimised protocol. 5. Recovery rates of
      spermatozoa with undamaged plasma membrane and DNA were 41% and 76%,
      respectively. The distribution of spermatozoa in classes of DNA damage was also
      analysed and discussed. 6. It was concluded that pellet cryopreservation was a
      damaging process mainly for plasma membrane rather than nuclear DNA in chicken
      spermatozoa.

PMID- 28738690
TI  - Magnetic resonance imaging in children presenting migraine with aura: Association
      of hypoperfusion detected by arterial spin labelling and vasospasm on MR
      angiography findings.
AB  - Objective A child presenting with a first attack of migraine with aura usually
      undergoes magnetic resonance imaging (MRI) to rule out stroke. The purpose of
      this study was to report vascular and brain perfusion findings in children
      suffering from migraine with aura on time-of-flight MR angiography (TOF-MRA) and
      MR perfusion imaging using arterial spin labelling (ASL). Methods We
      retrospectively included all children who had undergone an emergency MRI
      examination with ASL and TOF-MRA sequences for acute neurological deficit and
      were given a final diagnosis of migraine with aura. The ASL perfusion maps and
      TOF-MRA images were independently assessed by reviewers blinded to clinical data.
      A mean cerebral blood flow (CBF) value was obtained for each cerebral lobe after
      automatic data post-processing. Results Seventeen children were finally included.
      Hypoperfusion was identified in one or more cerebral lobes on ASL perfusion maps
      by visual assessment in 16/17 (94%) children. Vasospasm was noted within the
      intracranial vasculature on the TOF-MRA images in 12/17 (71%) children. All
      (100%) of the abnormal TOF-MRA images were associated with homolateral
      hypoperfusion. Mean CBF values were significantly lower ( P < 0.05) in visually
      hypoperfused lobes than in normally perfused lobes. Conclusion ASL and TOF-MRA
      are two totally non-invasive, easy-to-use MRI sequences for children in emergency
      settings. Hypoperfusion associated with homolateral vasospasm may suggest a
      diagnosis of migraine with aura.

PMID- 28738691
TI  - Selective cephalic upregulation of p-ERK, CamKII and p-CREB in response to
      glyceryl trinitrate infusion.
AB  - Background A common characteristic of migraine-inducing substances is that they
      cause headache and no pain in other areas of the body. Few studies have compared
      pain mechanisms in the trigeminal and spinal systems and, so far, no major
      differences have been noted. We compared signalling molecules in the trigeminal
      and spinothalamic system after infusion of the migraine-provoking substance
      glyceryltrinitrate. Method A catheter was placed in the femoral vein of rats and
      one week later glyceryltrinitrate 4 ug/kg/min was infused for 20 min. Protein
      expression in the dura mater, trigeminal ganglion, nucleus caudalis, dorsal root
      ganglion and the dorsal horn of the thoracic spinal cord was analysed at
      different time points using western blotting and immunohistochemistry. Results
      Glyceryltrinitrate caused a threefold increase in expression of phosphorylated
      extracellular signal-regulated kinases at 30 min in the dura mater and nucleus
      caudalis ( P < 0.05) and at 2 h in the trigeminal ganglion with very few
      expressions in the dorsal root ganglion. In the nucleus caudalis, expression of
      phosphorylated extracellular signal-regulated kinases and Cam KII increased 2.6
      fold and 3.2-fold, respectively, at 2 h after glycerytrinitrate infusion ( P <
      0.01). p-CREB/ATF-1 upregulation was observed only at 30 min ( P < 0.05) in the
      nucleus caudalis. None of these markers showed increased expression in the
      regions of thoracic spinal cord dorsal horn. Conclusion The dura, trigeminal
      ganglion and nucleus caudalis are activated shortly after glycerytrinitrate
      infusion with long-lasting expression of phosphorylated extracellular signal
      regulated kinases observed in the nucleus caudalis. These activations were not
      observed at the spinal level.

PMID- 28738692
TI  - Flavonoid profile, antioxidant and antiglycation properties of Retama
      sphaerocarpa fruits extracts.
AB  - Retama sphaerocarpa occurs in the Mediterranean area of North-east Africa and in
      the Iberian Peninsula, and grows on a variety of soil types and climatic
      conditions. Used in Algerian folk medicine, it is a valuable species for
      revegetation and soil restoration. The aim of this study is to evaluate flavonoid
      composition and antioxidant and antiglycation properties of methanolic and
      aqueous extracts from R. sphaerocarpa fruits. HPLC-PDA/ESI-MS was used to
      identify/quantify flavonoid content. Antioxidant activity was evaluated by Folin
      Ciocalteu, ORAC, FRAP, TEAC, and DPPH assays, and antiglycation capability by
      glucose/fructose-BSA assay. Results showed that fruits contain isoflavones
      (daidzein and genistein derivatives) and flavonols (apigenin, isorhamnetin,
      kaempferol and quercetin derivatives), and extracts (especially the methanolic
      one, richer in flavonoids) possess good in vitro antioxidant and antiglycation
      properties. These findings evidence that R. sphaerocarpa fruits are a source of
      valuable phytochemicals, with potential applications in the field of
      phytopharmaceuticals and in food industry.

PMID- 28738693
TI  - The accuracy of SpaceLabs 90207 in blood pressure monitoring in patients with
      atrial fibrillation.
AB  - PURPOSE: Irregular heart rhythm in the course of atrial fibrillation (AFib)
      results in lower blood pressure (BP) measurements reproducibility which is
      further limited by various BP-monitors used. Therefore the aim of our study was
      to estimate accuracy of oscillometric BP measurement (SpaceLabs 90207) with
      reference to mercury manometer-based readings. MATERIAL AND METHODS: Study was
      performed in 47 hemodynamically stable patients aged 63 +/- 12 yo with paroxysmal
      or persistent AFib, at baseline. Patients were reassessed within one week after
      effective cardioversion (SR; n = 29). BP was measured using Y-tube connection
      allowing for simultaneous measurements on the same arm with SpaceLabs 90207 and
      referral method. Mean values were tested with paired t-tests. Additionally,
      concordance correlation coefficient (rhoc) and Bland-Altman plots were assessed.
      Results were confronted with AAMI, and ESH-IP criteria. RESULTS: Both during
      arrhythmia and sinus rhythm diastolic BP differed significantly (Delta = 4.6 +/-
      6.0 mm Hg, p < .001 and 2.1 +/- 4.0 mm Hg, p < .001; for AFib, and SR,
      respectively), which was not the case for systolic BP. The rhoc during arrhythmia
      equaled 0.89, and 0.75 for systolic and diastolic BP, respectively, which further
      improved while SR (0.96 and 0.89, respectively). Results confronted against AAMI
      and ESH-IP showed that all criteria were met except for one (60% vs. required 65%
      of paired differences of less than 5 mm Hg) during AFib. CONCLUSIONS: The direct
      comparisons of BP readings allowed to conclude that diastolic blood pressure
      tended to be slightly overestimated when assessed with SpaceLabs 90207 in
      patients with both, AFib and SR, which was not a case for systolic BP. When the
      results were confronted with available validation protocols requirements, all
      referral criteria were met except for one. Taken together, our results suggest
      acceptable BP readings dispersion of SpaceLabs 90207 in BP monitoring of patients
      with both AFib and SR.

PMID- 28738694
TI  - Laccase: a green catalyst for the biosynthesis of poly-phenols.
AB  - Laccases (benzene diol: oxidoreductases, EC 1.10.3.2) are able to catalyze the
      oxidation of various compounds containing phenolic and aniline structures using
      dissolved oxygen in water. Laccase structural features and catalytic mechanisms
      focused on the polymerization of aromatic compounds are reported. A description
      about the most recent research on the biosynthesis of chemicals and polymers is
      made. Selected applications of this technology are considered as well as the
      advantages, shortcomings and future needs related with the use of laccases.

PMID- 28738695
TI  - A research on the genotoxicity of stevia in human lymphocytes.
AB  - Stevia extracts are obtained from Stevia rebaudiana commonly used as natural
      sweeteners. It is ~250-300 times sweeter than sucrose. Common use of stevia
      prompted us to investigate its genotoxicity in human peripheral blood
      lymphocytes. Stevia (active ingredient steviol glycoside) was dissolved in pure
      water. Dose selection was done using ADI (acceptable daily intake) value.
      Negative control (pure water), 1, 2, 4, 8 and 16 MUg/ml concentrations which were
      equivalent to ADI/4, ADI/2, ADI, ADI * 2 and ADI * 4 of Stevia were added to
      whole-blood culture. Two repetitive experiments were conducted. Our results
      showed that there was no significant difference in the induction of chromosomal
      aberrations and micronuclei between the groups treated with the concentrations of
      Stevia and the negative control at 24 and 48 h treatment periods. The data showed
      that stevia (active ingredient steviol glycosides) has no genotoxic activity in
      both test systems. Our results clearly supports previous findings.

PMID- 28738696
TI  - The role of autoantibodies in the syndromes of orthostatic intolerance: a
      systematic review.
AB  - Orthostatic intolerance is defined as the provocation of symptoms upon standing,
      commonly caused by neurogenic orthostatic hypotension (OH) and postural
      tachycardia syndrome (POTS), the etiology for which has not been fully uncovered
      yet. Many reports have described the occurrence of dysautonomia, orthostatic
      intolerance and POTS following febrile illness, presumably viral and post
      vaccine. Furthermore, patients with dysautonomia have higher rates of autoimmune
      disorders such as Hashimoto thyroiditis and SLE. Recent evidence has shown the
      presence of adrenergic and cholinergic receptor antibodies in patients with POTS
      and orthostatic hypotension. In patients with cholinergic receptor antibodies,
      higher titers correlate with the disease severity. Few reports have shown that
      immunomodulation therapy resulted in significant improvement in symptoms. In this
      article, we review the available literature correlating autoimmunity with
      orthostatic intolerance syndromes. Future studies are warranted to evaluate the
      prevalence of such antibodies and examine different treatment modalities in this
      sub group of patients.

PMID- 28738697
TI  - Reduction of heart rate variability in hypertensive elderly.
AB  - INTRODUCTION: The elderly population grows globally every day, and along with it
      the incidence of high blood pressure also grows, following these data scientists
      seek tools to improve the health of this population, a widely used tool for
      assessing cardiovascular function is the heart rate variability(HRV), that is a
      mecanism that allows the investigation of oscillations in the intervals between
      consecutive heart beats (RR intervals). There are already studies on the
      autonomic nervous system in the elderly population, however, these studies
      investigated normotensive patients and there is little research in hypertensive
      patients. AIM: To compare the cardiac autonomic modulation between healthy
      elderly and hypertensive elderly. METHOD: The total sample was 80 elderly people-
      40 healthy elderly and 40 elderly (HBP). Anthropometric data, HRV analysis and
      IPAQ questionnaire were collected. For the analysis of cardiac modulation data in
      the time domain (pNN50, SDNN and RMSSD) and frequency domain (LF and HF). The
      geometric analysis (RRtri, TINN, SD1, SD2 and SD1/SD2 ratios). RESULTS: In the
      time domain the MeanRR index presented a HAS increase 832.35 +/- 104.46 ms vs
      control 782.73 +/- 112.78 ms (p = 0.040). In the SDNN, there was a 58.35ms
      decrease vs the SAH 43.15 ms (p = 0.030). In the frequency domain, HF decreased
      control 247.00 ms2 vs HAS 157.00 ms2 (p = 0.002). In the geometric, the TINN and
      SD2 in the HAS group decreased in relation to the control from 203.38 +/- 80.26
      ms to 161.83 +/- 53.25 ms (p = 0.018) and from 71.95 ms to 59.40 ms (p = 0.051).
      The mean SD1/SD2 ratio showed an increase between the Control and SAH groups from
      0.22 +/- 0.10 to 4.09 +/- 1.18 and there was a statistical difference (p =
      0.001). CONCLUSION: Hypertensive elderly patients present decreased heart rate
      variability and decreased parasympathetic modulation when compared to
      normotensive elderly.

PMID- 28738698
TI  - Implementation and evaluation of a rehabilitation concept in a patient suffering
      from Scleredema Adultorum Buschke: a case report.
AB  - PURPOSE: Scleredema Adultorum Buschke is a disorder manifesting indurations of
      the skin mostly followed by musculoskeletal impairment. Data regarding this fact
      are seldom found and documentation of functional outcome of physical therapies
      and modalities related to Scleredema Adultorum Buschke is fragmentary. The aim of
      this case report is to demonstrate and to document an effective concept of
      rehabilitation in a patient suffering from Scleredema Adultorum Buschke. METHODS:
      A treatment plan was developed containing therapeutic ultrasound, manual
      lymphatic drainage, and physiotherapy. Assessments were performed at baseline and
      after therapy. RESULTS: Treatment by physical therapies of presented patient
      resulted in an improved functionality. Five out of eight Short Form-36
      questionaire sections increased in terms of enhanced general health and level of
      activity. CONCLUSIONS: Musculoskeletal impairment in a patient suffering from
      Scleredema Adultorum Buschke can be reduced by a multimodal concept of
      rehabilitation. Implications for Rehabilitation Rehabilitation professional
      should suspect scleredema in patients with diffuse skin thickening where hands
      and feet are spared Essential reactivating physical activity should be supported
      by skin softening physical modalities irrespective of etiology or primary
      therapy. There is a need for functional outcome measures and documentation in the
      rehabilitation of Scleredema Adultorum Buschke.

PMID- 28738699
TI  - Caspase-3 gene expression in human luteinized granulosa cells is inversely
      correlated with the number of oocytes retrieved after controlled ovarian
      stimulation.
AB  - Granulosa cells control oocyte maturation through paracrine signalling and
      changes to the microenvironment around the oocyte. Apoptosis occurs as a
      physiological mechanism of granulosa cell renewal, but how it relates with the
      ovarian response to induced ovulation is still unclear. Therefore, this study
      evaluated apoptosis-related gene expression levels in granulosa cells of patients
      undergoing controlled ovarian stimulation. We enrolled prospectively 59
      consecutive IVF patients referred to a tertiary academic hospital for couple
      infertility treatment. Luteinized granulosa cells were isolated from follicular
      fluid and the RNA was extracted, reverse-transcribed and the gene expression of
      apoptosis inducers (caspase-3, caspase-8 and bax) and inhibitor (Bcl-2) was
      quantified by real-time polymerase chain reaction. Caspase-3 gene expression
      correlated negatively with the number of pre-ovulatory follicles (Spearman's r = 
      -0.308), the number of collected oocytes (r =  -0.451), the number of mature
      oocytes (r =  -0.526), the number of fertilized oocytes (r =  -0.439) and the
      number of viable embryos (r =  -0.443, all statistically significant at p < 0.02
      level). No such associations were found with caspase-8, bax or bcl-2. These
      preliminary findings suggest that increased caspase-3 gene expression in
      granulosa cells is associated with a worse ovulatory response in humans.

PMID- 28738700
TI  - Cholecystokininoma syndrome, calcitonin and diarrhea.

PMID- 28738701
TI  - Association of the bitter taste receptor gene TAS2R38 (polymorphism RS713598)
      with sensory responsiveness, food preferences, biochemical parameters and body
      composition markers. A cross-sectional study in Italy.
AB  - This study examined the relationship between TAS2R38 gene polymorphism
      (RS713598), G/G, C/G or C/C genotype, and sensory responsiveness, food
      preferences, biochemical parameters and body composition in a cross-sectional
      study in 118 adults (24 men and 94 women). The frequencies of C/C, G/G and C/G
      were respectively 20.3%, 29.7% and 50.0%. As regards taste responsiveness,
      subjects with G-allele had a higher perception threshold than the C/C genotype
      for 6-n-propyl-2-thiouracil (PROP) (p < .05), and caffeine (p < .05). The G
      alleles had higher preferences for beer (OR: 6.25; p < .05), but lower for butter
      (OR: 0.64; p < .05) and cured meat (OR: 0.55; p < .05). Biochemical parameters
      and body composition markers did not differ between genotypes. Subjects with
      RS713598 polymorphism had a higher bitter taste perception threshold and higher
      or lower preferences for selected nutrient/energy dense foods, such as beer,
      butter and cured meat.

PMID- 28738702
TI  - Combined effects of whey protein hydrolysates and probiotics on oxidative stress
      induced by an iron-overloaded diet in rats.
AB  - Whey proteins possess antioxidant properties, and probiotics have various health
      promoting effects. We investigated the effects of whey protein hydrolysates
      (WPHs) and probiotics in rats exposed to oxidative stress induced by iron
      overload diet (IOL). Rats were divided into control (CTRL), IOL (0.2% ferrous
      sulphate), WPH (10%), probiotic (PB) mixture (Lactococcus lactis NK34 and B.
      polyfermenticus SCD), and WPH + PB group for 6 weeks. Average leukocytes and
      colonocytes tail moments were increased in IOL compared to CTRL but decreased in
      other groups. Conjugated diene was lower in WPH, PB, and WPH + PB than in IOL.
      Only WPH + PB group could recover glutathione S-transferase (GST) levels. SOD
      levels were recovered by WPH and PB. PB and WPH + PB increased alpha-tocopherol
      and only WPH + PB increased gamma-tocopherol. Thus, our data demonstrated that
      WPH and PB exhibit antioxidant properties in a rat model of high-iron diet
      induced oxidative stress and combination of them may provide an enhanced effect.

PMID- 28738703
TI  - Losses of nutrients and anti-nutrients in red and white sorghum cultivars after
      decorticating in optimised conditions.
AB  - The aims were to optimise pearling process of red and white sorghum by assessing
      the effects of pearling time and grain moisture on endosperm yield and flour ash
      content and to assess nutrient and anti-nutrient losses produced by pearling
      different cultivars in optimised conditions. Both variables significantly
      affected both responses. Losses of ashes (58%), proteins (9.5%), lipids (54.5%),
      Na (37%), Mg (48.5%) and phenolic compounds (43%) were similar among red and
      white hybrids. However, losses of P (30% vs. 51%), phytic acid (47% vs. 66%), Fe
      (22% vs. 55%), Zn (32% vs. 62%), Ca (60% vs. 66%), K (46% vs. 61%) and Cu (51%
      vs. 71%) were lower for red than white sorghum due to different degree of
      extraction and distribution of components in the grain. Optimised pearling
      conditions were extrapolated to other hybrids, indicating these criteria could be
      applied at industrial level to obtain refined flours with proper quality and good
      endosperm yields.

PMID- 28738704
TI  - Insights into the binding mode of sulphamates and sulphamides to hCA II:
      crystallographic studies and binding free energy calculations.
AB  - Sulphamate and sulphamide derivatives have been largely investigated as carbonic
      anhydrase inhibitors (CAIs) by means of different experimental techniques.
      However, the structural determinants responsible for their different binding mode
      to the enzyme active site were not clearly defined so far. In this paper, we
      report the X-ray crystal structure of hCA II in complex with a sulphamate
      inhibitor incorporating a nitroimidazole moiety. The comparison with the
      structure of hCA II in complex with its sulphamide analogue revealed that the two
      inhibitors adopt a completely different binding mode within the hCA II active
      site. Starting from these results, we performed a theoretical study on sulphamate
      and sulphamide derivatives, demonstrating that electrostatic interactions with
      residues within the enzyme active site play a key role in determining their
      binding conformation. These findings open new perspectives in the design of
      effective CAIs using the sulphamate and sulphamide zinc binding groups as lead
      compounds.

PMID- 28738706
TI  - Relationship between premature brain injury and multiple biomarkers in cord blood
      and amniotic fluid.
AB  - PURPOSE: The purpose of this study is to investigate the relationship between
      premature brain injury and multiple biomarkers in cord blood and amniotic fluid,
      identify potential biomarkers for early monitoring of premature brain injury.
      METHODS: One hundred and thirty cases of singleton premature infants with
      gestational age less than 34 weeks were evaluated. Based on brain imaging
      examination, all cases were divided into the brain injury group and the no brain
      injury group. Eleven biomarkers in cord blood and amniotic fluid were measured.
      RESULTS: Levels of interleukin-1beta (IL-1beta), IL-6, IL-8, tumor necrosis
      factor-alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), monocyte
      chemotactic protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM
      1), S100B, and activin A were higher in the brain injury group than those in the
      no brain injury group, in addition to S100B in amniotic fluid (p > .05), the
      differences were all statistically significant (p < .05). In the value of
      predicting brain injury, S100B had the highest sensitivity in cord blood, IL
      1beta had the highest sensitivity in amniotic fluid, and activin A owned the
      highest specificity both in cord blood and amniotic fluid. Levels of IL-4 and IL
      17A were too low and had no predictive value to brain injury. CONCLUSIONS: A
      variety of biomarkers in umbilical blood and amniotic fluid can predict preterm
      brain injury.

PMID- 28738705
TI  - New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of
      STAT3 and NF-kappaB transcription factors.
AB  - A set of new sulfurated drug hybrids, mainly derived from caffeic and ferulic
      acids and rosmaricine, has been synthesized and their ability to inhibit both
      STAT3 and NF-kappaB transcription factors have been evaluated. Results showed
      that most of the new hybrid compounds were able to strongly and selectively bind
      to STAT3, whereas the parent drugs were devoid of this ability at the tested
      concentrations. Some of them were also able to inhibit the NF-kappaB
      transcriptional activity in HCT-116 cell line and inhibited HCT-116 cell
      proliferation in vitro with IC50 in micromolar range, thus suggesting a potential
      anticancer activity. Taken together, our study described the identification of
      new derivatives with dual STAT3/NF-kappaB inhibitory activity, which may
      represent hit compounds for developing multi-target anticancer agents.

PMID- 28738707
TI  - Clinical evaluation of combined azacitidine and entinostat on the induction of
      fetal hemoglobin in patients with acute myeloid leukemias and myelodysplastic
      syndromes.

PMID- 28738708
TI  - The effect of hyoscine butylbromide on the duration and progress of labor in
      primigravidae: a randomized controlled trial.
AB  - OBJECTIVE: To assess the effect of hyoscine butylbromide (HBB) on duration of the
      first stage of labor in primigravdae. METHODS: A case-control study conducted on
      120 primigravida at term admitted in active labor were divided into three equal
      groups. A single dose of the drug (placebo or HBB 20 mg or HBB 40 mg) was
      injected intravenously slowly to groups A, B, and C. The duration of the first
      stage was calculated from the time of cervical dilatation of three to four
      centimeters in active labor until a fully dilated cervix was observed. RESULTS:
      The duration of first stage was significantly shorter in women receiving 20 and
      40 mg of HBB when controlled to control women (187.73 +/- 20.92, 186.41 +/- 19.40
      versus 231.39 +/- 33.14 min). There was no significant difference between the
      three study groups regarding duration of the second stage (36.76 +/- 9.98, 35.72
      +/- 9.97 and 37.55 +/- 10.57, respectively, p > .05), number of cases delivered
      by cesarean section (12.5%, 12.5%, and 15%, respectively, p > .05) and Apgar
      score of the neonates (p > .05). There was no significant difference between the
      three study groups regarding occurrence of side effects named dry mouth (7.5%,
      12.5%, and 5%, p > .05), flushing (2.5%, 5% and 0%, p > .05), tachycardia (2.5%,
      2.5%, and 2.5%, p > .05), or urinary retention (2.5%, 0%, and 0%, p > .05).
      CONCLUSION: Intravenous injection of HBB decreases the duration of active phase
      of labor in primigravidae with no side effects.

PMID- 28738709
TI  - Nebulized hypertonic saline to prevent ventilator associated pneumonia in
      premature infants, a randomized trial.
AB  - BACKGROUND/OBJECTIVES: Ventilator associated pneumonia (VAP) is a leading cause
      of death. Nebulized hypertonic saline solution (HSS) has been used to improve
      pulmonary clearance and reduce infection in intubated patients. This study
      examines whether nebulized HSS may reduce VAP in intubated premature infants.
      METHODS: We analyzed results of 100 intubated premature infants who completed the
      study. Infants were divided into: (a) the "Control" group, where VAP prevention
      protocol was implemented and (b) the "Intervention" group, where nebulized HSS
      twice daily was added to the package of care. Clinical, radiologic, and
      laboratory evidence of VAP, endotracheal aspirate and blood cultures, and days on
      mechanical ventilation were compared between groups. RESULTS: VAP occurred in 18%
      in the intervention group compared to 52% in the control group, relative risk
      0.35 (CI:0.18-0.66, p = .001). VAP incidence density was 16/1000 patient
      ventilator days in intervention group versus 30/1000 in control group. There was
      a significant reduction in the days of mechanical ventilation in the intervention
      group (10.7 +/- 8.6 and 16.9 +/- 3.4, p < .001). CONCLUSIONS: Nebulized HSS may
      help preserving lung clearance mechanisms and therefore reduce VAP in premature
      infants. Multi center, double blinded, randomized, controlled, trial is needed to
      confirm safety and efficacy of such intervention.

PMID- 28738711
TI  - Study comparing "Kangaroo Ward Care" with "Intermediate Intensive Care" for
      improving the growth outcome and cost effectiveness: randomized control trial.
AB  - AIMS: The aim of this study was to compare growth outcome and cost effectiveness
      of "Kangaroo ward care" (KWC) with "Intermediate intensive care" (IIC) in stable
      infants with birth weight 1000 g to <1100 g. MATERIAL AND METHODS: In this
      secondary analysis, we included 79 infants, with birth weight 1000 g to <1100 g.
      Thirty-eight were randomized to KWC and 41 to IIC group once the infant reached a
      weight of 1150 g. Infants in the KWC group were shifted to Kangaroo ward
      immediately after randomization and in the IIC group received IIC care till they
      attained a weight of 1250 g before shifting to Kangaroo Ward. After shifting to
      Kangaroo ward, infants in the IIC group received equivalent care to KWC group
      infants. RESULTS: There was significant better weight gain post-randomization
      during hospital stay and better length gain till 40 weeks of gestational age in
      intervention arm. There was reduction of post-randomization hospital stay by 2 d
      in the KWC group. The infants in the KWC group were shifted 6 d earlier to
      Kangaroo ward from IIC when compared with the IIC group. The cost-effective
      analysis that used "top-down" and "bottom-up" accounting method showed
      significant reduction of hospital and parents expenditure in the KWC group (p <
      .001) with saving of 570 USD per patient in the KWC group. CONCLUSION: Early
      shifting of infants to Kangaroo ward with birth weight 1000 g to <1100 g leads to
      better growth and is cost effective (CTRI/2014/05/004625). CLINICAL TRIAL
      REGISTRATION: Clinical trial registry of India CTRI/2014/05/004625.

PMID- 28738710
TI  - Use of traditional herbal medicine as an alternative in dental treatment in
      Mexican dentistry: a review.
AB  - CONTEXT: Herbal therapies are used worldwide to treat health conditions. In
      Mexico, generations have used them to treat gingivitis, periodontitis, mouth
      infections, and discoloured teeth. However, few studies have collected scientific
      evidence on their effects. OBJECTIVE: This study aimed at searching and compiling
      scientific evidence of alternative oral and dental treatments using medicinal
      herbs from Mexico. METHODS: We collected various Mexican medicinal plants used in
      the dental treatment from the database of the Institute of Biology at the
      National Autonomous University of Mexico. To correlate with existing scientific
      evidence, we used the PubMed database with the key term '(scientific name) and
      (oral or dental)'. RESULTS: Mexico has various medical herbs with antibacterial
      and antimicrobial properties, according to ancestral medicinal books and healers.
      Despite a paucity of experimental research demonstrating the antibacterial,
      antimicrobial, and antiplaque effects of these Mexican plants, they could still
      be useful as an alternative treatment of several periodontal diseases or as
      anticariogenic agents. However, the number of studies supporting their uses and
      effects remains insufficient. DISCUSSION AND CONCLUSION: It is important for the
      health of consumers to scientifically demonstrate the real effects of natural
      medicine, as well as clarify and establish their possible therapeutic
      applications. Through this bibliographical revision, we found papers that testify
      or refute their ancestral uses, and conclude that the use of plants to treat oral
      conditions or to add to the dental pharmacological arsenal should be based on
      experimental studies verifying their suitability for dental treatments.

PMID- 28738712
TI  - Diagnosis of human prostate carcinoma cancer stem cells enriched from DU145 cell
      lines changes with microscopic texture analysis in radiation and hyperthermia
      treatment using run-length matrix.
AB  - PURPOSE: Hyperthermia and radiation have the ability to induce structural and
      morphological changes on both macroscopic and microscopic level. Normal and
      damage cells have a different texture but may be perceived by human eye, as
      having the same texture. MATERIALS AND METHODS: To explore the potential of
      texture analysis based on run-length matrix, a total of 32 sphere images for each
      group and treatment regime were used in this study. Cells were subjected to the
      treatment with different doses of 6 MeV electron radiation (0 2, 4 and 6 Gy),
      hyperthermia (at 43 degrees  C in 0, 30, 60 and 90 min) and radiation +
      hyperthermia (at 43  degrees C in 30 min with 2, 4 and 6 Gy dose), respectively.
      Twenty run-length matrix (RLM) features were extracted as descriptors for each
      selected region of interest for texture analysis. Linear discriminant analysis
      was employed to transform raw data to lower-dimensional spaces and increase
      discriminative power. RESULTS: The features were classified by the first nearest
      neighbor classifier. RLM features represented the best performance with
      sensitivity, specificity, accuracy, positive predictive value (PPV) and negative
      predictive value (NPV) of 100% between 0 and 6 Gy radiation, 0 and 6 Gy radiation
      + hyperthermia, 0 and 90 min and 30 and 90 min hyperthermia groups. The area
      under receiver operating characteristic curve was 1 for these groups. CONCLUSION:
      RLM features have a high potential to characterize cell changes during different
      treatment regimes.

PMID- 28738713
TI  - Negative regulators of Wnt signaling pathway SFRP1 and SFRP3 expression in
      preterm and term pathologic placentas.
AB  - OBJECTIVE: Since Wnt signaling pathway plays a pivotal role in the placental
      development, we explored the expression of its negative regulators, SFRP1 and
      SFRP3 proteins in placentas from pathological pregnancies and compared their
      levels with those in healthy placentas. METHODS: Placentas (n = 79) were stained
      for SFRP1, and SFRP3 proteins by immunohistochemistry and their expression levels
      were quantified by stereological variable of volume density (Vv, mm degrees ).
      RESULTS: Significantly higher expressions of SFRP1 and SFRP3 were found in all
      investigated groups of term and preterm pathologic placentas as well as in
      preterm control placentas in comparison with normal-term placentas. CONCLUSIONS:
      Our findings indicate the active involvement of negative Wnt regulators
      SFRP1/SFRP3 in placental development and important role in pathology of
      pregnancy.

PMID- 28738714
TI  - A student-run mobile social platform enhanced the hidden-curriculum teaching.

PMID- 28738715
TI  - Antimicrobial, modulatory and chemical analysis of the oil of Croton limae.
AB  - CONTEXT: Croton sp. are plants with a well-reported antimicrobial activity.
      Croton limae A.P. Gomes, M.F. Sales P.E. Berry (Euphorbiaceae), known as
      'marmeleiro-prateado', is commonly used to manage abdominal pain in Brazil.
      OBJECTIVE: This work evaluates the phytochemical composition, antimicrobial and
      modulatory activities of the essential oil of C. limae leaves (EOCL). MATERIALS
      AND METHODS: The minimum inhibitory concentration (MIC) and the modulation of the
      antibiotic activity were determined using a microdilution method. The
      concentration of EOCL ranged between 512 and 8 MUg/mL. Staphylococcus aureus,
      Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Candida
      tropicalis, C. krusei and C. albicans strains were used in the MIC and modulation
      assays. The antibiotics, amikacin, gentamicin and neomycin, and the antifungals,
      amphotericin B, benzoylmetronidazole and nystatin, were used in concentrations
      ranging between 2500 and 2.5 MUg/mL. The phytochemical analysis of the EOCL was
      performed through gas chromatography coupled to a mass spectrometer (GC/MS).
      RESULTS: Only Staphylococcus aureus was inhibited by a clinically relevant
      concentration of EOCL (MIC 512 MUg/mL). Synergism between the EOCL and amikacin
      against S. aureus (9.76 MUg/mL) and E. coli (39.062 MUg/mL); neomycin against E.
      coli (2.44 MUg/mL); and benzoylmetronidazole against C. krusei (256 MUg/mL) were
      observed. The GC/MS analysis identified cedrol, eucalyptol and alpha-pinene as
      the main compounds of EOCL. CONCLUSION: EOCL inhibited the growth of S. aureus
      and potentiated the antibiotic and antifungal effects of drugs against all
      bacterial and Candida strains, respectively.

PMID- 28738716
TI  - The effect of obesity on early fetal growth and pregnancy duration: a cohort
      study.
AB  - OBJECTIVE: The objective of this study is to investigate the effect of maternal
      obesity on fetal size in first- and second-trimester pregnancies and to determine
      duration of pregnancy as estimated by a variety of methods. METHODS: Between 2006
      and 2011, a cohort study included (n = 9055) singleton pregnancies that resulted
      in live birth at Holbaek Hospital in Denmark. This study recorded first- and
      second-trimester fetal measurements and maternal anthropometry. Characteristics
      considered included mother's age, parity, height, body mass index (BMI), smoking
      habits, and sex of child. The correlation between BMI and duration of pregnancy
      was analyzed by time-to-event analysis and accounted for medical intervention by
      censoring while correlation of BMI on fetal size was evaluated by multiple
      regression analysis. RESULTS: Adjusting for maternal and fetal characteristics,
      BMI was associated with prolonged pregnancy duration (0.20-0.22 d per kg/m2
      (standard error (SE) 0.02)) when using ultrasound and 0.26 d per kg/m2 (SE: 0.03)
      when using last menstrual period. With increasing BMI, fetal biometries in first
      and second trimester were significantly smaller than expected (0.08 mm per kg/m2
      when measured by crown rump length (SE 0.02)). CONCLUSIONS: Maternal BMI is
      correlated to smaller fetal size in early pregnancy and prolongs duration of
      pregnancy.

PMID- 28738717
TI  - Optimization of simultaneous microwave/ultrasonic-assisted extraction of phenolic
      compounds from walnut flour using response surface methodology.
AB  - CONTEXT: Walnut is a traditional food as well as a traditional medicine recorded
      in the Chinese Pharmacopoeia; however, the large amounts of walnut flour (WF)
      generated in walnut oil production have not been well utilized. OBJECTIVE: This
      study maximized the total polyphenolic yield (TPY) from the walnut flour (WF) by
      optimizing simultaneous ultrasound/microwave-assisted hydroalcoholic extraction
      (SUMAE). MATERIALS AND METHODS: Response surface methodology was used to optimize
      the processing parameters for the TPY, including microwave power (20-140 W),
      ultrasonic power (75-525 W), extraction temperature (25-55  degrees C), and time
      (0.5-9.5 min). The polyphenol components were analysed by LC-MS. RESULTS: A
      second-order polynomial model satisfactorily fit the experimental TPY data (R2 =
      0.9932, P < 0.0001 and Radj2    = 0.9868). The optimized quick extraction
      conditions were microwave power 294.38 W, ultrasonic power 93.5 W, temperature
      43.38  degrees C and time 4.33 min, with a maximum TPY of 34.91 mg GAE/g, which
      was a rapid extraction. The major phenolic components in the WF extracts were
      glansreginin A, ellagic acid, and gallic acid with peak areas of 22.15%, 14.99%
      and 10.96%, respectively, which might be used as functional components for health
      food, cosmetics and medicines. DISCUSSION AND CONCLUSION: The results indicated
      that walnut flour, a waste product from the oil industry, was a rich source of
      polyphenolic compounds and thus could be used as a high-value functional food
      ingredient.

PMID- 28738718
TI  - Correlation between clinical fetal head station and sonographic angle of
      progression during the second stage of labor.
AB  - PURPOSE: To investigate the correlation between the angle of progression and the
      clinical fetal head station (FHS) during the second stage of labor, and to build
      reference range. MATERIALS AND METHODS: A prospective, observational study was
      conducted. Women carrying singleton term pregnancies were enrolled during the
      second stage of labor. FHS was assessed manually by a senior obstetrician, while
      the angle of progression (AOP) was assessed by transperineal ultrasound (TPU).
      Both examiners were blinded to each others results. The correlation between the
      sonographic AOP and the clinical FHS was analyzed. RESULTS: Seventy patients
      comprised the study group. Clinical FHS demonstrated an excellent correlation
      with the sonographic measurement of AOP (Pearson's Correlation 0.642, p < 0.001).
      This correlation was best described by a cubic regression according to the
      formula: 123.800 + 10.290 * FHS -2.889 * FHS +0.910, (r2 = 0.423, p < .001).
      After aggregation of the mean AOP per FHS, the relative predicted centiles values
      and standard deviation were calculated. The mean Z score between measured and
      predicted values of the AOP for a given FHS was 0.007 (range -0.13 to +0.006).
      CONCLUSIONS: Our results demonstrate a significant correlation between the
      clinical FHS and the TPU measured AOP. These standardized sonographic values may
      serve the obstetrician as a reliable, objective auxiliary tool for the evaluation
      of the FHS during the second stage of labor.

PMID- 28738719
TI  - Maternal serum glycodelin levels in preeclampsia and its relationship with the
      severity of the disease.
AB  - PURPOSE: Preeclampsia, in which insufficient trophoblastic invasion is thought to
      be one of the underlying mechanisms, is a common pregnancy disorder. Glycodelin
      is a regulator of immunosuppression, fertilization, implantation, and
      placentation. Because of its inhibitory effects on trophoblastic activity,
      trophoblast invasion is disturbed when its levels alter. We aimed to analyze
      serum glycodelin levels in preeclampsia and evaluate whether it correlates with
      the severity of disease. METHODS: This is a prospective case-control study
      conducted in a research and training hospital between March and September 2016.
      In this study, a total of 55 preeclamptic and 65 healthy pregnants were included.
      Preeclamptic patients were divided into two subgroups: 25 severe and 30 mild.
      Maternal serum glycodelin levels were measured using enzyme-linked immunosorbent
      assay. RESULTS: Glycodelin levels were higher in preeclamptic group as compared
      with controls (71.38 +/- 22.78 versus 42.32 +/- 12.28 ng/ml, p < .001). Also, it
      was higher in severe preeclampsia than the mild group (84.19 +/- 24.58 versus
      60.71 +/- 14.4 ng/ml, p < .001). Glycodelin was positively correlated with
      systolic and diastolic blood pressures (r = 0.637 and r = 0.714, respectively, p
      < .001), aspartate and alanine aminotransferases (r = 0.369, p = .006 and r =
      0.377, p = .005) and proteinuria (r = 0.342, p = .011). Moreover, it was
      correlated with birth weights and gestational age at delivery (r = -0.386, p =
      .004 and r = -0.394, p = .003, respectively). The role of glycodelin to diagnose
      preeclampsia was evaluated by receiver operating curve (ROC) curve. Area under
      the curve for glycodelin is 0.897 with p < .001. The sensitivity of glycodelin
      was 83.6% and the specificity was 80% at a threshold >53.64 ng/ml. Moreover, area
      under the curve for glycodelin to diagnose severe preeclampsia is 0.788 with p <
      .001. The sensitivity of glycodelin was 59% and the specificity was 93.3% at a
      threshold >83.97 ng/ml. CONCLUSION: Glycodelin may be a promising marker in
      predicting the presence and severity of preeclampsia.

PMID- 28738720
TI  - Association of SP-B gene 9306 A/G polymorphism (rs7316) and risk of RDS.
AB  - BACKGROUND: Respiratory distress syndrome (RDS) is a severe pulmonary disease
      predominantly affects preterm newborns. Polymorphisms of surfactant-protein genes
      have been mostly evaluated as the candidate contributors in genetics of RDS.
      However the results are divers in different studies. We aimed at investigating
      the association of surfactant protein B (SPB) gene 9306 A/G polymorphism (rs7316)
      with RDS development. METHOD: Three hundred and eighty newborns with gestational
      age of less than 34 weeks were included in a multicenter case-control study.
      Respiratory distress (RD) was scored according to Downes' scoring system.
      Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method was used for genotyping. RESULT: One hundred and eighty-four neonates
      showed RDS and 196 did not. Gestational age (GA) was significantly lower in the
      RDS group compared with the controls. AA genotype and A allele were found more
      frequently in the RDS group than the controls (96.2% versus 63.8% and 98.1%
      versus 80.6%, respectively) (p =.0001). CONCLUSIONS: This is the first report of
      association of SFTPB rs7316 polymorphism with RDS development in Iranian
      newborns. The current study suggests that GA <28-weeks is the most important
      factor in predisposition to RDS. Genetic background in terms of SP-B gene might
      be involved in predisposition to RDS in premature neonates.

PMID- 28738721
TI  - The clinical value of maternal and fetal Doppler parameters in low-risk postdates
      pregnancies - a prospective study.
AB  - OBJECTIVE: The objective of this study is to determine the clinical significance
      of maternal and fetal ultrasound Doppler flow indices in postdates pregnancies.
      METHODS: This prospective study comprised 120 low-risk pregnant women beyond 40
      weeks of gestation. All participants underwent Doppler assessment including of
      fetal middle cerebral artery (MCA), umbilical, and uterine arteries. Perinatal
      outcomes were recorded and evaluated for possible associations with Doppler flow
      values. Adverse perinatal outcomes were defined as umbilical cord arterial pH
      <7.1, Apgar score <7 at 5 min, neonatal admission to a neonatal intensive care
      unit, and emergency cesarean section due to abnormal intrapartum cardiotocogram
      Results: Adverse perinatal outcome rate was 17.5% (n = 21). Doppler indices of
      umbilical artery, MCA, uterine artery and the cerebroplacental ratio (CPR) did
      not differ significantly between pregnant women with and without adverse
      perinatal outcomes. Neonatal birth weight was found to correlate negatively with
      umbilical artery Doppler indices, including the peak systolic to end diastolic
      ratio (p = .04), the resistance index (p = .02), and the pulsatility index (p =
      .01). Doppler values of the uterine artery, MCA and CPR did not correlate with
      neonatal birth weight. CONCLUSIONS: The contribution of maternal and fetal
      ultrasound Doppler to the prediction of adverse perinatal outcomes in low-risk
      postdates pregnancies is low. Hence, performing routine Doppler examination as
      part of postdates pregnancy assessments is unlikely to yield significant clinical
      benefit.

PMID- 28738723
TI  - Patients' expectations for the functional and psychosocial outcomes of orbital
      decompression surgery for thyroid eye disease: a qualitative study.
AB  - Patients with appearance-altering conditions may be dissatisfied with the
      outcomes of reconstructive surgery due to unmet expectations. This study explored
      patients' expectations of orbital decompression surgery for thyroid eye disease
      (TED) and whether these were met. Semi-structured interviews were conducted at
      two times: (1) in the weeks after patients were listed for decompression surgery
      and before surgery; (2) up to 12 months after surgery. Thematic analysis was
      performed for each time point, to identify themes within the data. Fourteen
      adults with TED were interviewed prior to surgery and five were followed up after
      surgery. Thematic analyses found: (1) Prior to surgery, patients had formed
      expectations through online information about the procedure, consultations with
      physicians, the impact TED had on their lives, and speaking to relevant others.
      Patients had specific expectations about the procedure, the recovery, post
      operative appearance and post-operative vision. (2) After surgery, patients
      generally felt their appearance and well-being had improved. However,
      dissatisfaction was linked to unanticipated specific aspects of surgical care,
      recovery, or appearance. Dissatisfaction can arise from unmet expectations for
      the outcomes of reconstructive surgery. Physicians should be aware of the
      processes by which patients form expectations, for example different types and
      quality of online information. Ensuring that preoperative expectations are
      realistic could enhance satisfaction after surgery.

PMID- 28738722
TI  - Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and
      BAX/ERCC1 gene expression.
AB  - CONTEXT: Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth
      produce compounds, such as isatin (ISA) and indirubin (IRN), which possess
      antitumour properties. Their effects in mammalian cells are still not very well
      understood. OBJECTIVE: We evaluated the activities of ISA and/or IRN on cell
      viability and apoptosis in vitro, their genotoxic potentials in vitro and in
      vivo, and the IRN- and ISA-induced expression of ERCC1 or BAX genes. MATERIALS
      AND METHODS: HeLa and/or CHO-K1 cell lines were tested (3 or 24 h) in the MTT,
      Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked
      micronucleus (CBMN) and comet (36, 24 and 72 h) tests after treatment with IRN
      (0.1 to 200 MUM) or ISA (0.5 to 50 MUM). Gene expression was measured by RT-qPCR
      in HeLa cells. Swiss albino mice received IRN (3, 4 or 24 h) by gavage (50, 100
      and 150 mg/kg determined from the LD50 - 1 g/kg b.w.) and submitted to comet
      assay in vivo. RESULTS: IRN reduced the viability of CHO-K1 (24 h; 5 to 200 MUM)
      and HeLa cells (10 to 200 MUM), and was antiproliferative in the CBMN test (CHO
      K1: 0.5 to 10 MUM; HeLa: 5 and 10 MUM). The drug did not induce apoptosis,
      micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa
      cells (3 and 24 h) at all doses tested. IRN (100 and 150 mg/kg) also induced
      genotoxicity in vivo (4 h). CONCLUSION: IRN and ISA have properties that make
      them candidates as chemotherapeutics for further pharmacological investigations.

PMID- 28738724
TI  - Neighbor effect: penumbra-dose exposed neighbor cells contribute to the enhanced
      survival of high-dose targeted cells.
AB  - PURPOSE: In the last decade, new types of 'bystander effect' have been suggested
      by multiple research groups and have been challenged by others. In this study, we
      explored a new type of bystander effect, which has been defined in previous
      studies as the enhancement of the survival of high-dose targeted cells due to the
      penumbra-dose exposed neighbor cells. Intensity-modulated radiation therapy,
      which is the most widely used treatment modality, generates local regions of
      gradient doses between targeted and shielded cells throughout the treatment
      volume; therefore, we were urged to ascertain whether the new type of effect is
      real and to suggest a revised treatment planning. MATERIALS AND METHODS: Cellular
      responses under non-uniform beam fields were observed in rat gliosarcoma cells,
      rat diencephalon cells, and mouse endothelial cells. The cells were irradiated
      with 200 kVp X-rays in two types: (1) all the cells in the flask were exposed to
      the X-ray beam (whole-beam exposure) and (2) half of the cells in the flask were
      exposed to the beam while the other half, or neighbor cells, were shielded from
      the beam (half-beam exposure). Target cells were exposed to 1, 2, 4, 6, 8, and 10
      Gy, and the penumbra dose was approximately 10%-20% of the target dose. RESULTS:
      Target cells survived high-dose (> 6 Gy) radiation exposures better under half
      beam exposure with the low penumbra-dose exposed neighbor cells around than under
      whole-beam exposure. The survival of the targeted cells from half-beam exposure
      was reduced when the radiation self-conditioned medium was replaced with a fresh
      one immediately after irradiation. Survival was further reduced when the targeted
      cells were harvested immediately after irradiation and incubated in new dishes
      with fresh culture media until the colony was counted. CONCLUSION: We have
      collected data of good statistics by several post-irradiation treatments of
      targeted cells to ascertain that the new type of bystander effect is real. The
      low penumbra-dose exposed neighbor cells benefited the survival of the high-dose
      targeted cells.

PMID- 28738725
TI  - Seeding nerve sutures with minced nerve-graft (MINE-G): a simple method to
      improve nerve regeneration in rats.
AB  - BACKGROUND: The aim of this study was to assess the effect of seeding the distal
      nerve suture with nerve fragments in rats. METHODS: On 20 rats, a 15 mm sciatic
      nerve defect was reconstructed with a nerve autograft. In the Study Group (10
      rats), a minced 1 mm nerve segment was seeded around the nerve suture. In the
      Control Group (10 rats), a nerve graft alone was used. At 4 and 12 weeks, a
      walking track analysis with open field test (WTA), hystomorphometry (number of
      myelinated fibers (n), fiber density (FD) and fiber area (FA) and soleus and
      gastrocnemius muscle weight ratios (MWR) were evaluated. The Student t-test was
      used for statistical analysis. RESULTS: At 4 and 12 weeks the Study Group had a
      significantly higher n and FD (p = .043 and .033). The SMWR was significantly
      higher in the Study Group at 12 weeks (p = .0207). CONCLUSIONS: Seeding the
      distal nerve suture with nerve fragments increases the number of myelinated
      fibers, the FD and the SMWR. The technique seems promising and deserves further
      investigation to clarify the mechanisms involved and its functional effects.

PMID- 28738726
TI  - Weighing obligations to home care workers and Medicaid recipients.
AB  - In June 2016, a US Department of Labor rule extending minimum wage and overtime
      pay protections to home care workers such as certified nursing assistants and
      home health aides survived its final legal challenge and became effective.
      However, Medicaid officials in certain states reported that during the
      intervening decades when these protections were not in place, their states had
      developed a range of innovative services and programs providing home care to
      people with disabilities-services and programs that would be at risk if workers
      were newly owed minimum wage and overtime pay. In this article, we examine
      whether the Department of Labor was right to extend these wage protections to
      home care workers even at the risk of a reduction in these home care services to
      people with disabilities. We argue that it was right to do so. Home care workers
      are entitled to these protections, and, although it is permissible under certain
      conditions for government to infringe workers' occupational rights and
      entitlements, these conditions are not satisfied in this case.

PMID- 28738727
TI  - The home as ethos of caring: A concept determination.
AB  - BACKGROUND: Within nursing, the concepts of home and homelike have been used
      indiscriminately to describe characteristics of healthcare settings that resemble
      a home more than an institution. OBJECTIVES: The aim of this study was to
      investigate the concept of home ( hem in Swedish). The main questions were as
      follows: What does the concept of home entail etymologically and semantically? Of
      what significance is the meaning of the concept to caring science and nursing?
      DESIGN AND METHODS: This study had a qualitative design with a hermeneutical
      approach guided by Gadamer. Eriksson's model of concept determination was partly
      used to determine the etymology and semantics, the essence and epistemic category
      of the concept of home. In this study, etymological dictionaries and 17 Swedish
      language dictionaries published between 1850 and 2001 were investigated. Ethical
      consideration: In all parts of this study, ethical guidelines have been followed
      concerning both gathering data from dictionaries and other sources and during the
      interpretation of these sources. FINDINGS: The home, framed as the ethos of
      caring, can be drawn as a three-dimensional picture where the three dimensions
      have a common core, enclosed and inviolable. Symbolically, the picture of home
      can be seen as the ethos of the human being's innermost room, the human being's
      manner of being and the tone expressed in the external or abstract room where the
      human being lives and interacts with others. CONCLUSION: Based on the findings in
      this study, we conclude that home as ethos is an inner ethical dimension within
      the human being. Human beings who are in contact with their ethos, the self, feel
      at home and dare to follow the voice of their heart. Nurses who experience at
      homeness have an ability to invite the patient into a caring relationship. The
      home and the feeling of being at home have significant meaning in terms of human
      beings' health and well-being.

PMID- 28738728
TI  - Job task characteristics of Australian emergency services volunteers during
      search and rescue operations.
AB  - Search and rescue operations are necessary in locating, assisting and recovering
      individuals lost or in distress. In Australia, land-based search and rescue roles
      require a range of physically demanding tasks undertaken in dynamic and
      challenging environments. The aim of the current research was to identify and
      characterise the physically demanding tasks inherent to search and rescue
      operation personnel within Australia. These aims were met through a subjective
      job task analysis approach. In total, 11 criterion tasks were identified by
      personnel. These tasks were the most physically demanding, frequently occurring
      and operationally important tasks to these specialist roles. Muscular strength
      was the dominant fitness component for 7 of the 11 tasks. In addition to the
      discrete criterion tasks, an operational scenario was established. With the tasks
      and operational scenario identified, objective task analysis procedures can be
      undertaken so that practitioners can implement evidence-based strategies, such as
      physical selection procedures and task-based physical training programs,
      commensurate with the physical demands of search and rescue job roles.
      Practitioner Summary: The identification of physically demanding tasks amongst
      specialist emergency service roles predicates health and safety strategies which
      can be incorporated into organisations. Knowledge of physical task parameters
      allows employers to mitigate injury risk through the implementation of strategies
      modelled on the precise physical demands of the role.

PMID- 28738729
TI  - Utility of a laboratory score in the prediction of gastric emptying in autoimmune
      gastritis patients.
AB  - OBJECTIVES: Patients with autoimmune gastritis may have symptoms suggestive of
      delayed gastric emptying. The aim of this study was to explore the predictive
      value of two scoring systems in the differentiation of delayed gastric emptying
      in patients with autoimmune gastritis. METHODS: About 154 patients (106 women)
      with autoimmune gastritis whose gastric emptying test were available, were
      analyzed using two laboratory-based scoring systems: 'global score' (hemoglobin,
      mean corpuscular volume, gastrin, vitamin B12, and chromogranin A) and 'simple
      score' (hemoglobin, mean corpuscular volume, and gastrin) in order to
      discriminate delayed and normal gastric emptying. RESULTS: The mean 'simple
      score' was 4.82 +/- 0.94 for autoimmune gastritis patients with delayed gastric
      emptying and 0.72 +/- 0.60 for patients with normal gastric emptying (p < 0.001).
      The mean 'global score' was 7.42 +/- 0.81 for autoimmune gastritis patients with
      delayed gastric emptying and 1.176 +/- 0.98 (p < 0.001) for patients with normal
      gastric emptying. There was also a positive correlation between severity of
      symptoms of patients with autoimmune gastritis and global (r = 0.83, p < 0.001)
      and simple scores (r = 0.81, p < 0.001). CONCLUSION: This model may help
      physicians, while evaluating autoimmune gastritis patients and deciding which
      patients need gastric emptying test. Gastric emptying study should be ordered in
      patients who are fulfilling the criteria proposed by these scoring systems.

PMID- 28738730
TI  - Male urethral reconstruction using vagina as a substitute in a 45X/46XY case.

PMID- 28738731
TI  - Grandchildren's Depressive Symptoms and Perceptions of Family Functioning:
      Protective and Influencing Factors.
AB  - A recent increase in children living with grandparents places more children at
      increased risk for emotional, psychological, or behavioral problems. This study
      used the Resiliency Model of Family Stress, Adjustment, and Adaptation to examine
      how children's living situation, parental monitoring, child's resourcefulness,
      and perceived support affect depressive symptoms and perceived family
      functioning. Of participants, 36% ( n = 56) lived with their parents only, 44% (
      n = 69) lived with a grandmother as their primary caregiver, and 20% ( n = 31)
      lived in a multigenerational household. Results indicate parental monitoring and
      support affected perceptions of family functioning. Subjective support and
      resourcefulness affected depressive symptoms. No effects were found from living
      situation and demographic factors. Resourcefulness had the strongest effect on
      depressive symptoms, with a 3-point decrease in symptoms for each incremental
      increase in resourcefulness. This study provides insight into factors influencing
      children's depressive symptoms and perceived family functioning, and provides
      direction for the development of future interventions.

PMID- 28738732
TI  - Comparative evaluation of physical characteristics of different inflatable penile
      prostheses.
AB  - OBJECTIVE: The aim of this study was to describe and evaluate existing inflatable
      penile prostheses (IPPs) in an independent laboratory setting. MATERIALS AND
      METHODS: New IPPs were obtained from two manufacturers: American Medical Systems
      (AMS) and Coloplast. The AMS 700TM LGX (18 cm), CX (18 cm) and CXR (14 cm), and
      the Coloplast Titan(r) Touch (18 cm) and Titan Narrow (14 cm) were investigated.
      Internal pressure, length and girth of the cylinders were measured at 2 ml
      increments. A urodynamic individual transducer connected to an analogue amplifier
      and recording system was used to measure pressure. Rigidity and axial loading of
      the different IPPs were evaluated with a compression system. RESULTS: Regular
      size prostheses were inflated to 22 ml and narrow prostheses to 16 ml. The Titan
      Touch had a girth of 17.8 mm at 22 ml compared to 15.6 mm for the AMS 700 LGX and
      16.5 mm for CX. The AMS 700 LGX increased in length by 13 mm from baseline, a
      feature that was unique among all the tested prostheses. Rigidity curves as
      assessed by compression showed significant variability, with both Titan
      prostheses and the AMS CXR exhibiting similar patterns and requiring a higher
      load to reach 50% compression. The buckling experiment showed different patterns
      of deformity. CONCLUSIONS: The results suggest that these prostheses exhibit
      significant physical differences. The clinical impact of these differences is
      poorly elucidated. These variations in behavior of the prostheses could be
      considered by physicians and patients when objectively assessing the choice of
      prosthesis. These findings could aid in objective patient counseling.

PMID- 28738733
TI  - Cases of mortality in little penguins (Eudyptula minor) in New Zealand associated
      with avian malaria.
AB  - CASE HISTORY A little penguin (Eudyptula minor) of wild origin, in captivity at
      Wellington Zoo, became inappetent and lethargic in March 2013. Despite supportive
      care in the zoo's wildlife hospital, the bird died within 24 hours. CLINICAL
      FINDINGS Weight loss, dehydration, pale mucous membranes, weakness, increased
      respiratory effort and biliverdinuria were apparent on physical examination.
      Microscopic evaluation of blood smears revealed intra-erythrocytic stages of
      Plasmodium spp. and a regenerative reticulocytosis in the absence of anaemia.
      PATHOLOGICAL FINDINGS Post-mortem findings included reduced body condition,
      dehydration, pulmonary congestion and oedema, hepatomegaly, splenomegaly,
      hydropericardium and subcutaneous oedema. Histopathological findings included
      protozoal organisms in sections of lung, liver and spleen. A marked, diffuse, sub
      acute interstitial histiocytic pneumonia was present. Accumulation of
      haemosiderin was noted in the Kupffer cells of the liver and in histiocytic-type
      cells in the spleen. MOLECULAR TESTING DNA was extracted from frozen portions of
      the liver. Nested PCR results and DNA sequencing confirmed infection of the
      deceased little penguin with Plasmodium (Huffia) elongatum lineage GRW06.
      DIAGNOSIS Avian malaria due to Plasmodium (Huffia) elongatum GRW06 RETROSPECTIVE
      INVESTIGATION A retrospective analysis of 294 little penguin cases in the Massey
      University post-mortem database revealed three other potential avian malaria
      cases. Analysis of archived tissues using a nested PCR for Plasmodium spp.
      followed by DNA sequencing revealed that a little penguin which died at Auckland
      Zoo was infected with P. elongatum GRW06 and two wild little penguins found dead
      on New Zealand beaches were infected with P. relictum SGS1 and Plasmodium. sp.
      lineage LINN1. Therefore, the overall frequency of deaths in little penguins
      associated with avian malaria was 4/295 (1.36%). CLINICAL RELEVANCE Our results
      suggest that avian malaria is associated with sporadic mortality in New Zealand's
      little penguins both in the wild and in captivity, but there is no evidence of
      mass mortality events due to Plasmodium spp. infection.

PMID- 28738734
TI  - A tissue factor-cascade-targeted nanoparticle forsite-directed inducing
      thrombosis.
AB  - Tissue factor is an upstream component of the cascade and a high-expressing
      factor under phathological conditions. In this study, a tissue factor cascade
      targeted strategy for inducing local thrombosis was developed by combining ENP
      HMME and photochemistry. In vitro study showed that protein EGFP-EGF1 conjugation
      to the nanoparticles could significantly contribute to the uptake of
      nanoparticles by tissue factor over-expressed brain capillary endothelial cells.
      Three-dimensional imaging and specklegram of brains in vivo showed that tissue
      factor cascade-targeted strategy successfully induced thrombosis of expected
      position. As shown by the in vivo multispectral fluorescent imaging, when ENP
      HMME was combined with photochemistry, higher accumulation in the infarction
      hemisphere was observed, which might suggest that the photochemistry inducing
      tissue factor cascade recruited more ENP-HMME than HMME-loaded nanoparticles (NP
      HMME). The data indicated the tissue factor cascade-targeted strategy has
      potential to induce local thrombosis, and might be applied in the treatment of a
      variety of hypervascular diseases.

PMID- 28738735
TI  - Clinician perspectives on cross-education in stroke rehabilitation.
AB  - PURPOSE: Cross-education is a neural phenomenon where strength of an untrained
      muscle improves after unilateral training of the opposite homologous muscle. It
      has been extensively studied in healthy populations and shows promise for post
      stroke rehabilitation. The purpose of this study is to understand current post
      stroke upper extremity rehabilitation practice; clinician's perspectives on cross
      education and; facilitators and barriers to implementation of a cross-education
      intervention. MATERIALS AND METHODS: This qualitative study used an interpretive
      description framework. Twenty-three occupational therapists and two
      physiotherapists who worked with individuals with stroke were interviewed.
      Digital audio files were transcribed and then line-by-line coding for units of
      information was conducted by two investigators. A third investigator, who was not
      present during the interviews, participated in category development. RESULTS AND
      CONCLUSIONS: Cross-education is paradoxical yet promising was the primary theme.
      This theme was elucidated by three descriptive categories: (1) therapists worked
      in a forced-use paradigm; (2) there was gap in current practice for those with
      more severe impairments in arm function; and (3) cross-education used as an
      adjunct could be useful within current practice for specific patients. Therapists
      suggested that educational materials for clinicians, patients, and patient
      families would be essential to the success of cross-education to explain training
      the less affected limb. This study provides important foundational information
      about clinician perspectives that will facilitate future translational research
      in this area. Implications for rehabilitation Cross education, or training the
      stronger arm to increase strength in the weaker arm, is an intervention
      particularly appropriate for people with stroke who have severe impairments in
      arm strength. This intervention should not replace the forced use paradigm, but
      may be a useful adjunct in rehabilitation. Therapists perceived that education of
      patients, families, therapists, and doctors would be critical for cross education
      to be implemented successfully - as it is opposite the forced use paradigm that
      characterizes most of stroke rehabilitation.

PMID- 28738736
TI  - Bacterial vaginosis and the risk of early miscarriage in women undergoing
      intracytoplasmic sperm injection cycles: a prospective cohort study.
AB  - This study aimed to assess the possible association of bacterial vaginosis (BV)
      and early miscarriage in 408 women undergoing intracytoplasmic sperm injection
      (ICSI) for reasons of male infertility. A vaginal sample was obtained before
      oocyte retrieval and evaluated for BV-associated bacteria using the Nugent
      scoring system. The primary outcome was early miscarriage and the secondary
      outcomes included implantation, pregnancy, late miscarriage, preterm delivery and
      live birth rates. Chi-square, ANOVA, relative risk and odds ratio were used for
      data analysis where appropriate. The prevalence of BV was estimated as 7.3%. From
      336 patients who had embryo transfer, 138 patients (41.1%) conceived. A total of
      17% (n = 23) of pregnant women miscarried during the first trimester: 15 patients
      (15%) were normal, 4 (17.4%) were intermediate and 4 (26.7%) patients had BV (p =
      0.52). The relative risk of early miscarriage in BV patients compared to the non
      BV and intermediate group was 1.77 (0.68-4.64, 95% CI). Implantation, pregnancy,
      preterm delivery and live birth rates were comparable between groups. We conclude
      that BV does not appear to have an adverse impact on outcomes in women being
      treated with ICSI for male factor infertility and is not associated with
      miscarriage and preterm birth.

PMID- 28738737
TI  - 20/20 Hindsight: A 25-year programme at the Anna Freud Centre of efficacy and
      effectiveness research on child psychoanalytic psychotherapy.
AB  - OBJECTIVE: This paper describes the evolution of methods of enquiry-through 25
      years of work, with Professor Peter Fonagy and many other colleagues-of research
      and theorizing about child and adolescent therapy outcomes. METHOD: The work has
      focused on measuring psychoanalytic outcomes, but with an increasing interest in
      discovering therapeutic elements across treatment modalities. RESULTS: Headline
      findings are described, with lessons from the ups and downs of developing (a)
      retrospective, follow-up, and prospective outcome studies, and (b) measures of
      child and family functioning. Issues of manualizing and measuring treatment
      process are discussed, together with the fruitfulness of mixed-method
      (quantitative and qualitative) process and outcome research with young people and
      families. CONCLUSIONS: Using the dilemmas, experiences, and findings ??of our
      group as examples, growing points and well as growing pains for the field are
      suggested.

PMID- 28738738
TI  - A pilot study comparing the effect of orally administered esomeprazole and
      omeprazole on gastric fluid pH in horses.
AB  - AIMS To compare the efficacy of an enteric coated esomeprazole paste with an
      enteric coated omeprazole paste to increase gastric pH after oral administration
      in horses. METHODS Nine adult Standardbred horses were randomly assigned to three
      groups, each containing three horses, for a study comprising three phases of 10
      days, with an 18-day washout period between each phase. In each phase, three
      horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo,
      as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all
      horses received all three treatments. Gastric fluid samples were collected using
      a gastroscope on Days 1, 3, 5, 8 and 10, with food and water withheld for 16
      hours prior to collection of samples. The pH of all samples was measured
      immediately after collection. RESULTS Mean pH (3.38; SD 1.75) of the gastric
      fluid samples in the horses that received the placebo was lower than in the
      horses that received esomeprazole (6.28; SD 1.75) or omeprazole (6.13; SD 1.75)
      (p<0.001). There was no difference in the mean pH between horses receiving
      esomeprazole and those receiving omeprazole (p=0.56). CONCLUSIONS AND CLINICAL
      RELEVANCE Under these study conditions, esomeprazole paste was equally as
      effective as omeprazole paste in increasing gastric pH in horses. Enteric coated
      esomeprazole, may be a therapeutic alternative to omeprazole for the prevention
      of gastric ulcers in horses.

PMID- 28738739
TI  - Review of outcomes and measurement instruments in cochlear implantation studies.

PMID- 28738741
TI  - Human biology of migration.

PMID- 28738740
TI  - A systematic review of the effectiveness of task-specific rehabilitation
      interventions for improving independent sitting and standing function in spinal
      cord injury.
AB  - CONTEXT: Impaired balance function after a spinal cord injury (SCI) hinders
      performance of daily activities. OBJECTIVE: To assess the evidence on the
      effectiveness of task-specific training on sitting and standing function in
      individuals with SCI across the continuum of care. METHODS: A systematic search
      was conducted on literature published to June 2016 using people (acute or chronic
      SCI), task-specific interventions compared to conventional physical therapy, and
      outcome (sitting or standing balance function). The PEDro scale was used to
      investigate the susceptibility to bias and trial quality of the randomized
      controlled trials (RCTs). A standardized mean difference (SMD) was conducted to
      investigate the effect size for interventions with sitting or standing balance
      outcomes. RESULTS: Nineteen articles were identified; three RCTs, two prospective
      controlled trials, one cross-over study, nine pre-post studies and four
      prospective cohort studies. RCT and cross-over studies were rated from 6 to 8
      indicating good quality on the PEDro scale. The SMD of task-specific
      interventions in sitting compared to active and inactive (no training) control
      groups was -0.09 (95% CI: -0.663 to 0.488) and 0.39 (95% CI: -0.165 to 0.937)
      respectively, indicating that the addition of task-specific exercises did not
      affect sit and reach test performance significantly. Similarly, the addition of
      BWS training did not significantly affect BBS compared to conventional physical
      therapy -0.36 (95% CI: -0.840 to 0.113). Task-specific interventions reported in
      uncontrolled trials revealed positive effects on sitting and standing balance
      function. CONCLUSION: Few RCT studies provided balance outcomes, and those that
      were evaluated indicate negligible effect sizes. Given the importance of balance
      control underpinning all aspects of daily activities, there is a need for further
      research to evaluate specific features of training interventions to improve both
      sitting and standing balance function in SCI.

PMID- 28738742
TI  - Effects of ERK1/2 kinases inactivation on the nigrostriatal system of Krushinsky
      Molodkina rats genetically prone to audiogenic seizures.
AB  - : Recently, we demonstrated that inhibition of ERK1/2 activity by SL-327
      treatment blocks seizure behavior in Krushinsky-Molodkina (KM) rats, which was
      mediated by altering of GABA and glutamate release mechanism in the hippocampus.
      Basal ganglia representing various subcortical cell groups play a significant
      role in the regulation of motor activity, including epileptiform seizures.
      OBJECTIVES:  To verify if nigrostriatal system could be also affected by SL-327
      treatment we analyzed the expression of tyrosine hydroxylase, D1 and D2 dopamine
      receptors, NR2B subunit of NMDA receptor as well as vesicular glutamate
      transporter VGLUT2 and glutamic acid decarboxylases GAD65/67 in the striatum and
      substantia nigra of KM rats. METHODS: Animals were injected i.p. with SL-327 (50
      mg/kg) 60 min before audio stimulation. After audiogenic stimulation the brains
      of control and SL 327 treated rats were removed for further immunohistochemical
      and biochemical analysis. RESULTS:  Obtained results demonstrated a decrease
      activity in synapsin I, and accumulation of VGLUT2 in the striatum after blockade
      of audiogenic seizure (AGS) by SL 327 that could lead to inhibition of glutamate
      release. While in the striatum GAD65/67 level was diminished, in the substantia
      nigra GAD65/67 was increased showing enhanced inhibitory output to the compact
      part of the substantia nigra. Analysis of dopaminergic system showed a
      significant reduction of tyrosine hydroxylase activity and expression in the
      substantia nigra, and decreased D1 and D2 receptor expression in the striatum. In
      summary, we propose that changes in the nigrostriatal system could be mediated by
      inhibitory effect of SL 327 on AGS expression.

PMID- 28738743
TI  - Distraction of the temporomandibular joint condyle in patients with unilateral
      non-reducing disc displacement: Fact or fiction?
AB  - OBJECTIVES: This study investigated the distractive effect of a unilateral pivot
      splint on patients with unilateral disc displacement without reduction. METHODS:
      The study group was comprised of 18 patients who had no history of treatment with
      removable prosthetic restorations of molars, premolars, or canine teeth, and no
      previous treatment for temporomandibular disorder. Joint spaces measurements made
      on magnetic resonance images indicated the affected side to be narrower than the
      healthy side. Unilateral distraction splints were made for all patients. An
      ultrasonic motion analyzer was used to measure the vertical shift occurring on
      the affected side as patients closed their mouths with maximal force with the
      splint in their mouths. RESULTS: Closing with maximal force on the unilateral
      distraction splint led to a noticeable downward movement of the affected condyle.
      DISCUSSION: The findings of this study indicate that the TMJ condyle of patients
      with unilateral disc displacement without reduction may be unilaterally
      distracted if the articular space is narrowed.

PMID- 28738744
TI  - Pain profiles in a community dwelling population following spinal cord injury: a
      national survey.
AB  - CONTEXT: While as many as 60% of patients with spinal cord injury (SCI) develop
      chronic pain, limited data currently exists on the prevalence and profile of pain
      post-SCI in community dwelling populations. STUDY DESIGN: A cross-sectional
      population survey. SETTING: Primary care. PARTICIPANTS: Community dwelling adults
      with SCI. METHODS: Following ethical approval members registered to a national
      SCI database (n=1,574) were surveyed. The survey included demographic and SCI
      characteristics items, the International Spinal Cord Injury Pain Basic Data Set
      (version 1) the Douleur Neuropathique 4 questionnaire (interview) and questions
      relating to health care utilisation. Data were entered into the Statistical
      Package for the Social Sciences (version 20) Significance was set P < 0.05 for
      between group comparisons. RESULTS: In total 643 (41%) surveys were returned with
      458 (71%) respondents experiencing pain in the previous week. Neuropathic pain
      (NP) was indicated in 236 (37%) of responses and nociceptive pain in 206 (32%)
      Common treatments for pain included medications n=347 (76%) massage n=133 (29%)
      and heat n=115 (25%). Respondents with NP reported higher pain intensities and
      increased healthcare service utilisation (P= < 0.001) when compared to those with
      nociceptive pain presentations. A higher proportion of females than males
      reported pain (P = 0.003) and NP (P = 0.001) and those unemployed presented with
      greater NP profiles compared with those in education or employment (P = 0.006).
      CONCLUSION: Pain, in particular NP post SCI interferes with daily life, increases
      health service utilisation and remains refractory to current management
      strategies. Increased availability of multi-disciplinary pain management and
      further research into management strategies is warranted.

PMID- 28738745
TI  - Is ultrasound-guided suction curettage a reliable option for treatment of
      cesarean scar pregnancy? A cross-sectional retrospective study.
AB  - PURPOSE: The purpose of our study is to present clinical courses and outcomes of
      50 first-trimester cesarean scar pregnancy (CSP) cases, which are managed either
      with transabdominal ultrasound (TAUS)-guided suction curettage alone or abdominal
      hysterotomy. METHODS: We retrospectively analyzed our records from 2011 to 2016
      at a single-center. TAUS-guided suction curettage alone was preferred in
      hemodynamically stable patients when the myometrial thickness was >=3 mm and
      there was no vascular invasion. If the myometrial thickness was <3 mm and/or
      vascular invasion was present, then hysterotomy was preferred. RESULTS:
      Statistical analysis of age, gravidity, parity, history of previous CS (>=3 or
      <3), presence of embryonic cardiac activity, complaints (vaginal bleeding, pelvic
      pain, or both), preoperative and postoperative hemoglobin levels (g/dl), blood
      transfusion, initial serum beta-hCG levels, and duration to resolution of beta
      hCG demonstrated no significant difference between TAUS-guided suction curettage
      and abdominal hysterotomy groups. There was a significant difference between two
      groups in terms of postoperative length of stay in the hospital and gestational
      age. CONCLUSION: TAUS-guided suction curettage in selected cases may be
      considered as a reliable first-line treatment option due to its low cost, ease of
      application, lower side-effect profile, and potentially minimal influence on
      future fertility in CSP patients that are hemodynamically stable.

PMID- 28738746
TI  - How do clinical competency committees use different sources of data to assess
      residents' performance on the internal medicine milestones?A mixed methods pilot
      study.
AB  - PURPOSE: This study examines how Clinical Competency Committees (CCCs) synthesize
      assessment data to make judgments about residents' clinical performances.
      METHODS: Between 2014 and 2015, after four six-month reporting periods to the
      Accreditation Council for Graduate Medical Education (ACGME), 7 of 16 CCC faculty
      at Rush University Medical Center completed questionnaires focused on their
      perspectives about rating residents on their achievement of the milestones and
      participated in a focus group. Qualitative data were analyzed using grounded
      theory. Milestones ratings for two six-month ACGME reporting cycles (n = 100
      categorical residents) were also analyzed. RESULTS: CCC members weighted resident
      rotation ratings highest (weight = 37%), followed by faculty rotation comments
      (weight = 27%) and personal experience with residents (weight = 14%) for making
      judgments about learner's milestone levels. Three assessment issues were
      identified from qualitative analyses: (1) "design issues" (e.g. problems with
      available data or lack thereof); (2) "synthesis issues" (e.g. factors influencing
      ratings and decision-making processes) and (3) "impact issues" (e.g. how CCC
      generated milestones ratings are used). CONCLUSIONS: Identifying factors that
      affect assessment at all stages of the CCC process can contribute to improving
      assessment systems, including support for faculty development for CCCs.
      Recognizing challenges in synthesizing first and second-hand assessment data is
      an important step in understanding the CCC decision-making process.

PMID- 28738747
TI  - How directional microphones affect speech recognition, listening effort and
      localisation for listeners with moderate-to-severe hearing loss.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of directional
      microphone use on laboratory measures of sentence recognition, listening effort
      and localisation. An additional purpose of this study was to evaluate the effects
      of asymmetric directional microphone use on the same laboratory measures. DESIGN:
      Three hearing aid conditions were evaluated: (1) bilateral omnidirectional
      microphones, (2) bilateral directional microphones and (3) asymmetric microphones
      (directional microphone for only one hearing aid). Sentence recognition
      performance was evaluated using a connected speech test. Listening effort was
      evaluated using a dual-task paradigm with a response time-based secondary task
      requiring word categorisation. Localisation was examined using a complex task
      requiring localisation and recall of speech originating from one of four
      loudspeakers in the horizontal plane (-60 degrees , -45 degrees , +45 degrees ,
      +60 degrees ). STUDY SAMPLE: Eighteen adults (M = 61.8 years) with symmetrical,
      moderate-to-severe hearing loss participated. RESULTS: Performance on each task
      was analysed separately using a repeated measures analysis of variance. Results
      revealed directional benefits for sentence recognition and listening effort, but
      microphone setting did not affect localisation. Performance was equivalent with
      symmetric and asymmetric directional configurations. CONCLUSIONS: Bilateral and
      asymmetric directional microphone configurations equally improved sentence
      recognition and listening effort; neither affected localisation or recall.

PMID- 28738748
TI  - Liesegang Rings: Extremely Rare Structures in Malignant Lesions.

PMID- 28738749
TI  - An update on multiple sclerosis in children: diagnosis, therapies, and prospects
      for the future.
AB  - INTRODUCTION: Multiple sclerosis (MS), a chronic demyelinating disease of the
      central nervous system, is increasingly being recognized in children and
      adolescents. Pediatric MS follows a relapsing-remitting course at onset, with a
      risk for early cognitive impairment. Areas covered: In this review, we discuss
      the clinical features of acute demyelinating syndromes in children and risk
      factors that increase the likelihood of a diagnosis of MS. We also address the
      application of diagnostic criteria for MS in children, immunological features,
      therapeutic options and psychosocial considerations for children and adolescents
      with MS. Expert commentary: Collaborative multicenter clinical trials and
      research efforts are key to the advancement in understanding the pathophysiology
      and therapeutic strategies for multiple sclerosis across the lifespan.

PMID- 28738750
TI  - Pregnancy outcome in patients with Takayasu's arteritis: cohort study and review
      of the literature.
AB  - OBJECTIVE: The objective of this study is to investigate the clinical features of
      pregnancy in women with Takayasu's arteritis managed in a tertiary medical center
      and review the literature in order to establish the course and recommended follow
      up and treatment for these pregnancies. MATERIALS AND METHODS: Retrospective
      analysis of 20 pregnancies in 6 women with Takayasu's arteritis. Patients were
      recruited from the high risk pregnancy clinics at Sheba Medical Center, where
      follow up included strict control of blood pressure and treatment of obstetric
      and disease-related complications. RESULTS: Mean maternal age was 29.3 +/- 3
      years. Thirty-six patients had both supra and infradiaphragmatic arterial
      disease, of them two had an abdominal aorta involvement and three out of six
      patients had an isolated supradiaphragmatic disease. Of 20 pregnancies, six
      pregnancies (30%) resulted in early spontaneous miscarriages, and one pregnancy
      was terminated at 17 weeks due to fetal anomalies. The remaining 13 pregnancies
      (65%) resulted in live births. Three out of 13 (23%) neonates were small-for
      gestational-age. The most common complication was maternal hypertension affecting
      8/13 (61.5%) pregnancies. Preeclampsia occurred in one pregnancy. Four out of 13
      (30.7%) pregnancies necessitated preterm induction of labor due to obstetric
      indications or uncontrolled disease. CONCLUSIONS: Although Takayasu's arteritis
      is associated with pregnancy complications, tight preconception disease control,
      strict follow up, and targeted treatment of high blood pressure can result in
      positive pregnancy outcome.

PMID- 28738752
TI  - Physical functioning and activities of daily living in adults with amyoplasia,
      the most common form of arthrogryposis. A cross-sectional study.
AB  - BACKGROUND: Amyoplasia, the most common form of arthrogryposis is characterized
      by typical deformities of the joints and replacement of skeletal muscles by
      fibrous tissue and fat. There is sparse literature on adaptation to adult life
      with amyoplasia. PURPOSE: To describe physical function and activity strategies
      in adults with amyoplasia, as this knowledge is important for relevant function
      enhancing measures. MATERIALS AND METHODS: Twenty-two adults (20-91 years) with
      amyoplasia participated. Demographic factors and clinical history were
      registered. Body proportions were measured. Joint mobility and muscle strength in
      the upper limbs were examined. The Functional Independent Measure was used to
      assess performance of activities of daily living. Compensatory strategies were
      described. RESULTS: The majority had undergone comprehensive conservative and
      surgical treatment. Mean height was below typical. Range of motion was below
      lower limit of normal in most joints, passive range of motion was mainly larger
      than active. Muscle strength was reduced for most movements. Seven were
      independent in all activities. Need of assistance was highest regarding bathing
      and dressing. A variety of compensatory strategies were used. CONCLUSIONS: Adults
      with amyoplasia are heterogeneous regarding function. Independence in everyday
      life requires a combination of muscle strength to move against gravity, ability
      to passive joint motion, and use of compensatory strategies. Implications for
      rehabilitation The ability to joint motion in the upper extremities is essential
      for independency in activities of daily living, especially when the muscle
      strength is impaired. Training of muscle strength is recommended, whenever
      possible, as muscle strength to move against gravity makes the performing of
      everyday tasks easier. The use of compensatory techniques, adaptions to the
      environment and relevant, often custom made, assistive devices is required to
      perform activities of daily living. Living an active life with physical
      challenges like in amyoplasia requires flexible and individually adapted
      solutions.

PMID- 28738751
TI  - A single-center retrospective study: Clinical features of different types of Budd
      Chiari syndrome in Chinese patients in the Hubei area.
AB  - Background The characteristics and prevalence of Budd-Chiari syndrome in China
      remain unclear. This study aimed to analyze the clinical features of Budd-Chiari
      syndrome in Chinese patients in the Hubei area. Methods One-hundred and thirty
      patients with Budd-Chiari syndrome, admitted to Union Hospital from January 2002
      to January 2011, were included in this retrospective study. Clinical features,
      laboratory data, imaging characteristics, and cumulative patency rates were
      analyzed. Results Of the 130 patients with Budd-Chiari syndrome, 77 were men
      (59.2%) and 53 women (40.8%). Budd-Chiari syndrome was more commonly associated
      with inferior vena cava block (56.9%, 74/130) than hepatic vein block (19.2%,
      25/130) and combined inferior vena cava/hepatic vein block (23.9%, 31/130). The
      clinical features of Budd-Chiari syndrome varied based on the location of the
      obstruction. The incidence of bilirubin abnormality, elevated alkaline
      phosphatase, and gamma-glutamyl peptide transferase levels was common in patients
      with Budd-Chiari syndrome. Liver injury was more severe in cases with combined
      inferior vena cava/hepatic vein block than in the other two types of Budd-Chiari
      syndrome. Color Doppler ultrasound imaging was better for the diagnosis of
      hepatic vein obstruction, while computed tomography and magnetic resonance
      imaging were superior in diagnosing inferior vena cava obstruction. The
      cumulative 1-, 5-, and 10-year patency rates were 97%, 69%, and 59%,
      respectively. Univariate analysis indicated that liver cirrhosis was an
      independent risk factor of recurrence. Conclusion The most prevalent type of Budd
      Chiari syndrome is inferior vena cava obstruction in Chinese patients in the
      Hubei area. Different types of Budd-Chiari syndrome have diverse clinical and
      biochemical features, which may assist clinicians in diagnosing Budd-Chiari
      syndrome. Liver cirrhosis was found as an independent risk factor of recurrence.

PMID- 28738753
TI  - Genetic predictors of celiac disease, lactose intolerance, and vitamin D function
      and presence of peptide morphins in urine of children with neurodevelopmental
      disorders.
AB  - Gastrointestinal disturbances, nutritional deficiencies, and food intolerances
      are frequently observed in children with neurodevelopmental disorders (NDD). To
      reveal possible association of celiac disease risk variants (HLA-DQ), lactose
      intolerance associated variant (LCT-13910C>T) as well as variant associated with
      vitamin D function (VDR FokI) with NDD, polymerase chain reaction-based
      methodology was used. Additionally, intestinal peptide permeability was estimated
      in NDD patients and healthy children by measuring the level of peptides in urine
      using high-performance liquid chromatography. Levels of opioid peptides,
      casomorphin 8, and gluten exorphin C were significantly elevated in urine samples
      of NDD patients (P = 0.004 and P = 0.005, respectively), but no association of
      genetic risk variants for celiac disease and lactose intolerance with NDD was
      found. Our results indicate that increased intestinal peptide permeability
      observed in analyzed NDD patients is not associated with genetic predictors of
      celiac disease or lactose intolerance. We have also found that FF genotype of VDR
      FokI and lower serum levels of vitamin D (25-OH) showed association with
      childhood autism (CHA), a subgroup of NDD. We hypothesize that vitamin D might be
      important for the development of CHA.

PMID- 28738754
TI  - Pralatrexate: a comprehensive update on pharmacology, clinical activity and
      strategies to optimize use.
AB  - It has been nearly 8 years since pralatrexate became the first drug approved by
      the U.S. Food and Drug Administration for the treatment of relapsed or refractory
      peripheral T-cell lymphoma (PTCL). Like most drugs approved for a particular
      clinical indication, as much or more is learned once it enters mainstream use as
      in the years leading up to regulatory approval. Over the past several years, many
      diverse lines of research have shed new insight into both the agent, and the
      diseases it treats. In this review, we will bring the reader up to date on the
      many new aspects related to pralatrexate's pharmacology, activity across the
      panoply of T-cell lymphoproliferative malignancies, as well as some new and
      emerging guidelines that are likely to improve its safety profile. Finally, the
      review will close with the many new lines of evidence building a rationale for
      the combination of these novels: novel combination, and the vision for new
      platforms in PTCL care.

PMID- 28738755
TI  - QSAR, DFT and molecular modeling studies of peptides from HIV-1 to describe their
      recognition properties by MHC-I.
AB  - Human immunodeficiency virus type-1 (HIV-1) has infected more than 40 million
      people around the world. HIV-1 treatment still has several side effects, and the
      development of a vaccine, which is another potential option for decreasing human
      infections, has faced challenges. This work presents a computational study that
      includes a quantitative structure activity relationship(QSAR) using density
      functional theory(DFT) for reported peptides to identify the principal quantum
      mechanics descriptors related to peptide activity. In addition, the molecular
      recognition properties of these peptides are explored on major histocompatibility
      complex I (MHC-I) through docking and molecular dynamics (MD) simulations
      accompanied by the Molecular Mechanics Generalized Born Surface Area (MMGBSA)
      approach for correlating peptide activity reported elsewhere vs. theoretical
      peptide affinity. The results show that the carboxylic acid and hydroxyl groups
      are chemical moieties that have an inverse relationship with biological activity.
      The number of sulfides, pyrroles and imidazoles from the peptide structure are
      directly related to biological activity. In addition, the HOMO orbital energy
      values of the total absolute charge and the Ghose-Crippen molar refractivity of
      peptides are descriptors directly related to the activity and affinity on MHC-I.
      Docking and MD simulation studies accompanied by an MMGBSA analysis show that the
      binding free energy without considering the entropic contribution is
      energetically favorable for all the complexes. Furthermore, good peptide
      interaction with the most affinity is evaluated experimentally for three
      proteins. Overall, this study shows that the combination of quantum mechanics
      descriptors and molecular modeling studies could help describe the immunogenic
      properties of peptides from HIV-1.

PMID- 28738756
TI  - Nostalgia's place among self-relevant emotions.
AB  - How is nostalgia positioned among self-relevant emotions? We tested, in six
      studies, which self-relevant emotions are perceived as most similar versus least
      similar to nostalgia, and what underlies these similarities/differences. We used
      multidimensional scaling to chart the perceived similarities/differences among
      self-relevant emotions, resulting in two-dimensional models. The results were
      revealing. Nostalgia is positioned among self-relevant emotions characterised by
      positive valence, an approach orientation, and low arousal. Nostalgia most
      resembles pride and self-compassion, and least resembles embarrassment and shame.
      Our research pioneered the integration of nostalgia among self-relevant emotions.

PMID- 28738757
TI  - Determinants of sleep quality among pregnant women in China: a cross-sectional
      survey.
AB  - PURPOSE: Sleep disturbances are common during pregnancy, yet few studies are
      currently available regarding the determinants of sleep quality among pregnant
      women in China. This study aimed to: (a) calculate the prevalence of sleep
      disorder during pregnancy, (b) examine the difference in sleep quality among
      three trimesters, and (c) identify determinants of sleep quality in pregnant
      women. MATERIALS AND METHODS: This study was designed as a cross-sectional
      survey. Five hundred pregnant women were recruited at the outpatient department
      of obstetrics and gynecology of two teaching hospitals in central China. Five
      selfreport questionnaires were used for gathering data, including information of
      sample characteristics, sleep quality (Pittsburgh Sleep Quality Index (PSQI)),
      prenatal depression (the Edinburgh Postnatal Depression Scale (EPDS)), perceived
      stress (Perceived Stress Scale (PSS)), and perceived social support
      (Multidimensional Scale of Perceived Social Support (MSPSS)). RESULTS: A total of
      454 pregnant women participated in the study between September 2016 and April
      2017. Eighty-seven percent pregnant women experienced sleep disorder (PSQI score
      >5). Poorer global sleep quality, subjective sleep quality, lower sleep
      efficiency and sleep disturbances were most prevalent during third trimester. The
      significant contributors to sleep quality for pregnant women were prenatal
      depression, maternal age, and gestational age. CONCLUSIONS: Sleep disorder is
      very common in pregnant women from China. Depressive symptoms, increased maternal
      age, and gestational age are determinants of sleep quality. These determinants
      can assist healthcare professionals in preventative intervention.

PMID- 28738758
TI  - Laparoscopic treated neuralgia after inguinal hernia repair: case report and
      literature review.
AB  - BACKGROUND: Neuralgia after inguinal hernia repair is a known but potential
      invalidating complication with a reported incidence of 10-12%. Diagnosis and
      treatment can be challenging. Based on a case report and literature review,
      disease aspects and treatment options including laparoscopic (triple) neurectomy
      are discussed. METHODS: A case of laparoscopic treated neuralgia after hernia
      inguinalis repair is reported. After an extensive MeSH-term based literature
      search, 26 articles were included for in-depth analysis and literature review.
      RESULTS: Pharmacotherapy encounters high numbers needed to treat and technical
      procedures often require re-intervention. Surgery should only be considered after
      one year of unsuccessful conventional treatment. Laparoscopic (triple) neurectomy
      is a minimal invasive procedure, providing optimal visualisation of the inguinal
      nerves. It is reported to be a safe and effective treatment option for refractory
      inguinal neuralgia. CONCLUSIONS: Chronic neuralgia can be a severe complication
      after inguinal hernia repair. When pharmacotherapy and technical interventions
      are not sufficient, a laparoscopic (triple) neurectomy can be a promising, safe
      and effective treatment option.

PMID- 28738759
TI  - Views of individuals with spinal cord injury on the use of wearable cameras to
      monitor upper limb function in the home and community.
AB  - OBJECTIVE: Hand function impairment after cervical spinal cord injury (SCI) can
      significantly reduce independence. Unlike current hand function assessments,
      wearable camera systems could potentially measure functional hand usage at home,
      and thus benefit the development of neurorehabilitation strategies. The objective
      of this study was to understand the views of individuals with SCI on the use of
      wearable cameras to track neurorehabilitation progress and outcomes in the
      community. DESIGN: Questionnaires. SETTING: Home simulation laboratory.
      PARTICIPANTS: Fifteen individuals with cervical SCI. OUTCOME MEASURES: After
      using wearable cameras in the simulated home environment, participants completed
      custom questionnaires, comprising open-ended and structured questions. RESULTS:
      Participants showed relatively low concerns related to data confidentiality when
      first-person videos are used by clinicians (1.93 +/- 1.28 on a 5-point Likert
      scale) or researchers (2.00 +/- 1.31). Storing only automatically extracted
      metrics reduced privacy concerns. Though participants reported moderate privacy
      concerns (2.53 +/- 1.51) about wearing a camera in daily life due to certain
      sensitive situations (e.g. washrooms), they felt that information about their
      hand usage at home is useful for researchers (4.73 +/- 0.59), clinicians (4.47 +/
      0.83), and themselves (4.40 +/- 0.83). Participants found the system moderately
      comfortable (3.27 +/- 1.44), but expressed low desire to use it frequently (2.87
      +/- 1.36). CONCLUSION: Despite some privacy and comfort concerns, participants
      believed that the information obtained would be useful. With appropriate
      strategies to minimize the data stored and recording duration, wearable cameras
      can be a well-accepted tool to track function in the home and community after
      SCI.

PMID- 28738760
TI  - Substitution urethroplasty for anterior urethral stricture repair: comparison
      between lingual mucosa graft and pedicled skin flap.
AB  - OBJECTIVES: The aim of this study was to compare the effectiveness and outcomes
      of lingual mucosa graft (LMG) urethroplasty versus pedicled skin flap (PSF)
      urethroplasty in the repair of anterior urethral strictures. MATERIALS AND
      METHODS: A retrospective study in one urological center examined 293 male
      patients with anterior urethral strictures who received substitution
      urethroplasty from 2006 to 2015. Of these, 199 patients received PSF
      urethroplasty and 94 received LMG urethroplasty. The causes of stricture included
      catheter damage, transurethral instrumentation, trauma, infection, tumor and
      radiotherapy. Strictures caused by lichen sclerosus, hypospadias repair or failed
      urethroplasty were excluded. The success rate of PSF versus LMG in different
      urethra positions was analyzed. RESULTS: Overall, PSF and LMG had similar success
      rates (83.4% vs 85.1%, p = 0.713). In distal penile urethra, penile skin flaps
      and LMG achieved similar success rates (87.7% vs 82.1%, p = 0.297), but in
      proximal penile urethra, scrotal flaps had relatively low success rates (69.0% vs
      LMG 83.3%, p = 0.345) and in bulbar urethra, perineal skin flaps had
      significantly lower success rates than LMG (66.7% vs 92.3%, p = 0.036).
      CONCLUSION: Lingual mucosa is a good material for the repair of urethral defects
      and achieves results similar to or even better than those of PSF. Scrotal skin
      and perineal skin had lower success rates.

PMID- 28738761
TI  - Peer-led Aboriginal parent support: Program development for vulnerable
      populations with participatory action research.
AB  - BACKGROUND: Participatory action research (PAR) is a credible, culturally
      appropriate methodology that can be used to effect collaborative change within
      vulnerable populations. AIM/OBJECTIVE: This PAR study was undertaken in a Western
      Australian metropolitan setting to develop and evaluate the suitability,
      feasibility and effectiveness of an Aboriginal peer-led home visiting programme.
      A secondary aim, addressed in this paper, was to explore and describe research
      methodology used for the study and provide recommendations for its implementation
      in other similar situations. METHODS: PAR using action learning sets was employed
      to develop the parent support programme and data addressing the secondary,
      methodological aim were collected through focus groups using semi-structured and
      unstructured interview schedules. Findings were addressed throughout the action
      research process to enhance the research process. RESULTS: The themes that
      emerged from the data and addressed the methodological aim were the need for safe
      communication processes; supportive engagement processes and supportive
      organisational processes. CONCLUSIONS: Aboriginal peer support workers (PSWs) and
      community support agencies identified three important elements central to their
      capacity to engage and work within the PAR methodology. This research has
      provided innovative data, highlighting processes and recommendations for child
      health nurses to engage with the PSWs, parents and community agencies to explore
      culturally acceptable elements for an empowering methodology for peer-led home
      visiting support. There is potential for this nursing research to credibly inform
      policy development for Aboriginal child and family health service delivery, in
      addition to other vulnerable population groups. Child health nurses/researchers
      can use these new understandings to work in partnership with Aboriginal
      communities and families to develop empowering and culturally acceptable
      strategies for developing Aboriginal parent support for the early years. Impact
      Statement Child health nurses and Aboriginal communities can collaborate through
      participatory action research to develop peer-led support for the early years.
      Indigenous Australian peoples are people who identify as Aboriginal or Torres
      Strait Islander. Respectfully, throughout this paper, they will be described as
      Aboriginal.

PMID- 28738762
TI  - Effects of neuroserpin on clinical outcomes and inflammatory markers in Chinese
      patients with acute ischemic stroke.
AB  - OBJECTIVE: Neuroserpin (NSP) is known for its neuroprotective effects. The aim of
      this study was to investigate the relationship between NSP level and clinical
      outcomes and inflammatory markers in Chinese patients with acute ischemic stroke.
      METHODS: A total of 133 patients with acute cerebral infarction (ischemia group)
      and 44 controls were recruited. The modified Rankin Scale (mRS) was used to
      determine the functional outcome three months after onset. We investigated the
      relationship between serum NSP levels [on admission and a decrease in NSP levels
      (10 days after admission versus on admission)] and serum levels of several
      inflammatory markers. RESULTS: We confirmed that NSP levels on admission in the
      ischemia group were significantly higher than those in the control group. NSP
      levels in patients with good outcomes were significantly higher than those in
      patients with poor outcomes. NSP levels on admission were associated with having
      a good outcome in these patients. We found that a larger decrease in NSP levels
      (on admission vs. 10 days after admission) was correlated with lower serum levels
      of IL-6, IL-1beta, and ICAM-1 10 days after admission. CONCLUSIONS: A larger
      decrease in NSP levels related to lower levels of inflammatory marker, while
      higher NSP levels were associated with lower inflammatory markers and better
      functional outcomes. Decreasing the infarct size may play a role in this process.
      These results provide more evidence of the neuroprotective effect of NSP in
      cerebral ischemic patients. Decrease in the Serum NSP level and NSP level at
      admission may be considered as potential predictive factors for outcome of acute
      ischemic stroke.

PMID- 28738763
TI  - An Evaluation of the Clinical Therapeutic Effect of Lixisenatide in Type 2
      Diabetes Patients: A Systematic Literature Review.
AB  - BACKGROUND: With cardiovascular disease accounting for approximately 50% of
      deaths in patients diagnosed with type 2 diabetes, it is pertinent to initiate
      anti-diabetic medications with cardiovascular benefits. This systematic clinical
      review critically examines the clinical therapeutic effect of lixisenatide.
      METHODS: Data were gathered from articles indexed in PubMed, Google Scholar and
      Medline from 2010 - 2017, with the following search terms, "lixisenatide" and
      "GLP-1 receptor agonist". Studies written in the English language were included.
      RESULTS: Thirteen clinical studies which evaluated the efficacy of lixisenatide
      were analyzed. Results from these studies showed that lixisenatide is an
      effective monotherapy in the reduction of glycated hemoglobin (A1C), Postprandial
      Glucose (PPG) and Fasting Blood Glucose (FPG). As an add-on therapy to metformin
      or sulfonylureas and insulin, it was found to be clinically effective compared to
      placebo. In all reviewed trials, there were higher proportions of patients who
      achieved A1C < 7% or < 6.5% compared to placebo without a corresponding increase
      in weight. Finally, the use of lixisenatide was not associated with an increased
      risk of cardiovascular events. The most common adverse events in all lixisenatide
      groups were nausea, vomiting, and diarrhea. CONCLUSION: Lixisenatide appears to
      be safe and effective therapy for the management of type 2 diabetes mellitus. It
      is not associated with either the risk of cardiovascular events or symptomatic
      hypoglycemia. Finally, lixisenatide may be best used as an adjunct therapy for
      patients who are inadequately controlled with other diabetic medications, or
      select group of patients at risk of insulin induced obesity, hypertension or
      heart failure.

PMID- 28738765
TI  - Effect of Heart Rate on Arterial Stiffness as Assessed by Pulse Wave Velocity.
AB  - Vascular assessment is becoming increasingly important in the diagnosis of
      cardiovascular diseases. In particular, clinical assessment of arterial
      stiffness, as measured by pulse wave velocity (PWV), is gaining increased
      interest due to the recognition of PWV as an influential factor on the prognosis
      of hypertension as well as being an independent predictor of cardiovascular and
      all-cause mortality. Whilst age and blood pressure are established as the two
      major determinants of PWV, the influence of heart rate on PWV measurements
      remains controversial with conflicting results being observed in both acute and
      epidemiological studies. In a majority of studies investigating the acute effects
      of heart rate on PWV, results were confounded by concomitant changes in blood
      pressure. Observations from epidemiological studies have also failed to converge,
      with approximately just half of such studies reporting a significant blood
      pressure-independent association between heart rate and PWV. Further to the lack
      of consensus on the effects of heart rate on PWV, the possible mechanisms
      contributing to observed PWV changes with heart rate have yet to be fully
      elucidated, although many investigators have attributed heart-rate related
      changes in arterial stiffness to the viscoelasticity of the arterial wall. With
      elevated heart rate being an independent prognostic factor of cardiovascular
      disease and its association with hypertension, the interaction between heart rate
      and PWV continues to be relevant in assessing cardiovascular risk.

PMID- 28738766
TI  - Molecular Dynamics and Biological Evaluation of 2-chloro-7-cyclopentyl- 7H
      pyrrolo[2,3-d]pyrimidine Derivatives Against Breast Cancer.
AB  - AIM AND OBJECTIVE: Inspired by the impressive biological properties of
      pyrrolo[2,3- d]pyrimidine units, the objective of this study was to synthesize
      some new derivatives of heterocyclic compounds with different substituent's using
      solvent-free microwave irradiation conditions from readily available starting
      material. The synthesized compounds were screened for their in vitro anti
      microbial, anti-oxidant, anti-cancer activities and theoretical molecular docking
      studies. MATERIAL AND METHODS: Structural elucidation of the synthesized
      compounds was determined on the basis of various spectroscopic methods.
      Synthesized compounds have been evaluated for their in vitro antimicrobial
      activity (MIC) against various microbial strains. After the primary screening,
      synthesised compounds are further studied for anti-oxidant activity using DPPH
      assay method, anticancer activity against MCF-7 cell line using MTT assay and
      molecular docking studies. Moreover, molecular dynamics and simulation was done
      for best compound using GROMACS. RESULTS: A series of 2-chloro-7-cyclopentyl-7H
      pyrrolo[2,3-d]pyrimidine derivatives 6(a-f), 7(a-c) and 8(a-c) were synthesised
      using solvent-free microwave irradiation technique. Among all the synthesized
      compounds, compounds 6e (51.35 MUg/mL) and 6f (60.14 ug/mL) showed better
      activity profile against MCF-7 cell line for breast cancer activity. Compounds 6f
      and 6d have shown potent antibacterial activity against most of the employed
      strains, especially against S. pneumoniae, B. cerus and S. aureus. Compound 7a
      (52.21 ug/mL) showed high potential activity for antioxidant using DPPH assay.
      Molecular docking study showed good binding of these compounds to the active site
      of ER- alpha with binding energy ranging from -7.12 kcal/mol to -1.21 kcal/mol.
      Furthermore, molecular dynamics and simulation was conducted for best pose
      interacted compound 6e with active site of protein to study its stability and
      behaviour in nanoscale. CONCLUSION: The present research work is intended for
      facile and efficient green synthesis of various biologically useful potent bio
      active molecules from inexpensive and readily available starting substrates under
      mild reaction condition. These classes of synthesized various heterocyclic
      compounds holds a great importance to discover newer anti-microbial, anti-oxidant
      and anti-cancer drugs in future prospects. Further structural modification in
      these structures will be of interest and may result in compounds having a better
      therapeutic and biological activity. Hence, this efficient green synthetic
      protocol and biological results of newly synthesized heterocyclic derivatives are
      found to be interesting lead molecules for bioactivity in the near future. It
      could be considered for investigation of their mode of action and for further
      development.

PMID- 28738764
TI  - Neuroprotection by (endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative
      Diseases.
AB  - BACKGROUND: Emerging neuroprotective strategies are being explored to preserve
      the retina from degeneration, that occurs in eye pathologies like glaucoma,
      diabetic retinopathy, age-related macular degeneration, and retinitis pigmentosa.
      Incidentally, neuroprotection of retina is a defending mechanism designed to
      prevent or delay neuronal cell death, and to maintain neural function following
      an initial insult, thus avoiding loss of vision. METHODS: Numerous studies have
      investigated potential neuroprotective properties of plant-derived
      phytocannabinoids, as well as of their endogenous counterparts collectively
      termed endocannabinoids (eCBs), in several degenerative diseases of the retina.
      eCBs are a group of neuromodulators that, mainly by activating G protein-coupled
      type-1 and type-2 cannabinoid (CB1 and CB2) receptors, trigger multiple signal
      transduction cascades that modulate central and peripheral cell functions. A fine
      balance between biosynthetic and degrading enzymes that control the right
      concentration of eCBs has been shown to provide neuroprotection in traumatic,
      ischemic, inflammatory and neurotoxic damage of the brain. RESULTS: Since the
      existence of eCBs and their binding receptors was documented in the retina of
      numerous species (from fishes to primates), their involvement in the visual
      processing has been demonstrated, more recently with a focus on retinal
      neurodegeneration and neuroprotection. CONCLUSION: The aim of this review is to
      present a modern view of the endocannabinoid system, in order to discuss in a
      better perspective available data from preclinical studies on the use of eCBs as
      new neuroprotective agents, potentially useful to prevent glaucoma and retinal
      neurodegenerative diseases.

PMID- 28738767
TI  - Synthesis and Anticancer Evaluation of Thiazacridine Derivatives Reveals New
      Selective Molecules to Hematopoietic Neoplastic Cells.
AB  - AIM AND OBJECTIVE: Cancer has become one of the leading causes of morbidity and
      mortality worldwide. Limitations associated with existing agents increase the
      need to develop more effective anticancer drugs to improve the therapeutic
      arsenal available. The aim of this study was to synthesize and evaluate the
      antiproliferative effects of three new thiazacridine derivatives. MATERIAL AND
      METHODS: Using a three steps synthesis reaction, three novel thiazacridine
      derivatives were obtained and characterized: (Z)-5-acridin-9-ylmethylene-3-(4
      methyl-benzyl)-4-thioxo-thiazolidin- 2-one (LPSF/AC-99), (Z)-5-acridin-9
      ylmethylene-3-(4-chloro-benzyl)-4-thioxo-thiazolidin-2- one (LPSF/AC-119) and (Z)
      5-acridin-9-ylmethylene-3-(3-chloro-benzyl)-4-thioxo-thiazolidin-2- one (LPSF/AC
      129). Toxicity and selectivity assays were performed by colorimetric assay. Then,
      changes in cell cycle and cell death induction mechanisms were assessed by flow
      cytometry. RESULTS: All compounds exhibited cytotoxicity to Raji (Burkitt's
      lymphoma) and Jurkat (acute T cell leukemia) cells, where LPSF/AC-119 showed best
      IC50 values (0.6 and 1.53 u M, respectively). LPSF/AC-129 was the only cytotoxic
      compound in glioblastoma cell line NG97 (IC50 = 55.77 u M). None of the compounds
      were toxic to normal human cells and induced neoplastic cell death primarily by
      apoptosis. CONCLUSION: All derivatives were more cytotoxic to hematopoietic
      neoplastic cells when compared to solid tumor derived cells. All three compounds
      are promising for in vivo and combination therapy studies against cancer.

PMID- 28738768
TI  - Current Status of the Pharmacokinetics and Pharmacodynamics of HIV-1 Entry
      Inhibitors and HIV Therapy.
AB  - BACKGROUND: Human Immunodeficiency Virus (HIV) entry inhibitors target the first
      step of the HIV life cycle and efficiently inhibit HIV from infecting the immune
      cells which is a key prerequisite for viral spread. Because of their unique
      mechanism of action on cell-cell transmission, they may provide a promising
      perspective for the treatment of AIDS. METHOD: Maraviroc (MVC) and Enfuvirtide
      (ENF) have been approved by the FDA for the treatment of HIV-1 infection.
      Attachment inhibitors (BMS-663068 and TNX-355) and co-receptor inhibitors (PRO
      140 and cenicriviroc (CVC)) have reached phase II or III clinical trials. These
      entry inhibitors show beneficial pharmacokinetics and substantial reductions of
      plasma HIV-1 RNA load in HIV infected patients. RESULTS: Most entry inhibitors
      are generally safe, without serious Adverse Event (AE) or AE leading to
      discontinuation. The pharmacokinetics of MVC, CVC and BMS-663068 was affected by
      CYP3A4 inhibitors or inducers. The FDA has proposed that the dosage of MVC (300
      mg, BID, orally) be adjusted to half or two-fold for patients if it is combined
      with a major CYP3A4 inhibitor or inducer, respectively. Researchers suggested
      that the dosage of CVC (50-75 mg, QD, orally) may also need adjustment but the
      dosage of BMS-663068 (600 mg, BID, orally) does not. CONCLUSION: The standard,
      recommended ENF dosage is 90 mg BID, injected subcutaneously for adults, and 2
      mg/kg BID, up to a maximum dose of 90 mg, injected subcutaneously for pediatric
      patients. TNX-355 (10-15 mg/kg, BID, intravenously) and PRO-140(5-10 mg/kg, BID,
      intravenously; 324 mg, biweekly, subcutaneously) are administered by intravenous
      infusion or subcutaneous injection.

PMID- 28738769
TI  - Endogenous Biomarkers to Assess Drug-Drug Interactions by Drug Transporters and
      Enzymes.
AB  - BACKGROUND: Drug-Drug Interactions (DDI) by modulation of drug transporters or
      drug metabolizing enzymes are common in multi-drug therapy. DDI potential of any
      new drug is assessed by conducting separate clinical studies using relevant probe
      substrates, which involves additional resource and cost. Recently, several
      endogenous compounds have been evaluated as substrates of transporters and
      enzymes that could be assessed as part of early clinical trials along with the
      assessment of drug pharmacokinetics, pharmacodynamics and safety studies. This
      enables an early readout on potential DDIs avoiding or minimally delaying the
      conduct of definitive DDI studies until later in clinical development. METHOD:
      This review describes various endogenous biomarkers reported for drug
      transporters and metabolizing enzymes with their advantages and limitations.
      CONCLUSION: Furthermore, the authors describe strategies to adopt while exploring
      a new endogenous biomarker, and factors to be considered in selection of
      biomarkers with the current challenges and opportunities.

PMID- 28738770
TI  - Effects of Resveratrol and Other Polyphenols on the Most Common Brain Age-Related
      Diseases.
AB  - BACKGROUND: With global increase in elderly population, modern societies must
      find strategies to reduce the consequences of aging process; thereby decreasing
      the incidence of age-related neurodegenerative diseases. Oxidative stress and
      recently inflammation, have been pointed out as the leading causes of brain
      aging. Thereby, the consumption or administration of antioxidant and anti
      inflammatory molecules, such as polyphenols, is a beneficial strategy recommended
      for preventing brain aging and several brain age-related diseases. METHODS AND
      RESULTS: Several studies suggest that long term consumption of dietary
      polyphenols offers protection against development of neurodegenerative diseases.
      These beneficial effects are in part due to their antioxidant and anti
      inflammatory properties, together with their positive role in the modulation of
      processes involved in the physiopathology of several neurodegenerative diseases
      (e.g., epigenetic factors, amyloid deposition, cholinesterase inhibition,
      autophagy, and neurotrophic factors, among others). Altogether, these molecules
      open the door to the research of new neuroprotective strategies. This review
      summarizes the latest discoveries in how polyphenols can exert positive effects
      on brain health in aging, emphasizing those effects on the diseases that most
      commonly affect the brain during aging: Parkinson's Disease (PD), Alzheimer's
      disease (AD), dementia and depression. Moreover, within are addressed the
      epigenetic effects of polyphenols as possible mediators in their positive effects
      on brain health, and the future challenges of research in this topic Conclusion:
      In brief, this review presents a report of state-of the art knowledge regarding
      the positive influences of polyphenols on the most common brain age-related
      diseases as well as in healthy brain aging.

PMID- 28738771
TI  - Fumitremorgins and Relatives - From Tremorgenic Compounds to Valuable Anti-Cancer
      Drugs.
AB  - BACKGROUND: Fumitremorgins are mycotoxins but can also inhibit cancer cells and
      reverse their drug resistance. OBJECTIVE: The bioactivity of prenylated cyclo-Trp
      Pro dipeptides and their derivatives concerning their application in anti-cancer
      therapies will be discussed. METHODS: Reports on the discovery and assessment of
      this class of fungal compounds are compiled from literature using Google Scholar
      and PubMed. The bioactivities of the natural compounds are discussed with the aim
      of their improvement for cancer therapy. RESULTS: Although a number of compounds
      of this class have been found, only a minority of them showed bioactivity in the
      applied bioassays. Fumitremorgins and related compounds are active against
      various cancer cells but they are also mycotoxins. Some of these natural
      compounds can arrest cancer cells in their cell cycle and some can block ABC
      transporters and reverse resistance in chemotherapy. Structure activity
      relationships have been deduced leading to the prediction of highly active
      compounds. Several easily accessible derivatives of these natural products have
      been discovered being highly selective and non-toxic. CONCLUSION: Sophisticated
      screening methods, high throughput screening, metabolic engineering, and
      synthetic biology are novel and promising technologies for the search for highly
      active drugs. Rapid gene sequencing in combination with engineered biosynthetic
      pathways should contribute substantially to novel pharmaceutics.

PMID- 28738772
TI  - Molecular Docking and Drug Discovery in beta-Adrenergic Receptors.
AB  - BACKGROUND: Evolution in computer engineering, availability of increasing amounts
      of data and the development of new and fast docking algorithms and software have
      led to improved molecular simulations with crucial applications in virtual high
      throughput screening and drug discovery. Moreover, analysis of protein-ligand
      recognition through molecular docking has become a valuable tool in drug design.
      OBJECTIVE: In this review, we focus on the applicability of molecular docking on
      a particular class of G protein-coupled receptors: the beta-adrenergic receptors,
      which are relevant targets in clinic for the treatment of asthma and
      cardiovascular diseases. RESULTS: We describe the binding site in beta-adrenergic
      receptors to understand key factors in ligand recognition along with the proteins
      activation process. Moreover, we focus on the discovery of new lead compounds
      that bind the receptors, on the evaluation of virtual screening using the active/
      inactive binding site states, and on the structural optimization of known
      families of binders to improve beta-adrenergic affinity. We also discussed
      strengths and challenges related to the applicability of molecular docking in
      beta-adrenergic receptors. CONCLUSION: Molecular docking is a valuable technique
      in computational chemistry to deeply analyze ligand recognition and has led to
      important breakthroughs in drug discovery and design in the field of beta
      adrenergic receptors.

PMID- 28738773
TI  - Pro-angiogenic Molecules for Therapeutic Angiogenesis.
AB  - BACKGROUND: Therapeutic angiogenesis is a clinical intervention for controlled
      stimulation and augmentation of neovascularisation in ischemic tissues.
      Conventional therapeutic techniques involve proangiogenic factor based induction
      of host tissue angiogenesis. In this review, we provide a holistic idea about
      therapeutic angiogenesis while specifically highlighting the role of
      proangiogenic factors as growth factors, peptides, small molecules and
      polysaccharides in tissue neovascularisation. METHODS: A detailed search of peer
      reviewed literature was carried out with prime focus on therapeutic angiogenesis
      and proangiogenic factors. The content of each literature reviewed in this paper
      was qualitatively analysed for particulars and relevance to the subject of study.
      This work has been distributed under four broad titles, namely, proangiogenic
      growth factors, peptides, small molecules and polysaccharides. Also, recent
      developments pertaining to proangiogenic factors for therapeutic angiogenesis
      have been detailed. RESULTS: A total of 244 literatures have been reviewed from
      the bibliographic database to present a conceptual understanding about the
      importance of proangiogenic factors in revascularisation of ischemic tissues.
      CONCLUSION: This review focuses on importance of various proangiogenic factors,
      with reference to therapeutic angiogenesis. Thorough analysis of clinical data
      reveals the dearth of a defined system for proangiogenic growth factor delivery.
      Designing of a biomaterial based paradigm for growth factor therapy, might help
      in enhancing clinical translation of therapeutic angiogenesis.

PMID- 28738774
TI  - Advanced Methods for the Analysis of Testosterone.
AB  - Testosterone is the principal endogenous androgenic-anabolic steroid in humans.
      The levels of testosterone in the human body are correlated with many hormonal
      disorders (hypogonadism, impotence, etc) mostly in men, and with many types of
      diseases such as: prostate cancer, metabolic syndrome, obesity, cardiovascular
      diseases and so on. Testosterone is extensively used among sportsmen willing to
      increase strength, aggressiveness, and recovery; making it the most commonly
      reported substance in steroid abuse. Fast, easy and cheap methods for the
      evaluation of testosterone are extremely needed in clinics and hospitals. This
      review is dedicated to surveying recent determination methods of testosterone
      from different biological samples such as: serum, saliva, plasma, urine or
      fingernail samples. After a brief description of the role of this steroid hormone
      in the biomedical field, various types of determination methods are described.
      The most important methods are immunoassays, liquid chromatography tandem
      massspectrometry and electrochemical methods. Different types of sensors were
      designed for the rapid assessment of testosterone: immunosensors, biosensors,
      stochastic or multimode sensors. One can conclude that to date, the available
      methods of analysis can cover a wide concentration range, able to detect
      testosterone from children's saliva, where the levels are the lowest (using
      stochastic sensors), to whole blood, where electrochemical, immunological and
      chromatographic methods can be used.

PMID- 28738775
TI  - Autophagy to the Rescue.

PMID- 28738776
TI  - Graph-based Clustering of miRNA Sequences.
AB  - AIMS: The many miRNAs discovered so far have been divided into biologically
      representative families, aiming at organizing and systematizing their study so to
      promote, mainly, a better understanding of their functionalities. Clustering
      miRNA sequences can corroborate the family-based organizations as well as helping
      to explore sequences belonging to the same cluster as potentially having similar
      biological functions. OBSERVATIONS: Considering that members of the same miRNA
      family tend to biologically function in similar ways, a well-structured family
      can help detecting miRNA functions which have not been associated yet with any
      existing family. METHODS: The work described in this paper empirically
      investigates the suitability of organizing miRNAs as families, using a clustering
      algorithm based on a particular type of graph i.e., minimal spanning tree (MST),
      for clustering miRNA sequences. Seven miRNA families stored in the online miRBase
      database have been used as input to the MST-based clustering algorithm and
      clustering results have been compared to assess the suitability of identirying
      them. RESULTS: The motivations for the experiments were to identify refinements
      in miRNA family organizations that could be pursued and, also, investigate how
      the chosen graph-based clustering algorithm would perform in miRNA related
      domains. CONCLUSION: Interesting and useful results, particularly related to
      detecting information based on the visualization of the final induced graphs, and
      their induced connected components (clusters), are presented and discussed.
      Particularly, experiments results suggested the possibility of refining some
      miRNA families by grouping some of their miRNAs as sub-families.

PMID- 28738777
TI  - Aberrantly Binding microRNAs and their Interactions with Nuclear Hormone
      Receptors.
AB  - HISTORY: Nuclear Hormone Receptors (NHRs) are the most important targets that
      play vital role in cellular signaling pathways of disease. Regulation of NHRs by
      using potential non-coding RNAs, miRNA, is clinically important to control a
      disease. However, the detailed status of miRNA interactions with NHRs remains
      unclear. Hence, the focus of the present study is to investigate the interface at
      the genome-wide level in human, mouse and rat using computational biology
      approach. OBSERVATIONS: This big-data analysis explored thousands of available
      miRNAs interactions with the NHRs and the results showed that 11 miRNAs have
      conserved targets, where six miRNAs are genetically conserved among different
      species. This implies that both conserved and non-conserved miRNAs have a
      potential role in NHRs regulation. We found several "Aberrantly Binding miRNAs"
      (ABMs) that can bind to the target NHR genes. In this study, for human miR-548,
      rat miR-Let-7 and miR-30, mouse miR-466 are identified as potential ABMs
      families. We also found the list of genes targeting ABMs. RESULTS: Specifically,
      these miRNAs majorly targeted bind nuclear subfamily receptor genes in all
      studied animal species. ABMs family interaction with NHR genes is favored by AT
      richness and the length of the gene. CONCLUSION: Our findings suggest that,
      specific ABMs family targeting NHRs may act as potential candidates to regulate
      the downstream signaling pathways.

PMID- 28738778
TI  - Cardiac profile of asymptomatic children with Becker and Duchenne muscular
      dystrophy under treatment with steroids and with/without perindopril.
AB  - BACKGROUND: To evaluate cardiovascular function in boys with Duchenne (DMD) and
      Becker (BMD) muscular dystrophy, using cardiac magnetic resonance (CMR). METHODS:
      This is a single point cross sectional study of twenty-four boys with genetically
      ascertained DMD, and 10 with BMD, aged 10.5 +/- 1.5 years (range 9-13), were
      prospectively evaluated by a 1.5 T system and compared with those of age-sex
      matched controls. The DMD patients were divided in 2 groups. Group A (N = 12)
      were under treatment with both deflazacort and perindopril, while Group B (n =
      12) were under treatment with deflazacort, only. BMD patients did not take any
      medication. Biventricular function was assessed using a standard SSFP sequence.
      Late gadolinium enhancement (LGE) was assessed from T1 images taken 15 min after
      injection of 0.2 mg/Kg gadolinium DTPA using a 3D-T1-TFE sequence. RESULTS: Group
      A and BMDs were asymptomatic with normal ECG, 24 h ECG recording and
      echocardiogram. Group B were asymptomatic but 6/12 had abnormal ECG and mildly
      impaired LVEF. Their 24 h ECG recording revealed supraventricular and ventricular
      extrasystoles (all at 12-13 yrs). LV indices in Group A and BMD did not differ
      from those of controls. However, LV indices in Group B were significantly
      impaired compared with controls, Group A and BMDs (p < 0.001). An epicardial LGE
      area = 3 +/- 0.5% of LV mass was identified in the posterolateral wall of LV only
      in 6/12 patients of Group B, but in not in any BMD or Group A. CONCLUSION:
      Children with either BMD or DMD under treatment with both deflazacort and
      perindopril present preserved LV function and lack of LGE. However, further large
      scale multicenter studies are warranted to confirm these data, including further
      CMR mapping approaches.

PMID- 28738779
TI  - Anion-selective Formate/nitrite transporters: taxonomic distribution,
      phylogenetic analysis and subfamily-specific conservation pattern in prokaryotes.
AB  - BACKGROUND: The monovalent anions formate, nitrite and hydrosulphide are main
      metabolites of bacterial respiration during anaerobic mixed-acid fermentation.
      When accumulated in the cytoplasm, these anions become cytotoxic. Membrane
      proteins that selectively transport these monovalent anions across the membrane
      have been identified and they belong to the family of Formate/Nitrite
      Transporters (FNTs). Individual members that selectively transport formate,
      nitrite and hydrosulphide have been investigated. Experimentally determined
      structures of FNTs indicate that they share the same hourglass helical fold with
      aquaporins and aquaglyceroporins and have two constriction regions, namely,
      cytoplasmic slit and central constriction. Members of FNTs are found in bacteria,
      archaea, fungi and protists. However, no FNT homolog has been identified in
      mammals. With FNTs as potential drug targets for many bacterial diseases, it is
      important to understand the mechanism of selectivity and transport across these
      transporters. RESULTS: We have systematically searched the sequence databases and
      identified 2206 FNT sequences from bacteria, archaea and eukaryotes. Although FNT
      sequences are very diverse, homology modeling followed by structure-based
      sequence alignment revealed that nearly one third of all the positions within the
      transmembrane region exhibit high conservation either as a group or at the level
      of individual residues across all three kingdoms. Phylogenetic analysis of
      prokaryotic FNT sequences revealed eight different subgroups. Formate, nitrite
      and hydrosulphide transporters respectively are clustered into two (FocA and
      FdhC), three (NirC-alpha, NirC-beta and NirC-gamma) and one (HSC) subfamilies. We
      have also recognized two FNT subgroups (YfdC-alpha and YfdC-beta) with unassigned
      function. Analysis of taxonomic distribution indicates that each subfamily
      prefers specific taxonomic groups. Structure-based sequence alignment of
      individual subfamily members revealed that certain positions in the two
      constriction regions and some residues facing the interior show subfamily
      specific conservation. We have also identified examples of FNTs with the two
      constriction regions formed by residues that are less frequently observed. We
      have developed dbFNT, a database of FNT models and associated details. dbFNT is
      freely available to scientific community. CONCLUSIONS: Taxonomic distribution and
      sequence conservation of FNTs exhibit subfamily-specific features. The
      conservation pattern in the central constriction and cytoplasmic slit in the open
      and closed states are distinct for YfdC and NirC subfamilies. The same is true
      for some residues facing the interior of the transporters. The specific residues
      in these positions can exert influence on the type of solutes that are
      transported by these proteins. With FNTs found in many disease-causing bacteria,
      the knowledge gained in this study can be used in the development and design of
      anti-bacterial drugs.

PMID- 28738780
TI  - Distinct herpesvirus resistances and immune responses of three gynogenetic clones
      of gibel carp revealed by comprehensive transcriptomes.
AB  - BACKGROUND: Gibel carp is an important aquaculture species in China, and a
      herpesvirus, called as Carassius auratus herpesvirus (CaHV), has hampered the
      aquaculture development. Diverse gynogenetic clones of gibel carp have been
      identified or created, and some of them have been used as aquaculture varieties,
      but their resistances to herpesvirus and the underlying mechanism remain unknown.
      RESULTS: To reveal their susceptibility differences, we firstly performed
      herpesvirus challenge experiments in three gynogenetic clones of gibel carp,
      including the leading variety clone A+, candidate variety clone F and wild clone
      H. Three clones showed distinct resistances to CaHV. Moreover, 8772, 8679 and
      10,982 differentially expressed unigenes (DEUs) were identified from comparative
      transcriptomes between diseased individuals and control individuals of clone A+,
      F and H, respectively. Comprehensive analysis of the shared DEUs in all three
      clones displayed common defense pathways to the herpesvirus infection, activating
      IFN system and suppressing complements. KEGG pathway analysis of specifically
      changed DEUs in respective clones revealed distinct immune responses to the
      herpesvirus infection. The DEU numbers identified from clone H in KEGG immune
      related pathways, such as "chemokine signaling pathway", "Toll-like receptor
      signaling pathway" and others, were remarkably much more than those from clone A+
      and F. Several IFN-related genes, including Mx1, viperin, PKR and others, showed
      higher increases in the resistant clone H than that in the others. IFNphi3, IFI44
      like and Gig2 displayed the highest expression in clone F and IRF1 uniquely
      increased in susceptible clone A+. In contrast to strong immune defense in
      resistant clone H, susceptible clone A+ showed remarkable up-regulation of genes
      related to apoptosis or death, indicating that clone A+ failed to resist virus
      offensive and evidently induced apoptosis or death. CONCLUSIONS: Our study is the
      first attempt to screen distinct resistances and immune responses of three
      gynogenetic gibel carp clones to herpesvirus infection by comprehensive
      transcriptomes. These differential DEUs, immune-related pathways and IFN system
      genes identified from susceptible and resistant clones will be beneficial to
      marker-assisted selection (MAS) breeding or molecular module-based resistance
      breeding in gibel carp.

PMID- 28738781
TI  - The value of a new cardiac magnetic resonance imaging protocol in Myocardial
      Infarction with Non-obstructive Coronary Arteries (MINOCA) - a case-control study
      using historical controls from a previous study with similar inclusion criteria.
AB  - BACKGROUND: Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA)
      is common with a prevalence of 6% of all patients fulfilling the diagnosis of
      myocardial infarction. MINOCA should be considered a working diagnosis. Cardiac
      Magnetic Resonance (CMR) imaging has recently been suggested to be of great value
      to determine the cause behind MINOCA. The objectives of this paper are to
      describe the rationale behind the second Stockholm Myocardial Infarction with
      Normal Coronaries (SMINC-2) study and to discuss the protocol for investigation
      of MINOCA patients in the light of the recently published position paper from the
      European Society of Cardiology. METHODS: The SMINC-2 study is an open non
      randomised study using historical controls for comparison. The primary aim is to
      prove that MINOCA patients investigated with the latest CMR imaging technique can
      achieve a diagnosis in 70% of all cases entirely by imaging. By including 150
      patients we will have >80% chance to prove that the diagnostic accuracy can be
      improved by 20 absolute % with a p-value of less than 0.05 when compared with CMR
      imaging in the SMINC-1 study. Furthermore, in addition to invasive coronary
      angiography, coronary arteries are evaluated by computed tomography angiography
      to investigate coronary causes and questionnaires are used to describe Quality-of
      Life (QoL). By January 1st 2017, 75 patients have been included. DISCUSSION:
      Whether CMR imaging can provide a diagnosis to an adequate proportion of MINOCA
      patients is unknown. Well-defined inclusion and exclusion criteria will be used
      to compare a MINOCA cohort from the population with an appropriate control group.
      Positive results are likely to influence future guidelines of the management of
      MINOCA. Furthermore, the study will give mechanistic insights into MINOCA in
      particular in patients with "true" myocardial infarction and describe QoL in this
      vulnerable group of patients. TRIAL REGISTRATION: Clinical Trials NCT02318498 .

PMID- 28738782
TI  - Space and space-time distributions of dengue in a hyper-endemic urban space: the
      case of Girardot, Colombia.
AB  - BACKGROUND: Dengue is a widely spread vector-borne disease. Dengue cases in the
      Americas have increased over the last few decades, affecting various urban spaces
      throughout these continents, including the tourism-oriented city of Girardot,
      Colombia. Interactions among mosquitoes, pathogens and humans have recently been
      examined using different temporal and spatial scales in attempts to determine the
      roles that social and ecological systems play in dengue transmission. The current
      work characterizes the spatial and temporal behaviours of dengue in Girardot and
      discusses the potential territorial dynamics related to the distribution of this
      disease. METHODS: Based on officially reported dengue cases (2012-2015)
      corresponding to epidemic (2013) and inter-epidemic years (2012, 2014, 2015),
      space (Getis-Ord index) and space-time (Kulldorff's scan statistics) analyses
      were performed. RESULTS: Geocoded dengue cases (n = 2027) were slightly
      overrepresented by men (52.1%). As expected, the cases were concentrated in the 0
      to 15-year-old age group according to the actual trends of Colombia. The
      incidence rates of dengue during the rainy and dry seasons as well as those for
      individual years (2012, 2013 and 2014) were significant using the global Getis
      Ord index. Local clusters shifted across seasons and years; nevertheless, the
      incidence rates clustered towards the southwest region of the city under
      different residential conditions. Space-time clusters shifted from the northeast
      to the southwest of the city (2012-2014). These clusters represented only 4.25%
      of the total cases over the same period (n = 1623). A general trend was observed,
      in which dengue cases increased during the dry seasons, especially between
      December and February. CONCLUSIONS: Despite study limitations related to official
      dengue records and available fine-scale demographic information, the spatial
      analysis results were promising from a geography of health perspective. Dengue
      did not show linear association with poverty or with vulnerable peripheral spaces
      in intra-urban settings, supporting the idea that the pathogenic complex of
      dengue is driven by different factors. A coordinated collaboration of
      epidemiological, public health and social science expertise is needed to assess
      the effect of "place" from a relational perspective in which geography has an
      important role to play.

PMID- 28738783
TI  - Efficacy of coenzyme Q10 in patients with cardiac failure: a meta-analysis of
      clinical trials.
AB  - BACKGROUND: The therapeutic efficacy of coenzyme Q10 on patients with cardiac
      failure remains controversial. We pooled previous clinical studies to re-evaluate
      the efficacy of coenzyme Q10 in patients with cardiac failure. METHODS: We
      searched PubMed, Cochrane Library, EMBASE, and Clinical Trials.gov databases for
      controlled trials. The endpoints were death, left heart ejection fraction,
      exercise capacity, and New York Heart Association (NYHA) cardiac function
      classification after treatment. The pooled risk ratios (RRs) and standardized
      mean difference (SMD) were used to assess the efficacy of coenzyme Q10. RESULTS:
      A total of 14 RCTs with 2149 patients met the inclusion criteria and were
      included in the analysis. Coenzyme Q10 decreased the mortality compared with
      placebo (RR = 0.69; 95% CI = 0.50-0.95; P = 0.02; I 2  = 0%). A greater
      improvement in exercise capacity was established in patients who used coenzyme
      Q10 than in those who used placebo (SMD = 0.62; 95% CI = 0.02-0.30; P = 0.04; I 2
      = 54%). No significant difference was observed in the endpoints of left heart
      ejection fraction between patients who received coenzyme Q10 and the patients in
      whom placebo was administered (SMD = 0.62; 95% CI = 0.02-1.12; P = 0.04; I 2  =
      75%). The two types of treatment resulted in obtaining similar NYHA
      classification results (SMD = -0.70; 95% CI = -1.92-0.51; P = 0.26; I 2  = 89%).
      CONCLUSION: Patients with heart failure who used coenzyme Q10 had lower mortality
      and a higher exercise capacity improvement than the placebo-treated patients with
      heart failure. No significant differences between the efficacy of the
      administration of coenzyme Q10 and placebo in the endpoints of left heart
      ejection fraction and NYHA classification were observed.

PMID- 28738784
TI  - Identification and characterization of suppressor mutants of stop1.
AB  - BACKGROUND: Proton stress and aluminum (Al) toxicity are major constraints
      limiting crop growth and yields on acid soils (pH < 5). In Arabidopsis, STOP1 is
      a master transcription factor that controls the expression of a set of well
      characterized Al tolerance genes and unknown processes involved in low pH
      resistance. As a result, loss-of-function stop1 mutants are extremely sensitive
      to low pH and Al stresses. RESULTS: Here, we report on screens of an ethyl
      methane sulphonate (EMS)-mutagenized stop1 population and isolation of nine
      strong stop1 suppressor mutants, i.e., the tolerant to proton stress (tps)
      mutants, with significantly enhanced root growth at low pH (4.3). Genetic
      analyses indicated these dominant and partial gain-of-function mutants are caused
      by mutations in single nuclear genes outside the STOP1 locus. Physiological
      characterization of the responses of these tps mutants to excess levels of Al and
      other metal ions further classified them into five groups. Three tps mutants also
      displayed enhanced resistance to Al stress, indicating that these tps mutations
      partially rescue the hypersensitive phenotypes of stop1 to both low pH stress and
      Al stress. The other six tps mutants showed enhanced resistance only to low pH
      stress but not to Al stress. We carried out further physiologic and mapping-by
      sequencing analyses for two tps mutants with enhanced resistance to both low pH
      and Al stresses and identified the genomic regions and candidate loci in
      chromosomes 1 and 2 that harbor these two TPS genes. CONCLUSION: We have
      identified and characterized nine strong stop1 suppressor mutants. Candidate loci
      for two tps mutations that partially rescue the hypersensitive phenotypes of
      stop1 to low pH and Al stresses were identified by mapping-by-sequencing
      approaches. Further studies could provide insights into the structure and
      function of TPSs and the regulatory networks underlying the STOP1-mediated
      processes that lead to resistance to low pH and Al stresses in Arabidopsis.

PMID- 28738785
TI  - Admission serum potassium concentration and long-term mortality in patients with
      acute myocardial infarction: results from the MONICA/KORA myocardial infarction
      registry.
AB  - BACKGROUND: Conflicting with clinical practice guidelines, recent studies
      demonstrated that serum potassium concentrations (SPC) of >=4.5 mEq/l were
      associated with increased mortality in patients with acute myocardial infarction
      (AMI). This study examined the association between SPC and long-term mortality
      following AMI in patients recruited from a population-based registry. METHODS:
      Included in the study were 3347 patients with AMI aged 28-74 years consecutively
      hospitalized between 1 January 2000 and 31 December 2008 and followed up until 31
      December 2011. Patients were categorized into five SPC groups (<3.5, 3.5 to <4.0,
      4.0 to <4.5, 4.5 to <5.0, and >=5.0 mEq/l). The outcome of the study was all
      cause mortality. Cox regression models adjusted for risk factors, co-morbidities
      and in-hospital treatment were constructed. RESULTS: In our study population, 249
      patients (7.4%) had a low SPC (<3.5 mEq/l) and 134 (4.0%) patients had a high SPC
      (>=5.0 mEq/l). Patients with SPC of >=5.0 mEq/l had the highest long-term
      mortality (29.9%) and in the adjusted model, their risk of dying was
      significantly increased (HR 1.46, 95% CI 1.03 to 2.07) compared to patients with
      SPC between 4.0 and <4.5 mEq/l. Analyses of increasing observation periods showed
      a trend towards a higher risk of dying in patients with SPC between 4.5 and <5.0
      mEq/l. CONCLUSION: An admission SPC of >=5.0 mEq/l might be associated with an
      increased mortality risk in patients with AMI. Patients with an admission SPC
      between 4.5 and <5.0 mEq/l might have an increased mortality risk in the first
      few years following AMI.

PMID- 28738786
TI  - Atrial time and voltage dispersion are both needed to predict new-onset atrial
      fibrillation in ischemic stroke patients.
AB  - BACKGROUND: Atrial fibrillation (AF) is a known risk factor for ischemic stroke.
      Electrocardiographic predictors of AF in population studies such as the
      Framingham Heart Study, as well as in hypertensive patients have demonstrated a
      predictive value of the P-wave duration for development of AF. QRS vector
      magnitude has had a predictive value in ventricular arrhythmia development. We
      aimed to assess the value of the three-dimensional P-wave vector magnitude and
      its relationship to P-wave duration for prediction of new-onset AF after ischemic
      stroke. METHODS: First-ever ischemic stroke patients without AF at inclusion in
      the Lund Stroke Register were included. Measurements of P wave duration (Pd), QRS
      duration, corrected QT interval, and PQ interval were performed automatically
      using the University of Glasgow 12-lead ECG analysis algorithm. The P-wave vector
      magnitude (Pvm) was calculated automatically as the square root of the sum of the
      squared P-wave magnitudes in leads V6, II and one half of the P-wave amplitude in
      V2 ([Formula: see text]), based on the P-wave magnitude (Pvm) as defined by the
      visually transformed Kors' Quasi-orthogonal method. RESULTS: The median age was
      73 (IQR 63-80) years at stroke onset (135 males, 92 females). Multivariate
      predictors of new-onset atrial fibrillation included age > 65 years,
      hypertension, and Pd/Pvm. A cut-off value of 870 ms/mV gave sensitivity,
      specificity, positive and negative predictive values of 51, 79, 30 and 87%,
      respectively. The Pd/Pvm was the only ECG predictor of AF with a significant
      multivariate hazard ratio of 2.02 (95% CI 1.18 to 3.46, p = 0.010). CONCLUSION: P
      wave dispersion as measured by the Pd/Pvm was the only ECG parameter measured
      which independently predicted subsequent AF identification in a cohort of stroke
      patients. Further prospective studies in larger cohorts are needed to validate
      its clinical usefulness.

PMID- 28738787
TI  - Procalcitonin-guided antibiotic therapy in critically ill adults: a meta
      analysis.
AB  - BACKGROUND: As a novel biomarker of inflammation, procalcitonin (PCT) has proven
      useful to guide antibiotic therapy in intensive care unit (ICU). However, there
      are controversial on mortality. The aim of this study was to evaluate the utility
      of PCT-guided antibiotic therapy in critically ill adults and determine whether
      studies are sufficient. METHODS: A systematic search in PubMed, Embase and
      Cochrane was performed. We included only randomized controlled trials which
      compared the safety and efficacy between PCT-guided or standard antibiotic
      therapy groups in ICU adults. Trial sequential analysis and GARDE approach were
      performed. RESULTS: Fifteen studies met our criteria for inclusion finally, with
      a cumulative number of 5486 ICU patients. There was no difference in 28-day
      mortality between two compared groups (P = 0.626), but significant decreases were
      observed in the duration of antibiotic therapy for the first episode of infection
      (P < 0.001) and length of hospitalization (P = 0.049). No significant deference
      was found in secondary endpoints except total duration of antibiotic therapy (P <
      0.001). TSA revealed that the pooled sample sizes of 28-day mortality and the
      duration of antibiotic therapy for the first episode of infection exceeded the
      estimated required information size, but not the length of hospitalization.
      CONCLUSIONS: PCT-guided therapy is a better and safer algorithm to be applied
      into ICU patients, which appears no effect on 28-day mortality while performing
      preferable utility in reducing the duration of antibiotic therapy for the first
      episode of infection. More studies on these endpoints were not recommended.

PMID- 28738788
TI  - Magnesium sulfate for 6 vs 24 hours post delivery in patients who received
      magnesium sulfate for less than 8 hours before birth: a randomized clinical
      trial.
AB  - BACKGROUND: To compare the benefits of magnesium sulfate for 24 h (h) postpartum
      versus 6 h postpartum in patients who received magnesium sulfate (Mg) for less
      than 8 h before birth. METHODS: A randomized, multicenter, open study was
      conducted between November 2013 and October 2016 in three teaching maternity
      hospitals in Panama. Pregnant women diagnosed with severe pre-eclampsia or pre
      eclampsia with severe features at more than 20 weeks gestation were invited to
      participate. They were randomized to the following groups in a 1:1 ratio: A-
      continue Mg for 24 h after birth (control group); and B- receive Mg for 6 h after
      birth (experimental group). The primary endpoint and variable was seizure
      (eclampsia) in the first 72 h postpartum. RESULTS: During the study period, 284
      patients agreed to participate in the study; 143 were randomized to receive Mg
      for 24 h postpartum and 141 to receive Mg for 6 h postpartum. There were no
      significant differences in the baseline characteristics of the two groups
      studied. There was no eclampsia in the entire population; therefore, there was no
      significant difference in the primary variable. Two secondary variables showed a
      significant difference: time to onset of ambulation, which was 14 h shorter (p =
      0.0001) in the group that received 6 h of postpartum Mg, and time to initiation
      of breastfeeding, which was 11 h earlier (p = 0.0001) in the group that received
      6 h of postpartum Mg. There were not significant differences between the groups
      with respect to total complications or any particular complication. There were no
      cases of maternal death. CONCLUSION: Maintaining Mg for 6 h postpartum is equally
      effective in preventing eclampsia as receiving Mg for 24 h postpartum in patients
      with severe pre-eclampsia who receive less than 8 h of Mg treatment before birth.
      The onset of maternal ambulation and initiation of breastfeeding are faster in
      patients who only receive Mg for 6 h postpartum. TRIAL REGISTRATION: The study
      was registered at clinical-trials.gov, number NCT02317146 . Date of registration:
      December 11, 2014. This study was registered at clinical trials after the
      beginning of recruitment of patients.

PMID- 28738789
TI  - The impact of indigenous cultural identity and cultural engagement on violent
      offending.
AB  - BACKGROUND: Possessing a strong cultural identity has been shown to protect
      against mental health symptoms and buffer distress prompted by discrimination.
      However, no research to date has explored the protective influences of cultural
      identity and cultural engagement on violent offending. This paper investigates
      the relationships between cultural identity/engagement and violent recidivism for
      a cohort of Australian Indigenous people in custody. METHODS: A total of 122
      adults from 11 prisons in the state of Victoria completed a semi-structured
      interview comprising cultural identification and cultural engagement material in
      custody. All official police charges for violent offences were obtained for
      participants who were released from custody into the community over a period of 2
      years. RESULTS: No meaningful relationship between cultural identity and violent
      recidivism was identified. However a significant association between cultural
      engagement and violent recidivism was obtained. Further analyses demonstrated
      that this relationship was significant only for participants with a strong
      Indigenous cultural identity. Participants with higher levels of cultural
      engagement took longer to violently re-offend although this association did not
      reach significance. CONCLUSIONS: For Australian Indigenous people in custody,
      'cultural engagement' was significantly associated with non-recidivism. The
      observed protective impact of cultural engagement is a novel finding in a
      correctional context. Whereas identity alone did not buffer recidivism directly,
      it may have had an indirect influence given its relationship with cultural
      engagement. The findings of the study emphasize the importance of culture for
      Indigenous people in custody and a greater need for correctional institutions to
      accommodate Indigenous cultural considerations.

PMID- 28738790
TI  - Validity and reliability of an adapted arabic version of the long international
      physical activity questionnaire.
AB  - BACKGROUND: The International Physical Actvity Questionnaire (IPAQ) is a
      validated tool for physical activity assessment used in many countries however no
      Arabic version of the long-form of this questionnaire exists to this date. Hence,
      the aim of this study was to cross-culturally adapt and validate an Arabic
      version of the long International Physical Activity Questionnaire (AIPAQ)
      equivalent to the French version (F-IPAQ) in a Lebanese population. METHODS: The
      guidelines for cross-cultural adaptation provided by the World Health
      Organization and the International Physical Activity Questionnaire committee were
      followed. One hundred fifty-nine students and staff members from Saint Joseph
      University of Beirut were randomly recruited to participate in the study. Items
      of the A-IPAQ were compared to those from the F-IPAQ for concurrent validity
      using Spearman's correlation coefficient. Content validity of the questionnaire
      was assessed using factor analysis for the A-IPAQ's items. The physical activity
      indicators derived from the A-IPAQ were compared with the body mass index (BMI)
      of the participants for construct validity. The instrument was also evaluated for
      internal consistency reliability using Cronbach's alpha and Intraclass
      Correlation Coefficient (ICC). Finally, thirty-one participants were asked to
      complete the A-IPAQ on two occasions three weeks apart to examine its test-retest
      reliability. Bland-Altman analyses were performed to evaluate the extent of
      agreement between the two versions of the questionnaire and its repeated
      administrations. RESULTS: A high correlation was observed between answers of the
      F-IPAQ and those of the A-IPAQ, with Spearman's correlation coefficients ranging
      from 0.91 to 1.00 (p < 0.05). Bland-Altman analysis showed a high level of
      agreement between the two versions with all values scattered around the mean for
      total physical activity (mean difference = 5.3 min/week, 95% limits of agreement
      = -145.2 to 155.8). Negative correlations were observed between MET values and
      BMI, independent of age, gender or university campus. The A-IPAQ showed a high
      internal consistency reliability with Cronbach's alpha ranging from 0.769-1.00 (p
      < 0.001) and intraclass correlation coefficient (ICC) ranging from 0.625-0.999 (p
      < 0.001), except for a moderate agreement with the moderate garden/yard activity
      (alpha = 0.682; ICC = 0.518; p < 0.001). The A-IPAQ had moderate-to-good test
      retest reliability for most of its items (ICC ranging from 0.66-0.96; p < 0.001)
      and the Bland-Altman analysis showed a satisfactory agreement between the two
      administrations of the A-IPAQ for total physical activity (mean difference = 99.8
      min/week, 95% limits of agreement = -1105.3; 1304.9) and total vigorous and
      moderate physical activity (mean difference = -29.7 min/week, 95% limits of
      agreement = -777.6; 718.2). CONCLUSION: The modified Arabic version of the IPAQ
      showed acceptable validity and reliability for the assessment of physical
      activity among Lebanese adults. More studies are necessary in the future to
      assess its validity compared to a gold-standard criterion measure.

PMID- 28738791
TI  - Anthropometric indices for non-pregnant women of childbearing age differ widely
      among four low-middle income populations.
AB  - BACKGROUND: Maternal stature and body mass indices (BMI) of non-pregnant women
      (NPW) of child bearing age are relevant to maternal and offspring health. The
      objective was to compare anthropometric indices of NPW in four rural communities
      in low- to low-middle income countries (LMIC). METHODS: Anthropometry and
      maternal characteristics/household wealth questionnaires were obtained for NPW
      enrolled in the Women First Preconception Maternal Nutrition Trial. Body mass
      index (BMI, kg/m2) was calculated. Z-scores were determined using WHO reference
      data. RESULTS: A total of 7268 NPW participated in Equateur, DRC (n = 1741);
      Chimaltenango, Guatemala (n = 1695); North Karnataka, India (n = 1823); and
      Thatta, Sindh, Pakistan (n = 2009). Mean age was 23 y and mean parity 1.5. Median
      (P25-P75) height (cm) ranged from 145.5 (142.2-148.9) in Guatemala to 156.0
      (152.0-160.0) in DRC. Median weight (kg) ranged from 44.7 (39.9-50.3) in India to
      52.7 (46.9-59.8) in Guatemala. Median BMI ranged from 19.4 (17.6-21.9) in India
      to 24.9 (22.3-28.0) in Guatemala. Percent stunted (<-2SD height for age z-score)
      ranged from 13.9% in DRC to 80.5% in Guatemala; % underweight (BMI <18.5) ranged
      from 1.2% in Guatemala to 37.1% in India; % overweight/obese (OW, BMI >=25.0)
      ranged from 5.7% in DRC to 49.3% in Guatemala. For all sites, indicators for
      higher SES and higher age were associated with BMI. Lower SES women were
      underweight more frequently and higher SES women were OW more frequently at all
      sites. Younger women tended to be underweight, while older women tended to be OW.
      CONCLUSIONS: Anthropometric data for NPW varied widely among low-income rural
      populations in four countries located on three different continents. Global
      comparisons of anthropometric measurements across sites using standard reference
      data serve to highlight major differences among populations of low-income rural
      NPW and assist in evaluating the rationale for and the design of optimal
      intervention trials. TRIAL REGISTRATION: ClinicalTrials.gov # NCT01883193 (18
      June 2013, retrospectively registered).

PMID- 28738792
TI  - Functional study of DAND5 variant in patients with Congenital Heart Disease and
      laterality defects.
AB  - BACKGROUND: Perturbations on the Left-Right axis establishment lead to laterality
      defects, with frequently associated Congenital Heart Diseases (CHDs). Indeed, in
      the last decade, it has been reported that the etiology of isolated cases of CHDs
      or cases of laterality defects with associated CHDs is linked with variants of
      genes involved in the Nodal signaling pathway. METHODS: With this in mind, we
      analyzed a cohort of 38 unrelated patients with Congenital Heart Defects that can
      arise from initial perturbations in the formation of the Left-Right axis and 40
      unrelated ethnically matched healthy individuals as a control population. Genomic
      DNA was extracted from buccal epithelial cells, and variants screening was
      performed by PCR and direct sequencing. A Nodal-dependent luciferase assay was
      conducted in order to determine the functional effect of the variant found.
      RESULTS: In this work, we report two patients with a DAND5 heterozygous non
      synonymous variant (c.455G > A) in the functional domain of the DAND5 protein
      (p.R152H), a master regulator of Nodal signaling. Patient 1 presents left
      isomerism, ventricular septal defect with overriding aorta and pulmonary atresia,
      while patient 2 presents ventricular septal defect with overriding aorta, right
      ventricular hypertrophy and pulmonary atresia (a case of extreme tetralogy of
      Fallot phenotype). The functional analysis assay showed a significant decrease in
      the activity of this variant protein when compared to its wild-type counterpart.
      CONCLUSION: Altogether, our results provide new insight into the molecular
      mechanism of the laterality defects and related CHDs, priming for the first time
      DAND5 as one of multiple candidate determinants for CHDs in humans.

PMID- 28738793
TI  - Association between 28 single nucleotide polymorphisms and type 2 diabetes
      mellitus in the Kazakh population: a case-control study.
AB  - BACKGROUND: We evaluated the associations between single nucleotide polymorphisms
      and different clinical parameters related to type 2 diabetes mellitus (T2DM),
      obesity risk, and metabolic syndrome (MS) in a Kazakh cohort. METHODS: A total of
      1336 subjects, including 408 T2DM patients and 928 control subjects, were
      recruited from an outpatient clinic and genotyped for 32 polymorphisms previously
      associated with T2DM and obesity-related phenotypes in other ethnic groups. For
      association studies, the chi-squared test or Fisher's exact test for binomial
      variables were used. Logistic regression was conducted to explore associations
      between the studied SNPs and the risk of developing T2DM, obesity, and MS, after
      adjustments for age and sex. RESULTS: After excluding four SNPs due to Hardy
      Weinberg disequilibrium, significant associations in age-matched cohorts were
      found betweenT2DM and the following SNPs: rs9939609 (FTO), rs13266634 (SLC30A8),
      rs7961581 (TSPAN8/LGR5), and rs1799883 (FABP2). In addition, examination of
      general unmatched T2DM and control cohorts revealed significant associations
      between T2DM and SNPsrs1799883 (FABP2) and rs9939609 (FTO). Furthermore,
      polymorphisms in the FTO gene were associated with increased obesity risk,
      whereas polymorphisms in the FTO and FABP2 genes were also associated with the
      risk of developing MS in general unmatched cohorts. CONCLUSION: We confirmed
      associations between polymorphisms within the SLC30A8, TSPAN8/LGR5, FABP2, and
      FTO genes and susceptibility to T2DM in a Kazakh cohort, and revealed significant
      associations with anthropometric and metabolic traits. In particular, FTO and
      FABP2 gene polymorphisms were significantly associated with susceptibility to MS
      and obesity in this cohort.

PMID- 28738794
TI  - ESCAschool study: trial protocol of an adaptive treatment approach for school-age
      children with ADHD including two randomised trials.
AB  - BACKGROUND: The ESCAschool study addresses the treatment of school-age children
      with attention-deficit/hyperactivity disorder (ADHD) in a large multicentre
      trial. It aims to investigate three interrelated topics: (i) Clinical guidelines
      often recommend a stepped care approach, including different treatment strategies
      for children with mild to moderate and severe ADHD symptoms, respectively.
      However, this approach has not yet been empirically validated. (ii) Behavioural
      interventions and neurofeedback have been shown to be effective, but the
      superiority of combined treatment approaches such as medication plus behaviour
      therapy or medication plus neurofeedback compared to medication alone remains
      questionable. (iii) Growing evidence indicates that telephone-assisted self-help
      interventions are effective in the treatment of ADHD. However, larger randomised
      controlled trials (RCTs) are lacking. This report presents the ESCAschool trial
      protocol. In an adaptive treatment design, two RCTs and additional observational
      treatment arms are considered. METHODS: The target sample size of ESCAschool is
      521 children with ADHD. Based on their baseline ADHD symptom severity, the
      children will be assigned to one of two groups (mild to moderate symptom group
      and severe symptom group). The adaptive design includes two treatment phases
      (Step 1 and Step 2). According to clinical guidelines, different treatment
      protocols will be followed for the two severity groups. In the moderate group,
      the efficacy of telephone-assisted self-help for parents and teachers will be
      tested against waitlist control in Step 1 (RCT I). The severe group will receive
      pharmacotherapy combined with psychoeducation in Step 1. For both groups,
      treatment response will be determined after Step 1 treatment (no, partial or full
      response). In severe group children demonstrating partial response to medication,
      in Step 2, the efficacy of (1) counselling, (2) behaviour therapy and (3)
      neurofeedback will be tested (RCT II). All other treatment arms in Step 2 (severe
      group: no or full response; moderate group: no, partial or full response) are
      observational. DISCUSSION: The ESCAschool trial will provide evidence-based
      answers to several important questions for clinical practice following a stepped
      care approach. The adaptive study design will also provide new insights into the
      effects of additional treatments in children with partial response. TRIAL
      REGISTRATION: German Clinical Trials Register (DRKS) DRKS00008973 . Registered 18
      December 2015.

PMID- 28738795
TI  - Is surgical excision necessary for the treatment of Granulomatous lobular
      mastitis?
AB  - BACKGROUND: We aimed to investigate the role of surgical excision in treating
      granulomatous lobular mastitis. METHODS: We performed a retrospective chart
      review of patients with granulomatous lobular mastitis treated from March 2008 to
      March 2014. We analyzed clinical features and therapeutic modalities and compared
      the patient outcomes based on treatment. RESULTS: During the study period, a
      total of 34 patients were diagnosed with granulomatous lobular mastitis and
      treated. Initial treatments included wide excision (18), oral steroids after
      incision and drainage (14), and antibiotic therapy (2). The patients receiving
      only antibiotic therapy showed no improvement after 1 month and wide excision was
      then performed. Wide excision resulted in nine case of delayed wound healing with
      fistula. These patients were treated with oral steroids for 1.5-5 months, with
      subsequent improvement. Overall, 11 out of 20 patients who had underwent wide
      excision showed improvement without additional treatment. Fourteen patients who
      had initially received oral steroids for 1 to 6 months (average, 2.8 months)
      after incision and drainage showed complete remission. During the median follow
      up period with 45.5 months (range, 22-98 months), six patients (17.6%)
      experienced recurrence. Wide excision group experienced recurrence in five (25%)
      and steroid and drainage group experienced recurrence in one (7.1%). All six
      recurrences responded to additional steroid therapy for average 3.5 months. Most
      wide excision group left extensive breast scarring with deformation that was not
      in steroid and drainage group. CONCLUSIONS: Wide excision resulted high
      recurrence than steroid and drainage group and left extensive scarring. Steroid
      therapy with or without abscess drainage may be the first choice of treatment for
      majority cases with granulomatous lobular mastitis.

PMID- 28738796
TI  - Health profile for Danish adults with activity limitation: a cross-sectional
      study.
AB  - BACKGROUND: Studies have indicated that people with disabilities die earlier and
      may experience a poorer health than the general population. This study
      investigated 31 factors related to health and well-being, health behaviour and
      social relations among Danish adults with activity limitation (AL). METHODS: This
      study was based on data from the Danish Health and Morbidity Survey (DHMS) 2013
      where 25,000 men and women aged 16 years or older were selected randomly from the
      adult Danish population. A total of 14,265 individuals answered the self
      administered questionnaire including 100 questions on health-related quality of
      life, health behaviour, morbidity, consequences of illness and social relations.
      Based on an international standard question on AL, 888 individuals (6%) were
      defined as having profound AL and 4180 (29%) as having some AL. Multiple logistic
      regression analyses were used to analyse the associations between activity
      limitation and 31 indicators of health. The results were presented as relative
      risks 95% confidence intervals. RESULTS: Twenty-eight of 31 indicators showed
      consistently poorer health and well-being, health behaviour and social relations
      among individuals with AL as compared to individuals without AL. The increased
      relative risks were in a range of 7-661% the risk among individuals without AL.
      An example is obesity where RR (95% CI) was 2.07 (1.82-2.37). Only contact with
      internet friends was significantly higher among individuals with AL as compared
      to individuals with no AL. There was no association between alcohol and AL and no
      association between fast food and some AL. CONCLUSION: Danish adults with AL
      experience a poorer health and well-being, and have an unhealthier lifestyle and
      poorer social relations than adults without AL. People with activity limitation
      should be prioritized in public health and efforts done to secure availability
      and flexibility of health care services and primary prevention programs. Policies
      should address accessibility, availability and affordability of health care and
      health behaviour among people with activity limitation.

PMID- 28738797
TI  - Tibiotalocalcaneal (TTC) arthrodesis with reverse PHILOS plate and medial
      cannulated screws with lateral approach.
AB  - BACKGROUND: Tibiotalocalcaneal arthrodesis is most common and effective surgical
      treatment for severe hindfoot pathology, but the fusion rate is often lower than
      the ordinary tibiotalar arthrodesis because of the more serious joint disease
      associated with obvious deformity and osteoporosis. Recent literature describe
      tibiotalocalcaneal arthrodesis with reverse PHILOS plate with good clinical
      outcome result, though some patients non-union, due to eccentric force of the
      plate may be hidden. The purpose of this study was to evaluate clinical outcome
      of the lateral approach for tibiotalocalcaneal (TTC) arthrodesis with reverse
      PHILOS Plate and medial cannulated screw. METHODS: Between Jun, 2013 to April,
      2015 12 patient with hindfoot pathology had TTC arthrodesis with a reverse PHILOS
      plate with medial cannulated screw through a lateral approach with resection of
      the distal fibula and bone graft. Perioperatively observe for wound and
      neurovascular status. Patients were follow-up from post-operative 1, 3, 6 and12
      months, to observation of wound healing, ankle pain, subtalar Joint Fusion,
      internal fixation and ankle function. Ankle function were scored according to the
      American Orthopaedic Foot and Ankle Society(AOFAS) Ankle-Hindfoot Scale system.
      RESULTS: Twelve ankle fusion all patient follow-up, with mean time to surgery
      18.6 months (12-36 month). No cases infection and issue necrosis; one patient
      complaint of lateral foot numbness we observe and follow-up was spontaneously
      recovery after 3 months. After 3 months of operation, no obvious pain of ankle
      joint and internal fixations loose were found. Almost fusion and good axial
      alignment of TTC joint also were found by X-ray and CT examination. After final
      fellow-up of each case, no case complain of pain of ankle joint, good fusion and
      axial alignment of TTC joint were also all found through Terminology. The mean
      American Orthopaedic Foot and Ankle society (AOFAS) score average was 77.5.
      CONCLUSION: TTC arthrodesis with reverse PHILOS Plate and medial cannulated screw
      have advantages of clear incision, effective bone orthopaedic and graft fully
      secure, stable internal fixation, high fusion rate and less complications, can
      effectively correct deformities, alleviate hindfoot pain and improve function,
      and is an effective method of treatment of after severe hindfoot disease. TRIAL
      REGISTRATION: This trial is registered on ClinicalTrials.gov with reference
      number: ID: NCT02977910 . Registered 26 Nov 2016, retrospectively registered.

PMID- 28738798
TI  - Efficacy of sellar opening in the pituitary adenoma resection of transsphenoidal
      surgery influences the degree of tumor resection.
AB  - BACKGROUND: Endonasal transsphenoidal microsurgery is often adopted in the
      resection of pituitary adenoma, and has showed satisfactory treatment and minor
      injuries. It is important to accurately localize sellar floor and properly incise
      the bone and dura matter. METHODS: Fifty-one patients with pituitary adenoma
      undergoing endonasal transsphenoidal microsurgery were included in the present
      study. To identify the scope of sellar floor opening, CT scan of the paranasal
      sinus and MRI scan of the pituitary gland were performed for each subject.
      Intraoperatively, internal carotid artery injury, leakage of cerebrospinal fluid,
      and tumor texture were recorded, and postoperative complications and residual
      tumors were identified. RESULT: The relative size of sellar floor opening
      significantly differed among the pituitary micro-, macro- and giant adenoma
      groups, and between the total and partial tumor resection groups. The ratio of
      sellar floor opening area to maximal tumor area was significantly different
      between the total and partial resection groups. Logistic regression analysis
      revealed that the ratio of sellar floor opening area to the largest tumor area,
      tumor texture, tumor invasion and age were independent prognostic factors. The
      vertical distance between the top point of sellar floor opening and planum
      sphenoidale significantly differed between the patients with and without leakage
      of cerebrospinal fluid. CONCLUSION: These results together indicated that
      relatively insufficient sellar floor opening is a cause of leading to residual
      tumor, and the higher position of the opening and closer to the planum
      sphenoidale are likely to induce the occurrence of leakage of cerebrospinal
      fluid.

PMID- 28738799
TI  - Prevalence of head lice infestation and pediculicidal effect of permethrine
      shampoo in primary school girls in a low-income area in southeast of Iran.
AB  - BACKGROUND: Head lice infestation is a common public health problem that is most
      prevalent in primary school children throughout the world, especially in
      developing countries including different parts of Iran. This study aimed to
      determine the prevalence and risk factors associated with head lice infestation
      and pediculicidal effect of 1% permethrin shampoo in primary schools girls of
      Bashagard County, one of the low socioeconomic areas in southeast of Iran.
      METHODS: In this interventional study six villages with similar demographical
      situations were selected and randomly assigned into intervention and control
      areas. In each area 150 girl students aged 7-12 years were selected randomly and
      screened for head lice infestation by visual scalp examination. In intervention
      area, treatment efficacy of 1% permethrin shampoo was evaluated via re
      examination for infestation after one, two, and three weeks. Pre-tested
      structured questionnaire was used to collect data on socio-demographic and
      associated factors of head lice infestation. RESULTS: The prevalence of head lice
      infestation was 67.3%. There was significant association between head lice
      infestation and school grade, family size, parents' literacy, bathing facilities,
      frequency of hair washing, and use of shared articles (p < 0.05). The
      effectiveness of 1% permethrin shampoo for head lice treatment was 29.2, 68.9,
      and 90.3% after the first, second, and third weeks, respectively. CONCLUSION: The
      head lice infestation is a health problem in primary school girls of Bashagard
      County. Improvement of socioeconomic status and providing appropriate educational
      programs about head lice risk factors and prevention can be effective for
      reduction of infestation in this area. TRIAL REGISTRATION: This trial has been
      registered and approved by Hormozgan University of Medical Sciences ethical
      committee (Trial No.764). Trial registration date: March 17 2014.

PMID- 28738800
TI  - Benchmarked performance charts using principal components analysis to improve the
      effectiveness of feedback for audit data in HIV care.
AB  - BACKGROUND: Feedback tools for clinical audit data that compare site-specific
      results to average performance over all sites can be useful for quality
      improvement. Proposed tools should be simple and clearly benchmark the site's
      performance, so that a relevant action plan can be directly implemented to
      improve patient care services. We aimed to develop such a tool in order to
      feedback data to UK HIV clinics participating in the 2015 British HIV Association
      (BHIVA) audit assessing compliance with the 2011 guidelines for routine
      investigation and monitoring of adult HIV-1- infected individuals. METHODS: HIV
      clinic sites were asked to provide data on a random sample of 50-100 adult
      patients attending for HIV care during 2014 and/or 2015 by completing a self
      audit spreadsheet. Outcomes audited included the proportion of patients with
      recorded resistance testing, viral load monitoring, adherence assessment,
      medications, hepatitis testing, vaccination management, risk assessments, and
      sexual health screening. For each outcome we benchmarked the proportion for a
      specific site against the average performance. We produced performance charts for
      each site using boxplots for the outcomes. We also used the mean and differences
      from the mean performance to produce a dashboard for each site. We used principal
      components analysis to group correlated outcomes and simplify the dashboard.
      RESULTS: The 106 sites included in the study provided information on a total of
      7768 patients. Outcomes capturing monitoring of treatment of HIV-infection showed
      high performance across the sites, whereas testing for hepatitis, and risk
      assessment for cardiovascular disease and smoking, management of flu vaccination,
      sexual health screening, and cervical cytology for women were very variable
      across sites. The principal components analysis reduced the original 12 outcomes
      to four factors that represented HIV care, hepatitis testing, other screening
      tests, and resistance testing. These provided simplified measures of adherence to
      guidelines which were presented as a 4 bar dashboard of performance. CONCLUSION:
      Our dashboard performance charts provide easily digestible visual summaries of
      locally relevant audit data that are benchmarked against the overall mean and can
      be used to improve feedback to HIV services. Feedback from clinicians indicated
      that they found these charts acceptable and useful.

PMID- 28738801
TI  - Charged residues next to transmembrane regions revisited: "Positive-inside rule"
      is complemented by the "negative inside depletion/outside enrichment rule".
AB  - BACKGROUND: Transmembrane helices (TMHs) frequently occur amongst protein
      architectures as means for proteins to attach to or embed into biological
      membranes. Physical constraints such as the membrane's hydrophobicity and
      electrostatic potential apply uniform requirements to TMHs and their flanking
      regions; consequently, they are mirrored in their sequence patterns (in addition
      to TMHs being a span of generally hydrophobic residues) on top of variations
      enforced by the specific protein's biological functions. RESULTS: With statistics
      derived from a large body of protein sequences, we demonstrate that, in addition
      to the positive charge preference at the cytoplasmic inside (positive-inside
      rule), negatively charged residues preferentially occur or are even enriched at
      the non-cytoplasmic flank or, at least, they are suppressed at the cytoplasmic
      flank (negative-not-inside/negative-outside (NNI/NO) rule). As negative residues
      are generally rare within or near TMHs, the statistical significance is sensitive
      with regard to details of TMH alignment and residue frequency normalisation and
      also to dataset size; therefore, this trend was obscured in previous work. We
      observe variations amongst taxa as well as for organelles along the secretory
      pathway. The effect is most pronounced for TMHs from single-pass transmembrane
      (bitopic) proteins compared to those with multiple TMHs (polytopic proteins) and
      especially for the class of simple TMHs that evolved for the sole role as
      membrane anchors. CONCLUSIONS: The charged-residue flank bias is only one of the
      TMH sequence features with a role in the anchorage mechanisms, others apparently
      being the leucine intra-helix propensity skew towards the cytoplasmic side,
      tryptophan flanking as well as the cysteine and tyrosine inside preference. These
      observations will stimulate new prediction methods for TMHs and protein topology
      from a sequence as well as new engineering designs for artificial membrane
      proteins.

PMID- 28738803
TI  - "Blue flags", development of a short clinical questionnaire on work-related
      psychosocial risk factors - a validation study in primary care.
AB  - BACKGROUND: Working conditions substantially influence health, work ability and
      sick leave. Useful instruments to help clinicians pay attention to working
      conditions are lacking in primary care (PC). The aim of this study was to test
      the validity of a short "Blue flags" questionnaire, which focuses on work-related
      psychosocial risk factors and any potential need for contacts and/or actions at
      the workplace. METHODS: From the original"The General Nordic Questionnaire"
      (QPSNordic) the research group identified five content areas with a total of 51
      items which were considered to be most relevant focusing on work-related
      psychosocial risk factors. Fourteen items were selected from the identified
      QPSNordic content areas and organised in a short questionnaire "Blue flags".
      These 14 items were validated towards the 51 QPSNordic items. Content validity
      was reviewed by a professional panel and a patient panel. Structural and
      concurrent validity were also tested within a randomised clinical trial. RESULTS:
      The two panels (n = 111) considered the 14 psychosocial items to be relevant. A
      four-factor model was extracted with an explained variance of 25.2%, 14.9%, 10.9%
      and 8.3% respectively. All 14 items showed satisfactory loadings on all factors.
      Concerning concurrent validity the overall correlation was very strong rs = 0.87
      (p < 0.001).). Correlations were moderately strong for factor one, rs = 0.62 (p <
      0.001) and factor two, rs = 0.74 (p < 0.001). Factor three and factor four were
      weaker, bur still fair and significant at rs = 0.53 (p < 0.001) and rs = 0.41 (p
      < 0.001) respectively. The internal consistency of the whole "Blue flags" was
      good with Cronbach's alpha of 0.76. CONCLUSIONS: The content, structural and
      concurrent validity were satisfactory in this first step of development of the
      "Blue flags" questionnaire. In summary, the overall validity is considered
      acceptable. Testing in clinical contexts and in other patient populations is
      recommended to ensure predictive validity and usefulness.

PMID- 28738802
TI  - Histological and transcriptomic effects of 17alpha-methyltestosterone on
      zebrafish gonad development.
AB  - BACKGROUND: Sex hormones play important roles in teleost ovarian and testicular
      development. In zebrafish, ovarian differentiation appears to be dictated by an
      oocyte-derived signal via Cyp19a1a aromatase-mediated estrogen production.
      Androgens and aromatase inhibitors can induce female-to-male sex reversal,
      however, the mechanisms underlying gonadal masculinisation are poorly understood.
      We used histological analyses together with RNA sequencing to characterise
      zebrafish gonadal transcriptomes and investigate the effects of 17alpha
      methyltestosterone on gonadal differentiation. RESULTS: At a morphological level,
      17alpha-methyltestosterone (MT) masculinised gonads and accelerated
      spermatogenesis, and these changes were paralleled in masculinisation and de
      feminisation of gonadal transcriptomes. MT treatment upregulated expression of
      genes involved in male sex determination and differentiation (amh, dmrt1, gsdf
      and wt1a) and those involved in 11-oxygenated androgen production (cyp11c1 and
      hsd11b2). It also repressed expression of ovarian development and
      folliculogenesis genes (bmp15, gdf9, figla, zp2.1 and zp3b). Furthermore, MT
      treatment altered epigenetic modification of histones in zebrafish gonads.
      Contrary to expectations, higher levels of cyp19a1a or foxl2 expression in
      control ovaries compared to MT-treated testes and control testes were not
      statistically significant during early gonad development (40 dpf). CONCLUSION:
      Our study suggests that both androgen production and aromatase inhibition are
      important for androgen-induced gonadal masculinisation and natural testicular
      differentiation in zebrafish.

PMID- 28738804
TI  - Oncogenic long noncoding RNA landscape in breast cancer.
AB  - BACKGROUND: Few long noncoding RNAs (lncRNAs) that act as oncogenic genes in
      breast cancer have been identified. METHODS: Oncogenic lncRNAs associated with
      tumourigenesis and worse survival outcomes were examined and validated in Gene
      Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Then,
      the potential biological functions and expression regulation of these lncRNAs
      were studied via bioinformatics and genome data analysis. Moreover, progressive
      breast cancer subtype-specific lncRNAs were investigated via high-throughput
      sequencing in our cohort and TCGA validation. To elucidate the mechanisms of the
      regulation of these lncRNAs, genomic alterations from the TCGA, Broad, Sanger and
      BCCRC data, as well as epigenetic modifications from GEO data, were then applied
      and examined to meet this objective. Finally, cell proliferation assays, flow
      cytometry analyses and TUNEL assays were applied to validate the oncogenic roles
      of these lncRNAs in vitro. RESULTS: A cluster of oncogenic lncRNAs that was
      upregulated in breast cancer tissue and was associated with worse survival
      outcomes was identified. These oncogenic lncRNAs are involved in regulating
      immune system activation and the TGF-beta and Jak-STAT signalling pathways.
      Moreover, TINCR, LINC00511, and PPP1R26-AS1 were identified as subtype-specific
      lncRNAs associated with HER-2, triple-negative and luminal B subtypes of breast
      cancer, respectively. The up-regulation of these oncogenic lncRNAs is mainly
      caused by gene amplification in the genome in breast cancer and other solid
      tumours. Finally, the knockdown of TINCR, DSCAM-AS1 or HOTAIR inhibited breast
      cancer cell proliferation, increased apoptosis and inhibited cell cycle
      progression in vitro. CONCLUSIONS: These findings enhance the landscape of known
      oncogenic lncRNAs in breast cancer and provide insights into their roles. This
      understanding may potentially aid in the comprehensive management of breast
      cancer.

PMID- 28738805
TI  - Spatial variability of excess mortality during prolonged dust events in a high
      density city: a time-stratified spatial regression approach.
AB  - BACKGROUND: Dust events have long been recognized to be associated with a higher
      mortality risk. However, no study has investigated how prolonged dust events
      affect the spatial variability of mortality across districts in a downwind city.
      METHODS: In this study, we applied a spatial regression approach to estimate the
      district-level mortality during two extreme dust events in Hong Kong. We compared
      spatial and non-spatial models to evaluate the ability of each regression to
      estimate mortality. We also compared prolonged dust events with non-dust events
      to determine the influences of community factors on mortality across the city.
      RESULTS: The density of a built environment (estimated by the sky view factor)
      had positive association with excess mortality in each district, while
      socioeconomic deprivation contributed by lower income and lower education induced
      higher mortality impact in each territory planning unit during a prolonged dust
      event. Based on the model comparison, spatial error modelling with the 1st order
      of queen contiguity consistently outperformed other models. The high-risk areas
      with higher increase in mortality were located in an urban high-density
      environment with higher socioeconomic deprivation. CONCLUSION: Our model design
      shows the ability to predict spatial variability of mortality risk during an
      extreme weather event that is not able to be estimated based on traditional time
      series analysis or ecological studies. Our spatial protocol can be used for
      public health surveillance, sustainable planning and disaster preparation when
      relevant data are available.

PMID- 28738806
TI  - Financial crisis and income-related inequalities in the universal provision of a
      public service: the case of healthcare in Spain.
AB  - BACKGROUND: The objective of this paper is to analyse whether the recent
      recession has altered health care utilisation patterns of different income groups
      in Spain. METHODS: Based on information concerning individuals 'income and health
      care use, along with health need indicators and demographic characteristics
      (provided by the Spanish National Health Surveys from 2006/07 and 2011/12),
      econometric models are estimated in two parts (mixed logistic regressions and
      truncated negative binominal regressions) for each of the public health services
      studied (family doctor appointments, appointments with specialists,
      hospitalisations, emergencies and prescription drug use). RESULTS: The results
      show that the principle of universal access to public health provision does not
      in fact prevent a financial crisis from affecting certain income groups more than
      others in their utilisation of public health services. CONCLUSIONS: Specifically,
      in relative terms the recession has been more detrimental to low-income groups in
      the cases of specialist appointments and hospitalisations, whereas it has worked
      to their advantage in the cases of emergency services and family doctor
      appointments.

PMID- 28738807
TI  - Sexual violence against female university students in Ethiopia.
AB  - BACKGROUND: Though many women are suffering the consequences of sexual violence,
      only few victims speak out as it is sensitive and prone to stigma. This lack of
      data made it difficult to get full picture of the problem and design proper
      interventions. Thus, the aim of this study was to assess the prevalence and
      factors associated with sexual violence among female students of Wolaita Sodo
      University, south Ethiopia. METHODS: Institution based cross-sectional study was
      conducted among 462 regular female Wolaita Sodo University students on April
      7/2015. Participants were selected by simple random sampling. Data were collected
      by self-administered questionnaire. Data entry and analysis was done by EPI info
      and SPSS statistical packages respectively. Descriptive statistics were done.
      Moreover, bivariate and multivariate analyses were also carried out to identify
      predictors of sexual violence. RESULT: The age of respondents ranged from 18 to
      26 years. Lifetime sexual violence was found to be 45.4%. However, 36.1% and
      24.4% of respondents reported experiencing sexual violence since entering
      university and in the current academic year respectively. Life time sexual
      violence was positively associated with witnessing inter-parental violence as a
      child, rural childhood residence, having regular boyfriend, alcohol consumption
      and having friends who drink regularly; while it was negatively associated with
      discussing sexual issues with parents. CONCLUSION: Sexual violence is a common
      phenomenon among the students. More detailed research has to be conducted to
      develop prevention and intervention strategies.

PMID- 28738808
TI  - Carotid plaque rather than intima-media thickness as a predictor of recurrent
      vascular events in patients with acute ischemic stroke.
AB  - BACKGROUND: To investigate the impacts of carotid plaque and intima-media
      thickness (IMT) on future vascular events (VEs) in the patients with acute
      ischemic stroke. METHODS: A total of 479 consecutive Korean patients with acute
      ischemic stroke were divided into 2 groups according to development of VEs; VE
      group (65.4 +/- 10.9 years) vs no VE group (62.8 +/- 13.2 years). VEs were
      defined as the development of recurrent stroke, coronary events, peripheral
      arterial disease, and death. Clinical, laboratory, and imaging findings were
      compared between the groups. RESULTS: During 105.5 +/- 29.0 months of follow up,
      VEs were developed in 142 patients (29.6%). In univariate analysis, VEs were
      significantly associated with age, gender, diabetes, renal function, lipid
      levels, left ventricular function, carotid plaque or IMT. In multivariate
      analysis, the presence of carotid plaque, diabetes, renal function and male
      gender were independent predictors of future VEs in the patients with ischemic
      stroke, but carotid IMT was not a predictor of future VEs. Event free survival
      was significantly lower in patients with carotid plaque than without carotid
      plaque on Kaplan-Meier analysis (log rank p < 0.001). CONCLUSION: The present
      study demonstrated that diabetes, impaired renal function, male gender, and the
      presence of carotid plaque rather than IMT were independent predictors of future
      VEs in Korean patients with acute ischemic stroke. Active medical management and
      careful monitoring for the development of recurrent VEs are strongly recommended
      in patients with acute ischemic stroke and carotid plaque.

PMID- 28738809
TI  - Surgical frailty assessment: a missed opportunity.
AB  - BACKGROUND: Preoperative frailty predicts adverse postoperative outcomes. Despite
      the advantages of incorporating frailty assessment into surgical settings, there
      is limited research on surgical healthcare professionals' use of frailty
      assessment for perioperative care. METHODS: Healthcare professionals caring for
      patients enrolled at a Canadian teaching hospital were surveyed to assess their
      perceptions of frailty, as well as attitudes towards and practices for frail
      patients. The survey contained open-ended and 5-point Likert scale questions.
      Responses were compared across professions using independent sample t-tests and
      correlations between survey items were analyzed. RESULTS: Nurses and allied
      health professionals were more likely than surgeons to think frailty should play
      a role in planning a patient's care (nurses vs. surgeons p = 0.008, allied health
      vs. surgeons p = 0.014). Very few respondents (17.5%) reported that they 'always
      used' a frailty assessment tool. Results from qualitative data analysis
      identified four main barriers to frailty assessment: institutional, healthcare
      system, professional knowledge, and patient/family barriers. CONCLUSION: Across
      all disciplines, the lack of knowledge about frailty issues was a prominent
      barrier to the use of frailty assessments in practice, despite clinicians'
      understanding that frailty affects their patients' outcomes. Confidence in
      frailty assessment tool use through education and addressing barriers to
      implementation may increase use and improve patient care. Healthcare
      professionals agree that frailty assessments should play a role in perioperative
      care. However, few perform them in practice. Lack of knowledge about frailty is a
      key barrier in the use of frailty assessments and the majority of respondents
      agreed that they would benefit from further training.

PMID- 28738811
TI  - Associations of genetic variation in CASP3 gene with noise-induced hearing loss
      in a Chinese population: a case-control study.
AB  - BACKGROUND: Noise-induced hearing loss (NIHL) is a complex disease caused by
      environmental and genetic risk factors. This study explored the relationship
      between the genetic variations in the CASP gene and the risk of developing NIHL
      among Chinese workers exposed to occupational noise. METHODS: A case-control
      study of 272 NIHL workers and 272 normal-hearing workers matched for age, sex and
      years of noise exposure was conducted. Fifteen single-nucleotide polymorphisms
      (SNP) in the CASP1, CASP3, CASP4, CASP5, CASP6, CASP8, CASP9, CASP10 and CASP14
      genes were genotyped using the polymerase chain reaction-ligase detection
      reaction method. Using conditional logistic regression models, the adjusted odds
      ratios (ORs) and 95% confidence intervals (CIs) of genetic variations associated
      with NIHL risk were calculated. RESULTS: Two SNPs in the CASP3 gene were
      associated with NIHL risk. For rs1049216, TT genotype was associated with a
      decreased risk of NIHL (OR = 0.246, 95% CI = 0.069-0.886) when compared with the
      CC genotype. For rs6948, the AC and CC genotype were associated with a decreased
      NIHL risk (OR = 0.568, 95% CI = 0.352-0.916) compared with AA genotype. There
      were joint effects of working time and CASP3 polymorphisms on NIHL risk (P <
      0.05). CONCLUSIONS: Genetic variations in the CASP3 gene and the joint effects of
      working time and CASP3 polymorphisms may modify the risk of developing NIHL.

PMID- 28738810
TI  - Role of long non-coding RNAs in glucose metabolism in cancer.
AB  - Long-noncoding RNAs (lncRNAs) are a group of transcripts that are longer than 200
      nucleotides and do not code for proteins. However, this class of RNAs plays
      pivotal regulatory roles. The mechanism of their action is highly complex.
      Mounting evidence shows that lncRNAs can regulate cancer onset and progression in
      a variety of ways. They can not only regulate cancer cell proliferation,
      differentiation, invasion and metastasis, but can also regulate glucose
      metabolism in cancer cells through different ways, such as by directly regulating
      the glycolytic enzymes and glucose transporters (GLUTs), or indirectly modulating
      the signaling pathways. In this review, we summarized the role of lncRNAs in
      regulating glucose metabolism in cancer, which will help understand better the
      pathogenesis of malignant tumors. The understanding of the role of lncRNAs in
      glucose metabolism may help provide new therapeutic targets and novel diagnostic
      and prognosis markers for human cancer.

PMID- 28738812
TI  - Effectiveness of trauma team on medical resource utilization and quality of care
      for patients with major trauma.
AB  - BACKGROUND: Trauma is one of the leading causes of death in Taiwan, and its
      medical expenditure escalated drastically. This study aimed to explore the
      effectiveness of trauma team, which was established in September 2010, on medical
      resource utilization and quality of care among major trauma patients. METHODS:
      This was a retrospective study, using trauma registry data bank and inpatient
      medical service charge databases. Study subjects were major trauma patients
      admitted to a medical center in Tainan during 2009 and 2013, and was divided into
      case group (from January, 2011 to August, 2013) and comparison group (from
      January, 2009 to August, 2010). RESULTS: Significant reductions in several items
      of medical resource utilization were identified after the establishment of trauma
      team. In the sub-group of patients who survived to discharge, examination,
      radiology and operation charges declined significantly. The radiation and
      examination charges reduced significantly in the subcategories of ISS = 16 ~ 24
      and ISS > 24 respectively. However, no significant effectiveness on quality of
      care was identified. CONCLUSIONS: The establishment of trauma team is effective
      in containing medical resource utilization. In order to verify the effectiveness
      on quality of care, extended time frame and extra study subjects are needed.

PMID- 28738813
TI  - Efficacy and safety of proprotein convertase subtilisin-kexin type 9 (PCSK9)
      inhibitors, alirocumab and evolocumab, a post-commercialization study.
AB  - BACKGROUND: Efficacy-safety of proprotein convertase subtilisin-kexin type 9
      (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO), have previously been
      evaluated through controlled clinical trials with selective patient groups. Post
      commercially, in 69 patients with heterozygous familial hypercholesterolemia
      (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC)
      lowering on maximal tolerated LDLC therapy, we assessed efficacy and safety of
      ALI and EVO. METHODS: Post-commercially, we started 29 patients on ALI 75 mg, 18
      on ALI 150 mg, and 22 on EVO 140 mg every 2 weeks added to a maximally tolerated
      LDLC-lowering regimen. Since LDLC lowering did not differ between ALI 150 and EVO
      140 mg, ALI 150-EVO 140 data were pooled (ALI-EVO). Changes in LDLC and AHA and
      NIH calculated 10-year CVD risks were assessed. RESULTS: Of the 69 patients, 25
      had HeFH, 25 CVD, and 19 had both. At entry, 23 (33%) took statins and 46 (67%)
      were statin-intolerant. Mean +/- SD and median follow-up were 49 +/- 13 and 49
      weeks on ALI 75 mg, and 37 +/- 12 and 33 weeks on ALI-EVO. In the ALI-EVO group
      (n = 40), median LDLC fell from 165 mg/dl at entry to 70 mg/dl (median - 59%, p <
      .0001). AHA 10-year calculated CVD risk fell from 10.2 to 5.5% (median - 28%, p <
      .0001), and by the NIH calculator from 14.2 to 3.6% (median - 78%, p < .0001). In
      the ALI 75 mg group (n = 29), entry LDLC fell from 115 to 68 mg/dl (median - 39%,
      p < .0001). AHA 10-year calculated CVD risk fell from 11.5 to 7.3% (median - 20%,
      p = .004), and NIH 10-year risk from 12.9 to 5.1% (median 67%, p < .0001).
      Absolute and percent change in LDLC was independent of statin use. There were flu
      like symptoms in 14% of patients. Adverse events did not differ (p > 0.05)
      between ALI 75 mg and ALI-EVO. CONCLUSION: In patients with HeFH and/or CVD, LDLC
      decreased from 115 to 68 mg/dl (39%) on ALI 75 mg with mean follow-up of 49
      weeks, and from 165 to 70 mg/dl (59%) on ALI-EVO over 37 weeks, p < .0001 for
      both. Adverse events were minimal and tolerable. ALI and EVO represent paradigm
      shifts in LDLC lowering.

PMID- 28738814
TI  - An extended model of vesicle fusion at the plasma membrane to estimate protein
      lateral diffusion from TIRF microscopy images.
AB  - BACKGROUND: Characterizing membrane dynamics is a key issue to understand cell
      exchanges with the extra-cellular medium. Total internal reflection fluorescence
      microscopy (TIRFM) is well suited to focus on the late steps of exocytosis at the
      plasma membrane. However, it is still a challenging task to quantify (lateral)
      diffusion and estimate local dynamics of proteins. RESULTS: A new model was
      introduced to represent the behavior of cargo transmembrane proteins during the
      vesicle fusion to the plasma membrane at the end of the exocytosis process. Two
      biophysical parameters, the diffusion coefficient and the release rate parameter,
      are automatically estimated from TIRFM image sequences, to account for both the
      lateral diffusion of molecules at the membrane and the continuous release of the
      proteins from the vesicle to the plasma membrane. Quantitative evaluation on 300
      realistic computer-generated image sequences demonstrated the efficiency and
      accuracy of the method. The application of our method on 16 real TIRFM image
      sequences additionally revealed differences in the dynamic behavior of
      Transferrin Receptor (TfR) and Langerin proteins. CONCLUSION: An automated method
      has been designed to simultaneously estimate the diffusion coefficient and the
      release rate for each individual vesicle fusion event at the plasma membrane in
      TIRFM image sequences. It can be exploited for further deciphering cell membrane
      dynamics.

PMID- 28738815
TI  - Transcription through the eye of a needle: daily and annual cyclic gene
      expression variation in Douglas-fir needles.
AB  - BACKGROUND: Perennial growth in plants is the product of interdependent cycles of
      daily and annual stimuli that induce cycles of growth and dormancy. In conifers,
      needles are the key perennial organ that integrates daily and seasonal signals
      from light, temperature, and water availability. To understand the relationship
      between seasonal cycles and seasonal gene expression responses in conifers, we
      examined diurnal and circannual needle mRNA accumulation in Douglas-fir
      (Pseudotsuga menziesii) needles at diurnal and circannual scales. Using mRNA
      sequencing, we sampled 6.1 * 109 reads from 19 trees and constructed a de novo
      pan-transcriptome reference that includes 173,882 tree-derived transcripts. Using
      this reference, we mapped RNA-Seq reads from 179 samples that capture daily and
      annual variation. RESULTS: We identified 12,042 diurnally-cyclic transcripts,
      9299 of which showed homology to annotated genes from other plant genomes,
      including angiosperm core clock genes. Annual analysis revealed 21,225 circannual
      transcripts, 17,335 of which showed homology to annotated genes from other plant
      genomes. The timing of maximum gene expression is associated with light intensity
      at diurnal scales and photoperiod at annual scales, with approximately half of
      transcripts reaching maximum expression +/- 2 h from sunrise and sunset, and +/-
      20 days from winter and summer solstices. Comparisons with published studies from
      other conifers shows congruent behavior in clock genes with Japanese cedar
      (Cryptomeria), and a significant preservation of gene expression patterns for
      2278 putative orthologs from Douglas-fir during the summer growing season, and
      760 putative orthologs from spruce (Picea) during the transition from fall to
      winter. CONCLUSIONS: Our study highlight the extensive diurnal and circannual
      transcriptome variability demonstrated in conifer needles. At these temporal
      scales, 29% of expressed transcripts show a significant diurnal cycle, and 58.7%
      show a significant circannual cycle. Remarkably, thousands of genes reach their
      annual peak activity during winter dormancy. Our study establishes the fine-scale
      timing of daily and annual maximum gene expression for diverse needle genes in
      Douglas-fir, and it highlights the potential for using this information for
      evaluating hypotheses concerning the daily or seasonal timing of gene activity in
      temperate-zone conifers, and for identifying cyclic transcriptome components in
      other conifer species.

PMID- 28738816
TI  - Disease activity, resilience and health-related quality of life in Chinese
      patients with rheumatoid arthritis: a multi-center, cross-sectional study.
AB  - BACKGROUND: Positive psychological constructs that can moderate or mediate the
      negative impact of disease activity on health-related quality of life (HRQOL) in
      patients with rheumatoid arthritis (RA) have not been explored widely. This study
      aimed to assess the associations of disease activity, resilience with HRQOL and
      the moderating and mediating roles of resilience among Chinese RA patients.
      METHODS: A multi-center, cross-sectional study was conducted in RA inpatients in
      northeast of China. A total 298 subjects completed the Medical Outcomes Study 36
      item Short-Form Health Survey (SF-36) and Ego-Resiliency Scale (ERS) to measure
      HRQOL and resilience. For the SF-36, physical function, physical role limitation,
      bodily pain and general health perception are gathered into physical component
      summary (PCS), while vitality, social functioning, emotional role limitation and
      mental health are gathered into mental component summary (MCS). Disease activity
      was evaluated by the Disease Activity Score 28-C-reactive protein (DAS28-CRP).
      Hierarchical regression analysis was applied to examine the associations of
      disease activity, resilience and the disease activity*resilience interaction with
      PCS and MCS, respectively. Asymptotic and resampling strategies were utilized to
      examine the mediating role of resilience. RESULTS: The mean scores of PCS and MCS
      were 40.67 and 59.14, respectively. Disease activity was negatively associated
      with both PCS and MCS, and resilience was only positively associated with MCS.
      The disease activity*resilience interaction term were significantly associated
      with MCS (beta = 0.144, P = 0.003). The associations between disease activity and
      MCS were gradually reduced in low (1 SD below the mean, beta = -0.369, P <
      0.001), mean (beta = -0.218, P < 0.001) and high (1 SD above the mean, beta = 
      0.068, P = 0.369) groups of resilience. Resilience acted as a partial mediator in
      the disease activity-MCS association (effect size was -0.085, BCa 95% CI: -0.159,
      -0.028). CONCLUSIONS: Disease activity was negatively associated with both
      physical and mental HRQOL, and resilience was only positively associated with
      mental HRQOL. Resilience could attenuate and mediate the association between
      disease activity and mental HRQOL. In addition to controlling disease activity,
      targeted intervention strategies designed for resilience should be strengthened
      to improve the HRQOL of this population.

PMID- 28738817
TI  - Exacerbation of bronchiectasis by Pseudomonas monteilii: a case report.
AB  - BACKGROUND: Pseudomonas spp are important opportunistic and nosocomial pathogens.
      One such species is Pseudomonas monteilii (P. monteilii). It has been described
      as an environmental contaminant and potential pathogen. We identified this
      organism as the causative agent of an exacerbation of bronchiectasis and an
      environmental contaminant in our hospital on two separate occasions. CASE
      PRESENTATION: P. monteilii was the cause of an exacerbation of bronchiectasis in
      a 30-year-old HIV negative male. Patient presented with cough with sputum
      production and exertional dyspnea. The isolate was recovered from a sputum sample
      in significant counts and definitively identified by Matrix-Assisted Laser
      Desorption/Ionisation- Time of Flight Mass Spectrometry (MALDI-TOF MS). He was
      treated with piperacillin-tazobactam and recovered clinically and
      microbiologically. Another two isolates of the organism were contaminants from
      the hospital environment. The three isolates were susceptible to all tested
      antibiotics. Typing by Random amplification of polymorphic DNA (RAPD) found no
      clonal relationship between them. CONCLUSIONS: Less common species of Pseudomonas
      need to be identified accurately. This organism is identified by commonly used
      phenotypic systems as P. putida which may have contributed to a lower reported
      prevalence. P. monteilii is a known environmental contaminant and must also be
      considered as a potential pathogen, particularly in patients with chronic lung
      disease.

PMID- 28738818
TI  - Health-related quality of life and pain in children and adolescents: a school
      survey.
AB  - BACKGROUND: Pain problems are common in children and adolescents. Measures of
      health-related quality of life (HRQoL) can be used to assess children's
      subjective perspectives of pain experience and its impact on their life. The aims
      of the study were to describe HRQoL and the prevalence of pain in a nonclinical
      population of children and adolescents, and to analyze the relationships between
      HRQoL, pain, sex, and age in a sample of children and adolescents aged 8-18
      years. METHODS: This cross-sectional study involved a cluster sample of 20
      randomly selected schools drawn within a region of Norway. The final study sample
      included 1099 children and adolescents. We measured HRQoL using the generic
      questionnaire KIDSCREEN-52 and pain using questions from the Lubeck Pain
      Screening Questionnaire. Multiple regression was used to analyze relationships
      between HRQoL and sex, age, and pain. RESULTS: The response rate was 74%. A large
      percentage of the sample, 60%, reported pain, and girls reported significantly
      more pain than boys, 76% of the girls in the age group 16-18 years reported pain.
      The KIDSCREEN-52 scores differed between girls and boys, and on average, girls
      reported a significantly lower HRQoL than boys on most dimensions. Pain problems
      were associated with lower HRQoL, and older girls were most impaired by pain.
      CONCLUSIONS: The findings from this study indicate that pain problems are highly
      prevalent in children, and more prevalent in girls than in boys. HRQoL was
      impaired for all 10 dimensions of the KIDSCREEN-52 in children with pain. The
      subscales self-perception, psychological well-being, mood, relationship with
      parents, and school environment were most affected.

PMID- 28738819
TI  - Increased biological activity of protein Kinase C gamma is not required in
      Spinocerebellar ataxia 14.
AB  - Spinocerebellar ataxia (SCA) is an autosomal dominant neurodegenerative disorder
      characterized by slowly progressive cerebellar dysfunction. Currently, 42 SCA
      types are known, some of which are caused by CAG repeat expansions, but others
      are caused by point mutations or deletions. Spinocerebellar ataxia type 14
      (SCA14) is caused by missense mutations or deletions in the PRKCG gene, coding
      for protein kinase C gamma (PKCgamma). It is still not well understood how these
      mutations eventually cause Purkinje cell dysfunction and death. Because PKCgamma
      is a well characterized signaling protein highly expressed in Purkinje cells
      SCA14 offers the chance to better understand the pathogenesis of Purkinje cell
      dysfunction and death. Altered biological activity of PKCgamma would be the
      simplest explanation for the disease phenotype. There are indeed indications that
      the enzymatic activity of mutated PKCgamma proteins could be changed. Many
      mutations found in SCA14 families are located in the regulatory C1B and C1A
      domain, while a few mutations are also found in the C2 and in the catalytic C3
      and C4 domains. For many of these mutations an increased enzymatic activity could
      be demonstrated in cell-based assays, but it remains unclear whether there is
      indeed an altered biological activity of the mutated PKCgamma proteins within
      living Purkinje cells. In this study we used the dendritic morphology of
      developing Purkinje cells to detect increased biological activity of PKCgamma
      after expression of different mutated PKCgamma proteins. Our results indicate
      that two out of three known mutations in the catalytic domain of PKCgamma did
      indeed show increased biological activity. On the other hand, none of the five
      tested mutations located in the regulatory C1 or the C2 domain showed an
      increased biological activity. Our findings indicate that SCA14 mutations located
      in different domains of the PRKCG gene cause SCA14 by different mechanisms and
      that an increased constitutive activity of PKCgamma may be one, but cannot be the
      only mechanism to cause disease in SCA14.

PMID- 28738820
TI  - Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced
      inflammation by inhibiting the HMGB1/TLR4/NF-kappaB pathway following
      experimental traumatic brain injury.
AB  - BACKGROUND: Microglial activation and the subsequent inflammatory response in the
      central nervous system play important roles in secondary damage after traumatic
      brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important
      mediator in late inflammatory responses, interacts with transmembrane receptor
      for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to
      activate downstream signaling pathways, such as the nuclear factor (NF)-kappaB
      signaling pathway, leading to a cascade amplification of inflammatory responses,
      which are related to neuronal damage after TBI. Omega-3 polyunsaturated fatty
      acid (omega-3 PUFA) is a commonly used clinical immunonutrient, which has
      antioxidative and anti-inflammatory effects. However, the effects of omega-3 PUFA
      on HMGB1 expression and HMGB1-mediated activation of the TLR4/NF-kappaB signaling
      pathway are not clear. METHODS: The Feeney DM TBI model was adopted to induce
      brain injury in rats. Modified neurological severity scores, brain water content,
      and Nissl staining were employed to determine the neuroprotective effects of
      omega-3 PUFA supplementation. Assessment of microglial activation in lesioned
      sites and protein markers for proinflammatory, such as tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta, IL-6, interferon (IFN)-gamma, and HMGB1 were
      used to evaluate neuroinflammatory responses and anti-inflammation effects of
      omega-3 PUFA supplementation. Immunofluorescent staining and western blot
      analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1
      mediated activation of the TLR4/NF-kappaB signaling pathway to evaluate the
      effects of omega-3 PUFA supplementation and gain further insight into the
      mechanisms underlying the development of the neuroinflammatory response after
      TBI. RESULTS: It was found that omega-3 PUFA supplementation inhibited TBI
      induced microglial activation and expression of inflammatory factors (TNF-alpha,
      IL-1beta, IL-6, and IFN-gamma), reduced brain edema, decreased neuronal
      apoptosis, and improved neurological functions after TBI. We further demonstrated
      that omega-3 PUFA supplementation inhibited HMGB1 nuclear translocation and
      secretion and decreased expression of HMGB1 in neurons and microglia in the
      lesioned areas. Moreover, omega-3 PUFA supplementation inhibited microglial
      activation and the subsequent inflammatory response by regulating HMGB1 and the
      TLR4/NF-kappaB signaling pathway. CONCLUSIONS: The results of this study suggest
      that microglial activation and the subsequent neuroinflammatory response as well
      as the related HMGB1/TLR4/NF-kappaB signaling pathway play essential roles in
      secondary injury after TBI. Furthermore, omega-3 PUFA supplementation inhibited
      TBI-induced microglial activation and the subsequent inflammatory response by
      regulating HMGB1 nuclear translocation and secretion and also HMGB1-mediated
      activation of the TLR4/NF-kappaB signaling pathway, leading to neuroprotective
      effects.

PMID- 28738821
TI  - Quality improvement, implementation, and dissemination strategies to improve
      mental health care for children and adolescents: a systematic review.
AB  - BACKGROUND: Some outcomes for children with mental health problems remain
      suboptimal because of poor access to care and the failure of systems and
      providers to adopt established quality improvement strategies and interventions
      with proven effectiveness. This review had three goals: (1) assess the
      effectiveness of quality improvement, implementation, and dissemination
      strategies intended to improve the mental health care of children and
      adolescents; (2) examine harms associated with these strategies; and (3)
      determine whether effectiveness or harms differ for subgroups based on system,
      organizational, practitioner, or patient characteristics. METHODS: Sources
      included MEDLINE(r), the Cochrane Library, PsycINFO, and CINAHL, from database
      inception through February 17, 2017. Additional sources included gray literature,
      additional studies from reference lists, and technical experts. Two reviewers
      selected relevant randomized controlled trials (RCTs) and observational studies,
      extracted data, and assessed risk of bias. Dual analysis, synthesis, and grading
      of the strength of evidence for each outcome followed for studies meeting
      inclusion criteria. We also used qualitative comparative analysis to examine
      relationships between combinations of strategy components and improvements in
      outcomes. RESULTS: We identified 18 strategies described in 19 studies. Eleven
      strategies significantly improved at least one measure of intermediate outcomes,
      final health outcomes, or resource use. Moderate strength of evidence (from one
      RCT) supported using provider financial incentives such as pay for performance to
      improve the competence with which practitioners can implement evidence-based
      practices (EBPs). We found inconsistent evidence involving strategies with
      educational meetings, materials, and outreach; programs appeared to be successful
      in combination with reminders or providing practitioners with newly collected
      clinical information. We also found low strength of evidence for no benefit for
      initiatives that included only educational materials or meetings (or both), or
      only educational materials and outreach components. Evidence was insufficient to
      draw conclusions on harms and moderators of interventions. CONCLUSIONS: Several
      strategies can improve both intermediate and final health outcomes and resource
      use. This complex and heterogeneous body of evidence does not permit us to have a
      high degree of confidence about the efficacy of any one strategy because we
      generally found only a single study testing each strategy. TRIAL REGISTRATION:
      PROSPERO, CRD42015024759 .

PMID- 28738822
TI  - Cardiac arrest without physical cardiac injury during Nuss repair of pectus
      excavatum.
AB  - BACKGROUND: Cardiac arrest is a lethal complication of Nuss repair of pectus
      excavatum which is strongly related to heart or big vessels injury. A rare case
      developed cardiac arrest without direct cardiac injury during Nuss procedure is
      presented in this article. CASE PRESENTATION: In July 2015, a previously healthy
      18-year-old man undergoing Nuss repair for pectus excavatum developed cardiac
      arrest while the Nuss bar was being inserted into the chest. After successful
      resuscitation and exclusion of direct cardiac injury, the Nuss procedure was
      continued. The patient suffered a second cardiac arrest during rotation of the
      Nuss bar. This time, the patient had poor initial response to resuscitation and
      defibrillation until the retrosternal bar was removed. He ultimately recovered
      well from the episodes of cardiac arrest, but was unable to receive surgical
      correction of his pectus excavatum deformity. CONCLUSIONS: The possible
      mechanisms of cardiac arrest and lessons we can learn from this complication are
      discussed.

PMID- 28738823
TI  - Metformin suppresses cancer initiation and progression in genetic mouse models of
      pancreatic cancer.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause
      of cancer-associated mortality worldwide with an overall five-year survival rate
      less than 7%. Accumulating evidence has revealed the cancer preventive and
      therapeutic effects of metformin, one of the most widely prescribed medications
      for type 2 diabetes mellitus. However, its role in pancreatic cancer is not fully
      elucidated. Herein, we aimed to further study the preventive and therapeutic
      effects of metformin in genetically engineered mouse models of pancreatic cancer.
      METHODS: LSL-KrasG12D/+; Pdx1-Cre (KC) mouse model was established to investigate
      the effect of metformin in pancreatic tumorigenesis suppression; LSL-KrasG12D/+;
      Trp53fl/+; Pdx1-Cre (KPC) mouse model was used to evaluate the therapeutic
      efficiency of metformin in PDAC. Chronic pancreatitis was induced in KC mice by
      peritoneal injection of cerulein. RESULTS: Following metformin treatment,
      pancreatic acinar-to-ductal metaplasia (ADM) and mouse pancreatic intraepithelial
      neoplasia (mPanIN) were decreased in KC mice. Chronic pancreatitis induced a
      stroma-rich and duct-like structure and increased the formation of ADM and mPanIN
      lesions, in line with an increased cytokeratin 19 (CK19)-stained area. Metformin
      treatment diminished chronic pancreatitis-mediated ADM and mPanIN formation. In
      addition, it alleviated the percent area of Masson's trichrome staining, and
      decreased the number of Ki67-positive cells. In KPC mice, metformin inhibited
      tumor growth and the incidence of abdominal invasion. More importantly, it
      prolonged the overall survival. CONCLUSIONS: Metformin inhibited pancreatic
      cancer initiation, suppressed chronic pancreatitis-induced tumorigenesis, and
      showed promising therapeutic effect in PDAC.

PMID- 28738824
TI  - Visibiome: an efficient microbiome search engine based on a scalable, distributed
      architecture.
AB  - BACKGROUND: Given the current influx of 16S rRNA profiles of microbiota samples,
      it is conceivable that large amounts of them eventually are available for search,
      comparison and contextualization with respect to novel samples. This process
      facilitates the identification of similar compositional features in microbiota
      elsewhere and therefore can help to understand driving factors for microbial
      community assembly. RESULTS: We present Visibiome, a microbiome search engine
      that can perform exhaustive, phylogeny based similarity search and
      contextualization of user-provided samples against a comprehensive dataset of 16S
      rRNA profiles environments, while tackling several computational challenges. In
      order to scale to high demands, we developed a distributed system that combines
      web framework technology, task queueing and scheduling, cloud computing and a
      dedicated database server. To further ensure speed and efficiency, we have
      deployed Nearest Neighbor search algorithms, capable of sublinear searches in
      high-dimensional metric spaces in combination with an optimized Earth Mover
      Distance based implementation of weighted UniFrac. The search also incorporates
      pairwise (adaptive) rarefaction and optionally, 16S rRNA copy number correction.
      The result of a query microbiome sample is the contextualization against a
      comprehensive database of microbiome samples from a diverse range of
      environments, visualized through a rich set of interactive figures and diagrams,
      including barchart-based compositional comparisons and ranking of the closest
      matches in the database. CONCLUSIONS: Visibiome is a convenient, scalable and
      efficient framework to search microbiomes against a comprehensive database of
      environmental samples. The search engine leverages a popular but computationally
      expensive, phylogeny based distance metric, while providing numerous advantages
      over the current state of the art tool.

PMID- 28738825
TI  - Broadening measures of success: results of a behavioral health translational
      research training program.
AB  - BACKGROUND: While some research training programs have considered the importance
      of mentoring in inspiring professionals to engage in translational research, most
      evaluations emphasize outcomes specific to academic productivity as primary
      measures of training program success. The impact of such training or mentoring
      programs on stakeholders and local community organizations engaged in
      translational research efforts has received little attention. The purpose of this
      evaluation is to explore outcomes other than traditional academic productivity in
      a translational research graduate certificate program designed to pair graduate
      students and behavioral health professionals in collaborative service-learning
      projects. METHODS: Semi-structured qualitative interviews with scholars,
      community mentors, and academic mentors were conducted regarding a translational
      research program to identify programmatic impacts. Interviews were transcribed
      and coded by the research team to identify salient themes related to programmatic
      outcomes. RESULTS: Results are framed using the Translational Research Impact
      Scale which is organized into three overarching domains of potential impact: (1)
      research-related impacts, (2) translational impacts, and (3) societal impacts.
      This evaluation demonstrates the program's impact in all three domains of the
      TRIS evaluation framework. Graduate certificate participants (scholars) reported
      that gaining experience in applied behavioral health settings added useful skills
      and expertise to their present careers and increased their interest in pursuing
      translational research. Scholars also described benefits resulting from networks
      gained through participation in the program, including valuable ties between the
      university and community behavioral health organizations. CONCLUSIONS: This
      evaluation of the outcomes of a graduate certificate program providing training
      in translational research highlights the need for more community-oriented and
      practice-based measures of success. Encouraging practitioner involvement in
      translational research is vital to translate knowledge into practice and to
      enable practice-based needs to inform research and policy. A more flexible
      approach to measuring programmatic success in research training programs can help
      bridge the knowledge translation gap.

PMID- 28738826
TI  - Association of adult tobacco use with household food access insecurity: results
      from Nepal demographic and health survey, 2011.
AB  - BACKGROUND: Food insecurity is a very common problem in developing countries
      particularly among the poorer households. Very few studies have tested the
      association between adult smoking and food insecurity. METHODS: We analysed the
      data from a nationally representative sample of 10,826 households in which women
      and men (in a sub sample of 4121 households) aged 15-49 years were interviewed in
      Nepal Demographic and Health Survey 2011. Data from households in which both men
      and women were interviewed were analysed for association of household food
      insecurity access score (HFIAS), with tobacco use among men and women, socio
      demographic and spatial factors. Univariate comparisons followed by zero-inflated
      negative binomial regression analyses were done to determine the association
      between HFIAS and individual, household and spatial factors. RESULTS: Mean HFIAS
      score was 3.5 (SD, 4.6) whereas the median was 0 (IQR 0-6). Prevalence of tobacco
      use among men and women was 50.2% (95% CIs 47.9, 52.6), and 17.3% (95% CIs 15.7,
      18.9). HFIAS scores were significantly higher among households where men used
      tobacco (4.96), and men either smoked or use SLT (3.82) as compared to those
      without tobacco users (2.79). HFIAS scores were not significantly different by
      tobacco use status of women. HFIAS score was highest in the poorest households
      and vice versa. After adjusting for covariates association between HFIAS score
      and male tobacco use remained significant but effect size decreased when
      covariates were included into regression models (adjusted OR 1.11). HFIAS score
      was also associated wealth index (adjusted OR 0.86-0.62) and ecological region
      (adjusted OR 1.33) and development regions (adjusted OR 1.10-1.21). CONCLUSION:
      Tobacco users in poor(er) households should be encouraged to 'quit' their habit.
      Less affluent sectors of the population also need to be educated about the non
      health benefits of quitting, such as improved economic status and reduced food
      insecurity.

PMID- 28738827
TI  - Bacterial tail anchors can target to the mitochondrial outer membrane.
AB  - BACKGROUND: During the generation and evolution of the eukaryotic cell, a
      proteobacterial endosymbiont was re-fashioned into the mitochondrion, an
      organelle that appears to have been present in the ancestor of all present-day
      eukaryotes. Mitochondria harbor proteomes derived from coding information located
      both inside and outside the organelle, and the rate-limiting step toward the
      formation of eukaryotic cells may have been development of an import apparatus
      allowing protein entry to mitochondria. Currently, a widely conserved translocon
      allows proteins to pass from the cytosol into mitochondria, but how proteins
      encoded outside of mitochondria were first directed to these organelles at the
      dawn of eukaryogenesis is not clear. Because several proteins targeted by a
      carboxyl-terminal tail anchor (TA) appear to have the ability to insert
      spontaneously into the mitochondrial outer membrane (OM), it is possible that
      self-inserting, tail-anchored polypeptides obtained from bacteria might have
      formed the first gate allowing proteins to access mitochondria from the cytosol.
      RESULTS: Here, we tested whether bacterial TAs are capable of targeting to
      mitochondria. In a survey of proteins encoded by the proteobacterium Escherichia
      coli, predicted TA sequences were directed to specific subcellular locations
      within the yeast Saccharomyces cerevisiae. Importantly, TAs obtained from DUF883
      family members ElaB and YqjD were abundantly localized to and inserted at the
      mitochondrial OM. CONCLUSIONS: Our results support the notion that eukaryotic
      cells are able to utilize membrane-targeting signals present in bacterial
      proteins obtained by lateral gene transfer, and our findings make plausible a
      model in which mitochondrial protein translocation was first driven by tail
      anchored proteins. REVIEWERS: This article was reviewed by Michael Ryan and
      Thomas Simmen.

PMID- 28738828
TI  - Unraveling multifaceted contributions of small regulatory RNAs to
      photomorphogenic development in Arabidopsis.
AB  - BACKGROUND: Post-transcriptional control of gene expression mediated by small
      regulatory RNAs (sRNAs) is vital for growth and development of diverse organisms.
      The biogenesis of sRNAs is regulated by both positive and negative regulators
      known to regulate photomorphogenic development. Two microRNAs (miRNAs), miR157
      and miR319, also regulate photomorphogenesis. However, genome-wide profiling of
      sRNAs and their regulation of target genes during photomorphogenesis has been
      missing. We provide a comprehensive view of sRNA-controlled gene expression in
      this developmental process. RESULTS: By profiling sRNAs and the 5' ends of
      degraded mRNAs during the first 24 h of photomorphogenic development in
      Arabidopsis, we identified 335 sRNA-mediated mRNA cleavage events in de
      etiolating seedlings. These cleavage events are primarily resulted from actions
      of highly expressed miRNAs and irrelevant to the abundance of target mRNAs. In
      the light, the expression of the slicer protein gene ARGONAUTE1 in the miRNA
      functioning pathway could be fine-tuned by miRNA168a/b. We also found that
      miR396a/b positively regulates de-etiolation by suppressing GROWTH REGULATING
      FACTORs. Our results suggest that the miRNAs are required to tune down the target
      mRNAs and regulate photomorphogenesis. CONCLUSION: sRNAs may have a broad impact
      on gene expression regulation for optimized photomorphogenic development. With
      both positive and negative regulators under the control of sRNAs, young
      Arabidopsis seedlings can have a timely but not exaggerated developmental
      adaptation to light.

PMID- 28738829
TI  - Rare association of two cardiovascular malformations successfully corrected in a
      single surgery: a case report.
AB  - BACKGROUND: Partial anomalous pulmonary venous connection (PAPVC) without an
      atrial septal defect (ASD) associated with coarctation of the aortic arch is a
      rare congenital cardiac anomaly. This rare combination is only described in a few
      studies; none report the correction of these two malformations in a single
      surgery. CASE PRESENTATION: A 5-year-old girl was admitted to our hospital
      because the echocardiography revealed coarctation of the aortic arch; this
      diagnosis was confirmed by computed tomography (CT), which also showed her left
      superior pulmonary vein draining into the vertical vein without ASD (Fig. 1). She
      exhibited no special clinical symptoms. Her upper-limb blood pressure was
      approximately 110/90 mmHg, whereas her lower-limb blood pressure was
      approximately 75/50 mmHg. CONCLUSIONS: We surgically repaired the case of PAPVC
      to the vertical vein with aortic coarctation, in which the two cardiovascular
      malformations were corrected in a single surgery without cardiopulmonary bypass.

PMID- 28738830
TI  - Resampling-based tests for Lasso in genome-wide association studies.
AB  - BACKGROUND: Genome-wide association studies involve detecting association between
      millions of genetic variants and a trait, which typically use univariate
      regression to test association between each single variant and the phenotype.
      Alternatively, Lasso penalized regression allows one to jointly model the
      relationship between all genetic variants and the phenotype. However, it is
      unclear how to best conduct inference on the individual Lasso coefficients,
      especially in high-dimensional settings. METHODS: We consider six methods for
      testing the Lasso coefficients: two permutation (Lasso-Ayers, Lasso-PL) and one
      analytic approach (Lasso-AL) to select the penalty parameter for type-1-error
      control, residual bootstrap (Lasso-RB), modified residual bootstrap (Lasso-MRB),
      and a permutation test (Lasso-PT). Methods are compared via simulations and
      application to the Minnesota Center for Twins and Family Study. RESULTS: We show
      that for finite sample sizes with increasing number of null predictors, Lasso-RB,
      Lasso-MRB, and Lasso-PT fail to be viable methods of inference. However, Lasso-PL
      and Lasso-AL remain fast and powerful tools for conducting inference with the
      Lasso, even in high-dimensions. CONCLUSION: Our results suggest that the proposed
      permutation selection procedure (Lasso-PL) and the analytic selection method
      (Lasso-AL) are fast and powerful alternatives to the standard univariate analysis
      in genome-wide association studies.

PMID- 28738831
TI  - Outcomes after the surgery for acquired nonaccommodative esotropia.
AB  - BACKGROUND: To analyze the surgical outcomes for patients diagnosed with acquired
      nonaccommodative esotropia (ANAET). METHODS: In this retrospective study, the
      medical records of 35 patients who had undergone the surgery for ANAET with a
      postoperative follow-up period of 6 months or more were reviewed. The main
      outcome measures were postoperative esodeviation angle, final success rate, and
      factors affecting surgical outcome. Surgical success was considered to be an
      alignment within 8 prism diopters (PD) at distance and near. RESULTS: The
      preoperative mean esodeviation angles were 37.3 +/- 13.7 PD at distance and 38.6
      +/- 16.6 PD at near. The postoperative mean esodeviation angles at distance were
      as follows: 4.2 PD at day 1, 4.0 PD at month 1, 3.9 PD at month 3, 4.9 PD at
      month 6, 4.7 PD at year 1, and 4.8 PD at final follow-up. There was no
      statistically significant difference in angle of esodeviation between the initial
      postoperative period (day 1 to month 6) and the final follow-up day (p > 0.05).
      The surgical success rate at final follow-up was 65.7% (23/35). Among the 12
      patients for whom the surgery failed, 9 (24.3%) showed esotropia and 3 (8.1%)
      exotropia of more than 8 PD. Six patients (16.2%) underwent reoperation (4 for
      esotropia and 2 for exotropia). There was no factor influencing surgical outcome
      (p > 0.05). CONCLUSIONS: The surgical outcome in patients with ANAET was
      relatively favorable: the final success rate was 65.7% and the reoperation rate
      was 17.1%.

PMID- 28738832
TI  - Systematic mapping review of the factors influencing physical activity and
      sedentary behaviour in ethnic minority groups in Europe: a DEDIPAC study.
AB  - BACKGROUND: Physical activity and sedentary behaviour are associated with health
      and wellbeing. Studies indicate that ethnic minority groups are both less active
      and more sedentary than the majority population and that factors influencing
      these behaviours may differ. Mapping the factors influencing physical activity
      and sedentary behaviour among ethnic minority groups living in Europe can help to
      identify determinants of physical activity and sedentary behaviour, research gaps
      and guide future research. METHODS: A systematic mapping review was conducted to
      map the factors associated with physical activity and sedentary behaviour among
      ethnic minority groups living in Europe (protocol PROSPERO ID = CRD42014014575).
      Six databases were searched for quantitative and qualitative research published
      between 1999 and 2014. In synthesizing the findings, all factors were sorted and
      structured into clusters following a data driven approach and concept mapping.
      RESULTS: Sixty-three articles were identified out of 7794 returned by the
      systematic search. These included 41 quantitative and 22 qualitative studies. Of
      these 58 focused on physical activity, 5 on both physical activity and sedentary
      behaviour and none focused on sedentary behaviour. The factors associated with
      physical activity and sedentary behaviour were grouped into eight clusters.
      Social & cultural environment (n = 55) and Psychosocial (39) were the clusters
      containing most factors, followed by Physical environment & accessibility (33),
      Migration context (15), Institutional environment (14), Social & material
      resources (12), Health and health communication (12), Political environment (3).
      An important finding was that cultural and religious issues, in particular those
      related to gender issues, were recurring factors across the clusters. CONCLUSION:
      Physical activity and sedentary behaviour among ethnic minority groups living in
      Europe are influenced by a wide variety of factors, especially informed by
      qualitative studies. More comparative studies are needed as well as inclusion of
      a wider spectrum of the diverse ethnic minority groups resettled in different
      European countries. Few studies have investigated factors influencing sedentary
      behaviour. It is important in the future to address specific factors influencing
      physical activity and sedentary behaviour among different ethnic minority groups
      in order to plan and implement effective interventions.

PMID- 28738833
TI  - Anxiety and depression among infertile women: a cross-sectional survey from
      Hungary.
AB  - BACKGROUND: Infertility is often associated with a chronic state of stress which
      may manifest itself in anxiety-related and depressive symptoms. The aim of our
      study is to assess the psychological state of women with and without fertility
      problems, and to investigate the background factors of anxiety-related and
      depressive symptoms in women struggling with infertility. METHODS: Our study was
      conducted with the participation of 225 (134 primary infertile and 91 fertile)
      women, recruited in a clinical setting and online. We used the following
      questionnaires: Spielberger Trait Anxiety Inventory (STAI-T), Shortened Beck
      Depression Inventory (BDI) and Fertility Problem Inventory (FPI). We also
      interviewed our subjects on the presence of other sources of stress (the quality
      of the relationship with their mother, financial and illness-related stress), and
      we described sociodemographic and fertility-specific characteristics. We tested
      our hypotheses using independent-samples t-tests (M +/- SD) and multiple linear
      regression modelling (beta). RESULTS: Infertile women were younger (33.30 +/-
      4.85 vs. 35.74 +/- 5.73, p = .001), but had significantly worse psychological
      well-being (BDI = 14.94 +/- 12.90 vs. 8.95 +/- 10.49, p < .0001; STAI-T = 48.76
      +/- 10.96 vs. 41.18 +/- 11.26, p < .0001) than fertile subjects. Depressive
      symptoms and anxiety in infertile women were associated with age, social concern,
      sexual concern and maternal relationship stress. Trait anxiety was also
      associated with financial stress. Our model was able to account for 58% of the
      variance of depressive symptoms and 62% of the variance of trait anxiety.
      CONCLUSIONS: Depressive and anxiety-related symptoms of infertile women are more
      prominent than those of fertile females. The measurement of these indicators and
      the mitigation of underlying distress by adequate psychosocial interventions
      should be encouraged.

PMID- 28738834
TI  - The value of 99mTc-methylene diphosphonate single photon emission computed
      tomography/computed tomography in diagnosis of fibrous dysplasia.
AB  - BACKGROUND: Fibrous dysplasia (FD) is a rare benign bone disorder in which the
      normal bone is replaced by immature fibro-osseous tissue. However, some case
      reports have reported that FD showed significantly increased 99mTc-methylene
      diphosphonate (99mTc-MDP) uptake on whole-body bone scintigraphy (WBS), which may
      mimic bone metastasis or skeletal involvement of the patients with known cancer.
      Thus, the purpose of present study is to observe the reliable characteristics and
      usefulness of single photon emission computed tomography/computed tomography
      (SPECT/CT) for the diagnosis of FD. METHODS: This was a retrospective review of
      21 patients with FD (14 males and 7 females, mean age 51.2 +/- 12.5 years) who
      were referred to have WBS to determine whether there was any osseous metastasis.
      WBS and SPECT/CT images were independently interpreted by two experienced nuclear
      medicine physician together with a diagnostic radiologist. In cases of
      discrepancy, consensus was obtained by a joint reading. The final diagnosis was
      based on biopsy proof and radiologic follow-up over at least 1 year. RESULTS: The
      lesions of FD were most frequently found in craniofacial region (15/21). Eighteen
      of the 21 (85.7%) cases showed moderate and high metabolism on WBS (compared to
      sternum). On CT imaging, GGO and expansion were the most common finding, were
      noted in 90.5% and 85.7% of the patients. Lytic lesions were present in 61.9% of
      the patients, and sclerosis was present in 38.1% of the patients. Cortical
      disruption was not seen in any patient. CONCLUSIONS: FD has certain
      characteristic appearance on SPECT/CT. It should be enrolled in the differential
      diagnoses when lesions show elevated 99mTc-MDP uptake on WBS. For SPECT/CT, the
      CT features of GGO and expansion in the areas of abnormal radiotracer uptake are
      helpful for the diagnosis of FD.

PMID- 28738835
TI  - Incidence of and risk factors for nephrolithiasis in patients with gout and the
      general population, a cohort study.
AB  - BACKGROUND: Nephrolithiasis (NL) is known to be associated with gout, although
      there are few comparative studies on risk and risk factors for NL in gout
      compared to population cohorts. In this cohort study we investigated: (1) overall
      incidence of NL in gout (cases) and general population controls; (2) risk and
      risk factors (common comorbidities and medications) for first-time NL in cases
      and controls separately. METHODS: Cases (n = 29,968) and age-matched and sex
      matched controls (n = 138,678) were identified from the regional healthcare
      database in western Sweden (VEGA). The analyzed risk factors (comorbidities and
      current medication use) for first-time NL, and socioeconomic factors were
      retrieved from VEGA and other national Swedish registers. For cases, follow up
      began on 1 January 2006 or on the first diagnosis of gout if this occurred later,
      and for controls on their index patient's first diagnosis of gout. Follow up
      ended on death, emigration or 31 December 2012. Incidence rates (IR) per 1000
      person-years and hazard ratios (HR) were calculated. The incidence calculations
      were performed for cases (regardless of prior NL) and their controls. HRs with
      first occurrence of NL as outcome were calculated only in those without previous
      NL. RESULTS: In cases there were 678 NL events (IR: 6.16 events per 1000 person
      years (95% CI: 5.70-6.64) and in controls 2125 NL events (IR 3.85 events per 1000
      person-years (95% CI: 3.69-4.02), resulting in an age-sex-adjusted incidence rate
      ratio of 1.60 (95% CI:1.47-1.74). Point estimates for predictive factors were
      similar in cases and controls, except for a significant interaction for losartan
      which increased the risk of NL only in controls (HR = 1.49 (95% CI: 1.03-2.14).
      Loop diuretics significantly decreased the risk of NL by 30-34% in both cases and
      controls. Further significant predictors of NL in gout cases were male sex,
      diabetes and obesity and in controls male sex and kidney disease. CONCLUSIONS:
      The risk (age and sex adjusted) of NL was increased by 60% in cases compared to
      controls. None of the commonly used medications increased the risk of NL in gout
      patients.

PMID- 28738836
TI  - Metabolism-associated danger signal-induced immune response and reverse immune
      checkpoint-activated CD40+ monocyte differentiation.
AB  - Adaptive immunity is critical for disease progression and modulates T cell (TC)
      and antigen-presenting cell (APC) functions. Three signals were initially
      proposed for adaptive immune activation: signal 1 antigen recognition, signal 2
      co-stimulation or co-inhibition, and signal 3 cytokine stimulation. In this
      article, we propose to term signal 2 as an immune checkpoint, which describes
      interactions of paired molecules leading to stimulation (stimulatory immune
      checkpoint) or inhibition (inhibitory immune checkpoint) of an immune response.
      We classify immune checkpoint into two categories: one-way immune checkpoint for
      forward signaling towards TC only, and two-way immune checkpoint for both forward
      and reverse signaling towards TC and APC, respectively. Recently, we and others
      provided evidence suggesting that metabolic risk factors (RF) activate innate and
      adaptive immunity, involving the induction of immune checkpoint molecules. We
      summarize these findings and suggest a novel theory, metabolism-associated danger
      signal (MADS) recognition, by which metabolic RF activate innate and adaptive
      immunity. We emphasize that MADS activates the reverse immune checkpoint which
      leads to APC inflammation in innate and adaptive immunity. Our recent evidence is
      shown that metabolic RF, such as uremic toxin or hyperhomocysteinemia, induced
      immune checkpoint molecule CD40 expression in monocytes (MC) and elevated serum
      soluble CD40 ligand (sCD40L) resulting in CD40+ MC differentiation. We propose
      that CD40+ MC is a novel pro-inflammatory MC subset and a reliable biomarker for
      chronic kidney disease severity. We summarize that CD40:CD40L immune checkpoint
      can induce TC and APC activation via forward stimulatory, reverse stimulatory,
      and TC contact-independent immune checkpoints. Finally, we modeled metabolic RF
      induced two-way stimulatory immune checkpoint amplification and discussed
      potential signaling pathways including AP-1, NF-kappaB, NFAT, STAT, and DNA
      methylation and their contribution to systemic and tissue inflammation.

PMID- 28738837
TI  - Assessment of cerebral circulation in a porcine model of intravenously given E.
      coli induced fulminant sepsis.
AB  - BACKGROUND: The aim of the present work was to assess cerebral hemodynamic
      changes in a porcine model of E.coli induced fulminant sepsis. METHODS: Nineteen
      healthy female Hungahib pigs, 10-12 weeks old, randomly assigned into two groups:
      Control (n = 9) or Septic Group (n = 10). In the Sepsis group Escherichia coli
      culture suspended in physiological saline was intravenously administrated in a
      continuously increasing manner according to the following protocol: 2 ml of
      bacterial culture suspended in physiological saline was injected in the first 30
      min, then 4 ml of bacterial culture was administered within 30 min, followed by
      infusion of 32 ml bacterial culture for 2 h. Control animals received identical
      amount of saline infusion. Systemic hemodynamic parameters were assessed by PiCCo
      monitoring, and cerebral hemodynamics by transcranial Doppler sonography
      (transorbital approach) in both groups. RESULTS: In control animals, systemic
      hemodynamic variables and cerebral blood flow velocities and pulsatility indices
      were relatively stable during the entire procedure. In septic animals shock
      developed in 165 (IQR: 60-255) minutes after starting the injection of E.coli
      solution. Blood pressure values gradully decreased, whereas pulse rate increased.
      A decrease in cardiac index, an increased systemic vascular resistance, and an
      increased stroke volume variation were observed. Mean cerebral blood flow
      velocity in the middle cerebral artery did not change during the procedure, but
      pulsatility index significantly increased. CONCLUSIONS: There is vasoconstriction
      at the level of the cerebral arterioles in the early phase of experimental sepsis
      that overwhelmes autoregulatory response. These results may serve as additional
      pathophysiological information on the cerebral hemodynamic changes occurring
      during the septic process and may contribute to a better understanding of the
      pathomechanism of septic encephalopathy.

PMID- 28738838
TI  - Improved detection of genus-specific Alphavirus using a generic TaqMan(r) assay.
AB  - BACKGROUND: Alphaviruses are arthropod borne RNA viruses of medical importance.
      Geographical expansion of mosquitoes of the Aedes genus in the past decades has
      been associated with major Alphavirus-associated outbreaks. Climate changes and
      intensification of air travels have favored vector expansion and virus
      dissemination in new territories leading to virus emergence not only in tropical
      areas but also in temperate regions. The detection of emergence is based upon
      surveillance networks with epidemiological and laboratory investigation. METHOD:
      A specific, sensitive and rapid screening test for genus-specific Alphavirus is
      critically required. To address this issue, we developed a new molecular assay
      targeting nsP4 gene and using a TaqMan(r) real time RT-PCR method for the
      specific detection of all major Alphavirus genus members. RESULTS: This assay was
      tested for specificity using several Alphavirus species. We also tested
      successfully clinical sensitivity using patient's samples collected during the
      Chikungunya outbreak of 2005-2006 in the Indian Ocean. CONCLUSIONS: This new pan
      Alphavirus molecular diagnostic tool offers great potential for exclusion
      diagnosis and emergence detection given its broad specificity restricted to
      Alphavirus genus.

PMID- 28738839
TI  - Evolution of metabolic alterations 5 Years after early puberty in a cohort of
      girls predisposed to polycystic ovary syndrome.
AB  - BACKGROUND: We and others have observed that young girls predisposed to
      polycystic ovary syndrome (PCOS) display defective insulin sensitivity, beta-cell
      function and non-esterified fatty acids (NEFA) suppressibility during early
      pubertal years, compared to controls. Our objective is to assess whether these
      differences in glucose and NEFA metabolisms persist after 5 years in late/post
      puberty. METHODS: We conducted a prospective cohort study between 2007 and 2015
      with 4-6 years of follow-up in an academic institution research center. We
      compared 8 daughters and sisters of PCOS women (PCOSr) to 8 age-matched girls
      unrelated to PCOS (+/-1.5 years). Girls were assessed initially at 8-14 years old
      and re-assessed after a median follow-up of 5.4 years, at 13-21 years old. Our
      main measures were a frequently sampled intravenous glucose tolerance test
      (FSivGTT)-derived insulin sensitivity (IS) and beta-cell function (disposition
      index, DIFSivGTT); and indices of NEFA suppression during FSivGTT (logn-linear
      slope of NEFA and T50 of NEFA suppression). RESULTS: At follow-up, both PCOSr and
      controls had similar results: IS = 3.2 vs 3.4 (p = 0.88), DIFSivGTT = 1926 vs
      1380 (p = 0.44), logn-linear slope = -0.032 vs -0.032 (p = 0.88) and T50NEFA =
      18.1 vs 20.8 min (p = 0.57). IS, DIFSivGTT and NEFA suppressibility were stable
      in PCOSr after 5 years, but decreased significantly in controls (all p < 0.05).
      CONCLUSIONS: Impaired metabolism observed during early puberty in girls
      predisposed to PCOS remains stable after 5 years whereas control girls
      deteriorated their metabolic parameters. Therefore, both groups become comparable
      in late/post-puberty. Early puberty may thus represent a window during which
      metabolic alterations are transiently apparent in girls at risk of PCOS.

PMID- 28738840
TI  - Progress towards malaria elimination in Zimbabwe with special reference to the
      period 2003-2015.
AB  - BACKGROUND: An intensive effort to control malaria in Zimbabwe has produced
      dramatic reductions in the burden of the disease over the past 13 years. The
      successes have prompted the Zimbabwe's National Malaria Control Programme to
      commit to elimination of malaria. It is critical to analyse the changes in the
      morbidity trends based on surveillance data, and scrutinize reorientation to
      strategies for elimination. METHODS: This is a retrospective study of available
      Ministry of Health surveillance data and programme reports, mostly from 2003 to
      2015. Malaria epidemiological data were drawn from the National Health
      Information System database. Data on available resources, malaria control
      strategies, morbidity and mortality trends were analysed, and opportunities for
      Zimbabwe malaria elimination agenda was perused. RESULTS: With strong government
      commitment and partner support, the financial gap for malaria programming shrank
      by 91.4% from about US$13 million in 2012 to US$1 million in 2015. Vector control
      comprises indoor residual house spraying (IRS) and long-lasting insecticidal
      nets, and spray coverage increased from 28% in 2003 to 95% in 2015. Population
      protected by IRS increased also from 20 to 96% for the same period. In 2009,
      diagnostics improved from clinical to parasitological confirmation either by
      rapid diagnostic tests or microscopy. Artemisinin-based combination therapy was
      used to treat malaria following chloroquine resistance in 2000, and sulfadoxine
      pyrimethamine in 2004. In 2003, there were 155 malaria cases per 1000 populations
      reported from all health facilities throughout the country. The following decade
      witnessed a substantial decline in cases to only 22 per 1000 populations in 2012.
      A resurgence was reported in 2013 (29/1000) and 2014 (39/1000), thereafter
      morbidity declined to 29 cases per 1000 populations, only to the same level as in
      2013. Overall, morbidity declined by 81% from 2003 to 2015. Inpatient malaria
      deaths per 100,000 populations doubled in 4 years, from 2/100,000 to 4/100,000
      populations in 2012-2015 respectively. Twenty of the 47 moderate to high burdened
      districts were upgraded from control to malaria pre-elimination between 2012 and
      2015. CONCLUSIONS: A significant progress to reduce malaria transmission in
      Zimbabwe has been made. While a great potential and opportunities to eliminate
      malaria in the country exist, elimination is not a business as usual approach.
      Instead, it needs an improved, systematic and new programmatic strategy supported
      strongly by political will, sustained funding, good leadership, community
      engagement, and a strong monitoring and evaluation system all year round until
      the cessation of local transmission.

PMID- 28738841
TI  - Identifying and mitigating batch effects in whole genome sequencing data.
AB  - BACKGROUND: Large sample sets of whole genome sequencing with deep coverage are
      being generated, however assembling datasets from different sources inevitably
      introduces batch effects. These batch effects are not well understood and can be
      due to changes in the sequencing protocol or bioinformatics tools used to process
      the data. No systematic algorithms or heuristics exist to detect and filter batch
      effects or remove associations impacted by batch effects in whole genome
      sequencing data. RESULTS: We describe key quality metrics, provide a freely
      available software package to compute them, and demonstrate that identification
      of batch effects is aided by principal components analysis of these metrics. To
      mitigate batch effects, we developed new site-specific filters that identified
      and removed variants that falsely associated with the phenotype due to batch
      effect. These include filtering based on: a haplotype based genotype correction,
      a differential genotype quality test, and removing sites with missing genotype
      rate greater than 30% after setting genotypes with quality scores less than 20 to
      missing. This method removed 96.1% of unconfirmed genome-wide significant SNP
      associations and 97.6% of unconfirmed genome-wide significant indel associations.
      We performed analyses to demonstrate that: 1) These filters impacted variants
      known to be disease associated as 2 out of 16 confirmed associations in an AMD
      candidate SNP analysis were filtered, representing a reduction in power of 12.5%,
      2) In the absence of batch effects, these filters removed only a small proportion
      of variants across the genome (type I error rate of 3%), and 3) in an independent
      dataset, the method removed 90.2% of unconfirmed genome-wide SNP associations and
      89.8% of unconfirmed genome-wide indel associations. CONCLUSIONS: Researchers
      currently do not have effective tools to identify and mitigate batch effects in
      whole genome sequencing data. We developed and validated methods and filters to
      address this deficiency.

PMID- 28738842
TI  - Ovarian preservation in adenocarcinoma of the uterine cervix.
AB  - BACKGROUND: An upward trending incidence in cervical adenocarcinoma (ADC) has
      been reported in many countries. Because non-squamous histology has been
      associated with increased risk of ovarian metastases (OM), bilateral oophorectomy
      is commonly performed for ADC without due consideration for ovarian preservation,
      degrading the quality of life for young premenopausal patients. METHODS: Subjects
      were patients with International Federation of Gynecology and Obstetrics (FIGO)
      stage I-IIB cervical ADC who underwent radical hysterectomy, including pelvic
      lymphadenectomy and bilateral salpingo-oophorectomy at our institution between
      Oct. 2006 and Sept. 2014. Clinicopathologic variables were studied by univariate
      and multivariate analyses. RESULTS: Of the 312 patients enrolled in the study, 14
      patients (4.5%) developed OM. Multivariate analysis revealed that uterine corpus
      involvement (odds ratio [OR] 5.178, p = 0.019), parametrial involvement (OR
      14.125, p = 0.005) and vaginal infiltration (OR 4.167, p = 0.047) were
      independently associated with metastasis. OM had no effect on either relapse-free
      survival (95% confidence interval [CI]: 0.077-4.095, p = 0.57) or overall
      survival (95% CI: 0.893-9.820, p = 0.076). CONCLUSION: Cervical ADC is associated
      with an increased risk of OM. Ovarian preservation surgery in cervical ADC may be
      safe for young patients at an early FIGO stage without deep stromal, endometrial
      or perineural invasion, and particularly without uterine corpus invasion,
      parametrial involvement and infiltration into the vagina.

PMID- 28738843
TI  - Astaxanthin mitigates cobalt cytotoxicity in the MG-63 cells by modulating the
      oxidative stress.
AB  - BACKGROUND: With the re-popularity of metal-on-metal (MoM) bearing in recent
      years, the cobalt toxicity has been a cause for concern in the total hip
      replacement surgery by both physicians and patients. METHODS: MG-63 cell line was
      cultured in vitro and incubated with cobalt (II) chloride (CoCl2) and/or with
      astaxanthin (ASX) for 24 h. MTT assay was conducted to evaluate the cell
      viability after cobalt exposure and ASX treatment. Fluorescence-activated cell
      sorting (FACS) analysis was performed to examine the reactive oxygen species
      (ROS) level. Quantitative real-time polymerase chain reaction (PCR) was adopted
      to determine the mRNA levels of related targets. And western blot analysis was
      used to examine the protein expressions. One-way ANOVA with posttest Newman-Keuls
      multiple comparisons was adopted to analysis all the obtained data. RESULTS: In
      the current study, ASX exhibited significant protective effect against the Co(II)
      induced cytotoxicity in MG-63 cell line. We also found that ASX protected the
      cells against Co-induced apoptosis by regulating the expression of Bcl-2 family
      proteins. Besides, heme oxygenase 1 (HO-1) could be activated by Co exposure; ASX
      treatment significantly inhibited HO-1 activation, suppressing the oxidative
      stress induced by Co exposure. Moreover, c-Jun N-terminal Kinase (JNK)
      phosphorylation was shown to participate in the signaling pathway of the
      protective effect of ASX. However, knockdown of JNK expression by siRNA
      transfection or JNK inhibitor SP600125 treatment did not affect the protective
      effect of ASX against cobalt cytotoxicity in MG-63 cells. CONCLUSIONS: ASX
      mitigated cobalt cytotoxicity in the MG-63 cells by modulating the oxidative
      stress. And ASX could be a promising therapy against cobalt toxicity in the hip
      articulation surgery.

PMID- 28738844
TI  - Analysis of SDHAF3 in familial and sporadic pheochromocytoma and paraganglioma.
AB  - BACKGROUND: Germline mutations in genes encoding subunits of succinate
      dehydrogenase (SDH) are associated with the development of pheochromocytoma (PC)
      and/or paraganglioma (PGL). As assembly factors have been identified as playing a
      role in maturation of individual SDH subunits and assembly of the functioning SDH
      complex, we hypothesized that SDHAF3 variants may be associated with PC/PGL and
      functionality of SDH. METHODS: DNA was extracted from the blood of 37 individuals
      (from 23 families) with germline SDH mutations and 18 PC/PGL (15 sporadic, 3
      familial) and screened for mutations using a custom gene panel, containing SDHAF3
      (SDH assembly factor 3) as well as eight known PC/PGL susceptibility genes.
      Molecular and functional consequences of an identified sequence variant of SDHAF3
      were assessed in yeast and mammalian cells (HEK293). RESULTS: Using massively
      parallel sequencing, we identified a variant in SDHAF3, c.157 T > C (p.Phe53Leu),
      associated with increased prevalence in familial and sporadic PC/PGL (6.6%) when
      compared to normal populations (1.2% [1000 Genomes], p = 0.003; 2.1% [Exome
      Aggregation Consortium], p = 0.0063). In silico prediction tools suggest this
      variant is probably damaging to protein function, hence we assessed molecular and
      functional consequences of the resulting amino acid change (p.Phe53Leu) in yeast
      and human cells. We showed that introduction of SDHAF3 p.Phe53Leu into Sdh7
      (ortholog of SDHAF3 in humans) null yeast resulted in impaired function, as
      observed by its failure to restore SDH activity when expressed in Sdh7 null yeast
      relative to WT SDHAF3. As SDHAF3 is involved in maturation of SDHB, we tested the
      functional impact of SDHAF3 c.157 T > C and various clinically relevant SDHB
      mutations on this interaction. Our in vitro studies in human cells show that
      SDHAF3 interacts with SDHB (residues 46 and 242), with impaired interaction
      observed in the presence of the SDHAF3 c.157 T > C variant. CONCLUSIONS: Our
      studies reveal novel insights into the biogenesis of SDH, uncovering a vital
      interaction between SDHAF3 and SDHB. We have shown that SDHAF3 interacts directly
      with SDHB (residue 242 being key to this interaction), and that a variant in
      SDHAF3 (c.157 T > C [p.Phe53Leu]) may be more prevalent in individuals with
      PC/PGL, and is hypomorphic via impaired interaction with SDHB.

PMID- 28738845
TI  - Lutein and zeaxanthin isomers modulates lipid metabolism and the inflammatory
      state of retina in obesity-induced high-fat diet rodent model.
AB  - BACKGROUND: Several studies associated high-fat intakes with a high incidence of
      age-related macular degeneration (AMD). Lutein and Zeaxanthin isomers (L/Zi) may
      counteract reactive oxygen species produced by oxidative stress. The present
      study was conducted to determine the possible effects of L/Zi administration on
      lipid profile, protein genes associated with oxidative stress and inflammation
      pathways in the obesity induced by a high-fat diet (HFD) in rodents. METHODS:
      Twenty-eight male Wistar rats were allocated into four groups as follows: (i)
      Control, (ii) Control + L/Zi, (iii) High Fat Diet (HFD), and (iv) HFD+ L/Z. L/Zi
      was administrated for 8 weeks at a daily dose of 100 mg/kg BW. RESULTS: L/Zi
      administration significantly reduced insulin and free fatty acid (FFA) levels (P
      < 0.001) and ameliorated the oxidative damage by reducing malondialdehyde (MDA)
      concentration and increasing antioxidant enzymes activities of retina induced by
      HFD. In addition, supplementation decreased the levels of vascular endothelial
      growth factor (VEGF), inducible nitric oxide synthase (iNOS), nuclear factor
      kappa B (NF-kappaB) and intercellular adhesion molecule-1 (ICAM) (P < 0.001,
      respectively) and improved nuclear factor erythroid 2-related factor 2 (Nrf2) and
      heme oxygenase 1 (HO-1) gene proteins in retinal tissues (P < 0.001). CONCLUSION:
      Rats fed with HFD exhibited increased oxidative stress and upregulation of
      inflammatory indicators. However, L/Zi supplementation modulates genes involved
      oxidative stress and inflammation including NF-kappaB and Nrf2 signaling pathways
      in the retina which may contribute to ameliorating retinal damage induced by HFD.

PMID- 28738846
TI  - Long non-coding RNAs as novel players in beta cell function and type 1 diabetes.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) are a sub-class within non-coding RNA
      repertoire that have emerged as crucial regulators of the gene expression in
      various pathophysiological conditions. lncRNAs display remarkable versatility and
      wield their functions through interactions with RNA, DNA, or proteins.
      Accumulating body of evidence based on multitude studies has highlighted the role
      of lncRNAs in many autoimmune and inflammatory diseases, including type 1
      diabetes (T1D). This review highlights emerging roles of lncRNAs in immune and
      islet beta cell function as well as some of the challenges and opportunities in
      understanding the pathogenesis of T1D and its complications. CONCLUSION: We
      accentuate that the lncRNAs within T1D-loci regions in consort with regulatory
      variants and enhancer clusters orchestrate the chromatin remodeling in beta cells
      and thereby act as cis/trans-regulatory determinants of islet cell
      transcriptional programs.

PMID- 28738848
TI  - Influence of borderline cefepime MIC on the outcome of cefepime-susceptible
      Pseudomonas aeruginosa bacteremia treated with a maximal cefepime dose: a
      hospital-based retrospective study.
AB  - BACKGROUND: We assessed the influence of current cefepime minimal inhibitory
      concentration (MIC) breakpoints and the maximal cefepime dose on treatment
      outcomes in patients with bacteremia caused by cefepime-susceptible Pseudomonas
      aeruginosa. METHODS: Adult patients hospitalized between July 2010 and June 2014
      with a positive blood culture for cefepime-susceptible P. aeruginosa and receipt
      of cefepime as the primary therapy throughout the course were reviewed. Cefepime
      Etest(r) MICs and clinical outcomes for P. aeruginosa bacteremia were reviewed to
      identify the MIC breakpoint influencing treatment outcomes. RESULTS: Of the 90
      patients enrolled, 49 (54.4%) were male (mean age = 66.8 years). The mean Acute
      Physiology and Chronic Health Evaluation II score was 22.01. Sixty patients
      (66.7%) received a maximal cefepime dose, and the 30-day crude mortality rate was
      36.7%. MIC90 of cefepime for P. aeruginosa was 8 mg/L. The cumulative survival
      rate at 30 days revealed that a lower cefepime MIC (<4 mg/L) for P. aeruginosa
      was associated with a higher survival rate than a higher MIC (>=4 mg/L) (72.6%
      vs. 23.5%, p < 0.0001). A cefepime MIC of >=4 mg/L and age were independent risk
      factors for mortality, whereas the maximal cefepime dose was the independent
      protective factor. The use of a maximal cefepime dose did not improve the
      outcomes of patients with P. aeruginosa bacteremia at a MIC of >=4 mg/L.
      CONCLUSIONS: A cefepime MIC of 4 mg/L may predict an unfavorable outcome among
      patients with serious infections caused by P. aeruginosa, even the MICs still
      within the CLSI susceptibility breakpoint.

PMID- 28738847
TI  - Longitudinal genomic surveillance of multidrug-resistant Escherichia coli
      carriage in a long-term care facility in the United Kingdom.
AB  - BACKGROUND: Residents of long-term care facilities (LTCF) may have high carriage
      rates of multidrug-resistant pathogens, but are not currently included in
      surveillance programmes for antimicrobial resistance or healthcare-associated
      infections. Here, we describe the value derived from a longitudinal
      epidemiological and genomic surveillance study of drug-resistant Escherichia coli
      in a LTCF in the United Kingdom (UK). METHODS: Forty-five of 90 (50%) residents
      were recruited and followed for six months in 2014. Participants were screened
      weekly for carriage of extended-spectrum beta-lactamase (ESBL) producing E. coli.
      Participants positive for ESBL E. coli were also screened for ESBL-negative E.
      coli. Phenotypic antibiotic susceptibility of E. coli was determined using the
      Vitek2 instrument and isolates were sequenced on an Illumina HiSeq2000
      instrument. Information was collected on episodes of clinical infection and
      antibiotic consumption. RESULTS: Seventeen of 45 participants (38%) carried ESBL
      E. coli. Twenty-three of the 45 participants (51%) had 63 documented episodes of
      clinical infection treated with antibiotics. Treatment with antibiotics was
      associated with higher risk of carrying ESBL E. coli. ESBL E. coli was mainly
      sequence type (ST)131 (16/17, 94%). Non-ESBL E. coli from these 17 cases was more
      genetically diverse, but ST131 was found in eight (47%) cases. Whole-genome
      analysis of 297 ST131 E. coli from the 17 cases demonstrated highly related
      strains from six participants, indicating acquisition from a common source or
      person-to-person transmission. Five participants carried highly related strains
      of both ESBL-positive and ESBL-negative ST131. Genome-based comparison of ST131
      isolates from the LTCF study participants with ST131 associated with bloodstream
      infection at a nearby acute hospital and in hospitals across England revealed
      sharing of highly related lineages between the LTCF and a local hospital.
      CONCLUSIONS: This study demonstrates the power of genomic surveillance to detect
      multidrug-resistant pathogens and confirm their connectivity within a healthcare
      network.

PMID- 28738849
TI  - Immune suppression of IgG response against dairy proteins in major depression.
AB  - BACKGROUND: Interactions between the digestive system, brain functions and
      immunoglobulin G (IgG) mediated immunity against food antigens became recently a
      topic of growing interest in psychiatry research. Psychological stress can
      activate hypothalamic-pituitary-adrenal axis (HPA) with subsequent
      hypercortisolemia. It can also influence intestinal permeability and dynamics of
      IgG response. Major depression can by accompanied either by activation of
      inflammatory response or by immune suppression (e.g. decreased antibody
      production) where hypercortisolemia is a significant immune modulator. The aim of
      our study was to assess IgG immune response against 44 food products in depressed
      patients and controls along with markers of psychological stress, inflammation,
      psychometric and dietary parameters. METHODS: Serum IgG concentrations against 44
      food antigens, plasma cortisol, TNF-alpha, IL-6, IL-1b concentrations were
      measured and psychometric parameters were evaluated using Hamilton Depression
      Rating (HAM-D 17), Perceived Stress (PSS-10), and Symptom Checklist (SCL-90)
      scales in 34 depressed patients and 29 controls. Dietary parameters such as
      frequency of exposure to food antigens, appetite and weight change were assessed.
      RESULTS: There was a significantly lower IgG concentration against dairy in
      depressed patients compared to controls (post hoc p < 0.05) when there was a high
      exposure (consumption) to dairy. Our research revealed a significant interaction
      of IgG concentration against dairy proteins and exposure to dairy between groups
      (F (2.63) = 3.92, p = 0.025, eta2 = 0.12). There was no significant difference in
      mean IgG concentration against food antigens between patients and controls. We
      found increased concentration of cortisol in depressed patients (t (1.61) = 2.37,
      p = 0.02) compared to controls. Patients with melancholic depression had
      significantly higher (M rank  = 21.27) concentration of cortisol (U = 41, p =
      0.006), when compared with the non-melancholic group of patients (M rank  =
      12.16). Cortisol concentration significantly positively correlated with HAM-D 17
      (r = 0.442, p = 0.009) and with phobias in SCL-90 scale in patients' group (r =
      0.531, p = 0.001). There was decreased concentration of TNF-alpha (t = 4.256, p <
      0.001) in depressed patients compared to controls. IgG concentration of 38.63%
      food products positively correlated with TNF-alpha concentration in depressed
      patients compared to 9.09% of those in healthy controls. CONCLUSIONS: We observed
      an immune suppression of IgG response to dairy proteins in depressed patients.
      Hypercortisolemia with involvement of decreased concentration of TNF-alpha might
      play a significant role in suppression of IgG response in depressed patients.

PMID- 28738850
TI  - Brain biomarkers and pre-injury cognition are associated with long-term cognitive
      outcome in children with traumatic brain injury.
AB  - BACKGROUND: Children with traumatic brain injury (TBI) are frequently at risk of
      long-term impairments of attention and executive functioning but these problems
      are difficult to predict. Although deficits have been reported to vary with
      injury severity, age at injury and sex, prognostication of outcome remains
      imperfect at a patient-specific level. The objective of this proof of principle
      study was to evaluate a variety of patient variables, along with six brain
      specific and inflammatory serum protein biomarkers, as predictors of long-term
      cognitive outcome following paediatric TBI. METHOD: Outcome was assessed in 23
      patients via parent-rated questionnaires related to attention deficit
      hyperactivity disorder (ADHD) and executive functioning, using the Conners 3rd
      Edition Rating Scales (Conners-3) and Behaviour Rating Inventory of Executive
      Function (BRIEF) at a mean time since injury of 3.1 years. Partial least squares
      (PLS) analyses were performed to identify factors measured at the time of injury
      that were most closely associated with outcome on (1) the Conners-3 and (2) the
      Behavioural Regulation Index (BRI) and (3) Metacognition Index (MI) of the BRIEF.
      RESULTS: Higher levels of neuron specific enolase (NSE) and lower levels of
      soluble neuron cell adhesion molecule (sNCAM) were associated with higher scores
      on the inattention, hyperactivity/impulsivity and executive functioning scales of
      the Conners-3, as well as working memory and initiate scales of the MI from the
      BRIEF. Higher levels of NSE only were associated with higher scores on the
      inhibit scale of the BRI. CONCLUSIONS: NSE and sNCAM show promise as reliable,
      early predictors of long-term attention-related and executive functioning
      problems following paediatric TBI.

PMID- 28738852
TI  - Tertiary syphilis in the lumbar spine: a case report.
AB  - BACKGROUND: The incidence of tertiary syphilis involvement in the spinal column
      with destructive bone lesions is very rare. It is difficult to establish the
      correct diagnosis from radiographs and histological examination alone. Limited
      data are available on surgical treatment to tertiary syphilitic spinal lesions.
      In this article, we report a case of tertiary syphilis in the lumbar spine with
      osteolytic lesions causing cauda equina compression. CASE PRESENTATION: A 44-year
      old man who suffered with low back pain for 6 months and progressive radiating
      pain at lower extremity for 1 week. Radiologic findings showed osteolytic lesion
      and new bone formation in the parts of the bodies of L4 and L5. Serum treponema
      pallidum hemagglutination (TPHA) test was positive. A surgery of posterior
      debridement, interbody and posterolateral allograft bone fusion with
      instrumentation from L3 to S1 was performed. The low back pain and numbness
      abated after operation. But the follow-up radiographs showed absorption of the
      bone grafts and failure of instrumentation. A Charcot's arthropathy was formed
      between L4 and L5. CONCLUSION: It is challenging to diagnose the tertiary
      syphilis in the spine. Surgery is a reasonable auxiliary method to antibiotic
      therapy for patients who suffered with neuropathy. Charcot's arthropathy should
      be considered as an operative complication.

PMID- 28738853
TI  - Host gene-microbiome interactions: molecular mechanisms in inflammatory bowel
      disease.
AB  - Recent studies have identified links between host genetic variants and microbial
      recognition of the microbiome. Defects in host-microbiome interactions in
      individuals harboring inflammatory bowel disease risk alleles may result in
      imbalances of the microbial community, impaired pathogen clearance, and failure
      to sense beneficial commensal microbes. These findings highlight the importance
      of maintaining bi-directional communication at the mucosal interface during
      intestinal homeostasis.

PMID- 28738851
TI  - Expression and secretion of fungal endoglucanase II and chimeric
      cellobiohydrolase I in the oleaginous yeast Lipomyces starkeyi.
AB  - BACKGROUND: Lipomyces starkeyi is one of the leading lipid-producing
      microorganisms reported to date; its genetic transformation was only recently
      reported. Our aim is to engineer L. starkeyi to serve in consolidated
      bioprocessing (CBP) to produce lipid or fatty acid-related biofuels directly from
      abundant and low-cost lignocellulosic substrates. RESULTS: To evaluate L.
      starkeyi in this role, we first conducted a genome analysis, which revealed the
      absence of key endo- and exocellulases in this yeast, prompting us to select and
      screen four signal peptides for their suitability for the overexpression and
      secretion of cellulase genes. To compensate for the cellulase deficiency, we
      chose two prominent cellulases, Trichoderma reesei endoglucanase II (EG II) and a
      chimeric cellobiohydrolase I (TeTrCBH I) formed by fusion of the catalytic domain
      from Talaromyces emersonii CBH I with the linker peptide and cellulose-binding
      domain from T. reesei CBH I. The systematically tested signal peptides included
      three peptides from native L. starkeyi and one from Yarrowia lipolytica. We found
      that all four signal peptides permitted secretion of active EG II. We also
      determined that three of these signal peptides worked for expression of the
      chimeric CBH I; suggesting that our design criteria for selecting these signal
      peptides was effective. Encouragingly, the Y. lipolytica signal peptide was able
      to efficiently guide secretion of the chimeric TeTrCBH I protein from L.
      starkeyi. The purified chimeric TeTrCBH I showed high activity against the
      cellulose in pretreated corn stover and the purified EG II showed high
      endocellulase activity measured by the CELLG3 (Megazyme) method. CONCLUSIONS: Our
      results suggest that L. starkeyi is capable of expressing and secreting core
      fungal cellulases. Moreover, the purified EG II and chimeric TeTrCBH I displayed
      significant and potentially useful enzymatic activities, demonstrating that
      engineered L. starkeyi has the potential to function as an oleaginous CBP strain
      for biofuel production. The effectiveness of the tested secretion signals will
      also benefit future secretion of other heterologous proteins in L. starkeyi and,
      given the effectiveness of the cross-genus secretion signal, possibly other
      oleaginous yeasts as well.

PMID- 28738854
TI  - Understanding clinician attitudes towards implementation of guided self-help
      cognitive behaviour therapy for those who hear distressing voices: using factor
      analysis to test normalisation process theory.
AB  - BACKGROUND: The Normalisation Process Theory (NPT) has been used to understand
      the implementation of physical health care interventions. The current study aims
      to apply the NPT model to a secondary mental health context, and test the model
      using exploratory factor analysis. This study will consider the implementation of
      a brief cognitive behaviour therapy for psychosis (CBTp) intervention. METHODS:
      Mental health clinicians were asked to complete a NPT-based questionnaire on the
      implementation of a brief CBTp intervention. All clinicians had experience of
      either working with the target client group or were able to deliver psychological
      therapies. In total, 201 clinicians completed the questionnaire. RESULTS: The
      results of the exploratory factor analysis found partial support for the NPT
      model, as three of the NPT factors were extracted: (1) coherence, (2) cognitive
      participation, and (3) reflexive monitoring. We did not find support for the
      fourth NPT factor (collective action). All scales showed strong internal
      consistency. Secondary analysis of these factors showed clinicians to generally
      support the implementation of the brief CBTp intervention. CONCLUSIONS: This
      study provides strong evidence for the validity of the three NPT factors
      extracted. Further research is needed to determine whether participants' level of
      seniority moderates factor extraction, whether this factor structure can be
      generalised to other healthcare settings, and whether pre-implementation
      attitudes predict actual implementation outcomes.

PMID- 28738855
TI  - Approaches to health-care provider education and professional development in
      perinatal depression: a systematic review.
AB  - BACKGROUND: Perinatal depression is the most common mental illness experienced by
      pregnant and postpartum women, yet it is often under-detected and under-treated.
      Some researchers suggest this may be partly influenced by a lack of education and
      professional development on perinatal depression among health-care providers,
      which can negatively affect care and contribute to stigmatization of women
      experiencing altered mood. Therefore, the aim of this systematic review is to
      provide a synthesis of educational and professional development needs and
      strategies for health-care providers in perinatal depression. METHODS: A
      systematic search of the literature was conducted in seven academic health
      databases using selected keywords. The search was limited to primary studies and
      reviews published in English between January 2006 and May/June 2015, with a focus
      on perinatal depression education and professional development for health-care
      providers. Studies were screened for inclusion by two reviewers and tie-broken by
      a third. Studies that met inclusion criteria were quality appraised and data
      extracted. Results from the studies are reported through narrative synthesis.
      RESULTS: Two thousand one hundred five studies were returned from the search,
      with 1790 remaining after duplicate removal. Ultimately, 12 studies of moderate
      and weak quality met inclusion criteria. The studies encompassed quantitative (n
      = 11) and qualitative (n = 1) designs, none of which were reviews, and addressed
      educational needs identified by health-care providers (n = 5) and strategies for
      professional development in perinatal mental health (n = 7). Consistently,
      providers identified a lack of formal education in perinatal mental health and
      the need for further professional development. Although the professional
      development interventions were diverse, the majority focused on promoting
      identification of perinatal depression and demonstrated modest effectiveness in
      improving various outcomes. CONCLUSIONS: This systematic review reveals a lack of
      strong research in multi-disciplinary, sector, site, and modal approaches to
      education and professional development for providers to identify and care for
      women at risk for, or experiencing, depression. To ensure optimal health
      outcomes, further research comparing diverse educational and professional
      development approaches is needed to identify the most effective strategies and
      consistently meet the needs of health-care providers. TRIAL REGISTRATION: A
      protocol for this systematic review was registered on PROSPERO (Protocol number:
      CRD42015023701 ), June 21, 2015.

PMID- 28738856
TI  - Acute changes in blood lipid profiles and metabolic risk factors in collegiate
      elite taekwondo athletes after short-term de-training: a prospective insight for
      athletic health management.
AB  - BACKGROUND: This study used a short-term de-training model to mimic the
      physiological weight changes during the early retirement stage in Taekwondo (TKD)
      athletes. This study investigates whether the negative changes in body
      composition, blood lipid profiles, and metabolic biomarkers occur in elite
      collegiate TKD athletes when experiencing a two-months de-training period.
      METHODS: Fourteen collegiate Division Iota elite TKD athletes (age: 21.1 +/- 0.2
      years, BMI: 22.3 +/- 1.1 kg/m2; 10 males and 4 females) participated in this
      study. The body composition, blood lipid profiles, atherogenic dyslipidemia
      indexes, metabolic biomarkers and baseline systemic inflammation states were
      measured before and after two-months de-training. RESULTS: The body weight and
      BMI did not change after de-training in these elite TKD athletes. The total
      muscle mass displayed a significant decline after de-training (-2.0%, p = 0.019),
      with an increase in fat mass (+24.3%, p < 0.01). The blood triglyceride did not
      change, but the total cholesterol was higher after de-training (+8.3%, p =
      0.047). The CHOL-to-HDL and LDL-to-HDL ratios increased by 12.4% (p < 0.001) and
      13.2% (p = 0.002) after de-training, respectively. The blood platelet number,
      plateletcrit, and platelet-to-lymphocyte ratio increased significantly by 5.0% (p
      = 0.013), 7.3% (p = 0.009), and 20.6% (p = 0.018) after de-training,
      respectively. The McAuley's Index decreased (-6.9%, p = 0.025) after de-training.
      CONCLUSION: We demonstrated that a two-months de-training period resulted in
      adverse effects on early atherogenic dyslipidemia development, progressing
      insulin resistance, low-grade inflammation, and visceral adiposity in young elite
      TKD athletes. Our findings provide clear insights into the possible deleterious
      impacts at early stage retirement in former combative sports athletes.

PMID- 28738858
TI  - Erythema nodosum masking nephrogenic systemic fibrosis as initial skin
      manifestation.
AB  - BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a complication of the
      gadolinium-based contrast agent used in imaging studies. It is typically
      characterised by hard, erythematous and indurated skin plaques with surrounding
      subcutaneous oedema. Distinct papules and subcutaneous nodules can also be seen.
      Fibrocytes in NSF are immunohistochemically positive for CD34. CASE PRESENTATION:
      We present a case of NSF occurred after gadolinium exposure in which the initial
      presentation mimics an erythema nodosum (EN)-like picture. An initial skin biopsy
      showed EN. Subsequently the patient developed progressive skin and joints
      contracture. A repeated skin biopsy done three months later confirmed the
      diagnosis of NSF. As far as we are aware, this is the second reported case of NSF
      that mimicked the presentation of EN in the early phase of the disease.
      CONCLUSIONS: The appearance of EN-like disease can be one of the early
      manifestations of NSF. We hope that early recognition of this unusual
      presentation can alert the physician or nephrologist to the potential diagnosis
      of NSF.

PMID- 28738857
TI  - Investigating interventions to increase uptake of HIV testing and linkage into
      care or prevention for male partners of pregnant women in antenatal clinics in
      Blantyre, Malawi: study protocol for a cluster randomised trial.
AB  - BACKGROUND: Despite large-scale efforts to diagnose people living with HIV, 54%
      remain undiagnosed in sub-Saharan Africa. The gap in knowledge of HIV status and
      uptake of follow-on services remains wide with much lower rates of HIV testing
      among men compared to women. Here, we design a study to investigate the effect on
      uptake of HIV testing and linkage into care or prevention of partner-delivered
      HIV self-testing alone or with an additional intervention among male partners of
      pregnant women. METHODS: A phase II, adaptive, multi-arm, multi-stage cluster
      randomised trial, randomising antenatal clinic (ANC) days to six different trial
      arms. Pregnant women accessing ANC in urban Malawi for the first time will be
      recruited into either the standard of care (SOC) arm (invitation letter to the
      male partner offering HIV testing) or one of five intervention arms offering oral
      HIV self-test kits. Three of the five intervention arms will additionally offer
      the male partner a financial incentive (fixed or lottery amount) conditional on
      linkage after self-testing with one arm testing phone call reminders. Assuming
      that 25% of male partners link to care or prevention in the SOC arm, six clinic
      days, with a harmonic mean of 21 eligible participants, per arm will provide 80%
      power to detect a 0.15 absolute difference in the primary outcome. Cluster
      proportions will be analysed by a cluster summaries approach with adjustment for
      clustering and multiplicity. DISCUSSION: This trial applies adaptive methods
      which are novel and efficient designs. The methodology and lessons learned here
      will be important as proof of concept of how to design and conduct similar
      studies in the future. Although small, this trial will potentially present good
      evidence on the type of effective interventions for improving linkage into ART or
      prevention. The trial results will also have important policy implications on how
      to implement HIVST targeting male partners of pregnant women who are accessing
      ANC for the first time while paying particular attention to safety concerns.
      Contamination may occur if women in the intervention arms share their self-test
      kits with women in the SOC arm. TRIAL REGISTRATION: ISRCTN, ID: 18421340 .
      Registered on 31 March 2016.

PMID- 28738859
TI  - Genes and pathways underlying susceptibility to impaired lung function in the
      context of environmental tobacco smoke exposure.
AB  - BACKGROUND: Studies aiming to assess genetic susceptibility for impaired lung
      function levels upon exposure to environmental tobacco smoke (ETS) have thus far
      focused on candidate-genes selected based on a-priori knowledge of potentially
      relevant biological pathways, such as glutathione S-transferases and ADAM33. By
      using a hypothesis-free approach, we aimed to identify novel susceptibility loci,
      and additionally explored biological pathways potentially underlying this
      susceptibility to impaired lung function in the context of ETS exposure. METHODS:
      Genome-wide interactions of single nucleotide polymorphism (SNP) by ETS exposure
      (0 versus >=1 h/day) in relation to the level of forced expiratory volume in one
      second (FEV1) were investigated in 10,817 subjects from the Dutch LifeLines
      cohort study, and verified in subjects from the Swiss SAPALDIA study (n = 1276)
      and the Dutch Rotterdam Study (n = 1156). SNP-by-ETS exposure p-values obtained
      from the identification analysis were used to perform a pathway analysis.
      RESULTS: Fourty Five SNP-by-ETS exposure interactions with p-values <10-4 were
      identified in the LifeLines study, two being replicated with nominally
      significant p-values (<0.05) in at least one of the replication cohorts. Three
      pathways were enriched in the pathway-level analysis performed in the
      identification cohort LifeLines, i.E. the apoptosis, p38 MAPK and TNF pathways.
      CONCLUSION: This unique, first genome-wide gene-by-ETS interaction study on the
      level of FEV1 showed that pathways previously implicated in chronic obstructive
      pulmonary disease (COPD), a disease characterized by airflow obstruction, may
      also underlie susceptibility to impaired lung function in the context of ETS
      exposure.

PMID- 28738860
TI  - Germline EMSY sequence alterations in hereditary breast cancer and ovarian cancer
      families.
AB  - BACKGROUND: BRCA1 and BRCA2 mutations explain approximately one-fifth of the
      inherited susceptibility in high-risk Finnish hereditary breast and ovarian
      cancer (HBOC) families. EMSY is located in the breast cancer-associated
      chromosomal region 11q13. The EMSY gene encodes a BRCA2-interacting protein that
      has been implicated in DNA damage repair and genomic instability. We analysed the
      role of germline EMSY variation in breast/ovarian cancer predisposition. The
      present study describes the first EMSY screening in patients with high familial
      risk for this disease. METHODS: Index individuals from 71 high-risk, BRCA1/2
      negative HBOC families were screened for germline EMSY sequence alterations in
      protein coding regions and exon-intron boundaries using Sanger sequencing and
      TaqMan assays. The identified variants were further screened in 36 Finnish HBOC
      patients and 904 controls. Moreover, one novel intronic deletion was screened in
      a cohort of 404 breast cancer patients unselected for family history. Haplotype
      block structure and the association of haplotypes with breast/ovarian cancer were
      analysed using Haploview. The functionality of the identified variants was
      predicted using Haploreg, RegulomeDB, Human Splicing Finder, and Pathogenic-or
      Not-Pipeline 2. RESULTS: Altogether, 12 germline EMSY variants were observed. Two
      alterations were located in the coding region, five alterations were intronic,
      and five alterations were located in the 3'untranslated region (UTR). Variant
      frequencies did not significantly differ between cases and controls. The novel
      variant, c.2709 + 122delT, was detected in 1 out of 107 (0.9%) breast cancer
      patients, and the carrier showed a bilateral form of the disease. The deletion
      was absent in 897 controls (OR = 25.28; P = 0.1) and in 404 breast cancer
      patients unselected for family history. No haplotype was identified to increase
      the risk of breast/ovarian cancer. Functional analyses suggested that variants,
      particularly in the 3'UTR, were located within regulatory elements. The novel
      deletion was predicted to affect splicing regulatory elements. CONCLUSIONS: These
      results suggest that the identified EMSY variants are likely neutral at the
      population level. However, these variants may contribute to breast/ovarian cancer
      risk in single families. Additional analyses are warranted for rare novel
      intronic deletions and the 3'UTR variants predicted to have functional roles.

PMID- 28738861
TI  - The risk of HIV transmission at each step of the HIV care continuum among people
      who inject drugs: a modeling study.
AB  - BACKGROUND: People who inject drugs (PWID) are at continued risk for HIV in the
      U.S., and experience disparities across the HIV care continuum compared to other
      high-risk groups. Estimates of the risk of HIV transmission at each stage of the
      care continuum may assist in identifying public health priorities for averting
      incident infections among PWID, in addition to transmissions to sexual partners
      of PWID. METHODS: We created an agent-based model simulating HIV transmission and
      the HIV care continuum for PWID in New York City (NYC) in 2012. To account for
      sexual transmission arising from PWID to non-PWID, the simulation included the
      entire adult NYC population. Using surveillance data and estimates from the
      National HIV Behavioral Surveillance system, we simulated a dynamic sexual and
      injecting network. We estimated the proportion of HIV transmission events
      attributable to PWID in the following categories, those: without an HIV diagnosis
      ('Undiagnosed'); diagnosed but not on antiretroviral therapy (ART) ('Diagnosed -
      not on ART'); those who initiated ART but were not virally suppressed
      ('Unsuppressed'); and, those who achieved viral suppression ('Suppressed').
      RESULTS: We estimated HIV incidence among PWID to be 113 per 100,000 person-years
      in 2012, with an overall incidence rate for the entire adult NYC population of 33
      per 100,000 person-years. Despite accounting for only 33% of the HIV-infected
      PWID population, the Undiagnosed were associated with 52.6% (95% simulation
      interval [95% SI]: 47.1-57.0%) of total transmission events. The Diagnosed - not
      on ART population contributed the second-largest proportion of HIV transmissions,
      with 36.6% (95% SI: 32.2-41.5%). The Unsuppressed population contributed 8.7%
      (95% SI: 5.6-11.8%), and Suppressed 2.1% (95% SI: 1.1-3.9%), relatively little of
      overall transmission. CONCLUSIONS: Among PWID in NYC, more than half (53%) of
      transmissions were from those who were unaware of their infection status and more
      than 36% were due to PWID who knew their status, but were not on treatment. Our
      results indicate the importance of early diagnosis and interventions to engage
      diagnosed PWID on treatment to further suppress population-level HIV
      transmission. Future HIV prevention research should focus on the elimination of
      identified and potential barriers to the testing, diagnosis, and retention of
      PWID on HIV treatment.

PMID- 28738862
TI  - Impact of ischemic preconditioning on surgical treatment of brain tumors: a
      single-center, randomized, double-blind, controlled trial.
AB  - BACKGROUND: Postoperative ischemia is a frequent phenomenon in patients with
      brain tumors and is associated with postoperative neurological deficits and
      impaired overall survival. Particularly in the field of cardiac and vascular
      surgery, the application of a brief ischemic stimulus not only in the target
      organ but also in remote tissues can prevent subsequent ischemic damage. We
      hypothesized that remote ischemic preconditioning (rIPC) in patients with brain
      tumors undergoing elective surgical resection reduces the incidence of
      postoperative ischemic tissue damage and its consequences. METHODS: Sixty
      patients were randomly assigned to two groups, with 1:1 allocation, stratified by
      tumor type (glioma or metastasis) and previous treatment with radiotherapy. rIPC
      was induced by inflating a blood pressure cuff placed on the upper arm three
      times for 5 min at 200 mmHg in the treatment group after induction of anesthesia.
      Between the cycles, the blood pressure cuff was released to allow reperfusion. In
      the control group no preconditioning was performed. Early postoperative magnetic
      resonance images (within 72 h after surgery) were evaluated by a neuroradiologist
      blinded to randomization for the presence of ischemia and its volume. RESULTS:
      Fifty-eight of the 60 patients were assessed for occurrence of postoperative
      ischemia. Of these 58 patients, 44 had new postoperative ischemic lesions. The
      incidence of new postoperative ischemic lesions was significantly higher in the
      control group (27/31) than in the rIPC group (17/27) (p = 0.03). The median
      infarct volume was 0.36 cm3 (interquartile range (IR): 0.0-2.35) in the rIPC
      group compared with 1.30 cm3 (IR: 0.29-3.66) in the control group (p = 0.09).
      CONCLUSIONS: Application of rIPC was associated with reduced incidence of
      postoperative ischemic tissue damage in patients undergoing elective brain tumor
      surgery. This is the first study indicating a benefit of rIPC in brain tumor
      surgery. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00010409 .
      Retrospectively registered on 13 October 2016.

PMID- 28738863
TI  - Single coronary ostium in a patient with quadricuspid aortic valve combined with
      aneurysmal ascending aortic dilatation.
AB  - BACKGROUND: The presence of a fourth aortic valve cusp (quadricupsid aortic
      valve) is a rare congenital malformation and is often accompanied by other
      anomalies of the adjacent cardiovascular structures. Among these concomitant
      anomalies, simultaneous association of both a single coronary ostium and
      aneurysmal ascending aortic dilation in combination with the quadricupsid aortic
      valve has not been reported yet. CASE PRESENTATION: We experienced the case of a
      56-year-old female patient presenting as aortic regurgitation resulted from
      malcoaptation of quadricupsid aortic valve. The patient had also accompanying
      aneurysmal ascending aortic dilatation and coronary ostial anomaly. Surgical
      correction (aortic valve replacement with mechanical devices and supracoronary
      aortic replacement with prosthetic graft) was performed without any
      complications. CONCLUSIONS: The technological development of preoperative imaging
      studies enable the physician to encounter the quadricuspid aortic valve with
      other associated malformations more often unlike previous reports. With review on
      the quadricuspid aortic valve, we discussed a surgical considerations for the
      treatment of this anomaly.

PMID- 28738864
TI  - Identification of two organohalide-respiring Dehalococcoidia associated to
      different dechlorination activities in PCB-impacted marine sediments.
AB  - BACKGROUND: Microbial reductive dechlorination of polychlorinated biphenyls
      (PCBs) plays a major role in detoxifying anoxic contaminated freshwater and
      marine sediments from PCBs. Known members of the phylum Chloroflexi are typically
      responsible for this activity in freshwater sediments, whereas less is known
      about the microorganisms responsible for this activity in marine sediments. PCB
      respiring activities were detected in PCB-impacted marine sediments of the Venice
      Lagoon. The aim of this work was to identify the indigenous organohalide
      respiring microorganisms in such environments and assess their dechlorination
      specificity against spiked AroclorTM 1254 PCBs under laboratory conditions
      resembling the in situ biogeochemistry. RESULTS: High PCB dechlorination
      activities (from 150 +/- 7 to 380 +/- 44 MUmol of chlorine removed kg-1 week-1)
      were detected in three out of six sediments sampled from different locations of
      the lagoon. An uncultured non-Dehalococcoides phylotype of the class
      Dehalococcoidia closely related to Dehalobium chlorocoercia DF-1, namely
      phylotype VLD-1, was detected and enriched up to 109 16S rRNA gene copies per
      gram of sediment where dechlorination activities were higher and 25-4/24-4 and 25
      2/24-2/4-4 chlorobiphenyls (CB) accumulated as the main tri-/dichlorinated
      products. Conversely, a different phylotype closely related to the SF1/m-1 clade,
      namely VLD-2, also enriched highly where lower dechlorination activity and the
      accumulation of 25-3 CB as main tri-chlorinated product occurred, albeit in the
      simultaneous presence of VLD-1. Both phylotypes showed growth yields higher or
      comparable to known organohalide respirers and neither phylotypes enriched in
      sediment cultures not exhibiting dechlorination. CONCLUSIONS: These findings
      confirm the presence of different PCB-respiring microorganisms in the indigenous
      microbial communities of Venice Lagoon sediments and relate two non
      Dehalococcoides phylotypes of the class Dehalococcoidia to different PCB
      dechlorination rates and specificities.

PMID- 28738865
TI  - Avian influenza H9N2 virus isolated from air samples in LPMs in Jiangxi, China.
AB  - BACKGROUND: Recently, avian influenza virus has caused repeated worldwide
      outbreaks in humans. Live Poultry Markets (LPMs) play an important role in the
      circulation and reassortment of novel Avian Influenza Virus (AIVs). Aerosol
      transmission is one of the most important pathways for influenza virus to spread
      among poultry, from poultry to mammals, and among mammals. METHODS: In this
      study, air samples were collected from LPMs in Nanchang city between April 2014
      and March 2015 to investigate possible aerosol transmission of AIVs. Air samples
      were detected for Flu A by Real-Time Reverse Transcription-Polymerase Chain
      Reaction (RRT-PCR). If samples were positive for Flu A, they were inoculated into
      9- to 10-day-old specific-pathogen-free embryonated eggs. If the result was
      positive, the whole genome of the virus was sequenced by MiSeq. Phylogenetic
      trees of all 8 segments were constructed using MEGA 6.05 software. RESULTS: To
      investigate the possible aerosol transmission of AIVs, 807 air samples were
      collected from LPMs in Nanchang city between April 2014 and March 2015. Based on
      RRT-PCR results, 275 samples (34.1%) were Flu A positive, and one virus was
      successfully isolated with embryonated eggs. The virus shared high nucleotide
      homology with H9N2 AIVs from South China. CONCLUSIONS: Our study provides further
      evidence that the air in LPMs can be contaminated by influenza viruses and their
      nucleic acids, and this should be considered when choosing and evaluating
      disinfection strategies in LPMs, such as regular air disinfection. Aerosolized
      viruses such as the H9N2 virus detected in this study can increase the risk of
      human infection when people are exposed in LPMs.

PMID- 28738866
TI  - Frequency, associated features, and burden of neurological disorders in older
      adult inpatients in Brazil: a retrospective cross-sectional study.
AB  - BACKGROUND: The burden of neurological disorders (NDs) in older adult inpatients
      is often underestimated. We studied diagnostic frequency and comorbidity of NDs
      among inpatients aged >=60 years. We compared rates of hospital mortality, length
      of stay (LOS), and readmission with younger patient counterparts (aged 18-59
      years) and older adult non-neurological patients. METHODS: This was a
      retrospective cross-sectional study of inpatients in a tertiary care center in
      Brazil. We compiled data for all patients admitted between 1 January 2009 and 31
      December 2010, and selected those aged >=18 years for inclusion in the study. We
      collected data for inpatients under care of a clinical neurologist who were
      discharged with primary diagnoses of NDs or underlying acute clinical disorders,
      and data for complications in clinical or surgical inpatients. Patients who
      remained hospitalized for more than 9 days were categorized as having long LOS.
      RESULTS: Older adult inpatients with NDs (n = 798) represented 56% of all
      neurological inpatients aged >=18 years (n = 1430), and 14% of all geriatric
      inpatients (n = 5587). The mean age of older adult inpatients was 75 +/- 9.1
      years. Women represented 55% of participants. The most common NDs were
      cerebrovascular diseases (51%), although multimorbidity was observed. Hospital
      mortality rate was 18% (95% confidence interval [CI], 15-21) and readmission rate
      was 31% (95% CI, 28-35), with 40% of patients readmitted 1.8 +/- 1.5 times. The
      long LOS rate was 51% and the median LOS was 9 days (interquartile interval, 1-20
      days). In younger inpatients mortality rate was 1.4%, readmission rate was 34%,
      and long LOS rate was 14%. In older adult non-neurological inpatients, mortality
      rate was 22%, readmission rate was 49%, and long LOS rate was 30%. CONCLUSIONS:
      Older adult neurological inpatients had the highest long LOS rate of all patient
      groups, and a higher mortality rate than neurological patients aged 18-59 years.
      Readmissions were high in all groups studied, particularly among older adult non
      neurological inpatients. Improved structures and concerted efforts are required
      in hospitals in Brazil to reduce burden of NDs in older adult patients.

PMID- 28738867
TI  - Q&A: What is human language, when did it evolve and why should we care?
AB  - Human language is unique among all forms of animal communication. It is unlikely
      that any other species, including our close genetic cousins the Neanderthals,
      ever had language, and so-called sign 'language' in Great Apes is nothing like
      human language. Language evolution shares many features with biological
      evolution, and this has made it useful for tracing recent human history and for
      studying how culture evolves among groups of people with related languages. A
      case can be made that language has played a more important role in our species'
      recent (circa last 200,000 years) evolution than have our genes.

PMID- 28738868
TI  - Comparative evaluation of fluorescent in situ hybridization and Giemsa microscopy
      with quantitative real-time PCR technique in detecting malaria parasites in a
      holoendemic region of Kenya.
AB  - BACKGROUND: Early and accurate diagnosis of malaria is important in treatment as
      well as in the clinical evaluation of drugs and vaccines. Evaluation of Giemsa
      stained smears remains the gold standard for malaria diagnosis, although
      diagnostic errors and potential bias estimates of protective efficacy have been
      reported in practice. Plasmodium genus fluorescent in situ hybridization (P-Genus
      FISH) is a microscopy-based method that uses fluorescent labelled oligonucleotide
      probes targeted to pathogen specific ribosomal RNA fragments to detect malaria
      parasites in whole blood. This study sought to evaluate the diagnostic
      performance of P-Genus FISH alongside Giemsa microscopy compared to quantitative
      reverse transcription polymerase chain reaction (qRT-PCR) in a clinical setting.
      METHOD: Five hundred study participants were recruited prospectively and screened
      for Plasmodium parasites by P-Genus FISH assay, and Giemsa microscopy. The
      microscopic methods were performed by two trained personnel and were blinded, and
      if the results were discordant a third reading was performed as a tie breaker.
      The diagnostic performance of both methods was evaluated against qRT-PCR as a
      more sensitive method. RESULTS: The number of Plasmodium positive cases was 26.8%
      by P-Genus FISH, 33.2% by Giemsa microscopy, and 51.2% by qRT-PCR. The three
      methods had 46.8% concordant results with 61 positive cases and 173 negative
      cases. Compared to qRT-PCR the sensitivity and specificity of P-Genus FISH assay
      was 29.3 and 75.8%, respectively, while microscopy had 58.2 and 93.0%
      respectively. Microscopy had a higher positive and negative predictive values
      (89.8 and 68.0% respectively) compared to P-Genus FISH (56.0 and 50.5%). In
      overall, microscopy had a good measure of agreement (76%, k = 0.51) compared to P
      Genus FISH (52%, k = 0.05). CONCLUSION: The diagnostic performance of P-Genus
      FISH was shown to be inferior to Giemsa microscopy in the clinical samples. This
      hinders the possible application of the method in the field despite the many
      advantages of the method especially diagnosis of low parasite density infections.
      The P-Genus assay has great potential but application of the method in clinical
      setting would rely on extensive training of microscopist and continuous
      proficiency testing.

PMID- 28738869
TI  - Maternal depression in Syrian refugee women recently moved to Canada: a
      preliminary study.
AB  - BACKGROUND: Refugee women are almost five times more likely to develop postpartum
      depression than Canadian-born women. This can be attributed to various
      difficulties they faced before coming to Canada as well as during resettlement.
      Moreover, refugee women usually face many obstacles when accessing health
      services, including language and cultural barriers, as well as unique help
      seeking behaviors that are influenced by various cultural and practical factors.
      There has been a recent, rapid influx of Syrian refugees to Canada, and many of
      them are childbearing women. However, little is known about the experiences that
      these women have encountered pre- and post-resettlement, and their perceptions of
      mental health issues. Thus, there is an urgent need to understand refugee women's
      experiences of having a baby in Canada from a mental health perspective. METHODS:
      A mixed methods research design included 12 Syrian refugee women who migrated to
      Saskatoon in 2015-16 and who were either pregnant or 1 year postpartum. The data
      were collected during a single focus group discussion and a structured
      questionnaire. RESULTS: Our results showed that more than half of participants
      have depressive symptoms, half of them have anxiety symptoms, and one sixth have
      PTSD symptoms. Three major themes emerged from the qualitative data: 1)
      Understanding of maternal depression; 2) Protective factors for mental health;
      and 3) Barriers to mental health services. CONCLUSIONS: Maternal depression is an
      important feature in Syrian refugee women recently resettled in Canada. Reuniting
      these women with their families and engaging them in culturally appropriate
      support programs may improve their mental health outcomes.

PMID- 28738870
TI  - Cross-sectional description of nursing and midwifery pre-service education
      accreditation in east, central, and southern Africa in 2013.
AB  - BACKGROUND: In 2013, the World Health Organization issued guidelines,
      Transforming and Scaling Up Health Professional Education and Training, to
      improve the quality and relevance of health professional pre-service education.
      Central to these guidelines was establishing and strengthening education
      accreditation systems. To establish what current accreditation systems were for
      nursing and midwifery education and highlight areas for strengthening these
      systems, a study was undertaken to document the pre-service accreditation
      policies, approaches, and practices in 16 African countries relative to the 2013
      WHO guidelines. METHODS: This study utilized a cross-sectional group survey with
      a standardized questionnaire administered to a convenience sample of
      approximately 70 nursing and midwifery leaders from 16 countries in east,
      central, and southern Africa. Each national delegation completed one survey
      together, representing the responses for their country. RESULTS: Almost all
      countries in this study (15; 94%) mandated pre-service nursing education
      accreditation However, there was wide variation in who was responsible for
      accrediting programs. The percent of active programs accredited decreased by
      program level from 80% for doctorate programs to 62% for masters nursing to 50%
      for degree nursing to 35% for diploma nursing programs. The majority of countries
      indicated that accreditation processes were transparent (i.e., included
      stakeholder engagement (81%), self-assessment (100%), evaluation feedback (94%),
      and public disclosure (63%)) and that the processes were evaluated on a routine
      basis (69%). Over half of the countries (nine; 56%) reported limited financial
      resources as a barrier to increasing accreditation activities, and seven
      countries (44%) noted limited materials and technical expertise. CONCLUSION: In
      line with the 2013 WHO guidelines, there was a strong legal mandate for nursing
      education accreditation as compared to the global average of 50%. Accreditation
      levels were low in the programs that produce the majority of the nurses in this
      region and were higher in public programs than non-public programs. WHO
      guidelines for transparency and routine review were met more so than standards
      based and independent accreditation processes. The new global strategy, Workforce
      2030, has renewed the focus on accreditation and provides an opportunity to
      strengthen pre-service accreditation and ensure the production of a qualified and
      relevant nursing workforce.

PMID- 28738871
TI  - Highly suspected cases of salmonellosis in two cats fed with a commercial raw
      meat-based diet: health risks to animals and zoonotic implications.
AB  - BACKGROUND: Feeding raw meat-based diets (RMBD) to companion animals raises
      public health concerns for both animals and humans. While considerable attention
      has been paid to bacterial contamination of commercial pet food, few literature
      studies have investigated foodborne disease in companion animals. Salmonellosis
      is reported to be infrequent in cats but no known data or studies estimating
      feline salmonellosis are available or large-scale epidemiological studies
      assessing Salmonella risk factors. CASE PRESENTATION: Two highly suspected cases
      of salmonellosis in two cats fed with a commercial frozen poultry RMBD are
      presented, for the first time from the same household. The clinical presentation,
      diagnostics, treatment and follow-up are reported and the zoonotic implications
      are discussed. CONCLUSIONS: This case highlights the health risks posed to both
      animals and owners by feeding RMBD to pets, and suggests that these risks should
      be considered by veterinary practitioners.

PMID- 28738872
TI  - A population-based study of homicide deaths in Ontario, Canada using linked death
      records.
AB  - BACKGROUND: Homicide - a lethal expression of violence - has garnered little
      attention from public health researchers and health policy makers, despite the
      fact that homicides are a cause of preventable and premature death. Identifying
      populations at risk and the upstream determinants of homicide are important for
      addressing inequalities that hinder population health. This population-based
      study investigates the public health significance of homicides in Ontario,
      Canada, over the period of 1999-2012. We quantified the relative burden of
      homicides by comparing the socioeconomic gradient in homicides with the leading
      causes of death, cardiovascular disease (CVD) and neoplasm, and estimated the
      potential years of life lost (PYLL) due to homicide. METHODS: We linked vital
      statistics from the Office of the Registrar General Deaths register (ORG-D) with
      Census and administrative data for all Ontario residents. We extracted all
      homicide, neoplasm, and cardiovascular deaths from 1999 to 2012, using
      International Classification of Diseases codes. For socioeconomic status (SES),
      we used two dimensions of the Ontario Marginalization Index (ON-Marg): material
      deprivation and residential instability. Trends were summarized across
      deprivation indices using age-specific rates, rate ratios, and PYLL. RESULTS:
      Young males, 15-29 years old, were the main victims of homicide with a rate of
      3.85 [IC 95%: 3.56; 4.13] per 100,000 population and experienced an upward trend
      over the study period. The socioeconomic neighbourhood gradient was substantial
      and higher than the gradient for both cardiovascular and neoplasms. Finally, the
      PYLL due to homicide were 63,512 and 24,066 years for males and females,
      respectively. CONCLUSIONS: Homicides are an important cause of death among young
      males, and populations living in disadvantaged neighbourhoods. Our findings raise
      concerns about the burden of homicides in the Canadian population and the
      importance of addressing social determinants to address these premature deaths.

PMID- 28738873
TI  - MATCHER: manifold alignment reveals correspondence between single cell
      transcriptome and epigenome dynamics.
AB  - Single cell experimental techniques reveal transcriptomic and epigenetic
      heterogeneity among cells, but how these are related is unclear. We present
      MATCHER, an approach for integrating multiple types of single cell measurements.
      MATCHER uses manifold alignment to infer single cell multi-omic profiles from
      transcriptomic and epigenetic measurements performed on different cells of the
      same type. Using scM&T-seq and sc-GEM data, we confirm that MATCHER accurately
      predicts true single cell correlations between DNA methylation and gene
      expression without using known cell correspondences. MATCHER also reveals new
      insights into the dynamic interplay between the transcriptome and epigenome in
      single embryonic stem cells and induced pluripotent stem cells.

PMID- 28738874
TI  - How do national contraception laws and policies address the contraceptive needs
      of adolescents in Paraguay?
AB  - BACKGROUND: The main objective is to examine how the Paraguayan laws, policies
      and regulations (hereafter referred to as normative guidance) specifically
      address adolescents and their contraceptive information and service needs using a
      human rights analytic framework. It must be noted that this paper examines the
      adolescent content of national laws, policies and regulations on contraception,
      not how they were applied. METHODS: The recommendations on "Ensuring human rights
      in the provision of contraceptive information and services" from the World Health
      Organization (WHO) were used as an analytic framework to assess current
      Paraguayan laws, policies and regulations. Three questions were explored: 1)
      whether the Paraguayan normative guidance relating to each WHO recommendation was
      present and specifically addressed adolescents 2) whether the normative guidance
      for each WHO recommendation was present but did not specifically address
      adolescents, or 3) whether Paraguayan normative guidance relating to each WHO
      recommendation was absent. This assessment led to the development of an analytic
      table which was used by the co-authors to generate conclusions and
      recommendations. RESULTS: The analysis found specific normative guidance for
      adolescents relating to six out of nine WHO summary recommendations and nine out
      of the 24 sub-recommendations. The guidance included strategies to overcome
      contraceptive service barriers and to improve access for displaced populations.
      Further, it supported gender-sensitive counselling, quality assurance processes,
      competency-based training, and monitoring and evaluation of programmes.
      CONCLUSIONS: Paraguay's contraception laws and policies are grounded in human
      rights principles. However, there are a number of aspects that need to be
      addressed in order to improve the quality of contraceptive provision and access
      for adolescents. Our recommendations include improving accessibility of
      contraceptive information and services, ensuring acceptability, quality, and
      accountability of contraceptive information and services, and promoting community
      and adolescent participation in contraceptive programmes and service delivery.

PMID- 28738875
TI  - Effects of FTY720 on brain neurogenic niches in vitro and after kainic acid
      induced injury.
AB  - BACKGROUND: FTY720 (fingolimod, GilenyaTM) is an oral, blood-brain barrier (BBB)
      passing drug approved as immunomodulatory treatment for relapsing-remitting form
      of the multiple sclerosis (MS). In addition, FTY720 exerts several effects in the
      central nervous system (CNS), ranging from neuroprotection to reduction of
      neuroinflammation. However, the neurogenic and oligodendrogenic potential of
      FTY720 has been poorly investigated. In this study, we assessed the effect of
      FTY720 on the production of new neurons and oligodendrocytes from neural
      stem/precursor cells both in vitro and in vivo. METHODS: Neural stem cells (NSCs)
      derived from the young rat subventricular zone (SVZ) were exposed to FTY720 (10,
      100 nM), and their differentiation into neurons and oligodendrocytes was measured
      using immunofluorescence for anti-beta-III tubulin or CNPase (2',3'-cyclic
      nucleotide 3'-phosphodiesterase) as markers of mature neurons or
      oligodendrocytes, respectively. In addition, intracerebroventricular (icv)
      administration of kainic acid (KA; 0.5 MUg/2 MUl) in Sprague-Dawley rats was used
      as an in vivo model of neuronal death and inflammation. FTY720 was applied icv (1
      MUg/2 MUl), together with KA, plus intraperitoneally (ip; 1 mg/kg) 24 h before,
      and daily, until sacrifice 8 days after KA injection. To visualize cell
      proliferation in the hippocampus and in white matter regions, rats were
      administered 5-bromo-2-deoxyuridine (BrdU) 100 mg/kg, ip injected every 2 days.
      Immunohistochemical analyses were performed on rat brain slices to measure the
      production of new neuronal precursors (doublecortin/DCX+ cells) and new
      oligodendrocytes precursors (proteoglycan/NG2+ cells). RESULTS: In this study, we
      observed that FTY720 increased postnatal NSCs differentiation into both neurons
      and oligodendrocytes in vitro. In turn, in adult animals, FTY720 enhanced the
      percentage of BrdU+ cells coexpressing DCX marker, both in basal (FTY720 alone)
      and in neurodegenerative (FTY720 + KA) conditions. However, FTY720 had only a
      partial effect on proliferation and differentiation of oligodendrocyte progenitor
      cell (OPC) population in vivo. CONCLUSIONS: FTY720 promotes neurogenesis and
      oligodendrogenesis in vitro under basal conditions. In addition, it increases the
      generation of neuroblasts and oligodendrocytes after excitotoxic brain injury.
      This suggests that FTY720 has the potential to activate the neurogenic niche and
      thus favour tissue repair after lesion.

PMID- 28738876
TI  - Enterolactone has stronger effects than enterodiol on ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is one of the three leading gynecological
      malignancies, characterized by insidious growth, highly frequent metastasis, and
      quick development of drug resistance. As a result, this disease has low 5-year
      survival rates. Estrogen receptor inhibitors were commonly used for the
      treatment, but only 7% to 18% of patients respond to anti-estrogen therapies.
      Therefore, more effective therapies to inhibit estrogen-related tumors are
      urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like
      biological activities, have attracted attention for their potential effects in
      the prevention or treatment of estrogen-related diseases. Enterodiol (END) and
      enterolactone (ENL) are mammalian lignans, which can reduce the risk of various
      cancers. However, the effects of END and ENL on ovarian cancer are not adequately
      documented. METHODS: We used in vitro assays on the ES-2 cell line to evaluate
      the inhibiting effects of END and ENL on ovarian cancer cell proliferation,
      invasion and migration ability and in vivo xenograft experiments on nude mice to
      validate the anticancer effects of END and ENL. RESULTS: The in vitro assays
      demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant
      properties, including cancerous proliferation, invasion, and metastasis. Compared
      to END, ENL behaved in a better time-dose dependent manner on the cancer cells.
      The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1
      mg/kg) suppressed tumor markedly, and there were statistically significant
      differences between the experimental and control groups in tumor weight and
      volume. Compared to END, which have serious side effects to the animals at high
      concentration such as 1 mg/kg, ENL had higher anticancer activities and less side
      effects in the animals than END at the same concentrations, so it would be a
      better candidate for drug development. CONCLUSION: END and ENL both have potent
      inhibitory effects on ovarian cancer but ENL possesses a more effective anti
      cancer capability and less side effects than END. Findings in this work provide
      novel insights into ovarian cancer therapeutics with phytoestrogens and encourage
      their clinical applications.

PMID- 28738877
TI  - Unexpected complexity in the interference activity of a cloned influenza
      defective interfering RNA.
AB  - BACKGROUND: Defective interfering (DI) viruses are natural antivirals made by
      nearly all viruses. They have a highly deleted genome (thus being non-infectious)
      and interfere with the replication of genetically related infectious viruses. We
      have produced the first potential therapeutic DI virus for the clinic by cloning
      an influenza A DI RNA (1/244) which was derived naturally from genome segment 1.
      This is highly effective in vivo, and has unexpectedly broad-spectrum activity
      with two different modes of action: inhibiting influenza A viruses through RNA
      interference, and all other (interferon-sensitive) respiratory viruses through
      stimulating interferon type I. RESULTS: We have investigated the RNA inhibitory
      mechanism(s) of DI 1/244 RNA. Ablation of initiation codons does not diminish
      interference showing that no protein product is required for protection. Further
      analysis indicated that 1/244 DI RNA interferes by replacing the cognate full
      length segment 1 RNA in progeny virions, while interfering with the expression of
      genome segment 1, its cognate RNA, and genome RNAs 2 and 3, but not genome RNA 6,
      a representative of the non-polymerase genes. CONCLUSIONS: Our data contradict
      the dogma that a DI RNA only interferes with expression from its cognate full
      length segment. There is reciprocity as cloned segment 2 and 3 DI RNAs inhibited
      expression of RNAs from a segment 1 target. These data demonstrate an unexpected
      complexity in the mechanism of interference by this cloned therapeutic DI RNA.

PMID- 28738879
TI  - Do we publish what we preach? Analysis of the European Society for Surgery of the
      Shoulder and Elbow Congress publication rates.
AB  - BACKGROUND: Scientific congresses have become the most expedient method to
      communicate novel findings on any research topic. However, an important question
      is whether this information will be published in peer-reviewed journals. Our aim
      was to determine the publication rate of the abstracts presented at the European
      Society for Surgery of the Shoulder and Elbow Congress and analyze factors that
      may influence this rate. METHODS: A total of 398 abstracts reported in the
      Abstract Book from the 2008 European Society for Surgery of the Shoulder and
      Elbow Congress were examined and categorized by oral and poster presentations,
      topic, and the number of authors listed. A search in PubMed and Google Scholar
      for subsequent peer-reviewed publications was performed in September 2015. The
      time to publication after the meeting had been held; the type of journal and its
      impact factor at the time to publication were recorded for those abstracts that
      reached peer-reviewed journal publication. RESULTS: The overall publication rate
      for the 2008 European Society for Surgery of the Shoulder and Elbow oral and
      poster presentations was 45.20% after 7 years. The mean time to publication was
      18.53 months, and the mean impact factor value was 2.32. Oral presentations were
      significantly better represented in journals than posters (64.40 vs. 35.40%, p <
      0.001). Abstracts with a greater number of authors listed had better publication
      rates (p < 0.001). CONCLUSION: Less than half of the oral presentations and
      posters at the 21st European Society for Surgery of the Shoulder and Elbow
      Congress were published in peer-reviewed journals. Oral presentations with a
      higher number of authors had an increased likelihood of being published.

PMID- 28738878
TI  - TLR4 response mediates ethanol-induced neurodevelopment alterations in a model of
      fetal alcohol spectrum disorders.
AB  - BACKGROUND: Inflammation during brain development participates in the
      pathogenesis of early brain injury and cognitive dysfunctions. Prenatal ethanol
      exposure affects the developing brain and causes neural impairment, cognitive and
      behavioral effects, collectively known as fetal alcohol spectrum disorders
      (FASD). Our previous studies demonstrate that ethanol activates the innate immune
      response and TLR4 receptor and causes neuroinflammation, brain damage, and
      cognitive defects in the developmental brain stage of adolescents. We hypothesize
      that by activating the TLR4 response, maternal alcohol consumption during
      pregnancy triggers the release of cytokines and chemokines in both the maternal
      sera and brains of fetuses/offspring, which impairs brain ontogeny and causes
      cognitive dysfunction. METHODS: WT and TLR4-KO female mice treated with or
      without 10% ethanol in the drinking water during gestation and lactation were
      used. Cytokine/chemokine levels were determined by ELISA in the amniotic fluid,
      maternal serum, and cerebral cortex, as well as in the offspring cerebral cortex.
      Microglial and neuronal markers (evaluated by western blotting), myelin proteins
      (immunohistochemical and western blotting) and synaptic parameters (western
      blotting and electron microscopy) were assessed in the cortices of the WT and
      TLR4-KO pups on PND 0, 20, and 66. Behavioral tests (elevated plus maze and
      passive avoidance) were performed in the WT and TLR4-KO mice on PND 66 exposed or
      not to ethanol. RESULTS: We show that alcohol intake during gestation and
      lactation increases the levels of several cytokines/chemokines (IL-1beta, IL-17,
      MIP-1alpha, and fractalkine) in the maternal sera, amniotic fluid, and brains of
      fetuses and offspring. The upregulation of cytokines/chemokines is associated
      with an increase in activated microglia markers (CD11b and MHC-II), and with a
      reduction in some synaptic (synaptotagmin, synapsin IIa) and myelin (MBP, PLP)
      proteins in the brains of offspring on days 0, 20, and 66 (long-term effects).
      These changes are associated with long-term behavioral impairments, in the 66-day
      old alcohol-exposed pups. TLR4-deficient mice are protected against ethanol
      induced cytokine/chemokine production in alcohol-treated dams and offspring,
      along with synaptic and myelin alterations, and the log-term behavioral
      dysfunction induced by ethanol in offspring. CONCLUSIONS: These results suggest
      that the immune system activation, through the TLR4 response, might play an
      important role in the neurodevelopmental defects in FASD.

PMID- 28738880
TI  - Level of mitoses in non-muscle invasive papillary urothelial carcinomas (pTa and
      pT1) at initial bladder biopsy is a simple and powerful predictor of clinical
      outcome: a multi-center study in South Korea.
AB  - BACKGROUND: Histologic grade is the most important predictor of the clinical
      outcome of non-muscle invasive (Ta, T1) papillary urothelial carcinoma (NMIPUCa),
      but its ambiguous criteria diminish its power to predict recurrence/progression
      for individual patients. We attempted to find an objective and reproducible
      histologic predictor of NMIPUCa that correlates well with the clinical outcome.
      METHODS: A total of 296 PUCas were collected from the Departments of Surgical
      Pathology of 11 institutions in South Korea. The clinical outcome was grouped
      into no event (NE), recurrence (R), and progression (P) categories. All 25
      histological parameters were numerically redefined. The clinical pathology of
      each case was reviewed individually by 11 pathologists from 11 institutions based
      on the 2004 WHO criteria and afterwards blindly evaluated by two participants,
      based on our proposed parameters. Univariate and multivariate logistic regression
      analyses were performed using the R software package. RESULTS: The level of
      mitoses was the most reliable parameter for predicting the clinical outcome. We
      propose a four-tiered grading system based on mitotic count (> 10/10 high-power
      fields), nuclear pleomorphism (smallest-to-largest ratio of tumor nuclei >20),
      presence of divergent histology, and capillary proliferation (> 20 capillary
      lumina per papillary core). CONCLUSIONS: The level of mitoses at the initial
      bladder biopsy and transurethral resection (TUR) specimen appeared to be an
      independent predictor of the Ta PUCa outcome. Other parameters include the number
      of mitoses, nuclear pleomorphism, divergent histology, and capillary
      proliferation within the fibrovascular core. These findings may improve selection
      of patients for a therapeutic strategy as compared to previous grading systems.

PMID- 28738881
TI  - Assessment of quality of life in patients with post kalaazar dermal
      leishmaniasis.
AB  - BACKGROUND: Post kala-azar dermal leishmaniasis (PKDL) is a dermatological
      disorder caused by protozoal parasite Leishmania donovani. PKDL cases are thought
      to be a reservoir of parasites and may increase cases of visceral leishmaniasis.
      The disease is not life threatening but cosmetic disfigurement associated with it
      may impair the patients' quality of life. This study aimed to assess the health
      related quality of life in patients with post kalaazar dermal leishmanasis for
      the first time. METHODS: A total of 92 PKDL cases and 96 healthy participants
      filled out the questionnaires. The Dermatology Life Quality Index (DLQI) and SF
      36 questionnaire were used to assess the quality of life. Data on socio
      demographic and clinical features were also collected. The collected data were
      analyzed by using SPSS software (version 16), Student's t-test, analysis of
      variance (ANOVA) was applied for comparison of means. RESULTS: PKDL patients
      experienced very large impact on their quality of life. The mean score of DLQI
      was 11.41. Highest impact was found in symptoms and feelings and lowest impact
      was observed for personal relationship domain. Patients below 20 years age group
      found to have lower quality of life. There was a significant difference in mean
      DLQI scores with regard to age and severity of lesions (P < 0.05). No significant
      difference was observed with respect to gender, duration and location of lesions
      (p > 0.05). CONCLUSION: PKDL significantly impaired the patient's quality of
      life. Further studies to assess the impact of treatment on quality of life in
      these patients are recommended.

PMID- 28738882
TI  - Hemisphere specific EEG related to alternate nostril yoga breathing.
AB  - BACKGROUND: Previously, forced unilateral nostril breathing was associated with
      ipsilateral, or contralateral cerebral hemisphere changes, or no change. Hence it
      was inconclusive. The present study was conducted on 13 normal healthy
      participants to determine the effects of alternate nostril yoga breathing on (a)
      cerebral hemisphere asymmetry, and (b) changes in the standard EEG bands.
      METHODS: Participants were randomly allocated to three sessions (a) alternate
      nostril yoga breathing (ANYB), (b) breath awareness and (c) quiet sitting, on
      separate days. EEG was recorded from bilaterally symmetrical sites (FP1, FP2, C3,
      C4, O1 and O2). All sites were referenced to the ipsilateral ear lobe. RESULTS:
      There was no change in cerebral hemisphere symmetry. The relative power in the
      theta band was decreased during alternate nostril yoga breathing (ANYB) and the
      beta amplitude was lower after ANYB. During quiet sitting the relative power in
      the beta band increased, while the amplitude of the alpha band reduced.
      CONCLUSION: The results suggest that ANYB was associated with greater calmness,
      whereas quiet sitting without specific directions was associated with arousal.
      The results imply a possible use of ANYB for stress and anxiety reduction.

PMID- 28738883
TI  - Recurrent c.G1636A (p.G546S) mutation of COL2A1 in a Chinese family with skeletal
      dysplasia and different metaphyseal changes: a case report.
AB  - BACKGROUND: Mutations in the COL2A1 gene cause type II collagenopathies
      characterized by skeletal dysplasia with a wide spectrum of phenotypic severity.
      Most COL2A1 mutations located in the triple-helical region, and the glycine to
      bulky amino acid substitutions (e.g., glycine to serine) in the Gly-X-Y repeat
      were identified frequently. However, the same COL2A1 mutations are associated
      with different phenotypes and the genotype-phenotype relationship is still poorly
      understood. Therefore, the studies of more patients about the recurrent mutations
      in COL2A1 will be needed for further research to provide more comprehensive
      clinical and genetic data. In this paper, we report a rare recurrent c.G1636A
      (p.G546S) mutation in COL2A1 associated with different metaphyseal changes in a
      Chinese family. CASE PRESENTATION: The proband (III-3) was the second child of
      the family with skeletal dysplasia. She was 2 years and 3 months old with
      disproportional short stature, short neck, pectus carinatum, genu varum,
      bilateral pes planus, and obvious waddling gait. Notably, she displayed severe
      metaphyseal lesions, especially typical "dappling" and "corner fracture"
      appearance, whereas no particular metaphyseal involvement was detected in the
      proband's mother (II-3) and elder sister (III-2) in the family. We identified a
      heterozygous mutation (c.1636G > A) in COL2A1 in the three patients, causing the
      substitution of glycine to serine in codon 546. Although the same mutation has
      been reported in two previous studies, the phenotypes of the previous patients
      were different from those of our patients, and the characteristic "dappling" and
      "corner fracture" metaphyseal abnormalities were not reported previously.
      CONCLUSIONS: In this study, we identified a c.G1636A (p.G546S) mutation in the
      COL2A1 associated with different metaphyseal changes, which was never reported in
      the literature. Our findings revealed a different causative amino acid
      substitution (glycine to serine) associated with the "dappling" and "corner
      fracture" metaphyseal abnormalities, and may provide a useful reference for
      evaluating the phenotypic spectrum and variability of type II collagenopathies.

PMID- 28738884
TI  - Health status and health behaviors among citizen endurance Nordic skiers in the
      United States.
AB  - BACKGROUND: More than two-thirds of Americans are overweight or obese (69%)
      placing them at high risk for a wide array of chronic diseases. Physical activity
      anchors most approaches to obesity prevention and weight management, but physical
      activity levels remain low in the general US population. As a group, citizen
      athletes who compete in Nordic skiing events such as the American Birkebeiner
      participate in fitness cultures that promote physical activity. METHODS: During
      October-November 2014, we emailed a 48 question online survey to 23,611
      individuals who had participated in the American Birkebeiner ski event, the
      largest citizen ski race in North America. Descriptive statistics were used to
      summarize data. Binomial and student t test were used to compare binary and
      continuous outcomes to health behaviors of the US population. RESULTS: 5433
      individuals responded. Obesity prevalence (BMI >=30) was 3% and average BMI was
      24. Skiers reported very good health (88%), higher fitness than peers (99%),
      freedom from depression (93%) low levels of smoking (3%), high consumption of
      fruits and vegetables, moderate alcohol use, and high levels of physical
      activity. Fifteen percent practiced all 4 healthy living characteristics known to
      reduce cardiovascular event risk. CONCLUSIONS: As a group, citizen endurance
      Nordic skiers enjoy low levels of obesity, below average BMI, and report
      lifestyle behaviors known to decrease obesity, promote health, and reduce
      cardiovascular disease risk. Future research should explore hypotheses that
      explain how the fitness cultures surrounding citizen athletic events support
      weight loss, cardiovascular fitness, and healthy lifestyle habits.

PMID- 28738886
TI  - Failure to return to receive HIV-test results: the Cameroon experience.
AB  - BACKGROUND: To be acquainted of one's HIV serological status is an important
      strategy for the fight against HIV/AIDS, but many patients still miss the
      appointment to receive their HIV-test result. The aim of this study was to
      determine the epidemiological and serological profiles of patients not coming
      back to collect their HIV-test result in a tertiary health care facility in
      Yaounde, Cameroon. METHODS: We undertook a retrospective analysis of data of
      patients who visited the HIV-day care unit of the Yaounde Central Hospital
      (Yaounde, Cameroon) from January to December 2009 in order to be screened for
      HIV, and who did not come back to retrieve their result. RESULTS: Of the 3990
      patients who visited the unit during the study period, 396 (9.92%) did not come
      back to collect their HIV-test result, of whom 21% were aged 26-30 years
      representing the most encountered age group. Females (57.8%) were significantly
      more present than males (p = 0.023). More than half of these patients (54.9%)
      visited the unit for a voluntary HIV testing. Two hundred and three patients
      (51.3%) had a positive HIV-test result, of whom 63.5% were females. The most HIV
      infected group was the one coming for a voluntary screening (36.5%). Women not
      returning to receive their results were more likely to be tested HIV-positive
      (odds ratio = 1.62, 95% confidence interval: 1.08-2.42; p < 0.05). CONCLUSIONS:
      Almost 10% of patients screened for HIV infection did not come back to collect
      their result. More strategies should be implemented to reduce this rate,
      especially targeting young adults (20-35 years) and women. The delay in
      delivering patients' results should be shortened. Concurrently, there is need to
      increase voluntary HIV-testing in our settings.

PMID- 28738885
TI  - Differential effects of FTY720 on the B cell compartment in a mouse model of
      multiple sclerosis.
AB  - BACKGROUND: MP4-induced experimental autoimmune encephalomyelitis (EAE) is a
      mouse model of multiple sclerosis (MS), which enables targeted research on B
      cells, currently much discussed protagonists in MS pathogenesis. Here, we used
      this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod)
      on the autoreactive B cell and antibody response both in the periphery and the
      central nervous system (CNS). METHODS: MP4-immunized mice were treated orally
      with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The
      subsequent disease course was monitored and the MP4-specific B cell/antibody
      response was measured by ELISPOT and ELISA. RNA sequencing was performed to
      determine any effects on B cell-relevant gene expression. S1P1 receptor
      expression by peripheral T and B cells, B cell subset distribution in the spleen
      and B cell infiltration into the CNS were studied by flow cytometry. The
      formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was
      evaluated by histology and immunohistochemistry. Potential direct effects of
      FTY720 on B cell aggregation were studied in vitro. RESULTS: FTY720 significantly
      attenuated clinical EAE when treatment was initiated at the peak of EAE. While
      there was a significant reduction in the number of T cells in the blood after
      FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence
      for the modulation of B cell receptor-mediated signaling upon FTY720 treatment.
      In addition, we detected a significant increase in the percentage of B220+ B
      cells in the spleen both in acute and chronic EAE. Whereas acute treatment
      completely abrogated B cell aggregate formation in the CNS, the numbers of
      infiltrating B cells and plasma cells were comparable between vehicle- and FTY720
      treated mice. In addition, there was no effect on already developed aggregates in
      chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct
      effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of
      B cell aggregates into TLOs. CONCLUSIONS: The data suggest differential effects
      of FTY720 on the B cell compartment in MP4-induced EAE.

PMID- 28738887
TI  - Emerging technologies in autoantibody testing for rheumatic diseases.
AB  - Testing for the presence of antinuclear antibodies (ANAs) is a key step in the
      diagnosis of systemic lupus erythematosus (SLE) and other systemic autoimmune
      rheumatic diseases (SARD). The standard slide-based indirect immunofluorescence
      (IIF) test is widely used, but is limited by a relative lack of specificity for
      SLE and not all SARD-ANAs are detected. Alternative immunoassays that might offer
      enhanced diagnostic and prognostic information have evolved, and some of these
      have entered clinical practice. This review summarizes the current state of ANA
      testing and multiplex techniques for detecting other autoantibodies, the
      possibility of point-of-care testing, and approaches for applications in early
      disease stages.

PMID- 28738888
TI  - Genetic characterization of 11 porcine reproductive and respiratory syndrome
      virus isolates in South China from 2014 to 2015.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) has leaded to an
      enormous loss per year to the swine industry, its etiology porcine reproductive
      and respiratory syndrome virus (PRRSV) is a highly mutated virus in pigs. To
      fully understand the genetic characteristics of PRRSV genome in South China, this
      study collected the lung samples infected with PRRSV in Guangdong and Hainan
      province from 2014 to 2015 and tried to isolate the PRRSV. Finally, the complete
      genomes of isolated strains were sequenced and analyzed. METHODS: Virus isolation
      was performed in MARC-145 cells. The 13 fragments of PRRSV genome were amplified
      by RT-PCR and the complete PRRSV genome sequence was obtained by SeqMan program
      of DNASTAR7.0 software. Nucleotide and deduced amino acid (AA) sequences of NSP2
      and ORF5 were aligned using the MegAlign program of DNASTAR7.0 software to
      determine sequence homology. A phylogenetic tree was constructed using MEGA5.2
      software with the neighbor-joining method to analyze the evolutionary
      relationship. RESULTS: 11 PRRSV strains were isolated in South China from 2014 to
      2015. All the isolated strains clustered into subgenotype V along with the HP
      PRRSV representative strains JXA1, HuN4 and JXwn06. The subgenotype V was
      furtherly divided into two groups. AA sequence alignment analysis indicated that
      all the isolated strains had 1 AA deletion and 29 AA continuous deletion at
      position 481 and 533-561. Notably, GDHY strain had another 120 AA continuous
      deletion at position 629-748. All the isolated strains had an A137S mutation in
      the residue A137 of GP5 which was considered to differentiate vaccine strains.
      All the isolated strains had a L39I mutation in the primary neutralizing epitope
      (PNE) of GP5. Except GDHZ had a N34T mutation, all the other isolated strains had
      conserved N30, N44 and N51 glycosylation sites in the four potential N
      glycosylation sites (N30, N34, N44 and N51) of GP5. CONCLUSIONS: Our study showed
      that the prevalent strains in this region were highly pathogenic PRRS virus-like.
      Moreover, one new strain having another 120 amino acids continuous deletion
      except the discontinuous 30 (29+1) amino acids deletion in NSP2 region had
      emerged. Besides, the isolated strains had extensive amino acids substitutions in
      the putative signal, extravirion and intravirion regions of GP5. These results
      showed that PRRSV has undergone extensive variation in South China, providing
      some theoretical basis for researching effective vaccince to better controling
      the PRRSV in this area.

PMID- 28738889
TI  - Influence of the pneumococcal conjugate vaccines on the temporal variation of
      pneumococcal carriage and the nasal microbiota in healthy infants: a longitudinal
      analysis of a case-control study.
AB  - BACKGROUND: Bacterial colonization of the upper airways is a prerequisite for
      subsequent invasive disease. With the introduction of the 7- and 13-valent
      pneumococcal conjugate vaccines (PCV7 and PCV13), changes in pneumococcal upper
      airway colonization have been described. It is, however, less evident whether the
      vaccines lead to compositional changes of the upper airway microbiota. Here, we
      performed a case-control study using samples from a longitudinal infant cohort
      from Switzerland. We compared pneumococcal carriage and the nasal microbiota
      within the first year of life of healthy infants vaccinated with either PCV7 (n =
      20, born in 2010) or PCV13 (n = 21, born between 2011 and 2013). Nasal swabs were
      collected every second week (n = 763 in total). Pneumococcal carriage was
      analyzed by quantitative PCR of the pneumococcal-specific lytA gene. Analysis of
      the bacterial core microbiota was performed based on 16S rRNA sequencing and
      subsequent oligotyping. We exclusively performed oligotyping of the core
      microbiota members, which were defined as the five most abundant bacterial
      families (Moraxellaceae, Streptococcaceae, Staphylococcaceae, Corynebacteriaceae,
      and Pasteurellaceae). Linear mixed effect (LME) and negative binomial regression
      models were used for statistical analyses. RESULTS: We found a higher number of
      samples positive for pneumococcal carriage in PCV7- compared to PCV13-vaccinated
      infants (LME model; P = 0.01). In contrast, infants vaccinated in the PCV13 era
      had an increased alpha diversity as measured by the richness and the Shannon
      Diversity Index (LME model; P = 0.003 and P = 0.01, respectively). Accordingly,
      the PCV13 era was associated with clusters of a higher diversity than PCV7
      associated clusters. Furthermore, infants vaccinated with PCV13 had a higher
      binary-based within-subject microbiota similarity, as well as a decreased Jensen
      Shannon distance over time as compared to PCV7-vaccinated infants, indicating a
      higher microbiota stability in the PCV13 era (LME model and t test; P = 0.06 and
      P = 0.03, respectively). CONCLUSIONS: We hypothesize that the higher diversity
      and stability of the upper airway microbiota in the PCV13 era is the result of
      the lower pneumococcal carriage rate. This seems to indicate that the nasal
      bacterial microbiota of infants has changed in recent years as compared to the
      beginning of this study.

PMID- 28738891
TI  - Pivotal trials of orthopedic surgical devices in the United States: predominance
      of two-arm non-inferiority designs.
AB  - BACKGROUND: The United States Food and Drug Administration (FDA) reviews class
      III orthopedic devices submitted for premarket approval with pivotal clinical
      trials. The purpose of this study was to determine the types of orthopedic
      devices reviewed, the design of their pivotal clinical trials, and the subjective
      factors affecting the interpretation of clinical trial data. METHODS: Meetings of
      the FDA Orthopaedic and Rehabilitation Devices Panel were identified from 2000
      2016. Meeting materials were collected from FDA electronic archives and notes
      were made regarding the device-type and subsequent approval and recall, the
      design of pivotal clinical trials, and issues of trial interpretation debated
      during panel deliberations. RESULTS: The panel was convened on 29 separate
      occasions over the course of 35 days to deliberate 38 distinct topics. Of these,
      23 topics included clinical data submitted for approval of a device, and two
      topics were excluded. Of the 23 devices, five were biologic, three were hip
      arthroplasty, three were disc arthroplasty, two were viscosupplementation, three
      were interspinous process devices, and seven were other devices. Of the 23
      pivotal trials, 20 (87.0%) were randomized controlled trials (RCTs), consisting
      of 13 (65.0%) non-inferiority trials and 7 (35.0%) superiority trials, and all
      RCTs were two-arm trials. At panel, the most commonly debated issues were related
      to the design and interpretation of non-inferiority trials. CONCLUSIONS: A broad
      array of device types is reviewed by the FDA. The predominance of two-arm non
      inferiority trials as pivotal studies indicates that the nuances of their design
      and interpretation are commercially important.

PMID- 28738890
TI  - An examination of Australian newspaper coverage of the link between alcohol and
      cancer 2005 to 2013.
AB  - BACKGROUND: Alcohol is a Class-1 carcinogen but public awareness of the link
      between alcohol and cancer is low. The news media is a popular, readily
      accessible source of health information and plays a key role in shaping public
      opinion and influencing policy-makers. Examination of how the link between
      alcohol and cancer is presented in Australian print media could inform public
      health advocacy efforts to raise awareness of this modifiable cancer risk factor.
      METHOD: This study provides a summative qualitative content analysis of 1502
      articles that included information about a link between alcohol and cancer, as
      reported within Australian newspaper media (2005-2013). We use descriptive
      statistics to examine the prominence of reports, the nature and content of claims
      regarding the link between alcohol and cancer, and the source of information
      noted in each article. RESULTS: Articles were distributed throughout newspapers,
      most appearing within the main (first) section. The link between alcohol and
      cancer tended not to appear early in articles, and rarely featured in headlines.
      95% of articles included a claim that alcohol causes cancer, 5% that alcohol
      prevented or did not cause cancer, 1% included both. Generally, the amount of
      alcohol that would cause or prevent cancer was unspecified or open to subjective
      interpretation. Coverage increased over time, primarily within community/free
      papers. The claim that alcohol causes cancer often named a specific cancer, did
      not name a specific alcohol, was infrequently the focus of articles (typically
      subsumed within an article on general health issues), and cited various health
      promoting (including advocacy) organisations as information sources. Articles
      that included the converse also tended not to focus on that point, often named a
      specific type of alcohol, and most cited research institutions or generic
      'research' as sources. Half of all articles involved repetition of materials, and
      most confirmed that alcohol caused cancer. CONCLUSIONS: Information about a link
      between alcohol and cancer is available in the Australian newsprint media, but
      may be hidden within and thus overshadowed by other health-related stories.
      Strategic collaboration between health promoting organisations, and exploitation
      of 'churnalism' and journalists' preferences for ready-made 'copy' may facilitate
      increased presence and accuracy of the alcohol-cancer message.

PMID- 28738892
TI  - Challenges to replace ACT as first-line drug.
AB  - The spread of artemisinin and partner drug resistance through Asia requires
      changes in first-line therapy. The traditional modus has been the replacement of
      one first-line anti-malarial regimen with another. The number of anti-malarial
      drug candidates currently in development may have given false confidence in the
      expectation that resistance to artemisinin-based combination therapy (ACT) can be
      solved with a switch to the next anti-malarial drug regimen. A number of
      promising anti-malarial drug regimens did not succeed in becoming first-line
      drugs due to safety concerns or rapid development of resistance. Currently
      promising candidates for inclusion in first-line regimens, such as KAE 609, KAF
      156, OZ 439, and OZ 277, have already triggered safety concerns or fears that
      point mutations could render the drugs inefficacious. An additional challenge for
      a new first-line drug is finding an appropriate partner drug. There is hope that
      none of the above-mentioned concerns will be substantiated in larger, upcoming
      trials. Meanwhile, combining already licensed anti-malarials may be a promising
      stop-gap measure. Practitioners in Vietnam have empirically started to add
      mefloquine to the current dihydroartemisinin-piperaquine. Practitioners in Africa
      could do worse than empirically combine already licensed co-artemether and
      amodiaquine when treatment with ACT no longer clears Plasmodium falciparum. Both
      combinations are currently undergoing trials.

PMID- 28738893
TI  - Anaphylaxis with delayed appearance of skin manifestations during general
      anesthesia: two case reports.
AB  - BACKGROUND: Anaphylaxis is difficult to diagnose in the absence of skin or
      mucosal signs and symptoms. We report two cases of anaphylaxis under general
      anesthesia, in which the initial presentation was in the form of respiratory
      signs, followed by skin manifestations 10-15 min later. Diagnosis of anaphylaxis
      was delayed because skin symptoms were absent early on in the presentation. CASE
      PRESENTATION: In the first case, a 23-year-old male patient with jaw deformity
      was scheduled to undergo maxillary alveolar osteotomy. After intubation,
      auscultation indicated a sudden decrease in breath sounds, together with severe
      hypotension. Approximately 10 min later, flushing of the skin and urticaria on
      the thigh appeared and spread widely throughout the body. In the second case, a
      21-year-old female patient with jaw deformity was scheduled to undergo
      maxillomandibular osteotomy. Twenty minutes after the start of dextran infusion,
      her lungs suddenly became difficult to ventilate, and oxygen saturation decreased
      to 90%. Approximately 15 min later, flushing of the skin and urticaria were
      observed. CONCLUSION: In both cases, there was a time lag between the appearance
      of respiratory and skin symptoms, which resulted in a delay in the diagnosis, and
      hence, treatment of anaphylaxis. Our experience highlights the fact that it is
      difficult to diagnose anaphylaxis under general anesthesia.

PMID- 28738894
TI  - Occupational exposure to chlorinated solvents and risk of head and neck cancer in
      men: a population-based case-control study in France.
AB  - BACKGROUND: Few epidemiological studies have investigated the link between
      occupational exposure to solvents and head and neck cancer risk, and available
      findings are sparse and inconsistent. The objective of this study was to examine
      the association between occupational exposure to chlorinated solvents and head
      and neck cancer risk. METHODS: We analyzed data from 4637 men (1857 cases and
      2780 controls) included in a population-based case-control study, ICARE (France).
      Occupational exposure to five chlorinated solvents (perchloroethylene [PCE],
      trichloroethylene [TCE], methylene chloride [MC], chloroform [CF], and carbon
      tetrachloride [CT]) was assessed through job-exposure matrices. Odds ratios (ORs)
      and confidence intervals (95% CI) were estimated by unconditional logistic
      regression, adjusted for age, tobacco smoking, alcohol consumption, asbestos
      exposure, and other potential confounders. RESULTS: We observed no association
      between chlorinated solvent exposure and head and neck cancer risk, despite a non
      significant increase in risk among subjects who had the highest cumulative level
      of exposure to PCE, (OR = 1.81; 95% CI = 0.68 to 4.82). In subsite analysis, the
      risk of laryngeal cancer increased with cumulative exposure to PCE (p for trend =
      0.04). The OR was 3.86 (95% CI = 1.30 to 11.48) for those exposed to the highest
      levels of PCE. A non-significant elevated risk of hypopharyngeal cancer was also
      observed in subjects exposed to the highest levels of MC (OR = 2.36; 95% CI =
      0.98 to 5.85). CONCLUSION: Our findings provide evidence that high exposure to
      PCE increases the risk of laryngeal cancer, and suggest an association between
      exposure to MC and hypopharyngeal cancer. Exposure to other chlorinated solvents
      was not associated with the risk of head and neck cancer.

PMID- 28738895
TI  - Chiropractic spinal manipulative therapy for cervicogenic headache: a single
      blinded, placebo, randomized controlled trial.
AB  - OBJECTIVE: Cervicogenic headache is a disabling headache where pharmacological
      management have limited effect. Thus, non-pharmacological management is
      warranted. Our objective was therefore to investigate the efficacy of
      chiropractic spinal manipulative therapy versus placebo (sham manipulation) and
      control (continued usual but non-manual management) for cervicogenic headache in
      a prospective 3-armed single-blinded, placebo, randomized controlled trial of 17
      months' duration. RESULTS: Nineteen participants were equally randomized into the
      three groups, and 12 participants completed the randomized controlled trial.
      Headache frequency improved at all time points in the chiropractic spinal
      manipulative therapy and the placebo group. Headache index improved in the
      chiropractic spinal manipulative therapy group at all time points, while it
      improved at 6 and 12 months' follow-up in the placebo group. The control group
      remained unchanged during the whole study period. Adverse events were few, mild
      and transient. Blinding was concealed throughout the RCT. Thus, our results
      suggest that manual-therapy might be a safe treatment option for participants
      with cervicogenic headache, but data need to be confirmed in a randomized
      controlled trial with sufficient sample size and statistical power. Trial
      registration ClinicalTrials.gov identifier: NCT01687881, 11 September 2012.

PMID- 28738896
TI  - Real-time reverse transcription PCR-based sequencing-independent pathotyping of
      Eurasian avian influenza A viruses of subtype H7.
AB  - Low pathogenic avian influenza viruses (LPAIV) of the subtypes H5 and H7 are
      known to give rise to highly pathogenic (HP) phenotypes by spontaneous
      insertional mutations which convert a monobasic trypsin-sensitive
      endoproteolytical cleavage site (CS) within the hemagglutinin (HA) protein into a
      polybasic subtilisin-sensitive one. Sporadic outbreaks of notifiable LPAIV H7
      infections are continuously recorded in Europe and in Asia, and some lineages
      showed zoonotic transmission. De novo generation of HPAIV H7 from LPAIV
      precursors has been reported several times over the past decade. Rapid
      differentiation between LP and HP H7 virus strains is required as a prerequisite
      to emplace appropriate control measures. Here, reverse transcription real-time
      PCR assays (RT-qPCR) were developed and evaluated that allow LP and HP pathotype
      identification and distinction by probe-assisted detection of the HACS. These new
      RT-qPCRs allow a sensitive and highly specific pathotype identification of
      Eurasian subtype H7 AIV in allantoic fluids as well as in diagnostic field
      samples. RT-qPCR assisted pathotyping presents a rapid and sensitive alternative
      to pathotyping by animal inoculation or nucleotide sequencing.

PMID- 28738897
TI  - Food assistance is associated with decreased nursing home admissions for
      Maryland's dually eligible older adults.
AB  - BACKGROUND: Although it has long been known that a broad range of factors beyond
      medical diagnoses affect health and health services use, it has been unclear
      whether additional income can decrease health service use. We examined whether
      Supplemental Nutrition Assistance Program (SNAP) receipt is associated with
      subsequent nursing home entry among low income older adults. METHODS: We examined
      the 77,678 older adults dually eligible for Medicaid and Medicare in Maryland,
      2010-2012. Zero inflated negative binomial regression, adjusting for demographic
      and health factors, tested the association of either lagged SNAP enrollment or
      lagged benefit amount with nursing home admission. We used Heckman two-step model
      results to calculate potential savings of SNAP enrollment through reduced nursing
      home admissions and reduced duration. RESULTS: Only 53.4% received SNAP in 2012,
      despite being income-eligible. SNAP participants had a 23% reduced odds of
      nursing home admission than nonparticipants (95% CI: 0.75-0.78). For SNAP
      participants, an additional $10 of monthly SNAP assistance was associated with
      lower odds of admission (OR = 0.93, 95% CI: 0.93-0.93), and fewer days stay among
      those admitted (IRR = 0.99, 95% CI: 0.98-0.99). Providing SNAP to all 2012 sample
      nonparticipants could be associated with $34 million in cost savings in Maryland.
      CONCLUSIONS: SNAP is underutilized and may reduce costly nursing home use among
      high-risk older adults. This study has policy implications at the State and
      Federal levels which include expanding access to SNAP and enhancing SNAP amounts.

PMID- 28738898
TI  - Silicanin-1 is a conserved diatom membrane protein involved in silica
      biomineralization.
AB  - BACKGROUND: Biological mineral formation (biomineralization) proceeds in
      specialized compartments often bounded by a lipid bilayer membrane. Currently,
      the role of membranes in biomineralization is hardly understood. RESULTS:
      Investigating biomineralization of SiO2 (silica) in diatoms we identified
      Silicanin-1 (Sin1) as a conserved diatom membrane protein present in silica
      deposition vesicles (SDVs) of Thalassiosira pseudonana. Fluorescence microscopy
      of GFP-tagged Sin1 enabled, for the first time, to follow the intracellular
      locations of a biomineralization protein during silica biogenesis in vivo. The
      analysis revealed incorporation of the N-terminal domain of Sin1 into the
      biosilica via association with the organic matrix inside the SDVs. In vitro
      experiments showed that the recombinant N-terminal domain of Sin1 undergoes pH
      triggered assembly into large clusters, and promotes silica formation by
      synergistic interaction with long-chain polyamines. CONCLUSIONS: Sin1 is the
      first identified SDV transmembrane protein, and is highly conserved throughout
      the diatom realm, which suggests a fundamental role in the biomineralization of
      diatom silica. Through interaction with long-chain polyamines, Sin1 could serve
      as a molecular link by which the SDV membrane exerts control on the assembly of
      biosilica-forming organic matrices in the SDV lumen.

PMID- 28738899
TI  - A rare manifestation of burns after lightning strike in rural Ghana: a case
      report.
AB  - BACKGROUND: Lightning is a natural phenomenon that mostly affects countries in
      the tropical and subtropical regions of the globe, including Ghana. Lightning
      strikes pose a global public health issue. Although strikes to humans are
      uncommon, it is associated with high morbidity and mortality. CASE PRESENTATION:
      We present a case of a 10-year-old Ghanaian girl who got second-degree burns
      after being struck by lightning. She was put on an intravenous broad-spectrum
      antibiotic (ceftriaxone), Ringer's lactate, and her burns were dressed with
      sterile gauze impregnated with Vaseline (petroleum jelly) and silver sulfadiazine
      ointment. There was marked improvement on the 16th day of treatment despite the
      lack in capacity of the hospital to carry out some laboratory diagnostic tests.
      On the 21st day of treatment, the burns were completely healed without scars and
      contractures. CONCLUSIONS: This is evidence of burns due to lightning strike,
      despite its rare occurrence. This report will help inform those in doubt,
      particularly in communities where lightning injuries are associated with
      widespread superstition. The case report also revealed how rural healthcare can
      be challenging amid a lack of basic diagnostic equipment and logistics. However,
      in resource-limited settings, Vaseline (petroleum jelly) and silver sulfadiazine
      could be used in the treatment of burns.

PMID- 28738900
TI  - Impact of ablation duration on rhythm outcome after concomitant maze procedure
      using cryoablation in patients with persistent atrial fibrillation.
AB  - BACKGROUND: The aim of this study was to evaluate the impact of ablation duration
      during a maze procedure using a nitrous oxide-based cryosurgical system. METHODS:
      From May 2001 to December 2006, 256 consecutive patients who underwent a
      concomitant maze procedure using nitrous oxide-based cryoablation for chronic
      atrial fibrillation (AF) during cardiac surgery were enrolled. The ablation
      duration for each lesion was between 120 s at -60  degrees C in 140 patients
      (control group) and 160 s in 116 patients (long duration group). RESULTS: One in
      hospital death occurred, and a permanent pacemaker was implanted in one patient
      (0.4%). At discharge, absence of AF was noted in 84.5% of the long duration group
      and in 87.1% of the control group. During follow up, patients in the long
      duration group achieved and maintained the absence of AF at a higher rate than
      the control patients (96% vs. 84% at 24 months, respectively: P = 0.008).
      Multivariable analysis identified long AF duration as the only independent
      predictor of AF recurrence. At late follow up, left atrial mechanical activity
      was less frequent in the control group than in the long duration group. The mean
      left atrial volume index was lower in the long duration group than in the control
      group. CONCLUSION: The modified cryomaze procedure is safe and effective.
      Ablation time plays an important role in achieving and maintaining the absence of
      AF. Long cryoablation duration is recommended for optimal cryomaze results.

PMID- 28738901
TI  - Stroke in a resource-constrained hospital in Madagascar.
AB  - BACKGROUND: Stroke is reported as the most frequent cause of in-hospital death in
      Madagascar. However, no descriptive data on hospitalized stroke patients in the
      country have been published. In the present study, we sought to investigate the
      feasibility of collecting data on stroke patients in a resource-constrained
      hospital in Madagascar. We also aimed to characterize patients hospitalized with
      stroke. METHODS: We registered socio-demographics, clinical characteristics, and
      early outcomes of patients admitted for stroke between 23 September 2014 and 3
      December 2014. We used several validated scales for the evaluation. Stroke
      severity was measured by the National Institutes of Health Stroke Scale (NIHSS),
      disability by the modified Rankin Scale (mRS), and function by the Barthel Index
      (BI). RESULTS: We studied 30 patients. Sixteen were males. The median age was
      62.5 years (IQR 58-67). The NIHSS and mRS were completed for all of the patients,
      and BI was used for the survivors. Three patients received a computed tomography
      (CT) brain scan. The access to laboratory investigations was limited.
      Electrocardiographs (ECGs) were not performed. The median NIHSS score was 16.5
      (IQR 10-35). The in-hospital stroke mortality was 30%. At discharge, the median
      mRS score was 5 (IQR 4-6), and the median BI score was 45 (IQR 0-72.5).
      CONCLUSIONS: Although the access to brain imaging and supporting investigations
      was deficient, this small-scale study suggests that it is feasible to collect
      essential data on stroke patients in a resource-constrained hospital in
      Madagascar. Such data should be useful for improving stroke services and planning
      further research. The hospitalized stroke patients had severe symptoms. The in
      hospital stroke mortality was high. At discharge, the disability category was
      high, and functional status low.

PMID- 28738902
TI  - A comparative effectiveness study of two culturally competent models of diabetes
      self-management programming for Latinos from low-income households.
AB  - BACKGROUND: Diabetes risk is extremely high for Latinos from low-income
      households. Health guidelines recommend that individuals learn strategies to self
      manage their diabetes, but getting people to adopt required lifestyle changes is
      challenging and many people are not able to prevent their pre-diabetes from
      escalating or effectively control their diabetes. Systematic reviews show that
      culturally competent self-management programs can significantly improve diabetes
      outcomes and different models for culturally competent programming have been
      developed. METHODS: This patient-engaged study will compare the effectiveness of
      two distinct evidence-based models for culturally competent diabetes health
      promotion at two sites that serve a large Latino patient population from low
      income households: 1) The Diabetes Self-Management Support Empowerment Model, an
      educational session approach, and 2) The Chronic Care Model, a holistic community
      based program. Data collection will involve interviews, focus groups, surveys and
      assessments of each program; and testing of patient participants for A1c,
      depression, Body Mass Index (BMI), and chronic stress with hair cortisol levels.
      We will recruit a total of 240 patient-social support pairs: Patients will be
      adults (men and women over the age of 18) who: 1.) Enter one of the two diabetes
      programs during the study; 2.) Self-identify as "Latino;" 3.) Are able to
      identify a social support person or key member of their social network who also
      agrees to participate with them; 4.) Are not pregnant (participants who become
      pregnant during the study will be excluded); and 5.) Have household income 250%
      of the Federal Poverty Level (FPL) or below. Social supports will be adults who
      are identified by the patient participants. PRIMARY OUTCOME: Improved capacity
      for diabetes self-management measured through improvements in diabetes knowledge
      and diabetes-related patient activation. SECONDARY OUTCOME: Successful diabetes
      self-management as measured by improvements in A1c, depression scale scores, BMI,
      and circulating levels of cortisol to determine chronic stress. DISCUSSION: Our
      hypothesis is that the program model that interfaces most synergistically with
      patients' culture and everyday life circumstances will have the best diabetes
      health outcomes. TRIAL REGISTRATION: This study was registered with
      ClinicalTrials.gov on December 16, 2016 (Registration # NCT03004664 ).

PMID- 28738903
TI  - Erratum to: The role of PPAR activation during the systemic response to brain
      injury.

PMID- 28738904
TI  - Increased interleukin-27 cytokine expression in the central nervous system of
      multiple sclerosis patients.
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disorder characterized by
      chronic inflammation, demyelination, and neuronal damage. During autoimmunity,
      cytokines are important mediators of the inflammation. In this line, interleukin
      27 (IL-27) modulates inflammation and can be produced directly at inflammatory
      sites such as in the joints during rheumatoid arthritis or in the central nervous
      system (CNS) during MS. While in animal models of MS, treatment with IL-27
      decreases the disease severity, its role in humans is not clearly established and
      it is not known if IL-27 could be detected in the cerebrospinal fluid (CSF) of MS
      patients. METHODS: In this study, we measured IL-27 levels using a quantitative
      enzyme-linked immunosorbent assay in CSF of patients with relapsing remitting
      multiple sclerosis (RRMS), isolated optic neuritis (ON) and non-inflammatory
      neurological disease (NIND) as well as in the sera of healthy donors (HD) and
      RRMS patients undergoing different disease modifying treatments. We further
      confirmed by immunohistology of patient biopsies the identity of IL-27 producing
      cells in the brain of active MS lesions. RESULTS: We observed that IL-27 levels
      are increased in the CSF but not in the sera of RRMS compared to HD. We confirmed
      that IL-27 is expressed in active MS plaques by astrocytes of MS patients.
      CONCLUSIONS: Our results point toward a local secretion of IL-27 in the CNS that
      is increased during autoimmune processes. We propose that local production of IL
      27 could sign the induction of a regulatory response that promotes inflammation's
      resolution. The effect of new immunomodulatory therapies on cerebral IL-27
      production could be used to understand the biology of IL-27 in MS disease.

PMID- 28738906
TI  - Next-generation sequencing to monitor the spread of antimicrobial resistance.
AB  - Next-generation sequencing is increasingly being used to monitor current and
      historic events related to the emergence and spread of antimicrobial resistance.
      In a recent publication, researchers analyzed the rise of methicillin-resistant
      Staphylococcus aureus in the 1960s, emphasizing that adaptations conferring
      antibiotic resistance might pre-date the introduction of novel antibiotic
      derivatives. Other researchers have evaluated the role of transmission within a
      healthcare network, using the example of extended-spectrum beta-lactamase
      resistant Escherichia coli.Please see related Genome Biology Research article:
      www.dx.doi.org/10.1186/s13059-017-1252-9 and Genome Medicine Research article:
      www.dx.doi.org/10.1186/s13073-017-0457-6.

PMID- 28738905
TI  - Visceral fat mass: is it the link between uric acid and diabetes risk?
AB  - BACKGROUND: Uric acid (UA) has been suggested as a novel risk factor for
      diabetes. However, its definite role in this prevalent disease is still the
      subject of much discussion because it is always accompanied with other major risk
      factors such as obesity and high visceral adiposity. In order to clarify the role
      of UA in diabetes, this study aimed to investigate the associations between
      plasma UA and fasting plasma glucose, HbA1c, lipid profile and inflammatory
      markers after accounting for the contribution of other diabetes risk factors such
      as BMI and VAT fat mass. METHODS: In the present cross-sectional study, 100 non
      diabetic middle-aged males (n = 48) and females (n = 52) were recruited. Central
      fat distribution measures including android to gynoid fat ratio, VAT and
      subcutaneous adipose tissue (SAT) fat mass were determined using dual-energy X
      ray absorptiometry (DXA). Biochemical analysis was done using methods well
      established for clinical and research laboratories. Multiple linear regression
      analysis was performed to analyse the association between plasma UA and the
      biochemical and central fat distribution measures. RESULTS: UA was positivly
      associated with body mass index (BMI) (r (98) = 0.42, P <= 0.001), android to
      gynoid fat ratio (r (98) = 0.62, P <= 0.001) and VAT fat mass (r (96) = 0.55, P
      <= 0.001). UA was also positively associated with plasma glucose (r (98) = 0.33,
      P <= 0.001), hemoglobin A1c (r (93) = 0.25, P = 0.014), plasma triglyceride (r s
      (95) = 0.40, P <= 0.001), HDL cholesterol (r (98) = - 0.61, P <= 0.001) and CRP
      (r s (98) = 0.23, P = 0.026). However, these associations were no longer
      significant after accounting for BMI or/and VAT fat mass. No significant
      association was observed between UA and SAT fat mass (r (97) = 0.02, P >= 0.05),
      Total cholesterol (r (98) = 0.03, P >= 0.05), LDL cholesterol (r (98) = 0.13, P
      >= 0.05), TNF-alpha (r (97) = 0.12, P >= 0.05) and IL-6 (r (96) = -0.02, P >=
      0.05). CONCLUSION: Results from this study suggest, for the first time, that the
      association between plasma UA and glucose in a non-diabetic population is not
      direct but rather dependent on VAT fat mass.

PMID- 28738908
TI  - Barriers to and facilitators of ultra-processed food consumption: perceptions of
      Brazilian adults.
AB  - OBJECTIVE: To explore how individuals perceive the availability of ultra
      processed foods in their neighbourhoods and the barriers to and facilitators of
      consumption of such foods. DESIGN: A qualitative design was chosen. In-depth,
      face-to-face semi-structured interviews were conducted and a content analysis was
      performed. SETTING: Sao Paulo, Brazil. SUBJECTS: A purposeful sample of adults (n
      48), stratified by sex and age group (20-39 years and 40-59 years). RESULTS: All
      participants perceived their neighbourhoods as favourable regarding the
      availability of ultra-processed foods. Three barriers were identified: health
      concerns, not appreciating the taste of these foods and not being used to eating
      them. Five facilitators, however, were identified: appreciating the taste of
      these foods, their children's preference, convenience, addiction and cost.
      CONCLUSIONS: Participants perceived their neighbourhoods as favourable to the
      consumption of ultra-processed foods and reported more facilitators than barriers
      to their consumption. Reported barriers point to the need to include measures
      promoting a healthy food system and traditional eating practices. The
      facilitators reinforce the idea that these foods are habit-forming and that
      regulatory measures to offset the exposure to ultra-processed foods are
      necessary.

PMID- 28738907
TI  - RIG-I expression in perifascicular myofibers is a reliable biomarker of
      dermatomyositis.
AB  - BACKGROUND: Dermatomyositis (DM) is inflammatory myopathy or myositis
      characterized by muscle weakness and skin manifestations. In the differential
      diagnosis of DM the evaluation of the muscle biopsy is of importance among other
      parameters. Perifascicular atrophy in the muscle biopsy is considered a hallmark
      of DM. However, perifascicular atrophy is not observed in all patients with DM
      and, conversely, perifascicular atrophy can be observed in other myositis such as
      antisynthetase syndrome (ASS), complicating DM diagnosis. Retinoic acid inducible
      gene I (RIG-I), a receptor of innate immunity that promotes type I interferon,
      was observed in perifascicular areas in DM. We compared the value of RIG-I
      expression with perifascicular atrophy as a biomarker of DM. METHODS: We studied
      by immunohistochemical analysis the expression of RIG-I and the presence of
      perifascicular atrophy in 115 coded muscle biopsies: 44 patients with DM, 18 with
      myositis with overlap, 8 with ASS, 27 with non-DM inflammatory myopathy (16 with
      polymyositis, 6 with inclusion body myositis, 5 with immune-mediated necrotizing
      myopathy), 8 with muscular dystrophy (4 with dysferlinopathy, 4 with
      fascioscapulohumeral muscle dystrophy) and 10 healthy controls. RESULTS: We found
      RIG-I-positive fibers in 50% of DM samples vs 11% in non-DM samples (p < 0.001).
      Interestingly, RIG-I staining identified 32% of DM patients without
      perifascicular atrophy (p = 0.007). RIG-I sensitivity was higher than
      perifascicular atrophy (p < 0.001). No differences in specificity between
      perifascicular atrophy and RIG-I staining were found (92% vs 88%). RIG-I staining
      was more reproducible than perifascicular atrophy (kappa coefficient 0.52 vs
      0.37). CONCLUSIONS: The perifascicular pattern of RIG-I expression supports the
      diagnosis of DM. Of importance for clinical and therapeutic studies, the
      inclusion of RIG-I in the routine pathological staining of samples in
      inflammatory myopathy will allow us to gather more homogeneous subgroups of
      patients in terms of immunopathogenesis.

PMID- 28738909
TI  - Quantifying associations of the dietary share of ultra-processed foods with
      overall diet quality in First Nations peoples in the Canadian provinces of
      British Columbia, Alberta, Manitoba and Ontario.
AB  - OBJECTIVE: To quantify associations of the dietary share of ultra-processed foods
      (UPF) with the overall diet quality of First Nations peoples. DESIGN: A cross
      sectional analysis of data from the First Nations Food, Nutrition and Environment
      Study, designed to contribute to knowledge gaps regarding the diet of First
      Nations peoples living on-reserve, south of the 60th parallel. A multistage
      sampling of communities was conducted. All foods from 24 h dietary recalls were
      categorized into NOVA categories and analyses were performed to evaluate the
      impact of UPF on diet quality. SETTING: Western and Central Canada. SUBJECTS:
      First Nations participants aged 19 years or older. RESULTS: The sample consisted
      of 3700 participants. UPF contributed 53.9 % of energy. Compared with the non-UPF
      fraction of the diet, the UPF fraction had 3.5 times less vitamin A, 2.4 times
      less K, 2.2 times less protein, 2.3 times more free sugars and 1.8 times more Na.
      As the contribution of UPF to energy increased so did the overall intakes of
      energy, carbohydrate, free sugar, saturated fat, Na, Ca and vitamin C, and Na:K;
      while protein, fibre, K, Fe and vitamin A decreased. Diets of individuals who ate
      traditional First Nations food (e.g. wild plants and game animals) on the day of
      the recall were lower in UPF. CONCLUSIONS: UPF were prevalent in First Nations
      diets. Efforts to curb UPF consumption and increase intake of traditional First
      Nations foods and other fresh or minimally processed foods would improve diet
      quality and health in First Nations peoples.

PMID- 28738910
TI  - On-line processing of English which-questions by children and adults: a visual
      world paradigm study.
AB  - Previous research has shown that children demonstrate similar sentence processing
      reflexes to those observed in adults, but they have difficulties revising an
      erroneous initial interpretation when they process garden-path sentences,
      passives, and wh-questions. We used the visual-world paradigm to examine
      children's use of syntactic and non-syntactic information to resolve syntactic
      ambiguity by extending our understanding of number features as a cue for
      interpretation to which-subject and which-object questions. We compared
      children's and adults' eye-movements to understand how this information shapes
      children's commitment to and revision of possible interpretations of these
      questions. The results showed that English-speaking adults and children both
      exhibit an initial preference to interpret an object-which question as a subject
      question. While adults quickly override this preference, children take
      significantly longer, showing an overall processing difficulty for object
      questions. Crucially, their recovery from an initially erroneous interpretation
      is speeded when disambiguating number agreement features are present.

PMID- 28738911
TI  - Sentinel visits in emergency department patients with diabetes mellitus as a
      warning sign for hyperglycemic emergencies.
AB  - OBJECTIVES: Patients with poorly controlled diabetes mellitus may have a sentinel
      emergency department (ED) visit for a precipitating condition prior to presenting
      for a hyperglycemic emergency, such as diabetic ketoacidosis (DKA) or
      hyperosmolar hyperglycemic state (HHS). This study's objective was to describe
      the epidemiology and outcomes of patients with a sentinel ED visit prior to their
      hyperglycemic emergency visit. METHODS: This was a 1-year health records review
      of patients>=18 years old presenting to one of four tertiary care EDs with a
      discharge diagnosis of hyperglycemia, DKA, or HHS. Trained research personnel
      collected data on patient characteristics, management, disposition, and
      determined whether patients came to the ED within the 14 days prior to their
      hyperglycemia visit. Descriptive statistics were used to summarize the data.
      RESULTS: Of 833 visits for hyperglycemia, 142 (17.0%; 95% CI: 14.5% to 19.6%) had
      a sentinel ED presentation within the preceding 14 days. Mean (SD) age was 50.5
      (19.0) years and 54.4% were male; 104 (73.2%) were discharged from this initial
      visit, and 98/104 (94.2%) were discharged either without their glucose checked or
      with an elevated blood glucose (>11.0 mmol/L). Of the sentinel visits, 93 (65.5%)
      were for hyperglycemia and 22 (15.5%) for infection. Upon returning to the ED,
      61/142 (43.0%) were admitted for severe hyperglycemia, DKA, or HHS. CONCLUSION:
      In this unique ED-based study, diabetic patients with a sentinel ED visit often
      returned and required subsequent admission for hyperglycemia. Clinicians should
      be vigilant in checking blood glucose and provide clear discharge instructions
      for follow-up and glucose management to prevent further hyperglycemic emergencies
      from occurring.

PMID- 28738912
TI  - Changes in dietary intake following a culturally adapted lifestyle intervention
      among Iraqi immigrants to Sweden at high risk of type 2 diabetes: a randomised
      trial.
AB  - OBJECTIVE: To investigate the effectiveness of a culturally adapted lifestyle
      intervention for changing dietary intake, particularly energy, fat and fibre
      intakes, in the intervention group (IG) compared with the control group (CG).
      DESIGN: Randomised controlled trial. SETTING: IG (n 50) and CG (n 46). The IG was
      offered seven group sessions, including one cooking class, over a period of 4
      months. The participants filled out 4 d food diaries at the start, mid and end of
      the study. SUBJECTS: Iraqi-born residents of Malmo, Sweden, at increased risk for
      developing diabetes. RESULTS: At baseline, participants' fat intake was high (40
      % of total energy intake (E%)). The predefined study goals of obtaining <30 E%
      from fat and >=15 g fibre/4184 kJ (1000 kcal) were met by very few individuals.
      In the IG v. the CG, the proportion of individuals obtaining <40 E% from fat
      (48.4 v. 34.6 %, P=0.65), <10 E% from saturated fat (32.3 v. 11.5 %, P=0.14) and
      >=10 g fibre/4184 kJ (45.2 v. 26.9 %, P=0.46) appeared to be higher at the last
      visit, although the differences were statistically non-significant. A trend
      towards decreased mean daily intakes of total energy (P=0.03), carbohydrate
      (P=0.06), sucrose (P=0.02) and fat (P=0.02) was observed within the IG.
      Differences in changes over time between the groups did not reach statistical
      significance. CONCLUSIONS: Although no significant differences were observed in
      the two groups, our data indicate that this culturally adapted programme has the
      potential to modify dietary intake in Middle Eastern immigrants. The high fat
      intake in this group should be addressed.

PMID- 28738913
TI  - Cumulative exposure to childhood adversity, and treated attention
      deficit/hyperactivity disorder: a cohort study of 543 650 adolescents and young
      adults in Sweden.
AB  - BACKGROUND: Though childhood adversity (CA) has been associated with the risk of
      attention deficit/hyperactivity disorder (ADHD), little is known about the effect
      of cumulative CAs and whether there are clusters of CAs that are more closely
      related with ADHD. METHODS: We used a Swedish cohort of 543 650 individuals born
      1987-1991. Register-based CAs included familial death, substantial parental
      substance abuse and psychiatric disorder, substantial parental criminality,
      parental separation, household public assistance recipiency, and residential
      instability. Individuals were followed from year 2006 when they were 15-19 years
      of age, for treated ADHD, defined as a registered ICD diagnosis and/or
      prescription of medications to treat ADHD. Logistic regression analysis was used
      to calculate odds ratios (OR) with 95% confidence intervals (CI). Latent Class
      Analyses (LCA) were used to identify clusters based on the different CAs.
      RESULTS: All CAs increased the odds of ADHD in late adolescence and early
      adulthood; ORs ranged from 1.6 (95% CI 1.5-1.8) for familial death to 2.7 (95% CI
      2.6-2.9) for household public assistance. We found a dose-response relationship
      between cumulative CA and ADHD; individuals with 4+ CAs had a markedly increased
      risk for ADHD (OR 5.5, 95% CI 5.0-6.0). LCA analyses revealed six distinct
      classes of CA associated with ADHD, of which 'exposure to most adversities'
      entailed highest risk. CONCLUSION: CA is a strong risk factor for ADHD,
      particularly when accumulated. Early and efficient detection of CA is of
      importance for interventions targeted to improve long-term mental health outcomes
      among disadvantaged children.

PMID- 28738914
TI  - Characterization of group B coxsackieviruses isolated from non-polio acute
      flaccid paralysis patients in Pakistan: vital assessment before polio
      eradication.
AB  - Pakistan is at the verge of polio eradication but isolation of non-polio
      enteroviruses (NPEVs) from acute flaccid paralysis (AFP) cases may result in
      serious or even fatal outcome. Many enteroviruses share similar symptoms and
      epidemiology as is the case with poliovirus and coxsackievirus (CV). The present
      study was designed to genetically characterize coxsackievirus B (CV-B) serotypes
      isolated from non-polio acute flaccid paralytic children, as well as to
      understand their probable role in paralysis. A total of 63 (20.1%) out of 313
      stool samples during 2013 were found positive for NPEVs in rhabdomyosarcoma
      cells. Only 24 (38.0%) NPEVs were typed as CV-B by microneutralization assay and
      were further characterized by sequencing of the viral protein 1 (VP1) gene.
      Molecular phylogenetic analyses classified the study strains into six
      coxsackievirus B serotypes (coxsackievirus B1 to B6) with their respective
      prototype strains with evidence of epidemiological linkage and distinct clusters.
      Moreover, four major differences were found within the amino acid sequences of BC
      loop in VP1 of CV-B strains. In conclusion, this study presented the molecular
      evolutionary genetic overview and distinct phylogenetic pattern of CV-B isolates
      from AFP cases in Pakistan, and explored the possible link between CV-B
      infections and AFP cases. Furthermore, our data reveal that these viruses might
      contribute to the incidence of paralysis in population and there is need of time
      to establish an enterovirus surveillance system for better understanding of
      epidemiological and virological characteristics of NPEV infections associated
      with AFP cases in the country.

PMID- 28738915
TI  - Laparoscopic Approach to Morgagni Hernias.

PMID- 28738916
TI  - The Effects of Distance and Time in Transfers for Emergency General Surgery.

PMID- 28738917
TI  - Intravenous Ketamine for Agitation in Critical Care.

PMID- 28738918
TI  - The Deleterious Effects of a Vaginal Pessary in a Patient with a History of
      Radiation Therapy to the Posterior Vaginal Wall.

PMID- 28738919
TI  - Laparoscopic Approach to Perforated Peptic Ulcers Trends Toward Quicker Recovery.

PMID- 28738920
TI  - Excision of a Presacral Ganglioneuroma in a Young Man.

PMID- 28738921
TI  - Acute Traumatic Subdural Hematoma among the Elderly: Reducing Readmission.

PMID- 28738922
TI  - Laparoscopic, Trans-Gastric Endoscopic Removal of Gastroesophageal Junction
      Gastrointestinal Stromal Tumors (GIST).

PMID- 28738924
TI  - Early Onset Massive Pulmonary Embolism after Penetrating Trauma in the Absence of
      Deep Vein Thrombosis.

PMID- 28738923
TI  - Laparoscopic Reduction of a Foramen of Winslow Internal Hernia Causing
      Transaminitis.

PMID- 28738925
TI  - Complicated Mammoplasty and Breast Salvage with Application of Extracellular
      Matrix.

PMID- 28738926
TI  - Innovative Surgical Technique Using Omentum to Isolate and Control an
      Enteroatmospheric Fistula.

PMID- 28738927
TI  - Heart Takes a Lickin' and Keeps on Tickin', Leave the Bullet.

PMID- 28738928
TI  - Performance of Southeastern Surgical Congress Examinees on the American Board of
      Surgery Examinations: An Educational Opportunity for Regional Collaboration.

PMID- 28738929
TI  - Iliac Artery Bullet Embolus after Isolated Thoracic Ballistic Injury.

PMID- 28738930
TI  - Pancreatic Lymphangioma: A Diagnostic and Treatment Dilemma.

PMID- 28738931
TI  - Management of Appendicitis with the Implementation of an Acute Care Surgery
      Service in a Community Teaching Hospital.

PMID- 28738932
TI  - Soft Tissue Malignancy Due to Long-Standing Foreign Bodies after Shotgun Blast.

PMID- 28738933
TI  - Repeatability of REBOA as an Unforeseen Tool.

PMID- 28738934
TI  - Neoadjuvant Talimogene Laherparepvec for the Treatment of Metastatic Melanoma.

PMID- 28738935
TI  - Pathologic and Prognostic Implications of Incidental versus Nonincidental
      Gallbladder Cancer: A 10-Institution Study from the United States Extrahepatic
      Biliary Malignancy Consortium.
AB  - Most gallbladder cancers (GBCs) are discovered incidentally after routine
      cholecystectomy. The influence of timing of diagnosis on disease stage,
      treatment, and prognosis is not known. Patients with GBC who underwent resection
      at 10 institutions from 2000 to 2015 were included. Patients diagnosed
      incidentally (IGBC) and nonincidentally (non-IGBC) were compared. Primary outcome
      was overall survival (OS). Of 445 patients with GBC, 266 (60%) were IGBC and 179
      (40%) were non-IGBC. Compared with IGBC, non-IGBC patients were more likely to
      have R2 resections (43% vs 19%; P < 0.001), advanced T-stage (T3/T4: 70% vs 40%;
      P < 0.001), high-grade tumors (50% vs 31%; P < 0.001), lymphovascular invasion
      (64% vs 45%; P = 0.01), and positive lymph nodes (60% vs 43%; P = 0.009). Receipt
      of adjuvant chemotherapy was similar between groups (49% vs 49%). Non-IGBC was
      associated with worse median OS compared with IGBC (17 vs 32 months; P < 0.001),
      which persisted among stage III patients (12 vs 29 months; P < 0.001), but not
      stages I, II, or IV. Despite accounting for other adverse pathologic factors
      (grade, T-stage, lymphovascular invasion, margin, lymph node), adjuvant
      chemotherapy was associated with improved OS only in stage III IGBC, but not in
      non-IGBC. Compared with incidental discovery, non-IGBC is associated with reduced
      OS, which is most evident in stage III disease. Despite being well matched for
      other adverse pathologic factors, adjuvant chemotherapy was associated with
      improved survival only in stage III patients with incidentally discovered cancer.
      This underscores the importance of timing of diagnosis in GBC and suggests that
      these two groups may represent a distinct biology of disease, and the same
      treatment paradigm may not be appropriate.

PMID- 28738936
TI  - Favorable Outcomes in Blunt Chest Injury with Noninvasive Bi-Level Positive
      Airway Pressure Ventilation.
AB  - Recent clinical research in patients with blunt chest injury has focused on the
      benefits of surgical fixation of rib fractures. Noninvasive ventilation (NIV) has
      been demonstrated to prevent the need for intubation and ventilation in
      posttraumatic respiratory failure. The preemptive use of NIV in patients with rib
      fractures has not been extensively studied. Our study evaluated the outcomes of
      patients with >=3 rib fractures and hospitalized for >= 4 days. Seventy-one
      patients treated with NIV were compared with 270 patients without NIV. NIV
      patients were older (65.8 vs 56.5 years) had more rib fractures (6.25 vs 5.32)
      and a higher body mass index (31 vs 27.8) than the comparison group, P < 0.05,
      but did not have an increased mortality or incidence of respiratory failure. NIV
      patients did have a statistically significant increase in length of stay compared
      to control (12.8 vs 8.8, P < 0.05). In the total sample, worse clinical outcomes
      were associated with older age, increased number of and bilateral rib fractures,
      higher Injury Severity Score, lower Glasgow Coma Scale, and higher body mass
      index. Outcomes in the most severely injured group of patients treated with NIV
      were comparable to other studies using surgical fixation of rib fractures and
      epidural pain control.

PMID- 28738937
TI  - Percutaneous Tracheostomy under Bronchoscopic Visualization Does Not Affect Short
      Term or Long-Term Complications.
AB  - Percutaneous tracheostomy is a safe and effective bedside procedure. Some
      advocate the use of bronchoscopy during the procedure to reduce the rate of
      complications. We evaluated our complication rate in trauma patients undergoing
      percutaneous tracheostomy with and without bronchoscopic guidance to ascertain if
      there was a difference in the rate of complications. A retrospective review of
      all tracheostomies performed in critically ill trauma patients was performed
      using the trauma registry from an urban, Level I Trauma Center. Bronchoscopy
      assistance was used based on surgeon preference. Standard statistical methodology
      was used to determine if there was a difference in complication rates for
      procedures performed with and without the bronchoscope. From January 2007, to
      April 2016, 649 patients underwent modified percuteaneous tracheostomy; 289 with
      the aid of a bronchoscope and 360 without. There were no statistically
      significant differences in any type of complication regardless of utilization of
      a bronchoscope. The addition of bronchoscopy provides several theoretical
      benefits when performing percutaneous tracheostomy. Our findings, however, do not
      demonstrate a statistically significant difference in complications between
      procedures performed with and without a bronchoscope. Use of the bronchoscope
      should, therefore, be left to the discretion of the performing physician.

PMID- 28738938
TI  - Minimally Invasive Incision and Drainage Technique in the Treatment of Simple
      Subcutaneous Abscess in Adults.
AB  - A minimally invasive (MI) approach using small incisions and vessel loops for
      drainage of simple perianal abscesses has been described in the pediatric
      population with decreased postoperative pain and comparable results to the
      traditional incision and drainage (I&D). The hypothesis was MI I&D will yield
      similar outcomes in adults. Patients who underwent I&D of perianal abscesses at
      an urban hospital from January 2008 to December 2015 were identified by Current
      Procedural Terminology code. Patients below 18 years of age, with inflammatory
      bowel diseases, or fistulae were excluded. Recurrences, readmissions, operative
      time, length of stay, complications, and costs were compared. There were 47
      traditional and 96 MI I&D with no significant differences in demographics,
      average body mass index, and abscess size. No significant differences were noted
      in recurrences, readmissions, length of stay, operative time, or costs (P >
      0.05). Postoperative complications occurred more frequently in the traditional
      group (P < 0.01) with a lower rate of follow-up (P < 0.05). MI I&D for simple
      anal abscesses in adults is associated with better compliance and fewer
      complications than the traditional approach. Although further studies are needed
      to determine if MI I&D confers superiority, this approach should be considered as
      first-line treatment for uncomplicated perirectal abscesses in adults.

PMID- 28738939
TI  - Can Tumor Biology Predict Occult Multifocal Disease in Breast Cancer Patients?
AB  - The SHAVE trial is a prospective trial in which 235 women with stage 0 to 3
      disease undergoing partial mastectomy were randomized intraoperatively to either
      have cavity shave's (CSMs) taken at the time of initial surgery or not. In this
      study, 9 of the 76 patients (11.8%) with initially negative margins randomized to
      the "shave" group had occult cancers found in the CSM. Seven of these patients
      had sufficient primary tumor tissue available for further analysis. These
      patients were age and stage matched in a 1:2 ratio to other patients in the trial
      who had no further disease found in their CSM. A tissue microarray was created,
      stained for E-cadherin, MUC1, and beta-catenin, and evaluated by two independent
      pathologists (blinded to outcome). There were no significant differences between
      cases and controls in terms of median invasive tumor size, ductal carcinoma in
      situ size, volume of initial resection, and volume of CSM. Further, no
      differences were noted between cases and controls for median (staining intensity
      * per cent of cells staining) for each marker. Hence, although nearly 12 per cent
      of breast cancer patients with negative margins will have occult disease, this
      could not be predicted by primary tumor markers in this study.

PMID- 28738940
TI  - Factors Affecting Choice of Treatment for Early-Stage Breast Cancer in West
      Virginia: A 10-Year Experience from a Rural Tertiary Care Center.
AB  - Recent literature shows changing trends in use of breast conservation surgery
      (BCS), mastectomy, and contralateral prophylactic mastectomy (CPM) in women with
      early-stage breast cancer (ESBC). We analyzed factors associated with selection
      of these treatment modalities in a rural West Virginia tertiary care hospital. We
      conducted a 10-year analysis of women treated for ESBC at our institution from
      the institutional cancer registry. Variables were compared between patients
      choosing BCS versus mastectomy. In women who chose mastectomy, predictors for
      choice of CPM were also examined. Variables with P < 0.05 on univariate analysis
      were entered into a multivariate logistic regression model to define independent
      predictors of treatment choice. The mastectomy rate increased from 18.0 per cent
      in 2006 to 40.2 per cent in 2013. On multivariate analysis, insurance status (P <
      0.001), comorbidities (P = 0.001), and surgeon graduation after 1987-a surrogate
      for surgeon age-(P = 0.010) predicted receipt of mastectomy. Of those receiving
      mastectomy, 106 (25.1%) elected CPM. CPM rates increased from 8.0 per cent in
      2006 to 45.0 per cent in 2013. Younger age at diagnosis (P < 0.001) and use of
      preoperative MRI (P = 0.012) independently predicted use of CPM versus unilateral
      mastectomy. Rates of mastectomy and CPM in ESBC have increased in West Virginia
      over time. Independent predictors of selecting mastectomy over BCS included
      insurance status, surgeon age, and associated comorbidities. Younger patients and
      patients receiving preoperative MRI were more likely to choose CPM. Awareness of
      these factors will aid in counseling women with ESBC and allow clinicians to
      address potential biases or disparities that may affect treatment choices.
      Further prospective study of these findings is warranted.

PMID- 28738941
TI  - Disparities in Rural Breast Cancer Care: Factors Affecting Choice of Breast
      Reconstruction in a West Virginia Tertiary Care Hospital.
AB  - The decision to pursue immediate postmastectomy breast reconstruction (IBR) is
      not uniform across all groups of women in the United States. We sought to
      investigate if the challenges of caring for a socioeconomically and
      geographically challenged rural population affected the incidence of IBR and to
      identify predictive factors of IBR in this population. Using our institution's
      cancer registry, we conducted a 10-year review of women with early-stage,
      unilateral breast cancer who received mastectomy. Demographics, insurance status,
      comorbidities, and surgeon graduation year were compared for patients receiving
      IBR versus no reconstruction. Variables with P < 0.05 on univariate analysis were
      included into a multivariate logistic regression model to determine independent
      predictors of IBR. From 2006 to 2015, 53/423 (12.5%) patients underwent IBR. On
      multivariate analysis, three factors independently predicted the decision to
      undergo IBR: age (P = 0.004), insurance type (P = 0.034), and use of
      contralateral prophylactic mastectomy (CPM, P < 0.001). Our data indicate that
      age, insurance type, and utilization of CPM influence the decision to pursue
      reconstruction. Additionally, the rate of IBR was found to be much lower in our
      West Virginia population than reported nationally, suggesting disparities in the
      care of women with early-stage, unilateral breast cancer in a rural population,
      even in a tertiary care environment.

PMID- 28738942
TI  - In the Modern Era of CT, Do Blunt Trauma Patients with Markers for Blunt Bowel or
      Mesenteric Injury Still Require Exploratory Laparotomy?
AB  - After blunt trauma, certain CT markers, such as free intraperitoneal air,
      strongly suggest bowel perforation, whereas other markers, including free
      intraperitoneal fluid without solid organ injury, may be merely suspicious for
      acute injury. The present study aims to delineate the safety of nonoperative
      management for markers of blunt bowel or mesenteric injury (BBMI) that are
      suspicious for significant bowel injury after blunt trauma. This was a
      retrospective review of adult blunt trauma patients with abdominopelvic CT scans
      on admission to a Level I trauma center between 2012 and 2014. Patients with CT
      evidence of acute BBMI without solid organ injury were included. The CT markers
      for BBMI included free intraperitoneal fluid, bowel hematoma, bowel wall
      thickening, mesenteric edema, hematoma and stranding. Two thousand blunt trauma
      cases were reviewed, and 94 patients (4.7%) met inclusion criteria. The average
      Injury Severity Score was 13.6 +/- 10.1 and the median hospital stay was four
      days. The most common finding was free fluid (74 patients, 78.7%). The majority
      of patients (92, 97.9%) remained asymptomatic or clinically improved without
      abdominal surgery. After a change in abdominal examination, two patients (2.1%)
      underwent laparotomy with bowel perforation found in only one patient. Thus, 93
      patients did not have a surgically significant injury, indicating that these
      markers demonstrate 1.1 per cent positive predictive value for bowel perforation.
      The presence of these markers after blunt trauma does not mandate laparotomy,
      though it should prompt thorough and continued vigilance toward the abdomen.

PMID- 28738943
TI  - Presenting Stage in Colon Cancer Is Associated with Insurance Status.
AB  - Colorectal cancer continues to be the third most common cause of cancer death in
      the United States. Access to health care is also a nationwide problem. The
      purpose of the current study is to see if insurance status is associated with
      stage of colon cancer at presentation. The tumor registry was queried for all
      patients with colon cancer from 2009 to 2014. Demographics, including insurance
      status was statistically analyzed to determine if an association existed between
      insurance status and stage of colon cancer at the time of presentation. There
      were 434 patients identified that underwent colonic resection during the study
      period; 224 were female and 210 were male. Of the 434 patients, 388 were insured
      and 46 were uninsured. When insurance status was compared with stage at diagnosis
      there was a statistically significant difference between the two groups. For
      patients that were uninsured, 13.01 per cent presented with stage I disease,
      15.22 per cent with stage II disease, 34.78 per cent with stage III disease, and
      36.96 with stage IV disease. For insured patients, 24.03 per cent present with
      stage I disease, 26.10 with stage II disease, 23.26 per cent with stage III
      disease, and 29.61 per cent with stage IV disease (P = 0.047). Access to health
      care continues to be a large problem and results in patients without insurance
      presenting with a high stage of disease.

PMID- 28738944
TI  - Predicting Postoperative Complications for Acute Care Surgery Patients Using the
      ACS NSQIP Surgical Risk Calculator.
AB  - The American College of Surgeons National Surgical Quality Improvement Program
      (ACS NSQIP) risk calculator has been used to assist surgeons in predicting the
      risk of postoperative complications. This study aims to determine if the risk
      calculator accurately predicts complications in acute care surgical patients
      undergoing laparotomy. A retrospective review was performed on all patients on
      the acute care surgery service at a tertiary hospital who underwent laparotomy
      between 2011 and 2012. The preoperative risk factors were used to calculate the
      estimated risks of postoperative complications in both the original ACS NSQIP
      calculator and updated calculator (June 2016). The predicted rate of
      complications was then compared with the actual rate of complications. Ninety
      five patients were included. Both risk calculators accurately predicted the risk
      of pneumonia, cardiac complications, urinary tract infections, venous
      thromboembolism, renal failure, unplanned returns to operating room, discharge to
      nursing facility, and mortality. Both calculators underestimated serious
      complications (26% vs 39%), overall complications (32.4% vs 45.3%), surgical site
      infections (9.3% vs 20%), and length of stay (9.7 days versus 13.1 days). When
      patients with prolonged hospitalization were excluded, the updated calculator
      accurately predicted length of stay. The ACS NSQIP risk calculator underestimates
      the overall risk of complications, surgical infections, and length of stay. The
      updated calculator accurately predicts length of stay for patients <30 days. The
      acute care surgical population represents a high-risk population with an
      increased rate of complications. This should be taken into account when using the
      risk calculator to predict postoperative risk in this population.

PMID- 28738945
TI  - Disparities in the Care of Differentiated Thyroid Cancer in the United States:
      Exploring the National Cancer Database.
AB  - Differentiated thyroid cancer (DTC) treatment is multifaceted, and may be
      influenced by socioeconomic factors. The goal of this study is to examine
      disparities in DTC treatment. DTC patients from 1998 to 2012 were identified
      using the National Cancer Database. DTC was identified in 262,041 patients. The
      mean age was 48.2. The majority of patients (52%) received care at Comprehensive
      Community Cancer Programs (CCCPs). Total thyroidectomy was less common at
      Community Cancer Programs (CCPs) [odds ratio (OR): 0.735; 95% confidence interval
      (CI): 0.707-0.764), and more common at academic centers (OR: 1.129; 95% CI: 1.102
      1.157) compared with CCCP. A central neck dissection was performed most often at
      academic center (20.6%) versus CCP (10.0%). Black patients were less likely to
      undergo central neck dissection compared with white patients (OR: 0.468; 95% CI:
      0.452-0.484). Patients more likely to receive radioactive iodine were white
      compared with black patients (hazard ratio: 0.833; 95% CI: 0.806-0.861),
      privately insured compared with uninsured patients (hazard ratio: 1.272; 95% CI:
      1.210-1.341), and patients treated at CCCP. Disparities exist in DTC treatment.
      Individuals at risk for under-treatment are black patients, uninsured patients,
      and those treated at CCP. As the Affordable Care Act changes access to health
      care, future studies will be needed to readdress disparities.

PMID- 28738946
TI  - Effect of Implementation of Intermittent Straight Catheter Protocol on Rate of
      Urinary Tract Infections in a Trauma Population.
AB  - Catheter-associated urinary tract infections (UTIs) are a significant negative
      outcome. There are previous studies showing advantages in removing Foleys early
      but no studies of the effect of using intermittent as opposed to Foley
      catheterization in a trauma population. This study evaluates the effectiveness of
      a straight catheter protocol implemented in February 2015. A retrospective chart
      review was performed on all patients admitted to the trauma service at a single
      institution who had a UTI one year before and one year after protocol
      implementation on February 18, 2015. The protocol involved removing Foley
      catheters early and using straight catheterization. Rates were compared with
      Fisher's exact test and continuous data were compared using student's t test.
      There were 1477 patients admitted to the trauma service in the control year and
      1707 in the study year. The control year had a total of 43 patients with a UTI,
      28 of these met inclusion criteria. The intervention year had a total of 35
      patients with a UTI and 17 met inclusion criteria. The rate of patients having a
      UTI went from 0.019 to 0.010 (p = 0.035). In females this rate went from 0.033 to
      0.009 (p = 0.007), whereas in males it went from 0.012 to 0.010 (p = 0.837). This
      study shows a statistically significant improvement in the rate of UTIs after
      implementing an intermittent catheterization protocol suggesting that this
      protocol could improve the rate of UTIs in other trauma centers. We use this for
      all trauma patients, and it is being looked at for use hospital-wide.

PMID- 28738947
TI  - Outpatient Total Thyroidectomy Is Safe for Moderate-Volume Surgeons.
AB  - Traditionally, total thyroidectomy (TT) was an inpatient procedure, but recent
      trends indicate that patients are often discharged on the day of surgery. This
      has been proven safe for high-volume surgeons but has not been studied for low
      (<10 TT per year) and moderate volume surgeons (<24 TT per year). Retrospective
      review was performed for 414 total thyroidectomies between 2005 and 2013.
      Emergency department visits and readmissions within 30 days of surgery were
      captured, but were considered the same for the purpose of this analysis. Patients
      were identified as outpatient if the day of discharge matched the day of surgery.
      The groups were compared based on demographic variables, comorbidities, postop
      calcium supplementation, and serum calcium. We found that moderate-volume
      surgeons were more likely to perform outpatient TT than low-volume surgeons
      (31.6% vs 6.0%, P < 0.001), but there was no correlation between length of stay
      and readmission (P = 0.688). Readmitted patients had lower postop serum calcium
      (8.3 mg/dL) than patients who were not readmitted (8.8 mg/dL, P = 0.006). Our
      data show that moderate-volume surgeons performing outpatient TT have an
      acceptable safety profile with respect to emergency department visits and
      hospital readmissions, and that same day discharge had no bearing on readmission.

PMID- 28738948
TI  - Socioeconomic Factors Associated with Readmission after Deceased Donor Renal
      Transplantation.
AB  - Early hospital readmissions after kidney transplantation pose a significant
      financial burden and hardship for patients and health-care institutions alike. We
      sought to identify the risk factors associated with increased likelihood of
      readmission after transplantation, and examined to determine whether patient
      socioeconomic demographics impacted the likelihood of perioperative readmissions.
      We evaluated all deceased donor renal transplants performed at our institution
      between August 2011 and December 2015. In a cohort of 325 transplant operations
      that met our inclusion criteria, 117 (36%) were readmitted to the hospital within
      90 days of discharge. In univariable analyses, length of stay and pretransplant
      disabled status were associated with increased likelihood of readmission within
      90 days of transplant. When placed into multivariable models, there was a
      suggestion association with length of stay and disability status. Kidney donor
      profile index, estimated posttransplant survival, employment, race, age, and
      payor status were not associated with readmission. In conclusion, the factors
      associated with posttransplant readmission are not necessarily influenced by
      socioeconomic factors in our study population. The data collected in this single
      center study indicate that the factors associated with increased rates of
      readmission are likely clinical in nature.

PMID- 28738949
TI  - Blood Transfusion and Survival for Resected Adrenocortical Carcinoma: A Study
      from the United States Adrenocortical Carcinoma Group.
AB  - Perioperative blood transfusion is associated with decreased survival in
      pancreatic, gastric, and liver cancer. The effect of transfusion in
      adrenocortical carcinoma (ACC) has not been studied. Patients with available
      transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at
      13 institutions comprising the United States Adrenocortical Carcinoma Group were
      included. Factors associated with blood transfusion were determined. Primary and
      secondary end points were recurrence-free survival (RFS) and overall survival
      (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of
      these, 57 patients (38.3%) received perioperative transfusions. Compared to
      nontransfused patients, transfused patients more commonly had stage 4 disease
      (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P < 0.001), inferior vena
      cava involvement (24.6% vs 5.4%, P = 0.002), additional organ resection (78.9% vs
      36.3%, P < 0.001), and major complications (29% vs 2%, P < 0.001). Transfusion
      was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs
      91.0 months, P < 0.001). On univariate Cox regression, transfusion, stage IV,
      hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS.
      On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95%
      confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7
      5.9, P < 0.001), and hormonal hypersecretion (HR = 2.6, 95% CI = 1.5-4.2, P <
      0.001) were associated with worse RFS. When applying this model to OS, similar
      associations were seen (transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4
      HR = 6.2, 95% CI = 3.1-12.4, P < 0.001; hormonal hypersecretion HR = 3.5, 95% CI
      = 1.9-6.4, P < 0.001). There was no difference in outcomes between patients who
      received 1 to 2 units versus >2 units of packed red blood cells in median RFS
      (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63).
      Perioperative transfusion is associated with earlier recurrence and decreased
      survival after curative-intent resection of ACC. Strategies and protocols to
      minimize blood transfusion should be developed and followed.

PMID- 28738951
TI  - Evaluation of Cardiopulmonary Complication Rates after Port Insertion: Is a
      Postoperative X-Ray Needed?
AB  - It is customary for a postoperative chest radiograph to be obtained after
      fluoroscopic guided port insertion to exclude acute complications. In this
      review, we provide a cost-benefit analysis by examination of acute postoperative
      complications detected by postoperative port insertion chest films at our
      institution. We conducted a retrospective chart review of complications
      associated with port insertion procedures performed over a 5-year period. Our
      study included only ultrasound-assisted internal jugular venous or landmark
      guided subclavian ports placed with the assistance of fluoroscopy. A total of 519
      port insertions were reviewed and there was noted to be a postoperative
      complication rate of 0.58 per cent. The operative note for each complication
      described a procedural abnormality that suggested a chest film would be of
      medical benefit. The total price of postoperative chest radiographs was $179,400.
      Performing chest X-ray films on asymptomatic patients after fluoroscopic guided
      placement of ports proved to be of no medical advantage to 516 out of 519
      patients. Given the extremely low complication rate and financial burden placed
      on the patient population, we propose discontinuing routine use of postoperative
      port placement chest radiographs as a way to alleviate unwarranted medical cost.

PMID- 28738950
TI  - A Decade Evaluation of a State Trauma System: Has Access to Inpatient Trauma Care
      at Designated Trauma Centers Improved?
AB  - Recently, the trauma center component of the Georgia trauma system was evaluated
      demonstrating a 10 per cent probability of increased survival for severely
      injured patients treated at designated trauma centers (DTCs) versus nontrauma
      centers. The purpose of this study was to determine the effectiveness of a state
      trauma system to provide access to inpatient trauma care at DTCs for its
      residents. We reviewed 371,786 patients from the state's discharge database and
      identified 255,657 treated at either a DTC or a nontrauma center between 2003 and
      2012. Injury severity was assigned using the International Classification Injury
      Severity Score method. Injury was categorized as mild, moderate, or severe.
      Patients were also categorized by age and injury type. Access improved over time
      in all severity levels, age groups, and injury types. Although elderly had the
      largest improvement in access, still only 70 per cent were treated at a DTC.
      During the study period, increases were noted for all age groups, injury severity
      levels, and types of injury. A closer examination of the injured elderly
      population is needed to determine the cause of lower utilization by this age
      group. Overall, the state's trauma system continues to mature by providing
      patients with increased access to treatment at DTCs.

PMID- 28738952
TI  - Medication Errors in Injured Patients.
AB  - Trauma patients are vulnerable to medication error given multiple handoffs
      throughout the hospital. The purpose of this study was to assess trends in
      medication errors in trauma patients and the role these errors play in patient
      outcomes. Injured adults admitted from 2009 to 2015 to a Level I trauma center
      were included. Medication errors were determined based on a nurse-driven,
      validated, and prospectively maintained database. Multivariable logistic
      regression modeling was used to control for differences between groups. Among
      15,635 injured adults admitted during the study period, 132 patients experienced
      243 errors. Patients who experienced errors had significantly worse injury
      severity, lower Glasgow Coma Scale scores and higher rates of hypotension on
      admission, and longer lengths of stay. Before adjustment, mortality was similar
      between groups but morbidity was higher in the medication error group. After risk
      adjustment, there were no significant differences in morbidity or mortality
      between the groups. Medication errors in trauma patients tend to occur in
      significantly injured patients with long hospital stays. Appropriate adjustment
      when studying the impact of medical errors on patient outcomes is important.

PMID- 28738953
TI  - Morbidity Associated with Diverting Loop Ileostomies: Weighing Diversion in
      Rectosigmoid Resection.
AB  - Anterior resection with primary anastomosis is the procedure of choice for
      patients with rectosigmoid cancers with good sphincter function. Surgeons may
      perform an associated diverting loop ileostomy (DLI) to minimize the likelihood
      and/or the severity of an anastomotic leak. To examine the morbidity of DLIs, we
      performed a review of a prospectively maintained database. Participants included
      all patients at the Massachusetts General Hospital who underwent anterior
      resection from January 2013 to July 2015 for rectosigmoid cancers and who
      subsequently underwent adjuvant chemotherapy. The primary outcome was time to
      start of adjuvant chemotherapy. Secondary outcomes included length of
      hospitalization, perioperative complications, and 60-day postoperative
      complications. Inclusion criteria were met in 57 patients and DLI was performed
      in 21 (37%). The DLI group had higher estimated blood loss (431.7 vs 192.1 mL, P
      = 0.03) and a longer operation time (3.7 vs 2.3 hours, P = 0.0007). The DLI group
      took over a week longer to start adjuvant chemotherapy than the non-DLI group
      (median time to chemo: 43 vs 34 days, P = 0.002). Postoperatively, DLI was
      associated with a longer hospitalization (6.7 vs 3.1 days, P = 0.0003), more
      perioperative complications (57.1% vs 13.9%, P = 0.0006), and more 60-day
      readmissions or emergency department visits (38.1% vs 5.6%, P = 0.002). Ostomies
      are associated with appreciable morbidity. In turn, they do not eliminate
      postoperative complications. Surgeons should closely consider ostomy morbidity in
      rectosigmoid resection and institute a proactive approach toward identification
      and prevention of complications.

PMID- 28738954
TI  - The Utility of the Alvarado Score in the Diagnosis of Acute Appendicitis in the
      Elderly.
AB  - Clinical scores determining the likelihood of acute appendicitis (AA), including
      the Alvarado score, were devised using a younger population, and their efficacy
      in predicting AA in elderly patients is not well documented. This study's purpose
      is to evaluate the utility of Alvarado scores in this population. A retrospective
      chart review of patients >65 years old presenting with pathologically diagnosed
      AA from 2000 to 2010 was performed. Ninety-six patients met inclusion criteria.
      The average age was 73.7 +/- 1.5 years and our cohort was 41.7 per cent male. The
      average Alvarado score was 6.9 +/- 0.33. The distribution of scores was 1 to 4 in
      3.7 per cent, 5 to 6 in 37.8 per cent, and 7 to 10 in 58.5 per cent of cases.
      There was a statistically significant increase in patients scoring 5 or 6 in our
      cohort versus the original Alvarado cohort (P < 0.01). Right lower quadrant
      tenderness (97.6%), left shift of neutrophils (91.5%), and leukocytosis (84.1%)
      were the most common symptoms on presentation. In conclusion, our data suggest
      that altering our interpretation of the Alvarado score to classify elderly
      patients presenting with a score of >=5 as high risk may lead to earlier
      diagnosis of AA. Physicians should have a higher clinical suspicion of AA in
      elderly patients presenting with right lower quadrant tenderness, left shift, or
      leukocytosis.

PMID- 28738955
TI  - Primary Site Predicts Grade for Gastroenteropancreatic Neuroendocrine Tumors.
AB  - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and abstruse
      neoplasms with increasing incidence and clinical relevance. The National Cancer
      Data Base was examined to identify GEP-NET cases from 2004 to 2013. In total,
      39,454 patients diagnosed with GEP-NET were identified. Median age was 61 years.
      Majority was female (50.13%), white (79.49%), and had low-grade neoplasms
      (84.39%). On univariate analysis, age, sex, race, primary site, tumor size, and
      regional lymph node involvement were associated with tumor grade (P < 0.0001). On
      multivariate analysis, older age [odds ratio (OR) = 9.57], gender (male, OR =
      1.29), and race continued to be associated with high-grade neoplasms. The primary
      site also remained a significant predictor of tumor grade. High-grade neoplasms
      were more likely to arise from the esophagus (OR = 317.75), hepatobiliary system
      (OR = 23.15), colorectum (OR = 14.37), ampulla of Vater (OR = 11.61), and stomach
      (OR = 7.84) compared with the appendix (OR = 5.41), pancreas (OR = 5.31), and
      small bowel (referent). The tumor grade for GEP-NETs is highly dependent on the
      primary site, suggesting different sites may be biologically distinct diseases. A
      personalized approach to GEP-NET treatment, tailored to the site of origin, is
      imperative.

PMID- 28738956
TI  - Upper Extremity Pulse Pressure Predicts Amputation-Free Survival after Lower
      Extremity Bypass.
AB  - Increased pulse pressure reflects pathologic arterial stiffening and predicts
      cardiovascular events and mortality. The effect of pulse pressure on outcomes in
      lower extremity bypass patients remains unknown. We thus investigated whether
      preoperative pulse pressure could predict amputation-free survival in patients
      undergoing lower extremity bypass for atherosclerotic occlusive disease. An
      institutional database identified 240 included patients undergoing lower
      extremity bypass from 2005 to 2014. Preoperative demographics, cardiovascular
      risk factors, operative factors, and systolic and diastolic blood pressures were
      recorded, and compared between patients with pulse pressures above and below 80
      mm Hg. Factors were analyzed in bi- and multivariable models to assess
      independent predictors of amputation-free survival. Kaplan-Meier analysis was
      performed to evaluate the temporal effect of pulse pressure >=80 mm Hg on
      amputation-free survival. Patients with a pulse pressure >=80 mm Hg were older,
      male, and had higher systolic and lower diastolic pressures. Patients with pulse
      pressure <80 mm Hg demonstrated a survival advantage on Kaplan-Meier analysis at
      six months (log-rank P = 0.003) and one year (P = 0.005) postoperatively. In
      multivariable analysis, independent risk factors for decreased amputation-free
      survival at six months included nonwhite race, tissue loss, infrapopliteal
      target, and preoperative pulse pressure >=80 mm Hg (hazard ratio 2.60; P = 0.02),
      while only tissue loss and pulse pressure >=80 mm Hg (hazard ratio 2.30, P =
      0.02) remained predictive at one year. Increased pulse pressure is independently
      associated with decreased amputation-free survival in patients undergoing lower
      extremity bypass. Further efforts to understand the relationship between
      increased arterial stiffness and poor outcomes in these patients are needed.

PMID- 28738957
TI  - Gaps in the Postoperative Conversation: A Comprehensive Review of Current
      Practices and the Unmet Needs of Surgeons, Families, and Waiting Room Personnel.
AB  - Perioperative communication between surgeons and caregivers is an important
      aspect of patient care, with postoperative conversations (POCs) being critical.
      Literature suggests current communication practices may be suboptimal.
      Identifying barriers and opportunities could improve patient and caregiver
      satisfaction and increase surgeon efficiency. This mixed method study included 1)
      prospective study of all patients undergoing a surgery at an academic medical
      center between September 2014 and March 2016 and 2) nominal groups of physicians,
      caregivers, and waiting room personnel (WRP). Nominal groups ranked standard of
      care themes needing intervention. Multivariate logistic regression estimated the
      association of surgeon and procedure characteristics with POC practices
      considering both location and contact method. Data on 15,820 operations showed
      that surgical specialty (P <= 0.0001), inpatient status (P <= 0.0001), planned
      discharge destination (P = 0.0003), patient race (P = 0.02), and caregiver
      relationship (P <= 0.0001) were all significantly associated with receiving a
      private POC. Nominal group results provided opportunities for improvement:
      regular updates (caregivers), locating the caregivers postoperation (surgeons),
      clear communication between caregivers and surgeons (WRP). This study examines
      the perioperative communication. Surgeons, caregivers, and WRP identified
      effective communication as a top intervention priority. Managing caregiver
      expectations, addressing concerns of WRP, and creating an efficient environment
      for surgeons appear to be critical components to communication.

PMID- 28738959
TI  - [Study on the Effect of Immunosuppressive Agent FK506 on Growth and Migration of
      Lung Cancer Cell].
AB  - BACKGROUND: FK506, also named tacrolimus, a new macrolide immunosuppressive
      agent, has been shown to possess anti-proliferation activities in some cancer
      cells. The aim of this study was to investigate the effect of FK506 on the cell
      proliferation and migration of lung cancer cell lines and its mechanism. METHODS:
      A549 and H1299 cell lines were cultured in vitro. The effect of FK506 on cell
      viability and DNA synthesis ability of A549 and H1299 were measured by CCK-8
      assay and EDU-labeling assay, respectively. Flow cytometry assay was used to
      detect the cell cycle. The in vitro migration of lung cancer cells was detected
      by Boyden chamber assay and wound-healing assay after the treatment of FK506. The
      expression of p27, RB1, CDK4, CDK6 and MMP9 were detected using Western blot.
      RESULTS: FK506 inhibited cell growth and induced cell cycle arrest in G0/G1 phase
      in A549 and H1299 cells in a dose- and time-dependent manner. Compared to the
      control groups, the migration of A549 and H1299 cells treated with FK506 were
      decreased obviously. Moreover, FK506 increased the expression of P27 and RB1, and
      reduced the expression of CDK4, CDK6 and MMP9. CONCLUSIONS: FK506 inhibit the
      cell growth and migration of lung cancer cells in vitro. The inhibitive effects
      may be associated with the up-regulation of p27 expression and inhibition CDK4,
      CDK6 and MMP9 expression.?.

PMID- 28738960
TI  - [MiR-218 Inhibits Migration and Invasion of Lung Cancer Cell ?by Regulating Robo1
      Expression].
AB  - BACKGROUND: To explore the function and the potential molecular mechanism of miR
      218 in lung cancer cell. METHODS: The expression of miR-218 mRNA was determined
      by real-time PCR in lung cancer tissues, adjacent tissues and lung cancer cells.
      Transwell assay was used to detect the migration and invasion of A549 cell after
      transfected with Anti-miR-218 or negative control and HC4006 cell after
      transfected with miR-218 mimics and miR-218 negative control. Targetscan and
      MiRanda were used to calculate the potential targets of miR-218 and Luciferase
      reporter assay was performed to identify that the Robo1 was one target genes of
      miR-218. Transwell assay was used to detect whether miR-218 regulated the
      invasion of lung cancer cell transfected with anti-miR-218 or negative control
      via Robo1. RESULTS: The expression of miR-218 in the lung cancer tissues was
      significantly lower than that in the adjacent tissues (P<0.05). Inhibition of miR
      218 improved the migration and invasion of A549 cell. Overexpression of miR-218
      suppressed the migration and invasion of HCC4006 cell. The co-transfection of
      anti-miR-218 or miR-218 mimics and the Robo1 3'UTR increased or reduced the
      luciferase activity of Robo1 compared with the control group (P<0.05). Inhibition
      of miR-218 and Robo1 recovered the invaded cells of A549. Overexpression of miR
      218 and inhibition of Robo1 reduced the number of the invased cells of HCC4006.
      These results suggested that miR-218 banded Robo1 directly and inhibited lung
      cancer cell invasion by targeting Robo1. CONCLUSIONS: MiR-218 inhibited the
      migration and invasion of lung cancer cells through regulating Robo1
      expression.?.

PMID- 28738958
TI  - [Expert Consensus for Thermal Ablation of Primary and Metastatic Lung Tumors
      ?(2017 Edition)].

PMID- 28738961
TI  - [Circular RNA CircHIPK3 Promotes NCI-H1299 and NCI-H2170 Cell Proliferation
      through miR-379 and its Target IGF1].
AB  - BACKGROUND: It has been proven that the circular RNA, possessing a stable
      covalently closed continuous loop, is a type of RNA molecule which is expressed
      widespread in mammals. The circular RNA circHIPK3 is abundantly expressed in
      hepatocellular carcinoma (HCC) and promotes tumourgenesis. However, a role for
      circHIPK3 has not been systematically examined in non-small cell lung cancer
      (NSCLC). In this study, we investigated whether circHIPK3 has an effect on cell
      proliferation in the NSCLC cell lines NCI-H1299 and NCI-H2170 and the underlying
      molecular mechanisms. METHODS: The expression of circHIPK3 was measured by real
      time PCR in NSCLC cell lines. Nuclear mass separation experiment was used to
      detect the location of circHIPK3 in cells. The gain and loss function experiments
      were used to examine the proliferation of NCI-H1299 and NCI-H2170 cells by Cell
      Counting Kit-8 (CCK-8) and the colony formation assays. Then, circHIPK3 was
      cloned into the downstream of the luciferase reporter gene which activity was
      detected to verify whether miR-379 could bind with circHIPK3 or IGF1 mRNA. The
      protein level of IGF1 was detected by Western blot and ELISA in circHIPK3
      overexpressed/knock-down NCI-H1299 and NCI-H2170 cells. RESULTS: CircHIPK3 was
      generally expressed in six kinds of NSCLC cells lines we detected, and the
      expression level was highest in H2170 and lowest in H1299. Overexpression of
      circHIPK3 obviously promoted NCI-H1299 cell proliferation and knock-down of
      circHIPK3 inhibited NCI-H2170 cell proliferation. In the luciferase assay, miR
      379 was observed to sequester circHIPK3 and IGF1 mRNA with potential binding
      sites. Furthermore, we found that the overexpression of circHIPK3 could increase
      the expression levels of IGF1 and knock-down reduced it. Moreover, up-regulation
      of miR-379 rescued the phenotype induced by overexpression of circHIPK3.
      CONCLUSIONS: CircHIPK3 could promote cell proliferation by a circHIPK3/miR-379
      pathway in NCI-H1299 and NCI-H2170 cells and might be a potential tumor biomarker
      for NSCLC.?.

PMID- 28738962
TI  - [Simplification and Validation of Leicester Cough Questionnaire in Mandarin
      Chinese].
AB  - BACKGROUND: Patients often have cough after lung surgery, and there is a lack of
      tools to specifically assess postoperative coughs. LCQ-MC (Leicester Cough
      Questionnaire in Mandarin-Chinese) was revised and validated to explore its value
      on clinical application. METHODS: A total of 250 patients undergone the lung
      operation of single medical team, from September 2015 to December 2016 in the
      Department ofThoracic Surgery, West China Hospital, Sichuan University, were
      investigated. Among them, 121 patients completed LCQ-MC and 129 patients
      completed simplified LCQ-MC, we verified the reliability and validity. RESULTS:
      The new questionnaire was not changed in terms of content layout and the scoring
      method of LCQ-MC, consisting of 12 items and three domains (physical,
      psychological and social). There was good content validity (S-CVI/UA=0.83).
      Concurrent validity was high when the simplified LCQ-MC was compared with daytime
      cough symptom score (r=-0.578, P<0.001). There was a moderate relationship with
      response to night-time cough symptom score (r=-0.358, P=-0.004) and SF36 total
      score (r=0.346, P=0.030), and weak relationship with the Hospital Anxiety and
      Depression Scale total score (r=-0.241, P=0.046). Cronbach's alpha coefficients
      of simplified LCQ-CM total and three domains varied between 0.79 and 0.89. One
      week apart test-retest reliability (n=30) was high (r=0.88-0.96). CONCLUSIONS:
      Simplified LCQ-MC has good reliability and validity that can be used for clinical
      applications.

PMID- 28738963
TI  - [Somatization Symptoms in Lung Cancer Patients and Correlative Analysis between
      Anxiety, Depression and Somatization Symptoms].
AB  - BACKGROUND: Lung cancer is a serious threat to human health and its morbidity and
      mortality in recent years has always been ranked first in the country. Lung
      cancer patients are often associated with anxiety, depression and other emotional
      problems, and anxiety, depression and other emotional problems will further lead
      to a series of somatic symptoms. At present, we lack the clinical understanding
      of somatization symptoms in patients with lung cancer and related clinical
      studies are not too much. This research is to study the features of clinical
      manifestation of lung cancer patients with somatization symptoms and correlative
      analysis between anxiety, depression and somatization symptoms in medical
      oncology department of general hospital. METHODS: Lung cancer patients who met
      somatization symptoms diagnostic standard were assessed with the self-constructed
      somatic symptoms investigation questionnaire, the Chinese version of the Patient
      Health Questionnaire-15 (PHQ-15) and anxiety and depression were recorded by the
      Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD). The detection
      rate of the anxiety, depression and the number of patients with different
      severity somatization symptoms were calculated, the relationship between the PHQ
      15 scores and anxiety and/or depression and the distribution of the different
      frequency somatization symptoms were analyzed. RESULTS: There were 43 patients
      with anxiety and/or depression in the 50 lung cancer patients with somatization
      symptoms. Prevalence rates of anxiety, depression and anxiety combined with
      depression were 10%, 10% and 66% respectively. The more severity the somatization
      symptoms are, the higher detection rates of anxiety combined with depression are.
      Significant positive correlations were observed between PHQ-15 scores, PHQ-15
      positive symptom numbers and HAMA scores (r=0.752, P<0.001; r=0.710, P<0.001),
      HAMD scores (r=0.648, P<0.001; r=0.618, P<0.001). The most common somatization
      symptoms were fatigue (96%), weakness (88%), sleep disturbance (84%), dizziness
      (82%), and pain in extremities (80%). There was no significant statistical
      difference in somatization symptoms between lung cancer patients with different
      gender (P>0.05). CONCLUSIONS: Symptoms of anxiety or depression were very common
      in lung cancer patients with somatization symptoms and there was a close
      relationship between anxiety, depression, and somatization symptoms. The most
      common symptoms of these patients were nonspecific generalized symptoms.?.

PMID- 28738964
TI  - [Clinical Research on Albumin-bound Paclitaxel-based Therapy in Advanced Lung
      Cancer].
AB  - BACKGROUND: Albumin-bound paclitaxel is a novel paclitaxel formulation formed by
      the combination of paclitaxel and human serum albumin (HSA) to improve the
      efficacy of paclitaxel and reduce its adverse reactions. The aim of this
      retrospective study is to observe the efficacy and safety of albumin-bound
      paclitaxel-based therapy in the treatment of lung cancer. METHODS: We have
      enrolled 50 patients with advanced or unresectable retreatment lung cancer who
      were admitted from November 2011 to December 2014. All patients were treated with
      albumin-bound paclitaxel-based therapy with a 21 day cycle (albumin-bound
      paclitaxel weekly by intravenous dose of 130 mg/m2 on day 1 and day 8). Efficacy
      was evaluated every two cycles according to Response Evaluation Criteria in Solid
      Tumors (RECIST) 1.1 and side effects were observed during each cycle. All
      patients were evaluated. RESULTS: The total objective response rate (ORR) of
      albumin-bound paclitaxel-based therapy was 20%, disease control rate (DCR) was
      68%. In the subgroup analysis, in squamous non-small-cell lung carcinoma groups,
      ORR and DCR were 26.7% and 80% respectively. Albumin-bound paclitaxel based
      chemotherapy combined anti-angiogenesis therapy had a promising overall response
      rate 36.4%. In the patients who had been previously treated with>=4 lines of
      chemotherapy DCR also reached 69.2%. The most common adverse reactions were
      hematologic toxicities and were all manageable, no hypersensitivity reactions or
      treatment-related grade 4 adverse events were reported. CONCLUSIONS: Weekly
      albumin-bound paclitaxel is effective and well tolerated in the treatment of
      advanced lung cancer including all histological subtypes. Albumin-bound
      paclitaxel was associated with superior efficacy in patients with squamous (SCC)
      histology and combined with anti-angiogenesis therapy. Albumin-bound paclitaxel
      shown to be an effective and safe regimen for elderly or previous heavily treated
      patients.

PMID- 28738965
TI  - [Effect of Adjuvant Chemotherapy on DFS for Patients with Stage I NSCLC].
AB  - BACKGROUND: Surgical resection is the best choice for early lung cancer, but the
      prognosis of early postoperative lung cancer is still very different, whether or
      not to apply adjuvant chemotherapy is controversial. This study examines the role
      of postoperative adjuvant chemotherapy in patients with stage I non-small cell
      lung cancer (NSCLC), particularly in high-risk groups. METHODS: Patients with
      pathologic stage Ia and stage Ib NSCLC who underwent complete (R0) resection
      between January 2009 and June 2013 were identified from Peking University
      People's Hospital and classified into two groups based on postoperative
      chemotherapy or not. Kaplan-Meier and Log-rank tests were used to compare disease
      free survival (DFS). Scored according to the number of risk factors, all patients
      were divided into three groups. Kaplan-Meier and Log-rank tests were used to
      compare DFS between them. The effect of postoperative chemotherapy on high-risk
      group was observed individually. RESULTS: A total of 465 patients including 284
      cases of stage Ia and 181 cases of stage Ib were enrolled in this study. For
      stage Ia there was no significant difference between the chemotherapy group and
      the control group in DFS (P=0.171), but the survival curve of the chemotherapy
      group was located below the control group. For stage Ib there was no significant
      difference between the two groups either (P=0.630). But there were significant
      differences on DFS between the three groups according to the number of risk
      factors (P<0.001). The more risk factors mean the worse DFS. However, independent
      analyses showed no significant effect of postoperative chemotherapy on DFS in the
      high-risk group patients (P=0.763). CONCLUSIONS: Postoperative chemotherapy does
      not have a positive effect on DFS in early stage non-small cell lung cancer, and
      chemotherapy may not be appropriate even for patients with multiple risk factors.

PMID- 28738966
TI  - [Lung Nodules Assessment--Analysis of Four Guidelines].
AB  - In the past 20 years, with the popularization of low-dose computed tomography
      (CT) screening, detection rate of lung nodules increased significantly. However,
      there are still many difficulties in making qualitative diagnosis for pulmonary
      nodules. The Lung nodule is a clinical common lung disease. The early onset for
      malignant nodules is quite hidden. Without early intervention, the course of
      disease can develop rapidly. For malignant nodules, the exacerbation can be very
      severe. Besides, the therapeutic effect can be unsatisfactory. If the lesion
      resection can be performed in early stage, lung cancer patients' prognosis can be
      improved significantly. At present, the guidelines of lung nodules' treatment are
      diverse, but these guidelines still can't reach a consensus until now. This
      article reviews the literature in National Comprehensive Cancer Network (NCCN)
      Clinical Practice Guidelines in Oncology for Non-Small Cell Lung Cancer (NSCLC),
      American College of Chest Physicians (ACCP) guidelines for the diagnosis and
      treatment of pulmonary nodules, Fleischner society lung cancer treatment strategy
      guide, and clinical practice consensus guidelines for Asia, which are pertaining
      to lung nodules diagnosis and treatment strategy and try to explain the
      similarities and differences between them.

PMID- 28738967
TI  - [Recent Advances in Association of Estrogen and Non-small Cell Lung Cancer].
AB  - Lung cancer, of which approximately 85% are non-small cell lung cancer (NSCLC),
      is one of the most prevalent cancers and the most leading cause of cancer
      mortality. Despite recent improvements in its treatment, the prognosis remains
      dismal. Previous studies have clearly proved that estrogen and estrogen receptors
      (ER) are involve in the pathogenesis and development of lung cancer. More and
      more evidences showed antiestrogen therapy may reverse the drug-resistance of
      platinum based chemotherapy in NSCLC patients and can enhance curative effect of
      epidermal growth factor receptor tyrosine kinase inhibitor. We will review recent
      progress in the function of estrogen in NSCLC and the treatment based on the ER
      signaling pathways for NSCLC in this article.

PMID- 28738968
TI  - Exploration of an allied health workforce redesign model: quantifying the work of
      allied health assistants in a community workforce.
AB  - The Victorian Assistant Workforce Model (VAWM) enables a systematic approach for
      the identification and quantification of work that can be delegated from allied
      health professionals (AHPs) to allied health assistants (AHAs). The aim of the
      present study was to explore the effect of implementation of VAWM in the
      community and ambulatory health care setting. Data captured using mixed methods
      from allied health professionals working across the participating health services
      enabled the measurement of opportunity for workforce redesign in the community
      and ambulatory allied health workforce. A total of 1112 AHPs and 135 AHAs from
      the 27 participating organisations took part in the present study. AHPs
      identified that 24% of their time was spent undertaking tasks that could safely
      be delegated to an appropriately qualified and supervised AHA. This equates to
      6837h that could be redirected to advanced and expanded AHP practice roles or
      expanded patient-centred service models. The VAWM demonstrates potential for more
      efficient implementation of assistant workforce roles across allied health. Data
      outputs from implementation of the VAWM are vital in informing strategic planning
      and sustainability of workforce change. A more efficient and effective workforce
      promotes service delivery by the right person, in the right place, at the right
      time.What is known about this topic? There are currently workforce shortages that
      are predicted to grow across the allied health workforce. Ensuring that skill mix
      is optimal is one way to address these shortages. Matching the right task to
      right worker will also enable improved job satisfaction for both allied health
      assistants and allied health professionals. Workforce redesign efforts are more
      effective when there is strong data to support the redesign.What does this paper
      add? This paper builds on a previous paper by Somerville et al. with a case study
      applying the workforce redesign model to a community and ambulatory health care
      setting. It provides evidence that this workforce redesign model enables data to
      be collected to identify the opportunity for redesign in the allied health
      workforce in this clinical setting.What are the implications for practitioners?
      There are career pathways and opportunity for growth in the allied health
      assistant workforce in the community and ambulatory health care setting. These
      opportunities will need to be coupled with the development of supervision and
      delegation skills in the allied health professional workforce to ensure that an
      integrated workforce is built to provide optimal clinical care in the community
      and ambulatory setting.

PMID- 28738969
TI  - Complex chromosomal neighborhood effects determine the adaptive potential of a
      gene under selection.
AB  - How the organization of genes on a chromosome shapes adaptation is essential for
      understanding evolutionary paths. Here, we investigate how adaptation to rapidly
      increasing levels of antibiotic depends on the chromosomal neighborhood of a drug
      resistance gene inserted at different positions of the Escherichia coli
      chromosome. Using a dual-fluorescence reporter that allows us to distinguish gene
      amplifications from other up-mutations, we track in real-time adaptive changes in
      expression of the drug-resistance gene. We find that the relative contribution of
      several mutation types differs systematically between loci due to properties of
      neighboring genes: essentiality, expression, orientation, termination, and
      presence of duplicates. These properties determine rate and fitness effects of
      gene amplification, deletions, and mutations compromising transcriptional
      termination. Thus, the adaptive potential of a gene under selection is a system
      property with a complex genetic basis that is specific for each chromosomal
      locus, and it can be inferred from detailed functional and genomic data.

PMID- 28738970
TI  - A predictive focus of gain modulation encodes target trajectories in insect
      vision.
AB  - When a human catches a ball, they estimate future target location based on the
      current trajectory. How animals, small and large, encode such predictive
      processes at the single neuron level is unknown. Here we describe small target
      selective neurons in predatory dragonflies that exhibit localized enhanced
      sensitivity for targets displaced to new locations just ahead of the prior path,
      with suppression elsewhere in the surround. This focused region of gain
      modulation is driven by predictive mechanisms, with the direction tuning shifting
      selectively to match the target's prior path. It involves a large local increase
      in contrast gain which spreads forward after a delay (e.g. an occlusion) and can
      even transfer between brain hemispheres, predicting trajectories moved towards
      the visual midline from the other eye. The tractable nature of dragonflies for
      physiological experiments makes this a useful model for studying the neuronal
      mechanisms underlying the brain's remarkable ability to anticipate moving
      stimuli.

PMID- 28738971
TI  - Rapamycin-ameliorated diabetic symptoms involved in increasing adiponectin
      expression in diabetic mice on a high-fat diet.
AB  - Recent studies showed that rapamycin improved diabetic complications. Here, we
      investigated the metabolic effects of rapamycin in type 2 diabetes model (T2DM)
      mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2
      mg/kg or vehicle only for 3 weeks and were maintained on a high-fat diet. The
      treated diabetic mice exhibited decreased body weight, blood glucose levels, and
      fat mass. FGF21 expression was suppressed in C57B/L6 mice, but adiponectin
      expression increased both in FGF21 KO and C57B/L6 mice. These results suggest
      that rapamycin may alleviate FGF21 resistance in mice on a high-fat diet. The
      reduction of adipose tissue mass of the diabetic mice may be due to the increased
      adiponectin.

PMID- 28738972
TI  - Clinicopathological evaluation of Marjolin ulcers over two decades.
AB  - Malignant changes arising on the previously traumatized or chronically inflamed
      skin are defined as Marjolin ulcers. They can develop on many different lesions
      but frequently they are detected on burn scars. Histopathologically, Marjolin
      ulcers are mostly diagnosed as squamous cell carcinoma and they need special
      attention when especially located on the lower extremities. In this study, 63
      patients treated for Marjolin ulcers between January 2000 and March 2015 were
      evaluated according to etiology, histological differentiation, primary tumor
      size, patient age and anatomical localization. Medical records of these patients
      were reviewed retrospectively. Mean age was 49.7 years. Average interval between
      the first injury and carcinoma development was 37.9 years. Most frequent
      etiologic factor was burn scars with 82.5%. Foot was the most frequently affected
      site with 28.6% and scalp was the second most frequent localization with 25.4%.
      Squamous cell carcinomas were detected in 88.9% of the patients and basal cell
      carcinomas were detected in 11.1% of the patients. For treatment, excision and
      grafting was performed for 48 patients (76.2%), excision and local flaps were
      used for 10 patients (15.9%) and excision and free flaps were used for five
      patients (7.9%). Regional lymph node dissection was performed for 12 patients
      (19%). Average follow up period was 46.5 months. Local recurrences were detected
      in nine patients (14.3%). In conclusion, Marjolin ulcers are aggressive tumors
      that require special care. In order to prevent life threatening sequelas of this
      entity, it is important to know basic aspects of clinical progress, prognostic
      factors and treatment modalities.

PMID- 28738973
TI  - Interactive effects between Lymphotoxin alpha +252 polymorphism and habits of
      substance use on risk of hepatocellular carcinoma.
AB  - : This case-control study aimed to assess the interactive effect between
      polymorphisms of lymphotoxin (LT) alpha +252 and habitual substance use on risk
      of hepatocellular carcinoma (HCC). We enrolled 150 pairs of sex- and age-matched
      HCC patients and unrelated healthy controls. LTalpha genotypes were detected with
      polymerase-chain reaction and restrictive fragment length polymorphisms.
      Information about habits of substance use was obtained through personal
      interview. Multivariate analysis indicated that LTalpha +252 G/G genotypes [odds
      ratio (OR) = 3.36], Hepatitis B surface antigen (OR = 16.68), antibodies to
      hepatitis C virus (OR = 34.88) and having at least two habits of substance use
      (OR = 2.50) were independent risk factors for HCC. There were additive
      interactions among LTalpha +252 G/G genotype, chronic viral hepatitis, and habit
      of each substance use. IN CONCLUSION: There are independent and additive
      interactions between LTalpha +252 G/G genotype, chronic viral hepatitis, and
      habits of substance use on risk of HCC.

PMID- 28738974
TI  - Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in
      the presence of predisposing systemic diseases for chronic kidney disease.
AB  - Aim of this study is to compare the effects of partial nephrectomy (PN) and
      radical nephrectomy (RN) for stage I renal cell carcinoma (RCC) on renal
      functions in patients with diabetes mellitus (DM) and/or hypertension (HT).
      Charts of patients who underwent surgery for stage I RCC in our department were
      retrospectively reviewed and patients with DM and/or HT were enrolled.
      Preoperative and postoperative estimated glomerular filtration rates (eGFR) were
      calculated according to the Modification of Diet in Renal Disease (MDRD)
      formulation for both RN and PN groups. Groups were compared for patient
      demographics, preoperative eGFR, postoperative eGFR and DeltaeGFR [(preoperative
      eGFR) - (postoperative eGFR)] which reflects the renal functional loss. There
      were 85 patients in the RN and 33 patients in the PN groups. Demographic data
      were similar but the patients in the PN group had smaller tumor size compared to
      RN group (32.2 +/- 11.8 mm vs 47.1 +/- 15.2 mm, p < 0.001). Preoperative eGFR did
      not differ between groups (75 +/- 28.4 mL/min/1.73 m2 vs 75.5 +/- 23.8
      mL/min/1.73 m2 in RN and PN groups, p = 0.929). However, there were significant
      differences between groups in terms of postoperative eGFR (57.5 +/- 21.7
      mL/min/1.73 m2 vs 74 +/- 27.5 mL/min/1.73 m2 in RN and PN groups, p < 0.001) and
      DeltaeGFR (17.5 +/- 4.2 mL/min/1.73 m2 vs 1.5 +/- 0.4 mL/min/1.73 m2 in RN and PN
      groups, p < 0.001). Our findings favor the use of PN over RN for stage I RCC
      whenever feasible in patients with predisposing systemic diseases for chronic
      kidney disease for better preservation of renal functions.

PMID- 28738975
TI  - The effect of cranioplasty in cognitive and functional improvement: Experience of
      post traumatic brain injury inpatient rehabilitation.
AB  - To investigate the effect of cranioplasty on rehabilitation of post-traumatic
      brain injury (TBI) patients, 37 patients with TBI were arranged by
      retrospectively assessment study. Those TBI patients receiving in-hospital
      rehabilitation in the Department of Rehabilitation in a medical center of South
      Taiwan from 2010 to 2015 were assigned into two groups: A and B. All patients
      entered the multidisciplinary holistic in-patient rehabilitation training for
      about 1 month. Patients in Group A received decompressive craniectomy (DC),
      patients in Group B received DC and cranioplasty. All assessments were arranged
      right on admission and before discharge. The functional activity evaluation
      included muscle power and Barthel index (BI), and cognitive function evaluation,
      including the Rancho Los Amigo Scale, Mini Mental State Examination (MMSE),
      Community Mental State Examination (CMSE), and the Luria-Nebraska
      Neuropsychological Battery-Screening Test Short Form (LNNBS). The results showed
      that there were synergetic effects of cranioplasty on post-TBI patients with
      rehabilitation training, especially in the BI score, and cognitive improvement in
      CMSE and LNNBS.

PMID- 28738976
TI  - Proposal of a diagnostic algorithm for intraductal ultrasonography to distinguish
      between benign and malignant biliary strictures.
AB  - To reexamine the recognizability of intraductal ultrasonography (IDUS) findings
      from an imaging database and propose a novel algorithm for clinical application.
      IDUS images of 102 patients who had undergone IDUS examinations for indeterminate
      causes of common bile duct dilation were independently reviewed by two
      endoscopists. The strength of the inter-rater agreement between the endoscopists
      was analyzed using Cohen's kappa (kappa). An algorithm was implemented by
      arranging the IDUS characteristics according to their recognizability. The
      proposed algorithm was evaluated by examining the inter-rater agreement and
      diagnostic accuracy before and after the use of the algorithm. The strength of
      the inter-rater agreement was good for common bile duct stones with or without
      acoustic shadowing; intraluminal tumors; or bile duct wall thicknesses of more
      than or equal to 9 mm (kappa > 0.8); followed by intraluminal hypoechoic nodules
      without common bile duct stone characteristics (kappa = 0.771); and finally
      eccentric wall thickening, outer layer disruption, irregular mucosa, and
      destructed mural layers (kappa: 0.595-0.419). Our algorithm improved the strength
      of inter-rater agreement with a diagnostic accuracy of 81.4%. We proposed an
      algorithm according to the recognizability of IDUS characteristics, and it can be
      used by endoscopists to evaluate such characteristics and determine the cause of
      biliary obstruction.

PMID- 28738977
TI  - Glutathione peroxidase 3 gene polymorphisms and the risk of sudden sensorineural
      hearing loss.
AB  - The glutathione peroxidase 3 gene (GPX3) is reported to be a risk factor for
      arterial ischaemic stroke and cerebral venous thrombosis. GPX3 may be one of the
      aetiologies of sudden sensorineural hearing loss (SSNHL), which might be
      attributed to the genetic effect of GPX3 by influence reactive oxygen species
      (ROS). Unbalanced ROS have been associated with susceptibility to SSNHL.
      Therefore, we conducted a case-control study with 416 SSNHL cases and 255
      controls. Five single nucleotide polymorphisms (SNPs) were selected. The
      genotypes were determined using TaqMan genotyping assays. Each SNP was tested
      using the Hardy-Weinberg equilibrium (HWE), and the genetic effects were
      evaluated using three inheritance models. All five SNPs were in HWE. As the
      result, the AG genotype of rs3805435 had an adjusted odds ratio (OR) of 0.54 (95%
      confidence interval = 0.37-0.79, p = 0.001) compared with the AA genotype in the
      SSNHL cases. The GG and AG genotypes of the SNP rs3805435 were associated with
      SSNHL under the dominant model (p = 0.002, OR = 0.58). In conclusion, these
      results suggest that GPX3 polymorphisms influence susceptibility to SSNHL in
      southern Taiwan.

PMID- 28738978
TI  - Osteolytic lesions resulting from opportunistic infections.

PMID- 28738979
TI  - Angiosarcoma of kidney with calcification: A rare case report.

PMID- 28738980
TI  - Corrigendum to: "Parsing recursive sentences with a connectionist model including
      a neural stack and synaptic gating" [J. Theor. Biol. 271(2011)100-105].

PMID- 28738981
TI  - Copy-Forward in Electronic Health Records: Lipstick on a Pig.

PMID- 28738982
TI  - Safe Practice Recommendations for the Use of Copy-Forward with Nursing Flow
      Sheets in Hospital Settings.
AB  - BACKGROUND: In early 2016 the Partnership for Health IT Patient Safety released
      safe practice recommendations for the use of copy-paste for electronic health
      record (EHR) documentation. These recommendations do not directly address nurses'
      use of copy-forward to document patient assessments in flow sheet software in
      hospital settings. Similar to clinicians' use of copy-paste and copy-forward with
      progress notes, concerns exist about patient safety issues from the use of
      potential inaccurate or outdated information to achieve increased efficiency of
      documentation. METHODS: A multiple-methods approach-which included a literature
      review, litigation search, stakeholder analysis, and consensus opinion from
      experts from multiple disciplines-was employed. RESULTS: Four recommendations
      correspond closely with copy-paste guidance for EHR documentation from the
      Partnership: (1) Provide a mechanism to make copied-forward content easily
      identifiable, (2) Ensure that the provenance of copied-forward content is readily
      available, (3) Ensure adequate staff training and education regarding the
      appropriate and safe use of copy-forward in flow sheet software, if available,
      and (4) Ensure that copy-forward practices are regularly monitored, measured, and
      assessed. A fifth additional recommendation is made to improve the efficiency of
      data entry mechanisms, which may reduce patient safety risk. Emerging promising
      areas for innovation are to optimize interface usability and flow sheet content,
      use templates, use digital photographs, and eliminate work-flow steps with better
      methods for authentication and data entry. CONCLUSIONS: A thoughtful and measured
      approach to safe use of copy-forward in flow sheets by nurses in hospital
      settings is expected to result in improvements in efficiency of documentation,
      work flow, and accuracy of information.

PMID- 28738983
TI  - Power, Knowledge, and Transfusions: The Need to Refocus on Patient Blood
      Management.

PMID- 28738984
TI  - Transfusing Wisely: Clinical Decision Support Improves Blood Transfusion
      Practices.
AB  - BACKGROUND: The cost and risks of red blood cell (RBC) transfusions, along with
      evidence of overuse, suggest that improving transfusion practices is a key
      opportunity for health systems to improve both the quality and value of patient
      care. Previous work, which included a BestPractice Advisory (BPA), was adapted in
      a quality improvement project designed to reduce both exposure to unnecessary
      blood products and costs. METHODS: A prospective, pre-post study was conducted at
      an academic medical center with a diverse patient population. All noninfant
      inpatients without gastrointestinal bleeding who were not within 12 hours of
      surgical procedures were included. The interventions were education, a BPA, and
      other enhancements to the computerized provider order entry system. RESULTS: The
      percentage of multiunit (>= 2 units) RBC transfusions decreased from 59.9% to
      41.7% during the intervention period and to 19.7% postintervention (p < 0.0001).
      The percentage of inpatient RBC transfusion units administered for hemoglobin
      (Hb) >= 7 g/dL declined from 72.3% to 57.8% during the intervention period and to
      38.0% for the postintervention period (p < 0.0001). The overall rate of inpatient
      RBC transfusion (units administered per 1,000 patient-days without exclusions)
      decreased from 89.8 to 78.1 during the intervention period and to 72.7 during the
      postintervention period (p <0.0001). The estimated annual cost savings was
      $1,050,750. CONCLUSION: The interventions reduced multiunit transfusions (by
      67.1%) and transfusions for Hb >= 7 g/dL (by 47.4%). The improvement in the
      overall transfusion rate (19.0%) was less marked, limited by better baseline
      performance relative to other centers.

PMID- 28738985
TI  - Intraoperative Handoffs Among Anesthesia Providers Increase the Incidence of
      Documentation Errors for Controlled Drugs.
AB  - BACKGROUND: When electronic anesthesia records are compared to pharmacy
      transactions, discrepancies in total doses of controlled drugs are commonly found
      (~16% of cases), potentially affecting patient safety and placing hospitals at
      risk for regulatory action. Errors (~5%) persisted even with near real-time drug
      reconciliation feedback to providers. A study was conducted to test the
      hypothesis of greater risks of discrepancy for longer-duration cases and for
      intraoperative handoff involving a permanent handoff of care. METHODS: Anesthesia
      drug documentation and pharmacy transaction data were examined for all
      anesthetics between May 2014 and September 2015 at an academic medical center,
      and discrepancies between the two systems were determined. Nine logistic
      regression models were constructed to evaluate the influence of covariates (for
      example, case duration, general anesthesia vs. sedation, and handoff involving a
      permanent transfer of patient care) on the presence of a discrepancy. Linear
      regression was also performed between case duration decile and the logit
      (discrepancy rate), stratified by anesthesia type and handoff. RESULTS: For all
      models, handoffs were associated with higher discrepancy rates (p <10-6; odds >=
      1.38). There was a progressive increase in discrepancy rates as a function of the
      case duration. CONCLUSIONS: Handoffs involving a permanent transfer of patient
      care during cases increase the risk of controlled drug discrepancies. Staff
      scheduling and assignment decisions to decrease the chance of a handoff occurring
      should help mitigate this. In addition, future studies should examine ways to
      improve the handoff process related to controlled drugs (for example, a formal,
      structured processes in the anesthesia information management system).

PMID- 28738986
TI  - Pilot Testing Fall TIPS (Tailoring Interventions for Patient Safety): a Patient
      Centered Fall Prevention Toolkit.
AB  - BACKGROUND: Patient falls during an acute hospitalization cause injury, reduced
      mobility, and increased costs. The laminated paper Fall TIPS Toolkit (Fall TIPS)
      provides clinical decision support at the bedside by linking each patient's fall
      risk assessment with evidence-based interventions. Strategies were needed to
      integrate this evidence into clinical practice. METHODS: The Institute for
      Healthcare Improvement's Framework for Spread is the conceptual model for pilot
      implementation of Fall TIPS at Brigham and Women's Hospital (BWH; Boston) and
      Montefiore Medical Center (MMC; Bronx, New York). The key to translating the
      evidence into practice was engaging stakeholders by leveraging existing shared
      governance structures, identifying unit champions, holding training sessions for
      all staff, and implementing auditing to assess and provide feedback on protocol
      adherence and patient outcomes. RESULTS: BWH unit compliance with using Fall TIPS
      averaged 82%, the mean fall rate decreased from 3.28 to 2.80 falls per 1,000
      patient-days from January through June 2015 versus 2016, and the mean fall with
      injury rate for these periods decreased from 1.00 to 0.54 per 1,000 patient-days.
      At MMC, compliance averaged 91%, but the mean fall rate increased marginally from
      3.04 to 3.10, while the mean fall with injury rate decreased from 0.47 to 0.31
      per 1,000 patient-days. Patient knowledge survey results show improvement in
      knowledge of the risks for falls and the ways to prevent falls. CONCLUSION:
      Engaging hospital and clinical leadership is critical in translating evidence
      based care into clinical practice. Barriers to adoption of the protocol have been
      addressed and detailed to provide guidance for spread to other institutions.

PMID- 28738987
TI  - Evaluation of Sensor Technology to Detect Fall Risk and Prevent Falls in Acute
      Care.
AB  - BACKGROUND: Sensor technology that dynamically identifies hospitalized patients'
      fall risk and detects and alerts nurses of high-risk patients' early exits out of
      bed has potential for reducing fall rates and preventing patient harm. During
      Phase 1 (August 2014-January 2015) of a previously reported performance
      improvement project, an innovative depth sensor was evaluated on two inpatient
      medical units to study fall characteristics. In Phase 2 (April 2015-January
      2016), a combined depth and bed sensor system designed to assign patient fall
      probability, detect patient bed exits, and subsequently prevent falls was
      evaluated. METHODS: Fall detection depth sensors remained in place on two
      medicine units; bed sensors used to detect patient bed exits were added on only
      one of the medicine units. Fall rates and fall with injury rates were evaluated
      on both units. RESULTS: During Phase 2, the designated evaluation unit had 14
      falls, for a fall rate of 2.22 per 1,000 patient-days-a 54.1% reduction compared
      with the Phase 1 fall rate. The difference in rates from Phase 1 to Phase 2 was
      statistically significant (z = 2.20; p = 0.0297). The comparison medicine unit
      had 30 falls-a fall rate of 4.69 per 1,000 patient-days, representing a 57.9%
      increase as compared with Phase 1. CONCLUSION: A fall detection sensor system
      affords a level of surveillance that standard fall alert systems do not have.
      Fall prevention remains a complex issue, but sensor technology is a viable fall
      prevention option.

PMID- 28738988
TI  - Use of Cascading A3s to Drive Systemwide Improvement.

PMID- 28738990
TI  - XLIII National Congress of the Sociedad Espanola de Enfermeria Intensiva y
      Unidades Coronarias.

PMID- 28738991
TI  - Prophylactic Vaccines, Successes, Errors, and Complications.

PMID- 28738989
TI  - Membrane Curvature and Lipid Composition Synergize To Regulate N-Ras Anchor
      Recruitment.
AB  - Proteins anchored to membranes through covalently linked fatty acids and/or
      isoprenoid groups play crucial roles in all forms of life. Sorting and
      trafficking of lipidated proteins has traditionally been discussed in the context
      of partitioning to membrane domains of different lipid composition. We recently
      showed that membrane shape/curvature can in itself mediate the recruitment of
      lipidated proteins. However, exactly how membrane curvature and composition
      synergize remains largely unexplored. Here we investigated how three critical
      structural parameters of lipids, namely acyl chain saturation, headgroup size,
      and acyl chain length, modulate the capacity of membrane curvature to recruit
      lipidated proteins. As a model system we used the lipidated minimal membrane
      anchor of the GTPase, N-Ras (tN-Ras). Our data revealed complex synergistic
      effects, whereby tN-Ras binding was higher on planar DOPC than POPC membranes,
      but inversely higher on curved POPC than DOPC membranes. This variation in the
      binding to both planar and curved membranes leads to a net increase in the
      recruitment by membrane curvature of tN-Ras when reducing the acyl chain
      saturation state. Additionally, we found increased recruitment by membrane
      curvature of tN-Ras when substituting PC for PE, and when decreasing acyl chain
      length from 14 to 12 carbons (DMPC versus DLPC). However, these variations in
      recruitment ability had different origins, with the headgroup size primarily
      influencing tN-Ras binding to planar membranes whereas the change in acyl chain
      length primarily affected binding to curved membranes. Molecular field theory
      calculations recapitulated these findings and revealed lateral pressure as an
      underlying biophysical mechanism dictating how curvature and composition
      synergize to modulate recruitment of lipidated proteins. Our findings suggest
      that the different compositions of cellular compartments could modulate the
      potency of membrane curvature to recruit lipidated proteins and thereby
      synergistically regulate the trafficking and sorting of lipidated proteins.

PMID- 28738992
TI  - The dream of surgery without complications: A great step, much to do.

PMID- 28739011
TI  - Corrigendum to "Physical and Functional Interactions between ELL2 and RB in the
      Suppression of Prostate Cancer Cell Proliferation, Migration, and Invasion"
      [Neoplasia 19 (2017) 207-215].

PMID- 28739012
TI  - Corrigendum to "Synergistic Activity of N-Hydroxy-7-(2-Naphthylthio) Heptanomide
      and Sorafenib against Cancer Stem Cells, Anaplastic Thyroid Cancer" [Neoplasia 19
      (2017) 145-153].

PMID- 28739013
TI  - Influence of Access Cavity Design on Root Canal Detection, Instrumentation
      Efficacy, and Fracture Resistance Assessed in Maxillary Molars.
AB  - INTRODUCTION: The aim of this study was to assess the influence of contracted
      endodontic cavities (CECs) on root canal detection, instrumentation efficacy, and
      fracture resistance assessed in maxillary molars. Traditional endodontic cavities
      (TECs) were used as a reference for comparison. METHODS: Thirty extracted intact
      maxillary first molars were scanned with micro-computed tomographic imaging at a
      resolution of 21 MUm, assigned to the CEC or TEC group (n = 15/group), and
      accessed accordingly. Root canal detection was performed in 3 stages: (1) no
      magnification, (2) under an operating microscope (OM), and (3) under an OM and
      ultrasonic troughing. After root canal preparation with Reciproc instruments (VDW
      GmbH, Munich, Germany), the specimens were scanned again. The noninstrumented
      canal area, hard tissue debris accumulation, canal transportation, and centering
      ratio were analyzed. After root canal filling and cavity restoration, the sample
      was submitted to the fracture resistance test. Data were analyzed using the
      Fisher exact, Shapiro-Wilk, and t tests (alpha = 0.05). RESULTS: It was possible
      to locate more root canals in the TEC group in stages 1 and 2 (P < .05), whereas
      no differences were observed after stage 3 (P > .05). The percentage of
      noninstrumented canal areas did not differ significantly between the CEC (25.8%
      +/- 9.7%) and TEC (27.4% +/- 8.5%) groups. No significant differences were
      observed in the percentage of accumulated hard tissue debris after preparation
      (CEC: 0.9% +/- 0.6% and TEC: 1.3% +/- 1.4%). Canal transportation was
      significantly higher for the CEC group in the palatal canal at 7 mm from the
      apical end (P < .05). Canal preparation was more centralized in the palatal canal
      of the TEC group at 5 and 7 mm from the apical end (P < .05) and in the
      distobuccal canal of the CEC group at 5 mm from the apical end (P < .05). There
      was no difference regarding fracture resistance among the CEC (996.30 +/- 490.78
      N) and TEC (937.55 +/- 347.25 N) groups (P > .05). CONCLUSIONS: The current
      results did not show benefits associated with CECs. This access modality in
      maxillary molars resulted in less root canal detection when no ultrasonic
      troughing associated to an OM was used and did not increase fracture resistance.

PMID- 28739014
TI  - Optimal Radiotherapy for Unfavorable-risk Prostate Cancer.

PMID- 28739015
TI  - Randomised Controlled Trials Remain the Key to Progress in Localised Prostate
      Cancer.

PMID- 28739016
TI  - Response to "Best Practices for Chiropractic Care for Older Adults: A Systematic
      Review and Consensus Update".

PMID- 28739017
TI  - Response to Letter to Editor: "Best Practices for Chiropractic Care for Older
      Adults: A Consensus Update".

PMID- 28739018
TI  - Prediction Effects of Personal, Psychosocial, and Occupational Risk Factors on
      Low Back Pain Severity Using Artificial Neural Networks Approach in Industrial
      Workers.
AB  - OBJECTIVES: This study aimed to provide an empirical model of predicting low back
      pain (LBP) by considering the occupational, personal, and psychological risk
      factor interactions in workers population employed in industrial units using an
      artificial neural networks approach. METHODS: A total of 92 workers with LBP as
      the case group and 68 healthy workers as a control group were selected in various
      industrial units with similar occupational conditions. The demographic
      information and personal, occupational, and psychosocial factors of the
      participants were collected via interview, related questionnaires, consultation
      with occupational medicine, and also the Rapid Entire Body Assessment worksheet
      and National Aeronautics and Space Administration Task Load Index software. Then,
      16 risk factors for LBP were used as input variables to develop the prediction
      model. Networks with various multilayered structures were developed using MATLAB.
      RESULTS: The developed neural networks with 1 hidden layer and 26 neurons had the
      least error of classification in both training and testing phases. The mean of
      classification accuracy of the developed neural networks for the testing and
      training phase data were about 88% and 96%, respectively. In addition, the mean
      of classification accuracy of both training and testing data was 92%, indicating
      much better results compared with other methods. CONCLUSION: It appears that the
      prediction model using the neural network approach is more accurate compared with
      other applied methods. Because occupational LBP is usually untreatable, the
      results of prediction may be suitable for developing preventive strategies and
      corrective interventions.

PMID- 28739019
TI  - The Effect of 2 Different Exercise Programs on Pain Intensity and Muscle
      Dimensions in Patients With Chronic Low Back Pain: A Randomized Controlled Trial.
AB  - OBJECTIVES: The purpose of this study was to compare the effect of 2 exercise
      programs combined with electrotherapy on pain intensity and lumbar stabilizer
      muscles dimensions in patients with nonspecific chronic low back pain. METHODS: A
      randomized controlled clinical trial was performed with 41 patients with chronic
      LBP. Participants were randomly allocated into 2 groups: an experimental group (n
      = 20) received stabilization exercises plus electrotherapy, and a control group
      (n = 21) received routine exercises plus electrotherapy. Pain intensity, using a
      visual analog scale, and muscle dimensions of both right and left transverse
      abdominis and lumbar multifidus muscles, using rehabilitative ultrasonography,
      were assessed before and immediately after 4 weeks of intervention. RESULTS:
      Significant improvement was identified after interventions on pain intensity and
      muscle size measurements in both groups (P < .01 in all instances). The only
      exception was the right-side lumbar multifidus cross-sectional area of the
      control group, which was not statistically significant (P = .081). No significant
      differences were found between the 2 exercise groups on pain intensity and muscle
      dimensions (P > .05 in all instances). CONCLUSIONS: The results of this study
      suggest that a combination of electrotherapy with either routine or stabilization
      exercise programs may improve pain intensity and muscle dimensions in patients
      with nonspecific chronic low back pain.

PMID- 28739020
TI  - A Multimodal Approach for Myofascial Pain Syndrome: A Prospective Study.
AB  - OBJECTIVE: The purpose of this study was to analyze pain intensity in patients
      with myofascial pain syndrome (MPS) following a multimodal rehabilitation
      protocol. METHODS: A prospective study was carried out following the Template for
      Intervention Description and Replication criteria. Patients were recruited from
      the rehabilitation unit of a university hospital in Spain between 2009 and 2013.
      Patients were included if they had a medical diagnosis of MPS in any of the
      following regions: cervicobrachial (n = 102), lumbosacral (n = 30), elbow (n =
      14), ankle and foot (n = 10), and temporomandibular jaw (n = 1). The multimodal
      rehabilitation protocol included myofascial trigger point dry needling, spray and
      stretching, Kinesio taping, eccentric exercise, and patient education. The
      protocol was applied for 4 weeks (5 sessions) for the active and/or latent
      myofascial trigger points in each body region. Pain intensity was measured by
      using the visual analog scale (VAS) immediately before beginning of the study and
      1 week after completion of the protocol. RESULTS: The study sample comprised 150
      patients (mean +/- standard deviation age, 51.5 +/- 1.19 years). Statistically
      significant differences were obtained for reduction in pain intensity (4 +/-
      2.03; P = .002). Clinically relevant reductions (VAS >=30 mm; P < .001) were
      obtained in 78.7% of the interventions. Four treatment sessions reduced the VAS
      score by 10 mm in 83.55% of the sample. There were no statistically significant
      differences (P = .064) for reduction in pain intensity in the different body
      regions. CONCLUSIONS: A multimodal rehabilitation protocol showed clinically
      relevant differences in the reduction in pain intensity in different body regions
      in patients with MPS.

PMID- 28739021
TI  - Single and multiple food allergies in infants with proctocolitis.
AB  - BACKGROUND: Food protein-induced allergic proctocolitis is a frequent cause of
      rectal bleeding in infants. Characteristics of infants with multiple food
      allergies have not been defined. OBJECTIVE: This study aimed to identify
      characteristics of infants with proctocolitis and compare infants with single and
      multiple food allergies. METHODS: A total of 132 infants with proctocolitis were
      evaluated retrospectively. All of the infants were diagnosed by a paediatric
      allergist and/or a paediatric gastroenterologist according to guidelines.
      Clinical features of the infants, as well as results of a complete blood count,
      skin prick test, specific immunoglobulin E, and stool examinations or colonoscopy
      were recorded. RESULTS: Cow's milk (97.7%) was the most common allergen, followed
      by egg (22%). Forty-five (34.1%) infants had allergies to more than one food.
      Infants with multiple food allergies had a higher eosinophil count (613+/-631.2
      vs. 375+/-291.9) and a higher frequency of positive specific IgE and/or positive
      skin prick test results than that of patients with a single food allergy. Most of
      the patients whose symptoms persisted after two years of age had multiple food
      allergies. CONCLUSIONS: There is no difference in clinical presentations between
      infants with single and multiple food allergies. However, infants with multiple
      food allergies have a high blood total eosinophil count and are more likely to
      have a positive skin prick test and/or positive specific IgE results.

PMID- 28739023
TI  - Suture bridge transosseous equivalent repair is stronger than transosseous tied
      braided-tape.
AB  - BACKGROUND: This study biomechanically compares two methods of supraspinatus
      repair: single row transosseous braided-tape (BT) and suture bridge transosseous
      equivalent (SBTE) with 2 medial anchors and 2 lateral anchors. The purpose is to
      test the hypothesis that BT provides superior or equal biomechanical strength
      compared to SBTE. METHODS: Nine pairs of frozen cadaveric shoulders were selected
      and both repair techniques were tested on each pair, using a biomechanical
      testing unit to measure cyclic loading and ultimate load to failure. Moreover,
      tendon displacement was measured using the percentage of footprint exposed during
      the cyclic loading phase. RESULTS: Mean specimen age was 71 years (6 males, 3
      females), and mean volumetric bone mineral density was 134 mg/cm3. BT mean
      ultimate load was 266 +/- 81 Newton (N) compared to 398 +/- 69 N for SBTE and
      this difference of 131 N was statistically significant p = 0.025. There was a
      strong positive correlation between bone mineral density and SBTE construct
      ultimate load. The difference between the percentage of footprint exposed after
      cyclic loading of the two repairs was statistically significant with the
      exception of the 10-80 N load (p < 0.05). The failure mode was suture cutout
      through the tendon in 88% (7/8) of specimens for both techniques. CONCLUSION:
      SBTE repair with bone anchors provides superior biomechanical strength compared
      to BT repair in terms of ultimate load and cyclic loading. The tendon-suture
      junction is the weakness of both methods. These models simulate a complete tear
      with total loss of contact with rotator interval and infraspinatus. Future
      studies could focus on a more isolated physiologic supraspinatus tear pattern.
      LEVEL OF EVIDENCE: Basic science study (Level II).

PMID- 28739022
TI  - Component-resolved diagnosis in hymenoptera allergy.
AB  - Component-resolved diagnosis based on the use of well-defined, properly
      characterised and purified natural and recombinant allergens constitutes a new
      approach in the diagnosis of venom allergy. Prospective readers may benefit from
      an up-to-date review on the allergens. The best characterised venom is that of
      Apis mellifera, whose main allergens are phospholipase A2 (Api m1), hyaluronidase
      (Api m2) and melittin (Api m4). Additionally, in recent years, new allergens of
      Vespula vulgaris have been identified and include phospholipase A1 (Ves v1),
      hyaluronidase (Ves v2) and antigen 5 (Ves v5). Polistes species are becoming an
      increasing cause of allergy in Europe, although only few allergens have been
      identified in this venom. In this review, we evaluate the current knowledge about
      molecular diagnosis in hymenoptera venom allergy.

PMID- 28739024
TI  - The toxicity effects of ammonia on anaerobic digestion of organic fraction of
      municipal solid waste.
AB  - In this research the inhibitory effects of ammonia on the AD of synthetic OFMSW
      were examined under different total ammonia nitrogen (TAN) concentrations of
      2,500, 5,000, 7,500, and 10,000mg/L and at pH levels of 7.5, 8.0 and 8.5 using a
      factorial experimental design and statistical analysis. Reduction in Cumulative
      Biogas Production (CBP) at a TAN concentration of 2,500mg/L was close to 10% for
      all 3 pH levels. For a TAN concentration of 10,000mg/L the percent reduction in
      CBP was over 80% for all 3 pH levels showing significant inhibition due to
      ammonia with neglible influence due to change in pH. However, pH played a more
      significant role for TAN concentrations between the above two levels, as at a TAN
      concentartion of 7,500mg/L, the percent reduction in CBP increased from 42.2% at
      a pH of 7.5 to 76.5% at a pH of 8.5. Regression analysis was used to estimate CBP
      and % reduction (%R) in CBP using a quadratic equation with pH and TAN as
      independant variables (R2=0.95 and 0.94). Methane produciton per g of COD removed
      was obsereved to vary from 264mL CH4/g CODd for control reactors at pH 7.5 down
      to 1mL CH4/g CODd for the reactor at pH of 8.5 which contained 10,000mg/L TAN.
      Results of gradual ammonia loading also showed that mesophilic bacteria could be
      adapted to a TAN concentration of up to 5,000mg/L at pH 7.5 through gradual TAN
      loading. At 10,000mg/L TAN CBP in reactors with gradual TAN loading was more than
      1.9-3 times the CBP in reactors with abrupt TAN addition.

PMID- 28739025
TI  - Soldering mask laser removal from printed circuit boards aiming copper recycling.
AB  - Management of waste of electric and electronic equipment (WEEE) is a key issue
      for modern societies; furthermore, it contains valuable materials that can be
      recycled, especially in printed circuit boards (PCB), which have approximately
      one-third of their weight in copper. In this study we demonstrated the use of
      laser to strip the covering soldering mask on PCB's, thus exposing the copper
      underneath so that extraction techniques may take place. Using a Q-Switched
      Nd:YAG laser operating at 1064nm and 532nm we tested the procedure under
      different energy conditions. The laser stripping of the soldering mask was
      achieved with satisfactory results by irradiation with 225mJ at 1064nm. However,
      when using similar parameters at 532nm the process of the coating ejection was
      not promoted properly, leading to a faulty detachment. Infrared laser PCB
      stripping presents itself to be technically viable and environmental friendly,
      since it uses no chemicals inputs, offering one more option to WEEE treatment and
      recycling.

PMID- 28739026
TI  - The influence of joint technologies on ELV recyclability.
AB  - Stricter vehicle emission legislation has led to the increasing use of
      lightweight materials and multi-material concepts to reduce the vehicle mass. To
      account for the complexity of multi-material vehicle designs, the choice of
      joining techniques used is becoming more diverse. Moreover, the different
      material combinations, and their respective joining methods play an important
      role in determining the potential of full material separation in a closed-loop
      system. This paper evaluates the types of joining technologies used in the
      automotive industry, and identifies those that hinder the sorting of ELV
      materials. The study is based on an industrial shredding trial of car doors.
      Observations from the case study showed that steel screws and bolts are
      increasingly used to combine different material types and are less likely to be
      perfectly liberated during the shredding process. The characteristics of joints
      that lead to impurities and valuable material losses, such as joint strength,
      material type, size, diameter, location, and protrusion level, can influence the
      material liberation in the current sorting practices and thus, lead to ELV waste
      minimisation. Additionally, the liberation of joints is also affected by the
      density and thickness of materials being joined. Correlation analyses are carried
      out to further support the influence of mechanical screws and bolts on material
      separation efficiencies. The observations are representative of the initial
      phases of current global ELV sorting practices.

PMID- 28739027
TI  - Undiagnosed attention deficit/hyperactivity disorder (ADHD) among unionized
      drivers in Ghana: Public health and policy implications.
AB  - Road traffic accidents (RTA) are among the leading causes of mortality in sub
      Saharan Africa. Many males that drop out of school in Ghana, a population at risk
      for attention-deficit hyperactivity disorder (ADHD), find employment by joining
      driver's unions. Moreover, the vehicles of Ghanaian unionized drivers are over
      represented in fatal road accidents. Untreated ADHD has been linked with higher
      rates of RTAs. The objectives of this cross-sectional analysis is to determine
      the following among unionized drivers in Ghana: 1) the prevalence of ADHD, and 2)
      the association between self-reported ADHD risk and driving behavior. Data comes
      from participants' responses (200 unionized drivers and 171 community controls)
      to a 6-item ADHD Self - Report Scale (ASRS), the Driving Behavior Survey (DBS),
      and a culturally adapted version of the Jerome Driving Questionnaire (JDQ-GH).
      The self-reported prevalence of ADHD was 17.6% for the unionized drivers and 7.8%
      for the control group (chi2=7.7, df=1, p=0.006). Also, ADHD drivers endorsed that
      they were more likely to pay bribes to police and having worse driving behaviors
      across among both unionized drivers and controls. Study findings suggest that
      increased awareness of ADHD and possible screening of drivers for ADHD with
      subsequent evaluation and treatment may result in prevention of vehicle
      accidents.

PMID- 28739028
TI  - Incident Learning Systems for Radiation Oncology: Development and Value at the
      Local, National and International Level.
AB  - AIMS: To discuss the background for incident reporting and learning systems, as
      well as the infrastructure and operational aspects to run them. MATERIALS AND
      METHODS: Information from peer-reviewed literature, online resources and the
      authors' experience synthesised into a concise understanding of the topic.
      RESULTS: Incident learning systems can be local, national or international, each
      having the same basic goals but facilitating different audiences and
      environments. A key component of any reporting and learning system is timely and
      effective analysis of near-misses and incidents as well as feedback to the users
      of the system. It is important for staff to know that reports are acknowledged,
      analysed and acted upon. There is a need to comply with current European
      legislation and other national systems, which can be addressed together with the
      steps required for comprehensive management of an incident. CONCLUSION: Reporting
      and learning from incidents and near-misses is a key component of quality and
      safety in radiotherapy. A major benefit of the national or international systems
      is the potential for a larger database of incidents, supporting wider analysis
      and comparison, and sharing of knowledge across a larger community.

PMID- 28739030
TI  - Immune modulatory microRNAs as a novel mechanism to revert immune escape of
      tumors.
AB  - Tumors have developed different strategies to escape immune recognition. This
      could be due to altered expression of classical and non-classical human leukocyte
      antigens (HLA), co-inhibitory or co-stimulatory molecules as well as components
      of the interferon signaling pathway. Furthermore, changes in the tumor
      microenvironment negatively interfere with anti-tumor immune responses and the
      frequency and activity of immune effector cells and professional antigen
      presenting cells (APC), while the number of immune suppressive cells is
      increased. Recently, microRNAs (miRNA) identified known as important players in
      the posttranscriptional regulation of gene expression have been demonstrated to
      be differentially expressed in tumors of distinct origin and present in
      nanovesicles secreted by tumors. They not only exhibit tumor suppressive and
      oncogenic potential, but also immune modulatory functions. This review focusses
      on the role of miRNA in posttranscriptional control of immune modulatory
      molecules in tumors and in exosomes, which might represent prognostic biomarkers
      and novel therapeutic targets.

PMID- 28739029
TI  - IL-9 and Th9 cells in health and diseases-From tolerance to immunopathology.
AB  - CD4+ T cells have the capacity to differentiate into various T helper (Th) cell
      subsets after activation, and by acquiring distinct cytokine profiles and
      effector functions, they regulate the nature as well as the outcomes of immune
      responses. Th9 cells are a relatively new member in the Th cell family. The
      signature cytokine for Th9 cells is IL-9, a cytokine in the IL-2Rgammac-chain
      family. Over the past few years, there has been an explosion of knowledge on the
      roles of Th9 cells in immunity and immunopathology, but the exact mechanisms in
      the control of Th9 cells remain poorly defined. This apparent paradox presents
      both challenges and opportunities. Here we review recent advances in our
      understanding of the fundamental biology of IL-9 and Th9 cells, highlighting the
      challenges and unanswered questions in the field. We also discuss potential
      opportunities in targeting Th9 cells for therapeutic purposes in the clinic.

PMID- 28739031
TI  - Comparison of Outcomes of Pericardiocentesis Versus Surgical Pericardial Window
      in Patients Requiring Drainage of Pericardial Effusions.
AB  - Comparative outcomes of patients undergoing pericardiocentesis or pericardial
      window are limited. Development of pericardial effusion after cardiac surgery is
      common but no data exist to guide best management. Procedural billing codes and
      Cleveland Clinic surgical registries were used to identify 1,281 patients who
      underwent either pericardiocentesis or surgical pericardial window between
      January 2000 and December 2012. The 656 patients undergoing an intervention for a
      pericardial effusion secondary to cardiac surgery were also compared. Propensity
      scoring was used to identify well-matched patients in each group. In the overall
      cohort, in-hospital mortality was similar between the group undergoing
      pericardiocentesis and surgical drainage (5.3% vs 4.4%, p = 0.49). Similar
      outcomes were found in the propensity-matched group (4.9% vs 6.1%, p = 0.55). Re
      accumulation was more common after pericardiocentesis (24% vs 10%, p <0.0001) and
      remained in the matched cohorts (23% vs 9%, p <0.0001). The secondary outcome of
      hemodynamic instability after the procedure was more common in the pericardial
      window group in both the unmatched (5.2% vs 2.9%, p = 0.036) and matched cohorts
      (6.1% vs 2.0%, p = 0.022). In the subgroup of patients with a pericardial
      effusion secondary to cardiac surgery, there was a lower mortality after
      pericardiocentesis in the unmatched group (1.5% vs 4.6%, p = 0.024); however,
      after adjustment, this difference in mortality was no longer present (2.6% vs
      4.5%, p = 0.36). In conclusion, both pericardiocentesis and surgical pericardial
      window are safe and effective treatment strategies for the patient with a
      pericardial effusion. In our study there were no significant differences in
      mortality in patients undergoing either procedure. Observed differences in
      outcomes with regard to recurrence rates, hemodynamic instability, and in those
      with postcardiac surgery effusions may help to guide the clinician in management
      of the patient requiring therapeutic or diagnostic drainage of a pericardial
      effusion.

PMID- 28739032
TI  - Comparison and Validation of Recommended QT Interval Correction Formulas for
      Predicting Cardiac Arrhythmias in Patients With Advanced Heart Failure and
      Cardiac Resynchronization Devices.
AB  - QT interval prolongation is an important marker for the development of cardiac
      arrhythmias (CAs). Optimal methods to estimate QT/QTc intervals in patients with
      ventricular pacing (VP) and its correlation with CA have not been widely
      investigated. We aimed to validate the currently available formulas for QT
      determination during VP and to compare their abilities in predicting the
      occurrence of CA (atrial fibrillation [AF] and malignant ventricular arrhythmias
      [VAs] in patients with advanced heart failure and cardiac resynchronization
      therapy). Consecutive patients with advanced heart failure who underwent cardiac
      resynchronization therapy implantation between August 2001 and April 2015 were
      included in a retrospective study. Four proposed formulas for QT correction in VP
      rhythms were evaluated. One hundred eighty patients were enrolled. During 44
      months of follow-up, 43 patients (37.7%) developed AF and 16 patients (8.9%)
      developed VA. There was no correlation between corrected QT increments and AF
      risk with any of the formulas for paced rhythms. Regarding VA, higher corrected
      QT values measured with Massachusetts' formula (QTcM) were found to have a higher
      risk of event (p = 0.036) (Beta = 1.012 [1.001 to 1.023]). Each 1 ms increase in
      QTc increased the probability of experiencing VA by 120/00. QTcM >444 was found
      to be a strong predictor of VA. In conclusion, there are significant differences
      in mean QTc interval measured by the currently advised formulas. QTc interval was
      not associated with AF in any of the formulas. Only the QTcM formula showed a
      significant stepwise increase in the risk of experiencing malignant VA.

PMID- 28739034
TI  - Evaluation of Resting Cardiac Power Output as a Prognostic Factor in Patients
      with Advanced Heart Failure.
AB  - If the heart is represented by a hydraulic pump, cardiac power represents the
      hydraulic function of the heart. Cardiac pump function is frequently determined
      through left ventricular ejection fraction using imaging. This study aims to
      validate resting cardiac power output (CPO) as a predictive biomarker in patients
      with advanced heart failure (HF). One hundred and seventy-two patients with HF
      severe enough to warrant cardiac transplantation were retrospectively reviewed at
      a single tertiary care institution between September 2010 and July 2013. Patients
      were initially evaluated with simultaneous right-sided and left-sided cardiac
      catheter-based hemodynamic measurements, followed by longitudinal follow-up
      (median of 52 months) for adverse events (cardiac mortality, cardiac
      transplantation, or ventricular assist device placement). Median resting CPO was
      0.54 W (long rank chi-square = 33.6; p < 0.0001). Decreased resting CPO (<0.54 W)
      predicted increased risk for adverse outcomes. Fifty cardiac deaths, 10 cardiac
      transplants, and 12 ventricular assist device placements were documented. The
      prognostic relevance of resting CPO remained significant after adjustment for
      age, gender, left ventricular ejection fraction, mean arterial pressure,
      pulmonary vascular resistance, right atrial pressure, and estimated glomerular
      filtration rate (HR, 3.53; 95% confidence interval, 1.66 to 6.77; p = 0.0007). In
      conclusion, lower resting CPO supplies independent prediction of adverse
      outcomes. Thus, it could be effectively used for risk stratification in patients
      with advanced HF.

PMID- 28739033
TI  - Soluble ST2 for Risk Stratification and the Prediction of Mortality in Patients
      Undergoing Transcatheter Aortic Valve Implantation.
AB  - This study aimed to assess the prognostic value of soluble ST2 (sST2) for risk
      stratification in patients undergoing transcatheter aortic valve implantation
      (TAVI). In 461 patients undergoing TAVI, sST2 was determined at baseline and
      categorized into quartiles. An optimum cutoff of 29 ng/ml was calculated. Primary
      end point was 1-year all-cause mortality. Results were validated in an
      independent cohort. Patients with sST2 >29 ng/ml had an increased 30-day (9.7% vs
      4.6%, p = 0.043) and 1-year mortality (38.1% vs 21.8%, p = 0.001). In accordance,
      patients with N-terminal pro-brain natriuretic peptide (NT-proBNP) >8145 pg/ml
      revealed a comparable 30-day mortality (7.9% vs 4.7%, p = 0.189) and 1-year
      mortality (39.5% vs 21.0%, p <0.001). In univariate regression analysis, sST2 and
      NT-proBNP were associated with increased mortality risk. In multivariate
      regression analysis, independent predictors of mortality were logistic EuroSCORE,
      chronic renal failure, left ventricular ejection fraction, and sST2. In receiver
      operating characteristic curve analysis, sST2 did not provide incremental
      prognostic information beyond that obtained from surgical risk scores such as the
      STS-PROM or NT-proBNP. Similar findings could be achieved in an independent
      validation cohort. In conclusion, sST2 is independently associated with adverse
      outcome after TAVI but was not superior to NT-proBNP or surgical risk scores for
      the prediction of postprocedural outcomes.

PMID- 28739035
TI  - Relationship Between Birth Weight and the Double Product in Childhood,
      Adolescence, and Adulthood (from the Bogalusa Heart Study).
AB  - Low birth weight is associated with cardiovascular disease and its risk factors,
      including heart rate and blood pressure. Therefore, we examined the hypothesis
      that birth weight is related to blood pressure-heart rate product (double
      product, DP), an index of oxygen consumption and workload of the heart, at
      different ages. Heart rate at rest, blood pressure at rest, and birth weight data
      were available in 2,340 children (4 to 11 years), 1,621 adolescents (12 to 19
      years), and 2,315 adults (20 to 52 years) from the Bogalusa Heart Study (total n
      = 6,276). After adjustment for age, sex, race, and body mass index, gestational
      age-adjusted birth weight was inversely associated with DP, with per 100-g
      decrease in birth weight associated with an increase of 12.8, 22.9, and 23.2
      beats/min * mmHg in DP in children (p = 0.016), adolescents (p = 0.0007), and
      adults (p = 0.0006), respectively. An amplifying trend of the association with
      age was observed in the total sample (p = 0.002). In conclusion, birth weight is
      associated with increased DP beginning in childhood, which may partly mediate the
      association between low birth weight and increased cardiovascular risk later in
      life.

PMID- 28739036
TI  - Meta-Analysis of the Effect of Obstructive Sleep Apnea on Cardiovascular Events
      After Percutaneous Coronary Intervention.
AB  - Increasing evidence proved that obstructive sleep apnea (OSA) is associated with
      a variety of diseases, especially cardiovascular diseases. This study
      systematically reviewed the existing publications to assess the influence of OSA
      on cardiovascular survival among patients who underwent percutaneous coronary
      intervention. Eleven eligible publications, including 3,008 participants, were
      finally evaluated. Eight studies conducted adjustment of risk ratio for potential
      cardiovascular risk factors, 5 studies defined OSA groups as AHI (apnea hypopnea
      index) >=15/hour, whereas the remaining eligible studies used AHI >=5/hour, AHI
      >=10/hour, or AHI >=30/hour as the criteria. According to the result from 5
      studies that use AHI >=15/hour as OSA group, the existence of OSA could, to some
      extent, increase the risk of cardiovascular events (risk ratio 1.59, 95%
      confidence interval 1.22 to 2.06). Meanwhile, hazard ratio was also observed in
      separate co-morbidities, such as cardiac death, all-cause mortality, stroke,
      target lesion revascularization, non-fatal myocardial infarction, hospitalization
      for heart failure, and recurrence of acute coronary syndrome, regardless if the
      estimates are varied among studies. In conclusion, OSA can independently increase
      the risk of cardiovascular events, even after adjustment for confounders. Sleep
      health should be given utmost importance due to its extensive influence on
      cardiovascular disorders.

PMID- 28739037
TI  - Trends in Patient Exposure to Radiation in Percutaneous Coronary Interventions
      Over a 10-Year Period.
AB  - Technological progress has made it possible to reduce the dose of radiation
      delivered by medical x-ray systems. In parallel, interventional coronary
      procedures have become increasingly complex and consequently, last longer. This
      study aimed to compare the estimated dose of radiation received by patients in
      interventional cardiology at 10 years interval (2006 vs 2016). The study
      population included all patients who underwent interventional coronary procedures
      in one of the catheterization laboratories of our institution during 2 periods,
      namely, period 1 from October 2005 to March 2006, and period 2 from November 2015
      to October 2016. The primary end point was the estimated dose of radiation
      received by the patient as assessed by dose area product. In 2016, the estimated
      dose of radiation received by patients who underwent interventional coronary
      procedures was on average 78% lower than that received in 2006 (p <0.0001),
      whereas the fluoroscopy time increased by 54% on average over the same period (p
      <0.0001). By multivariate analysis, including age, approach, body mass index,
      fluoroscopy time, and performance of angioplasty, the reduction in radiation
      remained significant. The radial approach was significantly associated with an
      increased estimated dose of radiation received (p <0.0001). In conclusion, the
      estimated dose of radiation received by patients who underwent interventional
      cardiology procedures has been reduced by 78% over the last decade.

PMID- 28739038
TI  - Anesthetic and Perioperative Management of Patients With Brugada Syndrome.
AB  - Brugada syndrome (BrS) is an arrhythmogenic disease reported to be one among the
      leading causes of cardiac death in subjects under the age of 40 years. In these
      patients, episodes of lethal arrhythmias may be induced by several factors or
      situations, and for this reason, management during anesthesia and surgery must
      provide some precautions and drugs restrictions. To date, it is difficult to
      formulate guidelines for anesthetic management of patients with BrS because of
      the absence of prospective studies, and there is not a definite recommendation
      for neither general nor regional anesthesia, and there are no large studies in
      merit. For this reason, in the anesthesia management of patients with BrS, the
      decision of using each drug must be made after careful consideration and always
      in controlled conditions, avoiding other factors that are known to have the
      potential to induce arrhythmias and with a close cooperation between anesthetists
      and cardiologists, which is essential before and after surgery. In conclusion,
      given the absence of large studies in literature, we want to focus on some
      general rules, which resulted from case series and clinical practice, to be
      followed during the perioperative and anesthetic management of patients with BrS.

PMID- 28739039
TI  - Quantifying Pharmaceutical Film Coating with Optical Coherence Tomography and
      Terahertz Pulsed Imaging: An Evaluation.
AB  - Spectral domain optical coherence tomography (OCT) has recently attracted a lot
      of interest in the pharmaceutical industry as a fast and non-destructive modality
      for quantification of thin film coatings that cannot easily be resolved with
      other techniques. Because of the relative infancy of this technique, much of the
      research to date has focused on developing the in-line measurement technique for
      assessing film coating thickness. To better assess OCT for pharmaceutical coating
      quantification, this paper evaluates tablets with a range of film coating
      thickness measured using OCT and terahertz pulsed imaging (TPI) in an off-line
      setting. In order to facilitate automated coating quantification for film coating
      thickness in the range of 30-200MUm, an algorithm that uses wavelet denoising and
      a tailored peak finding method is proposed to analyse each of the acquired A
      scan. Results obtained from running the algorithm reveal an increasing disparity
      between the TPI and OCT measured intra-tablet variability when film coating
      thickness exceeds 100MUm. The finding further confirms that OCT is a suitable
      modality for characterising pharmaceutical dosage forms with thin film coatings,
      whereas TPI is well suited for thick coatings. (c) 2015 Wiley Periodicals, Inc.
      and the American Pharmacists Association J Pharm Sci 104:3377-3385, 2015.

PMID- 28739040
TI  - The Disintegration Process in Microcrystalline Cellulose Based Tablets, Part 1:
      Influence of Temperature, Porosity and Superdisintegrants.
AB  - Disintegration performance was measured by analysing both water ingress and
      tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with
      croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from
      pure MCC with porosities of 10% and 15% showed similar swelling and transport
      kinetics: within the first 15s, tablets had swollen by up to 33% of their
      original thickness and water had fully penetrated the tablet following Darcy flow
      kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower
      transport kinetics, with swelling to only 17% of their original thickness and
      full water penetration reached after 100s, dominated by case II transport
      kinetics. The effect of adding superdisintegrant to the formulation and varying
      the temperature of the dissolution medium between 20 degrees C and 37 degrees C
      on the swelling and transport process was quantified. We have demonstrated that
      TPI can be used to non-invasively analyse the complex disintegration kinetics of
      formulations that take place on timescales of seconds and is a promising tool to
      better understand the effect of dosage form microstructure on its performance. By
      relating immediate-release formulations to mathematical models used to describe
      controlled release formulations, it becomes possible to use this data for
      formulation design. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists
      Association J Pharm Sci 104:3440-3450, 2015.

PMID- 28739041
TI  - Investigation of pH Influence on Skin Permeation Behavior of Weak Acids Using
      Nonsteroidal Anti-Inflammatory Drugs.
AB  - As a continuing effort to understand the skin permeation behavior of weak acids
      and bases, the objectives of the present study were to evaluate skin permeation
      of nonsteroidal anti-inflammatory drugs (NSAIDs) under the influence of pH,
      investigate the mechanism of pH effect, and examine a previous hypothesis that
      the effective skin pH for drug permeation is different from donor solution pH. In
      vitro permeability experiments were performed in side-by-side diffusion cells
      with diclofenac, ibuprofen, flurbiprofen, ketoprofen, and naproxen and human
      skin. The donor solution pH significantly affected skin permeation of NSAIDs,
      whereas no effect of the receiver pH was observed. Similar to previous
      observations, the apparent permeability coefficient versus donor solution pH
      relationships deviated from the predictions (fractions of unionized NSAIDs)
      according to the acid/base theory. The influences of the viable epidermis
      barrier, polar pathway transport, ion permeation across skin, and effective skin
      pH were investigated. The effective pH values for skin permeation determined
      using the NSAIDs (weak acids) in this study were different from those obtained
      previously with a weak base at the same donor solution pH conditions, suggesting
      that the observed permeability-pH relationships could not be explained solely by
      possible pH differences between skin and donor solution. (c) 2015 Wiley
      Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3459
      3470, 2015.

PMID- 28739042
TI  - Intranasal Piperine-Loaded Chitosan Nanoparticles as Brain-Targeted Therapy in
      Alzheimer's Disease: Optimization, Biological Efficacy, and Potential Toxicity.
AB  - Piperine (PIP) is a phytopharmaceutical with reported neuroprotective potential
      in Alzheimer's disease (AD). Oral PIP delivery suffers from its hydrophobicity
      and pre-systemic metabolism. In this article, mono-disperse intranasal chitosan
      nanoparticles (CS-NPs) were elaborated for brain targeting of PIP. Formula
      optimization was based on particle size (PS), zeta potential (ZP), polydispersity
      index (PDI), % entrapment efficiency (% EE), release studies, and transmission
      electron microscopy. AD was induced in 48 male Wistar rats on which full
      behavioral and biochemical testing was conducted. Brain toxicity was assessed
      based on Caspase-3 assay for apoptosis and tumor necrosis factor for
      inflammation. Spherical NPs with optimum % EE (81.70), PS (248.50nm), PDI (0.24),
      and ZP (+56.30mV) were elaborated. PIP-NPs could significantly improve cognitive
      functions as efficient as standard drug (donpezil injection) with additional
      advantages of dual mechanism (Ach esterase inhibition and antioxidant effect). CS
      NPs could significantly alleviate PIP nasal irritation and showed no brain
      toxicity. This work was the first to report additional mechanism of PIP in AD via
      anti-apoptosis and anti-inflammatory effects. To conclude, mucoadhesive CS-NPs
      were successfully tailored for effective, safe, and non-invasive PIP delivery
      with 20-folds decrease in oral dose, opening a gate for a future with lower AD
      morbidity. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists
      Association J Pharm Sci 104:3544-3556, 2015.

PMID- 28739043
TI  - Pocket detection and interaction-weighted ligand-similarity search yields novel
      high-affinity binders for Myocilin-OLF, a protein implicated in glaucoma.
AB  - Traditional structure and ligand based virtual screening approaches rely on the
      availability of structural and ligand binding information. To overcome this
      limitation, hybrid approaches were developed that relied on extraction of ligand
      binding information from proteins sharing similar folds and hence, evolutionarily
      relationship. However, they cannot target a chosen pocket in a protein. To
      address this, a pocket centric virtual ligand screening approach is required.
      Here, we employ a new, iterative implementation of a pocket and ligand-similarity
      based approach to virtual ligand screening to predict small molecule binders for
      the olfactomedin domain of human myocilin implicated in glaucoma. Small-molecule
      binders of the protein might prevent the aggregation of the protein, commonly
      seen during glaucoma. First round experimental assessment of the predictions
      using differential scanning fluorimetry with myoc-OLF yielded 7 hits with a
      success rate of 12.7%; the best hit had an apparent dissociation constant of
      99nM. By matching to the key functional groups of the best ligand that were
      likely involved in binding, the affinity of the best hit was improved by almost
      10,000 fold from the high nanomolar to the low picomolar range. Thus, this study
      provides preliminary validation of the methodology on a medically important
      glaucoma associated protein.

PMID- 28739044
TI  - Essential structure of orexin 1 receptor antagonist YNT-707, Part I: Role of the
      4,5-epoxy ring for binding with orexin 1 receptor.
AB  - The essential structure of the orexin 1 receptor (OX1R) antagonist YNT-707 (2)
      was clarified, particularly the roles to OX1R antagonist activities of the 3-OMe,
      the 4,5-epoxy ring, the 14-hydroxy group, and the orientation of the 6-amide side
      chain. The 3-OMe and 17-sulfonamide group were shown to be essential for the OX1R
      antagonistic activity. The 4,5-epoxy ring plays an important role for the active
      orientation of the 6-amide group. The 14-hydroxy group could lower the activity
      of the 6beta-amide isomer by the interaction of the 14-hydroxy group with the 6
      amide group, which could orient the 6-amide group toward the upper side of the C
      ring. Finally, we proposed the difference in the active conformation between OX1R
      and kappa opioid receptor (KOR), especially in the orientation of the 6-amide
      group which is expected to be a useful guide for medicinal chemists to design
      OX1R ligands.

PMID- 28739045
TI  - Filamin B: The next hotspot in skeletal research?
AB  - Filamin B (FLNB) is a large dimeric actin-binding protein which crosslinks actin
      cytoskeleton filaments into a dynamic structure. Up to present, pathogenic
      mutations in FLNB are solely found to cause skeletal deformities, indicating the
      important role of FLNB in skeletal development. FLNB-related disorders are
      classified as spondylocarpotarsal synostosis (SCT), Larsen syndrome (LS),
      atelosteogenesis (AO), boomerang dysplasia (BD), and isolated congenital talipes
      equinovarus, presenting with scoliosis, short-limbed dwarfism, clubfoot, joint
      dislocation and other unique skeletal abnormalities. Several mechanisms of FLNB
      mutations causing skeletal malformations have been proposed, including delay of
      ossification in long bone growth plate, reduction of bone mineral density (BMD),
      dysregulation of muscle differentiation, ossification of intervertebral disc
      (IVD), disturbance of proliferation, differentiation and apoptosis in
      chondrocytes, impairment of angiogenesis, and hypomotility of osteoblast,
      chondrocyte and fibroblast. Interventions on FLNB-related diseases require
      prenatal surveillance by sonography, gene testing in high-risk carriers, and
      proper orthosis or orthopedic surgeries to correct malformations including
      scoliosis, cervical spine instability, large joint dislocation, and clubfoot.
      Gene and cell therapies for FLNB-related diseases are also promising but require
      further studies.

PMID- 28739046
TI  - CNVbase: Batch identification of novel and rare copy number variations based on
      multi-ethnic population data.

PMID- 28739048
TI  - Weight loss maintenance: a losing battle?

PMID- 28739047
TI  - Overexpression of Stella improves the efficiency of nuclear transfer
      reprogramming.

PMID- 28739049
TI  - Polyporus and Bupleuri radix effectively alter peripheral circadian clock phase
      acutely in male mice.
AB  - In mammals, daily physiological events are precisely regulated by an internal
      circadian clock system. An important function of this system is to readjust the
      phase of the clock daily. In Japan, traditional herb medicines, so-called crude
      drugs (Shoyaku), are widely used for many diseases, and some are reported to
      affect circadian clock impairment, suggesting that some of them might have an
      ability to modify clock gene expression rhythms. Therefore, from selected 40
      crude drugs, finding candidates that control the circadian clock phases was the
      first purpose of this study. As there are several crude drugs used for liver-
      and/or kidney-related diseases, the second aim of the present study was to find
      some crude drugs affecting liver/kidney circadian clock in vivo. To assess phase
      changes in the daily circadian rhythm, bioluminescence from the core clock gene
      product Period 2 was continuously monitored in mouse embryonic fibroblasts in
      vitro and in some peripheral tissues (kidney, liver, and submandibular gland) of
      PERIOD2::LUCIFERASE knock-in mice in vivo. In our screening, Polyporus and
      Bupleuri radix were found to be good candidates to effectively manipulate the
      peripheral circadian clock phase acutely, with stimulation time-of-day dependency
      in vitro as well as in vivo. Interestingly, Polyporus and Bupleuri radix are
      traditional herb medicines use for treating edema and promoting diuresis, and for
      chronic hepatitis, respectively. These crude drugs may be therefore good
      modulators of the circadian peripheral clocks including liver and kidney, and
      circadian clock genes become new molecular targets for these crude drugs.

PMID- 28739050
TI  - Reduced water intake deteriorates glucose regulation in patients with type 2
      diabetes.
AB  - Epidemiological research has demonstrated that low daily total water intake is
      associated with increased diagnosis of hyperglycemia. Possible mechanisms for
      this increase include hormones related to the hypothalamic pituitary axis as well
      as the renin-angiotensin-aldosterone system (RAAS). Therefore, the hypothesis of
      the present study was that acute low water intake would result in differential
      hormonal profiles and thus impaired blood glucose regulation during an oral
      glucose tolerance test (OGTT) in people with type 2 diabetes mellitus (T2DM).
      Nine men (53 +/- 9 years, 30.0 +/- 4.3 m?kg-2, 32% +/- 6% body fat) diagnosed
      with T2DM completed OGTTs in euhydrated (EUH) and hypohydrated (HYP) states in
      counterbalanced order. Water restriction led to hypohydration of -1.6% of body
      weight, with elevated plasma (EUH: 288 +/- 4, HYP: 298 +/- 6 mOsm.kg-1; P < .05)
      and urine (EUH: 512 +/- 185, HYP: 994 +/- 415 mOsm.kg-1; P < .05) osmolality.
      There was a significant main effect of condition for serum glucose (at time 0
      minute 9.5 +/- 4.2 vs 10.4 +/- 4.4 mmol?L-1 and at time 120 minutes 19.1 +/- 4.8
      vs 21.0 +/- 4.1 mmol?L-1 for EUH and HYP, respectively; P < .001) but not insulin
      (mean difference between EUH and HYP -12.1 +/- 44.9 pmol?L-1, P = .390). An
      interaction between time and condition was observed for cortisol: decrease from
      minute 0 to 120 in EUH (-85.3 +/- 82.1 nmol?L-1) vs HYP (-25.0 +/- 43.0 nmol?L-1;
      P = .017). No differences between conditions were found within RAAS-related
      hormones. Therefore, we can conclude that 3 days of low total water intake in
      people with T2DM acutely impairs blood glucose response during an OGTT via
      cortisol but not RAAS-mediated glucose regulation.

PMID- 28739051
TI  - Effectiveness of nutritional and exercise interventions to improve body
      composition and muscle strength or function in sarcopenic obese older adults: A
      systematic review.
AB  - Although sarcopenic obesity (SO) poses a major public health concern, a robust
      approach for the optimization of body composition and strength/function in SO has
      not yet been established. The purpose of this systematic review was to assess the
      effectiveness of nutritional (focusing on energy and protein modulation) and
      exercise interventions, either individually or combined, on body composition and
      strength/function in older adults with SO. MEDLINE, the Cochrane Central Register
      of Controlled Trials, CINAHL and SPORTDiscus were searched. Main inclusion
      criteria comprised sarcopenia as defined by the European Working Group on
      Sarcopenia in Older People (EWGSOP) and obesity defined as % body fat >=40%
      (women) and >=28% (men). Randomized controlled trials (RCTs), randomized
      controlled crossover trials and controlled clinical trials with older adults
      (mean age >=65 years) following a nutritional regimen and/or an exercise training
      program were considered. Out of 109 full text articles identified, only two RCTs
      (61 participants) met the inclusion criteria. One study was a nutritional
      intervention adding 15 g protein.day-1 (via cheese consumption) to the
      participants' habitual diet. The second study was a high-speed circuit resistance
      training intervention. Body composition did not change significantly in either of
      the studies. However, the exercise intervention improved significantly muscle
      strength and physical function. Although this review was limited by the small
      number of eligible studies, it provides evidence for the potential benefits of
      exercise and highlights the necessity for future research to develop effective
      interventions including dietary and exercise regimens to combat sarcopenic
      obesity.

PMID- 28739052
TI  - A 51-item calcium-focused food frequency questionnaire is a reliable tool to
      assess dietary calcium intake in postmenopausal women.
AB  - Given the lack in a valid biomarker to assess dietary calcium intake (dCai),
      reproducible estimation of usual dCai is crucial for better understanding of its
      interaction with health outcomes in specific populations. This study tested the
      hypothesis that a calcium-focused food frequency questionnaire (FFQ) may be used
      to estimate dCai of women >=50 years residing in a multicultural environment
      (Montreal, Canada). One hundred and eight women (age, 63.1+/-7.7 years; 98%
      postmenopausal) completed the FFQ twice and 4 nonconsecutive 24-hour recalls
      (24HRs) over 1 month. Medians of dCai were compared by Wilcoxon signed rank test.
      Reproducibility and relative validity of the FFQ were assessed by Spearman
      correlation (rs) and Cohen's weighted kappa (kappaw). Agreement was further
      assessed by cross-classification by quartiles, Bland-Altman plot, and sensitivity
      and specificity analyses. The median (interquartile range) dCai estimated by the
      FFQ and 24HRs were 723 (524-1033) mg/d and 854 (666-1068) mg/d, respectively
      (P<.001). The FFQs had a strong correlation (rs=0.72, P<.001) and moderate
      agreement (kappaw=0.55). The FFQ and 24HRs were moderately correlated (rs=0.65,
      P<.001). Cross-classification showed moderate agreement (kappaw=0.42), with 85%
      of the participants classified into identical or contiguous quartiles and 2.8%
      into extreme opposite quartiles. According to the Bland-Altman plot, the FFQ
      underestimated dCai with a bias of 99 mg/d (95% limits of agreement, -677 to +480
      mg/d). Sensitivity and specificity of identifying intakes <1000 mg/d were 90% and
      57%, respectively. This FFQ is a useful tool to discriminate dCai <600 and >=1000
      mg/d in postmenopausal women and to rank dCai in epidemiological studies.

PMID- 28739053
TI  - Glucomannan consumption elevates colonic alkaline phosphatase activity by up
      regulating the expression of IAP-I, which is associated with increased production
      of protective factors for gut epithelial homeostasis in high-fat diet-fed rats.
AB  - We previously reported that consumption of glucomannan-containing food (lily
      bulb) modulates gut microbiota and increases gut immunoglobulin A (IgA, index of
      intestinal immune function), mucins (index of intestinal barrier function), and
      colonic alkaline phosphatase (ALP) activity in rats fed a high-fat (HF) diet.
      Small intestinal ALP has an established protective effect in inflammatory
      diseases, whereas little is known about the function of colonic ALP activity. We
      hypothesized that dietary glucomannan would increase colonic ALP activity and the
      gene expression in rats fed an HF diet. To test this hypothesis, male Sprague
      Dawley rats were fed a diet containing 30% lard with or without 4% high or low
      viscous glucomannan (HGM or LGM) for 2 weeks. Dietary HGM and LGM significantly
      increased colonic ALP activity without affecting ALP activity in the small
      intestine. The colonic expression of IAP-I, an ALP gene expressed throughout the
      intestine, was significantly higher in the HGM and LGM groups when compared with
      the control group. The colonic expression of Akp3 and Alpl, other ALP genes, were
      not affected by HGM and LGM. Dietary HGM and LGM significantly elevated fecal
      levels of IgA and mucins and cecal organic acids, including n-butyrate,
      propionate, and lactate. Colon ALP correlated with fecal IgA, mucins, and cecal
      organic acids. The present study showed that dietary glucomannan elevates colonic
      ALP activity by up-regulation of the expression of IAP-I, which might be
      important for protection of gut epithelial homeostasis.

PMID- 28739054
TI  - Plasma trans-fatty acid concentrations continue to be associated with metabolic
      syndrome among US adults after reductions in trans-fatty acid intake.
AB  - No study examined and compared the association between intake of trans-fatty
      acids (TFAs) and risk of metabolic syndrome before and after significant
      reduction of TFA intakes in the US population. We hypothesized that the
      relationship might remain significant after substantial reduction of TFA intakes
      in the population. We used data on 1442 and 2233 adults aged >=20 years from the
      National Health and Nutrition Examination Survey 1999-2000 and 2009-2010,
      respectively. Multivariable logistic regression analysis was used to assess the
      association between plasma TFA concentrations and metabolic syndrome, including
      each of its 5 components. The median plasma TFA concentrations were reduced from
      79.8 MUmol/L in 1999-2000 to 36.9 MUmol/L in 2009-2010. The fully adjusted
      prevalence ratios comparing the highest vs the lowest quintile of plasma TFA
      concentrations in 1999-2000 were 3.43 (95% confidence interval, 2.39-4.92) for
      metabolic syndrome, 1.72 (1.38-2.14) for large waistline, 8.25 (6.34-10.74) for
      high triglycerides, 1.96 (1.46-2.62) for low high-density lipoprotein
      cholesterol, 1.14 (0.85-1.55) for high blood pressure, and 1.48 (1.19-1.85) for
      high fasting glucose, respectively. The corresponding prevalence ratios in 2009
      2010 were 2.93 (2.41-3.54), 1.62 (1.39-1.89), 14.93 (9.28-24.02), 3.09 (2.18
      4.37), 1.27 (1.11-1.46), and 1.24 (1.06-1.46), respectively. The pattern of
      association between TFAs and metabolic syndrome and its components did not differ
      by cycles. The observed associations were consistent across the subgroups
      examined. Despite a 54% decline in plasma TFA concentrations from 1999-2000 to
      2009-2010, it was positively associated with risk of metabolic syndrome and its
      individual components except for blood pressure in 1999-2000. Our findings
      support Food and Drug Administration initiatives to remove TFAs from the
      industrially-produced foods.

PMID- 28739055
TI  - Dietary fatty acids were not independently associated with lipoprotein subclasses
      in elderly women.
AB  - Dietary fatty acids are known to affect serum lipoproteins; however, little is
      known about the associations between consumption of dietary fatty acids and
      lipoprotein subclasses. In this study, we hypothesized that there is an
      association between dietary fatty acids and lipoprotein subclasses and
      investigated the cross-sectional association of dietary fat intake with
      subclasses of lipoproteins in elderly women. Altogether, 547 women (aged >=65
      years) who were part of OSTPRE cohort participated. Dietary intake was assessed
      by 3-day food records, lifestyle, and health information obtained through self
      administrated questionnaires, and lipoprotein subclasses were determined by
      nuclear magnetic resonance spectroscopy. To analyze the associations between
      fatty acids and lipoprotein subclasses, we used Pearson and Spearman correlation
      coefficients and the analysis of covariance (ANCOVA) test with, adjustment for
      physical activity, body mass index, age, smoking status, and intake of lipid
      lowering drugs. There were significant correlations between saturated fatty acids
      (SFA; % of energy) and concentrations of large, medium, and small low-density
      lipoproteins (LDL); total cholesterol in large, medium, and small LDL; and
      phospholipids in large, medium, and small LDL, after correction for multiple
      testing. After adjustment for covariates, the higher intake of SFA was associated
      with smaller size of LDL particles (P = .04, ANCOVA) and lower amount of
      triglycerides in small very low-density lipoproteins (P = .046, ANCOVA). However,
      these associations did not remain significant after correction for multiple
      testing. In conclusion, high intake of SFA may be associated with the size of LDL
      particles, but the results do not support significant, independent associations
      between dietary fatty acids and lipoprotein subclasses.

PMID- 28739056
TI  - Supplementation with Vitis vinifera L. skin extract improves insulin resistance
      and prevents hepatic lipid accumulation and steatosis in high-fat diet-fed mice.
AB  - Nonalcoholic fatty liver disease is one of the most common complications of
      obesity. The Vitis vinifera L. grape skin extract (ACH09) is an important source
      of polyphenols, which are related to its antioxidant and antihyperglycemic
      activities. We hypothesized that ACH09 could also exert beneficial effects on
      metabolic disorders associated with obesity and evaluated ACH09's influence on
      high-fat (HF) diet-induced hepatic steatosis and insulin resistance in C57BL/6
      mice. The animals were fed a standard diet (10% fat, control) or an HF diet (60%
      fat, HF) with or without ACH09 (200mg/[kg d]) for 12weeks. Our results showed
      that ACH09 reduced HF diet-induced body weight gain, prevented hepatic lipid
      accumulation and steatosis, and improved hyperglycemia and insulin resistance.
      The underlying mechanisms of these beneficial effects of ACH09 may involve the
      activation of hepatic insulin-signaling pathway because the expression of
      phosphorylated insulin receptor substrate-1, phosphatidylinositol 3-kinase,
      phosphorylated Akt serine/threonine kinase 1, and glucose transporter 2 was
      increased by ACH09 and correlated with improvement of hyperglycemia,
      hyperinsulinemia, and insulin resistance. ACH09 reduced the expression of the
      lipogenic factor sterol regulatory-element binding protein-1c in the liver and
      upregulated the lipolytic pathway (phosphorylated liver kinase B1/phosphorylated
      adenosine-monophosphate-activated protein kinase), which was associated with
      normal hepatic levels of triglyceride and cholesterol and prevention of
      steatosis. ACH09 prevented the hepatic oxidative damage in HF diet-fed mice
      probably by restoration of antioxidant activity. In conclusion, ACH09 protected
      mice from HF diet-induced obesity, insulin resistance, and hepatic steatosis. The
      regulation of hepatic insulin signaling pathway, lipogenesis, and oxidative
      stress may contribute to ACH09's protective effect.

PMID- 28739057
TI  - Facts and Opinions: Use Evidence to Make the Call.

PMID- 28739058
TI  - Acupressure in Management of Postoperative Nausea and Vomiting in High-Risk
      Ambulatory Surgical Patients.
AB  - PURPOSE: The purpose of this randomized blinded placebo-controlled research study
      was to investigate the effect of acupressure over 24 hours postoperatively for
      ambulatory surgical patients who are identified as high risk for PONV. DESIGN: A
      randomized blinded placebo-controlled study design was implemented. METHODS:
      Study enrollment criteria included four of five risk factors as defined in 2006
      by American Society of PeriAnesthesia Nurses PONV/postdischarge nausea and
      vomiting guidelines: female, PONV history or motion sickness, nonsmoker, and
      volatile gas general anesthetic. One hundred ten patients were randomly assigned
      to an intervention (N = 57) acupressure bead patch or control (N = 53) sham
      acupressure patch group. Patients rated PONV on scale (0 to 10). FINDINGS:
      Acupressure use at P6 preoperatively was statistically significant in reducing
      PONV in all three postoperative phases. One hundred ten patients were enrolled;
      93 patients finished the study's three phases and nine were admitted
      postoperatively. CONCLUSIONS: Acupressure is an effective minimal risk and low
      cost adjunctive therapy for prevention and treatment in ambulatory surgical
      patients at high risk for PONV. Further studies using other acupressure points
      should be conducted.

PMID- 28739059
TI  - Postoperative Pain and Analgesia in Children Undergoing Palatal Surgery: A
      Retrospective Chart Review.
AB  - PURPOSE: Pediatric patients undergoing palatal surgery may experience significant
      postoperative pain. Undertreatment of acute postoperative pain may impact
      postoperative bleeding and recovery. The primary objectives of this study were to
      evaluate the severity of acute postoperative pain scores, analgesia management,
      and discharge times after palatal surgery. DESIGN AND METHODS: A retrospective
      chart review was performed for all patients aged <18 years, born with cleft
      palate who underwent palatal surgery over a 1-year period. The primary outcome
      variable was the highest pain score recorded by the nursing staff at various time
      frames postoperatively. FINDINGS: Overall, the infant/toddler group demonstrated
      higher postoperative pain scores throughout the first 24 hours (1- to 6-hour
      period, P = .015). The duration of hospital stay was significantly greater in the
      infant/toddler age group (P < .001). CONCLUSION: The results of our study
      indicate that frequent pain monitoring, multimodal approach, and "round-the
      clock" analgesics may be warranted in this vulnerable patient population.

PMID- 28739060
TI  - Organizational Support, Workload, and Intent to Stay: Work Environment
      Perceptions in Perianesthesia Nursing Units.
AB  - PURPOSE: The purpose of this ASPAN study was to understand perianesthesia nurses'
      perception of their work environments in regards to organizational support,
      workload, intent to stay, and overall nurse satisfaction. DESIGN: A descriptive
      design was used with survey methodology. METHOD: An online survey was sent to
      American Society of PeriAnesthesia Nurses members. The Individual Workload
      Perception Scale-Revised was used. A total of 2,121 American Society of
      PeriAnesthesia Nurses members participated (21% response rate). FINDINGS: Fifty
      three percent reported that their nurse manager had responsibilities for three or
      more units. Having an assigned preceptor had a significant difference with
      organizational support, workload, intent to stay, and overall nurse satisfaction.
      Certified nurses reported significantly better perceptions of workload and intent
      to stay. CONCLUSION: This is the first national glimpse of the perianesthesia
      work environment and its influence on nurse outcomes. These results can be used
      to improve the perianesthesia work environment.

PMID- 28739061
TI  - Communication Between Postdelivery Mothers in the PACU and Newborns in Israel.
AB  - BACKGROUND: Perioperative, maternity, and newborn nurses discovered a solution
      using modern technology to facilitate earlier "connection" between postcesarean
      section mothers and their newborns using televised video conference (VC) or
      telemedicine. Videoconferencing used as a support in cases of separation after
      childbirth can facilitate a first "meeting" closer to the time of birth. AIM: The
      aim of this study was to design and validate the use of video conferencing to
      facilitate "bonding" between postdelivery cesarean delivery mothers who are
      separated from their infants. DESIGN: Mixed quantitative and qualitative. METHOD:
      Mothers (n = 29) completed questionnaires investigating immediate postpartum
      needs for communication with their newborns. Questionnaire analysis revealed the
      primary need is connection and communication. The nursing team developed a VC
      system between postanesthesia care unit and newborn unit including nurse-mother
      instruction. Mothers (n = 10) were qualitatively queried regarding their VC
      experience. RESULTS: When prioritizing, mothers found the most important need is
      to see the infant. Eight themes were found: revelation, calming effect, closer
      look at the baby, video better than picture, excitement, short-timing sufficient,
      provision of strength, and confidence. CONCLUSION: The nursing team successfully
      coordinated new technologies to the hospital setting to fulfill mothers' needs.
      After evaluation of mothers' impressions, it was found that this technology is
      adaptable to hospital setting and postdelivery environment. Most importantly,
      this method contributes to improved well-being for postpartum mothers.

PMID- 28739062
TI  - Effect of Head and Neck Immobilization on Postspinal Headache: A Randomized
      Controlled Trial.
AB  - PURPOSE: The purpose of the study was to determine the effect of head and neck
      immobilization on postdural puncture headache (PDPH) through the use of cervical
      collars. DESIGN: This was a fully randomized controlled trial. METHOD: The sample
      group of the study consisted of 120 patients. Patients in the experimental group
      were followed up by using the appropriate cervical collar after the operation.
      The cervical collar was kept on until mobilization. Follow-ups of patients in the
      control group continued without limiting head and neck movements. Headaches of
      patients in the experimental and control groups at 24, 48, and 72 hours after the
      operation were determined. FINDINGS: The average age of the patients in the
      experimental group was 22.70 +/- 2.72, whereas it was 22.93 +/- 3.29 in the
      control group. The mean body mass index of the experimental group and control
      group was 24.24 +/- 2.62 and 23.46 +/- 3.03, respectively. The mean scores of the
      patients in the experimental and control groups on the Numeric Rating Scale were
      statistically significant in favor of patients in the experimental group in the
      interval of 24 and 48 hours (P < .05) and was not statistically significant after
      72 hours (P > .05). CONCLUSION: This study showed that prolonged immobility of
      the neck, in addition to bed rest, could not prevent PDPHs. The use of a cervical
      collar may help to delay PDPHs. may help to delay PDPHs.

PMID- 28739063
TI  - Patients' Opinions of OR Nurses and Environments in the Postoperative Period.
AB  - PURPOSE: To determine patients' opinions of operating room (OR) nurses and
      environments in the postoperative period. DESIGN: A descriptive study. METHODS:
      The data were collected by using researcher developed forms that defined
      patients' opinions of OR nurses and environments and were given to the patients
      on the first postoperative day. FINDING: The final sample consisted of a total of
      208 patients who underwent surgery with regional anesthesia. Percentage
      measurements were used in the assessment of data. The majority (69.3%) of nurses
      did not introduce themselves to their patients and 61.3% failed to introduce the
      OR environments to their patients. Patients explored their (ORs) in the range of
      62% and 90% and considered these locations to be calm and reliable environments
      where their needs were met and their communications with the staff were positive.
      The rate of patients who felt that their ORs were not cold was 35.3%.
      CONCLUSIONS: In this study, most patients were not aware that OR nursing played
      an important role in a postive patient perception of the OR. Most OR nurses did
      not introduce themselves to patients while providing nursing care, and patients
      were not aware of who provided this service to them. In light of these findings,
      it is recommended that nurses introduce themselves to patients in the OR when
      beginning care of the patient. Moreover, special effort should be made regarding
      maintenance of normal body temperature of patients in the OR.

PMID- 28739064
TI  - Meta-Analysis of the Ease of Care From a Patients' Perspective Comparing Fentanyl
      Iontophoretic Transdermal System Versus Morphine Intravenous Patient-Controlled
      Analgesia in Postoperative Pain Management.
AB  - PURPOSE: The purpose of this meta-analysis was to evaluate patients' assessment
      of fentanyl iontophoretic transdermal system (ITS) and morphine intravenous
      patient-controlled analgesia (IV PCA) ease of care (EOC) using a validated
      patient EOC questionnaire. Fentanyl ITS is a preprogrammed, needle-free PCA
      system used for the management of acute pain in postoperative patients. METHODS:
      This meta-analysis assessed the patient EOC of fentanyl ITS and morphine IV PCA
      using data from three randomized, active-comparator trials in adult postoperative
      patients with moderate-to-severe pain. All three studies utilized a validated
      patient EOC questionnaire which consists of 23 items grouped into seven subscales
      (confidence with device, comfort with device, movement, dosing confidence, pain
      control, knowledge/understanding, and satisfaction). Each item is scored on a six
      point Likert scale. The weighted mean difference between treatments was
      calculated for the overall EOC and for each of the seven subscales. RESULTS: The
      EOC analyses were based on responses to questionnaires from 1,943 patients
      treated with either fentanyl ITS (n = 961) or morphine IV PCA (n = 982). There
      was a statistically significant advantage in favor of fentanyl ITS over morphine
      IV PCA in terms of overall EOC (weighted mean difference = 0.28; 95% confidence
      interval (0.22 to 0.34); P < 0.0001). Five of the seven subscales (confidence
      with device, comfort with device, movement, dosing confidence, and
      knowledge/understanding) on the patient EOC questionnaire showed a statistically
      significant advantage for fentanyl ITS versus morphine IV PCA. The two subscales
      that did not show any difference were pain control (P = 0.7303) and satisfaction
      (0.0561). CONCLUSION: In this meta-analysis, fentanyl ITS is associated with some
      advantages in terms of an EOC profile from a patients' perspective when compared
      with morphine IV PCA.

PMID- 28739065
TI  - Meta-Analysis of the Ease of Care From the Nurses' Perspective Comparing Fentanyl
      Iontophoretic Transdermal System (ITS) Vs Morphine Intravenous Patient-Controlled
      Analgesia (IV PCA) in Postoperative Pain Management.
AB  - PURPOSE: The aim of this meta-analysis was to compare the ease of care (EOC) of
      fentanyl iontophoretic transdermal system (ITS) vs the morphine intravenous
      patient-controlled analgesia (IV PCA) as assessed by the nurse. DESIGN: Meta
      analysis of three phase 3B randomized active-comparator trials. METHODS: This
      meta-analysis according to Cochrane's approach assessed EOC using a validated
      nurse questionnaire (22 items grouped into three subscales, which include time
      efficiency, convenience, and satisfaction) in adult patients treated with
      fentanyl ITS or morphine IV PCA for postoperative pain management. The weighted
      mean difference (WMD) between treatments was calculated. FINDING: EOC analyses
      were based on responses to questionnaires from 848 (fentanyl ITS) and 761
      (morphine IV PCA) nurses. Fentanyl ITS was reported to provide significant
      advantages compared with morphine IV PCA in terms of nurses' overall EOC (WMD = 
      0.57, P < .0001) and each of the subscales: time efficiency (WMD = -0.58, P <
      .0001), convenience (WMD = -0.57, P < .0001), and satisfaction (WMD = -0.47, P <
      .0001). CONCLUSIONS: In this meta-analysis, fentanyl ITS is associated with a
      superior EOC profile from the nurses' perspective than morphine IV PCA.

PMID- 28739066
TI  - A Turkish Version of the Critical-Care Pain Observation Tool: Reliability and
      Validity Assessment.
AB  - PURPOSE: The study aim was to evaluate the validity and reliability of the
      Critical-Care Pain Observation Tool in critically ill patients. DESIGN: A
      repeated measures design was used for the study. METHODS: A convenience sample of
      66 patients who had undergone open-heart surgery in the cardiovascular surgery
      intensive care unit in Ordu, Turkey, was recruited for the study. The patients
      were evaluated by using the Critical-Care Pain Observation Tool at rest, during a
      nociceptive procedure (suctioning), and 20 minutes after the procedure while they
      were conscious and intubated after surgery. FINDING: The Turkish version of the
      Critical-Care Pain Observation Tool has shown statistically acceptable levels of
      validity and reliability. Inter-rater reliability was supported by moderate-to
      high-weighted kappa coefficients (weighted kappa coefficient = 0.55 to 1.00). For
      concurrent validity, significant associations were found between the scores on
      the Critical-Care Pain Observation Tool and the Behavioral Pain Scale scores.
      Discriminant validity was also supported by higher scores during suctioning (a
      nociceptive procedure) versus non-nociceptive procedures. The internal
      consistency of the Critical-Care Pain Observation Tool was 0.72 during a
      nociceptive procedure and 0.71 during a non-nociceptive procedure. CONCLUSIONS:
      The validity and reliability of the Turkish version of the Critical-Care Pain
      Observation Tool was determined to be acceptable for pain assessment in critical
      care, especially for patients who cannot communicate verbally.

PMID- 28739067
TI  - The Unique Role of the Pediatric Clinical Research Nurse in Anesthesia: An
      Interdisciplinary Collaboration.
AB  - This article describes the distinctive function of the pediatric clinical
      research nurse (CRN) in the anesthesia setting. The pediatric CRN in anesthesia
      acts as a liaison between families and the research team and is the major nexus
      between the principal investigator or anesthesiologist on a study, and the
      collaborating surgeons from many different departments. This is unique because
      the CRNs collaborate with physicians in specialties that can include plastics,
      urology, neurosurgery, orthopaedics, otolaryngology, cardiology, critical care,
      and many other departments. The profession requires a breath of knowledge ranging
      from clinical understanding of diseases, surgical procedures, and recovery to
      cognitive and developmental stages, to expertise in the research protocol
      process. Our objective was to describe these specialized activities of the
      pediatric anesthesia CRN, with focus on care coordination, communication, and
      continuity of care. Defining this role will enhance the quality of clinical
      research conducted by the CRN in anesthesia and may influence the development of
      novel medical treatments.

PMID- 28739068
TI  - Management of Emergence Delirium in Adult PTSD Patients: Recommendations for
      Practice.
AB  - Emergence delirium is a known phenomenon which occurs after general anesthesia in
      approximately 5% of the general population. However, individuals who have been
      diagnosed with post-traumatic stress disorder may present with symptoms
      refractory to conventional methods of reorientation. In the past several years,
      literature has begun to address the problem, but no standardized guidelines exist
      at present. The authors synthesize the available literature, combining data with
      evidence-driven principles from multiple disciplines, to submit an initial set of
      guidelines until research either supports or disproves these recommendations.

PMID- 28739069
TI  - Critical Care Connection Nurses' Caring Behaviors.

PMID- 28739070
TI  - Cybersecurity: A Real Threat to Patient Safety.

PMID- 28739071
TI  - Sustain and Shape the Culture of Your Unit.

PMID- 28739072
TI  - Opioid Stewardship.

PMID- 28739073
TI  - Considering the Sample.

PMID- 28739074
TI  - When the Worst Happens: Cardiac Arrest in the Pediatric PACU.

PMID- 28739075
TI  - Adolescence: A Time of Transition.

PMID- 28739076
TI  - A Meta-analysis comparing the effect of anatomical resection vs. non-anatomical
      resection on the long-term outcomes for patients undergoing hepatic resection for
      hepatocellular carcinoma.
AB  - BACKGROUND: This study aimed to compare the outcomes of patients undergoing
      anatomical resection (AR) versus non-anatomical resection (NAR) for
      hepatocellular carcinoma (HCC) from the published comparative studies within the
      literatures. METHODS: A meta-analysis of studies published from 2001 to 2010 were
      conducted using RevMan 5.0. Measured outcomes were morbidity, mortality,
      recurrence and 5 year overall (OS) and disease free (DFS) survival. RESULTS:
      Seventeen observational studies involving 3129 patients were analyzed: 1626 (52%)
      in AR group and 1503 (48%) in NAR group. The 5-year OS (RR, 1.18; 95% CI, 1.03
      1.36; P = 0.018) and DFS (RR, 1.56; 95% CI, 1.23-1.97; P < 0.001) were
      significantly greater in the AR group than the NAR group, while the overall
      recurrence was significantly lower (RR, 0.84; 95% CI, 0.75-0.94; P < 0.001).
      There were no significant differences in mortality (RR, 1.00; 95% CI, 0.80-1.25;
      P = 0.980) or morbidity (OR, 0.97; 95% CI, 0.48-1.99; P = 0.943) between the AR
      and NAR groups. CONCLUSION: AR for HCC is superior to NAR considering its higher
      5-year OS and DFS rates and lower overall recurrence rate. Heterogeneity
      detection within the analysis suggests these results should be interpreted with
      caution and further well designed studies are required to address this issue.

PMID- 28739078
TI  - Mutualisms Are Not on the Verge of Breakdown.
AB  - Mutualisms teeter on a knife-edge between conflict and cooperation, or so the
      conventional wisdom goes. The costs and benefits of mutualism often depend on the
      abiotic or biotic context in which an interaction occurs, and experimental
      manipulations can induce shifts in interaction outcomes from mutualism all the
      way to parasitism. Yet, research suggests that mutualisms rarely turn parasitic
      in nature. Similarly, despite the potential for 'cheating' to undermine mutualism
      evolution, empirical evidence for fitness conflicts between partners and, thus,
      selection for cheating in mutualisms is scant. Furthermore, mutualism seldom
      leads to parasitism at macroevolutionary timescales. Thus, I argue here that
      mutualisms do not deserve their reputation for ecological and evolutionary
      instability, and are not on the verge of breakdown.

PMID- 28739079
TI  - Individual Confidence-Weighting and Group Decision-Making.
AB  - Group-living species frequently pool individual information so as to reach
      consensus decisions such as when and where to move, or whether a predator is
      present. Such opinion-pooling has been demonstrated empirically, and theoretical
      models have been proposed to explain why group decisions are more reliable than
      individual decisions. Behavioural ecology theory frequently assumes that all
      individuals have equal decision-making abilities, but decision theory relaxes
      this assumption and has been tested in human groups. We summarise relevant theory
      and argue for its applicability to collective animal decisions. We consider
      selective pressure on confidence-weighting in groups of related and unrelated
      individuals. We also consider which species and behaviours may provide evidence
      of confidence-weighting, paying particular attention to the sophisticated vocal
      communication of cooperative breeders.

PMID- 28739077
TI  - T-bet-expressing B cells during HIV and HCV infections.
AB  - T-bet-expressing B cells, first identified as perpetuators of autoimmunity, were
      recently shown to be critical for murine antiviral responses. While their role in
      human viral infections remains unclear, B cells expressing T-bet or demonstrating
      a related phenotype have been described in individuals chronically infected with
      HIV or HCV, suggesting these cells represent a component of human antiviral
      responses. In this review, we discuss the induction of T-bet in B cells following
      both HIV and HCV infections, the factors driving T-bet+ B cell expansions, T
      bet's relationship to atypical memory B cells, and the consequences of T-bet
      induction. We propose potential antiviral roles for T-bet+ B cells and discuss
      whether this population poses any utility to the HIV and HCV immune responses.

PMID- 28739080
TI  - Tools for Enhancement and Quality Improvement of Peer Assessment and Clinical
      Care in Endocrinology and Metabolism.
AB  - Members of the College of Physicians and Surgeons of Ontario Endocrinology and
      Metabolism Peer Review Network have been involved in a quality improvement
      project to help standardize the peer assessment of physicians practicing in
      endocrinology and metabolism. This has included developing state-of-the-art
      summaries of common endocrine problems by Canadian experts in endocrinology and
      metabolism. These tools have been developed in response to the educational needs,
      as identified by peer reviewers, of practicing endocrinologists in Ontario. These
      pedagogical tools aim not only to standardize the documentation of the clinical
      performance of endocrinologists but also to make the process more transparent and
      to improve the quality of patient care in Ontario. This article summarizes the
      project and also provides the tools developed for the endocrinology and
      metabolism section of the College of Physicians and Surgeons of Ontario.

PMID- 28739081
TI  - Quantitative Ultrasound (QUS) in the Management of Osteoporosis and Assessment of
      Fracture Risk.
AB  - The use of quantitative ultrasound (QUS) for a variety of skeletal sites,
      associated with the absence of technology-specific guidelines, has created
      uncertainty with respect to the application of QUS results to the management of
      individual patients in clinical practice. However, when prospectively validated
      (this is not the case for all QUS devices and skeletal sites), QUS is a proven,
      low-cost, and readily accessible alternative to dual-energy X-ray absorptiometry
      (DXA) measurements of bone mineral density (BMD) for the assessment of fracture
      risk. Indeed, the clinical use of QUS to identify subjects at low or high risk of
      osteoporotic fracture should be considered when central DXA is unavailable.
      Furthermore, the use of QUS in conjunction with clinical risk factors
      (CRF),allows for the identification of subjects who have a low and high
      probability of osteoporotic fracture. Device- and parameter-specific thresholds
      should be developed and cross-validated to confirm the concurrent use of QUS and
      CRF for the institution of pharmacological therapy and monitoring therapy.

PMID- 28739082
TI  - Osteoporosis Risk Calculators.
AB  - Osteoporosis is a silent disease until fractures occur, patient recognition is
      the greatest clinical challenge. Although more than 20 million women in the US
      are estimated to have established osteoporosis the majority are not appropriately
      identified. Bone densitometry is the current gold standard for diagnosis of
      osteoporosis; but may not be feasible or cost-effective to recommend for all
      postmenopausal women. Therefore, questionnaires incorporating risk factors have
      been developed to aid the clinician in identifying women with osteoporosis. We
      will review Qfracture, CAnadian Risk for Osteoporosis Calculator (CAROC), the
      Simple Calculated Osteoporosis Risk Index (SCORE), the Osteoporosis Risk
      Assessment Index (ORAI), the Osteoporotic Self-assessment Tool (OST), ABONE, and
      the United States Preventive Services Task Force recommendations.

PMID- 28739083
TI  - Assessment of Osteoporosis Fracture Risk: Preface.

PMID- 28739084
TI  - The repeatability and characteristics of right ventricular longitudinal strain
      imaging by speckle-tracking echocardiography in healthy dogs.
AB  - INTRODUCTION: To assess the repeatability and characteristics of
      echocardiographic indices of the right ventricular (RV) function derived from
      speckle-tracking echocardiography. ANIMALS: Fourteen laboratory Beagles and 103
      privately owned dogs without cardiac disease were involved in this study.
      MATERIALS AND METHODS: Right ventricular longitudinal strain, strain rate, and a
      strain-related index for assessing RV dyssynchrony derived from speckle-tracking
      echocardiography were obtained by two different observers using five Beagles.
      Within-day, between-day, and interobserver coefficients of variation and the
      intraclass correlation coefficient of speckle-tracking echocardiography indices
      were determined. Both speckle-tracking echocardiography and conventional indices
      of RV function, including the peak velocity of systolic tricuspid annular motion,
      tricuspid annulus plane systolic excursion, fractional area change, and the Tei
      index, were obtained from 14 Beagles and 103 privately owned dogs. Relationships
      between echocardiographic indices and the body weight, heart rate, age, and sex
      were estimated by regression analysis. RESULTS: Speckle-tracking
      echocardiographic indices showed good within-day repeatability, between-day and
      interobserver repeatability were moderate to good. In large dogs, RV longitudinal
      strain, strain rate, and fractional area change were significantly decreased,
      while the index of RV dyssynchrony, systolic tricuspid annular motion, tricuspid
      annulus plane systolic excursion, and the Tei index were increased. All speckle
      tracking and conventional echocardiographic indices were correlated with the body
      weight. DISCUSSION AND CONCLUSIONS: The speckle-tracking echocardiography indices
      were highly repeatable and body weight affected speckle-tracking echocardiography
      indices in dogs. Further studies are needed to apply speckle-tracking
      echocardiography indices in dogs with cardiac disease.

PMID- 28739085
TI  - [Authors'response to the letter on the article "Teledermatology in a prison
      setting: A retrospective study of 500 expert opinions"].

PMID- 28739086
TI  - A preclinical study on the combined effects of repeated eltoprazine and
      preladenant treatment for alleviating L-DOPA-induced dyskinesia in Parkinson's
      disease.
AB  - Eltoprazine, a serotonergic (5-HT)1A/B receptor agonist, is a potential treatment
      for L-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD) but notably
      compromises the anti-parkinsonian effects of L-DOPA, as seen in rodent and monkey
      models of PD. Preladenant, a selective adenosine A2a receptor antagonist,
      mediates modest anti-parkinsonian effects in parkinsonian monkeys. In a recent
      investigation, combined eltoprazine and preladenant treatment with a sub
      threshold dose of L-DOPA acutely attenuated dyskinesia without exacerbating PD
      disability in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated
      macaques. The aim of this study was to investigate the daily repeated treatment
      effects of eltoprazine (1mg/kg) alone, and in combination with preladenant
      (5mg/kg), on the motor symptoms of PD and LID in MPTP-treated macaques. The anti
      dyskinetic and -parkinsonian effects of combinative drug administration with a
      sub-threshold dose of L-DOPA were measured over 14 days. Eltoprazine treatment
      alone produced a near-complete suppression of dyskinesia but consistently
      increased parkinsonism. The administration of preladenant with eltoprazine
      prevented the increased severity of parkinsonian motor symptoms but was unable to
      maintain a reduced expression of dyskinesia with repeated administration. These
      data demonstrate the clinical utility of the modulation of the serotonergic and
      adenosine neurotransmitter systems with selective pharmacological agents for only
      acute treatment of LID. This multi-targeted approach is unsuitable as a long-term
      treatment regimen due to unsustainable therapeutic effects on dyskinesia.

PMID- 28739087
TI  - Inhibition of lipolysis by ilexgenin A via AMPK activation contributes to the
      prevention of hepatic insulin resistance.
AB  - Adipose dysfunction links tightly to hepatic insulin resistance and
      gluconeogenesis. Ilexgenin A is reported with the ability to regulate lipid
      profile and protect the liver against high fat diet (HFD) -induced impairment.
      Here, we propose that ilexgenin A ameliorates hepatic insulin signaling and
      gluconeogenesis by regulating lipolysis in white adipose tissue (WAT). Pyruvate
      tolerance test and biochemical analysis coupled with the ex vivo siRNA knockdown
      and co-culture studies demonstrate that ilexgenin A suppresses inflammation
      associated lipolysis in epididymal fat pad via 5'-AMP-activated protein kinase
      (AMPK) activation, thus inhibits diacylglycerol (DAG) accumulation and protein
      kinase C epsilon (PKCepsilon) translocation in liver, leading to the improvement
      of insulin sensitivity and hepatic glucose production. These findings suggest
      that the relationship between adipose function and hepatic insulin action may be
      targeted by natural bioactive components for the potential treatment of hepatic
      insulin resistance related disorders.

PMID- 28739088
TI  - Trimucrin, an Arg-Gly-Asp containing disintegrin, attenuates myocardial ischemia
      reperfusion injury in murine by inhibiting platelet function.
AB  - Trimucrin, a novel small-mass Arg-Gly-Asp (RGD)-containing disintegrin, has been
      demonstrated to possess anti-platelet and anti-inflammatory effect through
      blockade of platelet alphaIIbbeta3 and phagocyte alphavbeta3 integrin. In this
      study, we found that the platelet-rich plasma prepared from trimucrin-treated
      rats platelet aggregation was diminished in response to adenosine diphosphate
      (ADP). We tried to determine whether trimucrin is cardioprotective in rats
      subjected to myocardial ischemia-reperfusion (I-R) injury. The left anterior
      descending coronary artery of anesthetized rats was subjected to 1h occlusion and
      3h reperfusion. The animals received intravenous trimucrin or saline, and the
      severities of I-R-induced arrhythmia and infarction were compared. Trimucrin
      significantly reduced I-R-induced arrhythmias and reduced mortality, as well as
      infarct volume, troponin-I levels, creatine kinase, and lactate dehydrogenase
      activity in carotid blood compared with vehicle-treated animals during the same
      period. Trimucrin also improved cardiac function and survival rates after I-R
      injury. In addition, trimucrin concentration-dependently inhibited platelet
      adhesion on collagen- and fibrinogen-coated surfaces without affecting platelet
      counts. Trimucrin also significantly reduced neutrophil infiltration into heart
      tissues after I-R compared with controls. Furthermore, trimucrin treatment caused
      significant downregulation of Bax, Caspase-3 apoptotic proteins and upregulation
      of anti-apoptotic Bcl-2 protein. These results demonstrate that trimucrin exerts
      cardioprotective property against myocardial I-R injury mediated through
      antiplatele, anti-inflammatory, anti-apoptotic mechanism, as well as improvements
      in cardiac function.

PMID- 28739089
TI  - The Feulgen reaction: A brief review and new perspectives.
AB  - The Feulgen reaction has been proposed by Robert Feulgen and Heinrich Rossenbeck
      for the identification of DNA nearly a hundred years ago. Since then, many other
      applications of this cytochemical/topochemical procedure at qualitative and
      quantitative level have been proposed in relation to DNA and its role in
      chromatin in human, animal and plant cells. In this article, we briefly review
      some fundamental aspects of the Feulgen reaction and current applications of such
      a method in studies of altered chromatin texture, including its association with
      or preceding changes in transcriptional activities and effect on epigenetic
      marks. Further perspectives on the use of the Feulgen reaction will depend of the
      proposal of innovative biological questions in which its reveals appropriate.

PMID- 28739090
TI  - Prognostic power of circumferential resection margin in patients with esophageal
      cancer deserves additional investigation.

PMID- 28739091
TI  - Laparoscopic sleeve gastrectomy: Effect on long-term remission for morbidly obese
      patients with type 2 diabetes at 5-year follow up.
AB  - BACKGROUND: In the short-term, laparoscopic sleeve gastrectomy has been shown to
      be effective for the treatment of the type 2 diabetes in patients with severe
      obesity. There are few data with greater follow-up. Our aim was to evaluate the
      results of laparoscopic sleeve gastrectomy on the control of type 2 diabetes in
      patients with severe obesity at 5 years at the University Hospital, France.
      METHODS: From a total of 355 patients with severe obesity operated between
      January 2006 and June 2010, 52 (15%) had a diagnosis of type 2 diabetes before
      undergoing laparoscopic sleeve gastrectomy. RESULTS: There were 31 females (60%)
      and 21 males (40%), with a mean age of 51 +/- 10 years (range 27-67) with a mean
      body mass index of 48 +/- 10 kg/m2 (range 35-82). The mean duration of type 2
      diabetes was 10.8 +/- 10.8 years before bariatric operation. The preoperative
      glycated hemoglobin was 8 +/- 2% (range 5.9-12.8) in 45 patients; 17 patients
      (38%) had levels of glycated hemoglobin >=9%. Three patients (6%) required
      insulin alone, 4 (8%) were taking oral antidiabetic medicine and insulin, and the
      remaining 45 patients (87%) were taking only oral antidiabetic medicines. The
      complete data regarding weight loss at 5-year follow-up were obtained for 46
      patients, yielding an overall follow-up rate of 89%. The prolonged remission of
      type 2 diabetes achieved at 1 year that persisted at 5 years of follow-up was
      present in 9 patients (17%). No patient with complete remission of their type 2
      diabetes required insulin preoperatively. Improvement of type 2 diabetes was
      observed in 30 patients (58%) at 1 year, which was maintained for 27 patients
      (52%) at 5-year follow-up. CONCLUSION: Laparoscopic sleeve gastrectomy has
      demonstrated a moderate efficacy in the treatment morbidly obese patients with
      type 2 diabetes. Markedly increased preoperative glycated hemoglobin levels,
      older age, and preoperative need for insulin treatment may be the factors
      predicting failure of complete remission of type 2 diabetes after laparoscopic
      sleeve gastrectomy.

PMID- 28739092
TI  - Numeric pathologic lymph node classification shows prognostic superiority to
      topographic pN classification in esophageal squamous cell carcinoma.
AB  - BACKGROUND: The current eighth tumor node metastasis lymph node category
      pathologic lymph node staging system for esophageal squamous cell carcinoma is
      based solely on the number of metastatic nodes and does not consider anatomic
      distribution. We aimed to assess the prognostic capability of the eighth tumor
      node metastasis pathologic lymph node staging system (numeric-based) compared
      with the 11th Japan Esophageal Society (topography-based) pathologic lymph node
      staging system in patients with esophageal squamous cell carcinoma. METHODS: We
      retrospectively reviewed the clinical records of 289 patients with esophageal
      squamous cell carcinoma who underwent esophagectomy with extended lymph node
      dissection during the period from January 2006 through June 2016. We compared
      discrimination abilities for overall survival, recurrence-free survival, and
      cancer-specific survival between these 2 staging systems using C-statistics.
      RESULTS: The median number of dissected and metastatic nodes was 61 (25% to 75%
      quartile range, 45 to 79) and 1 (25% to 75% quartile range, 0 to 3),
      respectively. The eighth tumor node metastasis pathologic lymph node staging
      system had a greater ability to accurately determine overall survival (C
      statistics: tumor node metastasis classification, 0.69, 95% confidence interval,
      0.62-0.76; Japan Esophageal Society classification; 0.65, 95% confidence
      interval, 0.58-0.71; P = .014) and cancer-specific survival (C-statistics: tumor
      node metastasis classification, 0.78, 95% confidence interval, 0.70-0.87; Japan
      Esophageal Society classification; 0.72, 95% confidence interval, 0.64-0.80; P =
      .018). Rates of total recurrence rose as the eighth tumor node metastasis
      pathologic lymph node stage increased, while stratification of patients according
      to the topography-based node classification system was not feasible. CONCLUSION:
      Numeric nodal staging is an essential tool for stratifying the oncologic outcomes
      of patients with esophageal squamous cell carcinoma even in the cohort in which
      adequate numbers of lymph nodes were harvested.

PMID- 28739093
TI  - Individual surgeon is an independent risk factor for leak after double-stapled
      colorectal anastomosis: An institutional analysis of 800 patients.
AB  - BACKGROUND: Our aim was to assess whether the individual surgeon is an
      independent risk factor for anastomotic leak in double-stapled colorectal
      anastomosis after left colon and rectal cancer resection. METHODS: This
      retrospective analysis of a prospectively collected database consists of a
      consecutive series of 800 patients who underwent an elective left colon and
      rectal resection with a colorectal, double-stapled anastomosis between 1993 and
      2009 in a specialized colorectal unit of a tertiary hospital with 7 participating
      surgeons. The main outcome variable was anastomotic leak, defined as leak of
      luminal contents from a colorectal anastomosis between 2 hollow viscera diagnosed
      radiologically, clinically, endoscopically, or intraoperatively. Pelvic abscesses
      were also considered to be an anastomotic leak. Radiologic examination was
      performed when there was clinical suspicion of leak. RESULTS: Anastomotic leak
      occurred in 6.1% of patients, of which 33 (67%) were treated operatively, 6 (12%)
      with radiologic drains, and 10 (21%) by medical treatment. Postoperative
      mortality rate was 2.9% for the whole group of 800 patients. In patients with
      anastomotic leak, mortality rate increased up to 16% vs 2.0% in patients without
      anastomotic leak (P < .0001). At multivariate analysis, rectal location of tumor,
      male sex, bowel obstruction preoperatively, tobacco use, diabetes, perioperative
      transfusion, and the individual surgeon were independent risk factors for
      anastomotic leak. The surgeon was the most important factor (mean odds ratio 4.9;
      range 1.0 to 13.5). The variance of anastomotic leak between the different
      surgeons was 0.56 in the logit scale. CONCLUSION: The individual surgeon is an
      independent risk factor for leakage in double-stapled, colorectal, end-to-end
      anastomosis after oncologic left-sided colorectal resection.

PMID- 28739094
TI  - Automatic repositioning of jaw segments for three-dimensional virtual treatment
      planning of orthognathic surgery.
AB  - PURPOSE: To develop a computer-based method for automating the repositioning of
      jaw segments in the skull during three-dimensional virtual treatment planning of
      orthognathic surgery. The method speeds up the planning phase of the orthognathic
      procedure, releasing surgeons from laborious and time-consuming tasks. MATERIALS
      AND METHODS: The method finds the optimal positions for the maxilla, mandibular
      body, and bony chin in the skull. Minimization of cephalometric differences
      between measured and standard values is considered. Cone-beam computed
      tomographic images acquired from four preoperative patients with skeletal
      malocclusion were used for evaluating the method. RESULTS: Dentofacial problems
      of the four patients were rectified, including skeletal malocclusion, facial
      asymmetry, and jaw discrepancies. CONCLUSIONS: The results show that the method
      is potentially able to be used in routine clinical practice as support for
      treatment-planning decisions in orthognathic surgery.

PMID- 28739095
TI  - The Rapidly Evolving Landscape of Bariatric Surgery.

PMID- 28739096
TI  - A Canadian and Historical Perspective on Bariatric Surgery.

PMID- 28739097
TI  - Surgery for Diabetes: Clinical and Mechanistic Aspects.
AB  - According to the most recent publication by the Canadian Public Health Agency,
      obesity affects 25% of adults. In addition, there is a clear association between
      the recent rise in obesity and the increased prevalence of type 2 diabetes.
      Medical therapy for obesity has shown limited long-term effectiveness, and
      surgical treatment is now recognized by medical authorities as part of the
      armamentarium for the management of type 2 diabetes in severely obese patients.
      The current indications for obesity surgery and postoperative management are
      reviewed. The choice of surgery should balance expected benefits associated with
      weight loss (including remission rate of type 2 diabetes), side effects and the
      risks for early and long-term complications. Long-term outcomes of metabolic
      surgery for diabetes vary according to the type of surgery (ranging between 20%
      and 90% remission rates) and the underlying metabolic changes. Several controlled
      trials have been published in recent years confirming the superiority of
      metabolic surgery over medical treatment for the management of type 2 diabetes
      associated with severe obesity. Some of the known underlying mechanisms of action
      include a combination of caloric restriction, hormonal changes, decreased
      nutrient absorption and changes in bile acids, microbiota and incretins. Further
      research is needed to clarify the mechanistic changes associated with each
      surgical procedure and their respective long-term outcomes.

PMID- 28739098
TI  - Effects of Bariatric Surgery on Energy Homeostasis.
AB  - Bariatric surgery represents the most efficient therapy for severe obesity. It
      reduces the size of fat stores or the amount of body fat gain. The bariatric
      surgery procedures currently used include Roux-en-Y gastric bypass and sleeve
      gastrectomy, which are the most commonly performed procedures. Other procedures
      are laparoscopic adjustable gastric banding and biliopancreatic diversion. The
      latter represents the most effective surgery for treatment of severe obesity as
      well as type 2 diabetes. Bariatric surgery reduces energy intake by restricting
      the size of the stomach reservoir and causing malabsorption, as in the case of
      biliopancreatic diversion. The present article provides an overview of the
      literature on the effects of bariatric surgery on energy homeostasis. Accumulated
      evidence has indicated that the effects of bariatric surgery on energy balance
      can encompass complex components including effects on the corticolimbic
      appetitive network, with modulatory effects exerted through changes in
      gastrointestinal hormones, bile acid production and microbiota composition. The
      reorganization of the gastrointestinal tract has been shown to reduce the
      rewarding effects of palatable food and impulsive eating, while elevating
      anorexigenic hormones glucagon-like peptide 1 and peptide tyrosine tyrosine to
      stimulate the production of bile acids and normalize the obesogenic gut
      microbiota. Bariatric surgery could also increase energy expenditure, which
      represents, like energy intake, a key component of the energy balance equation.

PMID- 28739099
TI  - Changes of meibomian glands in the early stage of post hematopoietic stem cell
      transplantation.
AB  - Hematopoietic stem cell transplantation (HSCT) is the most effective cure for
      hematologic malignancies. Graft-versus-host disease (GVHD) is a major
      complication following allogeneic HSCT, which significantly affects non-relapse
      mortality. And ocular manifestations of GVHD are known to occurin 60-90% of
      patients with chronic GVHD. Although the pathogenesis of ocular GVHD is not
      clearly known, it is known to progress into inflammation and fibrosis through
      presentation of antigens on CD4 and CD8 T cells. There is much evidence that the
      ocular surface and meibomian glands are severely damaged in ocular GVHD patients,
      and there are few observational studies on the early changes. In this review, we
      will discuss the various changes in the meibomian glands and ocular surface, and
      tear dynamics in the early stage following HSCT. These results show that tear
      film break-up time (TFBUT) decreased and the corneal staining score was
      significantly higher 2-3 months after HSCT. The upper eyelid and total eyelid
      meiboscore increased after 3 months following HSCT. The information of the early
      changes of meibomian glands morphology would be helpful to further examine the
      pathogenesis of meibomian gland dysfunction.

PMID- 28739100
TI  - Movement of retinal vessels toward the optic nerve head after increasing
      intraocular pressure in monkey eyes with experimental glaucoma.
AB  - A shift or displacement of the retinal blood vessels (RBVs) with neuroretinal rim
      thinning indicates the progression of glaucomatous optic neuropathy. In chronic
      open angle glaucoma, individuals with RBV positional shifts exhibit more rapid
      visual field loss than those without RBV shifts. The retinal vessels reportedly
      move onto the optic nerve head (ONH) in response to glaucoma damage, suggesting
      that RBVs are pulled toward the ONH in response to increased cupping. Whether
      this phenomenon only applies to RVBs located in the vicinity or inside the ONH
      or, more generally, to RBVs also located far from the ONH, however, is unclear.
      The aim of this study was to evaluate the movement of RBVs located relatively far
      from the ONH edge after increasing intraocular pressure (IOP) in an experimental
      monkey model of glaucoma. Fundus photographs were obtained in 17 monkeys. High
      IOP was induced in the monkeys by laser photocoagulation burns applied uniformly
      with 360 degrees  irradiation around the trabecular meshwork of the left eye. The
      right eye was left intact and used as a non-treated control. Considering the
      circadian rhythm of IOP, it was measured in both eyes of each animal at around
      the same time-points. Then, fundus photographs were obtained. Using Image J image
      analysis software, an examiner (N.E.) measured the fundus photographs at two time
      points, i.e. before laser treatment (time 1) and the last fundus photography
      after IOP elevation (time 2). The following parameters were measured (in pixels):
      1) vertical diameter of the ONH (DD), 2) distance from the ONH edge to the first
      bifurcation point of the superior branch of the central retinal vein (UV), 3)
      distance from the ONH edge to the first bifurcation point of the inferior branch
      of the central retinal vein (LV), 4) ONH area, and 5) surface area of the cup of
      the ONH. We calculated the ratios of UV to DD (UV/DD), LV to DD (LV/DD), and the
      cup area to disc area ratio (C/D). The mean UV/DD at time 1 (0.656 +/- 0.233) was
      decreased at time 2 (0.542 +/- 0.192) (p < 0.01), and the mean LV/DD at time 1
      (0.642 +/- 0.151) was decreased at time 2 (0.534 +/- 0.171) (p < 0.01). The mean
      C/D at time 1 (0.303 +/- 0.035) was increased at time 2 (0.556 +/- 0.110) (p <
      0.01). The mean IOP at time 1 was 19.8 +/- 2.5 and that at time 2 was 54.2 +/-
      15.8. The amount and rate of the change in LV/DD and C/D between time 1 and time
      2 were significantly correlated (r = -0.654 and -0.536, p = 0.004 and 0.026,
      respectively). Therefore, in an experimental monkey model of glaucoma, RBVs
      located relatively far from the ONH were pulled toward the ONH as cupping
      increased.

PMID- 28739101
TI  - Examining the effects of illicit drug use on tobacco cessation outcomes in the
      Helping HAND 2 randomized controlled trial.
AB  - BACKGROUND: Individuals with substance use disorders (SUD) smoke at higher rates
      and have higher tobacco-related mortality than the general population. Despite
      having an interest in smoking cessation, smokers with SUDs may have greater
      difficulty quitting. METHODS: Analysis of data from a RCT testing a post
      discharge smoking cessation intervention for hospitalized cigarette smokers
      interested in quitting. Past 7day tobacco abstinence was self-reported at 1, 3,
      and 6 months and biochemically confirmed at 6 months post-discharge. Other drug
      use was assessed at baseline by self-report or a past-year discharge diagnosis of
      SUD. Multiple logistic regression compared tobacco cessation outcomes among
      participants with no recreational drug use (NDU; n=942) vs. marijuana only (MU;
      n=284) vs. other illicit drugs (IDU; n=131). RESULTS: Groups differed at baseline
      on age, gender, race, education, other household smokers, alcohol use, and
      anxiety/depression (all p<0.05). Confirmed 6-month tobacco abstinence was lower
      among IDU than NDU participants (9% vs 18%, p=0.01; AOR=0.43, CI: 0.22-0.84)
      after adjustment for study arm, smoking characteristics, demographics, quality of
      life, alcohol use and MU. Confirmed 6-month abstinence did not differ
      significantly between MU vs. NDU participants (14% vs 18%, p>0.05; AOR=0.77,
      CI:0.51-1.14). Counseling and medication use did not differ significantly among
      groups at any follow-up. CONCLUSIONS: Hospitalized smokers who planned to stop
      smoking after discharge and used cessation assistance were less successful if
      they had used illicit drugs in the past year, but not if they had only used
      marijuana. More intensive or tailored interventions may be required to address
      smoking in this population.

PMID- 28739102
TI  - Microplastics in coastal environments of the Arabian Gulf.
AB  - Eight sandy beaches along the coastline of Qatar and four sea surface stations on
      the eastern coast, adjacent to Doha Bay, were surveyed between December 2014 and
      March 2015. Microplastics, mainly low density polyethylene and polypropylene,
      were found in all samples of sediments and seawater. Blue fibers, ranging between
      1 and 5mm, were the dominant type of particle present. Abundances on the sea
      surface varied between 4.38*104 and 1.46*106particles.km-2, with the highest
      values being consistently found 10km offshore, suggesting the presence of a
      convergence zone. No significant temporal variability was detected for sea
      surface samples. The concentration of microplastics in intertidal sediments
      varied between 36 and 228particlesm-2, with no significant differences among the
      8 beaches examined. These results show the pervasiveness of microplastic
      pollution in coastal environments of the Arabian Gulf. Potential local sources
      and sinks for microplastics are discussed.

PMID- 28739103
TI  - Contamination assessment of mercury, lead, cadmium and arsenic in surface
      sediments of Chabahar Bay.
AB  - This study aimed to investigate heavy metals content of mercury (Hg), lead (Pb),
      cadmium (Cd) and arsenic (As) in surface sediments of Chabahar Bay. Sediment
      samples were taken from 13 stations and then analyzed. The concentration of Hg,
      Pb, Cd and As ranged between 0.06 and 0.14ppm, 8 and 23ppm, 0.05 and 0.9ppm and 5
      and 22ppm, respectively. Arsenic content was more than ERL at some stations.
      Statistical analyses indicated critical importance of organic matter and mud in
      metal dispersion. Also, positive correlation of Al with Pb, Hg and Cd probably
      implies their terrestrial origination. Average enrichment factor of Hg, Pb, Cd
      and As were 2.67+/-0.95, 0.77+/-0.28, 6.56+/-9.9, and 7.53+/-3.44, respectively.
      Most stations were classified as moderately polluted and non-polluted sites.

PMID- 28739104
TI  - Hepatic trace element concentrations of breeding female common eiders across a
      latitudinal gradient in the eastern Canadian Arctic.
AB  - We examined hepatic concentrations of arsenic (As), cadmium (Cd), copper (Cu),
      lead (Pb), manganese (Mn), mercury (Hg), rubidium (Rb), selenium (Se) and zinc
      (Zn) in 10 breeding female common eiders (Somateria mollissima) from each of
      three colonies across 20 degrees  of latitude. Levels of many elements were
      elevated in eiders, although generally below levels of toxicological concern. We
      found significant differences in concentrations of As, Rb, Hg, Mn and Se among
      colonies, but not in a consistent pattern with latitude, and Hg:Se molar ratios
      did not vary among colonies. Furthermore, overlap in element concentrations from
      birds at different colonies meant that we could not reliably differentiate birds
      from different colonies based on a suite of their hepatic trace element
      concentrations. We encourage other researchers to assess baseline trace element
      levels on this important, harvested species, as a means of tracking contamination
      of nearshore benthic environments in the circumpolar Arctic.

PMID- 28739105
TI  - Mountains to the sea: River study of plastic and non-plastic microfiber pollution
      in the northeast USA.
AB  - Aquatic environments are sinks for anthropogenic contamination, whether chemical
      or solid pollutants. Microfibers shed from clothing and other textiles contribute
      to this problem. These can be plastic or non-plastic origin. Our aim was to
      investigate the presence and distribution of both types of anthropogenic
      microfibers along the length of the Hudson River, USA. Surface grab samples were
      collected and filtered through a 0.45MUm filter paper. Abundance of fibers was
      determined after subtraction of potential contamination. 233 microfibers were
      recorded in 142 samples, averaging 0.98microfibersL-1. Subsequent micro-FTIR
      showed half of the fibers were plastic while the other half were non-plastic, but
      of anthropogenic origin. There was no relationship between fiber abundance,
      wastewater treatment plant location or population density. Extrapolating from
      this data, and using available hydrographic data, 34.4% of the Hudson River's
      watershed drainage area contributes an average 300 million anthropogenic
      microfibers into the Atlantic Ocean per day.

PMID- 28739106
TI  - Drilling discharges reduce sediment reworking of two benthic species.
AB  - Effects of water-based drill cuttings on sediment reworking activity were studied
      on two important benthic bioturbators (the bivalve Abra segmentum and the brittle
      star Amphiura filiformis) using thin aquaria, fluorescent-dyed sediment particles
      (luminophores), time lapse photography and image analysis. In the present
      context, sediment reworking activity was measured as maximum mixing depth and
      total amount of luminophores transported below the sediment-water interface.
      There was a significant reduction in the amount of downward transported
      luminophores in drill cuttings treatments compared to controls with added natural
      sediments for both species, which also was true regarding maximum mixing depth
      for A. segmentum. Further, A. filiformis showed a clearly delayed burrowing of
      luminophores in the drill cuttings treatment compared to control. To conclude,
      the study showed that water-based drill cuttings have the potential to reduce
      sediment reworking. Further, it is evidenced that water-based drill cuttings not
      only cause burial effects.

PMID- 28739107
TI  - Hydrostatic pressure and the experimental toxicology of marine fishes: The
      elephant in the room.
AB  - Hydrostatic pressure (HP) increases linearly with depth in aquatic environments,
      so that many fish species routinely experience moderate-to-high HP levels (i.e.,
      from a few to dozens of MPa). Biological effects of this thermodynamic variable
      are evidenced by a reduced functionality of many biomolecular systems, even in
      barotolerant and barophilic species. It is likely that environmentally-relevant
      HP levels (i.e., above atmospheric) could also modulate the responsiveness to and
      toxic effects of pollutants in fish. Still, only a few laboratories have
      investigated this possibility. The already-published ecobarotoxicological studies
      have brought strong support to the notion that HP can indeed modulate pollutant
      response in shallow-water and deep-sea animals. A careful reassessment of
      toxicity responses is therefore required. To quantify the exact influence of HP
      in marine fish toxicology, a research framework is proposed that should ensure
      the collection of meaningful data for risk assessment, using standard toxicity
      testing and mechanistic approaches.

PMID- 28739108
TI  - Use of cis-atracurium to maintain moderate neuromuscular blockade in experimental
      pigs.
AB  - OBJECTIVE: To determine the dose of cis-atracurium needed to produce a moderate
      neuromuscular blockade (NMB) in pigs. STUDY DESIGN: Prospective experimental
      study. ANIMALS: Seven pigs [five females and two males; median (range) body
      weight: 47 (36-64) kg]. METHODS: Pigs were premedicated with intramuscular
      midazolam (0.3 mg kg-1) and ketamine (7 mg kg-1). Anaesthesia was induced with
      intravenous (IV) propofol 3 (1-4) mg kg-1 and maintained with isoflurane in
      oxygen. Based on a preliminary study, the subjects were administered 0.3 mg kg-1
      cis-atracurium followed by 0.48 mg kg-1 hour-1 constant rate infusion (CRI) IV. A
      moderate NMB was defined as a train-of-four (TOF) count of <=2 by
      acceleromyography. When the TOF count was >2, 0.1 mg kg-1 cis-atracurium was
      administered and the CRI was increased. The cis-atracurium CRI was decreased when
      the TOF count was under 2 for more than 15 minutes. The total dose of cis
      atracurium required to maintain a moderate NMB was calculated as the total amount
      of cis-atracurium used (both CRI and supplementary boluses) divided by the
      administration time. RESULTS: The cis-atracurium CRI lasted for 87 (76-151)
      minutes. To induce and maintain a moderate neuromuscular blockade, the initial
      dose of cis-atracurium was 0.3 (0.3- 0.5) mg kg-1 and the CRI was 0.71 (0.37
      0.98) mg kg-1 hour-1. CONCLUSIONS AND CLINICAL RELEVANCE: The doses described in
      our study may help researchers obtain a moderate NMB using cis-atracurium in
      pigs.

PMID- 28739109
TI  - Generation of glucose-sensitive insulin-secreting beta-like cells from human
      embryonic stem cells by incorporating a synthetic lineage-control network.
AB  - We previously reported novel technology to differentiate induced pluripotent stem
      cells (IPSCs) into glucose-sensitive insulin-secreting beta-like cells by
      engineering a synthetic lineage-control network regulated by the licensed food
      additive vanillic acid. This genetic network was able to program intricate
      expression dynamics of the key transcription factors Ngn3 (neurogenin 3, OFF-ON
      OFF), Pdx1 (pancreatic and duodenal homeobox 1, ON-OFF-ON) and MafA (V-maf
      musculoaponeurotic fibrosarcoma oncogene homologue A, OFF-ON) to guide the
      differentiation of IPSC-derived pancreatic progenitor cells to beta-like cells.
      In the present study, we show for the first time that this network can also
      program the expression dynamics of Ngn3, Pdx1 and MafA in human embryonic stem
      cell (hESC)-derived pancreatic progenitor cells and drive differentiation of
      these cells into glucose-sensitive insulin-secreting beta-like cells. Therefore,
      synthetic lineage-control networks appear to be a robust methodology for
      differentiating pluripotent stem cells into somatic cell types for basic research
      and regenerative medicine.

PMID- 28739110
TI  - Transforming Growth Factor Beta1 being considered a novel biomarker in knee
      osteoarthritis.
AB  - BACKGROUND: Associations between Transforming Growth Factor beta-1 (TGF-beta1),
      Platelet-derived growth factor BB (PDGF-BB) and C-terminal telopeptide of type I
      collagen (CTX-1) with pathogenesis of osteoarthritis (OA) have already been
      established. Therefore, TGF-beta1, PDGF-BB and CTX-1 could be used as the
      potential biomarkers for the diagnosis of this disease. METHODS: 160 knee OA
      cases and 80 healthy controls were chosen. Serum concentrations of TGF-beta1,
      PDGF-BB and CTX-1 were tested twice on the same samples using Enzyme-Linked
      Immunosorbent Assay. Knee OA cases were classified using Kellgren-Lawrence (K-L)
      criteria into four groups. Western Ontario and McMaster Universities (WOMAC)
      Osteoarthritis Index scores were evaluated for all cases. RESULTS: TGF-beta1
      serum levels in knee OA cases were significantly higher compared to controls
      (t=11.37, p<0.01). Average serum level of TGF-beta1 was positively associated
      with K-L grades. The diagnostic efficiency of serum TGF-beta1 was proved to be
      moderate and the cut-point value was 12.11ng/ml showing favorable diagnostic
      indexes. In contrast, similarities were found not only in serum levels of PDGF-BB
      and CTX-1 between OA groups and controls but also in WOMAC scores. CONCLUSION:
      Our findings supported that TGF-beta1 has a positive correlation with the
      severity of knee OA confirmed by radiographs. Therefore, TGF-beta1 might serve as
      a potential biomarker in established knee OA.

PMID- 28739111
TI  - Reply to: "How to better predict microvascular invasion and recurrence of
      hepatocellular carcinoma".

PMID- 28739112
TI  - Reactivation of hepatitis B virus from an isolated anti-HBc positive patient
      after eradication of hepatitis C virus with direct-acting antiviral agents.

PMID- 28739113
TI  - Anterior Cervical Osteophyte Presenting as a Pharyngeal Mass.

PMID- 28739114
TI  - Ethical and medical management of a pregnant woman with brain stem death
      resulting in delivery of a healthy child and organ donation.
AB  - Maternal brain death during pregnancy remains an exceedingly complex situation
      that requires not only a well-considered medical management plan, but also
      careful decision-making in a legally and ethically delicate situation. Management
      of brain dead pregnant patients needs to adhere to special strategies that
      support the mother in a way that she can deliver a viable and healthy child.
      Brain death in pregnant women is very rare, with only a few published cases. We
      present a case of a pregnant woman with previously diagnosed multiple brain
      cavernomas that led to intracranial hemorrhage and brain stem death during the
      21st week of pregnancy. The condition that can be proven unequivocally, using
      tests that do not endanger viability of the fetus, is brain stem death, diagnosed
      through absence of cranial reflexes. The patient was successfully treated until
      delivery of a healthy female child at 29weeks of gestation. The patient received
      continuous hormone substitution therapy, fetal monitoring and extrinsic
      regulation of maternal homeostasis over 64days. After delivery, the final
      diagnosis of brain death was established through multi-slice computerized
      tomography pan-angiography. This challenging case discusses ethical and medical
      circumstances arising from a diagnosis of maternal brain death, while showing
      that prolongation of somatic life support in a multidisciplinary setting can
      result in a successful pregnancy outcome.

PMID- 28739115
TI  - A recombinant protein of Salmonella Typhi induces humoral and cell-mediated
      immune responses including memory responses.
AB  - Gram negative enteric bacteria, Salmonella enterica serovar Typhi (S. Typhi), the
      etiological agent of typhoid fever is a major public health problem in developing
      countries. While a permanent solution to the problem would require improved
      sanitation, food and water hygiene, controlling the infection by vaccination is
      urgently required due to the emergence of multidrug resistant strains in multiple
      countries. The currently licensed vaccines are moderately efficacious with
      limited applicability, and no recommended vaccines exist for younger children. We
      had previously reported that a candidate vaccine based on recombinant outer
      membrane protein (rT2544) of S. Typhi is highly immunogenic and protective in
      mice. Here we show that rT2544-specific antiserum is capable of mediating
      bacterial lysis by the splenocytes through Antibody-Dependent Cellular
      Cytotoxicity (ADCC). Increased populations of rT2544-specific IgA and IgG
      secreting plasma cells are found in the spleen, mesenteric lymph nodes and
      peyer's patches. Cell-Mediated Immune Responses (CMIR) induced by rT2544 consist
      of Th1 cell differentiation and generation of cytotoxic T lymphocytes (CTL),
      which produce IFN-gamma and are capable of destroying cells displaying T2544
      derived antigens. rT2544 elicits pro-inflammatory cytokines (TNF-alpha, IL-6)
      from Bone Marrow-Derived Dendritic cells (BMDCs), while in vitro re-stimulation
      of rT2544-primed CD4+ T cells induces cell proliferation and generates higher
      amounts of Th1 cytokines, such as IFN-gamma, TNF-alpha and IL-2. Finally, the
      candidate vaccine induces immunological memory in the form of memory B and T
      lymphocytes. Taken together, the study further supports the potential of rT2544
      as a novel and improved vaccine candidate against S. Typhi.

PMID- 28739116
TI  - Pneumococcal conjugate vaccine induced IgG and nasopharyngeal carriage of
      pneumococci: Hyporesponsiveness and immune correlates of protection for carriage.
AB  - BACKGROUND: Prior studies have demonstrated hyporesponsiveness to pneumococcal
      conjugate vaccines (PCVs) when administered in the presence of homologous
      carriage. This may be substantially more important in Africa where carriage
      prevalence is high. Deriving a correlate of protection (CoP) for carriage is
      important in guiding the future use of extended PCVs as population control of
      pneumococcal disease by vaccination is now focused principally on its indirect
      effect. We therefore explored the complex relationship between existing carriage
      and vaccine responsiveness, and between serum IgG levels and risk of acquisition.
      METHODS: We undertook secondary analyses of data from two previously published
      clinical trials of the safety and immunogenicity of PCV in Kenya. We compared
      responses to vaccination between serotype-specific carriers and non-carriers at
      vaccination. We assessed the risk of carriage acquisition in relation to PCV
      induced serum IgG levels using either a step- or continuous-risk function.
      RESULTS: For newborns, the immune response among carriers was 51-82% lower than
      that among non-carriers, depending on serotype. Among toddlers, for serotypes 6B,
      14 and 19F the post-vaccination response among carriers was lower by between 29
      and 70%. The estimated CoP against acquisition ranged from 0.26 to 1.93MUg/mL
      across serotypes, however, these thresholds could not be distinguished
      statistically from a model with constant probability of carriage independent of
      assay value. CONCLUSION: We have confirmed hyporesponsiveness in an equatorial
      African setting in both infants and toddlers. Population responses to vaccination
      are likely to improve with time as carriage prevalence of vaccine serotypes is
      reduced. We have not found clear correlates of protection against carriage
      acquisition among toddlers in this population. Assessing the potential of new
      vaccines through the use of CoP against carriage is still difficult as there are
      no clear-cut serotype specific correlates.

PMID- 28739117
TI  - Update on fertility preservation from the Barcelona International Society for
      Fertility Preservation-ESHRE-ASRM 2015 expert meeting: indications, results and
      future perspectives.
AB  - STUDY QUESTION: What progress has been made in fertility preservation (FP) over
      the last decade? SUMMARY ANSWER: FP techniques have been widely adopted over the
      last decade and therefore the establishment of international registries on their
      short- and long-term outcomes is strongly recommended. WHAT IS KNOWN ALREADY: FP
      is a fundamental issue for both males and females whose future fertility may be
      compromised. Reproductive capacity may be seriously affected by age, different
      medical conditions and also by treatments, especially those with gonadal
      toxicity. There is general consensus on the need to provide counselling about
      currently available FP options to all individuals wishing to preserve their
      fertility. STUDY DESIGN, SIZE, DURATION: An international meeting with
      representatives from expert scientific societies involved in FP was held in
      Barcelona, Spain, in June 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty
      international FP experts belonging to the American Society of Reproductive
      Medicine, ESHRE and the International Society of Fertility Preservation reviewed
      the literature up to June 2015 to be discussed at the meeting, and approved the
      final manuscript. At the time this manuscript was being written, new evidence
      considered relevant for the debated topics was published, and was consequently
      included. MAIN RESULTS AND THE ROLE OF CHANCE: Several oncological and non
      oncological diseases may affect current or future fertility, either caused by the
      disease itself or the gonadotoxic treatment, and need an adequate FP approach.
      Women wishing to postpone maternity and transgender individuals before starting
      hormone therapy or undergoing surgery to remove/alter their reproductive organs
      should also be counselled accordingly. Embryo and oocyte cryopreservation are
      first-line FP methods in postpubertal women. Metaphase II oocyte cryopreservation
      (vitrification) is the preferred option. Cumulative evidence of restoration of
      ovarian function and spontaneous pregnancies after ART following orthotopic
      transplantation of cryopreserved ovarian tissue supports its future consideration
      as an open clinical application. Semen cryopreservation is the only established
      method for FP in men. Testicular tissue cryopreservation should be recommended in
      pre-pubertal boys even though fertility restoration strategies by
      autotransplantation of cryopreserved testicular tissue have not yet been tested
      for safe clinical use in humans. The establishment of international registries on
      the short- and long-term outcomes of FP techniques is strongly recommended.
      LIMITATIONS, REASONS FOR CAUTION: Given the lack of studies in large cohorts or
      with a randomized design, the level of evidence for most of the evidence reviewed
      was 3 or below. WIDER IMPLICATIONS OF THE FINDINGS: Further high quality studies
      are needed to study the long-term outcomes of FP techniques. STUDY
      FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

PMID- 28739118
TI  - Single cell-based automated quantification of therapy responses of invasive
      cancer spheroids in organotypic 3D culture.
AB  - Organotypic in vitro culture of 3D spheroids in an extracellular matrix represent
      a promising cancer therapy prediction model for personalized medicine screens due
      to their controlled experimental conditions and physiological similarities to in
      vivo conditions. As in tumors in vivo, 3D invasion cultures identify intratumor
      heterogeneity of growth, invasion and apoptosis induction by cytotoxic therapy.
      We here combine in vitro 3D spheroid invasion culture with irradiation and
      automated nucleus-based segmentation for single cell analysis to quantify growth,
      survival, apoptosis and invasion response during experimental radiation therapy.
      As output, multi-parameter histogram-based representations deliver an integrated
      insight into therapy response and resistance. This workflow may be suited for
      high-throughput screening and identification of invasive and therapy-resistant
      tumor sub-populations.

PMID- 28739120
TI  - Detecting stable individual differences in the functional organization of the
      human basal ganglia.
AB  - Moving from group level to individual level functional parcellation maps is a
      critical step for developing a rich understanding of the links between individual
      variation in functional network architecture and cognitive and clinical
      phenotypes. Still, the identification of functional units in the brain based on
      intrinsic functional connectivity and its dynamic variations between and within
      subjects remains challenging. Recently, the bootstrap analysis of stable clusters
      (BASC) framework was developed to quantify the stability of functional brain
      networks both across and within subjects. This multi-level approach utilizes
      bootstrap resampling for both individual and group-level clustering to delineate
      functional units based on their consistency across and within subjects, while
      providing a measure of their stability. Here, we optimized the BASC framework for
      functional parcellation of the basal ganglia by investigating a variety of
      clustering algorithms and similarity measures. Reproducibility and test-retest
      reliability were computed to validate this analytic framework as a tool to
      describe inter-individual differences in the stability of functional networks.
      The functional parcellation revealed by stable clusters replicated previous
      divisions found in the basal ganglia based on intrinsic functional connectivity.
      While we found moderate to high reproducibility, test-retest reliability was high
      at the boundaries of the functional units as well as within their cores. This is
      interesting because the boundaries between functional networks have been shown to
      explain most individual phenotypic variability. The current study provides
      evidence for the consistency of the parcellation of the basal ganglia, and
      provides the first group level parcellation built from individual-level cluster
      solutions. These novel results demonstrate the utility of BASC for quantifying
      inter-individual differences in the functional organization of brain regions, and
      encourage usage in future studies.

PMID- 28739119
TI  - Structural and functional, empirical and modeled connectivity in the cerebral
      cortex of the rat.
AB  - Connectomics data from animal models provide an invaluable opportunity to reveal
      the complex interplay between structure and function in the mammalian brain. In
      this work, we investigate the relationship between structural and functional
      connectivity in the rat brain cortex using a directed anatomical network
      generated from a carefully curated meta-analysis of published tracing data, along
      with resting-state functional MRI data obtained from a group of 14 anesthetized
      Wistar rats. We found a high correspondence between the strength of functional
      connections, measured as blood oxygen level dependent (BOLD) signal correlations
      between cortical regions, and the weight of the corresponding anatomical links in
      the connectome graph (maximum Spearman rank-order correlation rho=0.48). At the
      network-level, regions belonging to the same functionally defined community tend
      to form more mutual weighted connections between each other compared to regions
      located in different communities. We further found that functional communities in
      resting-state networks are enriched in densely connected anatomical motifs.
      Importantly, these higher-order structural subgraphs cannot be explained by lower
      order topological properties, suggesting that dense structural patterns support
      functional associations in the resting brain. Simulations of brain-wide resting
      state activity based on neural mass models implemented on the empirical rat
      anatomical connectome demonstrated high correlation between the simulated and the
      measured functional connectivity (maximum Pearson correlation rho=0.53), further
      suggesting that the topology of structural connections plays an important role in
      shaping functional cortical networks.

PMID- 28739121
TI  - Risk factors for conversion of laparoscopic cholecystectomy to open surgery - A
      systematic literature review of 30 studies.
AB  - BACKGROUND: The study aims to evaluate the methodological quality of publications
      relating to predicting the need of conversion from laparoscopic to open
      cholecystectomy and to describe identified prognostic factors. METHOD: Only
      English full-text articles with their own unique observations from more than 300
      patients were included. Only data using multivariate analysis of risk factors
      were selected. Quality assessment criteria stratifying the risk of bias were
      constructed and applied. RESULTS: The methodological quality of the studies were
      mostly heterogeneous. Most studies performed well in half of the quality criteria
      and considered similar risk factors, such as male gender and old age, as
      significant. Several studies developed prediction models for risk of conversion.
      Independent risk factors appeared to have additive effects. CONCLUSION: A
      detailed critical review of studies of prediction models and risk stratification
      for conversion from laparoscopic to open cholecystectomy is presented. One study
      is identified of high quality with a potential to be used in clinical practice,
      and external validation of this model is recommended.

PMID- 28739122
TI  - Idiopathic granulomatous mastitis: A diagnostic and therapeutic challenge.
AB  - BACKGROUND: Idiopathic granulomatous mastitis is a rare benign breast disease of
      women of reproductive age. It usually presents as a painful mass. Since the
      etiology is unclear, directed diagnosis and management is lacking. METHODS: This
      is a retrospective chart review of 14 patients, over twelve years (2004-2016),
      identified through query of pathology findings. RESULTS: Two asymptomatic
      patients were diagnosed after oncologic breast resection following neoadjuvant
      chemotherapy. The remaining twelve patients were young (31.7 years, range 23-43
      years), predominantly non-white (50% African/African-American, 36% Hispanic, 7%
      Asian), pregnant within the last five years (86%), with no prior granulomatous
      disease. Evaluation included breast imaging, microbial cultures and staining, and
      biopsy. Treatment included antibiotics (57%), corticosteroids (21%), methotrexate
      (7%), and/or surgery (71%). Imaging suggests segmental masses, possibly abscess.
      CONCLUSION: Granulomatous mastitis is uncommon, and difficult to diagnose and
      manage. We review our experience, the literature, and propose an algorithm for
      diagnosis and management.

PMID- 28739123
TI  - Effects of modifiable, non-modifiable and clinical process factors in ventral
      hernia repair surgical site infections: A retrospective study.
AB  - BACKGROUND: The hypothesis of this study is that non-modifiable factors are more
      important in ventral hernia repair (VHR) surgical site infection (SSI) than care
      process factors. METHODS: All VHR's which were reviewed retrospectively for both
      NSQIP-recorded data, and also: preoperative hospitalization, existing mesh,
      enterocutaneous fistula, open wound, case month, case day, case length,
      prophylactic antibiotics, skin preparation, other procedure performed, re-do
      operation, estimate blood loss, hernia size, repair approach, repair type, mesh
      used, skin closure, suture type, use of drains, and dressing. RESULTS: 7% of 223
      VHR's had an SSI. Factors associated with SSI: presence of mesh (24% vs. 4%),
      recurrent VHR (15% vs. 3%), operation time >120 min (15% vs. 3%), hernia size
      >200 cm2 (<25 cm2 2%, 26-200 cm2 4% and >200 cm2 11%), and EBL >100 ml (21% vs.
      3%). Other factors did not affect SSI rates. CONCLUSION: Factors associated with
      a more difficult operation were associated with SSI. Factors considered
      modifiable played limited roles. This has implications for choices of
      interventions made to reduce SSI rates.

PMID- 28739124
TI  - A Case for More Frequent, Not Just Earlier, Nephrology Care of Patients
      Approaching ESRD?

PMID- 28739125
TI  - Serum Uric Acid and Risk of Kidney Stones.

PMID- 28739126
TI  - Erratum Regarding "Acetazolamide and Hydrochlorothiazide Followed by Furosemide
      Versus Furosemide and Hydrochlorothiazide Followed by Furosemide for the
      Treatment of Adults With Nephrotic Edema: A Randomized Trial" (Am J Kidney Dis.
      2017;69[3]:420-427).

PMID- 28739127
TI  - Quiz: Nine Years of Persistent, Disabling Foot Pain in a Kidney Transplant
      Recipient.

PMID- 28739128
TI  - AJKD Atlas of Renal Pathology: Membranous Lupus Nephritis, ISN/RPS Class V.

PMID- 28739129
TI  - AJKD Atlas of Renal Pathology: Minimal Mesangial and Mesangial Proliferative
      Lupus Nephritis (ISN/RPS Class I and II).

PMID- 28739130
TI  - AJKD Atlas of Renal Pathology: Focal and Diffuse Lupus Nephritis (ISN/RPS Class
      III and IV).

PMID- 28739131
TI  - Ibudilast reduces oxaliplatin-induced tactile allodynia and cognitive impairments
      in rats.
AB  - Chemotherapy can cause serious neurotoxic side effects, such as painful
      peripheral neuropathies and disabling cognitive impairments. Four experiments
      examined whether Ibudilast, a clinically approved neuroimmune therapy, would
      reduce tactile allodynia and memory impairments caused by oxaliplatin in
      laboratory rats. Rats received an intraperitoneal injection of oxaliplatin
      (6mg/kg i.p.) or vehicle and were assessed for tactile allodynia 3 or 5days after
      injection, memory impairments in the novel object and novel location recognition
      tests 10-12days after injection, and fear conditioning 14days after injection.
      Ibudilast (7.5mg/kg) or vehicle was administered prior to oxaliplatin
      (Experiments 1 and 3) or prior to behavioural testing (Experiments 2 and 4).
      Ibudilast treatment prior to oxaliplatin prevented the development of tactile
      allodynia and memory impairments. Ibudilast treatment prior to behavioural
      testing reduced oxaliplatin-induced tactile allodynia, memory impairments, and
      impaired renewal of fear conditioning. These results suggest that Ibudilast could
      be an effective treatment against oxaliplatin-induced neuropathies and cognitive
      impairments.

PMID- 28739132
TI  - Colorimetric sensing of selenocystine using gold nanoparticles.
AB  - We present a highly selective and sensitive colorimetric method for the detection
      of selenocystine (SeCys) coexisting with other amino acids, especially cysteine
      (Cys) using the gold nanoparticles (AuNPs). Firstly, Cys was oxidized to cystine
      (Cys-Cys) by dissolved oxygen under Cu2+ catalysis in the pre-reaction, which
      eliminated the interference of Cys in the SeCys sensing process. Then SeCys
      induced the rapid aggregation of AuNPs through Au-Se bond and complex formation
      of Cu2+-SeCys in the colorimetric reaction, in which the color change of AuNPs
      from red to blue or purple with the naked eye detection or with a UV-vis
      spectrophotometric determination. The concentration of SeCys was quantified by
      the value at 670 nm from the second-derivative SPR absorbance spectrum. The
      linear range was from 2 MUM to 14 MUM with correlation coefficient of 0.999 and a
      detection limit (LOD) was 0.14 MUM. Moreover, the colorimetric response of AuNPs
      exhibited remarkable specificity to SeCys coexisting with 18 amino acids in a
      simulation sample, in which the total concentration of Cys and Cys-Cys was less
      than 15 MUM and the each concentration of other 16 common amino acids was 10 MUM.

PMID- 28739133
TI  - An enzyme-linked immunosorbent assay for the detection of diacetyl (2,3
      butanedione).
AB  - Diacetyl (2,3-butanedione) is an important metabolic marker of several cancers,
      as well as an important off-flavour component produced during fermentation. As a
      small molecule in a complex mixture with many other analytes, existing methods
      for identification and quantitation of diacetyl invariably involves a
      chromatographic separation step followed by signal integration with an
      appropriate stoichiometric detector. Here we demonstrate that the chemical
      reaction of diacetyl with a 1,2-phenylenediamine derivative yields a chemical
      adduct, 1,4-quinoxaline which can be conjugated on BSA. The BSA-diacetyl adduct
      can be used to select an adduct-specific monoclonal antibody in a Fab-format from
      a 45-billion member phage-display library. The availability of this antibody
      allowed the development of an enzyme-linked immunosorbent assay for diacetyl,
      based on the 1,4-quinoxaline competition for the antibodies with the diacetyl
      adduct immobilized on the plate. The described ELISA assay can detect the
      captured diacetyl in micromolar concentrations, both in water samples and in cell
      culture medium.

PMID- 28739134
TI  - NMDA receptor modulation by dextromethorphan and acute stress selectively alters
      electroencephalographic indicators of partial report processing.
AB  - Proceeding from a biophysical network model, the present study hypothesized that
      glutamatergic neurotransmission across the NMDA receptor (NMDAR) plays a key role
      in visual perception and its modulation by acute stress. To investigate these
      hypotheses, behavioral and electroencephalographic (EEG) indicators of partial
      report task processing were assessed in twenty-four healthy young men who
      randomly received a non-competitive NMDAR antagonist (0.8 mg/kg dextromethorphan,
      DXM) or a placebo, and concurrently accomplished a stress-induction (MAST) or
      control protocol in three consecutive sessions. Saliva samples served to quantify
      cortisol responses to the MAST, whereas a passive auditory oddball paradigm was
      implemented to verify the impact of DXM on the EEG-derived mismatch negativity
      component (MMN). DXM administration significantly increased MMN amplitudes but
      not salivary cortisol concentrations. By contrast, concurrent MAST exposure
      significantly reduced MMN latencies but also increased cortisol concentrations.
      With regard to EEG indicators, DXM administration reduced visually "evoked" (30Hz
      to 50Hz) and "induced" occipital gamma-band activity (70Hz to 100Hz), which was
      partly compensated by additional MAST exposure. However, neither the
      interventions nor EEG activity were significantly associated with behavioral
      partial report sensitivities. In summary, the present data suggest that
      glutamatergic neurotransmission across the NMDAR is only one among many
      determinants of intact visual perception. Accordingly, therapeutic doses of DXM
      and their inhibitory modulation by stress probably yield more pronounced
      electroencephalographic as compared with behavioural effects.

PMID- 28739135
TI  - Cytokinins in Symbiotic Nodulation: When, Where, What For?
AB  - Substantial progress has been made in the understanding of early stages of the
      symbiotic interaction between legume plants and rhizobium bacteria. Those include
      the specific recognition of symbiotic partners, the initiation of bacterial
      infection in root hair cells, and the inception of a specific organ in the root
      cortex, the nodule. Increasingly complex regulatory networks have been uncovered
      in which cytokinin (CK) phytohormones play essential roles in different aspects
      of early symbiotic stages. Intriguingly, these roles can be either positive or
      negative, cell autonomous or non-cell autonomous, and vary, depending on time,
      root tissues, and possibly legume species. Recent developments on CK symbiotic
      functions and interconnections with other signaling pathways during nodule
      initiation are the focus of this review.

PMID- 28739136
TI  - Coordinated tracking of linear multiagent systems with input saturation and
      stochastic disturbances.
AB  - This paper addresses the coordinated tracking problem for linear multiagent
      systems with input saturation and stochastic disturbances. The objective is to
      construct a class of tracking control laws that achieve consensus tracking in the
      absence of disturbances, while guaranteeing a bounded variance of the state
      difference between the follower agent and the leader in the present of
      disturbances, under the assumptions that each agent is asymptotically null
      controllable with bounded controls (ANCBC) and the network is connected. By using
      the low gain feedback technique, a class of tracking control algorithms are
      proposed, and the coordinated tracking problem is solved through some routine
      manipulations. Finally, numerical examples are provided to demonstrate the
      theoretical results.

PMID- 28739137
TI  - Corrigendum to "Epileptic feeling of multiple presences in the frontal space"
      [Cortex 46 (8) (2010) 1037-1042].

PMID- 28739138
TI  - The in-silico zebrafish matrisome: A new tool to study extracellular matrix gene
      and protein functions.
AB  - Extracellular matrix (ECM) proteins are major components of most tissues and
      organs. In addition to their crucial role in tissue cohesion and biomechanics,
      they chiefly regulate various important biological processes during embryonic
      development, tissue homeostasis and repair. In essence, ECM proteins were defined
      as secreted proteins that localized in the extracellular space. The
      characterization of the human and mouse matrisomes provided the first definition
      of ECM actors by comprehensively listing ECM proteins and classified them into
      categories. Because zebrafish is becoming a popular model to study ECM biology,
      we sought to characterize the zebrafish matrisome using an in-silico gene
      orthology-based approach. We report the identification of 1002 genes encoding the
      in-silico zebrafish matrisome. Using independent validations, we provide evidence
      for the robustness of the orthology-based approach. Moreover, we evaluated the
      orthology relationships between human and zebrafish genes at the whole-genome and
      matrisome levels and showed that the different categories of ECM genes are
      differentially subjected to evolutionary pressure. Last, we illustrate how the
      zebrafish matrisome list can be employed to annotate big data using the example
      of a previously published proteomic study of the skeletal ECM. The establishment
      of the zebrafish matrisome will undoubtedly facilitate the analysis of ECM
      components in "-omic" data sets.

PMID- 28739139
TI  - Results of the HEMO Study suggest that p-cresol sulfate and indoxyl sulfate are
      not associated with cardiovascular outcomes.
AB  - Cardiovascular disease, the leading cause of mortality in hemodialysis patients,
      is not fully explained by traditional risk factors. To help define non
      traditional risk factors, we determined the association of predialysis total p
      cresol sulfate, indoxyl sulfate, phenylacetylglutamine, and hippurate with
      cardiac death, sudden cardiac death, and first cardiovascular event in the 1,273
      participants of the HEMO Study. The results were adjusted for potential
      demographic, clinical, and laboratory confounders. The mean age of the patients
      was 58 years, 63% were Black and 42% were male. Overall, there was no association
      between the solutes and outcomes. However, in sub-group analyses, among patients
      with lower serum albumin (under 3.6 g/dl), a twofold higher p-cresol sulfate was
      significantly associated with a 12% higher risk of cardiac death (hazard ratio
      1.12; 95% confidence interval, 0.98-1.27) and 22% higher risk of sudden cardiac
      death (1.22, 1.06-1.41). Similar trends were also noted with indoxyl sulfate.
      Trial interventions did not modify the association between these solutes and
      outcomes. Routine clinical and lab data explained less than 22% of the
      variability in solute levels. Thus, in prevalent hemodialysis patients
      participating in a large U.S. hemodialysis trial, uremic solutes p-cresol
      sulfate, indoxyl sulfate, hippurate, and phenylacetylglutamine were not
      associated with cardiovascular outcomes. However, there were trends of toxicity
      among patients with lower serum albumin.

PMID- 28739140
TI  - The IL-4 receptor alpha has a critical role in bone marrow-derived fibroblast
      activation and renal fibrosis.
AB  - Renal fibrosis is a common pathway leading to the progression of chronic kidney
      disease, and bone marrow-derived fibroblasts contribute significantly to the
      development of renal fibrosis. However, the signaling mechanisms underlying the
      activation of these fibroblasts are not completely understood. Here, we examined
      the role of IL-4 receptor alpha (IL-4Ralpha) in the activation of myeloid
      fibroblasts in two experimental models of renal fibrosis. Compared with wild-type
      mice, IL-4Ralpha knockout mice accumulated fewer bone marrow-derived fibroblasts
      and myofibroblasts in their kidneys. IL-4Ralpha deficiency suppressed the
      expression of alpha-smooth muscle actin, extracellular matrix proteins and the
      development of renal fibrosis. Furthermore, IL-4Ralpha deficiency inhibited the
      activation of signal transducer and activator of transcription 6 (STAT6) in the
      kidney. Moreover, wild-type mice engrafted with bone marrow cells from IL-4Ralpha
      knockout mice exhibited fewer myeloid fibroblasts in the kidney and displayed
      less severe renal fibrosis following ureteral obstructive injury compared with
      wild-type mice engrafted with wild-type bone marrow cells. In vitro, IL-4
      activated STAT6 and stimulated expression of alpha-smooth muscle actin and
      fibronectin in mouse bone marrow monocytes. This was abolished in the absence of
      IL-4Ralpha. Thus, IL-4Ralpha plays an important role in bone marrow-derived
      fibroblast activation, resulting in extracellular matrix protein production and
      fibrosis development. Hence, the IL-4Ralpha/STAT6 signaling pathway may serve as
      a novel therapeutic target for chronic kidney disease.

PMID- 28739141
TI  - AMP-activated protein kinase/myocardin-related transcription factor-A signaling
      regulates fibroblast activation and renal fibrosis.
AB  - Chronic kidney disease is a major cause of death, and renal fibrosis is a common
      pathway leading to the progression of this disease. Although activated
      fibroblasts are responsible for the production of the extracellular matrix and
      the development of renal fibrosis, the molecular mechanisms underlying fibroblast
      activation are not fully defined. Here we examined the functional role of AMP
      activated protein kinase (AMPK) in the activation of fibroblasts and the
      development of renal fibrosis. AMPKalpha1 was induced in the kidney during the
      development of renal fibrosis. Mice with global or fibroblast-specific knockout
      of AMPKalpha1 exhibited fewer myofibroblasts, developed less fibrosis, and
      produced less extracellular matrix protein in the kidneys following unilateral
      ureteral obstruction or ischemia-reperfusion injury. Mechanistically, AMPKalpha1
      directly phosphorylated cofilin leading to cytoskeleton remodeling and myocardin
      related transcription factor-A nuclear translocation resulting in fibroblast
      activation and extracellular matrix protein production. Thus, AMPK may be a
      critical regulator of fibroblast activation through regulation of cytoskeleton
      dynamics and myocardin-related transcription factor-A nuclear translocation.
      Hence, AMPK signaling may represent a novel therapeutic target for fibrotic
      kidney disease.

PMID- 28739142
TI  - Radiation therapy for oligorecurrence in prostate cancer. Preliminary results of
      our centre.
AB  - INTRODUCTION AND OBJECTIVE: There is growing interest in the use of more
      aggressive therapeutic modalities for treating metastatic prostate cancer. In
      this study, we examine the use of stereotactic body radiation therapy (SBRT) for
      patients with oligorecurrent prostate cancer. We analysed the biochemical
      response and toxicity of patients who underwent this therapy at our centre.
      MATERIAL AND METHOD: We selected patients who experienced oligorecurrence between
      January 2015 to December 2016 and were administered SBRT. The association of
      androgen deprivation (AD) was left in each case to the decision of the tumour
      committee. We describe the clinical situation at diagnosis of oligorecurrence,
      the treatment administered and the biochemical response. We considered a
      biochemical response to be a 50% reduction in the absolute prostate-specific
      antigen (PSA) readings. RESULTS: SBRT was administered to 11 patients with bone
      (82%) and/or lymph node oligometastasis (18%). The treatment regimen for bone
      oligometastasis was 27Gy divided into 3 sessions, while the treatment for lymph
      node oligometastasis reached 70Gy. Seven patients had no treatment at the time of
      diagnosis, 2 were in the castration-resistant phase, 1 patient was in the off
      phase of intermittent AD, and 1 patient had adjuvant AD for pN1. Seven patients
      presented a biochemical response with a PSA reduction of 75-100%. The response
      was not assessable in 4 patients due to the continuing adjuvant AD. With a mean
      follow-up of 10.5 months, only 2 patients had progressed. Grade 1
      gastrointestinal toxicity was detected in only 1 patient. CONCLUSION: Our data
      suggest that the use of SBRT in carefully selected patients with metastatic
      oligorecurrence of prostate cancer can achieve biochemical response and
      potentially delay progression and the use of systemic treatments.

PMID- 28739143
TI  - Prediction of time-integrated activity coefficients in PRRT using simulated
      dynamic PET and a pharmacokinetic model.
AB  - PURPOSE: To investigate the accuracy of predicted time-integrated activity
      coefficients (TIACs) in peptide-receptor radionuclide therapy (PRRT) using
      simulated dynamic PET data and a physiologically based pharmacokinetic (PBPK)
      model. METHODS: PBPK parameters were estimated using biokinetic data of 15
      patients after injection of (152+/-15)MBq of 111In-DTPAOC (total peptide amount
      (5.78+/-0.25)nmol). True mathematical phantoms of patients (MPPs) were the PBPK
      model with the estimated parameters. Dynamic PET measurements were simulated as
      being done after bolus injection of 150MBq 68Ga-DOTATATE using the true MPPs.
      Dynamic PET scans around 35min p.i. (P1), 4h p.i. (P2) and the combination of P1
      and P2 (P3) were simulated. Each measurement was simulated with four frames of
      5min each and 2 bed positions. PBPK parameters were fitted to the PET data to
      derive the PET-predicted MPPs. Therapy was simulated assuming an infusion of
      5.1GBq of 90Y-DOTATATE over 30min in both true and PET-predicted MPPs. TIACs of
      simulated therapy were calculated, true MPPs (true TIACs) and predicted MPPs
      (predicted TIACs) followed by the calculation of variabilities v. RESULTS: For P1
      and P2 the population variabilities of kidneys, liver and spleen were acceptable
      (v<10%). For the tumours and the remainders, the values were large (up to 25%).
      For P3, population variabilities for all organs including the remainder further
      improved, except that of the tumour (v>10%). CONCLUSION: Treatment planning of
      PRRT based on dynamic PET data seems possible for the kidneys, liver and spleen
      using a PBPK model and patient specific information.

PMID- 28739144
TI  - Contrast Enhancement in Breast Cancer and Background Mammary-Gland Tissue During
      the Super-Early Phase of Dynamic Breast Magnetic Resonance Imaging.
AB  - RATIONALE AND OBJECTIVES: We aimed to compare the contrast enhancement between
      tumor and mammary-gland tissue to distinguish lesions in the super-early phase,
      during which minimal contrast media uptake is observed in mammary-gland tissue.
      MATERIALS AND METHODS: Dynamic magnetic resonance imaging, including the super
      early phase with bolus tracking (BT) method (to determine the optimal imaging
      start time), was performed by using identical parameters to obtain transverse fat
      suppressed T1-weighted images of both breasts. The percent enhancement (PE) and
      the contrast ratio (CR) indicators for tumor and mammary-gland tissue were
      assessed in each dynamic phase. RESULTS: The PE values of the tumor were 62.4%
      and 151.6%, and those of the mammary gland were 0.3% and 20.7% in the super-early
      and early phases, respectively. Therefore, virtually no background parenchymal
      enhancement was observed in the super-early phase. The variation in the PE values
      during the super-early phase was significantly smaller when the values were
      determined with the BT method (P < .05). The CR was highest in the early phase,
      and the CR in the super-early phase was lower than in the other phases. Early
      phase PE and CR were significantly higher in invasive cancer cases than in
      noninvasive cancer cases (P < .01). A significant difference in the imaging start
      time was observed for the anatomic side factor by the BT method. CONCLUSION:
      Background parenchymal enhancement almost never appeared in the super-early
      phase, but the CR was lower in the super-early phase than in the early phase. The
      BT method allowed for an optimal imaging start time for the super-early phase and
      yielded images with less deviation of contrast enhancement.

PMID- 28739145
TI  - RIFM fragrance ingredient safety assessment, Citronellyl nitrile, CAS Registry
      Number 51566-62-2.

PMID- 28739146
TI  - Relative toxicological ranking of eight polybrominated diphenyl ether congeners
      using cytotoxicity, chemical properties and exposure data.
AB  - Polybrominated diphenyl ethers are widely used flame retardants which persist and
      diffuse in the environment thus entering the food chain. Eight congeners, most
      relevant for human exposure (BDE-28, 47, 99, 100, 153, 154, 183 and 209), were
      analyzed in vitro and in silico to derive a relative toxicological ranking.
      Cytotoxicity was assessed on human liver (HepG2) and colon (DLD-1) cell lines, by
      three assays (MTS, ATP and DNA content) in a range of realistic concentration
      (1pM - 10 nM). Jejunum and Caco-2 passive absorptions were calculated in silico.
      Exposure estimates were calculated using EFSA database. By ToxPi we integrated
      the overall data. No reduction of DNA content was observed, supporting absence of
      cytotoxicity. Otherwise, hormetic effects were exerted by all the congeners,
      except BDE-183. BDE-28, 47, 99, 100 differently affected the ATP content inducing
      a dose-related increase in HepG2 and depletion in DLD-1. Jejunum coefficients did
      not differ among congeners, whereas a higher Caco-2 coefficient indicates rapid
      absorption of BDE-28. ToxPi relative rankings support the toxicological relevance
      of BDE-153 and 28 congeners for their potential hazard; the inclusion of exposure
      data in young and adult populations shifted BDE-209 and BDE-47 as top ranked due
      to their widespread occurrence in the diet.

PMID- 28739147
TI  - Probabilistic exposure assessment of sun care products.
AB  - The aim of this study has been to assess the consumption and the exposure to 6
      types of sun care products: sunscreen cream, sunscreen milk, sunscreen spray,
      sunscreen stick, moisturizing cream with SPF and after-sun milk. Consumption data
      were obtained from 75 clinical safety studies conducted on 3001 subjects: 371
      children aged 3-9, 149 children aged 10-14 and 2481 adults aged more than 15.
      Exposure was assessed using a probabilistic method. Strength of the study include
      stratification of consumption and exposure data according to sex and age, as well
      as other important points such as the galenic form, the site of application and
      the value of the sun protection factor.

PMID- 28739148
TI  - Food insecurity and adult overweight/obesity: Gender and race/ethnic disparities.
AB  - The majority of the food insecurity-obesity research has indicated a positive
      association among women, especially minority women. Less research has been
      conducted on men, and the findings are inconsistent. The aim was to assess
      whether gender and race/ethnic disparities exists between the food insecurity and
      overweight/obesity relationship among adults ages 18-59. We used the cross
      sectional 2011 and 2012 National Health Interview Survey data (N = 19,990). Three
      or more affirmative responses on the 10-item USDA Food Security Scale indicated
      food insecure experiences. Self-reported height and weight were used to calculate
      body mass index according to the Centers for Disease Control and Prevention.
      Multivariate logistic regression models were stratified by gender and
      race/ethnicity to estimate the association between food insecurity and
      overweight/obesity controlling for several demographic characteristics. Adults on
      average were 36 years of age (51% female; 56% white, 27% Hispanic, and 17%
      black), 27% were food insecure, and 65% were overweight/obese. Food insecurity
      was most prevalent among blacks and Hispanics, regardless of gender. A greater
      percentage of food insecure women were overweight/obese compared to food secure
      women among all race/ethnicity groups; while similar proportions of white, black,
      and Hispanic men were overweight/obese irrespective of their food security
      status. In covariate-adjusted models, food insecurity was associated with a 41%
      and 29% higher odds of being overweight/obese among white and Hispanic women,
      respectively. Food insecurity was not related to overweight/obesity among black
      women nor among white, black, and Hispanic men. The complex relationship between
      food insecurity and obesity suggests a need to investigate potential behavioral
      and physiological mechanisms, and moderators of this relationship.

PMID- 28739149
TI  - Oral Medication for Agitation of Psychiatric Origin: A Scoping Review of
      Randomized Controlled Trials.
AB  - BACKGROUND: Understanding more about the efficacy and safety of oral second
      generation antipsychotic medications in reducing the symptoms of acute agitation
      could improve the treatment of psychiatric emergencies. OBJECTIVE: The objective
      of this scoping review was to examine the evidence base underlying expert
      consensus panel recommendations for the use of oral second-generation
      antipsychotics to treat acute agitation in mentally ill patients. METHODS: The
      Cochrane Schizophrenia Group's Study-Based Register was searched for randomized
      controlled trials comparing oral second-generation antipsychotics,
      benzodiazepines, or first-generation antipsychotics with or without adjunctive
      benzodiazepines, irrespective of route of administration of the drug being
      compared. Six articles were included in the final review. RESULTS: Two oral
      second-generation antipsychotic medications were studied across the six included
      trials. While the studies had relatively small sample sizes, oral second
      generation antipsychotics were similarly effective to intramuscular first
      generation antipsychotics in treating symptoms of acute agitation and had similar
      side-effect profiles. CONCLUSIONS: This scoping review identified six randomized
      trials investigating the use of oral second-generation antipsychotic medications
      in the reduction of acute agitation among patients experiencing psychiatric
      emergencies. Further research will be necessary to make clinical recommendations
      due to the overall dearth of randomized trials, as well as the small sample sizes
      of the included studies.

PMID- 28739150
TI  - Plasma assisted surface treatments of biomaterials.
AB  - The biocompatibility of an implant depends upon the material it is composed of,
      in addition to the prosthetic device's morphology, mechanical and surface
      properties. Properties as porosity and pore size should allow, when required,
      cells penetration and proliferation. Stiffness and strength, that depend on the
      bulk characteristics of the material, should match the mechanical requirements of
      the prosthetic applications. Surface properties should allow integration in the
      surrounding tissues by activating proper communication pathways with the
      surrounding cells. Bulk and surface properties are not interconnected, and for
      instance a bone prosthesis could possess the necessary stiffness and strength for
      the application omitting out prerequisite surface properties essential for the
      osteointegration. In this case, surface treatment is mandatory and can be
      accomplished using various techniques such as applying coatings to the
      prosthesis, ion beams, chemical grafting or modification, low temperature plasma,
      or a combination of the aforementioned. Low temperature plasma-based techniques
      have gained increasing consensus for the surface modification of biomaterials for
      being effective and competitive compared to other ways to introduce surface
      functionalities. In this paper we review plasma processing techniques and
      describe potentialities and applications of plasma to tailor the interface of
      biomaterials.

PMID- 28739151
TI  - The Effect of Immediate Breast Reconstruction on Thoracic Spine Alignment After
      Unilateral Mastectomy.
AB  - BACKGROUND: Long-term posture change after unilateral mastectomy in breast cancer
      patients can affect spinal alignment during the postoperative period. We
      evaluated the effect of immediate breast reconstruction on body posture after
      surgery by analyzing spinal alignment with radiographic studies. MATERIALS AND
      METHODS: Preoperative and 2-year postoperative chest radiographs of 116 patients
      who received immediate breast reconstruction with unilateral mastectomy and 250
      patients who underwent unilateral mastectomy without reconstruction were
      retrospectively reviewed. Cobb angle, the direction of spinal curvature, upper
      and lower ends of the thoracic curve, and curve length were measured and compared
      between both groups. Additional patient information including age, height,
      weight, body mass index, and side of surgery were collected via chart review.
      RESULTS: There was a significant difference in the Cobb angle between the
      preoperative and 2-year postoperative chest radiographs between the immediate
      breast reconstruction group and mastectomy group. Without considering curvature
      change, the difference was -0.593 degrees  in the reconstruction group and 2.698
      degrees  in the mastectomy-alone group (P = .02), and considering curvature
      change, the difference was 0.335 degrees  and 3.972 degrees  in the
      reconstruction and mastectomy-alone group, respectively (P < .01). CONCLUSION:
      The amount of change in postoperative spinal alignment was significantly smaller
      in the immediate breast reconstruction group compared with patients who received
      only unilateral mastectomy without reconstruction. We suggest that immediate
      breast reconstruction positively affects spinal alignment, leading to better
      posture and physical function.

PMID- 28739152
TI  - NSL_ 32671: Retraction notice to Early hyperbaric oxygen therapy may improve the
      long term neurological consequences of diabetic patients suffering from
      hemorrhagic stroke [Neuroscience Letters 644 (2017) 83-86].

PMID- 28739153
TI  - Active Donor Management During the Hospital Phase of Care Is Associated with More
      Organs Transplanted per Donor.
AB  - BACKGROUND: Meeting donor management goals when caring for potential organ donors
      has been associated with more organs transplanted per donor (OTPD). Concern
      persists, however, as to whether this indicates that younger/healthier donors are
      more likely to meet donor management goals or whether active management affects
      outcomes. STUDY DESIGN: A prospective observational study of all standard
      criteria donors was conducted by 10 organ procurement organizations across United
      Network for Organ Sharing Regions 4, 5, and 6. Donor management goals
      representing normal critical care end points were measured at 2 time points: when
      a catastrophic brain injury was recognized and a referral was made to the organ
      procurement organization by the DH; and after brain death was declared and
      authorization for organ donation was obtained. Donor management goals Bundle
      "met" was defined as achieving any 7 of 9 end points. A positive Bundle status
      change was defined as not meeting the Bundle at referral and subsequently
      achieving it at authorization. The primary outcomes measure was having >=4 OTPD.
      RESULTS: Data were collected for 1,398 standard criteria donors. Of the 1,166
      (83%) who did not meet the Bundle at referral, only 254 (22%) had a positive
      Bundle status change. On adjusted analysis, positive Bundle status change
      increased the odds of achieving >=4 OTPD significantly (odds ratio 2.04; 95% CI
      1.49 to 2.81; p < 0.001). CONCLUSIONS: A positive donor management goal Bundle
      status change during donor hospital management is associated with a 2-fold
      increase in achieving >=4 OTPD. Active critical care management of the potential
      organ donor, as evidenced by improvement in routinely measured critical care end
      points can be a means by which to substantially increase the number of organs
      available for transplantation.

PMID- 28739154
TI  - Prostaglandin E2: A Pancreatic Fluid Biomarker of Intraductal Papillary Mucinous
      Neoplasm Dysplasia.
AB  - BACKGROUND: With the increased frequency of diagnostic imaging, pancreatic cysts
      are now detected in >3% of American adults. Most of these are intraductal
      papillary mucinous neoplasms (IPMNs) with well-established but variable malignant
      potential. A biomarker that predicts malignant potential or dysplastic grade
      would help determine which IPMNs require removal and which can be observed
      safely. We previously reported that pancreatic fluid prostaglandin E2 (PGE2)
      levels might have promise as a predictor of IPMN dysplasia and we seek to
      validate those results in the current study. STUDY DESIGN: Pancreatic cyst/duct
      fluid was prospectively collected from 100 patients with IPMN undergoing
      pancreatic resection. Surgical pathology revealed 47 low-/moderate-grade, 34 high
      grade, and 20 invasive IPMNs. The PGE2 levels were assessed by ELISA and
      correlated with IPMN dysplasia grade, demographics, clinical
      radiologic/pathologic variables, acute/chronic pancreatitis, and NSAID use.
      RESULTS: Mean pancreatic cyst fluid PGE2 levels in high-grade and invasive IPMNs
      were significantly higher than low-/moderate-grade IPMNs (3.5 and 4.4 pg/MUL,
      respectively, vs 1.2 pg/MUL; p < 0.0016). At a threshold of 1.1 pg/MUL, PGE2 was
      63% sensitive, 79% specific, and 71% accurate for detection of high
      grade/invasive IPMNs. When tested in the subset of IPMN patients with
      preoperative pancreatic cyst fluid CEA >192 ng/mL, PGE2 at a threshold of 0.5
      pg/MUL demonstrated 78% sensitivity, 100% specificity, and 86% accuracy for
      detection of high-grade/invasive IPMN. CONCLUSIONS: Our results validate
      pancreatic cyst fluid PGE2 as an indicator of IPMN dysplasia, especially in
      select patients with preoperative pancreatic cyst fluid CEA >192 ng/mL. The
      inclusion of PGE2/CEA in a diagnostic biomarker panel can facilitate more optimal
      treatment stratification of IPMN patients.

PMID- 28739155
TI  - Discovery of a low-systemic-exposure DGAT-1 inhibitor with a
      picolinoylpyrrolidine-2-carboxylic acid moiety.
AB  - A series of diacylglycerol O-acyltransferase 1 (DGAT-1) inhibitors with a
      picolinoylpyrrolidine-2-carboxylic acid moiety were designed and synthesized. Of
      these compounds, compound 22 exhibited excellent DGAT-1-inhibitory activity
      (hDGAT-1 enzyme assay, 50% inhibitory concentration [IC50]=3.5+/-0.9nM) and
      effectively reduced the intracellular triglyceride contents in 3T3-L1, HepG2 and
      Caco-2 cells. A preliminary study of the plasma and tissue distributions of
      compound 22 in mice revealed low plasma exposure and high concentrations in
      different segments of the intestine and liver, which may facilitate targeting
      DGAT-1. Furthermore, in an acute lipid challenge test, compound 22 showed a dose
      dependent inhibitory effect on high-serum triglycerides in C57/KSJ mice induced
      by olive oil (1, 3, and 10mg/kg, i.g.).

PMID- 28739156
TI  - Synthesis and biological evaluation in vitro and in mammalian cells of new
      heteroaryl carboxyamides as HIV-protease inhibitors.
AB  - New heteroaryl HIV-protease inhibitors bearing a carboxyamide spacer were
      synthesized in few steps and high yield, from commercially available homochiral
      epoxides. Different substitution patterns were introduced onto a given
      isopropanoyl-sulfonamide core modifying the type of heteroarene and the central
      core, with the presence of either H or benzyl group. Their in vitro inhibition
      activity against recombinant protease showed a general beneficial effect of
      carboxyamide moiety, the IC50 values ranging between 1 and 15nM. In particular
      benzofuryl derivatives showed IC50 values among the best for such structurally
      simple inhibitors. Docking analysis allowed to identify the favorable situation
      of such benzofuryl derivatives in terms of number of interactions in the active
      site, supporting the experimental results on activity. The inhibition activity of
      such molecules has been also evaluated in HEK293 cells expressing the protease
      fused to green fluorescent protein, by western blotting analysis, fluorescence
      microscopy and cytofluorimetry.

PMID- 28739157
TI  - Cycloalkane analogues of sinefungin as EHMT1/2 inhibitors.
AB  - A series of cycloalkyl substituted analogues of the natural product sinefungin
      lacking the amino-acid moiety was designed and synthesized. Two stereoisomers (6
      R and 6-S) were separated and their bioactivities examined against EHMT1/2. Of
      which, compound 14d showed an inhibitory activity against EHMT1/2 (88.9%,
      IC50=21.8MUM for EHMT1 and 77.6%, IC50=39.6MUM for EHMT2, respectively) similar
      to that of sinefungin (100.0%, IC50=28.4MUM for EHMT1 and 79.5%, IC50=30.1MUM for
      EHMT2, respectively). Further studies against other methyltransferases such as
      PRMT1 showed no activity except that 12d displayed about 20% inhibition.

PMID- 28739158
TI  - Assessment and management of radiotherapy induced toxicity in older patients.
AB  - Radiotherapy is an attractive treatment option for older adults, especially where
      surgery and chemotherapy pose too great a risk. Radiotherapy toxicity may be
      divided into acute/early and late effects of treatment. The latter may have
      limited relevance to an older patient with competing causes of mortality due to
      significant comorbidity. Altered fractionation regimes have been employed in
      numerous sites, with no significant toxicity impact. These offer greater
      convenience in the elderly, especially those with limited social support or in
      active caregiving roles. As radiotherapy toxicity is site specific, it's
      important to assess baseline function via Comprehensive Geriatric Assessment
      (CGA), and any pre-existing comorbidities that may influence toxicity. With
      modern radiotherapy technology and capabilities, these are less of an issue and
      radiotherapy is a very suitable treatment option for the older adult. When
      evaluating the literature on toxicity in older patients, it's important to
      recognise that older studies do not represent modern day radiotherapy techniques
      and capabilities. Advanced technology may simultaneously deliver enhanced target
      coverage and reduced toxicity. More research is required related to the
      predictive power of CGA in linking radiotherapy toxicity to frailty. What little
      evidence exists shows that CGA has a role in treatment of older patients with
      radiotherapy and that, in general, radiotherapy appears to be well tolerated in
      older adults. The purpose of this review is to provide a broad overview of the
      mechanisms of normal tissue reactions to radiotherapy and how radiation induced
      toxicity may affect older patients.

PMID- 28739159
TI  - Lung stereotactic body radiation therapy (SBRT) for early-stage non-small cell
      lung cancer in the very elderly (>=80years old): Extremely safe and effective.
AB  - OBJECTIVE: Stereotactic body radiotherapy (SBRT) for early-stage non-small-cell
      lung cancer (NSCLC) is the standard of care in medically inoperable patients. In
      very elderly patients, previous studies have shown SBRT to offer excellent local
      control, though with higher toxicities than in younger populations. We report our
      institutional experience using SBRT in the definitive management of NSCLC in
      patients >=80years old. MATERIALS AND METHODS: Using an IRB-approved registry of
      158 patients treated with definitive-intent lung SBRT for early-stage NSCLC at
      our institution between 2010 and 2016, 31 consecutively treated patients
      >=80years of age were identified. CTCAEv4 scales were prospectively recorded
      during follow-ups and utilized for toxicity assessments. Kaplan-Meier estimates
      were utilized for survival analyses. RESULTS: For the 31 patients (with 34
      lesions) included, median age was 83 (R: 80-93), median ECOG performance status
      was 2 (R: 0-3), and median follow-up was 15.8months (R: 3.1-48.3). Median PTV
      size was 24.0cm3 (R: 5.83-62.1cm3). Median prescription dose was 54Gy in 3
      fractions (R: 50-60Gy in 3-8 fractions). Local control was 100% at 1year and
      92.3% at 2years. Median survival was 29.1months. There were no grade 2-5
      toxicities. Grade 1 toxicities included: fatigue in 5 patients (16.1%),
      asymptomatic (radiographic) pneumonitis in 12 (38.7%), and dyspnea in 2 (6.5%).
      CONCLUSIONS: Lung SBRT with a BED of >=100Gy10 for very elderly patients with
      NSCLC is extremely safe and effective, with inordinately low toxicity rates (zero
      grade 2-5 toxicities). With stringent dosimetric parameters and planning
      guidelines, patients >=80years remain excellent candidates for full-dose SBRT.
      SUMMARY: SBRT for early-stage NSCLC is the accepted standard of care in medically
      inoperable patients, though in many very elderly patients, dose is either de
      intensified or withheld for concern of toxicity in the setting of advanced age
      and competing risks. In this study of our very elderly (>=80years old) early
      stage NSCLC patients, we highlight both the extremely high efficacy and
      tolerability (zero grade 2 or above toxicities) associated with definitive intent
      SBRT.

PMID- 28739160
TI  - Using heat maps to assess the multidimensional association of comorbidities with
      survival in older cancer patients treated with chemotherapy.
AB  - OBJECTIVE: To date, most comorbidity studies have analyzed either a subgroup of
      frequent diseases, or used summary instruments such as the Charlson score or the
      Cumulative Illness Rating Scale-Geriatric (CIRS-G). Yet, comorbidity is a
      multidimensional construct and impacts function, treatment tolerance, and
      survival. We assessed how heat maps can unveil specific patterns of comorbidities
      associated with overall survival (OS) in older cancer patients treated with
      chemotherapy. MATERIAL AND METHODS: We reviewed four trials that prospectively
      evaluated comorbidities using CIRS-G. Eligible patients were 65years or older and
      had solid tumors with 30 or more patients per tumor site. Heat maps were
      constructed based on CIRS-G scores and correlated with OS. RESULTS: Among 818
      patients accrued, 399 were eligible: Median follow-up was 53.4months and median
      OS was 19.6months (95% CI: 16.5-24.2). In the univariate model for OS, patients
      with a severe CIRS-G score in 6 organ categories (3-4 in heart, hematopoietic,
      respiratory, and musculoskeletal-integument and 2-4 in upper GI and liver) had
      statistically worse OS than those with lower scores. According to a total risk
      score (TRS) based on hazard ratios for OS, OS of the low risk group (N=309,
      TRS<2) was significantly higher (24.3m vs. 10.8m, HR=2.05, 95% CI: 1.58-2.66).
      TRS was a predictor for OS independently from stage, primary site, prior
      chemotherapy, ECOG performance status, and IADL (HR=1.94, 95% CI: 1.47-2.57).
      CONCLUSIONS: High TRS was a predictor of poor survival. Comorbidity heat maps
      appear promising to identify diseases most affecting the OS of older cancer
      patients.

PMID- 28739161
TI  - Automated face recognition of rhesus macaques.
AB  - BACKGROUND: Rhesus macaques are widely used in biomedical research. Automated
      behavior monitoring can be useful in various fields (including neuroscience), as
      well as having applications to animal welfare but current technology lags behind
      that developed for other species. One difficulty facing developers is the
      reliable identification of individual macaques within a group especially as pair-
      and group-housing of macaques becomes standard. Current published methods require
      either implantation or wearing of a tracking device. NEW METHOD: I present face
      recognition, in combination with face detection, as a method to non-invasively
      identify individual rhesus macaques in videos. The face recognition method
      utilizes local-binary patterns in combination with a local discriminant
      classification algorithm. RESULTS: A classification accuracy of between 90 and
      96% was achieved for four different groups. Group size, number of training images
      and challenging image conditions such as high contrast all had an impact on
      classification accuracy. I demonstrate that these methods can be applied in real
      time using standard affordable hardware and a potential application to studies of
      social structure. COMPARISON WITH EXISTING METHOD(S): Face recognition methods
      have been reported for humans and other primate species such as chimpanzees but
      not rhesus macaques. The classification accuracy with this method is comparable
      to that for chimpanzees. Face recognition has the advantage over other methods
      for identifying rhesus macaques such as tags and collars of being non-invasive.
      CONCLUSIONS: This is the first reported method for face recognition of rhesus
      macaques, has high classification accuracy and can be implemented in real time.

PMID- 28739162
TI  - Refining forelimb asymmetry analysis: Correlation with Montoya staircase
      contralateral function post-stroke.
AB  - BACKGROUND: Forelimb Asymmetry Test is a simple test of motor function, using
      exploration behavior of a rat in a novel environment and counting the number of
      times that a rat touches the wall with either forepaw. Our lab has noticed,
      however, that there appears to be an increased number of fingertip touches to the
      wall following a stroke in the impaired forelimb. NEW METHOD: We counted the
      number of times that the animal either laid its palm flat against the wall of the
      chamber or touched the wall with only its fingertips, for both the left and right
      forepaws. We also separated bouts of exploration, so we could clearly determine
      if fingertip touches normally were associated with a transition from resting
      state to exploration state. RESULTS AND COMPARISON WITH EXISTING METHODS: Fishers
      exact test indicated that there were significant differences in the way that the
      animals touched the wall pre-stroke compared to post-stroke, with more fingertip
      touches occurring post-stroke. Counting palm touches as normal and fingertip
      touches as abnormal increases the sensitivity of the Forelimb Asymmetry analysis
      and gives a good correlation with the contralateral functional deficits
      determined by Montoya Staircase post-stroke. If we counted every wall touch as
      normal (palm touches and fingertip touches), we see a loss of sensitivity and a
      poor correlation with contralateral function as determined by Montoya Staircase.
      CONCLUSIONS: This refinement of the Forelimb Asymmetry analysis improves
      correlation with Montoya Staircase contralateral function after stroke.

PMID- 28739163
TI  - Strategies for statistical thresholding of source localization maps in
      magnetoencephalography and estimating source extent.
AB  - BACKGROUND: Magnetoencephalography allows defining non-invasively the spatio
      temporal activation of brain networks thanks to source localization algorithms. A
      major difficulty of MNE and beamforming methods, two classically used techniques,
      is the definition of proper thresholds that allow deciding the extent of
      activated cortex. NEW METHOD: We investigated two strategies for computing a
      threshold, taking into account the difficult multiple comparison issue. The
      strategies were based either on parametric statistics (Bonferroni, FDR
      correction) or on empirical estimates (local FDR and a custom measure based on
      the survival function). RESULTS: We found thanks to the simulations that
      parametric methods based on the sole estimation of H0 (Bonferroni, FDR) performed
      poorly, in particular in high SNR situations. This is due to the spatial leakage
      originating from the source localization methods, which give a 'blurred'
      reconstruction of the patch extension: the higher the SNR, the more this effect
      is visible. COMPARISON WITH EXISTING METHODS: Adaptive methods such as local FDR
      or our proposed 'concavity threshold' performed better than Bonferroni or
      classical FDR. We present an application to real data originating from auditory
      stimulation in MEG. CONCLUSION: In order to estimate source extent, adaptive
      strategies should be preferred to parametric statistics when dealing with
      'leaking' source reconstruction algorithms.

PMID- 28739164
TI  - A sparse representation-based method for parcellation of the resting brain and
      its application to treatment-resistant major depressive disorder.
AB  - BACKGROUND: Parcellating brain regions into functionally homogeneous subdivisions
      is critical for understanding normal and abnormal brain functions. NEW METHOD: In
      this study, we developed a new sparse representation-based parcellation method
      for functional magnetic resonance imaging (fMRI) data, and applied the new method
      to investigate functional insular subdivisions in treatment-resistant major
      depressive disorder (MDD). Realistic simulations were implemented to demonstrate
      the feasibility of the method. Subsequently, the method was used to parcellate
      the insula in a sample of fifty-six MDD patients and thirty-six healthy
      volunteers (HVs). The optimal number of clusters was determined by an independent
      test-retest dataset. Finally, differences of the functional connectivity profiles
      of each insular subdivision between patients and HVs were inspected. RESULTS: The
      results from both simulated and test-retest fMRI datasets demonstrated the
      feasibility of the proposed elastic net-based (EN) method. With the proposed
      method, the insula was parcellated into four subdivisions (dorsal anterior dAI;
      ventral anterior vAI; middle, MI and posterior, PI). Whereas patients showed hypo
      connectivity between vAI and right medial temporal lobe, there were no functional
      volumetric differences in insular subdivisions between MDD patients and HVs.
      COMPARISON WITH EXISTING METHOD: Results from both simulated and real fMRI
      datasets showed that the proposed EN method achieved higher accuracy than least
      absolute shrinkage and selection operator-based (LASSO) method. CONCLUSIONS:
      These findings suggest that EN-based parcellation has the potential to be a
      useful addition to the parcellation techniques for fMRI data, and provide
      evidence of decreased functional connectivity without functional volumetric
      changes of the insula in treatment-resistant MDD.

PMID- 28739165
TI  - Quantitative models of feline lumbosacral dorsal root ganglia neuronal cell
      density.
AB  - BACKGROUND: Dorsal root ganglia (DRG) are spinal root components that contain the
      cell bodies of converging primary sensory neurons. DRG are becoming a therapeutic
      target for electrical neural interfaces. Our purpose was to establish methods for
      quantifying the non-random nature and distribution of neuronal cell bodies within
      DRG. NEW METHOD: We identified neuronal cell body locations in 26 feline
      lumbosacral DRG cross-section histological images and used computational tools to
      quantify spatial trends. We first analyzed spatial randomness using the nearest
      neighbor distance method. Next we overlaid a 6*6 grid, modeling neuronal cellular
      density in each grid square and comparing regions statistically. Finally we
      transformed DRG onto a polar map and calculated neuronal cellular density in
      annular sectors. We used a recursive partition model to determine regions of high
      and low density, and validated the model statistically. RESULTS: We found that
      the arrangement of neuronal cell bodies at the widest point of DRG is distinctly
      non-random with concentration in particular regions. The grid model suggested a
      radial trend in density, with increasing density toward the outside of the DRG.
      The polar transformation model showed that the highest neuronal cellular density
      is in the outer 23.9% radially and the dorsal +/-61.4 degrees  angularly.
      COMPARISON WITH EXISTING METHODS: To our knowledge, DRG neuronal cell
      distribution has not been previously quantified. CONCLUSIONS: These results
      confirm and expand quantitatively on the existing understanding of DRG anatomy.
      Our methods can be useful for analyzing the distribution of cellular components
      of other neural structures or expanding to three-dimensional models.

PMID- 28739166
TI  - Characterizing activation mechanisms and binding preferences of ruthenium metallo
      prodrugs by a competitive binding assay.
AB  - The activation mechanisms and reactivity of ruthenium metallo-prodrug lead
      structures were investigated in detail using capillary zone electrophoresis mass
      spectrometry (CZE-MS) in a time-dependent manner and by exposing to a
      protein/oligonucleotide mixture. The competitive assays were performed with
      sodium trans-[RuCl4(HInd)2] where Hind=indazole (NKP-1339), [(eta6-p
      cymene)RuCl2(pta)], where pta=1,3,5-triaza-7-phosphaadamantane (RAPTA-C) and
      [(eta6-biphenyl)RuCl(1,2-ethylenediamine)]PF6 (RM175). Molecular and quantitative
      information on binding preferences was obtained by coupling CZE to electrospray
      ionization MS (ESI-MS) and inductively coupled plasma MS (ICP-MS), respectively.
      A score system is presented that ranks the binding preferences of Ru complexes
      with nucleotides and demonstrated the following trend of decreasing selectivity
      after 24h: RM175 (0.89)>RAPTA-C (0.78)>NKP-1339 (0.40). As expected, the
      organometallic drug candidates RM175 and RAPTA-C underwent a halido/aqua ligand
      exchange reaction at the metal center and showed distinct reactivity towards the
      biomolecules. In particular, the protein/DNA binding sites of RAPTA-C in a
      mixture of protein (ubiquitin) and oligonucleotide (5'-dATTGGCAC-3') were located
      at single-amino acid and single-nucleotide resolution, respectively. Activated
      RAPTA-C bound selectively to Met1, adenine and cytosine in this setting, which
      contrasts with the selectivity of RM175 for guanine. Finally, activation products
      of NKP-1339 were detected corresponding to RuII(Hind)2 fragments coordinated to
      the oligonucleotide, which represents one of the few examples of a directly
      observed RuII adduct.

PMID- 28739167
TI  - Establishment of NF-kappaB sensing and interleukin-4 secreting mesenchymal
      stromal cells as an "on-demand" drug delivery system to modulate inflammation.
AB  - Chronic inflammation is associated with up-regulation of the transcription factor
      nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and
      excessive inflammatory cytokine secretion by M1 macrophages. The anti
      inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages
      into an anti-inflammatory and tissue-regenerative M2 phenotype, thus reducing
      inflammation and enhancing tissue regeneration. We have generated NF-kappaB
      responsive, or constitutively active IL-4 expression lentiviral vectors
      transduced into murine bone marrow-derived mesenchymal stromal cells (MSCs). MSCs
      with a constitutively active IL-4 expression vector produced large quantities of
      IL-4 continuously, whereas IL-4 secretion was significantly induced by
      lipopolysaccharide (LPS) in the NF-kappaB sensing MSCs. In contrast, LPS had no
      effect on MSCs with IL-4 secretion driven by a constitutively active promoter. We
      also found that intermittent and continuous LPS treatment displayed distinct NF
      kappaB activation profiles, and this regulation was independent of IL-4
      signaling. The supernatant containing IL-4 from the LPS-treated MSCs suppressed
      M1 marker (inducible nitric oxide synthase [iNOS] and tumor necrosis factor alpha
      [TNFalpha]) expression and enhanced M2 marker (Arginase 1, CD206 and IL1 receptor
      antagonist [IL1Ra]) expression in primary murine macrophages. The IL-4 secretion
      at the basal, non-LPS induced level was sufficient to suppress TNFalpha and
      enhance Arginase 1 at a lower level, but had no significant effects on iNOS,
      CD206 and IL1Ra expression. Finally, IL-4 secretion at basal or LPS-induced
      levels significantly suppressed osteogenic differentiation of MSCs. Our findings
      suggest that the IL-4 secreting MSCs driven by NF-kappaB sensing or constitutive
      active promoter have great potential for mitigating the effects of chronic
      inflammation and promoting earlier tissue regeneration.

PMID- 28739168
TI  - Adipose-derived stem cell spheroid treated with low-level light irradiation
      accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia.
AB  - BACKGROUND AIMS: We investigated whether low-level light irradiation (LLLI)
      before adipose-derived stromal cells (ASCs) spheroid transplantation improved
      hind-limb functional recovery by stimulation of angiogenesis. METHODS: The
      spheroid, composed of ASCs, was irradiated with low-level light and expressed
      angiogenic factors, including vascular endothelial growth factor and basic
      fibroblast growth factor. From immunochemical staining analysis, the spheroid of
      ASCs included CD31+, KDR+ and CD34+, whereas monolayer-cultured ASCs were
      negative for these markers. To evaluate the therapeutic effect of the ASC
      spheroid treated with LLLI in vivo, phosphate-buffered saline, monolayer ASCs,
      LLLI-monolayer ASCs, spheroid ASCs and LLLI-spheroid ASCs were transplanted into
      a hind-limb ischemia model. RESULTS: The LLLI-spheroid ASCs transplanted into the
      hind-limb ischemia differentiated into endothelial cells and remained
      differentiated. Transplantation of LLLI-spheroid ASCs into the hind-limb ischemia
      significantly elevated the density of vascular formations through angiogenic
      factors released by the ASCs and enhanced tissue regeneration at the lesion site.
      Consistent with these results, the transplantation of LLLI-spheroid ASCs
      significantly improved functional recovery compared with ASC or spheroid ASC
      transplantation and PBS treatment. CONCLUSIONS: These findings suggest that
      transplantation of ASC spheroid treated with LLLI may be an effective stem cell
      therapy for the treatment of hind-limb ischemia and peripheral vascular disease.

PMID- 28739169
TI  - Development and application of a perioral force measurement system for infants
      with cleft lip and palate.
AB  - BACKGROUND: Muscles converge or intertweave around the perioral area, and this
      can be treated with sequential therapy in infants with cleft lip and palate
      (CLP). The force of perioral muscles has a great influence on maxillary
      development and morphology. Perioral force in infants with CLP has not been well
      studied, and accurate and reliable measurement of perioral force in infants
      remains a challenge. This study aimed to investigate a new way to accurately and
      reliably measure perioral force in infants with unilateral CLP (UCLP) and explore
      the change before and after cheiloplasty. STUDY DESIGN: A perioral force
      measurement system was developed and applied to measure perioral force at labial
      frenum area and the commissures on both the normal and the cleft sides of four
      infants with UCLP before and after cheiloplasty. The results were analyzed using
      the SPSS 19.0 software. RESULTS: The perioral force measurement system appears to
      produce valid results in infants with UCLP. Before cheiloplasty, the perioral
      force of labial frenum area was 1.79 +/- 0.94 g/cm2 and that of commissure on the
      normal and cleft sides was 5.41 +/- 1.01 g/cm2 and 3.12 +/- 1.55 g/cm2,
      respectively (P < 0.05). After cheiloplasty, perioral force of labial frenum area
      was 12.73 +/- 3.51 g/cm2 and that of commissure on the normal and cleft sides was
      7.64 +/- 1.64 g/cm2 and 7.27 +/- 1.89 g/cm2, respectively (P > 0.05).

PMID- 28739170
TI  - Bilateral buccinator myomucosal flap outcomes in nonsyndromic patients with
      repaired cleft palate and velopharyngeal insufficiency.
AB  - BACKGROUND: The purpose of this study was to assess speech outcomes and
      complication rate in nonsyndromic repaired cleft palate patients undergoing
      bilateral buccinator myomucosal flaps for velopharyngeal insufficiency
      management. METHODS: A prospective study of consecutive repaired cleft palate
      patients with velopharyngeal insufficiency who underwent bilateral buccinator
      myomucosal flaps was conducted. Three experienced evaluators performed a blinded
      perceptual speech evaluation (hypernasality, audible nasal emission, and
      intraoral pressure). Successful speech outcome was defined as normal or
      borderline sufficient velopharyngeal function at 15 months postoperatively.
      Obstructive sleep apnea screening tools were applied preoperatively and
      postoperatively. Complication rate was also collected. RESULTS: Fifty-three
      patients were included. There were 11 (21%) surgical complications, with no
      complete flap loss, snoring, sleep disturbance, and/or mouth breathing. All
      patients presented low pre- and postoperative risk for obstructive sleep apnea.
      At 15 months postoperatively, hypernasality (0.4 +/- 0.6), audible nasal
      emissions (0.2 +/- 0.4), and intraoral pressure (0.1 +/- 0.3) were significantly
      (all p < 0.05) lower than preoperative measurements (hypernasality: 2.7 +/- 0.5;
      audible nasal emissions: 2.2 +/- 0.8; and intraoral pressure: 0.9 +/- 0.3). Forty
      five (85%) patients presented successful speech outcome. CONCLUSION: The
      bilateral buccinator myomucosal flap is an effective and safe surgical strategy
      for the management of persistent velopharyngeal insufficiency.

PMID- 28739171
TI  - Efficacy of ultrasound, mammography and magnetic resonance imaging in detecting
      breast implant rupture: A retrospective study of 175 reconstructive and aesthetic
      sub-pectoral breast augmentation cases.
AB  - To date, the effectiveness of radiological imaging in detecting silicone breast
      implant rupture is uncertain. The purpose of this study is to retrospectively
      evaluate the effectiveness of radiological imaging when diagnosing a rupture. In
      this study, 175 patients with 242 breast implants were included, of which 168 and
      74 implants were used for breast reconstruction and aesthetic augmentation,
      respectively. All patients who underwent revision surgery, between January 2015
      and June 2016, following breast augmentation or reconstruction were included,
      regardless of any pre-operative diagnosis of rupture that had been made. The
      diagnosis of intracapsular rupture was verified intraoperatively and compared to
      the pre-operative findings. With regard to pre-operative diagnostic imaging
      methods, we compared magnetic resonance imaging (MRI), mammography, and
      ultrasonography (US) findings. Among the 242 implants that were explanted, 35
      clinical ruptures were confirmed and compared with the related radiological
      findings. We reported 22 false positives and 15 false negatives. US was the least
      specific and least accurate method because of its lowest positive predictive
      value (PPV) and negative predictive value (NPV). Mammography was the most
      specific and most accurate method, with the highest PPV (96%). Surprisingly, MRI
      was the most sensitive; however, it was neither the most specific nor the most
      accurate method despite having the highest NPV (98%). After comparing these three
      radiological techniques, we conclude that US along with MRI can be useful for
      young patients. Mammography, which was characterised by high specificity and
      accuracy, could be useful along with MRI in investigating patients over the age
      of 40.

PMID- 28739172
TI  - Emergence and maintenance of menopause in humans: A game theory model.
AB  - Menopause, the permanent cessation of ovulation, occurs in women well before the
      end of their expected life span. Several adaptive hypotheses have been proposed
      to solve this evolutionary puzzle, each based on a possible fitness benefit
      derived from an early reproductive senescence, but no consensus has emerged. The
      construction of a game theory model allowed us to jointly study the main adaptive
      hypotheses in emergence and maintenance of menopause. Four classical hypotheses
      on the benefits of menopause were considered (decreased maternal mortality,
      increased grandmothering, decreased conflict over reproductive resources between
      older and younger females, and changes in their relatedness) plus a fifth one
      derived from a possible pleiotropic trade-off. Interestingly, the conditions for
      the emergence of menopause are more restrictive than those for its maintenance
      due to the social and familial changes induced by the occurrence of non
      reproductive older women.

PMID- 28739173
TI  - Lipid droplet proteins and metabolic diseases.
AB  - Lipid droplets (LDs) are ubiquitous cellular organelles for lipid storage which
      are composed of a neutral lipid core bounded by a protein decorated phospholipid
      monolayer. Although lipid storage is their most obvious function, LDs are far
      from inert as they participate in maintaining lipid homeostasis through lipid
      synthesis, metabolism, and transportation. Furthermore, they are involved in cell
      signaling and other molecular events closely associated with human disease such
      as dyslipidemia, obesity, lipodystrophy, diabetes, fatty liver, atherosclerosis,
      and others. The last decade has seen a great increase in the attention paid to LD
      biology. Regardless, many fundamental features of LD biology remain obscure. In
      this review, we will discuss key aspects of LD biology including their
      biogenesis, growth and regression. We will also summarize the current knowledge
      about the role LDs play in human disease, especially from the perspective of the
      dynamics of the associated proteins. This article is part of a Special issue
      entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited
      by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.

PMID- 28739174
TI  - Inhibition of mitochondrial fission prevents hypoxia-induced metabolic shift and
      cellular proliferation of pulmonary arterial smooth muscle cells.
AB  - Chronic hypoxia exacerbates proliferation of pulmonary arterial smooth muscle
      cells (PASMC), thereby reducing the lumen of pulmonary arteries. This leads to
      poor blood oxygenation and cardiac work overload, which are the basis of diseases
      such as pulmonary artery hypertension (PAH). Recent studies revealed an emerging
      role of mitochondria in PAH pathogenesis, as key regulators of cell survival and
      metabolism. In this work, we assessed whether hypoxia-induced mitochondrial
      fragmentation contributes to the alterations of both PASMC death and
      proliferation. In previous work in cardiac myocytes, we showed that trimetazidine
      (TMZ), a partial inhibitor of lipid oxidation, stimulates mitochondrial fusion
      and preserves mitochondrial function. Thus, here we evaluated whether TMZ-induced
      mitochondrial fusion can prevent human PASMC proliferation in an in vitro hypoxic
      model. Using confocal fluorescence microscopy, we showed that prolonged hypoxia
      (48h) induces mitochondrial fragmentation along with higher levels of the
      mitochondrial fission protein DRP1. Concomitantly, both mitochondrial potential
      and respiratory rates decreased, indicative of mitochondrial dysfunction. In
      accordance with a metabolic shift towards non-mitochondrial ATP generation, mRNA
      levels of glycolytic markers HK2, PFKFB2 and GLUT1 increased during hypoxia.
      Incubation of PASMC with TMZ, prior to hypoxia, prevented all these changes and
      precluded the increase in PASMC proliferation. These findings were also observed
      using Mdivi-1 (a pharmacological DRP1 inhibitor) or a dominant negative DRP1 K38A
      as pre-treatments. Altogether, our data indicate that TMZ exerts a protective
      role against hypoxia-induced PASMC proliferation, by preserving mitochondrial
      function, thus highlighting DRP1-dependent morphology as a novel therapeutic
      approach for diseases such as PAH.

PMID- 28739176
TI  - Digital rectal examination for prostate cancer screening performed with
      colonoscopy for colon cancer screening: 2 for the price of 1.

PMID- 28739175
TI  - Sudden infant death from neonate carnitine palmitoyl transferase II deficiency.
AB  - A full-term female baby born to parents who gave birth three years prior to a
      girl who survived only 31h postpartum died 36h after birth. An autopsy showed
      that the heart was markedly hypertrophic (32g). Microscopically, the myocardium,
      liver and kidney cells exhibited extensive vacuolar degeneration. Sudan III
      staining was positive in cardiac muscle, liver and kidney tissue. Tandem mass
      spectrometry analysis revealed that the deceased patient had a carnitine
      palmitoyl transferase II (CPT2) deficiency or a carnitine-acylcarnitine
      translocase deficiency. Genetic testing of the parents revealed heterozygous CPT2
      mutations, indicating that their offspring would have a 25% chance of having a
      CPT2 deficiency. Therefore, we speculated that CPT2 deficiency might be the cause
      of death based on the results of staining, tandem mass spectrometry analysis and
      parental genetic testing.

PMID- 28739177
TI  - Triterpenoids from the bark of Dysoxylum hainanense and their anti-inflammatory
      and radical scavenging activity.
AB  - A phytochemical investigation on the 70% EtOH extract of the bark of Dysoxylum
      hainanense resulted in the isolation of four new triterpenoids, dysoxyhaines A-D
      (1-4). Structural elucidation of all the compounds were performed by spectral
      methods such as 1D and 2D (1H1H COSY, HMQC, and HMBC) NMR spectroscopy, in
      addition to high resolution mass spectrometry. The isolated components were
      evaluated in vitro for anti-inflammatory activities for Cox-1 and Cox-2, and
      radical scavenging potential using ABTS.+ and DPPH test. As a result, nor seco
      olean type triterpenoid 1 exhibited significant anti-inflammatory potential,
      while tirucallane triterpenoids 3 and 4 showed radical scavenging activities.

PMID- 28739178
TI  - The role of health literacy in predicting adherence to nutritional
      recommendations: A systematic review.
AB  - OBJECTIVE: Synthesize quantitative empirical evidence on the role of health
      literacy in predicting adherence to dietary recommendations. METHODS: A
      systematic search of 13 online databases resulted in 1498 articles eligible for
      screening. Of those, 20 met the predefined inclusion criteria and, together with
      6 studies retrieved from their reference lists, were included for review.
      Screening of full-texts, data extraction and quality appraisal were independently
      performed by two reviewers. Inconsistencies regarding eligibility were resolved
      through discussion. RESULTS: Of the 26 reviewed articles, 17 involved patients
      and 9 the general population. Overall, 35 associations between health literacy
      and various nutrition behaviours were observed. A significant direct positive
      association was reported in 5 cases, all of them concerning the general
      population. An insignificant association was reported in 20 cases, 15 of which
      were related to patients. The remaining associations were negative (n=2),
      partially mediated (n=1) or entirely mediated (n = 7). CONCLUSION: Health
      literacy was scarcely determinant of dietary adherence and other nutrition
      behaviours, especially among patients. PRACTICE IMPLICATION: Patients' dietary
      adherence is likely to be unaffected by interventions based on health literacy.
      Empowering approaches are expected to be more beneficial.

PMID- 28739179
TI  - Emotion regulation contributes to the development of diabetes distress among
      adults with type 1 diabetes.
AB  - OBJECTIVE: To demonstrate how maladaptive emotion regulation (ER) can lead to
      diabetes distress (DD), with subsequent effects on management and metabolic
      outcomes among adults with type 1 diabetes. METHODS: Data are based on pre
      intervention assessment for a random controlled trial to reduce DD. Patients were
      recruited in California, Oregon, Arizona and Ontario, Canada. After screening and
      consent, patients completed an online assessment and released their most recent
      laboratory HbA1C. Structural equation modeling was used to define an ER
      measurement model and test for significant pathways. RESULTS: Three ER mechanisms
      combined into a single construct: emotion processing, non-judgment of emotions,
      non-reactivity to emotions. Models indicated a significant pathway from ER and
      cognitions to DD to disease management to metabolic control. CONCLUSIONS: As
      hypothesized, the three ER mechanisms formed a single, coherent ER construct.
      Patients with poor ER reported high DD; and high DD was linked to poor diabetes
      management and poor metabolic control. PRACTICE IMPLICATIONS: Identifying both
      the level of DD and the ER mechanisms that lead to high DD should be explored in
      clinical settings. Helping T1Ds to become more aware, less judgmental and less
      reactive behaviorally to what they feel about diabetes and its management may
      reduce DD.

PMID- 28739180
TI  - Uptake of mental health websites in primary care: Insights from an Australian
      longitudinal cohort study of depression.
AB  - OBJECTIVE: To describe the characteristics of primary care attendees with
      depressive symptoms who use mental health websites. METHODS: 789 individuals with
      depressive symptoms recruited and followed up annually for nine years. Self
      reported written surveys included mental health, professional and self-help use,
      e-mental health interventions or therapeutic websites. Marginal logistic
      regression examined association between mental health website (MHW) use and
      patient's mental health, health services use, anti-depressant use and self-help
      strategies. RESULTS: 36% of participants used an MHW at least once. MHW users
      were more likely to be female, younger, highly educated and employed. MHW use
      increased with depressive symptom severity; reported in 16% of assessments when
      minimal symptoms were present and 28% when severe symptoms were present. MHW use
      was associated with: GP mental health visits, psychologist and psychiatrist
      visits and other self-help strategies including self-help books and telephone
      helplines. CONCLUSION(S): Mental health websites were more likely to be used by
      those with severe depressive symptoms rather than those with mild depression as
      recommended in current guidelines. PRACTICE IMPLICATION(S): Whilst mental health
      websites offer potential to support the high volume of people with mild
      depression new strategies may be required to ensure uptake.

PMID- 28739182
TI  - Adolescents at Risk for Sexually Transmitted Infection Need More Than the Right
      Medicine.

PMID- 28739181
TI  - Delayed onset of ambulation in boys with Duchenne muscular dystrophy: Potential
      use as an endpoint in clinical trials.
AB  - Individuals with Duchenne muscular dystrophy (DMD) often exhibit delayed motor
      and cognitive development, including delayed onset of ambulation. Data on age
      when loss of independent ambulation occurs are well established for DMD; however,
      age at onset of walking has not been well described. We hypothesize that an
      effective medication given in early infancy would advance the age when walking is
      achieved so that it is closer to age-matched norms, and that this discrete event
      could serve as the primary outcome measure in a clinical trial. This study
      examined three data sets, Muscular Dystrophy Surveillance, Tracking, and Research
      Network (MD STARnet); Dutch Natural History Survey (DNHS); and Parent Project
      Muscular Dystrophy (PPMD). The distribution of onset of ambulation in DMD (mean
      +/- SD) and median age, in months, at the onset of ambulation was 17.3 (+/-5.5)
      and 16.0 in MD STARnet, 21.8 (+/-7.1) and 20.0 in DNHS, and 16.1 (+/-4.4) and 15
      in PPMD. Age of ambulation in these data sets were all significantly later (P
      <0.001) than the corresponding age for typically developing boys, 12.1 (+/-1.8).
      A hypothetical clinical trial study design and power analyses are presented based
      on these data.

PMID- 28739183
TI  - Can crosstalk between DOR and PARP reduce oxidative stress mediated
      neurodegeneration?
AB  - The progressive loss of structure and function of neurons leads to
      neurodegenerative processes which become the causative reason for various
      neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease
      (AD) etc. These diseases are multifactorial in nature but they have been seen to
      possess similar causative agents to a certain extent. Oxidative Stress (OS) has
      been identified as a major stressor and a mediator in most of these diseases. OS
      not only leads to the generation of free radical species but if persistent, can
      possibly lead to lipid peroxidation, protein damage, DNA damage, and cell death.
      Anti-oxidants are endogenously present in our body to tackle oxygen metabolites
      but their levels reduce greatly under continuous OS conditions. In such a case,
      dietary supplements to replenish the anti-oxidant levels in our body is a good
      way of treatment but it is very slow and may not be as effective in chronic
      stress conditions. Thus, there is a need for more effective mechanisms to
      attenuate OS. Two such mechanisms which can be considered are the activation of
      Delta opioid receptor (DOR) and Inhibition of Poly (ADP-ribose)-polymerase1
      (PARP1), which have been suggested to protect neurons and increase neuronal cell
      survivability in both in-vitro and in-vivo disease models. Various signaling
      pathways have been highlighted to probably play a significant role in attenuating
      OS by the activation of DOR. It would be an interesting topic of investigation to
      see if one of the probable mechanisms by which DOR attenuates OS could be by
      modulation of PARP through a cascade of intracellular signaling reactions.

PMID- 28739184
TI  - Carotid plaque instability is not related to quantity but to elemental
      composition of calcification.
AB  - BACKGROUND AND AIMS: Recent studies highlighted the role of calcification
      processes in the clinical progression of chronic cardiovascular diseases. In this
      study we investigated the relationship between the chemical composition of
      calcification and atherosclerotic plaque stability in carotid arteries. METHODS
      AND RESULTS: To this end, we characterized the calcification on 229 carotid
      plaques, by morphology, immunohistochemistry, transmission electron microscopy
      and energy dispersive X-ray microanalysis. Plaques were classified into two
      categories: unstable and stable. No significant differences were found in the
      incidence of the various risk factors between patients with and without carotid
      calcification, with the exception of diabetes. The energy dispersive X-ray
      microanalysis allowed us to identify two types of calcium salts in the
      atheromatous plaques, hydroxyapatite (HA) and calcium oxalate (CO). Our results
      showed that calcification is a common finding in carotid plaques, being present
      in 77.3% of cases, and the amount of calcium is not a factor of vulnerability.
      Noteworthy, we observed an association between HA calcification and unstable
      plaques. On the contrary, CO calcifications were mainly detected in stable
      plaques. CONCLUSIONS: The presence of different types of calcification in
      atheromatous plaques may open new perspectives in understanding the molecular
      mechanisms of atheroma formation and plaque instability.

PMID- 28739185
TI  - Novel atherogenic pathways from the differential transcriptome analysis of
      diabetic epicardial adipose tissue.
AB  - BACKGROUND AND AIM: To evaluate the epicardial adipose tissue (EAT) transcriptome
      in comparison to subcutaneous fat (SAT) in coronary artery disease (CAD) and type
      2 diabetes (T2DM). METHODS AND RESULTS: SAT and EAT samples were obtained from
      subjects with T2DM and CAD (n = 5) and those without CAD with or without T2DM
      (=3) undergoing elective cardiac surgery. RNA-sequencing analysis was performed
      in both EAT and SAT. Gene enrichment analysis was conducted to identify pathways
      affected by the differentially expressed genes. Changes of top genes were
      verified by quantitative RT-PCR (qRT-PCR), western blot, and immunofluorescence.
      A total of 592 genes were differentially expressed in diabetic EAT, whereas there
      was no obvious changes in SAT transcriptome between diabetics and non-diabetics.
      Diabetic EAT was mainly enriched in inflammatory genes, such as Colony
      Stimulating Factor 3 (CSF3), Interleukin-1b (IL-1b), IL-6. KEGG pathway analysis
      confirmed that upregulated genes were involved in inflammatory pathways, such as
      Tumor Necrosis Factor (TNF), Nuclear Factor-kappaB (NF-kappaB) and advanced
      glycation end-products-receptor advanced glycation end products (AGE-RAGE). The
      overexpression of inflammatory genes in diabetic EAT was largely correlated with
      upregulated transcription factors such as NF-kappaB and FOS. CONCLUSIONS:
      Diabetic EAT transcriptome is significantly different when compared to diabetic
      SAT and highly enriched with genes involved in innate immune response and
      endothelium, like Pentraxin3 (PTX3) and Endothelial lipase G (LIPG). EAT
      inflammatory genes expression could be induced by upregulated transcription
      factors, mainly NF-kB and FOSL, primarily activated by the overexpressed AGE-RAGE
      signaling. This suggests a unique and novel atherogenic pathway in diabetes.

PMID- 28739186
TI  - Epicardial fat thickness correlates with P-wave duration, left atrial size and
      decreased left ventricular systolic function in morbid obesity.
AB  - BACKGROUND AND AIM: Epicardial fat (EF) is increased in obesity and has important
      interactions with atrial and ventricular myocardium. Most of the evidence in this
      scenario can be confused by the presence of comorbidities such as hypertension,
      diabetes and dyslipidemia, which are very common in this population. The
      influence of EF on atrial remodeling and cardiac function demands further
      investigation on morbidly obese without these comorbidities. METHODS AND RESULTS:
      We prospectively recruited 20 metabolically healthy morbidly obese and 20 normo
      weights controls. The maximum P-wave duration (PWD) was analyzed by 12-lead
      electrocardiogram. Left atrial diameter (LAD), left ventricular ejection fraction
      (LVEF) and EF thickness (EFT) were evaluated by two-dimensional echocardiography.
      The mean of maximum PWD and LAD were significantly larger in the obese group as
      compared to the control group: 109.55 +/- 11.52 ms * 89.38 +/- 11.19 ms and 36.12
      +/- 3.46 mm * 31.45 +/- 2.64 mm, (p < 0.0001). The mean LVEF was lower in the
      obese group: 63.15 +/- 4.25% * 66.17 +/- 3.37% (p < 0.017). The mean EFT was
      higher in the obese group: 7.72 +/- 1.60 mm * 3.10 +/- 0.85 mm (p < 0.0001). A
      positive correlation was found between EFT and PWD (r = 0.70; p = 0.001) and LAD
      (r = 0.667; p = 0.001). An inverse correlation was found between EFT and LVEF (r
      = -0.523; p = 0.001). In a multiple multivariate regression analysis the EFT
      remains correlated with LAD and LVEF. CONCLUSIONS: In a select group of morbidly
      obese, the excess of EF had a significant impact on atrial remodeling and cardiac
      function.

PMID- 28739187
TI  - Fluidity of the dietary fatty acid profile and risk of coronary heart disease and
      ischemic stroke: Results from the EPIC-Netherlands cohort study.
AB  - BACKGROUND AND AIMS: The fluidity of dietary fatty acids consumed has been
      suggested to inversely affect coronary heart disease (CHD) risk. Lipophilic index
      (LI) represents overall fluidity of the dietary fatty acid profile. Lipophilic
      load (LL) represents a combination of overall fluidity and absolute intake of
      dietary fatty acids. We investigated the relations of dietary LI and LL with risk
      of CHD and ischemic stroke (iStroke). METHODS AND RESULTS: We used data from the
      prospective EPIC-NL study, including 36,520 participants aged 20-70 years. LI and
      LL were calculated using dietary intake data estimated with a validated FFQ.
      Incident CHD (n = 2348) and iStroke (n = 479) cases were obtained through linkage
      to national registers during 15 years follow-up. LI and LL were not associated
      with CHD risk (HRshighest-versus-lowest-quartiles: 0.93 [95%CI: 0.83, 1.04], and
      0.92 [95%CI: 0.79, 1.07], respectively), and neither with iStroke risk (HRs 1.15
      (95%CI: 0.89, 1.48), and 0.98 (95%CI: 0.70, 1.38), respectively). Original fatty
      acid classes (SFA, MUFA and PUFA), and LI and LL stratified by these fatty acid
      classes, were overall not related to CHD and ischemic stroke either. CONCLUSIONS:
      In this Dutch population, neither the overall fluidity of the dietary fatty acid
      profile (LI), nor the combined fluidity and amount of fatty acids consumed (LL)
      were related to CHD or iStroke risk. Dietary LI and LL may have limited added
      value above original fatty acid classes and food sources in establishing the
      relation of fatty acid consumption with CVD.

PMID- 28739188
TI  - The long-term relationship between dietary pantothenic acid (vitamin B5) intake
      and C-reactive protein concentration in adults aged 40 years and older.
AB  - BACKGROUND AND AIMS: Low-grade inflammation, represented by minor C-reactive
      protein (CRP) elevation, has a critical role in the early stages of
      atherosclerosis, and pantothenic acid (PA) may have an antioxidant effect in
      inflammatory process. However, the long-term relationship between PA intake and
      CRP has not yet been studied. The objective of the present study was to evaluate
      the long-term relationship of PA intake to CRP concentration in healthy adults
      aged 40 years or older living in a rural area of South Korea. METHODS AND
      RESULTS: A total of 908 subjects (349 men, 559 women) with repeated data on
      dietary PA intake and CRP concentration were included in the final analysis. To
      represent the long-term effect of PA intake, both PA intake at the baseline and
      average PA intake were used as the exposure, and CRP concentration at the third
      visit and its change from the baseline to the third visit were used as the
      outcome. After adjustment for potential confounders, a significant inverse
      relationship between PA intake and CRP concentration at the third visit was
      observed (P for trend = 0.001, beta = -0.07 (P-value = 0.001) for PA baseline; P
      for trend = <0.0001, beta = -0.11 (P-value = 0.0004) for PA average (baseline,
      2nd, 3rd)). Higher PA intake was significantly related to lower or attenuated
      increase in CRP concentration (P for trend = 0.002, beta = -0.24 (P-value =
      0.002) for PA baseline; P for trend = 0.001, beta = -0.35 (P-value = 0.001) for
      PA average (baseline, 2nd, 3rd)). CONCLUSIONS: In conclusion, dietary PA intake
      was inversely related to subsequent CRP concentration in both men and women aged
      40 years or older in South Korea.

PMID- 28739189
TI  - Endoscopic transcanal myringoplasty for tympanic perforations: An outpatient
      minimally invasive procedure.
AB  - OBJECTIVE: Since the 1950s, microscopic myringoplasty has been the standard
      surgery for repairing a perforated tympanic membrane. In addition to conventional
      microscopic myringoplasty, endoscopic myringoplasty has been an emerging
      technique since the late 1990s. This study evaluated the efficacy of endoscopic
      transcanal myringoplasty for repairing tympanic perforations and examined the
      minimally invasive feature of this technique (no postauricular incision, no
      canalplasty). METHODS: We retrospectively reviewed the medical records of
      patients who underwent endoscopic transcanal myringoplasty for perforations of
      the tympanic membrane. The main outcome was the overall rate of graft success of
      endoscopic transcanal myringoplasty. RESULTS: A total of 181 patients were
      included in the analysis. The overall graft success was determined in 163 of 181
      patients (92.8%). The mean preoperative and postoperative air-bone gaps were
      19.3dB and 7.8dB, respectively, revealing a significant improvement of 11.5dB
      (Cohen's d, 1.27; 95% CI, 1.03-1.50; P<0.05; paired t test) in the air-bone gap.
      The rate of graft success with partial visualization of the perforation margin
      was comparable to that with complete visualization of the perforation margin.
      Larger sizes of perforations were significantly associated with lower rates of
      graft success (P<0.01). CONCLUSION: Our study revealed that the rate of graft
      success and hearing results of endoscopic transcanal myringoplasty and
      microscopic myringoplasty are comparable for repairing perforations of the
      tympanic membrane. Visualization of the perforation margin by otoscopy did not
      affect the rate of graft success. However, endoscopic transcanal myringoplasty is
      less invasive because this technique does not require postauricular incision,
      canalplasty, and general anesthesia.

PMID- 28739190
TI  - The treatment and outcome analysis of primary squamous cell carcinoma of the
      thyroid.
AB  - OBJECTIVES: Primary squamous cell carcinoma (SCC) of the thyroid is a rare
      disease. It usually presents with locally advanced disease and has an overall
      poor prognosis. In this study, we investigated the characteristics and outcomes
      of patients with SCC of the thyroid, and reported our experience with
      chemotherapy with lenvatinib in the treatment of SCC of the thyroid. METHODS: The
      management outcome of 10 patients who had SCC of the thyroid between January 2000
      and 2015 at Kyushu University Hospital or associated facilities was reviewed.
      RESULTS: There were 3 males and 7 females, ranging in age from 53 to 77 years.
      Extent of disease was staged as follows: stage IVA, 3 cases; stage IVB, 3 cases;
      stage IVC, 4 cases. Only tracheostomy was applied for 2 cases, surgical
      resection, such as total thyroidectomy and neck dissection, for the other 8
      cases. Radiotherapy following surgical treatment was applied for 9 cases. Four
      patients started on oral lenvatinib due to recurrent or progressive SCC of the
      thyroid. The one year actuarial survival rate of patients was 22.7%. There was no
      2-year survivor of all patients. CONCLUSIONS: Treatment should primarily be
      targeted at surgical resection with negative margins in patients with resectable
      disease. Lenvatinib may show promise to potentially extend survival.

PMID- 28739191
TI  - Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody,
      prevents skin xenograft rejection in humanized mice.
AB  - Oral administration of biologics may be a feasible approach for immune therapy
      that improves drug safety and potentiates mechanisms of tolerance at mucosal
      barriers. We tested the ability of a fully human non-FcR binding anti-CD3 mAb,
      foralumab, to prevent skin xenograft rejection in mice with human immune systems.
      At an intragastric dose of 15MUg, the drug could transit through the small bowel.
      Serum absorption and binding of lymphoid cells was seen and proliferative
      responses of splenic CD8+ T cells to mitogen were reduced. Five consecutive daily
      doses, then weekly dosing led to indefinite graft acceptance without depletion of
      peripheral T cells. Proliferative and cytokine responses to activation of
      splenocytes with PHA were reduced. The serum levels of IL-10 but not TNF were
      increased 6days after application of the skin graft. Oral treatment with anti-CD3
      mAb may represent a feasible approach for immune modulation.

PMID- 28739192
TI  - Fine needle aspiration for the diagnosis and treatment of musculoskleletal
      tumours.
AB  - OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of FNA
      and analyse its efficacy in enabling the initiation of treatment in
      musculoskeletal tumours. METHODS: A total of 130 FNA were performed (94 bone and
      36 soft tissue lesions) guided by CT scan (n = 64), ultrasonography (n = 36) and
      radioscopy (n = 30). Diagnostic yield and accuracy were evaluated. A diagnosis
      was considered accurate when confirmed by histology or ulterior clinical/imaging
      evaluation. Exclusion of malignancy or infection was considered as diagnoses.
      RESULTS: Ninety diagnoses (69.2%) were obtained: 87 (96.7%) were accurate and 3
      were wrong. FNA was non-diagnostic in 40 cases (30.8%) but in 15 (11.5%) it has
      been possible to conclude if the lesion was malignant (n = 6) or benign (n = 9).
      This method was completely inconclusive in 25 cases (19.2%). CONCLUSION: Despite
      the low diagnostic yield, accuracy was high. FNA allowed the initiation of
      treatment in all 87 patients with a correct diagnosis and in 9 in which
      malignancy was excluded. Two of the 6 biopsies with the information of malignancy
      were soft tissue lesions. Even here, treatment could be done, as the majority of
      soft tissue sarcoma protocols begin with surgery. This study validates FNA as a
      method with a high diagnostic accuracy.

PMID- 28739193
TI  - Intraocular metastasis: comparison of clinical presentation with a known and
      unknown primary tumour.
AB  - OBJECTIVE: The purpose of the present study is to review the frequency of
      intraocular metastases as first presentation of systemic disease, and to identify
      clinical and tumour characteristics. METHODS: Retrospective study of consecutive
      cases diagnosed of intraocular metastasis at a referral intraocular tumours unit
      between 1993 and 2014. General, epidemiological and ophthalmological
      characteristics were recorded. RESULTS: A total of 21 patients, with a mean age
      62.7 years (31-89) were diagnosed with intraocular metastasis between 1993 and
      2014. Both eyes were affected in 4 cases. Location was choroid in 20 cases. The
      intraocular tumour was the first manifestation of the systemic disease in 13
      patients (61.9%). Primary tumour was breast in 47.6% and lung in 23.8%. Diagnosis
      of the primary tumour was performed by systemic studies, and only 1 patient
      required intraocular biopsy. Regarding the treatment, the majority of cases were
      controlled with systemic therapy, with 4 cases requiring additional external beam
      radiotherapy, and only one enucleation. No clinical differences were found
      between the cases with known and unknown systemic neoplasia, except in exudative
      retinal detachment, which was more frequent in the second group. CONCLUSIONS:
      Although intraocular metastases are the most frequent intraocular tumour, they
      are not a frequent cause of consultation. In more than half of the cases it is
      the first presentation of unknown systemic neoplasia as a solitary non-pigmented
      intraocular mass. Early diagnosis is crucial to establish the appropriate
      treatment, preserve visual function, and improve the prognosis of the patient.

PMID- 28739194
TI  - Perforator based rectus free tissue transfer for head and neck reconstruction:
      New reconstructive advantages from an old friend.
AB  - OBJECTIVES: To demonstrate three reconstructive advantages of the perforator
      based rectus free tissue transfer: long pedicle, customizable adipose tissue, and
      volume reconstruction without muscle atrophy within a contained space. MATERIALS
      AND METHODS: Thirty patients with defects of the head and neck were reconstructed
      with the perforator based rectus free tissue transfer. RESULTS: Transplant
      success was 93%. Mean pedicle length was 13.4cm. Eleven patients (37%) had vessel
      poor necks and the long pedicle provided by this transplant avoided the need for
      vein grafts in these patients. Adipose tissue was molded in 17 patients (57%).
      Twenty-five patients (83%) had defects within a contained space, such as the
      orbit, where it was critical to have a transplant that avoided muscle atrophy.
      CONCLUSIONS: The perforator based rectus free tissue transfer provides a long
      pedicle, moldable fat for flap customization, and is useful in reconstruction of
      defects within a contained space where volume loss due to muscle atrophy is
      prevented.

PMID- 28739195
TI  - Dizziness Symptom Type Prevalence and Overlap: A US Nationally Representative
      Survey.
AB  - BACKGROUND: The traditional approach to dizziness encourages providers to
      emphasize the type of dizziness. However, symptom types might substantially
      overlap in individual patients, thus limiting the clinical value of this
      approach. We aimed to describe the overlap of types of dizziness using a US
      nationally representative sample. METHODS: The 2008 US National Health Interview
      Survey was examined for prevalence and overlap of types of dizziness. The data
      were also separately examined among people who otherwise had typical features of
      traditionally vertigo-based disorders (ie, benign paroxysmal positional vertigo
      and Meniere's disease). Data analysis also included exploratory factor analysis.
      RESULTS: Twelve-month prevalence of problems with dizziness or balance was 14.8%,
      representing 33.4 million individuals. The mean number of dizziness symptoms was
      2.4 (95% confidence interval [CI], 2.3-2.4), with 61.1% reporting more than one
      type. Of subjects who otherwise had typical features of traditionally vertigo
      based disorders, the mean number of dizziness types was 3.1 (95% CI, 3.0-3.3),
      and only 24.6% (95% CI, 21.0%-28.7%) reported vertigo as the primary type.
      Exploratory factor analysis found that symptom types loaded onto a single factor
      without other clinical or demographic variables. CONCLUSIONS: Substantial overlap
      of dizziness types exists among US adults with dizziness. People otherwise having
      features of traditionally vertigo-based disorders also typically report multiple
      dizziness types and do not typically report vertigo as the primary type. Symptom
      types correlate more strongly with each other than with other clinical or
      demographic variables. These findings suggest that the traditional emphasis on
      dizziness types is likely of limited clinical utility.

PMID- 28739196
TI  - Developing Optimized Treatment Plans for Patients with Dyslipidemia in the Era of
      Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapeutics.
AB  - This educational content was derived from a live satellite symposium at the
      American College of Physicians Internal Medicine Meeting 2017 in San Diego,
      California (online at http://courses.elseviercme.com/acp/702e). This activity
      will focus on optimized treatment plans for patients with dyslipidemia in the era
      of proprotein convertase subtilisin/kexin type 9 inhibitor therapeutics. Low
      density lipoprotein cholesterol has been identified as an important therapeutic
      target to prevent the progression of atherosclerotic disease; however, only 1 of
      every 3 adults with high low-density lipoprotein cholesterol has the condition
      under control. Expert faculty on this panel will discuss the science of
      proprotein convertase subtilisin/kexin type 9 inhibitors and aid physicians in
      the best practices to achieve low-density lipoprotein cholesterol target in their
      patients.

PMID- 28739197
TI  - Type 1 and 2 Myocardial Infarction and Myocardial Injury: Clinical Transition to
      High-Sensitivity Cardiac Troponin I.
AB  - BACKGROUND: Studies addressing patients with type 2 myocardial infarction and
      myocardial injury, including the impact of using high-sensitivity (hs) cardiac
      troponin (cTn) assays on their incidence are needed. METHODS: Ours is a
      prospective, observational US cohort study. Consecutive emergency department
      patients with serial cTnI measurements were studied. Outcomes included 180-day
      mortality and major adverse cardiac events, including 2-year follow-up for those
      with myonecrosis. RESULTS: Among 1640 patients, using a contemporary cTnI assay,
      30% (n = 497) had >=1 cTnI >99th percentile, with 4.7% (n = 77), 8.5% (n = 140),
      and 17% (n = 280) classified as type 1 myocardial infarction, type 2 myocardial
      infarction, and myocardial injury, respectively. Compared with patients without
      myonecrosis, 180-day mortality was higher for type 2 myocardial infarction (4% vs
      13%, P < .0001) (adjusted hazard ratio 2.7; 95% confidence interval, 1.6-4.8; P =
      .0005) and myocardial injury (4% vs 11%, P < .0001) (adjusted hazard ratio 1.8;
      95% confidence interval, 1.1-3.0; P = .02), both with mortality >20% at 2 years.
      Predictors of 2-year mortality for type 2 myocardial infarction included age,
      congestive heart failure, and beta-blockers. Relative to the contemporary cTnI
      assay, hs-cTnI had less myonecrosis (30% vs 26%, P = .003) and acute myocardial
      infarction (13.2% vs 10.8%, P = .032), including fewer type 2 myocardial
      infarctions (8.5% vs 6.3, P = .01), with no difference in myocardial injury (17%
      vs 15%, P = .1). CONCLUSIONS: cTnI increases are encountered in approximately a
      third of patients, the majority due to nonatherothrombotic conditions. Compared
      with patients without myonecrosis, type 2 myocardial infarction and myocardial
      injury have worse short-term outcomes, with mortality rates >20% at 2 years. hs
      cTnI assay does not lead to more myocardial injury or infarction.

PMID- 28739198
TI  - Efficacy and Safety of Apixaban Versus Warfarin in Patients with Atrial
      Fibrillation and a History of Cancer: Insights from the ARISTOTLE Trial.
AB  - BACKGROUND: Cancer is associated with a prothrombotic state and increases the
      risk of thrombotic events in patients with atrial fibrillation. We described the
      clinical characteristics and outcomes and assessed the safety and efficacy of
      apixaban versus warfarin in patients with atrial fibrillation and cancer in the
      Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial
      Fibrillation (ARISTOTLE) trial. METHODS: The association between cancer and
      clinical outcomes was assessed using Cox regression models. At baseline, 1236
      patients (6.8%) had a history of cancer; 12.7% had active cancer, and 87.3% had
      remote cancer. RESULTS: There were no significant associations between history of
      cancer and stroke/systemic embolism, major bleeding, or death. The effect of
      apixaban versus warfarin for the prevention of stroke/systemic embolism was
      consistent among patients with a history of cancer (event/100 patient-years = 1.4
      vs 1.2; hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.53-2.26) and no
      cancer (1.3 vs 1.6; HR, 0.77; 95% CI, 0.64-0.93) (P interaction = .37). The
      safety and efficacy of apixaban versus warfarin were preserved among patients
      with and without active cancer. Apixaban was associated with a greater benefit
      for the composite of stroke/systemic embolism, myocardial infarction, and death
      in active cancer (HR, 0.30; 95% CI, 0.11-0.83) versus without cancer (HR, 0.86;
      95% CI, 0.78-0.95), but not in remote cancer (HR, 1.46; 95% CI, 1.01-2.10)
      (interaction P = .0028). CONCLUSIONS: Cancer was not associated with a higher
      risk of stroke. The superior efficacy and safety of apixaban versus warfarin were
      consistent in patients with and without cancer. Our positive findings regarding
      apixaban use in patients with atrial fibrillation and cancer are exploratory and
      promising, but warrant further evaluation.

PMID- 28739199
TI  - Results of the First American Prospective Study of Intravenous Iron in Oral Iron
      Intolerant Iron-Deficient Gravidas.
AB  - BACKGROUND: Anemia affects up to 42% of gravidas. Neonatal iron deficiency is
      associated with low birth weight, delayed growth and development, and increased
      cognitive and behavioral abnormalities. While oral iron is convenient, up to 70%
      report significant gastrointestinal toxicity. Intravenous iron formulations
      allowing replacement in one visit with favorable side-effect profiles decrease
      rates of anemia with improved hemoglobin responses and maternal fetal outcomes.
      METHODS: Seventy-four oral iron-intolerant, second- and third-trimester iron
      deficient gravidas were questioned for oral iron intolerance and treated with
      intravenous iron. All received 1000 mg of low-molecular-weight iron dextran in
      250 mL normal saline. Fifteen minutes after a test dose, the remainder was
      infused over the balance of 1 hour. Subjects were called at 1, 2, and 7 days to
      assess delayed reactions. Four weeks postinfusion or postpartum, hemoglobin
      levels and iron parameters were measured. Paired t test was used for hemoglobin
      and iron; 58/73 women were questioned about interval growth and development of
      their babies. RESULTS: Seventy-three of 74 enrolled subjects completed treatment.
      Sixty had paired pre- and posttreatment data. The mean pre- and posthemoglobin
      concentrations were 9.7 and 10.8 g/dL (P < .00001), transferrin saturations 11.7%
      and 22.6% (P = .0003), and ferritins 14.5 and 126.3 ng/mL, respectively (P <
      .000001). Six experienced minor infusion reactions. All resolved. Data for 58
      infants were available; one was low on its growth charts for 11 months. The
      remaining 57 were normal. None were diagnosed with iron deficiency anemia.
      CONCLUSION: Intravenous iron has less toxicity and is more effective, supporting
      moving it closer to frontline therapy.

PMID- 28739200
TI  - Aortic Dissection and Aortic Aneurysms Associated with Fluoroquinolones: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Our objective was to evaluate the association between fluoroquinolone
      use and aortic dissection or aortic aneurysm in a systematic review and meta
      analysis. METHODS: We searched Medline, Embase, and Scopus from inception to
      February 15, 2017. We selected controlled studies for inclusion if they reported
      data on aortic dissection and aortic aneurysm associated with fluoroquinolones
      exposure versus no exposure. Data were extracted by 2 independent reviewers, with
      disagreements resolved through further discussion. We assessed the quality of
      studies using the Newcastle-Ottawa Scale for observational studies and the
      strength of evidence using the Grading of Recommendations Assessment,
      Development, and Evaluation approach. The odds ratios (ORs) from observational
      studies were pooled using the fixed-effect inverse variance method, and
      statistical heterogeneity was assessed using the I2 statistic. RESULTS: After a
      review of 714 citations, we included 2 observational studies in the meta
      analysis. Current use of fluoroquinolones was associated with a statistically
      significantly increased risk of aortic dissection (OR, 2.79; 95% confidence
      interval [CI], 2.31-3.37; I2 = 0%) and aortic aneurysm (OR, 2.25; 95% CI, 2.03
      2.49; I2 = 0%) in a fixed-effects meta-analysis. The unadjusted OR estimates and
      sensitivity analysis using a random-effects model showed similar results. We
      rated the strength of evidence to be of moderate quality. The number needed to
      treat to harm for aortic aneurysm for elderly patients aged more than 65 years
      who were current users of fluoroquinolones was estimated to be 618 (95% CI, 518
      749). CONCLUSIONS: Evidence from a small number of studies suggests that exposure
      to fluoroquinolones is consistently associated with a small but significantly
      increased risk of aortic dissection and aortic aneurysm.

PMID- 28739202
TI  - The relationship between dietary intake, growth and body composition in
      Phenylketonuria.
AB  - AIM: Phenylketonuria (PKU) is an inborn error of protein metabolism that results
      from perturbation in phenylalanine hydroxylase activity leading to elevated blood
      levels of phenylalanine (phe). We aimed to explore the relationships between
      dietary patterns (total-protein, natural-protein, amino-acid formula), and the
      ratio of protein to energy intake with growth and body composition. METHOD:
      Longitudinal prospective data (1-6 measurements) of growth, dietary intake and
      body composition in patients treated with phe-restricted diet only (D-PKU; n=32),
      and tetrahydrobiopterin (BH4)+/-phe-restricted diet (BH4-PKU; n=5) were collected
      over a two-year period. Healthy siblings provided control data (n=21). RESULTS:
      There were no significant differences in weight-, height-, BMI z-score or percent
      body fat mass (%fatmass) between the D-PKU, BH4-PKU and control groups or between
      the all-types of PKU combined and controls, which confirmed 'normal' growth in
      the PKU cohort. Total-protein intake in the all-types of PKU group met or
      exceeded WHO safe protein recommendations. There were no significant
      relationships between anthropometric and dietary variables. Significant negative
      correlations were found in body composition: %fatmass and total-protein intake
      (rs=-0.690, p<=0.001), natural-protein intake (rs=-0.534, p=0.001), and AAF
      intake (rs=-0.510, p=0.001). Age was significantly correlated with %fatmass
      (rs=0.493, p=0.002) A total-protein intake of 1.5-2.6g/kg/day and natural-protein
      intake >0.5g/kg/day were associated with improved body composition. An apparent
      safe P:E ratio of 3.0-4.5g protein/100kcal was strongly associated with
      appropriate growth outcomes. CONCLUSIONS: Clinical decision-making needs to
      consider both the enhancement of natural-protein tolerance and the application of
      an apparent 'safe' protein to energy ratio to support optimal growth and body
      composition in PKU.

PMID- 28739201
TI  - Neonatal detection of Aicardi Goutieres Syndrome by increased C26:0
      lysophosphatidylcholine and interferon signature on newborn screening blood
      spots.
AB  - BACKGROUND: Aicardi Goutieres Syndrome (AGS) is a heritable interferonopathy
      associated with systemic autoinflammation causing interferon (IFN) elevation,
      central nervous system calcifications, leukodystrophy and severe neurologic
      sequelae. An infant with TREX1 mutations was recently found to have abnormal
      C26:0 lysophosphatidylcholine (C26:0 Lyso-PC) in a newborn screening platform for
      X-linked adrenoleukodystrophy, prompting analysis of this analyte in
      retrospectively collected samples from individuals affected by AGS. METHODS: In
      this study, we explored C26:0 Lyso-PC levels and IFN signatures in newborn blood
      spots and post-natal blood samples in 19 children with a molecular and clinical
      diagnosis of AGS and in the blood spots of 22 healthy newborns. We used
      Nanostring nCounterTM for IFN-induced gene analysis and a high-performance liquid
      chromatography with tandem mass spectrometry (HPLC MS/MS) newborn screening
      platform for C26:0 Lyso-PC analysis. RESULTS: Newborn screening cards from
      patients across six AGS associated genes were collected, with a median disease
      presentation of 2months. Thirteen out of 19 (68%) children with AGS had
      elevations of first tier C26:0 Lyso-PC (>0.4MUM), that would have resulted in a
      second screen being performed in a two tier screening system for X-linked
      adrenoleukodystrophy (X-ALD). The median (95%CI) of first tier C26:0 Lyso-PC
      values in AGS individuals (0.43MUM [0.37-0.48]) was higher than that seen in
      controls (0.21MUM [0.21-0.21]), but lower than X-ALD individuals (0.72MUM [0.59
      0.84])(p<0.001). Fourteen of 19 children had elevated expression of IFN signaling
      on blood cards relative to controls (Sensitivity 73.7%, 95%CI 51-88%, Specificity
      95%, 95% CI 78-99%) including an individual with delayed disease presentation
      (36months of age). All five AGS patients with negative IFN signature at birth had
      RNASEH2B mutations. Consistency of agreement between IFN signature in neonatal
      and post-natal samples was high (0.85). CONCLUSION: This suggests that
      inflammatory markers in AGS can be identified in the newborn period, before
      symptom onset. Additionally, since C26:0 Lyso-PC screening is currently used in X
      ALD newborn screening panels, clinicians should be alert to the fact that AGS
      infants may present as false positives during X-ALD screening.

PMID- 28739203
TI  - [Odontoid fracture in an elderly patient: a case report].

PMID- 28739204
TI  - Materials and Methods.

PMID- 28739205
TI  - Henry and Mount Rushmore.

PMID- 28739206
TI  - Hyperhidrosis caused by deep brain stimulation in the posterior subthalamic area.

PMID- 28739207
TI  - Obstructive Sleep Apnea and Hallmarks of Aging.
AB  - Obstructive sleep apnea (OSA) is one of the most common sleep disorders. Since
      aging is a risk factor for OSA development, it is expected that its prevalence
      will increase with the current increase in life span. In recent years, several
      studies have shown that OSA potentially contributes to functional decline, mainly
      prompted by chronic intermittent hypoxia and sleep fragmentation. Here, we
      propose that OSA might anticipate/aggravate aging by inducing cellular and
      molecular impairments that characterize the aging process, such as stem cell
      exhaustion, telomere attrition and epigenetic changes. We suggest that further
      knowledge on the impact of OSA on aging mechanisms might contribute to a better
      understanding of how OSA might putatively accelerate aging and aging-related
      diseases.

PMID- 28739208
TI  - Sleepiness in subjects with possible attention-deficit hyperactivity disorder.

PMID- 28739209
TI  - Analytical and biological variation in repeated sweat chloride concentrations in
      clinical trials for CFTR modulator therapy.
AB  - BACKGROUND: Using sweat chloride as a biomarker for CFTR modifying drugs requires
      knowledge of analytical and biological variation. METHODS: 979 sweat chloride
      concentrations from 128 subjects enrolled in the placebo arm of 2 multicenter,
      investigational drug trials were analyzed to determine coefficients of variation
      (CV) as well as reference change value (RCV) and index of individuality (II).
      RESULTS: For these populations, calculated values for the two studies were:
      analytical variation (3.9, 4.1%); within-subject variation (4.4, 6.0%); between
      subject variation (8.9, 7.0%); RCV (13.7, 17.0%) and II (0.7, 1.0). Sweat
      chloride variation was not affected by sex, collection site or sample weight; but
      was slightly affected by age in one of the two studies. CONCLUSION: Through
      determination of analytical as well as between- and within-subject variation, and
      with a larger sample size, our data allows improved estimates of the RCV and II,
      and can contribute to future trials of CFTR modulators and inform the design and
      interpretation of n of 1 trials in both research and clinical settings.

PMID- 28739210
TI  - Bile salt stimulated lipase: Inhibition by phospholipids and relief by
      phospholipase A2.
AB  - INTRODUCTION: Bile salt stimulated lipase (BSSL; Enzyme Commission (EC) number
      3.1.1.13) has been a candidate triglyceridase for improving enzyme therapy for
      pancreatic insufficiency; however, its efficacy is near absent. We hypothesise
      that similarly to pancreatic lipase, BSSL is inhibited by phospholipids and this
      inhibition is relieved by Phospholipase A2 (PLA2; EC 3.1.1.4), and the present
      study was undertaken to explore this possibility. MATERIALS AND METHODS:
      Synthetic emulsions of triglyceride and phosphatidylcholine (PC) or
      lysophosphatidylcholine (LPC)/bile salt mixed micelles were used as a model of
      intestinal digestion-media. The effect of PLA2 treatment of systems containing PC
      on BSSL activity was also explored. Automatic titration at constant pH (pH-stat)
      and nuclear magnetic resonance (NMR) spectroscopy were used to measure the rate
      and identify products of lipolysis. RESULTS: PC was inhibitory to BSSL activity,
      while LPC became inhibitory only above an LPC/bile salt concentration ratio of
      0.3. PLA2 treatment relieved the inhibition only below this ratio, despite its
      complete phospholipid-hydrolysing action. Thus, LPC had an inhibitory effect at
      higher concentrations. CONCLUSIONS: These results may implicate a change in the
      design of enzyme therapy in patients with pancreatic exocrine insufficiency.
      Supplementation of BSSL with PLA2 could improve patient health with adequate
      manipulation of phospholipid and lysophospholipid concentrations in the
      intestinal fluid.

PMID- 28739211
TI  - Investigating the surface dose contribution of intrafractional kV imaging in
      CyberKnife-based stereotactic radiosurgery.
AB  - CyberKnife treatment consists of hundreds of noncoplanar beams and numerous
      intrafractional images that can be taken during a single treatment fraction;
      thus, doses because of imaging should be considered in this technique. The aim of
      this study is to investigate the in-field and out-of-field surface doses induced
      from kV imaging system during stereotactic radiosurgery (SRS) treatment. The
      imaging-induced surface doses were measured at the center of the imaging field
      and within +/-15-cm distance from the center in both craniocaudal and lateral
      directions. TLD100H thermoluminescence dosimeters and EBT2 gafchromic films were
      used to take the measurements at the locations of 0, +/-5, +/-10, and +/-15 cm in
      the 2 orthogonal directions on abdominal region of a Rando phantom. The surface
      dose contributions of imaging system for the 4 most commonly used energy options
      of 90, 100, 110, and 120 kVp with 3 mAs options of 10, 30, and 90 mAs were
      measured and compared. Imaging dose values have a positive correlation with both
      parameters of energy and mAs. The energy options of 100, 110, and 120 kVp, in
      average, induced 60%, 101%, and 141% more doses per mAs than 90 kVp energy in the
      imaging field center. A threefold increase in mAs values, i.e., from 10 mAs to 30
      mAs and from 30 mAs to 90 mAs, caused higher dose in field center with a factor
      of 2.53 +/- 0.08 when the energy value was kept constant. The in-field dose
      distributions within +/-10 cm in both directions showed a flat pattern with a
      standard deviation lower than 5%, whereas the out-of-field doses at +/-15-cm
      distance from the field center suddenly dropped to almost half of the central
      doses. Although a single imaging attempt causes a very low dose compared with the
      therapeutic dose level, one should be aware of the cumulative surface dose
      increase with higher imaging number. Proper patient setup, fiducial usage, and
      reduction of both the mAs values and the imaging numbers should be, therefore,
      considered to keep the cumulative surface dose in a lower level.

PMID- 28739212
TI  - Conference Programme: 45th Annual Conference of the European Teratology.

PMID- 28739214
TI  - Influence of platelet count, platelet mass index, and platelet function on the
      spontaneous closure of ductus arteriosus in the prematurity.
AB  - BACKGROUND: This study aims at evaluating the influence of platelet count,
      platelet mass index, and platelet function on the spontaneous closure of ductus
      arteriosus in prematurity. METHODS: All preterm babies were divided into two
      groups, including Group 1 with "open PDA" and Group 2 with "closed PDA". The
      variables of platelet count, mean platelet volume, platelet mass index, and
      platelet function were analyzed and compared between two groups of patients to
      identify the factors that significantly influenced spontaneous closure of ductus
      arteriosus. RESULTS: Twenty-four patients were in the "open PDA" group, whereas
      36 patients were in the "closed PDA" group. Mean GA and BW were 27.6 +/- 1.8
      (23.1-30.4) and 28 +/- 1.6 (23.4-30.6) weeks and 1009 +/- 270 (585-1480) g and
      1035 +/- 298 (505-1500) g in "open PDA" and "closed PDA" groups, respectively (p
      > 0.05). The incidence of "Collagen-ADP > 130 s" was significantly higher in the
      "open PDA" group, and the levels of hemoglobin and hematocrit were significantly
      lower in the "open PDA" group (p < 0.05). Multivariate logistic regression
      analysis showed that respiratory distress syndrome (OR: 9, CI: 1.5-51.8) and
      collagen-ADP > 130 s (OR: 5.7 CI: 1.55-21.3) are two independent factors
      associated with ductal patency. CONCLUSION: This is the first study in the
      English literature providing evidence of the influence of platelet dysfunction on
      the spontaneous closure of ductus arteriosus in prematurity. Longer collagen-ADP
      duration is identified as a risk factor of ductal closure.

PMID- 28739213
TI  - Association Between Substance Use Disorder and Polygenic Liability to
      Schizophrenia.
AB  - BACKGROUND: There are high levels of comorbidity between schizophrenia and
      substance use disorder, but little is known about the genetic etiology of this
      comorbidity. METHODS: We tested the hypothesis that shared genetic liability
      contributes to the high rates of comorbidity between schizophrenia and substance
      use disorder. To do this, polygenic risk scores for schizophrenia derived from a
      large meta-analysis by the Psychiatric Genomics Consortium were computed in three
      substance use disorder datasets: the Collaborative Genetic Study of Nicotine
      Dependence (ascertained for tobacco use disorder; n = 918 cases; 988 control
      subjects), the Collaborative Study on the Genetics of Alcoholism (ascertained for
      alcohol use disorder; n = 643 cases; 384 control subjects), and the Family Study
      of Cocaine Dependence (ascertained for cocaine use disorder; n = 210 cases; 317
      control subjects). Phenotypes were harmonized across the three datasets and
      standardized analyses were performed. Genome-wide genotypes were imputed to the
      1000 Genomes reference panel. RESULTS: In each individual dataset and in the mega
      analysis, strong associations were observed between any substance use disorder
      diagnosis and the polygenic risk score for schizophrenia (mega-analysis pseudo-R2
      range 0.8-3.7%; minimum p = 4 * 10-23). CONCLUSIONS: These results suggest that
      comorbidity between schizophrenia and substance use disorder is partially
      attributable to shared polygenic liability. This shared liability is most
      consistent with a general risk for substance use disorder rather than specific
      risks for individual substance use disorders and adds to increasing evidence of a
      blurred boundary between schizophrenia and substance use disorder.

PMID- 28739215
TI  - [Histoseminar on inflammatory bowel diseases (IBD). Introduction - pathologist's
      role in diagnosis and surveillance in 2017].

PMID- 28739216
TI  - [Histoseminar on inflammatory bowel diseases (IBD): Case no 03].

PMID- 28739217
TI  - [Histoseminar on inflammatory bowel diseases (IBD): Cases no 05 and 06].

PMID- 28739218
TI  - Phase Behavior of an Fc-Fusion Protein Reveals Generic Patterns of Ion-Specific
      Perturbation on Protein-Protein Interactions.
AB  - Modulation of phase separation temperature (Tph) for liquid-liquid phase
      separation of an Fc-fusion protein was studied at pH values below, near, and
      above its pI where the net charge of the protein was positive, neutral, and
      negative, respectively, in KF, KCl, KSCN, and MgCl2 solutions. At the pH value
      near the pI, the monotonic drop in Tph for all the salt solutions suggests that
      both the anion and cation can disrupt attractive protein-protein interactions,
      effectively salting-in the protein. At the pH below or above the pI, the counter
      ion neutralizes the net charge on the protein. The neutralization reduces
      repulsive protein-protein interactions while the co-ion effectively strengthens
      them. Then, salting-in behavior appears after the completion of charge
      neutralization. Last, the complex ion-specific modulation on Tph could be
      rationalized through the rankings of SCN- > Cl- > F- and Mg2+ > K+ for their
      interactions with the protein throughout the pH conditions.

PMID- 28739219
TI  - Systematic review of hardware-related complications of Deep Brain Stimulation: Do
      new indications pose an increased risk?
AB  - INTRODUCTION: Deep Brain Stimulation (DBS) is an effective treatment extended
      broadly to many neurological and psychiatric disorders. Nevertheless,
      complications may arise during DBS procedures or following implantation due to
      implanted hardware. This may result in both minor and major adverse events that
      may necessitate hardware removal and/or compromise maximal therapeutic benefit
      for the patient. OBJECTIVES AND METHODS: To identify relevant literature on
      hardware-related complications from DBS procedures by performing a systematic
      review, and propose how to identify at-risk group and possible preventive
      approaches. RESULTS: Of 4592 abstract screened, 96 articles fulfilled the
      selection criteria and were reviewed. Overall, the most common hardware-related
      complications were infections (5.12% of patients), followed by lead migration
      (1.60%), fracture or failure of the lead or other parts of the implant (1.46% and
      0.73%, respectively), IPG malfunctions (1.06% of patients), and skin erosions
      without infections (0.48% of patients). New indications for DBS, including
      Tourette's syndrome, cluster headache, and refractory partial epilepsy, were
      found to bear a higher incidence of hardware-related infections than established
      indications such as Parkinson's disease. The highest rate of lead fracture or
      failure was found in dystonia patients (4.22%). Ultimately, the highest rate of
      pain at the implantation sites was found in refractory partial epilepsy patients
      (16.55%). CONCLUSION: Our analysis identified a variety of potential hardware
      related complications among patients who underwent DBS procedures. Patients who
      were at risk of complications, such as patients with dystonia and off-label
      indications (e.g. Tourette's syndrome) should be informed prior to surgery and
      closely followed thereafter.

PMID- 28739220
TI  - Beyond Native Cas9: Manipulating Genomic Information and Function.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR)-mediated
      manipulation of genomic information is becoming more versatile by combining
      nuclease-deficient CRISPR systems with a wide variety of effectors including base
      editing deaminases, transcriptional regulators, and epigenetic modifiers. The
      programmable binding ability of CRISPR systems is essential when the systems are
      employed as targeting domains to recruit the effectors to specific genomic loci.
      The discovery of a variety of Cas9 orthologs and engineered variants enables high
      fidelity genome editing and a wider selection of genomic targets, and CRISPR
      mediated deaminases enable more precise and predictable genome editing compared
      with CRISPR nuclease-based editing. Finally, combining transcriptional regulators
      with CRISPR systems can control expression of specific genes in a genome. Some
      applications and future challenges of CRISPR-derived tools are also discussed.

PMID- 28739221
TI  - Structure and Computation in Immunoreagent Design: From Diagnostics to Vaccines.
AB  - Novel immunological tools for efficient diagnosis and treatment of emerging
      infections are urgently required. Advances in the diagnostic and vaccine
      development fields are continuously progressing, with reverse vaccinology and
      structural vaccinology (SV) methods for antigen identification and structure
      based antigen (re)design playing increasingly relevant roles. SV, in particular,
      is predicted to be the front-runner in the future development of diagnostics and
      vaccines targeting challenging diseases such as AIDS and cancer. We review state
      of-the-art methodologies for structure-based epitope identification and antigen
      design, with specific applicative examples. We highlight the implications of such
      methods for the engineering of biomolecules with improved immunological
      properties, potential diagnostic and/or therapeutic uses, and discuss the
      perspectives of structure-based rational design for the production of advanced
      immunoreagents.

PMID- 28739222
TI  - Biomarkers of cancer cachexia.
AB  - Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal
      muscle and fat mass, which affects the majority of advanced cancer patients and
      is associated with poor prognosis. Interestingly, reversing muscle loss in animal
      models of cancer cachexia leads to prolong survival. Therefore, detecting
      cachexia and maintaining muscle mass represent a major goal in the care of cancer
      patients. However, early diagnosis of cancer cachexia is currently limited for
      several reasons. Indeed, cachexia development is variable according to tumor and
      host characteristics. In addition, safe, accessible and non-invasive tools to
      detect skeletal muscle atrophy are desperately lacking in clinical practice.
      Finally, the precise molecular mechanisms and the key players involved in cancer
      cachexia remain poorly characterized. The need for an early diagnosis of cancer
      cachexia supports therefore the quest for a biomarker that might reflect skeletal
      muscle atrophy process. Current research offers different promising ways to
      identify such a biomarker. Initially, the quest for a biomarker of cancer
      cachexia has mostly focused on mediators of muscle atrophy, produced by both
      tumor and host, in an attempt to define new therapeutic approaches. In another
      hand, molecules released by the muscle into the circulation during the atrophy
      process have been also considered as potential biomarkers. More recently, several
      "omics" studies are emerging to identify new muscular or circulating markers of
      cancer cachexia. Some genetic markers could also contribute to identify patients
      more susceptible to develop cachexia. This article reviews our current knowledge
      regarding potential biomarkers of cancer cachexia.

PMID- 28739223
TI  - Decreased mortality in patients prescribed vancomycin after implementation of
      antimicrobial stewardship program.
AB  - BACKGROUND: The impact of an antimicrobial stewardship program (ASP) on 30-day
      mortality rates was evaluated in patients prescribed vancomycin in a Veterans
      Affairs hospital. METHODS: A retrospective chart review of patients receiving a
      minimum of 48 hours of vancomycin during October 2006-July 2014. A multivariate
      logistic regression analysis was used to determine predictors of mortality.
      Interventions of the ASP consist of appropriate antibiotic selection, dosing,
      microbiology, and treatment duration. RESULTS: Death occurred in 12.4% of 453
      patients. Of the 56 deaths, 64.3% occurred during prestewardship versus 35.7%
      during stewardship (P = .021). Increased mortality was associated with pre-ASP
      (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.13-4.27), age (unit OR,
      1.08; 95% CI, 1.05-1.12), nephrotoxicity (OR, 3.24; 95% CI, 1.27-8.01), and
      hypotension (OR, 3.28; 95% CI, 1.42-7.44). Patients treated in the intensive care
      unit were associated with increased mortality. Patients in the stewardship group
      experienced lower rates of mortality, which may be caused by interventions
      initiated by the stewardship team, including minimizing nephrotoxicity and
      individualized chart review. CONCLUSIONS: Mortality in patients treated with
      vancomycin was decreased after antimicrobial stewardship was implemented. As
      anticipated, older age, hypotension, nephrotoxicity, and intensive care unit
      admission were associated with an increased incidence of mortality.

PMID- 28739224
TI  - ESBL-producing Escherichia coli and Klebsiella pneumoniae: The most prevalent
      clinical isolates obtained between 2005 and 2012 in Mexico.
AB  - OBJECTIVES: To identify the prevalence of ESBL genes in the principal group of
      Enterobacteriaceae causing nosocomial infections and to identify the phylogenetic
      group in Escherichia coli isolates. METHODS: There were collected 1084 ESBL
      producing Enterobacteriaceae isolates during 2005-2012 from adult patients from
      14 hospitals and corresponding to eight states and five regions (SE, S, N, W and
      NW) in Mexico. The CTX-M-(CTX-M-1 group), SHV-, TLA- and GES-type ESBLs genes
      were screened. The respective alleles were determined in the most of ESBLs genes.
      In E. coli isolates selected were used to identify the phylogenetic group.
      RESULTS: The ESBL-producing Escherichia coli and Klebsiella pneumoniae
      corresponded the most prevalent clinical isolates. CTX-M-type ESBLs genes were
      the most common, followed by SHV-type, GES-type and the ESBLs TLA-1 gene. The
      allelic frequency showed to CTX-M-15 ESBL the most prevalent, followed by the SHV
      12, SHV-5 and GES-1, GES-19 in the GES family. Among ESBL-producing E. coli
      isolates the phylogenetic groups A and D were the most common ones. CONCLUSIONS:
      The present study showed an epidemiological change in terms of bacterial species,
      placing E. coli as the most frequently isolated bacteria among ESBL-producing
      Enterobacteriaceae in Mexico, followed by K. pneumoniae. This frequency is
      accompanied by a high frequency of ESBL CTX-M-15.

PMID- 28739225
TI  - Distribution scheme of antituberculosis drug resistance among HIV patients in a
      referral centre over 10 years.
AB  - OBJECTIVES: Antituberculosis drug resistance is increasing among tuberculosis
      (TB) patients globally, particularly in those who are human immunodeficiency
      virus (HIV)-positive. The aim of this study was to determine the pattern of anti
      TB drug resistance in these patients in an effort to improve successful treatment
      outcomes with a proper regimen. METHODS: A cross-sectional study was conducted on
      adult TB/HIV co-infected patients from 2005-2015. The pattern of anti-TB drug
      resistance was evaluated among HIV-positive patients with and without a history
      of TB treatment. Categorisation was made as follows: isoniazid (INH)-resistant;
      rifampicin (RIF)-resistant; or multidrug-resistant (MDR). RESULTS: A total of 52
      patients were enrolled in this study (median age 38 years). Among the 52
      patients, 18 (34.6%) were MDR-TB patients and the rest were monoresistant TB
      (resistant either to INH or RIF). INH resistance was the most common resistance
      pattern (36.5%) noted among patients and was significantly associated with new TB
      cases (69% vs. 31%; P=0.01). During TB treatment, 3/48 patients (6.3%) failed
      treatment and 11/48 (22.9%) died. Patients with MDR-TB were more likely to die
      during treatment (44.4% vs. 10%; P=0.011). CONCLUSIONS: Any drug resistance in
      previously treated TB cases among HIV-infected patients remains high. The risk of
      death is increasing in MDR-TB/HIV co-infected patients.

PMID- 28739226
TI  - Draft genome sequence of a multidrug-resistant Aeromonas hydrophila ST508 strain
      carrying rmtD and blaCTX-M-131 isolated from a bloodstream infection.
AB  - Here we report the draft genome sequence of a multidrug-resistant (MDR) Aeromonas
      hydrophila strain belonging to sequence type 508 (ST508) isolated from a human
      bloodstream infection. Assembly and annotation of this draft genome resulted in
      5028498bp and revealed the presence of 16S rRNA methylase rmtD and blaCTX-M-131
      genes encoding high-level resistance to aminoglycosides and cephalosporins,
      respectively, as well as multiple virulence genes. This draft genome can provide
      significant information for understanding mechanisms on the establishment and
      treatment of infections caused by this pathogen.

PMID- 28739227
TI  - Gentamicin susceptibility of 567 clinical group B streptococcal isolates.

PMID- 28739228
TI  - Listeria monocytogenes in raw milk, milking equipment and dairy workers:
      Molecular characterization and antimicrobial resistance patterns.
AB  - OBJECTIVES: The aim of this study was to evaluate the genetic relatedness and
      patterns of antimicrobial resistance amongst L. monocytogenes isolated from raw
      milk, milking equipment, and hand swabs from workers in dairy farms. METHODS: A
      total of 300 samples of raw milk, milking equipment, and hand swabs were
      collected from four dairy farms to examine the presence of Listeria species.
      Suspected isolates were further identified by VITEK-2 system and Polymerase Chain
      Reaction (PCR). Antimicrobial susceptibility of the L. monocytogenes isolates was
      determined, and genotyping analysis was performed by enterobacterial repetitive
      intergenic consensus-polymerase chain reaction (ERIC-PCR). RESULTS: Listeria spp.
      was isolated from 79 (26.3%) of the 300 samples, including 29 (36.7%), 32
      (40.5%), and 18 (22.8%) isolates found in raw milk, milking equipment, and hand
      swabs, respectively. L. monocytogenes was the most common isolated (87.3%)
      species, while the remaining Listeria isolates were L. innocua (12.7%). Among the
      69 L. monocytogenes isolates, 42 (60.8%) showed the mutual presence of hlyA,
      prfA, inlA, and inlB virulence-associated genes. L. monocytogenes isolates from
      raw milk, milking equipment, and hand swabs showed high genetic relatedness. The
      potentially virulent L. monocytogenes isolates were most frequently resistance to
      tetracycline and clindamycin (81%, each) followed by rifampicin (71.4%), whereas,
      antimicrobial susceptibility was most frequently observed for ampicillin,
      levofloxacin, moxifloxacin, linezolid, and tigecycline (100%, each). Furthermore,
      88% of L. monocytogenes isolates showed multidrug-resistance. CONCLUSIONS: The
      findings of this study show that the contamination of dairy farms with L.
      monocytogenes is relatively high, and highlight the emergence of multi-drug
      resistant L. monocytogenes in dairy farms. However, ampicillin is a good choice
      for treatment of listeriosis in the study area.

PMID- 28739230
TI  - An 11-Year-Old Who Suffered Multiple Traumatic Injuries Secondary to a House
      Explosion.

PMID- 28739231
TI  - Management of Traumatic Intracranial Hypertension: Old Questions With New
      Answers.

PMID- 28739232
TI  - Conflict of Interest.

PMID- 28739234
TI  - Lidia With an "I" Not a "Y".

PMID- 28739236
TI  - Good Grief!

PMID- 28739237
TI  - Certification in Transport Nursing: Adding Power to the Privilege.

PMID- 28739238
TI  - Characteristics of Fixed Wing Air Ambulance Transports in Victoria, Australia.
AB  - OBJECTIVE: Air medical transport is important for the transfer of patients in the
      prehospital and interhospital environment. Few studies have described the
      services provided by fixed wing ambulances or the broader clinical profiles of
      patients they transport. Such information may be useful for the planning and
      allocation of resources, assistance with training, and refining clinical
      protocols. We sought to describe the characteristics of patients transported by
      fixed wing aircraft at Air Ambulance Victoria (AAV) and the service AAV provides
      in Victoria, Australia. METHODS: A retrospective data review of patients
      transported by AAV fixed wing aircraft between January 1, 2011, and June 30,
      2015, was performed. Data were sourced from the Ambulance Victoria data
      warehouse. Retrievals involving physicians were excluded. RESULTS: A total of
      16,579 patients were transported during the study period, with a median age of 66
      years. Most patients were male (58.7%), and cardiovascular/hematologic conditions
      (27.2%) were most common. Overall, 51.7% of cases were prebooked routine
      transfers, 47.4% were interhospital routine transfers, and 0.9% were primary
      responses. Caseloads were largest in the regions furthest from the capital city.
      CONCLUSION: The AAV fixed wing service in Victoria enables regional and remote
      patients to be transported to definitive care without major disruption to ground
      ambulances.

PMID- 28739239
TI  - Acute Coronary Syndrome Evacuated by a Helicopter From the Scene.
AB  - OBJECTIVE: The purpose of this study was to investigate the safety of evacuating
      patients using a physician-staffed helicopter (Dr. Heli). METHODS: We
      retrospectively investigated all of the patients with acute coronary syndrome
      (ACS) who were transported by a Dr. Heli between April 2004 and March 2016. The
      scene group included subjects evacuated from the scene by the Dr. Heli. The
      interhospital group included subjects transported to a nearby medical facility by
      a ground ambulance and then transported to our hospital by a Dr. Heli. RESULTS:
      The scene and interhospital groups included 170 subjects and 592 subjects,
      respectively. There were no significant differences between the 2 groups with
      regard to sex and survival ratios. However, the patients in the scene group were
      significantly younger than those in the interhospital group. The ratio of
      prehospital cardiopulmonary arrest in the scene group was significantly higher
      than in the interhospital group. After excluding subjects who were over 80 years
      of age, there were no significant differences between the 2 groups with regard to
      age. However, the same tendencies remained. CONCLUSION: This result indirectly
      suggests the safety of using the Dr. Heli to evacuate ACS patients from the
      scene.

PMID- 28739240
TI  - Evaluation of Situation, Background, Assessment, Recommendation Tool During
      Neonatal and Pediatric Interfacility Transport.
AB  - OBJECTIVE: We aimed to determine if the implementation of Situation, Background,
      Assessment, Recommendation (SBAR) training improved the quality of real-life
      telephone communication. We evaluated interfacility neonatal and pediatric
      transports performed by registered nurses, respiratory therapists, and physicians
      (MDs). METHODS: This was a quality improvement study performed to evaluate
      telephone communication before and after SBAR training. Training consisted of
      lectures, review of audio files, and simulated role-playing. Recorded audio files
      of real-life transports were evaluated for clarity and content by 3 raters using
      a standardized scoring tool. RESULTS: Ninety-four and ninety-three calls were
      evaluated before and after the intervention, respectively. The total item scores
      were higher posttraining (mean +/- standard deviation [pre: 15.06 +/- 2.60, post:
      17.60 +/- 2.61], P < .001). Global rating scores >= 4 were higher in the
      posttraining group (pre: 50.0% vs. post: 66.7%; P = .02; odds ratio = 1.43; 95%
      confidence interval, 1.04-1.97). There was no significant difference in the
      duration of calls (mean +/- SD [pre: 9.29 +/- 4.59 minutes, post: 9.70 +/- 4.65
      minutes). In subgroup analysis, the total item score was significantly improved
      posttraining for registered nurses and respiratory therapists but not MDs.
      CONCLUSION: Standardized SBAR training was effective in improving telephone
      communication by RNs and RTs. The inclusion of SBAR training routinely within the
      educational curriculum of transport programs can enhance communication.

PMID- 28739241
TI  - Hospital Mortality Based on the Mode of Emergency Medical Services
      Transportation.
AB  - OBJECTIVE: We assessed the presentations and outcomes of trauma patients
      transported by helicopter emergency medical services (HEMS) versus ground
      emergency medical services (GEMS). METHODS: A retrospective analysis of trauma
      registry data at a level I trauma center was conducted for patients transported
      by GEMS and HEMS between 2011 and 2013. Data were analyzed and categorized based
      on the mode of transportation. RESULTS: A total of 4,596 trauma patients were
      admitted to the hospital with a mean age of 31 +/- 15 years. Injured patients
      were transported to the trauma center by GEMS (93.3%) and HEMS (6.7%). The common
      mechanisms of injury were motor vehicle crash (37%) and falls (25%). Compared
      with GEMS, patients transported by HEMS were characterized by having a greater
      injury severity, more proportion of traumatic brain injury, on-scene intubation,
      and a 2.5-fold higher mortality. However, the impact of mode of transportation on
      the hospital mortality among severely injured patients has disappeared after
      adjusting for potential confounders. CONCLUSION: Patients transported by HEMS may
      have different characteristic features and outcomes when compared with GEMS.
      However, further work is needed to identify the subgroups of trauma patients who
      clearly benefit from the use of HEMS.

PMID- 28739242
TI  - Helicopter Emergency Medical Service Simulation Training in the Extreme:
      Simulation-based Training in a Mountain Weather Chamber.
AB  - Mountain rescue operations often confront crews with extreme weather conditions.
      Extremely cold temperatures make standard treatment sometimes difficult or even
      impossible. It is well-known that most manual tasks, including those involved in
      mountain rescue operations, are slowed by extremely cold weather. To lessen and
      improve the decrement in performance of emergency medical treatment caused by
      cold-induced manual impairment and inadequate medical equipment and supplies,
      simulation training in a weather chamber, which can produce wind and temperatures
      up to -22 degrees C, was developed. It provides a promising tool to train the
      management of complex multidisciplinary settings, thus reducing the occurrence of
      fatal human and technical errors and increasing the safety for both the patient
      and the mountain emergency medical service crew.

PMID- 28739243
TI  - HEAVEN Criteria: Derivation of a New Difficult Airway Prediction Tool.
AB  - OBJECTIVE: Airway management is vitally important in the management of critically
      ill and injured patients. Current tools to predict the difficult airway have
      limited application in the emergency airway situation. The aim of this study was
      to derive a novel difficult airway prediction tool for emergency intubation.
      METHODS: A retrospective descriptive analysis was performed in a population of
      air medical rapid sequence intubation patients requiring more than 1 attempt. The
      Delphi technique was used to classify the etiology for airway failure as reported
      by providers as part of a performance improvement database. Etiologies were
      organized into 6 categories, and an acronym was derived for ease of recall.
      RESULTS: A total of 504 patients were screened, with 63 (12%) patients identified
      in whom the initial intubation attempt was unsuccessful. All 63 patients (100%)
      were placed into 1 or more categories (HEAVEN criteria = Hypoxemia, Extremes of
      size, Anatomic challenges, Vomit/blood/fluid, Exsanguination/anemia, and Neck
      mobility issues). The database was relatively modest in size, and many patients
      had more than 1 criterion present, limiting our ability to perform prevalence
      calculations. CONCLUSION: The HEAVEN criteria represent a set of difficult airway
      predictors that may be applied prospectively by emergency airway personnel,
      facilitating airway decision making. These criteria should be validated
      prospectively.

PMID- 28739244
TI  - The 5 T's: Applying Cognitive Science to Improve Prehospital Medical Education.
AB  - Although research on effective teaching methods exists, the application of this
      information in prehospital medical education is limited. Applying lessons from
      the realms of cognitive psychology and neuroscience, prehospital educators can
      enhance their ability to teach. One such concept is the theory of cognitive load.
      Understanding this theory can reduce the mental strain placed on learners and
      allow educators to best accomplish long-term learning success, defined as "far
      transfer" of material to novel contexts. Thus, we propose 5 concise strategies
      gleaned from cognitive science literature: Tell a story, Time, Technical
      elements, Think novelly, and Testing and recall (referred to as the "5 T's").
      Each strategy is grounded in research and applicable to medical education.
      Increased educator awareness and use of these strategies garners the potential to
      transform prehospital medical education.

PMID- 28739245
TI  - Management of Mass Casualties Using Doctor Helicopters and Doctor Cars.
AB  - At approximately 10 o'clock in September 2015, a minibus carrying 18 people
      accidentally slid backwards because of a malfunctioning brake system while
      climbing a steep incline on Togasayama Mountain, colliding with a van (Toyota
      HiAce wagon) carrying 11 people that was situated behind the minibus. Togasayama
      Mountain is located 1 hour by car and 10 minutes by helicopter from our hospital.
      The minibus slid off a roadside cliff at a height of 0.5 m and rolled over after
      colliding with the van. There were 7 victims with yellow tags and 22 with green
      tags. Two Doctor Helicopters and 1 Doctor Car cooperated with the fire
      departments by providing medical treatments, selection of medical facilities, and
      dispersion transportation. In this mass casualty event, there were no
      mortalities, and all of the victims recovered without sequelae. The coordinated
      and combined use of Doctor Helicopters and Doctor Cars in addition to the
      activities of the fire department in response to a mass casualty event resulted
      in appropriate triage, medical treatments, selection of medical facilities, and
      dispersion transportation.

PMID- 28739246
TI  - Three-Dimensional Measurement of Aortic Annulus Dimensions Using Area or
      Circumference for Transcatheter Aortic Valve Replacement Valve Sizing: Does It
      Make a Difference?
AB  - BACKGROUND: The use of transcatheter aortic valve replacement (TAVR) is
      increasing worldwide. We present our 6-year experience using three-dimensional
      (3D) transesophageal echocardiography (TEE) and investigate whether different
      sizing methods of the aortic annulus lead to different prosthesis size that may
      impact outcome. METHODS: We investigated 262 patients who underwent TAVR and had
      3D TEE data sets of the aortic annulus. We have used the area-derived diameter
      (Darea = 2(area/pi)) and the circumference-derived diameter (Dcirc =
      Circumference/pi) to size the prosthesis in separate populations in different
      time periods. RESULTS: The Dcirc method is correlated with lower incidence of
      paravalvular aortic regurgitation (PVAR; odds ratio = 0.44, 95% confidence
      interval, 0.23-0.85; P = .015). Other factors associated with PVAR were the cover
      index, area-mismatch index, and circumference-mismatch index. Retrospectively,
      for the purposes of the study, we used the Edwards-Sapien 3 Valve 3D sizing guide
      in all patients, to predict the hypothetical valve size with each method. In the
      whole population, the calculated Dcirc was higher in all cases (Dcirc = 23.4 +/-
      2.3 mm vs Darea = 22.9 +/- 2.3 mm; P < .001). The two methods had good agreement
      in predicting the valve size (kappa = 0.600). In total, 192 (73.3%) patients were
      assigned for the same prosthesis size, whereas 70 (26.7%) would be eligible for a
      different size, of which 44 (16.7%) would definitely have had a different valve
      implanted. CONCLUSION: Using the aortic annulus area or circumference to
      calculate the annular diameter provides different values. Comparing the two
      methods, a different prosthesis size could have been implanted in 26.7% of
      patients. In our series the use of circumference-derived diameter resulted in
      lower incidence of PVAR. The findings of this study may be independent of the
      imaging modality and may therefore also apply to computed tomography-based aortic
      annulus measurements, but this needs to be further investigated.

PMID- 28739247
TI  - Difficulties with emotion regulation moderate the association between childhood
      history of maltreatment and cortisol reactivity to psychosocial challenge in
      postpartum women.
AB  - Exposure to child maltreatment can lead to long-term emotional difficulties and
      dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. However, no prior
      work has examined emotion regulation as a moderator of the association between
      childhood history of maltreatment and cortisol response to psychosocial
      challenge. Amongst a sample of 140 postpartum women, associations between
      childhood maltreatment, emotion regulation, and cortisol response to a
      computerized Emotional Stroop paradigm were examined using structural equation
      modeling. Three saliva samples (baseline, 20- and 40-min post-challenge) were
      collected and later assayed for cortisol. Stepwise regression analyses revealed
      that difficulties with emotion regulation significantly moderated the association
      between maternal history of child maltreatment and cortisol reactivity (beta=
      0.17, CI.95=-0.31, -0.04, t=-2.51, p=0.01). Specifically, women with higher child
      maltreatment scores and greater difficulties with emotion regulation displayed
      reduced cortisol reactivity. This finding suggests that diminished emotion
      regulation capacity may uniquely contribute to blunted physiological reactivity
      in postpartum women exposed to higher levels of child maltreatment. As the
      postpartum period has significant implications for maternal well-being and infant
      development, these findings are discussed in terms of adaptive responsivity,
      maternal behaviour, and clinical practice.

PMID- 28739248
TI  - The protective effect of hydrogen sulfide (H2S) on traumatic brain injury (TBI)
      induced memory deficits in rats.
AB  - Traumatic brain injury (TBI), as an expanding public health epidemic, is a common
      cause of death among youth. TBI is associated with cognitive deficits and memory
      impairment. Hydrogen sulfide (H2S), a novel gaseous mediator, has been recognized
      as an important neuromodulator and neuroprotective agent in the central nervous
      system. In the present study the potential neuroprotective role of sodium
      hydrosulfide (NaHS), an H2S donor on TBI induced memory deficit in a rat model of
      controlled cortical impact (CCI) injury was investigated. CCI model was used to
      induce TBI. Male rats were randomly assigned into the following groups: control,
      sham, sham treated with NaHS, TBI, and TBI treated with NaHS (3 and 5mg/kg). NaHS
      was injected intraperitoneally 5min before TBI induction. Learning and memory
      were assessed using Morris water maze (MWM) on days 8-12 following injury. CCI
      resulted in MWM deficits. Injured animals showed a slower rate of acquisition
      with respect to the sham-operated animals [F (1, 24)=13.97, P<0.01, two-way
      ANOVA]. NaHS improved spatial memory impairment of injured rats. Treatment with
      NaHS (5 mg/kg) decreased the escape latency [F (1, 24)=7.559, P<0.05, two-way
      ANOVA] and traveled distance [F (1, 12)=6.398, P<0.05, Two way ANOVA)]. In probe
      test, injured animals spent less time in target zone (P<0.05, unpaired t-test)
      and NaHS did not have any effect on this parameter (p>0.05, one way ANOVA). These
      findings suggest that NaHS has a neuroprotective effect on TBI-induced memory
      impairment in rats.

PMID- 28739249
TI  - Intraperitoneal pressure in peritoneal dialysis.
AB  - The measure of intraperitoneal pressure in peritoneal dialysis is easy and
      provides clear therapeutic benefits. However it is measured only rarely in adult
      peritoneal dialysis units. This review aims to disseminate the usefulness of
      measuring intraperitoneal pressure. This measurement is performed in supine
      before initiating the drain of a manual exchange with "Y" system, by raising the
      drain bag and measuring from the mid-axillary line the height of the liquid
      column that rises from the patient. With typical values of 10-16 cmH2O,
      intraperitoneal pressure should never exceed 18 cmH2O. With basal values that
      depend on body mass index, it increases 1-3 cmH2O/L of intraperitoneal volume,
      and varies with posture and physical activity. Its increase causes discomfort,
      sleep and breathing disturbances, and has been linked to the occurrence of leaks,
      hernias, hydrothorax, gastro-esophageal reflux and enteric peritonitis. Less
      known and valued is its ability to decrease the effectiveness of dialysis
      significantly counteracting ultrafiltration and decreasing solute clearance to a
      smaller degree. Because of its easy measurement and potential utility, should be
      monitored in case of ultrafiltration failure to rule out its eventual
      contribution in some patients. Although not yet mentioned in the clinical
      practice guidelines for PD, its clear benefits justify its inclusion among the
      periodic measurements to consider for prescribing and monitoring peritoneal
      dialysis.

PMID- 28739250
TI  - Safety on haemodialysis: Team work paradigm.

PMID- 28739251
TI  - Evidence for an important role of host microRNAs in regulating hepatic fibrosis
      in humans infected with Schistosoma japonicum.
AB  - MicroRNAs (miRNAs) are short, non-coding RNAs that repress the translation of
      target gene transcripts. They have been implicated in various activities such as
      cell proliferation, survival, differentiation, migration and metabolism. We
      report here the first known miRNome and transcriptome analysis of human livers
      displaying advanced fibrosis due to Schistosoma japonicum infection. We present
      evidence that hsa-miR-150-5p, hsa-miR-10a-5p, hsa-miR-199a-3p, hsa-miR-4521, hsa
      miR-222/221, hsa-miR-663b and hsa-miR-143-3p (associated without correction) play
      an important role in hepatic fibrosis by acting on metabolism, organization of
      the extracellular matrix proteins, lipid mobilization and limitation of oxidative
      damage stress.

PMID- 28739252
TI  - Valproic acid inhibits TTX-resistant sodium currents in prefrontal cortex
      pyramidal neurons.
AB  - Valproic acid is frequently prescribed and used to treat epilepsy, bipolar
      disorder and other conditions. However, the mechanism of action of valproic acid
      has not been fully elucidated. The aim of this study was to assess the influence
      of valproic acid (200 MUM) on TTX-resistant sodium currents in mPFC pyramidal
      neurons. Valproic acid inhibited the maximal amplitude and did not change the
      activation parameters of TTX-resistant sodium currents. Moreover, valproic acid
      (2 MUM and 200 MUM) shifted the TTX-resistant sodium channel inactivation curve
      towards hyperpolarisation. In the presence of valproic acid, TTX-resistant sodium
      currents recovered from inactivation more slowly. Valproic acid did not influence
      the use-dependent blockade of TTX-resistant sodium currents. This study suggests
      that a potential new mechanism of the antiepileptic action of valproic acid is,
      among others, inhibition of TTX-resistant sodium currents.

PMID- 28739253
TI  - Key differences between apoC-III regulation and expression in intestine and
      liver.
AB  - ApoC-III is a critical cardiovascular risk factor, and humans expressing null
      mutations in apoC-III are robustly protected from cardiovascular disease. Because
      of its critical role in elevating plasma lipids and CVD risk, hepatic apoC-III
      regulation has been studied at length. Considerably less is known about the
      factors that regulate intestinal apoC-III. In this work, we use primary murine
      enteroids, Caco-2 cells, and dietary studies in wild-type mice to show that
      intestinal apoC-III expression does not change in response to fatty acids,
      glucose, or insulin administration, in contrast to hepatic apoC-III. Intestinal
      apoC-III is not sensitive to changes in FoxO1 expression (which is itself very
      low in the intestine, as is FoxO1 target IGFBP-1), nor is intestinal apoC-III
      responsive to western diet, a significant contrast to hepatic apoC-III
      stimulation during western diet. These data strongly suggest that intestinal apoC
      III is not a FoxO1 target and support the idea that apoC-III is not regulated
      coordinately with hepatic apoC-III, and establishes another key aspect of apoC
      III that is unique in the intestine from the liver.

PMID- 28739254
TI  - Functional analysis of the promoters of the small GTPases RhoA and RhoB in
      embryonic stem cells.
AB  - Small GTPases of the Rho subfamily have been implicated in many physiological and
      pathological processes in various cell types including embryonic stem cells
      (ESCs). In the present study we performed a functional analysis of the promoters
      of the RhoA and the RhoB genes in order to identify regulatory elements that are
      important for their transcriptional control in ESCs. We show that RhoA mRNA
      levels were significantly higher compared with the RhoB mRNA levels in ESCs as
      well in various cancer cell lines and this difference could be accounted for by
      differences in the activities of the corresponding promoters. Deletion analysis
      of the RhoA and RhoB promoters in ESCs revealed that the proximal regions contain
      regulatory elements that are critical for their activity. Both proximal promoters
      contain CCAAT boxes and mutagenesis of these elements decreased significantly the
      activity of both promoters suggesting a coordinated regulation of the two genes
      by CCAAT box binding factors. Finally, we show that both genes are subjects to
      autoregulation in ESCs and in the case of RhoB, this autoregulation requires the
      GTPase activity of the Rho proteins. Understanding the mechanisms that control
      the transcription of Rho GTPases in ESCs may shed new light into the still
      unknown roles of these proteins in stem cell functions.

PMID- 28739255
TI  - WP1066, a small molecule inhibitor of the JAK/STAT3 pathway, inhibits ceramide
      glucosyltransferase activity.
AB  - WP1066 is a well-known inhibitor of the JAK/STAT3 signaling pathway. By a screen
      of known small molecule inhibitors of various enzymes and protein factors, we
      identified WP1066 as a ceramide glucosyltransferase inhibitor. Ceramide
      glucosyltransferase catalyzes the first glycosylation step during
      glycosphingolipid synthesis. We found that WP1066 inhibited the activity of
      ceramide glucosyltransferase with an IC50 of 7.2 MUM, and that its action was
      independent of JAK/STAT3 pathway blockade. Moreover, the modes of inhibition of
      ceramide glucosyltransferase were uncompetitive with respect to both C6-NBD
      cermide and UDP-glucose.

PMID- 28739256
TI  - Palmitoylation of Ca2+ channel subunit CaVbeta2a induces pancreatic beta-cell
      toxicity via Ca2+ overload.
AB  - High blood glucose triggers the release of insulin from pancreatic beta cells,
      but if chronic, causes cellular stress, partly due to impaired Ca2+ homeostasis.
      Ca2+ influx is controlled by voltage-gated calcium channels (CaV) and high
      density of CaV in the plasma membrane could lead to Ca2+ overload. Trafficking of
      the pore-forming CaValpha1 subunit to the plasma membrane is regulated by
      auxiliary subunits, such as the CaVbeta2a subunit. This study investigates, using
      Ca2+ imaging and immunohistochemistry, the role of palmitoylation of CaVbeta2a in
      maintaining Ca2+ homeostasis and beta cell function. RNA sequencing data showed
      that gene expression of human CACNB2, in particular CACNB2A (CaVbeta2a), is
      highest in islets when compared to other tissues. Since CaVbeta2a can be
      regulated through palmitoylation of its two cysteines, CaVbeta2a and its mutant
      form were overexpressed in pancreatic beta cells. Palmitoylated CaVbeta2a
      tethered to the plasma membrane and colocalized with CaV1.2 while the mutant form
      remained in the cytosol. Interestingly, CaVbeta2a overexpression raised basal
      intracellular Ca2+ and increased beta cell apoptosis. Our study shows that
      palmitoylation of CaVbeta2a is necessary for CaValpha1 trafficking to the plasma
      membrane. However, excessive number of palmitoylated CaVbeta2a leads to Ca2+
      overload and beta cell death.

PMID- 28739257
TI  - Lack of epithelial PPARgamma causes cystic adenomatoid malformations in mouse
      fetal lung.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) plays an important
      role in lipid and glucose metabolism. In this study, the function of PPARgamma on
      lung development was investigated. Lung-specific Pparg conditional knockout mice
      (PpargDeltaLuEpC) were developed using Cre-Lox system. PpargDeltaLuEpC mice
      showed abnormal lung development with enlarged airspaces and followed by increase
      of apoptotic cells at E14.5 to E18.5. Gene analysis revealed that expression of
      Pmaip1, a gene related to apoptosis, was significantly increased while expression
      of Retnla, a gene related to anti-apoptosis, was dramatically decreased in the
      fetal lung (E14.5) of PpargDeltaLuEpC mice. In addition, expression of Pthlh, a
      gene phenotypically expressed in the congenital cystic adenomatoid malformation
      (CCAM), was increased at E14.5 to E18.5 in the lung of PpargDeltaLuEpC mice. Cell
      culture studies revealed that PPARgamma could bind to promoter region of Pthlh
      gene as a repressor in the immortalized mouse lung epithelial cell line MLE-15.
      Surprisingly, phenotypic changes in MLE-15-shPparg cells, stably transfected with
      shPparg plasmid, were similar to the PpargDeltaLuEpC mice model. In addition, MLE
      15-shPparg cells were easily detached from the cultured plate when cold phosphate
      buffered saline was applied. Furthermore, expression of Cdh1, a gene related to
      cell adhesion, was significantly reduced in the MLE-15-shPparg cells. Taken
      together, PPARgamma may play an important role in fetal lung development via
      alveolar cell-to-cell adhesion system.

PMID- 28739258
TI  - Inhibition by divalent metal ions of human histidine triad nucleotide binding
      protein1 (hHint1), a regulator of opioid analgesia and neuropathic pain.
AB  - Human histidine triad nucleotide binding protein 1 (hHint1) is a purine
      nucleoside phosphoramidase and adenylate hydrolase that has emerged as a
      potential therapeutic target for the management of pain. However, the molecular
      mechanism of Hint1 in the signaling pathway has remained less clear. The role of
      metal ions in regulating postsynaptic transmission is well known, and the active
      site of hHint1 contains multiple histidines. Here we have investigated the effect
      of divalent metal ions (Cd2+, Cu2+, Mg2+, Mn2+, Ni2+, and Zn2+) on the structural
      integrity and catalytic activity of hHint1. With the exception of Mg2+, all the
      divalent ions inhibited hHint1, the rank of order was found to be Cu2+ >Zn2+
      >Cd2+ >=Ni2+ >Mn2+ based on their IC50 and kin/KI values. A crystal structure of
      hHint1 with bound Cu2+ is described to explain the competitive reversible
      inactivation of hHint1 by divalent cations. All the metal ions exhibited time-
      and concentration- dependent inhibition, with the rate of inactivation highly
      dependent on alterations of the C-terminus. With the exception of Cu2+;
      restoration of inhibition was observed for all the metal ions after treatment
      with EDTA. Our studies reveal a loss in secondary structure and aggregation of
      hHint1 upon incubation with 10-fold excess of copper. Thus, hHint1 appears to be
      structurally sensitive to irreversible inactivation by copper, which may be of
      neurotoxicological and pharmacological significance.

PMID- 28739259
TI  - The Use of Technology by Adolescents With Intellectual and Developmental
      Disabilities.

PMID- 28739260
TI  - Uses and misuses of albumin during resuscitation and in the neonatal intensive
      care unit.
AB  - Albumin is one of the most abundant proteins in plasma and serves many vital
      functions. Neonatal concentrations vary greatly with gestational and postnatal
      age. In critically ill neonates, hypoalbuminemia occurs due to decreased
      synthesis, increased losses or redistribution of albumin into the extravascular
      space, and has been associated with increased morbidities and mortality. For that
      reason, infusion of exogenous albumin as a volume expander has been proposed for
      various clinical settings including hypotension, delivery room resuscitation,
      sepsis and postoperative fluid management. Albumin is often prescribed in infants
      with hypoalbuminemia, hyperbilirubinemia, and protein-losing conditions. However,
      the evidence of these practices has not been reviewed or validated. Albumin
      infusion may initiate highly complex processes that vary according to the
      individual and disease pathophysiology. Indeed, it may be associated with harms
      when misused. In this review, we critically appraise the scientific evidence for
      administering albumin in most conditions encountered in the neonatal intensive
      care unit, while emphasizing the benefits and risks associated with their use.

PMID- 28739262
TI  - Whistling Past the Graveyard.

PMID- 28739261
TI  - The long way to better PCI results in diabetic patients.

PMID- 28739263
TI  - Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older
      Patients with Treatment-Resistant Depression.
AB  - OBJECTIVE: To assess the efficacy and safety of subcutaneous ketamine for
      geriatric treatment-resistant depression. Secondary aims were to examine if
      repeated treatments were safe and more effective in inducing or prolonging
      remission than a single treatment. METHODS: In this double-blind, controlled,
      multiple-crossover study with a 6-month follow-up (randomized controlled trial
      [RCT] phase), 16 participants (>=60 years) with treatment-resistant depression
      who relapsed after remission or did not remit in the RCT were administered an
      open-label phase. Up to five subcutaneous doses of ketamine (0.1, 0.2, 0.3, 0.4,
      and 0.5 mg/kg) were administered in separate sessions (>=1 week apart), with one
      active control (midazolam) randomly inserted (RCT phase). Twelve ketamine
      treatments were given in the open-label phase. Mood, hemodynamic, and
      psychotomimetic outcomes were assessed by blinded raters. Remitters in each phase
      were followed for 6 months. RESULTS: Seven of 14 RCT-phase completers remitted
      with ketamine treatment. Five remitted at doses below 0.5 mg/kg. Doses >= 0.2
      mg/kg were significantly more effective than midazolam. Ketamine was well
      tolerated. Repeated treatments resulted in higher likelihood of remission or
      longer time to relapse. CONCLUSION: Results provide preliminary evidence for the
      efficacy and safety of ketamine in treating elderly depressed. Dose titration is
      recommended for optimizing antidepressant and safety outcomes on an individual
      basis. Subcutaneous injection is a practical method for giving ketamine. Repeated
      treatments may improve remission rates (clinicaltrials.gov; NCT01441505).

PMID- 28739264
TI  - Preface - Matrix metalloproteinases.

PMID- 28739266
TI  - Identification of alpha-helix 4 (alpha4) of Rab11a as a novel Rab11-binding
      domain (RBD): Interaction of Rab11a with the Prostacyclin Receptor.
AB  - The cellular trafficking of numerous G protein-coupled receptors (GPCRs) is known
      to be regulated by Rab proteins that involves a direct protein:protein
      interaction between the receptor and the GTPase. In the case of the human
      prostacyclin receptor (hIP), it undergoes agonist-induced internalization and
      subsequent Rab11a-dependent recyclization involving an interaction between a
      Rab11-binding domain (RBD) localized within its carboxyl-tail domain with Rab11a.
      However, the GPCR-interacting domain on Rab11a itself is unknown. Hence, we
      sought to identify the region within Rab11a that mediates its interaction with
      the RBD of the hIP. The alpha4 helix region of Rab11 was identified as a novel
      binding domain for the hIP, a site entirely distinct from the Switch I/Switch II 
      regions that act as specific binding domain for most other Rab and Ras-like
      GTPase interactants. Specifically, Glu138 within alpha4 helix of Rab11a appears
      to contact with key residues (e.g. Lys304) within the RBD of the hIP, where such
      contacts differ depending on the agonist-activated versus -inactive status of the
      hIP. Through mutational studies, supported by in silico homology modelling of the
      inactive and active hIP:Rab11a complexes, a mechanism is proposed to explain both
      the constitutive and agonist-induced binding of Rab11a to regulate intracellular
      trafficking of the hIP. Collectively, these studies are not only the first to
      identify alpha4 helix of Rab11a as a protein binding domain on the GTPase but
      also reveal novel mechanistic insights into the intracellular trafficking of the
      hIP, and potentially of other members of the GPCR superfamily, involving Rab11
      dependent mechanisms.

PMID- 28739265
TI  - Role of ADAM10 in intestinal crypt homeostasis and tumorigenesis.
AB  - A disintegrin and metalloproteinases (ADAMs) are a family of mSultidomain,
      membrane-anchored proteases that regulate diverse cellular functions, including
      cell adhesion, migration, proteolysis and other cell signaling events.
      Catalytically-active ADAMs act as ectodomain sheddases that proteolytically
      cleave type I and type II transmembrane proteins and some GPI-anchored proteins
      from the cellular surface. ADAMs can also modulate other cellular signaling
      events through a process known as regulated intramembrane proteolysis (RIP).
      Through their proteolytic activity, ADAMs can rapidly modulate key cell signaling
      pathways in response to changes in the extracellular environment (e.g.
      inflammation) and play a central role in coordinating intercellular
      communication. Dysregulation of these processes through aberrant expression, or
      sustained ADAM activity, is linked to chronic inflammation, inflammation
      associated cancer and tumorigenesis. ADAM10 was the first disintegrin
      metalloproteinase demonstrated to have proteolytic activity and is the prototypic
      ADAM associated with RIP activity (e.g. sequential Notch receptor processing).
      ADAM10 is abundantly expressed throughout the gastrointestinal tract and during
      normal intestinal homeostasis ADAM10 regulates many cellular processes associated
      with intestinal development, cell fate specification and maintenance of
      intestinal stem cell/progenitor populations. In addition, several signaling
      pathways that undergo ectodomain shedding by ADAM10 (e.g. Notch, EGFR/ErbB, IL
      6/sIL-6R) help control intestinal injury/regenerative responses and may drive
      intestinal inflammation and colon cancer initiation and progression. Here, I
      review some of the proposed functions of ADAM10 associated with intestinal crypt
      homeostasis and tumorigenesis within the gastrointestinal tract in vivo. This
      article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in
      Pathophysiology edited by Stefan Rose-John.

PMID- 28739267
TI  - H. pylori seroprevalence and risk of diabetes: An ancillary case-control study
      nested in the diabetes prevention program.
AB  - OBJECTIVE: To determine the association between H. pylori infection and risk of
      incident diabetes in adults at high risk for diabetes who participated in the
      Diabetes Prevention Program (DPP) study. METHODS: In a nested case-control study
      conducted among 421 adults with newly diagnosed diabetes and 421 matched
      controls, we examined the association between serological status of H. pylori at
      baseline and risk of incident diabetes over a mean follow-up period of 2.6years.
      Using data from the baseline visit of the DPP, we also examined the cross
      sectional association between presence of H. pylori antibodies and insulin
      sensitivity, insulin secretion and the disposition index-like measure after a 75
      g oral glucose tolerance test (OGTT). RESULTS: At baseline, H. pylori antibodies
      were present in 40% of participants who developed diabetes and 39% of controls.
      After adjusting for matching factors, there was no association between exposure
      to H. pylori and incident diabetes (odds ratio [OR] of 1.04 (95% CI, 0.77 to
      1.40). In cross-sectional analyses, H. pylori status was not significantly
      associated with insulin sensitivity and disposition index-like measure from OGTT.
      CONCLUSIONS: In adults at high risk for diabetes, H. pylori seropositivity was
      not associated with risk of developing diabetes.

PMID- 28739268
TI  - Xpert(r) MTB/RIF: Usefulness for the diagnosis of tuberculosis and resistance to
      rifampicin.
AB  - The advent of the Xpert(r) MTB/RIF technique was a revolution in the diagnosis of
      tuberculosis, especially in areas with high incidence and low resources. It
      allows the detection of Mycobacterium tuberculosis complex and simultaneously the
      most common resistance mutations to rifampicin in less than 2h. For respiratory
      samples the sensitivity is very high, but it decreases for extrapulmonary samples
      and children. Although it is faster and simpler than conventional methods, it
      presents some limitations and new and better techniques are needed to reduce the
      number of cases and deaths caused by tuberculosis. This review aims to assess the
      scientific evidence around the diagnostic performance of Xpert(r) MTB/RIF in
      different types of samples and populations, as well as analyse its strengths and
      limitations for TB diagnosis.

PMID- 28739269
TI  - Extracutaneous atypical syphilis in HIV-infected patients.
AB  - INTRODUCTION AND OBJETIVE: We describe a series of cases of syphilis with
      atypical extracutaneous clinical presentation diagnosed in HIV-infected patients.
      METHODS: Retrospective observational study. All cases of syphilis diagnosed in
      HIV-infected patients during the period between June 2013 and June 2016 in a
      tertiary hospital of the Barcelona metropolitan area were analysed. RESULTS: A
      total of 71 cases of syphilis were diagnosed, 32 of them presenting with clinical
      signs or symptoms. Seven of these cases (9.8% of the total and 21.8% of the
      symptomatic cases) had atypical presentations with extracutaneous involvement:
      ocular (4), gastric (1), multiple hepatic abscesses (1) and generalised
      adenopathies (1). Patients were treated with intramuscular or intravenous
      penicillin and the clinical and serological evolution was good in all of them.
      CONCLUSIONS: Extracutaneous atypical clinical presentations were observed in
      21.8% of symptomatic cases of syphilis in HIV+ patients with ocular involvement
      being the most freqent.

PMID- 28739270
TI  - Discrepancies between the use of MDRD-4 IDMS and CKD-EPI equations, instead of
      the Cockcroft-Gault equation, in the determination of the dosage of direct oral
      anticoagulants in patients with non-valvular atrial fibrillation.
AB  - BACKGROUND AND OBJECTIVE: Direct oral anticoagulants (DOACs) require dose
      adjustment according to estimated clearance creatinine (eClCr) using the
      Cockcroft-Gault (CG) equation. There are discrepancies with the equations that
      estimate glomerular filtration rate (eGFR). We analyse how the use of the CKD-EPI
      and MDRD-4 IDMS equations affect the recommended dosage for ACODs. PATIENTS AND
      METHODS: Retrospective study of patients with non-valvular atrial fibrillation
      seen at a cardiology clinic between November 2012 and August 2014. Patients were
      reclassified according to the recommended dosage for dabigatran, rivaroxaban,
      apixaban and edoxaban, based on the eGFR equation used. Other clinical factors
      are taken into account, according to the product label. We analysed the
      percentage of discordance. RESULTS: Four hundred and fifty-four patients, 53.3%
      men, with a mean age of 68.7+/-13.8 years were studied. The mean intra-individual
      differences recorded for the CG equation were 3.9ml/min/1.73m2 with MDRD-4 IDMS
      (95% CI 1.4-6.4, P=.003) and 11.3ml/min/1.73m2 with CKD-EPI (95% CI 8.9-13.7,
      P<.001). A gradient is observed in the discordance of the posology (apixaban
      1.1%, dabigatran 3.5%, edoxaban 5.7%, rivaroxaban 8.4% with MDRD-4 IDMS).
      Differences were limited to patients with eClCr<60ml/min and were more evident
      in>=75 years in which the eGFR equations overestimate renal function.
      CONCLUSIONS: In patients with non-valvular atrial fibrillation, especially with
      renal failure and in the elderly, eGFR equations tend to overestimate renal
      function relative to CG and therefore suggest an overdose of DOACs.

PMID- 28739271
TI  - Purification of dirucotide, a synthetic 17-aminoacid peptide, by ion exchange
      centrifugal partition chromatography.
AB  - Dirucotide is a synthetic drug candidate for the treatment of multiple sclerosis.
      This 17-aminoacid peptide was successfully purified by ion exchange centrifugal
      partition chromatography. The optimized conditions involved the biphasic methyl
      tert-butyl ether/acetonitrile/n-butanol/water (2:1:2:5, v/v) solvent system in
      the descending mode, the di(2-ethylhexyl)phosphoric acid cation-exchanger with an
      exchanger (di(2-ethylhexyl)phosphoric acid)/dirucotide mole ratio of 100 and Ca2+
      ions in aqueous solution as displacer. Critical impurities were efficiently
      eliminated and dirucotide was recovered in high yield and purity (69% and 98%,
      respectively) and with a productivity of 2.29g per liter of stationary phase per
      hour.

PMID- 28739272
TI  - An on-line analytical approach for detecting haptens in Shuang-huang-lian powder
      injection.
AB  - Shuang-huang-lian powder injection (SHLPI) is a traditional Chinese medicine
      injection (TCMI) frequently used in the clinical treatment of faucitis,
      bronchitis, and other viral and bacterial infections of upper respiratory tract.
      However, its allergenic reactions, being the main adverse effects (AEs) of SHLPI,
      have been a serious problem of its clinical safety. This problem has not been
      solved due to short of methods for detecting haptens in complex TCMIs. In this
      study, an on-line high-performance liquid chromatography-diode-array detector
      mass spectrometry combined with bovine serum albumin-fluorescence detector (HPLC
      DAD-MS-BSA-FLD) system was established for the first time, validated and applied
      for identification of haptens in SHLPI. Fourteen of 35 identified compounds
      showed BSA binding activity, and they were six flavonoids, six caffeoylquinic
      acids (CQAs), and two phenylethanoid glycosides. The structure-activity
      relationships of 10 active components were studied, and their ability of
      sensitization together with that of two CQAs were further verified by ELISA
      assay. It was found that 10 compounds had sensitization, and flavonoids showed
      stronger sensitizability than CQAs while the diCQAs were slightly stronger than
      caffeoylquinic acids. The system was validated using 3-CQA as a positive control,
      and was proved to have good reproducibility, stability, precision (RSD<0.1%) and
      linearity (R2>0.9993). This online system is fast, sensitive and efficient for
      screening haptens in traditional Chinese medicine injection (TCMI), provides a
      new approach to reveal the chemical basis of haptens in TCMIs.

PMID- 28739273
TI  - Analysis of packing microstructure and wall effects in a narrow-bore ultrahigh
      pressure liquid chromatography column using focused ion-beam scanning electron
      microscopy.
AB  - Column wall effects are well recognized as major limiting factor in achieving
      high separation efficiency in HPLC. This is especially important for modern
      analytical columns packed with small particles, where wall effects dominate the
      band broadening. Detailed knowledge about the packing microstructure of packed
      analytical columns has so far not been acquired. Here, we present the first three
      dimensional reconstruction protocol for these columns utilizing focused ion-beam
      scanning electron microscopy (FIB-SEM) on a commercial 2.1mm inner diameter*50mm
      length narrow-bore analytical column packed with 1.7MUm bridged-ethyl hybrid
      silica particles. Two sections from the packed bed are chosen for reconstruction
      by FIB-SEM: one from the bulk packing region of the column and one from its
      critical wall region. This allows quantification of structural differences
      between the wall region and the center of the bed due to effects induced by the
      hard, confining column wall. Consequences of these effects on local flow velocity
      in the column are analyzed with flow simulations utilizing the lattice-Boltzmann
      method. The reconstructions of the bed structures reveal significant structural
      differences in the wall region (extending radially over approximately 62 particle
      diameters) compared to the center of the column. It includes the local reduction
      of the external porosity by up to 10% and an increase of the mean particle
      diameter by up to 3%, resulting in a decrease of the local flow velocity by up to
      23%. In addition, four (more ordered) layers of particles in the direct vicinity
      of the column wall induce local velocity fluctuations by up to a factor of three
      regarding the involved velocity amplitudes. These observations highlight the
      impact of radial variations in packing microstructure on band migration and
      column performance. This knowledge on morphological peculiarities of column wall
      effects helps guiding us towards further optimization of the packing process for
      analytical HPLC columns.

PMID- 28739274
TI  - Extended effective carbon number concept in the quantitative analysis of multi
      ethers using predicted response factors.
AB  - Flame ionized detector has been such widely applied in chemical analysis since
      its great invention and the discovery of chem-ionization. Thanks to the excellent
      contribution of Sternberg and the successors in this field, effective carbon
      number concept (ECN) can make the analysis calibration greatly simplified
      especially when authentic standard substances are unavailable or in the
      complicated case such as petrochemical industry and biomass processing. To
      supplement the ECN rule in multi-ethers, this work determined relative response
      factors of poly(oxymethylene) dimethyl ethers experimentally, and developed a
      probabilistic P1-P2 effective carbon number model (P-ECN) for multi-ethers
      compounds. showed this method could improve the precision of quantitative
      analysis for poly(oxymethylene) dimethyl ethers and could predict relative
      response factors of other ethers with similar structure to a degree. LOD for each
      DMMn monomer ranged between 0.4-0.7 ng, and MDL ranged between 2 and 4 ug/mL. In
      the practical quantitation of diluted samples at level of 10 ug/mL, the relative
      standard deviation was less than 5%. Practical ethers-fuel blend with complex
      composition also was quantified with errors less than 3%.

PMID- 28739275
TI  - Evaluation of solvent systems for optimized extractables studies of single use
      bioprocessing solutions.
AB  - Despite their advantages, there is concern that single-use systems used in
      biopharmaceutical manufacture might release potentially toxic substances during
      standard unit operations that negatively impact cell growth. Characterization of
      the extractables profile for single-use systems is necessary to know which
      compounds potentially become leachables under operational cell culture
      conditions. A key issue in the design of extractables studies is the composition
      of the model solvent, in particular its pH and polarity. In this study, a new
      approach, based on design of experiments (DoE), has been applied to determine the
      composition of the model solvent for extractable profiling of single-use bags
      (SUBs). Particular focus was placed on the determination of the degradation
      products of the antioxidant Irgafos 168(r), due to evidence that some of these
      degradation products have cytotoxic effects on CHO cells. Results indicated that
      2-propanol:water is the most appropriate solvent for the extraction of highly
      hydrophobic compounds with polar groups and/or acid-base properties from SUBs.
      The described DoE approach simplifies the number of experiments, evaluates all
      possible solvent water mixtures to select the best extraction solvent based on
      polarity, establishes the influence of each variable and provides information
      about variable interaction, which represents an important improvement over
      current best practice. The developed approach was applied to seven SUBs from
      different vendors and production dates facilitating the identification of
      potentially non-satisfactory films for cultivation of CHO cell lines under
      process conditions.

PMID- 28739277
TI  - Selection and implementation of emotion regulation strategies in major depressive
      disorder: An integrative review.
AB  - Emotion regulation (ER), broadly defined, has been implicated in mental health,
      including major depressive disorder (MDD). We review empirical studies examining
      selection and implementation of ER strategies in adults with current or past MDD.
      We focus on eight strategies (rumination, distraction, cognitive reappraisal,
      suppression, acceptance, savoring, positive rumination, dampening), organizing
      the review by research design: (1) self-reported habitual use (i.e., trait) of ER
      strategies, (2) spontaneous use of ER strategies in laboratory settings, (3)
      experimentally instructed ER strategies, and (4) use of ER strategies in
      naturalistic settings. Reviewed findings suggest that MDD is associated with
      unskillful selection of ER strategies-indexed by self-reported habitual use of ER
      strategies-but not impaired abilities to implement them; in fact, those with
      current MDD and MDD in remission show intact abilities to implement many ER
      strategies when instructed to do so. Additionally, the vast majority of research
      examines trait ER, while there is a dearth of laboratory and naturalistic studies
      using MDD samples. There are also discrepant findings on habitual use of ER
      strategies assessed by self-reports and spontaneous use of ER strategies in the
      lab. We discuss implications of reviewed findings and five areas for future
      research in emotion dysregulation in MDD.

PMID- 28739276
TI  - A Process of Resection-Dependent Nonhomologous End Joining Involving the Goddess
      Artemis.
AB  - DNA double-strand breaks (DSBs) are a hazardous form of damage that can
      potentially cause cell death or genomic rearrangements. In mammalian G1- and G2
      phase cells, DSBs are repaired with two-component kinetics. In both phases, a
      fast process uses canonical nonhomologous end joining (c-NHEJ) to repair the
      majority of DSBs. In G2, slow repair occurs by homologous recombination. The slow
      repair process in G1 also involves c-NHEJ proteins but additionally requires the
      nuclease Artemis and DNA end resection. Here, we consider the nature of slow DSB
      repair in G1 and evaluate factors determining whether DSBs are repaired with fast
      or slow kinetics. We consider limitations in our current knowledge and present a
      speculative model for Artemis-dependent c-NHEJ and the environment underlying its
      usage.

PMID- 28739278
TI  - p38MAPK plays a critical role in induction of a pro-inflammatory phenotype of
      retinal Muller cells following Zika virus infection.
AB  - Zika virus (ZIKV) infection has been associated with ocular abnormalities such as
      chorioretinal atrophy, optic nerve abnormalities, posterior uveitis and
      idiopathic maculopathy. Yet our knowledge about ZIKV infection in retinal cells
      and its potential contribution to retinal pathology is still very limited. Here
      we found that primary Muller cells, the principal glial cells in the retina,
      expressed a high level of ZIKV entry cofactor AXL gene and were highly permissive
      to ZIKV infection. In addition, ZIKV-infected Muller cells exhibited a pro
      inflammatory phenotype and produced many inflammatory and growth factors. While a
      number of inflammatory signaling pathways such as ERK, p38MAPK, NF-kappaB,
      JAK/STAT3 and endoplasmic reticulum stress were activated after ZIKV infection,
      inhibition of p38MAPK after ZIKV infection most effectively blocked ZIKV-induced
      inflammatory and growth molecules. In comparison to ZIKV, Dengue virus (DENV),
      another Flavivirus infected Muller cells more efficiently but induced much lower
      pro-inflammatory responses. These data suggest that Muller cells play an
      important role in ZIKV-induced ocular pathology by induction of inflammatory and
      growth factors in which the p38MAPK pathway has a central role. Blocking p38MAPK
      may provide a novel approach to control ZIKV-induced ocular inflammation.

PMID- 28739279
TI  - Eicosapentaenoic acid membrane incorporation impairs cholesterol efflux from
      cholesterol-loaded human macrophages by reducing the cholesteryl ester
      mobilization from lipid droplets.
AB  - A diet containing a high n-3/n-6 polyunsaturated fatty acids (PUFA) ratio has
      cardioprotective properties. PUFAs incorporation into membranes influences the
      function of membrane proteins. We investigated the impact of the membrane
      incorporation of PUFAs, especially eicosapentaenoic acid (EPA) (C20:5 n-3), on
      the anti-atherogenic cholesterol efflux pathways. We used cholesteryl esters (CE)
      loaded human monocyte-derived macrophages (HMDM) to mimic foam cells exposed to
      the FAs for a long period of time to ensure their incorporation into cellular
      membranes. Phospholipid fraction of EPA cells exhibited high levels of EPA and
      its elongation product docosapentaenoic acid (DPA) (C22:5 n-3), which was
      associated with a decreased level of arachidonic acid (AA) (C20:4 n-6). EPA 70MUM
      reduced ABCA1-mediated cholesterol efflux to apolipoprotein (apo) AI by 30%
      without any alteration in ABCA1 expression. The other tested PUFAs, DPA,
      docosahexaenoic acid (DHA) (C22:6 n-3), and AA, were also able to reduce ABCA1
      functionality while the monounsaturated oleic FA slightly decreased efflux and
      the saturated palmitic FA had no impact. Moreover, EPA also reduced cholesterol
      efflux to HDL mediated by the Cla-1 and ABCG1 pathways. EPA incorporation did not
      hinder efflux in free cholesterol-loaded HMDM and did not promote esterification
      of cholesterol. Conversely, EPA reduced the neutral hydrolysis of cytoplasmic CE
      by 24%. The reduced CE hydrolysis was likely attributed to the increase in
      cellular TG contents and/or the decrease in apo E secretion after EPA treatment.
      In conclusion, EPA membrane incorporation reduces cholesterol efflux in human
      foam cells by reducing the cholesteryl ester mobilization from lipid droplets.

PMID- 28739280
TI  - Intramyocellular lipid droplets and insulin sensitivity, the human perspective.
AB  - Skeletal muscle can store excess fat as subcellular lipid droplets (LDs). While
      originally viewed as uninteresting static balls of triacylglycerol, it is now
      clear that myocellular LDs play an active role in myocellular (patho)physiology.
      In this review we aim to discuss the role of LDs in muscle cell insulin
      sensitivity and identify parameters which appear to affect this relationship.
      Moreover, we discuss the application of novel tools permitting detailed
      examination of these parameters. This article is part of a Special Issue
      entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and
      Matthijs Hesselink.

PMID- 28739281
TI  - Ventilation rate in adults with a tracheal tube during cardiopulmonary
      resuscitation: A systematic review.
AB  - AIM: The optimal ventilation rate during cardiopulmonary resuscitation (CPR) with
      a tracheal tube is unknown. We evaluated whether in adults with cardiac arrest
      and a secure airway (tracheal tube), a ventilation rate of 10min-1, compared to
      any other rate during CPR, improves outcomes. METHODS: A systematic review up to
      14 July 2016. We included both adult human and animal studies. A GRADE (Grades of
      Recommendation, Assessment, Development and Evaluation) approach was used to
      evaluate the quality of evidence for each outcome. RESULTS: We identified one
      human observational study with 67 patients and ten animal studies (234 pigs and
      30 dogs). All studies carried a high risk of bias. All studies evaluated for
      return of spontaneous circulation (ROSC). Studies showed no improvement in ROSC
      with a ventilation rate of 10 min-1 compared to any other rate. The evidence for
      longer-term outcomes such as survival to discharge and survival with favourable
      neurological outcome was very limited. CONCLUSION: A ventilation rate
      recommendation of 10 min-1 during adult CPR with a tracheal tube and no pauses
      for chest compression is a very weak recommendation based on very low quality
      evidence.

PMID- 28739283
TI  - The Pharmacology of Gene Therapy.

PMID- 28739282
TI  - Long-term Risk of Pancreatic Malignancy in Patients With Branch Duct Intraductal
      Papillary Mucinous Neoplasm in a Referral Center.
AB  - BACKGROUND & AIMS: Little is known about the development of branch duct
      intraductal papillary mucinous neoplasms (BD-IPMNs). We evaluated long-term
      outcomes of a large cohort of patients with BD-IPMNs to determine risk of
      malignancy and define a subset of low-risk BD-IPMNs. METHODS: We performed a
      retrospective analysis of data from 577 patients with suspected or presumed BD
      IPMN under surveillance at the Massachusetts General Hospital. Patients underwent
      cross-sectional imaging analysis at 3 months or later after their initial
      diagnosis. The diagnosis of BD-IPMN was based on the presence of unilocular or
      multilocular cysts of the pancreas and a non-dilated main pancreatic duct (<5
      mm). We collected demographic, clinical, and pathology data. Cysts were
      characterized at the time of diagnosis and during the follow-up period. Follow-up
      duration was time between initial cyst diagnosis and date of last visit or death
      for patients without development of pancreatic cancer, date of surgery for
      patients with histologically confirmed malignancy, or date of first discovery of
      malignancy by imaging analysis for patients with unresectable tumors or who
      underwent neoadjuvant treatment before surgery. The primary outcome was risk of
      malignancy, with a focus on patients followed for 5 years or more, compared with
      that of the US population, based on standardized incidence ratio. RESULTS: Of the
      577 patients studied, 479 (83%) were asymptomatic at diagnosis and 363 (63%)
      underwent endoscopic ultrasound at least once. The median follow-up time was 82
      months (range, 6-329 months) for the entire study cohort; 363 patients (63%)
      underwent surveillance for more than 5 years, and 121 (21%) for more than 10
      years. Malignancies (high-grade dysplasia or invasive neoplasm) developed after 5
      years in 20 of 363 patients (5.5%), and invasive cancer developed in 16 of 363
      patients (4.4%). The standardized incidence ratio for patients with BD-IPMNs
      without worrisome features of malignancy at 5 years was 18.8 (95% confidence
      interval, 9.7-32.8; P < .001). One hundred and eight patients had cysts <=1.5 cm
      for more than 5 years of follow-up; only 1 of these patients (0.9%) developed a
      distinct ductal adenocarcinoma. By contrast, among the 255 patients with cysts
      >1.5 cm, 19 (7.5%) developed malignancy (P = .01). CONCLUSIONS: In a
      retrospective analysis of patients with BD-IPMNs under surveillance, their
      overall risk of malignancy, almost 8%, lasted for 10 years or more, supporting
      continued surveillance after 5 years. Cysts that remain <=1.5 cm for more than 5
      years might be considered low-risk for progression to malignancy.

PMID- 28739284
TI  - Role of 5alpha-dihydrotestosterone in testicular development of gilthead seabream
      following finasteride administration.
AB  - In teleosts, spermatogenesis is regulated by pituitary gonadotropins and sex
      steroids. 5alpha-dihydrotestosterone (DHT), derived from testosterone (T) through
      the action of 5alpha-reductase, has recently been suggested to play a
      physiologically important role in some fish species. In this study, gilthead
      seabream, Sparus aurata L., males received an implant of 1MUgT/g body mass (bm)
      or vehicle alone and, 7days later, 1mg finasteride (FIN, an inhibitor of 5alpha
      reductase)/kg bm or vehicle. Serum levels of T, 11-ketotestosterone (11KT), DHT
      and 17beta-estradiol (E2), and the mRNA levels of the main enzymes involved in
      their synthesis, were analysed. T promoted a transient increase in the serum
      levels of T, 11KT and E2 but a decrease in those of DHT at day 15 following T
      injection, in accordance with the up-regulation of mRNA levels of the enzymes
      involved in T transformation to 11KT (coding genes: cyp11b1 and hsd11b) and the
      down-regulation of mRNA levels of the enzyme responsible for T transformation to
      DHT (coding gene: srd5a). Interestingly, a similar effect was observed when FIN
      was injected. However, when fish were injected with T and FIN successively
      (T+FIN), control levels were not recovered at the end of the experimental period
      (28days). DHT seems to regulate E2 serum levels via the down-regulation of mRNA
      levels of aromatase (coding gene: cyp19a1a), which is needed for the
      transformation of T into E2. The testis histology, together with the
      proliferative rates recorded upon T, FIN or T+FIN treatment, suggests that DHT is
      involved in the onset of the meiotic phase of spermatogenesis.

PMID- 28739285
TI  - Promising approaches for the treatment and prevention of viral respiratory
      illnesses.
AB  - Viral respiratory tract infections are the most common human ailments, leading to
      enormous health and economic burden. Hundreds of viral species and subtypes have
      been associated with these conditions, with influenza viruses, respiratory
      syncytial virus, and rhinoviruses being the most frequent and with the highest
      burden. When considering prevention or treatment of viral respiratory tract
      infections, potential targets include the causative pathogens themselves but also
      the immune response, disease transmission, or even just the symptoms. Strategies
      targeting all these aspects are developing concurrently, and several novel and
      promising approaches are emerging. In this perspective we overview the entire
      range of options and highlight some of the most promising approaches, including
      new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of
      natural remedies, and vaccines and public health policies toward prevention. Wide
      scale prevention through immunization appears to be within reach for respiratory
      syncytial virus and promising for influenza virus, whereas additional effort is
      needed in regard to rhinovirus, as well as other respiratory tract viruses.

PMID- 28739286
TI  - Genetic and epigenetic regulation of YKL-40 in childhood.
AB  - BACKGROUND: Circulating levels of the chitinase-like protein YKL-40 are
      influenced by genetic variation in its encoding gene (chitinase 3-like 1
      [CHI3L1]) and are increased in patients with several diseases, including asthma.
      Epigenetic regulation of circulating YKL-40 early in life is unknown. OBJECTIVE:
      We sought to determine (1) whether methylation levels at CHI3L1 CpG sites mediate
      the association of CHI3L1 single nucleotide polymorphisms (SNPs) with YKL-40
      levels in the blood and (2) whether these biomarkers (CHI3L1 SNPs, methylation
      profiles, and YKL-40 levels) are associated with asthma in early childhood.
      METHODS: We used data from up to 2405 participants from the Spanish Infancia y
      Medio Ambiente; the Swedish Barn/Children, Allergy, Milieu, Stockholm,
      Epidemiological survey; and the Dutch Prevention and Incidence of Asthma and Mite
      Allergy birth cohorts. Associations between 68 CHI3L1 SNPs, methylation levels at
      14 CHI3L1 CpG sites in whole-blood DNA, and circulating YKL-40 levels at 4 years
      of age were tested by using correlation analysis, multivariable regression, and
      mediation analysis. Each of these biomarkers was also tested for association with
      asthma at 4 years of age by using multivariable logistic regression. RESULTS: YKL
      40 levels were significantly associated with 7 SNPs and with methylation at 5 CpG
      sites. Consistent associations between these 7 SNPs (particularly rs10399931 and
      rs4950928) and 5 CpG sites were observed. Alleles linked to lower YKL-40 levels
      were associated with higher methylation levels. Participants with high YKL-40
      levels (defined as the highest YKL-40 tertile) had increased odds for asthma
      compared with subjects with low YKL-40 levels (meta-analyzed adjusted odds ratio,
      1.90 [95% CI, 1.08-3.36]). In contrast, neither SNPs nor methylation levels at
      CpG sites in CHI3L1 were associated with asthma. CONCLUSIONS: The effects of
      CHI3L1 genetic variation on circulating YKL-40 levels are partly mediated by
      methylation profiles. In our study YKL-40 levels, but not CHI3L1 SNPs or
      methylation levels, were associated with childhood asthma.

PMID- 28739287
TI  - Effect of home exposure to Staphylococcus aureus on asthma in adolescents.

PMID- 28739288
TI  - Recent advances on extracellular vesicles in therapeutic delivery: Challenges,
      solutions, and opportunities.
AB  - Extracellular vesicles (EVs) are intrinsic mediators of intercellular
      communication in our body, allowing functional transfer of biomolecules (lipids,
      proteins, and nucleic acid) between diverse locations. Such an instrumental role
      evokes a surge of interest within the drug delivery community in tailoring EVs
      for therapeutic delivery. These vesicles represent a novel generation of drug
      delivery systems, providing high delivery efficiency, intrinsic targeting
      properties, and low immunogenicity. In the recent years, considerable research
      efforts have been directed toward developing safe and efficient EV-based delivery
      vehicles. Although EVs are shown to harbor great promise in therapeutic delivery,
      substantial improvements in exploring standardized isolation techniques with high
      efficiency and robust yield, scalable production, standard procedures for EV
      storage, efficient loading methods without damaging EV integrity, understanding
      their in vivo trafficking, and developing novel EV-based nanocarriers are still
      required before their clinical transformation. In this review, we seek to
      summarize the recent advance on harnessing EVs for drug delivery with focus on
      state-of-the-art solutions for overcoming major challenges.

PMID- 28739289
TI  - Higher required dosage of antipsychotics to relieve the symptoms of first-onset
      Acute and Transient Psychotic Disorder (ATPD) predicted the subsequent diagnostic
      transition to schizophrenia: A longitudinal study.

PMID- 28739290
TI  - Implementation of the Canadian CT Head Rule and Its Association With Use of
      Computed Tomography Among Patients With Head Injury.
AB  - STUDY OBJECTIVE: Approximately 1 in 3 computed tomography (CT) scans performed
      for head injury may be avoidable. We evaluate the association of implementation
      of the Canadian CT Head Rule on head CT imaging in community emergency
      departments (EDs). METHODS: We conducted an interrupted time-series analysis of
      encounters from January 2014 to December 2015 in 13 Southern California EDs.
      Adult health plan members with a trauma diagnosis and Glasgow Coma Scale score at
      ED triage were included. A multicomponent intervention included clinical
      leadership endorsement, physician education, and integrated clinical decision
      support. The primary outcome was the proportion of patients receiving a head CT.
      The unit of analysis was ED encounter, and we compared CT use pre- and
      postintervention with generalized estimating equations segmented logistic
      regression, with physician as a clustering variable. Secondary analysis described
      the yield of identified head injuries pre- and postintervention. RESULTS:
      Included were 44,947 encounters (28,751 preintervention and 16,196
      postintervention), resulting in 14,633 (32.6%) head CTs (9,758 preintervention
      and 4,875 postintervention), with an absolute 5.3% (95% confidence interval [CI]
      2.5% to 8.1%) reduction in CT use postintervention. Adjusted pre-post comparison
      showed a trend in decreasing odds of imaging (odds ratio 0.98; 95% CI 0.96 to
      0.99). All but one ED reduced CTs postintervention (0.3% to 8.7%, one ED 0.3%
      increase), but no interaction between the intervention and study site over time
      existed (P=.34). After the intervention, diagnostic yield of CT-identified
      intracranial injuries increased by 2.3% (95% CI 1.5% to 3.1%). CONCLUSION: A
      multicomponent implementation of the Canadian CT Head Rule was associated with a
      modest reduction in CT use and an increased diagnostic yield of head CTs for
      adult trauma encounters in community EDs.

PMID- 28739291
TI  - Pancreatic cancer screening: Still a delusion?
AB  - Pancreatic adenocarcinoma represents the fourth most common cause of cancer
      mortality and death due to pancreatic cancer (PC) have increased since 2003. Its
      incidence has also raised about 30% in the past decade and it is expected to
      become the second cause of cancer mortality by 2020 in the USA. Most PC present
      with metastatic disease and improvements in treatment outcomes for this group
      have been disappointing. These observations support the idea that screening to
      identify patients at an earlier stage might be an important strategy in improving
      overall PC outcomes. Many protocols have been tested, nevertheless, by now there
      is no effective screening program. Given the overall low incidence of disease and
      the current lack of accurate, inexpensive and noninvasive screening tests, the
      consensus is that widespread population-based screening for PC in the general
      population or in patients with only one affected first-degree relative is neither
      practicable nor indicated in most countries. However, a different scenario is
      screening patients with higher risk for PC, most of them with hereditary
      conditions predisposing the development of this neoplasia. In fact, some
      guidelines are now available helping to select these individuals at risk and to
      screen them, in order to achieve early detection of PC.

PMID- 28739292
TI  - A polar SxxS motif drives assembly of the transmembrane domains of Toll-like
      receptor 4.
AB  - Like all members of the Toll-like receptor (TLR) family, TLR4 comprises of a
      large ectodomain (ECD) involved in ligand recognition at the cell-surface, and a
      cytosolic Toll/interleukin-1 receptor (TIR) signalling domain, linked by a lipid
      membrane-anchored transmembrane (TM) domain (TMD). Binding of immunostimulatory
      pathogen-associated molecular patterns (PAMPs) such as bacterial
      lipopolysaccharide (LPS) to myeloid differentiation factor 2 (MD-2) coreceptor
      complexed TLR4 leads to its dimerization, resulting in productive juxtaposition
      of TIR domains and the initiation of pro-inflammatory innate immune responses.
      Whilst the process of PAMP recognition is relatively well understood, thanks to
      numerous high-resolution crystallographic structures of ECDs, the mechanism by
      which such recognition is translated into TMD dimerization and activating
      conformational changes is less clear. Based on available biophysical and
      biochemical experimental data, ab initio modelling, and multiscale molecular
      dynamics (MD) simulations entailing a total of >13MUs and >200MUs of atomistic
      and coarse-grained sampling, respectively, we investigate the structural basis
      for TLR4 TMD dimerization within a biologically relevant lipid membrane
      environment. A key polar-xx-polar (637SxxS640) motif is shown to drive
      association of the TLR4 TMDs, and to maintain a flexible interface, which may be
      disrupted by selected point mutations. Furthermore, MD simulations of various
      TMD+ECD constructs have been used to investigate the coupling between domains,
      revealing that flexible linkers abrogate dimerization via aggregation of ECDs at
      the membrane surface, explaining previous biochemical observations. These results
      improve our understanding of the assembly and signalling mechanisms of TLR4, and
      pave the way for rational structure-based development of membrane-associated
      immunomodulatory molecules.

PMID- 28739293
TI  - Psychological recovery after intensive care: Outcomes of a long-term quasi
      experimental study of structured nurse-led follow-up.
AB  - OBJECTIVES: To compare psychological recovery of patients receiving structured
      nurse-led follow-up and patients receiving usual care after intensive care
      discharge. DESIGN: Quasi-experimental study. SETTING: Single centre, university
      hospital, mixed intensive care patient population. MAIN OUTCOME MEASURES:
      Symptoms of post-traumatic stress disorder, anxiety and depression measured three
      and four times over 12 months after intensive care discharge. Disturbing memories
      of the intensive care stay and psychological reactions (that one's life was in
      danger, threat to physical integrity, intense fear, helplessness, horror) three
      months after intensive care. A mixed effect model tested differences between the
      groups over time and regression model predicted post-traumatic stress at three
      months. RESULTS: The experimental group had significantly more symptoms of post
      traumatic stress and anxiety than the control group over the 12 months. Patients
      from both groups had severe symptoms of post-traumatic stress. Patients with post
      traumatic stress at three months had disturbing memories and psychological
      reactions. CONCLUSION: The structured nurse-led follow-up did not improve
      patients' measured outcomes of psychological recovery after intensive care.
      Patients with severe symptoms of post-traumatic stress are of concern. Emphasis
      needs to be placed on disturbing memories of the intensive care stay and
      psychological reactions when constructing intensive care nurse-led follow-up.

PMID- 28739294
TI  - Polycyclic aromatic hydrocarbons and female reproductive health: A scoping
      review.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a class of common persistent
      environmental pollutants found in water, air, soil, and plants and can be
      released by natural sources. However, the majority of atmospheric PAHs are from
      vehicular emissions, coal-burning plants, and the production and use of petroleum
      derived substances. Exposure to PAHs has been implicated in cancer and other
      diseases, including reproductive disorders. This scoping review is a preliminary
      step that explores the utility and feasibility of completing a systematic review
      evaluating the effect of PAHs on female reproduction. We performed literature
      searches in PubMed, Web of Science, and Scopus, then screened, identified, and
      categorized relevant studies. Our results identified fertility and
      pregnancy/fetal viability as outcomes with sufficient research for systematic
      review. In addition to presenting the relevant studies, the review identifies
      data gaps, and provides the groundwork to develop the most appropriate research
      questions for systematic review.

PMID- 28739295
TI  - Dispositional mindfulness and reward motivated eating: The role of emotion
      regulation and mental habit.
AB  - Evidence regarding the effectiveness of mindfulness based interventions (MBIs)
      for eating disorders, weight management and food craving is emerging and further
      studies are required to understand the underlying mechanisms of MBIs in these
      domains. The current study was designed to establish the role of specific
      mechanisms underlying the putative relationship between mindfulness and reward
      motivated eating. We predicted that mindfulness would be negatively related to
      features of reward motivated eating and that this association would be mediated
      by emotion regulation and habitual negative self-thinking. A cross-sectional
      survey measuring uncontrolled and emotional eating, mindfulness, emotion
      regulation and habitual negative self-thinking was completed by female and male
      meditators and non-meditators (N = 632). Lower levels of dispositional
      mindfulness were associated with difficulties in emotion regulation, habitual
      negative self-thinking and both emotional and uncontrolled eating. Difficulties
      in emotion regulation significantly mediated the mindfulness-uncontrolled eating
      relationship. Habitual negative self-thinking significantly mediated the
      mindfulness-emotional eating relationship. Participants with meditation
      experience reported greater levels of dispositional mindfulness, fewer
      difficulties with emotion regulation and habitual negative self-thinking and
      reduced uncontrolled eating tendencies, compared to non-meditators. The findings
      suggest that MBIs designed to change reward motivated eating and weight control
      should focus on emotion regulation and mental habits as underlying mechanisms.

PMID- 28739296
TI  - Retraction notice to "Recent advances in cardiac regeneration: Stem cell,
      biomaterial and growth factors" [Biomed. Pharmacother. 87 (2017) 37-45].

PMID- 28739297
TI  - The impact of insulin dependence on short-term postoperative complications in
      diabetic patients undergoing total shoulder arthroplasty.
AB  - BACKGROUND: The number of total shoulder arthroplasty (TSA) procedures performed
      is steadily increasing, and it is important to characterize predictors of
      postoperative complications for risk assessment models. Whereas diabetes has been
      associated with increased morbidity after TSA, the impact of insulin dependence
      on the risk profile of diabetic patients has not been described. METHODS: The
      National Surgical Quality Improvement Program database from 2011-2014 was used to
      identify 5918 TSA cases. Patients were categorized as non-diabetes mellitus (non
      DM), non-insulin-dependent diabetes mellitus (NIDDM), or insulin-dependent
      diabetes mellitus (IDDM). Thirty-day postoperative complication rates, length of
      stay (LOS), and readmission rates were compared across the diabetes groups.
      Multivariable logistic regression adjusting for demographics and comorbidity
      burden was performed to determine the independent association between insulin
      dependence and postoperative outcomes. RESULTS: In bivariate analysis, NIDDM and
      IDDM were associated with multiple postoperative complications, including stroke,
      sepsis, wound complications, blood transfusion, and extended LOS. With
      multivariable logistic regression, however, NIDDM patients did not have
      significantly greater odds of any study end point relative to non-DM patients.
      IDDM patients had significantly greater odds for having any postoperative
      complication (odds ratio [OR], 1.53), stroke (OR, 13.63), blood transfusion (OR,
      1.67), and extended LOS (OR, 1.38). CONCLUSIONS: After adjustment for
      demographics and comorbidity burden, NIDDM patients had risk profiles similar to
      those of non-DM patients. IDDM was an independent predictor of multiple
      postoperative complications. Insulin dependence should be considered in the
      preoperative risk assessment of diabetic patients undergoing TSA.

PMID- 28739298
TI  - Guidelines for humeral subluxation cutoff values: a comparative study between
      conventional, reoriented, and three-dimensional computed tomography scans of
      healthy shoulders.
AB  - BACKGROUND: The humeral subluxation index (HSI) is frequently assessed on
      computed tomography (CT) scans in conditions of the shoulder characterized by
      humeral displacement. An arbitrarily set HSI cutoff value of 45% for anterior
      subluxation and 55% for posterior subluxation has been widely accepted. We
      studied whether mean values and thresholds of humeral subluxation, in relation to
      the glenoid and scapula, were influenced by different imaging modalities.
      METHODS: The HSIs referenced to the scapula (SHSI) and glenoid (GHSI) were
      compared between conventional CT scans, CT scans reoriented into the
      corresponding reference plane (ie, scapular plane for the SHSI and glenoid center
      plane for the GHSI), and 3-dimensional (3D) CT reconstructions of 120 healthy
      shoulders. The 95% normal range determined the cutoff values of humeral
      subluxation. RESULTS: The SHSI thresholds for conventional, reoriented, and 3D CT
      scans were 33%-61%, 44%-68%, and 49%-61%, respectively. A different mean SHSI was
      found for each imaging modality (conventional, 47%; reoriented, 56%; 3D, 55%; P
      <= .014), with the conventional SHSI showing an underestimation in 89% of the
      cases. GHSI thresholds for conventional, reoriented, and 3D CT scans were 40%
      61%, 44%-56%, and 46%-54%, respectively. The mean GHSI did not differ between
      each imaging modality (conventional, 51%; reoriented, 50%; 3D, 50%; P = .146).
      CONCLUSIONS: The SHSI and GHSI are susceptible to different imaging modalities
      with consequently different cutoff values. The redefined HSI cutoff values guide
      physicians in the evaluation of humeral subluxation in conditions characterized
      by humeral displacement, depending on the available image data.

PMID- 28739299
TI  - Surgical treatment of acute type V acromioclavicular joint dislocations in
      professional athletes: an anatomic ligament reconstruction with synthetic implant
      augmentation.
AB  - BACKGROUND: Most acromioclavicular (AC) joint injuries occur in men in their
      third decade of life during high-speed or high-impact body contact sports. The
      management of acute complete AC joint dislocation is surgical. Current surgical
      techniques include anatomic reconstruction of the main restraints of the AC joint
      and aim to improve functional outcomes and to reduce the complication rate.
      METHODS: We present 10 cases of acute type V AC joint dislocation in professional
      athletes treated surgically with anatomic reconstruction of the coracoclavicular
      and AC ligaments and augmentation with the use of a synthetic polyester tape. The
      minimum follow-up of the patients was 2 years (mean, 48 months; range, 24-86
      months). The postoperative functional outcome was assessed at 1 year and 2 years
      using the Constant-Murley, American Shoulder and Elbow Surgeons, and modified
      University of California-Los Angeles scoring systems. RESULTS: In all cases, the
      postoperative scores were significantly improved (P < .005 in all comparisons
      with the preoperative scores), and all patients returned to their preinjury high
      level of activity 6 months postoperatively. Radiographs at 1 month and 6 months
      revealed the maintenance of reduction. There were no complications. CONCLUSION:
      According to the results of our series of patients, demanding cases of acute AC
      joint dislocation Rockwood type V, in professional athletes, require anatomic
      fixation of both coracoclavicular and AC ligaments for return to sports as soon
      as possible and at the preinjury level of performance.

PMID- 28739300
TI  - The critical shoulder angle is associated with osteoarthritis in the shoulder but
      not rotator cuff tears: a retrospective case-control study.
AB  - BACKGROUND: In 2013 Moor et al introduced the concept of the critical shoulder
      angle (CSA) and suggested that an abnormal CSA was a leading factor in
      development of rotator cuff tear (RCT) and osteoarthritis (OA) of the shoulder.
      This study assessed whether the CSA was associated with RCT and OA and tested the
      inter- and intrarater reliability of the CSA when measuring RCT and OA. MATERIALS
      AND METHODS: The study was performed as a retrospective case-control study. The
      cases comprised 2 groups: 97 patients with RCT and 87 patients with OA. The
      controls were matched 3:1, by age and sex, from a population of 795 patients with
      humeral fractures. The CSA was measured as described by Moor et al. Analysis of
      the relation with CSA for RCT and OA was done by logistic regression. Models were
      fitted separately for RCT and OA and used the controls matched to the respective
      cases. Inter- and intrarater reliability was determined by measuring the
      intraclass correlation coefficient and minimal detectable change. RESULTS: The
      mean CSA was 33.9 degrees  in the RCT group and 33.6 degrees  in the matched
      control group. The odds ratio for developing RCT for people with a CSA above 35
      degrees  was 1.12 (P = .63). The mean CSA in the OA group was 31.1 degrees  and
      in the matched control group 33.3 degrees . The odds ratio for developing OA for
      people with a CSA below 30 degrees  was 2.25 (P = .002). The CSA measurements
      showed strong intra- and inter-rater reliability, with intraclass correlation
      coefficient values above 0.92 and minimal detectable change values below 0.4
      degrees . CONCLUSIONS: This study did not find any association between CSA and
      RCT but did show association between CSA and OA, with a 2.25 odds ratio of
      developing OA given the patient had a CSA below 30 degrees . The results do not
      support the suggested praxis of shaving away the lateral border of the acromion
      to make the CSA smaller because it might increase the risk of developing OA
      without decreasing the risk of developing RCT. The CSA measurements showed
      excellent intra- and inter-rater reliability.

PMID- 28739301
TI  - A new PCR assay for the detection and differentiation of Babesia canis and
      Babesia vogeli.
AB  - Babesia spp. are globally distributed tick-borne protozoan parasites that infect
      the red blood cells of a wide range of vertebrate hosts, including humans.
      Diagnosis of babesiosis is often impeded by the transient presence of the
      parasites in peripheral blood, as well as by their pleomorphic nature. Given the
      reports of an expanding and, in some cases, sympatric geographical distribution
      of Babesia canis and Babesia vogeli in dogs and associated vectors, in Europe,
      the development of time-efficient and cost-effective diagnostic tools to detect
      and differentiate these two species is warranted. In this study, we designed and
      developed a novel polymerase chain reaction (PCR) assay targeting the parasite
      cytochrome c oxidase subunit 1 (cox1) gene, for the simultaneous detection and
      differentiation of B. canis and B. vogeli. The analytical sensitivity of the PCR
      was evaluated using serial dilutions of genomic DNA extracted from individual and
      artificially mixed canine blood samples infected by B. canis (3*102 infected
      erythrocytes/ml, ie/ml) and B. vogeli (2.1*101 ie/ml). The analytical specificity
      of the assay was assessed using blood samples positive for Hepatozoon canis,
      Ehrlichia canis, Anaplasma platys, Babesia microti, Babesia rossi and Theileria
      annae (syn. Babesia vulpes). The clinical specificity of the PCR assay was
      evaluated on 147 blood samples from dogs and 128 tick specimens (Dermacentor
      reticulatus and Rhipicephalus sanguineus sensu lato). Species-specific bands of
      the expected sizes (i.e., 750bp for B. canis and 450bp for B. vogeli), and two
      bands in the mixed blood samples were obtained. The PCR assay developed herein
      detected a low number of infected erythrocytes (i.e., 3*10-2B. canis, 2.1*10-2B.
      vogeli ie/ml). Of the 147 blood samples, nine (6.1%) were positive for B. canis
      and six (4.1%) for B. vogeli, whereas only one tick (D. reticulatus) was positive
      for B. canis. This PCR assay represents a rapid and reliable tool for the
      diagnosis of B. canis and B. vogeli in areas where these species occur in
      sympatry, and will assist future epidemiological investigations aimed to track
      the expanding range of these parasites.

PMID- 28739302
TI  - Comparison of the analytical and clinical performance of five tests for the
      detection of human papillomavirus genital infection.
AB  - HPV-based screening provides greater protection against cervical cancer (CC) than
      cytology-based strategies. Currently, several molecular diagnostic assays for the
      detection of human papillomavirus (HPV) are available. In this study, we analyzed
      5 different HPV testing and genotyping techniques (Hybrid Capture 2 [HC2; Qiagen,
      Hilden, Germany], AnyplexTMII HPV28 [Anyplex; Seegene, Seoul, Korea], Linear
      Array [Roche, Branchburg, NJ, USA], GP5+/6+ PCR-EIA-RH [Labo Bio-medical
      Products, Rijswijk, The Netherlands] and CLART2 [Genomica, Madrid, Spain]) in 295
      women referred to the hospital Colposcopy Clinic from 2007 to 2008 due to
      positive HPV test results or an abnormal Pap test. DNA extraction for HPV
      genotyping was performed in cervical sample specimens after Pap test and HPV
      detection by HC2. The inclusion criteria were: (1) adequate cervical sampling
      with sufficient material for the Pap test and HPV detection and genotyping, and
      (2) colposcopically-directed biopsy and/or endocervical curettage. HC2 showed the
      highest sensitivity for high-grade squamous intraepithelial lesion and CC (HSIL+)
      detection (96.1%), but all the HPV genotyping tests showed a higher specificity.
      (Anyplex 86.8%; Linear Array 86.0%; GP5+/6+ 78.8%; CLART2 76.5%). The agreement
      between HC2 results and the other techniques was similar: 82.4%, kappa=0.650 for
      Anyplex; 83.4%, kappa=0.670 for Linear Array, 79.93%, kappa=0.609 for GP5+/6+ and
      82.4%, kappa=0.654 for CLART2. HPV 16 and/or 18 infection was a risk factor for
      underlying HSIL+ in the univariate analysis. Anyplex showed the highest risk of
      underlying HSIL+ after positive HPV 16 and/or 18 tests (OR 31.1; 95% CI 12.1
      80.0).

PMID- 28739303
TI  - CpG oligonucleotides increase HBV-specific cytokine responses in whole blood and
      enhance cytokine release assay sensitivity.
AB  - BACKGROUND: Chronic hepatitis B leads to liver cirrhosis and hepatocellular
      carcinoma. To develop a therapeutic vaccine for chronic hepatitis B patients it
      is necessary to assess cellular immune responses to hepatitis B virus (HBV)
      antigens. We investigated the potential of toll-like receptor (TLR) 9 agonists,
      i.e. CpG oligonucleotides, as costimulators to increase diagnostic sensitivity
      and specificity of our HBV- specific cytokine release assay. METHODS: Whole blood
      from 80 healthy individuals (n=51 hepatitis B vaccinated, n=29 unvaccinated) was
      stimulated with hepatitis B surface antigen (HBsAg) or hepatitis B core antigen
      (HBcAg) in presence or absence of CpG oligonucleotides. IL2 and IFNgamma
      secretion in plasma was assessed using ELISA. RESULTS: CpG oligonucleotides
      specifically enhanced HBsAg-mediated IL2 (276+/-79pg/ml vs. 320+/-82pg/ml) and
      IFNgamma (77+/-35pg/ml vs. 401+/-121pg/ml) responses in whole blood. When
      IFNgamma release was considered as readout depicting the hepatitis B vaccination
      status, the according assay reached a diagnostic sensitivity of 61% without, but
      of 76% with additional CpG oligonucleotide stimulation at a diagnostic
      specificity of 90%. CONCLUSIONS: We show that innate signals mediated via TLRs
      contribute to HBV-specific cellular immune responses. CpG oligonucleotides can be
      used to make whole blood based cytokine release assays even more powerful as
      screening tools in HBV immunology.

PMID- 28739304
TI  - Role of NADPHox/Rho-kinase signaling in the cyclosporine-NSAIDs interactions on
      blood pressure and baroreflexes in female rats.
AB  - AIMS: The hypertensive effect of the immunosuppressant drug cyclosporine (CSA) is
      paralleled, and probably triggered, by impaired arterial baroreceptor sensitivity
      (BRS). Here we asked if these effects of CSA are influenced by co-administration
      of nonsteroidal antiinflammatory drugs (NSAIDs) and if the oxidative NADPH
      oxidase (NADPHox)/Rho-kinase (ROCK) pathway mediates this interaction. MATERIALS
      AND METHODS: Female rats were treated for 10days with CSA (25mg/kg/day),
      diclofenac (DIC, COX-1/COX-2 inhibitor, 1mg/kg/day), celecoxib (COX-2 inhibitor,
      10mg/kg/day), or their combinations. Baroreflex curves relating changes in heart
      rate (HR) to increases or decreases in blood pressure (BP) evoked by
      phenylephrine (PE) and sodium nitroprusside (SNP), respectively, were constructed
      and slopes of the curves were taken as measures of BRS. KEY FINDINGS: Compared
      with control rats, CSA increased BP and reduced reflex chronotropic responses as
      indicated by the significantly smaller BRSPE and BRSSNP values. Similar effects
      were observed in rats treated with diclofenac alone or combined with CSA. Whereas
      CSA hypertension was maintained after selective COX-2 inhibition by celecoxib,
      the concomitant BRS reductions were largely eliminated. NADPHox inhibition by
      diphenyleneiodonium (DPI) blunted the CSA/DIC-evoked increases and decreases in
      BP and BRSPE, respectively. By contrast, fasudil (ROCK inhibitor) had no effect
      on CSA/DIC hypertension but reversed the associated reductions in both BRSPE and
      BRSSNP. SIGNIFICANCE: Depending on the nature of the cardiovascular response,
      NADPHox and ROCK contribute variably to the worsened cardiovascular profile in
      CSA/DIC-treated rats. Further, celecoxib rather than diclofenac could be a better
      choice as an add-on therapy to CSA in autoimmune arthritic conditions.

PMID- 28739305
TI  - Melatonin as a multifunctional anti-cancer molecule: Implications in gastric
      cancer.
AB  - Gastric cancer (GC) is a predominant malignancy with a high mortality rate
      affecting a large population worldwide. The etiology of GC is multifactorial
      spanning from various genetic determinants to different environmental causes.
      Current tretaments of GC are not efficient enough and require improvements to
      minimize the adverse effects. Melatonin, a naturally occurring compound with
      known potent inhibitory effects on cancer cells is one of the major candidates
      which can be recruited herein. Here we reviewed the articles conducted on the
      therapeutic effects of melatonin in gastric cancer in various models. The results
      are classified according to different aspects of cancer pathogenesis and the
      molecular mechanisms by which melatonin exerts its effects. Melatonin could be
      used to combat GC exploiting its effects on multiple aspects of its pathogenesis,
      including formation of cancer cells, tumor growth and angiogenesis,
      differentiation and metastasis as well as enhancing the anti-tumor immunity.
      Melatonin is a pleiotropic anti-cancer molecule that affects malignant cells via
      multiple mechanisms. It has been shown to benefit cancer patients indirectly by
      reducing side effects of current therapies which have been discussed in this
      review. This field of research is still underdeveloped and may serve as an
      interesting subject for further studies aiming at the molecular mechanisms of
      melatonin and novel treatments.

PMID- 28739306
TI  - The in vitro and in vivo effects of microRNA-133a on intervertebral disc
      destruction by targeting MMP9 in spinal tuberculosis.
AB  - AIMS: We aim to investigate the role of microRNA-133a (miR-133a) in
      intervertebral disc destruction by targeting MMP9 in spinal tuberculosis (TB).
      MAIN METHODS: Rabbit models with spinal TB were established and assigned to the
      blank, miR-133a mimic, miR-133a inhibitor and negative control (NC) groups.
      Primary notochordal cells were extracted and separately transfected with miR-133a
      mimics, miR-133a inhibitor, miR-nonsense sequence control (NC), si-NC and si
      MMP9. QRT-PCR and Western blot assay were used to detect the expression of MMP-9,
      Collagen I, Collagen II and Collagen-X. Gelatin Zymography was performed to
      detect MMP9 activity. Immunohistochemistry was used to detect the expression of
      Collagen I, Collagen II and Collagen-X proteins. Osteoclast morphology and the
      number of osteoclast cells were observed after Tartrate resistant acid
      phosphatase staining. KEY FINDINGS: MMP9, Collagen-X and Collagen I expression
      and MMP9 activity were higher while the expression of Collagen II was lower in
      the miR-133a mimic group than the miR-NC group. MMP9, Collagen-X Collagen I and
      MMP9 activities were lower and Collagen II expression was higher in the miR-133a
      inhibitor group than the miR-NC group. Compared with the si-NC group, the si-MMP9
      group showed increased Collagen II expression but decreased expression of MMP9,
      Collagen-X and Collagen I and MMP9 activity. A reduced amount of osteoclast cells
      exhibited in the miR-133a mimic group while an increased number was seen in the
      miR-133a inhibitor group compared to the blank group. SIGNIFICANCE: MiR-133a
      could inhibit Collagen degradation by down-regulating MMP-9 expression to
      attenuate the destructive effects of spinal TB on intervertebral disc.

PMID- 28739307
TI  - Conservative Treatment for Minimally Displaced Type B Periprosthetic Femoral
      Fractures.
AB  - BACKGROUND: Surgical treatment has been invariably indicated for Vancouver type B
      periprosthetic femoral fractures (PFFs), which involve femoral diaphysis around
      stem. We evaluated the outcomes of nonoperative management in patients with
      minimally displaced type B PFFs around cementless stem. METHODS: From October
      2009 to March 2016, 60 type B PFFs were treated at 1 institution. Among them, 19
      minimally (<5 mm) displaced PFFs (31.7%, 19/60), which occurred around cementless
      stems, were treated nonsurgically with use of teriparatide. There were 6 men and
      13 women. The mean age was 77.9 years (range, 51-98 years) at the time of PFF.
      The femoral stem was stable (type B1) in 11 patients and unstable (type B2) in 8.
      Teriparatide was injected from 1 to 4 months (mean, 3.2 months). We evaluated
      time to radiologic union and union rate. RESULTS: A successful union was obtained
      in 16 patients (89.5%, 17/19) at 2 to 6 months (mean, 3.5 months). The union rate
      was 100% (11/11) in type B1 fractures and 75% (6/8) in type B2 fractures.
      CONCLUSION: Our study showed that conservative treatment is feasible for the
      cases of type B1 minimally displaced periprosthetic fractures, and it may also be
      considered as an alternative option for type B2 minimally displaced
      periprosthetic fractures.

PMID- 28739308
TI  - Risk of Surgical Site Infection in Elective Hip and Knee Replacements After
      Confirmed Eradication of MRSA in Chronic Carriers.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is globally
      endemic and is a leading cause of surgical site infection (SSI). The purpose of
      this study was to evaluate the incidence of SSI in MRSA carriers undergoing
      elective hip or knee arthroplasty, who had confirmed eradication and to compare
      it with incidence of SSI in non-MRSA carriers. METHODS: This is a retrospective
      analysis of 6613 patients who underwent elective total hip arthroplasty (THA; n =
      3347) and total knee arthroplasty (TKA; n = 3266) at our institution. A cohort of
      patients who were preoperatively colonized with MRSA was identified. We compared
      the infection rates with non-MRSA carriers. RESULTS: We had a colonization rate
      of 1.3% (83 patients). A total of 79 patients had confirmed eradication of
      carrier status before surgical intervention. Of these, 38 were THAs and 41 were
      TKAs. Five of 79 patients (6.32%; 95% confidence interval [CI]: 2.35%-14.79%) had
      "deep SSI" within 1 year of surgery. There were 2 MRSA infections in THAs
      (relative risk 4.46; 95% CI: 1.12-17.82). There were 2 MRSA and 1 methicillin
      sensitive Staphylococcus aureus infections in TKAs (relative risk 5.61; 95% CI:
      1.81-17.38). A significant statistical difference in infection rates from MRSA
      negative control group was noted, which had a deep sepsis rate of 1.17% in THAs
      and 1.3% in TKAs over the same period. CONCLUSION: In spite of a selective
      treatment program for carriers and confirmed eradication, there is still a
      significantly increased risk of SSI in MRSA-colonized patients undergoing hip or
      knee arthroplasties.

PMID- 28739309
TI  - Preoperative Symptoms in Femoroacetabular Impingement Patients Are More Related
      to Mental Health Scores Than the Severity of Labral Tear or Magnitude of Bony
      Deformity.
AB  - BACKGROUND: The purpose of this study was to determine the relationships between
      patient factors, mental health status, the condition of the local tissue,
      magnitude of bony deformity, and preoperative symptoms in a series of
      femoroacetabular impingement (FAI) patients. METHODS: From our prospective
      outcomes registry, we identified 64 patients with arthroscopically-treated labral
      tears and cam deformities. We assessed the correlations between patient factors
      (age, sex, body mass index, level of education), surgical findings (size of
      labral tear, presence of chondral lesions), mental health factors (VR-12 mental
      component score [MCS], depression, and preoperative use of psychotropic and/or
      opioid drugs), magnitude of FAI deformity (alpha and lateral center edge angles),
      and preoperative hip dysfunction and osteoarthritis outcome score (HOOS)
      subscales. Patient factors, surgical and radiographic findings, and preoperative
      HOOS scores were compared between patients with low and high MCS. RESULTS:
      Neither hip pathology nor patient-related factors significantly correlated with
      HOOS scores. On the contrary, MCS significantly correlated with HOOS symptom (rho
      = 0.45, P < .001) and pain scores (rho = 0.52, P < .001). Low MCS patients had
      significantly lower preoperative scores for all 5 HOOS subscales (P <= .002) and
      more frequent chondral lesions and comorbid depression (P <= .01). CONCLUSION:
      Symptom severity was significantly more related to mental health status than
      either the size of labral tear or FAI deformity. Patients with low MCS had
      significantly worse preoperative pain and self-reported function, and a greater
      prevalence of concomitant chondral lesions. Future studies are necessary to
      determine if earlier surgical treatment or preoperative psychological and/or pain
      coping interventions may improve outcomes for those with low MCS.

PMID- 28739310
TI  - Identification of new TSGA10 transcript variants in human testis with conserved
      regulatory RNA elements in 5'untranslated region and distinct expression in
      breast cancer.
AB  - Testis specific gene antigen 10 (TSGA10) is a cancer testis antigen involved in
      the process of spermatogenesis. TSGA10 could also play an important role in the
      inhibition of angiogenesis by preventing nuclear localization of HIF-1alpha.
      Although it has been shown that TSGA10 messenger RNA (mRNA) is mainly expressed
      in testis and some tumors, the transcription pattern and regulatory mechanisms of
      this gene remain largely unknown. Here, we report that human TSGA10 comprises at
      least 22 exons and generates four different transcript variants. It was
      identified that using two distinct promoters and splicing of exons 4 and 7
      produced these transcript variants, which have the same coding sequence, but the
      sequence of 5'untanslated region (5'UTR) is different between them. This is
      significant because conserved regulatory RNA elements like upstream open reading
      frame (uORF) and putative internal ribosome entry site (IRES) were found in this
      region which have different combinations in each transcript variant and it may
      influence translational efficiency of them in normal or unusual environmental
      conditions like hypoxia. To indicate the transcription pattern of TSGA10 in
      breast cancer, expression of identified transcript variants was analyzed in 62
      breast cancer samples. We found that TSGA10 tends to express variants with
      shorter 5'UTR and fewer uORF elements in breast cancer tissues. Our study
      demonstrates for the first time the expression of different TSGA10 transcript
      variants in testis and breast cancer tissues and provides a first clue to a role
      of TSGA10 5'UTR in regulation of translation in unusual environmental conditions
      like hypoxia.

PMID- 28739311
TI  - [Constrictive pericarditis and single coronary artery: Rare presentation].

PMID- 28739312
TI  - Editorial Commentary: Indications for catheter ablation of ventricular
      tachycardia in the modern era.

PMID- 28739314
TI  - Concussion Rates in U.S. Middle School Athletes, 2015-2016 School Year.
AB  - INTRODUCTION: Concussion incidence estimates in middle school sports settings are
      limited. This study examines concussion incidence in nine U.S. middle schools
      during the 2015-2016 school year. METHODS: Concussion data originated from nine
      public middle schools in Prince William County, Virginia, during the 2015-2016
      school year. Certified athletic trainers collected concussion and athlete
      exposure (AE) data in school-sanctioned games and practices in boys' baseball,
      basketball, football, soccer, track, and wrestling; and girls' basketball,
      cheerleading, soccer, softball, track, and volleyball. Athletic trainers also
      acquired data on non-school sanctioned sport concussions. In 2017, concussion
      rates were calculated per 1,000 AEs. Injury rate ratios with 95% CIs compared
      rates between games and practices and by sex. RESULTS: Overall, 73 concussions
      were reported, of which 21.9% were from non-school sanctioned sport settings. The
      57 remaining game and practice concussions were reported during 76,384 AEs, for a
      concussion rate of 0.75/1,000 AEs. Football had the highest concussion rate
      (2.61/1,000 AEs). Concussion rates were higher in games versus practices (injury
      rate ratio=1.83, 95% CI=1.06, 3.15), and in girls versus boys in sex-comparable
      sports, i.e., baseball/softball, basketball, soccer, and track (injury rate
      ratio=3.73, 95% CI=1.24, 11.23). CONCLUSIONS: Current findings parallel those
      found in high school and college sports settings in that higher concussion rates
      were reported in girls and competitions. However, concussion rates exceeded those
      recently reported in high school and youth league settings, highlighting the need
      for continued research in the middle school sports setting. Given that one in
      five concussions were from non-school sanctioned sport settings, prevention
      efforts in middle school sports settings should consider sport and non-sport at
      risk exposure.

PMID- 28739313
TI  - Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment.
AB  - The amyloidoses are a group of systemic diseases characterized by organ
      deposition of misfolded protein fragments of diverse origins. The natural history
      of the disease, involvement of other organs, and treatment options vary
      significantly based on the protein of origin. In AL amyloidosis, amyloid protein
      is derived from immunoglobulin light chains, and most often involves the kidneys
      and the heart. ATTR amyloidosis is categorized as mutant or wild-type depending
      on the genetic sequence of the transthyretin (TTR) protein produced by the liver.
      Wild-type ATTR amyloidosis mainly involves the heart, although the reported
      occurrence of bilateral carpal tunnel syndrome, spinal stenosis and biceps tendon
      rupture in these patients speaks to more generalized protein deposition. Mutant
      TTR is marked by cardiac and/or peripheral nervous system involvement. Cardiac
      involvement is associated with symptoms of heart failure, and dictates the
      clinical course of the disease. Cardiac amyloidosis can be diagnosed
      noninvasively by echocardiography, cardiac MRI, or nuclear scintigraphy.
      Endomyocardial biopsy may be needed in the case of equivocal imaging findings or
      discordant data. Treatment is aimed at relieving congestive symptoms and
      targeting the underlying amyloidogenic process. This includes anti-plasma cell
      therapy in AL amyloidosis, and stabilization of the TTR tetramer or inhibition of
      TTR protein production in ATTR amyloidosis. Cardiac transplantation can be
      considered in highly selected patients in tandem with therapy aimed at
      suppressing the amyloidogenic process, and appears associated with durable long
      term survival.

PMID- 28739315
TI  - Combination Therapy of Radiotherapy and Anti-PD-1/PD-L1 Treatment in Non-Small
      cell Lung Cancer: A Mini-review.
AB  - Immune checkpoint inhibitors against programmed cell death-1 (PD-1) or programmed
      cell death-ligand 1 (PD-L1) are a standard pharmacologic therapy for patients
      with non-small-cell lung cancer (NSCLC). Substantial data have accumulated in
      recent years showing that radiotherapy combined with immunotherapy is more
      effective than monotherapy alone. Preclinical studies have shown that PD-L1
      expression is upregulated on tumor cells after radiotherapy, resulting in the
      synergistically enhanced antitumor effect of irradiation and PD-L1 blockade. In
      the clinical setting, patients receiving radiotherapy before anti-PD-1 treatment
      have had a significantly better prognosis than those who have not undergone
      radiotherapy. In the present report, we reviewed previous studies of the
      combination of radiotherapy and anti-PD-1/PD-L1 treatment for NSCLC. In addition,
      we report our case of a patient whose PD-L1 expression gradually increased in
      brain metastases from NSCLC after repeated radiotherapy. In the perspectives
      portion, we focused on the questions of how to integrate radiotherapy into anti
      PD-1/PD-L1 agent regimens and described several ongoing clinical trials.

PMID- 28739316
TI  - Validation of the Disease-Specific GPA for Patients With 1 to 3 Synchronous Brain
      Metastases in Newly Diagnosed NSCLC.
AB  - BACKGROUND: The disease-specific graded prognostic assessment (DS-GPA) for brain
      metastases is a powerful prognostic tool but has not been validated for patients
      with synchronous brain metastases (SBM) in newly diagnosed non-small-cell lung
      cancer (NSCLC). PATIENTS AND METHODS: We identified patients with newly diagnosed
      NSCLC with 1 to 3 SBM treated with stereotactic radiosurgery (SRS) between 1997
      and 2012. We included patients whose brain metastases were treated with SRS alone
      or combined SRS and whole-brain radiotherapy (WBRT). Patients were stratified
      according to NSCLC DS-GPA to evaluate the accuracy of survival estimates.
      RESULTS: One hundred sixty-four patients were treated with either SRS alone (n =
      85; 52%) or SRS and WBRT (n = 79; 48%). Median overall survival (OS) stratified
      according to DS-GPA of 0 to 1, 1.5 to 2, 2.5 to 3, and 3.5 to 4 were 2.8, 6.7,
      9.8, and 13.2 months, respectively, consistent with OS reported for brain
      metastases in NSCLC DS-GPA (3.0, 6.5, 11.3, and 14.8 months, respectively). No
      difference in median progression-free survival or OS was noted with combined use
      of SRS and WBRT: 6.0 versus 6.1 months (P = .81) and 8.5 versus 9.1 months (P =
      .093), respectively. In multivariable analysis, Karnofsky performance status
      (hazard ratio [HR], 0.98; P = .008), extracranial metastases (HR, 0.498; P =
      .0003), squamous histology (HR, 1.81; P = .02), and number of brain metastases (2
      vs. 1; HR, 1.504; P = .04, and 3 vs. 1; HR, 1.66; P = .05) were significant
      predictors of OS. CONCLUSION: The DS-GPA accurately estimates the prognosis of
      patients with SBM in newly diagnosed NSCLC. Patients with synchronous brain
      metastasis in newly diagnosed NSCLC should be carefully stratified for
      consideration of aggressive therapy.

PMID- 28739317
TI  - Comparative Effectiveness and Resource Usage in Patients Receiving First-line
      Taxol-based Chemotherapy for Stage IV NSCLC.

PMID- 28739318
TI  - Impact of biannual treatment with fluoride varnish on tooth-surface-level caries
      progression in children aged 1-3 years.
AB  - OBJECTIVE: This study describes caries progression at tooth-surface level in
      children from 1 to 3 years of age and the impact of biannual treatment with
      fluoride varnish. METHODS: Children who participated in a cluster-randomized
      controlled trial and had shown signs of dental caries were included in this study
      (n=801). International Caries Detection and Assessment System (ICDAS) was used to
      classify dental caries. The present study compared children receiving a standard
      yearly intervention to children receiving the same standard preventive
      intervention supplemented with an application of fluoride varnish every half
      year. RESULTS: The maxillary incisors were the first teeth to develop cavitation
      (ICDAS 3-6) and also mostly affected. Further analyses focusing on maxillary
      incisors buccal surfaces showed that sound surfaces had least progression and
      that progression to extensive decay was more common in teeth that had exhibited
      moderate decay. A summarizing progression index (PI) was calculated for the
      buccal surfaces of the maxillary incisors. Between 1 and 2 years of age PI was
      26% and between 2 and 3 years of age PI was 21%. The progression on buccal
      incisors and on occlusal first primary molars did not differ between intervention
      groups (p<=0,05). CONCLUSION: No impact on caries progression for biannual
      treatment with fluoride varnish was found. CLINICAL SIGNIFICANCE: Using fluoride
      varnish as a complement to standard intervention in toddlers did not add in the
      prevention of dental caries or its progression. The education of parents in the
      use fluoride toothpaste as they start brushing the teeth of their children is
      essential.

PMID- 28739319
TI  - The effect of prosthetic rehabilitation and simple dietary counseling on food
      intake and oral health related quality of life among the edentulous individuals:
      A randomized controlled trial.
AB  - OBJECTIVE: To investigate the combined effect of complete denture renewal and
      simple dietary advice. METHODS: A randomized controlled trial was performed with
      edentulous patients who required new complete dentures. All participants received
      complete denture treatment. In addition, the intervention group received dietary
      advice in a pamphlet form, while the control group received advice pertaining to
      the care and maintenance of the dentures. The advice was given by dentists for
      each group. The participants' food intake was assessed at baseline and 3 months
      after intervention using a diet history questionnaire and an oral health related
      quality of life assessment measured using the Japanese version of the Oral Health
      Impact Profile for edentulous people (OHIP-EDENT-J). RESULTS: Among 70
      participants who were randomized, 62 participants finished all parts of this
      trial. At baseline, there was no significant difference in the food intake
      between the two groups. At the 3-month assessment, the intervention group showed
      significantly greater intake of chicken (P=0.013), fish with bones (P=0.012), and
      carrots and pumpkins (P=0.025) compared to the control group. However, at
      baseline and at the 3-month assessment, there was no significant difference in
      the OHIP-EDENT-J scores between the groups, but the OHIP-EDENT-J scores
      significantly improved for both groups at the 3-month assessment. There were more
      significant improved dimensions of OHIP-EDENT-J in the intervention group than in
      the control group at the 3-month assessment. CONCLUSIONS: Simple dietary advice
      combined with complete denture treatment could improve food intake of edentulous
      patients. CLINICAL SIGNIFICANCE: The present study suggests that brief dietary
      advice provided by dentists can improve food intake of edentulous elderly. This
      simply diet advice is much easier compared to customized forms, might enable
      normal dentists provide patients it. The result of this study broadens
      possibility of nutritional counseling in daily clinical practice.

PMID- 28739320
TI  - Immediate implant placement into posterior sockets with or without buccal bone
      dehiscence defects: A retrospective cohort study.
AB  - OBJECTIVES: To evaluate bone reconstruction and soft tissue reactions at
      immediate implants placed into intact sockets and those with buccal bone
      dehiscence defects. METHODS: Fifty-nine internal connection implants from four
      different manufacturers were immediately placed in intact sockets(non-dehiscence
      group, n=40), and in alveoli with buccal bone dehiscence defects: 1) Group 1(n=
      N10), the defect depth measured 3-5 mm from the gingival margin. 2) Group 2(n=9),
      the depth ranged from 5mm to 7mm. The surrounding bony voids were grafted with
      deproteinized bovine bone mineral (DBBM) particles. Cone beam computed
      tomography(CBCT) was performed immediately after surgery (T1), and at 6 months
      later(T2). Radiographs were taken at prosthesis placement and one year
      postloading(T3). Soft tissue parameters were measured at baseline (T0),
      prosthesis placement and T3. RESULTS: No implants were lost during the
      observation period. For the dehiscence groups, the buccal bone plates were
      radiographically reconstructed to comparable horizontal and vertical bone volumes
      compared with the non-dehiscence group. Marginal bone loss occurred between the
      time of final restoration and 1-year postloading was not statistically
      different(P=0.732) between groups. Soft tissue parameters did not reveal inferior
      results for the dehiscence groups. CONCLUSIONS: Within the limitations of this
      study, flapless implant placement into compromised sockets in combination with
      DBBM grafting may be a viable technique to reconstitute the defected buccal bone
      plates due to space maintenance and primary socket closure provided by healing
      abutments and bone grafts. CLINICAL SIGNIFICANCE: Immediate implants and DBBM
      grafting without using membranes may be indicated for sockets with buccal bone
      defects.

PMID- 28739321
TI  - Preventing Intravenous Contrast Extravasation in CT: A Simple Solution.

PMID- 28739322
TI  - Reconsidering the Value of Gonadal Shielding During Abdominal/Pelvic Radiography.

PMID- 28739323
TI  - The Medical Physicist's Role in Radiation Optimization.

PMID- 28739324
TI  - Reaction-based small-molecule fluorescent probes for dynamic detection of ROS and
      transient redox changes in living cells and small animals.
AB  - Dynamic detection of transient redox changes in living cells and animals has
      broad implications for human health and disease diagnosis, because intracellular
      redox homeostasis regulated by reactive oxygen species (ROS) plays important role
      in cell functions, normal physiological functions and some serious human diseases
      (e.g., cancer, Alzheimer's disease, diabetes, etc.) usually have close
      relationship with the intracellular redox status. Small-molecule ROS-responsive
      fluorescent probes can act as powerful tools for dynamic detection of ROS and
      redox changes in living cells and animals through fluorescence imaging
      techniques; and great advances have been achieved recently in the design and
      synthesis of small-molecule ROS-responsive fluorescent probes. This article
      highlights up-to-date achievements in designing and using the reaction-based
      small-molecule fluorescent probes (with high sensitivity and selectivity to ROS
      and redox cycles) in the dynamic detection of ROS and transient redox changes in
      living cells and animals through fluorescence imaging.

PMID- 28739325
TI  - D242N, a KV7.1 LQTS mutation uncovers a key residue for IKs voltage dependence.
AB  - KV7.1 and KCNE1 co-assemble to give rise to the IKs current, one of the most
      important repolarizing currents of the cardiac action potential. Its relevance is
      underscored by the identification of >500 mutations in KV7.1 and, at least, 36 in
      KCNE1, that cause Long QT Syndrome (LQTS). The aim of this study was to
      characterize the biophysical and cellular consequences of the D242N KV7.1
      mutation associated with the LQTS. The mutation is located in the S4
      transmembrane segment, within the voltage sensor of the KV7.1 channel, disrupting
      the conserved charge balance of this region. Perforated patch-clamp experiments
      show that, unexpectedly, the mutation did not disrupt the voltage-dependent
      activation but it removed the inactivation and slowed the activation kinetics of
      D242N KV7.1 channels. Biotinylation of cell-surface protein and co
      immunoprecipitation experiments revealed that neither plasma membrane targeting
      nor co-assembly between KV7.1 and KCNE1 was altered by the mutation. However, the
      association of D242N KV7.1 with KCNE1 strongly shifted the voltage dependence of
      activation to more depolarized potentials (+50mV), hindering IKs current at
      physiologically relevant membrane potentials. Both functional and computational
      analysis suggest that the clinical phenotype of the LQTS patients carrying the
      D242N mutation is due to impaired action potential adaptation to exercise and, in
      particular, to increase in heart rate. Moreover, our data identify D242
      aminoacidic position as a potential residue involved in the KCNE1-mediated
      regulation of the voltage dependence of activation of the KV7.1 channel.

PMID- 28739326
TI  - Solubility, volumetric and compressibility properties of acetaminophen in some
      aqueous solutions of choline based deep eutectic solvents at T=(288.15 to 318.15)
      K.
AB  - Deep eutectic solvents (DESs) as a new class of green solvents have been used to
      overcome the low solubility of drugs during the recent years. In this work, the
      effect of some DESs containing choline chloride as hydrogen bond acceptor and
      urea, oxalic acid and malonic acid as hydrogen bond donors have been studied on
      acetaminophen (ACP) solubility at temperature ranges (298.15 to 313.15) K. The
      results indicate that the solubility of ACP increase with increasing
      concentration of DES and at higher temperatures and the DES containing malonic
      acid have a greater impact on the solubility of acetaminophen. The solubility
      data were correlated by the modified Apelblat, lambdah (Buchowski) and Yalkowsky
      models which Apelblat model is more consistent with experimental data. In
      addition, to elucidate the interactions between the components, the thermodynamic
      properties including volumetric, compressibility properties have been
      investigated using density and speed of sound measurements at T=(288.15 to
      318.15K). The calculated thermodynamic parameters values confirm the strong
      solute - solvent interactions between ACP - DESs that is in agreement with
      solubility data.

PMID- 28739327
TI  - Patterns of Use of Human Papillomavirus and Other Adolescent Vaccines in the
      United States.
AB  - PURPOSE: The purpose of the study was to describe the patterns of use of
      universally recommended adolescent vaccines in the United States. METHODS: We
      identified 11-year-olds using the MarketScan insurance claims database (2009
      2014). Human papillomavirus (HPV), tetanus-diphtheria-acellular pertussis (Tdap),
      and meningococcal (MenACWY) vaccination claims were identified using diagnosis
      and procedure codes. Generalized linear models estimated vaccination incidence
      rates and correlates of adolescent vaccination and timely vaccination. RESULTS:
      Among 1,691,223 adolescents, receipt of Tdap (52.1%) and MenACWY (45.8%)
      vaccinations exceeded receipt of HPV vaccination (18.4%). While both sexes had
      similar Tdap and MenACWY vaccination proportions, girls received HPV vaccination
      more frequently than boys (21.9% vs. 15.1%). Adolescents received HPV vaccination
      later (mean age: 11.8 years) than Tdap or MenACWY vaccination (mean age: 11.2
      years for both). Half of vaccinated adolescents received Tdap and MenACWY
      vaccination only; however, coadministration with HPV vaccine increased with birth
      cohort. Western adolescents had the highest incidence rates of HPV vaccination,
      and Southern adolescents had the lowest. Rural adolescents were less likely than
      urban adolescents to receive each vaccination except in the Northeast, where they
      were more likely to receive HPV vaccination (incidence rate ratio: 1.09, 95%
      confidence interval: 1.2005-1.13). Timely HPV vaccination was associated with
      female sex, urbanicity, Western residence, and later birth cohort. CONCLUSIONS:
      HPV vaccination occurred later than Tdap or MenACWY vaccination and was less
      frequent in boys and rural adolescents. Girls, Western and urban residents, and
      younger birth cohorts were more likely to receive timely HPV vaccination. Vaccine
      coadministration increased over time and may encourage timely and complete
      vaccination coverage.

PMID- 28739328
TI  - A Case of Oxalate Nephropathy: When a Single Cause Is Not Crystal Clear.
AB  - Hyperoxaluria can result in oxalate nephropathy with intratubular calcium oxalate
      crystallization and acute tubular injury. Primary inherited enzymatic deficiency
      or secondary causes such as excessive dietary intake, enteric increased
      absorption, or high doses of vitamin C, which is metabolized to oxalate, may
      underlie hyperoxaluria and oxalate nephropathy. We report a case of acute kidney
      injury due to oxalate nephropathy in a patient using chelating therapy with oral
      ethylenediamine tetra acetic acid (EDTA), intravenous supplementation with
      vitamin C, and chronic diarrhea and discuss the potential kidney damage these
      factors can cause in particular settings. To our knowledge, this is the first
      report suggesting an association between oral EDTA and oxalate nephropathy.

PMID- 28739330
TI  - Erratum Regarding "Kidney Injury and Repair Biomarkers in Marathon Runners" (Am J
      Kidney Dis. 2017;70[2]:252-261).

PMID- 28739329
TI  - Peptide Receptor Radionuclide Therapy-Induced Gitelman-like Syndrome.
AB  - Peptide receptor radionuclide therapy (PRRT) is a molecular-targeted therapy in
      which a somatostatin analogue (a small peptide) is coupled with a radioligand so
      that the radiation dose is selectively administered to somatostatin receptor
      expressing metastasized neuroendocrine tumors, particularly
      gastroenteropancreatic. Reported toxicities include myelotoxicity and
      nephrotoxicity, the latter manifesting as decreased kidney function, often
      developing months to years after treatment completion. We present a case of PRRT
      induced kidney toxicity manifesting as a severe Gitelman-like tubulopathy with
      preserved kidney function. Because profound hypokalemia and hypocalcemia can lead
      to life-threatening arrhythmias, we highlight the necessity for careful
      monitoring of serum and urine electrolytes in patients receiving PRRT.

PMID- 28739331
TI  - Associations of Sex Hormones and Anthropometry with the Speaking Voice Profile in
      the Adult General Population.
AB  - OBJECTIVE: There is evidence that sexual hormone concentrations and
      anthropometric factors influence the human voice. The goal of this study was to
      investigate to what extent body mass index (BMI), body height, body weight,
      breast-to-abdomen-ratio, testosterone, estradiol, dehydroepiandrosterone-sulfate
      (DHEA-S), follicle-stimulating hormone, and luteinizing hormone are associated
      with the sound pressure level and the fundamental frequency of the speaking voice
      in a cross-sectional approach among adults in the general population. METHODS:
      Speaking voice profiles with four different intensity levels, hormone
      concentrations, and anthropometric parameters were assessed for 2,381 individuals
      aged 40-79 years, who were randomly sampled from the population of a large city
      in Germany. Multivariate analysis was performed, adjusting for age and stratified
      by sex. RESULTS: Taller body height was associated with lower frequencies. Higher
      body weight was associated with lower frequencies and higher sound pressure
      levels. The ratio of chest to abdominal circumference was associated with the
      sound pressure levels in males and females: participants with larger breast-to
      abdomen-ratio were found to have higher sound pressure levels. Among the sexual
      hormones, higher concentrations of DHEA-S were associated with lower fundamental
      frequencies of the voice while using the normal speaking voice. In addition,
      bioavailable testosterone was associated with the sound pressure level of the
      normal speaking voice in men and the softest speaking voice in women. CONCLUSION:
      Our findings suggest that BMI, body height, body weight, breast-to-abdomen-ratio,
      bioavailable testosterone, and DHEA-S are associated with the speaking voice in
      adults. No associations between testosterone and the frequency of the speaking
      voice were found.

PMID- 28739332
TI  - Effects of Voice Therapy on Muscle Tension Dysphonia: A Systematic Literature
      Review.
AB  - The present study aimed to carry out a systematic review of the effects of voice
      therapy on individuals diagnosed with muscle tension dysphonia (MTD) or
      hyperfunctional dysphonia. This is a systematic literature review on the
      databases Medline (via PubMed), Cochrane Library, Scopus, and Lilacs using a
      search strategy related to the theme of the study. The selection included
      clinical trials that assessed the effects of speech therapy intervention on
      patients diagnosed with MTD or hyperfunctional dysphonia published over the last
      10 years in Portuguese, English, or Spanish. The Physiotherapy Evidence-Based
      Database (PEDro) Scale was used to assess the methodology of the studies. Of the
      634 publications, 12 studies were included in this review, of which three were
      excluded due to a low score on the PEDro Scale, resulting in a final number of
      nine publications. Regarding the techniques approached, semioccluded vocal tract
      exercises (22.22%), nasal sound and frequency modulation (22.22%), maximum
      phonation time (MPT) technique and vocal hygiene (11.11%), vocal function
      exercises (11.11%), respiratory exercises along with phonoarticulatory sounds
      (11.11%), manual laryngeal therapy (11.11%), and manual laryngeal therapy
      associated with respiratory exercises (11.11%) were identified. These techniques
      promoted the following effects: improvement in intraoral and subglottal pressure,
      positive alterations in the glottal contact quotient, significant changes in
      fundamental frequency measures, increased MPT, and reduced voice roughness.
      Methodology was identified to be a shortcoming in the studies. The clinical
      trials reviewed showed positive results in using the therapeutic techniques
      selected in the speech therapy approach.

PMID- 28739333
TI  - Comparison of Two Multiparameter Acoustic Indices of Dysphonia Severity: The
      Acoustic Voice Quality Index and Cepstral Spectral Index of Dysphonia.
AB  - OBJECTIVES: The Acoustic Voice Quality Index (AVQI) and the Cepstral Spectral
      Index of Dysphonia (CSID) are two multiparameter acoustic indices designed to
      objectively estimate dysphonia severity and track treatment outcomes. This study
      compared the performance of these two indices using a common corpus of dysphonic
      speakers. METHOD: Pre- and posttreatment samples of sustained vowel and connected
      speech were elicited from 112 patients across six diagnostic categories:
      unilateral vocal fold paralysis (n = 20), adductor spasmodic dysphonia (n = 20),
      primary muscle tension dysphonia (n = 20), benign vocal fold lesions (n = 20),
      presbylaryngis (n = 20), and mutational falsetto (n = 12). Listener ratings of
      dysphonia severity were compared to acoustic estimates of severity derived from
      two iterations of the AVQI (versions 2.02 and 3.01) as well as the CSID. RESULTS:
      The AVQI- and CSID-estimated severity for sustained vowels, connected speech, and
      a combined context were strongly correlated and significantly associated with
      listener ratings pretreatment, posttreatment, and change observed pre- to
      posttreatment. However, multiple regression analysis (adjusted for age, sex, and
      diagnostic category) revealed that the CSID generally accounted for more variance
      in listener-perceived severity ratings, and the contribution of the AVQI was
      small and statistically insignificant when the CSID was already in a combined
      model. CONCLUSIONS: The AVQI and the CSID were strongly correlated and both
      provided valid estimates of dysphonia severity. However, associations observed
      between the CSID- and listener-estimated dysphonia were almost uniformly stronger
      than either version of the AVQI, suggesting that the CSID outperformed the AVQI.

PMID- 28739334
TI  - Oocyte spindle transfer for prevention of mitochodrial disease: the question of
      membrane fusion technique.

PMID- 28739335
TI  - Weight decrease improves live birth rates in obese women undergoing IVF: a pilot
      study.
AB  - Obese women have lower pregnancy rates than normal-weight women undergoing
      assisted reproductive treatment. We conducted a pilot study to evaluate whether a
      12-week diet and exercise intervention before an IVF cycle would influence
      pregnancy rates in obese women. Forty-one patients were enrolled in this study.
      They were randomly allocated to two groups: an intervention group (n = 21), who
      underwent an individualized diet and physical exercise programme supervised by a
      dietician, and a control group (n = 20), who started IVF with no previous
      intervention. The primary outcome was clinical pregnancy rate after a single
      treatment cycle. Mean weight loss in the study group after the intervention was
      5.4 kg (range 1.1-14.6 kg). The study and control groups had similar total FSH
      consumption, number of oocytes and embryos obtained, and number and quality of
      embryos transferred. There was a non-significant trend towards a higher clinical
      pregnancy rate after fresh embryo transfer (66.7% versus 41.2%). The intervention
      group had a significantly higher cumulative live birth rate (61.9% versus 30%, P
      = 0.045) (odds ratio for intervention group, 3.8; 95% confidence interval, 1.03
      to 13.9) The data suggest that weight loss resulted in a significantly increased
      cumulative live birth rate.

PMID- 28739336
TI  - Oral tolerance and allergy.
AB  - Food allergy prevalence is increasing in the developed world. It's estimated that
      each year in the US, anaphylaxis to food results in 30,000 emergency room visits
      and 150 deaths. Over the past few decades, there has been a tremendous effort to
      better understand the pathogenesis of food allergy and mechanisms of food
      tolerance. In this article we review the structural of the gastrointestinal
      immune system and mechanisms of natural tolerance to food. We then review the
      factors that may result in the IgE mediated hypersensitivity reaction to food
      allergens resulting in clinical food allergy. Lastly, we provide a brief review
      of the efforts to induce immune tolerance to patients with food allergy.

PMID- 28739337
TI  - Evaluation of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry for identification of human oral Capnocytophaga species.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) was evaluated for rapid identification of cfxA PCR positive and
      negative Capnocytophaga strains. Colonies were grown on blood agar, incubated
      anaerobically at 37  degrees C for 48 h, and were then evaluated by MALDI-TOF MS
      and 16S rRNA gene sequencing. Both methods identified all colonies to the genus
      level. The MALDI-TOF MS method gave the same result, at the species level, as 16S
      rRNA gene sequencing for 41/53 Capnocytophaga sp. strains (77.4%), but the limit
      of this technique was the absence of some species (C. leadbetteri, C. AHN) in the
      Biotyper-Bruker(r) database used in this study. Distinction between the
      cefotaxime resistant and susceptible strains was unsuccessful using the MALDI-TOF
      MS method. This technique had low discriminatory power to rapidly detect beta
      lactamase-producing Capnocytophaga strains in clinical samples. However, the
      results from a score-oriented dendrogram confirmed MALDI-TOF MS is a rapid,
      inexpensive, and reliable method for Capnocytophaga species identification.
      Enrichment of the reference database used (Biotyper(r)) will improve future
      results.

PMID- 28739338
TI  - Comparative phenotypic analysis of "Clostridium neonatale" and Clostridium
      butyricum isolates from neonates.
AB  - "Clostridium neonatale" was recently described as a new species within the
      Cluster I of the Clostridium genus sensu stricto. In this study, we characterized
      "C. neonatale" isolates (n = 42) and compared their phenotypic properties with
      those of Clostridium butyricum (n = 26), a close related species. Strains
      isolated from fecal samples of healthy neonates were tested for different
      phenotypic characteristics. Compared to C. butyricum, "C. neonatale" showed a
      significant higher surface hydrophobicity (p = 0.0047), exopolysaccharide
      production (p = 0.0069), aero-tolerance (p = 0.0222) and viability at 30  degrees
      C (p = 0.0006). A lower swimming ability (p = 0.0146) and tolerance against bile
      (0.3%) (p = 0.0494), acid (pH 4.5) (p < 0.0001), osmolarity (NaCl 5%, p = 0.0188)
      and temperature at 50  degrees C (p = 0.0013) characterized "C. neonatale"
      strains. Our results showed that "C. neonatale" behaves very differently from C.
      butyricum and suggests specific responses to environmental changes. Besides it is
      the first study on clinical isolates for these two anaerobic members of the
      newborns' gut microbiota and broadens our knowledge about their phenotypic
      traits.

PMID- 28739339
TI  - Challenges in defining the role of intron retention in normal biology and
      disease.
AB  - RNA sequencing has revealed a striking diversity in transcriptomic complexity, to
      which alternative splicing is a major contributor. Intron retention (IR) is a
      conserved form of alternative splicing that was originally overlooked in normal
      mammalian physiology and development, due mostly to difficulties in its
      detection. IR has recently been revealed as an independent mechanism of
      controlling and enhancing the complexity of gene expression. IR facilitates rapid
      responses to biological stimuli, is involved in disease pathogenesis, and can
      generate novel protein isoforms. Many challenges, however, remain in detecting
      and quantifying retained introns and in determining their effects on cellular
      phenotype. In this review, we provide an overview of these challenges, and
      highlight approaches that can be used to address them.

PMID- 28739340
TI  - Regulation of cell polarity by cell adhesion receptors.
AB  - The ability of cells to polarize is an intrinsic property of almost all cells and
      is required for the devlopment of most multicellular organisms. To develop cell
      polarity, cells integrate various signals derived from intrinsic as well as
      extrinsic sources. In the recent years, cell-cell adhesion receptors have turned
      out as important regulators of cellular polarization. By interacting with
      conserved cell polarity proteins, they regulate the recruitment of polarity
      complexes to specific sites of cell-cell adhesion. By initiating intracellular
      signaling cascades at those sites, they trigger their specific subcellular
      activation. Not surprisingly, cell-cell adhesion receptors regulate diverse
      aspects of cell polarity, including apico-basal polarity in epithelial and
      endothelial cells, front-to-rear polarity in collectively migrating cells, and
      planar cell polarity during organ development. Here, we review the recent
      developments highlighting the central roles of cell-cell adhesion molecules in
      the development of cell polarity.

PMID- 28739341
TI  - Atomic force microscope as a nano- and micrometer scale biological manipulator: A
      short review.
AB  - The amazing capacity of atomic force microscope to let us touch the molecular and
      cellular level samples with a sharp probe stimulated its application to bio
      medical field among others. In addition to topographical imaging of the sample
      surface, a direct mechanical manipulation has attracted innovative minds to
      develop new methodologies aiming at direct handling of proteins, DNA/RNA, and
      cells. Measurement of their mechanical properties brought about a vivid picture
      of their physical nature. Direct handling of individual molecules and cells
      prompted development of nano-medical applications. This short review summarized
      recent application of AFM for measurement of mechanical properties of biological
      samples and attempts to perform direct manipulations of nano-medicine.

PMID- 28739342
TI  - A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment
      Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age
      Related Macular Degeneration.
AB  - Current treatments for choroidal neovascularization, a major cause of blindness
      for patients with age-related macular degeneration, treat symptoms but not the
      underlying causes of the disease. Inflammation has been strongly implicated in
      the pathogenesis of choroidal neovascularization. We examined the inflammatory
      role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was
      robustly expressed by the retinal pigment epithelium in mouse and human eyes,
      both normal and with macular degeneration/choroidal neovascularization. Nuclear
      localization of NF-kappaB, a major downstream target of TLR2 signaling, was
      detected in the retinal pigment epithelium of human eyes, particularly in eyes
      with advanced stages of age-related macular degeneration. TLR2 antagonism
      effectively suppressed initiation and growth of spontaneous choroidal
      neovascularization in a mouse model, and the combination of anti-TLR2 and
      antivascular endothelial growth factor receptor 2 yielded an additive therapeutic
      effect on both area and number of spontaneous choroidal neovascularization
      lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand
      binding to TLR2 induced robust expression of proinflammatory cytokines, and end
      products of lipid oxidation had a synergistic effect on TLR2 activation. Our data
      illustrate a functional role for TLR2 in the pathogenesis of choroidal
      neovascularization, likely by promoting inflammation of the retinal pigment
      epithelium, and validate TLR2 as a novel therapeutic target for reducing
      choroidal neovascularization.

PMID- 28739343
TI  - Inhibition of Cell Apoptosis and Amelioration of Pulmonary Fibrosis by
      Thrombomodulin.
AB  - Pulmonary fibrosis is the terminal stage of a group of idiopathic interstitial
      pneumonias, of which idiopathic pulmonary fibrosis is the most frequent and fatal
      form. Recent studies have shown that recombinant human thrombomodulin (rhTM)
      improves exacerbation and clinical outcome of idiopathic pulmonary fibrosis, but
      the mechanism remains unknown. This study evaluated the mechanistic pathways of
      the inhibitory activity of rhTM in pulmonary fibrosis. Transgenic mice
      overexpressing human transforming growth factor-beta1 that develop spontaneously
      pulmonary fibrosis, and wild-type mice treated with bleomycin were used as models
      of lung fibrosis. rhTM was administered to mice by i.p. injection or by the
      intranasal route. Therapy with rhTM significantly decreased the concentration of
      high mobility group box1, interferon-gamma, and fibrinolytic markers, the
      expression of growth factors including transforming growth factor-beta1, and the
      degree of lung fibrosis. rhTM significantly suppressed apoptosis of lung
      epithelial cells in in vivo and in vitro experiments. The results of the present
      study demonstrated that rhTM can inhibit bleomycin-induced pulmonary fibrosis and
      transforming growth factor-beta1-driven exacerbation and progression of pulmonary
      fibrosis, and that apart from its well-recognized anticoagulant and anti
      inflammatory properties, rhTM can also suppress apoptosis of lung epithelial
      cells.

PMID- 28739345
TI  - Urine-Specific Gravity-Based Hydration Prevents Stroke in Evolution in Patients
      with Acute Ischemic Stroke.
AB  - BACKGROUND: Early neurological deterioration after ischemic stroke (stroke-in
      evolution [SIE]) is associated with poorer outcomes. Previous studies have
      demonstrated a link between hydration status and the development of SIE. In this
      study, we tested the hypothesis that rehydration therapy, administered on the
      basis of urine-specific gravity (USG) findings, might reduce the development of
      SIE. METHODS: We conducted a single-arm prospective study of patients with acute
      ischemic stroke with historical controls. For the study group, a USG higher than
      1.010 was taken as an indication for rehydration. Control group patients were
      rehydrated without referring to USG. An increase in National Institutes of Health
      Stroke Scale (NIHSS) score of 4 or higher within 3 days was defined as having
      SIE. RESULTS: A total of 445 patients were analyzed, 167 in the study group and
      278 in the control group. The proportion of patients who developed SIE was
      numerically, but not significantly, lower in the study group (5.9%; 10 of 167)
      compared with the control group (11.5%; 32 of 278). Among patients with a USG
      higher than 1.010 at admission, the SIE rate was significantly reduced in the
      study group compared with the control group (6.1% versus 16.0%; P = .021), while
      the rate of SIE was similar in those with a USG of 1.010 or lower at admission.
      Multivariate logistic regression analysis confirmed that USG-based hydration was
      an independent factor associated with reducing SIE. CONCLUSIONS: USG might be a
      convenient and useful method for guiding fluid therapy in patients with acute
      ischemic stroke. USG-based hydration reduced the incidence of SIE among patients
      with a USG higher than 1.010 at admission.

PMID- 28739344
TI  - Design and Rationale of the Intima-Medial Thickness Sub-Study of the PreventIon
      of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral
      hemOrrhage (PICASSO-IMT) Study.
AB  - BACKGROUND: Atherosclerosis is one of the main mechanisms of stroke and
      cardiovascular diseases and is associated with increased risk of recurrent stroke
      and cardiovascular events. Intima-medial thickness (IMT) is a well-known
      surrogate marker of atherosclerosis and has been used to predict stroke and
      cardiovascular events. However, the clinical significance of IMT and IMT change
      in stroke has not been investigated in well-designed studies. The PreventIon of
      CArdiovascular events in iSchemic Stroke patients with high risk of cerebral
      hemOrrhage-Intima-Media Thickness (PICASSO-IMT) sub-study is designed to
      investigate the effects of cilostazol, probucol, or both on IMT in patients with
      stroke. METHODS: PICASSO-IMT is a prospective sub-study of the PICASSO study
      designed to measure IMT and plaque score at 1, 13, 25, 37, and 49 months after
      randomization. RESULTS: The primary outcome is the change in mean carotid IMT,
      which is defined as the mean of the far-wall IMTs of the right and left common
      carotid arteries, between baseline and 13 months after randomization. CONCLUSION:
      PICASSO-IMT will provide the largest IMT data set in a stroke population and will
      provide valuable information about the clinical significance of IMT in patients
      with ischemic stroke.

PMID- 28739346
TI  - A Method of Calculating Functional Independence Measure at Discharge from
      Functional Independence Measure Effectiveness Predicted by Multiple Regression
      Analysis Has a High Degree of Predictive Accuracy.
AB  - BACKGROUND: Multiple linear regression analysis is often used to predict the
      outcome of stroke rehabilitation. However, the predictive accuracy may not be
      satisfactory. The objective of this study was to elucidate the predictive
      accuracy of a method of calculating motor Functional Independence Measure (mFIM)
      at discharge from mFIM effectiveness predicted by multiple regression analysis.
      METHODS: The subjects were 505 patients with stroke who were hospitalized in a
      convalescent rehabilitation hospital. The formula "mFIM at discharge = mFIM
      effectiveness * (91 points - mFIM at admission) + mFIM at admission" was used. By
      including the predicted mFIM effectiveness obtained through multiple regression
      analysis in this formula, we obtained the predicted mFIM at discharge (A). We
      also used multiple regression analysis to directly predict mFIM at discharge (B).
      The correlation between the predicted and the measured values of mFIM at
      discharge was compared between A and B. RESULT: The correlation coefficients were
      .916 for A and .878 for B. CONCLUSION: Calculating mFIM at discharge from mFIM
      effectiveness predicted by multiple regression analysis had a higher degree of
      predictive accuracy of mFIM at discharge than that directly predicted.

PMID- 28739347
TI  - Association of Vitamin D Receptor Gene Polymorphism in Adults With Type 2
      Diabetes in the Kashmir Valley.
AB  - OBJECTIVES: Approx 1 billion people across various ethnic and age groups have
      vitamin D deficiency. The high prevalence of such a deficiency is an imperative
      public health issue because hypovitaminosis D is an autonomous risk factor for
      mortality in the general population. Beyond bone integrity and calcium
      homeostasis, it is involved in numerous physiologic and pathologic processes. The
      role of vitamin D in the pathogenesis and prevention of type 2 diabetes mellitus
      has sparked universal interest. METHODS: This hospital-based case-control study
      was designed to study the association between 25-hydroxy vitamin D (25[OH]D)
      levels and the vitamin D receptor (VDR) gene polymorphism with diabetes and to
      evaluate their roles as risk factors for diabetes. 100 cases and controls were
      taken. 25(OH)D levels were analyzed by the chemilumenescence method using a
      Siemens ADVIA Centaur analyzer. Genomic DNA was extracted and Taq-1 and Bsm-1
      genotyping in the VDR gene was done by using the polymerase chain reaction
      followed by restriction fragment length polymorphism (PCR-RFLP). RESULTS: 25(OH)D
      levels of patients with diabetes were significantly lower than those of controls
      (19.26+/-0.95 ng/mL vs. 25.49+/-1.02 ng/mL; p=0.001). 25(OH)D levels were found
      to be inversely associated with glycated hemoglobin percentages in cases
      (r2=0.74). The results suggested that the single nucleotide polymorphisms Taq-1
      t(T) allele and b (G allele) in Bsm-1 might be a susceptibility allele for
      diabetes in the Kashmiri population. CONCLUSIONS: VDR gene polymorphisms appear
      to be an important genetic determinant in the progression of diabetes.
      Considering the important predisposition risk factor, we observed that Taq-1 and
      Bsm-1 were strongly associated with diabetes in northern Indians. But requires
      further study as a probable genetic risk marker for diabetes.

PMID- 28739348
TI  - Senescence-accelerated mouse prone 8 (SAMP8) as a model of age-related hearing
      loss.
AB  - Hearing loss is the most common form of sensory impairment in humans, affecting
      5.3% worldwide population. In industrial countries, age-related hearing loss is a
      major health problem affecting one-third of individuals over 65years old.
      However, the physiological and molecular changes involved in this senescence
      process remain unclear. In this study, we determined the influence of age on
      auditory brainstem response (ABR) and the distortion product otoacoustic
      emissions (DPOAE) in the premature senescence mouse model SAMP8 for five months.
      We showed a progressive increase of ABR thresholds and a decrease of distortion
      product amplitude from 37days old in SAMP8 compared to CBA mice. The data we show
      here provide new knowledge in functional auditory changes during the senescence
      process and open up new opportunities for the development of new drugs involved
      in age-related hearing loss treatment.

PMID- 28739349
TI  - Autophagy protects against PI3K/Akt/mTOR-mediated apoptosis of spinal cord
      neurons after mechanical injury.
AB  - Many studies have indicated that autophagy and apoptosis play an important role
      in the pathogenesis of spinal cord injury. In recent years, research on autophagy
      related signal transduction pathways has demonstrated that the
      phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of
      rapamycin (mTOR) signaling pathway is closely associated with the initiation of
      autophagy. However, the mechanism of the pathological relationship between this
      signaling pathway and apoptosis in spinal cord injury is unclear. In this study,
      we used an in vitro model of spinal cord injury to observe the mechanism of the
      PI3K/Akt/mTOR signaling pathway and the apoptosis of neurons via the
      mitochondrial pathway. Mitochondrial pathway apoptosis-related proteins were
      detected by western blot. Akt and mTOR phosphorylation levels peaked 4h after
      mechanical damage and then decreased. Following administration of the PI3K
      specific inhibitor LY294002, the phosphorylation levels of Akt and mTOR
      decreased, and the ratio of autophagy-specific protein microtubule-associated
      protein 1 light chain (LC3)II/I was higher in the inhibitor-treated injury group
      than in the simple-injury group. TUNEL staining was used to detect apoptosis, and
      apoptosis was significantly reduced after the inhibition of the PI3K/Akt/mTOR
      signaling pathway. In summary, the PI3K/Akt/mTOR signaling pathway is involved in
      the apoptosis of neurons after mechanical injury and can induce apoptosis through
      the mitochondrial pathway.

PMID- 28739350
TI  - Uric acid level as predictor of mortality in the acute care setting of advanced
      age population.

PMID- 28739351
TI  - Unnecessary hospitalizations for DVT in the era of NOACs.

PMID- 28739352
TI  - Should a scientist be prevented from publishing in a journal for which he works?

PMID- 28739353
TI  - Incidence of tuberculosis among patients with rheumatoid arthritis using TNF
      blockers in Brazil: data from the Brazilian Registry of Biological Therapies in
      Rheumatic Diseases (Registro Brasileiro de Monitoracao de Terapias Biologicas -
      BiobadaBrasil).
AB  - OBJECTIVES: To assess the incidence of tuberculosis and to screen for latent
      tuberculosis infection among Brazilians with rheumatoid arthritis using biologics
      in clinical practice. PATIENTS AND METHODS: This cohort study used data from the
      Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro
      Brasileiro de Monitoracao de Terapias Biologicas - BiobadaBrasil), from 01/2009
      to 05/2013, encompassing 1552 treatments, including 415 with only synthetic
      disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti
      tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic
      DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The
      occurrence of tuberculosis and the drug exposure time were assessed, and
      screening for tuberculosis was performed. STATISTICAL ANALYSIS: Unpaired t-test
      and Fisher's two-tailed test; p<0.05. RESULTS: The exposure times were 981
      patient-years in the controls, 1744 patient-years in the anti-TNF group
      (adalimumab=676, infliximab=547 and etanercept=521 patient-years) and 336 patient
      years in the other biologics group. The incidence rates of tuberculosis were
      1.01/1000 patient-years in the controls and 2.87 patient-years among anti-TNF
      users (adalimumab=4.43/1000 patient-years; etanercept=1.92/1000 patient-years and
      infliximab=1.82/1000 patient-years). No cases of tuberculosis occurred in the
      other biologics group. The mean drug exposure time until the occurrence of
      tuberculosis was 27(11) months for the anti-TNF group. CONCLUSIONS: The incidence
      of tuberculosis was higher among users of synthetic DMARDs and anti-TNF than
      among users of synthetic DMARDs and synthetic DMARDs and non-anti-TNF biologics
      and also occurred later, suggesting infection during treatment and no screening
      failure.

PMID- 28739354
TI  - Recommendations of the Brazilian Society of Rheumatology for the diagnosis and
      treatment of chikungunya fever. Part 2 - Treatment.
AB  - Chikungunya fever has become an important public health problem in countries
      where epidemics occur because half of the cases progress to chronic, persistent
      and debilitating arthritis. Literature data on specific therapies at the various
      phases of arthropathy caused by chikungunya virus (CHIKV) infection are limited,
      lacking quality randomized trials assessing the efficacies of different
      therapies. There are a few studies on the treatment of musculoskeletal
      manifestations of chikungunya fever, but these studies have important
      methodological limitations. The data currently available preclude conclusions
      favorable or contrary to specific therapies, or an adequate comparison between
      the different drugs used. The objective of this study was to develop
      recommendations for the treatment of chikungunya fever in Brazil. A literature
      review was performed via evidence-based selection of articles in the databases
      Medline, SciELO, PubMed and Embase and conference proceedings abstracts, in
      addition to expert opinions to support decision-making in defining
      recommendations. The Delphi method was used to define the degrees of agreement in
      2 face-to-face meetings and several online voting rounds. This study is part 2 of
      the Recommendations of the Brazilian Society of Rheumatology (Sociedade
      Brasileira de Reumatologia - SBR) for the Diagnosis and Treatment of chikungunya
      fever and specifically addresses treatment.

PMID- 28739355
TI  - 3-D computed tomography measurement of mandibular growth after costochondral
      grafting in growing children with temporomandibular joint ankylosis and jaw
      deformity.
AB  - OBJECTIVE: The aim of this study was to evaluate the long-term results after
      costochondral grafting (CCG) in growing children with temporomandibular joint
      ankylosis and jaw deformity by 3-dimensional computed tomography (CT)
      measurement. STUDY DESIGN: Patients with unilateral TMJ ankylosis and jaw
      deformity treated by CCG from 2010 to 2014 were evaluated. Their CT data within 1
      week after operation and after at least 2 years of follow-up were analyzed using
      ProPlan CMF 1.4 software. Maximal incisal opening (MIO), condyle-ramus heights,
      chin deviation, and growth of CCG were measured and compared before and after the
      operation and at the last follow-up. SPSS 17.0 software was used for statistical
      analysis. RESULTS: Seven patients were included in the study. The mean follow-up
      period was 46.4 months. Five of 7 patients treated with this protocol experienced
      good mouth opening and symmetric mandibular growth. One patient achieved good
      mouth opening but not symmetric growth, and 1 patient experienced ankylosis
      again. CONCLUSIONS: CCG can be a reliable method to treat temporomandibular joint
      ankylosis with jaw deformity in growing children. Continued growth occurs in the
      children, but long-term outcomes require further investigation.

PMID- 28739356
TI  - Development of autoantibodies precedes clinical manifestations of autoimmune
      diseases: A comprehensive review.
AB  - The etiology of autoimmune diseases is due to a combination of genetic
      predisposition and environmental factors that alter the expression of immune
      regulatory genes through various mechanisms including epigenetics. Both humoral
      and cellular elements of the adaptive immune system play a role in the
      pathogenesis of autoimmune diseases and the presence of autoantibodies have been
      detected in most but not all autoimmune diseases before the appearance of
      clinical symptoms. In some cases, the presence or levels of these autoantibodies
      portends not only the risk of developing a corresponding autoimmune disease, but
      occasionally the severity as well. This observation is intriguing because it
      suggests that we can, to some degree, predict who may or may not develop
      autoimmune diseases. However, the role of autoantibodies in the pathogenesis of
      autoimmune diseases, whether they actually affect disease progression or are
      merely an epiphenomenon is still not completely clear in many autoimmune
      diseases. Because of these gaps in our knowledge, the ability to accurately
      predict a future autoimmune disease can only be considered a relative risk
      factor. Importantly, it raises the critical question of defining other events
      that may drive a patient from a preclinical to a clinical phase of disease.

PMID- 28739357
TI  - Attracting men to nursing: Is graduate entry an answer?
AB  - There is evidence which suggests that second degree graduate entry nursing
      programs may be a potential strategy to increase the number of men in nursing.
      This qualitative study used thematic analysis to describe the reasons
      underpinning men's enrolment in the first three intakes of the first such program
      in New Zealand. Interrogation of the data revealed two primary themes. First, in
      search of a satisfying career with the associated subthemes: was at a loss;
      fulfilment through working with and helping people; and a career with options.
      The second theme the time was right was underpinned by two subthemes: The right
      time of life; and, the right course. In contrast, to previous studies of men in
      nursing it was found that vertical career progression into management was not
      attractive, and that career satisfaction was seen as being able to help others.
      The findings may provide insight for developing strategies which encourage men's
      entry into nursing.

PMID- 28739360
TI  - Type III Spinal Cord Arteriovenous Malformation With Good Postsurgical Outcome.

PMID- 28739359
TI  - Prevalence of Sleep Abnormalities in Indian Children With Autism Spectrum
      Disorder: A Cross-Sectional Study.
AB  - BACKGROUND: The prevalence of autism spectrum disorder (ASD) is on the rise.
      Apart from the core behavioral issues of impaired communication, impaired social
      interaction, and restricted and/or repeated behavioral phenotype, comorbidities
      like sleep problems are increasingly getting recognized as important determinants
      of management and overall quality of life. METHODS: This study was conducted in a
      tertiary care teaching hospital in northern India over a two year period.
      Children diagnosed with ASD and normally developing children (control subjects)
      aged 3 to 10 years were enrolled in the study. Both groups underwent sleep
      evaluation based on the Children's Sleep Habit Questionnaire. Children with ASD
      also underwent polysomnography, Childhood Autism Rating Scale, Childhood
      Behavioral Checklist, and Developmental Profile 3 assessments. RESULTS: The
      prevalence of poor sleepers among children with ASD and control subjects was
      77.5% (confidence interval 66 to 86.5). and 29.2% (confidence interval 18.6 to
      41.5), respectively (P < 0.001). The salient findings on polysomnography were
      reduced sleep efficiency, decreased rapid eye movement and slow wave sleep
      duration, and desaturation index>1. The Childhood Behavioral Checklist score was
      significantly high in poor sleepers compared with good sleepers on Children's
      Sleep Habit Questionnaire (P = 0.004). There was no correlation of Childhood
      Autism Rating Scale or Developmental Profile 3 score with sleep problems in
      children with ASD. CONCLUSIONS: Nearly three fourths of children with ASD have
      sleep abnormalities with a possible effect on the behavioral phenotype. The
      polysomnographic findings provide further insight with opportunity for
      pharmacological interventions. Screening for sleep problems is imperative for the
      appropriate management and overall improvement in quality of life in children
      with ASD.

PMID- 28739361
TI  - Gender Affects Long-Term Neurological Outcome of Neonates.
AB  - OBJECTIVE: We evaluated the possible association between fetal gender and long
      term pediatric neurological morbidity. METHODS: We performed a population-based
      retrospective cohort analysis comparing the risk of long-term neurological
      morbidity (up to age 18 years) of children born during the years 1991 to 2013
      according to their gender. Neurological morbidity evaluated included
      hospitalizations in childhood involving pervasive developmental disorder,
      obstructive sleep apnea, cerebral palsy, epilepsy, and infantile spasms and
      disorders of eating as recorded in the hospital files. Multiple pregnancies and
      fetal congenital malformations were excluded. Kaplan-Meier survival curves were
      constructed to compare the cumulative neurological morbidity over the study
      period. A Cox proportional hazards model was used to control for obstetrical
      confounders, including gestational age at birth, birth weight, and maternal
      factors. RESULTS: During the study period, 240,953 newborns were included in the
      long-term analysis: 51.0% (n = 122,840) males and 49.0% (n = 118,113) females.
      Hospitalizations for neurological problems (up to age 18 years) were
      significantly more common in males compared with females (1.1% vs 0.8%,
      respectively, odds ratio 1.31, 95% confidence interval 1.2 to 1.4, P < 0.001).
      Specifically, pervasive developmental disorder and obstructive sleep apnea were
      found to be significantly more common in males, and cerebral palsy reached
      borderline significance (0.1% vs 0.04%, odds ratio 1.39, 95% confidence interval
      0.9 to 1.9, P = 0.06). The Kaplan-Meier survival curves demonstrated males to
      have a significantly higher cumulative incidence of total neurological morbidity
      as well as of pervasive developmental disorder and obstructive sleep apnea (all
      log-rank test P values <0.001). In the Cox regression model, male gender
      exhibited an independent association with long-term neurological morbidity, while
      adjusting for birth weight, gestational age, and other confounding variables
      (adjusted hazard ratio 1.29, 95% confidence interval 1.2 to 1.4, P < 0.001).
      CONCLUSION: Males are at an increased risk for pediatric neurological morbidity
      independent of gestational age at birth and birth weight.

PMID- 28739362
TI  - Stroke in Ehlers-Danlos Syndrome Kyphoscoliotic Type: Dissection or Vasculitis?
AB  - BACKGROUND: Patients with the kyphoscoliotic type of Ehlers-Danlos syndrome have
      an increased risk of vascular complications such as aortic dissection and
      perforation. Cerebral ischemia has only rarely been documented. PATIENT
      DESCRIPTION: This 13-year-old girl with the kyphoscoliotic type of Ehlers-Danlos
      syndrome experienced a large right middle cerebral artery distribution
      infarction. Full intravenous heparinization was started in response to presumed
      arterial dissection. Magnetic resonance imaging studies including magnetic
      resonance angiography and digital subtraction angiography, however, did not
      confirm dissection but suggested with cerebral vasculitis extending from the
      intradural right internal carotid artery to the M2 branches of the middle
      cerebral artery. Combined steroid and cyclophosphamide therapy was associated
      with clinical improvement. Two months later she died from hemorrhagic shock
      caused by a two-sided spontaneous rupture of the aortic artery. CONCLUSIONS:
      Cerebral vasculitis should be included in the differential diagnosis of vascular
      complications in kyphoscoliotic type of Ehlers-Danlos syndrome.

PMID- 28739363
TI  - Involvement of Cerebellum in Leigh Syndrome: Case Report and Review of the
      Literature.
AB  - BACKGROUND: Leigh syndrome is an early-onset progressive neurodegenerative
      disorder typically involving lesions of the bilateral basal ganglia, thalami, and
      brainstem. Isolated involvement of the cerebellum is uncommon. PATIENT
      DESCRIPTION: We present a six-year-old boy with Leigh syndrome who presented with
      recurrent episodes of ataxia and dysarthria. He was diagnosed with Leigh syndrome
      at two years of age with bilateral basal ganglia lesions on brain magnetic
      resonance imaging (MRI). Genetic testing confirmed a diagnosis of Leigh syndrome
      secondary to a homoplasmic mitochondrial DNA mutation (m.9176T>C). He experienced
      regressive episodes (ages five and six years). Each regressive episode had a
      similar presentation with worsening of baseline ataxia and dysarthria. The first
      episode mimicked infectious cerebellitis, with elevated cerebral spinal fluid
      (CSF) protein and white blood cell count. No organisms were isolated from the
      CSF/blood during any of the regressive episodes. Brain MRI consistently showed
      cerebellar lesions, however cerebellar spectroscopy during the second episode
      found an elevated lactate peak, a decrease of the N-acetylaspartate peak, and
      elevation of the choline peak; consistent with an acute exacerbation of Leigh
      syndrome. CONCLUSIONS: Leigh syndrome can present primarily with involvement of
      the cerebellum, and it should be considered in the differential diagnosis for
      acute cerebellitis.

PMID- 28739364
TI  - Neurodevelopmental Outcome of Asymptomatic Hypoglycemia Compared With Symptomatic
      Hypoglycemia and Euglycemia in High-Risk Neonates.
AB  - AIMS: We assessed the neurodevelopmental outcome at one year of age of children
      with asymptomatic neonatal hypoglycemia and compared their outcome with that of
      symptomatic hypoglycemic and euglycemic neonates. METHOD: Seventy two
      hypoglycemic (plasma glucose less than 50 mg/dL) neonates, both symptomatic (n =
      27) and asymptomatic (n = 45), and 70 weight- and gestation-matched euglycemic
      neonates of gestational age greater than 32 weeks were enrolled during the first
      week of life then assessed for neurodevelopmental outcome at corrected age six
      and 12 months (n = 67 and 62 in hypoglycemia group and 63 and 54 in euglycemia
      group, with the rest lost to follow-up, and death = 1). RESULTS: At one year, 8%
      (five of 62, four in symptomatic and one in asymptomatic group) of hypoglycemic
      neonates developed cerebral palsy. Mean motor and mental development quotients
      were significantly lower at corrected ages six and 12 months in any hypoglycemia
      (P < 0.001) and if blood glucose was less than 40 mg/dL (P < 0.001) when compared
      with euglycemia. Symptomatic infants had lower motor development quotient (P =
      0.004 and 0.003) and mental development quotient (P = 0.001 and 0.001) at
      corrected ages six and 12 months than asymptomatic infants, and asymptomatic
      infants had lower motor development quotient (P <= 0.001 and 0.004) and mental
      development quotient (P = 0.001 and 0.004) than the euglycemic group at corrected
      ages six and 12 months, respectively. Blood glucose of less than 40 mg/dL had
      high sensitivity (83% for motor development quotient and 81% for mental
      development quotient) for development quotient scores of less than 85.
      CONCLUSION: Hypoglycemia, both symptomatic and asymptomatic, leads to adverse
      neurodevelopmental outcome when compared with euglycemia, although it was worse
      in the symptomatic group and at blood glucose less than 40 mg/dL.

PMID- 28739365
TI  - Designing Predictive Models for Beta-Lactam Allergy Using the Drug Allergy and
      Hypersensitivity Database.
AB  - BACKGROUND: Beta-lactam antibiotics represent the main cause of allergic
      reactions to drugs, inducing both immediate and nonimmediate allergies. The
      diagnosis is well established, usually based on skin tests and drug provocation
      tests, but cumbersome. OBJECTIVES: To design predictive models for the diagnosis
      of beta-lactam allergy, based on the clinical history of patients with suspicions
      of allergic reactions to beta-lactams. METHODS: The study included a
      retrospective phase, in which records of patients explored for a suspicion of
      beta-lactam allergy (in the Allergy Unit of the University Hospital of
      Montpellier between September 1996 and September 2012) were used to construct
      predictive models based on a logistic regression and decision tree method; a
      prospective phase, in which we performed an external validation of the chosen
      models in patients with suspicion of beta-lactam allergy recruited from 3 allergy
      centers (Montpellier, Nimes, Narbonne) between March and November 2013. Data
      related to clinical history and allergy evaluation results were retrieved and
      analyzed. RESULTS: The retrospective and prospective phases included 1991 and 200
      patients, respectively, with a different prevalence of confirmed beta-lactam
      allergy (23.6% vs 31%, P = .02). For the logistic regression method, performances
      of the models were similar in both samples: sensitivity was 51% (vs 60%),
      specificity 75% (vs 80%), positive predictive value 40% (vs 57%), and negative
      predictive value 83% (vs 82%). The decision tree method reached a sensitivity of
      29.5% (vs 43.5%), specificity of 96.4% (vs 94.9%), positive predictive value of
      71.6% (vs 79.4%), and negative predictive value of 81.6% (vs 81.3%). CONCLUSIONS:
      Two different independent methods using clinical history predictors were unable
      to accurately predict beta-lactam allergy and replace a conventional allergy
      evaluation for suspected beta-lactam allergy.

PMID- 28739366
TI  - Management of Mastocytosis in Pregnancy: A Review.
AB  - In this article, the authors present a case of pregnancy complicated by the need
      for management of indolent systemic mastocytosis. The diagnosis of mastocytosis
      is reviewed, as well as subtypes of mastocytosis and management options
      particularly in pregnancy. A table of pregnancy/lactaction categories for common
      medications used in mastocytosis is presented.

PMID- 28739367
TI  - A hyperendemic focus of Taenia solium transmission in the Banke District of
      Nepal.
AB  - Neurocysticercosis is a major cause of epilepsy in countries where Taenia solium
      is endemic and the parasite is a major cause of food-borne disease globally. Pigs
      are the natural intermediate host involved in transmission of the parasite. T.
      solium is known to be endemic in Nepal, however there is limited reliable data
      about the prevalence of the disease in Nepal. The aim of this study was to
      determine accurately the prevalence of porcine cysticercosis in slaughter age
      pigs in an area of Nepal where pigs are known to be free-roaming. Pigs were
      obtained from the Udaypur Village Development Committee (VDC) and Hirminiya &
      Betahani VDC of the Banke district in Nepal. One hundred and ten animals of
      slaughter age (approximately 8-16 months old) were purchased, slaughtered and the
      heart, liver, brain and half the body skeletal musculature were sliced using hand
      knives and the number and viability of T. solium cysts determined. Thirty two of
      the 110 animals were found to harbour T. solium cysticerci (29%), of which 30
      (27%) were found to have viable cysticerci (93% of the infected animals). This is
      one of the highest prevalences of porcine cysticercosis that has been reported to
      date from the results of necropsy on randomly selected animals. This study
      highlights a high rate of transmission of T. solium in the Banke District of
      Nepal. It encourages further investigation of human and porcine cysticercosis in
      Nepal, as well as implementation of efforts to reduce transmission of the
      parasite and the associated human disease.

PMID- 28739368
TI  - Andrographolide induces oxidative stress-dependent cell death in unicellular
      protozoan parasite Trypanosoma brucei.
AB  - African sleeping sickness is a parasitic disease in humans and livestock caused
      by Trypanosoma brucei throughout sub-Saharan Africa. Absence of appropriate
      vaccines and prevalence of drug resistance proclaim that a new way of therapeutic
      interventions is essential against African trypanosomiasis. In the present study,
      we have looked into the effect of andrographolide (andro), a diterpenoid lactone
      from Andrographis paiculata on Trypanosoma brucei PRA 380. Although andro has
      been recognized as a promosing anti-cancer drug, its usefulness against
      Trypanosoma spp remained unexplored. Andro showed promising anti-trypanosomal
      activity with an IC50 value of 8.3MUM assessed through SYBR Green cell viability
      assay and also showed no cytotoxicity towards normal murine macrophages. Cell
      cycle analysis revealed that andro could induce sub-G0/G1 phase arrest. Flow
      cytometric analysis also revealed that incubation with andro caused exposure of
      phosphatidyl serine to the outer leaflet of plasma membrane in T. brucei PCF.
      This event was preceded by andro-induced depolarization of mitochondrial membrane
      potential (Deltaym) and elevation of cytosolic calcium. Andro also caused
      elevation of intracellular reactive oxygen species (ROS) as well as lipid
      peroxidation level, and depletion in reduced thiol levels. Taken together, these
      data indicate that andro has promising antitrypanosomal activity mediated by
      promoting oxidative stress and depolarizing the mitochondrial membrane potential
      and thereby triggering an apoptosis-like programmed cell death. Therefore, this
      study merits further investigation to the therapeutic possibility of using andro
      for the treatment of African trypanosomiasis.

PMID- 28739369
TI  - Genomic regression of claw keratin, taste receptor and light-associated genes
      provides insights into biology and evolutionary origins of snakes.
AB  - Regressive evolution of anatomical traits often corresponds with the regression
      of genomic loci underlying such characters. As such, studying patterns of gene
      loss can be instrumental in addressing questions of gene function, resolving
      conflicting results from anatomical studies, and understanding the evolutionary
      history of clades. The evolutionary origins of snakes involved the regression of
      a number of anatomical traits, including limbs, taste buds and the visual system,
      and by analyzing serpent genomes, I was able to test three hypotheses associated
      with the regression of these features. The first concerns two keratins that are
      putatively specific to claws. Both genes that encode these keratins are
      pseudogenized/deleted in snake genomes, providing additional evidence of claw
      specificity. The second hypothesis is that snakes lack taste buds, an issue
      complicated by conflicting results in the literature. I found evidence that
      different snakes have lost one or more taste receptors, but all snakes examined
      retained at least one gustatory channel. The final hypothesis addressed is that
      the earliest snakes were adapted to a dim light niche. I found evidence of
      deleted and pseudogenized genes with light-associated functions in snakes,
      demonstrating a pattern of gene loss similar to other dim light-adapted clades.
      Molecular dating estimates suggest that dim light adaptation preceded the loss of
      limbs, providing some bearing on interpretations of the ecological origins of
      snakes.

PMID- 28739370
TI  - Molecular systematics, species delimitation and diversification patterns of the
      Phyllodactylus lanei complex (Gekkota: Phyllodactylidae) in Mexico.
AB  - The description of cryptic gecko species worldwide has revealed both that many
      putative species are, in fact, conformed by a complex of morphologically
      conserved species that are genetically distinct and highly divergent, and that
      gecko species diversity could be underestimated. The taxonomy and species
      delimitation of geckos belonging to the genus Phyllodactylus is still
      controversial, 16 of which are distributed in Mexico and 13 are endemic. Although
      the large morphological variation shown by the Phyllodactylus species from Mexico
      has been amply documented, little is known about their genetic diversity and
      evolutionary relationships, and much less regarding cryptic speciation. Here, we
      included the most comprehensive sampling of populations and species of the
      Phyllodactylus lanei complex distributed in Mexico, and applied an analytical
      approach that included probabilistic phylogenetic analyses, jointly with species
      delimitation methods and Bayesian putative species validation analysis. Our
      results suggest the existence of 10 lineages within the complex, supporting the
      existence of cryptic species, and in great contrast with the current taxonomic
      proposal that includes only four subspecies. The most recent common ancestor
      (MRCA) for the P. lanei clade originated on the Early Eocene (~54Mya), along the
      southern coasts of Mexico, followed by the highest diversification of the complex
      MRCA during the Eocene (34-56Mya). Lineages subsequently dispersed and
      diversified towards the northwest, and the diversification process ended with the
      most recent lineages inhabiting two islands on the coasts of Nayarit (Miocene;
      5.5-23Mya). Our results highlight three vicariant events associated with the
      evolution of the lineages, two of them intimately related to the formation of the
      Sierra Madre del Sur and the Transmexican Volcanic Belt mountain ranges, main
      geographic barriers that isolated and facilitated the divergence and speciation
      in this group of geckos. Finally, we propose that there are 10 species in the P.
      lanei complex, from which four represent taxonomic changes and six are new
      species and require a formal description. We acknowledge that more analyses,
      including a detailed evaluation of morphological characters and use of more
      unlinked nuclear loci with enough variability, are needed to further support
      their taxonomic description.

PMID- 28739371
TI  - Trans-biome diversity in Australian grass-specialist lizards (Diplodactylidae:
      Strophurus).
AB  - Comparisons of biodiversity patterns within lineages that occur across major
      climate gradients and biomes, can provide insights into the relative roles that
      lineage history, landscape and climatic variation, and environmental change have
      played in shaping regional biotas. In Australia, while there has been extensive
      research into the origins and patterns of diversity in the Australian Arid Zone
      (AAZ), how diversity is distributed across this biome and the Australian
      Monsoonal Tropics (AMT) to the north, has been less studied. We compared the
      timing and patterns of diversification across this broad aridity gradient in a
      clade of lizards (Strophurus: phasmid geckos) that only occur in association with
      a unique Australian radiation of sclerophyllous grasses (Triodia: spinifex). Our
      results indicate that overall genetic diversity is much higher, older and more
      finely geographically structured within the AMT, including distantly related
      clades endemic to the sandstone escarpments of the Kimberley and Arnhem Plateau.
      Niche modelling analyses also suggest that the distribution of taxa in the AMT is
      more strongly correlated with variation in topographic relief than in the AAZ.
      The two broad patterns that we recovered - (i) lineage endemism increases as
      latitude decreases, and (ii) endemism is tightly correlated to rocky regions -
      parallel and corroborate other recent studies of habitat generalists and
      specialised saxicoline lineages occurring across these same regions. Early
      Miocene diversification estimates also suggest that, soon after Triodia grasses
      colonised Australia and began to diversify in the Miocene, phasmid geckos with
      Gondwanan ancestry shifted into these grasses, and have subsequently remained
      closely associated with this unique vegetation type.

PMID- 28739372
TI  - An improved and general streamlined phylogenetic protocol applied to the fatty
      acid desaturase family.
AB  - Numerous tools to generate phylogenetic estimates are available, but there is no
      single protocol that will produce an accurate phylogenetic tree for any dataset.
      Here, we investigated some of those tools, paying particular attention to
      different alignment algorithms, in order to produce a phylogeny for the integral
      membrane fatty acid desaturase (FAD) family. Herein, we report a novel
      streamlined protocol which utilises peptide pattern recognition (PPR). This
      protocol can theoretically be applied universally to generate accurate multiple
      sequence alignments and improve downstream phylogenetic analyses. Applied to the
      desaturases, the protocol generated the first detailed phylogenetic estimates for
      the family since 2003, which suggested they may have evolved from three
      functionally distinct desaturases and further, that desaturases evolved first in
      cyanobacteria. In addition to the phylogenetic outputs, we mapped PPR sequence
      motifs onto an X-ray protein structure to provide insights into biochemical
      function and demonstrate the complementarity of PPR and phylogenetics.

PMID- 28739373
TI  - Analyte variations in consecutive 24-hour urine collections in children.
AB  - PURPOSE: The metabolic evaluation of children with nephrolithiasis begins with a
      24-h urine collection. For adults, the diagnostic yield increases with
      consecutive collections; however, little is known regarding the variability of
      multiple 24-h studies in the pediatric population. We sought to evaluate the
      variability of consecutive 24-h urine collection in children through a multi
      institutional study hypothesizing that compared with a single collection,
      consecutive 24-h urine collections would reveal a greater degree of clinically
      useful information in the evaluation of children at risk for nephrolithiasis.
      MATERIALS AND METHODS: Including data from six institutions, we identified
      children less than 18 years of age considered at risk for recurrent
      nephrolithiasis, undergoing metabolic evaluation. We evaluated a subset of
      patients performing two collections with urine creatinine varying by 10% or less
      during a 7-day period. Discordance between repeat collections based on normative
      urine chemistry values was evaluated. RESULTS: A total of 733 children met
      inclusion criteria, and in over a third both urine calcium and urine volume
      differed by 30% or more between samples. Urine oxalate demonstrated greater
      variation between collections in children <5 years than among older children (p =
      0.030) while variation in other parameters did not differ by age. Discordance
      between repeat samples based on normative values was most common for urine
      oxalate (22.5%) and the derived relative supersaturation ratios for both calcium
      phosphate (25.1%) and calcium oxalate (20.5%). The proportion of discordant
      samples, based on normative thresholds, as well as variability greater >=30% and
      50%, respectively, are shown in the table. CONCLUSIONS: Our analysis indicates
      that stone risk in as many as one in four children may be misclassified if
      normative values of only a single 24-h urine are used. In light of these
      findings, repeat 24-h urine collections prior to targeted intervention to modify
      stone risk are advised to increase diagnostic yield in children at risk for
      nephrolithiasis.

PMID- 28739374
TI  - Re: Importance of neuropsychiatric evaluation in children with primary
      monosymptomatic enuresis.

PMID- 28739375
TI  - Oxidative stress and inhibition of nitric oxide generation underlie methotrexate
      induced senescence in human colon cancer cells.
AB  - The response of human colon cancer C85 cells to methotrexate takes the form of
      reversible growth arrest of the type of stress-induced senescence. In the present
      study it is shown that during C85 cell progression into methotrexate-induced
      senescence, dihydrofolate reductase, the primary intracellular target for the
      drug, is stabilized at the protein level and its enzymatic activity, assayed in
      crude cellular extracts, decreases by 2-fold. Dihydrofolate reductase inhibition
      results in an increase in dihydrobiopterin level and an ultimate decrease in the
      tetrahydrobiopterin: dihydrobiopterin ratio in senescent cells. Endothelial
      nitric oxide synthase expression declines. Despite concomitant upregulation of
      inducible nitric oxide synthase expression, no nitric oxide generation in
      senescent cells is detected. Progressing oxidative stress accompanies
      establishment of the state of senescence. DNA damage, in the form of double
      strand-breaks, occurs at the highest level at the senescence initiation phase and
      decreases as cells progress into the senescence maintenance phase.

PMID- 28739376
TI  - Functional inactivation of dorsal medial striatum alters behavioral flexibility
      and recognition process in mice.
AB  - Deficits in behavioral flexibility and recognition memory are commonly observed
      in mental illnesses and neurodegenerative diseases. Abnormality of the striatum
      has been implicated in an association with the pathology of these diseases.
      However, the exact roles of striatal heterogeneous structures in these cognitive
      functions are still unknown. In the present study, we investigated the effects of
      suppressing neuronal activity in the dorsomedial striatum (DMStr) and nucleus
      accumbens core (NAcC) on reversal learning and novelty recognition in mice. In
      addition, the locomotor activity, anxiety-like behavior and social interaction
      were analyzed. Neuronal inactivation was performed by expressing lentivirus
      mediated tetanus toxin (TeNT) in the target regions. The results showed that
      reversal learning was facilitated by neuronal inactivation in the DMStr but not
      the NAcC, which was attributable to accelerated extinction of acquired strategy
      but not to impaired memory retention. Furthermore, mice with NAcC inactivation
      spent more time exploring a novel object than a familiar one, comparable to
      control mice. In contrast, mice with DMStr inactivation exhibited no preference
      to a novel environment during the novel object or place recognition test. The
      DMStr mice also exhibited decreased anxiety level. No phenotypic effect was
      observed in the locomotion or social interaction in mice with either DMStr or
      NAcC inactivation. Altogether, these findings suggest that the DMStr but not the
      ventral area of the striatum plays a crucial role in learning and memory by
      coordinating spatial exploration as well as mediating information updating.

PMID- 28739377
TI  - Blood Hemostatic Changes During an Ultraendurance Road Cycling Event in a Hot
      Environment.
AB  - OBJECTIVE: This study aims to examine blood hemostatic responses to completing a
      164-km road cycling event in a hot environment. METHODS: Thirty-seven subjects
      (28 men and 9 women; 51.8+/-9.5 [mean+/-SD] y) completed the ride in 6.6+/-1.1
      hours. Anthropometrics (height, body mass [taken also during morning of the
      ride], percent body fat [%]) were collected the day before the ride. Blood
      samples were collected on the morning of the ride (PRE) and immediately after
      (IP) the subject completed the ride. Concentrations of platelet, platelet
      activation, coagulation, and fibrinolytic markers (platelet factor 4, beta
      thromboglobulin, von Willebrand factor antigen, thrombin-antithrombin complex,
      thrombomodulin, and D-Dimer) were measured. Associations between changes from PRE
      to IP-ride were examined as a function of event completion time and subject
      characteristics (demographics and anthropometrics). RESULTS: All blood hemostatic
      markers increased significantly (P < .001) from PRE to IP. After controlling for
      PRE values, finishing time was negatively correlated with platelet factor 4 (r =
      0.40; P = .017), while percent body fat (%BF) was negatively correlated with
      thrombin-antithrombin complex (r = -0.35; P = .038) and to thrombomodulin (r = 
      0.36; P = .036). In addition, male subjects had greater concentrations of
      thrombin-antithrombin complex (d = 0.63; P < .05) and natural logarithm
      thrombomodulin (d = 6.42; P < .05) than female subjects. CONCLUSION: Completing
      the 164-km road cycling event in hot conditions resulted in increased
      concentrations of platelet, platelet activation, coagulation, and fibrinolytic
      markers in both men and women. Although platelet activation and coagulation
      occurred, the fibrinolytic system markers also increased, which appears to
      balance blood hemostasis and may prevent clot formation during exercise in a hot
      environment.

PMID- 28739378
TI  - Succinate dehydrogenase (SDH) deficiency, Carney triad and the epigenome.
AB  - In this report, we review the relationship between succinate dehydrogenase (SDH)
      deficiency and the epigenome, especially with regards to two clinical conditions.
      Carney triad (CT) is a very rare disease with synchronous or metachronous
      occurrence of at least three different tumor entities; gastric gastrointestinal
      stromal tumor (GIST), paraganglioma (PGL), and pulmonary chondroma. This
      condition affects mostly females and it is never inherited. Another disease that
      shares two of the tumor components of CT, namely GIST and PGL is the Carney
      Stratakis syndrome (CSS) or dyad. CSS affects both genders during childhood and
      adolescence. We review herein the main clinical features and molecular mechanisms
      behind those two syndromes that share quite a bit of similarities, but one is non
      hereditary (CT) whereas the other shows an autosomal-dominant, with incomplete
      penetrance, inheritance pattern (CSS). Both CT and CSS are caused by the
      deficiency of the succinate dehydrogenase (SDH) enzyme. The key difference
      between the two syndromes is the molecular mechanism that causes the SDH
      deficiency. Most cases of CT show down-regulation of SDH through site-specific
      hyper-methylation of the SDHC gene, whereas CSS cases carry inactivating germline
      mutations within one of the genes coding for the SDH subunits A, B, C, or D
      (SDHA, SDHB, SDHC, and SDHD). There is only partial overlap between the two
      conditions (there are a few patients with CT that have SDH subunit mutations) but
      both lead to increased methylation of the entire genome in the tumors associated
      with them. Other tumors (outside CT and CSS) that have SDH deficiency are
      associated with increased methylation of the entire genome, but only in CT there
      is site-specific methylation of the SDHC gene. These findings have implications
      for diagnostics and the treatment of patients with these, often metastatic
      tumors.

PMID- 28739379
TI  - Ultrasound-Induced Bubble Clusters in Tissue-Mimicking Agar Phantoms.
AB  - Therapeutic ultrasound can drive bubble activity that damages soft tissues. To
      study the potential mechanisms of such injury, transparent agar tissue-mimicking
      phantoms were subjected to multiple pressure wave bursts of the kind being
      considered specifically for burst wave lithotripsy. A high-speed camera recorded
      bubble activity during each pulse. Various agar concentrations were used to alter
      the phantom's mechanical properties, especially its stiffness, which was varied
      by a factor of 3.5. However, the maximum observed bubble radius was insensitive
      to stiffness. During 1000 wave bursts of a candidate burst wave lithotripsy
      treatment, bubbles appeared continuously in a region that expanded slowly,
      primarily toward the transducer. Denser bubble clouds are formed at higher pulse
      repetition frequency. The specific observations are used to inform the
      incorporation of damage mechanisms into cavitation models for soft materials.

PMID- 28739380
TI  - ERK activation in the prefrontal cortex by acute apomorphine and apomorphine
      conditioned contextual stimuli.
AB  - The activation of extracellular signal-regulated kinase protein (ERK) has been
      linked to the adaptive responses to environmental changes and memory. The aim of
      this study was to measure ERK activation in primary dopamine projection areas
      namely, the prefrontal cortex and the nucleus accumbens, following a conditioned
      dopaminergic drug response. Initially, the effect of unconditioned apomorphine
      (2.0mg/kg) administration on ERK activation was measured and the results showed
      an increase in ERK for both brain regions. Subsequently, two experiments were
      conducted to assess ERK activation in these two areas following apomorphine
      conditioned contextual stimuli. In experiment 1, rats received 5 daily injections
      of 2.0mg/kg apomorphine or vehicle immediately prior to placement in an open
      field. After a withdrawal period of two days, a conditioning test was conducted,
      in which rats received a 30min non-drug test. Immediately after completion of the
      test, an immunohistochemical protocol was carried out to measure ERK activation.
      In experiment 2, a similar test protocol was performed except that the treatments
      were administered 30min following open-field tests (post-trial experiment). The
      results showed that the repeated apomorphine treatments given prior to testing
      induced conditioned effects. An increase in ERK activation was seen in the
      prefrontal cortex but not in the nucleus accumbens. There was no conditioning
      response observed in the post-trial experiment and no differential ERK
      activation. These observations implicate the prefrontal cortex in the associative
      neuro-adaptive changes induced by dopaminergic stimulation.

PMID- 28739381
TI  - Role of parafovea in blur perception.
AB  - The blur experienced by our visual system is not uniform across the visual field.
      Additionally, lens designs with variable power profile such as contact lenses
      used in presbyopia correction and to control myopia progression create variable
      blur from the fovea to the periphery. The perceptual changes associated with
      varying blur profile across the visual field are unclear. We therefore measured
      the perceived neutral focus with images of different angular subtense (from 4
      degrees  to 20 degrees ) and found that the amount of blur, for which focus is
      perceived as neutral, increases when the stimulus was extended to cover the
      parafovea. We also studied the changes in central perceived neutral focus after
      adaptation to images with similar magnitude of optical blur across the image or
      varying blur from center to the periphery. Altering the blur in the periphery had
      little or no effect on the shift of perceived neutral focus following adaptation
      to normal/blurred central images. These perceptual outcomes should be considered
      while designing bifocal optical solutions for myopia or presbyopia.

PMID- 28739382
TI  - Developmental trends in infant temporal processing speed.
AB  - Processing speed, which can be measured behaviorally in various sensory domains,
      has been shown to be a strong marker of central nervous system health and
      functioning in adults. Visual temporal processing speed (measured via critical
      flicker fusion [CFF] thresholds) represents the maximum speed at which the visual
      system can detect changes. Previous studies of infant CFF development have been
      limited and inconsistent. The present study sought to characterize the
      development of CFF thresholds in the first year of life using a larger sample
      than previous studies and a repeated measures design (in Experiment 2) to control
      for individual differences. Experiment 1 (n=44 infants and n=24 adults) used a
      cross-sectional design aimed at examining age-related changes that exist in CFF
      thresholds across infants during the first year of life. Adult data were
      collected to give context to infant CFF thresholds obtained under our specific
      stimulus conditions. Experiment 2 (N=28) used a repeated-measures design to
      characterize the developmental trajectory of infant CFF thresholds between three
      and six months of age, based on the results of Experiment 1. Our results reveal a
      general increase in CFF from three to four and one-half months of age, with a
      high degree of variability within each age group. Infant CFF thresholds at
      4.5months of age were not significantly different from the adult average, though
      a regression analysis of the data from Experiment 2 predicted that infants would
      reach the adult average closer to 6months of age. Developmental and clinical
      implications of these data are discussed.

PMID- 28739383
TI  - Patient-reported intestinal toxicity from whole pelvis intensity-modulated
      radiotherapy: First quantification of bowel dose-volume effects.
AB  - BACKGROUND AND PURPOSE: Intestinal toxicity is commonly experienced during whole
      pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer. The aim of
      the current study was to assess bowel dose-volume relationships for acute patient
      reported intestinal symptoms of patients treated with WPRT for prostate cancer.
      MATERIALS AND METHODS: Complete data of 206 patients were available; the median
      dose to pelvic nodes was 51.8Gy (range 50.4-54.4, 1.7-2Gy/fr). Intestinal
      symptoms were assessed as changes in the Inflammatory Bowel Disease Questionnaire
      scores relative to the Bowel Domain (IBDQ-B) between baseline and radiotherapy
      mid-point/end. The 25th percentiles of the most severe worsening from baseline
      (DeltaIBDQ-B) were set as end-points. The impact of bowel loops and sigmoid colon
      dose-volume/surface parameters as well as selected clinical parameters were
      investigated using multivariate logistic regression. RESULTS: Analyses were
      focused on the four questions showing a median DeltaIBDQ-B>0. No dose
      volume/surface parameters were predictive, other than DeltaIBDQ5>=3 (loose
      stools): when grouping patients according to bowel DVHs (high risk: V20>470cc,
      V30>245cc, V42>110cc; low risk: all the remaining patients), a two-variable model
      including high-risk DVH-shape (OR: 9.3) and age (protective, OR: 0.94) was
      assessed. The model showed good calibration (slope: 1.003, R2=0.92) and was found
      to be robust after bootstrap-based internal validation. CONCLUSIONS: Constraining
      the bowel loops may reduce the risk of loose stools. The risk is higher for
      younger patients.

PMID- 28739384
TI  - Tumor heterogeneity determined with a gammaH2AX foci assay: A study in human head
      and neck squamous cell carcinoma (hHNSCC) models.
AB  - PURPOSE: This study aimed to analyze the intra-tumoral heterogeneity of gammaH2AX
      foci in tumor specimens following ex vivo radiation to evaluate the potential of
      gammaH2AX foci as predictors for radiosensitivity. MATERIAL AND METHODS:
      gammaH2AX foci were quantified in tumor specimens of 3hHNSCC tumor models with
      known differences in radiosensitivity after reoxygenation in culture medium (10h,
      24h), single dose exposure (0Gy, 4Gy), and fixation 24h post-irradiation.
      Multiple, equally treated samples of the same tumor were analyzed for foci,
      normalized and fitted in a linear mixed-effects model. RESULTS: The ex vivo
      reoxygenation time had no significant effect on gammaH2AX foci counts. A
      significant intra model heterogeneity could be shown for FaDu (p=0.033) but not
      for SKX (p=0.167) and UT-SCC-5 (p=0.082) tumors, respectively. All tumor models
      showed a significant intra-tumoral heterogeneity between specimens of the same
      tumor (p<0.01) or among microscopic fields of a particular tumor specimen
      (p<0.0001). CONCLUSION: Similar results for ex vivo gammaH2AX foci between 10h
      and 24h reoxygenation time support the applicability of the assay in a clinical
      setting. The high intra-tumoral heterogeneity underlines the necessity of
      multiple analyzable samples per patient and therewith the need for an automated
      foci analysis.

PMID- 28739385
TI  - The Promise of Patient-Centered Text Messages for Encouraging HIV Testing in an
      Underserved Population.

PMID- 28739386
TI  - From silos to an innovative health care delivery and patient engagement model for
      children in Medicaid.

PMID- 28739387
TI  - Effect of cortex mori on pharmacokinetic profiles of main isoflavonoids from
      pueraria lobata in rat plasma.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Radix pueraria (the root of pueraria lobata
      (Wild.) Ohwi.), which contains a class of isoflavonoids as the main active
      components, as well as cortex mori (the root bark of Morus alba L), which
      contains abundant active alkaloids, have been employed for the treatment of
      diabetes in traditional Chinese medicine for centuries. In previous studies,
      pharmacodynamic synergistic reactions have been observed in compatible
      application of pueraria lobata isoflavonoids extracts (PLF) and cortex mori
      alkaloids extracts (CME) for inhibiting alpha-glycosidase activity. It has also
      been demonstrated that PLF can effectively slow down the absorption of active
      alkaloid from CME, so as to produce a higher effective concentration in small
      intestine for depressing the elevation of postprandial blood glucose through
      inhibiting alpha-glycosidase activity. AIM OF THE STUDY: In this study, the
      hypoglycemic effect of PLF, CME or CME-PLF mixture (the mixture of CME and PLF at
      a ratio of 1:6.3) was further evaluated through in vivo glucose tolerance
      studies. And the effect of CME on pharmacokinetic profiles of main isoflavonoids
      from PLF in rat plasma was investigated to further underlie compatibility
      mechanism of the two herbs. MATERIALS AND METHODS: Four groups of rats received
      an oral dose of starch solution alone or simultaneously with drugs by gavage
      feeding. The blood samples were collected to determine glucose concentrations by
      glucose oxidase method. In addition, another two groups of rats were orally
      administered with PLF or CME-PLF. The plasma samples were collected and assayed
      using an LC/MS/MS method for comparatively pharmacokinetic studies of five main
      isoflavonoids. RESULTS: For starch loading, co-administration of CME-PLF resulted
      in more potent inhibition effects on glucose responses compared to those by CME
      or PLF in rat. The isoflavonoids from PLF were rapidly absorbed, presenting
      similarly low concentrations in plasma. When CME was added, the Cmax and AUC of
      all the five isoflavonoids were increased. A phenomenon of double peaks was found
      for all analysts. The elimination rates of all the detected isoflavonoids were
      also slowed down with extension of t1/2. CONCLUSIONS: CME has been found to
      increase the absorption and delay the elimination of main isoflavonoids from PLF,
      which might result in higher concentrations of circulating active compounds for
      anti diabetes.

PMID- 28739388
TI  - Precise flux redistribution to glyoxylate cycle for 5-aminolevulinic acid
      production in Escherichia coli.
AB  - Microbial production of 5-aminolevulinic acid (ALA) has received much attention
      because of its potential in clinical applications. Overexpression along with the
      deciphering of regulation of the related enzymes and an analogue transporter
      yielded remarkable achievements in ALA production. Nonetheless, there is
      significant room for carbon flux optimization to enhance ALA production. The aim
      of this study was precise carbon flux optimization for high ALA production in
      Escherichia coli expressing the ALA biosynthetic pathway. Initially, genes hemA
      and hemL were overexpressed with strong promoters and synthetic 5'-untranslated
      regions (5'-UTRs). Then, the tricarboxylic acid (TCA) cycle was blocked to force
      carbon flux toward the ALA production pathway by deletion of sucA. Although the
      resulting strain showed a severe metabolic imbalance and low ALA production,
      further precise tuning of carbon flux to the glyoxylate cycle by varying the
      transcriptional strength of aceA led to substantially improved cell growth and
      ALA production. Thus, this precise tuning of the glyoxylate cycle in a
      quantitative manner should also enable efficient production of other value-added
      products derived from the TCA cycle.

PMID- 28739389
TI  - Association of recent major psychological stress with cardiac arrest: A case
      control study.
AB  - OBJECTIVE: We hypothesized that major psychological stress can be a risk factor
      for cardiac arrest and that effects are modified by elapsed time from specific
      stressful events. METHODS: Case-control study was conducted using database for
      cardiac arrest and emergency department (ED) visiting. Cases included adult
      patients with cardiac arrest with presumed cardiac etiology. Controls were
      matched with sex and age and visiting day from unintentional injured patients in
      same ED. The occurrence of 9 major life events (MLEs) such as a divorce within
      1year was used as a proxy measure of major psychological stress. A multivariable
      conditional logistic regression conducted to estimate the effect of MLEs on the
      risk of cardiac arrest according to the elapsed time from the MLEs. RESULTS: A
      total of 95 patients with cardiac arrest and 95 controls were assessed. In the
      case group, a total of 58 MLEs occurred, while 33 MLEs occurred in the control
      group during the same period. Recent MLEs were associated with a higher risk of
      sudden cardiac arrest (AOR 2.26 [95% CI:1.01-5.03]). The AORs of cardiac arrest
      were 4.65 (95% CI, 1.38-15.67) and 7.02 (95% CI, 2.03-24.48) among participants
      experiencing MLEs within the last 0-3months and those experiencing MLEs within
      the last 0-6months, respectively. Cardiac arrest and MLEs in participants
      experiencing MLEs between 7 and 12months prior showed no association (AOR 4.76
      [95% CI, 0.97-18.36]). CONCLUSIONS: MLEs were associated with cardiac arrest
      occurrence, and the effect was modified by the elapsed time from the MLEs.

PMID- 28739390
TI  - R-EME: RTLS-event mapping engine applications in emergency medicine.

PMID- 28739391
TI  - Blood culture contamination and ED overcrowding. Is there a connection?

PMID- 28739392
TI  - Large improvement of RF transmission efficiency and reception sensitivity for
      human in vivo31P MRS imaging using ultrahigh dielectric constant materials at 7T.
AB  - In vivo31P MRS provides a unique and important imaging tool for studying high
      energy phosphate metabolism and bioenergetics noninvasively. However, compared to
      1H MRS, 31P MRS with a relatively low gyromagnetic ratio (gamma) has a lower and
      limited sensitivity even at ultrahigh field. The proof of concept has been
      recently demonstrated that the use of high dielectric constant (HDC) materials
      between RF coil and object sample could increase MRI signal and reduce required
      RF transmission power for reaching the same RF pulse flip angle in the region of
      interest. For low-gamma MRS applications operated at relatively lower frequency,
      however, it demands the dielectric materials with a much higher permittivity for
      achieving optimal performance. We conducted a 31P MRS imaging study using ultra
      HDC (uHDC; with a relative permittivity of ~1200) material blocks incorporated
      with an RF volume coil at ultrahigh field of 7.0T. The experimental results from
      phantom and human calf muscle demonstrate that the uHDC technique significantly
      enhanced RF magnetic transmit field (B1+) and reception field (B1-) and the gain
      could reach up to two folds in the tissue near the uHDC blocks. The overall
      results indicate that the incorporation of the uHDC materials having an
      appropriate permittivity value with a RF coil can significantly increase
      detection sensitivity and reduces RF transmission power for X-nuclei MRS
      applications at ultrahigh field. The uHDC technology could provide an efficient,
      cost-effective engineering solution for achieving high detection sensitivity and
      concurrently minimizing tissue heating concern for human MRS and MRI
      applications.

PMID- 28739393
TI  - Rat brain digital stereotaxic white matter atlas with fine tract delineation in
      Paxinos space and its automated applications in DTI data analysis.
AB  - PURPOSE: To automatically analyze diffusion tensor images of the rat brain via
      both voxel-based and ROI-based approaches, we constructed a new white matter
      atlas of the rat brain with fine tracts delineation in the Paxinos and Watson
      space. MATERIALS AND METHODS: Unlike in previous studies, we constructed a
      digital atlas image from the latest edition of the Paxinos and Watson. This atlas
      contains 111 carefully delineated white matter fibers. A white matter network of
      rat brain based on anatomy was constructed by locating the intersection of all
      these tracts and recording the nuclei on the pathway of each white matter tract.
      Moreover, a compatible rat brain template from DTI images was created and
      standardized into the atlas space. To evaluate the automated application of the
      atlas in DTI data analysis, a group of rats with right-side middle cerebral
      artery occlusion (MCAO) and those without were enrolled in this study. RESULTS:
      The voxel-based analysis result shows that the brain region showing significant
      declines in signal in the MCAO rats was consistent with the occlusion position.
      CONCLUSION: We constructed a stereotaxic white matter atlas of the rat brain with
      fine tract delineation and a compatible template for the data analysis of DTI
      images of the rat brain.

PMID- 28739394
TI  - Ameliorative effect of alpha-tocopherol on polychlorinated biphenyl (PCBs)
      induced testicular Sertoli cell dysfunction in F1 prepuberal rats.
AB  - The study was conducted to investigate the protective role of alpha-tocopherol
      against polychlorinated biphenyls (PCBs) induced effect in Sertoli cell function
      of F1 prepuberal rats. Dams were grouped into six; each group consists of six
      animals. Group 1-control treated with corn oil as vehicle, group II- 0.5mgPCBs/kg
      bw/day, group III- 0.5mgPCBs/kg bw/day with alpha-tocopherol (50mg alpha
      tocopherol/kg bw/day), group IV- 1mgPCBs/kg bwt/day, group V- 1mgPCBs/kg bw/day
      with alpha-tocopherol (50mg alpha-tocopherol/kg bw/day) and group VI - alpha
      tocopherol alone treated orally from postpartum day1-20. Male offspring rats were
      euthanized on post natal day 21. Testes were collected for the histological
      examination and Sertoli cell isolation. The protein levels of follicle
      stimulating hormone receptor, androgen binding protein, androgen receptor,
      estrogen receptor alpha & beta, Inhibin-beta, transferrin, claudin-11, occludin,
      E-cadherin, connexin-43, c-fos, c-jun, SF1, USF1 & 2 were studied using western
      blot method. The testicular architecture was affected in the PCBs exposed rats
      but this effect was restored by alpha-tocopherol supplementation. PCBs decreased
      the protein levels of FSHR, AR, ABP, ERalpha & beta, transferrin, claudin-11,
      occludin, E-cadherin, connexin-43, c-fos, c-jun, SF1, USF1 & 2 whereas inhibin
      beta protein level was found to be increased in Sertoli cells. These results
      suggested that alpha-tocopherol has ameliorative role against PCBs induced
      testicular Sertoli cell dysfunction in F1 progeny.

PMID- 28739395
TI  - Sterigmatocystin induced apoptosis in human pulmonary cells in vitro.
AB  - Sterigmatocystin (ST) is generally recognized as a potential carcinogen, mutagen
      and teratogen. Studies showed that ST could induce adenocarcinoma of lung in mice
      in vivo and DNA damage, cell cycle arrest in a human immortalized bronchial
      epithelial cell line (BEAS-2B cells) and a human lung cancer cell line (A549
      cells) in vitro. Besides, ST could induce G2 arrest (cell cycle arrest in G2
      phase) in several other cells. Cell cycle arrest may be one of the common toxic
      effects of ST. As cells may undergo apoptosis or death due to cell cycle arrest,
      we wondered whether apoptosis is another common effect of ST in different cells
      in vitro. In the present study, we studied the effects of ST on proliferation and
      apoptosis in A549 cells and BEAS-2B cells with 3-(4,5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis (FCM). The
      MTT results showed that proliferation inhibition following ST treatment for 24h
      was observed in both A549 and BEAS-2B cells in vitro. And increased apoptosis by
      FCM was also found after ST treatment. Down-regulation of Bcl-2, up-regulation of
      Bax and the activation of caspase-3 after ST treatment were detected by western
      blotting analyses. The results in the present study are consistent with our
      previous results, which indicated that inducing apoptosis may be a common effect
      of ST in different cells in vitro.

PMID- 28739396
TI  - Genetic association of pro-inflammatory cytokine gene polymorphisms with coronary
      artery disease (CAD) in a North Indian population.
AB  - BACKGROUND: Cytokines regulate the expression of inflammatory molecules which
      destabilize the atheromatic plaques. This study focuses on studying the
      association of inflammatory cytokine polymorphisms like TNF-alpha -308 (G/A), TNF
      beta +252 (A/G), IL-6 -174 (G/C) and IL-6 -597 (G/A), and IFN-gamma +874 (T/A)
      with coronary artery disease (CAD) among north Indian patients. MATERIALS AND
      METHODS: 143 CAD and 137 normal healthy controls were recruited in this study.
      DNA extraction was carried out by high salting out method. TNF-alpha -308 (G/A)
      (rs1800797), TNF-beta +252 (A/G) (rs909253), IL-6 -174 (G/C) (rs1800795), IL6 
      597 (G/A) (rs1800797), and IFN-gamma +874 (T/A) (rs2430561) SNPs were genotyped
      by TaqMan(r)SNP genotyping assays. Different statistical analyses were performed
      using SPSS v 22.0 and SNPStats. p<=0.05 was considered significant. RESULTS:
      Significant risk association with CAD was found for TNF-alpha -308 (G/A) "A"
      allele (OR=5.6, CI 1.8-17.4, p=0.001) and TNF-beta +252 (A/G) "G" allele (OR=3.4,
      CI=1.9-6.0, p<0.001). However, no statistical significance was found for IL-6 
      174 (G/C) or IL6 -597 (G/A), with CAD. TNF-alpha -308 (G/A), and TNF-beta +252
      (A/G) haplotype "GG" "AG" increased CAD risk significantly (GG haplotype,
      adjusted OR=2.6, CI 1.4-5.0, p=0.003 and AG haplotype OR=8.5, CI 2.2-33.35,
      p=0.002) after adjustments for age, sex, TC, TG, HDL, APOB, smoking and diet.
      DISCUSSION: The present study found significant risk association for TNF-alpha 
      308 (G/A), and TNF-beta +252 (A/G) genotypes, alleles and haplotypes, with CAD in
      a North Indian population.

PMID- 28739397
TI  - Role of serum MMP-9 levels and vitamin D receptor polymorphisms in the
      susceptibility to coronary artery disease: An association study in Iranian
      population.
AB  - BACKGROUND: Data concerning the association of serum levels of vitamin D and
      metalloproteinases and vitamin D receptor gene polymorphism with coronary artery
      disease (CAD) is not fully demonstrated. The present study aimed to evaluate the
      association of vitamin D receptor gene polymorphism, serum levels of 25(OH)
      vitamin D and metalloproteinase-9 (MMP-9) with CAD. METHODS: 104 patients with
      CAD and 69 Non-CAD subjects were included in current study. Vitamin D receptor
      genotypes were determined by PCR-RFLP method. The 25(OH) vitamin D and MMP-9 were
      determined by ELISA assay. RESULTS: There was a significant reduction of vitamin
      D in CAD patients (P=0.001). The metalloproteinase 9 levels of CAD patient was
      increased significantly compared with controls (P=0.001). A significant reverse
      correlation also was found between MMP-9 concentration and 25(OH) vitamin D
      levels of patients (r=-0.28, P<0.001). In addition, we identified that VDR gene
      FokI polymorphism was significantly associated with CAD. Furthermore, MMP-9
      levels of CAD patients with ff genotype of FokI polymorphism was higher
      significantly than patients with FF and Ff genotypes. It has been also found that
      MMP-9 levels of CAD patients with ff genotype of FokI polymorphism was higher
      significantly than patients with FF and Ff genotypes. CONCLUSION: Our results
      indicated that 25(OH) vitamin D, MMP-9 levels and VDR gene FokI polymorphisms
      play a critical role in the development and progression of CAD and may contribute
      to susceptibility to CAD in Iranian populations.

PMID- 28739398
TI  - Transcriptome analysis of IFM-specific actin and myosin nulls in Drosophila
      melanogaster unravels lesion-specific expression blueprints across muscle
      mutations.
AB  - Muscle contraction is a highly fine-tuned process that requires the precise and
      timely construction of large protein sub-assemblies to form sarcomeres. Mutations
      in many genes encoding constituent proteins of this macromolecular machine result
      in defective functioning of the muscle tissue. However, the pathways underlying
      muscle degeneration, and manifestation of myopathy phenotypes are not well
      understood. In this study, we explored transcriptional alterations that ensue
      from the absence of the two major muscle proteins - myosin and actin - using the
      Drosophila indirect flight muscles. Our aim was to understand how the muscle
      tissue responds as a whole to the absence of either of the major scaffold
      proteins, whether the responses are generic to the tissue; or unique to the thick
      versus thin filament systems. Our results indicated that muscles respond by
      altering gene transcriptional levels in multiple systems active in muscle
      remodelling, protein degradation and heat shock responses. However, there were
      some responses that were filament-specific signatures of muscle degeneration,
      like immune responses, metabolic alterations and alterations in expression of
      muscle structural genes and mitochondrial ribosomal genes. These general and
      filament-specific changes in gene expression may be of relevance to human
      myopathies.

PMID- 28739399
TI  - A variant on chromosome 2p13.3 is associated with atopic dermatitis in Chinese
      Han population.
AB  - BACKGROUND: Multi-ancestry genome-wide association study (GWAS) has recently
      identified 11 new susceptibility loci for Atopic dermatitis (AD). The replication
      of these new susceptibility loci in different populations should not be ignored.
      OBJECTIVE: To examine whether these 11 new identified susceptibility loci are
      also associated with AD in the Chinese Han population. METHODS: These 11 variants
      were imputed using our genome-wide array dataset. The selected SNPs with
      suggestive signals were genotyped in a large-scale replication study with a total
      of 4619 cases and 10,789 controls using the Sequenom Massarray system.
      Association analyses were performed using PLINK 1.07 software. Results were
      combined across our previous AD-GWAS stage and the replication stage by meta
      analysis. Bioinformatic analysis was done to predict the possible causal gene.
      RESULTS: Of the 11 SNPs investigated, four SNPs showed suggestive association
      (P<0.05) in our previously published GWAS datasets. Association evidence for an
      intergenic variant rs112111458 at 2p13.3 with AD was replicated in Chinese Han
      population (P=7.37*10-7, OR=0.86), showing significance in Meta analysis of GWAS
      and replication study (Pmeta=8.18*10-08, OR=0.69). Further functional annotation
      by HaploReg indicated that transcriptional regulation activity exists at this
      locus for the CD207 gene in skin tissue. CONCLUSIONS: Our study confirmed a
      previously reported susceptibility loci in the Chinese Han population, which
      implicates CD207 might be a new susceptibility gene for AD and highlights the
      crucial role of immune responses in AD.

PMID- 28739400
TI  - Intraoperative and postoperative pain in cataract surgery.
AB  - Technologic improvements in cataract surgery have not only improved visual
      outcomes, but also have minimized intraoperative and postoperative pain. We
      review the mechanisms, risk factors, and management of intraoperative and
      postoperative pain. Summaries of less common sources of physiologic pain have
      been included to reinforce recognition of when pain represents an expected
      physiologic reaction to surgery as opposed to signaling a more serious
      complication. We also discuss various current and emerging anesthetic and
      analgesic modalities.

PMID- 28739401
TI  - A review of nasal, paranasal, and skull base tumors invading the orbit.
AB  - Tumors that invade the orbit are uncommon. The majority are meningiomas arising
      from the sphenoid ridge (66%). Others are bone and cartilage tumors arising from
      the surrounding bones of the orbit, pituitary adenomas, and epithelial tumors
      arising from the paranasal sinuses and nasal cavity. Meningiomas occur more often
      in women, whereas epithelial tumors have a predilection for men. Meningiomas and
      epithelial tumors typically present in the sixth decade of life, whereas bone
      tumors tend to affect individuals in their third decade of life. Patients often
      present with a combination of ophthalmological and otorhinolaryngological
      symptoms, including proptosis, pain, decreased visual acuity, restrictions in
      motility of the eye, epistaxis, and nasal obstruction. Sarcomas and benign bone
      and cartilage tumors arise from surrounding structures, whereas carcinomas
      usually arise from the paranasal sinuses. Surgery is the mainstay of treatment.
      Depending on the aggressiveness and histology of the tumor, surgery may be
      combined with radiation and chemotherapy. The prognosis is generally poor, but
      varies depending on histology and cell origin, size of the tumor, and degree of
      invasion. Meningiomas and benign bone tumors have the best prognoses. Sinonasal
      undifferentiated carcinomas, small-cell neuroendocrine carcinomas, osteosarcomas,
      and rhabdomyosarcomas have poorer prognoses.

PMID- 28739402
TI  - Graft detachment and rebubbling rate in Descemet membrane endothelial
      keratoplasty.
AB  - Descemet membrane endothelial keratoplasty (DMEK) is a selective replacement of
      dysfunctional endothelium with healthy donor Descemet membrane and endothelium.
      Although the donor preparation and surgical methods still remain a challenge,
      DMEK is gaining popularity in terms of early rehabilitation and visual outcomes.
      New and improved donor preparation techniques like prestripped DMEK tissues are
      being taken up rapidly because of less manipulation that is required in the
      surgical theatre. Donor graft delivery in the recipient eye has also been
      improved because of new products like prestripped and preloaded membranes. As
      DMEK is at its budding stage, only early outcomes have been known so far. Early
      graft detachment, rebubbling rates, and primary failures are still being studied
      in DMEK. As there are different techniques that are currently used for
      preparation and injection of the graft, it becomes difficult to judge the results
      based on specific inclusion and exclusion criteria. Graft detachment and
      rebubbling rates have been a huge challenge both during the surgery and also
      while reporting postoperative data. We highlight the importance of defining graft
      detachment and rebubbling rates and their surgical relevance, which may also have
      an impact on graft preparation and insertion techniques.

PMID- 28739403
TI  - Ileal Ureter Replacement Combined With Boari Flap-Psoas Hitch to Treat Full
      Length Ureteral Defects: Technique and Initial Experience.
AB  - OBJECTIVE: To evaluate the feasibility of ileal ureter replacement combined with
      Boari flap-psoas hitch procedure for the management of full-length ureteral
      defects (>20 cm). METHODS: Three patients diagnosed with full-length ureteral
      defect were treated with our technique performed by a single surgeon between
      January 2015 to January 2016. All the patients had borderline renal function
      preoperatively. In each case, the ureteral reconstruction was performed by
      combining ileal ureter replacement with Boari flap-psoas hitch. Data on
      indications for surgery, intraoperative and postoperative outcomes, and changes
      in renal function were collected. RESULTS: Surgery was performed successfully
      with an operation duration between 210 and 250 minutes. The mean estimated blood
      loss was 230 mL. The mean length of hospital stay was 11 days, and no major
      complications (grade >=3) occurred. Postoperative follow-up showed radiological
      resolution of hydronephrosis and improved renal function in all 3 patients.
      CONCLUSION: Ileal ureter replacement combined with Boari flap-psoas hitch is a
      feasible option for bridging full-length ureteral defects. This technique
      minimizes the length of ileal graft required as well as limitations concerning
      patient selection. Larger series with longer follow-up to confirm the value of
      the technique are warranted.

PMID- 28739404
TI  - Laparoscopic Partial Nephrectomy With Sequential Precise Tumor-specific Segmental
      Renal Artery Clamping for Multiple Ipsilateral Renal Tumors: A New Treatment
      Approach and Initial Experience.
AB  - OBJECTIVE: To present our surgical approach and initial experience of
      laparoscopic partial nephrectomy (LPN) with sequential precise tumor-specific
      segmental renal artery clamping in patients with multiple ipsilateral renal
      tumors. MATERIALS AND METHODS: Six patients with multiple ipsilateral renal
      tumors having imperative indications for nephron-sparing surgery underwent LPN
      with sequential precise tumor-specific segmental renal artery clamping from May
      2012 to September 2015. Patient demographics, perioperative variables, renal
      functions, and postoperative outcomes were reviewed. RESULTS: Overall 15 tumors
      in 6 patients underwent the sequential precise tumor-specific segmental renal
      artery clamping LPN without conversion to conventional main renal artery
      clamping, open surgery, or radical nephrectomy. No severe complication occurred.
      Mean size of the tumors was 2.5 cm (range 1.8-3.5). Mean tumor-related warm
      ischemia time was 17 min (range 13-22). The affected kidney functions minimally
      decreased at recent follow-up and restored 3 months later. No positive tumor
      margin or extrarenal invasion breakthrough renal capsule was observed after
      pathologic analysis. Over 12 months' follow-up, no local recurrence and distant
      metastasis were discovered in these cases postoperatively. CONCLUSION: LPN with
      sequential precise tumor-specific segmental renal artery clamping is a feasible
      approach for multiple ipsilateral renal tumors. It minimizes intraoperative warm
      ischemic injury and promotes encouraging postoperative function of the affected
      kidney.

PMID- 28739405
TI  - The Burden of Cystoscopic Bladder Cancer Surveillance: Anxiety, Discomfort, and
      Patient Preferences for Decision Making.
AB  - OBJECTIVE: To examine discomfort, anxiety, and preferences for decision making in
      patients undergoing surveillance cystoscopy for non-muscle-invasive bladder
      cancer (NMIBC). METHODS: Veterans with a prior diagnosis of NMIBC completed
      validated survey instruments assessing procedural discomfort, worry, and
      satisfaction, and were invited to participate in semistructured focus groups
      about their experience and desire to be involved in surveillance decision making.
      Focus group transcripts were analyzed qualitatively, using (1) systematic
      iterative coding, (2) triangulation involving multiple perspectives from
      urologists and an implementation scientist, and (3) searching and accounting for
      disconfirming evidence. RESULTS: Twelve patients participated in 3 focus groups.
      Median number of lifetime cystoscopy procedures was 6.5 (interquartile range 4
      10). Based on survey responses, two-thirds of participants (64%) experienced some
      degree of procedural discomfort or worry, and all participants reported
      improvement in at least 2 dimensions of overall well-being following cystoscopy.
      Qualitative analysis of the focus groups indicated that participants experience
      preprocedural anxiety and worry about their disease. Although many participants
      did not perceive themselves as having a defined role in decision making
      surrounding their surveillance care, their preferences to be involved in decision
      making varied widely, ranging from acceptance of the physician's recommendation,
      to uncertainty, to dissatisfaction with not being involved more in determining
      the intensity of surveillance care. CONCLUSION: Many patients with NMIBC
      experience discomfort, anxiety, and worry related to disease progression and not
      only cystoscopy. Although some patients are content to defer surveillance
      decisions to their physicians, others prefer to be more involved. Future work
      should focus on defining patient-centered approaches to surveillance decision
      making.

PMID- 28739406
TI  - Structural characterization and properties of konjac glucomannan and zein blend
      films.
AB  - A series of konjac glucomannan (KGM)/zein blend films were successfully prepared
      with zein in proportions 0-30%. The hydrophobicity of blend films were
      significantly stronger than pure KGM film, indicated by increased contact angle,
      swelling and solubility properties, and moisture absorption. Moreover, other
      properties including mechanical, thermal, water vapor and oxygen barrier were
      also found to be increased. FTIR indicated that hydrogen bond interactions and
      Maillard reaction occurred between KGM and zein molecules, and microstructural
      observations indicated that the aggregated zein was homogeneously dispersed in
      the KGM continuous matrix. However, these zein aggregations were larger with
      increased proportion of zein, leading to weakened molecular interactions with
      zein proportion >10%. A mixing ratio of KGM:zein=9:1 was suggested to provide
      best film properties. This research offers an alternative improvement for KGM
      based biodegradable films.

PMID- 28739407
TI  - Ultrasensitive transglutaminase based nanosensor for early detection of celiac
      disease in human.
AB  - A GQD/PAMAM nanohybrid modified on gold nanoparticles (AuNP) embedded in
      multiwalled carbon nanotubes (MWCNT) based immunosensor was developed for
      detection of celiac disease in human. The AuNP embedded in MWCNT were linked with
      thiol groups of cysteine and amino groups were further coupled with carboxyl
      moieties of graphene quantum dots (GQDs) using EDC-NHS cross-linking chemistry.
      To enhance the sensitivity of the sensor, polyamidoamine (PAMAM) dendrimer was
      attached with GQDs through carbodiimide coupling. The tissue transglutaminase
      (tTG) antigen was immobilized on PAMAM to form nanoprobe for sensing specific
      anti-tissue transglutaminase (anti-tTG) antibodies (immunoglobin A isotype) in
      human serum. The electrochemical changes after specific binding of antibody with
      antigen was measured cyclic voltammetry (CV) and differential pulse voltammetry
      (DPV). The modifications in sensor surface were characterized using FE-SEM. The
      sensor is highly specific to anti-tissue transglutaminase antibodies and showed
      negligible response to non-specific serum proteins. The sensitivity of the sensor
      was 1297.14MUA/cm2/pg with DPV and lower limit of detection of anti-tissue
      transglutaminase antibody was found 0.1fg per 6MUl.

PMID- 28739408
TI  - Inhibition of amyloid fibrillation and destabilization of fibrils of human gammaD
      crystallin by direct red 80 and orange G.
AB  - Inhibition of amyloid fibril formation by a lens protein namely human gammaD
      crystallin (HGD) under stressful conditions was targeted by using some small
      molecules like direct red 80 (DR), orange G (OG) and rhodamine B (RH). The
      protein itself was found to form matured fibrils after 48h of incubation at pH
      3.0 at 37 degrees C. Various fluorescence based assays (thioflavin T assay, ANS
      binding assay, intrinsic Trp fluorescence determination), circular dichroism and
      microscopic imaging techniques were used in the inhibition studies. Above studies
      unequivocally proved that DR had acted as the most potent inhibitor among these
      molecules and it was little better efficient than OG. RH had shown a moderate
      inhibition of HGD fibrillation. Microscopic images from fluorescence microscopy
      and transmission electron microscopy also substantiated our spectroscopic
      observations. These small molecules were not only capable to restrict the
      fibrillation, but they were also able to disassemble the mature and premature
      fibrils of HGD. Hydrophobic and aromatic interactions between the inhibitor
      molecules and partially unfolded HGD are likely to be responsible for exhibiting
      inhibition of protein fibrillation.

PMID- 28739409
TI  - Fabrication of Au(III) ion-imprinted polymer based on thiol-modified chitosan.
AB  - Au(III) ions were selectively extracted from aqueous media using Au(III) ion
      imprinted bio-adsorbent based on modified chitosan (Au-CMB). First, 2
      mercaptobenzaldehyde-chitosan Schiff base was prepared and interacted with
      Au(III) ions. The obtained polymeric Au(III) complex was then cross-linked by
      epichlorohydrin (ECH) before leaching the template Au(III) ions out of the cross
      linked matrix. During the synthetic procedures, the obtained chitosan derivatives
      were characterized by Elemental analysis, FTIR and NMR spectra. Moreover, the
      crystalline structures along with surface morphology of the fabricated polymeric
      materials were investigated using X-ray diffraction (XRD) spectra and scanning
      electron microscope (SEM), respectively. The Au(III) ions uptake studies
      indicated that the adsorption process was greatly influenced by pH and followed
      the pseudo-second-order kinetic mechanism. Furthermore, the adsorption was
      endothermic and the isotherms showed the best fit with Langmuir model with qm
      370+/-0.5 and 195+/-0.5mgg-1 in case of Au-CMB and NI-CMB, respectively.

PMID- 28739410
TI  - 1,3,5-Triazine-2,4,6-tribenzaldehyde derivative as a new crosslinking agent for
      synthesis of pH-thermo dual responsive chitosan hydrogels and their
      nanocomposites: Swelling properties and drug release behavior.
AB  - In this work, 1,3,5-triazine-2,4,6-tribenzaldehyde was synthesized and chosen as
      the cross-linking agent for preparation of novel thermo- and pH-responsive
      hydrogels based on chitosan. The cross-linking proceeds through formation of
      imine bond by reaction of amino groups of chitosan with aldehyde groups of the
      cross-linker. The various amounts (6, 10, 14% w/w) of the cross-linker were used
      with respect to chitosan to produce three 1,3,5-triazine-2,4,6-tribenzaldehyde
      cross-linked chitosans. Then, their hydrogel nanocomposites were prepared by
      crosslinking of chitosan with 1,3,5-triazine-2,4,6-tribenzaldehyde in the
      presence of 0.1% and 0.3% (w/w) multi-walled carbon nanotubes (MWCNTs). The
      structure and properties of the hydrogels and their nanocomposites were
      characterized by FT-IR, 1H NMR and scanning electron microscopy (SEM). The
      swelling behavior of prepared hydrogels and their nanocomposites at different pHs
      and temperatures was investigated. The results showed that they exhibit a pH and
      temperature-responsive swelling ratio. The swelling behavior of the prepared
      chitosan hydrogels was strongly dependent on the amounts of cross-linker and
      MWCNTs. In vitro controlled release behavior of metronidazole model drug was
      studied with prepared hydrogels and nanocomposite hydrogels. The pH, temperature
      and wt% of MWCNTs were found to strongly influence the drug release behavior of
      the hydrogels.

PMID- 28739411
TI  - Impact of heat-moisture and annealing treatments on physicochemical properties
      and digestibility of starches from different colored sweet potato varieties.
AB  - The objective of this study is to investigate the change in physicochemical
      properties and digestibility of starches isolated from colored sweet potato
      varieties under heat-moisture treatment (HMT) or annealing treatment (ANN). The
      results showed that morphology and X-ray diffraction patterns of the sweet potato
      starches remained unchanged after the HMT or ANN. The HMT significantly reduced
      peak viscosity, breakdown and setback and significantly increased pasting
      temperature, trough and final viscosities of the sweet potato starches. The
      swelling powers and solubility of the heat-moisture treated starches were
      significantly lower than those of the native or annealed starches. The decreased
      rapid digestible starch and the increased slowly digestible and resistant starch
      contents of the sweet potato starches after HMT or ANN as compared to those of
      the native starches were observed. The resistant starch (RS) contents of the heat
      moisture treated sweet potato starches were in a range of 30.6-39.3%,
      significantly higher than those of the annealed starches (28.8-32.0%). The strong
      impact of the HMT on physicochemical properties and RS formation of the sweet
      potato starches compared to the ANN might be due to the high stability of the
      occurred interactions between starch molecules and amylopectin chains during
      treatment.

PMID- 28739412
TI  - Alginate enhances Toll-like receptor 4-mediated phagocytosis by murine RAW264.7
      macrophages.
AB  - Alginate is a naturally acidic polysaccharide consisting alternately of beta-d
      mannuronic acid and alpha-l-guluronic acid with 1, 4-glycosidic linkages and is
      derived from brown seaweeds. Herein, the effect of alginate on the promotion of
      macrophage phagocytosis and the corresponding molecular mechanisms were
      investigated in murine RAW264.7 cells. Alginate could enhance the intracellular
      phagocytosis of gold nanoparticles (AuNPs), fluorescent microspheres and
      immunoglobulin G (IgG)-opsonized Staphylococcus aureus (S. aureus). Moreover,
      alginate increased Toll-like receptor 4 (TLR4) expression and activated the
      Akt/nuclear factor-kappaB (NF-kappaB) and p38 mitogen-activated protein kinase
      (MAPK) signalling pathways. Alginate-promoted phagocytosis was suppressed by the
      addition of inhibitors of TLR4, NF-kappaB and p38 MAPK and by TLR4 gene
      knockdown, indicating the involvement of these key components. This work is the
      first to propose that alginate promotes phagocytosis via upregulating TLR4
      expression and stimulating the Akt/NF-kappaB and p38 MAPK signalling pathways,
      which may contribute to the capacity of alginate to activate macrophages.

PMID- 28739413
TI  - Production of recombinant flagellin to develop ELISA-based detection of
      Salmonella Enteritidis.
AB  - Food-borne diseases, caused by the pathogenic bacteria, are highly prevalent in
      the world. Salmonella is one of the most important bacterial genera responsible
      for this. Salmonella Enteritidis (SE) is one of the non-typhoid Salmonellae that
      can be transmitted to human from poultry products, water, and contaminated food.
      In recent years, new and rapid detection methods such as enzyme-linked
      immunosorbent assay (ELISA) and polymerase chain reaction (PCR) have been
      developed. In this study, recombinant FliC (rFliC) was produced to be used as an
      antigen. The immunization was conducted in mice with the purified recombinant
      FliC (rFliC). The mice were subcutaneously immunized with rFliC and elicited
      significant rFliC specific serum IgG antibodies. An indirect ELISA system was
      established for the detection of Salmonella Enteritidis. Our results confirmed
      that the recombinant flagellin can be one of the excellent indicators for the
      detection of Salmonella Enteritidis.

PMID- 28739414
TI  - Conservative Surgery for Adenomyosis and Results: A Systematic Review.
AB  - The traditional treatment for women with symptomatic adenomyosis is hysterectomy.
      However, reproductive-aged women should be managed with less invasive treatments
      including medical treatment. For patients who are refractory or unsuitable to
      long-term medical treatment or those with focal adenomyoma, conservative
      surgeries could be offered. The objective of our study was to review available
      conservative surgeries for the treatment of adenomyosis, their complications, and
      the rates of success and recurrence. In this systematic review we evaluated 27
      studies; 10 prospective and 17 retrospective studies including a total of 1398
      patients. The results showed that excision of adenomyosis is effective for
      symptom control such as menorrhagia and dysmenorrhea and most probably for
      adenomyosis-related infertility. For preserving fertility and relieving symptoms,
      medical treatment is usually the first choice, whereas excisional surgery could
      be performed for refractory adenomyosis. The results show that over three-fourths
      of women will experience symptom relief after conservative surgery. The pregnancy
      rates after conservative surgical treatment vary widely. However, three-fourths
      of them conceived after surgery with or without adjuvant medical treatment.
      Depending on the duration of follow-up, recurrence rates differ from no
      recurrence to almost one-half of patients. Conservative surgery for adenomyosis
      improves pelvic pain, abnormal uterine bleeding, and possibly fertility. The best
      method of surgery is yet to be seen.

PMID- 28739416
TI  - Comparison of non-invasive assessments of strength of the proximal femur.
AB  - It is not clear which non-invasive method is most effective for predicting
      strength of the proximal femur in those at highest risk of fracture. The primary
      aim of this study was to compare the abilities of dual energy X-ray
      absorptiometry (DXA)-derived aBMD, quantitative computed tomography (QCT)-derived
      density and volume measures, and finite element analysis (FEA)-estimated strength
      to predict femoral failure load. We also evaluated the contribution of cortical
      and trabecular bone measurements to proximal femur strength. We obtained 76 human
      cadaveric proximal femurs (50 women and 26 men; age 74+/-8.8years), performed
      imaging with DXA and QCT, and mechanically tested the femurs to failure in a
      sideways fall configuration at a high loading rate. Linear regression analysis
      was used to construct the predictive model between imaging outcomes and
      experimentally-measured femoral strength for each method. To compare the
      performance of each method we used 3-fold cross validation repeated 10 times. The
      bone strength estimated by QCT-based FEA predicted femoral failure load
      (R2adj=0.78, 95%CI 0.76-0.80; RMSE=896N, 95%CI 830-961) significantly better than
      femoral neck aBMD by DXA (R2adj=0.69, 95%CI 0.66-0.72; RMSE=1011N, 95%CI 952
      1069) and the QCT-based model (R2adj=0.73, 95%CI 0.71-0.75; RMSE=932N, 95%CI 879
      985). Both cortical and trabecular bone contribute to femoral strength, the
      contribution of cortical bone being higher in femurs with lower trabecular bone
      density. These findings have implications for optimizing clinical approaches to
      assess hip fracture risk. In addition, our findings provide new insights that
      will assist in interpretation of the effects of osteoporosis treatments that
      preferentially impact cortical versus trabecular bone.

PMID- 28739415
TI  - Human Factors Evaluation of Surgeons' Working Positions for Gynecologic Minimal
      Access Surgery.
AB  - STUDY OBJECTIVE: To investigate work-related musculoskeletal disorders (WRMSD) in
      gynaecological minimal access surgery (MAS), including bariatric (plus size)
      patients DESIGN: Mixed methods (Canadian Task Force classification III). SETTING:
      Teaching hospital in the United Kingdom. MEASUREMENTS: Survey, observations
      (anthropometry, postural analysis), and interviews. RESULTS: Work-related
      musculoskeletal disorders (WRMSDs) were present in 63% of the survey respondents
      (n = 67). The pilot study (n = 11) identified contributory factors, including
      workplace layout, equipment design, and preference of port use (relative to
      patient size). Statistically significant differences for WRMSD-related posture
      risks were found within groups (average-size mannequin and plus-size mannequin)
      but not between patient size groups, suggesting that port preference may be
      driven by surgeon preference (and experience) rather than by patient size.
      CONCLUSION: Some of the challenges identified in this project need new
      engineering solutions to allow flexibility to support surgeon choice of operating
      approach (open, laparoscopic or robotic) with a workplace that supports
      adaptation to the task, the surgeon, and the patient.

PMID- 28739417
TI  - Neutron tomographic imaging of bone-implant interface: Comparison with X-ray
      tomography.
AB  - Metal implants, in e.g. joint replacements, are generally considered to be a
      success. As mechanical stability is important for the longevity of a prosthesis,
      the biological reaction of the bone to the mechanical loading conditions after
      implantation and during remodelling determines its fate. The bone reaction at the
      implant interface can be studied using high-resolution imaging. However, commonly
      used X-ray imaging suffers from image artefacts in the close proximity of metal
      implants, which limit the possibility to closely examine the bone at the bone
      implant interface. An alternative ex vivo 3D imaging method is offered by neutron
      tomography. Neutrons interact with matter differently than X-rays; therefore,
      this study explores if neutron tomography may be used to enrich studies on bone
      implant interfaces. A stainless steel screw was implanted in a rat tibia and left
      to integrate for 6weeks. After extracting the tibia, the bone-screw construct was
      imaged using X-ray and neutron tomography at different resolutions. Artefacts
      were visible in all X-ray images in the close proximity of the implant, which
      limited the ability to accurately quantify the bone around the implant. In
      contrast, neutron images were free of metal artefacts, enabling full analysis of
      the bone-implant interface. Trabecular structural bone parameters were quantified
      in the metaphyseal bone away from the implant using all imaging modalities. The
      structural bone parameters were similar for all images except for the lowest
      resolution neutron images. This study presents the first proof-of-concept that
      neutron tomographic imaging can be used for ex-vivo evaluation of bone
      microstructure and that it constitutes a viable, new tool to study the bone
      implant interface tissue remodelling.

PMID- 28739418
TI  - Deficiency of DGCR8 increases bone formation through downregulation of miR-22
      expression.
AB  - MicroRNAs (miRNA) significantly contribute to bone formation by post
      transcriptional regulation of gene expression. Mature miRNAs are generated
      following sequential cleavage by DROSHA/DGCR8 and DICER. However, recent studies
      have identified that some miRNAs require only one of these enzymes. Most studies
      seeking to clarify the role of miRNA during bone formation have been performed
      using DICER deletion strategies, but little is known regarding the role of DGCR8.
      To study the function of DGCR8 in osteogenesis, we generated mice in which Dgcr8
      is conditionally deleted in osteoprogenitor cells by Col1a1-Cre. Dgcr8-cKO mice
      showed increased bone volume (BV/TV), trabecular number (Tb/N), and trabecular
      thickness (Tb.Th), but decreased trabecular separation (Tb.Sp) in the femur. Von
      Kossa, tartrate-resistant acid phosphatase staining, and calcein double labeling
      identified that osteoblast activity is increased in Dgcr8-cKO mice. In an effort
      to elucidate a detailed cellular mechanism, we found that miR-22 was
      downregulated in Dgcr8-cKO mice, leading to upregulation of the osteocalcin
      transcript, a key marker of osteoblasts. Interestingly, the mRNA expression level
      of Dgcr8 was decreased during osteoblast differentiation. Taken together, these
      results strongly indicate that DGCR8-dependent generation of miR-22 is essential
      for bone formation and that miR-22 could be a therapeutic target for individuals
      with bone disease.

PMID- 28739419
TI  - Retinal Nonperfusion in the Posterior Pole Is Associated With Increased Risk of
      Neovascularization in Central Retinal Vein Occlusion.
AB  - PURPOSE: To review the definition of ischaemic central retinal vein occlusion
      (CRVO) and stratify the risk of neovascular complication based on wider areas of
      visible retinal non-perfusion. DESIGN: Retrospective consecutive case series and
      image analysis study. METHODS: Setting: Moorfields Eye Hospital, London, United
      Kingdom. STUDY POPULATION: Forty-two consecutive treatment-naive eyes with CRVO
      imaged with ultra-widefield angiography with a minimum of 12 months follow-up.
      OBSERVATION PROCEDURE: The spatial location and total area of retinal
      nonperfusion (measured in disc areas, DA) were determined using the validated
      concentric rings method. The area was corrected for projection distortion. The
      images were graded by 2 retinal physicians and average measurements used. MAIN
      OUTCOME MEASURES: Development of neovascular complications. RESULTS: The
      percentage of eyes developing new vessels increased from none in eyes with less
      than 10 DA of nonperfusion in total to 14.3% in eyes with 10-30 DA, 20.0% for 30
      75 DA, and 80% risk with 75-150 DA of nonperfusion. From 13 (31.0%) eyes with a
      perfused posterior pole (an area encompassing a 5 disc diameter radius centered
      at the fovea) and more than 10 DA of nonperfusion isolated in the periphery
      (beyond the posterior pole), only 1 (7.7%) eye developed new vessels, odds ratio
      (OR) 0.12 [95% confidence interval (CI): 0.01, 1.03]. Comparatively, for 13
      (31.0%) eyes with more than 10 DA of nonperfusion in the posterior pole, 11
      (84.6%) developed new vessels, OR 74.25 [95% CI: 9.26, 595.30], P < .001.
      CONCLUSION: With ultra-widefield angiography, we have ascertained that posterior
      pole nonperfusion of more than 10 DA remains the key risk factor for new vessel
      development compared to areas of nonperfusion confined to the periphery.

PMID- 28739420
TI  - Long-term Visual Outcomes Comparing Descemet Stripping Automated Endothelial
      Keratoplasty and Penetrating Keratoplasty.
AB  - PURPOSE: To compare 5-year visual acuity and refraction outcome in Descemet
      stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty
      (PK) for Fuchs endothelial dystrophy (FED) or bullous keratopathy (BK) in Asian
      eyes. DESIGN: Prospective interventional case series. METHODS: We analyzed 828
      consecutive cases of DSAEK (423) or PK (405) for FED and BK from the Singapore
      Cornea Transplant Registry performed from 1991 to 2011. Our main outcome measures
      were best spectacle-corrected visual acuity (BSCVA) with astigmatism (cylinder)
      and spherical equivalent (SE) over 5 years of follow-up. RESULTS: Mean age was
      67.5 +/- 11.5 years (50.1% male, 49.9% female) and majority was Chinese (76.6%, n
      = 634) in our multiracial Asian population. DSAEK eyes had significantly better
      BSCVA (P < .001-.037) with lower SE (P < .001-.017) and cylinder (P < .001),
      independent of surgical indication, compared to PK over 5 years. DSAEK was
      superior to PK over 5 years (P < .001-.026) in FED, but only over 3 years in BK
      (P < .001-.031). DSAEK in FED eyes had significantly better BSCVA compared to BK
      eyes (P = .006 at 4-year follow-up). DSAEKs with preoperative BSCVA < 1.3 logMAR
      had significantly better visual outcomes than cases with >= 1.3 logMAR (P < .001
      .042). PKs had significantly higher postoperative refractive correction than
      DSAEKs, with no significant influence of the surgery indication. CONCLUSIONS: In
      our study cohort, DSAEK provided significantly better long-term BSCVA and lower
      astigmatism than PK over 5 years of follow-up. Visual outcomes of DSAEK for FED
      were better than BK. In some analyses for years 1-3, analysis of covariance
      adjustment indicated that this DSAEK-associated better long-term BSCVA was
      independent of better preoperative vision in DSAEK eyes.

PMID- 28739421
TI  - Whole genome sequencing of Mycobacterium bovis to obtain molecular fingerprints
      in human and cattle isolates from Baja California, Mexico.
AB  - OBJECTIVES: To determine genetic diversity by comparing the whole genome
      sequences of cattle and human Mycobacterium bovis isolates from Baja California.
      METHODS: A whole genome sequencing strategy was used to obtain the molecular
      fingerprints of 172 isolates of M. bovis obtained from Baja California, Mexico;
      155 isolates were from cattle and 17 isolates were from humans. Spoligotypes were
      characterized in silico and single nucleotide polymorphism (SNP) differences
      between the isolates were evaluated. RESULTS: A total of 12 M. bovis spoligotype
      patterns were identified in cattle and humans. Two predominant spoligotypes
      patterns were seen in both cattle and humans: SB0145 and SB1040. The SB0145
      spoligotype represented 59% of cattle isolates (n=91) and 65% of human isolates
      (n=11), while the SB1040 spoligotype represented 30% of cattle isolates (n=47)
      and 30% of human isolates (n=5). When evaluating SNP differences, the human
      isolates were intimately intertwined with the cattle isolates. CONCLUSIONS: All
      isolates from humans had spoligotype patterns that matched those observed in the
      cattle isolates, and all human isolates shared common ancestors with cattle in
      Baja California based on SNP analysis. This suggests that most human tuberculosis
      caused by M. bovis in Baja California is derived from M. bovis circulating in
      Baja California cattle. These results reinforce the importance of bovine
      tuberculosis surveillance and control in this region.

PMID- 28739422
TI  - Silent emergence of Mayaro and Oropouche viruses in humans in Central Brazil.

PMID- 28739423
TI  - Sociodemographic and economic characteristics of susceptibility to rubella among
      women preparing for pregnancy in rural China.
AB  - OBJECTIVES: Infection with rubella virus during pregnancy can result in
      congenital defects and adverse pregnancy outcomes. The risk of rubella infection
      is greatly determined by the level of rubella antibodies in the serum. A survey
      of rubella antibody seronegativity rates was conducted in 780 000 women in rural
      China who were planning a pregnancy, in order to evaluate the herd susceptibility
      in different age groups and by high, middle, and low GDP per capita regions.
      METHODS: In order to evaluate the herd susceptibility to rubella, a nationwide
      population-based study of rural Chinese women who were planning to have a baby
      and who were aged 21-49 years was instigated. As a part of the National Free Pre
      conception Health Examination Project covering 29 provinces in 2012, a physical
      check-up program was provided to women who planned to become pregnant within the
      next 6 months. All medical data were from serological samples tested by ELISA,
      and the participants' immunity status was categorized based on levels of rubella
      antibodies. Economic data were also collected to explore the association between
      herd susceptibility and socioeconomic characteristics in the women of
      childbearing age. RESULTS: A total 264 306 of 782 293 recruited women preparing
      for pregnancy tested susceptible to rubella (33.79%). The seronegativity rate in
      women with a history of vaccination was significantly lower than that in women
      who had not received the vaccination or did not know their vaccination history
      (23.76%, 33.70%, and 35.68%, respectively). The seronegativity rates were 26.89%,
      37.86%, and 32.61% in high, middle, and low GDP per capita areas, respectively.
      After stratified analysis and adjusting for other factors by multiple logistic
      regression, the lower seronegativity rates in women in high GDP per capita
      regions compared to women in middle and low GDP per capita regions remained in
      the different age groups and subgroups of immunization history. CONCLUSIONS:
      There is a clear difference in rubella-specific susceptibility among rural women
      preparing for pregnancy of different sociodemographic and economic backgrounds.
      The number of rubella-susceptible rural women preparing for pregnancy, especially
      in relatively low GDP per capita regions in China, was high. Offering rubella
      vaccination to women who are rubella-susceptible and who plan to become pregnant
      should become one of the priorities in the field of public health work in China.

PMID- 28739424
TI  - Respiratory viruses in transplant recipients: more than just a cold. Clinical
      syndromes and infection prevention principles.
AB  - OBJECTIVES: The aim of this review is to provide updated information on the
      clinical spectrum, treatment options, and infection prevention strategies for
      respiratory viral infections (RVIs) in both solid organ (SOT) and hematopoietic
      stem cell transplant (HSCT) patients. METHODS: The MEDLINE and PubMed databases
      were searched for literature regarding the aforementioned aspects of RVIs, with
      focus on respiratory syncytial virus, adenovirus, influenza virus, parainfluenza
      virus, human metapneumovirus, and rhinovirus. RESULTS: Compared to
      immunocompetent hosts, SOT and HSCT patients are much more likely to experience a
      prolonged duration of illness, prolonged shedding, and progression of upper
      respiratory tract disease to pneumonia when infected with respiratory viruses.
      Adenovirus and respiratory syncytial virus tend to have the highest mortality and
      risk for disseminated disease, but all the RVIs are associated with higher
      morbidity and mortality in these patients than in the general population. These
      viruses are spread via direct contact and aerosolized droplets, and nosocomial
      spread has been reported. CONCLUSIONS: RVIs are associated with high morbidity
      and mortality among SOT and HSCT recipients. Management options are currently
      limited or lack strong clinical evidence. As community and nosocomial spread has
      been reported for all reviewed RVIs, strict adherence to infection control
      measures is key to preventing outbreaks.

PMID- 28739425
TI  - Associations of isokinetic and isotonic knee strength with knee function and
      activity level after anterior cruciate ligament reconstruction: a prospective
      cohort study.
AB  - BACKGROUND: Although isokinetic dynamometry often serves as a reference to assess
      the concurrent validity of weight-machine isotonic strength testing, it is
      unknown whether isokinetic knee strength is associated with knee function and
      activity level more strongly than isotonic knee strength in patients with an
      anterior cruciate ligament reconstruction (ACLR). This study aimed to compare the
      associations of isokinetic and isotonic knee strength with knee function and work
      and-sports activity levels in patients with ACLR. METHODS: One-hundred and six
      patients with a unilateral ACLR participated. At three months post-ACLR,
      isokinetic quadriceps and hamstrings strength was measured using an isokinetic
      dynamometer whilst isotonic strength was measured using weight machines. At six
      months post-ACLR, patients performed the single-leg hop-for-distance test. Self
      reported knee function and work-and-sports activity levels were assessed by the
      Lysholm Knee Score and Tegner Activity Score, respectively. RESULTS: In
      multivariable analyses, isotonic and isokinetic quadriceps strength limb symmetry
      indices (LSIs) were significantly associated with all outcomes (P<=0.03) and had
      comparable predictive performance. Isotonic and isokinetic hamstrings strength
      LSIs were significantly associated with Lysholm scores (P<=0.03) and isotonic
      hamstrings strength was additionally significantly associated with hop-for
      distance LSI (P=0.01). CONCLUSIONS: Weight machine-derived isotonic quadriceps
      strength was independently and consistently associated with knee function and
      work-and-sport activity level post-ACLR. Isokinetic knee strength was not more
      strongly associated than isotonic knee strength with the various outcomes. These
      findings have logistic and economic implications because the isokinetic
      dynamometer system is relatively expensive and its operation requires more
      logistic effort and technical skills.

PMID- 28739426
TI  - Incorporating oral health into interprofessional care teams for patients with
      Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder that
      primarily affects the motor system. However, non-motor symptoms such as
      cognitive, autonomic, sleep-related and sensory dysfunctions are often reported.
      A subgroup of non-motor symptoms, oropharyngeal problems, also affects these
      patients in ways that greatly deteriorate quality of life. Each patient may
      develop a different set of non-motor symptoms, making interprofessional
      collaboration among health care providers a must to treat patients with PD. In
      this review, we argue that dental health professionals must be included in this
      interprofessional health care team. Patients with PD are at a higher risk for
      developing oral health problems that can exacerbate or be exacerbated by other
      non-motor symptoms, such as mental health and dysphagia This accelerates decline
      in quality of life and even increases the risk of death by aspiration pneumonia.
      Dentists can create preventive oral health plans as soon as a diagnosis is made
      and promptly treat a patient's dental problems, preventing them from affecting
      other health areas. We describe major oral health concerns and how health
      professionals and dentists can participate and collaborate to improve the health
      of patients with PD.

PMID- 28739427
TI  - The impact of genetic variation in IL28B, IFNL4 and HLA genes on treatment
      responses against chronic hepatitis C virus infection.
AB  - Single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B),
      interferon lambda 4 (IFNL4) and the human leukocyte antigen (HLA) gene are
      associated with treatment responses in patients with chronic hepatitis C (CHC)
      virus infection treated with pegylated interferon-alpha and ribavirin (pegIFN
      alpha/RBV). We compared the role of IL28B SNPs (rs12979860, rs12980275, and
      rs8099917), IFNL4 ss469415590 and HLA rs4273729 with treatment outcomes in
      patients with CHC virus. A total of 520 Iranian patients with CHC infection were
      enrolled. SNPs in IL28B, IFNL4 ss469415590 and HLA rs4273729 were genotyped by
      PCR-restriction fragment length polymorphism, TaqMan(r) Real-Time PCR and direct
      sequence. Out of 520 CHC treatment-naive patients, 42.9% were infected with HCV
      1a, 15.4% with HCV-1b, 9.8% with HCV-2, and 31.9% with HCV-3a. Rapid virologic
      response (RVR), complete early virologic response (cEVR), and sustained virologic
      response (SVR) were 53.3%, 73.8%, and 66.7%, respectively. Multivariate logistic
      regression analysis showed that IL28B rs12980275 and IFNL4 ss469415590 in all HCV
      genotypes were associated with RVR. In addition, IL28B rs12979860 and RVR in all
      HCV genotypes and IL28B rs12980275, IFNL4 ss469415590, and HLA rs4273729 in HCV
      subtypes 1a, 1b, and 3a correlated with cEVR. In patient's achieving-SVR, IL28B
      rs12980275, and RVR in all HCV genotypes and IL28B rs12979860, IFNL4 ss469415590,
      and HLA rs4273729 in HCV subtypes 1a, 1b, and 3a were the powerful predictor
      factors. As the first report of its kind published in Iran, we indicated that
      beside IL28B SNPs and HLA rs4273729, IFNL4 ss469415590 was a powerful predictor
      factor for RVR, cEVR and SVR. Genotyping these SNPs may be a helpful priority in
      the treatment of patients with HCV infection, especially in countries where
      access to triple or double therapy with a viral protease inhibitor is limited.

PMID- 28739428
TI  - Novel class 1 Integrons and sequence types in VIM-2 and VIM-11-producing clinical
      strains of Enterobacter cloacae.
AB  - All VIM-producing Enterobacteriaceae (six Enterobacter cloacae) submitted to the
      Argentinian Reference Laboratory in Antimicrobial Resistance in the period 2008
      13 were characterized. The isolates were referred from 6 nosocomial institutions
      located in 5 different cities across the country. All isolates showed carbapenem
      disk diffusion inhibition zones <=22mm and synergism between a carbapenem disk
      and EDTA/SMA. The six isolates were PCR positive for blaVIM. Imipenem MICs were
      <=1 to 8MUg/ml. Typing by PFGE and MLST distinguished six pulsotypes and sequence
      types with blaVIM located on novel class 1 integron arrays: ECL-1: ST182, In883;
      ECL-2, ST90, In885; ECL-3, ST88, In346 with blaVIM-11; ECL-4, ST184, In900; ECL
      5, ST749-new, In900; ECL-6, ST91 and uncharacterized In. Only ECL-2 was able to
      transfer blaVIM-2 to E. coli J53 by biparental conjugation. blaVIM was located in
      plasmids of 53-82Kb and in the chromosome (ECL-1 and ECL-5). The diversity of
      clones, class 1 integrons, plasmids and location of blaVIM, reveals the
      plasticity of the genetic elements described and highlights the importance of
      surveillance programs as tools to identify the transmission of these highly
      resistant metallo-beta-lactamase-producing Enterobacteriaceae.

PMID- 28739429
TI  - llex paraguariensis decreases oxidative stress in bone and mitigates the damage
      in rats during perimenopause.
AB  - During perimenopause, oxidative stress increases, which may result in disruption
      of bone turnover, and consequently in osteoporosis. The use of antioxidants may
      be an effective nutritional approach to reducing osteoporosis in this period of
      life. Mate tea (MT) (Ilex paraguariensis), a typical and inexpensive beverage
      consumed in the Brazilian south-east, Argentina and Uruguay, increases
      antioxidant defense. Our hypothesis was that MT would decrease oxidative stress
      and mitigate bone deterioration. To test this, we analyzed oxidative stress
      markers of bone turnover, and local and systemic markers of bone metabolism of
      rats during natural perimenopause. Female Wistar rats (aged 16months) in proven
      perimenopause period received 20mg/kgBW/day of mate tea, by gavage (PM+MT Group,
      n=10) or water (PM Group, n=10). Female rats aged 4months (AD Group, n=10)
      received water. The treatment period was four weeks. MT minimized the
      deterioration of rat microarchitecture, characterized by increase in the bone
      trabecular area, number of osteocytes and areal bone mineral density. These
      results were accompanied by a lower level of malondialdehyde, an oxidative stress
      marker, in femoral tissue homogenate. Plasmatic tartrate-resistant acid
      phosphatase, a typical osteoclastic function marker, decreases after treatment,
      indicating a decrease in osteoclastic function. MT also modified the
      immunostaining pattern of bone metabolism markers, decreasing the receptor
      activator of nuclear factor kappa-B ligant (RANKL), superoxide dismutase isoform
      2 (SOD2) and increasing osteoprotegerin (OPG), a decoy receptor for the RANKL,
      which positively modulates bone mass. These results suggested MT was capable of
      decreasing bone resorption by inhibiting the osteoclastogenesis in a RANKL
      dependent signaling pathway activated by oxidative stress. Taken together, the
      results indicated that MT minimized bone loss in perimenopause and this effect is
      at least partly due to the decrease in oxidative stress, confirming our
      hypothesis.

PMID- 28739430
TI  - Evaluation of MR imaging-targeted biopsies of the prostate in biopsy-naive
      patients. A single centre study.
AB  - PURPOSE: To evaluate the differences in prostate cancer detection rate and biopsy
      effectiveness between magnetic resonance imaging (MRI) target biopsy (TB) and
      transperineal standard biopsy (SB) in biopsy-naive patients. MATERIAL AND
      METHODS: Between October 2014 and April 2016, 60 men with a mean age of 64.1+/
      6.7 (SD) years (range: 53-82 years) were prospectively enrolled. All patients
      underwent a prostate MRI study, evaluated by two radiologists, before undergoing
      the biopsy. A transperineal 12-core SB was carried out before TB, without the
      information from the MRI. The detection rate for all tumors and for clinically
      significant tumors (CS) was recorded. Sampling variables such as the proportion
      of cores positive for CS cancer (PCP-CS) and the maximum cancer core length
      (MCCL) were also calculated. The ability of MRI to predict the presence of a CS
      tumor at biopsy was studied using a sector analysis. Patients with negative
      biopsies were followed during a minimum of 12 months. RESULTS: The detection rate
      for SB and TB was 53.3% (32/60) and 46.7% (28/60) respectively for all tumors
      (P=0.289) and 45% (27/60) in both techniques for CS tumors. TB obtained a larger
      PCP-CS (P<0.001) and MCCL (P=0.018). The sensitivity, specificity, positive
      predictive value, negative predictive value and cancer prevalence was 83.3%,
      92.9%, 83.3%, 92.9% and 30% for peripheral zone sectors and 43.8%, 97.1%, 70.0%,
      91.8% and 13,3% for transitional zone sectors. The proportion of patients that
      showed an increase of PSA faster than 0.75ng/mL/year after a negative biopsy was
      26.1%. CONCLUSION: Detection rate of prostate cancer did not show significant
      differences between a TB and a SB technique in biopsy-naive patients. However,
      targeted prostate biopsies demonstrated a better sampling effectiveness thus
      reducing the cores needed to diagnose clinically significant tumors.

PMID- 28739431
TI  - Protocol optimization of sacroiliac joint MR Imaging at 3 Tesla: Impact of coil
      design and motion resistant sequences on image quality.
AB  - PURPOSE: To evaluate the impact of coil design and motion-resistant sequences on
      the quality of sacroiliac magnetic resonance imaging (MRI) examination in
      patients with spondyloarthropathy. PATIENTS AND METHODS: One hundred and twenty
      one patients with suspected sacroiliitis and referred for MRI of the sacroiliac
      joints were retrospectively evaluated with MRI at 3-Tesla. There were 78 women
      and 43 men with a mean age of 36.7+/-11.5 (SD) years (range: 15.8-78.4 years).
      Conventional and motion-resistant fat-saturated fast-spin echo T2-weighted
      sequences were performed with two different coils. Image quality was subjectively
      evaluated by two independent readers (R1 and R2) using a four-point scale.
      Confidence in the identification of bone marrow edema pattern (BMEP) was also
      evaluated subjectively using a three-point scale. RESULTS: Phased array body coil
      yielded improved image quality compared to surface coil (14.1 to 30.4% for R1 and
      14.6 to 25.7% for R2; P<0.0001). The impact of the sequence type on quality was
      also statistically significant (P=0.0046). BMEP was identified in 40 patients and
      best inter-reader agreement was obtained using the combination of phased-array
      body coil with motion-resistant T2-weighted sequence (kappa 0.990). The smallest
      number of indeterminate BMEP zones was seen on MRI set acquired with the phased
      array body coil and motion-resistant T2-weighted sequence. CONCLUSION: Phased
      array body coil and motion-resistant T2-weighted sequences perform better than
      surface coil and conventional T2-weighted sequences for the evaluation of
      sacroiliac joints, increasing confidence in the identification of BMEP.

PMID- 28739432
TI  - Magnetic resonance enterography with oral mannitol solution: Diagnostic efficacy
      and image quality in Crohn disease.
AB  - PURPOSE: The aim of this study was to investigate the diagnostic efficacy and
      image quality of magnetic resonance enterography (MRE) using oral mannitol
      solution for the evaluation Crohn disease (CD). MATERIALS AND METHODS: We
      retrospectively evaluated MRE examinations of 153 patients with an assumed or
      definitive diagnosis of CD. There were 65 men and 88 women, with a mean age of
      35.7 years (range: 6-73years). MRE findings of the patients were compared to
      histopathologic results obtained by surgery-fiberoptic endoscopy. The
      sensitivity, specificity and diagnostic efficacy rate were calculated.
      Additionally, image quality of MRE was evaluated using a four-point scale
      (1=excellent, 4=poor/non-diagnostic). RESULTS: Sensitivity, specificity and
      diagnostic efficacy were 92.5%, 93% and 92.8%, respectively. Six patients had
      false-positive and five patients had false-negative findings. Three falsely
      positive patients had ulcerative colitis and three had non-specific terminal
      ileitis. A total of 765 small bowel segments were analyzed; 475 (62%) had an
      image quality score of 1 and 15 (2%), an image quality score of 4. CONCLUSION:
      MRE using oral mannitol solution provides excellent image quality for MRE and has
      high degrees of diagnostic efficacy in CD patients.

PMID- 28739433
TI  - Pain management: The rising role of interventional oncology.
AB  - Patients with early or metastatic cancer may suffer from pain of different
      origins. The vast majority of these patients are not adequately treated by means
      of systemic analgesia and radiotherapy. Percutaneous neurolysis is performed
      using chemical agents or thermal energy upon sympathetic nervous system plexus
      for pain reduction and life quality improvement. Ablation and vertebral
      augmentation are included in clinical guidelines for metastatic disease. As far
      as the peripheral skeleton is concerned bone augmentation and stabilization can
      be performed by means of cement injection either solely performed or in
      combination to cannulated screws or other metallic or peek implants. This review
      describes the basic concepts of interventional oncology techniques as therapies
      for cancer pain management. The necessity for a tailored-based approach applying
      different techniques for different cases and locations will be addressed.

PMID- 28739434
TI  - Combined use of postmortem 3D computed tomography reconstructions and 3D-design
      software for postmortem ballistic analysis.

PMID- 28739435
TI  - Ureaplasma spp. in male infertility and its relationship with semen quality and
      seminal plasma components.
AB  - OBJECTIVE: We investigated the prevalence of Ureaplasma spp. in semen samples of
      infertile men in Shanghai, China and evaluated the correlation between the sperm
      parameters (seminal volume, sperm concentration, progressive motility and non
      progressive) and the secretary function in these infectious populations. METHODS:
      Semens were collected from 540 infertile men and 260 fertile control group in
      shanghai, China and subjected to standard bacterial and Ureaplasma spp. culture.
      Positive Ureaplasma spp. isolates were further tested by PCR to detect the
      biovars and serotypes of Ureaplasma spp. Sperm seminological variabilities were
      analyzed by Computer-Assisted Semen Analysis according to the fifth edition of
      World Health Organization (WHO) laboratory manual for the examination and
      processing of human semen. Seminal markers were measured by the automatic
      analyzer. RESULTS: The prevalence of Ureaplasma spp. in semen specimens was 39.6%
      (214/540) and 19.2% (50/260) in infertile and control group, respectively.
      Significant difference was observed between the two groups (P < 0.001). Among all
      clinical isolates from infertile men (n = 214), 59.3% (n = 127) was Ureaplasma
      parvum (UPA), 26.2% (n = 56) was Ureaplasma urealyticum (UUR), and 14.5% (n = 31)
      was mixed species. While those numbers in control group (n = 50) were 64.0% (n =
      32), 20.0% (n = 10), 16.0% (n = 8), respectively. There was no significant
      difference between any two groups (P > 0.05). The progressive motility and the
      NAG activity of infertile men infected with UPA and mixed species were
      significantly lower than those of UUR infected subgroup (P < 0.05). CONCLUSIONS:
      The infection of Ureaplasma spp. plays an important pathogenic role in male
      infertility. UPA has higher pathogenicity on the progressive motility and the
      secretary function of epididymis than UUR.

PMID- 28739436
TI  - Efficacy of isoniazid salvage therapy for latent tuberculosis infection in
      patients with immune-mediated inflammatory disorders - A retrospective cohort
      study in Taiwan.
AB  - BACKGROUND: Active tuberculosis (TB) in patients with latent tuberculosis
      infection (LTBI) was associated with use of biological agents for immune-mediated
      inflammatory disorders (IMIDs). For decreasing active TB, isoniazid prophylaxis
      therapy was administered before biologic therapy among IMID patients with LTBI.
      However, for patients who had been received biologics for a long time with
      unknown status of LTBI or exposure history of active TB, the prevalence of LTBI
      and efficacy of isoniazid therapy were unclear. METHOD: A retrospective cohort
      study was conducted during 2012-2014 in a tertiary medical center in Taiwan, and
      the incidence case of active TB was identified by the national TB registration
      system on October 1, 2015. RESULTS: All 382 patients with 1532 person-years were
      followed up, the initial prevalence of LTBI by positive interferon-gamma
      releasing assay (IGRA+) was 17.5%. The prevalence of LTBI was increased in elder
      age (>20%, p < 0.05), chronic kidney disease (33%, p < 0.05), metabolic syndrome
      (26.3%, p < 0.05), but not related to the type of IMIDs or biologics. The crude
      incidences of TB were increased in elders (53.3/1000 person-year), abnormal chest
      film (49.6/1000 person-year), administration of tocilizumab (13.6/1000 person
      year), and metabolic syndrome (56.1/1000 person-year), respectively. Among
      patents with LTBI, the incidence of active TB was lower in patients with
      isoniazid therapy (9.2/1000 person-year, p = 0.02) than without isoniazid therapy
      (92.2/1000 person-years), regardless the timing of initiating isoniazid therapy
      (p > 0.05). CONCLUSION: Isoniazid therapy can prevent active TB from LTBI despite
      of the timing of biologics administration.

PMID- 28739437
TI  - Short term exercise training enhances cell-mediated responses to HSV-1 vaccine in
      mice.
AB  - Exercise (with appropriate intensity and duration) is a natural modulator of
      immune responses and may be useful to increase the vaccine response towards
      antigen. According to the fact that rural area responding butter than urbon area
      to vaccine protocol, this study was undertaken to test the hypothesis that short
      term exercise training as an adjuvant for antigen such as herpes simplex virus
      type 1 (HSV-1) in animal models. Mice with/without access to short term exercise
      training were immunized intramuscularly with inactivated KOS strain of HSV-1.
      Immune responses was investigated with regards of both cell-mediated and humoral
      immunity. In this study by using short term exercise training as an adjuvant
      enhanced Th1 response while it did not show significant effect on Th2 responses
      towards HSV-1 immunization. Also, immunoglobulin G (IgG) 2a/IgG1-ratios increased
      in vaccine with short term exercise training group. These results suggested that
      coupling short term moderate exercise training as a mild adjuvant with
      vaccination may enhance cell-mediated immune responses especially Th1 responses.

PMID- 28739438
TI  - Pathogenicity of the Egyptian A/H5N1 avian influenza viruses in chickens.
AB  - Long-term circulation of highly pathogenic avian influenza H5N1 viruses of clade
      2.2.1 in Egyptian poultry since February 2006 resulted in the evolution of two
      distinct clades: 2.2.1.1 represents antigenic-drift variants isolated from
      vaccinated poultry and 2.2.1.2 that caused the newest upsurge in birds and humans
      in 2014/2015. In the present study, nine isolates were collected from chickens,
      ducks and turkeys representing the commercial and backyard sectors during the
      period 2009-2015. The subtyping was confirmed by hemagglutination inhibition (HI)
      test, RT-qPCR and sequence analysis. The Mean Death Time (MDT) and Intravenous
      Pathogenicity Index (IVPI) for all isolates were determined. Sequence analysis of
      the HA gene sequences of these viruses revealed that two viruses belonged to
      clade 2.2.1.1 and the rest were clade 2.2.1.2. Antigenic characterisation of the
      viruses supported the results of the phylogenetic analysis. The MDT of the
      isolates ranged from 18 to 72 h and the IVPI values ranged from 2.3 to 2.9;
      viruses of the 2.2.1.1 clade were less virulent than those of the 2.2.1.2 clade.
      In addition, clade-specific polymorphism in the HA cleavage site was observed.
      These findings indicate the high and variable pathogenicity of H5N1 viruses of
      different clades and host-origin in Egypt. The upsurge of outbreaks in poultry in
      2014/2015 was probably not due to a shift in virulence from earlier viruses.

PMID- 28739439
TI  - The association of type II diabetes with gut microbiota composition.
AB  - It is known that type 2 diabetes (T2D) in humans could be linked to the
      composition of gut microbiota. The aim of this study was to evaluate three faecal
      bacterial species, including Bacteroides fragilis, Bifidobacterium longum and
      Faecalibacterium prausnitzii in patients with T2D. This case control study
      included 18 patients with T2D and 18 matched persons without diabetes. The
      concentrations of B. fragilis, B. longum and F. prausnitzii were determined by
      quantitative Real-Time PCR. Quantitative PCR analysis revealed that the gut
      bacterial composition in patients with T2D was partially different from that in
      the healthy individuals. Faecalibacterium prausnitzii was significantly lower in
      patients with T2D (P-value = 0.038). Bacteroides fragilis was under-represented
      in the microbiota of the group with diabetes, but its difference between two
      groups was not significant (P-value = 0.38). No difference was observed for B.
      longum community between the both groups (P-value = 0.99). Characterization of
      specific species of intestinal microbiota shows some compositional changes in
      patients with T2D. The results may be valuable for developing strategies to
      control type 2 diabetes by modifying the intestinal microbiota. Long-term studies
      with emphasis on other bacterial groups are suggested to clarify the association
      of T2D with gut microbiota.

PMID- 28739440
TI  - Genetic Variation in GSTP1, Lung Function, Risk of Lung Cancer, and Mortality.
AB  - INTRODUCTION: Glutathione S-transferase pi 1 metabolizes carcinogens from tobacco
      smoke in the lung. We tested whether genetically altered glutathione S
      transferase pi 1 activity affects lung function and risk for tobacco-related
      cancer and mortality in the general population. METHODS: We genotyped 66,069
      individuals from the white general population for two common functional variants
      in the glutathione S-transferase pi 1 gene (GSTP1)-amino acid isoleucine 105
      changed to a valine (Ile105Val) and amino acid alanine 114 changed to a valine
      (Ala114Val)-and recorded lung function, lung cancer, tobacco-related cancer, and
      death as outcomes. RESULTS: Lung function was increased stepwise with the
      Ile105Val genotype overall (p < 0.01) and among smokers separately (p < 0.01).
      Adjusted hazard ratios for lung cancer, tobacco-related cancer, and death were
      reduced stepwise with the Ile105Val genotype (p < 0.02): Ile105Val homozygotes
      and heterozygotes versus noncarriers had hazard ratios for lung cancer of 0.64
      (0.47-0.89) and 0.93 (0.78-1.11), for tobacco-related cancer of 0.74 (0.60-0.92)
      and 0.92 (0.81-1.04), and hazard ratios for death of 0.87 (0.80-0.95) and 0.94
      (0.89-0.99), respectively. Population prevented fractions of lung cancer, tobacco
      related cancer, and death due to Ile105Val homozygosity were 4%, 3% and 2%,
      respectively. The Ala114Val genotype was associated with reduced mortality (p <
      0.01) but not with lung function, lung cancer, or tobacco-related cancer.
      CONCLUSION: GSTP1 Ile105Val was associated with increased lung function, reduced
      risk for lung cancer and tobacco-related cancer, and reduced all-cause mortality
      in the general population.

PMID- 28739441
TI  - Prognostic Factors in Completely Resected Node-Negative Lung Adenocarcinoma of 3
      cm or Smaller.
AB  - INTRODUCTION: The role of adjuvant chemotherapy for patients with stage I NSCLC
      remains unknown. The prognostic value of histological subtypes in resected node
      negative small lung adenocarcinoma has not been widely investigated. This study
      investigated the prognostic factors in patients with node-negative lung
      adenocarcinoma 3 cm or smaller to find potential candidates for adjuvant
      chemotherapy. METHODS: A total of 726 patients with completely resected node
      negative lung adenocarcinoma 3 cm or smaller were included in the study.
      Prognostic factors for overall survival or probability of freedom from recurrence
      (FFR) were investigated. RESULTS: During follow-up, recurrence developed in 59
      patients (8.1%). Univariate analysis showed that the micropapillary/solid
      predominant pattern group was associated with a significantly lower probability
      of FFR (p = 0.001) in node-negative lung adenocarcinoma 3 cm or smaller. Those
      with greater tumor size (p = 0.001) and the micropapillary/solid predominant
      pattern group (p = 0.035) had a significantly lower probability of FFR in
      multivariate analysis. For tumors 2 cm or smaller, the micropapillary/solid
      predominant pattern group had a trend toward a lower probability of FFR (p =
      0.053) in multivariate analysis. Presence of the solid pattern was a prognostic
      factor for lower probability of FFR (p = 0.001) in multivariate analysis.
      CONCLUSIONS: The new adenocarcinoma classification has significant impact on
      recurrence in node-negative lung adenocarcinoma 3 cm or smaller. Patients with
      the micropapillary/solid predominant pattern have a significantly higher risk for
      recurrence. For tumors 2 cm or smaller, presence of the solid pattern was a
      prognostic factor for higher probability of recurrence. This information is
      useful for patient stratification for adjuvant therapy.

PMID- 28739442
TI  - No effect of hippocampal lesions on stimulus-response bindings.
AB  - The hippocampus is believed to be important for rapid learning of arbitrary
      stimulus-response contingencies, or S-R bindings. In support of this, Schnyer et
      al. (2006) (Experiment 2) measured priming of reaction times (RTs) to categorise
      visual objects, and found that patients with medial temporal lobe damage, unlike
      healthy controls, failed to show evidence of reduced priming when response
      contingencies were reversed between initial and repeated categorisation of
      objects (a signature of S-R bindings). We ran a similar though extended object
      classification task on 6 patients who appear to have selective hippocampal
      lesions, together with 24 age-matched controls. Unlike Schnyer et al. (2006), we
      found that reversing response contingencies abolished priming in both controls
      and patients. Bayes Factors provided no reason to believe that response reversal
      had less effect on patients than controls. We therefore conclude that it is
      unlikely that the hippocampus is needed for S-R bindings.

PMID- 28739443
TI  - Sauna exposure immediately prior to short-term heat acclimation accelerates
      phenotypic adaptation in females.
AB  - OBJECTIVES: Investigate whether a sauna exposure prior to short-term heat
      acclimation (HA) accelerates phenotypic adaptation in females. DESIGN:
      Randomised, repeated measures, cross-over trial. METHODS: Nine females performed
      two 5-d HA interventions (controlled hyperthermia Tre>=38.5 degrees C), separated
      by 7-wk, during the follicular phase of the menstrual cycle confirmed by plasma
      concentrations of 17-beta estradiol and progesterone. Prior to each 90-min HA
      session participants sat for 20-min in either a temperate environment (20 degrees
      C, 40% RH; HAtemp) wearing shorts and sports bra or a hot environment (50 degrees
      C, 30% RH) wearing a sauna suit to replicate sauna conditions (HAsauna).
      Participants performed a running heat tolerance test (RHTT) 24-h pre and 24-h
      post HA. RESULTS: Mean heart rate (HR) (85+/-4 vs. 68+/-5 bpm, p<=0.001), sweat
      rate (0.4+/-0.2 vs. 0.0+/-0.0Lh-1, p<=0.001), and thermal sensation (6+/-0 vs.
      5+/-1, p=0.050) were higher during the sauna compared to temperate exposure.
      Resting rectal temperature (Tre) (-0.28+/-0.16 degrees C), peak Tre (-0.42+/-0.22
      degrees C), resting HR (-10+/-4 bpm), peak HR (-12+/-7 bpm), Tre at sweating
      onset (-0.29+/-0.17 degrees C) (p<=0.001), thermal sensation (-0.5+/-0.5;
      p=0.002), and perceived exertion (-3+/-2; p<=0.001) reduced during the RHTT,
      following HAsauna; but not HAtemp. Plasma volume expansion was greater following
      HAsauna (HAsauna, 9+/-7%; HAtemp, 1+/-5%; p=0.013). Sweat rate (p<=0.001)
      increased and sweat NaCl (p=0.006) reduced during the RHTT following HAsauna and
      HAtemp. CONCLUSIONS: This novel strategy initiated HA with an attenuation of
      thermoregulatory, cardiovascular, and perceptual strain in females due to a
      measurably greater strain in the sauna compared to temperate exposure when
      adopted prior to STHA.

PMID- 28739444
TI  - Small molecule therapeutics for inflammation-associated chronic musculoskeletal
      degenerative diseases: Past, present and future.
AB  - Inflammation-associated chronic musculoskeletal degenerative diseases (ICMDDs)
      like osteoarthritis and tendinopathy often results in morbidity and disability,
      with consequent heavy socio-economic burden. Current available therapies such as
      NSAIDs and glucocorticoid are palliative rather than disease-modifying.
      Insufficient systematic research data on disease molecular mechanism also makes
      it difficult to exploit valid therapeutic targets. Small molecules are designed
      to act on specific signaling pathways and/or mechanisms of cellular physiology
      and function, and have gradually shown potential for treating ICMDDs. In this
      review, we would examine and analyze recent developments in small molecule drugs
      for ICMDDs, suggest possible feasible improvements in treatment modalities, and
      discuss future research directions.

PMID- 28739445
TI  - Surface charge dependent separation of modified and hybrid ferritin in native
      PAGE: Impact of lysine 104.
AB  - : Preparation of modified and hybrid ferritin provides a great opportunity to
      understand the mechanisms of iron loading/unloading, protein self-assembly, size
      constrained nanomaterial synthesis and targeted drug delivery. However, the large
      size (M.W.=490kDa) has been limiting the separation of different modified and/or
      hybrid ferritin nanocages from each other in their intact assembled form and
      further characterization. Native polyacrylamide gel electrophoresis (PAGE)
      separates proteins on the basis of both charge and mass, while maintaining their
      overall native structure and activity. Altering surface charge distribution by
      substitution of amino acid residues located at the external surface of ferritin
      (K104E & D40A) affected the migration rate in native PAGE while internal
      modification had little effect. Crystal structures confirmed that ferritin
      nanocages made up of subunits with single amino acid substitutions retain the
      overall structure of ferritin nanocage. Taking advantage of K104E migration
      behavior, formation of hybrid ferritins with subunits of wild type (WT) and K104E
      were confirmed and separated in native PAGE. Cage integrity and iron loading
      ability (ferritin activity) were also tested. The migration pattern of hybrid
      ferritins in native PAGE depends on the subunit ratio (WT: K104E) in the ferritin
      cage. Our work shows that native PAGE can be exploited in nanobiotechnology, by
      analyzing modifications of large proteins like ferritin. SIGNIFICANCE: Native
      PAGE, a simple, straight-forward technique, can be used to analyze small
      modification (by altering external surface charge) in large proteins like
      ferritin, without disintegrating its self-assembled nanocage structure. In doing
      so, native PAGE can complement the information obtained from mass spectrometry.
      The confirmation and separation of modified and hybrid ferritin protein nanocages
      in native PAGE, opens up various prospects of bio-conjugation, which can be
      useful in targeted drug delivery, nanobiotechnology and in understanding nature's
      idea of synthesizing hybrid ferritins in different human tissues.

PMID- 28739446
TI  - Crystallographic insights into a cobalt (III) sepulchrate based alternative
      cofactor system of P450 BM3 monooxygenase.
AB  - P450 BM3 is a multi-domain heme-containing soluble bacterial monooxygenase. P450
      BM3 and variants are known to oxidize structurally diverse substrates. Crystal
      structures of individual domains of P450 BM3 are available. However, the spatial
      organization of the full-length protein is unknown. In this study, crystal
      structures of the P450 BM3 M7 heme domain variant with and without cobalt (III)
      sepulchrate are reported. Cobalt (III) sepulchrate acts as an electron shuttle in
      an alternative cofactor system employing zinc dust as the electron source. The
      crystal structure shows a binding site for the mediator cobalt (III) sepulchrate
      at the entrance of the substrate access channel. The mediator occupies an unusual
      position which is far from the active site and distinct from the binding of the
      natural redox partner (FAD/NADPH binding domain).

PMID- 28739447
TI  - Laparoscopic resection of interaortocaval paraganglioma in left lateral decubitus
      (with video).

PMID- 28739448
TI  - Hydrocortisone and Ascorbic Acid Synergistically Prevent and Repair
      Lipopolysaccharide-Induced Pulmonary Endothelial Barrier Dysfunction.
AB  - BACKGROUND: Sepsis refers to the dysregulated host immune response elicited by
      microbial infections resulting in life-threatening organ dysfunction. Sepsis
      represents a medical challenge, since it is associated with a rate of death as
      high as 60%. Septic shock is strongly associated with vascular dysfunction and
      elevated pulmonary capillary permeability. We recently reported that the
      combination of hydrocortisone (HC), ascorbic acid (vitC), and thiamine
      dramatically improves outcomes and reduces mortality in patients with sepsis. In
      the present study, we provide experimental evidence in support of the hypothesis
      that the combination of HC and vitC enhances endothelial barrier function.
      METHODS: Human lung microvascular endothelial cells were exposed to
      lipopolysaccharide (LPS) in the absence or presence of HC and vitC. RESULTS: LPS
      alone induced profound hyperpermeability, as reflected in decreased values of
      transendothelial electrical resistance. vitC alone did not exhibit barrier
      enhancement properties nor did it affect the LPS-induced hyperpermeability.
      Similarly, HC alone exhibited only a minor barrier-enhancing and protective
      effect. Conversely, the combination of HC and vitC, either as before or after
      treatment, dramatically reversed the LPS-induced barrier dysfunction. The barrier
      protective effects of HC and vitC were associated with reversal of LPS-induced
      p53 and phosphorylated cofilin downregulation and LPS-induced RhoA activation and
      myosin light chain phosphorylation. CONCLUSIONS: These data provide a novel
      mechanism of endothelial barrier protection and suggest one possible pathway that
      may contribute to the therapeutic effects of HC and vitC in patients with sepsis.

PMID- 28739449
TI  - Strategies to enhance the distribution of nanotherapeutics in the brain.
AB  - Convection enhanced delivery (CED) provides a powerful means to bypass the blood
      brain barrier and drive widespread distribution of therapeutics in brain
      parenchyma away from the point of local administration. However, recent studies
      have detailed that the overall distribution of therapeutic nanoparticles (NP)
      following CED remains poor due to tissue inhomogeneity and anatomical barriers
      present in the brain, which has limited its translational applicability. Using
      probe NP, we first demonstrate that a significantly improved brain distribution
      is achieved by infusing small, non-adhesive NP via CED in a hyperosmolar infusate
      solution. This multimodal delivery strategy minimizes the hindrance of NP
      diffusion imposed by the brain extracellular matrix and reduces NP confinement
      within the perivascular spaces. We further recapitulate the distributions
      achieved by CED of this probe NP using a most widely explored biodegradable
      polymer-based drug delivery NP. These findings provide a strategy to overcome
      several key limitations of CED that have been previously observed in clinical
      trials.

PMID- 28739450
TI  - Controlled release for crop and wood protection: Recent progress toward
      sustainable and safe nanostructured biocidal systems.
AB  - We review biocide delivery systems (BDS), which are designed to deter or control
      harmful organisms that damage agricultural crops, forests and forest products.
      This is a timely topic, given the growing socio-economical concerns that have
      motivated major developments in sustainable BDS. Associated designs aim at
      improving or replacing traditional systems, which often consist of biocides with
      extreme behavior as far as their solubility in water. This includes those that
      compromise or pollute soil and water (highly soluble or volatile biocides) or
      those that present low bioavailability (poorly soluble biocides). Major
      breakthroughs are sought to mitigate or eliminate consequential environmental and
      health impacts in agriculture and silviculture. Here, we consider the most
      important BDS vehicles or carriers, their synthesis, the environmental impact of
      their constituents and interactions with the active components together with the
      factors that affect their rates of release such as environmental factors and
      interaction of BDS with the crops or forest products. We put in perspective the
      state-of-the-art nanostructured carriers for controlled release, which need to
      address many of the challenges that exist in the application of BDS.

PMID- 28739451
TI  - Rescue of a Failing Endovascular Infrarenal Aortic Repair Using an Off-The-Shelf
      Branched Endograft.
AB  - BACKGROUND: Proximal aortic dilation following open and endovascular aortic
      repair (EVAR) is a well-known phenomenon. If severe enough, it may lead to late
      onset of type Ia endoleak that jeopardizes the proximal seal. METHODS: We report
      the case of a patient previously treated by EVAR for an infrarenal aneurysm who
      developed a type Ia endoleak after proximal aortic dilation. His aneurysms
      enlarged to 10 cm mandating a rapid repair without the delay for a custom-made
      device. RESULTS: We successfully used the off-the-shelf thoracic t-Branch graft
      (Cook, Bloomington, IN) with its 4 branches to treat the dilated aorta and seal
      the endoleak. CONCLUSION: The off-the-shelf t-Branch is a useful option in
      patient with previous EVAR presenting with proximal aortic dilation and endoleak
      who cannot wait for a custom-made device.

PMID- 28739452
TI  - "Over-SIRIX": A New Method for Sizing Aortic Endografts in Combination with the
      Chimney Grafts: Early Experience with Aortic Arch Disease.
AB  - BACKGROUND: Large gutters after chimney procedures are one of the main causes of
      type I endoleak (EL-I). This study aims to evaluate a new tailored planning named
      "Over-SIRIX," based on Osirix Imaging Software, to choose the correct main graft
      oversizing in order to minimize EL-I incidence. METHODS: From 2008 to 2015, 34
      patients were treated with parallel grafts for aortic arch diseases at our
      institution. The study included 22 patients with single stent and antegrade flow
      configuration; they were divided into 2 groups (PRE- and POST-"Over-SIRIX").
      "Over-SIRIX" was carried out in the retrospective group (PRE-"Over-SIRIX"), and
      it was used to plan the endovascular procedure in the prospective group (POST
      "Over-SIRIX"). Through the multiplanar reconstruction (MPR) of the preoperative
      computed tomography angiography (CTA), the proximal neck of the chimney grafts
      was studied. Stent and endograft configurations were drawn in order to minimize
      the "gutters." To obtain the ideal main graft sizing (I-Size), a formula was used
      by adding the custom sizing (C-Size) to the disease oversizing (D-Over). The same
      MPR imaging was evaluated on postoperative CTA to study gutters area and presence
      of EL-I. RESULTS: The mean I-Size was 41.67 mm that was equivalent to an ideal
      oversizing of 19.3% (range 10-28%). The gutters area decreased from 7.3 to 1.7
      mm2 (PRE/POST) and EL-I rate from 28.5% to 0% (PRE/POST). Gutters area bigger
      than 7.5 mm2 and planning made without "Over-SIRIX" were significantly associated
      (P < 0.05) to EL-I. CONCLUSIONS: "Over-SIRIX" appears to be a feasible method to
      customize planning during chimney technique, reducing the risk of EL-I which is
      significantly related to the presence and size of the gutters.

PMID- 28739453
TI  - Modified Frailty Index Can Be Used to Predict Adverse Outcomes and Mortality
      after Lower Extremity Bypass Surgery.
AB  - BACKGROUND: Frailty has been increasingly used as a prognostic indicator for
      various surgical operations. Patients with peripheral arterial disease represent
      a cohort of population with advanced medical comorbidities. The aim of this study
      is to correlate the postoperative outcomes after lower extremity bypass surgery
      with preoperative modified frailty index (mFI). METHODS: Using 2010 American
      College of Surgeons National Surgical Quality Improvement Program database,
      patients undergoing infrainguinal arterial bypass surgery were identified. mFI
      with 11 variables, based on the Canadian Study of Health and Aging Frailty Index,
      was utilized. Based on mFI score, the patients were divided into 4 groups: group
      1 (mFI score: 0-0.09), group 2 (mFI score: 0.18-0.27), group 3 (mFI score: 0.36
      0.45), and group 4 (mFI score: 0.54-0.63). A bivariate and multivariate analysis
      was done using logistic regression analysis. RESULTS: A total of 4,704 patients
      (64% males and 36% females) underwent infrainguinal arterial bypass. Mean age was
      67.9 +/- 11.7 years. Distribution of patients based on mFI was as follows: group
      1: 14.6%, group 2: 55.9%, group 3: 26.9%, and group 4: 2.6%. Increase in mFI was
      associated with higher mortality rates. Incidence of mortality for group 1 was
      0.6%; for group 2, it was 1.4%; for group 3, it was 4%; and for group 4, it was
      7.4%. Likewise, the incidence of other postoperative complications such as
      myocardial infarction (MI), stroke, progressive renal failure, and graft failure
      was significantly high among patients with high mFI scores. Following factors
      were associated with increased risk of mortality: high mFI score, black race,
      dialysis dependency, postoperative renal insufficiency, MI, and postoperative
      acute renal failure. CONCLUSIONS: This study demonstrates that the mFI can be
      used as a valuable tool to identify patients at a higher risk for developing
      postoperative complications after lower extremity revascularization. For patients
      with mFI score of 0.54-0.63, the risk of mortality and complications increases
      significantly. mFI can be used as a useful screening tool to identify patients
      who are at a high risk for developing complications.

PMID- 28739454
TI  - Parallel Grafts Used in Combination with Physician-Modified Fenestrated Stent
      Grafts for Complex Aortic Aneurysms in High-risk Patients with Hostile Anatomies.
AB  - BACKGROUND: The objective of the study was to evaluate the feasibility and early
      outcomes of complex aortic aneurysm repair in high-risk patients with hostile
      anatomies using both parallel stents and physician-modified stent graft (PMSG)
      techniques to address the renovisceral arteries. METHODS: Consecutive patients
      with complex suprarenal (SRA) and thoracoabdominal aortic aneurysms (TAAAs)
      undergoing endovascular repair using combined parallel stents technique and PMSG
      between September 2013 and November 2015 were evaluated. All patients required
      prompt aneurysm treatment. Fenestrations to preserve branch vessels were created
      in thoracic stent grafts. Depending on the anatomy, chimney or snorkel stents
      were deployed in renal or visceral arteries as complementary technique to
      overcome severe angulations or preexisting suprarenal stent. Preoperative,
      intraoperative, and postoperative data were recorded by means of a prospectively
      maintained database. RESULTS: Six high-risk patients with TAAA (type I: n = 2,
      type III: n = 1) and SRA (n = 3) underwent endovascular repair using both
      parallel stents technique and PMSG. Indications were painful aneurysms (n = 1)
      and >70-mm rapidly enlarging aneurysms (n = 5). Ten thoracic components were
      used, of which 6 were modified intraoperatively. Twenty-one renovisceral arteries
      were revascularized, using dedicated fenestrations (n = 10, 47.7%), chimney (n =
      7, 33.3%), and snorkel stents (n = 4, 19%). The mean operative time was 326 +/-
      82 min including the device modification time. The mean time for graft
      modification was 90 +/- 15 min. In 1 patient, a rescue chimney stent intended to
      the superior mesenteric artery was deployed because of failed cannulation through
      the dedicated fenestration. Technical success rate was 83.3%. One patient died
      during the early postoperative course from severe stroke. Among surviving
      patients, 3 required early reinterventions for iliac occluder-related type II
      endoleak (n = 1), type Ia endoleak (n = 1), and gastroduodenal artery
      embolization (n = 1). The mean follow-up was 14.2 +/- 4.8 months. One early
      gutter-related type I endoleak resolved during follow-up. No other complications
      occurred, and all target vessels remained patent. CONCLUSIONS: PMSG combined with
      parallel stent provided acceptable short-term results in specific presentation of
      SRA and TAAA with hostile anatomies in selected high-risk patients with
      contraindication for standard fenestrated/branched grafts. More reliable outcomes
      require larger population and follow-up.

PMID- 28739455
TI  - Decision-Making in Critical Limb Ischemia: A Markov Simulation.
AB  - BACKGROUND: Critical limb ischemia (CLI) is a feared complication of peripheral
      vascular disease that often requires surgical management and may require
      amputation of the affected limb. We developed a decision model to inform clinical
      management for a 63-year-old woman with CLI and multiple medical comorbidities,
      including advanced heart failure and diabetes. METHODS: We developed a Markov
      decision model to evaluate 4 strategies: amputation, surgical bypass,
      endovascular therapy (e.g. stent or revascularization), and medical management.
      We measured the impact of parameter uncertainty using 1-way, 2-way, and multiway
      sensitivity analyses. RESULTS: In the base case, endovascular therapy yielded
      similar discounted quality-adjusted life months (26.50 QALMs) compared with
      surgical bypass (26.34 QALMs). Both endovascular and surgical therapies were
      superior to amputation (18.83 QALMs) and medical management (11.08 QALMs). This
      finding was robust to a wide range of periprocedural mortality weights and was
      most sensitive to long-term mortality associated with endovascular and surgical
      therapies. Utility weights were not stratified by patient comorbidities;
      nonetheless, our conclusion was robust to a range of utility weight values.
      CONCLUSIONS: For a patient with CLI, endovascular therapy and surgical bypass
      provided comparable clinical outcomes. However, this finding was sensitive to
      long-term mortality rates associated with each procedure. Both endovascular and
      surgical therapies were superior to amputation or medical management in a range
      of scenarios.

PMID- 28739456
TI  - Acute Type B Dissection Causing Collapse of EVAR Endograft and Iliac Limb
      Occlusion.
AB  - We describe a rare case of acute type B dissection (ATBDs) causing collapse of a
      previously placed infrarenal stent graft, resulting in acute limb ischemia due to
      left iliac limb thrombosis in a 59-year-old male. The patient presented with
      acute back and abdominal discomfort radiating to his back, bilateral buttock
      stabbing discomfort and left > right thigh and calf rest pain. CT angiography
      showed a spiral type B dissection with collapse of the proximal portion of the
      endovascular repair of aortic aneurysm (EVAR) device and left limb occlusion.
      Urgent treatment with thoracic endovascular aortic repair distal to the left
      subclavian covered the entry tear and redirected the majority of the flow to the
      true lumen leading to near immediate expansion of the proximal portion of the
      EVAR device. After surgical femoral control, balloon embolectomy of the occluded
      iliac limb was performed and the limb relined. His lower extremity ischemic
      symptoms resolved, and his abdominal and back pain dissipated. At latest 6-month
      follow-up, CT angiography shows an intact thoracic endovascular aortic repair
      stent graft and a widely patent EVAR stent graft, and the patient has no further
      abdominal, back, or leg symptoms. ATBD causing proximal abdominal EVAR collapse
      is an extremely rare presentation of false lumen pressurization and can be
      treated similarly to complicated type B dissection with the goal of restoring
      true lumen patency.

PMID- 28739457
TI  - Distal Ulnar Artery Aneurysm Repair by End-to-End Technique: A Case Report.
AB  - We report the case of a 33-year-old man presented with a posttraumatic 20-mm left
      ulnar artery aneurysm without intraluminal thrombus in the left hypothenar
      eminence. The patient reported left hand paresthesia. Because of symptoms and the
      embolic risk, we decide to plan an aneurysm resection and an interposition graft
      with inverted basilic vein for adequacy diameter (~2 mm), but an end-to-end
      anastomosis was performed instead. We think that the posttraumatic distal artery
      aneurysm could be treated without a bypass but, after a meticulous anatomic
      dissection, with a microvascular anastomosis between the artery stumps.

PMID- 28739458
TI  - Effects of Chemotherapy in Patients with Concomitant Aortic Aneurysm and
      Malignant Disease.
AB  - BACKGROUND: The aim of the study is to present the results in a consecutive
      series of patients affected by aortic abdominal aneurysm and to underline the
      aneurysmal growth and evolution in oncological patients submitted to dedicated
      oncological medical therapy. METHODS: Between January 2010 and June 2016 we
      treated in our center 19 patients for coexisting aortic aneurysms (>3 cm) and
      malignancy. We observed patients undergoing oncological treatment and patients
      who did not undergo medical treatment. We studied computed tomography (CT) scan
      at the time when patients were addressed at our follow-up or treatment and we
      analyzed retrospectively prior CT scan at 6 and 12 months. RESULTS: Among those
      19 patients, 7 patients were affected by colorectal cancer (36.8%), 6 by urinary
      tract cancer (31.6%), 4 by lymphoma (21%), and 2 by lung cancer (10.6%). In 8
      patients who did not undergo oncological therapy, we did not observe any aortic
      growth; instead, in other 4 patients who underwent oncological medical therapy (3
      abdominal aortic aneurysms and 1 thoracic aneurysm), we observed a mean sac
      growth of 2.9 cm in 6 months with 2 cases of aortic rupture treated in urgent
      fashion. The treatment was open surgery in 2 cases and endovascular in other
      cases. CONCLUSIONS: We observed that oncological drugs may play a role in
      aneurysm growth. Few case reports are found in the literature and more evidences
      are to be found. Those information may influence intention-to-treat small
      aneurysms in short life expectancy patients.

PMID- 28739459
TI  - Comparison of Direct and Less Invasive Techniques for the Treatment of Severe
      Aorto-Iliac Occlusive Disease.
AB  - BACKGROUND: Severe aorto-iliac occlusive disease (AIOD) is traditionally treated
      with aorto-bifemoral bypass (ABF) or aorto-unifemoral bypass (AUF). However,
      cross-femoral bypass (CFB) and hybrid femoral endarterectomy and patch
      angioplasty with iliac stenting (EPS) have gained popularity as less invasive
      options. We sought to compare 1-year survival, primary patency, and major
      amputation rates between open surgical (ABF and AUF) and 2 less invasive
      reconstruction techniques (CFB and EPS) using a large, multicenter cohort. STUDY
      DESIGN: This is a retrospective cohort study of patients who underwent either
      ABF/AUF or CFB/EPS for AIOD between 2006 and 2013 in the Society for Vascular
      Surgery Vascular Quality Initiative registry. Baseline patient and periprocedural
      variables were compared. Propensity score matching (PSM) was performed to predict
      the likelihood of more invasive repair. Kaplan-Meier analysis and Cox models were
      performed for 1-year survival, primary patency, and major amputation. RESULTS:
      1872 patients underwent procedures for AIOD, including 1,133 ABF/AUF and 739
      CFB/EPS, during the study period. Indication was critical limb ischemia in 47.3%
      (n = 886). Median follow-up time was 305 days (range, 10-406). After PSM, the
      matched cohort included 1,094 ABF/AUF and 711 CFB/EPS patients. Multivariate
      analysis revealed that patient factors and procedure indication were significant
      predictors of 1-year mortality and major amputation, but not procedure type.
      ABF/AUF was associated with improved primary patency over CFB/EPS at 1 year
      (94.1% +/- 1.1% vs. 92.3% +/- 1.5%, hazard ratio 0.65, 95% confidence interval
      0.45-0.94; P = 0.02). CONCLUSIONS: In a propensity-matched cohort from a
      multicenter vascular surgery registry, a direct approach to AIOD (ABF/AUF)
      demonstrated better 1-year primary patency than commonly used less invasive
      strategies. However, treatment approach was not a predictor of 1-year survival or
      limb salvage, suggesting that patient factors and procedure indication have a
      greater impact on outcome.

PMID- 28739460
TI  - Rheolytic Thrombectomy with AngioJet(r) Is Safe and Effective in
      Revascularization of Renal Arteries' Acute Occlusion on Previous Complex Aortic
      Endovascular Repair.
AB  - Acute occlusion of the visceral arteries is a threatening complication following
      branched endovascular aortic repair (EVAR). Its prompt diagnosis and treatment
      are mandatory to restore renal function. Several techniques have been used to
      manage this complication. We report 2 clinical cases of patients, previously
      treated with implantation of an off-the-shelf thoracoabdominal aortic endograft,
      with acute bilateral occlusion of the renal arteries. Both patients were
      successfully treated with AngioJet rheolytic thrombectomy. Acute occlusion of the
      renal arteries can dramatically complicate the outcome of patients treated with
      branched EVAR. Prompt diagnosis and treatment are required. Rheolytic
      thrombectomy rapidly removes intra-arterial thrombus through Bernoulli effect,
      preventing the risk of distal embolization and rapidly restoring the renal
      function.

PMID- 28739461
TI  - Perforator Vein Access for Venous Pharmacomechanical Thrombolysis.
AB  - A 28-year-old Hispanic female with a history of deep vein thrombosis (DVT)
      presented to the emergency room with left lower extremity swelling and pain. On
      duplex venous examination, an extensive left lower extremity DVT extending to her
      left common iliac vein was identified. A perforator vein measuring 2.6 mm located
      in the midcalf area was used to access and perform mechanical and chemical
      thrombolysis. Complete resolution of symptoms was observed.

PMID- 28739462
TI  - Suprageniculate Approach to Release of Popliteal Entrapment without Distal Bypass
      Despite Preoperative Runoff Thrombosis.
AB  - BACKGROUND: Popliteal artery entrapment syndrome is an uncommon condition in
      which anatomic or functional popliteal artery compression causes arterial
      insufficiency. We present a case of popliteal entrapment with runoff thrombosis
      treated with suprageniculate release of entrapment without distal bypass.
      RESULTS: A 15-year old boy with Klinefelter syndrome presented with right leg
      claudication severely limiting his activity. He had a palpable femoral pulse, but
      no palpable popliteal or foot pulses on the right. Noninvasive testing showed a
      partially thrombosed popliteal artery with an ankle-brachial index (ABI) of 0.69.
      Computed tomography scan revealed type III popliteal entrapment with distal
      thromboses and abnormal insertion of gastrocnemius muscle. Popliteal entrapment
      release was performed via a medial suprageniculate approach in consideration for
      distal bypass. The soleus was released first; intraoperative angiography showed
      continued popliteal compression with forced dorsiflexion. This was followed by
      release of the gastrocnemius and found caudal and medial to the soleus as a tight
      band. Repeat angiography showed cessation of popliteal artery compression with
      dorsiflexion. Bypass was not performed due to improvement of distal flow seen on
      angiography. Postoperative recovery was unremarkable. On 1-month and 9-month
      follow-up, he had a normal ABI and arterial duplex, was asymptomatic, and had
      returned to normal activities. CONCLUSIONS: We describe suprageniculate approach
      to popliteal release that may be useful if a distal bypass is planned. In this
      case, bypass was unnecessary despite the abnormal appearance of distal runoff on
      preoperative imaging, as the child's perfusion improved with entrapment release
      alone, and arterial remodeling over time resulted in normal perfusion and
      arterial appearance on duplex imaging.

PMID- 28739463
TI  - Mesoatrial Shunt for Budd-Chiari Syndrome.
AB  - BACKGROUND: The long-term efficacy of mesoatrial shunt (MAS) for Budd-Chiari
      syndrome (BCS) is not well studied. The purpose of our study was to investigate
      the long-term outcome and efficacy of MAS for BCS. METHODS: We retrospectively
      evaluated 11 patients who underwent MAS for BCS from April 1986 to November 1995.
      Records of patients' clinical presentations, laboratorial investigation, Doppler
      duplex ultrasonography, radiologic image, and treatment outcomes were all
      retrieved and analyzed. RESULTS: Follow-up intervals ranged from 1 year and 2
      months to 30 years and 2 months (mean, 17 years and 8 months). Portal pressure
      decreased significantly from 35.72 +/- 3.52 cm H2O to 27.86 +/- 5.83 cm H2O post
      MAS (P = 0.001). The 5-year, 10-year, and 20-year patency were 72.7%, 54.5%,
      36.4%, respectively; 63.3% of patients had survived for more than 10 years and
      45.5% for more than 20 years. A male has been alive with patent shunt for 28
      years and 1 month. CONCLUSIONS: The MAS with enforced rings is an effective
      therapeutic modality for BCS with cautious perioperative management.

PMID- 28739464
TI  - Prophylactic Groin Wound Vacuum-assisted Therapy in Vascular Surgery Patients at
      Enhanced Risk for Postoperative Wound Infection.
AB  - BACKGROUND: Vascular groin wounds have higher than expected surgical site
      infection (SSI) rates and some patients are at enhanced risk. The Wiseman et al.
      paper suggests an objective scoring system that identifies patients at enhanced
      risk of postdischarge SSI. We hypothesize that prophylactic groin wound vacuum
      assisted closure (VAC) therapy in enhanced risk patients will decrease SSI and
      readmission and the Wiseman model provides potential evidence that enhanced risk
      patients can be objectively identified. METHODS: A single institution,
      retrospective analysis was conducted from January 2013 to September 2016
      utilizing procedure codes to identify patients with wound VACs placed in the
      operating room. Two distinct groups were identified. The first was a wound
      complication patient group with 15 limbs (13 patients) with a groin wound VAC
      placed within 45 days postoperatively for groin wound complications. Eleven of
      these limbs had the VAC placed at readmission. The second group was a
      prophylactic patient group that included 8 limbs (7 patients) who received a VAC
      prophylactically placed in the enhanced risk wounds. These wounds were determined
      to be enhanced risk based on clinical criteria judged by the operating surgeon
      such as a large overhanging panniculus and/or one of several ongoing medical
      issues. We calculated a Wiseman score for all patients, determined total cost of
      the readmissions, and determined 30-day postsurgical SSI incidence for the
      prophylactic VAC group. RESULTS: Per the Wiseman scores, 9 limbs with
      postoperative complications were high risk and 3 limbs were moderate/high risk.
      Eleven limbs had a VAC placed at readmission with an average readmission cost of
      $8876.77. For the prophylactic group, 8 limbs were high risk with no observed
      postdischarge SSI in the first 30 days from surgery. The Wiseman scores showed
      close correlation between the retrospective high and moderate/high risk groups
      versus the prophylactic VAC group (31.5 +/- 7.3 vs. 32 +/- 5.5, P = 0.87).
      CONCLUSIONS: The Wiseman scores showed objective validation in the prognosis of
      anticipating groin wound breakdown. Our initial results suggest that prophylactic
      groin wound VAC placement for enhanced risk vascular surgery patients may
      proactively decrease wound morbidity, decrease readmission secondary to groin
      wound complications, and provide some cost benefit.

PMID- 28739465
TI  - Endovascular Treatment of a Renocaval Arteriovenous Fistula Induced Inferior Vena
      Cava Aneurysm.
AB  - Caval aneurysms are very rare but potentially lethal. Discussion about the need
      for treatment rises on individual basis. Based on the underlying etiology, a well
      considered treatment plan should be made. Possible complications for invasive
      treatment and conservative management should be carefully weighed against each
      other. We present a patient with a caval aneurysm due to an arteriovenous fistula
      which we treated with endovascular embolization. Six months after treatment the
      patient is asymptomatic and the aneurysm size is decreased.

PMID- 28739466
TI  - Total Endovascular Treatment of Acute Non-A-non-B Dissection Complicated by
      Visceral Malperfusion without Primary Entry Tear Coverage.
AB  - Management of visceral ischemia due to non-A, non-B dissection is extremely
      challenging due to the position of the primary entry tear at the level of the
      brachiocephalic vessels. We report on a patient who was admitted for a
      complicated non-A, non-B-type dissection with visceral and leg ischemia. A
      covered stent graft was implanted below the primary entry tear to redirect the
      flow in the true lumen, associated with stents implantation in the visceral
      arteries, to treat the dissection's static component. The patient did well,
      without need for bowel resection visceral or late stent restenosis. Stent-graft
      implantation below the primary entry tear in cases of visceral ischemia due to
      non-A, non-B dissection seems feasible.

PMID- 28739467
TI  - Epidemiology and Outcomes of Abdominal Aortic Aneurysms in New Zealand: A 15-Year
      Experience at a Regional Hospital.
AB  - INTRODUCTION: Abdominal aortic aneurysms (AAA) account for approximately 400
      deaths per year in New Zealand (NZ). Waikato Hospital caters to a diverse
      population comprising a high proportion of the indigenous Maori ethnic group
      considered to be at higher risk of mortality and morbidity. Despite these
      population factors, there is no screening program for AAA. The aim of this study
      was to further define the epidemiology and outcomes of AAA repairs in NZ to
      investigate the utility of implementing a population-specific screening program.
      METHODS: A retrospective study of all AAA repairs at Waikato Hospital between
      July 1996 and November 2010 was performed comparing long-term outcomes between
      Europeans and Maori considering acuity of presentation, age, gender, and type of
      repair. Perioperative and overall mortality data were obtained to generate Kaplan
      Meier survival curves. RESULTS: 1,036 AAA repairs were performed. Maori presented
      younger (69.1 vs. 74.5, P < 0.001), had lower male predominance (1.6:1 vs. 3.5:1,
      P < 0.001), less elective repairs (44% vs. 67%, P < 0.001), and more ruptured AAA
      (RAAA) (40% vs. 21%, P < 0.001) despite the overall incidence of RAAA decreasing
      from 26% to 7.8% (P = 0.01). Maori had a lower postoperative 10-year survival
      compared to Europeans (17.4% vs. 36.5%, P < 0.001). There was an initial survival
      benefit for endoluminal over open repair but this converged at 4.9 years post
      repair. CONCLUSIONS: This study highlights the epidemiological trends and
      survival outcomes of AAA management in Maori and Europeans over 15 years. It
      provides further evidence supporting the consideration of a population-specific
      screening program in future.

PMID- 28739468
TI  - Back-Table Surgeon Modification of a t-Branch.
AB  - BACKGROUND: Surgeon modification of commercially available aortic stent grafts
      represents a salvage option to treat complex aortic pathologies in high-risk
      patients. TECHNIQUE: A 68-year-old male was referred to our hospital with a
      contained rupture of the visceral aorta. The patient was previously treated with
      an infrarenal tube graft 16 years earlier as well as with a Crawford procedure
      with island patch of the celiac trunk (TC) and the superior mesenteric artery
      (SMA) and bypasses to both renal arteries 6 years before admission. The computed
      tomography demonstrated a "blowout aneurysm" of the TC and SMA patch. The bypass
      to the left renal artery originated from the level of the TC. We therefore
      modified a commercially available t-branch (Cook(r) Medical, Bloomington, IN)
      with surgeon-made fenestrations for both renal arteries. The procedure was
      successful, and the patient could be discharged to home on the seventh
      postoperative day. CONCLUSIONS: The use of surgeon-modified "off-the-shelf" t
      branches broadens the possibilities of treating even anatomically very
      challenging aortic pathologies otherwise not suitable for the t-branch.

PMID- 28739469
TI  - Acute Venous Iliofemoral Thrombosis: Early Surgical Thrombectomy Is Effective and
      Durable.
AB  - BACKGROUND: The first-line recommendation for the treatment of acute iliofemoral
      deep vein thrombosis (IFDVT) is catheter-directed thrombolysis or
      pharmacomechanical thrombolysis. Recent analysis of surgical thrombectomy has
      shown comparable results. However, this procedure is not commonly given as much
      importance as interventional techniques. We analyzed the patient outcome of
      surgical thrombectomy using modern endovascular techniques in both the short and
      long term. METHODS: All consecutive patients who underwent surgical thrombectomy
      at our institution between April 2008 and April 2017 were included. Only patients
      with iliofemoral thrombosis, and only those with the first onset of symptoms <10
      days, were analyzed. All patients received preoperative duplex ultrasound and
      contrast-enhanced computed tomography scans for thrombus extension and detection
      of pulmonary embolism. All operations were performed by vascular surgeons with
      open and endovascular skills in a C-arm-equipped operating room. During follow-up
      (FU), all patients received clinical examination for symptoms of postthrombotic
      syndrome (PTS), as well as duplex ultrasound. RESULTS: Within a 9-year period, 21
      patients underwent surgical thrombectomy for IFDVT (17 females/4 males). Primary
      technical success was 100%; 10 (47.6%) patients received additional primary
      stenting. 30-day mortality was 0%, 3 patients (14.3%) needed reoperation for
      early rethrombosis, while secondary 30-day patency was 100%. During FU (median, 6
      years; range, 1-104 months), 1 patient received additional stenting for stenosis
      of the common iliac vein. Nineteen patients (90.5%) presented patent iliofemoral
      veins without signs of rethrombosis. Two patients (9.5%) died during FU of cancer
      without signs for recurrent IFDVT. All patients with patent veins were free of
      symptoms for PTS. CONCLUSIONS: Surgical thrombectomy for acute IFDVT is a
      successful, safe, and durable procedure and provides alternative treatment
      options for acute IFDVT in selected cases.

PMID- 28739470
TI  - Iliac Stent Migration during Thoracic Endovascular Aortic Aneurysm Repair
      Resulting in Functional Coarctation.
AB  - Iliac arterial disease, unfavorable anatomy, and prior stenting all pose
      challenges to access in endovascular abdominal aortic repair (EVAR) and thoracic
      aortic repair (TEVAR). Iliac access injury during T/EVAR may lead to rupture,
      dissection, thrombosis, or distal ischemia. Some have advocated iliac stent prior
      to T/EVAR in patients with suboptimal iliac access. The rate of complication and
      iliac stent migration during subsequent T/EVAR is undocumented. This case report
      describes a unique instance of self-expanding iliac stent migration during TEVAR
      which pinched the thoracic aortic endograft causing functional aortic
      coarctation.

PMID- 28739471
TI  - Comparison of Low-Dose Catheter-Directed Thrombolysis with and without
      Pharmacomechanical Thrombectomy for Acute Lower Extremity Ischemia.
AB  - BACKGROUND: Catheter-directed thrombolysis (CDT) and/or pharmacomechanical
      thrombectomy (PMT) can dissolve/remove thrombus; PMT alone, however, may require
      the adjunctive use of CDT. The aim of this study was to compare the use of CDT
      with and without PMT for the treatment of acute lower extremity ischemia (ALI).
      METHODS: We retrospectively reviewed all patients with ALI who underwent CDT with
      or without PMT between January 2008 and April 2014 (n = 99). Patients with
      incomplete medical charts were excluded (n = 16). Remaining patients were divided
      into 2 cohorts: group 1 included patients who underwent PMT + CDT (n = 54); group
      2 included those who underwent CDT alone (n = 29). Lesions were further
      characterized by anatomic location: iliac disease (n = 14), femoropopliteal
      disease (n = 53), tibial disease (n = 2), and multilevel disease (n = 14). Data
      collection included patient and limb characteristics, duration of treatment,
      complications, clinical outcomes, adjunctive interventions, and follow-up.
      RESULTS: No significant differences were seen between treatment groups in terms
      of patient characteristics, occlusion length and location, Rutherford class,
      median duration of ischemia time (P = 0.22), or mean lysis time (P = 0.58).
      Treatment groups were also similar with regard to outcomes, including
      periprocedure complications, patency, reintervention, limb salvage, and
      amputation-free survival. CONCLUSIONS: There was no different between PMT + CDT
      and CDT alone in terms of periprocedural complications or outcomes. In the quest
      to resolve ALI, initial thrombus extraction with PMT may not reduce the need,
      duration, or efficacy of CDT.

PMID- 28739472
TI  - WITHDRAWN: Toll-like receptor-4 Signaling Improved the Migration of Sca
      1+stem/progenitor Cells.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 28739473
TI  - A Defined Protocol to Resolving Cannulation Failure during Endovenous Ablation
      Procedures.
AB  - During endovenous ablation for the treatment of insufficient veins, failure to
      cannulate the entirety of the refluxing vein with the treatment catheter prevents
      technically successful ablation. In this technique report, we describe a defined
      protocol to overcome cannulation failure of axial veins for endovenous ablation.
      This protocol utilizes commonly available adjunctive techniques including
      ultrasound-guided digital compression, the use of a guidewire, the use of a guide
      catheter, and placement of a second puncture site in a step-wise fashion to
      overcome varying degrees of tortuosity or obstruction. The sequential application
      of these techniques as described in this report allows endovenous ablation to be
      applied to patients with challenging venous anatomy.

PMID- 28739474
TI  - Traumatic subaxial cervical facet subluxation and dislocation: epidemiology,
      radiographic analyses, and risk factors for spinal cord injury.
AB  - BACKGROUND CONTEXT: Distractive flexion injuries (DFIs) of the subaxial cervical
      spine are major contributors to spinal cord injury (SCI). Prompt assessment and
      early intervention of DFIs associated with SCI are crucial to optimize patient
      outcome; however, neurologic examination of patients with subaxial cervical
      injury is often difficult, as patients commonly present with reduced levels of
      consciousness. Therefore, it is important to establish potential associations
      between injury epidemiology and radiographic features, and neurologic
      involvement. PURPOSE: The aims of this study were to describe the epidemiology
      and radiographic features of DFIs presenting to a major Australian tertiary
      hospital and to identify those factors predictive of SCI. The agreement and
      repeatability of radiographic measures of DFI severity were also investigated.
      STUDY DESIGN/SETTING: This is a combined retrospective case-control and
      reliability-agreement study. PATIENT SAMPLE: Two hundred twenty-six patients
      (median age 40 years [interquartile range = 34]; 72.1% male) who presented with a
      DFI of the subaxial cervical spine between 2003 and 2013 were reviewed. OUTCOME
      MEASURES: The epidemiology and radiographic features of DFI, and risk factors for
      SCI were identified. Inter- and intraobserver agreement of radiographic
      measurements was evaluated. METHODS: Medical records, radiographs, and computed
      tomography and magnetic resonance imaging scans were examined, and the presence
      of SCI was evaluated. Radiographic images were analyzed by two consultant spinal
      surgeons, and the degree of vertebral translation, facet apposition, spinal canal
      occlusion, and spinal cord compression were documented. Multivariable logistic
      regression models identified epidemiology and radiographic features predictive of
      SCI. Intraclass correlation coefficients (ICCs) examined inter- and intraobserver
      agreement of radiographic measurements. RESULTS: The majority of patients (56.2%)
      sustained a unilateral (51.2%) or a bilateral facet (48.8%) dislocation. The C6
      C7 vertebral level was most commonly involved (38.5%). Younger adults were over
      represented among motor-vehicle accidents, whereas falls contributed to a
      majority of DFIs sustained by older adults. Greater vertebral translation,
      together with lower facet apposition, distinguished facet dislocation from
      subluxation. Dislocation, bilateral facet injury, reduced Glasgow Coma Scale,
      spinal canal occlusion, and spinal cord compression were predictive of neurologic
      deficit. Radiographic measurements demonstrated at least a "moderate" agreement
      (ICC>0.4), with most demonstrating an "almost perfect" reproducibility.
      CONCLUSIONS: This large-scale cohort investigation of DFIs in the cervical spine
      describes radiographic features that distinguish facet dislocation from
      subluxation, and associates highly reproducible anatomical and clinical indices
      to the occurrence of concomitant SCI.

PMID- 28739475
TI  - Posterior osteosynthesis with monoaxial lateral mass screw-rod system for
      unstable C1 burst fractures.
AB  - BACKGROUND CONTEXT: Surgical treatment for unstable atlas fractures has evolved
      in recent decades from C1-C2 or C0-C2 fusion to motion-preservation techniques of
      open reduction and internal fixation (ORIF). However, regardless of a transoral
      or a posterior approach, the reduction is still not satisfactory. PURPOSE: The
      article describes and evaluates a new technique for treating unstable atlas
      fractures by using a monoaxial screw-rod system. STUDY DESIGN: This is a
      retrospective study. PATIENT SAMPLE: The sample includes adult patients with
      unstable C1 fractures treated with a posterior monoaxial screw-rod system.
      OUTCOME MEASURES: The outcome measures included a visual analog pain scale,
      radiographic reduction (lateral mass displacement [LMD]), maintenance of
      reduction, C1-C2 instability (anterior atlantodens interval), and complications.
      MATERIALS AND METHODS: From August 2013 to May 2016, nine consecutive patients
      with unstable atlas fractures were retrospectively reviewed. All patients were
      treated with posterior ORIF by using a monoaxial screw-rod system. The medical
      records and the preoperative and postoperative radiographs were reviewed.
      Preoperative and postoperative computed tomography scans were used to specify the
      fracture types and to assess the reduction. RESULTS: All nine patients with a
      mean age of 50.3 years successfully underwent surgery with this technique, and a
      follow-up of 17.4+/-9.3 months was performed. Transverse atlantal ligament (TAL)
      injury was found in eight of the nine patients: one of type I and seven of type
      II. The preoperative LMD averaged 7.0+/-2.2 mm and was restored completely after
      surgery; all the fractures achieved bony healing without loss of reduction or
      implant failure. None of the patients had complications of neurologic deficit,
      vertebral artery injury, or wound infection associated with the surgical
      procedure. Two patients complained of greater occipital nerve neuralgia after the
      operation, which gradually disappeared in 1 month. All patients had a well
      preserved range of motion of the upper cervical spine at the final follow-up.
      CONCLUSIONS: Posterior osteosynthesis with a monoaxial screw-rod system is
      capable of an almost anatomical reduction for the unstable atlas fractures. The
      TAL incompetence may not be a contraindication to ORIF for C1 fractures, but the
      long-term effect of C1-C2 instability remains to be further investigated.

PMID- 28739476
TI  - Severity of foraminal lumbar stenosis and the relation to clinical symptoms and
      response to periradicular infiltration-introduction of the "melting sign".
AB  - BACKGROUND CONTEXT: Nerve root compression causing symptomatic radiculopathy can
      occur within the intervertebral foramen. Sagittal magnetic resonance imaging
      (MRI) sequences are reliable in detection of nerve root contact to intraforaminal
      disc material, but a clinically relevant classification of degree of contact is
      lacking. PURPOSE: This study aimed to investigate a potential relation of amount
      of contact between intraforaminal disc material and nerve root to clinical
      findings and response after periradicular corticosteroid infiltration. STUDY
      DESIGN: A post hoc analysis of a prospective cohort was carried out. PATIENT
      SAMPLE: Patients who underwent computed tomography (CT)-guided periradicular
      corticosteroid infiltration (L1-L5) at our institution (January 2014 to May 2016)
      were included. OUTCOME MEASURES: The medical records and radiographic imaging
      were reviewed. METHODS: T2-weighted MRI of the lumbar spine of patients with
      single-level symptomatic radiculopathy with (responders, n=28) or without (non
      responders, n=14) pain relief after periradicular infiltration with
      corticosteroids were measured and compared by two independent readers to
      determine the amount of intraforaminal nerve root contact with the intervertebral
      disc ("melting" of the T2-hypointense signal). Pain relief was defined with a
      pain level decrease of >50% on a visual analogue scale and lack of pain relief
      with a pain level decrease of <25%, respectively. The amount of T2-hypointensity
      melting of disc and nerve root was categorized to 0%, 1%-25%, and over 25%.
      RESULTS: Reader one identified 0% T2-melting in none of the responders, 1%-25%
      melting in 13 patients (46.4%), 26%-50% in 15 of the 28 patients (53.6%) with
      pain relief after periradicular corticosteroid infiltration (responders), with a
      mean amount of T2-melting of 5.9+/-2.1 mm, whereas the non-responder group had 0%
      T2-melting in 2 patients (14.3%), 1%-25% T2-melting in 11 patients (78.6%), and
      26%-50% in 1 patient (7.1%), with a mean amount of T2-melting of 2.6+/-1.9 mm
      (p<.05). Reader two identified 0% T2-melting in none, 1%-25% T2-melting in 15
      (53.6%) patients, and 26%-50% in 13 of the 28 responders (46.4%), with mean
      amount of 6.3+/-1.9 mm. In the non-responder group 0% T2-melting was seen in 3
      patients (21.4%), 1%-25% T2-melting in 10 patients (71.4%), and 26%-50% in 1
      patient (7.1%), with a mean amount of T2-melting of 2.7+/-1.9 mm (p<.05). None of
      the MRI showed T2-melting in over 50% of the circumference of the intraforaminal
      nerve root. A T2-melting of >25% had a high specificity of 93% but a sensitivity
      of 50%, thus a positive likelihood ratio of 7.5, to identify those with a pain
      relief of more than 50% after infiltration. CONCLUSION: The amount of T2-melting
      of disc material and nerve root on sagittal MRI (>25%) predicts the amount of
      pain relief by periradicular infiltration in patients with intraforaminal nerve
      root irritation.

PMID- 28739477
TI  - Predictors of increased cost and length of stay in the treatment of postoperative
      spine surgical site infection.
AB  - BACKGROUND CONTEXT: Although many risk factors are known to contribute to the
      development of a postoperative surgical site infection (SSI) following spinal
      surgery, little is known regarding the costs associated with the management of
      this complication, or the predictors for which patients will require increased
      resources for the management of SSI. PURPOSE: The aim of this study was to
      identify specific risk factors for increased treatment costs and length of stay
      in the management of a postoperative SSI. STUDY DESIGN/SETTING: This is a
      retrospective cohort study of all patients undergoing spine surgery at a single
      institution for 3 consecutive years. PATIENT SAMPLE: The study included 90
      patients who were required to return to the operating room following spine
      surgery for postoperative SSI. OUTCOME MEASURES: The primary outcome measure was
      length of stay and hospital costs for patients with postoperative SSI following
      spine surgery at a single institution. METHODS: A retrospective review of all
      patients undergoing spine surgery at a single institution for 3 consecutive years
      was performed to identify patients requiring secondary surgical intervention for
      SSI. Demographic and financial data from both the index admission and all
      subsequent readmissions within 2 years of the index procedure were reviewed.
      Independent variables abstracted from patient records were analyzed to determine
      the nature and the extent of their associations with total direct hospital costs
      and length of stay. RESULTS: A total of 90 patients were identified that resulted
      in 110 readmissions, and these patients cumulatively underwent 138 irrigation and
      debridement (I&D) procedures for the management of postoperative spine SSI. The
      average length of stay for the index operation and secondary readmissions were
      6.9 and 9.6 days, respectively. The mean direct cost of the treatment for SSI was
      $16,242. The length of stay, the number of levels fused, methicillin-resistant
      Staphylococcus aureus (MRSA), decreased serum albumin on readmission, and the
      number of I&D procedures required were significantly associated with increased
      treatment costs. CONCLUSIONS: Preoperative nutritional status assessment and MRSA
      colonization screening with targeted prophylaxis represent potentially modifiable
      risk factors in the treatment of SSI. Further study is needed to investigate the
      relationship between poor nutrition status and increased length of stay and total
      costs in the treatment of SSI following spine surgery.

PMID- 28739478
TI  - An overview of clinical guidelines for the management of vertebral compression
      fracture: a systematic review.
AB  - BACKGROUND CONTEXT: Vertebral compression fractures (VCFs) are the most common
      type of osteoporotic fracture comprising approximately 1.4 million cases
      worldwide. Clinical practice guidelines can be powerful tools for promoting
      evidence-based practice as they integrate research findings to support decision
      making. However, currently available clinical guidelines and recommendations,
      established by different medical societies, are sometimes contradictory. PURPOSE:
      The aim of this study was to appraise the recommendations and the methodological
      quality of international clinical guidelines for the management of VCFs. STUDY
      DESIGN: This is a systematic review of clinical guidelines for the management of
      VCF. METHODS: Guidelines were selected by searching MEDLINE and PubMed, PEDro,
      CINAHL, and EMBASE electronic databases between 2010 and 2016. We also searched
      clinical practice guideline databases, including the National Guideline
      Clearinghouse and the Canadian Medical Association InfoBase. The methodological
      quality of the guidelines was assessed by two authors independently using the
      Appraisal of Guidelines, Research and Evaluation (AGREE) II Instrument. We also
      classified the strength of each recommendation as either strong (ie, based on
      high-quality studies with consistent findings for recommending for or against the
      intervention), weak (ie, based on a lack of compelling evidence resulting in
      uncertainty for benefit or potential harm), or expert consensus (ie, based on
      expert opinion of the working group rather than on scientific evidence).
      Guideline recommendations were grouped into diagnostic, conservative care,
      interventional care, and osteoporosis treatment and prevention of future
      fractures. Our study was prospectively registered on PROSPERO. RESULTS: Four
      guidelines from three countries, published in the period 2010-2013, were
      included. In general, the quality was not satisfactory (50% or less of the
      maximum possible score). The domains scoring 50% or less of the maximum possible
      score were rigor of development, clarity of presentation, and applicability. The
      use of plain radiography or dual-energy X-ray absorptiometry for diagnosis was
      recommended in two of the four guidelines. Vertebroplasty or kyphoplasty was
      recommended in three of the four guidelines. The recommendation for bed rest,
      trunk orthoses, electrical stimulation, and supervised or unsupervised exercise
      was inconsistent across the included guidelines. CONCLUSIONS: The comparison of
      clinical guidelines for the management of VCF showed that diagnostic and
      therapeutic recommendations were generally inconsistent. The evidence available
      to guideline developers was limited in quantity and quality. Greater efforts are
      needed to improve the quality of the majority of guidelines.

PMID- 28739479
TI  - Emergency department visits after lumbar spine surgery are associated with lower
      Hospital Consumer Assessment of Healthcare Providers and Systems scores.
AB  - BACKGROUND: Hospital Consumer Assessment of Healthcare Providers and Systems
      (HCAHPS) surveys are used to assess the quality of the patient experience
      following an inpatient stay. Hospital Consumer Assessment of Healthcare Providers
      and Systems scores are used to determine reimbursement for hospital systems and
      incentivize spine surgeons nationwide. There are conflicting data detailing
      whether early readmission or other postdischarge complications are associated
      with patient responses on the HCAHPS survey. Currently, the association between
      postdischarge emergency department (ED) visits and HCAHPS scores following lumbar
      spine surgery is unknown. PURPOSE: To determine whether ED visits within 30 days
      of discharge are associated with HCAHPS scores for patients who underwent lumbar
      spine surgery. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: A total
      of 453 patients who underwent lumbar spine surgery who completed the HCAHPS
      survey between 2013 and 2015 at a single tertiary care center. OUTCOME MEASURES:
      The HCAHPS survey-the Centers for Medicare and Medicaid Services' official
      measure of patient experience-results for each patient were analyzed as the
      primary outcome of this study. METHODS: All patients undergoing lumbar spine
      surgery between 2013 and 2015 who completed an HCAHPS survey were studied.
      Patients were excluded from the study if they had been diagnosed with spinal
      malignancy or scoliosis. Patients who had an ED visit at our institution within
      30 days of discharge were included in the ED visit cohort. The primary outcomes
      of this study include 21 measures of patient experience on the HCAHPS survey.
      Statistical analysis included Pearson chi-square for categorical variables,
      Student t test for normally distributed continuous variables, and Mann-Whitney U
      test for nonparametric variables. Additionally, log-binomial regression models
      were used to analyze the association between ED visits within 30 days after
      discharge and odds of top-box HCAHPS scores. No funds were received in support of
      this study, and the authors report no conflict of interest-associated biases.
      RESULTS: After adjusting for patient-level covariates using log-binomial
      regression models, we found postdischarge ED visits were independently associated
      with lower likelihood of top-box score for several individual questions on
      HCAHPS. Emergency department visits within 30 days of discharge were negatively
      associated with perceiving your doctor as "always" treating you with courtesy and
      respect (risk ratio [RR] 0.26, p<.001), as well as perceiving your doctor as
      "always" listeningcarefully to you (RR 0.40, p=.003). Also, patients with an ED
      visit were less likely to feel as if their preferences were taken into account
      when leaving the hospital (RR 0.61, p=.008), less likely to recommend the
      hospital to family or friends (RR 0.46, p=.020), and less likely to rate the
      hospital as a 9 or a 10 out of 10, the top-box score (RR 0.43, p=.005).
      CONCLUSIONS: Our results demonstrate a strong association between postdischarge
      ED visits and low HCAHPS scores for doctor communication, discharge information,
      and global measures of hospital satisfaction in a lumbar spine surgery
      population.

PMID- 28739480
TI  - The Changing Face of Aging: Highly Sulfated Glycosaminoglycans Induce Amyloid
      Formation in a Lattice Corneal Dystrophy Model Protein.
AB  - Glycosaminoglycans (GAGs) are related to multiple biological functions and
      diseases. There is growing evidence that GAG concentration and sulfate content
      increase with age. The destabilizing mutation A546T in the corneal protein TGFBIp
      leads to lattice-type corneal dystrophy, but symptoms only appear in the fourth
      decade of life. We hypothesize that this delayed phenotype can be explained by
      increased GAG sulfation over time. Using in vitro assays with the C-terminal
      TGFIBIp domain Fas1-4, previously shown to recapitulate many properties of full
      length TGFBIp, we find that only long GAGs with multiple sulfate groups on each
      repeating unit increase the amount of worm-like aggregates and induce long,
      straight fibrils in A546T. In contrast, GAGs did not induce aggregation of
      wildtype Fas1-4, suggesting that the finding might be specific for lattice
      corneal dystrophy mutants. Our results highlight a possible role of changing GAG
      sulfation in the accumulation of amyloid, which also may have implications for
      the development of neurodegenerative diseases.

PMID- 28739481
TI  - Group and individual analyses of pre-, peri-, and post-movement related alpha and
      beta oscillations during a single continuous monitoring task.
AB  - Band power linked to lower and upper alpha (i.e. 8-10Hz; 10-12Hz) and lower and
      upper beta (i.e. 12-20Hz; 20-30Hz) were examined during response related stages,
      including anticipation, response execution (RE), response inhibition (RI) and
      post response recovery (PRR). Group and individual data from 34 participants were
      considered. The participant's objective was to press a response key immediately
      following 4 non-repeating, single integer odd digits. These were presented
      amongst a continuous stream of digits and Xs. Electroencephalogram (EEG) signals
      were recorded from 32 electrodes (pooled to 12 regions). In the group analyses,
      participant EEG response was compared to baseline revealing that upper alpha
      desynchronised during anticipation, RE and RI; lower beta during anticipation and
      RE; and upper beta just RE. Upper alpha desynchronisation during rapid, unplanned
      RI is novel. Also, upper alpha and lower/upper beta synchronised during PRR. For
      upper alpha, we speculate this indexes brief cortical deactivation; for beta we
      propose this indexes response set maintenance. Lastly, lower alpha fluctuations
      correlated negatively with RT, indexing neural efficiency. Individual analyses
      involved calculation of the proportion of individuals displaying the typical RE
      and PRR trends; these were not reflected by all participants. The former was
      displayed individually by the largest proportion in upper alpha recorded left
      fronto-centrally; the latter was most reliably displayed individually in lower
      beta recorded mid centro-parietally. Therefore, group analyses identified typical
      alpha and beta synchronisation/desynchronisation trends, whilst individual
      analyses identified their degree of representation in single participants.
      Attention is drawn to the clinical relevance of this issue.

PMID- 28739482
TI  - Brain responses to 40-Hz binaural beat and effects on emotion and memory.
AB  - Gamma oscillation plays a role in binding process or sensory integration, a
      process by which several brain areas beside primary cortex are activated for
      higher perception of the received stimulus. Beta oscillation is also involved in
      interpreting received stimulus and occurs following gamma oscillation, and this
      process is known as gamma-to-beta transition, a process for neglecting
      unnecessary stimuli in surrounding environment. Gamma oscillation also associates
      with cognitive functions, memory and emotion. Therefore, modulation of the brain
      activity can lead to manipulation of cognitive functions. The stimulus used in
      this study was 40-Hz binaural beat because binaural beat induces frequency
      following response. This study aimed to investigate the neural oscillation
      responding to the 40-Hz binaural beat and to evaluate working memory function and
      emotional states after listening to that stimulus. Two experiments were developed
      based on the study aims. In the first experiment, electroencephalograms were
      recorded while participants listened to the stimulus for 30min. The results
      suggested that frontal, temporal, and central regions were activated within
      15min. In the second experiment, word list recall task was conducted before and
      after listening to the stimulus for 20min. The results showed that, after
      listening, the recalled words were increase in the working memory portion of the
      list. Brunel Mood Scale, a questionnaire to evaluate emotional states, revealed
      changes in emotional states after listening to the stimulus. The emotional
      results suggested that these changes were consistent with the induced neural
      oscillations.

PMID- 28739483
TI  - Structural modeling for the open state of an NMDA receptor.
AB  - NMDA receptors are tetrameric ligand-gated ion channels that are crucial for
      neurodevelopment and higher order processes such as learning and memory, and have
      been implicated in numerous neurological disorders. The lack of a structure for
      the channel open state has greatly hampered the understanding of the normal
      gating process and mechanisms of disease-associated mutations. Here we report the
      structural modeling for the open state of an NMDA receptor. Staring from the
      crystal structure of the closed state, we repacked the pore-lining helices to
      generate an initial open model. This model was modified to ensure tight packing
      between subunits and then refined by a molecular dynamics simulation in explicit
      membrane. We identify Calpha-H...O hydrogen bonds, between the Calpha of a
      conserved glycine in one transmembrane helix and a carbonyl oxygen of a membrane
      parallel helix, at the extracellular side of the transmembrane domain as
      important for stabilizing the open state. This observation explains why mutations
      of the glycine are associated with neurological diseases and lead to significant
      decrease in channel open probability.

PMID- 28739484
TI  - Protein kinase Ciota/lambda is dispensable for platelet function in thrombosis
      and hemostasis in mice.
AB  - Platelet activation at sites of vascular injury is crucial for hemostasis, but it
      may also cause myocardial infarction or ischemic stroke. Upon platelet
      activation, cytoskeletal reorganization is essential for platelet secretion and
      thrombus formation. Members of the protein kinase C family, which includes 12
      isoforms, are involved in most platelet responses required for thrombus
      formation. The atypical protein kinase Ciota/lambda (PKCiota/lambda) has been
      implicated as an important mediator of cell polarity, carcinogenesis and immune
      cell responses. PKCiota/lambda is known to be associated with the small GTPase
      Cdc42, an important mediator of multiple platelet functions; however, its exact
      function in platelets is not known. To study the role of PKCiota/lambda, we
      generated platelet- and megakaryocyte-specific PKCiota/lambda knockout mice
      (Prkcifl/fl, Pf4-Cre) and used them to investigate the function of PKCiota/lambda
      in platelet activation and aggregation in vitro and in vivo. Surprisingly, lack
      of PKCiota/lambda had no detectable effect on platelet spreading and function in
      vitro and in vivo under all tested conditions. These results indicate that
      PKCiota/lambda is dispensable for Cdc42-triggered processes and for thrombosis
      and hemostasis in mice.

PMID- 28739485
TI  - HSP90 is necessary for the ACK1-dependent phosphorylation of STAT1 and STAT3.
AB  - Signal transducers and activators of transcription (STATs) are latent,
      cytoplasmic transcription factors. Janus kinases (JAKs) and activated CDC42
      associated kinase-1 (ACK1/TNK2) catalyse the phosphorylation of STAT1 and the
      expression of its target genes. Here we demonstrate that catalytically active
      ACK1 promotes the phosphorylation and nuclear accumulation of STAT1 in
      transformed kidney cells. These processes are associated with STAT1-dependent
      gene expression and an interaction between endogenous STAT1 and ACK1. Moreover,
      the E3 ubiquitin ligase seven-in-absentia homolog-2 (SIAH2), which targets ACK1
      through valine-909 for proteasomal degradation, attenuates the ACK1-STAT1
      signalling node. We further show that ACK1 promotes the phosphorylation and
      nuclear accumulation of STAT3 in cultured cells and that the levels of ACK1
      correlate positively with the levels of tyrosine phosphorylated STAT3 in primary
      lung adenocarcinoma (ADC) cells. Global analysis of ACK1 interaction partners
      validated the interaction of ACK1 with heat shock protein 90 (HSP90alpha/beta).
      Inhibition of this chaperone with the novel drug Onalespib (AT13387) demonstrates
      that HSP90 is an upstream regulator of the ACK1-dependent phosphorylation of
      STAT1 and STAT3. In addition to these molecular insights, our data offer a
      pharmacological strategy to control the ACK1-STAT signalling axis.

PMID- 28739486
TI  - MicroRNA-146a-5p attenuates liver fibrosis by suppressing profibrogenic effects
      of TGFbeta1 and lipopolysaccharide.
AB  - Liver fibrosis is characterized by proliferation and activation of hepatic
      stellate cells (HSCs). Transforming growth factor-beta1 (TGFbeta1) is crucial for
      liver fibrogenesis, and gut-derived endotoxin (LPS) also plays an important role
      in liver fibrogenesis. In the present study, we found that microRNA-146a-5p (miR
      146a-5p) could regulate TGFbeta1/Smad and LPS/NF-kappaB/Bambi pathways to
      attenuate liver fibrosis. Downregulated miR-146a-5p and upregulated level of LPS
      were found in liver of CCl4-treated rats. On cellular level, expression of miR
      146a-5p is reduced during primary rat HSCs naturally activation and changed in
      response to TGFbeta1 and/or LPS stimulation in primary rat HSCs and human HSC
      line LX-2. Further overexpression of miR-146a-5p suppresses proliferation and
      activation of HSCs. The underlying mechanism involved that miR-146a-5p directly
      suppresses profibrogenic effects of TGFbeta1 by down-regulating the expression of
      Smad4 and phosphorylation of Smad2. Moreover, miR-146a-5p indirectly suppresses
      TGFbeta1/Smad pathway by targeting IL-1 receptor-associated kinase 1 (IRAK1) and
      TNF receptor associated factor-6 (TRAF6), two major components of LPS/NF
      kappaB/Bambi pathway, to reduce inhibition of TGFbeta pseudoreceptor Bambi. These
      results indicate that miR-146a-5p abrogate hepatic fibrosis by suppressing both
      TGFbeta/Smad and LPS/NF-kappaB/Bambi signaling pathway in HSCs and suggest that
      miR-146a-5p is a potential therapeutic target for liver fibrosis.

PMID- 28739487
TI  - The ROS-mediated activation of IL-6/STAT3 signaling pathway is involved in the 27
      hydroxycholesterol-induced cellular senescence in nerve cells.
AB  - The oxysterol 27-hydroxycholesterol (27HC) is a selective estrogen receptor
      modulator (SERMs), which like endogenous estrogen 17beta-estradiol (E2) induces
      the proliferation of ER-positive breast cancer cells in vitro. Interestingly, the
      observation that 27HC induces adverse effects in neural system, distinguishing it
      from E2. It has been suggested that high levels of circulating cholesterol
      increase the entry of 27HC into the brain, which may induce learning and memory
      impairment. Based on this evidence, 27HC may be associated with neurodegenerative
      processes and interrupted cholesterol homeostasis in the brain. However, the
      biological events that participate in this process remain largely elusive. In the
      present study, we demonstrated that 27HC induced apparent cellular senescence in
      nerve cells. Senescence-associated beta-galactosidase (SA-beta-Gal) assay
      revealed that 27HC induced senescence in both BV2 cells and PC12 cells.
      Furthermore, we demonstrated that 27HC promoted the accumulation of cellular
      reactive oxygen species (ROS) in nerve cells and subsequently activation of IL
      6/STAT3 signaling pathway. Notably, treatment with the ROS scavenger N
      acetylcysteine (NAC) markedly blocked 27HC-induced ROS production and activation
      of IL-6/STAT3 signaling pathway. Either blocking the generation of ROS or
      inhibition of IL-6/STAT3 both attenuated 27HC-induced cellular senescence. In
      sum, these findings not only suggested a mechanism whereby 27HC induced cellular
      senescence in nerve cells, but also helped to recognize the 27HC as a novel
      harmful factor in neurodegenerative diseases.

PMID- 28739488
TI  - Nanosilver-PMMA composite coating optimized to provide robust antibacterial
      efficacy while minimizing human bone marrow stromal cell toxicity.
AB  - Porous PMMA is a versatile biomaterial with good biocompatibility but high
      susceptibility to bacterial colonization, which we mitigated by utilizing
      immobilized antimicrobial silver nanoparticles (AgNPs). A uniform porous thin
      film was deposited onto silicon wafers by simultaneously ablating PMMA and silver
      (Ag) using pulsed laser deposition (PLD) optimized for minimal human cell
      toxicity and antibacterial efficacy. PMMA without Ag became heavily colonized by
      E. coli in simulated dynamic conditions, while Ag-containing samples prevented
      all colonization. ICP-MS analysis demonstrated that the amount of leached Ag
      after 24h under simulated in vivo conditions (with serum media at 37 degrees C
      and 5% CO2) increased in proportion to film thickness (and total silver content).
      10,000, 14,000, and 20,000 laser pulse-deposited films released 0.76, 1.05, and
      1.67MUg/mL Ag, respectively, after 24h. Human bone marrow stromal cells (hBMSCs)
      grown directly on 10,000-pulse films (0.76MUg/mL Ag released) for 24-h exhibited
      no cytotoxicity. Exposure to the remaining films produced cytotoxicity, necrosis,
      and apoptosis detected using flow cytometry. Examining both leachates and direct
      cell contact allowed us to develop an in vitro cytotoxicity test method and
      optimize a novel device material and coating to be nontoxic and bactericidal
      during both potential initial implantation and external use.

PMID- 28739489
TI  - Colonoscopy and sigmoidoscopy use among older adults in different countries: A
      systematic review.
AB  - Screening for colorectal cancer (CRC) by colonoscopy and sigmoidoscopy has been
      demonstrated to be effective in reducing CRC incidence and mortality, and they
      are increasingly employed as screening tests and for diagnostic purposes in many
      countries. We conducted a systematic review to provide up-to-date estimates on
      the utilization of lower gastrointestinal endoscopy (colonoscopy and
      sigmoidoscopy) in the general average-risk population in different countries.
      PubMed and Web of Science were searched for relevant articles published between 1
      September 2008 and 31 October 2016. A total of 23 studies from the US and 20
      studies from other countries were included in this review. Estimates from the US
      were highest, continued to increase over the past decade and reached 62% for
      colonoscopy use within 10years in people aged 50-75years in 2012. Endoscopy use
      in other countries was substantially lower (12-44% for lifetime colonoscopy use
      and 13-30% for recent colonoscopy use), except for Germany, where 55% of the
      screening-eligible population reported colonoscopy utilization within the
      previous 10years in 2008-2011. Both lifetime and recent endoscopy use increased
      with age and peaked at approximately 70-75years. Although several European and
      Asian countries have started to collect endoscopy utilization data through
      periodic national health surveys, more data are still much needed from non-US
      countries. With the implementation of CRC screening programs in an increasing
      number of countries, especially European countries, an increase in endoscopy use
      and subsequent reduction in CRC incidence and mortality in the years to come
      might be expected in those countries.

PMID- 28739490
TI  - Are single children more likely to be overweight or obese than those with
      siblings? The influence of China's one-child policy on childhood obesity.
AB  - China's one-child policy (1979-2015) has affected Chinese parenting practices and
      children's health behaviors and also may have contributed to increased childhood
      obesity. However, very limited research has investigated the association between
      one-child policy and childhood obesity. We examined characteristics of single
      child families and the influence of one-child policy (indicated by single-child
      status) on children's weight status and related health behaviors. Data from
      children aged 6-18years old in the 2011 (n=1580) and 2000 (n=2317) China Health
      and Nutrition Survey were cross-sectionally analyzed with multilevel models. From
      2000 to 2011, the rates about doubled for being a single-child (30.1% to 57.0%)
      and being overweight or obese (OWB, 6.6% to 16.5%) along with urbanization (27.5%
      to 37.1%). Single-child families had higher levels of parental education,
      household income and urban residence than families with >= two children (p<0.05).
      Compared to the children with siblings, single children were more likely to be
      OWB; the association became stronger over time (OR=4.5 (1.7-12.4) in 2011 and 1.7
      (1.0-2.8) in 2000). Also, single children had less recreational screen time, but
      similar physical activity levels; however single urban children were more likely
      to have excess total energy intake (OR=5.70 (1.58-20.60)) than those with
      siblings. Being single-child is about four times more likely to be
      overweight/obesity than those having siblings, and the association became
      stronger over time in China. China's one-child policy might have contributed to
      its rising childhood obesity rates. Obesity intervention programs may need to
      account for the influence of the one-child policy in China.

PMID- 28739491
TI  - Management of Fecal Incontinence in Older People With Dementia Resident in Care
      Homes: A Realist Synthesis-The FINCH Study.

PMID- 28739492
TI  - Efficacy and Safety of Citalopram Compared to Atypical Antipsychotics on
      Agitation in Nursing Home Residents With Alzheimer Dementia.
AB  - OBJECTIVE: To assess efficacy and safety of citalopram compared to quetiapine and
      olanzapine for the treatment of agitation in patients with Alzheimer disease
      (AD). DESIGN: Longitudinal, 6-month study. SETTING: Nursing home (NH).
      PARTICIPANTS: 75 NH residents with AD and agitation, randomized to citalopram (n
      = 25), quetiapine (n = 25), or olanzapine (n = 25). MEASUREMENTS: Changes in
      Neuropsychiatric Inventory (NPI) agitation subscale score and the modified
      Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS
      CGIC) were used to assess treatment efficacy. Participants were surveilled for
      adverse health outcomes. RESULTS: Citalopram treatment (30+/-5.8 mg/d) resulted
      in similar 6-month efficacy compared to both quetiapine (94.0+/-40.4 mg/d) and
      olanzapine (5.2+/-1.6 mg/d), lower occurrence of falls than olanzapine [odds
      ratio (OR) = 0.81, 95% confidence interval (CI) = 0.68-0.97, P = .012], lower
      incidence of orthostatic hypotension than both quetiapine (OR = 0.80, 95% CI =
      0.66-0.95, P = .032) and olanzapine (OR = 0.75, 95% CI = 0.69-0.91, P = .02), and
      less all-cause hospitalizations than both quetiapine (OR = 0.92, 95% CI = 0.88
      0.95, P = .016) and olanzapine (OR = 0.78, 95% CI = 0.64-0.92, P = .004), after
      multiple adjustment for potentially confounding variables. No differences were
      observed for cognitive and functional decline, QTc prolongation, and infections.
      CONCLUSIONS: Citalopram resulted in similar efficacy and less adverse outcomes
      when compared to 2 atypical antipsychotics for treatment of agitation in NH
      residents with AD. Replication of these findings and assessment of long-term
      efficacy and safety of citalopram for treatment of neuropsychiatric symptoms in
      dementia are needed.

PMID- 28739493
TI  - Association Between Sarcopenia and Mild Cognitive Impairment Using the Japanese
      Version of the SARC-F in Elderly Patients With Diabetes.
AB  - OBJECTIVES: The purpose of this study was to investigate the association between
      sarcopenia and mild cognitive impairment (MCI) in elderly patients with diabetes
      using the Japanese version of the simple 5-item questionnaire (SARC-F-J). DESIGN:
      Cross-sectional study. SETTING: Community hospital in Japan. PARTICIPANTS:
      Subjects were people with diabetes aged 65 years and older being treated on an
      outpatient basis at the Ise Red Cross Hospital. MEASUREMENTS: We used the
      Japanese version of the self-administered cognitive test Test Your Memory (TYM-J)
      to measure MCI and the self-administered questionnaire SARC-F-J, consisting of 5
      items, to evaluate sarcopenia. We conducted a multiple logistic regression
      analysis with MCI as the dependent variable and sarcopenia as the explanatory
      variable to calculate the odds ratio of sarcopenia in association with MCI.
      RESULTS: A total of 250 cases (150 men and 100 women) were included in our study.
      The prevalence of sarcopenia in this sample was 19.5% and that of MCI was 40.3%.
      The adjusted odds ratio of sarcopenia in association with MCI was 2.96 (95%
      confidence interval, 1.09-7.70, P = .032). CONCLUSION: A statistically
      significant association was found between sarcopenia and MCI in an assessment of
      elderly patients with diabetes using the SARC-F-J.

PMID- 28739494
TI  - Amblyomma maculatum SECIS binding protein 2 and putative selenoprotein P are
      indispensable for pathogen replication and tick fecundity.
AB  - Selenium, a vital trace element, is incorporated into selenoproteins to produce
      selenocysteine. Our previous studies have revealed an adaptive co-evolutionary
      process that has enabled the spotted fever-causing tick-borne pathogen Rickettsia
      parkeri to survive by manipulating an antioxidant defense system associated with
      selenium, which includes a full set of selenoproteins and other antioxidants in
      ticks. Here, we conducted a systemic investigation of SECIS binding protein 2
      (SBP2) and putative selenoprotein P (SELENOP) by transcript silencing in adult
      female Gulf-coast ticks (Amblyomma maculatum). Knockdown of the SBP2 and SELENOP
      genes depleted the respective transcript levels of these tick selenogenes, and
      caused differential regulation of other antioxidants. Importantly, the selenium
      level in the immature and mature tick stages increased significantly after a
      blood meal, but the selenium level decreased in ticks after the SBP2 and SELENOP
      knockdowns. Moreover, the SBP2 knockdown significantly impaired both transovarial
      transmission of R. parkeri to tick eggs and egg hatching. Overall, our data offer
      new insight into the relationship between the SBP2 selenoprotein synthesis gene
      and the putative tick SELENOP gene. It also augments our understanding of
      selenoprotein synthesis, selenium maintenance and utilization, and bacterial
      colonization of a tick vector.

PMID- 28739495
TI  - The Deep Thioredoxome in Chlamydomonas reinhardtii: New Insights into Redox
      Regulation.
AB  - Thiol-based redox post-translational modifications have emerged as important
      mechanisms of signaling and regulation in all organisms, and thioredoxin plays a
      key role by controlling the thiol-disulfide status of target proteins. Recent
      redox proteomic studies revealed hundreds of proteins regulated by
      glutathionylation and nitrosylation in the unicellular green alga Chlamydomonas
      reinhardtii, while much less is known about the thioredoxin interactome in this
      organism. By combining qualitative and quantitative proteomic analyses, we have
      comprehensively investigated the Chlamydomonas thioredoxome and 1188 targets have
      been identified. They participate in a wide range of metabolic pathways and
      cellular processes. This study broadens not only the redox regulation to new
      enzymes involved in well-known thioredoxin-regulated metabolic pathways but also
      sheds light on cellular processes for which data supporting redox regulation are
      scarce (aromatic amino acid biosynthesis, nuclear transport, etc). Moreover, we
      characterized 1052 thioredoxin-dependent regulatory sites and showed that these
      data constitute a valuable resource for future functional studies in
      Chlamydomonas. By comparing this thioredoxome with proteomic data for
      glutathionylation and nitrosylation at the protein and cysteine levels, this work
      confirms the existence of a complex redox regulation network in Chlamydomonas and
      provides evidence of a tremendous selectivity of redox post-translational
      modifications for specific cysteine residues.

PMID- 28739496
TI  - Overexpression of Rabl3 and Cullin7 is associated with pathogenesis and poor
      prognosis in hepatocellular carcinoma.
AB  - The expression of Rabl3 and Cullin7 is relevant to the carcinogenesis of certain
      cancers. However, the relationship of this expression with hepatocellular
      carcinoma remains unclear. To study the protein expression of Rabl3 and Cullin7
      and to evaluate their role in hepatocarcinogenesis, in 162 cases of
      hepatocellular carcinoma, we used immunohistochemistry to investigate the
      expression of Rabl3 and Cullin7 in both the cancer tissues and the normal hepatic
      tissues around the hepatocellular carcinoma. The results demonstrated that the
      rates of positive Rabl3 and Cullin7 expression were 80.2% and 69.1%,
      respectively, in hepatocellular carcinoma tissues. However, the rates of positive
      Rabl3 and Cullin7 expression were 31.5% and 29.0%, respectively, in adjacent
      normal hepatic tissues. Rabl3 and Cullin7 were expressed at significantly higher
      rates in hepatocellular carcinoma compared with adjacent normal hepatic tissues
      (P<.01). The rates of positive Rabl3 and Cullin7 expression were higher in the
      hepatocellular carcinoma tissues of patients with lymph node metastasis, tumor
      thrombi in the portal vein and an advanced clinical stage (P<.05). A positive
      correlation between the expression of Rabl3 and the expression of Cullin7
      (r=0.27, P<.001) was also observed in our hepatocellular carcinoma cohort.
      Moreover, patients with positive expression for both Rabl3 and Cullin7 had a
      remarkably shorter survival time compared with patients with negative expression
      for both proteins (P<.05). Therefore, the expression of the Rabl3 and Cullin7
      proteins may play an important role in the pathogenesis and progression of
      hepatocellular carcinoma and could be used as a prognostic indicator in patients
      with hepatocellular carcinoma.

PMID- 28739497
TI  - Salivary gland epithelial neoplasms in pediatric population: a single-institute
      experience with a focus on the histologic spectrum and clinical outcome.
AB  - Salivary gland epithelial neoplasms are rare in children and adolescents, with
      only a handful of large series having been published. A retrospective study was
      conducted for 57 cases in patients 20 years or younger. The tumors were located
      in the parotid (n=36), submandibular gland (n=7), and minor salivary glands
      (n=14). Nineteen (33%) tumors were pleomorphic adenoma, whereas the remaining
      (67%) were malignant. The histologic types of carcinomas were mucoepidermoid
      carcinoma (MEC, n=19, 33%), acinic cell carcinoma (n=7, 12%), adenoid cystic
      carcinoma (n=6, 11%), secretory carcinoma (mammary analogue) (SC, n=4, 7%), and
      myoepithelial carcinoma (n=2, 4%). Ninety-three percent (13/14) of the minor and
      58% (25/43) of the major salivary gland tumors were malignant. A 7-year-old girl
      (2%) with a high-grade MEC died from her disease because of uncontrollable
      locoregional recurrence. Seven patients (16%) developed recurrence including 2
      distant metastases from adenoid cystic carcinoma and 6 locoregional recurrences
      (2 pleomorphic adenomas, 1 SC, 1 myoepithelial carcinoma, 1 adenoid cystic
      carcinoma, and 1 MEC). The following parameters were associated with decreased
      disease-free survival in malignant tumors: elevated mitotic index of >4/10 high
      power fields (log-rank test, P<.001), and advanced American Joint Committee on
      Cancer pT (P=.029) and pN stage (P<.001). In conclusion, myoepithelial carcinoma
      and SC can occur in the pediatric population and should be considered in the
      differential diagnosis. Salivary gland malignancies in children appear to have
      better clinical outcome, associated with a 10-year recurrence-free survival rate
      of 74% and a 10-year disease-specific survival of 94%.

PMID- 28739498
TI  - Increased expression of EZH2 in Merkel cell carcinoma is associated with disease
      progression and poorer prognosis.
AB  - Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects
      tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare
      cutaneous neuroendocrine carcinoma that has a high risk of disease progression
      with nodal and distant metastases. Here, we evaluated EZH2 expression by
      immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph
      node metastases, 13 in-transit metastases, and 2 distant metastases) with
      clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors.
      Importantly, weak expression of EZH2 in the primary tumor, but not nodal
      metastases, correlated with improved prognosis compared to moderate/strong EZH2
      expression (5-year MCC-specific survival of 68% versus 22%, respectively,
      P=.024). In addition, EZH2 was expressed at higher levels in nodal metastases
      compared to primary tumors (P=.005). Our data demonstrate that EZH2 has
      prognostic value and may play an oncogenic role in MCC.

PMID- 28739499
TI  - Primary signet ring stromal tumor of the testis: a study of 13 cases indicating
      their phenotypic and genotypic analogy to pancreatic solid pseudopapillary
      neoplasm.
AB  - Primary signet ring stromal tumor of the testis (PSRSTT) is an extremely rare
      tumor described only twice in the literature. Pancreatic-analogue solid
      pseudopapillary neoplasm (SPN) of the testis is a recently reported entity with
      morphological overlap with PSRSTT. We reviewed our files to find all cases of
      PSRSTT to better characterize this entity. We studied 13 cases of PSRSTTs using
      histological, immunohistochemical (IHC), and molecular genetic methods and
      compared the results with pancreatic SPN. Grossly, the size of PSRSTTs ranged
      from 0.5 to 2 cm (mean 1.1). Microscopically, PSRSTTs predominantly showed a
      proliferation of low-grade epithelioid cells containing characteristic
      cytoplasmic vacuole dislodging the nucleus (signet ring cells) separated by
      fibrous septa into trabeculae and nests. The immunoprofile was characterized by
      immunoreactivity for beta-catenin, cyclin D1 (nuclear positivity for both
      antibodies), CD10, vimentin, galectin-3, claudin 7, alpha-1-antitrypsin, CD56,
      and neuron-specific enolase and negativity for chromogranin, inhibin, calretinin,
      SF-1, NANOG, OCT3/4, and SALL4. In some cases, the IHC panel was restricted
      because of a limited amount of tissue. Molecular genetic analysis revealed
      mutations within exon 3 of the CTNNB1 encoding beta-catenin in all analyzable
      cases. Based on histological similarities between pancreatic SPN and PSRSTT and
      their identical IHC and molecular genetic features, we assume that both neoplasms
      share the same pathogenesis, and thus, PSRSTT can be considered as a testicular
      analogue of pancreatic SPN.

PMID- 28739500
TI  - Breast implant capsule-associated squamous cell carcinoma: a report of 2 cases.
AB  - The use of prosthetic implants for breast augmentation has become commonplace.
      Although implants do not increase the risk of conventional mammary carcinoma,
      they are rarely associated with anaplastic large cell lymphoma. We report 2 cases
      of breast implant capsule-associated squamous cell carcinoma with poor clinical
      outcomes. Both patients (56-year-old woman and 81-year-old woman) had long
      standing implants (>25 years) and presented with acute unilateral breast
      enlargement. In both cases, squamous cell carcinoma arose in (focally dysplastic)
      squamous epithelium-lined breast implant capsules and widely invaded surrounding
      breast parenchyma or chest wall. Neither patient had evidence of a primary
      mammary carcinoma or squamous cell carcinoma at any other anatomic site. Within 1
      year, one patient developed extensive, treatment-refractory, locoregional soft
      tissue metastasis, and the second patient developed hepatic and soft tissue
      metastases and died of disease. There are 2 prior reported cases of implant
      associated squamous cell carcinoma in the plastic surgery literature; one
      provides no pathologic staging or outcome information, and the second case was a
      capsule-confined squamous cell carcinoma. Together, all 4 cases share notable
      commonalities: the patients had long-standing breast implants and presented with
      acute unilateral breast pain and enlargement secondary to tumors arising on the
      posterior aspect of squamous epithelialized implant capsules. Because of both its
      rarity and its unusual clinical presentation, implant capsule-associated squamous
      cell carcinoma may be underrecognized. The aggressive behavior of the tumors in
      this series underscores the importance of excluding malignancy in patients with
      long-standing breast implants who present with acute unilateral breast pain and
      enlargement.

PMID- 28739501
TI  - Shear-responsive injectable supramolecular hydrogel releasing doxorubicin loaded
      micelles with pH-sensitivity for local tumor chemotherapy.
AB  - In this study, glycol chitosan-Pluronic F127 conjugate (GC-PF127), produced by an
      amidation reaction between terminal-carboxylated PF127 and glycol chitosan (GC),
      was used to prepare doxorubicin (DOX)-loaded micelles. The DOX/GC-PF127 micelles
      produced at optimal conditions had sizes of about 150nm and pH-sensitive surface
      charges. DOX/GC-PF127 hydrogel formed after addition of alpha-cyclodextrin into
      DOX/GC-PF127 micelle solution. The hydrogel had good shear-responsive, injectable
      and rapid recovery properties. In vitro release experiment confirmed that the
      hydrogel could sustainedly release DOX/GC-PF127 micelles via the dissociation of
      the hydrogel. After peritumoral injection into H22 tumor-bearing mice, the
      hydrogel could greatly increase DOX accumulation in tumor tissue and
      synchronously avoid DOX accumulation in normal tissues including heart. At
      similar total DOX dose administrated, the tumors of free DOX treatment group grew
      slowly after thrice intravenous injections, the tumors of the micelle group did
      not grow after twice intravenous injections, and the tumors of the hydrogel group
      disappeared almost after once peritumoral injection. This study demonstrates that
      injectable DOX/GC-PF127 hydrogel, which can sustainedly release DOX-loaded
      micelles with tumor-targeting function, is a promising system for local tumor
      chemotherapy.

PMID- 28739502
TI  - Development of biomedical 5-fluorouracil nanoplatforms for colon cancer
      chemotherapy: Influence of process and formulation parameters.
AB  - In the present investigation solvent displacement or nanoprecipitation, and
      emulsion/solvent evaporation methods were utilized to optimize poly(D,L-lactide
      co-glycolide) nanoparticles for the vehiculization of the 5-fluorouracil.
      Formulation components from both the aqueous and organic phases, as well as,
      operating conditions were varied. Particles were characterized in terms of
      particle size and morphology, electrical properties, rheology, drug loading,
      stability, and drug release. Furthermore, in vitro cytotoxicity on human colon
      cells and different colon carcinoma cells was evaluated. Four types of
      nanoparticles were selected for drug loading, revealing differences between
      variables. Low viscosity values and their Newtonian behavior could assure the
      suitability of the nanoformulation for the intravenous route of administration.
      The greatest drug entrapment efficiency and best stability was achieved when the
      chemotherapeutic agent was incorporated into the internal aqueous phase of
      particles prepared by double emulsion/solvent evaporation. However, a more
      sustained drug release at pH 7.4 was possible when 5-fluorouracil was added to
      the external aqueous phase. These were the nanoformulations reporting the
      greatest antiproliferative efficacy compared with the free drug. The nanocarrier
      can optimize the antitumor activity of 5-fluorouracil, thus being a potential
      nanotool against colon cancer.

PMID- 28739503
TI  - Improved transdermal delivery of morin efficiently inhibits allergic contact
      dermatitis.
AB  - The skin is an important site for local or systemic application of drugs.
      However, most of the drugs have poor permeability through the skin's outermost
      layer, stratum corneum. The aim of this study was to develop a method to enable
      transdermal delivery of morin (3, 5, 7, 2, 4-pentahydroxyflavone), which is a
      poorly water-soluble drug with anti-inflammatory properties obtained from natural
      products. Morin phospholipid complex (MPC) was prepared and then loaded in
      Carbopol 940 hydrogel (MPC-gel), which can significantly increase the transdermal
      flux of morin based on the in vitro skin penetration data presented in this
      paper. To further enhance permeation, different compositions of penetration
      enhancers were dispersed in the gel and screened. After applied onto the mouse
      skin, MPC-gel showed apparent reduction of ear swelling in 2, 4
      dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD). Further
      determination of cytokines levels, histopathological analysis and T lymphocytes
      proliferation indicates that the MPC-gel is potent enough to reduce the
      inflammatory response mediated by the DNFB in ACD mice model. Collectively, we
      anticipate that such an approach may provide a new treatment for topical ACD.

PMID- 28739504
TI  - Improved metabolic stability and therapeutic efficacy of a novel molecular
      gemcitabine phospholipid complex.
AB  - The aim of the present research is to increase lipid solubility, metabolic
      stability and therapeutic efficacy of water soluble gemcitabine (GEM) via
      phospholipid complex (PC) formation. A novel phospholipid complex of GEM was
      successfully prepared and optimized. Physical interaction of GEM with
      phospholipid was evaluated by DSC, FT-IR, 1H NMR, 31P-NMR and P-XRD. SEM images
      of GEM-PC showed rough structure and TEM images of diluted aqueous dispersion of
      GEM-PC showed micellar structure. In silico study also revealed the significant
      interaction between drug and phospholipid. GEM-PC demonstrated sustained drug
      release pattern and high plasma stability (~2.2 fold) in vitro as compared to
      GEM. Increased in vitro cytotoxicity and apoptosis were observed with GEM-PC,
      when incubated with human pancreas adenocarcinoma cell lines. In vivo
      pharmacokinetics showed the almost 2 fold increase in AUC0-infinity (area under
      curve) with phospholipid complex (8983.26ngh/ml) as compared with GEM
      (4371.18ngh/ml) and GEMITA (4689.29ngh/ml). Toxicity studies signify the safety
      of GEM-PC over GEMITA. Pharmacodynamics studies in pancreatic tumor model further
      revealed higher efficacy of GEM-PC than GEMITA. These findings suggested the
      higher potential of phospholipid based technology for the enhancement of
      metabolic stability and therapeutic efficacy of GEM.

PMID- 28739505
TI  - Valorisation of softwood bark through extraction of utilizable chemicals. A
      review.
AB  - Softwood bark is an important source for producing chemicals and materials as
      well as bioenergy. Extraction is regarded as a key technology for obtaining
      chemicals in general, and valorizing bark as a source of such chemicals in
      particular. In this paper, properties of 237 compounds identified in various
      studies dealing with extraction of softwood bark were described. Finally, some
      challenges and perspectives on the production of chemicals from bark are
      discussed.

PMID- 28739506
TI  - Glycosaminoglycans from marine sources as therapeutic agents.
AB  - Glycosaminoglycans (GAGs) in marine animals are different to those of terrestrial
      organisms, mainly in terms of molecular weight and sulfation. The therapeutic
      properties of GAGs are related to their ability to interact with proteins, which
      is very much influenced by sulfation position and patterns. Since currently GAGs
      cannot be chemically synthesized, they are sourced from natural products, with
      high intra- but also inter-species variability, in terms of chain length,
      disaccharide composition and sulfation pattern. Consequently, sulfated GAGs are
      the most interesting molecules in the marine environment and constitute the focus
      of the present review. In particular, chondroitin sulfate (CS) appears as the
      most promising compound. CS-E chains [GlcA-GalNAc(4S,6S)] extracted from squid
      possess antiviral and anti-metastatic activities and seem to impart signalling
      properties and improve the mechanical performance of cartilage engineering
      constructs; Squid CS-E and octopus CS-K [GlcA(3S)-GalNAc(4S)], dermatan sulfate
      (DS) from sea squirts [-iK units, IdoA(3S)-GalNAc(4S)] and sea urchins [-iE
      units, IdoA-GalNAc(4S,6S)] and hybrids CS/DS from sharks (-B/iB [GlcA/IdoA(2S)
      GalNAc(4S)], -D/iD [GlcA/IdoA(2S)-GalNAc(6S)] and -E/iE units [GlcA/IdoA
      GalNAc(4S,6S)]) promote neurite outgrowth and could be valuable materials for
      nerve regeneration. Also displaying antiviral and anti-metastatic properties, a
      rare CS with fucosylated branches isolated from sea cucumbers is an anticoagulant
      and anti-inflammatory agent. In this same line, marine heparin extracted from
      shrimp and sea squirt has proven anti-inflammatory properties, with the added
      advantage of decreased risk of bleeding because of its low anticoagulant
      activity.

PMID- 28739507
TI  - Neuroactive steroids and diabetic complications in the nervous system.
AB  - Important complications of diabetes mellitus in the nervous system are
      represented by diabetic peripheral neuropathy and diabetic encephalopathy. In
      this context, an important link is represented by neuroactive steroids (i.e.,
      steroids coming from peripheral glands and affecting nervous functionality as
      well as directly synthesized in the nervous system). Indeed, diabetes does not
      only affect the reproductive axis and consequently the levels of sex steroid
      hormones, but also those of neuroactive steroids. Indeed, as will be here
      summarized, the levels of these neuromodulators present in the central and
      peripheral nervous system are affected by the pathology in a sex-dimorphic way.
      In addition, some of these neuroactive steroids, such as the metabolites of
      progesterone or testosterone, as well as pharmacological tools able to increase
      their levels have been demonstrated, in experimental models, to be promising
      protective agents against diabetic peripheral neuropathy and diabetic
      encephalopathy.

PMID- 28739508
TI  - Endocannabinoids: Effectors of glucocorticoid signaling.
AB  - For decades, there has been speculation regarding the interaction of cannabinoids
      with glucocorticoid systems. Given the functional redundancy between many of the
      physiological effects of glucocorticoids and cannabinoids, it was originally
      speculated that the biological mechanisms of cannabinoids were mediated by direct
      interactions with glucocorticoid systems. With the discovery of the
      endocannabinoid system, additional research demonstrated that it was actually the
      opposite; glucocorticoids recruit endocannabinoid signaling, and that the
      engagement of endocannabinoid signaling mediated many of the neurobiological and
      physiological effects of glucocorticoids. With the development of advances in
      pharmacology and genetics, significant advances in this area have been made, and
      it is now clear that functional interactions between these systems are critical
      for a wide array of physiological processes. The current review acts a
      comprehensive summary of the contemporary state of knowledge regarding the
      biological interactions between glucocorticoids and endocannabinoids, and their
      potential role in health and disease.

PMID- 28739509
TI  - Proteomic analysis of the secretome of human bone marrow-derived mesenchymal stem
      cells primed by pro-inflammatory cytokines.
AB  - Mesenchymal stem cells (MSC) represent an impressive opportunity in term of
      regenerative medicine and immunosuppressive therapy. Although it is clear that
      upon transplantation MSC exert most of their therapeutic effects through the
      secretion of bioactive molecules, the effects of a pro-inflammatory recipient
      environment on MSC secretome have not been characterized. In this study, we used
      a label free mass spectrometry based quantitative proteomic approach to analyze
      how pro-inflammatory cytokines modulate the composition of the human MSC
      secretome. We found that pro-inflammatory cytokines have a strong impact on the
      secretome of human bone marrow-derived MSC and that the large majority of
      cytokine-induced proteins are involved in inflammation and/or angiogenesis.
      Comparative analyses with results recently obtained on mouse MSC secretome
      stimulated under the same conditions reveals both analogies and differences in
      the effect of pro-inflammatory cytokines on MSC secretome in the two organisms.
      In particular, functional analyses confirmed that tissue inhibitor of
      metalloproteinase-1 (TIMP1) is a key effector molecule responsible for the anti
      angiogenic properties of both human and mouse MSC within an inflammatory
      microenvironment. Mass spectrometry data are available via ProteomeXchange with
      identifier PXD005746 SIGNIFICANCE: The secretion of a broad range of bioactive
      molecules is believed to be the main mechanism by which MSC exert specific
      therapeutic effects. MSC are very versatile and respond to specific environments
      by producing and releasing a variety of effector molecules. To the best of our
      knowledge this is the first study aimed at describing the secretome of human MSC
      primed using a mixture of cytokines, to mimic pro-inflammatory conditions
      encountered in vivo, by a quantitative high-resolution mass spectrometry based
      approach. The main output of the study concerns the identification of a list of
      specific proteins involved in inflammation and angiogenesis which are
      overrepresented in stimulated MSC secretome. The data complement a previous study
      on the secretome of mouse MSC stimulated under the same conditions. Comparative
      analyses reveal analogies and differences in the biological processes affected by
      overrepresented proteins in the two organisms. In particular, the key role of
      TIMP-1 for the anti-angiogenic properties of stimulated MSC secretome already
      observed in mouse is confirmed in human. Overall, these studies represent key
      steps necessary to characterize the different biology of MSC in the two organisms
      and design successful pre-clinical experiments as well as clinical trials.

PMID- 28739510
TI  - Differential proteomics reveals S100-A11 as a key factor in aldosterone-induced
      collagen expression in human cardiac fibroblasts.
AB  - : Aldosterone (Aldo) could induce cardiac fibrosis, a hallmark of heart disease.
      Aldo direct effects on collagen production in cardiac fibroblasts remain
      controversial. Our aim is to characterize changes in the proteome of adult human
      cardiac fibroblasts treated with Aldo to identify new proteins altered that might
      be new therapeutic targets in cardiovascular diseases. Aldo increased collagens
      expressions in human cardiac fibroblasts. Complementary, using a quantitative
      proteomic approach, 30 proteins were found differentially expressed between
      control and Aldo-treated cardiac fibroblasts. Among these proteins, 7 were up
      regulated and 23 were down-regulated by Aldo. From the up-regulated proteins,
      collagen type I, collagen type III, collagen type VI and S100-A11 were verified
      by Western blot. Moreover, protein interaction networks revealed a functional
      link between a third of Aldo-modulated proteome and specific survival routes.
      S100-A11 was identified as a possible link between Aldo and collagen.
      Interestingly, CRISPR/Cas9-mediated knock-down of S100-A11 blocked Aldo-induced
      collagen production in human cardiac fibroblasts. In adult human cardiac
      fibroblasts treated with Aldo, proteomic analyses revealed an increase in
      collagen production. S100-A11 was identified as a new regulator of Aldo-induced
      collagen production in human cardiac fibroblasts. These data could identify new
      candidate proteins for the treatment of cardiac fibrosis in cardiovascular
      diseases. SIGNIFICANCE: S100-A11 is identified by a proteomic approach as a novel
      regulator of Aldosterone-induced collagen production in human cardiac
      fibroblasts. Our data could identify new candidate proteins of interest for the
      treatment of cardiac fibrosis in cardiovascular diseases.

PMID- 28739511
TI  - Revisiting venom of the sea anemone Stichodactyla haddoni: Omics techniques
      reveal the complete toxin arsenal of a well-studied sea anemone genus.
AB  - : More than a century of research on sea anemone venoms has shown that they
      contain a diversity of biologically active proteins and peptides. However, recent
      omics studies have revealed that much of the venom proteome remains unexplored.
      We used, for the first time, a combination of proteomic and transcriptomic
      techniques to obtain a holistic overview of the venom arsenal of the well-studied
      sea anemone Stichodactyla haddoni. A purely search-based approach to identify
      putative toxins in a transcriptome from tentacles regenerating after venom
      extraction identified 508 unique toxin-like transcripts grouped into 63 families.
      However, proteomic analysis of venom revealed that 52 of these toxin families are
      likely false positives. In contrast, the combination of transcriptomic and
      proteomic data enabled positive identification of 23 families of putative toxins,
      12 of which have no homology known proteins or peptides. Our data highlight the
      importance of using proteomics of milked venom to correctly identify venom
      proteins/peptides, both known and novel, while minimizing false positive
      identifications from non-toxin homologues identified in transcriptomes of venom
      producing tissues. This work lays the foundation for uncovering the role of
      individual toxins in sea anemone venom and how they contribute to the
      envenomation of prey, predators, and competitors. BIOLOGICAL SIGNIFICANCE:
      Proteomic analysis of milked venom combined with analysis of a tentacle
      transcriptome revealed the full extent of the venom arsenal of the sea anemone
      Stichodactyla haddoni. This combined approach led to the discovery of 12 entirely
      new families of disulfide-rich peptides and proteins in a genus of anemones that
      have been studied for over a century.

PMID- 28739512
TI  - Modulation of mitochondrial dysfunction-related oxidative stress in fibroblasts
      of patients with Leigh syndrome by inhibition of prooxidative p66Shc pathway.
AB  - The mitochondrial respiratory chain, and in particular, complex I, is a major
      source of reactive oxygen species (ROS) in cells. Elevated levels of ROS are
      associated with an imbalance between the rate of ROS formation and the capacity
      of the antioxidant defense system. Increased ROS production may lead to oxidation
      of DNA, lipids and proteins and thus can affect fundamental cellular processes.
      The aim of this study was to investigate the magnitude of intracellular oxidative
      stress in fibroblasts of patients with Leigh syndrome with defined mutations in
      complex I. Moreover, we hypothesized that activation of the p66Shc protein
      (phosphorylation of p66Shc at Ser36 by PKCbeta), being part of the oxidative
      stress response pathway, is partially responsible for the increased ROS
      production in cells with dysfunctional complex I. Characterization of
      bioenergetic parameters and ROS production showed that the cellular model of
      Leigh syndrome is described by increased intracellular oxidative stress and
      oxidative damage to DNA and proteins, which correlate with increased p66Shc
      phosphorylation at Ser36. Treatment of patient s' fibroblasts with hispidin (an
      inhibitor of the protein kinase PKCbeta), in addition to decreasing ROS
      production and intracellular oxidative stress, resulted in restoration of complex
      I activity.

PMID- 28739513
TI  - Intrauterine inflammation induces sex-specific effects on neuroinflammation,
      white matter, and behavior.
AB  - Exposure to inflammation during pregnancy has been linked to adverse
      neurodevelopmental consequences for the offspring. One common route through which
      a developing fetus is exposed to inflammation is with intrauterine inflammation.
      To that end, we utilized an animal model of intrauterine inflammation (IUI;
      intrauterine lipopolysaccharide (LPS) administration, 50ug, E15) to assess
      placental and fetal brain inflammatory responses, white matter integrity, anxiety
      related behaviors (elevated zero maze, light dark box, open field), microglial
      counts, and the CNS cytokine response to an acute injection of LPS in both males
      and females. These studies revealed that for multiple endpoints (fetal brain
      cytokine levels, cytokine response to adult LPS challenge) male IUI offspring
      were uniquely affected by intrauterine inflammation, while for other endpoints
      (behavior, microglial number) both sexes were similarly affected. These data
      advance our understanding of sex-specific effects of early life exposure to
      inflammation in a translationally- relevant model.

PMID- 28739514
TI  - Inhibition of blood-brain barrier efflux transporters promotes seizure in
      pregnant rats: Role of circulating factors.
AB  - Seizure-provoking factors circulate late in gestation during normal pregnancy,
      but do not readily gain access to the brain due to the protective nature of the
      blood-brain barrier. In particular, efflux transporters are powerful ATP-driven
      pumps that actively prevent unwanted compounds from entering the brain. We
      hypothesized that acute inhibition of efflux transporters at the blood-brain
      barrier would result in spontaneous seizures in pregnant rats. We further
      hypothesized that the blood-brain barrier protects the maternal brain from
      seizure by increasing expression and/or activity of p-glycoprotein (P-gp), a
      major efflux transporter. Main blood-brain barrier efflux transporters were
      inhibited in-vivo in nonpregnant (Nonpreg) and pregnant (Preg; d19) Sprague
      Dawley rats (n=8/group). Seizures were monitored in conscious animals for 8h via
      chronically implanted electroencephalography (EEG) electrodes in the hippocampus
      and motor cortex and time-synced video. P-gp activity was measured via a calcein
      accumulation assay in freshly isolated cortical and hippocampal capillaries from
      Preg (d20) and Nonpreg rats (n=8-16/group), to assess regional susceptibility to
      transporter inhibition. P-gp expression, capillary density, and microglial
      activation as a measure of neuroinflammation were quantified using
      immunohistochemistry (n=4-6/group). Efflux transporter inhibition elicited
      hippocampal seizures within 1h in 100% of Preg rats that was not associated with
      neuroinflammation or elevated tumor necrosis factor alpha (TNFalpha) or vascular
      endothelial growth factor (VEGF), but negatively correlated with levels of
      estradiol. Hippocampal seizures were considerably less prevalent in Nonpreg rats.
      However, behavioral seizures in the motor cortex developed of similar severity in
      both groups of rats, demonstrating regional heterogeneity in response to efflux
      transporter inhibition. Basal P-gp activity was similar between groups, however,
      exposure to serum from Preg rats significantly decreased P-gp activity in the
      hippocampus, but not cortex, compared to serum from Nonpreg rats (0.29+/
      0.1units/s in Preg vs. 0.06+/-0.02units/s in Nonpreg rats; p<0.05) that was not
      associated with elevated TNFalpha or VEGF. Thus, pregnancy differentially
      increased the susceptibility of the hippocampus to seizures in response to blood
      brain barrier efflux transporter inhibition that may be due to the inhibitory
      effect of circulating factors in pregnancy on P-gp activity in the hippocampus.

PMID- 28739515
TI  - The Trigeminocardiac Reflex During the Anterior Transpetrosal Approach.
AB  - OBJECTIVE: The anterior transpetrosal approach (ATPA), during which the
      trigeminal nerve (TN) is manipulated, has a risk of eliciting the
      trigeminocardiac reflex (TCR). The aim of this study was to assess the risk of
      TCR during ATPA. METHODS: Surgical records of 92 patients who had surgical
      treatment via ATPA at the Keio University Hospital between December 2005 and June
      2015 were retrospectively analyzed. Patients were divided into 2 groups on the
      basis of the occurrence of TCR during surgery, and clinical and tumor
      characteristics were compared. Tumor characteristics were evaluated based on
      preoperative images and intraoperative findings and included the side of the
      lesion, size of the lesion, tumor size in Meckel cave, pathology of the disease,
      cavernous sinus invasion, extension into Meckel cave, and adhesion of lesion to
      TN. RESULTS: TCR was observed in 14 of 92 patients (15.2%). TCR occurrence was
      significantly related to Meckel cave tumor size (P = 0.0264) and adhesion of the
      lesion to TN (P = 0.0002). CONCLUSIONS: This study suggests that TCR is related
      to Meckel cave tumor size and tumor adhesion to TN in ATPA. To our knowledge,
      this is the first report describing TCR during ATPA.

PMID- 28739516
TI  - Endopelvic Approach for Iliac Crest Bone Harvesting.
AB  - BACKGROUND: The anterior approach to lumbar spine surgery has grown in popularity
      in the past few years; spinal fusion of the last 2 lumbar levels is often
      required. Although alternatives to bone grafting are available, including
      recombinant human bone morphogenetic protein 2 or bone substitutes, only
      cancellous autologous bone has all the required factors for bone growth. To avoid
      the use of bone substitutes, remote iliac crest bone harvesting remains the gold
      standard. However, this technique may lead to some unfavorable outcomes. CASE
      DESCRIPTION: The patient was a 46-year-old man with severe back and left leg
      pain. Magnetic resonance imaging showed an inflammatory discopathy of L5-S1
      associated with a left posterior lateral herniated disc. Conservative treatment
      failed, and surgical treatment of the lumbar disk disease and the herniated disc
      was scheduled. A novel iliac crest bone harvesting method was performed during
      the retroperitoneal approach to the anterior lumbar interbody fusion. The
      patient's postoperative course was uneventful. There were no adverse outcomes
      related to the bone donor site. CONCLUSIONS: This is the first in vivo report of
      endopelvic iliac crest bone harvesting. This technique allows bone graft
      harvesting to be performed with the same retroperitoneal approach used for
      anterior lumbar interbody fusion. It avoids many common complications associated
      with the remote approach to the iliac crest.

PMID- 28739517
TI  - Novel Use of the Leksell Gamma Frame for Stereotactic Biopsy of Posterior Fossa
      Lesions.
AB  - BACKGROUND: Stereotactic transcerebellar biopsies of brainstem tumors have often
      been reported. The Leksell frame or Cosman-Roberts-Wells frame is often used in
      transcerebellar approaches. However, to access lesions via the cerebellum, these
      frames should be secured as inferiorly on the cranium as possible, which can
      require exaggerated neck flexion and limit the flexible trajectory to the target.
      To overcome these disadvantages, we have devised a new way to use the Leksell
      frame for transcerebellar approaches. METHODS: The frame was fixed to the upper
      part of the head and arc support by attaching the frame upside down, which gives
      surgeons a wide operative field and permits flexible trajectory planning.
      RESULTS: Under local anesthesia, the surgery was performed in a sitting position.
      Air was observed in the target site on postoperative computed tomography and
      magnetic resonance imaging, which confirmed that a specimen had been successfully
      sampled from the site as planned. CONCLUSIONS: Our devised transcerebellar
      approach provided a generous operative field and a flexible trajectory, which
      enabled minimally invasive biopsy of a posterior fossa lesions to be performed in
      a short amount of time with the patient under local anesthesia.

PMID- 28739518
TI  - Traumatic Brain Injury and Mood Stabilizers: Recent Cumulative Evidence.

PMID- 28739519
TI  - Bionic-Brain: Controlling a Prosthetic Hand.

PMID- 28739520
TI  - Clinical Observation of Posterior Percutaneous Full-Endoscopic Cervical
      Foraminotomy as a Treatment for Osseous Foraminal Stenosis.
AB  - OBJECTIVE: To observe the clinical effects of posterior percutaneous full
      endoscopic cervical foraminotomy in patients with osseous foraminal stenosis.
      METHODS: Nine patients with osseous foraminal stenosis underwent surgery using
      the posterior percutaneous full-endoscopic cervical foraminotomy technique and
      received follow-up care for 1 year. The visual analog scale score, neck
      disability index, and modified Macnab criteria were recorded at the last follow
      up. All patients underwent three-dimensional computed tomography of the cervical
      spine, which was reviewed within 1 week postoperatively. RESULTS: All operations
      were successful, and all patients received follow-up care. The mean operation
      time was 80 minutes. Surgical bleeding was not observed, and no related
      complications occurred. Postoperative visual analog scale and neck disability
      index scores were significantly reduced compared with the preoperative
      assessment. In addition, imaging showed that the osteophytes in the
      intervertebral foramen were adequately resected. According to modified Macnab
      criteria, 6 cases showed excellent results, 3 cases showed good results, and no
      fine or bad results were observed. CONCLUSIONS: Posterior percutaneous full
      endoscopic cervical foraminotomy can accomplish full nerve root decompression and
      is a safe, feasible procedure. Therefore, it can be a treatment option for
      patients with osseous foraminal stenosis.

PMID- 28739521
TI  - Effective Intraluminal Shunt in Carotid Endarterectomy for Carotid Artery Near
      Occlusion: Technical Report.
AB  - BACKGROUND: Carotid artery near occlusion is a critical degree of stenosis
      whereby blood flow is decreased and the distal cervical and intracranial internal
      carotid arteries (ICAs) are prone to collapse. Considering the diminished
      perfusion and risk of progression to total occlusion and periocclusive embolism,
      we performed carotid endarterectomy for carotid artery near occlusion. METHODS:
      Accurate evaluation of tandem stenosis or patency of the poststenotic ICA in
      carotid artery near occlusion is often difficult preoperatively. Thus we
      performed carotid endarterectomy in a hybrid operating room where intraoperative
      digital subtraction angiography (DSA) and endovascular angioplasty or stenting
      for distal lesions can be performed if necessary. In addition, to evaluate the
      distal ICA intraoperatively, we used an intraluminal shunt for shunt angiography,
      with injection of contrast material through the shunt tube, as a replacement for
      conventional DSA. Furthermore, an intraluminal shunt held the collapsed lumen
      open and provided a scaffold for suturing, which prevented postoperative stenosis
      of the distal ICA. CONCLUSION: The present report is intended to underline the
      merits of intraluminal shunt as a replacement for conventional DSA and as a
      scaffold for suturing.

PMID- 28739522
TI  - Bimodal odor processing with a trigeminal component at sub- and suprathreshold
      levels.
AB  - Odors are typically bimodal in nature, interacting with the olfactory and
      trigeminal systems. The trigeminal component may be noticed (e.g. menthol) or
      perceptually ignored, leading to different neural substrates being recruited
      during odor encoding. Therefore, the current study was designed to explore the
      perceptual and central-nervous activations in response to pleasant bimodal odors
      using functional magnetic resonance imaging (fMRI). In this study, healthy
      subjects were exposed to odorants alone (unimodal) or with a "cooling" trigeminal
      component (bimodal) at sub- and suprathreshold concentrations with a portable
      olfactometer in a 3T fMRI scanner. Within the scanner, subjects reported all
      odorants as pleasant and intensity increasing with trigeminal concentration. Many
      of the regions of interest [orbital frontal cortex (OFC), insula, thalamus,
      cerebellum, postcentral gyrus and cingulate cortex] were activated during bimodal
      odor conditions when contrasted with unimodal, and interestingly, most of these
      activations were seen prior to trigeminal perception (e.g. at a sub-threshold
      level). This includes large bilateral activations within the OFC, insula,
      cerebellum and parts of the cingulate cortex. Additionally, activation of the
      thalamus was seen early in the stages of bimodal odor encoding suggesting its
      role of mediating attention toward the presence of two stimuli. Lastly, intensity
      encoding during bimodal processing shows overlap of previously demonstrated
      simple trigeminal encoding areas (medial cingulate cortex) and the more complex
      olfactory encoding areas (bilateral insula, superior temporal gyrus, OFC, and
      cerebellum), but not the amygdala.

PMID- 28739523
TI  - Activity-dependent axonal plasticity in sensory systems.
AB  - The rodent whisker-to-barrel cortex pathway is a classic model to study the
      effects of sensory experience and deprivation on neuronal circuit formation, not
      only during development but also in the adult. Decades of research have produced
      a vast body of evidence highlighting the fundamental role of neuronal activity
      (spontaneous and/or sensory-evoked) for circuit formation and function. In this
      context, it has become clear that neuronal adaptation and plasticity is not just
      a function of the neonatal brain, but persists into adulthood, especially after
      experience-driven modulation of network status. Mechanisms for structural
      remodeling of the somatodendritic or axonal domain include microscale alterations
      of neurites or synapses. At the same time, functional alterations at the
      nanoscale such as expression or activation changes of channels and receptors
      contribute to the modulation of intrinsic excitability or input-output
      relationships. However, it remains elusive how these forms of structural and
      functional plasticity come together to shape neuronal network formation and
      function. While specifically somatodendritic plasticity has been studied in great
      detail, the role of axonal plasticity, (e.g. at presynaptic boutons, branches or
      axonal microdomains), is rather poorly understood. Therefore, this review will
      only briefly highlight somatodendritic plasticity and instead focus on axonal
      plasticity. We discuss (i) the role of spontaneous and sensory-evoked plasticity
      during critical periods, (ii) the assembly of axonal presynaptic sites, (iii)
      axonal plasticity in the mature brain under baseline and sensory manipulation
      conditions, and finally (iv) plasticity of electrogenic axonal microdomains,
      namely the axon initial segment, during development and in the mature CNS.

PMID- 28739524
TI  - Social instability stress in adolescent male rats reduces social interaction and
      social recognition performance and increases oxytocin receptor binding.
AB  - Social experiences in adolescence are essential for displaying context
      appropriate social behaviors in adulthood. We previously found that adult male
      rats that underwent social instability stress (SS) in adolescence had reduced
      social interactions with unfamiliar peers compared with non-stressed controls
      (CTL). Here we determined whether SS altered social recognition and social reward
      and brain oxytocin and vasopressin receptor density in adolescence. We confirmed
      that SS rats spent less time interacting with unfamiliar peers than did CTL rats
      (p=0.006). Furthermore, CTL rats showed a preference for novel over familiar
      conspecifics in a social recognition test whereas SS rats did not, which may
      reflect reduced recognition, impaired memory, or reduced preference for novelty
      in SS rats. The reward value of social interactions was not affected by SS based
      on conditioned place preference tests and based on the greater time SS rats spent
      investigating stimulus rats than did CTL rats when the stimulus rat was behind
      wire mesh (p=0.03). Finally, oxytocin receptor binding density was higher in the
      dorsal lateral septum and nucleus accumbens shell in SS rats compared with CTL
      rats (p=0.02, p=0.01, respectively). No effect of SS was found for vasopressin 1a
      receptor binding density in any of the brain regions analyzed. We discuss the
      extent to which the differences in social behavior exhibited after social
      instability in adolescence involve changes in social salience and social
      competency, and the possibility that changes in oxytocin signaling in the brain
      underlie the differences in social behavior.

PMID- 28739525
TI  - State-dependent alpha peak frequency shifts: Experimental evidence, potential
      mechanisms and functional implications.
AB  - Neural populations produce complex oscillatory patterns thought to implement
      brain function. The dominant rhythm in the healthy adult human brain is formed by
      alpha oscillations with a typical power peak most commonly found between 8 and
      12Hz. This alpha peak frequency has been repeatedly discussed as a highly
      heritable and stable neurophysiological "trait" marker reflecting anatomical
      properties of the brain, and individuals' general cognitive capacity. However,
      growing evidence suggests that the alpha peak frequency is highly volatile at
      shorter time scales, dependent on the individuals' "state". Based on the
      converging experimental and theoretical results from numerous recent studies,
      here we propose that alpha frequency variability forms the basis of an adaptive
      mechanism mirroring the activation level of neural populations which has
      important functional implications. We here integrate experimental and
      computational perspectives to shed new light on the potential role played by
      shifts in alpha peak frequency and discuss resulting implications. We further
      propose a potential mechanism by which alpha oscillations are regulated in a
      noisy network of spiking neurons in presence of delayed feedback.

PMID- 28739526
TI  - Chronic mild stress exacerbates severity of experimental autoimmune
      encephalomyelitis in association with altered non-coding RNA and metabolic
      biomarkers.
AB  - The causal factors determining the onset and severity of multiple sclerosis (MS)
      are not well understood. Here, we investigated the influence of chronic stress on
      clinical symptoms, metabolic and epigenetic manifestations of experimental
      autoimmune encephalomyelitis (EAE), a common animal model of MS. Lewis rats were
      immunized for monophasic EAE with MBP69-88 and were exposed to chronic stress for
      37days starting 7days prior to immunization. The exposure to stress accelerated
      and exacerbated the clinical symptoms of EAE. Both stress and EAE also disrupted
      metabolic status as indicated by trace elemental analysis in body hair. Stress
      particularly exacerbated chlorine deposition in EAE animals. Moreover, deep
      sequencing revealed a considerable impact of stress on microRNA expression in
      EAE. EAE by itself upregulated microRNA expression in lumbar spinal cord,
      including miR-21, miR-142-3p, miR-142-5p, miR-146a, and miR-155. Stress in EAE
      further up-regulated miR-16, miR-146a and miR-155 levels. The latter two
      microRNAs are recognized biomarkers of human MS. Thus, stress may synergistically
      exacerbate severity of EAE by altering epigenetic regulatory pathways. The
      findings suggest that stress may represent a significant risk factor for
      symptomatic deterioration in MS. Stress-related metabolic and microRNA signatures
      support their value as biomarkers for predicting the risk and severity of MS.

PMID- 28739527
TI  - Deconstructing the cortical column in the barrel cortex.
AB  - The question of what function is served by the cortical column has occupied
      neuroscientists since its original description some 60years ago. The answer seems
      tractable in the somatosensory cortex when considering the inputs to the cortical
      column and the early stages of information processing, but quickly breaks down
      once the multiplicity of output streams and their sub-circuits are brought into
      consideration. This article describes the early stages of information processing
      in the barrel cortex, through generation of the center and surround receptive
      field components of neurons that subserve integration of multi whisker
      information, before going on to consider the diversity of properties exhibited by
      the layer 5 output neurons. The layer 5 regular spiking (RS) neurons differ from
      intrinsic bursting (IB) neurons in having different input connections, plasticity
      mechanisms and corticofugal projections. In particular, layer 5 RS cells employ
      noise reduction and homeostatic plasticity mechanism to preserve and even
      increase information transfer, while IB cells use more conventional Hebbian
      mechanisms to achieve a similar outcome. It is proposed that the rodent analog of
      the dorsal and ventral streams, a division reasonably well established in primate
      cortex, might provide a further level of organization for RS cell function and
      hence sub-circuit specialization.

PMID- 28739528
TI  - Chronic hyper-leptinemia induces insulin signaling disruption in adipocytes:
      Implications of NOS2.
AB  - Leptin, following its discovery, has developed a formidable interest in the
      scientific community to delineate its contribution towards overall metabolic
      homeostasis. Contradictory reports have been published on leptin administration
      effects on whole body insulin sensitivity. Following late reports, we surveyed
      human serum leptin levels along with other metabolic parameters including BMI and
      HOMA-IR. We found a positive correlation between leptin levels and insulin
      resistance parameters. Considering the presence of the long form of leptin
      receptor on adipocytes, we explored the effects of chronic physiological hyper
      leptinemic exposure on adipocyte insulin sensitivity. Chronic leptin (50ng/ml)
      treatment in 3T3-L1 adipocytes decreased insulin-induced phosphorylation of nodal
      insulin signaling proteins along with reduced glucose uptake. Metabolic flux
      studies indicated mitochondrial dysfunction and reduced oxygen consumption rate.
      Leptin treatment also increased both cellular and mitochondrial superoxide levels
      concomitant to increased expression of nitric oxide synthase-2 (NOS2). Further,
      pharmacological depletion of NOS2 reversed leptin mediated effects on insulin
      signaling. In-vivo implantation of leptin osmotic pumps in C57BL/6 mice also
      decreased insulin responsiveness. Interestingly, these effects were lacking in
      NOS2 knockout strain. In conclusion, our studies put forward a potential link
      between leptin and adipocyte insulin responsiveness in an NOS2 dependent manner.

PMID- 28739529
TI  - Control of the NADPH supply for oxidative stress handling in cancer cells.
AB  - It has not been systematically analyzed whether the NADPH supply is a limiting
      factor for oxidative stress management in cancer cells. In the present work, it
      was determined in non-cancer and cancer cells the protein contents and kinetomics
      of (i) the cytosolic enzymes responsible for the NADPH production (i.e., Glc6PDH,
      6PGDH, ME, IDH-1); and (ii) the two main enzymes responsible for NADPH/NADP+ and
      GSH/GSSG recycling (GR, GPx-1) associated to oxidative stress management. With
      these data, kinetic models were built and further validated. Rat liver and
      hepatoma AS-30D cytosolic fractions exhibited greater Vmax for IDH-1 than for
      Glc6PDH and 6PGDH whereas human cancer cells and platelets showed greater Vmax
      for Glc6PDH than for 6PGDH and IDH-1. The ME activity was comparatively low in
      all cell types tested. The Km values for the respective specific substrates were
      all similar among the different cell types. Most activities were lower in AS-30D
      cells than in liver. In contrast, IDH-1, Glc6PDH and GR activities in human
      cancer cells were similar or greater to those of platelets, but GPx-1 activity
      was severely suppressed, despite showing similar GPx-1 protein content vs.
      platelets. Kinetic analysis and pathway modeling revealed a previously unveiled
      feedback IDH-1 regulation by GSH. The oxidative stress management in cancer cells
      (i) was mainly controlled by GPx-1 and the main NADPH provider was Glc6PDH; and
      (ii) modeling indicated that NADPH supply was not a controlling step. These data
      suggested that Glc6PDH and GPx-1 are adequate and promising targets for anti
      cancer therapeutic intervention.

PMID- 28739530
TI  - Curcumin modulates endothelial permeability and monocyte transendothelial
      migration by affecting endothelial cell dynamics.
AB  - Curcumin is a phenolic compound that exhibits beneficial properties for
      cardiometabolic health. We previously showed that curcumin reduced the
      infiltration of immune cells into the vascular wall and prevented atherosclerosis
      development in mice. This study aimed to investigate the effect of curcumin on
      monocyte adhesion and transendothelial migration (TEM) and to decipher the
      underlying mechanisms of these actions. Human umbilical vein endothelial cells
      (HUVECs) were exposed to curcumin (0.5-1MUM) for 3h prior to their activation by
      Tumor Necrosis Factor alpha (TNF-alpha). Endothelial permeability, monocyte
      adhesion and transendothelial migration assays were conducted under static
      condition and shear stress that mimics blood flow. We further investigated the
      impact of curcumin on signaling pathways and on the expression of genes using
      macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte
      adhesion and their transendothelial migration in both static and shear stress
      conditions. Curcumin also prevented changes in both endothelial permeability and
      the area of HUVECs when induced by TNF-alpha. We showed that curcumin modulated
      the expression of 15 genes involved in the control of cytoskeleton and
      endothelial junction dynamic. Finally, we showed that curcumin inhibited NF
      kappaB signaling likely through an antagonist interplay with several kinases as
      suggested by molecular docking analysis. Our findings demonstrate the ability of
      curcumin to reduce monocyte TEM through a multimodal regulation of the
      endothelial cell dynamics with a potential benefit on the vascular endothelial
      function barrier.

PMID- 28739531
TI  - Oxidative and ER stress-dependent ASK1 activation in steatotic hepatocytes and
      Kupffer cells sensitizes mice fatty liver to ischemia/reperfusion injury.
AB  - : Steatosis intensifies hepatic ischemia/reperfusion (I/R) injury increasing
      hepatocyte damage and hepatic inflammation. This study evaluates if this process
      is associated to a differential response of steatotic hepatocytes (HP) and
      Kupffer cells (KC) to I/R injury and investigates the molecular mechanisms
      involved. Control or steatotic (treated with 50 MUmol palmitic acid, PA) mouse HP
      or KC were exposed to hypoxia/reoxygenation (H/R). C57BL/6 mice fed 9 week with
      control or High Fat diet underwent to partial hepatic IR. PA increased H/R damage
      of HP and further activated the ASK1-JNK axis stimulated by ER stress during H/R.
      PA also induced the production of oxidant species (OS), and OS prevention
      nullified the capacity of PA to increase H/R damage and ASK1/JNK stimulation.
      ASK1 inhibition prevented JNK activation and entirely protected HP damage. In KC,
      PA directly activated ER stress, ASK1 and p38 MAPK and increased H/R damage.
      However, in contrast to HP, ASK1 inhibition further increased H/R damage by
      preventing p38 MAPK activation. In mice liver, steatosis induced the expression
      of activated ASK1 in only KC, whereas I/R exposure of steatotic liver activated
      ASK1 expression also in HP. "In vivo", ASK1 inhibition prevented ASK1, JNK and
      p38 MAPK activation and protected I/R damage and expression of inflammatory
      markers. CONCLUSIONS: Lipids-induced ASK1 stimulation differentially affects HP
      and KC by promoting cytotoxic or protective signals. ASK1 increases H/R damage of
      HP by stimulating JNK and protects KC activating p38MAPK. These data support the
      potentiality of the therapeutic employment of ASK1 inhibitors that can antagonize
      the damaging effects of I/R upon fatty liver surgery by the contextual reduction
      of HP death and of KC-mediated reactions.

PMID- 28739532
TI  - Denervated muscle fibers induce mitochondrial peroxide generation in neighboring
      innervated fibers: Role in muscle aging.
AB  - Disruption of neuromuscular junctions and denervation of some muscle fibers
      occurs in ageing skeletal muscle and contribute to loss of muscle mass and
      function. Aging is associated with mitochondrial dysfunction and loss of redox
      homeostasis potentially occurs through increased mitochondrial generation of
      reactive oxygen species (ROS). No specific link between increased mitochondrial
      ROS generation and denervation has been defined in muscle ageing. To address
      this, we have examined the effect of experimental denervation of all fibers, or
      only a proportion of the fibers, in the mouse tibialis anterior (TA) muscle on
      muscle mitochondrial peroxide generation. Transection of the peroneal nerve of
      mice caused loss of pre-synaptic axons within 1-3 days with no significant
      morphological changes in post-synaptic structures up to 10 days post-surgery when
      decreased TA mass and fiber size were apparent. Mitochondria in the denervated
      muscle showed increased peroxide generation by 3 days post-transection. Use of
      electron transport chain (ETC) substrates and inhibitors of specific pathways
      indicated that the ETC was unlikely to contribute to increased ROS generation,
      but monoamine oxidase B, NADPH oxidase and phospholipase enzymes were implicated.
      Transection of one of the 3 branches of the peroneal nerve caused denervation of
      some TA muscle fibers while others retained innervation, but increased
      mitochondrial peroxide generation occurred in both denervated and innervated
      fibers. Thus the presence of recently denervated fibers leads to increased ROS
      generation by mitochondria in neighboring innervated fibers providing a novel
      explanation for the increased mitochondrial oxidative stress and damage seen with
      aging in skeletal muscles.

PMID- 28739533
TI  - Effect of Bisphenol-A (BPA) on insulin signal transduction and GLUT4
      translocation in gastrocnemius muscle of adult male albino rat.
AB  - Environmental estrogens bind to estrogen receptors, mimic estrogenic actions, and
      have adverse effects on human health like Bisphenol - A (BPA) which is used as a
      monomer in the production of polycarbonate plastics (PC) and epoxy resins which
      are used in variety of canned foods. Skeletal muscle plays an essential role in
      maintaining systemic glucose metabolism. In the present study, we investigated
      the possible effects of BPA on insulin signalling molecules and GLUT4
      translocation in the gastrocnemius muscle of adult male rat. Rats were divided
      into four groups - Group I: Control (vehicle-corn oil treated), Group II, III and
      IV were administered with BPA (10, 100 and 400mg/kg b.wt/day, respectively)
      through oral gavage. Fasting blood glucose level of BPA treated groups showed a
      significant increase, oral glucose tolerance and insulin tolerance were also
      impaired in these animals. BPA significantly decreased the protein levels of
      insulin signalling molecules like IR, IRS-1, Akt, AS160 and its phosphorylated
      forms and blunts GLUT4 translocation by altering the levels of v- and t- SNARE
      proteins that assist the translocation process, thereby decreasing glucose uptake
      and oxidation in the gastrocnemius muscle. These results suggest that BPA has
      detrimental effects on insulin signalling molecules and GLUT4 translocation in
      the gastrocnemius muscle and thus impairs glucose homeostasis.

PMID- 28739534
TI  - Insurance Coverage and Well-Child Visits Improved for Youth Under the Affordable
      Care Act, but Latino Youth Still Lag Behind.
AB  - OBJECTIVE: To examine whether there have been changes in insurance coverage and
      health care utilization for youth before and after the national implementation of
      the Patient Protection and Affordable Care Act (ACA) and to assess whether racial
      and ethnic inequities have improved. METHODS: Data are from 64,565 youth (ages 0
      17 years) participants in the 2011 to 2015 National Health Interview Survey. We
      conducted multivariate logistic regression analyses to determine how the period
      after national implementation of the ACA (years 2011-2013 vs years 2014-2015) was
      associated with health insurance coverage and utilization of health care services
      (well-child visits, having visited an emergency department, and having visited a
      physician, all in the past 12 months), and whether changes over the pre- and post
      ACA periods varied according to race and Latino ethnicity. RESULTS: The post-ACA
      period was associated with improvements in insurance coverage and well-child
      visits for all youth. Latino youth had the largest absolute gain in insurance
      coverage; however, they continued to have the highest proportion of uninsurance
      post national ACA implementation. With regard to health care equity, non-Latino
      black youth were less likely to be uninsured and Latino youth had no significant
      improvements in insurance coverage relative to non-Latino white youth after
      national ACA implementation. Inequities in health care utilization for non-Latino
      black and Latino youth relative to non-Latino white youth did not improve.
      CONCLUSIONS: Insurance coverage and well-child visits have significantly improved
      for all youth since passage of the ACA, but inequities persist, especially for
      Latino youth.

PMID- 28739535
TI  - Importance and Feasibility of Transitional Care for Children With Medical
      Complexity: Results of a Multistakeholder Delphi Process.
AB  - BACKGROUND: Children with medical complexity (CMC) account for disproportionate
      hospital utilization and adverse outcomes after discharge, and several gaps exist
      regarding the quality of hospital to home transitional care for this population.
      We conducted an expert elicitation process to identify important and feasible
      hospital to home transitional care interventions for CMC from the perspectives of
      parents and health care professionals. METHODS: We conducted a 2-round electronic
      Delphi process to identify important and feasible transitional care
      interventions. Panelists included parents of CMC and multidisciplinary health
      care professionals. In the first round, panelists rated the importance and
      feasibility of 39 transitional care interventions on a 9-point Likert scale;
      agreement between panelists was defined according to RAND/UCLA Appropriateness
      Methods. The second round of data collection evaluated 16 interventions that
      panelists did not agree on in the first round and 8 new or revised interventions,
      accompanied by quantitative and qualitative data summaries. RESULTS: A total of
      29 parents of CMC and 37 health care professionals participated in the Delphi
      process (response rate 75%). Both stakeholder panels endorsed most interventions
      as important; health care professionals were less likely to rate several
      interventions as feasible compared with the parent panel. Over 2 rounds of data
      collection, the 2 stakeholder panels endorsed 25 interventions as important as
      well as feasible. These interventions related to family engagement during the
      hospitalization, care coordination and social support assessment, predischarge
      education, and written materials. CONCLUSIONS: Parents and health care
      professionals considered several transitional care interventions important as
      well as feasible. This research might inform hospitals' transitional care
      programs and policies.

PMID- 28739536
TI  - Time2bHealthy - An online childhood obesity prevention program for preschool-aged
      children: A randomised controlled trial protocol.
AB  - BACKGROUND: The use of parent-focused internet-based programs for the prevention
      and treatment of childhood obesity has shown promise but there is an acknowledged
      gap in parent-focused interventions which target the early childhood stage.
      METHODS: The aim of this study is to determine the efficacy of Time2bHealthy - an
      online healthy lifestyle program for parents of preschool-aged children. The
      program will be evaluated using a two-arm, parallel, randomised controlled
      design. The 11-week program is underpinned by Social Cognitive Theory and
      consists of interactive modules on healthy eating, physical activity, screen-time
      and sleep. The intervention also involves elements of social media, where
      participants share discuss ideas and experiences and they can interact and obtain
      information with experts. Time2bHealthy is being compared to a comparison
      condition. Outcomes include change in BMI (primary outcome), dietary intake,
      physical activity, sleep, child feeding, parental role-modelling and parent self
      efficacy. Process evaluation data, such as adherence and engagement with the
      online forums, will also be collected. DISCUSSION: Time2bHealthy is the first
      randomised controlled trial to our knowledge to assess the efficacy of an online
      parent-focussed healthy lifestyle program for preschool-aged children in changing
      body mass index. Early childhood is a crucial time for establishing healthy
      lifestyle behaviours and parents play an important role. This study therefore
      fills an important gap in the literature. If found to be efficacious,
      Time2bHealthy has potential for broad-reach access and translation into primary
      health care services. TRIAL REGISTRATION: The study is registered with the
      Australian and New Zealand Clinical Trials Registry (12616000119493).

PMID- 28739537
TI  - Differing antidepressant maintenance methodologies.
AB  - BACKGROUND: The principle evidence that antidepressant medication (ADM) is an
      effective maintenance treatment for adults with major depressive disorder (MDD)
      is from placebo substitution trials. These trials enter responders from ADM
      efficacy trials into randomized, double-blind placebo-controlled (RDBPC)
      effectiveness trials to measure the rate of MDD relapse over time. However, other
      randomized maintenance trial methodologies merit consideration and comparison.
      METHODS: A systematic review of ADM randomized maintenance trials included
      research reports from multiple databases. Relapse rate was the main effectiveness
      outcome assessed. RESULTS: Five ADM randomized maintenance methodologies for MDD
      responders are described and compared for outcome. These effectiveness trials
      include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs.
      psychotherapy, and treatment as usual. The placebo-substitution trials for those
      abruptly switched to placebo resulted in unusually high (46%) rates of relapse
      over 6-12months, twice the continuing ADM rate. These trials were characterized
      by selective screening, high attrition, an anxious anticipation of a switch to
      placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM
      efficacy responders who entered into 4-12month extension trials experienced
      relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored
      randomized trials of adults with multiple prior MDD episodes who were treated
      with ADM maintenance for 1-2years experienced relapse rates averaging 40%.
      CONCLUSIONS: Placebo substitution trial methodology represents only one approach
      to assess ADM maintenance. Antidepressant maintenance research for adults with
      MDD should be evaluated for industry sponsorship, attrition, the impact of the
      switch to placebo, and major relapse differences in MDD subpopulations.

PMID- 28739538
TI  - The implementation of prolonged exposure: Design of a multisite study evaluating
      the usefulness of workshop with and without consultation.
AB  - This randomized trial examines the dissemination and implementation of prolonged
      exposure (PE) therapy for posttraumatic stress symptoms in U.S. Army medical
      treatment facilities. The study compares two PE training models: Standard PE
      training, comprised of a 4-day workshop only, and Extended PE training, comprised
      of a 4-day workshop plus expert case consultation. Behavioral health providers
      (N=180) across three medium-to-large Army installations will be randomly assigned
      to either Standard PE training or Extended PE training. Changes in provider
      attitudes will be examined across groups. After completing PE training, the use
      of PE components with patients reporting posttraumatic stress symptoms and
      clinical outcomes of these participating patients (N=500) will be examined. This
      article describes the rationale and methods of the study. In addition, a number
      of methodological issues in conducting a multisite naturalistic study in the U.S.
      Army are discussed.

PMID- 28739539
TI  - Medication Reviews Bridging Healthcare (MedBridge): Study protocol for a
      pragmatic cluster-randomised crossover trial.
AB  - BACKGROUND: Mismanaged prescribing and use of medication among elderly puts major
      pressure on current healthcare systems. Performing a medication review, a
      structured critical examination of a patient's medications, during hospital stay
      with active follow-up into primary care could optimise treatment benefit and
      minimise harm. However, a lack of high quality evidence inhibits widespread
      implementation. This manuscript describes the rationale and design of a pragmatic
      cluster-randomised, crossover trial to fulfil this need for evidence. AIM: To
      study the effects of hospital-initiated comprehensive medication reviews,
      including active follow-up, on elderly patients' healthcare utilisation compared
      to 1) usual care and 2) solely hospital based reviews. DESIGN: Multicentre, three
      treatment, replicated, cluster-randomised, crossover trial. SETTING: 8 wards with
      a multidisciplinary team within 4 hospitals in 3 Swedish counties. PARTICIPANTS:
      Patients aged 65years or older, admitted to one of the study wards. EXCLUSION
      CRITERIA: Palliative stage; residing in other than the hospital's county;
      medication review within the last 30days; one-day admission. INTERVENTIONS: 1,
      comprehensive medication review during hospital stay; 2, same as 1 with the
      addition of active follow-up into primary care; 3, usual care. PRIMARY OUTCOME
      MEASURE: Incidence of unplanned hospital visits during a 12-month follow-up
      period. DATA COLLECTION AND ANALYSES: Extraction and collection from the
      counties' medical record system into a GCP compliant electronic data capture
      system. Intention-to-treat-analyses using hierarchical models. RELEVANCE: This
      study has a high potential to show a reduction in elderly patients' morbidity,
      contributing to more sustainable healthcare in the long run.

PMID- 28739540
TI  - The women in steady exercise research (WISER) survivor trial: The innovative
      transdisciplinary design of a randomized controlled trial of exercise and weight
      loss interventions among breast cancer survivors with lymphedema.
AB  - INTRODUCTION: Breast cancer survivors face dual challenges: long term sequelae of
      treatment, and risk of recurrent disease. Obesity and a sedentary lifestyle
      complicate both challenges. The WISER Survivor trial assessed the effects of
      exercise and/or weight-loss on lymphedema, biomarkers of breast cancer
      recurrence, and quality of life. We report on the innovative transdisciplinary
      design of this trial and report attrition rates. METHODS: This one year trial
      randomized breast cancer survivors who had a BMI of >=25kg/m2, were sedentary and
      had breast-cancer-related-lymphedema to 1) exercise (weight training and aerobic
      exercise) 2) weight-loss 3) exercise and weight-loss 4) or control group.
      Innovative aspects included: adaptation of a community-based weight training
      program to a largely home-based program; use of a commercial meal replacement
      system as part of the lifestyle modification weight-loss program; inclusion of
      measures of cost-effectiveness to enable economic evaluations; and alignment with
      a parallel mouse model for breast cancer recurrence to enable transdisciplinary
      research. In this model, mice bearing dormant residual tumor cells, which
      spontaneously relapse, were placed on a high-fat diet. Overweight animals were
      randomly assigned to exercise, calorie restriction, both, or control group and
      followed for cancer recurrence. The animal model will guide mechanistic
      biomarkers to be tested in the human trial. RESULTS & DISCUSSION: 351
      participants were randomized; 13 experienced breast cancer recurrence during the
      trial. Of the 338 participants without recurrence, 83% completed the trial. The
      WISER Survivor trial will show the effects of exercise and weight-loss on
      lymphedema outcomes, biomarkers of recurrence and quality of life. NCT
      ClinicalTrials.gov registration #: NCT01515124.

PMID- 28739541
TI  - Testing the comparative effects of physical activity advice by humans vs.
      computers in underserved populations: The COMPASS trial design, methods, and
      baseline characteristics.
AB  - : While physical inactivity is a key risk factor for a range of chronic diseases
      and conditions associated with aging, a significant proportion of midlife and
      older adults remain insufficiently active. This is particularly true for ethnic
      minority populations such as Latino adults for whom few culturally adapted
      programs have been developed and tested. The major objective of this 12-month
      cluster-randomized controlled trial is to test the comparative effectiveness of
      two linguistically and culturally adapted, community-based physical activity
      interventions with the potential for broad reach and translation. Ten local
      community centers serving a sizable number of Latino residents were randomized to
      receive one of two physical activity interventions. The Virtual Advisor program
      employs a computer-based embodied conversational agent named "Carmen" to deliver
      interactive, individually tailored physical activity advice and support. A
      similar intervention program is delivered by trained Peer Advisors. The target
      population consists of generally healthy, insufficiently active Latino adults
      ages 50years and older living within proximity to a designated community center.
      The major outcomes are changes in walking and other forms of physical activity
      measured via self-report and accelerometry. Secondary outcomes include physical
      function and well-being variables. In addition to these outcome analyses,
      comparative cost analysis of the two programs, potential mediators of
      intervention success, and baseline moderators of intervention effects will be
      explored to better determine which subgroups do best with which type of
      intervention. Here we present the study design and methods, including recruitment
      strategies and yield as well as study baseline characteristics. TRIAL
      REGISTRATION: clinicaltrial.gov Identifier=NCT02111213.

PMID- 28739542
TI  - A cluster randomized control trial to assess the impact of active learning on
      child activity, attention control, and academic outcomes: The Texas I-CAN trial.
AB  - BACKGROUND: Active learning is designed to pair physical activity with the
      teaching of academic content. This has been shown to be a successful strategy to
      increase physical activity and improve academic performance. The existing designs
      have confounded academic lessons with physical activity. As a result, it is
      impossible to determine if the subsequent improvement in academic performance is
      due to: (1) physical activity, (2) the academic content of the active learning,
      or (3) the combination of academic material taught through physical activity.
      METHODS/DESIGN: The Texas I-CAN project is a 3-arm, cluster randomized control
      trial in which 28 elementary schools were assigned to either control, math
      intervention, or spelling intervention. As a result, each intervention condition
      serves as an unrelated content control for the other arm of the trial, allowing
      the impact of physical activity to be separated from the content. That is,
      schools that perform only active math lessons provide a content control for the
      spelling schools on spelling outcomes. This also calculated direct observations
      of attention and behavior control following periods of active learning.
      DISCUSSION: This design is unique in its ability to separate the impact of
      physical activity, in general, from the combination of physical activity and
      specific academic content. This, in combination with the ability to examine both
      proximal and distal outcomes along with measures of time on task will do much to
      guide the design of future, school-based interventions.

PMID- 28739543
TI  - Dragonfly wing nodus: A one-way hinge contributing to the asymmetric wing
      deformation.
AB  - : Dragonfly wings are highly specialized locomotor systems, which are formed by a
      combination of several structural components. The wing components, also known as
      structural elements, are responsible for the various aspects of the wing
      functionality. Considering the complex interactions between the wing components,
      modelling of the wings as a whole is only possible with inevitable huge
      oversimplifications. In order to overcome this difficulty, we have recently
      proposed a new approach to model individual components of complex wings
      comparatively. Here, we use this approach to study nodus, a structural element of
      dragonfly wings which has been less studied to date. Using a combination of
      several imaging techniques including scanning electron microscopy (SEM), wide
      field fluorescence microscopy (WFM), confocal laser scanning microscopy (CLSM)
      and micro-computed tomography (micro-CT) scanning, we aim to characterize the
      spatial morphology and material composition of fore- and hindwing nodi of the
      dragonfly Brachythemis contaminata. The microscopy results show the presence of
      resilin in the nodi, which is expected to help the deformability of the wings.
      The computational results based on three-dimensional (3D) structural data suggest
      that the specific geometry of the nodus restrains its displacements when
      subjected to pressure on the ventral side. This effect, resulting from an
      interlocking mechanism, is expected to contribute to the dorso-ventral asymmetry
      of wing deformation and to provide a higher resistance to aerodynamic forces
      during the downstroke. Our results provide an important step towards better
      understanding of the structure-property-function relationship in dragonfly wings.
      STATEMENT OF SIGNIFICANCE: In this study, we investigate the wing nodus, a
      specialized wing component in dragonflies. Using a combination of modern imaging
      techniques, we demonstrate the presence of resilin in the nodus, which is
      expected to facilitate the wing deformability in flight. The specific geometry of
      the nodus, however, seems to restrain its displacements when subjected to
      pressure on the ventral side. This effect, resulting from an interlocking
      mechanism, is suggested to contribute to dorso-ventral asymmetry of wing
      deformations and to provide a higher resistance to aerodynamic forces during the
      downstroke. Our results provide an important step towards better understanding of
      the structure-property-function relationship in dragonfly wings and might help to
      design more efficient wings for biomimetic micro-air vehicles.

PMID- 28739544
TI  - In vitro degradation of calcium phosphates: Effect of multiscale porosity,
      textural properties and composition.
AB  - : The capacity of calcium phosphates to be replaced by bone is tightly linked to
      their resorbability. However, the relative importance of some textural parameters
      on their degradation behavior is still unclear. The present study aims to
      quantify the effect of composition, specific surface area (SSA), and porosity at
      various length scales (nano-, micro- and macroporosity) on the in vitro
      degradation of different calcium phosphates. Degradation studies were performed
      in an acidic medium to mimic the osteoclastic environment. Small degradations
      were found in samples with interconnected nano- and micropores with sizes below
      3um although they were highly porous (35-65%), with maximum weight loss of 8wt%.
      Biomimetic calcium deficient hydroxyapatite, with high SSA and low crystallinity,
      presented the highest degradation rates exceeding even the more soluble beta-TCP.
      A dependence of degradation on SSA was indisputable when porosity and pore sizes
      were increased. The introduction of additional macroporosity with pore
      interconnections above 20um significantly impacted degradation, more markedly in
      the substrates with high SSA (>15m2/g), whereas in sintered substrates with low
      SSA (<1m2/g) it resulted just in a linear increase of degradation. Up to 30 % of
      degradation was registered in biomimetic substrates, compared to 15 % in beta-TCP
      or 8 % in sintered hydroxyapatite. The incorporation of carbonate in calcium
      deficient hydroxyapatite did not increase its degradation rate. Overall, the
      study highlights the importance of textural properties, which can modulate or
      even outweigh the effect of other features such as the solubility of the
      compounds. STATEMENT OF SIGNIFICANCE: The physicochemical features of calcium
      phosphates are crucial to tune biological events like resorption during bone
      remodeling. Understanding in vitro resorption can help to predict the in vivo
      behavior. Besides chemical composition, other parameters such as porosity and
      specific surface area have a strong influence on resorption. The complexity of
      isolating the contribution of each parameter lies in the close interrelation
      between them. In this work, a multiscale study was proposed to discern the extent
      to which each parameter influences degradation in a variety of calcium
      phosphates, using an acidic medium to resemble the osteoclastic environment. The
      results emphasize the importance of textural properties, which can modulate or
      even outweigh the effect of the intrinsic solubility of the compounds.

PMID- 28739545
TI  - An optimized non-destructive protocol for testing mechanical properties in
      decellularized rabbit trachea.
AB  - : Successful tissue-engineered tracheal transplantation relies on the use of non
      immunogenic constructs, which can vascularize rapidly, support epithelial growth,
      and retain mechanical properties to that of native trachea. Current strategies to
      assess mechanical properties fail to evaluate the trachea to its physiological
      limits, and lead to irreversible destruction of the construct. Our aim was to
      develop and evaluate a novel non-destructive method for biomechanical testing of
      tracheae in a rabbit decellularization model. To validate the performance of this
      method, we simultaneously analyzed quantitative and qualitative graft changes in
      response to decellularization, as well as in vivo biocompatibility of implanted
      scaffolds. Rabbit tracheae underwent two, four and eight cycles of detergent
      enzymatic decellularization. Biomechanical properties were analyzed by
      calculating luminal volume of progressively inflated and deflated tracheae with
      microCT. DNA, glycosaminoglycan and collagen contents were compared to native
      trachea. Scaffolds were prelaminated in vivo. Native, two- and four-cycle
      tracheae showed equal mechanical properties. Collapsibility of eight-cycle
      tracheae was significantly increased from -40cm H2O (-3.9kPa). Implantation of
      two- and four-cycle decellularized scaffolds resulted in favorable flap-ingrowth;
      eight-cycle tracheae showed inadequate integration. We showed a more limited
      detergent-enzymatic decellularization successfully removing non-cartilaginous
      immunogenic matter without compromising extracellular matrix content or
      mechanical stability. With progressive cycles of decellularization, important
      loss of functional integrity was detected upon mechanical testing and in vivo
      implantation. This instability was not revealed by conventional quantitative nor
      qualitative architectural analyses. These experiments suggest that non
      destructive, functional evaluation, e.g. by microCT, may serve as an important
      tool for mechanical screening of scaffolds before clinical implementation.
      STATEMENT OF SIGNIFICANCE: Decellularization is a front-running strategy to
      generate scaffolds for tracheal tissue-engineering. Preservation of biomechanical
      properties of the trachea during this process is paramount to successful clinical
      transplantation. In this paper, we evaluated a novel method for biomechanical
      testing of decellularized trachea. We detected important loss of functional
      integrity with progressive cycles of decellularization. This instability was not
      revealed by our quantitative nor qualitative analyses. These experiments suggest
      that the technique might serve as a performant, non-destructive tool for
      mechanical screening of scaffolds before clinical implementation.

PMID- 28739546
TI  - In-situ tissue regeneration through SDF-1alpha driven cell recruitment and
      stiffness-mediated bone regeneration in a critical-sized segmental femoral
      defect.
AB  - : In-situ tissue regeneration aims to utilize the body's endogenous healing
      capacity through the recruitment of host stem or progenitor cells to an injury
      site. Stromal cell-derived factor-1alpha (SDF-1alpha) is widely discussed as a
      potent chemoattractant. Here we use a cell-free biomaterial-based approach to (i)
      deliver SDF-1alpha for the recruitment of endogenous bone marrow-derived stromal
      cells (BMSC) into a critical-sized segmental femoral defect in rats and to (ii)
      induce hydrogel stiffness-mediated osteogenic differentiation in-vivo. Ionically
      crosslinked alginate hydrogels with a stiffness optimized for osteogenic
      differentiation were used. Fast-degrading porogens were incorporated to impart a
      macroporous architecture that facilitates host cell invasion. Endogenous cell
      recruitment to the defect site was successfully triggered through the controlled
      release of SDF-1alpha. A trend for increased bone volume fraction (BV/TV) and a
      significantly higher bone mineral density (BMD) were observed for gels loaded
      with SDF-1alpha, compared to empty gels at two weeks. A trend was also observed,
      albeit not statistically significant, towards matrix stiffness influencing BV/TV
      and BMD at two weeks. However, over a six week time-frame, these effects were
      insufficient for bone bridging of a segmental femoral defect. While mechanical
      cues combined with ex-vivo cell encapsulation have been shown to have an effect
      in the regeneration of less demanding in-vivo models, such as cranial defects of
      nude rats, they are not sufficient for a SDF-1alpha mediated in-situ regeneration
      approach in segmental femoral defects of immunocompetent rats, suggesting that
      additional osteogenic cues may also be required. STATEMENT OF SIGNIFICANCE:
      Stromal cell-derived factor-1alpha (SDF-1alpha) is a chemoattractant used to
      recruit host cells for tissue regeneration. The concept that matrix stiffness can
      direct mesenchymal stromal cell (MSC) differentiation into various lineages was
      described a decade ago using in-vitro experiments. Recently, alginate hydrogels
      with an optimized stiffness and ex-vivo encapsulated MSCs were shown to have an
      effect in the regeneration of skull defects of nude rats. Here, we apply this
      material system, loaded with SDF-1alpha and without encapsulated MSCs, to (i)
      recruit endogenous cells and (ii) induce stiffness-mediated osteogenic
      differentiation in-vivo, using as model system a load-bearing femoral defect in
      immunocompetent rats. While a cell-free approach is of great interest from a
      translational perspective, the current limitations are described.

PMID- 28739547
TI  - Mogamulizumab-induced toxicoderma-like eruptions and autoimmune hepatitis
      successfully treated with azathioprine in adult T-cell leukaemia/lymphoma.

PMID- 28739548
TI  - The role of miR-210, E2F3 and ephrin A3 in angiosarcoma cell proliferation.
AB  - BACKGROUND: Although angiosarcoma exhibits aggressive progression and is
      associated with unfavourable prognosis, its pathogenesis is poorly understood.
      OBJECTIVES: In the present study, we investigated the possibility that microRNAs
      play a role in the pathogenesis of angiosarcoma. MATERIALS & METHODS: microRNA
      expression was evaluated by array analysis and real-time PCR, and protein
      expression was determined by immunohistochemistry and immunoblotting. RESULTS:
      miR-210 expression was decreased in angiosarcoma cells both in vivo and in vitro.
      E2F3 and ephrin A3 are putative targets of miR-210, and their protein expression
      was up-regulated in the tumour cells. Knockdown of E2F3 or ephrin A3 resulted in
      a significant decrease in the number of angiosarcoma cells. CONCLUSION: Further
      investigations into the regulatory mechanisms of oncogenesis associated with miR
      210/E2F3/ephrin A3 signalling may lead to a new therapeutic approach against
      angiosarcoma.

PMID- 28739549
TI  - Mutations in the ABCG8 gene are associated with sitosterolaemia in the homozygous
      form and xanthelasmas in the heterozygous form.
AB  - : Sitosterol is the most abundant plant sterol found in our diet. Sitosterolemia
      (OMIM 210250), also known as phytosterolaemia, is a rare autosomal recessive
      disease caused by the inability to efficiently excrete plant sterol, and is
      characterized by cutaneous xanthomas and accelerated atherosclerosis.
      Sitosterolaemia is caused by homozygous or compound heterozygous mutations in
      either ABCG5 or ABCG8 (both on chromosome 2p21), which encode the sterol efflux
      transporter ABCG5 (sterolin-1) and ABCG8 (sterolin-2), respectively. To
      investigate a Tunisian family with several members who manifested with
      generalized cutaneous xanthomas, whereas others had only isolated xanthelasmas.
      Genetic analysis was performed based on exome sequencing of DNA obtained from
      five affected individuals and one unaffected individual from a Tunisian family.
      RESULTS: A novel mutation in the ABCG8 gene, designated c.965-1G>C, was
      identified by exome sequencing in the members of this family. The homozygous form
      was associated with generalized cutaneous xanthomatosis while the heterozygous
      form was linked to isolated xanthelasmas. Our results indicate a gene dosage
      effect of ABCG8 and suggest that individuals at risk should be followed closely.

PMID- 28739550
TI  - Nivolumab-induced vitiligo successfully treated with narrowband UVB phototherapy.

PMID- 28739551
TI  - A Patient with Proopiomelanocortin Deficiency: An Increasingly Important
      Diagnosis to Make.
AB  - Proopiomelanocortin (POMC) deficiency is a rare monogenic disorder with early
      onset obesity. Investigation of this entity have increased our insight into the
      important role of the leptin-melanocortin pathway in energy balance. Here, we
      present a patient with POMC deficiency due to a homozygous c.206delC mutation in
      the POMC gene. We discuss the pathogenesis of this condition with emphasis on the
      crosstalk between hypothalamic and peripheral signals in the development of
      obesity and the POMC-melanocortin 4 receptors system as a target for therapeutic
      intervention.

PMID- 28739552
TI  - An Assessment of Retinal Nerve Fiber Layer Thickness in Non-Diabetic Obese
      Children and Adolescents.
AB  - OBJECTIVE: Obesity affects almost all systems in the body. This includes the
      retinal nerve fibers which may be damaged due to a chronic inflammatory process.
      To determine changes in retinal nerve fiber layer (RNFL) thickness in non
      diabetic children and adolescents using optical coherence tomography (OCT) and to
      evaluate the relationship between this change, metabolic risk factors and
      pubertal stage. METHODS: Thirty-eight obese and 40 healthy children and
      adolescents aged 10-18 years were included in the study. RNFL measurements from
      the optic disk and all surrounding quadrants were obtained using OCT from both
      eyes of the individuals in the study groups. Correlations between RNFL thickness
      and age, auxological measurements, pubertal stage, systolic and diastolic blood
      pressure, homeostasis model assessment-insulin resistance (HOMA-IR) index and
      lipid values were investigated. RESULTS: A general decrease was observed in RNFL
      thickness in obese subjects compared to the controls, the decrease being highest
      in the inferior quadrant, although these differences were not statistically
      significant (p>0.05). RNFL thickness was negatively correlated with body mass
      index (BMI) standard deviation score (SDS) in both groups (control group r=
      0.345, p=0.029; obese group r=-0.355, p=0.022). Significant negative correlations
      were determined between diastolic blood pressure, HOMA-IR, low density
      lipoprotein cholesterol level and RNFL thickness (r=-0.366, p=0.024; r=-0.394,
      p=0.016; and r=-0.374, p=0.022, respectively) in the obese group, while there was
      no association between these parameters and RNFL thickness in the control group.
      CONCLUSION: In this cross-sectional study, no statistically significant
      difference in RNFL thicknesses between the obese and control groups was
      determined. However, RNFL thickness was found to decrease in both healthy and
      obese children as BMI-SDS values increased. Further prospective studies may be of
      benefit to determine whether the decrease in RNFL values might become more
      pronounced on long-term follow-up.

PMID- 28739553
TI  - Acute Effects of Blood Transfusion on Insulin Sensitivity and Pancreatic beta
      Cell Function in Children with beta-Thalassemia/Hemoglobin E Disease.
AB  - OBJECTIVE: To assess the acute effects of blood transfusion on insulin
      sensitivity and pancreatic beta-cell function in thalassemia patients. METHODS:
      Fifty children and adolescents with beta-thalassemia/HbE disease were enrolled in
      a prospective cohort study. Hemoglobin, serum ferritin and oral glucose tolerance
      test (OGTT) were performed prior to, and one week after blood transfusion.
      Insulin sensitivity indices [homeostatic model assessment (HOMA) of insulin
      resistance (HOMA-IR), whole body insulin sensitivity index (WBISI)] and beta-cell
      function indices [HOMA of beta-cell function (HOMA-beta), insulinogenic index
      (IGI), and disposition index (DI)] were calculated from glucose and insulin
      levels obtained during the OGTT. RESULTS: Following blood transfusion, hemoglobin
      and serum ferritin increased significantly; 8.5 to 10.1 g/dL (p<0.001) and 1764
      to 2160 ng/mL (p<0.001), respectively. beta-Cell function indices also increased
      significantly [median HOMA-beta: 74.3 vs. 82.7 (p=0.033); median IGI: 59.6 vs.
      79.3 (p=0.003); median DI: 658 vs. 794 (p=0.01)]. However, the insulin
      sensitivity index (WBISI) tended to decrease and the insulin resistance index
      (HOMA-IR) tended to increase although this did not reach significance.
      Multivariate analysis showed that pre-transfusion serum ferritin was the major
      factor negatively associated with WBISI and positively associated with HOMA-IR,
      but pre-transfusion hemoglobin had no significant association with insulin
      sensitivity indices post-transfusion. CONCLUSION: This study demonstrated that
      acute increases in serum ferritin and hemoglobin following blood transfusion in
      patients with thalassemia might contribute to an increase in insulin secretion
      and to a trend towards increased insulin resistance.

PMID- 28739554
TI  - 46,XY Disorder of Sex Development due to 17-Beta Hydroxysteroid Dehydrogenase
      Type 3 Deficiency in an Infant of Greek Origin.
AB  - 17-beta hydroxysteroid dehydrogenase type 3 (17betaHSD-3) enzyme catalyzes the
      conversion of androstenedione (Delta4) to testosterone (T) in the testes of the
      developing fetus, thus playing a crucial role in the differentiation of the
      gonads and in establishing the male sex phenotype. Any mutation in the encoding
      gene (HSD17B3) can lead to varying degrees of undervirilization of the affected
      male, ranging from completely undervirilized external female genitalia to
      predominantly male with micropenis and hypospadias. We present here an infant who
      was referred to our clinic because of ambiguous genitalia at birth. Gonads were
      palpable in the inguinal canal bilaterally and no Mullerian structures were
      identified on pelvic ultrasound. Because of a low T/Delta4 ratio after a human
      chorionic gonadotropin stimulation test, a tentative diagnosis of 17betaHSD-3
      deficiency was made which was confirmed after genetic analysis of the HSD17B3
      gene of the patient. The molecular analysis identified compound heterozygosity of
      two previously described mutations and could offer some further validation for
      the idea of a founder effect for 655-1;G->A mutation in the Greek population.

PMID- 28739555
TI  - Serum Nesfatin-1 Levels in Girls with Idiopathic Central Precocious Puberty.
AB  - OBJECTIVE: Nesfatin-1, an anorexigenic neuropeptide, is expressed mainly in the
      central nervous system and in some peripheral tissues. The role of nesfatin-1 in
      energy balance has been investigated. Despite the suggestion of a role for
      nesfatin-1 in reproductive function, data are limited on the role of nesfatin-1
      in human puberty. METHODS: The aim of this study was to investigate the
      following: i) the role of nesfatin-1 in puberty, and ii) relationship between
      nesfatin-1 and anthropometric measurements and gonadotropin levels in girls with
      idiopathic central precocious puberty (CPP). Twenty-four girls with CPP (7.68+/
      1.02 years) and 20 female, prepubertal, healthy controls (7.48+/-0.88 years) were
      enrolled in the study. All patients with CPP were treated by the intramuscular
      administration of leuprolide acetate at a daily dose of 3.75 mg for 28 days.
      Nesfatin-1 was measured before and during treatment. RESULTS: There was no
      difference in serum nesfatin-1 levels in girls with CPP and healthy controls
      [5.67 (2.5-20.6) mmol/L and 5.75 (2.51-9.64) mmol/L], respectively. There was a
      negative correlation between nesfatin-1 levels and body weight and body mass
      index-standard deviation score (p=0.01, r=-0.83; p=0.025, r=-0.81, respectively).
      No correlation was found between nesfatin-1 and gonadotropin, estradiol levels,
      uterine length or endometrial thickness. CONCLUSION: The results of this study
      suggest that there are no differences between girls with CPP and healthy,
      prepubertal girls regarding nesfatin-1 levels.

PMID- 28739556
TI  - Plasma Amino-Terminal Propeptide of C-Type Natriuretic Peptide Concentration in
      Normal-Weight and Obese Children.
AB  - OBJECTIVE: In studies on the relationship between amino-terminal propeptide of C
      type natriuretic peptide (NT-proCNP) concentration and height velocity in
      children, CNP has been implicated as an emerging new growth marker during
      childhood. It has been reported that besides its well-studied role in growth,
      plasma CNP levels are reduced in overweight and/or obese adolescents, suggesting
      CNP as a potential biomarker in childhood obesity. The primary goal of this study
      was to test this hypothesis in a Turkish population. METHODS: Consent was taken
      from 317 children [ages 0-18 (158 girls, 159 boys)] and their parents. All
      subjects were physically examined; anthropometric measurements were obtained.
      Body mass index was calculated. During routine blood work, 1 mL extra blood was
      taken. Plasma NT-proCNP concentration was measured by enzyme-linked immunosorbent
      assay. RESULTS: Results confirmed the previously described relationship between
      plasma NT-proCNP concentration and growth velocity. Plasma NT-proCNP
      concentration showed a negative correlation with age, weight, and height in
      children. Gender was not a factor that alters the age-dependent plasma NT-proCNP
      concentration until puberty. CONCLUSION: Unlike previous reports, plasma NT
      proCNP concentration of overweight/obese children was not significantly lower
      than that of children with normal weight in age groups analyzed in a Turkish
      population. Thus, it is too early to conclude that CNP is a potential biomarker
      in childhood obesity. Further studies are necessary to address this question.

PMID- 28739557
TI  - Facebook Recruitment of Vaccine-Hesitant Canadian Parents: Cross-Sectional Study.
AB  - BACKGROUND: There is concern over the increase in the number of "vaccine
      hesitant" parents, which contributes to under-vaccinated populations and reduced
      herd immunity. Traditional studies investigating parental immunization beliefs
      and practices have relied on random digit dialing (RDD); however, this method
      presents increasing limitations. Facebook is the most used social media platform
      in Canada and presents an opportunity to recruit vaccine-hesitant parents in a
      novel manner. OBJECTIVE: The study aimed to explore the use of Facebook as a tool
      to reach vaccine-hesitant parents, as compared with RDD methods. METHODS: We
      recruited Canadian parents over 4 weeks in 2013-14 via targeted Facebook
      advertisements linked to a Web-based survey. We compared methodological
      parameters, key parental demographics, and three vaccine hesitancy indicators to
      an RDD sample of Canadian parents. Two raters categorized respondent reasons for
      difficulties in deciding to vaccinate, according to the model of determinants of
      vaccine hesitancy developed by the World Health Organization's Strategic Advisory
      Group of Experts on Immunization. RESULTS: The Facebook campaign received a total
      of 4792 clicks from unique users, of whom 1696 started the Web-based survey. The
      total response rate of fully completed unique Web-based surveys was 22.89%
      (1097/4792) and the survey completion rate was 64.68% (1097/1696). The total cost
      including incentives was reasonable (Can $4861.19). The Web-based sample yielded
      younger parents, with 85.69% (940/1097) under the age of 40 years as compared
      with 23.38% (408/1745) in the RDD sample; 91.43% (1003/1097) of the Facebook
      respondents were female as compared with 59.26% (1034/1745) in the RDD sample.
      Facebook respondents had a lower median age of their youngest child (1 year vs 8
      years for RDD). When compared with the RDD sample, the Web-based sample yielded a
      significantly higher proportion of respondents reporting vaccines as moderately
      safe to not safe (26.62% [292/1097] vs 18.57% [324/1745]), partially or not at
      all up-to-date vaccination status of youngest child (22.06% [242/1097] vs 9.57%
      [167/1745]), and difficulty in making the decision to vaccinate their youngest
      child (21.06% [231/1097] vs 10.09% [176/1745]). Out of the Web-based respondents
      who reported reasons for the difficulties in deciding to vaccinate, 37.2%
      (83/223) reported lack of knowledge or trust due to conflicting information and
      23.8% (53/223) reported the perception of the risk of the adverse effects of
      vaccines being higher than the risk of disease acquisition. CONCLUSIONS: We
      successfully recruited a large sample of our target population at low cost and
      achieved a high survey completion rate using Facebook. When compared with the RDD
      sampling strategy, we reached more vaccine-hesitant parents and younger parents
      with younger children-a population more likely to be making decisions on
      childhood immunizations. Facebook is a promising economical modality for reaching
      vaccine-hesitant parents for studies on the determinants of vaccine uptake.

PMID- 28739558
TI  - Design of Mobile Health Tools to Promote Goal Achievement in Self-Management
      Tasks.
AB  - BACKGROUND: Goal-setting within rehabilitation is a common practice ultimately
      geared toward helping patients make functional progress. OBJECTIVE: The purposes
      of this study were to (1) qualitatively analyze data from a wellness program for
      patients with spina bifida (SB) and spinal cord injury (SCI) in order to generate
      software requirements for a goal-setting module to support their complex goal
      setting routines, (2) design a prototype of a goal-setting module within an
      existing mobile health (mHealth) system, and (3) identify what educational
      content might be necessary to integrate into the system. METHODS: A total of 750
      goals were analyzed from patients with SB and SCI enrolled in a wellness program.
      These goals were qualitatively analyzed in order to operationalize a set of
      software requirements for an mHealth goal-setting module and identify important
      educational content. RESULTS: Those of male sex (P=.02) and with SCI diagnosis
      (P<.001) were more likely to achieve goals than females or those with SB.
      Temporality (P<.001) and type (P<.001) of goal were associated with likelihood
      that the goal would be achieved. Nearly all (210/213; 98.6%) of the fact-finding
      goals were achieved. There was no significant difference in achievement based on
      goal theme. Checklists, data tracking, and fact-finding tools were identified as
      three functionalities that could support goal-setting and achievement in an
      mHealth system. Based on the qualitative analysis, a list of software
      requirements for a goal-setting module was generated, and a prototype was
      developed. Targets for educational content were also generated. CONCLUSIONS:
      Innovative mHealth tools can be developed to support commonly set goals by
      individuals with disabilities.

PMID- 28739559
TI  - Nurse-Moderated Internet-Based Support for New Mothers: Non-Inferiority,
      Randomized Controlled Trial.
AB  - BACKGROUND: Internet-based interventions moderated by community nurses have the
      potential to improve support offered to new mothers, many of whom now make
      extensive use of the Internet to obtain information about infant care. However,
      evidence from population-based randomized controlled trials is lacking.
      OBJECTIVE: The aim of this study was to test the non-inferiority of outcomes for
      mothers and infants who received a clinic-based postnatal health check plus nurse
      moderated, Internet-based group support when infants were aged 1-7 months as
      compared with outcomes for those who received standard care consisting of
      postnatal home-based support provided by a community nurse. METHODS: The design
      of the study was a pragmatic, preference, non-inferiority randomized control
      trial. Participants were recruited from mothers contacted for their postnatal
      health check, which is offered to all mothers in South Australia. Mothers were
      assigned either (1) on the basis of their preference to clinic+Internet or home
      based support groups (n=328), or (2) randomly assigned to clinic+Internet or home
      based groups if they declared no strong preference (n=491). The overall response
      rate was 44.8% (819/1827). The primary outcome was parenting self-competence, as
      measured by the Parenting Stress Index (PSI) Competence subscale, and the
      Karitane Parenting Confidence Scale scores. Secondary outcome measures included
      PSI Isolation, Interpersonal Support Evaluation List-Short Form, Maternal Support
      Scale, Ages and Stages Questionnaire-Social-Emotional and MacArthur Communicative
      Development Inventory (MCDI) scores. Assessments were completed offline via self
      assessment questionnaires at enrolment (mean child age=4.1 weeks, SD 1.3) and
      again when infants were aged 9, 15, and 21 months. RESULTS: Generalized
      estimating equations adjusting for post-randomization baseline imbalances showed
      that differences in outcomes between mothers in the clinic+Internet and home
      based support groups did not exceed the pre-specified margin of inferiority (0.25
      of a SD) on any outcome measure at any follow-up assessment, with the exception
      of MCDI scores assessing children's language development at 21 months for
      randomized mothers, and PSI Isolation scores at 9 months for preference mothers.
      CONCLUSION: Maternal and child outcomes from a clinic-based postnatal health
      check plus nurse-moderated Internet-based support were not inferior to those
      achieved by a universal home-based postnatal support program. Postnatal maternal
      and infant support using the Internet is a promising alternative to home-based
      universal support programs. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry Number (ANZCTR): ACTRN12613000204741;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363712&isReview=
      rue (Archived by WebCite at http://www.webcitation.org/6rZeCJ3k1).

PMID- 28739560
TI  - Ontology-Based Approach to Social Data Sentiment Analysis: Detection of
      Adolescent Depression Signals.
AB  - BACKGROUND: Social networking services (SNSs) contain abundant information about
      the feelings, thoughts, interests, and patterns of behavior of adolescents that
      can be obtained by analyzing SNS postings. An ontology that expresses the shared
      concepts and their relationships in a specific field could be used as a semantic
      framework for social media data analytics. OBJECTIVE: The aim of this study was
      to refine an adolescent depression ontology and terminology as a framework for
      analyzing social media data and to evaluate description logics between classes
      and the applicability of this ontology to sentiment analysis. METHODS: The domain
      and scope of the ontology were defined using competency questions. The concepts
      constituting the ontology and terminology were collected from clinical practice
      guidelines, the literature, and social media postings on adolescent depression.
      Class concepts, their hierarchy, and the relationships among class concepts were
      defined. An internal structure of the ontology was designed using the entity
      attribute-value (EAV) triplet data model, and superclasses of the ontology were
      aligned with the upper ontology. Description logics between classes were
      evaluated by mapping concepts extracted from the answers to frequently asked
      questions (FAQs) onto the ontology concepts derived from description logic
      queries. The applicability of the ontology was validated by examining the
      representability of 1358 sentiment phrases using the ontology EAV model and
      conducting sentiment analyses of social media data using ontology class concepts.
      RESULTS: We developed an adolescent depression ontology that comprised 443
      classes and 60 relationships among the classes; the terminology comprised 1682
      synonyms of the 443 classes. In the description logics test, no error in
      relationships between classes was found, and about 89% (55/62) of the concepts
      cited in the answers to FAQs mapped onto the ontology class. Regarding
      applicability, the EAV triplet models of the ontology class represented about
      91.4% of the sentiment phrases included in the sentiment dictionary. In the
      sentiment analyses, "academic stresses" and "suicide" contributed negatively to
      the sentiment of adolescent depression. CONCLUSIONS: The ontology and terminology
      developed in this study provide a semantic foundation for analyzing social media
      data on adolescent depression. To be useful in social media data analysis, the
      ontology, especially the terminology, needs to be updated constantly to reflect
      rapidly changing terms used by adolescents in social media postings. In addition,
      more attributes and value sets reflecting depression-related sentiments should be
      added to the ontology.

PMID- 28739561
TI  - Smartphone-Based Monitoring of Objective and Subjective Data in Affective
      Disorders: Where Are We and Where Are We Going? Systematic Review.
AB  - BACKGROUND: Electronic mental health interventions for mood disorders have
      increased rapidly over the past decade, most recently in the form of various
      systems and apps that are delivered via smartphones. OBJECTIVE: We aim to provide
      an overview of studies on smartphone-based systems that combine subjective
      ratings with objectively measured data for longitudinal monitoring of patients
      with affective disorders. Specifically, we aim to examine current knowledge on:
      (1) the feasibility of, and adherence to, such systems; (2) the association of
      monitored data with mood status; and (3) the effects of monitoring on clinical
      outcomes. METHODS: We systematically searched PubMed, Web of Science, PsycINFO,
      and the Cochrane Central Register of Controlled Trials for relevant articles
      published in the last ten years (2007-2017) by applying Boolean search operators
      with an iterative combination of search terms, which was conducted in February
      2017. Additional articles were identified via pearling, author correspondence,
      selected reference lists, and trial protocols. RESULTS: A total of 3463 unique
      records were identified. Twenty-nine studies met the inclusion criteria and were
      included in the review. The majority of articles represented feasibility studies
      (n=27); two articles reported results from one randomized controlled trial (RCT).
      In total, six different self-monitoring systems for affective disorders that used
      subjective mood ratings and objective measurements were included. These objective
      parameters included physiological data (heart rate variability), behavioral data
      (phone usage, physical activity, voice features), and context/environmental
      information (light exposure and location). The included articles contained
      results regarding feasibility of such systems in affective disorders, showed
      reasonable accuracy in predicting mood status and mood fluctuations based on the
      objectively monitored data, and reported observations about the impact of
      monitoring on clinical state and adherence of patients to the system usage.
      CONCLUSIONS: The included observational studies and RCT substantiate the value of
      smartphone-based approaches for gathering long-term objective data (aside from
      self-ratings to monitor clinical symptoms) to predict changes in clinical states,
      and to investigate causal inferences about state changes in patients with
      affective disorders. Although promising, a much larger evidence-base is necessary
      to fully assess the potential and the risks of these approaches. Methodological
      limitations of the available studies (eg, small sample sizes, variations in the
      number of observations or monitoring duration, lack of RCT, and heterogeneity of
      methods) restrict the interpretability of the results. However, a number of study
      protocols stated ambitions to expand and intensify research in this emerging and
      promising field.

PMID- 28739562
TI  - Polycystic ovary syndrome and the risk of obstructive sleep apnea: a meta
      analysis and review of the literature.
AB  - BACKGROUND AND OBJECTIVE: Polycystic ovary syndrome (PCOS) has been reported to
      be associated with the development of obstructive sleep apnea (OSA). The
      objective of this meta-analysis is to assess the relationship between PCOS and
      OSA. METHODS: A literature search was conducted to identify studies linking PCOS
      with the risk of OSA. Studies in which the presence of OSA was confirmed with
      overnight polysomnography were included. Random effects models were used to
      calculate pooled relative risks. RESULTS: Eight studies conducted in adults and
      five studies conducted in adolescents were identified. The pooled OSA prevalence
      was 0.22 (95% confidence interval (CI): 0.08-0.40) in PCOS patients. The pooled
      prevalence of OSA was higher in adults (0.32, 95% CI: 0.13-0.55) than adolescents
      (0.08, 95% CI: 0.00-0.30). Risk of OSA was significantly increased in adult
      patients with PCOS (odds ratio (OR) 9.74, 95% CI: 2.76-34.41). Risk of OSA was
      not significantly increased in adolescents (OR: 4.54, 95% CI:0.56-36.43).
      CONCLUSIONS: These findings demonstrate a significant association between PCOS
      and OSA in adult patients. Considering the increased risk for long-term
      cardiometabolic disorders associated with both PCOS and OSA, it is important to
      diagnose and treat OSA in patients with PCOS.

PMID- 28739563
TI  - Efficacy of new low-dose oral anticoagulants in recalcitrant livedoid
      vasculopathy.
AB  - Livedoid vasculopathy (LV) is a thrombotic skin disease characterised by
      recurrent painful ulcerations and irreversible scar formation on the lower legs,
      which is caused by occlusion of the cutaneous microcirculation. Edoxaban is one
      of new oral anticoagulants. It directly inhibits factor Xa in the coagulation
      pathway and prevents thrombus formation. A 17-year-old Japanese male presented
      with a 1-year history of recalcitrant cutaneous ulcers and livedo racemosa on his
      lower extremities. Initially, the ulcers were treated with antiplatelets
      therapies; however, he experienced recurrence of ulcerations during summer time.
      A histological examination revealed dermal vessel thrombosis consistent with
      occlusive vasculopathy. These findings were diagnostic for LV. The patient was
      treated with oral low-dose edoxaban (15 mg/day). The skin ulcers were epithelised
      and livedo racemosa disappeared within 8 weeks. We herein report the successful
      treatment of recalcitrant LV with low-dose edoxaban in a patient with no
      identifiable coagulopathy.

PMID- 28739564
TI  - Silent tracheobronchial chondritis in a patient with a delayed diagnosis of
      relapsing polychondritis.
AB  - Relapsing polychondritis is a very rare autoimmune disease characterised by a
      relapsing inflammation of hyaline, elastic and fibrous cartilaginous tissues. The
      incidence is estimated to be between 3.5 and 4.5 per million people per year.
      Clinical signs and symptoms can be very subtle, and if left undiagnosed for a
      prolonged period, airway involvement can cause fibrosis of the tracheobronchial
      wall, leading to a fixed tracheobronchial stenosis. Eventually, this can progress
      to life-threatening tracheobronchomalacia due to irreversible damage and loss of
      tissue integrity. We report an elderly man who presented with recurrent bilateral
      ear inflammation and intermittent polyarthritis who was diagnosed with relapsing
      polychondritis with asymptomatic involvement of his large airways.

PMID- 28739565
TI  - Unusual genitourinary tract activity.
AB  - A 23-year-old woman presented to the emergency department after manually
      inserting foreign bodies into the urinary bladder through her urethra. A plain
      abdominal film of the kidneys, ureters and bladder confirmed three radio-opaque
      densities in the urinary bladder. She was taken to the operating room where
      cystourethroscopy was performed. At cystoscopy 2 'corn-on-the-cob' skewers and 1
      battery were identified but were too large to be retrieved safely with a grasper
      through the protective sheath. The objects were grasped with a 'sponge-holding
      forceps' (placed alongside the cystoscope) and extracted one at a time. A
      psychiatric consultation was sought and the patient was diagnosed and treated for
      borderline personality disorder. Unusual genitourinary activity (UGUA) has been
      described for several centuries and is characterised by the deposition of foreign
      objects in the genitalia. 1 The most common incentive for UGUA is sexual
      stimulation, but psychiatric disorders and intoxication are also associated. 2
      Management involves retrieval of foreign bodies and evaluation of psychosocial
      factors.

PMID- 28739566
TI  - Loculated empyema due to tuberculosis in a child.
AB  - A 9-year-old girl from black ethnic origin presented with a history of fever,
      cough, loss of weight and right-sided chest wall pain for 2 weeks. Chest X-ray
      demonstrated an effusion, which was shown to be loculated on chest CT scan. She
      was not responding to medical treatment and at thoracotomy loculated pus was
      drained. Mycobacterium tuberculosis (TB) was cultured from the pus. TB is a rare
      cause of loculated empyema with an overlapping clinical and radiological picture
      with pyogenic infections.

PMID- 28739567
TI  - Case of a strangulated right paraduodenal fossa hernia in a malrotated gut.
AB  - We report an unusual case of a strangulated internal hernia resulting from a
      right paraduodenal fossa hernia (PDH) in the context of bowel malrotation. There
      are few documented cases of PDHs associated with a concomitant gut malrotation.
      Emergency laparotomy was performed based on clinical and radiological.
      Intraoperatively, the proximal jejunum was seen to enter a hernia sac formed by
      an aberrant duodenojejunal flexure located to the right of the aorta. This was
      presumed to be a strangulated internal hernia of the paraduodenal recess in a
      malrotated gut. The hernia neck was widened and the sac obliterated to allow
      reduction of the contents. On reduction and warming, the insulted small bowel
      appeared viable and returned to the abdominal cavity without resection.

PMID- 28739568
TI  - Posterior meningeal artery DMSO injection resulting in reproducible asystole
      prior to Onyx therapy of a dural arteriovenous fistula: a previously undescribed
      variant of the trigeminocardiac reflex or a new phenomenon?
AB  - We describe a case of reproducible asystole during endovascular treatment of a
      posterior fossa dural arteriovenous fistula. Catheterisation of the posterior
      meningeal artery, a branch of the vertebral artery in this patient, followed by
      dimethyl sulfoxide injection prior to Onyx administration resulted in two
      episodes of asystole.To the best of our knowledge, this is the first reported
      case of asystole occurring during endovascular intervention in the posterior
      meningeal artery. This may represent a previously undescribed variant of the
      trigemino-cardiac reflex (TGCR) caused by chemical stimulation of small areas of
      trigeminally innervated posterior fossa dura. Alternatively, this may represent a
      newly identified phenomenon with chemical stimulation of regions of posterior
      fossa dura innervated by branches of the vagus nerve leading to increased
      parasympathetic activity and resultant asystole.In either case, it is important
      to recognise the potential for such episodes in this vascular territory to allow
      case planning and management.

PMID- 28739569
TI  - Normal carboxyhaemoglobin level in carbon monoxide poisoning treated with
      hyperbaric oxygen therapy.
AB  - Throughout the world both intentional and inadvertent exposure to carbon monoxide
      (CO) remains an important public health issue. While CO poisoning can be lethal,
      the morbidity is predominantly due to nervous system injury. A previously healthy
      22-year-old woman was found unconscious at home by her sister. Her parents were
      found dead in the house with a recent history of a dysfunctional furnace. She was
      presumed to have CO poisoning despite an initial carboxyhaemoglobin level of
      2.5%. Patient had both clinical and radiological evidence of neurological damage.
      However, with multiple sessions of hyperbaric oxygen (HBO) therapy she recovered
      to a near normal functional status. There is no consensus that exists among
      treating physicians about the role of hyperbaric oxygen in management of
      neurological injury. The case described here has significant neurological damage
      related to CO exposure but improved after HBO therapy.

PMID- 28739570
TI  - Dengue fever presenting as cauda equina syndrome.

PMID- 28739571
TI  - Splice Variants of pH-Sensitive Chloride Channel Identify a Key Determinant of
      Ivermectin Sensitivity in the Larvae of the Silkworm Bombyx mori.
AB  - The pH-sensitive chloride channels (pHCls) are broadly expressed in insects, but
      little is known about their physiologic role, diversity, and sensitivity to
      insecticides acting on relevant chloride channels. Here we have sequenced 50
      transcripts of the pHCl-1 gene from the brain, third thoracic ganglion (T3G), and
      midgut of larvae of silkworm Bombyx mori It was found that >50 variants were
      expressed with distinct splicing in the T3G compared with the brain and midgut.
      Of the variants detected, variant 9, which was expressed most abundantly in the
      larvae, was reconstituted in Xenopus laevis oocytes to characterize its pH and
      ivermectin sensitivity. Variant 9 formed a functional pHCl with half-maximal
      activation at a pH of 7.87, and was activated by ivermectin irrespective of the
      extracellular pH. This was in contrast to variant 1, which was activated more
      profoundly at acidic rather than basic pH. To identify a key determinant for such
      differential ivermectin sensitivity, different amino acids in variants 1 and 9
      were swapped, and the effects of the mutations on ivermectin sensitivity were
      investigated. The V275S mutation of variant 1 enhanced ivermectin sensitivity,
      whereas the S275V mutation of variant 9 caused a reduction in sensitivity. In
      homology models of the Bombyx pHCls, Val275 of variant 1 interacted more strongly
      with Ala273 than Ser275 of variant 9 at the channel gate. This interaction is
      likely to prevent ivermectin-induced opening of the channel, accounting, at least
      partially, for the differential macrolide action on the two variants.

PMID- 28739573
TI  - Quality Assurance Audit of Technique Failure and 90-Day Mortality after Program
      Discharge in a Canadian Home Hemodialysis Program.
AB  - BACKGROUND AND OBJECTIVES: Little is known about patients exiting home
      hemodialysis. We sought to characterize the reasons, clinical characteristics,
      and pre-exit health care team interactions of patients on home hemodialysis who
      died or underwent modality conversion (negative disposition) compared with
      prevalent patients and those who were transplanted (positive disposition).
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted an audit of all
      consecutive patients incident to home hemodialysis from January of 2010 to
      December of 2014 as part of ongoing quality assurance. Records were reviewed for
      the 6 months before exit, and vital statistics were assessed up to 90 days
      postexit. RESULTS: Ninety-four patients completed training; 25 (27%) received a
      transplant, 11 (12%) died, and 23 (25%) were transferred to in-center
      hemodialysis. Compared with the positive disposition group, patients in the
      negative disposition group had a longer mean dialysis vintage (3.15 [SD=4.98]
      versus 1.06 [SD=1.16] years; P=0.003) and were performing conventional versus a
      more intensive hemodialysis prescription (23 of 34 versus 23 of 60; P<0.01). In
      the 6 months before exit, the negative disposition group had significantly more
      in-center respite dialysis sessions, had more and longer hospitalizations, and
      required more on-call care team support in terms of phone calls and drop-in
      visits (each P<0.05). The most common reason for modality conversion was medical
      instability in 15 of 23 (65%) followed by caregiver or care partner burnout in
      three of 23 (13%) each. The 90-day mortality among patients undergoing modality
      conversion was 26%. CONCLUSIONS: Over a 6-year period, approximately one third of
      patients exited the program due to death or modality conversion. Patients who die
      or transfer to another modality have significantly higher health care resource
      utilization (e.g., hospitalization, respite treatments, nursing time, etc.).

PMID- 28739574
TI  - Maintaining Patients on Home Hemodialysis: The Journey Matters as Does the
      Destination.

PMID- 28739572
TI  - Altenusin, a Nonsteroidal Microbial Metabolite, Attenuates Nonalcoholic Fatty
      Liver Disease by Activating the Farnesoid X Receptor.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease.
      The incidence of NAFLD has increased steadily due to its close association with
      the global epidemic of obesity and type 2 diabetes. However, there is no
      effective pharmacological therapy approved for NAFLD. Farnesoid X receptor (FXR),
      a member of the nuclear receptor subfamily, plays important roles in maintaining
      the homeostasis of bile acids, glucose, and lipids. FXR agonists have shown
      promise for the treatment of NAFLD. In this study, we report altenusin (2076A), a
      natural nonsteroidal fungal metabolite, as a novel selective agonist of FXR with
      an EC50 value of 3.2 +/- 0.2 MUM. Administration of 2076A protected mice from
      high-fat diet (HFD)-induced obesity by reducing the body weight and fat mass by
      22.9% and 50.0%, respectively. Administration of 2076A also decreased the blood
      glucose level from 178.3 +/- 12.4 mg/dl to 116.2 +/- 4.1 mg/dl and the serum
      insulin level from 1.4 +/- 0.6 ng/dl to 0.4 +/- 0.1 ng/dl. Moreover, 2076A
      treatment nearly reversed HFD-induced hepatic lipid droplet accumulation and
      macrovesicular steatosis. These metabolic effects were abolished in FXR knockout
      mice. Mechanistically, the metabolic benefits of 2076A might have been accounted
      for by the increased insulin sensitivity and suppression of genes that are
      involved in hepatic gluconeogenesis and lipogenesis. In summary, we have
      uncovered a new class of nonsteroidal FXR agonist that shows promise in treating
      NAFLD and the associated metabolic syndrome.

PMID- 28739575
TI  - FDA Regulatory Perspectives for Studies on Hemodialysis Vascular Access.
AB  - In an effort to foster innovation and new product development, the American
      Society of Nephrology and the US Food and Drug Administration partnered to form
      the Kidney Health Initiative in 2012. Part of the Kidney Health Initiative's
      mission is to foster development of therapies by creating a collaborative
      environment where the US Food and Drug Administration and the greater nephrology
      community can interact to optimize product evaluation. This particular Kidney
      Health Initiative project focused on products related to hemodialysis vascular
      access, with the goal of clarifying appropriate trial end points that could
      subsequently inform clinical, regulatory, and coverage decisions. Both the lack
      of common definitions and the lack of consensus on trial end points have been
      viewed as barriers to innovation in this area. Toward this end, the Kidney Health
      Initiative convened teams of expert stakeholders to address these issues for each
      major vascular access category (arteriovenous grafts, arteriovenous fistulas, and
      central venous catheters), and each team provided recommendations. This
      commentary provides an overview of the US Food and Drug Administration centers
      that regulate hemodialysis vascular access and certain laws and regulations that
      affect these products as well as our perspectives on some of the issues raised
      and end points proposed by the Kidney Health Initiative teams. The standardized
      definitions and clinical trial end points proposed by the teams represent an
      important step forward to improve innovation in this area.

PMID- 28739576
TI  - Temporal Trends and Factors Associated with Home Hemodialysis Technique Survival
      in Canada.
AB  - BACKGROUND AND OBJECTIVES: The last 15 years has seen growth in home hemodialysis
      (HD) utilization in Canada owing to reports of improved outcomes relative to
      patients on conventional in-center HD. What effect growth has had on home HD
      technique and patient survival during this period is not known. DESIGN, SETTINGS,
      PARTICIPANTS, & MEASUREMENTS: We compared the risk of home HD technique failure,
      mortality, and the composite outcome among three incident cohorts of patients on
      home HD in Canada: 1996-2002, 2003-2007, and 2008-2012. A multivariable piece
      wise exponential model was used to evaluate all outcomes using inverse
      probability of treatment and censoring weights. RESULTS: A total of 1869 incident
      patients on home HD were identified from the Canadian Organ Replacement Register.
      Relative to those treated between 2003 and 2007 (n=568), the risk of home HD
      technique failure was similar between patients treated between 1996 and 2002
      (n=233; adjusted hazard ratio [AHR], 1.39; 95% confidence interval [95% CI], 0.78
      to 2.46) but higher among incident patients on home HD treated between 2008 and
      2012 (n=1068; AHR, 1.51; 95% CI, 1.06 to 2.15). Relative to patients treated
      between 2003 and 2007, adjusted mortality was similar among those treated between
      2008 and 2012 (AHR, 0.83; 95% CI, 0.58 to 1.19) and those treated between 1996
      and 2002 (AHR, 0.67; 95% CI, 0.38 to 1.21). The risk of the composite outcome of
      death and technique failure was similar across cohorts, as was the risk of
      receiving a kidney transplant. Increasing age, diabetes as a comorbidity, and
      smoking status were associated with an increased risk of death as well as the
      composite outcome. Medium-sized facilities had a lower risk of death, technique
      failure, and the composite outcome compared with larger facilities. CONCLUSIONS:
      A higher risk of technique failure was seen in the most contemporary era. Further
      characterization of the risk factors for, and causes of technique failure is
      needed to develop strategies to improve patient retention on home HD.

PMID- 28739577
TI  - Common pitfalls and mistakes in the set-up, analysis and interpretation of
      results in network meta-analysis: what clinicians should look for in a published
      article.
AB  - OBJECTIVE: Several tools have been developed to evaluate the extent to which the
      findings from a network meta-analysis would be valid; however, applying these
      tools is a time-consuming task and often requires specific expertise. Clinicians
      have little time for critical appraisal, and they need to understand the key
      elements that help them select network meta-analyses that deserve further
      attention, optimising time and resources. This paper is aimed at providing a
      practical framework to assess the methodological robustness and reliability of
      results from network meta-analysis. METHODS: As a working example, we selected a
      network meta-analysis about drug treatments for generalised anxiety disorder,
      which was published in 2011 in the British Medical Journal. The same network meta
      analysis was previously used to illustrate the potential of this methodology in a
      methodological paper published in JAMA. RESULTS: We reanalysed the 27 studies
      included in this network following the methods reported in the original article
      and compared our findings with the published results. We showed how different
      methodological approaches and the presentation of results can affect conclusions
      from network meta-analysis. We divided our results into three sections, according
      to the specific issues that should always be addressed in network meta-analysis:
      (1) understanding the evidence base, (2) checking the statistical analysis and
      (3) checking the reporting of findings. CONCLUSIONS: The validity of the results
      from network meta-analysis depends on the plausibility of the transitivity
      assumption. The risk of bias introduced by limitations of individual studies must
      be considered first and judgement should be used to infer about the plausibility
      of transitivity. Inconsistency exists when treatment effects from direct and
      indirect evidence are in disagreement. Unlike transitivity, inconsistency can be
      always evaluated statistically, and it should be specifically investigated and
      reported in the published paper. Network meta-analysis allows researchers to list
      treatments in preferential order; however, in this paper we demonstrated that
      rankings could be misleading if based on the probability of being the best.
      Clinicians should always be interested in the effect sizes rather than the naive
      rankings.

PMID- 28739578
TI  - Applying deep neural networks to unstructured text notes in electronic medical
      records for phenotyping youth depression.
AB  - BACKGROUND: We report a study of machine learning applied to the phenotyping of
      psychiatric diagnosis for research recruitment in youth depression, conducted
      with 861 labelled electronic medical records (EMRs) documents. A model was built
      that could accurately identify individuals who were suitable candidates for a
      study on youth depression. OBJECTIVE: Our objective was a model to identify
      individuals who meet inclusion criteria as well as unsuitable patients who would
      require exclusion. METHODS: Our methods included applying a system that coded the
      EMR documents by removing personally identifying information, using two
      psychiatrists who labelled a set of EMR documents (from which the 861 came),
      using a brute force search and training a deep neural network for this task.
      FINDINGS: According to a cross-validation evaluation, we describe a model that
      had a specificity of 97% and a sensitivity of 45% and a second model with a
      specificity of 53% and a sensitivity of 89%. We combined these two models into a
      third one (sensitivity 93.5%; specificity 68%; positive predictive value
      (precision) 77%) to generate a list of most suitable candidates in support of
      research recruitment. CONCLUSION: Our efforts are meant to demonstrate the
      potential for this type of approach for patient recruitment purposes but it
      should be noted that a larger sample size is required to build a truly reliable
      recommendation system. CLINICAL IMPLICATIONS: Future efforts will employ
      alternate neural network algorithms available and other machine learning methods.

PMID- 28739579
TI  - The prospective validation of the Modified Physiological Triage Tool (MPTT): an
      evidence-based approach to major incident triage.
AB  - INTRODUCTION: Triage is a key principle in the effective management of major
      incidents. There is limited evidence to support existing triage tools, with a
      number of studies demonstrating poor performance at predicting the need for a
      life-saving intervention. The Modified Physiological Triage Tool (MPTT) is a
      novel triage tool derived using logistic regression, and in retrospective data
      sets has shown optimum performance at predicting the need for life-saving
      intervention. MATERIALS AND METHODS: Physiological data and interventions were
      prospectively collected for consecutive adult patients with trauma (>18 years)
      presenting to the emergency department at Camp Bastion, Afghanistan, between
      March and September 2011. Patients were considered priority 1 (P1) if they
      received one or more interventions from a previously defined list. Patients were
      triaged using existing triage tools and the MPTT. Performance was measured using
      sensitivity and specificity, and a McNemar test with Bonferroni calculation was
      applied for tools with similar performance. RESULTS: The study population
      comprised 357 patients, of whom 214 (59.9%) were classed as P1. The MPTT
      (sensitivity: 83.6%, 95% CI 78.0% to 88.3%; specificity: 51.0%, 95% CI 42.6% to
      59.5%) outperformed all existing triage tools at predicting the need for life
      saving intervention, with a 19.6% absolute reduction in undertriage compared with
      the existing Military Sieve. The improvement in undertriage comes at the expense
      of overtriage; rates of overtriage were 11.6% higher with the MPTT than the
      Military Sieve. Using a McNemar test, a statistically significant (p<0.001)
      improvement in overall performance was demonstrated, supporting the use of the
      MPTT over the Military Sieve. DISCUSSION AND CONCLUSIONS: The MPTT outperforms
      all existing triage tools at predicting the need for life-saving intervention,
      with the lowest rates of undertriage while maintaining acceptable levels of
      overtriage. Having now been validated on both military and civilian cohorts, we
      recommend that the major incident community consider adopting the MPTT for the
      purposes of primary triage.

PMID- 28739580
TI  - Structural insights into transcription initiation by yeast RNA polymerase I.
AB  - In eukaryotic cells, RNA polymerase I (Pol I) synthesizes precursor ribosomal RNA
      (pre-rRNA) that is subsequently processed into mature rRNA. To initiate
      transcription, Pol I requires the assembly of a multi-subunit pre-initiation
      complex (PIC) at the ribosomal RNA promoter. In yeast, the minimal PIC includes
      Pol I, the transcription factor Rrn3, and Core Factor (CF) composed of subunits
      Rrn6, Rrn7, and Rrn11. Here, we present the cryo-EM structure of the 18-subunit
      yeast Pol I PIC bound to a transcription scaffold. The cryo-EM map reveals an
      unexpected arrangement of the DNA and CF subunits relative to Pol I. The upstream
      DNA is positioned differently than in any previous structures of the Pol II PIC.
      Furthermore, the TFIIB-related subunit Rrn7 also occupies a different location
      compared to the Pol II PIC although it uses similar interfaces as TFIIB to
      contact DNA. Our results show that although general features of eukaryotic
      transcription initiation are conserved, Pol I and Pol II use them differently in
      their respective transcription initiation complexes.

PMID- 28739581
TI  - A novel prognostic model for transplant-free survival in primary sclerosing
      cholangitis.
AB  - OBJECTIVE: Most prognostic models for primary sclerosing cholangitis (PSC) are
      based on patients referred to tertiary care and may not be applicable for the
      majority of patients with PSC. The aim of this study was to construct and
      externally validate a novel, broadly applicable prognostic model for transplant
      free survival in PSC, based on a large, predominantly population-based cohort
      using readily available variables. DESIGN: The derivation cohort consisted of 692
      patients with PSC from the Netherlands, the validation cohort of 264 patients
      with PSC from the UK. Retrospectively, clinical and biochemical variables were
      collected. We derived the prognostic index from a multivariable Cox regression
      model in which predictors were selected and parameters were estimated using the
      least absolute shrinkage and selection operator. The composite end point of PSC
      related death and liver transplantation was used. To quantify the models'
      predictive value, we calculated the C-statistic as discrimination index and
      established its calibration accuracy by comparing predicted curves with Kaplan
      Meier estimates. RESULTS: The final model included the variables: PSC subtype,
      age at PSC diagnosis, albumin, platelets, aspartate aminotransferase, alkaline
      phosphatase and bilirubin. The C-statistic was 0.68 (95% CI 0.51 to 0.85).
      Calibration was satisfactory. The model was robust in the sense that the C
      statistic did not change when prediction was based on biochemical variables
      collected at follow-up. CONCLUSION: The Amsterdam-Oxford model for PSC showed
      adequate performance in estimating PSC-related death and/or liver transplant in a
      predominantly population-based setting. The transplant-free survival probability
      can be recalculated when updated biochemical values are available.

PMID- 28739582
TI  - Gain Modulation as a Mechanism for Coding Depth from Motion Parallax in Macaque
      Area MT.
AB  - Observer translation produces differential image motion between objects that are
      located at different distances from the observer's point of fixation [motion
      parallax (MP)]. However, MP can be ambiguous with respect to depth sign (near vs
      far), and this ambiguity can be resolved by combining retinal image motion with
      signals regarding eye movement relative to the scene. We have previously
      demonstrated that both extra-retinal and visual signals related to smooth eye
      movements can modulate the responses of neurons in area MT of macaque monkeys,
      and that these modulations generate neural selectivity for depth sign. However,
      the neural mechanisms that govern this selectivity have remained unclear. In this
      study, we analyze responses of MT neurons as a function of both retinal velocity
      and direction of eye movement, and we show that smooth eye movements modulate MT
      responses in a systematic, temporally precise, and directionally specific manner
      to generate depth-sign selectivity. We demonstrate that depth-sign selectivity is
      primarily generated by multiplicative modulations of the response gain of MT
      neurons. Through simulations, we further demonstrate that depth can be estimated
      reasonably well by a linear decoding of a population of MT neurons with response
      gains that depend on eye velocity. Together, our findings provide the first
      mechanistic description of how visual cortical neurons signal depth from
      MP.SIGNIFICANCE STATEMENT Motion parallax is a monocular cue to depth that
      commonly arises during observer translation. To compute from motion parallax
      whether an object appears nearer or farther than the point of fixation requires
      combining retinal image motion with signals related to eye rotation, but the
      neurobiological mechanisms have remained unclear. This study provides the first
      mechanistic account of how this interaction takes place in the responses of
      cortical neurons. Specifically, we show that smooth eye movements modulate the
      gain of responses of neurons in area MT in a directionally specific manner to
      generate selectivity for depth sign from motion parallax. We also show, through
      simulations, that depth could be estimated from a population of such gain
      modulated neurons.

PMID- 28739583
TI  - Tonic or Phasic Stimulation of Dopaminergic Projections to Prefrontal Cortex
      Causes Mice to Maintain or Deviate from Previously Learned Behavioral Strategies.
AB  - Dopamine neurons in the ventral tegmental area (VTA) encode reward prediction
      errors and can drive reinforcement learning through their projections to
      striatum, but much less is known about their projections to prefrontal cortex
      (PFC). Here, we studied these projections and observed phasic VTA-PFC fiber
      photometry signals after the delivery of rewards. Next, we studied how
      optogenetic stimulation of these projections affects behavior using conditioned
      place preference and a task in which mice learn associations between cues and
      food rewards and then use those associations to make choices. Neither phasic nor
      tonic stimulation of dopaminergic VTA-PFC projections elicited place preference.
      Furthermore, substituting phasic VTA-PFC stimulation for food rewards was not
      sufficient to reinforce new cue-reward associations nor maintain previously
      learned ones. However, the same patterns of stimulation that failed to reinforce
      place preference or cue-reward associations were able to modify behavior in other
      ways. First, continuous tonic stimulation maintained previously learned cue
      reward associations even after they ceased being valid. Second, delivering phasic
      stimulation either continuously or after choices not previously associated with
      reward induced mice to make choices that deviated from previously learned
      associations. In summary, despite the fact that dopaminergic VTA-PFC projections
      exhibit phasic increases in activity that are time locked to the delivery of
      rewards, phasic activation of these projections does not necessarily reinforce
      specific actions. Rather, dopaminergic VTA-PFC activity can control whether mice
      maintain or deviate from previously learned cue-reward associations.SIGNIFICANCE
      STATEMENT Dopaminergic inputs from ventral tegmental area (VTA) to striatum
      encode reward prediction errors and reinforce specific actions; however, it is
      currently unknown whether dopaminergic inputs to prefrontal cortex (PFC) play
      similar or distinct roles. Here, we used bulk Ca2+ imaging to show that
      unexpected rewards or reward-predicting cues elicit phasic increases in the
      activity of dopaminergic VTA-PFC fibers. However, in multiple behavioral
      paradigms, we failed to observe reinforcing effects after stimulation of these
      fibers. In these same experiments, we did find that tonic or phasic patterns of
      stimulation caused mice to maintain or deviate from previously learned cue-reward
      associations, respectively. Therefore, although they may exhibit similar patterns
      of activity, dopaminergic inputs to striatum and PFC can elicit divergent
      behavioral effects.

PMID- 28739585
TI  - The Burdens and Uncertainties of Doing What One Should Do.
AB  - Despite FDA approval of drugs to reduce the risk of breast cancer in women at
      increased risk, uptake of these drugs has been poor despite the publication of
      numerous studies that demonstrate both their effectives and safety. National
      organizations have made recommendations for their use, but both physicians and
      their patients do not fully understand either breast cancer risk factors or risk
      assessment or the indications for using risk-reducing agents. Histologically
      predisposing conditions, such as ductal or lobular atypia and lobular carcinoma
      in situ, impart particularly high risks of developing subsequent invasive breast
      cancer. Resources should be committed to both provider and patient education to
      reduce the risk of breast cancer in women who are at increased risk. Cancer Prev
      Res; 10(8); 1-3. (c)2017 AACR.

PMID- 28739584
TI  - Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked
      to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females.
AB  - The development of robust laboratory procedures for acute stress induction over
      the last decades has greatly advanced our understanding of stress responses in
      humans and their underlying neurobiological mechanisms. Nevertheless, attempts to
      uncover linear relationships among endocrine, neural, and affective responses to
      stress have generally yielded inconsistent results. Here, 79 healthy females
      completed a well established laboratory procedure of acute stress induction that
      was modified to prolong its effect. Endocrinological and subjective affect
      assessments revealed stress-induced increases in cortisol release and negative
      affect that persisted 65 and 100 min after stress onset, respectively, confirming
      a relatively prolonged acute stress induction. Applying latent class linear mixed
      modeling on individuals' patterns of cortisol responses identified three distinct
      trajectories of cortisol response: the hyper-response (n = 10), moderate-response
      (n = 21), and mild-response (n = 48) groups. Notably, whereas all three groups
      exhibited a significant stress-induced increase in cortisol release and negative
      affect, the hyper-response and mild-response groups both reported more negative
      affect relative to the moderate-response group. Structural MRI revealed no group
      differences in hippocampal and amygdala volumes, yet a continuous measure of
      cortisol response (area under the curve) showed that high and low levels of
      stress-induced cortisol release were associated with less hippocampal gray matter
      volume compared with moderate cortisol release. Together, these results suggest
      that distinct trajectories of cortisol response to prolonged acute stress among
      healthy females may not be captured by conventional linear analyses; instead,
      quadratic relations may better describe links between cortisol response to stress
      and affective responses, as well as hippocampal structural
      variability.SIGNIFICANCE STATEMENT Despite substantial research, it is unclear
      whether and how individual neuroendocrine stress response patterns are linked to
      affective responses to stress and structural variability in neuroendocrine
      regulatory brain regions. By applying latent class linear mixed modeling on
      individuals' patterns of cortisol responses to a prolonged acute stressor, we
      identified three distinct trajectories of cortisol response. Relative to the
      group showing a moderate cortisol response, groups characterized by hyper and
      mild cortisol response were both associated with more negative affect. Moreover,
      a continuous measure of cortisol response showed that high and low levels of
      stress-induced cortisol release correlated with reduced hippocampal gray matter
      volume. Given that neuroendocrine stress responses are conceptualized as
      biomarkers of stress susceptibility, these insights may have clinical
      implications.

PMID- 28739586
TI  - Immortal.

PMID- 28739587
TI  - Tonio: Telling Time.

PMID- 28739588
TI  - N-terminal pyroglutamate formation in CX3CL1 is essential for its full biologic
      activity.
AB  - CX3CL1 (fractalkine) is a unique member of the CX3C chemokine family and mediates
      both adhesion and cell migration in inflammatory processes. Frequently, the
      activity of chemokines depends on a modified N-terminus as described for the N
      terminus of CCL2 modified to a pGlu- (pyroglutamate) residue by QC (glutaminyl
      cyclase) activity. Here, we assess the role of the pGlu-modified residue of the
      CX3CL1 chemokine domain in human endothelial and smooth muscle cells. For the
      first time, we demonstrated using MS that QC (QPCT, gene name of QC) or its
      isoenzyme isoQC (iso-glutaminyl cyclase) (QPCTL, gene name of isoQC) catalyse the
      formation of N-terminal-modified pGlu-CX3CL1. Expression of QPCT is co-regulated
      with its substrates CCL2 and CX3CL1 in HUVECs (human umbilical vein endothelial
      cells) and HCASMCs (human coronary artery smooth muscle cells) upon stimulation
      with TNF-alpha and IL-1beta whereas QPCTL expression is not affected. By
      contrast, inhibition of the NF-kappaB pathway using an IKK2 inhibitor decreased
      the expression of the co-regulated targets QPCT, CCL2, and CX3CL1 Furthermore,
      RNAi-mediated inhibition of QPCT expression resulted in a reduction in CCL2 and
      CX3CL1 mRNA. In HCASMCs, N-terminal-modified pGlu1-CX3CL1 induced a significant
      stronger effect on phosphorylation of ERK (extracellular signal regulated kinase)
      1/2, Akt (protein kinase B), and p38 (p38 mitogen-activated protein kinase)
      kinases than the immature Gln1-CX3CL1 in a time- and concentration-dependent
      manner. Furthermore, pGlu1-CX3CL1 affected the expression of CCL2, CX3CL1, and
      the adhesion molecule ICAM1/CD54 (intercellular adhesion molecule-1) inducing in
      higher expression level compared with its Gln1-variant in both HCASMCs and
      HUVECs. These results strongly suggest that QC-catalysed N-terminal pGlu
      formation of CX3CL1 is important for the stability or the interaction with its
      receptor and opens new insights into the function of QC in inflammation.

PMID- 28739589
TI  - Association of calcium/calmodulin-dependent protein kinase kinase1 rs7214723
      polymorphism with lung cancer risk in a Chinese population.
AB  - Calcium/calmodulin-dependent protein kinase kinase1 (CAMKK1) could specially
      recognize and activate Calcium/calmodulin-dependent protein kinase (CAMK) I and
      IV. Furthermore, The activation of CAMK showed positively correlation with
      proliferation of lung cancer (LC). In addition, A genome-wide association study
      has identified rs7214723 (E375G) in the CAMKK1 gene as a susceptibility locus for
      LC in the UK population. Therefore, we conducted a case-control study involving
      320 LC patients and 320 controls to validate this conclusion in a Chinese
      population. Genotyping was performed using a custom-by-design 48-Plex single
      nucleotide polymorphism (SNP) ScanTM Kit. Our results indicate that the
      individuals with CC genotype of rs7214723 polymorphism had the higher risk of LC
      than those who carried TT genotype. Moreover, CAMKK1 rs7214723 polymorphism
      showed positively correlation with the elevated risk of LC in the allelic model
      and recessive model, but not in the dominant model. Stratified analysis further
      confirmed this significant association in male groups and smokers. In conclusion,
      CAMKK1 rs7214723 polymorphism may be associated with the increased risk of LC.
      However, larger studies with more diverse ethnic populations are needed to
      confirm these results.

PMID- 28739591
TI  - Role for academic institutions and think tanks in speeding progress on
      sustainable development goals.

PMID- 28739590
TI  - Mast Cells Granular Contents Are Crucial for Deep Vein Thrombosis in Mice.
AB  - RATIONALE: Deep vein thrombosis (DVT) and its complication pulmonary embolism
      have high morbidity reducing quality of life and leading to death. Cellular
      mechanisms of DVT initiation remain poorly understood. OBJECTIVE: We sought to
      determine the role of mast cells (MCs) in DVT initiation and validate MCs as a
      potential target for DVT prevention. METHODS AND RESULTS: In a mouse model, DVT
      was induced by partial ligation (stenosis) of the inferior vena cava. We
      demonstrated that 2 strains of mice deficient for MCs were completely protected
      from DVT. Adoptive transfer of in vitro differentiated MCs restored thrombosis.
      MCs were present in the venous wall, and the number of granule-containing MCs
      decreased with thrombosis. Pharmacological depletion of MCs granules or
      prevention of MC degranulation also reduced DVT. Basal plasma levels of von
      Willebrand factor and recruitment of platelets to the inferior vena cava wall
      after DVT induction were reduced in MC-deficient mice. Stenosis application
      increased plasma levels of soluble P-selectin in wild-type but not in MC
      deficient mice. MC releasate elevated ICAM-1 (intercellular adhesion molecule-1)
      expression on HUVEC (human umbilical vein endothelial cells) in vitro. Topical
      application of compound 48/80, an MC secretagogue, or histamine, a Weibel-Palade
      body secretagogue from MCs, potentiated DVT in wild-type mice, and histamine
      restored thrombosis in MC-deficient animals. CONCLUSIONS: MCs exacerbate DVT
      likely through endothelial activation and Weibel-Palade body release, which is,
      at least in part, mediated by histamine. Because MCs do not directly contribute
      to normal hemostasis, they can be considered potential targets for prevention of
      DVT in humans.

PMID- 28739592
TI  - Defining the Kinetics, Phenotype, and Function of T Cells Induced by
      Mycobacterium tuberculosis: Pillar of Immunity to Tuberculosis.

PMID- 28739593
TI  - Pillars Article: The Kinetics of Emergence and Loss of Mediator T Lymphocytes
      Acquired in Response to Infection with Mycobacterium Tuberculosis. J. Immunol.
      1987. 138: 293-298.

PMID- 28739595
TI  - Retraction: Hypoxia-Inducible Factor (HIF) 1alpha Accumulation and HIF Target
      Gene Expression Are Impaired after Induction of Endotoxin Tolerance.

PMID- 28739594
TI  - Here, There, and Anywhere? Arguments for and against the Physical Plasma Cell
      Survival Niche.
AB  - To maintain Ab titers, individual plasma cells must survive for extended periods,
      perhaps even for the life of the host. Although it is clear that plasma cell
      survival requires cell extrinsic signals, the nature and source of these signals
      remains open for debate. It is commonly postulated that plasma cells only gain
      access to these signals within specialized regulatory microenvironments, or
      niches, in the bone marrow or in the gut. In this review we discuss current
      concepts and information surrounding plasma cell survival niches, and consider
      two opposing models to explain long-term serologic immunity.

PMID- 28739596
TI  - Correction: DNA Repair Interacts with Autophagy To Regulate Inflammatory
      Responses to Pulmonary Hyperoxia.

PMID- 28739597
TI  - A Large Deletion in the NSDHL Gene in Labrador Retrievers with a Congenital
      Cornification Disorder.
AB  - In heterozygous females affected by an X-linked skin disorder, lesions often
      appear in a characteristic pattern, the so-called Blaschko's lines. We
      investigated a female Labrador Retriever and her crossbred daughter, which both
      showed similar clinical lesions that followed Blaschko's lines. The two male
      littermates of the affected daughter had died at birth, suggesting a monogenic X
      chromosomal semidominant mode of inheritance. Whole genome sequencing of the
      affected daughter, and subsequent automated variant filtering with respect to 188
      nonaffected control dogs of different breeds, revealed 332 hetero-zygous variants
      on the X-chromosome private to the affected dog. None of these variants was
      protein-changing. By visual inspection of candidate genes located on the X
      chromosome, we identified a large deletion in the NSDHL gene, encoding NAD(P)
      dependent steroid dehydrogenase-like, a 3beta-hydroxysteroid dehydrogenase
      involved in cholesterol biosynthesis. The deletion spanned >14 kb, and included
      the last three exons of the NSDHL gene. By PCR and fragment length analysis, we
      confirmed the presence of the variant in both affected dogs, and its absence in
      50 control Labrador Retrievers. Variants in the NSDHL gene cause CHILD syndrome
      in humans, and the bare patches (Bpa) and striated (Str) phenotypes in mice.
      Taken together, our genetic data and the known role of NSDHL in X-linked skin
      disorders strongly suggest that the identified structural variant in the NSDHL
      gene is causative for the phenotype in the two affected dogs.

PMID- 28739598
TI  - Sequence-Based Mapping and Genome Editing Reveal Mutations in Stickleback Hps5
      Cause Oculocutaneous Albinism and the casper Phenotype.
AB  - Here, we present and characterize the spontaneous X-linked recessive mutation
      casper, which causes oculocutaneous albinism in threespine sticklebacks
      (Gasterosteus aculeatus). In humans, Hermansky-Pudlak syndrome results in
      pigmentation defects due to disrupted formation of the melanin-containing
      lysosomal-related organelle (LRO), the melanosome. casper mutants display not
      only reduced pigmentation of melanosomes in melanophores, but also reductions in
      the iridescent silver color from iridophores, while the yellow pigmentation from
      xanthophores appears unaffected. We mapped casper using high-throughput
      sequencing of genomic DNA from bulked casper mutants to a region of the
      stickleback X chromosome (chromosome 19) near the stickleback ortholog of
      Hermansky-Pudlak syndrome 5 (Hps5). casper mutants have an insertion of a single
      nucleotide in the sixth exon of Hps5, predicted to generate an early frameshift.
      Genome editing using CRISPR/Cas9 induced lesions in Hps5 and phenocopied the
      casper mutation. Injecting single or paired Hps5 guide RNAs revealed higher
      incidences of genomic deletions from paired guide RNAs compared to single gRNAs.
      Stickleback Hps5 provides a genetic system where a hemizygous locus in XY males
      and a diploid locus in XX females can be used to generate an easily scored
      visible phenotype, facilitating quantitative studies of different genome editing
      approaches. Lastly, we show the ability to better visualize patterns of
      fluorescent transgenic reporters in Hps5 mutant fish. Thus, Hps5 mutations
      present an opportunity to study pigmented LROs in the emerging stickleback model
      system, as well as a tool to aid in assaying genome editing and visualizing
      enhancer activity in transgenic fish.

PMID- 28739599
TI  - Evolutionary Dynamics of Male Reproductive Genes in the Drosophila virilis
      Subgroup.
AB  - Postcopulatory sexual selection (PCSS) is a potent evolutionary force that can
      drive rapid changes of reproductive genes within species, and thus has the
      potential to generate reproductive incompatibilities between species. Male
      seminal fluid proteins (SFPs) are major players in postmating interactions, and
      are important targets of PCSS in males. The virilis subgroup of Drosophila
      exhibits strong interspecific gametic incompatibilities, and can serve as a model
      to study the genetic basis of PCSS and gametic isolation. However, reproductive
      genes in this group have not been characterized. Here we utilize short-read RNA
      sequencing of male reproductive organs to examine the evolutionary dynamics of
      reproductive genes in members of the virilis subgroup: D. americana, D. lummei,
      D. novamexicana, and D. virilis We find that the majority of male reproductive
      transcripts are testes-biased, accounting for ~15% of all annotated genes.
      Ejaculatory bulb (EB)-biased transcripts largely code for lipid metabolic
      enzymes, and contain orthologs of the D. melanogaster EB protein, Peb-me, which
      is involved in mating-plug formation. In addition, we identify 71 candidate SFPs,
      and show that this gene set has the highest rate of nonsynonymous codon
      substitution relative to testes- and EB-biased genes. Furthermore, we identify
      orthologs of 35 D. melanogaster SFPs that have conserved accessory gland
      expression in the virilis group. Finally, we show that several of the SFPs that
      have the highest rate of nonsynonymous codon substitution reside on chromosomal
      regions, which contributes to paternal gametic incompatibility between species.
      Our results show that SFPs rapidly diversify in the virilis group, and suggest
      that they likely play a role in PCSS and/or gametic isolation.

PMID- 28739600
TI  - Whole-Genome Sequencing and Concordance Between Antimicrobial Susceptibility
      Genotypes and Phenotypes of Bacterial Isolates Associated with Bovine Respiratory
      Disease.
AB  - Extended laboratory culture and antimicrobial susceptibility testing timelines
      hinder rapid species identification and susceptibility profiling of bacterial
      pathogens associated with bovine respiratory disease, the most prevalent cause of
      cattle mortality in the United States. Whole-genome sequencing offers a culture
      independent alternative to current bacterial identification methods, but requires
      a library of bacterial reference genomes for comparison. To contribute new
      bacterial genome assemblies and evaluate genetic diversity and variation in
      antimicrobial resistance genotypes, whole-genome sequencing was performed on
      bovine respiratory disease-associated bacterial isolates (Histophilus somni,
      Mycoplasma bovis, Mannheimia haemolytica, and Pasteurella multocida) from dairy
      and beef cattle. One hundred genomically distinct assemblies were added to the
      NCBI database, doubling the available genomic sequences for these four species.
      Computer-based methods identified 11 predicted antimicrobial resistance genes in
      three species, with none being detected in M. bovis While computer-based analysis
      can identify antibiotic resistance genes within whole-genome sequences
      (genotype), it may not predict the actual antimicrobial resistance observed in a
      living organism (phenotype). Antimicrobial susceptibility testing on 64 H. somni,
      M. haemolytica, and P. multocida isolates had an overall concordance rate between
      genotype and phenotypic resistance to the associated class of antimicrobials of
      72.7% (P < 0.001), showing substantial discordance. Concordance rates varied
      greatly among different antimicrobial, antibiotic resistance gene, and bacterial
      species combinations. This suggests that antimicrobial susceptibility phenotypes
      are needed to complement genomically predicted antibiotic resistance gene
      genotypes to better understand how the presence of antibiotic resistance genes
      within a given bacterial species could potentially impact optimal bovine
      respiratory disease treatment and morbidity/mortality outcomes.

PMID- 28739601
TI  - Buddleja thyrsoides Lam. crude extract presents antinociceptive effect on an
      arthritic pain model in mice.
AB  - Arthritis is a chronic inflammatory disease which reduces the life quality of
      affected individuals. Therapeutic tools used for treating inflammatory pain are
      associated with several undesirable effects. Buddleja thyrsoides Lam., known as
      'Barbasco' or 'Cambara', is mostly used in several disorders and possesses
      antirheumatic, anti-inflammatory, and analgesic properties. Here, we investigated
      the antinociceptive and anti-inflammatory effects of the B. thyrsoides crude
      extract applied orally and topically in acute pain models and an arthritic pain
      model induced by complete Freund's adjuvant (CFA) paw injection in male mice (25
      30 g). The high-performance liquid chromatography (HPLC) of the B. thyrsoides
      extract crude revealed the presence of the lupeol, stigmasterol, and beta
      sitosterol. The stability study of the B. thyrsoides gel did not show relevant
      changes at low temperatures. The oral treatment with the B. thrysoides extract
      prevented the capsaicin-induced spontaneous nociception and the acetic acid
      induced abdominal writhing, but did not alter the thermal threshold in the tail
      immersion test. The B. thyrsoides antinociceptive effect was not reversed by
      naloxone in the capsaicin test. The B. thyrsoides oral or topical treatment
      reversed the CFA-induced mechanical allodynia and thermal hyperalgesia with
      maximum inhibition (Imax) of 69 +/- 6 and 68 +/- 5% as well as 78 +/- 15 and 87
      +/- 12%, respectively. Moreover, the topical but not oral treatment inhibited the
      CFA-induced cell infiltration, but did not reduce the paw edema significantly.
      The oral treatment with B. thyrsoides did not cause adverse effects. These
      findings suggest that the oral or topical treatment with B. thyrsoides presents
      antinociceptive actions in an arthritic pain model without causing adverse
      effects.

PMID- 28739602
TI  - Loss of prion protein is associated with the development of insulin resistance
      and obesity.
AB  - Prion protein (PrPC) was initially described due to its involvement in
      transmissible spongiform encephalopathies. It was subsequently demonstrated to be
      a cell surface molecule involved in many physiological processes, such as vesicle
      trafficking. Here, we investigated the roles of PrPC in the response to insulin
      and obesity development. Two independent PrPC knockout (KO) and one PrPC
      overexpressing (TG20) mouse models were fed high-fat diets, and the development
      of insulin resistance and obesity was monitored. PrPC KO mice fed high-fat diets
      presented all of the symptoms associated with the development of insulin
      resistance: hyperglycemia, hyperinsulinemia, and obesity. Conversely, TG20
      animals fed high-fat diets showed reduced weight and insulin resistance.
      Accordingly, the expression of peroxisome proliferator-activated receptor gamma
      (PPARgamma) was reduced in PrPC KO mice and increased in TG20 animals. PrPC KO
      cells also presented reduced glucose uptake upon insulin stimulation, due to
      reduced translocation of the glucose transporter Glut4. Thus, our results suggest
      that PrPC reflects susceptibility to the development of insulin resistance and
      metabolic syndrome.

PMID- 28739603
TI  - Novel in vitro booster vaccination to rapidly generate antigen-specific human
      monoclonal antibodies.
AB  - Vaccines remain the most effective tool to prevent infectious diseases. Here, we
      introduce an in vitro booster vaccination approach that relies on antigen
      dependent activation of human memory B cells in culture. This stimulation induces
      antigen-specific B cell proliferation, differentiation of B cells into plasma
      cells, and robust antibody secretion after a few days of culture. We validated
      this strategy using cells from healthy donors to retrieve human antibodies
      against tetanus toxoid and influenza hemagglutinin (HA) from H1N1 and newly
      emergent subtypes such as H5N1 and H7N9. Anti-HA antibodies were cross-reactive
      against multiple subtypes, and some showed neutralizing activity. Although these
      antibodies may have arisen as a result of previous influenza infection, we also
      obtained gp120-reactive antibodies from non-HIV-infected donors, indicating that
      we can generate antibodies without prior antigenic exposure. Overall, our novel
      approach can be used to rapidly produce therapeutic antibodies and has the
      potential to assess the immunogenicity of candidate antigens, which could be
      exploited in future vaccine development.

PMID- 28739604
TI  - S1PR1 on tumor-associated macrophages promotes lymphangiogenesis and metastasis
      via NLRP3/IL-1beta.
AB  - Metastasis is the primary cause of cancer death. The inflammatory tumor
      microenvironment contributes to metastasis, for instance, by recruiting blood and
      lymph vessels. Among tumor-infiltrating immune cells, tumor-associated
      macrophages (TAMs) take a center stage in promoting both tumor angiogenesis and
      metastatic spread. We found that genetic deletion of the S1P receptor 1 (S1pr1)
      alone in CD11bhi CD206+ TAMs infiltrating mouse breast tumors prevents pulmonary
      metastasis and tumor lymphangiogenesis. Reduced lymphangiogenesis was also
      observed in the nonrelated methylcholanthrene-induced fibrosarcoma model.
      Transcriptome analysis of isolated TAMs from both entities revealed reduced
      expression of the inflammasome component Nlrp3 in S1PR1-deficient TAMs.
      Macrophage-dependent lymphangiogenesis in vitro was triggered upon inflammasome
      activation and required both S1PR1 signaling and IL-1beta production. Finally,
      NLRP3 expression in tumor-infiltrating macrophages correlated with survival,
      lymph node invasion, and metastasis of mammary carcinoma patients. Conceptually,
      our study indicates an unappreciated role of the NLRP3 inflammasome in promoting
      metastasis via the lymphatics downstream of S1PR1 signaling in macrophages.

PMID- 28739605
TI  - Genetic variation in the gene LRP2 increases relapse risk in multiple sclerosis.
AB  - BACKGROUND: Due to the lack of prospective studies with longitudinal data on
      relapse, past genetic studies have not attempted to identify genetic factors that
      predict relapse risk (the primary endpoint of many pivotal clinical trials
      testing the efficacy of multiple sclerosis (MS) disease-modifying drugs) at a
      genome-wide scale. METHODS: We conducted a genome-wide association analysis
      (GWAS) to identify genetic variants that predict MS relapse risk, using a three
      stage approach. First, GWAS was conducted using the southern Tasmania MS
      Longitudinal Study with 141 cases followed prospectively for a mean of 2.3 years.
      Second, GWAS was conducted using the Ausimmune Longitudinal Study with 127 cases
      having a classic first demyelinating event followed for 5 years from onset.
      Third, the top hits with p<5.0*10-6 from the first two stages were combined with
      a longitudinal US paediatric MS cohort with 181 cases followed for 5 years after
      onset. Predictors of time to relapse were evaluated by a mixed effects Cox model.
      An inverse variance fixed effects model was then used to undertake a meta
      analysis. RESULTS: In the pooled results, using these three unique longitudinal
      MS cohorts, we discovered one novel locus (LRP2; most significant single
      nucleotide polymorphism rs12988804) that reached genome-wide significance in
      predicting relapse risk (HR=2.18, p=3.30*10-8). LRP2 is expressed on the surface
      of many central nervous system cells including neurons and oligodendrocytes and
      is a critical receptor in axonal guidance. CONCLUSIONS: The finding of a genetic
      locus that has extensive effects on neuronal development and repair is of
      interest as a potential modulator of MS disease course.

PMID- 28739606
TI  - Cognitively impaired patients with heart failure may not perceive weight gain as
      a risk for decompensation.

PMID- 28739607
TI  - Skin-to-skin care is an effective and safe intervention to reduce procedural pain
      in neonates.

PMID- 28739608
TI  - Risk of injury higher in older adults with dementia than in those without.

PMID- 28739609
TI  - A national quitline service and its promotion in the mass media: modelling the
      health gain, health equity and cost-utility.
AB  - BACKGROUND: Mass media campaigns and quitlines are both important distinct
      components of tobacco control programmes around the world. But when used as an
      integrated package, the effectiveness and cost-effectiveness are not well
      described. We therefore aimed to estimate the health gain, health equity impacts
      and cost-utility of the package of a national quitline service and its promotion
      in the mass media. METHODS: We adapted an established Markov and multistate life
      table macro-simulation model. The population was all New Zealand adults in 2011.
      Effect sizes and intervention costs were based on past New Zealand quitline data.
      Health system costs were from a national data set linking individual health
      events to costs. RESULTS: The 1-year operation of the existing intervention
      package of mass media promotion and quitline service was found to be net cost
      saving to the health sector for all age groups, sexes and ethnic groups (saving
      $NZ84 million; 95%uncertainty interval 60-115 million in the base-case model). It
      also produced greater per capita health gains for Maori (indigenous) than non
      Maori (2.2 vs 0.73 quality-adjusted life-years (QALYs) per 1000 population,
      respectively). The net cost saving of the intervention was maintained in all
      sensitivity and scenario analyses for example at a discount rate of 6% and when
      the intervention effect size was quartered (given the possibility of residual
      confounding in our estimates of smoking cessation). Running the intervention for
      20 years would generate an estimated 54 000 QALYs and $NZ1.10 billion (US$0.74
      billion) in cost savings. CONCLUSIONS: The package of a quitline service and its
      promotion in the mass media appears to be an effective means to generate health
      gain, address health inequalities and save health system costs. Nevertheless, the
      role of this intervention needs to be compared with other tobacco control and
      health sector interventions, some of which may be even more cost saving.

PMID- 28739610
TI  - Silicone implant incompatibility syndrome (SIIS) in a 57-year-old woman with
      unilateral silicone breast implant.
AB  - Since the 1960s, silicone implants have been used for breast augmentations, both
      cosmetically and in reconstructive surgery. Tissue exposed to silicone can react
      with multiple adverse advents. Autoimmune/inflammatory syndrome induced by
      adjuvants due to silicone exposure from ruptured silicone implants can lead to
      different interstitial lung manifestations predominantly with granuloma
      evolvement, leading to the so-called silicone implant incompatibility syndrome
      (SIIS). This case describes a 57-year-old woman with multiple lung infiltrations
      and a left-sided breast implant. The implant had been replaced twice, once due to
      implant rupture 36 years ago. The nodular infiltrates could not be related to
      infection, malignancy, interstitial lung disease, vasculitis or connective tissue
      disorder, and it was concluded that the nodular infiltrations were of
      inflammatory origin due to an autoimmune response secondary to the silicone
      implants (SIIS). After explantation, the patient's symptoms subsided and her
      physical condition has remarkably improved.

PMID- 28739611
TI  - An unusual presentation of a benign pancreatic lesion containing amyloid.
AB  - We present a unique case of a benign pancreatic lesion which was positive for
      amyloid in a 55-year-old female patient without systemic amyloidosis. Further
      testing revealed islet-type amyloid polypeptide (or amylin), a protein found in
      various diseases such as diabetes, insulinoma and pancreatic adenocarcinoma-none
      of which was seen in our patient.

PMID- 28739612
TI  - Benign paroxysmal positional vertigo (BPPV) diagnosis and treatment in an elite
      professional football (soccer) player.
AB  - A 33-year-old male professional football player suffered from acute-onset
      dizziness following a lower limb soft tissue treatment in prone lying. Symptoms
      included spinning vertigo lasting for 30's, headache, visual vertigo and
      disorientation. Clinical examination of balance and vestibular systems confirmed
      a left posterior canalithiasis benign paroxysmal positional vertigo (BPPV) and
      excluded other central and peripheral causes of dizziness. Two cycles of a left
      Epley manoeuvre were performed. An Epley manoeuvre abolished the BPPV and negated
      the need for medication. The player was able to return to play without dizziness
      within 24 hours completely symptom free. BPPV can be successfully identified and
      treated in elite football players and they can see a return to training and games
      within 24 hours. There are no epidemiology studies for this group of elite
      athletes either male or female despite increased occupational risk factors.

PMID- 28739613
TI  - Soft tissue laceration caused by lower extremity intraosseous access insertion in
      an obese patient.

PMID- 28739614
TI  - Apical ballooning (takotsubo) syndrome with concurrent ST-segment elevation
      myocardial infarction.
AB  - We present the case of a 61-year-old woman admitted with chest pain and an ECG
      demonstrating ST-segment elevation in the lateral leads. Emergency coronary
      angiography demonstrated an occluded obtuse marginal branch. Percutaneous
      intervention was unsuccessful as the lesion could not be crossed with a wire.
      Left ventriculography and transthoracic echocardiography demonstrated hypokinesis
      of the entire apex but preserved contractility of the basal segments, consistent
      with a diagnosis of apical ballooning syndrome (ABS). Cardiac MRI demonstrated
      myocardial oedema in all mid to apical segments, with a left ventricular ejection
      fraction (LVEF) of 38%. Repeat study at 5 months demonstrated an infarct in the
      distribution of the occluded artery with late gadolinium enhancement, consistent
      with a diagnosis of a lateral wall myocardial infarction and an improvement in
      the LVEF to 51%. The case illustrates the novel observation that ABS and acute
      myocardial infarction may rarely occur simultaneously.

PMID- 28739615
TI  - Primary bilateral adrenal nodular disease with Cushing's syndrome: varying
      aetiology.
AB  - Primary adrenal disorders contribute 20%a?"30% of patients with endogenous
      Cushing's syndrome. Most of the primary adrenal diseases are unilateral and
      include adenoma and adrenocortical carcinoma, whereas bilateral adrenal lesions
      are uncommon and include primary pigmented nodular adrenocortical disease,
      primary bilateral macronodular adrenocortical hyperplasia, isolated micronodular
      adrenocortical disease, bilateral adenomas or carcinomas, and rarely pituitary
      adrenocorticotropic hormone-dependent adrenal nodular disease. Cyclic adenosine
      monophosphate-dependent protein kinase A signalling is the major activator of
      cortisol secretion in primary adrenal nodular disorders. We report two cases of
      bilateral adrenal nodular disease with endogenous Cushing's syndrome, including
      one each of primary pigmented nodular adrenocortical disease and primary
      bilateral macronodular adrenocortical hyperplasia.

PMID- 28739616
TI  - Awakening with amantadine from a persistent vegetative state after subarachnoid
      haemorrhage.
AB  - We report the case of a 36-year-old woman with a subarachnoid haemorrhage (SAH)
      caused by a rupture of a right-sided middle cerebral artery aneurysm and
      subsequent malignant infarction of the right hemisphere leading to a persistent
      vegetative state and severe spastic tetraparesis with recurrent myocloni. Nine
      months after disease onset, the patient was transferred to our department for
      diagnostic and therapeutic re-evaluation. The poor clinical condition could not
      be explained by the brain lesion caused by the SAH or infarction. Moreover,
      glucose metabolism was normal in brain regions not affected by SAH and infarction
      as shown by positron emission tomography with 18F-fluorodeoxyglucose. We
      terminated baclofen and reduced antiepileptics known to impair vigilance and
      cognitive functions. However, only after starting amantadine treatment we
      observed a stunning awakening of the patient fully orientated within days. Our
      findings warrant trials to investigate amantadine in the treatment of
      unresponsive wakefulness syndromes due to acute central nervous system diseases.

PMID- 28739617
TI  - Paediatric chest wall trauma causing delayed presentation of ventricular
      arrhythmia.
AB  - This report describes a paediatric patient presenting with haemodynamically
      stable non-sustained ventricular tachycardia 1 day after minor blunt chest
      trauma. Initial laboratory studies, chest X-ray and echocardiography were normal;
      however, cardiac MRI revealed precordial haematoma, myocardial contusion and
      small pericardial effusion. Throughout her hospital course, she remained
      asymptomatic aside from frequent couplets and triplets of premature ventricular
      contractions. Ectopy was controlled with oral verapamil. This case highlights how
      significant cardiac injury may be missed with standard diagnostic algorithms.

PMID- 28739618
TI  - Atypical presentation of Parsonage-Turner syndrome confounded by surgical rotator
      cuff injury.
AB  - Parsonage-Turner syndrome (PTS) is a rare neuropathy that commonly presents as
      unexpected severe shoulder and arm pain that eventually subsides while weakness
      or paralysis ensues. During exceptions to this classic presentation, confirming
      PTS can be challenging. Alternative causes of upper extremity pain may confound
      the diagnostic algorithm. Moreover, objective findings from necessary diagnostic
      tests depend on when those tests are performed. We present an atypical onset of
      PTS, whereby the initial presentation of severe neuropathic pain was preceded by
      mild shoulder pain that should decrease one's clinical suspicion for PTS. This
      milder pain coincided with the presence of a rotator cuff injury, whereby
      surgical intervention preceded impending paralysis and hindered postoperative
      rehabilitation. Physicians should be aware of the possibility of atypical
      presentations of PTS in hopes of avoiding either untimely surgery or delays in
      diagnosis.

PMID- 28739619
TI  - Q fever prosthetic joint infection.
AB  - Coxiella burnetii is the causative pathogen of the zoonotic infection Q fever.
      Most patients with Q fever experience a non-specific febrile illness, hepatitis
      or pneumonia. Q fever has recently been described as a cause of prosthetic joint
      septic arthritis, but remains very uncommonly reported. We present a case of Q
      fever prosthetic joint septic arthritis that has responded to a combination of
      two-stage surgical exchange and prolonged medical treatment with doxycycline and
      hydroxychloroquine.

PMID- 28739620
TI  - A rare case of fatal meningoencephalitis with septic thromboembolism due to
      otitis media: a forensic case and review of literature.

PMID- 28739621
TI  - Lipoma of superior vena cava: a rare occurrence.
AB  - Most benign primary cardiac tumours are myxomas; non-myxomatous tumours are less
      common but comprise a wide variety. Cardiac lipoma is a rare non-myxomatous
      variety. A 70-year-old Caucasian woman with right breast cancer status
      postpartial mastectomy underwent surveillance MRI of the breast and was found to
      have a possible right atrial (RA) mass. She also reported frequent headaches and
      palpitations. She underwent a transoesophageal echocardiogram which showed a
      2.6*1.6*1.6 cm echogenic mass at the superior vena cava (SVC) and RA junction.
      She was anticoagulated for a possible thrombus without resolution. Surgical
      excision was undertaken in view of ongoing symptoms and partial occlusion of the
      SVC. Intraoperatively, a 2-3 cm smoothly textured lobulated mass was found and
      histopathology showed adipose tissue consistent with lipoma. The postoperative
      course was uneventful, and the patient was discharged in stable condition.

PMID- 28739622
TI  - An unusual case of interstitial lung disease in a patient with cardiopulmonary
      syndrome as the initial presentation of Erdheim-Chester disease.
AB  - Erdheim-Chester disease (ECD) is a very rare disorder with only approximately 600
      cases reported in the literature. ECD has been recently reclassified as a
      histiocytic dendritic cell neoplasm. The clinical spectrum ranges from
      asymptomatic tissue accumulation of histiocytes to invasive tissue infiltration,
      which can cause fulminant multisystem failure. It typically presents with bone
      pain and constitutional symptoms. Extraosseous manifestations are not uncommon.
      ECD-associated interstitial lung disease has been described in 20%-35% of
      patients. Diagnosis is primarily by tissue biopsy and immunohistochemistry
      showing xanthogranulomas composed of foamy histiocytes that stain positive for
      CD68, CD14 and CD163 and negative for CD1a and langerin. We report a case of ECD
      in a young man with cardiopulmonary involvement who presented with haemoptysis
      and dyspnoea.

PMID- 28739623
TI  - Importance of temporal changes in myocardial strain in Takotsubo cardiomyopathy.
AB  - Strain imaging is a sensitive marker of myocardial dysfunction and may be
      underused in Takotsubo cardiomyopathy (TC). We present a case of biventricular TC
      in which early improvement in left ventricular longitudinal strain predated
      subsequent improvement in ejection fraction. Early temporal patterns of strain of
      the left and right ventricles have not previously been described in TC. Our case
      illustrates how strain can be a sensitive marker for myocardial dysfunction and
      recovery in TC. Increased use of strain in TC may have further implications on
      prognosis and management.

PMID- 28739624
TI  - Klippel-Trenaunay syndrome: diagnosis in a neonate.

PMID- 28739625
TI  - Trans-scaphoid perilunate fracture dislocation: 'notjust a scaphoid fracture'.

PMID- 28739626
TI  - Patient-reported outcome measures (PROMs): enhancing decision making and follow
      up.
AB  - A case presentation of patient undergoing elective total knee replacement.
      Patient-reported outcome measures prospectively collected electronically pre and
      postoperatively allowed real-time review, aiding follow-up and reducing the need
      for clinical, face-to-face follow-up.

PMID- 28739627
TI  - Reconstruction of urethra using appendix in a patient with cloacal malformation.
AB  - We report a case of 21-year-old young woman with congenital cloacal malformation.
      She was operated at the age of 1.5 years separating the rectum from common
      opening as a two-stage repair. She was incontinent in the earlier part of her
      life but she became continent to some extent later in early adulthood. She
      presented with urinary stress incontinence following delivery of dead fetus of 6
      months. She underwent multiple investigations revealing common opening of bladder
      neck and vagina. A multidisciplinary evaluation was done and she underwent
      closure of common channel and neourethra reconstruction using pedicled appendix.
      Patient was continent and voiding by herself on discharge.

PMID- 28739628
TI  - Angioscopic observation of an atherosclerotic coronary aneurysm without yellow
      plaque.

PMID- 28739629
TI  - Charting the Future of Cancer Health Disparities Research: A Position Statement
      from the American Association for Cancer Research, the American Cancer Society,
      the American Society of Clinical Oncology, and the National Cancer Institute.

PMID- 28739630
TI  - Psychosexual medicine, general practice, you and me.

PMID- 28739631
TI  - Uterine perforation by intrauterine devices: a 16-year review.
AB  - INTRODUCTION: One of the major concerns with the insertion of intrauterine
      devices is uterine perforation. Though uncommon, it can be debilitating and
      result in failure of the device. In this article we review uterine perforation
      with intrauterine contraception (IUC) in a community clinic in the UK over a 16
      year period. METHODS: We prospectively collected data on uterine perforations for
      the years 2000-2015, reviewed associated factors and calculated the annual rate
      of perforation, estimating if this lay within the expected range of normal
      variation using statistical process control (SPC) analysis. We analysed the rates
      of perforation in relation to the time from delivery and to breastfeeding.
      RESULTS: We identified 30 uterine perforations in 22 795 IUC insertions over the
      16 years of observation, with an annual rate ranging from 0 to 4.3 per 1000
      insertions, and a mean annual rate of 1.3 per 1000 insertions (95% CI 0.9 to
      1.9), which remain within the SPC limits. Twenty-eight of the perforations were
      in parous women, 87% of whom were within 18 weeks of delivery, peaking at 13
      weeks postpartum. Twenty of these were in breastfeeding women. In 3/28 cases for
      which we have outcome data the device was adherent to or had perforated either
      the bladder or bowel. CONCLUSION: Our perforation rate is consistent with other
      studies. Most of our perforations were within 18 weeks of childbirth, earlier
      than in a recent major study. We cannot tell from our data if there is a true
      peak in perforations 3 months postpartum as that may be a time when a high
      proportion of insertions are done.

PMID- 28739632
TI  - Therapeutic potential of mesenchymal stem cells for diabetes.
AB  - Mesenchymal stem cells (MSCs) are self-renewing multipotent cells that have the
      capacity to secrete multiple biologic factors that can restore and repair injured
      tissues. Preclinical and clinical evidence have substantiated the therapeutic
      benefit of MSCs in various medical conditions. Currently, MSCs are the most
      commonly used cell-based therapy in clinical trials because of their regenerative
      effects, ease of isolation and low immunogenicity. Experimental and clinical
      studies have provided promising results using MSCs to treat diabetes. This review
      will summarize the role of MSCs on tissue repair, provide emerging strategies to
      improve MSC function and describe how these processes translate to clinical
      treatments for diabetes.

PMID- 28739633
TI  - Claudin-8d is a cortisol-responsive barrier protein in the gill epithelium of
      trout.
AB  - The influence of claudin (Cldn) 8 tight junction (TJ) proteins on cortisol
      mediated alterations in gill epithelium permeability was examined using a primary
      cultured trout gill epithelium model. Genes encoding three Cldn-8 proteins (cldn
      8b, -8c and -8d) have been identified in trout and all are expressed in the model
      gill epithelium. Cortisol treatment 'tightened' the gill epithelium, as indicated
      by increased transepithelial resistance (TER) and reduced paracellular
      [3H]polyethylene glycol (MW 400 Da; PEG-400) flux. This occurred in association
      with elevated cldn-8d mRNA abundance, but no alterations in cldn-8b and -8c mRNA
      abundance were observed. Transcriptional knockdown (KD) of cldn-8d inhibited a
      cortisol-induced increase in Cldn-8d abundance and reduced the 'epithelium
      tightening' effect of cortisol in association with increased paracellular PEG-400
      flux. Under simulated in vivo conditions (i.e. apical freshwater), cldn-8d KD
      hindered a cortisol-mediated reduction in basolateral to apical Na+ and Cl- flux
      (i.e. reduced the ability of cortisol to mitigate ion loss). However, cldn-8d KD
      did not abolish the tightening effect of cortisol on the gill epithelium. This is
      likely due, in part, to the effect of cortisol on genes encoding other TJ
      proteins, which in some cases appeared to exhibit a compensatory response. Data
      support the idea that Cldn-8d is a barrier protein of the gill epithelium TJ that
      contributes significantly to corticosteroid-mediated alterations in gill
      epithelium permeability.

PMID- 28739634
TI  - Management of severe hypertension in the newborn.
AB  - Blood pressure is considered a vital sign, as values too low or too high can be
      related with serious morbidity and mortality. In neonates, normal blood pressure
      values undergo rapid changes, especially in premature infants, making the
      recognition of abnormal blood pressures more challenging. Severe hypertension can
      occur in neonates and infants and is a medical emergency, often manifesting with
      congestive heart failure or other life-threatening complications. The cause or
      risk factors for the hypertension can usually be identified and may guide
      management. Most classes of antihypertensive medications have been used in the
      neonatal population. For severe hypertension, intravenous short-acting
      medications are preferred for a controlled reduction of blood pressure. In this
      article, we focus on identification, aetiology and management of severe
      hypertension in the newborn.

PMID- 28739635
TI  - Investigating early developmental impairment: what's the cost?

PMID- 28739636
TI  - Immunoassay for human serum erythroferrone.
AB  - Erythroferrone (ERFE) is a glycoprotein hormone secreted by erythroblasts in
      response to stimulation by erythropoietin (EPO). We previously demonstrated that
      ERFE messenger RNA expression and serum protein concentration increase in mice
      subjected to hemorrhage or EPO therapy, that ERFE acts on hepatocytes to suppress
      hepcidin, and that the resulting decrease in hepcidin augments iron delivery for
      intensified erythropoiesis. We also showed that ERFE contributes to pathological
      hepcidin suppression and iron overload in mice with nontransfused beta
      thalassemia. We now report the development and technical validation of a rabbit
      monoclonal antibody-based sandwich immunoassay for human ERFE. We use this assay
      to show that blood loss or EPO administration increases serum ERFE concentrations
      in humans, and that patients with both nontransfused and transfused beta
      thalassemia have very high serum ERFE levels, which decrease after blood
      transfusion. The assay should be useful for human studies of normal and
      disordered erythropoiesis and its effect on iron homeostasis.

PMID- 28739637
TI  - Distributive justice and the harm to medical professionals fighting epidemics.
AB  - The exposure of doctors, nurses and other medical professionals to risks in the
      context of epidemics is significant. While traditional medical ethics offers the
      thought that these dangers may limit the extent to which a duty to care is
      applicable in such situations, it has less to say about what we might owe to
      medical professionals who are disadvantaged in these contexts. Luck
      egalitarianism, a responsibility-sensitive theory of distributive justice,
      appears to fare particularly badly in that regard. If we want to maintain that
      medical professionals are responsible for their decisions to help, cure and care
      for the vulnerable, luck egalitarianism seems to imply that their claim of
      justice to medical attention in case of infection is weak or non-existent. The
      article demonstrates how a recent interpretation of luck egalitarianism offers a
      solution to this problem. Redefining luck egalitarianism as concerned with
      responsibility for creating disadvantages, rather than for incurring disadvantage
      as such, makes it possible to maintain that medical professionals are responsible
      for their choices and that those infected because of their choice to help fight
      epidemics have a full claim of justice to medical attention.

PMID- 28739638
TI  - Undue inducement, or unfair exclusion: considering a case study of pregnancy in
      an HIV prevention trial.
AB  - In their recent paper'Undue inducement: a case study in CAPRISA 008', Mngadi et
      al conclude that a participant in an HIV prevention study who deliberately
      concealed her pregnancy was not 'unduly induced' to participate by the offer of
      an experimental product. This paper argues that while the authors' conclusion is
      sound, the framing of this case study is consistent with the preoccupation in
      research ethics with the concept of undue inducement, coupled with a highly risk
      averse attitude to pregnancy (regardless of whether those risks may be willingly
      assumed by pregnant women themselves). We suggest that the critical research
      ethics question raised by Mngadi et al's case study is not 'undue inducement',
      but the exclusion of pregnant women from research studies where the risks are
      acceptable to the potential participant, and benefits likely. We also suggest
      that current regulatory paradigms regarding pregnancy are both overly
      paternalistic and value the fetus over the mother. In order to ensure timely
      provision of new HIV prevention agents, we argue that there is a need for
      expeditious testing of proven effective agents in pregnancy, with due
      consideration given to situations where preliminary efficacy data exist but fall
      short of licensure standards. This requires a paradigm shift from researchers,
      funders, regulators and ethical review bodies towards practices that critically
      examine the legitimacy of the exclusion of pregnant women on a study-by-study
      basis.

PMID- 28739639
TI  - Advances in neuroscience imply that harmful experiments in dogs are unethical.
AB  - Functional MRI (fMRI) of fully awake and unrestrained dog 'volunteers' has been
      proven an effective tool to understand the neural circuitry and functioning of
      the canine brain. Although every dog owner would vouch that dogs are perceptive,
      cognitive, intuitive and capable of positive emotions/empathy, as indeed
      substantiated by ethological studies for some time, neurological investigations
      now corroborate this. These studies show that there exists a striking similarity
      between dogs and humans in the functioning of the caudate nucleus (associated
      with pleasure and emotion), and dogs experience positive emotions, empathic-like
      responses and demonstrate human bonding which, some scientists claim, may be at
      least comparable with human children. There exists an area analogous to the
      'voice area' in the canine brain, enabling dogs to comprehend and respond to
      emotional cues/valence in human voices, and evidence of a region in the temporal
      cortex of dogs involved in the processing of faces, as also observed in humans
      and monkeys. We therefore contend that using dogs in invasive and/or harmful
      research, and toxicity testing, cannot be ethically justifiable.

PMID- 28739640
TI  - EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by
      regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS.
AB  - Obesity, which is caused by an energy imbalance between calorie intake and
      consumption, has become a major international health burden. Obesity increases
      the risk of insulin resistance and age-related cognitive decline, accompanied by
      peripheral inflammation. (-)-Epigallocatechin-3-gallate (EGCG), the major
      polyphenol in green tea, possesses antioxidant, anti-inflammatory, and
      cardioprotective activities; however, few reports have focused on its potential
      effect on cognitive disorders. In this study, our goal was to investigate the
      protective effects of EGCG treatment on insulin resistance and memory impairment
      induced by a high-fat and high-fructose diet (HFFD). We randomly assigned 3-mo
      old C57BL/6J mice to 3 groups with different diets: control group, HFFD group,
      and HFFD plus EGCG group. Memory loss was assessed by using the Morris water maze
      test, during which EGCG was observed to prevent HFFD-elicited memory impairment
      and neuronal loss. Consistent with these results, EGCG attenuated HFFD-induced
      neuronal damage. Of note, EGCG significantly ameliorated insulin resistance and
      cognitive disorder by up-regulating the insulin receptor substrate-1 (IRS-1)/AKT
      and ERK/cAMP response element binding protein (CREB)/brain-derived neurotrophic
      factor (BDNF) signaling pathways. Long-term HFFD-triggered neuroinflammation was
      restored by EGCG supplementation by inhibiting the MAPK and NF-kappaB pathways,
      as well as the expression of inflammatory mediators, such as TNF-alpha. EGCG also
      reversed high glucose and glucosamine-induced insulin resistance in SH-SY5Y
      neuronal cells by improving the oxidized cellular status and mitochondrial
      function. To our knowledge, this study is the first to provide compelling
      evidence that the nutritional compound EGCG has the potential to ameliorate HFFD
      triggered learning and memory loss.-Mi, Y., Qi, G., Fan, R., Qiao, Q., Sun, Y.,
      Gao, Y., Liu, X. EGCG ameliorates high-fat- and high-fructose-induced cognitive
      defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the
      CNS.

PMID- 28739641
TI  - Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced
      osteoclastogenesis.
AB  - Osteoporosis is a metabolic bone disease characterized by decreased bone density
      and strength due to excessive loss of bone protein and mineral content. The
      imbalance between osteogenesis by osteoblasts and osteoclastogenesis by
      osteoclasts contributes to the pathogenesis of postmenopausal osteoporosis.
      Estrogen withdrawal leads to increased levels of proinflammatory cytokines.
      Overactivated osteoclasts by inflammation play a vital role in the imbalance.
      Matrine is an alkaloid found in plants from the Sophora genus with various
      pharmacological effects, including anti-inflammatory activity. Here we
      demonstrate that matrine significantly prevented ovariectomy-induced bone loss
      and inhibited osteoclastogenesis in vivo with decreased serum levels of TRAcp5b,
      TNF-alpha, and IL-6. In vitro matrine significantly inhibited osteoclast
      differentiation induced by receptor activator for NF-kappaB ligand (RANKL) and M
      CSF in bone marrow monocytes and RAW264.7 cells as demonstrated by tartrate
      resistant acid phosphatase (TRAP) staining and actin-ring formation as well as
      bone resorption through pit formation assays. For molecular mechanisms, matrine
      abrogated RANKL-induced activation of NF-kappaB, AKT, and MAPK pathways and
      suppressed osteoclastogenesis-related marker expression, including matrix
      metalloproteinase 9, NFATc1, TRAP, C-Src, and cathepsin K. Our study demonstrates
      that matrine inhibits osteoclastogenesis through modulation of multiple pathways
      and that matrine is a promising agent in the treatment of osteoclast-related
      diseases such as osteoporosis.-Chen, X., Zhi, X., Pan, P., Cui, J., Cao, L.,
      Weng, W., Zhou, Q., Wang, L., Zhai, X. Zhao, Q., Hu, H., Huang, B., Su, J.
      Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced
      osteoclastogenesis.

PMID- 28739642
TI  - Animal models of ocular angiogenesis: from development to pathologies.
AB  - Pathological angiogenesis in the eye is an important feature in the
      pathophysiology of many vision-threatening diseases, including retinopathy of
      prematurity, diabetic retinopathy, and age-related macular degeneration, as well
      as corneal diseases with abnormal angiogenesis. Development of reproducible and
      reliable animal models of ocular angiogenesis has advanced our understanding of
      both the normal development and the pathobiology of ocular neovascularization.
      These models have also proven to be valuable experimental tools with which to
      easily evaluate potential antiangiogenic therapies beyond eye research. This
      review summarizes the current available animal models of ocular angiogenesis.
      Models of retinal and choroidal angiogenesis, including oxygen-induced
      retinopathy, laser-induced choroidal neovascularization, and transgenic mouse
      models with deficient or spontaneous retinal/choroidal neovascularization, as
      well as models with induced corneal angiogenesis, are widely used to investigate
      the molecular and cellular basis of angiogenic mechanisms. Theoretical concepts
      and experimental protocols of these models are outlined, as well as their
      advantages and potential limitations, which may help researchers choose the most
      suitable models for their investigative work.-Liu, C.-H., Wang, Z., Sun, Y.,
      Chen, J. Animal models of ocular angiogenesis: from development to pathologies.

PMID- 28739643
TI  - Histone methyltransferase Dot1L is a coactivator for thyroid hormone receptor
      during Xenopus development.
AB  - Histone modifications are associated with transcriptional regulation by diverse
      transcription factors. Genome-wide correlation studies have revealed that histone
      activation marks and repression marks are associated with activated and repressed
      gene expression, respectively. Among the histone activation marks is histone H3
      K79 methylation, which is carried out by only a single methyltransferase,
      disruptor of telomeric silencing-1-like (DOT1L). We have been studying thyroid
      hormone (T3)-dependent amphibian metamorphosis in two highly related species, the
      pseudo-tetraploid Xenopus laevis and diploid Xenopus tropicalis, as a model for
      postembryonic development, a period around birth in mammals that is difficult to
      study. We previously showed that H3K79 methylation levels are induced at T3
      target genes during natural and T3-induced metamorphosis and that Dot1L is itself
      a T3 target gene. These suggest that T3 induces Dot1L expression, and Dot1L in
      turn functions as a T3 receptor (TR) coactivator to promote vertebrate
      development. We show here that in cotransfection studies or in the reconstituted
      frog oocyte in vivo transcription system, overexpression of Dot1L enhances gene
      activation by TR in the presence of T3. Furthermore, making use of the ability to
      carry out transgenesis in X. laevis and gene knockdown in X. tropicalis, we
      demonstrate that endogenous Dot1L is critical for T3-induced activation of
      endogenous TR target genes while transgenic Dot1L enhances endogenous TR function
      in premetamorphic tadpoles in the presence of T3. Our studies thus for the first
      time provide complementary gain- and loss-of functional evidence in vivo for a
      cofactor, Dot1L, in gene activation by TR during vertebrate development.-Wen, L.,
      Fu, L., Shi, Y.-B. Histone methyltransferase Dot1L is a coactivator for thyroid
      hormone receptor during Xenopus development.

PMID- 28739644
TI  - NRT1.5/NPF7.3 Functions as a Proton-Coupled H+/K+ Antiporter for K+ Loading into
      the Xylem in Arabidopsis.
AB  - Potassium and nitrogen are essential macronutrients for plant growth and have a
      positive impact on crop yield. Previous studies have indicated that the
      absorption and translocation of K+ and NO3- are correlated with each other in
      plants; however, the molecular mechanism that coordinates K+ and NO3- transport
      remains unknown. In this study, using a forward genetic approach, we isolated a
      low-K+-sensitive Arabidopsis thaliana mutant, lks2, that showed a leaf chlorosis
      phenotype under low-K+ conditions. LKS2 encodes the transporter NRT1.5/NPF7.3, a
      member of the NRT1/PTR (Nitrate Transporter 1/Peptide Transporter) family. The
      lks2/nrt1.5 mutants exhibit a remarkable defect in both K+ and NO3- translocation
      from root to shoot, especially under low-K+ conditions. This study demonstrates
      that LKS2 (NRT1.5) functions as a proton-coupled H+/K+ antiporter. Proton
      gradient can promote NRT1.5-mediated K+ release out of root parenchyma cells and
      facilitate K+ loading into the xylem. This study reveals that NRT1.5 plays a
      crucial role in K+ translocation from root to shoot and is also involved in the
      coordination of K+/NO3- distribution in plants.

PMID- 28739645
TI  - Repeatability of vessel density measurements of optical coherence tomography
      angiography in normal and glaucoma eyes.
AB  - AIMS: To compare the intrasession repeatability of peripapillary and macular
      vessel density measurements of optical coherence tomography angiography (OCTA) in
      normal and glaucoma eyes, and to evaluate the effect of signal strength of OCTA
      scans on the repeatability. METHODS: In a cross-sectional study, three optic
      nerve head scans each of 65 eyes (30 normal, 35 glaucoma eyes) and three macular
      scans each of 69 eyes (35 normal, 34 glaucoma eyes) acquired in the same session
      with OCTA were analysed. Repeatability was assessed using within-subject
      coefficient of repeatability (CRw) and variation (CVw). Effect of signal strength
      index (SSI) on repeatability was evaluated with repeated-measures mixed-effects
      models. RESULTS: CRw (%) and CVw (%) of peripapillary measurements in normal eyes
      ranged between 3.3 and 7.0, and 2.5 and 4.4 respectively, and that in glaucoma
      eyes between 3.5 and 7.1, and 2.6 and 6.6. For the macular, these measurements
      ranged between 4.1 and 6.0, and 3.3 and 4.7 in normal eyes and 4.3 and 6.9, and
      3.7 and 5.6 in glaucoma eyes. Repeatability estimates of most measurements were
      similar in normal and glaucoma eyes. Vessel densities of both peripapillary and
      macular regions significantly increased with increase in SSI of repeat scans
      (coefficients ranging from 0.15 to 0.38, p<0.01 for all associations).
      CONCLUSIONS: Repeatability estimates of OCTA measured peripapillary and macular
      vessel densities were similar in normal eyes and eyes with glaucoma. SSI values
      of the scans had a significant effect on the repeatability of OCTA with the
      vessel density values increasing in scans with higher SSI values.

PMID- 28739646
TI  - KOH mount as an aid in the management of infectious keratitis at secondary eye
      care centre.
AB  - AIMS: To report the clinical outcome of infectious keratitis managed after doing
      10% KOH mount of corneal smears and reporting done by an ophthalmologist in the
      secondary eye care centre in South India. METHODS: 103 consecutive cases of
      microbial keratitis were studied. Inclusion criteria were presence of corneal
      infiltrate on slit lamp biomicroscopy. An ophthalmologist carried out
      microbiological evaluation of 10% KOH mount of corneal scrapings. No cultures
      were done at secondary centres. Antifungal therapy with 5% Natamycin was
      initiated when 10% KOH mount was positive for fungal filaments. Else, the
      patients were started on combined topical ciprofloxacin (0.3%) and fortified
      cefazolin (5%). RESULTS: 41/103 (39.8%) smears were positive for fungus and 62
      (60.2%) were negative. 89 out of 103 patients (86.40%) healed with scarring at an
      average of 2.95+/-1.58 weeks. Healing was noted in 39/41 (95.12%) of patients at
      an average of 3.06+/-1.19 weeks in patients with KOH smear positive keratitis.
      80.64% (50/62) healed with scarring at an average period of 2.86+/-1.86 weeks in
      KOH mount negative keratitis. CONCLUSIONS: Initial smear examination of KOH mount
      by an ophthalmologist helped in diagnosis of infectious keratitis caused by fungi
      and its management and 95.12% of KOH positive patients healed with scarring.
      Reading of KOH mount by an ophthalmologist helped in initiation of specific
      therapy with improved clinical outcome.

PMID- 28739647
TI  - Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart
      Failure.
AB  - Understanding the tubular location of diuretic resistance (DR) in heart failure
      (HF) is critical to developing targeted treatment strategies. Rodents chronically
      administered loop diuretics develop DR due to compensatory distal tubular sodium
      reabsorption, but whether this translates to human DR is unknown. We studied
      consecutive patients with HF (n=128) receiving treatment with loop diuretics at
      the Yale Transitional Care Center. We measured the fractional excretion of
      lithium (FELi), the gold standard for in vivo assessment of proximal tubular and
      loop of Henle sodium handling, to assess sodium exit after loop diuretic
      administration and FENa to assess the net sodium excreted into the urine. The
      mean+/-SD prediuretic FELi was 16.2%+/-9.5%, similar to that in a control cohort
      without HF not receiving diuretics (n=52; 16.6%+/-9.2%; P=0.82). Administration
      of a median of 160 (interquartile range, 40-270) mg intravenous furosemide
      equivalents increased FELi by 12.6%+/-10.8% (P<0.001) but increased FENa by only
      4.8%+/-3.3%. Thus, only 34% (interquartile range, 15.6%-75.7%) of the estimated
      diuretic-induced sodium release did not undergo distal reabsorption. After
      controlling for urine diuretic levels, the increase in FELi explained only 6.4%
      of the increase in FENa (P=0.002). These data suggest that administration of high
      dose loop diuretics to patients with HF yields meaningful increases in sodium
      exit from the proximal tubule/loop of Henle. However, little of this sodium seems
      to reach the urine, consistent with findings from animal models that indicate
      that distal tubular compensatory sodium reabsorption is a primary driver of DR.

PMID- 28739648
TI  - Hepatocyte Nuclear Factor-1beta Controls Mitochondrial Respiration in Renal
      Tubular Cells.
AB  - AKI is a frequent condition that involves renal microcirculation impairment,
      infiltration of inflammatory cells with local production of proinflammatory
      cytokines, and subsequent epithelial disorders and mitochondrial dysfunction.
      Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A),
      a coactivator of the transcription factor PPAR-gamma that controls mitochondrial
      biogenesis and function, has a pivotal role in the early dysfunction of the
      proximal tubule and the subsequent renal repair. Here, we evaluated the potential
      role of hepatocyte nuclear factor-1beta (HNF-1beta) in regulating PPARGC1A
      expression in AKI. In mice, endotoxin injection to induce AKI also induced early
      and transient inflammation and PPARGC1A inhibition, which overlapped with
      downregulation of the HNF-1beta transcriptional network. In vitro, exposure of
      proximal tubule cells to the inflammatory cytokines IFN-gamma and TNF-alpha led
      to inhibition of HNF-1beta transcriptional activity. Moreover, inhibition of HNF
      1beta significantly reduced PPARGC1A expression and altered mitochondrial
      morphology and respiration in proximal tubule cells. Chromatin
      immunoprecipitation assays and PCR analysis confirmed HNF-1beta binding to the
      Ppargc1a promoter in mouse kidneys. We also demonstrated downregulation of renal
      PPARGC1A expression in a patient with an HNF1B germinal mutation. Thus, we
      propose that HNF-1beta links extracellular inflammatory signals to mitochondrial
      dysfunction during AKI partly via PPARGC1A signaling. Our findings further
      strengthen the view of HNF1B-related nephropathy as a mitochondrial disorder in
      adulthood.

PMID- 28739649
TI  - Persistent Microscopic Hematuria as a Risk Factor for Progression of IgA
      Nephropathy: New Floodlight on a Nearly Forgotten Biomarker.

PMID- 28739650
TI  - Lysophosphatidic Acid Receptor Antagonism Protects against Diabetic Nephropathy
      in a Type 2 Diabetic Model.
AB  - Lysophosphatidic acid (LPA) functions through activation of LPA receptors
      (LPARs). LPA-LPAR signaling has been implicated in development of fibrosis.
      However, the role of LPA-LPAR signaling in development of diabetic nephropathy
      (DN) has not been studied. We examined whether BMS002, a novel dual LPAR1 and
      LPAR3 antagonist, affects development of DN in endothelial nitric oxide synthase
      knockout db/db mice. Treatment of these mice with BMS002 from 8 to 20 weeks of
      age led to a significant reduction in albuminuria, similar to that observed with
      renin-angiotensin system inhibition (losartan plus enalapril). LPAR inhibition
      also prevented the decline in GFR observed in vehicle-treated mice, such that GFR
      at week 20 differed significantly between vehicle and LPAR inhibitor groups
      (P<0.05). LPAR inhibition also reduced histologic glomerular injury; decreased
      the expression of profibrotic and fibrotic components, including fibronectin,
      alpha-smooth muscle actin, connective tissue growth factor, collagen I, and TGF
      beta; and reduced renal macrophage infiltration and oxidative stress. Notably,
      LPAR inhibition slowed podocyte loss (podocytes per glomerulus +/-SEM at 8 weeks:
      667+/-40, n=4; at 20 weeks: 364+/-18 with vehicle, n=7, and 536+/-12 with LPAR
      inhibition, n=7; P<0.001 versus vehicle). Finally, LPAR inhibition minimized the
      production of 4-hydroxynonenal (4-HNE), a marker of oxidative stress, in
      podocytes and increased the phosphorylation of AKT2, an indicator of AKT2
      activity, in kidneys. Thus, the LPAR antagonist BMS002 protects against GFR
      decline and attenuates development of DN through multiple mechanisms. LPAR
      antagonism might provide complementary beneficial effects to renin-angiotensin
      system inhibition to slow progression of DN.

PMID- 28739651
TI  - Improving Asthma Care by Building Statewide Quality Improvement Infrastructure.
AB  - BACKGROUND AND OBJECTIVES: Pediatric medical professionals have an increasing
      desire for quality improvement (QI) methods that produce sustainable changes in
      health care delivery. Previous reports have described QI in single settings or
      single coordinating entities that work with multiple sites. The objectives of
      this project are (1) to improve care for children with asthma across multiple
      practice settings and (2) to develop state-level expertise to support QI projects
      across entities in multiple states. METHODS: Using a multiwave approach, the
      Chapter Quality Network of the American Academy of Pediatrics implemented
      statewide learning collaboratives in several states. For each cycle, a national
      leadership team coached multiple American Academy of Pediatrics chapter
      leadership teams, which, in turn, coached individual pediatric practices through
      2 nested learning collaboratives. State chapters received data and reporting
      tools and a curriculum fostering QI learning and support change at the practice
      level. Practices implemented an asthma assessment tool and registry, analyzed
      work flows, and implemented self-management tools in plan-do-study-act cycles.
      Sixteen process and outcome measures, including optimal asthma care, were
      collected and analyzed by using run charts on a monthly dashboard. Chapter
      leaders provided feedback on sustainable QI change through surveys and
      interviews. RESULTS: Optimal asthma care improved from 42% to 81% across the 4
      waves. The percentage of patients rated by physicians as well controlled rose
      from 59% to 74%. CONCLUSIONS: Asthma care can be improved by supporting practice
      change through statewide QI learning collaboratives.

PMID- 28739652
TI  - In-Hospital Quality-of-Care Measures for Pediatric Sepsis Syndrome.
AB  - BACKGROUND AND OBJECTIVES: Sepsis syndrome, comprising sepsis, severe sepsis, and
      septic shock, is a leading cause of child mortality and morbidity, for which the
      delivery of time-sensitive care leads to improved survival. We aimed to describe
      the development and testing of quality measures for in-hospital care of pediatric
      sepsis syndrome. METHODS: Seven measures of quality of care for children
      hospitalized with sepsis syndrome were developed by using an iterative process
      including literature review, development of concepts and candidate measures, and
      selection of measures for feasibility and importance by 2 panels of experts. The
      measures were tested for reliability and validity among children 0 to 18 years of
      age hospitalized with sepsis syndrome from January 1, 2012, to June 30, 2013.
      RESULTS: Of 27 hospitals, 59% had no protocol for the identification and
      treatment of pediatric sepsis syndrome. Blood culture was performed in only 70%
      of patients with pediatric sepsis syndrome. Antibiotics were administered within
      1 hour of diagnosis in 70% of patients with pediatric severe sepsis or septic
      shock, and timely fluid resuscitation was performed in 50% of patients with
      severe sepsis or septic shock. Documentation of heart rate during fluid
      resuscitation of children with severe sepsis or septic shock was observed in 18%
      of cases. Two measures could not be rigorously tested for validity and
      reliability given the rarity of septic shock and were deemed infeasible.
      CONCLUSIONS: This multisite study to develop and validate measures of the quality
      of hospital care of children with sepsis syndrome highlights the existence of
      important gaps in delivery of care.

PMID- 28739654
TI  - Operating Procedures for Pediatric Telehealth.

PMID- 28739653
TI  - The Metabolic Syndrome in Children and Adolescents: Shifting the Focus to
      Cardiometabolic Risk Factor Clustering.
AB  - Metabolic syndrome (MetS) was developed by the National Cholesterol Education
      Program Adult Treatment Panel III, identifying adults with at least 3 of 5
      cardiometabolic risk factors (hyperglycemia, increased central adiposity,
      elevated triglycerides, decreased high-density lipoprotein cholesterol, and
      elevated blood pressure) who are at increased risk of diabetes and cardiovascular
      disease. The constellation of MetS component risk factors has a shared
      pathophysiology and many common treatment approaches grounded in lifestyle
      modification. Several attempts have been made to define MetS in the pediatric
      population. However, in children, the construct is difficult to define and has
      unclear implications for clinical care. In this Clinical Report, we focus on the
      importance of screening for and treating the individual risk factor components of
      MetS. Focusing attention on children with cardiometabolic risk factor clustering
      is emphasized over the need to define a pediatric MetS.

PMID- 28739655
TI  - Critical Issues in Food Allergy: A National Academies Consensus Report.
AB  - The National Academies of Sciences, Engineering, and Medicine convened an expert,
      ad hoc committee to examine critical issues related to food allergy. The authors
      of the resulting report, "Finding a Path to Safety in Food Allergy: Assessment of
      the Global Burden, Causes, Prevention, Management, and Public Policy," evaluated
      the scientific evidence on the prevalence, diagnosis, prevention, and management
      of food allergy and made recommendations to bring about a safe environment for
      those affected. The committee recommended approaches to monitor prevalence,
      explore risk factors, improve diagnosis, and provide evidence-based health care.
      Regarding diagnostics, emphasis was placed on utilizing allergy tests judiciously
      in the context of the medical history because positive test results are not, in
      isolation, diagnostic. Evidence-based prevention strategies were advised (for
      example, a strategy to prevent peanut allergy through early dietary
      introduction). The report encourages improved education of stakeholders for
      recognizing and managing as well as preventing allergic reactions, including an
      emphasis on using intramuscular epinephrine promptly to treat anaphylaxis. The
      report recommends improved food allergen labeling and evaluation of the need for
      epinephrine autoinjectors with a dosage appropriate for infants. The committee
      recommended policies and guidelines to prevent and treat food allergic reactions
      in a various settings and suggested research priorities to address key questions
      about diagnostics, mechanisms, risk determinants, and management. Identifying
      safe and effective therapies is the ultimate goal. This article summarizes the
      key findings from the report and emphasizes recommendations for actions that are
      applicable to pediatricians and to the American Academy of Pediatrics.

PMID- 28739656
TI  - Guiding Principles for Team-Based Pediatric Care.
AB  - The American Academy of Pediatrics (AAP) recognizes that children's unique and
      ever-changing needs depend on a variety of support systems. Key components of
      effective support systems address the needs of the child and family in the
      context of their home and community and are dynamic so that they reflect,
      monitor, and respond to changes as the needs of the child and family change. The
      AAP believes that team-based care involving medical providers and community
      partners (eg, teachers and state agencies) is a crucial and necessary component
      of providing high-quality care to children and their families. Team-based care
      builds on the foundation of the medical home by reaching out to a potentially
      broad array of participants in the life of a child and incorporating them into
      the care provided. Importantly, the AAP believes that a high-functioning team
      includes children and their families as essential partners. The overall goal of
      team-based care is to enhance communication and cooperation among the varied
      medical, social, and educational partners in a child's life to better meet the
      global needs of children and their families, helping them to achieve their best
      potential. In support of the team-based approach, the AAP urges stakeholders to
      invest in infrastructure, education, and privacy-secured technology to meet the
      needs of children. This statement includes limited specific examples of potential
      team members, including health care providers and community partners, that are
      meant to be illustrative and in no way represent a complete or comprehensive
      listing of all team members who may be of importance for a specific child and
      family.

PMID- 28739657
TI  - Parental Management of Discharge Instructions: A Systematic Review.
AB  - CONTEXT: Parents often manage complex instructions when their children are
      discharged from the inpatient setting or emergency department (ED);
      misunderstanding instructions can put children at risk for adverse outcomes.
      Parents' ability to manage discharge instructions has not been examined before in
      a systematic review. OBJECTIVE: To perform a systematic review of the literature
      related to parental management (knowledge and execution) of inpatient and ED
      discharge instructions. DATA SOURCES: We consulted PubMed/Medline, Embase,
      Cumulative Index to Nursing and Allied Health Literature, and Cochrane CENTRAL
      (from database inception to January 1, 2017). STUDY SELECTION: We selected
      experimental or observational studies in the inpatient or ED settings in which
      parental knowledge or execution of discharge instructions were evaluated. DATA
      EXTRACTION: Two authors independently screened potential studies for inclusion
      and extracted data from eligible articles by using a structured form. RESULTS:
      Sixty-four studies met inclusion criteria; most (n = 48) were ED studies.
      Medication dosing and adherence errors were common; knowledge of medication side
      effects was understudied (n = 1). Parents frequently missed follow-up
      appointments and misunderstood return precaution instructions. Few researchers
      conducted studies that assessed management of instructions related to diagnosis
      (n = 3), restrictions (n = 2), or equipment (n = 1). Complex discharge plans (eg,
      multiple medicines or appointments), limited English proficiency, and public or
      no insurance were associated with errors. Few researchers conducted studies that
      evaluated the role of parent health literacy (ED, n = 5; inpatient, n = 0).
      LIMITATIONS: The studies were primarily observational in nature. CONCLUSIONS:
      Parents frequently make errors related to knowledge and execution of inpatient
      and ED discharge instructions. Researchers in the future should assess parental
      management of instructions for domains that are less well studied and focus on
      the design of interventions to improve discharge plan management.

PMID- 28739658
TI  - Benchmarking Relatedness Inference Methods with Genome-Wide Data from Thousands
      of Relatives.
AB  - Inferring relatedness from genomic data is an essential component of genetic
      association studies, population genetics, forensics, and genealogy. While
      numerous methods exist for inferring relatedness, thorough evaluation of these
      approaches in real data has been lacking. Here, we report an assessment of 12
      state-of-the-art pairwise relatedness inference methods using a data set with
      2485 individuals contained in several large pedigrees that span up to six
      generations. We find that all methods have high accuracy (92-99%) when detecting
      first- and second-degree relationships, but their accuracy dwindles to <43% for
      seventh-degree relationships. However, most identical by descent (IBD) segment
      based methods inferred seventh-degree relatives correct to within one relatedness
      degree for >76% of relative pairs. Overall, the most accurate methods are
      Estimation of Recent Shared Ancestry (ERSA) and approaches that compute total IBD
      sharing using the output from GERMLINE and Refined IBD to infer relatedness.
      Combining information from the most accurate methods provides little accuracy
      improvement, indicating that novel approaches, such as new methods that leverage
      relatedness signals from multiple samples, are needed to achieve a sizeable jump
      in performance.

PMID- 28739659
TI  - The Stress-Sensing TORC2 Complex Activates Yeast AGC-Family Protein Kinase Ypk1
      at Multiple Novel Sites.
AB  - Yeast (Saccharomyces cerevisiae) target of rapamycin (TOR) complex 2 (TORC2) is a
      multi-subunit plasma membrane-associated protein kinase and vital growth
      regulator. Its essential functions are exerted via phosphorylation and
      stimulation of downstream protein kinase Ypk1 (and its paralog Ypk2). Ypk1
      phosphorylates multiple substrates to regulate plasma membrane lipid and protein
      composition. Ypk1 function requires phosphorylation of Thr504 in its activation
      loop by eisosome-associated Pkh1 (and its paralog Pkh2). For cell survival under
      certain stresses, however, Ypk1 activity requires further stimulation by TORC2
      mediated phosphorylation at C-terminal sites, dubbed the "turn" (Ser644) and
      "hydrophobic" (Thr662) motifs. Here we show that four additional C-terminal sites
      are phosphorylated in a TORC2-dependent manner, collectively defining a minimal
      consensus. We found that the newly identified sites are as important for Ypk1
      activity, stability, and biological function as Ser644 and Thr662. Ala
      substitutions at the four new sites abrogated the ability of Ypk1 to rescue the
      phenotypes of Ypk1 deficiency, whereas Glu substitutions had no ill effect.
      Combining the Ala substitutions with an N-terminal mutation (D242A), which has
      been demonstrated to bypass the need for TORC2-mediated phosphorylation, restored
      the ability to complement a Ypk1-deficient cell. These findings provide new
      insights about the molecular basis for TORC2-dependent activation of Ypk1.

PMID- 28739661
TI  - Histone Acetylation, Not Stoichiometry, Regulates Linker Histone Binding in
      Saccharomyces cerevisiae.
AB  - Linker histones play a fundamental role in shaping chromatin structure, but how
      their interaction with chromatin is regulated is not well understood. In this
      study, we used a combination of genetic and genomic approaches to explore the
      regulation of linker histone binding in the yeast, Saccharomyces cerevisiae We
      found that increased expression of Hho1, the yeast linker histone, resulted in a
      severe growth defect, despite only subtle changes in chromatin structure.
      Further, this growth defect was rescued by mutations that increase histone
      acetylation. Consistent with this, genome-wide analysis of linker histone
      occupancy revealed an inverse correlation with histone tail acetylation in both
      yeast and mouse embryonic stem cells. Collectively, these results suggest that
      histone acetylation negatively regulates linker histone binding in S. cerevisiae
      and other organisms and provide important insight into how chromatin structure is
      regulated and maintained to both facilitate and repress transcription.

PMID- 28739660
TI  - A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel
      Renal Agenesis Gene in Humans.
AB  - Renal agenesis (RA) is one of the more extreme examples of congenital anomalies
      of the kidney and urinary tract (CAKUT). Bilateral renal agenesis is almost
      invariably fatal at birth, and unilateral renal agenesis can lead to future
      health issues including end-stage renal disease. Genetic investigations have
      identified several gene variants that cause RA, including EYA1, LHX1, and WT1
      However, whereas compound null mutations of genes encoding alpha and gamma
      retinoic acid receptors (RARs) cause RA in mice, to date there have been no
      reports of variants in RAR genes causing RA in humans. In this study, we carried
      out whole exome sequence analysis of two families showing inheritance of an RA
      phenotype, and in both identified a single candidate gene, GREB1L Analysis of a
      zebrafish greb1l loss-of-function mutant revealed defects in the pronephric
      kidney just prior to death, and F0 CRISPR/Cas9 mutagenesis of Greb1l in the mouse
      revealed kidney agenesis phenotypes, implicating Greb1l in this disorder. GREB1L
      resides in a chromatin complex with RAR members, and our data implicate GREB1L as
      a coactivator for RARs. This study is the first to associate a component of the
      RAR pathway with renal agenesis in humans.

PMID- 28739663
TI  - Editors' Note.

PMID- 28739662
TI  - Disruptive technology disorder: A past, present, and future neurologic syndrome.
AB  - Based upon an analysis of 6 major historical technological advances over the last
      150 years, a new syndrome, disruptive technology disorder (DTD), is introduced.
      DTD describes the human health ailments that accompany the implementation of
      disruptive technologies. Elevator sickness, railway spine, and bicycle face are
      representative examples. Though the underlying causative disruptive technologies
      may differ, many neurologic symptoms (headache, dizziness, weakness) are common
      to multiple DTDs. Born of technology-driven societal change, DTDs manifest as a
      complex interplay between biological and psychological symptoms.

PMID- 28739664
TI  - Letter re: Neonatal vitamin D status and risk of multiple sclerosis: A population
      based case-control study.

PMID- 28739665
TI  - Letter re: Neonatal vitamin D status and risk of multiple sclerosis: A population
      based case-control study.

PMID- 28739666
TI  - Author response: Neonatal vitamin D status and risk of multiple sclerosis: A
      population-based case-control study.

PMID- 28739667
TI  - Balo concentric sclerosis evolving from apparent tumefactive demyelination.

PMID- 28739668
TI  - Clinical Reasoning: A man with rapidly ascending paralysis.

PMID- 28739669
TI  - Mystery Case: CNS posttransplant lymphoproliferative disorder.

PMID- 28739670
TI  - Teaching NeuroImages: The Charcot shoulder: Chiari malformation with
      syringomyelia associated with arthropathy.

PMID- 28739672
TI  - Body mass index in early life and stroke in adult life: What is the risk?

PMID- 28739671
TI  - Teaching NeuroImages: Three complications of small-cell lung cancer involving the
      brain.

PMID- 28739673
TI  - Trade is central to achieving the sustainable development goals: a case study of
      antimicrobial resistance.

PMID- 28739674
TI  - Essential Role of the Cytoplasmic Chemoreceptor TlpT in the De Novo Formation of
      Chemosensory Complexes in Rhodobacter sphaeroides.
AB  - Bacterial chemosensory proteins form large hexagonal arrays. Several key features
      of chemotactic signaling depend on these large arrays, namely, cooperativity
      between receptors, sensitivity, integration of different signals, and adaptation.
      The best-studied arrays are the membrane-associated arrays found in most
      bacteria. Rhodobacter sphaeroides has two spatially distinct chemosensory arrays,
      one is transmembrane and the other is cytoplasmic. These two arrays work together
      to control a single flagellum. Deletion of one of the soluble chemoreceptors,
      TlpT, results in the loss of the formation of the cytoplasmic array. Here, we
      show the expression of TlpT in a tlpT deletion background results in the
      reformation of the cytoplasmic array. The number of arrays formed is dependent on
      the cell length, indicating spatial limitations on the number of arrays in a cell
      and stochastic assembly. Deletion of PpfA, a protein required for the positioning
      and segregation of the cytoplasmic array, results in slower array formation upon
      TlpT expression and fewer arrays, suggesting it accelerates cluster
      assembly.IMPORTANCE Bacterial chemosensory arrays are usually membrane associated
      and consist of thousands of copies of receptors, adaptor proteins, kinases, and
      adaptation enzymes packed into large hexagonal structures. Rhodobacter
      sphaeroides also has cytoplasmic arrays, which divide and segregate using a
      chromosome-associated ATPase, PpfA. The expression of the soluble chemoreceptor
      TlpT is shown to drive the formation of the arrays, accelerated by PpfA. The
      positioning of these de novo arrays suggests their position is the result of
      stochastic assembly rather than active positioning.

PMID- 28739675
TI  - Identification of the Regulon of AphB and Its Essential Roles in LuxR and
      Exotoxin Asp Expression in the Pathogen Vibrio alginolyticus.
AB  - In Vibrio species, AphB is essential to activate virulence cascades by sensing
      low-pH and anaerobiosis signals; however, its regulon remains largely unknown.
      Here, AphB is found to be a key virulence regulator in Vibrio alginolyticus, a
      pathogen for marine animals and humans. Chromatin immunoprecipitation followed by
      high-throughput DNA sequencing (ChIP-seq) enabled the detection of 20 loci in the
      V. alginolyticus genome that contained AphB-binding peaks. An AphB-specific
      binding consensus was confirmed by electrophoretic mobility shift assays (EMSAs),
      and the regulation of genes flanking such binding sites was demonstrated using
      quantitative real-time PCR analysis. AphB binds directly to its own promoter and
      positively controls its own expression in later growth stages. AphB also
      activates the expression of the exotoxin Asp by binding directly to the promoter
      regions of asp and the master quorum-sensing (QS) regulator luxR DNase I
      footprinting analysis uncovered distinct AphB-binding sites (BBS) in these
      promoters. Furthermore, a BBS in the luxR promoter region overlaps that of LuxR
      binding site I, which mediates the positive control of luxR promoter activity by
      AphB. This study provides new insights into the AphB regulon and reveals the
      mechanisms underlying AphB regulation of physiological adaptation and QS
      controlled virulence in V. alginolyticusIMPORTANCE In this work, AphB is
      determined to play essential roles in the expression of genes associated with QS,
      physiology, and virulence in V. alginolyticus, a pathogen for marine animals and
      humans. AphB was found to bind directly to 20 genes and control their expression
      by a 17-bp consensus binding sequence. Among the 20 genes, the aphB gene itself
      was identified to be positively autoregulated, and AphB also positively
      controlled asp and luxR expression. Taken together, these findings improve our
      understanding of the roles of AphB in controlling physiological adaptation and QS
      controlled virulence gene expression.

PMID- 28739677
TI  - Correction: Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous
      recombination repair in cancer cells.

PMID- 28739676
TI  - SHAPE analysis of the htrA RNA thermometer from Salmonella enterica.
AB  - RNA thermometers regulate expression of some genes involved in virulence of
      pathogenic bacteria such as Yersinia, Neisseria, and Salmonella They often
      function through temperature-dependent conformational changes that alter
      accessibility of the ribosome-binding site. The 5'-untranslated region (UTR) of
      the htrA mRNA from Salmonella enterica contains a very short RNA thermometer. We
      have systematically characterized the structure and dynamics of this thermometer
      at single-nucleotide resolution using SHAPE (selective 2'-hydroxyl acylation
      analyzed by primer extension) assays. Our results confirm that the htrA
      thermometer adopts the predicted hairpin conformation at low temperatures, with
      conformational change occurring over a physiological temperature regime. Detailed
      SHAPE melting curves for individual nucleotides suggest that the thermometer
      unfolds in a cooperative fashion, with nucleotides from both upper and lower
      portions of the stem gaining flexibility at a common transition temperature.
      Intriguingly, analysis of an extended htrA 5' UTR sequence revealed not only the
      presence of the RNA thermometer, but also an additional, stable upstream
      structure. We generated and analyzed point mutants of the htrA thermometer,
      revealing elements that modulate its stability, allowing the hairpin to melt
      under the slightly elevated temperatures experienced during the infection of a
      warm-blooded host. This work sheds light on structure-function relationships in
      htrA and related thermometers, and it also illustrates the utility of SHAPE
      assays for detailed study of RNA thermometer systems.

PMID- 28739678
TI  - MEIS homeodomain proteins facilitate PARP1/ARTD1-mediated eviction of histone H1.
AB  - Pre-B-cell leukemia homeobox (PBX) and myeloid ecotropic viral integration site
      (MEIS) proteins control cell fate decisions in many physiological and
      pathophysiological contexts, but how these proteins function mechanistically
      remains poorly defined. Focusing on the first hours of neuronal differentiation
      of adult subventricular zone-derived stem/progenitor cells, we describe a
      sequence of events by which PBX-MEIS facilitates chromatin accessibility of
      transcriptionally inactive genes: In undifferentiated cells, PBX1 is bound to the
      H1-compacted promoter/proximal enhancer of the neuron-specific gene doublecortin
      (Dcx) Once differentiation is induced, MEIS associates with chromatin-bound PBX1,
      recruits PARP1/ARTD1, and initiates PARP1-mediated eviction of H1 from the
      chromatin fiber. These results for the first time link MEIS proteins to PARP
      regulated chromatin dynamics and provide a mechanistic basis to explain the
      profound cellular changes elicited by these proteins.

PMID- 28739680
TI  - BDNF: An Oncogene or Tumor Suppressor?
AB  - Neurotrophins are a family of growth factors that are vital to the proper
      development of the central nervous system. Their effects on cells are governed by
      the expression and activation of the tyrosine kinase receptors TrkA, TrkB and
      TrkC. TrkB has been immensely implicated in mediating neuronal migration,
      development and differentiation. It has also been shown to protect several
      neuronal cell types from an array of cytotoxic stressors after activation by its
      conjugate ligand brain-derived neurotrophic factor (BDNF). Over the past two
      decades, it has been shown that TrkB and BDNF are up-regulated in many types of
      cancers, conferring aggressive phenotypes underpinned by their resistance to
      several standard chemotherapeutic agents. This resistance to chemotherapy is
      modulated by the downstream targets of the TrkB receptor which include the well
      characterized PI3K /Akt growth pathway, a hallmark of uncontrolled cancer cell
      growth and proliferation. Pre-clinical efforts to develop inhibitors of this
      receptor are promising, and such inhibitors also seem to sensitize cancer cells
      to standard chemotherapies. However, new evidence suggests that BDNF
      overexpression in the hypothalamus has immunoaugmenting properties, eliciting an
      increased anti-tumor immune response and reducing the activity of several
      proteins that would normally confer resistance to chemotherapeutic agents. In the
      current work, we provide a global analysis of the physiological consequences of
      TrkB receptor activation in vitro and discuss the dynamic consequences of TrkB
      activation in vivo. Finally, we propose a clinically-feasible option for
      increasing BDNF expression in the hypothalamus to more readily utilize the
      oncolytic effects of BDNF.

PMID- 28739679
TI  - Two populations of cytoplasmic dynein contribute to spindle positioning in C.
      elegans embryos.
AB  - The position of the mitotic spindle is tightly controlled in animal cells as it
      determines the plane and orientation of cell division. Contacts between
      cytoplasmic dynein and astral microtubules (MTs) at the cell cortex generate
      pulling forces that position the spindle. An evolutionarily conserved Galpha-GPR
      1/2Pins/LGN-LIN-5Mud/NuMA cortical complex interacts with dynein and is required
      for pulling force generation, but the dynamics of this process remain unclear. In
      this study, by fluorescently labeling endogenous proteins in Caenorhabditis
      elegans embryos, we show that dynein exists in two distinct cortical populations.
      One population directly depends on LIN-5, whereas the other is concentrated at MT
      plus ends and depends on end-binding (EB) proteins. Knockout mutants lacking all
      EBs are viable and fertile and display normal pulling forces and spindle
      positioning. However, EB protein-dependent dynein plus end tracking was found to
      contribute to force generation in embryos with a partially perturbed dynein
      function, indicating the existence of two mechanisms that together create a
      highly robust force-generating system.

PMID- 28739681
TI  - Vitamin D Receptor Polymorphism and Cancer: An Update.
AB  - BACKGROUND: Vitamin D mediates its action via vitamin D receptor (VDR) and is
      involved in a wide variety of biological processes including regulation of cell
      proliferation and differentiation in normal tissue and apoptosis, and cell
      adhesion in tumor cells. The study of genetic variations in VDR may elucidate the
      association of vitamin D levels, its metabolism, and VDR polymorphism with
      various diseases and cancer. The association of VDR polymorphism with cancer has
      been reported; however, the literature lacks critical analyses of the studies in
      last 3 years. MATERIALS AND METHODS: A systematic search of PubMed database (2015
      through mid-2017) was conducted to provide a comprehensive overview of this
      clinical arena. RESULTS: Studies on the association of VDR polymorphisms FokI,
      BsmI, TaqI, and ApaI and cancer have suggested the involvement of VDR
      polymorphism in tumorigenesis. CONCLUSION: The inconsistent results and lack of
      the studies in some cancer types warrant additional research.

PMID- 28739682
TI  - Lower Body Lymphedema in Patients with Gynecologic Cancer.
AB  - Lower body lymphedema is a chronic condition and a significant cause of morbidity
      following treatment of gynecologic cancer that strongly impacts patients' quality
      of life (QoL). Most studies on secondary lymphedema have been performed on the
      upper limb after breast cancer treatment and much less is known about lower body
      lymphedema after gynecologic malignancies. This review focuses on secondary
      lymphedema due to gynecologic cancer treatment, analyzing its incidence in the
      different types of gynecologic cancer, diagnosis, risk factors, impact on QoL and
      treatment. A systematic search of Medline has been performed to track the studies
      evaluating lower body lymphedema after treatment for endometrial, ovarian,
      cervical and vulvar cancer. Unfortunately, there is no consensus about a uniform
      evaluation and, as a consequence, the reported incidence is broadly different
      among the studies. Standardization in lymphedema evaluation is required to better
      compare the outcome of different types of treatment.

PMID- 28739683
TI  - Genotoxicity Induced by Dental Materials: A Comprehensive Review.
AB  - Genotoxicity is the capacity of an agent to produce damage in the DNA molecule.
      Considering the strong evidence for a relationship between genetic damage and
      carcinogenesis, evaluation of genotoxicity induced by dental materials is
      necessary for elucidating the true health risks to patients and professionals.
      The purpose of this article was to provide a comprehensive review of genotoxicity
      induced by dental materials. All published data showed some evidence of
      genotoxicity, especially related to dental bleaching, restorative materials and
      endodontic compounds. Certainly, such information will be added to that already
      established for regulatory purposes as a safe way to promote oral healthcare and
      prevent oral carcinogenesis.

PMID- 28739684
TI  - Impact of Parental Cancer on Children.
AB  - BACKGROUND/AIM: The majority of cancers affect the elderly, but 22.4% of all
      cases occur in the ages of 21-55. This age range represents common childbearing
      and child-rearing years, which imply that many of these patients have minor
      children. Approximately 2.85 million children under 18 live with a parent
      affected by cancer. MATERIALS AND METHODS: The Pubmed and Google Scholar were
      searched to identify literature on impact of parental cancer on children and
      potential interventions to support parents and children. RESULTS: We reviewed
      impact of parental cancer on daily routine, role changes, emotional problems and
      social functioning of children. We also discuss interventions that may be useful
      for parents and children. CONCLUSION: It is essential that we learn more about
      the impact of parental cancer on children and ways to support the families using
      evidence-based interventions.

PMID- 28739685
TI  - High alphav Integrin Level of Cancer Cells Is Associated with Development of
      Brain Metastasis in Athymic Rats.
AB  - BACKGROUND/AIM: Brain metastases commonly occur in patients with malignant skin,
      lung and breast cancers resulting in high morbidity and poor prognosis. Integrins
      containing an alphav subunit are cell adhesion proteins that contribute to cancer
      cell migration and cancer progression. We hypothesized that high expression of
      alphav integrin cell adhesion protein promoted metastatic phenotypes in cancer
      cells. MATERIALS AND METHODS: Cancer cells from different origins were used and
      studied regarding their metastatic ability and intetumumab, anti-alphav integrin
      mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases
      animal models. RESULTS: The number of brain metastases and the rate of occurrence
      were positively correlated with cancer cell alphav integrin levels. High alphav
      integrin-expressing cancer cells showed significantly faster cell migration rate
      in vitro than low alphav integrin-expressing cells. Intetumumab significantly
      inhibited cancer cell migration in vitro regardless of alphav integrin expression
      level. Overexpression of alphav integrin in cancer cells with low alphav integrin
      level accelerated cell migration in vitro and increased the occurrence of brain
      metastases in vivo. CONCLUSION: alphav integrin promotes brain metastases in
      cancer cells and may mediate early steps in the metastatic cascade, such as
      adhesion to brain vasculature. Targeting alphav integrin with intetumumab could
      provide clinical benefit in treating cancer patients who develop metastases.

PMID- 28739686
TI  - Chemoprevention by Quercetin of Oral Squamous Cell Carcinoma by Suppression of
      the NF-kappaB Signaling Pathway in DMBA-treated Hamsters.
AB  - BACKGROUND/AIM: The aim of this study was to investigate the effects of the
      flavonoid quercetin on chemoprevention of oral squamous cell carcinoma (OSCC).
      The study involved molecular signaling pathways in 7,12-dimethylbenz(a)
      anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. MATERIALS
      AND METHODS: DMBA (0.5%) was painted at the right buccal pouches of hamsters for
      14 weeks to induce carcinoma. DMBA-treated hamsters received simultaneous doses
      of quercetin. Animals without DMBA induction were used as normal controls. The
      incidence of OSCC and the severity of pre-malignant lesions were determined
      histologically. Apoptosis in the pouch tissue was determined by TUNEL staining.
      The mRNA and protein expression of NF-kappaB p50 and p65, as well as Bcl-2 and
      Bax genes were analyzed using RT-PCR and Western blotting, respectively. RESULTS:
      Quercetin, at various doses, significantly reduced OSCC incidence and severity of
      hyperplasia and dysplasia compared to the DMBA-induction-only group (p<0.01).
      Apoptosis was induced by quercetin treatment compared to the DMBA-induction-only
      group (p<0.01). mRNA and protein expression of NF-kappaB p50, p65 as well as Bcl
      2 genes were significantly suppressed by quercetin at high doses compared to DMBA
      induction only (p<0.05). However, mRNA and protein expression of the Bax gene was
      increased by quercetin treatment at medium and high doses, compared to the DMBA
      induction-only group (p<0.05). Quercetin significantly reduced body-weight loss
      compared to the DMBA-induction-only group (p<0.05). CONCLUSION: Quercetin reduced
      tumor incidence and induced apoptosis through modulation of NF-kappaB signaling
      and its target genes Bcl-2 and Bax in the DMBA-induced carcigenesis hamster
      model, suggesting the potential of quercetin as a candidate for OSCC
      chemoprevention.

PMID- 28739687
TI  - Rational Design of a Potent Pan-Pim Kinases Inhibitor with a Rhodanine
      Benzoimidazole Structure.
AB  - BACKGROUND/AIM: The serine/threonine Pim kinases are overexpressed in various
      types of solid carcinomas and hematological malignancies, and contribute to
      regulating cell-cycle progression and cell survival. The aim of this study was to
      discover a novel pan-Pim kinases inhibitor with potent anti-proliferative
      activities against cancer cell lines. MATERIALS AND METHODS: We screened a panel
      of small molecule compounds for their ability to inhibit Pim-1 kinase activity,
      and the hit compound was optimized using the docking analysis to Pim-1. We
      evaluated kinase-inhibition activities of the rationally-designed compound
      against Pim-1, 2, 3 and another five kinases. Furthermore, in order to
      characterize the cellular activities, both solid and hematological cancer cell
      lines treated with the compound were subjected to anti-proliferative assay,
      western blotting, FACS and apoptosis assays. RESULTS: We discovered a pan-Pim
      kinases inhibitor, compound 1, with a rhodanine-benzylidene structure via Pim-1
      inhibitor screening. Using docking analysis of compound 1 and Pim-1, we optimized
      it and found a potent- and selective-Pim kinases inhibitor, compound 2, with a
      rhodanine-benzoimidazole structure. Compound 2 inhibited Pim-1, 2, 3 with IC50
      values of 16, 13, and 6.4 nM, respectively, and suppressed proliferation of solid
      and hematological cancer cell lines at submicromolar concentrations. In both
      types of cell lines, compound 2 inhibited phosphorylation of Pim signaling
      substrates and cell-cycle progression and induced apoptosis. CONCLUSION: We
      identified a pan-Pim kinases inhibitor, compound 2, with a rhodanine
      benzoimidazole structure. Our data suggest that compound 2 can serve as a lead to
      novel anticancer agents, effective in the treatment of both solid carcinomas and
      hematological malignancies.

PMID- 28739688
TI  - Cyclooxygenase-2 Inhibition Enhances Proliferation of NKT Cells Derived from
      Patients with Laryngeal Cancer.
AB  - BACKGROUND/AIM: The aim of this study was to analyze whether inhibition of
      cyclooxygenase-2 by celecoxib and the subsequent enhancement in the proliferation
      of natural killer T (NKT) cells could play a role in dendritic cell (DC)-based
      laryngeal cancer (LC) immunotherapy. PATIENTS AND METHODS: Peripheral blood
      mononuclear cells were obtained from 48 male patients diagnosed with LC and 30
      control patients without cancer disease. Neoplastic cell lysate preparations were
      made from cancer tissues obtained after surgery and used for in vitro DCs
      generation. NKT cells proliferation assay was performed based on 3H-thymidine
      incorporation assay. RESULTS: An increased proliferation of NKT cells was
      obtained from control patients compared to NKT cells obtained from LC patients
      regardless of the type of stimulation or treatment. In the patient group
      diagnosed with LC, COX-2 inhibition resulted in a significantly enhanced
      proliferation of NKT cells when stimulated with autologous DCs than NKT cells
      stimulated with DCs without COX-2 inhibition. These correlations were not present
      in the control group. Higher proliferation rate of NKT cells was also observed in
      non-metastatic and highly differentiated LC, which was independent of the type of
      stimulation or treatment. CONCLUSION: COX-2 inhibition could be regarded as
      immunotherapy-enhancing tool in patients with LC.

PMID- 28739689
TI  - LXR Activation Down-regulates Lipid Raft Markers FLOT2 and DHHC5 in MCF-7 Breast
      Cancer Cells.
AB  - BACKGROUND/AIM: Lipid rafts are cholesterol-enriched microdomains of the plasma
      membrane. Recent studies have underlined that their integrity is critical for
      cancer cell survival. Liver X receptor (LXR) has a central role in cellular
      cholesterol homeostasis and its stimulation inhibits proliferation of several
      cancer cell lines. This study investigated whether LXR could modulate lipid rafts
      integrity and consequently alter proliferation of the MCF-7 breast cancer cell
      line. MATERIALS AND METHODS: Effect of LXR agonist T0901317 on integrity of MCF-7
      lipid rafts was examined by studying the expression of rafts marker flotillin-2
      (FLOT2) and DHHC5, which palmitoylates FLOT2, and by studying the expression of
      phospho-Akt. RESULTS: We demonstrated that LXR stimulation decreases mRNA and
      protein expression of FLOT2 and DHHC5 in MCF-7 cells. LXR stimulation also
      reduces Akt phosphorylation and its localization at the plasma membrane.
      CONCLUSION: We showed, for the first time, that LXR regulates transcription of
      specific proteins of lipid rafts in a breast cancer model.

PMID- 28739690
TI  - Nicotine Exposure Augments Renal Toxicity of 5-aza-cytidine Through p66shc:
      Prevention by Resveratrol.
AB  - BACKGROUND/AIM: We have shown that either chronic nicotine (NIC) exposure or 5
      aza-cytidine (AZA) augments oxidative stress-dependent injury through stimulating
      p66shc in renal cells. Hence, NIC could exacerbate adverse effects of AZA while
      antioxidants such as resveratrol (RES) could prevent it. MATERIALS AND METHODS:
      Renal proximal tubule cells (NRK52E) were treated with 20 MUM RES prior to 200
      MUM NIC plus 100 nM AZA and cell injury (LDH release) was determined. Reporter
      luciferase assays determined p66shc activation and RES-induced antioxidant
      responses. Genetic manipulations identified the mechanism of RES action. RESULTS:
      NIC exacerbated AZA-dependent injury via augmenting p66shc transcription. While
      RES suppressed NIC+AZA-mediated injury, -surprisingly-it further enhanced
      activity of the p66shc promoter. RES protected cells via the cytoplasmic
      p66shc/Nrf2/heme oxygenase-1 (HO-1) axis. CONCLUSION: RES can protect the kidney
      from adverse effects of NIC in patients undergoing anticancer therapy.

PMID- 28739691
TI  - Efficacy In Vitro of Caffeine and Valproic Acid on Patient-Derived
      Undifferentiated Pleomorphic Sarcoma and Rhabdomyosarcoma Cell Lines.
AB  - BACKGROUND/AIM: We have previously reported that caffeine (CAF) can enhance
      chemotherapy efficacy of bone and soft-tissue sarcoma established cell lines via
      cell-cycle perturbation. We subsequently tested the combination of valproic acid
      (VPA), a histone deacetylase (HDAC) inhibitor, with caffeine on established human
      osteosarcoma cells in vitro. Both VPA and CAF caused concentration-dependent cell
      death of the osteosarcoma cell lines in vitro, and their combination was
      synergistic. We subsequently established patient-derived cell lines from
      undifferentiated pleomorphic sarcoma (UPS) and rhabdomyosarcoma (RMS), both of
      which are recalcitrant cancers. These cell lines are termed AC-UPS01 and AC
      RMS01, respectively. MATERIALS AND METHODS: In the present study, we tested CAF
      and VPA and their combination on the two patient-derived sarcoma cell lines. Cell
      survival after a 72 h exposure to each drug was determined by the WST-8 assay.
      IC50 values were calculated for each drug. RESULTS: CAF and VPA caused
      concentration-dependent cytocidal efficacy for both cell lines. The IC50 for CAF
      for AC-UPS01 was 2.02 +/- 0.22 mM. The IC50 for VPA for AC-UPS01 was 9.54 +/-
      1.44 mM. The IC50 for CAF for AC-RMS01 was 2.37 +/- 0.48 mM. The IC50 for VPA for
      AC-RMS01 was 2.13 +/- 0.20 mM. Synergistic efficacy of combination treatment of
      CAF and VPA was also observed for both cell lines. CONCLUSION: The results of the
      present study suggest that CAF and VPA may be useful in the treatment of
      recalcitrant sarcoma.

PMID- 28739692
TI  - WNT/beta-Catenin Signaling Inhibitor IC-2 Suppresses Sphere Formation and
      Sensitizes Colorectal Cancer Cells to 5-Fluorouracil.
AB  - BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most malignant types of
      cancer worldwide. Recent studies suggest that a small subpopulation of cells, so
      called cancer stem cells (CSCs), promote the high metastasis and relapse
      associated with CRC. WNT/beta-catenin signaling plays a critical role in CSC
      maintenance. Therefore, its inhibitor may suppress CSCs and improve therapeutic
      effects on CRC. MATERIALS AND METHODS: The effects of a derivative of WNT/beta
      catenin signaling inhibitor, IC-2, which we recently developed, on the CRC cell
      line DLD-1, were examined by luciferase reporter assay, WST assay, western blot,
      and sphere assay. RESULTS: The reporter assay showed that IC-2 reduced WNT/beta
      catenin transcriptional activity in DLD-1 cells. Notably, IC-2 reduced expression
      levels of CSC marker proteins, as well as sphere formation. In addition, IC-2
      increasesd cytotoxicity of 5-fluorouracil (5-FU) in DLD-1 cells. CONCLUSION:
      These results suggest that the combination treatment of IC-2 and 5-FU can
      stimulate tumor-suppressive effects on CRC.

PMID- 28739693
TI  - Correlation Between NKG2DL Expression and Antitumor Effect of Protein-bound
      Polysaccharide-K in Tumor-bearing Mouse Models.
AB  - BACKGROUND/AIM: We investigated the relationship between the expression of
      natural killer group 2, member D ligands (NKG2DLs) and the antitumor effects of
      protein-bound polysaccharide-K (PSK). MATERIALS AND METHODS: PSK was administered
      to evaluate its effectiveness against tumor growth. The expression of Rae-1 and
      H60 were analyzed in multiple cell lines. RESULTS: PSK showed the highest
      antitumor effects in mice implanted with cells expressing neither Rae-1 nor H60.
      PSK had little antitumor effect in mice implanted with cells expressing both Rae
      1 and H60. A correlation between the expression of NKG2DLs and the antitumor
      effect of PSK was observed. After PSK administration, INF-gamma production in
      CD8+ T cells increased in mice with cells expressing neither Rae-1 nor H60, but
      did not change in mice implanted with cells expressing both Rae-1 and H60.
      CONCLUSION: We demonstrated that the expression of NKG2DLs affects tumor immunity
      and the efficacy of immuno therapy in tumor-bearing mouse model.

PMID- 28739694
TI  - Cell Cycle Arrest and Apoptosis Induced by Kinamycin F in Human Osteosarcoma
      Cells.
AB  - BACKGROUND/AIM: Kinamycin F is a bacterial metabolite which contains an unusual
      and potentially reactive diazo group that is known for its ability to inhibit
      cell growth. In this study, the potential anti-tumor activity of kinamycin F was
      investigated in three human osteosarcoma cell lines, MG-63, U-2 OS and HOS as an
      antitumor agent with a potentially novel target. MATERIALS AND METHODS:
      Proliferation and cell viability were measured in three human osteosarcoma cell
      lines by commercially available kits. We also evaluated the effects of the drug
      on cell cycle progression using the MuseTM Cell Analyzer. Caspase-3 activity was
      determined by a fluorometric EnzChek assay kit. Finally, following treatment with
      kinamycin F the protein levels of cyclin D3, cyclin A and cdK-2 were examined.
      RESULTS: Kinamycin F induced a concentration-dependent cell death in all the
      three cell lines. Flow cytometry revealed that kinamycin F treatment at 1 MUM
      concentration significantly increased the cell population in the G2/M-phase (60
      65%). Kinamycin F activated caspase 3 in all the three cell lines, clearly
      demonstrating that the growth inhibitory effect of kinamycin F can be attributed
      to apoptosis induction. Finally, kinamycin F suppressed osteosarcoma cell
      proliferation affecting cyclin A and D3 expression. CONCLUSION: Understanding the
      mechanism by which kinamycin F exerts its ability to inhibit cell growth may be a
      step forward in the development of new therapeutic strategies for the treatment
      of OS.

PMID- 28739695
TI  - Synergistic Effects of Arsenite on Radiosensitization of Glioblastoma Cells.
AB  - BACKGROUND/AIM: Glioblastoma is a frequent type of brain tumor and is
      radioresistant. Arsenite, which crosses the blood-brain barrier, shows
      synergistic effects with radiation in vitro and in vivo. The mechanism remains
      unclear. MATERIALS AND METHODS: As synergistic radiosensitization has been
      reported in p53-deficient cancer cells, radiosensitization was evaluated using
      the glioblastoma cell line, U87MG-E6, which harbors inactivated p53, in
      comparison with the cell line, HCT116 p53 (-/-). Radiosensitivity was evaluated
      using clonogenic assays and detection of abnormal amplification of centrosomes
      (AAC). RESULTS: Synergistic effects of arsenite on radiosensitivity were observed
      in both cell lines. The radiosensitization induced by arsenite was abolished by N
      acetyl-l-cysteine, a reactive oxygen species (ROS) scavenger. Increased
      radiosensitivity by arsenite was also abolished following knock-down of BRCA2. In
      addition, the increased radiosensitization by arsenite was correlated with AAC,
      which was abolished by BRCA2 knock-down. CONCLUSION: We conclude that
      radiosensitization by arsenite is related to ROS and BRCA2 function.

PMID- 28739696
TI  - Differences in Extracellular Matrix Composition and its Role in Invasion in
      Primary and Secondary Intracerebral Malignancies.
AB  - BACKGROUND/AIM: The most common malignant primary brain tumor is glioblastoma
      which infiltrates the peritumoral brain, while secondary brain metastases are
      well demarcated malignancies. Previous research has proved the pivotal role of
      the changes in the extracellular matrix (ECM) in cancer cell invasion. MATERIALS
      AND METHODS: The mRNA expression of 40 ECM molecules was determined using qRT-PCR
      in 54 fresh-frozen glioblastoma and brain metastasis samples. Seventy-two samples
      were used to determine the levels of 20 ECM proteins. RESULTS: The mRNA and
      protein expression pattern of the studied tumors differs greatly. Linear
      discriminant analysis of mRNA expression identified samples based on their mRNA
      expression profile with 92.3% probability and highlighted the role of some
      molecules as their level greatly influenced sample identification. CONCLUSION:
      Different tumor types with different invasiveness differ in the composition of
      their ECM and this can be used to identify samples. Furthermore, some ECM
      molecules greatly contribute to tumor invasiveness and could be targets of anti
      invasive oncotherapy.

PMID- 28739697
TI  - Z-360 Suppresses Tumor Growth in MIA PaCa-2-bearing Mice via Inhibition of
      Gastrin-induced Anti-Apoptotic Effects.
AB  - BACKGROUND/AIM: The aim of the study was to evaluate the anti-tumor mechanism of
      Z-360, a gastrin/cholecystokinin-2 receptor (CCK2R) antagonist, in MIA PaCa-2
      cells and in a subcutaneous xenograft mice model. MATERIALS AND METHODS: The anti
      tumor effects of Z-360 and/or gemcitabine were monitored using a MIA PaCa-2
      xenograft model. The effect of Z-360 on apoptosis in the model was examined by
      TUNEL staining and real-time PCR analysis and the effect in MIA PaCa-2 cells
      stably expressing human CCK2R was also evaluated by caspase-3/7 activity.
      RESULTS: In this xenograft model, Z-360 significantly reduced the tumor weight,
      increased TUNEL-positive cells and suppressed the expression of anti-apoptosis
      factors such as survivin, XIAP and Mcl-1, and these effects of Z-360 combined
      with gemcitabine were more effective. Furthermore, gastrin-17 and gastrin-34
      inhibited apoptosis in vitro and Z-360 dose-dependently abrogated this effect.
      CONCLUSION: These results suggest that Z-360 exerts an anti-tumor effect through
      a reduction in anti-apoptosis factors by blocking CCK2R.

PMID- 28739698
TI  - Highly Eribulin-resistant KBV20C Oral Cancer Cells Can Be Sensitized by Co
      treatment with the Third-generation P-Glycoprotein Inhibitor, Elacridar, at a Low
      Dose.
AB  - BACKGROUND/AIM: Eribulin mesylate, also called Halaven(r) (HAL), was recently
      developed as a microtubule-targeting drug and is used in the clinic for resistant
      or metastatic cancer. Previously, we showed that P-glycoprotein (P-gp)
      overexpressing KBV20C oral cancer cells are highly resistant to HAL compared to
      sensitive KB cells. This qualitative study was designed to identify specific P-gp
      inhibitors that increase the sensitivity of highly resistant cancer cells to HAL.
      MATERIALS AND METHODS: In order to identify functional P-gp inhibitors, HAL
      treated KBV20C cells were co-treated with P-gp inhibitors, verapamil, elacridar,
      cyclosporine A, mitotane, piperine, fumagillin, curcumin, indomethacin,
      probenecid, sulindac, tesmilifene, and C-4. We then evaluated which P-gp
      inhibitors required a low dose to sensitize KBV20C cells to HAL. We also
      determined whether a low dose of a P-gp inhibitor could inhibit P-gp efflux
      pumping. RESULTS: We found that cyclosporine A sensitized HAL-treated KBV20C
      cells at a low dose, whereas verapamil, another first-generation P-gp inhibitor,
      required a dose that was nearly 10-fold higher. We also found that the natural
      products, piperine and mitotane, sensitized KBV20C cells to HAL co-treatment.
      Interestingly, we found that elacridar, a third-generation P-gp inhibitor,
      sensitized HAL-treated cells at a low dose. Elacridar required approximately a
      500-fold lower dose than that of verapamil to exert a similar effect. All
      inhibitors showed P-gp inhibitory activity that correlated with sensitivity to
      HAL. CONCLUSION: These results suggest that highly HAL-resistant cancer cells can
      be sensitized with cyclosporine A or elacridar, specific P-gp inhibitors that
      exert their effects at a low dose. These findings provide important information
      regarding the sensitization of highly HAL-resistant cells with selective P-gp
      inhibitors and indicate that elacridar may be used to treat such highly HAL
      resistant cancer cells.

PMID- 28739699
TI  - Clinical Significance and Phenotype of MTA1 Expression in Esophageal Squamous
      Cell Carcinoma.
AB  - BACKGROUND/AIM: Metastasis-associated gene 1 (MTA1) is considered a potential
      prognostic factor in esophageal cancer. We investigated the clinical relationship
      between MTA1, LAT1, and tumor metabolism, as evaluated by positron emission
      tomography (PET) in esophageal squamous cell carcinoma. MATERIALS AND METHODS: We
      analyzed 142 esophageal squamous cell carcinoma patients who underwent curative
      resection without preoperative treatment. MTA1 expression was assessed by immuno
      zahistochemistry, and tested against standardized uptake values from preoperative
      PET-CT. The association among MTA1, LAT1, and 18FAMT PET results were analyzed.
      RESULTS: MTA1 staining was observed in 82 of 142 cancer tissues. Five-year
      overall survival was 69.9 % in the absence of MTA1, but 50.7% otherwise
      (p=0.021), while disease-free survival was 66.5% and 49.0% (p=0.071),
      respectively. Abnormal 18FAMT accumulation was noted in 13 patients without MTA1
      and in 18 patients with MTA1 (p=0.079), with maximum standardized uptake value
      1.6+/-1.6 and 2.7+/-1.6, respectively (p=0.036). MTA1 expression was positively
      correlated with LAT1 (p=0.013) and CD34 (p=0.034) expression, but not with Ki-67
      (p=0.078). CONCLUSION: MTA1 shows promise as a diagnostic and prognostic marker
      in esophageal cancer, and we anticipate that the gene will also prove to be a
      good therapeutic target.

PMID- 28739700
TI  - Long-term Oncologic Outcomes of Robotic-assisted Radical Prostatectomy by a
      Single Surgeon.
AB  - AIM: The aim of the study was to evaluate the long-term oncology outcomes of
      prostate cancer patients receiving robotic-assisted radical prostatectomy (RARP).
      PATIENTS AND METHODS: We retrospectively evaluated 111 patients with clinically
      localized prostate cancer receiving RARP with a mean follow-up of 103.43 months.
      RESULTS: The 5-year BCRFS and 8-year BCRFS among low-, intermediate-, and high
      risk patients were 95.5% vs. 77.1% vs. 53.7% and 95.5% vs. 61.2% vs. 48.1%
      (p=0.000). The median time to BCR in these three groups was 122.5, 98.0, and 79.2
      months. Regarding postoperative factors, positive lymph node (HR=3.748, 95%
      CI=1.407-9.984), pathology Gleason score (HR=1.507, 95%CI=1.010-2.248), and
      postoperative nadir PSA <0.003 ng/ml (HR=0.058, 95%CI=0.020-0.166) were
      independent risk factors for BCR. CONCLUSION: D'Amico risk classification was
      effective at predicting biochemical recurrence in patients receiving RARP.
      Furthermore, postoperative risk factors such as metastatic lymph node, pathology
      Gleason score, and nadir PSA <0.003 ng/ml were independent predictors of
      biochemical recurrence.

PMID- 28739701
TI  - The Prognostic Significance of the Tumor-infiltrating Programmed Cell Death-1+ to
      CD8+ Lymphocyte Ratio in Patients with Colorectal Cancer.
AB  - BACKGROUND/AIM: Tumor-infiltrating lymphocytes (TILs) have been reported to
      reflect the antitumor immunity of the host and correlate with the therapeutic
      outcomes and survival. Nowadays TILs are attracting attention as new biomarkers
      of diseases such as colorectal cancer. TILs are classified into several subsets,
      among which CD8+ T cells directly attack cancer cells and play a central role in
      antitumor immunity. A high density of CD8+ TILs has been reported to correlate
      with a better clinical outcome. Programmed cell death-1 (PD-1) is recognized to
      be a surface marker for dysfunction of T lymphocytes. However, the prognostic
      significance of PD-1+ TILs remains unclear. The aim of this study was to evaluate
      the prognostic significance of the number of PD-1+ TILs and the tumor
      infiltrating PD-1+ to CD8+ lymphocyte ratio (PD-1/CD8 ratio) in patients with
      colorectal cancer (CRC). PATIENTS AND METHODS: A total of 90 patients with stage
      II/III CRC who underwent curative surgery were enrolled in this study.
      Immunohistochemistry was used to assess the densities of PD-1+ TILs and CD8+
      TILs. The PD-1/CD8 ratio was defined as the number of PD-1+ TILs divided by the
      number of CD8+ TILs. The optimum cut-off value for the number of PD-1+ TILs and
      the PD-1/CD8 ratio was determined via a receiver operating characteristic
      analysis. We then assessed the prognostic significance of the number of PD-1+
      TILs and the PD-1/CD8 ratio. RESULTS: The relapse-free and overall survival rates
      were significantly worse in the high-PD-1/CD8 ratio group than in the low-PD
      1/CD8 ratio group (relapse-free survival: p=0.0257, overall survival: p=0.0363),
      although the number of PD-1+ TILs showed no prognostic significance. CONCLUSION:
      The PD-1/CD8 ratio may, therefore, be a useful prognostic marker for stage II/III
      CRC. What is important for predicting the prognosis may be the PD-1/CD8 ratio
      rather than the absolute number of PD-1+ TILs.

PMID- 28739702
TI  - Anastrozole-induced Autoimmune Hepatitis: A Rare Complication of Breast Cancer
      Therapy.
AB  - BACKGROUND: Autoimmune hepatitis (AIH) is an extremely rare complication of
      anastrozole therapy. It presents with elevated liver function tests. The
      diagnosis is established by detecting high titers of autoantibodies such as
      antinuclear antibodies, anti-smooth muscle antibodies, and elevated
      immunoglobulins. It is confirmed with a liver biopsy showing interface rosetting
      and an increased number of plasma cells. Early diagnosis of anastrozole-induced
      AIH is important because it allows anastrozole to be discontinued and
      immunomodulatory treatment to be promptly initiated. CASE REPORT: We present the
      case of a 71-year-old female patient diagnosed with early-stage breast cancer.
      The patient developed AIH as a result of treatment with anastrozole. Its
      clinicopathological presentation, diagnosis, and treatment are reviewed.
      CONCLUSION: This case report intends to make clinicians aware of this rare
      complication of anastrozole therapy. AIH should be suspected in any patient on
      anastrozole (and possibly, other aromatase inhibitors) who develops elevated
      liver function tests.

PMID- 28739703
TI  - Cerebrospinal Fluid Penetration Rate and Efficacy of Afatinib in Patients with
      EGFR Mutation-positive Non-small Cell Lung Cancer with Leptomeningeal
      Carcinomatosis: A Multicenter Prospective Study.
AB  - BACKGROUND: Afatinib is an effective first-line treatment for epidermal growth
      factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer
      (NSCLC). However, few reports have addressed the influence of cerebrospinal fluid
      (CSF) penetration rate on the efficacy of afatinib in patients with central
      nervous system metastases. Therefore, we conducted a prospective multicenter
      trial to evaluate the CSF penetration rate and efficacy of afatinib in patients
      with EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis. PATIENTS
      AND METHODS: Eleven patients with histologically-proven EGFR mutation-positive
      NSCLC with leptomeningeal carcinomatosis were enrolled in the study between April
      2014 and November 2015. They were treated with afatinib (40 mg/day), and blood
      and CSF levels of afatinib were analyzed on day 8. The primary endpoint was CSF
      penetration rate. Secondary endpoints included the objective response rate (ORR),
      progression-free survival (PFS), and overall survival (OS). RESULTS: The median
      age of patients was 66 years. Five patients harbored an exon 19 deletion, three
      harbored a p.L858R point mutation, and three harbored an uncommon exon 18
      mutation. The levels of afatinib in blood and CSF (mean+/-SD) were 233.26+/
      195.40 nM and 3.16+/-1.95 nM, respectively. The CSF penetration rate was 2.45+/
      2.91%. The ORR was 27.3% (three out of 11 patients), and two out of these three
      responders had uncommon EGFR mutations. The median PFS and OS were 2.0 and 3.8
      months, respectively. CONCLUSION: The median CSF penetration rate of afatinib was
      higher than previously reported. Afatinib was effective against leptomeningeal
      carcinomatosis particularly in patients with NSCLC harboring uncommon EGFR
      mutations. The criteria for selecting a specific EGFR tyrosine kinase inhibitor
      for therapy of NSCLC should include its ability to penetrate CSF and its efficacy
      against specific mutation types.

PMID- 28739704
TI  - Vaginal and Urine Self-sampling Compared to Cervical Sampling for HPV-testing
      with the Cobas 4800 HPV Test.
AB  - BACKGROUND/AIM: To compare human papillomavirus (HPV) DNA detection in self
      collected vaginal and urine samples with clinician-taken cervical samples in
      relation to histology. MATERIALS AND METHODS: Self-collected vaginal, urine and
      clinician-taken cervical samples were analyzed from 218 women with the Cobas 4800
      HPV test (Roche Molecular Diagnostics). RESULTS: The sensitivity for detection of
      HPV in the vaginal self-sampling test was 96.4% and in urine was 83.9% relative
      to detection by clinician-taken cervical sample. The vaginal self-sampling and
      the clinician-taken HPV tests had the same sensitivity of 92.8% (95% confidence
      interval=86.3-96.8%) and specificity for detection of high-grade squamous
      intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS). Detection in
      urine samples had a sensitivity of 76.3% (95% confidence interval=67.9-84.2%) for
      HSIL/AIS. CONCLUSION: The Cobas 4800 HPV test detects high-grade pre-cancerous
      cervical lesions in self-collected vaginal samples with the same high sensitivity
      as in clinician-taken cervical samples.

PMID- 28739705
TI  - Metabolic Rather than Pathological Response to Preoperative Chemoradiotherapy Is
      a Stronger Predictor of Survival in cStage IIB-IV Esophageal Cancer.
AB  - AIM: We investigated which is the stronger predictor, pathological response or
      metabolic response, for survival outcome in patients treated with neoadjuvant
      chemoradiotherapy (NACRT) plus esophagectomy for thoracic esophageal squamous
      cell carcinoma (TESCC). PATIENTS AND METHODS: Fifty consecutive patients with
      cStage IIB-IV TESCC were enrolled. We analyzed the pathological response and
      metabolic response (fractional decrease in tumor maximum standardized uptake
      value) to NACRT. Independent prognostic factors predictive of 3-year survival
      were investigated using univariate and multivariate analyses. RESULTS: Among the
      50 patients, 10 (20%) showed a pathological complete response (in both tumor and
      lymph nodes) and 36 (72%) showed grade 2-3 pathological response. Univariate
      analysis showed that age, gender, cT stage, pathological response and metabolic
      response to be significant prognostic factors. A subsequent multivariate analysis
      confirmed metabolic response and gender to be significant prognostic factors.
      CONCLUSION: Metabolic response for NACRT was an independent prognostic factor and
      a more powerful predictor of survival compared to pathological response.

PMID- 28739706
TI  - Safety and Effectiveness of Laparoscopic Colorectal Resection in Elderly Patients
      with Colorectal Cancer: A Propensity Score Matching Study.
AB  - BACKGROUND/AIM: The aim of this study was to evaluate the safety and
      effectiveness of laparoscopic surgery in elderly patients with colorectal cancer.
      PATIENTS AND METHODS: In total, 223 patients aged <75 years and 66 patients aged
      >=75 years who underwent laparoscopic colorectal resection were included. Short-
      and long-term outcomes were compared between the younger and elderly patients
      after propensity score matching. RESULTS: Post-operative complications were
      similar in both groups (younger vs. elderly: 24.7% vs. 19.3%, p=0.479). There
      were no significant differences in disease-free survival (DFS) (5-year DFS: 96.3%
      vs. 86.9%, p=0.079) and overall survival (OS) (5-year OS: 92.9% vs. 78.1%,
      p=0.106) between the two groups. CONCLUSION: Laparoscopic surgery for colorectal
      cancer is as safe and effective for elderly patients as for younger patients.

PMID- 28739707
TI  - Early Gastric Cancer Exfoliating into Gastric Lavage (GL1 EGC) Shows a More
      Aggressive Behavior and Poorer Survival Compared to the Non-Exfoliative
      Counterpart (GL0 EGC).
AB  - BACKGROUND/AIM: Early gastric cancer (EGC) is usually associated with excellent
      prognosis. Some cases, however, entail a poorer survival. Our aim was to assess
      if EGC exfoliating into gastric lavage (GL) has a more aggressive behavior than
      the non-exfoliative counterpart. PATIENTS AND METHODS: Between April 2012 and
      April 2017, 96 gastric cancer patients were prospectively submitted to
      preoperative GL to detect the presence (GL1) or absence (GL0) of exfoliated
      malignant cells. RESULTS: A total of 16 patients had EGC. T1b cases had
      significantly poorer overall (OS), progression-free (PFS) and disease-free
      survival (DFS) than their GL0 counterpart (16.3 vs. 61 months, p=0.0032).
      Similarly, the entire T1 class (T1a plus T1b EGCs) showed worse OS, PFS, DFS
      (15.5 vs. 61 months, p=0.0008) and time-to-tumor progression (17 vs. 61 months,
      p=0.0103). CONCLUSION: In the case of EGC, the GL0-GL1 classification should
      become a routine clinical practice to identify the aggressive tumor phenotypes
      requiring for closer follow-up or additional treatment.

PMID- 28739708
TI  - Venous Resection in Pancreatic Ductal Adenocarcinoma: Impact of Surgical
      Experience on Early Postoperative Courses.
AB  - BACKGROUND/AIM: The aim of this study was to determine the effects of surgical
      experience on early postoperative courses after pancreaticoduodenectomy (PD) with
      venous resection. PATIENTS AND METHODS: From 2005 to 2014, 134 patients were
      analyzed, 62 and 72 patients were resected in periods 1 (2005-2009) and 2 (2010
      2014) respectively; 115 and 19 patients underwent PD with venous resection in
      high- and low-volume center groups respectively. RESULTS: Of the entire cohort,
      mortality rate was 4%. There were no significant differences between the two
      periods. In the low-volume center group, the mortality rate was increased (21%
      vs. 2%, p<0.01) and the mean length of hospital stay was longer (25 (+/-27) days
      vs. 17 (+/-8) days, p=0.04). The high-volume center group was the only
      independent protective factor regarding death (OR=0.04, 95%CI (0.01-0.38),
      p<0.01) and length of hospital stay (OR<0.01, 95%CI (0.00-0.43), p=0.03).
      CONCLUSION: Patients who present isolated venous invasion must be referred to
      high-volume centers for surgery.

PMID- 28739709
TI  - Utility of Inflammatory Marker- and Nutritional Status-based Prognostic Factors
      for Predicting the Prognosis of Stage IV Gastric Cancer Patients Undergoing Non
      curative Surgery.
AB  - BACKGROUND/AIM: The present study aimed to compare the utility of various
      inflammatory marker- and nutritional status-based prognostic factors, including
      many previous established prognostic factors, for predicting the prognosis of
      stage IV gastric cancer patients undergoing non-curative surgery. PATIENTS AND
      METHODS: A total of 33 patients with stage IV gastric cancer who had undergone
      palliative gastrectomy and gastrojejunostomy were included in the study.
      Univariate and multivariate analyses were performed to evaluate the relationships
      between the mGPS, PNI, NLR, PLR, the CONUT, various clinicopathological factors
      and cancer-specific survival (CS). RESULTS: Among patients who received non
      curative surgery, univariate analysis of CS identified the following significant
      risk factors: chemotherapy, mGPS and NLR, and multivariate analysis revealed that
      the mGPS was independently associated with CS. CONCLUSION: The mGPS was a more
      useful prognostic factor than the PNI, NLR, PLR and CONUT in patients undergoing
      non-curative surgery for stage IV gastric cancer.

PMID- 28739710
TI  - Discrepancy in Programmed Cell Death-Ligand 1 Between Primary and Metastatic Non
      small Cell Lung Cancer.
AB  - AIM: To investigate the discordance in the programmed cell death-ligand 1 (PD-L1)
      expression between primary and metastatic tumors and analyze the association
      between the discordance and the clinical factors in non-small cell lung cancer
      (NSCLC) patients. PATIENTS AND METHODS: Twenty-one NSCLC patients who underwent
      surgery or biopsy for paired primary and metastatic lesions at our Institution
      from 2005 to 2016 were analyzed. Lesions with the PD-L1 expression being >=5%
      were considered PD-L1-positive. RESULTS: The metastatic sites included the brain
      (n=16), adrenal gland (n=3), spleen (n=1) and jejunum (n=1). Negative conversion
      of the primary PD-L1-positive NSCLC and positive conversion of the primary PD-L1
      negative NSCLC were observed in 3 (14%) and 2 (10%) cases, respectively.
      Radiotherapy for the metastatic brain lesion before its resection showed a
      significant relationship with the positive conversion of the primary PD-L1
      negative NSCLC (p=0.048). CONCLUSION: Radiotherapy-derived effects may contribute
      to the positive conversion of the primary PD-L1-negative NSCLC.

PMID- 28739711
TI  - Adrenal Insufficiency Related to Anti-Programmed Death-1 Therapy.
AB  - BACKGROUND/AIM: Adrenal insufficiency is one of the adverse events (AEs)
      associated with anti-programmed death-1 (PD1) therapy. Delaying diagnoses can
      lead to serious conditions. It is necessary to elucidate detailed clinical
      features of these AEs. PATIENTS AND METHODS: Patients treated with anti-PD-1
      monotherapy or in combination with anti-cytotoxic T cell lymphocyte-4 therapy at
      our hospital from January 2013 to December 2016 were identified. The patients'
      clinical characteristics and laboratory and radiologic findings were collected.
      RESULTS: Adrenal insufficiency occurred in 3% of the patients. All patients were
      male. At the onset of symptoms, eosinophilia (>500/MUl) was observed in four
      cases. Eosinophilia was observed more than a month before onset of symptoms in
      three cases. Other pituitary hormones remained relatively stable. Radiological
      evidence of pituitary inflammation was detected only in one case. CONCLUSION:
      Most anti-PD1-related adrenal insufficiency cases involved an isolated ACTH
      deficiency. Eosinophilia may be an early indicator before the onset of symptoms.

PMID- 28739712
TI  - Total Glossectomy Without Laryngectomy for Advanced Squamous Cell Cancer of the
      Tongue: Functional and Oncological Results.
AB  - BACKGROUND/AIM: Total glossectomy without laryngectomy for large tongue
      carcinomas still remains controversial, as these defects may go along with
      dramatic effects on respiration, speech and swallowing. As a consequence, these
      procedures significantly impact quality of life. Therefore, larger case series
      are rare. Nevertheless, with the development of free tissue transfer, functional
      reconstruction has become increasingly popular and encouraging results are
      reported in the literature. PATIENTS AND METHODS: We present our experience with
      complete glossectomy without laryngectomy and free flap reconstruction. A
      retrospective monocenter cohort-study was conducted. Reconstructive principles,
      which in our view lead to optimal functional results, are presented. Oncologic,
      as well as functional results are reported. Functional results were assessed in
      terms of swallowing ability, decannulation and intelligible speech. RESULTS: A
      total of 14 patients met the inclusion criteria. All patients were reconstructed
      using an anterolateral thigh flap. Complications occurred in 4 patients, 3 of
      which developed fistula formation. Oral feeding without the need for a
      gastrostomy tube was resumed in 11 patients (78.6%), 12 patients (85.7%) were
      able to be permanently decannulated and speech was at least acceptable in 12
      patients (85.7%). The three-year survival was 57.1%. CONCLUSION: Following
      meticulous reconstructive principles, as well as a proper patient selection,
      total glossectomy without laryngectomy is a feasible treatment option for
      advanced cancer of the tongue.

PMID- 28739713
TI  - Feasibility of Postoperative Radiotherapy Using Conventional Fractionation for
      Lymph Node Metastasis from Cutaneous Melanoma.
AB  - AIM: In the present study we assessed if postoperative radiotherapy (PORT) using
      conventional fractionation confers a benefit in cutaneous melanoma patients with
      lymph node (LN) metastasis. PATIENTS AND METHODS: Sixty-two patients with
      axillary or inguinal LN metastasis were retrospectively reviewed. Twenty-eight
      patients received PORT. The median RT dose was 50 Gy in 25 fractions. The high
      risk group was defined by the presence of any of the following: >=3 LNs, size >=3
      cm, extranodal extension. RESULTS: The median follow-up time was 34 months. PORT
      showed a significant benefit on 5-year axilla-inguinal recurrence-free survival
      (RFS) in high-risk patients (RT 100% vs. No-RT 37%, p=0.001). There was also a
      benefit of RT on 5-year out-field RFS in the high-risk population (RT 93% vs. No
      RT 29%, p=0.002). There were no >=grade 2 lymphedemas after RT. CONCLUSION: PORT
      using conventional fractionation for high-risk LN metastasis from cutaneous
      melanoma is feasible with comparable regional control and minimal toxicity.

PMID- 28739716
TI  - Clinical Significance of PD1 and PDL1 in Human Breast Cancer.
AB  - BACKGROUND/AIM: Programmed death 1 (PD1) and its ligand programmed death ligand 1
      (PDL1) form a pathway which when activated is thought to result in suppression of
      antitumor adaptive responses, influencing antitumor immunity. With potential
      targeted therapies emerging against PDL1, we investigated the clinical
      significance of mRNA expression levels of PD1 and PDL1 in our breast cancer
      cohort to explore its association with disease progression and prognosis.
      Previous studies evaluating the expression of PD1 and PDL1 (mRNA or protein) and
      its association with prognosis in breast cancer showed both positive and negative
      correlations and hence remain controversial. MATERIALS AND METHODS: Quantitative
      polymerase chain reaction was used to determine transcript expression levels of
      PD1 and PDL1 in a cohort consisting of primary breast cancer tissues (n=127) and
      matching non-neoplastic background tissues (n=33) with available clinical and
      pathological information. Two-sample two-tailed t-test, Kaplan-Meier survival
      analysis and Wilcoxon tests were performed. RESULTS: Significant PDL1 transcript
      level reductions were seen in patients who developed metastases, as well as those
      who had local recurrence, compared to patients who remained disease-free. Higher
      PDL1 transcript levels were also associated with better overall and disease-free
      survival. Significantly higher transcript expression levels of PD1 were found in
      tumor tissue, whilst a general increase in PDL1 expression was found in tumor
      tissues, although this did not reach statistical significance. CONCLUSION: Our
      study demonstrates higher levels of expression of PDL1 are associated with
      favorable clinical outcome.

PMID- 28739717
TI  - Potential Implication of Paxillin in Cancer Establishment Within the Bone
      Environment.
AB  - BACKGROUND: Bone metastases are a common feature of advanced prostatic
      malignancies. They are characterised by a unique prevalence of osteoblastic
      phenotype and a poor prognosis. Paxillin is a 68-kDa signal transduction adaptor
      and scaffold protein that contains motifs involved in the mediation of protein
      protein interactions. The state of paxillin phosphorylation is central to
      determining a cell's ability to adhere, detach and migrate and hence has been
      linked to processes such as wound repair and tumour metastasis. The current study
      explored the impact of paxillin suppression on prostate and breast cancer cell
      function and their responsiveness to hepatocyte growth factor (HGF) and bone
      matrix extract (BME) in order to assess its potential to influence bone
      colonization and homing. MATERIALS AND METHODS: Hammerhead ribozyme transgenes
      were used to knockdown the expression of paxillin in breast and prostate cancer
      cell lines. The impact on the cell growth, migration, adhesion and invasion was
      assessed using in vitro functional assays. In order to explore potential
      mechanisms, focal adhesion kinase (FAK) inhibitor was also used. RESULTS:
      Knockdown of paxillin expression was observed in all tested cell lines following
      transfection with the ribozyme transgene. The knockdown of paxillin increased
      proliferation and invasiveness of LNCaP cells, with no effect on their attachment
      abilities. The opposite, however, is true for PC-3 cells where, following
      knockdown, cellular attachment was significantly reduced, while no significant
      changes in growth and invasiveness were detected. In the MDA-MB-231 breast cancer
      knockdown model, cells had little difference in proliferative rates and generally
      increased attachment and reduced invasive abilities. Treatments with HGF and BME
      had differential effects on targeted cells when compared to controls. CONCLUSION:
      These data suggest that paxillin appears to influence major cell functions in a
      diverse range of prostate and breast cancer models. The responsiveness of cells
      to environmental factors such as HGF or BME may be influenced by paxillin status,
      although this seems to be dependent on cell type.

PMID- 28739718
TI  - Protein of Vascular Endothelial Growth Inhibitor 174 Inhibits Epithelial
      Mesenchymal Transition in Renal Cell Carcinoma In Vivo.
AB  - BACKGROUND: Vascular endothelial growth inhibitor (VEGI) is a member of the tumor
      necrosis factor superfamily, identified as an anti-angiogenic cytokine. However,
      the effect of VEGI on epithelial-mesenchymal transition (EMT) in renal cell
      carcinoma (RCC) is still unknown. MATERIALS AND METHODS: In this study, protein
      VEGI174 was designed and synthesized. Renal cell carcinoma A498 cells were
      implanted into immune-deficient mice to establish tumor models. Two groups were
      included: control group treated with saline, and VEGI174-treated group. Data of
      tumor growth were collected every 3 to 4 days. Two weeks later, the tumor
      specimens were harvested for immunohistochemical staining of EMT markers (E
      cadherin, N-cadherin, vimentin). RESULTS: Compared to the saline-treated group,
      the VEGI174-treated group showed significant inhibition of tumor growth (p<0.05).
      The expression of E-cadherin was significantly higher in the VEGI174-treated
      group compared to the saline-treated group (p<0.01). However, the expression of N
      cadherin and vimentin were reduced in the VEGI174-treated group. CONCLUSION: Our
      findings indicate that VEGI174 prevents progression and tumor metastasis through
      inhibiting EMT in RCC in vivo. This may provide a new approach for the treatment
      of RCC.

PMID- 28739719
TI  - Expression of Osteoprotegrin Is Enhanced in Lung Cancer Tissues and Promotes
      Aggressive Cellular Traits in H3122 Lung Cancer Cells.
AB  - BACKGROUND: Osteoprotegrin (OPG), a secreted protein and a member of the tumor
      necrosis factor receptor superfamily has been well-characterized and is an
      important regulator of bone remodeling by blocking osteoclast maturation thus
      preventing osteolysis. In recent years, OPG has been reported to have an
      association with the malignant capacity of various cancer types and cancer
      associated bone metastasis, although the mechanisms of this are not clearly
      understood. MATERIALS AND METHODS: In this study, OPG expression was analyzed in
      human lung cancer tissue and normal tissue based on the dataset of The Cancer
      Genome Atlas and Oncomine. The in vitro effect of OPG on H3122 lung cancer cells
      was also assessed by characterizing cell function following knock-down and forced
      overexpression in this cell line. RESULTS: The expression of OPG was
      significantly increased in lung cancer tissues compared to the normal control
      group and OPG promoted the malignant phenotypes of H3122 cells in in vitro
      models. CONCLUSION: OPG may be a potential driver of lung cancer cells and
      therefore might have potential in therapy and diagnostics.

PMID- 28739720
TI  - Inhibition of Bevacizumab-induced Epithelial-Mesenchymal Transition by BATF2
      Overexpression Involves the Suppression of Wnt/beta-Catenin Signaling in
      Glioblastoma Cells.
AB  - BACKGROUND/AIM: Bevacizumab (BV) has been used for the treatment of recurrent
      glioblastoma. However, it also induces epithelial-mesenchymal transition (EMT) in
      glioblastoma cells, which compromises its efficacy. BATF2 (basic leucine zipper
      ATF-like transcription factor 2), a multi-target transcriptional repressor, has
      been found to suppress cancer development partly through inhibition of Wnt/beta
      catenin singling. The roles of BATF2 and Wnt/beta-catenin signaling in BV-induced
      EMT in glioblastoma cells were investigated in this study. MATERIALS AND METHODS:
      BV was used to treat U87MG cells, and TOP/FOP FLASH luciferase reporters were
      employed to determine the activity of Wnt/beta-catenin signaling. EMT markers
      were detected with quantitative reverse transcription-PCR and western blotting.
      Immunofluorescence (IF) was used to determine the compartmentation of beta
      catenin. Wound-healing, TransWell and ECIS assays were used to analyze cell
      adhesion, invasion and migration. RESULTS: BV induced EMT phenotype in U87MG
      cells, and BATF2 overexpression significantly inhibited BV-induced EMT with
      suppression of Wnt/beta-catenin signaling. CONCLUSION: Our findings expanded the
      understanding of the role of BATF2 in tumors, and also suggested a potential of
      using BATF2 as a therapeutic target to hinder bevacizumab induced EMT in
      glioblastoma.

PMID- 28739721
TI  - A Preclinical Study of Cell-seeded Tubularized Scaffolds Specially Secreting LL37
      for Reconstruction of Long Urethral Defects.
AB  - AIM: We constructed a new artificial, long tubular acellular matrix, seeded with
      autologous progenitor cells transfected with the sequence to produce the
      antibiotic peptide LL37 and another two common seeding cells, which might be
      adopted for patients requiring repair of long segment of the urethra. MATERIALS
      AND METHODS: Autologous endothelial progenitor cells transfected by lentiviral
      vectors expressing antibiotic peptide LL37, as well as urothelial and smooth
      muscle cells from New Zealand white male rabbits, were cultured and seeded onto
      preconfigured acellular collagen-based tubular matrices (3 cm in length).
      Artificial conduits were created again in New Zealand white male rabbits and,
      then, evaluated by immunohistochemistry after 8 weeks. RESULTS: Cell-seeded
      tubularized collagen scaffolds were found to be effective in repairing long
      urethral defects, whereas scaffolds without cells led to poor tissue development
      and structures. CONCLUSION: The artificial tissue engineered tubularized
      scaffolds combined with genetic methods resulted in vascularized autologous
      grafts, which may potentially be used for urethroplasty in patients requiring
      repair of a long segment of the urethra.

PMID- 28739722
TI  - GRP78 Participates in PCA3-regulated Prostate Cancer Progression.
AB  - BACKGROUND/AIM: The human prostate cancer antigen 3 (PCA3) is a long non-coding
      RNA (lncRNA) commonly used as a diagnostic marker for prostate cancer (PCa).
      Herein we investigated the cellular function of PCA3 in PCa and its potential
      mechanism. MATERIALS AND METHODS: PCA3 was overexpressed in a PC3 cell line
      (PC3PCA+) and cell proliferation, migration, invasion and apoptosis were compared
      to those of control cells (PC3NC). Differentially expressed proteins were
      identified by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and
      mass spectrometry. RESULTS: Overexpression of PCA3 significantly increased cell
      proliferation rate, migration and invasion, while inhibited apoptosis in PC3
      cells. Three proteins were found down-regulated and 7 proteins up-regulated in
      PC3PCA+ cells compared to PC3NC cells, including GRP78. Higher GRP78 was also
      found in PCa clinical specimens. CONCLUSION: This study confirmed that in PCa,
      PCA3 plays a pro-cancer role through promoting cell proliferation, migration and
      invasion while inhibiting cell apoptosis. This process might involve the up
      regulation of GRP78.

PMID- 28739723
TI  - Immortalized Cancer-associated Fibroblasts Promote Prostate Cancer
      Carcinogenesis, Proliferation and Invasion.
AB  - BACKGROUND: Cancer-associated fibroblasts (CAFs) are dominant components of the
      prostate cancer (PCa) stroma. However, the contrasting effects of CAFs and
      adjacent normal prostate fibroblasts (NPFs) are still poorly defined. The
      senescence of non-immortalized CAFs after subculture may limit the cell number
      and influence experimental results of in vitro studies. In this study, we
      immortalized CAFs to study their role in PCa carcinogenesis, proliferation, and
      invasion. MATERIALS AND METHODS: We cultured and immortalized CAFs and NPFs, then
      compared their effect on epithelial malignant transformation by using in vitro co
      culture, soft agar assay, and a mouse renal capsule xenograft model. We also
      compared their roles in PCa progression by using in vitro co-culture, cell
      viability assays, invasion assays, and a mouse xenograft model. For the
      mechanistic study, we screened a series of growth factors by using real-time
      polymerase chain reaction. RESULTS: The CAFs and NPFs were successfully cultured,
      immortalized, and characterized. The CAFs were able to transform prostate
      epithelial cells into malignant cells, but NPFs were not. The CAFs were more
      active in promoting proliferation of and invasion by PCa cells, and in secreting
      higher levels of a series of growth factors. CONCLUSION: The immortalized CAFs
      were more supportive of PCa carcinogenesis and progression. Targeting CAFs might
      be a potential option for PCa therapy. Immortalized CAFs and NPFs will also be
      valuable resources for future experimental exploration.

PMID- 28739724
TI  - Therapeutic Role of MiR-140-5p for the Treatment of Non-small Cell Lung Cancer.
AB  - BACKGROUND/AIM: Lung cancer is the second most common cancer in both men and
      women, after prostate and breast cancer, respectively. There are two main types
      of primary lung cancer, non-small cell lung cancer (NSCLC), which accounts for
      approximately 85-90% of all lung cancer cases, and small cell lung cancer (SCLC),
      which accounts for the other 10-15% of lung cancers. MiRNAs are small molecules
      that post-transcriptionally regulate many genes and contribute to many disease
      aetiologies, including tumours. In lung cancer, the down-regulation of miR-140-5p
      leads to disease progression. MATERIALS AND METHODS: In this study a miR-140-5p
      only treatment and miR-140-5p combined with other chemotherapeutics have been
      studied in vitro. RESULTS: When transfected into NSCLC, the overexpression of miR
      140-5p reduced the migration and invasion properties of malignant cells and, also
      improved their adhesion onto the artificial extracellular matrix. When miRNA-140
      5p replacement treatment was combined with other drugs commonly used in clinical
      practice, such as gefinitib, DMH1 and cisplatin, it enhanced their efficacy by
      reducing the migration and invasion ability of cancer cells, thus suggesting that
      it acts synergistically with known compounds for the treatment of NSCLC.
      Additionally, some endothelial mesenchymal transition (EMT) markers appeared to
      be regulated by miR-140-5p. CONCLUSION: Novel direct targets of miR-140-5p have
      not been investigated in this study, but our results indicate the involvement of
      miR-140-5p in lung cancer invasion. The preliminary data from this study imply
      that when miR-140-5p levels are restored; maybe synergistically support current
      therapies for NSCLC though further validation, especially in vivo is required.

PMID- 28739725
TI  - High-efficient Screening Method for Identification of Key Genes in Breast Cancer
      Through Microarray and Bioinformatics.
AB  - BACKGROUND/AIM: The aim of the present study was to identify key pathways and
      genes in breast cancer and develop a new method for screening key genes with
      abnormal expression based on bioinformatics. MATERIALS AND METHODS: Three
      microarray datasets GSE21422, GSE42568 and GSE45827 were downloaded from the Gene
      Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were
      analyzed using GEO2R. The gene ontology (GO) and pathway enrichment analysis were
      established through DAVID database. The protein-protein interaction (PPI) network
      was performed through the Search Tool for the Retrieval of Interacting Genes
      (STRING) database and managed by Cytoscape. The overall survival (OS) analysis of
      the 4 genes including AURKA, CDH1, CDK1 and PPARG that had higher degrees in this
      network was uncovered Kaplan-Meier analysis. RESULTS: A total of 811 DEGs were
      identified in breast cancer, which were enriched in biological processes,
      including cell cycle, mitosis, vessel development and lipid metabolic. Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the up
      regulated DEGs were particularly involved in cell cycle, progesterone-mediated
      oocyte maturation and leukocyte transendothelial migration, while the down
      regulated DEGs were mainly involved in regulation of lipolysis, fatty acid
      degradation and glycerolipid metabolism. Through PPI network analysis, 14 hub
      genes were identified. Among them, the high expression of AURKA, CDH1 and CDK1
      were associated with worse OS of breast cancer patients; while the high
      expression of PPARG was linked with better OS. CONCLUSION: The present study
      identified key pathways and genes involved in breast cancer which are potential
      molecular targets for breast cancer treatment and diagnosis.

PMID- 28739726
TI  - HIF1alpha-associated circDENND4C Promotes Proliferation of Breast Cancer Cells in
      Hypoxic Environment.
AB  - BACKGROUND: Accumulating evidence has shown that hypoxia plays a key role in
      regulating proliferation of breast cancer cells. However, the mechanism of how
      hypoxia regulates breast cancer remains unclear. We sought to investigate if
      hypoxia regulated proliferation through circular RNA. MATERIALS AND METHODS:
      Western blot was used to detect hypoxia-inducible factor 1 alpha (HIF1alpha)
      levels in breast cancer cells under hypoxic conditions. Candidate circular RNAs
      (circRNAs) were selected and quantified by quantitative real-time polymerase
      chain reaction (qRT-PCR) after hypoxia induction. CCK8 assay was used to
      investigate the changes of proliferation after interfering circDENND4C and HIF1a.
      RESULTS: In breast cancer cells, circDENND4C was increased under hypoxic
      conditions and decreased after knocking-down HIF1alpha. In addition, knocking
      down circDENND4C inhibited proliferation of breast cancer cells in a hypoxic
      environment. Finally, tumors with a large size had higher circDENND4C expression
      levels than those of small size. CONCLUSION: CircDENND4C is a HIF1alpha
      associated circRNA promoting the proliferation of breast cancer cells under
      hypoxia.

PMID- 28739727
TI  - miR-141 Inhibits Proliferation and Migration of Colorectal Cancer SW480 Cells.
AB  - BACKGROUND: This study was designed to determine the molecular function of miR
      141 and the underlying mechanisms in colorectal cancer (CRC). MATERIALS AND
      METHODS: SW480 cells in which miR-141 was up- or down-regulated were established.
      Reverse transcription, quantitative polymerase chain reaction and Western
      blotting were used to examine the microRNA and protein expression. Cell-cycle
      progression was analyzed by flow cytometry. Proliferation marker Ki-67 was
      evaluated by immunofluorescence. Transwell assay was conducted to determine the
      migration rates of cells. Subcutaneous xenograft models were used to examine the
      effect of miR-141 on tumorigenicity. Human mitogen-activated protein kinase
      (MAPK) and receptor tyrosine kinase (RTK) pathway phosphorylation array assays
      were used to interrogate MAPK and RTK pathway activation. RESULTS: miR-141
      directly targeted zinc finger E-box-binding homeobox 1/2 (ZEB1/2). We first
      determined the expression levels of ZEB1 and ZEB2 in miR-141-expressing cells and
      miR-141-knockdown cells and found that inhibition of miR-141 significantly
      increased the expression of ZEB2. In vitro study revealed that miR-141
      overexpression inhibited the expression of Ki-67. Furthermore, overexpression of
      miR-141 led to a significant reduction in the proliferation of SW480 cells via
      induction of cell-cycle arrest at the G1 stage. In contrast, inhibition of miR
      141 markedly promoted the proliferation of SW480 cells by promoting cell-cycle
      progression. Moreover, overexpression of miR-141 significantly inhibited SW480
      cell migration in vitro. In addition, overexpression of miR-141 significantly
      reduced tumor size and weight, and inhibited the growth of SW480 cell-derived
      tumor in nude mice. Notably, overexpression of miR-141 also suppressed the liver
      metastasis of SW480 cells in nude mice. Using RTK and MAPK arrays, we found
      increased phosphorylation of hepatocyte growth factor receptor (HGFR/c-MET)
      following inhibition of miR-141, but phosphorylation of P53, AKT, ERK1/2, P38 and
      mTOR, etc., in SW480 cells was not affected by miR-141. CONCLUSION: Our results
      suggest that miR-141 functions as a tumor suppressor through ZEB2 and HGFR in CRC
      cells.

PMID- 28739728
TI  - Ezrin-Radixin-Moesin Binding Phosphoprotein 50 (EBP50) Suppresses the Metastasis
      of Breast Cancer and HeLa Cells by Inhibiting Matrix Metalloproteinase-2
      Activity.
AB  - BACKGROUND: Expression of ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50)
      is correlated with human breast and cervical cancer development, but its effects
      on the metastasis of breast and cervical cancer and the underlying mechanism are
      not fully understood. MATERIALS AND METHODS: In this study, EBP50 was
      overexpressed in MDA-MB-231 breast cancer and HeLa cervical cancer cells;
      moreover, EBP50 was knocked-down in MCF-7 breast cancer cells and HeLa cells.
      Metastasis-related ability and matrix metalloproteinase-2 (MMP-2) activity of
      these cells were investigated. RESULTS: Cell adhesion, wound-healing and invasion
      were significantly suppressed in EBP50-overexpressing cells. Contrarily, EBP50
      knockdown promoted cell adhesion, wound healing and invasion. EBP50
      overexpression inhibited MMP-2 activity, and the knockdown of EBP50 promoted the
      activity of MMP-2, suggesting that EBP50 inhibited cell metastasis via
      suppression of MMP-2 activity. CONCLUSION: Our work reveals the anti-metastatic
      effect and a new mechanism of EBP50 action in breast and cervical cancer cells.

PMID- 28739729
TI  - The Axis of CXCR4/SDF-1 Plays a Role in Colon Cancer Cell Adhesion Through
      Regulation of the AKT and IGF1R Signalling Pathways.
AB  - BACKGROUND/AIM: Colorectal cancer (CRC) is the third most common cancer in the
      world. The high mortality of this tumor is mainly due to its invasive properties,
      as it forms metastases in multiple organs, preferentially in the liver. There has
      evidence showing that C-X-C chemokine receptor type 4 (CXCR-4) and its ligand,
      stromal cell-derived factor-1 (SDF-1), plays an important role in cancer
      progression and metastasis. However, the molecular mechanism underling the CRCR4
      mediated CRC metastasis has not been well characterized. In this study, we aimed
      to investigate the roles of CXCR4 in colorectal cancer using the clustered
      regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated
      protein 9 (Cas9)-based genomic editing technique. MATERIALS AND METHODS: We
      knocked-down CXCR4 using specific guide-RNA linked CRISPR/Cas9 in HT115 and
      COLO201 colon cancer cell lines which exhibited high levels of endogenous CXCR4
      gene expression. Stable HT115 cells with CXCR4 knock-down were established by
      CRISPR plasmid transfection and validation was confirmed using T7 endonuclease 1
      (T7EN1), flow cytometry (FACS) and western blotting assays. RESULTS: Knock-down
      of CXCR4 did not decrease proliferation of HT115 cells, but decreased the
      adhesion potential of cells to the human umbilical vein endothelial cells (HUVEC)
      and extracellular matrix. We further demonstrated that the AKT and type 1 insulin
      like growth factor receptor (IGF1R) signalling pathways may be involved in the
      alteration of adhesion in CRC cells when CXCR4 is knocked down. CONCLUSION: Our
      data suggest that CXCR4 plays a key role in colorectal cancer progression via the
      mediation of tumor cell adhesion.

PMID- 28739730
TI  - Comparison of Different Muscle-Relaxant Anesthetics on Growth, Migration and
      Invasion of Gastric Cancer Cells.
AB  - BACKGROUND/AIM: Muscle relaxants, also known as neuromuscular blocking agents,
      can block nerve impulses to the muscles and are always used in surgery for
      general anesthesia. However, the effect of muscle-relaxant anesthetics on cell
      activity in gastric cancer is currently unknown. The present study aimed to
      examine and compare the role of three different muscle-relaxant anesthetics in
      gastric cancer cells. MATERIALS AND METHODS: Gastric cancer cells (SGC7901 and
      BGC 823) were treated with a different dose of muscle-relaxant anesthetics,
      Rocuronium bromide (Rb), Vecuronium bromide (Vb) and Cisatracurium Besilate (CB).
      Using in vitro models, the effects on gastric cancer cell invasion, growth and
      migration of various anesthetics were subsequently investigated. RESULTS: We
      found that Rb increased the growth, invasion and migration of gastric cancer
      cells SGC7901 and BGC823. However, Vb and CB, as relatively mitigative
      anesthetics, did not significantly affect gastric cancer cell malignant phenotype
      at their regular blood concentration. CONCLUSION: Our results are important in
      selecting the type and dose of anesthetic used for surgery of gastric cancer
      patients. An understanding of the effect of muscle-relaxant anesthetics and their
      impact on tumor metastasis is critical, since it provides insight into the
      appropriate anesthetic strategy that could improve long-term survival in some
      patients with gastric cancer.

PMID- 28739731
TI  - Identification of Novel Proteins Interacting with Vascular Endothelial Growth
      Inhibitor 174 in Renal Cell Carcinoma.
AB  - BACKGROUND/AIM: Vascular endothelial growth inhibitor (VEGI) is a multipotential
      cytokine that plays a role in regulating immunity, anti-angiogenesis, and
      inhibiting tumor growth. However, the proteins that interact with it are still
      unknown. In the present study, we examined the proteins that interact with
      VEGI174 and their expression in renal cell carcinoma (RCC). MATERIALS AND
      METHODS: The proteins that interact with VEGI174 were identified using western
      blot, pull-down assay, and mass spectrometry. The expressions of VEGI174 and the
      interacting proteins were examined in RCC and were compared to normal renal
      tissues using immunohistochemical staining and RNA-seq respectively. RESULTS: The
      results of the mass spectrometric analysis showed that ACLY, ENO1, ZIK1, AKR1C3,
      and MYC may interact with VEGI174. When compared to the TCGA database, the
      expression level of VEGI174 in RCC was lower than that in normal kidney using
      RNAseq (p<0.001). The expression levels of ACLY, ENO1, ZIK1, AKR1C3 and MYC in
      RCC were higher than those in normal kidney (p<0.05, all of above factors).
      Moreover, immunochemical staining results also showed that the expression levels
      of AKR1C3 in RCC were significantly higher those that in normal kidney (p<0.001)
      and was also positively correlated with higher RCC stage and grade. CONCLUSION:
      Taken together, our findings showed that VEGI174 may interact with ACLY, ENO1,
      ZIK1, AKR1C3, and MYC. The expression of ACLY, ENO1, AKR1C3 and MYC is increased
      in RCC. AKR1C3 was a new factor that may correlate with the progression of RCC.
      The results indicated that VEGI174 has more functions than we currently know in
      the development and progression of RCC.

PMID- 28739732
TI  - Reduced Expression of RanBPM Is Associated with Poorer Survival from Lung Cancer
      and Increased Proliferation and Invasion of Lung Cancer Cells In Vitro.
AB  - BACKGROUND/AIM: Ran binding protein microtubule-organizing centre (RanBPM), also
      known as RanBP9, is a scaffold protein conserved through evolution. We
      investigated the role of RanBPM in human lung cancer. MATERIALS AND METHODS:
      Transcripts of RanBPM were determined in 56 human lung cancers along with paired
      normal lung tissues using real-time PCR. Association with prognosis was analyzed
      by online Kaplan-Meier survival analysis. In vitro lung cancer cell functional
      assays examined the impact of RanBPM-knockdown on cellular growth and invasion.
      RESULTS: Higher expression of RanBPM was observed in tumor when compared to
      paired normal lung tissues. Increased RanBPM expression was seen in patients with
      longer overall and disease-free survival. Knockdown of RanBPM in lung cancer cell
      lines resulted in increased growth and invasion in vitro. CONCLUSION: Increased
      expression of RanBPM associates with postponed disease progression and better
      prognosis. RanBPM plays an inhibitory role in regulating proliferation and
      invasion of lung cancer cells.

PMID- 28739733
TI  - Analysis of Association Between MGMT and p53 Gene Single Nucleotide Polymorphisms
      and Laryngeal Cancer.
AB  - AIM: To investigate the p53 and O6-methylguanine DNA methyltransferase (MGMT)5'
      upstream sequence gene promoter regions for single nucleotide polymorphisms and
      explore the p53 gene 5' upstream sequence consisting of two haplotypes to provide
      a genetic marker for the incidence of laryngeal squamous cell carcinoma.
      MATERIALS AND METHODS: We included 96 cases of laryngeal squamous cell carcinoma
      and 102 controls. We used SNaPshot micro-sequencing analysis of the MGMT promoter
      region for four single nucleotide polymorphisms and p53 gene 5' upstream sequence
      loci (rs1625649, rs2287499, rs2287498, rs228749) genotypes. We calculated and
      compared two groups for genotypic and allelic frequencies, applied HaploView4.2
      for computing rs2287499, rs2287498, rs228749 values and haplotype frequencies and
      tested control loci and Hardy-Weinberg equilibrium. All the experimental data
      were statistically evaluated using SPSS17.0. The Chi-square test was used for
      statistical analysis with p<0.05 indicating statistical significance. RESULTS:
      5'Upstream single nucleotide polymorphisms rs1625649, rs2287499, rs2287498,
      rs228749 of p53 were polymorphic in both patient and control groups. There was no
      statistical significance in frequency distributions for the four loci genotypes
      when comparing patients and healthy controls (Chi-square values were 4.47, 0.98,
      1.67, 4.68, respectively; p>0.05). However, allelic frequencies of the MGMT
      promoter region locus rs1625649 between patients and healthy control groups were
      statistically significantly different (chi-square value of 5.77; p<0.05).
      Differences between allelic frequencies for the p53 gene 5' upstream sequence
      loci rs2287499, rs2287498 and rs228749 between patients and the healthy control
      group were not statistically significant (Chi-square values were 1.11,1.56,3.36;
      p>0.05). Nor were those for the two haplotypes of rs2287499, rs2287498 and
      rs228749 between patients and the healthy control group were not statistically
      significant (Chi-square value 1.46, p>0.05). CONCLUSION: MGMT gene polymorphism
      appears to be associated with the incidence of laryngeal cancer.

PMID- 28739734
TI  - NHERF1 Suppresses Lung Cancer Cell Migration by Regulation of Epithelial
      Mesenchymal Transition.
AB  - BACKGROUND/AIM: Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) has been
      reported to interact with many cancer-related proteins and plays an important
      role in cancer progression. However, little is known about the biological
      functions of NHERF1 in lung cancer cells. The aim of the current study was to
      explore whether NHERF1 is involved in transforming growth factor (TGF)-beta1
      induced epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer
      cells. MATERIALS AND METHODS: The expression of NHERF1 and EMT-associated markers
      including E-cadherin, N-cadherin, snail family transcriptional repressor 1
      (SNAI1) and snail family transcriptional repressor 2 (SLUG) were analyzed by
      reverse transcription polymerase chain reaction (RT-PCR) and western blotting.
      The migratory properties of cells were assessed using a wound-healing assay.
      RESULTS: TGF-beta1-induced a pro-migratory response in the A549 lung cancer cell
      line, that was consistently associated with corresponding changes in the
      expression levels of EMT-related genes. The expression of NHERF1 significantly
      decreased in the TGF-beta1-induced A549 cells. Overexpression of NHERF1
      significantly inhibited the migratory ability of cells and reversed the TGF-beta1
      induced mesenchymal phenotype of A549 cells. CONCLUSION: These data showed an
      important role of NHERF1 in the EMT of non-small-cell lung cancer cells, as well
      as migration.

PMID- 28739735
TI  - Knockdown of EPHA1 Using CRISPR/CAS9 Suppresses Aggressive Properties of Ovarian
      Cancer Cells.
AB  - BACKGROUND/AIM: Overexpression of erythropoietin-producing hepatocellular A1
      (EPHA1), a member of the EPH super family, is frequently observed in various
      cancer types. The dysregulated interaction of EPHA1 with its ligand Ephrin A1 has
      been linked to the progression of ovarian cancer (OC). However, the contribution
      of EPHA1 in the regulation of the aggressive properties of OC cells remains
      unknown. MATERIALS AND METHODS: In this study we investigated the differential
      expression of EPHA1 in human OC cells. The EPHA1 gene was knocked-down using the
      CRISPR/Cas9 technique to evaluate its effect on the progressive properties of OC
      cells. RESULTS: After EPHA1 was knocked-down using a CRISPR/CAS9 genomic editing
      system in OC cells (SKOV3 and COV504), we observed cell-cycle arrest at the G0/G1
      phases in both OC cell lines. Knockdown of EPHA1 in the two OC cells inhibited
      their aggressive traits, including proliferation, invasion and migration, as well
      as improving their attachment to extracellular matrix. EPHA1 may play a role in
      OC through its regulation of multiple signaling pathways, such as matrix
      metalloproteinase-2 (MMP2), extracellular signal-regulated kinase 2 (ERK2) and
      proto-oncogene c-MYC. CONCLUSION: EPHA1 may promote the aggression of some OC
      cells and, thus, be considered a potential therapeutic target for the treatment
      of malignant OC.

PMID- 28739736
TI  - Puerarin Induces Hepatocellular Carcinoma Cell Apoptosis Modulated by MAPK
      Signaling Pathways in a Dose-dependent Manner.
AB  - BACKGROUND/AIM: Puerarin possesses a battery of therapeutic values in diverse
      disorders, including pro-apoptotic actions in multiple cancers. Herein, we
      investigated the effects of puerarin on hepatocellular carcinoma (HCC) in vitro.
      MATERIALS AND METHODS: MTT and flow cytometry were carried out to evaluate the
      viability and apoptosis of SMMC-7721 HCC cells in the presence of different
      concentrations of puerarin. Moreover, expression levels, as well as
      phosphorylation status of several canonical components in mitogen-activated
      protein kinase (MAPK) pathways, including extracellular signal-regulated kinase
      1/2 (ERK1/2), c- Jun N-terminal kinase (JNK), p38, were measured by reverse
      transcription and quantitative real-time polymerase chain reaction (RT-PCR) and
      western blot analysis at indicated time intervals. RESULTS: Puerarin inhibited
      proliferation of SMMC-7721 cells and promoted their apoptosis in a dose- and time
      dependent fashion (p<0.05). Both the expression and phosphorylation levels of
      MAPK proteins were dramatically increased on puerarin treatment. CONCLUSION:
      Puerarin could be employed as a potential anti-carcinogen that exhibits pro
      apoptotic effects on HCC cells, in a dose- and time-dependent manner, with
      emphasis on MAPK pathways whose initiation may contribute to this process.

PMID- 28739737
TI  - Synergistic Effects of SAM and Selenium Compounds on Proliferation, Migration and
      Adhesion of HeLa Cells.
AB  - BACKGROUND/AIM: To determine the antitumor activities and molecular mechanism of
      selenium compounds in HeLa cells. MATERIALS AND METHODS: Western blotting was
      used to detect ERK and AKT activation in HeLa cells induced by selenium compounds
      selenomethionine (SeMet), methylselenocysteine (MeSeCys) and methylseleninic
      acids (MeSeA). Using MTT, wound-healing and Matrigel adhesion assays, the
      antitumor effects of SAM and selenium compounds were evaluated in HeLa cells.
      RESULTS: MeSeA inhibited ERK and AKT signaling pathways and suppressed the
      proliferation (p<0.05 vs. HeLa control), migration (p<0.05 vs. HeLa control) and
      adhesion (p<0.01 vs. HeLa control) of HeLa cells. MeSeCys and SeMet inhibited AKT
      signaling pathways and the migration (p<0.05 vs. HeLa control) and adhesion
      (p<0.01 vs. HeLa control) of HeLa cells. The synergistic action of MeSeA with SAM
      led to a statistically significant inhibition of proliferation, migration and
      adhesion of HeLa cells. CONCLUSION: MeSeA, MeSeCys and SeMet exert different
      antitumor activities by inhibiting ERK and AKT signaling pathways. The
      combination of MeSeA and SAM exhibited better antitumor effects compared to the
      other treatments.

PMID- 28739738
TI  - Cyclophilin A Is Overexpressed in Hepatocellular Carcinoma and Is Associated with
      the Cell Cycle.
AB  - AIM: To investigate the expression of cyclophilin A (CypA) in human
      hepatocellular carcinoma (HCC) and explore the effects of CypA on the cell cycle
      in HCC. MATERIALS AND METHODS: CypA expression was assessed by
      immunohistochemistry in 48 cases of HCC tissues and paired adjacent tissues. CypA
      plasmid was transfected into HCC cells and the cell cycle was analyzed. RESULTS:
      Positivity for CypA was higher in HCC tissues than in adjacent tissues (79.1% vs.
      12.5%, p<0.05). Positivity for CypA was significantly higher in stage III and IV
      HCC than in stage I and II (p<0.05). Elevated CypA induced an increase of the
      percentage of S-phase cells (from 34.79% to 42.14%) and a decrease of G0-G1 phase
      cells (from 58.10% to 50.64%). CONCLUSION: CypA is overexpressed in HCC and is
      associated with TNM stage. CypA also appears to promote the transition of the
      cell cycle from G1 to S phase.

PMID- 28739739
TI  - Transcriptional Profiling of Sonic Hedgehog in a Prospective Cohort of Breast
      Cancer in a Pakistani Population.
AB  - BACKGROUND/AIM: Constitutive activation of Sonic hedgehog (SHH) has been observed
      in different types of cancers. In the present study, expressional profiling of
      SHH in a breast cancer cohort (n=150) of a Pakistani population and its
      association with different molecular subtypes have been explored. MATERIALS AND
      METHODS: qRT-PCR and IHC were performed for expression analysis of SHH and its
      association with ER, PR, HER2 and Ki-67 were also statistically analyzed.
      RESULTS: A significant over-expression of SHH was observed in tumor tissues in
      comparison to their respective controls (p<0.0001). A strong positive correlation
      was seen between SHH and proliferation marker (r=0.635, p=0). SHH expression was
      significantly high among patients with advanced tumor grade, stage, nodal
      involvement and metastasis. Furthermore, both luminal-B and triple-negative
      subtypes of cohort showed increased expression of SHH. CONCLUSION: Based on these
      findings, SHH may be used as a potential biomarker for breast carcinogenesis.

PMID- 28739740
TI  - Global Analysis of miRNA-mRNA Interaction Network in Breast Cancer with Brain
      Metastasis.
AB  - BACKGROUND: MicroRNAs (miRNAs) have been linked to a number of cancer types
      including breast cancer. The rate of brain metastases is 10-30% in patients with
      advanced breast cancer which is associated with poor prognosis. The potential
      application of miRNAs in the diagnostics and therapeutics of breast cancer with
      brain metastasis is an area of intense interest. In an initial effort to
      systematically address the differential expression of miRNAs and mRNAs in primary
      breast cancer which may provide clues for early detection of brain metastasis, we
      analyzed the consequent changes in global patterns of gene expression in Gene
      Expression Omnibus (GEO) data set obtained by microarray from patients with in
      situ carcinoma and patients with brain metastasis. MATERIALS AND METHODS: The
      miRNA-pathway regulatory network and miRNA-mRNA regulatory network were
      investigated in breast cancer specimens from patients with brain metastasis to
      screen for significantly dysregulated miRNAs followed by prediction of their
      target genes and pathways by Gene Ontology (GO) analysis. RESULTS: Functional
      coordination of the changes of gene expression can be modulated by individual
      miRNAs. Two miRNAs, hsa-miR-17-5p and hsa-miR-16-5p, were identified as having
      the highest associations with targeted mRNAs [such as B-cell lymphoma 2 (BCL2),
      small body size/mothers against decapentaplegic 3 (SMAD3) and suppressor of
      cytokine signaling 1 (SOCS1)] and pathways associated with epithelial-mesenchymal
      transitions and other processes linked with cancer metastasis (including cell
      cycle, adherence junctions and extracellular matrix-receptor interaction). mRNAs
      for two genes [HECT, UBA and WWE domain containing 1 (HUWE1) and BCL2] were found
      to have the highest associations with miRNAs, which were down-regulated in brain
      metastasis specimens of breast cancer. The change of 11 selected miRNAs was
      verified in The Cancer Genome Atlas (TCGA) breast cancer dataset. Up-regulation
      of hsa-miR-17-5p was detected in triple-negative breast cancer tissues in TCGA.
      Furthermore, a negative correlation of hsa-miR-17-5p with overall survival and
      phosphatase and tensin homolog (PTEN) and BCL2 target genes was found in TCGA
      breast cancer specimens. CONCLUSION: Our findings provide a functionally
      coordinated expression pattern of different families of miRNAs that may have
      potential to provide clinicians with a strategy to treat breast cancer with brain
      metastasis from a systems-rather than a single-gene perspective.

PMID- 28739741
TI  - Clinical Correlation Between WISP2 and beta-Catenin in Gastric Cancer.
AB  - BACKGROUND: Evidence indicates that wingless-type MMTV integration site family,
      member 1 (WNT1)-inducible signaling pathway protein 2 (WISP2) may play an
      important role in the development of gastric cancer (GC) by regulating the
      WNT/beta-catenin signaling pathway. In the present study, we investigated whether
      there is correlation between WISP2 and beta-catenin proteins, and their
      association with clinicopathological features in GC. MATERIALS AND METHODS:
      Immunohistochemical staining was carried out on 119 paraffin-embedded gastric
      cancer tissues and 99 adjacent normal gastric tissues collected from patients
      with GC at the Beijing Cancer Hospital. Data were analyzed by Spearman rank
      correlation and Chi-square tests. RESULTS: Both WISP2 and beta-catenin were more
      highly expressed in GC tissues compared to adjacent normal tissues. Moreover,
      Spearman rank correlation analysis showed positive correlation between WISP2 and
      beta-catenin (R=0.2254, p=0.0137). Additionally, their co-expression was seen in
      a higher proportion of patients with GC at early stage or without metastasis.
      CONCLUSION: These findings suggest that the expression of WISP2 and beta-catenin
      might be a favorable biomarker for prediction and prognosis in the early stage of
      GC.

PMID- 28739742
TI  - Expression and Significance of Cyclophilin J in Primary Gastric Adenocarcinoma.
AB  - BACKGROUND/AIM: Biomarkers are essential in early diagnosis and understanding of
      the molecular mechanism of human cancer. The expression of cyclophilin J, a novel
      member of the cyclophilin family, was investigated in primary gastric
      adenocarcinoma. MATERIALS AND METHODS: Western blot analysis was carried out on
      36 paired tumor and normal tissue samples; immunohistochemical analysis was
      carried out on 120 gastric carcinoma tissues and normal adjacent tissue. RESULTS:
      Cyclophilin J protein was overexpressed in 72.2% of gastric carcinoma tissues
      compared to adjacent normal tissues. Immunohistochemical analysis revealed that
      cyclophilin J was overexpressed in 49.2% (59/120) and 23.3% (28/120) of gastric
      carcinoma tissues and adjacent tissues, respectively (p<0.05). Expression of
      cyclophilin J was associated with the degree of differentiation, but not with
      lymph node metastasis, gender or depth of tumor infiltration. The overall
      survival of patients showed no association with the overexpression of cyclophilin
      J protein. CONCLUSION: Cyclophilin J expression was up-regulated in gastric
      carcinoma compared to normal gastric tissues. However, in order to confirm its
      association with the survival of patients with gastric cancer, more cases need to
      be studied.

PMID- 28739743
TI  - Role of Plexin B1 in a Breast Cancer Cohort of Pakistani Patients and its
      Contribution Towards Cancer Metastasis as Indicated by an In Vitro Model.
AB  - BACKGROUND/AIM: In the current study, the role of plexin B1 in breast cancer
      metastasis was explored. MATERIALS AND METHODS: Freshly-excised tumours along
      with background tissues of affected patients (n=121) were collected from
      Pakistani hospitals and processed for RNA isolation and cDNA synthesis. Using
      quantitative polymerase chain reaction, expression of plexin B1 was evaluated and
      correlated with clinicopathological parameters. Furthermore, involvement of
      plexin B1 in metastasis was explored by generating gene knockdown in MDA-MB-231
      and MCF-7 breast cancer cells. RESULTS: Poorly-differentiated tumours showed low
      plexin B1 expression in comparison to well-differentiated ones. Similarly,
      reduced plexin B1 expression correlated positively with advanced tumour stage and
      metastasis. Loss of plexin B1 significantly reduced cell adhesion in comparison
      with respective control cell lines (p<0.05). Knockdown of plexin B1 in MDA-MB-231
      cells led to a remarkable increase in cell motility in contrast to the respective
      control. CONCLUSION: Loss of plexin B1 expression might play a pivotal role in
      enhancing the metastatic potential of breast cancer cells.

PMID- 28739744
TI  - Overexpression of EPHB4 Is Associated with Poor Survival of Patients with Gastric
      Cancer.
AB  - BACKGROUND: Increased expression of erythropoietin-producing human hepatoma
      (EPHB4) leads to enhanced cell migration, growth and adhesion in tumor cells.
      However, little is known regarding the effects of EPHB4 in gastric cancer. The
      present study aimed to examine the clinical relevance of EPHB4 and its
      association with the prognosis of gastric cancer. MATERIALS AND METHODS: EPHB4
      transcript expression in 324 gastric cancer samples with paired adjacent normal
      gastric tissues was determined using quantitative polymerase chain reaction and
      the results were statistically analyzed against patient clinicopathological data.
      AGS and HGC27 cell lines were transfected with EPHB4 siRNA and the effects
      examined by functional analysis. RESULTS: EPHB4 mRNA levels in gastric cancer
      tissues were significantly elevated when compared to non-cancerous tissues
      (p=0.0110). Tissue samples from male patients exhibited lower expression than
      those from female patients (p=0.0110). Non-cardiac gastric tumors (fundus, corpus
      and pylorus) expressed a higher number of EPHB4 transcripts in comparison to
      cardiac gastric tumors (p<0.001). Increased expression of EPHB4 was significantly
      associated with poorer overall (p=0.0051) and progression-free (p=0.0262)
      survival. EPHB4 knockdown appeared to reduce post-wound migration of AGS cells
      (p=0.0057) and increase migration of HGC27 cells (p=0.0337). EPHB4 knockdown
      significantly increased adhesive ability in HGC27 (p<0.0001). CONCLUSION: The
      expression of EPHB4 was increased in gastric cancer and increased EPHB4
      expression was correlated with poor survival. Knockdown of EPHB4 promoted
      adhesion and exerted diverse effects on migration of gastric cancer cells.
      Further investigations may highlight its predictive and therapeutic potential in
      gastric cancer.

PMID- 28739745
TI  - Reduced Expression of Metastasis Suppressor-1 (MTSS1) Accelerates Progression of
      Human Bladder Uroepithelium Cell Carcinoma.
AB  - BACKGROUND: Metastasis suppressor 1 (MTSS1) is a multi-functional cytoskeletal
      protein. Recent research showed that MTSS1 is a potential tumor suppressor in
      many types of cancer cells, including kidney and bladder cancer cells. However,
      the clinical implication of MTSS1 in human bladder uroepithelium cell carcinoma
      (BUCC) and its potential in suppressing BUCC tumorigenesis remains undetermined.
      In the present study, the expression of MTSS1 in human BUCC tissue samples, and
      correlations between MTSS1 and pathological grade and stage of the tumors were
      examined in BUCC specimens. The function of MTSS1 in BUCC progression was
      explored. MATERIALS AND METHODS: The mRNA and protein expression of MTSS1 were
      examined in 68 BUCC tissue samples with matching adjacent normal bladder tissues
      using quantitative real-time PCR and western blotting. Furthermore, the bladder
      cancer cell line 5637 was used to determine the anticancer effect of MTSS1.
      RESULTS: Lower MTSS1 mRNA expression was recorded in BUCC tissues compared to
      normal bladder tissues. A lower MTSS1 mRNA level was observed in tumors with high
      clinical stage and with high pathological nuclear grade. Likewise, MTSS1 protein
      expression in normal bladder tissue was significantly higher than that in BUCC
      tissue. The protein level of MTSS1 significantly negatively correlated with
      clinical stage and pathological nuclear grade of BUCC. Cumulative survival curves
      indicated that MTSS1 expression was negatively correlated with survival time:
      patients with a high level of MTSS1 had significantly longer survival time than
      those with a low level of MTSS1 (p<0.001). Overexpression of MTSS1 reduced BUCC
      cell proliferation, cell-cycle progression and colony formation, but had no
      influence on BUCC cell apoptosis. CONCLUSION: Overexpression of MTSS1 suppresses
      BUCC development, providing a novel perspective for BUCC tumorigenesis and a
      potential therapeutic target for BUCC.

PMID- 28739746
TI  - Association of Intron Microsatellite Instability and Exon Mutational Profile of
      TP53 in Human Gastric Cancers.
AB  - BACKGROUND/AIM: Microsatellite instability (MSI) is a hallmark of genomic
      instability. In gastric cancer (GC), MSI phenotype is an important molecular
      subgroup that is often closely correlated with elevated mutation rates on the
      whole genome level. However, on a single gene level, it is still unknown whether
      the MSI status of a gene is correlated with the mutational profile of the gene
      itself. MATERIALS AND METHODS: We analyzed intron MSI status and exon mutational
      profile of TP53 through short tandem repeat (STR) scanning and direct sequencing
      respectively in gastric cancers and their matched normal tissues. RESULTS: MSI
      status of the TP53 intron was significantly associated with the mutational
      profile of seven TP53 exon positions (p=0.0416), male patients (p=0.0095), and
      drinking (p=0.0474), and showed a mild correlation with longer survival time
      (p=0.0584) and increasing age (p=0.0611). CONCLUSION: TP53 exons tended to
      mutation in the status of TP53 intron MSI.

PMID- 28739747
TI  - Application of Serum ELAVL4 (HuD) Antigen Assay for Small Cell Lung Cancer
      Diagnosis.
AB  - BACKGROUND/AIM: The ELAVL4 (HuD) is a neuron-specific RNA-binding protein
      expressed in 100% of small cell lung cancer (SCLC) cells and over 50% of
      neuroblastoma cells. The aim of this study was to investigate the serum HuD
      concentration in SCLC patients and the possibility of its utilization as a
      biomarker of small cell lung cancer. MATERIALS AND METHODS: Our study included 47
      SCLC cases and 29 normal controls. Indirect competitive inhibition ELISA method
      was established to detect HuD antigen of serum samples. To design the ELISA
      system, purified antigen and real positive and negative serum samples were used,
      and checkerboard titration was performed. The value of current serum biomarkers
      (Pro-GRP, NSE, CYFRA21-1 and CEA) was obtained from a clinical laboratory.
      RESULTS: The HuD antigen concentration in the SCLCgroup was significantly higher
      than that in the normal group (p<0.01). The cut-off value, specificity and
      sensitivity were 60 ng/ml, 89.7% and 74.5%, respectively. The best linear range
      was 9.75~600 ng/ml. The sensitivity of the HuD-ELISA assay was much better than
      the current biomarkers-CEA, NSE and pro-GRP. Also,it was equal to or better than
      the combined use of two or three indicators. CONCLUSION: The high titres of HuD
      in SCLC patients and preferable consistency suggested that HuD may serve as a
      potential diagnostic criterium for SCLC and may serve as a marker of disease
      progression.

PMID- 28739748
TI  - Application of Localization and Needle Placement Guided by Mammographic,
      Ultrasound and Fiberoptic Ductoscopy for Resection of Non-palpable Breast
      Lesions.
AB  - AIM: To evaluate the usefulness of localization needles under mammographic,
      ultrasound or fiberoptic ductoscopy guidance for non-palpable breast lesions.
      PATIENTS AND METHODS: Eighty-three patients undergoing needle localization and
      biopsy of non-palpable breast lesions under mammographic, ultrasound or
      fiberoptic ductoscopy guidance from June 2013 to December 2014 in Beijing
      Friendship Hospital were included in the study. The preoperative imaging
      assessment, application of localization needles, surgical operation and
      pathological examination were recorded and analyzed retrospectively. RESULTS: A
      total of 83 localization and biopsies were carried out, of which 27 were
      performed under mammographic guidance, 32 under ultrasound guidance and 24 under
      fiberoptic ductoscopy guidance. Twenty-seven cases of breast microcalcifications
      were localized under mammographic guidance and surgically removed, of which eight
      cases were pathologically diagnosed as malignant. Thirty-two cases of non
      palpable breast lesions were localized under ultrasound guidance and 30
      pathologically diagnosed, of these, four cases were pathologically diagnosed as
      malignant. Twenty-four cases of intraductal space-occupying lesions were
      localized under ductoscopy guidance and surgically removed, of which five cases
      were pathologically diagnosed as malignant. CONCLUSION: Utilization of
      localization needles under mammographic, ultrasound or fiberoptic ductoscopy
      guidance for non-palpable breast lesions is a safe and effective procedure, and
      is helpful in the diagnosis of breast cancer. With the help of this procedure,
      more malignant lesions can be localized and surgically removed.

PMID- 28739749
TI  - Analysis of Clinicopathological Features and Prognostic Factors in 39 Cases of
      Bladder Neuroendocrine Carcinoma.
AB  - AIM: Through analysis and summarization of clinicopathological features,
      immunohistochemical expression, pathological diagnostic criteria, prognostic and
      other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC),
      a better understanding of BNEC could be achieved to provide solid evidence for
      clinicopathology and prognosis. MATERIALS AND METHODS: The clinicopathological
      data of 39 cases of BNEC with up to 5-year follow-up data (median follow-up=650
      days) were analyzed retrospectively based on immunohistochemical staining.
      Survival analyses were carried out using the Kaplan-Meier method and tested with
      the log-rank method. Multivariate Cox regression analysis was adopted to screen
      independent risk factors affecting patients' survival. In these 39 cases of BNEC,
      there were 26 cases of male patients, 13 female, with the proportion of male to
      female being 2:1. The ages of onset ranged from 44 to 86, with the median age
      being 62 and the average age 61.97 years, respectively. Histologically, referring
      to the WHO standard of neuroendocrine lung tumor classification, there were 7
      cases of typical carcinoid tumors, 8 atypical carcinoid, 12 small-cell carcinomas
      and 12 large-cell carcinomas. In these cases there were 11 cases of featured
      urothelium carcinomas and 9 cases of adenocarcinomas. RESULTS:
      Immunohistochemical staining showed that, in these 39 cases of BNEC, the positive
      expression for the neuroendocrinic markers, including neural cell adhesion
      molecule 56 (CD56), synaptophysin (Syn), chromogranin A (CgA), neuron-specific
      enolase (NSE), thyroid transcription factor-1 (TTF-1), cytokeratin (CK) and
      cytokeratin 7 (CK7), accounted for 39/39, 27/39, 18/39, 39/39, 19/39, 10/39 and
      8/39, respectively. In contrast, cytokeratin 20 (CK20), protein 63 (P63), human
      melanoma black 45 (HMB45), S-lfln protein 100 (S-100) and leukocyte common
      antigen (LCA) were all negatively expressed. During the follow-up period, 12
      patients died. The 1-, 3- and 5-year overall survival (OS) rates were 76.92%,
      74.36% and 69.23%. CONCLUSION: BNEC is one of the most malignant tumors with
      severe invasiveness and poor prognosis. Immunohistochemistry revealed that CD56,
      Syn, CgA, NSE, TTF-1, CK, CK7, CK20, P63, HMB45, S-100 protein and LCA immune
      markers play important roles in diagnosis and differentiation. Many factors,
      including the patient's age, size and shape of the tumor, operative method,
      perineuronal invasion, vascular invasion, distant organ metastasis and
      pathological type, show great difference in influencing OS time of patients,
      among which the size of the tumor, no invasion, vascular invasion and distant
      organ metastasis are independent risk factors affecting prognosis (survival
      time). Radical cystectomy is the prior alternative to treat this tumor.

PMID- 28739750
TI  - Impact of a 21-Gene Recurrence Score Test on the Choice of Adjuvant Chemotherapy
      for Hormone Receptor-positive Early-stage Breast Cancer: A Prospective Study.
AB  - BACKGROUND: Studies have recommended a 21-gene recurrence score (RS) to optimize
      adjuvant treatment for patients with early-stage breast cancer (EBC) with hormone
      receptor-positive (HR+) and human epidermal growth factor receptor-2 negative
      (HER2-) tumors. This study aimed to prospectively evaluate the impact of this RS
      in Chinese patients with breast cancer. PATIENTS AND METHODS: We prospectively
      collected 227 patients with EBC with estrogen receptor-positive (ER+) and HER2-
      tumors. We used one-way analysis of variance to compare the distribution of
      different risk groups based on a 21-gene RS assay. A Kruskal-Wallis test and
      either a chi-square or Fisher's exact test were used as appropriate to compare
      continuous and categorical variables, respectively. RESULTS: Of the 227 eligible
      women enrolled, 61.2%, 30%, and 8.8% of patients were in the low (<=17),
      intermediate (18-30) and high (>=31) RS groups, respectively. Of the patients
      with a low RS, 74.8% were overestimated into the intermediate-risk group by St.
      Gallen risk. The overall impact of the 21-gene RS was reduced use of chemotherapy
      (78/227, 34.4%). In addition, Ki67 expression was positively associated with the
      21-gene RS (R=0.68). CONCLUSION: Among patients with ER+/HER2- EBC, the 21-gene
      RS was an effective method for making a chemotherapy decision. Ki67 was
      associated with 21-gene RS.

PMID- 28739751
TI  - The Clinicopathological Factors Associated with Disease Progression in Luminal A
      Breast Cancer and Characteristics of Metastasis: A Retrospective Study from A
      Single Center in China.
AB  - BACKGROUND/AIM: This study investigated the clinicopathological factors
      associated with outcomes in patients with Luminal A breast cancer. PATIENTS AND
      METHODS: Retrospective analysis of the association of clinicopathological factors
      and breast cancer outcome in 421 patients with newly-diagnosed Luminal-A breast
      cancer that were enrolled from January 2008 to December 2014. Clinicopathological
      data were analyzed to validate the relationship with disease-free survival (DFS)
      and overall survival (OS). Kaplan-Meier curves and log-rank tests were used to
      analyze the value of clinicopathological factors (tumor size, node status and
      lymphovascular invasion), and subsequent Cox regression analysis revealed
      significant prognostic factors. RESULTS: With a median of 61 months follow-up,
      the 5-year DFS and 5-year OS rate were 98.3% and 99.3%. Cox multivariate
      regression analysis showed that clinical anatomic stage, tumor size, status of
      lymph nodes, lymphovascular invasion and systemic treatment are strong prognostic
      factors for clinical outcome in patients with Luminal-A breast cancer. Of all 413
      patients with stage I-III breast cancer, 14 presented with metastasis (3.4%)
      during the follow up. Bone (6/14, 42.9%) was the most common site of metastasis
      followed by liver (5/14, 35.7%) and lung (4/14, 28.6%). The median survival time
      after metastasis was 20.4 months. Of all the sites of distant metastasis, liver
      metastasis was the only factor that affected survival time after metastasis
      (chi2=6.263, p=0.012). CONCLUSION: Patients with Luminal A breast cancer have
      excellent outcomes. Liver metastasis is an important factor compressing the
      survival time after distant metastasis presents.

PMID- 28739752
TI  - Severe Cardiotoxicity in a Patient with Colorectal Cancer Treated with
      Bevacizumab.
AB  - BACKGROUND/AIM: Bevacizumab combined with standard chemotherapeutics has become a
      choice of treatment for several kinds of cancers. Hypertension, third-degree
      albuminuria, thrombosis and cardiotoxicity are the reported side-effects of
      bevacizumab. Among them, cardiotoxicity is a most severe, but rare outcome. We
      report a case of a 62-year-old female with colorectal carcinoma who was given
      bevacizumab-containing chemotherapy for more than 20 months and achieved a stable
      disease during the entire course of treatment. Thereafter, she developed
      cardiotoxicity including grade 3 hypertension, tricuspid regurgitation, pulmonary
      hypertension, left ventricular diastolic dysfunction and pericardial effusion,
      and was discontinued from the regimen with bevacizumab. CONCLUSION: Although
      clinically-effective, the severe cardiotoxicity of bevacizumab developed after
      over 20 courses of treatment prompted us to look for optimal chemotherapy
      prescription in order to achieve a better clinical outcome.

PMID- 28739753
TI  - Application of Ultrasound-guided Core Needle Biopsy in the Diagnosis of T3 or T4
      Stage Laryngeal and Hypopharyngeal Cancer.
AB  - AIM: To study the value of ultrasound-guided core needle biopsy (CNB) in the
      diagnosis of T3 or T4 stage laryngeal and hypopharyngeal cancer, which is
      difficult by routine methods. PATIENTS AND METHODS: Nineteen cases of T3 or T4
      stage laryngeal or hypopharyngeal carcinoma with abnormal pharyngeal sensitivity,
      severe dyspnea, submucous cancer recurrence, cardiovascular and pulmonary
      dysfunction were reviewed retrospectively from October 2012 to October 2014 in
      the Yuhuangding Hospital of Qingdao University. Ultrasound-guided coarse needle
      biopsies were used on primary lesions after assessing the patients with neck
      enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scan(s).
      The clinical value of ultrasound-guided CNB in the diagnosis of laryngeal and
      hypopharyngeal cancer was analyzed. RESULTS: All patients underwent successful
      pathological diagnosis by ultrasound-guided CNB without any serious
      complications. Dyspnea, cardiovascular and pulmonary dysfunction did not
      deteriorate. CONCLUSION: Ultrasound-guided CNB is a highly safe and efficient
      method for the pathological diagnosis of T3 or T4 stage laryngeal and
      hypopharyngeal cancer. It should be used especially when the fiberoptic or
      laryngoscope biopsy are of high risk.

PMID- 28739754
TI  - Collision of Lymphoepithelioma-like Carcinoma with Diffuse Large B-cell Lymphoma
      of the Stomach: A Case Report.
AB  - BACKGROUND/AIM: Collision of Epstein-Barr virus (EBV)-associated
      lymphoepithelioma-like carcinoma (LELC) with non-Hodgkin's lymphoma of the
      stomach is extremely rare. PATIENTS AND METHODS: Herein we report a case of LELC
      with primary diffuse large B-cell lymphoma (DLBCL) of the stomach in a 65-year
      old patient. RESULTS: Gastric endoscopy showed a poorly differentiated
      adenocarcinoma of the stomach. The patient underwent radical gastrectomy, and
      histopathological examinations revealed the collision of LELC and DLBCL of the
      stomach. In situ hybridization showed that most carcinoma cells of LELC were
      positive for EBV-encoded small RNA (EBER) suggesting that the virus infection
      happened in the early stage of tumorigenesis, while DLBCL was negative.
      CONCLUSION: This is the first report of collision of EBV-associated LELC with
      primary DLBCL of the stomach.

PMID- 28739755
TI  - Nomogram Model of LNR Predicts Survival in Premenopausal Patients with Node
      positive Luminal Breast Cancer.
AB  - AIM: The aim of this study was to assess the prognostic value of lymph node ratio
      (LNR) in premenopausal patients with luminal breast carcinoma. MATERIALS AND
      METHODS: A total of 885 female patients who presented with axillary lymph node
      positive luminal breast cancer between 2000 and 2009 were investigated. Using X
      tile, we classified patients into low-, intermediate- and high-risk groups based
      on LNR. The Kaplan-Meier method was used to determine cumulative survival curves.
      Cox proportional hazards analyses were used to identify the factors that
      contributed to disease-free (DFS) and overall (OS) survival. RESULTS: The median
      age of patients was 42 years (range=21-58 years). A training set of 295 patients
      and a validation set of 590 patients were used to determine the optimal LNR cut
      off points (0.20 and 0.63). DFS was 87.7%, 77.4% and 53.9% (p<0.001) and OS was
      91.5%, 76.7% and 50.9% (p<0.0001) for the low- (<=0.20), intermediate- (0.21
      0.63) and high-risk (>0.63) groups, respectively. The 10-year DFS and OS rates
      were significantly longer in the low-risk group than in the high-risk group.
      Nomogram analysis demonstrated that LNR contributed more compared to nodal stage
      in predicting both DFS and OS. CONCLUSION: We conclude that LNR strongly predicts
      prognosis in premenopausal patients with lymph node-positive luminal breast
      cancer.

PMID- 28739756
TI  - Better Clinical Efficiency of TILs for Malignant Pleural Effusion and Ascites
      than Cisplatin Through Intrapleural and Intraperitoneal Infusion.
AB  - BACKGROUND/AIM: To evaluate the clinical efficiency of tumor-infiltrating
      lymphocytes (TILs) compared to cisplatin for malignant pleural effusion and
      ascites through intrapleural and intraperitoneal infusion. PATIENTS AND METHODS:
      Thirteen patients with malignant pleural effusion and ascites were divided into a
      TIL-treated group and a cisplatin-treated group. Patients were given TILs or
      cisplatin, through intrapleural and intraperitoneal infusion respectively, after
      drainage of the malignant serous effusion by thoracentesis or abdominocentesis.
      RESULTS: The overall response rate and disease control rate of the TIL-treated
      group (33.33% and 83.33%) were higher than that of the cisplatin-treated group
      (28.57% and 71.43%). The progression-free survival for the TIL-treated group was
      significantly longer (p=0.002) and better than that of the cisplatin-treated
      group (66.67% vs. 28.57%). Quality of life apparently improved in the TIL-treated
      group and was clearly higher than that in the cisplatin-treated group.
      CONCLUSION: The use of TILs has a better clinical efficiency for malignant
      pleural effusion and ascites than cisplatin through intrapleural and
      intraperitoneal infusion without severe adverse effects.

PMID- 28739757
TI  - Multifocal and Multicentric Breast Carcinoma: A Significantly More Aggressive
      Tumor than Unifocal Breast Cancer.
AB  - BACKGROUND/AIM: There are still many questions that surround multifocal or
      multicentric breast carcinoma (MMBC). The aim of this study was to analyze the
      clinicopathological characteristics of MMBC and provide feasible suggestions for
      therapy. PATIENTS AND METHODS: A total of 156 cases of MMBC in 3,597 invasive
      ductal breast carcinomas were collected and reviewed. Some factors related with
      prognosis such as tumor size, lymph node metastasis and others were assessed in
      each tumor focus, and mismatches among foci were recorded. RESULTS: The majority
      of MMBC had aggregate dimensions over 2 cm (85.90%). The rate of axillary lymph
      node metastasis was 56.41% (88/156) compared to unifocal tumors of 33.01%
      (1,136/3,441). Most cases had higher Ki-67 proliferative indices (91/156).
      Mismatches in ER status were present in 6 cases, PR in 4 cases, proliferative
      index (Ki-67) in 9 cases and HER2-positive status in 2 cases. CONCLUSION: The
      larger aggregate dimension of tumor, the higher metastatic rate of axillary lymph
      node and the high Ki-67 proliferative index seen in most cases, suggest that MMBC
      is biologically more aggressive than unifocal breast cancer. In addition, every
      focus should be tested owing to the existence of different expressions of
      immunostaining between foci.

PMID- 28739758
TI  - Laparoscopic-assisted Transanal Total Mesorectal Excision for Middle-Low Rectal
      Carcinoma: A Clinical Study of 19 Cases.
AB  - AIM: To explore the safety, feasibility and short-term outcomes of laparoscopic
      assisted transanal total mesorectal excision (La-TaTME) of middle-low rectal
      carcinoma. MATERIALS AND METHODS: This retrospective research collected and
      analyzed the clinical data of 19 patients diagnosed with middle and low rectal
      carcinoma who underwent La-TaTME from August 2015 to February 2017. RESULTS: No
      case was converted to laparotomy. In none of the enrolled cases, did the
      circumferential resection margin test positive by histopathology examination.
      Also, there was no detected residual tumor at the proximal and distal resection
      margins. The rate of postoperative morbidity was 15.8% (Clavien-Dindo grade 2).
      During the follow-up period, no local recurrence or metastasis was observed.
      CONCLUSION: La-TaTME is a safe alternative to standard laparoscopic TME in middle
      low rectal carcinoma when operated by an experienced colorectal surgeon. However,
      large-scaled randomized multi-centered comparative trials are still needed to
      further test its oncological effectiveness.

PMID- 28739759
TI  - Explored Risk Factors for Lymph Node Metastasis with Siewert II/III
      Adenocarcinoma of the Gastroesophageal Junction.
AB  - AIM: To explore the risk factors and prognosis for lymphatic metastasis (LNM) in
      patients with Siewert II/III adenocarcinoma of the gastroesophageal junction
      (AEG). PATIENTS AND METHODS: This study retrospectively reviewed 49 patients with
      Siewert II/III AEG. Clinical characteristics and pathological features were
      analyzed by the Chi-square the and binary logistic regression. Survival data were
      analyzed using the Kaplan-Meier method. RESULTS: LNM frequency was found in lymph
      nodes No.1, No.2, No.3, No.7, No.11 and No.110. The results revealed that depth
      of infiltration, neoplasms by histological type and lymphatic embolus were
      independent risk factors for LNM. The 1- and 3-year survival of patients without
      LNM were both 100%, while patients with LNM had 70% and 60% survival,
      respectively. Although the differences were not statistically significant,
      survival rate with negative lymph nodes was higher than in patients with LNM.
      CONCLUSION: Total gastrectomy combined with D2 No.110 lymphadenectomy might
      improve the prognosis for LNM patients.

PMID- 28739760
TI  - Cyclosporin A Reversed Chemoresistance of a Patient with Pure Red Cell Aplasia
      Secondary to Thymoma.
AB  - CASE REPORT: This case study reports on a patient who relapsed with thymoma
      (mixed type) nine years after tumor resection. After four courses of rescue
      chemotherapy (docetaxel and cisplatinum), the patient was further diagnosed with
      pure red cell aplasia. It was noticed that cyclosporin A (CsA), which was
      administered to treat aplasia, could reverse chemoresistance. Its mechanism is
      not completely clear, but the hypothesis of CsA inhibiting P-glycoprotein
      mediated drug efflux is the most acceptable.

PMID- 28739761
TI  - The Prognostic Value of the 8th Edition of the American Joint Committee on Cancer
      (AJCC) Staging System in HER2-Enriched Subtype Breast Cancer, a Retrospective
      Analysis.
AB  - BACKGROUND/AIM: The American Joint Committee on Cancer (AJCC) released its 8th
      edition of tumor staging which is to be implemented in early 2018. The present
      study aimed to analyze the prognostic value of AJCC 8th edition Cancer Staging
      System in HER2-enriched breast cancer, on a retrospective cohort. PATIENTS AND
      METHODS: This study was a retrospective single-center study of HER2-enriched
      breast cancer cases diagnosed from January 2008 to December 2014.
      Clinicopathological features and follow up data including disease-free survival
      (DFS) and overall survival (OS) were analyzed to explore prognostic factors for
      disease outcome. We restaged patients based on the 8th edition of the AJCC cancer
      staging system and analyzed prognostic value of the Anatomic Stage Group and the
      Prognostic Stage Group. RESULTS: The study enrolled 170 HER2-enriched subtype
      breast cancer patients with 5-year disease free survival (DFS) of 85.1% and 5
      year overall survival (OS) of 86.8%. Prognostic stages of 117 cases (68.8%)
      changed compared with anatomic stages, with 116 upstaged cases and 1 downstaged
      case. The Anatomic Stage Groups had a significant prognostic impact on DFS
      (chi2=16.752, p<0.001) and OS (chi2=25.038, p<0.001). The Prognostic Staging
      Groups had a significant prognostic impact on DFS (chi2=6.577, p=0.037) and OS
      (chi2=21.762, p<0.001). In the multivariate analysis, both stage groups were
      independent predictors of OS. CONCLUSION: Both Anatomic and Prognostic Stage
      Groups in the 8th edition of the AJCC breast cancer staging system had prognostic
      value in HER2-enriched subtype breast cancer. The Prognostic Stage system was a
      breakthrough on the basis of anatomic staging system.

PMID- 28739762
TI  - Comparison of Efficiency of Video Endoscopy and Open Inguinal Lymph Node
      Dissection.
AB  - AIMS: To compare the efficiency and complications of video endoscopy, inguinal
      lymphadenectomy and open inguinal lymph node dissection. PATIENTS AND METHODS:
      Nineteen video endoscopy inguinal lymphadenectomies were performed on 16 patients
      from September 2014 to December 2015, and 21 open inguinal lymph node dissections
      were performed on 18 patients from September 2013 to September 2014. Surgical
      time, operative blood loss, incidence of complications, length of stay, lymph
      node harvest and suture removal time were compared between the two groups.
      RESULTS: Operative time (135.5+/-45.52 vs. 169.8+/-55.19 min), lymph node harvest
      (10.78+/-5.22 vs. 12.60+/-5.53), and hospital stay (10.43+/-2.53 vs. 12.50+/-4.98
      days) did not statistically differ between the two groups (p>0.05). However,
      operative blood loss (22.50+/-14.24 vs. 68.44+/-42.19 ml), drainage tube removal
      time (7.23+/-1.79 vs. 11.44+/-2.69 days), incidence of complications (21.05% vs.
      61.9%), and suture removal time (7.52+/-1.24 vs. 12.81+/-2.04 min) were
      significantly reduced in the video endoscopy surgery group compared with the open
      surgery group (p<0.05). CONCLUSION: Compared with open surgery, video endoscopy
      surgery achieved the same efficiency, and had the advantage of reduction of
      complications, suture removal time and in-surgery blood loss.

PMID- 28739763
TI  - Exploration of the Radiotherapeutic Clinical Target Volume Delineation for
      Gastric Cancer from Lymph Node Metastases.
AB  - AIM: To clarify the clinical target volume of regional lymph nodes (CTVn)
      delineation of gastric adenocarcinoma. MATERIALS AND METHODS: The pattern of
      lymph node metastases (LNM) of a total of 1,473 patients with gastric cancer (GC)
      who had undergone gastrectomy and lymphadenectomy with more than 15 lymph nodes
      retrieved was retrospectively examined. RESULTS: A univariate analysis showed
      that T stage (p<0.001), macroscopic type (p=0.001), tumor differentiation
      (p<0.001), maximum diameter of tumor (p<0.001) as well as cancer embolus
      (p<0.001) were closely associated with the rate of LNM. While by multivariate
      analysis, gender [odds ratio (OR=0.687, p<0.05], maximum diameter (OR=1.734,
      p<0.001), tumor differentiation (OR=1.584, p<0.001), T stage (OR=2.066, p<0.001)
      and cancer embolus (OR=4.912, p<0.001) were strongly associated with the rate of
      LNM. CONCLUSION: In conclusion, for male patients with GC with large, deeply
      invasive, poorly differentiated, diffusely infiltration and positive cancer
      embolus, the radiation fields should be enlarged appropriately.

PMID- 28739764
TI  - MR-guided Percutaneous Biopsy of Focal Hepatic Dome Lesions with Free-hand
      Combined with MR Fluoroscopy Using 1.0-T Open High-field Scanner.
AB  - AIM: To prospectively estimate the safety, feasibility and accuracy of 1.0T open
      magnetic resonance (MR)-guided percutaneous biopsy in free-hand of focal lesions
      located in the hepatic dome. MATERIALS AND METHODS: All percutaneous MR-guided
      biopsies of the lesions were performed at the Shandong Medical Imaging Research
      Institute. Thirty-six patients with focal liver lesions located in the hepatic
      dome measuring 6-36 mm in the maximum diameter were included in this study.
      Lesions were divided into two groups on the basis of maximum nodule diameters:
      <=1.5 cm (n=14) and >1.5 cm (n=22). Surgical pathology of nodules or clinical and
      imaging follow-up for at least 12 months were used to establish final diagnosis.
      Diagnostic accuracy, specificity, sensitivity, average procedure time and
      complications were recorded and analyzed. RESULTS: All obtained samples were
      sufficient for diagnosis. Accuracy, sensitivity and specificity of MRI-guided
      percutaneous liver lesions biopsy in diagnosing malignant tumors were 97.2%,
      96.7% and 100%, respectively. Accuracy, sensitivity and specificity were 92.9%,
      90.9% and 100% for the lesions that were 1.5 cm or smaller in diameter and 100%,
      100% and 100% for lesions larger than 1.5 cm in diameter, respectively. There was
      no significant difference between the two groups (p>0.05). The average procedure
      time for each pass of the needle from skin entry to the target lesion was 1.1 min
      and the total procedural time was 28.5 min. Biopsy-induced complications included
      peri-hepatic hemorrhage in 8.3% (3/36) of cases. No serious complications
      occurred. CONCLUSION: 1.0T open-MR-guided free-hand percutaneous biopsy is a
      safe, feasible and highly accurate diagnostic method for pathological diagnosis
      of focal liver lesions located in the hepatic dome.

PMID- 28739765
TI  - Relationship of Th17/Treg Cells and Radiation Pneumonia in Locally Advanced
      Esophageal Carcinoma.
AB  - BACKGROUND/AIM: Radiation pneumonia is a main side-effect that has limited the
      clinical usage of radiotherapy in locally advanced esophageal carcinoma. T helper
      cells 17 (Th 17) and T regulatory cells (Tregs) play an important role in
      inflammatory diseases. The balance between Treg and Th17 cells is a key factor in
      the progression of many inflammatory and autoimmune diseases. Whether Tregs and
      Th17 cells are predictive factors of radiation pneumonia has not yet been
      reported. In this study, we investigated the relationships of Treg/Th17 cells and
      radiation pneumonia in patients with locally advanced esophageal cancer who
      received radiotherapy. PATIENTS AND METHODS: One hundred and forty-eight patients
      with locally advanced esophageal cancer who received radical and palliative
      radiotherapy were enrolled. The levels of Th17 and Treg cells in the blood of
      patients were detected using flow cytometry at the time point of pre
      radiotherapy, 1st, 2nd, 3rd, 4th, 5th and 6th week from the start of radiation
      and 4 weeks after completion of radiotherapy. Radiation pneumonia was evaluated
      according to Radiation Therapy Oncology Group's acute radiation pneumonia
      standards, with the endpoint being grade 2 or above radiation pneumonia. RESULTS:
      There were 24 cases of radiation pneumonia in 148 cases of locally advanced
      esophageal cancer patients who underwent radiotherapy. Th17 cells increased and,
      in contrast, Treg cells decreased in the radiation pneumonia group. The change in
      the ratio of Th17/Treg was more pronounced and the difference was statistically
      significant from the 5th week after irradiation compared to patients with no
      radiation pneumonia (p<0.05). There was no significant difference in dosimetric
      parameters, including V5, V20, V30 and mean lung dose (MLD) and clinical factors,
      such as gender, age, smoking history, history of surgery and chemotherapy.
      CONCLUSION: The ratio of Th17/Treg cells may be an effective predictive factor of
      radiation pneumonia.

PMID- 28739766
TI  - Clinical Study on Using 125I Seeds Articles Combined with Biliary Stent
      Implantation in the Treatment of Malignant Obstructive Jaundice.
AB  - Aim: To study the feasibility and curative effect of 125 I seeds articles
      combined with biliary stent implantation in the treatment of malignant
      obstructive jaundice. Patients and Methods: Fifty patients with malignant
      obstructive jaundice were included. Twenty-four were treated by biliary stent
      implantation combined with intraluminal brachytherapy by 125I seeds articles as
      the experimental group, while the remaining 26 were treated by biliary stent
      implantation only as the control group. The goal of this study was to evaluate
      total bilirubin, direct bilirubin and tumor markers (cancer antigen (CA)-199, CA
      242 and carcinoembryonic antigen (CEA)), as well as biliary stent patency status
      and survival time before and after surgery. Results: Jaundice improved greatly in
      both groups. The decreases of CA-199 and CA-242 had statistical significance
      (p=0.003 and p=0.004) in the experimental group. The ratio of biliary stent
      patency was 83.3% (20/24) in the experimental group and 57.7% (15/26) in the
      control group (p=0.048). The biliary stent patency time in the experimental group
      was 1~15.5 (mean=9.84) months. The biliary stent patency time in the control
      group was 0.8~9 (mean=5.57) months, which was statistically significant
      (p=0.018). The median survival time was 10.2 months in the experimental group,
      while 5.4 months in control group (p<0.05). Conclusion: 125 I seeds articles
      combined with biliary stent implantation significantly prolongs biliary stent
      patency time and survival time for patients with malignant obstructive jaundice
      possibly by inhibiting the proliferation of vascular endothelial cells and the
      growth of tumor. 

PMID- 28739767
TI  - Predictors of Malignancy for Female Patients with Suspicious Nipple Discharge: A
      Retrospective Study.
AB  - BACKGROUND: Suspicious nipple discharge (ND) in females requires further
      treatment, including biopsy or selective duct excision. It is important to
      identify predictors of malignancy in female patients with suspicious ND.
      MATERIALS AND METHODS: This retrospective study included patients with suspicious
      ND who underwent surgical treatment at our center between January 2007 and
      December 2014. Clinicopathological features were compared between patients with
      and without malignancy. We used a Chi-square test and a logistic regression model
      as the univariate and multivariate analysis for identification of predictors of
      malignancy. RESULTS: A total of 334 patients were eligible and included. The
      median age of the study population was 45 (range=19-81) years; 18.0% (60/334) of
      the entire study population had breast cancer. The univariate analysis suggested
      that older age (p=0.002) and presence of suspicious lumps (p<0.001) were
      significantly associated with malignancy. In contrast, presence of bloody
      discharge was not significantly associated with malignancy (p=0.324). The
      multivariate analysis confirmed that older age (p=0.023) and presence of
      suspicious lumps (p<0.001) were independent predictors of malignancy. For
      patients without suspicious lumps, we did not observe any association between the
      presence of bloody discharge and malignancy. For patients with suspicious lumps,
      tumor size was significantly associated with malignancy (p<0.001). CONCLUSION:
      Our study suggests that older age and the presence of suspicious lumps are
      predictors of the presence of malignancy in females with suspicious ND.

PMID- 28739768
TI  - Preoperative High Neutrophil-to-Lymphocyte Ratio Is Associated with High-grade
      Bladder Cancer.
AB  - AIM: To evaluate the correlation between the neutrophil-to-lymphocyte ratio (NLR)
      and histopathological characteristics of bladder cancer. MATERIALS AND METHODS: A
      retrospective analysis was performed on a cohort of patients (n=302) who were
      diagnosed with bladder cancer and underwent transurethral resection of bladder
      tumor or cystectomy between 2009 and 2016. The pathological outcomes were
      compared between patients with low NLR and those with high NLR with a cut-off
      value of 2.5, and a logistic regression analysis was performed to find potential
      predictors of pathological tumor outcomes. RESULTS: Patients with high-grade
      disease had significantly higher NLRs compared to those with low-grade disease
      (median NLR=4.42 vs. 3.42, p<0.001). Univariate analysis suggested that age,
      neutrophil count and NLR, as a continuous or binary variable, were significantly
      associated with high-grade disease. Multivariate analysis suggested that age and
      NLR, as a continuous variable, were predictors of pathologically high-grade
      disease. CONCLUSION: Preoperative NLR was found to be associated with
      pathological tumor grading, but was not associated with pathological tumor
      staging in patients with bladder cancer.

PMID- 28739769
TI  - Effects of Different Palliative Jaundice Reducing Methods on Immunologic
      Functions in Patients with Advanced Malignant Obstructive Jaundice.
AB  - BACKGROUND/AIM: This study aimed to investigate the effects of three treatment
      methods on the immunological function of patients with advanced malignant
      obstructive jaundice (MOJ). PATIENTS AND METHODS: Patients with advanced MOJ were
      randomly divided into three groups according to biliary drainage methods.
      Detection of levels of multi-indices were investigated in different time periods.
      RESULTS: After drainage, the levels of complement 3 (C3) and complement 4 (C4)
      were increased. Forteen days post-operation, the levels of immunoglobulin G
      (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) in the group undergoing
      palliative surgery decreased significantly compared to those in both percutaneous
      transhepatic cholangio drainage (PTCD) and endoscopic retrograde biliary drainage
      (ERBD) groups. The level of serum endotoxin in the group undergoing palliative
      surgery decreased gradually. CONCLUSION: Palliative surgery for reducing jaundice
      is superior to PTCD and ERBD in improving immune function of patients with MOJ.

PMID- 28739770
TI  - Gastric Cancer Mortality Trends in China (2006-2013) Reveal Increasing Mortality
      in Young Subjects.
AB  - BACKGROUND/AIM: Although the advent of Helicobacter pylori eradication and global
      societal changes are widely assumed to impact on gastric cancer (GC)-related
      mortality, there is remarkable little quantitative and qualitative insight into
      the nature of its effects. Here, we exploited a nationwide reporting system to
      investigate the epidemiological features of GC-related mortality in China between
      2006 and 2013. PATIENTS AND METHODS: GC mortality data between 2006 and 2013 were
      obtained from the National Disease Surveillance System published by the China
      Center for Disease Control and Prevention (CDC). RESULTS: GC mortality increased
      by 8.2% (from 18.87/100,000 to 20.41/100,000), while GC mortality standardized by
      the age scale of the population in 2010 decreased by 17.8% (from 21.87/100,000 to
      17.98/100,000). Standardized GC mortality in males (25.66/100,000 to
      33.89/100,000) was higher compared to females (10.72/100,000 to 14.79/100,000),
      while standardized GC mortality in rural areas (19.17/100,000 to 26.46/100,000)
      was higher than in urban areas (15.48/100,000 to 20.04/100,000). Both crude and
      standardized rates in the 0- to 29-year-old group increased by 22.3% and 16.2%,
      respectively; while these rates declined in the 30- to 59-year-old group and over
      60-year-old group. The proportion of GC deaths that accounts for all cancer
      deaths declined from 15.99% (2006) to 13.6% (2013); however, the proportion in
      the 0- to 29-year-old group revealed an increasing trend from 2006 (3.20%) to
      2013 (3.87%). CONCLUSION: Our results reveal a remarkable increase in GC-related
      mortality in subjects under the age of 30 calling for further measures to prevent
      the increase in the incidence of GC in young patients.

PMID- 28739771
TI  - Clinical Characteristics and Prognosis of Elderly Small Cell Lung Cancer Patients
      Complicated with Hyponatremia: A Retrospective Analysis.
AB  - AIM: This study was designed to evaluate the clinical characteristics and
      prognosis of elderly small cell lung cancer (SCLC) patients complicated with
      hyponatremia, thus providing increased attention for appropriate intervention and
      improving outcomes in symptomatic subjects. PATIENTS AND METHODS: The clinical
      data of 320 patients with SCLC in the Yuhuangding Hospital from March 1st, 2006,
      to March 1st, 2012, were studied retrospectively. The prognosis and possible
      association with hyponatremia was investigated. RESULTS: The incidence rate of
      hyponatremia in SCLC was 46.56% (149/320). The mean survival time was 1.10+/-0.42
      years in patients with normal values and 0.83+/-0.35 years in patients with
      subnormal serum sodium. In the hyponatremia group, the mean survival time of
      corrected hyponatremia patients was 0.91+/-0.42 years, which was significantly
      longer than uncorrected hyponatremia patients whose mean survival time was 0.68+/
      0.26 years (t=2.75, p<0.05) after symptomatic treatment. The mean survival time
      of the normal group and the hyponatremia group in elderly patients had a tendency
      to decrease when compared to another group of patients younger than 60 years old.
      Hyponatremia at 1- and 3-year follow-up was associated with worse survival rates
      (p<0.05). CONCLUSION: The severity of hyponatremia has unfavorable prognostic
      impacts. Elderly SCLC patients with hyponatremia are difficult to cure and
      associated with significantly shorter survival, especially in the uncorrected
      group. It is important that the cause of the hyponatremia is diagnosed at an
      early stage and precise medical treatment is provided.

PMID- 28739772
TI  - Efficacy and Safety of Nab-Paclitaxel as Second-line Chemotherapy for Locally
      Advanced and Metastatic Non-small Cell Lung Cancer.
AB  - AIM: To investigate the efficacy and safety of nanoparticle albumin-bound
      paclitaxel (nab-paclitaxel) for locally advanced or metastatic non-small cell
      lung cancer (NSCLC) as second-line chemotherapy. PATIENTS AND METHODS: We
      retrospectively reviewed the treatment of 34 patients with advanced NSCLC whose
      first-line treatment had failed. These patients received nab-paclitaxel 260 mg/m2
      on day 1 and day 8 of a 21-day cycle from July 2014 to February 2016. One cycle
      of treatment lasted 3 weeks and all patients completed more than two cycles. All
      patients were assessed for adverse events related to treatment. RESULTS: No
      patient achieved complete response (CR); 12 patients reached partial response
      (PR), 12 patients achieved stable disease (SD) and 10 patients progressive
      disease (PD). The overall response rate (ORR) was 35.3% and the disease control
      rate (DCR) 70.6 %. There was no significant difference in either ORR or DCR
      within the subgroups. The median progression-free survival (PFS) was 5.7 months
      (95% confidence interval (CI)=3.8-7.6) and the median overall survival (OS) was 9
      months (95% CI=8.3-9.7). There was no statistical difference in OS (p=0.066), but
      subgroup analysis showed that patients with squamous carcinoma benefited more in
      PFS (the median PFS of squamous carcinoma vs. adenocarcinoma was 7.3 months vs. 5
      months, p=0.001). Major adverse events included myelosuppression,
      gastrointestinal response, baldness, myalgia and neurotoxicity. Hypersensitivity
      reactions were not reported. CONCLUSION: Nab-paclitaxel is an effective
      chemotherapy for locally advanced and metastatic NSCLC as treatment and has a
      superior application prospect for squamous NSCLC. Toxicity is generally mild and
      manageable.

PMID- 28739773
TI  - Independent Correlation Between Ki67 Index and Circulating Tumor Cells in the
      Diagnosis of Colorectal Cancer.
AB  - BACKGROUND: The Ki67 index is a biomarker of proliferation, while the circulating
      tumor cell (CTC) count acts as a metastasis-related biomarker. In this study, we
      analyzed the potential value of CTC count and Ki67 index in diagnosis of
      colorectal cancer (CRC). MATERIALS AND METHODS: A total of 105 patients with CRC
      undergoing surgery were included in the study. Isolation and identification of
      CTCs were performed by negative enrichment and immuno-fluorescence in situ
      hybridization, respectively. Expression of Ki67 was assessed by
      immunohistochemistry. RESULTS: Patients with CTC count >=2 were defined as CTC
      positive. Ki67 index >=50% was regarded as highly proliferative. Overall, 71
      cases were CTC-positive, while 82 cases displayed a high Ki67 index. CTC count
      and Ki67 index had no correlation with tumor size, tumor site, age, gender and
      TNM stages of the patients. CTC count was correlated with tumor size (p=0.018)
      and Ki67 index with level of differentiation (p<0.001). However, there was no
      relationship between CTC count and Ki67 index (p=0.198). CONCLUSION: Our results
      suggest that CTCs can act as a potent metastasis-related biomarker for the
      diagnosis of CRC, independently of the Ki67 index.

PMID- 28739774
TI  - Study of Preoperative Antiviral Treatment of Patients with HCC Negative for HBV
      DNA.
AB  - AIM: To study preoperative HBV-DNA negative HBV-related hepatocellular carcinoma
      (HCC) which was reactivated after surgery and could influence liver function and
      HCC recurrence. PATIENTS AND METHODS: Patients were divided into two groups
      according to preoperative antiviral therapy status. The control group comprised
      of 102 preoperative HBV-DNA-negative patients who had not undergone antiviral
      therapy before surgery. In the treatment group, all HBV-DNA-negative patients
      (n=63) received entecavir 3-5 days before surgery and for 12 months after
      surgery. Patients were followed-up regularly, during the preoperative period, and
      at 1, 3, 6, 12, 18, 24, 30 and 36 months postoperatively. The data for the two
      groups were analyzed including the level of HBV-DNA and HBV-DNA activation; liver
      function; 1-, 2- and 3-year survival rate; cumulative survival time; and tumor
      recurrence. RESULTS: Liver function in the treatment group was better than that
      of the control group12 months after surgery. Compared to the control group, total
      bilirubin in the treatment group was significantly better at 6 and 12 months
      after surgery (p<0.05 and p<0.001, respectively). Serum albumin, alanine
      aminotransferase and prothrombin time in the treatment group was significantly
      better than that of controls 12 months after surgery (p<0.001). In the treatment
      group, two cases (3.17%) had HBV-DNA activation while there were 13 cases
      (12.75%) with HBV-DNA activation in the control group (p<0.05). There were 51
      cases with tumor recurrence in the control group, that was statistically
      significantly higher than recurrent cases in the treatment group (p<0.05).
      Postoperative 1-, 2- and 3-year cumulative overall survival rates were 94.12%,
      81.37% and 52.94%, respectively, for the control group and 93.65%, 77.78% and
      71.43%, respectively, for the treatment group (p=0.006). There was no
      statistically significant difference in disease-free survival between the two
      groups (p=0.231). CONCLUSION: Antiviral treatment of HBV-related HCC with
      negative HBV-DNA is beneficial to liver function, coagulation function, disease
      control, prevention of tumor recurrence, improvement of patient quality of life,
      reduces the death rate and prolongs survival duration.

PMID- 28739775
TI  - Effect of Interventional Therapy on the Expression of Survivin mRNA in Cervical
      Cancer.
AB  - AIM: To examine the expression of survivin mRNA in cervical squamous cancer at
      different time points during interventional therapy in order to find the optimal
      time point for continual treatment. PATIENTS AND METHODS: Fifty patients with
      stage IB2-IIB cervical squamous cancer receiving transarterial infusion
      chemotherapy and chemoembolization were included in the present study. The
      expression of survivin mRNA in cancer samples before and after interventional
      therapy (on days 7, 14 and 21) were examined by reverse transcription-polymerase
      chain reaction. RESULTS: The expression of survivin mRNA in cancer samples before
      the interventional therapy was significantly higher than that of any time point
      after the interventional therapy (p<0.05). After treatment, the expression of
      survivin mRNA decreased until day 14. CONCLUSION: The expression of survivin mRNA
      was inhibited by the interventional therapy. It seems that day 14 after
      interventional treatment is the right time point for continuation of treatment.

PMID- 28739776
TI  - Phase II Study of the Efficacy and Safety of High-dose Pemetrexed in Combination
      with Cisplatin Versus Temozolomide for the Treatment of Non-small Cell Lung
      Cancer with Brain Metastases.
AB  - The aim of this study was to explore the efficacy and safety of high-dose
      pemetrexed with cisplatin versus combination with temozolomide in patients with
      brain metastases (BM) of lung adenocarcinoma. After standard whole-brain
      radiotherapy (WBRT, 30 Gy/10 fractions), patients with BM of non-small cell lung
      cancer (NSCLC) were given high-dose pemetrexed (900 mg/m2) on day 1 of each cycle
      (3 weeks), and cisplatin was administered on days 1-3 in the cisplatin-treated
      group. The temozolomide-treated group was treated as follows: 75 mg/m2
      temozolomide orally with concurrent WBRT followed by 150 mg/m2 temozolomide on
      days 1-5 with high-dose pemetrexed (900 mg/m2) on day 1 of each cycle (3 weeks).
      Six cycles later, high-dose pemetrexed (900 mg/m2) monotherapy or the best
      available supportive therapy was administered to both groups. An evaluation was
      carried out every 2-3 cycles. The primary end-points were objective response rate
      (ORR), progression-free survival (PFS), and overall survival (OS). Secondary end
      points included safety and tolerability. Thirty-two patients in the pemetrexed
      plus cisplatin (PC) group and 28 patients in the pemetrexed plus temozolomide
      (PT) group were enrolled from November 2013 to October 2015. The ORR was 68.8%
      and 75%, in the PC and PT groups, respectively, and there was no statistically
      significant difference between the two groups (p=0.711). The median PFS rates of
      the PC and PT groups were 13.6 months and 16.9 months, respectively, and the
      median OS rates of the PC and PT groups were 18.9 months and 19.3 months,
      respectively. There were no differences in PFS and OS between the two groups.
      There were no grade 4 or higher side-effects in either group, but grade 3 side
      effects such as leucopenia (2/32, 6.3%), nausea/vomiting (2/32, 6.3%), alopecia
      (1/32, 3.1%), rash (3/32, 9.4%) and renal insufficiency (1/32, 3.1%) were
      observed in the PC group, whereas the PT-group-only showed the following grade 3
      side-effects: leucopenia (1/28, 3.6%) and nausea/vomiting (2/28, 7.1%). The data
      showed that the PT group achieved the same efficacy in PFS and OS as the PC group
      but with fewer toxicities. Therefore, high-dose pemetrexed plus temozolomide may
      be a better regimen for treating NSCLC with BM due to its better safety.

PMID- 28739777
TI  - Establishment of a comprehensive drug overdose fatality surveillance system in
      Kentucky to inform drug overdose prevention policies, interventions and best
      practices.
AB  - BACKGROUND: According to the National Center for Health Statistics, Kentucky had
      the third highest drug overdose fatality rate in the nation in 2015 at 29.9 drug
      overdose fatalities per 100 000 population. OBJECTIVE: The elevated drug overdose
      fatality rate necessitated the development and implementation of a comprehensive
      multisource drug overdose fatality surveillance system (DOFSS). METHODS: DOFSS
      stakeholder work group members and data sources were identified, and memorandums
      of understanding were established. The following data sources were used to
      establish DOFSS: (1) death certificates; (2) autopsy reports; (3) toxicology
      result reports; (4) coroner reports; and (5) Kentucky All Schedule Prescription
      Electronic Reporting (KASPER) (prescription drug monitoring programme) data. Drug
      overdose poisonings were defined using Injury Surveillance Workgroup 7
      definitions. Analyses were performed to investigate possible drug overdose
      related health disparities for disabled drug overdose decedents and to
      characterise gabapentin in drug overdose deaths. RESULTS: DOFSS identified 2106
      drug overdose poisoning fatalities in Kentucky for 2013-2014. Identification of
      specific drugs involved in drug overdose deaths increased from 75.8% using a
      single data source to 97.5% using multiple data sources. Disabled drug overdose
      decedents were significantly more likely to have an active prescription for drugs
      identified in their system compared with the non-disabled drug overdose
      decedents. Toxicology data showed increased gabapentin involvement in drug
      overdose deaths from 2.9% in 2013 to 17% in 2014. Alprazolam was found most often
      in combination with gabapentin (41%), along with various other benzodiazepines
      and prescription opioids. CONCLUSIONS: A comprehensive multisource DOFSS improved
      drug overdose fatality surveillance by increasing completeness of data and data
      quality. DOFSS is a model that can be considered by other states to enhance their
      efforts in tracking drug overdose fatalities, identifying new and emerging
      trends, and informing policies and best practices, to address and reduce drug
      overdoses.

PMID- 28739778
TI  - A multilevel analysis of risk and protective factors for Canadian youth injured
      or killed by interpersonal violence.
AB  - PURPOSE: The study's purpose was to determine individual-level and neighbourhood
      level risk and protective factors for severe intentional injury among youth.
      METHODS: We conducted a multilevel case-control study using registry data to
      determine individual-level and neighbourhood-level social determinants associated
      with severe violent injury/homicide among youth from Winnipeg, Manitoba. RESULTS:
      The study includes 13 206 youth, aged 12-24 years (1222 cases, 11 984 controls).
      Individual-level risk predictors of being a victim of violence were male sex (OR
      5.72 (95% CI 4.77 to 6.86)) and First Nations (OR 2.76 (95% CI 2.32 to 3.29)).
      Education was inversely associated with victimisation for individuals under (OR
      0.36 (95% CI 0.26 to 0.51)) and over (OR 0.58 (95% CI 0.49 to 0.69)) 18 years.
      Ever having been in protective care (OR 1.66 (95% CI 1.39 to 1.99)), receiving
      income assistance from the government (OR 1.26 (95% CI 1.05 to 1.51)) or ever
      having criminal charges (OR 4.76 (95% CI 4.08 to 5.56)) were also significant
      predictors of being a victim of violence. Neighbourhood-level risk factors for
      victimisation included low socioeconomic status (OR 1.14 (95% CI 1.04 to 1.25))
      and high levels of assault (OR 1.07 (95% CI 1.04 to 1.10)). CONCLUSIONS: This
      study demonstrates a complex web of risk and protective factors among youth
      injured by violence. It underscores the ongoing, injurious effects of historical
      trauma experienced by many Canadian First Nations people. Strong victim
      perpetrator overlap suggests that intersectoral policies are needed to address
      these issues. Our findings highlight the need to improve education and family
      supports.

PMID- 28739779
TI  - In Vitro Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine,
      Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in
      Beijing, China.
AB  - Extensively drug-resistant tuberculosis (XDR-TB) is a deadly form of TB that can
      be incurable due to its extreme drug resistance. In this study, we aimed to
      explore the in vitro susceptibility to bedaquiline (BDQ), delamanid (DMD),
      linezolid (LZD), clofazimine (CLO), moxifloxacin (MFX), and gatifloxacin (GAT) of
      90 XDR-TB strains isolated from patients in China. We also describe the genetic
      characteristics of XDR-TB isolates with acquired drug resistance. Resistance to
      MFX, GAT, LZD, CLO, DMD, and BDQ was found in 82 (91.1%), 76 (84.4%), 5 (5.6%), 5
      (5.6%), 4 (4.4%), and 3 (3.3%) isolates among the XDR-TB strains, respectively.
      The most frequent mutations conferring fluoroquinolone resistance occurred in
      codon 94 of the gyrA gene (57.8%), and the strains with these mutations (69.2%)
      were associated with high-level MFX resistance compared to strains with mutations
      in codon 90 (25.0%) (P < 0.01). All 5 CLO-resistant isolates exhibited >=4-fold
      upward shifts in the BDQ MIC, which were attributed to mutations of codons 53
      (60.0%) and 157 (20.0%) in the Rv0678 gene. Additionally, mutation in codon 318
      of the fbiC gene was identified as the sole mutation related to DMD resistance.
      In conclusion, our data demonstrate that the XDR-TB strains exhibit a strikingly
      high proportion of resistance to the current anti-TB drugs, whereas BDQ, DMD,
      LZD, and CLO exhibit excellent in vitro activity against XDR-TB in the National
      Clinical Center on TB of China. The extensive cross-resistance between OFX and
      later-generation fluoroquinolones indicates that MFX and GAT may have difficulty
      in producing the desired effect for XDR-TB patients.

PMID- 28739780
TI  - Multicenter Evaluation of Ceftazidime-Avibactam and Ceftolozane-Tazobactam
      Inhibitory Activity against Meropenem-Nonsusceptible Pseudomonas aeruginosa from
      Blood, Respiratory Tract, and Wounds.
AB  - The recent escalation of occurrences of carbapenem-resistant Pseudomonas
      aeruginosa has been recognized globally and threatens to erode the widespread
      clinical utility of the carbapenem class of compounds for this prevalent health
      care-associated pathogen. Here, we compared the in vitro inhibitory activity of
      ceftazidime-avibactam and ceftolozane-tazobactam against 290 meropenem
      nonsusceptible Pseudomonas aeruginosa nonduplicate clinical isolates from 34 U.S.
      hospitals using reference broth microdilution methods. Ceftazidime-avibactam and
      ceftolozane-tazobactam were active, with ceftolozane-tazobactam having
      significantly higher inhibitory activity than ceftazidime-avibactam. The
      heightened inhibitory activity of ceftolozane-tazobactam was sustained when the
      site of origin (respiratory, blood, or wound) and nonsusceptibility to other beta
      lactam antimicrobials was considered. An extensive genotypic search for
      enzymatically driven beta-lactam resistance mechanisms revealed the exclusive
      presence of the VIM metallo-beta-lactamase among only 4% of the subset of
      isolates nonsusceptible to ceftazidime-avibactam, ceftolozane-tazobactam, or
      both. These findings suggest an important role for both ceftazidime-avibactam and
      ceftolozane-tazobactam against carbapenem-nonsusceptible Pseudomonas aeruginosa
      Further in vitro and in vivo studies are needed to better define the clinical
      utility of these novel therapies against the increasingly prevalent threat of
      multidrug-resistant Pseudomonas aeruginosa.

PMID- 28739781
TI  - Structural Insights into the TLA-3 Extended-Spectrum beta-Lactamase and Its
      Inhibition by Avibactam and OP0595.
AB  - The development of effective inhibitors that block extended-spectrum beta
      lactamases (ESBLs) and restore the action of beta-lactams represents an effective
      strategy against ESBL-producing Enterobacteriaceae We evaluated the inhibitory
      effects of the diazabicyclooctanes avibactam and OP0595 against TLA-3, an ESBL
      that we identified previously. Avibactam and OP0595 inhibited TLA-3 with apparent
      inhibitor constants (Kiapp) of 1.71 +/- 0.10 and 1.49 +/- 0.05 MUM, respectively,
      and could restore susceptibility to cephalosporins in the TLA-3-producing
      Escherichia coli strain. The value of the second-order acylation rate constant
      (k2/K, where k2 is the acylation rate constant and K is the equilibrium constant)
      of avibactam [(3.25 +/- 0.03) * 103 M-1 . s-1] was closer to that of class C and
      D beta-lactamases (k2/K, <104 M-1 . s-1) than that of class A beta-lactamases
      (k2/K, >104 M-1 . s-1). In addition, we determined the structure of TLA-3 and
      that of TLA-3 complexed with avibactam or OP0595 at resolutions of 1.6, 1.6, and
      2.0 A, respectively. TLA-3 contains an inverted Omega loop and an extended loop
      between the beta5 and beta6 strands (insertion after Ser237), which appear only
      in PER-type class A beta-lactamases. These structures might favor the
      accommodation of cephalosporins harboring bulky R1 side chains. TLA-3 presented a
      high catalytic efficiency (kcat/Km ) against cephalosporins, including
      cephalothin, cefuroxime, and cefotaxime. Avibactam and OP0595 bound covalently to
      TLA-3 via the Ser70 residue and made contacts with residues Ser130, Thr235, and
      Ser237, which are conserved in ESBLs. Additionally, the sulfate group of the
      inhibitors formed polar contacts with amino acid residues in a positively charged
      pocket of TLA-3. Our findings provide a structural template for designing
      improved diazabicyclooctane-based inhibitors that are effective against ESBL
      producing Enterobacteriaceae.

PMID- 28739782
TI  - Coadministration of Allopurinol To Increase Antimycobacterial Efficacy of
      Pyrazinamide as Evaluated in a Whole-Blood Bactericidal Activity Model.
AB  - Coadministering pyrazinamide (PZA) with the xanthine oxidase inhibitor
      allopurinol increases systemic levels of the active metabolite, pyrazinoic acid
      (POA), but the effects on bactericidal activity against tuberculosis are unknown.
      We randomized healthy volunteers to take a single dose of PZA (either 10 or 25
      mg/kg of body weight) at the first visit and the same dose 7 days later,
      coadministered with allopurinol (100 mg daily; 2 days before to 1 day after the
      PZA dose). Blood was drawn at intervals until 48 h after each PZA dose, and drug
      levels were measured using liquid chromatography-tandem mass spectrometry. Whole
      blood bactericidal activity (WBA) was measured by inoculating blood samples with
      Mycobacterium tuberculosis and estimating the change in bacterial CFU after 72 h
      of incubation. Allopurinol increased the POA area under the concentration-time
      curve from 0 to 8 h (AUC0-8) (18.32 h . MUg/ml versus 24.63 h . MUg/ml for PZA
      alone versus PZA plus allopurinol) (P < 0.001) and its peak plasma concentration
      (Cmax) (2.81 MUg/ml versus 4.00 MUg/ml) (P < 0.001). There was no effect of
      allopurinol on mean cumulative WBA (0.01 +/- 0.02 DeltalogCFU versus 0.00 +/-
      0.02 DeltalogCFU for PZA alone versus PZA plus allopurinol) (P = 0.49). Higher
      systemic POA levels were associated with greater WBA levels (P < 0.001), but the
      relationship was evident only at low POA concentrations. The lack of an effect of
      allopurinol on WBA despite a significant increase in blood POA levels suggests
      that host-generated POA may be less effective than POA generated inside bacteria.
      Coadministration of allopurinol does not appear to be a useful strategy for
      increasing the efficacy of PZA in clinical practice. (This study has been
      registered at ClinicalTrials.gov under registration no. NCT02700347.).

PMID- 28739783
TI  - Effect of Rifampin on the Single-Dose Pharmacokinetics of Oral Cabotegravir in
      Healthy Subjects.
AB  - Drug-drug interactions between antiretroviral medications and rifampin complicate
      the treatment of HIV and tuberculosis coinfection. This study evaluated the
      effect of rifampin on the pharmacokinetics of oral cabotegravir, an integrase
      strand transfer inhibitor being investigated for long-acting treatment and
      prevention of HIV-1 infection. This was a phase I, single-center, open-label,
      fixed-sequence crossover study in healthy adults. The objective was to evaluate
      the effect of steady-state rifampin on the single-dose plasma pharmacokinetics of
      cabotegravir. Subjects received a single oral dose of cabotegravir (30 mg) on day
      1 followed by plasma sampling on days 1 to 8. Treatment with once-daily oral
      rifampin (600 mg) occurred on days 8 to 28. Subjects received a second dose of 30
      mg cabotegravir on day 21 followed by pharmacokinetic sampling on days 21 to 28.
      Fifteen subjects were enrolled and completed the study. Rifampin decreased the
      cabotegravir area under the concentration-time curve from 0 h to infinity and the
      half-life by 59% and 57%, respectively, whereas oral clearance was increased 2.4
      fold. The maximum concentration of cabotegravir in plasma was unaffected by
      coadministration with rifampin. All adverse events were mild in severity, with
      chromaturia attributed to rifampin observed in all subjects. Rifampin induction
      of cabotegravir metabolism resulted in increased cabotegravir oral clearance and
      significantly decreased cabotegravir exposures. Rifampin is expected to increase
      cabotegravir clearance following long-acting injectable administration.
      Concomitant administration of rifampin with oral and long-acting formulations of
      cabotegravir is not recommended currently without further study. (This study has
      been registered at ClinicalTrials.gov under registration no. NCT02411435.).

PMID- 28739784
TI  - Assessment of Bactericidal Drug Activity and Treatment Outcome in a Mouse
      Tuberculosis Model Using a Clinical Beijing Strain.
AB  - Mycobacterium tuberculosis Beijing strains are associated with lower treatment
      success rates in tuberculosis (TB) patients. In contrast, laboratory strains such
      as H37Rv are often used in preclinical tuberculosis models. Therefore, we
      explored the impact of using a clinical Beijing strain on treatment outcome in
      our mouse tuberculosis model. Additionally, the predictive value of bactericidal
      activity on treatment outcome was assessed. BALB/c mice were infected with a
      Beijing strain and treated with one of 10 different combinations of conventional
      anti-TB drugs. Bactericidal activity was assessed by determining reductions in
      mycobacterial load after 7, 14, and 28 days and after 2, 3, and 6 months of
      treatment. Treatment outcome was evaluated after a 6-month treatment course and
      was based on lung culture status 3 months posttreatment. None of the anti-TB drug
      regimens tested could achieve 100% treatment success. Treatment outcome depended
      critically on rifampin. Four non-rifampin-containing regimens showed 0% treatment
      success compared to success rates between 81 and 95% for six rifampin-containing
      regimens. Bactericidal activity was predictive only for treatment outcome after 3
      months of treatment. Our data advocate the use of multiple mycobacterial strains,
      including a Beijing strain, to increase the translational value of mouse TB
      models evaluating treatment outcome. Additionally, our findings support the
      notion that bactericidal activity in the first 2 months of treatment, as measured
      in clinical phase IIa/b trials, has limited predictive value for tuberculosis
      treatment outcome, thus emphasizing the need for better parameters to guide
      future phase IIII trials.

PMID- 28739785
TI  - Emergence of mcr-1 in Raoultella ornithinolytica and Escherichia coli Isolates
      from Retail Vegetables in China.
AB  - The presence of mcr-1 among Enterobacteriaceae isolates collected from retail
      vegetables in China between 2015 and 2016 was investigated. Two Raoultella
      ornithinolytica and seven Escherichia coli strains recovered from lettuce and
      tomato samples were identified as MCR-1-producers. Similar to isolates from
      animals and humans, the mcr-1 gene was located on the IncHI2/ST3, IncI2, or IncX4
      plasmids. The presence of MCR-1-producing organisms in ready-to-eat food samples
      represents a serious risk for human health.

PMID- 28739786
TI  - Benzoxazoles, Phthalazinones, and Arylurea-Based Compounds with IMP Dehydrogenase
      Independent Antibacterial Activity against Francisella tularensis.
AB  - Francisella tularensis is the causative agent of tularemia and a potential
      biowarfare agent. The virulence of F. tularensis is decreased by deletion of
      guaB, the gene encoding IMP dehydrogenase (IMPDH), suggesting that this enzyme is
      a target for antibacterial design. Here we report that F. tularensis growth is
      blocked by inhibitors of bacterial IMPDHs. Seventeen compounds from two different
      frameworks, designated the D and Q series, display antibacterial activities with
      MICs of <1 MUM. These compounds are also active against intracellular infections.
      Surprisingly, antibacterial activity does not correlate with IMPDH inhibition. In
      addition, the presence of guanine does not affect the antibacterial activity of
      most compounds, nor does the deletion of guaB These observations suggest that
      antibacterial activity derives from inhibition of another target(s). Moreover, D
      compounds display antibacterial activity only against F. tularensis, suggesting
      the presence of a unique target or uptake mechanism. A DeltaguaB mutant resistant
      to compound D73 contained a missense mutation (Gly45Cys) in nuoB, which encodes a
      subunit of bacterial complex I. Overexpression of the nuoB mutant conferred
      resistance to D73 in both wild-type and DeltaguaB strains. This strain was not
      resistant to Q compounds, suggesting that a different off-target mechanism
      operates for these compounds. Several Q compounds are also effective against
      Mycobacterium tuberculosis, in which a second target has also been implicated, in
      addition to IMPDH. The fortuitous presence of multiple targets with overlapping
      structure-activity relationships presents an intriguing opportunity for the
      development of robust antibiotics that may avoid the emergence of resistance.

PMID- 28739787
TI  - Resistance to Ceftazidime-Avibactam Is Due to Transposition of KPC in a Porin
      Deficient Strain of Klebsiella pneumoniae with Increased Efflux Activity.
AB  - Ceftazidime-avibactam is an antibiotic with activity against serine beta
      lactamases, including Klebsiella pneumoniae carbapenemase (KPC). Recently,
      reports have emerged of KPC-producing isolates resistant to this antibiotic,
      including a report of a wild-type KPC-3 producing sequence type 258 Klebsiella
      pneumoniae that was resistant to ceftazidime-avibactam. We describe a detailed
      analysis of this isolate, in the context of two other closely related KPC-3
      producing isolates, recovered from the same patient. Both isolates encoded a
      nonfunctional OmpK35, whereas we demonstrate that a novel T333N mutation in
      OmpK36, present in the ceftazidime-avibactam resistant isolate, reduced the
      activity of this porin and impacted ceftazidime-avibactam susceptibility. In
      addition, we demonstrate that the increased expression of blaKPC-3 and blaSHV-12
      observed in the ceftazidime-avibactam-resistant isolate was due to transposition
      of the Tn4401 transposon harboring blaKPC-3 into a second plasmid, pIncX3, which
      also harbored blaSHV-12, ultimately resulting in a higher copy number of blaKPC-3
      in the resistant isolate. pIncX3 plasmid from the ceftazidime-avibactam resistant
      isolate, conjugated into a OmpK35/36-deficient K. pneumoniae background that
      harbored a mutation to the ramR regulator of the acrAB efflux operon recreated
      the ceftazidime-avibactam-resistant MIC of 32 MUg/ml, confirming that this
      constellation of mutations is responsible for the resistance phenotype.

PMID- 28739788
TI  - Systematic Therapeutic Drug Monitoring for Linezolid: Variability and Clinical
      Impact.
AB  - Linezolid serum trough (Cmin) and peak (Cmax) levels were determined
      prospectively in 90 patients. Adequate exposure was defined as a Cmin of 2 to 8
      mg/liter. Therapy was empirical (73.3%) or targeted (26.7%). Wide interindividual
      variability in linezolid Cmin levels was recorded (0.1 to 25.2 MUg/ml). Overall,
      65.5% of the patients had out-of-range, 41.1% had subtherapeutic, and 24.4% had
      supratherapeutic trough levels. We did not find a correlation between abnormal
      levels and adverse events, in-hospital mortality, or overall poor outcome.

PMID- 28739789
TI  - Contribution of the TetB Efflux Pump to Minocycline Susceptibility among
      Carbapenem-Resistant Acinetobacter baumannii Strains.

PMID- 28739790
TI  - A Cationic Polymer That Shows High Antifungal Activity against Diverse Human
      Pathogens.
AB  - Invasive fungal diseases are generally difficult to treat and often fatal. The
      therapeutic agents available to treat fungi are limited, and there is a critical
      need for new agents to combat these deadly infections. Antifungal compound
      development has been hindered by the challenge of creating agents that are highly
      active against fungal pathogens but not toxic to the host. Host defense peptides
      (HDPs) are produced by eukaryotes as a component of the innate immune response to
      pathogens and have served as inspiration for the development of many new
      antibacterial compounds. HDP mimics, however, have largely failed to exhibit
      potent and selective antifungal activity. Here, we present an HDP-like nylon-3
      copolymer that is effective against diverse fungi while displaying only mild to
      moderate toxicity toward mammalian cells. This polymer is active on its own and
      in synergy with existing antifungal drugs against multiple species of Candida and
      Cryptococcus, reaching levels of efficacy comparable to those of the clinical
      agents amphotericin B and fluconazole in some cases. In addition, the polymer
      acts synergistically with azoles against different species of Aspergillus,
      including some azole-resistant strains. These findings indicate that nylon-3
      polymers are a promising lead for development of new antifungal therapeutic
      strategies.

PMID- 28739791
TI  - Protection of Hamsters from Mortality by Reducing Fecal Moxifloxacin
      Concentration with DAV131A in a Model of Moxifloxacin-Induced Clostridium
      difficile Colitis.
AB  - Lowering the gut exposure to antibiotics during treatments can prevent microbiota
      disruption. We evaluated the effects of an activated charcoal-based adsorbent,
      DAV131A, on the fecal free moxifloxacin concentration and mortality in a hamster
      model of moxifloxacin-induced Clostridium difficile infection. A total of 215
      hamsters receiving moxifloxacin subcutaneously (day 1 [D1] to D5) were orally
      infected at D3 with C. difficile spores. They received various doses (0 to 1,800
      mg/kg of body weight/day) and schedules (twice a day [BID] or three times a day
      [TID]) of DAV131A (D1 to D8). Moxifloxacin concentrations and C. difficile counts
      were determined at D3, and mortality was determined at D12 We compared mortality
      rates, moxifloxacin concentrations, and C. difficile counts according to DAV131A
      regimen and modeled the links between DAV131A regimen, moxifloxacin
      concentration, and mortality. All hamsters that received no DAV131A died, but
      none of those that received 1,800 mg/kg/day died. Significant dose-dependent
      relationships between DAV131A dose and (i) mortality, (ii) moxifloxacin
      concentration, and (iii) C. difficile count were evidenced. Mathematical modeling
      suggested that (i) lowering the moxifloxacin concentration at D3, which was 58
      MUg/g (95% confidence interval [CI] = 50 to 66 MUg/g) without DAV131A, to 17
      MUg/g (14 to 21 MUg/g) would reduce mortality by 90%; and (ii) this would be
      achieved with a daily DAV131A dose of 703 mg/kg (596 to 809 mg/kg). In this model
      of C. difficile infection, DAV131A reduced mortality in a dose-dependent manner
      by decreasing the fecal free moxifloxacin concentration.

PMID- 28739792
TI  - Transfersomal Phage Cocktail Is an Effective Treatment against Methicillin
      Resistant Staphylococcus aureus-Mediated Skin and Soft Tissue Infections.
AB  - The emergence of drug resistance has rekindled interest in phage therapy as an
      alternative treatment option; its potency, safety, and proven efficacy are worth
      noting. However, phage therapy still suffers from issues of poor stability,
      narrow spectra, and poor pharmacokinetic profiles. Therefore, it is essential to
      look into the use of drug delivery systems for efficient delivery of lytic phages
      in vivo The present study evaluated the use of nanostructured lipid-based
      carriers, i.e., transfersomes, as transdermal delivery systems for encapsulating
      a methicillin-resistant Staphylococcus aureus (MRSA) phage cocktail. Furthermore,
      the therapeutic potential of the encapsulated phage cocktail in resolving
      experimental soft tissue infections in rats was studied. Results from in vitro
      stability and in vivo phage titer experiments indicated that the transfersome
      entrapped phage cocktail showed better persistence and stability than did free
      phages. Rats treated with the transfersome-entrapped phage cocktail resolved the
      experimental thigh infections within a period of 7 days, unlike the 20-day period
      required for untreated animals. The findings of the present study support the use
      of transfersomes as delivery agents to enhance the stability and in vivo
      persistence of the encapsulated phages. In addition, this study highlights the
      advantages offered by transfersome-encapsulated phages in providing better
      therapeutic options than free phages for treating skin and soft tissue
      infections. The transfersome-entrapped phage cocktail was able to protect all
      test animals (with no deaths) even when administered with a delay of 12 h
      postinfection, unlike free phages, thus making this treatment option more
      suitable for clinical settings.

PMID- 28739793
TI  - Oxidative Stress Response Tips the Balance in Aspergillus terreus Amphotericin B
      Resistance.
AB  - In this study, we characterize the impact of antioxidative enzymes in
      amphotericin B (AmB)-resistant (ATR) and rare AmB-susceptible (ATS) clinical
      Aspergillus terreus isolates. We elucidate expression profiles of superoxide
      dismutase (SOD)- and catalase (CAT)-encoding genes, enzymatic activities of SODs,
      and superoxide anion production and signaling pathways involved in the oxidative
      stress response (OSR) in ATS and ATR strains under AmB treatment conditions. We
      show that ATR strains possess almost doubled basal SOD activity compared to that
      of ATS strains and that ATR strains exhibit an enhanced OSR, with significantly
      higher sod2 mRNA levels and significantly increased cat transcripts in ATR
      strains upon AmB treatment. In particular, inhibition of SOD and CAT proteins
      renders resistant isolates considerably susceptible to the drug in vitro In
      conclusion, this study shows that SODs and CATs are crucial for AmB resistance in
      A. terreus and that targeting the OSR might offer new treatment perspectives for
      resistant species.

PMID- 28739794
TI  - Population Pharmacokinetics of AZD-5847 in Adults with Pulmonary Tuberculosis.
AB  - AZD-5847 is a new oxazolidinone derivative under development for the treatment of
      tuberculosis (TB). Here we describe the population pharmacokinetics (PK) of AZD
      5847 in patients with tuberculosis based on a recently completed phase II study.
      The study included 60 patients with drug-susceptible TB. Patients were randomized
      to four dosages (500 mg once daily, 1,200 mg once daily, 500 mg twice daily, and
      800 mg twice daily). Patients were intensively sampled on days 1 and 14. AZD-5847
      pharmacokinetics were best described with a two-compartment model with lag time
      (Tlag) for absorption. AZD-5847 bioavailability was nonlinear and plateaued at
      800 mg. We performed deterministic simulation to compare the PK/pharmacodynamics
      (PD) of AZD-5847, linezolid, and sutezolid. AZD-5847 PK/PD in terms of both area
      under the concentration-time curve for the free, unbound fraction (fAUC)/MIC and
      time the free concentration was above the MIC (fT>MIC) were less favorable than
      those for linezolid and sutezolid. This could help explain the poor bactericidal
      activity of AZD-5847 in the recent phase II study.

PMID- 28739795
TI  - Clinical Characteristics and Treatment Outcomes of Patients with Acquired
      Macrolide-Resistant Mycobacterium abscessus Lung Disease.
AB  - Macrolide antibiotics are mainstays in the treatment of lung disease due to the
      Mycobacterium abscessus complex. Although previous studies have reported
      development of acquired macrolide resistance in this species, limited data are
      available on the outcomes of lung disease due to macrolide-resistant
      Mycobacterium abscessus subsp. abscessus This study evaluated the clinical
      features, treatment outcomes, and molecular characteristics of macrolide
      resistant isolates of M. abscessus subsp. abscessus We performed a retrospective
      review of medical records and genetic analysis of clinical isolates from 13
      patients who had acquired macrolide-resistant M. abscessus subsp. abscessus lung
      disease between November 2006 and March 2016. Eleven (85%) patients had the
      nodular bronchiectatic form of the disease, and two (15%) patients had the
      fibrocavitary form. When acquired macrolide resistance was detected, 10 (77%)
      patients were on antibiotic therapy for M. abscessus subsp. abscessus, and three
      (23%) patients were on therapy for lung disease due to other nontuberculous
      mycobacteria. The median treatment duration after detecting resistance was 24.0
      months (interquartile range, 16.0 to 43.0 months). Treatment outcomes were poor,
      and final sputum culture conversion was achieved in only one (8%) patient, after
      resectional surgery. All 13 clinical isolates demonstrated point mutations at
      position 2058 (n = 10) or 2059 (n = 3) of the 23S rRNA gene, which resulted in
      acquired macrolide resistance. This study indicates that treatment outcomes are
      very poor after the development of acquired macrolide resistance in patients with
      M. abscessus subsp. abscessus lung disease. Thus, more effective measures are
      needed to prevent development and effectively treat macrolide-resistant M.
      abscessus subsp. abscessus lung disease.

PMID- 28739796
TI  - Multicenter, International Study of MIC/MEC Distributions for Definition of
      Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular
      Methods.
AB  - Clinical and Laboratory Standards Institute (CLSI) conditions for testing the
      susceptibilities of pathogenic Sporothrix species to antifungal agents are based
      on a collaborative study that evaluated five clinically relevant isolates of
      Sporothrixschenckii sensu lato and some antifungal agents. With the advent of
      molecular identification, there are two basic needs: to confirm the suitability
      of these testing conditions for all agents and Sporothrix species and to
      establish species-specific epidemiologic cutoff values (ECVs) or breakpoints
      (BPs) for the species. We collected available CLSI MICs/minimal effective
      concentrations (MECs) of amphotericin B, five triazoles, terbinafine,
      flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S.
      brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates.
      Data were obtained in 17 independent laboratories (Australia, Europe, India,
      South Africa, and South and North America) using conidial inoculum suspensions
      and 48 to 72 h of incubation at 35 degrees C. Sufficient and suitable data (modal
      MICs within 2-fold concentrations) allowed the proposal of the following ECVs for
      S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 MUg/ml;
      itraconazole, 2 and 2 MUg/ml; posaconazole, 2 and 2 MUg/ml; and voriconazole, 64
      and 32 MUg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and
      0.12 MUg/ml, respectively. Insufficient or unsuitable data precluded the
      calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs
      for S. schenckii, as well as ECVs for S. globosa and S. mexicana These ECVs could
      aid the clinician in identifying potentially resistant isolates (non-wild type)
      less likely to respond to therapy.

PMID- 28739798
TI  - Patient care is at risk from inadequate handovers, GMC finds.

PMID- 28739797
TI  - Unraveling Drug Penetration of Echinocandin Antifungals at the Site of Infection
      in an Intra-abdominal Abscess Model.
AB  - Intra-abdominal candidiasis (IAC) is a prominent invasive fungal infection
      associated with high mortality. Prompt antifungal therapy and source control are
      crucial for successful treatment. Echinocandin antifungal drugs are first-line
      agents; however, their clinical effectiveness is highly variable, with known
      potential for breakthrough resistance, and little is known about drug exposure at
      the site of infection. Using matrix-assisted desorption ionization mass
      spectrometry imaging technology, we investigated the spatial and quantitative
      distribution in tissue lesions for two echinocandin drugs, micafungin and CD101,
      in a clinically relevant IAC mouse model. Drug accumulation within lesions was
      observed with both drugs at their humanized therapeutic doses. CD101, but not
      micafungin, accumulated in lesions at levels above the mutant prevention
      concentration of the infecting strain. These findings indicate that current
      echinocandin drugs are limited by penetration at the site of infection and have
      implications for clinical outcomes and emergence of resistance in patients with
      IAC.

PMID- 28739799
TI  - LGR5 receptor promotes cell-cell adhesion in stem cells and colon cancer cells
      via the IQGAP1-Rac1 pathway.
AB  - Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a bona fide
      marker of adult stem cells in several epithelial tissues, most notably in the
      intestinal crypts, and is highly up-regulated in many colorectal, hepatocellular,
      and ovarian cancers. LGR5 activation by R-spondin (RSPO) ligands potentiates
      Wnt/beta-catenin signaling in vitro; however, deletion of LGR5 in stem cells has
      little or no effect on Wnt/beta-catenin signaling or cell proliferation in vivo
      Remarkably, modulation of LGR5 expression has a major impact on the actin
      cytoskeletal structure and cell adhesion in the absence of RSPO stimulation, but
      the molecular mechanism is unclear. Here, we show that LGR5 interacts with IQ
      motif-containing GTPase-activating protein 1 (IQGAP1), an effector of Rac1/CDC42
      GTPases, in the regulation of actin cytoskeleton dynamics and cell-cell adhesion.
      Specifically, LGR5 decreased levels of IQGAP1 phosphorylation at Ser-1441/1443,
      leading to increased binding of Rac1 to IQGAP1 and thus higher levels of cortical
      F-actin and enhanced cell-cell adhesion. LGR5 ablation in colon cancer cells and
      crypt stem cells resulted in loss of cortical F-actin, reduced cell-cell
      adhesion, and disrupted localization of adhesion-associated proteins. No evidence
      of LGR5 coupling to any of the four major subtypes of heterotrimeric G proteins
      was found. These findings suggest that LGR5 primarily functions via the IQGAP1
      Rac1 pathway to strengthen cell-cell adhesion in normal adult crypt stem cells
      and colon cancer cells.

PMID- 28739800
TI  - Cell-free production of a functional oligomeric form of a Chlamydia major outer
      membrane protein (MOMP) for vaccine development.
AB  - Chlamydia is a prevalent sexually transmitted disease that infects more than 100
      million people worldwide. Although most individuals infected with Chlamydia
      trachomatis are initially asymptomatic, symptoms can arise if left undiagnosed.
      Long-term infection can result in debilitating conditions such as pelvic
      inflammatory disease, infertility, and blindness. Chlamydia infection, therefore,
      constitutes a significant public health threat, underscoring the need for a
      Chlamydia-specific vaccine. Chlamydia strains express a major outer-membrane
      protein (MOMP) that has been shown to be an effective vaccine antigen. However,
      approaches to produce a functional recombinant MOMP protein for vaccine
      development are limited by poor solubility, low yield, and protein misfolding.
      Here, we used an Escherichia coli-based cell-free system to express a MOMP
      protein from the mouse-specific species Chlamydia muridarum (MoPn-MOMP or mMOMP).
      The codon-optimized mMOMP gene was co-translated with Delta49apolipoprotein A1
      (Delta49ApoA1), a truncated version of mouse ApoA1 in which the N-terminal 49
      amino acids were removed. This co-translation process produced mMOMP supported
      within a telodendrimer nanolipoprotein particle (mMOMP-tNLP). The cell-free
      expressed mMOMP-tNLPs contain mMOMP multimers similar to the native MOMP protein.
      This cell-free process produced on average 1.5 mg of purified, water-soluble
      mMOMP-tNLP complex in a 1-ml cell-free reaction. The mMOMP-tNLP particle also
      accommodated the co-localization of CpG oligodeoxynucleotide 1826, a single
      stranded synthetic DNA adjuvant, eliciting an enhanced humoral immune response in
      vaccinated mice. Using our mMOMP-tNLP formulation, we demonstrate a unique
      approach to solubilizing and administering membrane-bound proteins for future
      vaccine development. This method can be applied to other previously difficult-to
      obtain antigens while maintaining full functionality and immunogenicity.

PMID- 28739801
TI  - Sustained O-GlcNAcylation reprograms mitochondrial function to regulate energy
      metabolism.
AB  - Dysfunctional mitochondria and generation of reactive oxygen species (ROS)
      promote chronic diseases, which have spurred interest in the molecular mechanisms
      underlying these conditions. Previously, we have demonstrated that disruption of
      post-translational modification of proteins with beta-linked N-acetylglucosamine
      (O-GlcNAcylation) via overexpression of the O-GlcNAc-regulating enzymes O-GlcNAc
      transferase (OGT) or O-GlcNAcase (OGA) impairs mitochondrial function. Here, we
      report that sustained alterations in O-GlcNAcylation either by pharmacological or
      genetic manipulation also alter metabolic function. Sustained O-GlcNAc elevation
      in SH-SY5Y neuroblastoma cells increased OGA expression and reduced cellular
      respiration and ROS generation. Cells with elevated O-GlcNAc levels had elongated
      mitochondria and increased mitochondrial membrane potential, and RNA-sequencing
      analysis indicated transcriptome reprogramming and down-regulation of the NRF2
      mediated antioxidant response. Sustained O-GlcNAcylation in mouse brain and liver
      validated the metabolic phenotypes observed in the cells, and OGT knockdown in
      the liver elevated ROS levels, impaired respiration, and increased the NRF2
      antioxidant response. Moreover, elevated O-GlcNAc levels promoted weight loss and
      lowered respiration in mice and skewed the mice toward carbohydrate-dependent
      metabolism as determined by indirect calorimetry. In summary, sustained elevation
      in O-GlcNAcylation coupled with increased OGA expression reprograms energy
      metabolism, a finding that has potential implications for the etiology,
      development, and management of metabolic diseases.

PMID- 28739802
TI  - TGF-beta1 regulates the expression and transcriptional activity of TAZ protein
      via a Smad3-independent, myocardin-related transcription factor-mediated
      mechanism.
AB  - Hippo pathway transcriptional coactivators TAZ and YAP and the TGF-beta1
      (TGFbeta) effector Smad3 regulate a common set of genes, can physically interact,
      and exhibit multilevel cross-talk regulating cell fate-determining and fibrogenic
      pathways. However, a key aspect of this cross-talk, TGFbeta-mediated regulation
      of TAZ or YAP expression, remains uncharacterized. Here, we show that TGFbeta
      induces robust TAZ but not YAP protein expression in both mesenchymal and
      epithelial cells. TAZ levels, and to a lesser extent YAP levels, also increased
      during experimental kidney fibrosis. Pharmacological or genetic inhibition of
      Smad3 did not prevent the TGFbeta-induced TAZ up-regulation, indicating that this
      canonical pathway is dispensable. In contrast, inhibition of p38 MAPK, its
      downstream effector MK2 (e.g. by the clinically approved antifibrotic
      pirferidone), or Akt suppressed the TGFbeta-induced TAZ expression. Moreover,
      TGFbeta elevated TAZ mRNA in a p38-dependent manner. Myocardin-related
      transcription factor (MRTF) was a central mediator of this effect, as MRTF
      silencing/inhibition abolished the TGFbeta-induced TAZ expression. MRTF
      overexpression drove the TAZ promoter in a CC(A/T-rich)6GG (CArG) box-dependent
      manner and induced TAZ protein expression. TGFbeta did not act by promoting
      nuclear MRTF translocation; instead, it triggered p38- and MK2-mediated, Nox4
      promoted MRTF phosphorylation and activation. Functionally, higher TAZ levels
      increased TAZ/TEAD-dependent transcription and primed cells for enhanced TAZ
      activity upon a second stimulus (i.e. sphingosine 1-phosphate) that induced
      nuclear TAZ translocation. In conclusion, our results uncover an important aspect
      of the cross-talk between TGFbeta and Hippo signaling, showing that TGFbeta
      induces TAZ via a Smad3-independent, p38- and MRTF-mediated and yet MRTF
      translocation-independent mechanism.

PMID- 28739803
TI  - Chromatin-remodeling SWI/SNF complex regulates coenzyme Q6 synthesis and a
      metabolic shift to respiration in yeast.
AB  - Despite its relatively streamlined genome, there are many important examples of
      regulated RNA splicing in Saccharomyces cerevisiae Here, we report a role for the
      chromatin remodeler SWI/SNF in respiration, partially via the regulation of
      splicing. We find that a nutrient-dependent decrease in Snf2 leads to an increase
      in splicing of the PTC7 transcript. The spliced PTC7 transcript encodes a
      mitochondrial phosphatase regulator of biosynthesis of coenzyme Q6 (ubiquinone or
      CoQ6) and a mitochondrial redox-active lipid essential for electron and proton
      transport in respiration. Increased splicing of PTC7 increases CoQ6 levels. The
      increase in PTC7 splicing occurs at least in part due to down-regulation of
      ribosomal protein gene expression, leading to the redistribution of spliceosomes
      from this abundant class of intron-containing RNAs to otherwise poorly spliced
      transcripts. In contrast, a protein encoded by the nonspliced isoform of PTC7
      represses CoQ6 biosynthesis. Taken together, these findings uncover a link
      between Snf2 expression and the splicing of PTC7 and establish a previously
      unknown role for the SWI/SNF complex in the transition of yeast cells from
      fermentative to respiratory modes of metabolism.

PMID- 28739804
TI  - Role of the disulfide bond in stabilizing and folding of the fimbrial protein
      DraE from uropathogenic Escherichia coli.
AB  - Dr fimbriae are homopolymeric adhesive organelles of uropathogenic Escherichia
      coli composed of DraE subunits, responsible for the attachment to host cells.
      These structures are characterized by enormously high stability resulting from
      the structural properties of an Ig-like fold of DraE. One feature of DraE and
      other fimbrial subunits that makes them peculiar among Ig-like domain-containing
      proteins is a conserved disulfide bond that joins their A and B strands. Here, we
      investigated how this disulfide bond affects the stability and folding/unfolding
      pathway of DraE. We found that the disulfide bond stabilizes self-complemented
      DraE (DraE-sc) by ~50 kJ mol-1 in an exclusively thermodynamic manner, i.e. by
      lowering the free energy of the native state and with almost no effect on the
      free energy of the transition state. This finding was confirmed by experimentally
      determined folding and unfolding rate constants of DraE-sc and a disulfide bond
      lacking DraE-sc variant. Although the folding of both proteins exhibited similar
      kinetics, the unfolding rate constant changed upon deletion of the disulfide bond
      by 10 orders of magnitude, from ~10-17 s-1 to 10-7 s-1 Molecular simulations
      revealed that unfolding of the disulfide bond-lacking variant is initiated by
      strands A or G and that disulfide bond-mediated joining of strand A to the core
      strand B cooperatively stabilizes the whole protein. We also show that the
      disulfide bond in DraE is recognized by the DraB chaperone, indicating a
      mechanism that precludes the incorporation of less stable, non-oxidized DraE
      forms into the fimbriae.

PMID- 28739806
TI  - Cochrane corner: long-term hormone therapy for perimenopausal and postmenopausal
      women.

PMID- 28739805
TI  - Functional insights into the mode of DNA and ligand binding of the TetR family
      regulator TylP from Streptomyces fradiae.
AB  - Tetracycline repressors (TetRs) modulate multidrug efflux pathways in several
      pathogenic bacteria. In Streptomyces, they additionally regulate secondary
      metabolic pathways like antibiotic production. For instance, in the antibiotic
      producer Streptomyces fradiae, a layered network of TetRs regulates the levels of
      the commercially important antibiotic tylosin, with TylP occupying the top of
      this cascading network. TetRs exist in two functional states, the DNA-bound and
      the ligand-bound form, which are allosterically regulated. Here, to develop
      deeper insights into the factors that govern allostery, the crystal structure of
      TylP was solved to a resolution of 2.3 A. The structure revealed that TylP
      possesses several unique features; notably, it harbors a unique C-terminal helix
      loop extension that spans the entire length of the structure. This anchor
      connects the DNA-binding domain (DBD) with the ligand-binding domain (LBD) via a
      mix of positively charged and hydrogen-bonding interactions. Supporting EMSA
      studies with a series of DeltaC truncated versions show that a systematic
      deletion of this region results in complete loss of DNA binding. The structure
      additionally revealed that TylP is markedly different in the orientation of its
      DBD and LBD architecture and the dimeric geometry from its hypothesized
      Streptomyces homologue CprB, which is a gamma-butyrolactone regulator. Rather,
      TylP is closer in structural design to macrolide-binding TetRs found in
      pathogens. Supporting molecular dynamic studies suggested that TylP binds a
      macrolide intermediate in the tylosin pathway. Collectively, the structure along
      with corroborating biochemical studies provided insights into the novel mode of
      regulation of TetRs in antibiotic-producing organisms.

PMID- 28739807
TI  - Organisation of care for pregnancy in patients with congenital heart disease.
AB  - Improvements in surgery have resulted in more women with repaired congenital
      heart disease (CHD) surviving to adulthood. Women with CHD, who wish to embark on
      pregnancy require prepregnancy counselling. This consultation should cover
      several issues such as the long-term prognosis of the mother, fertility and
      miscarriage rates, recurrence risk of CHD in the baby, drug therapy during
      pregnancy, estimated maternal risk and outcome, expected fetal outcomes and plans
      for pregnancy. Prenatal genetic testing is available for those patients with an
      identified genetic defect using pregestational diagnosis or prenatal diagnosis
      chorionic villus sampling or amniocentesis. Centralisation of care is needed for
      high-risk patients. Finally, currently there are no recommendations addressing
      the issue of the delivery. It is crucial that a dedicated plan for delivery
      should be available for all cardiac patients. The maternal mortality in low
      income to middle-income countries is 14 times higher than in high-income
      countries and needs additional aspects and dedicated care.

PMID- 28739808
TI  - Experiences of HIV postexposure prophylaxis (PEP) among highly exposed men who
      have sex with men (MSM).
AB  - OBJECTIVES: HIV postexposure prophylaxis (PEP) is indicated after sexual exposure
      with high risk of transmission. Men who have sex with men (MSM) are the main
      target of PEP. The aim of our study was to investigate the experience and
      shortcomings of PEP among people with a high risk of HIV exposure. DESIGN AND
      METHODS: Subjects with ongoing follow-up for HIV infection and PEP history were
      selected for the qualitative study. Semistructured interviews were conducted at
      the patients' homes. They were audio-recorded, transcribed and deidentified
      before data analysis, double coding and thematic analysis with an inductive
      approach. RESULTS: Twenty-three patients were eligible for the qualitative study.
      Thirteen interviews were carried out. All patients were 20-60-year-old MSM. The
      median time between PEP and HIV diagnosis was 3.3 years (interquartile range
      (IQR)25-75=0.9-4.9). Many participants reported negative PEP experiences: awkward
      access to the PEP clinic, uneasiness and shame in the hospital setting,
      unpleasant interaction and moral disapprobation from the medical staff, treatment
      intolerance and prevention messages that were 'inconsistent with real life'
      CONCLUSION: Our data highlight PEP management failures among its target
      population that may have compromised any subsequent attempts to seek out PEP.
      Practitioners should be more aware of MSM sexual contexts and practices. PEP
      consultations should provide the opportunity to discuss prevention strategies
      with highly exposed HIV-negative subjects, which may include pre-exposure
      prophylaxis.

PMID- 28739809
TI  - Genomic Medicine in Cardiovascular Fellowship Training.

PMID- 28739810
TI  - Aldosterone in Advancing Age: Don't Shoot the Messenger.

PMID- 28739811
TI  - Calcitonin Gene-Related Peptide Receptor Agonism: A Double-Edged Sword?

PMID- 28739813
TI  - Highlights From the Circulation Family of Journals.

PMID- 28739812
TI  - Transcatheter Therapy for Mitral Regurgitation Clinical Challenges and Potential
      Solutions.
AB  - Severe mitral regurgitation is a common and complex disease that is associated
      with an adverse prognosis. For decades, surgical treatment has been the standard
      of care. Recently, multiple technologies for transcatheter mitral therapy have
      emerged, with the potential for both repair and replacement in patients with
      native mitral regurgitation. Transcatheter mitral technologies have potential as
      solutions for unmet clinical needs. Further rigorous clinical studies are needed
      to determine their efficacy and safety, as well as the appropriate patient
      candidates. These evaluations will help to define the role of transcatheter
      mitral therapy as a potentially exciting new strategy to improve the lives of
      patients with mitral regurgitation.

PMID- 28739814
TI  - Health Resource Implications of Heart Failure Hospitalizations in Younger
      Patients Compared With Older Patients.

PMID- 28739815
TI  - Letter by Smiseth and Nagueh et al Regarding Article, "Role of Diastolic Stress
      Testing in the Evaluation for Heart Failure With Preserved Ejection Fraction: A
      Simultaneous Invasive-Echocardiographic Study".

PMID- 28739816
TI  - Response by Obokata and Borlaug to Letter Regarding Article, "Role of Diastolic
      Stress Testing in the Evaluation for Heart Failure With Preserved Ejection
      Fraction: A Simultaneous Invasive-Echocardiographic Study".

PMID- 28739817
TI  - Letter by Koh Regarding Article, "Genetic Obesity and the Risk of Atrial
      Fibrillation: Causal Estimates from Mendelian Randomization".

PMID- 28739818
TI  - Response by Chatterjee et al to Letter Regarding Article, "Genetic Obesity and
      the Risk of Atrial Fibrillation: Causal Estimates From Mendelian Randomization".

PMID- 28739819
TI  - Leaf Photosynthetic Parameters Related to Biomass Accumulation in a Global Rice
      Diversity Survey.
AB  - Mining natural variations is a major approach to identify new options to improve
      crop light use efficiency. So far, successes in identifying photosynthetic
      parameters positively related to crop biomass accumulation through this approach
      are scarce, possibly due to the earlier emphasis on properties related to leaf
      instead of canopy photosynthetic efficiency. This study aims to uncover rice
      (Oryza sativa) natural variations to identify leaf physiological parameters that
      are highly correlated with biomass accumulation, a surrogate of canopy
      photosynthesis. To do this, we systematically investigated 14 photosynthetic
      parameters and four morphological traits in a rice population, which consists of
      204 U.S. Department of Agriculture-curated minicore accessions collected globally
      and 11 elite Chinese rice cultivars in both Beijing and Shanghai. To identify key
      components responsible for the variance of biomass accumulation, we applied a
      stepwise feature-selection approach based on linear regression models. Although
      there are large variations in photosynthetic parameters measured in different
      environments, we observed that photosynthetic rate under low light (Alow) was
      highly related to biomass accumulation and also exhibited high genomic
      inheritability in both environments, suggesting its great potential to be used as
      a target for future rice breeding programs. Large variations in Alow among modern
      rice cultivars further suggest the great potential of using this parameter in
      contemporary rice breeding for the improvement of biomass and, hence, yield
      potential.

PMID- 28739820
TI  - Efficient Plastid Transformation in Arabidopsis.
AB  - Plastid transformation is routine in tobacco (Nicotiana tabacum) but 100-fold
      less frequent in Arabidopsis (Arabidopsis thaliana), preventing its use in
      plastid biology. A recent study revealed that null mutations in ACC2, encoding a
      plastid-targeted acetyl-coenzyme A carboxylase, cause hypersensitivity to
      spectinomycin. We hypothesized that plastid transformation efficiency should
      increase in the acc2 background, because when ACC2 is absent, fatty acid
      biosynthesis becomes dependent on translation of the plastid-encoded ACC beta
      carboxylase subunit. We bombarded ACC2-defective Arabidopsis leaves with a vector
      carrying a selectable spectinomycin resistance (aadA) gene and gfp, encoding the
      green fluorescence protein GFP. Spectinomycin-resistant clones were identified as
      green cell clusters on a spectinomycin medium. Plastid transformation was
      confirmed by GFP accumulation from the second open reading frame of a
      polycistronic messenger RNA, which would not be translated in the cytoplasm. We
      obtained one to two plastid transformation events per bombarded sample in
      spectinomycin-hypersensitive Slavice and Columbia acc2 knockout backgrounds, an
      approximately 100-fold enhanced plastid transformation frequency. Slavice and
      Columbia are accessions in which plant regeneration is uncharacterized or
      difficult to obtain. A practical system for Arabidopsis plastid transformation
      will be obtained by creating an ACC2 null background in a regenerable Arabidopsis
      accession. The recognition that the duplicated ACCase in Arabidopsis is an
      impediment to plastid transformation provides a rational template to implement
      plastid transformation in related recalcitrant crops.

PMID- 28739821
TI  - Dynamic Changes in Plant Nuclear Organization in Response to Environmental and
      Developmental Signals.

PMID- 28739822
TI  - Stress-responsive HILPDA is necessary for thermoregulation during fasting.
AB  - Hypoxia-inducible lipid droplet-associated protein (HILPDA) has been shown to
      localize to lipid droplets in nutrient-responsive cell types such as hepatocytes
      and adipocytes. However, its role in the control of whole-body homeostasis is not
      known. We sought to measure cell-intrinsic and systemic stress responses in a
      mouse strain harboring whole-body Hilpda deficiency. We generated a genetically
      engineered mouse model of whole-body HILPDA deficiency by replacing the coding
      Hilpda exon with luciferase. We subjected the knockout animals to environmental
      stresses and measured whole-animal metabolic and behavioral parameters. Brown
      adipocyte precursors were isolated and differentiated in vitro to quantify the
      impact of HILPDA ablation in lipid storage and mobilization in these cells.
      HILPDA-knockout animals are viable and fertile, but show reduced ambulatory
      activity and oxygen consumption at regular housing conditions. Acclimatization at
      thermoneutral conditions abolished the phenotypic differences observed at 22
      degrees C. When fasted, HILPDA KO mice are unable to maintain body temperature
      and become hypothermic at 22 degrees C, without apparent abnormalities in blood
      chemistry parameters or tissue triglyceride content. HILPDA expression was
      upregulated during adipocyte differentiation and activation in vitro; however, it
      was not required for lipid droplet formation in brown adipocytes. We conclude
      that HILPDA is necessary for efficient fuel utilization suggesting a homeostatic
      role for Hilpda in sub-optimal environments.

PMID- 28739823
TI  - Interleukin-17A Aggravates Middle Ear Injury Induced by Streptococcus pneumoniae
      through the p38 Mitogen-Activated Protein Kinase Signaling Pathway.
AB  - Acute otitis media (AOM) is one of the most common bacterial infectious diseases
      in children aged 2 to 7 years worldwide. We previously demonstrated that
      interleukin-17A (IL-17A) promotes an acute inflammatory response characterized by
      the influx of neutrophils into the middle ear cavity during Streptococcus
      pneumoniae-induced AOM. In general, the inflammatory response is viewed as an
      effector that frequently causes local tissue damage. However, little is known
      about the pathogenic effects of IL-17A in AOM. Here, we investigated the
      pathogenic effects of IL-17A by using wild-type (WT) and IL-17A knockout (KO)
      mouse models. The results showed that the pathogenic effects of AOM, including
      weight loss, histopathological changes, and proinflammatory cytokine production,
      were more severe in WT mice than in IL-17A KO mice, suggesting that IL-17A
      aggravates tissue damage in AOM. Furthermore, these pathogenic effects were found
      to be dependent on p38 mitogen-activated protein kinase (MAPK) and could be
      reversed in the presence of a p38 MAPK-specific inhibitor. It was also
      demonstrated that IL-17A promoted the production of neutrophil myeloperoxidase
      (MPO) through the p38 MAPK signaling pathway, which was responsible for the
      middle ear tissue injury. These data support the conclusion that IL-17A
      contributes to middle ear injury through the p38 MAPK signaling pathway.

PMID- 28739824
TI  - Epigenetic Mechanisms Regulate Innate Immunity against Uropathogenic and
      Commensal-Like Escherichia coli in the Surrogate Insect Model Galleria
      mellonella.
AB  - Innate-immunity-related genes in humans are activated during urinary tract
      infections (UTIs) caused by pathogenic strains of Escherichia coli but are
      suppressed by commensals. Epigenetic mechanisms play a pivotal role in the
      regulation of gene expression in response to environmental stimuli. To determine
      whether epigenetic mechanisms can explain the different behaviors of pathogenic
      and commensal bacteria, we infected larvae of the greater wax moth, Galleria
      mellonella, a widely used model insect host, with a uropathogenic E. coli (UPEC)
      strain that causes symptomatic UTIs in humans or a commensal-like strain that
      causes asymptomatic bacteriuria (ABU). Infection with the UPEC strain (CFT073)
      was more lethal to larvae than infection with the attenuated ABU strain (83972)
      due to the recognition of each strain by different Toll-like receptors,
      ultimately leading to differential DNA/RNA methylation and histone acetylation.
      We used next-generation sequencing and reverse transcription (RT)-PCR to
      correlate epigenetic changes with the induction of innate-immunity-related genes.
      Transcriptomic analysis of G. mellonella larvae infected with E. coli strains
      CFT073 and 83972 revealed strain-specific variations in the class and expression
      levels of genes encoding antimicrobial peptides, cytokines, and enzymes
      controlling DNA methylation and histone acetylation. Our results provide evidence
      for the differential epigenetic regulation of transcriptional reprogramming by
      UPEC and ABU strains of E. coli in G. mellonella larvae, which may be relevant to
      understanding the different behaviors of these bacterial strains in the human
      urinary tract.

PMID- 28739825
TI  - Neisseria cinerea expresses a functional factor H binding protein which is
      recognised by immune responses elicited by meningococcal vaccines.
AB  - Neisseria meningitidis is a major cause of bacterial meningitis and sepsis
      worldwide. Capsular polysaccharide vaccines are available against meningococcal
      serogroups A, C, W and Y. More recently two protein based vaccines, Bexsero(r)
      and Trumenba(r), have been licenced against meningococcal serogroup B strains;
      both vaccines contain meningococcal factor H binding protein (fHbp). fHbp is a
      surface exposed lipoprotein which binds the negative complement regulator,
      complement factor H (CFH), thereby inhibiting the alternative pathway of
      complement activation. Recent analysis of available genomes has indicated that
      some commensal Neisseria species also contain genes that potentially encode fHbp,
      although the function of these genes and how immunisation with fHbp-containing
      vaccines could affect the commensal flora have yet to be established. Here we
      show that the commensal species Neisseria cinerea expresses functional fHbp on
      its surface and is responsible for recruitment of CFH by the bacterium. N.
      cinerea fHbp binds CFH at similar affinity as meningococcal fHbp, and promotes
      survival of N. cinerea in human serum. We examined the potential impact of fHbp
      containing vaccines on N. cinerea We found that immunisation with Bexsero(r)
      elicits serum bactericidal activity against N. cinerea, which is primarily
      directed against fHbp. The shared function of fHbp in N. cinerea and N.
      meningitidis, and cross reactive responses elicited by Bexsero(r) suggest that
      the introduction of fHbp-containing vaccines has the potential to affect carriage
      of N. cinerea and other commensal species.

PMID- 28739826
TI  - Interleukin-17C in Human Helicobacter pylori Gastritis.
AB  - The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in
      many inflammatory diseases. Although IL-17A is recognized as being involved in
      the pathophysiology of Helicobacter pylori-associated diseases, the role of other
      IL-17 cytokine family members remains unclear. Microarray analysis of IL-17
      family cytokines was performed in H. pylori-infected and uninfected gastric
      biopsy specimens. IL-17C mRNA was upregulated approximately 4.5-fold in H. pylori
      infected gastric biopsy specimens. This was confirmed by quantitative reverse
      transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan
      and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C
      expression in H. pylori-infected gastric biopsy specimens was predominantly
      localized to epithelial and chromogranin A-positive endocrine cells. IL-17C mRNA
      levels were also significantly greater among cagA-positive than cagA-negative H.
      pylori infections (P = 0.012). In vitro studies confirmed an increase in IL-17C
      mRNA and protein levels in cells infected with cagA-positive infections compared
      to cells infected with either cagA-negative or cag pathogenicity island (PAI)
      mutant. Chemical inhibition of IkappaB kinase (IKK), mitogen-activated protein
      extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK)
      inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition
      had no effect on IL-17C protein secretion. In conclusion, H. pylori infection was
      associated with a significant increase in IL-17C expression in human gastric
      mucosa. The role of IL-17C in the pathogenesis of H. pylori-induced diseases
      remains to be determined.

PMID- 28739827
TI  - Transcriptional Profiling of the Chicken Tracheal Response to Virulent Mycoplasma
      gallisepticum Strain Rlow.
AB  - Mycoplasma gallisepticum, the primary etiologic agent of chronic respiratory
      disease (CRD) in poultry, leads to prolonged recruitment and activation of
      inflammatory cells in the respiratory mucosa. This is consistent with the current
      model of immune dysregulation that ostensibly allows the organism to evade
      clearance mechanisms and establish chronic infection. To date, studies using
      quantitative reverse transcription-PCR (qRT-PCR) and microarrays have shown a
      significant transient upregulation of cytokines and chemokines from tracheal
      epithelial cells (TECs) in vitro and tracheal tissue ex vivo in response to
      virulent strain Rlow that contributes to the infiltration of inflammatory cells
      into the tracheal mucosa. To expand upon these experiments, RNA was isolated from
      tracheas of 20 chickens infected with M. gallisepticum Rlow and 20 mock-infected
      animals at days 1, 3, 5, and 7 postinoculation, and samples were analyzed for
      differential gene expression using Illumina RNA sequencing. A rapid host response
      was observed 24 h postinfection, with over 2,500 significantly differentially
      expressed genes on day 3, the peak of infection. Many of these genes have immune
      related functions involved in signaling pathways, including Toll-like receptor
      (TLR), mitogen-activated protein kinase, Jak-STAT, and the nucleotide
      oligomerization domain-like receptor pathways. Of interest was the increased
      expression of numerous cell surface receptors, including TLR4 and TLR15, which
      may contribute to the production of cytokines. Metabolic pathways were also
      activated on days 1 and 3 postinfection, ostensibly due to epithelial cell
      distress that occurs upon infection. Early perturbations in tissue-wide gene
      expression, as observed here, may underpin a profound immune dysregulation,
      setting the stage for disease manifestations characteristic of M. gallisepticum
      infection.

PMID- 28739828
TI  - Mouse Bone Marrow Sca-1+ CD44+ Mesenchymal Stem Cells Kill Avirulent Mycobacteria
      but Not Mycobacterium tuberculosis through Modulation of Cathelicidin Expression
      via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway.
AB  - Mycobacterium tuberculosis primarily infects lung macrophages. However, a recent
      study showed that M. tuberculosis also infects and persists in a dormant form
      inside bone marrow mesenchymal stem cells (BM-MSCs) even after successful
      antibiotic therapy. However, the mechanism(s) by which M. tuberculosis survives
      in BM-MSCs is still not known. Like macrophages, BM-MSCs do not contain a well
      defined endocytic pathway, which is known to play a central role in the clearance
      of internalized mycobacteria. Here, we studied the fate of virulent and avirulent
      mycobacteria in Sca-1+ CD44+ BM-MSCs. We found that BM-MSCs were able to kill
      avirulent Mycobacterium smegmatis and Mycobacterium bovis BCG but not the
      pathogenic species M. tuberculosis Further mechanistic studies revealed that
      pathogenic M. tuberculosis dampens the antibacterial response of BM-MSCs by
      downregulating the expression of the cationic antimicrobial peptide cathelicidin.
      In contrast, avirulent mycobacteria were effectively killed by inducing the Toll
      like receptor 2/4 (TLR2/4) pathway-dependent expression of cathelicidin, while
      small interfering RNA (siRNA)-mediated cathelicidin silencing increased the
      survival of M. bovis BCG in BM-MSCs. We also showed that M. bovis BCG infection
      caused increased expression levels of MyD88, phospho-interleukin-1 receptor
      associated kinase 4 (pIRAK-4), and the p38 mitogen-activated protein kinase
      (MAPK) signaling pathway. Further downstream investigations demonstrated that
      IRAK-4-p38 activation increased the nuclear translocation of NF-kappaB, which
      subsequently induced the expression of cathelicidin and the cytokine interleukin
      1beta (IL-1beta), resulting in the decreased survival of M. bovis BCG. On the
      other hand, inhibition of TLR2/4, pIRAK-4, p38, and NF-kappaB nuclear
      translocation decreased cathelicidin and IL-1beta expression levels and therefore
      increased the survival of avirulent mycobacteria. This is the first report that
      demonstrates that virulent mycobacteria manipulate the TLR2/4-MyD88-IRAK-4-p38-NF
      kappaB-Camp-IL-1beta pathway to survive inside bone marrow stem cells.

PMID- 28739829
TI  - Inherent Oxidative Stress in the Lewis Rat Is Associated with Resistance to
      Toxoplasmosis.
AB  - The course of Toxoplasma gondii infection in rats closely resembles that in
      humans. However, compared to the Brown Norway (BN) rat, the Lewis (LEW) rat is
      extremely resistant to T. gondii infection. Thus, we performed RNA sequencing
      analysis of the LEW rat versus the BN rat, with or without T. gondii infection,
      in order to unravel molecular factors directing robust and rapid early T. gondii
      killing mechanisms in the LEW rat. We found that compared to the uninfected BN
      rat, the uninfected LEW rat has inherently higher transcript levels of cytochrome
      enzymes (Cyp2d3, Cyp2d5, and Cybrd1, which catalyze generation of reactive oxygen
      species [ROS]), with concomitant higher levels of ROS. Interestingly, despite
      having higher levels of ROS, the LEW rat had lower transcript levels for
      antioxidant enzymes (lactoperoxidase, microsomal glutathione S-transferase 2 and
      3, glutathione S-transferase peroxidase kappa 1, and glutathione peroxidase) than
      the BN rat, suggesting that the LEW rat maintains cellular oxidative stress that
      it tolerates. Corroboratively, we found that scavenging of superoxide anion by
      Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) decreased the refractoriness
      of LEW rat peritoneal cells to T. gondii infection, resulting in proliferation of
      parasites in LEW rat peritoneal cells which, in turn, led to augmented cell death
      in the infected cells. Together, our results indicate that the LEW rat maintains
      inherent cellular oxidative stress that contributes to resistance to invading T.
      gondii, and they thus unveil new avenues for developing therapeutic agents
      targeting induction of host cell oxidative stress as a mechanism for killing T.
      gondii.

PMID- 28739830
TI  - Complement C3 as a Prompt for Human Macrophage Death during Infection with
      Francisella tularensis Strain SCHU S4.
AB  - Tularemia is caused by the Gram-negative bacterial pathogen Francisella
      tularensis Infection of macrophages and their subsequent death are believed to
      play important roles in the progression of disease. Because complement is a
      particularly effective opsonin for Francisella, we asked whether complement
      dependent uptake of F. tularensis strain SCHU S4 affects the survival of primary
      human macrophages during infection. Complement component C3 was found to be an
      essential opsonin in human serum not only for greatly increased uptake of SCHU S4
      but also for the induction of macrophage death. Single-cell analysis also
      revealed that macrophage death did not require a high intracellular bacterial
      burden. In the presence of C3, macrophage death was observed at 24 h
      postinfection in a quarter of the macrophages that contained only 1 to 5
      bacterial cells. Macrophages infected in the absence of C3 rarely underwent cell
      death, even when they contained large numbers of bacteria. The need for C3, but
      not extensive replication of the pathogen, was confirmed by infections with SCHU
      S4 DeltapurMCD, a mutant capable of phagosome escape but of only limited
      cytosolic replication. C3-dependent Francisella uptake alone was insufficient to
      induce macrophage death, as evidenced by the failure of the phagosome escape
      deficient mutant SCHU S4 DeltafevR to induce cell death despite opsonization with
      C3. Together, these findings indicate that recognition of C3-opsonized F.
      tularensis, but not extensive cytosolic replication, plays an important role in
      regulating macrophage viability during intracellular infections with type A F.
      tularensis.

PMID- 28739831
TI  - Neutrophils Are Central to Antibody-Mediated Protection against Genital
      Chlamydia.
AB  - Determining the effector populations involved in humoral protection against
      genital chlamydia infection is crucial to development of an effective chlamydial
      vaccine. Antibody has been implicated in protection studies in multiple animal
      models, and we previously showed that the passive transfer of immune serum alone
      does not confer immunity in the mouse. Using the Chlamydia muridarum model of
      genital infection, we demonstrate a protective role for both Chlamydia-specific
      immunoglobulin G (IgG) and polymorphonuclear neutrophils and show the importance
      of an antibody/effector cell interaction in mediating humoral immunity. While
      neutrophils were found to contribute significantly to antibody-mediated
      protection in vivo, natural killer (NK) cells were dispensable for protective
      immunity. Furthermore, gamma interferon (IFN-gamma)-stimulated primary peritoneal
      neutrophils (PPNs) killed chlamydiae in vitro in an antibody-dependent manner.
      The results from this study support the view that an IFN-gamma-activated effector
      cell population cooperates with antibody to protect against genital chlamydia and
      establish neutrophils as a key effector cell in this response.

PMID- 28739832
TI  - Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic
      Stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke
      Study) Post Hoc Analysis.
AB  - BACKGROUND AND PURPOSE: Renal dysfunction (RD) is associated with poor prognosis
      after stroke. We assessed the effects of RD on outcomes and interaction with low-
      versus standard-dose alteplase in a post hoc subgroup analysis of the ENCHANTED
      (Enhanced Control of Hypertension and Thrombolysis Stroke Study). METHODS: A
      total of 3220 thrombolysis-eligible patients with acute ischemic stroke (mean
      age, 66.5 years; 37.8% women) were randomly assigned to low-dose (0.6 mg/kg) or
      standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom
      onset. Six hundred and fifty-nine (19.8%) patients had moderate-to-severe RD
      (estimated glomerular filtration rate, <60 mL/min per 1.73 m2) at baseline. The
      impact of RD on death or disability (modified Rankin Scale scores, 2-6) at 90
      days, and symptomatic intracerebral hemorrhage, was assessed in logistic
      regression models. RESULTS: Compared with patients with normal renal function
      (>90 mL/min per 1.73 m2), those with severe RD (<30 mL/min per 1.73 m2) had
      increased mortality (adjusted odds ratio, 2.07; 95% confidence interval, 0.89
      4.82; P=0.04 for trend); every 10 mL/min per 1.73 m2 lower estimated glomerular
      filtration rate was associated with an adjusted 9% increased odds of death from
      thrombolysis-treated acute ischemic stroke. There was no significant association
      with modified Rankin Scale scores 2 to 6 (adjusted odds ratio, 1.03; 95%
      confidence interval, 0.62-1.70; P=0.81 for trend), modified Rankin Scale 3 to 6
      (adjusted odds ratio, 1.20; 95% confidence interval, 0.72-2.01; P=0.44 for
      trend), or symptomatic intracerebral hemorrhage, or any heterogeneity in
      comparative treatment effects between low-dose and standard-dose alteplase by RD
      grades. CONCLUSIONS: RD is associated with increased mortality but not disability
      or symptomatic intracerebral hemorrhage in thrombolysis-eligible and treated
      acute ischemic stroke patients. Uncertainty persists as to whether low-dose
      alteplase confers benefits over standard-dose alteplase in acute ischemic stroke
      patients with RD. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01422616.

PMID- 28739833
TI  - Risk Factors of Sudden Death From Subarachnoid Hemorrhage.
AB  - BACKGROUND AND PURPOSE: One in every 4 subarachnoid hemorrhage (SAH) patients
      dies suddenly outside hospital, but most SAH risk factor studies focus on
      hospitalized patients. We studied the differences in risk factors between
      hospitalized SAH and sudden-death SAH patients. METHODS: The population-based
      FINRISK study cohort of 65 521 individuals was followed up for 1.52 million
      person-years. The Cox proportional hazards model calculated hazard ratios (HRs),
      with all analyses adjusted for known SAH risk factors, marital status, and
      socioeconomic status. A competing risks model analyzed differences in risk
      factors between hospitalized SAHs and sudden-death SAHs. RESULTS: We identified
      98 sudden-death SAHs and 445 hospitalized SAHs confirmed by autopsy or by
      standard SAH diagnostics. Increase by 5 cigarettes smoked per day elevated sudden
      death SAH risk (HR, 1.28; 95% confidence interval [CI], 1.17-1.39) more than
      hospitalized SAH risk (HR, 1.19; 95% CI, 1.13-1.24; P=0.05 for difference). Per
      SD (21.4 mm Hg) increase, systolic blood pressure elevated risk of sudden-death
      SAH (HR, 1.34; 95% CI, 1.09-1.65) more than risk for hospitalized SAH (HR, 1.25;
      (95% CI, 1.12-1.38; P=0.05 for difference). Participants living without a partner
      were at elevated risk of sudden-death SAH (HR, 2.09; 95% CI, 1.33-3.28) but not
      of hospitalized SAH. No sudden-death SAHs occurred in normotensive never smokers
      aged <50 years. CONCLUSIONS: Sudden-death SAH risk seems to be highest among
      those individuals with the most adverse risk factor profiles and among those who
      live without a partner, whereas it is rare among normotensive never smokers aged
      <50 years.

PMID- 28739835
TI  - Training load and structure-specific load: applications for sport injury
      causality and data analyses.

PMID- 28739834
TI  - Change in physical activity from adolescence to early adulthood: a systematic
      review and meta-analysis of longitudinal cohort studies.
AB  - OBJECTIVE: To systematically review and meta-analyse how physical activity (PA)
      changes from adolescence to early adulthood (13-30 years). DATA SOURCES: Seven
      electronic databases were searched: Medline, Embase, PsycInfo, SCOPUS, ASSIA,
      SPORTdiscus and Web of Science. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:
      English-language, longitudinal studies (from 01/1980 to 01/2017) assessing PA
      >=twice, with the mean age of >=1 measurement in adolescence (13-19 years) and
      >=1 in young adulthood (16-30 years) were included. Where possible, data were
      converted to moderate-to-vigorous physical activity (MVPA) min/day, and meta
      analyses were conducted between weighted mean differences (WMDs) in adolescence
      and adulthood. Heterogeneity was explored using meta-regression. RESULTS: Of 67
      included studies, 49 were eligible for meta-analysis. PA was lower during
      adulthood than adolescence WMD (95% CI) -5.2 (-7.3 to -3.1) min/day MVPA over
      mean (SD) 3.4 (2.6) years; heterogeneity was high (I2 >99.0%), and no predictors
      explained this variation (all p>0.05). When we restricted analysis to studies
      with data for males (n=29) and females (n=30) separately, there were slightly
      larger declines in WMD (-6.5 (-10.6 to -2.3) and -5.5 (-8.4 to -2.6) min/day
      MVPA) (both I2 >99.0%). For studies with accelerometer data (n=9), the decline
      was -7.4 (-11.6 to -3.1) and longer follow-up indicated more of a decline in WMD
      (95% CI) (-1.9 (-3.6 to -0.2) min/day MVPA), explaining 27.0% of between-study
      variation. Of 18 studies not eligible for meta-analysis, nine statistically
      tested change over time: seven showed a decline and two showed no change.
      CONCLUSION: PA declines modestly between adolescence and young adulthood. More
      objective longitudinal PA data (eg, accelerometry) over this transition would be
      valuable, as would investigating how PA change is associated with contemporaneous
      social transitions to better inform PA promotion interventions. REGISTRATION:
      PROSPERO ref:CRD42015030114.

PMID- 28739836
TI  - Psychological impact of electrocardiogram screening in National Collegiate
      Athletic Association athletes.
AB  - PURPOSE: Determine the psychological impact of false-positive ECG screening in
      National Collegiate Athletic Association (NCAA) athletes. METHODS: Athletes
      representing seven NCAA institutions received a standardised history, physical
      examination and ECG interpreted using the 2013 Seattle Criteria. Assessments of
      health attitudes, anxiety and impact of screening on sport were conducted using
      validated prescreen and postscreen measurements. RESULTS: 1192 student-athletes
      participated (55.4% male, median age 19 years, 80.4% Caucasian). 96.8% of
      athletes had a normal cardiovascular screen, 2.9% had a false-positive ECG and
      0.3% were diagnosed with a serious cardiac condition. Prior to screening, 4.5%
      worried about potentially harbouring cardiac disease and 70.1% preferred knowing
      about an underlying condition, rather than play sports without this knowledge.
      There was no difference in anxiety described by athletes with a normal versus
      false-positive screen (p=0.369). Reported anxiety levels during screening also
      did not differ when analysed by different gender, race, division of play or
      sport. Athletes with normal and false-positive screens had similar levels of
      satisfaction (p=0.714) and would recommend ECG screening to other athletes at
      similar rates (p=0.322). Compared with athletes with a normal screen, athletes
      with false-positive results also reported feeling safer during competition
      (p>0.01). In contrast, athletes with false-positive screens were more concerned
      about the possibility of sports disqualification (p<0.001) and the potential for
      developing a future cardiac condition (p<0.001). CONCLUSIONS: Athletes with a
      false-positive ECG do not experience more anxiety than athletes with a normal
      screen but do express increased concern regarding sports disqualification and the
      development of a cardiac disorder. These findings do not justify avoiding
      advanced cardiovascular screening protocols. Further understanding of athlete
      experiences could better prepare the practising physician to counsel athletes
      with an abnormal ECG.

PMID- 28739837
TI  - Mortality and causes of death among homeless in Finland: a 10-year follow-up
      study.
AB  - BACKGROUND: Homelessness is associated with increased mortality, and some
      predictors of mortality have been previously identified. We examined the overall
      and cause-specific mortality among homeless men in Helsinki and the associations
      of social background and health service use with mortality. METHODS: To assess
      cause-specific mortality in a competing risks framework, we performed a register
      based, case-control study of 617 homeless men and an age-matched control group of
      1240 men from the general population that were followed for 10 years between 2004
      and 2014. Cox proportional hazards model was used to calculate HR for death and a
      competing risks model to calculate sub-HRs (sHR) for cause-specific death.
      RESULTS: During the follow-up, 45.0% of the homeless died compared with 10.5% of
      controls (HR 5.38, 95% CI 4.39 to 6.59). The risk of death was particularly
      elevated for the homeless aged<=50 years (HR 10.3, 95% CI 7.0 to 15.2). External
      causes caused 34% of the deaths (sHR 11.2, 95% CI 6.8 to 18.2), but also deaths
      from medical causes were common (sHR 3.6, 95% CI 2.9 to 4.6). Age and somatic
      hospitalisation were significant predictors of death both among homeless and
      controls. Educational attainment, marital status, employment and psychiatric
      hospitalisation were significant predictors of mortality among the controls, but
      not among the homeless. CONCLUSIONS: Homelessness is associated with a fivefold
      mortality compared with the controls, and especially homeless aged <=50 years
      have an increased risk of death. Being homeless eliminates the protective effects
      of marriage, employment and education on mortality risk.

PMID- 28739838
TI  - Unravelling migrants' health paradoxes: a transdisciplinary research agenda.
AB  - The Social Determinants of Health literature has consistently found that a higher
      socioeconomic status is associated with better health outcomes even after
      adjusting for traditional risk factors. However, research findings in the field
      of Migrants' Health suggest that the socioeconomic/health gradient does not
      always behave as expected for migrants and their descendants. The mismatch of
      findings in these two long-standing parallel research traditions is exemplified
      by frequent reports of paradoxical findings in the scientific literature: the
      healthy migrant paradox, the ethnic density paradox and the diminishing returns
      paradox. This paper outlines a transdisciplinary research agenda to elucidate the
      social processes that underpin these disconcerting findings and calls for a shift
      from a pathogenic deficit model that sees migrants as a burden to their
      reconceptualisation as actively engaged citizens in search of solutions. Amidst a
      severe refugee crisis, fears of terrorist attacks and political capitalisation of
      these tragedies to foster antimigrant sentiments, this is urgently needed.

PMID- 28739839
TI  - Dog ownership supports the maintenance of physical activity during poor weather
      in older English adults: cross-sectional results from the EPIC Norfolk cohort.
AB  - BACKGROUND: Dog ownership has been suggested to encourage physical activity in
      older adults and may enhance resilience to poor environmental conditions. This
      study investigates the role of dog ownership and walking as a means of supporting
      the maintenance of physical activity in older adults during periods of inclement
      weather. METHODS: The analysis used data from the European Prospective
      Investigation into Cancer and Nutrition Norfolk cohort. Daily physical activity
      (counts per minute) and minutes of sedentary behaviour were measured using
      accelerometers over 7 days. Three types of environmental conditions, day length,
      precipitation and maximum temperature, were date matched with daily physical
      activity. A multilevel first-order autoregressive time-series model quantified
      the moderating effect of self-reported dog ownership and walking on the
      association between physical activity and weather factors. RESULTS: Among the
      3123 participants, 18% reported having a dog in their households and two-thirds
      of dog owners walked their dogs at least once a day. Regular dog walkers were
      more active and less sedentary on days with the poorest conditions than non-dog
      owners were on the days with the best conditions. In days with the worst
      conditions, those who walked their dogs had 20% higher activity levels than non
      dog owners and spent 30 min/day less sedentary. CONCLUSION: Those who walked dogs
      were consistently more physically active than those who did not regardless of
      environmental conditions. These large differences suggest that dog walking, where
      appropriate, can be a component of interventions to support physical activity in
      older adults.

PMID- 28739840
TI  - Mitochondrial Sirtuins in cardiometabolic diseases.
AB  - Mitochondria are heterogeneous and essentially contribute to cellular functions
      and tissue homeostasis. Mitochondrial dysfunction compromises overall cell
      functioning, tissue damage, and diseases. The advances in mitochondrion biology
      increase our understanding of mitochondrial dynamics, bioenergetics, and redox
      homeostasis, and subsequently, their functions in tissue homeostasis and
      diseases, including cardiometabolic diseases (CMDs). The functions of
      mitochondria mainly rely on the enzymes in their matrix. Sirtuins are a family of
      NAD+-dependent deacylases and ADP-ribosyltransferases. Three members of the
      Sirtuin family (SIRT3, SIRT4, and SIRT5) are located in the mitochondrion. These
      mitochondrial Sirtuins regulate energy and redox metabolism as well as
      mitochondrial dynamics in the mitochondrial matrix and are involved in
      cardiovascular homeostasis and CMDs. In this review, we discuss the advances in
      our understanding of mitochondrial Sirtuins in mitochondrion biology and CMDs,
      including cardiac remodeling, pulmonary artery hypertension, and vascular
      dysfunction. The potential therapeutic strategies by targetting mitochondrial
      Sirtuins to improve mitochondrial function in CMDs are also addressed.

PMID- 28739841
TI  - The 'Goldilocks zone' of fatty acid metabolism; to ensure that the relationship
      with cardiac function is just right.
AB  - Fatty acids (FA) are the main fuel used by the healthy heart to power
      contraction, supplying 60-70% of the ATP required. FA generate more ATP per
      carbon molecule than glucose, but require more oxygen to produce the ATP, making
      them a more energy dense but less oxygen efficient fuel compared with glucose.
      The pathways involved in myocardial FA metabolism are regulated at various
      subcellular levels, and can be divided into sarcolemmal FA uptake, cytosolic
      activation and storage, mitochondrial uptake and beta-oxidation. An understanding
      of the critical involvement of each of these steps has been amassed from genetic
      mouse models, where forcing the heart to metabolize too much or too little fat
      was accompanied by cardiac contractile dysfunction and hypertrophy. In cardiac
      pathologies, such as heart disease and diabetes, aberrations in FA metabolism
      occur concomitantly with changes in cardiac function. In heart failure, FA
      oxidation is decreased, correlating with systolic dysfunction and hypertrophy. In
      contrast, in type 2 diabetes, FA oxidation and triglyceride storage are
      increased, and correlate with diastolic dysfunction and insulin resistance.
      Therefore, too much FA metabolism is as detrimental as too little FA metabolism
      in these settings. Therapeutic compounds that rebalance FA metabolism may provide
      a mechanism to improve cardiac function in disease. Just like Goldilocks and her
      porridge, the heart needs to maintain FA metabolism in a zone that is 'just
      right' to support contractile function.

PMID- 28739842
TI  - New Biomarker Identified for PDAC.
AB  - A new study suggests that the protein THBS2 could lead to early detection of
      pancreatic ductal adenocarcinoma. By testing for THBS2 and another marker, CA19
      9, researchers identified blood samples from patients with the disease with 98%
      specificity and 87% sensitivity.

PMID- 28739843
TI  - Taking the Guesswork Out of Stopping TKIs.
AB  - More and more patients with chronic myeloid leukemia are discontinuing therapy
      after their cancer goes into remission, improving their quality of life and
      remaining disease-free for years. However, this strategy works only in a subset
      of patients. Researchers are attempting to refine criteria for discontinuing
      treatment, determine the manner in which therapy should be stopped, and identify
      prognostic biomarkers.

PMID- 28739844
TI  - Spreading Colon Cancer Can Bypass Lymph Nodes.
AB  - A new study uses evolutionary analysis to show that some colorectal tumor cells
      colonize the lymph nodes before metastasizing to the organs. However, the study
      finds that most metastases descend from subclones in the tumor itself.

PMID- 28739845
TI  - A national health care data network is overdue.

PMID- 28739846
TI  - Long-term stroke prevention: We can do better.

PMID- 28739848
TI  - Neurosyphilis mimicking autoimmune encephalitis in a 52-year-old man.

PMID- 28739849
TI  - Metastatic lung cancer presenting as cutaneous nodules.

PMID- 28739847
TI  - Long-term morbidity and mortality in patients without early complications after
      stroke or transient ischemic attack.
AB  - BACKGROUND: Secondary prevention after stroke and transient ischemic attack (TIA)
      has focused on high early risk of recurrence, but survivors of stroke can have
      substantial long-term morbidity and mortality. We quantified long-term morbidity
      and mortality for patients who had no early complications after stroke or TIA and
      community-based controls. METHODS: This longitudinal case-control study included
      all ambulatory or hospitalized patients with stroke or TIA (discharged from
      regional stroke centres in Ontario from 2003 to 2013) who survived for 90 days
      without recurrent stroke, myocardial infarction, all-cause admission to hospital,
      admission to an institution or death. Cases and controls were matched on age, sex
      and geographic location. The primary composite outcome was death, stroke,
      myocardial infarction, or admission to long-term or continuing care. We
      calculated 1-, 3- and 5-year rates of composite and individual outcomes and used
      cause-specific Cox regression to estimate long-term hazards for cases versus
      controls and for patients with stroke versus those with TIA. RESULTS: Among
      patients who were initially stable after stroke or TIA (n = 26 366), the hazard
      of the primary outcome was more than double at 1 year (hazard ratio [HR] 2.4, 95%
      confidence interval [CI] 2.3-2.5), 3 years (HR 2.2, 95% CI 2.1-2.3) and 5 years
      (HR 2.1, 95% CI 2.1-2.2). Hazard was highest for recurrent stroke at 1 year (HR
      6.8, 95% CI 6.1-7.5), continuing to 5 years (HR 5.1, 95% CI 4.8-5.5), and for
      admission to an institution (HR 2.1, 95% CI 1.9-2.2). Survivors of stroke had
      higher mortality and morbidity, but 31.5% (1789/5677) of patients with TIA
      experienced an adverse event within 5 years. INTERPRETATION: Patients who survive
      stroke or TIA without early complications are typically discharged from secondary
      stroke prevention services. However, these patients remain at substantial long
      term risk, particularly for recurrent stroke and admission to an institution.
      Novel approaches to prevention, potentially embedded in community or primary
      care, are required for long-term management of these initially stable but high
      risk patients.

PMID- 28739850
TI  - Cannabis prohibition harms Canada's youth.

PMID- 28739851
TI  - Cannabis use, legalization and youth health.

PMID- 28739852
TI  - 3D printing set to revolutionize medicine.

PMID- 28739853
TI  - SOGC urges national enquiry into maternal deaths.

PMID- 28739854
TI  - WHO guidelines on ethical public health surveillance.

PMID- 28739856
TI  - CKS Proteins Promote Checkpoint Recovery by Stimulating Phosphorylation of
      Treslin.
AB  - CKS proteins are small (9-kDa) polypeptides that bind to a subset of the cyclin
      dependent kinases. The two paralogs expressed in mammals, Cks1 and Cks2, share an
      overlapping function that is essential for early development. However, both
      proteins are frequently overexpressed in human malignancy. It has been shown that
      CKS protein overexpression overrides the replication stress checkpoint, promoting
      continued origin firing. This finding has led to the proposal that CKS protein
      dependent checkpoint override allows premalignant cells to evade oncogene stress
      barriers, providing a causal link to oncogenesis. Here, we provide mechanistic
      insight into how overexpression of CKS proteins promotes override of the
      replication stress checkpoint. We show that CKS proteins greatly enhance the
      ability of Cdk2 to phosphorylate the key replication initiation protein treslin
      in vitro Furthermore, stimulation of treslin phosphorylation does not occur by
      the canonical adapter mechanism demonstrated for other substrates, as cyclin
      dependent kinase (CDK) binding-defective mutants are capable of stimulating
      treslin phosphorylation. This effect is recapitulated in vivo, where silencing of
      Cks1 and Cks2 decreases treslin phosphorylation, and overexpression of wild-type
      or CDK binding-defective Cks2 prevents checkpoint-dependent dephosphorylation of
      treslin. Finally, we provide evidence that the role of CKS protein-dependent
      checkpoint override involves recovery from checkpoint-mediated arrest of DNA
      replication.

PMID- 28739857
TI  - Acylation of Superoxide Dismutase 1 (SOD1) at K122 Governs SOD1-Mediated
      Inhibition of Mitochondrial Respiration.
AB  - In this study, we employed proteomics to identify mechanisms of posttranslational
      regulation on cell survival signaling proteins. We focused on Cu-Zn superoxide
      dismutase (SOD1), which protects cells from oxidative stress. We found that
      acylation of K122 on SOD1, while not impacting SOD1 catalytic activity,
      suppressed the ability of SOD1 to inhibit mitochondrial metabolism at respiratory
      complex I. We found that deacylase depletion increased K122 acylation on SOD1,
      which blocked the suppression of respiration in a K122-dependent manner. In
      addition, we found that acyl-mimicking mutations at K122 decreased SOD1
      accumulation in mitochondria, initially hinting that SOD1 may inhibit respiration
      directly within the intermembrane space (IMS). However, surprisingly, we found
      that forcing the K122 acyl mutants into the mitochondria with an IMS-targeting
      tag did not recover their ability to suppress respiration. Moreover, we found
      that suppressing or boosting respiration levels toggled SOD1 in or out of the
      mitochondria, respectively. These findings place SOD1-mediated inhibition of
      respiration upstream of its mitochondrial localization. Lastly, deletion-rescue
      experiments show that a respiration-defective mutant of SOD1 is also impaired in
      its ability to rescue cells from toxicity caused by SOD1 deletion. Together,
      these data suggest a previously unknown interplay between SOD1 acylation,
      metabolic regulation, and SOD1-mediated cell survival.

PMID- 28739858
TI  - How to prepare cytological samples for molecular testing.
AB  - This review is focused on the challenges in standardising and optimising
      molecular testing workflow in cytopathology. Although cytological samples yield
      optimal quality DNA, whose minimal amounts in most cases suffice even for
      multigene mutational profiling, the success of molecular testing is strongly
      dependent on standardised preanalytical protocols for maximising DNA yield and
      quality. Sample cytopreparation influences, even more, the quality of RNA and
      consequently the potential success of reverse transcription-PCR. Here, the
      educational and technical involvement of the cytopathologist as a relevant
      component of a multidisciplinary team, in the issues related to test request,
      specimen collection, fixation, processing, staining, tumour fraction enrichment,
      DNA quality/quantity assessment and storage conditions is discussed. In addition,
      the specific sample requirements related to more recent technological
      developments are examined, underlining the modern role of the cytopathologist,
      whose continuous education is crucial to meet the opportunities of molecular
      medicine.

PMID- 28739860
TI  - Current and Future Use of Robotic Devices to Perform Percutaneous Coronary
      Interventions: A Review.

PMID- 28739859
TI  - Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors.
AB  - Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on
      Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here, we
      present the first whole-genome data on the mutational signatures of AFB1 exposure
      from a total of >40,000 mutations in four experimental systems: two different
      human cell lines, in liver tumors in wild-type mice, and in mice that carried a
      hepatitis B surface antigen transgene-this to model the multiplicative effects of
      aflatoxin exposure and hepatitis B in causing HCC. AFB1 mutational signatures
      from all four experimental systems were remarkably similar. We integrated the
      experimental mutational signatures with data from newly sequenced HCCs from
      Qidong County, China, a region of well-studied aflatoxin exposure. This indicated
      that COSMIC mutational signature 24, previously hypothesized to stem from
      aflatoxin exposure, indeed likely represents AFB1 exposure, possibly combined
      with other exposures. Among published somatic mutation data, we found evidence of
      AFB1 exposure in 0.7% of HCCs treated in North America, 1% of HCCs from Japan,
      but 16% of HCCs from Hong Kong. Thus, aflatoxin exposure apparently remains a
      substantial public health issue in some areas. This aspect of our study
      exemplifies the promise of future widespread resequencing of tumor genomes in
      providing new insights into the contribution of mutagenic exposures to cancer
      incidence.

PMID- 28739861
TI  - Correlates of Dementia and Mild Cognitive Impairment in Patients With Atrial
      Fibrillation: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC
      NCS).
AB  - BACKGROUND: Atrial fibrillation (AF) has been associated with faster cognitive
      decline and increased dementia risk. Factors associated with dementia in patients
      with AF have been seldom studied. METHODS AND RESULTS: We studied 6432
      individuals from the ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive
      Study). In 2011 to 2013, participants underwent a physical exam,
      echocardiography, detailed cognitive assessments, and a subset, brain magnetic
      resonance imaging. Dementia and mild cognitive impairment (MCI), as well as
      etiology of MCI/dementia, Alzheimer's disease-related or vascular, were
      adjudicated by an expert panel. AF was defined by study ECGs and past
      hospitalizations. We used logistic regression to estimate odds ratios and 95% CI
      of MCI/dementia by AF status and to assess cross-sectional correlates of
      MCI/dementia in patients with AF. Among 6432 participants, 611 (9.5%) had
      prevalent AF. AF was associated with increased odds of dementia and MCI (odds
      ratio, 95% CI, 2.25, 1.64-3.10, and 1.28, 1.04-1.56, respectively). Prevalence of
      Alzheimer's disease-related MCI/dementia and vascular MCI/dementia were higher in
      participants with AF than without AF (odds ratio, 95% CI, 1.29, 1.04-1.61, and
      1.50, 0.99-2.25, respectively). In multivariable analyses, older age, lower body
      mass index, diabetes mellitus, stroke, and APOE genotype were associated with
      dementia prevalence in participants with AF. In models evaluating MCI/dementia
      subtypes, diabetes mellitus was associated with Alzheimer's disease-related
      MCI/dementia, whereas male sex and stroke were risk factors for vascular
      MCI/dementia. CONCLUSIONS: In a large, community-based study, AF was associated
      with higher prevalence of MCI and dementia. Controlling cardiometabolic risk
      factors is a potential target for prevention of adverse cognitive outcomes in AF
      patients.

PMID- 28739862
TI  - Switch From Fetal to Adult SCN5A Isoform in Human Induced Pluripotent Stem Cell
      Derived Cardiomyocytes Unmasks the Cellular Phenotype of a Conduction Disease
      Causing Mutation.
AB  - BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC
      CMs) can recapitulate features of ion channel mutations causing inherited rhythm
      disease. However, the lack of maturity of these cells is considered a significant
      limitation of the model. Prolonged culture of hiPSC-CMs promotes maturation of
      these cells. We studied the electrophysiological effects of the I230T mutation in
      the sodium channel gene SCN5A in hiPSC-CMs generated from a homozygous
      (I230Thomo) and a heterozygous (I230Thet) individual from a family with recessive
      cardiac conduction disease. Since the I230T mutation occurs in the
      developmentally regulated "adult" isoform of SCN5A, we investigated the
      relationship between the expression fraction of the adult SCN5A isoform and the
      electrophysiological phenotype at different time points in culture. METHODS AND
      RESULTS: After a culture period of 20 days, sodium current (INa) was mildly
      reduced in I230Thomo hiPSC-CMs compared with control hiPSC-CMs, while I230Thet
      hiPSC-CMs displayed no reduction in INa. This coincided with a relatively high
      expression fraction of the "fetal" SCN5A isoform compared with the adult isoform
      as measured by quantitative polymerase chain reaction. Following prolonged
      culture to 66 days, the fraction of adult SCN5A isoform increased; this was
      paralleled by a marked decrease in INa in I230Thomo hiPSC-CMs, in line with the
      severe clinical phenotype in homozygous patients. At this time in culture,
      I230Thet hiPSC-CMs displayed an intermediate loss of INa, compatible with a gene
      dosage effect. CONCLUSIONS: Prolonged culture of hiPSC-CMs leads to an increased
      expression fraction of the adult sodium channel isoform. This new aspect of
      electrophysiological immaturity should be taken into account in studies that
      focus on the effects of SCN5A mutations in hiPSC-CMs.

PMID- 28739864
TI  - Late-onset Tay-Sachs disease.
AB  - We discuss the assessment and differential diagnoses of a young adult Hungarian
      man with a 1-year history of a progressive and symmetric amyotrophic lateral
      sclerosis-like syndrome, along with irregular action tremor and stimulus
      sensitive myoclonus of the arms. MR scan of the brain showed isolated cerebellar
      atrophy and formal neuropsychometric testing identified significant subclinical
      deficits in attention, processing speed and memory. We suspected a form of GM2
      gangliosidosis, and white cell enzyme analysis showed markedly reduced enzymatic
      activity of beta-hexosaminidase A. Genetic testing subsequently revealed two
      heterozygous pathogenic mutations in the HEXA gene (c.1499delT p.(Leu500fs) and
      c.805G>A p.(Gly269Ser)), confirming the very rare diagnosis of adult-onset Tay
      Sachs disease.

PMID- 28739865
TI  - Pyramidal versus inverse pyramidal patterns in functional limb weakness.

PMID- 28739866
TI  - What a neurologist should know about depression in Parkinson's disease.
AB  - Depression is a frequent non-motor symptom of Parkinson's disease. Its prevalence
      varies widely across studies (between 2.7% and 90%); around 35% have clinically
      significant depressive symptoms. Although depression can have an immense impact
      on the quality of life of affected patients and their caregivers, depressive
      symptoms in Parkinson's disease frequently remain unrecognised and, as a result,
      remain untreated. Here we overview the diagnostic challenges and pitfalls,
      including the factors contributing to the underdiagnosis of depression. We also
      discuss current ideas on the underlying pathophysiology. Finally, we offer a
      treatment approach based on currently available evidence.

PMID- 28739863
TI  - Prognostic Impact of Peak Aortic Jet Velocity in Conservatively Managed Patients
      With Severe Aortic Stenosis: An Observation From the CURRENT AS Registry.
AB  - BACKGROUND: There are limited data regarding the risk stratification based on
      peak aortic jet velocity (Vmax) in patients with severe aortic stenosis (AS).
      METHODS AND RESULTS: Among 3815 consecutive patients with severe AS enrolled in
      the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in
      Patients With Severe Aortic Stenosis) registry, the study population consisted of
      1075 conservatively managed patients with Vmax >=4.0 m/s and left ventricular
      ejection fraction >=50%. The study patients were subdivided into 3 groups based
      on Vmax (group 1, 4.0 <= Vmax <4.5 m/s, N=550; group 2, 4.5 <= Vmax <5 m/s,
      N=279; and group 3, Vmax >=5 m/s, N=246). Cumulative 5-year incidence of AS
      related events (aortic valve-related death or heart failure hospitalization) was
      incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and
      62.8%, P<0.001; symptomatic patients; 55.7%, 60.9%, and 72.2%, P=0.008; and
      asymptomatic patients; 29.4%, 38.9%, and 47.7%, P=0.005). After adjusting for
      confounders, the excess risk of group 2 and group 3 relative to group 1 for AS
      related events remained significant (hazard ratio, 1.39; 95% CI, 1.07-1.81;
      P=0.02, and hazard ratio, 1.53; 95% CI, 1.17-2.00; P=0.002, respectively). The
      effect size of group 3 relative to group 1 for AS-related events in asymptomatic
      patients (N=479) was similar to that in symptomatic patients (N=596; hazard
      ratio, 1.59; 95% CI, 1.01-2.52; P=0.047, and hazard ratio, 1.67; 95% CI, 1.16
      2.40, P=0.008, respectively), and there was no significant overall interaction
      between the symptomatic status and the effect of the Vmax categories on AS
      related events (interaction, P=0.88). CONCLUSIONS: In conservatively managed
      severe AS patients with preserved left ventricular ejection fraction, increasing
      Vmax was associated with incrementally higher risk for AS-related events.
      However, the cumulative 5-year incidence of the AS-related events remained very
      high even in asymptomatic patients with less greater Vmax.

PMID- 28739867
TI  - Soft Tissue Sarcomas of the Extremities: Surgical Margins Can Be Close as Long as
      the Resected Tumor Has No Ink on It.
AB  - BACKGROUND: Soft tissue sarcomas (STS) arising in the extremities pose a
      therapeutic challenge due to concerns of functional morbidity. Resections with
      negative margins are the mainstay of therapy, but the prognostic significance of
      surgical margins remains controversial. The purpose of this study was to
      determine the prognostic impact of surgical margins and clear margin widths in
      patients with STS of the extremities. MATERIALS AND METHODS: We assessed the
      relationship between local recurrence-free (LRFS), disease-specific (DSS), and
      metastasis-free survival (MFS) and potential prognostic factors retrospectively
      in a consecutive series of 643 patients treated at our institution between 1996
      and 2016. Potential prognostic factors were assessed using univariate and
      multivariate analyses. RESULTS: The median follow-up time after primary diagnosis
      was 5.4 years (95% confidence interval [CI]: 4.8-6.0). The five-year estimates of
      the DSS, LRFS, and MFS rates in the entire cohort were 85.3% (95% CI: 81.6-88.3),
      65.3% (95% CI: 60.8-69.5) and 78.0% (95% CI: 74.1-81.4), respectively.
      Histological grade and the quality of surgical margins were independent
      prognostic factors of all three survival endpoints (LRFS, DSS, MFS) in
      multivariate analyses. Within the R0 subgroup, univariate and multivariate
      analyses of categorized (<=1 mm vs. 1-5 mm vs. >5 mm) and non-categorized margin
      widths revealed that close and wide negative margins led to similar outcomes.
      Adjuvant radiation improved local control independently, but not DSS and MFS.
      CONCLUSION: Microscopically negative margins were associated with better LRFS,
      DSS, and MFS regardless of whether adjuvant radiation was applied. Here, surgical
      margins can be close as long as the resected tumor has no ink on it. IMPLICATIONS
      FOR PRACTICE: In the present retrospective analysis of 643 patients with primary
      soft issue sarcomas of the extremities, surgical margins could be identified as
      independent predictors of local recurrence-free, disease-specific, and metastasis
      free survival. Given the diminished outcome of patients left with positive
      margins, surgical efforts should aim to achieve microscopically negative margins
      whenever feasible. It is noteworthy that only the quality of surgical margins,
      but not the negative margin width attained, had an influence on the prognosis.
      Our findings suggest that surgical margins can be close as long as the resected
      tumor has no ink on it.

PMID- 28739868
TI  - What's the Harm?

PMID- 28739869
TI  - The Harm in Kratom.

PMID- 28739870
TI  - Development of Palliative Care in China: A Tale of Three Cities.
AB  - BACKGROUND: China is the most populous country in the world, but access to
      palliative care is extremely limited. A better understanding of the development
      of palliative care programs in China and how they overcome the barriers to
      provide services would inform how we can further integrate palliative care into
      oncology practices in China. Here, we describe the program development and
      infrastructure of the palliative care programs at three Chinese institutions,
      using these as examples to discuss strategies to accelerate palliative care
      access for cancer patients in China. METHODS: Case study of three palliative care
      programs in Chengdu, Kunming, and Beijing. RESULTS: The three examples of
      palliative care delivery in China ranged from a comprehensive program that
      includes all major branches of palliative care in Chengdu, a program that is
      predominantly inpatient-based in Kunming, and a smaller program at an earlier
      stage of development in Beijing. Despite the numerous challenges related to the
      limited training opportunities, stigma on death and dying, and lack of resources
      and policies to support clinical practice, these programs were able to overcome
      many barriers to offer palliative care services to patients with advanced
      diseases and to advance this discipline in China through visionary leadership,
      collaboration with other countries to acquire palliative care expertise,
      committed staff members, and persistence. CONCLUSION: Palliative care is limited
      in China, although a few comprehensive programs exist. Our findings may inform
      palliative care program development in other Chinese hospitals. IMPLICATIONS FOR
      PRACTICE: With a population of 1.3 billion, China is the most populous country in
      the world, and cancer is the leading cause of death. However, only 0.7% of
      hospitals offer palliative care services, which significantly limits palliative
      care access for Chinese cancer patients. Here, we describe the program
      development and infrastructure of three palliative care programs in China, using
      these as examples to discuss how they were able to overcome various barriers to
      implement palliative care. Lessons from these programs may help to accelerate the
      progress of palliative cancer care in China.

PMID- 28739871
TI  - Cyclin-dependent kinase 1 (CDK1)-mediated mitotic phosphorylation of the
      transcriptional co-repressor Vgll4 inhibits its tumor-suppressing activity.
AB  - The Hippo pathway is an evolutionarily conserved signaling pathway that plays
      important roles in stem cell biology, tissue homeostasis, and cancer development.
      Vestigial-like 4 (Vgll4) functions as a transcriptional co-repressor in the Hippo
      Yes-associated protein (YAP) pathway. Vgll4 inhibits cell proliferation and tumor
      growth by competing with YAP for binding to TEA-domain proteins (TEADs). However,
      the mechanisms by which Vgll4 itself is regulated are unclear. Here we identified
      a mechanism that regulates Vgll4's tumor-suppressing function. We found that
      Vgll4 is phosphorylated in vitro and in vivo by cyclin-dependent kinase 1 (CDK1)
      during antimitotic drug-induced mitotic arrest and also in normal mitosis. We
      further identified Ser-58, Ser-155, Thr-159, and Ser-280 as the main mitotic
      phosphorylation sites in Vgll4. We also noted that the nonphosphorylatable mutant
      Vgll4-4A (S58A/S155A/T159A/S280A) suppressed tumorigenesis in pancreatic cancer
      cells in vitro and in vivo to a greater extent than did wild-type Vgll4,
      suggesting that mitotic phosphorylation inhibits Vgll4's tumor-suppressive
      activity. Consistent with these observations, the Vgll4-4A mutant possessed
      higher-binding affinity to TEAD1 than wild-type Vgll4. Interestingly, Vgll4 and
      Vgll4-4A markedly suppressed YAP and beta-catenin signaling activity. Together,
      these findings reveal a previously unrecognized mechanism for Vgll4 regulation in
      mitosis and its role in tumorigenesis.

PMID- 28739872
TI  - Redox-dependent dimerization of p38alpha mitogen-activated protein kinase with
      mitogen-activated protein kinase kinase 3.
AB  - The kinase p38alpha MAPK (p38alpha) plays a pivotal role in many biological
      processes. p38alpha is activated by canonical upstream kinases that phosphorylate
      the activation region. The purpose of our study was to determine whether such
      activation may depend on redox-sensing cysteines within p38alpha. p38alpha was
      activated and formed a disulfide-bound heterodimer with MAP2K3 (MKK3) in rat
      cardiomyocytes and isolated hearts exposed to H2O2 This disulfide heterodimer was
      sensitive to reduction by mercaptoethanol and was enhanced by the thioredoxin
      reductase inhibitor auranofin. We predicted that Cys-119 or Cys-162 of p38alpha,
      close to the known MKK3 docking domain, were relevant for these redox
      characteristics. The C119S mutation decreased whereas the C162S mutation
      increased the dimer formation, suggesting that these two Cys residues act as
      vicinal thiols, consistent with C119S/C162S being incapable of sensing H2O2
      Similarly, disulfide heterodimer formation was abolished in H9C2 cells expressing
      both MKK3 and p38alpha C119S/C162S and subjected to simulated ischemia and
      reperfusion. However, the p38alpha C119S/C162S mutants did not exhibit
      appreciable alteration in activating dual phosphorylation. In contrast, the anti
      inflammatory agent 10-nitro-oleic acid (NO2-OA), a component of the Mediterranean
      diet, reduced p38alpha activation and covalently modified Cys-119/Cys-162,
      probably obstructing MKK3 access. Moreover, NO2-OA reduced the dephosphorylation
      of p38alpha by hematopoietic tyrosine phosphatase (HePTP). Furthermore, steric
      obstruction of Cys-119/Cys-162 by NO2-OA pretreatment in Langendorff-perfused
      murine hearts prevented the p38-MKK3 disulfide dimer formation and attenuated
      H2O2-induced contractile dysfunction. Our findings suggest that cysteine residues
      within p38alpha act as redox sensors that can dynamically regulate the
      association between p38 and MKK3.

PMID- 28739873
TI  - Growth-incompetent monomers of human calcitonin lead to a noncanonical direct
      relationship between peptide concentration and aggregation lag time.
AB  - The role of the peptide hormone calcitonin in skeletal protection has led to its
      use as a therapeutic for osteoporosis. However, calcitonin aggregation into
      amyloid fibrils limits its therapeutic efficacy, necessitating a modification of
      calcitonin's aggregation kinetics. Here, we report a direct relationship between
      human calcitonin (hCT) concentration and aggregation lag time. This kinetic trend
      was contrary to the conventional understanding of amyloid aggregation and
      persisted over a range of aggregation conditions, as confirmed by thioflavin-T
      kinetics assays, CD spectroscopy, and transmission EM. Dynamic light scattering,
      1H NMR experiments, and seeded thioflavin-T assay results indicated that
      differences in initial peptide species contribute to this trend more than
      variations in the primary nucleus formation rate. On the basis of kinetics
      modeling results, we propose a mechanism whereby a structural conversion of hCT
      monomers is needed before incorporation into the fibril. Our kinetic mechanism
      recapitulates the experimentally observed relationship between peptide
      concentration and lag time and represents a novel mechanism in amyloid
      aggregation. Interestingly, hCT at low pH and salmon calcitonin (sCT) exhibited
      the canonical inverse relationship between concentration and lag time.
      Comparative studies of hCT and sCT with molecular dynamics simulations and CD
      indicated an increased alpha-helical structure in sCT and low-pH hCT monomers
      compared with neutral-pH hCT, suggesting that alpha-helical monomers represent a
      growth-competent species, whereas unstructured random coil monomers represent a
      growth-incompetent species. Our finding that initial monomer concentration is
      positively correlated with lag time in hCT aggregation could help inform future
      efforts for improving therapeutic applications of CT.

PMID- 28739874
TI  - The K-Ras effector p38gamma MAPK confers intrinsic resistance to tyrosine kinase
      inhibitors by stimulating EGFR transcription and EGFR dephosphorylation.
AB  - Mutations in K-Ras and epidermal growth factor receptor (EGFR) are mutually
      exclusive, but it is not known how K-Ras activation inactivates EGFR, leading to
      resistance of cancer cells to anti-EGFR therapy. Here, we report that the K-Ras
      effector p38gamma MAPK confers intrinsic resistance to small molecular tyrosine
      kinase inhibitors (TKIs) by concurrently stimulating EGFR gene transcription and
      protein dephosphorylation. We found that p38gamma increases EGFR transcription by
      c-Jun-mediated promoter binding and stimulates EGFR dephosphorylation via
      activation of protein-tyrosine phosphatase H1 (PTPH1). Silencing the p38gamma/c
      Jun/PTPH1 signaling network increased sensitivities to TKIs in K-Ras mutant cells
      in which EGFR knockdown inhibited growth. Similar results were obtained with the
      p38gamma-specific pharmacological inhibitor pirfenidone. These results indicate
      that in K-Ras mutant cancers, EGFR activity is regulated by the p38gamma/c
      Jun/PTPH1 signaling network, whose disruption may be a novel strategy to restore
      the sensitivity to TKIs.

PMID- 28739875
TI  - Impaired Transmigration of Myeloid-Derived Suppressor Cells across Human
      Sinusoidal Endothelium Is Associated with Decreased Expression of CD13.
AB  - Human monocytic myeloid-derived suppressor cells (MO-MDSCs) within the hepatic
      compartment suppress inflammation and impair immune surveillance in liver cancer.
      It is currently not known whether recruitment of MO-MDSCs from blood via hepatic
      sinusoidal endothelium (HSEC) contributes to their enrichment within the hepatic
      compartment. We compared the transmigratory potential of MO-MDSCs and monocytes
      after adhesion to hepatic endothelial monolayers in flow-based assays that mimic
      in vivo shear stress in the sinusoids. Despite comparable binding to HSEC
      monolayers, proportionally fewer MO-MDSCs underwent transendothelial migration,
      indicating that the final steps of extravasation, where actin polymerization
      plays an important role, are impaired in MO-MDSCs. In this article, we found
      reduced levels of CD13 on MO-MDSCs, which has recently been reported to control
      cell motility in monocytes, alongside reduced VLA-4 expression, an integrin
      predominantly involved in adherence to the apical side of the endothelium. CD13
      and VLA-4 blocking and activating Abs were used in flow-based adhesion assays,
      live-cell imaging of motility, and actin polymerization studies to confirm a role
      for CD13 in impaired MO-MDSC transmigration. These findings indicate that CD13
      significantly contributes to tissue infiltration by MO-MDSCs and monocytes,
      thereby contributing to the pathogenesis of hepatic inflammation.

PMID- 28739876
TI  - CXCL1 and CXCL2 Regulate NLRP3 Inflammasome Activation via G-Protein-Coupled
      Receptor CXCR2.
AB  - Inflammation is an extensively concerted process that confers protection to the
      host encountering immune insult. The major inflammatory mediators include IL-1
      family members, such as IL-1beta, and the functional activation of such molecules
      is arbitrated by their regulated cleavage brought about by components of a
      multiprotein complex called inflammasome. In this context, NLR family pyrin
      domain containing 3 (NLRP3) inflammasome activation often acts as a rate-limiting
      step in regulating critical cell-fate decisions in various inflammatory
      scenarios. In this study, we identify the G-protein-coupled receptor CXCR2
      (recognizing chemokines CXCL1 and CXCL2) as another arm feeding into the
      regulated activation of NLRP3 inflammasome in macrophages. We demonstrate that in
      vivo blocking of CXCL1 and CXCL2 can significantly reduce the Mycobacterium
      tuberculosis-induced bioactive IL-1beta production. Further, CXCL1 could amplify
      the inflammasome activation in in vivo mouse models of carrageenan-induced
      inflammation in footpads and air pouches. The mechanistic insights revealed CXCR2
      driven protein kinase C MU-dependent integrin-linked kinase to be essential for
      CXCL1-mediated activation of NLRP3 inflammasome. Blocking the activity of
      integrin-linked kinase or protein kinase C MU either by small interfering RNA
      mediated knockdown or pharmacological inhibitor compromised inflammasome
      activation and subsequent production of bioactive IL-1beta. Taken together, our
      study demonstrates CXCR2-driven activation of NLRP3 inflammasome in macrophages
      and indicates a potential host-directed therapeutic target to limit the damaging
      inflammation associated with overt production of proinflammatory IL-1beta.

PMID- 28739877
TI  - PALLD Regulates Phagocytosis by Enabling Timely Actin Polymerization and
      Depolymerization.
AB  - PALLD is an actin cross-linker supporting cellular mechanical tension. However,
      its involvement in the regulation of phagocytosis, a cellular activity essential
      for innate immunity and physiological tissue turnover, is unclear. We report that
      PALLD is highly induced along with all-trans-retinoic acid-induced maturation of
      myeloid leukemia cells, to promote Ig- or complement-opsonized phagocytosis.
      PALLD mechanistically facilitates phagocytic receptor clustering by regulating
      actin polymerization and c-Src dynamic activation during particle binding and
      early phagosome formation. PALLD is also required at the nascent phagosome to
      recruit phosphatase oculocerebrorenal syndrome of Lowe, which regulates
      phosphatidylinositol-4,5-bisphosphate hydrolysis and actin depolymerization to
      complete phagosome closure. Collectively, our results show a new function for
      PALLD as a crucial regulator of the early phase of phagocytosis by elaborating
      dynamic actin polymerization and depolymerization.

PMID- 28739878
TI  - Deconstructing the Lectin Pathway in the Pathogenesis of Experimental
      Inflammatory Arthritis: Essential Role of the Lectin Ficolin B and Mannose
      Binding Protein-Associated Serine Protease 2.
AB  - Complement plays an important role in the pathogenesis of rheumatoid arthritis.
      Although the alternative pathway (AP) is known to play a key pathogenic role in
      models of rheumatoid arthritis, the importance of the lectin pathway (LP) pattern
      recognition molecules such as ficolin (FCN) A, FCN B, and collectin (CL)-11, as
      well as the activating enzyme mannose-binding lectin-associated serine protease-2
      (MASP-2), are less well understood. We show in this article that FCN A-/- and CL
      11-/- mice are fully susceptible to collagen Ab-induced arthritis (CAIA). In
      contrast, FCN B-/- and MASP-2-/-/sMAp-/- mice are substantially protected, with
      clinical disease activity decreased significantly (p < 0.05) by 47 and 70%,
      respectively. Histopathology scores, C3, factor D, FCN B deposition, and
      infiltration of synovial macrophages and neutrophils were similarly decreased in
      FCN B-/- and MASP-2-/-/sMAp-/- mice. Our data support that FCN B plays an
      important role in the development of CAIA, likely through ligand recognition in
      the joint and MASP activation, and that MASP-2 also contributes to the
      development of CAIA, likely in a C4-independent manner. Decreased AP activity in
      the sera from FCN B-/- and MASP-2-/-/sMAp-/- mice with arthritis on adherent anti
      collagen Abs also support the hypothesis that pathogenic Abs, as well as
      additional inflammation-related ligands, are recognized by the LP and operate in
      vivo to activate complement. Finally, we also speculate that the residual disease
      seen in our studies is driven by the AP and/or the C2/C4 bypass pathway via the
      direct cleavage of C3 through an LP-dependent mechanism.

PMID- 28739879
TI  - Trypanosoma musculi Infection in Mice Critically Relies on Mannose Receptor
      Mediated Arginase Induction by a TbKHC1 Kinesin H Chain Homolog.
AB  - Arginase activity induction in macrophages is an escape mechanism developed by
      parasites to cope with the host's immune defense and benefit from increased host
      derived growth factor production. We report that arginase expression and activity
      were induced in macrophages during mouse infection by Trypanosoma musculi, a
      natural parasite of this host. This induction was reproduced in vitro by
      excreted/secreted factors of the parasite. A mAb directed to TbKHC1, an orphan
      kinesin H chain from Trypanosoma brucei, inhibited T. musculi excreted/secreted
      factor-mediated arginase induction. Anti-TbKHC1 Ab also inhibited T. musculi
      growth, both in vitro and in vivo. Induction of arginase activity and parasite
      growth involved C-type lectin receptors, because mannose injection decreased
      arginase activity induction and parasite load in vitro and in vivo. Accordingly,
      the parasite load was reduced in mice lacking mannose receptor C-type 1. The T.
      musculi KHC1 homolog showed high similarity with TbKHC1. Bioinformatics analysis
      revealed the presence of homologs of this gene in other trypanosomes, including
      pathogens for humans and animals. Host metabolism dysregulation represents an
      effective parasite mechanism to hamper the host immune response and modify host
      molecule production to favor parasite invasion and growth. Thus, this orphan
      kinesin plays an important role in promoting trypanosome infection, and its
      neutralization or the lock of its partner host molecules offers promising
      approaches to increasing resistance to infection and new developments in
      vaccination against trypanosomiasis.

PMID- 28739881
TI  - Cutting Edge: TRAF6 Mediates TLR/IL-1R Signaling-Induced Nontranscriptional
      Priming of the NLRP3 Inflammasome.
AB  - NLRP3 inflammasome activiation requires two sequential signals. The priming
      signal 1 from TLRs or cytokine receptors induces the transcription of NLRP3 and
      IL-1beta, and concomitantly promotes transcription-independent activation of
      caspase-1. The activating signal 2 can be provided by microbial products or
      danger signals. In this study we found that TRAF6 is necessary for the
      nontranscriptional priming of NLRP3 inflammasome by TLR/IL-1R derived signals.
      Deficiency of TRAF6 specifically inhibited TLR/IL-1R priming-initiated caspase-1
      cleavage, pyroptosis, and secretion of presynthesized IL-18. Mechanistically,
      TRAF6 promoted NLRP3 oligomerization as well as the interaction between NLRP3 and
      apoptosis-associated speck-like protein containing a CARD. Of note, the
      nontranscriptional priming via TRAF6 did not involve mitochondrial reactive
      oxygen species or the phosphorylation of Jnk, Erk, and Syk, whereas the ubiquitin
      E3 ligase activity of TRAF6 was required. Our findings thus extended cognition on
      the mechanism of NLRP3 inflammasome activation, and provided a novel target for
      controlling NLRP3-related diseases.

PMID- 28739880
TI  - Neoantigen Expression in Steady-State Langerhans Cells Induces CTL Tolerance.
AB  - The skin hosts a variety of dendritic cells (DCs), which act as professional APC
      to control cutaneous immunity. Langerhans cells (LCs) are the only DC subset in
      the healthy epidermis. However, due to the complexity of the skin DC network,
      their relative contribution to either immune activation or immune tolerance is
      still not entirely understood. To specifically study the function of LCs in vivo,
      without altering the DC subset composition in the skin, we have generated
      transgenic mouse models for tamoxifen-inducible de novo expression of Ags in LCs
      but no other langerin+ DCs. Therefore, this system allows for LC-restricted Ag
      presentation to T cells. Presentation of nonsecreted OVA (GFPOVA) by steady-state
      LCs resulted in transient activation of endogenous CTL in transgenic mice.
      However, when these mice were challenged with OVA by gene gun immunization in the
      contraction phase of the primary CTL response they did not respond with a recall
      of CTL memory but, instead, with robust Ag-specific CTL tolerance. We found
      regulatory T cells (Tregs) enriched in the skin of tolerized mice, and depletion
      of Tregs or adoptive experiments revealed that Tregs were critically involved in
      CTL tolerance. By contrast, when OVA was presented by activated LCs, a recallable
      CTL memory response developed in transgenic mice. Thus, neoantigen presentation
      by epidermal LCs results in either robust CTL tolerance or CTL memory, and this
      decision-making depends on the activation state of the presenting LCs.

PMID- 28739884
TI  - Correction to: Ischemic Stroke in Nonvalvular Atrial Fibrillation at Warfarin
      Initiation: Assessment via a Large Insurance Database.

PMID- 28739882
TI  - Zebrafish B Cell Development without a Pre-B Cell Stage, Revealed by CD79
      Fluorescence Reporter Transgenes.
AB  - CD79a and CD79b proteins associate with Ig receptors as integral signaling
      components of the B cell Ag receptor complex. To study B cell development in
      zebrafish, we isolated orthologs of these genes and performed in situ
      hybridization, finding that their expression colocalized with IgH-MU in the
      kidney, which is the site of B cell development. CD79 transgenic lines were made
      by linking the promoter and upstream regulatory segments of CD79a and CD79b to
      enhanced GFP to identify B cells, as demonstrated by PCR analysis of IgH-MU
      expression in sorted cells. We crossed these CD79-GFP lines to a recombination
      activating gene (Rag)2:mCherry transgenic line to identify B cell development
      stages in kidney marrow. Initiation of CD79:GFP expression in Rag2:mCherry+ cells
      and the timing of Ig H and L chain expression revealed simultaneous expression of
      both IgH-MU- and IgL-kappa-chains, without progressing through the stage of IgH
      MU-chain alone. Rag2:mCherry+ cells without CD79:GFP showed the highest Rag1 and
      Rag2 mRNAs compared with CD79a and CD79b:GFP+ B cells, which showed strongly
      reduced Rag mRNAs. Thus, B cell development in zebrafish does not go through a
      Raghi CD79+IgH-MU+ pre-B cell stage, different from mammals. After the generation
      of CD79:GFP+ B cells, decreased CD79 expression occurred upon differentiation to
      Ig secretion, as detected by alteration from membrane to secreted IgH-MU exon
      usage, similar to in mammals. This confirmed a conserved role for CD79 in B cell
      development and differentiation, without the requirement of a pre-B cell stage in
      zebrafish.

PMID- 28739885
TI  - Correction to: THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) Mutation
      in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage.

PMID- 28739886
TI  - Correction to: Hyperlipidemia and Reduced White Matter Hyperintensity Volume in
      Patients With Ischemic Stroke.

PMID- 28739887
TI  - Correction to: Enhanced Effective Connectivity Between Primary Motor Cortex and
      Intraparietal Sulcus in Well-Recovered Stroke Patients.

PMID- 28739888
TI  - PIF3 is a negative regulator of the CBF pathway and freezing tolerance in
      Arabidopsis.
AB  - Light and temperature are major environmental factors that coordinately control
      plant growth and survival. However, how plants integrate light and temperature
      signals to better adapt to environmental stresses is poorly understood.
      PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), a key transcription factor repressing
      photomorphogenesis, has been shown to play a pivotal role in mediating plants'
      responses to various environmental signals. In this study, we found that PIF3
      functions as a negative regulator of Arabidopsis freezing tolerance by directly
      binding to the promoters of C-REPEAT BINDING FACTOR (CBF) genes to down-regulate
      their expression. In addition, two F-box proteins, EIN3-BINDING F-BOX 1 (EBF1)
      and EBF2, directly target PIF3 for 26S proteasome-mediated degradation.
      Consistently, ebf1 and ebf2 mutants were more sensitive to freezing than were the
      wild type, and the pif3 mutation suppressed the freezing-sensitive phenotype of
      ebf1 Furthermore, cold treatment promoted the degradation of EBF1 and EBF2,
      leading to increased stability of the PIF3 protein and reduced expression of the
      CBF genes. Together, our study uncovers an important role of PIF3 in Arabidopsis
      freezing tolerance by negatively regulating the expression of genes in the CBF
      pathway.

PMID- 28739889
TI  - Buying time promotes happiness.
AB  - Around the world, increases in wealth have produced an unintended consequence: a
      rising sense of time scarcity. We provide evidence that using money to buy time
      can provide a buffer against this time famine, thereby promoting happiness. Using
      large, diverse samples from the United States, Canada, Denmark, and The
      Netherlands (n = 6,271), we show that individuals who spend money on time-saving
      services report greater life satisfaction. A field experiment provides causal
      evidence that working adults report greater happiness after spending money on a
      time-saving purchase than on a material purchase. Together, these results suggest
      that using money to buy time can protect people from the detrimental effects of
      time pressure on life satisfaction.

PMID- 28739890
TI  - Two functionally distinct E2/E3 pairs coordinate sequential ubiquitination of a
      common substrate in Caenorhabditis elegans development.
AB  - Ubiquitination, the crucial posttranslational modification that regulates the
      eukaryotic proteome, is carried out by a trio of enzymes, known as E1 [ubiquitin
      (Ub)-activating enzyme], E2 (Ub-conjugating enzyme), and E3 (Ub ligase). Although
      most E2s can work with any of the three mechanistically distinct classes of E3s,
      the E2 UBCH7 is unable to function with really interesting new gene (RING)-type
      E3s, thereby restricting it to homologous to E6AP C-terminus (HECT) and RING-in
      between-RING (RBR) E3s. The Caenorhabditis elegans UBCH7 homolog, UBC-18, plays a
      critical role in developmental processes through its cooperation with the RBR E3
      ARI-1 (HHARI in humans). We discovered that another E2, ubc-3, interacts
      genetically with ubc-18 in an unbiased genome-wide RNAi screen in C. elegans
      These two E2s have nonoverlapping biochemical activities, and each is dedicated
      to distinct classes of E3s. UBC-3 is the ortholog of CDC34 that functions
      specifically with Cullin-RING E3 ligases, such as SCF (Skp1-Cullin-F-box). Our
      genetic and biochemical studies show that UBCH7 (UBC-18) and the RBR E3 HHARI
      (ARI-1) coordinate with CDC34 (UBC-3) and an SCF E3 complex to ubiquitinate a
      common substrate, a SKP1-related protein. We show that UBCH7/HHARI primes the
      substrate with a single Ub in the presence of CUL-1, and that CDC34 is required
      to build chains onto the Ub-primed substrate. Our study reveals that the
      association and coordination of two distinct E2/E3 pairs play essential roles in
      a developmental pathway and suggests that cooperative action among E3s is a
      conserved feature from worms to humans.

PMID- 28739891
TI  - BACE inhibition-dependent repair of Alzheimer's pathophysiology.
AB  - Amyloid-beta (Abeta) is thought to play an essential pathogenic role in
      Alzheimer's disease (AD). A key enzyme involved in the generation of Abeta is the
      beta-secretase BACE, for which powerful inhibitors have been developed and are
      currently in use in human clinical trials. However, although BACE inhibition can
      reduce cerebral Abeta levels, whether it also can ameliorate neural circuit and
      memory impairments remains unclear. Using histochemistry, in vivo Ca2+ imaging,
      and behavioral analyses in a mouse model of AD, we demonstrate that along with
      reducing prefibrillary Abeta surrounding plaques, the inhibition of BACE activity
      can rescue neuronal hyperactivity, impaired long-range circuit function, and
      memory defects. The functional neuronal impairments reappeared after infusion of
      soluble Abeta, mechanistically linking Abeta pathology to neuronal and cognitive
      dysfunction. These data highlight the potential benefits of BACE inhibition for
      the effective treatment of a wide range of AD-like pathophysiological and
      cognitive impairments.

PMID- 28739892
TI  - Evolutionary neuroscience of cumulative culture.
AB  - Culture suffuses all aspects of human life. It shapes our minds and bodies and
      has provided a cumulative inheritance of knowledge, skills, institutions, and
      artifacts that allows us to truly stand on the shoulders of giants. No other
      species approaches the extent, diversity, and complexity of human culture, but we
      remain unsure how this came to be. The very uniqueness of human culture is both a
      puzzle and a problem. It is puzzling as to why more species have not adopted this
      manifestly beneficial strategy and problematic because the comparative methods of
      evolutionary biology are ill suited to explain unique events. Here, we develop a
      more particularistic and mechanistic evolutionary neuroscience approach to
      cumulative culture, taking into account experimental, developmental, comparative,
      and archaeological evidence. This approach reconciles currently competing
      accounts of the origins of human culture and develops the concept of a uniquely
      human technological niche rooted in a shared primate heritage of visuomotor
      coordination and dexterous manipulation.

PMID- 28739893
TI  - Effective intermediate-spin iron in O2-transporting heme proteins.
AB  - Proteins carrying an iron-porphyrin (heme) cofactor are essential for biological
      O2 management. The nature of Fe-O2 bonding in hemoproteins is debated for
      decades. We used energy-sampling and rapid-scan X-ray Kbeta emission and K-edge
      absorption spectroscopy as well as quantum chemistry to determine molecular and
      electronic structures of unligated (deoxy), CO-inhibited (carboxy), and O2-bound
      (oxy) hemes in myoglobin (MB) and hemoglobin (HB) solutions and in porphyrin
      compounds at 20-260 K. Similar metrical and spectral features revealed analogous
      heme sites in MB and HB and the absence of low-spin (LS) to high-spin (HS)
      conversion. Amplitudes of Kbeta main-line emission spectra were directly related
      to the formal unpaired Fe(d) spin count, indicating HS Fe(II) in deoxy and LS
      Fe(II) in carboxy. For oxy, two unpaired Fe(d) spins and, thus by definition, an
      intermediate-spin iron center, were revealed by our static and kinetic X-ray
      data, as supported by (time-dependent) density functional theory and complete
      active-space self-consistent-field calculations. The emerging Fe-O2 bonding
      situation includes in essence a ferrous iron center, minor superoxide character
      of the noninnocent ligand, significant double-bond properties of the interaction,
      and three-center electron delocalization as in ozone. It resolves the apparently
      contradictory classical models of Pauling, Weiss, and McClure/Goddard into a
      unifying view of O2 bonding, tuned toward reversible oxygen transport.

PMID- 28739894
TI  - Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer
      and promiscuous spread of antibiotic resistance.
AB  - Relaxases are metal-dependent nucleases that break and join DNA for the
      initiation and completion of conjugative bacterial gene transfer. Conjugation is
      the main process through which antibiotic resistance spreads among bacteria, with
      multidrug-resistant staphylococci and streptococci infections posing major
      threats to human health. The MOBV family of relaxases accounts for approximately
      85% of all relaxases found in Staphylococcus aureus isolates. Here, we present
      six structures of the MOBV relaxase MobM from the promiscuous plasmid pMV158 in
      complex with several origin of transfer DNA fragments. A combined structural,
      biochemical, and computational approach reveals that MobM follows a previously
      uncharacterized histidine/metal-dependent DNA processing mechanism, which
      involves the formation of a covalent phosphoramidate histidine-DNA adduct for
      cell-to-cell transfer. We discuss how the chemical features of the high-energy
      phosphorus-nitrogen bond shape the dominant position of MOBV histidine relaxases
      among small promiscuous plasmids and their preference toward Gram-positive
      bacteria.

PMID- 28739895
TI  - Stem parasitic plant Cuscuta australis (dodder) transfers herbivory-induced
      signals among plants.
AB  - Cuscuta spp. (i.e., dodders) are stem parasites that naturally graft to their
      host plants to extract water and nutrients; multiple adjacent hosts are often
      parasitized by one or more Cuscuta plants simultaneously, forming connected plant
      clusters. Metabolites, proteins, and mRNAs are known to be transferred from hosts
      to Cuscuta, and Cuscuta bridges even facilitate host-to-host virus movement.
      Whether Cuscuta bridges transmit ecologically meaningful signals remains unknown.
      Here we show that, when host plants are connected by Cuscuta bridges, systemic
      herbivory signals are transmitted from attacked plants to unattacked plants, as
      revealed by the large transcriptomic changes in the attacked local leaves,
      undamaged systemic leaves of the attacked plants, and leaves of unattacked but
      connected hosts. The interplant signaling is largely dependent on the jasmonic
      acid pathway of the damaged local plants, and can be found among conspecific or
      heterospecific hosts of different families. Importantly, herbivore attack of one
      host plant elevates defensive metabolites in the other systemic Cuscuta bridge
      connected hosts, resulting in enhanced resistance against insects even in several
      consecutively Cuscuta-connected host plants over long distances (> 100 cm). By
      facilitating plant-to-plant signaling, Cuscuta provides an information-based
      means of countering the resource-based fitness costs to their hosts.

PMID- 28739896
TI  - Mitogenic stimulation accelerates influenza-induced mortality by increasing
      susceptibility of alveolar type II cells to infection.
AB  - Development of pneumonia is the most lethal consequence of influenza, increasing
      mortality more than 50-fold compared with uncomplicated infection. The spread of
      viral infection from conducting airways to the alveolar epithelium is therefore a
      pivotal event in influenza pathogenesis. We found that mitogenic stimulation with
      keratinocyte growth factor (KGF) markedly accelerated mortality after infectious
      challenge with influenza A virus (IAV). Coadministration of KGF with IAV markedly
      accelerated the spread of viral infection from the airways to alveoli compared
      with challenge with IAV alone, based on spatial and temporal analyses of viral
      nucleoprotein staining of lung tissue sections and dissociated lung cells. To
      better define the temporal relationship between KGF administration and
      susceptibility to IAV infection in vivo, we administered KGF 120, 48, 24, and 0 h
      before intrapulmonary IAV challenge and assessed the percentages of proliferating
      and IAV-infected, alveolar type II (AECII) cells in dispersed lung cell
      populations. Peak AECII infectivity coincided with the timing of KGF
      administration that also induced peak AECII proliferation. AECII from mice that
      were given intrapulmonary KGF before isolation and then infected with IAV ex vivo
      exhibited the same temporal pattern of proliferation and infectious
      susceptibility. KGF-induced increases in mortality, AECII proliferation, and
      enhanced IAV susceptibility were all reversed by pretreatment of the animals with
      the mTOR inhibitor rapamycin before mitogenic stimulation. Taken together, these
      data suggest mTOR signaling-dependent, mitogenic conditioning of AECII is a
      determinant of host susceptibility to infection with IAV.

PMID- 28739897
TI  - Antibacterial photosensitization through activation of coproporphyrinogen
      oxidase.
AB  - Gram-positive bacteria cause the majority of skin and soft tissue infections
      (SSTIs), resulting in the most common reason for clinic visits in the United
      States. Recently, it was discovered that Gram-positive pathogens use a unique
      heme biosynthesis pathway, which implicates this pathway as a target for
      development of antibacterial therapies. We report here the identification of a
      small-molecule activator of coproporphyrinogen oxidase (CgoX) from Gram-positive
      bacteria, an enzyme essential for heme biosynthesis. Activation of CgoX induces
      accumulation of coproporphyrin III and leads to photosensitization of Gram
      positive pathogens. In combination with light, CgoX activation reduces bacterial
      burden in murine models of SSTI. Thus, small-molecule activation of CgoX
      represents an effective strategy for the development of light-based antimicrobial
      therapies.

PMID- 28739898
TI  - Mapping of human brown adipose tissue in lean and obese young men.
AB  - Human brown adipose tissue (BAT) can be activated to increase glucose uptake and
      energy expenditure, making it a potential target for treating obesity and
      metabolic disease. Data on the functional and anatomic characteristics of BAT are
      limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI)
      23.2 +/- 1.9 kg/m2; 8 obese, BMI 34.8 +/- 3.3 kg/m2] after 5 h of tolerable cold
      exposure, we measured BAT volume and activity by 18F-labeled fluorodeoxyglucose
      positron emission tomography/computerized tomography (PET/CT). Obese men had less
      activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing
      depots (mean, 1,646 vs. 855 mL) with a wide range (0.1-71%) in the ratio of
      activated BAT to inactive fat between individuals. Six anatomic regions had
      activated BAT-cervical, supraclavicular, axillary, mediastinal, paraspinal, and
      abdominal-with 67 +/- 20% of all activated BAT concentrated in a continuous
      fascial layer comprising the first three depots in the upper torso. These
      nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat
      mass), and up to 90% of each depot could be activated BAT. The amount and
      activity of BAT was significantly influenced by region of interest selection
      methods, PET threshold criteria, and PET resolutions. The present study suggests
      that active BAT can be found in specific adipose depots in adult humans, but less
      than one-half of the fat in these depots is stimulated by acute cold exposure,
      demonstrating a previously underappreciated thermogenic potential.

PMID- 28739899
TI  - Activin signaling mediates muscle-to-adipose communication in a mitochondria
      dysfunction-associated obesity model.
AB  - Mitochondrial dysfunction has been associated with obesity and metabolic
      disorders. However, whether mitochondrial perturbation in a single tissue
      influences mitochondrial function and metabolic status of another distal tissue
      remains largely unknown. We analyzed the nonautonomous role of muscular
      mitochondrial dysfunction in Drosophila Surprisingly, impaired muscle
      mitochondrial function via complex I perturbation results in simultaneous
      mitochondrial dysfunction in the fat body (the fly adipose tissue) and subsequent
      triglyceride accumulation, the major characteristic of obesity. RNA-sequencing
      (RNA-seq) analysis, in the context of muscle mitochondrial dysfunction, revealed
      that target genes of the TGF-beta signaling pathway were induced in the fat body.
      Strikingly, expression of the TGF-beta family ligand, Activin-beta (Actbeta), was
      dramatically increased in the muscles by NF-kappaB/Relish (Rel) signaling in
      response to mitochondrial perturbation, and decreasing Actbeta expression in
      mitochondrial-perturbed muscles rescued both the fat body mitochondrial
      dysfunction and obesity phenotypes. Thus, perturbation of muscle mitochondrial
      activity regulates mitochondrial function in the fat body nonautonomously via
      modulation of Activin signaling.

PMID- 28739900
TI  - Changes in human skull morphology across the agricultural transition are
      consistent with softer diets in preindustrial farming groups.
AB  - Agricultural foods and technologies are thought to have eased the mechanical
      demands of diet-how often or how hard one had to chew-in human populations
      worldwide. Some evidence suggests correspondingly worldwide changes in skull
      shape and form across the agricultural transition, although these changes have
      proved difficult to characterize at a global scale. Here, adapting a quantitative
      genetics mixed model for complex phenotypes, we quantify the influence of diet on
      global human skull shape and form. We detect modest directional differences
      between foragers and farmers. The effects are consistent with softer diets in
      preindustrial farming groups and are most pronounced and reliably directional
      when the farming class is limited to dairying populations. Diet effect magnitudes
      are relatively small, affirming the primary role of neutral evolutionary
      processes-genetic drift, mutation, and gene flow structured by population history
      and migrations-in shaping diversity in the human skull. The results also bring an
      additional perspective to the paradox of why Homo sapiens, particularly
      agriculturalists, appear to be relatively well suited to efficient (high
      leverage) chewing.

PMID- 28739901
TI  - Profile of Christine Petit.

PMID- 28739902
TI  - Rho-associated kinase is a therapeutic target in neuroblastoma.
AB  - Neuroblastoma is a peripheral neural system tumor that originates from the neural
      crest and is the most common and deadly tumor of infancy. Here we show that
      neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho
      signaling cascade important for proper migration and differentiation of neural
      crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma
      patients, and elevated expression of Rho-associated kinase (ROCK)2 is associated
      with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2,
      key molecules in Rho signaling, resulted in neuroblastoma cell differentiation
      and inhibition of neuroblastoma cell growth, migration, and invasion.
      Molecularly, ROCK inhibition induced glycogen synthase kinase 3beta-dependent
      phosphorylation and degradation of MYCN protein. Small-molecule inhibition of
      ROCK suppressed MYCN-driven neuroblastoma growth in TH-MYCN homozygous transgenic
      mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice.
      Interference with Rho/Rac signaling might offer therapeutic perspectives for high
      risk neuroblastoma.

PMID- 28739903
TI  - Interdomain conformational flexibility underpins the activity of UGGT, the
      eukaryotic glycoprotein secretion checkpoint.
AB  - Glycoproteins traversing the eukaryotic secretory pathway begin life in the
      endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP
      glucose:glycoprotein glucosyltransferase (UGGT). The enzyme acts as the single
      glycoprotein folding quality control checkpoint: it selectively reglucosylates
      misfolded glycoproteins, promotes their association with ER lectins and
      associated chaperones, and prevents premature secretion from the ER. UGGT has
      long resisted structural determination and sequence-based domain boundary
      prediction. Questions remain on how this single enzyme can flag misfolded
      glycoproteins of different sizes and shapes for ER retention and how it can span
      variable distances between the site of misfold and a glucose-accepting N-linked
      glycan on the same glycoprotein. Here, crystal structures of a full-length
      eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long
      arc that terminates in two beta-sandwiches tightly clasping the
      glucosyltransferase domain. The fold of the molecule is topologically complex,
      with the first beta-sandwich and the fourth TRXL domain being encoded by
      nonconsecutive stretches of sequence. In addition to the crystal structures, a 15
      A cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains.
      Double cysteine point mutants that engineer extra interdomain disulfide bridges
      rigidify the UGGT structure and exhibit impaired activity. The intrinsic
      flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the
      promiscuity needed to recognize and reglucosylate its many different substrates
      and/or enable reglucosylation of N-linked glycans situated at variable distances
      from the site of misfold.

PMID- 28739904
TI  - Exposure to and recall of violence reduce short-term memory and cognitive
      control.
AB  - Previous research has investigated the effects of violence and warfare on
      individuals' well-being, mental health, and individual prosociality and risk
      aversion. This study establishes the short- and long-term effects of exposure to
      violence on short-term memory and aspects of cognitive control. Short-term memory
      is the ability to store information. Cognitive control is the capacity to exert
      inhibition, working memory, and cognitive flexibility. Both have been shown to
      affect positively individual well-being and societal development. We sampled
      Colombian civilians who were exposed either to urban violence or to warfare more
      than a decade earlier. We assessed exposure to violence through either the urban
      district-level homicide rate or self-reported measures. Before undertaking
      cognitive tests, a randomly selected subset of our sample was asked to recall
      emotions of anxiety and fear connected to experiences of violence, whereas the
      rest recalled joyful or emotionally neutral experiences. We found that higher
      exposure to violence was associated with lower short-term memory abilities and
      lower cognitive control in the group recalling experiences of violence, whereas
      it had no effect in the other group. This finding demonstrates that exposure to
      violence, even if a decade earlier, can hamper cognitive functions, but only
      among individuals actively recalling emotional states linked with such
      experiences. A laboratory experiment conducted in Germany aimed to separate the
      effect of recalling violent events from the effect of emotions of fear and
      anxiety. Both factors had significant negative effects on cognitive functions and
      appeared to be independent from each other.

PMID- 28739905
TI  - Effect of ATP and regulatory light-chain phosphorylation on the polymerization of
      mammalian nonmuscle myosin II.
AB  - Addition of 1 mM ATP substantially reduces the light scattering of solutions of
      polymerized unphosphorylated nonmuscle myosin IIs (NM2s), and this is reversed by
      phosphorylation of the regulatory light chain (RLC). It has been proposed that
      these changes result from substantial depolymerization of unphosphorylated NM2
      filaments to monomers upon addition of ATP, and filament repolymerization upon
      RLC-phosphorylation. We now show that the differences in myosin monomer
      concentration of RLC-unphosphorylated and -phosphorylated recombinant mammalian
      NM2A, NM2B, and NM2C polymerized in the presence of ATP are much too small to
      explain their substantial differences in light scattering. Rather, we find that
      the decrease in light scattering upon addition of ATP to polymerized
      unphosphorylated NM2s correlates with the formation of dimers, tetramers, and
      hexamers, in addition to monomers, an increase in length, and decrease in width
      of the bare zones of RLC-unphosphorylated filaments. Both effects of ATP addition
      are reversed by phosphorylation of the RLC. Our data also suggest that, contrary
      to previous models, assembly of RLC-phosphorylated NM2s at physiological ionic
      strength proceeds from folded monomers to folded antiparallel dimers, tetramers,
      and hexamers that unfold and polymerize into antiparallel filaments. This model
      could explain the dynamic relocalization of NM2 filaments in vivo by
      dephosphorylation of RLC-phosphorylated filaments, disassembly of the
      dephosphorylated filaments to folded monomers, dimers, and small oligomers,
      followed by diffusion of these species, and reassembly of filaments at the new
      location following rephosphorylation of the RLC.

PMID- 28739906
TI  - Social network fragmentation and community health.
AB  - Community health interventions often seek to intentionally destroy paths between
      individuals to prevent the spread of infectious diseases. Immunizing individuals
      through direct vaccination or the provision of health education prevents pathogen
      transmission and the propagation of misinformation concerning medical treatments.
      However, it remains an open question whether network-based strategies should be
      used in place of conventional field approaches to target individuals for medical
      treatment in low-income countries. We collected complete friendship and health
      advice networks in 17 rural villages of Mayuge District, Uganda. Here we show
      that acquaintance algorithms, i.e., selecting neighbors of randomly selected
      nodes, were systematically more efficient in fragmenting all networks than
      targeting well-established community roles, i.e., health workers, village
      government members, and schoolteachers. Additionally, community roles were not
      good proxy indicators of physical proximity to other households or connections to
      many sick people. We also show that acquaintance algorithms were effective in
      offsetting potential noncompliance with deworming treatments for 16,357
      individuals during mass drug administration (MDA). Health advice networks were
      destroyed more easily than friendship networks. Only an average of 32% of nodes
      were removed from health advice networks to reduce the percentage of nodes at
      risk for refusing treatment in MDA to below 25%. Treatment compliance of at least
      75% is needed in MDA to control human morbidity attributable to parasitic worms
      and progress toward elimination. Our findings point toward the potential use of
      network-based approaches as an alternative to role-based strategies for targeting
      individuals in rural health interventions.

PMID- 28739907
TI  - A promiscuous split intein with expanded protein engineering applications.
AB  - The protein trans-splicing (PTS) activity of naturally split inteins has found
      widespread use in chemical biology and biotechnology. However, currently used
      naturally split inteins suffer from an "extein dependence," whereby residues
      surrounding the splice junction strongly affect splicing efficiency, limiting the
      general applicability of many PTS-based methods. To address this, we describe a
      mechanism-guided protein engineering approach that imbues ultrafast DnaE split
      inteins with minimal extein dependence. The resulting "promiscuous" inteins are
      shown to be superior reagents for protein cyclization and protein semisynthesis,
      with the latter illustrated through the modification of native cellular
      chromatin. The promiscuous inteins reported here thus improve the applicability
      of existing PTS methods and should enable future efforts to engineer promiscuity
      into other naturally split inteins.

PMID- 28739908
TI  - Molecular mechanism of photoactivation of a light-regulated adenylate cyclase.
AB  - The photoactivated adenylate cyclase (PAC) from the photosynthetic cyanobacterium
      Oscillatoria acuminata (OaPAC) detects light through a flavin chromophore within
      the N-terminal BLUF domain. BLUF domains have been found in a number of different
      light-activated proteins, but with different relative orientations. The two BLUF
      domains of OaPAC are found in close contact with each other, forming a coiled
      coil at their interface. Crystallization does not impede the activity switching
      of the enzyme, but flash cooling the crystals to cryogenic temperatures prevents
      the signature spectral changes that occur on photoactivation/deactivation. High
      resolution crystallographic analysis of OaPAC in the fully activated state has
      been achieved by cryocooling the crystals immediately after light exposure.
      Comparison of the isomorphous light- and dark-state structures shows that the
      active site undergoes minimal changes, yet enzyme activity may increase up to 50
      fold, depending on conditions. The OaPAC models will assist the development of
      simple, direct means to raise the cyclic AMP levels of living cells by light, and
      other tools for optogenetics.

PMID- 28739909
TI  - Solution structure of the TLR adaptor MAL/TIRAP reveals an intact BB loop and
      supports MAL Cys91 glutathionylation for signaling.
AB  - MyD88 adaptor-like (MAL) is a critical protein in innate immunity, involved in
      signaling by several Toll-like receptors (TLRs), key pattern recognition
      receptors (PRRs). Crystal structures of MAL revealed a nontypical
      Toll/interleukin-1 receptor (TIR)-domain fold stabilized by two disulfide
      bridges. We therefore undertook a structural and functional analysis of the role
      of reactive cysteine residues in the protein. Under reducing conditions, the
      cysteines do not form disulfides, but under oxidizing conditions they are highly
      amenable to modification. The solution structure of the reduced form of the MAL
      TIR domain, determined by NMR spectroscopy, reveals a remarkable structural
      rearrangement compared with the disulfide-bonded structure, which includes the
      relocation of a beta-strand and repositioning of the functionally important "BB
      loop" region to a location more typical for TIR domains. Redox measurements by
      NMR further reveal that C91 has the highest redox potential of all cysteines in
      MAL. Indeed, mass spectrometry revealed that C91 undergoes glutathionylation in
      macrophages activated with the TLR4 ligand lipopolysaccharide (LPS). The C91A
      mutation limits MAL glutathionylation and acts as a dominant negative, blocking
      the interaction of MAL with its downstream target MyD88. The H92P mutation mimics
      the dominant-negative effects of the C91A mutation, presumably by preventing C91
      glutathionylation. The MAL C91A and H92P mutants also display diminished
      degradation and interaction with interleukin-1 receptor-associated kinase 4
      (IRAK4). We conclude that in the cell, MAL is not disulfide-bonded and requires
      glutathionylation of C91 for signaling.

PMID- 28739910
TI  - Identifying early modern human ecological niche expansions and associated
      cultural dynamics in the South African Middle Stone Age.
AB  - The archaeological record shows that typically human cultural traits emerged at
      different times, in different parts of the world, and among different hominin
      taxa. This pattern suggests that their emergence is the outcome of complex and
      nonlinear evolutionary trajectories, influenced by environmental, demographic,
      and social factors, that need to be understood and traced at regional scales. The
      application of predictive algorithms using archaeological and paleoenvironmental
      data allows one to estimate the ecological niches occupied by past human
      populations and identify niche changes through time, thus providing the
      possibility of investigating relationships between cultural innovations and
      possible niche shifts. By using such methods to examine two key southern Africa
      archaeological cultures, the Still Bay [76-71 thousand years before present (ka)]
      and the Howiesons Poort (HP; 66-59 ka), we identify a niche shift characterized
      by a significant expansion in the breadth of the HP ecological niche. This
      expansion is coincident with aridification occurring across Marine Isotope Stage
      4 (ca. 72-60 ka) and especially pronounced at 60 ka. We argue that this niche
      shift was made possible by the development of a flexible technological system,
      reliant on composite tools and cultural transmission strategies based more on
      "product copying" rather than "process copying." These results counter the one
      niche/one human taxon equation. They indicate that what makes our cultures, and
      probably the cultures of other members of our lineage, unique is their
      flexibility and ability to produce innovations that allow a population to shift
      its ecological niche.

PMID- 28739911
TI  - Deacetylase activity of histone deacetylase 3 is required for productive VDJ
      recombination and B-cell development.
AB  - Histone deacetylase 3 (HDAC3) is the catalytic component of NCoR/SMRT corepressor
      complexes that mediate the actions of transcription factors implicated in the
      regulation of B-cell development and function. We crossed Hdac3 conditional
      knockout mice with Mb1-Cre knockin animals to delete Hdac3 in early progenitor B
      cells. The spleens of Hdac3F/-Mb1-Cre+/- mice were virtually devoid of mature B
      cells, and B220+CD43+ B-cell progenitors accumulated within the bone marrow.
      Quantitative deep sequencing of the Ig heavy chain locus from B220+CD43+
      populations identified a defect in VHDJH recombination with a severe reduction in
      productive rearrangements, which directly corresponded to the loss of pre-B cells
      from Hdac3Delta/- bone marrow. For Hdac3Delta/- B cells that did show productive
      VDJ rearrangement, there was significant skewing toward the incorporation of
      proximal VH gene segments and a corresponding reduction in distal VH gene segment
      use. Although transcriptional effects within these loci were modest, Hdac3Delta/-
      progenitor cells displayed global changes in chromatin structure that likely
      hindered effective distal V-DJ recombination. Reintroduction of wild-type Hdac3
      restored normal B-cell development, whereas an Hdac3 point mutant lacking
      deacetylase activity failed to complement this defect. Thus, the deacetylase
      activity of Hdac3 is required for the generation of mature B cells.

PMID- 28739912
TI  - The critical phase for visual control of human walking over complex terrain.
AB  - To walk efficiently over complex terrain, humans must use vision to tailor their
      gait to the upcoming ground surface without interfering with the exploitation of
      passive mechanical forces. We propose that walkers use visual information to
      initialize the mechanical state of the body before the beginning of each step so
      the resulting ballistic trajectory of the walker's center-of-mass will facilitate
      stepping on target footholds. Using a precision stepping task and synchronizing
      target visibility to the gait cycle, we empirically validated two predictions
      derived from this strategy: (1) Walkers must have information about upcoming
      footholds during the second half of the preceding step, and (2) foot placement is
      guided by information about the position of the target foothold relative to the
      preceding base of support. We conclude that active and passive modes of control
      work synergistically to allow walkers to negotiate complex terrain with
      efficiency, stability, and precision.

PMID- 28739913
TI  - Rainforest metropolis casts 1,000-km defaunation shadow.
AB  - Tropical rainforest regions are urbanizing rapidly, yet the role of emerging
      metropolises in driving wildlife overharvesting in forests and inland waters is
      unknown. We present evidence of a large defaunation shadow around a rainforest
      metropolis. Using interviews with 392 rural fishers, we show that fishing has
      severely depleted a large-bodied keystone fish species, tambaqui (Colossoma
      macropomum), with an impact extending over 1,000 km from the rainforest city of
      Manaus (population 2.1 million). There was strong evidence of defaunation within
      this area, including a 50% reduction in body size and catch rate (catch per unit
      effort). Our findings link these declines to city-based boats that provide rural
      fishers with reliable access to fish buyers and ice and likely impact rural
      fisher livelihoods and flooded forest biodiversity. This empirical evidence that
      urban markets can defaunate deep into rainforest wilderness has implications for
      other urbanizing socioecological systems.

PMID- 28739914
TI  - HEMO, an ancestral endogenous retroviral envelope protein shed in the blood of
      pregnant women and expressed in pluripotent stem cells and tumors.
AB  - Capture of retroviral envelope genes is likely to have played a role in the
      emergence of placental mammals, with evidence for multiple, reiterated, and
      independent capture events occurring in mammals, and be responsible for the
      diversity of present day placental structures. Here, we uncover a full-length
      endogenous retrovirus envelope protein, dubbed HEMO [human endogenous MER34
      (medium-reiteration-frequency-family-34) ORF], with unprecedented
      characteristics, because it is actively shed in the blood circulation in humans
      via specific cleavage of the precursor envelope protein upstream of the
      transmembrane domain. At variance with previously identified retroviral envelope
      genes, its encoding gene is found to be transcribed from a unique CpG-rich
      promoter not related to a retroviral LTR, with sites of expression including the
      placenta as well as other tissues and rather unexpectedly, stem cells as well as
      reprogrammed induced pluripotent stem cells (iPSCs), where the protein can also
      be detected. We provide evidence that the associated retroviral capture event
      most probably occurred >100 Mya before the split of Laurasiatheria and
      Euarchontoglires, with the identified retroviral envelope gene encoding a full
      length protein in all simians under purifying selection and with similar shedding
      capacity. Finally, a comprehensive screen of the expression of the gene discloses
      high transcript levels in several tumor tissues, such as germ cell, breast, and
      ovarian tumors, with in the latter case, evidence for a histotype dependence and
      specific protein expression in clear-cell carcinoma. Altogether, the identified
      protein could constitute a "stemness marker" of the normal cell and a possible
      target for immunotherapeutic approaches in tumors.

PMID- 28739915
TI  - Interactions between feedback and lateral connections in the primary visual
      cortex.
AB  - Perceptual grouping of line segments into object contours has been thought to be
      mediated, in part, by long-range horizontal connectivity intrinsic to the primary
      visual cortex (V1), with a contribution by top-down feedback projections. To
      dissect the contributions of intraareal and interareal connections during contour
      integration, we applied conditional Granger causality analysis to assess
      directional influences among neural signals simultaneously recorded from visual
      cortical areas V1 and V4 of monkeys performing a contour detection task. Our
      results showed that discounting the influences from V4 markedly reduced V1
      lateral interactions, indicating dependence on feedback signals of the effective
      connectivity within V1. On the other hand, the feedback influences were
      reciprocally dependent on V1 lateral interactions because the modulation
      strengths from V4 to V1 were greatly reduced after discounting the influences
      from other V1 neurons. Our findings suggest that feedback and lateral connections
      closely interact to mediate image grouping and segmentation.

PMID- 28739916
TI  - QnAs with Liqun Luo.

PMID- 28739917
TI  - Changes in cognitive flexibility and hypothesis search across human life history
      from childhood to adolescence to adulthood.
AB  - How was the evolution of our unique biological life history related to
      distinctive human developments in cognition and culture? We suggest that the
      extended human childhood and adolescence allows a balance between exploration and
      exploitation, between wider and narrower hypothesis search, and between
      innovation and imitation in cultural learning. In particular, different
      developmental periods may be associated with different learning strategies. This
      relation between biology and culture was probably coevolutionary and
      bidirectional: life-history changes allowed changes in learning, which in turn
      both allowed and rewarded extended life histories. In two studies, we test how
      easily people learn an unusual physical or social causal relation from a pattern
      of evidence. We track the development of this ability from early childhood
      through adolescence and adulthood. In the physical domain, preschoolers,
      counterintuitively, perform better than school-aged children, who in turn perform
      better than adolescents and adults. As they grow older learners are less
      flexible: they are less likely to adopt an initially unfamiliar hypothesis that
      is consistent with new evidence. Instead, learners prefer a familiar hypothesis
      that is less consistent with the evidence. In the social domain, both
      preschoolers and adolescents are actually the most flexible learners, adopting an
      unusual hypothesis more easily than either 6-y-olds or adults. There may be
      important developmental transitions in flexibility at the entry into middle
      childhood and in adolescence, which differ across domains.

PMID- 28739918
TI  - Medial temporal lobe and topographical memory.
AB  - There has been interest in the idea that medial temporal lobe (MTL) structures
      might be especially important for spatial processing and spatial memory. We
      tested the proposal that the MTL has a specific role in topographical memory as
      assessed in tasks of scene memory where the viewpoint shifts from study to test.
      Building on materials used previously for such studies, we administered three
      different tasks in a total of nine conditions. Participants studied a scene
      depicting four hills of different shapes and sizes and made a choice among four
      test images. In the Rotation task, the correct choice depicted the study scene
      from a shifted perspective. MTL patients succeeded when the study and test images
      were presented together but failed the moment the study scene was removed (even
      at a 0-s delay). In the No-Rotation task, the correct choice was a duplicate of
      the study scene. Patients were impaired to the same extent in the No-Rotation and
      Rotation tasks after matching for difficulty. Thus, an inability to accommodate
      changes in viewpoint does not account for patient impairment. In the Nonspatial
      Perceptual task, the correct choice depicted the same overall coloring as the
      study scene. Patients were intact at a 2-s delay but failed at longer,
      distraction-filled delays. The different results for the spatial and nonspatial
      tasks are discussed in terms of differences in demand on working memory. We
      suggest that the difficulty of the spatial tasks rests on the neocortex and on
      the limitations of working memory, not on the MTL.

PMID- 28739919
TI  - LEC1 sequentially regulates the transcription of genes involved in diverse
      developmental processes during seed development.
AB  - LEAFY COTYLEDON1 (LEC1), an atypical subunit of the nuclear transcription factor
      Y (NF-Y) CCAAT-binding transcription factor, is a central regulator that controls
      many aspects of seed development including the maturation phase during which
      seeds accumulate storage macromolecules and embryos acquire the ability to
      withstand desiccation. To define the gene networks and developmental processes
      controlled by LEC1, genes regulated directly by and downstream of LEC1 were
      identified. We compared the mRNA profiles of wild-type and lec1-null mutant seeds
      at several stages of development to define genes that are down-regulated or up
      regulated by the lec1 mutation. We used ChIP and differential gene-expression
      analyses in Arabidopsis seedlings overexpressing LEC1 and in developing
      Arabidopsis and soybean seeds to identify globally the target genes that are
      transcriptionally regulated by LEC1 in planta Collectively, our results show that
      LEC1 controls distinct gene sets at different developmental stages, including
      those that mediate the temporal transition between photosynthesis and chloroplast
      biogenesis early in seed development and seed maturation late in development.
      Analyses of enriched DNA sequence motifs that may act as cis-regulatory elements
      in the promoters of LEC1 target genes suggest that LEC1 may interact with other
      transcription factors to regulate distinct gene sets at different stages of seed
      development. Moreover, our results demonstrate strong conservation in the
      developmental processes and gene networks regulated by LEC1 in two dicotyledonous
      plants that diverged ~92 Mya.

PMID- 28739920
TI  - Optimal decision making and matching are tied through diminishing returns.
AB  - How individuals make decisions has been a matter of long-standing debate among
      economists and researchers in the life sciences. In economics, subjects are
      viewed as optimal decision makers who maximize their overall reward income. This
      framework has been widely influential, but requires a complete knowledge of the
      reward contingencies associated with a given choice situation. Psychologists and
      ecologists have observed that individuals tend to use a simpler "matching"
      strategy, distributing their behavior in proportion to relative rewards
      associated with their options. This article demonstrates that the two dominant
      frameworks of choice behavior are linked through the law of diminishing returns.
      The relatively simple matching can in fact provide maximal reward when the
      rewards associated with decision makers' options saturate with the invested
      effort. Such saturating relationships between reward and effort are hallmarks of
      the law of diminishing returns. Given the prevalence of diminishing returns in
      nature and social settings, this finding can explain why humans and animals so
      commonly behave according to the matching law. The article underscores the
      importance of the law of diminishing returns in choice behavior.

PMID- 28739921
TI  - Unique structural features of the AIPL1-FKBP domain that support prenyl lipid
      binding and underlie protein malfunction in blindness.
AB  - FKBP-domain proteins (FKBPs) are pivotal modulators of cellular signaling,
      protein folding, and gene transcription. Aryl hydrocarbon receptor-interacting
      protein-like 1 (AIPL1) is a distinctive member of the FKBP superfamily in terms
      of its biochemical properties, and it plays an important biological role as a
      chaperone of phosphodiesterase 6 (PDE6), an effector enzyme of the visual
      transduction cascade. Malfunction of mutant AIPL1 proteins triggers a severe form
      of Leber congenital amaurosis and leads to blindness. The mechanism underlying
      the chaperone activity of AIPL1 is largely unknown, but involves the binding of
      isoprenyl groups on PDE6 to the FKBP domain of AIPL1. We solved the crystal
      structures of the AIPL1-FKBP domain and its pathogenic mutant V71F, both in the
      apo form and in complex with isoprenyl moieties. These structures reveal a module
      for lipid binding that is unparalleled within the FKBP superfamily. The prenyl
      binding is enabled by a unique "loop-out" conformation of the beta4-alpha1 loop
      and a conformational "flip-out" switch of the key W72 residue. A second major
      conformation of apo AIPL1-FKBP was identified by NMR studies. This conformation,
      wherein W72 flips into the ligand-binding pocket and renders the protein
      incapable of prenyl binding, is supported by molecular dynamics simulations and
      appears to underlie the pathogenicity of the V71F mutant. Our findings offer
      critical insights into the mechanisms that underlie AIPL1 function in health and
      disease, and highlight the structural and functional diversity of the FKBPs.

PMID- 28739922
TI  - Salate derivatives found in sunscreens block experimental autoimmune
      encephalomyelitis in mice.
AB  - UV light suppresses experimental autoimmune encephalomyelitis (EAE), a widely
      used animal model of MS, in mice and may be responsible for the decreased
      incidence of MS in equatorial regions. To test this concept further, we applied
      commercially available sunblock preparations to mice before exposing them to UV
      radiation. Surprisingly, some of the sunblock preparations blocked EAE without UV
      radiation. Furthermore, various sunblock preparations had variable ability to
      suppress EAE. By examining the components of the most effective agents, we
      identified homosalate and octisalate as the components responsible for
      suppressing EAE. Thus, salates may be useful in stopping the progression of MS,
      and may provide new insight into mechanisms of controlling autoimmune disease.

PMID- 28739923
TI  - Therapeutically targeting glypican-2 via single-domain antibody-based chimeric
      antigen receptors and immunotoxins in neuroblastoma.
AB  - Neuroblastoma is a childhood cancer that is fatal in almost half of patients
      despite intense multimodality treatment. This cancer is derived from
      neuroendocrine tissue located in the sympathetic nervous system. Glypican-2
      (GPC2) is a cell surface heparan sulfate proteoglycan that is important for
      neuronal cell adhesion and neurite outgrowth. In this study, we find that GPC2
      protein is highly expressed in about half of neuroblastoma cases and that high
      GPC2 expression correlates with poor overall survival compared with patients with
      low GPC2 expression. We demonstrate that silencing of GPC2 by CRISPR-Cas9 or
      siRNA results in the inhibition of neuroblastoma tumor cell growth. GPC2
      silencing inactivates Wnt/beta-catenin signaling and reduces the expression of
      the target gene N-Myc, an oncogenic driver of neuroblastoma tumorigenesis. We
      have isolated human single-domain antibodies specific for GPC2 by phage display
      technology and found that the single-domain antibodies can inhibit active beta
      catenin signaling by disrupting the interaction of GPC2 and Wnt3a. To explore
      GPC2 as a potential target in neuroblastoma, we have developed two forms of
      antibody therapeutics, immunotoxins and chimeric antigen receptor (CAR) T cells.
      Immunotoxin treatment was demonstrated to inhibit neuroblastoma growth in mice.
      CAR T cells targeting GPC2 eliminated tumors in a disseminated neuroblastoma
      mouse model where tumor metastasis had spread to multiple clinically relevant
      sites, including spine, skull, legs, and pelvis. This study suggests GPC2 as a
      promising therapeutic target in neuroblastoma.

PMID- 28739925
TI  - Large numbers of explanatory variables, a semi-descriptive analysis.
AB  - Data with a relatively small number of study individuals and a very large number
      of potential explanatory features arise particularly, but by no means only, in
      genomics. A powerful method of analysis, the lasso [Tibshirani R (1996) J Roy
      Stat Soc B 58:267-288], takes account of an assumed sparsity of effects, that is,
      that most of the features are nugatory. Standard criteria for model fitting, such
      as the method of least squares, are modified by imposing a penalty for each
      explanatory variable used. There results a single model, leaving open the
      possibility that other sparse choices of explanatory features fit virtually
      equally well. The method suggested in this paper aims to specify simple models
      that are essentially equally effective, leaving detailed interpretation to the
      specifics of the particular study. The method hinges on the ability to make
      initially a very large number of separate analyses, allowing each explanatory
      feature to be assessed in combination with many other such features. Further
      stages allow the assessment of more complex patterns such as nonlinear and
      interactive dependences. The method has formal similarities to so-called
      partially balanced incomplete block designs introduced 80 years ago [Yates F
      (1936) J Agric Sci 26:424-455] for the study of large-scale plant breeding
      trials. The emphasis in this paper is strongly on exploratory analysis; the more
      formal statistical properties obtained under idealized assumptions will be
      reported separately.

PMID- 28739924
TI  - The extension of biology through culture.

PMID- 28739926
TI  - Correction for Wu et al., Multiensemble Markov models of molecular thermodynamics
      and kinetics.

PMID- 28739927
TI  - Culture extends the scope of evolutionary biology in the great apes.
AB  - Discoveries about the cultures and cultural capacities of the great apes have
      played a leading role in the recognition emerging in recent decades that cultural
      inheritance can be a significant factor in the lives not only of humans but also
      of nonhuman animals. This prominence derives in part from these primates being
      those with whom we share the most recent common ancestry, thus offering clues to
      the origins of our own thoroughgoing reliance on cumulative cultural
      achievements. In addition, the intense research focus on these species has
      spawned an unprecedented diversity of complementary methodological approaches,
      the results of which suggest that cultural phenomena pervade the lives of these
      apes, with potentially major implications for their broader evolutionary biology.
      Here I review what this extremely broad array of observational and experimental
      methodologies has taught us about the cultural lives of chimpanzees, gorillas,
      and orangutans and consider the ways in which this knowledge extends our wider
      understanding of primate biology and the processes of adaptation and evolution
      that shape it. I address these issues first by evaluating the extent to which the
      results of cultural inheritance echo a suite of core principles that underlie
      organic Darwinian evolution but also extend them in new ways and then by
      assessing the principal causal interactions between the primary, genetically
      based organic processes of evolution and the secondary system of cultural
      inheritance that is based on social learning from others.

PMID- 28739928
TI  - Assessing benefits, costs, and disparate racial impacts of confrontational
      proactive policing.
AB  - Effective policing in a democratic society must balance the sometime conflicting
      objectives of public safety and community trust. This paper uses a formal model
      of optimal policing to explore how society might reasonably resolve the tension
      between these two objectives as well as evaluate disparate racial impacts. We do
      so by considering the social benefits and costs of confrontational types of
      proactive policing, such as stop, question, and frisk. Three features of the
      optimum that are particularly relevant to policy choices are explored: (i) the
      cost of enforcement against the innocent, (ii) the baseline level of crime rate
      without confrontational enforcement, and (iii) differences across demographic
      groups in the optimal rate of enforcement.

PMID- 28739929
TI  - Pursuing Darwin's curious parallel: Prospects for a science of cultural
      evolution.
AB  - In the past few decades, scholars from several disciplines have pursued the
      curious parallel noted by Darwin between the genetic evolution of species and the
      cultural evolution of beliefs, skills, knowledge, languages, institutions, and
      other forms of socially transmitted information. Here, I review current progress
      in the pursuit of an evolutionary science of culture that is grounded in both
      biological and evolutionary theory, but also treats culture as more than a
      proximate mechanism that is directly controlled by genes. Both genetic and
      cultural evolution can be described as systems of inherited variation that change
      over time in response to processes such as selection, migration, and drift.
      Appropriate differences between genetic and cultural change are taken seriously,
      such as the possibility in the latter of nonrandomly guided variation or
      transformation, blending inheritance, and one-to-many transmission. The
      foundation of cultural evolution was laid in the late 20th century with
      population-genetic style models of cultural microevolution, and the use of
      phylogenetic methods to reconstruct cultural macroevolution. Since then, there
      have been major efforts to understand the sociocognitive mechanisms underlying
      cumulative cultural evolution, the consequences of demography on cultural
      evolution, the empirical validity of assumed social learning biases, the relative
      role of transformative and selective processes, and the use of quantitative
      phylogenetic and multilevel selection models to understand past and present
      dynamics of society-level change. I conclude by highlighting the
      interdisciplinary challenges of studying cultural evolution, including its
      relation to the traditional social sciences and humanities.

PMID- 28739930
TI  - Nuclear carbonic anhydrase 6B associates with PRMT5 to epigenetically promote IL
      12 expression in innate response.
AB  - Interleukin-12 (IL-12) is critical for induction of protective immunity against
      intracellular bacterial infection. However, the mechanisms for efficient
      induction of IL-12 in innate response remain poorly understood. Here we report
      that the B type of carbonic anhydrase 6 (Car6-b, which encoded CA-VI B) is
      essential for host defense against Listeria monocytogenes (LM) infection by
      epigenetically promoting IL-12 expression independent of its carbonic anhydrase
      activity. Deficiency of Car6-b attenuated IL-12 production upon LM infection both
      in vitro and in vivo. Car6-/- mice were more susceptible to LM infection with
      less production of IL-12. Mechanistically, the nuclear localized CA-VI B
      selectively promotes IL-12 expression by interaction with protein arginine N
      methyltransferase 5 (PRMT5), which reduces symmetric dimethylation of histone H3
      arginine 8 modification (H3R8me2s) at Il12 promoters to facilitate chromatin
      accessibility, selectively enhancing c-Rel binding to the Il12b promoter. Our
      findings add insights to the epigenetic regulation of IL-12 induction in innate
      immunity.

PMID- 28739931
TI  - How language shapes the cultural inheritance of categories.
AB  - It is widely recognized that language plays a key role in the transmission of
      human culture, but relatively little is known about the mechanisms by which
      language simultaneously encourages both cultural stability and cultural
      innovation. This paper examines this issue by focusing on the use of language to
      transmit categories, focusing on two universal devices: labels (e.g., shark,
      woman) and generics (e.g., "sharks attack swimmers"; "women are nurturing"). We
      propose that labels and generics each assume two key principles: norms and
      essentialism. The normative assumption permits transmission of category
      information with great fidelity, whereas essentialism invites innovation by means
      of an open-ended, placeholder structure. Additionally, we sketch out how labels
      and generics aid in conceptual alignment and the progressive "looping" between
      categories and cultural practices. In this way, human language is a technology
      that enhances and expands the categorization capacities that we share with other
      animals.

PMID- 28739932
TI  - CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid
      droplet abundance and stimulation of fatty acid oxidation.
AB  - Triple-negative breast cancer (TNBC) is notoriously aggressive with high
      metastatic potential, which has recently been linked to high rates of fatty acid
      oxidation (FAO). Here we report the mechanism of lipid metabolism dysregulation
      in TNBC through the prometastatic protein, CUB-domain containing protein 1
      (CDCP1). We show that a "low-lipid" phenotype is characteristic of breast cancer
      cells compared with normal breast epithelial cells and negatively correlates with
      invasiveness in 3D culture. Using coherent anti-Stokes Raman scattering and two
      photon excited fluorescence microscopy, we show that CDCP1 depletes lipids from
      cytoplasmic lipid droplets (LDs) through reduced acyl-CoA production and
      increased lipid utilization in the mitochondria through FAO, fueling oxidative
      phosphorylation. These findings are supported by CDCP1's interaction with and
      inhibition of acyl CoA-synthetase ligase (ACSL) activity. Importantly, CDCP1
      knockdown increases LD abundance and reduces TNBC 2D migration in vitro, which
      can be partially rescued by the ACSL inhibitor, Triacsin C. Furthermore, CDCP1
      knockdown reduced 3D invasion, which can be rescued by ACSL3 co-knockdown. In
      vivo, inhibiting CDCP1 activity with an engineered blocking fragment
      (extracellular portion of cleaved CDCP1) lead to increased LD abundance in
      primary tumors, decreased metastasis, and increased ACSL activity in two animal
      models of TNBC. Finally, TNBC lung metastases have lower LD abundance than their
      corresponding primary tumors, indicating that LD abundance in primary tumor might
      serve as a prognostic marker for metastatic potential. Our studies have important
      implications for the development of TNBC therapeutics to specifically block CDCP1
      driven FAO and oxidative phosphorylation, which contribute to TNBC migration and
      metastasis.

PMID- 28739933
TI  - Structural organization of the actin-spectrin-based membrane skeleton in
      dendrites and soma of neurons.
AB  - Actin, spectrin, and associated molecules form a membrane-associated periodic
      skeleton (MPS) in neurons. In the MPS, short actin filaments, capped by actin
      capping proteins, form ring-like structures that wrap around the circumference of
      neurites, and these rings are periodically spaced along the neurite by spectrin
      tetramers, forming a quasi-1D lattice structure. This 1D MPS structure was
      initially observed in axons and exists extensively in axons, spanning nearly the
      entire axonal shaft of mature neurons. Such 1D MPS was also observed in
      dendrites, but the extent to which it exists and how it develops in dendrites
      remain unclear. It is also unclear whether other structural forms of the membrane
      skeleton are present in neurons. Here, we investigated the spatial organizations
      of spectrin, actin, and adducin, an actin-capping protein, in the dendrites and
      soma of cultured hippocampal neurons at different developmental stages, and
      compared results with those obtained in axons, using superresolution imaging. We
      observed that the 1D MPS exists in a substantial fraction of dendritic regions in
      relatively mature neurons, but this structure develops slower and forms with a
      lower propensity in dendrites than in axons. In addition, we observed that
      spectrin, actin, and adducin also form a 2D polygonal lattice structure,
      resembling the expanded erythrocyte membrane skeleton structure, in the
      somatodendritic compartment. This 2D lattice structure also develops
      substantially more slowly in the soma and dendrites than the development of the
      1D MPS in axons. These results suggest membrane skeleton structures are
      differentially regulated across different subcompartments of neurons.

PMID- 28739934
TI  - Crossover from band-like to thermally activated charge transport in organic
      transistors due to strain-induced traps.
AB  - The temperature dependence of the charge-carrier mobility provides essential
      insight into the charge transport mechanisms in organic semiconductors. Such
      knowledge imparts critical understanding of the electrical properties of these
      materials, leading to better design of high-performance materials for consumer
      applications. Here, we present experimental results that suggest that the
      inhomogeneous strain induced in organic semiconductor layers by the mismatch
      between the coefficients of thermal expansion (CTE) of the consecutive device
      layers of field-effect transistors generates trapping states that localize charge
      carriers. We observe a universal scaling between the activation energy of the
      transistors and the interfacial thermal expansion mismatch, in which band-like
      transport is observed for similar CTEs, and activated transport otherwise. Our
      results provide evidence that a high-quality semiconductor layer is necessary,
      but not sufficient, to obtain efficient charge-carrier transport in devices, and
      underline the importance of holistic device design to achieve the intrinsic
      performance limits of a given organic semiconductor. We go on to show that
      insertion of an ultrathin CTE buffer layer mitigates this problem and can help
      achieve band-like transport on a wide range of substrate platforms.

PMID- 28739935
TI  - Dehumanization increases instrumental violence, but not moral violence.
AB  - Across five experiments, we show that dehumanization-the act of perceiving
      victims as not completely human-increases instrumental, but not moral, violence.
      In attitude surveys, ascribing reduced capacities for cognitive, experiential,
      and emotional states to victims predicted support for practices where victims are
      harmed to achieve instrumental goals, including sweatshop labor, animal
      experimentation, and drone strikes that result in civilian casualties, but not
      practices where harm is perceived as morally righteous, including capital
      punishment, killing in war, and drone strikes that kill terrorists. In vignette
      experiments, using dehumanizing compared with humanizing language increased
      participants' willingness to harm strangers for money, but not participants'
      willingness to harm strangers for their immoral behavior. Participants also
      spontaneously dehumanized strangers when they imagined harming them for money,
      but not when they imagined harming them for their immoral behavior. Finally,
      participants humanized strangers who were low in humanity if they imagined
      harming them for immoral behavior, but not money, suggesting that morally
      motivated perpetrators may humanize victims to justify violence against them. Our
      findings indicate that dehumanization enables violence that perpetrators see as
      unethical, but instrumentally beneficial. In contrast, dehumanization does not
      contribute to moral violence because morally motivated perpetrators wish to harm
      complete human beings who are capable of deserving blame, experiencing suffering,
      and understanding its meaning.

PMID- 28739936
TI  - Gene-culture coevolution in whales and dolphins.
AB  - Whales and dolphins (Cetacea) have excellent social learning skills as well as a
      long and strong mother-calf bond. These features produce stable cultures, and, in
      some species, sympatric groups with different cultures. There is evidence and
      speculation that this cultural transmission of behavior has affected gene
      distributions. Culture seems to have driven killer whales into distinct ecotypes,
      which may be incipient species or subspecies. There are ecotype-specific signals
      of selection in functional genes that correspond to cultural foraging behavior
      and habitat use by the different ecotypes. The five species of whale with
      matrilineal social systems have remarkably low diversity of mtDNA. Cultural
      hitchhiking, the transmission of functionally neutral genes in parallel with
      selective cultural traits, is a plausible hypothesis for this low diversity,
      especially in sperm whales. In killer whales the ecotype divisions, together with
      founding bottlenecks, selection, and cultural hitchhiking, likely explain the low
      mtDNA diversity. Several cetacean species show habitat-specific distributions of
      mtDNA haplotypes, probably the result of mother-offspring cultural transmission
      of migration routes or destinations. In bottlenose dolphins, remarkable small
      scale differences in haplotype distribution result from maternal cultural
      transmission of foraging methods, and large-scale redistributions of sperm whale
      cultural clans in the Pacific have likely changed mitochondrial genetic
      geography. With the acceleration of genomics new results should come fast, but
      understanding gene-culture coevolution will be hampered by the measured pace of
      research on the socio-cultural side of cetacean biology.

PMID- 28739937
TI  - Why eyewitnesses fail.
AB  - Eyewitness identifications play an important role in the investigation and
      prosecution of crimes, but it is well known that eyewitnesses make mistakes,
      often with serious consequences. In light of these concerns, the National Academy
      of Sciences recently convened a panel of experts to undertake a comprehensive
      study of current practice and use of eyewitness testimony, with an eye toward
      understanding why identification errors occur and what can be done to prevent
      them. The work of this committee led to key findings and recommendations for
      reform, detailed in a consensus report entitled Identifying the Culprit:
      Assessing Eyewitness Identification In this review, I focus on the scientific
      issues that emerged from this study, along with brief discussions of how these
      issues led to specific recommendations for additional research, best practices
      for law enforcement, and use of eyewitness evidence by the courts.

PMID- 28739938
TI  - The evolution of cognitive mechanisms in response to cultural innovations.
AB  - When humans and other animals make cultural innovations, they also change their
      environment, thereby imposing new selective pressures that can modify their
      biological traits. For example, there is evidence that dairy farming by humans
      favored alleles for adult lactose tolerance. Similarly, the invention of cooking
      possibly affected the evolution of jaw and tooth morphology. However, when it
      comes to cognitive traits and learning mechanisms, it is much more difficult to
      determine whether and how their evolution was affected by culture or by their use
      in cultural transmission. Here we argue that, excluding very recent cultural
      innovations, the assumption that culture shaped the evolution of cognition is
      both more parsimonious and more productive than assuming the opposite. In
      considering how culture shapes cognition, we suggest that a process-level model
      of cognitive evolution is necessary and offer such a model. The model employs
      relatively simple coevolving mechanisms of learning and data acquisition that
      jointly construct a complex network of a type previously shown to be capable of
      supporting a range of cognitive abilities. The evolution of cognition, and thus
      the effect of culture on cognitive evolution, is captured through small
      modifications of these coevolving learning and data-acquisition mechanisms, whose
      coordinated action is critical for building an effective network. We use the
      model to show how these mechanisms are likely to evolve in response to cultural
      phenomena, such as language and tool-making, which are associated with major
      changes in data patterns and with new computational and statistical challenges.

PMID- 28739939
TI  - Implications of life-history strategies for obesity.
AB  - The association between low socioeconomic status (SES) and obesity is well
      documented. In the current research, a life history theory (LHT) framework
      provided an explanation for this association. Derived from evolutionary
      behavioral science, LHT emphasizes how variability in exposure to
      unpredictability during childhood gives rise to individual differences in a range
      of social psychological processes across the life course. Consistent with
      previous LHT research, the current findings suggest that exposure to
      unpredictability during childhood (a characteristic common to low SES
      environments) is associated with the adoption of a fast life-history strategy,
      one marked by impulsivity and a focus on short-term goals. We demonstrate that a
      fast life-history strategy, in turn, was associated with dysregulated weight
      management behaviors (i.e., eating even in the absence of hunger), which were
      predictive of having a high body mass index (BMI) and being obese. In both
      studies, findings held while controlling for participants' current socioeconomic
      status, suggesting that obesity is rooted in childhood experiences. A serial
      mediation model in study 2 confirmed that effects of childhood SES on adult BMI
      and obesity can be explained in part by exposure to unpredictability, the
      adoption of a fast life-history strategy, and dysregulated-eating behaviors.
      These findings suggest that weight problems in adulthood may be rooted partially
      in early childhood exposure to unpredictable events and environments. LHT
      provides a valuable explanatory framework for understanding the root causes of
      obesity.

PMID- 28739940
TI  - Song hybridization events during revolutionary song change provide insights into
      cultural transmission in humpback whales.
AB  - Cultural processes occur in a wide variety of animal taxa, from insects to
      cetaceans. The songs of humpback whales are one of the most striking examples of
      the transmission of a cultural trait and social learning in any nonhuman animal.
      To understand how songs are learned, we investigate rare cases of song
      hybridization, where parts of an existing song are spliced with a new one, likely
      before an individual totally adopts the new song. Song unit sequences were
      extracted from over 9,300 phrases recorded during two song revolutions across the
      South Pacific Ocean, allowing fine-scale analysis of composition and sequencing.
      In hybrid songs the current and new songs were spliced together in two specific
      ways: (i) singers placed a single hybrid phrase, in which content from both songs
      were combined, between the two song types when transitioning from one to the
      other, and/or (ii) singers spliced complete themes from the revolutionary song
      into the current song. Sequence analysis indicated that both processes were
      governed by structural similarity rules. Hybrid phrases or theme substitutions
      occurred at points in the songs where both songs contained "similar sounds
      arranged in a similar pattern." Songs appear to be learned as segments
      (themes/phrase types), akin to birdsong and human language acquisition, and these
      can be combined in predictable ways if the underlying structural pattern is
      similar. These snapshots of song change provide insights into the mechanisms
      underlying song learning in humpback whales, and comparative perspectives on the
      evolution of human language and culture.

PMID- 28739941
TI  - Cultural evolutionary theory: How culture evolves and why it matters.
AB  - Human cultural traits-behaviors, ideas, and technologies that can be learned from
      other individuals-can exhibit complex patterns of transmission and evolution, and
      researchers have developed theoretical models, both verbal and mathematical, to
      facilitate our understanding of these patterns. Many of the first quantitative
      models of cultural evolution were modified from existing concepts in theoretical
      population genetics because cultural evolution has many parallels with, as well
      as clear differences from, genetic evolution. Furthermore, cultural and genetic
      evolution can interact with one another and influence both transmission and
      selection. This interaction requires theoretical treatments of gene-culture
      coevolution and dual inheritance, in addition to purely cultural evolution. In
      addition, cultural evolutionary theory is a natural component of studies in
      demography, human ecology, and many other disciplines. Here, we review the core
      concepts in cultural evolutionary theory as they pertain to the extension of
      biology through culture, focusing on cultural evolutionary applications in
      population genetics, ecology, and demography. For each of these disciplines, we
      review the theoretical literature and highlight relevant empirical studies. We
      also discuss the societal implications of the study of cultural evolution and of
      the interactions of humans with one another and with their environment.

PMID- 28739943
TI  - Conformity does not perpetuate suboptimal traditions in a wild population of
      songbirds.
AB  - Social learning is important to the life history of many animals, helping
      individuals to acquire new adaptive behavior. However despite long-running
      debate, it remains an open question whether a reliance on social learning can
      also lead to mismatched or maladaptive behavior. In a previous study, we
      experimentally induced traditions for opening a bidirectional door puzzle box in
      replicate subpopulations of the great tit Parus major Individuals were conformist
      social learners, resulting in stable cultural behaviors. Here, we vary the
      rewards gained by these techniques to ask to what extent established behaviors
      are flexible to changing conditions. When subpopulations with established
      foraging traditions for one technique were subjected to a reduced foraging
      payoff, 49% of birds switched their behavior to a higher-payoff foraging
      technique after only 14 days, with younger individuals showing a faster rate of
      change. We elucidated the decision-making process for each individual, using a
      mechanistic learning model to demonstrate that, perhaps surprisingly, this
      population-level change was achieved without significant asocial exploration and
      without any evidence for payoff-biased copying. Rather, by combining conformist
      social learning with payoff-sensitive individual reinforcement (updating of
      experience), individuals and populations could both acquire adaptive behavior and
      track environmental change.

PMID- 28739942
TI  - Lipophilic siRNA targets albumin in situ and promotes bioavailability, tumor
      penetration, and carrier-free gene silencing.
AB  - Clinical translation of therapies based on small interfering RNA (siRNA) is
      hampered by siRNA's comprehensively poor pharmacokinetic properties, which
      necessitate molecule modifications and complex delivery strategies. We sought an
      alternative approach to commonly used nanoparticle carriers by leveraging the
      long-lived endogenous serum protein albumin as an siRNA carrier. We synthesized
      siRNA conjugated to a diacyl lipid moiety (siRNA-L2), which rapidly binds albumin
      in situ. siRNA-L2, in comparison with unmodified siRNA, exhibited a 5.7-fold
      increase in circulation half-life, an 8.6-fold increase in bioavailability, and
      reduced renal accumulation. Benchmarked against leading commercial siRNA
      nanocarrier in vivo jetPEI, siRNA-L2 achieved 19-fold greater tumor accumulation
      and 46-fold increase in per-tumor-cell uptake in a mouse orthotopic model of
      human triple-negative breast cancer. siRNA-L2 penetrated tumor tissue rapidly and
      homogeneously; 30 min after i.v. injection, siRNA-L2 achieved uptake in 99% of
      tumor cells, compared with 60% for jetPEI. Remarkably, siRNA-L2 achieved a
      tumor:liver accumulation ratio >40:1 vs. <3:1 for jetPEI. The improved
      pharmacokinetic properties of siRNA-L2 facilitated significant tumor gene
      silencing for 7 d after two i.v. doses. Proof-of-concept was extended to a
      patient-derived xenograft model, in which jetPEI tumor accumulation was reduced
      fourfold relative to the same formulation in the orthotopic model. The siRNA-L2
      tumor accumulation diminished only twofold, suggesting that the superior tumor
      distribution of the conjugate over nanoparticles will be accentuated in clinical
      situations. These data reveal the immense promise of in situ albumin targeting
      for development of translational, carrier-free RNAi-based cancer therapies.

PMID- 28739944
TI  - Synchronized practice helps bearded capuchin monkeys learn to extend attention
      while learning a tradition.
AB  - Culture extends biology in that the setting of development shapes the traditions
      that individuals learn, and over time, traditions evolve as occasional variations
      are learned by others. In humans, interactions with others impact the development
      of cognitive processes, such as sustained attention, that shape how individuals
      learn as well as what they learn. Thus, learning itself is impacted by culture.
      Here, we explore how social partners might shape the development of psychological
      processes impacting learning a tradition. We studied bearded capuchin monkeys
      learning a traditional tool-using skill, cracking nuts using stone hammers. Young
      monkeys practice components of cracking nuts with stones for years before
      achieving proficiency. We examined the time course of young monkeys' activity
      with nuts before, during, and following others' cracking nuts. Results
      demonstrate that the onset of others' cracking nuts immediately prompts young
      monkeys to start handling and percussing nuts, and they continue these activities
      while others are cracking. When others stop cracking nuts, young monkeys sustain
      the uncommon actions of percussing and striking nuts for shorter periods than the
      more common actions of handling nuts. We conclude that nut-cracking by adults can
      promote the development of sustained attention for the critical but less common
      actions that young monkeys must practice to learn this traditional skill. This
      work suggests that in nonhuman species, as in humans, socially specified settings
      of development impact learning processes as well as learning outcomes. Nonhumans,
      like humans, may be culturally variable learners.

PMID- 28739945
TI  - Cumulative cultural learning: Development and diversity.
AB  - The complexity and variability of human culture is unmatched by any other
      species. Humans live in culturally constructed niches filled with artifacts,
      skills, beliefs, and practices that have been inherited, accumulated, and
      modified over generations. A causal account of the complexity of human culture
      must explain its distinguishing characteristics: It is cumulative and highly
      variable within and across populations. I propose that the psychological
      adaptations supporting cumulative cultural transmission are universal but are
      sufficiently flexible to support the acquisition of highly variable behavioral
      repertoires. This paper describes variation in the transmission practices
      (teaching) and acquisition strategies (imitation) that support cumulative
      cultural learning in childhood. Examining flexibility and variation in caregiver
      socialization and children's learning extends our understanding of evolution in
      living systems by providing insight into the psychological foundations of
      cumulative cultural transmission-the cornerstone of human cultural diversity.

PMID- 28739946
TI  - Older, sociable capuchins (Cebus capucinus) invent more social behaviors, but
      younger monkeys innovate more in other contexts.
AB  - An important extension to our understanding of evolutionary processes has been
      the discovery of the roles that individual and social learning play in creating
      recurring phenotypes on which selection can act. Cultural change occurs chiefly
      through invention of new behavioral variants combined with social transmission of
      the novel behaviors to new practitioners. Therefore, understanding what makes
      some individuals more likely to innovate and/or transmit new behaviors is
      critical for creating realistic models of culture change. The difficulty in
      identifying what behaviors qualify as new in wild animal populations has
      inhibited researchers from understanding the characteristics of behavioral
      innovations and innovators. Here, we present the findings of a long-term,
      systematic study of innovation (10 y, 10 groups, and 234 individuals) in wild
      capuchin monkeys (Cebus capucinus) in Lomas Barbudal, Costa Rica. Our methodology
      explicitly seeks novel behaviors, requiring their absence during the first 5 y of
      the study to qualify as novel in the second 5 y of the study. Only about 20% of
      187 innovations identified were retained in innovators' individual behavioral
      repertoires, and 22% were subsequently seen in other group members. Older, more
      social monkeys were more likely to invent new forms of social interaction,
      whereas younger monkeys were more likely to innovate in other behavioral domains
      (foraging, investigative, and self-directed behaviors). Sex and rank had little
      effect on innovative tendencies. Relative to apes, capuchins devote more of their
      innovations repertoire to investigative behaviors and social bonding behaviors
      and less to foraging and comfort behaviors.

PMID- 28739947
TI  - Morphologies of synaptic protein membrane fusion interfaces.
AB  - Neurotransmitter release is orchestrated by synaptic proteins, such as SNAREs,
      synaptotagmin, and complexin, but the molecular mechanisms remain unclear. We
      visualized functionally active synaptic proteins reconstituted into
      proteoliposomes and their interactions in a native membrane environment by
      electron cryotomography with a Volta phase plate for improved resolvability. The
      images revealed individual synaptic proteins and synaptic protein complex
      densities at prefusion contact sites between membranes. We observed distinct
      morphologies of individual synaptic proteins and their complexes. The minimal
      system, consisting of neuronal SNAREs and synaptotagmin-1, produced point and
      long-contact prefusion states. Morphologies and populations of these states
      changed as the regulatory factors complexin and Munc13 were added. Complexin
      increased the membrane separation, along with a higher propensity of point
      contacts. Further inclusion of the priming factor Munc13 exclusively restricted
      prefusion states to point contacts, all of which efficiently fused upon Ca2+
      triggering. We conclude that synaptic proteins have evolved to limit possible
      contact site assemblies and morphologies to those that promote fast Ca2+
      triggered release.

PMID- 28739948
TI  - Synthetic quorum sensing in model microcapsule colonies.
AB  - Biological quorum sensing refers to the ability of cells to gauge their
      population density and collectively initiate a new behavior once a critical
      density is reached. Designing synthetic materials systems that exhibit quorum
      sensing-like behavior could enable the fabrication of devices with both self
      recognition and self-regulating functionality. Herein, we develop models for a
      colony of synthetic microcapsules that communicate by producing and releasing
      signaling molecules. Production of the chemicals is regulated by a biomimetic
      negative feedback loop, the "repressilator" network. Through theory and
      simulation, we show that the chemical behavior of such capsules is sensitive to
      both the density and number of capsules in the colony. For example, decreasing
      the spacing between a fixed number of capsules can trigger a transition in
      chemical activity from the steady, repressed state to large-amplitude
      oscillations in chemical production. Alternatively, for a fixed density, an
      increase in the number of capsules in the colony can also promote a transition
      into the oscillatory state. This configuration-dependent behavior of the capsule
      colony exemplifies quorum-sensing behavior. Using our theoretical model, we
      predict the transitions from the steady state to oscillatory behavior as a
      function of the colony size and capsule density.

PMID- 28739949
TI  - Structural basis of kindlin-mediated integrin recognition and activation.
AB  - Kindlins and talins are integrin-binding proteins that are critically involved in
      integrin activation, an essential process for many fundamental cellular
      activities including cell-matrix adhesion, migration, and proliferation. As FERM
      domain-containing proteins, talins and kindlins, respectively, bind different
      regions of beta-integrin cytoplasmic tails. However, compared with the
      extensively studied talin, little is known about how kindlins specifically
      interact with integrins and synergistically enhance their activation by talins.
      Here, we determined crystal structures of kindlin2 in the apo-form and the beta1-
      and beta3-integrin bound forms. The apo-structure shows an overall architecture
      distinct from talins. The complex structures reveal a unique integrin recognition
      mode of kindlins, which combines two binding motifs to provide specificity that
      is essential for integrin activation and signaling. Strikingly, our structures
      uncover an unexpected dimer formation of kindlins. Interrupting dimer formation
      impairs kindlin-mediated integrin activation. Collectively, the structural,
      biochemical, and cellular results provide mechanistic explanations that account
      for the effects of kindlins on integrin activation as well as for how kindlin
      mutations found in patients with Kindler syndrome and leukocyte-adhesion
      deficiency may impact integrin-mediated processes.

PMID- 28739950
TI  - Coevolution of cultural intelligence, extended life history, sociality, and brain
      size in primates.
AB  - Explanations for primate brain expansion and the evolution of human cognition and
      culture remain contentious despite extensive research. While multiple comparative
      analyses have investigated variation in brain size across primate species, very
      few have addressed why primates vary in how much they use social learning. Here,
      we evaluate the hypothesis that the enhanced reliance on socially transmitted
      behavior observed in some primates has coevolved with enlarged brains, complex
      sociality, and extended lifespans. Using recently developed phylogenetic
      comparative methods we show that, across primate species, a measure of social
      learning proclivity increases with absolute and relative brain volume, longevity
      (specifically reproductive lifespan), and social group size, correcting for
      research effort. We also confirm relationships of absolute and relative brain
      volume with longevity (both juvenile period and reproductive lifespan) and social
      group size, although longevity is generally the stronger predictor. Relationships
      between social learning, brain volume, and longevity remain when controlling for
      maternal investment and are therefore not simply explained as a by-product of the
      generally slower life history expected for larger brained species. Our findings
      suggest that both brain expansion and high reliance on culturally transmitted
      behavior coevolved with sociality and extended lifespan in primates. This
      coevolution is consistent with the hypothesis that the evolution of large brains,
      sociality, and long lifespans has promoted reliance on culture, with reliance on
      culture in turn driving further increases in brain volume, cognitive abilities,
      and lifespans in some primate lineages.

PMID- 28739951
TI  - Bidirectional manipulation of mTOR signaling disrupts socially mediated vocal
      learning in juvenile songbirds.
AB  - Early life experiences can have long-lasting behavioral consequences because they
      are encoded when the brain is most malleable. The mechanistic target of rapamycin
      (mTOR) signaling cascade modulates experience-dependent synaptic plasticity,
      among other processes. mTOR has been almost exclusively examined in adult rodent
      learning models, but may be especially important in organizing neural circuits
      required for developmental acquisition of meaningful complex behaviors. It is
      among the most commonly implicated factors in neurodevelopmental autism spectrum
      disorders (ASD), characterized, in part, by distinct social and communication
      phenotypes. Here, we investigated mTOR in juvenile zebra finch songbirds. Much as
      children learn language, young male zebra finches need to interact socially with
      an adult tutor to learn a meaningful song. The memory of the tutor's song
      structure guides the juvenile's own song, which it uses to communicate for the
      rest of its life. We hypothesized that mTOR is required for juveniles to learn
      song. To this end, we first discovered that hearing song activates mTOR signaling
      in a brain area required for tutor song memorization in males old enough to copy
      song but not in younger males or females, who cannot sing. We then showed that
      both inhibition and constitutive activation of mTOR during tutor experiences
      significantly diminished tutor song copying. Finally, we found that constitutive
      mTOR activation lowered a behavioral measure of the juvenile's social engagement
      during tutor experiences, mirroring the relationship in humans. These studies
      therefore advance understanding about the effects of experience in the context of
      neurodevelopmental disorders and typical neural development.

PMID- 28739952
TI  - Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self
      polymerization and membrane association.
AB  - Many enveloped viruses encode a matrix protein. In the influenza A virus, the
      matrix protein M1 polymerizes into a rigid protein layer underneath the viral
      envelope to help enforce the shape and structural integrity of intact viruses.
      The influenza virus M1 is also known to mediate virus budding as well as the
      nuclear export of the viral nucleocapsids and their subsequent packaging into
      nascent viral particles. Despite extensive studies on the influenza A virus M1
      (FLUA-M1), only crystal structures of its N-terminal domain are available. Here
      we report the crystal structure of the full-length M1 from another orthomyxovirus
      that infects fish, the infectious salmon anemia virus (ISAV). The structure of
      ISAV-M1 assumes the shape of an elbow, with its N domain closely resembling that
      of the FLUA-M1. The C domain, which is connected to the N domain through a
      flexible linker, is made of four alpha-helices packed as a tight bundle. In the
      crystal, ISAV-M1 monomers form infinite 2D arrays with a network of interactions
      involving both the N and C domains. Results from liposome flotation assays
      indicated that ISAV-M1 binds membrane via electrostatic interactions that are
      primarily mediated by a positively charged surface loop from the N domain.
      Cryoelectron tomography reconstruction of intact ISA virions identified a matrix
      protein layer adjacent to the inner leaflet of the viral membrane. The physical
      dimensions of the virion-associated matrix layer are consistent with the 2D ISAV
      M1 crystal lattice, suggesting that the crystal lattice is a valid model for
      studying M1-M1, M1-membrane, and M1-RNP interactions in the virion.

PMID- 28739953
TI  - Protein nanocages that penetrate airway mucus and tumor tissue.
AB  - Reports on drug delivery systems capable of overcoming multiple biological
      barriers are rare. We introduce a nanoparticle-based drug delivery technology
      capable of rapidly penetrating both lung tumor tissue and the mucus layer that
      protects airway tissues from nanoscale objects. Specifically, human ferritin
      heavy-chain nanocages (FTn) were functionalized with polyethylene glycol (PEG) in
      a unique manner that allows robust control over PEG location (nanoparticle
      surface only) and surface density. We varied PEG surface density and molecular
      weight to discover PEGylated FTn that rapidly penetrated both mucus barriers and
      tumor tissues in vitro and in vivo. Upon inhalation in mice, PEGylated FTn with
      optimized PEGylation rapidly penetrated the mucus gel layer and thus provided a
      uniform distribution throughout the airways. Subsequently, PEGylated FTn
      preferentially penetrated and distributed within orthotopic lung tumor tissue,
      and selectively entered cancer cells, in a transferrin receptor 1-dependent
      manner, which is up-regulated in most cancers. To test the potential therapeutic
      benefits, doxorubicin (DOX) was conjugated to PEGylated FTn via an acid-labile
      linker to facilitate intracellular release of DOX after cell entry. Inhalation of
      DOX-loaded PEGylated FTn led to 60% survival, compared with 10% survival in the
      group that inhaled DOX in solution at the maximally tolerated dose, in a murine
      model of malignant airway lung cancer. This approach may provide benefits as an
      adjuvant therapy combined with systemic chemo- or immunotherapy or as a stand
      alone therapy for patients with tumors confined to the airways.

PMID- 28739954
TI  - Revised M06-L functional for improved accuracy on chemical reaction barrier
      heights, noncovalent interactions, and solid-state physics.
AB  - We present the revM06-L functional, which we designed by optimizing against a
      larger database than had been used for Minnesota 2006 local functional (M06-L)
      and by using smoothness restraints. The optimization strategy reduced the number
      of parameters from 34 to 31 because we removed some large terms that increased
      the required size of the quadrature grid and the number of self-consistent-field
      iterations. The mean unsigned error (MUE) of revM06-L on 422 chemical energies is
      3.07 kcal/mol, which is improved from 3.57 kcal/mol calculated by M06-L. The MUE
      of revM06-L for the chemical reaction barrier height database (BH76) is 1.98
      kcal/mol, which is improved by more than a factor of 2 with respect to the M06-L
      functional. The revM06-L functional gives the best result among local functionals
      tested for the noncovalent interaction database (NC51), with an MUE of only 0.36
      kcal/mol, and the MUE of revM06-L for the solid-state lattice constant database
      (LC17) is half that for M06-L. The revM06-L functional also yields smoother
      potential curves, and it predicts more-accurate results than M06-L for seven out
      of eight diversified test sets not used for parameterization. We conclude that
      the revM06-L functional is well suited for a broad range of applications in
      chemistry and condensed-matter physics.

PMID- 28739956
TI  - Cavitation onset caused by acceleration.
AB  - Striking the top of a liquid-filled bottle can shatter the bottom. An intuitive
      interpretation of this event might label an impulsive force as the culprit in
      this fracturing phenomenon. However, high-speed photography reveals the formation
      and collapse of tiny bubbles near the bottom before fracture. This observation
      indicates that the damaging phenomenon of cavitation is at fault. Cavitation is
      well known for causing damage in various applications including pipes and ship
      propellers, making accurate prediction of cavitation onset vital in several
      industries. However, the conventional cavitation number as a function of velocity
      incorrectly predicts the cavitation onset caused by acceleration. This
      unexplained discrepancy leads to the derivation of an alternative dimensionless
      term from the equation of motion, predicting cavitation as a function of
      acceleration and fluid depth rather than velocity. Two independent research
      groups in different countries have tested this theory; separate series of
      experiments confirm that an alternative cavitation number, presented in this
      paper, defines the universal criteria for the onset of acceleration-induced
      cavitation.

PMID- 28739955
TI  - Lipid rafts sense and direct electric field-induced migration.
AB  - Endogenous electric fields (EFs) are involved in developmental regulation and
      wound healing. Although the phenomenon is known for more than a century, it is
      not clear how cells perceive the external EF. Membrane proteins, responding to
      electrophoretic and electroosmotic forces, have long been proposed as the sensing
      molecules. However, specific charge modification of surface proteins did not
      change cell migration motility nor directionality in EFs. Moreover, symmetric
      alternating current (AC) EF directs cell migration in a frequency-dependent
      manner. Due to their charge and ability to coalesce, glycolipids are therefore
      the likely primary EF sensor driving polarization of membrane proteins and
      intracellular signaling. We demonstrate that detergent-resistant membrane
      nanodomains, also known as lipid rafts, are the primary response element in EF
      sensing. The clustering and activation of caveolin and signaling proteins further
      stabilize raft structure and feed-forward downstream signaling events, such as
      rho and PI3K activation. Theoretical modeling supports the experimental results
      and predicts AC frequency-dependent cell and raft migration. Our results
      establish a fundamental mechanism for cell electrosensing and provide a role in
      lipid raft mechanotransduction.

PMID- 28739957
TI  - A social insect perspective on the evolution of social learning mechanisms.
AB  - The social world offers a wealth of opportunities to learn from others, and
      across the animal kingdom individuals capitalize on those opportunities. Here, we
      explore the role of natural selection in shaping the processes that underlie
      social information use, using a suite of experiments on social insects as case
      studies. We illustrate how an associative framework can encompass complex,
      context-specific social learning in the insect world and beyond, and based on the
      hypothesis that evolution acts to modify the associative process, suggest
      potential pathways by which social information use could evolve to become more
      efficient and effective. Social insects are distant relatives of vertebrate
      social learners, but the research we describe highlights routes by which natural
      selection could coopt similar cognitive raw material across the animal kingdom.

PMID- 28739958
TI  - Neural basis for hand muscle synergies in the primate spinal cord.
AB  - Grasping is a highly complex movement that requires the coordination of multiple
      hand joints and muscles. Muscle synergies have been proposed to be the functional
      building blocks that coordinate such complex motor behaviors, but little is known
      about how they are implemented in the central nervous system. Here we demonstrate
      that premotor interneurons (PreM-INs) in the primate cervical spinal cord
      underlie the spatiotemporal patterns of hand muscle synergies during a voluntary
      grasping task. Using spike-triggered averaging of hand muscle activity, we found
      that the muscle fields of PreM-INs were not uniformly distributed across hand
      muscles but rather distributed as clusters corresponding to muscle synergies.
      Moreover, although individual PreM-INs have divergent activation patterns, the
      population activity of PreM-INs reflects the temporal activation of muscle
      synergies. These findings demonstrate that spinal PreM-INs underlie the muscle
      coordination required for voluntary hand movements in primates. Given the
      evolution of neural control of primate hand functions, we suggest that spinal
      premotor circuits provide the fundamental coordination of multiple joints and
      muscles upon which more fractionated control is achieved by superimposed,
      phylogenetically newer, pathways.

PMID- 28739959
TI  - Young children communicate their ignorance and ask questions.
AB  - Children acquire information, especially about the culture in which they are
      being raised, by listening to other people. Recent evidence has shown that young
      children are selective learners who preferentially accept information, especially
      from informants who are likely to be representative of the surrounding culture.
      However, the extent to which children understand this process of information
      transmission and actively exploit it to fill gaps in their knowledge has not been
      systematically investigated. We review evidence that toddlers exhibit various
      expressive behaviors when faced with knowledge gaps. They look toward an
      available adult, convey ignorance via nonverbal gestures (flips/shrugs), and
      increasingly produce verbal acknowledgments of ignorance ("I don't know"). They
      also produce comments and questions about what their interlocutors might know and
      adopt an interrogative stance toward them. Thus, in the second and third years,
      children actively seek information from interlocutors via nonverbal gestures or
      verbal questions and display a heightened tendency to encode and retain such
      sought-after information.

PMID- 28739960
TI  - Cultural macroevolution matters.
AB  - Evolutionary thinking can be applied to both cultural microevolution and
      macroevolution. However, much of the current literature focuses on cultural
      microevolution. In this article, we argue that the growing availability of large
      cross-cultural datasets facilitates the use of computational methods derived from
      evolutionary biology to answer broad-scale questions about the major transitions
      in human social organization. Biological methods can be extended to human
      cultural evolution. We illustrate this argument with examples drawn from our
      recent work on the roles of Big Gods and ritual human sacrifice in the evolution
      of large, stratified societies. These analyses show that, although the presence
      of Big Gods is correlated with the evolution of political complexity, in
      Austronesian cultures at least, they do not play a causal role in ratcheting up
      political complexity. In contrast, ritual human sacrifice does play a causal role
      in promoting and sustaining the evolution of stratified societies by maintaining
      and legitimizing the power of elites. We briefly discuss some common objections
      to the application of phylogenetic modeling to cultural evolution and argue that
      the use of these methods does not require a commitment to either gene-like
      cultural inheritance or to the view that cultures are like vertebrate species. We
      conclude that the careful application of these methods can substantially enhance
      the prospects of an evolutionary science of human history.

PMID- 28739961
TI  - Frustration across the periodic table: heterolytic cleavage of dihydrogen by
      metal complexes.
AB  - This perspective examines frustrated Lewis pairs (FLPs) in the context of
      heterolytic cleavage of H2 by transition metal complexes, with an emphasis on
      molecular complexes bearing an intramolecular Lewis base. FLPs have traditionally
      been associated with main group compounds, yet many reactions of transition metal
      complexes support a broader classification of FLPs that includes certain types of
      transition metal complexes with reactivity resembling main group-based FLPs. This
      article surveys transition metal complexes that heterolytically cleave H2, which
      vary in the degree that the Lewis pairs within these systems interact. Many of
      the examples include complexes bearing a pendant amine functioning as the base
      with the metal functioning as the hydride acceptor. Consideration of transition
      metal compounds in the context of FLPs can inspire new innovations and
      improvements in transition metal catalysis.This article is part of the themed
      issue 'Frustrated Lewis pair chemistry'.

PMID- 28739962
TI  - Chemoselective Lewis pair polymerization of renewable multivinyl-functionalized
      gamma-butyrolactones.
AB  - Multivinyl-functionalized gamma-butyrolactones, gamma-vinyl-gamma-methyl-alpha
      methylene-gamma-butyrolactone (gammaVMMBL) and gamma-allyl-gamma-methyl-alpha
      methylene-gamma-butyrolactone (gammaAMMBL), have been synthesized from
      biorenewable ethyl levulinate and effectively polymerized by Lewis pairs
      consisting of an organic N-heterocyclic carbene Lewis base and a strong organo
      Lewis acid E(C6F5)3 (E = Al, B). This Lewis pair polymerization is quantitatively
      chemoselective, proceeds exclusively via polyaddition across the conjugated alpha
      methylene double bond without participation of the gamma-vinyl or gamma-allyl
      double bond, and produces high-molecular-weight functionalized polymers with
      unimodal molecular-weight distributions. The Al-based Lewis pair produces a
      polymer with approximately 5.5 times higher molecular weight than that produced
      by the B-based Lewis pair. The resulting vinyl-functionalized polymers are
      soluble in common organic solvents and stable at room temperature, and can be
      thermally cured into crosslinked materials.This article is part of the themed
      issue 'Frustrated Lewis pair chemistry'.

PMID- 28739963
TI  - On the concept of frustrated Lewis pairs.
AB  - In this concept article, we consider the notion of 'frustrated Lewis pairs'
      (FLPs). While the original use of the term referred to steric inhibition of
      dative bond formation in a Lewis pair, work in the intervening decade
      demonstrates the limitation of this simplistic view. Analogies to known
      transition metal chemistry and the applications in other areas of chemistry are
      considered. In the light of these findings, we present reflections on the
      criteria for a definition of the term 'frustrated Lewis pair'. Segregation of the
      Lewis acid and base and the kinetic nature of FLP reactivity are discussed. We
      are led to the conclusion that, while an all-inclusive definition of FLP is
      challenging, the notion of 'FLP chemistry' is more readily recognized.This
      article is part of the themed issue 'Frustrated Lewis pair chemistry'.

PMID- 28739964
TI  - On the hydrogen activation by frustrated Lewis pairs in the solid state:
      benchmark studies and theoretical insights.
AB  - Recently, the concept of small molecule activation by frustrated Lewis pairs
      (FLPs) has been expanded to the solid state showing a variety of interesting
      reactivities. Therefore, there is a need to establish a computational protocol to
      investigate such systems theoretically. In the present study, we selected several
      FLPs and applied multiple levels of theory, ranging from a semi-empirical tight
      binding Hamiltonian to dispersion corrected hybrid density functionals. Their
      performance is benchmarked for the computation of crystal geometries,
      thermostatistical contributions, and reaction energies. We show that the
      computationally efficient HF-3c method gives accurate crystal structures and is
      numerically stable and sufficiently fast for routine applications. This method
      also gives reliable values for the thermostatistical contributions to Gibbs free
      energies. The meta-generalized gradient approximated TPSS-D3 evaluated in a
      projector augmented plane wave basis set is able to produce sufficiently accurate
      reaction electronic energies. The established protocol is intended to support
      experimental studies and to predict new reactions in the emerging field of solid
      state FLPs.This article is part of the themed issue 'Frustrated Lewis pair
      chemistry'.

PMID- 28739965
TI  - Attempted synthesis of ortho-phenylene phosphino-tritylium cations.
AB  - With the synthesis of ortho-phenylene phosphino-tritylium cations as an
      objective, we generated (2-lithiophenyl)diphenylphosphine and (2-lithiophenyl)di
      isopropylphosphine and allowed these organolithium reagents to react with
      benzophenone. The resulting phosphino-triarylcarbinols were allowed to react with
      HBF4 in the presence of trifluoroacetic anhydride in order to generate the
      corresponding cations. Instead of the targeted ortho-phenylene phosphino
      tritylium, the cations formed in these reactions were identified as the four
      membered phosphonium species 7,7-bis(phenyl)-8,8-bis(phenyl)-7
      phosphoniabicyclo[4.2.0]octa-1,3,5-triene (3+) and 7,7-bis(phenyl)-8,8
      bis(isopropyl)-7-phosphoniabicyclo[4.2.0]octa-1,3,5-triene (4+), which were both
      isolated as tetrafluoroborate salts. The structure of these compounds has been
      confirmed by X-ray analysis. These new cations are thermally unstable and
      isomerize into the corresponding 5,10-dihydro-5,5-diphenyl-10-phenyl
      acridophosphinium (5+) and 5,10-dihydro-5,5-di(isopropyl)-10-phenyl
      acridophosphinium (6+) as tetrafluoroborate salts. These reactions suggest the
      involvement of ortho-phenylene phosphino-tritylium cations, which would be
      obtained by dissociation of the R3P+-CAr3 bonds in 4+ and 5+This article is part
      of the themed issue 'Frustrated Lewis pair chemistry'.

PMID- 28739966
TI  - Hydrogen activation using a novel tribenzyltin Lewis acid.
AB  - Over the last decade there has been an explosion in the reactivity and
      applications of frustrated Lewis pair (FLP) chemistry. Despite this, the Lewis
      acids (LAs) in these transformations are often boranes, with heavier p-block
      elements receiving surprisingly little attention. The novel LA Bn3SnOTf (1) has
      been synthesized from simple, inexpensive starting materials and has been
      spectroscopically and structurally characterized. Subtle modulation of the
      electronics at the tin centre has led to an increase in its Lewis acidity in
      comparison with previously reported R3SnOTf LAs, and has facilitated low
      temperature hydrogen activation and imine hydrogenation. Deactivation pathways of
      the R3Sn+ LA core have also been investigated.This article is part of the themed
      issue 'Frustrated Lewis pair chemistry'.

PMID- 28739967
TI  - Reactions of biologically inspired hydride sources with B(C6F5)3.
AB  - The combination of 1-benzyl-1,4-dihydropyridines with the strong Lewis acid,
      B(C6F5)3, generates a stable pyridinium borohydride species in high yields (94%)
      in as little as 10 min. This use of biologically inspired hydride sources further
      builds on the recent work of new hydride donors in the formation of borohydrides.
      When functionalizing the dihydropyridine with an amide or carboxylic acid moiety,
      a disproportionation reaction composed of a series of protonation/reduction steps
      is observed upon the addition of B(C6F5)3 As a result, one equivalent of
      dihydropyridine undergoes net hydrogenation, whereas the other is dehydrogenated
      yielding the pyridinium counterpart in a transfer hydrogenation-type
      mechanism.This article is part of the themed issue 'Frustrated Lewis pair
      chemistry'.

PMID- 28739968
TI  - Structure and reactivity of an Al/P-based frustrated Lewis pair bearing
      relatively small substituents at aluminium.
AB  - Reaction of Mes2P?C=C?Ph (Mes = mesityl) with dineopentylaluminium hydride
      afforded by hydroalumination a geminal Al/P-based frustrated Lewis pair (FLP; 4).
      Its steric shielding is relatively low, and its reactivity in various secondary
      reactions is less hindered by steric repulsion than observed for related
      compounds having bulkier groups attached to aluminium. FLP 4 yielded adducts with
      Me3C?NCO or benzaldehyde via the formation of Al-O and P-C bonds. Trimethylsilyl
      azide reacted with 4 under surprisingly mild conditions to afford a nitrene
      complex by spontaneous N2 elimination below room temperature. A carbodiimide
      molecule was coordinated via one of the C=N bonds to form a five-membered AlCPNC
      heterocycle with an intact C=N bond in an exocyclic position. A very large
      molecule was obtained by the reaction of two equivalents of 4 with a bifunctional
      methylene-bridged phenylene isocyanate precursor.This article is part of the
      themed issue 'Frustrated Lewis pair chemistry'.

PMID- 28739969
TI  - Halogenated triphenylgallium and -indium in frustrated Lewis pair activations and
      hydrogenation catalysis.
AB  - The Lewis acids Ga(C6F5)3, In(C6F5)3 and Ga(C6Cl5)3 are prepared and their Lewis
      acidity has been probed experimentally and computationally. The species Ga(C6F5)3
      and In(C6F5)3 in conjunction with phosphine donors are shown to heterolytically
      split H2 and catalyse the hydrogenation of an imine. In addition, frustrated
      Lewis pairs (FLPs) derived from Ga(C6F5)3 and In(C6F5)3 and phosphines react with
      diphenyldisulfide to phosphoniumgallates or indates of the form
      [tBu3PSPh][PhSE(C6F5)3] and [tBu3PSPh][(MU-SPh)(E(C6F5)3)2] (E = Ga, In). The
      potential of the FLPs based on Ga(C6F5)3, In(C6F5)3 and Ga(C6Cl5)3 and phosphines
      is also shown in reactions with phenylacetylene to give pure or mixtures of the
      products [tBu3PH][PhCCE(C6X5)3] and R3P(Ph)C=C(H)E(C6X5)3 A number of these
      species are crystallographically characterized. The implications for the use of
      these species in FLP chemistry are considered.This article is part of the themed
      issue 'Frustrated Lewis pair chemistry'.

PMID- 28739970
TI  - Design and reactions of a carbon Lewis base/boron Lewis acid frustrated Lewis
      pair.
AB  - The conjugated dienamine 4 selectively adds Piers' borane [HB(C6F5)2] to give the
      enamine/borane system 5, which features a boratirane structure by internal
      enamine carbon Lewis base to boron Lewis acid interaction. Compound 5 behaves as
      a C/B frustrated Lewis pair and undergoes typical addition reactions to
      benzaldehyde, several nitriles and to sulfur dioxide.This article is part of the
      themed issue 'Frustrated Lewis pair chemistry'.

PMID- 28739971
TI  - Frustrated Lewis pair chemistry.

PMID- 28739972
TI  - Recent Advances in Neurogenic Hypertension: Dietary Salt, Obesity, and
      Inflammation.

PMID- 28739974
TI  - Office Pulse Pressure Is a Predictor of Favorable Outcome in Young- to Middle
      Aged Subjects With Stage 1 Hypertension.
AB  - The role of pulse pressure in young individuals remains controversial. The aim of
      the present study was to investigate the clinical significance of elevated pulse
      pressure in young- to middle-aged subjects screened for stage 1 hypertension. We
      examined 1241 subjects (mean age, 33.1+/-8.4 years) from the HARVEST
      (Hypertension Ambulatory Recording Venetia Study), during a median follow-up of
      12.1 years. To evaluate the predictive value of pulse pressure and mean blood
      pressure for future hypertension needing treatment and for cardiovascular events,
      participants were grouped into pressure tertiles. Significant determinants of
      pulse pressure were male sex (P=0.029), younger age (P<0.001), physical activity
      (P=0.003), heart rate (P<0.001), systolic white coat effect (P<0.001), and stroke
      volume (n=829; P<0.001). During follow-up, 65.1% of participants developed
      hypertension requiring pharmacological treatment and 5.1% experienced a
      cardiovascular event. Participants in the highest pulse pressure tertile had a
      reduced risk of incident hypertension compared with those of the bottom tertile
      (hazard ratio, 0.75; 95% confidence interval, 0.62-0.91; P=0.003). In contrast,
      participants in the top mean blood pressure tertile had an increase in risk
      (1.91; 1.57-2.33; P<0.001). In addition, participants in the highest pulse
      pressure tertile had a reduced risk of cardiovascular events (0.35; 0.17-0.73;
      P=0.005) and those in the top mean blood pressure tertile had an increase in risk
      (3.06; 1.32-7.09; P=0.009). Our data show that in subjects <45 years, only mean
      blood pressure is a predictor of adverse outcome whereas high pulse pressure even
      carries a reduced risk.

PMID- 28739973
TI  - Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and
      Nitrate.
AB  - : Dietary NO3- (nitrate) and NO2- (nitrite) support .NO (nitric oxide) generation
      and downstream vascular signaling responses. These nitrogen oxides also generate
      secondary nitrosating and nitrating species that react with low molecular weight
      thiols, heme centers, proteins, and unsaturated fatty acids. To explore the
      kinetics of NO3-and NO2-metabolism and the impact of dietary lipid on nitrogen
      oxide metabolism and cardiovascular responses, the stable isotopes Na15NO3 and
      Na15NO2 were orally administered in the presence or absence of conjugated
      linoleic acid (cLA). The reduction of 15NO2- to 15NO was indicated by electron
      paramagnetic resonance spectroscopy detection of hyperfine splitting patterns
      reflecting 15NO-deoxyhemoglobin complexes. This formation of 15NO also translated
      to decreased systolic and mean arterial blood pressures and inhibition of
      platelet function. Upon concurrent administration of cLA, there was a significant
      increase in plasma cLA nitration products 9- and 12-15NO2-cLA. Coadministration
      of cLA with 15NO2- also impacted the pharmacokinetics and physiological effects
      of 15NO2-, with cLA administration suppressing plasma NO3-and NO2-levels,
      decreasing 15NO-deoxyhemoglobin formation, NO2-inhibition of platelet activation,
      and the vasodilatory actions of NO2-, while enhancing the formation of 9- and 12
      15NO2-cLA. These results indicate that the biochemical reactions and
      physiological responses to oral 15NO3-and 15NO2-are significantly impacted by
      dietary constituents, such as unsaturated lipids. This can explain the variable
      responses to NO3-and NO2-supplementation in clinical trials and reveals dietary
      strategies for promoting the generation of pleiotropic nitrogen oxide-derived
      lipid signaling mediators. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01681836.

PMID- 28739975
TI  - Complement Factor B Is a Determinant of Both Metabolic and Cardiovascular
      Features of Metabolic Syndrome.
AB  - CFB (complement factor B) is elevated in adipose tissue and serum from patients
      with type 2 diabetes mellitus and cardiovascular disease, but the causal
      relationship to disease pathogenesis is unclear. Cfb is also elevated in adipose
      tissue and serum of the spontaneously hypertensive rat, a well-characterized
      model of metabolic syndrome. To establish the role of CFB in metabolic syndrome,
      we knocked out the Cfb gene in the spontaneously hypertensive rat. Cfb-/- rats
      showed improved glucose tolerance and insulin sensitivity, redistribution of
      visceral to subcutaneous fat, increased adipocyte mitochondrial respiration, and
      marked changes in gene expression. Cfb-/- rats also had lower blood pressure,
      increased ejection fraction and fractional shortening, and reduced left
      ventricular mass. These changes in metabolism and gene expression, in adipose
      tissue and left ventricle, suggest new adipose tissue-intrinsic and blood
      pressure-independent mechanisms for insulin resistance and cardiac hypertrophy in
      the spontaneously hypertensive rat. In silico analysis of the human CFB locus
      revealed 2 cis-regulated expression quantitative trait loci for CFB expression
      significantly associated with visceral fat, circulating triglycerides and
      hypertension in genome-wide association studies. Together, these data demonstrate
      a key role for CFB in the development of spontaneously hypertensive rat metabolic
      syndrome phenotypes and of related traits in humans and indicate the potential
      for CFB as a novel target for treatment of cardiometabolic disease.

PMID- 28739978
TI  - Pressure Paradox: High Pulse Pressure and Low Mean Pressure Are Favorable
      Features in Young Adults.

PMID- 28739977
TI  - MicroRNA-210 Targets Ten-Eleven Translocation Methylcytosine Dioxygenase 1 and
      Suppresses Pregnancy-Mediated Adaptation of Large Conductance Ca2+-Activated K+
      Channel Expression and Function in Ovine Uterine Arteries.
AB  - Gestational hypoxia inhibits large conductance Ca2+-activated K+ (BKCa) channel
      expression and function in uterine arterial adaptation to pregnancy. Given the
      findings that microRNA-210 (miR-210) is increased in hypoxia during gestation and
      preeclampsia, the present study sought to investigate the role of miR-210 in the
      regulation of BKCa channel adaptation in the uterine artery. Gestational hypoxia
      significantly increased uterine vascular resistance and blood pressure in
      pregnant sheep and upregulated miR-210 in uterine arteries. MiR-210 bound to
      ovine ten-eleven translocation methylcytosine dioxygenase 1 mRNA 3' untranslated
      region and decreased ten-eleven translocation methylcytosine dioxygenase 1 mRNA
      and protein abundance in uterine arteries of pregnant sheep, as well as abrogated
      steroid hormone-induced upregulation of ten-eleven translocation methylcytosine
      dioxygenase 1 expression in uterine arteries of nonpregnant animals. In
      accordance, miR-210 blocked pregnancy- and steroid hormone-induced upregulation
      of BKCa channel beta1 subunit expression in uterine arteries. Functionally, miR
      210 suppressed BKCa channel current density in uterine arterial myocytes of
      pregnant sheep and inhibited steroid hormone-induced increases in BKCa channel
      currents in uterine arteries of nonpregnant animals. Blockade of endogenous miR
      210 inhibited hypoxia-induced suppression of BKCa channel activity. In addition,
      miR-210 decreased BKCa channel-mediated relaxations and increased pressure
      dependent myogenic tone of uterine arteries. Together, the results demonstrate
      that miR-210 plays an important role in the downregulation of ten-eleven
      translocation methylcytosine dioxygenase 1 and repression of BKCa channel
      function in uterine arteries, revealing a novel mechanism of epigenetic
      regulation in the maladaptation of uterine hemodynamics in gestational hypoxia
      and preeclampsia.

PMID- 28739979
TI  - Hypertension and VEGF (Vascular Endothelial Growth Factor) Receptor Tyrosine
      Kinase Inhibition: Effects on Renal Function.
AB  - VEGF (vascular endothelial growth factor) receptor tyrosine kinase inhibitors
      have become first-line therapy for metastatic renal cell carcinoma. Their use
      commonly leads to hypertension, but their effects on long-term renal function are
      not known. In addition, it has been suggested that the development of
      hypertension is linked to treatment efficacy. The objective of this study was to
      determine the effects of these drugs on long-term renal function, especially in
      those with renal dysfunction at baseline, and to examine the role of hypertension
      on these effects. Serum creatinine measurements were used to calculate the
      estimated glomerular filtration rate for 130 renal cell carcinoma patients who
      were treated with this class of tyrosine kinase inhibitors. New or worsening
      hypertension was defined by documented start or addition of antihypertensive
      medications. Overall, the use of tyrosine kinase inhibitors in patients with
      estimated glomerular filtration <60 or >=60 mL/min per 1.73 m2 was not associated
      with a decline in long-term renal function. During follow-up, 41 patients
      developed new or worsening hypertension within 30 days from first drug
      administration, and this was not linked to further reductions in glomerular
      filtration. These patients seemed to survive longer than those who did not
      develop hypertension within 30 days, although this was not statistically
      significant (P=0.07). Our findings suggest that the use of VEGF tyrosine kinase
      inhibitors does not adversely affect long-term renal function even in the setting
      of new-onset hypertension or reduced renal function at baseline.

PMID- 28739980
TI  - CX3CR1 modulates the anti-inflammatory activity of hepatic dendritic cells in
      response to acute liver injury.
AB  - The chemokine fractalkine (CX3CL1) and its receptor CX3CR1 are known to mediate
      leukocyte chemotaxis, adhesion and survival. In the liver, CX3CR1 is expressed on
      multiple cell types including monocytes and dendritic cells. However, the
      function of CX3CR1 on hepatic dendritic cells (HDCs) is still poorly understood.
      In this study, we investigated the role of CX3CR1 on mouse HDCs during
      homeostasis and following acute liver injury. At homeostasis, CX3CR1-expression
      was detected among CD11b+/CD103- type 2 myeloid HDCs (mHDCs) and these cells were
      characterized by the production of IL-10.   Mice treatment with the hepatotoxic
      agent CCl4 up-regulated liver IL-10 expression and stimulated the expansion of
      CX3CR1+ mHDCs which also showed a more mature phenotype. The absence of CX3CR1 in
      naive CX3CR1gfp/gfp mice specifically reduced the CD11b+/IL-10+ mHDCs as compared
      to CX3CR1-proficient animals (CX3CR1+/gfp).  Following CCl4 poisoning, the liver
      recruitment and maturation of CD11b+ mHDCs was significantly attenuated in
      CX3CR1gfp/gfp mice. Furthermore, these mice suffered more severe hepatic injury
      and inflammation than CX3CR1+/gfp mice and showed a delated recovery from liver
      damage. Such a worsening of liver injury in CX3CR1gfp/gfp mice was associated
      with an impaired up-regulation of hepatic IL-10 expression and a lower number of
      IL-10 producing CD11b+ mHDCs. Consistently, IL-10 inactivation enhanced hepatic
      injury and inflammation in CX3CR1+/gfp mice receiving CCl4 Altogether, these data
      indicate a novel role of the CX3CL1/CX3CR1 axis in liver type 2 mHDC functions,
      pointing out the importance of CX3CR1 in promoting IL-10-mediated anti
      inflammatory actions of HDCs.

PMID- 28739981
TI  - [For the Future Study on Alzheimer's Disease in Japan].

PMID- 28739982
TI  - [Preclinical AD and Biomarker; from J-ADNI to AMED Preclinical Study].
AB  - Alzheimer's disease (AD) is most prevalent cause of dementia and no cure has been
      discovered. Although the framework of AD clinical trials is being established
      utilizing results of large-scale observational studies such as the AD
      Neuroimaging Initiative (ADNI) and the Japanese-ADNI (J-ADNI), the development of
      disease-modifying therapy for Alzheimer's disease (AD) has not yet been achieved.
      Preclinical AD was recently defined as a new disease stage in which AD is
      asymptomatic but biomarkers suggest the presence of amyloid pathology.
      Preclinical AD has been focused as promising therapeutic time window and
      establishment of reliable biomarkers for preclinical AD is an urgent task. The
      Japanese Agency for Medical Research and Development (AMED) preclinical study is
      a nationwide multicenter observational study carried out by public research
      funding from AMED as a successor to the J-ADNI study. The goal of this study is
      to establish a biomarker that can quantitatively evaluate the disease progression
      of preclinical AD and mild cognitive impairment (MCI) or predict the progression
      to MCI and dementia in the future. To achieve this goal, the following
      assessments will be conducted over time for three years: clinical evaluations;
      cognitive tests; genetic testing; body fluid biomarker tests; and imaging
      biomarker studies such as MRI, FDG-PET, and amyloid PET. The obtained data will
      eventually be released to the public database.

PMID- 28739983
TI  - [DIAN/DIAN-J/DIAN-TU].
AB  - The Dominantly Inherited Alzheimer's Network (DIAN) observational study compared
      pathophysiological markers between mutation carriers and non-carriers in
      autosomal dominant Alzheimer's disease. This study revealed that changes in the
      biomarkers in the mutation carrier's brain start as early as 20 or even 25 years
      prior to the onset of symptoms. Doctors of the DIAN-Japan team have successfully
      implemented the DIAN study in Japan (DIAN-J) with effort and enthusiasm. The DIAN
      J study is completely compatible with the DIAN study. All members of the DIAN-J
      team were certified by the NIH and Washington University. The DIAN researchers
      started a prevention trial (DIAN-TU) testing two monoclonal antibodies in 2013.
      Together with the DIAN global members including the Japanese team, they will
      start the new DIAN-TU NexGen Trial testing a BACE inhibitor in 2017. The API
      study is another clinical trial of anti-amyloid monoclonal antibody therapy for
      family members of patients with early-onset familial AD who carry the PSEN1 E280A
      mutation. This study has shown the same biomarker changes that were reported in
      the DIAN study.

PMID- 28739984
TI  - [Toward Preclinical Trials for Alzheimer's Disease].
AB  - A variety of disease-modifying therapies for Alzheimer's disease (AD) have been
      developed and advanced to late-phase clinical trials in AD dementia patients, but
      thus far, no single drug has proven its efficacy in a large phase III trial. In
      2011, the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria
      redefined the concept of AD to encompass the earlier amyloid-related
      pathophysiological changes of the preclinical stage and mild cognitive impairment
      (MCI). Clinical trials for AD are now moving toward these earlier stages of the
      disease, targeting MCI due to AD and preclinical AD. Intervention in the earlier
      stages of the amyloid cascade is believed to have a better chance at changing the
      natural course of AD and preventing or at least delaying the conversion to
      dementia. Although conducting a large and prolonged costly clinical trial in the
      preclinical stage is challenging, the first step in overcoming this challenge has
      been taken with enthusiasm and commitment.

PMID- 28739985
TI  - [A Review of Clinical Studies Investigating Patients with Alzheimer's Disease
      having Genetic Risk Factors].
AB  - Aside from the current conventional pharmaceutical therapies that have limited
      effects on patients with Alzheimer's disease, disease-modifying therapies have
      been developed to inhibit the pathological processes of Alzheimer's disease.
      These include immunotherapies, beta/gamma secretase inhibitors, and aggregation
      inhibitors targeting amyloid beta. The involvement of genetic risk factors in the
      effectiveness of such processes has been confirmed. For example, apolipoprotein E
      epsilon4 carriers have been reported to have a risk of ARIA (Amyloid Related
      Imaging Abnormality) as an adverse effect by those therapies. In this paper, we
      review clinical studies examining patients with Alzheimer's disease, having
      genetic risk factors.

PMID- 28739986
TI  - [Support Team for Investigator-Initiated Clinical Research].
AB  - Investigator-initiated clinical research is that in which investigators plan and
      carry out their own clinical research in academia. For large-scale clinical
      research, a team should be organized and implemented. This team should include
      investigators and supporting staff, who will promote smooth research performance
      by fulfilling their respective roles. The supporting staff should include project
      managers, administrative personnel, billing personnel, data managers, and
      clinical research coordinators. In this article, I will present the current
      status of clinical research support and introduce the research organization of
      the Dominantly Inherited Alzheimer Network (DIAN) study, an investigator
      initiated international clinical research study, with particular emphasis on the
      role of the project management staff and clinical research coordinators.

PMID- 28739987
TI  - [Registries to Boost the Clinical Trials for the Disease Modifying Therapy of
      Alzheimer's Disease].
AB  - The development of disease-modifying therapies (DMT) for Alzheimer's disease (AD)
      is an urgent goal worldwide. Since the first clinical trial of Abeta immunization
      therapy in 2001, a number of trials targeting early-stage AD dementia have
      failed. Researchers now believe that DMT must be initiated much earlier than in
      these failed trials, i.e., at the preclinical or prodromal stages of AD. This
      notion is supported by AD biomarker studies, which have revealed that Abeta and
      tau accumulation appears 10 to 30 years prior to the occurrence of dementia and
      propagates gradually in the brain to a symptomatic level. However, clinical
      trials that involve people without dementia have a number of difficulties in the
      recruitment of participants. The trial sites are required to perform outreach
      procedures to find potential participants. The AD biomarker tests are either
      costly or invasive, and the rate of biomarker-positive subjects in the non
      demented population is low, suggesting a high screening failure rate. Preclinical
      AD registries are a possible solution to overcome such difficulties. These
      registries pool non-demented individuals who are interested in AD clinical
      research and collect information on demographics and the presence or absence of
      genetic, lifestyle, and other risk factors. A number of these registries have
      been established in the United States. An internet-based registry, IROOP, was
      launched in Japan in 2016.

PMID- 28739988
TI  - [Orange Platform].
AB  - The Organized Registration for the Assessment of dementia on Nationwide General
      consortium toward Effective treatment in Japan (ORANGE platform) is a recently
      established nationwide clinical registry for dementia. This platform consists of
      multiple registries of patients with dementia stratified by the following
      clinical stages: preclinical, mild cognitive impairment, early-stage, and
      advanced-stage dementia. Patients will be examined in a super-longitudinal
      fashion, and their lifestyle, social background, genetic risk factors, and
      required care process will be assessed. This project is also notable because the
      care registry includes information on the successful, comprehensive management of
      patients with dementia. Therefore, this multicenter prospective cohort study will
      contribute participants to all clinical trials for Alzheimer's disease as well as
      improve the understanding of individuals with dementia.

PMID- 28739989
TI  - [The Need for a Trial Ready Cohort of Preclinical Alzheimer's Disease].
AB  - In order to slow the predicted increase in the number of individuals with
      dementia, disease-modifying drugs for Alzheimer's disease (AD) are under
      development. Early-stage intervention is thought to be required for AD, since
      this disease involves a very long pathological process that leads to dementia in
      the final stage, when disease-modifying drugs have little effect. To justify this
      early intervention, we establish the concept of preclinical AD, when AD pathology
      is already present prior to the onset of cognitive decline. Since individuals
      with preclinical AD have no symptoms, we need to establish an effective way to
      recruit them to clinical trials.

PMID- 28739990
TI  - [Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD)].
AB  - Dementia has become a priority worldwide in terms of both public health and
      social care due to its rapidly increasing burden in communities. Therefore, the
      early identification of possible risk factors and the establishment of preventive
      and treatment strategies for dementia have become increasingly important. The
      Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a
      collaborative prospective cohort study of approximately 10,000 elderly people
      from 8 newly established community-based dementia cohort studies in Japan. In
      this study, the data are prospectively collected using a pre-specified
      standardized protocol. The purpose of this study is to quantitatively evaluate
      the environmental and genomic risk factors for dementia in Japan and to establish
      effective preventive strategies to promote a healthy aging society.

PMID- 28739991
TI  - [The Prevalence and Risk Factors of Dementia in Centenarians].
AB  - Centenarians are less susceptible to the diseases, functional losses and
      dependencies related to old age than the general public, and are therefore
      regarded as model cases of successful aging. For this reason, an important focus
      of the study of centenarians is their relative resilience to age-related
      cognitive decline or dementia. In the Tokyo Centenarian Study, we found
      approximately 60% of centenarians to have dementia; however, supercentenarians
      (those people living at least 110 years) maintained normal cognitive function at
      100 years of age. Our preliminary data also demonstrated extremely low
      frequencies of the apolipoprotein E4 allele in supercentenarians. Moreover,
      postmortem brain samples from supercentenarians demonstrated relatively mild age
      related neuropathological findings. Therefore, a more extensive investigation of
      supercentenarian populations might provide insight into successful brain aging.

PMID- 28739992
TI  - [Current Clinical Assessment Scales and Cognitive Tests in Global Clinical
      Studies on Alzheimer's Disease].
AB  - To quantify the severity of clinical symptoms and cognitive dysfunction, clinical
      assessment scales and cognitive tests are used in clinical studies involving
      patients with Alzheimer's disease (AD). As an increasing number of clinical
      studies involving individuals with preclinical AD and mild cognitive impairment
      are being conducted, newly developed scales are also utilized in those studies.
      Scales and tests must be translated into Japanese and validated, with the level
      of difficulty kept equal to the original, in order to obtain data comparable to
      those of other countries, in global studies. Moreover, the uniformity of
      procedures in test administration is crucial to procuring high-quality data in
      multicenter clinical studies. Such background efforts, which support novel
      scientific findings, as well as clinical assessment scales and cognitive tests
      which are used in recent studies are described in this section.

PMID- 28739993
TI  - [Emerging Therapeutic Targets Revealed by Genome Analysis in Alzheimer's
      Disease].
AB  - Cutting-edge genomics technologies have substantially improved our understanding
      of the pathogenesis of Alzheimer's disease (AD). The identification of mutations
      in APP, PSEN1, and PSEN2 causative for autosomal dominant AD (ADAD) has provided
      the basis of the "amyloid cascade" hypothesis of the pathogenetic mechanism of
      AD. While a number of therapeutic candidates targeting amyloid-beta were
      developed using genetically engineered mouse models of ADAD, none have proven
      successful in mitigating the symptoms of AD in phase III clinical trials. Thus,
      we must reconsider the modification of AD pathogenesis by targets within the
      amyloid cascade, and explore new targets for AD therapy. This review provides a
      comprehensive summary of the recent genetic studies of AD from this perspective,
      and discusses prospective and emerging therapeutic interventions for patients
      with AD.

PMID- 28739994
TI  - [The Application of Magnetic Resonance Imaging in Alzheimer's Disease].
AB  - In Alzheimer's disease (AD), magnetic resonance imaging (MRI) is essential for
      early diagnosis, differential diagnosis, and evaluation of disease progression.
      In structural MRI, the automatic diagnosis of atrophy by computers, even when it
      is not visually noticeable, is possible in daily clinical practice. Furthermore,
      subfield volumetric measurements of the medial temporal structures, as well as
      longitudinal volume measurements with high accuracy, have been developed and are
      useful for calculating the needed sample size in clinical trials. In addition to
      detecting local atrophy, graph theory has been applied to structural MRI for
      evaluation of alterations of the brain networks potentially affected in AD.

PMID- 28739995
TI  - [Amyloid Positron Emission Tomography in the Therapeutic Strategies for
      Alzheimer's Disease].
AB  - Amyloid positron emission tomography (PET) has been developed as a non-invasive
      neuroimaging technique that enables us to visualize the accumulation of fibrillar
      amyloid-beta (Abeta) in the living human brain with histopathological
      confirmation. As the deposition of fibrillar Abeta is the earliest detectable
      biomarker of Alzheimer's disease (AD), amyloid PET is useful not only to increase
      the probability of a correct diagnostic in clinical practice and clinical
      studies, but also to enrich appropriate participants in the clinical trials of
      disease modifying drugs for early stage of AD. The amyloid positivity has been
      shown to be affected by age and APOE epsilon4 allele presence. In combination
      with the emerging technique of tau imaging, amyloid PET will reveal details of
      the early pathophysiological mechanism of AD, which will lead to the development
      of effective disease modifying therapies and prevention strategies. Amyloid
      negativity by amyloid PET is the most reliable marker to exclude the possibility
      of AD in the differential diagnosis of dementia diseases. Therefore, amyloid
      imaging is also essential for the clinical studies and clinical trials targeting
      non-AD dementia diseases such as frontotemporal lobar degeneration, argyrophilic
      grain disease and neurofibrillary tangle dominant disease. Establishing an in
      vivo imaging technique to visualize tau and alpha synuclein will accelerate
      further understanding of non-AD dementias.

PMID- 28739996
TI  - [Tau Positron Emission Tomography].
AB  - Accumulation of fibrillar tau protein aggregates is a neuropathological hallmark
      of Alzheimer's disease (AD) and related neurodegenerative dementias, including a
      subgroup of frontotemporal lobar degeneration (FTLD). Visualization of tau
      lesions in the brains of living subjects enables a pathology-based diagnosis of
      dementing illnesses in the prodromal stage, and offers objective measures of
      disease progression and outcomes of disease-modifying therapies. With this
      rationale, diverse classes of low-molecular-weight chemicals capable of binding
      to a beta-pleated sheet structure have been developed to be used for in vivo
      positron emission tomography (PET) of tau pathologies. Clinical PET studies of AD
      patients with such tau probes have provided the following insights: (1) Tau
      fibrils accumulate in the hippocampal formation in an age-dependent manner that
      is independent of amyloid-beta peptide (Abeta) pathology; (2) The deposition of
      Abeta may trigger a spatial expansion of tau pathology, in transition from normal
      aging to advanced AD; and (3) Tau accumulation is intimately associated with
      local neuronal loss, leading to cortical atrophy and focal symptoms. In contrast,
      studies of FTLD have shown a limited performance of first-generation PET probes
      in capturing non-AD-type tau lesions. New compounds have accordingly been
      developed and clinically tested, proving to yield a high contrast for tau
      deposits with high specificity. These second-generation probes are being
      evaluated primarily by pharmaceutical companies, in line with their growing
      demands for neuroimaging-based biomarkers serving for clinical trials of anti
      Abeta and anti-tau therapies. Meanwhile, a consortium flexibly linking academia
      and industry to facilitate the utilization of research tools, including tau PET
      probes, has been established in Japan, for the ultimate purpose of elucidating
      the molecular etiology of tauopathies and creating diagnostic and therapeutic
      agents based on such an understanding.

PMID- 28739997
TI  - [Cerebrospinal Fluid and Blood Biomarkers in Alzheimer's Disease].
AB  - To cope with an aging society, development of disease-modifying drugs for
      Alzheimer's disease (AD) is essential. Currently, only symptomatic treatments
      that suppress clinical manifestations are available. Amyloid-beta<sub>42</sub>
      (Abeta<sub>42</sub>) is an AD-related pathogenic molecule that triggers
      development of AD pathology; thus, decreasing Abeta<sub>42</sub> in the brain is
      a promising candidate for AD therapy. Numerous pharmaceutical companies have
      developed therapeutic drugs against Abeta<sub>42</sub>, such as beta-secretase
      inhibitors, gamma-secretase inhibitors, and anti-Abeta monoclonal antibodies, but
      in clinical trials for patients with mild to moderate AD, these drugs did not
      meet the expected endpoints. These results suggest that earlier administration of
      these drugs to individuals who have not yet developed cognitive decline, but have
      AD pathological changes in the brain or high risk of developing these changes,
      may be beneficial. To enable such early treatment, preclinical AD biomarkers are
      required. In this review, we comment on current AD biomarkers in cerebrospinal
      fluid and in blood. We also explain CSF/blood APL1beta, which is a candidate
      surrogate marker for Abeta<sub>42</sub> in the brain.

PMID- 28739998
TI  - [Bioinformatics Analysis of Alzheimer's Disease].
AB  - With the spread of microarray and next-generation sequencing technologies,
      massive amounts of data can be collected. However, these collections of data
      require the use of "big data" data-mining techniques to extract the relevant
      information. These techniques are applied to biological data through
      bioinformatics studies. By applying these bioinformatics approaches to various
      omics datasets, the complex pathology of Alzheimer's disease (AD) has been
      substantially revealed. In this paper, we focus on the genomics- and
      transcriptomics-based studies, and review previous AD studies using these newer
      bioinformatics approaches.

PMID- 28739999
TI  - [Clinical Research and Biostatistics].
AB  - We discuss the important role of biostatisticians in clinical research. In
      addition, the biases that occur in a study, especially "confounding" in an
      observational study, are discussed using a real example. Finally, the manuscript
      provides an overview of propensity score matching, a method to eliminate
      confounding.

PMID- 28740000
TI  - [Introduction to Research Electronic Data Capture (REDCap) and REDCap2SDTM, a
      Conversion Tool to Facilitate Clinical Research Data Sharing].
AB  - Clinical Data Interchange Standards Consortium (CDISC), Study Data Tabulation
      Model (SDTM) is used in new drug application studies and for sharing and reuse of
      accumulated clinical research data. Clinical trial manuscripts submitted to
      International Committee of Medical Journal Editors member journals are required
      to contain a statement on data sharing. We introduce here Research Electronic
      Data Capture (REDCap) and REDCap2SDTM, a tool for converting research data to
      CDISC SDTM for facilitating data sharing. This tool will help reduce the workload
      in new drug application studies and allow the effective reuse of clinical
      research data.

PMID- 28740001
TI  - [Alzheimer's Therapeutic Research Institute].
AB  - The Alzheimer's Therapeutic Research Institute (ATRI) was established in 2015
      after ATRI director, Paul Aisen, and his fellow experts in therapeutic
      interventions for Alzheimer's disease (AD) moved from the Alzheimer's Disease
      Cooperative Study (ADCS) at the University of California to the Keck School of
      Medicine of the University of Southern California. The National Institute on
      Aging (NIA) decided to commit $14 million to the ATRI via an Alzheimer's Clinical
      Trials Consortium (ACTC). The ATRI supports various studies such as the Anti
      Amyloid Treatment in Asymptomatic Alzheimer's study ("A4 study"), Alzheimer's
      Disease Neuroimaging Initiative 3 (ADNI3), Longitudinal Evaluation of Amyloid
      Risk and Neurodegeneration (LEARN), and The Alzheimer's Disease Neuroimaging
      Initiative-Depression Project (ADNI-D). The ATRI will share all relevant data and
      materials with the academic community, corporations, and government
      organizations. The ATRI is overseen by a Data and Safety Monitoring Board (DSMB),
      which comprises of leading experts in the field of Alzheimer's research and acts
      independently. The ATRI is slated to play a central role in clinical dementia
      research in the US in near future.

PMID- 28740002
TI  - [A Case of Amusia Following Right Temporal Subcortical Hemorrhage].
AB  - A woman in her 60s presented with amusia due to a localized subcortical
      hemorrhage of the right temporal lobe. No other symptoms of higher brain
      dysfunction or body paralysis were observed. One characteristic symptom in this
      case was rhythm impairment. Few cases of this impairment have been previously
      reported, and the responsible lesion and underlying mechanisms are still a matter
      of speculation. However, in this case, a relationship with the right temporal
      lobe was indicated.

PMID- 28740025
TI  - Superior heterojunction properties of solution processed copper-zinc-tin-sulphide
      quantum dots on Si.
AB  - CZTS nanocrystals have been synthesized via a new facile and environmentally
      friendly route using olive oil at a relatively low temperature. Nanocrystals
      synthesized using olive oil have a smaller average size in comparison to those
      synthesized with a conventional solvent-like ethylenediamine. Nanocrystals with
      an average diameter of 40, 20 and 6 nm have been extracted from the olive oil at
      different centrifugation speeds of 500, 1000 and 2000 rpm, respectively. The
      photovoltaic characteristics of p-CZTS/n-Si heterojunctions fabricated using the
      synthesized colloidal quaternary nanocrystals are demonstrated. The device
      fabricated with smallest sized CZTS nanocrystals, having an average diameter of
      ~6 nm, exhibits an enhancement in power conversion efficiency of 61% in
      comparison to that of the device fabricated with the nanocrystals of 40 nm in
      diameter. A lower reflectance and higher minority carrier life time along with a
      larger surface-to-volume ratio resulted in an enhanced power conversion
      efficiency for smaller sized CZTS nanocrystals.

PMID- 28740026
TI  - 5,6-Dihydropyrrolo[2,1-a]isoquinolines as Alternative of New Drugs with Cytotoxic
      Activity.
AB  - In this study, the pyrrolo[2,1-a]isoquinolines 4a-n were synthesized in good
      yields in a three steps synthesis from the corresponding alpha,beta-unsaturated
      esters starting materials. These compounds were tested on six human cancer cells
      lines to measure the cytotoxic activity as a function of the electronic
      properties and aromaticity of the substituent at the C-2 position of the
      pyrroloisoquinoline. Our results reveal that the cytotoxic activity could be
      explained in terms of the distribution of electronic density across the ring
      joined to C-2. Also, this study identified 3-hydroxy (4d) and 3-chloro (4j)
      derivatives with powerful cytotoxic activities. The IC50 values of these
      compounds were found to be comparable to those of the commercially available
      Topotecan, Irinotecan, Etoposide, Tamoxifen, and Cisplatin.

PMID- 28740027
TI  - Heart failure and sleep disordered breathing.
AB  - Sleep-disordered breathing (SDB) is frequently observed in patients with heart
      failure (HF), and complex pathologic conditions exist between both conditions. In
      this review article, we describe the characteristics of SDB complicated with HF,
      the prognostic impact of SDB in HF patients, and the favorable effects of
      positive airway pressure in HF patients with SDB.

PMID- 28740028
TI  - 10-Hydroxy-2-decenoic acid, a natural product, improves hyperglycemia and insulin
      resistance in obese/diabetic KK-Ay mice, but does not prevent obesity.
AB  - 10-Hydroxy-2-decenoic acid (10H2DA) is a fatty acid found in royal jelly (RJ). In
      healthy mice, it activates 5'-AMP-activated protein kinase (AMPK) and increases
      glucose transporter 4 (GLUT4) translocation. Therefore, we examined whether
      10H2DA has a potential therapeutic effect against type 2 diabetes in
      obese/diabetic KK-Ay mice. 10H2DA (3 mg/kg body weight) was administered to
      female KK-Ay mice for 4 weeks by oral gavage. Phenotypes for body weight, plasma
      glucose by oral glucose tolerance test and insulin levels were measured. mRNA and
      protein levels were determined using qRT-PCR and Western blot analyses,
      respectively. Long-term administration of 10H2DA significantly improved
      hyperglycemia and insulin resistance in KK-Ay mice, but did not prevent obesity.
      10H2DA increased the expression of phosphorylated AMPK (pAMPK) protein in
      skeletal muscles; however, this expression did not correlate with increased GLUT4
      translocation. Furthermore, 10H2DA neither enhanced the expression of adiponectin
      receptor mRNA nor activated the insulin signaling cascade, such as GSK-3beta
      phosphorylation, in the liver. We found that 10H2DA-treated mice had a
      significant increase in the expression of peroxisome proliferator-activated
      receptor gamma coactivator 1 alpha (Pgc-1alpha) mRNA in skeletal muscles compared
      with non-treated group (P=0.0024). These findings suggest that 10H2DA is involved
      in the improvement of type 2 diabetes, at least in part via activation of Pgc
      1alpha expression, but does not prevent obesity.

PMID- 28740030
TI  - Phylogenetic Characteristics of Mycobacterium tuberculosis Clinical Isolates in
      Akita Prefecture, Japan, on the Basis of the Preliminary Detection of Beijing
      Family Strains.

PMID- 28740029
TI  - Promoting physical activity in the workplace: A systematic meta-review.
AB  - INTRODUCTION: Physically active (PA) people have a lower risk of various
      diseases, compared to those with sedentary lifestyles. Evidence on the effects of
      PA promoting programs in the workplace is large, and several systematic reviews
      (SR) and/or meta-analyses (MA) have been published. However, they have failed to
      consider factors that could influence interventions. This paper aimed to classify
      and describe interventions to promote PA in the workplace based on evidence from
      SR/MA. METHOD: A literature search for SR/MA was done using PubMed, Web of
      Science, and Science Direct (January 2006-February 2015). Quality assessment of
      SR/MA was performed using AMSTAR. The PRECEDE-PROCEED model was used for
      classifying the interventions into predisposing, enabling, reinforcing,
      environment, and policy domains of focus. RESULTS: Eleven SR/MA included 220
      primary studies, of which 139 (63%) were randomized controlled trials. Of 48
      interventions identified, 22 (46%) and 17 (35%) focused on predisposing or
      enabling employees to have more PA, respectively. Of the 22 predisposing factors,
      6 were information delivery, 5 were self-motivation, and 11 were program
      training. The enabling approaches were 12 instrument resources and 5 health
      service facilities. The reinforcing approaches were 4 incentive and 3 social
      support. The remaining interventions focused on the environmental development and
      policy regulation. CONCLUSIONS: This systematic meta-review classified
      interventions using appropriate framework and described the intervention pattern.

PMID- 28740031
TI  - Age-Specific Determinants of Pulse Wave Velocity among Metabolic Syndrome
      Components, Inflammatory Markers, and Oxidative Stress.
AB  - AIM: Pulse wave velocity (PWV) is thought to have different relationships with
      metabolic syndrome (MS) components, inflammatory markers, and oxidative stress,
      according to age. However, age-specific determinants of PWV have not yet been
      studied. We investigated age-dependent relationships among PWV and MS components,
      inflammatory markers, and oxidative stress. METHODS: A total of 4,318 subjects
      were divided into 4 groups: 19-34 y (n=687), 35-44 y (n=1,413), 45-54 y
      (n=1,384), and 55-79 y (n=834). MS components, brachial-ankle PWV (baPWV), high
      sensitivity C-reactive protein (hs-CRP), and oxidative stress markers were
      measured. RESULTS: There were age-related increases in MS, body mass index (BMI),
      waist circumference, systolic blood pressure (SBP), diastolic BP (DBP),
      triglycerides, glucose, hs-CRP, oxidized low-density lipoprotein (LDL), 8-epi
      prostaglandin F2alpha (8-epi-PGF2alpha), and baPWV. BaPWV was significantly
      associated with sex and elevated BP in the 19-34 y group; with age, sex, BMI,
      elevated BP and triglycerides in the 35-44 y group; with age, sex, elevated BP,
      fasting glucose, hs-CRP and oxidized LDL in the 45-54 y group; and with age, BMI,
      elevated BP, fasting glucose and oxidized LDL in the 55-79 y group. CONCLUSIONS:
      Our results show that age-related increases in baPWV are associated with age
      related changes in MS components, inflammatory markers, and oxidative stress.
      However, each of these factors has an age-specific, different impact on arterial
      stiffness. In particular, oxidative stress may be independently associated with
      arterial stiffness in individuals older than 45 y.

PMID- 28740032
TI  - Effect of diagnosis and treatment of clinical endometritis based on vaginal
      discharge score grading system in postpartum Holstein cows.
AB  - In this study, the prevalence, effectiveness of diagnosis, and treatment based on
      vaginal discharge score (VDS) of clinical endometritis in cattle were evaluated.
      To detect clinical endometritis and classify its severity, vaginoscopy was
      performed during 21 to 60 days postpartum in 164 Holstein cows consisting of 229
      lactations. Groups were defined using the 4-point VDS scale. Study groups
      included the following: non-endometritis (VDS=0; no/clear mucus; NEM group;
      n=168); mild endometritis, no treatment (VDS=1; mucus containing flecks of
      white/off-white pus; NTR group; n=30); and severe endometritis, treated with
      PGF2alpha (VDS>=2; discharge containing <50% pus; and VDS=3; discharge containing
      >50% pus, and fluid or uterine horn asymmetry; TEM group; n=31). Cows treated
      with PGF2alpha that did not recover (VDS>=1, n=5) received intrauterine procaine
      penicillin and streptomycin. Prevalence of clinical endometritis (VDS>=1) was
      26.6%. The NTR group required significantly more artificial inseminations per
      pregnancy than NEM and TEM groups (2.8 +/- 1.8 vs 2.0 +/- 1.3, 1.9 +/- 0.8,
      P<0.05). In survival analysis, the proportion of non-pregnant cows was higher in
      the NTR group compared to the NEM (P=0.012) and TEM (P=0.076) groups. In the TEM
      group, calving to first artificial insemination interval tended to be higher in
      cows treated 41 to 60 days postpartum than cows treated 29 to 40 days postpartum
      (97.2 +/- 27.1 vs 74.4 +/- 19.7, P=0.084). Our study suggests that cows with
      VDS=1 may require treatment to recover fertility. Diagnosis and treatment of
      clinical endometritis based on a VDS grading system may improve dairy herd
      reproductive performance.

PMID- 28740033
TI  - Disseminated histiocytic sarcoma with hemophagocytosis in a rabbit.
AB  - A 7-year-old female domestic rabbit suffered from labored respiration, poor
      appetite, mild anemia and thrombocytopenia. Radioscopic examination revealed
      masses in multiple locations including the intrapleural cavity and spleen. Forty
      three days after the first visit to a private veterinary clinic, the rabbit died
      of severe respiratory distress. Microscopically, all of the masses were composed
      of round to polygonal neoplastic cells with distinct cell borders that were
      arranged in a sheet pattern. Multinucleated giant neoplastic cells were often
      observed. Some neoplastic cells had phagocytozed one or more erythrocytes.
      Immunohistochemical staining revealed that the neoplastic cells expressed
      vimentin, CD204, Iba-1 and lysozyme, but not CD163. Based on the morphological
      and immunohistochemical findings, this case was diagnosed as disseminated
      histiocytic sarcoma with hemophagocytosis.

PMID- 28740034
TI  - The impact of meal timing on performance, sleepiness, gastric upset, and hunger
      during simulated night shift.
AB  - This study examined the impact of eating during simulated night shift on
      performance and subjective complaints. Subjects were randomized to eating at
      night (n=5; 23.2 +/- 5.5 y) or not eating at night (n=5; 26.2 +/- 6.4 y). All
      participants were given one sleep opportunity of 8 h (22:00 h-06:00 h) before
      transitioning to the night shift protocol. During the four days of simulated
      night shift participants were awake from 16:00 h-10:00 h with a daytime sleep of
      6 h (10:00 h-16:00 h). In the simulated night shift protocol, meals were provided
      at ~0700 h, 1900 h and 0130 h (eating at night); or ~0700 h, 0930 h, 1410 h and
      1900 h (not eating at night). Subjects completed sleepiness, hunger and gastric
      complaint scales, a Digit Symbol Substitution Task and a 10-min Psychomotor
      Vigilance Task. Increased sleepiness and performance impairment was evident in
      both conditions at 0400 h (p<0.05). Performance impairment at 0400 h was
      exacerbated when eating at night. Not eating at night was associated with
      elevated hunger and a small but significant elevation in stomach upset across the
      night (p<0.026). Eating at night was associated with elevated bloating on night
      one, which decreased across the protocol. Restricting food intake may limit
      performance impairments at night. Dietary recommendations to improve night-shift
      performance must also consider worker comfort.

PMID- 28740035
TI  - Six-Month Lower Limb Aerobic Exercise Improves Physical Function in Young-Old,
      Old-Old, and Oldest-Old Adults.
AB  - The effect of aerobic exercise on physical function and mental health in various
      adult age groups (young-old, 65-74; old-old, 75-84; oldest-old, >= 85 years) is
      unclear. The aim of this study was to investigate the effects of the Kohzuki
      Exercise Program (KEP) on physical function and mental health in these age
      groups. The KEP consisted of 40-min supervised sessions 3 times per week for 6
      months as follows: 5 min of warm-up, 30 min of lower limb aerobic exercise, and 5
      min of cool-down. A total of 50 participants (22 young-old, 20 old-old, and 8
      oldest-old) who participated in the KEP completed at least 88% of the sessions.
      In statistical analysis, 3 (group: oldest-old, old-old, young-old) * 2 (time:
      baseline and after 6 months) analyses of variance were used to determine if there
      were significant main and interaction effects. Significant interactions were
      probed using the post-hoc paired t test. The Short Physical Performance Battery
      (SPPB) score showed significant group * time interactions after 6 months (p =
      0.031). In the post-hoc test, oldest-old (p < 0.001), old-old (p < 0.001), and
      young-old (p < 0.01) groups had significantly better physical function after 6
      months. However, none of the mental health measures showed group * time
      interactions at 6-month. Our results suggest that a 6-month KEP led to improved
      physical function in oldest-old, old-old, and young-old adults. The KEP was
      effective for oldest-old adults in particular. The KEP exhibits good adherence,
      making it suitable for a wide age range in society.

PMID- 28740036
TI  - Increased Serum 25(OH)D3 Levels in Post-Menopausal Japanese Women with
      Osteoporosis after 3-Year Bisphosphonate Treatment.
AB  - Osteoporosis is characterized by the systemic impairment of bone mass, strength,
      and microarchitecture, leading to an increased risk of fragility fracture.
      Bisphosphonates (BPs) are the first-line drugs for osteoporosis. Vitamin D is
      considered to be essential for osteoporotic treatment. However, long-term effects
      of BPs on the serum levels of 25-hydroxyvitamin D3 (25(OH)D3) are unknown.
      Accordingly, in this retrospective study, we collected clinical data of 41 post
      menopausal Japanese women with osteoporosis treated with BP for over 3 years,
      without vitamin D supplementation. We measured lumbar and femoral neck bone
      mineral density (BMD) and serum levels of bone specific alkaline phosphatase
      (BAP) as a bone formation marker, and tartrate-resistant acid phosphatase (TRACP)
      5b as a bone resorption marker, before and after the 3-year treatment. Serum
      25(OH)D3, 1,25(OH)2D3, and whole parathyroid hormone (PTH) were also measured.
      Notably, no fracture occurred during the treatment. Compared with baseline
      values, 25(OH)D3 levels were significantly increased from 21.6 to 26.4 ng/mL (P =
      0.006), despite no vitamin D supplementation. 1,25(OH)2D3 and whole PTH levels
      tended to be decreased from 62.6 to 57.8 pg/mL and 27.3 to 25.1 pg/mL,
      respectively. Both bone formation and resorption markers were significantly
      suppressed (P < 0.01). Both lumbar BMD (7.3% increase) and femoral neck BMD (4.1%
      increase) were significantly improved (P < 0.0001) after 3 years of the
      treatment. Thus, even without vitamin D supplementation, serum 25(OH)D3 levels
      were significantly increased after 3-year BP therapy. These results suggest that
      vitamin D supplementation might not be required in the long-term BP therapy for
      osteoporosis.

PMID- 28740037
TI  - A Victim of the Great East Japan Earthquake Identified with the Preserved Medical
      Samples of Her Deceased Mother.
AB  - On March 11, 2011, a magnitude 9.0 earthquake and huge tsunami occurred near the
      Pacific coast of northeast Japan, in which more than 18,000 people died or went
      missing and more than 120,000 buildings were destroyed. In Taro district, one of
      the areas struck hardest by the tsunami, a middle-aged woman was found deceased
      in the rubble. Generally, a family physician can recognize victims based on their
      appearance; the place where they were found; their home or work address; their
      belongings; the identifying marks on their clothes; their dental charts; and
      their living biological parents, children, or multiple siblings through DNA
      analysis. However, in this case, the middle-aged woman remained the area's sole
      unidentified person for months, because her appearance was different, her body
      was slightly swollen, and she was missing some teeth. The district's medical and
      dental facilities were destroyed and almost all medical records and dental charts
      lost. Fortunately, a family physician who had worked in the district for many
      years survived the disaster, and was available to provide background information
      about the victim, her family, and their relationship. He recalled the existence
      of tissue samples of her mother who had died several years earlier. Subsequently,
      the individual was identified through the DNA analysis of her blood and mother's
      tissue samples. As demonstrated in the case, appropriately managed medical
      information and samples from previously deceased relatives can aid disaster
      victim identification. The destruction caused by the Great East Japan Earthquake
      forms our investigation's background.

PMID- 28740038
TI  - Identification of Left Atrial Appendage Thrombi in Patients With Persistent and
      Long-Standing Persistent Atrial Fibrillation Using Intra-Cardiac Echocardiography
      and Cardiac Computed Tomography.
AB  - BACKGROUND: Intracardiac echocardiography (ICE) and cardiac computed tomography
      (CCT), in addition to standard transesophageal echocardiography (TEE), have been
      used to identify left atrial (LA) thrombi prior to ablation for atrial
      fibrillation (AF). The clinical advantages of this, however, remain unclear. This
      study therefore investigated the advantages of additional pre-procedural LA
      appendage (LAA) thrombus evaluation using ICE and the clinical value of CCT in
      persistent and long-standing persistent AF.Methods and Results:We analyzed data
      from 108 consecutive patients with persistent and long-standing persistent AF who
      were scheduled to undergo AF ablation. TEE was performed within 24 h prior to
      ablation. ICE was performed for 97 patients in whom a thrombus was not detected
      on TEE. CCT was performed in 95 patients. Thrombus or sludge was detected on TEE
      in 11 patients (10.3%), for whom ablation was cancelled. Four additional patients
      were diagnosed with LAA thrombus on ICE. When TEE and ICE were used as the
      reference for thrombus detection, the sensitivity, specificity, positive
      predictive value, and negative predictive value of CCT for identifying contrast
      defects in the LAA were 100%, 81.0%, 40.7%, and 100%, respectively. CONCLUSIONS:
      ICE combined with TEE increased the detection rate of LAA thrombi in patients
      with persistent and long-standing persistent AF. Moreover, CCT had high
      sensitivity and negative predictive value for LAA thrombus detection.

PMID- 28739976
TI  - Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study
      and Expression Data Sets From Blood and the Kidney.
AB  - Elevated blood pressure is a major risk factor for cardiovascular disease and has
      a substantial genetic contribution. Genetic variation influencing blood pressure
      has the potential to identify new pharmacological targets for the treatment of
      hypertension. To discover additional novel blood pressure loci, we used 1000
      Genomes Project-based imputation in 150 134 European ancestry individuals and
      sought significant evidence for independent replication in a further 228 245
      individuals. We report 6 new signals of association in or near HSPB7, TNXB,
      LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a
      further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression
      resources totaling 12 607 individuals, we investigated all novel and previously
      reported signals and identified 48 genes with evidence for involvement in blood
      pressure regulation that are significant in multiple resources. Three novel
      kidney-specific signals were also detected. These robustly implicated genes may
      provide new leads for therapeutic innovation.

PMID- 28740039
TI  - Isolation of Novel Bacteria Including Rarely Cultivated Phyla, Acidobacteria and
      Verrucomicrobia, from the Roots of Emergent Plants by Simple Culturing Method.
AB  - A number of novel bacteria including members of rarely cultivated phyla,
      Acidobacteria and Verrucomicrobia, were successfully isolated from the roots of
      two emergent plants, Iris pseudacorus and Scirpus juncoides, by a simple
      culturing method. A total of 47.1% (66 strains) for I. pseudacorus and 42.1% (59
      strains) for S. juncoides of all isolates (140 strains from each sample) were
      phylogenetically novel. Furthermore, Acidobacteria and Verrucomicrobia occupied
      10.7% (15 strains) and 2.9% (4 strains) of I. pseudacorus isolates, and 2.1% (3
      strains) and 3.6% (5 strains) of S. juncoides isolates, respectively, indicating
      that plant roots are attractive sources for isolating rarely cultivated microbes.

PMID- 28740045
TI  - CLINICAL FEATURES OF 15 PATIENTS UNDER SURVEILLANCE FOR RENAL MASSES.
AB  - (Objective) We investigated the clinical features of patients under surveillance
      for localized renal masses. (Methods) This study was a retrospective analysis of
      15 patients who were diagnosed as having clinically localized renal cell
      carcinoma and were placed under surveillance and 68 patients who underwent
      immediate radical operation for renal masses. (Results) The age at diagnosis in
      the surveillance group was significantly higher than in the immediate operation
      group (median, 81 vs. 65 years, respectively, P<0.01). The Charlson Comorbidity
      Index in the surveillance group was significantly higher than in the immediate
      operation group (median, 5 vs. 2, respectively, P<0.01) and 10 patients (67%) had
      complications, which was one of the reasons for surveillance. The median initial
      tumor size in the surveillance group was 2.5 cm (1.5-10.1). There was no
      significant difference in the tumor size between the two groups. During a median
      follow-up of 19 months (6-55) the median tumor growth rate was 0.29 cm per year (
      0.19-0.65) in the surveillance group. Of the 15 patients with computed tomography
      follow-up, four underwent surgical resection of the renal masses after
      surveillance. The histological diagnosis was clear cell renal cell carcinoma in
      all four. During follow-up, two patients died of other causes and one patient had
      bone metastasis but there was no death related to the renal masses in the
      surveillance group. (Conclusions) The appropriateness of the surveillance should
      be considered when we initiate surveillance for patients with renal masses
      because metastasis was detected in one patient in this study. On the other hand,
      surveillance may be an acceptable management method for elderly or severely
      comorbid patients because there were two deaths from other causes in the
      surveillance group.

PMID- 28740043
TI  - Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the
      Cell Cycle and Inducing Apoptosis.
AB  - Morphine is widely used for relieving cancer pain in patients with advanced
      cancer. However, whether morphine can suppress or promote the progression of
      cancer in breast cancer patients receiving morphine analgesia remains unclear.
      Therefore, we used an in vitro model treated with morphine and naloxone to
      investigate the effects of morphine on breast cancer cell line MCF-7. MCF-7 cells
      were cultured with different concentrations (0.01 to 10 uM) of morphine at 12th,
      24th, 36th, 48th, 60th and 72nd hours. Then, cell viability was measured through
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and
      cell cycle and apoptosis assays were detected by flow cytometry (FCM). In
      addition, cell proliferation was conducted by colony formation assay. In this
      study, we have found that morphine (0.01 to 10 uM) could significantly reduce the
      cell vitality, growth and colony formation rate of MCF-7 cells, which has a
      certain relationship with cell cycle progression arrested at the G0/G1 and G2/M
      phase and MCF-7 cells apoptosis. Moreover, naloxone along with morphine could not
      reverse these effects, which indicates that the inhibition of MCF-7 breast cancer
      cell growth and proliferation by morphine could be its independent effect, not
      associated with opioid receptors. Morphine can inhibit cell growth by blocking
      the cell cycle and promote apoptosis in MCF-7 cells. Hence, morphine may be
      unable to promote the progression of cancer in breast cancer patients receiving
      morphine analgesia.

PMID- 28740040
TI  - [Study of Interaction between Fluorinated Coating Glass and the Medicines].
AB  - The adsorption of active pharmaceutical ingredients on the surface of medical
      devices such as polyvinl chloride, ethylene-vinyl acetate copolymer and glass
      often prevent the acuurate dose of drug. At dispensing of pharmaceuticals, metre
      glass (MG) has been widely used for dispensing syrup. When measuring the viscous
      syrup, it often takes long time to dispense the accurate volume due to their
      adhesiveness on the glass surface. In this study, we investigate the adhesion of
      various syrups to MG made with uncoated glass or glass with a strongly
      hydrophobic silicone or fluorinated coating in terms of the following formulation
      parameters: viscosity, surface tension, contact angle, and surface free energy.
      The contact angles for syrups on the coated glass surfaces were significantly
      higher than those on the uncoated glass surface. In addition, the relationship
      between surface tension and contact angle was examined. We found that the contact
      angle was independent of surface tension for the uncoated glass, while it
      increased with increasing surface tension for the coated glasses. These results
      can be explained as follows: the silicone or fluorinated coatings inhibit the
      hydrogen bonding that usually takes place between water and silanol and siloxane
      groups at glass surfaces. The coatings reduced the surface free energy and
      increased the hydrophobicity of the glass, reduced its wettability by the syrups,
      and thus reduced the adhesion loss for the syrups. It was considered that as for
      the hydrophobic action, properties of matter of sample influence the coated
      device by coating in order that it is reinforced.

PMID- 28740044
TI  - Careful readings for a flash glucose monitoring system in nondiabetic Japanese
      subjects: individual differences and discrepancy in glucose concentrarion after
      glucose loading [Rapid Communication].
AB  - The FreeStyle Libre Flash Glucose Monitoring System (FGM), which can continuously
      measure glucose concentration in the interstitial fluid glucose (FGM-ISFG), has
      been in clinical use worldwide. However, it is not clear how accurately FGM-ISFG
      reflects plasma glucose concentration (PG). In the present study, we examined the
      clinical utility of FGM by oral glucose tolerance test (OGTT). In eight healthy
      volunteers (3 males; mean age, 41.8 y) wearing FGM sensors for 14 days, OGTT was
      performed during days 1-7 and days 8-14, and then both FGM-ISFG and PG were
      compared. Parkes error grid analysis indicated that all of 65 FGM-ISFG values
      were within Zone A (no effect on clinical action) and Zone B (little or no effect
      on clinical outcome). However, in OGTT, the mean FGM-ISFG was higher than the
      mean actual PG at 30, 60, and 90 minutes after loading (155.5 vs. 139.2 mg/dL,
      166.2 vs. 139.2 mg/dL, 149.5 vs. 138.2 mg/dL, respectively; p<0.05). Moreover,
      the area under the curve of FGM-ISFG was also significantly larger than that of
      PG (17,626.2 vs. 15,195.0 min.mg/dL; p<0.05). In four of eight subjects, FGM-ISFG
      tended to be higher than PG in both OGTTs, and the greatest difference between
      the two values was 58 mg/dL. FGM is useful for glycemic control, whereas it is
      not appropriate to change therapeutic regimens based on the judgment of nocturnal
      hypoglycemia and postprandial hyperglycemia by FGM-ISFG. Careful attention is
      required for proper application of FGM.

PMID- 28740046
TI  - INITIAL EXPERIENCE OF THE ENZALUTAMIDE TREATMENT FOR CASTRATION-RESISTANT
      PROSTATE CANCER.
AB  - (Objective) Enzalutamide is an oral androgen-receptor inhibitor that prolongs
      survival in men with castration-resistant prostate cancer (CRPC). We
      retrospectively evaluated clinical efficacy and safety of enzalutamide in CRPC.
      (Patients and methods) We reviewed clinical records of 73 patients who had
      received enzalutamide for the CRPC at Showa University and affiliated 7
      hospitals. Enzalutamide was given at a dose of 160 mg/day, but some patients were
      treated at lower dose because of there age or poor performance status. Prostrate
      specific antigen (PSA) response, prior docetaxel use and the previously
      administered agents were evaluated retrospectively. (Results) The median patients
      age was 77 years, the median Gleason score was 9 and the median PSA level at
      baseline was 26.9 ng/ml. The patients who had prior docetaxel use were 29 (39.7%)
      and the median of total docetaxel dose was 460 mg/body. The median number of
      total prior treatments (anti-androgens, Estramustine and steroid) was 3. Twenty
      seven (61.4%) patients with docetaxel-naive achieved over 50% reduction of PSA
      level from baseline, but only 7 (24.1%) in patients previously treated with
      docetaxel. The most common adverse events included fatigue (24.7%), anorexia
      (24.7%) and the nausea (16.4%). We found a small proportion of responders to
      enzalutamide experienced a PSA flare. (Conclusion) Our results of the use of
      Enzaltamide for CRPC were similar with previous reports. PSA flare was found in
      some patients with CRPC who responded to enzaltamide. It should be noted that
      this possible PSA flare phenomenon.

PMID- 28740047
TI  - CLINICAL OUTCOMES OF EXTERNAL-BEAM RADIOTHERAPY COMBINED WITH NEOADJUVANT
      ANDROGEN DEPRIVATION THERAPY FOR HIGH-RISK PROSTATE CANCER.
AB  - (Purpose) We investigated the outcome of external-beam radiotherapy (EBRT) with
      neoadjuvant androgen deprivation therapy (NeoADT) for high-risk prostate cancer
      defined by National Comprehensive Cancer Network (NCCN) guideline. (Patients and
      method) From 2002 to 2013, 70 patients with high-risk prostate cancer (PSA >=20
      ng/ml or clinical T stage >=T3a, Gleason score >=8) were treated with NeoADT and
      EBRT. EBRT consisted of three-dimensional conformal or intensity modulated
      radiotherapy with or without whole-pelvic radiation. Biochemical failure was
      defined according to the Phoenix definition. Biochemical progression-free
      survival (bPFS) and overall survival (OS) were calculated by Kaplan-Meier method,
      and prognostic factors for bPFS were analyzed by using the Cox proportional
      hazard model. (Result) The median age and initial prostate-specific antigen (PSA)
      level were 72 years old and 25.2 ng/ml, respectively. 43 patients had PSA level
      >=20 ng/ml, 51 patients had clinical stage >=T3a, 27 patients had Gleason score
      >=8. The number of risk factors patients possessed was 1 (RiskN-1) in 31
      patients, 2 (RiskN-2) in 27 patients and 3 (RiskN-3) in 12 patients. Median EBRT
      dose and duration of Neo ADT were 74 Gy and13.0 months, respectively. Whole
      pelvic radiation was administered in 7 patients. After median follow-up of 4.8
      years, biochemical and clinical failure occurred in 23 and 2 patients,
      respectively. No patients died of cancer. Five-year/8-year bPFS and OS were
      63%/54% and 100%/91%, respectively. In multivariate analysis, three high-risk
      factor of NCCN guideline (PSA, clinical stage, Gleason score) did not predict
      outcome after EBRT independently, but RiskN (-1 vs -2, 3, HR 35.35, 95%CI 2.51
      498.05, p<0.01) and pre-EBRT PSA (continuous, hazard ratio 1.31, 95%CI 1.01-1.71,
      p<0.05) were the significant predictors of bPFS. Five-year/8-year bPFS in RiskN-1
      group and RiskN-2 or -3 group were 89%/79% and 47%/39%, respectively. Grade 3/4
      adverse events (CTCAE ver4.0-JCOG) occurred in 2 patients. (Conclusion) Median
      dose of 74 Gy EBRT with intermediate-term NeoADT was safe and beneficial for high
      risk prostate cancer. The number of risk factors and pre-EBRT PSA level were the
      independent prognostic factors for biochemical progression-free survival.

PMID- 28740048
TI  - CLINICAL FACTORS ASSOCIATED WITH SPONTANEOUS PASSAGE OF URETER STONES IN
      CONSERVATIVE MANAGEMENT: 6 mm IN MAXIMAL STONE SIZE MEASURED BY ULTRASONOGRAPHY
      CAN BE A PREDICTIVE BORDER.
AB  - (Purpose) To date there was no consensus regarding expectant size of stone and
      time to expulsion in the conservative treatment of ureter stones. The aim of this
      study was to find the clinical factors associated with stone passage by
      evaluating the outcome of ureter stones with expectant management in Japanese.
      (Materials and methods) A total of 679 ureter stone cases who visited our
      hospital with acute real colic and/or hematuria between 2009 and 2013, and who
      had decided to be treated by expectant management with or without medical
      expulsive therapy were enrolled in this study. All cases were examined size,
      location and presence of stone, and degree of hydronephrosis with
      ultrasonography. The examined data plus clinical data such as gender, age, side
      and body mass index were analyzed to find the factors related to spontaneous
      passage of ureter stones. Statistical analysis was performed to predict whether
      the factors were associated with the ureteral stone expulsion or not. (Results)
      Accumulated residual stone curve using Kaplan-Meier method showed time to 50%
      expulsion as 15.7 days in cases with stone size no more than 6.0 mm and that as
      21.8 days in those with greater than 6.0 mm, and time to 50%-expulsion as 28.8
      days in cases with upper ureter stone whereas 15.6 days in those with middle or
      distal ureter stone. Analysis in groups with 1 mm-interval in stone size showed
      statistical significance only when compared 5-6 mm group with 6-7 mm group in
      size. Multivariate analysis showed stone size and location as statistically
      significant and independent factors to predict time to expulsion within 30 days.
      (Conclusion) Stone size and location was statistically reconfirmed to be
      associated with spontaneous passage in expectant management of ureter stones.
      This study statistically demonstrated the possibility that 6 mm in maximal stone
      size measured by ultrasonography can be a predictive border. 75% of ureter stones
      within 6 mm in maximal size measured by ultrasonography may expect to be expelled
      within 30 days.

PMID- 28740049
TI  - CLINICAL EFFICACY OF DIETARY MANIPULATION AS COMPLEMENTARY AND ALTERNATIVE
      MEDICINE THERAPIES ON FEMALE INTERSTITIAL CYSTITIS PATIENTS.
AB  - (Objectives) We examined the clinical efficacy of dietary manipulation (DM) for
      female patients with interstitial cystitis (IC) in stable condition who were
      followed in our hospital. (Patients and methods) This study included 20 female
      patients with IC in rather stable condition who were followed at our hospital. In
      cooperation with the nutrition control team, we created a basic IC diet menu for
      1 month (total daily calories, 1,500 kcal; protein, 65 g; fat, 40 g;
      carbohydrate, 220 g; water, 1,000 ml; salt, 7 g). Data regarding daily food
      intake and food-related symptoms were collected by detailed interview of each
      patient conducted by the doctors, nurses, and nutritionists at our hospital. In
      accordance with the abovementioned nutrition control, we set meal menu to control
      IC symptoms and advised the patients to reduce the intake of specific food items
      to the maximum possible extent.The following food items were removed from or
      restricted in the diet of patients: tomatoes, tomato products, soy, tofu product
      (seasoning was acceptable), spices (pepper, curry powder, mustard, horseradish,
      etc.), excessive potassium, citrus, high-acidity-inducing substances (caffeine,
      carbonate, and citric acid), etc. We evaluated the following factors to determine
      the efficacy of this diet menu 3 months after the start of the intervention:
      O'Leary-Sant symptom index (OSSI), O'Leary-Sant problem index (OSPI), urgency
      visual analogue scale (UVAS) score, (0, no urgency; 10, severe urgency), bladder
      or pelvic pain VAS (PVAS) score, (0, no pain; 10, worst possible pain), and
      numerical patient-reported quality of life (QOL) index (0, highly satisfied; 6,
      highly dissatisfied). (Results) OSSI and OSPI improved from 11.7 to 10.1
      (p<0.0001), and from 10.7 to 8.8 (p=0.01), respectively. The UVAS score
      significantly reduced from 6.4 to 4.8, and the PVAS score significantly improved
      from 6.5 to 4.8 (p<0.0001). The patient-reported QOL index significantly improved
      from 5.1 to 3.9 (p<0.0001). (Conclusion) Although repeated notes were taken and
      patients who were followed up for a long term were consulted on the meal, as
      appropriate, at the time of visit, DM was found to alleviate the symptoms of IC.
      DM as a systematic treatment modality for IC should be attempted more
      aggressively because of its non-invasiveness, without alterations to the other IC
      treatments.

PMID- 28740050
TI  - A CASE OF ADRENAL ADENOMATOID TUMOR DIAGNOSED BY IMMUNOHISTOCHEMICAL EVALUATION.
AB  - An adenomatoid tumor is a benign tumor of mesothelial derivation, typically found
      in the genital track. However, though extremely rare, an adenomatoid tumor can be
      found in the adrenal gland, making it difficult to clinically and radiologically
      differentiate it from an adrenocortical tumor or a pheochromocytoma prior to
      surgery. We encountered a-52-year old man with an adenomatoid tumor in the
      adrenal gland, who presented with an incidentally discovered left adrenal mass
      revealed by PET-CT from his regular health examinations. He had been diagnosed
      with paroxysmal hypertension two years before and was being treated with a
      hypolipidemic agent. Abdominal computed tomography revealed a left adrenal mass
      measuring 25 * 15 mm, and the findings were different from the typical
      adrenocortical adenoma or pheochromocytoma. Although laboratory examinations of
      his blood samples indicated normal adrenal function, 24-hour urine specimens
      revealed high levels of 17-OHCS, 17-KS, and catecholamine. Both 131I-MIBG
      scintigraphy and phentolamine tests showed negative findings. The patient
      underwent a laparoscopic left adrenalectomy. The cut surface of the left adrenal
      gland weighing 21 g contained a white, solid mass measuring 25 * 15 * 20 mm
      within the adrenocortical tissue. Histologically, the tumor was composed of small
      tubules lined by eosinophilic tumor cells. The tumor cells were
      immunohistochemically positive for cytokeratins and calretinin, but negative for
      steroidogenic factor-1. Therefore, based on these findings, we diagnosed this
      tumor as an adrenal adenomatoid tumor. Histopathologically, the adrenal
      adenomatoid tumor may be difficult to distinguish from an adrenocortical adenoma,
      carcinoma, lymphangioma, hemangioma, angiosarcoma, or metastatic adenocarcinoma.
      Under these conditions, immunohistochemical examination is useful for definite
      diagnosis.

PMID- 28740051
TI  - LARGE CELL CALCIFYING SERTOLI CELL TUMOR OF THE TESTIS: A CASE REPORT.
AB  - A 25 year-old man was admitted to our hospital with a left swelling testis. We
      diagnosed as left testicular tumor by ultrasound sonography and magnetic
      resonance imaging (MRI). Computed tomography (CT) showed no metastasis and tumor
      makers, betaHCG, AFP, LDH, were normal. A tumor was removed by left radical high
      orchiectomy and histological examination revealed large cell calcifying Sertoli
      cell tumor. He was given no adjuvant therapy. Neither recurrence nor metastasis
      has been found for 4 months after the operation.

PMID- 28740052
TI  - A CASE OF ADENOCARCINOMA OF THE EPIDIDYMIS WITH HYDROCELE.
AB  - A 72-year-old man presented with left scrotal swelling. The patient was diagnosed
      with left testicular hydrocele and underwent the hydrocele aspiration. However,
      it recurred within a short period. Magnetic resonance imaging (MRI) revealed a
      tumor in the epididymis and the patient then underwent left high orchiectomy. The
      histopathological examination revealed an adenocarcinoma of the epididymis. Ten
      months after the surgery, the patient has been free of disease.

PMID- 28740053
TI  - A CASE OF MULTIPLE VISCERAL INJURIES ACCOMPANIED BY RIGHT RENAL PEDICLE INJURY
      AND LEFT URETERAL DISRUPTION TREATED SUCCESSFULLY BY LEFT URETEROCALICOSTOMY.
AB  - We report a 25-year-old male with multiple visceral injuries accompanied by right
      renal pedicle injury and left ureteral disruption treated successfully by left
      ureterocalicostomy. He was accidentally crushed by a roller for fishing net
      hoists while working as a fisherman in May 2011. He was emergently transported to
      Kurobe City Hospital. He was in shock, but recovered with fluid therapy. CT
      revealed bilateral hemothorax, liver injury, bowel injury, right renal pedicle
      injury, left renal injury, and inferior vena cava damage. After bilateral chest
      drainage, emergent surgery was performed. Laparotomy revealed pancreatic injury,
      liver injury, disruption of the stomach and jejunum, colonic injury, and
      retroperitoneal hematoma on the right side. Distal pancreatectomy, hepatorrhaphy,
      left half resection of the colon, subtotal gastrectomy, and colostomy were
      performed. However, the bleeding of the right lobe of the liver could not be
      stopped, and gauze packing on the liver surface was performed for damage control.
      During the operation, right renal pedicle injury was not treated because the
      pulsation of the retroperitoneal hematoma was not palpable and the hematoma did
      not enlarge to the left side across the center; furthermore, his general
      condition was very poor. After the operation, the patient showed anuria, and
      hemodialysis was performed twice a week. One week after the operation, removal of
      the gauze was performed under general anesthesia. The gauze was removed from the
      liver while sprinkling physiological saline, and there was little bleeding.
      Tachocomb(r) (CSL Behring, Tokyo, Japan) was placed on the surface of the liver
      and a drainage tube was indwelled. Twenty-four days postoperatively, CT revealed
      left hydronephrosis with right nonfunctioning kidney, and percutaneus left
      nephrostomy was performed. Antegrade and retrograde pyelograms revealed a left
      ureteral defect of 8 cm in the upper ureter.The patient was introduced to the
      Department of Urology of Shinshu University Hospital. Left ureterocalicostomy was
      performed in January 2012, and the nephrostomy catheter was removed. The temporal
      colostomy was closed in the Department of Surgery of Kurobe City Hospital in May
      2014. He subsequently resumed his normal life.

PMID- 28740054
TI  - The Walking Recovery One Year after Surgical Management of Thoracolumbar Burst
      Fracture in Paraplegic Patients.
AB  - The aim of this study was to highlight the walking recovery after surgical
      management of traumatic burst fractures at the thoracolumbar junction (T10 or T11
      or T12 or L1) in paraplegic patients to decide what surgeons should tell their
      patients to help them develop realistic expectations and potentially improve
      their outcome. This is a series of adult patients presented with paraplegia from
      isolated thoracolumbar fracture and underwent surgical intervention from August
      2009 to August 2015. Patients with preexisting disability from previous
      neurologic condition, patients with associated severe head injury or major
      medical comorbidities or life-threatening injuries were excluded. Neurological
      status was assessed on admission using the American Spinal Injury Association
      (ASIA) impairment scale (AIS). The walking ability was assessed 12 months after
      surgery using the modified Benzel scale. This study included 53 patients with a
      mean age of 39.4 years (ranging from 18 years to 58 years). Patients presented
      with AIS grade A are 6, 18 patients with AIS grade B, and 29 patients with AIS
      grade C. All the patients with L1 fracture and 70.96% of the patients with T12
      fracture regained the ability to walk, but unfortunately all the patients with
      T10 and T11 fractures didn't regain the walking ability 12 months after surgery.
      The severity of spinal cord injury and hence the walking recovery were related to
      the spinal level of fracture. A prospectively controlled study with more patients
      is needed to reevaluate the walking recovery in paraplegic patients with T10 and
      T11 fractures.

PMID- 28740055
TI  - Prevalence of metabolically obese but normal weight (MONW) and metabolically
      healthy but obese (MHO) in Chinese Beijing urban subjects.
AB  - The aim of this study was to assess the prevalence of metabolic syndrome (MetS)
      in non-obese adults (body mass index (BMI) < 25 kg/m2) and the prevalence of
      obese adults (body mass index (BMI) >= 25 kg/m2) without MetS in Chinese Beijing
      urban subjects. A cross-sectional study was conducted and the subjects who came
      to the hospital to receive a health examination were enrolled randomly.
      Regardless of age stratification, men have a higher prevalence of MetS than
      women. Among the urban Beijing population, prevalence of metabolically obese but
      normal weight (MONW) is lower than metabolically healthy but obese (MHO)
      regardless of gender. Except for the underweight group, participants exhibit
      significant differences between MetS and non-MetS subgroups in all tested
      variables in normal weight and overweight groups, whereas MONW and MHO
      participants exhibit significant differences in all variables except for
      creatinine (CR), aspartate aminotransferase (AST), uric acid (UAC) and high
      density lipoprotein cholesterol (HDL-C). Women tend to have a higher MONW
      prevalence but lower MHO prevalence than men. Accordingly, MetS happens more
      frequently among those 40-59 yr. Besides, sex, age, WC, SBP, DBP, ALT, FG, UAC,
      TG, HDL-C and LDL-C are risk factors for MetS after multivariate adjustment. In
      conclusion, the prevalence of MONW is lower than MHO regardless of gender. Women
      tend to have a higher MONW prevalence but lower MHO prevalence than men.

PMID- 28740056
TI  - Effect of Mitral Valve Surgery in Patients With Dilated Cardiomyopathy and Severe
      Functional Mitral Regurgitation.
AB  - BACKGROUND: Surgical treatment of functional mitral regurgitation (FMR) improves
      ventricular remodeling in patients with dilated cardiomyopathy (DCM). However, it
      is unclear whether surgical treatment improves long-term outcomes. We
      investigated the effects of mitral valve (MV) surgery in patients with DCM and
      FMR.Methods and Results:Of 525 patients with DCM hospitalized due to heart
      failure between January 1996 and September 2014, 70 who had severe FMR despite
      receiving optimal medical therapy were enrolled in the study. Of these patients,
      16 underwent surgery for FMR (surgery group; repair=14, replacement=2); the
      remaining 54 who refused or decided not to undergo surgery were classified as the
      medication group. There were no differences in age, sex, medication, or
      echocardiographic parameters between the 2 groups (P>0.05). During the mean
      follow-up period of 53.6+/-43.6 months, the occurrence of clinical outcomes
      (i.e., all-cause death or left ventricular assist device implantation) was 54.3%;
      the occurrence of clinical outcomes was lower in the surgery group (P=0.008, log
      rank test). Multivariate Cox regression analysis using clinical data revealed
      that MV surgery (hazard ratio [HR] 0.257, 95% confidence interval [CI] 0.103
      0.640; P=0.004) and diabetes mellitus (HR 2.924, 95% CI 1.243-6.876; P=0.014)
      were independent predictors of clinical outcomes after adjusting for age and sex.
      CONCLUSIONS: Surgery for severe FMR provides better long-term outcomes in
      patients with DCM.

PMID- 28740057
TI  - Statin Responses in Chinese Patients.

PMID- 28740058
TI  - The Association between Social Network Betweenness and Coronary Calcium: A
      Baseline Study of Patients with a High Risk of Cardiovascular Disease.
AB  - AIM: The association of social networks with cardiovascular disease (CVD) has
      been demonstrated through various studies. This study aimed to examine the
      association between social network betweenness -a network position of mediating
      between diverse social groups-and coronary artery calcium. METHODS: The data of
      1,384 participants from the Cardiovascular and Metabolic Disease Etiology
      Research Center-High Risk Cohort, a prospective cohort study enrolling patients
      with a high risk of developing CVD (clinicaltrials.gov: NCT02003781), were
      analyzed. The deficiency in social network betweenness was measured in two ways:
      only-family networks, in which a respondent had networks with only family
      members, and no-cutpoint networks, in which the respondent does not function as a
      point of bridging between two or more social groups that are not directly
      connected. RESULTS: Participants who had higher coronary artery calcium scores
      (CACSs) were likely to have a smaller network size (p<0.001), only-family
      networks (p<0.001), and no-cutpoint networks (p<0.001). Multiple logistic
      regression analyses revealed no significant association between network size and
      CACS. Only no-cutpoint networks had a significant relationship with CACS >400
      (odds ratio, 1.72; 95% confidence interval, 1.07-2.77; p=0.026). The association
      was stronger among older (age >60 years) and female respondents. CONCLUSION:
      Deficiency in social network betweenness is closely related to coronary calcium
      in participants with a high risk of CVD. To generalize these results to a general
      population, further study should be performed.

PMID- 28740059
TI  - A case of cerebral reversible vasoconstriction syndrome triggered by repetition
      transcranial magnetic stimulation.
AB  - A 75-year-old man was admitted for combined low-frequency repetitive transcranial
      magnetic stimulation (rTMS) and intensive occupational therapy. Five days after
      the initiation of rTMS, he developed hypotension and temporary exacerbation of
      the right hemiplegia with thunderclap headache. MRA showed segmental stenosis of
      the left middle cerebral artery, which findings were improved at 9 days after the
      onset of the headache. He was diagnosed as having the reversible cerebral
      vasoconstriction syndrome (RCVS). The rTMS was recognized as safe rehabilitation
      treatment. However, it is necessary to recognize that RCVS can become one of the
      precipitants. This is the first report of RCVS triggered by rTMS.

PMID- 28740060
TI  - The effects of the Kumamoto earthquake on the clinical symptoms of patients with
      Parkinson's disease.
AB  - Our hospital is the designated treatment base for intractable neurological
      diseases in the Kumamoto Prefecture. It is located in the center of the
      prefecture where the major 7.3-magnitude Kumamoto earthquake was recorded in
      2016. In order to examine whether this earthquake affected the clinical symptoms
      of patients with Parkinson's disease in this hospital, we investigated
      outpatients examined up to 4 weeks after the earthquake. The subjects were 26
      consecutive patients without any changes in anti-Parkinson's disease treatment or
      their attending physician during the examination period. All of the items in Part
      III of the Unified Parkinson's Disease Rating Scale (UPDRS), which is a clinician
      scored scale for monitoring and evaluating motor function, were confirmed with
      the subjects before and after the earthquakes. After the earthquakes, worsened
      symptoms were found in 7 patients and 7 patients felt better. On the UPDRS,
      worsened symptoms were most commonly found among the items examining "muscle
      rigidity" and "slowness of movement and decreased movement" among the 7 patients
      with exacerbated symptoms. After the earthquake, clinical symptoms worsened
      significantly in women (P = 0.0188), patients with mild symptoms (P = 0.0111),
      and those who suffered a high degree of personal loss, such as those whose homes
      were damaged, who were forced to take refuge, or who had to sleep in their car (P
      = 0.0184). The mental and emotional burden due to the earthquake might be
      particularly high in the group of patients with worsened symptoms, suggestive of
      a relationship between stress and the exacerbation of parkinsonian symptoms.

PMID- 28740061
TI  - A case of epilepsy induced by eating or by visual stimuli of food made of minced
      meat.
AB  - We report a 34-year-old woman with eating epilepsy induced not only by eating but
      also seeing foods made of minced meat. In her early 20s of age, she started
      having simple partial seizures (SPS) as flashback and epigastric discomfort
      induced by particular foods. When she was 33 years old, she developed SPS,
      followed by secondarily generalized tonic-clonic seizure (sGTCS) provoked by
      eating a hot dog, and 6 months later, only seeing the video of dumpling. We
      performed video electroencephalogram (EEG) monitoring while she was seeing the
      video of soup dumpling, which most likely caused sGTCS. Ictal EEG showed rhythmic
      theta activity in the left frontal to mid-temporal area, followed by generalized
      seizure pattern. In this patient, seizures were provoked not only by eating
      particular foods but also by seeing these. This suggests a form of epilepsy
      involving visual stimuli.

PMID- 28740062
TI  - Intracerebral hemorrhage after intravenous recombinant tissue plasminogen
      activator (rt-PA) therapy for acute cerebral infarction in a patient with ANCA
      associated vasculitis.
AB  - We report the case of a 68-year-old man who suddenly developed right hemiparesis.
      MRI of the brain revealed a new infarction in the left corona radiata, and
      intravenous rt-PA was administered 100 minutes after the onset of symptoms. After
      the rt-PA infusion was started, his consciousness declined and the CT revealed
      bilateral intracerebral hemorrhage. His consciousness did not improve thereafter.
      He was diagnosed with ANCA-associated vasculitis owing to the high levels of MPO
      ANCA and urinary protein and the presence of erythrocytes without any other cause
      of renal damage. Although ANCA-associated vasculitis rarely involves the central
      nervous system, intracerebral hemorrhage as well as cerebral infarction may
      occur. This case provides an important opportunity to explore the implications of
      intravenous rt-PA therapy for acute cerebral infarction in patients with ANCA
      associated vasculitis.

PMID- 28740063
TI  - Difficulty in determining the association of a single nucleotide polymorphism in
      the ZNF512B gene with the risk and prognosis of amyotrophic lateral sclerosis.
AB  - The advent of next-generation sequencing technology is expected to accelerate the
      identification of novel genes, and this technology will likely supersede Sanger
      sequencing. Thus, genome-wide association studies (GWASs) are performed more
      routinely in an effort to identify disease-susceptibility genes for sporadic
      amyotrophic lateral sclerosis (ALS). Previously, a Japanese team conducted a
      large-scale GWAS with 1,305 Japanese ALS patients and discovered a new single
      nucleotide polymorphism (SNP) rs2275294 associated with susceptibility to
      sporadic ALS (sALS) in the ZNF512B gene on chromosome 20q13.33. Ju et al.
      recently performed a case-control study to examine the possible association of
      rs2275294 with the risk of sALS. Their results, however, indicated that the SNP
      in ZNF512B is not associated with sALS susceptibility in the Chinese population.
      A precise diagnosis of neurodegenerative diseases, especially ALS, is highly
      challenging. For GWASs and other clinical research studies that require a large
      sample size, if true ALS patients are not selected initially, then all subsequent
      research is futile. Here, I evaluate the factors that are likely responsible for
      the inconsistent results obtained by GWASs and propose the development of a new
      classification system and diagnostic criteria for ALS as the first step towards
      conducting better clinical studies on ALS. I have attempted to explain the
      reasons for the inconsistent association between rs2275294 and ALS progression by
      listing the gene-gene/gene-environment interactions, age of onset, sample size,
      odds ratio, and inappropriate ALS diagnosis criteria for stratifying this
      heterogeneous disease in this review.

PMID- 28740064
TI  - Successful combination immunotherapy of anti-gamma aminobutyric acid (GABA)A
      receptor antibody-positive encephalitis with extensive multifocal brain lesions.
AB  - A 78-year old woman who presented with akinetic mutism was admitted to our
      hospital. Brain MRI showed multifocal increased T2/FLAIR signal with extensive
      cortical-subcortical involvement. We suspected autoimmune encephalitis and the
      patient received methylprednisolone pulse. Her conscious level gradually
      recovered, but later relapsed again and presented with refractory status
      epilepticus. We treated her with intravenous immunoglobulin, plasma exchange and
      pulsed cyclophosphamide, with satisfactory response. A brain biopsy showed
      perivascular lymphocytic infiltrates and reactive gliosis. Anti-gamma
      aminobutyric acid (GABA)A receptor antibodies test came back to be positive after
      her recovery, and the diagnosis of anti-GABAA receptor antibody-positive
      encephalitis was made. This is a very rare case where brain biopsies were
      performed in a patient with anti-GABAA receptor antibody-positive encephalitis.

PMID- 28740065
TI  - Auditory agnosia associated with bilateral putaminal hemorrhage: A case report of
      clinical course of recovery.
AB  - A 45-year-old right-handed man with a past history (10 years) of putaminal
      hemorrage presented with auditory agnosia associated with left putaminal
      hemorrhage. It was suspected that the auditory agnosia was due to bilateral
      damage in the acoustic radiations. Generalized auditory agnosia, verbal and non
      verbal (music and environmental), was diagnosed by neuropsychological
      examinations. It improved 4 months after the onset. However, the clinical
      assessment of attention remained poor. The cognition for speech sounds improved
      slowly, but once it started to improve, the progress of improvement was rapid.
      Subsequently, the cognition for music sounds also improved, while the recovery of
      the cognition for environmental sounds remained delayed. There was a dissociation
      in recovery between these cognitions. He was able to return to work a year after
      the onset. We also reviewed the literature for cases with auditory agnosia and
      discuss their course of recovery in this report.

PMID- 28740066
TI  - Ischemic stroke with vertebrobasilar artery dissection extended to posterior
      cerebral artery.
AB  - A 45-year-old woman was admitted with headache following sudden disturbance of
      consciousness that occurred two hours beforehand. A neurological examination
      identified disorientation, left homonymous hemianopia, left hemiplegia, and
      sensory disturbance in the left limbs. Brain MRI DWI showed acute infarcts in the
      right occipital lobe and bilateral thalami, and MRA poorly depicted right
      vertebral artery and right posterior cerebral artery. Anticoagulation was started
      to treat acute ischemic stroke, but her consciousness level deteriorated at 12
      hours after onset. MRI revealed a double lumen in the basilar artery, indicating
      a diagnosis of vertebrobasilar artery dissection. Serial MRA findings showed that
      images of the basilar artery and posterior cerebral artery changed over time,
      suggesting vertebral artery dissection extension to the posterior cerebral
      artery.

PMID- 28740067
TI  - Electroretinogram (ERG) to photic stimuli should be carefully distinct from
      photic brainstem reflex in patients with deep coma.
AB  - Patient 1: A 35-year-old woman became deep coma because of intracranial
      hemorrhage after pulmonary surgery. Patient 2: A 39-year-old woman became deep
      coma because of cerebellar hemorrhage after hepatic surgery. Scalp-recorded
      digital electroencephalography (EEG) showed electrocerebral inactivity in both
      cases. In addition, both EEG showed repetitive discharges at bilateral
      frontopolar electrodes in response to photic stimuli. The amplitude and latency
      of the discharges was 17 MUV and 24 msec in case 1, and 9 MUV and 27 msec in case
      2 respectively. The activity at left frontopolar electrode disappeared after
      coverage of the ipsilateral eye. Based on these findings, we could exclude the
      possibility of brainstem response and judged it as electroretinogram (ERG).
      Photic stimulation is a useful activation method in EEG recording, and we can
      also evaluate brainstem function by checking photic blink reflex if it is evoked.
      However, we should be cautious about the distinction of ERG from photic blink
      reflex when brain death is clinically suspected.

PMID- 28740068
TI  - A Case Report of Cystic Pheochromocytoma.
AB  - BACKGROUND Pheochromocytoma is a rare catecholamine-producing tumor with an
      estimated incidence of less than 0.1% in the global population. We present a case
      of cystic pheochromocytoma that was diagnosed as an incidental finding. The
      patient presented with abdominal pain and had a history of hypertension. CASE
      REPORT A 64-year-old man with hypertension presented with a clinical history of
      intermittent abdominal pain for one year. He denied sweating, palpitations,
      headache or back pain. He was found to have an elevated blood pressure of 170/90
      and no palpable abdominal mass. Contrast-enhanced computed tomography (CT)
      imaging of the abdomen and pelvis were performed that showed cystic mass
      measuring 9 cm in diameter arising from the left adrenal gland with contrast
      enhancing mural nodules. Magnetic resonance imaging (MRI) confirmed the cystic
      nature of the mass. Laboratory analysis showed an elevated plasma normetanephrine
      (NMN) of 1,087 pg/ml and metanephrine (MN) of 372 pg/ml; 24-hour urine showed
      elevated levels of NMN and MN, 3,002 mg/24 h and 1,596 mg/24 h, respectively.
      Given the laboratory and radiologic findings, a diagnosis of cystic
      pheochromocytoma was made. After controlling blood pressure with the alpha
      blocker, doxazosin, the patient was hydrated and scheduled for an elective
      adrenalectomy. The histopathology of the excised adrenal gland was consistent
      with a cystic pheochromocytoma. CONCLUSIONS Cystic pheochromocytoma is a very
      rare tumor that may present without symptoms. The clinical course of cystic
      pheochromocytoma is similar to that of solid pheochromocytoma. Early surgical
      intervention is recommended, following blood pressure control with an alpha
      blocker, and adequate hydration.

PMID- 28740069
TI  - Acute Cellular Rejection in ABO-Incompatible Renal Transplant Recipients
      Receiving Rituximab Is Associated with Delayed-Onset Neutropenia.
AB  - BACKGROUND Rituximab induces long-lasting B cell depletion in the peripheral
      blood and increases the levels of proinflammatory cytokines associated with
      regulatory B cell depletion. Previous reports showed that B cell-related cytokine
      release after administration of rituximab may induce acute cellular rejection
      (ACR) and delayed-onset neutropenia. The present study was conducted to
      investigate the correlation between acute rejection and delayed-onset neutropenia
      in ABO-incompatible renal transplant recipients who underwent administration of
      rituximab for 1 year after transplantation. MATERIAL AND METHODS From June 2006
      to July 2015, 47 patients with chronic renal failure received ABO-incompatible
      renal transplant with rituximab induction at Osaka City University Hospital. All
      47 patients underwent plasmapheresis due to removal of anti-A/B antibodies and
      administration of rituximab, and their transplants were carried out successfully.
      We investigated the correlation between ACR and delayed-onset neutropenia in ABO
      incompatible renal transplant recipients who underwent administration of
      rituximab for 1 year after transplantation. RESULTS Fourteen patients (29.8%)
      experienced ACR (group A), and 33 recipients did not develop ACR (group B). The
      frequency of delayed-onset neutropenia was higher in group A than in group B
      (p=0.0503). Multivariate logistic regression analysis revealed that the frequency
      of ACR correlated significantly with the prevalence of delayed-onset neutropenia.
      CONCLUSIONS Our results indicated that ACR in ABO-incompatible renal transplant
      recipients receiving rituximab was associated with delayed-onset neutropenia.

PMID- 28740070
TI  - Surgery for Infective Endocarditis: Outcomes and Predictors of Mortality in 360
      Consecutive Patients.
AB  - BACKGROUND A retrospective analysis was conducted of the early and long-term
      outcomes after surgery for infective endocarditis (IE). MATERIAL AND METHODS We
      included 360 patients with IE operated upon between 1993 and 2012. The primary
      endpoint was overall cumulative postoperative survival at 30 days. Secondary
      endpoints were early postoperative outcomes and complication rates. Factors
      associated with 30-day mortality were analyzed. RESULTS Mean age was 58.7+/-14.7
      years and 26.9% (n=97) were female. The mean follow-up was 4.41+/-4.53 years.
      Postoperative survival was 81.7% at 30 days, 69.4% at 1 year, 63.3% at 5 years,
      and 63.3% at 10 years. Non-survivors were significantly older (p=0.014), with
      higher NYHA Class (p=0.002), had higher rates of preoperative diabetes mellitus
      (p=0.005), renal failure (p=0.001), and hepatic disease (p=0.002). Furthermore,
      non-survivors had higher baseline alanine aminotransferase (ALT, p=0.048),
      aspartate transaminase (AST, p=0.027), bilirubin (p=0.013), white cell count
      (WCC, p=0.034), and CRP (p=0.049). Factors associated with 30-day mortality were
      longer duration of surgery, CPB, and aortic cross-clamping times (p<0.001,
      p<0.001, and p=0.003, respectively), as well as higher RBC, FFP, and platelet
      transfusion requirements (p<0.001, p=0.005, and p<0.001, respectively).
      Multivariate logistic regression analysis revealed liver cirrhosis (OR 4.583, 95
      CI: 1.096-19.170, p=0.037) and longer CPB time (OR 1.025, 95-CI 1.008-1.042,
      p=0.004) as independent predictors of 30-day mortality. CONCLUSIONS Surgical
      treatment of IE shows satisfactory early, midterm, and long-term results.
      Multivariate logistic regression analysis revealed cirrhosis and longer CPB time
      as independent predictors of 30-day mortality.

PMID- 28740071
TI  - Prism adaptation improves egocentric but not allocentric unilateral neglect: a
      case study.
AB  - BACKGROUND: Rehabilitation of unilateral neglect has focused on the ego-centric
      form of the disturbance. However, allocentric neglect is known to predict failure
      in the activities of daily life even more than egocentric neglect. CASE REPORT:
      We submitted a patient with severe egocentric and allocentric left-sided neglect
      to an extensive prism adaptation training. After treatment, the patient persisted
      in errors on the left side of targets (allocentric neglect) and actually it
      increased in parallel with her increased exploration of left space (egocentric
      neglect). Despite the improvement in a number of cognitive and motor areas, the
      patient showed limited improvement in activities of daily living (ADL). CLINICAL
      REHABILITATION IMPACT: These observations confirm the dissociation between
      egocentric and allocentric neglect and the selective efficacy of the prism
      adaptation method on the former form. There is a need to develop new
      rehabilitation methods for allocentric neglect as this limits the complete
      recovery of patients particularly in terms of ADL.

PMID- 28740072
TI  - Long-term genomic coevolution of host-parasite interaction in the natural
      environment.
AB  - Antagonistic coevolution of parasite infectivity and host resistance may alter
      the biological functionality of species, yet these dynamics in nature are still
      poorly understood. Here we show the molecular details of a long-term phage
      bacterium arms race in the environment. Bacteria (Flavobacterium columnare) are
      generally resistant to phages from the past and susceptible to phages isolated in
      years after bacterial isolation. Bacterial resistance selects for increased phage
      infectivity and host range, which is also associated with expansion of phage
      genome size. We identified two CRISPR loci in the bacterial host: a type II-C
      locus and a type VI-B locus. While maintaining a core set of conserved spacers,
      phage-matching spacers appear in the variable ends of both loci over time. The
      spacers mostly target the terminal end of the phage genomes, which also exhibit
      the most variation across time, resulting in arms-race-like changes in the
      protospacers of the coevolving phage population.Arms races between phage and
      bacteria are well known from lab experiments, but insight from field systems is
      limited. Here, the authors show changes in the resistance and CRISPR loci of
      bacteria and the infectivity, host range and genome size of phage over multiple
      years in an aquaculture environment.

PMID- 28740073
TI  - Genome editing abrogates angiogenesis in vivo.
AB  - Angiogenesis, in which vascular endothelial growth factor receptor (VEGFR) 2
      plays an essential role, is associated with a variety of human diseases including
      proliferative diabetic retinopathy and wet age-related macular degeneration. Here
      we report that a system of adeno-associated virus (AAV)-mediated clustered
      regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease
      (Cas)9 from Streptococcus pyogenes (SpCas9) is used to deplete VEGFR2 in vascular
      endothelial cells (ECs), whereby the expression of SpCas9 is driven by an
      endothelial-specific promoter of intercellular adhesion molecule 2. We further
      show that recombinant AAV serotype 1 (rAAV1) transduces ECs of pathologic
      vessels, and that editing of genomic VEGFR2 locus using rAAV1-mediated
      CRISPR/Cas9 abrogates angiogenesis in the mouse models of oxygen-induced
      retinopathy and laser-induced choroid neovascularization. This work establishes a
      strong foundation for genome editing as a strategy to treat angiogenesis
      associated diseases.Abnormal angiogenesis causes many ocular diseases. Here the
      authors employ CRISPR/Cas9 gene editing technology to silence VEGFR2, a major
      regulator of angiogenesis, in retinal endothelium and abrogate angiogenesis in
      the mouse models of oxygen-induced retinopathy and laser-induced choroid
      neovascularization.

PMID- 28740074
TI  - CDKL5 localizes at the centrosome and midbody and is required for faithful cell
      division.
AB  - The cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with rare
      neurodevelopmental disorders characterized by the early onset of seizures and
      intellectual disability. The CDKL5 protein is widely expressed in most tissues
      and cells with both nuclear and cytoplasmic localization. In post-mitotic neurons
      CDKL5 is mainly involved in dendritic arborization, axon outgrowth, and spine
      formation while in proliferating cells its function is still largely unknown.
      Here, we report that CDKL5 localizes at the centrosome and at the midbody in
      proliferating cells. Acute inactivation of CDKL5 by RNA interference (RNAi) leads
      to multipolar spindle formation, cytokinesis failure and centrosome accumulation.
      At the molecular level, we observed that, among the several midbody components we
      analyzed, midbodies of CDKL5-depleted cells were devoid of HIPK2 and its
      cytokinesis target, the extrachromosomal histone H2B phosphorylated at S14. Of
      relevance, expression of the phosphomimetic mutant H2B-S14D, which is capable of
      overcoming cytokinesis failure in HIPK2-defective cells, was sufficient to rescue
      spindle multipolarity in CDKL5-depleted cells. Taken together, these results
      highlight a hitherto unknown role of CDKL5 in regulating faithful cell division
      by guaranteeing proper HIPK2/H2B functions at the midbody.

PMID- 28740075
TI  - The lipid peroxidation product 4-hydroxynonenal contributes to oxidative stress
      mediated deterioration of the ageing oocyte.
AB  - An increase in intraovarian reactive oxygen species (ROS) has long been
      implicated in the decline in oocyte quality associated with maternal ageing.
      Oxidative stress (OS)-induced lipid peroxidation and the consequent generation of
      highly electrophilic aldehydes, such as 4-hydroxynonenal (4-HNE), represents a
      potential mechanism by which ROS can inflict damage in the ageing oocyte. In this
      study, we have established that aged oocytes are vulnerable to damage by 4-HNE
      resulting from increased cytosolic ROS production within the oocyte itself.
      Further, we demonstrated that the age-related induction of OS can be
      recapitulated by exposure of germinal vesicle (GV) oocytes to exogenous H2O2.
      Such treatments stimulated an increase in 4-HNE generation, which remained
      elevated during in vitro oocyte maturation to metaphase II. Additionally,
      exposure of GV oocytes to either H2O2 or 4-HNE resulted in decreased meiotic
      completion, increased spindle abnormalities, chromosome misalignments and
      aneuploidy. In seeking to account for these data, we revealed that proteins
      essential for oocyte health and meiotic development, namely alpha-, beta-, and
      gamma-tubulin are vulnerable to adduction via 4-HNE. Importantly, 4-HNE-tubulin
      adduction, as well as increased aneuploidy rates, were resolved by co-treatment
      with the antioxidant penicillamine, demonstrating a possible therapeutic
      mechanism to improve oocyte quality in older females.

PMID- 28740076
TI  - Atomic-resolution imaging of electrically induced oxygen vacancy migration and
      phase transformation in SrCoO2.5-sigma.
AB  - Oxygen ion transport is the key issue in redox processes. Visualizing the process
      of oxygen ion migration with atomic resolution is highly desirable for designing
      novel devices such as oxidation catalysts, oxygen permeation membranes, and solid
      oxide fuel cells. Here we show the process of electrically induced oxygen
      migration and subsequent reconstructive structural transformation in a SrCoO2.5
      sigma film by scanning transmission electron microscopy. We find that the
      extraction of oxygen from every second SrO layer occurs gradually under an
      electrical bias; beyond a critical voltage, the brownmillerite units collapse
      abruptly and evolve into a periodic nano-twined phase with a high c/a ratio and
      distorted tetrahedra. Our results show that oxygen vacancy rows are not only
      natural oxygen diffusion channels, but also preferred sites for the induced
      oxygen vacancies. These direct experimental results of oxygen migration may
      provide a common mechanism for the electrically induced structural evolution of
      oxides.Information on how oxygen ions transport is crucial to understanding field
      induced phase transformations in materials. Here, Zhang et al. directly image
      atomic-scale oxygen migration and the subsequent structural reconstruction in a
      SrCoO2.5-sigma film in the presence of an electric field.

PMID- 28740077
TI  - Footprint-free human fetal foreskin derived iPSCs: A tool for modeling
      hepatogenesis associated gene regulatory networks.
AB  - Induced pluripotent stem cells (iPSCs) are similar to embryonic stem cells and
      can be generated from somatic cells. We have generated episomal plasmid-based and
      integration-free iPSCs (E-iPSCs) from human fetal foreskin fibroblast cells
      (HFF1). We used an E-iPSC-line to model hepatogenesis in vitro. The HLCs were
      characterized biochemically, i.e. glycogen storage, ICG uptake and release, UREA
      and bile acid production, as well as CYP3A4 activity. Ultra-structure analysis by
      electron microscopy revealed the presence of lipid and glycogen storage, tight
      junctions and bile canaliculi- all typical features of hepatocytes. Furthermore,
      the transcriptome of undifferentiated E-iPSC, DE, HE and HLCs were compared to
      that of fetal liver and primary human hepatocytes (PHH). K-means clustering
      identified 100 clusters which include developmental stage-specific groups of
      genes, e.g. OCT4 expression at the undifferentiated stage, SOX17 marking the DE
      stage, DLK and HNF6 the HE stage, HNF4alpha and Albumin is specific to HLCs,
      fetal liver and adult liver (PHH) stage. We use E-iPSCs for modeling gene
      regulatory networks associated with human hepatogenesis and gastrulation in
      general.

PMID- 28740078
TI  - Synthesis of ordered carbonaceous frameworks from organic crystals.
AB  - Despite recent advances in the carbonization of organic crystalline solids like
      metal-organic frameworks or supramolecular frameworks, it has been challenging to
      convert crystalline organic solids into ordered carbonaceous frameworks. Herein,
      we report a route to attaining such ordered frameworks via the carbonization of
      an organic crystal of a Ni-containing cyclic porphyrin dimer (Ni2-CPDPy). This
      dimer comprises two Ni-porphyrins linked by two butadiyne (diacetylene) moieties
      through phenyl groups. The Ni2-CPDPy crystal is thermally converted into a
      crystalline covalent-organic framework at 581 K and is further converted into
      ordered carbonaceous frameworks equipped with electrical conductivity by
      subsequent carbonization at 873-1073 K. In addition, the porphyrin's Ni-N4 unit
      is also well retained and embedded in the final framework. The resulting ordered
      carbonaceous frameworks exhibit an intermediate structure, between organic-based
      frameworks and carbon materials, with advantageous electrocatalysis. This
      principle enables the chemical molecular-level structural design of three
      dimensional carbonaceous frameworks.Carbon-based materials are promising
      alternatives to noble metal catalysts, but their structures are typically
      disordered and difficult to control. Here, the authors obtain ordered
      carbonaceous frameworks with advantageous electrocatalytic properties via the
      carbonization of nickel-containing porphyrin dimer networks.

PMID- 28740079
TI  - An integrated strategy by using target tissue metabolomics biomarkers as
      pharmacodynamic surrogate indices to screen antipyretic components of
      Qingkaikling injection.
AB  - Traditional Chinese medicine (TCM) treatment can be valuable therapeutic
      strategies. However, the active components and action mechanisms that account for
      its therapeutic effects remain elusive. Based on the hypothesis that the
      components of a formula which exert effect would be measurable in target tissue,
      a target tissue metabolomics-based strategy was proposed for screening of
      antipyretic components in Qingkaikling injection (QKLI). First, we detected the
      components of QKLI which could reach its target tissue (hypothalamus) by
      determining the hypothalamus microdialysate and discovered that only baicalin and
      geniposide could be detected. Then, by conducting hypothalamus metabolomics
      studies, 14 metabolites were screened as the potential biomarkers that related to
      the antipyretic mechanisms of QKLI and were used as its pharmacodynamic surrogate
      indices. Subsequently, the dynamic concentration of baicalin and geniposide in
      hypothalamus microdialysates and biomarkers in hypothalamus were measured and
      correlated with each other. The results indicated that only baicalin shown a good
      correlation with these biomarkers. Finally, a network pharmacology approach was
      established to validate the antipyretic activity of baicalin and the results
      elucidated its antipyretic mechanisms as well. The integrated strategy proposed
      here provided a powerful means for identifying active components and mechanisms
      contributing to pharmacological effects of TCM.

PMID- 28740081
TI  - Photosynthetic capacity of senescent leaves for a subtropical broadleaf deciduous
      tree species Liquidambar formosana Hance.
AB  - Photosynthetic capacity and leaf life span generally determine how much carbon a
      plant assimilates during the growing season. Leaves of deciduous tree species
      start senescence in late season, but whether the senescent leaves still retain
      capacity of carbon assimilation remains a question. In this study, we
      investigated leaf phenology and photosynthesis of a subtropical broadleaf
      deciduous tree species Liquidambar formosana Hance in the central southern
      continental China. The results show that L. formosana has extended leaf
      senescence (more than 2 months) with a substantial number of red leaves
      persisting on the tree. Leaf photosynthetic capacity decreases over season, but
      the senescent red leaves still maintain relatively high photosynthetic capacity
      at 42%, 66% and 66% of the mature leaves for net photosynthesis rate, apparent
      quantum yield, and quantum yield at the light compensation point, respectively.
      These results indicate that L. formosana may still contribute to carbon sink
      during leaf senescence.

PMID- 28740080
TI  - A new marine-derived sulfoglycolipid triggers dendritic cell activation and
      immune adjuvant response.
AB  - Dendritic Cells (DCs) recognize infectious non-self molecules and engage the
      adaptive immune system thereby initiating long lasting, antigen-specific
      responses. As such, the ability to activate DCs is considered a key tool to
      enhance the efficacy and quality of vaccination. Here we report a novel
      immunomodulatory sulfolipid named beta-SQDG18 that prototypes a class of natural
      derived glycolipids able to prime human DCs by a TLR2/TLR4-independent mechanism
      and trigger an efficient immune response in vivo. beta-SQDG18 induces maturation
      of DC with the upregulation of MHC II molecules and co-stimulatory proteins
      (CD83, CD86), as well as pro-inflammatory cytokines (IL-12 and INF-gamma). Mice
      immunized with OVA associated to beta-SQDG18 (1:500) produced a titer of anti-OVA
      Ig comparable to traditional adjuvants. In an experimental model of melanoma,
      vaccination of C57BL/6 mice with beta-SQDG18-adjuvanted hgp10 peptide elicited a
      protective response with a reduction in tumour growth and increase in survival.

PMID- 28740082
TI  - High risk of unprecedented UK rainfall in the current climate.
AB  - In winter 2013/14 a succession of storms hit the UK leading to record rainfall
      and flooding in many regions including south east England. In the Thames river
      valley there was widespread flooding, with clean-up costs of over L1 billion.
      There was no observational precedent for this level of rainfall. Here we present
      analysis of a large ensemble of high-resolution initialised climate simulations
      to show that this event could have been anticipated, and that in the current
      climate there remains a high chance of exceeding the observed record monthly
      rainfall totals in many regions of the UK. In south east England there is a 7%
      chance of exceeding the current rainfall record in at least one month in any
      given winter. Expanding our analysis to some other regions of England and Wales
      the risk increases to a 34% chance of breaking a regional record somewhere each
      winter.A succession of storms during the 2013-2014 winter led to record flooding
      in the UK. Here, the authors use high-resolution climate simulations to show that
      this event could have been anticipated and that there remains a high chance of
      exceeding observed record monthly rainfall totals in many parts of the UK.

PMID- 28740083
TI  - PLATE-Seq for genome-wide regulatory network analysis of high-throughput screens.
AB  - Pharmacological and functional genomic screens play an essential role in the
      discovery and characterization of therapeutic targets and associated
      pharmacological inhibitors. Although these screens affect thousands of gene
      products, the typical readout is based on low complexity rather than genome-wide
      assays. To address this limitation, we introduce pooled library amplification for
      transcriptome expression (PLATE-Seq), a low-cost, genome-wide mRNA profiling
      methodology specifically designed to complement high-throughput screening assays.
      Introduction of sample-specific barcodes during reverse transcription supports
      pooled library construction and low-depth sequencing that is 10- to 20-fold less
      expensive than conventional RNA-Seq. The use of network-based algorithms to infer
      protein activity from PLATE-Seq data results in comparable reproducibility to 30
      M read sequencing. Indeed, PLATE-Seq reproducibility compares favorably to other
      large-scale perturbational profiling studies such as the connectivity map and
      library of integrated network-based cellular signatures.Despite the importance of
      pharmacological and functional genomic screens the readouts are of low
      complexity. Here the authors introduce PLATE-Seq, a low-cost genome-wide mRNA
      profiling method to complement high-throughput screening.

PMID- 28740084
TI  - Ryanodine receptors are part of the myospryn complex in cardiac muscle.
AB  - The Cardiomyopathy-associated gene 5 (Cmya5) encodes myospryn, a large tripartite
      motif (TRIM)-related protein found predominantly in cardiac and skeletal muscle.
      Cmya5 is an expression biomarker for a number of diseases affecting striated
      muscle and may also be a schizophrenia risk gene. To further understand the
      function of myospryn in striated muscle, we searched for additional myospryn
      paralogs. Here we identify a novel muscle-expressed TRIM-related protein
      minispryn, encoded by Fsd2, that has extensive sequence similarity with the C
      terminus of myospryn. Cmya5 and Fsd2 appear to have originated by a chromosomal
      duplication and are found within evolutionarily-conserved gene clusters on
      different chromosomes. Using immunoaffinity purification and mass spectrometry we
      show that minispryn co-purifies with myospryn and the major cardiac ryanodine
      receptor (RyR2) from heart. Accordingly, myospryn, minispryn and RyR2 co-localise
      at the junctional sarcoplasmic reticulum of isolated cardiomyocytes. Myospryn
      redistributes RyR2 into clusters when co-expressed in heterologous cells whereas
      minispryn lacks this activity. Together these data suggest a novel role for the
      myospryn complex in the assembly of ryanodine receptor clusters in striated
      muscle.

PMID- 28740085
TI  - Improved memory for information learnt before alcohol use in social drinkers
      tested in a naturalistic setting.
AB  - Alcohol is known to facilitate memory if given after learning information in the
      laboratory; we aimed to investigate whether this effect can be found when alcohol
      is consumed in a naturalistic setting. Eighty-eight social drinkers were randomly
      allocated to either an alcohol self-dosing or a sober condition. The study
      assessed both retrograde facilitation and alcohol induced memory impairment using
      two independent tasks. In the retrograde task, participants learnt information in
      their own homes, and then consumed alcohol ad libitum. Participants then
      undertook an anterograde memory task of alcohol impairment when intoxicated. Both
      memory tasks were completed again the following day. Mean amount of alcohol
      consumed was 82.59 grams over the evening. For the retrograde task, as predicted,
      both conditions exhibited similar performance on the memory task immediately
      following learning (before intoxication) yet performance was better when tested
      the morning after encoding in the alcohol condition only. The anterograde task
      did not reveal significant differences in memory performance post-drinking. Units
      of alcohol drunk were positively correlated with the amount of retrograde
      facilitation the following morning. These findings demonstrate the retrograde
      facilitation effect in a naturalistic setting, and found it to be related to the
      self-administered grams of alcohol.

PMID- 28740087
TI  - High Contrast Far-Field Radiative Thermal Diode.
AB  - We propose a theoretical concept of a far-field radiative thermal rectification
      device that uses a phase change material to achieve a high degree of asymmetry in
      radiative heat transfer. The proposed device has a multilayer structure on one
      side and a blackbody on other side. The multilayer structure consists of
      transparent thin film of KBr sandwiched between a thin film of VO2 and a
      reflecting layer of gold. When VO2 is in its insulating phase, the structure is
      highly reflective due to the two transparent layers on highly reflective gold.
      When VO2 is in the metallic phase, Fabry-Perot type of resonance occurs and the
      tri-layer structure acts like a wide-angle antireflection coating achieved by
      destructive interference of partially reflected waves making it highly absorptive
      for majority of spectral range of thermal radiation. The proposed structure forms
      the active part of configuration that acts like a far-field radiative thermal
      diode. Thermal rectification greater than 11 is obtained for a temperature bias
      of 20 K, which is the highest rectification ever predicted for far-field
      radiative diode configurations.

PMID- 28740086
TI  - Novel Molecule Exhibiting Selective Affinity for GABAA Receptor Subtypes.
AB  - Aminoquinoline derivatives were evaluated against a panel of
      receptors/channels/transporters in radioligand binding experiments. One of these
      derivatives (DCUK-OEt) displayed micromolar affinity for brain gamma-aminobutyric
      acid type A (GABAA) receptors. DCUK-OEt was shown to be a positive allosteric
      modulator (PAM) of GABA currents with alpha1beta2gamma2, alpha1beta3gamma2,
      alpha5beta3gamma2 and alpha1beta3delta GABAA receptors, while having no
      significant PAM effect on alphabeta receptors or alpha1beta1gamma2,
      alpha1beta2gamma1, alpha4beta3gamma2 or alpha4beta3delta receptors. DCUK-OEt
      modulation of alpha1beta2gamma2 GABAA receptors was not blocked by flumazenil.
      The subunit requirements for DCUK-OEt actions distinguished DCUK-OEt from other
      currently known modulators of GABA function (e.g., anesthetics, neurosteroids or
      ethanol). Simulated docking of DCUK-OEt at the GABAA receptor suggested that its
      binding site may be at the alpha + beta- subunit interface. In slices of the
      central amygdala, DCUK-OEt acted primarily on extrasynaptic GABAA receptors
      containing the alpha1 subunit and generated increases in extrasynaptic "tonic"
      current with no significant effect on phasic responses to GABA. DCUK-OEt is a
      novel chemical structure acting as a PAM at particular GABAA receptors. Given
      that neurons in the central amygdala responding to DCUK-OEt were recently
      identified as relevant for alcohol dependence, DCUK-OEt should be further
      evaluated for the treatment of alcoholism.

PMID- 28740088
TI  - Functional correlates of TSH, fT3 and fT4 in Alzheimer disease: a F-18 FDG PET/CT
      study.
AB  - The present study was aimed to investigate the relationships between thyroid
      stimulating hormone (TSH), freeT3 (fT3) and freeT4 (fT4) and brain glucose
      consumption as detectable by means of 2-deoxy-2-(F-18) fluoro-D-glucose (F-18
      FDG) Positron Emission Tomography/Computed Tomography (PET/CT) in a selected
      population with Alzheimer disease (AD). We evaluated 87 subjects (37 males and 50
      females, mean age 70 (+/-6) years old) with AD. All of them were subjected to
      TSH, fT3 and fT4 assay and to cerebrospinal fluid amyloid (Abeta1-42) and tau
      [phosphorylated-tau (p-tau) and total-tau (t-tau)] assay prior PET/CT
      examination. Values for TSH, fT3 and fT4 were in the normal range. The
      relationships were evaluated by means of statistical parametric mapping (SPM8)
      using age, sex, MMSE, scholarship and CSF values of amyloid and tau as
      covariates. We found a significant positive correlation between TSH values and
      cortical glucose consumption in a wide portion of the anterior cingulate cortex
      bilaterally (BA32) and left frontal lobe (BA25) (p FWE-corr <0.001; p FDRcorr
      <0.000; cluster extent 66950). No significant relationships were found between
      cortical F-18 FDG uptake and T3 and T4 serum levels. The results of our study
      suggest that a cortical dysfunction in anterior cingulate and frontal lobes may
      affect serum values of TSH in AD patients.

PMID- 28740089
TI  - Effects of growth rate and promoter activity on single-cell protein expression.
AB  - Protein expression in a single cell depends on its global physiological state.
      Moreover, genetically-identical cells exhibit variability (noise) in protein
      expression, arising from the stochastic nature of biochemical processes, cell
      growth and division. While it is well understood how cellular growth rate
      influences mean protein expression, little is known about the relationship
      between growth rate and noise in protein expression. Here we quantify this
      relationship in Bacillus subtilis by a novel combination of experiments and
      theory. We measure the effects of promoter activity and growth rate on the
      expression of a fluorescent protein in single cells. We disentangle the observed
      protein expression noise into protein-specific and systemic contributions, using
      theory and variance decomposition. We find that noise in protein expression
      depends solely on mean expression levels, regardless of whether expression is set
      by promoter activity or growth rate, and that noise increases linearly with
      growth rate. Our results can aid studies of (synthetic) gene circuits of single
      cells and their condition dependence.

PMID- 28740090
TI  - Chaotic time series prediction for glucose dynamics in type 1 diabetes mellitus
      using regime-switching models.
AB  - In patients with type 1 diabetes mellitus (T1DM), glucose dynamics are influenced
      by insulin reactions, diet, lifestyle, etc., and characterized by instability and
      nonlinearity. With the objective of a dependable decision support system for T1DM
      self-management, we aim to model glucose dynamics using their nonlinear chaotic
      properties. A group of patients was monitored via continuous glucose monitoring
      (CGM) sensors for several days under free-living conditions. We assessed the
      glycemic variability (GV) and chaotic properties of each time series. Time series
      were subsequently transformed into the phase-space and individual autoregressive
      (AR) models were applied to predict glucose values over 30-minute and 60-minute
      prediction horizons (PH). The logistic smooth transition AR (LSTAR) model
      provided the best prediction accuracy for patients with high GV. For a PH of 30
      minutes, the average values of root mean squared error (RMSE) and mean absolute
      error (MAE) for the LSTAR model in the case of patients in the hypoglycemia range
      were 5.83 ( +/- 1.95) mg/dL and 5.18 ( +/- 1.64) mg/dL, respectively. For a PH of
      60 minutes, the average values of RMSE and MAE were 7.43 ( +/- 1.87) mg/dL and
      6.54 ( +/- 1.6) mg/dL, respectively. Without the burden of measuring exogenous
      information, nonlinear regime-switching AR models provided fast and accurate
      results for glucose prediction.

PMID- 28740091
TI  - microRNA-mediated differential expression of TRMU, GTPBP3 and MTO1 in cell models
      of mitochondrial-DNA diseases.
AB  - Mitochondrial diseases due to mutations in the mitochondrial (mt) DNA are
      heterogeneous in clinical manifestations but usually include OXPHOS dysfunction.
      Mechanisms by which OXPHOS dysfunction contributes to the disease phenotype
      invoke, apart from cell energy deficit, maladaptive responses to mitochondria-to
      nucleus retrograde signaling. Here we used five different cybrid models of mtDNA
      diseases to demonstrate that the expression of the nuclear-encoded mt-tRNA
      modification enzymes TRMU, GTPBP3 and MTO1 varies in response to specific
      pathological mtDNA mutations, thus altering the modification status of mt-tRNAs.
      Importantly, we demonstrated that the expression of TRMU, GTPBP3 and MTO1 is
      regulated by different miRNAs, which are induced by retrograde signals like ROS
      and Ca2+ via different pathways. Our data suggest that the up- or down-regulation
      of the mt-tRNA modification enzymes is part of a cellular response to cope with a
      stoichiometric imbalance between mtDNA- and nuclear-encoded OXPHOS subunits.
      However, this miRNA-mediated response fails to provide full protection from the
      OXPHOS dysfunction; rather, it appears to aggravate the phenotype since
      transfection of the mutant cybrids with miRNA antagonists improves the energetic
      state of the cells, which opens up options for new therapeutic approaches.

PMID- 28740092
TI  - An adaptive image enhancement method for a recirculating aquaculture system.
AB  - Due to the low and uneven illumination that is typical of a recirculating
      aquaculture system (RAS), visible and near infrared (NIR) images collected from
      RASs always have low brightness and contrast. To resolve this issue, this paper
      proposes an image enhancement method based on the Multi-Scale Retinex (MSR)
      algorithm and a greyscale nonlinear transformation. First, the images are
      processed using the MSR algorithm to eliminate the influence of low and uneven
      illumination. Then, the normalized incomplete Beta function is used to perform a
      greyscale nonlinear transformation. The function's optimal parameters (alpha and
      beta) are automatically selected by the particle swarm optimization (PSO)
      algorithm based on an image contrast measurement function. This adaptive image
      enhancement method is compared with other classic enhancement methods. The
      results show that the proposed method greatly improves the image contrast and
      highlights dark areas, which is helpful during further analysis of these images.

PMID- 28740093
TI  - Stable isotopes reveal the effect of trawl fisheries on the diet of commercially
      exploited species.
AB  - Bottom trawling can change food availability for benthivorous demersal species by
      (i) changing benthic prey composition through physical seabed impacts and (ii) by
      removing overall benthic consumer biomass increasing the net availability of
      benthic prey for remaining individuals. Thus trawling may both negatively and
      positively influence the quantity and quality of food available. Using delta 13C
      and delta 15N we investigated potential diet changes of three commercially
      exploited species across trawling gradients in the Kattegat (plaice, dab and
      Norway lobster (Nephrops)) and the Irish Sea (Nephrops). In the Kattegat,
      trawling affected primarily the biomass of benthic consumers, lowering
      competition. Nephrops showed significant positive relationships for delta 13C and
      a domed relationship for delta 15N with trawling. In the Irish Sea, intense
      trawling had a negative effect on benthic prey. delta 13C and delta 15N thus
      showed the inverse relationships to those observed in the Kattegat. Plaice from
      the Kattegat, showed a significant relationship with trawling intensity for delta
      13C, but not for delta 15N. No relationship was found for dab. Changes of delta
      13C and delta 15N correlated with changes in condition of species. The results
      show that the removal of demersal competitors and benthos by trawling can change
      the diets of commercial species, ultimately affecting their body condition.

PMID- 28740094
TI  - Fibulin-3 promotes osteosarcoma invasion and metastasis by inducing epithelial to
      mesenchymal transition and activating the Wnt/beta-catenin signaling pathway.
AB  - This study explored the role of fibulin-3 in osteosarcoma progression and the
      possible signaling pathway involved. Fibulin-3 mRNA and protein expression in
      normal tissue, benign fibrous dysplasia, osteosarcoma, osteosarcoma cell lines
      (HOS and U-2OS), the normal osteoblastic cell line hFOB, and different invasive
      subclones was evaluated by immunohistochemistry (IHC) or immunocytochemistry
      (ICC) and real time reverse transcriptase-polymerase chain reaction (real time
      qRT-PCR). To assess the role of fibulin-3 in the invasion and metastasis of
      osteosarcoma cells, lentiviral vectors with fibulin-3 small hairpin RNA (shRNA)
      and pLVX-fibulin-3 were constructed and used to infect the highly invasive and
      low invasive subclones. The effects of fibulin-3 knockdown and upregulation on
      the biological behavior of osteosarcoma cells were investigated by functional in
      vitro and in vivo assays. The results revealed that fibulin-3 expression was
      upregulated in osteosarcoma, and was positively correlated with low
      differentiation, lymph node metastasis, and poor prognosis. Fibulin-3 could
      promote osteosarcoma cell invasion and metastasis by inducing EMT and activating
      the Wnt/beta-catenin signaling pathway. Collectively, our findings demonstrate
      that fibulin-3 is a promoter of osteosarcoma development and progression, and
      suggest a novel therapeutic target for future studies.

PMID- 28740095
TI  - Phylodynamics of major CRF01_AE epidemic clusters circulating in mainland of
      China.
AB  - As the most dominant HIV-1 strain in China, CRF01_AE needs to have its
      evolutionary and demographic history documented. In this study, we provide
      phylogenetic analysis of all CRF01_AE pol sequences identified in mainland China.
      CRF01_AE sequences were collected from the Los Alamos HIV Sequence Database and
      the local Chinese provincial centers of disease control and prevention.
      Phylogenetic trees were constructed to identify major epidemic clusters. Bayesian
      coalescent-based method was used to reconstruct the time scale and demographic
      history. There were 2965 CRF01_AE sequences from 24 Chinese provinces that were
      collected, and 5 major epidemic clusters containing 85% of the total CRF01_AE
      sequences were identified. Every cluster contains sequences from more than 10
      provinces with 1 or 2 dominant transmission routes. One cluster arose in the
      1990s and 4 clusters arose in the 2000s. Cluster I is in the decline stage, while
      the other clusters are in the stable stage. Obvious lineage can be observed among
      sequences from the same transmission route but not the same area. Two large
      clusters in high-level prevalence were found in MSM (Men who have sex with men),
      which highlighted that more emphasis should be placed on MSM for HIV control in
      mainland China.

PMID- 28740096
TI  - Associations of plasma homocysteine levels with peripheral systolic blood
      pressure and noninvasive central systolic blood pressure in a community-based
      Chinese population.
AB  - Previous studies indicated that homocysteine (Hcy) is associated with higher
      peripheral systolic blood pressure (pSBP). There have been few data on the
      relationship between Hcy and central SBP (cSBP). A total of 4,364 Chinese
      subjects from the Shijingshan community in Beijing were included. cSBP and pSBP
      were measured with an Omron HEM-9000AI device. Subjects were 57.20 +/- 8.9 years
      old, 37.9% were male. The median of Hcy was 11.96 MUmol/L. The mean of cSBP and
      pSBP was 129.94 +/- 18.03 mmHg and 133.25 +/- 18.58 mmHg. lnHcy was associated
      with cSBP (adjusted beta = 2.17, SE = 0.80, P = 0.007) and pSBP (adjusted beta =
      2.42, SE = 0.75, P = 0.001). With increasing Hcy, there were enhanced
      correlations of Hcy with pSBP and cSBP (p for trend between quartiles <0.01).
      Using Q1 for reference, the Q4 was associated with cSBP (adjusted beta = 1.77, SE
      = 0.89, P = 0.047) and pSBP (adjusted beta = 2.15, SE = 0.84, P = 0.011). The
      correlations were more significant in non-obese subjects than in obese subjects
      (cSBP: beta = 4.30 vs 0.46, pSBP: beta = 5.04 vs 1.18, P for interaction <0.001).
      Our study showed that Hcy was associated with higher cSBP and pSBP, especially in
      non-obese subjects.

PMID- 28740097
TI  - The Frustration-induced Ferroelectricity of a Manganite Tricolor Superlattice
      with Artificially Broken Symmetry.
AB  - In this paper, [(La0.9Sr0.1MnO3)n/(Pa0.9Ca0.1MnO3)n/(La0.9Sb0.1MnO3)n]m
      superlattices films have been deposited on (001) Nb:SrTiO3 substrates by a laser
      molecular-beam epitaxy technology. Expected ferroelectricity arise at well
      defined tricolor superlattice at low temperature, composed of transition metal
      manganite, which is absent in the single-phase compounds. Furthermore, the
      ferroelectric properties of the superlattices are enhanced by increasing the
      periodicity m, which may be attributed to the accumulation of the polarization
      induced by the frustration. As for the magnetic hysteresis loop characteristics
      of the multilayer structures, the saturation magnetization and magnetic
      coercivity of films present definitely a strong periodic dependence. It also
      indicates that the frustration may exist in the tricolor superlattice. Our
      results further verify the previous theoretical research of generating
      multiferroics experimentally paving a way for designing or developing the novel
      magnetoelectric devices based on manganite ferromagnets.

PMID- 28740099
TI  - Freeze-drying of mammalian cells using trehalose: preservation of DNA integrity.
AB  - The aim of this study was to investigate preservation of biomolecular structures,
      particularly DNA, in freeze-dried fibroblasts, after loading with trehalose via
      freezing-induced uptake. Cells were freeze-dried with trehalose alone or in a
      mixture of albumin and trehalose. Albumin was added to increase the glass
      transition temperature and storage stability. No viable cells were recovered
      after freeze-drying and rehydration. FTIR studies showed that membrane phase
      behavior of freeze-dried cells resembles that of fresh cells. However, one day
      after rehydration membrane phase separation was observed, irrespective of the
      presence or absence of trehalose during freeze-drying. Freeze-drying did not
      affect the overall protein secondary structure. Analysis of DNA damage via single
      cell gel electrophoresis ('comet assay') showed that DNA damage progressively
      increased with storage duration and temperature. DNA damage was prevented during
      storage at 4  degrees C. It is shown that trehalose reduces DNA damage during
      storage, whereas addition of albumin did not seem to have an additional
      protective effect on storage stability (i.e. DNA integrity) despite the fact that
      albumin increased the glass transition temperature. Taken together, DNA in freeze
      dried somatic cells can be preserved using trehalose as protectant and storage at
      or below 4  degrees C.

PMID- 28740098
TI  - Puerarin ameliorated the behavioral deficits induced by chronic stress in rats.
AB  - The present study aimed to investigate the mechanisms underlying the
      antidepressant-like effects of puerarin via the chronic unpredictable stress
      (CUS) procedure in rats. Similar to Sertraline (Ser), Chronic treatment of
      puerarin (60 and 120 mg/kg, i.g) elicited the antidepressant-like effects by
      reversing the decreased sucrose preference in sucrose preference test (SPT), by
      blocking the increased latency to feed in novelty-suppressed feeding test (NSFT)
      and the increased immobility time in forced swimming test (FST) without affecting
      locomotor activity. However, acute puerarin treatment did not ameliorate the
      antidepressant- and anxiolytic- like effects in FST and NSFT, respectively. In
      addition, enzyme linked immunosorbent assay (ELISA) and high performance liquid
      chromatography-electrochemical detection (HPLC-ECD) showed that chronic treatment
      of puerarin (60 and 120 mg/kg, i.g) reversed the decreased levels of
      progesterone, allopregnanolone, serotonin (5-HT) and 5-Hydroxyindoleacetic acid
      (5-HIAA) in prefrontal cortex and hippocampus of post-CUS rats. Furthermore,
      puerarin (60 and 120 mg/kg, i.g) blocked the increased corticotropin releasing
      hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH).
      Collectively, repeated administration of puerarin alleviated the behavioral
      deficits induced by chronic stress which was associated with the biosynthesis of
      neurosteroids, normalization of serotonergic system and preventing HPA axis
      dysfunction.

PMID- 28740100
TI  - Quantification of cell-bubble interactions in a 3D engineered tissue phantom.
AB  - Understanding cell-bubble interactions is crucial for preventing bubble related
      pathologies and harnessing their potential therapeutic benefits. Bubbles can
      occur in the body as a result of therapeutic intravenous administration, surgery,
      infections or decompression. Subsequent interactions with living cells, may
      result in pathological responses such as decompression sickness (DCS). This work
      investigates the interactions that occur between bubbles formed during
      decompression and cells in a 3D engineered tissue phantom. Increasing the tissue
      phantoms' cellular density resulted in decreased dissolved O2 (DO) concentrations
      (p = 0.0003) measured using real-time O2 monitoring. Direct microscopic
      observation of these phantoms, revealed a significant (p = 0.0024) corresponding
      reduction in bubble nucleation. No significant difference in growth rate or
      maximum size of the bubbles was measured (p = 0.99 and 0.23). These results show
      that bubble nucleation is dominated by DO concentration (affected by cellular
      metabolism), rather than potential nucleation sites provided by cell-surfaces.
      Consequent bubble growth depends not only on DO concentration but also on
      competition for dissolved gas. Cell death was found to significantly increase (p
      = 0.0116) following a bubble-forming decompression. By comparison to 2D
      experiments; the more biomimetic 3D geometry and extracellular matrix in this
      work, provide data more applicable for understanding and developing models of in
      vivo bubble dynamics.

PMID- 28740101
TI  - p38 MAPK signaling and phosphorylations in the BRCT1 domain regulate XRCC1
      recruitment to sites of DNA damage.
AB  - XRCC1 is a scaffold protein involved in base excision repair and single strand
      break repair. It is a phosphoprotein that contains more than 45 phosphorylation
      sites, however only a few of these have been characterized and connected to
      specific kinases and functions. Mitogen activated protein kinases (MAPK) are
      mediators of cellular stress responses, and here we demonstrate that p38 MAPK
      signaling is involved in phosphorylation of XRCC1 and regulation of recruitment
      to oxidative stress. Inhibition of p38 MAPK caused a marked pI shift of XRCC1
      towards a less phosphorylated state. Inhibition of p38 also increased the
      immediate accumulation of XRCC1 at site of DNA damage in a poly(ADP)-ribose (PAR)
      dependent manner. These results suggest a link between PARylation, p38 signaling
      and XRCC1 recruitment to DNA damage. Additionally, we characterized two
      phosphorylation sites, T358 and T367, located within, or close to, the phosphate
      binding pocket of XRCC1, which is important for interaction with PAR. Mutation of
      these sites impairs recruitment of XRCC1 to DNA damage and binding to PARP1/PAR.
      Collectively, our data suggest that phosphorylation of T358 and T367 and p38
      signaling are important for proper regulation of XRCC1 recruitment to DNA damage
      and thereby avoidance of potential toxic and mutagenic BER-intermediates.

PMID- 28740102
TI  - Niosomes: A Strategy toward Prevention of Clinically Significant Drug
      Incompatibilities.
AB  - Drug incompatibilities are considered as one of the most critical problems in
      intensive care units. In the current study, the ability of nanomaterials to
      prevent drug incompatibilities in clinical settings has been investigated. As a
      proof-of-concept, the ability of niosomes to prevent physical and chemical
      incompatibilities that occur upon mixing acyclovir and vancomycin during
      management of acute meningitis has been explored. Nanosized spherical particles
      loaded separately with either vancomycin or acyclovir, with high entrapment
      efficiency (ca. 46-56%), could be prepared, and sustained release of their
      entrapped cargoes have been demonstrated over time. We have shown that
      precipitation, degradation and loss of biological activity of drugs occurred upon
      mixing solutions of the free drugs. On the contrary, drugs loaded separately
      inside niosomal structures exhibited high stability, exceptional physical and
      chemical compatibilities for up to 48 h with complete preservation of the
      antimicrobial activity of vancomycin. This study opens a venue for a new spectrum
      of applications of nanomaterials in preventing clinically significant drug
      incompatibilities, aiming at the reduction of adverse reactions, cost and
      hospitalization period, and improvement of patient compliance and therapeutic
      outcomes.

PMID- 28740103
TI  - A self-supporting bimetallic Au@Pt core-shell nanoparticle electrocatalyst for
      the synergistic enhancement of methanol oxidation.
AB  - The morphology of Pt-Au bimetal nanostructures plays an important role in
      enhancing the catalytic capability, catalytic stability and utilization
      efficiency of the platinum. We designed and successfully prepared Au@Pt
      nanoparticles (NPs) through an economical, surfactant-free and efficient method
      of seed-mediated growth. The Au@Pt NPs displayed electrochemical performances
      superior to those of commercial Pt/C catalysts because their agglomeration was
      prevented and exhibited better long-term stability with respect to methanol
      oxidation in acidic media by efficiently removing intermediates. Among the
      obtained Au@Pt NPs, Au90@Pt10 NPs exhibited the most significantly enhanced
      catalytic performance for the methanol oxidation reaction (MOR). Their mass and
      electrochemically active surface area (ECSA)-normalized current densities are
      approximately 3.9 and 4.6 times higher than those of commercial Pt/C catalysts,
      respectively. The oxidation current densities of the Au90@Pt10 NPs are
      approximately 1.8 times higher than those of commercial Pt/C catalysts after 4000
      s of continuous measurement because the small Pt NPs grown on the surface of the
      Au90@Pt10 NPs were effectively stabilized by the Au metal support. This approach
      may be a facile method for the synthesis of self-supported bimetallic
      nanostructures, which is of great significance for the development of high
      performance electrocatalysts and sensors.

PMID- 28740104
TI  - Host seeking parasitic nematodes use specific odors to assess host resources.
AB  - Entomopathogenic nematodes (EPNs) are insect parasites used as biological control
      agents. Free-living infective juveniles (IJs) of EPNs employ host-seeking
      behaviors to locate suitable hosts for infection. We found that EPNs can
      differentiate between naive and infected hosts, and that host attractiveness
      changes over time in a species-specific manner. We used solid-phase
      microextraction and gas chromatography/mass spectrometry to identify volatile
      chemical cues that may relay information about a potential host's infection
      status and resource availability. Among the chemicals identified from the
      headspace of infected hosts, 3-Methyl-2-buten-1-ol (prenol) and 3-Hydroxy-2
      butanone (AMC) were selected for further behavioral assays due to their temporal
      correlation with the behavioral changes of IJs towards the infected hosts. Both
      compounds were repulsive to IJs of Steinernema glaseri and S. riobrave in a dose
      dependent manner when applied on an agar substrate. Furthermore, the repulsive
      effects of prenol were maintained when co-presented with the uninfected host
      odors, overriding attraction to uninfected hosts. Prenol was attractive to dauers
      of some free-living nematodes and insect larvae. These data suggest that host
      associated chemical cues may have several implications in EPN biology, not only
      as signals for avoidance and dispersal of conspecifics, but also as attractants
      for new potential hosts.

PMID- 28740105
TI  - A brief exposure to cadmium impairs Leydig cell regeneration in the adult rat
      testis.
AB  - Cadmium is an endocrine disruptor, impairing male reproduction. The objective of
      this study is to investigate whether cadmium affects rat Leydig cell regeneration
      and to dissect the underlying mechanism. Adult male Sprague-Dawley rats received
      a single intraperitoneal injection (i.p.) of 0, 0.5 or 1.0 mg/kg of cadmium
      chloride, followed by ethane dimethane sulfonate (EDS) treatment to eliminate
      adult Leydig cells 20 days later. Compared to control (0 dose), cadmium treatment
      reduced serum testosterone levels by days 21, 35, and 56 after EDS treatment.
      Serum luteinizing hormone (LH) levels were also affected by day 56, the only time
      point examined. There were fewer regenerated Leydig cells in the cadmium-treated
      testis on days 35 and 56 after EDS treatment. Further studies demonstrated that
      the mRNA or protein levels of Leydig (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1,
      Cyp17a1, Hsd17b3, and Hsd11b1), non-Leydig (Fshr and Dhh), and gonadotroph (Lhb)
      cells were also significantly lower in cadmium-treated animals. Since LH and
      desert hedgehog (DHH) are critical factors for Leydig cell differentiation, our
      result demonstrated that the lower doses of cadmium exposure, even briefly, may
      permanently damage Leydig cell regeneration.

PMID- 28740106
TI  - Environment Changes Genetic Effects on Respiratory Conditions and Allergic
      Phenotypes.
AB  - The prevalence of asthma and allergic diseases is disproportionately distributed
      among different populations, with an increasing trend observed in Western
      countries. Here we investigated how the environment affected genotype-phenotype
      association in a genetically homogeneous, but geographically separated
      population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding
      to 8 genes (ADAM33, ALOX5, LT-alpha, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-alpha),
      the lung function and five respiratory/allergic conditions (ever asthma,
      bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing
      either in the westernized environment of Denmark or in the rural area of
      Greenland. Our results showed that lung function was associated with genetic
      variants in ORMDL3, with polymorphisms having a significant interaction with
      place of residence. LT-alpha SNP rs909253 and rs1041981 were significantly
      associated with bronchitis risk. LT-alpha SNP rs2844484 was related to dermatitis
      susceptibility and was significantly influenced by the place of residence. The
      observed gene-phenotype relationships were exclusively present in one population
      and absent in the other population. We conclude that the genotype-phenotype
      associations relating to bronchitis and allergy susceptibility are dependent on
      the environment and that environmental factors/lifestyles modify genetic
      predisposition and change the genetic effects on diseases.

PMID- 28740107
TI  - Flexible interlocked porous frameworks allow quantitative photoisomerization in a
      crystalline solid.
AB  - Photochromic molecules have shown much promise as molecular components of stimuli
      responsive materials, but despite recent achievements in various photoresponsive
      materials, quantitative conversion in photochemical reactions in solids is
      hampered by the lack of intrinsic structural flexibility available to release
      stress and strain upon photochemical events. This issue remains one of the
      challenges in developing solid-state photoresponsive materials. Here, we report a
      strategy to realize photoresponsive crystalline materials showing quantitative
      reversible photochemical reactions upon ultraviolet and visible light irradiation
      by introducing structural flexibility into crystalline porous frameworks with a
      twofold interpenetration composed of a diarylethene-based ligand. The structural
      flexibility of the porous framework enables highly efficient photochemical
      electrocyclization in a single-crystal-to-single-crystal manner. CO2 sorption on
      the porous crystal at 195 K is reversibly modulated by light irradiation, and
      coincident X-ray powder diffraction/sorption measurements clearly demonstrate the
      flexible nature of the twofold interpenetrated frameworks.Organizing photochromic
      molecules into 3D networks is a key strategy to access photoresponsive materials,
      but framework rigidity typically limits conversion efficiency. Here, the authors
      exploit a flexible metal-organic framework to achieve quantitative and reversible
      photoisomerization in a porous crystalline solid.

PMID- 28740108
TI  - Replication of H9 influenza viruses in the human ex vivo respiratory tract, and
      the influence of neuraminidase on virus release.
AB  - H9N2 viruses are the most widespread influenza viruses in poultry in Asia. We
      evaluated the infection and tropism of human and avian H9 influenza virus in the
      human respiratory tract using ex vivo respiratory organ culture. H9 viruses
      infected the upper and lower respiratory tract and the majority of H9 viruses had
      a decreased ability to release virus from the bronchus rather than the lung. This
      may be attributed to a weak neuraminidase (NA) cleavage of carbon-6-linked sialic
      acid (Sia) rather than carbon-3-linked Sia. The modified cleavage of N
      acetlylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) by NA in
      H9 virus replication was observed by reverse genetics, and recombinant H9N2
      viruses with amino acids (38KQ) deleted in the NA stalk, and changing the amino
      acid at position 431 from Proline-to-Lysine. Using recombinant H9 viruses
      previously evaluated in the ferret, we found that viruses which replicated well
      in the ferret did not replicate to the same extent in the human ex vivo cultures.
      The existing risk assessment models for H9N2 viruses in ferrets may not always
      have a strong correlation with the replication in the human upper respiratory
      tract. The inclusion of the human ex vivo cultures would further strengthen the
      future risk-assessment strategies.

PMID- 28740110
TI  - Neuroblastoma: Tumours get super-enhanced.

PMID- 28740109
TI  - Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and
      autophagy activation.
AB  - Hypoxia regulates autophagy and nucleotide-binding oligomerization domain
      receptor, pyrin domain containing (NLRP)3, two innate immune mechanisms linked by
      mutual regulation and associated to IBD. Here we show that hypoxia ameliorates
      inflammation during the development of colitis by modulating autophagy and
      mammalian target of rapamycin (mTOR)/NLRP3 pathway. Hypoxia significantly reduces
      tumor necrosis factor alpha, interleukin (IL)-6 and NLRP3 expression, and
      increases the turnover of the autophagy protein p62 in colon biopsies of Crohn's
      disease patients, and in samples from dextran sulfate sodium-treated mice and Il
      10 -/- mice. In vitro, NF-kappaB signaling and NLRP3 expression are reduced
      through hypoxia-induced autophagy. We also identify NLRP3 as a novel binding
      partner of mTOR. Dimethyloxalylglycine-mediated hydroxylase inhibition
      ameliorates colitis in mice, downregulates NLRP3 and promotes autophagy. We
      suggest that hypoxia counteracts inflammation through the downregulation of the
      binding of mTOR and NLRP3 and activation of autophagy.Hypoxia and HIF-1alpha
      activation are protective in mouse models of colitis, and the latter regulates
      autophagy. Here Cosin-Roger et al. show that hypoxia ameliorates intestinal
      inflammation in Crohn's patients and murine colitis models by inhibiting
      mTOR/NLRP3 pathway and promoting autophagy.

PMID- 28740112
TI  - Epigenetics: Tumour suppressive HIF2alpha.

PMID- 28740111
TI  - Therapeutic resistance: Transcribing patterns of resistance.

PMID- 28740113
TI  - Tumour immunology: Tumours copy to escape.

PMID- 28740114
TI  - Tumour vaccines: Personal training by vaccination.

PMID- 28740116
TI  - Tumour immunology: Feeding frenzy.

PMID- 28740115
TI  - Chemotherapy: Neutrophils deliver the goods.

PMID- 28740118
TI  - Leukaemia: Multiple origins of relapse.

PMID- 28740117
TI  - Fragile sites in cancer: more than meets the eye.
AB  - Ever since initial suggestions that instability at common fragile sites (CFSs)
      could be responsible for chromosome rearrangements in cancers, CFSs and
      associated genes have been the subject of numerous studies, leading to questions
      and controversies about their role and importance in cancer. It is now clear that
      CFSs are not frequently involved in translocations or other cancer-associated
      recurrent gross chromosome rearrangements. However, recent studies have provided
      new insights into the mechanisms of CFS instability, their effect on genome
      instability, and their role in generating focal copy number alterations that
      affect the genomic landscape of many cancers.

PMID- 28740120
TI  - Uncovering Offshore Financial Centers: Conduits and Sinks in the Global Corporate
      Ownership Network.
AB  - Multinational corporations use highly complex structures of parents and
      subsidiaries to organize their operations and ownership. Offshore Financial
      Centers (OFCs) facilitate these structures through low taxation and lenient
      regulation, but are increasingly under scrutiny, for instance for enabling tax
      avoidance. Therefore, the identification of OFC jurisdictions has become a
      politicized and contested issue. We introduce a novel data-driven approach for
      identifying OFCs based on the global corporate ownership network, in which over
      98 million firms (nodes) are connected through 71 million ownership relations.
      This granular firm-level network data uniquely allows identifying both sink-OFCs
      and conduit-OFCs. Sink-OFCs attract and retain foreign capital while conduit-OFCs
      are attractive intermediate destinations in the routing of international
      investments and enable the transfer of capital without taxation. We identify 24
      sink-OFCs. In addition, a small set of five countries - the Netherlands, the
      United Kingdom, Ireland, Singapore and Switzerland - canalize the majority of
      corporate offshore investment as conduit-OFCs. Each conduit jurisdiction is
      specialized in a geographical area and there is significant specialization based
      on industrial sectors. Against the idea of OFCs as exotic small islands that
      cannot be regulated, we show that many sink and conduit-OFCs are highly developed
      countries.

PMID- 28740121
TI  - Overexpression of DNMT3b target genes during Enteric Nervous System development
      contribute to the onset of Hirschsprung disease.
AB  - Hirschsprung disease (HSCR) is attributed to a failure of neural crest cells
      (NCCs) to migrate, proliferate, differentiate and/or survive in the bowel wall
      during embryonic Enteric Nervous System (ENS) development. ENS formation is the
      result from a specific gene expression pattern regulated by epigenetic events,
      such DNA methylation by the DNA methyltransferases (DNMTs), among other
      mechanisms. Specifically, DNMT3b de novo methyltransferase is associated with
      NCCs development and has been shown to be implicated in ENS formation and in
      HSCR. Aiming to elucidate the specific mechanism underlying the DNMT3b role in
      such processes, we have performed a chromatin immunoprecipitation coupled with
      massively parallel sequencing analysis to identify the DNMT3B target genes in
      enteric precursor cells (EPCs) from mice. Moreover, the expression patterns of
      those target genes have been analyzed in human EPCs from HSCR patients in
      comparison with controls. Additionally, we have carried out a search of rare
      variants in those genes in a HSCR series. Through this approach we found 9 genes
      showing a significantly different expression level in both groups. Therefore,
      those genes may have a role in the proper human ENS formation and a failure in
      their expression pattern might contribute to this pathology.

PMID- 28740119
TI  - Novel insights into mesothelioma biology and implications for therapy.
AB  - Malignant mesothelioma is a universally lethal cancer that is increasing in
      incidence worldwide. There is a dearth of effective therapies, with only one
      treatment (pemetrexed and cisplatin combination chemotherapy) approved in the
      past 13 years. However, the past 5 years have witnessed an exponential growth in
      our understanding of mesothelioma pathobiology, which is set to revolutionize
      therapeutic strategies. From a genomic standpoint, mesothelioma is characterized
      by a preponderance of tumour suppressor alterations, for which novel therapies
      are currently in development. Other promising antitumour agents include
      inhibitors against angiogenesis, mesothelin and immune checkpoints, which are at
      various phases of clinical trial testing.

PMID- 28740122
TI  - Recent increases in terrestrial carbon uptake at little cost to the water cycle.
AB  - Quantifying the responses of the coupled carbon and water cycles to current
      global warming and rising atmospheric CO2 concentration is crucial for predicting
      and adapting to climate changes. Here we show that terrestrial carbon uptake
      (i.e. gross primary production) increased significantly from 1982 to 2011 using a
      combination of ground-based and remotely sensed land and atmospheric
      observations. Importantly, we find that the terrestrial carbon uptake increase is
      not accompanied by a proportional increase in water use (i.e. evapotranspiration)
      but is largely (about 90%) driven by increased carbon uptake per unit of water
      use, i.e. water use efficiency. The increased water use efficiency is positively
      related to rising CO2 concentration and increased canopy leaf area index, and
      negatively influenced by increased vapour pressure deficits. Our findings suggest
      that rising atmospheric CO2 concentration has caused a shift in terrestrial water
      economics of carbon uptake.The response of the coupled carbon and water cycles to
      anthropogenic climate change is unclear. Here, the authors show that terrestrial
      carbon uptake increased significantly from 1982 to 2011 and that this increase is
      largely driven by increased water-use efficiency, rather than an increase in
      water use.

PMID- 28740123
TI  - Piezomagnetism and magnetoelastic memory in uranium dioxide.
AB  - The thermal and magnetic properties of uranium dioxide, a prime nuclear fuel and
      thoroughly studied actinide material, remain a long standing puzzle, a result of
      strong coupling between magnetism and lattice vibrations. The magnetic state of
      this cubic material is characterized by a 3-k non-collinear antiferromagnetic
      structure and multidomain Jahn-Teller distortions, likely related to its
      anisotropic thermal properties. Here we show that single crystals of uranium
      dioxide subjected to strong magnetic fields along threefold axes in the magnetic
      state exhibit the abrupt appearance of positive linear magnetostriction, leading
      to a trigonal distortion. Upon reversal of the field the linear term also
      reverses sign, a hallmark of piezomagnetism. A switching phenomenon occurs at +/
      18 T, which persists during subsequent field reversals, demonstrating a robust
      magneto-elastic memory that makes uranium dioxide the hardest piezomagnet known.
      A model including a strong magnetic anisotropy, elastic, Zeeman, Heisenberg
      exchange, and magnetoelastic contributions to the total energy is proposed.The
      nuclear fuel uranium dioxide is of intrinsic interest due to its industrial
      applications but it also exhibits intriguing electronic and magnetic properties.
      Here, the authors demonstrate how its complex magnetic structure and interactions
      give rise to a strong piezomagnetic effect.

PMID- 28740124
TI  - Evaluation of Sofosbuvir (beta-D-2'-deoxy-2'-alpha-fluoro-2'-beta-C
      methyluridine) as an inhibitor of Dengue virus replication.
AB  - We evaluated Sofosbuvir (SOF), the anti-hepatitis C virus prodrug of beta-d-2'
      deoxy-2'-alpha-fluoro-2'-beta-C-methyluridine-5'-monophosphate, for potential
      inhibitory activity against DENV replication. Both cell-based and biochemical
      assays, based on use of purified DENV full-length NS5 enzyme, were studied.
      Cytopathic effect protection and virus yield reduction assays confirmed that SOF
      possessed anti-DENV activity in cell culture with a 50% effective concentration
      (EC50) of 4.9 uM and 1.4 uM respectively. Real-time RT-PCR verified that SOF
      inhibits generation of viral RNA with an EC50 of 9.9 uM. Purified DENV NS5
      incorporated the active triphosphate form (SOF-TP) into nascent RNA, causing
      chain-termination. Relative to the natural UTP, the incorporation efficiency of
      SOF-TP was low (discrimination value = 327.5). In a primer extension assay, SOF
      TP was active against DENV NS5 wild-type polymerase activity with an IC50 of 14.7
      +/- 2.5 uM. The S600T substitution in the B Motif of DENV polymerase conferred
      4.3-fold resistance to SOF-TP; this was due to decreased incorporation efficiency
      rather than enhanced excision of the incorporated SOF nucleotide. SOF has
      antiviral activity against DENV replication. The high discrimination value in
      favor of UTP in enzyme assays may not necessarily preclude antiviral activity in
      cells. SOF may be worthy of evaluation against severe DENV infections in humans.

PMID- 28740125
TI  - APOE genotype influences insulin resistance, apolipoprotein CII and CIII
      according to plasma fatty acid profile in the Metabolic Syndrome.
AB  - Metabolic markers associated with the Metabolic Syndrome (MetS) may be affected
      by interactions between the APOE genotype and plasma fatty acids (FA). In this
      study, we explored FA-gene interactions between the missense APOE polymorphisms
      and FA status on metabolic markers in MetS. Plasma FA, blood pressure, insulin
      sensitivity and lipid concentrations were determined at baseline and following a
      12-week randomized, controlled, parallel, dietary FA intervention in 442 adults
      with MetS (LIPGENE study). FA-APOE gene interactions at baseline and following
      change in plasma FA were assessed using adjusted general linear models. At
      baseline E4 carriers had higher plasma concentrations of total cholesterol (TC),
      low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) compared
      with E2 carriers; and higher TC, LDL-C and apo B compared with E3/E3. Whilst
      elevated plasma n-3 polyunsaturated FA (PUFA) was associated with a beneficially
      lower concentration of apo CIII in E2 carriers, a high proportion of plasma C16:0
      was associated with insulin resistance in E4 carriers. Following FA intervention,
      a reduction in plasma long-chain n-3 PUFA was associated with a reduction in apo
      CII concentration in E2 carriers. Our novel data suggest that individuals with
      MetS may benefit from personalized dietary interventions based on APOE genotype.

PMID- 28740127
TI  - Three-Dimensional Imaging of Biological Tissue by Cryo X-Ray Ptychography.
AB  - High-throughput three-dimensional cryogenic imaging of thick biological specimens
      is valuable for identifying biologically- or pathologically-relevant features of
      interest, especially for subsequent correlative studies. Unfortunately, high
      resolution imaging techniques at cryogenic conditions often require sample
      reduction through sequential physical milling or sectioning for sufficient
      penetration to generate each image of the 3-D stack. This study represents the
      first demonstration of using ptychographic hard X-ray tomography at cryogenic
      temperatures for imaging thick biological tissue in a chemically-fixed, frozen
      hydrated state without heavy metal staining and organic solvents. Applied to
      mammalian brain, this label-free cryogenic imaging method allows visualization of
      myelinated axons and sub-cellular features such as age-related pigmented cellular
      inclusions at a spatial resolution of ~100 nanometers and thicknesses approaching
      100 microns. Because our approach does not require dehydration, staining or
      reduction of the sample, we introduce the possibility for subsequent analysis of
      the same tissue using orthogonal approaches that are expected to yield direct
      complementary insight to the biological features of interest.

PMID- 28740126
TI  - Evasion of immunosurveillance by genomic alterations of PPARgamma/RXRalpha in
      bladder cancer.
AB  - Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited
      therapeutic options. Although immunotherapies are approved for MIBC, the majority
      of patients fail to respond, suggesting existence of complementary immune evasion
      mechanisms. Here, we report that the PPARgamma/RXRalpha pathway constitutes a
      tumor-intrinsic mechanism underlying immune evasion in MIBC. Recurrent mutations
      in RXRalpha at serine 427 (S427F/Y), through conformational activation of the
      PPARgamma/RXRalpha heterodimer, and focal amplification/overexpression of
      PPARgamma converge to modulate PPARgamma/RXRalpha-dependent transcription
      programs. Immune cell-infiltration is controlled by activated PPARgamma/RXRalpha
      that inhibits expression/secretion of inflammatory cytokines. Clinical data sets
      and an in vivo tumor model indicate that PPARgammaHigh/RXRalphaS427F/Y impairs
      CD8+ T-cell infiltration and confers partial resistance to immunotherapies.
      Knockdown of PPARgamma or RXRalpha and pharmacological inhibition of PPARgamma
      significantly increase cytokine expression suggesting therapeutic approaches to
      reviving immunosurveillance and sensitivity to immunotherapies. Our study reveals
      a class of tumor cell-intrinsic "immuno-oncogenes" that modulate the immune
      microenvironment of cancer.Muscle-invasive bladder cancer (MIBC) is a potentially
      lethal disease. Here the authors characterize diverse genetic alterations in MIBC
      that convergently lead to constitutive activation of PPARgamma/RXRalpha and
      result in immunosurveillance escape by inhibiting CD8+ T-cell recruitment.

PMID- 28740128
TI  - Updating the list of known opioids through identification and characterization of
      the new opioid derivative 3,4-dichloro-N-(2-(diethylamino)cyclohexyl)-N
      methylbenzamide (U-49900).
AB  - New psychoactive substances have been rapidly growing in popularity in the drug
      market as non-illegal drugs. In the last few years, an increment has been
      reported on the use of synthetic alternatives to heroin, the synthetic opioids.
      Based on the information provided by the European Monitoring Centre for Drug and
      Drug Addiction, these synthetic opioids have been related to overdoses and deaths
      in Europe and North America. One of these opioids is the U-47700. A few months
      ago, U-47700 was scheduled in the U.S. and other countries, and other opioid
      derivatives have been appearing in order to replace it. One of these compounds is
      U-49900, an analog of U-47700. A white powder sample was obtained from an
      anonymous user in Spain. After an accurate characterization by gas chromatography
      mass spectrometry, ultra-high performance liquid chromatography-high resolution
      mass spectrometry, nuclear magnetic resonance and single-crystal X-ray
      diffraction; and complemented by Fourier-transformed infrared spectroscopy,
      ultraviolet and circular dichroism spectrophotometry, the drug sample was
      unequivocally identified as U-49900. The information provided will be useful for
      the Early Warning System and forensic laboratories for future identifications of
      the U-49900, as well as in tentative identifications of other related opioids.

PMID- 28740129
TI  - Evaluation of high resolution ultrasound as a tool for assessing the 3D volume of
      blood clots during in vitro thrombolysis.
AB  - Thrombosis is a major cause of several diseases, i.e. myocardial infarction,
      cerebral stroke and pulmonary embolism. Thrombolytic therapies are required to
      induce fast and efficient recanalization of occluded vessels. To evaluate the in
      vitro efficacy of these thrombolytic strategies, measuring clot dissolution is
      essential. This study aimed to evaluate and validate high resolution ultrasound
      as a tool to assess the exact volume of clots in 3D and in real time during in
      vitro thrombolytic drug testing. This new method was validated by measuring the
      effects of concentration range of recombinant tissue type plasminogen activator
      on a blood clot during complete occlusion or 70% stenosis of a vessel. This study
      shows that high resolution ultrasound imaging allows for a real-time assessment
      of the 3D volume of a blood clot with negligible inter- and intra-operator
      variabilities. The conclusions drawn from this study demonstrate the promising
      potential of high resolution ultrasound imaging for the in vitro assessment of
      new thrombolytic drugs.

PMID- 28740130
TI  - Obesity, adipokines, and C-peptide are associated with distinct plasma
      phospholipid profiles in adult males, an untargeted lipidomic approach.
AB  - Obesity is associated with dysregulated lipid metabolism and adipokine secretion.
      Our group has previously reported obesity and adipokines are associated with %
      total fatty acid (FA) differences in plasma phospholipids. The objective of our
      current study was to identify in which complex lipid species (i.e.,
      phosphatidylcholine, sphingolipids, etc) these FA differences occur. Plasma
      lipidomic profiling (n = 126, >95% Caucasian, 48-65 years) was performed using
      chromatographic separation and high resolution tandem mass spectrometry. The
      responses used in the statistical analyses were body mass index (BMI), waist
      circumference (WC), serum adipokines, cytokines, and a glycemic marker. High
      dimensional statistical analyses were performed, all models were adjusted for age
      and smoking, and p-values were adjusted for false discovery. In Bayesian models,
      the lipidomic profiles (over 1,700 lipids) accounted for >60% of the inter
      individual variation of BMI, WC, and leptin in our population. Across statistical
      analyses, we report 51 individual plasma lipids were significantly associated
      with obesity. Obesity was inversely associated lysophospholipids and ether linked
      phosphatidylcholines. In addition, we identify several unreported lipids
      associated with obesity that are not present in lipid databases. Taken together,
      these results provide new insights into the underlying biology associated with
      obesity and reveal new potential pathways for therapeutic targeting.

PMID- 28740131
TI  - Hybrid normal metal/ferromagnetic nanojunctions for domain wall tracking.
AB  - Hybrid normal metal/ferromagnetic, gold/permalloy (Au/Py), nanojunctions are used
      to investigate magnetoresistance effects and track magnetization spatial
      distribution in L-shaped Py nanostructures. Transversal and longitudinal
      resistances are measured and compared for both straight and 90 degrees  corner
      sections of the Py nanostructure. Our results demonstrate that the absolute
      change in resistance is larger in the case of longitudinal measurements. However,
      due to the small background resistance, the relative change in the transversal
      resistance along the straight section is several orders of magnitude larger than
      the analogous longitudinal variation. These results prove that hybrid
      nanojunctions represent a significant improvement with respect to previously
      studied all-ferromagnetic crosses, as they also reduce the pinning potential at
      the junction and allow probing the magnetization locally. In addition, unusual
      metastable states with longitudinal domain walls along Py straight sections are
      observed. Micromagnetic simulations in combination with a magnetotransport model
      allow interpretation of the results and identification of the observed
      transitions.

PMID- 28740132
TI  - Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat
      diet-induced obesity in mice due to defective lipid absorption.
AB  - Tissue inhibitor of metalloproteases (TIMPs) are inhibitors of matrix
      metalloproteinases (MMPs) that regulate tissue extracellular matrix (ECM)
      turnover. TIMP4 is highly expressed in adipose tissue, its levels are further
      elevated following high-fat diet, but its role in obesity is unknown. Eight-week
      old wild-type (WT) and Timp4-knockout (Timp4 -/-) mice received chow or high fat
      diet (HFD) for twelve weeks. Timp4 -/- mice exhibited a higher food intake but
      lower body fat gain. Adipose tissue of Timp4 -/- -HFD mice showed reduced
      hypertrophy and fibrosis compared to WT-HFD mice. Timp4 -/- -HFD mice were also
      protected from HFD-induced liver and skeletal muscle triglyceride accumulation
      and dyslipidemia. Timp4 -/--HFD mice exhibited reduced basic metabolic rate and
      energy expenditure, but increased respiratory exchange ratio. Increased free
      fatty acid excretion was detected in Timp4 -/--HFD compared to WT-HFD mice. CD36
      protein, the major fatty acid transporter in the small intestine, increased with
      HFD in WT but not in Timp4 -/- mice, despite a similar rise in Cd36 mRNA in both
      genotypes. Consistently, HFD increased enterocyte lipid content only in WT but
      not in Timp4 -/- mice. Our study reveals that absence of TIMP4 can impair lipid
      absorption and the high fat diet-induced obesity in mice possibly by regulating
      the proteolytic processing of CD36 protein in the intestinal enterocytes.

PMID- 28740133
TI  - Spatial cycles mediated by UNC119 solubilisation maintain Src family kinases
      plasma membrane localisation.
AB  - The peripheral membrane proto-oncogene Src family protein tyrosine kinases relay
      growth factor signals to the cytoplasm of mammalian cells. We unravel the spatial
      cycles of solubilisation, trapping on perinuclear membrane compartments and
      vesicular transport that counter entropic equilibration to endomembranes for
      maintaining the enrichment and activity of Src family protein tyrosine kinases at
      the plasma membrane. The solubilising factor UNC119 sequesters myristoylated Src
      family protein tyrosine kinases from the cytoplasm, enhancing their diffusion to
      effectively release Src family protein tyrosine kinases on the recycling endosome
      by localised Arl2/3 activity. Src is then trapped on the recycling endosome via
      electrostatic interactions, whereas Fyn is quickly released to be kinetically
      trapped on the Golgi by palmitoyl acyl-transferase activity. Vesicular
      trafficking from these compartments restores enrichment of the Src family protein
      tyrosine kinases to the plasma membrane. Interference with these spatial cycles
      by UNC119 knockdown disrupts Src family protein tyrosine kinase localisation and
      signalling activity, indicating that UNC119 could be a drug target to affect
      oncogenic Src family protein tyrosine kinase signalling.The peripheral membrane
      proto-oncogene Src family protein tyrosine kinases (SFKs) transmit growth factor
      signals to the cytoplasm. Here the authors show that the solubilising factor
      UNC119 sequesters myristoylated SFKs to maintain its enrichment at the plasma
      membrane to enable signal transduction.

PMID- 28740134
TI  - Programmable base editing of zebrafish genome using a modified CRISPR-Cas9
      system.
AB  - Precise genetic modifications in model animals are essential for biomedical
      research. Here, we report a programmable "base editing" system to induce precise
      base conversion with high efficiency in zebrafish. Using cytidine deaminase fused
      to Cas9 nickase, up to 28% of site-specific single-base mutations are achieved in
      multiple gene loci. In addition, an engineered Cas9-VQR variant with 5'-NGA PAM
      specificities is used to induce base conversion in zebrafish. This shows that
      Cas9 variants can be used to expand the utility of this technology. Collectively,
      the targeted base editing system represents a strategy for precise and effective
      genome editing in zebrafish.The use of base editing enables precise genetic
      modifications in model animals. Here the authors show high efficient single-base
      editing in zebrafish using modified Cas9 and its VQR variant with an altered PAM
      specificity.

PMID- 28740135
TI  - Establishing a yeast-based screening system for discovery of human GLUT5
      inhibitors and activators.
AB  - Human GLUT5 is a fructose-specific transporter in the glucose transporter family
      (GLUT, SLC2 gene family). Its substrate-specificity and tissue-specific
      expression make it a promising target for treatment of diabetes, metabolic
      syndrome and cancer, but few GLUT5 inhibitors are known. To identify and
      characterize potential GLUT5 ligands, we developed a whole-cell system based on a
      yeast strain deficient in fructose uptake, in which GLUT5 transport activity is
      associated with cell growth in fructose-based media or assayed by fructose uptake
      in whole cells. The former method is convenient for high-throughput screening of
      potential GLUT5 inhibitors and activators, while the latter enables detailed
      kinetic characterization of identified GLUT5 ligands. We show that functional
      expression of GLUT5 in yeast requires mutations at specific positions of the
      transporter sequence. The mutated proteins exhibit kinetic properties similar to
      the wild-type transporter and are inhibited by established GLUT5 inhibitors N-[4
      (methylsulfonyl)-2-nitrophenyl]-1,3-benzodioxol-5-amine (MSNBA) and (-)
      epicatechin-gallate (ECG). Thus, this system has the potential to greatly
      accelerate the discovery of compounds that modulate the fructose transport
      activity of GLUT5.

PMID- 28740136
TI  - Anomalous random telegraph noise in nanoscale transistors as direct evidence of
      two metastable states of oxide traps.
AB  - In this paper, a new pattern of anomalous random telegraph noise (RTN), named
      "reversal RTN" (rRTN) induced by single oxide trap, is observed in the drain
      current of nanoscale metal-oxide-semiconductor field-effect transistors (MOSFETs)
      with high-k gate dielectrics. Under each gate voltage, the rRTN data exhibit two
      zones with identical amplitudes but reversal time constants. This abnormal
      switching behavior can be explained by the theory of complete 4-state trap model
      (with two stable states and two metastable states), rather than the simple 2
      state or improved 3-state trap model. The results provide a direct experimental
      evidence of the existence of two metastable states in a single oxide trap,
      contributing to the comprehensive understanding of trap-related reliability and
      variability issues in nanoscale transistors.

PMID- 28740138
TI  - Alantolactone induces apoptosis, promotes STAT3 glutathionylation and enhances
      chemosensitivity of A549 lung adenocarcinoma cells to doxorubicin via oxidative
      stress.
AB  - Alantolactone (ALT), a sesquiterpene lactone component of Inula helenium, has
      been reported to exert anticancer activity in various cancers. However, the
      cellular targets and underlying mechanism of anticancer activity of ALT in
      various cancers including lung cancer has not been fully defined. In the present
      study, we found that ALT effectively inhibits proliferation and triggers
      oxidative stress mediated-apoptosis in A549 lung adenocarcinoma cells by inducing
      ER stress and mitochondrial dysfunction. This ALT-mediated apoptosis was
      inhibited by NAC while diamide potentiated it. Moreover, ALT effectively
      suppressed both constitutive and inducible STAT3 activation, inhibited its
      translocation into nucleus and decreased its DNA binding activity. Further
      mechanistic study revealed that ALT abrogated STAT3 activation by promoting STAT3
      glutathionylation. ROS scavenger NAC reverted ALT-mediated STAT3
      glutathionylation and inhibition of STAT3 phosphorylation. Finally, ALT enhanced
      chemosensitivity of A549 cells to doxorubicin and reversed doxorubicin resistance
      in A549/DR cells by inhibiting STAT3 activation and P-glycoprotein expression and
      increasing intracellular accumulation of doxorubicin. Suppression of STAT3
      activation by targeting ROS metabolism with ALT thus discloses a previously
      unrecognized mechanism underlying the biological activity of ALT. Taken together;
      ALT induces oxidative stress-dependent apoptosis, inhibits STAT3 activation and
      augments doxorubicin toxicity in A549 lung cancer cells. These findings provide
      an in-depth insight into the molecular mechanism of ALT in the treatment of lung
      cancer.

PMID- 28740137
TI  - Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei
      and Burkholderia mallei lipopolysaccharide O-antigens.
AB  - Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents
      of melioidosis and glanders, respectively, cause severe disease in both humans
      and animals. Studies have highlighted the importance of Bp and Bm
      lipopolysaccharides (LPS) as vaccine candidates. Here we describe the synthesis
      of seven oligosaccharides as the minimal structures featuring all of the reported
      acetylation/methylation patterns associated with Bp and Bm LPS O-antigens (OAgs).
      Our approach is based on the conversion of an L-rhamnose into a 6-deoxy-L-talose
      residue at a late stage of the synthetic sequence. Using biochemical and
      biophysical methods, we demonstrate the binding of several Bp and Bm LPS-specific
      monoclonal antibodies with terminal OAg residues. Mice immunized with terminal
      disaccharide-CRM197 constructs produced high-titer antibody responses that
      crossreacted with Bm-like OAgs. Collectively, these studies serve as foundation
      for the development of novel therapeutics, diagnostics, and vaccine candidates to
      combat diseases caused by Bp and Bm.Melioidosis and glanders are multifaceted
      infections caused by gram-negative bacteria. Here, the authors synthesize a
      series of oligosaccharides that mimic the lipopolysaccharides present on the
      pathogens' surface and use them to develop novel glycoconjugates for vaccine
      development.

PMID- 28740139
TI  - Ecologically relevant levels of multiple, common marine stressors suggest
      antagonistic effects.
AB  - Stressors associated with global change will be experienced simultaneously and
      may act synergistically, so attempts to estimate the capacity of marine systems
      to cope with global change requires a multi-stressor approach. Because recent
      evidence suggests that stressor effects can be context-dependent, estimates of
      how stressors are experienced in ecologically realistic settings will be
      particularly valuable. To enhance our understanding of the interplay between
      environmental effects and the impact of multiple stressors from both natural and
      anthropogenic sources, we conducted a field experiment. We explored the impact of
      multiple, functionally varied stressors from both natural and anthropogenic
      sources experienced during early life history in a common sessile marine
      invertebrate, Bugula neritina. Natural spatial environmental variation induced
      differences in conspecific densities, allowing us to test for density-driven
      context-dependence of stressor effects. We indeed found density-dependent
      effects. Under high conspecific density, individual survival increased, which
      offset part of the negative effects of experiencing stressors. Experiencing
      multiple stressors early in life history translated to a decreased survival in
      the field, albeit the effects were not as drastic as we expected: our results are
      congruent with antagonistic stressor effects. We speculate that when individual
      stressors are more subtle, stressor synergies become less common.

PMID- 28740140
TI  - Vulnerability of mixotrophic algae to nutrient pulses and UVR in an oligotrophic
      Southern and Northern Hemisphere lake.
AB  - Nutrient inputs and ultraviolet radiation (UVR) are global factors affecting the
      structure and functioning of aquatic ecosystems, particularly clear-water
      ecosystems. We performed experiments in two model lakes highly exposed to UVR
      fluxes in order to test the effect that future increases in mineral nutrients
      transported by dust aerosol might exert on primary producers depending on the
      likelihood of atmospheric inputs. Lake La Caldera (Northern Hemisphere) has been
      receiving recurrent dust inputs from the Sahara Desert while lake Los Cantaros
      (Southern Hemisphere) has been less affected by dust aerosol. UVR * Nutrient
      synergistically stimulated primary production (PP), chlorophyll a (Chl a), with a
      smaller increase in phytoplanktonic biomass in La Caldera, but not in Los
      Cantaros, where nutrient addition unmasked the UVR inhibitory effect on
      phytoplankton. The proportional decrease of mixotrophic nanoflagellates (MNFs)
      after the nutrient pulse (in Los Cantaros) and the long-term decline of MNFs in
      La Caldera associated with the increase in aerosol-dust intrusions from the
      Sahara during the last 40 years suggest that a future scenario of intensified
      aerosol events from desert and desertified areas would not only reduce functional
      diversity with the decline of MNFs, but would ultimately alter the C flux towards
      the grazing chain in oligotrophic ecosystems.

PMID- 28740141
TI  - An optogenetic toolbox for unbiased discovery of functionally connected cells in
      neural circuits.
AB  - Optical imaging approaches have revolutionized our ability to monitor neural
      network dynamics, but by themselves are unable to link a neuron's activity to its
      functional connectivity. We present a versatile genetic toolbox, termed
      'Optobow', for all-optical discovery of excitatory connections in vivo. By
      combining the Gal4-UAS system with Cre/lox recombination, we target the
      optogenetic actuator ChrimsonR and the sensor GCaMP6 to stochastically labeled,
      nonoverlapping and sparse subsets of neurons. Photostimulation of single cells
      using two-photon computer-generated holography evokes calcium responses in
      downstream neurons. Morphological reconstruction of neurite arbors, response
      latencies and localization of presynaptic markers suggest that some neuron pairs
      recorded here are directly connected, while others are two or more synapses apart
      from each other. With this toolbox, we discover wiring principles between
      specific cell types in the larval zebrafish tectum. Optobow should be useful for
      identification and manipulation of networks of interconnected neurons, even in
      dense neural tissues.Mechanisms of neural processing can only be understood by
      revealing patterns of connectivity among the cellular components of the circuit.
      Here the authors report a new genetic toolbox, 'Optobow', which enables
      simultaneous optogenetic activation of single neurons in zebrafish and measuring
      the activity of downstream neurons in the network.

PMID- 28740142
TI  - Intended outcome expands in time.
AB  - Intentional agents desire specific outcomes and perform actions to obtain those
      outcomes. However, whether getting such desired (intended) outcomes change our
      subjective experience of the duration of that outcome is unknown. Using a
      temporal bisection task, we investigated the changes in temporal perception of
      the outcome as a function of whether it was intended or not. Before each trial,
      participants intended to see one of two possible outcomes but received the
      intended outcome only in half of the trials. Results showed that intended
      outcomes were perceived as longer than unintended outcomes. Interestingly, this
      temporal expansion was present only when the intended outcome appeared after
      short action-outcome delays (250 ms-Exp 1 and 500 ms-Exp 2), but not when it
      appeared after long action-outcome delay (1000 ms-Exp 3). The effect was absent
      when participants did not intend and performed instruction-based action (Exp 4).
      Finally, Exp 5 (verbal estimation task) revealed that intention induced temporal
      expansion occurs via altering the gating or switch mechanism and not the
      pacemaker speed. Results are explained based on intention-induced pre-activation
      resulting in extended temporal experience. Our study not only suggests inclusion
      of intention as a potential factor influencing time perception but also indicates
      a close link between intentional binding and the intention induced temporal
      expansion of its outcome.

PMID- 28740144
TI  - Search for non-lactam inhibitors of mtb beta-lactamase led to its open shape in
      apo state: new concept for antibiotic design.
AB  - Mtb beta-lactamase (BlaC) is extremely efficient in hydrolyzing beta-lactam
      antibiotics which renders/leads to protection and/or resistance to this bug.
      There is a compelling need to develop new non-lactam inhibitors which can bind
      and inhibit BlaC, but cannot be hydrolyzed, thus neutralizing this survival
      mechanism of Mtb. Using the crystal structure of BlaC we screened 750000
      purchasable compounds from ZINC Database for their theoretical affinity to the
      enzyme's active site. 32 of the best hits of the compounds having tetra-, tri-
      and thiadi-azole moiety were tested in vitro, and 4 efficiently inhibited the
      enzymatic activity of recombinant BlaC. Characterization of the shape of BlaC-/+
      inhibitors by small angle X-ray scattering (SAXS) brought forth that BlaC adopts:
      (1) an open shape (radius of gyration of 2.3 nm compared to 1.9 nm of crystal
      structures) in solution; (2) closed shape similar to observed crystal
      structure(s) in presence of effective inhibitor; and (3) a closed shape which
      opens up when a hydrolysable inhibitor is present in solution. New BlaC
      inhibitors were: 1-(4-(pyridin-3-yl)-thiazol-2-ylamino)-2-(7,8,9-triaza
      bicyclo[4.3.0]nona-1(6),2,4,8-tetraen-7-yl)-ethanone; 8-butyl-3-((5-(pyridin-2
      yl)-4H-1,2,4-triazol-3-ylamino)-formyl)-8-aza-bicyclo[4.3.0]nona-1(6),2,4-triene
      7,9-dione; 1-(3-((5-(5-bromo-thiophen-2-yl)-1,3,4-oxadiazol-2-yl)-methoxy)
      phenyl)-1H-1,2,3,4-tetraazole; and 1-(2,3-dimethyl-phenylamino)-2-(2-(1-(2
      methoxy-5-methyl-phenyl)-1H-1,2,3,4-tetraazol-5-ylsulfanyl)-acetylamino)
      ethanone. The open-close shape of BlaC questions the physiological significance
      of the closed shape known for BlaC-/+ inhibitors and paves new path for structure
      aided design of novel inhibitors.

PMID- 28740143
TI  - Downregulation of ALAS1 by nicarbazin treatment underlies the reduced synthesis
      of protoporphyrin IX in shell gland of laying hens.
AB  - Shell colour is an important trait for eggs and an understanding of pigment
      deposition will assist potential management of egg shell colour loss. We
      demonstrated that nicarbazin feeding down-regulated ALAS1 and reduced
      protoporphyrin IX (PP IX) in both shell gland and eggshell, indicating the role
      of nicarbazin in inhibiting the synthesis of PP IX. Additionally, the expression
      levels of the genes did not show sequential upregulation in the same order of
      diurnal time-points (TP) during egg formation. The gene SLC25A38, responsible for
      transporting glycine from cytoplasm to mitochondria, and the gene ALAS1, encoding
      rate-limiting enzyme (delta-aminolevulinic acid synthase 1), had higher
      expression at 15 hr, as compared with 2, 5 and 23.5 hrs postoviposition.
      Interestingly, ABCB6, a gene encoding an enzyme responsible for transporting
      coproporphyrinogen III, showed higher expression level at 2 and 5 hrs. However,
      the expression of CPOX that converts coproporphyrinogen III to protoporphyrinogen
      III, and ABCG2 that transports PP IX out from mitochondria did not alter.
      Nevertheless, mitochondrial count per cell did not show consistent change in
      response to time-points postoviposition and nicarbazin feeding. The information
      obtained in the study sheds light on how nicarbazin disrupts the synthesis of PP
      IX.

PMID- 28740145
TI  - Validation of asynchronous quantitative bone densitometry of the spine: Accuracy,
      short-term reproducibility, and a comparison with conventional quantitative
      computed tomography.
AB  - Asynchronous calibration quantitative computed tomography (QCT) is a new tool
      that allows the quantification of bone mineral density (BMD) without the use of a
      calibration phantom during scanning; however, this tool is not fully validated
      for clinical use. We used the European spine phantom (ESP) with repositioning
      during scanning and assessed the accuracy and short-term reproducibility of
      asynchronous QCT. Intra-scanner and intra-observer precision were each calculated
      as the root mean square of the standard deviation (RMSSD) and the coefficient of
      variation (CV-RMSSD). We also compared asynchronous and conventional QCT results
      in 50 clinical subjects. The accuracy of asynchronous QCT for three ESP vertebrae
      ranged from 1.4-6.7%, whereas intra-scanner precision for these vertebrae ranged
      from 0.53-0.91 mg/cc. Asynchronous QCT was most precise for a trabecular BMD of
      100 mg/cc (CV-RMSSD = 0.2%). For intra-observer variability, overall precision
      error was smaller than 3%. In clinical subjects there was excellent agreement
      between the two calibration methods with correlation coefficients ranging from
      0.96-0.99. A Bland-Altman analysis demonstrated that methodological differences
      depended on the magnitude of the BMD variable. Our findings indicate that the
      asynchronous QCT has good accuracy and precision for assessing trabecular BMD in
      the spine.

PMID- 28740146
TI  - In vivo imaging to monitor differentiation and therapeutic effects of
      transplanted mesenchymal stem cells in myocardial infarction.
AB  - Here, we used a noninvasive multimodality imaging approach to monitor
      differentiation of transplanted bone marrow mesenchymal stem cells (BMSCs) and
      recovery of cardiac function in an in vivo model of myocardial infarction (MI).
      We established a rat MI model by coronary artery ligation. Ninety rats were
      randomly assigned into four groups: sham-operated, MI model, and alpha-MHC-HSV1
      tk-transfected or un-transfected BMSCs-treated MI model. We used 18F-Fluro
      deoxyglucose (18F-FDG) positron emission tomography (PET) to monitor recovery of
      cardiac function, and 18F-FHBG PET/CT imaging to monitor transplanted BMSCs
      differentiation 24 h after 18F-FDG imaging. The uptake of 18F-FDG at 3, 16, 30
      and 45 days after BMSCs injection was 0.39 +/- 0.03, 0.57 +/- 0.05, 0.59 +/-
      0.04, and 0.71 +/- 0.05% ID/g, respectively. Uptake of 18F-FHBG increased
      significantly in large areas in the BMSCs-treated group over time. Ex vivo
      experiments indicated that expression of the cardiomyocyte markers GATA-4 and
      cardiac troponin I markedly increased in the BMSCs-treated group. Additionally,
      immunohistochemistry revealed that HSV-tk-labelled BMSCs-derived cells were
      positive for cardiac troponin I. Multimodal imaging systems combining an alpha
      MHC-HSV1-tk/18F-FHBG reporter gene and 18F-FDG metabolism imaging could be used
      to track differentiation of transplanted BMSCs and recovery of cardiac function
      in MI.

PMID- 28740147
TI  - Recent Warming and Cooling in the Antarctic Peninsula Region has Rapid and Large
      Effects on Lichen Vegetation.
AB  - The Antarctic Peninsula has had a globally large increase in mean annual
      temperature from the 1951 to 1998 followed by a decline that still continues. The
      challenge is now to unveil whether these recent, complex and somewhat unexpected
      climatic changes are biologically relevant. We were able to do this by
      determining the growth of six lichen species on recently deglaciated surfaces
      over the last 24 years. Between 1991 and 2002, when mean summer temperature (MST)
      rose by 0.42  degrees C, five of the six species responded with increased growth.
      MST declined by 0.58  degrees C between 2002 and 2015 with most species showing a
      fall in growth rate and two of which showed a collapse with the loss of large
      individuals due to a combination of increased snow fall and longer snow cover
      duration. Increased precipitation can, counter-intuitively, have major negative
      effects when it falls as snow at cooler temperatures. The recent Antarctic
      cooling is having easily detectable and deleterious impacts on slow growing and
      highly stress-tolerant crustose lichens, which are comparable in extent and
      dynamics, and reverses the gains observed over the previous decades of
      exceptional warming.

PMID- 28740148
TI  - Incremental benefit of late gadolinium cardiac magnetic resonance imaging for
      risk stratification in patients with hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) has a low risk for sudden cardiac death (SCD).
      The ESC clinical risk prediction model estimates the risk of SCD using clinical
      and echocardiographical parameters without taking into account cardiac magnetic
      resonance (CMR) parameters. Therefore, we compared the CMR characteristics of 149
      patients with low, intermediate and high ESC risk scores. In these patients left
      and right ventricular ejection fraction and volumes were comparable. Patients
      with a high ESC risk score revealed a significantly higher extent of late
      gadolinium enhancement (LGE) compared to patients with intermediate or a low risk
      scores. During follow-up of 4 years an extent of LGE >=20% identified patients at
      a higher risk for major adverse cardiac arrhythmic events in the low and
      intermediate ESC risk group whereas an extent of LGE <20% was associated with a
      low risk of major adverse cardiac arrhythmic events despite a high ESC risk score
      >=6%. Hence, we hypothesize that the extent of fibrosis might be an additional
      risk marker.

PMID- 28740149
TI  - Specific effect of a dopamine partial agonist on counterfactual learning:
      evidence from Gilles de la Tourette syndrome.
AB  - The dopamine partial agonist aripiprazole is increasingly used to treat
      pathologies for which other antipsychotics are indicated because it displays
      fewer side effects, such as sedation and depression-like symptoms, than other
      dopamine receptor antagonists. Previously, we showed that aripiprazole may
      protect motivational function by preserving reinforcement-related signals used to
      sustain reward-maximization. However, the effect of aripiprazole on more
      cognitive facets of human reinforcement learning, such as learning from the
      forgone outcomes of alternative courses of action (i.e., counterfactual
      learning), is unknown. To test the influence of aripiprazole on counterfactual
      learning, we administered a reinforcement learning task that involves both direct
      learning from obtained outcomes and indirect learning from forgone outcomes to
      two groups of Gilles de la Tourette (GTS) patients, one consisting of patients
      who were completely unmedicated and the other consisting of patients who were
      receiving aripiprazole monotherapy, and to healthy subjects. We found that
      whereas learning performance improved in the presence of counterfactual feedback
      in both healthy controls and unmedicated GTS patients, this was not the case in
      aripiprazole-medicated GTS patients. Our results suggest that whereas
      aripiprazole preserves direct learning of action-outcome associations, it may
      impair more complex inferential processes, such as counterfactual learning from
      forgone outcomes, in GTS patients treated with this medication.

PMID- 28740150
TI  - Identification of putative unique immunogenic ZIKV and DENV1-4 peptides for
      diagnostic cellular based tests.
AB  - Since the re-emergence of Zika virus in 2014 and subsequent association with
      microcephaly, much work has focused on the development of a vaccine to halt its
      spread throughout the world. The mosquito vector that transmits this virus is
      widespread and responsible for the spread of other arboviridae including Dengue.
      Current diagnostic methods rely on serologic testing that are complicated by
      cross reactivity and therefore unable to distinguish Zika from Dengue infection
      in the absence of virus isolation. We performed an in silico analysis to identify
      potential epitopes that may stimulate a unique T-lymphocyte response to
      distinguish prior infection with Zika or Dengue. From this analysis, we not only
      identified epitopes unique to Zika and Dengue, but also identified epitopes
      unique to each Dengue serotype. These peptides contribute to a pool of peptides
      identified for vaccine development that can be tested in vitro to confirm
      immunogenicity, absence of homology and global population coverage. The current
      lack of accurate diagnostic testing hampers our ability to understand the scope
      of the epidemic, implications for vaccine implementation and complications
      related to monoinfection and co-infection with these two closely related viruses.

PMID- 28740151
TI  - Critical behaviour in the optimal generation of multipartite entanglement.
AB  - Two systems whose correlations cannot be classically accounted for display the
      simplest instance of quantum entanglement. Although this two-party association
      has caused a revolution in the foundations and uses of quantum mechanics, genuine
      entanglement among several parties unveils a whole new class of phenomena and
      applications. In this work we suggest a way to prepare Dicke states from a
      tunable source of bipartite entanglement to investigate foundational issues. The
      scheme has the following distinctive features: (i) it relies on controlled
      information loss and unentangled measurements; (ii) irrespective of the source
      entanglement, whenever a Dicke state is produced, it is ideal; (iii) the optimal
      entanglement of the bipartite source undergoes a second-order-like transition
      depending on the parameters of the Dicke state to be produced. These properties
      lead to asymptotic results on the entanglement between any qubit belonging to a
      Dicke state and the remaining qubits.

PMID- 28740152
TI  - A cell-based, quantitative and isoform-specific assay for exchange proteins
      directly activated by cAMP.
AB  - Extensive functional studies of the exchange protein directly activated by cAMP
      (EPAC) family of signaling molecules have demonstrated that EPAC proteins play a
      fundamental role in several physiological and pathophysiological responses,
      therefore are attractive drug targets. In this report, the development of a cell
      based, medium to high throughput screening assay that is capable of monitoring
      EPAC-mediated activation of cellular Rap1 in an isoform-specific manner is
      described. This assay adapts a conventional ELISA format with immobilized RalGDS
      RBD as a bait to selectively capture GTP-bound active Rap1. As a result, it fills
      an urgent need for a cell-based EPAC assay that can be conveniently performed
      using microtiter plates for the discovery and/or validation of isoform-specific
      EPAC agonists and antagonists.

PMID- 28740153
TI  - Continuous and scalable polymer capsule processing for inertial fusion energy
      target shell fabrication using droplet microfluidics.
AB  - High specification, polymer capsules, to produce inertial fusion energy targets,
      were continuously fabricated using surfactant-free, inertial centralisation, and
      ultrafast polymerisation, in a scalable flow reactor. Laser-driven, inertial
      confinement fusion depends upon the interaction of high-energy lasers and
      hydrogen isotopes, contained within small, spherical and concentric target
      shells, causing a nuclear fusion reaction at ~150 M degrees C. Potentially,
      targets will be consumed at ~1 M per day per reactor, demanding a 5000x unit cost
      reduction to ~$0.20, and is a critical, key challenge. Experimentally, double
      emulsions were used as templates for capsule-shells, and were formed at 20 Hz, on
      a fluidic chip. Droplets were centralised in a dynamic flow, and their shapes
      both evaluated, and mathematically modeled, before subsequent shell
      solidification. The shells were photo-cured individually, on-the-fly, with
      precisely-actuated, millisecond-length (70 ms), uniform-intensity UV pulses,
      delivered through eight, radially orchestrated light-pipes. The near 100% yield
      rate of uniform shells had a minimum 99.0% concentricity and sphericity, and the
      solidification processing period was significantly reduced, over conventional
      batch methods. The data suggest the new possibility of a continuous, on-the-fly,
      IFE target fabrication process, employing sequential processing operations within
      a continuous enclosed duct system, which may include cryogenic fuel-filling, and
      shell curing, to produce ready-to-use IFE targets.

PMID- 28740154
TI  - Ab Initio Density Functional Calculations and Infra-Red Study of CO Interaction
      with Pd Atoms on theta-Al2O3 (010) Surface.
AB  - The ab initio density functional theoretical studies show that energetics favor
      CO oxidation on single Pd atoms supported on theta-alumina. The diffuse
      reflectance infra-red spectroscopy (DRIFTS) results show that carbonates are
      formed as intermediates when single supported Pd atoms are exposed to a gaseous
      mixture of CO + O2. The rapid agglomeration of Pd atoms under CO oxidation
      conditions even at 6  degrees C leads to the presence of Pd particles along with
      single atoms during CO oxidation experiments. Thus, the observed CO oxidation has
      contributions from both single Pd atoms and Pd particles.

PMID- 28740155
TI  - Trajectory of blood pressure change during pregnancy and the role of pre-gravid
      blood pressure: a functional data analysis approach.
AB  - The study aims to examine the blood pressure (BP) trajectory during pregnancy and
      its association with pre-gravid BP level. In a pre-conception cohort study, newly
      married women in Liuyang, China underwent pre-gravid measurements and were
      followed throughout the pregnancy. BP was measured at pre-conception and again
      throughout pregnancy. The functional principal component analysis was used to
      examine the trajectory of BP changes during pregnancy. A total of 1282 women with
      a singleton pregnancy who had both pre-conception and gestational BP measurements
      performed were included in the final analysis. The results showed that BP
      decreased significantly in early pregnancy and increased thereafter, without BP
      drop around 20 weeks of gestation. Pre-gravid BP level was inversely associated
      with the BP drop in early pregnancy, such that women with higher pre-gravid BP
      had greater BP drop at the beginning, while women with the lowest pre-gravid BP
      level demonstrated no obvious BP drop throughout the entire pregnancy.

PMID- 28740156
TI  - Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape.
AB  - The distribution of the transcription machinery among different sub-nuclear
      domains raises the question on how the architecture of the nucleus modulates the
      transcriptional response. Here, we used fluorescence fluctuation analyses to
      quantitatively explore the organization of the glucocorticoid receptor (GR) in
      the interphase nucleus of living cells. We found that this ligand-activated
      transcription factor diffuses within the nucleus and dynamically interacts with
      bodies enriched in the coregulator NCoA-2, DNA-dependent foci and chromatin
      targets. The distribution of the receptor among the nuclear compartments depends
      on NCoA-2 and the conformation of the receptor as assessed with synthetic ligands
      and GR mutants with impaired transcriptional abilities. Our results suggest that
      the partition of the receptor in different nuclear reservoirs ultimately
      regulates the concentration of receptor available for the interaction with
      specific targets, and thus has an impact on transcription regulation.

PMID- 28740157
TI  - Potentiation of 17beta-estradiol synthesis in the brain and elongation of seizure
      latency through dietary supplementation with docosahexaenoic acid.
AB  - Several studies have shown that docosahexaenoic acid (DHA) attenuates epileptic
      seizures; however, the molecular mechanism by which it achieves this effect is
      still largely unknown. DHA stimulates the retinoid X receptor, which reportedly
      regulates the expression of cytochrome P450 aromatase (P450arom). This study
      aimed to clarify how DHA suppresses seizures, focusing on the regulation of
      17beta-estradiol synthesis in the brain. Dietary supplementation with DHA
      increased not only the expression of P450arom, but also 17beta-estradiol in the
      cerebral cortex. While DHA did not affect the duration or scores of the seizures
      induced by pentylenetetrazole, DHA significantly prolonged the seizure latency. A
      P450arom inhibitor, letrozole, reduced 17beta-estradiol levels and completely
      suppressed the elongation of seizure latency elicited by DHA. These results
      suggest that DHA delays the onset of seizures by promoting the synthesis of
      17beta-estradiol in the brain. DHA upregulated the expression of anti-oxidative
      enzymes in the cerebral cortex. The oxidation in the cerebral cortex induced by
      pentylenetetrazole was significantly attenuated by DHA, and letrozole completely
      inhibited this suppressive action. Thus, the anti-oxidative effects of 17beta
      estradiol may be involved in the prevention of seizures mediated by DHA. This
      study revealed that 17beta-estradiol in the brain mediated the physiological
      actions of DHA.

PMID- 28740158
TI  - Bayesian Network analysis of piglet scours.
AB  - Diarrhoeal disease (scours) in piglets, often associated with enterotoxigenic
      Escherichia coli (ETEC), is a substantial financial burden to the pig industry
      worldwide. Previous research has not explicitly examined the relationships
      between farm, pen and microbiological factors. Here we present a state of the art
      analysis to reveal empirical indirect - as well as direct - associations between
      management factors as putative risks for scours in pre- and post-weaned piglets.
      A Bayesian Network is constructed to identify the optimal structural model
      describing the relationships between risk factors. An additive model is then
      built to estimate more epidemiologically familiar odds ratios. Farm-level
      variance dominates the model, making many pen-level associations null. However,
      there is evidence that pre-weaning scours are less likely on farms with <400 sows
      (0.14, 0.03-0.50). Our results strongly suggest that smaller production units
      (piglets/pen) could reduce the incidence of scours in piglets. There is also some
      evidence that ownership of other livestock is a potential risk factor for pre
      weaning scours, although this was observed only at one farm. Future research
      should be directed at better understanding the role of herd size and
      investigating the relationship between managing other livestock and the
      occurrence of scours in pig herds.

PMID- 28740159
TI  - Human Zika infection induces a reduction of IFN-gamma producing CD4 T-cells and a
      parallel expansion of effector Vdelta2 T-cells.
AB  - The definition of the immunological response to Zika (ZIKV) infection in humans
      represents a key issue to identify protective profile useful for vaccine
      development and for pathogenesis studies. No data are available on the cellular
      immune response in the acute phase of human ZIKV infection, and its role in the
      protection and/or pathogenesis needs to be clarified. We studied and compared the
      phenotype and functionality of T-cells in patients with acute ZIKV and Dengue
      viral (DENV) infections. A significant activation of T-cells was observed during
      both ZIKV and DENV infections. ZIKV infection was characterized by a CD4 T cell
      differentiation toward effector cells and by a lower frequency of IFN-gamma
      producing CD4 T cells. Moreover, a substantial expansion of CD3+CD4-CD8- T-cell
      subset expressing Vdelta2 TCR was specifically observed in ZIKV patients. Vdelta2
      T cells presented a terminally differentiated profile, expressed granzyme B and
      maintained their ability to produce IFN-gamma. These findings provide new
      knowledge on the immune response profile during self-limited infection that may
      help in vaccine efficacy definition, and in identifying possible immuno
      pathogenetic mechanisms of severe infection.

PMID- 28740160
TI  - Combined atomic force microscopy and photoluminescence imaging to select single
      InAs/GaAs quantum dots for quantum photonic devices.
AB  - We report on a combined photoluminescence imaging and atomic force microscopy
      study of single, isolated self-assembled InAs quantum dots. The motivation of
      this work is to determine an approach that allows to assess single quantum dots
      as candidates for quantum nanophotonic devices. By combining optical and scanning
      probe characterization techniques, we find that single quantum dots often appear
      in the vicinity of comparatively large topographic features. Despite this, the
      quantum dots generally do not exhibit significant differences in their non
      resonantly pumped emission spectra in comparison to quantum dots appearing in
      defect-free regions, and this behavior is observed across multiple wafers
      produced in different growth chambers. Such large surface features are
      nevertheless a detriment to applications in which single quantum dots are
      embedded within nanofabricated photonic devices: they are likely to cause large
      spectral shifts in the wavelength of cavity modes designed to resonantly enhance
      the quantum dot emission, thereby resulting in a nominally perfectly-fabricated
      single quantum dot device failing to behave in accordance with design. We
      anticipate that the approach of screening quantum dots not only based on their
      optical properties, but also their surrounding surface topographies, will be
      necessary to improve the yield of single quantum dot nanophotonic devices.

PMID- 28740161
TI  - Optimization-based design of heat flux manipulation devices with emphasis on
      fabricability.
AB  - In this work, we present a new method for the design of heat flux manipulating
      devices, with emphasis on their fabricability. The design is obtained as solution
      of a nonlinear optimization problem where the objective function represents the
      given heat flux manipulation task, and the design variables define the material
      distribution in the device. In order to facilitate the fabrication of the device,
      the material at a given point is chosen from a set of predefined metamaterials.
      Each candidate material is assumed to be a laminate of materials with high
      conductivity contrast, so it is a metamaterial with a highly anisotropic
      effective conductivity. Following the discrete material optimization (DMO)
      approach, the fraction of each material at a given finite element of the mesh is
      defined as a function of continuous variables, which are ultimately the design
      variables. This DMO definition forces the fraction of each candidate to tend to
      either zero or one at the optimal solution. As an application example, we
      designed an easy-to-make device for heat flux concentration and cloaking.

PMID- 28740162
TI  - Nomogram predicted risk of peripherally inserted central catheter related
      thrombosis.
AB  - The use of peripherally inserted central catheters (PICCs) is increasing rapidly
      worldwide. A number of patient-related, clinical-related and device-related
      characteristics might be risk factors for PICC-related thrombosis. We
      retrospectively reviewed a database of 320 consecutive patients who underwent
      PICC insertion between December 2014 and December 2015 at the First Affiliated
      Hospital of Xi'an Jiaotong University to explore the potential associations
      between risk factors and PICC-associated thrombosis. A novel nomogram for
      predicting risk was developed based on the data. The nomogram prediction model
      included ten risk factors that were derived from different relevant estimates.
      The nomogram prediction model showed good discriminatory power (Harrell's C
      index, 0.709) and a high degree of similarity to actual thrombosis occurring
      after calibration. Furthermore, principal component analysis was performed to
      identify the factors that most influence PICC-related thrombosis. Our novel
      nomogram thrombosis risk prediction model was accurate in predicting PICC-related
      thrombosis. Karnofsky performance scores, D-dimer and blood platelet levels and
      previous chemotherapy were principal components. Our findings might help
      clinicians predict thrombosis risk in individual patients, select proper
      therapeutic strategies and optimize the timing of anticoagulation therapy.

PMID- 28740163
TI  - Determination of the Solid Electrolyte Interphase Structure Grown on a Silicon
      Electrode Using a Fluoroethylene Carbonate Additive.
AB  - In this work we explore how an electrolyte additive (fluorinated ethylene
      carbonate - FEC) mediates the thickness and composition of the solid electrolyte
      interphase formed over a silicon anode in situ as a function of state-of-charge
      and cycle. We show the FEC condenses on the surface at open circuit voltage then
      is reduced to C-O containing polymeric species around 0.9 V (vs. Li/Li+). The
      resulting film is about 50 A thick. Upon lithiation the SEI thickens to 70 A and
      becomes more organic-like. With delithiation the SEI thins by 13 A and becomes
      more inorganic in nature, consistent with the formation of LiF. This
      thickening/thinning is reversible with cycling and shows the SEI is a dynamic
      structure. We compare the SEI chemistry and thickness to 280 A thick SEI layers
      produced without FEC and provide a mechanism for SEI formation using FEC
      additives.

PMID- 28740164
TI  - Raised-Volume Forced Expiratory Flow-Volume Curve in Healthy Taiwanese Infants.
AB  - The raised-volume rapid thoracoabdominal compression (RVRTC) manoeuvre has been
      applied to obtain full forced expiratory flow-volume curves in infants. No
      reference data are available for Asian populations. This study was conducted to
      establish predictive reference equations for Taiwanese infants. Full-term infants
      without any chronic disease or major anomaly were enrolled from this cohort
      study. Full forced expiratory flow-volume curves were acquired using RVRTC
      manoeuvres through Jaeger's system. Tidal breath analysis, passive respiratory
      mechanics, and tidal forced expiratory flow-volume curves were performed and
      collected at the same measurement. Multiple linear analyses were used to model
      the variables. We performed 117 tests of RVRTC flow-volume curves in 97 infants.
      The results revealed that all parameters, except for FEV0.5 /FVC, correlated
      highly and positively with body length. These parameters correlated significantly
      with other parameters of passive respiratory mechanics and tidal forced
      expiratory flow-volume curves. This is the first study to establish equipment
      specific reference data of full forced expiration using RVRTC manoeuvres in Asian
      infants. The results revealed that parameters of RVRTC manoeuvres are moderately
      related to other parameters of infant lung function. These race-specific
      reference data can be used to more precisely and efficiently diagnose respiratory
      diseases in infants of Chinese ethnicity.

PMID- 28740165
TI  - Myricetin improves endurance capacity and mitochondrial density by activating
      SIRT1 and PGC-1alpha.
AB  - Robust mitochondrial respiration provides energy to support physical performance
      and physiological well-being, whereas mitochondrial malfunction is associated
      with various pathologies and reduced longevity. In the current study, we tested
      whether myricetin, a natural flavonol with diverse biological activities, may
      impact mitochondrial function and longevity. The mice were orally administered
      myricetin (50 mg/kg/day) for 3 weeks. Myricetin significantly potentiated aerobic
      capacity in mice, as evidenced by their increased running time and distance. The
      elevated mitochondrial function was associated with induction of genes for
      oxidative phosphorylation and mitochondrial biogenesis in metabolically active
      tissues. Importantly, myricetin treatment led to decreased PGC-1alpha acetylation
      through SIRT1 activation. Furthermore, myricetin significantly improved the
      healthspan and lifespan of wild-type, but not Sir-2.1-deficient, C. elegans.
      These results demonstrate that myricetin enhances mitochondrial activity,
      possibly by activating PGC-1alpha and SIRT1, to improve physical endurance,
      strongly suggesting myricetin as a mitochondria-activating agent.

PMID- 28740166
TI  - Studies of global and local entanglements of individual protein chains using the
      concept of knotoids.
AB  - We study here global and local entanglements of open protein chains by
      implementing the concept of knotoids. Knotoids have been introduced in 2012 by
      Vladimir Turaev as a generalization of knots in 3-dimensional space. More
      precisely, knotoids are diagrams representing projections of open curves in 3D
      space, in contrast to knot diagrams which represent projections of closed curves
      in 3D space. The intrinsic difference with classical knot theory is that the
      generalization provided by knotoids admits non-trivial topological entanglement
      of the open curves provided that their geometry is frozen as it is the case for
      crystallized proteins. Consequently, our approach doesn't require the closure of
      chains into loops which implies that the geometry of analysed chains does not
      need to be changed by closure in order to characterize their topology. Our study
      revealed that the knotoid approach detects protein regions that were classified
      earlier as knotted and also new, topologically interesting regions that we
      classify as pre-knotted.

PMID- 28740167
TI  - DNA end resection requires constitutive sumoylation of CtIP by CBX4.
AB  - DNA breaks are complex DNA lesions that can be repaired by two alternative
      mechanisms: non-homologous end-joining and homologous recombination. The decision
      between them depends on the activation of the DNA resection machinery, which
      blocks non-homologous end-joining and stimulates recombination. On the other
      hand, post-translational modifications play a critical role in DNA repair. We
      have found that the SUMO E3 ligase CBX4 controls resection through the key factor
      CtIP. Indeed, CBX4 depletion impairs CtIP constitutive sumoylation and DNA end
      processing. Importantly, mutating lysine 896 in CtIP recapitulates the CBX4
      depletion phenotype, blocks homologous recombination and increases genomic
      instability. Artificial fusion of CtIP and SUMO suppresses the effects of both
      the non-sumoylatable CtIP mutant and CBX4 depletion. Mechanistically, CtIP
      sumoylation is essential for its recruitment to damaged DNA. In summary,
      sumoylation of CtIP at lysine 896 defines a subpopulation of the protein that is
      involved in DNA resection and recombination.The choice between non-homologous end
      joining and homologous recombination to repair a DNA double-strand break depends
      on activation of the end resection machinery. Here the authors show that SUMO E3
      ligase CBX4 sumoylates subpopulation of CtIP to regulate recruitment to breaks
      and resection.

PMID- 28740168
TI  - Compounding Impacts of Human-Induced Water Stress and Climate Change on Water
      Availability.
AB  - The terrestrial phase of the water cycle can be seriously impacted by water
      management and human water use behavior (e.g., reservoir operation, and
      irrigation withdrawals). Here we outline a method for assessing water
      availability in a changing climate, while explicitly considering anthropogenic
      water demand scenarios and water supply infrastructure designed to cope with
      climatic extremes. The framework brings a top-down and bottom-up approach to
      provide localized water assessment based on local water supply infrastructure and
      projected water demands. When our framework is applied to southeastern Australia
      we find that, for some combinations of climatic change and water demand, the
      region could experience water stress similar or worse than the epic Millennium
      Drought. We show considering only the influence of future climate on water
      supply, and neglecting future changes in water demand and water storage
      augmentation might lead to opposing perspectives on future water availability.
      While human water use can significantly exacerbate climate change impacts on
      water availability, if managed well, it allows societies to react and adapt to a
      changing climate. The methodology we present offers a unique avenue for linking
      climatic and hydrologic processes to water resource supply and demand management
      and other human interactions.

PMID- 28740169
TI  - Analysis of newly detected tetracycline resistance genes and their flanking
      sequences in human intestinal bifidobacteria.
AB  - Due to tetracycline abuse, the safe bifidobacteria in the human gastrointestinal
      intestinal tract (GIT) may serve as a reservoir of tetracycline resistance genes.
      In the present investigation of 92 bifidobacterial strains originating from the
      human GIT, tetracycline resistance in 29 strains was mediated by the tet(W),
      tet(O) or tet(S) gene, and this is the first report of tet(O)- and tet(S)
      mediated tetracycline resistance in bifidobacteria. Antibiotic resistance genes
      harbored by bifidobacteria are transferred from other bacteria. However, the
      characteristics of the spread and integration of tetracycline resistance genes
      into the human intestinal bifidobacteria chromosome are poorly understood. Here,
      conserved sequences were identified in bifidobacterial strains positive for
      tet(W), tet(O), or tet(S), including the tet(W), tet(O), or tet(S) and their
      partial flanking sequences, which exhibited identity with the sequences in
      multiple human intestinal pathogens, and genes encoding 23 S rRNA, an ATP
      transporter, a Cpp protein, and a membrane-spanning protein were flanking by the
      1920-bp tet(W), 1920-bp tet(O), 1800-bp tet(O) and 252-bp tet(S) in
      bifidobacteria, respectively. These findings suggest that tetracycline resistance
      genes harbored by human intestinal bifidobacteria might initially be transferred
      from pathogens and that each kind of tetracycline resistance gene might tend to
      insert in the vicinity of specific bifidobacteria genes.

PMID- 28740170
TI  - A GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus modulates
      immune response in macrophages and in mice.
AB  - A GalNAc/Gal-specific lectin (CGL) from the edible mussel Crenomytilus grayanus
      has been demonstrated to exhibit antibacterial properties. However, the mechanism
      of immune modulation by CGL in mammalian cells remains unclear. Here, we
      demonstrated that CGL can activate immune responses in macrophages and in mice.
      In the in vitro cell models, CGL induced tumour necrosis factor-alpha and
      interleukin-6 secretion in mouse RAW264.7 macrophages, mouse bone marrow-derived
      macrophages, human THP-1 macrophages, human peripheral blood mononuclear cells
      and human blood monocyte-derived macrophages. The CGL-mediated cytokine
      production was regulated by reactive oxygen species, mitogen-activated protein
      kinases, protein kinase C-alpha/delta and NF-kappaB. Interestingly, in
      lipopolysaccharide-activated macrophages, CGL induced endotoxin tolerance
      (characterized by the downregulation of nitric oxide, inducible nitric oxide
      synthase, interleukin-6 and cyclooxygenase II) via the downregulation of IRAK2
      expression, JNK1/2 phosphorylation and NF-kappaB activation. CGL also slightly
      increased the bactericidal activity of macrophages and induced cytokine
      production in mouse models. Overall, our data indicate that CGL has the potential
      to be used as an immune modulator in mammals.

PMID- 28740171
TI  - A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and
      beta-amyloid plaques in a triple transgenic mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a degenerative disorder typified by progressive
      deterioration of memory and the appearance of beta-amyloid peptide (Abeta)-rich
      senile plaques. Recently we have identified a novel function of a patented
      formulation of modified Huanglian-Jie-Tu-Tang (HLJDT-M), a Chinese herbal
      medicine, in treating AD in in vitro studies (US patent No. 9,375,457). HLJDT-M
      is a formulation composed of Rhizoma Coptitis, Cortex Phellodendri and Fructus
      Gardeniae without Radix Scutellariae. Here, we assessed the efficacy of HLJDT-M
      on a triple transgenic mouse model of AD (3XTg-AD). Oral administration of HLJDT
      M ameliorated the cognitive dysfunction of 3XTg-AD mice and lessened the plaque
      burden. In addition, biochemical assays revealed a significant decrease in levels
      of detergent-soluble and acid-soluble Abeta via decreasing the levels of full
      length amyloid-beta precursor protein (FL-APP) and C-terminal fragments of APP
      (CTFs) in brain lysates of HLJDT-M-treated mice. HLJDT-M treatment also
      significantly reduced the levels of FL-APP and CTFs in N2a/SweAPP cells. In
      contrast, treatment using the classical formula HLJDT did not reduce the memory
      impairment of 3XTg-AD mice and, rather, increased the Abeta/Fl-APP/CTFs in both
      animal and cell culture studies. Altogether, our study indicates that HLJDT-M is
      a promising herbal formulation to prevent and/or cure AD.

PMID- 28740172
TI  - Bottom-up effects on herbivore-induced plant defences: a case study based on
      compositional patterns of rhizosphere microbial communities.
AB  - Below-ground soil microorganisms can modulate above-ground plant-insect
      interactions. It still needs to be determined whether this is a direct effect of
      single species or an indirect effect of shifts in soil microbial community
      assemblages. Evaluation of the soil microbiome as a whole is critical for
      understanding multi-trophic interactions, including those mediated by volatiles
      involving plants, herbivorous insects, predators/parasitoids and microorganisms.
      We implemented a regulated system comprising Nerium oleander plants grown in soil
      initially containing a sterile/non sterile inoculum, herbivore Aphis nerii and
      predator Chrysoperla carnea. After aphid attack, plants emitted a characteristic
      blend of volatiles derived from two biosynthetic classes: fatty acid catabolites
      and aromatic-derived products. Three aliphatic compounds were mainly detected in
      plants grown in the inoculated microbial soil, a blend which was preferentially
      chosen by C. carnea adult females. The contrasting effect of the initial inocula
      was attributed to the different microbial consortia developed in each treatment.
      We argue that differences in the relative abundance of the active microbial
      communities in the rhizosphere correlate with those in the emission of selected
      volatile compounds by attacked plants. The mechanisms involved in how the
      functional soil microbiome modulates inducible indirect defence of plants are
      discussed.

PMID- 28740173
TI  - Exploring the binding sites and proton diffusion on insulin amyloid fibril
      surfaces by naphthol-based photoacid fluorescence and molecular simulations.
AB  - The diffusion of protons along biological surfaces and the interaction of
      biological structures with water are fundamental areas of interest in biology and
      chemistry. Here, we examine the surface of insulin amyloid fibrils and follow the
      binding of small molecules (photoacids) that differ according to the number and
      location of their sulfonic groups. We use transient fluorescence combined with a
      spherically-symmetric diffusion theory to show that the binding mode of different
      photoacids determines the efficiency of proton dissociation from the photoacid
      and the dimensionality of the proton's diffusion. We use molecular dynamics
      simulations to examine the binding mode and mechanism of the photoacids and its
      influence on the unique kinetic rates and diffusion properties of the photoacid's
      dissociated proton, where we also suggest a proton transfer process between one
      of the photoacids to proximal histidine residues. We show that the photoacids can
      be used as fluorescent markers for following the progression of amyloidogenic
      processes. The detailed characterisation of different binding modes to the
      surface of amyloid fibrils paves the way for better understanding of the binding
      mechanism of small molecules to amyloid fibrils.

PMID- 28740174
TI  - Plakophilin-2 is required for transcription of genes that control calcium cycling
      and cardiac rhythm.
AB  - Plakophilin-2 (PKP2) is a component of the desmosome and known for its role in
      cell-cell adhesion. Mutations in human PKP2 associate with a life-threatening
      arrhythmogenic cardiomyopathy, often of right ventricular predominance. Here, we
      use a range of state-of-the-art methods and a cardiomyocyte-specific, tamoxifen
      activated, PKP2 knockout mouse to demonstrate that in addition to its role in
      cell adhesion, PKP2 is necessary to maintain transcription of genes that control
      intracellular calcium cycling. Lack of PKP2 reduces expression of Ryr2 (coding
      for Ryanodine Receptor 2), Ank2 (coding for Ankyrin-B), Cacna1c (coding for
      CaV1.2) and Trdn (coding for triadin), and protein levels of calsequestrin-2
      (Casq2). These factors combined lead to disruption of intracellular calcium
      homeostasis and isoproterenol-induced arrhythmias that are prevented by
      flecainide treatment. We propose a previously unrecognized arrhythmogenic
      mechanism related to PKP2 expression and suggest that mutations in PKP2 in humans
      may cause life-threatening arrhythmias even in the absence of structural
      disease.It is believed that mutations in desmosomal adhesion complex protein
      plakophilin 2 (PKP2) cause arrhythmia due to loss of cell-cell communication.
      Here the authors show that PKP2 controls the expression of proteins involved in
      calcium cycling in adult mouse hearts, and that lack of PKP2 can cause arrhythmia
      in a structurally normal heart.

PMID- 28740176
TI  - Partial Correlation between Spatial and Temporal Regularities of Human Mobility.
AB  - The regularity of human mobility has been extensively studied because of its
      prominent applications in a considerable number of important areas. Entropy, in
      addition to many other measures, has long been used to quantify the regularity of
      human mobility. We adopt the commonly used spatial entropy and develop an
      analogical temporal entropy to separately investigate the spatial and temporal
      regularities of human mobility. The underlying data are from an automated transit
      fare collection system operated by a metropolitan public transit authority in
      China. The distributions of both spatial and temporal entropies and their
      dependences on several widely used statistics are examined. The spatial and
      temporal entropies present a statistically significant correlation, which has not
      previously been reported to the best of our knowledge.

PMID- 28740175
TI  - Genetic and functional characterization of disease associations explains
      comorbidity.
AB  - Understanding relationships between diseases, such as comorbidities, has
      important socio-economic implications, ranging from clinical study design to
      health care planning. Most studies characterize disease comorbidity using shared
      genetic origins, ignoring pathway-based commonalities between diseases. In this
      study, we define the disease pathways using an interactome-based extension of
      known disease-genes and introduce several measures of functional overlap. The
      analysis reveals 206 significant links among 94 diseases, giving rise to a highly
      clustered disease association network. We observe that around 95% of the links in
      the disease network, though not identified by genetic overlap, are discovered by
      functional overlap. This disease network portraits rheumatoid arthritis, asthma,
      atherosclerosis, pulmonary diseases and Crohn's disease as hubs and thus pointing
      to common inflammatory processes underlying disease pathophysiology. We identify
      several described associations such as the inverse comorbidity relationship
      between Alzheimer's disease and neoplasms. Furthermore, we investigate the
      disruptions in protein interactions by mapping mutations onto the domains
      involved in the interaction, suggesting hypotheses on the causal link between
      diseases. Finally, we provide several proof-of-principle examples in which we
      model the effect of the mutation and the change of the association strength,
      which could explain the observed comorbidity between diseases caused by the same
      genetic alterations.

PMID- 28740177
TI  - Physical access for residue-mineral interactions controls organic carbon
      retention in an Oxisol soil.
AB  - Oxisol soils are widely distributed in the humid tropical and subtropical regions
      and are generally characterized with high contents of metal oxides. High metal
      oxides are believed to facilitate organic carbon (C) accumulation via mineral
      organic C interactions but Oxisols often have low organic C. Yet, the causes that
      constrain organic C accumulation in Oxisol soil are not exactly clear. Here we
      report results from a microcosm experiment that evaluated how the quantity and
      size of crop residue fragments affect soil C retention in a typical Oxisol soil
      in southeast China. We found that there were significantly higher levels of
      dissolved organic C (DOC), microbial biomass C (MBC) and C accumulation in the
      heavy soil fraction in soil amended with fine-sized (<0.2 mm) compared with
      coarse-sized (5.0 mm) fragments. Attenuated total reflectance-Fourier transform
      infrared spectroscopy analysis further showed that fine-sized residues promoted
      stabilization of aliphatic C-H and carboxylic C=O compounds associated with
      mineral phases. In addition, correlation analysis revealed that the increased
      content of organic C in the heavy soil fraction was positively correlated with
      increased DOC and MBC. Together, these results suggest that enhancement of
      contact between organic materials and soil minerals may promote C stabilization
      in Oxisols.

PMID- 28740178
TI  - Angiopoietin-like 4 induces a beta-catenin-mediated upregulation of ID3 in
      fibroblasts to reduce scar collagen expression.
AB  - In adult skin wounds, collagen expression rapidly re-establishes the skin
      barrier, although the resultant scar is aesthetically and functionally inferior
      to unwounded tissue. Although TGFbeta signaling and fibroblasts are known to be
      responsible for scar-associated collagen production, there are currently no
      prophylactic treatments for scar management. Fibroblasts in crosstalk with wound
      keratinocytes orchestrate collagen expression, although the precise paracrine
      pathways involved remain poorly understood. Herein, we showed that the
      matricellular protein, angiopoietin-like 4 (ANGPTL4), accelerated wound closure
      and reduced collagen expression in diabetic and ANGPTL4-knockout mice. Similar
      observations were made in wild-type rat wounds. Using human fibroblasts as a
      preclinical model for mechanistic studies, we systematically elucidated that
      ANGPTL4 binds to cadherin-11, releasing membrane-bound beta-catenin which
      translocate to the nucleus and transcriptionally upregulate the expression of
      Inhibitor of DNA-binding/differentiation protein 3 (ID3). ID3 interacts with
      scleraxis, a basic helix-loop-helix transcription factor, to inhibit scar
      associated collagen types 1alpha2 and 3alpha1 production by fibroblasts. We also
      showed ANGPTL4 interaction with cadherin-11 in human scar tissue. Our findings
      highlight a central role for matricellular proteins such as ANGPTL4 in the
      attenuation of collagen expression and may have a broader implication for other
      fibrotic pathologies.

PMID- 28740179
TI  - Legionella pneumophila infection activates bystander cells differentially by
      bacterial and host cell vesicles.
AB  - Extracellular vesicles from eukaryotic cells and outer membrane vesicles (OMVs)
      released from gram-negative bacteria have been described as mediators of pathogen
      host interaction and intercellular communication. Legionella pneumophila (L.
      pneumophila) is a causative agent of severe pneumonia. The differential effect of
      bacterial and host cell vesicles in L. pneumophila infection is unknown so far.
      We infected THP-1-derived or primary human macrophages with L. pneumophila and
      isolated supernatant vesicles by differential centrifugation. We observed an
      increase of exosomes in the 100 k pellet by nanoparticle tracking analysis,
      electron microscopy, and protein markers. This fraction additionally contained
      Legionella LPS, indicating also the presence of OMVs. In contrast, vesicles in
      the 16 k pellet, representing microparticles, decreased during infection. The 100
      k vesicle fraction activated uninfected primary human alveolar epithelial cells,
      A549 cells, and THP-1 cells. Epithelial cell activation was reduced by exosome
      depletion (anti-CD63, or GW4869), or blocking of IL-1beta in the supernatant. In
      contrast, the response of THP-1 cells to vesicles was reduced by a TLR2
      neutralizing antibody, UV-inactivation of bacteria, or - partially - RNase
      treatment of vesicles. Taken together, we found that during L. pneumophila
      infection, neighbouring epithelial cells were predominantly activated by exosomes
      and cytokines, whereas myeloid cells were activated by bacterial OMVs.

PMID- 28740180
TI  - Aspergillus labruscus sp. nov., a new species of Aspergillus section Nigri
      discovered in Brazil.
AB  - A novel fungal species, Aspergillus labruscus sp. nov., has been found in Brazil
      during an investigation of the fungal species present on the surface of grape
      berries (Vitis labrusca L.) for use in the production of concentrated grape
      juice. It seems to be associated to V. labrusca, and has never been recovered
      from Vitis vinifera. This new species belonging to Aspergillus subgenus
      Circumdati section Nigri is described here using morphological characters,
      extrolite profiling, partial sequence data from the BenA and CaM genes, and
      internal transcribed spacer sequences of ribosomal DNA. Phenotypic and molecular
      data enabled this novel species to be clearly distinguished from other black
      aspergilli. A. labruscus sp. nov. is uniseriate, has yellow mycelium, poor
      sporulation on CYA at 25  degrees C, abundant salmon to pink sclerotia and rough
      conidia. Neoxaline and secalonic acid D were consistently produced by isolates in
      this taxon. The type strain of A. labruscus sp. nov. is CCT 7800 (T) = ITAL
      22.223 (T) = IBT 33586 (T).

PMID- 28740181
TI  - Stage 1 development of a patient-reported experience measure (PREM) for chronic
      obstructive pulmonary disease (COPD).
AB  - : The study aimed to explore patients' experience of living with chronic
      obstructive pulmonary disease and their perspective of their community healthcare
      for chronic obstructive pulmonary disease to extract affective responses in order
      to develop potential items for a patient-reported experience measure for chronic
      obstructive pulmonary disease. Qualitative face-face interviews were conducted,
      in the community, with 64 patients with chronic obstructive pulmonary disease
      recruited from General Practices and Breathe-Easy community groups in the Outer
      North East, East and City areas of London and Essex, UK. A two phase analysis of
      the qualitative data was conducted to identify themes arising from patients'
      description of living with chronic obstructive pulmonary disease and their
      perceptions of their community healthcare and subsequently the affective
      responses underlying the themes raised by patients, which gave emotional colour
      to the themes, bringing the thematic analysis closer to the subjective patient
      experience. Five themes were identified from the interview data: 'Journey to
      diagnosis'; 'Smoking'; 'Usual care'; 'My everyday life'; and 'Exacerbations'.
      Twenty-one affective responses were identified and categorised as either
      'negative', 'positive' or 'bivalent'. 'Frustration', a negative affective
      response was prevalent in four themes. 'Gratitude', 'hope' and
      'happiness/enjoyment' were among the more positive responses more prevalent
      across several themes. By conducting a novel two-way analysis (thematic and
      affective) it was possible to identify themes and affective responses that were
      aligned to those themes. This enabled the development of 38 chronic obstructive
      pulmonary disease-specific experience items to take forward for further testing
      including item reduction and validity and reliability in the next stage of the
      patient-reported experience measure development. CHRONIC LUNG DISEASE: GIVING
      IMPORTANCE TO PATIENTS' EMOTIONS: An exploration of patient perceptions of living
      with chronic lung disease will help develop a new patient reported experience
      scale. Healthcare services are aiming to provide effective patient-centered care
      for those with chronic obstructive pulmonary disease (COPD). Such care strategies
      require structured, validated patient feedback scales to facilitate accurate
      communication between patients, carers and healthcare professionals. Susan Walker
      at Anglia Ruskin University in Chelmsford, UK, and co-workers analyzed
      qualitative data from interviews with 64 COPD patients in London and Essex
      regarding their emotions and perceptions of living with COPD, with the aim of
      creating a patient reported experience measure, or PREM. Initial results
      identified five themes-including 'journey to diagnosis' and 'everyday life'-and
      twenty-one affective responses, ranging from negative to positive. The team will
      take these results forward for further validation.

PMID- 28740182
TI  - Ultrahigh adsorption and singlet-oxygen mediated degradation for efficient
      synergetic removal of bisphenol A by a stable zirconium-porphyrin metal-organic
      framework.
AB  - Bisphenol A (BPA), one of 23 most important endocrine disrupting chemicals, was
      efficiently removed and sequentially photodegraded by a zirconium-porphyrin metal
      organic framework (MOF) catalyst under visible light for water treatment. Well
      control of photodegradation allows the kinetic separation of adsorption step and
      photodegradation step. Ultrahigh adsorption uptake of 487.69 +/- 8.37 mg g-1 is
      observed, while efficient photodegradation could be observed within 20 min at the
      rate of 0.004 mg min-1. The synergetic effect boosts the photocatalytic
      efficiency and confirms that the catalysis happens inside the MOF pores other
      than in the solution phase. Furthermore, the mechanism was elucidated by diverse
      control experiments, such as in the conditions of 1O2 scavenger, in darkness and
      with the changes of light sensitizing ligands. It confirmed that BPA was oxidized
      by the 1O2 which was generated from porphyrin ligand within MOFs under visible
      light. The excellent reusability and wide range of suitable pH range make the Zr
      porphyrin MOFs practical for the photocatalytic water treatment processes.

PMID- 28740183
TI  - Design and validation of a DNA-microarray for phylogenetic analysis of bacterial
      communities in different oral samples and dental implants.
AB  - The quali-quantitative characterization of the oral microbiota is crucial for an
      exhaustive knowledge of the oral ecology and the modifications of the microbial
      composition that occur during periodontal pathologies. In this study, we designed
      and validated a new phylogenetic DNA-microarray (OralArray) to quickly and
      reliably characterize the most representative bacterial groups that colonize the
      oral cavity. The OralArray is based on the Ligation Detection Reaction technology
      associated to Universal Arrays (LDR-UA), and includes 22 probe sets targeted to
      bacteria belonging to the phyla Firmicutes, Proteobacteria, Actinobacteria,
      Bacteroidetes, Fusobacteria, and Spirochaete. The tool is characterized by high
      specificity, sensitivity and reproducibility. The OralArray was successfully
      tested and validated on different oral samples (saliva, lingual plaque,
      supragingival plaque, and healing cap) collected from 10 healthy subjects. For
      each specimen, a microbial signature was obtained, and our results established
      the presence of an oral microbial profile specific for each subject. Moreover,
      the tool was applied to evaluate the efficacy of a disinfectant treatment on the
      healing caps before their usage. The OralArray is, thus, suitable to study the
      microbiota associated with various oral sites and to monitor changes arising from
      therapeutic treatments.

PMID- 28740184
TI  - Bridging the gap between measurements and modelling: a cardiovascular functional
      avatar.
AB  - Lumped parameter models of the cardiovascular system have the potential to assist
      researchers and clinicians to better understand cardiovascular function. The
      value of such models increases when they are subject specific. However, most
      approaches to personalize lumped parameter models have thus far required invasive
      measurements or fall short of being subject specific due to a lack of the
      necessary clinical data. Here, we propose an approach to personalize parameters
      in a model of the heart and the systemic circulation using exclusively non
      invasive measurements. The personalized model is created using flow data from
      four-dimensional magnetic resonance imaging and cuff pressure measurements in the
      brachial artery. We term this personalized model the cardiovascular avatar. In
      our proof-of-concept study, we evaluated the capability of the avatar to
      reproduce pressures and flows in a group of eight healthy subjects. Both
      quantitatively and qualitatively, the model-based results agreed well with the
      pressure and flow measurements obtained in vivo for each subject. This non
      invasive and personalized approach can synthesize medical data into clinically
      relevant indicators of cardiovascular function, and estimate hemodynamic
      variables that cannot be assessed directly from clinical measurements.

PMID- 28740185
TI  - An optical and electrical study of full thermally activated delayed fluorescent
      white organic light-emitting diodes.
AB  - We report on the engineering of full thermally activated delayed fluorescence -
      based white organic light emitting diodes (W-OLEDs) composed of three emitters
      (2,7-bis(9,9-dimethyl-acridin-10-yl)-9,9-dimethylthioxanthene-S,S-dioxide (DDMA
      TXO2), 2,7-bis(phenoxazin-10-yl)-9,9-dimethylthioxanthene-S,S-dioxide (DPO-TXO2)
      and 3,11-di(10H-phenoxazin-10-yl)dibenzo[a,j]phenazine (POZ-DBPHZ) in two
      different hosts. By controlling the device design through the study of the
      emission of DDMA-TXO2 and DPO-TXO2, the behaviour of POZ-DBPHZ in a device with
      more than one emitter, and the combination of the three materials, respectively,
      we show that external quantum efficiencies as high as 16% can be obtained for a
      structure with a correlated colour temperature close to warm white, together with
      colour rendering index close to 80. However it is in their performance stability
      that provides the true breakthrough: at 1000 cd/m2 the efficiencies were still
      above 10%, which is one of the best for this type of devices.

PMID- 28740187
TI  - Dark state with counter-rotating dissipative channels.
AB  - Dark state as a consequence of interference between different quantum states has
      great importance in the fields of chip-scale atomic clock and quantum
      information. For the Lambda-type three-level system, this dark state is generally
      regarded as being dissipation-free because it is a superposition of two lowest
      states without dipole transition between them. However, previous studies are
      based on the rotating-wave approximation (RWA) by neglecting the counter-rotating
      terms in the system-environment interaction. In this work, we study non-Markovian
      quantum dynamics of the dark state in a Lambda-type three-level system coupled to
      two bosonic baths and reveal the effect of counter-rotating terms on the dark
      state. In contrast to the dark state within the RWA, leakage of the dark state
      occurs even at zero temperature, as a result of these counter-rotating terms.
      Also, we present a method to restore the quantum coherence of the dark state by
      applying a leakage elimination operator to the system.

PMID- 28740186
TI  - Carotid sinus nerve electrical stimulation in conscious rats attenuates systemic
      inflammation via chemoreceptor activation.
AB  - Recent studies demonstrated a critical functional connection between the
      autonomic (sympathetic and parasympathetic) nervous and the immune systems. The
      carotid sinus nerve (CSN) conveys electrical signals from the chemoreceptors of
      the carotid bifurcation to the central nervous system where the stimuli are
      processed to activate sympathetic and parasympathetic efferent signals. Here, we
      reported that chemoreflex activation via electrical CSN stimulation, in conscious
      rats, controls the innate immune response to lipopolysaccharide attenuating the
      plasma levels of inflammatory cytokines such as tumor necrosis factor (TNF),
      interleukin 1beta (IL-1beta) and interleukin 6 (IL-6). By contrast, the
      chemoreflex stimulation increases the plasma levels of anti-inflammatory cytokine
      interleukin 10 (IL-10). This chemoreflex anti-inflammatory network was abrogated
      by carotid chemoreceptor denervation and by pharmacological blockade of either
      sympathetic - propranolol - or parasympathetic - methylatropine - signals. The
      chemoreflex stimulation as well as the surgical and pharmacological procedures
      were confirmed by real-time recording of hemodynamic parameters [pulsatile
      arterial pressure (PAP) and heart rate (HR)]. These results reveal, in conscious
      animals, a novel mechanism of neuromodulation mediated by the carotid
      chemoreceptors and involving both the sympathetic and parasympathetic systems.

PMID- 28740188
TI  - In situ stable crack growth at the micron scale.
AB  - Grain boundaries typically dominate fracture toughness, strength and slow crack
      growth in ceramics. To improve these properties through mechanistically informed
      grain boundary engineering, precise measurement of the mechanical properties of
      individual boundaries is essential, although it is rarely achieved due to the
      complexity of the task. Here we present an approach to characterize fracture
      energy at the lengthscale of individual grain boundaries and demonstrate this
      capability with measurement of the surface energy of silicon carbide single
      crystals. We perform experiments using an in situ scanning electron microscopy
      based double cantilever beam test, thus enabling viewing and measurement of
      stable crack growth directly. These experiments correlate well with our density
      functional theory calculations of the surface energy of the same silicon carbide
      plane. Subsequently, we measure the fracture energy for a bi-crystal of silicon
      carbide, diffusion bonded with a thin glassy layer.To improve mechanical
      properties in ceramics through grain boundary engineering, precise mechanical
      characterization of individual boundaries is vital yet difficult to achieve. Here
      authors perform experiments using an in situ scanning electron microscopy based
      double cantilever beam test, allowing to directly view and measure stable crack
      growth in silicon carbide.

PMID- 28740189
TI  - Aberrant Methylation of MEG3 Functions as a Potential Plasma-Based Biomarker for
      Cervical Cancer.
AB  - Methylation alterations of specific genes have recently been identified as
      diagnostic biomarkers for human cancers. Although MEG3 has been proved to be a
      tumor suppressor in cervical cancer according to our previous study, the
      diagnostic value of MEG3 methylation in plasma is still unknown. Therefore, the
      aim of this study is to identify a novel epigenetic biomarker for cervical
      cancer. In the current study, the level of MEG3 methylation was evaluated using
      methylation-specific polymerase chain reaction. The results showed that the level
      of MEG3 methylation was significantly higher in cervical cancer tissues and
      patients' plasmas than those in adjacent normal tissues and plasmas of healthy
      participants respectively. Moreover, the accuracy was good enough for MEG3
      methylation in plasma to discriminate CIN III patients from healthy participants.
      In addition, MEG3 methylation in plasma also has high discriminating power to
      predict HR-HPV infection and lymph node metastasis. Furthermore, hypermethylation
      of MEG3 in plasma was associated with worse recurrence-free and overall survival
      in cervical cancer patients. In conclusions, MEG3 methylation in plasma can serve
      as a diagnostic and prognostic biomarker for cervical cancer, providing useful
      information for clinical management.

PMID- 28740190
TI  - A magnetic topological semimetal Sr1-yMn1-zSb2 (y, z < 0.1).
AB  - Weyl (WSMs) evolve from Dirac semimetals in the presence of broken time-reversal
      symmetry (TRS) or space-inversion symmetry. The WSM phases in TaAs-class
      materials and photonic crystals are due to the loss of space-inversion symmetry.
      For TRS-breaking WSMs, despite numerous theoretical and experimental efforts, few
      examples have been reported. In this Article, we report a new type of magnetic
      semimetal Sr1-yMn1-zSb2 (y, z < 0.1) with nearly massless relativistic fermion
      behaviour (m* =  0.04 - 0.05m0, where m0 is the free-electron mass). This
      material exhibits a ferromagnetic order for 304 K  <  T  <  565 K, but a canted
      antiferromagnetic order with a ferromagnetic component for T  <  304 K. The
      combination of relativistic fermion behaviour and ferromagnetism in Sr1-yMn1-zSb2
      offers a rare opportunity to investigate the interplay between relativistic
      fermions and spontaneous TRS breaking.

PMID- 28740191
TI  - An in-silico glimpse into the pH dependent structural changes of T7 RNA
      polymerase: a protein with simplicity.
AB  - The capability of performing an array of functions with its single subunit
      structure makes T7 RNA polymerase (T7RNAP) as one of the simplest yet attractive
      target for various investigations ranging from structure determinations to
      several biological tests. In this study, with the help of molecular dynamics (MD)
      calculations and molecular docking, we investigated the effect of varying pH
      conditions on conformational flexibility of T7RNAP. We also studied its effect on
      the interactions with a well established inhibitor (heparin), substrate GTP and
      T7 promoter of T7RNAP. The simulation studies were validated with the help of
      three dimensional reconstructions of the polymerase at different pH environments
      using transmission electron microscopy and single particle analysis. On comparing
      the simulated structures, it was observed that the structure of T7RNAP changes
      considerably and interactions with its binding partners also changes as the pH
      shifts from basic to acidic. Further, it was observed that the C-terminal end
      plays a vital role in the inefficiency of the polymerase at low pH. Thus, this in
      silico study may provide a significant insight into the structural investigations
      on T7RNAP as well as in designing potent inhibitors against it in varying pH
      environments.

PMID- 28740194
TI  - THE "METHOD OF GAME": SANDOR FERENCZI AND HIS PATIENT DM./CLARA THOMPSON.
AB  - The aim of this paper is to study the Thompson-Ferenczi therapeutic relationship.
      Ferenczi paid increasing attention to the way in which patient's early life
      experiences were reenacted in the transference countertransference matrix.
      Ferenczi's (1931) description of how he "entered into a game" with a patient, has
      come to be known as enactment. Ferenczi exchanged the word "game" with "play"
      when patients enacted their past traumatic experiences in analysis. These
      enactments uncovered the unconscious "dialogue of the game" (Ferenczi, 1932, p.
      130), and Ferenczi described them in his Clinical Diary (1932) in his work with
      Thompson. Using the language of her analyst in describing enactment, Thompson
      referred to Ferenczi's Relaxation Method as his "play technique". During these
      moments of "play" Thompson argues that the analyst cooperates with the patient in
      allowing him to relive "childish attachments" in the context of the treatment.

PMID- 28740192
TI  - Preventive effect of celecoxib use against cancer progression and occurrence of
      oral squamous cell carcinoma.
AB  - Overexpression of cyclooxygenase-2 in oral cancer increases lymph node metastasis
      and is associated with a poor prognosis. The potential of celecoxib (CXB) use is
      reported in cancer treatment by inhibiting proliferation through apoptosis, but
      the effects on the epithelial-mesenchymal transition (EMT) and cancer cell
      mobility remain unclear. We performed a preclinical study and population-based
      study to evaluate CXB use in the prevention of oral cancer progression and
      occurrence. The in-vitro findings showed that CXB is involved in the inhibition
      of EMT and cell mobility through blocking transcription factors (Slug, Snail and
      ZEB1), cytoplasmic mediators (focal adhesion kinase (FAK), vimentin and beta
      catenin), cell adhesion molecules (cadherins and integrins), and surface
      receptors (AMFR and EGFR). The murine xenograft model showed a 65% inhibition in
      tumour growth after a 5-week treatment of CXB compared to placebo. Xenograft
      tumours in placebo-treated mice displayed a well-to-moderate/moderate
      differentiated SCC grade, while those from CXB-treated mice were well
      differentiated. The expression levels of membrane EGFR, and nuclear FAK, Slug and
      ZEB1 were decreased in the xenograft tumours of CXB-treated mice. A retrospective
      cohort study showed that increasing the daily dose and medication time of CXB was
      associated with oral cancer prevention. The findings provide an alternative
      prevention strategy for oral cancer development with CXB use.

PMID- 28740195
TI  - Searching for a Sensitive Way of Working Through.
AB  - This work intends to present aspects of clinical work in which the Ferenczian
      proposition of neo-catharsis, as re-emergence of repressed affective experience
      in the transference and countertransference presents itself as a challenge to the
      analyst, since a standard, classical technical approach results in repetition of
      past trauma with the analyst as perpetrator. A deviation from standard technique
      free association, the principle of abstinence in transference, and interpretation
      involving empathic listening, and affective sharing contains the patient's
      suffering. The re-emergence of suffering and terror, which represents the
      repressed affect associated with the traumatic past, but with a sympathetic and
      sensitive analyst, sharing their experience, is crucial in working through and
      healing.

PMID- 28740197
TI  - UNTOLD STORIES AND THE POWER OF SILENCE IN THE INTERGENERATIONAL TRANSMISSION OF
      SOCIAL TRAUMA.
AB  - There are intergenerational secrets and unprocessed experiences that very often
      don't have a voice or an image associated with them but loom in our minds
      nonetheless. What haunts are not the dead, but the gaps left within us by the
      secrets of others. This paper will look at the conflict that occurs when unspoken
      events and memories of one generation haunt the next one. It is my contention
      that the second-generation survivors of trauma can be deeply affected by
      something that did not directly happen to them. Utilizing my own personal
      narrative I will examine how being the daughter of a woman who escaped the
      Holocaust, and her silence about those events affected my personal development
      and later my work with patients. I will also explore the unspoken secret that a
      patient's mother kept from her, paralleling the writer's mother's secret.

PMID- 28740198
TI  - The Drive For Self-Assertion And The Reality Principle In A Patient With
      Malignant Pleural Mesothelioma: The History of Giulia.
AB  - Life in a contaminated environment is often marked by a cumulative psychological
      trauma that exhibits a variety of social-environmental aspects. This is why I
      suggested a psychotherapeutic group intervention for the population of Casale
      Monferrato, a municipality in Northern Italy that is sadly renowned for asbestos
      related events and the high mortality rate of its inhabitants. Groupality appears
      to show the point of contact between psyche and soma, while also promoting the
      birth of a more realistic approach to the various levels of suffering and their
      configuration. The multifamily approach seemed to be the most adequate to
      elaborate the feelings of rage and fear that are concurrent with the aerial
      contagion. In the "long wave" of group work we have learned to work with
      participants as well as with empty chairs, the ghosts of the dead: live traces in
      the mind. Whereas the mind recovers the possibility of entering into a dialogue
      with the feelings connected to the trauma, without bypassing them towards actions
      that are apparently more assertive of one's sense of Ego, the will of
      conciliation can reactivate a thought that is oriented towards the plane of
      reality.

PMID- 28740199
TI  - Fermi surface topology and signature of surface Dirac nodes in LaBi.
AB  - Novel topological state of matter is one of the rapidly growing fields in
      condensed matter physics research in recent times. While these materials are
      fascinating from the aspect of fundamental physics of relativistic particles,
      their exotic transport properties are equally compelling due to the potential
      technological applications. Extreme magnetoresistance and ultrahigh carrier
      mobility are two such major hallmarks of topological materials and often used as
      primary criteria for identifying new compounds belonging to this class. Recently,
      LaBi has emerged as a new system, which exhibits the above mentioned properties.
      However, the topological nature of its band structure remains unresolved. Here,
      using the magnetotransport and magnetization measurements, we have probed the
      bulk and surface states of LaBi. Similar to earlier reports, extremely large
      magnetoresistance and high carrier mobility have been observed with compensated
      electron and hole density. The Fermi surface properties have been analyzed from
      both Shubnikov-de Haas and de Haas-van Alphen oscillation techniques. In the
      magnetization measurement, a prominent paramagnetic singularity has been
      observed, which demonstrates the non-trivial nature of the surface states in
      LaBi. Our study unambiguously confirms that LaBi is a three-dimensional
      topological insulator with possible linear dispersion in the gapped bulk band
      structure.

PMID- 28740200
TI  - Physiologically-based modelling in mice suggests an aggravated loss of clearance
      capacity after toxic liver damage.
AB  - Diseases and toxins may lead to death of active liver tissue, resulting in a loss
      of total clearance capacity at the whole-body level. However, it remains
      difficult to study, whether the loss of metabolizing tissue is sufficient to
      explain loss of metabolic capacity of the liver or whether the surviving tissue
      undergoes an adaptive response to compensate the loss. To understand the cellular
      impact of toxic liver damage in an in vivo situation, we here used
      physiologically-based pharmacokinetic modelling to investigate pharmacokinetics
      of a specifically designed drug cocktail at three different sampling sites of the
      body in healthy mice and mice treated with carbon tetrachloride (CCl4). Liver
      zonation was explicitly quantified in the models through immunostaining of
      cytochrome P450s enzymes. Comparative analyses between the simulated decrease in
      clearance capacity and the experimentally measured loss in tissue volume
      indicated that CCl4-induced impairment of metabolic functions goes beyond the
      mere loss of metabolically active tissue. The here established integrative
      modelling strategy hence provides mechanistic insights into functional
      consequences of toxic liver damage in an in vivo situation, which would not have
      been accessible by conventional methods.

PMID- 28740201
TI  - Promoting Singlet/triplet Exciton Transformation in Organic Optoelectronic
      Molecules: Role of Excited State Transition Configuration.
AB  - Exciton transformation, a non-radiative process in changing the spin multiplicity
      of an exciton usually between singlet and triplet forms, has received much
      attention recently due to its crucial effects in manipulating optoelectronic
      properties for various applications. However, current understanding of exciton
      transformation mechanism does not extend far beyond a thermal equilibrium of two
      states with different multiplicity and it is a significant challenge to probe
      what exactly control the transformation between the highly active excited states.
      Here, based on the recent developments of three types of purely organic molecules
      capable of efficient spin-flipping, we perform ab initio structure/energy
      optimization and similarity/overlap extent analysis to theoretically explore the
      critical factors in controlling the transformation process of the excited states.
      The results suggest that the states having close energy levels and similar
      exciton characteristics with same transition configurations and high heteroatom
      participation are prone to facilitating exciton transformation. A basic guideline
      towards the molecular design of purely organic materials with facile exciton
      transformation ability is also proposed. Our discovery highlights systematically
      the critical importance of vertical transition configuration of excited states in
      promoting the singlet/triplet exciton transformation, making a key step forward
      in excited state tuning of purely organic optoelectronic materials.

PMID- 28740202
TI  - Prior-knowledge Fitting of Accelerated Five-dimensional Echo Planar J-resolved
      Spectroscopic Imaging: Effect of Nonlinear Reconstruction on Quantitation.
AB  - 1H Magnetic Resonance Spectroscopic imaging (SI) is a powerful tool capable of
      investigating metabolism in vivo from mul- tiple regions. However, SI techniques
      are time consuming, and are therefore difficult to implement clinically. By
      applying non-uniform sampling (NUS) and compressed sensing (CS) reconstruction,
      it is possible to accelerate these scans while re- taining key spectral
      information. One recently developed method that utilizes this type of
      acceleration is the five-dimensional echo planar J-resolved spectroscopic imaging
      (5D EP-JRESI) sequence, which is capable of obtaining two-dimensional (2D)
      spectra from three spatial dimensions. The prior-knowledge fitting (ProFit)
      algorithm is typically used to quantify 2D spectra in vivo, however the effects
      of NUS and CS reconstruction on the quantitation results are unknown. This study
      utilized a simulated brain phantom to investigate the errors introduced through
      the acceleration methods. Errors (normalized root mean square error >15%) were
      found between metabolite concentrations after twelve-fold acceleration for
      several low concentra- tion (<2 mM) metabolites. The Cramer Rao lower bound%
      (CRLB%) values, which are typically used for quality control, were not reflective
      of the increased quantitation error arising from acceleration. Finally, occipital
      white (OWM) and gray (OGM) human brain matter were quantified in vivo using the
      5D EP-JRESI sequence with eight-fold acceleration.

PMID- 28740203
TI  - Homeostatic Left Heart integration and disintegration links atrio-ventricular
      covariation's dyshomeostasis in Hypertrophic Cardiomyopathy.
AB  - Left ventricle and left atrium are and have been practically always analyzed
      separately in common clinically and non-clinically oriented cardiovascular
      investigations. Both classic and speckle tracking echocardiographic data
      contributed to the knowledge about deformational impairments occurring in systo
      diastolic differences. Recently new trajectory based approaches allowed a greater
      awareness about the entire left ventricle or left atrium revolution and on their
      deficiencies that take place in presence of hypertrophic cardiomyopathy. However,
      surprisingly, the concomitant function of the two left heart chambers has not
      been analyzed for their geometrical/mechanical relationship. For the first time
      we study here, by acquiring left ventricle and left atrial geometries on the same
      heartbeat, the trajectory attributes of the entire left heart treated as a whole
      shape and the shape covariation of its two subunits. We contrasted healthy
      subjects with patients affected by hypertrophic cardiomyopathy. We found impaired
      left heart trajectory mainly in terms of orientation and size. More importantly,
      we found profound differences in the direction of morphological covariation of
      left ventricle and left atrium. These findings open to new perspectives in
      pathophysiological evaluation of different diseases by allowing the appreciation
      of concomitant functioning of both left heart whole geometry and of its two
      chambers.

PMID- 28740205
TI  - A diatomic elastic metamaterial for tunable asymmetric wave transmission in
      multiple frequency bands.
AB  - Unidirectional/asymmetric transmission of acoustic/elastic waves has recently
      been realized by linear structures. Research related to unidirectionality of wave
      propagation has received intense attention due to potentially transformative and
      unique wave control applications. However, asymmetric transmission performance in
      existing devices usually occurs only in a narrow frequency band, and the
      asymmetric frequencies are always within ultrasound range (above 20 kHz). In this
      work, we design and propose a linear diatomic elastic metamaterial using dual
      resonator concept to obtain large asymmetric elastic wave transmission in
      multiple low frequency bands. All of these frequency bands can be theoretically
      predicted to realize one-way wave propagation along different directions of
      transmission. The mechanisms of multiple asymmetric transmission bands are
      theoretically investigated and numerically verified by both analytical lattice
      and continuum models. Dynamic responses of the proposed system in the broadband
      asymmetric transmission bands are explored and analyzed in time and frequency
      domains. The effect of damping on the asymmetric wave transmission is further
      discussed. Excellent agreements between theoretical results and numerical
      verification are obtained.

PMID- 28740204
TI  - Safety and tolerability of topically administered autologous, apoptotic PBMC
      secretome (APOSEC) in dermal wounds: a randomized Phase 1 trial (MARSYAS I ).
AB  - Developing effective therapies against chronic wound healing deficiencies is a
      global priority. Thus we evaluated the safety of two different doses of topically
      administered autologous APOSEC, the secretome of apoptotic peripheral blood
      mononuclear cells (PBMCs), in healthy male volunteers with artificial dermal
      wounds. Ten healthy men were enrolled in a single-center, randomized, double
      blinded, placebo-controlled phase 1 trial. Two artificial wounds at the upper arm
      were generated using a 4-mm punch biopsy. Each participant was treated with both
      topically applied APOSEC and placebo in NuGel for 7 consecutive days. The
      volunteers were randomized into two groups: a low-dose group (A) receiving the
      supernatant of 12.5 * 106 PBMCs and a high-dose group (B) receiving an equivalent
      of 25 * 106 PBMCs resuspended in NuGel Hydrogel. Irradiated medium served as
      placebo. The primary outcome was the tolerability of the topical application of
      APOSEC. All adverse events were recorded until 17 days after the biopsy. Local
      tolerability assessment was measured on a 4-point scale. Secondary outcomes were
      wound closure and epithelization at day 7. No therapy-related serious adverse
      events occurred in any of the participants, and both low- and high-dose
      treatments were well tolerated. Wound closure was not affected by APOSEC therapy.

PMID- 28740206
TI  - Relation between Arterial Stiffness and Markers of Inflammation and Hemostasis -
      Data from the Population-based Gutenberg Health Study.
AB  - The relation between inflammation, hemostasis and arterial stiffness is of
      pathophysiological relevance for the development of cardiovascular disease (CVD).
      Data investigating this interplay using stiffness index (SI) by digital
      photoplethysmography are not available yet. Therefore, sex-specific relation
      between SI and inflammatory and hemostatic biomarkers was investigated within
      13,724 subjects from the population-based Gutenberg Health Study. C-reactive
      protein (CRP), white blood cell count (WBCC), neopterin, interleukin-18,
      interleukin-1 receptor antagonist (IL-1RA), fibrinogen and hematocrit were
      measured. Multivariable linear regression analysis with adjustment for
      cardiovascular risk factors, medication, and hormonal status (in females)
      revealed an independent association between SI and WBCC, IL-1RA and hematocrit in
      both sexes, and with fibrinogen in women. There was a joint effect of increasing
      tertiles of SI and biomarker concentrations for future CVD risk prediction.
      Subjects with both SI and biomarker concentration above the median had the worst
      overall survival and with both below the median the best survival during a follow
      up period of 6.2 +/- 1.7 years, except for hematocrit. The results support the
      relation between inflammation, hemostasis and arterial stiffness measured by
      digital photoplethysmography. Markers of inflammation and hemostasis modulate the
      ability of SI to identify subjects at risk for future CVD or higher mortality.

PMID- 28740207
TI  - High Energy Radical Chemistry Formation of HCN-rich Atmospheres on early Earth.
AB  - Recent results in prebiotic chemistry implicate hydrogen cyanide (HCN) as the
      source of carbon and nitrogen for the synthesis of nucleotide, amino acid and
      lipid building blocks. HCN can be produced during impact events by reprocessing
      of carbonaceous and nitrogenous materials from both the impactor and the
      atmosphere; it can also be produced from these materials by electrical discharge.
      Here we investigate the effect of high energy events on a range of starting
      mixtures representative of various atmosphere-impactor volatile combinations.
      Using continuously scanning time-resolved spectrometry, we have detected .CN
      radical and excited CO as the initially most abundant products. Cyano radicals
      and excited carbon monoxide molecules in particular are reactive, energy-rich
      species, but are resilient owing to favourable Franck-Condon factors. The
      subsequent reactions of these first formed excited species lead to the production
      of ground-state prebiotic building blocks, principally HCN.

PMID- 28740208
TI  - Temporal dynamics of whole body residues of the neonicotinoid insecticide
      imidacloprid in live or dead honeybees.
AB  - In cases of acute intoxication, honeybees often lay in front of their hives for
      several days, exposed to sunlight and weather, before a beekeeper can take a
      sample. Beekeepers send samples to analytical laboratories, but sometimes no
      residues can be detected. Temperature and sun light could influence the decrease
      of pesticides in bee samples and thereby residues left for analysis. Moreover,
      samples are usually sent via normal postal services without cooling. We
      investigated the temporal dynamics of whole-body residues of imidacloprid in live
      or dead honeybees following a single-meal dietary exposure of 41 ng/bee under
      various environmental conditions, such as freezing, exposure to UV light or
      transfer of individuals through the mail system. Immobile, "dead" looking
      honeybees recovered from paralysis after 48 hours. The decrease of residues in
      living but paralysed bees was stopped by freezing (= killing). UV light
      significantly reduced residues, but the mode of transport did not affect residue
      levels. Group feeding increased the variance of residues, which is relevant for
      acute oral toxicity tests. In conclusion, elapsed time after poisoning is key for
      detection of neonicotinoids. Freezing before mailing significantly reduced the
      decrease of imidacloprid residues and may increase the accuracy of laboratory
      analysis for pesticides.

PMID- 28740209
TI  - Novel risk genes for systemic lupus erythematosus predicted by random forest
      classification.
AB  - Genome-wide association studies have identified risk loci for SLE, but a large
      proportion of the genetic contribution to SLE still remains unexplained. To
      detect novel risk genes, and to predict an individual's SLE risk we designed a
      random forest classifier using SNP genotype data generated on the "Immunochip"
      from 1,160 patients with SLE and 2,711 controls. Using gene importance scores
      defined by the random forest classifier, we identified 15 potential novel risk
      genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE,
      whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated
      with autoimmunity. Random forest classification also allowed prediction of
      patients at risk for lupus nephritis with an area under the curve of 0.94. By
      allele-specific gene expression analysis we detected cis-regulatory SNPs that
      affect the expression levels of six of the top 40 genes designed by the random
      forest analysis, indicating a regulatory role for the identified risk variants.
      The 40 top genes from the prediction were overrepresented for differential
      expression in B and T cells according to RNA-sequencing of samples from five
      healthy donors, with more frequent over-expression in B cells compared to T
      cells.

PMID- 28740210
TI  - Elucidating the mechanisms underlying the beneficial health effects of dietary
      pollen on honey bees (Apis mellifera) infested by Varroa mite ectoparasites.
AB  - Parasites and pathogens of the honey bee (Apis mellifera) are key factors
      underlying colony losses, which are threatening the beekeeping industry and
      agriculture as a whole. To control the spread and development of pathogen
      infections within the colony, honey bees use plant resins with antibiotic
      activity, but little is known about the properties of other substances, that are
      mainly used as a foodstuff, for controlling possible diseases both at the
      individual and colony level. In this study, we tested the hypothesis that pollen
      is beneficial for honey bees challenged with the parasitic mite Varroa destructor
      associated to the Deformed Wing Virus. First, we studied the effects of pollen on
      the survival of infested bees, under laboratory and field conditions, and
      observed that a pollen rich diet can compensate the deleterious effects of mite
      parasitization. Subsequently, we characterized the pollen compounds responsible
      for the observed positive effects. Finally, based on the results of a
      transcriptomic analysis of parasitized bees fed with pollen or not, we developed
      a comprehensive framework for interpreting the observed effects of pollen on
      honey bee health, which incorporates the possible effects on cuticle integrity,
      energetic metabolism and immune response.

PMID- 28740211
TI  - Digging up food: excavation stone tool use by wild capuchin monkeys.
AB  - Capuchin monkeys at Serra da Capivara National Park (SCNP) usually forage on the
      ground for roots and fossorial arthropods, digging primarily with their hands but
      also using stone tools to loosen the soil and aid the digging process. Here we
      describe the stone tools used for digging by two groups of capuchins on SCNP.
      Both groups used tools while digging three main food resources: Thiloa
      glaucocarpa tubers, Ocotea sp roots, and trapdoor spiders. One explanation for
      the occurrence of tool use in primates is the "necessity hypothesis", which
      states that the main function of tool use is to obtain fallback food. We tested
      for this, but only found a positive correlation between plant food availability
      and the frequency of stone tools' use. Thus, our data do not support the fallback
      food hypothesis for the use of tools to access burrowed resources.

PMID- 28740212
TI  - Phonon Conduction in Silicon Nanobeam Labyrinths.
AB  - Here we study single-crystalline silicon nanobeams having 470 nm width and 80 nm
      thickness cross section, where we produce tortuous thermal paths (i.e.
      labyrinths) by introducing slits to control the impact of the unobstructed "line
      of-sight" (LOS) between the heat source and heat sink. The labyrinths range from
      straight nanobeams with a complete LOS along the entire length to nanobeams in
      which the LOS ranges from partially to entirely blocked by introducing slits, s =
      95, 195, 245, 295 and 395 nm. The measured thermal conductivity of the samples
      decreases monotonically from ~47 W m-1 K-1 for straight beam to ~31 W m-1 K-1 for
      slit width of 395 nm. A model prediction through a combination of the Boltzmann
      transport equation and ab initio calculations shows an excellent agreement with
      the experimental data to within ~8%. The model prediction for the most tortuous
      path (s = 395 nm) is reduced by ~14% compared to a straight beam of equivalent
      cross section. This study suggests that LOS is an important metric for
      characterizing and interpreting phonon propagation in nanostructures.

PMID- 28740213
TI  - Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by
      Addition of Alanyl-Glutamine to Dialysis Fluid.
AB  - Peritonitis remains a major cause of morbidity and mortality during chronic
      peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses
      in the peritoneal cavity. Low concentrations of peritoneal extracellular
      glutamine during PD may contribute to this immune deficit. For these reasons we
      have developed a clinical assay to measure the function of the immune-competent
      cells in PD effluent from PD patients. We then applied this assay to test the
      impact on peritoneal immune-competence of PD fluid supplementation with alanyl
      glutamine (AlaGln) in 6 patients in an open-label, randomized, crossover pilot
      trial (EudraCT 2012-004004-36), and related the functional results to
      transcriptome changes in PD effluent cells. Ex-vivo stimulation of PD effluent
      peritoneal cells increased release of interleukin (IL) 6 and tumor necrosis
      factor (TNF) alpha. Both IL-6 and TNF-alpha were lower at 1 h than at 4 h of the
      peritoneal equilibration test but the reductions in cytokine release were
      attenuated in AlaGln-supplemented samples. AlaGln-supplemented samples exhibited
      priming of IL-6-related pathways and downregulation of TNF-alpha upstream
      elements. Results from measurement of cytokine release and transcriptome analysis
      in this pilot clinical study support the conclusion that suppression of PD
      effluent cell immune function in human subjects by standard PD fluid is
      attenuated by AlaGln supplementation.

PMID- 28740214
TI  - Compensatory anabolic signaling in the sarcopenia of experimental chronic
      arthritis.
AB  - Inflammatory activity in rheumatoid arthritis may alter the regulation of muscle
      mass leading to a secondary sarcopenia, commonly termed rheumatoid cachexia (RC).
      We characterized alterations to muscle structure and various pro-inflammatory,
      catabolic and regenerative markers in an animal model of RC. Antigen induced
      arthritis (AiA) was performed in 20 male adult rabbits. AiA animals exhibited
      significantly less weight gain, a markedly elevated serum C-reactive protein
      (CRP), lighter muscles with shorter cross-sectional diameter and increased
      myonuclei when compared to controls. Atrogin-1 and MuRF-1 were up-regulated
      alongside an increase in IL-1beta, active NF-kappaB and a higher ratio of
      phosphorylated to inactive p38 MAPK. CCL-2 and TNF levels were reduced and IL-6
      was unchanged between groups. We observed decreased pSTAT3, unchanged pSTAT1 and
      Myf5, but increased Pax7, MyoD and myogenin. AiA rabbits had a reduction in
      myostatin from gastrocnemii and synovium with a congruent decrease in serum
      myostatin compared to controls. Chronic arthritis induced an RC-like secondary
      sarcopenia with increased muscle protein breakdown. Elevated IL-1beta may trigger
      proteolysis via elevated NF-kappaB and p38 MAPK signaling with a compensatory
      anabolic response suggested by myonuclear expansion, increased Pax7, MyoD and
      myogenin, reduced pSTAT3 as well as reduced serum, synovial and muscular
      myostatin.

PMID- 28740215
TI  - Quantitative analysis of 3D alignment quality: its impact on soft-validation,
      particle pruning and homogeneity analysis.
AB  - Single Particle Analysis using cryo-electron microscopy is a structural biology
      technique aimed at capturing the three-dimensional (3D) conformation of
      biological macromolecules. Projection images used to construct the 3D density map
      are characterized by a very low signal-to-noise ratio to minimize radiation
      damage in the samples. As a consequence, the 3D image alignment process is a
      challenging and error prone task which usually determines the success or failure
      of obtaining a high quality map. In this work, we present an approach able to
      quantify the alignment precision and accuracy of the 3D alignment process, which
      is then being used to help the reconstruction process in a number of ways, such
      as: (1) Providing quality indicators of the macromolecular map for soft
      validation, (2) Assessing the degree of homogeneity of the sample and, (3),
      Selecting subsets of representative images. We present experimental results in
      which the quality of the finally obtained 3D maps is clearly improved.

PMID- 28740216
TI  - Universality of maximum-work efficiency of a cyclic heat engine based on a finite
      system of ultracold atoms.
AB  - We study the performance of a cyclic heat engine which uses a small system with a
      finite number of ultracold atoms as its working substance and works between two
      heat reservoirs at constant temperatures T h and T c (<T h ). Starting from the
      expression of heat capacity which includes finite-size effects, the work output
      is optimized with respect to the temperature of the working substance at a
      special instant along the cycle. The maximum-work efficiency eta mw at small
      relative temperature difference can be expanded in terms of the Carnot value
      [Formula: see text], [Formula: see text], where a 0 is a function depending on
      the particle number N and becomes vanishing in the symmetric case. Moreover, we
      prove using the relationship between the temperatures of the working substance
      and heat reservoirs that the maximum-work efficiency, when accurate to the first
      order of eta C , reads [Formula: see text](DeltaT 2). Within the framework of
      linear irreversible thermodynamics, the maximum-power efficiency is obtained as
      [Formula: see text](DeltaT 2) through appropriate identification of thermodynamic
      fluxes and forces, thereby showing that this kind of cyclic heat engines satisfy
      the tight-coupling condition.

PMID- 28740217
TI  - Emergent electronic structure of CaFe2As2.
AB  - CaFe2As2 exhibits collapsed tetragonal (cT) structure and varied exotic behaviour
      under pressure at low temperatures that led to debate on linking the structural
      changes to its exceptional electronic properties like superconductivity,
      magnetism, etc. Here, we investigate the electronic structure of CaFe2As2 forming
      in different structures employing density functional theory. The results indicate
      that the stability of the cT phase under pressure arises from the enhancement in
      hybridization induced effects and shift of the energy bands towards lower
      energies. The Fermi surface centered around Gamma point gradually vanishes with
      the increase in pressure. Consequently, the nesting between the hole and electron
      Fermi surfaces associated to the spin density wave state disappears indicating a
      pathway to achieve the proximity to quantum fluctuations. The magnetic moment at
      the Fe sites diminishes in the cT phase consistent with the magnetic
      susceptibility results. Notably, the hybridization of Ca 4s states (Ca-layer may
      be treated as a charge reservoir layer akin to those in cuprate superconductors)
      is significantly enhanced in the cT phase revealing its relevance in its
      interesting electronic properties.

PMID- 28740218
TI  - A rare and extensive summer bloom enhanced by ocean eddies in the oligotrophic
      western North Pacific Subtropical Gyre.
AB  - The North Pacific Subtropical Gyre (NPSG) is the largest ecosystem on Earth, and
      it plays a critical role in global ocean productivity and carbon cycling. Here,
      we report a rare and striking ~2000-km-long phytoplankton bloom that lasted over
      one month in the western part of the NPSG in summer 2003. The bloom resulted from
      the co-occurrence of a northward-shifted North Equatorial Current (NEC) supplying
      additional phosphate, and strong eddy activity that fueled productivity and
      spread chlorophyll mainly through horizontal stirring. The extensive one-month
      bloom had a maximum Chl concentration of six times the summer mean value and
      collectively fixed an additional five teragrams (5 * 1012 g) of carbon above the
      summer average. An increase in the pCO2 during the bloom suggests that most of
      the additionally fixed carbon was rapidly consumed.

PMID- 28740219
TI  - Role of p66shc in skeletal muscle function.
AB  - p66shc is a growth factor adaptor protein that contributes to mitochondrial ROS
      production. p66shc is involved in insulin signaling and its deletion exerts a
      protective effect against diet-induced obesity. In light of the role of skeletal
      muscle activity in the control of systemic metabolism and obesity, we
      investigated which is the contribution of p66shc in regulating muscle structure
      and function. Here, we show that p66shc-/- muscles are undistinguishable from
      controls in terms of size, resistance to denervation-induced atrophy, and force.
      However, p66shc-/- mice perform slightly better than wild type animals during
      repetitive downhill running. Analysis of the effects after placing mice on a high
      fat diet (HFD) regimen demonstrated that running distance is greatly reduced in
      obese wild type animals, but not in overweight-resistant p66shc-/- mice. In
      addition, muscle force measured after exercise decreases upon HFD in wild type
      mice while p66shc-/- animals are protected. Our data indicate that p66shc affect
      the response to damage of adult muscle in chow diet, and it determines the
      maintenance of muscle force and exercise performance upon a HFD regimen.

PMID- 28740220
TI  - The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action
      of insulin.
AB  - Defective hepatic autophagy is observed in obesity and diabetes, whereas
      autophagy is inhibited by insulin in hepatocytes. Insulin-induced anti-autophagy
      is mediated by non-canonical Galphai3 signaling via an unknown mechanism.
      Previously, we identified the anti-autophagic activity of Tnfaip8 via activation
      of mammalian target of rapamycin (mTOR) in the nervous system. Here, we
      demonstrate that insulin temporally induces Tnfaip8, which mediates the anti
      autophagic action of insulin through formation of a novel ternary complex
      including Tnfaip8, phosphatidylethanolamine (PE) and Galphai3. Specifically, an X
      ray crystallographic study of Tnfaip8 from Mus musculus (mTnfaip8) at 2.03 A
      together with LC-MS analyses reveals PE in the hydrophobic cavity. However, an
      mTnfaip8 mutant lacking PE does not interact with Galphai3, indicating that the
      PE component is critical for the anti-autophagic action of mTnfaip8 via
      interaction with Galphai3. Therefore, the mTnfaip8-PE complex may act as an
      essential upstream effector via ternary complex formation most likely with active
      Galphai3 during insulin-induced anti-autophagy.

PMID- 28740221
TI  - Escape from humoral immunity is associated with treatment failure in HIV-1
      infected patients receiving long-term antiretroviral therapy.
AB  - Interindividual heterogeneity in the disease progression of HIV-1-infected
      patients receiving long-term antiretroviral therapy suggests that some host
      related factors may have limited treatment efficacy. To understand the nature of
      factors contributing to treatment failure, we performed a retrospective cohort
      study of 45 chronically HIV-1-infected individuals sharing a similar demographics
      and route of infection, compared the differences between virologically suppressed
      (VS) and treatment failure (TF) patients with respect to clinical, immunological
      and virological characteristics. We found that the baseline diversity of HIV-1
      env quasispecies was the major difference between VS and TF group, and higher
      baseline diversity in TF patients. We further predicted TF-related env mutations
      using a selection pressure-based approach, followed by an analysis of these
      mutations based on the available three-dimensional structures of gp120/gp41 or
      their complexes with neutralizing antibodies. Notably, almost all of the
      identified residues could be mapped to the epitopes of known HIV-1 neutralizing
      antibodies, especially the epitopes of broadly neutralizing antibodies, and these
      mutations tended to compromise antibody-antigen interactions. These results
      indicate that the escape of HIV-1 from host humoral immunity may play a direct
      role in TF in long-term antiretroviral-experienced patients and that based on env
      gene sequence of the viruses in the patients.

PMID- 28740222
TI  - Primary fibroblasts from CSPalpha mutation carriers recapitulate hallmarks of the
      adult onset neuronal ceroid lipofuscinosis.
AB  - Mutations in the co- chaperone protein, CSPalpha, cause an autosomal dominant,
      adult-neuronal ceroid lipofuscinosis (AD-ANCL). The current understanding of
      CSPalpha function exclusively at the synapse fails to explain the autophagy
      lysosome pathway (ALP) dysfunction in cells from AD-ANCL patients. Here, we
      demonstrate unexpectedly that primary dermal fibroblasts from pre-symptomatic
      mutation carriers recapitulate in vitro features found in the brains of AD-ANCL
      patients including auto-fluorescent storage material (AFSM) accumulation,
      CSPalpha aggregates, increased levels of lysosomal proteins and lysosome enzyme
      activities. AFSM accumulation correlates with CSPalpha aggregation and both are
      susceptible to pharmacological modulation of ALP function. In addition, we
      demonstrate that endogenous CSPalpha is present in the lysosome-enriched
      fractions and co-localizes with lysosome markers in soma, neurites and synaptic
      boutons. Overexpression of CSPalpha wild-type (WT) decreases lysotracker signal,
      secreted lysosomal enzymes and SNAP23-mediated lysosome exocytosis. CSPalpha WT,
      mutant and aggregated CSPalpha are degraded mainly by the ALP but this disease
      causing mutation exhibits a faster rate of degradation. Co-expression of both WT
      and mutant CSPalpha cause a block in the fusion of autophagosomes/lysosomes. Our
      data suggest that aggregation-dependent perturbation of ALP function is a
      relevant pathogenic mechanism for AD-ANCL and supports the use of AFSM or
      CSPalpha aggregation as biomarkers for drug screening purposes.

PMID- 28740223
TI  - Dual functional Phi29 DNA polymerase-triggered exponential rolling circle
      amplification for sequence-specific detection of target DNA embedded in long
      stranded genomic DNA.
AB  - An exonucleolytic digestion-assisted exponential rolling circle amplification
      (RCA) strategy was developed for sensitive and sequence-specific detection of
      target DNA embedded in long-stranded genomic DNA. Herein, Phi29 DNA polymerase
      plays two important roles as exonuclease and polymerase. Long-stranded genomic
      DNAs can be broken into small DNA fragments after ultrasonication. The fragments
      that contain target DNA, hybridize with a linear padlock probe to trigger the
      formation of a circular RCA template. The tails protruding from the 3'-end of the
      target DNA sequences are then digested by the 3' -> 5' exonuclease activity of
      Phi29 DNA polymerase even if they fold into a double-stranded structure. The
      digested DNA fragments can then initiate subsequent RCA reaction. RCA products,
      which are designed to fold into G-quadruplex structures, exponentially accumulate
      when appropriate nicking endonuclease recognition sites are introduced rationally
      into the RCA template. This method is demonstrated to work well for real genomic
      DNA detection using human pathogen Cryptococcus neoformans as a model. In
      addition, this work has two other important discoveries: First, the presence of a
      3'-tail can protect the RCA primer from degradation by Phi29 DNA polymerase.
      Second, 3' -> 5' exonucleolytic activity of Phi29 DNA polymerase can work for
      both single- and double-stranded DNA.

PMID- 28740224
TI  - Depression and Catechol-O-methyltransferase (COMT) genetic variants are
      associated with pain in Parkinson's disease.
AB  - Pain is a distressing symptom of Parkinson disease (PD). We aim to determine
      whether the genetic variants of chronic pain-related genes contribute to pain in
      PD patients. We included 418 PD patients and evaluated pain severity on King's PD
      pain scale. We genotyped rs6267, rs6269, rs4633, rs4818 and rs4680 of COMT,
      rs6746030 of SCN9A, and rs1799971 of OPRM1. In total, 193 participants (46.2%)
      experienced pain. Compared to pain-free PD patients, PD patients with pain had an
      earlier age of onset, longer disease duration, and higher depression and motor
      severity (P < 0.01). The frequencies of COMT rs4680 "A" allele were higher in PD
      patients with pain than those without pain (46.1% vs. 31.1%, P < 0.01). Pain
      severity was significantly associated with disease duration (P = 0.02), and COMT
      rs6267 T allele (P < 0.01). We stratified PD by status of depression and the
      association between COMT rs6267 "GT" genotype and pain severity remained
      significant (P < 0.01). Furthermore, pain severity was significantly higher in
      participants having COMT rs4680 "GG" and "GA" genpotypes than those having "AA"
      genotype (P = 0.04). We concluded that depression and COMT rs4680 "GG" and "GA"
      genotypes and COMT rs6267 "GT" genotype contribute to pain in PD patients.

PMID- 28740225
TI  - Clinical Antibiotic-resistant Acinetobacter baumannii Strains with Higher
      Susceptibility to Environmental Phages than Antibiotic-sensitive Strains.
AB  - Antibiotic-resistant Acinetobacter baumannii is associated with nosocomial
      infections worldwide. Here, we used clinically isolated A. baumannii strains as
      models to demonstrate whether antibiotic resistance is correlated with an
      increased susceptibility to bacteriophages. In this study, 24 active phages
      capable of infecting A. baumannii were isolated from various environments, and
      the susceptibilities of both antibiotic-sensitive and antibiotic-resistant
      strains of A. baumannii to different phages were compared. In our study, a total
      of 403 clinically isolated A. baumannii strains were identified. On average, the
      phage infection percentage of the antibiotic-resistant A. baumannii strains was
      84% (from 81-86%), whereas the infection percentage in the antibiotic-sensitive
      A. baumannii strains was only 56.5% (from 49-64%). In addition, the risk of phage
      infection for A. baumannii was significantly increased in the strains that were
      resistant to at least four antibiotics and exhibited a dose-dependent response (p
      trend < 0.0001). Among all of the A. baumannii isolates, 75.6% were phage
      typeable. The results of phage typing might also reveal the antibiotic-resistant
      profiles of clinical A. baumannii strains. In conclusion, phage susceptibility
      represents an evolutionary trade-off in A. baumannii strains that show
      adaptations for antibiotic resistance, particularly in medical environments that
      have high antibiotic use.

PMID- 28740226
TI  - Multicomponent High-throughput Drug Screening via Inkjet Printing to Verify the
      Effect of Immunosuppressive Drugs on Immune T Lymphocytes.
AB  - High-throughput drug screening based on a multi-component array can be used to
      identify a variety of interaction between cells and drugs for suitable purposes.
      The signaling of immune cells is affected by specific proteins, diverse drug
      combinations, and certain immunosuppressive drugs. The effect of a drug on an
      organism is usually complex and involves interactions at multiple levels. Herein,
      we developed a multilayer fabricating system through the high-throughput assembly
      of nanofilms with inkjet printing to investigate the effects of immunosuppressive
      drugs. Immunosuppressive drugs or agents occasionally cause side effects
      depending on drug combinations or a patient's condition. By incorporating various
      drug combinations for understanding interaction between drugs and immune cells,
      we were able to develop an immunological drug screening kit with
      immunosuppressive drugs. Moreover, the ability to control the combination of
      drugs, as well as their potential for high-throughput preparation should be of
      great benefit to the biomedical and bioanalytical field.

PMID- 28740227
TI  - Enhanced figure of merit in nanostructured (Bi,Sb)2Te3 with optimized
      composition, prepared by a straightforward arc-melting procedure.
AB  - Sb-doped Bi2Te3 is known since the 1950s as the best thermoelectric material for
      near-room temperature operation. Improvements in material performance are
      expected from nanostructuring procedures. We present a straightforward and fast
      method to synthesize already nanostructured pellets that show an enhanced ZT due
      to a remarkably low thermal conductivity and unusually high Seebeck coefficient
      for a nominal composition optimized for arc-melting: Bi0.35Sb1.65Te3. We provide
      a detailed structural analysis of the Bi2-xSbxTe3 series (0 <= x <= 2) based on
      neutron powder diffraction as a function of composition and temperature that
      reveals the important role played by atomic vibrations. Arc-melting produces
      layered platelets with less than 50 nm-thick sheets. The low thermal conductivity
      is attributed to the phonon scattering at the grain boundaries of the nanosheets.
      This is a fast and cost-effective production method of highly efficient
      thermoelectric materials.

PMID- 28740228
TI  - Demonstrating an absolute quantum advantage in direct absorption measurement.
AB  - Engineering apparatus that harness quantum theory promises to offer practical
      advantages over current technology. A fundamentally more powerful prospect is
      that such quantum technologies could out-perform any future iteration of their
      classical counterparts, no matter how well the attributes of those classical
      strategies can be improved. Here, for optical direct absorption measurement, we
      experimentally demonstrate such an instance of an absolute advantage per photon
      probe that is exposed to the absorbative sample. We use correlated intensity
      measurements of spontaneous parametric downconversion using a commercially
      available air-cooled CCD, a new estimator for data analysis and a high heralding
      efficiency photon-pair source. We show this enables improvement in the precision
      of measurement, per photon probe, beyond what is achievable with an ideal
      coherent state (a perfect laser) detected with 100% efficient and noiseless
      detection. We see this absolute improvement for up to 50% absorption, with a
      maximum observed factor of improvement of 1.46. This equates to around 32%
      reduction in the total number of photons traversing an optical sample, compared
      to any future direct optical absorption measurement using classical light.

PMID- 28740229
TI  - Connexin hemichannel blockade improves survival of striatal GABA-ergic neurons
      after global cerebral ischaemia in term-equivalent fetal sheep.
AB  - Basal ganglia injury at term remains a major cause of disability, such as
      cerebral palsy. In this study we tested the hypotheses that blockade of
      astrocytic connexin hemichannels with a mimetic peptide would improve survival of
      striatal phenotypic neurons after global cerebral ischaemia in term-equivalent
      fetal sheep, and that neuronal survival would be associated with
      electrophysiological recovery. Fetal sheep (0.85 gestation) were randomly
      assigned to receive a short or long (1 or 25 h) intracerebroventricular infusion
      of a mimetic peptide or vehicle, starting 90 minutes after 30 minutes of cerebral
      ischaemia. Sheep were killed 7 days after ischaemia. Cerebral ischaemia was
      associated with reduced numbers of calbindin-28k, calretinin, parvalbumin and GAD
      positive striatal neurons (P < 0.05 ischaemia + vehicle, n = 6 vs. sham
      ischaemia, n = 6) but not ChAT or nNOS positive neurons. Short infusion of
      peptide (n = 6) did not significantly improve survival of any striatal phenotype.
      Long infusion of peptide (n = 6) was associated with increased survival of
      calbindin-28k, calretinin, parvalbumin and GAD positive neurons (P < 0.05 vs.
      ischaemia + vehicle). Neurophysiological recovery was associated with improved
      survival of calbindin-28k, calretinin and parvalbumin positive striatal neurons
      (P < 0.05 for all). In conclusion, connexin hemichannel blockade after cerebral
      ischaemia in term-equivalent fetal sheep improves survival of striatal GABA-ergic
      neurons.

PMID- 28740230
TI  - NMR analysis reveals significant differences in the plasma metabolic profiles of
      Niemann Pick C1 patients, heterozygous carriers, and healthy controls.
AB  - Niemann-Pick type C1 (NPC1) disease is a rare autosomal recessive,
      neurodegenerative lysosomal storage disorder, which presents with a range of
      clinical phenotypes and hence diagnosis remains a challenge. In view of these
      difficulties, the search for a novel, NPC1-specific biomarker (or set of
      biomarkers) is a topic of much interest. Here we employed high-resolution 1H
      nuclear magnetic resonance spectroscopy coupled with advanced multivariate
      analysis techniques in order to explore and seek differences between blood plasma
      samples acquired from NPC1 (untreated and miglustat treated), heterozygote, and
      healthy control subjects. Using this approach, we were able to identify NPC1
      disease with 91% accuracy confirming that there are significant differences in
      the NMR plasma metabolic profiles of NPC1 patients when compared to healthy
      controls. The discrimination between NPC1 (both miglustat treated and untreated)
      and healthy controls was dominated by lipoprotein triacylglycerol 1H NMR
      resonances and isoleucine. Heterozygote plasma samples displayed also increases
      in the intensities of selected lipoprotein triacylglycerol 1H NMR signals over
      those of healthy controls. The metabolites identified could represent useful
      biomarkers in the future and provide valuable insight in to the underlying
      pathology of NPC1 disease.

PMID- 28740231
TI  - Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen
      activated protein kinase.
AB  - Intestinal epithelial barrier properties are maintained by a junctional complex
      consisting of tight junctions (TJ), adherens junctions (AJ) and desmosomes.
      Desmoglein 2 (Dsg2), an adhesion molecule of desmosomes and the only Dsg isoform
      expressed in enterocytes, is required for epithelial barrier properties and may
      contribute to barrier defects in Crohn's disease. Here, we identified
      extradesmosomal Dsg2 on the surface of polarized enterocytes by Triton
      extraction, confocal microscopy, SIM and STED. Atomic force microscopy (AFM)
      revealed Dsg2-specific binding events along the cell border on the surface of
      enterocytes with a mean unbinding force of around 30pN. Binding events were
      blocked by an inhibitory antibody targeting Dsg2 which under same conditions
      activated p38MAPK but did not reduce cell cohesion. In enterocytes deficient for
      Dsg2, p38MAPK activity was reduced and both barrier integrity and reformation
      were impaired. Dsc2 rescue did not restore p38MAPK activity indicating that Dsg2
      is required. Accordingly, direct activation of p38MAPK in Dsg2-deficient cells
      enhanced barrier reformation demonstrating that Dsg2-mediated activation of
      p38MAPK is crucial for barrier function. Collectively, our data show that Dsg2,
      beside its adhesion function, regulates intestinal barrier function via p38MAPK
      signalling. This is in contrast to keratinocytes and points towards tissue
      specific signalling functions of desmosomal cadherins.

PMID- 28740233
TI  - A receptor dependent-4D QSAR approach to predict the activity of mutated enzymes.
AB  - Screening and selection tools to obtain focused libraries play a key role in
      successfully engineering enzymes of desired qualities. The quality of screening
      depends on efficient assays; however, a focused library generated with a priori
      information plays a major role in effectively identifying the right enzyme. As a
      proof of concept, for the first time, receptor dependent - 4D Quantitative
      Structure Activity Relationship (RD-4D-QSAR) has been implemented to predict
      kinetic properties of an enzyme. The novelty of this study is that the mutated
      enzymes also form a part of the training data set. The mutations were modeled in
      a serine protease and molecular dynamics simulations were conducted to derive
      enzyme-substrate (E-S) conformations. The E-S conformations were enclosed in a
      high resolution grid consisting of 156,250 grid points that stores interaction
      energies to generate QSAR models to predict the enzyme activity. The QSAR
      predictions showed similar results as reported in the kinetic studies with >80%
      specificity and >50% sensitivity revealing that the top ranked models
      unambiguously differentiated enzymes with high and low activity. The interaction
      energy descriptors of the best QSAR model were used to identify residues
      responsible for enzymatic activity and substrate specificity.

PMID- 28740232
TI  - p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which
      modulates autophagosome biogenesis.
AB  - Macroautophagy mediates the selective degradation of proteins and non
      proteinaceous cellular constituents. Here, we show that the N-end rule pathway
      modulates macroautophagy. In this mechanism, the autophagic adapter
      p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1 and type-2 N
      terminal degrons (N-degrons), including arginine (Nt-Arg). Both types of N
      degrons bind its ZZ domain. By employing three-dimensional modeling, we developed
      synthetic ligands to p62 ZZ domain. The binding of Nt-Arg and synthetic ligands
      to ZZ domain facilitates disulfide bond-linked aggregation of p62 and p62
      interaction with LC3, leading to the delivery of p62 and its cargoes to the
      autophagosome. Upon binding to its ligand, p62 acts as a modulator of
      macroautophagy, inducing autophagosome biogenesis. Through these dual functions,
      cells can activate p62 and induce selective autophagy upon the accumulation of
      autophagic cargoes. We also propose that p62 mediates the crosstalk between the
      ubiquitin-proteasome system and autophagy through its binding Nt-Arg and other N
      degrons.Soluble misfolded proteins that fail to be degraded by the ubiquitin
      proteasome system (UPS) are redirected to autophagy via specific adaptors, such
      as p62. Here the authors show that p62 recognises N-degrons in these proteins,
      acting as a N-recognin from the proteolytic N-end rule pathway, and targets these
      cargos to autophagosomal degradation.

PMID- 28740234
TI  - Virgin queen attraction toward males in honey bees.
AB  - Although the honeybee is a crucial agricultural agent and a prominent scientific
      model organism, crucial aspects of its reproductive behaviour are still unknown.
      During the mating season, honeybee males, the drones, gather in congregations 10
      40 m above ground. Converging evidence suggests that drones emit a pheromone that
      can attract other drones, thereby increasing the size of the congregation. Virgin
      queens join the vicinity of the congregation after it has formed, and mate with
      as many as 20 males in mid-air. It is still unclear which sensory cues help
      virgin queens find drone congregations in the first place. Beside visual cues for
      long-range orientation, queens may use olfactory cues. We thus tested virgin
      queens' olfactory orientation on a walking simulator in which they have full
      control over odour stimulation. We show that sexually-mature virgin queens are
      attracted to the odour bouquet from a group of living drones. They are not
      attracted to the bouquet from a group of workers. In addition, non-sexually
      receptive females (workers) of the same age are not attracted to the drone odour
      bouquet. Interpreted in the context of mating, these results may suggest that
      virgin queens use volatile olfactory cues from the drones to find the
      congregations.

PMID- 28740235
TI  - Dendritic optical antennas: scattering properties and fluorescence enhancement.
AB  - With the development of nanotechnologies, researchers have brought the concept of
      antenna to the optical regime for manipulation of nano-scaled light matter
      interactions. Most optical nanoantennas optimize optical function, but are not
      electrically connected. In order to realize functions that require electrical
      addressing, optical nanoantennas that are electrically continuous are desirable.
      In this article, we study the optical response of a type of electrically
      connected nanoantennas, which we propose to call "dendritic" antennas. While they
      are connected, they follow similar antenna hybridization trends to unconnected
      plasmon phased array antennas. The optical resonances supported by this type of
      nanoantennas are mapped both experimentally and theoretically to unravel their
      optical response. Photoluminescence measurements indicate a potential Purcell
      enhancement of more than a factor of 58.

PMID- 28740236
TI  - Reduced expression of the murine HLA-G homolog Qa-2 is associated with
      malignancy, epithelial-mesenchymal transition and stemness in breast cancer
      cells.
AB  - Qa-2 is believed to mediate a protective immune response against cancer; however,
      little is known about the role of Qa-2 in tumorigenesis. Here, we used 4T1 breast
      cancer cells to study the involvement of Qa-2 in tumor progression in a syngeneic
      host. Qa-2 expression was reduced during in vivo tumor growth and in cell lines
      derived from 4T1-induced tumors. Tumor-derived cells elicited an epithelial
      mesenchymal transition associated with upregulation of Zeb1 and Twist1/2 and
      enhanced tumor initiating and invasive capacities. Furthermore, these cells
      showed increased stem characteristics, as demonstrated by upregulation of Hes1,
      Sox2 and Oct3/4, and enrichment of CD44high/CD24median/low cells. Remarkably, Qa
      2 cell-surface expression was excluded from the CD44high/CD24median/low
      subpopulation. Tumor-derived cells showed increased Src activity, and treatment
      of these cells with the Src kinase inhibitor PP2 enhanced Qa-2 but reduced Sox2
      and CD44high/CD24median/low expression levels, suggesting that Src signaling,
      while positively associated with stemness, negatively regulates Qa-2 expression
      in breast cancer. Finally, overexpression of the Qa-2 family member Q7 on the
      cell surface slowed down in vivo tumor growth and reduced the metastatic
      potential of 4T1 cells. These results suggest an anti-malignant role for Qa-2 in
      breast cancer development, which appears to be absent from cancer stem cells.

PMID- 28740237
TI  - AGC family kinase 1 participates in trogocytosis but not in phagocytosis in
      Entamoeba histolytica.
AB  - The protozoan parasite Entamoeba histolytica is the aetiologic agent of
      amoebiasis, an endemic infection in developing countries with considerable
      morbidity and mortality. Recently, trogocytosis has been recognized as the key
      step in amoebic cytolysis and invasion, a paradigm shift in understanding
      pathogenicity of this organism. Here we report that AGC family kinase 1 is
      specifically involved in trogocytosis of live human cells and does not
      participate in phagocytosis of dead cells. Live imaging reveals localization of
      this kinase in the long and thin tunnels formed during trogocytosis but not in
      the trogosomes (endosomes formed after trogocytosis). Silencing of the specific
      gene leads to a defect in CHO cell destruction and trogocytosis while other
      endocytic processes remain unaffected. The results suggest that the trogocytic
      pathway is likely to be different from phagocytosis though many of the steps and
      molecules involved may be common. Entamoeba histolytica can kill host cells by
      trogocytosis, while it ingests dead cells by phagocytosis. Here, Somlata et al.
      show that EhAGCK1, an AGC family kinase, is specifically involved in
      trogocytosis, shedding light on the molecular differences between trogocytosis
      and phagocytosis.

PMID- 28740238
TI  - The resident pathobiont Staphylococcus xylosus in Nfkbiz-deficient skin
      accelerates spontaneous skin inflammation.
AB  - IkappaBzeta, which is encoded by the Nfkbiz gene, is a member of the nuclear
      IkappaB family of proteins that act as transcriptional regulators via association
      with NF-kappaB. Nfkbiz-deficient (Nfkbiz -/-) mice develop spontaneous
      dermatitis; however, the underlying mechanism has yet to be elucidated. In our
      study, we found higher skin pathology scores and more serum IgE antibodies and
      trans-epidermal water loss in Nfkbiz -/- than in Nfkbiz-sufficient (Nfkbiz +/-)
      mice. There was also greater expansion of IFN-gamma-, IL-17A-, and IL-22
      secreting CD4+ T cells and of IL-17A-secreting gammadelta+ T cells in the skin of
      Nfkbiz -/- mice than in with Nfkbiz +/- mice. Pyrosequencing analysis showed
      decreased diversity of resident bacteria and markedly expanded Staphylococcus
      (S.) xylosus in the skin of Nfkbiz -/- mice. Oral administration of antibiotics
      including cephalexin and enrofloxacin ameliorated skin inflammation. Topical
      application of S. xylosus also resulted in the expansion of IL-17A-secreting CD4+
      T cells along with high levels of pro-inflammatory cytokines and chemokines in
      the skin of Nfkbiz -/- mice. The expansion of commensal S. xylosus may be one
      cause of skin dysbiosis in Nfkbiz -/- mice and suggests that the Nfkbiz gene may
      play a regulatory role in the microbiota-skin immunity axis.

PMID- 28740239
TI  - Probing the magnetic profile of diluted magnetic semiconductors using polarized
      neutron reflectivity.
AB  - Room temperature ferromagnetism has been observed in the Cu doped ZnO films
      deposited under an oxygen partial pressure of 10-3 and 10-5 torr on Pt (200
      nm)/Ti (45 nm)/Si (001) substrates using pulsed laser deposition. Due to the
      deposition at relatively high temperature (873 K), Cu and Ti atoms diffuse to the
      surface and interface, which significantly affects the magnetic properties. Depth
      sensitive polarized neutron reflectometry method provides the details of the
      composition and magnetization profiles and shows that an accumulation of Cu on
      the surface leads to an increase in the magnetization near the surface. Our
      results reveal that the presence of the copper at Zn sites induces ferromagnetism
      at room temperature, confirming intrinsic ferromagnetism.

PMID- 28740240
TI  - Predicting the spread of the Asian hornet (Vespa velutina) following its
      incursion into Great Britain.
AB  - The yellow-legged or Asian hornet (Vespa velutina) is native to South-East Asia,
      and is a voracious predator of pollinating insects including honey bees. Since
      its accidental introduction into South-Western France in 2004, V. velutina has
      spread to much of western Europe. The presence of V. velutina in Great Britain
      was first confirmed in September 2016. The likely dynamics following an initial
      incursion are uncertain, especially the risk of continued spread, and the likely
      success of control measures. Here we extrapolate from the situation in France to
      quantify the potential invasion of V. velutina in Great Britain. We find that,
      without control, V. velutina could colonise the British mainland rapidly,
      depending upon how the Asian hornet responds to the colder climate in Britain
      compared to France. The announcement that a second hornet had been discovered in
      Somerset, increases the chance that the invasion first occurred before 2016. We
      therefore consider the likely site of first invasion and the probabilistic
      position of additional founding nests in late 2016 and early 2017. Given the
      potential dispersion of V. velutina, we conclude that vigilance is required over
      a large area to prevent the establishment of this threat to the pollinator
      population.

PMID- 28740241
TI  - Projecting the effects of climate change on Calanus finmarchicus distribution
      within the U.S. Northeast Continental Shelf.
AB  - Calanus finmarchicus is vital to pelagic ecosystems in the North Atlantic Ocean.
      Previous studies suggest the species is vulnerable to the effects of global
      warming, particularly on the Northeast U.S. Shelf, which is in the southern
      portion of its range. In this study, we evaluate an ensemble of six different
      downscaled climate models and a high-resolution global climate model, and create
      a generalized additive model (GAM) to examine how future changes in temperature
      and salinity could affect the distribution and density of C. finmarchicus. By
      2081-2100, we project average C. finmarchicus density will decrease by as much as
      50% under a high greenhouse gas emissions scenario. These decreases are
      particularly pronounced in the spring and summer in the Gulf of Maine and Georges
      Bank. When compared to a high-resolution global climate model, the ensemble
      showed a more uniform change throughout the Northeast U.S. Shelf, while the high
      resolution model showed larger decreases in the Northeast Channel, Shelf Break,
      and Central Gulf of Maine. C. finmarchicus is an important link between primary
      production and higher trophic levels, and the decrease projected here could be
      detrimental to the North Atlantic Right Whale and a host of important fishery
      species.

PMID- 28740242
TI  - A distinction between two instruments measuring dispositional mindfulness and the
      correlations between those measurements and the neuroanatomical structure.
AB  - The most widely used measurements of mindfulness are the Mindful Attention
      Awareness Scale (MAAS) and the Five Facet Mindfulness Questionnaire (FFMQ).
      However, controversies exist regarding the application of these scales.
      Additionally, the neural mechanisms of dispositional mindfulness havebecome a
      topic of interest. In the current study, we used surface-based methodology to
      identify the brain regions underlying individual differences in dispositional
      mindfulness in a large non-clinical sampleand compared the two instruments for
      measuring the dispositional mindfulness. The results indicated that theMAAS
      scores were significantly associated with increased greymatter volumes in the
      right precuneus and the significant association between the precuneus and
      depression symptomatology was mediated by MAAS scores. Regarding the FFMQ, the
      Describing, Nonjudging, and Nonreactivity facets were selectively associated with
      the cortical volume, thickness and surface area of multiple prefrontal regions as
      well as the inferior parietal lobule. Importantly, Describing mediated the
      association between the dorsolateral PFC volume and the cognitive reappraisal
      strategies of emotion regulation. These resultssuggested that the MAASwere mainly
      associated with self-awareness, while the FFMQ facets were selectively involved
      in emotion regulation, attention control and self-awareness. Therefore, this
      study characterized the differences in inter-individual variability between the
      two typical measurements of dispositional mindfulnessand the correlations between
      those measurements and imaging analyses.

PMID- 28740243
TI  - Antisocial rewarding in structured populations.
AB  - Cooperation in collective action dilemmas usually breaks down in the absence of
      additional incentive mechanisms. This tragedy can be escaped if cooperators have
      the possibility to invest in reward funds that are shared exclusively among
      cooperators (prosocial rewarding). Yet, the presence of defectors who do not
      contribute to the public good but do reward themselves (antisocial rewarding)
      deters cooperation in the absence of additional countermeasures. A recent
      simulation study suggests that spatial structure is sufficient to prevent
      antisocial rewarding from deterring cooperation. Here we reinvestigate this issue
      assuming mixed strategies and weak selection on a game-theoretic model of social
      interactions, which we also validate using individual-based simulations. We show
      that increasing reward funds facilitates the maintenance of prosocial rewarding
      but prevents its invasion, and that spatial structure can sometimes select
      against the evolution of prosocial rewarding. Our results suggest that, even in
      spatially structured populations, additional mechanisms are required to prevent
      antisocial rewarding from deterring cooperation in public goods dilemmas.

PMID- 28740244
TI  - Mechanisms and Specificity of Phenazine Biosynthesis Protein PhzF.
AB  - Phenazines are bacterial virulence and survival factors with important roles in
      infectious disease. PhzF catalyzes a key reaction in their biosynthesis by
      isomerizing (2 S,3 S)-2,3-dihydro-3-hydroxy anthranilate (DHHA) in two steps, a
      [1,5]-hydrogen shift followed by tautomerization to an aminoketone. While the
      [1,5]-hydrogen shift requires the conserved glutamate E45, suggesting acid/base
      catalysis, it also shows hallmarks of a sigmatropic rearrangement, namely the
      suprafacial migration of a non-acidic proton. To discriminate these mechanistic
      alternatives, we employed enzyme kinetic measurements and computational methods.
      Quantum mechanics/molecular mechanics (QM/MM) calculations revealed that the
      activation barrier of a proton shuttle mechanism involving E45 is significantly
      lower than that of a sigmatropic [1,5]-hydrogen shift. QM/MM also predicted a
      large kinetic isotope effect, which was indeed observed with deuterated
      substrate. For the tautomerization, QM/MM calculations suggested involvement of
      E45 and an active site water molecule, explaining the observed stereochemistry.
      Because these findings imply that PhzF can act only on a limited substrate
      spectrum, we also investigated the turnover of DHHA derivatives, of which only O
      methyl and O-ethyl DHHA were converted. Together, these data reveal how PhzF
      orchestrates a water-free with a water-dependent step. Its unique mechanism,
      specificity and essential role in phenazine biosynthesis may offer opportunities
      for inhibitor development.

PMID- 28740245
TI  - Fish oil diet may reduce inflammatory levels in the liver of middle-aged rats.
AB  - The impact of dietary soybean oil, lard and fish oil on physiological responses
      in middle age is little studied. In this study, we investigated the changes of
      oxidative stress, inflammatory cytokines, telomere length, and age-related gene
      expression in the liver of middle-aged rats in response to the above three fat
      diets. Male Sprague Dawley rats (12 months old) were fed AIN-93M diets for 3
      months, in which soybean oil was equivalently replaced by lard or fish oil. As
      compared to the lard diet, intake of fish oil diet significantly decreased body
      weight gain, white blood cell count, and levels of hepatic triacylglycerol, total
      cholesterol, fat accumulation, low-density lipoprotein, oxidative stress and
      inflammatory cytokines (P < 0.05), but increased telomere length (P < 0.05). On
      the other hand, lard diet and soybean oil diet showed great similarity in the
      above variables. PCR array analysis further indicated that fish oil diet
      significantly down-regulated gene expression related to inflammatory response,
      apoptosis, DNA binding, proteostasis and telomere attrition. Differentially
      expressed genes were enriched in the complement and coagulation cascades
      pathways. Such physiological and molecular responses could be due to different
      fatty acid composition in fish oil, lard and soybean oil.

PMID- 28740246
TI  - Route to sustainable lithium-sulfur batteries with high practical capacity
      through a fluorine free polysulfide catholyte and self-standing Carbon Nanofiber
      membranes.
AB  - We report on a new strategy to improve the capacity, reduce the manufacturing
      costs and increase the sustainability of Lithium-Sulfur (LiS) batteries. It is
      based on a semi-liquid cathode composed of a Li2S8 polysulphide catholyte and a
      binder-free carbon nanofiber membrane with tailored morphology. The polysulphides
      in the catholyte have the dual role of active material and providing Li+
      conduction, i.e. no traditional Li-salt is used in this cell. The cell is able to
      deliver an areal capacity as high as 7 mAh cm-2, twice than that of commercial
      Lithium-ion batteries (LiBs) and 2-4 times higher than that of state-of-the-art
      LiS cells. In addition, the battery concept has an improved sustainability from a
      material point of view by being mainly based on sulfur and carbon and being
      completely fluorine-free, no fluorinated salt or binders are used, and has
      potential for upscaling and competitive price. The combination of these
      properties makes the semi-liquid LiS cell here reported a very promising new
      concept for practical large-scale energy storage applications.

PMID- 28740247
TI  - Inactivation Mechanism of Escherichia coli Induced by Slightly Acidic
      Electrolyzed Water.
AB  - Foodborne disease outbreak caused by food microbiological contamination is a
      serious public health problem. Slightly acidic electrolyzed water (SAEW), a new
      ultra-high effect and wide-spectrum disinfectant that is colourless, odourless,
      and harmless to humans and the environment, is directly used on food surfaces in
      Japan and America. However, the underlying inactivation mechanism remains
      unknown. In this study, biochemical and cellular changes were observed to
      investigate the bactericidal mechanism of SAEW against Escherichia coli (E.
      coli). The results indicated that SAEW with a pH of 6.40, an oxidation-reduction
      potential (ORP) of 910 mV, an available chlorine concentration (ACC) of 60 mg/L,
      and a volume ratio of 20:1, produced the most effective sterilization action. A
      fluorescence-based live-dead assay was further used to demonstrate the sterilized
      effect and the cell esterase activity damage caused by SAEW. During the
      observation period, within 10 min, the cell morphology changed, which was
      characterized by cell expansion, cell elongation and increased membrane
      permeability. Meanwhile, reactive oxygen substances (ROS) were released in the
      bacterial cells. E. coli inactivation and apoptosis induced by SAEW were
      observed. Our findings illustrate that the bactericidal effects of SAEW against
      E. coli occurred through cellular and biochemical mechanisms of cell necrosis and
      apoptosis.

PMID- 28740248
TI  - Associations of Coffee, Diet Drinks, and Non-Nutritive Sweetener Use with
      Depression among Populations in Eastern Canada.
AB  - Consumption of coffee and diet drinks and the use of non-nutritive sweeteners is
      commonplace worldwide. We conducted a cross-sectional analysis to investigate the
      associations between coffee consumption and non-nutritive sweetener use and
      depression among populations in Atlantic Canada. During 2009 to 2013, we
      recruited 18838 participants aged 35-69 years (5854 men and 12984 women) for the
      baseline survey of the Atlantic Partnership for Tomorrow's Health cohort study.
      Coffee consumption, sweetener use, and major depression were assessed using a set
      of standardized questionnaires. We utilized multiple logistic regression models
      to assess the associations of coffee drinking and non-nutritive sweetener use
      with major depression. Compared with non-coffee drinkers, female participants who
      drank coffee >=4 cups/day had an odds ratio of 1.38 (95% confidence interval,
      1.15-1.64) for major depression with adjustment for sociodemographic and
      behavioral factors, chronic disease status, and body mass index. We found a
      significant association between depression and consumption of sweeteners and diet
      drinks, which was more apparent among women than men. We conclude that heavy
      coffee drinking and non-nutritive sweetener use were associated with depression
      among populations in Atlantic Canada. Further studies are warranted to
      investigate the underlying biological mechanisms.

PMID- 28740249
TI  - Neanderthal-Derived Genetic Variation Shapes Modern Human Cranium and Brain.
AB  - Before their disappearance from the fossil record approximately 40,000 years ago,
      Neanderthals, the ancient hominin lineage most closely related to modern humans,
      interbred with ancestors of present-day humans. The legacy of this gene flow
      persists through Neanderthal-derived variants that survive in modern human DNA;
      however, the neural implications of this inheritance are uncertain. Here, using
      MRI in a large cohort of healthy individuals of European-descent, we show that
      the amount of Neanderthal-originating polymorphism carried in living humans is
      related to cranial and brain morphology. First, as a validation of our approach,
      we demonstrate that a greater load of Neanderthal-derived genetic variants
      (higher "NeanderScore") is associated with skull shapes resembling those of known
      Neanderthal cranial remains, particularly in occipital and parietal bones. Next,
      we demonstrate convergent NeanderScore-related findings in the brain (measured by
      gray- and white-matter volume, sulcal depth, and gyrification index) that
      localize to the visual cortex and intraparietal sulcus. This work provides
      insights into ancestral human neurobiology and suggests that Neanderthal-derived
      genetic variation is neurologically functional in the contemporary population.

PMID- 28740250
TI  - Green tide development associated with submarine groundwater discharge in a
      coastal harbor, Jeju, Korea.
AB  - We measured the magnitude of submarine fresh groundwater discharge (SFGD) and
      associated nutrient inputs to Jocheon harbor, on Jeju Island, Korea, during four
      sampling periods, in order to determine the link between SFGD and Ulva sp. green
      tide development. Good correlations among salinity, 222Rn, and dissolved
      inorganic nitrogen (DIN) in harbor seawater suggest that SFGD is the major source
      of DIN and fresh water since there are no surface runoffs. Using a 222Rn mass
      balance model, SFGD to the harbor was estimated to be 5.8 +/- 2.3 * 104 m3 d-1.
      The DIN inputs through SFGD enhanced DIN concentrations in harbor seawater
      approximately 10-fold of those in the open-ocean (outer harbor) seawater. Results
      from mesocosm experiments showed that the growth rate of U. pertusa increased by
      160% on average due to the enhanced DIN concentrations (from 1 to 24 uM) through
      SFGD in this harbor. Thus, we conclude that DIN inputs through SFGD cause the
      green tide development in Jocheon harbor and perhaps in other green tide regions
      where river inputs are absent.

PMID- 28740251
TI  - Shapes of distal tibiofibular syndesmosis are associated with risk of recurrent
      lateral ankle sprains.
AB  - Distal tibiofibular syndesmosis (DTS) has wide anatomic variability in depth of
      incisura fibularis and shape of tibial tubercles. We designed a 3-year
      prospective cohort study of 300 young physical training soldiers in an Army
      Physical Fitness School. Ankle computed tomography (CT) scans showed that 56% of
      the incisura fibularis were a "C" shape, 25% were a "1" shape, and 19% were a "G"
      shape. Furthermore, we invited a randomly selected subcohort of 6 participants in
      each shape of DTS to undergo a three-dimensional (3D) laser scanning. The "1"
      shape group showed widest displacement range of the DTS in the y-axis, along with
      the range of motion (ROM) on the position more than 20 degrees  of the ankle
      dorsiflexion, inversion and eversion. During the 3-year study period, 23
      participants experienced recurrent lateral ankle sprains. 7 cases of the incisura
      fibularis were "C" shape, 13 cases were "1" shape, and 3 cases were "G" shape.
      The "1" shape showed highest risk among the three shapes in incident recurrent
      lateral ankle sprains. We propose that it is possible to classify shapes of DTS
      according to the shapes of incisura fibularis, and people with "1" shape may have
      more risk of recurrent lateral ankle sprains.

PMID- 28740252
TI  - Decelerated neurodegeneration after intravitreal injection of alpha-synuclein
      antibodies in a glaucoma animal model.
AB  - Although elevated intraocular pressure (IOP) remains the major risk factor in
      glaucoma, neurodegenerative processes continue despite effective IOP lowering.
      Altered alpha-synuclein antibody (Abs) levels have been reported to play a
      crucial role. This study aimed at identifying whether alpha-synuclein Abs are
      capable to decelerate neuronal decay while providing insights into proteomic
      changes. Four groups of Sprague Dawley rats received episcleral vein occlusion:
      (1) CTRL, no intravitreal injection, n = 6, (2) CTRL IgG, intravitreal injection
      of unspecific IgG, n = 5, (3) Buffer, intravitreal injection of buffer, n = 6,
      (4), alpha-synuclein Ab, intravitreal injection of alpha-synuclein Ab, n = 5. IOP
      and retinal nerve fiber layer thickness (RNFLT) were monitored and
      immunohistochemistry, microarray and proteomic analysis were performed. RNFLT was
      reduced in CTRL, CTRL IgG and Buffer group (all p < 0.01) and alpha-synuclein Ab
      group (p = 0.17). Axon and RGC density showed an increased neurodegeneration in
      CTRL, CTRL IgG and Buffer group (all p < 0.01) and increased neuronal survival in
      alpha-synuclein Ab group (p = 0.38 and 0.06, respectively) compared with fellow
      eyes. Proteomic analysis revealed alterations of cofilin 1 and superoxide
      dismutase 1 expression. This data indicate that alpha-synuclein Ab might
      indirectly modulate the actin cytoskeleton organization and negatively regulate
      apoptotic processes via cofilin 1 and superoxide dismutase 1.

PMID- 28740253
TI  - Effects of Transgenic Rice Infected with SRBSDV on Bt expression and the
      Ecological Fitness of Non-vector Brown Planthopper Nilaparvata lugens.
AB  - The susceptibility of rice lines, T1C-19, T2A-1, and MH63 to SRBSDV infection are
      similar and the contents of cry protein in T2A-1 and T1C-19 do not change
      significantly. The survival rates of BPH nymphs feeding on SRBSDV-infected T1C
      19, Bt T2A-1, or MH63 rice plants were not significantly different. The
      developmental stages of female BPH fed on T1C-19 plants infected with SRBSDV were
      significantly shorter than those fed on uninfected rice, while the males showed
      no significant difference. The duration of BPH feeding on SRBSDV-infected T2A-1
      and MH63 also showed no significant difference in comparison with the respective
      control groups. Longevities of BPH adults feeding on SRBSDV-infected T1C-19, T2A
      1 or MH63 were also not significant. However, the longevity of male adult BPH
      feeding on un-infected MH63 was significantly reduced in comparison with that of
      adult males feeding on un-infected T1C-19 and T2A-1 rice. In addition, the
      different rice lines and the rice plants infected and uninfected with SRBSDV did
      not significantly affect the sex ratio, female body weight, longevity, fecundity,
      or egg hatchability of BPH. In general, transgenic Bt rice infected with SRBSDV
      had little effect on the ecological adaptability of BPH.

PMID- 28740254
TI  - The Role of Inflammation in beta-cell Dedifferentiation.
AB  - Chronic inflammation impairs insulin secretion and sensitivity. beta-cell
      dedifferentiation has recently been proposed as a mechanism underlying beta-cell
      failure in T2D. Yet the effect of inflammation on beta-cell identity in T2D has
      not been studied. Therefore, we investigated whether pro-inflammatory cytokines
      induce beta-cell dedifferentiation and whether anti-inflammatory treatments
      improve insulin secretion via beta-cell redifferentiation. We observed that IL
      1beta, IL-6 and TNFalpha promote beta-cell dedifferentiation in cultured human
      and mouse islets, with IL-1beta being the most potent one of them. In particular,
      beta-cell identity maintaining transcription factor Foxo1 was downregulated upon
      IL-1beta exposure. In vivo, anti-IL-1beta, anti-TNFalpha or NF-kB inhibiting
      sodium salicylate treatment improved insulin secretion of isolated islets.
      However, only TNFalpha antagonism partially prevented the loss of beta-cell
      identity gene expression. Finally, the combination of IL-1beta and TNFalpha
      antagonism improved insulin secretion of ex vivo isolated islets in a synergistic
      manner. Thus, while inflammation triggered beta-cell dedifferentiation and
      dysfunction in vitro, this mechanism seems to be only partly responsible for the
      observed in vivo improvements in insulin secretion.

PMID- 28740255
TI  - Untangling the model muddle: Empirical tumour growth in Tasmanian devil facial
      tumour disease.
AB  - A pressing and unresolved topic in cancer research is how tumours grow in the
      absence of treatment. Despite advances in cancer biology, therapeutic and
      diagnostic technologies, there is limited knowledge regarding the fundamental
      growth and developmental patterns in solid tumours. In this ten year study, we
      estimated growth curves in Tasmanian devil facial tumours, a clonal transmissible
      cancer, in males and females with two different karyotypes (diploid, tetraploid)
      and facial locations (mucosal, dermal), using established differential equation
      models and model selection. Logistic growth was the most parsimonious model for
      diploid, tetraploid and mucosal tumours, with less model certainty for dermal
      tumours. Estimates of daily proportional tumour growth rate per day (95% Bayesian
      CIs) varied with ploidy and location [diploid 0.016 (0.014-0.020), tetraploid
      0.026 (0.020-0.033), mucosal 0.013 (0.011-0.015), dermal 0.020 (0.016-0.024)].
      Final tumour size (cm3) also varied, particularly the upper credible interval
      owing to host mortality as tumours approached maximum volume [diploid 364 (136
      2,475), tetraploid 172 (100-305), dermal 226 (134-471)]. To our knowledge, these
      are the first empirical estimates of tumour growth in the absence of treatment in
      a wild population. Through this animal-cancer system our findings may enhance
      understanding of how tumour properties interact with growth dynamics in other
      types of cancer.

PMID- 28740256
TI  - Influence of doxorubicin on model cell membrane properties: insights from in
      vitro and in silico studies.
AB  - Despite doxorubicin being commonly used in chemotherapy there still remain
      significant holes in our knowledge regarding its delivery efficacy and an
      observed resistance mechanism that is postulated to involve the cell membrane.
      One possible mechanism is the efflux by protein P-gp, which is found
      predominantly in cholesterol enriched domains. Thereby, a hypothesis for the
      vulnerability of doxorubicin to efflux through P-gp is its enhanced affinity for
      the ordered cholesterol rich regions of the plasma membrane. Thus, we have
      studied doxorubicin's interaction with model membranes in a cholesterol rich,
      ordered environment and in liquid-disordered cholesterol poor environment. We
      have combined three separate experimental protocols: UV-Vis spectrophotometry,
      fluorescence quenching and steady-state anisotropy and computational molecular
      dynamics modeling. Our results show that the presence of cholesterol induces a
      change in membrane structure and doesn't impair doxorubicin's membrane
      partitioning, but reduces drug's influence on membrane fluidity without directly
      interacting with it. It is thus possible that the resistance mechanism that
      lowers the efficacy of doxorubicin, results from an increased density in membrane
      regions where the efflux proteins are present. This work represents a successful
      approach, combining experimental and computational studies of membrane based
      systems to unveil the behavior of drugs and candidate drug molecules.

PMID- 28740257
TI  - Non-destructive detection of cross-sectional strain and defect structure in an
      individual Ag five-fold twinned nanowire by 3D electron diffraction mapping.
AB  - Coherent x-ray diffraction investigations on Ag five-fold twinned nanowires
      (FTNWs) have drawn controversial conclusions concerning whether the intrinsic
      7.35 degrees  angular gap could be compensated homogeneously through phase
      transformation or inhomogeneously by forming disclination strain field. In those
      studies, the x-ray techniques only provided an ensemble average of the structural
      information from all the Ag nanowires. Here, using three-dimensional (3D)
      electron diffraction mapping approach, we non-destructively explore the cross
      sectional strain and the related strain-relief defect structures of an individual
      Ag FTNW with diameter about 30 nm. The quantitative analysis of the fine
      structure of intensity distribution combining with kinematic electron diffraction
      simulation confirms that for such a Ag FTNW, the intrinsic 7.35 degrees  angular
      deficiency results in an inhomogeneous strain field within each single
      crystalline segment consistent with the disclination model of stress-relief.
      Moreover, the five crystalline segments are found to be strained differently.
      Modeling analysis in combination with system energy calculation further indicates
      that the elastic strain energy within some crystalline segments, could be
      partially relieved by the creation of stacking fault layers near the twin
      boundaries. Our study demonstrates that 3D electron diffraction mapping is a
      powerful tool for the cross-sectional strain analysis of complex 1D
      nanostructures.

PMID- 28740258
TI  - Mechanically stable fibrin scaffolds promote viability and induce neurite
      outgrowth in neural aggregates derived from human induced pluripotent stem cells.
AB  - Recent work demonstrated that 3D fibrin scaffolds function as an effective
      substrate for engineering tissues from pluripotent stem cells. However, the rapid
      degradation rate of fibrin remains a major limitation when differentiating human
      pluripotent stem cells for tissue engineering applications. The addition of
      crosslinking agents, such as genipin, during the polymerization process increases
      scaffold stability while decreasing the degradation rate of fibrin. Genipin
      crosslinking alters the physical characteristics of the fibrin scaffolds, which
      influences the behaviour of the differentiating cells seeded inside. It also
      possesses neuritogenic and neuroprotective properties, making it particularly
      attractive for engineering neural tissue from pluripotent stem cells. Here we
      show that genipin enhances neuronal differentiation of neural progenitors derived
      from human induced pluripotent stem cells (hiPSCs) in 2D culture and genipin
      concentration influences the morphological and mechanical properties of 3D fibrin
      scaffolds. These mechanically stable genipin-crosslinked fibrin scaffolds support
      hiPSC-derived neural aggregates and induce neurite outgrowth while remaining
      intact for 2 weeks as opposed to 5 days for unmodified fibrin scaffolds.

PMID- 28740259
TI  - Proteinuria Detected by Urine Dipstick Test as a Risk Factor for Atrial
      Fibrillation: A Nationwide Population-Based Study.
AB  - Proteinuria is one of the well-known risk factors for cardiovascular disease.
      However the impact of proteinuria on the incidence of atrial fibrillation (AF) is
      unclear. In this study, we investigated the association between proteinuria
      detected using urine dipstick test and the risk of AF. A total of 18,201,275
      individuals were analyzed, who had no prior AF and had received biennial health
      checkups provided by the National Health Insurance Service between 2005 and 2008
      in Korea. Incidences of AF were ascertained through the end of 2015. During a
      mean follow-up of 9.6 years, a total of 324,764 (1.8%) developed AF (1.86 per
      1,000 person-years). In Cox regression models, proteinuria was associated with an
      increased risk of AF: adjusted HR and 95% CI of AF occurrence were 1.13 (1.10
      1.16), 1.34 (1.31-1.38), 1.53 (1.48-1.58), 1.82 (1.71-1.94), and 1.86 (1.61-2.16)
      in individuals with trace, 1+, 2+, 3+, and 4+ proteinuria, respectively, compared
      with those without proteinuria. The result was consistent even after additional
      adjustment for estimated glomerular filtration rate. In addition, the risk of AF
      further increased or decreased according to the follow-up dipstick test results.
      Thus, proteinuria measured with a dipstick test might be considered a potent risk
      factor for AF development.

PMID- 28740260
TI  - Richer gut microbiota with distinct metabolic profile in HIV infected Elite
      Controllers.
AB  - Gut microbiota dysbiosis features progressive HIV infection and is a potential
      target for intervention. Herein, we explored the microbiome of 16 elite
      controllers (EC), 32 antiretroviral therapy naive progressors and 16 HIV negative
      controls. We found that the number of observed genera and richness indices in
      fecal microbiota were significantly higher in EC versus naive. Genera
      Succinivibrio, Sutterella, Rhizobium, Delftia, Anaerofilum and Oscillospira were
      more abundant in EC, whereas Blautia and Anaerostipes were depleted.
      Additionally, carbohydrate metabolism and secondary bile acid synthesis pathway
      related genes were less represented in EC. Conversely, fatty acid metabolism,
      PPAR-signalling and lipid biosynthesis proteins pathways were enriched in EC vs
      naive. The kynurenine pathway of tryptophan metabolism was altered during
      progressive HIV infection, and inversely associated with microbiota richness. In
      conclusion, EC have richer gut microbiota than untreated HIV patients, with
      unique bacterial signatures and a distinct metabolic profile which may contribute
      to control of HIV.

PMID- 28740261
TI  - Sustained efficacy of closed loop electrical stimulation for long-term treatment
      of absence epilepsy in rats.
AB  - Closed-loop brain stimulation is a promising alternative to treat drug-resistant
      epilepsies. In contrast to optogenetic interventions, transcranial electrical
      stimulation (TES) does not require cellular modification of neurons to be
      effective, and it is less invasive compared to deep brain stimulation.
      Furthermore, on-demand TES of targeted brain regions allows the potential for
      normal function of these networks during interictal periods, a possibility that
      is eliminated by resective surgical treatment approaches. To further explore the
      translation of closed-loop TES for treatment of epilepsy, we show here for the
      first time that unsupervised closed-loop TES in rats can consistently interrupt
      seizures for 6 weeks and has the potential to control seizure activity up to 4
      months (longest periods examined). On-demand TES significantly reduced the time
      spent in seizure and the individual seizure duration, although significantly
      higher seizure rate was observed during the treatment. The 6 week long
      stimulation had no residual adverse effects on the electrophysiologic
      characteristics of the brain after the termination of the treatment and did not
      induce glial remodelling in the brain. Our findings demonstrate the safety and
      effectiveness of minimally invasive, potentially lifelong TES treatment of
      epilepsy either alone or as a complement to drug treatments.

PMID- 28740262
TI  - Heterogeneity of neuroblastoma cell identity defined by transcriptional
      circuitries.
AB  - Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived
      from multipotent neural crest cells (NCCs). To define core regulatory circuitries
      (CRCs) controlling the gene expression program of neuroblastoma, we established
      and analyzed the neuroblastoma super-enhancer landscape. We discovered three
      types of identity in neuroblastoma cell lines: a sympathetic noradrenergic
      identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3
      transcription factors (TFs); an NCC-like identity, driven by a CRC module
      containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell
      level. Treatment of the mixed type with chemotherapeutic agents resulted in
      enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq.
      Functional studies demonstrated dependency of neuroblastoma with noradrenergic
      identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary
      tumors express TFs from the noradrenergic and NCC-like modules. Our data
      demonstrate a previously unknown aspect of tumor heterogeneity relevant for
      neuroblastoma treatment strategies.

PMID- 28740263
TI  - A gene encoding maize caffeoyl-CoA O-methyltransferase confers quantitative
      resistance to multiple pathogens.
AB  - Alleles that confer multiple disease resistance (MDR) are valuable in crop
      improvement, although the molecular mechanisms underlying their functions remain
      largely unknown. A quantitative trait locus, qMdr9.02, associated with resistance
      to three important foliar maize diseases-southern leaf blight, gray leaf spot and
      northern leaf blight-has been identified on maize chromosome 9. Through fine
      mapping, association analysis, expression analysis, insertional mutagenesis and
      transgenic validation, we demonstrate that ZmCCoAOMT2, which encodes a caffeoyl
      CoA O-methyltransferase associated with the phenylpropanoid pathway and lignin
      production, is the gene within qMdr9.02 conferring quantitative resistance to
      both southern leaf blight and gray leaf spot. We suggest that resistance might be
      caused by allelic variation at the level of both gene expression and amino acid
      sequence, thus resulting in differences in levels of lignin and other metabolites
      of the phenylpropanoid pathway and regulation of programmed cell death.

PMID- 28740264
TI  - PRDM15 safeguards naive pluripotency by transcriptionally regulating WNT and MAPK
      ERK signaling.
AB  - The transcriptional network acting downstream of LIF, WNT and MAPK-ERK to
      stabilize mouse embryonic stem cells (ESCs) in their naive state has been
      extensively characterized. However, the upstream factors regulating these three
      signaling pathways remain largely uncharted. PR-domain-containing proteins
      (PRDMs) are zinc-finger sequence-specific chromatin factors that have essential
      roles in embryonic development and cell fate decisions. Here we characterize the
      transcriptional regulator PRDM15, which acts independently of PRDM14 to regulate
      the naive state of mouse ESCs. Mechanistically, PRDM15 modulates WNT and MAPK-ERK
      signaling by directly promoting the expression of Rspo1 (R-spondin1) and Spry1
      (Sprouty1). Consistent with these findings, CRISPR-Cas9-mediated disruption of
      PRDM15-binding sites in the Rspo1 and Spry1 promoters recapitulates PRDM15
      depletion, both in terms of local chromatin organization and the transcriptional
      modulation of these genes. Collectively, our findings uncover an essential role
      for PRDM15 as a chromatin factor that modulates the transcription of upstream
      regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency.

PMID- 28740265
TI  - The Relationship Between Dental Trauma, Anxiety and Aggression Behavior in 7 to14
      Year old Children in Kosovo.
AB  - BACKGROUND AND AIM: Dental fear has a negative impact on the treatment outcomes.
      The aim of this study was to evaluate dental anxiety among children with
      different measurement scales, with the aim of getting more precise and thorough
      estimations, as well as correlation between anxiety scale and aggression scale in
      children with/or without dental trauma. MATERIAL AND METHODS: The study
      population include 254 children's experience with dental trauma (59.1% male), and
      251 children without dental trauma (46.6% male), between 7 and 14 years old, and
      their respective parents were evaluated during 2015-2016. Psychometric measures
      used for this purpose included several questionnaires. The result was tested with
      the X2 test, Student's t-test, one-way ANOVA, and Pearson's correlation
      coefficient. The Cronbach alpha was used to check the reliability and validity of
      the measures. The predetermined significance levels were set at 0.05. RESULTS:
      All used test has satisfactory reliability and validity of the scale. The mean
      anxiety score was significantly higher in children with dental trauma. The
      children with dental trauma had a higher mean aggression scale (OAS). The girls
      had significantly higher mean anxiety score than boys in all used questionnaires.
      The mean aggression score was significantly higher for boys than girls in both
      compared groups (p<0.001). The Odds of the aggressive behavior in children with
      dental trauma decrease for 0.95 when the value of the mean DVSS-SV scale is
      increased by one units, and increase for 1.04 when the means anxiety score
      increased by one units. CONCLUSION: The mean anxiety score was significantly
      higher in children with dental trauma, as well as the girls and children who are
      more afraid of medical interventions (CMFQ). Also the children with dental
      trauma, and boys had a higher mean aggression scale (OAS).?Significant
      correlation was found between dental anxiety level and aggressive behavior of
      children's. The odds of the aggressive behavior increased with increasing of mean
      score of each anxiety measurement scale, but not significantly, except for S-DAI
      score.

PMID- 28740266
TI  - Reproducibility of Centric Relation Techniques by means of Condyle Position
      Analysis.
AB  - PURPOSE: The aim of this study was to determine the reproducibility of clinical
      centric relation (CR) registration techniques (bimanual manipulation, chin point
      guidance and Roth's method) by means of condyle position analysis. MATERIAL AND
      METHODS: Thirty two fully dentate asymptomatic subjects (16 female and 16 male)
      with normal occlusal relations (Angle class I) participated in the study (mean
      age, 22.6 +/- 4.7 years). The mandibular position indicator (MPI) was used to
      analyze the three-dimensional (anteroposterior (DeltaX), superoinferior (DeltaZ),
      mediolateral (DeltaY)) condylar shift generated by the difference between the
      centric relation position (CR) and the maximal intercuspation position (MI)
      observed in dental arches. RESULTS: The mean value and standard deviation of
      three-dimensional condylar shift of the tested clinical CR techniques was 0.19 +/
      0.34 mm. Significant differences within the tested clinical CR registration
      techniques were found for anteroposterior condylar shift on the right side
      posterior (Delta Xrp; P <= 0.012); and superoinferior condylar shift on the left
      side inferior (Delta Zli; P <= 0.011), whereas between the tested CR registration
      techniques were found for anteroposterior shift on the right side posterior
      (DeltaXrp, P <= 0.037) and superoinferior shift on the right side inferior
      (DeltaZri, P <= 0.004), on the left side inferior (DeltaZli, P <= 0.005) and on
      the left side superior (DeltaZls, P <= 0.007). CONCLUSION: Bimanual manipulation,
      chin point guidance and Roth's method are clinical CR registration techniques of
      equal accuracy and reproducibility in asymptomatic subjects with normal occlusal
      relationship.

PMID- 28740267
TI  - Assessment of esthetic characteristics of the teeth and surrounding anatomical
      structures.
AB  - PURPOSE: To determine the differences in the perception of aesthetic
      characteristics of the front teeth which include anatomic variations, appearance
      of the gums and dental arches, smiles and the lower third of the face between
      three groups of assessors. MATERIALS AND METHODS: The study included 60 patients
      with permanent fully toothed dentition with no prosthetic work done and with
      Angle class I, whose lower third of the face was photographed while smiling.
      Collected photos were then assessed by people of the general population (21),
      graduate doctors of dental medicine (20) and specialists in dental prosthetics
      (20) using a modified OAS questionnaire (Orofacial aesthetic scale). RESULTS:
      General population assessors gave weakest scores to the appearance of teeth,
      tooth color and appearance of the dental arches, and they gave highest scores to
      the appearance of the gums. Specialists in dental prosthetics gave top scores (p
      <0.01) for the shape and color of teeth, the appearance of the dental arches and
      lips and general appearance of the lower third of the face, and gave the worst
      scores for the appearance of the gums (p <0.01). Male assessors and people aged
      36-55 are the least critical in assessing the shape and the color of teeth,
      appearance of the arches and lips, and the general appearance of the lower third
      of the face. In assessing the gums the most tolerant assessors are patients over
      the age of 55 (p<0.01). CONCLUSION: Considering the age and gender it can be
      concluded that all the criteria contribute to the assessment of the aesthetics of
      the teeth and surrounding structures. The results of this study may help in the
      planning of dental prosthetics procedures.

PMID- 28740268
TI  - The Association between Periodontal Disease and Preterm Low Birthweight in
      Kosovo.
AB  - OBJECTIVE: Periodontal diseases have a high prevalence worldwide. Existing
      evidence support the concept that gingivitis and periodontitis are potentially
      infectious and they present inflammatory reservoirs that can be threatening to
      the fetoplacental unit. The objective of this study was to compare the
      periodontal status between women with normal delivery and those with preterm low
      birthweight delivery. MATERIALS AND METHODS: This study included 200 postpartum
      women whose periodontal and obstetrical parameters were taken. The periodontal
      condition was assessed bedside according to the modified criteria established by
      Machtei, while the birthweight and gestational age were assessed according to the
      World Health Organization criteria. RESULTS: Women with periodontitis are
      statistically at 3.2 times higher risk to deliver a child with low weight, and at
      3.4 times higher risk to deliver preterm, compared to women without
      periodontitis. The women with preterm low-birthweight babies had deeper
      periodontal pockets (2.49mm +/- 0.49mm) than women with normal delivery (2.26mm
      +/- 0.49mm). CONCLUSIONS: Periodontal disease in pregnant women with a reservoir
      of organisms and their products can be considered a risk factor for adverse
      pregnancy outcome.

PMID- 28740269
TI  - Frequency, Context and Characteristics of Smile Used in Advertising.
AB  - OBJECTIVE: The images of smiling people are omnipresent in marketing. Frequency,
      smile characteristics, context of the smile and target audience in newspaper
      advertisements were points of interest of this study. MATERIAL AND METHODS: Four
      examiners analyzed 600 advertisements from 46 European magazines and newspapers
      by using content and framing analysis. Twenty items of the analysis form the
      presence of people, smile characteristics, context of smile use, impression of
      success and health, and targeted audience. The chi-square test was used in
      statistical analysis. RESULTS: People were present in over 70% of the newspapers
      advertisements, and almost 80% of them were smiling, relating the product or
      service with positive context more often than with neutral or negative context
      (p<0.001). The advertisements with smile targeted the adults more frequently
      (70.6%) and adolescents (33.6%), and less often the elderly (22.2%) and children
      (4.2%); women (45.9%) or both genders (29.2%) were targeted more often than
      solely men (2.6%). Smile mostly filled out one quarter of the size of the entire
      advertisement (97%), equally spontaneous and posed smiles were used. In 82% of
      cases teeth were visible during smile, and buccal corridors were present in 39%
      of them. CONCLUSIONS: Smile is often used in newspaper advertisements, mostly
      targeting adult women, and providing the context of positive emotions. Most
      people will show teeth when they smile. Parameters of micro smile esthetics are
      not in the focus of an advertisement.

PMID- 28740270
TI  - The Significance of Brain Transcranial Sonography in Burning Mouth Syndrome: a
      Pilot Study.
AB  - OBJECTIVE: Burning mouth syndrome (BMS) is a chronic disorder which is affecting
      mostly postmenopausal women and is characterized by burning symptoms in the oral
      cavity on the clinically healthy oral mucosa. Also, the results of previous
      studies suggested a possible role of peripheral and/or central neurological
      disturbances in these patients. The aim of this study was to analyze patients
      with burning mouth syndrome using transcranial sonography. METHODS: By use of
      transcranial sonography of the brain parenchyma, substantia nigra, midbrain raphe
      and brain nucleus were evaluated in 20 patients with BMS (64.7+/-12.3 years) and
      20 controls with chronic pain in the lumbosacral region (61.5+/-15). Statistical
      analysis was performed by use of Student t test with significance set at p<0.05.
      RESULTS: The results of this study have shown hypoechogenicity of the substantia
      nigra and midbrain raphe as well as hyperechogenicity of the brain nucleus in BMS
      patients (p<0,05) as compared to controls. CONCLUSIONS: Altered transcranial
      sonography findings of the brain parenchyma, midbrain raphe and brain nucleus in
      patients with burning mouth syndrome might reflect central disturbances within
      this syndrome. KEY WORDS: Burning Mouth Syndrome; Transcranial Sonography;
      substantia nigra; Midbrain Raphe Nuclei; Red Nucleus.

PMID- 28740271
TI  - Fabrication of a 3D Printing Definitive Obturator Prosthesis: a Clinical Report.
AB  - INTRODUCTION: Digital technologies related to imaging and manufacturing provide
      the clinician with a wide variety of treatment options. Stereolithography (SLA)
      offers a simple and predictable way for an accurate reconstruction of congenital
      or acquired defects. CLINICAL CASE: A 65-years old cancer patient with non-
      keratinized squamous cell carcinoma of left maxillary sinus came for a prosthetic
      clinical evaluation. A bilateral maxillectomy was performed and the treatment
      plan included definite obturator prosthesis for the upper arch. CT data and 3D
      planning software were used to create a 3D printing plastic model of the defect.
      A wax pattern of the hollow bulb was fabricated and cured with heat-cured
      silicone soft liner. A final impression was obtained with the hollow bulb placed
      intraorally. The master cast was duplicated and the new cast was invested and
      reflasked. The flasks were opened, wax was boiled out and some space was created
      in the internal part of the obturator. Transparent heat cured acrylic resin was
      sandwiched with, at the inner part of the bulb, improving the retention between
      the acrylic denture base and the silicone based soft lining material. The patient
      was then placed on a 6-month recall. The five-year follow up consists of a chair
      side relining, when needed, of the definite removable prostheses. CONCLUSION:
      Maxillofacial surgery patients may develop postoperative complications such as
      trismus and pain. In these cases, the combination of digital technology and
      conventional techniques provide an accurate prosthetic restoration.

PMID- 28740272
TI  - The Modification of Rotation - Advancement Flap Made in 1950.
AB  - The early techniques of cleft lip repair involved the straight-line technique,
      the triangular flap technique or some kind of geometric line (triangular,
      quadrangular closure). A turning point in cleft lip surgery was in 1955 when
      doctor. Millard presented his method: the rotation-advancement technique or flap,
      at the First International Congress of Plastic Surgery in Stockholm. Today, the
      technique, with or without some modifications, is used by more than 85% of cleft
      surgeons around the world. We are presenting a patient with complete unilateral
      cleft lip and palate who underwent surgery sixty-five years ago. The scar on his
      lip was similar to rotation advancement line. Cheiloplasty was performed by
      Professor Sercer in 1950, five years before Millard's publication. Professor Ante
      Sercer was an internationally recognized Croatian scholar in the area of ear,
      nose and throat diseases. He also gave a significant contribution to surgical
      management of velopharyngeal insufficiency and plastic surgery of the nose and
      ear.

PMID- 28740273
TI  - Mandibular Osteonecrosis due to the Pulpal-Periodontal Syndrome: a Case Report
      and Review of the Literature.
AB  - OBJECTIVE: Ishemic bone disease has multifactorial etiologies. Cronic dental
      infections should be eliminated to prevent osteonecrosis of the jaw. CASE REPORT:
      We report an unusual case of osteonecrosis due to the pulpal-peridontal syndrome
      and subsequent pulp necrosis. A case of 38 year old woman who presented with
      exposed bone, 8 mm in diameter, in the lingual area of the right lower third
      molar. The patient was otherwise healthy and was not taking any medications. A
      detailed medical history showed no previous diseases. Patient denied any type of
      local trauma. A complete blood count showed no abnormalities. The panoramic
      radiograph revealed a deep periodontal pocket between teeth 47 and 48. The CBCT
      revealed a deep periodontal pocket between molars and bone sequestrum of the
      lingual plate. Topical treatment consisted of adhesive periodontal dressing based
      on the cellulose and bethamethasone oitnment together with orabase, without
      improvement. Therefore, peroral amoxycillin was prescribed for a week. Since
      there was no improvement, the third molar was removed as well as necrotic bone;
      the alveolar bone was remodelled and sutures were placed. After suturing, the
      whole area was covered using intraoral resorbable bandage. Microbial swab of the
      wound aspirate did not reveal polymorphonuclears or the presence of
      microorganisms. Microbial swab of the biopsy specimen of the necrotic bone
      particle and sequestrum showed a large amount of gram-positive coccae, however,
      polymorphonuclears were not found. Histopathological analysis revealed acute
      chronic inflammation. One week after the surgery, the area healed completely.
      CONCLUSION: This case highlights the fact that in some patients bone exposure
      might develop due to the pulpal-periodontal syndrome i.e. pulp necrosis.

PMID- 28740274
TI  - Direct evidence of atomic-scale structural fluctuations in catalyst
      nanoparticles.
AB  - Rational catalyst design requires an atomic scale mechanistic understanding of
      the chemical pathways involved in the catalytic process. A heterogeneous catalyst
      typically works by adsorbing reactants onto its surface, where the energies for
      specific bonds to dissociate and/or combine with other species (to form desired
      intermediate or final products) are lower. Here, using the catalytic growth of
      single-walled carbon nanotubes (SWCNTs) as a prototype reaction, we show that the
      chemical pathway may in-fact involve the entire catalyst particle, and can
      proceed via the fluctuations in the formation and decomposition of metastable
      phases in the particle interior. We record in situ and at atomic resolution, the
      dynamic phase transformations occurring in a Cobalt catalyst nanoparticle during
      SWCNT growth, using a state-of-the-art environmental transmission electron
      microscope (ETEM). The fluctuations in catalyst carbon content are quantified by
      the automated, atomic-scale structural analysis of the time-resolved ETEM images
      and correlated with the SWCNT growth rate. We find the fluctuations in the carbon
      concentration in the catalyst nanoparticle and the fluctuations in nanotube
      growth rates to be of complementary character. These findings are successfully
      explained by reactive molecular dynamics (RMD) simulations that track the spatial
      and temporal evolution of the distribution of carbon atoms within and on the
      surface of the catalyst particle. We anticipate that our approach combining real
      time, atomic-resolution image analysis and molecular dynamics simulations will
      facilitate catalyst design, improving reaction efficiencies and selectivity
      towards the growth of desired structure.

PMID- 28740275
TI  - Edible wild plant Heracleum pyrenaicum subsp. orsinii as a potential new source
      of bioactive essential oils.
AB  - Many Heracleum L. taxa (Apiaceae) are used as food and spices, and in traditional
      medicine. In this work, the chemical composition of Heracleum pyrenaicum subsp.
      orsinii (Guss.) F. Pedrotti and Pignatti root, leaf and fruit essential oils,
      their antimicrobial activity and cytotoxic effect on malignant and normal cells
      were investigated for the first time. The composition of the oils was analyzed by
      GC and GC-MS. Monoterpenes prevailed in the root oil, with beta-pinene (38.6%)
      being dominant, while in the leaf oil, sesquiterpenes, mostly (E)-nerolidol
      (20.5%) and (E)-caryophyllene (17.0%), were the most abundant constituents. The
      fruit oil contained the majority of aliphatic esters, mainly octyl acetate
      (36.8%) and octyl hexanoate (22.1%). The antimicrobial activity was determined by
      microdilution method against eight bacteria and eight fungi (standard strains,
      clinical or food isolates). The best antibacterial activity, better than the
      activity of ampicillin, was shown by the root oil against Salmonella typhimurium,
      Escherichia coli and Pseudomonas aeruginosa. The strongest antifungal activity,
      stronger than the activity of ketoconazole, was exhibited by the leaf and root
      oils against Trichoderma viride, and by the root oil against Aspergillus
      ochraceus. The cytotoxic effect of the oils, determined by MTT test, was
      prominent against malignant HeLa, LS174 and A549 cells (IC50 = 6.49-14.56
      MUg/mL). On the other hand, the oils did not show toxicity against normal MRC-5
      cells at tested concentrations (IC50 > 200.00 MUg/mL). It can be concluded that
      investigated H. pyrenaicum subsp. orsinii oils represent potential new raw
      materials for food and pharmaceutical industry.

PMID- 28740276
TI  - Effects of microbial transglutaminase on physicochemical properties,
      electrophoretic patterns and sensory attributes of veggie burger.
AB  - The main objective of this study was to investigate the effects of microbial
      transglutaminase (MTGase 0-0.75%)/sodium-caseinate (SC 0-2%) as crosslinker
      agents on proximate analysis, binding properties (expressible moisture and
      shrinkage), texture analysis, electrophoretic patterns, instrumental color, and
      sensory properties of veggie burgers. Addition of SC and MTGase positively
      affected shrinkage and expressible moisture. It also increased hardness,
      springiness, chewiness, and cutting-force of burgers. Presence of SC had no
      effects on cohesiveness of burgers. Total protein and ash of samples were
      increased by treatment with SC. The lightness (L*) of samples was significantly
      decreased by 0.75% MTGase. No significant influence of SC on samples color
      parameters was observed. The results indicated that distinct protein bands were
      not formed on the SDS-PAGE of burger samples and resulted in a smearing pattern
      on the gel. When soy-protein was incubated with MTGase, a progressive decrease in
      the intensity of the bands corresponding to the subunits 7S and 11S globulins was
      observed concomitant with disappearance of A3 and B3 bands. Electrophoresis
      pattern of gluten was slightly changed after MTGase treatment. There were
      significant differences in color, taste, appearance, mouth feel, and overall
      acceptability between treated and control samples. Results suggest that
      production of veggie burgers using MTGase alone or in combination with SC brings
      about covalent cross-linking between homologous and heterologous proteins to form
      high-molecular weight polymers, thereby improving the mechanical properties of
      veggie burgers and profoundly increases the acceptability of the end product.

PMID- 28740277
TI  - The influence of ultrasonic treatment on the growth of the strains of Salmonella
      enterica subs. typhimurium.
AB  - This study proposes the destruction of pathogenic bacteria with the use of
      ultrasound waves because the more commonly used thermal processing methods often
      result in lowering the nutritional value of food. The study presents the impact
      of ultrasound of 20, 40 and 100 kHz frequencies and the power of 10.5 W/cm2 on
      the growth of the strain of Salmonella enterica subs. typhimurium. The tests were
      carried out both in chilled and non-chilled treatment mediums, with an average
      bacterial population >105 and >108 CFU/cm3. The total inactivation of Salmonella
      spp. was observed in the tests in the low-population non-chilled treatment medium
      after sonication at 20 and 40 kHz for 30 min, and in high bacterial population at
      20 kHz for 30 min. A reduction in the average number of bacteria was reported in
      the low-population non-chilled medium after 15 min of sonication at 20, 40 and
      100 kHz; after 15 min of sonication at 20 and 100 kHz of the material of high
      bacterial population; and in the low-population chilled treatment mediums after
      15 and 30 min at 20 kHz. The samples with inactivated bacteria and those with
      reduced bacterial counts maintained the same levels when stored at 4  degrees C
      for 24 and 48 h. Bacteria inactivation obtained after sonication lasted for up to
      48 h in storage at 21  degrees C. For the samples with reduced bacterial counts
      stored at 21  degrees C, a rise in the average number of bacteria was recorded.

PMID- 28740278
TI  - Effects of deep-fat frying process on the oil quality during French fries
      preparation.
AB  - The performance of the sunflower oil in deep-fat frying was assessed by
      evaluating the efficacy of linoleic acid level and composition of tocopherol
      isomeric on its frying stability. The oil was used as a frying media to fry
      potato strips for 6 h daily for 7 days. Standard procedures for the measurement
      of used frying oil degradation such as fatty acid composition, acid value,
      anisidine value, conjugated diene value, total polar compounds and tocopherol
      concentration were used. At analogous composition of tocopherol isomers, the high
      oleic sunflower oil with smaller value of linoleic acid content indicated higher
      frying stability than the oil with higher linoleic acid level. This, indicating
      that the high oleic sunflower oil frying efficiency was depended mainly with the
      oil linoleic acid content and the composition of tocopherol isomers showed no
      significant effect. Also, the alpha-tocopherol degradation was lower compared to
      the corresponding degradation of gamma-tocopherol.

PMID- 28740279
TI  - Effect of harvest time on physico-chemical properties and bioactive compounds of
      pulp and seeds of grape varieties.
AB  - In this study, physicochemical properties and bioactive compounds of three grape
      varieties (Cardinal, Muskule and Razaki) harvested at the three different harvest
      times (on time, one and two weeks earlier) were investigated. The highest
      antioxidant activity, total phenolic and flavonoid contents were observed in
      Razaki pulp and these were 82.854%, 127.422 mg/100 g, 3.873 mg/g, respectively.
      The contents of bioactive compounds in grape seeds were found higher than those
      in pulps. Similarly, seed of Razaki had higher antioxidant activity (91.267%) and
      total phenolic content (477.500 mg/100 g) when compared to results of other
      varieties. The key phenolic compounds of all grape variety and seeds were gallic
      acid, 3,4-dihydroxybenzoic acid, (+)-catechin ve 1,2-dihydroxybenzene. The oil
      content of grape seeds ranged from 8.50% (Razaki harvested one week ago) to
      19.024% (Muskule harvested one week ago). The main fatty acids of grapeseed oils
      were linoleic, oleic and palmitic acids. In addition, the oil of Razaki seeds was
      rich in tocopherols when compared to the other varieties.

PMID- 28740280
TI  - Process optimization of spray drying of beetroot Juice.
AB  - The aim of this study was to optimize the spray drying process for beetroot
      juice. Influence of feed flow rate (8, 10 and 11 mL/min), processing temperature
      (140, 150 and 160  degrees C) and maltodextrin concentration (20, 25, and 30%) on
      packed bulk density, moisture content and betalain content of beetroot powder
      were assessed using response surface methodology. The following optimum process
      parameters were determined; feed flow rate feed flow rate of 10 mL/min,
      processing temperature of 149  degrees C and maltodextrin concentration of 20%.
      The predicted values for packed bulk density, moisture content and betalain
      content were 0.62 g/mL, 6.12 and 33.84 mg/100 g of dry matter, respectively.
      Within the optimum parameters, the experimental values for packed bulk density,
      moisture content and betalain content were 0.62 +/- 0.1 g/mL, 6.10 +/- 0.1 and
      33.14 +/- 0.1 mg/100 gm of dry matter. The similarity of the experimental results
      to the predicted values verified the models.

PMID- 28740281
TI  - Evaluating and correlating the mechanical, nutritional, and structural properties
      of carrots after multiple freezing/thawing processing.
AB  - This work evaluated and correlated the mechanical and nutritional properties of
      carrots after five freezing/thawing cycles (FTC). Results showed that after one
      FTC, the mechanical parameters (hardness, chewiness, springiness, cohesiveness,
      resilience, and storage modulus) and the glucose and fructose content sharply
      decreased and the tangent (Tandelta) dramatically increased in samples. The
      contents of lycopene and lutein reached the maximum level after two FTC. And
      there were no significant changes in the content of alpha- and beta-carotene
      (around 90 and 50 mg 100 g-1 dry matter, respectively) among all samples.
      Correlation analysis showed that the mechanical parameters were positively
      correlated with soluble sugars (fructose, glucose, and sucrose) and negatively
      with lycopene and lutein Tandelta were negatively related with soluble sugar.
      These results suggested that the first freezing/thawing condition could be the
      key factor for obtaining the products with acceptable quality. The changes in
      macroscopic mechanics could be used to predict the variations of potential
      nutritional components in tissues during FTC processing. The deteriorated
      structural changes (i.g. cell wall dissociation and turgidity loss) could be
      responsible for these results.

PMID- 28740282
TI  - Effects of marine collagen peptides on glucose metabolism and insulin resistance
      in type 2 diabetic rats.
AB  - The present study was conducted to investigate the effects of marine collagen
      peptides (MCPs) on glucose metabolism and insulin resistance using a rat model of
      type 2 diabetes mellitus (T2DM). Forty T2DM obese Wistar rats were randomly
      assigned to receive varying doses of MCPs or a vehicle control for 4 weeks. Blood
      glucose and insulin levels, as well as oxidative stress and inflammation were
      measured. The expression of glucose transporter type 4 (GLUT4) in skeletal
      muscles and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in
      livers of T2DM rats was also measured. It was found that in the group of 9.0
      g/kg/day MCPs significantly improved glucose, insulin, and homeostatic model
      assessment-insulin resistance, and increased the insulin sensitivity index (ISI).
      In addition, the groups of 4.5 and 2.25 g/kg/day MCPs significantly improved
      liver steatosis. It was also found that MCPs decreased expression of oxidative
      stress biomarkers and inflammatory cytokines and adipocytokines in T2DM rats. In
      conclusion, medium and high doses of MCPs (>=4.5 g/kg/day) improved glucose
      metabolism and insulin sensitivity in T2DM rats. These beneficial effects of MCPs
      may be mediated by decreasing oxidative stress and inflammation and by up
      regulating GLUT4, and PPAR-alpha activity.

PMID- 28740283
TI  - Use of response surface methodology (RSM) to optimize pea starch-chitosan novel
      edible film formulation.
AB  - The aim of this study was to develop an optimal formulation for preparation of
      edible films from chitosan, pea starch and glycerol using response surface
      methodology. Three independent variables were assigned comprising chitosan (1
      2%), pea starch (0.5-1.5%) and glycerol (0.5-1%) to design an empirical model
      best fit in physical, mechanical and barrier attributes. Impacts of independent
      variables on thickness, moisture content, solubility, tensile strength, elastic
      modulus, elongation at break and water vapor permeability of films were
      evaluated. All the parameters were found to have significant effects on physical
      and mechanical properties of film. The optimal formulation for preparation of
      edible film from chitosan, pea starch and glycerol was 1% chitosan, 1.5% pea
      starch and 0.5% glycerol. Edible films with good physical and mechanical
      properties can be prepared with this formulation and thus this formulation can be
      further applied for testing on coating for fruit and vegetables.

PMID- 28740284
TI  - The effect of mechanical processing on avenanthramide and phenol levels in two
      organically grown Italian oat cultivars.
AB  - Avenanthramides (AVNs), free and bound phenols and their antioxidant capacities
      (ORAC) were evaluated in two Avena sativa L. cultivars, Donata and Flavia. The
      cultivars (cvs.) were grown in loamy and medium texture soils and assessed after
      industrial dehulling and milling. Total dietary fiber, beta-glucan, starch and
      proteins were also evaluated. Cv. Donata showed 2.8 fold higher AVN storage as
      compared to cv. Flavia, which was linked with genotype. The accumulation of AVN
      content was also influenced by the texture of the soil. Dehulling resulted in a
      75 and 37% AVN decrease in cv. Donata and Flavia, respectively. The dehulled
      grains of cv. Donata showed 40% reduction in free phenolic content, whereas the
      dehulled grains of both cvs. showed 67% reduction in bound phenols. Milling
      affected the bound phenolics and their antioxidant capacity. Cv. Flavia showed
      1.3 fold higher beta-glucan than that of cv. Donata. Total dietary fiber was
      reduced by 50 and 12% after dehulling and milling, respectively, while marginal
      changes in proteins were observed after milling. The results suggest that the
      choice of genotype and the kind of dehulling processes that are employed are
      essential considerations in the production of oat-based products with high AVN
      content and extra health benefits.

PMID- 28740285
TI  - Variation of active constituents and antioxidant activity in Scabiosa
      tschiliensis Grunning from different stages.
AB  - It has been claimed that inflorescences of Scabiosa tschiliensis Grunning (ST)
      may prevent liver diseases because of its higher chlorogenic acid. There was
      scant information on the phytochemical profiles and antioxidant activities of the
      whole plant from different growing stages. The changes of active-compounds and
      antioxidant activities of ST from three growing stages were studied. Total
      phenolic and flavonoid contents were analyzed and ranged from 0.00 to 140.03 mg
      GAE/g and 9.10 to 460.01 mg RE/g, respectively. The pre-flowering stage ethyl
      acetate (PFSEA) fraction of ST appeared to contain the highest content of
      chlorogenic acid, and demonstrated the highest DPPH radical-scavenging activity
      with the IC50 value of 8.47 +/- 0.23 ug/mL which was nearly equal to the IC50
      value of vitamin C (7.60 +/- 0.61 ug/mL). Principal component analysis suggested
      that the PFSEA fraction of ST might be a desirable antioxidant natural resource
      due to the highest potential antioxidant properties.

PMID- 28740286
TI  - Physicochemical, melissopalynological and antioxidant properties of artisanal
      honeys from Lebanon.
AB  - Sixteen honeydew and 15 floral honeys from Lebanon were analyzed for pollen
      spectra and physicochemical parameters. A total of 37 families and 67 taxa were
      recorded with the honeybees producing honeydew honey exhibiting a more diverse
      foraging behavior than those making floral honeys. The honeydew and floral honeys
      exhibited differences in moisture content, pH, electrical conductivity, color,
      protein and Maillard reaction products. The honeydew honeys contained more total
      phenols, had higher antioxidant contents, and displayed higher antioxidant
      capacities than the floral samples in the Trolox equivalent antioxidant capacity,
      oxygen radical absorbance capacity, inhibition of superoxide dismutase activity
      and protection of red blood cells against hemolysis assays. The honey samples
      exhibited higher antioxidant capacities, in the aforementioned assays, than their
      corresponding methanol-extractable phenol fractions although the differences did
      not reach statistical significance in the floral samples. The relative
      antioxidant capacity indices which integrate measures of antioxidant capacity
      from the different assays of the honey samples and their corresponding extracts
      exhibited similar patterns (r = 0.9774, 0.9937) thereby indicating that the
      antioxidative behavior of the entire honeys is mirrored by their methanol
      extractable phenolic fractions.

PMID- 28740287
TI  - Evaluating the antimicrobial potential of green cardamom essential oil focusing
      on quorum sensing inhibition of Chromobacterium violaceum.
AB  - Spices are well known for their taste and flavor imparting properties. Green
      cardamom (Elletaria cardamomum), a herb spice belongs to family Zingiberaceae. In
      current study, GC-MS analysis of green cardamom essential oil (CEO) resulted in
      identification of twenty-six compounds with alpha-terpinyl acetate (38.4%), 1,8
      cineole (28.71%), linalool acetate (8.42%), sabinene (5.21%), and linalool
      (3.97%) as major bioactive components. Present study also described the
      antimicrobial properties like zone of inhibition, minimum inhibitory
      concentration against microbial strains with special emphasis on quorum sensing
      inhibition. Disk diffusion assay showed that C. albicans and S. mutans were the
      most sensitive microorganisms followed by S. aureus, L. monocytogenes, B. cereus
      and S. typhimurium sensor strains, respectively. Whilst P. aeruginosa was found
      most resistant strain as CEO did not inhibited its growth. The minimum inhibitory
      concentration (MIC) values of CEO against tested strains were 10 +/- 0.00 mg/mL
      against S. typhimurium, S. aureus and 5 +/- 0.00 mg/mL against S. mutans, C.
      albicans strains, respectively. Regarding quorum sensing inhibition the tested
      concentrations 0.625 and 0.313 mg/mL of CEO inhibited violacein production with
      very little effect on growth of C. violaceum. Conclusively, study proved that
      quorum sensing inhibition values of CEO were much lower compared to MIC revealed
      values. Hence, cardamom bioactive constituents can effectively be used to develop
      novel antimicrobial drugs against conventional antibiotics.

PMID- 28740288
TI  - Polyphenol patterns to trace sweet (Prunus avium) and tart (Prunus cerasus)
      varieties in cherry jam.
AB  - The aim of this work was to assess whether the characteristic polyphenol traits
      of cherry biotypes persisted in thermally processed cherry products, such as jam.
      Thus, the RP-HPLC-diode array detector profiles of both colorless polyphenols and
      anthocyanins from three cherry varieties (two sweet and one tart cherry) were
      compared with those of low-sugar jam sourced from the same cultivars. Individual
      components were characterized by mass spectrometry. The total phenolic and total
      anthocyanin content as well as the radical scavenging potential (residual 75-91,
      88-91 and 73-75%, respectively) were only slightly reduced by deep thermal
      treatments. Apart from the interconversion among the isomers of chlorogenic acid,
      the profile of both colorless polyphenols and anthocyanins substantially survived
      the jam manufacturing under conventional temperature-time regimen (80  degrees C,
      1 h). The species- and cultivar-specific polyphenol molecular asset, especially
      the anthocyanin pattern, has potential to be monitored for traceability purpose,
      aimed to the varietal assessment of cherry biotypes used for producing jam.

PMID- 28740289
TI  - Antioxidant efficiency of polyphenols from coffee and coffee substitutes
      electrochemical versus spectrophotometric approach.
AB  - Antioxidant (AO) capacity of instant, espresso, filter and Turkish/Greek coffee
      brews, coffee substitutes (roasted chicory root, barley, pea, chickpea, carob and
      dried fig) and individual compounds (phenolic acids, flavonoids, methylxanthines,
      N-methyl pyridinium and HMW melanoidins) was assessed using DC polarographic
      assay based on decrease of anodic current originating from hydroxo-perhydroxo
      mercury complex formed in alkaline solutions of H2O2 at potential of mercury
      dissolution, as well as three spectrophotometric assays (DPPH, ABTS and FRAP). A
      large difference between applied assays ability to recognize various types of
      individual AOs was noticed. Only according to DC polarographic assay significant
      AO activity was ascribed to methylxanthines and N-methyl pyridinum. The total
      content of phenolics (TPC) present in complex samples was determined by FC assay.
      The highest TPC was ascribed to instant coffees and coffee substitutes while the
      lowest to decaffeinated filter coffee. Complex samples were grouped based on
      principal components analysis, phenolics AO coefficient, calculated as the ratio
      between AO capacity and TPC, and relative AO capacity index (RACI), calculated by
      assigning equal weight to all applied assays including FC. The highest values of
      RACI were ascribed to instant coffee brews, followed by substitutes while the
      lowest to the decaffeinated espresso coffee.

PMID- 28740290
TI  - The influence of pulsed light exposure mode on quality and bioactive compounds of
      fresh-cut mangoes.
AB  - This study investigated the effect of pulsed light (PL) on the respiratory rate,
      quality (firmness, color and soluble solid content), bioactive compounds
      (ascorbate and carotenoid) and total antioxidant activity of fresh-cut "Tommy
      Atkins" mangoes. Fresh-cut mangoes were subjected to PL treatments: control (0P),
      1 pulse (1P; 0.7 J cm-2), 4 successive pulses (4P; 2.80 J cm-2) and 1 pulse per
      day for 4 days (1P4D; 2.80 J cm-2) before storage for 7 days at 6  degrees C. The
      1P and the 4P treatments reduced fresh mass loss during storage, while 4P-treated
      samples also showed a slower decline of yellow color, as shown by parameter b and
      overall better visual appearance. After 7 days of storage, total ascorbate
      content was 40% higher in the 1P4D treatment than in control, whereas total
      carotenoid content (0.894 mg g-1 FM) and total antioxidant activity (144 MUmol
      trolox 100 g-1 FM) were the highest in the 4P-treated samples. Results suggest
      that PL mode of application is more important than the fluence or final dose
      received by fresh-cut mangoes; moreover, 4P is an effective method to preserve,
      or even improve quality of fresh-cut mangoes.

PMID- 28740291
TI  - Effect of high-pressure processing on quality and stability of green mango
      blended mayonnaise.
AB  - The present work was aimed to study and optimize the high pressure treated green
      mango blended mayonnaise in terms of oxidative and emulsion stability, as a
      function of technical parameters; pressure intensity, dwell period and level of
      green mango pulp. Mayonnaise samples were treated at different combinations of
      pressure (400-600 MPa), holding time (5-10 min) and level of green mango pulp (10
      30%) following Box-Behnken design. Mayonnaise quality was evaluated in terms of
      oxidative stability and emulsion stability using response surface methodology to
      optimize the best possible combination among all. Analysis of variance showed
      that the second-order polynomial model fitted well with the experimental results.
      Pressure and time were the most important factors determining the oxidative
      stability (free fatty acids, peroxide value and anisidine value) whereas; the
      emulsion stability (creaming and thermal creaming) was most significantly
      affected by the level of green mango pulp. The optimized conditions for preparing
      green mango blended mayonnaise with high oxidative and emulsion stability were:
      435 MPa pressure, 5 min of holding time with the addition of green mango pulp at
      the rate of 28%. The product prepared at optimum conditions showed good
      correlations between predicted and actual values.

PMID- 28740292
TI  - Optimization of low-fat set-type yoghurt: effect of altered whey protein to
      casein ratio, fat content and microbial transglutaminase on rheological and
      sensorial properties.
AB  - In the present study the amount of whey protein to casein ratio (W/C ratio) (0.22
      0.7), fat content (FC) (0.5-1.5%) and microbial transglutaminase (mTGase) (0.0
      1.0 U/g substrate protein) in the formulation of low fat set type yoghurt,
      prepared from reconstituted milk, were optimized by response surface method to
      achieve the best rheological properties and sensory characteristics. The selected
      parameters consisted of higher consistency coefficient, consistency, texture and
      mouth feeling and lower syneresis and pH. The optimum condition was found to be
      0.97, 0.46 and 0.5% of the enzyme concentration, W/C ratio and FC respectively.
      Results showed that thermal denaturation increased up to 33% with increasing W/C
      ratio significantly. All samples showed non-Newtonian shear thinning behavior.
      Increasing in W/C ratio from 0.22 to 0.7 raised the consistency coefficient,
      yield stress and textural parameters such as hardness and consistency of yoghurt.
      Enzyme addition (together with starter culture addition) increased yoghurt
      viscosity and yield stress. In sensory evaluation W/C ratio affected the texture
      and mouth feeling of yoghurt samples and the influences of FC and mTGase were not
      significant. Yoghurt syneresis was highly affected by FC, W/C ratio and mTGase.

PMID- 28740293
TI  - Ultrasound-assisted extraction process of phenolic antioxidants from Olive
      leaves: a nutraceutical study using RSM and LC-ESI-DAD-MS.
AB  - In recent years, there has been an ever growing interest in finding new natural
      sources of food antioxidants. As a main fruit crop, olive is also valued due to
      its phenolic-containing leaves. Mathematically based optimization methods are
      used as powerful tools to extract different antioxidant compounds. The present
      study is aimed to provide an efficient extraction method for total phenol content
      (TPC), total flavonoid content (TFC) and antioxidant ability (DPPH scavenging
      assay and FRAP). The effects of ultrasonic temperature (35-65  degrees C),
      ultrasonic time (5-15 min), and ethanol to water ratio (Et: W) (25-75%) were
      evaluated. Second-order polynomial models were used through a rotatable Box
      Behnken design (BBD) consisting of 15 experimental runs with three replicates at
      the center point. Interactional effects of the studied factors were significant
      in most cases for all responses. The highest extraction efficiency was found to
      be fifty-one percent of ethanol (65  degrees C, 15 min) to water ratio. Under
      optimal conditions, values for TPC, TFC, DPPHsc and FRAP assay were 183.4 (mg
      GAE. g-1 DW), 696.77 (mg Quercetin. g-1 DW), 78.98 (DPPHsc %) and 1942 umol
      Fe+2/g DW, respectively. R2 values (R2 > 0.92) showed that RSM models could
      efficiently predict the yield of all responses. In the LC-ESI-MS-DAD profiling of
      the optimized extract, 27 compounds were identified with oleuropein as the main
      compound. In the present study, olive leaf is introduced as a promising source of
      natural antioxidant and can be used in food industries following further studies.

PMID- 28740294
TI  - Chemical composition of potato tubers: the effect of cultivars and growth
      conditions.
AB  - The aim of the study involved evaluating the chemical composition of tubers of
      five potato cultivars that were grown under the same cultural practices in soils
      with low, medium, and high availability of phosphorus. The experimental designs
      corresponded to a randomized block with four replicates. Tuber samples were
      analyzed in terms of moisture, ash, protein, lipid, total sugar, fiber, starch,
      and phosphorus contents. The results suggested that increased availability of
      phosphorus in soil allowed the production of tubers with higher dry matter
      content, lower total sugar content, and a higher percentage of starch and
      protein. Hence, the aforementioned parameters constitute important factors
      corresponding to the nutritional and industrial quality of potatoes. Increased
      phosphorus availability in soil can promote significant changes in the
      composition of potato tubers, and thereby in potential uses of tubers.

PMID- 28740295
TI  - Inhibition of foodborne bacteria by antibacterial coatings printed onto food
      packaging films.
AB  - Films containing antibacterial compounds could be used for packaging perishable
      foods such as fresh fish and meat for sea freighting over long distances.
      However, existing commercialised options (films with nanosilver zeolites or
      wasabi extract) are only permitted for food contact in certain regions and films
      containing alternative antibacterial ingredients are required e.g. for exports to
      Europe. Certain non-volatile phenolic plant extracts have shown promising
      antibacterial activity against a wide range of foodborne bacteria in in vitro
      assays and when integrated in coatings for perishable foods such as fish and
      meat. Extracts rich in gallotannins tend to show stronger antibacterial effects
      than other phenols such as flavonoids. Such extracts could be coated onto
      commercial barrier films by means of flexographic printing-a more industrially
      feasible option than rod coating or solvent casting typically used in
      antibacterial coating research. The goal of the present work was to investigate
      the antibacterial effect of printed latex coatings containing extracts rich in
      gallotannins and other types of phenolic compounds against 16 common spoilage and
      pathogenic bacteria of fish and meat. The largest zones of inhibition in disk
      diffusion assays were obtained with plastic films with coatings containing tannic
      acid alone, followed by tannic acid with phenolic-rich extracts of feijoa skin or
      mango seed. Significant inhibition was seen for all bacteria. This study shows
      that coatings with gallotannins as the main active ingredient can be printed onto
      commercial barrier films to control the bacteria that limit the shelf-life of
      fresh fish and meat.

PMID- 28740296
TI  - Lithium biofortification of medicinal mushrooms Agrocybe cylindracea and Hericium
      erinaceus.
AB  - Although an increase in dietary lithium (Li) has been suggested as a possible
      method for mood stabilization and for decreasing violence and suicidal rates, no
      Li-enriched food has entered the market. Here we continue to explore the
      feasibility of mushrooms in this respect and have investigated the growth,
      accumulation and mineral content (Ca, K, Mg and Na) of Agrocybe cylidracea and
      Hericium erinaceus cultivated on substrates supplemented with 0.25-1.0 mM of Li
      as acetate or chloride. As demonstrated, supplementation with LiCl yielded more
      satisfactory results, did not alter mushroom biomass, appearance, shape or size
      regardless of Li concentration. It also had no significant effect on mineral
      composition and resulted in a concentration-dependent uptake of Li and its
      accumulation in fruiting bodies. More promising results were found for H.
      erinaceus. As calculated, consumption of 100 g dw of its fruiting bodies obtained
      from cultivation with 1.0 mM of Li (as acetate or chloride) would constitute 69%
      of the provisional recommended dietary daily intake of Li set at 1.0 mg. The
      study highlights that H. erinaceus could be selected for further studies on Li
      enriched food that concern the bioavailability of Li from mushrooms, their safety
      and activity in animal experimental models and eventually, human studies.

PMID- 28740297
TI  - Adulteration identification in raw milk using Fourier transform infrared
      spectroscopy.
AB  - Adulteration of milk is a common practice that concerns regulatory agencies,
      industry, and the population. Despite the growing need for checking adulteration,
      the current methods employed generally have low performance and are highly
      dependent on manual labor. This study aims to calibrate and validate a compact
      equipment (MilkoScan FT1) that adopts a Fourier transform infrared spectroscopy
      methodology to monitor adulteration in raw milk. Almost 2500 milk samples were
      used for reference spectrum construction and 1650 samples were used to validate
      the identification of the following five most commonly used adulterants (at three
      different concentrations each): (1) cornstarch, (2) sodium bicarbonate, (3)
      sodium citrate, (4) formaldehyde, and (5) saccharose, plus the additions of two
      levels of water or whey. To define the calibration with the best performance in
      milk adulteration identification, 12 calibrations involving 8, 10, 12, 14, 16, or
      18 factors, with one or two outlier eliminations, were developed. The results of
      sensitivity and specificity analyses, as well as Kruskal-Wallis and Dunn multiple
      comparison tests, revealed that the calibration that best identified the
      adulterants was the one involving 14 factors, with a single elimination of
      outliers, exhibiting for all adulterants simultaneously, 84% sensitivity and 100%
      specificity. The calibration showed excellent sensitivity to cornstarch (>98%),
      sodium bicarbonate (100%), sodium citrate (99%), and formaldehyde (>84%),
      indicating that this calibration has good capacity for adulteration detection.
      Thus, this methodology is a viable option for the dairy industry to identify
      adulteration of raw milk.

PMID- 28740298
TI  - Thermal, pasting and morphological properties of starch granules of wheat
      (Triticum aestivum L.) varieties.
AB  - Large (A) and small (B) granules of wheat starch were separated and their
      morphological, thermal, structural and pasting properties were investigated. The
      pasting properties of starches from two wheat varieties showed significant
      differences. For wheat variety C-306, the unfractionated starch showed higher
      peak, trough, breakdown, final, and setback viscosities than the starch isolated
      from wheat variety WH-147. On the contrary, unfractionated starch of variety WH
      147 has higher pasting temperature than the starch of the variety C-306.
      Differential scanning calorimetry results showed that unfractionated starch
      exhibited the higher gelatinization enthalpy, peak and conclusion temperatures
      than the isolated A- and B-starch granules from both the varieties. Scanning
      electron microscopy results revealed that large A-granules appeared to be smooth
      and displayed disk or lenticular shape having diameter 13-35 MUm, while B
      granules showed a spherical shape with diameter of 2-6 MUm. The variations in
      structures and content would result in starch granules with different chemical
      and physical properties.

PMID- 28740299
TI  - Attenuation of diabetic retinopathy in rats by ellagic acid through inhibition of
      AGE formation.
AB  - Diabetic retinopathy (DR) is a major concern for blindness all over the world.
      Diabetic retinopathy is associated with thickening of basement membrane, retinal
      thinning, retinal detachment, and pericyte death. Advanced glycation end products
      (AGEs) mediate the progression of DR by stimulating the expression of RAGE and
      VEGF which subsequently damages the blood-retinal barrier. Employing a set of in
      vitro protein glycation systems, earlier we demonstrated antiglycating potential
      of ellagic acid (EA). In this study, we evaluated the efficacy of EA to prevent
      in vivo accumulation of AGE and to ameliorate retinal changes in diabetic rats.
      Streptozotocin-induced diabetic rats were fed either with 0.2 or 2% EA in the
      diet for 12 weeks. Effect of EA on retinal function was assessed with
      electroretinogram (ERG). At the end of the experiment, rats were scarified and
      retina was collected. Histology was carried out with H&E staining and
      immunohistochemistry. Formation of AGE product (CML) and activation of RAGE was
      analyzed by immunoblotting and immunohistochemistry. Expression of GFAP, VEGF,
      Bax and HIF-1alpha was assessed by qRT-PCR and immunoblotting. Dietary
      supplementation of EA to diabetic rats resulted in: (1) inhibition of
      accumulation of CML and activation of RAGE in retina, (2) attenuation of
      expression of GFAP, VEGF, and HIF-1alpha in retina, (3) attenuation of cell death
      by reducing proapoptic mediator Bax and (4) amelioration of retinal thickness and
      function. In conclusion, EA attenuated the retinal abnormalities including
      angiogenesis, hypoxia and cell death by inhibiting AGE-RAGE mediated cellular
      events.

PMID- 28740300
TI  - Feasibility of UV-VIS-Fluorescence spectroscopy combined with pattern recognition
      techniques to authenticate a new category of plant food supplements.
AB  - Bud extracts, named also "gemmoderivatives", are a new category of natural
      products, obtained macerating meristematic fresh tissues of trees and plants. In
      the European Community these botanical remedies are classified as plant food
      supplements. Nowadays these products are still poorly studied, even if they are
      widely used and commercialized. Several analytical tools for the quality control
      of these very expensive supplements are urgently needed in order to avoid
      mislabelling and frauds. In fact, besides the usual quality controls common to
      the other botanical dietary supplements, these extracts should be checked in
      order to quickly detect if the cheaper adult parts of the plants are deceptively
      used in place of the corresponding buds whose harvest-period and production are
      extremely limited. This study aims to provide a screening analytical method based
      on UV-VIS-Fluorescence spectroscopy coupled to multivariate analysis for a rapid,
      inexpensive and non-destructive quality control of these products.

PMID- 28740301
TI  - Effect of modified atmosphere packaging and temperature abuse on flavor related
      volatile compounds of rocket leaves (Diplotaxis tenuifolia L.).
AB  - The effect of storage conditions on flavor-related volatile composition of wild
      rocket (Diplotaxis tenuifolia) was investigated on Modified Atmosphere packed
      (MAP) leaves stored under isothermal and non-isothermal conditions. In a first
      experiment the effect of MAP was compared to the storage in air at 5  degrees C;
      a second experiment aimed to study the effect of non isothermal conditions, with
      two temperature abuses (at 13  degrees C for 24 h) during a 5  degrees C. Twenty
      four volatiles were detected, including C6, C5, isothiocyanate, lipid-derived and
      sulfur compounds. In the first experiment, MAP-stored rocket showed a slower loss
      of typical flavour volatiles (thiocyanates and isothiocyanates) and a slower
      production of off-flavors until 6 days of storage, compared to leaves stored in
      air. After this time, dimethyl sulfide and acetaldehyde dramatically increased in
      MAP-stored rocket samples. In the second experiment, samples stored under non
      isothermal conditions showed lower O2 and higher CO2 concentrations than samples
      stored under isothermal conditions. Rocket leaves stored under non-isothermal
      conditions showed an increased production of volatiles responsible of off-flavors
      (acetaldehyde and dimethyl sulfide) following temperature abuse comparing to
      storage in isothermal condition. Thus, dimethyl sulfide and acetaldehyde could be
      effective markers for tracking the effect of temperature fluctuations on rocket
      during storage.

PMID- 28740302
TI  - Effect of inulin on physico-chemical, sensory, fatty acid profile and
      microstructure of processed cheese spread.
AB  - To develop a functional processed cheese spread (PCS) different levels of inulin
      (0, 4, 6 and 8%) addition into PCS was studied with its physico-chemical, sensory
      and fatty acid profile and micro-structural quality. As the level of inulin
      addition increased moisture, aw and titratable acidity, decreased. At the highest
      level of inulin addition (8%) sensory panelists reported a significant decrease
      in total sensory score. PCS with 6% insulin was found to have optimum from
      quantity. The addition of inulin in cheese spread decreased both total saturated
      fatty acid and unsaturated fatty acid and in unsaturated fatty acid, mono
      unsaturated fatty acid decreased; however, polyunsaturated fatty acids increased
      as compared to the control. Scanning Electron Micrograph of PCS containing
      insulin showed uniform distribution of insulin with diameter ranged 4-10 um in
      the protein matrix.

PMID- 28740303
TI  - Kinetic modeling to study the quality of tambaqui (Colossoma macropomum) sous
      vide during storage at different temperatures.
AB  - This study aimed to assess the changes in quality of tambaqui sous vide during
      refrigerated storage using degradation kinetics. Tambaqui sous vide was prepared
      and stored at three temperatures (1, 4, 10  degrees C). The microorganism counts
      and the physicochemical analyses were analyzed every three days. The results
      obtained were fitted to the Labuza models and by Arrhenius equation. The results
      of the microbiological and physicochemical analyses obtained better fits to the
      zero-order model. The Arrhenius equation better fit to the velocity constants of
      the zero-order model, which showed that the changes in the values of attributes
      are related to temperature. Higher Ea values were found for the microorganism
      counts than for the physicochemical parameters, which proves the greater
      dependency of microorganisms on variations in temperature. The assessment of
      changes in quality based on temperature allows the storage conditions to be
      optimized.

PMID- 28740304
TI  - Improving oxidative stability of virgin olive oil by addition of microalga
      Chlorella vulgaris biomass.
AB  - Antioxidant activity of Chlorella (Chlorella vulgaris) was evaluated in virgin
      olive oil (VOO) at different concentrations of 0.5, 1.0, and 1.5% (w/w) under
      accelerated storage conditions. Antioxidant activity of Chlorella was compared
      with those of BHT and beta-carotene. Chlorella samples significantly retarded the
      formation of primary, secondary, and total oxidation products in comparison with
      those of the control. The stability increased as concentrations of Chlorella
      increased. Samples containing 0.5, 1.0, and 1.5% Chlorella significantly improved
      VOO stability by 19.99, 28.83, and 33.14%, respectively. Observed effects can be
      related to the release in the assortment of bioactive compounds from Chlorella
      algae to the VOO. Among the different antioxidants evaluatedy, BHT exhibited the
      highest antioxidant activity. On the contrary, beta-carotene had no preventive
      effect against the oxidation of VOO. It also proved incapable of limiting the
      progress of VOO oxidation and played role as pro-oxidant. In conclusion,
      Chlorella enhanced VOO oxidative stability. Thus it can be considered as a
      promising source of natural antioxidants.

PMID- 28740305
TI  - Swelling and infusion of tea in tea bags.
AB  - The present study deals with swelling and infusion kinetics of tea granules in
      tea bags. The swelling and infusion kinetics of tea bags differing in tea loading
      and tea bag shapes were compared with loose tea. Increment in temperature and
      dipping frequency of tea bag in hot water increased the infusion kinetics of tea
      bags. Reduction in particle size enhanced the swelling and infusion kinetics of
      tea in a tea bag. The effects of tea particle size, tea bag dipping rate, loading
      of tea granules in tea bag and tea bag shapes on infusion kinetics were
      investigated. Increase in tea loading in tea bags resulted in reduced infusion
      kinetics. Double chambered tea bag showed the highest swelling (30%) and infusion
      kinetics (8.30% Gallic acid equivalence) while single chambered tea bags showed
      the lowest kinetics, amongst the various bags studied. The swelling and infusion
      kinetics of loose tea was always faster and higher than that of tea bags. It was
      found that overall effect of percentage filling of tea granules and height of tea
      bed in a tea bag affects tea infusion kinetics the most. Weibull model was found
      to be in good agreement with the swelling data.

PMID- 28740306
TI  - Comparative study of the quality characteristics of defatted soy flour treated by
      supercritical carbon dioxide and organic solvent.
AB  - Defatted soy flour is a potential source of food protein, amino acids, ash and
      isoflavones. The supercritical carbon dioxide (SC-CO2) and a traditional organic
      solvent extraction methods were used to remove fat from soy flour, and the
      quality characteristics of a control soy flour (CSF), defatted soy flour by SC
      CO2 (DSFSC-CO2) and defatted soy flour by an organic solvent (DSF-OS) were
      compared. The SC-CO2 process was carried out at a constant temperature of 45 
      degrees C, and a pressure of 40 MPa for 3 h with a CO2 flow rate of 30 g/min. The
      DSFSC-CO2 had significantly higher protein, ash, and amino acids content than CSF
      and DSF-OS. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) analysis demonstrated that CSF and DSFSC-CO2 had protein bands of similar
      intensity and area that indicated no denaturation of protein, whereas DSF-OS
      showed diffuse bands or no bands due to protein denaturation. In addition to
      higher nutritional value and protein contents, DSFSC-CO2 showed superior
      functional properties in terms of total soluble solids content, water and oil
      absorption, emulsifying and foaming capacity. The SC-CO2 method offers a
      nutritionally and environmentally friendly alternative extraction processing
      approach for the removal of oil from high-protein food sources. It has a great
      potential for producing high-protein fat-free, and low-calorie content diet than
      the traditional organic solvent extraction method.

PMID- 28740307
TI  - Evaluations of physicochemical and anti-oxidant properties of powdered leaves
      from lotus, shepherd's purse and goldenrod in restructured duck/pork patties.
AB  - The objective of this study was to determine the effects of powdered leaves of
      lotus (LP), shepherd's purse (SP) and goldenrod (GP) on oxidation stability and
      quality characteristics of cooked duck/pork patties. Fresh duck tenderloin (M.
      pectoralis) and pork meat (M. biceps femoris, semitendinosus, and
      semimembranosus) were ground, formulated with LP, SP, GP or butylated
      hydroxytoluene (BHT), and mixed with other non-meat ingredients. The manufactured
      patties were cooked, packaged, and stored at 3  degrees C for 4 weeks. The
      patties containing 1% of LP, SP and GP had significantly lower values in redness,
      thiobarbituric acid reactive substances, conjugated dienes and total volatile
      basic nitrogen compared to control. No significant differences in sensory
      tenderness between the control and treated samples were observed. Addition of LP
      had a similar warmed-over flavor extent compared to patties with BHT. These
      results indicate that incorporation of the natural leaves could effectively
      inhibit oxidation and maintain freshness of cooked patties without any
      detrimental effects on sensory attributes during storage.

PMID- 28740308
TI  - Changes on biogenic, volatile amines and microbial quality of the blue swimmer
      crab (Portunus pelagicus) muscle during storage.
AB  - Biogenic amines (BAs) are a group of substances with low molecular weight organic
      compounds such as aliphatic, aromatic or heterocyclic structures that are
      naturally present in animal tissues. The aim of this study was to investigate the
      changes on the formation of biogenic amine, bacterial load and biochemical
      characteristics in blue swimmer crab (Portunus pelagicus) at different storage
      temperatures (4 and 20  degrees C) up to 96 h. From seven BAs only four biogenic
      amines (tryptamine, putrescine, histamine, and tyramine) were detected while, the
      cadaverine, spermidine and spermine were absent in all investigated samples.
      Histamine was the major biogenic amine formed during the storage times and
      reached the highest concentration of 7.55 +/- 0.46 mg/100 g and 17.68 +/- 1.30
      mg/100 g after 96 h at 4 and 20  degrees C, respectively. This level of histamine
      exceeded the maximum tolerance level of 5 mg/100 g. However, the proper icing
      procedure retarded the histamine effects, resulting only 7.55 mg/100 g after 96 h
      of ice storage. Spoilage indicator putrescine was only detected after 24-96 h of
      storage at 4 and 20  degrees C, respectively. The total volatile base nitrogen
      and the trimethylamine-nitrogen concentrations were considered to be reliable
      indicators of freshness index in blue swimmer crab. An aerobic mesophilic plate
      count of 6.68 and 7.31 log CFU/g were noted for crab stored in ice and ambient
      temperature after 96 h storage, respectively. It could be concluded that the
      biogenic amine forming bacteria and other susceptible perishing factors
      responsible for the biogenic amine formation could be prevented by continuous
      storage of P. pelagicus at low temperature.

PMID- 28740309
TI  - Assessment of the textural variation of iced stored Anabas testudineus (Bloch,
      1792) muscle tissue with emphasis on their collagen and myofibrillar protein
      content.
AB  - Post-mortem biochemical and physiological changes of climbing perch (Anabas
      testudineus) muscle evaluated during iced storage of 18 days compared with muscle
      protein content. Changes in the protein fractions, rigor index, pH value, water
      holding capacity, expressible water content, cook loss, textural parameters, and
      histochemical properties of the post mortem fish muscle were studied. The whole
      fish were in full rigor condition till fifth day of storage. Initial muscle pH
      value of 6.97 was dropped to 6.90 when the fish reached in full rigor condition,
      this then increased to 7.10 on the final day of storage period. The myofibrillar
      protein decreased with an initial value of 29.76% and a final value of 13.49%.
      40.27% decrease in total collagen content was observed during the storage period.
      The water holding capacity of fish muscle decreased when the fish muscle entered
      in post rigor stage while cook loss and expressible water content were
      significantly increased. The histochemical studies and textural profile analysis
      of fish muscle proved that the degradation of both collagen and myofibrillar
      protein induces the post-mortem tenderization and the resultant quality
      deterioration of iced stored Anabas testudineus fish.

PMID- 28740310
TI  - High-pressure assisted extraction of bioactive compounds from industrial
      fermented fig by-product.
AB  - High-pressure assisted extraction was employed to obtain fig by-product derived
      extracts and its impact was evaluated on antioxidant activity and total phenolic,
      tannin, and flavonoid. A Box-Behnken design was applied to evaluate the effects
      of pressure, extraction time and ethanol concentration on extractions and optimal
      conditions were estimated by response surface methodology. The correlation
      analysis of the mathematical-regression model indicated that a quadratic
      polynomial model could be employed to optimize the high pressure extraction of
      compounds. Only the models developed for total antioxidant activity by DPPH . and
      for total flavonoids presented coefficient determinations lower than 0.95. From
      response surface plots, pressure, extraction time and ethanol concentration
      showed independent and interactive effects. The optimal conditions included 600
      MPa, an extraction time between 18 and 29 min, depending on the parameter
      analyzed and a low ethanol concentration (<15%) except for flavonoids (48%). High
      pressure led to an increase of 8-13% of antioxidant activity and an increase of 8
      11% of total phenolics, flavonoids and tannins content when compared to extracts
      performed at 0.1 MPa. Analysis of variance indicated a high goodness of fit of
      the models used and the adequacy of response surface methodology for optimizing
      high pressure extraction.

PMID- 28740311
TI  - Antimicrobial resistance and typing of Salmonella isolated from street vended
      foods and associated environment.
AB  - The present study was carried out to find out the occurrence and types of
      Salmonella present in street vended foods and associated environment, and their
      resistance pattern against various antibiotics. About 1075 street vended food and
      associated environment samples were processed for isolation and confirmation of
      different Salmonella spp. by targeting gene specific invA gene and serotype
      specific Sdf I, Via B and Spy genes by PCR. Selected Salmonella isolates were
      screened for antibiotic resistance by using Baeur-Kirby disk diffusion test. Out
      of 1075 samples, only 31 (2.88%) isolates could be amplified the invA gene of
      which 19 could be recovered from meat vendors; 8 from egg vendors while remaining
      4 from milk vendors. Though, majority of Salmonella recovered from raw foods the
      ready-to-eat food like chicken gravy and rasmalai also showed its presence which
      pose a serious public health threat. Overall, 19, 6 and 1 isolates of S.
      Typhimurium, S. Enteritidis and S. Typhi could be detected by PCR while remaining
      5 isolates could not be amplified suggesting other type of Salmonella. Selected
      Salmonella isolates were completely resistance to Oxacillin (100%) followed by
      Cefoxitin (30.43%) and Ampicillin (26.10%). Thus, it is observed that the street
      vended foods of animal origin and associated environment play an important role
      in transmission of food borne pathogens including Salmonella.

PMID- 28740312
TI  - Effect of various acids on physicochemical and functional characteristics of
      gelatin from swim bladder of rohu (Labeo rohita).
AB  - Influence of various acids (acetic acid, phosphoric acid, and propionic acid) at
      different concentrations (0.05, 0.1, and 0.2 M) on the extraction yield,
      physicochemical and functional properties of gelatin from Labeo rohita swim
      bladder were investigated. Highest gelatin yield (44.22%, dry weight basis) was
      obtained in a sample prepared by without acid pretreatment (GWA) of swim bladder
      as compared to acid pretreatment counterparts. Amongst the acid pretreatments,
      propionic acid (GPrA) showed the highest gelatin yield, followed by acetic acid
      (GAA) and phosphoric acid (GPA) at all concentrations used, respectively.
      Moreover, with increased concentrations of all acids, the decrease in gelatin
      yield was observed for all the acids. GWA showed higher protein and
      hydroxyproline content than that of acid counterparts (P < 0.05). Amino acid
      analysis of gelatins showed glycine as the major amino acid in all gelatins
      followed by proline, glutamic acid and alanine, respectively. GWA showed alpha
      (alpha1 and alpha2) and beta-chains as the predominant components with low
      molecular weight peptides. However, GPrA, GAA, and GPA had alpha1 and alpha2
      dominant constituents. FTIR spectra of gelatins revealed that the loss of the
      triple-helix was found in GPA, GAA, and GPrA, compared to GWA. Among gelatin
      samples, GWA showed the highest solubility at all pH tested followed by GPrA,
      GPA, and GAA respectively. Furthermore, GWA exhibited higher emulsifying, foaming
      and gelling properties as compared to GPrA, GPA, and GAA, respectively.
      Therefore, the acid pretreatment of swim bladder had a negative impact on the
      extraction yield, physicochemical and functional properties of gelatin from rohu
      swim bladder.

PMID- 28740313
TI  - Characterization of Portuguese honey from Castelo Branco region according to
      their pollen spectrum, physicochemical characteristics and mineral contents.
AB  - The aim of this work was to evaluate the quality of 16 honey samples from Castelo
      Branco region (Portugal). Twelve are monofloral from Calluna vulgaris, Erica,
      Lavandula, Echium and Campanula. The mean values obtained for physicochemical
      parameters were: 3.82 pH; 16.80% moisture; 81.6 degrees Brix; 0.21% ash; 357.6
      MUS cm-1 electrical conductivity; 33.7 meq/kg free acidity; 5.7 meq/kg lactonic
      acidity; 39.3 meq/kg total acidity; 9.11 mg/kg HMF; 21.3 IN invertase and 9.0
      degrees  Gothe for diastase activities. The results indicate a good quality,
      adequate processing, good maturity and freshness of honey. Additionally, the
      determination of mineral contents revealed that the K was the major element. Mean
      values obtained were (mg/kg): Ca, 28.36; K, 701.87; Mg, 74.00; Na, 31.04; Fe,
      097; Cu, 0.65; Zn, 1.23; Mn, 2.78 and P, 48.80. Among the overall determined
      parameters, CB2 stands out by its high values in minerals, pH, moisture, ash,
      electrical conductivity and enzyme activity.

PMID- 28740314
TI  - A neural network based model to analyze rice parboiling process with small
      dataset.
AB  - In this study, milling recovery, head rice yield, degree of milling and whiteness
      were utilized to characterize the milling quality of Tarom parboiled rice
      variety. The parboiled rice was prepared with three soaking temperatures and
      steaming times. Then the samples were dried to three levels of final moisture
      contents [8, 10 and 12% (w.b)]. Modeling of process and validating of the results
      with small dataset are always challenging. So, the aim of this study was to
      develop models based on the milling quality data in parboiling process by means
      of multivariate regression and artificial neural network. In order to validate
      the neural network model with a little dataset, K-fold cross validation method
      was applied. The ANN structure with one hidden layer and Tansig transfer function
      by 18 neurons in the hidden layer was selected as the best model in this study.
      The results indicated that the neural network could model the parboiling process
      with higher degree of accuracy. This method was a promising procedure to create
      accuracy and can be used as a reliable model to select the best parameters for
      the parboiling process with little experiment dataset.

PMID- 28740315
TI  - Importance of the gastrointestinal life cycle of Bacillus for probiotic
      functionality.
AB  - Bacillus spp. are widely used in animal production for their probiotic
      properties. In many animal species, feed supplementation with specific Bacillus
      strains can provide numerous benefits including improvement in digestibility, the
      gut microbiota and immune modulation, and growth performance. Bacilli are fed to
      animals as spores that can sustain the harsh feed processing and long storage.
      However, the spores are metabolically quiescent and it is widely accepted that
      probiotics should be in a metabolically active state to perform certain probiotic
      functions like secretion of antimicrobial compounds and enzymes, synthesis of
      short chain fatty acids, and competition for essential nutrients. These functions
      should become active in the host gastrointestinal tract (GIT) soon after
      digestion of spores in order to contribute to microbiota and host metabolism.
      Considering that bacterial spores are metabolically dormant and many health
      benefits are provided by vegetative cells, it is of particular interest to
      discuss the life cycle of Bacillus in animal GIT. This review aims to capture the
      main characteristics of spores and vegetative cells and to discuss the latest
      knowledge in the life cycle of beneficial Bacillus in various intestinal
      environments. Furthermore, we review how the life cycle may influence probiotic
      functions of Bacillus and their benefits for human and animal health.

PMID- 28740317
TI  - HS-GC-MS-O analysis and sensory acceptance of passion fruit during maturation.
AB  - The odor-active compounds of the conventional yellow passion fruit influence the
      aroma during ripeness and the acceptance of the juice. HS-GC-MS and GC-OSME
      analysis and sensory acceptance of the conventional passion fruit from different
      stages of ripeness were studied to characterize the aroma of the fruit and, aroma
      and flavor of the juice. Ethyl butanoate, ethyl hexanoate and propyl acetate
      showed high odoriferous importance in the passion fruit from the 1/3 yellow skin
      color. Cis-3-hexen-1-ol and diethyl carbonate plus the odor-active compounds from
      the 1/3 yellow skin color showed high odoriferous importance in the 2/3 yellow
      skin color, and butyl acetate and alpha-terpineol plus the same odor-active
      compounds from 2/3 were the most important for the 3/3 yellow skin color. There
      was difference in the aroma and flavor of the juices, with higher acceptance
      means for the passion fruit from the 3/3 yellow skin color. The passion fruit
      volatile compounds peak area, odoriferous intensity and sensory acceptance of the
      juices increased during ripeness, indicating that the conventional passion fruit
      characteristic aroma is completely expressed when the fruit reaches the whole
      maturation, at the 3/3 yellow skin color.

PMID- 28740316
TI  - Impact of oral processing on texture attributes and taste perception.
AB  - Mastication is the first step of food digestion, where foods are broken down and
      simultaneously impregnated by saliva resulting in the formation of semi-fluids
      known as food boluses. This review focuses on the impact of oral processing on
      texture attributes and taste perception. The article describes the oral actions
      in which texture characteristic are measured for the critical conditions that
      trigger swallowing. Taste perception also plays a key role in oral processing and
      oral sensations. There are still challenges in terms of determining different
      oral physiological characteristics. These include individual chewing behavior
      regardless of the temporal aspects of dominant processes of comminution,
      insalivation, bolus formation and swallowing. A comprehensive approach is
      essential to process favorable foods with respect to the food properties of
      texture and taste.

PMID- 28740318
TI  - Increased advanced glycation end product specific fluorescence in repeatedly
      heated used cooking oil.
AB  - Repeated heating of cooking oils is known to cause their degradation and
      generation of toxins. Dietary Advanced glycation end products (dAGEs) are formed
      when the foods are cooked in dry heat at very high temperatures. dAGEs are
      believed to contribute significantly to total pool of AGEs in body. In this
      study, cooking oil samples used for frying snacks were collected from 102 shops.
      AGEs were extracted using Aqueous-TCA-chloroform method. Fluorescent AGE levels
      were determined using a fluorescence spectrophotometer and compared with AGEs in
      corresponding fresh oil samples collected from same shops. Palm oil was most
      commonly (62.5%) used for cooking. Most of the samples were subjected to several
      rounds of heating (1-6). AGE specific fluorescence (ASF) in used oil (range = 8.5
      745.11) samples was found to be significantly higher in 88/102 as compared to the
      corresponding fresh oil samples. Treatment with inhibitors like lime concentrate
      and vitamin C decreased ASF (10/14 and 10/11 samples respectively) of the used
      oils. The results suggest that cooking oil subjected to repeated heating can
      contribute to increase in fluorescent AGEs in diet. Simple practices like liberal
      use of common household substances like lime concentrate may help to reduce these
      in fried food.

PMID- 28740319
TI  - Antibacterial activity of Timsen(r) (n-alkyl dimethyl benzyl ammonium chloride
      40%) in scalding and precooling water in poultry slaughterhouses.
AB  - The objective of this study was to evaluate the efficacy of a product based on n
      alkyl dimethyl benzyl ammonium chloride-40%, marketed as Timsen(r), during
      scalding and precooling of poultry carcasses in slaughterhouses. To this end,
      three poultry slaughterhouses (A, B and C) were evaluated. The product was added
      (200 ppm) to the scalding (58  degrees C) and precooling water (4  degrees C),
      and microbiological analyses were performed of the water and the poultry
      carcasses before and after Timsen(r) addition. The product controlled the
      multiplication of aerobic mesophilic microorganisms, both in the scalding as in
      the precooling water. In a comparison of carcasses soaked in Timsen(r)-treated
      scalding and precooling water with carcasses soaked in untreated water, the count
      of aerobic mesophilic microorganisms in the later was higher and thermotolerant
      coliform was not detected in samples of carcasses soaked in Timsen(r)-treated
      water. When the scalding and precooling water was not treated with the product,
      Listeria spp. was isolated from poultry carcasses of two slaughterhouses (A and
      C), while these microorganisms were not detected when Timsen(r) was applied. The
      use of Timsen(r) in the scalding and precooling water enhanced the safety and
      control microbial contamination of poultry carcasses.

PMID- 28740320
TI  - Rigorous evaluation of chemical measurement uncertainty: Liquid chromatographic
      analysis methods using detector response factor calibration.
AB  - Chemical measurement methods are designed to promote accurate knowledge of a
      measurand or system. As such, these methods often allow elicitation of latent
      sources of variability and correlation in experimental data. They typically
      implement measurement equations that support quantification of effects associated
      with calibration standards and other known or observed parametric variables.
      Additionally, multiple samples and calibrants are usually analyzed to assess
      accuracy of the measurement procedure and repeatability by the analyst. Thus, a
      realistic assessment of uncertainty for most chemical measurement methods is not
      purely bottom-up (based on the measurement equation) or top-down (based on the
      experimental design), but inherently contains elements of both. Confidence in
      results must be rigorously evaluated for the sources of variability in all of the
      bottom-up and top-down elements. This type of analysis presents unique challenges
      due to various statistical correlations among the outputs of measurement
      equations. One approach is to use a Bayesian hierarchical (BH) model which is
      intrinsically rigorous, thus making it a straightforward method for use with
      complex experimental designs, particularly when correlations among data are
      numerous and difficult to elucidate or explicitly quantify. In simpler cases,
      careful analysis using GUM Supplement 1 (MC) methods augmented with random
      effects meta analysis yields similar results to a full BH model analysis. In this
      article we describe both approaches to rigorous uncertainty evaluation using as
      examples measurements of 25-hydroxyvitamin D3 in solution reference materials via
      liquid chromatography with UV absorbance detection (LC-UV) and liquid
      chromatography mass spectrometric detection using isotope dilution (LC-IDMS).

PMID- 28740321
TI  - Beliefs about savoring in older adulthood: Aging and perceived health affect
      temporal components of perceived savoring ability.
AB  - The ability to savor positive life events is associated with higher emotional
      well-being; however, few studies have examined savoring ability in older adults.
      The present study used a longitudinal design to examine changes in perceived
      savoring abilities and associations with perceived health in older adulthood.
      Older adults (N=131) reported on beliefs about savoring and perceived health at
      baseline and 21/2 years later. Perceived anticipation (savoring the future) and
      reminiscing (savoring the past) abilities declined from baseline to follow-up.
      Better perceived health at baseline predicted greater perceived reminiscing and
      anticipation abilities at follow-up. Greater perceived ability to savor the
      present moment at baseline predicted better perceived health at follow-up. Aging
      and poorer health focus older adults' thoughts on present-moment pleasures, which
      may benefit health, but may also lead to reductions in perceived anticipation and
      reminiscing abilities.

PMID- 28740322
TI  - Occupational Hearing Loss from Non-Gaussian Noise.
AB  - Noise levels are truly continuous in relatively few occupations, with some degree
      of intermittency the most common condition. The sound levels of intermittent
      noise are often referred to as non-Gaussian in that they are not normally
      distributed in the time domain. In some conditions, intermittent noise affects
      the ear differently from continuous noise, and it is this assumption that
      underlies the selection of the 5-dB exchange rate (ER). The scientific and
      professional communities have debated this assumption over recent decades. This
      monograph explores the effect of non-Gaussian noise on the auditory system. It
      begins by summarizing an earlier report by the same author concentrating on the
      subject of the ER. The conclusions of the earlier report supported the more
      conservative 3-dB ER with possible adjustments to the permissible exposure limit
      for certain working conditions. The current document has expanded on the earlier
      report in light of the relevant research accomplished in the intervening decades.
      Although some of the animal research has supported the mitigating effect of
      intermittency, a closer look at many of these studies reveals certain weaknesses,
      along with the fact that these noise exposures were not usually representative of
      the conditions under which people actually work. The more recent animal research
      on complex noise shows that intermittencies do not protect the cochlea and that
      many of the previous assumptions about the ameliorative effect of intermittencies
      are no longer valid, lending further support to the 3-dB ER. The neurologic
      effects of noise on hearing have gained increasing attention in recent years
      because of improvements in microscopy and immunostaining techniques. Animal
      experiments showing damage to auditory synapses from noise exposures previously
      considered harmless may signify the need for a more conservative approach to the
      assessment of noise-induced hearing loss and consequently the practice of hearing
      conservation programs.

PMID- 28740323
TI  - And the Results are In!!!

PMID- 28740324
TI  - Microhardness evaluations of CAD/CAM ceramics irradiated with CO2 or Nd:YAP
      laser.
AB  - BACKGROUND AND AIMS: The aim of this study was to measure the microhardness
      values of irradiated computer-aided design/computer-aided manufacturing (CAD/CAM)
      ceramics surfaces before and after thermal treatment. MATERIALS AND METHODS:
      Sixty CAD/CAM ceramic discs were prepared and grouped by material, i.e. lithium
      disilicate ceramic (Emax CAD) and zirconia ceramic (Emax ZirCAD). Laser
      irradiation at the material surface was performed with a carbon dioxide laser at
      5 Watt (W) or 10 W power in continuous mode (CW mode), or with a
      neodymium:yttrium aluminum perovskite (Nd:YAP) laser at 10 W on graphite and non
      graphite surfaces. Vickers hardness was tested at 0.3 kgf for lithium disilicate
      and 1 kgf for zirconia. RESULTS: Emax CAD irradiated with CO2 at 5 W increased
      microhardness by 6.32 GPa whereas Emax ZirCAD irradiated with Nd:YAP decreased
      microhardness by 17.46 GPa. CONCLUSION: CO2 laser effectively increases the
      microhardness of lithium disilicate ceramics (Emax CAD).

PMID- 28740325
TI  - Low Level Laser Therapy in patients with chronic foot and ankle joint pain.
AB  - BACKGROUND AND AIMS: Chronic foot and ankle joint pain is one of the most
      frequent complaints which is regularly seen in the out-patient clinic of our
      medical institute. In previous studies we have reported on the benefits of low
      level laser therapy (LLLT) for chronic pain in the elbow, hand, finger and the
      lower back. The present study examined the effects of LLLT on chronic foot and
      ankle joint pain. MATERIALS AND METHODS: Over the past 5 years, 17 subjects
      visited the out-patient clinic with complaints of chronic foot and ankle joint
      pain of a variety of aetiologies. The patients received LLLT using a 1000 mW semi
      conductor laser device, delivering 20.1 J/cm2 per point at 830 nm in continuous
      wave. Each patient was given four shots per session per foot twice a week for 4
      weeks. RESULTS: A visual analogue scale (VAS) was used to determine the effects
      of LLLT for the chronic pain and after the end of the treatment regimen a
      significant improvement was observed (p < 0.01). All but 2 of the patients showed
      improvement: excellent (2) and good (13). After treatment, no significant
      differences were observed in the ankle joint range of motion, however.
      Discussions with the patients revealed that it was important for them to learn
      how to avoid overuse of the ankle when walking, poor walking posture and a poor
      pacing technique that would caused them foot and ankle pain in everyday life.
      Following these postural guidelines could ensure continuous benefits from the
      treatment. CONCLUSION: The present study demonstrated that LLLT was an effective
      form of treatment for chronic foot and ankle joint pain, in conjunction with
      postural education during all activities of daily living.

PMID- 28740326
TI  - On-line laser radiation controlled to the removal of adhesive on teeth after
      bracket debonding.
AB  - BACKGROUND AND AIMS: After bracket debonding a correct removal of the adhesive
      from tooth surfaces without causing any iatrogenic damage to the enamel is
      needed. However, conventional techniques do not allow a selective removal
      process. The present article focuses on the removal of adhesive on teeth after
      bracket debonding by using laser radiation at 355 nm (third harmonic wavelength
      of a Q-switched Nd:YAG). MATERIAL AND METHODS: Brackets were bonded to 10
      extracted human premolars from young patients and removed after a storage period
      of 2 months. As real-time diagnostic technique, laser-induced breakdown
      spectroscopy (LIBS) elemental analysis was applied for precisely controlling the
      removal of the adhesive and morphological analysis of the etched surfaces was
      carried out by scanning electron microscopy (SEM). RESULTS: LIBS technique
      allowed an on-line precise control in the adhesive removal process. SEM analysis
      revealed the capability of the 355 nm UV laser radiation to complete the removal
      of the adhesive on the tooth with no signs of damage on the enamel. CONCLUSION:
      Laser ablation process at 355 nm monitored by the LIBS technique allows to carry
      out efficient removal of the adhesive on teeth.

PMID- 28740327
TI  - Static and dynamic modes of 810 nm diode laser hair removal compared: A clinical
      and histological study.
AB  - BACKGROUND AND AIMS: Laser hair removal has recently become a major indication.
      Diode lasers have become commercially available offering two modes of
      application: a stamping or static mode, and a dynamic mode whereby the handpiece
      is continuously moved across the target tissue. The present study was designed to
      compare the efficacy of these two approaches clinically and histologically.
      SUBJECTS AND METHODS: Twenty-five subjects participated in the study, 12 males
      and 13 females, ages ranging from 20 to 57 yr (Mean age 41.6 yr). A baseline hair
      count was performed on both the target areas. The ms-pulsed diode laser delivered
      810 nm via a handpiece with a cooled tip, offering both static and dynamic modes
      which were used on the subjects' left and right crura, respectively. Pain during
      treatment was assessed using a visual analog scale (VAS) and gross inspection was
      performed immediately after treatment for any abnormality in the treated skin.
      Hair counts were performed on both crura at 1 and 3 months after the treatment,
      and compared with the baseline counts. Biopsies were performed in the dynamic
      mode treated skin at baseline and at 1 month after the treatment, and assessed
      with light microscopy, immunohistochemistry and transmission electron microscopy
      (TEM). RESULTS: All subjects completed the study. Compared with baseline, hair
      counts were significantly lower at 1 and 3 months post-treatment with no
      significant difference between the static and dynamic laser depilation modes, nor
      in the severity of the pain experienced during the procedure. Histologically,
      degenerative changes in the hair follicles were noted immediately after laser
      treatment. At one month, cystic formation was seen in the hair follicles showing
      a strong tendency towards apoptotic cell death. CONCLUSIONS: With the diode laser
      system and at the parameters used in the present study, high depilation efficacy
      was seen with no significant difference between the static and dynamic modes.
      Interestingly, good long-term depilation is probably a result of induced
      apoptotic cell death in the follicles rather than any other mechanism.

PMID- 28740328
TI  - Assessment of equivalence of adipose tissue treatment with a noncontact field RF
      system delivering 200 W for 30 min and 300 W for 20 min: An in vivo porcine
      study.
AB  - BACKGROUND AND AIMS: Abdominal circumferential reduction with noncontact high
      frequency apoptosis-inducing field RF (AiRF) is becoming very popular. The
      present study compared the treatment results from two different sets of
      parameters giving the same dose from the same system in an in vivo porcine model.
      MATERIALS AND METHODS: Two 10 cm * 10 cm areas were symmetrically marked on both
      sides of the midline (total of 4 areas) over the rectus abdominis muscle of two
      anesthetized female micropigs. In Animal A (G1), 27.12 MHz AiRF treatment was
      given at 200 W for 30 min, and 300 W for 20 min in Animal B (G2). Four sessions
      were performed at weekly intervals. Gross observation by a veterinary specialist
      was performed on a daily basis. Temperature measurements (fat and skin), clinical
      photography and ultrasound imaging were carried out at each session. In addition,
      blood chemistry was performed before each session to check lipid levels, any
      adverse changes in markers for liver damage in addition to an enzyme-linked
      immunosorbent assay (ELISA) for raised levels of TNF-alpha and IL-1beta. Biopsies
      were taken and routinely processed for hematoxylin and eosin, Toluidine blue and
      oil red O stains to examine for tissue damage at baseline and after each
      treatment. TUNEL assays were performed to check of apoptotic-related DNA damage.
      Follow-up assessments included photography, ultrasound, ELISA tests and biopsies
      which were taken regularly up to 90 days after the final treatment. RESULTS: The
      maximum adipose tissue temperatures at and over the apoptotic threshold of 43
      degrees C were reached and maintained in both G1 and G2. The skin surface
      temperature was slightly higher in G2 after 20 min than in G1 after 30 min, but
      was still below 43 degrees C. Gross and magnified observation revealed no
      appreciable differences or thermally-mediated damage between the skin of either
      of the two groups after the treatments or during the 90-day follow-up period. No
      lasting erythema or any other adverse event was seen in either group. The liver
      enzyme markers showed very similar patterns over the 4 weeks of treatment
      compared with baseline with no levels outside of the normal range. Triglycerides
      were all within normal rage with no significant differences between the groups.
      Remarkably similar patterns were noted for the ELISAs in both groups performed
      over the 4 weeks of treatment and at periods during the 90-day follow-up with no
      notable abnormal changes in levels. Staining patterns for both G1 and G2
      specimens were similar for all stain types during treatment and the 90-day follow
      up, showing decreased numbers of adipocytes by the 90-day point. The ultrasound
      findings revealed a 44.8% and 55.6% decrease in the adipose layer for G1 and G2,
      respectively, at the 90-day assessment. CONCLUSIONS: The 200 W AiRF treatment for
      30 min (G1) and the 300 W AiRF treatment for 20 min (G2) produced very similar
      results in the porcine model for all assessments and at all assessment points
      during and up to 90 days after treatment, with slightly better findings suggested
      for G2. Based on the above findings, the two different settings, delivering the
      same dose, produced good results with no skin damage and no adverse events. This
      has implications in busy clinics for AiRF treatment, where the shorter treatment
      time could represent time saving for the clinic and the patient without
      compromising safety and giving equal if not better efficacy.

PMID- 28740329
TI  - 940 nm Diode Laser assisted excision of Peripheral Ossifying Fibroma in a
      neonate.
AB  - BACKGROUND: Peripheral ossifying fibroma associated with neonatal tooth
      extraction is a rare, benign reactive lesion, but its nature and location often
      scares the patient & parents for possibility of neoplasm. A high recurrence rate
      makes its histopathological examination and long term follow up important. CASE
      REPORT: A 2 months old boy presented with enlarging soft tissue growth on the
      anterior mandibular ridge. The history revealed extraction of two neonatal teeth
      at 2 weeks of age. Lesion was excised using 940 nm diode laser and
      histopathological examination revealed hypercellularity and prominent dystrophic
      calcification, confirming it to be Peripheral Ossifying Fibroma. There was no
      recurrence after 18 months follow up. CONCLUSION: Paediatric dentists should be
      aware of possible outcomes of natal and neonatal teeth extraction and
      histopathological features of soft tissue lesions in neonates and infants. This
      report also highlights that 940 nm diode laser can be safely used for minor oral
      soft tissue surgeries in neonates and infants.

PMID- 28740330
TI  - Soft tissue molding technique in cleft lip and palate patient using laser surgery
      in combination with orthodontic appliance: A case report.
AB  - BACKGROUND: Although surgical treatment protocols for cleft lip and palate
      patients have been established, many patients still have some soft tissue defects
      after complete healing from surgical interventions. These are excess soft tissue,
      high attached fraena and firmed tethering scares. These soft tissue defects
      resulted shallowing of vestibule, restricted tooth movement, compromised
      periodontal health and trended to limit the maxillary growth. The aim of this
      case report was to present a method of correcting soft tissue defects after
      conventional surgery in cleft lip and palate patient by using combined laser
      surgery and orthodontic appliance. CASE REPORT: A bilateral cleft lip and palate
      patient with a clinical problem of shallow upper anterior vestibule after
      alveolar bone graft received a vestibular extension by using CO2 laser with
      ablation and vaporization techniques at 4 W and continuous wave. A customized
      orthodontic appliance, called a buccal shield, was placed immediately after
      surgery and retained for 1 month to 3 months until complete soft tissue healing.
      The procedures were performed 2 episodes. Both interventions used the same CO2
      laser procedure. The first treatment resulted in partial re-attachment of soft
      tissue at surgical area. The second laser operation with the proper design of
      buccal shield providing passive contact with more extended flange resulting in a
      favorable outcome from 1 year follow up. Then the corrective orthodontic
      treatment could be continued effectively. CONCLUSION: The CO2 laser surgery was a
      proper treatment for correcting soft tissue defects and the design of buccal
      shield was a key for success in molding surgical soft tissue.

PMID- 28740331
TI  - Mixture of autoregressive modeling orders and its implication on single trial EEG
      classification.
AB  - Autoregressive (AR) models are of commonly utilized feature types in
      Electroencephalogram (EEG) studies due to offering better resolution, smoother
      spectra and being applicable to short segments of data. Identifying correct AR's
      modeling order is an open challenge. Lower model orders poorly represent the
      signal while higher orders increase noise. Conventional methods for estimating
      modeling order includes Akaike Information Criterion (AIC), Bayesian Information
      Criterion (BIC) and Final Prediction Error (FPE). This article assesses the
      hypothesis that appropriate mixture of multiple AR orders is likely to better
      represent the true signal compared to any single order. Better spectral
      representation of underlying EEG patterns can increase utility of AR features in
      Brain Computer Interface (BCI) systems by increasing timely & correctly
      responsiveness of such systems to operator's thoughts. Two mechanisms of
      Evolutionary-based fusion and Ensemble-based mixture are utilized for identifying
      such appropriate mixture of modeling orders. The classification performance of
      the resultant AR-mixtures are assessed against several conventional methods
      utilized by the community including 1) A well-known set of commonly used orders
      suggested by the literature, 2) conventional order estimation approaches (e.g.,
      AIC, BIC and FPE), 3) blind mixture of AR features originated from a range of
      well-known orders. Five datasets from BCI competition III that contain 2, 3 and 4
      motor imagery tasks are considered for the assessment. The results indicate
      superiority of Ensemble-based modeling order mixture and evolutionary-based order
      fusion methods within all datasets.

PMID- 28740333
TI  - Mold Alkaloid Cytochalasin D Modifies the Morphology and Secretion of fMLP-, LPS
      , or PMA-Stimulated Neutrophils upon Adhesion to Fibronectin.
AB  - Neutrophils play an essential role in innate immunity due to their ability to
      migrate into infected tissues and kill microbes with bactericides located in
      their secretory granules. Neutrophil transmigration and degranulation are tightly
      regulated by actin cytoskeleton. Invading pathogens produce alkaloids that cause
      the depolymerization of actin, such as the mold alkaloid cytochalasin D. We
      studied the effect of cytochalasin D on the morphology and secretion of fMLP-,
      LPS-, or PMA-stimulated human neutrophils upon adhesion to fibronectin. Electron
      microscopy showed that the morphology of the neutrophils adherent to fibronectin
      in the presence of various stimuli differed. But in the presence of cytochalasin
      D, all stimulated neutrophils exhibited a uniform nonspread shape and developed
      thread-like membrane tubulovesicular extensions (cytonemes) measuring 200 nm in
      diameter. Simultaneous detection of neutrophil secretory products by mass
      spectrometry showed that all tested stimuli caused the secretion of MMP-9, a key
      enzyme in the neutrophil migration. Cytochalasin D impaired the MMP-9 secretion
      but initiated the release of cathepsin G and other granular bactericides,
      proinflammatory agents. The release of bactericides apparently occurs through the
      formation, shedding, and lysis of cytonemes. The production of alkaloids which
      modify neutrophil responses to stimulation via actin depolymerization may be part
      of the strategy of pathogen invasion.

PMID- 28740332
TI  - A Protective Role of Glibenclamide in Inflammation-Associated Injury.
AB  - Glibenclamide is the most widely used sulfonylurea drug for the treatment of type
      2 diabetes mellitus (DM). Recent studies have suggested that glibenclamide
      reduced adverse neuroinflammation and improved behavioral outcomes following
      central nervous system (CNS) injury. We reviewed glibenclamide's anti
      inflammatory effects: abundant evidences have shown that glibenclamide exerted an
      anti-inflammatory effect in respiratory, digestive, urological, cardiological,
      and CNS diseases, as well as in ischemia-reperfusion injury. Glibenclamide might
      block KATP channel, Sur1-Trpm4 channel, and NOD-like receptor pyrin domain
      containing 3 (NLRP3) inflammasome activation, decrease the production of
      proinflammatory mediators (TNF-alpha, IL-1beta, and reactive oxygen species), and
      suppress the accumulation of inflammatory cells. Glibenclamide's anti
      inflammation warrants further investigation.

PMID- 28740335
TI  - Challenges of modern day transition care in inflammatory bowel disease: From
      inflammatory bowel disease to biosimilars.
AB  - In this article we discuss the challenges of delivering a high quality Transition
      care. A good understanding of the adolescent needs with good communication
      between Transition care physicians and the patient is essential for good
      continuity of care. Despite availability of several guidelines, one model doesn't
      fit all and any transition service development should be determined by the local
      need and available healthcare facilities.

PMID- 28740334
TI  - Cytokines in Endocrine Dysfunction of Plasma Cell Disorders.
AB  - Monoclonal gammopathies (MG) are classically associated with lytic bone lesions,
      hypercalcemia, anemia, and renal insufficiency. However, in some cases, symptoms
      of endocrine dysfunction are more prominent than these classical signs and
      misdiagnosis can thus be possible. This concerns especially the situation where
      the presence of M-protein is limited and the serum protein electrophoresis (sPEP)
      appears normal. To understand the origin of the endocrine symptoms associated
      with MG, we overview here the current knowledge on the complexity of interactions
      between cytokines and the endocrine system in MG and discuss the perspectives for
      both the diagnosis and treatments for this class of diseases. We also illustrate
      the role of major cytokines and growth factors such as IL-6, IL-1beta, TNF-alpha,
      and VEGF in the endocrine system, as these tumor-relevant signaling molecules not
      only help the clonal expansion and invasion of the tumor cells but also influence
      cellular metabolism through autocrine, paracrine, and endocrine mechanisms. We
      further discuss the broader impact of these tumor environment-derived molecules
      and proinflammatory state on systemic hormone signaling. The diagnostic
      challenges and clinical work-up are illustrated from the point of view of an
      endocrinologist.

PMID- 28740336
TI  - Expression and role of nuclear receptor coregulators in colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most common human cancers and the cause of
      about 700000 deaths per year worldwide. Deregulation of the WNT/beta-catenin
      pathway is a key event in CRC initiation. This pathway interacts with other
      nuclear signaling pathways, including members of the nuclear receptor superfamily
      and their transcription coregulators. In this review, we provide an overview of
      the literature dealing with the main coactivators (NCoA-1 to 3, NCoA-6, PGC1
      alpha, p300, CREBBP and MED1) and corepressors (N-CoR1 and 2, NRIP1 and MTA1) of
      nuclear receptors and summarize their links with the WNT/beta-catenin signaling
      cascade, their expression in CRC and their role in intestinal physiopathology.

PMID- 28740337
TI  - Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut
      microbiota modulation.
AB  - Antibiotics are usually prescribed to cure infections but they also have
      significant modulatory effects on the gut microbiota. Several alterations of the
      intestinal bacterial community have been reported during antibiotic treatment,
      including the reduction of beneficial bacteria as well as of microbial alpha
      diversity. Although after the discontinuation of antibiotic therapies it has been
      observed a trend towards the restoration of the original condition, the new
      steady state is different from the previous one, as if antibiotics induced some
      kind of irreversible perturbation of the gut microbial community. The poorly
      absorbed antibiotic rifaximin seem to be different from the other antibiotics,
      because it exerts non-traditional effects additional to the
      bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to
      reduce bacterial virulence and translocation, has anti-inflammatory properties
      and has been demonstrated to positively modulate the gut microbial composition.
      Animal models, culture studies and metagenomic analyses have demonstrated an
      increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus
      abundance after rifaximin treatment, probably consequent to the induction of
      bacterial resistance, with no major change in the overall gut microbiota
      composition. Antibiotics are therefore modulators of the symbiotic relationship
      between the host and the gut microbiota. Specific antibiotics, such as rifaximin,
      can also induce eubiotic changes in the intestinal ecosystem; this additional
      property may represent a therapeutic advantage in specific clinical settings.

PMID- 28740338
TI  - Localization and role of metabotropic glutamate receptors subtype 5 in the
      gastrointestinal tract.
AB  - Metabotropic glutamate receptor subtype 5 (mGluR5) is a Group I mGlu subfamily of
      receptors coupled to the inositol trisphosphate/diacylglycerol pathway. Like
      other mGluR subtypes, mGluR5s contain a phylogenetically conserved, extracellular
      orthosteric binding site and a more variable allosteric binding site, located on
      the heptahelical transmembrane domain. The mGluR5 receptor has proved to be a key
      pharmacological target in conditions affecting the central nervous system (CNS)
      but its presence outside the CNS underscores its potential role in pathologies
      affecting peripheral organs such as the gastrointestinal (GI) tract and accessory
      digestive organs such as the tongue, liver and pancreas. Following identification
      of mGluR5s in the mouth, various studies have subsequently demonstrated its
      involvement in mechanical allodynia, inflammation, pain and oral cancer. mGluR5
      expression has also been identified in gastroesophageal vagal pathways. Indeed,
      experimental and human studies have demonstrated that mGluR5 blockade reduces
      transient lower sphincter relaxation and reflux episodes. In the intestine,
      mGluR5s have been shown to be involved in the control of intestinal inflammation,
      visceral pain and the epithelial barrier function. In the liver, mGluR5s have a
      permissive role in the onset of ischemic injury in rat and mice hepatocytes.
      Conversely, livers from mice treated with selective negative allosteric
      modulators and mGluR5 knockout mice are protected against ischemic injury.
      Similar results have been observed in experimental models of free-radical injury
      and in vivo mouse models of acetaminophen intoxication. Finally, mGluR5s in the
      pancreas are associated with insulin secretion control. The picture is, however,
      far from complete as the review attempts to establish in particular as regards
      identifying specific targets and innovative therapeutic approaches for the
      treatment of GI disorders.

PMID- 28740339
TI  - Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury.
AB  - AIM: To investigate the hypothesis that treatment with dimethyl fumarate (DMF)
      may ameliorate liver ischemia/reperfusion injury (I/RI). METHODS: Rats were
      divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was
      orally administered for 2 d before the procedure. The CTL and DMF rats were
      subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine
      aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate
      (ATP), NO * metabolites, anti-oxidant enzyme expression level, anti-inflammatory
      effect, and anti-apoptotic effect were determined. RESULTS: Histological tissue
      damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 +/- 0;
      CTL: 9.3 +/- 0.5; DMF: 2.5 +/- 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P <
      0.0001). This effect was associated with significantly lower serum ALT (DMF 5026
      +/- 2305 U/L vs CTL 10592 +/- 1152 U/L, P = 0.04) and MDA (DMF 18.2 +/- 1.4
      MUmol/L vs CTL 26.0 +/- 1.0 MUmol/L, P = 0.0009). DMF effectively improved the
      ATP content (DMF 20.3 +/- 0.4 nmol/mg vs CTL 18.3 +/- 0.6 nmol/mg, P = 0.02),
      myeloperoxidase activity (DMF 7.8 +/- 0.4 mU/mL vs CTL 6.0 +/- 0.5 mU/mL, P =
      0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 +/-
      0.05-fold vs 0.17 +/- 0.06-fold, P = 0.02). The higher expression levels of anti
      oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and
      lower levels of key inflammatory mediators (nuclear factor-kappa B and
      cyclooxygenase-2 were confirmed in the DMF group. CONCLUSION: DMF improved the
      liver function and the anti-oxidant and inflammation status following I/RI.
      Treatment with DMF could be a promising strategy in patients with liver I/RI.

PMID- 28740340
TI  - Enhanced electrogastrography: A realistic way to salvage a promise that was never
      kept?
AB  - AIM: To enhance the clinical utility of electrogastrography (EGG), which has been
      recorded since 1922, but is clinically unutilized. METHODS: An innovative method
      to salvage the promise of EGG is proposed by introducing a preliminary procedure,
      while maintaining the electrodes, standardized equipment, and signal processing
      utilized in the well-established EGG testing of today. The proposed enhanced EGG
      (EEGG) protocol involves swallowing an ingestible capsule containing miniature
      electronic oscillator embedded in an expandable, self-disintegratable,
      biocompatible pseudobesoar residing in the stomach for the duration of the test.
      The benefits of the proposed approach are outlined, tested and discussed in
      details. RESULTS: Experiments were performed on eight mongrel dogs (6F, 4M, 23.8
      +/- 3.3 kg). Four were administered an active EEGG capsule, while the rest were
      given a deactivated (battery removed) capsule. Pharmacologically facilitated
      gastric motility revealed a significant (P < 0.01) Pearson correlation between
      gastric motility indices obtained by force transducers implanted directly on the
      stomach, and the motility indices obtained by EEGG. A particular emphasis was
      made on preserving standard EGG-related hardware and software in order to
      facilitate the introduction of the proposed EEGG in environments which already
      utilize standard EGG testing. The expanded intragastric pseudobezoar containing
      the miniature electronic oscillator was retained during the tests, and could be
      disintegrated on demand. CONCLUSION: Enhancing standard EGG by an ingestible,
      self-expanding and self-disintegrating pseudobesoar containing a miniature
      electronic oscillator can be an important avenue for clinical applicability of
      this test.

PMID- 28740341
TI  - Glutamine prevents oxidative stress in a model of portal hypertension.
AB  - AIM: To evaluate the protective effects of glutamine in a model of portal
      hypertension (PH) induced by partial portal vein ligation (PPVL). METHODS: Male
      Wistar rats were housed in a controlled environment and were allowed access to
      food and water ad libitum. Twenty-four male Wistar rats were divided into four
      experimental groups: (1) control group (SO) - rats underwent exploratory
      laparotomy; (2) control + glutamine group (SO + G) - rats were subjected to
      laparotomy and were treated intraperitoneally with glutamine; (3) portal
      hypertension group (PPVL) - rats were subjected to PPVL; and (4) PPVL + glutamine
      group (PPVL + G) - rats were treated intraperitoneally with glutamine for seven
      days. Local injuries were determined by evaluating intestinal segments for
      oxidative stress using lipid peroxidation and the activities of glutathione
      peroxidase (GPx), endothelial nitric oxide synthase (eNOS) and inducible nitric
      oxide synthase (iNOS) after PPVL. RESULTS: Lipid peroxidation of the membrane was
      increased in the animals subjected to PH (P < 0.01). However, the group that
      received glutamine for seven days after the PPVL procedure showed levels of lipid
      peroxidation similar to those of the control groups (P > 0.05). The activity of
      the antioxidant enzyme GTx was decreased in the gut of animals subjected to PH
      compared with that in the control group of animals not subjected to PH (P <
      0.01). However, the group that received glutamine for seven days after the PPVL
      showed similar GTx activity to both the control groups not subjected to PH (P >
      0.05). At least 10 random, non-overlapping images of each histological slide with
      200 * magnification (44 pixel = 1 MUm) were captured. The sum means of all areas,
      of each group were calculated. The mean areas of eNOS staining for both of the
      control groups were similar. The PPVL group showed the largest area of staining
      for eNOS. The PPVL + G group had the second highest amount of staining, but the
      mean value was much lower than that of the PPVL group (P < 0.01). For iNOS, the
      control (SO) and control + G (SO + G) groups showed similar areas of staining.
      The PPVL group contained the largest area of iNOS staining, followed by the PPVL
      + G group; however, this area was significantly smaller than that of the group
      that underwent PH without glutamine (P < 0.01). CONCLUSION: Treatment with
      glutamine prevents gut mucosal injury after PH in rats.

PMID- 28740342
TI  - Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients
      who are non-responders to two or more treatments and its relationship with
      response to a new treatment.
AB  - AIM: To determine the number of mutations in the NS5A region of the hepatitis C
      virus (HCV) and its relationship to the response to antiviral therapy in patients
      with chronic hepatitis C genotype 1 who are non-responders to two or more
      treatments. METHODS: Sequences within HCV NS5A [PKR binding domain (PKRBD) and
      the interferon-sensitivity-determining region (ISDR)] were analysed via direct
      sequencing in a selected cohort of 72 patients, with a total of 201 treatments
      [interferon-alpha (IFN-alpha), n = 49; IFN-alpha + ribavirin (RBV), n = 75;
      pegylated (peg) IFN-alpha + RBV, n = 47; first-generation direct-acting
      antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201
      achieved a sustained virological response (SVR) and 153/201 achieved no
      virological response (NVR). RESULTS: For both regions, treatments resulting in
      SVR were associated with more baseline mutations than were treatments resulting
      in NVR (SVR vs NVR; PKRBD: 5.82 +/- 3 vs 4.86 +/- 2 mutations, P = 0.045; ISDR:
      2.65 +/- 2 vs 1.51 +/- 1.7 mutations, P = 0.005). A decrease or no change in the
      number of mutations over time between treatments in the PKRBD or ISDR, as shown
      by sequencing, was associated with patients who usually failed to respond to
      treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post
      treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with
      respect to the previous treatment were 9.21 times more likely to achieve SVR (P =
      0.001). CONCLUSION: The obtained results show that among patients who have shown
      no response to two or more antiviral treatments, the likelihood of achieving SVR
      increases with the genetic variability in the ISDR region (>= 2 mutations or
      number of substitutions from the HCV-J and HCV-1 prototype), especially when the
      viral load is greater than 600000 IU/mL.

PMID- 28740343
TI  - Distinct gut microbiota profiles in patients with primary sclerosing cholangitis
      and ulcerative colitis.
AB  - AIM: To characterize the gut bacterial microbiota of patients with primary
      sclerosing cholangitis (PSC) and ulcerative colitis (UC). METHODS: Stool samples
      were collected and relevant clinical data obtained from 106 study participants,
      43 PSC patients with (n = 32) or without (n = 11) concomitant inflammatory bowel
      disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the
      16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low
      taxonomic levels. Data were further processed in QIIME employing MaAsLin and
      LEfSe tools for analysis of the output data. RESULTS: Microbial profiles in both
      PSC and UC were characterized by low bacterial diversity and significant change
      in global microbial composition. Rothia, Enterococcus, Streptococcus,
      Veillonella, and three other genera were markedly overrepresented in PSC
      regardless of concomitant inflammatory bowel disease (IBD). Rothia, Veillonella
      and Streptococcus were tracked to the species level to identify Rothia
      mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with
      Veillonella parvula and V. dispar. PSC was further characterized by decreased
      abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus
      Phascolarctobacterium was linked to presence of colonic inflammation regardless
      of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and
      Clostridium colinum were decreased in UC along with genus Roseburia. Low levels
      of serum albumin were significantly correlated with enrichment of order
      Actinomycetales. CONCLUSION: PSC is associated with specific gut microbes
      independently of concomitant IBD and several bacterial taxa clearly distinguish
      IBD phenotypes (PSC-IBD and UC).

PMID- 28740344
TI  - Anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of
      oxidative stress in a dextran sulfate sodium-induced colitis model.
AB  - AIM: To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin
      by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced
      colitis model. METHODS: An acute colitis mouse model was induced by oral
      administration of 5% DSS in the drinking water for 7 d. In the treated group,
      rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS
      administration for 21 d. On day 21, mice were sacrificed and the colons were
      removed for macroscopic examination, histology, and Western blot analysis. In the
      in vitro study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor
      (TNF)-alpha and then treated with or without rosuvastatin (2 MUmol/L). The levels
      of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers
      were measured. RESULTS: In DSS-induced colitis mice, rosuvastatin treatment
      significantly reduced the disease activity index and histological damage score
      compared to untreated mice (P < 0.05). Rosuvastatin also attenuated the DSS
      induced increase of 8-hydroxy-2'-deoxyguanosine and NADPH oxidase-1 expression in
      colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment
      reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL
      17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and
      poly (ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin
      treatment. In vitro, rosuvastatin significantly reduced the production of ROS,
      inflammatory mediators and apoptotic markers in TNF-alpha-treated IEC-6 cells (P
      < 0.05). CONCLUSION: Rosuvastatin had the antioxidant, anti-inflammatory and anti
      apoptotic effects in DSS-induced colitis model. Therefore, it might be a
      candidate anti-inflammatory drug in patients with inflammatory bowel disease.

PMID- 28740345
TI  - miR-29a promotes hepatitis B virus replication and expression by targeting
      SMARCE1 in hepatoma carcinoma.
AB  - AIM: To investigate the functional role and underlying molecular mechanism of miR
      29a in hepatitis B virus (HBV) expression and replication. METHODS: The levels of
      miR-29a and SMARCE1 in HBV-infected HepG2.2.15 cells were measured by
      quantitative real-time PCR and western blot analysis. HBV DNA replication was
      measured by quantitative PCR and Southern blot analysis. The relative levels of
      hepatitis B surface antigen and hepatitis B e antigen were detected by enzyme
      linked immunosorbent assay. The Cell Counting Kit-8 (CCK-8) was used to detect
      the viability of HepG2.2.15 cells. The relationship between miR-29a and SMARCE1
      were identified by target prediction and luciferase reporter analysis. RESULTS:
      miR-29a promoted HBV replication and expression, while SMARCE1 repressed HBV
      replication and expression. Cell viability detection indicated that miR-29a
      transfection had no adverse effect on the host cells. Moreover, SMARCE1 was
      identified and validated to be a functional target of miR-29a. Furthermore,
      restored expression of SMARCE1 could relieve the increased HBV replication and
      expression caused by miR-29a overexpression. CONCLUSION: miR-29a promotes HBV
      replication and expression through regulating SMARCE1. As a potential regulator
      of HBV replication and expression, miR-29a could be a promising therapeutic
      target for patients with HBV infection.

PMID- 28740346
TI  - Management and outcome of hepatocellular adenoma with massive bleeding at
      presentation.
AB  - AIM: To evaluate outcome of acute management and risk of rebleeding in patients
      with massive hemorrhage due to hepatocellular adenoma (HCA). METHODS: This
      retrospective cohort study included all consecutive patients who presented to our
      hospital with massive hemorrhage (grade II or III) due to ruptured HCA and were
      admitted for observation and/or intervention between 1999-2016. The diagnosis of
      HCA was based on radiological findings from contrast-enhanced magnetic resonance
      imaging (MRI) or pathological findings from biopsy or resection of the HCA.
      Hemorrhage was diagnosed based on findings from computed tomography or MRI.
      Medical records were reviewed for demographic features, clinical presentation,
      tumor features, initial and subsequent management, short- and long-term
      complications and patient and lesion follow-up. RESULTS: All patients were female
      (n = 23). Treatment in the acute phase consisted of embolization (n = 9, 39.1%),
      conservative therapy (n = 13, 56.5%), and other intervention (n = 1, 4.3%).
      Median hemoglobin level decreased significantly more on days 0-3 in the
      intervention group than in the patients initially treated conservatively (0.9
      mmol/L vs 2.4 mmol/L respectively, P = 0.006). In total, 4 patients suffered
      severe short-term complications, which included hypovolemic shock, acute liver
      failure and abscess formation. After a median follow-up of 36 mo, tumor
      regression in non-surgically treated patients occurred with a median reduction of
      76 mm down to 25 mm. Four patients underwent secondary (elective) treatment
      (i.e., tumor resection) to address HCA size of > 5 cm and/or desire for future
      pregnancy. One case of rebleeding was documented (4.3%). None of the patients
      experienced long-term complication (mean follow-up time: 36 mo). CONCLUSION: With
      a 4.3% risk of rebleeding, secondary (elective) treatment of HCA after massive
      hemorrhage may only be considered in patients with persistent HCA > 5 cm.

PMID- 28740347
TI  - Chronic hepatitis B, nonalcoholic steatohepatitis and physical fitness of
      military males: CHIEF study.
AB  - AIM: To investigate the association of chronic hepatitis B and nonalcoholic
      steatohepatitis with physical fitness in a Taiwanese military male cohort.
      METHODS: We made a cross-sectional examination of this association using 3669
      young adult military males according to cardiorespiratory fitness and
      hospitalization events recorded in the Taiwan Armed Forces study. Cases of
      chronic hepatitis B (n = 121) were defined by personal history and positive
      detection of hepatitis B surface antigen. Cases of nonalcoholic steatohepatitis
      (n = 129) were defined by alanine transaminase level > 60 U/L, liver ultrasound
      finding of steatosis, and absence of viral hepatitis A, B or C infection. All
      other study participants were defined as unaffected (n = 3419). Physical fitness
      was evaluated by performance in 3000-m run, 2-min sit-ups, and 2-min push-ups
      exercises, with all the procedures standardized by a computerized scoring system.
      Multiple linear regression analysis was used to determine the relationship.
      RESULTS: Chronic hepatitis B negatively correlated with 2-min push-up numbers
      (beta = -2.49, P = 0.019) after adjusting for age, service specialty, body mass
      index, systolic and diastolic blood pressures, current cigarette smoking, alcohol
      intake status, serum hemoglobin, and average weekly exercise times. Nonalcoholic
      steatohepatitis was borderline positively correlated with 3000-m running time
      (beta = 11.96, P = 0.084) and negatively correlated with 2-min sit-up numbers
      (beta = -1.47, P = 0.040). CONCLUSION: Chronic hepatitis B viral infection and
      nonalcoholic steatohepatitis affects different physical performances in young
      adult military males, and future study should determine the underlying mechanism.

PMID- 28740348
TI  - Comparison of short- and long-term outcomes of laparoscopic vs open resection for
      gastric gastrointestinal stromal tumors.
AB  - AIM: To compare the short- and long-term outcomes of laparoscopic (LR) vs open
      resection (OR) for gastric gastrointestinal stromal tumors (gGISTs). METHODS: In
      total, 301 consecutive patients undergoing LR or OR for pathologically confirmed
      gGISTs from 2005 to 2014 were enrolled in this retrospective study. After
      exclusion of 77 patients, 224 eligible patients were enrolled (122 undergoing LR
      and 102 undergoing OR). The demographic, clinicopathologic, and survival data of
      all patients were collected. The intraoperative, postoperative, and long-term
      oncologic outcomes were compared between the LR and OR groups following the
      propensity score matching to balance the measured covariates between the two
      groups. RESULTS: After 1:1 propensity score matching for the set of covariates
      including age, sex, body mass index, American Society of Anesthesiology score,
      tumor location, tumor size, surgical procedures, mitotic count, and risk
      stratification, 80 patients in each group were included in the final analysis.
      The baseline parameters of the two groups were comparable after matching. The LR
      group was significantly superior to the OR group with respect to the operative
      time, intraoperative blood loss, postoperative first flatus, time to oral intake,
      and postoperative hospital stay (P < 0.05). No differences in perioperative blood
      transfusion or the incidence of postoperative complications were observed between
      the two groups (P > 0.05). No significant difference was found in postoperative
      adjuvant therapy (P = 0.587). The mean follow-up time was 35.30 +/- 26.02 (range,
      4-102) mo in the LR group and 40.99 +/- 25.07 (range, 4-122) mo in the OR group
      with no significant difference (P = 0.161). Survival analysis showed no
      significant difference in the disease-free survival time or overall survival time
      between the two groups (P > 0.05). CONCLUSION: Laparoscopic surgery for gGISTs is
      superior to open surgery with respect to intraoperative parameters and
      postoperative outcomes without compromising long-term oncological outcomes.

PMID- 28740349
TI  - Functional lipidomics in patients on home parenteral nutrition: Effect of lipid
      emulsions.
AB  - AIM: To investigate the fatty acid-based functional lipidomics of patients on
      long-term home parenteral nutrition receiving different intravenous lipid
      emulsions. METHODS: A cross-sectional comparative study was carried out on 3
      groups of adults on home parenteral nutrition (HPN), receiving an HPN admixture
      containing an olive-soybean oil-based intravenous lipid emulsion (IVLE) (OO-IVLE;
      n = 15), a soybean- medium-chain triacylglycerol-olive-fish oil-based IVLE (SMOF
      IVLE; n = 8) or HPN without IVLE (No-IVLE; n = 8) and 42 healthy controls (HCs).
      The inclusion criteria were: duration of HPN >= 3 mo, current HPN admixtures >= 2
      mo and HPN infusions >= 2/wk. Blood samples were drawn 4-6 h after the
      discontinuation of the overnight HPN infusion. The functional lipidomics panel
      included: the red blood cell (RBC) fatty acid (FA) profile, molecular biomarkers
      [membrane fluidity: saturated/monounsaturated FA ratio = saturated fatty acid
      (SFA)/monounsaturated fatty acid (MUFA) index; inflammatory risk: n-6/n-3
      polyunsaturated fatty acid (PUFA) ratio = n-6/n-3 index; cardiovascular risk: sum
      of n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) = n-3 index;
      free radical stress: sum of FA trans isomers = %trans index] and FA pathway
      enzyme activity estimate (delta-9-desaturase = D9D; delta-6-desaturase = D6D;
      delta-5-desaturase = D5D; elongase = ELO). Statistics were carried out using
      nonparametric tests. The amount of each FA was calculated as a percentage of the
      total FA content (relative%). RESULTS: In the OO-IVLE group, the percentage of
      oleic acid in the RBCs was positively correlated with the weekly load of OO-IVLE
      (r = 0.540, P = 0.043). In the SMOF-IVLE cohort, the RBC membrane EPA and DHA
      were positively correlated with the daily amount of SMOF-IVLE (r = 0.751, P =
      0.044) and the number of HPN infusions per week (r = 0.753; P = 0.046),
      respectively. The SMOF-IVLE group showed the highest EPA and DHA and the lowest
      arachidonic acid percentages (P < 0.001). The RBC membrane linoleic acid content
      was lower, and oleic and vaccenic acids were higher in all the HPN groups in
      comparison to the HCs. Vaccenic acid was positively correlated with the weekly
      HPN load of glucose in both the OO-IVLE (r = 0.716; P = 0.007) and the SMOF-IVLE
      (r = 0.732; P = 0.053) groups. The estimated activity of D9D was higher in all
      the HPN groups than in the HCs (P < 0.001). The estimated activity of D5D was
      lower in the SMOF-IVLE group than in the HCs (P = 0.013). The SFA/MUFA ratio was
      lower in all the HPN groups than in the HCs (P < 0.001). The n-6/n-3 index was
      lower and the n-3 index was higher in the SMOF-IVLE group in comparison to the
      HCs and to the other HPN groups (P < 0.001). The %trans index did not differ
      among the four groups. CONCLUSION: The FA profile of IVLEs significantly
      influenced the cell membrane functional lipidomics. The amount of glucose in the
      HPN may play a relevant role, mediated by the insulin regulation of the FA
      pathway enzyme activities.

PMID- 28740350
TI  - Cryptogenic multifocal ulcerous stenosing enteritis: Radiologic features and
      clinical behavior.
AB  - AIM: To investigate the characteristic radiologic findings of cryptogenic
      multifocal ulcerous stenosing enteritis (CMUSE) which can be differentiated from
      other similar bowel disease and to assess their clinical behavior. METHODS:
      Twenty pathologically and clinically confirmed CMUSE patients (males:females =
      8:12; mean age: 40.4 years) between March 2002 and August 2015 from seven
      academic centers in South Korea were retrospectively reviewed. We evaluated small
      bowel series (SBS; n = 25), computed tomography (CT) enterography (n = 21),
      magnetic resonance (MR) enterography (n = 2), and abdominopelvic CT (n = 18)
      images, focusing on enteric and perienteric manifestations. Any change in
      radiologic features during follow-up period was recorded. We evaluated clinical
      data including presenting symptoms, laboratory finding and presence of relapse
      from electronic medical records. Histopathologic findings were also evaluated.
      RESULTS: The main symptoms were abdominal pain (n = 12) and anemia (n = 10). All
      patients showed small bowel strictures (n = 52, mean: 2.6 per patient) on initial
      CT/MR, located in the ileum (n = 47) or jejunum (n = 5). Strictures showed short
      length (mean: 10.44 mm) and circumferential bowel wall thickening (mean: 5.56 mm)
      with layered enhancement (n = 48) that were also noted on initial SBS (n = 36)
      with shallow ulcers (n = 10). Some ulcerative lesions or wall thickening
      progressed into strictures on follow-up SBS/CT, and some strictures revealed
      recurrent ulceration on follow-up SBS. There were no penetrating disease features
      like fistula or abscess and no gastrointestinal tract involvement except the
      small bowel. Nine patients experienced disease recurrence (median relapse-free
      period: 32 mo) even post-operatively. Histopathologic features of surgically
      resected specimens were characterized as multiple superficial ulcerations
      confined to mucosa or submucosa and multiple strictures. CONCLUSION: Under
      characteristic radiologic findings with multiple short-segmental strictures
      and/or shallow ulcers of the small intestine, CMUSE should be considered when
      assessing patients with recurrent abdominal pain and anemia.

PMID- 28740351
TI  - Partners of patients with ulcerative colitis exhibit a biologically relevant
      dysbiosis in fecal microbial metacommunities.
AB  - AIM: To investigate alterations in the fecal microbiome using 16S rRNA amplicon
      sequencing in couples in the same cohabitation environment. METHODS: Fecal
      samples were collected from eight ulcerative colitis (UC) patients and their
      healthy partners at Lishui People's Hospital, Zhejiang Province, China. DNA was
      extracted and the variable regions V3 and V4 of the 16S rRNA genes were PCR
      amplified using a two-step protocol. Clear reads were clustered into operational
      taxonomic units (OTUs) at the 97% sequence similarity level using UCLUST v1.2.22.
      The Wilcoxon rank-sum test (R v3.1.2) was used to compare inter-individual
      differences. Differences with a P value < 0.05 were considered statistically
      significant. RESULTS: Fecal microbial communities were more similar among UC
      patients than their healthy partners (P = 0.024). UC individuals had a lower
      relative abundance of bacteria belonging to the Firmicutes, especially Blautia,
      Clostridium, Coprococcus and Roseburia (P < 0.05). Microbiota dysbiosis was
      detected in UC patients and their healthy partners. Relevant genera included
      Akkermansiam, Bacteroides, Escherichia, Lactobacillales, Klebsiella and
      Parabacteroides. The enriched pathways in fecal samples of UC patients were
      related to lipid and nucleotide metabolism. Additionally, the pathways involved
      in membrane transport and metabolism of cofactors and vitamins were more abundant
      in the healthy partners. CONCLUSION: Our results suggested that the microbial
      composition might be affected in healthy partners cohabiting with UC patients,
      especially in terms of microbiota dysbiosis.

PMID- 28740352
TI  - Long-term irritable bowel syndrome symptom control with reintroduction of
      selected FODMAPs.
AB  - AIM: To investigate the long-term effect of dietary education on a low
      fermentable oligosaccharide, disaccharide and polyol (FODMAP) diet on irritable
      bowel syndrome (IBS) symptoms and quality of life (QoL). METHODS: Participants
      with IBS (Rome III) were randomized to two groups. Group I commenced a low FODMAP
      diet at baseline. At three months, group II, so far a comparator group, crossed
      over to a low FODMAP diet while group I started re-challenging foods. All
      patients completed the IBS SSS (IBS symptom severity scoring system, 0-500 points
      increasing with severity), IBS QoL questionnaire (0-100 increasing with QoL), a
      FODMAP specific food frequency questionnaire and provided a stool sample at
      baseline, three and six months for microbiome analysis. RESULTS: Fifty
      participants were enrolled into group I (n = 23) or group II (n = 27).
      Participants in both groups were similar in baseline values but with more men in
      group I. There was a significantly lower IBS SSS (275.6 +/- 63.6 to 128.8 +/-
      82.5 vs 246.8 +/- 71.1 to 203.6 +/- 70.1) (P < 0.0002) and increased QoL (68.5 +/
      18.0 to 83 +/- 13.4 vs 72.9 +/- 12.8 to 73.3 +/- 14.4) (P < 0.0001) in group I
      vs group II at 3 mo. The reduced IBS SSS was sustained at 6 mo in group I (160 +/
      102) and replicated in group II (124 +/- 76). Fiber intake decreased on the low
      FODMAP diet (33 +/- 17 g/d to 21 +/- 8 g/d) (P < 0.01) and after re-introducing
      FODMAP containing foods increased again to 27 +/- 9 g/d. There was no change seen
      in the intestinal microbiome when participants adopted a low FODMAP diet.
      CONCLUSION: This study demonstrated that a reduction in FODMAPs improves symptoms
      in IBS and this improvement can be maintained while reintroducing FODMAPs.

PMID- 28740353
TI  - Anti-apoptotic effect of banhasasim-tang on chronic acid reflux esophagitis.
AB  - AIM: To evaluate the anti-apoptotic effect of banhasasim-tang (BHSST) on chronic
      acid reflux esophagitis (CARE) using a rat model. METHODS: A surgically-induced
      CARE model was established in Sprague-Dawley rats. The modeled rats were divided
      into a treatment group or untreated group, and given BHSST (1 g/kg body weight
      per day) or water, respectively, for 15 consecutive days (n = 7 each group).
      Changes in expression of proteins related to nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase and apoptosis were assessed by western blotting.
      Changes in esophageal pathology were analyzed by gross and histological
      examinations. RESULTS: The CARE exposure modeled rats showed increased levels of
      the NADPH oxidase subunit, NOX4 and p47phox in the esophagus. The BHSST treatment
      completely resolved these CARE-related increases. The CARE rats also showed
      markers of cytokine stress, including elevated levels of TNF-alpha and reactive
      oxygen species as well as of the consequent increase in JNK activation, and
      subsequent decrease in pro-survival gene expression, such as of Bcl-2. BHSST
      treatment resolved the CARE-related changes. BHSST also exerted an anti-apoptotic
      effect, as evidenced by altered expression of the apoptosis-related genes for
      bax, cytochrome c, and caspase 3. Finally, the BHSST treatment markedly
      ameliorated the CARE-related esophageal mucosal ulcerations. CONCLUSION: In the
      rat model of CARE, BHSST can suppress development of esophageal mucosal
      ulceration via regulation of reactive oxygen species-dependent apoptosis.

PMID- 28740354
TI  - Nosocomial spontaneous bacterial peritonitis antibiotic treatment in the era of
      multi-drug resistance pathogens: A systematic review.
AB  - AIM: To systematically review literature upon aetiology of nosocomial spontaneous
      bacterial peritonitis (N-SBP) given the rising importance of multidrug-resistant
      (MDR) bacteria. METHODS: A literature search was performed on MEDLINE and Google
      Scholar databases from 2000 to 15th of November 2016, using the following search
      strategy: "spontaneous" AND "peritonitis". RESULTS: The initial search through
      electronic databases retrieved 2556 records. After removing duplicates, 1958
      records remained. One thousand seven hundred and thirty-five of them were
      excluded on the basis of the screening of titles and abstract, and the ensuing
      number of remaining articles was 223. Of these records, after careful evaluation,
      only 9 were included in the qualitative analysis. The overall proportion of MDR
      bacteria turned out to be from 22% to 73% of cases across the studies.
      CONCLUSION: N-SBP is caused, in a remarkable proportion, by MDR pathogens. This
      should prompt a careful re-assessment of guidelines addressing the treatment of
      this clinical entity.

PMID- 28740355
TI  - Insights into Cruciform Sample Design.
AB  - Four different cruciform sample designs, based on the work of Abu-Farha et al.,
      were studied in this paper. Key features of this design are a recessed pocket
      with fillet and re-entrant corners. These samples were shown via digital image
      correlation to achieve widely differing strain values inside and outside the
      pocket. From the results of these tests, there are two competing failure
      mechanisms in the sample. The pocket region is affected by stress concentrations
      caused by the fillet, and re-entrant notches lead to strain limited constraints
      similar to diffuse and localized necks in uniaxial samples. Balancing these two
      constraints determines the success or premature failure of the sample.

PMID- 28740356
TI  - Social Interpretation Bias in Children and Adolescents with Anxiety Disorders:
      Psychometric Examination of the Self-report of Ambiguous Social Situations for
      Youth (SASSY) Scale.
AB  - BACKGROUND: Anxiety disorders are among the most common mental health problems in
      youth, and faulty interpretation bias has been positively linked to anxiety
      severity, even within anxiety-disordered youth. Quick, reliable assessment of
      interpretation bias may be useful in identifying youth with certain types of
      anxiety or assessing changes on cognitive bias during intervention. OBJECTIVE:
      This study examined the factor structure, reliability, and validity of the Self
      report of Ambiguous Social Situations for Youth (SASSY) scale, a self-report
      measure developed to assess interpretation bias in youth. METHODS: Participants
      (N=488, age 7 to 17) met diagnostic criteria for Social Phobia, Generalized
      Anxiety Disorder, and/or Separation Anxiety Disorder. An exploratory factor
      analysis was performed on baseline data from youth participating in a large
      randomized clinical trial. RESULTS: Exploratory factor analysis yielded two
      factors (Accusation/Blame, Social Rejection). The SASSY full scale and Social
      Rejection factor demonstrated adequate internal consistency, convergent validity
      with social anxiety, and discriminant validity as evidenced by non-significant
      correlations with measures of non-social anxiety. Further, the SASSY Social
      Rejection factor accurately distinguished children and adolescents with Social
      Phobia from those with other anxiety disorders, supporting its criterion
      validity, and revealed sensitivity to changes with treatment. Given the relevance
      to youth with social phobia, pre- and post-intervention data were examined for
      youth social phobia to test sensitivity to treatment effects; results suggested
      that SASSY scores reduced for treatment responders. CONCLUSIONS: Findings suggest
      the potential utility of the SASSY Social Rejection factor as a quick, reliable,
      and efficient way of assessing interpretation bias in anxious youth, particularly
      as related to social concerns, in research and clinical settings.

PMID- 28740357
TI  - Diffusion of multiwall carbon nanotubes (MWCNTs) through a high density
      polyethylene (HDPE) geomembrane.
AB  - The new applications for carbon nanotubes (CNTs) in various fields and
      consequently their greater production volume have increased their potential
      release to the environment. Landfills are one of the major locations where carbon
      nanotubes are expected to be disposed and it is important to ensure that they can
      limit the release of CNTs. Diffusion of multiwall carbon nanotubes (MWCNTs)
      dispersed in an aqueous media through a high-density polyethylene (HDPE)
      geomembrane (as a part of the landfill barrier system) was examined. Based on the
      laboratory tests, the permeation coefficient was estimated to be less than 5.1*10
      15 m2/s. The potential performance of a HDPE geomembrane and geosynthetic clay
      liner (GCL) as parts of a composite liner in containing MWCNTs was modelled for
      six different scenarios. The results suggest that the low value of permeation
      coefficient of an HDPE geomembrane makes it an effective diffusive barrier for
      MWCNTs and by keeping the geomembrane defects to minimum during the construction
      (e.g., number of holes and length of wrinkles) a composite liner commonly used in
      municipal solid waste landfills will effectively contain MWCNTs.

PMID- 28740358
TI  - Compression of Morbidity and Mortality: New Perspectives.
AB  - Compression of morbidity is a reduction over time in the total lifetime days of
      chronic disability, reflecting a balance between (1) morbidity incidence rates
      and (2) case-continuance rates-generated by case-fatality and case-recovery
      rates. Chronic disability includes limitations in activities of daily living and
      cognitive impairment, which can be covered by long-term care insurance. Morbidity
      improvement can lead to a compression of morbidity if the reductions in age
      specific prevalence rates are sufficiently large to overcome the increases in
      lifetime disability due to concurrent mortality improvements and progressively
      higher disability prevalence rates with increasing age. Compression of mortality
      is a reduction over time in the variance of age at death. Such reductions are
      generally accompanied by increases in the mean age at death; otherwise, for the
      variances to decrease, the death rates above the mean age at death would need to
      increase, and this has rarely been the case. Mortality improvement is a reduction
      over time in the age-specific death rates and a corresponding increase in the
      cumulative survival probabilities and age-specific residual life expectancies.
      Mortality improvement does not necessarily imply concurrent compression of
      mortality. This paper reviews these concepts, describes how they are related,
      shows how they apply to changes in mortality over the past century and to changes
      in morbidity over the past 30 years, and discusses their implications for future
      changes in the United States. The major findings of the empirical analyses are
      the substantial slowdowns in the degree of mortality compression over the past
      half century and the unexpectedly large degree of morbidity compression that
      occurred over the morbidity/disability study period 1984-2004; evidence from
      other published sources suggests that morbidity compression may be continuing.

PMID- 28740359
TI  - A new lens for observing fundus with a noncontact wide-angle viewing system.
AB  - Drying of the cornea during surgery, which causes poor visibility of the fundus,
      is one of the most serious problems when using a noncontact-type wide-angle
      viewing system. This study used a newly commercialized lens for observing the
      fundus with a noncontact wide-angle viewing system. The lens used has a very thin
      meniscus made of polymethyl methacrylate and a large outer diameter. Following
      the application of viscoelastic material, the lens can be put on the cornea
      without using a contact lens fixation ring. The larger diameter and lightweight
      characteristics of the new lens contributed to the overall stabilization. The
      smooth surface of this lens was able to achieve an intraoperative view of good
      quality not only during vitrectomy but also during scleral buckling procedures.

PMID- 28740360
TI  - Visual processing in patients with age-related macular degeneration performing a
      face detection test.
AB  - PURPOSE: People with age-related macular degeneration (AMD) have difficulties in
      familiar face recognition and facial expression discrimination. Our aim was to
      evaluate the visual processing of faces in AMD patients and whether this would be
      improved by anti-vascular endothelial growth factor therapy. This was a
      prospective interventional cohort study. PATIENTS: Twelve patients with monocular
      wet AMD and 6 control subjects were recruited. Face detection processes were
      studied using cortical event-related potentials (ERPs). Patients received 3
      bevacizumab intravitreal injections to the single affected eye. At baseline and 4
      6 weeks after the last injection, clinical presentation and ERPs of the face task
      were evaluated. Face pictures were shown as targets (16.7%) among standard
      pictures of pixelated faces in an oddball-type paradigm. RESULTS: Face pictures
      elicited well-defined electrical components in occipital and parieto-occipital
      cortical areas at baseline and after treatment. The face-specific N170 component
      was evident in all subjects with longer peak latency in patients than in controls
      (170+/-13 vs 155+/-14, P=0.032). Unexpectedly, an early component reflecting
      unintentional prediction of perceiving a face, that is, deviance-related
      negativity, was present in patients and controls. Visual acuity of the affected
      eye seemed improved in patients from logarithm of the minimum angle of resolution
      0.71 (+/-0.33) to 0.52 (+/-0.39) by 119 (+/-23) days without accompanying
      significant change in face-specific ERPs. CONCLUSIONS: Monocular wet AMD
      distinctly influenced face-specific brain electrophysiological components.
      However, the anti-vascular endothelial growth factor treatment did not improve
      the binocular face detection ability. The EudraCT number of this study is 2012
      000765-20.

PMID- 28740361
TI  - Matched population comparison of visual outcomes and patient satisfaction between
      3 modalities for the correction of low to moderate myopic astigmatism.
AB  - PURPOSE: To compare toric implantable collamer lens (T-ICL), femto-LASIK, and
      ReLEx SMILE for the treatment of low to moderate myopic astigmatism in terms of
      long-term visual and refractive outcomes and predictability of astigmatic
      correction. MATERIALS AND METHODS: The study included 30 eyes from 30 patients
      between the age groups of 21 and 40 years, undergoing bilateral surgery with any
      of the three procedures - T-ICL, femto-LASIK, or ReLEx SMILE - for correction of
      myopic astigmatism within the range of -3 to -8 D spherical equivalent (SE), with
      a minimum astigmatism of -0.75 D. Patients were followed up at day 1, 1 month, 6
      months, and 1 year. RESULTS: At 1 year, the mean cylinder reduced to -0.21+/
      0.28, -0.17+/-0.36, and -0.22+/-0.28 D in the T-ICL, femto-LASIK, and ReLEx SMILE
      group, respectively. The predictability of astigmatism correction was comparable,
      with no statistically significant difference between the 3 groups (P>0.05). A
      total of 97% of eyes in ReLEx SMILE achieved a uncorrected distance visual acuity
      of 20/20 or better, compared to T-ICL (93%) and FS-LASIK (90%). However, gain in
      lines of corrected distant visual acuity (CDVA) was maximum in T-ICL group (60%).
      Four eyes in the femto-LASIK group had loss of CDVA by one line. Three eyes
      required exchange due to high vault and rotation of the T-ICL, which did not
      affect the final outcome. CONCLUSION: All 3 modalities were effective for myopic
      astigmatism at the end of 1 year. Quality of vision and patient satisfaction with
      T-ICL and ReLEx SMILE were similar and better than FS-LASIK. However, slight
      chances of postoperative rotation and exchange exist with T-ICL, which warrant
      thorough preoperative planning.

PMID- 28740362
TI  - Scleral wound healing with cross-link technique using riboflavin and ultraviolet
      A on rabbit eyes.
AB  - PURPOSE: The aim of study was to evaluate the cross-link using riboflavin and
      ultraviolet A (UVA) for improving scleral wound healing. MATERIALS AND METHODS:
      This was an experimental study involving four New Zealand rabbits (eight eyes).
      Therapy procedure was chosen for the right eye and control procedure for the left
      one. UVA irradiation of 365 nm with a surface irradiance of 3 mW/cm2 and a
      photosensitizer of riboflavin drops were applied for 30 minutes on the right eye
      at 2 mm from the limbus. Sclerotomy incision was performed at 2 mm from the
      limbus in both right (on the cross-link-treated area) and left eye. Then, 30 days
      after surgery, a morphological analysis and histological staining with
      hematoxylin-eosin and picrosirius red were performed, and the sclerotomy
      cicatrization of right and left eyes was compared. The variables investigated
      were as follows: sclerotomy incision pictures and measurements were made using
      the ImageJ Software. Scleral thickness was measured (employing the anterior
      optical coherence tomography and the digital caliper). Collagen fiber density
      stained with picrosirius red staining was measured using the Image Pro Plus
      software. RESULTS: The morphological analysis showed that in all samples, the
      right eye presented sclerotomy closure, and in two eyes, among them, there were
      no visible edges of the sclerotomies incision. The left eye presented sclerotomy
      closure and incision edges. The Image Pro demonstrated a higher density of
      collagen fibers in the right eye when compared to the one. The statistical
      analysis was significant when compared to the collagen fiber density in the
      treated eyes with the control eyes. CONCLUSION: The cross-link procedure resulted
      in a better sclerotomy wound healing.

PMID- 28740363
TI  - Synthesis and antimicrobial activity of chiral quaternary N-spiro ammonium
      bromides with 3',4'-dihydro-1'H-spiro[isoindoline-2,2'-isoquinoline] skeleton.
AB  - A new class of highly functionalized tetrahydroisoquinolines with a quaternary
      carbon stereocenter was synthesized starting from an easily accessible L-tartaric
      acid. Nine strains of bacteria (Staphylococcus aureus, Streptococcus pyogenes,
      Streptococcus mutans, Streptococcus salivarius, Bacillus subtilis, Enterococcus
      faecalis, Moraxella catarrhalis, Escherichia coli, Campylobacter jejuni) were
      used for the determination of minimal inhibitory concentration (MIC) and minimal
      bactericidal concentration (MBC) of synthesized compounds. The influence of
      analyzed compounds on viability and induction of apoptosis in human skin
      fibroblasts was determined. A majority of the synthesized compounds showed the
      strongest antibacterial properties toward some gram-negative bacteria (M.
      catarrhalis and C. jejuni) with a high level of selectivity. High antibacterial
      compounds have bactericidal activity ratio MBC/MIC <=4. Our studies also proved
      that the novel compounds do not possess cytotoxic and proapoptotic potential in
      normal cells.

PMID- 28740364
TI  - Development of highly potent melanogenesis inhibitor by in vitro, in vivo and
      computational studies.
AB  - The present work describes the synthesis of few hydroxylated amide derivatives as
      melanogenesis inhibitors. In vitro, in vivo and computational studies proved that
      compound 6d is a highly potent melanogenesis inhibitor compared to standard kojic
      acid. The title amides 4a-e and 6a-e were synthesized following simple reaction
      routes with excellent yields. Most of the synthesized compounds exhibited good
      mushroom tyrosinase inhibitory activity, but compound 6d showed excellent
      activity (IC50 0.15 uM) compared to standard kojic acid (IC50 16.69 uM).
      Lineweaver-Burk plots were used for the determination of kinetic mechanism, and
      it was found that compounds 4c and 6d showed non-competitive inhibition while 6a
      and 6b showed mixed-type inhibition. The kinetic mechanism further revealed that
      compound 6d formed irreversible complex with the target enzyme tyrosinase. The Ki
      values determined for compounds 4c, 6a, 6b and 6d are 0.188, 0.84, 2.20 and 0.217
      uM respectively. Results of human tyrosinase inhibitory activity in A375 human
      melanoma cells showed that compound 6d exhibited 91.9% inhibi-tory activity at a
      concentration of 50 ug/mL. In vivo cytotoxicity evaluation of compound 6d in
      zebrafish embryos showed that it is non-toxic to zebrafish. Melanin
      depigmentation assay performed in zebrafish indicated that compound 6d possessed
      greater potential in decreasing melanin contents compared to kojic acid at the
      same concentration. Computational studies also supported the wet lab findings as
      compound 6d showed a highest binding affinity with the target protein (PDBID:
      2Y9X) with a binding energy value of -7.90 kcal/mol. Molecular dynamic simulation
      studies also proved that amide 6d formed the most stable complex with tyrosinase.
      Based upon our in vitro, in vivo and computational studies, we propose that
      compound 6d is a promising candidate for the development of safe cosmetic agent.

PMID- 28740366
TI  - The mediatory role of medication adherence in improving patients' medication
      experience through patient-physician communication among older hypertensive
      patients.
AB  - BACKGROUND: Understanding how patient-physician communication affects patients'
      medication experience would help hypertensive patients maintain their regular
      long-term medication therapy. This study aimed to examine whether patient
      physician communication (information and interpersonal treatment) affects
      patients' medication experience directly or indirectly through changing
      medication adherence for each of the two communication domains. METHODS: A self
      administered cross-sectional survey was conducted for older patients who had
      visited a community senior center as a member. Two communication domains were
      assessed using two subscales of the Primary Care Assessment Survey. Medication
      adherence and experience were measured using the Morisky Medication Adherence
      Scale and a five-point Likert scale, respectively. Mediatory effects were
      assessed via Baron and Kenny's procedure and a Sobel test. RESULTS: Patient
      physician communication had a positive prediction on patients' medication
      experience (beta=0.25, P=0.03), and this was fully mediated by medication
      adherence (z=3.62, P<0.001). Of the two components of patient-physician
      communication, only informative communication showed a mediatory effect (z=2.21,
      P=0.03). CONCLUSION: Patient-physician communication, specifically informative
      communication, had the potential to improve patients' medication experience via
      changes in medication adherence. This finding can inform health care stakeholders
      of the mediatory role of medication adherence in ensuring favorable medication
      experience for older hypertensive patients by fostering informative patient
      physician communication.

PMID- 28740367
TI  - "Open mesh" or "strictly selected population" recruitment? The experience of the
      randomized controlled MeMeMe trial.
AB  - Among randomized controlled trials (RCTs), trials for primary prevention require
      large samples and long follow-up to obtain a high-quality outcome; therefore the
      recruitment process and the drop-out rates largely dictate the adequacy of the
      results. We are conducting a Phase III trial on persons with metabolic syndrome
      to test the hypothesis that comprehensive lifestyle changes and/or metformin
      treatment prevents age-related chronic diseases (the MeMeMe trial, EudraCT
      number: 2012-005427-32, also registered on ClinicalTrials.gov [NCT02960711]).
      Here, we briefly analyze and discuss the reasons which may lead to participants
      dropping out from trials. In our experience, participants may back out of a trial
      for different reasons. Drug-induced side effects are certainly the most
      compelling reason. But what are the other reasons, relating to the participants'
      perception of the progress of the trial which led them to withdraw after
      randomization? What about the time-dependent drop-out rate in primary prevention
      trials? The primary outcome of this analysis is the point of drop-out from trial,
      defined as the time from the randomization date to the withdrawal date. Survival
      functions were non-parametrically estimated using the product-limit estimator.
      The curves were statistically compared using the log-rank test (P=0.64, not
      significant). Researchers involved in primary prevention RCTs seem to have to
      deal with the paradox of the proverbial "short blanket syndrome". Recruiting only
      highly motivated candidates might be useful for the smooth progress of the trial
      but it may lead to a very low enrollment rate. On the other hand, what about
      enrolling all the eligible subjects without considering their motivation? This
      might boost the enrollment rate, but it can lead to biased results on account of
      large proportions of drop-outs. Our experience suggests that participants do not
      change their mind depending on the allocation group (intervention or control).
      There is no single answer to sort out the short blanket syndrome.

PMID- 28740365
TI  - Spotlight on ceritinib in the treatment of ALK+ NSCLC: design, development and
      place in therapy.
AB  - The identification of echinoderm microtubule-associated protein-like 4 (EML4) and
      anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer
      (NSCLC) has radically changed the treatment of a subset of patients harboring
      this oncogenic driver. Crizotinib was the first ALK tyrosine kinase inhibitor to
      receive fast approval and is currently indicated as the first-line therapy for
      advanced, ALK-positive NSCLC patients. However, despite crizotinib's efficacy,
      patients almost invariably progress, with the central nervous system being one of
      the most common sites of relapse. Different mechanisms of acquired resistance
      have been identified, including secondary ALK mutations, ALK copy number
      alterations and activation of bypass tracks. Different highly potent and brain
      penetrant next-generation ALK inhibitors have been developed and tested in NSCLC
      patients with ALK rearrangements. Ceritinib, a structurally distinct and
      selective ALK inhibitor, showed 20 times higher potency than crizotinib in
      inhibiting ALK and had activity against the most common crizotinib-resistant
      mutations, including L1196M and G1269A, in preclinical models. In Phase I and II
      studies, ceritinib demonstrated pronounced activity in both crizotinib-naive and
      crizotinib-refractory patients, with responses observed regardless of the
      presence of ALK resistance mutations. Ceritinib was the first ALK inhibitor to be
      approved for the treatment of crizotinib-refractory, ALK-rearranged NSCLC, and
      recent results from a Phase III study have demonstrated superior efficacy
      compared to standard chemotherapy in the first- and second-line setting. We
      provide an extensive overview of ceritinib from the design of the compound
      through preclinical data until efficacy and toxicity results from Phase I-III
      clinical studies. We review the molecular alterations associated with resistance
      to ceritinib and highlight the importance of obtaining tumor biopsy at
      progression to tailor therapy based upon the underlying resistance mechanism. We
      finally provide an outlook on novel rational therapeutic combinations.

PMID- 28740368
TI  - Impact of adherence to biological agents on health care resource utilization for
      patients over the age of 65 years with rheumatoid arthritis.
AB  - OBJECTIVE: Poor adherence to therapy increases the patient and societal burden
      and complexity of chronic diseases such as rheumatoid arthritis (RA). In the past
      15 years, biologic disease-modifying anti-rheumatic drugs (DMARDs) have
      revolutionized the treatment of RA. However, little data are available on the
      impact of adherence to biologics on health care resources. The objective of the
      study was to determine the long-term health care resource utilization patterns of
      RA patients who were adherent to biologic DMARD therapy compared to RA patients
      who were non-adherent to biologic DMARD therapy in an Ontario population and to
      determine factors influencing adherence. METHODS: Patients were identified from
      the Ontario RA Database that contains all RA patients in Ontario, Canada,
      identified since 1991. The study population included RA patients, aged 65+ years,
      with a prescription for a biologic DMARD between 2003 and 2013. Exclusion
      criteria included diagnosis of inflammatory bowel disease, psoriatic arthritis or
      psoriasis in the 5 years prior to the index date and discontinuation of biologic
      DMARD, defined as no subsequent prescription during the 12 months after the index
      date. Adherence was defined as a medication possession ratio of >=0.8 measured as
      the proportion of days for which a patient had biologic treatment(s) over a
      defined follow-up period. Adherent patients were matched to non-adherent patients
      by propensity score matching. RESULTS: A total of 4,666 RA patients were
      identified, of whom 2,749 were deemed adherent and 1,917 non-adherent. The age
      (standard deviation) was 69.9 (5.46) years and 75% were female. Relative rates
      for resource use (physician visits, emergency visits, hospitalization, home care
      and rehabilitation) for the matched cohort were significantly lower (P?0.0001) in
      adherent patients. Non-adherent patients' use of oral prednisone (67%) was
      significantly higher (P?0.001) than that of the adherent cohort (56%).
      CONCLUSION: RA patients adherent to biologic therapy have lower health care
      resource use and lower steroid use compared to non-adherent patients.

PMID- 28740369
TI  - Spotlight on brimonidine topical gel 0.33% for facial erythema of rosacea:
      safety, efficacy, and patient acceptability.
AB  - BACKGROUND: Brimonidine tartrate is a highly selective alpha 2 agonist that
      induces direct vasoconstriction of small arteries and veins, thereby reducing
      vasodilation and edema. OBJECTIVE: To review the current literature regarding the
      safety, efficacy, and patient acceptability of brimonidine 0.33% gel. METHODS: A
      PubMed search was performed using the terms brimonidine 0.33% gel, rosacea,
      safety, efficacy, and acceptability. Peer-reviewed clinical trials and case
      reports from 2012 to 2016 were screened for inclusion of safety, efficacy, and/or
      patient acceptability data. RESULTS: Brimonidine topical gel 0.33% is associated
      with mild, transient skin-related adverse reactions. Efficacy may be achieved
      within 30 minutes of administration with maximal reductions in erythema 3-6 hours
      after administration. Patient satisfaction with use of brimonidine topical gel is
      superior to vehicle gel for facial appearance, treatment effect, facial redness,
      and daily control of facial redness. LIMITATIONS: Studies were typically limited
      to 1-year follow-up. Only one study has examined the use of brimonidine topical
      gel in combination with other rosacea and acne medications. DISCUSSION:
      Brimonidine topical gel 0.33% is a safe, effective, and patient-accepted
      treatment for facial erythema of rosacea.

PMID- 28740370
TI  - Kidney function and cognitive decline in an oldest-old Chinese population.
AB  - BACKGROUND: Early-stage chronic kidney disease has been suggested to be
      correlated with cognitive decline, but the association has rarely been explored
      in the oldest old. SUBJECTS AND METHODS: This prospective study included 284
      Chinese participants aged 80 years or older with serum creatinine levels <150
      umol/L. The median follow-up time was 3.3 years, and 247 (87.0%) participants
      provided valid data at their last visit. Kidney function was evaluated by
      measuring the estimated glomerular filtration rate (eGFR) at baseline, and
      cognitive function was evaluated using the Mini-Mental State Examination (MMSE)
      at both baseline and annual visits. A reliable decrease in the MMSE score over
      the follow-up period was observed based on a Reliable Change Index of 1.645
      (equivalent to a 90% confidence interval [CI]), which was used to define
      cognitive decline. Poisson regression models were built to analyze the
      association between baseline kidney function and cognitive decline. RESULTS: A
      total of 18 (7.3%) cases of incident cognitive decline were observed during the
      follow-up period. After adjusting for potential confounders, the relative risk of
      developing cognitive decline was 4.03 (95% CI 1.09-13.81) among participants with
      an eGFR of 30-59 mL/min/1.73 m2 compared to participants with an eGFR of >=60
      mL/min/1.73 m2. CONCLUSION: Early-stage chronic kidney disease was correlated
      with cognitive decline in an oldest-old Chinese population.

PMID- 28740371
TI  - Influence of environmental factors on food intake among nursing home residents: a
      survey combined with a video approach.
AB  - BACKGROUND: In addition to the well-known physiological factors, dietary behavior
      that affects health seems to be influenced by a wide variety of environmental
      factors. The aim of this study was to assess, by means of an original video
      approach, the influence of the environment on food intake in nursing homes.
      METHODS: The perception of the environment during meals in nursing homes was
      evaluated by residents and by two groups of volunteers who either work in the
      field of geriatrics, or who do not work in the field of geriatrics. First, a
      random sample of residents answered a self-administered questionnaire related to
      different indicators (ie, noise, space, comfort, light, odors, perceived
      satisfaction of meals, taste of meals, presentation of meals, service and
      setting). Second, two separate panels, one including the people who work in the
      field of geriatrics (ie, experts) and one including the people who have no
      particular interest in geriatrics (ie, nonexperts), were asked to answer a
      questionnaire on their perception of the environment after having watched a video
      of the lunch in each nursing home. Then, the food intake of the residents was
      measured by a precise food-weighing method. RESULTS: A total of 88 residents from
      nine different nursing homes, 18 experts and 45 nonexperts answered the
      questionnaires. This study highlighted that, on the one hand, after adjustment on
      confounding variables, the perception of the quantity of food served by the
      residents is the only single factor associated with food consumption (P=0.003).
      On the other hand, experts and nonexperts did not perceive any environmental
      factor that seems to be significantly associated with residents' food intake.
      CONCLUSION: Our results highlighted that, in a nursing home setting,
      environmental factors have limited influence on the food intake of the residents,
      with the exception of their own perception of the quantity served. The relevance
      of this factor deserves further investigation.

PMID- 28740372
TI  - Pharmacological treatment of osteoporosis in the oldest old.
AB  - The incidence of osteoporotic fractures increases with age. Consequently, the
      global prevalence of osteoporotic fractures will increase with the aging of the
      population. In old age, osteoporosis is associated with a substantial burden in
      terms of morbidity and mortality. Nevertheless, osteoporosis in old age continues
      to be underdiagnosed and undertreated. This may, at least partly, be explained by
      the fact that evidence of the antifracture efficacy of osteoporosis treatments
      comes mainly from randomized controlled trials in postmenopausal women with a
      mean age of 70-75 years. However, in the last years, subgroup analyses of these
      landmark trials have been published investigating the efficacy and safety of
      osteoporosis treatment in the very elderly. Based on this evidence, this
      narrative review discusses the pharmacological management of osteoporosis in the
      oldest old (>=80 years). Because of the high prevalence of calcium and/or vitamin
      D deficiency in old age, these supplements are essential in the management of
      osteoporosis in the elderly people. Adding antiresorptive or anabolic treatments
      or combinations, thereof, reduces the risk of vertebral fractures even more, at
      least in the elderly with documented osteoporosis. The reduction of hip fracture
      risk by antiresorptive treatments is less convincing, which may be explained by
      insufficient statistical power in some subanalyses and/or a higher impact of
      nonskeletal risk factors in the occurrence of hip fractures. Compared with
      younger individuals, a larger absolute risk reduction is observed in the elderly
      because of the higher baseline fracture risk. Therefore, the elderly will benefit
      more of treatment. In addition, current osteoporosis therapies also appear to be
      safe in the elderly. Although more research is required to further clarify the
      effect of osteoporosis drugs in the elderly, especially with respect to hip
      fractures, there is currently sufficient evidence to initiate appropriate
      treatment in the elderly with osteoporosis and osteoporotic fractures.

PMID- 28740373
TI  - Glycated hemoglobin A1c-based adjusted glycemic variables in patients with
      diabetes presenting with acute exacerbation of chronic obstructive pulmonary
      disease.
AB  - Acute hyperglycemia is a common finding in patients presenting to emergency
      departments (EDs) with acute exacerbation of chronic obstructive pulmonary
      disease (AECOPD). Several studies have argued against the association between
      hyperglycemia at admission and adverse outcomes in patients with diabetes and an
      acute illness. Recent studies have shown that glucose-related variables (eg,
      glycemic gaps and stress hyperglycemia ratios) that are adjusted for glycated
      hemoglobin levels can indicate the severity of a variety of diseases. The
      objective of this study was to assess whether these hemoglobin A1c (HbA1c)-based
      adjusted average glycemic variables were associated with unfavorable outcomes in
      patients admitted to a hospital with AECOPD. We found that 1) pulmonary infection
      is a major risk factor for AECOPD; 2) a higher glycemic gap and modified stress
      hyperglycemia ratio were associated with the development of acute respiratory
      failure (ARF) in patients with diabetes admitted to an ED because of AECOPD; and
      3) the glycemic gap and modified stress hyperglycemia ratio had superior
      discriminative power over acute hyperglycemia and HbA1c for predicting the
      development of ARF, although the HbA1c-adjusted glycemic variables alone were not
      independent risk factors for ARF.

PMID- 28740374
TI  - Characterization of throat microbial flora in smokers with or without COPD.
AB  - The study aimed to determine the relationship between throat microbiome and COPD.
      Sixty-five Chinese males (n=20, smokers without COPD; n=45 smokers with COPD)
      were included. Nonmetric multidimensional scaling indicated differences of
      microbiome between COPD and controls, but no difference was observed between COPD
      patients with differing degrees of lung function or disease severity. Rarefaction
      analyses suggested that operational taxonomic units (OTUs, species-level)
      richness decreased in COPD. The dominant taxa between COPD and controls were
      similar, but the proportions of taxonomic distribution were different. The
      dominant phyla were Bacteroidetes, Proteobacteria, Firmicutes and Fusobacteria.
      The dominant genera were Haemophilus, Leptotrichia, Porphyromonas, Fusobacterium,
      Veillonella, Streptococcus, Neisseria and Prevotella. Two dominant OTUs, otu3
      (Veillonella_dispar) and otu4 (Streptococcus_unclassified), were identified. Otu3
      and its father-level taxa, which were negatively correlated with predicted
      percent of forced expiratory volume in a second (FEV1%pred), were increased in
      COPD. By contrast, otu4 and its father-level taxa, which were positively
      correlated with FEV1%pred, were decreased in COPD. Otu4 also showed a slight
      potential as a COPD biomarker. To conclude, the throat microbiome was different
      between smokers with or without COPD, which is similar to findings from the lower
      respiratory tract. This study may strengthen our understanding of the
      relationship between microbiomes of different airway sites and COPD.

PMID- 28740375
TI  - Clinical and economic burden of dyspnea and other COPD symptoms in a managed care
      setting.
AB  - PURPOSE: The degree to which symptoms such as dyspnea affect patients with COPD
      is individualized. To address the gap between clinical symptom measures and self
      perceived disease burden, we investigated the symptom status of adult patients
      with COPD and followed with an administrative claims analysis of health care
      resource utilization and costs. METHODS: This was a hybrid US observational study
      consisting of a cross-sectional patient survey followed by a retrospective
      analysis of administrative claims data. The primary COPD symptom measures were
      the modified Medical Research Council (mMRC) Dyspnea scale and the COPD
      Assessment Test (CAT). RESULTS: A total of 673 patients completed the survey. Of
      these, 65% reported mMRC grades 0-1 (low symptomatology) and 35% reported mMRC
      grades 2-4 (high symptomatology); 25% reported CAT score <10 (low symptomatology)
      and 75% reported CAT score >=10 (high symptomatology). More patients with high
      symptomatology (by either measure) had at least one COPD-related inpatient
      hospitalization, emergency room visit, physician office visit, or other
      outpatient services, and filled at least one COPD-related prescription medication
      vs patients with low symptomatology. COPD-related costs were higher for patients
      with high symptomatology than patients with low symptomatology. In a multivariate
      analysis, COPD-related costs were also higher in patients reporting severe
      symptoms. CONCLUSION: Patients with high COPD symptomatology utilized more health
      care resources and had higher COPD-related health care costs during the 6-month
      post-survey period than patients with low symptomatology.

PMID- 28740377
TI  - Mathematical modeling of postcoinfection with influenza A virus and Streptococcus
      pneumoniae, with implications for pneumonia and COPD-risk assessment.
AB  - BACKGROUND: The interaction between influenza and pneumococcus is important for
      understanding how coinfection may exacerbate pneumonia. Secondary pneumococcal
      pneumonia associated with influenza infection is more likely to increase
      respiratory morbidity and mortality. This study aimed to assess exacerbated
      inflammatory effects posed by secondary pneumococcal pneumonia, given prior
      influenza infection. MATERIALS AND METHODS: A well-derived mathematical within
      host dynamic model of coinfection with influenza A virus and Streptococcus
      pneumoniae (SP) integrated with dose-response relationships composed of
      previously published mouse experimental data and clinical studies was implemented
      to study potentially exacerbated inflammatory responses in pneumonia based on a
      probabilistic approach. RESULTS: We found that TNFalpha is likely to be the most
      sensitive biomarker reflecting inflammatory response during coinfection among
      three explored cytokines. We showed that the worst inflammatory effects would
      occur at day 7 SP coinfection, with risk probability of 50% (likely) to develop
      severe inflammatory responses. Our model also showed that the day of secondary SP
      infection had much more impact on the severity of inflammatory responses in
      pneumonia compared to the effects caused by initial virus titers and bacteria
      loads. CONCLUSION: People and health care workers should be wary of secondary SP
      infection on day 7 post-influenza infection for prompt and proper control-measure
      implementation. Our quantitative risk-assessment framework can provide new
      insights into improvements in respiratory health especially, predominantly due to
      chronic obstructive pulmonary disease (COPD).

PMID- 28740376
TI  - Fluticasone propionate/formoterol for COPD management: a randomized controlled
      trial.
AB  - PURPOSE: To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD.
      PATIENTS AND METHODS: COPD patients with forced expiratory volume in 1 s (FEV1)
      <=50% predicted and >=1 moderate/severe COPD exacerbation in the last 12 months
      were randomized to FP/FORM 500/20 or 250/10 ug bid, or formoterol (FORM) 12 ug
      bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe
      COPD exacerbations. RESULTS: In total, 1,765 patients were randomized. There were
      fewer discontinuations with FP/FORM 500/20 ug (20.6%) and 250/10 ug (24.0%)
      compared with FORM (26.1%). None of the two FP/FORM doses reduced the
      moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P<=0.402).
      There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM
      500/20 ug versus FORM in patients with >=2 exacerbations in the preceding year
      (RR: 0.79; P=0.084). Pre- and post-dose FEV1 and forced vital capacity were
      greater with FP/FORM 500/20 ug versus FORM (P<=0.039). There was a trend toward a
      lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate
      with FP/FORM 500/20 ug versus FORM (RR: 0.87; P=0.077). There were more St
      George's Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM
      500/20 ug than FORM (odds ratios [OR] at weeks 6, 23 and 52 >=1.28; P<=0.054).
      EXACT-respiratory symptoms total and breathlessness scores were lower with both
      FP/FORM 500/20 ug and 250/10 ug versus FORM (P<=0.066). Acute beta2-agonist
      induced effects and 24-hour Holter findings were similar for all treatments. Mean
      24-hour urinary cortisol was similarly reduced with both FP/FORM doses.
      Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM
      500/20 ug, FP/FORM 250/10 ug and FORM-treated patients, respectively. Adverse
      events were otherwise similar across treatment groups. CONCLUSION: FP/FORM did
      not reduce exacerbation rates versus FORM. Numerical benefits were observed with
      FP/FORM 500/20 ug versus FORM for secondary variables, including lung function,
      EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and
      breathlessness scores. Few efficacy differences were evident between FP/FORM
      250/10 ug and FORM. Pneumonia was more frequent in FP/FORM-treated patients,
      although the absolute difference was low. Adverse events were otherwise similar
      between treatments.

PMID- 28740378
TI  - Active smoking and COPD phenotype: distribution and impact on prognostic factors.
AB  - PURPOSE: Smoking can affect both the phenotypic expression of COPD and factors
      such as disease severity, quality of life, and comorbidities. Our objective was
      to evaluate if the impact of active smoking on these factors varies according to
      the disease phenotype. PATIENTS AND METHODS: This was a Spanish, observational,
      cross-sectional, multicenter study of patients with a diagnosis of COPD. Smoking
      rates were described among four different phenotypes (non-exacerbators, asthma
      COPD overlap syndrome [ACOS], exacerbators with emphysema, and exacerbators with
      chronic bronchitis), and correlated with disease severity (body mass index,
      obstruction, dyspnea and exacerbations [BODEx] index and dyspnea grade), quality
      of life according to the COPD assessment test (CAT), and presence of
      comorbidities, according to phenotypic expression. RESULTS: In total, 1,610
      patients were recruited, of whom 46.70% were classified as non-exacerbators,
      14.53% as ACOS, 16.37% as exacerbators with emphysema, and 22.40% as exacerbators
      with chronic bronchitis. Smokers were predominant in the latter 2 groups (58.91%
      and 57.67%, respectively, P=0.03). Active smoking was significantly associated
      with better quality of life and a higher dyspnea grade, although differences were
      observed depending on clinical phenotype. CONCLUSION: Active smoking is more
      common among exacerbator phenotypes and appears to affect quality of life and
      dyspnea grade differently, depending on the clinical expression of the disease.

PMID- 28740379
TI  - PEG-coated gold nanoparticles attenuate beta-adrenergic receptor-mediated cardiac
      hypertrophy.
AB  - Gold nanoparticles (AuNPs) are widely used as a drug delivery vehicle, which can
      accumulate in the heart through blood circulation. Therefore, it is very
      important to understand the effect of AuNPs on the heart, especially under
      pathological conditions. In this study, we found that PEG-coated AuNPs attenuate
      beta-adrenergic receptor (beta-AR)-mediated acute cardiac hypertrophy and
      inflammation. However, both isoproterenol, a non-selective beta-AR agonist, and
      AuNPs did not induce cardiac function change or cardiac fibrosis. AuNPs exerted
      an anti-cardiac hypertrophy effect by decreasing beta1-AR expression and its
      downstream ERK1/2 hypertrophic pathway. Our results indicated that AuNPs might be
      safe and have the potential to be used as multi-functional materials (drug
      carrier systems and anti-cardiac hypertrophy agents).

PMID- 28740380
TI  - Inhibition of cell proliferation through an ATP-responsive co-delivery system of
      doxorubicin and Bcl-2 siRNA.
AB  - Herein, DNA duplex was constructed through the hybridization of adenosine
      triphosphate (ATP)-responsive aptamer and its cDNA in which GC-rich motif could
      be used to load doxorubicin (DOX), and then, cationic polymer PEI25K was used as
      a carrier to simultaneously condense DOX-Duplex and Bcl-2 siRNA to prepare the
      ternary nanocomplex polyethylenimine (PEI)/DOX-Duplex/siRNA. The ATP
      concentration gradient between the cytosol and extracellular environment could
      achieve the stable loading of DOX in duplex and the rapid drug release in an ATP
      responsive manner. Using human prostate tumor cell line PC-3 as a model, an
      obvious induction of cell proliferation could be detected with a cell viability
      of 53.3%, which was stronger than single cargo delivery, indicating the
      synergistic effect between these two components. The enhanced anti-proliferative
      effect of ternary nanocomplex could be attributed to the improved induction of
      cell apoptosis in a mitochondria-mediated pathway and cell-cycle arrest at the G2
      phase. Overall, the ATP-responsive nanocarrier for co-delivering DOX and Bcl-2
      siRNA has been demonstrated to be a smart delivery system with favorable anti
      proliferative effect, especially for solving the multidrug resistance of tumors.

PMID- 28740381
TI  - Chitosan-coated diacerein nanosuspensions as a platform for enhancing
      bioavailability and lowering side effects: preparation, characterization, and ex
      vivo/in vivo evaluation.
AB  - Nanodrug delivery systems have been widely reviewed for their use in several drug
      formulations to improve bioavailability, sustain effect, and decrease side
      effects of many candidate drugs. The objective of this study was to evaluate the
      potential of chitosan (CS)-coated nanosuspensions to enhance bioavailability and
      reduce the diarrheal side effect of diacerein (DCN) after oral administration.
      DCN nanosuspensions (DNS) were prepared by sonoprecipitation technique using
      different stabilizers at three different concentrations. The selected DNS with
      optimum particle size (PS), polydispersity index (PDI), and Zeta potential (ZP)
      was coated with three different concentrations of CS-coated DNS (CS-DNS) and
      screened. In vitro dissolution was performed for the selected lyophilized
      formulae and compared with DCN powder in addition to the assessment of drug
      crystallinity via scanning electron microscopy, X-ray powder diffraction, and
      differential scanning calorimetry. Ex vivo drug permeability using noneverted rat
      intestine, intraluminal content, and mucoadhesion evaluation was studied for
      nominated formulae in comparison to DCN suspension. Moreover, in vivo study,
      pharmacokinetic parameters, and evaluation of diarrheal potential were conducted
      after oral administration of selected formulae. Polyvinyl pyrrolidone (PVP)
      stabilized DNS showed a significant increase (P<=0.05) in PS and PDI as the
      stabilizer concentration increased. PVP-stabilized DNS with the lowest CS
      concentration was protected from aggregation by lyophilization with mannitol. A
      remarked enhancement in dissolution parameters was observed in the nanocrystals'
      formulae. Morphological examination and X-ray diffraction confirmed drug
      crystallinity. The intermediate permeation parameters of CS-DNS-F10, lowest rhein
      to-DCN ratio in intraluminal content along with the highest percentage of
      mucoadhesive, could serve as a sustaining profile of coated formula. CS-DNS-F10
      showed a significantly higher Cmax of 0.74+/-0.15 ug/mL at a delayed Tmax of
      3.60+/-0.55 hours with a relative bioavailability of 172.1% compared to DCN
      suspension. CS-coated nanosuspensions could serve as promising revenue to enhance
      bioavailability and reduce the diarrheal side effect of DCN after oral
      administration.

PMID- 28740383
TI  - Enhanced immunization via dissolving microneedle array-based delivery system
      incorporating subunit vaccine and saponin adjuvant.
AB  - PURPOSE: To enhance the immunogenicity of the model subunit vaccine, ovalbumin
      (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the
      toxicity of PD, OVA, and adjuvant were loaded together into liposomes before
      being incorporated into a dissolving microneedle array. METHODS: OVA- and PD
      loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method.
      Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and
      hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD
      Lipos were incorporated into a dissolving microneedle array. The chemical
      stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays
      were investigated. The immune response of Institute of Cancer Research mice and
      potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated.
      RESULTS: The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was
      prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically
      reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was
      incorporated into a dissolving microneedle array. Institute of Cancer Research
      mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune
      response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune
      response in mice, with minimal irritation in rabbit skin. CONCLUSION: The
      dissolving microneedle array-based system is a promising delivery vehicle for
      subunit vaccine and its adjuvant.

PMID- 28740382
TI  - Dual-linker gold nanoparticles as adjuvanting carriers for multivalent display of
      recombinant influenza hemagglutinin trimers and flagellin improve the
      immunological responses in vivo and in vitro.
AB  - Vaccination is the most cost-effective means of infectious disease control.
      Although current influenza vaccines are effective in battling closely matched
      strains, such vaccines have major limitations such as the requirement to produce
      new vaccines every season, an egg-dependent production system, long production
      periods, uncertainty in matching the vaccine to circulating strains, and the
      inability to react to new influenza pandemics resulting from genetic drift or
      shift. To overcome the intrinsic limitations of the conventional influenza
      vaccine, we have designed dual-linker gold nanoparticles (AuNPs) conjugated with
      both recombinant trimetric A/Aichi/2/68 (H3N2), hemagglutinin (HA) and TLR5
      agonist flagellin (FliC) as a novel vaccine approach. Click chemistry and metal
      chelating reactions were used to couple the two proteins. The conjugated proteins
      were found to possess high coupling specificity, high stability in harsh
      environments, high conjugation efficiency, and the ability to keep the
      appropriate protein conformations for immunogenicity and immunostimulation. Both
      AuNPs-HA/FliC and AuNPs-HA formulations induced higher levels of antibody
      responses than a mixture of soluble HA and FliC proteins when administered via a
      single intranasal immunization in mice. To further investigate the adjuvancy of
      these nanoparticles, in vitro experiments were conducted in both the JAWS II
      dendritic cell (DC) line and bone marrow-derived DC (BMDC) models. The results
      showed that dual-conjugated AuNPs were rapidly targeted and taken up by DCs.
      Consequently, DCs were induced toward maturation, as demonstrated by high levels
      of cytokine secretions and membrane costimulatory molecule expression. T cell
      proliferation was observed when splenic T cells were cocultured with AuNPs
      HA/FliC-primed BMDCs. These results suggest that dual-conjugated AuNPs are
      effective at simultaneously displaying antigens and adjuvants in an oriented,
      multivalent format and can promote a strong immune response by activating DCs and
      T cells.

PMID- 28740384
TI  - Tumor microenvironment dual-responsive core-shell nanoparticles with hyaluronic
      acid-shield for efficient co-delivery of doxorubicin and plasmid DNA.
AB  - As the tumor microenvironment (TME) develops, it is critical to take the
      alterations of pH value, reduction and various enzymes of the TME into
      consideration when constructing the desirable co-delivery systems. Herein, TME pH
      and enzyme dual-responsive core-shell nanoparticles were prepared for the
      efficient co-delivery of chemotherapy drug and plasmid DNA (pDNA). A novel pH
      responsive, positively charged drug loading material, doxorubicin (DOX)-4
      hydrazinobenzoic acid (HBA)-polyethyleneimine (PEI) conjugate (DOX-HBA-PEI, DHP),
      was synthesized to fabricate positively charged polyion complex inner core
      DHP/DNA nanoparticles (DDN). Hyaluronic acid (HA) was an enzyme-responsive shell
      which could protect the core and enhance the co-delivery efficiency through CD44
      mediated endocytosis. The HA-shielded pH and enzyme dual-responsive nanoparticles
      (HDDN) were spherical with narrow distribution. The particle size of HDDN was
      148.3+/-3.88 nm and the zeta potential was changed to negative (-18.1+/-2.03 mV),
      which led to decreased cytotoxicity. The cumulative release of DOX from DHP at pH
      5.0 (66.4%) was higher than that at pH 7.4 (30.1%), which indicated the pH
      sensitivity of DHP. The transfection efficiency of HDDN in 10% serum was equal to
      that in the absence of serum, while the transfection of DDN was significantly
      decreased in the presence of 10% serum. Furthermore, cellular uptake studies and
      co-localization assay showed that HDDN were internalized effectively through CD44
      mediated endocytosis in the tumor cells. The efficient co-delivery of DOX and
      pEGFP was confirmed by fluorescent image taken by laser confocal microscope. It
      can be concluded that TME dual-responsive HA-shielded core-shell nanoparticles
      could be considered as a promising platform for the co-delivery of chemotherapy
      drug and pDNA.

PMID- 28740385
TI  - Application of nanodiagnostics in point-of-care tests for infectious diseases.
AB  - Although tremendous efforts have been put into the treatment of infectious
      diseases to prevent epidemics and mortality, it is still one of the major health
      care issues that have a profound impact on humankind. Therefore, the development
      of specific, sensitive, accurate, rapid, low-cost, and easy-to-use diagnostic
      tools is still in urgent demand. Nanodiagnostics, defined as the application of
      nanotechnology to medical diagnostics, can offer many unique opportunities for
      more successful and efficient diagnosis and treatment for infectious diseases. In
      this review, we provide an overview of the nanodiagnostics for infectious
      diseases from nanoparticle-based, nanodevice-based, and point-of-care test (POCT)
      platforms. Most importantly, emphasis focused on the recent trends in the
      nanotechnology-based POCT system. The current state-of-the-art and most promising
      point-of-care nanodiagnostic technologies, including miniaturized diagnostic
      magnetic resonance platform, magnetic barcode assay system, cell phone-based
      polarized light microscopy platform, cell phone-based dongle platform, and paper
      based POCT platform, for infectious diseases were fully examined. The
      limitations, challenges, and future trends of the nanodiagnostics in POCTs for
      infectious diseases are also discussed.

PMID- 28740386
TI  - Quantum dots-based lateral flow immunoassay combined with image analysis for
      semiquantitative detection of IgE antibody to mite.
AB  - Semiquantitative and rapid detection of specific IgE (sIgE) with well clinical
      relevance to house dust mite (HDM) are promising for prevalence rhinitis and
      asthma patients due to the increasing air pollution. However, the conventional
      IgE measurement systems are time-consuming, complicated and require special
      instruments. Herein, we overcome the above limitations of sIgE to HDM detection
      system by developing a quantum dot nanobeads-based lateral flow immunoassay and
      an image analysis procedure. The proposed detection system could
      semiquantitatively measure the IgE in a linear range of 0.2-10 U/mL. Moreover,
      there is a well correlation between the developed detection system and the
      clinical symptoms by a comparison study using 56 positive patients' sera and 40
      healthy control sera. The proposed detection system is simple, robust and easy-to
      use and promising for in home test.

PMID- 28740387
TI  - Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced
      angiogenesis and experimental corneal neovascularization.
AB  - Pathological angiogenesis is one of the major symptoms of severe ocular diseases,
      including corneal neovascularization. The blockade of vascular endothelial growth
      factor (VEGF) action has been recognized as an efficient strategy for treating
      corneal neovascularization. In this study, we aimed to investigate whether
      nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF
      receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental
      corneal neovascularization. Water-insoluble apatinib was encapsulated in
      nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene
      glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG
      (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation,
      scratch wounding migration, and proliferation of human endothelial cells. In a
      rat model of alkali burn injury-induced corneal neovascularization, a
      subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant
      decrease in neovascularization compared to that observed with an injection of
      free apatinib solution or phosphate-buffered saline. An in vivo distribution
      study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs
      revealed the presence of a substantial number of nanoparticles in the corneal
      stroma within 24 h after injection. These in vitro and in vivo results
      demonstrate that apatinib-loaded nanoparticles may be promising for the
      prevention and treatment of corneal neovascularization-related ocular disorders.

PMID- 28740388
TI  - Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells.
AB  - Exosomes, 30-200 nm nanostructures secreted from donor cells and internalized by
      recipient cells, can play an important role in the cellular entry of some
      viruses. These microvesicles are actively secreted into various body fluids,
      including blood, urine, saliva, cerebrospinal fluid, and breast milk. We
      successfully isolated exosomes from human breast milk and plasma. The size and
      concentration of purified exosomes were measured by nanoparticle tracking, while
      Western blotting confirmed the presence of the exosomal-associated proteins CD9
      and CD63, clathrin, and T cell immunoglobulin and mucin proteins (TIMs). Through
      viral infection assays, we determined that HIV-1 utilizes an exosome-dependent
      mechanism for entry into human immune cells. The virus contains high amounts of
      phosphatidylserine (PtdSer) and may bind PtdSer receptors, such as TIMs. This
      mechanism is supported by our findings that exosomes from multiple sources
      increased HIV-1 entry into T cells and macrophages, and viral entry was potently
      blocked with anti-TIM-4 antibodies.

PMID- 28740389
TI  - Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy,
      and clinical necessity.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder
      characterized by hyperactivity and/or inattention and is often associated with a
      substantial impact on psychosocial functioning. Methylphenidate (MPH), a central
      nervous system stimulant, is commonly used for pharmacological treatment of
      adults and children with ADHD. Current practice guidelines recommend optimizing
      MPH dosage to individual patient needs; however, the clinical benefits of
      individual dose optimization compared with fixed-dose regimens remain unclear.
      Here we review the available literature on MPH dose optimization from clinical
      trials and real-world experience on ADHD management. In addition, we report
      safety and efficacy data from the largest MPH modified-release long-acting Phase
      III clinical trial conducted to examine benefits of dose optimization in adults
      with ADHD. Overall, MPH is an effective ADHD treatment with a good safety
      profile; data suggest that dose optimization may enhance the safety and efficacy
      of treatment. Further research is required to establish the extent to which short
      term clinical benefits of MPH dose optimization translate into improved long-term
      outcomes for patients with ADHD.

PMID- 28740390
TI  - Brain regions associated with anosognosia for memory disturbance in Alzheimer's
      disease: a magnetic resonance imaging study.
AB  - BACKGROUND AND OBJECTIVE: Patients with Alzheimer's disease (AD) are frequently
      unaware of their cognitive symptoms and medical diagnosis. The term "anosognosia"
      is used to indicate a general lack of awareness of one's disease or disorder. The
      neural substrate underlying anosognosia in AD is unclear. Since anosognosia for
      memory disturbance might be an initial sign of AD, it is important to determine
      the neural correlates. This study was designed to investigate the characteristics
      and neural correlates of anosognosia for memory disturbance in patients with mild
      AD. METHODS: The subjects were 49 patients with mild AD who participated in a
      retrospective cross-sectional study. None of the patients had been treated with
      cholinesterase inhibitors, memantine, or psychotropic drugs. All patients
      underwent magnetic resonance imaging (MRI). Anosognosia for memory disturbance
      was assessed based on the discrepancy between questionnaire scores of patients
      and their caregivers. Structural MRI data were analyzed to explore the
      association between anosognosia and brain atrophy, using a voxel-based approach.
      Statistical parametric mapping software was used to explore neural correlations.
      In image analysis, multiple regression analysis was performed to examine the
      relationship between anosognosia score and regional gray matter volume. Age,
      years of education, and total intracranial volume were entered as covariates.
      RESULTS: The anosognosia score for memory disturbance was significantly
      negatively correlated with gray matter volume in the left superior frontal gyrus.
      CONCLUSION: The left superior frontal gyrus was involved in anosognosia for
      memory disturbance, while the medial temporal lobe, which is usually damaged in
      mild AD, was not associated with anosognosia. The left superior frontal gyrus
      might be an important region for anosognosia in mild AD.

PMID- 28740391
TI  - Attention-memory training yields behavioral and academic improvements in children
      diagnosed with attention-deficit hyperactivity disorder comorbid with a learning
      disorder.
AB  - BACKGROUND: Recent studies have suggested that children with attention-deficit
      hyperactivity disorder (ADHD) may benefit from computerized cognitive training.
      Therapy implementation is especially complicated when ADHD is associated with
      learning disorders (LDs). This study tested the efficacy of a computer-based
      cognitive training program, namely, computerized cognitive training (CCT), in
      children with ADHD comorbid with an LD (ADHD-LD), with or without psychostimulant
      medication. MATERIALS AND METHODS: After diagnostic evaluations, 27 children with
      ADHD-LD (8 unmedicated and 19 medicated) participated in CCT, which is intended
      to improve attention, memory, reasoning, visual processing, and executive
      functioning. The participants completed 24 1-hour sessions over 3 months.
      Neuropsychometric and standardized academic test results before and after
      training were compared to assess treatment efficacy. Shapiro-Wilk normality tests
      were applied, and subsequent Wilcoxon tests were used to identify significant
      differences in pre-versus post-training performance. RESULTS: After CAT, children
      diagnosed with ADHD-LD showed 1) improvements in trained skills, measured
      directly within the software and indirectly by external psychometric tests; 2)
      improvements in attention, memory, and some executive functioning; 3)
      improvements in academic performance, particularly in mathematics; and 4)
      reductions in maladaptive behavioral features. CONCLUSION: The present findings
      suggest that cognitive training programs should be explored further as potential
      adjunctive therapies to improve outcomes in children with ADHD-LD.

PMID- 28740392
TI  - Cholecalciferol improves glycemic control in type 2 diabetic patients: a 6-month
      prospective interventional study.
AB  - BACKGROUND AND PURPOSE: To investigate the effects of vitamin D supplementation
      on glucose homeostasis and lipid profile in type 2 diabetic patients who have
      vitamin D deficiency. PATIENTS AND METHODS: One hundred twenty-five type 2
      diabetic patients taking oral hypoglycemic agents as mono- or combination therapy
      were recruited from the diabetes and endocrinology clinic. Subject demographics,
      duration of diabetes, antidiabetic medication, body mass index (BMI), pulse, and
      blood pressure (BP) were assessed. Laboratory measurements of serum vitamin D3
      level, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and lipid profile
      were measured. Homeostatic model assessment-insulin resistance (HOMA-IR) was
      calculated whenever fasting insulin (FI) was available. Forty-one patients (27
      males and 14 females) were started on cholecalciferol replacement-45,000 units
      once weekly for 8 weeks and then 22,500 units once weekly for 16 weeks. Calcium
      carbonate tablets 500 mg once daily were also prescribed for the initial 2 months
      of treatment. Measured variables were reassessed after 6 months of replacement
      therapy. During the trial, subjects were instructed not to change their diabetes
      drugs or lifestyle. RESULTS: No significant association was found between vitamin
      D3 level and any of the measured variables apart from a significant positive
      correlation with blood urea nitrogen. Vitamin D3 replacement was associated with
      a significant increase in its level (14.0+/-4.0 vs 31.0 vs 7.9 ng/mL, P<0.001).
      This was associated with a significant reduction of HbA1c (7.9+/-1.7 vs 7.4%+/
      1.2%, P=0.001) and FPG (9.1+/-4.3 vs 7.9+/-2.4 mmol/L, P=0.034). Mean reduction
      of HbA1c was 0.54% and that of FPG was 1.22 mmol/L. FI, c-peptide and insulin
      resistance (IR) were reduced but this was statistically insignificant (P=0.069,
      0.376, 0.058, respectively). FI decreased by 22%, HOMA-IR by 27.6%, and c-peptide
      by 1.83%. Total cholesterol, low-density lipoprotein cholesterol, parathyroid
      hormone, alkaline phosphatase, serum creatinine, and pulse rate significantly
      decreased (4.3+/-0.9 vs 4.0+/-0.9 mmol/L, P=0.036; 2.5+/-0.8 vs 2.2+/-0.8 mmol/L,
      P=0.018; 4.6+/-2.1 vs 3.5+/-1.8 pmol/L, P=0.001; 82.1+/-26.2 vs 66.2+/-19.5 U/L,
      P<0.001; 74.6+/-15.6 vs 70.7+/-14.7 MUmol/L, P=0.047; and 81.6+/-11.9 vs 77.5+/
      12.0 bpm, P=0.045, respectively). Triglycerides and high-density lipoprotein
      cholesterol, both systolic and diastolic BP, and BMI did not show significant
      change. CONCLUSION: Cholecalciferol helps improve blood glucose control and
      cholesterol profile in vitamin D3-deficient type 2 diabetic patients.

PMID- 28740393
TI  - Current evidence for the use of C-MAC videolaryngoscope in adult airway
      management: a review of the literature.
AB  - The C-MAC videolaryngoscope is the first Macintosh-typed videolaryngoscope. Since
      the advent of its original version video Macintosh system in 1999, this device
      has been modified several times. A unique feature of C-MAC device is its ability
      to provide the 2 options of direct and video laryngoscopy with the same device.
      The available evidence shows that in patients with normal airways, C-MAC
      videolaryngoscope compared with direct laryngoscopy can provide comparable or
      better laryngeal views and exerts less force on maxillary incisors, but does not
      offer conclusive benefits with regard to intubation time, intubation success,
      number of intubation attempts, the use of adjuncts, and hemodynamic responses to
      intubation. In patients with predicted or known difficult airways, C-MAC
      videolaryngoscope can achieve a better laryngeal view, a higher intubation
      success rate and a shorter intubation time than direct laryngoscopy. Furthermore,
      the option to perform direct and video laryngoscopy with the same device makes C
      MAC videolaryngoscope exceptionally useful for emergency intubation. In addition,
      the C-MAC videolaryngoscope is a very good tool for tracheal intubation teaching.
      However, tracheal intubation with C-MAC videolaryngoscope may occasionally fail
      and introduction of C-MAC videolaryngoscope in clinical practice must be
      accompanied by formal training programs in normal and difficult airway
      managements.

PMID- 28740394
TI  - A case of iatrogenic pneumothorax in which chest tube placement could be avoided
      by intraoperative evaluation with transthoracic ultrasonography.
AB  - We report a case of iatrogenic pneumothorax in which chest tube placement was
      avoided by continuous intraoperative evaluation with transthoracic
      ultrasonography. A 53-year-old man had undergone a subsegmentectomy. While
      attempting to place a central venous catheter in the right internal jugular vein
      after the induction of anesthesia, we identified gas absorption during the
      puncture and suspected a pneumothorax. Chest X-ray revealed an ~5-mm collapse of
      the right lung apex. Tension pneumothorax was a concern during surgery because of
      the long-term positive pressure ventilation, but we decided to start the
      operation without preventative chest tube placement. During the operation, we
      regularly observed the midclavicular line of the second intercostal space using
      ultrasound. The operation was completed uneventfully. In this case, we
      effectively utilized ultrasound and avoided preventive chest tube placement and
      the associated complications. Transthoracic ultrasonography could be performed
      easily and continuously during surgery and was effective for evaluating the
      progression of an intraoperative pneumothorax.

PMID- 28740395
TI  - Diagnostic reliability of pediatric appendicitis score, ultrasound and low-dose
      computed tomography scan in children with suspected acute appendicitis.
AB  - BACKGROUND: Diagnosis of appendicitis in children is clinically challenging.
      Computed tomography (CT) is the gold standard for diagnosis; however, radiation
      exposure early in life is a concern with this technique. Therefore, in this
      study, we aimed to evaluate the diagnostic reliability of low-dose CT, pediatric
      appendicitis score (PAS), and abdominal ultrasound (US) in children with acute
      appendicitis, to reach a safe diagnosis. PATIENTS AND METHODS: This retrospective
      study was conducted on 140 children who were admitted with clinically suspected
      acute appendicitis (45 with positive appendicitis and 95 children with negative
      appendicitis). Low-dose CT was performed, and PAS was retrospectively calculated
      for all subjects. US was initially performed for 38 subjects. All results were
      compared with the final diagnosis reached by an operative, histopathological
      analysis and follow-up. RESULTS: Low-dose CT showed a sensitivity, specificity,
      and accuracy of 97.8%, 100%, and 99.3%, respectively. At a cutoff value >=5, PAS
      showed a sensitivity, specificity, and accuracy of 95%, 84%, and 89%,
      respectively. Abdominal US examination showed sensitivity, specificity, and
      accuracy of 55.6%, 85%, and 71%, respectively. Implementing Poortman's model
      resulted in higher accuracy (92%) of US. There was a significant difference in
      accuracy between a low-dose CT and PAS on one side and between Poortman's model
      and US examination on the other side. A diagnostic scheme was suggested using PAS
      as the excluding tool (PAS <=2 send home and >=7 send directly to operation)
      followed by US examination and reserving low-dose CT for inconclusive cases. This
      scheme would eliminate the use of CT for at least 33.7% and in 7 cases who had
      initial US examination. CONCLUSION: Although CT remains the most accurate and
      less operator-dependent diagnostic tool for pediatric appendicitis, the radiation
      hazards could however be minimized using PAS as an excluding tool and US as the
      primary imaging modality followed by low-dose CT for inconclusive cases only.

PMID- 28740396
TI  - Antithrombotic prophylaxis of atrial fibrillation in an Italian real-world
      setting: a retrospective study.
AB  - OBJECTIVES: The aims of this study were to assess the prevalence of diagnosed
      atrial fibrillation (AF), the drug use in patients with AF in terms of
      antithrombotic (AT) strategies used and the compliance with treatment, and to
      describe the characteristics of patients affected by AF in relation to treatment.
      METHODS: The data collected were provided from databases of general practitioners
      (GPs) of the Local Health Unit of Bologna in Italy. From January 1, 2009, to
      December 31, 2012, all subjects aged >=18 years followed by the 44 GPs enrolled
      in the study were evaluated, and the subjects with a diagnosis of AF were
      included in the analysis. RESULTS: From 2009 to 2012, we identified 1,413
      patients with a diagnosis of AF (2.09% of 67,517 patients of the 44 GPs). A total
      of 1,413 patients with a diagnosis of AF (2.09% of 67,517 patients of the 44 GPs)
      were enrolled in the study. During the study, 14% of the enrolled patients did
      not receive any prescription of ATs, 30% and 39.56% were treated only with
      antiplatelet (AP) agents and oral anticoagulants (OACs), respectively, and 16.28%
      of the patients received prescriptions for both an OAC and an AP agent; of the
      patients receiving prescriptions for both, only 4.17% received these therapies at
      the same time. Among the OAC users, the percentage of patients still on treatment
      with the index drug during the last 3 months of observation was 76.9%.
      CONCLUSION: Our findings emphasize that in an Italian real-world setting, the
      burden of AF in general population from a public health point of view underscores
      the need for improvement in utilization of appropriate ATs in patients with known
      AF.

PMID- 28740397
TI  - Eligibility for alirocumab or evolocumab treatment in 1090 hypercholesterolemic
      patients referred to a regional cholesterol treatment center with LDL cholesterol
      >=70 mg/dL despite maximal-tolerated LDL-cholesterol-lowering therapy.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors, Praluent
      (alirocumab [ALI]) and Repatha (evolocumab [EVO]) have been approved as adjuncts
      to the standard-of-care maximal-tolerated dose (MTD) of low-density lipoprotein
      cholesterol (LDLC)-lowering therapy (LLT), statin therapy, in heterozygous (HeFH)
      (ALI or EVO) or homozygous (EVO) familial hypercholesterolemia, or clinical
      atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient
      (both). Since LDLC lowering has been revolutionized by ALI and EVO, specialty
      pharmaceutical pricing models will be applied to a mass market. METHODS: We
      applied US Food and Drug Administration (FDA) and insurance eligibility criteria
      for ALI and EVO to 1090 hypercholesterolemic patients serially referred over 3
      years who then received >=2 months maximal-tolerated dose of standard-of-care LDL
      cholesterol-lowering therapy (MTDLLT) with follow-up LDLC >=70 mg/dL. MTDLLT did
      not include ALI or EVO, which had not been commercially approved before
      completion of this study. RESULTS: Of the 1090 patients, 140 (13%) had HeFH by
      clinical diagnostic criteria and/or CVD with LDLC >100 mg/dL despite >=2 months
      on MTDLLT, meeting FDA insurance criteria for ALI or EVO therapy. Another 51 (5%)
      patients were statin intolerant, without HeFH or CVD. CONCLUSION: If 13% of
      patients with HeFH-CVD and LDLC >100 mg/dL despite MTDLLT are eligible for ALI or
      EVO, then specialty pharmaceutical pricing models (~$14,300/year) might be used
      in an estimated 10 million HeFH-CVD patients. Whether the health care savings
      arising from the anticipated reduction of CVD events by ALI or EVO justify their
      costs in populations with HeFH-CVD and LDLC >100 mg/dL despite MTDLLT remains to
      be determined.

PMID- 28740398
TI  - Focusing on a complete blood cell parameter: mean platelet volume levels may be a
      predictor of coronary slow flow.
AB  - BACKGROUND: The relationship between increased mean platelet volume (MPV) and
      atherosclerosis is well known. In the present study, MPV in patients with
      coronary slow flow (CSF) and in cases with normal coronary anatomy (NCA) was
      investigated and compared with the aim of identifying the relationship between
      CSF and MPV. PATIENTS AND METHODS: We studied 40 patients previously determined
      via coronary angiography as having NCA and 40 patients with CSF in the coronary
      blood stream, as identified by thrombolysis in myocardial infarction square.
      Thus, a total of 80 patients from the Elazig Education and Research Hospital
      (Elazig, Turkey) were included in the present study retrospectively and
      laboratory and anamnesis information was scanned into their files. The
      relationship between MPV and CSF was studied. RESULTS: MPV levels were observed
      to be significantly higher in the CSF group compared to the NCA group (10.05+/
      1.3 and 8.6+/-0.6, p<0.001). In receiver operating characteristics analyses, it
      was determined that an MPV >9.05 measured in CSF patients at application had a
      predictive specificity of 77.5% and sensitivity of 77.5% for CSF (area under the
      curve: 0.825, 95% confidence interval [CI]: 0.726-0.924, p<0.0001). It was found
      that MPV level was an independent predictor of CSF (beta=-600, p<0.001, 95% CI: 
      0.383 to -0.176). CONCLUSION: MPV is increased in patients with CSF when compared
      to patients with NCA. This finding supports the fact that MPV could be a
      predictor of CSF.

PMID- 28740399
TI  - A safety culture assessment by mixed methods at a public maternity and infant
      hospital in China.
AB  - OBJECTIVE: To assess safety culture at a public maternity hospital in Shanghai,
      China, using a sequential mixed methods approach. The study was part of a bigger
      study looking at the application of the mixed methods approach to assess safety
      culture in health care in different organizations and countries. METHODOLOGY: A
      mixed methods approach was utilized by first distributing the Safety Attitudes
      Questionnaire measuring six safety culture dimensions and five independent items
      to all hospital staff (n=1482) working in 18 departments at a single hospital.
      Afterward, semistructured interviews were conducted using convenience sampling,
      where 48 hospital staff from nine departments at the same hospital were
      individually interviewed. RESULTS: The survey received a response rate of 96%.
      The survey findings show significant differences between the hospital departments
      in almost all safety culture dimensions and independent items. Similarly, the
      interview findings revealed that there were different, competing priorities
      between departments perceived to result in a reduced quality of collaboration and
      bottlenecks in care delivery. Another major finding was that staff who worked
      more hours per week would perceive working conditions significantly more
      negatively. Issues related to working conditions were also the most common
      concerns discussed in the interviews, especially the issue on high workload. High
      workload was also reflected in the fact that 91.45% of survey respondents
      reported that they worked 40 hours or longer per week. Finally, interview
      findings complemented survey findings, thus providing a more complete and
      accurate picture of safety culture. CONCLUSION: Hospital leaders need to
      prioritize interventions focused on improving the quality of cross-department
      collaboration and reducing workload. A mixed methods assessment of safety culture
      provides more meaningful, targeted results, enabling leaders to prioritize and
      tailor improvement efforts to increase the impact of an intervention.

PMID- 28740400
TI  - Multidisciplinary care of craniosynostosis.
AB  - The management of craniosynostosis, especially in the setting of craniofacial
      syndromes, is ideally done in a multidisciplinary clinic with a team focused
      toward comprehensive care. Craniosynostosis is a congenital disorder of the
      cranium, caused by the premature fusion of one or more cranial sutures. This
      fusion results in abnormal cranial growth due to the inability of the involved
      sutures to accommodate the growing brain. Skull growth occurs only at the patent
      sutures, resulting in an abnormal head shape. If cranial growth is severely
      restricted, as seen in multisuture craniosynostosis, elevation in intracranial
      pressure can occur. Whereas most patients treated in a multidisciplinary
      craniofacial clinic have non-syndromic or isolated craniosynostosis, the most
      challenging patients are those with syndromic craniosynostosis. The purpose of
      this article was to discuss the multidisciplinary team care required to treat
      both syndromic and non-syndromic craniosynostosis.

PMID- 28740401
TI  - The diagnostic and prognostic values of Ki-67/MIB-1 expression in thyroid cancer:
      a meta-analysis with 6,051 cases.
AB  - BACKGROUND: Growing evidence has demonstrated that Ki-67/MIB-1 has an effect on
      the clinical progression and prognosis in cancers. However, the diagnostic and
      prognostic values of Ki-67/MIB-1 in thyroid cancer remain unclear. MATERIALS AND
      METHODS: The meta-analysis was conducted in accordance with Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses guidelines. Studies were retrieved
      from PubMed, EBSCO, EMBASE, ISI Web of Science, China National Knowledge
      Infrastructure, WanFang and Chinese VIP databases. MetaDiSc and STATA12.0 were
      used to analyze the meta-analysis. Fixed-effect analysis and random-effect
      analysis were applied to pool the relative ratio based on heterogeneity in this
      meta-analysis. RESULTS: In the meta-analysis, 51 eligible studies were included.
      The pooled sensitivity of Ki-67/MIB-1 was 0.61 (95% confidence interval [CI]:
      0.59-0.63) and specificity was 0.75 (95% CI: 0.74-0.77) in thyroid cancer. The
      pooled positive likelihood ratio was 3.19 (95% CI: 2.30-4.42) and negative
      likelihood ratio was 0.43 (95% CI: 0.35-0.54). In the diagnosis of thyroid
      cancer, the pooled diagnostic odds ratio of Ki-67/MIB-1 was 8.54 (95% CI: 5.03
      14.49). The area under the symmetric receiver operating characteristic curve was
      0.804 (standard error =0.031). Our results showed that there were statistical
      associations between Ki-67/MIB-1 and age (odds ratio [OR] =1.71, 95% CI: 1.14
      2.57, P=0.010), tumor size (OR =1.86, 95% CI: 1.17-2.96, P=0.008), lymph node
      metastasis (OR =2.49, 95% CI: 1.42-4.39, P=0.002), metastasis status (OR =6.96,
      95% CI: 2.46-19.69, P<0.001), tumor node metastasis stage (OR =6.56, 95% CI: 3.80
      11.34, P<0.001) and extrathyroid extension (OR =1.91, 95% CI: 1.27-2.87,
      P=0.002). Furthermore, thyroid cancer patients with a high level of Ki-67/MIB-1
      had a worse disease-free survival as compared to patients with a low level of Ki
      67/MIB-1 (hazard ratio =5.19, 95% CI: 3.18-8.46, P<0.001). Also, Ki-67/MIB-1 was
      found to be associated with increased risk of mortality (hazard ratio =3.56, 95%
      CI: 1.17-10.83, P=0.025). CONCLUSION: Our results demonstrated that Ki-67/MIB-1
      might act as a potential factor in diagnosing thyroid cancer in Chinese. Also,
      the meta-analysis indicated that Ki-67/MIB-1 might have an effect on prognosis in
      non-Chinese thyroid cancer patients.

PMID- 28740402
TI  - Therapeutic value of 3-D printing template-assisted 125I-seed implantation in the
      treatment of malignant liver tumors.
AB  - OBJECTIVE: To explore the therapeutic value of 3-D printing template-assisted
      125I-seed implantation in the treatment of malignant liver tumors. MATERIALS AND
      METHODS: Fifteen liver cancer patients with 47 total lesions were treated with 3
      D printing template-assisted radioactive seed implantation (group A), and 25
      liver-tumor patients with 66 total lesions were treated with 125I-seed
      implantation without a template auxiliary (group B). Operation time, in-hospital
      time, operation complications, dose distribution, and response rate (number) were
      compared between the two groups. RESULTS: Shorter operation times and better dose
      distribution were observed in group A than in group B, and the differences were
      statistically significant. The response rate after 2 months was 86.7% (13 of 15)
      in group A and 84% (21 of 25) in group B; differences between the two groups were
      not significant. CONCLUSION: Application of 3-D printing template-assisted
      radioactive seed implantation in the treatment of malignant liver tumors can help
      shorten operation time and optimize radiation-dose distribution, is worthy of
      further study, and has clinical significance.

PMID- 28740403
TI  - Primary lung sarcoma treated with stereotactic ablative radiotherapy: a case
      report.
AB  - Primary lung sarcoma (PLS) is an extremely rare, very aggressive malignancy.
      Surgical removal is considered the treatment of choice, and patients who have
      been given conventional radiotherapy have had inferior outcomes. This study is
      the first describing a case of PLS treated with stereotactic ablative
      radiotherapy (SABR), which precisely targets a small tumor with a markedly higher
      biologically effective dose than conventional radiotherapy. The patient was an 82
      year-old man who was diagnosed with primary lung leiomyosarcoma based on
      radiology, pathology, and immunohistochemical examinations. The PLS was located
      in the right lower lobe and measured 2.5 cm. No regional nodal or distant organ
      metastasis was observed. He was inoperable medically. The SABR was performed
      using volumetric modulated arc therapy and a dose of 56 Gy in four fractions.
      Follow-up computed tomography 2 months after SABR revealed a complete tumor
      response. The toxicity was limited to mild respiratory symptoms. The patient is
      alive and has had no evidence of disease for 2 years. This study suggests that
      SABR can be a safe and effective treatment option for PLS.

PMID- 28740404
TI  - Reactive oxygen species mediate soft corals-derived sinuleptolide-induced
      antiproliferation and DNA damage in oral cancer cells.
AB  - We previously reported that the soft coral-derived bioactive substance,
      sinuleptolide, can inhibit the proliferation of oral cancer cells in association
      with oxidative stress. The functional role of oxidative stress in the cell
      killing effect of sinuleptolide on oral cancer cells was not investigated as yet.
      To address this question, we introduced the reactive oxygen species (ROS)
      scavenger (N-acetylcysteine [NAC]) in a pretreatment to evaluate the
      sinuleptolide-induced changes to cell viability, morphology, intracellular ROS,
      mitochondrial superoxide, apoptosis, and DNA damage of oral cancer cells (Ca9
      22). After sinuleptolide treatment, antiproliferation, apoptosis-like morphology,
      ROS/mitochondrial superoxide generation, annexin V-based apoptosis, and gammaH2AX
      based DNA damage were induced. All these changes were blocked by NAC pretreatment
      at 4 mM for 1 h. This showed that the cell-killing mechanism of oral cancer cells
      of sinuleptolide is ROS dependent.

PMID- 28740405
TI  - Novel agents for the treatment of childhood leukemia: an update.
AB  - Achieving lower morbidity and higher survival rates in the treatment of childhood
      leukemia has been a paradigm of success in modern oncology. However, serious long
      term health complications occur in very large populations of childhood leukemia
      survivors, in the case of both acute lymphoid leukemia and acute myeloid leukemia
      (AML). Additionally, 15% of acute lymphoid leukemia patients have treatment
      failures, and rates are even higher in childhood AML. In the last few decades, as
      a result of well-tested experiments that statistically analyzed treatment
      cohorts, new agents have emerged as alternatives or supplements to established
      treatments, in which high survival and/or less morbidity were observed. This
      review provides an overview of better practice in the treatment of childhood
      leukemia.

PMID- 28740406
TI  - Conventional real-time PCR-based detection of T790M using tumor tissue or blood
      in patients with EGFR TKI-resistant NSCLC.
AB  - Blood biopsy has many advantages over tissue biopsy for diagnosing acquired T790M
      mutation in patients with non-small-cell lung cancer, such as being less risky
      and painful. New techniques with high sensitivity (eg, droplet digital PCR) show
      promising results during blood biopsy, but the positive rates of identification
      are still quite unclear. Whether there are other factors, except technology,
      affecting the results of blood biopsy is unclear. In this study, we used
      conventional amplification refractory mutation system to detect tumor tissue or
      blood for T790M mutation in patients clinically resistant to tyrosine kinase
      inhibitors. A total of 45 patients treated at West China Hospital between 2014
      and 2016 were analyzed. The positive rate of T790M mutation was 70.8% based on
      tissue biopsy and 37.5% based on blood biopsy. Of the 24 patients whose epidermal
      growth factor receptor gene was genotyped through tissue and blood biopsy, 10
      (41.7%) were concordant for T790M mutation status (kappa=0.006). Of the 17
      patients positive for T790M by tissue biopsy, 7 (41.2%) were positive for T790M
      by blood biopsy, and 3 of these 7 were only weakly positive. Of the 7 patients
      negative for T790M by tissue biopsy, 2 (28.6%) were positive by blood biopsy. Our
      T790M detection rate is higher than that reported by other studies using digital
      droplet PCR. These results suggest that other factors (eg, clinical features),
      intrinsically connected with circulating tumor DNA level, also affect the results
      of blood biopsy, and thus cannot be controlled through technological
      optimization.

PMID- 28740407
TI  - Comparison of a mouse and a novel human scFv-SNAP-auristatin F drug conjugate
      with potent activity against EGFR-overexpressing human solid tumor cells.
AB  - Antibody-drug conjugates (ADCs) can deliver toxins to specific targets such as
      tumor cells. They have shown promise in preclinical/clinical development but
      feature stoichiometrically undefined chemical linkages, and those based on full
      size antibodies achieve only limited tumor penetration. SNAP-tag technology can
      overcome these challenges by conjugating benzylguanine-modified toxins to single
      chain fragment variables (scFvs) with 1:1 stoichiometry while preserving antigen
      binding. Two (human and mouse) scFv-SNAP fusion proteins recognizing the
      epidermal growth factor receptor (EGFR) were expressed in HEK 293T cells. The
      purified fusion proteins were conjugated to auristatin F (AURIF). Binding
      activity was confirmed by flow cytometry/immunohistochemistry, and cytotoxic
      activity was confirmed by cell viability/apoptosis and cell cycle arrest assays,
      and a novel microtubule dynamics disassembly assay was performed. Both ADCs bound
      specifically to their target cells in vitro and ex vivo, indicating that the
      binding activity of the scFv-SNAP fusions was unaffected by conjugation to AURIF.
      Cytotoxic assays confirmed that the ADCs induced apoptosis and cell cycle arrest
      at nanomolar concentrations and microtubule disassembly. The SNAP-tag technology
      provides a platform for the development of novel ADCs with defined conjugation
      sites and stoichiometry. We achieved the stable and efficient linkage of AURIF to
      human or murine scFvs using the SNAP-tag technology, offering a strategy to
      improve the development of personalized medicines.

PMID- 28740408
TI  - Induction chemotherapy followed by intensity-modulated radiotherapy with reduced
      gross tumor volume delineation for stage T3-4 nasopharyngeal carcinoma.
AB  - PURPOSE: A common problem in stage T3-4 nasopharyngeal carcinoma (NPC) is the
      narrow gap between the primary tumor and neurological structures, which makes
      dose optimization difficult. Considering that significant tumor shrinkage may
      occur during induction chemotherapy (IC), this study explored the efficacy of
      intensity-modulated radiotherapy (IMRT) using reduced gross tumor volume (GTV) in
      the treatment of T3-4 NPC. PATIENTS AND METHODS: Between January 2009 and April
      2014, 103 patients with non-metastatic stage T3-4 NPC were prospectively
      recruited. They were assigned to accept IC, followed by reduced-volume IMRT and
      adjuvant chemotherapy. GTV was based on the post-IC volume of intracavity tumors
      and lymph nodes, and the pre-IC volume of the remaining involved structures.
      RESULTS: For all treated patients, the 3-year local failure-free survival (LFFS)
      was 91.9%. After IC, 91 (88.3%) patients achieved local objective response (OR),
      and their 3-year LFFS rates were significantly better than in patients who failed
      to achieve local OR (94.1% vs 75.0%, P=0.023). A multivariate analysis
      demonstrated the prognostic value of tumor response to IC for LFFS. Dosimetric
      analysis showed good homogeneity, and the dose constraints were stringent.
      Asymptomatic temporal lobe necrosis in the ipsilateral side of tumor occurred in
      one patient. CONCLUSION: IMRT using a reduced GTV delineation delivered
      satisfactory doses to the target volumes and avoided overdosing of critical
      neurological structures. Results showed satisfactory survival outcomes with few
      treatment-related toxicities. Tumor response to IC could facilitate selection of
      patients with stage T3-4 NPC eligible for treatment with this method.

PMID- 28740409
TI  - Hair follicle growth by stromal vascular fraction-enhanced adipose
      transplantation in baldness.
AB  - Great interest remains in finding new and emerging therapies for the treatment of
      male and female pattern hair loss. The autologous fat grafting technique is >100
      years old, with a recent and dramatic increase in clinical experience over the
      past 10-15 years. Recently, in 2001, Zuk et al published the presence of adipose
      derived stem cells, and abundant research has shown that adipose is a complex,
      biological active, and important tissue. Festa et al, in 2011, reported that
      adipocyte lineage cells support the stem cell niche and help drive the complex
      hair growth cycle. Adipose-derived regenerative cells (also known as stromal
      vascular fraction [SVF]) is a heterogeneous group of noncultured cells that can
      be reliably extracted from adipose by using automated systems, and these cells
      work largely by paracrine mechanisms to support adipocyte viability. While,
      today, autologous fat is transplanted primarily for esthetic and reconstructive
      volume, surgeons have previously reported positive skin and hair changes
      posttransplantation. This follicular regenerative approach is intriguing and
      raises the possibility that one can drive or restore the hair cycle in male and
      female pattern baldness by stimulating the niche with autologous fat enriched
      with SVF. In this first of a kind patient series, the authors report on the
      safety, tolerability, and quantitative, as well as photographic changes, in a
      group of patients with early genetic alopecia treated with subcutaneous scalp
      injection of enriched adipose tissue. The findings suggest that scalp stem cell
      enriched fat grafting may represent a promising alternative approach to treating
      baldness in men and women.

PMID- 28740410
TI  - Genotyping of HBV and tracking of resistance mutations in treatment-naive
      patients with chronic hepatitis B.
AB  - BACKGROUND AND AIMS: Resistance mutation analogs to nucleos(t)ides have been
      described in treatment-naive patients with chronic hepatitis B (CHB), with
      clinical implications. The aim of this study was to investigate primary
      resistance mutations and genotypes circulating in patients naive to chronic
      hepatitis B, in the Northern and Northeastern regions of Brazil. METHODS: We
      conducted a study of resistance mutations and genotypic characterization of
      hepatitis B virus (HBV) in 189 treatment-naive patients chronically infected with
      HBV. RESULTS: Drug resistance-associated mutations located in the RT domain of
      the P gene (rtHBV) were found in 6% of the treatment-naive patients from the
      Northeastern Region. The mutations were rtA194T, rtL180M + rtM204V, rtS202I,
      rtM204I, and rtA181S. No patient in the Northern Region had the resistance
      mutation. In the gene S region, the frequency of vaccine escape mutations was
      2.4% in the Northeastern Region and 8.6% in the Northern Region. CONCLUSION: This
      information before the start of treatment may contribute to clinical decision
      making, reducing treatment failure and the risk of progression to cirrhosis and
      hepatocellular carcinoma for CHB.

PMID- 28740411
TI  - Subgroup analysis of telehealthcare for patients with chronic obstructive
      pulmonary disease: the cluster-randomized Danish Telecare North Trial.
AB  - PURPOSE: Results from the Danish cluster-randomized trial of telehealthcare to
      1,225 patients with chronic obstructive pulmonary disease (COPD), the Danish
      Telecare North Trial, concluded that the telehealthcare solution was unlikely to
      be cost-effective, by applying international willingness-to-pay threshold values.
      The purpose of this article was to assess potential sources of variation across
      subgroups, which could explain overall cost-effectiveness results or be utilized
      in future economic studies in telehealthcare research. METHODS: First, the cost
      structures and cost-effectiveness across COPD severities were analyzed. Second,
      five additional subgroup analyses were conducted, focusing on differences in cost
      effectiveness across a set of comorbidities, age-groups, genders, resource
      patterns (resource use in the social care sector prior to randomization), and
      delivery sites. All subgroups were investigated post hoc. In analyzing cost
      effectiveness, two separate linear mixed-effects models with treatment-by
      covariate interactions were applied: one for quality-adjusted life-year (QALY)
      gain and one for total healthcare and social sector costs. Probabilistic
      sensitivity analysis was used for each subgroup result in order to quantify the
      uncertainty around the cost-effectiveness results. RESULTS: The study concludes
      that, across the COPD severities, patients with severe COPD (GOLD 3
      classification) are likely to be the most cost-effective group. This is primarily
      due to lower hospital-admission and primary-care costs. Telehealthcare for
      patients younger than 60 years is also more likely to be cost-effective than for
      older COPD patients. Overall, results indicate that existing resource patterns of
      patients and variations in delivery-site practices might have a strong influence
      on cost-effectiveness, possibly stronger than the included health or
      sociodemographic sources of heterogeneity. CONCLUSION: Future research should
      focus more on sources of heterogeneity found in the implementation context and
      the way telehealthcare is adopted (eg, by integrating formative evaluation into
      cost-effectiveness analyses). TRIAL REGISTRATION: Clinicaltrials.gov,
      NCT01984840.

PMID- 28740412
TI  - Prevalence of diabetes and obesity in association with prematurity and growth
      restriction.
AB  - Intrauterine growth restriction (IUGR) is when fetuses and newborn infants have
      not reached their true growth potential as genetically defined. Fetuses with IUGR
      develop in a less than ideal environment that leads to epigenetic changes and
      marks infants' metabolism for the rest of their lives. Epigenetic changes affect
      insulin-like growth factor-1 (IGF-1) levels and lead to insulin resistance and
      ultimately to a metabolic syndrome. The metabolic syndrome is a constellation of
      illnesses that raise one's risk for type 2 diabetes mellitus, coronary artery
      disease, and ischemic heart disease, including hypertension, dyslipidemia,
      central obesity, insulin resistance, and inflammation. The association between
      IUGR or prematurity and long-term insulin resistance, obesity, hypertension, and
      metabolic syndrome remains unclear. While studies have shown an association,
      others have not supported such association. If alteration of intrauterine growth
      can ultimately lead to the development of metabolic derangements in childhood and
      adulthood, and if such association is true, then early interventions targeting
      the health of pregnant women will ensure the health of the population to follow.

PMID- 28740413
TI  - Dose-ranging pilot randomized trial of amino acid mixture combined with physical
      activity promotion for reducing abdominal fat in overweight adults.
AB  - OBJECTIVE: The objective of this study was to determine the effective dose of an
      amino acid mixture comprising arginine, alanine, and phenylalanine combined with
      physical activity promotion in reducing abdominal fat among overweight adults.
      METHODS: A 12-week randomized, double-blind, placebo-controlled, dose-ranging,
      pilot trial was conducted in Mito, Japan, from January through April 2016, and
      the data were analyzed from May through November 2016. The study participants
      were 35 overweight adults, aged 20-64 years, with no regular exercise habit.
      Participants were randomly assigned to high-dose (3,000 mg/d, n=9), medium-dose
      (1,500 mg/d, n=9), low-dose (750 mg/d, n=8), or placebo (0 mg/d, n=9) groups, and
      the test beverage containing the amino acid mixture or placebo was administered
      for 12 weeks. All participants maintained a physically active lifestyle during
      the study period through monthly physical activity promotion sessions and
      smartphone-based self-monitoring with wearable trackers. Primary outcomes were
      changes in abdominal total, subcutaneous, and visceral fat areas, assessed by
      computed tomography. RESULTS: Of the 35 enrolled participants, 32 completed the
      12-week follow-up visit. The intention-to-treat analysis revealed that the
      changes in abdominal total fat area were -14.6 cm2 (95% confidence interval [CI],
      -39.6 cm2 to 10.4 cm2), -25.3 cm2 (95% CI, -71.0 cm2 to 20.3 cm2), -23.2 cm2 (95%
      CI, -48.0 cm2 to 1.6 cm2), and -12.5 cm2 (95% CI, -29.1 cm2 to 4.0 cm2) in the
      high-dose, medium-dose, low-dose, and placebo groups, respectively. Similar
      results were obtained for visceral and subcutaneous fat areas. No study-related
      adverse events were reported. CONCLUSION: Compared with placebo, a medium or low
      dose of the amino acid mixture may facilitate abdominal fat reduction among
      overweight adults. A larger randomized trial with sufficient statistical power
      should be implemented to validate the effectiveness of this supplement.

PMID- 28740414
TI  - The role of endoscopic therapy in obesity management: intragastric balloons and
      aspiration therapy.
AB  - Weight management is increasingly incorporating endoscopic bariatric therapy
      (EBT). As the global burden of obesity and its comorbidities has increased, it is
      evident that novel therapeutic approaches will be necessary to address the
      obesity epidemic. EBTs offer greater efficacy than diet and lifestyle
      modification and lower invasiveness than bariatric surgery. The US Food and Drug
      Administration has approved two intragastric balloons and aspiration therapy for
      the treatment of obesity: Apollo Orbera is indicated for the treatment of Class I
      and Class II obesity, Re Shape Integrated Dual Balloon system is indicated for
      the same range with a comorbidity, and Aspire Bariatrics AspireAssist is approved
      for patients with a body mass index of 35-55 kg/m2. These devices have proven
      safe and effective in clinical trials and are gaining commercial acceptance in
      the USA; the Orbera has been used extensively outside the USA for over 20 years.
      These devices will need to be delivered in the context of a multidisciplinary
      weight loss program, integrating comprehensive care of obesity. Patient selection
      is important, and ensuring appropriate patient expectations and understanding of
      alternatives such as pharmacologic therapy and surgery is essential. With several
      EBTs on the horizon, patients with obesity will have an even broader array of
      safe and effective options for weight management in the future.

PMID- 28740415
TI  - The extracellular matrix of eggshell displays anti-inflammatory activities
      through NF-kappaB in LPS-triggered human immune cells.
AB  - Avian eggshell membrane (ESM) is a natural biomaterial that has been used as an
      alternative natural bandage on burned and cut skin injuries for >400 years in
      Asian countries, and is available in large quantities from egg industries. Our
      aim was to characterize ESM that was separated and processed from egg waste, and
      to study whether this material possesses anti-inflammatory properties, making it
      suitable as an ingredient in industrial production of low cost wound healing
      products. Our results show that the processed ESM particles retain a fibrous
      structure similar to that observed for the native membrane, and contain collagen,
      and carbohydrate components such as hyaluronic acid and sulfated
      glycosaminoglycans, as well as N-glycans, mostly with uncharged structures.
      Furthermore, both processed ESM powder and the ESM-derived carbohydrate fraction
      had immunomodulation properties in monocytes and macrophage-like cells. Under
      inflammatory conditions induced by lipopolysaccharide, the ESM powder and the
      isolated carbohydrate fraction reduced the activity of the transcription factor
      nuclear factor-kappaB. The expression of the immune regulating receptors toll
      like receptor 4 and ICAM-1, as well as the cell surface glycoprotein CD44, all
      important during inflammation response, were down-regulated by these fractions.
      Interestingly, our experiments show that the two fractions regulated cytokine
      secretion differently: ESM depressed inflammation by increased secretion of the
      anti-inflammatory cytokine IL-10 while the carbohydrate fraction reduced
      secretions of the pro inflammatory cytokines IL-1beta and IL-6. Also, the
      phosphorylation of p65 and p50 subunits of nuclear factor-kappaB, as well as
      nuclear localization, differed between processed ESM powder and carbohydrate
      fraction, suggesting different down-stream regulation during inflammation. In
      conclusion, processed ESM powder and its soluble carbohydrate components possess
      anti-inflammatory properties, demonstrating the potential of ESM as a novel
      biological wound dressing for treatment of chronic inflammatory wounds.

PMID- 28740416
TI  - Determinants and prevalence of depression in patients with chronic renal disease,
      and their caregivers.
AB  - INTRODUCTION: This study explored the prevalence of depression among the patients
      with chronic kidney disease and their caregivers and its association to their
      demographic profile. METHODS: A descriptive, correlational, cross-sectional study
      that used the Hamilton rating scale tool to assess the prevalence of depression
      among 226 patients undergoing hemodialysis and 105 of their caregivers in a
      hospital in Saudi Arabia. RESULTS: Patients with chronic renal disease and their
      caregivers experience depression at varying levels. Depression was positively
      associated with the socioeconomic and marital status of the patients.
      Socioeconomic status of the caregivers was seen to be associated with their
      depression. CONCLUSION: Depression is highly prevalent among patients with
      chronic renal disease and their caregivers.

PMID- 28740417
TI  - Efficacy and safety of 0.75% ropivacaine instillation into subinguinal wound in
      patients after bilateral microsurgical varicocelectomy: a bi-center, randomized,
      double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of 0.75% ropivacaine instillation
      into inguinal wound in patients who have undergone bilateral microsurgical
      varicocelectomy. PATIENTS AND METHODS: Eighty-five men who were screened for
      bilateral varicoceles from March 2015 to July 2016 were randomized for the
      treatment. All patients underwent inguinal varicocelectomy by general anesthesia.
      After ligation of the internal spermatic veins from the spermatic cord,
      additional delivery of testis through inguinal incision site was done to ligate
      external spermatic veins and gubernacular veins. Before repairing external
      oblique aponeurosis, 6 mL of 0.75% ropivacaine and 6 mL of normal saline were
      instilled under the fascia and around the funiculus (spermatic cord) by a
      randomized and double-blind method. Visual analog scale (VAS) pain score and
      Prince Henry Pain Score (PHPS) were used for evaluating operative sites at 1, 2,
      4, and 8 hours and 7 days after surgery. Safety and tolerability were evaluated
      throughout the course of this study by assessing adverse events. RESULTS: A total
      of 55 men completed the study. Of these 55 men, 31 received instillation of
      ropivacaine on the left operative site, while 24 received instillation of
      ropivacaine on the right operative site. VAS pain scores and PHPS in the
      ropivacaine-instilled operative site were significantly lower compared to those
      obtained with placebo at 2, 4, and 8 hours after surgery. In general,
      instillation of ropivacaine was safe and well tolerated in patients. CONCLUSION:
      Ropivacaine instillation into inguinal surgical site wound significantly reduced
      postoperative pain after microsurgical varicocelectomy.

PMID- 28740418
TI  - Comparison of patient-controlled intravenous analgesia with sufentanil versus
      tramadol in post-cesarean section pain management and lactation after general
      anesthesia - a prospective, randomized, double-blind, controlled study.
AB  - INTRODUCTION: Acute pain is a common complication following cesarean section
      under general anesthesia. Post-cesarean section pain management is important for
      both the mother and the newborn. This study compared the effects of patient
      controlled intravenous analgesia (PCIA) using sufentanil or tramadol on
      postoperative pain control and initiation time of lactation in patients who
      underwent cesarean section under general anesthesia. METHODS: Primiparas (n=146)
      scheduled for cesarean section under general anesthesia were randomized to
      receive PCIA with sufentanil or tramadol. Movement-evoked and rest-pain intensity
      were assessed by the Numerical Rating Scale (NRS) postoperatively. The number of
      PCIA attempts, amount of drug consumed, initiation time of lactation, and Quality
      of Recovery Score 40 (QoR-40) were recorded at 4, 8, 12, and 24 h
      postoperatively. Pre- and postoperative serum prolactin levels were recorded.
      RESULTS: No between-group difference existed in the NRS at rest at any time point
      postoperatively. Patients on sufentanil had more movement-evoked pain and a
      higher sedation score at 4, 8, and 12 h postoperatively, as compared with the
      tramadol group. At 24 h, the QoR-40 was higher in the tramadol group compared
      with the sufentanil group. No significant between-group differences were present
      in patient satisfaction and nausea/vomiting scores. Postpartum prolactin levels
      were significantly higher in the tramadol group versus the sufentanil group,
      corresponding with a significant delay in initiation of lactation in the latter.
      CONCLUSION: PCIA with tramadol may be preferred due to lower movement-evoked
      pain, higher quality of recovery, and earlier lactation in patients following
      cesarean section under general anesthesia.

PMID- 28740419
TI  - Perineural versus intravenous dexamethasone as an adjuvant in regional
      anesthesia: a systematic review and meta-analysis.
AB  - BACKGROUND: Dexamethasone is a common adjuvant for local anesthetics in regional
      anesthesia, but the optimal route of administration is controversial. Therefore,
      we did a systematic review and meta-analysis of randomized controlled trials to
      assess the effect of perineural versus intravenous dexamethasone on local
      anesthetic regional nerve-blockade outcomes. MATERIALS AND METHODS: Medline
      (through PubMed), Embase, Cochrane, Web of Science, and Biosis Previews databases
      were systematically searched (published from inception of each database to
      January 1, 2017) to identify randomized controlled trials. The data of the
      selected trials were statistically analyzed to find any significant differences
      between the two modalities. The primary outcome was the duration of analgesia.
      Secondary outcomes included duration of motor block, postoperative nausea and
      vomiting, and postoperative analgesic dose at 24 hours. We conducted a planned
      subgroup analysis to compare the effects between adding epinephrine or not.
      RESULTS: Ten randomized controlled trials met the inclusion criteria of our
      analysis, with a total of 749 patients. Without the addition of epinephrine, the
      effects of perineural and intravenous dexamethasone were equivalent concerning
      the duration of analgesia (mean difference 0.03 hours, 95% CI -0.17 to 0.24).
      However, with the addition of epinephrine, the analgesic duration of perineural
      dexamethasone versus intravenous dexamethasone was prolonged (mean difference
      3.96 hours, 95% CI 2.66-5.27). Likewise, the impact of epinephrine was the same
      on the duration of motor block. The two routes of administration did not show any
      significant differences in the incidence of postoperative nausea and vomiting,
      nor on postoperative analgesic consumption at 24 hours. CONCLUSION: Our results
      show that perineural dexamethasone can prolong the effects of analgesic duration
      when compared to the intravenous route, only when epinephrine is coadministered.
      Without epinephrine, the two modalities show equivalent effect as adjuvants on
      regional anesthesia.

PMID- 28740420
TI  - A cross-cultural perspective of medical clowning: comparison of its effectiveness
      in reducing pain and anxiety among hospitalized Bedouin and Jewish Israeli
      children.
AB  - PURPOSE: Medical clowning has proven effective for reducing pain, anxiety, and
      stress, however, its differential effects on children from different cultures
      have not yet been researched. This study evaluated the effects of medical
      clowning intervention on anxiety and pain among Jewish and Bedouin children, and
      anxiety among their parents, in southern Israel. PATIENTS AND METHODS: The study
      was conducted in hospital pediatric departments and employed a pre-post design
      involving quantitative and qualitative methods. The study included 89 children
      whose ages ranged from 7.5 to 12 years (39 Jewish and 50 Bedouin) and 69 parents
      (19 Jewish and 50 Bedouin). Questionnaires assessing pain, anxiety, and
      demographics were used at the pre-intervention stage and pain, anxiety, and
      enjoyment of different aspects of the intervention were evaluated following the
      intervention. The intervention stage lasted for 8-10 minutes and included the use
      of word play, body language, and making faces, as well as the use of props
      brought by the clown. Semi-structured interviews were also conducted at the post
      intervention stage. RESULTS: The intervention reduced pain and anxiety among both
      groups of children and reduced anxiety among both groups of parents. However,
      anxiety levels were reduced more significantly among Bedouin children. The
      nonverbal components of the clowns' humor were most central, but it was the
      verbal components that mediated the reduction in anxiety among the Bedouin
      children. CONCLUSION: This study underscored the effectiveness and importance of
      medical clowning in reducing pain and anxiety among children in different
      cultural contexts. Moreover, the issue of culturally appropriate humor was
      underscored and implications for intercultural clown training are discussed.

PMID- 28740421
TI  - Renal colic and childbirth pain: female experience versus male perception.

PMID- 28740422
TI  - Preoperative intravenous ibuprofen does not influence postoperative narcotic use
      in patients undergoing elective hernia repair: a randomized, double-blind,
      placebo controlled prospective trial.
AB  - INTRODUCTION: Inguinal and umbilical hernia repairs are among the most common
      surgical procedures performed in the US. Optimal perioperative pain control
      regimens remain challenging and opioid analgesics are commonly used. Preoperative
      nonsteroidal anti-inflammatory drug (NSAID) administration has been shown to
      reduce postoperative narcotic requirements. This study sought to evaluate the
      efficacy of perioperative intravenous (IV) ibuprofen on postoperative pain level
      and narcotic use in patients undergoing open or laparoscopic inguinal and/or
      umbilical hernia repair. METHODS: A single center, randomized, double-blind
      placebo-controlled trial involving patients >=18 years undergoing inguinal and/or
      umbilical hernia repair was performed. Patients were randomized to receive 800 mg
      of IV ibuprofen or placebo preoperatively. Outcomes assessed included
      postoperative pain medication required and visual analog scale (VAS) pain scores.
      RESULTS: Forty-eight adult male patients underwent inguinal and/or umbilical
      hernia repair. Patients receiving IV ibuprofen used more oxycodone/acetaminophen
      (32% vs 13%) and IV hydromorphone (12% vs 8.7%), and fewer combinations of pain
      medications (44% vs 65.2%) in the first two postoperative hours compared to
      placebo (p=0.556). The IV ibuprofen group had more patients pain free (28% vs
      8.7%, p=0.087) and lower VAS scores (3.08+/-2.14 vs 3.95+/-1.54, p=0.134) at 2
      hours postoperatively, compared to the placebo group, however, this was not
      statistically significant. Similar pain levels at 1, 3, and 7 days, postoperative
      and similar use of rescue medications in both groups were observed. CONCLUSION:
      Preoperative administration of IV ibuprofen did not significantly reduce
      postoperative pain among patients undergoing elective hernia repair. Considerable
      variability in postoperative narcotic analgesic requirement was noted, and larger
      scale studies are needed to better understand the narcotic analgesic requirements
      associated with IV ibuprofen in inguinal/umbilical hernia repair patients.

PMID- 28740423
TI  - Antinociceptive tolerance to NSAIDs in the agranular insular cortex is mediated
      by opioid mechanism.
AB  - Several lines of investigations have shown that in some brain areas, in
      particular, in the midbrain periaqueductal gray matter, rostral ventromedial
      medulla, central nucleus of amygdala, nucleus raphe magnus, and dorsal
      hippocampus, microinjections of nonsteroidal anti-inflammatory drugs (NSAIDs)
      induce antinociception with distinct development of tolerance. The agranular
      insular cortex (AIC) is a small region of the cerebral cortex located on the
      lateral area of the rat's cerebral hemisphere that is involved in the perception
      and response to pain. In the present study, we investigated the development of
      tolerance to the analgesic effects of NSAIDs diclofenac, ketorolac, and xefocam
      microinjected into the AIC in rats. Male Wistar rats receiving NSAIDs into the
      AIC were tested for antinociception by tail-flick and hot plate tests. Treatment
      with each NSAID significantly enhanced the tail-flick and hot plate latencies on
      the first day, followed by a progressive decrease in the analgesic effect over a
      4-day period, ie, they developed tolerance. Pretreatment with an opioid
      antagonist naloxone completely prevented, and posttreatment naloxone abolished,
      the analgesic effects of the three NSAIDs in both behavioral assays. These
      findings support the notion that the development of tolerance to the
      antinociceptive effects of NSAIDs is mediated via an endogenous opioid system
      possibly involving descending pain modulatory systems.

PMID- 28740424
TI  - Risk and protective factors in the clinical rehabilitation of chronic back pain.
AB  - OBJECTIVES: Chronic back pain (CBP) can lead to disability and burden. In
      addition to its medical causes, its development is influenced by psychosocial
      risk factors, the so-called flag factors, which are categorized and integrated
      into many treatment guidelines. Currently, most studies investigate single flag
      factors, which limit the estimation of individual factor significance in the
      development of chronic pain. Furthermore, factors concerning patients' lifestyle,
      biography and treatment history are often neglected. Therefore, the objectives of
      the present study are to identify commonly neglected factors of CBP and integrate
      them into an analysis model comparing their significance with established flag
      factors. METHODS: A total of 24 patients and therapists were cross-sectionally
      interviewed to identify commonly neglected factors of CBP. Subsequently, the
      impact of these factors was surveyed in a longitudinal study. In two
      rehabilitation clinics, CBP patients (n = 145) were examined before and 6 months
      after a 3-week inpatient rehabilitation. Outcome variables, chronification factor
      pain experience (CF-PE) and chronification factor disability (CF-D), were
      ascertained with confirmatory factor analysis (CFA) of standardized
      questionnaires. Predictors were evaluated using stepwise calculations of simple
      and multiple regression models. RESULTS: Through interviews, medical history,
      iatrogenic factors, poor compliance, critical life events (LEs), social support
      (SS) type and effort-reward were identified as commonly neglected factors.
      However, only the final three held significance in comparison to established
      factors such as depression and pain-related cognitions. Longitudinally, lifestyle
      factors found to influence future pain were initial pain, physically demanding
      work, nicotine consumption, gender and rehabilitation clinic. LEs were
      unexpectedly found to be a strong predictor of future pain, as were the
      protective factors, reward at work and perceived SS. DISCUSSION: These findings
      shed insight regarding often overlooked factors in the development of CBP,
      suggesting that more detailed operationalization and superordinate frameworks
      would be beneficial to further research. CONCLUSION: In particular, LEs should be
      taken into account in future research. Protective factors should be integrated in
      therapeutic settings.

PMID- 28740425
TI  - Efficacy of piroxicam for postoperative pain after lower third molar surgery
      associated with CYP2C8*3 and CYP2C9.
AB  - OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are metabolized by the
      cytochrome P450 enzymes (CYPs), predominantly CYP2C8 and CYP2C9. The aim of this
      study was to evaluate the possible association of polymorphisms in the CYP2C8*3
      and CYP2C9 genes with the clinical efficacy of oral piroxicam (20 mg daily for 4
      days) after lower third molar surgeries with regard to postoperative pain,
      swelling, trismus, adverse reactions, need for rescue medication and the
      volunteer's overall satisfaction. MATERIALS AND METHODS: For this purpose, 102
      volunteers were genotyped for CYP2C8*3 and CYP2C9 polymorphisms. Briefly, genomic
      DNA was isolated from saliva collected from volunteers subjected to invasive
      lower third molar surgeries, and the preoperative, intraoperative and
      postoperative parameters were collected and analyzed. RESULTS: An equal amount of
      piroxicam sufficiently managed postoperative pain and inflammatory symptoms, with
      visual analog pain scores typically <40 mm for all genotypes investigated.
      Furthermore, only two out of 102 volunteers heterozygous for CYP2C8*3 and
      CYP2C9*3 reported adverse side effects. CONCLUSION: In general, slow metabolizers
      of piroxicam, who were volunteers with mutant alleles, were indifferent from
      normal metabolizers with the wild-type alleles and therefore did not require
      specialized piroxicam doses to manage postoperative pain and inflammation.

PMID- 28740426
TI  - Efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with
      sore throat due to upper respiratory tract infection: a randomized, non
      inferiority trial in the Russian Federation.
AB  - OBJECTIVE: To assess the efficacy of flurbiprofen 8.75 mg delivered as a spray or
      lozenge in patients with sore throat due to upper respiratory tract infection
      (URTI). MATERIALS AND METHODS: This multicenter, double-blind, double-dummy, non
      inferiority study randomized 440 adults with recent-onset, moderate-to-severe
      sore throat due to URTI to a single dose of either flurbiprofen 8.75 mg spray
      (n=218) or flurbiprofen 8.75 mg lozenge (n=222). The presence or absence of beta
      hemolytic streptococci (A or C) was confirmed by culture tests (throat swab). The
      primary efficacy end point was the difference from baseline to 2 hours post-dose
      in sore throat pain intensity scale (STPIS pain intensity difference [PID] 2h), a
      validated 100 mm visual analog scale (from 0="no pain" to 100="severe pain"),
      with a non-inferiority margin of -6 mm. Secondary end points included STPIS PID
      at 1 hour (STPIS PID 1h) and over 2 hours (STPIS sum of sore throat pain
      intensity differences [SPID]0-2h) and ratings of patient satisfaction and
      investigator assessment of drug efficacy at 2 hours. Safety (adverse events
      [AEs]) was also assessed. RESULTS: Reductions in sore throat pain intensity at 2
      hours (STPIS PID 2h) were similar for spray (least square mean -40.51) and
      lozenge (-40.10) (difference: 0.41, 95% confidence interval [95% CI] -3.20,
      4.01), with non-inferiority demonstrated. Subgroup analyses showed similar
      efficacy (STPIS PID 2h) for patients testing positive or negative for Strep A or
      C. There was no significant difference between spray and lozenge in STPIS PID 1h
      or STPIS SPID0-2h, and patient satisfaction and investigators' assessment of
      efficacy at 2 hours were similar for both groups. There were no significant
      differences in AEs between the two groups, with 17 drug-related events across
      both groups, all being mild and none being serious. CONCLUSION: Both formulations
      demonstrated comparable efficacy and safety profiles and provide patients with
      two different treatment formats to choose from for effective symptomatic relief
      of sore throat, depending on their preference.

PMID- 28740427
TI  - Vulvodynia is not created equally: empirical classification of women with
      vulvodynia.
AB  - BACKGROUND: Vulvodynia classification is based on the sensory dimensions of pain
      and does not include psychological factors associated with the pain experience
      and treatment outcomes. Previous work has shown that individuals with chronic
      pain can be classified into subgroups based on pain sensitivity, psychological
      distress, mood, and symptom severity. OBJECTIVE: The aim of this study was to
      identify distinct subgroups of women with vulvodynia enrolled in the National
      Vulvodynia Registry. We hypothesized that women with vulvodynia can be clustered
      into subgroups based on distress and pain sensitivity. DESIGN: A cross-sectional
      study. METHODS: We conducted an exploratory hierarchical agglomerative cluster
      analysis using Ward's cluster method and squared Euclidean distances to identify
      unique subgroups based on baseline psychological distress and pain sensitivity.
      The variables included the catastrophizing subscale of the Coping Strategies
      Questionnaire, the Beck Depression Inventory, the State Trait Anxiety Index-Trait
      scale, McGill Pain Questionnaire-Affective subscale, and vulvar and pelvic muscle
      pressure pain sensitivity. SUBJECTS: Eight sites enrolled women who presented
      with vaginal or vulval pain of at least 3-month duration. RESULTS: Two distinct
      subgroups, high pain sensitivity with high distress (n=27) and low pain
      sensitivity with low distress (n=100), emerged from the cluster analysis.
      Validation indicated that subgroups differed in terms of clinical pain intensity,
      sensory aspects of pain, and intercourse pain. CONCLUSION: Empirical
      classification indicates that unique subgroups exist in women with vulvodynia.
      Providers should be aware of the heterogeneity of this condition with respect to
      pain-related distress and pain sensitivity.

PMID- 28740428
TI  - Does the approach influence the success rate for ultrasound-guided rectus sheath
      blocks? An anatomical case series.
AB  - The anterior cutaneous branches of the thoracolumbar spinal nerves enter the
      rectus sheath at its lateral border and perforate the muscle after travelling a
      short distance in the ventral direction. In this anatomical case series, we show
      that dye injection at the medial margin did not lead to reliable impregnation of
      the target nerves. The local anesthetic should therefore be injected at the
      lateral edge of the rectus sheath. Preceding surgical procedures to the ventral
      abdominal wall may affect the craniocaudal spread of local anesthetic.

PMID- 28740429
TI  - Comparative diagnostic accuracy of 18F-FDG PET/CT for breast cancer recurrence.
AB  - In the last decades, in addition to conventional imaging techniques and magnetic
      resonance imaging (MRI), 18F-fluorodeoxyglucose positron emission
      tomography/computed tomography (FDG PET/CT) has been shown to be relevant in the
      detection and management of breast cancer recurrence in doubtful cases in
      selected groups of patients. While there are no conclusive data indicating that
      imaging tests, including FDG PET/CT, produce a survival benefit in asymptomatic
      patients, FDG PET/CT can be useful for identifying the site of relapse when
      traditional imaging methods are equivocal or conflicting and for identifying or
      confirming isolated loco-regional relapse or isolated metastatic lesions. The
      present narrative review deals with the potential role of FDG PET in these
      clinical settings by comparing its accuracy and impact with conventional imaging
      modalities such as CT, ultrasound, bone scan, 18F-sodium fluoride PET/CT (18F-NaF
      PET/CT) as well as MRI. Patient-focused perspectives in terms of patients'
      satisfaction and acceptability are also discussed.

PMID- 28740430
TI  - A systematic literature review exploring the prevalence of post-traumatic stress
      disorder and the role played by stress and traumatic stress in breast cancer
      diagnosis and trajectory.
AB  - Stress has been extensively studied as a psychosomatic factor associated with
      breast cancer. This study aims to review the prevalence of post-traumatic stress
      disorder (PTSD), its associated risk factors, the role of predicting factors for
      its early diagnosis/prevention, the implications for co-treatment, and the
      potential links by which stress could impact cancer risk, by closely examining
      the literature on breast cancer survivors. The authors systematically reviewed
      studies published from 2002 to 2016 pertaining to PTSD, breast cancer and PTSD,
      and breast cancer and stress. The prevalence of PTSD varies between 0% and 32.3%
      mainly as regards the disease phase, the stage of disease, and the instruments
      adopted to detect prevalence. Higher percentages were observed when the Clinician
      Administered PTSD Scale was administered. In regard to PTSD-associated risk
      factors, no consensus has been reached to date; younger age, geographic
      provenance with higher prevalence in the Middle East, and the presence of
      previous cancer diagnosis in the family or relational background emerged as the
      only variables that were unanimously found to be associated with higher PTSD
      prevalence. Type C personality can be considered a risk factor, together with low
      social support. In light of the impact of PTSD on cognitive, social, work
      related, and physical functioning, co-treatment of cancer and PTSD is warranted
      and a multidisciplinary perspective including specific training for health care
      professionals in communication and relational issues with PTSD patients is
      mandatory. However, even though a significant correlation was found between
      stressful life events and breast cancer incidence, an unequivocal implication of
      distress in breast cancer is hard to demonstrate. For the future, overcoming the
      methodological heterogeneity represents one main focus. Efficacy studies could
      help when evaluating the effect of co-treating breast cancer and post-traumatic
      stress symptoms, even if all the criteria for a Diagnostic and Statistical Manual
      of Mental Disorders diagnosis are not fulfilled.

PMID- 28740431
TI  - What we know about surgical therapy in early-stage non-small-cell lung cancer: a
      guide for the medical oncologist.
AB  - Lung cancer remains the leading cause of death in cancer patients. The gold
      standard for the treatment of early-stage non-small-cell lung cancer is lobectomy
      with mediastinal lymph-node dissection or systematic lymph-node sampling. The
      evidence behind this recommendation is based on the sole randomized controlled
      trial conducted to date, done by the Lung Cancer Study Group and published in
      1995, which found a superiority for lobectomy over sublobar resection with regard
      to local recurrence rate and improved survival. The population studied at that
      time were medically fit patients at low risk for surgery with a stage IA non
      small-cell lung carcinoma, ie, a solitary tumor less than 3 cm in size. In
      practice, however, thoracic surgeons have continued to push the limit of a more
      conservative surgical resection in this patient population. Since then, several
      retrospective studies have attempted to identify the ideal population to benefit
      from sublobar resection without it affecting survival or local recurrence.
      Several variables have been studied, including tumor size, patient age, surgical
      approach, histological and radiological properties, and optimal surgical
      resection margin, as well as promising prognostic biomarkers. In this review, we
      summarize the data available in the literature regarding the surgical approach to
      patients with stage IA non-small-cell lung cancer studying all the aforementioned
      variables.

PMID- 28740432
TI  - The criterion validity of the web-based Major Depression Inventory when used on
      clinical suspicion of depression in primary care.
AB  - BACKGROUND: The Major Depression Inventory (MDI) is widely used in Danish general
      practice as a screening tool to assess depression in symptomatic patients.
      Nevertheless, no validation studies of the MDI have been performed. The aim of
      this study was to validate the web-based version of the MDI against a fully
      structured telephone interview in a population selected on clinical suspicion of
      depression (ie, presence of two or three core symptoms of depression) in general
      practice. MATERIALS AND METHODS: General practitioners (GPs) invited consecutive
      persons suspected of depression to complete the web-based MDI in a primary care
      setting. The validation was based on the Munich-Composite International
      Diagnostic Interview (M-CIDI) by phone. GPs in the 22 practices in our study
      included 132 persons suspected of depression. Depression was rated as yes/no
      according to the MDI and M-CIDI. Sensitivity, specificity, and positive
      predictive value of the International Classification of Diseases, Tenth Revision
      (ICD-10) algorithms of the MDI were examined. RESULTS: According to the M-CIDI
      interview, 87.9% of the included population was depressed and 64.4% was severely
      depressed. According to the MDI scale, 59.1% of the population was depressed and
      31.8% was severely depressed. The sensitivity of the MDI for depression was 62.1%
      (95% confidence interval [95% CI]: 52.6-70.9) and the specificity was 62.5% (95%
      CI: 35.4-84.8). The sensitivity for severe depression was 42.2% (95% CI: 30.6
      52.4) and the specificity was 85.1% (95% CI: 71.7-93.8). The receiver operating
      curve showed an area under the curve of 0.66 (95% CI: 0.52-0.81) for any
      depression and of 0.72 (95% CI: 0.63-0.81) for severe depression. CONCLUSION: The
      MDI is a conservative instrument for diagnosing ICD-10 depression in a clinical
      setting compared to the M-CIDI interview. Only a few false-positive diagnoses
      were identified when the MDI was used on clinical suspicion of depression.

PMID- 28740433
TI  - Erratum: Validation of second trimester miscarriages and spontaneous deliveries
      [Corrigendum].
AB  - [This corrects the article on p. 517 in vol. 7, PMID: 26715859.].

PMID- 28740434
TI  - A global quantitative survey of hemostatic assessment in postpartum hemorrhage
      and experience with associated bleeding disorders.
AB  - PURPOSE: Coagulopathy may be a serious complicating or contributing factor to
      postpartum hemorrhage (PPH), and should be promptly recognized to ensure proper
      bleeding management. This study aims to evaluate the approaches of obstetrician
      gynecologists worldwide towards assessing massive PPH caused by underlying
      bleeding disorders. METHODS: A quantitative survey was completed by 302
      obstetrician-gynecologists from 6 countries (the UK, France, Germany, Italy,
      Spain, and Japan). The survey included questions on the use of hematologic
      laboratory studies, interpretation of results, laboratory's role in coagulation
      assessments, and experience with bleeding disorders. RESULTS: Overall, the most
      common definitions of "massive" PPH were >2,000 mL (39%) and >1,500 mL (34%)
      blood loss. The most common criteria for rechecking a "stat" complete blood count
      and for performing coagulation studies were a drop in blood pressure (73%) and
      ongoing visible bleeding (78%), respectively. Laboratory coagulation (prothrombin
      time/activated partial thromboplastin time [PT/aPTT]) and factor VIII/IX assays
      were performed on-site more often than were mixing studies (laboratory
      coagulation studies, 93%; factor VIII/IX assays, 63%; mixing studies, 22%). Most
      commonly consulted sources of additional information were colleagues within one's
      own specialty (68%) and other specialists (67%). Most respondents had consulted
      with a hematologist (78%; least, Germany [56%]; greatest, UK [98%]). The most
      common reason for not consulting was hematologist unavailability (44%). The most
      commonly reported thresholds for concern with PT and aPTT were 13 to 20 seconds
      (36%) and 30 to 45 seconds (50%), respectively. Most respondents reported having
      discovered an underlying bleeding disorder (58%; least, Japan [35%]; greatest,
      Spain [74%]). CONCLUSION: Global survey results highlight similarities and
      differences between countries in how PPH is assessed and varying levels of
      obstetrician-gynecologist experience with identification of underlying bleeding
      disorders and engagement of hematology consultants. Opportunities to improve
      patient management of PPH associated with bleeding disorders include greater
      familiarity with interpreting PT/aPTT test results and identification of and
      consistent consultation with hematologists with relevant expertise.

PMID- 28740435
TI  - Barriers and facilitators to cervical cancer screening among Pakistani and Somali
      immigrant women in Oslo: a qualitative study.
AB  - Norway has a low incidence and mortality rate of cervical cancer, which is mainly
      due to the high participation rate of women in cervical cancer screening.
      However, the attendance of cervical cancer screening was reported to be low among
      immigrant women. For this reason, we conducted a qualitative study to obtain
      better insight into perceived barriers and challenges to cervical cancer
      screening among Somali and Pakistani women in the Oslo region. A convenient
      sample of 35 (18 Pakistani, 17 Somali) women were recruited for the study in
      collaboration with Somali and Pakistani community partners. Focus group
      discussions were used to explore barriers and facilitators to cervical cancer
      screening, whereas the Ecological Model was used as the framework for the study.
      The study found three levels of barriers to cervical cancer screening. The
      individual level included a lack of understanding of the benefits of the
      screening. The sociocultural level included the stigma attached to the disease
      and the belief that women who are unmarried are sexually inactive. The system
      related level included a lack of trust toward the health care system. Based on
      the study results, and using a common denominator approach for the immigrant
      groups included, the study recommends three communication strategies with the
      potential to improve women's participation in cervical cancer screening: 1) in
      person communication and information material at health centers; 2) verbal
      communication with women through seminars and workshops to educate them about
      their risk of cancer and the importance of screening and 3) the initiation of
      better recall through SMS and letters written in native languages. Finally, an
      intervention study that compares the aforementioned strategies and proves their
      effectiveness in increasing immigrant women's participation in cervical cancer
      screening is recommended.

PMID- 28740436
TI  - The effect of apatinib in the treatment of metastatic renal cell carcinoma: a
      case report and review of the literature.
AB  - The aim of this study was to explore the effect of apatinib in the treatment of
      metastatic renal cell carcinoma (mRCC) and related adverse events. A case of mRCC
      was reported which recurred after surgery and roferon treatment. The patient was
      treated with apatinib at a dose of 500 mg orally, twice daily, 28 days/cycle. The
      metastatic lesions improved based on computed tomography after apatinib
      administration in the fourth and eighth month. The progression-free survival of
      the patient had increased almost to 8 months. The patient showed a good tolerance
      with only an adverse effect of mild-to-moderate hand-foot syndrome which was
      managed well. Apatinib is an option for mRCC after previous treatment. However,
      more and larger trials are still needed.

PMID- 28740437
TI  - The larynx ruler to measure height and profile of vocal folds: a proof of
      concept.
AB  - INTRODUCTION: Glottic leakage during phonation is a direct consequence of
      unilateral vocal fold (VF) paralysis. This air leakage can be in the horizontal
      plane and in the vertical plane. Presently, there is no easily applicable medical
      device allowing noninvasive, office-based measurement of the relative vertical
      position of the VFs. The larynx ruler (LR) is a laser-based measuring device that
      could meet the previously stated need, using a flexible endoscope. This study
      represents a proof of concept regarding the use of the LR in assessing VF
      relative positions in the vertical plane. MATERIALS AND METHODS: One fresh male
      human cadaver larynx, free of neurologic and anatomic disease, was explored with
      the LR system through the operative channel of a flexible gastroenterology video
      endoscope. The tip of the video-endoscope was located in the laryngeal vestibule.
      The right crico-arytenoid joint was posteriorly disarticulated. Tilting of the VF
      was obtained by pulling or pushing the arytenoid cartilage with a mosquito
      forceps fixed to the stump of the previously sectioned superior tip of the
      posterior crico-arytenoid muscle allowing anterior and posterior tilting of the
      arytenoid cartilage in order to induce an elevation or a depression of the VF
      process. Ten "push" and ten "pull" sessions were performed. The distance from the
      tip of the video-endoscope to each illuminated pixel of the laser beam was
      recorded. The level difference between the left and right VFs was measured for
      each recording. RESULTS: Data provided by the LR were consistently in accordance
      with the movements applied on the VFs. The accuracy of 0.2 mm of the LR is
      compatible with the envisioned applications for the human larynx. CONCLUSION: The
      LR system represents a feasible technique to evaluate respective vertical
      position of VFs in the human larynx. Technical limitations were identified that
      will require improvements before experimental use on human beings.

PMID- 28740438
TI  - Availability and use of hemostatic agents in prehospital trauma patients in
      Pennsylvania translation from the military to the civilian setting.
AB  - OBJECTIVE: To understand the translation of one innovation in trauma care from
      the military to the civilian setting, the adoption of topical hemostatic agents
      in the Emergency Medical Services (EMS) community and in Trauma Centers in
      Pennsylvania. METHOD: We utilized an anonymous electronic survey of EMS Agency
      Administrative Officers and Trauma Center Coordinators. RESULTS: We received
      responses from 23% (93/402) Advanced Life Support and Air Medical agencies in the
      State. Of the EMS agencies that responded, 46.6% (61/131) stock hemostatic
      products, with 55.5% (44/79) carrying QuickClot(r) Combat Gauze(r). Of the
      agencies that carried hemostatic products, 50% utilized them at least once in the
      prior 6 months and 59% over the past 12 months. Despite the infrequent number of
      applications, prehospital providers ranked themselves as somewhat skilled and
      comfortable both with the application of the products and the indications for
      their use. CONCLUSION: Our survey found that 46.6% of the respondents indicated
      they carry hemostatic products, a much greater number than found on prior surveys
      of EMS agencies. There is a steady acceptance by EMS of new innovations in trauma
      care although more work is needed in translating the exact role of hemostatic
      agents in the civilian setting.

PMID- 28740439
TI  - Testing domains of the healing experiences in all life stressors questionnaire in
      a cohort of HIV-infected and HIV-uninfected Chicago women.
AB  - PURPOSE: Patients may deal with issues of spiritual and religious meaning when
      coping with life-threatening or chronic illness. Researchers at the National
      Institutes of Health have developed the healing experiences in all life stressors
      (HEALS) questionnaire, an assessment to determine psychosocial spiritual
      adjustment to healing. Many measures assess religious and spiritual behavior, but
      there exists a need to capture the meaning of these factors in the process of
      healing. The instrument consists of spirituality, religion, interpersonal, and
      intrapersonal domains. This study explores the preliminary partial validation of
      the spirituality and religion domains of the HEALS against the Ironson-Woods
      Spirituality and Religiousness Index (IWSR). METHODS: The abbreviated HEALS,
      IWSR, and a measure of depression were completed by 205 human immunodeficiency
      virus (HIV)-infected and HIV-uninfected women from Chicago as part of the Women's
      Interagency HIV Study. Total scores on the HEALS and IWSR were correlated using
      Pearson correlations to examine convergent validity. Total depression scores were
      analyzed with Pearson correlations to investigate criterion validity. RESULTS:
      Responses between the abbreviated HEALS and IWSR were highly correlated (r=0.74).
      Similar to other measures of its kind, scores on the HEALS were associated with
      depressive symptoms. Women with clinically significant depressive symptoms scored
      significantly lower on the HEALS than women without. No significant differences
      were found for race, age, education, or HIV status. CONCLUSION: This study is an
      important step in the future validation of the HEALS. Results suggest that the
      spirituality and religion domains of the HEALS have good construct validity with
      the IWSR. After further validation, this measure may provide clinicians and
      researchers with a unique way to assess psychosocial spiritual healing.

PMID- 28740440
TI  - HapHop-Physio: a computer game to support cognitive therapies in children.
AB  - BACKGROUND: Care and support of children with physical or mental disabilities are
      accompanied with serious concerns for parents, families, healthcare institutions,
      schools, and their communities. Recent studies and technological innovations have
      demonstrated the feasibility of providing therapy and rehabilitation services to
      children supported by computer games. OBJECTIVE: The aim of this paper is to
      present HapHop-Physio, an innovative computer game that combines exercise with
      fun and learning, developed to support cognitive therapies in children. METHODS:
      Conventional software engineering methods such as the Scrum methodology, a
      functionality test and a related usability test, were part of the comprehensive
      methodology adapted to develop HapHop-Physio. RESULTS: The game supports visual
      and auditory attention therapies, as well as visual and auditory memory
      activities. The game was developed by a multidisciplinary team, which was based
      on the Hopscotch(r) platform provided by Fraunhofer Institute for Digital Media
      Technology IDMT Institute in Germany, and designed in collaboration with a
      rehabilitation clinic in Colombia. HapHop-Physio was tested and evaluated to
      probe its functionality and user satisfaction. CONCLUSION: The results show the
      development of an easy-to-use and funny game by a multidisciplinary team using
      state-of-the-art videogame technologies and software methodologies. Children
      testing the game concluded that they would like to play again while undergoing
      rehabilitation therapies.

PMID- 28740442
TI  - Techniques used for the screening of hemoglobin levels in blood donors: current
      insights and future directions.
AB  - Blood donor hemoglobin (Hb) estimation is an important donation test that is
      performed prior to blood donation. It serves the dual purpose of protecting the
      donors' health against anemia and ensuring good quality of blood components,
      which has an implication on recipients' health. Diverse cutoff criteria have been
      defined world over depending on population characteristics; however, no testing
      methodology and sample requirement have been specified for Hb screening. Besides
      the technique, there are several physiological and methodological factors that
      affect accuracy and reliability of Hb estimation. These include the anatomical
      source of blood sample, posture of the donor, timing of sample and several other
      biological factors. Qualitative copper sulfate gravimetric method has been the
      archaic time-tested method that is still used in resource-constrained settings.
      Portable hemoglobinometers are modern quantitative devices that have been further
      modified to reagent-free cuvettes. Furthermore, noninvasive spectrophotometry was
      introduced, mitigating pain to blood donor and eliminating risk of infection.
      Notwithstanding a tremendous evolution in terms of ease of operation, accuracy,
      mobility, rapidity and cost, a component of inherent variability persists, which
      may partly be attributed to pre-analytical variables. Hence, blood centers should
      pay due attention to validation of test methodology, competency of operating
      staff and regular proficiency testing of the outputs. In this article, we have
      reviewed various regulatory guidelines, described the variables that affect the
      measurements and compared the validated technologies for Hb screening of blood
      donors along with enumeration of their merits and limitations.

PMID- 28740441
TI  - Detection of ROS1 rearrangement in non-small cell lung cancer: current and future
      perspectives.
AB  - ROS1 rearrangement characterizes a small subset (1%-2%) of non-small cell lung
      cancer and is associated with slight/never smoking patients and adenocarcinoma
      histology. Identification of ROS1 rearrangement is mandatory to permit targeted
      therapy with specific inhibitors, demonstrating a significantly better survival
      when compared with conventional chemotherapy. Detection of ROS1 rearrangement is
      based on in situ (immunohistochemistry, fluorescence in situ hybridization) and
      extractive non-in situ assays. While fluorescence in situ hybridization still
      represents the gold standard in clinical trials, this technique may fail to
      recognize rearrangements of ROS1 with some gene fusion partner. On the other
      hand, immunohistochemistry is the most cost-effective screening technique, but it
      seems to be characterized by low specificity. Extractive molecular assays are
      expensive and laborious methods, but they specifically recognize almost all ROS1
      fusions using a limited amount of mRNA even from formalin-fixed, paraffin
      embedded tumor tissues. This review is a discussion on the present and futuristic
      diagnostic scenario of ROS1 identification in lung cancer.

PMID- 28740443
TI  - Approaches to teach evidence-based practice among health professionals: an
      overview of the existing evidence.
AB  - Health care professionals' adoption of evidence-based practice (EBP) remains
      limited, although most health care professionals are familiar with EBP and
      believe in its value. This systematic review aimed to bring together the best
      methods used to teach EBP to health professionals. The authors conducted a
      systematic search for the period 2005-2015 (an update of the search took place in
      October 2016) using PubMed interface (Medline). MeSH terms as well as free-text
      keywords were used. Studies were analyzed and evaluated by title and abstract.
      Those studies which fulfilled the inclusion criteria were assessed by full text.
      References of articles were also taken into consideration for identifying
      relevant studies not found through algorithm search. Twenty articles were found
      to be relevant. The majority of the studies were conducted among nurses (n=7) and
      physicians (n=6), and only a few among professionals from mixed disciplines
      (n=5). Two studies were conducted among chiropractors (n=1) and faculty members
      from a naturopathic and classical Chinese medicine institution (n=1). Researchers
      used a variety of different approaches, which varied with respect to duration and
      organization. We divided interventions into two categories. Single interventions
      included either a workshop, or a journal club, or a conference, or a lecture, or
      online learning tools, whereas multiple interventions included a combination of
      these approaches. An increase in EBP competencies and attitudes was reported in
      nine studies. Teaching methods for optimizing EBP among health professionals
      could become a robust standardized procedure of the medical educational curricula
      and lifelong learning of health care professionals.

PMID- 28740444
TI  - Effective deployment of technology-supported management of chronic respiratory
      conditions: a call for stakeholder engagement.
AB  - BACKGROUND: Healthcare systems are under increasing strain, predominantly due to
      chronic non-communicable diseases. Connected healthcare technologies are becoming
      ever more capable and their components cheaper. These innovations could
      facilitate both self-management and more efficient use of healthcare resources
      for common respiratory diseases such as asthma and chronic obstructive pulmonary
      disease. However, newer technologies can only facilitate major changes in
      practice, and cannot accomplish them in isolation. FOCUS OF REVIEW: There are now
      large numbers of devices and software offerings available. However, the potential
      of such technologies is not being realised due to limited engagement with the
      public, clinicians and providers, and a relative paucity of evidence describing
      elements of best practice in this complex and evolving environment. Indeed, there
      are clear examples of wasted resources and potential harm. We therefore call on
      interested parties to work collaboratively to begin to realize the potential
      benefits and reduce the risks of connected technologies through change in
      practice. We highlight key areas where such partnership can facilitate the
      effective and safe use of technology in chronic respiratory care: developing data
      standards and fostering inter-operability, making collaborative testing
      facilities available at scale for small to medium enterprises, developing and
      promoting new adaptive trial designs, developing robust health economic models,
      agreeing expedited approval pathways, and detailed planning of dissemination to
      use. CONCLUSION: The increasing capability and availability of connected
      technologies in respiratory care offers great opportunities and significant
      risks. A co-ordinated collaborative approach is needed to realize these benefits
      at scale. Using newer technologies to revolutionize practice relies on widespread
      engagement and cannot be delivered by a minority of interested specialists.
      Failure to engage risks a costly and inefficient chapter in respiratory care.

PMID- 28740445
TI  - Resolution of Students t-tests, ANOVA and analysis of variance components from
      intermediary data.
AB  - Significance testing in comparisons is based on Student's t-tests for pairs and
      analysis of variance (ANOVA) for simultaneous comparison of several procedures.
      Access to the average, standard deviation and number of observations is
      sufficient for calculating the significance of differences using the Student's
      tests and the ANOVA. Once an ANOVA has been calculated, analysis of variance
      components from summary data becomes possible. Simple calculations based on
      summary data provide inference on significance testing. Examples are given from
      laboratory management and method comparisons. It is emphasized that the usual
      criteria of the underlying distribution of the raw data must be fulfilled.

PMID- 28740446
TI  - Diffusion Kurtosis Imaging of Gliomas Grades II and III - A Study of Perilesional
      Tumor Infiltration, Tumor Grades and Subtypes at Clinical Presentation.
AB  - BACKGROUND: Diffusion kurtosis imaging (DKI) allows for assessment of diffusion
      influenced by microcellular structures. We analyzed DKI in suspected low-grade
      gliomas prior to histopathological diagnosis. The aim was to investigate if
      diffusion parameters in the perilesional normal-appearing white matter (NAWM)
      differed from contralesional white matter, and to investigate differences between
      glioma malignancy grades II and III and glioma subtypes (astrocytomas and
      oligodendrogliomas). PATIENTS AND METHODS: Forty-eight patients with suspected
      low-grade glioma were prospectively recruited to this institutional review board
      approved study and investigated with preoperative DKI at 3T after written
      informed consent. Patients with histologically proven glioma grades II or III
      were further analyzed (n=35). Regions of interest (ROIs) were delineated on
      T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data
      were compared between perilesional and contralesional NAWM (student's t-test for
      dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared
      between glioma types and glioma grades (multiple comparisons of mean ranks for
      all groups). The discriminating potential for DKI in assessing glioma type and
      grade was assessed with receiver operating characteristics (ROC) curves. RESULTS:
      There were significant differences in all mean DKI variables between perilesional
      and contralesional NAWM (p=<0.000), except for axial kurtosis (p=0.099). Forty
      four histogram variables differed significantly between glioma grades II (n=23)
      and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between
      ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating
      variables had an area under the curve (AUC) of 0.657-0.815. CONCLUSIONS: Mean DKI
      variables in perilesional NAWM differ significantly from contralesional NAWM,
      suggesting altered microstructure by tumor infiltration not depicted on
      morphological MRI. Histogram analysis of DKI data identifies differences between
      glioma grades and subtypes.

PMID- 28740447
TI  - Breast Dynamic Contrast Enhanced MRI: Fibrocystic Changes Presenting as a Non
      mass Enhancement Mimicking Malignancy.
AB  - BACKGROUND: We aimed to analyse the morphokinetic features of breast fibrocystic
      changes (nonproliferative lesions, proliferative lesions without atypia and
      proliferative lesions with atypia) presenting as a non-mass enhancement (NME)in
      dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examination.
      PATIENTS AND METHODS: Forty-six patients with histologically proven fibrocystic
      changes (FCCs) were retrospectively reviewed, according to Breast Imaging
      Reporting and Data System (BI-RADS) lexicon. Prior to DCE-MRI examination, a
      unilateral breast lesion suspicious of malignancy was detected clinically, on
      mammography or breast ultrasonography. RESULTS: The predominant features of FCCs
      presenting as NME in DCE-MRI examination were: unilateral regional or diffuse
      distribution (in 35 patients or 76.1%), heterogeneous or clumped internal pattern
      of enhancement (in 36 patients or 78.3%), plateau time-intensity curve (in 25
      patients or 54.3%), moderate or fast wash-in (in 31 patients or
      67.4%).Nonproliferative lesions were found in 11 patients (24%), proliferative
      lesions without atypia in 29 patients (63%) and lesions with atypia in six
      patients (13%), without statistically significant difference of morphokinetic
      features, except of the association of clustered microcysts with proliferative
      dysplasia without atypia. CONCLUSIONS: FCCs presenting as NME in DCE-MRI
      examination have several morphokinetic features suspicious of malignancy,
      therefore requiring biopsy (BI-RADS 4). Nonproliferative lesions, proliferative
      lesions without atypia and proliferative lesions with atypia predominantly share
      the same predefined DCE-MRI morphokinetic features.

PMID- 28740448
TI  - Evaluation of Brain Edema Formation Defined By MRI After LINAC-based Stereotactic
      Radiosurgery.
AB  - BACKGROUND: Peri-lesional edema is a serious and well-known complication of
      stereotactic radiosurgery (SRS). Here we evaluated edema risk after SRS and
      assessed its formation and resolution dynamics. PATIENTS AND METHODS: 107
      patients underwent SRS for heterogeneous diagnoses: 34 (29%) with arteriovenous
      malformations, 38 (35%) with meningiomas, 16 (15%) with metastatic tumors, 16
      (15%) with acoustic neuromas, 3 with (3%) cavernomas, and 2 (2%) each with
      anaplastic astrocytomas and anaplastic oligoastrocytomas. Edema area was
      delineated in MRI T2-FLAIR sequences 0, 6, 12, 18, 24, 30, and 38 months after
      treatment. Lesion location was defined as either above (n = 80) or below (n = 32)
      the "Frankfurt modified line" (FML). RESULTS: 17% of patients developed or had
      worsening post-treatment edema. Edema volume was maximal at 6 months (mean 7.2,
      SD 1.2) post radiosurgery. Post-SRS edema was 5.1 (1.06 - 24.53) times more
      likely in patients with lesions above the FML. There was no association between
      edema development and age, PTV size, number of beams, and diagnosis (p = 0.07).
      CONCLUSIONS: Radiosurgery-associated edema develops within 6 months of treatment
      and decreases over time. Edema occurrence is strongly related to lesion location,
      and its presence is much more likely when the treated lesions are situated above
      the Frankfurt line.

PMID- 28740449
TI  - Genetic Factors Affecting Intraoperative 5-aminolevulinic Acid-induced
      Fluorescence of Diffuse Gliomas.
AB  - BACKGROUND: In patients operated for malignant glioma, 5-aminolevulinic acid (5
      ALA)-induced fluorescence guidance is useful. However, we occasionally experience
      instances of non-visible fluorescence despite a histopathological diagnosis of
      high-grade glioma. We sought to identify factors that influence the
      intraoperative visualization of gliomas by their 5-ALA-induced fluorescence.
      PATIENTS AND METHODS: We reviewed data from 60 patients with astrocytic or
      oligodendroglial tumors who underwent tumor removal under 5-ALA-induced
      fluorescence guidance between January 2014 and December 2015. Their
      characteristics, preoperative magnetic resonance imaging (MRI) findings,
      histological diagnosis, and genetic profile were analyzed and univariate and
      multivariate statistical analyses were performed. RESULTS: In 42 patients (70%)
      we intraoperatively observed tumor 5-ALA fluorescence. They were 2 of 8 (25%)
      patients with World Health Organization (WHO) grade II, 9 of 17 (53%) with grade
      III, and 31 of 35 (89%) patients with grade IV gliomas. Univariate analysis
      revealed a statistically significant association between 5-ALA fluorescence and
      the isocitrate dehydrogenase 1 (IDH1) status, 1p19q loss of heterozygosity (LOH),
      the MIB-1 labeling index, and the tumor margin, -heterogeneity, and -contrast
      enhancement on MRI scans (p < 0.001, p = 0.003, p = 0.007, p = 0.046, p = 0.021,
      and p = 0.002, respectively). Multivariate analysis showed that the IDH1 status
      was the only independent, statistically significant factor related to 5-ALA
      fluorescence (p = 0.009). CONCLUSIONS: This study identified the IDH1 status as
      the factor with the most influence on the 5-ALA fluorescence of diffuse gliomas.

PMID- 28740450
TI  - Single Nucleotide Polymorphisms in Genes MACC1, RAD18, MMP7 and SDF-1a As
      Prognostic Factors in Resectable Colorectal Cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) represents one of the most common
      malignancies worldwide. Research has indicated that functional gene changes such
      as single nucleotide polymorphism (SNP) influence carcinogenesis and metastasis
      and might have an influence on disease relapse. The aim of our study was to
      evaluate the role of SNPs in selected genes as prognostic markers in resectable
      CRC. PATIENTS AND METHODS: In total, 163 consecutive patients treated surgically
      for CRC of stages I, II and III at the University Medical Centre in Maribor in
      2007 and 2008 were investigated. DNA was isolated from formalin-fixed paraffin
      embedded CRC tissue from the Department of Pathology and SNPs in genes SDF-1a,
      MMP7, RAD18 and MACC1 were genotyped using polymerase chain reaction followed by
      high resolution melting curve analysis or restriction fragment length
      polymorphism. RESULTS: We found worse disease-free survival (DFS) for patients
      with TT genotype of SNP rs1990172 in gene MACC1 (p = 0.029). Next, we found worse
      DFS for patients with GG genotype for SNP rs373572 in gene RAD18 (p = 0.020).
      Higher frequency of genotype GG of MMP7 SNP rs11568818 was found in patients with
      T3/T4 stage (p = 0.014), N1/N2 stage (p = 0.041) and with lymphovascular invasion
      (p = 0.018). For MACC1 rs1990172 SNP we found higher frequency of genotype TT in
      patients with T3/T4 staging (p = 0.024). Higher frequency of genotype GG of RAD18
      rs373572 was also found in patients with T1/T2 stage with disease relapse (p =
      0.041). CONCLUSIONS: Our results indicate the role of SNPs as prognostic factors
      in resectable CRC.

PMID- 28740451
TI  - MRI Reduces Variation of Contouring for Boost Clinical Target Volume in Breast
      Cancer Patients Without Surgical Clips in the Tumour Bed.
AB  - BACKGROUND: Omitting the placement of clips inside tumour bed during breast
      cancer surgery poses a challenge for delineation of lumpectomy cavity clinical
      target volume (CTVLC). We aimed to quantify inter-observer variation and accuracy
      for CT- and MRI-based segmentation of CTVLC in patients without clips. PATIENTS
      AND METHODS: CT- and MRI-simulator images of 12 breast cancer patients, treated
      by breast conserving surgery and radiotherapy, were included in this study. Five
      radiation oncologists recorded the cavity visualization score (CVS) and
      delineated CTVLC on both modalities. Expert-consensus (EC) contours were
      delineated by a senior radiation oncologist, respecting opinions of all
      observers. Inter-observer volumetric variation and generalized conformity index
      (CIgen) were calculated. Deviations from EC contour were quantified by the
      accuracy index (AI) and inter-delineation distances (IDD). RESULTS: Mean CVS was
      3.88 +/- 0.99 and 3.05 +/- 1.07 for MRI and CT, respectively (p = 0.001). Mean
      volumes of CTVLC were similar: 154 +/- 26 cm3 on CT and 152 +/- 19 cm3 on MRI.
      Mean CIgen and AI were superior for MRI when compared with CT (CIgen: 0.74 +/-
      0.07 vs. 0.67 +/- 0.12, p = 0.007; AI: 0.81 +/- 0.04 vs. 0.76 +/- 0.07; p =
      0.004). CIgen and AI increased with increasing CVS. Mean IDD was 3 mm +/- 1.5 mm
      and 3.6 mm +/- 2.3 mm for MRI and CT, respectively (p = 0.017). CONCLUSIONS: When
      compared with CT, MRI improved visualization of post-lumpectomy changes, reduced
      interobserver variation and improved the accuracy of CTVLC contouring in patients
      without clips in the tumour bed. Further studies with bigger sample sizes are
      needed to confirm our findings.

PMID- 28740452
TI  - The Influence of the Distal Resection Margin Length on Local Recurrence and long-
      term Survival in Patients with Rectal Cancer after Chemoradiotherapy and
      Sphincter- Preserving Rectal Resection.
AB  - BACKGROUND: Low recurrence rates and long term survival are the main therapeutic
      goals of rectal cancer surgery. Complete, margin- negative resection confers the
      greatest chance for a cure. The aim of our study was to determine whether the
      length of the distal resection margin was associated with local recurrence rate
      and long- term survival. PATIENTS AND METHODS: One hundred and nine patients, who
      underwent sphincter-preserving resection for locally advanced rectal cancer after
      preoperative chemoradiotherapy between 2006 and 2010 in two tertiary referral
      centres were included in the study. Distal resection margin lengths were measured
      on formalin-fixed, pinned specimens. Characteristics of patients with distal
      resection margin < 8 mm (Group I, n = 27), 8-20 mm (Group II, n = 31) and > 20 mm
      (Group III, n = 51) were retrospectively analysed and compared. Median (range)
      follow-up time in Group I was 89 (51-111), in Group II 83 (57-111) and in Group
      III 80 (45-116) months (p = 0.326), respectively. RESULTS: Univariate survival
      analysis showed that distal resection margin length was not statistically
      significantly associated with overall survival or local recurrence rate (p >
      0.05). In a multiple Cox regression analysis, after adjusting for pathologic T
      and N stage (yT, yN), distal resection margin length was still not statistically
      significantly associated with overall survival. CONCLUSIONS: Our study shows that
      close distal resection margins can be accepted as oncologically safe for
      sphincter-preserving rectal resections after preoperative chemoradiotherapy.

PMID- 28740453
TI  - Clinical Outcomes of 130 Patients with Primary and Secondary Lung Tumors treated
      with Cyberknife Robotic Stereotactic Body Radiotherapy.
AB  - BACKGROUND: Authors report clinical outcomes of patients treated with robotic
      stereotactic body radiotherapy (SBRT) for primary, recurrent and metastatic lung
      lesions. PATIENTS AND METHODS: 130 patients with 160 lesions were treated with
      Cyberknife SBRT, including T1-3 primary lung cancers (54%), recurrent tumors
      (22%) and pulmonary metastases (24%). The mean biologically equivalent dose
      (BED10Gy) was 151 Gy (72-180 Gy). Median prescribed dose for peripheral and
      central lesions was 3*20 Gy and 3*15 Gy, respectively. Local control (LC),
      overall survival (OS), and cause-specific survival (CSS) rates, early and late
      toxicities are reported. Statistical analysis was performed to identify factors
      influencing local tumor control. RESULTS: Median follow-up time was 21 months. In
      univariate analysis, higher dose was associated with better LC and a cut-off
      value was detected at BED10Gy <= 112.5 Gy, resulting in 1-, 2-, and 3-year
      actuarial LC rates of 93%, vs 73%, 80% vs 61%, and 63% vs 54%, for the high and
      low dose groups, respectively (p = 0.0061, HR = 0.384). In multivariate analysis,
      metastatic origin, histological confirmation and larger Planning Target Volume
      (PTV) were associated with higher risk of local failure. Actuarial OS and CSS
      rates at 1, 2, and 3 years were 85%, 74% and 62%, and 93%, 89% and 80%,
      respectively. Acute and late toxicities >= Gr 3 were observed in 3 (2%) and 6
      patients (5%), respectively. CONCLUSIONS: Our favorable LC and survival rates
      after robotic SBRT, with low rates of severe toxicities, are coherent with the
      literature data in this mixed, non-selected study population.

PMID- 28740454
TI  - Genetic Counselling, BRCA1/2 Status and Clinico-pathologic Characteristics of
      Patients with Ovarian Cancer before 50 Years of Age.
AB  - BACKGROUND: In Slovenia like in other countries, till recently, personal history
      of epithelial ovarian cancer (EOC) has not been included among indications for
      genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2
      mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The
      original aim of this study was to invite to the genetic counselling still living
      patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform
      analysis of gBRCA1/2m rate and of clinico-pathologic characteristics. Later, we
      added also the data of previously genetically tested patients with EOC aged 45 to
      49 years. PATIENTS AND METHODS: All clinical data have to be interpreted in the
      light of many changes happened in the field of EOC just in the last few years:
      new hystology stage classification (FIGO), new hystology types and
      differentiation grades classification, new therapeutic possibilities (PARP
      inhibitors available, also in Slovenia) and new guidelines for genetic
      counselling of EOC patients (National Comprehensive Cancer Network, NCCN),
      together with next-generation sequencing possibilities. RESULTS: Compliance rate
      at the invitation was 43.1%. In the group of 27 invited or previously tested
      patients with EOC diagnosed before the age of 45 years, five gBRCA1/2 mutations
      were found. The gBRCA1/2m detection rate within the group was 18.5%. There were 4
      gBRCA1 and 1 gBRCA2 mutations detected. In the extended group of 42 tested
      patients with EOC diagnosed before the age of 50 years, 14 gBRCA1/2 mutations
      were found. The gBRCA1/2m detection rate within this extended, partially selected
      group was 33.3%. There were 11 gBRCA1 and 3 gBRCA2 mutations detected.
      CONCLUSIONS: The rate of gBRCA1/2 mutation in tested unselected EOC patients
      under the age of 50 years was higher than 10%, namely 18.5%. Considering also a
      direct therapeuthic benefit of PARP inhibitors for BRCA positive patients, there
      is a double reason to offer genetic testing to all EOC patients younger than 50
      years. Regarding clinical data, it is important to perform their re
      interpretation in everyday clinical practice, because this may influence
      therapeutic possibilities to be offered.

PMID- 28740455
TI  - Insulin-like Growth Factor 1 Receptor Expression in Advanced Non-small-cell Lung
      Cancer and its Impact on Overall Survival.
AB  - BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) expression has been
      addressed as a potential prognostic marker in non-small-cell lung cancer (NSCLC)
      in various studies; however, the associations between IGF1R expression and
      prognosis of advanced NSCLC patients is still controversial. The aim of our
      observational, cohort study was to evaluate the expression of IGF1R in advanced
      NSCLC and its prognostic role. A subgroup analysis was performed to address the
      influence of pre-existing type 2 diabetes mellitus (T2DM) status on IGF1R
      expression and overall survival (OS). PATIENTS AND METHODS: IGF1R expression was
      evaluated in 167 consecutive advanced NSCLC patients (stage IIIB and IV),
      diagnosed and treated at one university institution, between 2005 and 2010. All
      patients received at least one line of standard cytotoxic therapy and 18 of them
      had pre-existing T2DM. IGF1R expression was determined by immunohistochemical
      (IHC) staining, with score >= 1+ considered as positive. Information on baseline
      characteristics, as well as patients' follow-up data, were obtained from the
      hospital registry. Associations of IGF1R expression with clinical characteristics
      and overall survival were compared. RESULTS: IGF1R expression was positive in
      79.6% of patients, significantly more often in squamous-cell carcinoma (SCC)
      compared to non-squamous-cell (NSCC) histology (88.7% vs. 74.3%; P = 0.03). IGF1R
      positivity did not correlate with T2DM status or with other clinical features
      (sex, smoking status, performance status). Median OS was similar between IGF1R
      positive and IGF1R negative group (10.2 vs. 8.5 months, P = 0.168) and between
      patients with or without T2DM (8.7 vs. 9.8 months, P = 0.575). Neither IGF1R
      expression nor T2DM were significant predictors of OS. CONCLUSIONS: IGF1R or T2DM
      status were not significantly prognostic in described above collective of
      advanced NSCLC treated with at least one line of chemotherapy. In addition, no
      association between T2DM status and IGF1R expression was found. Further studies
      on IGF1R expression and its prognostic as well as therapeutic consequences in a
      larger collective of advanced NSCLC patients, with or without T2DM, are needed.

PMID- 28740456
TI  - Carotid Artery Stiffness, Digital Endothelial Function, and Coronary Calcium in
      Patients with Essential Thrombocytosis, Free of Overt Atherosclerotic Disease.
AB  - BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) are at increased
      risk for atherothrombotic events. Our aim was to determine if patients with
      essential thrombocytosis (ET), a subtype of MPNs, free of symptomatic
      atherosclerosis, have greater carotid artery stiffness, worse endothelial
      function, greater coronary calcium and carotid plaque burden than control
      subjects. PATIENTS AND METHODS: 40 ET patients without overt vascular disease,
      and 42 apparently healthy, age and sex-matched control subjects with comparable
      classical risk factors for atherosclerosis and Framingham risk of coronary
      disease were enrolled. All subjects were examined by physical and laboratory
      testing, carotid echo-tracking ultrasound, digital EndoPat pletysmography and CT
      coronary calcium scoring. RESULTS: No significant differences were found between
      ET patients and controls in carotid plaque score [1 (0-1.25) vs. 0 (0-2),
      p=0.30], beta- index of carotid stiffness [7.75 (2.33) vs. 8.44 (2,81), p=0.23],
      pulse wave velocity [6,21 (1,00) vs. 6.45 (1.04) m/s; p=0.46], digital reactive
      hyperemia index [2.10 (0.57) vs. 2.35 (0.62), p=0.07], or augmentation index [19
      (3-30) vs. 13 (5-22) %, p=0.38]. Overall coronary calcium burden did not differ
      between groups [Agatston score 0.1 (0-16.85) vs. 0 (0-8.55), p=0.26]. However,
      significantly more ET patients had an elevated coronary calcium score of >160
      [6/40 vs. 0/42, p < 0.01]. CONCLUSIONS: No significant differences between groups
      were found in carotid artery morphology and function, digital endothelial
      function or overall coronary calcium score. Significantly more ET patients had an
      elevated coronary calcium score of >160, indicating high cardiovascular risk, not
      predicted by the Framingham equation.

PMID- 28740457
TI  - Perioperative Increase in Neutrophil CD64 Expression is an Indicator for Intra
      abdominal Infection after Colorectal Cancer Surgery.
AB  - BACKGROUND: Colorectal surgery is associated with a high incidence of
      postoperative infections. Early clinical signs are difficult to distinguish from
      the systemic inflammatory response related to surgical trauma. Timely diagnosis
      may significantly improve the outcome. The objective of this study was to compare
      a new biomarker index CD64 for neutrophils (iCD64n) with standard biomarkers,
      white blood cell (WBC) count, neutrophil/lymphocyte ratio (NLR), C-reactive
      protein (CRP) and procalcitonin (PCT) for the early detection of postoperative
      infection. METHODS: The prospective study included 200 consecutive patients with
      elective colorectal cancer surgery. Postoperative values of biomarkers from the
      postoperative day (POD) 1 to POD5 were analysed by the receiver operating
      characteristic (ROC) analysis to predict infection. The Cox regression model and
      the Kaplan-Meier method were used to assess prognostic factors and survival.
      RESULTS: The increase of index CD64n (iCD64n) after surgery, expressed as the
      ratio iCD64n after/before surgery was a better predictor of infection than its
      absolute value. The best 30-day predictors of all infections were CRP on POD4
      (AUC 0.72, 99% CI 0.61-0.83) and NLR on POD5 (AUC 0.69, 99% CI 0.57-0.80). The
      best 15-day predictors of organ/space surgical site infection (SSI) were the
      ratio iCD64n on POD1 (AUC 0.72, 99% CI 0.58-0.86), POD3 (AUC 0.73, 99% CI 0.59
      0.87) and CRP on POD3 (AUC 0.72, 99% CI 0.57-0.86), POD4 (AUC 0.79, 99% CI 0.64
      0.93). In a multivariate analysis independent risk factors for infections were
      duration of surgery and perioperative transfusion while the infection itself was
      identified as a risk factor for a worse long-term survival. CONCLUSIONS: The
      ratio iCD64n on POD1 is the best early predictor of intra-abdominal infection
      after colorectal cancer surgery. CRP predicts the infection with the same
      predictive value on POD3.

PMID- 28740458
TI  - Treatment-related Cardiovascular Toxicity in Long-term Survivors of Testicular
      Cancer.
AB  - BACKGROUNDS: Testicular cancer is the most common malignancy in young men.
      Considering increasing incidence, exceptionally high cure rate, as well as long
      life expectancy, assessment of long term toxicity in testicular cancer survivors
      is of great importance. In the last decades a major effort has been made in order
      to reduce toxicity of treatment, while maintaining its high effectiveness.
      CONCLUSIONS: Actual knowledge on treatment toxicity is based on outdated
      treatment modalities. Hopefully, modern treatment modalities could reduce
      toxicity, but, there is no firm confirmation for that at the moment, as data
      dealing with late sequelae of modern treatment of testicular cancer are not
      available yet due to the short period of observation. The life-threatening
      cardiovascular toxicity in testicular cancer survivors is major complication of
      platinum-based chemotherapy, mediastinal radiotherapy and even subdiaphragmatic
      radiotherapy.

PMID- 28740459
TI  - Dosimetric Predictors of Treatment-related Lymphopenia induced by Palliative
      Radiotherapy: Predictive Ability of Dose-volume Parameters based on Body Surface
      Contour.
AB  - BACKGROUND: Radiation-related lymphopenia has been associated with poor patient
      outcome. Our aim was to identify predictors of lymphopenia after palliative
      radiotherapy, with a focus on dose-volume parameters. PATIENTS AND METHODS: To
      retrospectively assess patients with various cancers who had undergone palliative
      radiotherapy, we delineated three organs at risk: the volume enclosed by the body
      surface contour (body A), the volume left after excluding air, pleural effusion,
      ascites, bile, urine, and intestinal content (body B), and the volume of the bone
      marrow (BM). We then noted the absolute volume of the three organs at risk that
      had received 5-30 Gy, and assessed the predictive value for post-treatment
      lymphopenia of grade 3 or higher (LP3+). RESULTS: Of 54 patients, 23 (43%)
      developed LP3+. Univariate logistic regression analysis showed that body A V5,
      body A V10, body B V5, body B V10, the number of fractions, and splenic
      irradiation were significant predictors of LP3+ (p < 0.05). By multivariate
      analysis, body A V5, body A V10, body B V5, body B V10, and the number of
      fractions retained significance (p < 0.05). BM dose-volume parameters did not
      predict lymphopenia. CONCLUSIONS: Higher body A and body B dose-volume parameters
      and a larger number of fractions may be predictors of severe lymphopenia after
      palliative radiotherapy.

PMID- 28740460
TI  - Excess of Radiation Burden for Young Testicular Cancer Patients using Automatic
      Exposure Control and Contrast Agent on Whole-body Computed Tomography Imaging.
AB  - BACKGROUND: The aim of the study was to assess patient dose from whole-body
      computed tomography (CT) in association with patient size, automatic exposure
      control (AEC) and intravenous (IV) contrast agent. PATIENTS AND METHODS: Sixty
      five testicular cancer patients (mean age 28 years) underwent altogether 279
      whole-body CT scans from April 2000 to April 2011. The mean number of repeated
      examinations was 4.3. The GE LightSpeed 16 equipped with AEC and the Siemens Plus
      4 CT scanners were used for imaging. Whole-body scans were performed with (216)
      and without (63) IV contrast. The ImPACT software was used to determine the
      effective and organ doses. RESULTS: Patient doses were independent (p < 0.41) of
      patient size when the Plus 4 device (mean 7.4 mSv, SD 1.7 mSv) was used, but with
      the LightSpeed 16 AEC device, the dose (mean 14 mSv, SD 4.6 mSv) increased
      significantly (p < 0.001) with waist cirfumference. Imaging with the IV contrast
      agent caused significantly higher (13% Plus 4, 35% LightSpeed 16) exposure than
      non-contrast imaging (p < 0.001). CONCLUSIONS: Great caution on the use of IV
      contrast agent and careful set-up of the AEC modulation parameters is recommended
      to avoid excessive radiation exposure on the whole-body CT imaging of young
      patients.

PMID- 28740461
TI  - Down for the count: Cryptosporidium infection depletes the gut microbiome in
      Coquerel's sifakas.
AB  - Background: The gut microbiome (GMB) is the first line of defense against enteric
      pathogens, which are a leading cause of disease and mortality worldwide. One such
      pathogen, the protozoan Cryptosporidium, causes a variety of digestive disorders
      that can be devastating and even lethal. The Coquerel's sifaka (Propithecus
      coquereli) - an endangered, folivorous primate endemic to Madagascar - is
      precariously susceptible to cryptosporidiosis under captive conditions. If left
      untreated, infection can rapidly advance to morbidity and death. Objective: To
      gain a richer understanding of the pathophysiology of this pathogen while also
      improving captive management of endangered species, we examine the impact of
      cryptosporidiosis on the GMB of a flagship species known to experience a
      debilitating disease state upon infection. Design: Using 16S sequencing of DNA
      extracted from sifaka fecal samples, we compared the microbial communities of
      healthy sifakas to those of infected individuals, across infection and recovery
      periods. Results: Over the course of infection, we found that the sifaka GMB
      responds with decreased microbial diversity and increased community
      dissimilarity. Compared to the GMB of unaffected individuals, as well as during
      pre-infection and recovery periods, the GMB during active infection was enriched
      for microbial taxa associated with dysbiosis and rapid transit time. Time to
      recovery was inversely related to age, with young animals being slowest to
      recover GMB diversity and full community membership. Antimicrobial treatment
      during infection caused a significant depletion in GMB diversity. Conclusions:
      Although individual sifakas show unique trajectories of microbial loss and
      recolonization in response to infection, recovering sifakas exhibit remarkably
      consistent patterns, similar to initial community assembly of the GMB in infants.
      This observation, in particular, provides biological insight into the rules by
      which the GMB recovers from the disease state. Fecal transfaunation may prove
      effective in restoring a healthy GMB in animals with specialized diets.

PMID- 28740462
TI  - Corrigendum: Low Latency Estimation of Motor Intentions to Assist Reaching
      Movements along Multiple Sessions in Chronic Stroke Patients: A Feasibility
      Study.
AB  - [This corrects the article on p. 126 in vol. 11, PMID: 28367109.].

PMID- 28740463
TI  - Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step
      Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and
      NeuroD2.
AB  - Cell proliferation and differentiation are interdependent processes. Here, we
      have asked to what extent the two processes of neural progenitor cell
      amplification and differentiation are functionally separated. Thus, we analyzed
      whether it is possible to rescue a defect of terminal differentiation in
      progenitor cells of the dentate gyrus, where new neurons are generated throughout
      life, by inducing their proliferation and/or their differentiation with different
      stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose
      dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect
      of terminal differentiation. We first tested the effect of two proliferative as
      well as differentiative neurogenic stimuli, one pharmacological (fluoxetine), the
      other cognitive (the Morris water maze (MWM) training). Both effectively enhanced
      the number of new dentate gyrus neurons produced, and fluoxetine also reduced the
      S-phase length of Tis21 knockout dentate gyrus progenitor cells and increased the
      rate of differentiation of control cells, but neither factor enhanced the
      defective rate of differentiation. In contrast, the defect of terminal
      differentiation was fully rescued by in vivo infection of proliferating dentate
      gyrus progenitor cells with retroviruses either silencing Id3, an inhibitor of
      neural differentiation, or expressing NeuroD2, a proneural gene expressed in
      terminally differentiated dentate gyrus neurons. This is the first demonstration
      that NeuroD2 or the silencing of Id3 can activate the differentiation of dentate
      gyrus neurons, complementing a defect of differentiation. It also highlights how
      the rate of differentiation of dentate gyrus neurons is regulated genetically at
      several levels and that a neurogenic stimulus for amplification of neural
      stem/progenitor cells may not be sufficient in itself to modify this rate.

PMID- 28740464
TI  - Neuronal Subset-Specific Migration and Axonal Wiring Mechanisms in the Developing
      Midbrain Dopamine System.
AB  - The midbrain dopamine (mDA) system is involved in the control of cognitive and
      motor behaviors, and is associated with several psychiatric and neurodegenerative
      diseases. mDA neurons receive diverse afferent inputs and establish efferent
      connections with many brain areas. Recent studies have unveiled a high level of
      molecular and cellular heterogeneity within the mDA system with specific subsets
      of mDA neurons displaying select molecular profiles and connectivity patterns.
      During mDA neuron development, molecular differences between mDA neuron subsets
      allow the establishment of subset-specific afferent and efferent connections and
      functional roles. In this review, we summarize and discuss recent work defining
      novel mDA neuron subsets based on specific molecular signatures. Then, molecular
      cues are highlighted that control mDA neuron migration during embryonic
      development and that facilitate the formation of selective patterns of efferent
      connections. The review focuses largely on studies that show differences in these
      mechanisms between different subsets of mDA neurons and for which in vivo data is
      available, and is concluded by a section that discusses open questions and
      provides directions for further research.

PMID- 28740465
TI  - Corrigendum: Microstructural Abnormalities Were Found in Brain Gray Matter from
      Patients with Chronic Myofascial Pain.
AB  - [This corrects the article on p. 122 in vol. 10, PMID: 28066193.].

PMID- 28740466
TI  - A Tyrosine-Hydroxylase Characterization of Dopaminergic Neurons in the Honey Bee
      Brain.
AB  - Dopamine (DA) plays a fundamental role in insect behavior as it acts both as a
      general modulator of behavior and as a value system in associative learning where
      it mediates the reinforcing properties of unconditioned stimuli (US). Here we
      aimed at characterizing the dopaminergic neurons in the central nervous system of
      the honey bee, an insect that serves as an established model for the study of
      learning and memory. We used tyrosine hydroxylase (TH) immunoreactivity (ir) to
      ensure that the neurons detected synthesize DA endogenously. We found three main
      dopaminergic clusters, C1-C3, which had been previously described; the C1 cluster
      is located in a small region adjacent to the esophagus (ES) and the antennal lobe
      (AL); the C2 cluster is situated above the C1 cluster, between the AL and the
      vertical lobe (VL) of the mushroom body (MB); the C3 cluster is located below the
      calyces (CA) of the MB. In addition, we found a novel dopaminergic cluster, C4,
      located above the dorsomedial border of the lobula, which innervates the visual
      neuropils of the bee brain. Additional smaller processes and clusters were found
      and are described. The profuse dopaminergic innervation of the entire bee brain
      and the specific connectivity of DA neurons, with visual, olfactory and gustatory
      circuits, provide a foundation for a deeper understanding of how these sensory
      modules are modulated by DA, and the DA-dependent value-based associations that
      occur during associative learning.

PMID- 28740467
TI  - Phosphonothioate-Based Hydrogen Sulfide Releasing Reagents: Chemistry and
      Biological Applications.
AB  - Hydrogen sulfide (H2S) is a newly recognized gasotransmitter. Studies have
      demonstrated that the production of endogenous H2S and the exogenous
      administration of H2S can regulate many physiological and/or pathological
      processes. Therefore, H2S releasing agents (also known as H2S donors) are
      important research tools in advancing our understanding of the biology and
      clinical potential of H2S. Among currently available donors, GYY4137 is probably
      the most well-known and has been used in many studies in the past 10 years.
      Recently, a number of GYY4137 derivatives (e.g., phosphonothioate-based
      compounds) have been developed as H2S donors. In this review, we summarize the
      development and application of these donors, which include Lawesson's reagent,
      substituted phosphorodithioates, cyclic phosphorane analogs, and pH-controlled
      phosphonamidothioates (JK donors). These donors have advantages such as good
      water-solubility, slow and controllable H2S release capability, and a variety of
      reported biological activities. However, it should be noted that the detailed H2S
      release profiles and byproducts under real biological systems are still unclear
      for many of these donors. Only after we figure out these unknowns we will see
      better applications of these donors in H2S research and therapy.

PMID- 28740468
TI  - Evolution of Precision Medicine and Surgical Strategies for Bicuspid Aortic Valve
      Associated Aortopathy.
AB  - Bicuspid aortic valve (BAV) is a common congenital cardiac malformation affecting
      1-2% of people. BAV results from fusion of two adjacent aortic valve cusps, and
      is associated with dilatation of the aorta, known as bicuspid valve associated
      aortopathy. Bicuspid valve aortopathy is progressive and associated with
      catastrophic clinical events, such as aortic dissection and rupture. Therefore,
      frequent monitoring and early intervention with prophylactic surgical resection
      of the proximal aorta is often recommended. However, the specific pattern of
      aortopathy is highly variable among patients, with different segments of the
      ascending aorta being affected. Individual patient risks are sometimes difficult
      to predict. Resection strategies are informed by current surgical guidelines
      which are primarily based on aortic size and growth criteria. These criteria may
      not optimally reflect the risk of important aortic events. To address these
      issues in the care of patients with bicuspid valve aortopathy, our translational
      research group has focused on validating use of novel imaging techniques to
      establish non-invasive hemodynamic biomarkers for risk-stratifying BAV patients.
      In this article, we review recent efforts, successes, and ongoing challenges in
      the development of more precise and individualized surgical approaches for
      patients with bicuspid aortic valves and associated aortic disease.

PMID- 28740469
TI  - Neuroligins Nlg2 and Nlg4 Affect Social Behavior in Drosophila melanogaster.
AB  - The genome of Drosophila melanogaster includes homologs to approximately one
      third of the currently known human disease genes. Flies and humans share many
      biological processes, including the principles of information processing by
      excitable neurons, synaptic transmission, and the chemical signals involved in
      intercellular communication. Studies on the molecular and behavioral impact of
      genetic risk factors of human neuro-developmental disorders [autism spectrum
      disorders (ASDs), schizophrenia, attention deficit hyperactivity disorders, and
      Tourette syndrome] increasingly use the well-studied social behavior of D.
      melanogaster, an organism that is amenable to a large variety of genetic
      manipulations. Neuroligins (Nlgs) are a family of phylogenetically conserved
      postsynaptic adhesion molecules present (among others) in nematodes, insects, and
      mammals. Impaired function of Nlgs (particularly of Nlg 3 and 4) has been
      associated with ASDs in humans and impaired social and communication behavior in
      mice. Making use of a set of behavioral and social assays, we, here, analyzed the
      impact of two Drosophila Nlgs, Dnlg2 and Dnlg4, which are differentially
      expressed at excitatory and inhibitory central nervous synapses, respectively.
      Both Nlgs seem to be associated with diurnal activity and social behavior. Even
      though deficiencies in Dnlg2 and Dnlg4 appeared to have no effects on sensory or
      motor systems, they differentially impacted on social interactions, suggesting
      that social behavior is distinctly regulated by these Nlgs.

PMID- 28740470
TI  - Manual Dexterity in Schizophrenia-A Neglected Clinical Marker?
AB  - Impaired manual dexterity is commonly observed in schizophrenia. However, a
      quantitative description of key sensorimotor components contributing to impaired
      dexterity is lacking. Whether the key components of dexterity are differentially
      affected and how they relate to clinical characteristics also remains unclear. We
      quantified the degree of dexterity in 35 stabilized patients with schizophrenia
      and in 20 age-matched control subjects using four visuomotor tasks: (i) force
      tracking to quantify visuomotor precision, (ii) sequential finger tapping to
      measure motor sequence recall, (iii) single-finger tapping to assess temporal
      regularity, and (iv) multi-finger tapping to measure independence of finger
      movements. Diverse clinical and neuropsychological tests were also applied. A
      patient subgroup (N = 15) participated in a 14-week cognitive remediation
      protocol and was assessed before and after remediation. Compared to control
      subjects, patients with schizophrenia showed greater error in force tracking,
      poorer recall of tapping sequences, decreased tapping regularity, and reduced
      degree of finger individuation. A composite performance measure discriminated
      patients from controls with sensitivity = 0.79 and specificity = 0.9. Aside from
      force-tracking error, no other dexterity components correlated with antipsychotic
      medication. In patients, some dexterity components correlated with neurological
      soft signs, Positive and Negative Syndrome Scale (PANSS), or neuropsychological
      scores. This suggests differential cognitive contributions to these components.
      Cognitive remediation lead to significant improvement in PANSS, tracking error,
      and sequence recall (without change in medication). These findings show that
      multiple aspects of sensorimotor control contribute to impaired manual dexterity
      in schizophrenia. Only visuomotor precision was related to antipsychotic
      medication. Good diagnostic accuracy and responsiveness to treatment suggest that
      manual dexterity may represent a useful clinical marker in schizophrenia.

PMID- 28740471
TI  - No Evidence of Narrowly Defined Cognitive Penetrability in Unambiguous Vision.
AB  - The classical notion of cognitive impenetrability suggests that perceptual
      processing is an automatic modular system and not under conscious control. Near
      consensus is now emerging that this classical notion is untenable. However, as
      recently pointed out by Firestone and Scholl, this consensus is built on
      quicksand. In most studies claiming perception is cognitively penetrable, it
      remains unclear which actual process has been affected (perception, memory,
      imagery, input selection or judgment). In fact, the only available "proofs" for
      cognitive penetrability are proxies for perception, such as behavioral responses
      and neural correlates. We suggest that one can interpret cognitive penetrability
      in two different ways, a broad sense and a narrow sense. In the broad sense,
      attention and memory are not considered as "just" pre- and post-perceptual
      systems but as part of the mechanisms by which top-down processes influence the
      actual percept. Although many studies have proven top-down influences in this
      broader sense, it is still debatable whether cognitive penetrability remains
      tenable in a narrow sense. The narrow sense states that cognitive penetrability
      only occurs when top-down factors are flexible and cause a clear illusion from a
      first person perspective. So far, there is no strong evidence from a first person
      perspective that visual illusions can indeed be driven by high-level flexible
      factors. One cannot be cognitively trained to see and unsee visual illusions. We
      argue that this lack of convincing proof for cognitive penetrability in the
      narrow sense can be explained by the fact that most research focuses on foveal
      vision only. This type of perception may be too unambiguous for transient high
      level factors to control perception. Therefore, illusions in more ambiguous
      perception, such as peripheral vision, can offer a unique insight into the
      matter. They produce a clear subjective percept based on unclear, degraded visual
      input: the optimal basis to study narrowly defined cognitive penetrability.

PMID- 28740472
TI  - The Benefits of Working Memory Capacity on Attentional Control under Pressure.
AB  - The present study aimed to examine the effects of working memory capacity (WMC)
      and state anxiety (SA) on attentional control. WMC was manipulated by (a)
      dividing participants into low- and high-WMC groups (Experiment 1), and (b) using
      working memory training to improve WMC (Experiment 2). SA was manipulated by
      creating low- and high-SA conditions. Attentional control was evaluated by using
      antisaccade task. Results demonstrated that (a) higher WMC indicated better
      attentional control (Experiments 1 and 2); (b) the effects of SA on attentional
      control were inconsistent because SA impaired attentional control in Experiment
      1, but favored attentional control in Experiment 2; and (c) the interaction of SA
      and WMC was not significant (Experiments 1 and 2). This study directly
      manipulated WMC by working memory training, which provided more reliable evidence
      for controlled attention view of WMC and new supportive evidence for working
      memory training (i.e., far transfer effect on attentional control). And the
      refinement of the relationship between anxiety and attentional control proposed
      by Attentional Control Theory was also discussed.

PMID- 28740473
TI  - Bonding Pictures: Affective Ratings Are Specifically Associated to Loneliness But
      Not to Empathy.
AB  - Responding to pro-social cues plays an important adaptive role in humans. Our
      aims were (i) to create a catalog of bonding and matched-control pictures to
      compare the emotional reports of valence and arousal with the International
      Affective Picture System (IAPS) pictures; (ii) to verify sex influence on the
      valence and arousal of bonding and matched-control pictures; (iii) to investigate
      if empathy and loneliness traits exert a specific influence on emotional reports
      for the bonding pictures. To provide a finer tool for social interaction studies,
      the present work defined two new sets of pictures consisting of "interacting
      dyads" (Bonding: N = 70) and matched controls "non-interacting dyads" (Controls:
      N = 70). The dyads could be either a child and an adult, or two children.
      Participants (N = 283, 182 women) were divided in 10 groups for the experimental
      sessions. The task was to rate the hedonic valence and emotional arousal of
      bonding and controls; and of pleasant, neutral, and unpleasant pictures from the
      IAPS. Effects of social-related traits, empathy and loneliness, on affective
      ratings were tested. Participants rated bonding pictures as more pleasant and
      arousing than control ones. Ratings did not differentiate bonding from IAPS
      pleasant pictures. Control pictures showed lower ratings than pleasant but higher
      ratings than neutral IAPS pictures. Women rated bonding and control pictures as
      more positive than men. There was no sex difference for arousal ratings. High
      empathic participants rated bonding and control pictures higher than low empathic
      participants. Also, they rated pleasant IAPS pictures more positive and arousing;
      and unpleasant pictures more negative and arousing than the less empathic ones.
      Loneliness trait, on the other hand, affected very specifically the ratings of
      bonding pictures; lonelier participants rated them less pleasant and less
      arousing than less lonely. Loneliness trait did not modulate ratings of other
      categories. In conclusion, high empathy seems related to emotional strength in
      general, while high loneliness seems to weaken the engagement in social
      interaction cues.

PMID- 28740474
TI  - Pre-cueing, the Epistemic Role of Early Vision, and the Cognitive Impenetrability
      of Early Vision.
AB  - I have argued (Raftopoulos, 2009, 2014) that early vision is not directly
      affected by cognition since its processes do not draw on cognition as an
      informational resource; early vision processes do not operate over cognitive
      contents, which is the essence of the claim that perception is cognitively
      penetrated; early vision is cognitively impenetrable. Recently it has been argued
      that there are cognitive effects that affect early vision, such as the various
      pre-cueing effects guided by cognitively driven attention, which suggests that
      early vision is cognitively penetrated. In addition, since the signatures of
      these effects are found in early vision it seems that early vision is directly
      affected by cognition since its processes seem to use cognitive information. I
      defend the cognitive impenetrability of early vision in three steps. First, I
      discuss the problems the cognitively penetrability of perception causes for the
      epistemic role of perception in grounding perceptual beliefs. Second, I argue
      that whether a set of perceptual processes is cognitively penetrated hinges on
      whether there are cognitive effects that undermine the justificatory role of
      these processes in grounding empirical beliefs, and I examine the epistemic role
      of early vision. I argue, third, that the cognitive effects that act through pre
      cueing do not undermine this role and, thus, do not render early vision
      cognitively penetrable. In addition, they do not entail that early vision uses
      cognitive information.

PMID- 28740475
TI  - The Cognitive Information Effect of Televised News.
AB  - The purpose of this review is to summarize the key findings which prove that the
      biased perceptions of viewers may provide an inaccurate image of the
      informational validity of televised news. The news may generate distorted
      recollections of what occurred in particular reported events if displayed
      routines influence viewers not to pay attention to the essential features of a
      narrative. Elaborating on Fiske and Hartley (2010), Zelizer (2010), and Gunter
      (2015), we indicate that the character of the news setting has altered and
      individuals' news consumption routines have changed in adapting to media
      advancements. The news may be undergone at various psychological stages by news
      publics. Televised news may transmit information undeviatingly to publics that
      may (not) be committed successfully to memory. Our paper shows that individuals'
      skills to handle information that is displayed in a linguistic configuration are
      influenced by their abilities in the utilization of certain symbol systems that
      are employed to represent notions and meanings. Televised news may shape what
      individuals grasp, influence their perceptions, convictions, and views regarding
      prevailing events and matters, and transmit knowledge and interpretation. If news
      stories can be jotted down in a linguistic style that sidesteps making needless
      processing demands and captivate news users by facilitating them to make
      connections with former knowledge, they may be more worthy of note and more
      edifying. We conclude that news narratives present a cognitive demanding task to
      individuals, displaying novel information regarding evolving events in a
      multifarious format. Broadcast news exhibits intricate contents, displaying
      configurations that employ excessively the cognitive abilities for information
      processing of viewers.

PMID- 28740476
TI  - Parental Education and Aggressive Behavior in Children: A Moderated-Mediation
      Model for Inhibitory Control and Gender.
AB  - Aggressive behaviors are highly prevalent in children. Given their negative
      consequences, it is necessary to look for protective factors that prevent or
      reduce their progress in early development before they become highly unshakable.
      With a sample of 147 children, the present study aimed to assess the relation
      between parental education and inhibitory control in the aggressive behavior of
      children aged from 7 to 10 years. The participants completed a go/no-go task to
      assess inhibitory control, whilst their parents reported their education level,
      and their teachers rated the aggressive behavior of the children through the
      Teacher Rating Scale (TRS) of the Behavior Assessment System for Children 2 (BASC
      2). The results showed that both parental education and inhibitory control
      determined aggressive behavior in children. In addition, inhibitory control
      partially mediated the associations between parental education and aggressive
      behavior after accounting for age. However, a moderated mediation model revealed
      that lower parental education was associated with higher levels of aggressive
      behavior, which, in girls occurred independently of inhibitory control. In
      contrast, inhibitory control mediated this relation in boys. These results
      suggest the importance of parental education and inhibitory control in the
      aggressive behavior of children, supporting the idea that both constructs are
      relevant for understanding these conduct problems in schools, particularly in
      boys. The clinical implications of these findings are discussed, along with
      possible future lines of investigation.

PMID- 28740477
TI  - Corrigendum: "To be or not to be Retained... That's the Question!" Retention,
      Self-esteem, Self-concept, Achievement Goals and Grades.
AB  - [This corrects the article on p. 1550 in vol. 7, PMID: 27790167.].

PMID- 28740478
TI  - Corrigendum: Cognitive Investments in Academic Success: The Role of Need for
      Cognition at University.
AB  - [This corrects the article on p. 790 in vol. 8, PMID: 28559876.].

PMID- 28740479
TI  - Non-Ischemic Cerebral Energy Dysfunction at the Early Brain Injury Phase
      following Aneurysmal Subarachnoid Hemorrhage.
AB  - BACKGROUND: The pathophysiology of early brain injury following aneurysmal
      subarachnoid hemorrhage (SAH) is still not completely understood. OBJECTIVE:
      Using brain perfusion CT (PCT) and cerebral microdialysis (CMD), we examined
      whether non-ischemic cerebral energy dysfunction may be a pathogenic determinant
      of EBI. METHODS: A total of 21 PCTs were performed (a median of 41 h from ictus
      onset) among a cohort of 18 comatose mechanically ventilated SAH patients (mean
      age 58 years, median admission WFNS score 4) who underwent CMD and brain tissue
      PO2 (PbtO2) monitoring. Cerebral energy dysfunction was defined as CMD episodes
      with lactate/pyruvate ratio (LPR) >40 and/or lactate >4 mmol/L. PCT-derived
      global CBF was categorized as oligemic (CBF < 28 mL/100 g/min), normal (CBF 28-65
      mL/100 g/min), or hyperemic (CBF 69-85 mL/100 g/min), and was matched to
      CMD/PbtO2 data. RESULTS: Global CBF (57 +/- 14 mL/100 g/min) and PbtO2 (25 +/- 9
      mm Hg) were within normal ranges. Episodes with cerebral energy dysfunction (n =
      103 h of CMD samples, average duration 7.4 h) were frequent (66% of CMD samples)
      and were associated with normal or hyperemic CBF. CMD abnormalities were more
      pronounced in conditions of hyperemic vs. normal CBF (LPR 54 +/- 12 vs. 42 +/- 7,
      glycerol 157 +/- 76 vs. 95 +/- 41 umol/L; both p < 0.01). Elevated brain LPR
      correlated with higher CBF (r = 0.47, p < 0.0001). CONCLUSION: Cerebral energy
      dysfunction is frequent at the early phase following poor-grade SAH and is
      associated with normal or hyperemic brain perfusion. Our data support the notion
      that mechanisms alternative to ischemia/hypoxia are implicated in the
      pathogenesis of early brain injury after SAH.

PMID- 28740481
TI  - Refractory Hypothyroidism Due to Improper Storage of Levothyroxine Tablets.
AB  - CONTEXT: A not negligible part of hypothyroid patients on levothyroxine therapy
      do not normalize serum thyrotropin (TSH) concentrations. "Refractory
      hypothyroidism," i.e., a condition characterized by persistently abnormal serum
      TSH levels despite adequate titration of l-T4 substitution therapy, requires
      biochemical and instrumental investigation, but no definite etiology is found in
      up to 15% of cases. OBJECTIVE: To report patients presenting with refractory
      hypothyroidism with proven improper storage of levothyroxine tablets. DESIGN:
      Patients on l-T4 substitution therapy referred to three Italian outpatient
      Clinics of Endocrinology between January 2013 and December 2015 for refractory
      hypothyroidism were investigated for levothyroxine tablet exposure to humidity,
      light, and high temperature. RESULTS: We report eight patients, accounting for
      approximately 1% of all hypothyroid patients and 5% of those with refractory
      hypothyroidism in our series. Careful anamnesis disclosed that these patients
      stored levothyroxine tablets inappropriately. Normalization of serum TSH
      concentrations was obtained in all cases by simply recommending to store the new
      levothyroxine tablets away from heat, light, and humidity. CONCLUSION: Refractory
      hypothyroidism linked to improper storage of l-T4 tablets does exist and might be
      an underrecognized entity. In addition to proper modalities of ingestion of l-T4
      tablets, patients need to be instructed on proper modalities of storage, as well.

PMID- 28740480
TI  - Cerebrospinal Fluid and Microdialysis Cytokines in Severe Traumatic Brain Injury:
      A Scoping Systematic Review.
AB  - OBJECTIVE: To perform two scoping systematic reviews of the literature on
      cytokine measurement in: 1. cerebral microdialysis (CMD) and 2. cerebrospinal
      fluid (CSF) in severe traumatic brain injury (TBI) patients. METHODS: Two
      separate systematic reviews were conducted: one for CMD cytokines and the second
      for CSF cytokines. Both were conducted in severe TBI (sTBI) patients only. DATA
      SOURCES: Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane
      Library (inception to October 2016), reference lists of relevant articles, and
      gray literature were searched. STUDY SELECTION: Two reviewers independently
      identified all manuscripts utilizing predefined inclusion/exclusion criteria. A
      two-tier filter of references was conducted. DATA EXTRACTION: Patient demographic
      and study data were extracted to tables. RESULTS: There were 19 studies
      identified describing the analysis of cytokines via CMD in 267 sTBI patients.
      Similarly, there were 32 studies identified describing the analysis of CSF
      cytokines in 1,363 sTBI patients. The two systematic reviews demonstrated: 1.
      limited literature available on CMD cytokine measurement in sTBI, with some
      preliminary data supporting feasibility of measurement and associations between
      cytokines and patient outcome. 2. Various CSF measured cytokines may be
      associated with patient outcome at 6-12 months, including interleukin (IL)-1b, IL
      1ra, IL-6, IL-8, IL-10, and tumor necrosis factor 3. There is little to no
      literature in support of an association between CSF cytokines and
      neurophysiologic or tissue outcomes. CONCLUSION: The evaluation of CMD and CSF
      cytokines is an emerging area of the literature in sTBI. Further, large
      prospective multicenter studies on cytokines in CMD and CSF need to be conducted.

PMID- 28740482
TI  - Both Low Blood Glucose and Insufficient Treatment Confer Risk of
      Neurodevelopmental Impairment in Congenital Hyperinsulinism: A Multinational
      Cohort Study.
AB  - BACKGROUND/AIMS: Congenital hyperinsulinism (CHI) is a heterogeneous disease most
      frequently caused by KATP-channel (ABCC8 and KCNJ11) mutations, with neonatal or
      later onset, variable severity, and with focal or diffuse pancreatic involvement
      as the two major histological types. CHI confers a high risk of neurological
      impairment; however, sparsely studied in larger patient series. We assessed the
      neurodevelopmental outcome in children with CHI at follow-up in a mixed
      international cohort. METHODS: In two hyperinsulinism expert centers, 75 CHI
      patients were included (Russian, n = 33, referred non-Scandinavian, treated in
      Denmark n = 27, Scandinavian, n = 15). Hospital files were reviewed. At follow
      up, neurodevelopmental impairment and neurodevelopmental, cognitive and motor
      function scores were assessed. RESULTS: Median (range) age at follow-up was 3.7
      years (3.3 months-18.2 years). Neurodevelopmental impairment was seen in 35
      (47%). Impairment was associated with abnormal brain magnetic resonance imaging
      (MRI); odds ratio (OR) (95% CI) 15.0 (3.0-74.3), p = 0.001; lowest recorded blood
      glucose <=1 mmol/L; OR 3.8 (1.3-11.3), p = 0.015, being non-Scandinavian patient,
      OR 3.8 (1.2-11.9), p = 0.023; and treatment delay from first symptom to expert
      center >5 days; OR 4.0 (1.0-16.6), trend p = 0.05. In multivariate analysis (n =
      31) for early predictors with exclusion of brain MRI, treatment delay from first
      symptom to expert center >5 days conferred a significantly increased risk of
      neurodevelopment impairment, adjusted OR (aOR) 15.6 (1.6-146.7), p = 0.016, while
      lowest blood glucose <=1 mmol/L had a trend toward increased risk, aOR 3.5 (1.1
      14.3), p = 0.058. No associations for early vs. late disease onset, KATP-channel
      mutations, disease severity, focal vs. diffuse disease, or age at follow-up were
      seen in uni- or multivariate analysis. CONCLUSION: Not only very low blood
      glucose, but also insufficient treatment as expressed by delay until expert
      center hospitalization, increased the risk of neurodevelopmental impairment. This
      novel finding calls for improvements in spread of knowledge about CHI among
      health-care personnel and rapid contact with an expert CHI center on suspicion of
      CHI.

PMID- 28740483
TI  - A Case with Spondyloenchondrodysplasia Treated with Growth Hormone.
AB  - Spondyloenchondrodysplasia (SPENCD) is an autosomal recessive skeletal dysplasia
      caused by loss of function mutations in acid phosphatase 5, tartrate resistant
      (ACP5). Hypomorphic ACP5 mutations impair endochondral bone growth and create an
      interferon (INF) signature, which lead to distinctive spondylar and metaphyseal
      dysplasias, and extraskeletal morbidity, such as neurological involvement and
      immune dysregulation, respectively. We report an affected boy with novel ACP5
      mutations, a splice-site mutation (736-2 A>C) and a nonsense mutation (R176X). He
      presented with postnatal short stature, which led to a diagnosis of partial
      growth hormone (GH) deficiency at 3 years of age. GH therapy was beneficial in
      accelerating his growth velocity. At 6 years of age, however, metaphyseal
      abnormalities of the knee attracted medical attention, and subsequent assessment
      ascertained the typical skeletal phenotype of SPENCD, brain calcifications, and
      an INF signature. This anecdotal experience indicates the potential efficacy of
      GH for growth failure in SPENCD.

PMID- 28740484
TI  - Corrigendum: Contemporary Medical Management of Primary Hyperparathyroidism: A
      Systematic Review.
AB  - [This corrects the article on p. 79 in vol. 8, PMID: 28473803.].

PMID- 28740485
TI  - Tuftsin-Phosphorylcholine Maintains Normal Gut Microbiota in Collagen Induced
      Arthritic Mice.
AB  - Rheumatoid arthritis (RA) is characterized by chronic autoinflammation of the
      joints, with a prevalence of about 1% in Western populations. Evidence in recent
      years has linked RA to changes in the gut microbiota (dysbiosis). Interestingly,
      helminths have been shown to have therapeutic activity in RA. Specifically, a
      glycoprotein containing phosphorylcholine (PC) extracted from helminths was found
      to have immunomodulatory activity. We have previously developed a novel chimeric
      compound composed of tuftsin-PC (TPC) that attenuates the joint destruction in
      mice with collagen-induced arthritis (CIA). Here, we address the
      interrelationship between TPC immunomodulatory activity and the gut microbiota in
      CIA mice. Preventive therapy with TPC in mice with arthritis maintained a
      physiological arthritis score as well as a steady gut microbial environment,
      similar to that of healthy controls, in contrast to CIA mice with severe disease.
      The microbial composition differed significantly between healthy and phosphate
      buffered saline-treated CIA mice, enabling classifying test samples by machine
      learning based on levels of a small number of bacterial species. Using these
      bacterial biomarkers, all TPC-treated CIA mice were classified as healthy. Thus,
      we describe a clear correlation between TPC treatment, healthy gut microbial
      communities, and prevention of arthritis. This is the first study to demonstrate
      the immunomodulatory effect of helminth derivatives in autoimmune diseases and
      the link to gut microbiota.

PMID- 28740486
TI  - Evolution of Acinetobacter baumannii In Vivo: International Clone II, More
      Resistance to Ceftazidime, Mutation in ptk.
AB  - Acinetobacter baumannii is an important nosocomial pathogen worldwide. A more
      comprehensive understanding of the within-host genomic evolution of A. baumannii
      would provide a molecule basis for improving treatment of A. baumannii infection.
      To understand the evolutionary mechanism facilitating A. baumannii survived in
      human body, we here reported the genomic analysis of A. baumannii isolated
      sampled from Chinese patients. We used whole-genome sequence of A. baumannii
      isolates from the same patient to determine single-nucleotide variants, insertion
      sequence mapping, and gene change. The MICs for 10 antimicrobial agents were
      determined. Motility assay and microscopy were performed on the isolated pairs
      harboring ptk mutations. The gene ptk encoded a putative protein tyrosine kinase
      involved in the production of capsular polysaccharide. Approximately half (39/86)
      of the strains isolated from the same patient harbored the same MLST patterns,
      and during the replacement of international clonal lineage II (ICL-II) and non
      ICL-II strains, most of the alteration was that non-ICL-II strain was replaced by
      ICL-II strain (10/12). A. baumannii was resistant to major antimicrobial agents,
      whereas the strains were more resistant to ceftazidime, azithromycin, and
      sulfonamides after within-host evolution. Isolates from the ICL-II lineage
      displayed greater resistance to antimicrobial agents than non-ICL-II isolates.
      Isolates from ICL-II harbored more resistance genes and mobile elements than non
      ICL-II strains. Several lineages evolved a more mucoid phenotype. Genome
      sequencing revealed that the phenotype was achieved by genetic changes in the ptk
      gene. ICL-II (especially ST195 and ST208) was the terminal destination for
      bacteria after within-host evolution. These results indicate that the molecular
      basis and the treatment for ICL-II strains needed further investigation.

PMID- 28740488
TI  - Regulatory 3' Untranslated Regions of Bacterial mRNAs.
AB  - The untranslated regions (UTRs) of mRNA contain important features that are
      relevant to the post-transcriptional and translational regulation of gene
      expression. Most studies of bacterial UTRs have focused on the 5'regions;
      however, 3'UTRs have recently emerged as a new class of post-transcriptional
      regulatory elements. 3'UTRs were found to regulate the decay and translation
      initiation in their own mRNAs. In addition, 3'UTRs constitute a rich reservoir of
      small regulatory RNAs, regulating target gene expression. In the current review,
      we describe several recently discovered examples of bacterial regulatory 3'UTRs,
      discuss their modes of action, and illustrate how they facilitate gene regulation
      in various environments.

PMID- 28740489
TI  - Prophage Integrase Typing Is a Useful Indicator of Genomic Diversity in
      Salmonella enterica.
AB  - Salmonella enterica is a bacterial species that is a major cause of illness in
      humans and food-producing animals. S. enterica exhibits considerable inter
      serovar diversity, as evidenced by the large number of host adapted serovars that
      have been identified. The development of methods to assess genome diversity in S.
      enterica will help to further define the limits of diversity in this foodborne
      pathogen. Thus, we evaluated a PCR assay, which targets prophage integrase genes,
      as a rapid method to investigate S. enterica genome diversity. To evaluate the
      PCR prophage integrase assay, 49 isolates of S. enterica were selected, including
      19 clinical isolates from clonal serovars (Enteritidis and Heidelberg) that
      commonly cause human illness, and 30 isolates from food-associated Salmonella
      serovars that rarely cause human illness. The number of integrase genes
      identified by the PCR assay was compared to the number of integrase genes within
      intact prophages identified by whole genome sequencing and phage finding program
      PHASTER. The PCR assay identified a total of 147 prophage integrase genes within
      the 49 S. enterica genomes (79 integrase genes in the food-associated Salmonella
      isolates, 50 integrase genes in S. Enteritidis, and 18 integrase genes in S.
      Heidelberg). In comparison, whole genome sequencing and PHASTER identified a
      total of 75 prophage integrase genes within 102 intact prophages in the 49 S.
      enterica genomes (44 integrase genes in the food-associated Salmonella isolates,
      21 integrase genes in S. Enteritidis, and 9 integrase genes in S. Heidelberg).
      Collectively, both the PCR assay and PHASTER identified the presence of a large
      diversity of prophage integrase genes in the food-associated isolates compared to
      the clinical isolates, thus indicating a high degree of diversity in the food
      associated isolates, and confirming the clonal nature of S. Enteritidis and S.
      Heidelberg. Moreover, PHASTER revealed a diversity of 29 different types of
      prophages and 23 different integrase genes within the food-associated isolates,
      but only identified four different phages and integrase genes within clonal
      isolates of S. Enteritidis and S. Heidelberg. These results demonstrate the
      potential usefulness of PCR based detection of prophage integrase genes as a
      rapid indicator of genome diversity in S. enterica.

PMID- 28740487
TI  - Determinants of Bacterial Morphology: From Fundamentals to Possibilities for
      Antimicrobial Targeting.
AB  - Bacterial morphology is extremely diverse. Specific shapes are the consequence of
      adaptive pressures optimizing bacterial fitness. Shape affects critical
      biological functions, including nutrient acquisition, motility, dispersion,
      stress resistance and interactions with other organisms. Although the
      characteristic shape of a bacterial species remains unchanged for vast numbers of
      generations, periodical variations occur throughout the cell (division) and life
      cycles, and these variations can be influenced by environmental conditions.
      Bacterial morphology is ultimately dictated by the net-like peptidoglycan (PG)
      sacculus. The species-specific shape of the PG sacculus at any time in the cell
      cycle is the product of multiple determinants. Some morphological determinants
      act as a cytoskeleton to guide biosynthetic complexes spatiotemporally, whereas
      others modify the PG sacculus after biosynthesis. Accumulating evidence supports
      critical roles of morphogenetic processes in bacteria-host interactions,
      including pathogenesis. Here, we review the molecular determinants underlying
      morphology, discuss the evidence linking bacterial morphology to niche adaptation
      and pathogenesis, and examine the potential of morphological determinants as
      antimicrobial targets.

PMID- 28740490
TI  - Inhibition of the NOD-Like Receptor Protein 3 Inflammasome Is Protective in
      Juvenile Influenza A Virus Infection.
AB  - Influenza A virus (IAV) is a significant cause of life-threatening lower
      respiratory tract infections in children. Antiviral therapy is the mainstay of
      treatment, but its effectiveness in this age group has been questioned. In
      addition, damage inflicted on the lungs by the immune response to the virus may
      be as important to the development of severe lung injury during IAV infection as
      the cytotoxic effects of the virus itself. A crucial step in the immune response
      to IAV is activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and
      the subsequent secretion of the inflammatory cytokines, interleukin-1beta (IL
      1beta), and interleukin-18 (IL-18). The IAV matrix 2 proton channel (M2) has been
      shown to be an important activator of the NLRP3 inflammasome during IAV
      infection. We sought to interrupt this ion channel-mediated activation of the
      NLRP3 inflammasome through inhibition of NLRP3 or the cytokine downstream from
      its activation, IL-1beta. Using our juvenile mouse model of IAV infection, we
      show that inhibition of the NLRP3 inflammasome with the small molecule inhibitor,
      MCC950, beginning 3 days after infection with IAV, improves survival in juvenile
      mice. Treatment with MCC950 reduces NLRP3 levels in lung homogenates, decreases
      IL-18 secretion into the alveolar space, and inhibits NLRP3 inflammasome
      activation in alveolar macrophages. Importantly, inhibition of the NLRP3
      inflammasome with MCC950 does not impair viral clearance. In contrast, inhibition
      of IL-1beta signaling with the IL-1 receptor antagonist, anakinra, is
      insufficient to protect juvenile mice from IAV. Our findings suggest that
      targeting the NLRP3 inflammasome in juvenile IAV infection may improve disease
      outcomes in this age group.

PMID- 28740491
TI  - NOD-Like Receptor P3 Inflammasome Controls Protective Th1/Th17 Immunity against
      Pulmonary Paracoccidioidomycosis.
AB  - The NOD-like receptor P3 (NLRP3) inflammasome is an intracellular multimeric
      complex that triggers the activation of inflammatory caspases and the maturation
      of IL-1beta and IL-18, important cytokines for the innate immune response against
      pathogens. The functional NLRP3 inflammasome complex consists of NLRP3, the
      adaptor protein apoptosis-associated speck-like protein, and caspase-1. Various
      molecular mechanisms were associated with NLRP3 activation including the presence
      of extracellular ATP, recognized by the cell surface P2X7 receptor (P2X7R).
      Several pattern recognition receptors on innate immune cells recognize
      Paracoccidioides brasiliensis components resulting in diverse responses that
      influence adaptive immunity and disease outcome. However, the role of NLRP3
      inflammasome was scantily investigated in pulmonary paracoccidioidomycosis (PCM),
      leading us to use an intratracheal (i.t.) model of infection to study the
      influence of this receptor in anti-fungal immunity and severity of infection. For
      in vivo studies, C57BL/6 mice deficient for several NLRP3 inflammasome components
      (Nlrp3-/-, Casp1/11-/-, Asc-/-) as well as deficient for ATP receptor (P2x7r-/-)
      were infected via i.t. with P. brasiliensis and several parameters of immunity
      and disease severity analyzed at the acute and chronic periods of infection.
      Pulmonary PCM was more severe in Nlrp3-/-, Casp1/11-/-, Asc-/-, and P2x7r-/- mice
      as demonstrated by the increased fungal burdens, mortality rates and tissue
      pathology developed. The more severe disease developed by NLRP3, ASC, and Caspase
      1/11 deficient mice was associated with decreased production of IL-1beta and IL
      18 and reduced inflammatory reactions mediated by PMN leukocytes and activated
      CD4+ and CD8+ T cells. The decreased T cell immunity was concomitant with
      increased expansion of CD4+CD25+Foxp3 regulatory T (Treg) cells. Characterization
      of intracellular cytokines showed a persistent reduction of CD4+ and CD8+ T cells
      expressing IFN-gamma and IL-17 whereas those producing IL-4 and TGF-beta appeared
      in increased frequencies. Histopathological studies showed that all deficient
      mouse strains developed more severe lesions containing elevated numbers of
      budding yeast cells resulting in increased mortality rates. Altogether, these
      findings led us to conclude that the activation of the NLRP3 inflammasome has a
      crucial role in the immunoprotection against pulmonary PCM by promoting the
      expansion of Th1/Th17 immunity and reducing the suppressive control mediated by
      Treg cells.

PMID- 28740492
TI  - Patterns of Early-Life Gut Microbial Colonization during Human Immune
      Development: An Ecological Perspective.
AB  - Alterations in gut microbial colonization during early life have been reported in
      infants that later developed asthma, allergies, type 1 diabetes, as well as in
      inflammatory bowel disease patients, previous to disease flares. Mechanistic
      studies in animal models have established that microbial alterations influence
      disease pathogenesis via changes in immune system maturation. Strong evidence
      points to the presence of a window of opportunity in early life, during which
      changes in gut microbial colonization can result in immune dysregulation that
      predisposes susceptible hosts to disease. Although the ecological patterns of
      microbial succession in the first year of life have been partly defined in
      specific human cohorts, the taxonomic and functional features, and diversity
      thresholds that characterize these microbial alterations are, for the most part,
      unknown. In this review, we summarize the most important links between the
      temporal mosaics of gut microbial colonization and the age-dependent immune
      functions that rely on them. We also highlight the importance of applying ecology
      theory to design studies that explore the interactions between this complex
      ecosystem and the host immune system. Focusing research efforts on understanding
      the importance of temporally structured patterns of diversity, keystone groups,
      and inter-kingdom microbial interactions for ecosystem functions has great
      potential to enable the development of biologically sound interventions aimed at
      maintaining and/or improving immune system development and preventing disease.

PMID- 28740493
TI  - Impact of Enhancer of Zeste Homolog 2 on T Helper Cell-Mediated Allergic
      Rhinitis.
AB  - Enhancer of zeste homolog 2 (Ezh2) has been shown to play a role in the
      differentiation of T helper (Th) 1 and 2 cells in mice studies using Ezh2
      deficient T cells. However, the results have been inconsistent, and the function
      of Ezh2 in human Th1 and Th2 cell differentiation and its association with
      disease remains controversial. We measured the expression of Ezh2 in Th1 and Th2
      cells in peripheral blood mononuclear cells after acute challenge with house dust
      mite using flow cytometry in patients with allergic rhinitis (AR) and controls.
      The role of Ezh2 was further explored by adding the p38 inhibitor to see if this
      affected allergen-induced Th1 and Th2 differentiation. The expression of Ezh2 in
      the Th1 and Th2 cells was significantly lower in the patients than in the
      controls and was negatively correlated with serum IL-17A levels in the patients.
      Ex vivo allergen challenge resulted in rapid Th2 cell differentiation, which was
      negatively associated with the Ezh2 expression in Th2 cells. Inhibiting p38
      activity increased the expression of Ezh2 in Th2 cells and reduced the number of
      differentiated Th2 cells. Our findings suggest that Ezh2 expression is
      potentially associated with AR development.

PMID- 28740494
TI  - Insights in Anaphylaxis and Clonal Mast Cell Disorders.
AB  - The prevalence of anaphylaxis among patients with clonal mast cell disorders
      (MCD) is clearly higher comparing to the general population. Due to a lower
      frequency of symptoms outside of acute episodes, clonal MCD in the absence of
      skin lesions might sometimes be difficult to identify which may lead to
      underdiagnosis, and anaphylaxis is commonly the presenting symptom in these
      patients. Although the release of mast cell (MC) mediators upon MC activation
      might present with a wide variety of symptoms, particular clinical features
      typically characterize MC mediator release episodes in patients with clonal MCD
      without skin involvement. Final diagnosis requires a bone marrow study, and it is
      recommended that this should be done in reference centers. In this article, we
      address the main triggers for anaphylaxis, risk factors, clinical presentation,
      diagnosis, and management of patients with MC activation syndromes (MCASs), with
      special emphasis on clonal MCAS [systemic mastocytosis and mono(clonal) MC
      activations syndromes].

PMID- 28740495
TI  - The Affinity of Elongated Membrane-Tethered Ligands Determines Potency of T Cell
      Receptor Triggering.
AB  - T lymphocytes are important mediators of adoptive immunity but the mechanism of T
      cell receptor (TCR) triggering remains uncertain. The interspatial distance
      between engaged T cells and antigen-presenting cells (APCs) is believed to be
      important for topological rearrangement of membrane tyrosine phosphatases and
      initiation of TCR signaling. We investigated the relationship between ligand
      topology and affinity by generating a series of artificial APCs that express
      membrane-tethered anti-CD3 scFv with different affinities (OKT3, BC3, and 2C11)
      in addition to recombinant class I and II pMHC molecules. The dimensions of
      membrane-tethered anti-CD3 and pMHC molecules were progressively increased by
      insertion of different extracellular domains. In agreement with previous studies,
      elongation of pMHC molecules or low-affinity anti-CD3 scFv caused progressive
      loss of T cell activation. However, elongation of high-affinity ligands (BC3 and
      OKT3 scFv) did not abolish TCR phosphorylation and T cell activation. Mutation of
      key amino acids in OKT3 to reduce binding affinity to CD3 resulted in restoration
      of topological dependence on T cell activation. Our results show that high
      affinity TCR ligands can effectively induce TCR triggering even at large
      interspatial distances between T cells and APCs.

PMID- 28740496
TI  - Evaluation of Antigen-Specific IgM and IgG Production during an In Vitro
      Peripheral Blood Mononuclear Cell Culture Assay.
AB  - The recent attention given to diseases associated with memory B-cell (mBC)
      produced antibodies (Abs) suggests the need for a similar in vitro assay to
      evaluate the functions of mBCs. Here, we cultured peripheral blood mononuclear
      cells (PBMCs) with the intent to collect mBC-derived Abs in vitro and maintain
      their cell-cell contact-dependent interactions with helper T-cells. PBMCs were
      cultured with interleukin (IL)-21, CpG-oligodeoxynucleotides (ODN), phorbol
      myristate acetate (PMA), and phytohemagglutinin/leucoagglutinin (PHA-L) in 24
      well flat-bottom plates (5 * 105 cells/well). A culture supernatant analysis of
      PBMCs from healthy donors (n = 10) indicated that antigen-specific IgM Ab levels
      in a PBMC culture supernatant might be better able to demonstrate the antigen
      sensitization status in a smaller peripheral blood sample, compared to IgG
      because Epstein-Barr virus-specific IgM mBCs circulate peripherally at a
      significantly higher frequency once antiviral humoral immunity has stabilized.
      Thus, our in vitro assay demonstrated the potential significance of antigen
      specific IgM Ab production in the culture supernatants. Furthermore, an analysis
      of cultured PBMCs from allograft kidney recipients (n = 16) sensitized with de
      novo donor-specific human leukocyte antigen (HLA)-specific Abs (DSAs) showed that
      IgM-type HLA-specific Abs were detected mainly from the culture supernatants from
      PBMCs of patients with stable graft function, whereas IgG isotype HLA Abs were
      detectable only from patients with biopsy-proven antibody-mediated rejection. In
      other words, these IgG isotype Abs also represented an activated humoral immune
      response in vivo. Additionally, IgM- and IgG-expressing mBCs from healthy donors
      (n = 5) were cultured with IL-21, CpG-ODN, and a supernatant produced by
      stimulating CD19+ B-cell-depleted PBMCs with PHA-L and PMA in 24-well flat-bottom
      plates (1 * 105 cells/well), and the resulting in vitro analysis provided some
      information regarding the biological processes of IgG and IgM mBCs in peripheral
      blood. Taken together, our findings suggest that antigen-specific Ab subtype
      analyses of supernatants from cultured PBMCs might more effectively and
      accurately reflect a patient's Ab-associated pathological condition vs. than
      serum IgG and IgM levels.

PMID- 28740497
TI  - The Role of Multiscale Protein Dynamics in Antigen Presentation and T Lymphocyte
      Recognition.
AB  - T lymphocytes are stimulated when they recognize short peptides bound to class I
      proteins of the major histocompatibility complex (MHC) protein, as peptide-MHC
      complexes. Due to the diversity in T-cell receptor (TCR) molecules together with
      both the peptides and MHC proteins they bind to, it has been difficult to design
      vaccines and treatments based on these interactions. Machine learning has made
      some progress in trying to predict the immunogenicity of peptide sequences in the
      context of specific MHC class I alleles but, as such approaches cannot integrate
      temporal information and lack explanatory power, their scope will always be
      limited. Here, we advocate a mechanistic description of antigen presentation and
      TCR activation which is explanatory, predictive, and quantitative, drawing on
      modeling approaches that collectively span several length and time scales, being
      capable of furnishing reliable biological descriptions that are difficult for
      experimentalists to provide. It is a form of multiscale systems biology. We
      propose the use of chemical rate equations to describe the time evolution of the
      foreign and host proteins to explain how the original proteins end up being
      presented on the cell surface as peptide fragments, while we invoke molecular
      dynamics to describe the key binding processes on the molecular level, including
      those of peptide-MHC complexes with TCRs which lie at the heart of the immune
      response. On each level, complementary methods based on machine learning are
      available, and we discuss the relationship between these divergent approaches.
      The pursuit of predictive mechanistic modeling approaches requires
      experimentalists to adapt their work so as to acquire, store, and expose data
      that can be used to verify and validate such models.

PMID- 28740498
TI  - Corrigendum: A Universal Influenza Vaccine Can Lead to Disease Exacerbation or
      Viral Control Depending on Delivery Strategies.
AB  - [This corrects the article on p. 641 in vol. 7, PMID: 28082980.].

PMID- 28740499
TI  - Multi-Omics and Integrated Network Analyses Reveal New Insights into the Systems
      Relationships between Metabolites, Structural Genes, and Transcriptional
      Regulators in Developing Grape Berries (Vitis vinifera L.) Exposed to Water
      Deficit.
AB  - Grapes are one of the major fruit crops and they are cultivated in many dry
      environments. This study comprehensively characterizes the metabolic response of
      grape berries exposed to water deficit at different developmental stages.
      Increases of proline, branched-chain amino acids, phenylpropanoids, anthocyanins,
      and free volatile organic compounds have been previously observed in grape
      berries exposed to water deficit. Integrating RNA-sequencing analysis of the
      transcriptome with large-scale analysis of central and specialized metabolites,
      we reveal that these increases occur via a coordinated regulation of key
      structural pathway genes. Water deficit-induced up-regulation of flavonoid genes
      is also coordinated with the down-regulation of many stilbene synthases and a
      consistent decrease in stilbenoid concentration. Water deficit activated both ABA
      dependent and ABA-independent signal transduction pathways by modulating the
      expression of several transcription factors. Gene-gene and gene-metabolite
      network analyses showed that water deficit-responsive transcription factors such
      as bZIPs, AP2/ERFs, MYBs, and NACs are implicated in the regulation of stress
      responsive metabolites. Enrichment of known and novel cis-regulatory elements in
      the promoters of several ripening-specific/water deficit-induced modules further
      affirms the involvement of a transcription factor cross-talk in the berry
      response to water deficit. Together, our integrated approaches show that water
      deficit-regulated gene modules are strongly linked to key fruit-quality
      metabolites and multiple signal transduction pathways may be critical to achieve
      a balance between the regulation of the stress-response and the berry ripening
      program. This study constitutes an invaluable resource for future discoveries and
      comparative studies, in grapes and other fruits, centered on reproductive tissue
      metabolism under abiotic stress.

PMID- 28740500
TI  - DNA Methylation Influences Chlorogenic Acid Biosynthesis in Lonicera japonica by
      Mediating LjbZIP8 to Regulate Phenylalanine Ammonia-Lyase 2 Expression.
AB  - The content of active compounds differ in buds and flowers of Lonicera japonica
      (FLJ) and L. japonica var. chinensis (rFLJ). Chlorogenic acid (CGAs) were major
      active compounds of L. japonica and regarded as measurements for quality
      evaluation. However, little is known concerning the formation of active compounds
      at the molecular level. We quantified the major CGAs in FLJ and rFLJ, and found
      the concentrations of CGAs were higher in the buds of rFLJ than those of FLJ.
      Further analysis of CpG methylation of CGAs biosynthesis genes showed differences
      between FLJ and rFLJ in the 5'-UTR of phenylalanine ammonia-lyase 2 (PAL2). We
      identified 11 LjbZIP proteins and 24 rLjbZIP proteins with conserved basic
      leucine zipper domains, subcellular localization, and electrophoretic mobility
      shift assay showed that the transcription factor LjbZIP8 is a nuclear-localized
      protein that specifically binds to the G-box element of the LjPAL2 5'-UTR.
      Additionally, a transactivation assay and LjbZIP8 overexpression in transgenic
      tobacco indicated that LjbZIP8 could function as a repressor of transcription.
      Finally, treatment with 5-azacytidine decreased the transcription level of LjPAL2
      and CGAs content in FLJ leaves. These results raise the possibility that DNA
      methylation might influence the recruitment of LjbZIP8, regulating PAL2
      expression level and CGAs content in L. japonica.

PMID- 28740501
TI  - HAC1 and HAF1 Histone Acetyltransferases Have Different Roles in UV-B Responses
      in Arabidopsis.
AB  - Arabidopsis has 12 histone acetyltransferases grouped in four families: the
      GNAT/HAG, the MYST/HAM, the p300/CBP/HAC and the TAFII250/HAF families. We
      previously showed that ham1 and ham2 mutants accumulated higher damaged DNA after
      UV-B exposure than WT plants. In contrast, hag3 RNA interference transgenic
      plants showed less DNA damage and lower inhibition of plant growth by UV-B, and
      increased levels of UV-B-absorbing compounds. These results demonstrated that
      HAM1, HAM2, and HAG3 participate in UV-B-induced DNA damage repair and signaling.
      In this work, to further explore the role of histone acetylation in UV-B
      responses, a putative function of other acetyltransferases of the HAC and the HAF
      families was analyzed. Neither HAC nor HAF acetyltrasferases participate in DNA
      damage and repair after UV-B radiation in Arabidopsis. Despite this, haf1 mutants
      presented lower inhibition of leaf and root growth by UV-B, with altered
      expression of E2F transcription factors. On the other hand, hac1 plants showed a
      delay in flowering time after UV-B exposure and changes in FLC and SOC1
      expression patterns. Our data indicate that HAC1 and HAF1 have crucial roles for
      in UV-B signaling, confirming that, directly or indirectly, both enzymes also
      have a role in UV-B responses.

PMID- 28740502
TI  - The AMP-Activated Protein Kinase KIN10 Is Involved in the Regulation of Autophagy
      in Arabidopsis.
AB  - Autophagy is a highly conserved system in eukaryotes for the bulk degradation and
      recycling of intracellular components. Autophagy is involved in many
      physiological processes including development, senescence, and responses to
      abiotic and biotic stress. The adenosine 5'-monophosphate (AMP)-activated protein
      kinase AMPK positively regulates autophagy in mammals; however, the potential
      function of AMPK in plant autophagy remains largely unknown. Here, we identified
      KIN10, a plant ortholog of the mammalian AMPK, as a positive regulator of plant
      autophagy and showed that it acts by affecting the phosphorylation of ATG1
      (AUTOPHAGY-RELATED GENE 1) proteins in Arabidopsis. Transgenic Arabidopsis lines
      overexpressing KIN10 (KIN10-OE) showed delays in leaf senescence, and increased
      tolerance to nutrient starvation, these phenotypes required a functional
      autophagy pathway. Consistent with KIN10 having a potential role in autophagy,
      the nutrient starvation-induced formation of autophagosomes and cleavage of GFP
      ATG8e were accelerated in the KIN10-OE lines compared to the wild type. Moreover,
      the KIN10-OE lines were less sensitive to drought and hypoxia treatments,
      compared with wild type. Carbon starvation enhanced the level of phosphorylated
      YFP-ATG1a in the KIN10-OE lines compared to that of wild type. Together, these
      findings suggest that KIN10 is involved in positive regulation of autophagy,
      possibly by affecting the phosphorylation of ATG1s in Arabidopsis.

PMID- 28740503
TI  - Interaction of 2,4-D or Dicamba with Glufosinate for Control of Glyphosate
      Resistant Giant Ragweed (Ambrosia trifida L.) in Glufosinate-Resistant Maize (Zea
      mays L.).
AB  - Glyphosate-resistant (GR) giant ragweed is a problematic broadleaf weed in crops
      including maize and soybean in the Midwestern United States. Commercialization of
      crops with 2,4-D or dicamba and glufosinate resistance will allow post-emergence
      (POST) applications of these herbicides. Therefore, information is needed on how
      2,4-D/dicamba will interact with glufosinate in various rate combinations. The
      objectives of this study were to evaluate the interaction of glufosinate plus 2,4
      D and/or dicamba for control of GR giant ragweed, and to determine their effect
      on GR giant ragweed density, biomass, maize injury, and yield. Field experiments
      were conducted in 2013 and 2014 in a field infested with GR giant ragweed in
      Nebraska, United States. The treatments included POST applications of glufosinate
      (450 or 590 g ai ha-1), 2,4-D, or dicamba at 280 or 560 g ae ha-1 applied alone
      and in tank-mixtures in glufosinate-resistant maize. The results showed that
      dicamba applied alone resulted in 56 to 62% and 73 to 83% control at 14 and 28
      days after treatment (DAT), respectively, and >=95% control at 60 DAT or at
      harvest compared to 17 to 30% and 57 to 73% control with 2,4-D applied alone at
      280 and 560 g ai ha-1, respectively. Glufosinate tank-mixed with 2,4-D and/or
      dicamba consistently provided >=89% control of GR giant ragweed, except that
      control with glufosinate plus 2,4-D varied from 80 to 92% at 60 DAT and at
      harvest. The comparison between the observed and expected control (determined by
      Colby's equation) suggested an additive interaction between glufosinate and 2,4-D
      or dicamba for control of GR giant ragweed. Contrast analysis also indicated that
      GR giant ragweed control with glufosinate plus 2,4-D or dicamba was either
      consistently higher or comparable with individual herbicides excluding 2,4-D
      applied alone. Herbicide programs, excluding 2,4-D at 280 g ae ha-1, resulted in
      >=80% reduction in GR giant ragweed density. Tank-mixing glufosinate with 2,4-D
      or dicamba showed an additive effect and will be an additional tool with two
      effective modes of action for the management of GR giant ragweed in maize.

PMID- 28740504
TI  - 2,4-Thiazolidinedione Treatment Improves the Innate Immune Response in Dairy
      Goats with Induced Subclinical Mastitis.
AB  - Mastitis is a major disease in dairy cows resulting in significant economic
      losses. In vitro works suggest that ruminants peroxisome proliferator-activated
      receptor gamma (PPARgamma) can aid in improving the response to mastitis and can
      control milk fat synthesis. The objectives of the present experiment were to test
      if treatment with the putative PPARgamma agonist 2,4-thiazolidinedione (TZD)
      improves (1) the response to subclinical mastitis and (2) milk fat production.
      Lactating goats received daily injections of 8 mg/kg BW of TZD or saline for 3
      weeks. After one week of TZD injection, half of the goats in each group received
      intramammary infusion of Strep. uberis or saline in both halves for a total of 4
      groups (n = 6/group). TZD treatment did not affect milk fat but had positive
      effect on milk somatic cells count, blood nonesterified fatty acids, inflammatory
      markers, and liver function. TZD significantly increased myeloperoxidase but did
      not affect leukocytes phagocytosis or insulin. TZD increased adipocytes size and
      had minor effect on expression of PPARgamma target genes in mammary epithelial
      cells but not in adipose tissue. Overall, TZD ameliorated the response to
      intramammary infection but the effect on milk fat synthesis and expression of
      related transcripts was less than expected.

PMID- 28740505
TI  - Object Extraction in Cluttered Environments via a P300-Based IFCE.
AB  - One of the fundamental issues for robot navigation is to extract an object of
      interest from an image. The biggest challenges for extracting objects of interest
      are how to use a machine to model the objects in which a human is interested and
      extract them quickly and reliably under varying illumination conditions. This
      article develops a novel method for segmenting an object of interest in a
      cluttered environment by combining a P300-based brain computer interface (BCI)
      and an improved fuzzy color extractor (IFCE). The induced P300 potential
      identifies the corresponding region of interest and obtains the target of
      interest for the IFCE. The classification results not only represent the human
      mind but also deliver the associated seed pixel and fuzzy parameters to extract
      the specific objects in which the human is interested. Then, the IFCE is used to
      extract the corresponding objects. The results show that the IFCE delivers better
      performance than the BP network or the traditional FCE. The use of a P300-based
      IFCE provides a reliable solution for assisting a computer in identifying an
      object of interest within images taken under varying illumination intensities.

PMID- 28740506
TI  - Comparison of Inflammation-Based Prognostic Scores in a Cohort of Patients with
      Resectable Esophageal Cancer.
AB  - BACKGROUND: A number of studies have revealed that inflammation-based prognostic
      scores, such as Glasgow prognostic score (GPS), modified Glasgow prognostic score
      (mGPS), and C-reactive protein and albumin ratio (C/A ratio), are associated with
      poor outcome in cancer patients. However, until now, no study has investigated
      the role of these prognostic scores in a cohort of neoadjuvant-treated esophageal
      adenocarcinomas (nEAC) and squamous cell carcinomas (nESCC). METHODS: Patients
      had laboratory measurements within three days before resection. GPS, mGPS, and
      C/A ratio were tested together with established clinicopathological factors in
      simple and multiple Cox regression analysis of overall survival (OS) and disease
      free survival (DFS). RESULTS: A total of 283 patients (201 EAC and 82 ESCC) with
      locally advanced esophageal cancer were enrolled. 167 patients received
      neoadjuvant treatment (59.0%). Simple analysis revealed that there were
      significant differences in cancer-specific survival in relation to elevated C
      reactive protein (p = 0.011), lymph node status (p < 0.001), UICC stage (p <
      0.001), and nEAC (p = 0.005). mGPS (p = 0.024) showed statistical significance in
      simple analysis. No statistical significance could be found for GPS (p = 0.29),
      mGPS (p = 0.16), and C/A ratio (p = 0.76) in multiple analysis. CONCLUSION: The
      investigated prognostic scores should be used and interpreted carefully, and
      established factors like histology, including tumor size and differentiation,
      lymph node involvement, and status of resection margin remain the only reliable
      prognostic factors for patients suffering from resectable EC.

PMID- 28740508
TI  - Hydrogen Sulfide Inhibits High Glucose-Induced sFlt-1 Production via Decreasing
      ADAM17 Expression in 3T3-L1 Adipocytes.
AB  - Hydrogen sulfide (H2S) has recently been identified as an endogenous gaseous
      signaling molecule. The aim of the present study was to investigate the effect of
      H2S on high glucose- (HG-) induced ADAM17 expression and sFlt-1 production in 3T3
      L1 adipocytes. Firstly, we found that HG DMEM upregulated the expression of
      ADAM17 and production of sFlt-1 in 3T3-L1 adipocytes. Knocking down ADAM17
      attenuated the effect of high glucose on sFlt-1 production in adipocytes. HG
      decreased the expression of CSE and 3-MST, as well as the endogenous H2S
      production. Furthermore, knocking down CSE and 3-MST significantly increased
      ADAM17 expression and sFlt-1 production. The addition of exogenous H2S through
      the administration of sodium hydrosulfide (NaHS) inhibited HG-induced
      upregulation of ADAM17 expression and sFlt-1 production. In conclusion, decreased
      expression of CSE and 3-MST and the subsequent decrease in H2S production
      contribute to high glucose-induced sFlt-1 production via activating ADAM17 in
      adipocytes. Exogenous H2S donor NaHS has a potential therapeutic value for
      diabetic vascular complications.

PMID- 28740507
TI  - MiR-195 Inhibits Tumor Growth and Metastasis in Papillary Thyroid Carcinoma Cell
      Lines by Targeting CCND1 and FGF2.
AB  - BACKGROUND: MicroRNA (miRNA) dysregulation was commonly seen in papillary thyroid
      carcinoma (PTC), and miR-195 was verified to be downregulated in PTC by the large
      data set analysis from The Cancer Genome Atlas (TCGA). Our study aimed to explore
      the biological functions and the underlying molecular mechanisms of miR-195 in
      PTC. METHODS: The relative expression of miR-195 and its target genes were
      assessed by quantitative RT-PCR assay in 38 pairs of PTC and the adjacent thyroid
      tissues. Assays were performed to evaluate the effect of miR-195 on the
      proliferation, migration, and invasion in PTC cell lines. Moreover, we searched
      for targets of miR-195 and explored the possible molecular pathway of miR-195 in
      PTC. RESULTS: We found that miR-195 was downregulated in PTC cell lines and
      tissues. Overexpression of miR-195 significantly inhibited cell proliferation,
      migration, and invasion in K1 and BCPAP cell lines. CCND1 and FGF2, which had
      inverse correlations with miR-195 in clinical specimens, were found to be the
      direct targets of miR-195. Furthermore, miR-195 might be involved in PTC
      tumorigenesis by suppressing the Wnt/beta-catenin signaling pathway. CONCLUSIONS:
      These results highlight an important role of miR-195 in the initiation and
      progression of PTC and implicate the potential application of miR-195 in PTC
      target therapy.

PMID- 28740509
TI  - Multiple Bony Injuries on Bone Scan in a Case of Unsuspected Child Abuse.
AB  - This case is described of an eleven-month-old infant with lower limbs swelling
      and the left elbow skeletal malformation following a fall. The radionuclide bone
      scan was performed to exclude bone infection or congenital skeletal anomaly. The
      images unexpectedly showed multiple increased radioactive foci throughout the
      whole body. It was a strong probability of child abuse. All lesions are readily
      apparent on the following plain film radiographs and MRI.

PMID- 28740510
TI  - Hematopoietic Stem Cell Transplantation: A Bioethical Lens.
AB  - Hematopoietic stem cell transplantation (HSCT) is one of a range of therapeutic
      options available to patients suffering from various diseases. HSCT procedure
      involves important ethical and legal aspects that can occur at every phase of the
      procedure: the clinical choice of whether to perform the procedure,
      pretransplantation preparation regimens, donor selection, stem cell harvest
      procedure, transplantation phase, and short-term and long-term follow-up care. In
      this discussion paper, we outline the ethical issue-facing physicians involved in
      HSCT. Currently, HSCT is a widely accepted treatment for many life-threatening
      diseases. It thus represents a real therapeutic hope for many patients. It does,
      however, carry a burden of possible morbidity and mortality. Consequently, there
      are substantial information and communication issues involved in the consent
      process for HSCT. In the final decision, the judgements of different parties,
      such as patients, family members, and healthcare professionals, intersect and
      overlap and this is particularly true when the patient is a minor. Finally, HSCT
      is a very expensive procedure. The social and economic concerns of HSCT are
      discussed within the actual contextual framework of the dramatic increase in
      healthcare costs and inequalities in healthcare in relation to socioeconomic
      status, educational status, and ethnicity.

PMID- 28740511
TI  - Safety and Tolerance of Donor-Derived Mesenchymal Stem Cells in Pediatric Living
      Donor Liver Transplantation: The MYSTEP1 Study.
AB  - BACKGROUND: Calcineurin inhibitors (CNI) have significantly improved patient and
      graft survival in pediatric liver transplantation (pLT). However, CNI toxicity
      leads to significant morbidity. Moreover, CNIs cannot prevent long-term allograft
      injury. Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory
      properties, which may promote allograft tolerance and ameliorate toxicity of high
      dose CNI. The MYSTEP1 trial aims to investigate safety and feasibility of donor
      derived MSCs in pLT. METHODS/DESIGN: 7 to 10 children undergoing living-donor pLT
      will be included in this open-label, prospective pilot trial. A dose of 1 * 106
      MSCs/kg body weight will be given at two time points: first by intraportal
      infusion intraoperatively and second by intravenous infusion on postoperative day
      2. In addition, participants will receive standard immunosuppressive treatment.
      Our primary objective is to assess the safety of intraportal and intravenous MSC
      infusion in pLT recipients. Our secondary objective is to evaluate efficacy of
      MSC treatment as measured by the individual need for immunosuppression and the
      incidence of biopsy-proven acute rejection. We will perform detailed immune
      monitoring to investigate immunomodulatory effects. DISCUSSION: Our study will
      provide information on the safety of donor-derived MSCs in pediatric living-donor
      liver transplantation and their effect on immunomodulation and graft survival.

PMID- 28740512
TI  - Mesenchymal Stem Cells as Promoters, Enhancers, and Playmakers of the
      Translational Regenerative Medicine.

PMID- 28740513
TI  - IGF-1 Gene Transfer to Human Synovial MSCs Promotes Their Chondrogenic
      Differentiation Potential without Induction of the Hypertrophic Phenotype.
AB  - Mesenchymal stem cell- (MSC-) based therapy is a promising treatment for
      cartilage. However, repair tissue in general fails to regenerate an original
      hyaline-like tissue. In this study, we focused on increasing the expression
      levels for insulin-like growth factor-1 (IGF-1) to improve repair tissue quality.
      The IGF-1 gene was introduced into human synovial MSCs with a lentiviral vector
      and examined the levels of gene expression and morphological status of MSCs under
      chondrogenic differentiation condition using pellet cultures. The size of the
      pellets derived from IGF-1-MSCs were significantly larger than those of the
      control group. The abundance of glycosaminoglycan (GAG) was also significantly
      higher in the IGF-1-MSC group. The histology of the IGF-1-induced pellets
      demonstrated similarities to hyaline cartilage without exhibiting features of a
      hypertrophic chondrocyte phenotype. Expression levels for the Col2A1 gene and
      protein were significantly higher in the IGF-1 pellets than in the control
      pellets, but expression levels for Col10, MMP-13, ALP, and Osterix were not
      higher. Thus, IGF-1 gene transfer to human synovial MSCs led to an improved
      chondrogenic differentiation capacity without the detectable induction of a
      hypertrophic or osteogenic phenotype.

PMID- 28740514
TI  - Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix
      Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and
      Commitment.
AB  - Human resident cardiac progenitor cells (CPCs) isolated as cardiosphere-derived
      cells (CDCs) are under clinical evaluation as a therapeutic product for cardiac
      regenerative medicine. Unfortunately, limited engraftment and differentiation
      potential of transplanted cells significantly hamper therapeutic success.
      Moreover, maladaptive remodelling of the extracellular matrix (ECM) during heart
      failure progression provides impaired biological and mechanical signals to
      cardiac cells, including CPCs. In this study, we aimed at investigating the
      differential effect on the phenotype of human CDCs of cardiac fibroblast-derived
      ECM substrates from healthy or diseased hearts, named, respectively, normal or
      pathological cardiogel (CG-N/P). After 7 days of culture, results show increased
      levels of cardiogenic gene expression (NKX2.5, CX43) on both decellularized
      cardiogels compared to control, while the proportion and staining patterns of
      GATA4, OCT4, NKX2.5, ACTA1, VIM, and CD90-positive CPCs were not affected, as
      assessed by immunofluorescence microscopy and flow cytometry analyses.
      Nonetheless, CDCs cultured on CG-N secreted significantly higher levels of
      osteopontin, FGF6, FGF7, NT-3, IGFBP4, and TIMP-2 compared to those cultured on
      CG-P, suggesting overall a reduced trophic and antiremodelling paracrine profile
      of CDCs when in contact with ECM from pathological cardiac fibroblasts. These
      results provide novel insights into the bidirectional interplay between cardiac
      ECM and CPCs, potentially affecting CPC biology and regenerative potential.

PMID- 28740515
TI  - In Vivo Tracking of Chemokine Receptor CXCR4-Engineered Mesenchymal Stem Cell
      Migration by Optical Molecular Imaging.
AB  - CXCR4, the stromal cell-derived factor-1 receptor, plays an important role in the
      migration of hematopoietic progenitor/stem cells to injured and inflamed areas.
      Noninvasive cell tracking methods could be useful for monitoring cell fate.
      Therefore, in this study, we evaluated the efficacy of an intravenous infusion of
      genetically engineered mesenchymal stem cells (MSCs) overexpressing CXC chemokine
      receptor 4 (CXCR4) to home to the tumor, by optical imaging. We constructed a
      retroviral vector containing CXCR with dual reporter genes, eGFP and Fluc2, under
      the control of an EF1alpha promoter (pBABE-EF1alpha-CXCR4-eGFP-IRES-Fluc2). We
      also developed an eGFP-Fluc2 construct in the Retro-X retroviral vector (Retro-X
      eGFP-Fluc2). MSCs were transduced with retroviruses to generate CXCR4
      overexpressing MSCs (MSC-CXCR4/Fluc2) and MSCs (MSC/Fluc2). CXCR4 mRNA and
      protein expression was confirmed by RT-PCR and Western blotting, respectively,
      and it was higher in MSC-CXCR4/Fluc2 than in naive MSCs. eGFP expression was
      confirmed by confocal microscopy. The transfected MSC-CXCR4/Fluc2 cells showed
      higher migratory capacity than naive MSCs observed in Transwell migration assay.
      The in vivo migration of CXCR4-overexpressing MSCs to MDAMB231/Rluc tumor model
      by BLI imaging was also confirmed. Intravenous delivery of genetically modified
      MSCs overexpressing CXCR4 with a Fluc2 reporter gene may be a useful, noninvasive
      BLI imaging tool for tracking cell fate.

PMID- 28740516
TI  - PGE2 Promotes the Migration of Mesenchymal Stem Cells through the Activation of
      FAK and ERK1/2 Pathway.
AB  - A critical step of MSCs therapy is dependent on its ability to migrate into the
      sites of injury, so various approaches have been introduced to boost the
      migratory ability of MSCs. PGE2 is the major prostaglandin generated by COX
      enzymes and has been implicated in inflammatory response. Evidence indicates that
      PGE2 can facilitate MSCs migration. Further exploration of the underlying
      molecular mechanism participating in the promigratory ability of PGE2 may provide
      a novel strategy to improve MSC transplantation efficacy. In this study, our
      findings suggested that EP2 prostanoid receptor promotes MSCs migration through
      activation of FAK and ERK1/2 pathways. Furthermore, MSCs migration induced by
      PGE2 was blunted by FAK or ERK1/2 inhibitors. EP2-mediated MSCs migration depends
      on the activation of FAK and ERK1/2. However, the current study did not
      investigate the migration of MSCs over a blood vessel endothelial barrier. In
      conclusion, our findings reveal EP2-mediated FAK and ERK1/2 activation was
      essential for MSCs migration induced by PGE2, indicating that activation of EP2
      receptor and FAK/ERK pathways may be a promising strategy to accelerate homing
      efficiency of MSCs, which in turn enhances therapeutic potential of MSCs
      transplantation.

PMID- 28740517
TI  - Dengue Virus NS1 Protein as a Diagnostic Marker: Commercially Available ELISA and
      Comparison to qRT-PCR and Serological Diagnostic Assays Currently Used by the
      State of Florida.
AB  - BACKGROUND: The proper management of patients infected with dengue virus requires
      early detection. Here, real-time molecular assays have proven useful but have
      limitations, whereas ELISAs that detect antibodies are still favored but results
      are obtained too late to be of clinical value. The production of DENV NS1 peaks
      early during infection and its detection can combine the advantages of both
      diagnostic approaches. METHODS: This study compared assays currently used for
      detecting DENV infection at the Florida Department of Health including anti-DENV
      IgM and IgG ELISAs as well as qRT-PCR, against a commercially available DENV NS1
      ELISA. These comparisons were made among a group of 21 human sera. RESULTS: Nine
      of 14 (64.3%) DENV qRT-PCR+ samples were also DENV NS1+. Interestingly, the 5 NS1
      samples that were qRT-PCR+ were additionally IgM- and IgG+ suggesting a
      nonprimary infection. Compared to qRT-PCR, the NS1 assay had a sensitivity of
      64.3%, specificity 100%, PPV of 100%, and NPV of 58.3%. CONCLUSIONS: The NS1
      ELISA performed as expected in known DENV qRT-PCR+ samples; however negative NS1
      results for qRT-PCR+ and IgG+ sera seemingly reduced the usefulness of the NS1
      ELISA for nonprimary cases. We therefore conclude that diagnosis obtained via
      DENV NS1 ELISA deserves further investigation.

PMID- 28740518
TI  - From the Editor-in-Chief.

PMID- 28740519
TI  - Low-dose diclofenac in patients with fragility fractures.
AB  - Most osteoporotic patients complain of back pain one year after a fragility
      vertebral fracture and the frequency of chronic back pain increases with
      increasing age. The use of the lowest effective dose of an analgesic which is
      able to control symptoms seems to be a possible solution in order to limit
      potential side effects in multi-treated elderly patients. Non-steroidal anti
      inflammatory drugs (NSAIDs) have a proven efficacy in the treatment of back pain
      associated with fragility vertebral fractures and diclofenac is available at low
      dose subcutaneous injective formulation. This is the rational of ImPAVeDic study,
      acronym of Improvement of back Pain Associated with fragility Vertebral fractures
      with low-dose Diclofenac, an observational study that will be performed in a
      group of 50 elderly (>= 65 years), male and female osteoporotic patients with
      symptomatic fragility vertebral fractures. The objective of the study is to
      evaluate the improvement of back pain in the study population treated with low
      dose diclofenac and regularly monitored for 2-6 months. Visual Analogic Scale
      (VAS) and Numerical Rating Scale (NRS) will be used for pain monitoring. The
      reduction of the risk of occurrence of drug side effects can favour the
      optimization of elderly patients' care.

PMID- 28740520
TI  - Vitamin D levels and their impact on mineral metabolism in HIV infected patients:
      an exploratory study.
AB  - : Vitamin D has immunomodulating properties. The nuclear receptor for vitamin D
      is expressed in several immune cells, which convert 25-hydroxyvitamin D (25OHD)
      to the active form 1,25 hydroxyvitamin D [1,25(OH)2 D]. Under conditions of
      infection, 1,25(OH)2 D promotes production of cathelicidin (an antimicrobial
      peptide) in monocytes and activated macrophages. In vitro studies have shown the
      ability of cathelicidin to inhibit replication of human immunodeficiency virus
      (HIV-1) in T CD4 lymphocytes and macrophages. OBJECTIVE: To evaluate vitamin D
      levels and their impact on mineral metabolism in HIV infected patients. MATERIALS
      AND METHODS: Seventy-four clinical records of HIV/AIDS patients seen at the
      outpatients clinic were reviewed. The following data were collected: age, sex,
      time since diagnosis of HIV, HIV-1 viral load, CD4 counts (absolute value and
      percentage), and mineral metabolism determinations: 25OHD, intact parathormone
      (iPTH); serum calcium (sCa); serum phosphorus (sP) and serum crosslaps (sCTX).
      Vitamin D levels were stratified as follows: optimal: >=30ng/ml; insufficient: 21
      29ng/ml; moderately deficient: 20>= -25OHD- >10 ng/ml and severely deficient <=10
      ng/ml. RESULTS: Fifty-five clinical records were included; 82% of patients had
      25OHD levels below 30ng/ml (insufficient: 23.6%, moderately deficient: 36.4%; and
      severely deficient: 21.8%). A significantly higher serum PTH levels in the
      moderately and severely deficient groups than in the optimal and insufficient
      groups was observed (p<0.05 and p<0.03 respectively). A weak negative correlation
      was observed between serum 25OHD and PTH levels (r=-0.268; p<0.004). CONCLUSION:
      Sub-optimal vitamin D levels are frequently observed in HIV/AIDS patients on
      antiretroviral therapy (ART). Systematic assessment of mineral metabolism is
      considered necessary in HIV/AIDS positive patients.

PMID- 28740521
TI  - New quantitative ultrasound techniques for bone analysis at the distal radius in
      hip fracture cases: differences between femoral neck and trochanteric fractures.
AB  - BACKGROUND: Ample evidence on etiological and pathological differences between
      femoral neck and trochanteric fracture cases suggests the possibility of
      individualized treatment. There are many issues related to areal bone mineral
      density and other quantitative computed tomography parameters of the proximal
      femur. Although osteoporosis is a systemic problem, little has been reported
      regarding differences in bone structural parameters, including bone mineral
      density, between them in regions other than the proximal femur. METHODS:
      Participants were consecutive female patients >50 years of age admitted to the
      Saiseikai Suita Hospital (Osaka prefecture, Japan) for their first hip fracture
      between January 2012 and September 2014. Cortical thickness (CoTh, mm),
      volumetric trabecular bone mineral density (TBD, mg/cm3), and elastic modulus of
      trabecular bone (EMTb, GPa) were obtained as the new QUS parameters using the LD
      100 system (Oyo Electric, Kyoto, Japan). The mean values of these parameters were
      compared between femoral neck and trochanteric fracture cases. In addition,
      correlations between age and each QUS parameter were investigated for each
      fracture type. A receiver operating characteristic (ROC) curve analysis was
      performed to examine the degree of effect each parameter on the fracture types.
      The area under the curve (AUC) for each parameter was compared to the AUC for
      age. RESULTS: There were 63 cases of femoral neck fracture (mean age, 78.2 years)
      and 37 cases of trochanteric fracture (mean age, 85.9 years). Mean TBD and EMTb
      were significantly higher for femoral neck fractures. There were significant
      negative correlations between QUS parameters and age for femoral neck fractures
      (P < 0.005). The regression lines for femoral neck fractures were above those for
      trochanteric fractures for TBD and EMTb. AUCs were 0.72 for age, and 0.61, 0.65,
      and 0.65 for CoTh, TBD, and EMTb, respectively. CONCLUSIONS: The new QUS
      parameters indicated that TR fracture cases were more osteoporotic than were FN
      fracture cases, even at the distal radius. There might be systemic differences
      between them, in addition to localized factors at the proximal femur.

PMID- 28740522
TI  - Use of teriparatide off-label: our experience and review of literature.
AB  - The aim of this paper is to report our experience and to present a review of
      literature about the use of teriparatide off-label in the therapy of non-unions.
      Teriparatide is used exclusively in treatment of osteoporosis and to prevent bone
      fracture because it has a positive effect on bone strength and architecture. The
      use of teriparatide in non-unions is described as effective in numerous case
      report.

PMID- 28740523
TI  - The effects of zoledronic acid on ECG: a prospective study on patients with bone
      metastatic cancer.
AB  - INTRODUCTION: There are controversial results in the risk of atrial fibrillation
      as well as arrhythmogenic potential of bis-phosphonates. METHOD: 37 patients and
      40 healthy controls were evaluated prospectively with regard to the cardiac side
      effects related to the use of zoledronic acid (ZA) and its effects on
      electrocardiography (ECG) parameters. RESULT: As the basal ECG results of the
      patients diagnosed with cancer compared with the control group, it was determined
      that QT maximum was significantly lower, QT minimum was significantly higher.
      However; it was determined that QT disp, P max, P min, and P disp values were not
      significantly different. There was no statistically significant difference in P
      max, P min, P disp, QT max, QT min, QT disp values of the ECG parameters measured
      from cancer patients, before and 60 minutes after ZA therapy. CONCLUSION: There
      were no significant alterations in ECG in the acute period, indicated that ZA had
      no arrhythmia potential in the early period in patients with no underlying
      cardiac disease. However: patients receiving ZA should be monitored more closely
      because of the risk of arrhythmia which may ensue due to hypocalcemia,
      hypomagnesemia, or other chemotherapeutics.

PMID- 28740524
TI  - A comparison of two fixation methods for femoral trochanteric fractures: a new
      generation intramedullary system vs sliding hip screw.
AB  - INTRODUCTION: Trochanteric fractures are frequent and generally associated with
      bone fragility. There is still debate on the best fixation device to treat stable
      or rather stable trochanteric fractures: we report our clinical and radiological
      results of fixation with Proximal Femoral Nail "antirotation" (PFNa) in a
      population of patients compared to a control group treated by Sliding Hip Screw
      (SHS). MATERIALS AND METHODS: A prospective study was conducted in 71 consecutive
      patients treated by PFNa (group A), and 69 by a SHS (group B), with a mean age of
      81.6 and 83.4 years respectively. Short Form 12 was administered to check
      postoperative results, and the following parameters were evaluated: range of
      motion, evaluation of pain, gait ability, X-rays, and Tip Apex Distance Index.
      RESULTS: A minimum follow-up was conducted in 128 patients: 66 subjects belonging
      to the PFNa group and 62 to the DHS group. All patients in the group A were able
      to reach partial or full weight-bearing on the operated leg before leaving the
      hospital. Forty-four patients (63.8%) of the group B were able to walk with
      partial weight-bearing before discharge. We recorded 17 complications with a
      final overall percentage of 17.2% on the overall study population with one single
      case of failure in both the two groups. DISCUSSION: A statistical significance
      (p<0.01) of superiority for PFNa was demonstrated regarding surgical time,
      amplioscope time, intraoperative blood loss, hospital stay, recovery of weight
      bearing before discharge. Less significant results (p<0.05) were found for
      walking ability at the three-months follow-up and patients' satisfaction 6 months
      after surgery. CONCLUSIONS: PFNa may be considered an useful choice for the
      treatment of stable or rather stable trochanteric fractures as well as DHS. The
      light superiority of PFNa may be principally related to its mechanical
      advantages.

PMID- 28740525
TI  - The use of cholecalciferol in patients with hip fracture.
AB  - INTRODUCTION: Major osteoporotic fractures are steadily increasing due to
      population aging. Programs of secondary prevention against refracture are
      essential to decrease morbidity and mortality and the cost for individuals and
      the society. Vitamin D supplementation and optimization of calcium intake are of
      a pivotal importance to start specific osteoporosis treatment and for its safety
      and efficacy. Cholecalciferol is the most widely employed drug for vitamin D
      supplementation. PURPOSE: Aim of this study was to assess the trends in the use
      of vitamin D supplements containing cholecalciferol in the population of hip
      fracture patients older than 65 years, resident in the region of Tuscany (Italy)
      in the years 2011-2015 and to describe vitamin D status in a subgroup of this
      individuals directly referred to a bone clinic for further evaluation after hip
      osteoporotic fracture. METHODS: Data were retrieved from the electronic anonymous
      regional administrative database administered by the Region of Tuscany (Italy) in
      the years 2011-2015 within the T.A.R.Ge.T. project (Trattamento Appropriato delle
      Rifratture Geriatriche in Toscana, i.e., "Appropriate treatment of geriatric
      refractures in Tuscany"), a program endorsed by the region itself. Data
      pertaining to cholecalciferol prescriptions and hospital discharge codes were
      retrieved and appropriately crossed to get data on the use of cholecalciferol
      supplements in patients before and after a hip fracture. A retrospective analysis
      was carried out in a subgroup of subjects (n 254) appropriately referred to the
      local fracture liaison service after the major osteoporotic fracture and vitamin
      D status in terms of serum 25(OH) vitamin D levels was assessed. RESULTS: The
      majority of subjects experiencing a hip fracture (98.2% and 88.3% in 2011 and
      2015, respectively) did not receive vitamin D supplements at the time of the
      fracture event. Although a trend in increase in prescriptions for cholecalciferol
      supplements could be observed in the years of the study, the percentage of
      treated individuals remained low even after the fracture, since only 30-35% of
      subjects receives cholecalciferol supplements at one year after the fracture.
      Cholecalciferol remained the most prescribed drug in this population, while a
      substantial decrease of cholecalciferol in association with calcium salts was
      observed. The use of high doses of cholecalciferol has decreased in this
      population, while diminished the use of the drops has been accompanied by an
      increase in prescriptions of single monthly dose supplements. CONCLUSIONS: The
      correction of vitamin D inadequacy is preliminary to any treatment for
      osteoporosis and together with calcium may reduce fracture risk by itself. The
      prescription of vitamin D supplements is low in patients before and after a hip
      fracture in a Mediterranean region and despite the overall increase in vitamin
      use and abuse in the general population. Proper educational programs and active
      fracture liaison services are needed in order to bridge this gap.

PMID- 28740526
TI  - Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT.
AB  - INTRODUCTION: Complex regional pain syndrome (CRPS) is a major complication after
      trauma, surgery, and/or immobilization of an extremity. The disease often starts
      with clinical signs of local inflammation and develops into a prolonged phase
      that is characterized by trophic changes and local osteoporosis and sometimes
      results in functional impairment of the affected limb. While the pathophysiology
      of CRPS remains poorly understood, increased local bone resorption plays an
      undisputed pivotal role. The aim of this retrospective clinical study was to
      assess the bone microstructure in patients with CRPS. METHODS: Patients with CRPS
      type I of the upper limb whose affected and unaffected distal radii were analyzed
      by high-resolution peripheral quantitative computed tomography (HR-pQCT) were
      identified retrospectively. The osteology laboratory data and dual-energy X-ray
      absorptiometry (DXA) images of the left femoral neck and lumbar spine, which were
      obtained on the same day as HR-pQCT, were extracted from the medical records.
      RESULTS: Five patients were identified. The CRPS-affected upper limbs had
      significantly lower trabecular numbers and higher trabecular thicknesses than the
      unaffected upper limbs. However, the trabecular bone volume to total bone volume
      and cortical thickness values of the affected and unaffected sides were similar.
      Trabecular thickness tended to increase with time since disease diagnosis.
      DISCUSSION: CRPS associated with significant alterations in the bone
      microstructure of the affected upper limb that may amplify as the duration of
      disease increases.

PMID- 28740527
TI  - Molecular genetics in primary hyperparathyroidism: the role of genetic tests in
      differential diagnosis, disease prevention strategy, and therapeutic planning. A
      2017 update.
AB  - Primary hyperparathyroidism (PHPT) is one of the most frequent endocrine disease
      in developed countries. It mainly occurs as sporadic cases (about 90-95% of
      cases), while only the remaining 5-10% is represented by familial inherited
      parathyroid disorders due to causative mutations in specific target genes.
      Clinical variability among the different familial parathyroid syndromes is
      generally linked to the specific mutated gene and it can predispose subjects to
      different manifestations of parathyroid pathology, various degrees of PHPT
      severity, persistence and/or after-surgery recurrences. Genetic tests is helpful
      in differential diagnosis favouring the recognition of the specific familial PHPT
      syndrome and, subsequently, in planning the most suitable surgical procedures
      and/or pharmacological interventions. Moreover, genetic test is important to
      recognise mutation carriers, within PHPT familial forms, even before the
      appearance of biochemical and/or clinical symptoms. This review resumes general
      concepts about genetic diagnosis of PHPT in familial hereditary syndromes,
      specifically describing why, when, and which genetic screenings should be
      performed in every specific PHPT-associated parathyroid disease.

PMID- 28740528
TI  - Bone health in menopausal women: a role for General Practitioners.
AB  - General Practitioners (GPs) are in a prime location to assess patient health
      needs, knowing clinical history, living habits and risk factors. GPs can identify
      in healthy people those in which prevention could be useful, in order to avoid or
      delay some diseases. For this purpose GPs need to change their care model from a
      waiting model to a proactive model, in order to identify health needs before the
      development of diseases.

PMID- 28740529
TI  - Legg-Calve-Perthes disease: classifications and prognostic factors.
AB  - INTRODUCTION: Legg-Calve-Perthes Disease (LCPD) represents idiopathic avascular
      necrosis of femoral head in pediatric population. Indications for treatment
      depend mostly on prognosis about femoral head sphericity and hip congruence at
      the end of growth. The aim of this review is to highline prognostic factors of
      LCPD. METHODS: Bibliographic search in PubMed allowed selection of 33 articles
      concerning prognostic factors and/or classification of LCPD. CONCLUSION: Clinical
      factors of poor prognosis are overweight, female sex, age exceeding 6 years old,
      and lack of hip abduction. Radiologically, Herring's classification is consensual
      because of its high prognostic value and very good reproducibility. The other
      signs of femoral head "at-risk" and the assessment of the reduction in abduction
      of the femoral head in the acetabulum are also prognostic of late evolution. MRI
      seems to be a future tool in assessing the fate of hips in LCPD. It is likely
      that a better understanding of LCPD etiology would precise the prognosis of this
      disease.

PMID- 28740530
TI  - Transient osteoporosis of the hip with a contralateral delayed involvement: a
      case report.
AB  - We describe a case of non-simultaneous bilateral hip pain with bone marrow edema
      occurring in an adult male, with the contralateral hip being involved 12 years
      later after the onset of symptoms. On the basis of clinical and imaging findings,
      together with a complete resolution after conservative management, a post-hoc
      diagnosis of metachronous bilateral transient osteoporosis of the hip (TOH) was
      made. Non-simultaneous bilateral presentation of TOH is exceptional, and
      contralateral involvement with a 12-year delay has never been previously
      described.

PMID- 28740531
TI  - A case report: hypercalcemia due to vitamin supplementation in a patient with
      neurofibromatosis.
AB  - A 54-year-old female with history of neurofibromatosis who presented with severe
      hypercalcemia and renal failure secondary to over supplementation of calcium and
      vitamin D.

PMID- 28740532
TI  - Is this a seizure?
AB  - We describe a case of a 65-year-old woman admitted to the hospital for suspected
      of epileptic crisis. She was affected by diabetes and hiatal hernia for which she
      was taking Proton Pump Inhibitors (PPIs) for about 8 years. She showed
      hypocalcaemia, hypomagnesaemia, hyperparathyroidism and severe hypovitaminosis D.
      We exclude malabsorption and magnesium loss. After restored vitamin D levels,
      stopped use of PPI, start calcium and magnesium supplementation normal values of
      the ions were restored. This case underlies the importance of evaluate magnesium
      routinely, other than calcium and vitamin D, and use PPI more carefully.

PMID- 28740533
TI  - Histological and micro Computed Tomography analysis of a femoral stress fracture
      associated with prolonged bisphosphonate use.
AB  - BACKGROUND: The origin of atypical femoral fractures (AFF) associated with
      bisphosphonate therapy remains to be elucidated. In this study, a biopsy of an
      AFF site is analyzed to determine whether microdamage and/or morphological
      changes are present in the area of the AFF. MATERIAL AND METHODS: Cortical bone
      from an AFF region was obtained during a preventive stabilization in a patient
      with a symptomatic AFF. This bone was scanned using microCT (resolution=0.01 mm),
      stained with basic fuchsin and analyzed histologically. RESULTS: The diameter of
      the Haversian canals was higher in the vicinity of the AFF compared to the bone
      further away from the AFF. The bone mineral density within the cortex ranged from
      1020 to 1080 mg HA/cm3. We observed penetration of basic fuchsin into the matrix,
      which is a tell-tale sign of diffuse damage. DISCUSSION: The higher diameter of
      haversian canals is likely to result in higher local stresses and consequently
      increased microdamage. The diffuse microdamage in the biopsy may furthermore be
      directly related to bisphosphonate use, preventing repair of microdamage, and
      consequently the development of the AFF. CONCLUSION: Increased porosity of the
      cortex and accumulation of microdamage might have lead to a stress fracture and
      ultimately a complete AFF.

PMID- 28740534
TI  - Primary hyperparathyroidism associated to thrombocytopenia: an issue to consider?
AB  - Primary hyperparathyroidism (PHPT) is probably the most common endocrine disorder
      of the parathyroid glands, causing hypercalcemia. It is diagnosed often in
      persons with elevated serum calcium levels. However, hematological
      manifestations, such as thrombocytopenia are less known. In this case we describe
      the possible association of PHPT with reversible thrombocytopenia after
      parathyroidectomy. This hematological abnormality can be included in the spectrum
      of possible causes, including seemingly non-specific symptoms, in the decision
      tree towards surgical assessment.

PMID- 28740535
TI  - Acute severe diarrhoea and hyponatremia after zoledronic acid infusion: an acute
      phase reaction.
AB  - Zoledronic acid (ZA), an intravenous aminobisphosphonate, is prescribed widely
      for postmenopausal osteoporosis. It is a relatively safe drug but may cause
      adverse effects including acute phase reaction. Oral non-aminobisphosphonates are
      known to cause diarrhoea that is usually mild and self-limited. Intravenous amino
      bisphosphonates are not known to cause diarrhoea. We describe a case of acute
      watery diarrhoea complicated by severe hyponatremia and hypotension following ZA
      infusion. The patient needed intensive care for four days. To the best of our
      knowledge, this type of acute diarrhoea complicated by severe hyponatremia,
      following ZA infusion, is not reported so far. Strong temporal relation with ZA
      administration makes it the most likely cause. Furthermore, all laboratory and
      imaging parameters indicate that the secretory diarrhoea may be a component of
      acute phase reaction. According to World Health Organization (WHO) causality
      scale, ZA was a probable cause of acute watery diarrhoea in our patient.
      Clinicians should be aware that ZA administration can cause acute watery
      diarrhoea and may lead to severe hypotension and hyponatremia.

PMID- 28740536
TI  - LoCa LoPa myelopathy: is prevention better than cure?
AB  - Manifestations of primary hypoparathyroidism are produced by neuromuscular
      irritability or by extraosseous calcifications. We present a patient of primary
      hypoparathyroidism who had extensive calcification of brain parenchyma, and was
      suffering from chronic, generalised and progressive stiffness of body due to
      cervical compressive myelopathy, caused by calcification of posterior
      longitudinal ligament and ligamentum flavum. By presenting this case we wanted to
      emphasize the usefulness of meticulous clinical examination to differentiate the
      stiffness caused by myelopathy from that which is caused by possible coexisting
      extrapyramidal disorder. This case presentation also builds the hypothesis that
      early diagnosis and institution of early and appropriate treatment has potential
      to prevent the complications arising from extraosseous calcifications in patients
      with primary hypoparathyroidism.

PMID- 28740537
TI  - The Anti-Inflammatory Effects of Invigorating Kidney and Supplementing Qi Chinese
      Herbal Formulae in Asthma Patients.
AB  - BACKGROUND: The theories of Shen-reinforcement and Qi-supplementation are
      important in asthma treatment based on traditional Chinese medicine theories.
      Early studies suggested that Invigorating Kidney and Supplementing Qi herbal
      formulae, Bu Shen Fang Chuan (BSFC) and Bu Shen Yi Qi (BSYQ), conveyed promising
      results in asthma treatment. However, the efficacy and safety of the formulae
      need to be further investigated by a randomized double-blind clinical trial.
      METHODS: 328 eligible patients were randomly sent to BSFC, BSYQ, and placebo
      group. The two formulae were received as add-on therapy. The primary endpoints
      were rate of asthma exacerbation and Hamilton Rating Scale for Depression (HAM-D)
      score. The secondary endpoints included HPA axis function and inflammatory
      cytokine production profile. All indexes were measured before and after
      treatment. RESULTS: The primary endpoints were not improved in both groups;
      however, the depression levels of subgroup patients with HAM-D score > 5 were
      improved in BSFC group. HPA axis functions and inflammatory cytokines level were
      also improved by two formulae. The incidences of adverse events were similar
      among groups. CONCLUSIONS: The two formulae had multiple advantage effects on
      neuroendocrine-immune system. They are worth used as a replacement therapy in
      asthma. TRIAL REGISTRATION: This trial is registered with clinical trial number
      ChiCTR-PRC-09000529.

PMID- 28740538
TI  - Linarin Enriched Extract Attenuates Liver Injury and Inflammation Induced by High
      Fat High-Cholesterol Diet in Rats.
AB  - The aim of this study was to explore the potential beneficial effects of linarin
      enriched Flos Chrysanthemi extract (Lin-extract) on nonalcoholic steatohepatitis
      (NASH) induced by high-fat high-cholesterol (HFHC) diet in rats. SD rats received
      normal diet, HFHC diet, or HFHC diet plus different doses of Lin-extract. The
      liver content of triglyceride and total cholesterol markedly increased in HFHC
      diet-fed model rats while middle and high dose of Lin-extract lowered liver
      cholesterol significantly. The expression of stearoyl-CoA desaturase (SCD1) was
      upregulated by HFHC diet and further elevated by high dose Lin-extract. High dose
      of Lin-extract also markedly lowered the serum alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) and inhibited the activation of c-Jun N-terminal
      kinase (JNK) induced by HFHC in livers. The HFHC-increased mRNA levels of hepatic
      inflammation cytokines, including monocyte chemotactic protein-1 (MCP-1), tumor
      necrosis factor-alpha (TNF-alpha), and chemokine (C-X-C motif) ligand 1 (CXCL1),
      were suppressed by Lin-extract dose-dependently. Furthermore, pathology
      evaluation showed that high dose Lin-extract greatly improved lobular
      inflammation. Our results suggest that Lin-extract could attenuate liver injury
      and inflammation induced by HFHC diet in rats. Its modulatory effect on lipid
      metabolism may partially contribute to this protective effect.

PMID- 28740539
TI  - Identifying Chinese Herbal Medicine Network for Endometriosis: Implications from
      a Population-Based Database in Taiwan.
AB  - BACKGROUND: Endometriosis is a common but bothersome gynecological disease, and
      Chinese herbal medicine (CHM) is used for treating endometriosis. The aim of this
      study is to explore CHM network and core treatments for endometriosis by
      analyzing nationwide CHM prescription database. METHODS: From 1998 to 2013, the
      CHM prescriptions made primarily for endometriosis among women diagnosed with
      endometriosis (ICD-9-CM code: 671) by gynecologists during their reproductive age
      were collected. CHM network analysis was then carried out by using association
      rule mining and social network analysis. RESULTS: A total of 12,986 CHM
      prescriptions made for endometriosis were analyzed. There were 556 kinds of CHM
      ever used, and, in average, each prescription was composed of 6.2 CHMs. Gui-Zhi
      Fu-Ling-Wan (GZFLW) was used most frequently, followed by Cyperus rotundus (28.1%
      and 18.8% of all prescriptions, resp.). Additionally, the combination of Cyperus
      rotundus with GZFLW (8.0%) was the most frequently used combination of two CHMs.
      CHM network showed that GZFLW was the core CHM for endometriosis and graphically
      demonstrated the extensive coverage of TCM syndromes and pathogenesis of
      endometriosis. CONCLUSIONS: CHM network provides graphical demonstration and
      summary of commonly used CHMs for endometriosis, and further studies are
      warranted based on these findings.

PMID- 28740540
TI  - Phytochemistry and Pharmacological Studies of Citrus macroptera: A Medicinal
      Plant Review.
AB  - Citrus macroptera (family Rutaceae), commonly known as Sat Kara, is a
      pharmacologically diverse medicinal plant. Various parts of this plant,
      specifically fruit, have an immense range of medicinal uses in folk medicine
      directed for a number of ailments. A plethora of active phytochemical
      constituents of this plant have been revealed so far, namely, limonene, beta
      caryophyllene, beta-pinene, geranial edulinine, ribalinine, isoplatydesmine, and
      so forth. Several studies demonstrated the exploration of pharmacological
      potential of various parts such as fruits, leaves, and stems of C. macroptera as
      antioxidant, cytotoxic, antimicrobial, thrombolytic, hypoglycemic, anxiolytic,
      antidepressant, cardioprotective, and hepatoprotective. Furthermore, inhibition
      of in vitro alpha-amylase, inhibition of paracetamol induced hepatotoxicity, and
      potentiation of brain antioxidant enzyme are also ascertained. In present review,
      comprehensive study focused on knowledge regarding several phytopharmacological
      activities of Citrus macroptera has been described.

PMID- 28740541
TI  - A Selective Ensemble Classification Method Combining Mammography Images with
      Ultrasound Images for Breast Cancer Diagnosis.
AB  - Breast cancer has been one of the main diseases that threatens women's life.
      Early detection and diagnosis of breast cancer play an important role in reducing
      mortality of breast cancer. In this paper, we propose a selective ensemble method
      integrated with the KNN, SVM, and Naive Bayes to diagnose the breast cancer
      combining ultrasound images with mammography images. Our experimental results
      have shown that the selective classification method with an accuracy of 88.73%
      and sensitivity of 97.06% is efficient for breast cancer diagnosis. And indicator
      R presents a new way to choose the base classifier for ensemble learning.

PMID- 28740542
TI  - Vandetanib-eluting Radiopaque Beads: In vivo Pharmacokinetics, Safety and
      Toxicity Evaluation following Swine Liver Embolization.
AB  - PURPOSE: To evaluate the plasma and tissue pharmacokinetics, safety and toxicity
      following intra-arterial hepatic artery administration of Vandetanib (VTB)
      eluting Radiopaque Beads (VERB) in healthy swine. MATERIALS AND METHODS: In a
      first phase, healthy swine were treated with hepatic intra-arterial
      administration of VERB at target dose loading strengths of 36 mg/mL (VERB36), 72
      mg/mL (VERB72) and 120 mg/mL (VERB120). Blood and tissue samples were taken and
      analysed for VTB and metabolites to determine pharmacokinetic parameters for the
      different dose forms over 30 days. In a second phase, animals were treated with
      unloaded radiopaque beads or high dose VTB loaded beads (VERB100, 100 mg/mL).
      Tissue samples from embolized and non-embolized areas of the liver were evaluated
      at necropsy (30 and 90 days) for determination of VTB and metabolite levels and
      tissue pathology. Imaging was performed prior to sacrifice using multi-detector
      computed tomography (MDCT) and imaging findings correlated with pathological
      changes in the tissue and location of the radiopaque beads. RESULTS: The peak
      plasma levels of VTB (Cmax) released from the various doses of VERB ranged
      between 6.19-17.3 ng/mL indicating a low systemic burst release. The plasma
      profile of VTB was consistent with a distribution phase up to 6 h after
      administration followed by elimination with a half-life of 20-23 h. The AUC of
      VTB and its major metabolite N-desmethyl vandetanib (NDM VTB) was approximately
      linear with the dose strength of VERB. VTB plasma levels were at or below limits
      of detection two weeks after administration. In liver samples, VTB and NDM VTB
      were present in treated sections at 30 days after administration at levels above
      the in vitro IC50 for biological effectiveness. At 90 days both analytes were
      still present in treated liver but were near or below the limit of quantification
      in untreated liver sections, demonstrating sustained release from the VERB.
      Comparison of the reduction of the liver lobe size and associated tissue changes
      suggested a more effective embolization with VERB compared to the beads without
      drug. CONCLUSIONS: Hepatic intra-arterial administration of VERB results in a low
      systemic exposure and enables sustained delivery of VTB to target tissues
      following embolization. Changes in the liver tissue are consistent with an
      effective embolization and this study has demonstrated that VERB100 is well
      tolerated with no obvious systemic toxicity.

PMID- 28740543
TI  - Self-Assembly of Semiconducting-Plasmonic Gold Nanoparticles with Enhanced
      Optical Property for Photoacoustic Imaging and Photothermal Therapy.
AB  - Although various noble metal and semiconducting molecules have been developed as
      photoacoustic (PA) agents, the use of semiconducting polymer-metal nanoparticle
      hybrid materials to enhance PA signal has not been explored. A novel
      semiconducting-plasmonic nanovesicle was fabricated by self-assembly of
      semiconducting poly(perylene diimide) (PPDI) and poly(ethylene glycol (PEG)
      tethered gold nanoparticles (Au@PPDI/PEG). A highly localized and strongly
      enhanced electromagnetic (EM) field is distributed between adjacent gold
      nanoparticles in the vesicular shell, where the absorbing collapsed PPDI is
      present. Significantly, the EM field in turn enhances the light absorption
      efficiency of PPDI, leading to a much greater photothermal effect and a stronger
      photoacoustic signal compared to PDI nanoparticle or gold nanovesicle alone. The
      optical property of the hybrid vesicle can be further tailored by controlling the
      ratio of PPDI and gold nanoparticle as well as the adjustable interparticle
      distance of gold nanoparticles localized in the vesicular shell. In vivo imaging
      and therapeutic evaluation demonstrated that the hybrid vesicle is an excellent
      probe for cancer theranostics.

PMID- 28740544
TI  - Interleukin-32alpha Inhibits Endothelial Inflammation, Vascular Smooth Muscle
      Cell Activation, and Atherosclerosis by Upregulating Timp3 and Reck through
      suppressing microRNA-205 Biogenesis.
AB  - Interleukin-32 (IL-32) is a multifaceted cytokine that promotes inflammation and
      regulates vascular endothelial cell behavior. Although some IL-32 isoforms have
      been reported to contribute to vascular inflammation and atherosclerosis, the
      functional role of IL-32alpha in vascular inflammation and atherogenesis has not
      been studied. Methods: IL-32alpha function was assessed in cells with transient
      IL-32alpha overexpression or treated with recombinant human IL-32alpha by western
      blotting and mRNA expression analysis. Vascular smooth muscle cell (VSMC)
      proliferation and migration was examined by BrdU incorporation and wound healing
      assays, respectively. In addition, the participation of IL-32alpha on vascular
      inflammation, arterial wall thickening, and atherosclerosis in vivo was monitored
      in human IL-32alpha transgenic (hIL-32alpha-Tg) mice with or without ApoE
      knockout (ApoE -/- /hIL-32alpha-Tg). Results: Our analyses showed that IL-32alpha
      suppresses genes involved in the inflammatory and immune responses and cell
      proliferation, and by limiting matrix metalloproteinase (MMP) function. In vivo,
      administration of hIL-32alpha inhibited vascular inflammation and atherosclerosis
      in hIL-32alpha-Tg and ApoE -/- /hIL-32alpha-Tg mice. Subsequent microarray and in
      silico analysis also revealed a marked decreased in inflammatory gene expression
      in hIL-32alpha-Tg mice. Collectively, our studies demonstrated that IL-32alpha
      upregulates the atheroprotective genes Timp3 and Reck by downregulating microRNA
      205 through regulation of the Rprd2-Dgcr8/Ddx5-Dicer1 biogenesis pathway.
      Conclusion: Our findings provide the first direct evidence that IL-32alpha is an
      anti-inflammatory and anti-atherogenic cytokine that may be useful as a
      diagnostic and therapeutic protein in atherosclerosis.

PMID- 28740545
TI  - E-selectin-targeted Sialic Acid-PEG-dexamethasone Micelles for Enhanced Anti
      Inflammatory Efficacy for Acute Kidney Injury.
AB  - The effective treatment for acute kidney injury (AKI) is currently limited, and
      care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewisx
      antigen on the mammalian cell surface, which participates in E-selectin binding.
      Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid
      polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are
      designed for ameliorating AKI. The conjugates are synthesized via the
      esterification reaction between PEG and SA or DXM, and can spontaneously form
      micelles in an aqueous solution with a 65.6 ug/mL critical micelle concentration.
      Free DXM is incorporated into the micelles with 6.28 +/- 0.21% drug loading
      content. In vitro DXM release from SA-PEG-DXM/DXM micelles can be prolonged to
      48h. Much more SA-PEG-DXM micelles can be internalized by lipopolysaccharide
      (LPS)-activated human umbilical vein endothelial cells (HUVECs) in comparison to
      PEG-DXM micelles due to specific interaction between SA and E-selectin expressed
      on HUVECs, and consequently more SA-PEG-DXM micelles are accumulated in the
      kidney of AKI murine model. Furthermore, SA in SA-PEG-DXM conjugates can
      significantly ameliorate LPS-induced production of pro-inflammatory cytokines via
      suppressing LPS-activated Beclin-1/Atg5-Atg12-mediated autophagy to attenuate
      toxicity. Compared with free DXM and PEG-DXM/DXM micelles, SA-PEG-DXM/DXM
      micelles show better therapeutical effects, as reflected by the improved renal
      function, histopathological changes, pro-inflammatory cytokines, oxidative stress
      and expression of apoptotic related proteins.

PMID- 28740546
TI  - A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with
      Real-Time Simultaneous Detection of Multiple DNA Targets.
AB  - Paper-based diagnostic devices have many advantages as a one of the multiple
      diagnostic test platforms for point-of-care (POC) testing because they have
      simplicity, portability, and cost-effectiveness. However, despite high
      sensitivity and specificity of nucleic acid testing (NAT), the development of NAT
      based on a paper platform has not progressed as much as the others because
      various specific conditions for nucleic acid amplification reactions such as pH,
      buffer components, and temperature, inhibitions from technical differences of
      paper-based device. Here, we propose a paper-based device for performing loop
      mediated isothermal amplification (LAMP) with real-time simultaneous detection of
      multiple DNA targets. We determined the optimal chemical components to enable dry
      conditions for the LAMP reaction without lyophilization or other techniques. We
      also devised the simple paper device structure by sequentially stacking
      functional layers, and employed a newly discovered property of hydroxynaphthol
      blue fluorescence to analyze real-time LAMP signals in the paper device. This
      proposed platform allowed analysis of three different meningitis DNA samples in a
      single device with single-step operation. This LAMP-based multiple diagnostic
      device has potential for real-time analysis with quantitative detection of 102
      105 copies of genomic DNA. Furthermore, we propose the transformation of DNA
      amplification devices to a simple and affordable paper system approach with great
      potential for realizing a paper-based NAT system for POC testing.

PMID- 28740547
TI  - Down-regulated miR-23a Contributes to the Metastasis of Cutaneous Melanoma by
      Promoting Autophagy.
AB  - Melanoma is among the most aggressive tumors, and the occurrence of metastasis
      leads to a precipitous drop in the patients' survival. Therefore, identification
      of metastasis-associated biomarkers and therapeutic targets will contribute a lot
      to improving melanoma theranostics. Recently, microRNAs (miRNAs) have been
      implicated in modulating cancer invasion and metastasis, and are proved as
      potential non-invasive biomarkers in sera for various tumors. Here, we reported
      miR-23a as a novel metastasis-associated miRNA that played a remarkable role in
      modulating melanoma invasive and metastatic capacity and was of great value in
      predicting melanoma metastasis and prognosis. We found that serum miR-23a level
      was significantly down-regulated in metastatic melanoma patients and highly
      correlated with poor clinical outcomes. In addition, miR-23a level was also
      remarkably decreased in metastatic melanoma tissues and cell lines. Furthermore,
      overexpressed miR-23a suppressed the invasive and migratory property of melanoma
      cells by abrogating autophagy through directly targeting ATG12. Specially, miR
      23a-ATG12 axis attenuated melanoma invasion and migration through autophagy
      mediated AMPK-RhoA pathway. Finally, the overexpression of miR-23a prevented
      melanoma metastasis in vivo. Taken together, our findings demonstrate that the
      metastasis-associated miR-23a is not only a potential biomarker, but also a
      valuable therapeutic target for melanoma.

PMID- 28740548
TI  - Modulation of Salmonella Tumor-Colonization and Intratumoral Anti-angiogenesis by
      Triptolide and Its Mechanism.
AB  - The weakened tumour colonization of attenuated Salmonella has severely hampered
      its clinical development. In this study, we investigated whether an anti
      inflammation and antiangiogenesis compound triptolide could improve the efficacy
      of VNP20009, a highly attenuated Salmonella strain, against mice melanoma. By
      comparing the effects of conventional VNP20009 monotherapy and a combination
      therapy that uses both triptolide and VNP20009, we found that triptolide
      significantly improved the tumour colonization of VNP20009 by reducing the number
      of infiltrated neutrophils in the melanoma, which led to a larger necrotic area
      in the melanoma. Moreover, the combination therapy suppressed tumour angiogenesis
      by reducing the expression of VEGF in a synergistic manner, retarding the growth
      of the melanoma. Our study revealed that triptolide could significantly enhance
      the antitumour effect of VNP20009 by modulating tumour angiogenesis and the host
      immune response, providing a new understanding of the strategy to improve
      Salmonella-mediated tumour therapy.

PMID- 28740549
TI  - Targeted Delivery to Tumor-associated Pericytes via an Affibody with High
      Affinity for PDGFRbeta Enhances the in vivo Antitumor Effects of Human TRAIL.
AB  - Human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) has
      exhibited superior in vitro cytotoxicity in a variety of tumor cells. However,
      hTRAIL showed a disappointing anticancer effect in clinical trials, although
      hTRAIL-based regimens were well tolerated. One important reason might be that
      hTRAIL was largely trapped by its decoy receptors, which are ubiquitously
      expressed on normal cells. Tumor-targeted delivery might improve the tumor uptake
      and thus enhance the antitumor effect of hTRAIL. Platelet-derived growth factor
      receptor beta (PDGFRbeta)-expressing pericytes are enriched in tumor tissues
      derived both from patients with colon cancer and from mice bearing colorectal
      tumor xenografts. A ZPDGFRbeta affibody showed high affinity (nM) for PDGFRbeta
      and was predominantly distributed on tumor-associated PDGFRbeta-positive
      pericytes. Co-administration with the ZPDGFRbeta affibody did not significantly
      enhance the antitumor effect of hTRAIL in mice bearing tumor xenografts. Fusion
      to the ZPDGFRbeta affibody endows hTRAIL with PDGFRbeta-binding ability but does
      not interfere with its death receptor binding and activation. The fused
      ZPDGFRbeta affibody mediated PDGFRbeta-dependent binding of hTRAIL to pericytes.
      In addition, hTRAIL bound on pericytes could kill tumor cells through juxtatropic
      activity or exhibit cytotoxicity in tumor cells after being released from
      pericytes. Intravenously injected hTRAIL fused to ZPDGFRbeta affibody initially
      accumulated on tumor-associated pericytes and then diffused to the tumor
      parenchyma over time. Fusion to the ZPDGFRbeta affibody increased the tumor
      uptake of hTRAIL, thus enhancing the antitumor effect of hTRAIL in mice bearing
      tumor xenografts. These results demonstrate that pericyte-targeted delivery
      mediated by a ZPDGFRbeta affibody is an alternative strategy for tumor-targeted
      delivery of anticancer agents.

PMID- 28740550
TI  - Boosting the Peroxidase-Like Activity of Nanostructured Nickel by Inducing Its 3+
      Oxidation State in LaNiO3 Perovskite and Its Application for Biomedical Assays.
AB  - Catalytic nanomaterials with intrinsic enzyme-like activities, called nanozymes,
      have recently attracted significant research interest due to their unique
      advantages relative to natural enzymes and conventional artificial enzymes. Among
      the nanozymes developed, particular interests have been devoted to nanozymes with
      peroxidase mimicking activities because of their promising applications in
      biosensing, bioimaging, biomedicine, etc. Till now, lots of functional
      nanomaterials have been used to mimic peroxidase. However, few studies have
      focused on the Ni-based nanomaterials for peroxidase mimics. In this work, we
      obtained the porous LaNiO3 nanocubes with high peroxidase-like activity by
      inducing its 3+ oxidation state in LaNiO3 perovskite and optimizing the
      morphology of LaNiO3 perovskite. The peroxidase mimicking activity of the porous
      LaNiO3 nanocubes with Ni3+ was about 58~fold and 22~fold higher than that of NiO
      with Ni2+ and Ni nanoparticles with Ni0. More, the porous LaNiO3 nanocubes
      exhibited about 2-fold higher activity when compared with LaNiO3 nanoparticles.
      Based on the superior peroxidase-like activity of porous LaNiO3 nanocubes, facile
      colorimetric assays for H2O2, glucose, and sarcosine detection were developed.
      Our present work not only demonstrates a useful strategy for modulating
      nanozymes' activities but also provides promising bioassays for clinical
      diagnostics.

PMID- 28740551
TI  - Modulating microRNAs as Novel Therapeutic Targets in Cardiac Fibrosis.
AB  - This commentary highlights the findings by Tao et al. (Theranostics 2016; 6: 2068
      2083) that targeting miR-433 may be a potential therapeutic strategy for
      myocardial fibrosis and subsequently discusses the obstacles and prospects
      associated with the application of therapeutic microRNAs in anti-fibrosis
      treatment.

PMID- 28740552
TI  - NPM1 Mutant Mediated PML Delocalization and Stabilization Enhances Autophagy and
      Cell Survival in Leukemic Cells.
AB  - Accumulating evidence has defined nucleophosmin 1 (NPM1) mutation as a driver
      genetic event in acute myeloid leukemia (AML), whereas the pathogenesis of NPM1
      mutated AML remains to be fully elucidated. In this study, we showed that mutant
      NPM1 elevated autophagic activity and autophagic activation contributed to
      leukemic cell survival in vitro. Meanwhile, we also found high expression of
      promyelocytic leukemia gene (PML) and its cytoplasmic dislocation in primary NPM1
      mutated AML blasts and NPM1-mA positive OCI-AML3 cells. Mechanically, mutant NPM1
      interacted with PML and mediated it delocalization as well as stabilization.
      Notably, NPM1-mA knockdown impaired autophagic activity, while induced expression
      of PML reversed this effect. Finally, we confirmed that PML modulated autophagic
      activity via AKT signal. These findings suggest that aberrant PML expression and
      autophagy are beneficial to the leukemic transformation driven by NPM1 mutations.
      This indicates an attractive therapeutic avenue for PML targeting and/or
      autophagy inhibition in the treatment of NPM1-mutated AML.

PMID- 28740553
TI  - A Fluorogenic Probe for Ultrafast and Reversible Detection of Formaldehyde in
      Neurovascular Tissues.
AB  - Formaldehyde (FA) is endogenously produced in live systems and has been
      implicated in a diverse array of pathophysiological processes. To disentangle the
      detailed molecular mechanisms of FA biology, a reliable method for monitoring FA
      changes in live cells would be indispensable. Although there have been several
      fluorescent probes reported to detect FA, most are limited by the slow detection
      kinetics and the intrinsic disadvantage of detecting FA in an irreversible manner
      which may disturb endogenous FA homeostasis. Herein we developed a coumarin
      hydrazonate based fluorogenic probe (PFM) based on a finely-tailored
      stereoelectronic effect. PFM could respond to FA swiftly and reversibly. This,
      together with its desirable specificity and sensitivity, endows us to track
      endogenous FA in live neurovascular cells with excellent temporal and spatial
      resolution. Further study in the brain tissue imaging showed the first direct
      observation of aberrant FA accumulation in cortex and hippocampus of Alzheimer's
      mouse model, indicating the potential of PFM as a diagnostic tool.

PMID- 28740554
TI  - Concurrent Chemoradiotherapy with or without Anti-EGFR-Targeted Treatment for
      Stage II-IVb Nasopharyngeal Carcinoma: Retrospective Analysis with a Large Cohort
      and Long Follow-up.
AB  - We examined the benefits of the combination of anti-EGFR targeted treatment,
      cetuximab (CTX) or nimotuzumab (NTZ) and concurrent platinum-based
      chemoradiotherapy (CCRT) compared with CCRT alone in patients with stage II - IVb
      nasopharyngeal carcinoma (NPC). A total of 1,628 eligible patients with stage II 
      IVb NPC, who received CCRT (three cycles of 100 mg/m2 cisplatin every 3 weeks
      with intensity-modulated radiotherapy) with or without CTX or NTZ between June
      2009 and December 2013 were included in the analysis. Using propensity scores to
      adjust for potential prognostic factors, a well-balanced cohort of 878 patients
      was created by matching each patient who received CTX or NTZ plus CCRT with no
      more than four patients who received CCRT alone (1:4). Efficacy and safety were
      compared between CTX/NTZ plus CCRT and CCRT alone arms. Compared with CCRT alone,
      treatment with CTX/NTZ plus CCRT was associated with a significantly increased
      overall survival (3-year OS, 96.6% vs. 92.9%, P = 0.015), improved disease-free
      survival (3-year DFS, 93.5% vs 86.9%, P = 0.028), and improved distant metastasis
      free survival (3-year DMFS, 94.6% vs 89.3%, P = 0.030). Increased rate of CTX
      related-skin reaction and mucositis was observed in the CTX plus CCRT arm.
      Multivariate analysis demonstrated the combination of CTX/NTZ was a significant
      protective factor for OS, DFS, and DMFS in patients treated with CCRT. Our
      analysis suggests that the addition of CTX/NTZ to CCRT is more effective for
      maximizing survival in patients with stage II-IVb NPC compared with CCRT alone.

PMID- 28740555
TI  - Atg9b Deficiency Suppresses Autophagy and Potentiates Endoplasmic Reticulum
      Stress-Associated Hepatocyte Apoptosis in Hepatocarcinogenesis.
AB  - The aim of this study was to investigate the mechanism underlying autophagy
      deficiency during hepatic carcinogenesis. For this purpose, we used choline
      deficient, amino acid-defined (CDAA) hepatocarcinogenesis model in mice. miRNA
      microarrays combined with computational target predictions and GO analysis were
      used to identify molecular processes involved in carcinogenesis. PCR profiler
      array was employed to detect the dysregulated autophagy-related genes during
      carcinogenesis. We observed induction of hepatic tumours with increased
      inflammation, DNA damage, and cell death. These cellular processes were
      particularly detected upon oncogenic transformation of hepatocytes in which ER
      stress was excessively induced. Microarray combined with GO analysis showed that
      transformation of hepatocytes resulted in dysregulated events associated with
      cytoplasmic vesicle formation, which, in turn, was related to ER stress-induced
      autophagy. Defects of autophagy were observed in livers harbouring tumours and
      suffered a loss of expression of autophagy-related protein 9b (Atg9b).
      Hepatocytes lacking Atg9b were vulnerable to cell death induced by ER stress
      stimulus mainly caused by accumulation of ubiquitinated proteins. Loss of Atg9b
      also blocked recruitment of p62-associated ubiquitinated protein for
      autophagosome-lysosome degradation as Atg9b-driven phagophores may facilitate
      docking of both LC3 and p62 to initiate autophagy-associated degradation. miR
      3091-3p from tumour-derived exosomes, which were internalised by hepatocytes,
      could suppress Atg9b expression. Observations from this study advance our
      knowledge about the regulation of autophagy during hepatocarcinogenesis.

PMID- 28740557
TI  - Application of phase-change materials in memory taxonomy.
AB  - Phase-change materials are suitable for data storage because they exhibit
      reversible transitions between crystalline and amorphous states that have
      distinguishable electrical and optical properties. Consequently, these materials
      find applications in diverse memory devices ranging from conventional optical
      discs to emerging nanophotonic devices. Current research efforts are mostly
      devoted to phase-change random access memory, whereas the applications of phase
      change materials in other types of memory devices are rarely reported. Here we
      review the physical principles of phase-change materials and devices aiming to
      help researchers understand the concept of phase-change memory. We classify phase
      change memory devices into phase-change optical disc, phase-change scanning probe
      memory, phase-change random access memory, and phase-change nanophotonic device,
      according to their locations in memory hierarchy. For each device type we discuss
      the physical principles in conjunction with merits and weakness for data storage
      applications. We also outline state-of-the-art technologies and future prospects.

PMID- 28740556
TI  - YD277 Suppresses Triple-Negative Breast Cancer Partially Through Activating the
      Endoplasmic Reticulum Stress Pathway.
AB  - Triple-negative breast cancer (TNBC) is an aggressive malignancy with poor
      clinical outcomes. YD277 is a novel small molecule derived from ML264, a KLF5
      inhibitor that elicits cytotoxic effects in colon cancer cell lines. Our previous
      studies suggest that Krupple-like factor 5 (KLF5) is a promising therapeutic
      target for TNBC. In this study, we demonstrated that YD277 significantly induced
      G1 cell cycle arrest and apoptosis in MDA-MB-231 and MDA-MB-468 TNBC cells,
      independent of KLF5 inhibition. YD277 also reduced the protein expression levels
      of Cyclin D1, Bcl2 and Bclxl and promoted the expression of p21 and p27.
      Moreover, the pro-apoptotic activity of YD277 in TNBC was mediated by the
      transcription of IRE1alpha, a key molecule in the endoplasmic reticulum (ER)
      stress pathway. Finally, YD277 (15 mg/kg) significantly suppressed the growth of
      MDA-MB-231 tumor xenografts in nude mice. These findings indicate that YD277 is a
      promising chemotherapeutic candidate for TNBC.

PMID- 28740558
TI  - Thermoelectric La-doped SrTiO3 epitaxial layers with single-crystal quality: from
      nano to micrometers.
AB  - High-quality thermoelectric La0.2Sr0.8TiO3 (LSTO) films, with thicknesses ranging
      from 20 nm to 0.7 MUm, have been epitaxially grown on SrTiO3(001) substrates by
      enhanced solid-source oxide molecular-beam epitaxy. All films are atomically flat
      (with rms roughness < 0.2 nm), with low mosaicity (<0.1 degrees ), and present
      very low electrical resistivity (<5 * 10-4 Omega cm at room temperature), one
      order of magnitude lower than standard commercial Nb-doped SrTiO3 single
      crystalline substrate. The conservation of transport properties within this
      thickness range has been confirmed by thermoelectric measurements where Seebeck
      coefficients of approximately -60 MUV/K have been recorded for all films. These
      LSTO films can be integrated on Si for non-volatile memory structures or opto
      microelectronic devices, functioning as transparent conductors or thermoelectric
      elements.

PMID- 28740559
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1080/14686996.2016.1240575.].

PMID- 28740560
TI  - Flexible cellulose and ZnO hybrid nanocomposite and its UV sensing
      characteristics.
AB  - This paper reports the synthesis and UV sensing characteristics of a cellulose
      and ZnO hybrid nanocomposite (CEZOHN) prepared by exploiting the synergetic
      effects of ZnO functionality and the renewability of cellulose. Vertically
      aligned ZnO nanorods were grown well on a flexible cellulose film by direct ZnO
      seeding and hydrothermal growing processes. The ZnO nanorods have the wurtzite
      structure and an aspect ratio of 9 ~ 11. Photoresponse of the prepared CEZOHN was
      evaluated by measuring photocurrent under UV illumination. CEZOHN shows bi
      directional, linear and fast photoresponse as a function of UV intensity.
      Electrode materials, light sources, repeatability, durability and flexibility of
      the prepared CEZOHN were tested and the photocurrent generation mechanism is
      discussed. The silver nanowire coating used for electrodes on CEZOHN is
      compatible with a transparent UV sensor. The prepared CEZOHN is flexible,
      transparent and biocompatible, and hence can be used for flexible and wearable UV
      sensors.

PMID- 28740561
TI  - EDTA-assisted phase conversion synthesis of (Gd0.95RE0.05)PO4 nanowires (RE = Eu,
      Tb) and investigation of photoluminescence.
AB  - Hexagonal (Gd0.95RE0.05)PO4.nH2O nanowires ~300 nm in length and ~10 nm in
      diameter have been converted from (Gd0.95RE0.05)2(OH)5NO3.nH2O nanosheets (RE =
      Eu, Tb) in the presence of monoammonium phosphate (NH4H2PO4) and ethylene diamine
      tetraacetic acid (EDTA). They were characterized by X-ray diffraction,
      thermogravimetry, electron microscopy, and Fourier transform infrared and
      photoluminescence spectroscopies. It is shown that EDTA played an essential role
      in the morphology development of the nanowires. The hydrothermal products
      obtained up to 180  degrees C are of a pure hexagonal phase, while monoclinic
      phosphate evolved as an impurity at 200  degrees C. The nanowires undergo
      hexagonal->monoclinic phase transformation upon calcination at >=600  degrees C
      to yield a pure monoclinic phase at ~900  degrees C. The effects of calcination
      on morphology, excitation/emission, and fluorescence decay kinetics were
      investigated in detail with (Gd0.95Eu0.05)PO4 as example. The abnormally strong
      5D0->7F4 electric dipole Eu3+ emission in the hexagonal phosphates was ascribed
      to site distortion. The process of energy migration was also discussed for the
      optically active Gd3+ and Eu3+/Tb3+ ions.

PMID- 28740562
TI  - Mo6 cluster-based compounds for energy conversion applications: comparative study
      of photoluminescence and cathodoluminescence.
AB  - We report the photoluminescence (PL) and cathodoluminescence (CL) properties of
      face-capped [Mo6Xi8La6]2- (X = Cl, Br, I; L = organic or inorganic ligands)
      cluster units. We show that the emission of Mo6 metal atom clusters depends not
      only on the nature of X and L ligands bound to the cluster and counter-cations,
      but also on the excitation source. Seven members of the AxMo6Xi8La6 series (A =
      Cs+, (n-C4H9)4N+, NH4+) were selected to evaluate the influence of counter
      cations and ligands on de-excitation mechanisms responsible for multicomponent
      emission of cluster units. This study evaluates the ageing of each member of the
      series, which is crucial for further energy conversion applications
      (photovoltaic, lighting, water splitting, etc.).

PMID- 28740563
TI  - The impact of Ti and temperature on the stability of Nb5Si3 phases: a first
      principles study.
AB  - Nb-silicide based alloys could be used at T > 1423 K in future aero-engines.
      Titanium is an important additive to these new alloys where it improves
      oxidation, fracture toughness and reduces density. The microstructures of the new
      alloys consist of an Nb solid solution, and silicides and other intermetallics
      can be present. Three Nb5Si3 polymorphs are known, namely alphaNb5Si3 (tI32 Cr5B3
      type, D8l), betaNb5Si3 (tI32 W5Si3-type, D8m) and gammaNb5Si3 (hP16 Mn5Si3-type,
      D88). In these 5-3 silicides Nb atoms can be substituted by Ti atoms. The type of
      stable Nb5Si3 depends on temperature and concentration of Ti addition and is
      important for the stability and properties of the alloys. The effect of
      increasing concentration of Ti on the transition temperature between the
      polymorphs has not been studied. In this work first-principles calculations were
      used to predict the stability and physical properties of the various Nb5Si3
      silicides alloyed with Ti. Temperature-dependent enthalpies of formation were
      computed, and the transition temperature between the low (alpha) and high (beta)
      temperature polymorphs of Nb5Si3 was found to decrease significantly with
      increasing Ti content. The gammaNb5Si3 was found to be stable only at high Ti
      concentrations, above approximately 50 at. % Ti. Calculation of physical
      properties and the Cauchy pressures, Pugh's index of ductility and Poisson ratio
      showed that as the Ti content increased, the bulk moduli of all silicides
      decreased, while the shear and elastic moduli and the Debye temperature increased
      for the alphaNb5Si3 and gammaNb5Si3 and decreased for betaNb5Si3. With the
      addition of Ti the alphaNb5Si3 and gammaNb5Si3 became less ductile, whereas the
      betaNb5Si3 became more ductile. When Ti was added in the alphaNb5Si3 and
      betaNb5Si3 the linear thermal expansion coefficients of the silicides decreased,
      but the anisotropy of coefficient of thermal expansion did not change
      significantly.

PMID- 28740564
TI  - Can Diffusion Weighted Imaging Aid in Differentiating Benign from Malignant
      Sinonasal Masses?: A Useful Adjunct.
AB  - BACKGROUND: To evaluate the role of diffusion weighted imaging (DWI) and apparent
      diffusion coefficient (ADC) values at 3 Tesla in characterizing sinonasal masses.
      MATERIAL/METHODS: After ethical clearance, 79 treatment naive patients with head
      and neck masses underwent magnetic resonance imaging (MRI), including DWI at 3
      Tesla using the following b values - 0, 500 and 1000 s/mm2. Thirty-one patients
      were found to have sinonasal tumours and were subsequently analysed. Image
      analysis consisted of a morphological evaluation of conventional MR images,
      qualitative evaluation of DW trace images and quantitative assessment of mean ADC
      values. Receiver operating characteristic (ROC) curve was drawn to determine a
      cut-off ADC value for the differentiation between benign and malignant masses.
      RESULTS: Sinonasal masses showed an overlapping growth pattern on conventional
      imaging, irrespective of their biological nature. The mean ADC value of benign
      lesions was 1.948+/-0.459*10-3 mm2/s, while that of malignant lesions was 1.046+/
      0.711*10-3 mm2/s, and the difference was statistically significant (p=0.004).
      When a cut-off ADC value of 1.791*10-3 mm2/s was used, sensitivity of 80% and
      specificity of 83.3% were obtained for characterization of malignant lesions,
      which was statistically significant. Juvenile nasopharyngeal angiofibroma (JNA)
      showed distinctly high ADC values, while meningioma was the only benign lesion
      with restricted diffusion. Atypical entities with unexpected diffusion
      characteristics included: adenocarcinoma, adenoid cystic carcinoma, meningioma,
      chondrosarcoma and fibromyxoid sarcoma. CONCLUSIONS: DWI in conjunction with
      conventional imaging can potentially enhance the diagnostic accuracy in
      characterizing sinonasal masses as benign or malignant. Some specific entities
      such as JNA and meningioma showed distinctive diffusion characteristics.

PMID- 28740565
TI  - Whole-Body Low-Dose Computed Tomography (WBLDCT) in Assessment of Patients with
      Multiple Myeloma - Pilot Study and Standard Imaging Protocol Suggestion.
AB  - BACKGROUND: For decades, the main imaging tool in multiple myeloma (MM) patients
      was plain radiography. However, computed tomography (CT) has been included in the
      updated criteria of MM. The main disadvantage of CT is a considerably high
      radiation dose. Therefore, low-dose CT protocols could be a solution. The aim of
      the study was to (1) preliminarily analyse the usefulness of Whole-Body Low-Dose
      CT (WBLDCT) in the evaluation of patients with MM and (2) to make adjustments in
      the standard CT imaging protocol. MATERIAL/METHODS: In 41 patients with MM,
      WBLDCT was performed. The following parameters were used: detector configuration 
      80*0.5 mm, scanning range in a single spiral acquisition from the skull to the
      proximal femoral bones, tube voltage - 120 kVp, current tube time product - 86
      mAs, slice thickness 1 mm. Two sets of axial images were reconstructed for bone
      and soft tissue assessment, respectively. Secondary coronal and sagittal
      reconstructions were generated. Typical MM features were analysed and
      qualitatively compared with radiography results. RESULTS: A potentially increased
      sensitivity of CT, as compared to radiography, in detecting lytic foci obscured
      by other structures or with a small degree of destruction was seen. A potentially
      increased specificity of CT was found in detecting cases of small foci suspicious
      of lytic lesions on skull radiographs, seen as arachnoid granulations fovea in
      CT. The following radiation parameters were recorded: max. CTDIvol - 7.4 mGy and
      DLP - 660-810 mGy*cm. WBLDCT was much shorter and more convenient to patients.
      CONCLUSIONS: WBLDCT may become a valuable part of the assessment of MM features
      at a much lower radiation dose compared to standard CT protocols. It has a
      potential ability to increase diagnostic accuracy compared to radiography.

PMID- 28740566
TI  - Salvage Embolization and Histologic Analysis of Gastric Cancer with Hemorrhagic
      Shock Using Spherical Embolic Material.
AB  - BACKGROUND: In a recent study, it was reported that transcatheter arterial
      embolization with spherical embolic material for life-threatening hemorrhages in
      various cancer patients was safe and effective. Calibrated microspheres are able
      to access distal regions of the target arteries, which results in the
      disappearance of tumor staining. However, there are few reports on the
      pathological behavior of EmboSpheres in gastric cancer specimens. In this case,
      we succeeded in salvage embolization for advanced gastric cancer with hemorrhagic
      shock using spherical embolic material. To our knowledge, this is the first
      report of a pathological evaluation of spherical embolic microspheres in a
      gastric cancer specimen. CASE REPORT: A 70-year-old man with scirrhous gastric
      cancer was admitted to our hospital for staging laparoscopy. Unfortunately, he
      had a sudden onset of hematemesis and melena leading to hemorrhagic shock due to
      bleeding from the gastric cancer. While undergoing a rapid blood transfusion, he
      underwent emergent embolization to achieve hemostasis. The left gastric and right
      gastroepiploic arteries were embolized with spherical embolic material, and the
      patient survived. Two days later, the patient was able to undergo gastrectomy. A
      large number of microspheres were observed in areas of hemorrhage. The range and
      median diameter of the minor axis were 177-1048 MUm and 281 MUm, respectively.
      CONCLUSIONS: Transcatheter arterial embolization using spherical embolic material
      could become one of safe and effective options, especially when there is no
      extravasation or pseudoaneurysm but only tumor staining from the clinical and
      pathological point of view.

PMID- 28740567
TI  - Pathophysiology of the Underactive Bladder: Evolving New Concepts.
AB  - PURPOSE OF REVIEW: Underactive Bladder (UAB) is an emerging concept of voiding
      dysfunction, building on a tradition of often overlapping and confusing
      terminologies describing the patient experience, urodynamic function, and
      pathophysiology. This confusion of symptoms with function with pathology has
      hampered development of an effective disease model. RECENT FINDINGS: As with
      other urinary symptoms, the relationship of voiding symptoms to urodynamic
      dysfunction is variable. Efforts are underway to formally define UAB as a
      collection of symptoms related to voiding. Defined as voiding symptoms, UAB
      cannot be reliably linked to detrusor underactivity (DU) nor to detrusor
      weakness. SUMMARY: Progress will be made by characterizing the functional
      disorders underlying UAB symptoms, examining the biology of these linkages, re
      conceptualizing urinary control as one part of a more global biologic adaptive
      physiology, and determining the relationships of central and peripheral
      pathologies leading to disrupted control mechanisms.

PMID- 28740568
TI  - Methane Suppresses Microglial Activation Related to Oxidative, Inflammatory, and
      Apoptotic Injury during Spinal Cord Injury in Rats.
AB  - OBJECTIVE: We investigated the hypothesis that methane-rich saline (MS) can be
      used to repair spinal cord injury (SCI) in a rat model through suppressing
      microglial activation related to oxidative, inflammatory, and apoptotic injury.
      METHODS: MS was injected intraperitoneally in rats after SCI. Hematoxylin-eosin
      (HE) staining, oxidative stress, inflammatory parameters, and cell apoptosis were
      detected 72 h after SCI to determine the optimal dose. Then, we investigated the
      protective mechanisms and the long-term effects of MS on SCI. HE and microglial
      activation were observed. Neurological function was evaluated by the Basso,
      Beattie, and Bresnahan (BBB) scale. RESULTS: MS can significantly decrease
      infarct area and inhibit oxidative stress, inflammation, and cell apoptosis 72 h
      following SCI. The MS protective effect at a dose of 20 ml/kg was better.
      Moreover, MS can significantly suppress microglial activation related to
      oxidative and inflammatory injury after SCI and improve hind limb neurological
      function. CONCLUSION: MS could repair SCI and reduce the release of oxidative
      stress, inflammatory cytokines, and cell apoptosis produced by activated
      microglia. MS provides a novel and promising strategy for the treatment of SCI.

PMID- 28740569
TI  - DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant
      Epigenetic Alterations.
AB  - Approximately 20% of human cancers is attributable to DNA oncogenic viruses such
      as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus
      (EBV). Unrepaired DNA damage is the most common and overlapping feature of these
      DNA oncogenic viruses and a source of genomic instability and tumour development.
      Sustained DNA damage results from unceasing production of reactive oxygen species
      and activation of inflammasome cascades that trigger genomic changes and
      increased propensity of epigenetic alterations. Accumulation of epigenetic
      alterations may interfere with genome-wide cellular signalling machineries and
      promote malignant transformation leading to cancer development. Untangling and
      understanding the underlying mechanisms that promote these detrimental effects
      remain the major objectives for ongoing research and hope for effective virus
      induced cancer therapy. Here, we review current literature with an emphasis on
      how DNA damage influences HPV, HVB, and EBV replication and epigenetic
      alterations that are associated with carcinogenesis.

PMID- 28740570
TI  - Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical
      Carcinogenesis.
AB  - Quercetin is a flavonoid widely studied as a chemopreventive agent in different
      types of cancer. Previously, we reported that quercetin has a chemopreventive
      effect on the liver-induced preneoplastic lesions in rats. Here, we evaluated if
      quercetin was able not only to prevent but also to reverse rat liver
      preneoplastic lesions. We used the modified resistant hepatocyte model (MRHM) to
      evaluate this possibility. Treatment with quercetin was used 15 days after the
      induction of preneoplastic lesions. We found that quercetin reverses the number
      of preneoplastic lesions and their areas. Our results showed that quercetin
      downregulates the expression of EGFR and modulates this signaling pathway in
      spite of the activated status of EGFR as detected by the upregulation of this
      receptor, with respect to that observed in control rats. Besides, quercetin
      affects the phosphorylation status of Src-1, STAT5, and Sp-1. The better status
      of the liver after the treatment with quercetin could also be confirmed by the
      recovery in the expression of IGF-1. In conclusion, we suggest that quercetin
      reversed preneoplastic lesions by EGFR modulation and the activation state of
      Src, STAT5, and Sp1, so as the basal IGF-1.

PMID- 28740571
TI  - Comparison of the Neuroprotective and Anti-Inflammatory Effects of the
      Anthocyanin Metabolites, Protocatechuic Acid and 4-Hydroxybenzoic Acid.
AB  - Anthocyanins are being increasingly investigated for their neuroprotective and
      antineuroinflammatory effects; however, the overall bioavailability of many
      anthocyanins is relatively low. In contrast, phenolic acids, metabolites of many
      polyphenols, including anthocyanins, have been shown to accumulate in tissue at
      higher concentrations than those of parent compounds, suggesting that these
      metabolites may be the bioactive components of anthocyanin-rich diets. We
      examined the neuroprotective capacity of two common phenolic acids, 4
      hydroxybenzoic acid (HBA) and protocatechuic acid (PCA), in primary cultures of
      cerebellar granule neurons. Both HBA and PCA are capable of mitigating oxidative
      stress induced by hydrogen peroxide, which is thought to contribute to neuronal
      cell death in neurodegeneration. Under conditions of nitrosative stress, which
      occur during inflammation in the central nervous system, only PCA was
      neuroprotective, despite similar structural characteristics between HBA and PCA.
      Intriguingly, this trend was reversed under conditions of excitotoxicity, in
      which only HBA was neuroprotective. Lastly, we explored the anti-inflammatory
      activity of these compounds in microglial cells stimulated with
      lipopolysaccharide. PCA was an effective anti-inflammatory agent, reducing nitric
      oxide production, while HBA had no effect. These data indicate that phenolic
      acids possess distinct neuroprotective and anti-inflammatory characteristics that
      could make them suitable for the treatment of neurodegeneration.

PMID- 28740572
TI  - Effect of Whole-Body Cryotherapy on Antioxidant Systems in Experimental Rat
      Model.
AB  - BACKGROUND: The purpose of this study was to verify the effect of whole-body
      cryotherapy (WBC) in rats on their antioxidant systems, lipid peroxidation
      products, and their total oxidative status at different exposure times and
      temperatures. METHODS: Antioxidants in serum, plasma, liver, and erythrocytes
      were evaluated in two study groups following 1 min of exposure to -60 degrees C
      and -90 degrees C, for 5 and 10 consecutive days. RESULTS: WBC increased the
      activity of superoxide dismutase, catalase in the group subjected to 5 and 10
      days exposure, -60 degrees C. The glutathione S-transferase activity increased in
      the groups subjected to 10 days WBC sessions. Total antioxidant capacity
      increased after 5 and 10 days of 1 min WBC, -60 degrees C; a decrease was
      observed at -90 degrees C. A decreased level of erythrocyte malondialdehyde
      concentration was observed at -60 degrees C after 5 and 10 days of
      cryostimulation. An increased concentration was measured at -90 degrees C after
      10 days, and increase of erythrocyte malondialdehyde concentration after 5 days, 
      90 degrees C. CONCLUSIONS: To the best of our knowledge, this is the first
      research showing the effect of WBC in rats at different exposure times and
      temperatures. The effect of cryotherapy on enzymatic and nonenzymatic antioxidant
      systems was observed in the serum of animals exposed to a temperature of -60
      degrees C in comparison to control.

PMID- 28740573
TI  - Telomere length regulation through epidermal growth factor receptor signaling in
      cancer.
AB  - Length of the telomere (TL), a structure at the tip of chromosome that protects
      and ensures stability, is determined by multi-protein complexes such as
      telosome/shelterin and telomerase. Earlier studies from our laboratory show that
      longer TL has potential to be positive predictive biomarker of clinical outcome
      to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy in
      patients with KRAS WT metastatic colorectal cancer. Although there is extensive
      literature suggesting the role of shelterin and telomerase, not much literature
      exists that describes the role of EGFR and KRAS pathway in regulating TL. This
      detailed review focuses on an insight into various components, including
      proteins, enzymes and transcription factors, interlinking between EGFR pathways
      and telomerase that regulate TL.

PMID- 28740574
TI  - Phase I/II study of erlotinib, carboplatin, pemetrexed, and bevacizumab in
      chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer
      harboring epidermal growth factor receptor mutation.
AB  - BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors
      significantly prolong the progression-free survival of patients with non-squamous
      non-small cell lung cancer (NSCLC). However, most patients develop tumor regrowth
      and their prognosis remains poor. A new treatment strategy for NSCLC harboring
      EGFR mutation is therefore necessary. METHODS: In phase I, eligible patients were
      administered oral erlotinib daily and intravenous pemetrexed, carboplatin, and
      bevacizumab every 3 weeks for four cycles with maintenance of pemetrexed and
      bevacizumab until progressive disease was observed. The dose of erlotinib was 100
      mg for dose level 1 and 150 mg for dose level 2. The doses of pemetrexed,
      carboplatin, and bevacizumab were fixed at 500 mg/m2, area under the
      concentration-time curve of 6 mg/mL . min, and 15 mg/kg, respectively. The dose
      limiting toxicities were grade 3/4 neutropenia with fever or infection, grade 4
      leukopenia lasting for >=7 days, grade 4 thrombocytopenia, grade 3/4
      uncontrollable nonhematological toxicity, and delayed administration of the
      subsequent cycle by >2 weeks because of adverse events. RESULTS: Six patients
      were enrolled in phase I (dose level 1, n = 3; dose level 2, n = 3). During the
      induction phase, grade 3 neutropenia without fever was observed in one patient at
      dose level 1 and two patients at dose level 2. Grade 3 anemia was reported in one
      patient at dose level 1 and grade 3 thrombocytopenia was reported in two patients
      at dose level 1 and dose level 2, respectively. CONCLUSION: Four-drug combination
      therapy is a feasible and promising.

PMID- 28740575
TI  - Identification of novel diagnostic and prognostic miRNA signatures in endometrial
      cancer.
AB  - With the goal of identifying diagnostic and prognostic biomarkers in endometrial
      cancer, miRNA-profiling was carried out with formalin-fixed paraffin embedded
      (FFPE) tissue samples from 49 endometrial cancer patients. Results using an 84
      cancer specific miRNA panel identified the upregulation of miR-141-3p and miR-96
      5p along with a downregulation of miR-26, miR-126-3p, miR-23b, miR-195-5p, miR
      374a and let-7 family of miRNAs in endometrial cancer. We validated the
      dysregulated expression of the identified miRNAs in a panel of endometrial cancer
      cell-lines. Immunohistochemical analysis of the tissue micro array derived from
      these patients established the functional correlation between the decreased
      expression of tumor suppressive miRNAs and their target oncogenes: ERBB2, EGFR,
      EPHA2, BAX, GNA12, GNA13, and JUN. Comparative analysis of the samples from the
      patients with extended progression-free survival (PFS) ( > 21 months) versus the
      patients with the PFS of < 21 months indicated increased expression of tumor
      suppressive miR-142-3p, miR-142-5p, and miR-15a-5p in samples from extended PFS
      patients. In addition to defining a specific set of miRNAs and their target genes
      as potential diagnostic biomarkers, our studies have identified tumor suppressive
      miR-142 cluster and miR-15a as predictors of favorable prognosis for therapy
      response in endometrial cancer.

PMID- 28740576
TI  - The chemokine scavenging receptor D6/ACKR2 is a target of miR-146a in thyroid
      cancer.
AB  - We have previously shown that miR-146a, a NF-kappaB-regulated microRNA, is
      strongly expressed in human specimens and cell lines derived from anaplastic
      thyroid carcinomas (ATC) where it mediates some of the NF-kappaB pro-tumorigenic
      functions. By using a bioinformatic analysis, we identified the chemokine
      scavenger receptor D6/ ACKR2 as a target of miR146a in human ATC. We found that
      the expression of D6/ ACKR2 was up-regulated in miR-146a-null ATC cell lines and
      that the 3' UTR of D6/ ACKR2 mRNA was able to inhibit its expression in parental,
      but not in miR-146a-null ATC cells. Since human specimens from primary ATC showed
      a low expression of D6/ ACKR2 compared to normal thyroid tissues, we analyzed the
      effects of D6/ACKR2 over-expression in ATC cells. Different chemokines added to
      the conditioned medium of D6/ACKR2 over-expressing ATC cells partially failed to
      drive in vitro monocyte migration, and tumors derived from the injection of the
      same cells in nude mice showed a decreased number of infiltrating macrophages.
      Taken together, these results indicate that ATC cells down-regulate D6/ACKR2
      expression through miR-146a activity to sustain leukocyte trafficking inside
      tumor microenvironment and shed light on a novel mechanism by which NF-kappaB
      indirectly inhibits the expression and the function of anti-tumorigenic gene in
      thyroid cancer.

PMID- 28740577
TI  - EGFR as a prognostic biomarker and therapeutic target in ovarian cancer:
      evaluation of patient cohort and literature review.
AB  - BACKGROUND: Limited effectiveness of therapeutic agents targeting epidermal
      growth factor receptor (EGFR) in clinical trials using unselected ovarian cancer
      patients has prompted efforts to more effectively stratify patients who might
      best benefit from these therapies. A series of studies that have evaluated
      immunohistochemical (IHC) staining of EGFR in ovarian cancer biopsies has
      produced unclear results as to the utility of this measure as a prognostic
      biomarker. Here, we used one of the largest, single institution cohorts to date
      to determine possible associations of EGFR expression with patient outcome.
      METHODS: We performed IHC staining of EGFR in tissue microarrays including nearly
      500 patient tumor samples. Staining was classified by subcellular localization
      (membranous, cytoplasmic) or by automated image analysis algorithms. We also
      performed a literature review to place these results in the context of previous
      studies. RESULTS: No significant associations were found between EGFR subcellular
      localization or expression and histology, stage, grade, or outcome. These results
      were broadly consistent with the consensus of the reviewed literature.
      CONCLUSIONS: These results suggest that IHC staining for EGFR may not be a useful
      prognostic biomarker for ovarian cancer patients. Future studies should pursue
      other staining methods or analysis in combination with other pathway mediators.

PMID- 28740578
TI  - Clinical performance of E2Fs 1-3 in kidney clear cell renal cancer, evidence from
      bioinformatics analysis.
AB  - Extensive research on the E2F transcription factor family has led to numerous
      insights that E2Fs were involved not only in proliferation and tumorigenesis but
      also in apoptosis and differentiation. In the present study, we analyzed the
      differential expression of E2Fs1-3 genes, and also evaluated the impact of E2Fs 1
      3 genes expression on clinical outcome from the Cancer Genome Atlas (TCGA)
      database. The results showed that E2F1, E2F2 and E2F3 expression was increased in
      KIRC tissues than matched normal tissues (E2F1, P < 0.001; E2F2, P < 0.001, E2F3,
      P = 0.001), respectively. E2F1, E2F2 and E2F3 were significantly different in
      metastasis status, lymph node status, stage, and T stage in KIRC patients (all P
      < 0.01). E2F1 and E2F2 had the sensitivity of 96.1% and 93.1% and the specificity
      of 87.2% and 91.7% in discriminating KIRC from normal controls. High E2F1, E2F2
      and E2F3 expression were correlated to worsen overall survival (all P < 0.01),
      and high E2F3 expression had worse disease free survival (P = 0.0404).
      Multivariate Cox regression analysis revealed that E2F1 and E2F3 were independent
      prognostic factors for overall survival. Taken together, E2F1 and E2F2 may serve
      as valuable diagnostic markers for KIRC. Moreover, E2F1, E2F2 and E2F3 could
      provide valuable prognostic information for KIRC patients.

PMID- 28740579
TI  - Guest Editors Richard Robbins and Steven Petak Provide Oversight & Expertise for
      Special Issue on Hormones and the Heart.

PMID- 28740580
TI  - Hormones and the Heart.

PMID- 28740581
TI  - The Parathyroid Gland and Heart Disease.
AB  - The parathyroid glands are critical to maintaining calcium homeostasis through
      actions of parathyroid hormone (PTH). Recent clinical and molecular research has
      shown that direct and indirect actions of PTH also affect the heart and
      vasculature through downstream actions of G protein-coupled receptors in the
      myocardium and endothelial cells. Patients with disorders of the parathyroid
      gland have higher incidences of hypertension, arrhythmias, left ventricular
      hypertrophy, heart failure, and calcific disease which translate into increased
      cardiac morbidity and mortality. Importantly, clinical research also suggests
      that early treatment of parathyroid disorders through medical or surgical
      management may reverse cardiovascular remodeling and mitigate cardiac risk
      factors.

PMID- 28740582
TI  - Hypothyroidism and the Heart.
AB  - Hypothyroidism is a commonly encountered clinical condition with variable
      prevalence. It has profound effects on cardiac function that can impact cardiac
      contractility, vascular resistance, blood pressure, and heart rhythm. With this
      review, we aim to describe the effects of hypothyroidism and subclinical
      hypothyroidism on the heart. Additionally, we attempt to briefly describe how
      hypothyroid treatment affects cardiovascular parameters.

PMID- 28740583
TI  - Hyperthyroidism and the Heart.
AB  - Thyroid hormones have a significant impact on cardiac function and structure.
      Excess thyroid hormone affects cardiovascular hemodynamics, leading to high
      output heart failure and, in late stages, dilated cardiomyopathy. In this review,
      we discuss how hyperthyroidism affects cardiovascular pathophysiology and
      molecular mechanisms and examine the complications caused by excess thyroid
      hormone, such as heart failure and atrial fibrillation.

PMID- 28740584
TI  - Cardiovascular Disease in Acromegaly.
AB  - In patients with acromegaly, chronic excess of growth hormone (GH) and insulin
      like growth factor-1 (IGF-1) leads to the development of acromegalic
      cardiomyopathy. Its main features are biventricular hypertrophy, diastolic
      dysfunction, and in later stages, systolic dysfunction and congestive heart
      failure. Surgical and/or pharmacological treatment of acromegaly and control of
      cardiovascular risk factors help reverse some of these pathophysiologic changes
      and decrease the high risk of cardiovascular complications.

PMID- 28740585
TI  - Testosterone and the Heart.
AB  - Testosterone (T) has a number of important effects on the cardiovascular system.
      In men, T levels begin to decrease after age 40, and this decrease has been
      associated with an increase in all-cause mortality and cardiovascular (CV) risk.
      Low T levels in men may increase their risk of developing coronary artery disease
      (CAD), metabolic syndrome, and type 2 diabetes. Reduced T levels in men with
      congestive heart failure (CHF) portends a poor prognosis and is associated with
      increased mortality. Studies have reported a reduced CV risk with higher
      endogenous T concentration, improvement of known CV risk factors with T therapy,
      and reduced mortality in T-deficient men who underwent T replacement therapy
      versus untreated men. Testosterone replacement therapy (TRT) has been shown to
      improve myocardial ischemia in men with CAD, improve exercise capacity in
      patients with CHF, and improve serum glucose levels, HbA1c, and insulin
      resistance in men with diabetes and prediabetes. There are no large long-term,
      placebo-controlled, randomized clinical trials to provide definitive conclusions
      about TRT and CV risk. However, there currently is no credible evidence that T
      therapy increases CV risk and substantial evidence that it does not. In fact,
      existing data suggests that T therapy may offer CV benefits to men.

PMID- 28740586
TI  - Mechanical Valve Thrombosis on Rivaroxaban: Are Novel Anticoagulants Really an
      Option?
AB  - This is a case of a 54-year-old female with a history of mechanical aortic valve
      replacement who presented in cardiogenic shock. Her primary care provider started
      her on rivaroxaban for anticoagulation therapy. An urgent transesophageal
      echocardiogram revealed a significant gradient and thrombosis on one leaflet of
      the valve that was immobile. Given that she was not a surgical candidate, she
      underwent thrombolysis. However, she later died due to complications from the
      thrombotic valve. The utility of target-specific oral anticoagulants has yet to
      be established in clinical practice.

PMID- 28740587
TI  - Complications of Varicella Zoster Infection of the Central Nervous System.

PMID- 28740588
TI  - Coronary Artery Fistula.
AB  - Coronary artery fistulae are rare abnormalities of the coronary arteries that are
      usually discovered incidentally on coronary angiogram. Most patients remain
      asymptomatic, and significant hemodynamic consequences are rarely observed. The
      following report describes the case of a patient presenting with symptoms of
      congestive cardiac failure due to multiple coronary artery fistulae.

PMID- 28740589
TI  - Left Atrial Intramural Hematoma After Surgical Aortic Valve Replacement.

PMID- 28740591
TI  - To Autumn.

PMID- 28740590
TI  - Updates on the Management of Severe Asthma.

PMID- 28740592
TI  - Art and Medicine with Dr. Phil.

PMID- 28740593
TI  - Hearing is Believing.

PMID- 28740594
TI  - Opportunities for treatment of the hepatitis C virus-infected patient with
      chronic kidney disease.
AB  - The prevalence of hepatitis C virus (HCV) infection amongst patients with chronic
      kidney disease (CKD) and end-stage renal disease exceeds that of the general
      population. In addition to predisposing to the development of cirrhosis and
      hepatocellular carcinoma, infection with HCV has been associated with extra
      hepatic complications including CKD, proteinuria, glomerulonephritis,
      cryoglobulinemia, increased cardiovascular risk, insulin resistance, and
      lymphoma. With these associated morbidities, infection with HCV is not
      unexpectedly accompanied by an increase in mortality in the general population as
      well as in patients with kidney disease. Advances in the understanding of the HCV
      genome have resulted in the development of direct-acting antiviral agents that
      can achieve much higher sustained virologic response rates than previous
      interferon-based protocols. The direct acting antivirals have either primarily
      hepatic or renal metabolism and excretion pathways. This information is
      particularly relevant when considering treatment in patients with reduced kidney
      function. In this context, some of these agents are not recommended for use in
      patients with a glomerular filtration rate < 30 mL/min per 1.73 m2. There are now
      Food and Drug Administration approved direct acting antiviral agents for the
      treatment of patients with kidney disease and reduced function. These agents have
      been demonstrated to be effective with sustained viral response rates comparable
      to the general population with good safety profiles. A disease that was only
      recently considered to be very challenging to treat in patients with kidney
      dysfunction is now curable with these medications.

PMID- 28740595
TI  - Imaging guided percutaneous interventions in hepatic dome lesions: Tips and
      tricks.
AB  - Percutaneous hepatic interventions are generally safe given the fact that liver
      closely abuts the abdominal wall and hence it is easily accessible. However, the
      superior portion of liver, adjacent to the diaphragm, commonly referred as the
      "hepatic dome", presents unique challenges for interventionists. Percutaneous
      access to the hepatic dome may be restricted by anatomical factors and special
      considerations may be required to avoid injury to the surrounding organs. The
      purpose of this review article is to discuss certain specific maneuvers and
      techniques that can enhance the success and safety of interventions in the
      hepatic dome.

PMID- 28740596
TI  - Improved Hepascore in hepatitis C predicts reversal in risk of adverse outcome.
AB  - AIM: To establish if serial Hepascore tests (referred to as delta Hepascore) in
      those with chronic hepatitis C (CHC) correlate with the increase and/or decrease
      in risk of liver related complications. METHODS: Three hundred and forty-six CHC
      patients who had two Hepascore tests performed were studied. During 1944 patient
      years follow-up 28 (8.1%) reached an endpoint. The Hepascore is a serum test that
      provides clinically useful data regarding the stage of liver fibrosis and
      subsequent clinical outcomes in chronic liver disease. RESULTS: Patients with a
      baseline Hepascore > 0.75 had a significantly increased rate of reaching a
      composite endpoint consisting of hepatocellular carcinoma, liver death, and/or
      decompensation (P < 0.001). In those with an initial Hepascore > 0.75, a
      subsequent improved Hepascore showed a significantly decreased risk for the
      composite endpoint (P = 0.004). There were no negative outcomes in those with a
      stable or improved delta Hepascore. The minimum time between tests that was found
      to give a statically significant result was in those greater than one year (P =
      0.03). CONCLUSION: In conclusion, Hepascore is an accurate predictor of liver
      related mortality and liver related morbidity in CHC patients. Of note, we have
      found that there is a decreased risk of mortality and morbidity in CHC patients
      when the patient has an improving delta Hepascore. Repeat Hepascore tests, when
      performed at a minimum one-year interval, may be of value in routine clinical
      practice to predict liver related clinical outcomes and to guide patient
      management.

PMID- 28740597
TI  - Is hepatic steatosis associated with left ventricular mass index increase in the
      general population?
AB  - AIM: To investigate the association between hepatic steatosis and change in left
      ventricular mass index (LVMI) over five years, and examine whether systolic and
      diastolic blood pressures are mediators of the association between hepatic
      steatosis and LVMI using a general population sample. METHODS: We analyzed data
      from the Study of Health in Pomerania. The study population comprised 1298
      individuals aged 45 to 81 years. Hepatic steatosis was defined as the presence of
      a hyperechogenic pattern of the liver together with elevated serum alanine
      transferase levels. Left ventricular mass was determined echocardiographically
      and indexed to height2.7. Path analyses were conducted to differentiate direct
      and indirect paths from hepatic steatosis to LVMI encompassing systolic and
      diastolic blood pressure as potential mediating variables. RESULTS: Hepatic
      steatosis was a significant predictor for all measured echocardiographic
      characteristics at baseline. Path analyses revealed that the association of
      hepatic steatosis with LVMI change after five years was negligibly small (beta = 
      0.12, s.e. = 0.21, P = 0.55). Systolic blood pressure at baseline was inversely
      associated with LVMI change (beta = -0.09, s.e. = 0.03, P < 0.01), while no
      association between diastolic blood pressure at baseline and LVMI change was
      evident (beta = 0.03, s.e. = 0.05, P = 0.56). The effect of the indirect path
      from hepatic steatosis to LVMI via systolic baseline blood pressure was small
      (beta = -0.20, s.e. = 0.10, P = 0.07). No indirect effect was observed for the
      path via diastolic baseline blood pressure (beta = 0.03, s.e. = 0.06, P = 0.60).
      Similar associations were observed in the subgroup of individuals not receiving
      beta-blockers, calcium channel blockers, or drugs acting on the renin-angiotensin
      system. CONCLUSION: Baseline associations between hepatic steatosis and LVMI do
      not extend to associations with LVMI change after five years. More studies are
      needed to study the longitudinal effects of hepatic steatosis on LVMI.

PMID- 28740598
TI  - Taking Pharmaceutical Innovation to the Masses.
AB  - General levels of "pharmaceuticals literacy" are not high in contemporary
      societies. To address this educational need, in 2012 the University of Western
      Australia introduced an innovative multidisciplinary course for undergraduates
      within any degree program entitled PHAR1101: Drugs that Changed the World. Now
      ranking among the largest courses at the institution, PHAR1101 enrollments will
      likely approach 1000 students in 2017.

PMID- 28740599
TI  - Biosimilars: Imitation Games.
AB  - Biopharmaceutical sales were at $160 billion in 2016. With many top revenue
      biopharmaceuticals coming off patent in the next 4 years, there is a tremendous
      rush by leading biopharmaceutical companies worldwide to launch biosimilar
      versions of innovator products. However, these protein drugs are extremely
      difficult to copy. In this viewpoint, we will discuss the various drugs slated to
      lose patent protection and the challenges in manufacturing these drugs using
      current technologies. The Food and Drug Administration's regulatory role and
      definitions of similarity will be discussed, and finally, the scientific
      challenges in mimicking a protein drug in the current patent- and innovation
      driven research field will be considered.

PMID- 28740600
TI  - Seeking (and Finding) Biased Ligands of the Kappa Opioid Receptor.
AB  - The discovery and characterization of two classes of kappa opioid receptor
      agonists that are biased for G protein over betaarrestin signaling are described.

PMID- 28740601
TI  - Synthesis and Evaluation of a Linkable Functional Group-Equipped Analogue of the
      Epothilones.
AB  - An approach to the validation of a linker strategy for the epothilone family of
      microtubule-stabilizing agents is reported. An analogue of epothilone B in which
      the C(6) methyl group has been replaced with a 4-azidobutyl group has been
      prepared by total chemical synthesis, and amides derived from the azido group
      have been shown to retain the activity of the parent compound. These results set
      the stage for an evaluation of the potential of the epothilones to serve as the
      drug component of antibody-drug conjugates and other selective tumor cell
      targeting conjugates.

PMID- 28740602
TI  - Discovery of the Antitumor Effects of a Porphyrazine Diol (Pz 285) in MDA-MB-231
      Breast Tumor Xenograft Models in Mice.
AB  - A series of porphyrazines (Pzs) with chiral bis-acetal moieties in the beta
      pyrrole positions ((2R,3R)-2,3-dimethyl-2,3-dimethoxy-1,4-diox-2-ene) have been
      synthesized and screened as antitumor agents in MDA-MB-231 breast tumor cells in
      vitro. The lead Pz 285 was further tested in a mouse tumor xenograft model with
      Td-tomato-luc2 fluorescent breast tumor cells (MDA-MB-231 LM24 Her2+) that are
      highly metastatic to the lungs. Pz 285 shows marked antitumor effects in vivo,
      with treated mice exhibiting longer median survival that we attribute to smaller
      primary tumor regrowth after resection and less occurrence of metastasis when
      compared to vehicle control groups. Pz 285 is further compared to the clinically
      approved chemotherapeutic doxorubicin (Dox). This report lays the groundwork for
      development of an understudied class of compounds for classical chemotherapy.

PMID- 28740603
TI  - An ATR-FTIR Sensor Unraveling the Drug Intervention of Methylene Blue, Congo Red,
      and Berberine on Human Tau and Abeta.
AB  - Alzheimer's disease affects millions of human beings worldwide. The disease
      progression is characterized by the formation of plaques and neurofibrillary
      tangles in the brain, which are based on aggregation processes of the Abeta
      peptide and tau protein. Today there is no cure and even no in vitro assay
      available for the identification of drug candidates, which provides direct
      information concerning the protein secondary structure label-free. Therefore, we
      developed an attenuated total reflection Fourier transform infrared spectroscopy
      (ATR-FTIR) sensor, which uses surface bound antibodies to immobilize a desired
      target protein. The secondary structure of the protein can be evaluated based on
      the secondary structure sensitive frequency of the amide I band. Direct
      information about the effect of a drug candidate on the secondary structure
      distribution of the total target protein fraction within the respective body
      fluid can be detected by a frequency shift of the amide I band. Thereby, the
      extent of the amide I shift is indicative for the compound efficiency. The
      functionality of this approach was demonstrated by the quantification of the
      effect of the drug candidate methylene blue on the pathogenic misfolded tau
      protein as extracted from cerebrospinal fluid (CSF). Methylene blue induces a
      shift from pathogenic folded beta-sheet dominated to the healthy monomeric state.
      A similar effect was observed for congo red on pathogenic Abeta isoforms from
      CSF. In addition, the effect of berberine on synthetic Abeta1-42 is studied.
      Berberine seems to decelerate the aggregation process of synthetic Abeta1-42
      peptides.

PMID- 28740604
TI  - Identification of a Novel TRPM8 Agonist from Nutmeg: A Promising Cooling
      Compound.
AB  - The transient receptor potential melastatin 8 (TRPM8) ion channel is the primary
      receptor for innocuous cold stimuli (<28  degrees C) in humans. TRPM8 agonists
      such as l-(-)-menthol are widely used as flavors and additives to impart
      briskness, in addition to medicinal uses for inflammation and pain. Though
      various natural and synthetic agonists have been explored, only few natural
      compounds are known. We report herein the identification and characterization of
      the novel neolignan agonist erythro- and threo-Delta8'-7-ethoxy-4-hydroxy-3,3',5'
      trimethoxy-8-O-4'-neolignan (1) with an EC50 of 0.332 MUM, which was isolated
      from a well-known spice, nutmeg (Myristica fragrans Houtt.). Structure activity
      relationships are also disclosed, showing that the 7-d-menthoxy derivative is the
      most potent agonist (EC50 = 11 nM). The combination of 1 and l-(-)-menthol has an
      additive effect, suggesting that neolignan compounds interact with TRPM8 at
      different sites from those of l-(-)-menthol.

PMID- 28740605
TI  - Synthesis of a Fluorescently Labeled 68Ga-DOTA-TOC Analog for Somatostatin
      Receptor Targeting.
AB  - Fluorescently labeled imaging agents can identify surgical margins in real-time
      to help achieve complete resections and minimize the likelihood of local
      recurrence. However, photon attenuation limits fluorescence-based imaging to
      superficial lesions or lesions that are a few millimeters beneath the tissue
      surface. Contrast agents that are dual-labeled with a radionuclide and
      fluorescent dye can overcome this limitation and combine quantitative, whole-body
      nuclear imaging with intraoperative fluorescence imaging. Using a multimodality
      chelation (MMC) scaffold, IRDye 800CW was conjugated to the clinically used
      somatostatin analog, 68Ga-DOTA-TOC, to produce the dual-labeled analog, 68Ga
      MMC(IRDye 800CW)-TOC, with high yield and specific activity. In vitro
      pharmacological assays demonstrated retention of receptor-targeting properties
      for the dual-labeled compound with robust internalization that was somatostatin
      receptor (SSTR) 2-mediated. Biodistribution studies in mice identified the
      kidneys as the primary excretion route for 68Ga-MMC(IRDye 800CW)-TOC, along with
      clearance via the reticuloendothelial system. Higher uptake was observed in most
      tissues compared to 68Ga-DOTA-TOC but decreased as a function of time. The
      combination of excellent specificity for SSTR2-expressing cells and suitable
      biodistribution indicate potential application of 68Ga-MMC(IRDye 800CW)-TOC for
      intraoperative detection of SSTR2-expressing tumors.

PMID- 28740606
TI  - Structure-Guided Strategy for the Development of Potent Bivalent ERK Inhibitors.
AB  - ERK is the effector kinase of the RAS-RAF-MEK-ERK signaling cascade, which
      promotes cell transformation and malignancy in many cancers and is thus a major
      drug target in oncology. Kinase inhibitors targeting RAF or MEK are already used
      for the treatment of certain cancers, such as melanoma. Although the initial
      response to these drugs can be dramatic, development of drug resistance is a
      major challenge, even with combination therapies targeting both RAF and MEK.
      Importantly, most resistance mechanisms still rely on activation of the
      downstream effector kinase ERK, making it a promising target for drug development
      efforts. Here, we report the design and structural/functional characterization of
      a set of bivalent ERK inhibitors that combine a small molecule inhibitor that
      binds to the ATP-binding pocket with a peptide that selectively binds to an ERK
      protein interaction surface, the D-site recruitment site (DRS). Our studies show
      that the lead bivalent inhibitor, SBP3, has markedly improved potency compared to
      the small molecule inhibitor alone. Unexpectedly, we found that SBP3 also binds
      to several ERK-related kinases that contain a DRS, highlighting the importance of
      experimentally verifying the predicted specificity of bivalent inhibitors.
      However, SBP3 does not target any other kinases belonging to the same CMGC branch
      of the kinome. Additionally, our modular click chemistry inhibitor design
      facilitates the generation of different combinations of small molecule inhibitors
      with ERK-targeting peptides.

PMID- 28740607
TI  - Crystal Structure of a Human K-Ras G12D Mutant in Complex with GDP and the Cyclic
      Inhibitory Peptide KRpep-2d.
AB  - The Ras proteins play roles in cell differentiation, proliferation, and survival.
      Aberrant signaling through Ras-mediated pathways in tumor cells occurs as a
      result of several types of mutational damage, which most frequently affects the
      amino acids G12, G13, and Q61. Recently, KRpep-2d was identified as a K-Ras(G12D)
      selective inhibitory peptide against the G12D mutant of K-Ras, which is a key
      member of the Ras protein family and an attractive cancer therapeutic target. In
      this study, the crystal structure of the human K-Ras(G12D) mutant was determined
      in complex with GDP and KRpep-2d at 1.25 A resolution. This structure revealed
      that the peptide binds near Switch II and allosterically blocks protein-protein
      interactions with the guanine nucleotide exchange factor. This discovery of a
      unique binding pocket provides valuable information that will facilitate the
      design of direct Ras inhibitors.

PMID- 28740608
TI  - GNE-886: A Potent and Selective Inhibitor of the Cat Eye Syndrome Chromosome
      Region Candidate 2 Bromodomain (CECR2).
AB  - The biological function of bromodomains, epigenetic readers of acetylated lysine
      residues, remains largely unknown. Herein we report our efforts to discover a
      potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome
      region candidate 2 (CECR2). Screening of our internal medicinal chemistry
      collection led to the identification of a pyrrolopyridone chemical lead, and
      subsequent structure-based drug design led to a potent and selective CECR2
      bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound.

PMID- 28740609
TI  - Simple Tetrahydroisoquinolines Are Potent and Selective Kappa Opioid Receptor
      Antagonists.
AB  - Potent and selective kappa opioid receptor antagonists have been derived from the
      N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of pure
      opioid receptor antagonists. In order to determine if the 3-hydroxyphenyl and/or
      the piperidine amino groups are required for obtaining the pure opioid
      antagonists, (3R)-7-hydroxy-N-[(1S)-2-methyl-1-(piperidine-1-ylmethyl)propyl]
      1,2,3,4-tetrahydroiosquinoline-3-carboxamide (1), which does not have a 4-(3
      hydroxyphenyl) group, and (3R)-N-(1R)-1-(cyclohexylmethyl)-2-methylpropyl]-7
      hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (2), which does not have a 4
      hydroxylphenyl or a piperidine amino group, were synthesized and evaluated for
      their [35S]GTPgammaS binding properties at the MU, delta, and kappa opioid
      receptors. Surprisingly compound 1 remained a pure opioid antagonist with a Ke =
      6.80 nM at the kappa opioid receptor and is 21- and 441-fold selective for the
      kappa receptor relative to the MU and delta opioid receptors, respectively. Even
      more unexpected and novel is the finding that 2 has a Ke = 0.14 nM at kappa and
      is 1730- and 4570-fold selective for kappa relative to the MU and delta opioid
      receptors, respectively.

PMID- 28740610
TI  - Importance of a 4-Alkyl Substituent for Activity in the Englerin Series.
AB  - The ring closing metathesis/transannular etherification approach to the englerin
      nucleus was adapted to provide two key intermediates for analogue synthesis: the
      4-desmethyl Delta5,6 tricycle and the 4-oxo Delta5,6 tricycle. The former was
      elaborated to 4-desmethyl englerin A and the latter served as a common precursor
      for englerin A, 4-ethyl englerin A, and 4-isopropyl englerin A. 4-Desmethyl
      englerin A was less active than the natural product by an order of magnitude, but
      the 4-ethyl and 4-isopropyl analogues were comparable in activity to englerin A.
      These results are consistent with the premise that the 4-alkyl group enforces the
      binding conformation of the cinnamoyl ester substituent. Furthermore, they
      suggest that 4-alkyl englerin structures may prove to be useful tool compounds.

PMID- 28740611
TI  - Development of Potent Myostatin Inhibitory Peptides through Hydrophobic Residue
      Directed Structural Modification.
AB  - Myostatin, a negative regulator of skeletal muscle growth, is a promising target
      for treating muscle atrophic disorders. Recently, we discovered a minimal
      myostatin inhibitor 1 (WRQNTRYSRIEAIKIQILSKLRL-amide) derived from positions 21
      43 of the mouse myostatin prodomain. We previously identified key residues (N
      terminal Trp21, rodent-specific Tyr27, and all aliphatic amino acids) required
      for effective inhibition through structure-activity relationship (SAR) studies
      based on 1 and characterized a 3-fold more potent inhibitor 2 bearing a 2
      naphthyloxyacetyl group at position 21. Herein, we performed 1-based SAR studies
      focused on all aliphatic residues and Ala32, discovering that the incorporations
      of Trp and Ile at positions 32 and 38, respectively, enhanced the inhibitory
      activity. Combining these findings with 2, a novel peptide 3d displayed an IC50
      value of 0.32 MUM, which is 11 times more potent than 1. The peptide 3d would
      have the potential to be a promising drug lead to develop better peptidomimetics.

PMID- 28740612
TI  - 3-Hydroxykynurenine, a Tryptophan Metabolite Generated during the Infection, Is
      Active Against Trypanosoma cruzi.
AB  - The antiparasitic activity of 3-hydroxykynurenine (3-HK), one of the major
      tryptophan catabolites of the kynurenine pathway, against both Trypanosoma cruzi
      evolutive forms that are important for human infection, trypomastigotes (Tps) and
      amastigotes (Am), possible targets in the parasite and the drug toxicity to
      mammalian cells have been investigated. 3-HK showed a potent activity against Am
      with IC50 values in the micromolar concentration range, while the IC50 values to
      cause Tps death was ~6000-times higher, indicating that the replicative form
      present in the vertebrate hosts is much more susceptible to 3-HK than bloodstream
      Tps. In addition, 3-HK showed activity against Tps and Am, at concentrations that
      did not exhibit toxicity to mammalian cells. Ultrastructural analysis and flow
      cytometry studies indicated that Am and Tps mitochondrion and nuclei contain 3-HK
      targets. The potency and selectivity of 3-HK, which is generated during T. cruzi
      infection in human and mice, suggest that 3-HK may be a suitable candidate for
      drug research and development for Chagas disease.

PMID- 28740613
TI  - Synthesis and Biological Evaluation of Paclitaxel and Camptothecin Prodrugs on
      the Basis of 2-Nitroimidazole.
AB  - Due to the low esterase activity in human plasma, many ester and carbonate
      prodrugs tested in humans may be less effective than that in preclinical animals.
      In this letter, PTX and SN-38 were attached to the N-1 position of 2
      nitroimidazole via a carbonate linker. Presumably, 2-aminoimidazole may help
      promote the intramolecular hydrolysis of the carbonate bond. The prodrugs
      exhibited a considerable stability in buffers at different pH values as well as
      in human plasma. Furthermore, a rapid reduction was exhibited in the presence of
      nitroreductase. An in vitro cytotoxicity assay demonstrated that hypoxic
      conditions could increase the toxicity of prodrugs. Potentially, the compound
      species may form a new class of promising antitumor agents.

PMID- 28740614
TI  - New Class of Antitrypanosomal Agents Based on Imidazopyridines.
AB  - The present work describes the synthesis of 22 new imidazopyridine analogues
      arising from medicinal chemistry optimization at different sites on the molecule.
      Seven and 12 compounds exhibited an in vitro EC50 <= 1 MUM against Trypanosoma
      cruzi (T. cruzi) and Trypanosoma brucei (T. brucei) parasites, respectively.
      Based on promising results of in vitro activity (EC50 < 100 nM), cytotoxicity,
      metabolic stability, protein binding, and pharmacokinetics (PK) properties,
      compound 20 was selected as a candidate for in vivo efficacy studies. This
      compound was screened in an acute mouse model against T.cruzi (Tulahuen strain).
      After established infection, mice were dosed twice a day for 5 days, and then
      monitored for 6 weeks using an in vivo imaging system (IVIS). Compound 20
      demonstrated parasite inhibition comparable to the benznidazole treatment group.
      Compound 20 represents a potential lead for the development of drugs to treat
      trypanosomiasis.

PMID- 28740615
TI  - Improving Metabolic Stability with Deuterium: The Discovery of BMT-052, a Pan
      genotypic HCV NS5B Polymerase Inhibitor.
AB  - Iterative structure-activity analyses in a class of highly functionalized
      furo[2,3-b]pyridines led to the identification of the second generation pan
      genotypic hepatitis C virus NS5B polymerase primer grip inhibitor BMT-052 (14), a
      potential clinical candidate. The key challenge of poor metabolic stability was
      overcome by strategic incorporation of deuterium at potential metabolic soft
      spots. The preclinical profile and status of BMT-052 (14) is described.

PMID- 28740616
TI  - Unlocking the potential of established products: toward new incentives rewarding
      innovation in Europe.
AB  - Background: Many established products (EPs - marketed for eight years or more)
      are widely used off-label despite little evidence on benefit-risk ratio. This
      exposes patients to risks related to safety and lack of efficacy, and healthcare
      providers to liability. Introducing new indications for EPs may represent a high
      societal value; however, manufacturers rarely invest in R&D for EPs. The
      objective of this research was to describe incentives and disincentives for
      developing new indications for EPs in Europe and to investigate consequences of
      current policies. Methods: Targeted literature search and expert panel meetings.
      Results: Within the current European-level and national-level regulatory
      framework there are limited incentives for development of new indications with
      EPs. Extension of indication normally does not allow the price to be increased or
      maintained, the market protection period to be extended, or exclusion from a
      reference price system. New indication frequently triggers re-evaluation,
      resulting in price erosion, regardless of the level of added value with the new
      indication. In consequence, manufacturers are more prone to undertake R&D efforts
      at early to mid-stage of product life cycle rather than with EPs, or to invest in
      new chemical entities, even in therapeutic areas with broad off-label use. This
      represents a potentially missed opportunity as developing new indications for EPs
      offers an alternative to off-label use or lengthy and expensive R&D for new
      therapies, opens new opportunities for potentially cost-effective treatment
      alternatives, as well as greater equity in patients' access to treatment options.
      Conclusion: There are potential benefits from the development of new indications
      for EPs that are currently not being realized due to a lack of regulatory and
      pricing incentives in Europe. Incentives for orphan or paediatric drugs have
      proven to be effective in promoting R&D. Similarly, incentives to promote R&D in
      EPs should be developed, for the benefit of patients and healthcare systems.

PMID- 28740617
TI  - Supply-side and demand-side policies for biosimilars: an overview in 10 European
      member states.
AB  - OBJECTIVE: This study aimed to provide an overview of biosimilar policies in 10
      EU MSs. Methods: Ten EU MS pharmaceutical markets (Belgium, France, Germany,
      Greece, Hungary, Italy, Poland, Spain, Sweden, and the UK) were selected. A
      comprehensive literature review was performed to identify supply-side and demand
      side policies in place in the selected countries. Results: Supply-side policies
      for biosimilars commonly include price linkage, price re-evaluation, and
      tendering; the use of internal or external reference pricing varies between
      countries; health technology assessment is conducted in six countries. Regarding
      demand-side policies, pharmaceutical prescription budgets or quotas and
      monitoring of prescriptions (with potential financial incentives or penalties)
      are in place in eight and in seven countries respectively. Switching is generally
      allowed, but is solely the physician's responsibility. Automatic substitution is
      not recommended, or even forbidden, in most EU MSs. Prescription conditions or
      guidelines that apply to biosimilars are established in nearly all surveyed EU
      MSs. Conclusions: Important heterogeneity in policies on biosimilars was seen
      between (and even within) selected countries, which may partly explain variations
      in biosimilar uptake. Supply-side policies targeting price have been reported to
      limit biosimilar penetration in the long term, despite short-term savings, while
      demand-side policies are considered to positively impact uptake.

PMID- 28740618
TI  - Ethical issues associated with medical tourism in Africa.
AB  - Global disparities in medical technologies, laws, economic inequities, and social
      cultural differences drive medical tourism (MT), the practice of travelling to
      consume healthcare that is either too delayed, unavailable, unaffordable or
      legally proscribed at home. Africa is simultaneously a source and destination for
      MT. MT however, presents a new and challenging health ethics frontier, being
      largely unregulated and characterized by policy contradictions, minority
      discrimination and conflict of interest among role-players. This article assesses
      the level of knowledge of MT and its associated ethical issues in Africa; it also
      identifies critical research gaps on the subject in the region. Exploratory
      design guided by Arksey and O'Malley's (2005) framework was used. Key search
      terms and prior determined exclusion/inclusion criteria were used to identify
      relevant literature sources. Fifty-seven articles met the inclusion criteria.
      Distributive justice, healthcare resource allocation, experimental treatments and
      organ transplant were the most common ethical issues of medical tourism in
      Africa. The dearth of robust engagement of MT and healthcare ethics, as
      identified through this review, calls for more rigorous research on this subject.
      Although the bulk of the medical tourism industry is driven by global legal
      disparities based on ethical considerations, little attention has been given to
      this subject.

PMID- 28740619
TI  - Should new health technology be available only for patients able and willing to
      pay?
AB  - New health technology comes on the market at a rapid pace and - sometimes - at a
      huge cost. Providing access to new health technology is a serious challenge for
      many countries with mandatory health insurance. This article analyses access to
      new health technology in Belgium and the Netherlands, using eight concrete
      examples as a starting point for comparing the two - neighbouring - countries.
      Contrary to the Netherlands, out-of-pocket payments for new health technology are
      widely accepted and practiced in Belgium. This difference is largely the result
      of different regulatory environments. A major difference is the way that
      entitlements to care are described: closed and explicit in Belgium versus open
      and non-explicit in the Netherlands. The characteristics of in-kind policies
      versus reimbursement policies also play a role. Allowing out-of-pocket payments
      for new health technology has consequences for the patients. It leads to greater
      access to new health technology (for those who are able and willing to pay), but
      has a negative effect on equal access to care. Choice and transparency are
      enhanced by allowing out-of-pocket payments for new health technology. It could
      be argued that lack of coverage by mandatory health insurance should not render
      private access to new health technology impossible.

PMID- 28740620
TI  - Use and cost comparison of clobazam to other antiepileptic drugs for treatment of
      Lennox-Gastaut syndrome.
AB  - Background: Lennox-Gastaut syndrome (LGS) is a severe form of childhood-onset
      epilepsy associated with serious injuries due to frequent and severe seizures. Of
      the antiepileptic drugs (AEDs) approved for LGS, clobazam is a more recent market
      entrant, having been approved in October 2011. Recent AED budget impact and cost
      effectiveness analyses for LGS suggest that adding clobazam to a health plan
      formulary may result in decreased medical costs; however, research on clinical
      and economic outcomes and treatment patterns with these AED treatments in LGS is
      limited. Objectives: To compare the baseline characteristics and treatment
      patterns of new initiators of clobazam and other AEDs among LGS patients and
      compare healthcare utilization and costs before and after clobazam initiation
      among LGS patients. Methods: A retrospective study of probable LGS patients was
      conducted using the MarketScan(r) Commercial, Medicare Supplemental, and Medicaid
      databases (10/1/2010-3/31/2014). Results: In the Commercial/Medicare Supplemental
      population, clobazam users were younger, had fewer comorbidities, and more prior
      AED use than non-clobazam users. In the 12 months pre-treatment initiation,
      clobazam users had significantly more seizure-related inpatient stays and
      outpatient visits and higher total seizure-related (P < 0.001) and all-cause (P <
      0.001) costs than non-clobazam users. Among clobazam users, when compared to the
      12 months pre-clobazam initiation, seizure-related medical utilization and costs
      were lower in the 12 months post-clobazam initiation (P = 0.004). Total all-cause
      (P < 0.001) and seizure-related (P = 0.029) costs increased post-clobazam
      initiation mainly due to the increase in outpatient pharmacy costs. Similar
      results were observed in the Medicaid population. Conclusions: Baseline results
      suggest a prescribing preference for clobazam in severe LGS patients. Clobazam
      users had a reduction in seizure-related medical utilization and costs after
      clobazam initiation. The improvement in medical costs mostly offset the higher
      prescription costs following clobazam initiation.

PMID- 28740621
TI  - Direct cost analysis of the second year post-allogeneic hematopoietic stem cell
      transplantation in the Bone Marrow Transplant Centre of Tunisia.
AB  - Background: Hematopoietic stem cell transplantation (HSCT) is a medically
      complicated therapy with a long recovery time. In Tunisia, the National Health
      Insurance Fund (CNAM) covers only the first year post-transplantation, after
      which the costs are borne by the hospital. Objective: Describe complications that
      can occur during the second year post-allogeneic HSCT and calculate direct costs
      in different groups of patients. Methods: In this pharmacoeconomic study, medical
      records of the second year post-allogeneic HSCT were collected. Studied variables
      included frequent observed complications and medical and non-medical direct
      costs. Results: The average total direct cost in the population during the second
      year post-transplantation was $11,571, 97% of which represents direct medical
      costs Drugs accounted for the largest share (80%) of total direct costs,
      dominated by the cost of antifungals (52%) and antivirals (26%) drug .
      Cytomegalovirus status was seen in 9.3% of patients and was associated with a
      seven-fold increase in direct costs (p < 0.001).In patients who developed chronic
      GVHD, the average direct cost was three times higher than for those who did not
      (p = 0.032). Conclusion: Given the importance of direct costs in the post
      transplantation period a review of the hospital financing mechanism and a new
      convention with the CNAM is crucial..

PMID- 28740622
TI  - Drug pricing and reimbursement information management: processes and decision
      making in the global economy.
AB  - Background: Cost-containment initiatives are re-shaping the pharmaceutical
      business environment and affecting market access as well as pricing and
      reimbursement decisions. Effective price management procedures are too complex to
      accomplish manually. Prior to February 2013, price management within Astellas
      Pharma Europe Ltd was done manually using an Excel database. The system was
      labour intensive, slow to update, and prone to error. An innovative web-based
      pricing information management system was developed to address the shortcomings
      of the previous system. Development: A secure web-based system for submitting,
      reviewing and approving pricing requests was designed to: track all pricing
      applications and approval status; update approved pricing information
      automatically; provide fixed and customizable reports of pricing information;
      collect pricing and reimbursement rules from each country; validate pricing and
      reimbursement rules monthly. Several sequential phases of development emphasized
      planning, time schedules, target dates, budgets and implementation of the entire
      system. A test system was used to pilot the electronic (e)-pricing system with
      three affiliates (four users) in February 2013. Outcomes: The web-based system
      was introduced in March 2013, currently has about 227 active users globally and
      comprises more than 1000 presentations of 150 products. The overall benefits of
      switching from a manual to an e-pricing system were immediate and highly visible
      in terms of efficiency, transparency, reliability and compliance. Conclusions:
      The e-pricing system has improved the efficiency, reliability, compliance,
      transparency and ease of access to multinational drug pricing and approval
      information.

PMID- 28740623
TI  - Patient access to reimbursed biological disease-modifying antirheumatic drugs in
      the European region.
AB  - Background & Objectives: Biological disease-modifying antirheumatic drugs
      (bDMARDs) for the treatment of rheumatoid arthritis (RA) are not always
      accessible to all patients in accordance with international guidelines, partly
      owing to their high direct costs against a background of restricted healthcare
      budgets. This study compares the size of RA patient populations with access to
      reimbursed bDMARDs across 37 European countries, Russia, and Turkey, according to
      their treatment eligibility defined by European League Against Rheumatism (EULAR)
      recommendations and national reimbursement criteria. Methods: The size of the RA
      patient population eligible for bDMARD treatment was estimated in a population
      model using published RA epidemiological data and clinical criteria defined by
      2013 EULAR recommendations along with national reimbursement criteria defined in
      a survey of the 39 countries in November 2015. Results: According to EULAR
      recommendations, 32% of the total RA population in the European region is
      eligible for bDMARD treatment. However, only an average 59% of this EULAR
      eligible population remains eligible after applying national reimbursement
      criteria (from 86% in 'high access' to 13% in 'low-access' countries).
      Conclusion: Access to reimbursed bDMARDs remains unequal in the European region.
      As biosimilars of bDMARDs are introduced, changes in reimbursement criteria may
      increase access to bDMARDs and reduce this inequality.

PMID- 28740624
TI  - The effect of statins on the organs: similar or contradictory?
AB  - Hydroxy-Methyl-Glutaryl-CoA reductase (HMGCR) - the main enzyme of the
      cholesterol biosynthesis pathway - is mostly inhibited by statins in hepatocytes.
      In spite of the other tissues, liver utilizes cholesterol in different ways such
      as the synthesis of bile acids, excretion in to the intestine and synthesis of
      lipoproteins. Therefore, statins theoretically alter these pathways; although,
      there have not been such effects. In this review, we aim to show the roles of
      extra-hepatic tissues, in particular intestine, adipose and cutaneous tissues in
      providing the cholesterol after reduction of the whole body cholesterol content
      by statins.

PMID- 28740625
TI  - Pulmonary valve replacement in patients with corrected tetralogy of Fallot.
AB  - Introduction: Development of pulmonary insufficiency in patients with surgically
      corrected tetralogy of Fallot (TOF) may lead to severe right heart failure with
      serious consequences. We herein present our experience with pulmonary valve
      replacement (PVR) in these patients. Methods: From 2005-2013, 99 consecutive
      patients (71 males/28 females, mean age 38+/-8 years), underwent PVR after 7 to
      40 (mean 29 +/- 8) years from the initial correction. Seventy nine of the
      symptomatic patients presented in NYHA II, 14 in III and 2 in IV. All underwent
      PVR with a stented bioprosthetic valve, employing a beating heart technique with
      normothermic extracorporeal circulation support. Concomitant procedures included
      resection of aneurysmal outflow tract patches (n = 37), tricuspid valve
      annuloplasty (n = 36), augmentation of stenotic pulmonary arteries (n = 9), maze
      procedure (n = 2) and pulmonary artery stenting (n = 4). Results: There were 2
      perioperative deaths (2%). One patient developed sternal dehiscence requiring
      rewiring. Median ICU and hospital stay was 1 and 7 days respectively.
      Postoperative echocardiography at 6 and 12 months showed excellent bioprosthetic
      valve performance, significant decrease in size of the right cardiac chambers and
      reduction of tricuspid regurgitation (TR) in the majority of the patients. At
      mean follow-up of 3.6 +/- 2 years, all surviving patients remain in excellent
      clinical condition. Conclusion: Probability of reoperation for pulmonary
      insufficiency in patients with surgically corrected TOF increases with time and
      timely PVR by preventing the development of right heart failure is crucial for
      long-term survival. Current bioprosthetic valve technology in combination with
      the beating heart technique provides excellent immediate and short-term results.
      Further follow-up is necessary to evaluate long-term outcome.

PMID- 28740626
TI  - Fatty acids composition of aorta and saphenous vein tissues in patients with
      coronary artery diseases.
AB  - Introduction: Considering importance of fatty acids in developing coronary artery
      disease (CAD) and lack of information about saphenous vein which is commonly used
      as coronary arterial bypass, in this study we investigated differences in fatty
      acids composition between saphenous vein and aorta tissues in patients with CAD.
      Methods: Biopsy samples of aortic tissues and saphenous veins as well as blood
      samples were obtained form 42 patients with CAD. Fatty acids composition of the
      tissues was determined using gas chromatography and also serum lipid profile was
      evaluated by commercial kits. Results: Levels of palmitic acid (16:0) were
      significantly higher in aorta in compared with saphenous (P < 0.001). Also levels
      of most unsaturated fatty acids (16:1, 18:1n-9, 18:1t, 18:2t, 18:3 n-9 and 22:3n
      3) were statistically higher in saphenous tissue than aorta tissue (P < 0.05).
      Mean levels of linoleic acid (18:2 n-6) was higher in aorta tissue in comparison
      with saphenous tissue (P = 0.01). We observed positive correlations between serum
      levels of LDL-C with elaidic acid and linoleic acid levels in saphenous.
      Evaluation of aorta tissue fatty acids revealed that palmitoleic acid (16:1) had
      positive and arachidonic and linoleic acids had negative correlations with serum
      HDL-C levels. Conclusion: Our results revealed difference between fatty acids
      composition of aorta and saphenous vein tissues and existence of correlations
      between the fatty acids levels with serum lipid profile. The saphenous vein had
      higher poly-unsaturated fatty acids in compared to aorta tissue and thus this
      vein is not at risk of atherosclerosis and can be used as coronary arterial
      bypass.

PMID- 28740627
TI  - Correlation between severity of ultrasonographic nonalcoholic fatty liver disease
      and cardiometabolic risk among Filipino wellness patients.
AB  - Introduction: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition
      which is known to be related to factors that predispose to the development of
      coronary artery disease as well as development of metabolic syndrome. The study
      aimed to determine the association between ultrasound-based grading of hepatic
      steatosis with metabolic profile and estimated cardiovascular risk using the
      Framingham Risk Score (FRS). Methods: This was a cross-sectional study on 100
      Filipino patients without established cardiovascular disease who underwent a
      general wellness health evaluation. Cases with NAFLD diagnosed on the basis of
      ultrasound grading were analyzed. Comparison of demographics and metabolic
      parameters between grades of hepatic steatosis was performed using Kruskal Wallis
      test. FRS was used to assess cardiovascular risk with Spearman rank test for
      correlation with the degree of NAFLD. Results: Mean age was 47 +/- 9.6 years,
      with 70% males. Mean body mass index (BMI) was 28.7 +/- 5.1. Most patients had
      grade I NAFLD (53%), 34% were grade II, and 13% were grade III. BMI (P =0.034),
      liver enzymes (alanine aminotransferase [ALT], P = 0.001; aspartate
      aminotransferase [AST], P = 0.00), triglycerides (P = 0.047), and fasting blood
      sugar [FBS] (P = 0.049) were associated with fatty liver grade. No association
      was noted with total cholesterol (P = 0.569), high density lipoprotein (HDL) (P =
      0.220), and low density lipoprotein (LDL) (P = 0.792). Using the FRS 43% were
      stratified as low (<10% risk), 45% as intermediate (10%-20% risk) and 12% as high
      risk (>20% risk). Severity of fatty liver was directly correlated with the FRS
      (Spearman rank 0.741, P = 0.009). Conclusion: Ultrasound-based grading of the
      severity of NAFLD is associated with abnormalities in the metabolic profile of
      patients. The FRS is correlated with increasing severity of NAFLD based on
      ultrasound. These findings suggest that the presence of NAFLD may be a marker for
      the presence of increased cardiovascular risk and may help identify patients who
      may benefit from more aggressive therapies to prevent development of adverse
      cardiovascular events.

PMID- 28740628
TI  - Impact of high-fat diet and hypoxia on the serum levels of main vasoconstrictors
      in male rabbits.
AB  - Introduction: During atherosclerosis process, vasoconstriction phenomenon occurs
      which in turn leads to tissue hypoxia. A few studies have been performed on the
      combination of atherosclerosis and hypoxia as stressors that may accelerate
      secretion of constrictors. The aim of present study was to evaluate the effects
      of atherosclerosis and hypoxia on serum levels of main vasoconstrictors
      (epinephrine, norepinephrine and renin). Methods: In this interventional study,
      32 New Zealand white rabbits were randomly divided into four groups (n = 8):
      normal diet (control group), normal diet exposed to hypoxia (11%, 10 days), high
      fat diet (cholesterol-2%, 8 weeks), and high-fat diet with hypoxia. Later, serum
      levels of renin, epinephrine and norepinephrine were measured on second, 56th and
      66th days. Results: High-fat diet and hypoxia caused significant increase in
      epinephrine and norepinephrine concentrations on days 56 and 66 compared to the
      control group (P < 0.05). Also, renin showed significance increase in high-fat
      diet and high-fat diet+ hypoxia groups compared to the control group (P < 0.05).
      Conclusion: Both high-fat diet and hypoxia increase renin levels in male rabbits.
      Furthermore, the combination of high-fat diet and hypoxia immensely increases
      renin levels. Both hypoxia and combined of high-fat diet and hypoxia increase
      norepinephrine levels. However epinephrine is only increased in the combination
      of high-fat diet and hypoxia. So the presence of hypoxia in combination with high
      fat diet, cause accelerated and aggravated atherosclerosis.

PMID- 28740629
TI  - Comparison of coronary artery disease guidelines with extracted knowledge from
      data mining.
AB  - Introduction: Coronary artery disease (CAD) is one of the major causes of
      disability and death in the world. Accordingly utilizing from a national and
      update guideline in heart-related disease are essential. Finding interesting
      rules from CAD data and comparison with guidelines was the objectives of this
      study. Methods: In this study 1993 valid and completed records related to
      patients (from 2009 to 2014) who had suffered from CAD were recruited and
      analyzed. Total of 25 variable including a target variable (CAD) and 24 inputs or
      predictor variables were used for knowledge discovery. To perform comparison
      between extracted knowledge and well trusted guidelines, Canadian Cardiovascular
      Society (CCS) guideline and US National Institute of Health (NIH) guideline were
      selected. Results of valid datamining rules were compared with guidelines and
      then were ranked based on their importance. Results: The most significant factor
      influencing CAD was chest pain. Elderly males (age >54) have a high probability
      to be diagnosed with CAD. Diagnostic methods that are listed in guidelines were
      confirmed and ranked based on analyzing of local CAD patients data. Knowledge
      discovery revealed that blood test has more diagnostic value among other medical
      tests that were recommended in guidelines. Conclusion: Guidelines confirm the
      achieved results from data mining (DM) techniques and help to rank important risk
      factors based on national and local information. Evaluation of extracted rules
      determined new patterns for CAD patients.

PMID- 28740630
TI  - Safety and effect of high dose allopurinol in patients with severe left
      ventricular systolic dysfunction.
AB  - Introduction: Allopurinol used in the treatment of gout has been shown to improve
      the vascular endothelial dysfunction and reduce the dysfunction of the failing
      heart. This study was done to evaluate the effect and safety of allopurinol in
      non-hyperuricemic patients with chronic severe left ventricular (LV) dysfunction.
      Methods: In this study, 35 consecutive cases of non-hyperuricemic patients with
      chronic heart failure who had severe LV systolic dysfunction (ejection fraction
      of less than 35%) and were on optimal guideline directed medical therapies for at
      least 3 months were included. Allopurinol was administered with the dose of 300
      mg po daily for 1 week and then it was up-titrated to a dose of 600 mg po daily
      for 3 months. Six minute walk test, strain imaging, laboratory testing were done
      for every patient at baseline and after 3 months treatment with allopurinol.
      Results: In this study 30 heart failure (HF) patients with a mean age of 49.3 +/-
      14.4 years old were evaluated. No adverse effects were reported except for one
      case of skin rash after 4 days treatment which was excluded from the study. Study
      showed significant improvement of six minute walk test of the patients from 384.5
      +/- 81.5 meters to 402.8 +/- 89.6 meters and the global longitudinal peak strain
      (P < 0.001). There was also significant decrease in the level of erythrocyte
      sedimentation rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) after
      3 months. Conclusion: Allopurinol could be of benefit in non-hyperuricemic
      patients with severe LV systolic dysfunction without significant adverse effects.
      Randomized clinical trials are needed in future to confirm the results.

PMID- 28740631
TI  - Increased risk of coronary perforation during percutaneous intervention of
      myocardial bridge: What histopathology says.
AB  - Introduction: Myocardial bridge (MB) is a segment of a major epicardial coronary
      artery that goes intramurally under a bridge of overlying myocardium.
      Complications have been reported during or after stent implantation particularly
      coronary perforation. The aim of this study was to determine histological
      differences between proximal left anterior descending artery (LAD) and the
      tunneled segment that may have a possible role in increased risk of coronary
      artery perforation during percutaneous coronary intervention. Methods: Twenty
      specimens of MB were obtained from dissection of 45 cadavers. Sections were
      stained using hematoxylin and eosin (H&E), and trichrome methods. The proximal
      section and the tunneled artery were compared with a normal sample in terms of
      the characteristics of a muscle artery. Results: The findings of this study
      showed an MB prevalence of 51%, as 23 out of the 45 examined cadavers were
      discovered to be afflicted by the MB. The intima layer in the suffering artery
      had gone through significant hypertrophy, while it had remained thin in the
      tunneled artery section. The epithelial cells under the bridge were spindle
      shaped, while they were polygonal in the proximal section. In the myocardium the
      nuclei of the muscle fibers in the MB section were smaller than the normal
      section. Adventitial layer was almost normal. Conclusion: The histopathological
      differences between MB and proximal part of vessel combined with small vessel
      diameter in the tunneled segment can explain the high incidence of the LAD
      rupture and perforation in the section under the bridge.

PMID- 28740632
TI  - Psychological effects on patient's relatives regarding their presence during
      resuscitation.
AB  - Introduction: Presence of family and patients' relatives throughout resuscitation
      procedure is one of the most challenging concerns. Methods: In an interventional
      (quasi-experimental) study that was conducted during a 6 months period, the
      patients' relatives were randomly divided into two groups of intervention (the
      relatives who were eager to be present throughout the resuscitation procedure-
      under the family protection protocol, all of the procedure steps were explained
      to the relatives by an expert nurse who was not involved in the resuscitation
      procedure and control group (those who were not invited routinely to be present
      throughout the resuscitation procedure. However, if the control group were eager
      to be present, they were allowed to observe the procedure (these people were not
      supported by the protocol). After 90 days, subjects were contacted through
      telephone and filled standard questionnaires (Hospital Anxiety and Depression
      Scale [HADS]) and Impact of Event Scale (IES) were completed for all subjects.
      These questionnaires focus on anxiety, depression and post-traumatic stress
      disorder (PTSD). The obtained data were analyzed. Results: One hundred thirty
      three relatives were divided into two groups of control (59 subjects) and
      intervention (74 people). No significant difference was observed between two
      groups regarding demographic features. The evaluation after 90 days revealed
      depression, anxiety disorders and PTSD to be significantly more prevalent in
      control group than the intervention group (P < 0.0001 ). Conclusion: Emotional
      and psychological support and intervention on the patients' relatives are
      efficient and can prevent the emergence of psychological disorders.

PMID- 28740633
TI  - Papillary fibroelastoma arising from the coumadin ridge.
AB  - Cardiac papillary fibroelastomas (CPF) are rare cardiac tumors, mostly found on
      the valvular surfaces in the heart. These tumors are frond like in nature and are
      benign, intracardiac masses, rarely causing any hemodynamic disturbances.
      However, excision of these masses is indicated due to their propensity to
      embolize. We present a case report of the tumor found on the coumadin ridge,
      causing transient ischemic attacks in a patient. We performed complete excision
      of the tumor via median sternotomy on cardiopulmonary bypass support with cardiac
      arrest. The diagnosis was confirmed by histological examination. The patient had
      an uneventful postoperative course and was discharghed on postoperative day 4.
      She has had complete resolution of her symptoms post excision. The diagnosis of
      the mass was confirmed on histological examination.

PMID- 28740634
TI  - Human papillomavirus and gastrointestinal cancer in Iranian population: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Gastrointestinal (GI) malignancies are the most common cancers and
      account for nearly half of all cancer-related deaths in Iran. There was a strong
      association between human papillomavirus (HPV) infection and urogenital cancers,
      in particular the cervix. However, there is no clear causal relationship in all
      types of cancers, including gastrointestinal cancers. Therefore, the present
      study as a systematic review and meta-analysis was designed to evaluate the
      prevalence and relation of HPV in GI cancers. METHODS: This systematic review and
      meta-analysis study assess the prevalence of human papillomavirus in GI cancers
      in Iran. Data were collected by searching electronic databases, including PubMed,
      Google Scholar, Scopus, SID and Iranmedex by English and Persian key words up to
      August 2016. Key words included: Human Papillomavirus, HPV, Cancer, Neoplasm,
      Carcinoma, Esophageal, colorectal, Gastrointestinal and Iran articles were
      entered in the EndNote software and duplicate papers were excluded. Data were
      extracted and analyzed by comprehensive meta-analysis software, Version 2
      (CMA.V2) and random effects model. RESULTS: Finally, we included 17 studies in
      this meta-analysis. The prevalence of HPV in Iranian patients with GI cancers was
      16.4% (CI95%: 10.4-24.9). Considering all HPV types, the odds ratio of GI cancers
      in positive patients was 3.03 (CI95%: 1.42-6.45) while in patients with HPV-16
      was 3.62 (CI: 1.43-4.82). CONCLUSION: The results show a strong relationship
      between HPV infection especially high-risk HPV type 16 and GI cancers in Iranian
      population.

PMID- 28740635
TI  - Supratentorial acute subdural haematoma during microvascular decompression
      surgery: report of three cases.
AB  - Supratentoiral haemorrhage during posterior fossa surgery is very rare. Authors
      report three cases of acute subdural haematoma occurred during microvascular
      decompression (MVD). Bleeding was observed in the suboccipital surgical area
      during operation but the origin of the bleeding was not confirmed
      intraoperatively in all cases. Decompression procedure was completed and
      immediate postoperative computed tomography revealed supratentorial subdural
      haematoma. This complication was observed during MVD in healthy young patients
      with hemifacial spasm in our cases. Flexion of the head with reduction of
      cerebrospinal fluid may have induced rotational movement of the cerebrum
      resulting in rupture of bridging veins, but no definitive mechanism that fulfils
      the clinical characteristics was clearly determined.

PMID- 28740636
TI  - Long-term use of benzodiazepines in older patients in Germany: a retrospective
      analysis.
AB  - BACKGROUND: The purpose of this study was to analyze the prevalence of long-term
      benzodiazepine use in older adults treated in general and neuropsychiatric
      practices in Germany. METHODS: This study included 32,182 patients over the age
      of 65 years who received benzodiazepine prescriptions for the first time between
      January 2010 and December 2014 in general and neuropsychiatric practices in
      Germany. Follow up lasted until July 2016. The main outcome measure was the
      proportion of patients treated with benzodiazepines for >6 months. RESULTS: The
      proportion of patients with benzodiazepine therapy for >6 months increased with
      age (65-70 years: 12.3%; 71-80 years: 15.5%; 81-90 years: 23.7%; >90 years:
      31.6%) but did not differ significantly between men (15.5%) and women (17.1%).
      The proportion of patients who received benzodiazepines for >6 months was higher
      among those with sleep disorders (21.1%), depression (20.8%) and dementia (32.1%)
      than among those with anxiety (15.5%). By contrast, this proportion was lower
      among people diagnosed with adjustment disorders (7.7%) and back pain (3.8%).
      CONCLUSION: Overall, long-term use of benzodiazepines is common in older people,
      particularly in patients over the age of 80 and in those diagnosed with dementia,
      sleep disorders, or depression.

PMID- 28740637
TI  - Antipsychotic-induced hyperprolactinemia in Tourette syndrome.
AB  - For many years, Tourette syndrome (TS) was considered to be a rare disorder, but
      tics and TS are now recognized as fairly common childhood-onset conditions.
      Children and adolescents with TS are frequently treated with antipsychotics,
      either as monotherapy or in combination with psychostimulants, melatonin and
      selective serotonin reuptake inhibitors (SSRIs). Antipsychotics are most often
      used in schizophrenia and related psychotic disorders, and in these conditions
      hyperprolactinemia is one of the most common adverse effects associated with
      antipsychotics, occurring in 40-50% of patients. We describe two patients with TS
      who experienced antipsychotic-induced hyperprolactinemia. Treatment options
      generally consist of dose reduction or switching from typical to atypical
      antipsychotics. However, diminishing dosages can lead to exacerbations of tics.
      Also, not all atypical antipsychotics have the same pharmacologic properties
      required to normalize prolactin levels. The choice of treatment may also be
      affected by the patient's age and sex. These factors are discussed in relation to
      these cases, and illustrated by the results of therapeutic interventions over the
      years.

PMID- 28740638
TI  - Nutritional physiology and ecology of wildlife in a changing world.
AB  - Over the last century, humans have modified landscapes, generated pollution and
      provided opportunities for exotic species to invade areas where they did not
      evolve. In addition, humans now interact with animals in a growing number of ways
      (e.g. ecotourism). As a result, the quality (i.e. nutrient composition) and
      quantity (i.e. food abundance) of dietary items consumed by wildlife have, in
      many cases, changed. We present representative examples of the extent to which
      vertebrate foraging behaviour, food availability (quantity and quality) and
      digestive physiology have been modified due to human-induced environmental
      changes and human activities. We find that these effects can be quite extensive,
      especially as a result of pollution and human-provisioned food sources (despite
      good intentions). We also discuss the role of nutrition in conservation
      practices, from the perspective of both in situ and ex situ conservation. Though
      we find that the changes in the nutritional ecology and physiology of wildlife
      due to human alterations are typically negative and largely involve impacts on
      foraging behaviour and food availability, the extent to which these will affect
      the fitness of organisms and result in evolutionary changes is not clearly
      understood, and requires further investigation.

PMID- 28740639
TI  - RGD peptide and graphene oxide co-functionalized PLGA nanofiber scaffolds for
      vascular tissue engineering.
AB  - In recent years, much research has been suggested and examined for the
      development of tissue engineering scaffolds to promote cellular behaviors. In our
      study, RGD peptide and graphene oxide (GO) co-functionalized poly(lactide-co
      glycolide, PLGA) (RGD-GO-PLGA) nanofiber mats were fabricated via
      electrospinning, and their physicochemical and thermal properties were
      characterized to explore their potential as biofunctional scaffolds for vascular
      tissue engineering. Scanning electron microscopy images revealed that the RGD-GO
      PLGA nanofiber mats were readily fabricated and composed of random-oriented
      electrospun nanofibers with average diameter of 558 nm. The successful co
      functionalization of RGD peptide and GO into the PLGA nanofibers was confirmed by
      Fourier-transform infrared spectroscopic analysis. Moreover, the surface
      hydrophilicity of the nanofiber mats was markedly increased by co-functionalizing
      with RGD peptide and GO. It was found that the mats were thermally stable under
      the cell culture condition. Furthermore, the initial attachment and proliferation
      of primarily cultured vascular smooth muscle cells (VSMCs) on the RGD-GO-PLGA
      nanofiber mats were evaluated. It was revealed that the RGD-GO-PLGA nanofiber
      mats can effectively promote the growth of VSMCs. In conclusion, our findings
      suggest that the RGD-GO-PLGA nanofiber mats can be promising candidates for
      tissue engineering scaffolds effective for the regeneration of vascular smooth
      muscle.

PMID- 28740640
TI  - Effects of early administration of acetazolamide on the duration of mechanical
      ventilation in patients with chronic obstructive pulmonary disease: still far
      from the truth?

PMID- 28740641
TI  - Lung ultrasound: a new basic, easy, multifunction imaging diagnostic tool in
      children undergoing pediatric cardiac surgery.

PMID- 28740642
TI  - Does temperature management improve outcome in patients resuscitated from a non
      shockable rhythm?

PMID- 28740643
TI  - Optical coherence tomography- vs. intravascular ultrasound-guided percutaneous
      coronary intervention.

PMID- 28740644
TI  - The hemodynamic impact of acute nasal continuous positive airway pressure
      treatment in hypertrophic cardiomyopathy: is it safe?

PMID- 28740645
TI  - Immunosuppression after lung transplantation: the search for the holy grail
      continues.

PMID- 28740646
TI  - What is extracorporeal cardiopulmonary resuscitation?

PMID- 28740647
TI  - Hypercapnia during acute respiratory distress syndrome: the tree that hides the
      forest!

PMID- 28740648
TI  - Another disappointing result, but how good is it?

PMID- 28740649
TI  - Novel centrifugal pump for heart failure patients: initial success and future
      challenges.

PMID- 28740650
TI  - Rapid adoption of transcatheter aortic valve replacement in intermediate- and
      high-risk patients to treat severe aortic valve stenosis.

PMID- 28740651
TI  - Renin angiotensin system inhibitors: a panacea for heart disease?

PMID- 28740652
TI  - No prophylaxis is non-inferior and cost-saving to prophylactic intravenous
      hydration in preventing contrast-induced nephropathy on requiring iodinated
      contrast material administration.

PMID- 28740653
TI  - Diagnosing and treating contrast-induced acute kidney injury in 2017.

PMID- 28740654
TI  - A novel therapeutic approach for esophageal squamous cell carcinoma: suppressor
      of cytokine signaling-1 gene therapy.

PMID- 28740655
TI  - Editorial on role of p53 in esophageal cancer from a meta-analysis of 16 studies
      by Fisher et al.

PMID- 28740656
TI  - Biomarkers in the era of individualized medicine.

PMID- 28740657
TI  - The esophagogastric junctional adenocarcinoma an increasing disease.

PMID- 28740658
TI  - SIRS, qSOFA, and organ failure for assessing sepsis at the emergency department.

PMID- 28740659
TI  - Shooting for the bull's eye in septic shock.

PMID- 28740660
TI  - Brain response to sleep-related attentional bias in patients with chronic
      insomnia.

PMID- 28740662
TI  - Treatment for sternoclavicular joint infections: a multi-institutional study.
AB  - BACKGROUND: Sternoclavicular joint (SCJ) infections are rare and difficult to
      manage. Surgery is necessary for treatment. METHODS: A retrospective chart review
      of the university hospital and Veterans Administration (VA) hospitals of all
      patients treated for SCJ infections since 2001 was conducted. Fifteen [15]
      patients were identified and evaluated for the types of infections, risk factors,
      treatments and survival. RESULTS: All 15 patients were symptomatic including:
      pain [13], erythema [9], purulent drainage [3], fever greater than 38.3  degrees
      C [2], and leukocytosis [9]. The associated medical problems included: diabetes
      mellitus (DM), hypertension (HTN) and renal failure. All patients underwent
      intraoperative joint resection. Sixty-seven percent (67%) of intraoperative wound
      cultures grew staphylococcus aureus. Fourteen patients were discharged on
      intravenous antibiotics. The follow-up ranged between 1 week-11 months. Thirteen
      patients are currently alive without infection. Two patients died: 1 of sepsis
      and 1 of unknown causes after discharge. CONCLUSIONS: Symptomatic SCJ infections
      require surgical intervention. The most common organism was staphylococcus
      aureus.

PMID- 28740663
TI  - Evaluation of platelet lymphocyte ratio and 90-day mortality in patients with
      acute exacerbation of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD)
      have high mortality and health care costs. The platelet to lymphocyte ratio (PLR)
      is a marker of inflammation and has been reported to be elevated in patients with
      AECOPD compared to stable state. In this study, we sought to evaluate the
      association of the PLR in patients with AECOPD with 90-day mortality. METHODS: We
      conducted a retrospective cohort study of patients admitted to our institution
      with a primary diagnosis of AECOPD between January 2014 and July 2014. Blood test
      results on admission were recorded. The primary outcomes were 90-day mortality.
      RESULTS: One hundred and eighty-one AECOPD patients were considered for the
      study. Death had occurred in 16 (9%) patients within 90 days of hospital
      discharge. Univariable analysis identified age, haemoglobin, neutrophil count,
      and urea level, neutrophil lymphocyte ratio (NLR) and PLR as being associated
      with increased 90-day mortality. Multivariable logistic regression analysis
      variables demonstrated that only PLR (P=0.03) was significantly associated with
      death at 90 days. Receiver operator characteristic analysis identified PLR >=235
      had a sensitivity of 63% and specificity of 74% in predicting 90-day mortality.
      PLR was >=235 was also associated with worse survival (days) [mean +/- standard
      deviation (SD): PLR >=235 vs. PLR <235: 512+/-358 vs. 626+/-346, P=0.004].
      CONCLUSIONS: A PLR >=235 was significantly associated with 90-day mortality,
      which may provide prognostic guidance to clinicians.

PMID- 28740661
TI  - South African guideline for the management of community-acquired pneumonia in
      adults.

PMID- 28740664
TI  - Development of a novel ex vivo porcine laparoscopic Heller myotomy and Nissen
      fundoplication training model (Toronto lap-Nissen simulator).
AB  - BACKGROUND: Surgical trainees are required to develop competency in a variety of
      laparoscopic operations. Developing laparoscopic technical skills can be
      difficult as there has been a decrease in the number of procedures performed.
      This study aims to develop an inexpensive and anatomically relevant model for
      training in laparoscopic foregut procedures. METHODS: An ex vivo, anatomic model
      of the human upper abdomen was developed using intact porcine esophagus, stomach,
      diaphragm and spleen. The Toronto lap-Nissen simulator was contained in a
      laparoscopic box-trainer and included an arch system to simulate the normal
      radial shape and tension of the diaphragm. We integrated the use of this training
      model as a part of our laparoscopic skills laboratory-training curriculum.
      Afterwards, we surveyed trainees to evaluate the observed benefit of the learning
      session. RESULTS: Twenty-five trainees and five faculty members completed a
      survey regarding the use of this model. Among the trainees, only 4 (16%) had
      experience with laparoscopic Heller myotomy and Nissen fundoplication. They
      reported that practicing with the model was a valuable use of their limited time,
      repeating the exercise would be of additional benefit, and that the exercise
      improved their ability to perform or assist in an actual case in the operating
      room. Significant improvements were found in the following subjective measures
      comparing pre- vs. post-training: (I) knowledge level (5.6 vs. 8.0, P<0.001);
      (II) comfort level in assisting (6.3 vs. 7.6, P<0.001); and (III) comfort level
      in performing as the primary surgeon (4.9 vs. 7.1, P<0.001). The trainees and
      faculty members agreed that this model was of adequate fidelity and was a
      representative simulation of actual human anatomy. CONCLUSIONS: We developed an
      easily reproducible training model for laparoscopic procedures. This simulator
      reproduces human anatomy and increases the trainees' comfort level in performing
      and assisting with myotomy and fundoplication.

PMID- 28740665
TI  - Decrease in performance status after lobectomy mean poor prognosis in elderly
      lung cancer patients.
AB  - BACKGROUND: Surgery remains the best treatment for obtaining cure in patients
      with resectable lung cancer, regardless of age. In elderly patients, however, the
      presumed fear of decreased performance status (PS) after lobectomy has resulted
      in the delivery of sub-optimal cancer surgery. Surgical decision making for such
      patients would become easier if post-lobectomy survival benefits and changes in
      PS were well defined. METHODS: We reviewed patients aged 75 years or older who
      received lobectomy for non-small cell lung cancer (NSCLC) at our hospital between
      January 2004 and December 2014. Eastern Cooperative Oncology Group PS was
      preoperatively and postoperatively assessed in 137 patients. Patients were
      classified into 2 groups based on the change in PS: in Group 1, postoperative and
      preoperative PS were the same; in group 2, postoperative PS was less than
      preoperative PS. We compared the characteristics of patients in groups 1 and 2.
      RESULTS: Overall 5-year survival was 47.4% in group 1 and 0% in group 2
      (P<0.001). History of cardiac ischemia (P=0.001) and squamous cell carcinoma
      (P=0.015) were identified as significant predictors of reduced postoperative PS.
      CONCLUSIONS: Our results show that maintenance of PS after lobectomy is expected
      to be associated with a good prognosis. However, reduction of PS after lobectomy
      indicates an extremely poor prognosis in elderly patients with lung cancer.
      History of cardiac ischemia and squamous cell carcinoma are possible risk factors
      for decreasing PS. Thus, careful patient evaluation and selection are needed when
      deciding whether to use lobectomy in clinical practice.

PMID- 28740666
TI  - The value of positive lymph nodes ratio combined with negative lymph node count
      in prediction of breast cancer survival.
AB  - BACKGROUND: Positive lymph node ratio (LNR), defined as ratio of positive lymph
      nodes to all lymph nodes removed, is a powerful prognostic factor in invasive
      breast cancer. Here we focused on the impact of negative lymph node (NLN) count
      on the prediction of value of LNR in breast cancer survival. METHODS: Of 929
      invasive breast cancer patients were enrolled in our retrospective study. We use
      Kaplan-Meier to calculate the 5-year overall survival (OS) according to different
      clinicopathologic parameters. The prediction value of NLN count and LNR in OS was
      examined. RESULTS: The optimal cutoff of NLN count was designated as 9. Five-year
      OS was 77.0% and 95.0% in patients with NLN of 0-9 and >=10, respectively
      (P<0.001). Among 204 patients who had 0-9 NLN, 25 patients with LNR 0-20.0% had 5
      year OS of 95.7%, 104 patients with LNR 20.1-65.0% had 5-year OS of 83.4%, and 75
      patients with LNR 65.1-100.0% had 5-year OS of 61.7% (P<0.001); Among 725
      patients who had NLN >=10, 650 patients with LNR 0-20.0% had 5-year OS of 96.1%,
      68 patients with LNR 20.1-65.0% had 5-year OS of 86.8%, and 7 patients with LNR
      65.1-100% had 5-year OS of 71.4% (P<0.001). CONCLUSIONS: High NLN count is
      associated with improved survival in invasive breast cancer patients. Combining
      NLN count with LNR could be considered as an alternative to LNR alone in
      prediction of postoperative breast cancer survival.

PMID- 28740667
TI  - Discordance of physician clinical judgment vs. pneumonia severity index (PSI)
      score to admit patients with low risk community-acquired pneumonia: a prospective
      multicenter study.
AB  - BACKGROUND: The relationship between clinical judgment and the pneumonia severity
      index (PSI) score in deciding the site of care for patients with community
      acquired pneumonia (CAP) has not been well investigated. The objective of the
      study was to determine the clinical factors that influence decision-making to
      hospitalize low-risk patients (PSI <=2) with CAP. METHODS: An observational,
      prospective, multicenter study of consecutive CAP patients was performed at five
      hospitals in Spain. Patients admitted with CAP and a PSI <=2 were identified.
      Admitting physicians completed a patient-specific survey to identify the clinical
      factors influencing the decision to admit a patient. The reason for admission was
      categorized into 1 of 6 categories. We also assessed whether the reason for
      admission was associated with poorer clinical outcomes [intensive care unit (ICU)
      admission, 30-day mortality or readmission]. RESULTS: One hundred and fifty-five
      hospitalized patients were enrolled. Two or more reasons for admission were seen
      in 94 patients (60.6%), including abnormal clinical test results (60%), signs of
      clinical deterioration (43.2%), comorbid conditions (28.4%), psychosocial factors
      (28.4%), suspected H1N1 pneumonia (20.6%), and recent visit to the emergency
      department (ED) in the past 2 weeks (7.7%). Signs of clinical deterioration and
      abnormal clinical test results were associated with poorer clinical outcomes
      (P<0.005). CONCLUSIONS: Low-risk patients with CAP and a PSI <=2 are admitted to
      the hospital for multiple reasons. Abnormal clinical test results and signs of
      clinical deterioration are two specific reasons for admission that are associated
      with poorer clinical outcomes in low risk CAP patients.

PMID- 28740668
TI  - Socioeconomic impact of asthma, chronic obstructive pulmonary disease and asthma
      COPD overlap syndrome.
AB  - BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome
      (ACOS) is defined as having both features of asthma and COPD, which are airway
      hyper-responsiveness and incompletely reversible airway obstruction. However,
      socioeconomic impact of ACOS have not been well appreciated. METHODS: Adults with
      available wheezing history and acceptable spirometry were selected from the
      fourth Korean National Health and Nutrition Examination Survey (KNHANES IV) in
      2007-2009. Their data were merged with the Korean National Health Insurance claim
      data. 'Asthma group' was defined as having self-reported wheezing history and
      FEV1/FVC >=0.7, 'COPD group' was defined as having FEV1/FVC <0.7 and no wheezing,
      'ACOS group' was defined as having both wheezing and FEV1/FVC <0.7, and 'no
      airway disease (NAD) group' was defined as having no wheezing and FEV1/FVC >=0.7.
      RESULTS: Among a total of 11,656 subjects, ACOS comprise 2.2%; COPD, 8.4%;
      asthma, 5.8% and NAD, 83.6%. Total length of healthcare utilization and medical
      costs of ACOS group was the top among four groups (P<0.001), though inpatient
      medical cost was the highest in COPD group (P=0.025). Multiple linear regression
      analyses showed that ACOS group (beta=12.63, P<0.001) and asthma group
      (beta=6.14, P<0.001) were significantly associated with longer duration of
      healthcare utilization and ACOS group (beta=350,475.88, P=0.008) and asthma group
      (beta=386,876.81, P<0.001) were associated with higher medical costs.
      CONCLUSIONS: This study demonstrated that ACOS independently influences
      healthcare utilization after adjusting several factors. In order to utilize
      limited medical resources efficiently, it may be necessary to find and manage
      ACOS patients.

PMID- 28740669
TI  - Impact of thoracic surgery on esophageal motor function-Evaluation by high
      resolution manometry.
AB  - BACKGROUND: Alteration of esophageal function is a potential risk factor for
      postoperative complications in thoracic surgery. This prospective study
      investigates esophageal motility and function during and after thoracic
      procedures via high resolution manometry (HRM) and impedance technology with
      spatiotemporal representation of pressure data. METHODS: Twelve consecutive
      patients eligible for elective thoracic surgery underwent preoperative and
      postoperative (48 hours and 7 days) esophageal HRM. Swallowing acts were carried
      out with 5 mL of water, 10 mL of water and 1 cm3 bread in physiological posture
      to evaluate distal contraction integral (DCI). Length and location of contractile
      integrity breaks were measured by investigators blinded to the form of surgical
      intervention. The impact of surgical procedures on esophageal motility was
      quantified according to current Chicago Classification (CC) criteria. Pre-, intra
      and postoperative 24-hour multi-channel impedance pH-metry (MII-pH) was
      performed to further analyze gastroesophageal reflux patterns. RESULTS: All
      patients were investigated 48 hours prior to and 7 days after thoracic
      procedures, with a total of n=675 swallowing acts being included in our study.
      Increased motility patterns of the tubular esophagus occurred temporally 48 hours
      postoperatively. DCI 48 hours after surgery increased significantly (5 mL,
      P=0.049; solid, P=0.014) and returned to baseline values after seven days (5 mL,
      P=0.039; solid, P=0.039). Break length was significantly reduced 48 hours
      postoperatively, especially in the proximal esophageal segment (transition zone).
      Follow-up measurements after another week were comparable to preoperative
      baseline findings. The perioperative MII-pH measurement showed numerous artifacts
      caused by intubation and ventilation during surgery also with increasing short
      and frequent acidic reflux episodes. CONCLUSIONS: Thoracic procedures cause a
      transient modulation of esophageal peristalsis with postoperative increased
      contractility of the tubular esophagus, presumably without affecting
      intraesophageal reflex arcs. Although limited by the number of patients, we can
      conclude on our data that postoperative esophageal hypomotility is unlikely to
      promote secondary pulmonary complications.

PMID- 28740670
TI  - Analysis of the risk factors of postoperative cardiopulmonary complications and
      ability to predicate the risk in patients after lung cancer surgery.
AB  - BACKGROUND: Postoperative cardiopulmonary complications might be fatal for
      patients with lung cancer after surgery. The aim of this study was to identify
      the risk factors of postoperative cardiopulmonary complications in lung cancer
      patients and get a fitting formula for predicting incidences of cardiopulmonary
      complications. METHODS: We conducted a retrospective analysis of 653 patients
      with a diagnosis of lung cancer who underwent a surgery in the Tianjin Medical
      University Cancer Institute and Hospital (Tianjin, China) from January to
      December 2014. All patients received lung cancer surgeries. Clinical data was
      collected for the analysis of the influence factors of cardiopulmonary
      complication after lung cancer surgeries. The medical statistical analysis
      program R was used to calculate cardiopulmonary complication probability of
      classification of quantitative results. RESULTS: Our work showed that ages,
      lymphocyte count, smoking history, chronic bronchitis history, operation mode and
      extubation time were significantly associated with lung infection both in
      univariate and multivariate survival analysis. And ages, smoking history,
      arrhythmia of electrocardiogram and operation mode were significantly associated
      with postoperative arrhythmia both in univariate and multivariate survival
      analysis. Multiple linear regressions were generated with risk factors by program
      R software. Finally, we got a fitting formula for predicting cardiopulmonary
      complications. Risk score for each patient could be obtained by this formula.
      CONCLUSIONS: The incidences of pulmonary infection and arrhythmia were high for
      patients who underwent lung cancer surgery. It is important to discriminate risk
      factors for each patient for reducing the risk of heart and lung complications.
      Preoperative quantitative evaluation of cardiopulmonary complication after
      operation is beneficial to the risk control.

PMID- 28740671
TI  - Decreased Wnt4 expression inhibits thymoma development through downregulation of
      FoxN1.
AB  - BACKGROUND: The Wnt signaling pathway controls the development of thymic
      epithelial cells by regulating the expression of FoxN1. Thymoma is a type of
      malignant tumor arising from the thymic epithelial cells. To determine whether
      Wnt4 and FoxN1 are involved in the pathogenesis of thymoma, this study determined
      the mRNA and protein levels of Wnt4 and Foxn1 in thymoma, and analyzed the effect
      of thymoma cell apoptosis and tumor growth in nude mice after Wnt4 and FoxN1
      downregulation. METHODS: Wnt4 and FoxN1 mRNA and protein levels in thymoma
      tissues were analyzed by RT-qPCR and immunohistochemistry, respectively. Thymoma
      cells were cultured and transfected with siRNA targeting the Wnt4, JNK, and FoxN1
      genes. Apoptosis of thymoma cells were analyzed after Wnt4 and FoxN1
      downregulation. In addition, thymoma cells were inoculated into nude mice and
      tumor growth was analyzed. RESULTS: The rates of expression of Wnt4 and FoxN1
      protein were 64.3% and 58.9%, while the levels of mRNA expression were 2.56+/
      0.04 and 1.83+/-0.11, respectively. With increasing malignancy of thymoma, the
      rates of positivity for Wnt4 and FoxN1 mRNA and protein expression gradually
      increased. Upon interfering with Wnt4, JNK, and FoxN1 gene expression by using
      siRNA technology, the inhibition rates were 56.7%, 72.6%, and 63.2%,
      respectively. The expression of FoxN1 mRNA and protein was decreased after Wnt4
      and JNK downregulation. After downregulation of Wnt4 and FoxN1 gene expression,
      the apoptosis rate of thymoma cells increased and the tumor volume decreased in
      nude mice. CONCLUSIONS: High expression of Wnt4 and FoxN1 may play an important
      role in the generation and development of thymoma. The FoxN1 gene produced a
      marked downstream effect through the regulation of Wnt4. Determining the
      positivity for both Wnt4 and FoxN1 can help us to evaluate the level of
      malignancy of thymoma.

PMID- 28740672
TI  - Effectiveness of perioperative pulmonary rehabilitation in thoracic surgery.
AB  - BACKGROUND: Functional condition is crucial for operability of patients with lung
      cancer and/or chronic respiratory diseases. The aim of the study was to measure
      changes of functional and quality of life parameters in terms of the
      effectiveness of perioperative pulmonary rehabilitation (PR). METHODS: A total of
      208 COPD patients (age: 63+/-9 years, man/woman: 114/94, FEV1: 62+/-14%pred)
      participated in a perioperative PR program. The indication was primary lung
      cancer in 72% of the patients. The 68 patients participated in preoperative (PRE)
      rehabilitation, 72 in a pre- and postoperative rehabilitation (PPO) and 68
      patients only in postoperative rehabilitation (POS). PR program included
      respiratory training techniques, individualized training and smoking cessation.
      Lung function tests, 6 minutes walking distance (6MWD) were measured before and
      after the rehabilitation. Quality of life tests [COPD Assessment Test (CAT) and
      Modified Medical Research Council Dyspnoea Scale (mMRC)] were evaluated as well.
      RESULTS: There was a significant improvement in FEV1 (PRE: 64+/-16 vs. 67+/
      16%pred; PPO: 60+/-13 vs. 66+/-13%pred before the operation, 48+/-13 vs. 52+/
      13%pred after the operation; POS: 56+/-16 vs. 61+/-14%pred, P<0.05) and 6MWD
      (PRE: 403+/-87 vs. 452+/-86 m; PPO: 388+/-86 vs. 439+/-83 m before, 337+/-111 vs.
      397+/-105 m after the operation; POS: 362+/-89 vs. 434+/-94 m, P<0 0001).
      Significant improvement was detected in FVC, grip strength, mMRC and CAT
      questionnaires as an effectiveness of PR, also. Average intensive care duration
      was 3.8+/-5.2 days with vs. 3.1+/-3.6 without preoperative PR. CONCLUSIONS:
      Improvements in exercise capacity and quality of life were seen following PR both
      before and after thoracic surgery.

PMID- 28740673
TI  - Clinical and pathological aspects of microscopic thymoma with myasthenia gravis
      and review of published reports.
AB  - BACKGROUND: Microscopic thymomas, defined as epithelial proliferations smaller
      than 1 mm in diameter, characteristically occur in patients with myasthenia
      gravis without macroscopic thymic epithelial tumors. However, some clinical and
      pathological aspects of this entity are still unclear. METHODS: This
      retrospective study includes five consecutive patients who had undergone extended
      thymectomy for myasthenia gravis at our institution from April 2007 to March 2016
      and in whom microscopic thymomas were diagnosed by histopathological examination
      of the resected specimens. During the same period, we performed 32 extended
      transsternal thymothymectomies/thymectomies in patients with myasthenia gravis,
      including the above five cases. We here review 18 cases of microscopic thymoma,
      including our five cases and 13 previously reported cases. RESULTS: The incidence
      of previously undiagnosed microscopic thymoma in patients undergoing thymectomy
      for myasthenia gravis in our institution is 15.2%. Serum preoperative anti
      acetylcholine receptor antibody (anti-AchR Ab) titers were abnormally high in all
      of our five cases h (74.4+/-53.3 nmol/L) and decreased significantly after
      surgery (11.7+/-13.5 nmol/L, P=0.037). We divided our cases into the following
      three groups: microscopic thymoma group (Group M), thymoma group (Group T) and
      non-thymic tumor group (Group N). The mean preoperative anti-AchR Ab titers of
      these groups were 74.4, 26.5, and 368 nmol/L, respectively. All these values
      decreased postoperatively. The mean anti-AchR Ab titer was significantly higher
      in Group M than in Group T (P=0.034). All five cases in Group M were found by
      post-operative pathological examination to have multifocal type A thymomas.
      CONCLUSIONS: Microscopic thymomas tend to be multifocal type A thymomas. Anti
      AchR Ab titers decreased significantly in all groups. It is very important to
      both perform complete extended thymectomies in patients with myasthenia gravis
      and pathological examination of thin slices of thymic tissue to maximize
      detection of microscopic thymomas.

PMID- 28740674
TI  - Does the usage of digital chest drainage systems reduce pleural inflammation and
      volume of pleural effusion following oncologic pulmonary resection?-A prospective
      randomized trial.
AB  - BACKGROUND: Prolonged air leak and high-volume pleural drainage are the most
      common causes for delays in chest tube removal following lung resection. While
      digital pleural drainage systems have been successfully used in the management of
      post-operative air leak, their effect on pleural drainage and inflammation has
      not been studied before. We hypothesized that digital drainage systems (as
      compared to traditional analog continuous suction), using intermittent balanced
      suction, are associated with decreased pleural inflammation and postoperative
      drainage volumes, thus leading to earlier chest tube removal. METHODS: One
      hundred and three [103] patients were enrolled and randomized to either analog
      (n=50) or digital (n=53) drainage systems following oncologic lung resection.
      Chest tubes were removed according to standardized, pre-defined protocol.
      Inflammatory mediators [interleukin-1B (IL-1B), 6, 8, tumour necrosis factor
      alpha (TNF-alpha)] in pleural fluid and serum were measured and analysed. The
      primary outcome of interest was the difference in total volume of postoperative
      fluid drainage. Secondary outcome measures included duration of chest tube in
      situ, prolonged air-leak incidence, length of hospital stay and the correlation
      between pleural effusion formation, degree of inflammation and type of drainage
      system used. RESULTS: There was no significant difference in total amount of
      fluid drained or length of hospital stay between the two groups. A trend for
      shorter chest tube duration was found with the digital system when compared to
      the analog (P=0.055). Comparison of inflammatory mediator levels revealed no
      significant differences between digital and analog drainage systems. The
      incidence of prolonged post-operative air leak was significantly higher when
      using the analog system (9 versus 2 patients; P=0.025). Lobectomy was associated
      with longer chest tube duration (P=0.001) and increased fluid drainage when
      compared to sub-lobar resection (P<0.001), regardless of drainage system.
      CONCLUSIONS: Use of post-lung resection digital drainage does not appear to
      decrease pleural fluid formation, but is associated with decreased prolonged air
      leaks. Total pleural effusion volumes did not differ with the type of drainage
      system used. These findings support previously established benefits of the
      digital system in decreasing prolonged air leaks, but the advantages do not
      appear to extend to decreased pleural fluid formation.

PMID- 28740675
TI  - Feasibility of four-arm robotic lobectomy as solo surgery in patients with
      clinical stage I lung cancer.
AB  - BACKGROUND: This study was performed to investigate the feasibility of four-arm
      robotic lobectomy (FARL) as a solo surgical technique in patients with non-small
      cell lung cancer (NSCLC). Early outcome and long-term survival of FARL were
      compared with those of video-assisted thoracoscopic lobectomy (VATL). METHODS:
      Prospective enrollment of patients with clinical stage I NSCLC undergoing FARL or
      VATL (20 patients in each group) was planned. Interim analysis for early
      postoperative outcome was performed after the initial 10 cases in each group.
      RESULTS: The study was terminated early because of safety issues in the FARL
      group after enrollment of 12 FARL and 17 VATL patients from 2011 to 2012. There
      were no differences in clinical characteristics between groups. Lobectomy time
      and total operation time were significantly longer in the FARL group (P=0.003).
      There were three life-threatening events in the FARL group (2 bleedings, 1
      bronchus tear) that necessitated thoracotomy conversion in 1 patient. There were
      no differences in other operative outcomes including pain score, complications,
      or length of hospital stay. Pathologic stage and number of dissected lymph nodes
      (LNs) were also comparable. During a follow-up of 48.9+/-9.5 months, recurrence
      was identified in 2 (16.7%) patients in FARL group and 3 (23.5%) in VATL group.
      Five-year overall survival (100% vs. 87.5%, P=0.386) and disease-free survival
      (82.5% vs. 75.6%, P=0.589) were comparable. CONCLUSIONS: FARL as solo surgery
      could not be recommended because of safety issues. It required a longer operation
      time and had no benefits over VATL in terms of early postoperative outcome or
      long-term survival.

PMID- 28740676
TI  - Segmentectomy versus lobectomy for stage I non-small cell lung cancer: a
      systematic review and meta-analysis.
AB  - BACKGROUND: In recent years, many factors have revamped the interest in
      segmentectomies as preferred procedure for stage I non-small cell lung cancer
      (NSCLC). The aim of this systematic review and meta-analysis is to compare the
      outcomes of segmentectomy versus lobectomy regarding overall survival (OS) in the
      surgical treatment of stage I NSCLC, as stated in the conclusions of the largest
      studies conducted in this field and reported to date. METHODS: The searching
      strategy was developed in EMBASE, MEDLINE and Cochrane CENTRAL from 1990 until
      December 2016. The meta-analysis was performed with the combination of the
      reported survival outcomes of the individual studies using a random effect model.
      The OS of the lobectomy group was compared with the segmentectomy group alone.
      The hazard ratio (HR) and standard error were extracted or calculated for each
      study using the Kaplan-Meier method. RESULTS: Regarding the results, most of
      these studies were based on the retrospective data. The size of the cohorts
      varied from 17 to 11,520, with a total number of 24,542 patients. The pooled HR
      was 1.04 [95% confidence interval (CI), 0.92-1.18; P=0.50]. CONCLUSIONS: The
      survival in the segmentectomy group was not inferior to patients treated with
      lobectomy. In conclusion, the current meta-analysis disclosed that
      segmentectomies produce similar survival compared to lobectomy for patients with
      stage I NSCLC. To establish the role of segmentectomy in early NSCLC, more
      evidence is needed, in particular, a large numbered, prospective, randomised
      trials, which should dissolve the uncertainties and the questions raised by
      retrospective data.

PMID- 28740677
TI  - Assessment of thoracic vasculature in patients with central bronchogenic
      carcinoma by unenhanced magnetic resonance angiography: comparison between 2D
      free-breathing TrueFISP, 2D breath-hold TrueFISP and 3D respiratory-triggered
      SPACE.
AB  - BACKGROUND: Preoperative assessment of the integrity of major thoracic vessels in
      central bronchogenic carcinoma is vital for tumor staging and treatment planning.
      Contrast-enhanced CT is currently the first choice of modality for this purpose
      in clinical practice with limitations including exposure to ionizing radiation
      and the use of iodinated contrast material. MRI has been increasingly employed
      for the staging of lung cancer. More recently, unenhanced magnetic resonance
      angiography (MRA) which is totally non-invasive and contrast-free has been
      reported able to show thoracic vessels. This study was to compare image qualities
      of three unenhanced-MRAs and to evaluate accuracy of them in assessing thoracic
      vessel invasion by using contrast-enhanced CT as a reference standard. METHODS: A
      total of 30 patients with central bronchogenic carcinoma confirmed by pathology
      were examined by CT and unenhanced MRA including 2D free-breathing (FB)-TrueFISP,
      breath-holding (BH)-TrueFISP and 3D respiratory-triggered (RT)-SPACE. Image
      qualities of pulmonary arteries and veins, thoracic aorta and vena cava were
      scored for each MRA sequence. Vessel to lung tissue signal contrast-to-noise
      ratio (CNR), vessel to tumor signal contrast ratio (VTR), and tumor to background
      signal contrast ratio (TBR) were calculated. On each method, vessel invasion was
      evaluated according to types of morphological relationships between the tumor and
      major vessels. RESULTS: The three MRAs showed no significant difference in CNR
      (P=0.518) while TrueFISP MRAs were better than SPACE in terms of VTR (P=0.000)
      and image quality (P=0.002). Excellent consistency with CT was found for all
      three MRAs in assessment of the morphological relationships between tumors and
      major vessels (FB-TrueFISP: kappa =0.821; BH-TrueFISP: kappa =0.862; RT-SPACE:
      kappa =0.811). CONCLUSIONS: Both TrueFISP and SPACE allow satisfactory
      visualization of major mediastinal and hilar vessels and are comparable to MDCT
      in assessment of vessel invasion in patients with central lung cancer. TrueFISP
      sequences are better than SPACE in regard to image quality and VTR.

PMID- 28740678
TI  - Bicuspid aortic root spared during ascending aorta surgery: an update of long
      term results.
AB  - BACKGROUND: Bicuspid aortic valve (BAV) aortopathy is well known in literature
      even if only few data exist regarding isolated supra-coronary aneurysm with
      normally functioning valve and root. Aim of this study is to clarify the long
      term fate of bicuspid aortic root spared at the time of ascending aorta surgery.
      METHODS: We identified forty-seven patients (mean age, 57+/-11 y; range, 35-81 y,
      31 males) who were treated by means of supracoronary aortic replacement in
      presence of normally functioning BAV and not significantly enlarged sinues of
      Valsalva. Clinical follow-up (mean 93+/-50 months; range, 21-207) was 98.9%
      complete. RESULTS: Freedom from cardiac death at 5- and 10-year was 95%+/-5% and
      83%+/-16%. Three surviving patients required reoperation for the development of
      aortic insufficiency [2 cases treated by aortic valve replacement (AVR)] or for
      progression of aortic stenosis (AS) [1 case treated by transcatheter aortic valve
      implantation (TAVI)]. Freedom from new procedure on aortic valve was 100% and
      94.4%+/-5.6% at 5- and 10-year. Composite event-free survival at 5- and 9-year
      was 82%+/-18% and 69%+/-30%. CONCLUSIONS: Although in the setting of a BAV,
      aortic root integrity seems to remain stable during long term follow up with low
      rate of reoperation and occurrence of new adverse event.

PMID- 28740679
TI  - Three-dimensional printing guided precise surgery for right-sided aortic arch
      associated with Kommerell's diverticulum.
AB  - Right-sided aortic arch associated with Kommerell's diverticulum is a rare
      congenital defect of aorta with complexity. The challenging surgical treatment
      calls for a direct and entire visibility of aorta and its branches which can be
      provided by the three-dimensional (3D) printing technique. A 42-year-old man with
      right-sided aortic arch, Kommerell's diverticulum and an aberrant left subclavian
      artery underwent the surgery with the guiding assistance of 3D printed model. The
      satisfying outcome suggests the novel combination of 3D printing technique and
      surgical procedure a promising perspective on treating complex aortic defect.

PMID- 28740680
TI  - Uniportal video-assisted thoracoscopic right upper lobectomy and systemic
      mediastinal lymph nodes dissection.
AB  - Along with the progresses that have been made in techniques and instruments,
      uniportal video-assisted thoracoscopic surgery (VATS) became more and more
      popular. Here, we present the operation video of a 52-year-old female with early
      stage lung cancer in the right upper lobe (RUL), who underwent uniportal VATS
      right upper lobectomy and systemic mediastinal lymph nodes dissection performed
      by our team. The video demonstrated the Uniportal VATS techniques of hilar
      anatomy, bronchus and blood vessel separation, mediastinal lymph node areas
      exploration and en-bloc dissection. Once the vision angle is properly adapted,
      techniques and instruments are mastered, and the patients are well selected,
      uniportal VATS approach can be an alternative to the conventional VATS for early
      stage lung cancer.

PMID- 28740681
TI  - A segmental labeling technique for non-intubated thoracoscopic anatomical
      segmentectomy.
AB  - Herein we present a method of pulmonary segmental labeling for non-intubated
      thoracoscopic segmentectomy assisted with artificial pneumothorax, which is
      assumed to obtain a significant colored inflation-deflation line between target
      segment and adjacent normal tissues for precise resection.

PMID- 28740682
TI  - Combined analgesic treatment of epidural and paravertebral block after thoracic
      surgery.
AB  - In pulmonary surgical practice, appropriate pain management after thoracotomy is
      essential for patient recovery and the prevention of complications. Although
      epidural analgesia (EPI) has been established for chest surgery, it has some
      limitations and contraindications. Recently, paravertebral block (PVB) was
      reported as a good alternative method with fewer side effects. Despite the
      significant effects of these two treatments, postoperative pain remains among the
      greatest patient burdens. In our institution, we apply a combination of epidural
      and PVBs after thoracic surgery to reduce pain more effectively. The purpose of
      this study was to demonstrate the safety and feasibility of our method. This
      study included patients who underwent thoracic surgery and analgesic treatment in
      our institution between November 2014 and December 2016. Per our method of PVB
      induction, the parietal pleura was peeled off with a metal suction tube and an
      extrapleural pocket was created. An epidural catheter was inserted into this
      pocket and used to inject local anesthetics continuously after surgery. The
      catheters for analgesia were removed on the 4th postoperative day. In total, 368
      patients received the combined epidural and PVBs. No severe complication was
      observed. The rate of rescue medication use in this study was lower than that in
      the historical control before adoption of this combination method; the incidence
      of pneumonia and length of hospital stay after surgery were not significantly
      different in this study from those in the historical control. In conclusion, our
      study demonstrated the safety and feasibility of the combination method of EPI
      and PVB. Acute pain after thoracic surgery may be adequately controlled using
      double analgesic regimens, including EPI and PVBs, suggesting an alternative to
      conventional modalities of EPI alone or PVB alone.

PMID- 28740683
TI  - Four arms robotic-assisted pulmonary resection-left lower lobectomy: how to do
      it.
AB  - Numerous published articles have shown the safety and efficacy of robotic lung
      resection, including lobectomy. The robotic approach offers similar survival rate
      to the open and video-assisted thoracoscopic surgery methods. Potential
      advantages provided by robotic technology, such as three-dimensional (3D) high
      quality camera, wristed tools and ergonomic ease that seems to overcome certain
      video-assisted thoracic surgery (VATS) limits have been widely described. Several
      techniques have been developed by different surgeons to perform a robotic
      lobectomy. In this study, we present our technique for performing a four-arm
      robotic lobectomy for the treatment of early stage lung cancer. This is shown in
      clear, sequential steps. We also provide an instrument preference card, some
      operative tips and a high-quality video.

PMID- 28740684
TI  - Pediatric airway surgery.
AB  - The management of pediatric airway pathology can be challenging and requires a
      dedicated team, consisting of thoracic surgeons, phoniatricians, logopedics,
      pediatricians and anesthetists. It necessitates a tailored treatment approach for
      each individual patient in order to address the minor variances that exist
      between cases. The majority of pediatric airway problems are a sequela of
      prematurity and prolonged post-partal intubation/tracheostomy. Surgical repair is
      often complicated by additional malformation or severe comorbidities. This
      comprehensive review should give an overview on most common airway problems in
      neonates and children as well as available surgical techniques.

PMID- 28740685
TI  - Minimally invasive aortic valve replacement in high risk patient groups.
AB  - Minimally invasive aortic valve replacement (AVR) aims to preserve the sternal
      integrity and improve postoperative outcomes. In low risk patients, this
      technique can be achieved with comparable mortality to the conventional approach
      and there is evidence of possible reduction in intensive care and hospital length
      of stay, transfusion requirement, renal dysfunction, improved respiratory
      function and increased patient satisfaction. In this review, we aim to asses if
      these benefits can be transferred to the high risk patient groups. We therefore,
      discuss the available evidence for the following high risk groups: elderly
      patients, re-operative surgery, poor lung function, pulmonary hypertension,
      obesity, concomitant procedures and high risk score cohorts.

PMID- 28740686
TI  - Whole lung lavage-technical details, challenges and management of complications.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar
      accumulation of surfactant material with resulting hypoxemia and reduced lung
      function. Whole lung lavage (WLL) to physically remove the proteinaceous material
      from the affected lung is the standard treatment. Since its original description
      in 1964, there have been increasing numbers of WLL procedures done worldwide and
      the technique has been variously refined and modified. When done in experienced
      centers, WLL provides long lasting benefit in the majority of patients. It is
      considered safe and effective. There are no guidelines standardizing the
      procedure. Our preferred method is to lavage one lung at a time, with the patient
      supine, filling to functional residual capacity (FRC) and repeating cycles of
      drainage and instillation with chest percussion until the effluent is clear. The
      aim of this article is to provide a detailed description of the technique,
      equipment needed and logistic considerations as well as providing a physiologic
      rationale for each step of WLL. We will also review the available data concerning
      variations of the technique described in the literature.

PMID- 28740688
TI  - A general introduction to adjustment for multiple comparisons.
AB  - In experimental research a scientific conclusion is always drawn from the
      statistical testing of hypothesis, in which an acceptable cutoff of probability,
      such as 0.05 or 0.01, is used for decision-making. However, the probability of
      committing false statistical inferences would considerably increase when more
      than one hypothesis is simultaneously tested (namely the multiple comparisons),
      which therefore requires proper adjustment. Although the adjustment for multiple
      comparisons is proposed to be mandatory in some journals, it still remains
      difficult to select a proper method suitable for the various experimental
      properties and study purposes, especially for researchers without good background
      in statistics. In the present paper, we provide a brief review on mathematical
      framework, general concepts and common methods of adjustment for multiple
      comparisons, which is expected to facilitate the understanding and selection of
      adjustment methods.

PMID- 28740687
TI  - Infections causing central airway obstruction: role of bronchoscopy in diagnosis
      and management.
AB  - Central airway obstructive infections (CAOI) are challenging medical conditions
      that may represent an advanced and complicated process of ongoing infections. The
      epidemiology of CAOI is unknown as well as the pathophysiology and the mechanism
      of development. This is due to sparse data in the literature that consists mainly
      of case reports and retrospective case series. CAOI can be caused by fungal,
      bacterial, parasitic and viral infections. Most patients with CAOI can be
      diagnosed clinically and with chest imaging, which demonstrate obstruction of the
      central airways. However, bronchoscopy is commonly used to confirm and obtain a
      specific diagnosis to guide specific therapy. In recent years, interventional
      pulmonology (IP) is becoming widely available and offer a minimally invasive
      approach for the management of central airway diseases such as cancers, benign
      strictures, and other conditions. Various bronchoscopic modalities are used to
      treat central airway obstruction (CAO), such as mechanical debulking,
      endobronchial laser therapy, electrocautery, argon plasma coagulation,
      cryotherapy, and airway stenting. In patients with CAOI, the role of therapeutic
      bronchoscopy is not clearly defined, but many isolated reports in the literature
      described bronchoscopic intervention in combination with medical therapy as the
      initial management approach. In this paper, we present cases of CAOI that
      underwent bronchoscopic intervention as part of their management. We described
      the infectious etiology, locations, bronchoscopic findings and bronchoscopic
      modalities for airway management.

PMID- 28740689
TI  - Types of biological variables.
AB  - Identification and description of variables used in any study is a necessary
      component in biomedical research. Statistical analyses rely on the type of
      variables that are involved in the study. In this short article, we introduce the
      different types of biological variables. A researcher has to be familiar with the
      type of variable he/she is dealing with in his/her research to decide about
      appropriate graphs/diagrams, summary measures and statistical analysis.

PMID- 28740690
TI  - Basic statistics with Microsoft Excel: a review.
AB  - The scientific world is enriched daily with new knowledge, due to new
      technologies and continuous discoveries. The mathematical functions explain the
      statistical concepts particularly those of mean, median and mode along with those
      of frequency and frequency distribution associated to histograms and graphical
      representations, determining elaborative processes on the basis of the
      spreadsheet operations. The aim of the study is to highlight the mathematical
      basis of statistical models that regulate the operation of spreadsheets in
      Microsoft Excel.

PMID- 28740691
TI  - How to describe univariate data.
AB  - Univariate analysis has the purpose to describe a single variable distribution in
      one sample. It is the first important step of every clinical trial. In this short
      review, we focus on this analysis, the methods that authors should use to report
      this type of data, information that they should not miss and mistakes that they
      must avoid.

PMID- 28740692
TI  - Durable complete response to nivolumab in a patient with HIV and metastatic non
      small cell lung cancer.
AB  - Programmed death 1 (PD-1) inhibitors have been shown to increase overall survival
      in non-small cell lung cancer (NSCLC) patients. HIV patients have increased
      expression of PD-1 on their T-cell surfaces. We describe a patient with well
      controlled HIV and NSCLC who underwent treatment with nivolumab and had a durable
      complete response (CR) with his viral load remaining undetectable. To date there
      is only one case report of a cancer patient with melanoma and with HIV treated
      with a programmed death ligand 1 (PD-L1) inhibitor. The majority of clinical
      trials involving PD-1 and PD-L1 inhibitors exclude HIV patients.

PMID- 28740693
TI  - Disease flare after discontinuing gefitinib in a patient with lung adenocarcinoma
      and concomitant epithelial growth factor receptor mutation and anaplastic
      lymphoma kinase translocation.
AB  - We report on a patient with lung adenocarcinoma and a concomitant epithelial
      growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK)
      translocation who developed a disease flare after discontinuing gefitinib. A 63
      year-old woman with lung adenocarcinoma and a concomitant activating EGFR
      mutation and ALK translocation was treated with first-line gefitinib. After 4
      months, she discontinued the gefitinib due to disease progression. She was
      admitted to the emergency room complaining of severe dyspnea and back pain 22
      days after discontinuing gefitinib. A chest image showed numerous hematogenous
      lung metastases and extensive bone metastasis, which was compatible with a
      previously reported disease flare after stopping EGFR tyrosine kinase inhibitors
      (TKIs). Aggravated respiratory failure and progression of multiple organ
      dysfunction led to death 26 days after discontinuing gefitinib. This was a rare
      case of a disease flare up in patient with a concomitant EGFR mutation and ALK
      translocation after discontinuing an EGFR-TKI.

PMID- 28740694
TI  - Successful management of a giant dissecting aortic aneurysm in a patient with
      Behcet's disease.
AB  - Thoracic aortic aneurysm with subsequent dissection is a very rare but dangerous
      complication of Behcet's disease, which is a systemic syndrome that can involve
      blood vessels of all sizes. Surgical experience in dealing with this complication
      in patients with Behcet's disease has been limited. We report a 20-year-old
      patient with Behcet's disease who presented with a giant dissecting thoracic
      aortic aneurysm. The patient was successfully treated with an aortic root and
      arch replacement using a frozen elephant trunk technique. Timely surgical
      intervention and appropriate long-term medical management are important for these
      patients.

PMID- 28740695
TI  - Complete spontaneous resolution of a giant bulla without rupture or infection: a
      case report and literature review.
AB  - We report a case of complete spontaneous resolution of a giant bulla without
      ipsilateral pneumothorax or overt infection accompanied by contralateral
      recurrent pneumothorax. A 67-year-old man visited the emergency room with
      dyspnea. Chest computed tomography revealed spontaneous pneumothorax on the right
      side and a giant bulla in the left anterior lung. Closed thoracostomy was
      performed and the patient was discharged. Two years later, right pneumothorax
      recurred. Bullectomy in the right lung and pleurodesis were performed. On monthly
      follow up, the giant bulla in the left lung had abruptly disappeared without any
      episode of pneumothorax or infection at one year after the operation.

PMID- 28740696
TI  - Uniportal video-assisted thoracoscopic thymectomy and resection of a giant
      thymoma in a patient witness of Jehova.
AB  - A rare case of a giant thymoma in a patient witness of Jehova treated by single
      port thoracoscopic resection is reported. A 78-year-old man with chest pain and
      mild dyspnea had been previously diagnosed with giant thymoma went to our
      hospital and asked for second opinion of operation. Computed tomography showed a
      12.5 cm * 9.5 cm * 10 cm mass in the anterior mediastinum. Under the request of
      this patient, he is only willing to receive minimal invasive surgery without
      blood transfusion. Thirty-six hours after surgical resection, the patient safely
      discharged from our hospital without complication. Pathological diagnosis
      indicated a thymoma without capsular invasion, and a diagnosis of Masaoka stage I
      thymoma was made. Giant mediastinal thymoma is not rare, but how to perform
      minimal invasive surgery without complication and blood transfusion is a great
      challenge even for an experienced surgeon.

PMID- 28740697
TI  - Successful treatment of acute respiratory failure in a patient with pulmonary
      Mycobacterium abscessus infection accompanied by organizing pneumonia.
AB  - Organizing pneumonia (OP) is an inflammatory lung disease characterized
      pathologically by the presence of buds of granulation tissue in the distal air
      spaces. There are numerous causes of OP including acute respiratory infections
      such as viral and bacterial infections. However, Mycobacterium abscessus (M.
      abscessus) has rarely been reported as a causative pathogen of OP. Here, we
      report a 67-year-old woman with rapidly progressive pulmonary M. abscessus
      infection who developed OP and acute respiratory failure (ARF). She was treated
      successfully with a corticosteroid and anti-mycobacterial therapy. Our
      observations suggest that pulmonary M. abscessus infection should be added to the
      list of infectious conditions associated with OP.

PMID- 28740698
TI  - Robotic trans-subxiphoid extended thymectomy in a patient with thymoma-associated
      pemphigus.
AB  - We herein firstly reported that a patient with thymoma-associated pemphigus (TAP)
      underwent a robotic-assisted trans-subxiphoid thoracoscopic extended thymectomy
      and then achieved stable resolution. The patient, a 47-year-old male, was first
      admitted to our hospital owing to stomatitis and bullae of the trunk after four
      months' prednisone treatment. On admission, chest computed tomography (CT)
      revealed an anterior-mediastinal mass and it was initially diagnosed as a
      thymoma. He was positive for anti-BP (bullous pemphigoid)-180 antibody and anti
      desmoglein 3 antibody. Then, a robotic-assisted thymectomy was performed,
      following which, the anti-BP-180 and anti-desmoglein 3 antibody titres have
      declined. The patient's mucocutaneous lesions improved, and the steroid dose was
      gradually decreased from 60 to 40 mg/day. According to previous reports, and the
      experience of the presented case, we therefore believe that early extended
      thymectomy is an effective therapeutic intervention for TAP.

PMID- 28740699
TI  - Prof. Malcolm M. DeCamp: declining use of surgical therapy for early stage non
      small cell lung cancer in the United States.

PMID- 28740700
TI  - Prof. Abbas E. Abbas: a robotic thoracic practice can provide both clinical and
      financial benefits for an academic institution.

PMID- 28740701
TI  - Prof. Benny Weksler: adjuvant chemotherapy improves survival.

PMID- 28740702
TI  - Dr. Sebastien Gilbert: more evidence is need for the promotion of uniportal VATS
      in North America.

PMID- 28740703
TI  - Prof. Konrad Hoetzenecker: extracorporeal life support, a bridge to lung
      transplantation.

PMID- 28740704
TI  - Is near-time prevention for sudden cardiac arrest feasible? The e-MUST score.

PMID- 28740705
TI  - A closer look at the safety and effectiveness of modern PORT in stage III-N2 non
      small cell lung cancer.

PMID- 28740706
TI  - Upstaging, not just a non-small matter.

PMID- 28740707
TI  - Preface: innovations in the management of valvular and structural heart disease.

PMID- 28740708
TI  - Staged percutaneous coronary intervention followed by minimally invasive mitral
      valve surgery versus combined coronary artery bypass graft and mitral valve
      surgery for two-vessel coronary artery disease and moderate to severe ischemic
      mitral regurgitation.
AB  - BACKGROUND: The optimal treatment for concomitant two-vessel coronary artery
      disease (CAD) and moderate to severe ischemic mitral regurgitation (IMR) remains
      unclear. We compared the results of a staged percutaneous coronary intervention
      followed by minimally invasive mitral valve surgery (PCI+MIVS) versus combined
      coronary artery bypass graft and mitral valve surgery (CABG+MVS) in this
      population. METHODS: All consecutive patients with two-vessel CAD and moderate to
      severe IMR, who underwent PCI+MIVS or CABG+MVS at our institution between
      February 2009 and April 2014, were retrospectively evaluated. RESULTS: There were
      nine patients identified who underwent PCI+MIVS, and 15 who underwent CABG+MVS,
      with a mean age of 71+/-7, and 70+/-7 years, respectively (P=0.86). The remaining
      baseline characteristics were similar between both groups, with the exception of
      a higher prevalence of pre-operative clopidogrel administration (78% versus 27%,
      P=0.03) and left anterior descending plus left circumflex CAD (78% versus 27%,
      P=0.03), in those who underwent PCI+MIVS. The PCI+MIVS approach was associated
      with decreased mean cardiopulmonary bypass (111+/-41 versus 167+/-49 min, P=0.01)
      and aortic cross-clamp (79+/-32 versus 129+/-35 min, P=0.003) times, and less
      median number of intraoperative packed red blood transfusions {2 [interquartile
      range (IQR), 0-2] versus 3 units (IQR, 1-4), P=0.05}, when compared with
      CABG+MVS. The rate of mitral valve repair, postoperative complications, 30-day
      mortality, and 1-year survival did not differ between the surgical approaches.
      CONCLUSIONS: PCI+MIVS for two-vessel CAD and moderate to severe IMR is feasible,
      and associated with satisfactory outcomes, as compared with CABG+MVS.

PMID- 28740709
TI  - Outcomes of a hybrid approach of percutaneous coronary intervention followed by
      minimally invasive aortic valve replacement.
AB  - BACKGROUND: In patients requiring coronary revascularization and aortic valve
      replacement, a combined approach of percutaneous coronary intervention followed
      by minimally invasive aortic valve replacement may be a viable treatment
      strategy. METHODS: The outcomes of 123 consecutive patients with significant
      coronary artery and aortic valve disease, who underwent percutaneous coronary
      intervention followed by elective minimally invasive aortic valve replacement
      between February 2009 and April 2014, were retrospectively evaluated. RESULTS:
      The cohort consisted of 80 males and 43 females, with a mean age of 75.7+/-8.1
      years. Drug-eluting stents were used in 69.9% of the patients, and 64.2% were on
      dual anti-platelet therapy at the time of aortic valve replacement. Within a
      median of 39 days (IQR 21-64), 83.7% of the patients underwent primary and 16.3%
      underwent re-operative minimally invasive aortic valve replacement. Post
      operatively, there was 1 (0.8%) cerebrovascular accident, 1 patient (0.8%)
      required a re-operation due to bleeding, and 2 (1.6%) developed acute kidney
      injury. Thirty-day mortality occurred in 2 (1.6%) patients. Follow-up was
      available for all of the patients, and at a mean follow-up period of 14.3+/-12.5
      months, 4 (3.3%) had an acute coronary syndrome, and 1 (0.8%) required a repeat
      target vessel revascularization. The actuarial survival rate at 1- and 3-year was
      92.7% and 89.4%, respectively. CONCLUSIONS: In a select group of patients with
      coronary artery and aortic valve disease, a combined approach of percutaneous
      coronary intervention followed by minimally invasive aortic valve replacement can
      be safely performed with excellent short-term and midterm outcomes.

PMID- 28740710
TI  - Percutaneous coronary intervention followed by minimally invasive valve surgery
      compared with median sternotomy coronary artery bypass graft and valve surgery in
      patients with prior cardiac surgery.
AB  - BACKGROUND: In patients with prior cardiac surgery requiring re-operative
      coronary and valve surgery, a hybrid approach of percutaneous coronary
      intervention followed by minimally invasive valve surgery (PCI + MIVS) may be an
      alternative to the standard median sternotomy coronary artery bypass and valve
      surgery (CABG + valve). METHODS: The outcomes of patients with prior cardiac
      surgery, presenting with coronary artery and valvular disease, who underwent PCI
      + MIVS (N=39) were retrospectively compared with those who underwent CABG + valve
      (N=28) via a repeat median sternotomy, between February 2009 and April 2014.
      RESULTS: The mean age for the PCI + MIVS versus CABG + valve group was 75+/-9 and
      72+/-11 years (P=0.54), respectively. The baseline characteristics were similar
      between groups, with the exception of a greater prevalence of 1-vessel coronary
      artery disease and clopidogrel or dual antiplatelet therapy at the time of
      surgery in the PCI + MIVS group, and more 3-vessel coronary artery disease in
      those undergoing CABG + valve surgery. The PCI + MIVS approach was associated
      with a decreased aortic cross-clamp (94 vs. 131 minutes, P=0.001) and
      cardiopulmonary bypass (128 vs. 190 minutes, P<0.001) times, fewer intraoperative
      packed red blood transfusions (1.3 vs. 3.8 units, P=0.001), shorter intensive
      care unit length of stay (41 vs. 71 hours, P<0.001), and decreased incidence of
      prolonged mechanical ventilation (12.8% vs. 35.7%, P=0.03), re-intubation (2.6%
      vs. 17.9%, P=0.04), when compared with CABG + valve. The thirty-day and two-year
      mortality were similar, being 7.7% vs. 7.1% (P=0.66), and 12.8% vs. 10.7%
      (P=0.55), in the PCI + MIVS vs. CABG + valve group, respectively. CONCLUSIONS:
      Hybrid PCI + MIVS in patients with prior cardiac surgery is associated with
      shorter operative times and intensive care unit length of stay, less need for
      intraoperative blood cell transfusions, decreased use of mechanical ventilation,
      and similar short-term and follow-up survival, when compared with CABG + valve
      surgery via median sternotomy. Randomized trials and multicenter registries are
      needed to further evaluate this approach.

PMID- 28740711
TI  - Mitral valve repair and subvalvular intervention for secondary mitral
      regurgitation: a systematic review and meta-analysis of randomized controlled and
      propensity matched studies.
AB  - BACKGROUND: Combining a ring annuloplasty (Ring) with a mitral subvalvular
      intervention (Ring + subvalvular) in patients with secondary mitral regurgitation
      (MR) may improve mitral valve (MV) repair durability. However, the outcomes of
      this strategy compared with a Ring only, have not been clearly defined. METHODS:
      A systematic review and meta-analysis was performed utilizing randomized
      controlled and propensity matched studies which compared a Ring + subvalvular
      versus Ring MV repair for the treatment of secondary MR. Risk ratio (RR),
      weighted mean difference (MD), and the 95% confidence interval (CI) were
      calculated by the Mantel-Haenszel and inverse-variance methods, for clinical
      outcomes and echocardiographic measures of follow-up MR, left ventricular (LV)
      reverse remodeling, and MV apparatus geometry. RESULTS: Five studies were
      identified, with a total of 397 patients. Baseline characteristics were similar
      between groups, and all patients had moderate to severe secondary MR, with the
      vast majority in the setting of ischemic cardiomyopathy. A Ring + subvalvular
      repair consisted of papillary muscle approximation (n=2), papillary muscle
      relocation (n=2), or secondary chordal cutting (n=1). Follow-up ranged from 10.1
      (mean range =0.25-42) to 69 [interquartile range (IQR) =23-82] months. When
      compared with Ring only at last follow-up, a Ring + subvalvular MV repair was
      associated with: (I) a smaller MR grade (MD =-0.44, 95% CI -0.69 to -0.19;
      P=0.0005); (II) a reduced risk of moderate or greater recurrent MR (RR =0.43, 95%
      CI, 0.27-0.66; P=0.0002); (III) a smaller mean LV end-diastolic diameter (MD =
      3.56 mm, 95% CI -5.40 to -1.73; P=0.0001) and a greater ejection fraction (MD
      =2.64%, 95% CI, 0.13-5.15; P=0.04); and, (IV) an improved MV apparatus geometry.
      There were no differences in operative mortality, post-operative morbidity, or
      follow-up survival between surgical approaches. CONCLUSIONS: When compared with
      Ring only, a Ring + subvalvular MV repair is associated with greater LV reverse
      remodeling and systolic function, less recurrence of moderate or greater MR, and
      an improved geometry of the MV apparatus at short and mid-term follow-up.

PMID- 28740712
TI  - Hybrid approach of percutaneous coronary intervention followed by minimally
      invasive mitral valve surgery: a 5-year single-center experience.
AB  - BACKGROUND: The current study evaluated the safety and feasibility of staged
      ("hybrid") percutaneous coronary intervention (PCI) followed by isolated
      minimally invasive mitral valve (MV) surgery [PCI + minimally invasive mitral
      valve surgery (MIMVS)], for patients with concomitant coronary artery and MV
      disease. METHODS: A total of 93 patients who underwent PCI + MIMVS for coronary
      artery and MV disease between February 2009 and April 2014 were retrospectively
      analyzed. RESULTS: There were 54 (58.1%) men and 39 (41.9%) women. The mean age
      was 73+/-8 years, and all patients had severe mitral regurgitation. PCI was
      performed for single-vessel coronary artery disease in 40 (43%) patients, two
      vessel in 49 (52.7%), and three-vessel in 4 (4.3%). Within a median of 48 days
      (IQR, 18-71) after PCI, 78 (83.9%) patients underwent primary valve surgery, and
      15 (16.1%) underwent re-operative valve surgery, with 56 (60.2%) having MV
      replacement, and 37 (39.8%) having MV repair. Sixty-five (69.9%) patients were
      being treated with dual anti-platelet therapy at the time of surgery. The median
      number of transfused intra-operative red blood cell units was 1 (IQR, 0-2), and
      the intensive care unit and hospital lengths of stay were 46 hours (IQR, 27-76)
      and 8 days (IQR, 5-11), respectively. Post-operatively, there was 1 (1.1%)
      cerebrovascular accident, 2 (2.2%) patients developed acute kidney injury, and 4
      (4.3%) required a re-operation for bleeding. Thirty-day mortality occurred in 4
      (4.3%) patients. At a mean follow-up of 15.3+/-13.2 months, 3 (3.4%) patients
      required target-vessel revascularization. The survival rate was 89% and 85% at 1
      and 3 years, respectively. CONCLUSIONS: In patients with concomitant coronary
      artery and MV disease, PCI + MIMVS can be safely performed and is associated with
      good short-term and follow-up outcomes.

PMID- 28740713
TI  - Outcomes of minimally invasive double valve surgery.
AB  - BACKGROUND: Double valve surgery is associated with an increased peri-operative
      morbidity and mortality. A less invasive right thoracotomy approach may be a
      viable alternative to median sternotomy surgery in these higher-risk patients.
      METHODS: We retrospectively analyzed the baseline demographics, operative
      characteristics, and post-operative outcomes of patients who underwent minimally
      invasive double valve surgery between January 2009 and December 2011 at our
      institution. RESULTS: The cohort consisted of 117 patients, of which 68 (58.1%)
      were female. The mean age was 73+/-11 years, and the mean left ventricular
      ejection fraction was 52+/-11%. There were 43 (36.8%) patients with a history of
      congestive heart failure, 45 (38.5%) with chronic obstructive pulmonary disease,
      and 5 (4.3%) had a history of chronic kidney disease. The patients underwent
      primary (90.6%) or re-operative (9.4%) double valve surgery, which consisted of
      50 (42.7%) aortic valve replacement and mitral valve repair, 31 (26.5%) mitral
      and tricuspid valve repair, 18 (15.4%) aortic and mitral valve replacement, 17
      (14.5%) mitral valve replacement with tricuspid valve repair, and 1 (0.9%) aortic
      valve replacement with tricuspid valve repair. Post-operatively, there were 40
      (34.2%) cases of prolonged ventilation, 9 (7.7%) acute kidney injury, 6 (5.1%) re
      operations for bleeding, 1 (0.9%) cerebrovascular accident, and 15 (12.8%) cases
      of atrial fibrillation. The mean total hospital length of stay was 12+/-12 days,
      with an in-hospital mortality of 2 (1.7%). CONCLUSIONS: A minimally invasive
      right thoracotomy approach to primary or re-operative double valve surgery is
      feasible, may be utilized with acceptable peri-operative morbidity and mortality.

PMID- 28740714
TI  - Aortic valve replacement in patients with a left ventricular ejection fraction
      <=35% performed via a minimally invasive right thoracotomy.
AB  - BACKGROUND: We evaluated the outcomes of patients with aortic valve pathology in
      the setting of a left ventricular ejection fraction <=35% who underwent minimally
      invasive aortic valve replacement (AVR), with or without concomitant mitral valve
      (MV) surgery. METHODS: All minimally invasive AVR in patients with a left
      ventricular ejection fraction <=35%, performed via a right thoracotomy for aortic
      stenosis or regurgitation between January 2009 and March 2013, were
      retrospectively evaluated. The operative characteristics, perioperative outcomes,
      and 30-day mortality were analyzed. RESULTS: There were 75 patients identified:
      51 who underwent isolated AVR, and 24 who had combined AVR plus MV surgery for
      moderate to severe mitral regurgitation. In patients undergoing MV surgery, there
      were 22 (91.7%) MV repairs [ring annuloplasty =7 (37.5%), transaortic edge-to
      edge repair =15 (62.5%)], and 2 (8.3%) replacements. No patient required
      conversion to sternotomy for inadequate surgical field exposure. The median total
      mechanical ventilation time and intensive care unit length of stay were 14 (IQR,
      8-20) and 42 hours (IQR, 26-93 hours) in the isolated AVR group, and 16.5 hours
      (IQR, 12-61.5 hours) and 95.5 hours (IQR, 43.5-159 hours) in the AVR plus MV
      surgery group, respectively. The most common post-operative complication was new
      onset atrial fibrillation, which occurred in 15 (29.4%) isolated AVR and 4
      (16.7%) AVR plus MV surgery patients. The median hospital length of stay and 30
      day mortality was 7 days (IQR, 5-12 days) and 1 (2%) in the isolated AVR group,
      and 10.5 days (IQR, 5-21 days) and 1 (4.3%) for AVR plus MV surgery. CONCLUSIONS:
      In patients with aortic valve pathology in the setting of a left ventricular
      ejection fraction <=35%, minimally invasive AVR can be performed, with or without
      concomitant MV surgery, with a low morbidity and mortality.

PMID- 28740715
TI  - Minimally invasive valve surgery in high-risk patients.
AB  - The use of minimally, or less invasive, approaches to cardiac valve surgery has
      increased over the past decade. Because of its less traumatic nature, early
      studies in lower risk patients demonstrated the approach to be associated with an
      enhanced recovery, increased patient satisfaction, and good operative outcomes.
      With time, despite a steep learning curve, surgeons expanded this approach to
      perform more complex procedures, and include patients with more co-morbidity. The
      aim of this publication is to review the current literature involving the use of
      minimally invasive valve surgery (MIVS) in higher-risk patients.

PMID- 28740716
TI  - Biomechanics raises solution to avoid geometric mitral valve configuration
      abnormalities in ischemic mitral regurgitation.
AB  - Ischemic mitral regurgitation (IMR) is a form of mitral insufficiency that is
      characterized by papillary muscle (PM) displacement, leaflet tethering, reduced
      closing forces, and different degree of annular dilatation. Treatment of this
      condition includes mitral valve replacement or mitral valve repair with
      restrictive annuloplasty. Recent evidences in mitral valve repair showed that
      addressing only the annulus and neglecting the subvalvular apparatus provides a
      suboptimal operation with poor long-term results. However, the complexity of the
      geometrical aberrances occurring in IMR demands for more accurate analysis also
      involving the biomechanics underlying the failing mitral valve and subvalvular
      apparatus. Finite element analysis (FEA) is a powerful tool in this context and
      we developed a biomechanical model of mitral valve and subvalvular unit using 3D
      geometry of the leaflets, annulus, chordae and PM. After the application of
      structural properties of materials to these elements and simulation of systemic
      pressure loading, FEA could be used to directly determine biomechanical changes
      and geometry variations. We believe this approach can provide valuable
      information to better address the surgical treatment of IMR and answer some of
      the questions still pending in IMR management.

PMID- 28740717
TI  - Hybrid repair of aortic arch aneurysms: a comprehensive review.
AB  - Open total arch replacement (TAR) has become safer with refinements in cerebral
      protection techniques. The frequent extension of aortic arch aneurysms into the
      descending thoracic aorta customarily requires a two-staged conventional elephant
      trunk procedure, carrying relatively high mortality and morbidity risks and high
      rates of rupture in the interval between the two open surgeries. The technical
      demands and invasive nature of TAR has therefore precluded many high-risk
      patients from being surgical candidates for aneurysm repair. As a result, hybrid
      techniques and approaches to the aortic arch have become common since the
      adoption of thoracic endovascular aortic repair (TEVAR) and advancement in the
      commercial grafts that are available. The results of hybrid aortic arch repairs
      have been encouraging, though with higher rates of re-interventions than TAR and
      variable reported rates of stroke and spinal cord ischemia. The aim of this
      publication is to review the current literature on hybrid repair of aortic arch
      aneurysms.

PMID- 28740718
TI  - Papillary muscle approximation in mitral valve repair for secondary MR.
AB  - Ischemic mitral regurgitation (IMR) is a complex disorder occurring after a
      myocardial infarction and affecting both the mitral valvular and subvalvular
      apparati. Several abnormalities can be detected in IMR as annular dilatation,
      leaflet tethering with impaired coaptation and papillary muscle (PM) displacement
      along a posterior, apical or lateral vectors. Treatments available include,
      beside myocardial revascularization, mitral-valve repair or chordal-sparing
      replacement. Repair is normally achieved downsizing the mitral valve annulus with
      a rigid or semirigid ring. However, considering the involvement of the
      subvalvular apparatus, techniques addressing the PM have been developed. The
      rationale at the basis of this strategy relies in the possibility to reduce the
      interpapillary muscle distance restoring the geometry of the left ventricle (LV)
      and ultimately resolving the leaflet tethering at the basis of IMR. Subvalvular
      apparatus surgical approaches include the papillary muscle approximation (PMA),
      surgical relocation and PM sling. Improved outcomes in terms of postoperative
      positive left ventricular remodeling and recurrence of mitral regurgitation have
      been reported, but more investigations are required to confirm the efficacy of
      subvalvular apparatus surgery. Application of finite element analysis to improve
      preoperative and intraoperative planning and achieve a correct and durable repair
      by means of subvalvular surgery is an exciting new avenue in IMR research.

PMID- 28740720
TI  - Analysing the reasons of failure of surgical mitral repair approaches-do we need
      to better think in biomechanics?
AB  - The failure of mitral valve repair procedures revealed in the outcomes of the
      recent randomized studies is suggesting the necessity for a better understanding
      of the biomechanical mechanisms underlying the failure of the surgical
      approaches. Use of biomechanical modelling and finite element analysis (FEA) in
      cardiovascular research is an important aid in this context. In our group we
      developed a biomechanical model taking into account all the component of the
      mitral valve functional unit including the valve leaflets, the annulus, the
      papillary muscles, the chordae tendinea and the ventricular geometry. The two
      dimensional mathematical model was capable to predict some of the actual
      geometrical and mechanical features of the valvular and subvalvular apparatuses
      in physiological and pathological conditions providing the engineering
      quantitative relations between closing and tethering forces and the mechanisms
      governing the mitral valve unit function. This model might further become patient
      specific by means of 3D reconstruction of clinical imaging. Images are first
      converted in a standard vector format (DICOM, etc.), then automatically
      translated in a "structural" finite element model and finally implemented in a
      finite element code. This allows for in silico simulations to virtually explore
      the effects of different surgical approaches at an early stage after the
      procedure, to help the operative decision processes, or to optimize the design of
      surgical implants.

PMID- 28740721
TI  - Cardioband for the treatment of secondary mitral regurgitation: a viable
      percutaneous option?

PMID- 28740719
TI  - Multimodality imaging assessment of mitral valve anatomy in planning for mitral
      valve repair in secondary mitral regurgitation.
AB  - Secondary mitral regurgitation (MR) is frequent valvular heart disease and
      conveys worse prognostic. Therapeutic surgical or percutaneous options are
      available in the context of severe symptomatic secondary MR, but the best
      approach to treat these patients remains unclear, given the lack of clear
      clinical evidence of benefit. A comprehensive evaluation of the mitral valve
      apparatus and the left ventricle (LV) has the ability to clearly define and
      characterize the disease, and thus determine the best option for the patient to
      improve its clinical outcomes, as well as quality of life and symptoms. The
      current report reviews the mitral valve (MV) anatomy, the underlying mechanisms
      associated with secondary MR, the related therapeutic options available, and
      finally the usefulness of a multimodality imaging approach for the planning of
      surgical or percutaneous mitral valve intervention.

PMID- 28740722
TI  - Transcatheter mitral valve replacement: an evolution of a revolution.

PMID- 28740723
TI  - At the Interface of Three Nucleic Acids: The Role of RNA-Binding Proteins and
      Poly(ADP-ribose) in DNA Repair.
AB  - RNA-binding proteins (RBPs) regulate RNA metabolism, from synthesis to decay.
      When bound to RNA, RBPs act as guardians of the genome integrity at different
      levels, from DNA damage prevention to the post-transcriptional regulation of gene
      expression. Recently, RBPs have been shown to participate in DNA repair. This
      fact is of special interest as DNA repair pathways do not generally involve RNA.
      DNA damage in higher organisms triggers the formation of the RNA-like polymer -
      poly(ADP-ribose) (PAR). Nucleic acid-like properties allow PAR to recruit DNA-
      and RNA-binding proteins to the site of DNA damage. It is suggested that poly(ADP
      ribose) and RBPs not only modulate the activities of DNA repair factors, but that
      they also play an important role in the formation of transient repairosome
      complexes in the nucleus. Cytoplasmic biomolecules are subjected to similar
      sorting during the formation of RNA assemblages by functionally related mRNAs and
      promiscuous RBPs. The Y-box-binding protein 1 (YB-1) is the major component of
      cytoplasmic RNA granules. Although YB-1 is a classic RNA-binding protein, it is
      now regarded as a non-canonical factor of DNA repair.

PMID- 28740724
TI  - Glutamyl Endopeptidases: The Puzzle of Substrate Specificity.
AB  - Glutamyl endopeptidases (GEPases) are chymotrypsin-like enzymes that
      preferentially cleave the peptide bonds of the alpha-carboxyl groups of glutamic
      acid. Despite the many years of research, the structural determinants underlying
      the strong substrate specificity of GEPases still remain unclear. In this review,
      data concerning the molecular mechanisms that determine the substrate preference
      of GEPases is generalized. In addition, the biological functions of and modern
      trends in the research into these enzymes are outlined.

PMID- 28740725
TI  - Huntington's Disease: Calcium Dyshomeostasis and Pathology Models.
AB  - Huntington's disease (HD) is a severe inherited neurodegenerative disorder
      characterized by motor dysfunction, cognitive decline, and mental impairment. At
      the molecular level, HD is caused by a mutation in the first exon of the gene
      encoding the huntingtin protein. The mutation results in an expanded
      polyglutamine tract at the N-terminus of the huntingtin protein, causing the
      neurodegenerative pathology. Calcium dyshomeostasis is believed to be one of the
      main causes of the disease, which underlies the great interest in the problem
      among experts in molecular physiology. Recent studies have focused on the
      development of animal and insect HD models, as well as patient-specific induced
      pluripotent stem cells (HD-iPSCs), to simulate the disease's progression. Despite
      a sesquicentennial history of HD studies, the issues of diagnosis and
      manifestation of the disease have remained topical. The present review addresses
      these issues.

PMID- 28740727
TI  - Structure Modeling of Human Tyrosyl-DNA Phosphodiesterase 1 and Screening for Its
      Inhibitors.
AB  - The DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) represents a
      potential molecular target for anticancer therapy. A human Tdp1 model has been
      constructed using the methods of quantum and molecular mechanics, taking into
      account the ionization states of the amino acid residues in the active site and
      their interactions with the substrate and competitive inhibitors. The
      oligonucleotide- and phosphotyrosine-binding cavities important for the inhibitor
      design have been identified in the enzyme's active site. The developed molecular
      model allowed us to uncover new Tdp1 inhibitors whose sulfo group is capable of
      occupying the position of the 3'-phosphate group of the substrate and forming
      hydrogen bonds with Lys265, Lys495, and other amino acid residues in the
      phosphotyrosine binding site.

PMID- 28740726
TI  - C2H2 Zinc Finger Proteins: The Largest but Poorly Explored Family of Higher
      Eukaryotic Transcription Factors.
AB  - The emergence of whole-genome assays has initiated numerous genome-wide studies
      of transcription factor localizations at genomic regulatory elements (enhancers,
      promoters, silencers, and insulators), as well as facilitated the uncovering of
      some of the key principles of chromosomal organization. However, the proteins
      involved in the formation and maintenance of the chromosomal architecture and the
      organization of regulatory domains remain insufficiently studied. This review
      attempts to collate the available data on the abundant but still poorly
      understood family of proteins with clusters of the C2H2 zinc finger domains. One
      of the best known proteins of this family is a well conserved protein known as
      CTCF, which plays a key role in the establishment of the chromosomal architecture
      in vertebrates. The distinctive features of C2H2 zinc finger proteins include
      strong and specific binding to a long and unique DNA recognition target sequence
      and rapid expansion within various animal taxa during evolution. The reviewed
      data support a proposed model according to which many of the C2H2 proteins have
      functions that are similar to those of the CTCF in the organization of the
      chromatin architecture.

PMID- 28740728
TI  - Dipole Modifiers Regulate Lipid Lateral Heterogeneity in Model Membranes.
AB  - In this study we report on experimental observations of giant unilamellar
      liposomes composed of ternary mixtures of cholesterol (Chol), phospholipids with
      relatively low Tmelt (DOPC, POPC, or DPoPC) and high Tmelt (sphingomyelin (SM),
      or tetramyristoyl cardiolipin (TMCL)) and their phase behaviors in the presence
      and absence of dipole modifiers. It was shown that the ratios of liposomes
      exhibiting noticeable phase separation decrease in the series POPC, DOPC, DPoPC
      regardless of any high-Tmelt lipid. Substitution of SM for TMCL led to increased
      lipid phase segregation. Taking into account the fact that the first and second
      cases corresponded to a reduction in the thickness of the lipid domains enriched
      in low- and high-Tmelt lipids, respectively, our findings indicate that the phase
      behavior depends on thickness mismatch between the ordered and disordered
      domains. The dipole modifiers, flavonoids and styrylpyridinium dyes, reduced the
      phase segregation of membranes composed of SM, Chol, and POPC (or DOPC). The
      other ternary lipid mixtures tested were not affected by the addition of dipole
      modifiers. It is suggested that dipole modifiers address the hydrophobic mismatch
      through fluidization of the ordered and disordered domains. The ability of a
      modifier to partition into the membrane and fluidize the domains was dictated by
      the hydrophobicity of modifier molecules, their geometric shape, and the packing
      density of domain-forming lipids. Phloretin, RH 421, and RH 237 proved the most
      potent among all the modifiers examined.

PMID- 28740729
TI  - Role of the Inserted alpha-Helical Domain in E. coli ATP-Dependent Lon Protease
      Function.
AB  - Multidomain ATP-dependent Lon protease of E. coli (Ec-Lon) is one of the key
      enzymes of the quality control system of the cellular proteome. A recombinant
      form of Ec-Lon with deletion of the inserted characteristic alpha-helical HI(CC)
      domain (Lon-dHI(CC)) has been prepared and investigated to understand the role of
      this domain. A comparative study of the ATPase, proteolytic, and peptidase
      activities of the intact Lon protease and Lon-dHI(CC) has been carried out. The
      ability of the enzymes to undergo autolysis and their ability to bind DNA have
      been studied as well. It has been shown that the HI(CC) domain of Ec-Lon protease
      is required for the formation of a functionally active enzyme structure and for
      the implementation of protein-protein interactions.

PMID- 28740730
TI  - Bacteriolytic Activity Of Human Interleukin-2, Chicken Egg Lysozyme In The
      Presence Of Potential Effectors.
AB  - The bacteriolytic activity of interleukin-2 and chicken egg lysozyme in the
      presence of various substances has been studied. Glycine and lysine do not affect
      the activity of interleukin-2 but increase that of lysozyme, showing a bell-shape
      concentration dependence peaking at 1.5 mM glycine and 18 mM lysine. Arginine and
      glutamate activate both interleukin-2 and lysozyme with a concentration
      dependence of the saturation type. Aromatic amino acids have almost no effect on
      the activity of both interleukin-2 and lysozyme. Aromatic amines, tryptamine, and
      tyramine activate interleukin-2 but inhibit lysozyme. Peptide antibiotics affect
      interleukin and lysozyme similarly and exhibit maximum activity in the micromolar
      range of antibiotics. Taurine has no effect on the activity of interleukin-2 and
      lysozyme. Mildronate showed no influence on lysozyme, but it activated
      interleukin-2 with the activity maximum at 3 mM. EDTA activates both interleukin
      2 and lysozyme at concentrations above 0.15 mM.

PMID- 28740731
TI  - Comparing New-Generation Candidate Vaccines against Human Orthopoxvirus
      Infections.
AB  - The lack of immunity to the variola virus in the population, increasingly more
      frequent cases of human orthopoxvirus infection, and increased risk of the use of
      the variola virus (VARV) as a bioterrorism agent call for the development of
      modern, safe vaccines against orthopoxvirus infections. We previously developed a
      polyvalent DNA vaccine based on five VARV antigens and an attenuated variant of
      the vaccinia virus (VACV) with targeted deletion of six genes (VACDelta6).
      Independent experiments demonstrated that triple immunization with a DNA vaccine
      and double immunization with VACDelta6 provide protection to mice against a
      lethal dose (10 LD50) of the ectromelia virus (ECTV), which is highly pathogenic
      for mice. The present work was aimed at comparing the immunity to smallpox
      generated by various immunization protocols using the DNA vaccine and VACDelta6.
      It has been established that immunization of mice with a polyvalent DNA vaccine,
      followed by boosting with recombinant VACDelta6, as well as double immunization
      with VACDelta6, induces production of VACV-neutralizing antibodies and provides
      protection to mice against a 150 LD50 dose of ECTV. The proposed immunization
      protocols can be used to develop safe vaccination strategies against smallpox and
      other human orthopoxvirus infections.

PMID- 28740732
TI  - Low-Molecular-Weight NGF Mimetic Corrects the Cognitive Deficit and Depression
      like Behavior in Experimental Diabetes.
AB  - Based on the comorbidity of diabetes, depression, and dementia and recognizing
      that a deficiency of the nerve growth factor (NGF) is involved in all of these
      kinds of pathologies, we studied the effect of the mimetic of dimeric dipeptide
      NGF loop 4, GK-2, on a model of streptozotocin-induced type 2 diabetes in C57Bl/6
      mice. GK-2 [hexamethylenediamide bis-(N-monosuccinyl-glutamyl-lysine)] was
      synthesized at the V.V. Zakusov Scientific Research Institute of Pharmacology.
      The study revealed the ability of GK-2 to ameliorate hyperglycemia induced by
      streptozotocine (STZ 100 mg/kg i.p.) in C57Bl/6 mice, to restore learning ability
      in the Morris Water Maze test, and to overcome depression after both
      intraperitoneal (0.5 mg/kg) and peroral (5 mg/kg) long-term administration. The
      presence of the listed properties and their preservation in the case of peroral
      treatment determines the prospects of research. Taking into account the previous
      findings on the ability of GK-2 to selectively activate PI3K/Akt, these data
      suggest that Akt-signaling is sufficient for pancreatic beta cell function. GK-2
      has been shown to exhibit pronounced neuroprotective activity. The coexistence of
      neuroprotective and antidiabetic effects is in agreement with the fundamental
      concept holding that the function of neurons and pancreatic beta cells is
      controlled by similar mechanisms.

PMID- 28740733
TI  - When Is Evidence Enough Evidence? A Systematic Review and Meta-Analysis of the
      Trabectome as a Solo Procedure in Patients with Primary Open-Angle Glaucoma.
AB  - The purpose of this systematic review and meta-analysis was to examine the
      availability of evidence for one of the earliest available minimally invasive
      glaucoma surgery (MIGS) procedures, the Trabectome. Various databases were
      searched up to December 20, 2016, for any published studies assessing the use of
      the Trabectome as a solo procedure in patients with primary open-angle glaucoma
      (POAG). The standardized mean differences (SMD) were calculated for the change in
      intraocular pressure (IOP) and number of glaucoma mediations used at 1-month, 6
      month, and 12-month follow-up. After screening, three studies and one abstract
      with analyzable data were included. The meta-analysis showed statistically
      significant reductions in IOP and number of glaucoma medications used at all time
      points. Though the Trabectome as a solo procedure appears to lower IOP and
      reduces the number of glaucoma medications, more high-quality studies are
      required to make definitive conclusions. The difficulty of obtaining evidence may
      be one of the many obstacles that limit a full understanding of the potential
      safety and/or efficacy benefits compared to standard treatments. The time has
      come for a thoughtful and integrated approach with stakeholders to determine
      optimal access to care strategies for our patients.

PMID- 28740734
TI  - Effect of Topical Nepafenac on Central Foveal Thickness following Panretinal
      Photocoagulation in Diabetic Patients.
AB  - PURPOSE: To evaluate effectiveness of topical nepafenac in reducing macular edema
      following panretinal photocoagulation (PRP). DESIGN: Prospective randomized
      double-blinded controlled study. METHODS: Sixty eyes of 60 patients having
      proliferative or severe nonproliferative diabetic retinopathy had PRP. Patients
      were then divided into two groups: nepafenac group (30 eyes) receiving 1% topical
      nepafenac eye drops for 6 months and control group (30 eyes) receiving
      carboxymethylcellulose eye drops for 6 months. Best-corrected visual acuity
      (BCVA) and macular optical coherence tomography were followed up at 1, 2, 4, and
      6 months after PRP. RESULTS: BCVA was significantly better in nepafenac group
      than in control group at all follow-ups (P < 0.01). At 6 months post-PRP, logMAR
      BCVA was 0.11 +/- 0.04 (equivalent to 20/26 Snellen acuity) in the nepafenac
      group and 0.18 +/- 0.08 (equivalent to 20/30 Snellen acuity) in the control group
      (P < 0.01). Central foveal thickness (CFT) increased in both groups from the
      first month after PRP. Increase in CFT was higher in control group than in
      nepafenac group throughout follow-up, but the difference became statistically
      significant only after 4 months. No significant ocular adverse events were
      reported with topical nepafenac. CONCLUSION: Topical nepafenac can minimize
      macular edema and stabilize visual acuity following PRP for diabetic patients.

PMID- 28740735
TI  - Structure and Function Relationship of Activated Retinal Glia in Primary Open
      Angle Glaucoma Patients.
AB  - PURPOSE: To evaluate clinically activated retinal astrocytes and Muller cells
      (ARAM) regarding retinal sensitivity and retinal nerve fiber layer (RNFL)
      thickness in primary open-angle glaucoma (POAG). METHODS: Central visual field
      (VF; i.e., retinal sensitivity) was measured with a custom-made macular pattern
      by microperimetry and correlated with the presence (ARAM+) or absence (ARAM-) of
      ARAM on red-free fundus photography and with the corresponding RNFL by optical
      coherence tomography (OCT). RESULTS: In the eyes of POAG patients, ARAM+ had
      overall a significantly lower retinal sensitivity (ARAM+: 7.34 dB, ARAM-: 11.9
      dB; p < 0.001) and lower RNFL thickness in the inferior peripapillary quadrants
      compared to ARAM- (RNFL superior: ARAM+ 74.2 MUm, ARAM- 77.5 MUm; RNFL temporal:
      ARAM+ 46.8 MUm, ARAM- 53.0 MUm, p < 0.001; and RNFL inferior: ARAM+ 63.2 MUm,
      ARAM- 73.1 MUm, p < 0.001). Within the same eye, ARAM+ showed a lower retinal
      sensitivity compared to ARAM- ([ARAM- (11.13 dB)] - [ARAM+ (9.56 dB) = 1.57 dB; p
      = 0.25). The proportion of ARAM+ per eye correlated strongly with reduced retinal
      light sensitivity (p = 0.02), corresponding lower peripapillary RNFL thickness (p
      = 0.02), and lower RNFL temporal quadrant thickness (p < 0.01), but not with
      greater age (p = 0.45). CONCLUSION: ARAM was more frequently identified in the
      eyes with a lower retinal sensitivity and peripapillary RNFL thickness and may be
      a clinical sign in the macula for an advanced stage of POAG.

PMID- 28740736
TI  - Capability of Ophthalmology Residents to Detect Glaucoma Using High-Dynamic-Range
      Concept versus Color Optic Disc Photography.
AB  - BACKGROUND: Assessment of color disc photograph (C-DP) is affected by image
      quality, which decreases the ability to detect glaucoma. High-dynamic-range (HDR)
      imaging provides a greater range of luminosity. Therefore, the objective of this
      study was to evaluate the capability of ophthalmology residents to detect
      glaucoma using HDR-concept disc photography (HDR-DP) compared to C-DP. DESIGN:
      Cross-sectional study. METHODS: Twenty subjects were classified by 3 glaucoma
      specialists as either glaucoma, glaucoma suspect, or control. All C-DPs were
      converted to HDR-DPs and randomly presented and assessed by 10 first-year
      ophthalmology residents. Sensitivity and specificity of glaucoma detection were
      compared. RESULTS: The mean +/- SD of averaged retinal nerve fiber layer (RNFL)
      thickness was 74.0 +/- 6.1 MUm, 100.2 +/- 9.6 MUm, and 105.8 +/- 17.2 MUm for
      glaucoma, glaucoma suspect, and controls, respectively. The diagnostic
      sensitivity of HDR-DP was higher than that of C-DP (87% versus 68%, mean
      difference: 19.0, 95% CI: 4.91 to 33.1; p = 0.014). Regarding diagnostic
      specificity, HDR-DP and C-DP yielded 46% and 75% (mean difference: 29.0, 95% CI:
      13.4 to 44.6; p = 0.002). CONCLUSIONS: HDR-DP statistically increased diagnostic
      sensitivity but not specificity. HDR-DP may be a screening tool for nonexpert
      ophthalmologists.

PMID- 28740737
TI  - Clinical Characteristics and Risk Factors of Recurrent Mooren's Ulcer.
AB  - PURPOSE: To investigate the clinical characteristics of Mooren's ulcer in East
      China and to identify the potential risk factors that affect the recurrence of
      Mooren's ulcer. METHODS: We reviewed the medical records of 95 patients (100
      eyes) diagnosed with Mooren's ulcer from May 2005 to December 2014. The patients
      were classified into recurrent and nonrecurrent groups and followed up for 18
      months. The difference between two groups was estimated. The patients in the
      recurrent group were subdivided according to the history of corneal infection and
      corneal perforation, respectively. The recurrent time in the subgroups was
      analyzed. RESULTS: Patients in the recurrent group were more likely to have a
      history of corneal infection and corneal perforation than that in the
      nonrecurrent groups. In patients with recurrent Mooren's ulcer, the median time
      to first recurrence was 130 days in the infection group, 480 days in noninfection
      group, and 195 days in the perforation group versus 480 days in nonperforation
      group. CONCLUSION: Corneal infection and corneal perforation were associated with
      early recurrence of Mooren's ulcer. The tailored follow-up schedule should be
      used for patients with corneal infection and corneal perforation due to the high
      risk of recurrence.

PMID- 28740738
TI  - Shorter Leukocyte Telomere Length in Relation to Presumed Nonalcoholic Fatty
      Liver Disease in Mexican-American Men in NHANES 1999-2002.
AB  - Leukocyte telomere length is shorter in response to chronic disease processes
      associated with inflammation such as diabetes mellitus and coronary artery
      disease. Data from the National Health and Nutrition Examination Survey (NHANES)
      from 1999 to 2002 was used to explore the relationship between leukocyte telomere
      length and presumed NAFLD, as indicated by elevated serum alanine
      aminotransferase (ALT) levels, obesity, or abdominal obesity. Logistic regression
      models were used to evaluate the relationship between telomere length and
      presumed markers of NAFLD adjusting for possible confounders. There was no
      relationship between elevated ALT levels, abdominal obesity, or obesity and
      telomere length in adjusted models in NHANES (OR 1.13, 95% CI 0.48-2.65; OR 1.17,
      95% CI 0.52-2.62, resp.). Mexican-American men had shorter telomere length in
      relation to presumed NAFLD (OR 0.07, 95% CI 0.006-0.79) and using different
      indicators of NAFLD (OR 0.012, 95% CI 0.0006-0.24). Mexican origin with presumed
      NAFLD had shorter telomere length than men in other population groups.
      Longitudinal studies are necessary to evaluate the role of telomere length as a
      potential predictor to assess pathogenesis of NALFD in Mexicans.

PMID- 28740739
TI  - A Combined Water Extract of Frankincense and Myrrh Alleviates Neuropathic Pain in
      Mice via Modulation of TRPV1.
AB  - Frankincense and myrrh are widely used in clinics as a pair of herbs to obtain a
      synergistic effect for relieving pain. To illuminate the analgesia mechanism of
      frankincense and myrrh, we assessed its effect in a neuropathic pain mouse model.
      Transient receptor potential vanilloid 1 (TRPV1) plays a crucial role in
      neuropathic pain and influences the plasticity of neuronal connectivity. We
      hypothesized that the water extraction of frankincense and myrrh (WFM) exerted
      its analgesia effect by modulating the neuronal function of TRPV1. In our study,
      WFM was verified by UHPLC-TQ/MS assay. In vivo study showed that nociceptive
      response in mouse by heat and capsaicin induced were relieved by WFM treatment.
      Furthermore, thermal hypersensitivity and mechanical allodynia were also
      alleviated by WFM treatment in a chronic constriction injury (CCI) mouse model.
      CCI resulted in increased TRPV1 expression at both the mRNA and protein levels in
      predominantly small-to-medium neurons. However, after WFM treatment, TRPV1
      expression was reverted in real-time PCR, Western blot, and immunofluorescence
      experiments. Calcium response to capsaicin was also decreased in cultured DRG
      neurons from CCI model mouse after WFM treatment. In conclusion, WFM alleviated
      CCI-induced mechanical allodynia and thermal hypersensitivity via modulating
      TRPV1.

PMID- 28740741
TI  - Ten-Year Follow-Up of a Fragment Reattachment to an Anterior Tooth: A
      Conservative Approach.
AB  - This report describes the 10-year follow-up data of a patient who underwent
      fragment reattachment to the maxillary central incisor after coronal fracture
      with pulp exposure as well as the procedures followed for functional and esthetic
      adjustments. A 9-year-old female patient presented at the clinic of dentistry at
      the State University of Rio de Janeiro with a coronal fracture and pulp exposure
      of the right maxillary central incisor that had occurred immediately after an
      accident. The intact tooth fragment was recovered at the accident site and stored
      in milk. The treatment plan followed was to perform direct pulp capping and tooth
      fragment reattachment. When the patient was 14 years old, adhesion between
      fragment and remaining tooth was lost, and fragment reattachment was performed.
      Five years later, the same tooth presented clinical discoloration and absence of
      sensitivity during pulp vitality tests. Subsequently, a new treatment plan was
      formulated, which included endodontic treatment, followed by nonvital tooth
      bleaching and light-cured composite resin restoration. An esthetic and natural
      looking restoration was achieved. Tooth fragment reattachment is not a temporary
      restorative technique and requires functional and esthetic adjustments over time
      to maintain the biomimetic characteristics of traumatized anterior teeth and
      predictable outcomes.

PMID- 28740740
TI  - Environmental Factors Promoting Neural Plasticity: Insights from Animal and Human
      Studies.
AB  - We do not all grow older in the same way. Some individuals have a cognitive
      decline earlier and faster than others who are older in years but cerebrally
      younger. This is particularly easy to verify in people who have maintained
      regular physical activity and healthy and cognitively stimulating lifestyle and
      even in the clinical field. There are patients with advanced neurodegeneration,
      such as Alzheimer's disease (AD), that, despite this, have mild cognitive
      impairment. What determines this interindividual difference? Certainly, it cannot
      be the result of only genetic factors. We are made in a certain manner and what
      we do acts on our brain. In fact, our genetic basis can be modulated, modified,
      and changed by our experiences such as education and life events; daily, by sleep
      schedules and habits; or also by dietary elements. And this can be seen as true
      even if our experiences are indirectly driven by our genetic basis. In this
      paper, we will review some current scientific research on how our experiences are
      able to modulate the structural organization of the brain and how a healthy
      lifestyle (regular physical activity, correct sleep hygiene, and healthy diet)
      appears to positively affect cognitive reserve.

PMID- 28740742
TI  - Radical Surgery of Only the Anterior Elements of the Spine at the Posterior
      Element Fusion Level due to Metastatic Thyroid Cancer.
AB  - Spinal metastasis of differentiated thyroid cancer can have a favorable prognosis
      if radical surgery is performed. We encountered a case of spinal metastasis
      involving three anterior vertebral bodies at the posterior element fusion level
      and successfully achieved adequate stability by radical surgery involving only
      the anterior elements. A 67-year-old woman who had numbness and muscle weakness
      in the lower limbs caused by metastatic spinal tumor at the posterior element
      fusion level of L1-L3 vertebrae was treated with radical surgery of only the
      anterior element to gain stability. Similar situations may occur in cases
      involving other malignant tumor metastases or spinal primary tumors. If such a
      case occurs, this method could be useful in preventing metastasis to the
      posterior element.

PMID- 28740743
TI  - An Obstructing Small Bowel Phytobezoar in an Elderly Female Nigerian: A Case
      Report and Literature Review.
AB  - Small bowel obstruction secondary to phytobezoars is an unusual presentation in
      surgery. We present a case of an elderly female patient with an insidious onset
      of abdominal pain, abdominal distension, and bilious vomiting diagnosed
      radiologically to be small bowel obstruction. Exploratory laparotomy revealed a
      trapped mass of vegetable matter in the distal ileum. She had enterotomy with
      primary closure for removal of obstructing ileal phytobezoars. Her postoperative
      recovery was uneventful.

PMID- 28740744
TI  - Hippocampal volume as an amplifier of the effect of social context on adolescent
      depression.
AB  - Recent models have focused on how brain-based individual differences in social
      sensitivity shape affective development in adolescence, when rates of depression
      escalate. Given the importance of the hippocampus in binding contextual and
      affective elements of experience, as well as its putative role in depression, we
      examined hippocampal volume as a moderator of the effects of social context on
      depressive symptoms in a sample of 209 Mexican-origin adolescents. Adolescents
      with larger versus smaller hippocampal volumes showed heightened sensitivity in
      their depressive symptoms to a protective factor inside the home (sense of family
      connectedness) and a risk factor outside of it (community crime exposure). These
      interactive effects uniquely predicted depressive symptoms and were greater for
      the left side, suggesting two independent social-contextual contributions to
      depression that were moderated by left hippocampal volume. Results elucidate
      complex brain-environment interplay in adolescent depression, offering clues
      about for whom and how social context plays a role.

PMID- 28740745
TI  - Investigating the running abilities of Tyrannosaurus rex using stress-constrained
      multibody dynamic analysis.
AB  - The running ability of Tyrannosaurus rex has been intensively studied due to its
      relevance to interpretations of feeding behaviour and the biomechanics of scaling
      in giant predatory dinosaurs. Different studies using differing methodologies
      have produced a very wide range of top speed estimates and there is therefore a
      need to develop techniques that can improve these predictions. Here we present a
      new approach that combines two separate biomechanical techniques (multibody
      dynamic analysis and skeletal stress analysis) to demonstrate that true running
      gaits would probably lead to unacceptably high skeletal loads in T. rex.
      Combining these two approaches reduces the high-level of uncertainty in previous
      predictions associated with unknown soft tissue parameters in dinosaurs, and
      demonstrates that the relatively long limb segments of T. rex-long argued to
      indicate competent running ability-would actually have mechanically limited this
      species to walking gaits. Being limited to walking speeds contradicts arguments
      of high-speed pursuit predation for the largest bipedal dinosaurs like T. rex,
      and demonstrates the power of multiphysics approaches for locomotor
      reconstructions of extinct animals.

PMID- 28740746
TI  - Physiological epicotyl dormancy and its alleviation in seeds of Yunnanopilia
      longistaminea: the first report of physiological epicotyl dormancy in China.
AB  - Yunnanopilia longistaminea is an endangered monotypic species belonging to
      Opiliaceae. This edible plant is an important germplasm source with a high
      economic value in China if propagation were less difficult. Seed dormancy and
      germination of this species were investigated to improve propagation. Considering
      seeds have a fully developed embryo and mature and are dispersed in summer, and
      radicles and epicotyls emerge the following autumn and next spring, respectively,
      we hypothesized that Y. longistaminea seeds may undergo physiological epicotyl
      dormancy. Seed moisture content and viability decreased as dehydration occurred.
      Thus, the seeds may be recalcitrant. The seed germination of this species
      involves two stages: radicle emergence and epicotyl (shoot) emergence. The
      optimum temperature was 28  degrees C and 28  degrees C/20  degrees C to radicle
      emergence. The optimum GA3 solution for the seeds undergoing shoot emergence was
      100 mg L-1. The percentages of shoot emergence in seven and 14 days
      stratification at 5  degrees C were slightly higher than those in other groups.
      This study is the first to describe physiological epicotyl dormancy in Y.
      longistaminea seeds. Under natural conditions, seeds are subjected to Y.
      longistaminea a autumn -> winter -> spring temperature. Warm moist conditions and
      cold stratification can improve radicle emergence and alleviate epicotyl
      dormancy, respectively. The duration of cold stratification also significantly
      affects the epicotyl dormancy release of Y. longistaminea. Optimal dormancy
      breakage methods are warm (28  degrees C/20  degrees C) -> cold (5  degrees C) ->
      GA3(100 mg L-1) -> warm (28  degrees C/20  degrees C).

PMID- 28740747
TI  - In vitro assessment of anti-proliferative effect induced by alpha-mangostin from
      Cratoxylum arborescens on HeLa cells.
AB  - Natural medicinal products possess diverse chemical structures and have been an
      essential source for drug discovery. Therefore, in this study, alpha-mangostin
      (AM) is a plant-derived compound was investigated for the apoptotic effect on
      human cervical cancer cells (HeLa). The cytotoxic effects of AM on the viability
      of HeLa and human normal ovarian cell line (SV40) were evaluated by using MTT
      assay. Results showed that AM inhibited HeLa cells viability at concentration-
      and time-dependent manner with IC50 value of 24.53 +/- 1.48 uM at 24 h. The
      apoptogenic effects of AM on HeLa were assessed using fluorescence microscopy
      analysis. The effect of AM on cell proliferation was also studied through
      clonogenic assay. ROS production evaluation, flow cytometry (cell cycle)
      analysis, caspases 3/7, 8, and 9 assessment and multiple cytotoxicity assays were
      conducted to determine the mechanism of cell apoptosis. This was associated with
      G2/M phase cell cycle arrest and elevation in ROS production. AM induced
      mitochondrial apoptosis which was confirmed based on the significant increase in
      the levels of caspases 3/7 and 9 in a dose-dependent manner. Furthermore, the MMP
      disruption and increased cell permeability, concurrent with cytochrome c release
      from the mitochondria to the cytosol provided evidence that AM can induce
      apoptosis via mitochondrial-dependent pathway. AM exerted a remarkable antitumor
      effect and induced characteristic apoptogenic morphological changes on HeLa
      cells, which indicates the occurrence of cell death. This study reveals that AM
      could be a potential antitumor compound on cervical cancer in vitro and can be
      considered for further cervical cancer preclinical and in vivo testing.

PMID- 28740748
TI  - A highly pathogenic porcine reproductive and respiratory syndrome virus candidate
      vaccine based on Japanese encephalitis virus replicon system.
AB  - In the swine industry, porcine reproductive and respiratory syndrome (PRRS) is a
      highly contagious disease which causes heavy economic losses worldwide. Effective
      prevention and disease control is an important issue. In this study, we described
      the construction of a Japanese encephalitis virus (JEV) DNA-based replicon with a
      cytomegalovirus (CMV) promoter based on the genome of Japanese encephalitis live
      vaccine virus SA14-14-2, which is capable of offering a potentially novel way to
      develop and produce vaccines against a major pathogen of global health. This JEV
      DNA-based replicon contains a large deletion in the structural genes (C-prM-E). A
      PRRSV GP5/M was inserted into the deletion position of JEV DNA-based replicons to
      develop a chimeric replicon vaccine candidate for PRRSV. The results showed that
      BALB/c mice models with the replicon vaccines pJEV-REP-G-2A-M-IRES and pJEV-REP-G
      2A-M stimulated antibody responses and induced a cellular immune response.
      Analysis of ELSA data showed that vaccination with the replicon vaccine
      expressing GP5/M induced a better antibodies response than traditional DNA
      vaccines. Therefore, the results suggested that this ectopic expression system
      based on JEV DNA-based replicons may represent a useful molecular platform for
      various biological applications, and the JEV DNA-based replicons expressing GP5/M
      can be further developed into a novel, safe vaccine candidate for PRRS.

PMID- 28740749
TI  - A longitudinal study of the diabetic skin and wound microbiome.
AB  - BACKGROUND: Type II diabetes is a chronic health condition which is associated
      with skin conditions including chronic foot ulcers and an increased incidence of
      skin infections. The skin microbiome is thought to play important roles in skin
      defence and immune functioning. Diabetes affects the skin environment, and this
      may perturb skin microbiome with possible implications for skin infections and
      wound healing. This study examines the skin and wound microbiome in type II
      diabetes. METHODS: Eight type II diabetic subjects with chronic foot ulcers were
      followed over a time course of 10 weeks, sampling from both foot skin (swabs) and
      wounds (swabs and debrided tissue) every two weeks. A control group of eight
      control subjects was also followed over 10 weeks, and skin swabs collected from
      the foot skin every two weeks. Samples were processed for DNA and subject to 16S
      rRNA gene PCR and sequencing of the V4 region. RESULTS: The diabetic skin
      microbiome was significantly less diverse than control skin. Community
      composition was also significantly different between diabetic and control skin,
      however the most abundant taxa were similar between groups, with differences
      driven by very low abundant members of the skin communities. Chronic wounds
      tended to be dominated by the most abundant skin Staphylococcus, while other
      abundant wound taxa differed by patient. No significant correlations were found
      between wound duration or healing status and the abundance of any particular
      taxa. DISCUSSION: The major difference observed in this study of the skin
      microbiome associated with diabetes was a significant reduction in diversity. The
      long-term effects of reduced diversity are not yet well understood, but are often
      associated with disease conditions.

PMID- 28740750
TI  - Herbicide injury induces DNA methylome alterations in Arabidopsis.
AB  - The emergence of herbicide-resistant weeds is a major threat facing modern
      agriculture. Over 470 weedy-plant populations have developed resistance to
      herbicides. Traditional evolutionary mechanisms are not always sufficient to
      explain the rapidity with which certain weed populations adapt in response to
      herbicide exposure. Stress-induced epigenetic changes, such as alterations in DNA
      methylation, are potential additional adaptive mechanisms for herbicide
      resistance. We performed methylC sequencing of Arabidopsis thaliana leaves that
      developed after either mock treatment or two different sub-lethal doses of the
      herbicide glyphosate, the most-used herbicide in the history of agriculture. The
      herbicide injury resulted in 9,205 differentially methylated regions (DMRs)
      across the genome. In total, 5,914 of these DMRs were induced in a dose-dependent
      manner, wherein the methylation levels were positively correlated to the severity
      of the herbicide injury, suggesting that plants can modulate the magnitude of
      methylation changes based on the severity of the stress. Of the 3,680 genes
      associated with glyphosate-induced DMRs, only 7% were also implicated in
      methylation changes following biotic or salinity stress. These results
      demonstrate that plants respond to herbicide stress through changes in
      methylation patterns that are, in general, dose-sensitive and, at least
      partially, stress-specific.

PMID- 28740751
TI  - DAPK1 as an independent prognostic marker in liver cancer.
AB  - The death-associated protein kinase 1 (DAPK1) can act as an oncogene or a tumor
      suppressor gene depending on the cellular context as well as external stimuli.
      Our study aims to investigate the prognostic significance of DAPK1 in liver
      cancer in both mRNA and protein levels. The mRNA expression of DAPK1 was
      extracted from the Gene Expression Omnibus database in three independent liver
      cancer datasets while protein expression of DAPK1 was detected by
      immunohistochemistry in our Chinese liver cancer patient cohort. The associations
      between DAPK1 expression and clinical characteristics were tested. DAPK1 mRNA
      expression was down-regulated in liver cancer. Low levels of DAPK1 mRNA were
      associated with shorter survival in a liver cancer patient cohort (n = 115; p =
      0.041), while negative staining of DAPK1 protein was significantly correlated
      with shorter time to progression (p = 0.002) and overall survival (p = 0.02).
      DAPK1 was an independent prognostic marker for both time to progression and
      overall survival by multivariate analysis. Liver cancer with the b-catenin
      mutation has a lower DAPK1 expression, suggesting that DAPK1 may be regulated
      under the b-catenin pathway. In addition, we also identified genes that are co
      regulated with DAPK1. DAPK1 expression was positively correlated with IRF2, IL7R,
      PCOLCE and ZBTB16, and negatively correlated with SLC16A3 in both liver cancer
      datasets. Among these genes, PCOLCE and ZBTB16 were significantly down-regulated,
      while SLC16A3 was significantly upregulated in liver cancer. By using
      connectivity mapping of these co-regulated genes, we have identified amcinonide
      and sulpiride as potential small molecules that could potentially reverse
      DAPK1/PCOLCE/ZBTB16/SLC16A3 expression. Our study demonstrated for the first time
      that both DAPK1 mRNA and protein expression levels are important prognostic
      markers in liver cancer, and have identified genes that may contribute to DAPK1
      mediated liver carcinogenesis.

PMID- 28740752
TI  - Long-term resource addition to a detrital food web yields a pattern of responses
      more complex than pervasive bottom-up control.
AB  - BACKGROUND: Theory predicts strong bottom-up control in detritus-based food webs,
      yet field experiments with detritus-based terrestrial systems have uncovered
      contradictory evidence regarding the strength and pervasiveness of bottom-up
      control processes. Two factors likely leading to contradictory results are
      experiment duration, which influences exposure to temporal variation in abiotic
      factors such as rainfall and affects the likelihood of detecting approach to a
      new equilibrium; and openness of the experimental units to immigration and
      emigration. To investigate the contribution of these two factors, we conducted a
      long-term experiment with open and fenced plots in the forest that was the site
      of an earlier, short-term experiment (3.5 months) with open plots (Chen & Wise,
      1999) that produced evidence of strong bottom-up control for 14 taxonomic
      groupings of primary consumers of fungi and detritus (microbi-detritivores) and
      their predators. METHODS: We added artificial high-quality detritus to ten 2 * 2
      m forest-floor plots at bi-weekly intervals from April through September in three
      consecutive years (Supplemented treatment). Ten comparable Ambient plots were
      controls. Half of the Supplemented and Ambient plots were enclosed by metal
      fencing. RESULTS: Arthropod community structure (based upon 18 response
      variables) diverged over time between Supplemented and Ambient treatments, with
      no effect of Fencing on the multivariate response pattern. Fencing possibly
      influenced only ca. 30% of the subsequent univariate analyses. Multi- and
      univariate analyses revealed bottom-up control during Year 1 of some, but not
      all, microbi-detritivores and predators. During the following two years the
      pattern of responses became more complex than that observed by Chen & Wise
      (1999). Some taxa showed consistent bottom-up control whereas others did not.
      Variation across years could not be explained completely by differences in
      rainfall because some taxa exhibited negative, not positive, responses to
      detrital supplementation. DISCUSSION: Our 3-year experiment did not confirm the
      conclusion of strong, pervasive bottom-up control of both microbi-detritivores
      and predators reported by Chen & Wise (1999). Our longer-term experiment revealed
      a more complex pattern of responses, a pattern much closer to the range of
      outcomes reported in the literature for many short-term experiments. Much of the
      variation in responses across studies likely reflects variation in abiotic and
      biotic factors and the quality of added detritus. Nevertheless, it is also
      possible that long-term resource enhancement can drive a community towards a new
      equilibrium state that differs from what would have been predicted from the
      initial short-term responses exhibited by primary and secondary consumers.

PMID- 28740753
TI  - A laid-back trip through the Hennigian Forests.
AB  - BACKGROUND: This paper is a comment on the idea of matrix-free Cladistics.
      Demonstration of this idea's efficiency is a major goal of the study. Within the
      proposed framework, the ordinary (phenetic) matrix is necessary only as "source"
      of Hennigian trees, not as a primary subject of the analysis. Switching from the
      matrix-based thinking to the matrix-free Cladistic approach clearly reveals that
      optimizations of the character-state changes are related not to the real
      processes, but to the form of the data representation. METHODS: We focused our
      study on the binary data. We wrote the simple ruby-based script FORESTER version
      1.0 that helps represent a binary matrix as an array of the rooted trees (as a
      "Hennigian forest"). The binary representations of the genomic (DNA) data have
      been made by script 1001. The Average Consensus method as well as the standard
      Maximum Parsimony (MP) approach has been used to analyze the data. PRINCIPLE
      FINDINGS: The binary matrix may be easily re-written as a set of rooted trees
      (maximal relationships). The latter might be analyzed by the Average Consensus
      method. Paradoxically, this method, if applied to the Hennigian forests, in
      principle can help to identify clades despite the absence of the direct evidence
      from the primary data. Our approach may handle the clock- or non clock-like
      matrices, as well as the hypothetical, molecular or morphological data.
      DISCUSSION: Our proposal clearly differs from the numerous phenetic alignment
      free techniques of the construction of the phylogenetic trees. Dealing with the
      relations, not with the actual "data" also distinguishes our approach from all
      optimization-based methods, if the optimization is defined as a way to
      reconstruct the sequences of the character-state changes on a tree, either the
      standard alignment-based techniques or the "direct" alignment-free procedure. We
      are not viewing our recent framework as an alternative to the three-taxon
      statement analysis (3TA), but there are two major differences between our recent
      proposal and the 3TA, as originally designed and implemented: (1) the 3TA deals
      with the three-taxon statements or minimal relationships. According to the logic
      of 3TA, the set of the minimal trees must be established as a binary matrix and
      used as an input for the parsimony program. In this paper, we operate directly
      with maximal relationships written just as trees, not as binary matrices, while
      also using the Average Consensus method instead of the MP analysis. The solely
      'reversal'-based groups can always be found by our method without the separate
      scoring of the putative reversals before analyses.

PMID- 28740754
TI  - The time-course of broiler intestinal microbiota development after administration
      of cecal contents to incubating eggs.
AB  - BACKGROUND: The microbial populations that inhabit the gastrointestinal tract
      (GIT) are known to influence the health and growth performance of the host. Clean
      hatcheries and machine-based incubation practices in the commercial poultry
      industry can lead to the acquisition of aberrant microbiota in the GIT of
      chickens and a very high level of bird-to-bird variation. The lack of microbial
      profile flock uniformity presents challenges for harnessing and manipulating
      intestinal bacteria to better serve the host. METHODS: Cecal contents from high
      or low performing chickens were used to inoculate the surface of eggs prior to
      hatching and then the initial gut colonisation was monitored and subsequent
      changes in gut microbiota composition were followed over time. Two different
      cecal treatment groups were compared to an untreated control group (n = 32).
      Bacterial communities were characterised using high-throughput 16S rRNA gene
      sequencing techniques. RESULTS: Cecal microbiota transfer via egg surface
      application did not transfer the performance profile of the donors to the
      recipient birds. One of the cecal inoculations provided a more uniform gut
      microbiota, but this was not reproduced in the second group with a different
      inoculum. Development of the intestinal community was reproducible in all three
      groups with some genera like Lactobacillus showing no change, others like
      Faecalibacterium increased in abundance slowly and steadily over time and others
      like Enterobacter were abundant only in the first days of life. DISCUSSION: The
      cecal treatment reduced bird-to-bird variation in microbiota composition.
      Although the high FCR performance of donor birds was not transferred with the
      cecal microbiota, all three groups, including the control, performed better than
      standard for the breed. The pattern of microbiota development was similar in all
      three flocks, indicating that the normal processes of microbiota acquisition
      largely swamped any effect of the cecal material applied to eggs.

PMID- 28740755
TI  - Identifying genes and regulatory pathways associated with the scleractinian coral
      calcification process.
AB  - Reef building corals precipitate calcium carbonate as an exo-skeleton and provide
      substratum for prosperous marine life. Biomineralization of the coral's skeleton
      is a developmental process that occurs concurrently with other proliferation
      processes that control the animal extension and growth. The development of the
      animal body is regulated by large gene regulatory networks, which control the
      expression of gene sets that progressively generate developmental patterns in the
      animal body. In this study we have explored the gene expression profile and
      signaling pathways followed by the calcification process of a basal metazoan, the
      Red Sea scleractinian (stony) coral, Stylophora pistillata. When treated by
      seawater with high calcium concentrations (addition of 100 gm/L, added as
      CaCl2.2H2O), the coral increases its calcification rates and associated genes
      were up-regulated as a result, which were then identified. Gene expression was
      compared between corals treated with elevated and normal calcium concentrations.
      Calcification rate measurements and gene expression analysis by microarray RNA
      transcriptional profiling at two time-points (midday and night-time) revealed
      several genes common within mammalian gene regulatory networks. This study
      indicates that core genes of the Wnt and TGF-beta/BMP signaling pathways may also
      play roles in development, growth, and biomineralization in early-diverging
      organisms such as corals.

PMID- 28740756
TI  - Sonographic evaluation of the immediate effects of eccentric heel drop exercise
      on Achilles tendon and gastrocnemius muscle stiffness using shear wave
      elastography.
AB  - BACKGROUND: Mechanical loading is crucial for muscle and tendon tissue
      remodeling. Eccentric heel drop exercise has been proven to be effective in the
      management of Achilles tendinopathy, yet its induced change in the mechanical
      property (i.e., stiffness) of the Achilles tendon (AT), medial and lateral
      gastrocnemius muscles (MG and LG) was unknown. Given that shear wave elastography
      has emerged as a powerful tool in assessing soft tissue stiffness with promising
      intra- and inter-operator reliability, the objective of this study was hence to
      characterize the stiffness of the AT, MG and LG in response to an acute bout of
      eccentric heel drop exercise. METHODS: Forty-five healthy young adults (36 males
      and nine females) performed 10 sets of 15-repetition heel drop exercise on their
      dominant leg with fully-extended knee, during which the AT and gastrocnemius
      muscles, but not soleus, were highly stretched. Before and immediately after the
      heel drop exercise, elastic moduli of the AT, MG and LG were measured by shear
      wave elastography. RESULTS: After the heel drop exercise, the stiffness of AT
      increased significantly by 41.8 + 33.5% (P < 0.001), whereas the increases in the
      MG and LG stiffness were found to be more drastic by 75 + 47.7% (P < 0.001) and
      71.7 + 51.8% (P < 0.001), respectively. Regarding the AT, MG and LG stiffness
      measurements, the inter-operator reliability was 0.940, 0.987 and 0.986, and the
      intra-operator reliability was 0.916 to 0.978, 0.801 to 0.961 and 0.889 to 0.985,
      respectively. DISCUSSION: The gastrocnemius muscles were shown to bear larger
      mechanical loads than the AT during an acute bout of eccentric heel drop
      exercise. The findings from this pilot study shed some light on how and to what
      extent the AT and gastrocnemius muscles mechanically responds to an isolated set
      of heel drop exercise. Taken together, appropriate eccentric load might
      potentially benefit mechanical adaptations of the AT and gastrocnemius muscles in
      the rehabilitation of patients with Achilles tendinopathy.

PMID- 28740757
TI  - Using electroretinograms and multi-model inference to identify spectral classes
      of photoreceptors and relative opsin expression levels.
AB  - Understanding how individual photoreceptor cells factor in the spectral
      sensitivity of a visual system is essential to explain how they contribute to the
      visual ecology of the animal in question. Existing methods that model the
      absorption of visual pigments use templates which correspond closely to data from
      thin cross-sections of photoreceptor cells. However, few modeling approaches use
      a single framework to incorporate physical parameters of real photoreceptors,
      which can be fused, and can form vertical tiers. Akaike's information criterion
      (AICc) was used here to select absorptance models of multiple classes of
      photoreceptor cells that maximize information, given visual system spectral
      sensitivity data obtained using extracellular electroretinograms and structural
      parameters obtained by histological methods. This framework was first used to
      select among alternative hypotheses of photoreceptor number. It identified
      spectral classes from a range of dark-adapted visual systems which have between
      one and four spectral photoreceptor classes. These were the velvet worm,
      Principapillatus hitoyensis, the branchiopod water flea, Daphnia magna, normal
      humans, and humans with enhanced S-cone syndrome, a condition in which S-cone
      frequency is increased due to mutations in a transcription factor that controls
      photoreceptor expression. Data from the Asian swallowtail, Papilio xuthus, which
      has at least five main spectral photoreceptor classes in its compound eyes, were
      included to illustrate potential effects of model over-simplification on multi
      model inference. The multi-model framework was then used with parameters of
      spectral photoreceptor classes and the structural photoreceptor array kept
      constant. The goal was to map relative opsin expression to visual pigment
      concentration. It identified relative opsin expression differences for two
      populations of the bluefin killifish, Lucania goodei. The modeling approach
      presented here will be useful in selecting the most likely alternative hypotheses
      of opsin-based spectral photoreceptor classes, using relative opsin expression
      and extracellular electroretinography.

PMID- 28740758
TI  - Identification and characterization of Streptomyces flavogriseus NJ-4 as a novel
      producer of actinomycin D and holomycin.
AB  - This paper is the first public report that Streptomyces flavogriseus can produce
      both actinomycin D and holomycin. The actinomycete strain NJ-4 isolated from the
      soil of Nanjing Agricultural University was identified as S. flavogriseus. This
      S. flavogriseus strain was found for the first time to produce two antimicrobial
      compounds that were identified as actinomycin D and holomycin. GS medium, CS
      medium and GSS medium were used for the production experiments. All three media
      supported the production of actinomycin D, while holomycin was detected only in
      GS medium and was undetectable by HPLC in the CS and GSS media. The antimicrobial
      activity against B. pumilus, S. aureus, Escherichia coli, F. moniliforme, F.
      graminearum and A. niger was tested using the agar well diffusion method.
      Actinomycin D exhibited strong antagonistic activities against all the indicator
      strains. Holomycin exhibited strong antagonistic activities against B. pumilus,
      S. aureus and E. coli and had antifungal activity against F. moniliforme and F.
      graminearum but had no antifungal activity against A. niger. The cell viability
      was determined using an MTT assay. Holomycin exhibited cytotoxic activity against
      A549 lung cancer cells, BGC823 gastric cancer cells and HepG2 hepatocellular
      carcinoma cells. The yield of actinomycin D from S. flavogriseus NJ-4 was 960
      mg/l. S. flavogriseus NJ-4 exhibits a distinct capability and has the industrial
      potential to produce considerable yields of actinomycin D under unoptimized
      conditions.

PMID- 28740759
TI  - A positive readout single transcript reporter for site-specific mRNA cleavage.
AB  - Cleavage of mRNA molecules causes their rapid degradation, thereby playing an
      important role in regulation of gene expression and host genome defense from
      viruses and transposons in bacterial and eukaryotic cells. Current negative
      readout, and repressor-based positive-readout reporters of mRNA degradation have
      limitations. Here we report the development of a single transcript that acts as a
      positive reporter of mRNA cleavage. We show that placement of bacterial CopT and
      CopA hairpins into the 5' UTR and 3' UTR of an mRNA results in inhibition of
      translation of the intervening coding sequence in Drosophila. An internal poly(A)
      tract inserted downstream of the coding sequence stabilizes transcripts cut
      within the 3' UTR. When these components are combined in a transcript in which
      targets sites for RNA cleavage are placed between the poly(A) tract and CopA,
      cleavage results in translational activation, providing a single transcript-based
      method of sensing mRNA cleavage with a positive readout.

PMID- 28740760
TI  - Leaf arrangements are invalid in the taxonomy of orchid species.
AB  - The selection and validation of proper distinguishing characters are of crucial
      importance in taxonomic revisions. The modern classifications of orchids utilize
      the molecular tools, but still the selection and identification of the material
      used in these studies is for the most part related to general species morphology.
      One of the vegetative characters quoted in orchid manuals is leaf arrangement.
      However, phyllotactic diversity and ontogenetic changeability have not been
      analysed in detail in reference to particular taxonomic groups. Therefore, we
      evaluated the usefulness of leaf arrangements in the taxonomy of the genus
      Epipactis Zinn, 1757. Typical leaf arrangements in shoots of this genus are
      described as distichous or spiral. However, in the course of field research and
      screening of herbarium materials, we indisputably disproved the presence of
      distichous phyllotaxis in the species Epipactis purpurata Sm. and confirmed the
      spiral Fibonacci pattern as the dominant leaf arrangement. In addition, detailed
      analyses revealed the presence of atypical decussate phyllotaxis in this species,
      as well as demonstrated the ontogenetic formation of pseudowhorls. These findings
      confirm ontogenetic variability and plasticity in E. purpurata. Our results are
      discussed in the context of their significance in delimitations of complex taxa
      within the genus Epipactis.

PMID- 28740761
TI  - Local Application of Statins Significantly Reduced Hypertrophic Scarring in a
      Rabbit Ear Model.
AB  - BACKGROUND: We previously showed that intradermal injection of statins is a
      successful treatment for hypertrophic scarring. Topical application has many
      advantages over intradermal injection. In this study, we demonstrate the efficacy
      of topical statin treatment in reducing scar in our validated rabbit ear scar
      model. METHODS: Twenty New Zealand White rabbits were divided into 2 study
      groups, with 6 rabbits receiving 10 MUm pravastatin intradermally at
      postoperative days 15, 18, and 21, and 14 rabbits receiving 0.4%, 2%, and 10%
      simvastatin topical application at postoperative days 14-25. Four or 6 full
      thickness circular dermal punches 7 mm in diameter were made on the ventral
      surface of the ear down to but not including the perichondrium. Specimens were
      collected at 28 days to evaluate the effects of statins on hypertrophic scarring.
      RESULTS: Treatment with pravastatin intradermal administration significantly
      reduced scarring in terms of scar elevation index. Topical treatment with both
      medium- and high-dose simvastatin also significantly reduced scarring. High-dose
      simvastatin topical treatment showed a major effect in scar reduction but induced
      side effects of scaling, erythema, and epidermal hyperplasia, which were improved
      with coapplication of cholesterol. There is a dose response in scar reduction
      with low-, medium- and high-dose simvastatin topical treatment. High-dose
      simvastatin treatment significantly reduced the messenger ribonucleic acid (mRNA)
      expression of connective tissue growth factor, consistent with our previously
      published work on intradermally injected statins. More directly, high-dose
      simvastatin treatment also significantly reduced the mRNA expression of collagen
      1A1. CONCLUSIONS: Topical simvastatin significantly reduces scar formation. The
      mechanism of efficacy for statin treatment through interference with connective
      tissue growth factor mRNA expression was confirmed.

PMID- 28740762
TI  - Long-Term Health-Related Quality of Life after Breast Reconstruction: Comparing 4
      Different Methods of Reconstruction.
AB  - BACKGROUND: Studies have confirmed that breast reconstruction is beneficial to
      improve health-related quality of life (HR-QoL) in breast cancer patients. Our
      aim was to compare 4 different methods of breast reconstruction on patient
      satisfaction and HR-QoL using both general and specific patient-reported outcome
      instruments. METHODS: Retrospectively, 459 patients who underwent breast
      reconstruction with a deep inferior epigastric artery perforator (DIEP) flap,
      latissimus dorsi flap, lateral thoracodorsal flap, or expander with secondary
      implant and who had responded to the questionnaires were enrolled. Questionnaire
      answers, together with demographic and follow-up data, were statistically
      analyzed and compared between groups. Short-Form 36 Health Survey (SF-36) results
      were also compared with those from a sample of 930 age-matched women from the
      Swedish population. RESULTS: There were slight differences in the SF-36 results
      but no significant differences in Psychological General Well-Being Index and
      EuroQoL-5 Dimension Questionnaire results between groups. Analysis of Breast-Q
      showed that the DIEP group had significantly higher score on the scale
      satisfaction with breast, significantly higher score in satisfaction with outcome
      than the lateral thoracodorsal flap (P = 0.014) and EXP groups (P = 0.024). There
      were no significant differences in most of the domains of the HR-QoL instruments.
      The higher satisfaction with breasts and outcome in the DIEP group is
      interesting, considering the higher complication rates associated with this
      reconstruction method. CONCLUSIONS: Patients who underwent breast reconstruction
      with a DIEP flap were more satisfied with their reconstructed breast and outcome
      than the other 3 groups. Breast reconstruction centers should make DIEP
      reconstruction widely available to patients after mastectomy.

PMID- 28740763
TI  - Lymphaticovenous Bypass: Adaptations and Lessons Learned.
AB  - Advances in microsurgical instruments and techniques have allowed for
      introduction of lymphaticovenous anastomosis as a potential surgical treatment
      for patients with upper and lower extremity lymphedema. This article reviews the
      approach to lymphaticovenous anastomosis patient selection and technical
      modifications that improve the ease and efficiency of the procedure.

PMID- 28740764
TI  - Multiple Free Flap Reconstructions of Head and Neck Defects Due to Oral Cancer.
AB  - OBJECTIVE: We studied complications following multiple free flap reconstructions
      in the head and neck. METHODS: In this cohort, 26 patients (14 men and 12 women)
      who underwent multiple microvascular free flap reconstructions were included in
      the study. The reasons for secondary reconstruction were recurrence of tumor (12
      cases), necrosis of transferred skin and/or bone (6 cases), reconstruction plate
      fracture or exposure (4 cases), and others (4 cases). A third reconstruction in 4
      cases and a fourth reconstruction in 1 case were performed. RESULTS: No flap
      necrosis occurred. Postsurgical infections occurred at only secondary
      reconstructions in 7 patients. Although 4 cases with a history of external
      radiation therapy were anastomosed at contralateral side, those 4 cases suffered
      from severe pre-and postsurgical infection of the ipsilateral side. Postsurgical
      infection occurred in 2 cases with anastomoses at the ipsilateral side of the
      neck and required drainage after secondary surgery. CONCLUSIONS: A history of
      external radiation therapy and the existence of severe preoperative infection
      affected complications after multiple reconstructions.

PMID- 28740765
TI  - Lipoabdominoplasty with Progressive Traction Sutures.
AB  - BACKGROUND: Proactively preserving Scarpa's fascia and thus its intrinsic
      lymphatic drainage and tensile strength for suture placement can eliminate the
      need for drains after lipoabdominoplasty and therefore reduce the rate of seroma
      development. In this article, we describe the effectiveness of a modified
      progressive traction suture (PTS) technique, which enables us to lessen the most
      common complications and avoid hospital readmission; these sutures take 3-5
      minutes of additional surgery time. METHODS: Two hundred seventy-six patients
      (mean age, 38 years; range, 19-67 years), with a mean body mass index of 25 were
      included in this study. All patients underwent complete lipoabdominoplasty with
      ultrasound-assisted liposuction (VASER) throughout the abdomen and flanks.
      Abdominal rectus plication was performed in 100% of cases. All patients were
      operated on under spinal anesthesia and stayed overnight in hospital. RESULTS: Of
      the 276 patients, 1.8% developed postoperative seromas. No patients developed
      hematomas. New wound closure was needed in 1.4% of patients, performed within 7
      10 days of surgery, scar revision in 4.7%, residual liposuction under local
      anesthesia in 9.7%, and liposuction under sedation in 1%; deep vein thrombosis
      without thromboembolic phenomenon developed in 1%, none resulting in death. In
      addition, the use of a PTS technique is a time-saving procedure because it takes
      the surgeons between 3-5 minutes of operative time, unlike that of adhesion
      and/or separate traction, which takes between 30 and 45 minutes. CONCLUSIONS: The
      use of PTSs helped diminish complications such as seroma and hematoma and prevent
      additional cost involving hospital readmission and/or further surgery.
      Furthermore, use of these sutures required only 3-5 minutes of additional
      operative time.

PMID- 28740766
TI  - Early Cleft Lip Repair Revisited: A Safe and Effective Approach Utilizing a
      Multidisciplinary Protocol.
AB  - BACKGROUND: The optimal timing for cleft lip repair has yet to be established.
      Advances in neonatal anesthesia, along with a growing body of literature,
      suggesting benefits of earlier cleft lip and nasal repair, have set the stage for
      a reexamination of current practices. METHODS: In this prospective study, cleft
      lip and nasal repair occurred on average at 34.8 days (13-69 days). Nasal
      correction was achieved primarily through molding the nasal cartilage without the
      placement of nasal sutures at the time of repair. A standardized anesthetic
      protocol aimed at limiting neurotoxicity was utilized in all cases. Anesthetic
      and postoperative complications were assessed. A 3-dimensional nasal analysis
      compared pre- and postoperative nasal symmetry for unilateral clefts. Surveys
      assessed familial response to repair. RESULTS: Thirty-two patients were included
      (27 unilateral and 5 bilateral clefts). In this study, the overall complication
      rate was 3.1%. Anthropometric measurements taken from 3-dimensional-image models
      showed statistically significant improvement in ratios of nostril height
      (preoperative mean, 0.59; postoperative mean, 0.80), nasal base width
      (preoperative mean, 1.96; postoperative mean, 1.12), columella length
      (preoperative mean, 0.62; postoperative mean, 0.89; and columella angle
      (preoperative mean, 30.73; postoperative mean, 9.1). Survey data indicated that
      families uniformly preferred earlier repair. CONCLUSIONS: We present evidence
      that early cleft lip and nasal repair can be performed safely and is effective at
      improving nasal symmetry without the placement of any nasal sutures. Utilization
      of this protocol has the potential to be a paradigm shift in the treatment of
      cleft lip and nasal deformity.

PMID- 28740767
TI  - The Effect of the Timing of Radiotherapy on Clinical and Patient-Reported
      Outcomes After Latissimus Dorsi Breast Reconstruction: A 10-Year Study.
AB  - BACKGROUND: Breast reconstruction (BR) is considered to be adversely affected by
      radiotherapy (RT), particularly when an implant is used. The aim of this study
      was to compare clinical and patient-reported outcomes after expander-assisted
      latissimus dorsi breast reconstruction depending on the timing of RT. METHODS:
      Patients undergoing BR over a 10-year period (follow-up mean, 56 [14-134] months)
      were divided into 3 groups. Group 1, RT after mastectomy and BR, Group 2, RT
      before mastectomy and BR, and Group 3, RT after mastectomy but before BR. The
      primary endpoints were early and late surgical interventions. Validated
      questionnaires were circulated to all study patients and matched controls.
      RESULTS: Three hundred thirteen patients underwent 389 BRs. One hundred eighteen
      patients received RT, of which 65 had undergone expander-assisted latissimus
      dorsi breast reconstruction. Both use and timing of RT influenced clinical
      outcomes. Overall, use of RT resulted in a 3-fold increase in complications (P =
      0.003). Postreconstruction RT resulted in more than double the number of
      complications compared with prereconstruction RT (P = 0.008) and delaying BR
      until after mastectomy and RT reduced complications to levels observed in control
      patients (P = nonsignificant). Complications were halved in patients undergoing
      autologous LD reconstruction (P = 0.0001). Patient-reported outcomes were similar
      for emotional well-being, satisfaction, and shoulder symptoms, although a
      nonsignificant increase in chronic breast symptoms was reported by the RT group.
      CONCLUSION: The timing and type of LD reconstruction chosen by patients receiving
      RT has a significant impact on the risk of subsequent complications and unplanned
      interventions but has little impact on longer term patient well-being or
      satisfaction.

PMID- 28740768
TI  - fMRI after Phalloplasty with Nerve Anastomosis in a Trans-Man Patient.
AB  - We report on a case of a trans-man patient, who underwent penile reconstruction
      with the use of a radial forearm flap, urethroplasty, vaginectomy and
      scrotoplasty, insertion of testicle implants, and penile erection implants,
      similar to previously described methods. One of the requirements for an ideal
      phalloplasty is the preservation of erogenous sensitivity, which is often
      demanded by the patients for fulfilling their sexual well-being. For the first
      time known to us, we use a functional magnetic resonance imaging following radial
      forearm flap phalloplasty with nerve anastomosis to assess the cortical
      activation after clitoral stimulation. The patient was poked with a plastic pen
      on the neophallus and the groin. Regular block design with T1 and BOLD-T2* images
      were used. The results contradict the classic Penfield and Rasmussen homunculus,
      that is, the activations in the primary somatosensory cortex (S1) were bilateral
      with a left-sided dominance in the lateral parts of the medial postcentral gyrus
      (same region as the groin), and no activations were observed in the mesial parts
      of the postcentral gyrus. We also reported bilateral activations with a left
      sided dominance in the secondary somatosensory cortex (S2) and near Broca's area
      at the sylvian fissure just posterior to ramus ascendens. Our findings are
      similar to previous studies reporting on imaging related to genital sensitivity.

PMID- 28740769
TI  - Simply Do Not Go Snowboarding 2 Weeks after Augmentation.

PMID- 28740770
TI  - Versatility of the Latissimus Dorsi Free Flap during the Treatment of Complex
      Postcraniotomy Surgical Site Infections.
AB  - BACKGROUND: Some intractable cases of postcraniotomy infection, which can involve
      compromised skin, an open frontal air sinus, and residual epidural dead space,
      have been reported. In such cases, reconstructing the scalp and skull is
      challenging. METHODS: Between 2009 and 2016, the author treated 12 patients with
      recalcitrant postcraniotomy surgical site infections with latissimus dorsi (LD)
      free flaps. The patients' ages ranged from 37 to 79 years (mean, 63.5 years), and
      their underlying diseases included subarachnoid hemorrhaging (n = 5), brain
      tumors (n = 4), and cerebral arteriovenous malformations (n = 3). RESULTS: The LD
      free flap was used for scalp reconstruction in 3 cases, scalp reconstruction and
      separation of the intracranial and nasal cavities in 5 cases, and the
      obliteration of epidural dead space in 4 cases. Debridement followed by staged
      cranial reconstruction was carried out in 8 cases, and single-stage cranial
      reconstruction was conducted in 2 cases. The bone defects of the other 2 cases,
      which were small, were filled with LD musculo-adipose free flaps. The
      postoperative local appearance of the wounds was acceptable in every case, and no
      complications occurred. CONCLUSIONS: The LD free flap is a versatile tool for the
      treatment of complex postcraniotomy surgical site infections. This vascularized
      muscle flap is useful for controlling local infections because of its abundant
      vascularity. Moreover, its variety of uses means that it can resolve several
      problems in cases involving complex cranial wounds.

PMID- 28740771
TI  - Venous Thromboembolism Risk Stratification and Chemoprophylaxis: A Meta-Analysis
      Finds No Benefit, More Risk.

PMID- 28740772
TI  - Relationship between Keloid Formation and YAP/TAZ Signaling.
AB  - YAP (yes-associated protein) and TAZ (transcriptional coactivator with PDZ
      binding motif) are part of a classical pathway that controls contact inhibition
      in the Hippo pathway. YAP and TAZ were recently reported to act as nuclear relays
      of mechanical signals that communicate extracellular matrix rigidity and cell
      shape. However, the role of YAP/TAZ signaling in keloid formation is unclear.
      Here, we used immunohistochemistry to investigate YAP/TAZ expression in keloid
      and nonaffected lesions. YAP/TAZ expression in keloid fibroblasts had a greater
      tendency to localize to the nucleus relative to that seen in fibroblasts from
      unaffected tissues. Meanwhile, keratinocytes or endothelial cells from either
      keloid or unaffected tissues showed no significant differences in YAP/TAZ
      expression patterns. These results suggest that YAP/TAZ nuclear localization in
      keloid fibroblasts might activate Hippo signaling and may play an important role
      in gene expression that affects keloid formation and stiffness.

PMID- 28740773
TI  - Botulinum Toxin A as an Adjunct to Abdominal Wall Reconstruction for Incisional
      Hernia.
AB  - BACKGROUND: Repair of large incisional hernias remains a surgical and costly
      challenge. Temporary paralysis of the lateral abdominal wall muscles with topical
      administration of botulinum toxin A (BTA) is a new therapeutic concept, which may
      obviate the need for component separation technique (CST) for repair of large
      incisional hernias. Current literature on the administration of BTA as adjunct to
      surgical repair of abdominal incisional hernias was investigated. METHODS: The
      electronic databases PubMed and Embase were searched for eligible studies. Two
      independent investigators evaluated the literature. Data were sought regarding
      primary fascial closure with and without CST, safety, hernia recurrence, method
      of application, and preoperative radiological imaging. RESULTS: Six cohort
      studies including a total of 133 patients receiving BTA were identified. No
      randomized or case-control studies were found. In total, 83.5% of the patients
      achieved primary fascial closure. Supplemental CST was necessary in 24.1% of the
      patients. Two patients developed hernia recurrence during follow-up. No
      postoperative complications or adverse events were considered related to the
      administration of BTA, except for impairment of postoperative coughing and
      sneezing. Additionally, radiological imaging showed that BTA increased the length
      of lateral abdominal muscles before surgery. CONCLUSIONS: Preoperative
      administration of BTA increases muscle length and may facilitate primary fascial
      closure. Optimal administration is at least 2 weeks before repair, whereas the
      optimal dose of BTA remains to be defined. Carefully designed randomized
      controlled trials are warranted to identify patients who would benefit from BTA
      and to eliminate the confounding effect of CST.

PMID- 28740774
TI  - Unilateral Internal Mammary Recipient Vessels for Bilateral DIEP Flap Breast
      Reconstruction.
AB  - The deep inferior epigastric perforator flap has become increasingly popular for
      breast reconstruction with the most common recipient vessels being the internal
      mammary artery and vein. In certain cases, however, these recipient vessels are
      inadequate due to an absent or diminutive vein. Moreover, patients at high risk
      for future coronary artery disease may sacrifice the best conduit for coronary
      revascularization if the internal mammary recipients are used. Alternative
      recipient vessels, including the thoracodorsal, thoracoacromial, external
      jugular, and cephalic vessels have significant limitations. In this report, we
      describe a novel technique using unilateral internal mammary recipient vessels
      for bilateral free flap breast reconstruction. Two cases are presented that
      represent distinct indications for this technique: (1) absence or inadequacy of
      unilateral recipient vessels and (2) preservation of the left internal mammary
      system for future bypass in patients at high risk for coronary artery disease.

PMID- 28740775
TI  - Acute A4 Pulley Reconstruction with a First Extensor Compartment Onlay Graft.
AB  - BACKGROUND: The integrity of the flexor tendon pulley apparatus is crucial for
      unimpaired function of the digits. Although secondary reconstruction is an
      established procedure in multi-pulley injuries, acute reconstruction of isolated,
      closed pulley ruptures is a rare occurrence. There are 3 factors influencing the
      functional outcome of a reconstruction: gapping distance between tendon and bone
      (E-space), bulkiness of the reconstruction, and stability. As direct repair is
      rarely done, grafts are used to reinforce the pulley. An advantage of the first
      extensor retinaculum graft is the synovial coating providing the possibility to
      be used both as a direct graft with synovial coating or as an onlay graft after
      removal of the synovia when the native synovial layer is present. METHODS: A
      graft from the first dorsal extensor compartment is used as an onlay graft to
      reinforce the sutured A4 pulley. This technique allows reconstruction of the
      original dimensions of the pulley system while stability is ensured by anchoring
      the onlay graft to the bony insertions of the pulley. RESULTS: Anatomical
      reconstruction can be achieved with this method. The measured E-space remained 0
      mm throughout the recovery, while the graft incorporated as a slim reinforcement
      of the pulley, displaying no bulkiness. CONCLUSIONS: The ideal reconstruction
      should provide synovial coating and sufficient strength with minimal bulk. Early
      reconstruction using an onlay graft offers these options. The native synovial
      lining is preserved and the graft is used to reinforce the pulley.

PMID- 28740776
TI  - Tc-99m-Human Serum Albumin Transit Time as a Measure of Arm Breast Cancer-Related
      Lymphedema.
AB  - BACKGROUND: Lymphoscintigraphy has often been used for evaluating arm lymphatic
      dysfunction, but no optimal approach for quantification has so far emerged. We
      propose a quantifiable measure of lymphatic function that we applied in patients
      treated for breast cancer. METHODS: Eleven patients, aged 34-68 years, with
      unilateral arm lymphedema following breast cancer treatment underwent bilateral
      lymphoscintigraphy using intradermal injection in both hands of technetium-99m
      labeled human serum albumin and sequential 5 min imaging for 5 hours. The mean
      transit time (MTT) in the arms was calculated based on time activity curves
      generated from injection site and arm regions. Visual lymphedema scoring was
      performed based on dermal backflow and lymph node presence. Excess arm volume was
      calculated from circumference measurements. RESULTS: The MTT (mean +/- SD) was
      significantly longer in the lymphedema arm than in the normal arm: 60.1 +/- 27.7
      versus 5.4 +/- 2.5 minutes (mean difference, 54.7 minutes; 95% confidence
      interval, 36.5-72.9 minutes; P < 0.0001). Patients with previous erysipelas
      infection had significantly longer MTT than other patients (mean difference, 43.7
      minutes; 95% confidence interval, 18.6-68.7 minutes; P < 0.001). There was a
      positive correlation between MTT and excess arm volume (r = 0.64; P = 0.04) and
      number of lymph nodes removed (r = 0.65; P = 0.03) but no correlation between
      visual score and MTT. CONCLUSION: Measurements of MTT were able to discriminate
      lymphedema from healthy arm and MTT correlated with relevant markers for
      lymphedema severity. We encourage further research using the MTT approach for
      monitoring lymphedema and evaluation of treatment response.

PMID- 28740777
TI  - Prepectoral Breast Reconstruction or Muscle-Sparing Technique with the Braxon
      Porcine Acellular Dermal Matrix.
AB  - Supplemental Digital Content is available in the text.

PMID- 28740778
TI  - Takotsubo Cardiomyopathy after Head and Neck Reconstructive Surgery.
AB  - Takotsubo cardiomyopathy (TCM) is a form of transient heart failure that
      clinically mimics acute coronary syndrome and is characterized by left
      ventricular wall motion abnormalities. The pathophysiology of TCM is not well
      established. TCM is often preceded by emotional or physical stress and may occur
      after surgery. We present 3 cases of TCM occurring after head and neck
      reconstructive surgery. Echocardiography plays a central role in the diagnosis of
      TCM. Left ventricular wall motion abnormalities extend beyond the territory of a
      single coronary artery. Coronary angiography and cardiac computed tomography can
      demonstrate the absence of coronary atherosclerosis and are useful for confirming
      the diagnosis of TCM. Particularly after reconstructive surgery, it is necessary
      to carefully monitor fluid replacement to avoid dehydration, which may compromise
      flap blood flow, although congestive heart failure is the most common
      complication of TCM. It is important to encourage ambulation as soon as possible,
      while considering the degree of cardiac impairment.

PMID- 28740779
TI  - Using the Venous Pectoral Branch from the Thoracoacromial System as a Lifeboat in
      Autologous Breast Reconstruction.
AB  - The most common recipient vessels for autologous free flap breast reconstruction
      are the internal mammary vessels. At times, there are problems with the exposed
      internal mammary vein (IMV) that require other options such as using the
      contralateral IMV, superior rib resection to access proximal IMV, retrograde IMV
      use, and thoracodorsal vein access with or without a vein graft. This case
      demonstrates using the pectoral branch of the thoracoacromial venous system
      without a vein graft as a lifeboat option when the IMV is not suitable for
      anastomosis. C.W. was a 65-year-old female who underwent right-sided mastectomy
      with placement of a tissue expander. After adjuvant radiation therapy, C.W.
      underwent deep inferior epigastric perforator free flap breast reconstruction.
      During exposure of the internal mammary artery and IMV, an iatrogenic venotomy
      occurred that precluded the use of this vessel as a reliable recipient. The deep
      inferior epigastric perforator flap pedicle was then dissected proximal to
      isolate the artery and vein, and the vein was successfully anastomosed to the
      venous pectoral branch of the thoracoacromial system. The postoperative course
      was uneventful and patient was discharged home on postoperative day 4. Using the
      venous pectoral branch of the thoracoacromial is a safe and valuable option that
      can be considered in difficult situations when the IMV is not a suitable option.

PMID- 28740780
TI  - Using the Gluteal Artery Perforator Flap to Reconstruct Sacral Sore.
AB  - Supplemental Digital Content is available in the text.

PMID- 28740781
TI  - Direct to Implant Reconstruction in Nipple Sparing Mastectomy: Patient Selection
      by Preoperative Digital Mammogram.
AB  - BACKGROUND: Digital mammography clearly distinguishes gland tissue density from
      the overlying nonglandular breast tissue coverage, which corresponds to the
      existing tissue between the skin and the superficial layer of the fascia
      superficialis surrounding the gland (i.e., dermis and subcutaneous fat).
      Preoperative digital imaging can determine the thickness of this breast tissue
      coverage, thus facilitating planning and reducing the rate of necrotic
      complications after direct to implant (DTI) reconstruction in nipple sparing
      mastectomy (NSM). METHODS: Thirty NSMs in 22 patients with type 3 tissue coverage
      (subcutaneous tissue thickness of 2 cm or more) were selected for DTI
      reconstruction after NSM to evaluate immediate skin flap/nipple areola complex
      ischemic complications and patient satisfaction. RESULTS: We experienced no wound
      healing problems or ischemic complications immediately after surgery in our
      population. Only 1 seroma was observed as a short-term complication. Quality of
      life and patients' satisfaction level were optimal at 3 and 6 months follow-up,
      respectively. The aesthetic results have been evaluated as good/excellent in all
      cases. CONCLUSIONS: DTI immediate reconstruction with silicone implants following
      NSM appears to be a safe option in selected cases with enough tissue coverage,
      also providing a high level of patient satisfaction. The possibility of selecting
      cases for this procedure according to the preoperative digital mammogram showing
      more than 2 cm of superficial tissues thickness may help reducing the risk of
      immediate ischemic complications.

PMID- 28740782
TI  - A Population-Based Exploration of the Social Implications Associated with Cleft
      Lip and/or Palate.
AB  - BACKGROUND: Clefts of the lip and/or palate (CL/P) carry a social stigma that
      often causes psychosocial stress. The purpose of this study was to consider the
      association of cleft phenotype and age with self-reported aspects of psychosocial
      stress. METHODS: Children with nonsyndromic CL/P and unaffected children born
      between 1997 and 2003 were identified through the North Carolina Birth Defects
      Monitoring Program and North Carolina birth records, respectively. The
      psychosocial concerns of children with CL/P were assessed via a 29-question
      subset of a larger survey. Responses were analyzed according to school age and
      cleft phenotype (cleft lip with/without cleft alveolus, CL +/- A; cleft palate
      only, CP; or cleft lip with cleft palate, CL + P). RESULTS: Surveys were returned
      for 176 children with CL/P and 333 unaffected children. When compared with
      unaffected children, responses differed for CL +/- A in 4/29 questions, for CP in
      7/29 questions, and for CL + P in 8/29 questions (P < 0.05). When stratified by
      school age, children with CL/P in elementary, middle, and high school differed
      from unaffected children by 1/29, 7/29, and 2/29 questions, respectively. Middle
      school-aged children with CL/P were more affected by aesthetic concerns,
      bullying, and difficulties with friendship, and social interaction. Children with
      CL + P reported more severe aesthetic-related concerns than children with CL +/-
      A or CP but experienced similar speech-related distress as children with CP only.
      CONCLUSION: Social implications associated with CL/P are most pronounced during
      middle school, and less so during elementary and high school. This information
      identifies areas of social improvement aimed at reducing the stigma of CL/P.

PMID- 28740783
TI  - Bone Morphogenetic Protein-7 Enhances Degradation of Osteoinductive Bioceramic
      Implants in an Ectopic Model.
AB  - BACKGROUND: The aim of the present study was to evaluate the degradation pattern
      of highly porous bioceramics as well as the bone formation in presence of bone
      morphogenetic protein 7 (BMP-7) in an ectopic site. METHODS: Novel calcium
      phosphate ceramic cylinders sintered at 1,300 degrees C with a total porosity of
      92-94 vol%, 45 pores per inch, and sized 15 mm (O) * 5 mm were grafted on the
      musculus latissimus dorsi bilaterally in 10 Gottingen minipigs: group I (n = 5):
      hydroxyapatite (HA) versus biphasic calcium phosphate (BCP), a mixture of HA and
      tricalcium phosphate (TCP) in a ratio of 60/40 wt%; group II (n = 5): TCP versus
      BCP. A test side was supplied in situ with 250 MUg BMP-7. Fluorochrome bone
      labeling and computed tomography were performed in vivo. Specimens were evaluated
      14 weeks after surgery by environmental scanning electron microscopy,
      fluorescence microscopy, tartrate-resistant acid phosphatase, and pentachrome
      staining. RESULTS: Bone formation was enhanced in the presence of BMP-7 in all
      ceramics (P = 0.001). Small spots of newly formed bone were observed in all
      implants in the absence of BMP-7. Degradation of HA and BCP was enhanced in the
      presence of BMP-7 (P = 0.001). In those ceramics, osteoclasts were observed. TCP
      ceramics were almost completely degraded independently of the effect of BMP-7
      after 14 weeks (P = 0.76), osteoclasts were not observed. CONCLUSIONS: BMP-7
      enhanced bone formation and degradation of HA and BCP ceramics via osteoclast
      resorption. TCP degraded via dissolution. All ceramics were osteoinductive. Novel
      degradable HA and BCP ceramics in the presence of BMP-7 are promising bone
      substitutes in the growing individual.

PMID- 28740784
TI  - Recovery from Bell Palsy after Transplantation of Peripheral Blood Mononuclear
      Cells and Platelet-Rich Plasma.
AB  - Peripheral blood mononuclear cells (PBMCs) are multipotent, and plasma contains
      growth factors involving tissue regeneration. We hypothesized that
      transplantation of PBMC-plasma will promote the recovery of paralyzed facial
      muscles in Bell palsy. This case report describes the effects of PBMC-plasma
      transplantations in a 27-year-old female patient with right side Bell palsy. On
      the affected side of the face, the treatment resulted in both morphological and
      functional recovery including voluntary facial movements. These findings suggest
      that PBMC-plasma has the capacity of facial muscle regeneration and provides a
      promising treatment strategy for patients suffering from Bell palsy or other
      neuromuscular disorders.

PMID- 28740785
TI  - Coronary Artery Disease in Patients with Critical Limb Ischemia Undergoing Major
      Amputation or Not.
AB  - BACKGROUND: Due to the increase of elderly and diabetes patients, surgeons
      encounter patients requiring treatment of critical limb ischemia (CLI) in the
      presence of systemic arteriosclerotic diseases. In this study, we retrospectively
      investigated the prevalence of coronary artery disease (CAD) in patients with CLI
      who underwent major (above-the-ankle) amputation or nonmajor amputation (below
      the-ankle amputation or debridement of wound). METHODS: We retrospectively
      investigated 129 consecutive patients surgically managed for CLI in our
      institution between January 2013 and December 2015. The prevalence of CAD was
      defined as a cardiac treatment history or significant vascular stenosis (stenosis
      of > 75%). The outcomes were compared between patients who underwent major
      amputation (n = 36) and nonmajor amputation (n = 93). Additionally, archived
      record of 566 patients treated nonsurgically by percutaneous transluminal
      angioplasty in our institution was investigated to evaluate patients with milder
      peripheral artery disease. RESULTS: CAD was present in 83 patients (69%),
      including 82% of patients who underwent major amputation and 63% of nonmajor
      amputation group. The prevalence of CAD was significantly higher in the major
      amputation group (P = 0.042). Ejection fraction was not significantly different
      (P > 0.05). Among the 566 CLI patients treated by only percutaneous transluminal
      angioplasty, 227 (40%) had CAD, which was a significantly lower prevalence than
      those surgically treated (P < 0.001). CONCLUSIONS: The presence of CAD is more
      frequent in CLI patients who require extended surgical management of the limb
      than in those who do not. Evaluation of CAD and careful perioperative management
      are important for patients with CLI patients.

PMID- 28740786
TI  - Virtual Surgical Planning for Mandibular Distraction in Infants with Robin
      Sequence.
AB  - Mandibular distraction osteogenesis (MDO) successfully relieves obstructive sleep
      apnea in many infants with Robin sequence. Preoperative virtual surgical planning
      and fabrication of three-dimensionally printed cutting guides may lead to further
      improvements in the MDO technique and decrease the risk for damage to adjacent
      structures such as developing teeth and the inferior alveolar nerve. This report
      presents an algorithm for virtual surgical planning and three-dimensionally
      printing of cutting guides for MDO in infants with RS.

PMID- 28740787
TI  - Costs and Economics of Skin Cancer Management, Mohs Surgery, and Surgical
      Reconstruction.

PMID- 28740788
TI  - Acellular Dermal Matrix Versus Inferior Deepithelialized Flap Breast
      Reconstruction: Equivalent Outcomes, with Increased Cost.
AB  - BACKGROUND: Approximately 250,000 new cases of breast cancer are diagnosed yearly
      in the U.S. resulting in more postmastectomy breast reconstructions (PMBRs). The
      acellular dermal matrix (ADM) expander-implant method became popular in the mid
      2000s, but newer techniques such as the inferior deepithelialized flap (IDF) has
      more recently been described. We hypothesize that ADMs and IDFs provide
      comparable aesthetic outcomes, with no difference in complication rates and
      operative characteristics. METHODS: A retrospective, single-institution study was
      performed between July 1, 2012, and June 30, 2014, examining all PMBR's (ADM and
      IDF). Outcomes were categorized as clinical (e.g., complications requiring
      surgical intervention) or aesthetic. RESULTS: A total of 65 patients (41 ADM; 24
      IDF; mean age, 53.4 +/- 10.7 years) were included, with 101 PMBR's evaluated (63
      ADM and 38 IDF). Patients who underwent IDFs had higher body mass index (32
      versus 25; P < 0.01) and higher grades of breast ptosis. Major complication rates
      were similar between ADM and IDF groups (22% versus 31.5%; P = 0.34). There were
      no differences in aesthetic outcomes between groups (rater intraclass
      correlation, 0.92). The average IDF breast reconstruction took nearly 30 minutes
      longer per reconstructed side (192 minutes versus 166 minutes; P = 0.02), but
      operative costs were more expensive for the ADM breast reconstruction.
      CONCLUSIONS: The IDF procedure took 30 minutes longer for each reconstructed
      side, without significant differences in complications or aesthetic outcomes
      between the 2 PMBRs. IDF reconstructions may be more suitable for patients with
      grade 3 breast ptosis and higher body mass index. Further studies should focus on
      long-term outcomes and value-based approaches to PMBR.

PMID- 28740789
TI  - A Unique Lymphaticovenous Supermicrosurgery Training Curriculum: Reflections on
      Validation and Competency Thresholds.
AB  - Supermicrosurgery is becoming a commonly used technique in various subspecialties
      of reconstructive surgery. However, there is a lack of standardization and
      validation in novel supermicrosurgical training. Current simulation training
      programs are not adequately focused on the challenges encountered during clinical
      supermicrosurgery practice. This article describes the authors' experience
      utilizing a supermicrosurgery competency-based training curriculum, in a
      simulation-based environment, toward safe clinical practice for lymphatic
      submillimeter supermicrovascular surgery. This article demonstrates the senior
      authors' (I.K.) Halstedian competency-based curriculum for lymphaticovenous
      anastomosis training. Further, a step-by-step training utilizing the chicken
      thigh and the living rat high fidelity simulation models, which subsequently
      allows supervised one-to-one clinical training with verified clinical competency
      outcomes, are demonstrated.

PMID- 28740790
TI  - An Extremely Rare Condition: Unilateral and Isolated Temporalis Muscle
      Hypertrophy.
AB  - Unilateral and isolated temporalis muscle hypertrophy is an extremely rare
      condition causing cosmetic problems and pain in the temporal region. Up to date,
      8 isolated and unilateral cases were reported in the English literature. In this
      article, the authors report 2 new cases of unilateral isolated temporal muscle
      hypertrophy.

PMID- 28740791
TI  - Reconstruction of Severely Crushed Fingertip Amputations with Basic Fibroblast
      Growth Factor Slow Release System.
AB  - Supplemental Digital Content is available in the text.

PMID- 28740792
TI  - Team Work: Mastectomy, Reconstruction, and Radiation.

PMID- 28740793
TI  - Donor-Site Complications and Remnant of Rectus Abdominis Muscle Status after
      Transverse Rectus Abdominis Myocutaneous Flap Reconstruction.
AB  - BACKGROUND: Transverse rectus abdominis myocutaneous (TRAM) flap reconstruction
      after mastectomy in breast cancer patients has become one of the milestones in
      breast reconstruction. There are several techniques that have been used in an
      attempt to minimize untoward complications. We present the whole muscle with
      partial sheath-sparing technique that focuses on the anatomy of arcuate line and
      the closure of the anterior abdominal wall techniques with mesh and determine
      factors associated with its complications and outcomes. METHODS: We
      retrospectively and prospectively review the results of 30 pedicled TRAM flaps
      that were performed between November 2013 and March 2016, focusing on outcomes
      and complications. RESULTS: Among the 30 pedicled TRAM flap procedures in 30
      patients, there were complications in 5 patients (17%). Most common complications
      were surgical-site infection (7%). After a median follow-up time of 15 months, no
      patient developed abdominal wall hernia or bulging in daily activities in our
      study, but 6 patients (20%) had asymptomatic abdominal wall bulging when
      exercised. Significant factors related to asymptomatic exercised abdominal wall
      bulging included having a body mass index of more than 23 kg/m2. CONCLUSION:
      Pedicled TRAM flap by using the technique of the whole muscle with partial sheath
      sparing technique combined with reinforcement above the arcuate line with mesh
      can reduce the occurrence of abdominal bulging and hernia.

PMID- 28740794
TI  - Tissue Expanders and Proton Beam Radiotherapy: What You Need to Know.
AB  - Proton beam radiotherapy (PBR) has gained acceptance for the treatment of breast
      cancer because of unique beam characteristics that allow superior dose
      distributions with optimal dose to the target and limited collateral damage to
      adjacent normal tissue, especially to the heart and lungs. To determine the
      compatibility of breast tissue expanders (TEs) with PBR, we evaluated the
      structural and dosimetric properties of 2 ex vivo models: 1 model with internal
      struts and another model without an internal structure. Although the struts
      appeared to have minimal impact, we found that the metal TE port alters PBR
      dynamics, which may increase proton beam range uncertainty. Therefore,
      submuscular TE placement may be preferable to subcutaneous TE placement to reduce
      the interaction of the TE and proton beam. This will reduce range uncertainty and
      allow for more ideal radiation dose distribution.

PMID- 28740795
TI  - Psychological Aspects of a Patient with Neglected Skin Tumor of the Scalp.

PMID- 28740796
TI  - Goldilocks Mastectomy: A Safe Bridge to Implant-Based Breast Reconstruction in
      the Morbidly Obese.
AB  - BACKGROUND: Reconstructive surgeons are encountering an increasing number of
      obese women requiring postmastectomy reconstruction. These patients are poor
      candidates for autologous and prosthetic-based reconstructions as they have a
      high rate of reconstructive failure, surgical complications, and poor aesthetic
      outcomes. We demonstrate here the utility of the previously described Goldilocks
      mastectomy with free nipple grafts as a safe bridge to second stage implant-based
      breast reconstruction. METHODS: Ten consecutive morbidly (BMI > 40) or super
      obese (BMI>50) women underwent bilateral Goldilocks mastectomy with free nipple
      grafts followed by second stage subpectoral implant placement at least three
      months postoperatively. Patients were assessed for implant-related complications
      including malposition, capsular contracture, dehiscence, and extrusion. RESULTS:
      Ten postmastectomy reconstructions in patients with BMIs ranging from 37 to 50
      with a mean BMI of 45 underwent bilateral Goldilocks mastectomy with free nipple
      grafts. Two patients had wound healing complications after Goldilocks mastectomy
      but were completely healed within 8 weeks. There were no instances of delayed
      wound healing or reconstructive failure after prosthetic placement. With at least
      9 months of follow-up on all patients, no patient has had a capsular contracture,
      significant malposition, or other complication requiring reoperation. CONCLUSION:
      The obese patient poses a significant reconstructive challenge for which no
      reproducible approach has been described. Here, we present a 2-stage strategy:
      the previously described Goldilocks mastectomy with free nipple grafts followed
      by second stage subpectoral definitive implant placement. This is the first
      proposed description of a reliable strategy for postmastectomy reconstruction in
      the morbidly and super obese.

PMID- 28740797
TI  - Pain Management in Abdominal Wall Reconstruction.
AB  - BACKGROUND: In abdominal wall reconstruction, adequate pain control and
      minimization of narcotic consumption are essential to improving patient outcomes
      and satisfaction. Previous studies have examined the role of individual
      strategies, such as neuraxial analgesia and multimodal analgesia. However, there
      has not been a study that examined all potential determinants of postoperative
      narcotic requirements, including intraoperative strategies. METHODS: Consecutive
      patients who underwent abdominal wall reconstruction were reviewed. Preoperative
      factors (chronic preoperative narcotic usage, indication for abdominal wall
      reconstruction, administration of neuraxial analgesia), intraoperative factors
      (intraoperative narcotics administered, method of mesh fixation), and
      postoperative factors (multimodal analgesia, complications) were collected. The
      main outcomes were daily amount of opioids used and length of hospital stay.
      RESULTS: Ninety-three patients were included in the study. Patients who had an
      epidural required lower doses of opioids postoperatively, while those on chronic
      preoperative opioids, those whose mesh was fixated using transfascial sutures,
      and those who received large doses of opioids intraoperatively required higher
      doses of postoperative opioids. Hospital length of stay was longer in patients
      who received transfascially sutured mesh and those on chronic opioids
      preoperatively. CONCLUSIONS: This study provides potential strategies to improve
      pain control and minimize narcotic consumption postoperatively in patients
      undergoing abdominal wall reconstruction. Intraoperative administration of
      opioids should be minimized to avoid the development of tolerance. Epidural
      analgesia reduces postoperative narcotic requirement and may be especially
      beneficial in patients at highest risk for postoperative pain, including those on
      chronic opioids, and those in whom transfascial sutures are used for mesh
      fixation.

PMID- 28740798
TI  - Gender Confirmation Surgery: Cosmetic or Reconstructive Procedure?

PMID- 28740801
TI  - Concepts of 'self' in delusion resolution.

PMID- 28740802
TI  - Selective impairment of global motion integration, but not global form detection,
      in schizophrenia and bipolar affective disorder.
AB  - Recent evidence suggests that schizophrenia is associated with impaired
      processing of global visual motion, but intact processing of global visual form.
      This project assessed whether preserved visual form detection in schizophrenia
      extended beyond low-level pattern discrimination to a naturalistic form-detection
      task. We assessed both naturalistic form detection and global motion detection in
      individuals with schizophrenia spectrum disorder, bipolar affective disorder, and
      healthy controls. Individuals with schizophrenia spectrum disorder and bipolar
      affective disorder were impaired relative to healthy controls on the global
      motion task, but not the naturalistic form-detection task. Results indicate that
      preservation of visual form detection in these disorders extends beyond
      configural forms to naturalistic object processing.

PMID- 28740803
TI  - Intact unconscious processing of eye contact in schizophrenia.
AB  - The perception of eye gaze is crucial for social interaction, providing essential
      information about another person's goals, intentions, and focus of attention.
      People with schizophrenia suffer a wide range of social cognitive deficits,
      including abnormalities in eye gaze perception. For instance, patients have shown
      an increased bias to misjudge averted gaze as being directed toward them. In this
      study we probed early unconscious mechanisms of gaze processing in schizophrenia
      using a technique known as continuous flash suppression. Previous research using
      this technique to render faces with direct and averted gaze initially invisible
      reveals that direct eye contact gains privileged access to conscious awareness in
      healthy adults. We found that patients, as with healthy control subjects, showed
      the same effect: faces with direct eye gaze became visible significantly faster
      than faces with averted gaze. This suggests that early unconscious processing of
      eye gaze is intact in schizophrenia and implies that any misjudgments of gaze
      direction must manifest at a later conscious stage of gaze processing where
      deficits and/or biases in attributing mental states to gaze and/or beliefs about
      being watched may play a role.

PMID- 28740804
TI  - Predicting employment status and subjective quality of life in patients with
      schizophrenia.
AB  - Although impaired social functioning, particularly poor employment status, is a
      cardinal feature of patients with schizophrenia and leads to decreased quality of
      life (QOL), few studies have addressed the relationship between these two
      clinical issues. The aim of this study was to determine whether employment status
      predicts subjective QOL and to evaluate a model in which functional capacity
      mediates the relationship between general cognitive performance and employment
      status. Ninety-three patients with schizophrenia were administered a
      comprehensive battery of cognitive tests, the UCSD Performance-based Skills
      Assessment-Brief version (UPSA-B), the Social Functioning Scale (SFS), and the
      Subjective Quality of Life Scale (SQLS). First, we evaluated a model for
      predicting the employment/occupation subscale score of the SFS using path
      analysis, and the model fitted well (chi2 (4) = 3.6, p = 0.46; CFI = 1.0; RMSEA <
      0.001, with 90% CIs: 0-0.152). Employment status was predicted by negative
      symptoms and functional capacity, which was in turn predicted by general
      cognitive performance. Second, we added subjective QOL to this model. In a final
      path model, QOL was predicted by negative symptoms and employment status. This
      model also satisfied good fit criteria (chi2 (7) = 10.3, p = 0.17; CFI = 0.987;
      RMSEA = 0.072, with 90% CIs: 0-0.159). The UPSA-B and SFS scores were moderately
      correlated with most measures of cognitive performance. These results support the
      notion that better employment status enhances subjective QOL in patients with
      schizophrenia.

PMID- 28740805
TI  - Altered emotional modulation of associative memory in first episode
      schizophrenia: An fMRI study.
AB  - Alterations of associative memory, resulting from perturbations within the medial
      temporal lobe, are well established in schizophrenia. So far, all the studies
      having examined associative memory in schizophrenia have limited ecological
      validity, as people experience various emotional stimuli in their life. As such,
      emotion must be taken into account in order to fully understand memory. Thus, we
      designed an fMRI study aimed at investigating neural correlates of the effects of
      emotions on associative memory in schizophrenia. Twenty-four first episode
      schizophrenia (FES) patients and 20 matched controls were instructed to memorize
      90 pairs of standardized pictures during a scanned encoding phase. Each of the 90
      pairs was composed of a scene and an unrelated object. Furthermore, trials were
      either neutral or emotional as a function of the emotional valence of the scene
      comprising each pair. FES patients exhibited lower performance for both
      conditions than controls, with greater deficits in regard to emotional versus
      neutral associations. fMRI analyses revealed that these deficits were related to
      lower activations in mnemonic and limbic regions. This study provides evidence of
      altered associative memory and emotional modulation in schizophrenia, resulting
      from dysfunctions in the cerebral networks underlying memory, emotion, and
      encoding strategies. Together, our results suggest that all these dysfunctions
      may be targets for new therapeutic interventions known to improve cognitive
      deficits in schizophrenia.

PMID- 28740806
TI  - Neuropsychological correlates of remission in chronic schizophrenia subjects: The
      role of general and task-specific executive processes.
AB  - BACKGROUND: Although cognitive deficits have consistently been characterized as
      core features of schizophrenia, they have not been incorporated into definitions
      of remission. Furthermore, just a few studies have examined the relationship
      between cognitive deficits and symptomatic remission. The main aim of the present
      study is to evaluate the executive functioning of nonremitted schizophrenia
      patients. METHODS: 72 remitted and 42 nonremitted schizophrenia patients, and 119
      healthy controls were examined. Subjects were tested with a comprehensive battery
      of cognitive tests, including a measure to assess the general components of
      executive functioning and individual tasks to tap the three specific executive
      dimensions assessed in the present study, namely updating, shifting and
      inhibition. RESULTS: Schizophrenia subjects performed poorly on general executive
      functioning and shifting tasks in comparison to healthy controls. Remitted
      subjects performed better than nonremitted on inhibition and updating tasks.
      Whereas being a male and showing decreases in updating increase the chances of
      being in the nonremitted schizophrenia subjects group, increases in shifting and
      updating enhance the odds of being in the healthy control group. CONCLUSION: The
      present findings suggest that executive function deficits are present in chronic
      schizophrenic patients. In addition, specific executive processes might be
      associated to symptom remission. Future studies examining prospectively first
      episode, drug naive patients diagnosed with schizophrenia may be especially
      elucidative.

PMID- 28740807
TI  - Attribution bias and social anxiety in schizophrenia.
AB  - Studies on attribution biases in schizophrenia have produced mixed results,
      whereas such biases have been more consistently reported in people with anxiety
      disorders. Anxiety comorbidities are frequent in schizophrenia, in particular
      social anxiety disorder, which could influence their patterns of attribution
      biases. The objective of the present study was thus to determine if individuals
      with schizophrenia and a comorbid social anxiety disorder (SZ+) show distinct
      attribution biases as compared with individuals with schizophrenia without social
      anxiety (SZ-) and healthy controls. Attribution biases were assessed with the
      Internal, Personal, and Situational Attributions Questionnaire in 41 individual
      with schizophrenia and 41 healthy controls. Results revealed the lack of the
      normal externalizing bias in SZ+, whereas SZ- did not significantly differ from
      healthy controls on this dimension. The personalizing bias was not influenced by
      social anxiety but was in contrast linked with delusions, with a greater
      personalizing bias in individuals with current delusions. Future studies on
      attribution biases in schizophrenia should carefully document symptom
      presentation, including social anxiety.

PMID- 28740808
TI  - e-Motional Training(r): Pilot study on a novel online training program on social
      cognition for patients with schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia have deficits in social cognition (SC), a
      construct that includes emotion perception (EP), social perception (SP), theory
      of mind (ToM) and attributive style (AS). The aim of our study was to assess the
      applicability, identify potential problems and obtain preliminary data on the
      efficacy of a new online training program on SC called e-Motional Training
      (ET(r)), which can be remotely administered and remotely supervised by a
      clinician. MATERIALS AND METHODS: A pre/post intervention pilot study was
      conducted with 21 patients with schizophrenia in the healthcare area of Ourense,
      Spain (12 patients were assigned to the intervention group and 9 in the control
      group). The control group received standard treatment (TAU) (occupational therapy
      and leisure group). The intervention group received TAU plus 12 sessions (1 hour
      per week) with ET(r) (including training modules on emotional perception and a
      short animated cartoon for ToM and AS training, including automated metacognitive
      feedback). Endpoints: EP (Ekman 60 Faces Test), ToM (Hinting Task, Faux Pas,
      Happe), AS (Ambiguous Intentions Hostility Questionnaire). RESULTS: ET(r) was
      shown to be an understandable, viable and pleasant program for the participants.
      After the intervention, statistically significant data (p < 0.05) were obtained
      for the EP, ToM and AS variables. CONCLUSION: ET(r) enables self-training in SC
      and online follow-up by the therapist, thereby covering the lack of online
      intervention instruments validated for patients with SC deficits. Our preliminary
      results demonstrate the feasibility of ET(r) and its possible efficacy in
      improving emotion recognition, ToM and AS.

PMID- 28740809
TI  - Dissociation mediates the relationship between peer victimization and
      hallucinatory experiences among early adolescents.
AB  - Peer victimization increases the risk of experiencing psychotic symptoms among
      clinical and general populations, but the mechanism underlying this association
      remains unclear. Dissociation, which is related to peer victimization and
      hallucinatory experiences, has been demonstrated as a significant mediator in the
      relation between childhood victimization and hallucinatory experience among adult
      patients with psychosis. However, no studies have examined the mediating effect
      of dissociation in a general early adolescent population. We examined whether
      dissociation mediates the relationship between peer victimization and
      hallucinatory experiences among 10-year-old adolescents using a population-based
      cross-sectional survey of early adolescents and their main parent (Tokyo Early
      Adolescence Survey; N = 4478). We examined the mediating effect of dissociation,
      as well as external locus of control and depressive symptoms, on the relationship
      between peer victimization and hallucinatory experiences using path analysis. The
      model assuming mediation effects indicated good model fit (comparative fit index
      = .999; root mean square error of approximation = .015). The mediation effect
      between peer victimization and hallucination via dissociation (standardized
      indirect effect = .038, p < .001) was statistically significant, whereas the
      mediation effects of depressive symptoms (standardized indirect effect = -.0066,
      p = 0.318) and external locus of control (standardized indirect effect = .0024, p
      = 0.321) were not significant. These results suggest that dissociation is a
      mediator in the relation between peer victimization and hallucinatory experiences
      in early adolescence. For appropriate intervention strategies, assessing
      dissociation and peer victimization as they affect hallucinatory experiences is
      necessary.

PMID- 28740810
TI  - Schizotypy and mindfulness: Magical thinking without suspiciousness characterizes
      mindfulness meditators.
AB  - Despite growing evidence for demonstrated efficacy of mindfulness in various
      disorders, there is a continuous concern about the relationship between
      mindfulness practice and psychosis. As schizotypy is part of the psychosis
      spectrum, we examined the relationship between long-term mindfulness practice and
      schizotypy in two independent studies. Study 1 included 24 experienced
      mindfulness practitioners (19 males) from the Buddhist tradition (meditators) and
      24 meditation-naive individuals (all males). Study 2 consisted of 28 meditators
      and 28 meditation-naive individuals (all males). All participants completed the
      Schizotypal Personality Questionnaire (Raine, 1991), a self-report scale
      containing 9 subscales (ideas of reference, excessive social anxiety, magical
      thinking, unusual perceptual experiences, odd/eccentric behavior, no close
      friends, odd speech, constricted affect, suspiciousness). Participants of study 2
      also completed the Five-Facet Mindfulness Questionnaire which assesses observing
      (Observe), describing (Describe), acting with awareness (Awareness), non-judging
      of (Non-judgment) and non-reactivity to inner experience (Non-reactivity) facets
      of trait mindfulness. In both studies, meditators scored significantly lower on
      suspiciousness and higher on magical thinking compared to meditation-naive
      individuals and showed a trend towards lower scores on excessive social anxiety.
      Excessive social anxiety correlated negatively with Awareness and Non-judgment;
      and suspiciousness with Awareness, Non-judgment and Non-reactivity facets across
      both groups. The two groups did not differ in their total schizotypy score. We
      conclude that mindfulness practice is not associated with an overall increase in
      schizotypal traits. Instead, the pattern suggests that mindfulness meditation,
      particularly with an emphasis on the Awareness, Non-judgment and Non-reactivity
      aspects, may help to reduce suspiciousness and excessive social anxiety.

PMID- 28740811
TI  - Change in daytime sleepiness and cognitive function in a 6-month, double-blind
      study of lurasidone and quetiapine XR in patients with schizophrenia.
AB  - Daytime sleepiness is a commonly reported adverse effect associated with
      psychotropic agents that may impair cognitive performance and functioning. The
      objective of this post-hoc analysis was to evaluate the long-term effects of
      lurasidone and quetiapine XR on daytime sleepiness and neurocognitive performance
      during a 6-month, double-blind continuation study, in subjects who completed an
      initial 6-week, randomized, placebo-controlled trial comparing these agents.
      Daytime sleepiness, cognitive performance, and health-related quality of life
      were assessed with the Epworth Sleepiness Scale (ESS), CogState computerized
      battery, and the Quality of Well-Being (QWB-SA) Scale, respectively. Treatment
      with flexible-dose lurasidone 40-160 mg/d, administered once daily in the
      evening, was associated with significantly reduced daytime sleepiness compared
      with flexibly dosed quetiapine XR 200-800 mg/d (p = 0.03, effect size = 0.36) at
      week 32 (month 6 of the continuation study endpoint). Incidence of markedly high
      sleepiness (ESS > 10) was significantly higher in the quetiapine XR (200-800
      mg/d) group compared with the lurasidone (40-160 mg/day) group at both months 3
      and 6 visits (p < 0.05). Lurasidone (40-160 mg/d) significantly improved
      neurocognitive performance compared to quetiapine XR (200-800 mg/d) before
      (effect size = 0.49) and after adjustment (effect size = 0.45) for sleepiness
      effect (p = 0.008 and 0.010, respectively). Increased daytime sleepiness was
      significantly associated with reduced neurocognitive performance (p = 0.019) and
      quality of well-being (p = 0.05). Our findings suggest that clinicians should
      actively monitor patients for the presence of daytime sleepiness due in part to
      its potential impact on neurocognitive performance and well-being.

PMID- 28740812
TI  - Decoding emotion of the other differs among schizophrenia patients and
      schizoaffective patients: A pilot study.
AB  - The deficit in ability to attribute mental states such as thoughts, beliefs, and
      intentions of another person is a key component in the functional impairment of
      social cognition in schizophrenia. In the current study, we compared the ability
      of persons with first episode schizophrenia (FE-SZ) and individuals with
      schizophrenia displaying symptomatic remission (SZ-CR) to decode the mental state
      of others with healthy individuals and schizoaffective patients. In addition, we
      analyzed the effect of dopamine-related genes polymorphism on the ability to
      decode the mental state of another, and searched for different genetic
      signatures. Our results show that overall, individuals with schizophrenia
      performed worse in the "Reading the Mind in the Eyes" (eyes) test, a simple well
      defined task to infer the mental state of others than healthy individuals. Within
      the schizophrenia group, schizoaffective scored significantly higher than FE-SZ,
      SZ-CR, and healthy individuals. No difference was observed in performance between
      FE-SZ and SZ-CR subjects. Interestingly, FE-SZ and SZ-CR, but not schizoaffective
      individuals, performed worse in decoding negative and neutral emotional valance
      than the healthy control group. At the genetic level, we observed a significant
      effect of the DAT genotype, but not D4R genotype, on the eyes test performance.
      Our data suggest that understanding the mental state of another person is a trait
      marker of the illness, and might serve as an intermediate phenotype in the
      diagnostic process of schizophrenia disorders, and raise the possibility that DA
      related DAT gene might have a role in decoding the mental state of another
      person.

PMID- 28740813
TI  - Social cognition in patients at ultra-high risk for psychosis: What is the
      relation to social skills and functioning?
AB  - OBJECTIVE: Patients at ultra-high risk (UHR) for psychosis show significant
      impairments in functioning. It is essential to determine which factors influence
      functioning, as it may have implications for intervention strategies. This study
      examined whether social cognitive abilities and clinical symptoms are associated
      with functioning and social skills. METHODS: The study included 65 UHR patients
      and 30 healthy controls. Social cognitive function, social skills, and a broad
      range of functioning measures were assessed. RESULTS: The UHR patients
      demonstrated significant decrements on The Awareness of Social Inferences Task
      total score (p = .046, d = .51), and on the CANTAB emotion recognition task total
      percent correct (p = .023, d = .54) displaying particular difficulties in
      negative affect recognition. The patients exhibited significant impairments in
      social skills measured with the High Risk Social Challenge (p?.001, d = 1.05).
      Aspects of emotion recognition were associated with role functioning and social
      skill performance. The level of attributional bias was associated with overall
      functioning, and theory of mind ability was associated with self-reported
      functioning. Negative symptoms were associated with all measures of functioning
      (p <= .05). CONCLUSION: Significant impairments in social cognition and social
      skills were found in UHR patients. The patients' social cognitive function was
      associated with overall functioning and social skills. Negative symptoms appear
      to play an important role for functioning. Research is needed to investigate how
      the relations between social cognition, social skills and functioning develop
      from the UHR state to the stage of manifest illness. Research into how deficits
      in social cognition and social skills can be ameliorated in UHR patients is
      warranted.

PMID- 28740814
TI  - Validation of the cognitively normal range and below normal range subtypes in
      chronically hospitalized patients with schizophrenia.
AB  - BACKGROUND: Many studies have found a substantial minority of patients whose
      performance puts them within the normal range of neuropsychological functioning.
      Recently, a study has seen the delineation of two neurocognitive subtypes of
      schizophrenia -'cognitively normal range' (CNR) and 'below normal range' (BNR) -
      based on neurocognitive performance across multiple domains. METHODS: The
      participants were from two studies that collected neurocognitive, psychopathology
      and social function data between 2008 and 2015. In total the complete data from
      one hundred and thirty one patients of Han Chinese ethnicity with schizophrenia
      were collected on 21 neurocognitive indexes (assessing the domains of processing
      speed, attention, working memory, verbal memory, visual memory, reasoning and
      problem solving and IQ). Fifty-five patients of the one hundred and thirty one
      participants received additional ratings on their psychopathology and social
      functions. An exploratory graphic analysis was conducted on the neurocognitive
      measures for the entire sample. Difference analyses were also performed according
      to the aims of the study using the Independent t test, Chi-square test, and
      Cohen's d effect size. RESULTS: Analyses revealed the existence of two patients
      subtypes. The post hoc tests showed that there were significant differences on
      all of their neurocognitive measures and on most of the psychopathology and
      social functions between the two subtypes. These two subtypes could be referred
      to as the CNR subtype and the BNR subtype respectively. CONCLUSIONS: There are
      neurocognitive subtypes of schizophrenia with differential illness
      characteristics comparable with the CNR and the BNR in patients of Han Chinese
      ethnicity with schizophrenia.

PMID- 28740815
TI  - Positive schizotypy and negative schizotypy are associated with differential
      patterns of episodic memory impairment.
AB  - Cognitive impairment is a hallmark of schizophrenia; however, studies have not
      comprehensively examined such impairments in non-clinically ascertained
      schizotypic young adults. The present study employed a series of measures to
      assess episodic memory in high positive schizotypy, high negative schizotypy, and
      comparison groups (each group n = 25). Consistent with diminished cognitive
      functioning seen in negative symptom schizophrenia, the negative schizotypy group
      exhibited deficits on free recall, recognition, and source memory tasks. The
      positive schizotypy group did not demonstrate deficits on the above mentioned
      tasks. However, in contrast to the other groups, the positive schizotypy group
      showed an unexpected set-size effect on the cued-recall task. Set-size effect,
      which refers to the finding that words that have smaller networks of associates
      tend to have a memory advantage, is usually found in associative-cuing, but not
      cued-recall, tasks. The finding for the positive schizotypy group is consistent
      with heightened spreading activation and reduced executive control suggested to
      underlie psychotic symptoms. The findings support a multidimensional model of
      schizotypy and schizophrenia, and suggest that positive and negative schizotypy
      involve differential patterns of cognitive impairment.

PMID- 28740816
TI  - Probability and magnitude evaluation in schizophrenia.
AB  - Alterations in reinforcement learning and decision making in schizophrenia have
      been linked with orbitofrontal cortex (OFC) dysfunction, a region critical for
      weighing reward magnitude in the calculation of expected value (EV). However,
      much of this work has used complex tasks that require combined learning and EV
      calculation. Here we used a simple "Roulette" task that examined the calculation
      of EV directly through a combination of text and/or pictorial representation of
      reward probability and magnitude. Forty-four people with schizophrenia and 30
      controls were recruited. Patients were less sensitive to adjustments in a
      parameter combining probability and magnitude into one EV construct. Breaking
      down the construct into independent contributions of probability and magnitude,
      we found that negative symptoms were associated with magnitude sensitivity. This
      is consistent with the hypothesized role of OFC in actively representing
      magnitude and the notion that negative symptoms may involve a failure to
      appropriately estimate and use future reward magnitude to guide decision making.

PMID- 28740817
TI  - Impaired retrieval processes evident during visual working memory in
      schizophrenia.
AB  - Prominent working memory (WM) deficits have been observed in people with
      schizophrenia (PSZ) across multiple sensory modalities, including the
      visuospatial realm. Electrophysiological abnormalities noted during early visual
      processing as well as later cognitive functions in PSZ may underlie deficiencies
      in WM ability, though the mechanisms linking behavior to neural responses are not
      well understood. WM dysfunction has also been observed in biological relatives of
      PSZ (REL) and therefore may be a manifestation of genetic liability for the
      disorder. We administered a delayed response visuospatial WM task to 23 PSZ, 30
      of their REL, and 37 healthy controls (CTRL) to better understand the
      contributions of neural abnormalities to WM performance deficits associated with
      schizophrenia. PSZ performed more poorly on the WM task and failed to effectively
      process distractor stimuli as well as CTRL and REL. N1 electrophysiological
      responses to probes during retrieval differentiated the type and locations of
      stimuli presented during encoding in CTRL. Retrieval N1 responses in PSZ,
      however, failed to do so, while retrieval responses in REL showed more pronounced
      differentiation of stimulus features during encoding. Furthermore, neural
      responses during retrieval predicted behavioral performance in PSZ and REL, but
      not CTRL. These results suggest that retrieval processes are particularly
      important to efficient visuospatial WM function in PSZ and REL, and support
      further investigation of WM retrieval as a potential target for improving overall
      WM function through clinical intervention.

PMID- 28740818
TI  - Disrupted latent inhibition in individuals at ultra high-risk for developing
      psychosis.
AB  - The addition of off-the-shelf cognitive measures to established prodromal
      criteria has resulted in limited improvement in the prediction of conversion to
      psychosis. Tests that assess cognitive processes central to schizophrenia might
      better identify those at highest risk. The latent inhibition paradigm assesses a
      subject's tendency to ignore irrelevant stimuli, a process integral to healthy
      perceptual and cognitive function that has been hypothesized to be a key deficit
      underlying the development of schizophrenia. In this study, 142 young people at
      ultra high-risk for developing psychosis and 105 controls were tested on a within
      subject latent inhibition paradigm. Additionally, we later inquired about the
      strategy that each subject employed to complete the test, and further
      investigated the relationship between reported strategy and the extent of latent
      inhibition exhibited. Unlike controls, ultra high-risk subjects did not
      demonstrate a significant latent inhibition effect. This difference between
      groups became greater when controlling for strategy. The lack of latent
      inhibition effect in our ultra high-risk sample suggests that individuals at
      ultra high-risk for psychosis are impaired in their allocation of attentional
      resources based on past predictive value of repeated stimuli. This fundamental
      deficit in the allocation of attention may contribute to the broader array of
      cognitive impairments and clinical symptoms displayed by individuals at ultra
      high-risk for psychosis.

PMID- 28740819
TI  - Cognitive insight and functional outcome in schizophrenia; a multi-center
      collaborative study with the specific level of functioning scale-Japanese
      version.
AB  - The Specific Levels of Functioning Scale (SLOF) has been reported to provide a
      measure of social function in patients with schizophrenia. The aim of this multi
      center study was to determine convergent validity of the Japanese version of
      SLOF, and if cognitive insight would be associated with social function. Fifty
      eight patients with schizophrenia participated in the study. Social function,
      neurocognition, and daily activity skills were evaluated by the Social
      Functioning Scale (SFS), Brief Assessment of Cognition in Schizophrenia (BACS)
      and UCSD Performance-based Skills Assessment-Brief (UPSA-B), respectively. We
      also assessed cognitive insight with the Beck Cognitive Insight Scale (BCIS).
      Significant relationships were noted between scores on the SLOF vs. those of the
      SFS, BACS, UPSA-B, and BCIS. Specifically, the correlation between performance on
      the UPSA-B and SLOF scores was significantly more robust compared to the
      correlation between performance on the UPSA-B and scores on the SFS. Similarly,
      the correlation between scores on the BACS and SLOF tended to be more robust than
      that between the BACS and SFS. Importantly, while the correlation between scores
      on the BCIS and SLOF reached significance, it was not so between scores on the
      BCIS and SFS. The SLOF Japanese version was found to provide a measure of social
      consequences in patients with schizophrenia. Importantly, this study is the first
      to indicate the relationship between cognitive insight and social function
      evaluated by the SLOF. This finding is consistent with the observation that SLOF
      scores were considerably associated with performances on objective functional
      measures.

PMID- 28740820
TI  - Compared to high and low cannabis use, moderate use is associated with fewer
      cognitive deficits in psychosis.
AB  - Literature on the relationship of cannabis use and cognition in schizophrenia
      provides the paradoxical view that cannabis use is sometimes linked with less
      severe impairment in neurocognition. This paper explored the possibility that
      this is a reflection of a dose related response between lifetime cannabis use and
      two forms of cognition, neurocognition and metacognition, in schizophrenia. It
      was hypothesized that three groups of patients could be differentiated, those
      with (1) little to no cannabis use with poor levels of cognition, (2) moderate
      cannabis use and relatively better levels of cognition and (3) high cannabis use
      with relatively poorer levels of cognition. Sixty-six adults with schizophrenia
      completed assessments of neurocognition, metacognition and months of lifetime
      cannabis use. A k-means cluster analysis yielded three distinct groups based on
      these assessments. The clusters included: (1) low cannabis/poor cognition (n =
      34); (2) heavy cannabis/moderately impaired cognition (n = 10); and (3) moderate
      cannabis/higher cognition (n = 22). Consistent with our hypothesis, participants
      with high and moderate lifetime cannabis use had lesser impairment of
      neurocognition and metacognition compared to low lifetime cannabis use.
      Participants with moderate lifetime cannabis use also had lesser impairment of
      metacognition compared to low and heavy use. These findings suggest that a dose
      related relationship exists between cannabis use and cognition. Results could be
      due to an influence of pre-existing cognitive level on likelihood of lifetime
      cannabis use, or to an interaction between use and cognitive function.

PMID- 28740821
TI  - Validating the construct of aberrant salience in schizophrenia - Behavioral
      evidence for an automatic process.
AB  - Suspecting significance behind ordinary events is a common feature in psychosis
      and it is assumed to occur due to aberrant salience attribution. The Salience
      Attribution Test (SAT; Roiser et al., 2009) measures aberrant salience as a bias
      towards one out of two equally reinforced cue features as opposed to adaptive
      salience towards features indicating high reinforcement. This is the first study
      to validate the latent constructs involved in salience attribution in patients.
      Forty-nine schizophrenia patients and forty-four healthy individuals completed
      the SAT, a novel implicit salience paradigm (ISP), a reversal learning task and a
      neuropsychological test battery. First, groups were compared on raw measures.
      Second and within patients, these were correlated and then used for a principal
      component analysis (PCA). Third, sum scores matching the correlation and
      component pattern were correlated with psychopathology. Compared to healthy
      individuals, patients exhibited more implicit aberrant salience in the SAT and
      ISP and less implicit and explicit adaptive salience attribution in the SAT.
      Implicit aberrant salience from the SAT and ISP positively correlated with each
      other and negatively with reversal learning. Whereas explicit aberrant salience
      was associated with cognition, implicit and explicit adaptive salience were
      positively correlated. A similar pattern emerged in the PCA and implicit aberrant
      salience was associated with negative symptoms. Taken together, implicit aberrant
      salience from the SAT and ISP seems to reflect an automatic process that is
      independent from deficient salience ascription to relevant events. Its positive
      correlation with negative symptoms might reflect motivational deficits present in
      chronic schizophrenia patients.

PMID- 28740822
TI  - Neurological soft signs: Effects of trait schizotypy, psychological distress and
      auditory hallucination predisposition.
AB  - Schizotypy is regarded as a trait vulnerability for psychotic disorders, yet
      alone is insufficient for development of a diagnosable disorder. Additional
      symptoms and psychological distress are necessary for help seeking and transition
      from an at risk mental state to a clinical diagnosis. The present study
      investigated the interaction between trait schizotypy, state auditory verbal
      hallucination (AVH) predisposition, distress and handedness for the expression of
      neurological soft signs (NSS), a neurodevelopmental vulnerability factor for
      psychosis. Cluster analysis formed schizotypy groups statistically across the
      dimensions captured by the SPQ. It was hypothesized that schizotypy and AVH
      predisposition would interact, resulting in significantly greater NSS.
      Psychological distress and handedness were hypothesized to be significant
      covariates, accounting for some variance in the expression of NSS between the
      groups. A sample of University students (n = 327) completed the Schizotypal
      Personality Questionnaire, Launay-Slade Hallucination Scale, General Health
      Questionnaire and the Neurological Evaluation Scale (NES). Cluster Analysis
      revealed four schizotypy groups. Distress was not a significant covariate in any
      analysis. As expected, those with high overall schizotypy and high AVH
      predisposition expressed significantly greater Motor-Coordination NSS compared to
      those with high schizotypy and low AVH predisposition. Within the Mixed
      Interpersonal and Cognitive-Perceptual Schizotypy cluster, those with low AVH
      predisposition expressed significantly more Motor-Coordination NSS than those
      with high AVH predisposition. These findings suggest motor coordination NSS are
      detectable in schizotypy, and AVH predisposition appears to interact with these
      traits. This study highlights the importance of considering both trait and
      subclinical state risk factors when investigating risk for psychosis.

PMID- 28740823
TI  - Is performance on probed serial recall tasks in schizophrenia related to duration
      of Attentional Blink?
AB  - Schizophrenia is associated with a deficit in working memory, with the degree of
      working memory impairment related to the level of social and occupational
      functioning. This study tests the hypothesis that the working memory deficits in
      individuals with schizophrenia can be explained by slow processing of visual
      stimuli, as measured by the attentional blink (AB) task. Individuals with
      schizophrenia (SC) and controls (HC) were recruited from an early intervention
      service for psychosis and the local community. Data from 16 SC (11M/5F, mean =
      26.4 yo) and 20 age-matched HC (11M/9F, mean = 25.8 yo) were analyzed. Each
      subject performed an AB task to determine their AB duration, defined as the lag
      to reach their plateau performance (ltpp). As expected, mean AB duration in the
      SC group (575 ms) was significantly slower than HC (460 ms; p = 0.007). Recall
      accuracy of the SC group on a working memory task, a 6-item probed serial recall
      task (PSR), was reduced compared to the HC group at a standard interstimulus
      interval (ISI) (p = 0.002). When the individual's AB duration was then used to
      adjust the ISI on the PSR task to three relative ISI rates (Slow (2 * ltpp),
      Medium (ltpp) and Fast (1/2 * ltpp)), performance on the PSR task was affected by
      group, position and ISI and qualified by an ISI * position (p = 0.001) and a
      trend to a triple interaction (p = 0.054). There was main effect of group at all
      ISIs, but group * position interaction only at Slow ISI (p = 0.01). Our
      interpretation of the results is that absolute ISI, rather than ISI relative to
      AB duration, affected performance.

PMID- 28740824
TI  - Associations between daily living skills, cognition, and real-world functioning
      across stages of schizophrenia; a study with the Schizophrenia Cognition Rating
      Scale Japanese version.
AB  - Cognitive function is impaired in patients with schizophrenia-spectrum disorders,
      even in their prodromal stages. Specifically, the assessment of cognitive
      abilities related to daily-living functioning, or functional capacity, is
      important to predict long-term outcome. In this study, we sought to determine the
      validity of the Schizophrenia Cognition Rating Scale (SCoRS) Japanese version, an
      interview-based measure of cognition relevant to functional capacity (i.e. co
      primary measure). For this purpose, we examined the relationship of SCoRS scores
      with performance on the Brief Assessment of Cognition in Schizophrenia (BACS)
      Japanese version, a standard neuropsychological test battery, and the Social and
      Occupational Functioning Assessment Scale (SOFAS), an interview-based social
      function scale. Subjects for this study (n = 294) included 38 patients with first
      episode schizophrenia (FES), 135 with chronic schizophrenia (CS), 102 with at
      risk mental state (ARMS) and 19 with other psychiatric disorders with psychosis.
      SCoRS scores showed a significant relationship with SOFAS scores for the entire
      subjects. Also, performance on the BACS was significantly correlated with SCoRS
      scores. These associations were also noted within each diagnosis (FES, CS, ARMS).
      These results indicate the utility of SCoRS as a measure of functional capacity
      that is associated both with cognitive function and real-world functional outcome
      in subjects with schizophrenia-spectrum disorders.

PMID- 28740825
TI  - NMDAR hypofunction and somatostatin-expressing GABAergic interneurons and
      receptors: A newly identified correlation and its effects in schizophrenia.
AB  - This review investigates the association between N-methyl-d-Aspartate receptor
      (NMDAR) hypofunction and somatostatin-expressing GABAergic interneurons (SST +)
      and how it contributes to the cognitive deficits observed in schizophrenia (SZ).
      This is based on evidence that NMDAR antagonists caused symptoms resembling SZ in
      healthy individuals. NMDAR hypofunction in GABAergic interneurons results in the
      modulation of the cortical network oscillation, particularly in the gamma range
      (30-80 Hz). These gamma-band oscillation (GBO) abnormalities were found to lead
      to the cognitive deficits observed in the disorder. Postmortem mRNA studies have
      shown that SST decreased more significantly than any other biomarker in
      schizophrenic subjects. The functional role of Somatostatin (SST) in the
      aetiology of SZ can be studied through its receptors. Genetic knockout studies in
      animal models in Huntington's disease (HD) have shown that a specific SST
      receptor, SSTR2, is increased along with the increased NMDAR activity, with
      opposing patterns observed in SZ. A direct correlation between SSTR and NMDAR is
      hence inferred in this review with the hope of finding a potential new
      therapeutic target for the treatment of SZ and related neurological conditions.

PMID- 28740826
TI  - EPICOG-SCH: A brief battery to screen cognitive impact of schizophrenia in stable
      outpatients.
AB  - Brief batteries in schizophrenia, are needed to screen for the cognitive impact
      of schizophrenia. We aimed to validate and co-norm the Epidemiological Study of
      Cognitive Impairment in Schizophrenia (EPICOG-SCH) derived brief cognitive
      battery. A cross-sectional outpatient evaluation was conducted of six-hundred
      seventy-two patients recruited from 234 centers. The brief battery included well
      known subtests available worldwide that cover cognitive domains related to
      functional outcomes: WAIS-III-Letter-Number-Sequencing-LNS, Category Fluency Test
      CFT, Logical-Memory Immediate Recall-LM, and Digit-Symbol-Coding-DSC. CGI-SCH
      Severity and WHO-DAS-S were used to assess clinical severity and functional
      impairment, respectively. Unit Composite Score (UCS) and functional regression
      weighted Composite Scores (FWCS) were obtained; discriminant properties of FWCS
      to identify patients with different levels of functional disability were analyzed
      using receiver-operating characteristic (ROC) technique. The battery showed good
      internal consistency, Cronbach's alpha = 0.78. The differences between cognitive
      performance across CGI-SCH severity level subscales ranged from 0.5 to 1 SD.
      Discriminant capacity of the battery in identifying patients with up to moderate
      disability levels showed fair discriminant accuracy with areas under the curve
      (AUC) > 0.70, p < 0.0001. An FWCS mean cut-off score >= 100 showed likelihood
      ratios (LR) up to 4.7, with an LR + of 2.3 and a LR - of 0.5. An FWCS cut-off >=
      96 provided the best balance between sensitivity (0.74) and specificity (0.62).
      The EPICOG-SCH proved to be a useful brief tool to screen for the cognitive
      impact of schizophrenia, and its regression-weighted Composite Score was an
      efficient complement to clinical interviews for confirming patients' potential
      functional outcomes and can be useful for monitoring cognition during routine
      outpatient follow-up visits.

PMID- 28740827
TI  - Self versus informant reports on the specific levels of functioning scale:
      Relationships to depression and cognition in schizophrenia and schizoaffective
      disorder.
AB  - The goal of the current study was to examine the relationships between insight
      and both cognitive function and depression in schizophrenia and schizoaffective
      disorder, and to determine if there were similar relationships across diagnostic
      categories. We examined discrepancies between self and informant reports of
      function on the Specific levels of function scale as a metric of insight for
      interpersonal, social acceptance, work and activities. We examined two samples of
      individuals with schizophrenia and/or schizoaffective disorder (Ns of 188 and 67
      respectively). In Sample 1, cognition was measured using the Dot Probe Expectancy
      Task. In Sample 2, cognition was measured by averaging several subtests from the
      MATRICS consensus cognitive battery, as well as additional measures of working
      memory. In both samples, depression was measured using the Brief Psychiatric
      Rating Scale. In both samples, we found significant relationships between worse
      cognition and overestimations of work function, as well as between higher
      depression levels and underestimation of interpersonal function. These
      relationships were specific to interpersonal and work function, with
      significantly stronger correlations with interpersonal and work function compared
      to the other areas of function. Similar results were found across diagnostic
      categories. These results have important implications for treatment planning, as
      they suggest the need to take into account depression and cognitive function when
      evaluating the patient's self-report of function, and highlight the utility of
      informant reports in evaluating function and treatment planning. Further, they
      add to the literature on the similarity across schizophrenia and schizoaffective
      disorder in a variety of pathological mechanisms.

PMID- 28740828
TI  - Omega-3 fatty acids related to cognitive impairment in patients with
      schizophrenia.
AB  - Cognitive impairment is strongly associated with functional outcome in patients
      with schizophrenia but its pathophysiology remains largely unclear. Involvement
      of omega-3 fatty acids in the cognitive function of healthy individuals and
      patients with neuropsychiatric disease has received increasing attention. The aim
      of this study was to examine the relationship between omega-3 fatty acids with
      cognitive function, social function, and psychiatric symptoms in patients with
      schizophrenia. The subjects included 30 patients with schizophrenia or
      schizoaffective disorder. Psychiatric symptoms, cognitive function, and social
      function were assessed using the Positive and Negative Syndrome Scale, the Brief
      Assessment of Cognition in Schizophrenia (BACS), and the Social Functioning Scale
      (SFS), respectively. Blood serum omega-3 fatty acids were assessed using gas
      chromatography. The BACS composite score was significantly correlated with blood
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. In addition, a
      daily dose of antipsychotic medication was negatively and significantly
      correlated with the blood DHA level and with the BACS composite score. Step-wise
      multiple regression analyses demonstrated that the SFS score was significantly
      associated with the BACS composite score. Our results indicate that reduced blood
      omega-3 fatty acids are associated with cognitive impairment, which then impacts
      social functioning outcomes in schizophrenia.

PMID- 28740829
TI  - No association between symptom severity and MMN impairment in schizophrenia: A
      meta-analytic approach.
AB  - The mismatch negativity (MMN) is an event-related potential that is consistently
      attenuated in people with schizophrenia. Within the predictive coding model of
      psychosis, MMN impairment is thought to reflect the same prediction failures that
      are also thought to underlie the development and crystallization of delusions and
      hallucinations. However, the true relationship between symptom severity and MMN
      impairment across studies has not yet been established. The present meta-analysis
      used meta-regressions to examine the relationship between MMN impairment
      (quantified as Hedges' g) and PANSS positive and negative symptom totals across
      62 and 68 samples, respectively. Furthermore, we examined the relationship
      between MMN impairment and group differences in educational achievement (n = 47
      samples), cognitive ability (n = 36 samples), and age (n = 86 samples). Overall,
      we found no significant associations between MMN impairment and symptom severity
      (p's > 0.50); however, we did observe a trend-level association between MMN
      impairment and lower education (p = 0.07) and a significant association with
      older age (p < 0.01) in the schizophrenia patient group. Taken together, these
      results challenge a simple predictive coding model of psychosis, and suggest that
      MMN impairment may be more closely associated with premorbid functioning than
      with the expression of psychotic symptoms.

PMID- 28740830
TI  - Structure, Activity Regulation, and Role of the Mitochondrial Calcium Uniporter
      in Health and Disease.
AB  - Mitochondrial Ca2+ uptake plays a pivotal role both in cell energy balance and in
      cell fate determination. Studies on the role of mitochondrial Ca2+ signaling in
      pathophysiology have been favored by the identification of the genes encoding the
      mitochondrial calcium uniporter (MCU) and its regulatory subunits. Thus, research
      carried on in the last years on one hand has determined the structure of the MCU
      complex and its regulation, on the other has uncovered the consequences of
      dysregulated mitochondrial Ca2+ signaling in cell and tissue homeostasis. Whether
      mitochondrial Ca2+ uptake can be exploited as a weapon to counteract cancer
      progression is debated. In this review, we summarize recent research on the
      molecular structure of the MCU, the regulatory mechanisms that control its
      activity and its relevance in pathophysiology, focusing in particular on its role
      in cancer progression.

PMID- 28740831
TI  - The Impact of the Tumor Microenvironment on the Properties of Glioma Stem-Like
      Cells.
AB  - Glioblastoma is the most common and highly malignant primary brain tumor, and
      patients affected with this disease exhibit a uniformly dismal prognosis. Glioma
      stem-like cells (GSCs) are a subset of cells within the bulk tumor that possess
      self-renewal and multi-lineage differentiation properties similar to somatic stem
      cells. These cells also are at the apex of the cellular hierarchy and cause tumor
      initiation and expansion after chemo-radiation. These traits make them an
      attractive target for therapeutic development. Because GSCs are dependent on the
      brain microenvironment for their growth, and because non-tumorigenic cell types
      in the microenvironment can influence GSC phenotypes and treatment response, a
      better understanding of these cell types is needed. In this review, we provide a
      focused overview of the contributions from the microenvironment to GSC homing,
      maintenance, phenotypic plasticity, and tumor initiation. The interaction of GSCs
      with the vascular compartment, mesenchymal stem cells, immune system, and normal
      brain cell types are discussed. Studies that provide mechanistic insight into
      each of these GSC-microenvironment interactions are warranted in the future.

PMID- 28740832
TI  - Post-mortem examination in the United Kingdom: present and future.

PMID- 28740833
TI  - Gelatinous transformation of bone marrow.

PMID- 28740834
TI  - A second reported malignancy in a patient with Morquio syndrome.
AB  - Morquio syndrome is a rare lysosomal storage disease that affects multiple organ
      systems. However, it is rarely associated with malignancy. We present the case of
      a 30-year old man with Morquio syndrome associated with gastric adenocarcinoma.
      This case also demonstrates two other findings that have not been previously
      described in patients with Morquio syndrome - malrotation of brainstem and
      cerebellum, without clinical neurologic deficit, and persistence of fetal
      lobulation in the kidneys.

PMID- 28740835
TI  - Severe pulmonary hypertension due to combined pulmonary fibrosis and emphysema:
      another cause of death among smokers.
AB  - In 2005, the combined pulmonary fibrosis and emphysema (CPFE) was first defined
      as a distinct entity, which comprised centrilobular or paraseptal emphysema in
      the upper pulmonary lobes, and fibrosis in the lower lobes accompanied by reduced
      diffused capacity of the lungs for carbon monoxide (DLCO). Recently, the fibrosis
      associated with the connective tissue disease was also included in the diagnosis
      of CPFE, although the exposure to tobacco, coal, welding, agrochemical compounds,
      and tire manufacturing are the most frequent causative agents. This entity
      characteristically presents reduced DLCO with preserved lung volumes and severe
      pulmonary hypertension, which is not observed in emphysema and fibrosis alone. We
      present the case of a 63-year-old woman with a history of heavy tobacco smoking
      abuse, who developed progressive dyspnea, severe pulmonary hypertension, and cor
      pulmonale over a 2-year period. She attended the emergency facility several times
      complaining of worsening dyspnea that was treated as decompensate chronic
      obstructive pulmonary disease (COPD). The imaging examination showed paraseptal
      emphysema in the upper pulmonary lobes and fibrosis in the middle and lower
      lobes. The echo Doppler cardiogram revealed the dilation of the right cardiac
      chambers and pulmonary hypertension, which was confirmed by pulmonary trunk
      artery pressure measurement by catheterization. During this period, she was
      progressively restricted to the minimal activities of daily life and dependent on
      caregivers. She was brought to the hospital neurologically obtunded, presenting
      anasarca, and respiratory failure, which led her to death. The autopsy showed
      signs of pulmonary hypertension and findings of fibrosis and emphysema in the
      histological examination of the lungs. The authors highlight the importance of
      the recognition of this entity in case of COPD associated with severe pulmonary
      hypertension of unknown cause.

PMID- 28740836
TI  - Mycotic aneurysm with aortoduodenal fistula.
AB  - Firstly described in the 19th century by Sir William Osler, the mycotic aneurysm
      (MA) is a rare entity characterized by an abnormal arterial dilation, which is
      potentially fatal, and is associated with the infection of the vascular wall.
      Elderly patients are mostly involved, especially when risk factors like chronic
      diseases, immunosuppression, neoplasia, and arterial manipulation are associated.
      The authors report the case of a young male patient diagnosed with an aortic
      aneurysm of infectious origin in the presence of repeated negative blood
      cultures. The diagnostic hypothesis was raised when the patient was hospitalized
      for an inguinal hernia surgery. The diagnosis was confirmed based on imaging
      findings consistent with mycotic aneurism. The patient was treated with an
      endovascular prosthesis associated with a long-lasting antibiotic therapy. Five
      months later, the patient attended the emergency unit presenting an upper
      digestive hemorrhage and shock, from which he died. The autopsy revealed a huge
      aneurysm of the abdominal aorta with an aortoduodenal fistula. The histological
      examination of the arterial wall revealed a marked inflammatory process,
      extensive destruction of the arterial wall, and the presence of Gram-positive
      bacteria. This case highlights the atypical presentation of a MA associated with
      an aortoduodenal fistula. Besides the early age of the patient, no primary
      arterial disease could be found, and no source of infection was detected.

PMID- 28740837
TI  - Histological remission of autoimmune hepatitis after the addition of allopurinol
      and azathioprine dose reduction.
AB  - The standard therapy for some autoimmune diseases consists of a combination of
      corticosteroids and thiopurines. In non-responders to thiopurine drugs, the
      measurement of the metabolites of azathioprine, 6-thioguanine, and 6
      methylmercaptopurine, can be a useful tool. The measurement has been used during
      the treatment of inflammatory bowel diseases and, less commonly, in autoimmune
      hepatitis. Many patients preferentially metabolize thiopurines to 6
      methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6
      thioguanine, the active immunosuppressive metabolite. The addition of allopurinol
      shifts the metabolism of thiopurine towards 6-thioguanine, improving the
      immunosuppressive effect. We present the case of a 51-year-old female with
      autoimmune hepatitis who had a biochemical response after azathioprine and
      prednisone treatment without histological remission, and who preferentially
      shunted to 6-MMP. After the addition of allopurinol, the patient's 6-thioguanine
      levels increased, and she reached histological remission with a reduction of 67%
      of the original dose of azathioprine. The patient did not develop clinical
      manifestations as a consequence of her increased immunosuppressive state. We also
      review the relevant literature related to this issue. In conclusion, the addition
      of allopurinol to thiopurine seems to be an option for those patients who do not
      reach histological remission and who have a skewed thiopurine metabolite profile.

PMID- 28740838
TI  - A rare case of centronuclear myopathy with DNM2 mutation: genotype-phenotype
      correlation.
AB  - Centronuclear myopathy (CNM) is a group of rare genetic muscle disorders
      characterized by muscle fibers with centrally located nuclei. The most common
      forms of CNM have been attributed to X-linked recessive mutations in the MTM1
      gene; autosomal-dominant mutations in the DNM2 gene-encoding dynamin-2, the BIN1
      gene; and autosomal-recessive mutations in BIN1, RYR1, and TTN genes. Dominant
      CNM due to DNM2 mutations usually follows a mild clinical course with the onset
      in adolescence. Currently, around 35 mutations of the DNM2 gene have been
      identified in CNM; however, the underlying molecular mechanism of DNM2 mutation
      in the pathology of CNM remains elusive, and the standard clinical
      characteristics have not yet been defined. Here, we describe the case of a 17
      year-old female who presented with proximal muscle weakness along with congenital
      anomalous pulmonary venous connection (which has not been described in previous
      cases of CNM), scoliosis, and lung disease without a significant family history.
      Her creatine kinase level was normal. Histology, special stains, and electron
      microscope findings on her skeletal muscle biopsy showed CNM with the
      characteristic features of a DNM2 mutation, which was later confirmed by next
      generation sequencing. This case expands the known clinical and pathological
      findings of CNM with DNM2 gene mutation.

PMID- 28740839
TI  - Primary pelvic hydatid cyst in a postmenopausal female: a surgical challenge.
AB  - Primary pelvic hydatid cysts are a rare entity and are often overlooked as a
      differential diagnosis of a pelvic-space-occupying lesion particularly in non
      endemic regions. Unpreparedness and a hasty decision on the surgical approach may
      end in life-threatening complications and systemic dissemination of the disease.
      We report the case of a 55-year-old postmenopausal woman with a history of two
      previous unsuccessful surgeries to remove pelvic cystic lesions due to dense
      adhesions between the surrounding gut wall, bladder, and the cyst wall. Clinical
      and imaging findings failed to diagnose the nature of the cysts, and a laparotomy
      was contemplated. On the third surgical attempt, the clinical suspicion was
      considered and by meticulous dissection the cysts were removed thoroughly without
      undue complications. In the postoperative follow-up period there was no sign of
      disease recurrence or dissemination.

PMID- 28740840
TI  - Bicytopenia and leukoerythroblastosis: a rare initial presentation of signet ring
      cell gastric adenocarcinoma.
AB  - Gastric adenocarcinoma is a common neoplasia and is responsible for up to 30% of
      the overall deaths due to cancer. Advanced disease is mostly characterized by
      peritoneum, liver, and lung involvement. The spread of the disease to the bone is
      rare, and bone marrow dissemination is even rarer. In this setting,
      leukoerythroblastosis may be the initial manifestation of the disease. The
      authors report the case of a 64-year-old Caucasian man who sought medical care
      complaining of back pain, weakness, and weight loss. The physical examination
      revealed pallor, and the laboratory work-up depicted severe anemia and
      thrombocytopenia; the peripheral blood smear was consistent with
      leukoerythroblastosis. The ongoing investigation through a bone marrow biopsy
      showed massive involvement of the bone marrow by a signet ring cell
      adenocarcinoma. During hospitalization, the patient presented melena, and an
      upper digestive endoscopy depicted an ulcerated and infiltrative lesion in the
      cardia, upon which the histological examination revealed a signet ring cell
      adenocarcinoma. This case highlights the bone marrow invasion represented by
      bicytopenia and leukoerythroblastosis as the initial manifestation of this
      histological type of gastric cancer. Although treatment attempts were made with
      chemotherapy and radiotherapy, the patient died early on, showing the aggressive
      behavior of this form of tumoral presentation.

PMID- 28740841
TI  - Migrainous infarction: a rare and often overlooked diagnosis.
AB  - Migraine is a neurological entity and a well-known independent risk factor for
      cerebral infarction, which mostly afflicts the young female population.
      Researching focal neurological signs in this subset of the population with the
      diagnosis of a neurological ischemic event should always take into account the
      migraine as the etiology or as an associated factor. The etiology of central
      nervous system (CNS) ischemia is considerable. Migraine, although rare, also may
      be included in this vast etiological range, which is called migrainous
      infarction. In this setting, the diagnostic criteria required for this diagnosis
      is extensive. Herein, we present the case of a female adolescent who submitted to
      the emergency facility complaining of diplopia, dysarthria, and imbalance, which
      started concomitantly with a migrainous crisis with aura-a challenging clinical
      case that required extensive research to address all possible differential
      diagnoses.

PMID- 28740842
TI  - Reconstruction of the skull inverting the deformed surface of the bone after
      exeresis of a frontal arachnoid cyst.
AB  - Intracranial arachnoid cysts need to be operated on when they are causing
      symptoms and aesthetic problems. The aim of this case report was to describe a
      new method of reconstructing the skull by eliminating a left frontal bone
      deformity by turning the inside out and the outside inward, which provided good
      aesthetics and protected the region of surgical interest after the removal of an
      arachnoid cyst of the left frontal lobe.

PMID- 28740843
TI  - Comparative Readability Analysis of Online Patient Education Resources on
      Inflammatory Bowel Diseases.
AB  - BACKGROUND: The National Institutes of Health recommend a readability grade level
      of less than 7th grade for patient directed information. In this study, we use
      validated readability metrics to analyze patient information from prominent
      websites pertaining to ulcerative colitis and Crohn's disease. METHODS: The terms
      "Crohn's Disease," "Ulcerative Colitis," and "Inflammatory Bowel Disease" were
      queried on Google and Bing. Websites containing patient education material were
      saved as a text file and then modified through expungement of medical terminology
      that was described within the text. Modified text was then divided into
      subsections that were analyzed using six validated readability scales. RESULTS:
      None of the websites analyzed in this study achieved an estimated reading grade
      level below the recommended 7th grade. The median readability grade level (after
      modification) was 11.5 grade levels for both Crohn's disease and ulcerative
      colitis. The treatment subsection required the highest level of education with a
      median readability grade of 12th grade (range of 6.9 to 17). CONCLUSION:
      Readability of online patient education material from the analyzed popular
      websites far exceeds the recommended level of being less than 7th grade. Patient
      education resources should be revised to achieve wider health literacy.

PMID- 28740844
TI  - Corrigendum: Monitoring Cerebral Oxygenation in Neonates: An Update.
AB  - [This corrects the article on p. 46 in vol. 5, PMID: 28352624.].

PMID- 28740845
TI  - Perspectives on a US-Mexico Border Community's Diabetes and "Health-Care" Access
      Mobilization Efforts and Comparative Analysis of Community Health Needs over 12
      Years.
AB  - This paper describes a community coalition-university partnership to address
      health needs in an underserved US-Mexico border, community. For approximately 15
      years, this coalition engaged in community-based participatory research with
      community organizations, state/local health departments, and the state's only
      accredited college of public health. Notable efforts include the systematic
      collection of health-relevant data 12 years apart and data that spawned numerous
      health promotion activities. The latter includes specific evidence-based chronic
      disease-preventive interventions, including one that is now disseminated and
      replicated in Latino communities in the US and Mexico, and policy-level changes.
      Survey data to evaluate changes in a range of health problems and needs, with a
      specific focus on those related to diabetes and access to health-care issues
      identified early on in the coalition as critical health problems affecting the
      community-are presented. Next steps for this community and lessons learned that
      may be applicable to other communities are discussed.

PMID- 28740846
TI  - The Transmission Chain Analysis of 2014-2015 Ebola Virus Disease Outbreak in
      Koinadugu District, Sierra Leone: An Observational Study.
AB  - INTRODUCTION: Sierra Leone experienced an unprecedented Ebola virus disease (EVD)
      outbreak in all its districts. Koinadugu District was the last to report an EVD
      case. Several outbreak response strategies were implemented. As part of lessons
      learnt, we conducted an observational study to describe the transmission chain in
      the district and the impact of the control measures implemented to contain the
      outbreak. METHODS: We reconstructed the transmission chain, positioning both
      confirmed and probable cases, described the distribution of the EVD confirmed
      cases in the context of the routes of transmission (Community, Funeral or Health
      facility setting) and assessed the impact of control measures using the
      surveillance data collected during the outbreak. RESULTS: All 142 confirmed and
      probable EVD cases registered were fully resolved in the transmission chain.
      72.5% of all the EVD cases in the district were exposed in the community, 26.1%
      exposed during funerals, and 1.4% exposed in the health facility setting. Health
      care workers contributed little to the EVD outbreak. 71.1% of EVD transmission
      occurred among family members. Female EVD cases generated more secondary cases
      than their male counterparts (P = 0.03). With removal of EVD cases from the
      community and admission to the community care center (CCC), the EVD transmission
      in the community decreased to substantially lower rates. In addition,
      transmission due to exposure in health facilities was further reduced with the
      implementation of full infection and prevention controls. CONCLUSION: This study
      details the transmission chain of EVD in a rural district setting and the public
      health interventions implemented to successfully limit the outbreak to just one
      of 11 chiefdoms. Heightened community-based surveillance for early case
      detection, swift isolation of suspect cases, efficient contact tracing and
      monitoring, and good infection prevention and control measures in health
      facilities were highly effective in limiting transmission and, eventually,
      breaking the transmission chain. CCCs were also instrumental in achieving early
      isolation and basic care for suspect cases, while ensuring that their family
      members who were close contacts remained in the community for easy contact
      tracing and monitoring. These were very useful lessons learnt that would inform
      the management of future outbreaks.

PMID- 28740847
TI  - Fournier's Gangrene: Lessons Learned from Multimodal and Multidisciplinary
      Management of Perineal Necrotizing Fasciitis.
AB  - BACKGROUND: Fournier's gangrene (FG) is a rapidly evolving necrotizing fasciitis
      of the perineum and the genital area, the scrotum as it most commonly affects man
      in the vast majority of cases. It is polymicrobial in origin, due to the
      synergistic action of anaerobes and aerobes and has a very high mortality. There
      are many predisposing factors including diabetes mellitus, alcoholism,
      immunosuppression, renal, and hepatic disease. The prognosis of the disease
      depends on a lot of factors including but not limited to patient age, disease
      extent, and comorbidities. The purpose of the study is to describe the experience
      of a general surgery department in the management of FG, to present the
      multimodal and multidisciplinary treatment of the disease, to identify predictors
      of mortality, and to make general surgeons familiar with the disease. METHODS:
      The current retrospective study is presenting the experience of our general
      surgery department in the management of FG during the last 20 years. The clinical
      presentation and demographics of the patients were recorded. Also we recorded the
      laboratory data, the comorbidities, the etiology, and microbiology and the
      therapeutic interventions performed, and we calculated the various severity
      indexes. Patients were divided to survivors and non-survivors, and all the
      collected data were statistically analyzed to assess mortality factors using
      univariate and then multivariate analysis. RESULTS: In our series, we treated a
      total of 24 patients with a mean age 58.9 years including 20 males (83.4%) and 4
      females (16.6%). In most patients, a delay between disease onset and seeking of
      medical help was noted. Comorbidities were present in almost all patients
      (87.5%). All patients were submitted to extensive surgical debridements and
      received broad-spectrum antibiotics until microbiological culture results were
      received. Regarding all the collected data, there was no statistically
      significant difference between survivors and non-survivors except the presence of
      malignancy in non-survivors (p = 0.036) and the lower hemoglobin (p < 0.001) and
      hematocrit (p = 0.002) in non-survivors. However, multivariate analysis did not
      reveal any predictor of mortality. CONCLUSION: Early diagnosis, aggressive
      thorough surgical treatment, and administration of the proper antibiotic
      treatment comprise the cornerstone for the outcome of this disease. In small
      populations like in the present study, it is difficult to recognize any
      predictors of mortality and even the severity indexes, which take into account a
      lot of data cannot predict mortality.

PMID- 28740848
TI  - Patient Characteristics and Clinical Outcomes with Low-Dose Dabigatran.
AB  - BACKGROUND/AIMS: Dabigatran, an oral direct thrombin inhibitor, is used in
      patients with non-valvular atrial fibrillation to reduce thromboembolic events.
      Whereas the 150 mg dosing regimen has been extensively studied in clinical
      setting, to date, there is no clinical data on the 75 mg (low dose, "LD")
      regimen. In this study, we evaluated patient characteristics and clinical
      outcomes in 49 patients treated with LD dabigatran. METHODS: Electronic medical
      records were utilized to compare patients from one medical center treated with LD
      dabigatran to those from the warfarin arm of the RE-LY trial. RESULTS: Compared
      to those from the warfarin arm of the RE-LY trial, the LD dabigatran patients
      were significantly older (82.6 vs. 71.6 years, p < 0.001), had higher prevalence
      of diabetes (42.9 vs. 23%, p < 0.001), were predominantly male (100 vs. 63.3%, p
      < 0.001), and had higher CHADS2 score (2.8 vs. 2.1, p < 0.001). Only 9 (18%)
      patients had creatinine clearance of <30 ml/min and none were on concomitant
      medications that required dose adjustment to LD dabigatran. During a mean follow
      up of 10.1 months, there were no thromboembolic events, no cerebrovascular
      events, and seven bleeding events in the LD dabigatran group of which only two
      required blood transfusion. CONCLUSION: In this database, most patients received
      LD dabigatran based on characteristics not related to the approved indications
      for this dose. The exploratory clinical outcomes of using LD dabigatran outside
      of the current approved indications are promising in this high-risk population
      and deserve further investigation to better understand the role of LD dabigatran
      in clinical practice.

PMID- 28740849
TI  - End-Cycle Sow Carcass Condemnation in a French Slaughterhouse.
AB  - Surveillance at an abattoir allows all animals or carcasses that present a
      potential public health risk to be withdrawn from the human food chain. Whole
      carcass condemnation results in important economic losses, not only for the
      producer but also for other participants in the meat industry. Access to the
      personal electronic database of an abattoir in France enabled us to run logistic
      regression models to investigate the risk factors for whole-carcass condemnation
      of end-cycle sows in that abattoir. When end-cycle sows that were slaughtered and
      eviscerated between 22 June 2015 and 8 December 2015 (185 days) were considered
      (n = 19,866), the results highlighted the importance of the total theoretical
      time off feed, which represents the fasting period from leaving the farm of
      origin to the time of slaughter (including transportation and waiting time at the
      abattoir). Each 10-h increase in the theoretical time off feed was associated
      with a 31% greater likelihood of whole-carcass condemnation [odd ratio (OR) =
      1.31, CI 95% (1.27; 1.34)], and a 10 kg increase in carcass weight before
      refrigeration was associated with a 23% lower likelihood of carcass condemnation
      [OR = 0.77, CI 95% (0.75; 0.78)]. The results also indicate the importance of the
      producer group that the farmer belonged to (P < 0.01). A relatively small number
      of variables was available in the actual database to study the relevant risk
      factors for whole-carcass condemnation associated with or without diseases at the
      farm of origin. This derives partly from the fact that traceability at the
      abattoir in France is done per batch rather than individually for pigs; further,
      limited information is available at the farm level. An investigation of the
      reasons for whole-carcass condemnation could have been informative; however, it
      was not feasible in a reasonable timeframe because these data were not saved in a
      database in a systematic way. Some of the difficulties encountered in this study
      should soon be alleviated by using the meat inspection information system
      software for collecting livestock meat inspection data. Implemented recently by
      the French ministry of agriculture, this new tool should allow for broader
      perspectives in swine surveillance.

PMID- 28740851
TI  - Burden of Misconception in Sexual Health Care Setting: A Cross-Sectional
      Investigation among the Patients Attending a Psychiatric Sex Clinic of
      Bangladesh.
AB  - BACKGROUND: Bangladesh is a country in South Asia with about 160 million people
      and achieved health related Millennium Development Goals (MDG) significantly. But
      sexual health is still an untapped issue with predominant myths and
      misconception. OBJECTIVE: We aimed to look into the proportions of patients
      attending sexual health care services due to misconceptions. METHODS: The
      descriptive, cross-sectional study was conducted among 110 patients attending
      Psychiatric Sex Clinic (PSC) of Bangabandhu Sheikh Mujib Medical University.
      Respondents were included in the study with convenient sampling from November
      2016 to March 2017. Data were collected through face-to-face interview with
      semistructured preformed, pretested questionnaire and analyzed by SPSS software
      16.0 version. RESULTS: Most of the patients (93%) were male, 60% were married,
      62% were urban habitant, 42% were under grade 10, and 33% were service holder.
      Total 55% of the patients had misconceptions and 29% visited only for
      misconception; 14% had Premature Ejaculation; and 12% had desire disorder. 32% of
      the patients had psychiatric disorders and among them depression was most common,
      13%. CONCLUSION: Positive openness in sexual health and appropriate strategy
      should be taken to improve the quality of sexual life as well as reduce the
      misconception in the people of Bangladesh.

PMID- 28740850
TI  - The Role of Dog Population Management in Rabies Elimination-A Review of Current
      Approaches and Future Opportunities.
AB  - Free-roaming dogs and rabies transmission are integrally linked across many low
      income countries, and large unmanaged dog populations can be daunting to rabies
      control program planners. Dog population management (DPM) is a multifaceted
      concept that aims to improve the health and well-being of free-roaming dogs,
      reduce problems they may cause, and may also aim to reduce dog population size.
      In theory, DPM can facilitate more effective rabies control. Community engagement
      focused on promoting responsible dog ownership and better veterinary care could
      improve the health of individual animals and dog vaccination coverage, thus
      reducing rabies transmission. Humane DPM tools, such as sterilization, could
      theoretically reduce dog population turnover and size, allowing rabies
      vaccination coverage to be maintained more easily. However, it is important to
      understand local dog populations and community attitudes toward them in order to
      determine whether and how DPM might contribute to rabies control and which DPM
      tools would be most successful. In practice, there is very limited evidence of
      DPM tools achieving reductions in the size or turnover of dog populations in
      canine rabies-endemic areas. Different DPM tools are frequently used together and
      combined with rabies vaccinations, but full impact assessments of DPM programs
      are not usually available, and therefore, evaluation of tools is difficult.
      Surgical sterilization is the most frequently documented tool and has
      successfully reduced dog population size and turnover in a few low-income
      settings. However, DPM programs are mostly conducted in urban settings and are
      usually not government funded, raising concerns about their applicability in
      rural settings and sustainability over time. Technical demands, costs, and the
      time necessary to achieve population-level impacts are major barriers. Given
      their potential value, we urgently need more evidence of the effectiveness of DPM
      tools in the context of canine rabies control. Cheaper, less labor-intensive
      tools for dog sterilization will be extremely valuable in realizing the potential
      benefits of reduced population turnover and size. No one DPM tool will fit all
      situations, but if DPM objectives are achieved dog populations may be stabilized
      or even reduced, facilitating higher dog vaccination coverages that will benefit
      rabies elimination efforts.

PMID- 28740852
TI  - Body Posture, Postural Stability, and Metabolic Age in Patients with Parkinson's
      Disease.
AB  - BACKGROUND: The study aims to analyze the relationship between body posture and
      composition, as well as postural stability in Parkinson's disease patients.
      MATERIAL AND METHODS: 32 people were evaluated. The study was conducted in the
      Laboratory of Posturology at Jan Kochanowski University in Kielce (Poland). Body
      posture was examined using the optoelectronic body posture Formetric Diers Method
      III 4D. Postural stability was evaluated using the Biodex Balance System
      platform. Body composition was assessed with the method of bioelectrical
      impedance analysis using the Tanita MC 780 MA analyzer. RESULTS: 11 patients
      (34.37%) had hyperkyphosis, 10 (31.25%) hyperlordosis, and 3 (9.37%)
      hyperkyphosis-hyperlordosis posture. Scoliosis (>10 degrees ) was observed in 28
      (87.5%) subjects, whereas 4 (12.5%) presented scoliotic body posture (1-9 degrees
      ). In the examined population, all parameters of postural stability were within
      normal limits. CONCLUSIONS: A significant positive correlation was observed
      between surface rotation ( degrees ), General Stability Index (r = 0.4075, p =
      0.0206), and Anteroposterior Stability Index (r = 0.3819, p = 0.0310). There was
      also a significant positive correlation between surface rotation (+max) ( degrees
      ), General Stability Index (r = 0.3526, p = 0.0206), and Anteroposterior
      Stability Index (r = 0.3873, p = 0.0285). Metabolic age also presented a
      significant positive correlation between metabolic age and General Stability
      Index (r = 0.4057, p = 0.0212), as well as Anteroposterior Stability Index (r =
      0.3507, p = 0.0490).

PMID- 28740853
TI  - Prothrombotic Fibrin Clot Phenotype in Patients with Deep Vein Thrombosis and
      Pulmonary Embolism: A New Risk Factor for Recurrence.
AB  - Prothrombotic fibrin clot phenotype, involving faster formation of dense meshwork
      composed of thinner and highly branched fibers that are relatively resistant to
      plasmin-induced lysis, has been reported in patients with not only myocardial
      infarction or stroke, but also venous thromboembolism (VTE), encompassing deep
      vein thrombosis (DVT), and/or pulmonary embolism (PE). Prothrombotic fibrin clot
      phenotype, in particular prolonged clot lysis time, is considered a novel risk
      factor for VTE as well as venous thrombosis at unusual location, for example,
      cerebral sinus venous thrombosis, retinal vein obstruction, and Budd-Chiari
      syndrome. Growing evidence from observational studies indicates that abnormal
      fibrin clot properties can predict recurrent DVT and PE and they are involved in
      serious complications of VTE, for example, thromboembolic pulmonary hypertension
      and postthrombotic syndrome. The purpose of this article is to review our current
      understanding of the role of fibrin clot structure and function in venous
      thrombosis with emphasis on clinical issues ranging from prognosis to therapy.

PMID- 28740854
TI  - Clinical Implications of Oscillatory Lung Function during Methacholine
      Bronchoprovocation Testing of Preschool Children.
AB  - OBJECTIVE: To investigate the repeatability and safety of measuring impulse
      oscillation system (IOS) parameters and the point of wheezing during
      bronchoprovocation testing of preschool children. METHODS: Two sets of
      methacholine challenge were conducted in 36 asthma children. The test was
      discontinued if there was a significant change in reactance (Xrs5) and resistance
      (Rrs5) at 5 Hz (Condition 1) or respiratory distress due to airway obstruction
      (Condition 2). The repeatability of PC80_Xrs5, PC30_Rrs5, and wheezing (PCw) was
      assessed. The changes in Z-scores and SD-indexes from prebaseline (before
      testing) to postbaseline (after bronchodilator) were determined. RESULTS: For
      PC30_Rrs5, PC80_Xrs5, and PCw for subjects, PC80_Xrs5 showed the highest
      repeatability. Fifteen of 70 tests met Condition 2. The changes from pre- and
      postbaseline values varied significantly for Rrs5 and Xrs5. Excluding subjects
      with Z-scores higher than 2SD, we were able to detect 97.1% of bronchial
      hyperresponsiveness during methacholine challenge based on the change in Rrs5 or
      Xrs5. A change in IOS parameters was associated with wheezing at all frequencies.
      CONCLUSION: Xrs5 and Rrs5 have repeatability comparable with FEV1, and Xrs5 is
      more reliable than Rrs5. Clinicians can safely perform a challenge test by
      measuring the changes in Rrs5, Xrs5, and Z-scores from the prebaseline values.

PMID- 28740855
TI  - Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating
      Nrf2-Dependent Antioxidant Proteins.
AB  - We have shown earlier that pretreatment of cultured cells with aldose reductase
      (AR) inhibitors prevents hyperglycemia-induced mitogenic and proinflammatory
      responses. However, the effects of AR inhibitors on Nrf2-mediated anti
      inflammatory responses have not been elucidated yet. We have investigated how AR
      inhibitor fidarestat protects high glucose- (HG-) induced cell viability changes
      by increasing the expression of Nrf2 and its dependent phase II antioxidant
      enzymes. Fidarestat pretreatment prevents HG (25 mM)-induced Thp1 monocyte
      viability. Further, treatment of Thp1 monocytes with fidarestat caused a time
      dependent increase in the expression as well as the DNA-binding activity of Nrf2.
      In addition, fidarestat augmented the HG-induced Nrf2 expression and activity and
      also upregulated the expression of Nrf2-dependent proteins such as hemeoxygenase
      1 (HO1) and NQO1 in Thp1 cells. Similarly, treatment with AR inhibitor also
      induced the expression of Nrf2 and HO1 in STZ-induced diabetic mice heart and
      kidney tissues. Further, AR inhibition increased the HG-induced expression of
      antioxidant enzymes such as SOD and catalase and activation of AMPK-alpha1 in
      Thp1 cells. Our results thus suggest that pretreatment with AR inhibitor prepares
      the monocytes against hyperglycemic stress by overexpressing the Nrf2-dependent
      antioxidative proteins.

PMID- 28740856
TI  - Opsoclonus-Myoclonus Syndrome during Rituximab Treatment for Autoimmune Autonomic
      Ganglionopathy.

PMID- 28740857
TI  - H2S Loss through NalophanTM Bags: Contributions of Adsorption and Diffusion.
AB  - Hydrogen-sulfide (H2S) is a molecule of small dimensions typically present in the
      odor emissions from different plants. The European Standard EN 13725:2003 set a
      maximum storage time allowed of 30 hours, during which the sampling bag has to
      maintain the mixture of odorants with minimal changes. This study investigates
      the H2S losses through Nalophan bags and it shows that nonnegligible losses of
      H2S can be observed. The percent H2S loss after 30 hrs with respect to the
      initial concentration is equal to 33%  +/- 3% at a relative humidity of 20% and
      equal to 22%  +/- 1% at a relative humidity of 60%. The average quantity of
      adsorbed H2S at 30 h is equal to 2.17 105 gH2S/gNalophan at a storage humidity of
      20% and equal to 1.79 105 gH2S/gNalophan at a storage humidity of 60%. The
      diffusion coefficients of H2S through Nalophan, for these two humidity conditions
      tested, are comparable (i.e., 7.5 10-12 m2/sec at 20% humidity and 6.6 10-12
      m2/sec at 60% humidity).

PMID- 28740858
TI  - S-100beta and Antioxidant Capacity in Cerebrospinal Fluid during and after
      Thoracic Endovascular Aortic Repair.
AB  - BACKGROUND: Thoracic Endovascular Aortic Repair (TEVAR) has substantially
      decreased the mortality and major complications from aortic surgery. However,
      neurological complications such as spinal cord ischemia may still occur after
      TEVAR. S-100beta is a biomarker of central nervous system injury, and oxidant
      injury plays an important role in neurological injury. In this pilot study, we
      examined the trends of S-100beta and antioxidant capacity in the CSF during and
      after TEVAR. METHODS: We recruited 10 patients who underwent elective TEVAR. CSF
      samples were collected through a lumbar catheter at the following time points:
      before the start of surgery (T0) and immediately (T1) and 24 (T2) and 48 hours
      (T3) after the deployment of the aortic stent. S-100beta and CSF antioxidant
      capacity were analyzed with the use of commercially available kits. RESULTS: We
      observed that the level of S-100beta in all of the subjects at 24 hours after the
      deployment of the aortic stent (T2) increased. However, the levels of S-100beta
      at T1 and T3 were comparable to the baseline value. The antioxidant capacity
      remained unchanged. No patient had a clinical neurologic complication.
      CONCLUSIONS: Our observations may indicate biochemical/subclinical central
      nervous system injury attributable to the deployment of the aortic stent.

PMID- 28740859
TI  - Many Handicaps and a Lot of Good Luck. A Scientific Autobiography.

PMID- 28740860
TI  - Tunable and laser-reconfigurable 2D heterocrystals obtained by epitaxial stacking
      of crystallographically incommensurate Bi2Se3 and MoS2 atomic layers.
AB  - Vertical stacking is widely viewed as a promising approach for designing advanced
      functionalities using two-dimensional (2D) materials. Combining
      crystallographically commensurate materials in these 2D stacks has been shown to
      result in rich new electronic structure, magnetotransport, and optical
      properties. In this context, vertical stacks of crystallographically
      incommensurate 2D materials with well-defined crystallographic order are a
      counterintuitive concept and, hence, fundamentally intriguing. We show that
      crystallographically dissimilar and incommensurate atomically thin MoS2 and
      Bi2Se3 layers can form rotationally aligned stacks with long-range
      crystallographic order. Our first-principles theoretical modeling predicts
      heterocrystal electronic band structures, which are quite distinct from those of
      the parent crystals, characterized with an indirect bandgap. Experiments reveal
      striking optical changes when Bi2Se3 is stacked layer by layer on monolayer MoS2,
      including 100% photoluminescence (PL) suppression, tunable transmittance edge
      (1.1->0.75 eV), suppressed Raman, and wide-band evolution of spectral
      transmittance. Disrupting the interface using a focused laser results in a marked
      the reversal of PL, Raman, and transmittance, demonstrating for the first time
      that in situ manipulation of interfaces can enable "reconfigurable" 2D materials.
      We demonstrate submicrometer resolution, "laser-drawing" and "bit-writing," and
      novel laser-induced broadband light emission in these heterocrystal sheets.

PMID- 28740861
TI  - Global conditions in the solar corona from 2010 to 2017.
AB  - Through reduction of a huge data set spanning 2010-2017, we compare mean global
      changes in temperature, emission measure (EM), and underlying photospheric
      magnetic field of the solar corona over most of the last activity cycle. The
      quiet coronal mean temperature rises from 1.4 to 1.8 MK, whereas EM increases by
      almost a factor of 50% from solar minimum to maximum. An increased high
      temperature component near 3 MK at solar maximum drives the increase in quiet
      coronal mean temperature, whereas the bulk of the plasma remains near 1.6 MK
      throughout the cycle. The mean, spatially smoothed magnitude of the quiet Sun
      magnetic field rises from 1.6 G in 2011 to peak at 2.0 G in 2015. Active region
      conditions are highly variable, but their mean remains approximately constant
      over the cycle, although there is a consistent decrease in active region high
      temperature emission (near 3 MK) between the peak of solar maximum and present.
      Active region mean temperature, EM, and magnetic field magnitude are highly
      correlated. Correlation between sunspot/active region area and quiet coronal
      conditions shows the important influence of decaying sunspots in driving global
      changes, although we find no appreciable delay between changes in active region
      area and quiet Sun magnetic field strength. The hot coronal contribution to
      extreme ultraviolet (EUV) irradiance is dominated by the quiet corona throughout
      most of the cycle, whereas the high variability is driven by active regions.
      Solar EUV irradiance cannot be predicted accurately by sunspot index alone,
      highlighting the need for continued measurements.

PMID- 28740862
TI  - Giant convecting mud balls of the early solar system.
AB  - Carbonaceous asteroids may have been the precursors to the terrestrial planets,
      yet despite their importance, numerous attempts to model their early solar system
      geological history have not converged on a solution. The assumption has been that
      hydrothermal alteration was occurring in rocky asteroids with material properties
      similar to meteorites. However, these bodies would have accreted as a high
      porosity aggregate of igneous clasts (chondrules) and fine-grained primordial
      dust, with ice filling much of the pore space. Short-lived radionuclides melted
      the ice, and aqueous alteration of anhydrous minerals followed. However, at the
      moment when the ice melted, no geological process had acted to lithify this
      material. It would have been a mud, rather than a rock. We tested the effect of
      removing the assumption of lithification. We find that if the body accretes
      unsorted chondrules, then large-scale mud convection is capable of producing a
      size-sorted chondrule population (if the body accretes an aerodynamically sorted
      chondrule population, then no further sorting occurs). Mud convection both
      moderates internal temperature and reduces variation in temperature throughout
      the object. As the system is thoroughly mixed, soluble elements are not
      fractionated, preserving primitive chemistry. Isotopic and redox heterogeneity in
      secondary phases over short length scales is expected, as individual particles
      experience a range of temperature and water-rock histories until they are brought
      together in their final configuration at the end of convection. These results are
      consistent with observations from aqueously altered meteorites (CI and CM
      chondrites) and spectra of primitive asteroids. The "mudball" model appears to be
      a general solution: Bodies spanning a *1000 mass range show similar behavior.

PMID- 28740863
TI  - A nanosecond time-resolved XFEL analysis of structural changes associated with CO
      release from cytochrome c oxidase.
AB  - Bovine cytochrome c oxidase (CcO), a 420-kDa membrane protein, pumps protons
      using electrostatic repulsion between protons transferred through a water channel
      and net positive charges created by oxidation of heme a (Fe a ) for reduction of
      O2 at heme a3 (Fe a3). For this process to function properly, timing is
      essential: The channel must be closed after collection of the protons to be
      pumped and before Fe a oxidation. If the channel were to remain open, spontaneous
      backflow of the collected protons would occur. For elucidation of the channel
      closure mechanism, the opening of the channel, which occurs upon release of CO
      from CcO, is investigated by newly developed time-resolved x-ray free-electron
      laser and infrared techniques with nanosecond time resolution. The opening
      process indicates that CuB senses completion of proton collection and binds O2
      before binding to Fe a3 to close the water channel using a conformational relay
      system, which includes CuB, heme a3, and a transmembrane helix, to block backflow
      of the collected protons.

PMID- 28740864
TI  - Metal nanoparticle film-based room temperature Coulomb transistor.
AB  - Single-electron transistors would represent an approach to developing less power
      consuming microelectronic devices if room temperature operation and industry
      compatible fabrication were possible. We present a concept based on stripes of
      small, self-assembled, colloidal, metal nanoparticles on a back-gate device
      architecture, which leads to well-defined and well-controllable transistor
      characteristics. This Coulomb transistor has three main advantages. By using the
      scalable Langmuir-Blodgett method, we combine high-quality chemically synthesized
      metal nanoparticles with standard lithography techniques. The resulting
      transistors show on/off ratios above 90%, reliable and sinusoidal Coulomb
      oscillations, and room temperature operation. Furthermore, this concept allows
      for versatile tuning of the device properties such as Coulomb energy gap and
      threshold voltage, as well as period, position, and strength of the oscillations.

PMID- 28740865
TI  - Superconductivity across Lifshitz transition and anomalous insulating state in
      surface K-dosed (Li0.8Fe0.2OH)FeSe.
AB  - In iron-based superconductors, understanding the relation between
      superconductivity and electronic structure upon doping is crucial for exploring
      the pairing mechanism. Recently, it was found that, in iron selenide (FeSe),
      enhanced superconductivity (Tc of more than 40 K) can be achieved via electron
      doping, with the Fermi surface only comprising M-centered electron pockets. By
      using surface K dosing, scanning tunneling microscopy/spectroscopy, and angle
      resolved photoemission spectroscopy, we studied the electronic structure and
      superconductivity of (Li0.8Fe0.2OH)FeSe in the deep electron-doped regime. We
      find that a Gamma-centered electron band, which originally lies above the Fermi
      level (EF), can be continuously tuned to cross EF and contribute a new electron
      pocket at Gamma. When this Lifshitz transition occurs, the superconductivity in
      the M-centered electron pocket is slightly suppressed, and a possible
      superconducting gap with a small size (up to ~5 meV) and a dome-like doping
      dependence is observed on the new Gamma electron pocket. Upon further K dosing,
      the system eventually evolves into an insulating state. Our findings provide new
      clues to understand superconductivity versus Fermi surface topology and the
      correlation effect in FeSe-based superconductors.

PMID- 28740866
TI  - Distinct properties of the triplet pair state from singlet fission.
AB  - Singlet fission, the conversion of a singlet exciton (S1) to two triplets (2 *
      T1), may increase the solar energy conversion efficiency beyond the Shockley
      Queisser limit. This process is believed to involve the correlated triplet pair
      state 1(TT). Despite extensive research, the nature of the 1(TT) state and its
      spectroscopic signature remain actively debated. We use an end-connected
      pentacene dimer (BP0) as a model system and show evidence for a tightly bound
      1(TT) state. It is characterized in the near-infrared (IR) region (~1.0 eV) by a
      distinct excited-state absorption (ESA) spectral feature, which closely resembles
      that of the S1 state; both show vibronic progressions of the aromatic ring
      breathing mode. We assign these near-IR spectra to 1(TT)->Sn and S1->Sn'
      transitions; Sn and Sn' likely come from the antisymmetric and symmetric linear
      combinations, respectively, of the S2 state localized on each pentacene unit in
      the dimer molecule. The 1(TT)->Sn transition is an indicator of the intertriplet
      electronic coupling strength, because inserting a phenylene spacer or twisting
      the dihedral angle between the two pentacene chromophores decreases the
      intertriplet electronic coupling and diminishes this ESA peak. In addition to
      spectroscopic signature, the tightly bound 1(TT) state also shows chemical
      reactivity that is distinctively different from that of an individual T1 state.
      Using an electron-accepting iron oxide molecular cluster [Fe8O4] linked to the
      pentacene or pentacene dimer (BP0), we show that electron transfer to the cluster
      occurs efficiently from an individual T1 in pentacene but not from the tightly
      bound 1(TT) state. Thus, reducing intertriplet electronic coupling in 1(TT) via
      molecular design might be necessary for the efficient harvesting of triplets from
      intramolecular singlet fission.

PMID- 28740867
TI  - Fluorinated h-BN as a magnetic semiconductor.
AB  - We report the fluorination of electrically insulating hexagonal boron nitride (h
      BN) and the subsequent modification of its electronic band structure to a wide
      bandgap semiconductor via introduction of defect levels. The electrophilic nature
      of fluorine causes changes in the charge distribution around neighboring nitrogen
      atoms in h-BN, leading to room temperature weak ferromagnetism. The observations
      are further supported by theoretical calculations considering various possible
      configurations of fluorinated h-BN structure and their energy states. This
      unconventional magnetic semiconductor material could spur studies of stable two
      dimensional magnetic semiconductors. Although the high thermal and chemical
      stability of h-BN have found a variety of uses, this chemical functionalization
      approach expands its functionality to electronic and magnetic devices.

PMID- 28740868
TI  - Climate warming promotes species diversity, but with greater taxonomic
      redundancy, in complex environments.
AB  - Climate warming is predicted to alter species interactions, which could
      potentially lead to extinction events. However, there is an ongoing debate
      whether the effects of warming on biodiversity may be moderated by biodiversity
      itself. We tested warming effects on soil nematodes, one of the most diverse and
      abundant metazoans in terrestrial ecosystems, along a gradient of environmental
      complexity created by a gradient of plant species richness. Warming increased
      nematode species diversity in complex (16-species mixtures) plant communities (by
      ~36%) but decreased it in simple (monocultures) plant communities (by ~39%)
      compared to ambient temperature. Further, warming led to higher levels of
      taxonomic relatedness in nematode communities across all levels of plant species
      richness. Our results highlight both the need for maintaining species-rich plant
      communities to help offset detrimental warming effects and the inability of
      species-rich plant communities to maintain nematode taxonomic distinctness when
      warming occur.

PMID- 28740869
TI  - Comparing sequencing assays and human-machine analyses in actionable genomics for
      glioblastoma.
AB  - OBJECTIVE: To analyze a glioblastoma tumor specimen with 3 different platforms
      and compare potentially actionable calls from each. METHODS: Tumor DNA was
      analyzed by a commercial targeted panel. In addition, tumor-normal DNA was
      analyzed by whole-genome sequencing (WGS) and tumor RNA was analyzed by RNA
      sequencing (RNA-seq). The WGS and RNA-seq data were analyzed by a team of
      bioinformaticians and cancer oncologists, and separately by IBM Watson Genomic
      Analytics (WGA), an automated system for prioritizing somatic variants and
      identifying drugs. RESULTS: More variants were identified by WGS/RNA analysis
      than by targeted panels. WGA completed a comparable analysis in a fraction of the
      time required by the human analysts. CONCLUSIONS: The development of an effective
      human-machine interface in the analysis of deep cancer genomic datasets may
      provide potentially clinically actionable calls for individual patients in a more
      timely and efficient manner than currently possible. CLINICALTRIALSGOV
      IDENTIFIER: NCT02725684.

PMID- 28740870
TI  - Reduced Ventral Tegmental Area-Hippocampal Connectivity in Children and
      Adolescents Exposed to Early Threat.
AB  - BACKGROUND: Preclinical data suggest that early life stress has detrimental
      effects on the brain's dopaminergic system, particularly the mesocorticolimbic
      pathway. Altered dopamine function is thought to contribute to the development of
      stress-related pathologies; yet, little is known about the impact of early stress
      on dopamine systems during childhood and adolescence, when stress-related
      disorders frequently emerge. Here, we evaluate the impact of early threat
      exposure (violence, abuse) on functional connectivity of putative dopaminergic
      midbrain regions, the ventral tegmental area (VTA) and substantia nigra (SN),
      giving rise to mesocorticolimbic and nigrostriatal pathways, respectively.
      METHODS: Resting-state functional magnetic resonance imaging scans were completed
      in 43 trauma-exposed and 43 matched comparison youth (ages 7-17). Functional
      connectivity of the VTA and SN were compared between groups. RESULTS: The trauma
      group demonstrated lower functional connectivity between the VTA and hippocampus.
      No group differences in SN connectivity were observed. Across all participants,
      there were age-related decreases in connectivity of both VTA and SN with the
      hippocampus, suggesting that age-related attenuations in VTA-hippocampal
      circuitry may be exacerbated in trauma-exposed youth. Higher levels of anxiety
      symptomology were associated with reduced SN-nucleus accumbens connectivity.
      CONCLUSIONS: Prior research suggests that VTA-hippocampal circuitry is critical
      for the gating of new information into long-term memory. Lower connectivity in
      this circuitry suggests a novel mechanism that may serve to adaptively prevent
      the overwriting of a previously stored trauma memory, but at the same time
      contribute to the broad range of cognitive and emotional difficulties linked to
      early stress exposure.

PMID- 28740871
TI  - Severe radiation-induced leukoencephalopathy: Case report and literature review.

PMID- 28740872
TI  - Intravenous contrast-enhanced cone beam computed tomography (IVCBCT) of
      intrahepatic tumors and vessels.
AB  - PURPOSE: Liver tumors are challenging to visualize on cone beam computed
      tomography (CBCT) without intravenous (IV) contrast. Image guidance for liver
      cancer stereotactic body ablative radiation therapy (SABR) could be improved with
      the direct visualization of hepatic tumors and vasculature. This study
      investigated the feasibility of the use of IV contrast-enhanced CBCT (IV-CBCT) as
      a means to improve liver target visualization. METHODS AND MATERIALS: Patients on
      a liver SABR protocol underwent IV-CBCT before 1 or more treatment fractions in
      addition to a noncontrast CBCT. Image acquisition was initiated 0 to 30 seconds
      following injection and acquired over 60 to 120 seconds. "Stop and go" exhale
      breath-hold CBCT scans were used whenever feasible. Changes in mean CT number in
      regions of interest within visible vasculature, tumor, and adjacent liver were
      quantified between CBCT and IV-CBCT. RESULTS: Twelve pairs of contrast and
      noncontrast CBCTs were obtained in 7 patients. Intravenous-CBCT improved hepatic
      tumor visibility in breath-hold scans only for 3 patients (2 metastases, 1
      hepatocellular carcinoma). Visible tumors ranged in volume from 124 to 564 mL.
      Small tumors in free-breathing patients did not show enhancement on IVCBT.
      CONCLUSIONS: Intravenous-CBCT may enhance the visibility of hepatic vessels and
      tumor in CBCT scans obtained during breath hold. Optimization of IV contrast
      timing and reduction of artifacts to improve tumor visualization warrant further
      investigation.

PMID- 28740873
TI  - A phase 2 study of radiosurgery and temozolomide for patients with 1 to 4 brain
      metastases.
AB  - PURPOSE: To determine if temozolomide reduces the risk of distant brain failure
      (DBF, metachronous brain metastases) in patients with 1 to 4 brain metastases
      treated with radiosurgery without whole-brain radiation therapy (WBRT). METHODS
      AND MATERIALS: Twenty-five patients with newly diagnosed brain metastases were
      enrolled in a single institution phase 2 trial of radiosurgery (15-24 Gy) and
      adjuvant temozolomide. Temozolomide was continued for a total of 12 cycles unless
      the patient developed DBF, unacceptable toxicity, or systemic progression
      requiring other therapy. RESULTS: Twenty-five patients were enrolled between 2002
      and 2005; 3 were not evaluable for determining DBF. Of the remaining 22 patients,
      tumor types included non-small cell lung cancer (n = 8), melanoma (n = 7), and
      other (n = 7). Extracranial disease was present in 10 (45%) patients. The median
      number of tumors at the time of radiosurgery was 3 (range, 1-6). The median
      overall survival was 31 weeks. The median radiographic follow-up for patients who
      did not develop DBF was 33 weeks. Six patients developed DBF. The 1-year
      actuarial risk of DBF was 37%. CONCLUSIONS: In this study, there was a relatively
      low risk of distant brain failure observed in the nonmelanoma subgroup receiving
      temozolamide. However, patient selection factors rather than chemotherapy
      treatment efficacy are more likely the reason for the relatively low risk of
      distant brain failure observed in this study. Future trial design should account
      for these risk factors.

PMID- 28740874
TI  - An analysis of prognostic factors associated with recurrence in the treatment of
      atypical meningiomas.
AB  - BACKGROUND: There has been increased reporting of atypical meningioma (grade II)
      since the World Health Organization reclassification in 2000, and the use of
      postoperative radiation therapy (RT) in the treatment of these tumors is
      controversial. We evaluated patients treated at our institution to identify
      patient subgroups with increased risk of recurrence that may benefit from
      adjuvant RT. METHODS AND MATERIALS: We retrospectively assessed 50 patients
      treated for World Health Organization grade II meningiomas between March 2000 and
      February 2013. Sex, race, age of diagnosis, tumor location, performance status,
      size of tumor, MIB-1 index, resection status, and RT were recorded. Patient
      follow-up, recurrence, and vital status were measured to assess 3-year overall
      survival (OS) and recurrence free survival (RFS). RESULTS: The median follow-up
      was 37 months (range, 1-148). Female sex was associated with decreased RFS
      compared with male sex (86.1% vs 100%, P = .047). Subtotal resection demonstrated
      both inferior RFS (67.5% vs 96.6%, P = .025) and OS compared with gross total
      resection (70.0% vs 100%, P < .001). Tumors >4.5 cm had worse RFS than tumors
      <=4.5 cm (85.4% vs 100%, P = .025). Patient OS was lower in tumors with an MIB-1
      index >5% than <=5% (89.7% vs 100%, P = .008). Eastern Cooperative Oncology Group
      2-4 negatively impacted OS relative to patients with an Eastern Cooperative
      Oncology Group 0-1 (66.7% vs 100%, P < .001). CONCLUSIONS: Significantly higher
      rates of recurrence occurred in female sex, subtotal resection, and tumors larger
      than 4.5 cm. Further studies are needed to confirm these findings and determine
      whether patients without any of these risk factors can undergo surgical resection
      without adjuvant radiation therapy.

PMID- 28740875
TI  - Efficacy and toxicity of rectal cancer reirradiation using IMRT for patients who
      have received prior pelvic radiation therapy.
AB  - PURPOSE: Locally recurrent rectal cancer may cause significant morbidity. Prior
      reports of rectal cancer reirradiation following local recurrence suggest
      treatment efficacy, with variable rates of late toxicity. Modern techniques
      including intensity modulated radiation therapy (IMRT) may improve the
      therapeutic index. We report outcomes for pelvic reirradiation as treatment for
      rectal cancer using IMRT. METHODS AND MATERIALS: The records of 31 patients
      undergoing reirradiation for rectal cancer between 2004 and 2013 were reviewed.
      All patients underwent IMRT using an accelerated hyperfractionation (39 Gy in 1.5
      Gy fractions delivered twice daily, n=15) or once-daily fractionation technique
      (median dose, 30.4 Gy; range, 27-40 Gy in 15-22 fractions; n = 16). The median
      cumulative dose was 77 Gy (range, 59-113), and the median interval from prior
      pelvic radiation therapy was 39.8 months (range, 10.1-307.6). Treatment intent
      was palliative in 20 patients and neoadjuvant or adjuvant in 11 patients. Surgery
      was generally reserved for patients with an isolated local recurrence. Concurrent
      chemotherapy was administered for 25/31 patients, most frequently capecitabine
      (n=11) or continuous infusion 5-fluorouracil (n=10). RESULTS: Median follow-up
      was 11.3 months. The prescribed treatment was completed in 29/31 patients
      (93.5%). Among 18 patients with symptoms attributable to recurrent disease,
      successful palliation was achieved in 10/18 (55.6%). The rate of grade 2 and
      grade 3 acute toxicities was 32.3% and 3.2%, respectively. Local control rates at
      1 and 2 years were 61.3% and 47.3%, respectively. Median overall survival was
      21.9 months, and 1-year survival was 66.7% for patients who had surgical
      resection versus 58.7% for those who did not (P = .0802). CONCLUSIONS: Rectal
      cancer reirradiation using IMRT is well-tolerated in the setting of prior pelvic
      radiation therapy. Given significant risk of local progression, further dose
      escalation may be warranted for patients with life expectancy exceeding 1 year.

PMID- 28740876
TI  - Clinical application of lying-on-the-floor total skin electron irradiation for
      frail patients with cutaneous lymphoma: An emphasis on the importance of in vivo
      dosimetry.

PMID- 28740878
TI  - Use of mobile device technology to continuously collect patient-reported symptoms
      during radiation therapy for head and neck cancer: A prospective feasibility
      study.
AB  - PURPOSE: Accurate assessment of toxicity allows for timely delivery of supportive
      measures during radiation therapy for head and neck cancer. The current paradigm
      requires weekly evaluation of patients by a provider. The purpose of this study
      is to evaluate the feasibility of monitoring patient reported symptoms via mobile
      devices. METHODS AND MATERIALS: We developed a mobile application for patients to
      report symptoms in 5 domains using validated questions. Patients were asked to
      report symptoms using a mobile device once daily during treatment or more often
      as needed. Clinicians reviewed patient-reported symptoms during weekly symptom
      management visits and patients completed surveys regarding perceptions of the
      utility of the mobile application. The primary outcome measure was patient
      compliance with mobile device reporting. Compliance is defined as number of days
      with a symptom report divided by number of days on study. RESULTS: There were 921
      symptom reports collected from 22 patients during treatment. Median reporting
      compliance was 71% (interquartile range, 45%-80%). Median number of reports
      submitted per patient was 34 (interquartile range, 21-53). Median number of
      reports submitted by patients per week was similar throughout radiation therapy
      and there was significant reporting during nonclinic hours. Patients reported
      high satisfaction with the use of mobile devices to report symptoms. CONCLUSIONS:
      A substantial percentage of patients used mobile devices to continuously report
      symptoms throughout a course of radiation therapy for head and neck cancer.
      Future studies should evaluate the impact of mobile device symptom reporting on
      improving patient outcomes.

PMID- 28740877
TI  - Detection of late radiation damage on left atrial fibrosis using cardiac late
      gadolinium enhancement magnetic resonance imaging.
AB  - PURPOSE: This is a proof-of-principle study investigating the feasibility of
      using late gadolinium enhancement magnetic resonance imaging (LGE-MRI) to detect
      left atrium (LA) radiation damage. METHODS AND MATERIALS: LGE-MRI data were
      acquired for 7 patients with previous external beam radiation therapy (EBRT)
      histories. The enhancement in LA scar was delineated and fused to the computed
      tomography images used in dose calculation for radiation therapy. Dosimetric and
      normal tissue complication probability analyses were performed to investigate the
      relationship between LA scar enhancement and radiation doses. RESULTS: The
      average LA scar volume for the subjects was 2.5 cm3 (range, 1.2-4.1 cm3; median,
      2.6 cm3). The overall average of the mean dose to the LA scar was 25.9 Gy (range,
      5.8-49.2 Gy). Linear relationships were found between the amount of radiation
      dose (mean dose) (R2 = 0.8514, P = .03) to the LA scar-enhanced volume. The ratio
      of the cardiac tissue change (LA scar/LA wall) also demonstrated a linear
      relationship with the level of radiation received by the cardiac tissue (R2 =
      0.9787, P < .01). Last, the normal tissue complication probability analysis
      suggested a dose response function to the LA scar enhancement. CONCLUSIONS: With
      LGE-MRI and 3-dimensional dose mapping on the treatment planning system, it is
      possible to define subclinical cardiac damage and distinguish intrinsic cardiac
      tissue change from radiation induced cardiac tissue damage. Imaging myocardial
      injury secondary to EBRT using MRI may be a useful modality to follow cardiac
      toxicity from EBRT and help identify individuals who are more susceptible to EBRT
      damage. LGE-MRI may provide essential information to identify early screening
      strategy for affected cancer survivors after EBRT treatment.

PMID- 28740879
TI  - First case of Merkel cell carcinoma in a young patient with Sweet syndrome.

PMID- 28740880
TI  - Case report of tracheobronchial squamous cell carcinoma treated with radiation
      therapy and concurrent chemotherapy.

PMID- 28740881
TI  - Manufacture and evaluation of 3-dimensional printed sizing tools for use during
      intraoperative breast brachytherapy.
AB  - Three-dimensional (3D) printing has emerged as a promising modality for the
      production of medical devices. Here we describe the design, production, and
      implementation of a series of sizing tools for use in an intraoperative breast
      brachytherapy program. These devices were produced using a commercially available
      low-cost 3D printer and software, and their implementation resulted in an
      immediate decrease in consumable costs without affecting the quality of care or
      the speed of delivery. This work illustrates the potential of 3D printing to
      revolutionize the field of medical devices, enabling physicians to rapidly
      develop and prototype novel tools.

PMID- 28740882
TI  - Reexpansion of atelectasis caused by use of continuous positive airway pressure
      (CPAP) before radiation therapy (RT).
AB  - INTRODUCTION: Although radiation therapy (RT) is an effective treatment for
      malignant atelectasis, its accurate delivery is challenging because of difficulty
      differentiating between tumor and atelectatic lung. Furthermore, reexpansion of
      lung during treatment repositions tumor and normal structures necessitating
      replanning to ensure treatment accuracy. Facilitating lung reexpansion before
      initiation of RT may improve RT treatment accuracy, spare normal tissue, and
      reduce obstructive symptoms. We report a case of reexpansion of right upper lobe
      (RUL) atelectasis caused by use of continuous positive airway pressure (CPAP)
      before RT. CASE REPORT: A 52-year-old woman presented with dyspnea and cough.
      Imaging studies showed an RUL mass with atelectasis. Bronchoscopy showed
      extrinsic compression of the RUL and middle lobe bronchi. Biopsy showed small
      cell lung cancer. Staging with positron emission tomography-computed tomography
      (CT) and contrast enhanced CT of brain showed no other disease. Following 4
      cycles of platinum-based chemotherapy, CT imaging showed a decrease in tumor
      volume, but persistent RUL atelectasis. She agreed to participate in an
      institutional study to evaluate the use of CPAP to reduce respiratory motion and
      immobilize tumors during RT. During CPAP training, she complained of vertigo,
      headache, and weakness and refused simulation. The next day she reported less
      dyspnea and completed training and CT simulation without difficulty. CT
      simulation with CPAP showed reexpansion of the RUL. Lung volume increased from
      2170 to 3767 mL (74 %). Gross tumor volume, clinical volume, and planning volume
      decreased 46%, 45%, and 38%, respectively. Mean lung dose and mean heart dose
      decreased 20% and 51%, respectively. CPAP was used daily for 1 hour before and
      during treatment. Cone beam CT scans showed that the RUL remained inflated
      throughout treatment. CONCLUSION: This is the first reported use of CPAP for
      reexpansion of atelectasis before RT planning and treatment. Reexpansion of
      atelectasis improved RT planning, decreased dose to uninvolved lung, and removed
      the need for replanning. Further study of CPAP as an initial intervention to
      improve RT delivery in patients with malignant atelectasis is warranted.

PMID- 28740883
TI  - Feasibility and safety of cavity-directed stereotactic radiosurgery for brain
      metastases at a high-volume medical center.
AB  - OBJECTIVE: Our objective was to report safety and efficacy of stereotactic
      radiosurgery (SRS) to the surgical bed following resection of brain metastases.
      METHODS: Eighty-seven consecutive patients who underwent cavity-directed SRS to
      the operative bed for the treatment of brain metastases between 2002 and 2010
      were evaluated. SRS required a gadolinium-enhanced, high-resolution, T1-weighted
      magnetic resonance imaging for tumor targeting and delivered a median dose of 18
      Gy (14-22 Gy) prescribed to encompass the entire resection cavity. Whole brain
      irradiation was reserved for salvage. Patients were followed every 3 months with
      clinical examination and magnetic resonance imaging. Overall survival, local and
      regional recurrence, and factors affecting these outcomes were evaluated using
      Kaplan-Meier and log-rank analyses. RESULTS: The median imaging follow-up was 7.1
      months, with >40% of patients having imaging for >=1 year. Local control at 1 and
      2 years was 82% and 75%, respectively. Cavity recurrence was more common with a
      tumor diameter >3 cm (P < .020) or resection cavity volume >14 mL (P < .050). One
      year local control for tumors <2 cm, 2 cm to 3 cm, and >3 cm were 100%, 86%, and
      72%, respectively. Neither subtotal resection nor target margins >2 mm to 3 mm
      affected local control. The median overall survival was 14.3 months with
      actuarial 5-year survival of 20%. Actuarial regional central nervous system
      recurrence was 44% at 1 year. On univariate analysis, only the presence of
      extracranial disease was associated with survival (P < .001) and central nervous
      system failure (P < .030). CONCLUSIONS: Excellent local control is achievable
      with cavity-directed SRS in well-selected patients, particularly for lesions with
      diameter <3 cm and resection cavity volumes <14 mL. Long-term survival is
      possible for select patients.

PMID- 28740884
TI  - Neutron radiation therapy for advanced thyroid cancers.
AB  - PURPOSE: The aim of this study was to review institutional outcomes for advanced
      thyroid cancers treated with fast neutron radiation therapy (FNRT) and photon
      radiation therapy (RT). METHODS AND MATERIALS: In all, 62 consecutive patients
      were analyzed. Fifty-nine had stage IV disease. Twenty-three were treated with
      FNRT and 39 with photon RT. Median follow-up was 14 months. The primary endpoint
      was overall survival (OS). RESULTS: There was no significant difference in median
      OS between FNRT and photon RT (26 vs 16 months; P = .49). Patients with well
      differentiated histologies had superior median OS with photon RT (17 vs 69
      months; P = .04). There was a nonsignificant trend toward improved OS with FNRT
      for medullary and anaplastic histologies. CONCLUSIONS: Outcomes in this study are
      in line with historical results. There is an apparent detriment in OS with FNRT
      for well-differentiated histologies and a trend toward improved OS with medullary
      and anaplastic histologies that warrants further investigation.

PMID- 28740885
TI  - Grade 3 radiation dermatitis in a patient with presumed latent actinic lichen
      planus.

PMID- 28740886
TI  - Radiation-induced erectile dysfunction: Recent advances and future directions.
AB  - Prostate cancer is one of the most prevalent cancers and the second leading cause
      of cancer-related deaths in men in the United States. A large number of patients
      undergo radiation therapy (RT) as a standard care of treatment; however, RT
      causes erectile dysfunction (radiation-induced erectile dysfunction; RiED)
      because of late side effects after RT that significantly affects quality of life
      of prostate cancer patients. Within 5 years of RT, approximately 50% of patients
      could develop RiED. Based on the past and current research findings and number of
      publications from our group, the precise mechanism of RiED is under exploration
      in detail. Recent investigations have shown prostate RT induces significant
      morphologic arterial damage with aberrant alterations in internal pudendal
      arterial tone. Prostatic RT also reduces motor function in the cavernous nerve
      which may attribute to axonal degeneration may contributing to RiED. Furthermore,
      the advances in radiogenomics such as radiation induced somatic mutation
      identification, copy number variation and genome-wide association studies has
      significantly facilitated identification of biomarkers that could be used to
      monitoring radiation-induced late toxicity and damage to the nerves; thus,
      genomic- and proteomic-based biomarkers could greatly improve treatment and
      minimize arterial tissue and nerve damage. Further, advanced technologies such as
      proton beam therapy that precisely target tumor and significantly reduce off
      target damage to vital organs and healthy tissues. In this review, we summarize
      recent advances in RiED research and novel treatment modalities for RiED. We also
      discuss the possible molecular mechanism involved in the development of RiED in
      prostate cancer patients. Further, we discuss various readily available methods
      as well as novel strategies such as stem cell therapies, shockwave therapy, nerve
      grafting with tissue engineering, and nutritional supplementations might be used
      to mitigate or cure sexual dysfunction following radiation treatment.

PMID- 28740887
TI  - FGF18 signaling in the hair cycle resting phase determines radioresistance of
      hair follicles by arresting hair cycling.
AB  - PURPOSE: Telogen (resting phase) hair follicles (HFs) are more radioresistant
      than their anagen (growth phase) counterparts. Fibroblast growth factor (FGF) 18
      is strongly expressed in telogen HFs to maintain the telogen phase, whereas
      several other FGFs exert radioprotective effects; however, the role of FGF18 in
      the radioresistance of HFs remains unknown. This study focused on clarifying the
      role of FGF18 in the radioresistance of telogen HFs and its potential as a
      radioprotector. METHODS AND MATERIALS: BALB/c mice with telogen or plucking
      induced anagen HFs were exposed to total body irradiation with gamma-rays at 4 to
      12 Gy after intraperitoneal treatment with FGF18 or an FGF receptor inhibitor. A
      time course analysis was performed histologically and hair growth was observed 14
      or 15 days after depilation. Skin specimens were analyzed by DNA microarrays and
      Western blotting. RESULTS: Telogen irradiation at 6 Gy resulted in transient cell
      growth arrest, leading to successful hair growth, whereas anagen irradiation
      failed to promote hair growth. Telogen irradiation did not induce apoptosis in
      HFs or reduce HF stem cells, whereas anagen irradiation induced apoptosis and
      reduced stem cell numbers. The Inhibition of FGF receptor signaling during the
      telogen phase promoted HF cell proliferation; however, hair failed to grow after
      irradiation. In contrast, recombinant FGF18 induced transient cell growth arrest
      after anagen irradiation with enhanced DNA repair, leading to the inhibition of
      apoptosis, maintenance of HF stem cells, and successful hair growth. Moreover,
      FGF18 reduced the expression levels of genes promoting G2/M transition as well as
      the protein expression levels of cyclin B1 and cdc2 in skin, and induced G2/M
      arrest in the keratinocyte cell line HaCaT. CONCLUSIONS: These results suggest
      that FGF18 signaling mediates radioresistance in telogen HFs by arresting the
      cell cycle, and that FGF18 has potential as a radioprotector for radiation
      induced alopecia.

PMID- 28740888
TI  - Feasibility of 4D perfusion CT imaging for the assessment of liver treatment
      response following SBRT and sorafenib.
AB  - OBJECTIVES: To evaluate the feasibility of 4-dimensional perfusion computed
      tomography (CT) as an imaging biomarker for patients with hepatocellular
      carcinoma and metastatic liver disease. METHODS AND MATERIALS: Patients underwent
      volumetric dynamic contrast-enhanced CT on a 320-slice scanner before and during
      stereotactic body radiation therapy and sorafenib, and at 1 and 3 months after
      treatment. Quiet free breathing was used in the CT acquisition and multiple
      techniques (rigid or deformable registration as well as outlier removal) were
      applied to account for residual liver motion. Kinetic modeling was performed on a
      voxel-by-voxel basis in the gross tumor volume and normal liver resulting in 3
      dimensional parameter maps of blood perfusion, capillary permeability, blood
      volume, and mean transit time. Perfusion characteristics in the tumor and
      adjacent liver were correlated with radiation dose distributions to evaluate dose
      response. Paired t tests assessed change in spatial and histogram parameters from
      baseline to different time points during and after treatment. Technique
      reproducibility as well as the impact of arterial and portal vein input functions
      was also investigated using intra- and inter-subject variance and Bland-Altman
      analysis. RESULTS: Quantitative perfusion parameters were reproducible (+/-5.7%;
      range, 2%-10%) depending on tumor/normal liver type and kinetic parameter.
      Statistically significant reductions in tumor perfusion were measurable over the
      course of treatment and as early as 1 week after sorafenib administration (P <
      .05). Marked liver parenchyma perfusion reduction was seen with a strong dose
      response effect (R2 = 0.95) that increased significantly over the course
      treatment. CONCLUSIONS: The proposed methodology demonstrated feasibility of
      evaluating spatiotemporal changes in liver tumor perfusion and normal liver
      function following antiangiogenic therapy and radiation treatment warranting
      further evaluation of biomarker prognostication.

PMID- 28740889
TI  - Oncoplastic breast surgery in the setting of breast-conserving therapy: A
      systematic review.
AB  - Breast-conserving therapy (BCT), or breast-conserving surgery with adjuvant
      radiation therapy, has become a standard treatment alternative to mastectomy for
      women with early-stage breast cancer after many long-term studies have reported
      comparable rates of overall survival and local control. Oncoplastic breast
      surgery in the setting of BCT consists of various techniques that allow for an
      excision with a wider margin and a simultaneous enhancement of cosmetic sequelae,
      making it an ideal breast cancer surgery. Because of the parenchymal
      rearrangement that is routinely involved in oncoplastic techniques, however, the
      targeted tissue can be relocated, thus posing a challenge to localize the tumor
      bed for radiation planning. The goals of this systematic review are to address
      the challenges, outcomes, and cosmesis of oncoplastic breast surgery in the
      setting of BCT.

PMID- 28740890
TI  - Satisfaction of breast cancer patients regarding surgery and radiation therapy: A
      survey in Japan.
AB  - PURPOSE: To evaluate patient satisfaction in Japan and factors, including timing
      factors, cost, and specific medical practices derived from Western influence
      (shared decision-making and second opinion), which might affect satisfaction.
      METHODS AND MATERIALS: All patients who presented to 1 large Japanese department
      of radiation oncology for postoperative radiation therapy for breast cancer from
      September 2010 to November 2013 were included in this study. The questionnaire
      was distributed to patients after the radiation oncologist consultation, and
      patients were asked to complete it anonymously by the end of treatment. We
      measured patient satisfaction with overall treatment and for each treatment
      separately (surgery, radiation oncology). We further inquired regarding facts
      that could affect satisfaction, including time from diagnosis to treatment start,
      waiting time in waiting room for consultation, average length of consultations,
      out-of-pocket cost for breast cancer treatment, patients' opinion of the cost,
      level of inclusion of the patient in decision-making, level of the patient
      sharing her feelings with her physician, and whether the patients had asked for
      second opinion. RESULTS: Of 364 patients surveyed, 214 (58.5%) responded. Overall
      satisfaction and satisfaction with surgeon and with radiation oncologist were
      95.7%, 98.5%, and 98.2%, respectively. Factors correlated with satisfaction were
      waiting time for the consult in the waiting room, treatment cost, and perceived
      degree of sharing feelings with physicians. Overall, 27 patients (12.6%) reported
      having asked for second opinions. Of those who did not seek a second opinion,
      most (173) indicated that they did not think it was necessary. CONCLUSIONS: In a
      large, typical Japanese radiation oncology practice, breast cancer patients'
      satisfaction correlated with waiting time, cost, and the rate with which the
      patient shared her feelings with her physician. This illuminates targets for
      quality improvement within the Japanese system and provides interesting cross
      cultural comparative data for other countries in which the context of care may
      differ.

PMID- 28740891
TI  - Esophageal motion characteristics in thoracic esophageal cancer: Impact of
      clinical stage T4 versus stages T1-T3.
AB  - PURPOSE: The main purpose was to investigate the differences of the esophageal
      motion (EM) and the internal target volume (ITV) margins for the esophagus
      between clinical T1-T3 (cT1-T3) and cT4 cases, using 4-dimensional computed
      tomography. A secondary purpose was to assess the metastatic lymph nodal motion
      (NM) and the ITV margins for lymph nodes (LNs) using the datasets of patients
      with nodal involvement pathologically defined. METHODS AND MATERIALS: We analyzed
      patients with thoracic esophageal cancer consecutively treated with definitive
      chemoradiation, measuring the EM and the ITV margins in the left-right,
      anteroposterior, and superoinferior directions. All esophageal contours were
      divided at the carina. The EM and NM were measured from the displacement of the
      centroid point between 0% images (at the end of inhalation) and 50% images (at
      the end of exhalation). The ITV margins were defined as the maximum distance in
      each direction from the clinical target volume at the 4-dimensional computed
      tomography average images to the intersection of the clinical target volume at
      the 0% and 50% images of complete coverage in each patient. RESULTS: The EM below
      the carina in cT4 was significantly smaller than that in cT1-T2 in all directions
      (P < .01) and than that in cT3 in all directions (left-right: P = .03,
      anteroposterior and superoinferior: P < .01). The EM in the case of a cT4 tumor
      located below the carina was smaller than that in the case of cT4 tumor located
      above the carina. The NM of abdominal-LNs was much larger than that of
      cervicothoracic-LNs and the EM below the carina. These tendencies were similar in
      the ITV measurements. CONCLUSIONS: The EM and the ITV margins in cT4 were
      significantly smaller than those in cT1-T3. The NM and the ITV margins of
      abdominal LNs were much larger than those of cervicothoracic LNs and the
      esophagus. In clinical radiation therapy planning for esophageal cancer, we
      should take cT stage into consideration.

PMID- 28740892
TI  - Chemoradiation therapy with docetaxel in elderly patients with stage II/III
      esophageal cancer: A phase 2 trial.
AB  - PURPOSE: The most effective treatments in elderly patients with esophageal cancer
      remain a subject of debate. This multicenter phase 2 study was designed to
      evaluate the efficacy and toxicity of chemoradiation therapy (CRT) with docetaxel
      (DTX) in elderly patients with stage II/III (non-T4) esophageal cancer. METHODS
      AND MATERIALS: Patients >=70 years of age with clinical stage II/III esophageal
      cancer received DTX at a weekly dose of 10 mg/m2 during 6 consecutive weeks and
      concurrent radiation therapy (60 Gy in 30 fractions). The primary endpoint was
      the 2-year survival rate, and the required number of enrolled patients was 37.
      RESULTS: Between July 2008 and January 2011, 16 patients were enrolled. The study
      was prematurely closed because of slow accrual. Characteristics of the patients
      were as follows: median age, 77 years (range, 73-81); performance status 0/1,
      4/12; and clinical stage IIA/IIB/III, 3/4/9. Of the 16 patients, 14 (87.5%)
      completed the CRT. The 2-year survival rate was 62.5% (90% confidence interval
      [CI], 42.5-82.5). The median survival time was 27.7 months (95% CI, 23.3-32.2
      months) and the median progression-free survival was 15.2 months (95% CI, 5.4
      25.0 months). Seven patients achieved complete response, resulting in a complete
      response rate of 43.8% (95% CI, 19.8-70.1). Grade 3 or higher acute toxicities
      included esophagitis (31.3%), anorexia (12.5%), leukopenia (6.3%), neutropenia
      (6.3%), thrombocytopenia (6.3%), mucositis (6.3%), and infection (6.3%). Grade 3
      or higher late toxicities included esophagitis (12.5%), pleural effusion (12.5%),
      pneumonitis (6.3%), and pericardial effusion (6.3%). CONCLUSIONS: CRT with DTX
      might be a treatment option for elderly patients with stage II/III esophageal
      cancer, particularly for patients who are medically unfit for surgery or
      cisplatin-containing therapy. However, further improvements of this therapy are
      required to decrease the incidence of esophagitis.

PMID- 28740893
TI  - Stereotactic body radiotherapy (SBRT) for locally advanced extrahepatic and
      intrahepatic cholangiocarcinoma.
AB  - OBJECTIVES: We report single-institution clinical efficacy and safety outcomes
      for patients with unresectable locally advanced cholangiocarcinoma who were
      treated with stereotactic body radiation therapy (SBRT) and a subset of patients
      who received neoadjuvant SBRT and chemotherapy as part of an orthotopic liver
      transplantation (OLT) protocol. METHODS AND MATERIALS: From October 2008 to June
      2015, 31 consecutive patients with unresectable extrahepatic (n = 25) or
      intrahepatic (n = 6) cholangiocarcinoma were treated with SBRT and
      retrospectively analyzed. Four patients underwent liver transplantation, and 1
      underwent resection. SBRT was delivered in 5 fractions with a median dose of 40
      Gy. Toxicity was scored using the Common Terminology Criteria for Adverse Events
      Version 4.0. Overall survival (OS), time to progression, and local control were
      estimated using the Kaplan-Meier method. RESULTS: The median follow-up time was
      11.5 months. The 1- and 2-year OS rates were 59% and 33%, respectively, with a
      median survival of 15.7 months. The 1- and 2-year freedom from progression was
      67% and 34%, respectively. Median time to progression was 16.8 months. Nine
      patients had local failure. The actuarial 1- and 2-year local control rates were
      78% and 47%, respectively. Among patients who also had OLT, the median OS was
      31.3 months. Twenty-four patients (77%) experienced some form of acute grade 1-2
      toxicity, most commonly fatigue or pain. Five patients (16%) experienced grade
      >=3 toxicity. CONCLUSIONS: SBRT is a promising option for patients with
      unresectable or recurrent cholangiocarcinoma either as a component of neoadjuvant
      therapy prior to OLT or as part of definitive therapy for patients who are
      unresectable and not eligible for transplantation.

PMID- 28740894
TI  - Postoperative radiation therapy is associated with a reduced risk of local
      recurrence among low risk Merkel cell carcinomas of the head and neck.
AB  - PURPOSE: Merkel cell carcinoma (MCC) is a rare and often aggressive skin cancer.
      Typically, surgery is the primary treatment. Postoperative radiation therapy
      (PORT) is often recommended to improve local control. It is unclear whether PORT
      is indicated in patients with favorable Stage IA head and neck (HN) MCC. METHODS
      AND MATERIALS: We conducted a retrospective analysis of 46 low-risk HN MCC cases
      treated between 2006 and 2015. Inclusion criteria were defined as a primary tumor
      size of <= 2 cm, negative pathological margins, negative sentinel lymph node
      biopsy, and no immunosuppression. Local recurrence (LR) was defined as tumor
      recurrence within 2 cm of the primary surgical bed and estimated with the Kaplan
      Meier method. RESULTS: Omission of PORT was offered to all 46 patients, of which
      23 patients received PORT and 23 did not. No patient received adjuvant
      chemotherapy. There were no significant differences in surgical margins, tumor
      size, depth, lympho-vascular invasion status, or demographics between the two
      patient groups. Median follow-up for all patients was 3.7 years. Six of the 23
      patients who did not receive PORT developed an LR. Compared to the group that
      received PORT, there was a significantly higher risk of LR in the group treated
      without PORT (26% vs. 0%, P = .02). Median time to LR was 11 months. All local
      failures were effectively salvaged. There was no difference in MCC-specific and
      overall survival between the 2 groups. CONCLUSIONS: For patients with HN MCC,
      omission of PORT was associated with a significantly higher risk of local
      recurrence even among those patients with the lowest-risk tumors (i.e., Stage IA
      without immune suppression). Thus, it is important to weigh the benefits of PORT
      against the side effect profile on a case-specific basis for each patient.

PMID- 28740895
TI  - Using low-dose radiation to potentiate the effect of induction chemotherapy in
      head and neck cancer: Results of a prospective phase 2 trial.
AB  - PURPOSE: Low-dose fractionated radiation therapy (LDFRT) induces effective cell
      killing through hyperradiation sensitivity and potentiates effects of
      chemotherapy. We report our second investigation of LDFRT as a potentiator of the
      chemotherapeutic effect of induction carboplatin and paclitaxel in locally
      advanced squamous cell cancer of the head and neck (SCCHN). EXPERIMENTAL DESIGN:
      Two cycles of induction therapy were given every 21 days: paclitaxel (75 mg/m2)
      on days 1, 8, and 15; carboplatin (area under the curve 6) day 1; and LDFRT 50
      cGy fractions (2 each on days 1, 2, 8, and 15). Objectives included primary site
      complete response rate; secondary included overall survival, progression-free
      survival (PFS), disease-specific survival, and toxicity. RESULTS: A total of 24
      evaluable patients were enrolled. Primary sites included oropharynx (62.5%),
      larynx (20.8%), oral cavity (8.3%), and hypopharynx (8.3%). Grade 3/4 toxicities
      included neutropenia (20%), leukopenia (32%), dehydration/hypotension (8%),
      anemia (4%), infection (4%), pulmonary/allergic rhinitis (4%), and diarrhea (4%).
      Primary site response rate was 23/24 (95.8%): 15/24 (62.5%) complete response,
      8/24 (33.3%) partial response, and 1/24 (4.2%) stable disease. With median follow
      up of 7.75 years, 9-year rates for overall survival were 49.4% (95% confidence
      interval [CI], 30.5-79.9), PFS was 72.2% (CI, 55.3-94.3), and disease-specific
      survival was 65.4% (44.3-96.4). CONCLUSION: Chemopotentiating LDFRT combined with
      paclitaxel and carboplatin is effective in SCCHN and provided an excellent median
      overall survival of 107.2 months, with median PFS not yet reached in this locally
      advanced SCCHN cohort. This compares favorably to prior investigations and caused
      fewer grade 3 and 4 toxicities than more intensive, 3-drug induction regimens.
      This trial demonstrates the innovative use of LDFRT as a potentiator of
      chemotherapy.

PMID- 28740896
TI  - The big data effort in radiation oncology: Data mining or data farming?
AB  - Although large volumes of information are entered into our electronic health care
      records, radiation oncology information systems and treatment planning systems on
      a daily basis, the goal of extracting and using this big data has been slow to
      emerge. Development of strategies to meet this goal is aided by examining issues
      with a data farming instead of a data mining conceptualization. Using this model,
      a vision of key data elements, clinical process changes, technology issues and
      solutions, and role for professional societies is presented. With a better view
      of technology, process and standardization factors, definition and prioritization
      of efforts can be more effectively directed.

PMID- 28740897
TI  - Myeloablative conditioning with total body irradiation for AML: Balancing
      survival and pulmonary toxicity.
AB  - PURPOSE: The purpose of this study was to compare leukemia-free survival (LFS)
      and other clinical outcomes in patients with acute myelogenous leukemia who
      underwent a myeloablative allogeneic stem cell transplant with and without total
      body irradiation (TBI). METHODS AND MATERIALS: Adult patients with acute
      myelogenous leukemia undergoing myeloablative allogeneic stem cell transplant at
      Duke University Medical Center between 1995 and 2012 were included. The primary
      endpoint was LFS. Secondary outcomes included overall survival (OS), nonrelapse
      mortality, and the risk of pulmonary toxicity. Kaplan-Meier survival estimates
      and Cox proportional hazards multivariate analyses were performed. RESULTS: A
      total of 206 patients were evaluated: 90 received TBI-based conditioning regimens
      and 116 received chemotherapy alone. Median follow-up was 36 months. For all
      patients, 2-year LFS and OS were 36% (95% confidence interval [CI], 29-43) and
      39% (95% CI, 32-46), respectively. After adjusting for known prognostic factors
      using a multivariate analysis, TBI was associated with improved LFS (hazard
      ratio: 0.63; 95% CI: 0.44-0.91) and OS (hazard ratio: 0.63; 95% CI, 0.43-0.91).
      There was no difference in nonrelapse mortality between cohorts, but pulmonary
      toxicity was significantly more common with TBI (2-year incidence 42% vs 12%, P <
      .001). High-grade pulmonary toxicity predominated with both conditioning
      strategies (70% and 93% of cases were grade 3-5 with TBI and chemotherapy alone,
      respectively). CONCLUSIONS: TBI-based regimens were associated with superior LFS
      and OS but at the cost of increased pulmonary toxicity.

PMID- 28740898
TI  - Priority-driven plan optimization in locally advanced lung patients based on
      perfusion SPECT imaging.
AB  - PURPOSE: Limits on mean lung dose (MLD) allow for individualization of radiation
      doses at safe levels for patients with lung tumors. However, MLD does not account
      for individual differences in the extent or spatial distribution of pulmonary
      dysfunction among patients, which leads to toxicity variability at the same MLD.
      We investigated dose rearrangement to minimize the radiation dose to the
      functional lung as assessed by perfusion single photon emission computed
      tomography (SPECT) and maximize the target coverage to maintain conventional
      normal tissue limits. METHODS AND MATERIALS: Retrospective plans were optimized
      for 15 patients with locally advanced non-small cell lung cancer who were
      enrolled in a prospective imaging trial. A staged, priority-based optimization
      system was used. The baseline priorities were to meet physical MLD and other dose
      constraints for organs at risk, and to maximize the target generalized equivalent
      uniform dose (gEUD). To determine the benefit of dose rearrangement with
      perfusion SPECT, plans were reoptimized to minimize the generalized equivalent
      uniform functional dose (gEUfD) to the lung as the subsequent priority. RESULTS:
      When only physical MLD is minimized, lung gEUfD was 12.6 +/- 4.9 Gy (6.3-21.7
      Gy). When the dose is rearranged to minimize gEUfD directly in the optimization
      objective function, 10 of 15 cases showed a decrease in lung gEUfD of >20% (lung
      gEUfD mean 9.9 +/- 4.3 Gy, range 2.1-16.2 Gy) while maintaining equivalent
      planning target volume coverage. Although all dose-limiting constraints remained
      unviolated, the dose rearrangement resulted in slight gEUD increases to the cord
      (5.4 +/- 3.9 Gy), esophagus (3.0 +/- 3.7 Gy), and heart (2.3 +/- 2.6 Gy).
      CONCLUSIONS: Priority-driven optimization in conjunction with perfusion SPECT
      permits image guided spatial dose redistribution within the lung and allows for a
      reduced dose to the functional lung without compromising target coverage or
      exceeding conventional limits for organs at risk.

PMID- 28740899
TI  - Cryptic Nocardia nova brain abscess postradiation treatment and neurosurgery in a
      patient with small cell lung cancer: A case report and review of the literature.

PMID- 28740900
TI  - Management approach for recurrent brain metastases following upfront radiosurgery
      may affect risk of subsequent radiation necrosis.
AB  - PURPOSE: Many patients treated with stereotactic radiosurgery (SRS) alone as
      initial treatment require 1 or more subsequent salvage therapies. This study
      aimed to determine if commonly used salvage strategies are associated with
      differing risks of radiation necrosis (RN). METHODS AND MATERIALS: All patients
      treated with upfront SRS alone for brain metastases at our institution were
      retrospectively analyzed. Salvage treatment details were obtained for brain
      failures. Patients who underwent repeat SRS to the same lesion were excluded. RN
      was determined based on pathological confirmation or advanced brain imaging
      consistent with RN in a symptomatic patient. Patients were grouped according to
      salvage treatment and rates of RN were compared via Fisher's exact tests.
      RESULTS: Of 284 patients treated with upfront SRS alone, 132 received salvage
      therapy and 44 received multiple salvage treatments. This included 31 repeat SRS
      alone, 58 whole brain radiation therapy (WBRT) alone, 28 SRS and WBRT, 7 surgery
      alone, and 8 surgery with adjuvant radiation. With a median follow-up of 10
      months, the rate of RN among all patients was 3.17% (9/284), salvaged patients
      4.55% (6/132), and never salvaged patients 1.97% (3/152). Receiving salvage
      therapy did not significantly increase RN risk (P = .31). Of the patients
      requiring salvage treatments, the highest RN rate was among patients that had
      both salvage SRS and WBRT (delivered as separate salvage therapies) (6/28,
      21.42%). RN rate in this group was significantly higher than in those treated
      with repeat SRS alone (0/31), WBRT alone (0/58), surgery alone (0/7), and surgery
      with adjuvant radiation (0/8). Comparing salvage WBRT doses <30 Gy versus >=30 Gy
      revealed no effect of dose on RN rate. Additionally, among patients who received
      multiple SRS treatments, number of treated lesions was not predictive of RN
      incidence. CONCLUSION: Our results suggest that initial management approach for
      recurrent brain metastasis after upfront SRS does not affect the rate of RN.
      However, the risk of RN significantly increases when patients are treated with
      both repeat SRS and salvage WBRT. Methods to improve prediction of toxicity and
      optimize patient selection for salvage treatments are needed.

PMID- 28740901
TI  - Long-term outcomes of dose-escalated intensity modulated radiation therapy alone
      without androgen deprivation therapy for patients with intermediate and high-risk
      prostate cancer.
AB  - OBJECTIVE: The addition of androgen deprivation therapy (ADT) to conventional
      radiation therapy improves overall survival (OS) in intermediate- and high-risk
      prostate cancer. The benefit of ADT to added to dose-escalated radiotherapy is
      less clear. The aim of this study was to report disease control outcomes and to
      identify prognostic variables associated with favorable outcomes in patients with
      intermediate- and high-risk prostate cancer treated with dose-escalated radiation
      therapy without ADT. METHODS AND MATERIALS: From September 2001 to March 2010,
      127 patients with intermediate- or high-risk prostate cancer were treated with
      dose-escalated radiation otherapy without ADT. Biochemical recurrence-free
      survival (bRFS), distant metastases-free survival (DMFS), prostate cancer
      specific mortality, and OS were assessed. Univariate and multivariate analyses
      using Cox regression modeling were performed. RESULTS: The median follow-up was
      6.5 years, and the 5-year estimated bRFS, DMFS, prostate cancer-specific
      mortality, and OS for all patients was 89%, 96.1%, 98.4%, and 96.9% respectively.
      On multivariate analysis, factors that predict bRFS include risk group and PSA
      nadir, and factors that predict DMFS include perineural invasion, risk group, and
      PSA nadir. CONCLUSIONS: Patients with favorable intermediate-risk cancer could
      likely be treated with dose-escalated radiation therapy without ADT. Patients
      with high-risk and unfavorable intermediate-risk cancer, perineural invasion, and
      PSA nadir >=1ng/dL had worse outcomes and likely need distinct therapeutic
      approaches.

PMID- 28740902
TI  - Urinary quality of life outcomes in men who were treated with image-guided
      intensity-modulated radiation therapy for prostate cancer.
AB  - PURPOSE: Quality of life (QoL) outcomes play a major role in the treatment
      selection for prostate cancer (CaP). We evaluated the urinary QoL outcomes in men
      who were treated with image-guided intensity-modulated radiation therapy (IG
      IMRT) for CaP. METHODS AND MATERIALS: We enrolled men who were diagnosed with CaP
      and underwent IG-IMRT in a large urological group practice into a prospectively
      maintained database. The typical radiation treatment dosage to prostates and
      seminal vesicles was 8100 cGy in 45 fractions. Urinary QoL was self-assessed
      using the standardized incontinence grade and International Prostate Symptom
      Score (IPSS) at baseline and at each follow-up visit. We evaluated the cumulative
      incidence of urinary incontinence and changes in both continence and IPSS over
      time. RESULTS: Of the 3602 men who were eligible for analysis, 3086 (85.7%) had
      no urinary incontinence; 479 (13.3 %) had minimal incontinence (no requirement
      for pads), and 37 (1.0 %) had significant urinary incontinence that required the
      use of pads or interfered with activities of daily living, at baseline. After a
      median follow-up of 24 months (range: 12.0-41.0 months), these numbers were
      80.6%, 17.4%, and 2.0%, respectively. Radiation therapy appeared to have a
      beneficial effect on some men: 54.1% of men with minimal incontinence became
      completely continent of urine during follow-up. Of those with significant urinary
      incontinence, 29.7% reported resolution and 27.0% reported improved symptoms with
      no requirement for pads. Of the 1276 men with moderate IPSS, the mean IPSS
      decreased from 12 to 9.8 at the time of the last follow-up (P < .001). Similarly,
      of the 233 men with severe IPSS, the mean IPSS decreased from 24 to 13 at the
      time of the last follow-up (P < .001). CONCLUSION: IG-IMRT for clinically
      localized CaP is associated with a relatively low incidence of urinary
      incontinence. Although unexplained, IG-IMRT seems to improve symptoms in some men
      with baseline urinary incontinence and moderate-to-severe IPSS.

PMID- 28740903
TI  - Hypofractionated image guided radiation therapy followed by prostate seed implant
      boost for men with newly diagnosed intermediate and high risk adenocarcinoma of
      the prostate: Preliminary results of a phase 2 prospective study.
AB  - PURPOSE: A phase 2 protocol was designed and implemented to assess the toxicity
      and efficacy of hypofractionated image guided intensity modulated radiation
      therapy (IG-IMRT) combined with low-dose rate 103Pd prostate seed implant for
      treatment of localized intermediate- and high-risk adenocarcinoma of the
      prostate. METHODS AND MATERIALS: This is a report of an interim analysis on 24
      patients enrolled on an institutional review board-approved phase 2 single
      institution study of patients with intermediate- and high-risk adenocarcinoma of
      the prostate. The median pretreatment prostate-specific antigen level was 8.15
      ng/mL. The median Gleason score was 4 + 3 = 7 (range, 3 + 4 = 7 - 4 + 4 = 8), and
      the median T stage was T2a. Of the 24 patients, 4 (17%) were high-risk patients
      as defined by the National Comprehensive Cancer Network criteria, version 2016.
      The treatment consisted of 2465 cGy in 493 cGy/fraction of IG-IMRT to the
      prostate and seminal vesicles. This was followed by a 103Pd transperineal
      prostate implant boost (prescribed dose to 90% of the prostate volume of 100 Gy)
      using intraoperative planning. Five patients received neoadjuvant, concurrent,
      and adjuvant androgen deprivation therapy. RESULTS: The median follow-up was 18
      months (range, 1-42 months). The median nadir prostate-specific antigen was 0.5
      ng/mL and time to nadir was 16 months. There was 1 biochemical failure associated
      with distant metastatic disease without local failure. Toxicity (acute or late)
      higher than grade 3 was not observed. There was a single instance of late grade 3
      genitourinary toxicity secondary to hematuria 2 years and 7 months after
      radiation treatment. There were no other grade 3 gastrointestinal or
      genitourinary toxicities. CONCLUSIONS: Early results on the toxicity and efficacy
      of the combination of hypofractionated IG-IMRT and low-dose-rate brachytherapy
      boost are favorable. Longer follow-up is needed to confirm safety and
      effectiveness.

PMID- 28740904
TI  - Disparities in staging prostate magnetic resonance imaging utilization for
      nonmetastatic prostate cancer patients undergoing definitive radiation therapy.
AB  - PURPOSE: There is growing evidence supporting incorporating multiparametric (mp)
      magnetic resonance imaging (MRI) scans into risk stratification, active
      surveillance, and treatment paradigms for prostate cancer. The purpose of our
      study was to determine whether demographic disparities exist in staging MRI
      utilization for prostate cancer patients. METHODS AND MATERIALS: An institutional
      database of 705 nonmetastatic prostate cancer patients treated with radiation
      therapy from 2005 through 2013 was used to identify patients undergoing versus
      not undergoing pretreatment diagnostic prostate mpMRI. Uni- and multivariable
      logistic regression evaluated the relationship of clinical and demographic
      characteristics with MRI utilization. RESULTS: All demographic variables
      assessed, except the other race category, were significantly associated with MRI
      utilization (all P < .05), including age (odds ratio [OR], 0.92), black race (OR,
      0.51), poverty (OR, 0.53), closer distance to radiation facility (OR, 1.79), and
      nonprivate primary insurance (OR, 0.57) on univariable analysis, while clinical
      stage T3 (OR, 3.37) was the only clinical characteristic. On multivariable
      analysis stratified by D'Amico risk group, age remained significant across all
      risk groups, whereas the black versus white racial (OR, 0.21; 95% confidence
      interval, 0.08-0.55) and nonprivate versus private insurance type (OR, 0.37; 95%
      confidence interval, 0.16-0.86) disparities persisted in the low-risk group.
      Clinical stage T3 remained associated in the high-risk group. For race
      specifically, the percentages of whites, blacks, and others undergoing MRI in the
      overall cohort and by risk group were, respectively: overall, 80% (343/427), 68%
      (156/231), and 85% (40/47); low risk, 86%, 56%, and 63%; intermediate risk, 79%,
      72%, and 95%; and high risk, 72%, 72%, and 100%. CONCLUSIONS: In this urban,
      academic center cohort, older patients across all risk groups and black or
      nonprivate insurance patients in the low risk group were less likely to undergo
      staging prostate MRI scans. Further research should investigate these differences
      to ensure equitable utilization across all demographic groups considering the
      burden of prostate cancer disparities.

PMID- 28740905
TI  - Use of acupuncture to alleviate side effects in radiation oncology: Current
      evidence and future directions.
AB  - Several reports have shown that acupuncture is an effective method of
      complementary medicine; however, only a few of these reports have focused on
      oncological patients treated with radiation therapy. Most of these studies
      discuss a benefit of acupuncture for side-effect reduction; however, not all
      could demonstrate significant improvements. Thus, innovative trial designs are
      necessary to confirm that acupuncture can alleviate side effects related to
      radiation therapy. In the present manuscript, we perform a broad review and
      discuss pitfalls and limitations of acupuncture in parallel with standard
      radiation therapy, which lead the way to novel treatment concepts.

PMID- 28740906
TI  - The development, commercialization, and clinical context of yttrium-90
      radiolabeled resin and glass microspheres.
AB  - Selective internal radiation therapy has emerged as a well-accepted therapeutic
      for primary and metastatic hepatic malignancies. This therapeutic modality
      requires the combined efforts of multiple medical disciplines to ensure the safe
      delivery of yttrium-90 (90Y)-labeled microspheres. The development of this
      therapy followed decades of clinical research involving tumor vascularity and
      microsphere development. Today, it is essential that treating physicians have a
      thorough understanding of hepatic tumor vascularity and 90Y microsphere
      characteristics before undertaking this complex intervention. This review
      explores the contributions of early investigators of this therapy, as well as the
      development, US Food and Drug Administration approval, manufacturing process, and
      attributes of the 2 commercially available 90Y radiolabeled microsphere device to
      clarify the key physical differences between the products.

PMID- 28740907
TI  - Functional imaging equivalence and proof of concept for image-guided adaptive
      radiotherapy with fixed gantry and rotating couch.
AB  - PURPOSE: The purpose of this article is to present the first imaging experiments
      to demonstrate the functional equivalence between a conventional rotational
      gantry and a fixed-beam imaging geometry, and the feasibility of an iterative
      image-reconstruction technique under gravitational deformation. METHODS AND
      MATERIALS: Experiments were performed using an Elekta Axesse with Agility MLC and
      XVI, a custom-built rotating phantom stage, a Catphan QA phantom, and a porcine
      heart. For the imaging equivalence, a conventional cone beam computed tomography
      (CBCT) of the Catphan was acquired, as well as a set of 660 x-ray projections
      with a static gantry and rotating Catphan. Both datasets were reconstructed with
      the Feldkamp-Davis-Kress (FDK) algorithm, and the resultant volumetric images
      were compared using standard metrics. For imaging under gravitational
      deformation, a conventional CBCT of the Catphan and a set of 660 x-ray
      projections with a static gantry and rotating Catphan were also acquired with a
      porcine heart. The conventional CBCT was reconstructed using FDK. The projections
      that were acquired with the heart rotating were sorted into angular bins and
      reconstructed with prior image constrained compressed sensing using a deformation
      blurred FDK prior. Deformation was quantified with B-spline transformation-based
      deformable image registration. RESULTS: For imaging equivalence, the difference
      between the two Catphan images was consistent with Poisson noise. For imaging
      under gravitational deformation, the conventional CBCT porcine heart image
      (ground truth at 0 degrees) matched the static gantry, rotating heart
      reconstruction with a mean magnitude of <3 mm and maximum magnitude of <5 mm of
      the deformation vector field. The mean deformation of the rotating heart was 3.0
      to 8.9 mm, up to 16.1 mm maximum deformation. Deformation was mainly observed in
      the direction of gravity. CONCLUSIONS: We have demonstrated imaging equivalence
      in cone beam CT reconstructions between rigid phantom images acquired with a
      conventional rotating gantry and with a fixed-gantry and rotating phantom. We
      have presented a method for image reconstruction under a fixed-beam imaging
      geometry using a deformable phantom.

PMID- 28740908
TI  - Preplanning prediction of the left anterior descending artery maximum dose based
      on patient, dosimetric, and treatment planning parameters.
AB  - PURPOSE: Maximum dose to the left anterior descending artery (LADmax) is an
      important physical constraint to reduce the risk of cardiovascular toxicity. We
      generated a simple algorithm to guide the positioning of the tangent fields to
      reliably maintain LADmax <10 Gy. METHODS AND MATERIALS: Dosimetric plans from 146
      consecutive women treated prone to the left breast enrolled in prospective
      protocols of accelerated whole breast radiation therapy, with a concomitant daily
      boost to the tumor bed (40.5 Gy/15 fraction to the whole breast and 48 Gy to the
      tumor bed), provided the training set for algorithm development. Scatter plots
      and correlation coefficients were used to describe the bivariate relationships
      between LADmax and several parameters: distance from the tumor cavity to the
      tangent field edge, cavity size, breast separation, field size, and distance from
      the tangent field. A logistic sigmoid curve was used to model the relationship of
      LADmax and the distance from the tangent field. Furthermore, we tested this
      prediction model on a validation data set of 53 consecutive similar patients.
      RESULTS: A lack of linear relationships between LADmax and distance from cavity
      to LAD (-0.47), cavity size (-0.18), breast separation (-0.02), or field size (
      0.28) was observed. In contrast, distance from the tangent field was highly
      negatively correlated to LADmax (-0.84) and was used in the models to predict
      LADmax. From a logistic sigmoid model we selected a cut-point of 2.46 mm (95%
      confidence interval, 2.19-2.74 mm) greater than which LADmax is <10 Gy (95%
      confidence interval, 9.30-10.72 Gy) and LADmean is <3.3 Gy. CONCLUSIONS: Placing
      the edge of the tangents at least 2.5 mm from the closest point of the contoured
      LAD is likely to assure LADmax is <10 Gy and LADmean is <3.3 Gy in patients
      treated with prone accelerated breast radiation therapy.

PMID- 28740909
TI  - Lessons learned from reirradiation of recurrent skull base meningioma: A case
      report and review of the literature.

PMID- 28740910
TI  - Dosimetric advantages of intensity modulated radiation therapy in locally
      advanced lung cancer.
AB  - PURPOSE: Radiation therapy plays an essential role in the treatment of locally
      advanced lung cancer, but it inevitably leads to incidental and unnecessary dose
      to critical organs, including the lung, heart, and esophagus. Numerous radiation
      dose-volumetric parameters have been associated with increased risk of morbidity
      and mortality. The purpose of the present study is to quantify differences in
      normal tissue radiation exposure with intensity modulated radiation therapy
      (IMRT) compared with 3-dimensional conformal radiation therapy (3D-CRT). METHODS
      AND MATERIALS: Twenty-four consecutive patients with locally advanced lung cancer
      undergoing definitive IMRT were enrolled on a phase 1 protocol. For each patient,
      an optimized 3D-CRT plan was also designed. Plans were normalized in terms of
      planning target coverage with a standard dose of 60 Gy in 2-Gy fractions with a
      subset of patients also receiving elective nodal irradiation to a dose of 44 Gy
      in 2-Gy fractions. Normal tissue dosimetric comparisons were made for the lung,
      heart, and esophagus. RESULTS: IMRT decreased incidental dose to the lungs,
      heart, and esophagus. For lung, both V20 Gy (21.5% vs 26.5%, P < .01) and mean
      lung dose (11.9 Gy vs 14.9 Gy, P < .01) were improved with IMRT without a
      corresponding increase in V5 Gy (P = .76). For heart, there was improvement in V5
      (28.9% vs 33.7%, P < .01) but no difference in V30 Gy (9.8% vs 15.9%. P = .10).
      For esophagus, all dosimetric endpoints were improved (V20 Gy, V45 Gy, V60 Gy,
      mean dose). For example, V60 was 6.5% with IMRT compared with 21% with 3D-CRT (P
      < .01). CONCLUSIONS: IMRT significantly decreased unnecessary dose to critical
      organs with equivalent coverage of planning target volumes. IMRT may therefore
      improve the tolerability of therapy.

PMID- 28740911
TI  - Predictors of relapse and evaluation of the role of postoperative radiation
      therapy in a modern series of patients with surgically resected stage III (N2)
      non-small cell lung cancer.
AB  - PURPOSE: For patients with stage III (N2) non-small cell lung cancer (NSCLC)
      treated with surgical resection, postoperative chemotherapy improves overall
      survival (OS), but the role of postoperative radiation therapy (PORT) is
      controversial. The purpose of this study was to evaluate risk factors for local
      regional recurrence and to evaluate the impact of PORT on local-regional control
      (LRC) and OS in a modern series of patients with surgically resected stage III
      (N2) NSCLC. METHODS AND MATERIALS: A retrospective review was performed of
      patients with Stage III (N2) NSCLC who underwent curative intent resection at our
      institution between February 1999 and January 2012. OS, LRC, and metastasis-free
      survival were estimated from the date of surgery using the Kaplan Meier method.
      RESULTS: A total of 71 patients were included in the study. Patient median age
      was 63 years. Histology was adenocarcinoma in 69% of patients. Pretreatment
      positron emission tomography/computed tomography staging was performed for 90% of
      patients, and preoperative chemotherapy was administered in 23%. The rate of R0
      resection was 96%. Forty-one patients (58%) received PORT and the median PORT
      dose was 50 Gy (range, 41.4-60 Gy). The median follow-up time for living patients
      was 5.0 years. Five-year OS for all patients was 66%. OS at 5 years for patients
      who received PORT compared with patients who did not receive PORT was 71% versus
      60%, respectively (hazard ratio [HR], 0.61; 95% CI, 0.30-1.44; P = .28). LRC at 5
      years for patients who received PORT compared with patients who did not receive
      PORT was 89% versus 76%, respectively (HR, 0.44; 95% CI, 0.13-1.45; P = .17).
      Factors associated with decreased LRC were male sex (P = .011) and primary tumor
      (pT) stage (pT3/4 vs. pT1/2, P = .006). Metastasis-free survival at 5 years for
      patients who received PORT compared with those who did not receive PORT was 62%
      versus 63%, respectively (HR, 1.07; 95% CI, 0.51-2.40; P = .86). CONCLUSIONS: In
      this modern series of patients with resected stage III (N2) NSCLC, patients who
      received PORT had higher rates of OS and LRC, but these differences were not
      statistically significant.

PMID- 28740912
TI  - Effect of variations in atelectasis on tumor displacement during radiation
      therapy for locally advanced lung cancer.
AB  - PURPOSE: Atelectasis (AT), or collapsed lung, is frequently associated with
      central lung tumors. We investigated the variation of atelectasis volumes during
      radiation therapy and analyzed the effect of AT volume changes on the
      reproducibility of the primary tumor (PT) position. METHODS AND MATERIALS: Twelve
      patients with lung cancer who had AT and 10 patients without AT underwent
      repeated 4-dimensional fan beam computed tomography (CT) scans during radiation
      therapy per protocols that were approved by the institutional review board.
      Interfraction volume changes of AT and PT were correlated with PT displacements
      relative to bony anatomy using both a bounding box (BB) method and change in
      center of mass (COM). Linear regression modeling was used to determine whether PT
      and AT volume changes were independently associated with PT displacement. PT
      displacement was compared between patients with and without AT. RESULTS: The mean
      initial AT volume on the planning CT was 189 cm3 (37-513 cm3), and the mean PT
      volume was 93 cm3 (12-176 cm3). During radiation therapy, AT and PT volumes
      decreased on average 136.7 cm3 (20-369 cm3) for AT and 40 cm3 (-7 to 131 cm3) for
      PT. Eighty-three percent of patients with AT had at least one unidirectional PT
      shift that was greater than 0.5 cm outside of the initial BB during treatment. In
      patients with AT, the maximum PT COM shift was >=0.5 cm in all patients and >1 cm
      in 58% of patients (0.5-2.4 cm). Changes in PT and AT volumes were independently
      associated with PT displacement (P < .01), and the correlation was smaller with
      COM (R2 = 0.58) compared with the BB method (R2 = 0.80). The median root mean
      squared PT displacement with the BB method was significantly less for patients
      without AT (0.45 cm) compared with those with AT (0.8cm, P = .002). CONCLUSIONS:
      Changes in AT and PT volumes during radiation treatment were significantly
      associated with PT displacements that often exceeded standard setup margins.
      Repeated 3-dimensional imaging is recommended in patients with AT to evaluate for
      PT displacements during treatment.

PMID- 28740913
TI  - Reirradiation with stereotactic body radiation therapy after prior conventional
      fractionation radiation for locally recurrent pancreatic adenocarcinoma.
AB  - PURPOSE: Locally recurrent pancreatic cancer after prior radiotherapy is a
      therapeutic challenge with limited treatment options. This study examines the
      safety and efficacy of stereotactic body radiation therapy (SBRT) for locally
      recurrent pancreatic adenocarcinoma after prior conventional fractionation
      radiotherapy (CRT). METHODS AND MATERIALS: Outcomes from all patients treated
      with SBRT for locally recurrent pancreatic adenocarcinoma after prior CRT at our
      institution were reviewed. A total of 23 patients were identified. Prior CRT
      median dose was 50.4 Gy (range, 30-60 Gy). Twelve patients (52%) had previously
      undergone surgery and received CRT as neo- or adjuvant treatment. Nine patients
      (39.1%) were reirradiated with SBRT with a dose of 25 Gy in a single fraction,
      and 14 patients (60.8%) received a 5-fraction SBRT schedule with a median dose of
      25 Gy (range, 20-33 Gy) in 5 fractions (1-5 fractions). RESULTS: Median follow-up
      time was 28 months (range, 9-77 months). The median planning target volume was 46
      cm3 (range, 14-89 cm3). Median overall survival from diagnosis and from
      reirradiation were 27.5 months (range, 10-77 months) and 8.5 months (range, 1
      month to not reached) respectively. The cumulative incidence of local failures at
      the last follow-up was 19%. For the 4 patients who presented with local failure,
      one was treated with a single fraction of 25 Gy, and the other 3 were treated
      with 25 Gy in 5 fractions. Three patients presented regional failure, with a
      cumulative incidence of 14%, all with concurrent distant progression. The
      cumulative incidence of distant progression was 64% at last follow-up. After
      reirradiation, 6 patients (26.1%) developed a grade 2 or 3 gastrointestinal
      toxicity, 4 of them occurring among patients treated with a single-fraction SBRT
      regimen. CONCLUSIONS: Our report shows that SBRT for reirradiation of locally
      recurrent pancreas adenocarcinoma is a feasible option with good local control
      and acceptable toxicity rates, especially with a multifraction schedule.

PMID- 28740914
TI  - Independent test of a model to predict severe acute esophagitis.
AB  - PURPOSE: Treatment planning factors are known to affect the risk of severe acute
      esophagitis during thoracic radiation therapy. We tested a previously published
      model to predict the risk of severe acute esophagitis on an independent data set.
      METHODS AND MATERIALS: The data set consists of data from patients who had
      recoverable treatment plans and received definitive radiation therapy for non
      small cell carcinoma of the lung at a single institution between November 2004
      and January 2010. Complete esophagus dose-volume and available clinical
      information was extracted using our in-house software. The previously published
      model was a logistic function with a combination of mean esophageal dose and use
      of concurrent chemotherapy. In addition to testing the previous model, we used a
      novel, machine learning-based method to build a maximally predictive model.
      RESULTS: Ninety-four patients (81.7%) developed Common Terminology Criteria for
      Adverse Events, Version 4, Grade 2 or more severe esophagitis (Grade 2: n = 79
      and Grade 3: n = 15). Univariate analysis revealed that the most statistically
      significant dose-volume parameters included percentage of esophagus volume
      receiving >=40 to 60 Gy, minimum dose to the highest 20% of esophagus volume
      (D20) to D35, and mean dose. Other significant predictors included concurrent
      chemotherapy and patient age. The previously published model predicted risk
      effectively with a Spearman's rank correlation coefficient (rs) of 0.43 (P <
      .001) with good calibration (Hosmer-Lemeshow goodness of fit: P = .537). A new
      model that was built from the current data set found the same variables, yielding
      an rs of 0.43 (P < .001) with a logistic function of 0.0853 * mean esophageal
      dose [Gy] + 1.49 * concurrent chemotherapy [1/0] - 1.75 and Hosmer-Lemeshow P =
      .659. A novel preconditioned least absolute shrinkage and selection operator
      method yielded an average rs of 0.38 on 100 bootstrapped data sets. CONCLUSIONS:
      The previously published model was validated on an independent data set and
      determined to be nearly as predictive as the best possible two-parameter logistic
      model even though it overpredicted risk systematically. A novel, machine learning
      based model using a bootstrapping approach showed reasonable predictive power.

PMID- 28740915
TI  - Limited short-term effect of palliative radiation therapy on quantitative
      computed tomography-derived bone mineral density in femora with metastases.
AB  - PURPOSE: The aim of this study was to determine the effect of single fraction
      (SF) and multiple fraction (MF) radiation therapy (RT) on bone mineral density
      (BMD) in patients with cancer and bone metastases in the proximal femur. We
      studied this effect in the radiation field and within metastatic lesions, and
      differentiated between lytic, blastic, and mixed lesions. METHODS AND MATERIALS:
      This prospective cohort study comprised 42 patients with painful bone metastases,
      including 47 irradiated femora with 52 metastatic lesions in the proximal femur.
      Patients received either 8 Gy SF or 20 to 24 Gy in 5 to 6 fractions (MF).
      Quantitative computed tomography scans were obtained before RT and 4 and 10 weeks
      after the initial scan. Patients who received MF additionally underwent
      quantitative computed tomography on the final day of their treatment. Automated
      image registration was performed. Mean BMD was determined at each time point for
      each proximal femur (region of interest [ROI]-PF) and in greater detail for a
      region of interest that contained the metastatic lesion (ROI-ML). Statistical
      analysis was performed using linear mixed models. RESULTS: No significant
      differences in mean BMD were found between SF or MF RT over all time points in
      both ROI-PF and ROI-ML. Mean BMD did not change in ROI-PF with lytic and mixed
      lesions, but mean BMD in ROI-PF with blastic lesions increased to 109%.
      Comparably, when focused on ROI-ML, no differences in mean BMD were observed in
      lytic ROI-ML but mean BMD in mixed and blastic ROI-ML increased up to 105% and
      121%, respectively. CONCLUSIONS: Ten weeks after palliative radiation therapy in
      patients with femoral metastatic lesions, a limited increase in BMD was seen with
      no beneficial effect of MF over SF RT. BMD in lytic lesions was unchanged but
      slightly increased in mixed and blastic lesions.

PMID- 28740917
TI  - Phase 1 trial of preoperative image guided intensity modulated proton radiation
      therapy with simultaneously integrated boost to the high risk margin for
      retroperitoneal sarcomas.
AB  - PURPOSE: To conduct phase 1 and 2 trials with photon intensity modulated
      radiation therapy and intensity modulated proton therapy (IMPT) arms to
      selectively escalate the retroperitoneal sarcoma preoperative radiation dose to
      tumor volume (clinical target volume [CTV] 2) that is judged to be at a high risk
      for positive margins and aim to reduce local recurrence. We report on the IMPT
      study arm in phase 1. METHODS AND MATERIALS: Patients aged >=18 years with
      primary or locally recurrent retroperitoneal sarcoma were treated with
      preoperative IMPT, 50.4 GyRBE in 28 fractions, to CTV1 (gross tumor volume and
      adjacent tissues at risk of subclinical disease) with a simultaneous integrated
      boost to CTV2 to doses of 60.2, 61.6, and 63.0 GyRBE in 28 fractions of 2.15,
      2.20, and 2.25 GyRBE, respectively. The primary objective of the phase 1 study
      was to determine the maximum tolerated dose to CTV2, which will be further tested
      in the phase 2 study. RESULTS: Eleven patients showed increasing IMPT dose levels
      without acute dose limiting toxicities that prevented dose escalation to maximum
      tolerated dose. Acute toxicity was generally mild with no radiation
      interruptions. No unexpected perioperative morbidity was noted. Eight months
      postoperatively, one patient developed hydronephrosis that was treated by stent
      with ureter dissected off tumor and received 57.5 GyRBE. Retained ureter(s) was
      (were) subsequently constrained to 50.4 GyRBE without further problem. With an 18
      month median follow-up, there were no local recurrences. CONCLUSIONS: IMPT dose
      escalation to CTV2 to 63 GyRBE was achieved without acute dose limiting
      toxicities. The phase 2 study of IMPT will accrue patients to that dose. Parallel
      intensity modulated radiation therapy phase 1 arm is currently accruing at the
      initial dose level. Ureters that undergo a high dose radiation and/or surgery are
      at risk for late hydro-ureter. Future studies will constrain retained ureters to
      50.4 GyRBE to avoid ureteral stricture.

PMID- 28740918
TI  - Impact of moving target on measurement accuracy in 3D and 4D PET imaging-a
      phantom study.
AB  - PURPOSE: The purpose of this study was to evaluate the impact of tumor motion on
      maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV)
      measurements in both 3-dimensional and respiratory-correlated, 4-dimensional
      positron emission tomography (PET) imaging. We also evaluated the effect of
      implementing different attenuation correction methods in 4-dimensional PET image
      reconstruction on SUVmax and MTV. METHODS AND MATERIALS: An anthropomorphic
      thorax phantom with a spherical ball as a surrogate for a tumor was used.
      Different types of motion were imposed on the ball to mimic a patient's breathing
      motion. Three-dimensional PET imaging of the phantom without tumor motion was
      performed and used as the reference. The ball was then set in motion with
      different breathing motion traces and imaged with both 3- and 4-dimensional PET
      methods. The clinical 4-dimensional PET imaging protocol was modified so that 3
      different types of attenuation correction images were used for reconstructions:
      the same free-breathing computed tomography (CT) for all PET phases, the same
      average intensity projection CT for all PET phases, and 4-dimensional CT for
      phase-matched attenuation correction. Tumor SUVmax and MTV values that were
      measured from the moving phantom were compared with the reference values.
      RESULTS: SUVmax that was measured in 3-dimensional PET imaging was different from
      the reference value by 20.4% on average for the motions that were investigated;
      this difference decreased to 2.6% with 4-dimensional PET imaging. The measurement
      of MTV in 4-dimensional PET also showed a similar magnitude of reduction of
      deviation compared with 3-dimensional PET. Four-dimensional PET with use of phase
      matched 4-dimensional CT for attenuation correction showed less variation in
      SUVmax and MTV among phases compared with 4-dimensional PET with free-breathing
      CT or average intensity projection CT for attenuation correction. CONCLUSIONS:
      Four-dimensional PET imaging reduces the impact of motion on measured SUVmax and
      MTV when compared with 3-dimensional PET imaging. Clinical 4-dimensional PET
      imaging protocols should consider phase-matched 4-dimensional CT imaging for
      attenuation correction to achieve more accurate measurements.

PMID- 28740916
TI  - ACR Appropriateness Criteria(r) external beam radiation therapy treatment
      planning for clinically localized prostate cancer, part I of II.

PMID- 28740919
TI  - Palliative radiation therapy for superior vena cava syndrome in metastatic Wilms
      tumor using 10XFFF and 3D surface imaging to avoid anesthesia in a pediatric
      patient-a teaching case.

PMID- 28740920
TI  - Pathologic response after neoadjuvant chemotherapy predicts locoregional control
      in patients with triple negative breast cancer.
AB  - PURPOSE: Our goal was to determine the impact of pathologic response after
      neoadjuvant chemotherapy in triple negative breast cancer (TNBC) on the
      subsequent risk of locoregional recurrence (LRR) and disease-free survival (DFS)
      in the setting of adjuvant radiation therapy. METHODS AND MATERIALS: This was an
      institutional review board-approved retrospective chart review of patients with
      clinical stage I-III breast cancer treated with neoadjuvant chemotherapy, local
      surgery (breast conservation or mastectomy), and adjuvant radiation therapy
      between 1997 and 2015. Medical records were reviewed for clinical stage, tumor
      grade and subtype, neoadjuvant chemotherapy regimen, type of surgery, pathologic
      stage, use of radiation therapy, date and location of recurrence, and date of
      death. Molecular subtypes were defined using immunohistochemistry and histologic
      grade. ypT0 and ypN0 were defined as no residual invasive disease in breast or
      nodes, respectively. LRR was defined as any failure within the breast, chest
      wall, or regional lymph nodes. Statistical analysis was performed; LRR and DFS
      rates over 30 months were determined from Kaplan-Meier plots. RESULTS: Ninety
      four patients with TNBC were analyzed, of whom 72 received radiation therapy.
      This subgroup was isolated for further investigation. Median follow-up was 32.5
      months in this group. The pathologic complete response (pCR) rate was 36%, and
      presence or absence of disease in breast and/or nodes was significantly
      predictive of LRR. In TNBC patients who received radiation therapy, 30-month LRR
      was 22% in 41 patients with ypT+ versus 0% in 31 patients with ypT0 (P = .003),
      23% in 31 patients with ypN+ versus 5% in 41 patients with ypN0 (P = .016), and
      20% in 46 patients with residual disease in breast or nodes versus 0% in 26
      patients with pCR (P = .015). The difference in the rate of LRR between those who
      underwent lumpectomy versus mastectomy did not reach significance (8% vs 17%,
      respectively). Furthermore, patients with residual disease had a higher rate of
      DFS events (hazard ratio, 3.58; 95% confidence interval, 1.37-9.41; P = .006).
      The difference in DFS was not significantly associated with the type of surgery
      received. CONCLUSIONS: Patients with TNBC treated with neoadjuvant chemotherapy
      who have residual disease in the breast or lymph nodes at the time of surgery
      have significantly higher rates of locoregional failure and lower DFS compared
      with those with a pCR despite the use of adjuvant radiation therapy. Strategies
      to intensify therapy for patients with residual disease warrant further
      investigation.

PMID- 28740921
TI  - Long-term outcomes and toxicities of a large cohort of anal cancer patients
      treated with dose-painted IMRT per RTOG 0529.
AB  - PURPOSE: To describe the outcomes and toxicities of the largest cohort to date of
      patients with anal squamous cell carcinoma uniformly treated with concurrent
      chemoradiation using dose-painted intensity modulated radiation therapy (DP-IMRT)
      according to RTOG 0529. METHODS AND MATERIALS: We identified 99 eligible patients
      with anal cancer who were treated at our institution with definitive
      chemoradiation using DP-IMRT between 2005 and 2015 per RTOG 0529 dosing
      guidelines. Primary study endpoints included event-free survival (defined as
      recurrence, colostomy, or death) and overall survival. Secondary endpoints were
      treatment duration and acute and late toxicity. RESULTS: At a median follow-up of
      49 months (range, 2-114 months), 92% of patients had a clinical complete
      response. Fifteen percent underwent colostomy, including 4 pretreatment
      colostomies, 6 planned abdominoperineal resections (APRs), 4 salvage APRs, and 1
      APR for treatment-related complications. Thirteen patients developed local
      recurrence, of whom 6 developed synchronous metastatic disease. The 4-year
      overall survival was 85.8%, and 4-year event-free survival was 75.5%. Median
      treatment duration was 43 days (range, 10-68 days). The overall rate of non
      hematologic grade 3+ acute and grade 2+ late toxicities was 20% and 15%,
      respectively. CONCLUSIONS: Long-term outcomes and tolerability were excellent In
      the largest cohort to date of patients with anal cancer who received DP-IMRT
      prescribed per RTOG 0529.

PMID- 28740922
TI  - Serum lipidomic study reveals potential early biomarkers for predicting response
      to chemoradiation therapy in advanced rectal cancer: A pilot study.
AB  - PURPOSE: Prospective detection of patients with advanced rectal cancer (LARC) who
      have a higher probability of responding to preoperative chemoradiotherapy (CRT)
      may provide individualized therapy. Lipidomics is an emerging science dedicated
      to the characterization of lipid fingerprint involved in different pato
      physiological conditions. The purpose of this study is to highlight a typical
      lipid signature able to predict the tumor response to CRT. EXPERIMENTAL DESIGN: A
      prospective global analysis of lipids in 54 sera from 18 LARC patients treated
      with preoperative CRT was performed. Samples were collected at 3 time points:
      before (T0), at 14th day and at 28th day of CRT. An open LC-MS/MS analysis was
      performed to characterize lipid expression at T0. Differential lipids were
      validated by an independent approach and studied during treatment. RESULTS: From
      65 differential lipids highlighted between responder (RP) vs not responder (NRP)
      patients, five lipids were validated to predict response at T0: SM(d18:2/18:1),
      LysoPC (16:0/0:0), LysoPC (15:1(9z)/0:0), Lyso PE (22:5/0:0) and m/z= 842.90
      corresponding to a PC containing 2 fatty acids of 40 carbons totally. The levels
      of these lipids were lower in NRP before treatment. The ROC curve obtained by
      combining these five lipid signals showed an AUC of 0.95, evidence of good
      sensitivity and specificity in discriminating groups. CONCLUSION: Our results are
      in agreement with previous evidences about the role of lipids in determining the
      tumor response to therapy and suggest that the study of serum lipid could
      represent a useful tool in prediction of CRT response and in personalizing
      treatment.

PMID- 28740923
TI  - A comparison of interfraction setup error, patient comfort, and therapist
      acceptance for 2 different prostate radiation therapy immobilization devices.
AB  - PURPOSE: Our purpose was to investigate interfraction setup error of the
      immobilization device required to implement transperineal ultrasound compared
      with the current, standard immobilization device. Patient comfort and radiation
      therapist (RT) satisfaction were also assessed. METHODS AND MATERIALS: Cone beam
      computed tomography images were acquired before 4069 fractions from 111 patients
      (control group, n = 56; intervention group, n = 55) were analyzed. The
      intervention group was immobilized using the Clarity Immobilization System (CIS),
      comprising a knee rest with autoscan probe kit and transperineal ultrasound probe
      (n = 55), and control group using a leg immobilizer (LI) (n = 56). Interfraction
      setup errors were compared for both groups. Weekly questionnaires using a 10
      point visual analog scale were administered to both patient groups to measure and
      compare patient comfort. RT acceptance for both devices was also compared using a
      survey. RESULTS: There was no significant difference in the magnitude of
      interfraction cone beam computed tomography-derived setup shifts in the lateral
      and anteroposterior direction between the LI and CIS (P = .878 and .690,
      respectively). However, a significant difference (P = .003) was observed in the
      superoinferior direction between the 2 groups of patients. Patient-reported level
      of comfort and stability demonstrated no significant difference between groups (P
      = .994 and .132). RT user acceptance measures for the LI and CIS were ease of
      handling (100% vs 53.7%), storage (100% vs 61.1%), and cleaning of the devices
      (100% vs 64.8%), respectively. CONCLUSIONS: The CIS demonstrated stability and
      reproducibility in prostate treatment setup comparable to LI. The CIS device had
      no impact on patient comfort; however, RTs indicated a preference for LI over the
      CIS mainly because of its weight and bulkiness.

PMID- 28740924
TI  - Sociodemographic disparities in the utilization of proton therapy for prostate
      cancer at an urban academic center.
AB  - PURPOSE: Despite increasing use, proton therapy (PT) remains a relatively limited
      resource. The purpose of this study was to assess clinical and demographic
      differences in PT use for prostate cancer compared to intensity modulated
      radiation therapy (IMRT) at a single institution. METHODS AND MATERIALS: All
      patients with low- and intermediate-risk prostate cancer (N = 633) who underwent
      definitive radiation therapy between 2010 and 2015 were divided into PT (n = 508)
      and IMRT (n = 125) comparison groups and compared using chi2 and independent
      sample t tests. Univariable and multivariable logistic regression analyses were
      conducted to assess the associations between PT use and demographic, clinical,
      and treatment characteristics. RESULTS: The PT and IMRT cohorts varied by age,
      race, poverty, distance, treatment year, and treating physician. Patients who
      underwent IMRT were more likely to be older (mean age, 66 vs. 68 years), black
      (51% vs. 75%), and living in poverty or close to the facility (mean distance
      between residence and facility, 90 vs. 21 miles; P < .05). Prostate-specific
      antigen, prostate volume, and International Index of Erectile Function were
      significantly higher in the IMRT cohort (P < .05), but insurance type, risk
      group, tumor stage, Gleason score, and patient-reported urinary and bowel scores
      did not differ significantly (P > .05). Patients who underwent PT were more
      likely to receive hypofractionated therapy and less likely to receive androgen
      deprivation therapy (P < .01). On multivariable analysis, black (odds ratio [OR],
      0.29; 95% confidence interval [CI], 0.15-0.57) and other race (OR, 0.42; 95% CI,
      0.20-0.90); distance (OR, 1.14; 95% CI, 1.06-1.24); treatment years 2011 (OR,
      4.87; 95% CI, 2.23-10.6), 2012 (OR, 8.27; 95% CI, 3.43-19.9), and 2014 (OR, 4.44;
      95% CI, 1.94-10.2) relative to 2010; and a single treating physician (OR, 0.38;
      95% CI, 0.18-0.81) relative to the reference physician with the highest rate of
      use were associated with PT use, whereas clinical factors such as prostate
      specific antigen, prostate volume, International Index of Erectile Function, and
      androgen deprivation therapy were not. CONCLUSION: Sociodemographic disparities
      exist in PT use for prostate cancer at an urban academic institution. Further
      investigation of potential barriers to access is warranted to ensure equitable
      distribution across all demographic groups.

PMID- 28740925
TI  - Characterization of efficacy and toxicity after high-dose pelvic reirradiation
      with palliative intent for genitourinary second malignant neoplasms or local
      recurrences after full-dose radiation therapy in the pelvis: A high-volume cancer
      center experience.
AB  - PURPOSE: The use of large-field external beam reirradiation (re-RT) after pelvic
      radiation therapy (RT) for genitourinary (GU) cancers has not been reported. We
      report the results of such treatment in patients with either symptomatic GU
      second malignant neoplasms or locally recurrent pelvic tumors after initial RT
      for whom surgery or further systemic therapy was not an option. METHODS AND
      MATERIALS: The records of 28 consecutive patients with advanced, bulky GU
      malignancies treated with high-dose, large-field re-RT with palliative intent
      between 2008 and 2014 were retrospectively reviewed. Descriptive outcome analyses
      focused on toxicities and symptom control, and responses were evaluated by 2
      independent observers. RESULTS: Twenty-seven male patients (96%) were included.
      Median initial external beam RT dose was 64 Gy (range, 30-75.6 Gy). The median
      time between initial RT and re-RT was 9.5 years (range, 0.2-32 years). At the
      time of re-RT, there were 16 local recurrences and 12 second malignant neoplasms
      together comprising 16 bladder, 10 prostate, 1 ureteral, and 1 penile cancer.
      Indications for re-RT were pain and bleeding/hemorrhage. The median equivalent
      sphere diameter planning target volume for re-RT was 8.6 cm (range, 4.7-16.3 cm).
      Given the severity of the symptoms and the bulk of the disease at the time of re
      RT, a higher dose of RT was administered. The median re-RT dose was 50 Gy (range,
      27.5-66 Gy). For patients who received <60 Gy, hypofractionation of 250 cGy was
      used. The median cumulative dose was 113.9 Gy (range, 81.5-132.8 Gy). Re-RT was
      well tolerated with no Radiation Therapy Oncology Group grade 3-4 toxicities.
      Twenty-four patients (92%) had complete resolution of symptoms, and relief was
      durable in 67% of patients. The median overall survival was 5.8 months (range,
      0.3-38.9 months). Of those patients who are still alive, 100% remain free of
      initial symptoms. CONCLUSION: This small series suggests that aggressive re-RT of
      inoperable and symptomatic GU malignancies that is undertaken with meticulous
      treatment planning is well tolerated and provides excellent, durable relief
      without undue short-term toxicity. Validation in a larger prospective cohort is
      required.

PMID- 28740926
TI  - Intensity modulated radiation therapy for squamous cell carcinoma of the vulva:
      Treatment technique and outcomes.
AB  - OBJECTIVE: The objective of this study was to present the treatment technique and
      evaluate clinical outcomes after intensity modulated radiation therapy (IMRT) for
      vulvar cancer. METHODS AND MATERIALS: This retrospective study included 39
      patients with squamous cell carcinoma of the vulva treated with IMRT from 2005 to
      2015. There were 21 patients treated with postoperative IMRT, 13 with definitive
      IMRT, and 5 with preoperative IMRT. Tumor staging was Federation of Gynecology
      and Obstetrics stage I in 6, stage II in 7, stage III in 19, and stage IV in 7
      patients. Concurrent chemotherapy was administered to 14 patients. Brachytherapy
      was delivered in 8 patients. RESULTS: The median follow-up was 34 months (range,
      3.3-71). Median IMRT dose to patients receiving pre- or postoperative IMRT was
      5040 cGy (range, 5040-6080). Median combined IMRT and brachytherapy dose to gross
      tumor was 7000 cGy (range, 5040-7520) in those treated with definitive RT. The 3
      year locoregional control (LRC) and overall survival for those receiving
      postoperative RT were 89% and 67%, respectively. The 3-year LRC and overall
      survival for those receiving definitive IMRT were 42% and 49%, respectively. In
      patients receiving definitive or neoadjuvant IMRT, 69% had complete clinical
      response and 44% had complete pathologic response. The actuarial 3-year inguinal
      recurrence rate was 7%. There were no acute grade 3-4 hematological,
      gastrointestinal, or genitourinary toxicities. There were no late grade 3-4
      gastrointestinal or genitourinary toxicities. CONCLUSIONS: IMRT for vulvar cancer
      is associated with high rates of LRC in the postoperative setting and limited
      radiation-related toxicity. Durable LRC of disease after definitive IMRT remains
      challenging, and several refinements to our treatment technique are suggested.

PMID- 28740927
TI  - Adjuvant radiation for salivary gland malignancies is associated with improved
      survival: A National Cancer Database analysis.
AB  - OBJECTIVE: There are no randomized data to support the use of postoperative
      radiation for salivary gland malignancies. This study uses the National Cancer
      Database (NCDB) to describe the epidemiology of salivary gland cancer patients
      and to investigate whether treatment with adjuvant radiation improves overall
      survival. METHODS AND MATERIALS: A total of 8243 patients diagnosed with a major
      salivary gland cancer were identified from the NCDB. All patients received
      primary surgical resection of their malignancy. Patients were risk-stratified by
      adverse features, and overall survival rates were determined. Patients were
      considered high risk if they had extracapsular extension and/or positive margin
      after resection. Patients were considered intermediate risk if they did not meet
      the criteria for high risk but had pT3-T4 disease, pN+ disease, lymphovascular
      space invasion, adenoid cystic histology, or grade 2-3 disease. Patients who did
      not meet criteria for high or intermediate risk were considered low risk. Overall
      patient demographics, disease characteristics, treatment factors, and outcomes
      were summarized with descriptive statistics and analyzed with STATA. RESULTS:
      Median follow-up in this cohort was 42.4 months, with the median age of 58 years.
      Patients in the high-risk group had greater survival (hazard ratio [HR], 0.76; P
      = .002; 95% confidence interval [CI], 0.64-0.91) if they received adjuvant
      radiation therapy. In contrast, patients in the intermediate- (HR, 1.01; P =
      .904; 95% CI, 0.85-1.20) and low-risk groups (HR, 0.85; P = .427; 95% CI, 0.57
      1.26) did not experience a survival benefit with adjuvant radiation therapy.
      CONCLUSIONS: This large analysis compared survival outcomes between observation
      and adjuvant radiation alone in risk-stratified patients after resection of major
      salivary glands using a national database. The use of adjuvant radiation for high
      risk major salivary gland cancers appears to offer a survival benefit. Although
      an overall survival benefit was not seen in low- and intermediate-risk salivary
      gland cancers, this study could not address impact on local control because of
      the limitations of the NCDB.

PMID- 28740928
TI  - Magnetic resonance imaging guided reirradiation of recurrent and second primary
      head and neck cancer.
AB  - PURPOSE: To report a single-institutional experience using magnetic resonance
      imaging (MRI) guided radiation therapy for the reirradiation of recurrent and
      second cancers of the head and neck. METHODS AND MATERIALS: Between October 2014
      and August 2016, 13 consecutive patients with recurrent or new primary cancers of
      the head and neck that occurred in a previously irradiated field were
      prospectively enrolled in an institutional registry trial to investigate the
      feasibility and efficacy of MRI guided radiation therapy using a 0.35-T MRI
      scanner with a cobalt-60 radiation therapy source called the ViewRay system
      (ViewRay Inc., Cleveland, OH). Eligibility criteria included biopsy-proven
      evidence of recurrent or new primary squamous cell carcinoma of the head and
      neck, measurable disease, and previous radiation to >60 Gy. MRI guided
      reirradiation was delivered either using intensity modulated radiation therapy
      with conventional fractionation to a median dose of 66 Gy or stereotactic body
      radiation therapy (SBRT) using 7 to 8 Gy fractions on nonconsecutive days to a
      median dose of 40 Gy. Two patients (17%) received concurrent chemotherapy.
      RESULTS: The 1- and 2-year estimates of in-field control were 72% and 72%,
      respectively. A total of 227 daily MRI scans were obtained to guide
      reirradiation. The 2-year estimates of overall survival and progression-free
      survival were 53% and 59%, respectively. There were no treatment-related
      fatalities or hospitalizations. Complications included skin desquamation,
      odynophagia, otitis externa, keratitis and/or conjunctivitis, and 1 case of
      aspiration pneumonia. CONCLUSIONS: Our preliminary findings show that
      reirradiation with MRI guided radiation therapy results in effective disease
      control with relatively low morbidity for patients with recurrent and second
      primary cancers of the head and neck. The superior soft tissue resolution of the
      MRI scans that were used for planning and delivery has the potential to improve
      the therapeutic ratio.

PMID- 28740929
TI  - Preserving the legacy of reirradiation: A narrative review of historical
      publications.
AB  - PURPOSE: The purpose of this study is to illustrate the historical development of
      reirradiation during several decades of the 20th century, in particular between
      1920 and 1960. METHODS AND MATERIALS: We chose the format of a narrative review
      because the historical articles are heterogeneous. No systematic extraction of
      baseline data, treatment details, or follow-up care was possible in many cases.
      RESULTS: Both hematological malignancies and solid tumors were treated with a
      second course of radiation therapy, and indications included local relapse,
      regional nodal recurrence, and second primary tumors developing in a previously
      treated region. The literature consists of retrospective single-institution
      analyses describing treatment approaches that included external beam radiation
      therapy, brachytherapy, or combinations thereof. Data on toxicities and survival
      were often provided. Breast cancer and gynecological, head and neck, brain, and
      skin tumors are among the entities included in this review. CONCLUSIONS: The
      leading pioneers in the field are fully aware of many of the challenges we
      continue to debate today. These include the process of late tissue changes and
      development of personalized treatment approaches and better ways to select
      patients who are likely to benefit from a second course of radiation therapy.

PMID- 28740930
TI  - Functional image guided radiation therapy planning in volumetric modulated arc
      therapy for patients with malignant pleural mesothelioma.
AB  - PURPOSE: To investigate the incorporation of functional lung image-derived low
      attenuation area (LAA) based on 4-dimensional computed tomography (4D-CT) in
      volumetric modulated arc therapy (VMAT) planning for patients with malignant
      pleural mesothelioma (MPM) after extrapleural pneumonectomy. METHODS AND
      MATERIALS: Twelve patients with MPM after extrapleural pneumonectomy were
      included. The primarily affected side was the right in 6 patients and the left in
      6 patients. LAA was generated from 4D-CT data according to CT values with a
      threshold of less than -860 Hounsfield units (HU). Functional lung image was
      defined as the area where LAA was excluded from contralateral lung image. Two
      radiation therapy plans were designed: (1) Plan C, conventional VMAT and (2) Plan
      F, functional VMAT plan based on the functional lung. Both plans were compared in
      each patient with respect to the following dosimetric parameters: fV20, V20,
      fV10, V10, fV5, and V5, the percentages of functional or contralateral lung
      volumes irradiated with >20 Gy, 10 Gy, or 5 Gy, respectively; functional mean
      lung dose (fMLD) and mean lung dose (MLD), the mean dose to the functional or
      contralateral lung, respectively; maximum dose to the cord; mean doses to the
      liver and heart; and planning target volume homogeneity index. RESULTS: fV5 and
      MLD were significantly lower in Plan F (fV5, median 57.5% in Plan C vs 38.5% in
      Plan F, P < .01; MLD, median 7.0 Gy in Plan C vs 6.4 Gy in Plan F, P = .04).
      fV10, V5, and fMLD were also significantly lower in Plan F. Compared with Plan C,
      planning target volume homogeneity index and liver, heart, and cord doses were
      not significantly elevated in Plan F. CONCLUSIONS: Significant reductions in fV5,
      fV10, fMLD, V5, and MLD were achieved with the functional image guided VMAT plan
      without negative effects on other factors. LAA-based functional image guided
      radiation therapy planning in VMAT is a feasible method to spare the functional
      lung in patients with MPM.

PMID- 28740931
TI  - The relationship between cardiac radiation dose and mediastinal lymph node
      involvement in stage III non-small cell lung cancer patients.
AB  - PURPOSE: The results from Radiation Therapy Oncology Group (RTOG) 0617, a dose
      escalation trial that compared treatment with 60 Gy versus 74 Gy for patients
      with stage III non-small cell lung cancer (NSCLC), suggested that in these
      patients, the heart dose from radiation therapy correlates with survival. In
      particular, the study noted that patients with a high heart V5 and V30 had a
      poorer overall survival; however, the exact cause of this correlation is not
      known. We hypothesize that heart dose may be a surrogate for mediastinal nodal
      involvement, which has prognostic value in NSCLC. This study evaluates the
      relationship between heart dose and involvement of mediastinal lymph nodes in
      patients with stage III NSCLC treated with radiation therapy. METHODS AND
      MATERIALS: A total of 56 patients were identified and treated with definitive
      radiation therapy from 2007 to 2014. The heart was recontoured for every patient
      by a single physician, per the RTOG 1106 contouring atlas. We assessed lymph node
      station involvement using pretreatment data, and nodal coverage was confirmed on
      plan review. RESULTS: Mean heart dose was found to be significantly higher in
      patients with multinodal station and level 7 involvement. On Spearman's rank
      correlation, level 7 was significantly associated with all heart parameters
      tested (P < .001). Patients who had 2 or more lymph node stations involved were
      found to have significantly higher heart doses for all parameters tested when
      compared with those who had only one station involved or no nodal involvement.
      CONCLUSIONS: Our findings suggest that heart dose may be a surrogate for other
      prognostic factors in stage III NSCLC rather than an independent predictor of
      outcome.

PMID- 28740932
TI  - Importance of baseline PET/CT imaging on radiation field design and relapse rates
      in patients with Hodgkin lymphoma.
AB  - PURPOSE: This study analyzed the impact of pretreatment positron emission
      tomography/computed tomography (PET/CT) scans on involved site radiation therapy
      (ISRT) field design and pattern of relapse among patients with Hodgkin lymphoma
      (HL). METHODS AND MATERIALS: Thirty-seven patients with stage I or II HL who
      received first-line chemotherapy followed by consolidative ISRT to all initial
      sites of disease were enrolled in an institutional review board-approved outcomes
      tracking protocol between January 2009 and December 2014. Patients underwent
      standard-of-care follow-up. Relapse-free survival (RFS) was evaluated using a
      Kaplan-Meier analysis and cohort comparisons using a chi2 test. RESULTS: Thirty
      one patients underwent (PET/CT) scans before chemotherapy and 6 did not because
      of a lack of insurance (n = 2), inpatient chemotherapy administration (n = 2),
      scheduling conflicts (n = 1), and unknown reasons (n = 1). The median follow-up
      was 46 months, and the 4-year RFS rate was 92%. Patients without pretreatment PET
      imaging were more likely to experience disease relapse (4-year RFS, 97% vs. 67%;
      P = .001). Among the 6 patients who did not receive a baseline PET/CT scan, all 3
      recurrences occurred in lymph node regions outside of, but immediately adjacent
      to, the radiation field. CONCLUSIONS: Patients with stage I/II HL who receive
      ISRT without pretreatment PET/CT scans appear to have an increased risk for
      relapse in adjacent nodal stations just outside the radiation field. A larger
      cohort with a longer follow-up is needed to confirm these findings.

PMID- 28740933
TI  - 18F-FDG PET response and clinical outcomes after stereotactic body radiation
      therapy for metastatic melanoma.
AB  - BACKGROUND: Clinical data that support stereotactic body radiation therapy (SBRT)
      metastatic malignant melanoma (MM) are limited. Furthermore, functional imaging
      with 18F-fludeoxyglucose positron emission tomography (PET) may offer a more
      accurate post-SBRT assessment. Therefore, we assessed the clinical outcomes and
      metabolic response of metastatic MM after SBRT. METHODS AND MATERIALS: Patients
      with MM who were treated with SBRT and had pre- and post-PET scans (>1) were
      included in this study. A total of 390 pre- and post-SBRT PET/computed tomography
      (CT) scans for 80 metastases were analyzed. The PET metabolic response was
      evaluated per the PET Response Criteria in Solid Tumors (PERCIST), version 1.0,
      criteria. Single-fraction equivalent dose (SFED) was calculated as per the
      standard. The Kaplan-Meier method was used for estimates of overall survival (OS)
      and progression-free survival. The cumulative incidence method was used to
      estimate metastasis control (MC). A Wilcoxon test was used to compare survival
      estimates. The prognostic factors for MC and OS were assessed using the Cox
      proportional hazards model, and the Likelihood Ratio was also used for
      comparisons between groups. RESULTS: A median of 6 PET scans (range, 2-6 scans)
      was evaluated for each metastasis. The median SFED was 42.8 Gy (range, 18-56.4
      Gy) and the median biologically effective dose was 254.4 Gy2.5 (range, 100.8-540
      Gy2.5). Twenty percent of patients received chemotherapy and 59% received
      immunotherapy: granulocyte-macrophage colony-stimulating factor (64%) and
      ipilimumab (34%). MC was 94% and 90% at 1 year and 3 years, respectively. The OS
      was 74% and 27% and 1 year and 3 years, respectively. Complete response was
      achieved in 90% at a median of 2.8 months (range, 0.4-25.2 months). SFED >24 Gy
      correlated with improved MC (93% vs 75%, P = .01). Acute and late grade 3+
      toxicities were 4% and 11%, respectively, with no grade 5 toxicity. CONCLUSIONS:
      Post-SBRT PET/CT for extracranial metastatic MM resulted in high rates of
      complete response at a median of 2.8 months, and durable MC was achieved with
      SFED >24 Gy. SBRT, in addition to surgery and ablation, should be discussed with
      patients with MM, especially those with oligometastases.

PMID- 28740934
TI  - Patient-reported distress and survival among patients receiving definitive
      radiation therapy.
AB  - OBJECTIVE: Patient-reported distress (PRD) has not been well assessed in
      association with survival after radiation therapy (RT). The aims of this study
      were to evaluate the association between PRD level and survival after definitive
      RT and to identify the main causes of distress in definitive RT patients. METHODS
      AND MATERIALS: A total of 678 consecutive patients receiving definitive RT at our
      institution from April 2012 through May 2015 were included. All patients answered
      a PRD questionnaire that contained 30 items related to possible causes of
      distress, which could be rated from 1 (no distress) to 5 (high distress).
      Additionally, patients were asked to rate their overall distress level from 0 (no
      distress) to 10 (extreme distress). This overall distress level was our primary
      patient-reported distress measure and was examined as a continuous variable and
      as a categorical variable with 3 PRD levels (low, 0-3 [n = 295]; moderate, 4-6 [n
      = 222]; and high, 7-10 [n = 161]). RESULTS: As a continuous variable in
      multivariable Cox regression analysis, a higher overall PRD level was associated
      with poorer survival after RT (hazard ratio [HR], 1.39; P = .004). As a
      categorical variable, compared with patients with low distress, survival was
      poorer for patients with moderate distress (HR, 1.62; P = .038) or high distress
      (HR, 1.49; P = .12), but the latter difference was not significant. When the
      moderate and high distress levels were combined, survival was significantly
      poorer compared with the low distress level (HR, 1.57; P = .034). The top 5
      specific causes of distress that patients mentioned were "How I feel during
      treatment," "Fatigue," "Out-of-pocket medical costs," "Pain that affects my daily
      functioning," and "Sleep difficulties." CONCLUSIONS: PRD before or during RT is a
      prognostic factor associated with decreased survival. Distress screening
      guidelines and interventions should be implemented for patients receiving
      definitive RT.

PMID- 28740935
TI  - Effects of vertebral-body-sparing proton craniospinal irradiation on the spine of
      young pediatric patients with medulloblastoma.
AB  - PURPOSE: To investigate the long-term effects of vertebral-body-sparing proton
      craniospinal irradiation (CSI) on the spine of young patients with
      medulloblastoma. METHODS AND MATERIALS: Six children between the ages of 3 and 5
      years with medulloblastoma were treated with vertebral-body-sparing proton CSI
      after maximal safe resection. Radiation therapy was delivered in the supine
      position with posterior beams targeting the craniospinal axis, and the proton
      beam was stopped anterior to the thecal sac. Patients were treated with a dose of
      either 23.4 Gy or 36 Gy to the craniospinal axis followed by a boost to the
      posterior fossa and any metastatic lesions. Chemotherapy varied by protocol.
      Radiographic effects on the spine were evaluated with serial imaging, either with
      magnetic resonance imaging scans or plain film using Cobb angle calculations, the
      presence of thoracic lordosis, lumbar vertebral body-to-disc height ratios, and
      anterior-posterior height ratios. Clinical outcomes were evaluated by
      patient/family interview and medical chart review. RESULTS: Overall survival and
      disease free survival were 83% (5/6) at follow-up. Median clinical and
      radiographic follow-up were 13.6 years and 12.3 years, respectively. Two patients
      were clinically diagnosed with scoliosis and treated conservatively. At the time
      of follow-up, no patients had experienced chronic back pain or required spine
      surgery. No patients were identified to have thoracic lordosis. Diminished growth
      of the posterior portions of vertebral bodies was identified in all patients,
      with an average posterior to anterior ratio of 0.88, which was accompanied by
      compensatory hypertrophy of the posterior intervertebral discs. CONCLUSION:
      Vertebral-body-sparing CSI with proton beam did not appear to cause increased
      severe spinal abnormalities in patients treated at our institution. This approach
      could be considered in future clinical trials in an effort to reduce toxicity and
      the risk of secondary malignancy and to improve adult height.

PMID- 28740936
TI  - Comparison of height and weight after 12 vs. 18 Gy cranial radiation therapy in
      pediatric acute lymphoblastic leukemia (ALL) patients.
AB  - PURPOSE: To compare the effect of 12 versus 18 Gy cranial radiation therapy (RT)
      on height and weight indices among pediatric patients with acute lymphoblastic
      leukemia (ALL). METHODS AND MATERIALS: Records of children with ALL who were 2 to
      14 years old at the time of RT and were treated at a single institution between
      2000 and 2011 were reviewed. Patients' height, weight, and body mass index were
      converted into z-scores using the Centers for Disease Control growth charts to
      normalize the values to number of standard deviations from the mean. These values
      were measured at the pre-RT clinic visit and subsequent yearly intervals. The z
      scores of the growth indices were fitted into a generalizing estimating equations
      model and analyzed by various clinical factors. RESULTS: A total of 48 patients
      met the study criteria, including 32 boys and 16 girls. The median age at the
      time of RT was 7 years (range, 2-14 years). Patients were separated into 2 dose
      groups: 12 Gy (n = 30) and 18 Gy (n = 18). Median follow-up was 4.9 years (range,
      3.0-11.8 years) and 6.0 years (range, 3.1-10.5 years) and the median pre-RT
      height z-scores were -0.55 (range, -2.2 to 1.4) and -0.85 (range, -3.1 to 0.8)
      for the 2 groups, respectively (P = .65). Patients who received 18 Gy had a
      significant difference in change in height compared with those who received 12
      Gy, who were able to maintain normal growth during the first 3 years of follow
      up. This did not appear to be sex-specific, and there was no difference in change
      in weight or body mass index. CONCLUSIONS: Compared with 18 Gy, patients with ALL
      who received 12 Gy of cranial RT had less height impairment in the first 3 years
      post-RT, but further prospective studies are needed.

PMID- 28740937
TI  - Impact of prone versus supine positioning on small bowel dose with pelvic
      intensity modulated radiation therapy.
AB  - PURPOSE: To report the results of a prospective study that compares small bowel
      doses during prone and supine pelvic intensity modulated radiation therapy.
      METHODS AND MATERIALS: Ten patients receiving pelvic radiation therapy each had 2
      intensity modulated radiation therapy plans generated: supine and prone on a
      belly board (PBB). Computed tomography on rails was performed weekly throughout
      treatment in both positions (10 scans per patient). After image fusion, doses to
      small bowel (SB) loops and clinical target volume were calculated for each scan.
      Changes between the planned and received doses were analyzed and compared between
      positions. The impact of bladder filling on SB dose was also assessed. RESULTS:
      Prone treatment was associated with significantly lower volumes of SB receiving
      >=20 Gy. On average, prone on a belly board positioning reduced the volume of SB
      receiving a given dose of radiation by 28% compared with supine positioning.
      Target coverage throughout the treatment course was similar in both positions
      with an average minimum clinical target volume dose of 88% of the prescribed
      prone dose and 89% of the supine (P = .54). For supine treatment, SB dose was
      inversely correlated with bladder filling (P = .001-.013; P > .15 for prone). For
      96% of treatments, the volume of SB that received a given dose deviated >10% from
      the plan. The deviation between the planned and delivered doses to SB did not
      differ significantly between the positions. CONCLUSIONS: Prone positioning on a
      belly board during pelvic IMRT consistently reduces the volume of SB that
      receives a broad range of radiation doses. Prone IMRT is associated with
      interfraction dose variation to SB that is similar to that of supine positioning.
      These findings suggest that prone positioning with daily image guided radiation
      therapy is an effective method for maximizing SB sparing during pelvic IMRT.

PMID- 28740938
TI  - WHOLE-BODY VIBRATION EXERCISE IS WELL TOLERATED IN PATIENTS WITH DUCHENNE
      MUSCULAR DYSTROPHY: A SYSTEMATIC REVIEW.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is caused by a defective gene
      located on the X-chromosome, responsible for the production of the dystrophin
      protein. Complications in the musculoskeletal system have been previously
      described in DMD patients. Whole body vibration exercise (WBVE) is a treatment
      that improves musculoskeletal function in movement disorders. The aim of this
      study was to review the effects of WBVE on functional mobility, bone and muscle
      in DMD patients. MATERIALS AND METHODS: Four databases were searched. Three
      eligible studies were found; all three conclude the management of DMD patients
      with WBV was clinically well tolerated. The studies used a side-alternating WBV
      system, frequencies 7 - 24 Hz; and amplitudes 2 - 4 mm. RESULTS: A work indicates
      that a temporary increase in creatine kinase in DMD during the first days of WBV
      was observed, but other authors did not find changes. No significant changes in
      bone mass, muscle strength or bone markers. Some patients reported subjective
      functional improvement during training. Interpretation. CONCLUSION: It is
      concluded that WBV seems to be a feasible and well tolerated exercise modality in
      DMD patients.

PMID- 28740939
TI  - EFFECT OF A SHORT PERIOD WHOLE BODY VIBRATION WITH 10 HZ ON BLOOD BIOMARKERS IN
      WISTAR RATS.
AB  - BACKGROUND: Exposure to whole body vibration exercises (WBVE), besides some
      biological effects, causes alterations in the concentration of some blood
      biomarkers. The aim of this study is to evaluate the action of vibration (10 Hz)
      of WBVE on the concentration of blood biomarkers in Wistar rats. MATERIALS AND
      METHODS: Wistar rats were divided in 2 groups. The experimental group (EG) was
      subjected to vibrations of 10Hz (one min per day, one week, total time of seven
      min), while the control group (CG) has not experienced vibration. Samples of
      whole blood were drawn for biochemical analysis of the concentration of total
      cholesterol, triglycerides, HDL, LDL, VLDL, glucose, CPK, albumin, alkaline
      phosphates, TGP, TGO, gammaGT, lipase, amylase, urea and creatinine. RESULTS:
      White blood cell count and a platelet-hemogram were also performed. Significant
      (p<0.05) increase in TGP, TGO and white blood cells and decrease in LDL
      concentration was found after exposure of 10Hz mechanical vibration. CONCLUSION:
      Although these findings were obtained with rats, they might contribute to try to
      understand better these mechanisms that occur following exposure to a frequency
      of 10Hz.

PMID- 28740940
TI  - RELEVANCE OF WHOLE BODY VIBRATION EXERCISE IN SPORT: A SHORT REVIEW WITH SOCCER,
      DIVER AND COMBAT SPORT.
AB  - BACKGROUND: Whole body vibration exercise (WBVE) has been used as a safe and
      accessible exercise and important reviews have been published about the use of
      this exercise to manage diseases and to improve physical conditions of athletes
      The aim of this paper is to highlight the relevance of WBVE to soccer players,
      divers and combat athletes. MATERIAL AND METHODS: This study was made through a
      systematic review of publications involving WBVE and the selected sports in two
      databases (Pubmed and PEDRo). RESULTS: It were identified 10 studies involving
      WBVE and sports (6 of soccer, 2 of diving and 2 of sport combat) with 156
      subjects (80 soccer players, 32 divers and 44 combat athletes), with age from 17
      to 44 years old. CONCLUSION: The use of WBVE has proven to be a safe and useful
      strategy to improve the physical conditions of players of different sports. These
      findings may have clinical relevance and should be considered as a strategy to be
      used to try improve the physical conditions of players.

PMID- 28740941
TI  - EFFECTS OF WHOLE BODY VIBRATION INTERVENTION ON HANDGRIP STRENGTH OF BRAZILIAN
      HEALTHY SOLDIERS.
AB  - BACKGROUND: Whole body vibration (WBV) exercises have been investigated as an
      alternative and complementary method to traditional resistance programs for
      fitness improvements in healthy subjects. Active militaries must have a high
      fitness level and have to improve some physical abilities to accomplish some
      specific tasks in Army, as climb ropes, climb walls and pull up. MATERIALS AND
      METHODS: Seven young and healthy soldiers from Brazilian Army were exposed to
      mechanical vibration in a push-up position, with different frequencies, as 25
      (first session), 30 (second session), 35 (third session), 40 (fourth session) and
      45 Hz (fifth session). The WBV intervention consisted of five WBV sessions over a
      consecutive two and a half-weeks period of time. A WBV session consisted of
      twenty bouts, each one with 10- second vibration, interspersed with 10 seconds of
      passive rest and 4 minutes pause after the first 10 bouts. Handgrip strength was
      measured, as proposed by American Society of Hand Therapists - ASHT, before and
      after the session using 25 Hz of frequency and 45 Hz of frequency (1st and 5th
      sessions). RESULTS: No significant results were found between groups. CONCLUSION:
      Intervention of WBV exercises with 25 and 45 Hz of frequency applied by hands of
      healthy and young soldiers had no significant results. Further investigations
      should focus on the efficacy of WBV in the improvement of handgrip strength of
      young and healthy people.

PMID- 28740942
TI  - ANTI-VIRAL EFFECTS OF MEDICINAL PLANTS IN THE MANAGEMENT OF DENGUE: A SYSTEMATIC
      REVIEW.
AB  - BACKGROUND: Dengue is considered as an important arboviral disease. Safe, low
      cost, and effective drugs that possess inhibitory activity against dengue virus
      (DENV) are mostly needed to try to combat the dengue infection worldwide.
      Medicinal plants have been considered as an important alternative to manage
      several diseases, such as dengue. As authors have demonstrated the antiviral
      effect of medicinal plants against DENV, the aim of this study was to review
      systematically the published research concerning the use of medicinal plants in
      the management of dengue using the PubMed database. MATERIALS AND METHODS: Search
      and selection of publications were made using the PubMed database following the
      guidelines of the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA statement). RESULTS: Six publications met the inclusion criteria
      and were included in the final selection after thorough analysis. CONCLUSION: It
      is suggested that medicinal plants' products could be used as potential anti-DENV
      agents.

PMID- 28740943
TI  - POTENTIAL EFFECTS OF WHOLE-BODY VIBRATION EXERCISES ON BLOOD FLOW KINETICS OF
      DIFFERENT POPULATIONS: A SYSTEMATIC REVIEW WITH A SUITABLE APPROACH.
AB  - BACKGROUND: The ability to control skin blood flow decreases with advancing age
      and some clinical disorders, as in diabetes and in rheumatologic diseases.
      Feasible clinical strategies such as whole-body vibration exercise (WBVE) are
      being used without a clear understanding of its effects. The aim of the present
      study is to review the effects of the WBVE on blood flow kinetics and its
      feasibility in different populations. MATERIAL AND METHODS: The level of evidence
      (LE) of selected papers in PubMed and/or PEDRo databases was determined. We
      selected randomized, controlled trials in English to be evaluated. RESULTS: Six
      studies had LE II, one had LE III-2 and one III-3 according to the NHMRC. A great
      variability among the protocols was observed but also in the assessment devices;
      therefore, more research about this topic is warranted. CONCLUSION: Despite the
      limitations, it is can be concluded that the use of WBVE has proven to be a safe
      and useful strategy to improve blood flow. However, more studies with greater
      methodological quality are needed to clearly define the more suitable protocols.

PMID- 28740944
TI  - EFFECT OF MECHANICAL VIBRATION GENERATED IN OSCILLATING/VIBRATORY PLATFORM ON THE
      CONCENTRATION OF PLASMA BIOMARKERS AND ON THE WEIGHT IN RATS.
AB  - BACKGROUND: Whole body vibration (WBV) exercise has been used in health sciences.
      Authors have reported that changes on the concentration of plasma biomarkers
      could be associated with the WBV effects. The aim of this investigation is to
      assess the consequences of exposition of 25 Hz mechanical vibration generated in
      oscillating/vibratory platform (OVP) on the concentration of some plasma
      biomarkers and on the weight of rats. MATERIALS AND METHODS: Wistar rats were
      divided into two groups. The animals of the Experimental Group (EG) were
      submitted to vibration (25 Hz) generated in an OVP with four bouts of 30 seconds
      with rest time of 60 seconds between the bouts. This procedure was performed
      daily for 12 days. The animals of the control group (CG) were not exposed to
      vibration. RESULTS: Our findings show that the WBV exercise at 25 Hz was not
      capable to alter significantly (p<0.05) the weight of the rats. A significant
      alteration in the concentrations of amylase was found. CONCLUSION: Our results
      indicate a modulation of the WBV exercise with vibration of 25 Hz of frequency
      (i) in the pathways related to the weight and (ii) in the concentration of some
      biomarkers, such as amylase.

PMID- 28740945
TI  - QUALITY OF LIFE OF PATIENTS WITH METABOLIC SYNDROME IS IMPROVED AFTER WHOLE BODY
      VIBRATION EXERCISES.
AB  - BACKGROUND: Whole body vibration exercises (WBVE) improve the quality of life
      (QoL) of different populations. Metabolic syndrome patients (MetS) may be favored
      by physical activity. Questionnaires are used to assess the QoL. The aim was to
      evaluate the QoL of patients with MetS that have undergone WBVE with a brief
      WHOQOL (WHOQOL-BREF). MATERIAL AND METHODS: MetS patients were randomly divided
      into three groups: (i) control group (CG), (ii) treated with WBVE once per week
      (WBVE1) and (iii) treated with WBVE twice per week (WBVE2). In the first session,
      the patient was sat in a chair in front of the platform with the feet on its base
      in 3 peak to peak displacements (2.5, 5.0 and 7.5 mm) and frequency of 5 Hz was
      used. From the second to the last session, patients were subjected to the same
      protocol, however they were standing on the base of the platform and the
      frequency was increased up to 14 Hz. The patients fulfilled the WHOQOL-BREF
      before the first and after the last sessions. Cronbach coefficients were
      determined to each domain of the WHOQOL-BREF and test Wilcoxon (p<0.05) was used.
      RESULTS: The patients of the WBVE1 group had improvements in the physical,
      psychological and environment domains while in the WBVE2, the improvements were
      in the physical and social relationships domain of the WHOQOL-BREF. CONCLUSION:
      It was observed that the WBVE in a protocol (one or two times per week) with a
      progressive and increased frequency improves the QoL of patients with MetS in
      different domains of the WHOQOL-BREF.

PMID- 28740946
TI  - Is it necessary to perform prophylactic cholecystectomy for all symptomatic
      gallbladder polyps diagnosed with ultrasound?
AB  - OBJECTIVE: The main aim of this study is to determine the necessity of
      cholecystectomy in patients with ultrasound diagnosed symptomatic polypoid
      lesions of the gallbladder. MATERIAL AND METHODS: The data of 82 patients with
      polypoid lesions of the gallbladder who had cholecystectomy between 2000 and 2012
      were analyzed retrospectively with preoperative ultrasound and histopathology
      results. RESULTS: The mean age was 48.05+/-11.18 years (range 25-74 years). All
      patients underwent preoperative ultrasound examination. Eighteen (22%) of the 82
      patients were asymptomatic; their polypoid lesions of the gallbladder were
      detected with ultrasound during a check-up or other reasons. In 45 (55%) of cases
      pathology reported no polypoid lesions of the gallbladder. Right upper quadrant
      or epigastric pain was the most common symptom (41.46%) that led to hepatobiliary
      ultrasound, the other symptom was dyspepsia (36.59%). On preoperative ultrasound
      evaluation, 22 patients had multiple polyps, and 9 of these 22 patients had at
      least 3 polyps. CONCLUSION: There is an inaccuracy of ultrasound to detect
      polypoid lesions of the gallbladder. After diagnosing polypoid lesions of the
      gallbladder by using standard ultrasound, further pre-operative diagnostic tests
      are needed to help discriminating benign lesions from malignant ones, which may
      prevent unnecessary surgery regardless of symptoms.

PMID- 28740947
TI  - Analysis of the publishing rate and the number of citations of general surgery
      dissertations.
AB  - OBJECTIVE: A dissertation is a scientific document. However, if it is not
      published in a scientific journal, it will gain access to only a limited audience
      and thus will be unable to achieve its objective. Nevertheless, the rate of
      publishing in journals is not high among dissertations. In this study, we aimed
      to investigate the publishing rates of general surgery dissertations in journals
      and the total number of citations. MATERIAL AND METHODS: All medical
      dissertations that have been prepared at general surgery departments of
      university hospitals and presented between the years 2006 and 2008 were analyzed.
      The authors checked whether the dissertations were published in a journal or not,
      by searching the dissertation in 4 different resources with the name of their
      authors. RESULTS: Two hundred and thirty-two dissertations were included. Half of
      those dissertations were experimental animal studies. Seventy dissertations were
      published in various journals. Fifty one (22%) of these were published in Science
      Citation Index Expanded journals, while 19 (8.1%) of them were published in
      Turkish non-Science Citation Index Expanded journals. There was no significant
      difference in terms of publishing rates between study types. The number of annual
      citations per article was 1.1. The writer of the dissertation was the first
      author in 35 (68,6%) articles. CONCLUSION: The publishing rates of dissertations
      in general surgery is low, with only 22% being published in Science Citation
      Index Expanded journals. The citation rate was also detected to be low in our
      study. Consequently, a dissertation should be considered as a scientific research
      study and planned as such, not as obligatory assignments. The publishing rates of
      dissertations should be increased, and authors should be led and encouraged to
      publish their dissertations.

PMID- 28740948
TI  - A rare case of Spigelian hernia combined with direct and indirect inguinal
      hernias.
AB  - Spigelian hernia is a rare type of ventral hernias with nonspecific symptoms and
      signs. Therefore, its diagnosis is often difficult and requires more clinical
      attention. Although intermittent abdominal swelling and pain are the main
      symptoms, Spigelian hernias can be sometimes asymptomatic and are discovered
      incidentally at the operation. In some cases, these hernias can be associated
      with other abdominal wall hernias, therefore a detailed physical examination of
      the patients is necessary to avoid mistakes in diagnosis. Herein, we report an
      interesting and educational case of Spigelian hernia with accompanying
      ipsilateral both direct and indirect inguinal hernias in a male patient treated
      by open surgical repair with use of polypropylene mesh.

PMID- 28740949
TI  - Good surgeon: A search for meaning.
AB  - The art and philosophy of surgery are not as often discussed as scientific
      discoveries and technological advances in the modern era of surgery. Although
      these are difficult to teach and pass on to the next generations of surgeons they
      are no less important for training good surgeons and maintaining their high
      standards. The authors of this review and opinion article tried to define what
      being a good surgeon really means and to look into the subject by analysing the
      essential conditions for being a good surgeon and the qualities that such a
      specialist should possess. In addition to a strong theoretic knowledge and
      practical skills and among the several described professional and personal
      characteristics, a good surgeon is expected to have common sense. It enables a
      surgeon to make a sound practical judgment independent of specialized medical
      knowledge and training. The possible ways of developing and/or enhancing common
      sense during surgical training and subsequent practice require separate analysis.

PMID- 28740950
TI  - Lymphedema: From diagnosis to treatment.
AB  - Lymphedema is a chronic and progressive disorder resulting from impaired
      lymphatic system function. In developed countries, upper extremity lymphedema is
      mainly the consequence of breast cancer surgery in which axillary lymph node
      dissection and radiation alter upper extremity lymphatic flow. Diagnosis of
      lymphedema is made clinically. Nevertheless, there are numerous diagnostic tools
      available for disease staging. Recently, a new technology namely magnetic
      resonance lymphangiography has emerged in the medical field to assist in both
      diagnosis and management. There are non-surgical and surgical treatment options
      available. Non-surgical methods are always the first-line treatment; however,
      surgical options can be explored in appropriate patients. Recent studies focus on
      the prevention of lymphedema using surgical techniques utilizing axillary reverse
      mapping to delineate arm lymphatics from axillary lymphatics. Finding the most
      suitable technique for each type of lymphedema with variable stages is one of the
      most complicated decisions for practitioners. More studies are needed to reveal
      the exact biology of lymphedema to ensure complete understanding of the disease
      and improve outcomes.

PMID- 28740951
TI  - A complication of thyroidectomy: Do not forget suture reaction.
AB  - OBJECTIVE: In this study, we aimed to present patients who have developed suture
      reaction and were treated in our clinic following thyroidectomy operation.
      MATERIAL AND METHODS: Patients who had been treated for suture reaction following
      thyroidectomy between January 2012 and December 2014 were retrospectively
      evaluated. The patients were analyzed in terms of their age, gender, duration of
      the symptoms, type of previous operation and treatment modality. RESULTS: Between
      January 2012 and December 2014, 559 thyroid/parathyroid operations were performed
      in our clinic. A total of 12 patients were admitted with suture reaction within
      this period thus yielding a suture reaction incidence of 2.1%. The mean age of
      these patients was 42+/-7.65 years, 75% of them were female while 25% of them
      were male. The types of previous operations were bilateral total thyroidectomy in
      83.3%, lobectomy in 8.3% and near total thyroidectomy in 8.3% of the patients.
      The mean symptom duration was 7.2+/-4.3 (2-16) months. Two patients (16.7%)
      underwent a second surgical operation for suture reaction, while 10 patients
      (83.3%) were treated conservatively. None of the patients developed
      complications. CONCLUSION: One of the most common complications that develop
      after thyroidectomy is bleeding. Ligation must be performed in order to prevent
      this complication. As it is known, surgical ligation with sutures may cause
      tissue reaction. Sutures that are absorbable and have a low risk for reaction
      formation should be chosen if suturing is preferred.

PMID- 28740952
TI  - Preventing oxygen free radical damage by proanthocyanidin in obstructive
      jaundice.
AB  - OBJECTIVE: Tissue damage and endotoxemia in obstructive jaundice are attributed
      to the increase in oxygen free-radicals. We aimed at evaluating the possible
      protective effect of grape seed proanthocyanidin extract (GSPE), which is a
      potent exogenous free-radical scavenger and antioxidant. MATERIAL AND METHODS:
      The study was performed at the Necmettin Erbakan University Meram School of
      Medicine Research and Application Center for Experimental Medicine Laboratory
      with ethical approval. 30 Wistar-Albino rats were used and were divided into 3
      groups. The common bile duct was identified and only dissected in the first group
      (sham). Following dissection of the common bile duct it was ligated with 4/0 silk
      just above the pancreas in the second group (control). After ligation of the
      common bile duct, 100mg/kg/day GSPE was administered via orogastric lavage for 10
      days in the third group. RESULTS: Biochemical values revealed a statistically
      significant difference between Group I and the others. There was no difference
      between Group II and III regarding biochemical values. There was a statistically
      significant difference, however, between Group II and III with regards to nitric
      oxide levels. There was a statistically significant difference between Group I
      and the other groups concerning hepatic and pulmonary tissue damage on
      histopathologic evaluation. There was no difference among the groups with regards
      to renal tubular damage. CONCLUSION: Proanthocyanidin is an effective natural
      antioxidant in decreasing the level of tissue damage caused by oxygen free
      radicals.

PMID- 28740953
TI  - Analysis of risk factors affecting coagulopathy after donor hepatectomy in a
      newly established liver transplant center.
AB  - OBJECTIVE: As might be expected, living donor liver surgery is associated with
      serious morbidity and mortality risks. Coagulopathy after donor hepatectomy is an
      important risk factor affecting morbidity. In this study, risk factors affecting
      the development of coagulopathy after donor hepatectomy was evaluated in a newly
      established liver transplant center. MATERIAL AND METHODS: A retrospective
      evaluation of 46 liver donors to whom hepatectomy was applied in Medipol
      Universty of School of Medicine Department of Organ Transplantation between April
      2014 and July 2015 was made. Coagulopathy was defined as prothrombin time >=15
      sec. or platelet count <80000/mm3 on postoperative day 3. Donors were separated
      into 2 groups as those with (n=24) and without (n=22) coagulopathy. Preoperative,
      intraoperative and postoperative factors acting on coagulopathy were analyzed.
      RESULTS: In the intergroup analysis, it was seen that remnant liver volume,
      remnant liver volume % and remnant liver volume to body weight ratio were factors
      associated with coagulopathy. The cut-off values for these 3 parameters were
      calculated as 773.5 cm3, 40.5% and 0.915 cm3/kg, respectively. Only remnant liver
      volume % was determined as a risk factor for coagulopathy after donor hepatectomy
      on multiple logistic regression analysis. CONCLUSION: The results of this study
      showed that the most important risk factors affecting coagulopathy after donor
      hepatectomy were the parameters associated with remnant liver volume.

PMID- 28740954
TI  - Can red cell distribution width be used as a predictor of acute cholecystitis?
AB  - OBJECTIVE: Acute cholecystitis is a common disease requiring accurate markers for
      diagnosis and proper treatment. The aim of this study was to investigate the role
      of red cell distribution width (RDW) in acute cholecystitis. MATERIAL AND
      METHODS: 299 were included in the study. The subjects were divided into 2 groups;
      group 1 (n: 46) acute cholecystitis group and group 2 (n: 253) chronic
      cholecystitis group. The patients were compared with respect to demographic
      characteristics, white blood cell count, C-reactive protein, and red cell
      distribution width. RESULTS: A statistically significant difference was observed
      between groups with respect to gender, white blood cell count, C-reactive
      protein, and red cell distribution width level (p<0.05). The mean red cell
      distribution width level of group 1 and 2 was 14.19+/-2.02% and 15.03+/-2.51%,
      respectively. CONCLUSION: Red cell distribution width level can be used as a
      predictor of acute cholecystitis. Multicenter prospective studies should be
      performed to elucidate the exact role of RDW level in acute cholecystitis.

PMID- 28740955
TI  - Outcomes of early cholecystectomy (within 7 days of admission) for acute
      cholecystitis according to diagnosis and severity grading by Tokyo 2013
      Guideline.
AB  - OBJECTIVE: The timing of early cholecystectomy in acute cholecystitis is still
      controversial, and data regarding the use of Tokyo 2013 guideline for diagnosis
      and severity grading in Acute Cholecystitis is limited. The aim of this study was
      to evaluate the clinical and pathologic outcomes of early cholecystectomy after
      72 hr and within seven days of index admission according to Tokyo 2013 guideline
      for diagnosis and severity grading of Acute cholecystitis (in patients with Acute
      cholecystitis. MATERIAL AND METHODS: Medical charts of 172 patients who underwent
      early cholecystectomy after 72 hr and within 7 days of index admission with a
      diagnosis of Acute cholecystitis between Aug 2009 and Apr 2014 were
      retrospectively analyzed. Patients were classified according Tokyo 2013 guideline
      criteria. RESULTS: The median age of the study group was 52 yr. The rates of open
      and laparoscopic cholecystectomies was 53.5% and 33.1%, respectively. Conversion
      to open cholecystectomy was performed in 19 patients (13.4 %). The median length
      of hospital stay was 7 days. Eighty-four patients (59.2%) met the criteria for a
      definite diagnosis of Acute cholecystitis according to Tokyo 2013 guideline.
      Longer postoperative and total length of hospital stay was determined in patients
      with a definite diagnosis. CONCLUSION: Increased severity grading is correlated
      with longer pre- and post-operative hospital stay. Early cholecystectomy in Acute
      cholecystitis performed by experienced surgeons after 72 hr of admission and
      within 7 days maybe a feasible and safe procedure.

PMID- 28740956
TI  - Publication rates of abstracts presented at the annual congress of the Turkish
      Society of Colorectal Surgery (years 2003-2011).
AB  - OBJECTIVE: The aim of our study is to examine the Publication Rate of Congress of
      Turkish Society of Colorectal Surgery meeting abstracts and determine the factors
      affecting publication rate. MATERIAL AND METHODS: All presentations at Congress
      of Turkish Society of Colorectal Surgery congresses held in 2003, 2007, 2009,
      2011 were retrospectively assessed. Manuscripts indexed in Google-Scholar
      database were included. The meeting year, study type, presentation type, title
      and time to publication of studies were assessed. Actual impact factor values
      were assessed to introduce the scientific power of the journals. RESULTS: Among a
      total of 614 abstracts presented at these congresses, 139 (22.6%) presentations
      were published in various medical journals. The publication rate was higher in
      oral presentations as group compared to poster presentations (29.7% vs. 19.5%)
      (p<0.001). Mean time to publication period was 20.4 (+/-21.1) months. 78 (56.1%)
      of published articles were published in SCI-E journals while 61 (43.9%) were
      published in non-SCI-E journals. Experimental studies had a higher Publication
      Rate in analysis of publication rate according to study type (p<0.001).
      Prospective clinical studies had a higher publication rate than retrospective
      studies. The journals in which oral presentations had been published had greater
      impact factor than journals in which poster presentations had been published
      (p=0.02). If published; prospective clinical studies were published in journals
      with greater impact factor than retrospective studies (p=0.04). CONCLUSION: The
      quality of a meeting is correlated with the publication of abstracts accepted as
      presentations. Congress of Turkish Society of Colorectal Surgery congress is an
      efficient meeting for researchers, and have a lower PR as compared to
      international congresses while having a similar publication rate to equivalent
      scientific meetings. Being more selective during abstract acceptance should
      increase the Publication Rate and quality of Congress of Turkish Society of
      Colorectal Surgery congresses.

PMID- 28740957
TI  - Xenotransplantation of human cryopreserved parathyroid tissue isolated from
      parathyroid adenomas to normocalcemic rabbits.
AB  - OBJECTIVE: Parathyroid allotransplantation is a new method for the treatment of
      permanent hypoparathyrodism. Adenoma cells are not used for transplantation
      because of the potential for functional or histopathologic transformation. In
      this study, we transplanted human adenomatous parathyroid cells to rabbits.
      MATERIAL AND METHODS: Parathyroid adenoma tissue taken from a male patient was
      cryopreserved and transplanted into seven New Zealand white rabbits (mean weight,
      3700+/-220 g; mean age, 4.5 months) under immunosuppression. The levels of
      parathormone, calcium and phosphorus were measured before and after
      transplantation, and the parathyroid cells were observed histopathologically.
      RESULTS: Mean parathyroid hormone level was 0.5 pg/dL before transplantation and
      6.6 pg/dL after transplantation (p<0.05). Preoperative mean calciumlevel was 14.1
      mg/dL, and mean phosporus level was 3.5 mg/dL before transplantation while these
      values were 14.4 mg/dL and 3.3 mg/dL, respectively, after transplantation
      (p>0.05). Morphologic transformation was not observed in parathyroid cells after
      transplantation. CONCLUSION: In short-term observation, adenomatous parathyroid
      cells can function without malignant transformation. In the future, the
      preliminary methodology in this study may serve as a safe alternative for
      allotransplantation into patients with permanent hypoparathyroidism.

PMID- 28740958
TI  - The outcomes of intestinal resection during debulking surgery for ovarian cancer.
AB  - OBJECTIVE: To evaluate the clinical and surgical outcomes of intestinal resection
      during primary debulking surgery for ovarian cancer. MATERIAL AND METHODS: This
      retrospective study was conducted at Zekai Tahir Burak Women's Health Training
      and Research Hospital between 2009 and 2013. The patients who underwent
      intestinal resection during debulking surgery for stage 3 ovarian cancer were
      included in the analysis. Data regarding patient age, body mass index, tumor
      histology, disease stage, the site of intestinal resection, all postoperative
      complications, duration of intensive care unit admission and hospital stay were
      collected and analyzed. RESULTS: A total of 22 patients with a mean age of 53.4
      years were included in the study. Optimal cytoreduction was achieved in 14 (63%)
      patients. Transverse colectomy was the most common type of intestinal resection
      (63%). The most common postoperative complication was transfusion of blood
      products (63%). No postoperative mortality was observed. CONCLUSION: Intestinal
      resection is a crucial part of debulking surgery for advanced ovarian cancer,
      with acceptable complication rates. Despite the limited number of patients, the
      results obtained from the present study are comparable with previous reports.

PMID- 28740959
TI  - Idiopathic granulomatous mastitis: an institutional experience.
AB  - OBJECTIVE: To study idiopathic granulomatous mastitis with respect to its various
      clinical features, etiologic factors, treatment modalities and complications.
      MATERIAL AND METHODS: Retrospective study of all patients who were diagnosed with
      idiopathic granulomatous mastitis from 1st January 2006 to 31st December 2014 at
      Kasturba Hospital, Manipal, India (a tertiary care referral centre). The research
      was performed according to the World Medical Association Declaration of Helsinki.
      Informed consent was taken from the patient before invasive procedures including
      surgery. Data was analysed using the Statistical Package for Social Sciences
      version 16.0 wherever appropriate. RESULTS: 73 patients diagnosed with idiopathic
      granulomatous mastitis during the time period were included. One patient was a
      male (1.37%), rest were all females (98.63%). The mean age of presentation was
      32.67 years (range 23 to 66 years). 70 patients (95.89%) were parous females.
      Average duration since last childbirth was 4.6 years (range: 3 months to 33
      years). 8 patients (10.95%) were lactating. History of oral contraceptive pill
      use was present in 40 patients (54.79%). The right breast was affected in 44
      patients (60.27%), and the left breast in 29 patients (39.73%). None of the
      patients had bilateral disease. The most common symptom was a painless lump
      (61.64%). Rest of the patients (38.36%) presented with features of a breast
      abscess. 19 out of 39 FNACs done (48.72%) were positive for granulomatous
      mastitis. 59 were primarily managed surgically (lumpectomy/wide excision-33,
      incision & drainage-26). One patient was treated primarily with prednisolone. 13
      patients did not receive specific treatment, and were only kept on regular follow
      up. Patients managed with lumpectomy/wide excision had the least rate of
      complications & recurrence (18.18%). CONCLUSION: Patients with idiopathic
      granulomatous mastitis can present with a wide variety of symptoms which mimic
      other more common conditions. Surgical management in the form of wide excision
      appears to provide the best long term outcome in patients with idiopathic
      granulomatous mastitis.

PMID- 28740960
TI  - Prognostic factors in patients with acute mesenteric ischemia.
AB  - OBJECTIVE: Acute mesenteric ischemia, one of the causes of acute abdominal pain
      due to occlusion of the superior mesenteric artery, has a fatal course as a
      result of intestinal necrosis. There is no specific laboratory test to diagnose
      acute mesenteric ischemia. The basis of treatment in cases of acute mesenteric
      ischemia is composed of early diagnosis, resection of intestinal sections with
      infarction, regulation of intestinal blood flow, second look laparotomy when
      required, and intensive care support. The aim of this study is to investigate the
      factors affecting mortality in patients treated and followed-up with a diagnosis
      of acute mesenteric ischemia. MATERIAL AND METHODS: Forty-six patients treated
      and followed-up with a diagnosis of acute mesenteric ischemia between January
      1st, 2008 and December 31st, 2014 at the General Surgery Clinic of our
      hospitalwere retrospectively evaluated. The patients were grouped as survivor
      (Group 1) and dead (Group 2). Age, gender, accompanying disorders, clinical,
      laboratory and radiologic findings, duration until laparotomy, evaluation
      according to the Mannheim Peritonitis Index postoperative complications, surgical
      treatment applied, and type of ischemia and outcome following surgery were
      recorded. RESULTS: A total of 46 patients composed of 22 males and 24 females
      with a mean age of 67.5+/-17.9 and with a diagnosis of mesenteric ischemia were
      included in the study. Twenty-seven patients died (58.7%) while 19 survived
      (41.3%). The mean MPI score was 16.8+/-4.7 and 25.0+/-6 in Group 1 and Group 2,
      respectively, and the difference between the two groups was statistically
      significant (p<0,001). Fourteen of the 16 (51.9%) patients who had a Mannheim
      Peritonitis Index score of 26 or higher died while two of them survived (10.5%).
      Thirteen out of the 30 (48.1%) patients with a Mannheim Peritonitis Index score
      of 25 or lower died while 17 (89.5%) patients survived. The increased MPI score
      was significantly correlated withmortality (p=0.004). CONCLUSION: Suspicion of
      disease and early use of imaging in addition to clinical and laboratory
      evaluations are essential in order to decrease mortality rates in acute
      mesenteric ischemia. Prevention of complications with critical intensive care
      during the postoperative period aids in decreasingthe mortality rate. In
      addition, using the Mannheim Peritonitis Index can be helpful.

PMID- 28740961
TI  - Isolated thyroid metastasis from renal cell carcinoma.
AB  - Metastatic neoplasms of the thyroid are uncommon when compared to primary tumors
      of the gland. Renal cell carcinoma (RCC) is a highly aggressive tumor of the
      urinary system. It can spread all over the body. Isolated solitary metastases of
      RCC to the thyroid are very rarely observed. A 64-year-old woman with a history
      of left radical nephrectomy for RCC, was referred to our clinic with palpable
      thyroid nodule. Ultrasound confirmed the nodule on the left lobe.
      Histopathological examination of the thyroidectomy specimen revealed that there
      were two solitary metastasis of RCC. No other distant metastasis were detected.
      Metastatic tumors of the thyroid gland are very rare. When patients with thyroid
      nodule are referred to our clinic with the history of other malignancies, we must
      consider metastasis. Thyroidectomy is recommended in the case of isolated thyroid
      metastasis of RCC.

PMID- 28740962
TI  - The effect of corticosteroid treatment on bilateral idiopathic granulomatous
      mastitis.
AB  - Idiopathic granulomatous mastitis (IGM) is the commonly encountered form of
      granulomatous mastitis that may result into repetitive infections and/or abscess
      formation. Mastitis may develop secondary to a systemic disorder such as
      tuberculosis, diabetes mellitus, or rheumatoid arthritis, or it may develop as an
      idiopathic disorder. Idiopathic granulomatous mastitis is the most frequent form
      of all granulomatous diseases affecting the breast. This disorder frequently
      presents as painful and fast-growing mass in the breast. Biopsy is required to
      confirm diagnosis. Surgical excision and immunosuppressive treatment with
      corticosteroids are employed for therapeutic management. Here we present 3 female
      cases of bilateral IGM who were followed up and treated successfully with 1
      mg/kg/day prednisolone.

PMID- 28740963
TI  - Extra-adrenal myelolipoma with hemolytic anemia.
AB  - Myelolipomas are rare benign tumors often detected as adrenal masses. Extra
      adrenal myelolipomas are encountered even more rarely. The rate of detection of
      these lesions is increasing with improved radiological techniques. Because of
      their localization and morphological similarities to well differentiated
      liposarcomas, extra-adrenal myelolipomas need to be differentiated from other
      aggressive neoplasms. Preoperative imaging and percutaneous biopsy are important
      tools in the diagnosis of these lesions. We report a very rare case of an extra
      adrenal perirenal myelolipoma associated with hemolytic anemia. The etiology,
      differential diagnosis, and treatment options for the lesion have been discussed.
      Fat-containing tumors of the retroperitoneum should be considered in the
      differential diagnosis. Accurate diagnosis is important to avoid over-treatment
      of these benign lesions.

PMID- 28740964
TI  - Isolated chylous injury due to blunt abdominal trauma: Report of a case and a
      review of the literature.
AB  - The chyle duct (CD) lies close to the spine behind the right renal vein and vena
      cava. Forces capable of tearing the CD may also injure other adjacent structures
      or organs. Cases of isolated chylous injury are rarely reported in the
      literature. Our aim was to report a case of isolated chylous injury due to blunt
      abdominal trauma that was successfully treated non-operatively. A 54-year-old man
      was involved in a deceleration-type traffic accident. His physical examinations,
      radiologic evaluations, paracentesis, and laboratory findings revealed isolated
      chylous injury resulting from intra- and retroperitoneal chylous fluid
      collection. The patient was treated via percutaneous drainage and medical
      therapy. This condition is generally self-limited and resolves without the
      necessity of any surgical interventions. However, if medical treatment is
      unsuccessful, the decision of diagnostic laparoscopy or exploratory laparotomy
      becomes inevitable.

PMID- 28740965
TI  - A rare cause of acute abdomen: Chylous ascites.
AB  - Chylous ascites, defined as a lipid-rich fluid accumulation in the peritoneal
      cavity, is a rare pathology of the lymphatic system and is a very rare cause of
      acute abdomen. It is generally associated with diseases such as cancer,
      cirrhosis, inflammatory diseases, surgery, or trauma. In this study, we report a
      patient with chylous ascites, which mimics acute appendicitis. Diagnosis and
      treatment procedures were discussed.

PMID- 28740966
TI  - Portal vein thrombosis as a rare cause of abdominal pain: When to consider?
AB  - Extrahepatic portal vein thrombosis (PVT) is a rare condition that is
      characterized by the presence of thrombus within any segment of the portal vein,
      including the right and left intrahepatic branches. It may also extend to the
      splenic or superior mesenteric veins. Portal vein thrombosis may be related to
      cirrhosis or liver malignancy as well as to local inflammatory conditions in the
      abdomen and genetic or acquired thrombophilic diseases. Currently, PVT is being
      increasingly diagnosed due to advances in modern imaging techniques. The clinical
      presentation has a wide range, from an asymptomatic lesion to a potentially life
      threatening situation. In this study, we present three patients with PVT. The
      diagnosis was made by radiologic and clinical findings. In the first patient,
      genetic testing revealed factor V Leiden mutation as the cause of PVT. The second
      patient was diagnosed with lupus anticoagulant syndrome as the cause of PVT.
      Portal vein thrombosis was associated with intra abdominal infection due to
      anastomotic leakage in the third patient. Two patients were successfully treated
      with anticoagulant therapy. This report emphasizes that even though PVT is a rare
      cause of abdominal pain, timely diagnosis and appropriate management is vital due
      to its lethal complications such as mesenteric ischemia and mesenteric infarct.

PMID- 28740967
TI  - Incidental gastrointestinal stromal tumor at a gastroscopic polypectomy specimen:
      A case report and review of literature.
AB  - Although gastrointestinal stromal tumors (GISTs) comprise less than 1% of all
      gastrointestinal (GI) tract tumors, they are the most common mesenchymal tumors
      of the GI tract. Gastrointestinal stromal tumors can occur anywhere along the GI
      tract, but the stomach and small intestine are the most frequently involved
      sites. Gastrointestinal stromal tumors are frequently asymptomatic, and one-third
      of all cases are found incidentally. Endoscopy, endoscopic ultrasonography, and
      computed tomography are useful tools in the diagnosis. Endoscopic mucosal
      resection, endoscopic submucosal dissection, laparoscopic endoscopic cooperative
      surgery, and surgery with either laparoscopic or open approaches are treatment
      modalities for GISTs. An R0 resection is the principle surgery. Imatinib is the
      main medical agent used in the adjuvant or neoadjuvant treatment of GIST. We
      present a 65-year-old woman with an asymptomatic GIST that arose from a gastric
      polyp treated via endoscopic polypectomy.

PMID- 28740968
TI  - Epidermal cyst mimicking incision line metastasis.
AB  - Epidermal cysts are cystic tumors lined with keratinized squamous layer and
      filled with keratin debris. Epidermal cysts may develop by implantation of
      surface epidermal layer into the dermis or subcutaneous tissue after trauma or
      surgical procedures. Cervix cancer spreads either directly or via the vascular
      and lymphatic systems. Distant skin metastasis of endometrium or cervix cancer is
      very rare. In this case report, a patient who had a history of cervix cancer
      operation 11 years ago and presented with a mass that mimicked incision line
      metastasis and was histopathologically diagnosed with epidermal cyst is
      presented.

PMID- 28740969
TI  - An in-vitro study comparing the accuracy of ?full-arch casts digitized with
      desktop scanners.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of full-arch
      scans using 11 different cast scanners. METHOD AND MATERIALS: Dental arch length
      (AL), intermolar width (IMW), and intercanine width (ICW) of the reference
      plaster casts were measured using a coordinate measuring machine (Zeiss O-Inspect
      422). The master cast was subsequently scanned 37 times using 11 desktop scanners
      (3Shape R500, 3Shape R700, 3Shape R1000, 3Shape R2000, Medianetx grande,
      Medianetx colori, DentaCore CS ULTRA, Dentaurum OrthoX, Maestro 3D, Imetric IScan
      D104i, GC Aadva Lab Scan). Using the software Convince Premium 2012 (3Shape), AL,
      IMW, and ICW were measured on the digital models and compared to the reference
      plaster cast. RESULTS: The accuracy of the cast scanners differed significantly.
      The most accurate measurements were given by the cast scanners 3Shape R700 (ICW:
      7.4?+/-?5.9?um) and Imetric IScan D104i (ICW: 9.1?+/-?4.9?um). The cast scanners
      3Shape R1000 (ICW: 11.2?+/-?3.4?um) and GC Aadva Lab Scan (ICW: 13.8?+/-?8.1?um)
      yielded comparable measurements. DentaCore (ICW: 26.6?+/-?7.5?um) and Dentaurum
      OrthoX (ICW: 31.1?+/-?24?um) were significantly less accurate. CONCLUSION: Almost
      all scanners demonstrated a level of accuracy so high that further improvement
      would not provide additional benefit for use in orthodontics. Advancement of the
      scanners should focus primarily on reducing time and cost. For prosthodontic use,
      the scanners with the highest accuracy are recommended.

PMID- 28740970
TI  - Anterior mandibular rehabilitation causing chronic obstructive sialadenitis: ?A
      series of sialo-CBCT cases and literature review.
AB  - OBJECTIVE: The aim of this study was to assess and present, using sialo-cone beam
      computed tomography (sialo-CBCT) examination, cases of submandibular gland (SM)
      chronic obstructive sialadenitis (COS) caused by dental rehabilitation. DATA
      SOURCES: Clinical and radiographic data of all patients referred for SM sialo
      CBCT imaging in the Oral and Maxillofacial Imaging Unit with recurrent SM
      swelling between January 2012 and July 2015 were reviewed. Cases with suggested
      iatrogenic cause were selected and described. A literature review of similar
      cases was also performed. RESULTS: Seventy-one patients with salivary gland (SG)
      swelling were referred for SM sialo-CBCT. Of these, 16 had implant-supported
      fixed partial prostheses and seven had full mandibular overdentures. In five
      patients, COS was diagnosed and a causal relationship between their dental
      rehabilitation and symptoms was suggested. A literature search revealed 11 cases
      of SM COS secondary to anterior mandibular rehabilitation. CONCLUSION: Clinicians
      rehabilitating the anterior edentulous mandibular region should be aware that
      both fixed and removable devices may block the orifices of the SM, causing COS.

PMID- 28740971
TI  - Monolithic lithium disilicate complete single crowns with feather-edge
      preparation design in the posterior region: A multicentric retrospective study up
      to 12 years.
AB  - OBJECTIVE: This retrospective study evaluated the clinical success and survival
      of monolithic lithium disilicate single crowns in the posterior region fabricated
      with feather-edge margins and cemented with resin-based self-etching cement.
      METHOD AND MATERIALS: In total, 627 pressed monolithic lithium disilicate
      restorations on posterior teeth (110 first premolars, 151 second premolars, 240
      first molars, 121 second molars, 5 third molars) were placed in 335 patients. All
      teeth were prepared with feather-edge margins and restored with single crowns.
      The modified California Dental Association criteria were used to clinically
      evaluate subjects during regular maintenance recalls. RESULTS: The mean follow-up
      time was 48.17 months (SD, 27.7; range, 6 to 144). Nine crowns were replaced
      during the follow-up period due to bulk fracture of the material (overall 97.93%
      survival rate), and four teeth were extracted. No other technical or biologic
      failure was observed. CONCLUSION: In this retrospective evaluation, monolithic
      lithium disilicate crowns with feather-edge margins yielded clinical outcomes
      similar to those reported with other margin designs and materials. Following the
      same clinical protocol, crowns on second molars showed lower survival rates when
      compared to restorations on other teeth in the posterior region. Careful
      evaluation is mandatory in high-risk patients and terminal teeth. Alternative
      restorative materials, such as full-contour zirconia crowns, should be considered
      for the restoration of second molars.

PMID- 28740972
TI  - In-vivo microbiologic evaluation of polytetrafluoroethylene and cotton as
      endodontic spacer materials.
AB  - OBJECTIVE: Spacers are commonly placed between the canal orifice and the
      temporary material between endodontic treatment appointments. This prevents the
      temporary restoration material from obstructing the canal orifices and allows for
      easy removal. Various endodontic spacers are currently used, including
      polytetrafluoroethylene (PTFE) tape. Previous in-vitro studies have demonstrated
      the advantages of using PTFE over using cotton; however, no in-vivo studies have
      demonstrated this. Hence, the purpose of this study was to evaluate which spacer
      showed less bacterial leakage between endodontic treatments. METHOD AND
      MATERIALS: Fifty patients participated in the study and were randomly assigned to
      either the cotton or the PTFE group. Root canal treatments were completed in two
      appointments. Cotton and PTFE spacers were collected after a 2- to 4- week time
      interval between the first and second appointments. Samples were incubated on
      agar plates for 48 hours and then evaluated for presence of microbial growth.
      Colony forming units (CFUs) were counted for each of the samples. The results
      were analyzed using nonparametric statistical tests. RESULTS: Fifteen of the 24
      cotton spacers and two of the 24 PTFE spacers were positive for bacterial growth.
      CONCLUSION: Cotton fibers exposed to the oral environment could potentially wick
      contaminants into the pulp chamber. The tendency of cotton to distort under
      masticatory forces may allow disruption of the temporary material's marginal
      seal. Based on the results of this study, the use of PTFE is strongly recommended
      over cotton as an endodontic spacer material. PTFE performed better than cotton
      in this in-vivo microbial study.

PMID- 28740973
TI  - Prosthodontic treatment of an Angle III Class malocclusion: A case report.
AB  - Patients with an Angle Class III malocclusion are generally treated by
      orthodontics with or without orthognathic surgery. A literature search revealed
      very few articles describing solely the prosthodontic treatment of a Class III
      malocclusion, as it is rarely used as a treatment modality in these cases. The
      purpose of this article is to show the effects and benefits of an increase in the
      vertical dimension of the occlusion (VDO) in patients with a Class III
      malocclusion. An increase in the VDO causes a clockwise rotation of the mandible,
      thereby increasing the reverse overjet. This phenomenon allows a prosthodontic
      treatment of the Class III malocclusion in some patients. Therefore, proper
      diagnostic procedures, careful planning, and a simulation of the final appearance
      by wax-up and mock-up are mandatory when choosing the modality of prosthodontic
      treatment. A case with a Class III malocclusion, treated solely by prosthodontic
      means, is presented. The implemented prosthodontic treatment included the
      correction of the crossbite and the occlusal plane, the reestablishment of the
      anterior and canine guidance as well as the provision of a stable occlusion and
      enhanced facial and dental esthetics. It is proposed that an increase of the VDO
      should be taken into consideration whenever a patient with a Class III
      malocclusion is prosthodontically treated.

PMID- 28740974
TI  - Wound closure and wound healing. Suture techniques in contemporary periodontal
      and implant surgery: Interactions, requirements, and practical considerations.
AB  - In contemporary reconstructive periodontal and implant surgery, attaining
      uncomplicated wound healing in the early postoperative healing phase is the key
      to achieving a successful treatment outcome and is of central interest, from the
      clinical as well as the scientific perspective. The realization of primary wound
      healing is the central challenge in most cases. Two of the evidence-based factors
      that affect postoperative wound healing can be influenced by the surgeon: the
      blood supply to the surgical site and postoperative wound stability. The surgical
      suture is a key determinant of whether adequate wound stability is achieved in
      this context without complicating the course of wound healing by exerting
      unnecessary trauma or excessive tensile strain on the wound edges. Therefore, the
      inclusion of anchors in the suturing process that make it possible to achieve the
      best wound stability possible is often an important key to success. This article
      provides an overview of the principles of successful wound closure that are
      relevant to postoperative wound healing in order to equip dentists with the tools
      needed for the correct, indication-specific selection and performance of surgical
      suturing techniques in daily practice.

PMID- 28740975
TI  - Tyrosol and its metabolites as antioxidative and anti-inflammatory molecules in
      human endothelial cells.
AB  - Tyrosol (Tyr) is a phenolic compound found in virgin olive oil. After ingestion,
      Tyr undergoes extensive first pass intestinal/hepatic metabolism. However,
      knowledge about the biological effects of Tyr metabolites is scarce. We
      chemically synthesized Tyr glucuronate (Tyr-GLU) and sulphate (Tyr-SUL)
      metabolites and explored their properties against oxidative stress and
      inflammation in TNF-alpha-treated human umbilical vein endothelial cells (hECs).
      Tyr and Tyr-SUL prevented the rise of reactive oxygen species, the depletion of
      glutathione, and the down-regulation of glutathione peroxidase 1, glutamate
      cysteine ligase catalytic subunit, and heme oxygenase-1 genes. Tyr-SUL and to a
      lower extent Tyr and Tyr-GLU prevented the phosphorylation of NF-kappaB signaling
      proteins. Tyr-GLU and Tyr-SUL also prevented the over-expression of adhesion
      molecules at gene, protein, and secretory levels, and the adhesion (Tyr-SUL > Tyr
      GLU) of human monocytes to hECs. In vivo, Tyr, and most notably Tyr-SUL in a dose
      dependent manner, ameliorated plantar and ear edemas in mice models of acute and
      chronic inflammation. This study demonstrates the antioxidant and/or anti
      inflammatory properties of Tyr metabolites, with Tyr-SUL being the most
      effective.

PMID- 28740976
TI  - A kinetic study of the CH2OO Criegee intermediate reaction with SO2, (H2O)2,
      CH2I2 and I atoms using OH laser induced fluorescence.
AB  - The OH laser induced fluorescence method was used to study the kinetics of CH2OO
      reacting with SO2, (H2O)2, CH2I2 and I atoms. Decay of CH2OO is not strictly
      first-order since its self-reaction is rapid. With this consideration, we derived
      the rate coefficient of CH2OO + SO2/(H2O)2/CH2I2/I taking into account the
      contribution of the CH2OO self-reaction. For the CH2OO + SO2 reaction, the rate
      coefficient is measured to be (3.88 +/- 0.13) * 10-11 cm3 molecule-1 s-1 at 10
      Torr, which agrees very well with a previously reported value obtained by
      directly monitoring CH2OO using the UV absorption method with the CH2OO self
      reaction considered. We did not observe obvious evidence for SO2 catalysed CH2OO
      isomerization or the intersystem crossing effect in this reaction. CH2OO + (H2O)2
      is supposed to account for the major sink of CH2OO in the atmosphere, but
      previous rate coefficient measurements were not in good agreement. We have
      revisited this reaction including the self-reaction of CH2OO and obtained the
      rate coefficient to be (7.53 +/- 0.38) * 10-12 cm3 molecule-1 s-1 at 60 Torr and
      300 K. The rate coefficients of CH2OO + CH2I2 and CH2OO + I were measured to be
      (5.2 +/- 2.6) * 10-14 and (2.2 +/- 1.1) * 10-12 cm3 molecule-1 s-1 respectively.

PMID- 28740977
TI  - Effects of addition of hydrocolloids on the textural and structural properties of
      high-protein intermediate moisture food model systems containing sodium
      caseinate.
AB  - High-protein intermediate moisture food (HPIMF) containing sodium caseinate
      (NaCN) often gave a harder texture compared with that made from whey proteins or
      soy proteins, due to the aggregation of protein particles. The objectives of this
      study were to explore whether the addition of hydrocolloids could soften the
      texture and illustrate the possible mechanism. Three kinds of hydrocolloids,
      xanthan gum, kappa-carrageenan, and gum arabic were chosen, and samples including
      of these three kinds of hydrocolloids were studied through texture analysis using
      a TPA test and microstructure observation by confocal laser scanning microscopy
      (CLSM) and scanning electron microscopy (SEM). The texture analysis results
      showed that xanthan gum was more effective at softening the HPIMF containing NaCN
      compared to kappa-carrageenan and gum arabic. In addition, with the increase of
      xanthan gum concentration from 0.2 to 2%, the HPIMF matrix became softer, and
      fractures were observed during the compression for samples with xanthan gum added
      at low concentrations but not 2%. Microstructure observation suggested that the
      matrix originally dominated by the network formed through the aggregation of
      swollen protein particles was inhibited by the addition of xanthan gum, resulting
      in the softening of the texture and also contributing to the fracture during
      compression. With the increase of xanthan gum concentration up to 2%, the protein
      dominating network would be gradually replaced with a matrix dominated by the
      newly formed network of xanthan gum with protein particles as fillers.
      Furthermore, this formation of a xanthan gum dominating network structure also
      resulted in changes in small molecule distribution, as observed using low-field
      NMR.

PMID- 28740978
TI  - Synthesis and photo-/electro-catalytic properties of a 3D POMOF material based on
      an interpenetrated copper coordination polymer linked by in situ dual ligands and
      Dawson-type phosphotungstates.
AB  - A novel 3D polyoxometalate metal organic framework (POMOF), [{CuCu
      (H2O)5(pzc)10(pz)6}{P2W18O62}2].4H2O (1) (Hpzc = pyrazine-2-carboxylic acid, pz =
      pyrazine) has been hydrothermally synthesized and characterized by IR, TG, XRD,
      UV-vis and elemental analyses. In compound 1, the pzc and pz ligands are
      generated through in situ transformation from pyrazine-2,3-dicarboxylic acid
      (pzdc) to remove one or two CO2 molecules. The ligands with four coordination
      modes connect nine crystallographically independent Cu atoms to form a super-big
      circle unit. Each ring unit is connected to the adjacent six rings via an edge
      sharing way to form a 2-D Cu/pz/pzc MOF layer, which is further extended along
      two spatial directions by two kinds of insert modes to generate an
      interpenetrating and staggered 3-D metal organic network. The {P2W18} clusters as
      nine-node inorganic guest molecules are grafted on the Cu/pz/pzc framework
      forming a complex 3D POMOF with a new topology {4.6.83.10}2 {4.6.8}2
      {4.62.82.10}2{4.63.82}2{4.85}2{42.62.82}2{42.63.8}{43.67.813.1010.123}2
      {4}6{6.82}2{62.8}2 {64.8.10}{6}2{8}4. Additionally, compound 1 exhibits good
      electrocatalytic activity for the reduction of H2O2 and effective photocatalytic
      degradation ability for three azo dyes under UV irradiation.

PMID- 28740979
TI  - Transport of water molecules through noncylindrical pores in multilayer
      nanoporous graphene.
AB  - In this study, molecular dynamics (MD) simulations are used to examine the water
      transport properties through asymmetric hourglass-shaped pores in multilayer
      nanoporous graphene with a constant interlayer separation of 6 A. The properties
      of the tested asymmetric hourglass-shaped pores [with the models having long cone
      (l1, -P) and short cone (l2, +P) entrances] are compared to a symmetric pore
      model. The study findings indicate that the water occupancy increases across the
      asymmetric pore (l1, -P) compared to (l2, +P), because of the length effect. The
      asymmetric pore, (l1, -P), yields higher flux compared to (l2, +P) and even the
      symmetric model, which can be attributed to the increase in the hydrogen bonds.
      In addition, the single-file water molecules across the narrowest pore diameter
      inside the (l2, +P) pore exhibit higher viscosity compared to those in the (l1, 
      P) pore because of the increase in the water layering effect. Moreover, it is
      found that the permeability inside the multilayer hourglass-shaped pore depends
      on the length of the flow path of the water molecules before approaching the
      layer with the smallest pore diameter. The probability of dipole orientation
      exhibits wider distribution inside the (l1, -P) system compared to (l2, +P),
      implying an enhanced formation of hydrogen bonding of water molecules. This
      results in the fast flow of water molecules. The MD trajectory shows that the
      dipole orientation across the single-layer graphene has frequently flipped
      compared to the dipole orientation across the pores in multilayer graphene, which
      is maintained during the whole simulation time (although the dipole orientation
      has flipped for a few picoseconds at the beginning of the simulation). This can
      be attributed to the energy barrier induced by the individual layer. The
      diffusion coefficient of water molecules inside the (l2, +P) system increases
      with pressure difference, however, it decreases inside the (l1, -P) system
      because of the increase in the number of collisions. It was found that the
      velocity in the axial direction (z-direction) has a significant impact on the
      permeation ability of water molecules across the asymmetric nanopores examined in
      this study. Finally, the study results suggest that the appropriate design of an
      asymmetric hourglass-shaped nanopore in multilayer graphene can significantly
      improve the water permeation rate even compared to a symmetric structure.

PMID- 28740980
TI  - Micro-engineered perfusable 3D vasculatures for cardiovascular diseases.
AB  - Vessel geometries in microengineered in vitro vascular models are important to
      recapitulate a pathophysiological microenvironment for the study of flow-induced
      endothelial dysfunction and inflammation in cardiovascular diseases. Herein, we
      present a simple and novel extracellular matrix (ECM) hydrogel patterning method
      to create perfusable vascularized microchannels of different geometries based on
      the concept of capillary burst valve (CBV). No surface modification is necessary
      and the method is suitable for different ECM types including collagen, matrigel
      and fibrin. We first created collagen-patterned, endothelialized microchannels to
      study barrier permeability and neutrophil transendothelial migration, followed by
      the development of a biomimetic 3D endothelial-smooth muscle cell (EC-SMC)
      vascular model. We observed a significant decrease in barrier permeability in the
      co-culture model during inflammation, which indicates the importance of
      perivascular cells in ECM remodeling. Finally, we engineered collagen-patterned
      constricted vascular microchannels to mimic stenosis in atherosclerosis. Whole
      blood was perfused (1-10 dyne cm-2) into the microdevices and distinct platelet
      and leukocyte adherence patterns were observed due to increased shear stresses at
      the constriction, and an additional convective flow through the collagen. Taken
      together, the developed hydrogel patterning technique enables the formation of
      unique pathophysiological architectures in organ-on-chip microsystems for real
      time study of hemodynamics and cellular interactions in cardiovascular diseases.

PMID- 28740981
TI  - The adsorption and diffusion behavior of noble metal adatoms (Pd, Pt, Cu, Ag and
      Au) on a MoS2 monolayer: a first-principles study.
AB  - First-principles calculations based on periodic density functional theory (DFT)
      have been used to investigate the geometries, electronic structures, magnetic
      properties and diffusion behaviors of different noble metal adatoms (Pd, Pt, Cu,
      Ag and Au) on MoS2 monolayers. The results demonstrate that these adatoms can
      chemically adsorb on MoS2 monolayers. The band gaps of MoS2 monolayers with a Pd
      or Pt atom adsorbed are reduced owing to impurity states that emerge
      simultaneously within the gap region of the pristine MoS2 monolayer. The unpaired
      electrons in MoS2 monolayers with a Cu, Ag or Au atom adsorbed are spin
      polarized, resulting in total magnetic moments of 1.0 MUB per supercell, which is
      caused by the strong hybridization between the metal adatoms and surrounding Mo
      or S atoms. Long-range antiferromagnetic (AFM) coupling has been observed between
      group IB metal adatoms. Due to charge transfer between adatoms and the MoS2 host,
      the work functions were modulated upon adsorption of noble metals. In addition,
      the diffusion behaviors of noble metal adatoms on the MoS2 monolayer suggest that
      Cu, Pd and Pt atoms favor the formation of a metal nanotemplate on the MoS2
      monolayer, and Ag and Au are likely to form isolated particles in the initial
      growth stage. These findings may provide useful guidance to extend the potential
      applications of MoS2 in low-dimensional nanoelectronic and spintronic devices.

PMID- 28740982
TI  - Pyranose ring conformations in mono- and oligosaccharides: a combined MD and DFT
      approach.
AB  - Among the descriptors of the molecular structure of carbohydrates, the
      conformation of the pyranose ring is usually the most problematic one to tackle.
      We present the results of a systematic study oriented at determining the ring
      inversion properties of all d-hexopyranoses in the form of monosaccharides, O1
      methylated monosaccharides and homotrisaccharides. Contrary to the existing
      studies, based either on molecular mechanics force fields or on conformational
      search within ab initio potentials, we combine the structural information from
      molecular dynamics simulations performed within the GROMOS 56a6CARBO_R force
      field and use it in a subsequent geometry optimization procedure, performed at
      the DFT level of theory. This two-step procedure allows avoiding errors resulting
      from overestimating the contribution of the hydrogen bond-rich, low-energy
      structures that are not abundant in aqueous solutions. The calculated anomeric
      ratios and the populations of staggered conformers of the hydroxymethyl group are
      in satisfactory agreement with the experimental data. Regarding the ring
      inversion properties, for the first time, we achieved good agreement of the ab
      initio-derived data for all hexopyranoses with the experimentally inferred Angyal
      scheme and with the NMR-inferred populations of ring conformers. The same
      computational methodology allows determination of the influence of
      functionalization (methylation or glycosylation) on the ring-inversion properties
      which includes the influence of the anomeric effect, enhanced upon O1
      functionalization. In general, the correlation between ring-inversion properties
      of unfunctionalized monomers and those of O1-methylated, O1-glycosylated, O4
      glycosylated and O1,O4-diglycosylated monomers is qualitatively (but not
      quantitatively) compatible with that predicted by the classical force fields.

PMID- 28740983
TI  - Combining EPR spectroscopy and X-ray crystallography to elucidate the structure
      and dynamics of conformationally constrained spin labels in T4 lysozyme single
      crystals.
AB  - Electron paramagnetic resonance (EPR) spectroscopy in combination with site
      directed spin labeling is used to investigate the structure and dynamics of
      conformationally constrained spin labels in T4 lysozyme single crystals. Within a
      single crystal, the oriented ensemble of spin bearing moieties results in a
      strong angle dependence of the EPR spectra. A quantitative description of the EPR
      spectra requires the determination of the unit cell orientation with respect to
      the sample tube and the orientation of the spin bearing moieties within the
      crystal lattice. Angle dependent EPR spectra were analyzed by line shape
      simulations using the stochastic Liouville equation approach developed by Freed
      and co-workers and an effective Hamiltonian approach. The gain in spectral
      information obtained from the EPR spectra of single crystalline samples taken at
      different frequencies, namely the X-band and Q-band, allows us to discriminate
      between motional models describing the spectra of isotropic solutions similarly
      well. In addition, it is shown that the angle dependent single crystal spectra
      allow us to identify two spin label rotamers with very similar side chain
      dynamics. These results demonstrate the utility of single crystal EPR
      spectroscopy in combination with spectral line shape simulation techniques to
      extract valuable dynamic information not readily available from the analysis of
      isotropic systems. In addition, it will be shown that the loss of electron
      density in high resolution diffraction experiments at room temperature does not
      allow us to conclude that there is significant structural disorder in the system.

PMID- 28740984
TI  - Combined effects of multi-scale topographical cues on stable cell sheet formation
      and differentiation of mesenchymal stem cells.
AB  - To decipher specific cell responses to diverse and complex in vivo signals, it is
      essential to emulate specific surface chemicals, extra cellular matrix (ECM)
      components and topographical signals through reliable and easily reproducible in
      vitro systems. However, the effect of multiple cues such as micro-hole/pillar
      architectures under a common and easily tunable platform remains unexplored.
      Recently we have demonstrated the positive influence of surface chemical
      modification of polydimethylsiloxane (PDMS) surfaces on directing long-term
      adhesion, viability and potency of hMSCs. In this study, we include biophysical
      signals from diverse surface topographical elements along with biochemical
      influences to develop a holistic understanding of hMSC responses in complex
      tissue-like niches. We report the influence of chemically modified PDMS
      structures encompassing hole-, pillar- and groove-based multi-scale architectures
      on hMSC morphology, adhesion, proliferation and differentiation. The inclusion of
      hole and pillar features resulted in enhanced adhesion and proliferation of
      hMSCs. These effects were more pronounced with the inclusion of grooves, which
      resulted in the highest osteogenic differentiation among other substrates. Our
      study provides an additional basis for the chemical/physical regulation of hMSC
      behavior within controlled biomimetic architectures with an aim to foster
      efficient tissue regeneration strategies.

PMID- 28740985
TI  - Tuning the redox potential of vitamin K3 derivatives by oxidative
      functionalization using a Ag(i)/GO catalyst.
AB  - We propose herein initial results to develop optimum redox mediators by the
      combination of computational simulation and catalytic functionalization of the
      core structure of vitamin K3. We aim to correlate the calculated energy value of
      the LUMO of different vitamin K3 derivatives with their actual redox potential.
      For this, we optimized the catalytic alkylation of 1,4-naphthoquinones with a
      designed Ag(i)/GO catalyst and synthesized a series of molecules.

PMID- 28740986
TI  - Probing covalency in halogen bonds through donor K-edge X-ray absorption
      spectroscopy: polyhalides as coordination complexes.
AB  - The properties of halogen bonds (XBs) in solid-state I2X- and I4X- materials
      (where X = Cl, Br) are explored using donor K-edge X-ray absorption spectroscopy
      (XAS) to experimentally determine the degree of charge transfer in such XB
      interactions. The degree of covalency in these bonds is substantial, even in
      cases where significantly weaker secondary interactions are observed. These data,
      in concert with previous work in this area, suggests that certain halogen bonds
      have covalent contributions to bonding that are similar to, and even exceed,
      those observed in transition metal coordinate bonds. For this reason, we suggest
      that XB interactions of this type be denoted in a similar way to coordination
      bonds (X -> Y) as opposed to using a representation that is the same as for
      significantly less covalent hydrogen bonds (XY).

PMID- 28740987
TI  - Rational synthesis of hierarchical magnetic mesoporous silica microspheres with
      tunable mesochannels for enhanced enzyme immobilization.
AB  - Hierarchical magnetic mesoporous silica microspheres (MMSMs) with a core-shell
      structure have been fabricated through an improved water/oil biphase synthesis
      strategy. We firstly reported that the mesopore size can be readily tuned from
      6.1 to 11.4 nm by the synergistic effect of surfactant concentration and an
      amphiphilic agent, thus holding a bright future in many possible applications.

PMID- 28740988
TI  - Sandwiched gold/PNIPAm/gold microstructures for smart plasmonics application:
      towards the high detection limit and Raman quantitative measurements.
AB  - A smart plasmonic sensor, comprising a layer of a stimuli-responsive polymer
      sandwiched between two gold layers, is reported. As a stimuli-responsive
      material, a monolayer of poly(N-isopropylacrylamide) (PNIPAm) crosslinked
      globules is used. A quasi-periodic structure of the top gold layer facilitates
      efficient excitation and serves as a support for plasmon excitation and
      propagation. The intermediate layer of PNIPAm efficiently entraps targeted
      molecules from solutions. The sensor structure was optimized for efficient light
      focusing in the "active" PNIPAm layer. The optimization was based on the time
      resolved finite-element simulations, which take into account the thickness of
      gold layers, size of PNIPAm globules and Raman excitation wavelength (780 nm).
      The prepared structures were characterized using SEM, AFM, UV-Vis refractometry
      and goniometry. Additional AFM scans were performed in water at two temperatures
      corresponding to the collapsed and swollen PNIPAm states. The Raman measurements
      demonstrate a high detection limit and perfect reproducibility of the Raman
      scattering signal for the prepared sensor. In addition, the use of created SERS
      structures for the detection of relevant molecules in the medical, biological and
      safety fields was demonstrated.

PMID- 28740989
TI  - Concave binding of cationic Li to quadrannulene.
AB  - Binding of Li+ to quadrannulene and its influence on buckybowl functionalization
      are introduced. The concave-trapped Li+ acts as a Lewis acid and the rate of
      Diels-Alder cycloaddition is enhanced 108 times. A sandwiched bowl-Li+-bowl
      structure is stabilized via concave-cation-convex interactions, indicating the
      promoted role of Li+ in buckybowl assembly.

PMID- 28740990
TI  - Anthocyanins inhibit tumor necrosis alpha-induced loss of Caco-2 cell barrier
      integrity.
AB  - An increased permeability of the intestinal barrier is proposed as a major event
      in the pathophysiology of conditions characterized by chronic gut inflammation.
      This study investigated the capacity of pure anthocyanins (AC), and berry and
      rice extracts containing different types and amounts of AC, to inhibit tumor
      necrosis alpha (TNFalpha)-induced permeabilization of Caco-2 cell monolayers.
      Caco-2 cells differentiated into intestinal epithelial cell monolayers were
      incubated in the absence/presence of TNFalpha, with or without the addition of AC
      or AC-rich plant extracts (ACRE). AC and ACRE inhibited TNFalpha-induced loss of
      monolayer permeability as assessed by changes in transepithelial electrical
      resistance (TEER) and paracellular transport of FITC-dextran. In the range of
      concentrations tested (0.25-1 MUM), O-glucosides of cyanidin, and delphinidin,
      but not those of malvidin, peonidin and petunidin protected the monolayer from
      TNFalpha-induced decrease of TEER and increase of FITC-dextran permeability.
      Cyanidin and delphinidin acted by mitigating TNFalpha-triggered activation of
      transcription factor NF-kappaB, and downstream phosphorylation of myosin light
      chain (MLC). The protective actions of the ACRE on TNFalpha-induced TEER increase
      was positively correlated with the sum of cyanidins and delphinidins (r2 = 0.83)
      content in the ACRE. However, no correlation was observed between TEER and ACRE
      total AC, malvidin, or peonidin content. Results support a particular capacity of
      cyanidins and delphinidins in the protection of the intestinal barrier against
      inflammation-induced permeabilization, in part through the inhibition of the NF
      kappaB pathway.

PMID- 28740991
TI  - Diffusion Monte Carlo study of excitons and biexcitons in a mass-asymmetric
      electron-hole bilayer.
AB  - We employed the diffusion Monte Carlo method, under fixed node approximation, to
      investigate the various ground state properties of a mass-asymmetric electron
      hole bilayer system. Particularly, we calculated the ground state energy, the
      condensation fraction c, and the pair correlation function g(r) at density rs = 5
      a.u. for the inter-planer distance d <= 0.5 a.u. Based on the characteristics of
      condensate faction and pair correlation functions, we found the phase transition
      from the excitonic fluid phase to the biexcitonic fluid phase at d = 0.24 a.u. We
      also analytically calculated the critical layer separation dcrit for biexciton
      stability, the value for which was almost double the d = 0.24 a.u.

PMID- 28740992
TI  - Sputtering gold nanoparticles on nanoporous bismuth vanadate for sensitive and
      selective photoelectrochemical aptasensing of thrombin.
AB  - In this communication, we report the first demonstration of an efficient
      photoelectrochemical aptasensor based on sputtering Au nanoparticle-modified
      nanoporous BiVO4 for the excellent sensitive and selective detection of thrombin
      with a low detection limit of 0.5 pM and a large linear range.

PMID- 28740993
TI  - Orthogonal thiol-ene 'click' reactions: a powerful combination for fabrication
      and functionalization of patterned hydrogels.
AB  - A combination of 'orthogonal' thiol-ene 'click' reactions is utilized for
      fabrication and functionalization of micro-patterned hydrogels. A furan-protected
      maleimide-containing parent copolymer is partially activated via the retro Diels
      Alder reaction to obtain an 'orthogonally' functionalizable copolymer, where the
      different functional groups can be exploited for multi-functionalization or
      fabrication of functional hydrogels using combination of the nucleophilic and
      radical thiol-ene reactions.

PMID- 28740994
TI  - Au cluster adsorption on perfect and defective MoS2 monolayers: structural and
      electronic properties.
AB  - The adsorption of Aun (n = 1-4) clusters on perfect and defective MoS2 monolayers
      is studied using density functional theory. For the pristine MoS2 monolayer, our
      results show that the electrons are transferred from the support to the adsorbed
      Au clusters, thus a p-doping effect is achieved in the pristine MoS2 monolayer by
      the Au cluster adsorption, which is in good agreement with the experimental
      findings. The adsorption of Au clusters can introduce mid-gap states, which
      modify the electronic and magnetic properties of the systems. The adsorbates
      containing an odd number of Au atoms can introduce a spin magnetic moment of 1
      MUB into the perfect MoS2 monolayer, while those systems containing an even
      number of Au atoms are spin-unpolarized. Two categories of defects, i.e., a
      single S vacancy and Mo antisite defect with one Mo atom replacing one S atom,
      are considered for the defective monolayer MoS2. Compared with the pristine MoS2
      monolayer, the adsorption energies for Au clusters are significantly increased
      for the MoS2 monolayer with a single S vacancy, and there are more electrons
      transferred from the MoS2 monolayer with an S vacancy to the Au clusters. The mid
      gap states and odd-even oscillation magnetic behavior can also be observed when
      Au clusters are adsorbed on the MoS2 monolayer with an S vacancy. For those
      systems of Au clusters on MoS2 monolayers with Mo antisite defects, the
      adsorption energies as well as the magnitude and the direction of transferred
      charge are similar to those for the MoS2 monolayer with an S vacancy. The spin
      polarizations appear in all systems with Mo antisite defects. Our investigations
      suggest that the electronic and magnetic properties of MoS2 nanosheets can be
      effectively modulated by the adsorption of Au clusters.

PMID- 28740995
TI  - Basic Cardiac Life Support: 2016 Singapore Guidelines.
AB  - Basic Cardiac Life Support (BCLS) or cardiopulmonary resuscitation (CPR) refers
      to the skills required (without use of equipment) in the resuscitation of cardiac
      arrest individuals. On recognising cardiac arrest, chest compressions should be
      initiated. Good quality compressions are with arms extended, elbows locked,
      shoulders directly over the casualty's chest and heel of the palm on the lower
      half of the sternum. The rescuer pushes hard and fast, compressing 4-6 cm deep
      for adults at 100-120 compressions per minute with complete chest recoil. Two
      quick mouth-to-mouth ventilations (each 400-600 mL tidal volume) should be
      delivered after every 30 chest compressions. Chest compression-only CPR is
      recommended for lay rescuers, dispatcher-assisted CPR and those unable or
      unwilling to give ventilations. CPR should be stopped when the casualty wakes up,
      an emergency team takes over casualty care or if an automated external
      defibrillator prompts for analysis of heart rhythm or delivery of shock.

PMID- 28740996
TI  - Resuscitation medicine: a dose or two for everyone.

PMID- 28740997
TI  - Guidelines for Bystander First Aid 2016.
AB  - Cardiac life support is a form of first aid for cardiac emergencies. However,
      research and evidence in this field is lacking compared with other forms of first
      aid. Having identified the common emergencies that are encountered in the
      hospital, based on the available evidence, we have put together what could be an
      evidence-based approach to the first aid management of some of these common
      emergencies, viz. breathlessness, chest pain, allergies, stroke, heat injury,
      poisoning, unconsciousness, seizures, and trauma situations such as bleeding,
      wounds, contusions, head injury, burns and fractures. Educating the public is the
      key to developing a first responder bystander. These guidelines could become the
      basis for training of the public.

PMID- 28740998
TI  - Therapeutic temperature management (TTM): post-resuscitation care for adult
      cardiac arrest, with recommendations from the National TTM Workgroup.
AB  - Therapeutic temperature management (TTM) was strongly recommended by the 2015
      International Liaison Committee on Resuscitation as a component of post
      resuscitation care. It has been known to be effective in improving the survival
      rate and neurologic functional outcome of patients after cardiac arrest. In an
      effort to increase local adoption of TTM as a standard of post-resuscitation
      care, this paper discusses and makes recommendations on the treatment for local
      providers.

PMID- 28740999
TI  - Advanced Cardiac Life Support: 2016 Singapore Guidelines.
AB  - The main areas of emphasis in the Advanced Cardiac Life Support (ACLS) guidelines
      are: early recognition of cardiac arrest and call for help; good-quality chest
      compressions; early defibrillation when applicable; early administration of
      drugs; appropriate airway management ensuring normoventilation; and delivery of
      appropriate post-resuscitation care to enhance survival. Of note, it is important
      to monitor the quality of the various care procedures. The resuscitation team
      needs to reduce unnecessary interruptions to chest compressions in order to
      maintain adequate coronary perfusion pressure during the ACLS drill. In addition,
      the team needs to continually look out for reversible causes of the cardiac
      arrest.

PMID- 28741000
TI  - Singapore Defibrillation Guidelines 2016.
AB  - The most common initial rhythm in a sudden cardiac arrest is ventricular
      fibrillation or pulseless ventricular tachycardia. This is potentially treatable
      with defibrillation, especially if provided early. However, any delay in
      defibrillation will result in a decline in survival. Defibrillation requires
      coordination with the cardiopulmonary resuscitation component for effective
      resuscitation. These two components, which form the key links in the chain of
      survival, have to be brought to the cardiac victim in a timely fashion. An
      effective chain of survival is needed in both the institution and community
      settings.

PMID- 28741002
TI  - Extracorporeal membrane oxygenation in cardiac arrest.
AB  - The survival of cardiac arrest patients is dependent on the efficient and timely
      application of the chain of survival. This includes early identification of
      cardiac arrest and activation of the emergency response system, high-quality
      cardiopulmonary resuscitation (CPR), rapid defibrillation, basic and advanced
      medical services, and advanced life support and post-cardiac arrest care.
      However, some patients may be refractory to these measures. Extracorporeal
      membrane oxygenation CPR (ECPR), otherwise known as extracorporeal life support,
      offers an alternative to such refractory cardiac arrest cases. As hospitals have
      limited resources, it is important to devise effective patient selection methods,
      and improve our understanding and experience of ECPR to ensure the best outcome.
      It is also vital to understand that ECPR constitutes only one component of post
      cardiac arrest care, which includes other aspects such as therapeutic hypothermia
      and early perfusion for best patient outcome.

PMID- 28741001
TI  - Singapore Neonatal Resuscitation Guidelines 2016.
AB  - We present the revised Neonatal Resuscitation Guidelines for Singapore. The 2015
      International Liaison Committee on Resuscitation Neonatal Task Force's consensus
      on science and treatment recommendations (2015), and guidelines from the American
      Heart Association and European Resuscitation Council were debated and discussed.
      The final recommendations of the National Resuscitation Council, Singapore, were
      derived after the task force had carefully reviewed the current available
      evidence in the literature and addressed their relevance to local clinical
      practice.

PMID- 28741004
TI  - Seventeen years of life support courses for nurses: where are we now?
AB  - The Life Support Course for Nurses (LSCN) equips nurses with the resuscitation
      skills to be first responders in in-hospital cardiac arrests. Seventeen years
      after the initiation of the LSCN, a confidential cross-sectional QualtricsTM
      survey was conducted in May 2016 on LSCN graduands to assess the following:
      confidence in nurse-initiated resuscitation post-LSCN; defibrillation experience
      and outcomes; and perceived barriers and usefulness of the LSCN. The majority of
      respondents reported that the course was useful and enhanced their confidence in
      resuscitation. Skills retention can be enhanced by organising frequent team-based
      resuscitation training. Resuscitation successes should be publicised to help
      overcome perceived barriers.

PMID- 28741003
TI  - Singapore Paediatric Resuscitation Guidelines 2016.
AB  - We present the revised 2016 Singapore paediatric resuscitation guidelines. The
      International Liaison Committee on Resuscitation's Pediatric Taskforce Consensus
      Statements on Science and Treatment Recommendations, as well as the updated
      resuscitation guidelines from the American Heart Association and European
      Resuscitation Council released in October 2015, were debated and discussed by the
      workgroup. The final recommendations for the Singapore Paediatric Resuscitation
      Guidelines 2016 were derived after carefully reviewing the current available
      evidence in the literature and balancing it with local clinical practice.

PMID- 28741005
TI  - The Pan-Asian Resuscitation Outcomes Study (PAROS) clinical research network:
      what, where, why and how.
AB  - Out-of-hospital cardiac arrest (OHCA) is a global health concern with an
      incidence rate of 50-60 per 100,000 person-years. To improve OHCA survival rates,
      several cardiac arrest registries have been set up in North America and Europe,
      such as the Resuscitation Outcomes Consortium, Cardiac Arrest Registry to Enhance
      Survival, Ontario Prehospital Advanced Life Support and European Registry of
      Cardiac Arrest. In Asia, however, there was previously no concerted effort in
      prehospital emergency care research owing to differences in prehospital emergency
      medical services systems, data collection methods and outcome reporting between
      countries. Recognising the need for a collaborative prehospital emergency care
      research group in Asia, researchers from seven countries in the Asia-Pacific
      region (including Japan, South Korea, Taiwan, Thailand, United Arab Emirates
      Dubai, Singapore and Malaysia) established the Pan-Asian Resuscitation Outcomes
      Study (PAROS) clinical research network in 2010. This paper gives the overview,
      methodology and research accomplishments of the PAROS network.

PMID- 28741006
TI  - Measuring the effectiveness of a novel CPRcardTM feedback device during simulated
      chest compressions by non-healthcare workers.
AB  - INTRODUCTION: There is a need for a simple-to-use and easy-to-carry CPR feedback
      device for laypersons. We aimed to determine if a novel CPRcardTM feedback device
      improved the quality of chest compressions. METHODS: We compared participants'
      chest compression rate and depth with and without feedback. Compression data was
      captured through the CPRcardTM or Resusci Anne's SimPad(r) SkillReporterTM.
      Compression quality was defined based on 2010 international guidelines for rate,
      depth and flow fraction. RESULTS: Overall, the CPRcard group achieved a better
      median compression rate (CPRcard 117 vs. control 122, p = 0.001) and proportion
      of compressions within the adequate rate range (CPRcard 83% vs. control 47%, p <
      0.001). Compared to the no-card and blinded-card groups, the CPRcard group had a
      higher proportion of adequate compression rate (CPRcard 88% vs. no-card 46.8%, p
      = 0.037; CPRcard 73% vs. blinded-card 43%, p = 0.003). Proportion of compressions
      with adequate depth was similar in all groups (CPRcard 52% vs. control 48%, p =
      0.957). The CPRcard group more often met targets for compression rate of 100
      120/min and depth of at least 5 cm (CPRcard 36% vs. control 4%, p = 0.022). Chest
      compression flow fraction rate was similar but not statistically significant in
      all groups (92%, p = 1.0). Respondents using the CPRcard expressed higher
      confidence (mean 2.7 +/- 2.4; 1 = very confident, 10 = not confident).
      CONCLUSION: Use of the CPRcard by non-healthcare workers in simulated
      resuscitation improved the quality of chest compressions, thus boosting user
      confidence in performing compressions.

PMID- 28741007
TI  - Role of peak current in conversion of patients with ventricular fibrillation.
AB  - INTRODUCTION: Peak currents are the final arbiter of defibrillation in patients
      with ventricular fibrillation (VF). However, biphasic defibrillators continue to
      use energy in joules for electrical conversion in hopes that their impedance
      compensation properties will address transthoracic impedance (TTI), which must be
      overcome when a fixed amount of energy is delivered. However, optimal peak
      currents for conversion of VF remain unclear. We aimed to determine the role of
      peak current and optimal peak levels for conversion in collapsed VF patients.
      METHODS: Adult, non-pregnant patients presenting with non-traumatic VF were
      included in the study. All defibrillations that occurred were included. Impedance
      values during defibrillation were used to calculate peak current values. The
      endpoint was return of spontaneous circulation (ROSC). RESULTS: Of the 197
      patients analysed, 105 had ROSC. Characteristics of patients with and without
      ROSC were comparable. Short duration of collapse < 10 minutes correlated
      positively with ROSC. Generally, patients with average or high TTI converted at
      lower peak currents. 25% of patients with high TTI converted at 13.3 +/- 2.3 A,
      22.7% with average TTI at 18.2 +/- 2.5 A and 18.6% with low TTI at 27.0 +/- 4.7 A
      (p = 0.729). Highest peak current conversions were at < 15 A and 15-20 A. Of the
      44 patients who achieved first-shock ROSC, 33 (75.0%) received < 20 A peak
      current vs. > 20 A for the remaining 11 (25%) patients (p = 0.002). CONCLUSION:
      For best effect, priming biphasic defibrillators to deliver specific peak
      currents should be considered.

PMID- 28741008
TI  - The National Resuscitation Council, Singapore, and 34 years of resuscitation
      training: 1983 to 2017.
AB  - Training in the modern form of cardiopulmonary resuscitation (CPR) started in
      Singapore in 1983. For the first 15 years, the expansion of training programmes
      was mainly owing to the interest of a few individuals. Public training in the
      skill was minimal. In an area of medical care where the greatest opportunity for
      benefit lies in employing core resuscitation skills in the prehospital
      environment, very little was being done to address such a need. In 1998, a group
      of physicians, working together with the Ministry of Health, set up the National
      Resuscitation Council (NRC). Over the years, the NRC has created national
      guidelines on resuscitation and reviewed them at five-yearly intervals. Provider
      training manuals are now available for most programmes. The NRC has set up an
      active accreditation system for monitoring and maintaining standards of life
      support training. This has led to a large increase in the number of training
      centres, as well as recognition and adoption of the council's guidelines in the
      country. The NRC has also actively promoted the use of bystander CPR through
      community-based programmes, resulting in a rise in the number of certified
      providers. Improving the chain of survival, through active community-based
      training programmes, will likely lead to more lives being saved from sudden
      cardiac arrest.

PMID- 28741009
TI  - The role of dispatch in resuscitation.
AB  - The role of the dispatch centre has increasingly become a focus of attention in
      cardiac arrest resuscitation. The dispatch centre is part of the first link in
      the chain of survival because without the initiation of early access, the rest of
      the chain is irrelevant. The influence of dispatch can also extend to the
      initiation of bystander cardiopulmonary resuscitation, early defibrillation and
      the rapid dispatch of emergency ambulances. The new International Liaison
      Committee on Resuscitation, the American Heart Association and, especially, the
      European Resuscitation Council 2015 guidelines have been increasing their
      emphasis on dispatch as the key to improving out-of-hospital cardiac arrest
      survival.

PMID- 28741010
TI  - Perception of a single-session pre-in vitro fertilisation counselling service and
      attitudes towards support group: a survey of patients in Singapore.
AB  - INTRODUCTION: This study aimed to investigate patients' evaluation of a
      compulsory pre-in vitro fertilisation (IVF) counselling session in Singapore and
      determine their attitudes towards attending a support group during IVF treatment.
      METHODS: 464 patients due to undergo their first IVF treatment were recruited at
      the Clinic for Human Reproduction, National University Hospital, Singapore. Prior
      to IVF treatment, all patients attended a counselling session conducted by a
      clinical psychologist trained in infertility counselling. The Depression Anxiety
      Stress Scales 21 was used to measure patients' psychological symptoms of
      depression, anxiety and stress. A feedback form was administered after the
      session to determine their evaluation of the session and interest in attending a
      support group. RESULTS: After the pre-IVF counselling session, 90.9% of patients
      reported that the session was useful, with over 80% of participants reporting
      that the session had helped them to better prepare for the IVF treatment,
      enhanced their coping and enabled them to better communicate their needs to their
      spouse. Overall, 64.1% of patients expressed interest in attending a support
      group, with male patients showing more interest. Financial resources and the
      level of psychological symptoms experienced were found to influence patients'
      motivation to attend a support group. CONCLUSION: The single pre-IVF counselling
      session was well received and found to be useful by patients. Hence, it is
      recommended that IVF counselling be made an essential part of the holistic care
      given to patients undergoing IVF, particularly those who experience higher levels
      of distressing psychological symptoms.

PMID- 28741011
TI  - Medical dispute resolution, patient safety and the doctor-patient relationship.

PMID- 28741012
TI  - Management of computed tomography-detected pneumothorax in patients with blunt
      trauma: experience from a community-based hospital.
AB  - INTRODUCTION: Diagnoses of pneumothorax, especially occult pneumothorax, have
      increased as the use of computed tomography (CT) for imaging trauma patients
      becomes near-routine. However, the need for chest tube insertion remains
      controversial. We aimed to study the management of pneumothorax detected on CT
      among patients with blunt trauma, including the decision for tube thoracostomy,
      in a community-based hospital. METHODS: Chest CT scans of patients with blunt
      trauma treated at Al Rahba Hospital, Abu Dhabi, United Arab Emirates, from
      October 2010 to October 2014 were retrospectively studied. Variables studied
      included demography, mechanism of injury, endotracheal intubation, pneumothorax
      volume, chest tube insertion, Injury Severity Score, hospital length of stay and
      mortality. RESULTS: CT was performed in 703 patients with blunt trauma. Overall,
      pneumothorax was detected on CT for 74 (10.5%) patients. Among the 65 patients
      for whom pneumothorax was detected before chest tube insertion, 25 (38.5%) needed
      chest tube insertion, while 40 (61.5%) did not. Backward stepwise likelihood
      regression showed that independent factors that significantly predicted chest
      tube insertion were endotracheal intubation (p = 0.01), non-United Arab Emirates
      nationality (p = 0.01) and pneumothorax volume (p = 0.03). The receiver operating
      characteristic curve showed that the best pneumothorax volume that predicted
      chest tube insertion was 30 mL. CONCLUSION: Chest tube was inserted in less than
      half of the patients with blunt trauma for whom pneumothorax was detected on CT.
      Pneumothorax volume should be considered in decision-making regarding chest tube
      insertion. Conservative treatment may be sufficient for pneumothorax of volume <
      30 mL.

PMID- 28741013
TI  - Prompt use of mechanical cardiopulmonary resuscitation in out-of-hospital cardiac
      arrest: the MECCA study report.
AB  - INTRODUCTION: Early use of mechanical cardiopulmonary resuscitation (CPR) for out
      of-hospital cardiac arrest (OHCA) may improve survival outcomes. Current evidence
      for such devices uses outcomes from an intention-to-treat (ITT) perspective. We
      aimed to determine whether early use of mechanical CPR using a LUCAS 2 device
      results in better outcomes. METHODS: A prospective, randomised, multicentre study
      was conducted over one year with LUCAS 2 devices in 14 ambulances and manual CPR
      in 32 ambulances to manage OHCA. The primary outcome was return of spontaneous
      circulation (ROSC). Secondary outcomes were survival at 24 hours, discharge from
      hospital and 30 days. RESULTS: Of the 1,274 patients recruited, 1,191 were
      eligible for analysis. 889 had manual CPR and 302 had LUCAS CPR. From an ITT
      perspective, outcomes for manual and LUCAS CPR were: ROSC 29.2% and 31.1% (odds
      ratio [OR] 1.09, 95% confidence interval [CI] 0.82-1.45; p = 0.537); 24-hour
      survival 11.2% and 13.2% (OR 1.20, 95% CI 0.81-1.78; p = 0.352); survival to
      discharge 3.6% and 4.3% (OR 1.20, 95% CI 0.62-2.33; p = 0.579); and 30-day
      survival 3.0% and 4.0% (OR 1.32, 95% CI 0.66-2.64; p = 0.430), respectively. By
      as-treated analysis, outcomes for manual, early LUCAS and late LUCAS CPR were:
      ROSC 28.0%, 36.9% and 24.5%; 24-hour survival 10.6%, 15.5% and 8.2%; survival to
      discharge 2.9%, 5.8% and 2.0%; and 30-day survival 2.4%, 5.8% and 0.0%,
      respectively. Adjusted OR for survival with early LUCAS vs. manual CPR was 1.47
      after adjustment for other variables (p = 0.026). CONCLUSION: This study showed a
      survival benefit with LUCAS CPR as compared to manual CPR only, when the device
      was applied early on-site.

PMID- 28741015
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): Poster Abstracts.

PMID- 28741014
TI  - Post-resuscitation care.
AB  - Following return of spontaneous circulation (ROSC) after cardiac arrest, the
      challenge is to institute measures that ensure a higher likelihood of
      neurologically intact survival. Regardless of the cause of collapse, multiple
      organ systems may be affected secondary to post-cardiac arrest syndrome.
      Interventions required for post-ROSC care are bundled into a care regimen: prompt
      identification and treatment of the cause of cardiac arrest; and treatment of
      electrolyte abnormalities. It is also essential to establish definitive airway
      management to maintain normocapnic ventilation, prevent hyperoxia, and optimise
      haemodynamic management via judicious intravenous fluids and vasoactive drugs.
      Targeted temperature management after ROSC confers neuroprotection and leads to
      improved neurological outcomes. Glycaemic control of blood glucose levels at 6-10
      mmol/L, adequate seizure management and measures to optimise neurological
      functions should be integrated into the care bundle. The interventions outlined
      can potentially lead to more patients being discharged from hospital alive with
      good neurological function.

PMID- 28741017
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): Committee of National Societies Abstracts.

PMID- 28741016
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): World Health Organization (WHO) Abstracts.

PMID- 28741018
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): Non-sponsored Symposia Abstracts.

PMID- 28741019
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): Educational Lecture Abstracts.

PMID- 28741020
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): Satellite Symposia Abstracts.

PMID- 28741021
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): Oral Communication Abstracts.

PMID- 28741022
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): Honorary Lecture Abstracts.

PMID- 28741023
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): Plenary Lectures Abstracts.

PMID- 28741025
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): ESCEO Symposia Abstracts.

PMID- 28741024
TI  - World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO
      IOF-ESCEO 2017): Meet-the-Experts Abstracts.

PMID- 28741027
TI  - WORLD CONGRESS ON OSTEOPOROSIS, OSTEOARTHRITIS AND MUSCULOSKELETAL DISEASES.

PMID- 28741028
TI  - Transfer of time-based task expectancy across different timing environments.
AB  - Recent research on time-based expectancy has shown that humans base their
      expectancies for responses on representations of temporal relations (e.g.,
      shorter vs. longer duration), rather than on representations of absolute
      durations (e.g., 500 vs. 1000 ms). In the present study, we investigated whether
      this holds also true for time-based expectancy of tasks instead of responses.
      Using a combination of the time-event correlation paradigm and the standard task
      switching paradigm, participants learned to associate two different time
      intervals with two different tasks in a learning phase. In a test phase, the two
      intervals were either globally prolonged (Experiment 1), or shortened (Experiment
      2), and they were no longer predictive for the upcoming task. In both
      experiments, performance in the test phase was better when expectancy had been
      defined in relative terms and worse when expectancy had been defined in absolute
      terms. We conclude that time-based task expectancy employs a relative, rather
      than an absolute, representation of time. Humans seem to be able to flexibly
      transfer their time-based task expectancies between different global timing
      regimes. This finding is of importance not only for our basic understanding of
      cognitive mechanisms underlying time-based task expectancy. For human-machine
      applications, these results mean that adaptation to predictive delay structures
      in interfaces survives globally speeding up or slowing down of delays due to
      different transmission rates.

PMID- 28741029
TI  - Subtrochanteric femoral shortening osteotomy combined with cementless total hip
      replacement for Crowe type IV developmental dysplasia: a retrospective study.
AB  - BACKGROUND: Total hip replacement for high dislocation of the hip presents some
      difficulties, considering patients' young ages, the abnormal hip anatomy and the
      high rate of complications. In this study, we present our experience in terms of
      clinical and radiological results in the treatment of Crowe type IV hips with
      subtrochanteric femoral shortening osteotomy and cementless total hip
      replacement. MATERIALS AND METHODS: We retrospectively reviewed 15 patients with
      Crowe type IV hip dysplasia (two bilateral cases for a total of 17 hips) treated
      with cementless total hip replacement associated with shortening subtrochanteric
      osteotomies (nine transversal and eight Z-shape osteotomies) between March 2000
      to February 2006. The mean follow-up was 88 months (range 63-133). Harris hip
      score, leg length discrepancy, neurological status, union status of the osteotomy
      and the component stability were the criteria of the evaluation. All
      complications were noted. RESULTS: The mean HHS improved from 38.3 (range 32-52)
      to 85.6 (range 69-90). The mean preoperative leg length discrepancy was of 45 mm
      (range 38-70) and reduced to a mean of 12 mm (range 9-1.6) postoperatively. All
      osteotomies resulted healed at an average of 12.3 weeks (range 10-15). No cases
      of delayed union or nonunion were detected. Two patients (11%) showed early
      symptoms of sciatic nerve palsy which resolved uneventfully in 6 months. There
      was no migrations and none of the implants required revision. CONCLUSIONS:
      Cementless THA with shortening subtrochanteric osteotomy is an effective method
      in the treatment of patients with Crowe type IV development dysplasia of the hip.
      LEVEL OF EVIDENCE: IV.

PMID- 28741030
TI  - Hidden and overall haemorrhage following minimally invasive and open
      transforaminal lumbar interbody fusion.
AB  - BACKGROUND: Hidden haemorrhage has been proved to be significant in joint
      surgery. However, when referring to lumbar interbody fusion, it is often ignored
      because of its invisibility. This randomized controlled study aimed to calculate
      and compare hidden haemorrhage following minimally invasive and open
      transforaminal lumbar interbody fusion (MIS-TLIF and open TLIF). Meanwhile, its
      clinical significance was also analyzed. MATERIALS AND METHODS: A total of 41
      patients were included in this study, then they were randomized to receive MIS
      TLIF or open TLIF, 21 and 20, respectively. For each case, total volume loss of
      red blood cell (RBC) was calculated by Gross' formula based on perioperative
      haematocrit change, then perioperative visible volume loss of RBC was calculated
      through haemorrhage volume and weight. After deducting it from total volume loss
      of RBC, hidden volume loss of RBC was obtained. Absolute amount of hidden
      haemorrhage and its ratio upon total haemorrhage, as well as indicators assessing
      clinical outcomes, including visual analogue scale (VAS) for back and leg,
      Oswestry disability index (ODI), interbody fusion rate and complication incidence
      were compared and analyzed. RESULTS: Mean hidden volume loss of RBC in MIS-TLIF
      was significantly reduced compared with open TLIF (166.7 versus 245.6 ml).
      Besides, both mean total and visible volume loss of RBC in MIS-TLIF were also
      statistically less than those in open TLIF (355.3 versus 538.6 ml; 188.6 versus
      293.0 ml). While mean ratio of hidden haemorrhage upon total haemorrhage was
      46.7% for MIS-TLIF and 44.5% for open TLIF, respectively, showing no statistical
      significance. At one week postoperatively, more significant improvements of VAS
      for back and leg, as well as ODI were seen in MIS-TLIF compared with open TLIF.
      While at final follow-up of at least 2 years, all parameters continued to improve
      and revealed no statistical difference between both surgeries. Similar interbody
      fusion rate and complication incidence were observed in both series. CONCLUSIONS:
      Besides reduced visible haemorrhage and improved clinical outcomes, MIS-TLIF also
      owns the superiority of less hidden haemorrhage, offering another advantage over
      open TLIF. LEVEL OF EVIDENCE: Level II.

PMID- 28741031
TI  - Inhibition of serotonin transporters disrupts the enhancement of fear memory
      extinction by 3,4-methylenedioxymethamphetamine (MDMA).
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) persistently improves
      symptoms of post-traumatic stress disorder (PTSD) when combined with
      psychotherapy. Studies in rodents suggest that these effects can be attributed to
      enhancement of fear memory extinction. Therefore, MDMA may improve the effects of
      exposure-based therapy for PTSD, particularly in treatment-resistant patients.
      However, given MDMA's broad pharmacological profile, further investigation is
      warranted before moving to a complex clinical population. OBJECTIVES: We aimed to
      inform clinical research by providing a translational model of MDMA's effect, and
      elucidating monoaminergic mechanisms through which MDMA enhances fear extinction.
      METHODS: We explored the importance of monoamine transporters targeted by MDMA to
      fear memory extinction, as measured by reductions in conditioned freezing and
      fear-potentiated startle (FPS) in mice. Mice were treated with selective
      inhibitors of individual monoamine transporters prior to combined MDMA treatment
      and fear extinction training. RESULTS: MDMA enhanced the lasting extinction of
      FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor
      blocked MDMA's effect on fear memory extinction. Acute inhibition of dopamine
      (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did
      not enhance extinction. Blockade of MDMA's effect by 5-HTT inhibition also
      downregulated 5-HT2A-mediated behavior, and 5-HT2A antagonism disrupted MDMA's
      effect on extinction. CONCLUSIONS: We validate enhancement of fear memory
      extinction by MDMA in a translational behavioral model, and reveal the importance
      of 5-HTT and 5-HT2A receptors to this effect. These observations support future
      clinical research of MDMA as an adjunct to exposure therapy, and provide
      important pharmacological considerations for clinical use in a population
      frequently treated with 5-HTT inhibitors.

PMID- 28741032
TI  - Elevated alcohol consumption following alcohol cue exposure is partially mediated
      by reduced inhibitory control and increased craving.
AB  - RATIONALE: Exposure to alcohol-related cues leads to increased alcohol
      consumption, and this may be partially attributable to momentarily impaired
      impulse control. OBJECTIVES: We investigated if exposure to alcohol cues would
      impair inhibitory control and if the extent of this impairment would partially
      mediate the effect of alcohol cues on subsequent voluntary alcohol consumption.
      METHODS: We recruited 81 heavy drinkers (50 female) who completed baseline
      measures of inhibitory control (stop-signal task) and subjective craving before
      random allocation to an alcohol cue exposure or control group. The alcohol cue
      exposure group then completed a second stop-signal task (with embedded alcohol
      cues) with concurrent exposure to olfactory alcohol cues, in an alcohol context.
      The control group completed a second stop-signal task (with embedded water cues),
      accompanied by exposure to water cues, in a neutral context. Then, subjective
      craving and ad libitum alcohol consumption were measured in all participants.
      RESULTS: Inhibitory control worsened (compared to baseline) to a greater extent
      in the alcohol cue exposure group compared to the control group. Craving and ad
      libitum alcohol consumption were elevated in the alcohol cue exposure group
      compared to the control group, although the group difference in alcohol
      consumption fell short of statistical significance. In support of our hypotheses,
      multiple mediation analyses demonstrated that elevated ad libitum alcohol
      consumption following alcohol cue exposure was partially mediated by both
      impaired inhibitory control and increased craving. CONCLUSIONS: These findings
      suggest that state fluctuations in inhibitory control are a potential mechanism
      through which alcohol cues increase drinking behaviour.

PMID- 28741033
TI  - Refractory sciatica caused by gluteal varicosities.
AB  - We report a case of sciatica that fulfilled the diagnostic criteria for inferior
      gluteal vein varicosities according to patient history and on magnetic resonance
      imaging. Since conservative treatment was ineffective, excision-ligation of the
      varicose vein was performed as recommended in the previous literature. However,
      pain was only slightly relieved and then aggravated. Reoperation involving wide
      release and resection of the piriformis outlet was performed. Pain resolved
      immediately thereafter. We suggest that this case of sciatica resulted from both
      piriformis entrapment and vein varicosities. The piriformis entrapment led to
      inferior gluteal vein backflow obstruction, and varicosities could have been the
      trigger of piriformis syndrome. Excision-ligation of the varicose vein and
      piriformis release were recommended.

PMID- 28741034
TI  - [Cubital tunnel syndrome : Diagnostics and therapy].
AB  - Cubital tunnel syndrome is the second most common nerve compression syndrome
      observed in the upper extremity. Mechanical irritation of the ulnar nerve is also
      found in the upper and the lower arm even though cubital tunnel syndrome is
      documented most of the time. Apart from clinical examination electrophysiological
      testing is the most important contributor to the therapy decision. Depending on
      the clinical manifestation conservative treatment with elbow splinting may be
      appropriate. In the event of persistent or advanced nerve irritation surgical
      decompression may be the sensible intervention. Open or endoscopically assisted
      in situ decompression is currently recommended as the primary intervention while
      anterior transposition of the ulnar nerve is recommended for revision surgery.

PMID- 28741035
TI  - Biomarkers of hepatic injury and function in neonatal hypoxic ischemic
      encephalopathy and with therapeutic hypothermia.
AB  - : Therapeutic hypothermia (TH) is now provided as standard care to infants with
      moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting
      neuronal injury is well recognized, but its effect on hepatic injury which occurs
      frequently in neonatal HIE is not known. Our objective was to characterize
      biomarkers of liver injury and function in the setting of neonatal HIE and to
      describe whether HIE severity and provision of TH influence these hepatic
      biomarkers. We performed a multicenter retrospective study and compared hepatic
      biomarkers obtained during the first postnatal week, according to the severity of
      HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%)
      received TH and 138 (38%) were managed at normal temperature. Most hepatic
      biomarkers and C-reactive protein (CRP) were significantly associated with the
      severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine
      aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak
      CRP concentration (p < 0.001). CONCLUSION: We observed a significant association
      between the clinical grade of HIE and biomarkers of liver metabolism and
      function. Therapeutic hypothermia was associated with delayed CRP responses and
      with lower ALT concentrations and so may have the potential to modulate hepatic
      injury. What is Known: * Ischemic hepatic injury occurs frequently as a part of
      multiorgan dysfunction in infants with hypoxic ischemic encephalopathy (HIE). *
      The neuroprotective role of therapeutic hypothermia in management of infants with
      HIE is well recognized, but the potential hepato-protective effects of
      hypothermia are unclear. What is New/What this study adds: * Therapeutic
      hypothermia was associated with lower alanine aminotransferase and albumin
      concentrations and a delayed C-reactive protein (CRP) response and so may have
      the potential to modulate hepatic injury. * An elevated CRP concentration during
      the first postnatal week may be regarded as an expected finding in moderate and
      severe HIE and, in the overwhelming majority of cases, occurs secondary to
      hepatic hypoxia-ischemia in the absence of blood culture-positive sepsis.

PMID- 28741036
TI  - Network based subcellular proteomics in monocyte membrane revealed novel
      candidate genes involved in osteoporosis.
AB  - : In this study, label-free-based quantitative subcellular proteomics integrated
      with network analysis highlighted several candidate genes including P4HB, ITGB1,
      CD36, and ACTN1 that may be involved in osteoporosis. All of them are predicted
      as significant membrane proteins with high confidence and enriched in bone
      related biological process. The results were further verified in transcriptomic
      and genomic levels. INTRODUCTION: Osteoporosis is a metabolic bone disease mainly
      characterized by low bone mineral density (BMD). As the precursors of
      osteoclasts, peripheral blood monocytes (PBMs) are supported to be important
      candidates for identifying genes related to osteoporosis. We performed
      subcellular proteomics study to identify significant membrane proteins that
      involved in osteoporosis. METHODS: To investigate the association between
      monocytes, membrane proteins, and osteoporosis, we performed label-free
      quantitative subcellular proteomics in 59 male subjects with discordant BMD
      levels, with 30 high vs. 29 low BMD subjects. Subsequently, we performed
      integrated gene enrichment analysis, functional annotation, and pathway and
      network analysis based on multiple bioinformatics tools. RESULTS: A total of 1070
      membrane proteins were identified and quantified. By comparing the proteins'
      expression level, we found 36 proteins that were differentially expressed between
      high and low BMD groups. Protein localization prediction supported the notion
      that the differentially expressed proteins, P4HB (p = 0.0021), CD36 (p = 0.0104),
      ACTN1 (p = 0.0381), and ITGB1 (p = 0.0385), are significant membrane proteins.
      Functional annotation and pathway and network analysis highlighted that P4HB,
      ITGB1, CD36, and ACTN1 are enriched in osteoporosis-related pathways and terms
      including "ECM-receptor interaction," "calcium ion binding," "leukocyte
      transendothelial migration," and "reduction of cytosolic calcium levels." Results
      from transcriptomic and genomic levels provided additional supporting evidences.
      CONCLUSION: Our study strongly supports the significance of the genes P4HB,
      ITGB1, CD36, and ACTN1 to the etiology of osteoporosis risk.

PMID- 28741037
TI  - Shifted dynamic interactions between subcortical nuclei and inferior frontal gyri
      during response preparation in persistent developmental stuttering.
AB  - Persistent developmental stuttering is associated with basal ganglia dysfunction
      or dopamine dysregulation. Here, we studied whole-brain functional connectivity
      to test how basal ganglia structures coordinate and reorganize sensorimotor brain
      networks in stuttering. To this end, adults who stutter and fluent speakers
      (control participants) performed a response anticipation paradigm in the MRI
      scanner. The preparation of a manual Go/No-Go response reliably produced activity
      in the basal ganglia and thalamus and particularly in the substantia nigra.
      Strikingly, in adults who stutter, substantia nigra activity correlated
      positively with stuttering severity. Furthermore, functional connectivity
      analyses yielded altered task-related network formations in adults who stutter
      compared to fluent speakers. Specifically, in adults who stutter, the globus
      pallidus and the thalamus showed increased network synchronization with the
      inferior frontal gyrus. This implies dynamic shifts in the response preparation
      related network organization through the basal ganglia in the context of a non
      speech motor task in stuttering. Here we discuss current findings in the
      traditional framework of how D1 and D2 receptor activity shapes focused movement
      selection, thereby suggesting a disproportional involvement of the direct and the
      indirect pathway in stuttering.

PMID- 28741038
TI  - Changes in appetite, energy intake, body composition, and circulating ghrelin
      constituents during an incremental trekking ascent to high altitude.
AB  - PURPOSE: Circulating acylated ghrelin concentrations are associated with altitude
      induced anorexia in laboratory environments, but have never been measured at
      terrestrial altitude. This study examined time course changes in appetite, energy
      intake, body composition, and ghrelin constituents during a high-altitude trek.
      METHODS: Twelve participants [age: 28(4) years, BMI 23.0(2.1) kg m-2] completed a
      14-day trek in the Himalayas. Energy intake, appetite perceptions, body
      composition, and circulating acylated, des-acylated, and total ghrelin
      concentrations were assessed at baseline (113 m, 12 days prior to departure) and
      at three fixed research camps during the trek (3619 m, day 7; 4600 m, day 10;
      5140 m, day 12). RESULTS: Relative to baseline, energy intake was lower at 3619 m
      (P = 0.038) and 5140 m (P = 0.016) and tended to be lower at 4600 m (P = 0.056).
      Appetite perceptions were lower at 5140 m (P = 0.027) compared with baseline.
      Acylated ghrelin concentrations were lower at 3619 m (P = 0.046) and 4600 m (P =
      0.038), and tended to be lower at 5140 m (P = 0.070), compared with baseline. Des
      acylated ghrelin concentrations did not significantly change during the trek (P =
      0.177). Total ghrelin concentrations decreased from baseline to 4600 m (P =
      0.045). Skinfold thickness was lower at all points during the trek compared with
      baseline (P <= 0.001) and calf girth decreased incrementally during the trek (P =
      0.010). CONCLUSIONS: Changes in plasma acylated and total ghrelin concentrations
      may contribute to the suppression of appetite and energy intake at altitude, but
      differences in the time course of these responses suggest that additional factors
      are also involved. Interventions are required to maintain appetite and energy
      balance during trekking at terrestrial altitudes.

PMID- 28741039
TI  - Association of opioid prescription and perioperative complications in obstructive
      sleep apnea patients undergoing total joint arthroplasties.
AB  - PURPOSE: Obstructive sleep apnea (OSA) has been linked to higher rates of
      perioperative complications. Practice guidelines recommend minimizing opioids in
      this cohort to reduce complications. However, a paucity of evidence exists
      relating different levels of opioid prescription to perioperative complications.
      Our aim was to investigate if different levels of opioid prescription are related
      to perioperative complication risk in patients with OSA. METHODS: A total of
      107,610 OSA patients undergoing total knee or hip arthroplasty between 2006 and
      2013 were identified in a nationwide database and divided into subgroups
      according to the amount of opioids prescribed. We then compared those subgroups
      for odds of perioperative complications using multilevel multivariable logistic
      regression models. RESULTS: OSA patients with higher levels of opioid
      prescription had increased odds for gastrointestinal complications (OR 1.90, 95%
      CI 1.47-2.46), prolonged length of stay (OR 1.64, 95% CI 1.57-1.72), and
      increased cost of care (OR 1.48, 95% CI 1.40-1.57). However, we found lower odds
      for pulmonary complications (OR 0.85, 95% CI 0.74-0.96) for the high-prescription
      group. CONCLUSIONS: Higher levels of opioid prescription were associated with
      higher odds for gastrointestinal complications and adverse effects on cost and
      length of stay but lower odds for pulmonary complications in OSA patients
      undergoing joint arthroplasties. The latter finding is unlikely causal but may
      represent more preventive measures and early interventions among those patients.
      Attempts to reduce opioid prescription should be undertaken to improve quality
      and safety of care in this challenging cohort in the perioperative setting.

PMID- 28741041
TI  - End of an enigma: Aenigmopteris belongs in Tectaria (Tectariaceae:
      Polypodiopsida).
AB  - The phylogenetic affinities of the fern genus Aenigmopteris have been the subject
      of considerable disagreement, but until now, no molecular data were available
      from the genus. Based on the analysis of three chloroplast DNA regions (rbcL,
      rps16-matK, and trnL-F) we demonstrate that Aenigmopteris dubia (the type species
      of the genus) and A. elegans are closely related and deeply imbedded in Tectaria.
      The other three species of genus are morphologically very similar; we therefore
      transfer all five known species into Tectaria. Detailed morphological comparison
      further shows that previously proposed diagnostic characters of Aenigmopteris
      fall within the range of variation of a broadly circumscribed Tectaria.

PMID- 28741040
TI  - Detection and phylogenetic analysis of Mycoplasma hyopneumoniae from Tibetan pigs
      in western China.
AB  - Enzootic pneumonia (EP), often caused by Mycoplasma hyopneumoniae, occurs in
      Tibetan pigs between October and December in Western China. The aim of this study
      was to determine the prevalence of M. hyopneumoniae in Tibetan pig herds and also
      the prevalence of infection. M. hyopneumoniae was detected using enzyme-linked
      immunosorbent assay, polymerase chain reaction (PCR), and 16S rRNA sequencing.
      Twenty-nine inflammatory gross-lesions were observed in 155 lungs of slaughtered
      pigs. Invasion of focal lymphocytes was confirmed by paraffin sectioning and
      hematoxylin-eosin staining of lung sections. Bronchoalveolar lavage fluid (BALF)
      from slaughtered Tibetan pigs and nasal swabs from others were assayed using PCR.
      The prevalence of M. hyopneumoniae in Tibetan pig herds (via ELISA) was 20.48%
      (93/454) in 3 provinces (Sichuan, Tibet autonomous region, and Qinghai) between
      October and December of 2014. The difference in prevalence among animals in six
      different growing stages was statistically significant (P < 0.05). Anti-M.
      hyopneumoniae antibody was detected in breeding sows (45.83%; 22/48) and piglets
      (50%; 3/6). PCR and gel electrophoresis of BALF showed that 6.45% (10/155) of
      pigs were positive for M. hyopneumoniae. The presence of M. hyopneumoniae in
      serum was higher in piglets and breeding sows than in any other group. In
      conclusion, the results of this study showed that M. hyopneumoniae is prevalent
      among Tibetan pigs between October and December in Western China. To the authors'
      knowledge, this is the first investigation of M. hyopneumoniae prevalence in
      Tibetan pigs of Western China using serological tests, PCR, and 16S rRNA
      sequencing.

PMID- 28741042
TI  - The first case of lymphogranuloma venereum in a woman in East-Central Europe and
      its multiple co-infections.
AB  - We are reporting the first case of lymphogranuloma venereum in women in East
      Central Europe. A 22-year-old heterosexual woman attended our department of
      venereology. She complained about a burning sensation in the urethra and vaginal
      discharge. Many tests were performed, and lymphogranuloma venereum, syphilis,
      gonorrhea, chlamydial urethritis and cervicitis, genital herpes, genital warts,
      and hepatitis C were diagnosed. Lymphogranuloma venereum was originally endemic
      in tropical and subtropical areas, but since 2003, outbreaks of this infection
      have been reported in North America, Europe, and Australia in men who have sex
      with men (MSM) community. To date, all cases of lymphogranuloma venereum in the
      Czech Republic appeared in men, predominantly in HIV-positive MSM. There are not
      many evidences about lymphogranuloma venereum (LGV) in women in developed
      countries. This report underlines the need for awareness of lymphogranuloma
      venereum in women among gynecologists, venereologists, and other physicians not
      only in Western Europe, but across all European countries.

PMID- 28741043
TI  - Comparison of Near-Infrared Imaging Camera Systems for Intracranial Tumor
      Detection.
AB  - PURPOSE: Distinguishing neoplasm from normal brain parenchyma intraoperatively is
      critical for the neurosurgeon. 5-Aminolevulinic acid (5-ALA) has been shown to
      improve gross total resection and progression-free survival but has limited
      availability in the USA. Near-infrared (NIR) fluorescence has advantages over
      visible light fluorescence with greater tissue penetration and reduced background
      fluorescence. In order to prepare for the increasing number of NIR fluorophores
      that may be used in molecular imaging trials, we chose to compare a state-of-the
      art, neurosurgical microscope (System 1) to one of the commercially available NIR
      visualization platforms (System 2). PROCEDURES: Serial dilutions of indocyanine
      green (ICG) were imaged with both systems in the same environment. Each system's
      sensitivity and dynamic range for NIR fluorescence were documented and analyzed.
      In addition, brain tumors from six patients were imaged with both systems and
      analyzed. RESULTS: In vitro, System 2 demonstrated greater ICG sensitivity and
      detection range (System 1 1.5-251 MUg/l versus System 2 0.99-503 MUg/l).
      Similarly, in vivo, System 2 demonstrated signal-to-background ratio (SBR) of 2.6
      +/- 0.63 before dura opening, 5.0 +/- 1.7 after dura opening, and 6.1 +/- 1.9
      after tumor exposure. In contrast, System 1 could not easily detect ICG
      fluorescence prior to dura opening with SBR of 1.2 +/- 0.15. After the dura was
      reflected, SBR increased to 1.4 +/- 0.19 and upon exposure of the tumor SBR
      increased to 1.8 +/- 0.26. CONCLUSION: Dedicated NIR imaging platforms can
      outperform conventional microscopes in intraoperative NIR detection. Future
      microscopes with improved NIR detection capabilities could enhance the use of NIR
      fluorescence to detect neoplasm and improve patient outcome.

PMID- 28741044
TI  - Efficacy and Tolerability of Asenapine Compared with Olanzapine in Borderline
      Personality Disorder: An Open-Label Randomized Controlled Trial.
AB  - BACKGROUND: Asenapine is a new second-generation antipsychotic that is
      understudied in borderline personality disorder (BPD). Only one study
      investigating the use of the drug in this indication (an open-label pilot study)
      has been conducted to date. OBJECTIVE: The present open-label, randomized,
      controlled trial aimed to evaluate the efficacy and tolerability of asenapine in
      comparison with olanzapine, the most broadly studied antipsychotic in BPD.
      METHODS: A total of 51 outpatients aged between 18 and 50 years with a diagnosis
      of BPD based on Diagnostic and Statistical Manual of Mental Disorders, Fifth
      Edition (DSM-5) criteria were assigned for 12 weeks to asenapine (5-10 mg/day) or
      olanzapine (5-10 mg/day). Participants were assessed at baseline and after 12
      weeks with the following instruments: the Clinical Global Impression Scale,
      Severity item (CGI-S), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety
      Rating Scale (HAM-A), Social Occupational Functioning Assessment Scale (SOFAS),
      Borderline Personality Disorder Severity Index (BPDSI), Barratt Impulsiveness
      Scale, version 11 (BIS-11), Modified Overt Aggression Scale (MOAS), Self-Harm
      Inventory (SHI), and Dosage Record and Treatment Emergent Symptom Scale (DOTES).
      Analysis of variance repeated measures was performed. Intention-to-treat analysis
      with last observation carried forward was conducted. RESULTS: There were 11 drop
      outs (21.57%): six patients taking asenapine and five patients receiving
      olanzapine. Two patients who received asenapine stopped the drug, one due to oral
      hypoesthesia and the other due to moderate anxiety. Two patients receiving
      olanzapine discontinued the treatment because of significant weight gain (>=3
      kg). The remaining seven drop-outs resulted from the lack of compliance with the
      trial prescription. Forty out of the 51 patients (78%) completed the trial: 19
      patients received asenapine, while 21 patients received olanzapine. We found a
      significant within-subject effect (trial duration) for all rating scales, except
      from the HAM-D, the MOAS, and two items of the BPDSI, namely, "identity
      disturbance" and "parasuicidal behaviors." A significant effect between subjects
      was found for the two items of the BPDSI "affective instability" and
      "dissociation/paranoid ideation." Asenapine was found superior to olanzapine in
      reducing the affective instability score (P = 0.001), whereas olanzapine was
      found superior to asenapine in reducing dissociation/paranoid ideation (P =
      0.012). However, the study was found to be underpowered to detect a difference
      between the drugs on the dissociation/paranoid ideation item of the BPDSI. Two
      patients receiving asenapine experienced akathisia and another two
      restlessness/anxiety, while three patients receiving olanzapine reported
      somnolence and two fatigue. CONCLUSIONS: Asenapine and olanzapine were
      demonstrated to have a similar efficacy. While asenapine was found to be more
      efficacious than olanzapine in treating affective instability, olanzapine was
      superior to asenapine in treating paranoid ideation and dissociation. However,
      the study was underpowered to detect a difference between groups on the
      dissociation/paranoid ideation item. Both medications were well tolerated, with
      asenapine being related to a higher frequency of oral hypoesthesia and akathisia,
      and olanzapine being prone to induce weight gain. The open-label study design,
      lack of a placebo group, and small sample size constitute major limitations of
      this trial. Our findings need to be replicated in further studies. Clinical
      Trials Registry code: ACTRN12614000551695.

PMID- 28741045
TI  - Erratum to: Assessment of individual cognitive changes after deep brain
      stimulation surgery in Parkinson's disease using the Neuropsychological Test
      Battery Vienna short version.

PMID- 28741046
TI  - Erratum to: exposure of vital cells to necrotic cell lysates induce the IRE1alpha
      branch of the unfolded protein response and cell proliferation.

PMID- 28741047
TI  - Response to Commentaries.

PMID- 28741048
TI  - Saying 'Thank You' to those whose thoughts really helped us forward.

PMID- 28741049
TI  - The assessment of renal cortex and parenchymal volume using automated CT
      volumetry for predicting renal function after donor nephrectomy.
AB  - BACKGROUND: Contrast-enhanced CT is necessary before donor nephrectomy and is
      usually combined with a Tc-99m-mercapto-acetyltriglycine (MAG3) scan to check
      split renal function (SRF). However, all transplant programs do not use MAG3
      because of its high cost and exposure to radiation. We examined whether CT
      volumetry of the kidney can be a new tool for evaluating SRF. METHODS: Sixty
      three patients underwent live donor nephrectomy. Patients without a 1.0 mm slice
      CT or follow-up for <12 months were excluded leaving 34 patients' data being
      analyzed. SRF was measured by MAG3. Split renal volume (SRV) was calculated
      automatically using volume analyzer software. The correlation between SRF and SRV
      was examined. The association between the donor's postoperative estimated
      glomerular filtration rate (eGFR) and predicted eGFR calculated by MAG3 or CT
      volumetry was analyzed at 1, 3, and 12 months post nephrectomy. RESULTS: Strong
      correlations were observed preoperatively in a Bland-Altman plot between SRF
      measured by MAG3 and either CT cortex or parenchymal volumetry. In addition, eGFR
      after donation correlated with SRF measured by MAG3 or CT volumetry. The
      correlation coefficients (R) for eGFR Mag3 split were 0.755, 0.615, and 0.763 at
      1, 3 and 12 months, respectively. The corresponding R values for cortex volume
      split were 0.679, 0.638, and 0.747. Those for parenchymal volume split were
      0.806, 0.592, and 0.764. CONCLUSION: Measuring kidney by CT volumetry is a cost
      effective alternative to MAG3 for evaluating SRF and predicting postoperative
      donor renal function. Both cortex and parenchymal volumetry were similarly
      effective.

PMID- 28741050
TI  - Risk factors for progression of chronic kidney disease in the EPPIC trials and
      the effect of AST-120.
AB  - BACKGROUND: Two randomized, double-blind, placebo-controlled trials (EPPIC-1 and
      EPPIC-2) investigated the efficacy and safety of AST-120, an oral spherical
      carbon adsorbent, in adults with chronic kidney disease (CKD). While the benefit
      of adding AST-120 to standard therapy was not supported by these trials, we
      performed a post hoc analysis to focus on CKD progression and to determine the
      risk factors for the primary endpoint in the EPPIC trial population. METHODS: In
      the EPPIC trials, patients were randomly assigned 1:1 to treatment with AST-120
      or placebo. The primary endpoint was a composite of dialysis initiation, kidney
      transplantation, or doubling of serum creatinine. The EPPIC trial pooled
      population was evaluated with the same statistical methods used for analysis of
      the primary and secondary efficacy endpoints. The trials were registered on
      ClinicalTrials.gov (NCT00500682 [EPPIC-1] and NCT00501046 [EPPIC-2]). RESULTS: An
      analysis of the placebo population suggested baseline urinary protein to urinary
      creatinine ratio (UP/UCr) >=1.0 and hematuria were independent risk factors for
      event occurrence and eGFR lowering. Analysis of the high risk patients revealed a
      difference in the primary endpoint occurrence between treatment groups, if
      angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers
      were administered (hazard ratio 0.74, 95% confidence interval 0.56-0.96). Also,
      the eGFR changes from baseline in the AST-120 group were smaller than that in the
      placebo group (P = 0.035). CONCLUSIONS: CKD progression may have an association
      with baseline UP/UCr and hematuria. Treatment with AST-120 may delay the time to
      the primary endpoint in patients with progressive CKD receiving standard therapy,
      thus warranting further investigation.

PMID- 28741051
TI  - A nationwide prospective cohort study of patients with advanced chronic kidney
      disease in Japan: The Reach-J CKD cohort study.
AB  - BACKGROUND: Epidemiology and outcomes of Japanese patients with advanced chronic
      kidney disease (CKD)-an estimated glomerular filtration rate (eGFR) < 45
      ml/min/1.73 m2-has remained largely unexamined. METHODS: We conducted a
      nationwide survey to determine the distribution of Japanese CKD patients, and are
      conducting a cohort study of these patients. A questionnaire eliciting details
      about facilities and their CKD practices was sent to all clinics/hospitals with
      nephrologists. Based on the survey results, we recruited 2400 advanced CKD
      patients receiving nephrologist care from at least 30 representative facilities
      throughout Japan, selected randomly with stratification by region and facility
      size. Through patient questionnaires and nephrologist-practice surveys aligned
      with the international CKD Outcomes and Practice Patterns Study (CKDopps), we
      shall annually or semi-annually collect patient, physician and clinic data
      prospectively, detailing CKD practices for 5 years, with a primary outcome of
      death or renal replacement therapy initiation, and secondary outcomes being
      decline of eGFR by 30% or 50%, CKD progression to CKD G5, or a cardiovascular
      event. RESULTS: Of 790 eligible, responding facilities, 330 (41.8%) treat >=80
      advanced CKD patients in the average 3-month period. Regional distribution of
      these facilities is similar to that of persons in the general population. Hence,
      the 30 facilities selected for data collection appear to be geographically
      representative in Japan. CONCLUSIONS: Our study will enhance understanding of
      various CKD practices and biological data associated with CKD progression, and
      allow international comparisons using the CKDopps platform. This will provide
      evidences to improve the health and quality of life for patients with advanced
      CKD.

PMID- 28741052
TI  - Applying near-infrared photoimmunotherapy to B-cell lymphoma: comparative
      evaluation with radioimmunotherapy in tumor xenografts.
AB  - OBJECTIVE: Radioimmunotherapy (RIT) has proven effective for patients with
      relapsed and refractory lymphoma. However, new types of therapy are strongly
      desired as B-cell lymphoma remains incurable for many patients.
      Photoimmunotherapy (PIT) is an emerging targeted cancer therapy that uses
      photosensitizer (IR700)-conjugated monoclonal antibodies (mAbs) to specifically
      kill cancer cells. To evaluate the usefulness and potential role of PIT for
      treating B-cell lymphoma in a comparison with RIT, we performed in vivo PIT and
      RIT studies with an IR700 or 90Y-conjugated anti-CD20 mAb, NuB2. METHODS: IR700
      or 90Y were conjugated to NuB2. Since cell aggressiveness greatly affects the
      therapeutic effect, we selected both an indolent (RPMI 1788) and an aggressive
      (Ramos) type of B-cell lymphoma cell line. The in vitro therapeutic effect of PIT
      and the biodistribution profiles of IR700-NuB2 were evaluated. In vivo PIT and
      RIT studies were performed with 100 or 500 MUg of IR700-NuB2 and 150 MUCi/20 MUg
      of 90Y-NuB2, respectively, in two types of B-cell lymphoma-bearing mice. RESULTS:
      The in vitro studies revealed that Ramos was more sensitive than RPMI 1788 to
      PIT. The therapeutic effect of PIT with 500 ug IR700-NuB2 was superior to any
      other therapies against aggressive Ramos tumors, whereas RIT showed the highest
      therapeutic effect in indolent RPMI 1788 tumors. Since the uptake levels and
      intratumoral distribution of IR700-NuB2 were comparable in both tumors, a
      possible cause of this difference is the tumor growth rate. The PIT with 500 ug
      (IR700-NuB2) group showed a significantly greater therapeutic effect than the PIT
      with 100 ug group due to the higher and more homogeneous tumor distribution of
      IR700-NuB2. CONCLUSIONS: PIT was effective for both indolent and aggressive B
      cell lymphoma, and the higher dose provided a better therapeutic effect. In
      aggressive tumors, PIT was more effective than RIT. Thus, PIT would be a
      promising strategy for the locoregional treatment or control of B-cell lymphoma.
      Since PIT and RIT have distinctive advantages over each other, they could play
      complementary rather than competitive roles in B-cell lymphoma treatment.

PMID- 28741053
TI  - Prediction of outcome in pediatric Hodgkin lymphoma based on interpretation of
      18FDG-PET/CT according to DeltaSUVmax, Deauville 5-point scale and IHP criteria.
AB  - OBJECTIVE: Minimizing side effects by using response-adopted therapy strategies
      plays an important role in the management of pediatric Hodgkin lymphoma (HL);
      however, the criteria for the definition of adequate or inadequate response are
      controversial. The aim of this study is to compare different methods of
      interpretation of 18F-FDG-PET/CT (PET) in the prediction of disease outcome in
      order to determine the optimum method in this regard. METHODS: Baseline, interim
      and post-treatment PET scans of 72 children were interpreted according to revised
      International Harmonization Project criteria (IHP) and Deauville criteria. Cut
      off values for changes in interim and post-treatment FDG uptake (DeltaSUVmax) in
      the prediction of progression-free survival (PFS) were measured using ROC
      analysis. Quantitative and visual data were compared with each other in the
      prediction of PFS. RESULTS: Mean interim and post-treatment DeltaSUVmax of the
      primary lesions were 77.4 +/- 19.5 and 68.8 +/- 30.4% and respective cut-off
      values were 82 and 73%. However, only post-treatment DeltaSUVmax yielded
      statistically significant results in the prediction of 3-year PFS (p = 0.043).
      Interim DeltaSUVmax was further analyzed according to the values reported in the
      literature (66 and 77%) yet statistically significant results were not reached (p
      = 0.604 and 0.431). For interim evaluation, IHP criteria was correlated to
      Deauville criteria (p = 0.002 and p = 0.001) and DeltaSUVmax (p = 0.03), whereas
      for post-treatment evaluation, significant correlation with DeltaSUVmax (p =
      0.04) but marginally significant (p = 0.055 and p = 0.058) correlation with
      Deauville criteria were achieved. Overall, 1, 3 and 5-year PFS were 95.7 +/- 0.2,
      89.6 +/- 0.4 and 80.8 +/- 0.7%, respectively. All methods demonstrated comparable
      performance in the prediction of 3-year PFS; however, interim PET using Deauville
      criteria and post-treatment PET using IHP criteria were statistically
      significant. All methods demonstrated high negative-predictive value but
      substantially low positive-predictive value. CONCLUSIONS: Deauville criteria are
      superior to other methods in the prediction of pediatric HL outcome using interim
      PET data. On the other hand, quantitative evaluation and visual evaluation by IHP
      can be used reliably at the end of the treatment. In this regard, we report the
      optimal cut-off value of SUVmax reduction as 73%.

PMID- 28741054
TI  - Multistage ECMO cannulas: first holes get it all?

PMID- 28741055
TI  - Effects of tunable excitation in carotenoids explained by the vibrational energy
      relaxation approach.
AB  - Carotenoids are fundamental building blocks of natural light harvesters with
      convoluted and ultrafast energy deactivation networks. In order to disentangle
      such complex relaxation dynamics, several studies focused on transient absorption
      measurements and their dependence on the pump wavelength. However, such findings
      are inconclusive and sometimes contradictory. In this study, we compare internal
      conversion dynamics in [Formula: see text]-carotene, pumped at the first, second,
      and third vibronic progression peak. Instead of employing data fitting algorithms
      based on global analysis of the transient absorption spectra, we apply a fully
      quantum mechanical model to treat the high-frequency symmetric carbon-carbon (C=C
      and C-C) stretching modes explicitly. This model successfully describes observed
      population dynamics as well as spectral line shapes in their time-dependence and
      allows us to reach two conclusions: Firstly, the broadening of the induced
      absorption upon excess excitation is an effect of vibrational cooling in the
      first excited state ([Formula: see text]). Secondly, the internal conversion rate
      between the second excited state ([Formula: see text]) and [Formula: see text]
      crucially depends on the relative curve displacement. The latter point serves as
      a new perspective on solvent- and excitation wavelength-dependent experiments and
      lifts contradictions between several studies found in literature.

PMID- 28741056
TI  - Chlorophyll a with a farnesyl tail in thermophilic cyanobacteria.
AB  - Photosystem II (PSII) of oxygenic photosynthetic organisms normally contains
      exclusively chlorophyll a (Chl a) as its major light-harvesting pigment. Chl a
      canonically consists of the chlorin headgroup with a 20-carbon, 4-isoprene unit,
      phytyl tail. We have examined the 1.9 A crystal structure of PSII from
      thermophilic cyanobacteria reported by Shen and coworkers in 2012 (PDB accession
      of 3ARC/3WU2). A newly refined electron density map from this structure,
      presented here, reveals that some assignments of the cofactors may be different
      from those modeled in the 3ARC/3WU2 structure, including a specific Chl a that
      appears to have a truncated tail by one isoprene unit. We provide experimental
      evidence using high-performance liquid chromatography and mass spectrometry for a
      small population of Chl a esterified to a 15-carbon farnesyl tail in PSII of
      thermophilic cyanobacteria.

PMID- 28741057
TI  - The role of angiography in the congruence of cardiovascular measurements between
      autopsy and postmortem imaging.
AB  - INTRODUCTION: Postmortem CT angiography is the method of choice for the
      postmortem imaging investigations of the cardiovascular (CV) system. However,
      autopsy still remains the gold standard for CV measurement. Nevertheless, there
      are not any studies on CV measurements on the multi-phase postmortem angiography
      (MPMCTA) which includes comparisons with autopsy. Therefore, the aim of this
      study is to compare CV measurements between the native CT scan and the three
      phases of the MPMCTA to find out which of these modalities correlate the best
      with autopsy measurements. METHODS: For this study, we selected retrospectively
      50 postmortem cases that underwent both MPMCTA and autopsy. A comparison was
      carried out between the CV measurements obtained with imaging (aorta; heart
      cavities and cardiac wall thicknesses; maximum cardiac diameter and
      cardiothoracic ratio) and at the autopsy (aorta; cardiac valves, ventricular
      thicknesses, and weight). RESULTS: Our results show that the dynamic phase
      displays an advantage for the measurement of the aortas. However, the MPMCTA is
      not accurate to measure the cardiac wall thicknesses. The measurements of the
      heart cavities show no correlation with the heart valves. The cardiothoracic
      ratio measured by the MPMCTA shows no correlation with the heart weight.
      Nevertheless, the maximum cardiac diameter exhibits a correlation with the latter
      on the venous and dynamic phase. CONCLUSIONS: These results show that only few CV
      parameters measured with imaging correlate with measurement obtained at the
      autopsy. These results indicate that in order to better estimate values obtained
      at the autopsy, we need to define new reference values for the CV measurement on
      MPMCTA.

PMID- 28741058
TI  - The increasing trend in the incidence of gastric cancer in the young population,
      not only in young Hispanic men.

PMID- 28741059
TI  - Postoperative follow-up programs improve survival in curatively resected gastric
      and junctional cancer patients: a propensity score matched analysis.
AB  - BACKGROUND: To date there is no evidence that more intensive follow-up after
      surgery for esophagogastric adenocarcinoma translates into improved survival.
      This study aimed to evaluate the impact of standardized surveillance by a
      specialized center after resection on survival. METHODS: Data of 587 patients
      were analyzed who underwent curative surgery for esophagogastric adenocarcinoma
      in our institution. Based on their postoperative surveillance, patients were
      assigned to either standardized follow-up (SFU) by the National Center for Tumor
      Diseases (SFU group) or individual follow-up by other physicians (non-SFU group).
      Propensity score matching (PSM) was performed to compensate for heterogeneity
      between groups. Groups were compared regarding clinicopathological findings,
      recurrence, and impact on survival before and after PSM. RESULTS: Of 587
      patients, 32.7% were in the SFU and 67.3% in the non-SFU group. Recurrence
      occurred in 39.4% of patients and 92.6% within the first 3 years; 73.6% were
      treated, and of those 17.1% underwent resection. In recurrent patients overall
      and post-recurrence survival (OS/PRS) was influenced by diagnostic tools (p <
      0.05), treatment (p <= 0.001), and resection of recurrence (p <= 0.001).
      Standardized follow-up significantly improved OS (84.9 vs. 38.4 months, p =
      0.040) in matched analysis and was an independent positive predictor of OS before
      and after PSM (p = 0.034/0.013, respectively). CONCLUSION: After PSM,
      standardized follow-up by a specialized center significantly improved OS. Cross
      sectional imaging and treatment of recurrence were associated with better
      outcome. Regular follow-up by cross-sectional imaging especially during the first
      3 years should be recommended by national guidelines, since early detection might
      help select patients for treatment of recurrence and even resection in few
      designated cases.

PMID- 28741060
TI  - Efficacy of Modified Wuzhuyu Decoction Granule ( ) for Migraine Patients with
      Cold and Stasis Obstructing Meridian Syndrome: A Randomized, Double-Blind,
      Placebo-Controlled Trial.
AB  - OBJECTIVE: To study the efficacy of modified Wuzhuyu Decoction Granule (, MWDG)
      in the treatment of migraine patients with cold and stasis obstructing meridian
      syndrome. METHODS: This study was a randomized, double-blind, placebo-controlled
      trial. A total of 78 migraine patients with cold and stasis obstructing meridian
      syndrome were recruited and randomly assigned by a ratio of 2:1 into a treatment
      group (51 cases) and a placebo group (27 cases). Patients in the treatment group
      were treated with MWDG while placebo granules were applied in the control group.
      The treatment course lasted for 12 weeks with a follow-up of 4 weeks. The primary
      outcome measures included frequency and days of migraine attacks and the
      secondary outcome measures were analgesics consumption and visual analogue scale
      (VAS) scores. All outcome assessments were conducted respectively at baseline,
      the 4th, 8th and 12th week, and the end of follow-up. RESULTS: In the treatment
      group, significant decrease in frequency of migraine attacks were observed since
      the 4th week and that of analgesics consumption since the 8th week (both P<0.05).
      While, in the placebo group, significant decrease in frequency of migraine
      attacks were observed since the 8th week and that of analgesics consumption since
      the 12th week (both P<0.05). No significant decrease in days of migraine attacks
      and VAS scores of migraine pain were observed in both groups. Between the two
      groups, there were significant differences in VAS scores and intensity of pain
      appeared in the 8th week (P<0.05). However, no significant differences were found
      in days and frequency of migraine attacks and analgesics consumption (P>0.05).
      CONCLUSIONS: MWDG was probably effective in the treatment of migraine especially
      for alleviating pain intensity. Furthermore, MWDG could reduce the frequency of
      migraine attacks and analgesics consumption sooner than the placebo.

PMID- 28741061
TI  - Treatment of uncomplicated recurrent urinary tract infection with Chinese
      medicine formula: A randomized controlled trial.
AB  - OBJECTIVE: To evaluate Chinese medicine (CM) formula Bazheng Powder () as an
      alternative therapeutic option for female patients with recurrent urinary tract
      infection (RUTI). METHODS: A randomized double-blinded trial was performed.
      Eligible female patients with RUTI were recruited from one hospital and two
      community health centers. By using a blocked randomization scheme, participants
      were randomized to receive a CM formula (10 herbs) for 4 weeks or antibiotics for
      1 week, followed by 3 weeks of placebo. Clinical cure rate and microbiological
      cure and recurrence after treatment were evaluated. RESULTS: A total 122 eligible
      patients were enrolled, with 61 cases in each group. The clinical cure rate by
      the intentto- treatment approach was 90.2% for the CM group and 82.0% for the
      antibiotics group (P>0.05). Bacteria were cleared from 88.5% (54/61) of patients
      in the CM group and 82.0% (50/61) in the antibiotics group. The recurrence rate
      in recovered patients at the 6-month follow-up was 9.1% (5/61) and 14.0 (7/61) in
      the CM and antibiotics groups, respectively (P>0.05). CONCLUSION: CM formula
      Bazheng Powder is a good alternative option for RUTI treatment. (Registration No.
      NCT01745328).

PMID- 28741062
TI  - Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by
      induction of G1/S cell-cycle arrest and apoptosis.
AB  - OBJECTIVE: To evaluate anti-melanoma effect of ethanol extract of Ilex
      hainanensis Merr. (IME) and elucidate its underlying mechanism. METHODS: Thirty
      six tumor-bearing mice were randomized into 6 groups (n=6) as follows: model
      group, IME 25, 50, 100, and 200 mg/kg groups and dacarbazine (DTIC) 70 mg/kg
      group. The mice in the IME treatment groups were intragastrically administered
      with IME 25, 50, 100 or 200 mg/kg per day, respectively. The mice in the DTIC
      group were intraperitoneally injected with DTIC 70 mg/kg every 2 days. The drug
      administration was lasting for 14 days. The cell viability was evaluated by 3
      (4,5-dime-thylthylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay.
      Flow cytometry was employed to detect cell cycle and apoptosis. The gene and
      protein expressions of nuclear factor kappaB-p65 (NF-kappaB-p65), Bcl-2, B-cell
      lymphomaextra large (Bcl-xL) and Bax were detected by quantitative real-time
      polymerase chain reaction and Western blot analyses. Caspases-3, -8, and -9
      activities were detected using the colorimetric method. In addition, a B16-F10
      melanoma xenograft mouse model was used to evaluate the anti-cancer activity of
      IME in vivo. Furthermore, a survival experiment of tumor-bearing mice was also
      performed to evaluate the possible toxicity of IME. RESULTS: IME significantly
      inhibited the proliferation of B16-F10 cells (P<0.01). Flow cytometric analysis
      showed that IME induced G1/S cell cycle arrest and apoptosis (both P<0.01). IME
      inhibited activation of NF-kappaB, decreased the gene and protein expressions of
      Bcl-2, Bcl-xL, and increased the gene and protein expressions of Bax (all
      P<0.01). In addition, IME induced the activation of Caspases-3, -8, and -9 in B16
      F10 cells. The study in vivo showed that IME significantly reduced tumor volume
      (P<0.01), and the inhibitory rate came up to 68.62%. IME also induced large areas
      of necrosis and intra-tumoral apoptosis that correlated with a reduction in tumor
      volume. Survival experiment showed that treatment with IME for 14 days
      significantly prolonged survival time and 20% of mice in the IME 200 mg/kg group
      were still alive until the 50th day. Notably, IME showed no apparent side-effects
      during the treatment period. CONCLUSION: IME exhibited significant anti-melanoma
      activity in vitro and in vivo, suggesting that IME might be a promising effective
      candidate with lower toxic for malignant melanoma therapy.

PMID- 28741063
TI  - Effects of Astragalus Polysaccharide on Mechanical Characterization of Liver
      Sinusoidal Endothelial Cells by Atomic Force Microscopy at Nanoscale.
AB  - OBJECTIVE: To study the effects of Astragalus polysaccharide (APS), the primary
      effective component of the Chinese herb medicine Astragalus membranaceus
      (frequently used for its anti-hepatic fibrosis effects), on nanoscale mechanical
      properties of liver sinusoidal endothelial cells (SECs). METHODS: Using
      endothelial cell medium as the control, 5 experimental groups were established
      utilizing different concentrations of APS, i.e. 12.5, 25, 50, 100, and 200
      MUg/mL. By using atomic force microscopy along with a microcantilever modified
      with a silicon dioxide microsphere as powerful tools, the value of Young's
      modulus in each group was calculated. SAS 9.1 software was applied to analyze the
      values of Young's modulus at the pressed depth of 300 nm. Environmental scanning
      electron microscopy was performed to observe the surface microtopography of the
      SECs. RESULTS: The value of Young's modulus in each APS experimental group was
      significantly greater than that of the control group: as APS concentration
      increased, the value of Young's modulus presented as an increasing trend. The
      difference between the low-concentration (12.5 and 25 MUg/mL) and high
      concentration (200 MUg/mL) groups was statistically significant (P<0.05), but no
      significant differences were observed between moderateconcentration (50 and 100
      MUg/mL) groups versus low- or high-concentration groups (P>0.05). Surface
      topography demonstrated that APS was capable of increasing the total area of
      fenestrae. CONCLUSIONS: The values of Young's modulus increased along with
      increasing concentrations of APS, suggesting that the stiffness of SECs increases
      gradually as a function of APS concentration. The observed changes in SEC
      mechanical properties may provide a new avenue for mechanistic research of anti
      hepatic fibrosis treatments in Chinese medicine.

PMID- 28741065
TI  - Coronary calcium scoring of CT attenuation correction scans: Automatic, manual,
      or visual?

PMID- 28741064
TI  - Injectable Sustained-Release Depots of PLGA Microspheres for Insoluble Drugs
      Prepared by hot-Melt Extrusion.
AB  - PURPOSE: Progesterone (PRG) was selected as a model drug to develop a long-acting
      injection system for poorly water-soluble drugs. METHODS: Microspheres with high
      density-low porosity were prepared by hot-melt extrusion (HME) combined with wet
      milling as the representative formulation, and a microcrystal suspension was also
      studied as a comparison. The morphology, particle size and distribution,
      polymorphism, drug distribution, density and porosity were characterized by
      scanning electron microscopy, laser diffraction particle size analyzer, power X
      ray diffraction and DSC respectively. The in vivo performance of the different
      formulations within 7 days after intramuscular injection was evaluated in male SD
      rats. RESULTS: The drug-loading rate of the microspheres could be as high as 40%.
      The average initial burst release of the microspheres (PLGA lactide:glycolide =
      75:25) was only 6.7% much lower than that of the microsuspension (25.7%) and a
      sustained release was exhibited for at least 7 days. The release mechanism was
      speculated to be as follows. The microspheres are a drug depot with drug
      microcrystals in the PLGA matrix which is a layer by layer honeycomb structure.
      CONCLUSIONS: Microspheres prepared by HME combined with wet-milling could achieve
      a long-term sustained release effect as a novel long-acting formulation strategy.

PMID- 28741066
TI  - Quantification of FDG uptake in patients with a suspicion of prosthetic valve
      endocarditis: Part of the problem or part of the solution?

PMID- 28741067
TI  - [Validation of interaction databases in psychopharmacotherapy].
AB  - BACKGROUND: Drug-drug interaction databases are an important tool to increase
      drug safety in polypharmacy. There are several drug interaction databases
      available but it is unclear which one shows the best results and therefore
      increases safety for the user of the databases and the patients. So far, there
      has been no validation of German drug interaction databases. GOAL: Validation of
      German drug interaction databases regarding the number of hits, mechanisms of
      drug interaction, references, clinical advice, and severity of the interaction.
      METHODS: A total of 36 drug interactions which were published in the last 3-5
      years were checked in 5 different databases. Besides the number of hits, it was
      also documented if the mechanism was correct, clinical advice was given, primary
      literature was cited, and the severity level of the drug-drug interaction was
      given. RESULTS: All databases showed weaknesses regarding the hit rate of the
      tested drug interactions, with a maximum of 67.7% hits. The highest score in this
      validation was achieved by MediQ with 104 out of 180 points. PsiacOnline achieved
      83 points, arznei-telegramm(r) 58, ifap index(r) 54 and the ABDA-database 49
      points. Based on this validation MediQ seems to be the most suitable databank for
      the field of psychopharmacotherapy. DISCUSSION: The best results in this
      comparison were achieved by MediQ but this database also needs improvement with
      respect to the hit rate so that the users can rely on the results and therefore
      increase drug therapy safety.

PMID- 28741068
TI  - Amplification of EGFR and cyclin D1 genes associated with human papillomavirus
      infection in oral squamous cell carcinoma.
AB  - Human papillomavirus (HPV) infection is associated with several genetic
      alterations including oncogene amplification, leading to increased aggression of
      tumors. Recently, a relationship between HPV infection and oncogene amplification
      has been reported, but this finding remains controversial. This study therefore
      investigated relationships between HPV infection and amplification of genes in
      the epidermal growth factor receptor (EGFR) signaling cascade in oral squamous
      cell carcinoma (OSCC). Extracted DNA from 142 formalin-fixed paraffin-embedded
      (FFPE) OSCC tissues was performed to investigate the copy number of EGFR, KRAS, c
      myc and cyclin D1 genes using real-time polymerase chain reaction (RT-PCR) and
      compared with calibrators. A tissue microarray of OSCC tissues was used for
      detection of c-Myc expression and HPV infection by immunohistochemistry and HPV
      E6/E7 RNA in situ hybridization, respectively. HPV infection was also
      investigated using PCR and RT-PCR. Of the 142 OSCC samples, 81 (57%) were HPV
      infected cases. The most frequently amplified gene was c-myc (55.6%), followed by
      cyclin D1 (26.1%), EGFR (23.9%) and KRAS (19.7%). Amplification of c-myc was
      significantly associated with levels of its protein product. EGFR amplification
      was also significantly associated with amplification of genes in the signaling
      cascade: KRAS (50.0%), c-myc (34.2%) and cyclin D1 (46.0%). Interestingly, HPV
      infection was significantly associated with amplification of both EGFR (76.5%)
      and cyclin D1 (73.0%). Only cyclin D1 amplification was significantly associated
      with severity of OSCC histopathology. HPV infection may play an important
      synergistic role in amplification of genes in the EGFR signaling cascade, leading
      to increased aggression in oral malignancies.

PMID- 28741069
TI  - MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in
      vitro angiogenesis through modulating the mTOR/HIF-1alpha/VEGF signaling axis in
      breast cancer cells.
AB  - BACKGROUND: Human mesenchymal stem cells (MSCs) have been shown to be involved in
      the formation and modulation of tumor stroma and in interacting with tumor cells,
      partly through their secretome. Exosomes are nano-sized intraluminal multi
      vesicular bodies secreted by most types of cells and have been found to mediate
      intercellular communication through the transfer of genetic information via
      coding and non-coding RNAs to recipient cells. Since exosomes are considered as
      protective and enriched sources of shuttle microRNAs (miRNAs), we hypothesized
      that exosomal transfer of miRNAs from MSCs may affect tumor cell behavior,
      particularly angiogenesis. METHODS: Exosomes derived from MSCs were isolated and
      characterized by scanning electron microscopy analyses, dynamic light scattering
      measurements, and Western blotting. Fold changes in miR-100 expression levels
      were calculated in exosomes and their corresponding donor cells by qRT-PCR. The
      effects of exosomal transfer of miR-100 from MSCs were assessed by qRT-PCR and
      Western blotting of the mTOR/HIF-1alpha/VEGF signaling axis in breast cancer
      cells. The quantification of secreted VEGF protein was determined by enzyme
      linked immunosorbent assay. The putative paracrine effects of MSC-derived
      exosomes on tumor angiogenesis were explored by in vitro angiogenesis assays
      including endothelial cell proliferation, migration and tube formation assays.
      RESULTS: We found that MSC-derived exosomes induce a significant and dose
      dependent decrease in the expression and secretion of vascular endothelial growth
      factor (VEGF) through modulating the mTOR/HIF-1alpha signaling axis in breast
      cancer-derived cells. We also found that miR-100 is enriched in MSC-derived
      exosomes and that its transfer to breast cancer-derived cells is associated with
      the down-regulation of VEGF in a time-dependent manner. The putative role of
      exosomal miR-100 transfer in regulating VEGF expression was substantiated by the
      ability of anti-miR-100 to rescue the inhibitory effects of MSC-derived exosomes
      on the expression of VEGF in breast cancer-derived cells. In addition, we found
      that down-regulation of VEGF mediated by MSC-derived exosomes can affect the
      vascular behavior of endothelial cells in vitro. CONCLUSIONS: Overall, our
      findings suggest that exosomal transfer of miR-100 may be a novel mechanism
      underlying the paracrine effects of MSC-derived exosomes and may provide a means
      by which these vesicles can modulate vascular responses within the
      microenvironment of breast cancer cells.

PMID- 28741070
TI  - Late-onset X-linked adrenal hypoplasia (DAX-1, NR0B1): two new adult-onset cases
      from a single center.
AB  - PURPOSE: DAX-1 (NR0B1) is an orphan nuclear receptor, which plays a critical role
      in development and regulation of the adrenal gland and hypothalamo-pituitary
      gonadal axis. Mutations in NR0B1 lead to adrenal hypoplasia congenita (AHC),
      hypogonadotropic hypogonadism (HH) and azoospermia in men. Presentation is
      typically with adrenal insufficiency (AI) during infancy or childhood. To date
      only eight cases/kindreds are reported to have presented in adulthood. METHODS:
      We describe two new cases of men with DAX-1 mutations who presented in adulthood
      and who were diagnosed at a large University Hospital. RESULTS: Case 1 presented
      with AI at 19 years. At 38 years he was diagnosed with HH. Detailed history
      revealed a brother diagnosed with AI at a similar age. Sequencing of the DAX-1
      (NR0B1) gene revealed a heterozygous c.775T > C substitution in exon 1, which
      changes codon 259 from serine to proline (p.Ser259Pro). Case 2 was diagnosed with
      AI at 30 years. Aged 37 years he presented with HH and azoospermia. He was
      treated with gonadotropin therapy but remained azoospermic. Testicular biopsy
      showed maturational arrest and hypospermatogenesis. Analysis of the NR0B1 gene
      showed a heterozygous c.836C > T substitution in exon 1, resulting in a change of
      codon 279 from proline to leucine (p.Pro279Leu). This change alters the structure
      of the repression helix domain of DAX-1 and affects protein complex interactions
      with NR5A family members. CONCLUSIONS: We describe two missense mutations within
      the putative carboxyl-terminal ligand binding domain of DAX-1, presenting with
      AHC and HH in adulthood, from a single center. DAX-1 mutations may be more
      frequent in adults than previously recognized. We recommend testing for DAX-1
      mutations in all adults with primary AI and HH or impaired fertility where the
      etiology is unclear.

PMID- 28741071
TI  - A multicenter, observational study of lanreotide depot/autogel (LAN) in patients
      with acromegaly in the United States: 2-year experience from the SODA registry.
AB  - PURPOSE: This analysis evaluates the 2-year effectiveness and safety of
      lanreotide depot/autogel (LAN), as well as treatment convenience and acromegaly
      symptom relief, from the Somatuline(r) Depot for Acromegaly (SODA) registry, a
      post-marketing, open-label, observational, multicenter, United States registry
      study. METHODS: Patients with acromegaly treated with LAN were eligible for
      enrollment. Demographics, LAN dose, extended dosing interval (EDI) (interval of
      injections >=42 days), insulin-like growth factor 1 (IGF-1), growth hormone (GH),
      glycated hemoglobin, adverse events (AEs), injection convenience, and symptom
      data were collected. RESULTS: As of September 29, 2014, 241 patients were
      enrolled in SODA. IGF-1 levels below age- and gender-adjusted upper normal limit
      (ULN) were achieved in 71.2% at month (M) 12 and 74.4% at M24; GH <=2.5 ug/L in
      83.3% at M12 and 80.0% at M24; GH <1.0 ug/L in 61.7% at M12 and 61.4% at M24.
      Both IGF-1 < ULN and GH <=2.5 ug/L were achieved in 65.0% at M12 and 54.8% at
      M24; both IGF-1 < ULN and GH < 1.0 ug/L were achieved in 51.7 and 42.9% at M12
      and M24, respectively. EDI regimen was 5.0% at baseline and 12.0% at M24. At M24,
      acromegaly symptoms appeared stable or improved. The most common AE was
      arthralgia (25.7%). Among 106 serious AEs reported by 42 patients, 10 were deemed
      related to therapy in 9 patients. At M24, 73.1% of patients rated LAN as
      convenient. CONCLUSIONS: SODA indicates 2-year biochemical control with majority
      of patients achieving both IGF-1 < ULN and GH <=2.5 ug/L. LAN was generally well
      tolerated with no new or unexpected safety signals reported during the
      observation period. clinicaltrials.gov Clinical Trial Identifier: NCT00686348.

PMID- 28741072
TI  - [The 69th Congress-urologists nominated for the Nobel Prize : Not everyone got a
      prize: four biographical sketches].
AB  - Our research group has reconstructed why the board certified urologists Werner
      Forssmann (1904-1979) and Charles Huggins (1901-1997) received the Nobel Prize in
      physiology or medicine (1956, and 1966, respectively). But the history of
      "Urology and the Nobel Prize" is in fact more multifaceted than the success
      stories of these two laureates suggest. James Israel (1848-1926), Berlin, Felix
      Guyon (1831-1920), Paris, Peter J. Freyer (1852-1921), London and Edwin Beer
      (1876-1938), New York were nominated for the award during the first three decades
      of the 20th century. Their candidacies mirror trends among leading urologists
      during the time when urology became a specialty in its own right.

PMID- 28741073
TI  - The Network Survival Method for Estimating Adult Mortality: Evidence From a
      Survey Experiment in Rwanda.
AB  - Adult death rates are a critical indicator of population health and well-being.
      Wealthy countries have high-quality vital registration systems, but poor
      countries lack this infrastructure and must rely on estimates that are often
      problematic. In this article, we introduce the network survival method, a new
      approach for estimating adult death rates. We derive the precise conditions under
      which it produces consistent and unbiased estimates. Further, we develop an
      analytical framework for sensitivity analysis. To assess the performance of the
      network survival method in a realistic setting, we conducted a nationally
      representative survey experiment in Rwanda (n = 4,669). Network survival
      estimates were similar to estimates from other methods, even though the network
      survival estimates were made with substantially smaller samples and are based
      entirely on data from Rwanda, with no need for model life tables or pooling of
      data from other countries. Our analytic results demonstrate that the network
      survival method has attractive properties, and our empirical results show that
      this method can be used in countries where reliable estimates of adult death
      rates are sorely needed.

PMID- 28741074
TI  - Concurrent chemoradiotherapy with weekly nedaplatin versus radiotherapy alone in
      elderly patients with non-small-cell lung cancer.
AB  - PURPOSE: We conduct this study to compare the efficacy and toxicity of intensity
      modulated radiotherapy (IMRT) concurrent weekly nedaplatin (NDP) versus IMRT
      alone in the stage III/IV non-surgical elderly patients with non-small-cell lung
      cancer (NSCLC). METHODS: 117 patients were enrolled into our study. The patients
      were assigned into two different groups: radiotherapy (RT) group and
      chemoradiotherapy (CRT) group. Patients in RT group were treated with IMRT at a
      single daily dose of 2 Gy for 5 days per week, totally 52-66 Gy. The CRT group,
      IMRT concurrent weekly NDP at a dose of 25 mg/m2. RESULTS: In CRT group, the
      median survival was 11.0 months (95% confidence interval [CI], 8.894-13.106
      months) and in RT group, it was 7.0 months (95% CI 5.771-8.229 months). The 1
      year, 2-year, 3-year, survival rates in the combined treatment arm were higher
      than the radiation therapy arm (46.8 vs 25.9%, 25.1 vs 11.8%, 14.7 vs 8.0%; p <
      0.001). The Cox's multiple regression analysis showed that CRT had significantly
      better overall survival than RT (HR 0.523; 95.0% CI 0.338-0.807; p = 0.003). The
      objective response rate provided that 73.3% treated with CRT compared with 51.1%
      (p = 0.018) received RT alone. Of the hematologic toxicities, leukocytes (35.0 vs
      0%; p < 0.001), neutrophils (33.3 vs 0%; p < 0.001) were significantly more
      common in the CRT group than the RT group. CONCLUSIONS: We first discovered that
      NDP concurrent IMRT for treating stage III/IV non-surgical elderly patients with
      NSCLC was good curative effect of better objective response rate and well
      tolerated. However, within the low number of patients, only stage IV gained a
      survival benefit.

PMID- 28741075
TI  - Brain relaxometry after macrocyclic Gd-based contrast agent.
AB  - PURPOSE: To assess if ratios of T1-weighted (T1w) signal intensity (SI) and
      quantitative T1 relaxometry (qT1) change on serial administration of macrocyclic
      gadobutrol. METHODS: A total of 17 glioblastoma patients were scanned at 3.0 T
      magnetic resonance imaging (MRI) every 6 weeks after tumor resection with
      standard MRI and T1 and T2 relaxometry before and after gadobutrol
      administration. On co-registered images T1w SI was measured and relaxation times
      T1 (qT1) and quantitative T2 (qT2) were quantified in several deep grey matter
      nuclei as ratios relative to frontal white matter and to the pons. Ratio changes
      were evaluated over time with a paired t-test and multiple regression. RESULTS:
      An average of 8 (range 5-14) scans per patient were completed. Ratios of T1w SI,
      qT1 and qT2 remained unchanged for all target regions from the first to the last
      time point (p > 0.05) and did not correlate with the number of gadobutrol
      administrations. Multivariate regression showed no significant impact of
      gadobutrol on qT1 or qT2 ratios, but a significant negative effect on T1w SI
      ratios. Gender also had no impact on the ratios but age had a significant
      negative influence on the qT1 ratio. CONCLUSION: Multiple administrations of a
      macrocyclic contrast agent did not change relaxation time T1 ratios in any deep
      grey matter structure.

PMID- 28741076
TI  - Detection of Verticillium species in Swedish soils using real-time PCR.
AB  - Verticillium species are soilborne plant pathogens, responsible for big yield
      losses worldwide. Here, we report improved procedures to generate DNA from
      Verticillium species imbedded in farm soils. Using new genomic sequence
      information, primers for V. dahliae, V. albo-atrum, V. tricorpus, and V.
      longisporum were designed. In a survey of 429 samples from intensively farmed
      soil of two Swedish regions, only V. dahliae and V. longisporum were identified.
      A bias towards V. longisporum (40%) was seen in the south, whereas V. dahliae was
      more frequent in the western region (19%). Analyses of soil and leaf samples from
      20 sugar beet fields, where foliar wilting had been observed, revealed V. dahliae
      DNA in all leaf and soil samples and V. longisporum in 18 soil samples,
      illustrating host choice and longevity of the V. longisporum microsclerotia. This
      study demonstrates the applicability of new molecular diagnostic tools that are
      important for growers of variable crops.

PMID- 28741077
TI  - [Chronic acromioclavicular joint injury of Rockwood V type with concomitant
      chronic anterior sternoclavicular instability].
AB  - Bipolar dislocation of the clavicle is rare. In the literature, every reported
      bipolar dislocation of the clavicle is caused by a traumatic injury with loss of
      function of the affected shoulder. Currently, there is no recommendation to
      treat. A conservative treatment can be tried first to achieve adequate shoulder
      function. If this cannot be achieved, surgical treatment will be indicated. In
      the literature, many options for surgical treatment are described. This article
      presents a case of a chronic Rockwood V injury with chronic anterior
      sternoclavicular joint instability. The special feature of this case was the
      arthroscopically assisted stabilization of the acromioclavicular joint (ACJ) with
      the ipsilateral semitendinosus tendon graft and the open stabilization of the
      sternoclavicular joint (SCJ) with the ipsilateral gracilis tendon graft. A
      lateral fracture of the clavicle in the course of the postoperative treatment was
      treated with a plate osteosynthesis. At follow-up after six months, the
      postoperative shoulder function was restored. The ACJ and the SCJ were stable in
      clinical and radiographic examination. This case report shows the first surgical
      treatment using two tendon grafts for combined stabilization of the ACJ and SCJ.

PMID- 28741078
TI  - [Analysis of 2000 surgically treated proximal femoral fractures : Multiple
      variables influence mortality].
AB  - BACKGROUND: Due to demographic change, more proximal femoral fractures can be
      expected in the future. However, accurate growth rates as well as follow-up
      research extending more than 1 year postsurgery are still lacking. MATERIALS AND
      METHODS: First, we defined inclusion and exclusion criteria for the retrospective
      cohort study. Based on these, we collected all surgical interventions conducted
      between 1 January 2006 and 31 December 2015. For a total of 2000 consecutive
      procedures, we retrieved and analysed a total of 12 variables influencing
      mortality. Data were retrieved from the prospectively established database; all
      patients still alive were contacted by phone, and missing data were collected.
      The endpoint of the study was consistently set for all patients at 2 years
      postsurgery. RESULTS: The follow-up rate was 100%. Growth rate increased by 74.1%
      over a period of 10 years. Mean age of the total population was 79.4 years, and
      women were predominantly affected (71.7%). Surgical treatment was based on
      osteosynthesis procedures (57%) using DHS, PFN, or screws, as well as on
      arthroplasty (43%) performing total hip arthroplasty or implanting large-head
      prostheses. The revision rate was 14.5%, and mortality 2 years postsurgery was
      32.4%. Through a multivariate analysis (Cox regression), the following seven
      influence factors showed statistically significant impact on mortality: age >82
      years, male gender, CRP >10 mg/dl, haemoglobin <12 g/dl, ASA 3 or 4, dementia,
      and postoperative infection-but not timing of surgery. CONCLUSION: The growth
      rate of proximal femoral fractures progressed more rapidly than expected. Through
      a multivariate analysis, a total of six intrinsic variables were verified, which
      influenced the mortality. The prevention of infection-as the only additional
      extrinsic factor in this study-represents a more important role than early
      surgical treatment.

PMID- 28741079
TI  - Characterization of the first-order visual interneurons in the visual system of
      the bumblebee (Bombus terrestris).
AB  - The bumblebee (Bombus terrestris) has become a common model animal in the study
      of various aspects of vision and visually guided behavior. Although the bumblebee
      visual system has been studied to some extent, little is known about the
      functional role of the first visual neuropil, the lamina. In this work, we
      provide an anatomical and electrophysiological description of the first-order
      visual interneurons, lamina monopolar cells (LMCs), of the bumblebee. Using
      intracellular recording coupled with dye injection, we found that bumblebee LMCs
      morphologically resemble those found in the honeybee, although only the LMC type
      L1 cells could be morphologically matched directly between the species. LMCs
      could also be classified on the basis of their light response properties as
      spiking or non-spiking. We also show that some bumblebee LMCs can produce spikes
      during responses to stimulation with naturalistic light contrasts, a property
      unusual for these neurons.

PMID- 28741080
TI  - Transcriptomic analyses reveal clathrin-mediated endocytosis involved in
      symbiotic seed germination of Gastrodia elata.
AB  - BACKGROUND: Gastrodia elata is a well-known medicinal orchid. In nature, the
      germination rate of G. elata is extremely poor, because there is no endosperm
      within the mature seed. It is crucial for G. elata to obtain nutrition from
      mycorrhizal fungi (Mycena) at the early-stage of germination. After germination,
      the seed gives rise to a protocorm. However, there are no "omic" studies on
      understanding the interaction between Gastrodia and Mycena. Here, we used
      transcriptomic approaches to explore changes in seed germination of G. elata.
      RESULTS: Based on RNA-Seq, a total of ~221 million clean reads were assembled
      denovo into 139,756 unigenes, including 42,140 unigenes that were annotated in
      public databases. Meanwhile, 1750 unigenes were identified as differentially
      expressed genes. Most of these differentially expressed genes were putatively
      involved in energy metabolism, plant defense, molecular signaling, and secondary
      metabolism. Additionally, numerous genes involved in clathrin-mediated
      endocytosis were identified from our data. Most of these genes (e.g., clathrin,
      adaptor protein, dynamin, HSC70) were basally expressed in seeds and highly
      expressed in protocorms. CONCLUSIONS: Our data suggested that clathrin-mediated
      endocytosis could play important roles in symbiotic seed germination of G. elata
      with Mycena infections.

PMID- 28741081
TI  - Capuchin monkeys' use of human and conspecific cues to solve a hidden object
      choice task.
AB  - Learning by watching others can provide valuable information with adaptive
      consequences, such as identifying the presence of a predator or locating a food
      source. The extent to which nonhuman animals can gain information by reading the
      cues of others is often tested by evaluating responses to human gestures, such as
      a point, and less often evaluated by examining responses to conspecific cues. We
      tested whether ten brown capuchin monkeys (Cebus [Sapajus] apella) were able to
      use cues from monkeys and a pointing cue from a human to obtain hidden rewards. A
      monkey could gain access to a reward hidden in one of two locations by reading a
      cue from a conspecific (e.g., reaching) or a human pointing. We then tested
      whether they could transfer this skill from monkeys to humans, from humans to
      monkeys, and from one conspecific to another conspecific. One group of monkeys
      was trained and tested using a conspecific as the cue-giver and was then tested
      with a human cue-giver. The second group of monkeys was trained and tested with a
      human cue-giver and was then tested with a monkey cue-giver. Monkeys that were
      successful with a conspecific cue-giver were also tested with a novel conspecific
      cue-giver. Monkeys learned to use a human point and conspecific cues to obtain
      rewards. Monkeys that had learned to use the cues of a conspecific to obtain
      rewards performed significantly better than expected by chance when they were
      transferred to the cues of a novel conspecific. Monkeys that learned to use a
      human point to obtain rewards performed significantly better than expected by
      chance when tested while observing conspecific cues. Some evidence suggested that
      transferring between conspecific cue-givers occurred with more facility than
      transferring across species. Results may be explained by simple rules of
      association learning and stimulus generalization; however, spontaneous flexible
      use of gestures across conspecifics and between different species may indicate
      capuchins can generalize learned social cues within and partially across species.

PMID- 28741082
TI  - Dietary total antioxidant capacity and incidence of chronic kidney disease in
      subjects with dysglycemia: Tehran Lipid and Glucose Study.
AB  - PURPOSE: We aimed to investigate the association of dietary total antioxidant
      capacity (TAC) with incidence of CKD in subjects with dysglycemia. METHODS: We
      followed-up 1179 subjects aged >=30 years with dysglycemia from the Tehran Lipid
      and Glucose Study (TLGS) for 3 years, who were initially free of CKD. Dietary
      intakes of TAC, vitamin C, vitamin E, and beta-carotene were assessed by a food
      frequency questionnaire at the baseline. Dietary TAC was estimated using the
      oxygen radical absorbance capacity method. Estimated glomerular filtration rate
      (eGFR) was calculated, using the Modification of Diet in Renal Disease Study
      equation and CKD was defined as eGFR <60 mL/min/1.73 m2. Odds ratios (ORs) using
      multivariable logistic regression were reported for the association of incident
      CKD with dietary TAC. RESULTS: A total of 197 (16.7%) cases of incident CKD were
      recorded after 3 years of follow-up. After adjustment for age, sex, smoking,
      physical activity, body mass index, hypertension, and total energy intake, the
      top tertile of dietary TAC compared to the bottom was associated with 39% [95%
      confidence interval (CI) = 0.40-0.93] lower risk of incident CKD (P for trend =
      0.025). Furthermore, the highest tertile of vitamin C intake compared to the
      lowest risk of incident CKD was decreased (OR 0.60; 95% CI 0.38-0.93, P trend
      0.023). Intakes of vitamin E and beta-carotene were not significantly associated
      with incident CKD risk. CONCLUSION: Our findings suggest that diets high in TAC
      are associated with a lower risk of incident CKD among subjects with
      hyperglycemia after 3 years of follow-up.

PMID- 28741083
TI  - Construction of bioengineered yeast platform for direct bioethanol production
      from alginate and mannitol.
AB  - Brown macroalgae are a sustainable and promising source for bioethanol production
      because they are abundant in ocean ecosystems and contain negligible quantities
      of lignin. Brown macroalgae contain cellulose, hemicellulose, mannitol,
      laminarin, and alginate as major carbohydrates. Among these carbohydrates, brown
      macroalgae are characterized by high levels of alginate and mannitol. The direct
      bioconversion of alginate and mannitol into ethanol requires extensive
      bioengineering of assimilation processes in the standard industrial microbe
      Saccharomyces cerevisiae. Here, we constructed an alginate-assimilating S.
      cerevisiae recombinant strain by genome integration and overexpression of the
      genes encoding endo- and exo-type alginate lyases, DEH (4-deoxy-L-erythro-5
      hexoseulose uronic acid) transporter, and components of the DEH metabolic
      pathway. Furthermore, the mannitol-metabolizing capacity of S. cerevisiae was
      enhanced by prolonged culture in a medium containing mannitol as the sole carbon
      source. When the constructed strain AM1 was anaerobically cultivated in a
      fermentation medium containing 6% (w/v) total sugars (approximately 1:2 ratio of
      alginate/mannitol), it directly produced ethanol from alginate and mannitol,
      giving 8.8 g/L ethanol and yields of up to 32% of the maximum theoretical yield
      from consumed sugars. These results indicate that all major carbohydrates of
      brown macroalgae can be directly converted into bioethanol by S. cerevisiae. This
      strain and system could provide a platform for the complete utilization of brown
      macroalgae.

PMID- 28741084
TI  - Towards the prediction of flow-induced shear stress distributions experienced by
      breast cancer cells in the lymphatics.
AB  - Tumour metastasis in the lymphatics is a crucial step in the progression of
      breast cancer. The dynamics by which breast cancer cells (BCCs) travel in the
      lymphatics remains poorly understood. The goal of this work is to develop a model
      capable of predicting the shear stresses metastasising BCCs experience using
      numerical and experimental techniques. This paper models the fluidic transport of
      large particles ([Formula: see text] where [Formula: see text] is the particle
      diameter and W is the channel width) subjected to lymphatic flow conditions
      ([Formula: see text]), in a [Formula: see text] microchannel. The feasibility of
      using the dynamic fluid body interaction (DFBI) method to predict particle motion
      was assessed, and particle tracking experiments were performed. The experiments
      found that particle translational velocity decreased from the undisturbed fluid
      velocity with increasing particle size (5-14% velocity lag for [Formula: see
      text]). DFBI simulations were found to better predict particle behaviour than
      theoretical predictions; however, mesh restrictions in the near-wall region
      ([Formula: see text]) result in computationally expensive models. The simulations
      were in good agreement with the experiments ([Formula: see text] difference)
      across the channel ([Formula: see text]), with differences up to 25% in the near
      wall region. Particles experience a range of shear stresses (0.002-0.12 Pa) and
      spatial shear gradients ([Formula: see text]) depending on their size and radial
      position. The predicted shear gradients are far in excess of values associated
      with BCC apoptosis ([Formula: see text]). Increasing our understanding of the
      shear stress magnitudes and gradients experienced by BCCs could be leveraged to
      elucidate whether a particular BCC size or location exists that encourages
      metastasis within the lymphatics.

PMID- 28741085
TI  - The effect of sleep deprivation on retrieval of emotional memory: a behavioural
      study using film stimuli.
AB  - Although the deleterious effects of sleep deprivation on memory consolidation are
      well documented, it is still unclear how the facilitating effect of emotions on
      memory consolidation processes could be modulated by the lack of sleep. In this
      study, we investigated the effects of sleep deprivation on episodic memory using
      emotional and non-emotional film stimuli. Forty-eight healthy subjects, divided
      into a sleep group (SG) and a sleep-deprived (SD) group, completed an Encoding
      and a Recall phase. Participants in the SD group were sleep deprived the night
      immediately following the Encoding phase, whereas the control group slept at
      home. The Recall phase was administered to all subjects 48 h after the Encoding.
      During the Encoding phase, six film clips of different valence (two positive, two
      neutral and two negative) were presented to the participants. During the Recall
      phase, episodic memory was assessed by a recognition task. Results showed that
      the SD group had a lower discrimination memory performance for all stimuli
      compared to the SG, confirming the deleterious effect of sleep deprivation on
      episodic memory consolidation. Therefore, lack of sleep severely impairs the
      consolidation of both emotional and neutral memories, as valence-related effects
      on memory consolidation were not observed after sleep deprivation.

PMID- 28741086
TI  - Statewide Policy Change in Pediatric Dental Care, and the Impact on Pediatric
      Dental and Physician Visits.
AB  - Introduction In 2007, the California signed legislation mandating a dental visit
      for all children entering kindergarten or first grade; no such mandate was made
      for physician visits. This study examines the impact of this policy change on the
      risk factors associated with obtaining pediatric dental and physician health care
      visits. Methods Every 2 years, California Health Interview Survey conducts a
      statewide survey on a representative community sample. This cross-sectional study
      took advantage of these data to conduct a "natural experiment" assessing the
      impact of this policy change on both pediatric physician and dental care visits
      in the past year. Samples included surveys of adults and children (ages 5-11) on
      years 2005 (n = 5096), 2007 (n = 4324) and 2009 (n = 4100). Results Although few
      changes in risk factors were noted in pediatric physician visits, a gradual
      decrease in risk factors was found in pediatric dental visits from 2005 to 2009.
      Report of no dental visit was less likely for: younger children (OR -0.81, CI
      0.75-0.88), insured children (OR 0.34, CI 0.22-0.53), and children who had a
      physician's visit last year (OR 0.37, CI 0.25-0.53) in 2005. By 2007, absence of
      insurance was the only risk factor related to having no dental visit (OR 0.34, CI
      0.19-0.61). By 2009, no a priori measured risk factors were associated with not
      having a dental visit for children aged 5-11 years. Conclusions A statewide
      policy mandating pediatric dental visits appears to have reduced disparities. A
      policy for medical care may contribute to similar benefits.

PMID- 28741087
TI  - The performance of different anti-dsDNA autoantibodies assays in Chinese systemic
      lupus erythematosus patients.
AB  - To compare the performance of different commercial anti-dsDNA autoantibody
      assays, including multiplex-based immunoassay (Bio-Plex), Farr radioimmunoassay
      (Farr), ELISA, chemiluminescent immunoassay (CLIA), and Crithidia Luciliae
      indirect immunofluorescence test (CLIFT) in Chinese patients with systemic lupus
      erythematosus (SLE). SLE patients (n = 119) as well as healthy controls (n = 200)
      and disease controls (n = 100) were recruited, and serum anti-dsDNA
      autoantibodies were detected by Bio-Plex, Farr, two ELISA assays (Medical &
      Biological Laboratories-ELISA, EUROIMMU-ELISA), CLIA, and a standard CLIFT. The
      correlation of anti-dsDNA autoantibody levels to SLE disease activity was
      calculated, and the specificity and sensitivity of these methods were measured by
      receiver-operator characteristic (ROC) curve analysis. In ROC curve analysis, Bio
      Plex showed the largest area under the curve (AUC) over other assays. Cutoff
      adjustment according to ROC enhanced the performance of all quantitative assays.
      Overall, Bio-Plex and CLIFT have higher specificity (>90.00%). ELISA and CLIA
      results are correlated with disease activity, and Bio-Plex results have the
      strongest correlation with SLEDAI score and active renal involvement. Bio-Plex
      assay has better overall performance in anti-dsDNA detection over Farr, ELISA,
      and CLIA methods in Chinese SLE patients.

PMID- 28741088
TI  - The autoimmune/inflammatory syndrome induced by adjuvants (ASIA)/Shoenfeld's
      syndrome: descriptive analysis of 300 patients from the international ASIA
      syndrome registry.
AB  - The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is a recently
      identified condition in which the exposure to an adjuvant leads to an aberrant
      autoimmune response. We aimed to summarize the results obtained from the ASIA
      syndrome registry up to December 2016, in a descriptive analysis of 300 cases of
      ASIA syndrome, with a focus on the adjuvants, the clinical manifestations, and
      the relationship with other autoimmune diseases. A Web-based registry, based on a
      multicenter international study, collected clinical and laboratory data in a form
      of a questionnaire applied to patients with ASIA syndrome. Experts in the disease
      validated all cases independently. A comparison study regarding type of adjuvants
      and differences in clinical and laboratory findings was performed. Three hundred
      patients were analyzed. The mean age at disease onset was 37 years, and the mean
      duration of time latency between adjuvant stimuli and development of autoimmune
      conditions was 16.8 months, ranging between 3 days to 5 years. Arthralgia,
      myalgia, and chronic fatigue were the most frequently reported symptoms. Eighty
      nine percent of patients were also diagnosed with another defined
      rheumatic/autoimmune condition. The most frequent autoimmune disease related to
      ASIA syndrome was undifferentiated connective tissue disease (UCTD). ASIA
      syndrome is associated with a high incidence of UCTD and positive anti-nuclear
      antibodies (ANA) test. Clinical and laboratory features differ from the type of
      adjuvant used. These findings may contribute to an increased awareness of ASIA
      syndrome and help physicians to identify patients at a greater risk of autoimmune
      diseases following the exposure to vaccines and other adjuvants. The ASIA
      syndrome registry provides a useful tool to systematize this rare condition.

PMID- 28741090
TI  - Direct comparison of tadalafil with sildenafil for the treatment of erectile
      dysfunction: a systematic review and meta-analysis.
AB  - AIMS: Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and
      sildenafil are the two most common phosphodiesterase 5 inhibitors used to treat
      ED. This systematic review and meta-analysis were conducted to directly compare
      tadalafil with sildenafil for the treatment of ED. METHODS: We designed a
      strategy for searching the PubMed, Embase, EBSCO, Web of Science and Cochrane
      library databases; the reference lists of the retrieved studies were also
      investigated. A literature review was performed to identify all published
      randomized or non-randomized controlled trials that compared tadalafil with
      sildenafil for the treatment of ED and to assess the quality of the studies. Two
      investigators independently and blindly screened the studies for inclusion. The
      meta-analysis was performed using RevMan 5.0. RESULTS: A total of 16 trials that
      compared tadalafil with sildenafil for the treatment of ED were included in the
      meta-analysis. In the meta-analysis, tadalafil and sildenafil appeared to have
      similar efficacies and overall adverse event rates. However, compared with
      sildenafil, tadalafil significantly improved psychological outcomes. Furthermore,
      the patients and their partners preferred tadalafil over sildenafil, and no
      significant difference was found in the adherence and persistence rates between
      tadalafil and sildenafil. Additionally, the myalgia and back pain rates were
      higher and the flushing rate was lower with tadalafil than with sildenafil.
      CONCLUSION: Tadalafil shares a similar efficacy and safety with sildenafil and
      significantly improves patients' sexual confidence. Furthermore, patients and
      their partners prefer tadalafil to sildenafil. Hence, tadalafil may be a better
      choice for ED treatment.

PMID- 28741091
TI  - Hospitalized Patients' Responses to Offers of Prayer.
AB  - Most Americans pray; many pray about their health. When they are hospitalized,
      however, do patients want an offer of prayer from a healthcare provider? This
      project allowed for the measurement of hospitalized patient's responses to
      massage therapists' offers of a colloquial prayer after a massage. After the
      intervention, 78 patients completed questionnaires that elicited quantitative
      data that were analyzed using uni- and bivariate statistical analyses. In this
      sample, 88% accepted the offer of prayer, 85% found it helpful, and 51% wanted
      prayer daily. Patients may welcome prayer, as long as the clinician shows
      "genuine kindness and respect."

PMID- 28741092
TI  - A potent indolylquinoline alleviates growth of human lung cancer cell
      tumorspheres.
AB  - To fight cancer at its roots by targeting cancer stem cells is a promising
      approach for therapy. Previously, an indolylquinoline derivative, 3-((7-ethyl-1H
      indol-3-yl)-methyl)-2-methylquinoline (EMMQ), was reported effectively inhibiting
      the growth of lung cancer cells through impairment of cellular mitochondria
      functions. To address more on drug efficiency, the study further exploited if
      EMMQ can impede the propagation of tumorspheres stemmed from non-small cell lung
      cancer cells. EMMQ inhibited proliferation of spheroids in culture. In animal
      models, administration of the drug attenuated the spheroid tumorigenicity. The
      activated apoptosis alleviated growth of xenograft tumors in immune-deficient
      mice as established by the enriched tumorspheres. More evidence suggested that
      the reduced stemness of the spheroid tumors is attributed to apoptotic death. The
      findings supported that EMMQ is an eligible approach to eradicate the minor but
      tumorigenic lung cancer tumorspheres.

PMID- 28741093
TI  - Fetal Right Ventricular Prominence: Associated Postnatal Abnormalities and
      Coarctation Clinical Prediction Tool.
AB  - Fetal right ventricular (RV) prominence is a known indicator of possible left
      sided structural heart disease with a low positive predictive value for aortic
      coarctation. There is a paucity of data on identifying which fetuses with RV
      prominence will have postnatal arch obstruction. Our study objectives were to
      create a clinical prediction tool for coarctation and to describe the diagnostic
      outcomes of our cohort with fetal RV prominence. We performed a retrospective
      review of patients referred with fetal RV prominence from January 2009 to October
      2015. Recorded fetal echocardiographic variables included gestational age,
      semilunar and atrioventricular valve dimensions, left and right ventricular mid
      cavitary dimensions, foramen ovale and aortic arch flow direction, and isthmal
      diameter. Postnatal cardiac and non-cardiac diagnoses were documented. We
      performed descriptive analysis for postnatal outcomes and classification tree
      analysis to create a clinical prediction tool. Eighty-eight patients were
      reviewed; 58 (66%) had abnormal postnatal echocardiograms, 45 (51%) had left
      sided lesions, including 26 (30%) with coarctation, and 6 (7%) had pulmonary
      hypertension. Our clinical prediction tool employs gestational age, RV mid
      cavitary dimension z-score, and isthmal diameter z-score to predict coarctation
      with 85% accuracy, 95% confidence interval [75.3, 92.4%]. Our model correctly
      classified 45/54 non-coarctation and 19/21 coarctation cases, with 90%
      sensitivity and 83% specificity. Developing an accurate prediction tool for
      coarctation in cases of fetal RV prominence is an important first step in
      improving our management of these challenging cases.

PMID- 28741094
TI  - Systolic Function of Right Ventricular Outflow Tract is a Better Predictor to
      Exercise Performance After Pulmonary Valve Replacement in Tetralogy of Fallot.
AB  - Debate on the proper timing of pulmonary valve replacement (PVR) after repair of
      tetralogy of Fallot is still continuing. We aim to clarify how the different
      components of right ventricle (RV) changed with relieved volume overload in the
      remodeling process after pulmonary valve replacement and gain a clear idea of the
      relationship between different right ventricle components function and exercise
      capacity after PVR in these patients. The medical records and results of cardiac
      magnetic resonance imaging and cardiopulmonary exercise testing of 25 consecutive
      eligible patients were reviewed. End-diastolic, end-systolic, and ejection
      fraction (EF) were determined for the total RV and its components before and
      after PVR. There was a marked increase in EF for the outlet after PVR (39.5 +/-
      11.4 vs. 45.6 +/- 12.7, P = 0.04); however, EF and volume change for the other
      components showed no significant difference. Peak oxygen consumption (VO2)
      correlated better with the RV outflow tract EF than with the EF of other
      components of the RV or the global EF (r = 0.382, P = 0.018), and the time
      interval between initial repair and PVR showed a significant correlation with
      peak VO2 (r = -0.339, P = 0.037). Multivariate analysis showed the RV outflow
      tract EF to be the only independent predictor of exercise capacity (beta = 0.479;
      P = 0.046). The systolic function of the RV outflow tract could be a reliable
      determinant of intrinsic RV performance in repaired TOF (rTOF) patients and a
      promising parameter for deciding timing of pulmonary valve replacement so as to
      achieve the best possible exercise capacity in repaired TOF patients.

PMID- 28741095
TI  - Phenotype microarray analysis of the AdeRS two-component system in Acinetobacter
      baumannii.
AB  - Acinetobacter baumannii is a nosocomial pathogen capable of resistance to
      multiple antimicrobials. The AdeRS two-component system (TCS) is associated with
      antimicrobial resistance by controlling the AdeABC efflux pump. To elucidate
      modulation by AdeRS, we made an A. baumannii mutant lacking the AdeRS TCS and
      characterized it using phenotype microarray (PM) analysis. After disrupting the
      adeRS operon, lower expression of AdeABC efflux pump was observed in the mutant
      strain. PM analysis showed that the AdeRS deletion strain and parental strain
      presented different tolerances to 91 compounds. Tolerance to 54 of the 91
      compounds could be restored by complementing the AdeRS deleted strain with a
      plasmid carrying the adeRS gene. Compared to the parental strain, the AdeRS
      deletion strain was more sensitive to various inhibitors that target on-protein
      synthesis and function of cell membrane permeability. Tolerance to phleomycin of
      the AdeRS deletion strain reduced greatly and was further confirmed with minimum
      inhibitory concentration (MIC) determination and spot assay. The efflux pump
      inhibitor, NMP, could reduce phleomycin MIC four-fold at least for 29 (34.8%) of
      81 tigecycline-resistant extensively drug-resistant A. baumannii (TGC-resistant
      XDRAB) clinical isolates. Our results suggested that the AdeRS TCS of A.
      baumannii was important for both elimination of antibiotics and tolerance to
      particular compounds.

PMID- 28741096
TI  - Reproducible measurement of vancomycin MICs within the susceptible range in
      Staphylococcus aureus by a broth microdilution method with a "quasi-continuum"
      gradient of antibiotic concentrations.
AB  - The availability of reproducible broth microdilution (BMD) methods including
      inter log2 antibiotic dilutions for measuring Staphylococcus aureus (SA)
      vancomycin minimum inhibitory concentrations (MICs) within the susceptible range
      is needed to elucidate the impact of vancomycin MICs on clinical outcomes of
      invasive SA infections. Here, we report on the development of a very precise BMD
      method that incorporates the following incremental antibiotic concentrations:
      0.50, 0.62, 0.75, 0.87, 1.0, 1.25, 1.40, 1.50, 1.60, 1.75, and 2.0 MUg/mL. The
      intra- and inter-assay coefficients of variation of this method were around 20%.
      The mean of the differences in MIC values for all isolates obtained across two
      independent runs performed at one center was 0.04 MUg/mL [95% confidence interval
      (CI), 0.011-0.07 MUg/mL] and that for ten isolates measured at two different
      centers was 0.04 MUg/mL (95% CI, 0-13 MUg/mL). Vancomycin MIC values differed by
      less than 0.1 MUg/mL between runs for most isolates. Storage of isolates at -20 
      degrees C for up to 3 months had no impact on the vancomycin MIC values. The mean
      vancomycin MIC values obtained by the Etest using a standard inoculum (0.5
      McFarland) were significantly higher (p <= 0.001) than those measured by BMD and
      the MIC values measured by the two methods correlated poorly (Rho, 0.319; p =
      0.148). Nevertheless, the mean MIC values measured by the Etest using lower
      inocula (107 or 106 CFU/mL) and those measured by BMD were comparable and
      correlated significantly (p = 0.004 for 107 CFU/mL and p = 0.029 for 106 CFU/mL).

PMID- 28741097
TI  - Distribution and phylogenetic analysis of Blastocystis sp. subtypes isolated from
      IBD patients and healthy individuals in Iran.
AB  - Blastocystis is a single-celled intestinal parasite commonly found in humans and
      a broad range of animals all over the world. In humans, its role in health and
      disease remains unsettled. The aim of our study was to investigate the
      distribution of Blastocystis and Blastocystis subtypes (ST) in patients with
      inflammatory bowel disease (IBD) and control subjects. A total of 71 stool
      samples were collected from IBD patients, 69 and 2 of whom had ulcerative colitis
      (UC) and Crohn's Disease (CD), respectively. Moreover, 166 stool samples from
      healthy subjects were included as control samples. All stool samples were
      cultivated, and 550-bp fragments of the small subunit ribosomal RNA gene was
      amplified from Blastocystis-positive cultures. All PCR-positive samples were
      sequenced. Blastocystis was observed in 9 (12.67%) and 35 (21.1%) IBD patients
      and healthy controls, respectively. There was no statistically significant
      correlation between IBD and presence of Blastocystis (P = 0.147). There was a
      statistically significant correlation between age and Blastocystis colonization
      in the IBD group (P < 0.05), but not among healthy controls. No significant
      correlation between gender and colonization was observed. ST1 and ST3 were
      obtained from 1 (12.5%) and 7 (87.5%) IBD patients, respectively, while in the
      healthy control group, subtypes 1, 2, and 3 were found in 14 (40%), 12 (34.28%),
      and 9 (25.72%), respectively. Phylogenetic analysis showed no variation in the
      distribution of subtypes nor intra-subtype genetic diversity between samples
      acquired from IBD patients and healthy controls. This study showed a trend
      towards a lower prevalence of Blastocystis in IBD patients than in control
      subjects. ST3 sequences isolated from IBD patients and control individuals did
      not appear to differ genetically.

PMID- 28741098
TI  - Regulation of paclitaxel activity by microtubule-associated proteins in cancer
      chemotherapy.
AB  - Microtubules, highly dynamic components of the cytoskeleton, participate in
      diverse cellular activities such as mitosis, cell migration, and intracellular
      trafficking. Dysregulation of microtubule dynamics contributes to the development
      of serious diseases, including cancer. The dynamic properties and functions of
      microtubule network are regulated by microtubule-associated proteins. Paclitaxel,
      an anti-microtubule agent of the taxane family, has shown a success in clinical
      treatment of many cancer patients. However, the variable response activity of
      patients and acquired resistance to paclitaxel limit the clinical use of the
      drug. Accumulating studies show that microtubule-associated proteins can regulate
      paclitaxel sensitivity in a wide range of cancer types. In this review, we will
      describe the roles of various microtubule-associated proteins in the regulation
      of paclitaxel in cancers. Particularly, we will focus on the modulation of
      centrosomal proteins in paclitaxel resistance. Improved understandings of how
      these proteins act might predict treatment responses and provide insights into
      more rational chemotherapeutic regimens in clinical practice.

PMID- 28741099
TI  - Spatial specificity of tactile enhancement during reaching.
AB  - Tactile signals on a hand that serves as movement goal are enhanced during
      movement planning and execution. Here, we examined how spatially specific tactile
      enhancement is when humans reach to their own static hand. Participants
      discriminated two brief and simultaneously presented tactile stimuli: a
      comparison stimulus on the left thumb or little finger from a reference stimulus
      on the sternum. Tactile stimuli were presented either during right-hand reaching
      towards the left thumb or little finger or while holding both hands still
      (baseline). Consistent with our previous findings, stimuli on the left hand were
      perceived stronger during movement than baseline. However, tactile enhancement
      was not stronger when the stimuli were presented on the digit that served as
      reach target, thus the perception across the whole hand was uniformly enhanced.
      In experiment 2, we also presented stimuli on the upper arm in half of the trials
      to reduce the expectation of the stimulus location. Tactile stimuli on the target
      hand, but not on the upper arm, were generally enhanced, supporting the idea of a
      spatial gradient of tactile enhancement. Overall, our findings argue for low
      spatial specificity of tactile enhancement at movement-relevant body parts, here
      the target hand.

PMID- 28741100
TI  - Training and the attentional blink: Raising the ceiling does not remove the
      limits.
AB  - The attentional blink (AB) is a widely studied deficit in reporting the second of
      two sequentially presented targets when they occur within 500 milliseconds. The
      AB often is interpreted to index a structural limit in sequential visual
      processing. However, this interpretation is challenged by reports that the
      deficit can be reduced with several hundred trials of specific training (Braun in
      Nature, 393(6684), 424-425, 1998; Choi et al. in Proceedings of the National
      Academy of Sciences, 109(30), 12242-12247, 2012; Taatgen et al. in Cognitive
      Psychology, 59(1), 1-29, 2009) and other reports that some individuals experience
      very little or no deficit, even without specific training (Martens et al. in
      Journal of Cognitive Neuroscience, 18(9), 1423-1438, 2006). Yet neither of these
      claims has been studied when the artifact of ceiling effects has been removed. We
      sent a small number of participants (n = 5) home to practice an AB task on their
      mobile phones for 3,000-6,000 trials (Experiment 1) and trained a much larger
      number of participants (n = 48) in a similar way for 1,200-1,800 trials
      (Experiment 2). Both experiments used adaptive procedures to equate task
      difficulty throughout training to keep second-target accuracy below ceiling
      levels. The results showed strong training effects on the rate of processing
      sequential information. Despite this, there were (a) robust AB effects after
      training for most participants, (b) no benefit for training on difficult versus
      easy target tasks, and (c) substantial correlations between the magnitude of the
      AB before and after extensive training. These findings support the interpretation
      that the AB is an index of a structural limit in the ability to consciously
      process rapid visual sequences.

PMID- 28741101
TI  - Bundled Payments in Total Joint Replacement: Keeping Our Care Affordable and High
      in Quality.
AB  - PURPOSE OF REVIEW: The purpose of this review was to evaluate the literature
      regarding bundle payment reimbursement models for total joint arthroplasty (TJA).
      RECENT FINDINGS: From an economic standpoint, TJA are cost-effective, but they
      represent a substantial expense to the Centers for Medicare & Medicaid Services
      (CMS). Historically, fee-for-service payment models resulted in highly variable
      cost and quality. CMS introduced Bundled Payments for Care Improvement (BPCI) in
      2012 and subsequently the Comprehensive Care for Joint Replacement (CJR)
      reimbursement model in 2016 to improve the value of TJA from the perspectives of
      both CMS and patients, by improving quality via cost control. Early results of
      bundled payments are promising, but preserving access to care for patients with
      high comorbidity burdens and those requiring more complex care is a lingering
      concern. Hospitals, regardless of current participation in bundled payments,
      should develop care pathways for TJA to maximize efficiency and patient safety.

PMID- 28741102
TI  - The Range of Neurological Complications in Chikungunya Fever.
AB  - BACKGROUND: Chikungunya fever is a globally spreading mosquito-borne disease that
      shows an unexpected neurovirulence. Even though the neurological complications
      have been a major cause of intensive care unit admission and death, to date,
      there is no systematic analysis of their spectrum available. OBJECTIVE: To review
      evidence of neurological manifestations in Chikungunya fever and map their
      epidemiology, clinical spectrum, pathomechanisms, diagnostics, therapies and
      outcomes. METHODS: Case report and systematic review of the literature followed
      established guidelines. All cases found were assessed using a 5-step clinical
      diagnostic algorithm assigning categories A-C, category A representing the
      highest level of quality. Only A and B cases were considered for further
      analysis. After general analysis, cases were clustered according to geospatial
      criteria for subgroup analysis. RESULTS: Thirty-six of 1196 studies were
      included, yielding 130 cases. Nine were ranked as category A (diagnosis of Neuro
      Chikungunya probable), 55 as B (plausible), and 51 as C (disputable). In 15
      cases, alternative diagnoses were more likely. Patient age distribution was
      bimodal with a mean of 49 years and a second peak in infants. Fifty percent of
      the cases occurred in patients <45 years with no reported comorbidity. Frequent
      diagnoses were encephalitis, optic neuropathy, neuroretinitis, and Guillain-Barre
      syndrome. Neurologic conditions showing characteristics of a direct viral
      pathomechanism showed a peak in infants and a second one in elder patients, and
      complications and neurologic sequelae were more frequent in these groups.
      Autoimmune-mediated conditions appeared mainly in patients over 20 years and
      tended to show longer latencies and better outcomes. Geospatial subgrouping of
      case reports from either India or Reunion revealed diverging phenotypic trends
      (Reunion: 88% direct viral vs. India: 81% autoimmune). CONCLUSIONS: Direct viral
      forms of Neuro-Chikungunya seem to occur particularly in infants and elderly
      patients, while autoimmune forms have to be also considered in middle-aged,
      previously healthy patients, especially after an asymptomatic interval. This
      knowledge will help to identify future Neuro-Chikungunya cases and to improve
      outcome especially in autoimmune-mediated conditions. The genetics of Chikungunya
      virus might play a key role in determining the course of neuropathogenesis. With
      further research, this could prove diagnostically significant.

PMID- 28741103
TI  - The significance of biomarkers such as FABP4 in gestational diabetes mellitus and
      the importance of rigorous peer review.

PMID- 28741104
TI  - A Mathematical Model for the Macrophage Response to Respiratory Viral Infection
      in Normal and Asthmatic Conditions.
AB  - Respiratory viral infections are common in the general population and one of the
      most important causes of asthma aggravation and exacerbation. Despite many
      studies, it is not well understood how viral infections cause more severe
      symptoms and exacerbations in asthmatics. We develop a mathematical model of two
      types of macrophages that play complementary roles in fighting viral infection:
      classically [Formula: see text]-[Formula: see text] and alternatively activated
      macrophages [Formula: see text]-[Formula: see text]. [Formula: see text]
      [Formula: see text] destroy infected cells and tissues to remove viruses, while
      [Formula: see text]-[Formula: see text] repair damaged tissues. We show that a
      higher viral load or longer duration of infection provokes a stronger immune
      response from the macrophage system. By adjusting the parameters, we model the
      differences in response to respiratory viral infection in normal and asthmatic
      subjects and show how this skews the system toward a response that generates more
      severe symptoms in asthmatic patients.

PMID- 28741105
TI  - Transmission Fitness in Co-colonization and the Persistence of Bacterial
      Pathogens.
AB  - Humans are often colonized by polymorphic bacteria such as Streptococcus
      pneumoniae, Bordetella pertussis, Staphylococcus Aureus, and Haemophilus
      influenzae. Two co-colonizing pathogen clones may interact with each other upon
      host entry and during within-host dynamics, ranging from competition to
      facilitation. Here we examine the significance of these exploitation strategies
      for bacterial spread and persistence in host populations. We model SIS
      epidemiological dynamics to capture the global behavior of such multi-strain
      systems, focusing on different parameters of single and dual colonization. We
      analyze the impact of heterogeneity in clearance and transmission rates of single
      and dual colonization and find the criteria under which these asymmetries enhance
      endemic persistence. We obtain a backward bifurcation near [Formula: see text] if
      the reproductive value of the parasite in dually infected hosts is sufficiently
      higher than that in singly infected ones. In such cases, the parasite is able to
      persist even in sub-threshold conditions, and reducing the basic reproduction
      number below 1 would be insufficient for elimination. The fitness superiority in
      co-colonized hosts can be attained by lowering net parasite clearance rate
      ([Formula: see text]), by increasing transmission rate ([Formula: see text]), or
      both, and coupling between these traits critically constrains opportunities of
      pathogen survival in the [Formula: see text] regime. Finally, using an adaptive
      dynamics approach, we verify that despite their importance for sub-threshold
      endemicity, traits expressed exclusively in coinfection should generally evolve
      independently of single infection traits. In particular, for [Formula: see text]
      a saturating parabolic or hyperbolic function of [Formula: see text], co
      colonization traits evolve to an intermediate optimum (evolutionarily stable
      strategy, ESS), determined only by host lifespan and the trade-off parameters
      linking [Formula: see text] and [Formula: see text]. Our study invites more
      empirical attention to the dynamics and evolution of parasite life-history traits
      expressed exclusively in coinfection.

PMID- 28741106
TI  - Claustrum sign in a child with refractory status epilepticus after febrile
      illness: why does it happen?

PMID- 28741107
TI  - Development and optimization of a novel sample preparation method cored on
      functionalized nanofibers mat-solid-phase extraction for the simultaneous
      efficient extraction of illegal anionic and cationic dyes in foods.
AB  - A simple and efficient three-step sample preparation method was developed and
      optimized for the simultaneous analysis of illegal anionic and cationic dyes
      (acid orange 7, metanil yellow, auramine-O, and chrysoidine) in food samples. A
      novel solid-phase extraction (SPE) procedure based on nanofibers mat (NFsM) was
      proposed after solvent extraction and freeze-salting out purification. The
      preferred SPE sorbent was selected from five functionalized NFsMs by orthogonal
      experimental design, and the optimization of SPE parameters was achieved through
      response surface methodology (RSM) based on the Box-Behnken design (BBD). Under
      the optimal conditions, the target analytes could be completely adsorbed by
      polypyrrole-functionalized polyacrylonitrile NFsM (PPy/PAN NFsM), and the eluent
      was directly analyzed by high-performance liquid chromatography-diode array
      detection (HPLC-DAD). The limits of detection (LODs) were between 0.002 and 0.01
      mg kg-1, and satisfactory linearity with correlation coefficients (R > 0.99) for
      each dye in all samples was achieved. Compared with the Chinese standard method
      and the published methods, the proposed method was simplified greatly with much
      lower requirement of sorbent (5.0 mg) and organic solvent (2.8 mL) and higher
      sample preparation speed (10 min/sample), while higher recovery (83.6-116.5%) and
      precision (RSDs < 7.1%) were obtained. With this developed method, we have
      successfully detected illegal ionic dyes in three common representative foods:
      yellow croaker, soybean products, and chili seasonings. Graphical abstract
      Schematic representation of the process of the three-step sample preparation.

PMID- 28741108
TI  - Automated clean-up, separation and detection of polycyclic aromatic hydrocarbons
      in particulate matter extracts using a 2D-LC/2D-GC system: a method translation
      from two FIDs to two MS detectors.
AB  - An online two-dimensional (2D) liquid chromatography/2D gas chromatography system
      with two mass-selective detectors has been developed on the basis of a previous
      system with two flame ionization detectors. The method translation involved the
      change of carrier gas from hydrogen to helium, column dimension and detectors.
      The 2D system with two mass-selective detectors was validated with use of
      polycyclic aromatic hydrocarbon (PAH) standards and two standard reference
      materials from air and diesel exhaust. Furthermore, the system was applied to a
      real sample, wood smoke particulates. The PAH values determined correlated well
      with the previous data and those from the National Institute of Standards and
      Technology. The system enhanced the benefits of the previous system, which were
      limited by the low detectability and lack of mass selectivity. This study shows
      an automated 2D system that is valid for PAH analysis of complex environmental
      samples directly from crude extracts. Graphical Abstract Schematic illustration
      showing on-line clean-up, separation and detection using 2D-LC/2D-GC/MS.

PMID- 28741109
TI  - Multi-analyte method development for analysis of brominated flame retardants
      (BFRs) and PBDE metabolites in human serum.
AB  - Commonly, analytical methods measuring brominated flame retardants (BFRs) of
      different chemical polarities in human serum are labor consuming and tedious. Our
      study used acidified diatomaceous earth as solid-phase extraction (SPE) adsorbent
      and defatting material to simultaneously determine the most abundant BFRs and
      their metabolites with different polarities in human serum samples. The analytes
      include three types of commercial BFRs, tetrabromobisphenol A (TBBPA),
      hexabromocyclododecane (HBCD) isomers, and polybrominated biphenyl ethers
      (PBDEs), and dominant hydroxylated BDE (OH-PBDE) and methoxylated BDE (MeO-PBDE)
      metabolites of PBDEs. The sample eluents were sequentially analyzed for PBDEs and
      MeO-BDEs on online gel permeation chromatography/gas chromatography-electron
      capture-negative ionization mass spectrometry (online GPC GC-ECNI-MS) and for
      TBBPA, HBCD, and OH-BDEs on liquid chromatography-tandem mass spectrometry (LC
      MS/MS). Method recoveries were 67-134% with a relative standard deviation (RSD)
      of less than 20%. Method detection limits (MDLs) were 0.30-4.20 pg/mL fresh
      weight (f.w.) for all analytes, except for BDE-209 of 16 pg/mL f.w. The
      methodology was also applied in a pilot study, which analyzed ten real samples
      from healthy donors in China, and the majority of target analytes were detected
      with a detection rate of more than 80%. To our knowledge, it is the first time
      for us in effectively determining BFRs of most types in one aliquot of human
      serum samples. This new analytical method is more specific, sensitive, accurate,
      and time saving for routine biomonitoring of these BFRs and for integrated
      assessment of health risk of BFR exposure.

PMID- 28741110
TI  - Biosensor of alkaline phosphatase based on non-fluorescent FRET of Eu3+-doped
      oxide nanoparticles and phosphorylated peptide labeled with cyanine dye.
AB  - Dephosphorylation of biomolecules under the catalysis of alkaline phosphatase
      (ALP) is a critical physiological process. Abnormal levels of ALP activity have
      been associated with a number of diseases; thus, a simple and sensitive assay of
      ALP activity is highly demanded. Herein, to simulate biological conditions, we
      labeled a hydrosoluble phosphorylated heptapeptide Gly-Pro-Gly-Asn-p-Tyr-Gly-Ala
      (pGA) with aminated heptamethine cyanine dye (Cy) to give a low fluorescent
      labeled peptide Cy-pGA. The synthesized Cy-pGA and Eu3+-doped oxide Y0.6Eu0.4VO4
      nanoparticles (NPs) were employed respectively as acceptor and donor to in situ
      form a non-fluorescent Fluorescence Resonance Energy Transfer (FRET) Cy-pGA-NP
      system, with the help of the strong interaction between Eu3+ ions in the NPs and
      phosphate group in Cy-pGA. The breaking of the FRET system of Cy-pGA-NP was
      triggered by the removal of phosphate group in Cy-pGA catalyzed by ALP and
      resulting in the release of fluorescent Y0.6Eu0.4VO4 NPs. Thus, the formed Cy-pGA
      NP as a sensitive sensor can very well respond to the activity of ALP by
      measuring the time-resolved fluorescent intensity at near-infrared 617 nm (lambda
      ex = 320 nm, delay time 400 MUs). This sensor can not only accurately measure the
      activity of ALP (1-5 mU/mL) in the designed solutions, but it can also be applied
      to detect the activity of ALP in biological samples, such as cell lysate and
      human serum, without the interference of autofluorescent background of biosamples
      and screen ALP inhibitor by a simple mix-and-measure manner. Graphical abstract A
      biosensor of alkaline phosphatase (ALP) based on non-fluorescent FRET of Eu3+
      doped oxide Y0.6Eu0.4VO4 nanoparticles and the phosphorylated heptapeptide
      labeled with cyanine dye (Cy-pGA).

PMID- 28741111
TI  - Label-free fluorescence turn-on aptasensor for prostate-specific antigen sensing
      based on aggregation-induced emission-silica nanospheres.
AB  - Fluorescent light-up probes based on aggregation-induced emission (AIE)-active
      molecules have recently attracted great research interest due to the intelligent
      fluorescence activation mechanism and high sensitivity. In this work, an AIE
      silica nanosphere (SiO2 NP)-based label-free fluorescent aptasensor for the
      sensitive "turn-on" detection of prostate-specific antigen (PSA) is reported for
      the first time. The positively charged amino-functionalized SiO2 NPs were used as
      efficient nanocapturer to electrostatically adsorb single-stranded PSA aptamer
      (PA) to form SiO2 NP-PA nanocomposite as well as adsorb negatively charged
      tetraphenylethylene derivative 3 (TPE3) to form AIE-SiO2 NP nanocomposite. The
      binding of the aptamer to the target PSA could induce a rigid aptamer
      conformation, resulting in the release of the PA away from the surface of SiO2
      NPs. This made the AIE molecules TPE3 aggregate on the SiO2 NP surface and emit
      high fluorescence. With the advantages of simple design and rapid responses, the
      proposed aptasensor showed high sensitivity and selectivity for PSA with a
      detection limit of 0.5 ng/mL. The aptasensor was further applied in human serum
      samples with satisfactory results. Given its versatility, high selectivity, and
      sensitivity, the proposed method could be extended to other targets by varying
      the recognition probes. Graphical abstract An AIE-SiO2 NP-based label-free
      fluorescent aptasensor for the sensitive "turn-on" detection of PSA is reported
      for the first time.

PMID- 28741112
TI  - Investigation of naphthofuran moiety as potential dual inhibitor against BACE-1
      and GSK-3beta: molecular dynamics simulations, binding energy, and network
      analysis to identify first-in-class dual inhibitors against Alzheimer's disease.
AB  - BACE-1 and GSK-3beta are potential therapeutic drug targets for Alzheimer's
      disease. Recently, both the targets received attention for designing dual
      inhibitors for Alzheimer's disease. Until now, only two-scaffold triazinone and
      curcumin have been reported as BACE-1 and GSK-3beta dual inhibitors. Docking,
      molecular dynamics, clustering, binding energy, and network analysis of
      triazinone derivatives with BACE-1 and GSK-3beta was performed to get molecular
      insight into the first reported dual inhibitor. Further, we designed and
      evaluated a naphthofuran series for its ability to inhibit BACE-1 and GSK-3beta
      with the computational approaches. Docking study of naphthofuran series showed a
      good binding affinity towards both the targets. Molecular dynamics, binding
      energy, and network analysis were performed to compare their binding with the
      targets and amino acids responsible for binding. Naphthofuran series derivatives
      showed good interaction within the active site residues of both of the targets.
      Hydrogen bond occupancy and binding energy suggested strong binding with the
      targets. Dual-inhibitor binding was mostly governed by the hydrophobic
      interactions for both of the targets. Per residue energy decomposition and
      network analysis identified the key residues involved in the binding and
      inhibiting BACE-1 and GSK-3beta. The results indicated that naphthofuran series
      derivative 11 may be a promising first-in-class dual inhibitor against BACE-1 and
      GSK-3beta. This naphthofuran series may be further explored to design better dual
      inhibitors. Graphical abstract Naphthofuran derivative as a dual inhibitor for
      BACE-1 and GSK-3beta.

PMID- 28741113
TI  - Approaches to prevent bleeding associated with anticoagulants: current status and
      recent developments.
AB  - Anticoagulants are widely used for the prophylaxis and treatment of
      cardiovascular disorders and to prevent blood clotting during surgeries. However,
      the major limitation associated with anticoagulant therapy is bleeding; all the
      current anticoagulants do have a bleeding risk. The propensity to bleed is much
      higher among the elderly population and patients with renal insufficiency.
      Therefore, there is an utmost and urgent clinical need for a highly efficient,
      nontoxic antidote with excellent anticoagulant reversal activity. This will
      significantly improve the safety of anticoagulation therapy. This review
      summarizes the current options and approaches to reverse anticoagulation activity
      of clinically used anticoagulants. We start with an introduction to thrombosis
      and then summarize the details of current clinically available anticoagulants and
      their mechanisms of action and limitations. This is followed by current practices
      in anticoagulant neutralization including the details of the only clinically
      approved unfractionated heparin antidote, protamine; recent advances in the
      development of antidotes against heparin-based drugs; and direct oral
      anticoagulants (DOACs).

PMID- 28741114
TI  - [Fetal autopsies : Relic or still a gold standard?]
AB  - BACKGROUND: Fetal autopsy rates are decreasing in Western countries although post
      mortem examinations render important information for the parents concerning the
      cause of abortion and risk of recurrence in future pregnancies. OBJECTIVE: The
      intention of the presented study was to analyze the development of fetal
      autopsies in Germany during the last decade and to review accessible information
      obtained by fetal autopsy. MATERIAL AND METHODS: Reports of fetal autopsies
      conducted in two German university Institutes of pathology between 2005 and 2014
      were evaluated retrospectively. Demographic data and the correlation between
      clinical diagnoses and autopsy findings were assessed. In addition, differences
      between spontaneous and induced cases of abortion and differences between the
      institutes were also documented. RESULTS: Overall, 428 fetal autopsies were
      performed, whereby the number of autopsies decreased by 24.2% during the study
      period. Of the examined fetuses 29.7% were induced abortions which as expected
      exhibited different malformations compared to cases of spontaneous abortion (p <
      0.001). There was no evidence of a malformation or other cause of death in 27.1%
      of the cases and 95.7% of these abortions occurred spontaneously. A discrepancy
      between clinical and autopsy findings was evident in 6.8% of cases and 3.5% of
      the autopsy examinations revealed at least one additional malformation compared
      to the prenatal clinical data. CONCLUSION: Despite improvements in prenatal
      diagnostics, fetal autopsies remain an important diagnostic tool even today
      contributing additional information in a considerable number of cases potentially
      revising clinical diagnoses.

PMID- 28741115
TI  - The DTL ERG electrode comes in different shapes and sizes: Are they all good?
AB  - PURPOSE: Although the DTL fiber electrode has been in use in the ERG field for
      more than four decades, its composition was never clearly defined. We compared
      five different types of conductive (DTL type) yarn (differing in terms of mass,
      number of filaments, and crimping degree) in order to determine whether we could
      identify one that would be better suited for the recording of ERGs. METHODS:
      Photopic flash ERGs were recorded from five subjects using the following DTL
      electrodes: 27/7, 22/1, 11/1, 11/1*2, and 22/1*2. Data analysis included
      amplitude and peak time measurements of the a- and b-waves in the time domain
      (TD) as well as measurements of specific frequency descriptors of the ERG
      waveform in the time-frequency domain using the discrete wavelet transform (DWT)
      approach. The degree of comfortableness was also assessed in 12 subjects with two
      surveys (Likert 5-point and the ranking scale). RESULTS: Comparisons of TD and
      DWT parameters did not permit to identify the best DTL electrode, all yielding
      comparable measures. There was a slight trend for the largest electrode (22/1*2)
      to yield the largest response, but this was at the expense of comfort, the 22/1*2
      electrode being rated as the least comfortable. CONCLUSIONS: Given the minimal
      impact the different electrodes had on the amplitude of the signal, we believe
      that comfort should dictate our choice. It would appear from our results that use
      of a multifilament electrode is the best choice since one can get an electrode
      whose size is optimized for the recording of large responses while minimizing the
      foreign-body sensation due to the small size of each of the filaments that
      compose this multifilament electrode.

PMID- 28741116
TI  - Application of Multivariate Curve Resolution-Alternate Least Square Technique on
      Extracting Pure Spectral Components from Multiple Emitting Systems: a Case Study.
AB  - Multiple emitting components in a fluorophoric system often produce complicated
      emission spectra. Extracting the individual spectral information from the
      composite spectra is important in order to comprehend the photophysical processes
      occurring in the multifluorophoric systems. Although the combination of Principal
      Component Analysis and Multivariate Curve Resolution-Alternate Least Square
      (PCA/MCR-ALS) technique is a well-known approach for curve deconvolution, its
      applicability in the spectral deconvolution of vibronically and electronically
      mixed up emitting systems as well as systems merged up with multiple electronic
      bands without a priori knowledge of the individual emitting species, is not
      properly studied. The present work highlights the strength of PCA/MCR-ALS in
      retrieving pure spectral information from the set of complex spectra arising out
      of the regular variation of causative factors that result in the variation of
      spectral composition. The retrieval of the emission bands utilizing the PCA/MCR
      ALS technique has been made without having a priori information of the emitting
      species present in the multifluorophoric systems and the resolved spectra
      correspond well with the fluorescence spectra of the individual chemical species.
      The common curve fitting methods such as Gaussian and Lorentzian techniques have
      been found to be unsuccessful in providing meaningful photophysical information
      through the retrieved spectra. A comparative study of the curve fitting
      techniques MCR-ALS, Gaussian and Lorentzian in a set of complicated emission
      spectra of (i) pyrene and its excimer, (ii) pyrene and its excimer in presence of
      benzo[a]pyrene, and (iii) fisetin in bile salt medium is presented herein in
      details.

PMID- 28741117
TI  - Induction of alpha-methylacyl-CoA racemase by miR-138 via up-regulation of beta
      catenin in prostate cancer cells.
AB  - PURPOSE: Alpha-methylacyl-CoA racemase (AMACR) is highly overexpressed in
      prostate cancer (PCa) and its transcriptional regulators include various
      transcription factors and CTNNB1/beta-catenin. Our previous findings suggested a
      post-transcriptional regulation by the tumor-suppressive microRNA miR-138 in PCa.
      Thus, the aim of this study was to demonstrate the direct interaction of miR-138
      with the 3'-UTR of AMACR. Furthermore, the influence of miR-138 on the expression
      of AMACR and selected AMACR regulators was investigated in PCa cells. METHODS:
      Using DU-145, PC-3, and LNCaP PCa cells, the effect of exogenous miR-138 on AMACR
      and selected AMACR regulators was determined by quantitative PCR and Western
      blot. Luciferase reporter assays were used to verify target and promoter
      interaction. RESULTS: Using a luciferase reporter assay a direct interaction of
      miR-138 with the AMACR-3'-UTR was confirmed. Surprisingly, AMACR expression was
      up-regulated by up to 125% by exogenous miR-138 in PCa cells. The lack of any miR
      138 binding sites within the AMACR promoter suggested an indirect mechanism of up
      regulation. Therefore, the effect of miR-138 on selected AMACR regulators
      including CTNNB1/beta-catenin, RELA, SMAD4, SP1, and TCF4 was evaluated. MiR-138
      solely evoked an up-regulation of CTNNB1 mRNA expression and beta-catenin protein
      levels by up to 75%. Further in silico analysis revealed a binding site for miR
      138 within the CTNNB1 promoter. MiR-138 could enhance the activity of the CTNNB1
      promoter, which in turn could contribute to the observed AMACR up-regulation.
      CONCLUSIONS: The present findings suggest that miR-138 can indirectly up-regulate
      AMACR via transcriptional induction of CTNNB1, at least in vitro in PCa cells.

PMID- 28741118
TI  - Strategies to decrease injection site pain in botulinum toxin therapy.
AB  - Botulinum toxin is now used for numerous indications including dystonias,
      spasticity, cerebral palsy, hyperhidrosis, cosmetics and chronic migraine. It has
      to be injected into its target tissues thus causing injection site pain. We
      wanted to compare the efficacy of various analgesic interventions suggested for
      reduction of injection site pain. In 13 healthy controls, pain thresholds in the
      fingertips II and III bilaterally were determined by the Mechanical Pain
      Threshold Test and the Repetitive Pain Stimulation Test at baseline and under
      nitrous oxide/oxygen, ice spray, local anaesthetic cream and forearm ischaemia.
      All interventions studied produce statistically significant and robust elevations
      of the pain threshold in both tests. Nitrous oxide/oxygen had stronger effects
      than the other interventions, although this superiority was statistically
      significant only in the Repetitive Pain Stimulation Test and not against ice
      spray. Also considering duration, localisation and penetration depth of analgesic
      effects, hyperhidrosis treatment may benefit from nitrous oxide/oxygen, ice spray
      and local anaesthetic cream. In palmar hyperhidrosis, forearm ischaemia is
      possible and also reduces botulinum toxin washout. Cosmetic indications may also
      benefit from nitrous oxide/oxygen and local anaesthetic cream. For botulinum
      toxin therapy of spasticity, dystonia and tremor, only nitrous oxide/oxygen may
      offer intramuscular analgesic effect. Its systemic and prolonged effect is also
      an advantage in injections in several body parts. Future studies are necessary to
      test the influence of penetration depth and combinations of analgesic
      interventions.

PMID- 28741119
TI  - Treatable Genetic Metabolic Epilepsies.
AB  - OPINION STATEMENT: In the absence of a culprit epileptogenic lesion,
      pharmacoresistant seizures should prompt the physician to consider potentially
      treatable metabolic epilepsies, especially in the presence of developmental
      delays. Even though the anti-seizure treatment of the epilepsies remains
      symptomatic and usually tailored to an electroclinical phenotype rather than to
      an underlying etiology, a thorough metabolic workup might reveal a disease with
      an etiology-specific treatment. Early diagnosis is essential in the case of
      treatable metabolic epilepsies allowing timely intervention. Despite the advances
      in genetic testing, biochemical testing including cerebrospinal fluid studies are
      still needed to expedite the diagnostic workup and potential therapeutic trials.
      The diagnostician should have a high index of suspicion despite potential
      clinical digressions from seminal publications describing the initial cases, as
      these index patients may represent the most severe form of the condition rather
      than its most common presenting form. The often gratifying developmental outcome
      and seizure control with early treatment calls for a prompt diagnostic
      consideration of treatable metabolic diseases; even though relatively rare or
      potentially only seemingly so.

PMID- 28741120
TI  - CADASIL: Treatment and Management Options.
AB  - OPINION STATEMENT: CADASIL is a life-threatening and disabling disease. Despite
      the progress achieved so far, no therapies able to limit the disease progression
      have been found and only empiric treatments can be employed to relieve the main
      disease symptoms. Further in vivo studies as well as data aggregation and multi
      centre controlled clinical trials are needed to confirm the emerging findings in
      order to identify evidence-based therapies for CADASIL.

PMID- 28741121
TI  - Interaction of Newly Platinum(II) with Tris(2-carboxyethyl)phosphine Complex with
      DNA and Model Lipid Membrane.
AB  - Structural properties of plasmid DNA and model lipid membrane treated with newly
      synthesized platinum(II) complex cis-[PtCl2{P(CH2CH2COOH)3}2] (cis-DTCEP for
      short) were studied and compared with effects of anticancer drug cisplatin, cis
      [Pt(NH3)2Cl2] (cis-DDP for short). Time Correlated Single Photon Counting
      Fluorescence Correlation Spectroscopy (TCSPC-FCS) was employed to study
      interactions between those platinum complexes and DNA. The TCSPC-FCS results
      suggest that bonding of cis-DTCEP derivative to DNA leads to plasmid strain
      realignment towards much more compact structure than in the case of cis-DDP.
      Application of both differential scanning calorimetry and infrared spectroscopy
      to platinum complexes/DPPC showed that cis-DTCEP slightly increases the
      phospholipid's main phase transition temperature resulting in decreased fluidity
      of the model membrane. The newly investigated compound-similarly to cis-DDP
      interacts mainly with the DPPC head group however not only by the means of
      electrostatic forces: this compound probably enters into hydrophilic region of
      the lipid bilayer and forms hydrogen bonds with COO groups of glycerol and PO2-
      group of DPPC.

PMID- 28741122
TI  - Adherence to National Comprehensive Cancer Network Guidelines is Associated with
      Improved Survival for Patients with Stage 2A and Stages 2B and 3 Extremity and
      Superficial Trunk Soft Tissue Sarcoma.
AB  - BACKGROUND: The National Comprehensive Cancer Network (NCCN) has instituted
      treatment guidelines for stage 2A and stages 2B and 3 extremity and superficial
      trunk soft tissue sarcomas (ETSTS). This study examined adherence to the NCCN
      guidelines and factors associated with nonadherent treatment and survival
      outcomes. METHODS: Patients with stage 2A and stages 2B and 3 ETSTS (n = 15,957)
      were categorized as undergoing adherent or nonadherent treatment based on the
      2014 NCCN guidelines. Multivariate logistic regression models were used to
      determine factors associated with nonadherent treatment. Overall survival (OS)
      and disease-specific survival (DSS) were calculated, and Cox models were used to
      generate adjusted survival curves and hazard ratios (HRs). RESULTS: The findings
      showed that 87.2% of the patients with stage 2A disease and 58.3% of the patients
      with stage 2B or 3 disease received adherent treatment. Community treatment
      facilities and uninsured or unknown insurance status were associated with
      nonadherent treatment for both stage groups. Adherent treatment was associated
      with higher 5-year adjusted OS and DSS for stage 2A and stage 2B or 3 patients.
      In Cox models, nonadherent treatment was associated with worse survival for both
      stage 2A disease (HR, 2.31; 95% confidence interval [CI], 2.02-2.63) and stages
      2B and 3 disease (HR, 1.63; 95% CI, 1.53-1.73). Increasing age and non-private
      insurance were associated with poorer outcomes. For stages 2B and 3 disease,
      treatment at a community center and African American race were associated with
      worse survival. CONCLUSIONS: Adherence to NCCN guidelines is excellent for stage
      2A and poor for stages 2B and 3 ETSTS. Adherent treatment was associated with
      improved survival outcomes, highlighting the importance of adherence to NCCN
      guidelines.

PMID- 28741123
TI  - Neoadjuvant Radiotherapy is Associated with R0 Resection and Improved Survival
      for Patients with Extremity Soft Tissue Sarcoma Undergoing Surgery: A National
      Cancer Database Analysis.
AB  - BACKGROUND: Neoadjuvant radiotherapy (RT) is increasingly advocated for the
      management of soft tissue sarcoma (STS). Therefore, this study sought to
      characterize the impact of neoadjuvant RT on rates of R0 resection and overall
      survival (OS) in extremity STS patients undergoing surgery. METHODS: From January
      2003 to December 2012, the study identified patients with a diagnosis of
      extremity STS from the National Cancer Database. After exclusion of patients
      younger than 18 years, not treated by surgery, who had metastases at diagnosis,
      intraoperative RT, and missing or unknown data, 27,969 patients were identified.
      Logistic regression and Cox-proportional hazard analysis were used to compare
      rates of R0 resection among preoperative, postoperative, and no-RT cohorts and to
      determine predictors of R0 resection and OS. RESULTS: The mean age of the
      patients was 59.5 +/- 17.1 years, and 45.9% were female. The median tumor size
      was 10.5 cm. The data showed that 51% of the patients did not receive RT, 11.8%
      received preoperative RT, and 37.2% received postoperative RT. The rates of R0
      resection were 90.1% for the preoperative RT cohort, 74.9% for the postoperative
      RT cohort, and 79.9% for the no-RT cohort (P < 0.001). The independent predictors
      for achievement of R0 resection included academic facility type (odds ratio [OR]
      1.36; 95% confidence interval [CI] 1.20-1.55), histologic subtype, tumor size (OR
      0.99; 95% CI 0.99-0.99), Charlson score (OR 0.92; 95% CI 0.84-0.99), and
      preoperative RT (OR 1.83; 95% CI 1.61-2.07). Both R0 resection and RT (pre- or
      post-operative) were associated with increased OS. CONCLUSIONS: Preoperative RT
      independently predicts higher rates of R0 resection for patients with extremity
      STS undergoing surgical resection. Negative surgical margins and pre- or
      postoperative RT are associated with improved OS.

PMID- 28741124
TI  - Characterization of a low-density lipoprotein receptor, Lrp13, in Chinese tongue
      sole (Cynoglossus semilaevis) and medaka (Oryzias latipes).
AB  - As an important economic marine species cultured in China, Chinese tongue sole
      (Cynoglossus semilaevis) has interested us due to its sexual dimorphism and ZW/ZZ
      sex determination system. In a previous study, dmrt1 was identified as a dosage
      dependent male-determining gene. In the present study, a female-specific
      expressed gene, cse0440, initially annotated as lrp1b-like, was identified from
      chromosome W of C. semilaevis. In view of the differences between cse0440 and
      lrp1b in terms of expression pattern, a phylogenetic analysis containing 85 LRP
      proteins was constructed and provided an evidence to re-annotate cse0440 as
      cseLRP13. In addition, two orthologues of cseLRP13 were separately identified
      from W and Z chromosomes: cseLRP13-W and cseLRP13-Z. The subsequent multiple
      sequence alignment and syntenic arrangements of LRP13 in C. semilaevis, Japanese
      medaka (Oryzias latipes), large yellow croaker (Larimichthys crocea), striped
      bass (Morone saxatilis), white perch (Morone americana) and Fugu rubripes
      (Takifugu rubripes) further supported this re-annotation. RT-PCR and in situ
      hybridization revealed that cselrp13 was exclusively expressed in the oocytes and
      follicles of ovaries. These results suggested that lrp13 may play important roles
      in female reproduction. In future, with the advancement of micromanipulation in
      flatfish, the detailed function of two lrp13 orthologues in C. semilaevis will be
      elucidated.

PMID- 28741125
TI  - Identification of Carboxylate, Phosphate, and Phenoxide Functionalities in
      Deprotonated Molecules Related to Drug Metabolites via Ion-Molecule Reactions
      with water and Diethylhydroxyborane.
AB  - Tandem mass spectrometry based on ion-molecule reactions has emerged as a
      powerful tool for structural elucidation of ionized analytes. However, most
      currently used reagents were designed to react with protonated analytes, making
      them suboptimal for acidic analytes that are preferentially detected in negative
      ion mode. In this work we demonstrate that the phenoxide, carboxylate, and
      phosphate functionalities can be identified in deprotonated molecules by use of a
      combination of two reagents, diethylmethoxyborane (DEMB) and water. A novel
      reagent introduction setup that allowed DEMB and water to be separately
      introduced into the ion trap region of the mass spectrometer was developed to
      facilitate fundamental studies of this reaction. A new reagent,
      diethylhydroxyborane (DEHB), was generated inside the ion trap by hydrolysis of
      DEMB on introduction of water. Most carboxylates and phenoxides formed a DEHB
      adduct, followed by addition of one water molecule and subsequent ethane
      elimination (DEHB adduct +H2O - CH3CH3) as the major product ion. Phenoxides with
      a hydroxy group adjacent to the deprotonation site and phosphates formed a DEHB
      adduct, followed by ethane elimination (DEHB adduct - CH3CH3). Deprotonated
      molecules with strong intramolecular hydrogen bonds or without the aforementioned
      functionalities, including sulfates, were unreactive toward DEHB/H2O. Reaction
      mechanisms were explored via isotope labeling experiments and quantum chemical
      calculations. The mass spectrometry method allowed the differentiation of
      phenoxide-, carboxylate-, phosphate-, and sulfate-containing analytes. Finally,
      it was successfully coupled with high-performance liquid chromatography for the
      analysis of a mixture containing hymecromone, a biliary spasm drug, and its three
      possible metabolites. Graphical Abstract ?.

PMID- 28741126
TI  - An Increase in Dietary Supplement Exposures Reported to US Poison Control
      Centers.
AB  - INTRODUCTION: The objective of this study was to investigate the epidemiology of
      dietary supplement exposures in the USA. METHODS: A retrospective analysis was
      conducted of out-of-hospital dietary supplement exposures reported to the
      National Poison Data System from 2000 through 2012. RESULTS: There were 274,998
      dietary supplement exposures from 2000 through 2012. The annual rate of dietary
      supplement exposures per 100,000 population increased by 46.1% during 2000-2002,
      decreased 8.8% during 2002-2005, and then increased again by 49.3% from 2005 to
      2012. These trends were influenced by the decrease in ma huang exposures starting
      in 2002. Miscellaneous dietary supplements accounted for 43.9% of all exposures,
      followed by botanicals (31.9%), hormonal products (15.1%), and other supplements
      (5.1%). The majority of dietary supplement exposures (70.0%) occurred among
      children younger than 6 years old and were acute (94.0%) and unintentional
      (82.9%). Serious medical outcomes accounted for 4.5% of exposures and most
      (95.0%) occurred among individuals 6 years and older. Ma huang products, yohimbe,
      and energy products were the categories associated with the greatest toxicity.
      CONCLUSIONS: There was an overall increase in the rate of dietary supplement
      exposures from 2000 through 2012. Although the majority of these exposures did
      not require treatment at a health care facility or result in serious medical
      outcomes, exposures to yohimbe and energy products were associated with
      considerable toxicity. Our results demonstrate the success of the FDA ban on ma
      huang products and the need for FDA regulation of yohimbe and energy products in
      the USA.

PMID- 28741127
TI  - Wing morphology, winter ecology, and fecundity selection: evidence for sex
      dependence in barn swallows (Hirundo rustica).
AB  - Variation in wing morphology results from the combination of diverse selection
      pressures. Wing feather morphology within species varies with sex and ontogenetic
      effects, and also with ecological factors. Yet, the direction of causation for
      the wing morphology-ecology association remains to be elucidated. Under the
      'ecology-dependence' hypothesis, wing morphology covaries with ecological
      conditions, because the latter affect feather molt. Alternatively, the 'habitat
      choice' hypothesis posits that individuals with different wing morphology choose
      different habitats because of the habitat-dependent advantages of a specific wing
      morphology. We tested these competing hypotheses in the migratory, aerially
      insectivorous barn swallow (Hirundo rustica). We quantified wing morphology
      (isometric size, pointedness, and convexity) on the same individuals during
      consecutive breeding seasons (i.e., before and after molt in sub-Saharan
      wintering areas) and located wintering areas using light-level geolocators. Wing
      pointedness of females but not males during 1 year negatively correlated with
      vegetation vigor (gauged by the Normalized Difference Vegetation Index; NDVI) in
      the African area where individuals spent the next winter. Partial least-squares
      path modelling showed that the association between wing morphology and NDVI was
      sex-dependent. Conversely, NDVI during wintering did not predict wing morphology
      in the next breeding season. Because wing morphology can have carry-over effects
      on subsequent performance, we investigated selection on wing traits and found
      strong positive fecundity selection on wing size of females. Our results suggest
      that female barn swallows choose their wintering habitat depending on their wing
      morphology. In addition, directional fecundity selection operates on females,
      suggesting sex-dependence of current selection on the flight apparatus.

PMID- 28741128
TI  - Transcriptomic responses of three aphid species to chemical insecticide stress.

PMID- 28741129
TI  - Overexpression of GhPFN2 enhances protection against Verticillium dahliae
      invasion in cotton.
AB  - Growing evidence indicates that actin cytoskeleton is involved in plant innate
      immune responses, but the functional mechanism remains largely unknown. Here, we
      investigated the behavior of a cotton profilin gene (GhPFN2) in response to
      Verticillium dahliae invasion, and evaluated its contribution to plant defense
      against this soil-borne fungal pathogen. GhPFN2 expression was up-regulated when
      cotton root was inoculated with V. dahliae, and the actin architecture was
      reorganized in the infected root cells, with a clear increase in the density of
      filamentous actin and the extent of actin bundling. Compared to the wild type,
      GhPFN2-overexpressing cotton plants showed enhanced protection against V. dahliae
      infection and the actin cytoskeleton organization in root epidermal cells was
      clearly altered, which phenocopied that of the wild-type (WT) root cells
      challenged with V. dahliae. These results provide a solid line of evidence
      showing that actin cytoskeleton reorganization involving GhPFN2 is important for
      defense against V. dahliae infection.

PMID- 28741130
TI  - Epigenetic involvement in etiopathogenesis and implications in treatment of
      systemic lupus erythematous.
AB  - BACKGROUND: Recent researches in the field of genetics have extended our
      knowledge through the discovery of genetic factors associated with autoimmune
      diseases (AID). Genetics by itself, however, cannot elucidate all the
      uncertainties encountered in the etiopathology of AID. On the other hand,
      incomplete harmony in the prevalence of AID in identical twins suggests that non
      genetic factors may play an important role in determining the disease
      susceptibility. Besides, epigenetics, which is defined by changes in gene
      expression without a corresponding change in the DNA sequences, has come in to
      provide new awareness in the disease etiopathology by bridging the genetic and
      epigenetic factors. The recent advances in the field of epigenetics provide a new
      insight into the understanding of the disease mechanisms, development, diagnostic
      and prognostic approaches, as well as the various treatment methods. PURPOSE:
      This review paper aims to present an overview of epigenetic modifications
      involved in the pathogenesis of systemic lupus erythematosus (SLE) and discuss
      their important roles in clinical and pharmacological settings, including novel
      and recent therapeutic applications. RESULTS: Nowadays, it is believed that
      autoimmune diseases, such as SLE, begin when genetically susceptible factors
      associate with environmental triggers. The current therapeutic approaches for SLE
      treatment have been based on treatments with immunosuppressive drugs, which are
      linked to various side effects. It is difficult to develop highly effective
      treatments for SLE patients with minimal or no side effects, mainly due to the
      disease complexity. The breakthrough of pharmacoepigenetics provides a new
      approach to solve this problem. Epigenetic modifications can influence the
      efficacy of drugs by changing the gene expression through modifying chromatin
      remodeling. In this regard, epigenetic studies in SLE are expected to reveal
      novel disease biomarkers and therapeutic targets. CONCLUSIONS: Accumulating
      evidence disclosed that epigenetic dysregulations are engaged in SLE pathogenesis
      and may be exerted as biomarkers to diagnose and as tools to treat these
      patients.

PMID- 28741131
TI  - Meiotic chromosome behavior of the male-fertile allotriploid lily cultivar
      'Cocossa'.
AB  - KEY MESSAGE: Cytological observations of microsporogenesis in the allotriploid
      lily cultivar 'Cocossa' showed that viable pollen production could be attributed
      mainly to disoriented spindles, abnormal cytokinesis, and cytomixis during male
      meiosis. To identify the reasons why the allotriploid lily cultivar 'Cocossa' can
      produce aneuploid and euploid functional male gametes and can be used as the
      paternal parent in lily introgression breeding, we performed a detailed
      investigation of microsporogenesis using the conventional cytological methods.
      The allotriploid not only produced single pollen grains with variable sizes but
      also produced adherent pollen grains. Pollen viability was estimated at 50.1%
      based on staining and 30.8% based on germination. Based on the chromosomal
      analysis of BC2 plants derived from Oriental cultivars (?) crossed with the OOT
      cultivar 'Cocossa' (?), it was concluded that the objective allotriploid
      contributed haploid (x), diploid (2x), and aneuploid chromosome complements.
      Common meiotic abnormalities were observed, indicating the high genetic imbalance
      of this allotriploid. In addition to normally oriented metaphase II spindles
      (linear and perpendicular), abnormal spindles, such as parallel, tripolar, fused,
      and multiple spindles, accounted for 6.21, 6.41, 14.27, and 1.17%, respectively.
      Tripolar and fused spindles resulted in the production of triads and dyads, which
      contributed to unreduced pollen production. Some microsporocytes exhibited
      complete or partial absence of cytokinesis, which led to relatively high
      frequencies of monads, dyads, and triads. Furthermore, the phenomenon of
      cytomixis during microsporogenesis occurred mainly in the first meiotic prophase
      and early development of pollen grains, which we assume is a possible cause of
      unreduced gamete generation. Our study offers a new resource for lily
      introgression breeding.

PMID- 28741132
TI  - Erratum to: Factors Associated with Mood Disorder Diagnosis Among a Population
      Based Cohort of Men and Women Living With and Without HIV in British Columbia
      Between 1998 and 2012.

PMID- 28741133
TI  - African and Caribbean Nurses' Decisions about HIV Testing: A Mixed Methods Study.
AB  - Nurses in Jamaica, Kenya, South Africa, and Uganda are at risk for occupational
      exposure to HIV. Little is known about the experiences and policy supports
      related to nurses having themselves tested for the virus. This article reports a
      mixed-methods study about contextual influences on nurses' decision-making about
      HIV testing. Individual and focus group interviews, as well as a questionnaire on
      workplace polices and quality assurance and a human resource management
      assessment tool provided data. Fear of a positive diagnosis and stigma and lack
      of confidentiality along with gaps in the policy environment contributed to
      indecision about testing. There were significant differences in policy supports
      among countries. Institutional support must be addressed if improvements in HIV
      testing for health care workers are going to be effectively implemented. Future
      work is required to better understand how HRM policies intersect to create
      conditions of perceived vulnerability for HIV positive staff.

PMID- 28741134
TI  - A Cluster Randomised Trial to Determine the Efficacy of the "Feeding Buddies"
      Programme in Improving Exclusive Breastfeeding Rates Among HIV-Infected Women in
      Rural KwaZulu-Natal, South Africa.
AB  - This cluster randomised trial in KwaZulu-Natal South Africa, evaluated the
      implementation of a Feeding Buddies (FB) programme to improve exclusive
      breastfeeding (EBF) amongst human immunodeficiency virus infected mothers. Eight
      clinics were randomly allocated to intervention and control arms respectively.
      Pregnant women attending the prevention of mother-to-child transmission program
      and intending to EBF were enrolled: control (n = 326), intervention (n = 299).
      Intervention mothers selected FBs to support them and they were trained together
      (four sessions). Interviews of mothers occurred prenatally and at post-natal
      visits (day 3, weeks 6, 14 and 22). Breastfeeding results were analysed (Stata)
      as interval-censored time-to-event data, with up to four time intervals per
      mother. EBF rates at the final interview were similar for control and
      intervention groups: 44.68% (105/235) and 42.75% (109/255) respectively (p =
      0.67). In Cox regression analysis better EBF rates were observed in mothers who
      received the appropriate training (p = 0.036), had a community care giver visit
      (p = 0.044), while controlling for other factors. Implementation realities
      reduced the potential effectiveness of the FBs.

PMID- 28741135
TI  - HIV Positive Diagnosis During Pregnancy Increases Risk of IPV Postpartum Among
      Women with No History of IPV in Their Relationship.
AB  - There has been limited study of whether and for whom physical intimate partner
      violence (IPV) is a consequence of an HIV-positive diagnosis. Per the diathesis
      stress model, the consequences of HIV infection may be worse for women with a
      history of IPV. We hypothesize that the positive association between HIV
      diagnosis in pregnancy and postpartum IPV will be exacerbated for women with a
      history of IPV. Data come from a prospective cohort study with 1015 participants
      who completed a baseline antenatal and 9-month postpartum visit. Using logistic
      regression analyses, we found a statistically significant interaction between HIV
      diagnosis, history of IPV and postpartum IPV (AOR: 0.40, 95% CI 0.17-0.96). The
      findings were in the opposite direction as expected: HIV-diagnosis was not
      associated with IPV for women with a history of IPV (AOR: 2.17, 95% CI 1.06,
      4.42). However, HIV-positive women without a history of IPV faced more than two
      times the risk of incident postpartum IPV than HIV-negative women (AOR: 2.17, 95%
      CI 1.06, 4.42). Interventions to reduce incident and ongoing IPV during the
      perinatal period are needed.

PMID- 28741136
TI  - Predictors of Resilience and Posttraumatic Growth Among People Living with HIV: A
      Longitudinal Study.
AB  - This longitudinal study investigated the predictors of HIV-related resilience
      (HR) and posttraumatic growth (PTG) among Spanish-speaking HIV-positive people.
      Perceived past resilience, internalised stigma, and coping strategies were
      hypothesised as possible predictors. Data were collected at two time points from
      119 HIV-positive people. Path analyses with latent variables revealed that half
      of HR 8 months after diagnosis was predicted by rumination, emotional expression,
      positive thinking, internalised stigma, and perceived past resilience. The latter
      three, along with isolation, self-blame, thinking avoidance, and help seeking
      predicted some PTG dimensions 8 months after diagnosis. The results highlight the
      importance of internalised stigma associated with HIV infection and of the
      differential use of coping strategies, and point to the need for clinicians and
      policy makers to implement stigma reduction and appropriate coping strategies
      interventions.

PMID- 28741137
TI  - Protection of the Proximal Articular Cartilage During Percutaneous Thermal
      Ablation of Acetabular Metastasis Using Temperature Monitoring.
AB  - OBJECTIVE: To review our initial experience in acetabular cartilage protection
      from thermal injury with temperature monitoring during percutaneous image-guided
      tumor thermal ablation. MATERIALS AND METHODS: Between June 2015 and December
      2016, three consecutive oncologic patients (mean age 58 years; range 48-67 years)
      with acetabular bone metastasis underwent percutaneous image-guided thermal
      ablation procedures along with hip joint cartilage thermal monitoring. Due to the
      close proximity of the metastatic lesion to the acetabular articular cartilage, a
      thermosensor device was placed under CT and fluoroscopic guidance near the
      acetabular roof and next to the ablation zone in order to monitor the local
      temperature around the articular cartilage. Stand-alone thermal ablation (n = 1)
      and combined thermal ablation with cementoplasty (n = 2) were performed to
      optimize local palliation or disease control. Clinical and radiological outcomes
      at follow-up were assessed. RESULTS: Three acetabular metastatic lesions were
      treated with thermal ablation, and temperature monitoring of the acetabular
      articular cartilage was conducted during the ablation procedure. Mean size of
      lesions was 1.6 cm (range 1.5-2 cm). Technical success was achieved in all cases
      (100%) without any immediate complications. No hip cartilage damage occurred
      clinically and radiologically. Good palliation and local disease control were
      achieved in two cases, and in the other case, there was local recurrence and
      distant progression of hip metastatic disease after 7 months of follow-up.
      CONCLUSION: Temperature monitoring of the articular cartilage during percutaneous
      image-guided thermal ablation appears technically feasible with good short-term
      efficacy in a complex patient subset. Further studies are warranted to confirm
      these promising initial results.

PMID- 28741138
TI  - Trans-splenic Access for Portal Venous Interventions in Children: Do Benefits
      Outweigh Risks?
AB  - BACKGROUND: The primary concern of trans-splenic access for portal interventions
      is the risk of life-threatening intraperitoneal bleeding. OBJECTIVE: To review
      the clinical indications and efficacy and evaluate the risk factors for
      intraperitoneal bleeding during trans-splenic portal interventions in children.
      MATERIALS AND METHODS: A retrospective review of consecutive patients who
      underwent trans-splenic portal interventions at a tertiary care pediatric
      institution between March 2011 and April 2017 was performed. Forty-four
      procedures were performed in 30 children with a median age of 5 (0.3-18) years.
      Clinical indications, technical success, procedural success, and incidence of
      complications were recorded. Potential risk factors for intraperitoneal bleeding
      were evaluated using Wilcoxon rank and Fisher's exact tests. RESULTS: Trans
      splenic access was 100% successful. In 35/44 (79%) procedures, the subsequent
      intervention was successful including recanalization of post-transplant portal
      vein occlusion in 10/13, embolization of bleeding Roux limb varices in 8/8,
      recanalization of chronic portal vein thrombosis in native liver in 7/13,
      splenoportography and manometry in 6/6, and occlusion of portosystemic shunts in
      4/4 procedures. Intraperitoneal bleeding occurred during 12/44 (27%) procedures
      and was managed with analgesics, blood transfusion, and peritoneal drainage
      without the need for splenectomy or splenic artery embolization. Statistically
      significant correlation of bleeding was found with intraprocedural
      anticoagulation, but not with patient age, weight, platelet count, INR, ascites,
      splenic length, splenic venous pressure, vascular sheath size, or tract
      embolization technique. CONCLUSION: Trans-splenic access is a useful technique
      for successful pediatric portal interventions. Although it entails a substantial
      risk of intraperitoneal bleeding, this can be managed conservatively.

PMID- 28741139
TI  - Characterization of a Liquid Crystal System for Sustained Release of a Peptide
      BMS-686117.
AB  - Liquid crystal lipid-based formulations are an effective approach to prolong
      pharmacokinetics and reduce burst release of a drug on subcutaneous delivery. The
      objective of this paper was to investigate the influence of phase structures of a
      lipid-based liquid crystal delivery system and its associated mechanical
      properties on the release profile of a peptide. It was hypothesized that release
      of drug molecules are closely related to the mechanical properties that are
      controlled by phase structures. Experimentally, the relationship between phase
      structures of lipid liquid crystal system-soy phosphatidyl choline (SPC) and
      glycerol dioleate (GDO) in water were characterized by polarized light microscopy
      and small angle X-ray diffraction. Their rheological properties were evaluated
      with a rheometer and the in vitro release of the peptide as a measure drug
      release from the LC-depot injection. Three phases: disordered phase, lamellar
      phase, mixtures of cubic, lamellar, and hexagonal phases were detected by varying
      formulation compositions. A significant difference in rheological behavior was
      observed. The disordered phase displayed some attributes of typical Newtonian
      fluid with lowest viscosity while the lamellar phase showed a shear thinning
      behavior. Regarding the mechanical strength, the lamellar phase presents the
      highest storage modulus due to its layer structure followed by mixed phases.
      Comparing release profiles, the lamellar phase produced a fast release followed
      by the mixture of phases. In conclusion, this study demonstrates the ability to
      characterize LC phase structures with microscopy, small angle X-ray diffraction,
      and rheological measurements and their link to modulating a peptide release
      profile.

PMID- 28741140
TI  - Melt Extrusion for a High Melting Point Compound with Improved Solubility and
      Sustained Release.
AB  - The objective of the current study was to develop an amorphous solid dispersion
      for a high melting point compound, griseofulvin (GRF), with an enhanced
      solubility and a controlled release pattern utilizing hot melt extrusion (HME)
      technology. Hypromellose acetate succinate (HPMCAS, Shin-Etsu AQOAT(r), medium
      particle size) was explored as the polymeric carrier, while hypromellose (HPMC,
      Metolose(r) SR) was chosen as the release rate control agent. GRF presented an
      HPMCAS grade-dependent solubility: AS-HMP > AS-MMP > AS-LMP. At 10 wt.% loading,
      the release of GRF was prolonged to 6 h with the incorporation of 10% HPMC 90SH
      100SR, while its solubility was enhanced up to sevenfold. Fourier transform
      infrared spectroscopy (FT-IR) identified the H-bonding between drug and polymers.
      Element analysis utilizing X-ray photoelectron spectroscopy (XPS) discovered that
      less GRF aggregated on the surface of binary powders compared with ternary
      powders containing HPMC, indicating the relatively poor wettability of the latter
      one. The morphology of extrudates was observed by scanning electron microscopy
      (SEM) and atomic force microscopy (AFM), illustrating a much smoother and uniform
      surface of binary extrudates. Immediate release tablets including 10% super
      disintegrant L-HPC were able to achieve identical dissolution profile as the
      powders of extrudates.

PMID- 28741141
TI  - Detonation nanodiamonds are promising nontoxic delivery system for urothelial
      cells.
AB  - Detonation nanodiamonds (DNDs) are carbon-based nanomaterials that are among the
      most promising nanoparticles available for biomedical applications so far. This
      is due to their biocompatibility, which could be contributed to their inert core
      and conformable surface nature. However, DNDs cytotoxicity for urothelial cells
      and the routes of their internalization remains an open question in the aspect of
      nanodiamond surface. We therefore analyzed four types of DNDs for cytotoxicity
      and internalization with normal urothelial cells and two types of cancer
      urothelial cell lines in vitro. Viability of any of the cell types we used was
      not compromised with any of four DNDs we evaluated after 24-, 48- and 72-h
      incubation in three different concentrations of DNDs. Transmission electron
      microscopy revealed that all four types of DNDs were endocytosed into all three
      types of urothelial cells tested here. We observed DNDs in endosomes, as well as
      in multivesicular bodies and multilamellar bodies. These results propose using of
      DNDs as a delivery system for urological applications in human nanomedicine.

PMID- 28741142
TI  - Proteomic Expression Changes in Large Cerebral Arteries After Experimental
      Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway.
AB  - Subarachnoid hemorrhage (SAH) is a serious clinical condition where leakage of
      blood into the subarachnoid space causes an acute rise in intracranial pressure
      and reduces cerebral blood flow, which may lead to delayed cerebral ischemia and
      poor outcome. In experimental SAH, we have previously shown that the outcome can
      be significantly improved by early inhibition of the MAPK/ERK
      kinase/extracellular signal-regulated kinase (MEK/ERK1/2) pathway. The aim of
      this study was to apply mass spectrometry to investigate the overall late effects
      of experimental SAH on cerebrovascular protein expression. SAH was induced in
      rats that were treated with the MEK1/2 inhibitor U0126 or vehicle. Neurological
      outcome was assessed using a battery of behavioral tests. Specific protein
      expression of large cerebral arteries was analyzed quantitatively with high
      throughput tandem mass spectrometry. SAH resulted in a marked reduction of
      neurological scores, which was counteracted by U0126 treatment. Mass spectrometry
      analysis demonstrated regulation of 184 proteins after SAH, regulations that were
      in part prevented by U0126 treatment. Network analysis identified several protein
      networks including a strong structural network centered around 14-3-3.
      Additionally, protein networks with functions in mRNA metabolism and protein
      folding were identified. Treatment with U0126 inhibited cerebral vessel wall
      pERK1/2 expression and significantly improved outcome of the rats. In conclusion,
      we show that SAH induces a broad array of specific changes in the overall protein
      networks in cerebral artery smooth muscle cells and suggest that this is
      essential for understanding the vascular pathophysiology after SAH.

PMID- 28741143
TI  - Salidroside Ameliorates Diabetic Neuropathic Pain in Rats by Inhibiting
      Neuroinflammation.
AB  - More than half of diabetic patients suffer from intractable neuropathic pain. As
      inflammation plays an important role in diabetic neuropathic pain, anti
      inflammatory drugs might have therapeutic potentials for neuropathic pain.
      Salidroside (SAL), a phenylpropanoid glucoside, modulates a variety of cell
      functions, including inflammation. Here, we explored anti-nociceptive and anti
      inflammatory effects of SAL on Zucker diabetic fatty rats with type 2 diabetes
      (DM rats). DM rats were tested for mechanical and thermal hyperalgesia using von
      Frey filament and plantar hot box test, respectively. The anti-nociceptive effect
      of chronic SAL (25-100 mg/kg, per oral) treatment was tested. The expression of
      inflammatory cytokines (TNF-alpha and IL-1beta) and P2X7 receptors in spinal cord
      and sciatic nerve were measured with ELISA. SAL alleviated mechanical and thermal
      hyperalgesia and reduced TNF-alpha and IL-1beta in sciatic nerve and spinal cord
      in DM rats. Furthermore, SAL reduced P2X7 receptor upregulation in spinal cord of
      DM rats and directly inhibited P2X7 receptors expressed in HEK293 cells. This
      study provides evidence that SAL attenuated nociception in diabetic neuropathic
      pain rat models probably through inhibiting neuroinflammation and P2X7 receptors.

PMID- 28741144
TI  - Tobacco Use and Smoke Exposure in Children: New Trends, Harm, and Strategies to
      Improve Health Outcomes.
AB  - PURPOSE OF REVIEW: Every day in the USA, approximately 4000 adolescents begin
      smoking and the adolescent brain is particularly susceptible to nicotine
      addiction. We present current pediatric trends on tobacco use and exposures,
      various new products used by adolescents, the adverse biological and behavioral
      effects of tobacco use and exposures, and tobacco control strategies to eliminate
      tobacco-related illnesses and deaths in the pediatric population. RECENT
      FINDINGS: Twelve-20% of women continue to smoke during pregnancy. New research
      reveals cognitive differences and behavior-control disorders are seen in
      elementary school children from prenatal and postnatal exposures. Traditional
      cigarette smoking has decreased in adolescents; novel and appealing tobacco
      products have captured their attention, particularly electronic cigarettes, and
      rates double and often triple from middle to high school. Children with asthma
      and those living in multi-housing units have higher rates of secondhand smoke
      exposure than non-asthmatics and children living in single-home dwellings. There
      is no "safe or risk-free" level of tobacco use or exposure. Tobacco use and
      exposure in childhood and adolescence must be decreased using evidenced-based
      strategies to improve child health.

PMID- 28741145
TI  - Thigh muscle and subcutaneous tissue thickness measured using ultrasound imaging
      in older females living in extended care: a preliminary study.
AB  - BACKGROUND: Thigh tissue thickness has not been examined in older females living
      in extended care in UK as an indicator of musculoskeletal health. This study
      examined the feasibility of using ultrasound imaging to measure the thickness of
      superficial (fat) and deep layers (muscle) of the thigh in older females living
      in extended care. METHODS: In ten older females in extended care (aged 80-98
      years, mean 88 +/- 6.8; body mass: 56.5 +/- 12.6 kg) images of the anterior thigh
      (dominant) were taken in supine using B-mode ultrasound imaging. Superficial and
      deep layers were measured and percentage thickness was calculated. Independent t
      tests compared data from those in extended care to ten sedentary females living
      independently (aged 80-90 years, mean 84 +/- 3.6; body mass: 61.6 +/- 10.0 kg).
      RESULTS: Thickness of the superficial layers was not significantly different
      between the two groups (CI -0.017 to 0.815, p = 0.059). However, those living in
      extended care had greater (p < 0.001) muscle thickness (mean 2.75 +/- 0.48 cm)
      than those living independently (mean 1.83 +/- 0.3 cm), which was similarly
      significant when normalised for body mass (extended care 0.51 +/- 0.16;
      independent living 0.30 +/- 0.06). CONCLUSIONS: These novel findings showed it is
      feasible to use ultrasound to measure muscles in older females in extended care
      and that muscle thickness was larger than in those living independently. The
      reason for the difference seen between groups would need to be confirmed by a
      larger study that also examined factors related to risk of sarcopenia and
      frailty, such as nutrition and physical activity levels.

PMID- 28741146
TI  - Letter to the Editor concerning "Normative values for the spine shape parameters
      using 3D standing analysis from a database of 268 asymptomatic Caucasian and
      Japanese subjects" by JC Le Huec et al. Eur Spine J (2016) 25:3630-3637.

PMID- 28741147
TI  - Constipation in degenerative cervico-thoracic spine myelopathy: a simple co
      existence or a complex inter-relationship?
AB  - PURPOSE: Identify factors affecting constipation and post surgical improvement in
      patients of myelopathy. METHODS: Sixty-four patients with myelopathy due to
      extradural spine pathologies (47 cervical; 17 thoracic spine, male:female-5.4:1
      with mean age 46.16) underwent evaluation including Bristol stool scale (BSS),
      PFT and uroflowmetry. All cases were evaluated by gastroenterologist to rule out
      any intrinsic bowel disease. Chi-square test, Kruskal-Wallis/Mann-Whitney U test
      and Wilcoxon signed rank test were employed to ascertain statistical
      significance. RESULTS: The presence of constipation was associated with male sex
      (p = 0.01), degree of constipation with duration bladder symptoms (p = 0.008) and
      numbness (p = 0.04). The improvement in BSS after surgery (p = 0.006) was
      associated with local pain (p = 0.02), duration of weakness (p = 0.04) and
      overall symptoms (p = 0.01), also with pulmonary function tests (p = 0.002) and
      pre-operative Nurick's grade (p = 0.01). CONCLUSION: Constipation is a
      myelopathic symptom as it is relieved by cord decompression and the gender, PFT
      and the duration of symptoms play an important role in defining constipation and
      expected improvement in these patients.

PMID- 28741148
TI  - Simultaneous navigated cervico-thoracic and thoraco-lumbar fixation.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To investigate the feasibility of using two
      independent image guidance systems to simultaneously fix multiple segment spine
      fractures. Image guidance is increasingly used to aid spinal fixation. We
      describe the first use of multiple navigation systems during a single procedure
      allowing for multi-segment spinal fixations to be performed simultaneously and
      capitalizing the advantages of navigation. METHOD: Two Medtronic Stealth Station
      S7TM systems with O-arm image capture were used to guide fixation of C6 and T12,
      unstable, AO A4, three-column fractures, in a patient with ankylosing
      spondylitis. RESULTS: Two surgical teams were able to perform cervico-thoracic
      and thoraco-lumbar fixations simultaneously. Operative time was 2.5 h. Post
      operative imaging showed accurate instrumentation placement. The patient
      recovered without any neurological sequelae. CONCLUSIONS: Optical independence of
      the Medtronic Stealth StationTM system allowed for simultaneous navigation guided
      fixation of multiple segment fractures without compromising accuracy. This may
      result in shortened operative time and morbidity associated with prolonged prone
      positioning of polytrauma patients, as well as reducing radiation exposure for
      theatre staff.

PMID- 28741149
TI  - The role of peripheral interleukin-6 in the development of acute seizures
      following virus encephalitis.
AB  - Seizure disorders are often associated with infectious etiologies. Infection, via
      the intracerebral (i.c.) route, of C57BL/6J mice with the Daniels (DA) strain of
      Theiler's murine encephalomyelitis virus (TMEV) results in approximately 50% of
      the mice developing acute behavioral seizures. TMEV-DA is the wild-type strain of
      the virus that replicates within the parenchyma of the brain. A variant of TMEV
      DA, TMEV-H101, does not replicate within the parenchyma of the brain. However,
      infection with TMEV-H101 via the i.c. route still results in approximately 40% of
      the mice developing acute behavioral seizures. Infiltrating macrophages producing
      interleukin-6 (IL-6) have been implicated in the induction of acute seizures
      following TMEV-DA infection. We examined macrophage infiltration and microglial
      activation within the brain and cytokine levels in the periphery in mice infected
      with TMEV-DA or TMEV-H101 and assessed the effects of the addition of recombinant
      IL-6 to the periphery in wild-type and IL-6 knockout mice infected with TMEV-DA.
      We found that pathologic levels of IL-6 in the periphery may play a role in the
      development of seizures when viral replication within the brain is limited.
      Examination of the role played by the peripheral immune system in the development
      of seizures/epilepsy in the TMEV-induced seizure model, the first viral infection
      driven model for epilepsy, could lead to the elucidation of novel therapeutics.

PMID- 28741150
TI  - Eslicarbazepine Acetate: A New Improvement on a Classic Drug Family for the
      Treatment of Partial-Onset Seizures.
AB  - Eslicarbazepine acetate is a new anti-epileptic drug belonging to the
      dibenzazepine carboxamide family that is currently approved as adjunctive therapy
      and monotherapy for partial-onset (focal) seizures. The drug enhances slow
      inactivation of voltage-gated sodium channels and subsequently reduces the
      activity of rapidly firing neurons. Eslicarbazepine acetate has few, but some,
      drug-drug interactions. It is a weak enzyme inducer and it inhibits cytochrome
      P450 2C19, but it affects a smaller assortment of enzymes than carbamazepine.
      Clinical studies using eslicarbazepine acetate as adjunctive treatment or
      monotherapy have demonstrated its efficacy in patients with refractory or newly
      diagnosed focal seizures. The drug is generally well tolerated, and the most
      common side effects include dizziness, headache, and diplopia. One of the
      greatest strengths of eslicarbazepine acetate is its ability to be administered
      only once per day. Eslicarbazepine acetate has many advantages over older anti
      epileptic drugs, and it should be strongly considered when treating patients with
      partial-onset epilepsy.

PMID- 28741151
TI  - Probiotic Characteristics of Lactobacillus curvatus DN317, a Strain Isolated from
      Chicken Ceca.
AB  - The probiotic characteristics of Lactobacillus curvatus DN317, a strain isolated
      from chicken ceca, were evaluated. This strain was selected for study from the
      isolated Lactobacillus strains because it has specific anti-microbial activity
      against Campylobacter jejuni ATCC 33560, Camp. jejuni NCTC 11168, Listeria
      monocytogenes ATCC 7644, and Bacillus subtilis ATCC 8633. Lact. curvatus DN317
      showed an auto-aggregation percentage of 72% and presented the highest co
      aggregation with Lact. monocytogenes ATCC 7644 (68%) compared to B. subtilis ATCC
      8633 (45%), Camp. jejuni ATCC 33560 (36%), and Camp. jejuni NCTC 11168 (35%). The
      data revealed that Lact. curvatus DN317 could survive at 0.25% bile, maintain
      viability at pH 2.5 for 30 min, produce biosurfactants, and adhere to Caco-2
      cells. Quantification of IL-6, IL-8, IL-10, and beta-defensin 2 levels shows that
      Lact. curvatus DN317 induces an increase in IL-8 and beta-defensin 2 secretion,
      while the levels of IL-6 and IL-10 do not change. Lact. curvatus DN317 showed
      high levels of esterase and cysteine arylamidase activities (5); moderate levels
      of esterase lipase, beta-galactosidase, and alpha-galactosidase activities (4,
      3); and weak levels of leucine arylamidase, valine arylamidase, and acid
      phosphatase activity (1). Various activities were obtained of alpha-chymotrypsin,
      beta-glucuronidase, beta-glucosidase, and N-acetyl-beta-glucosaminidase, which
      have been associated with intestinal diseases. Lact. curvatus DN317 lowered the
      cholesterol level in MRS with and without bile. Antibiotic susceptibility tests
      indicated that DN317 was sensitive to ampicillin, gentamicin, kanamycin,
      streptomycin, tetracycline, clindamycin, erythromycin, and vancomycin but was
      resistant to chloramphenicol and ciprofloxacin. These results suggest that Lact.
      curvatus DN317 could potentially function as a probiotic.

PMID- 28741152
TI  - Evaluation of Probiotic Diversity from Soybean (Glycine max) Seeds and Sprouts
      Using Illumina-Based Sequencing Method.
AB  - There is increasing interest in the use of plant probiotics as environmental
      friendly and healthy biofertilizers. The study aimed at selecting for novel
      probiotic candidates of soybean (Glycine max). The bacteriome and mycobiome of
      soybean sprouts and seeds were analyzed by Illumina-based sequencing. Seeds
      contained more diverse bacteria than those in sprouts. The seeds contained
      similar fungal diversity with sprouts. Total 15 bacterial OTUs and 4 fungal OTUs
      were detected in seeds and sprouts simultaneously, suggesting that the sprouts
      contained bacterial and fungal taxa transmitted from seeds. The Halothiobacillus
      was the most dominant bacterial genus observed and coexisted in seeds and
      sprouts. The OTUs belonged to Ascomycota were the most dominant fungal taxa
      observed in seeds and sprouts. Halothiobacillus was firstly identified as
      endophytic probiotics of soybean. The results suggested that sprouts might
      contain diverse plant probiotics of mature plants and Illumina-based sequencing
      can be used to screen for probiotic candidates.

PMID- 28741153
TI  - Recovery of ACL function after dynamic intraligamentary stabilization is
      resultant to restoration of ACL integrity and scar tissue formation.
AB  - PURPOSE: Dynamic intraligamentary stabilization (DIS) is recognized as a ligament
      preserving technique for the treatment of acute anterior cruciate ligament (ACL)
      injuries. The aim of this study was to assess the integrity and morphology of the
      recovered ACL after DIS repair. METHODS: The cohort comprised 47 patients with an
      acute proximal ACL rupture undergoing DIS repair. All patients underwent
      diagnostic arthroscopy after a minimum postoperative interval of 6 months for
      semi-quantitative evaluation of ACL integrity, function and scar tissue
      formation. Tegner, Lysholm and International Knee Documentation Committee (IKDC)
      scores as well as objective anteroposterior (ap) translation were assessed at 6
      weeks, 3-, 6-  and 12 months postoperatively. RESULTS: Full restoration of the
      ACL volume was affirmed in 30 (63.8%) patients and two-third restoration in 13
      (27.7%). Hypertrophic scar formation was observed in 23 (48.9%) patients. Forty
      four patients (93.6%) demonstrated sufficient ACL tensioning intraoperatively
      upon anterior stress. At final follow-up, the median Tegner activity level was
      5.5 (3-10), Lysholm and IKDC scores were 100 (64-100) and 94 (55-100) points,
      respectively. The mean ap-translation differed from the normal knee by 2.1 +/-
      2.2 mm. Deficient ACL recovery was noted in four patients (8.5%), none of which
      required secondary reconstructive surgery. CONCLUSION: The results demonstrate
      that clinical recovery of ACL function after DIS repair is resultant to both
      restoration of ACL volume and scar tissue formation. Factors influencing the
      degree of scar tissue formation need further investigation to enable future
      attempts of guiding a balanced biological healing response. LEVEL OF EVIDENCE:
      IV.

PMID- 28741154
TI  - Erratum to: Popliteus impingement after TKA may occur with well-sized prostheses.

PMID- 28741155
TI  - Length change patterns and shape of a grafted tendon after anatomical medial
      patellofemoral ligament reconstruction differs from that in a healthy knee.
AB  - PURPOSE: Recurrent patellar dislocation is currently treated with anatomical
      reconstruction of the medial patellofemoral ligament (MPFL), and favourable
      postoperative outcomes have been reported. However, it is uncertain if healthy
      MPFL function is restored by anatomical reconstruction. The hypothesis in this
      study was that stabilization of the patella following MPFL reconstruction would
      be improved compared with that before surgery, but that function of the grafted
      tendon would differ from that of a healthy MPFL. The objective was to analyse the
      length change patterns of the MPFL before surgery and the grafted tendon after
      surgery in patients with recurrent patellar dislocation treated with anatomical
      MPFL reconstruction. METHODS: The subjects were 12 patients (13 knees) in whom
      recurrent patellar dislocation was treated with anatomical MPFL reconstruction.
      The length change patterns of the MPFL and reconstructed ligament were analysed
      at extension and flexion of the knee joint using open MRI. RESULTS: The
      postoperative grafted tendon length was significantly shorter than that of the
      preoperative MPFL at knee extension, and significantly longer at 90 degrees  and
      120 degrees  of knee flexion. The postoperative length of the grafted tendon only
      changed slightly from 0 degrees  to 30 degrees  of knee flexion, and then
      significantly decreased at flexion of 30 degrees  or more. The morphology of the
      grafted tendon was linear until 60 degrees  knee flexion, but became convex
      toward the extraarticular side at flexion of 90 degrees  or more. CONCLUSION: The
      grafted tendon length at knee extension was shorter than that of the preoperative
      MPFL, but there was no significant difference at 30 degrees  flexion. These
      findings suggest that the effect of damping of the patella with a grafted tendon
      after MPFL reconstruction may differ from that in a healthy knee. In addition,
      the morphology at 60 degrees  knee flexion was improved to linear after surgery,
      suggesting that ligament morphology at this flexion was normalized by MPFL
      reconstruction. LEVEL OF EVIDENCE: III.

PMID- 28741156
TI  - Response to the Letter from Landman et al.

PMID- 28741157
TI  - Eicosapentaenoic acid protects cardiomyoblasts from lipotoxicity in an autophagy
      dependent manner.
AB  - BACKGROUND AND AIMS: The cardiovascular health benefits of eicosapentaenoic acid
      (EPA) have been demonstrated previously; however, the exact mechanism underlying
      them remains unclear. Our previous study found that lipotoxicity induced
      cardiomyocyte apoptosis via the inhibition of autophagy. Accordingly, in this
      study, we investigated whether EPA attenuated lipotoxicity-induced cardiomyocyte
      apoptosis through autophagy regulation. The role of EPA in mitochondrial dynamics
      was analyzed as well. METHODS: To explore how EPA protected against lipotoxicity
      induced myocardial injury, cardiomyoblast (H9C2) cells were left untreated or
      were treated with 400 MUM palmitic acid (PAM) and/or 80 MUM EPA for 24 h.
      RESULTS: Excessive PAM treatment induced apoptosis. EPA reduced this PAM-induced
      apoptosis; however, EPA was unable to ameliorate the effects of PAM when
      autophagy was blocked by 3-methyladenine and bafilomycin A1. PAM blocked the
      autophagic flux, thus causing the accumulation of autophagosomes and acid
      vacuoles, whereas EPA restored the autophagic flux. PAM caused a decrease in
      polyunsaturated fatty acid (PUFA) content and an increase in saturated fatty acid
      content in the mitochondrial membrane, while EPA was incorporated in the
      mitochondrial membrane and caused a significant increase in the PUFA content. PAM
      also decreased the mitochondrial membrane potential, whereas EPA enhanced it.
      Finally, PAM elevated the expressions of autophagy-related proteins (LC3I, LC3II,
      p62) and mitochondrial fission protein (Drp1), whereas EPA inhibited their
      elevation under PAM treatment. CONCLUSIONS: EPA reduces lipotoxicity-induced
      cardiomyoblast apoptosis through its effects on autophagy.

PMID- 28741158
TI  - Intraocular lenses in age-related macular degeneration.
AB  - PURPOSE: The aim of this work is to review the lenses, assessing their advantages
      and disadvantages. We describe a total of seven types of intraocular lenses
      (IOLs) recommended for age-related macular degeneration (AMD). METHODS: We used
      the PubMed web platform to search for implantable devices in various stages of
      AMD. We searched for both prospective and retrospective studies and also case
      reports. RESULTS: Clinical results in AMD patients have been described for a
      total of seven types of IOLs recommended for AMD: an implantable miniature
      telescope (IMT), IOL-VIP System, Lipshitz macular implant (LMI), sulcus-implanted
      Lipshitz macular implant, LMI-SI, Fresnel Prism Intraocular Lens, iolAMD and
      Scharioth Macula Lens. CONCLUSIONS: We conclude that to objectively ascertain the
      effectiveness and safety of these lenses, further independent clinical studies
      with longer follow-up data are necessary prior to the general use of these
      optical devices.

PMID- 28741159
TI  - Sebaceous gland carcinoma of the ocular adnexa - variability in clinical and
      histological appearance with analysis of immunohistochemical staining patterns.
AB  - PURPOSE: The purpose of the study was to evaluate the characteristics of
      sebaceous gland carcinoma (SGC) of the ocular adnexae, which is due to a high
      variability in clinical, histological and immunohistochemical characteristics
      often challenging to diagnose. METHODS: Records of six patients with SGC were
      reviewed, who underwent surgical excision and who were histologically diagnosed
      with SGC. For comparison, there were specimens from four patients with basal cell
      carcinoma (BCC) and four patients with squamous cell carcinoma (SCC).
      Histological and immunohistochemical analysis included stains for HE,
      cytokeratins (CKpan, Cam5.2), epithelial membrane antigen (EMA), androgen
      receptor (AR441), perforin and adipophilin. RESULTS: SGC's were located in the
      upper (n = 2) or lower (n = 4) eyelid and were associated with various presenting
      clinical signs including chalazion-like lesions with pyogenic granuloma (n = 1),
      papillomatous conjunctival tumors (n = 3), a hyperkeratotic exophytic neoplasm (n
      = 1) and an ulcerating crusted lesion resembling chronic blepharitis (n = 1). The
      treatment was tumor resection, followed (if necessary) by adjuvant therapy with
      topical Mitomycin C (n = 2). Histologic characteristics included basophilic
      pleomorphic cells with vacuolated cytoplasm, prominent nucleoli, mitotic figures
      and in some cases pagetoid spread (n = 2). CKpan, EMA and Cam5.2 showed strong
      positive immunoreactivity in all specimens (SGC, BCC, SCC). Perforin
      immunostaining showed a varying, but overall weak, non-specific cytoplasmatic
      staining reaction in all lesions. AR441 positivity was noted with variable
      intensity in almost all lesions and in particular in pagetoid spread in contrast
      to non-tumor cells. Adipophilin showed an annular staining of lipid granules in
      immature sebaceous cells in SGC in contrast to a more granular staining pattern
      in BCC and SCC. CONCLUSION: SGCs display a variety of clinical signs and may
      mimic many other lesions. Tumor resection, followed by histological and
      immunohistochemical analysis, leads to the diagnosis and initiation of the proper
      treatment regimen. Herein, immunohistochemistry showed an unequivocal profile in
      SGC and did not allow for an exact differentiation from BCC and SCC by
      immunohistochemical means only. An extended evaluation of HE stains remains
      essential. However, immunohistochemistry can make relevant contributions to the
      diagnosis of SGC, especially in cases of inconclusive histology, by positive
      staining for adipophilin in immature sebaceous cells or by AR441 labeling in
      cases of pagetoid spread.

PMID- 28741160
TI  - Erratum to: Treadmill Exercise Attenuates alpha-Synuclein Levels by Promoting
      Mitochondrial Function and Autophagy Possibly via SIRT1 in the Chronic MPTP/P
      Induced Mouse Model of Parkinson's Disease.

PMID- 28741161
TI  - [Therapy-associated corneal pathologies].

PMID- 28741162
TI  - [Scanning electron microscopic investigations of cutting edge quality in lamellar
      keratotomy using the Wavelight femtosecond laser (FS-200) : What influence do
      spot distance and an additional tunnel have?]
AB  - BACKGROUND: Femtosecond lasers (fs-lasers) are established cutting instruments
      for the creation of LASIK flaps. Previous studies often showed even rougher
      surfaces after application of fs-laser systems compared to lamellar keratotomy
      with mechanical microkeratomes. When cutting the cornea with fs-lasers, an
      intrastromal gas development occurs, which has a potentially negative influence
      on the cutting quality if the gas cannot be dissipated; therefore, manufacturers
      have chosen the way of gas assimilation in so-called pockets. The investigated
      system creates a tunnel which opens under the conjunctiva. The aim of this study
      was to investigate the effects of a tunnel as well as the influence of different
      spot distances on the quality of cut surfaces and edges. MATERIAL AND METHODS: In
      this experimental study on freshly enucleated porcine eyes (n = 15), the
      following cuts were carried out with the FS-200 (Wavelight, Erlangen, Germany):
      1. standard setting (spot and line separation 8 um), 2. with tunnel for gas
      drainage, 3. without gas-conducting tunnel, 4. with increased spot spacing (spot
      and line separation 9 MUm instead of 8 MUm) and 5. with reduced spot spacing
      (spot and line separation 7 MUm instead of 8 MUm). Subsequently, scanning
      electron microscopy (FEI Quanta 650, Hillsboro, OR) of the cut edges and surfaces
      as well as the gas drain tunnel were performed. The evaluation was based on an
      established score. RESULTS: The current fs-laser system (200 Hz) is able to
      create smooth cutting surfaces and sharp edges. The changed density of laser
      pulses compared to the standard settings with a reduced or increased distance
      between the pulses, did not achieve any further improvement in the surface
      quality. The gas-conducting tunnel could be detected by scanning electron
      microscope. In the case of cutting without a tunnel, roughened surfaces and
      irregularities on the cutting edges were found. CONCLUSION: When the FS-200 fs
      laser is used, LASIK cuts with very smooth cut surfaces and sharp cutting edges
      are achieved. This is only valid as long as an additional tunnel with the fs
      laser is placed under the conjunctiva. It can be assumed that the resulting gas
      is effectively drained through this tunnel. The installation of the tunnel
      represents a new possibility to replace previous techniques of gas assimilation
      in deeper lying cutting areas.

PMID- 28741163
TI  - [Visual improvement by aberration-free excimer laser retreatment : Therapy after
      combined photorefractive keratectomy and keratome laser in situ keratomileusis
      treatment].
AB  - A 23-year-old male patient presented with reduced visual acuity of the right eye,
      along with halos and starbursts in both eyes after a one-stage tissue-saving
      treatment, a combination of myopic photorefractive keratectomy (PRK) and laser in
      situ keratomileusis (LASIK). After an extensive preliminary examination and
      analysis of the examination results, aberration-free LASIK retreatment for
      reducing astigmatism and enlargement of the optical zone with an excimer laser
      was performed on the right eye. The visual performance and the subjectively
      perceived optical quality improved postoperatively.

PMID- 28741164
TI  - [Developments and inventions from Germany : Influence on international
      ophthalmology].
AB  - There are various developments and inventions from Germany that have influenced
      not only the domestic but also the international field of ophthalmology.
      Beginning with the invention of the ophthalmoscope by Hermann von Helmholtz in
      1850, to the establishment of the "Archives of Ophthalmology" medical journal, a
      publication founded by Albrecht von Graefe in 1854, through to the development of
      the retinal chip by Eberhart Zrenner and colleagues with the first clinical data
      collected in 2007. The abovenamed and further developments and the German
      ophthalmologists behind these inventions are discussed in more detail.

PMID- 28741165
TI  - History and conceptual developments in vascular biology and angiogenesis
      research: a personal view.
AB  - Vascular biology is an important scientific domain that has gradually penetrated
      many medical and scientific fields. Scientists are most often focused on present
      problems in their daily scientific work and lack awareness regarding the
      evolution of their domain throughout history and of how philosophical issues are
      related to their research field. In this article, I provide a personal view with
      an attempt to conceptualize vascular development research that articulates
      lessons taken from history, philosophy, biology and medicine. I discuss selected
      aspects related to the history and the philosophy of sciences that can be
      extracted from the study of vascular development and how conceptual progress in
      this research field has been made. I will analyze paradigm shifts, cross
      fertilization of different fields, technological advances and its impact on
      angiogenesis and discuss issues related to evolutionary biology, proximity of
      different molecular systems and scientific methodologies. Finally, I discuss
      briefly my views where the field is heading in the future.

PMID- 28741166
TI  - A new key player in VEGF-dependent angiogenesis in human hepatocellular
      carcinoma: dimethylarginine dimethylaminohydrolase 1.
AB  - BACKGROUND: Anti-angiogenic therapies, targeting VEGF, are a promising treatment
      for hepatocellular carcinoma (HCC). To enhance this potential therapy,
      identification of novel targets in this pathway is of major interest. Nitric
      oxide (NO) plays a crucial role in VEGF-dependent angiogenesis. NO production
      depends on arginine as substrate and asymmetric dimethylarginine (ADMA) as
      inhibitor. Dimethylarginine dimethylaminohydrolase 1 (DDAH-1) catabolizes ADMA
      and therefore regulates NO and VEGF expression. This study unravels additional
      mechanisms to improve VEGF targeting therapies. METHODS: The expression of DDAH-1
      was examined in HCC specimen and non-tumorous background liver of 20 patients
      undergoing liver resection. Subsequently, arginine/ADMA balance, NO production,
      and VEGF expression were analyzed. The influence of hypoxia on DDAH-1 and
      angiogenesis promoting factors was evaluated in HepG2 cells and primary human
      hepatocytes. RESULTS: DDAH-1 expression was significantly induced in primary HCC
      tumors compared to non-tumorous background liver. This was associated with an
      increased arginine/ADMA ratio, higher NO formation, and higher VEGF expression in
      human HCC compared to non-tumorous liver. Hypoxia induced DDAH-1, iNOS, and VEGF
      expression in a time-dependent manner in HepG2 cells. CONCLUSIONS: Our results
      indicate that DDAH-1 expression is increased in human HCC, which is associated
      with an increase in the arginine/ADMA ratio and enhanced NO formation. Hypoxia
      may be an initiating factor for the increase in DDAH-1 expression. DDAH-1
      expression is associated with promotion of angiogenesis stimulating factor VEGF.
      Together, our findings for the first time identified DDAH-1 as a key player in
      the regulation of angiogenesis in human HCC, and by understanding this mechanism,
      future therapeutic strategies targeting VEGF can be improved.

PMID- 28741168
TI  - Success and complications of percutaneous transhepatic biliary drainage are
      influenced by liver entry segment and level of catheter placement.
AB  - PURPOSE: To examine outcomes and complications of percutaneous transhepatic
      biliary drainage (PTBD) performed via the right or left lobe and different entry
      levels (lobar, segmental, subsegmental, sub-subsegmental). METHODS: The records
      of patients who underwent PTBD for obstructive jaundice from 2008 to 2015 were
      retrospectively reviewed. Logistic regression analysis was performed to determine
      factors associated with outcomes and complications based on entry side and entry
      level. PTBD success was defined as a total bilirubin decrease after catheter
      placement. RESULTS: The data of 446 patients (mean age 68.4 years) were included.
      Multivariate logistic regression revealed a decrease of bilirubin level was
      associated with left lobe (vs. right) entry [adjusted odds ratio (aOR) = 2.657,
      95% confidence interval (CI) 1.160, 6.087], external drainage (aOR = 2.908, 95%
      CI 1.226, 6.897), and liver volume undrained <50% (aOR = 2.623, 95% CI 1.045,
      6.581). PTBD success was increased with left lobe entry (aOR = 1.853, 95% CI
      1.167, 2.940) and associated with entry level (subsegmental vs. lobar, aOR =
      2.992, 95% CI 1.258, 7.114; sub-subsegmental vs. lobar, aOR = 3.711, 95% CI
      1.383, 9.956). Complications were significantly decreased with left lobe entry
      (aOR = 0.450, 95% CI 0.263, 0.769) and associated with entry level (segmental vs.
      lobar, aOR = 0.359, 95% CI 0.148, 0.873; subsegmental vs. lobar, aOR = 0.248, 95%
      CI 0.10, 0.615; sub-subsegmental vs. lobar, aOR = 0.129, 95% CI 0.041, 0.411).
      CONCLUSIONS: The success and complications of PTBD vary with entry side and
      level.

PMID- 28741167
TI  - Microvascular ultrastructural changes precede cognitive impairment in the murine
      APPswe/PS1dE9 model of Alzheimer's disease.
AB  - Cerebral and systemic organ microvascular pathologies coexist with human
      Alzheimer's disease (AD) neuropathology. In this study, we hypothesised that both
      cerebral and systemic microvascular pathologies exist in 4- to 5-month-old male
      APPswe/PS1dE9 (APP/PS1) transgenic mice prior to the onset of cognitive
      impairment. To assess this we examined recognition memory in both wild-type and
      APP/PS1 mice using the object recognition task (ORT; n = 11 per group) and
      counted thioflavin-S-positive plaques in brain (n = 6 per group). Vascular casts
      of brain, liver, spleen and kidneys were examined using scanning electron
      microscopy (n = 6 per group), and the urinary albumin-to-creatinine ratio (uACR;
      n = 5 per group) was measured as an index of glomerular permeability. Murine
      recognition memory was intact, as demonstrated by a significant preference for
      the novel object in the ORT paradigm. Brain sections of wild-type mice were
      devoid of thioflavin-S positivity, whereas age-matched APP/PS1 mice had an
      average of 0.88 +/- 0.22 thioflavin-S-positive plaques in the cortex, 0.42 +/-
      0.17 plaques in the dentate gyrus and 0.30 +/- 0.07 plaques in the cornus ammonis
      1 region. The profiles of casted cerebral capillaries of wild-type mice were
      smooth and regular in contrast to those of APP/PS1 mice which demonstrate
      characteristic (0.5-4.6 MUm) 'tags'. APP/PS1 mice also had a significantly
      reduced hepatic vessel number (p = 0.0002) and an increase in the number of
      splenic microvascular pillars (p = 0.0231), in the absence of changes in either
      splenic microvascular density (p = 0.3746) or glomerular ultrastructure. The
      highly significant reduction in uACR in APP/PS1 mice compared to wild-type (p =
      0.0079) is consistent with glomerular microvascular dysfunction. These findings
      highlight early microvascular pathologies in 4- to 5-month-old APP/PS1 transgenic
      mice and may indicate an amenable target for pharmacological intervention in AD.

PMID- 28741169
TI  - Bridging vessel sign.

PMID- 28741171
TI  - [Unresectable colorectal liver metastases : Prolonged survival with aggressive
      local therapy].

PMID- 28741170
TI  - Decreased global field synchronization of multichannel frontal EEG measurements
      in obsessive-compulsive disorders.
AB  - Global field synchronization (GFS) quantifies the synchronization level of brain
      oscillations. The GFS method has been introduced to measure functional
      synchronization of EEG data in the frequency domain. GFS also detects phase
      interactions between EEG signals acquired from all of the electrodes. If a
      considerable amount of local brain neurons has the same phase, these neurons
      appear to interact with each other. EEG data were received from 17 obsessive
      compulsive disorder (OCD) patients and 17 healthy controls (HC). OCD effects on
      local and large-scale brain circuits were studied. Analysis of the GFS results
      showed significantly decreased values in the delta and full frequency bands. This
      research suggests that OCD causes synchronization disconnection in both the
      frontal and large-scale regions. This may be related to motivational, emotional
      and cognitive dysfunctions.

PMID- 28741173
TI  - More on molar incisor hypomineralisation (MIH) and linear enamel hypoplasia (LEH)
      in archaeological human remains.

PMID- 28741172
TI  - Glass ionomer cement inhibits secondary caries in an in vitro biofilm model.
AB  - OBJECTIVES: The objective of this study was to investigate the effect of
      different glass ionomer cements on secondary caries inhibition in a fully
      automated in vitro biofilm model. MATERIALS AND METHODS: One hundred and twenty
      four extracted third molars received class V cavities and were filled with one
      conventional (Ketac Molar/KM), and two resin-modified glass ionomer cements
      (Photac Fil/PF, Ketac N100/KN, 3M Espe). A bonded resin composite (Single Bond
      Plus/Filtek Supreme XTE) served as control. After 14 days water storage at 37 
      degrees C, specimens were thermocycled (10,000 * 5/55  degrees C). Over a period
      of 10 days, specimens were subjected to cariogenic challenge for 3/4/6 h/day.
      Demineralization was caused by Streptococcus mutans (DSM 20523) alternatingly
      being rinsed over specimens using artificial saliva. After biological loading,
      teeth were cut longitudinally and demineralization depths were evaluated at the
      margins and at a distance of 0.5 mm from the margins using fluorescence
      microscopy. Marginal quality was investigated under a SEM at *200 magnification.
      RESULTS: Four-hour demineralization depths were for enamel margins (EM), enamel
      (E), dentin margin (DM), and dentin (D) (MUm +/- SD): KM: EM 12 +/- 8, E 33 +/-
      7, DM 56 +/- 11, D 79 +/- 6; PF: EM 19 +/- 13, E 34 +/- 13, DM 53 +/- 10, D 77 +/
      12; and KN: EM 26 +/- 5, E 38 +/- 6, DM 57 +/- 11, D 71 +/- 7. For all glass
      ionomer cements (GICs), demineralization depth at the margins was less compared
      to 0.5 mm distance, with demineralization depth having been correlated to
      duration of cariogenic challenge (ANOVA [mod. LSD, p < 0.05]). Compared to the
      bonded resin composite, all GICs exhibited caries inhibition at restoration
      margins in enamel and dentin. CONCLUSIONS: Fluoride-releasing GIC materials
      exhibit a secondary caries inhibiting effect in vitro. CLINICAL RELEVANCE: Glass
      ionomer cements have a higher secondary caries inhibiting effect than resin
      composites.

PMID- 28741174
TI  - Angiosarcoma around total hip arthroplasty: case series and review of the
      literature.
AB  - BACKGROUND: Angiosarcoma (AS) is a rare and malignant tumor which mainly arises
      in the skin and superficial soft tissue and less frequently in deep soft tissue
      and bones. Some cases of AS are described in association with vascular and
      orthopedic devices. Nonetheless, only a few cases of AS around THA are reported
      in the literature. MATERIALS AND METHODS: We describe five cases of AS arising
      around total hip arthroplasty who received surgery at our institution (Istituto
      Ortopedico Rizzoli, Bologna, Italy), and we report the cases described in
      literature. RESULTS: Foreign bodies such as polyethylene were demonstrated to
      have a carcinogenic role in animals, but reports of similar cases in humans are
      rare. Nevertheless, osteolysis induced by wear particles of polyethylene is a
      frequent event and could induce to desist form considering other more rare causes
      of osteolysis such as AS. This could be the reason why the diagnosis in several
      cases was significantly delayed. Common features of these cases could be helpful
      for doing a prompt diagnosis. The initial presentation is suggestive for septic
      or aseptic loosening with a massive osteolysis around the cup and/or the stem
      associated with peculiar aspects as bleeding and loss of weight. Frequently,
      needle biopsy is negative because foreign-body reaction might have "covered" the
      most relevant condition of epithelioid AS. CONCLUSIONS: In conclusion in a
      patient who presents with uncontrollable bleeding, loss of weight and massive
      osteolysis, AS must be actually considered as possible diagnosis.

PMID- 28741175
TI  - A randomized phase II trial of geriatric assessment and management for older
      cancer patients.
AB  - PURPOSE: Geriatric assessment and management (GAM) can identify current health
      issues and recommend interventions to optimize well-being of older adults, but no
      randomized trial has yet been completed in oncology. Therefore, a randomized
      phase 2 trial was conducted. METHODS: A two-group parallel single-blinded
      randomized phase II trial ( ClinicalTrials.gov Identifier: NCT02222259) enrolled
      patients aged >=70 years, diagnosed with stage 2-4 gastrointestinal,
      genitourinary, or breast cancer within 6 weeks of commencing chemotherapy at
      Princess Margaret Cancer Centre. The coprimary feasibility outcomes were the
      proportion of eligible patients enrolled and retained. The coprimary clinical
      outcomes were quality of life (QOL) (EORTC QLQ C30) and modification of cancer
      treatment. Descriptive and regression analyses using intent-to-treat analysis
      were conducted. RESULTS: Sixty-one persons (64%) agreed to participate (31
      allocated to intervention arm and 30 to control group). In the control group,
      more participants died and refused follow-up. The benefit of intervention over
      control on QOL at 3 months was greater for those who survived 6 months
      (difference 9.28; 95% CI -10.35 to 28.91) versus those who survived only 3 months
      (difference 6.55; 95% CI -9.63 to 22.73). CONCLUSIONS: This trial showed that it
      was feasible to recruit and retain older adults for a GAM study. Those who
      survived at least 6 months seemed to receive a greater QOL benefit than those who
      died or withdrew.

PMID- 28741176
TI  - Safety and feasibility of exercise interventions in patients with advanced
      cancer: a systematic review.
AB  - GOALS OF WORK: The beneficial effects of exercise in cancer patients are
      reasonably well-established, although research in this field has predominantly
      investigated cancer patients in the earlier stages of disease. However, the most
      recent evidence surrounding exercise interventions in advanced cancer populations
      has yet to be systematically evaluated. This review critically analyses the
      safety and feasibility of exercise interventions in patients with advanced
      cancer. METHODS: All randomised, non-randomised and prospective observational
      trials of exercise training interventions in patients with advanced cancer were
      included. 'Safety' was defined as the number and severity of reported adverse
      events during exercise training. 'Feasibility' was determined by participant
      adherence, attendance and/or study completion rates. RESULTS: A total of 25
      studies involving 1088 patients were included: 16 randomised controlled and nine
      prospective observational cohort trials. Seven studies included advanced lung
      cancer patients exclusively, while eight involved patients with various cancer
      diagnoses. Aerobic exercise was investigated in five studies, resistance training
      in two studies and combination training (aerobic and resistance) in 14 studies.
      Six minor adverse events were reported due to exercise. All of these were
      musculoskeletal in nature, resulting in two participants' withdrawal from the
      study. Exercise adherence ranged from 65 to 89% but was only described in nine
      studies. Attendance at each exercise session was described in a further nine
      studies, ranging from 59 to 100%. CONCLUSIONS: Implementation of exercise
      interventions appears to be safe and feasible in advanced cancer clinical
      practice, although targeted studies are required to determine the optimal
      exercise dose for specific cancer diagnoses.

PMID- 28741177
TI  - Birth/birth-death processes and their computable transition probabilities with
      biological applications.
AB  - Birth-death processes track the size of a univariate population, but many
      biological systems involve interaction between populations, necessitating models
      for two or more populations simultaneously. A lack of efficient methods for
      evaluating finite-time transition probabilities of bivariate processes, however,
      has restricted statistical inference in these models. Researchers rely on
      computationally expensive methods such as matrix exponentiation or Monte Carlo
      approximation, restricting likelihood-based inference to small systems, or
      indirect methods such as approximate Bayesian computation. In this paper, we
      introduce the birth/birth-death process, a tractable bivariate extension of the
      birth-death process, where rates are allowed to be nonlinear. We develop an
      efficient algorithm to calculate its transition probabilities using a continued
      fraction representation of their Laplace transforms. Next, we identify several
      exemplary models arising in molecular epidemiology, macro-parasite evolution, and
      infectious disease modeling that fall within this class, and demonstrate
      advantages of our proposed method over existing approaches to inference in these
      models. Notably, the ubiquitous stochastic susceptible-infectious-removed (SIR)
      model falls within this class, and we emphasize that computable transition
      probabilities newly enable direct inference of parameters in the SIR model. We
      also propose a very fast method for approximating the transition probabilities
      under the SIR model via a novel branching process simplification, and compare it
      to the continued fraction representation method with application to the 17th
      century plague in Eyam. Although the two methods produce similar maximum a
      posteriori estimates, the branching process approximation fails to capture the
      correlation structure in the joint posterior distribution.

PMID- 28741179
TI  - Activation of liver X receptor inhibits OCT2-mediated organic cation transport in
      renal proximal tubular cells.
AB  - Liver X receptor (LXR) is transcriptional factor that plays an important role in
      the regulation of energy metabolism such as cholesterol, lipid, and glucose
      metabolism as well as membrane transporters and channels. Using both in vitro and
      in vivo models, LXR regulation of the expression and function of renal organic
      cation transporter 2 (OCT2) was observed. Synthetic LXR agonist (GW3965) and
      endogenous LXR agonist (22R-hydroxycholesterol) significantly reduced the uptake
      of 3H-MPP+, a prototypic substrate of OCT2, in both OCT2- Chinese hamster ovary
      K1 and human renal proximal tubular cells (RPTEC/TERT1). GW3965 decreased
      transport activity of OCT2 via a reduction of the maximal transport rate of MPP+
      without affecting transporter affinity. The inhibitory effect of GW3965 was
      attenuated by co-treatment with LXR antagonist (fenofibrate) indicating the
      inhibition was LXR-dependent mechanism. In addition, co-treatment with a retinoic
      X receptor (RXR) ligand, 9-cis retinoic acid enhanced the inhibitory effect of
      GW3965, indicating negative regulation of OCT2 transport activity by the LXR/RXR
      complex. Treatment RPTEC/TERT1 cells with GW3965 significantly reduced OCT2
      protein expression without changing mRNA expression. In parallel, the effect of
      LXR activation on OCT2 function was investigated in intact mouse kidney. Treating
      mice with 50 mg/kg BW T0901317 for 14 days significantly decreased 3H-MPP+ uptake
      into renal cortical slices, correlating with decreased OCT2 protein expression in
      renal cortex without changes in mRNA expression levels. Taken together, LXR/RXR
      activation downregulates the protein expression and function of OCT2 in renal
      proximal tubule, suggesting LXR might affect the total profile of renal excretion
      of cationic compounds.

PMID- 28741178
TI  - Continuum and discrete approach in modeling biofilm development and structure: a
      review.
AB  - The scientific community has recognized that almost 99% of the microbial life on
      earth is represented by biofilms. Considering the impacts of their sessile
      lifestyle on both natural and human activities, extensive experimental activity
      has been carried out to understand how biofilms grow and interact with the
      environment. Many mathematical models have also been developed to simulate and
      elucidate the main processes characterizing the biofilm growth. Two main
      mathematical approaches for biomass representation can be distinguished:
      continuum and discrete. This review is aimed at exploring the main
      characteristics of each approach. Continuum models can simulate the biofilm
      processes in a quantitative and deterministic way. However, they require a
      multidimensional formulation to take into account the biofilm spatial
      heterogeneity, which makes the models quite complicated, requiring significant
      computational effort. Discrete models are more recent and can represent the
      typical multidimensional structural heterogeneity of biofilm reflecting the
      experimental expectations, but they generate computational results including
      elements of randomness and introduce stochastic effects into the solutions.

PMID- 28741180
TI  - Loss of NHEJ1 Protein Due to a Novel Splice Site Mutation in a Family Presenting
      with Combined Immunodeficiency, Microcephaly, and Growth Retardation and
      Literature Review.
AB  - INTRODUCTION: Non-homologous end joining gene 1 (NHEJ1) defect is a rare form of
      primary immune deficiency. Very few cases have been described from around the
      world. PURPOSE: We are reporting the first family from the Arabian Gulf with
      three siblings presenting with combined immunodeficiency (CID), microcephaly, and
      growth retardation due to a novel NHEJ1 splice site mutation, in addition to a
      review of the previously published literature on this subject. METHODS: Patients'
      clinical, immunological, and laboratory features were examined. Samples were
      subjected to targeted next-generation sequencing (NGS). The pathogenic change in
      NHEJ1 was confirmed by Sanger sequencing, then further assessed at the RNA and
      protein levels. RESULTS: Patients were found to have a homozygous splice site
      mutation immediately downstream of exon 3 in NHEJ1 (c.390 + 1G > C). This led to
      two distinct mRNA products, one of which demonstrated skipping of the last 69
      basepairs (bp) of exon 3 while the other showed complete skipping of the entire
      exon. Although both deletions were in-frame, immunoblotting did not reveal any
      NHEJ1 protein products in patient cells, indicating a null phenotype. CONCLUSION:
      Patients presenting with CID, microcephaly, and growth retardation should be
      screened for NHEJ1 gene mutations. We discuss our data in the context of one of
      our patients who is still alive at the age of 30 years, without transplantation,
      and who is the longest known survivor of this disease.

PMID- 28741181
TI  - Reply to "Surgical treatment of posterior inferior cerebellar artery aneurysms".

PMID- 28741182
TI  - Surgical treatment of posterior inferior cerebellar artery aneurysms.

PMID- 28741183
TI  - Reproduction, ageing, and longevity in two species of laboratory rodents with
      different life histories.
AB  - Social subterranean rodents of the Bathyergidae family are known to have extended
      longevity and some signs of negligible senescence, although the manifestation of
      these traits depends on the reproductive status of individuals. Such enormous
      life history peculiarities are usually explained by the specificity of a
      subterranean way of life. If so, all subterranean rodents, regardless of their
      taxonomic position, are expected to have higher maximum lifespans and shorter
      senescence periods than the related above-ground species. In this study we
      compared the mortality rates and age-related reproductive activity and physical
      conditions in two sympatric rodents of the Cricetidae family: subterranean mole
      voles and above-ground dwarf hamsters. Mole voles have a maximum lifespan that is
      as high as two times the maximum lifespan of the dwarf hamsters; however, only a
      few mole voles outlasted the maximum lifespan of dwarf hamsters. Dwarf hamsters
      were generally more fecund than mole voles, which manifests both in a higher
      number of litters and larger litter sizes. Neither species demonstrated a
      significant age-related decline in litter size or muscle strength, although there
      were negative trends for dwarf hamsters. We conclude that some evidence of
      extended longevity and slow ageing do occur in mole voles, but due to the
      relatively short "subterranean" phylogenetic history of the species, this
      evidence is not as pronounced as in the social species of Bathyergidae family.

PMID- 28741184
TI  - Author's Reply to Candau et al.: Comment on: "How Biomechanical Improvements in
      Running Economy Could Break the 2-Hour Marathon Barrier".

PMID- 28741185
TI  - Comment on: "How Biomechanical Improvements in Running Economy Could Break the 2
      Hour Marathon Barrier".

PMID- 28741187
TI  - [Sexuality education on the Internet : From Dr. Sommer to Dr. Google].
AB  - Female and male adolescents in Germany are increasingly using the Internet to
      find information about sexuality and sexual health. This review paper summarizes
      what we know about the status quo of online sexuality education in Germany.Based
      on a systematic literature review including 40 papers from international, peer
      reviewed journals spanning 2010-2017, this paper first describes different
      aspects of the sexuality-related online search behavior of adolescents: its
      prevalence, predictors, topics and contexts. One main finding is the fact that
      adolescents use a computer or smartphone to type their sexuality-related
      questions into the search engine Google or the search engine of the video
      platform YouTube.Based on 54 online searches, this paper subsequently presents
      the kind of sexuality-related online content adolescents find if they ask "Dr.
      Google" for sexual advice; a collection of 1236 authentic sexuality-related
      questions of adolescents was used for this analysis. It turned out that online
      sexuality education offered by leading professional organizations like the BZgA
      ("Bundeszentrale fur gesundheitliche Aufklarung") or pro familia was nearly
      invisible, while numerous other providers of online sex education consistently
      appeared in the top Google search results. Among them were the "Dr. Sommer" team
      of the youth magazine Bravo; online healthcare and advice portals; online forums;
      the online encyclopedia Wikipedia and, above all, sex education channels on
      YouTube. In this paper, the latter are presented in more detail for the first
      time.The third part of the paper addresses the quality of online sexual education
      over four main areas of quality evaluation. The presentation of the status quo
      ends with some recommendations both for future research and for sexuality
      education in practice.

PMID- 28741186
TI  - Effects of Caffeine Supplementation on Performance in Ball Games.
AB  - Although a large body of evidence exists documenting the ergogenic properties of
      caffeine, most studies have focused on endurance performance. However, findings
      from endurance sports cannot be generalized to performance in ball games where,
      apart from having a high level of endurance, successful athletic performances
      require a combination of physiological, technical and cognitive capabilities. The
      purpose of this review was to critically evaluate studies that have examined the
      effect of a single dose of caffeine in isolation on one or more of the following
      performance measures: total distance, sprint performance, agility, vertical jump
      performance and accuracy in ball games. Searches of three major databases
      resulted in 19 studies (invasion games: 13; net-barrier games: 6) that evaluated
      the acute effects of caffeine on human participants, provided the caffeine dose
      administered, and included a ball games specific task or simulated match.
      Improvements in sprint performance were observed in 8 of 10 studies (80%), and
      vertical jump in 7 of 8 studies (88%). Equivocal results were reported for
      distance covered, agility and accuracy. Minor side effects were reported in 4 of
      19 studies reviewed. Pre-exercise caffeine ingestion between 3.0 and 6.0 mg/kg of
      body mass appears to be a safe ergogenic aid for athletes in ball games. However,
      the efficacy of caffeine varies depending on various factors, including, but not
      limited to, the nature of the game, physical status and caffeine habituation.
      More research is warranted to clarify the effects of caffeine on performance
      measures unique to ball games, such as agility and accuracy. It is essential that
      athletes, coaches and practitioners evaluate the risk-benefit ratio of caffeine
      ingestion strategies on an individual case-by-case basis.

PMID- 28741188
TI  - [Sexually transmitted infections in Germany : The current epidemiological
      situation].
AB  - Sexually transmitted infections (STIs) can impair sexual health. Surveillance and
      study data were used to provide an overview over STIs in Germany. We estimated
      3900 new HIV diagnoses in 2015. Of newly diagnosed infections, 57% were
      attributed to men who have sex with men (MSM). It was further estimated that
      there were 3200 new HIV infections and 84,700 people living with HIV in 2015. A
      total of 6834 syphilis infections were recorded in 2015, which corresponds to an
      increase of 149% since 2009. The incidence in men was 16-times higher than in
      women. Of syphilis infections, 85% could be attributed to MSM. Antimicrobial
      resistance of gonococci against the broad-spectrum antibiotic cefixime decreased
      between 2014 and 2016 after a change of therapy guidelines and remained stable on
      a low level regarding the antibiotic ceftriaxone. After an increase of resistance
      against the antibiotic azithromycin to 11.3% in 2015, we observed a decreasing
      trend in 2016. Between 2013 and 2015, 2,355,336 chlamydia tests were reported
      through the chlamydia sentinel network. Of these, 92.5% of samples were from
      women. Uptake for screening for women <25 years was 11.3% in 2015, with 5.0%
      positive chlamydia tests. In a cross-sectional study among women aged 20-25
      years, a prevalence of human papilloma virus (HPV) of 38.1% was observed. A total
      of 30.5% of 15-year-old women were vaccinated against HPV in 2014. Data suggest
      that STIs represent a high burden of disease. Knowledge of STI prevention should
      be improved by targeted education campaigns. Extending existing offers for
      counselling and testing through cooperation between different health sectors
      would improve early diagnosis and treatment of STIs.

PMID- 28741189
TI  - [Sexting as a risk? : On consensual and non-consensual distribution of personal
      erotic pictures using digital media].
AB  - BACKGROUND: Digital media are used for the purpose of various sexual experiences.
      In recent years the exchange of erotic text messages or images ("sexting") has
      gained the attention of academic research and has increasingly been the center of
      public discussion on sexual boundary violations and violence via digital media.
      The unwanted forwarding of images to a third party is especially relevant in this
      respect. In contrast to media reports about sexting as a risk behavior with
      serious consequences, there is little empirical analysis about the actual sexting
      practice of adolescents and adults in Germany. OBJECTIVE: This paper is the first
      to describe sexting behavior of young adults in Germany on the basis of a large
      representative student sample. MATERIAL AND METHODS: Data were collected in 2012
      in the course of a nationwide study. Students from 15 universities were asked
      among other things about their experiences with sending erotic text messages or
      images, the non-consensual forwarding of images and its consequences. RESULTS:
      More than half of the student sample reported sending erotic text messages, 26.8%
      of women and 16.8% of men had sent erotic images to someone, in most cases to
      their partner. Of the sexters, 2% mentioned that their images had been forwarded
      to another person without their consent. CONCLUSION: The results indicate that in
      Germany sexting is mostly practiced in the context of a romantic relationship.
      Only a small percentage experience unwanted forwarding of images, and negative
      consequences are not reported for all incidents; however, this does not
      relativize the impact of those events implicating serious negative consequences
      for the involved person.

PMID- 28741190
TI  - [Data on the sexual health of providers and clients of sexual services for men
      who have sex with men in Germany].
AB  - Little is known about the sexual health of male providers and clients of
      transactional sex. The data of participants of the European MSM Internet Survey
      (EMIS-DE; N = 50,086) who live in Germany were analysed. The outcomes were
      testing for and diagnoses of HIV and other sexually transmitted infections
      (STIs), partner numbers, illicit drug use, and sexual happiness in two
      populations: (1) men who offered and (2) men who paid for transactional sex in
      the past 12 months.In the age group of under 30 years (n = 19,138), providers of
      sexual services (escorts) were compared with non-providers; in the age group of
      30 years and above (n = 30,948), we compared men who paid for sexual services
      with those who did not. We applied univariable and multinomial, multivariable
      logistic regression analyses in both age groups.Of those under the age of 30, 8%
      (n = 1529) had been paid for sex in the last 12 months, of which 49% were only
      paid once or twice. Escorts had lower educational achievements, lived more
      commonly in large cities, were more often born abroad, self-defined less
      frequently as gay, and were more frequently single. They reported higher numbers
      of sex partners, more drug use, and more sexual happiness. Escorts were more
      frequently tested for HIV and STIs, and among the tested, more diagnoses of HIV
      and STIs were reported, but those with HIV were less likely to be treated.Among
      those over 30 years, 11% (n = 3334) had paid for sex, the majority (58%) only
      once or twice. Payers were older, lived more commonly in large cities, and were
      more likely to be single, bisexual, or living with a woman. Clients used more
      illicit drugs, sexual enhancement drugs, and sedatives, but reported less sexual
      happiness. They were less likely to be tested for HIV and STIs.

PMID- 28741191
TI  - Systematic Review and Meta-Analysis of Epidural Analgesia Versus Different
      Analgesic Regimes Following Oesophagogastric Resection.
AB  - INTRODUCTION: Effective analgesia following open oesophagogastric (OG) resection
      is considered a key determinant of recovery. This review aimed to compare
      epidural to alternative analgesic techniques in patients undergoing major open
      resection for OG cancer. METHODS: A systematic review and meta-analysis was
      conducted of randomized controlled trials comparing epidural with alternative
      analgesic methods in open OG surgery. Primary outcome was the overall post
      operative morbidity rate. Secondary outcomes included pulmonary complication
      rates, length of stay (LOS) and pain scores at 24 h. RESULTS: Six trials which
      comprised of 249 patients were identified (3 following gastrectomy and 3
      following oesophagectomy). Following gastrectomy, secondary outcomes including
      pulmonary complications and dynamic pain scores at 24 h were improved in the
      epidural groups. No difference was observed in overall morbidity rates or LOS.
      Following oesophagectomy, overall morbidity rates were not reported at all. LOS
      was not shortened, and rest pain was not significantly different in the epidural
      group, but dynamic pain scores were reported to be improved. CONCLUSION: Few
      trials of analgesic regimen have been performed following open OG resection. In
      those trials that have been performed, epidural analgesia has not been shown to
      reduce overall morbidity. Epidural is associated with reduced pulmonary
      complications after gastrectomy, but no benefit has been shown after
      oesophagectomy. Whilst widespread investigation of minimally invasive OG
      techniques currently takes place, it is clear that the most effective patient
      pathway following open OG surgery, particularly oesophagectomy, is still not
      proven. Further trials are required.

PMID- 28741192
TI  - Parastomal Hernia Repair with a 3D Funnel Intraperitoneal Mesh Device and Same
      Sided Stoma Relocation: Results of 56 Cases.
AB  - BACKGROUND: Parastomal hernias (PSHs) are a common and challenging issue. In
      previous studies, three-dimensional (3D) funnel mesh devices have been used
      successfully for the repair of PSHs. METHODS: We performed an analysis of
      prospectively collected data of patients who underwent a same-sided stoma
      reposition with 3D funnel-shaped mesh augmentation in intraperitoneal (IPOM)
      position at our department between the years of 2012 and 2015. Primary outcome
      parameters were intra- and postoperative surgical complications and recurrence
      rate during the follow-up period. RESULTS: Fifty-six patients could be included
      in this analysis. PSH repair was performed in 89.3% as elective surgery and in
      73% in laparoscopic technique. A concomitant incisional hernia (EHS type 2 and 4)
      was found in 50% and repaired in a single-step procedure with PSH. Major
      postoperative complications requiring redo surgery (Clavien-Dindo >=3b) were
      identified in 8.9% (5/56). Overall recurrence rate was 12.5% (7/56). Median
      follow-up time was 38 months, and a 1-year follow-up rate of 96.4% was reached.
      CONCLUSION: PSH repair with 3D funnel mesh in IPOM technique is safe, efficient
      and easy to perform in laparoscopic and open surgical approaches providing
      advantageous results compared to other techniques. Furthermore, simultaneous
      detection and treatment of concomitant incisional hernias has shown favorable.
      However, the mesh funnel distends and becomes shortened encasing a bulky bowel
      mesentery and further shrinkage happens eccentric. Changing mesh construction
      according to lengthening the funnel could possibly lead to reduction in
      recurrence.

PMID- 28741193
TI  - Burr-Hole Craniostomy for Chronic Subdural Hematomas by General Surgeons in Rural
      Kenya.
AB  - INTRODUCTION: Chronic subdural hematoma (cSDH) is a common condition that causes
      significant morbidity and mortality. In rural sub-Saharan Africa, there are very
      few neurosurgeons. Yet, cSDH is treatable by relatively simple surgical
      intervention with potential for rapid clinical improvement. METHODS: We conducted
      a retrospective chart review of all patients with cSDH who underwent burr-hole
      trephination at Tenwek Hospital, Kenya, between July 2014 and July 2016. We
      extracted and compared the clinical presentation, risk factors, operative
      details, and outcomes. RESULTS: A total of 119 patients were identified with a
      mean age of 61.3 years. The majority were men (80%). The main predisposing
      factors were trauma (54.6%) and alcohol intake (34.4%). Patients were generally
      managed with two burr-holes, irrigation, and a subdural drain, remaining for a
      median of 2 days. Operations were assisted by general surgery residents under
      direct supervision of senior residents (46), general surgeons (65), and
      neurosurgeons (8). Complications included recurrence (5.2%), subdural empyema
      (2.5%), postoperative seizures (3.4%), and mortality (6.7%). Improvement of
      symptoms was noted in 91% of all patients. CONCLUSION: Operative management of
      cSDH can be safely performed in rural facilities by general surgeons familiar
      with the procedure and with the institutional resources. The majority of patients
      had satisfactory outcomes.

PMID- 28741194
TI  - The Pathophysiological Basis and Surgical Management of Ranula are Established.

PMID- 28741195
TI  - Comparison of Prognostic Abilities Among Preoperative Laboratory Data Indices in
      Patients with Resectable Gastric and Esophagogastric Junction Adenocarcinoma.
AB  - BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio
      (PLR), lymphocyte-to-monocyte ratio (LMR), modified Glasgow prognostic score
      (mGPS) and prognostic nutritional index (PNI) are simple indices determined
      employing laboratory data alone and have been used to predict the clinical
      outcomes of patients with esophagogastric tumors. However, prior results were
      generally based on analyzing dichotomous data with arbitrary cutoff values. This
      retrospective study aims to assess prognostic utilities of preoperative NLR, PLR,
      LMR, mGPS and PNI, as continuous variables, in gastric cancer (GC) and
      adenocarcinoma of esophagogastric junction (AEG). METHODS: Preoperative data from
      1363 patients who underwent surgery for GC/AEG were retrospectively examined.
      Survival time was evaluated applying the Cox proportional hazard model to both
      univariate and multivariate estimates of clinicopathological factors and the
      aforementioned indices as continuous variables. RESULTS: Preoperatively, each
      index value was significantly associated with T and N stages, as well as
      lymphatic involvement and venous involvement. On univariate Cox regression
      analysis, preoperative NLR, PLR, LMR and PNI were significantly associated with
      overall survival (OS) and relapse-free survival (RFS). Preoperative mGPS was
      associated only with RFS. On multivariate Cox regression analysis, preoperative
      PNI was independently associated with OS and RFS (hazard ratio [HR] 0.62 per 10
      unit increase, 95% CI 0.47-0.82, p < 0.001; HR 0.60, 95% CI 0.46-0.78, p < 0.001,
      respectively), as age, gender, tumor location, T and N stages and venous
      involvement, while other indices lost independence on multivariate analysis.
      CONCLUSIONS: Preoperative PNI, a score related to nutritional status, is of
      importance for predicting long-term outcomes in patients with GC and AEG.

PMID- 28741196
TI  - How Safe is Performing Cholecystectomy in the Oldest Old? A 15-year Retrospective
      Study from a Single Institution.
AB  - BACKGROUND: Globally, the number of people aged 80 years or over, the "oldest
      old," is the fastest growing population group. Because of the strong association
      between age and gallstone disease, both prevalence and incidence of this disease
      are increasing. The feasibility of the cholecystectomy in octogenarians has been
      evaluated in several studies that confirmed the safety of the operation. However,
      the safety of this procedure in nonagenarians is still controversial. The aim of
      this study was to evaluate the safety of cholecystectomies in nonagenarians and
      identify related predictors for postoperative hospital length of stay (LOS) and
      in-hospital mortality up to 30 days postoperatively. METHODS: More than 500
      cholecystectomies, both open and laparoscopic, were performed between January
      2000 and September 2015 at our institution in patients 80 years and older. These
      statistics include both elective and emergent admissions. A retrospective review
      of charts over the last 15 years was conducted to compare mortality and length of
      postoperative stay among two patient groups: 319 octogenarians and 36
      nonagenarians. Parameters evaluated include demographics, surgical presentation,
      American Society of Anesthesiologists (ASA) score, main diagnosis, comorbidities,
      type of surgery performed, LOS and in-hospital mortality. All data were analyzed
      with STATA (v.13) software, using a multivariate logistic regression after
      determining the statistically significant variables through a stepwise
      regression. CONCLUSIONS: We found out that being nonagenarian, compared to
      octogenarian, is not a significant risk factor in terms of LOS and in-hospital
      mortality within 30 days postoperatively. Despite that, the mortality rate among
      nonagenarians is still remarkably high as almost every patient was admitted in an
      emergent setting. The most remarkable predictor for mortality among the two
      groups was an "afternoon/night emergency" surgical presentation (OR 25.5, CI 1.53
      42.35, p = 0.02). Thus, the surgical emergency management for gallbladder disease
      at our institution should be critically reevaluated. Performing the procedure in
      laparoscopy predicted a significant reduction (-5 days, CI -8.5 to -1.4, p =
      0.006) of LOS, while presenting with "gallbladder and bile duct stones" (+6.3
      days, CI 1.5-11.1, p = 0.01) or "acalculous cholecystitis" (+4.7 days, CI 0.4
      9.2, p = 0.03) had the opposite effect. Despite the remarkable mortality rate of
      our series, being nonagenarian should not be considered as a reason to avoid
      gallbladder surgery in case of need. Our study suggests that nonagenarians are
      more suitable surgical candidates than may have previously expected.

PMID- 28741197
TI  - Axillobifemoral Bypasses: Reappraisal of an Extra-Anatomic Bypass by Analysis of
      Results and Prognostic Factors.
AB  - BACKGROUND: Axillobifemoral bypass (AFB) is method of second choice. It is
      reserved for patients at high operative risk or to bypass infected vessels or
      grafts. In this study, we analyzed prognostic factors for AFB patency and limb
      salvage rate to facilitate the choice of procedure. METHODS: Between Jan 2006 and
      Aug 2013, 45 patients underwent AFB surgery in our department, 24 for critical
      limb ischemia (CLI) and 23 for infection. Endpoints of study were graft
      occlusion, graft infection, amputation and patient's death. Prognostic factors
      were compared by univariate analysis for each indication group. Mean follow-up
      was 40.2 (+/-23.2) months. RESULTS: Complication rate was significantly higher in
      infection group (88.0 vs. 54.4%, p = 0.003) and in emergency surgery (83.3 vs.
      56.9%, p = 0.023). Overall primary patency rate after AFB procedures was 66.7%
      after 1, 3, and 5 years, while secondary patency rate was 91.1% after 1 year,
      82.2% after 3 years and 80.0% after 5 years. The primary and secondary patency
      rates did not significantly differ between the both groups (p = 0.059 and p =
      0.136). Following prognostic factors showed a statistically significant influence
      on patency rates in CLI group: >1 previous vascular surgical intervention, patch
      angioplasty at the distal anastomosis site, complications after previous vascular
      surgery, and perioperative intake of platelet aggregation inhibitor. Only the
      employed bypass material had a statistical significant influence on the secondary
      patency rates in the infection group. Overall limb salvage rate was 82.2% after 1
      year, 80.0% after 3 years and 77.8% after 5 years. There were statistically
      significant differences in the limb salvage rates depending on emergency surgery
      and a 3-vessel-run-off in the lower leg in both indication groups. CONCLUSION:
      AFB have acceptable patency and limb salvage rates. AFB is a good alternative in
      patients with CLI at high operative risk or with infections of aortoiliac
      segments, even with endovascular approaches. They remain essential tools in
      vascular surgeon's repertoire.

PMID- 28741198
TI  - Significance of Body Mass Index for Postoperative Outcomes after Lung Cancer
      Surgery in Elderly Patients.
AB  - BACKGROUND: Although the frequency of elderly patients undergoing surgery for
      lung cancer has been increasing, indications for surgery in elderly patients are
      still controversial. Low body mass index is a significant predictor of poor
      prognosis in elderly patients with various medical conditions. Then, we examined
      the long-term outcome of elderly patients who had undergone thoracic surgery for
      lung cancer, focusing especially on body mass index. PATIENTS AND METHODS:
      Between January 2004 and March 2011, 1673 patients with lung cancer underwent
      surgical resection at our institution. Among these patients, we retrospectively
      examined 158 patients aged 80 years or older. RESULTS: Perioperative morbidity
      and mortality rates were 41.8 and 1.3%, respectively. Among 149 patients who were
      completely followed up, 80 patients (53.7%) died. The overall postoperative
      survival rates at 3 and 5 years were 66.9 and 49.9%, respectively. Univariate
      analysis demonstrated that sex (female), smoking index (pack-years <20),
      histology (non-squamous cell carcinoma), pathological stage (stage I) and BMI
      (within normal BMI) were statistically significant factors associated with better
      outcome. Multivariate analysis revealed that patients with a low (<18.5 kg/m2) or
      high (>=25 kg/m2) body mass index had a significantly and poorer prognosis than
      patients with a normal body mass index. CONCLUSION: Body mass index is a more
      useful prognostic factor than other clinical factors including pathological stage
      in elderly patients. Because elderly patients with low and high body mass index
      have a significant poor prognosis, surgeons and pulmonologist should take this
      into account when consider surgical indication for such elderly patients.

PMID- 28741199
TI  - Radioactive Iodine Ablation Decrease Recurrences in Papillary Thyroid
      Microcarcinoma with Lateral Lymph Node Metastasis in Chinese Patients.
AB  - INTRODUCTION: We aimed to carry out a retrospective study from a single
      institution to determine whether radioactive iodine (RAI) ablation decreases the
      risk of recurrence of papillary thyroid microcarcinoma (PTMC) patients that
      presented with lateral lymph node metastasis (LLNM). METHODS: We retrospectively
      analyzed a total of 6361 consecutive PTMC patients who initially underwent
      surgery for the treatment of thyroid carcinoma at the First Hospital of Jilin
      University, between January 2005 and February 2015. Altogether, 137 patients with
      PTMC with LLNM have been enrolled in our study. RESULTS: The disease-free
      survival period was significantly shorter for the RAI (-) patients than for the
      RAI (+) patients (p = 0.0074 by the log-rank test). The disease-free survival
      rates at 5 and 10 years were 93.02 and 87.5%, respectively, in the RAI (-) group
      and 100 and 96.81%, respectively, in the RAI (+) group. CLNM ratio and LLNM ratio
      were factors identified for multivariate analysis by Cox's proportional hazards
      method yielding risk ratios of 7.281 [CI 1.804-17.554; p = 0.010] and 1.157 [CI
      1.0125-9.381; p = 0.048] in the RAI (-) group. CONCLUSION: Taken together, RAI
      may be beneficial for PTMC with LLNM, especially when CLNM ratio or LLNM ratio
      was greater than 0.5.

PMID- 28741200
TI  - Short- and Long-Term Outcomes in Malnourished Patients After Laparoscopic or Open
      Radical Gastrectomy.
AB  - OBJECTIVE: The aim of this study was to compare the short- and long-term outcomes
      of malnourished gastric cancer patients who underwent laparoscopic or open
      radical gastrectomy. BACKGROUND: Preoperative malnutrition is an independent risk
      factor for postoperative mortality and morbidity in major gastrointestinal
      surgery. However, whether laparoscopic surgery can improve the short- and long
      term outcomes of malnourished gastric cancer patients has not been determined.
      METHODS: We reviewed prospectively collected data from 2441 patients with gastric
      cancer between January 2009 and December 2014 and compared the short- and long
      term outcomes in malnourished gastric cancer patients who underwent laparoscopic
      or open radical gastrectomy. Nutritional risk factors included weight loss >10%
      within 6 months, body mass index <18.5 kg/m2, Subjective Global Assessment Grade
      C, and serum albumin <3.0 g/dL. RESULTS: Overall, 501 patients (20.52%) were
      classified as malnourished. Patients with gastric stump carcinoma, neoadjuvant
      chemotherapy, distant metastases, palliative operation, or the presence of other
      malignancies were excluded. Finally, a total of 412 patients were analyzed; 304
      in the laparoscopic group and 108 in the open group. There were no significant
      differences between the two groups regarding the clinicopathological
      characteristics. However, the operation time (181 +/- 53 vs. 253 +/- 81 min),
      intraoperative blood loss (80 +/- 116 vs. 322 +/- 502 mL), time to first
      ambulation (2.21 +/- 1.04 vs. 2.55 +/- 1.50 days), liquid diet (4.91 +/- 1.61 vs.
      5.72 +/- 2.09 days) and semiliquid diet (7.67 +/- 1.56 vs. 9.53 +/- 2.09 days) as
      well as the postoperative hospital stay duration (13.00 +/- 6.56 vs. 15.22 +/-
      6.87 days) were significantly lower in the laparoscopic group than those in the
      open group (p < 0.05). The instances of overall complications (laparoscopic vs.
      open: 18.4 vs. 30.6%, p = 0.008) and pneumonia (laparoscopic vs. open: 10.9 vs.
      19.4%, p = 0.023) were significantly lower in the laparoscopic group. With a
      median follow-up of 31.0 months (range 1.0-88.0), the 3-year overall survival
      (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) rates
      for the entire cohort were 58.9, 54.0 and 63.0%, respectively. Further analysis
      showed that the OS (57.5 vs. 59.4%, p = 0.560), RFS (51.8 vs. 54.8%, p = 0.441)
      and CSS (62.8 vs. 63.0%, p = 0.789) between the laparoscopic and open groups,
      respectively, were no significantly different. Further analysis showed no
      significant differences in the OS rates of the two groups of patients stratified
      by tumor stage (p > 0.05). CONCLUSION: Compared with open radical gastrectomy,
      laparoscopy would reduce the postoperative complications especially pneumonia and
      shorten the postoperative hospital stay for patients with preoperative
      malnutrition without affecting their long-term survival.

PMID- 28741201
TI  - Cost-Effectiveness of a Locally Organized Surgical Outreach Mission: Making a
      Case for Strengthening Local Non-Governmental Organizations.
AB  - INTRODUCTION: Many low- and middle-income countries (LMICs) have a high
      prevalence of unmet surgical need. Provision of operations through surgical
      outreach missions, mostly led by foreign organizations, offers a way to address
      the problem. We sought to assess the cost-effectiveness of surgical outreach
      missions provided by a wholly local organization in Ghana to highlight the role
      local groups might play in reducing the unmet surgical need of their communities.
      METHODS: We calculated the disability-adjusted life years (DALY) averted by
      surgical outreach mission activities of ApriDec Medical Outreach Group (AMOG), a
      Ghanaian non-governmental organization. The total cost of their activities was
      also calculated. Conclusions about cost-effectiveness were made according to
      World Health Organization (WHO)-suggested parameters. RESULTS: We analyzed 2008
      patients who had been operated upon by AMOG since December 2011. Operations
      performed included hernia repairs (824 patients, 41%) and excision biopsy of soft
      tissue masses (364 patients, 18%). More specialized operations included
      thyroidectomy (103 patients, 5.1%), urological procedures (including
      prostatectomy) (71 patients, 3.5%), and plastic surgery (26 patients, 1.3%).
      Total cost of the outreach trips was $283,762, and 2079 DALY were averted; cost
      per DALY averted was 136.49 USD. The mission trips were "very cost-effective" per
      WHO parameters. There was a trend toward a lower cost per DALY averted with
      subsequent outreach trips organized by AMOG. CONCLUSION: Our findings suggest
      that providing surgical services through wholly local surgical mission trips to
      underserved LMIC communities might represent a cost-effective and viable option
      for countries seeking to reduce the growing unmet surgical needs of their
      populations.

PMID- 28741202
TI  - A user-centred approach to developing bWell, a mobile app for arm and shoulder
      exercises after breast cancer treatment.
AB  - PURPOSE: The study aim was to develop a mobile application (app) supported by
      user preferences to optimise self-management of arm and shoulder exercises for
      upper-limb dysfunction (ULD) after breast cancer treatment. METHODS: Focus groups
      with breast cancer patients were held to identify user needs and requirements.
      Behaviour change techniques were explored by researchers and discussed during the
      focus groups. Concepts for content were identified by thematic analysis. A rapid
      review was conducted to inform the exercise programme. Preliminary testing was
      carried out to obtain user feedback from breast cancer patients who used the app
      for 8 weeks post surgery. RESULTS: Breast cancer patients' experiences with ULD
      and exercise advice and routines varied widely. They identified and prioritised
      several app features: tailored information, video demonstrations of the
      exercises, push notifications, and tracking and progress features. An evidence
      based programme was developed with a physiotherapist with progressive exercises
      for passive and active mobilisation, stretching and strengthening. The exercise
      demonstration videos were filmed with a breast cancer patient. Early user testing
      demonstrated ease of use, and clear and motivating app content. CONCLUSIONS:
      bWell, a novel app for arm and shoulder exercises, was developed by breast cancer
      patients, health care professionals and academics. Further research is warranted
      to confirm its clinical effectiveness. IMPLICATIONS FOR CANCER SURVIVORS: Mobile
      health has great potential to provide patients with information specific to their
      needs. bWell is a promising way to support breast cancer patients with exercise
      routines after treatment and may improve future self-management of clinical care.

PMID- 28741203
TI  - Flow cytometric characterization of bacterial abundance and physiological status
      in a nitrifying-denitrifying activated sludge system treating landfill leachate.
AB  - Flow cytometry has recently been presented as a research tool in the assessment
      of the viability/activity of activated sludge from municipal wastewater treatment
      plants, but it has not put in practice for industrial biotreatments yet. In this
      study, for the first time ever, the reliability and significance of the
      multiparameter flow cytometry applied to the biological nitrification
      denitrification treatment of leachate have been evaluated. Using a double
      staining procedure (cFDA/PI), the viable, damaged, and dead subpopulations were
      determined, and the results were compared to those obtained with conventional
      methods, such as nitrogen and oxygen uptake rates or plate counting. Flow
      cytometry showed that viable cells represented approximately 47% of the total
      population, whereas active cells accounted for 90%. For both sludge from
      nitrification and denitrification processes, with less than 1% of them being also
      culturable in plate. Either flow cytometry or uptake rates revealed that health
      status of sludge remained constant throughout the biotreatment, which is
      consistent with the high recirculation rates. Under anaerobic starvation
      conditions, physiological status of sludge remained constant as well as specific
      oxygen and denitrification rates. Nevertheless, both the culturability in plate
      and the nitrification rate significantly decreased. These findings proved that
      multiparameter flow cytometry is a useful tool for the assessment of the
      viability and activity of sludge from a nitrification-denitrification
      biotreatment process. These results gathered all the bacterial communities in the
      sludge, so the decay in minority populations, such as nitrifying bacteria,
      requires the use of a complementary technique to evaluate specific activities.

PMID- 28741204
TI  - Remarks on the current quality of groundwater in Vietnam.
AB  - This paper reviews the current quality of groundwater in Vietnam. In Vietnam,
      groundwater is obtained primarily from tubewells, which have high concentrations
      of pollutants such as As, Fe, Mn, and NH4+. In the areas where groundwater tests
      were conducted, arsenic levels ranged from 0.1-3050 MUg/L, which substantially
      exceed the standard of 10 MUg/L which has been established by the WHO.
      Contamination sources are distributed over a large area from the Red River Delta
      in the north to the Mekong River Delta in the south, putting as many as ten
      million people at risk of adverse health effects. Levels of arsenic and iron in
      sediment are strongly correlated, which indicate that the presence of arsenic in
      groundwater results from the reduction of arsenic bound to iron oxyhydroxides. It
      is important to raise awareness of these issues among the Vietnamese public by
      disseminating information about the negative effects of contaminated drinking
      water, as well as carrying out long-term research projects to identify other
      sources of contamination and improving water treatment technology and water
      management capabilities.

PMID- 28741205
TI  - One more step toward a push-pull strategy combining both a trap crop and plant
      volatile organic compounds against the cabbage root fly Delia radicum.
AB  - The "push-pull" strategy aims at manipulating insect pest behavior using a
      combination of attractive and repulsive stimuli using either plants derived
      volatile organic compounds or insect host plant preferences. In a field
      experiment using broccoli as a crop, we combined in a "push-pull" context the
      oviposition deterrent effect of dimethyl disulfide and the attractive effect of a
      Chinese cabbage strip enhanced with Z-3-hexenyl-acetate. The push component
      dimethyl disulfide reduced Delia radicum L. (Diptera: Anthomyiidae) oviposition
      on broccoli by nearly 30%, and applying Z-3-hexenyl-acetate in the pull component
      of Chinese cabbage increased it by 40%. Moreover, pest infestation was 40% higher
      in Chinese cabbage compared to broccoli and parasitism by Trybliographa rapae
      Westwood (Hymenoptera: Figitidae) was four times higher on this trap plant. In
      addition, lab experiments confirmed that Chinese cabbage is a more suitable host
      plant than broccoli for the cabbage root fly. Taken together, our results
      demonstrate the technical possibility of using a push-pull strategy to manipulate
      the egg-laying behavior of D. radicum in the field.

PMID- 28741206
TI  - Isolation of limonoid compound (Hamisonine) from endophytic fungi Penicillium
      oxalicum LA-1 (KX622790) of Limonia acidissima L. for its larvicidal efficacy
      against LF vector, Culex quinquefasciatus (Diptera: Culicidae).
AB  - Upon screening for novel and potential biocompounds with larvicidal activities,
      we successfully isolated hamisonine (HMSN) a limonoid compound from endophytic
      fungi Penicillium oxalicum LA-1 of Limonia acidissima. The extracted compound
      structure was elucidated by spectral studies such as UV-vis spectroscopy, thin
      layer chromatography, FTIR, LC-ESI-MS, 1H NMR, and 13C NMR upon comparing with
      the spectral data available in the literature. Further, the isolated HMSN was
      tested against III and IV instar Culex quinquefasciatus larvae. The outcome of
      this study clearly emphasize that the extracted compound HMSN possesses a
      stupendous larvicidal activity in a dose-dependent manner with the LC50 and LC90
      values of 1.779 and 7.685 ppm against III instar larvae and 3.031 and 28.498 ppm
      against IV instar larvae of C. quinquefasciatus, respectively. Interestingly, the
      histological studies evidently showing the damage of peritrophic membrane and
      epithelial cells of testing mosquito larvae.

PMID- 28741207
TI  - Evaluation of colour temperatures in the cultivation of Dunaliella salina and
      Nannochloropsis oculata in the production of lipids and carbohydrates.
AB  - The production of biofuels from microalgae is a promising and sustainable
      alternative. Its production is determined by the content of lipids and
      carbohydrates, which is different for each microalgae species and is affected by
      environmental factors, being lighting one of the principal determining their
      biochemical composition. The colour temperature (electromagnetic radiation and
      light spectrum) is a determining factor for the production of lipids and
      carbohydrates in microalgae. The aim of this assay was to evaluate the effect of
      three colour temperatures (6500, 10,000 and 20,000  degrees K) on the biomass
      (cel mL-1), biomass production and productivity (g L-1 and g L-1 day-1), lipid
      and carbohydrate content (%), lipid and carbohydrate production and productivity
      (mg L-1 and mg L-1 day-1), composition and content of fatty acids (%) in two
      microalgae species: Dunaliella salina and Nannochloropsis oculata. The highest
      cell density was observed for N. oculata in stationary phase in the control
      (83.93 * 106 cel mL-1). However, higher lipid content was obtained in D. salina
      in stationary phase at 10,000  degrees K (80%), while N. oculata showed 67% at
      6500  degrees K. The highest carbohydrate content was 25% in stationary phase for
      D. salina at 20,000  degrees K. Regarding the production of lipids, D. salina
      reached a maximum of 523 mg L-1 in exponential phase at 6500 and 10,000  degrees
      K. The highest carbohydrate production was 38 mg L-1 for D. salina in exponential
      phase at 20,000  degrees K. In both microalgae, 15 different fatty acids were
      identified; the most abundant was palmitic acid with 35.8% for N. oculata in
      stationary phase at 10,000  degrees K, while D. salina showed 67% of
      polyunsaturated fatty acids in exponential phase at 6500  degrees K. In
      conclusion, the ideal colour temperature for microalgae culture to obtain
      biofuels should be based on the biomolecule of interest, being necessary to
      individually evaluate for each species.

PMID- 28741208
TI  - Short-duration hydrothermal fermentation of food waste: preparation of soil
      conditioner for amending organic-matter-impoverished arable soils.
AB  - Soil conditioners can be used to compensate for the insufficient soil nutrition
      and organic matter (OM) of arable soils. However, the traditional preparation
      method for soil conditioners is lengthy and requires facilities that occupy large
      tracts of land. In this study, a short-duration hydrothermal fermentation (SHF)
      method was developed for the preparation of soil conditioners from food waste.
      The SHF method required only 18 h to produce soil conditioners with
      physicochemical characteristics that were similar to those of soil conditioners
      obtained through traditional fermentation (TF), which takes 20 days to complete.
      Inoculation and dynamic SHF significantly affected the distribution of different
      molecular weight fractions in the prepared soil conditioners. The results of
      spectral analysis revealed that a large amount of soluble microbial byproducts
      and carbohydrate C formed in the SHF soil conditioner. This effect indicated that
      the SHF soil conditioner supplied not only immediately available nutrients, which
      can stimulate the growth of soil microbial communities, but also provided
      sustained-release nutrients for the long-term cultivation of crops on OM
      impoverished soils. Cyanobacteria were present in the SHF soil conditioner at a
      relative abundance of 6.29%, which was 28.6 and 314.5 times those in the raw
      material and TF soil conditioner, respectively. Amending OM-impoverished soil
      with the SHF soil conditioner enhanced the carbon pool management index of the
      resulting SHF soil by 1.50 and 1.12 times those of unfertilized soil and TF soil,
      respectively. These results indicated that the SHF soil exhibited a high capacity
      to supply nutrients for crop growth.

PMID- 28741209
TI  - Pb-induced changes in roots of two cultivated rice cultivars grown in lead
      contaminated soil mediated by smoke.
AB  - Nowadays, public concerns regarding deleterious effect of lead (Pb) is on rise
      due to its abundance and toxic effect on plants and other living organisms. In
      plants, it has no noticeable biological importance but can cause various
      morphological, physiological, and biochemical malfunctions. To evaluate the
      remediating potential of plant-derived smoke (Cymbopogon jwarancusa), a pot
      culture experiment was designed to investigate the physiological, biochemical,
      metabolic, and antioxidant parameters of roots in lead (0 (control), 500, 1000,
      and 1500 ppm)-contaminated soil. Under dark condition, seeds were primed in smoke
      solution with two dilutions (1:500 and 1:1000) for 24 h. With an increasing
      concentration of Pb stress, fresh and dry weight and total nitrogen and protein
      contents decreased significantly while an increase was observed in smoke-treated
      seed. With increasing Pb stress level, metabolites (i.e., proline, total soluble
      sugar, total soluble protein, glycine betaine), and antioxidants (i.e.,
      superoxide dismutase, peroxidase, catalase, ascorbate peroxidase,
      malonyldialdehyde, and H2O2), contents of roots were increased in non-treated
      (without smoke treatment) samples, whereas comparatively, a low level of
      alteration in aforementioned metabolites and antioxidative parameters was
      observed in the seeds treated with smoke solution. These results suggest a
      positive role of smoke in alleviating lead-induced changes in roots of two
      cultivated cultivars of rice grown in Pb-contaminated soil.

PMID- 28741210
TI  - Effects of BPF on steroid hormone homeostasis and gene expression in the
      hypothalamic-pituitary-gonadal axis of zebrafish.
AB  - Bisphenol F (BPF) has been frequently detected in various environmental
      compartments, and previous studies found that BPF exhibits similar estrogenic and
      anti-androgenic effects on the mammalian endocrine system to those of bisphenol A
      (BPA). However, the potential disrupting effects of BPF on aquatic organisms and
      the underling disrupting mechanisms have not been investigated. In this study,
      the potential disrupting mechanisms of BPF on the hypothalamic-pituitary-gonadal
      (HPG) axis and liver were probed by employing the OECD 21-day short-term
      fecundity assay in zebrafish. The results show that BPF exposure (1 mg/L)
      impaired the reproductive function of zebrafish, as exemplified by alterations to
      testicular and ovarian histology of the treated zebrafish. Homogenate
      testosterone (T) levels in male zebrafish decreased in a concentration-dependent
      manner, and 17beta-estradiol (E2) levels increased significantly when fish were
      exposed to 0.1 and 1 mg/L BPF. The real-time polymerase chain reaction was
      performed to examine gene expression in the HPG axis and liver. Hepatic
      vitellogenin expression was significantly upregulated in males, suggesting that
      BPF possesses estrogenic activity. The disturbed hormone balance was enhanced by
      the significant changes in gene expression along the HPG axis. These alterations
      suggest that BPF leads to adverse effects on the endocrine system of teleost
      fish, and that these effects were more prominent in males than in females.

PMID- 28741211
TI  - Influence of pH, EDTA/Fe(II) ratio, and microbial culture on Fe(II)-mediated
      autotrophic denitrification.
AB  - Fe(II)-mediated autotrophic denitrification with four different microbial
      cultures under different pH and EDTA/Fe(II) conditions was investigated in batch
      bioassays. Initially, the highest nitrate removal (72%) was achieved with an
      activated sludge inoculum. The use of pure cultures of Pseudogulbenkiania strain
      2002 and Thiobacillus denitrificans resulted in a 55 and 52% nitrate removal,
      respectively. No denitrification was observed for a mixed culture dominated by
      Thiobacillus thioparus and T. denitrificans. A longer enrichment on Fe(II) and
      the supplementation of thiosulfate as additional electron donor were needed to
      stimulate the denitrifying activity of the Thiobacillus-mixed culture. A second
      subculture on Fe(II) as sole electron donor resulted in higher denitrification
      efficiencies for all microbial cultures. In particular, nitrate removal reached
      up to 84% with a specific nitrate removal rate of 1.160 mM.(g VSS.day)-1 in the
      bioassays seeded with the Thiobacillus-mixed culture. All cultures were favored
      by decreasing the EDTA/Fe(II) molar ratio from 2.0 to 0.5. The most significant
      denitrification enhancement was observed for the Pseudogulbenkiania species,
      indicating a lower tolerance to EDTA. The two pure cultures effectively
      maintained denitrification at pH 7.0 and were more sensitive to a pH decrease.
      Conversely, the optimal pH was 6.0 for the Thiobacillus-mixed and activated
      sludge cultures.

PMID- 28741212
TI  - Influence of orientation, glazing proportion and zone aspect ratio on the thermal
      performance of buildings during the winter period.
AB  - The objective of this study is to assess the effect of orientation, glazing
      proportion and aspect ratio of building zones on heat fluxes through their
      surfaces, under specific environmental conditions. The investigation is carried
      out for thermally-insulated building zones with a varying facade orientation
      corresponding to each cardinal point, during the winter period in the northern
      Greek region. For this purpose, three glazing-to-facade ratios (GR) are taken
      into account; along with the glazing ratio the influence of the glazing U value
      is also considered. Regarding the impact of the fenestration layout geometry,
      five different building aspect ratio profiles are examined. Thermal fluxes are
      assessed for two different indoor temperature settings, while the operation of
      the heating unit is assumed to be continuous. The transient thermal analysis with
      its mathematical formulation and solution are based on the thermal-network
      modelling approach, while the solar heat gain through glazing relies on the
      sunlit-pattern approach; in this way, the stricken by the solar rays glazing area
      is projected onto any interior surfaces to form the so called "sunlit" areas. As
      the orientation, glazing proportion and aspect ratio of the building zone vary,
      so do the sizes and shapes of the illuminated "sunlit" areas. Accordingly, the
      delivered into the zone direct solar energy and its diffused and ground reflected
      components can be determined. The adopted methodology provides a more accurate
      determination of solar heat gain with respect to glazing proportion and
      orientation as well as zone aspect ratio. With regard to surface orientation,
      glazing proportion and aspect ratio, computer results demonstrate the improvement
      of the thermal performance for a building zone with a south oriented glazing
      surface, as well as the deterioration for the other surface orientations;
      relative increases/decreases in the energy fluxes of a rectangular shaped
      building zone compared to a square-shaped building zone can reach up to 50%/100%.

PMID- 28741213
TI  - Geochemical fractionation and pollution assessment of Zn, Cu, and Fe in surface
      sediments from Shadegan Wildlife Refuge, southwest of Iran.
AB  - This research focuses on the fractionation and distribution patterns of heavy
      metals (Zn, Cu, and Fe) in surficial sediments collected from Shadegan Wildlife
      Refuge, the biggest wetland in southern part of Iran, to provide an overall
      classification for the sources of metals in the study area using a sequential
      extraction method. For this purpose, a four-step sequential extraction technique
      was applied to define the partitioning of the metals into different geochemical
      phases of the sediment. The results illustrated that the average total level of
      Zn, Cu, and Fe in surface sediments were 55.20 +/- 16.04, 22.86 +/- 5.68, and
      25,979.01 +/- 6917.91 MUg/g dw, respectively. On the average, the chemical
      partitioning of all metals in most stations was in the order of residual
      >oxidizable-organic > acid-reducible > exchangeable. In the same way, the results
      of calculated geochemical indices revealed that Cu, Zn, and Fe concentrations are
      mainly influenced by lithogenic origins. Compared with consensus-based SQGs, Cu
      was likely to result in occasionally harmful biological effects on the biota.

PMID- 28741214
TI  - Market segmentation and industry overcapacity considering input resources and
      environmental costs through the lens of governmental intervention.
AB  - The problems with China's regional industrial overcapacity are often influenced
      by local governments. This study constructs a framework that includes the
      resource and environmental costs to analyze overcapacity using the non-radial
      direction distance function and the price method to measure industrial capacity
      utilization and market segmentation in 29 provinces in China from 2002 to 2014.
      The empirical analysis of the spatial panel econometric model shows that (1) the
      industrial capacity utilization in China's provinces has a ladder-type
      distribution with a gradual decrease from east to west and there is a severe
      overcapacity in the traditional heavy industry areas; (2) local government
      intervention has serious negative effects on regional industry utilization and
      factor market segmentation more significantly inhibits the utilization rate of
      regional industry than commodity market segmentation; (3) economic openness
      improves the utilization rate of industrial capacity while the internet
      penetration rate and regional environmental management investment have no
      significant impact; and(4) a higher degree of openness and active private
      economic development have a positive spatial spillover effect, while there is a
      significant negative spatial spillover effect from local government intervention
      and industrial structure sophistication. This paper includes the impact of
      resources and the environment in overcapacity evaluations, which should guide
      sustainable development in emerging economies.

PMID- 28741215
TI  - Acute toxicity of chlorpyrifos and carbosulfan to glochidia of the freshwater
      mussel Hyriopsis bialata Simpson, 1900.
AB  - The acute toxicity of carbosulfan and chlorpyrifos in formulated pesticides to
      glochidia (larvae) of the freshwater mussel (Hyriopsis bialata Simpson, 1900) was
      evaluated under static conditions in moderately hard dechlorinated tap water.
      Measured pesticide concentrations were 26 to 34% lower than nominal
      concentrations; therefore, all results are expressed in terms of measured active
      ingredient. Carbosulfan was relatively non-toxic to the mussel larvae with median
      effective concentrations (EC50) of carbosulfan at 24 and 48 h greater than 0.10
      mg/L. The EC50s of chlorpyrifos at 24 and 48 h were 0.083 and 0.078 mg/L,
      respectively (measured concentrations). The 48-h EC50 of a combined exposure to a
      mixture of chlorpyrifos and carbosulfan at a constant ratio of 2.9:1 was
      0.0142:0.049 mg CP:CB/L. In a separate experiment, the effect of water hardness
      on carbosulfan, chlorpyrifos, or a combined exposure was assessed using glochidia
      exposed to either soft, moderately hard, or hard reconstituted water. There was
      no effect of water hardness on the survival of glochidia after 24- or 48-h
      exposure to carbosulfan. The chlorpyrifos 48-h EC50s in soft water, moderately
      hard water, and hard water were 0.18, 0.11, and 0.16 mg/L, respectively. The data
      indicate that the lowest water hardness resulted in the highest survival of
      glochidia, whereas an increase to moderate water hardness resulted in
      significantly decreased survival of glochidia (F = 15.5, P < 0.05). The EC50s of
      a combined exposure at 48 h in soft water, moderately hard water, and hard water
      were 0.124:0.044, 0.132:0.047, and 0.064:0.022 mg CP:CB/L, respectively. The data
      indicate that the combined toxicity was lowest at low and moderate water
      hardness, whereas an increase to high water hardness resulted in a significantly
      decreased survival of glochidia. After 48 h, the toxicity of the combined
      chlorpyrifos and carbosulfan exposure in soft and hard water was greater than
      that of chlorpyrifos alone.

PMID- 28741216
TI  - Epidemiological and outcome data in Japanese patients with deep vein thrombosis
      with and without malignancy.
AB  - There are very few epidemiological studies on Japanese patients with deep vein
      thrombosis (DVT). In particular, mortality rate differences in Japanese DVT
      patients with and without malignancy have rarely been evaluated. To elucidate
      these differences, we enrolled 211 patients who had been diagnosed with de-novo
      acute DVT of the pelvis or lower extremities between January 2012 and December
      2015. The clinical characteristics, treatment information, and follow-up data
      were retrospectively assessed. We compared these variables in patients with (n =
      120) and without (n = 91) concomitant malignancies. The median age of patients
      was 67 years, 33.7% were male, and 82.9% patients were treated with oral
      anticoagulants including direct oral anticoagulants. The clinical characteristics
      and treatment provided were almost identical in the two groups with some
      exceptions. Three-year survival rates of the total population, patients with
      malignancy, and patients without malignancy were 80.6, 67.6, and 97.6%,
      respectively (log-rank p < 0.001). Multivariable Cox regression analysis
      demonstrated that malignancy was independently associated with high risk of 3
      year all-cause mortality with an adjusted hazard ratio of 9.1 (95% confidence
      interval; 2.1-39.0, p = 0.003). Bootstrap validation demonstrated an acceptable
      index corrected slope of 0.766 without significant overfitting in a multivariable
      model. In conclusion, we analyzed epidemiological data on Japanese patients with
      DVT. Malignancy was independently associated with increased 3-year all-cause
      mortality.

PMID- 28741217
TI  - Effects of non-invasive ventilation in patients with acute respiratory failure
      excluding post-extubation respiratory failure, cardiogenic pulmonary edema and
      exacerbation of COPD: a systematic review and meta-analysis.
AB  - BACKGROUND: This meta-analysis compared the effects of non-invasive ventilation
      (NIV) with invasive mechanical ventilation (InMV) and standard oxygen (O2)
      therapy on mortality and rate of tracheal intubation in patients presenting acute
      respiratory failure (ARF). METHODS: We searched the MEDLINE, EMBASE and Cochrane
      Central Register of clinical trials databases between 1949 and May 2015 to
      identify randomized trials of NIV for ARF. We excluded the ARF caused by
      extubation, cardiogenic pulmonary edema, and COPD. RESULTS: The meta-analysis
      included 21 studies and 1691 patients, of whom 846 were assigned to NIV and 845
      to control (InMV or standard O2 therapy). One hundred ninety-one patients (22.6%)
      in the NIV group and 261 patients (30.9%) in the control group died before
      discharge from hospital. The pooled odds ratio (OR) for short-term mortality (in
      hospital mortality) was 0.56 (95% CI 0.40-0.78). When comparing NIV with standard
      O2 therapy, the short-term mortality was 155 (27.4%) versus 204 (36.0%),
      respectively. For this comparison, the pooled OR of short-term mortality was 0.56
      (95% CI 0.36-0.85). When comparing NIV with InMV, the short-term mortality was 36
      (12.9%) versus 57 (20.5%) patients, respectively. For this comparison, the pooled
      OR of short-term mortality was 0.56 (95% CI 0.34-0.90). Tracheal intubation was
      performed in 106 patients (22.7%) in the NIV and in 183 patients (39.4%) in the
      standard O2 group, representing a pooled OR of 0.37 (95% CI 0.25-0.55). There
      were publication biases and the quality of the evidence was graded as low.
      CONCLUSION: Compared with standard O2 therapy or InMV, NIV lowered both the short
      term mortality and the rate of tracheal intubation in patients presenting with
      ARF.

PMID- 28741218
TI  - Asymmetric pedicle subtractionosteotomy (aPSO) guided by a 3D-printed model to
      correct a combined fixed sagittal and coronal imbalance.
AB  - Surgical correction of fixed thoracolumbar deformity is usually achieved by
      estimating the preoperatively planned correction angles during surgery and is
      therefore prone to inaccuracy. This is particularly problematic in biplanar
      deformities. To overcome these difficulties, 3D model for planning, preparation,
      and simulation of an asymmetric pedicle subtraction osteotomy (aPSO) was printed
      and used to realign coronal and sagittal balance in case of rigid degenerative
      kyphoscoliosis. A 59-year-old woman presented with severe back pain and spinal
      claudication and was diagnosed with a rigid kyphoscoliosis with multilevel spinal
      stenosis. Spino-pelvic parameters were measured preoperatively (pelvic incidence
      47 degrees  [PI], lumbar lordosis 18 degrees  [LL]; pelvic tilt 42 degrees  [PT],
      T1 pelvic angle 40 degrees  [TPA], Cobb angle 33 degrees , sagittal vertical axis
      10.5 cm [SVA]). To aid the complex deformity in the sagittal and coronal plane, a
      1:1 3D model of the spine was printed according to the preoperative computed
      tomography (CT). With the use of a rebalancing software, the spine was prepared
      in vitro as a model for intraoperative realignment and the correction was
      preoperatively simulated. Surgery was accomplished according to the preoperative
      software-guided plan. Asymmetric pedicle subtraction osteotomy (aPSO) of L3
      identical to the 3D model was performed. Additionally, a Smith-Peterson osteotomy
      of L4/5 with transforaminal lumbar interbody fusion (TLIF) and laminectomy of L2
      S1 with pedicle screw instrumentation TH12-S1 was accomplished. Postoperative
      radiological parameters revealed good success (LL 40 degrees , SVA 6 cm, PT 19
      degrees , TPA 22 degrees , and a Cobb angle of 8 degrees ). Improvement of the
      Oswestry disability index (ODI) of 42 to 18, the visual analog scale (VAS) of 8
      to 1, and walking distance 100 to 8000 m compared to preoperatively resulted at
      24 months follow-up. The precise coronal and sagittal correction of a rigid
      degenerative kyphoscoliosis presents a major challenge. Asymmetric PSO is able to
      realign the thoracolumbar spine in both the coronal and sagittal planes. The
      creation of an in vitro 3D-printed model of a patient's spinal deformity in
      combination with a software to calculate the correction angles facilitates
      preoperative planning and implementation of aPSO.

PMID- 28741219
TI  - In vitro analysis of platelet function in acute aneurysmal subarachnoid
      haemorrhage.
AB  - Platelet function might play an essential role in the pathogenesis of delayed
      cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Thus,
      impaired platelet function and disturbed primary haemostasis induced by intake of
      acetylsalicylic acid (ASA) might influence the rate of DCI. Primary haemostasis
      and platelet function can be measured with in vitro diagnosis (platelet function
      analyser test, PFA 100). The aim of this study is to evaluate the rate of DCI,
      haemorrhagic complications and the neurological outcome. Two groups were compared
      (patients with regular platelet function versus patients with impaired platelet
      function). This is a retrospective observational study. An initial cohort of 787
      patients with SAH has been treated from January 2005 to September 2012. Seventy
      nine patients (10%) with aneurysmal SAH, a history of ASA medication and PFA
      testing within the first 24 h after aneurysm rupture have been included. The
      overall rate of DCI in the present study was 43%. In vitro platelet function
      testing showed pathological primary haemostasis in 69.6%. The DCI rate was higher
      in patients with regular tested primary haemostasis (p = 0.02, OR = 3.16, 95%CI =
      [1.19; 8.83]). However, outcome assessment by mGOS did not show a significant
      difference between the groups. Patients with impaired primary haemostasis did not
      display a higher rate of haemorrhagic complications. Impairment of primary
      haemostasis resulting from an impairment of platelet function at an early stage
      after SAH might lead to a lower rate of DCI. In vitro testing of platelet
      function might be useful to predict the occurrence of DCI in the course.

PMID- 28741220
TI  - Independent impact of plasma homocysteine levels on neurological outcome
      following head injury.
AB  - Homocysteine (tHcy) has been hardly studied among patients with head injury. This
      study was to evaluate whether there is any independent impact of tHcy levels on
      neurological outcome following head injury in a multivariate model. Patients
      admitted within 24 h of injury were included in the study, along with 20 age- and
      gender-matched controls. Plasma levels of tHcy were measured at admission using
      direct immunoassay. All the variables were analyzed with respect to tHcy levels
      and outcome according to Glasgow Outcome Score (GOS) at 3 months. Univariate and
      multivariate analyses were performed using SPSS 21. There were a total of 72
      patients in the study. tHcy levels were significantly higher after head injury
      (mean 24.03[SD +/- 16.0] MUmol/L), compared to matched controls (mean 16.62 [SD
      +/- 10.4] MUmol/L) (p = 0.05). Patients with severe head injury, acute SDH, or
      diffuse higher radiological grades had greater levels of tHcy compared to others.
      There was a significant relationship between tHcy level and neurological outcome.
      tHcy levels were significantly higher in patients who had unfavorable GOS (mean
      36.22[+/-25.3] MUmol/L), compared to those with favorable GOS (mean 22.71[+/
      14.3] MUmol/L) (P = 0.03). In multivariate analysis, tHcy level (adj. odds ratio
      [OR] 1.17, P = 0.05) and Glasgow Coma Scale (adj. OR 5.17, P = 0.01) had
      significant association with neurological outcome at 3 months independent of age,
      dietary habit, radiological grading and of each other. tHcy level has significant
      independent impact on neurological outcome and may be useful as a prognostic
      marker following head injury.

PMID- 28741221
TI  - Optimization and Application of a Biotinylation Method for Quantification of
      Plasma Membrane Expression of Transporters in Cells.
AB  - Quantitative proteomics, using LC-MS/MS, is increasingly used to quantify drug
      transporters present in tissues and cells. Most of these investigations quantify
      total transporter expression in the cells by utilizing a total membrane fraction,
      not only the plasma membrane. Here, we report development and optimization of a
      biotinylation method to quantify protein expression of transporters in the plasma
      membrane of cells. The Pierce cell surface isolation protocol was optimized for
      plasma membrane isolation. Incubation of OATP1B1-expressing CHO cells with 0.78
      mg/mL of membrane impermeable biotinylation reagent (sulfo-NHS-SS-biotin) at 37
      degrees C for 1 h resulted in optimum isolation of the plasma membrane.
      Subsequently, the expression of transporters in the plasma membrane as a percent
      of the total was determined by quantitative proteomics using LC-MS/MS. Mean (+/
      SD) plasma membrane expression of OATP1B1 in plated OATP1B1-expressing CHO,
      MDCKII, and HEK293 cells was found to be 79.7% (+/-4.7%), 67.7% (+/-12.2%), and
      65.3% (+/-6.8%) of total cell OATP1B1 expression. Mean (+/-SD) plasma membrane
      expression of OATP1B3 in plated OATP1B3-expressing HEK293 cells, OATP2B1 in
      plated OATP2B1-expressing MDCKII cells, and sodium/taurocholate co-transporting
      polypeptide (NTCP) in plated NTCP-expressing CHO cells was 63.2% (+/-1.6%), 37.1%
      (+/-15.7%), and 71.7% (+/-1.2%), respectively. This method of quantifying
      transporter protein expression in the plasma membrane will be useful in the
      future to predict transporter-mediated drug disposition.

PMID- 28741222
TI  - Network of anatomical texts (NAnaTex), an open-source project for visualizing the
      interaction between anatomical terms.
AB  - Anatomy is the science and art of understanding the structure of the body and its
      components in relation to the functions of the whole-body system. Medicine is
      based on a deep understanding of anatomy, but quite a few introductory-level
      learners are overwhelmed by the sheer amount of anatomical terminology that must
      be understood, so they regard anatomy as a dull and dense subject. To help them
      learn anatomical terms in a more contextual way, we started a new open-source
      project, the Network of Anatomical Texts (NAnaTex), which visualizes
      relationships of body components by integrating text-based anatomical information
      using Cytoscape, a network visualization software platform. Here, we present a
      network of bones and muscles produced from literature descriptions. As this
      network is primarily text-based and does not require any programming knowledge,
      it is easy to implement new functions or provide extra information by making
      changes to the original text files. To facilitate collaborations, we deposited
      the source code files for the network into the GitHub repository (
      https://github.com/ryusukemomota/nanatex ) so that anybody can participate in the
      evolution of the network and use it for their own non-profit purposes. This
      project should help not only introductory-level learners but also professional
      medical practitioners, who could use it as a quick reference.

PMID- 28741223
TI  - Citrulline metabolism in plants.
AB  - Citrulline was chemically isolated more than 100 years ago and is ubiquitous in
      animals, plants, bacteria, and fungi. Most of the research on plant citrulline
      metabolism and transport has been carried out in Arabidopsis thaliana and the
      Cucurbitaceae family, particularly in watermelon which accumulates this non
      proteinogenic amino acid to very high levels. Industrially, citrulline is
      produced via specially optimized microbial strains; however, the amounts present
      in watermelon render it an economically viable source providing that other high
      value compounds can be co-extracted. In this review, we provide an overview of
      our current understanding of citrulline biosynthesis, transport, and catabolism
      in plants additionally pointing out significant gaps in our knowledge which need
      to be closed by future experimentation. This includes the identification of
      further potential enzymes of citrulline metabolism as well as obtaining a far
      better spatial resolution of both sub-cellular and long-distance partitioning of
      citrulline. We further discuss what is known concerning the biological function
      of citrulline in plants paying particular attention to the proposed roles in
      scavenging of excess NH4+ and as a compatible solute.

PMID- 28741224
TI  - Comparative analysis of Histone modifications and DNA methylation at OsBZ8 locus
      under salinity stress in IR64 and Nonabokra rice varieties.
AB  - Rice being an important cereal crop is highly sensitive to salinity stress
      causing growth retardation and loss in productivity. However, certain rice
      genotypes like Nonabokra and Pokkali show a high level of tolerance towards
      salinity stress compared to IR64 variety. This differential response of tolerant
      varieties towards salinity stress may be a cumulative effect of genetic and
      epigenetic factors. In this study, we have compared the salinity-induced changes
      in chromatin modifications at the OsBZ8 locus in salt-tolerant Nonabokra and salt
      sensitive IR64 rice varieties. Expression analysis indicates that the OsBZ8 gene
      is highly induced in Nonabokra plants even in the absence of salt stress, whereas
      in IR64, the expression significantly increases only during salt stress. Sequence
      analysis and nucleosomal arrangement within the region -2000 to +1000 of OsBZ8
      gene show no difference between the two rice varieties. However, there was a
      considerable difference in histone modifications and DNA methylation at the locus
      between these varieties. In Nonabokra, the upstream region was hyperacetylated at
      H3K9 and H3K27, and this acetylation did not change during salt stress. However,
      in IR64, histone acetylation was observed only during salt stress. Moreover, the
      upstream region of OsBZ8 gene has highly dynamic nucleosome arrangement in
      Nonabokra, compared to IR64. Furthermore, loss of DNA methylation was observed at
      OsBZ8 locus in Nonabokra control plants along with low H3K27me3 and high H3K4me3.
      Control IR64 plants show high DNA methylation and enriched H3K27me3. Collectively
      these results indicate a significant difference in chromatin modifications
      between the rice varieties that regulates differential expression of OsBZ8 gene
      during salt stress.

PMID- 28741225
TI  - Conversion of external ventricular drainage to ventriculo-peritoneal shunt: to
      change or not to change the proximal catheter?
AB  - PURPOSE: In this study, we investigate the occurrence rate of early shunt
      infection and malfunction in pediatric patients after converting an external
      ventricular drainage (EVD) to a ventriculo-peritoneal shunt (VPS) without
      replacing the ventricular catheter. METHODS: Data was retrospectively reviewed
      for 17 pediatric patients (11 male (64.7%), mean age 7.5 years, range 0.25-15
      years) who underwent 18 consecutive direct conversions of tunneled EVD to VPS
      without replacing the ventricular catheter between 2008 and 2017. In each case,
      the EVD was inserted in sterile fashion within the operating room and tunneled
      subcutaneously 5-7 cm away from the insertion site. Primary outcome measure was
      the occurrence of early (within 30 days) VPS infection or malfunction. The mean
      follow-up time was 56.8 months (+/-35.7 months). RESULTS: The mean period of EVD
      before VPS placement was 9.0 days (+/-3.6 days, range 2-18 days). Five patients
      had shunt infections/malfunctions. One patient (5.6%) had an early shunt
      infection after 30 days. One patient had a late shunt infection after 9 months.
      One patient had an early shunt malfunction after 9 days. Two patients (11.1%) had
      late shunt malfunctions after 6.5 months and 9 years. There were no other
      incidents of shunt-related complications or shunt-related mortality. CONCLUSION:
      In the pediatric population, the conversion of a tunneled EVD to a VPS without
      replacing the ventricular catheter can be safely done. Cranial entry is spared,
      while the rates of shunt infection and malfunction do not increase significantly.

PMID- 28741226
TI  - Costanzo Varolio (1543-1575), who named the "pons".

PMID- 28741227
TI  - Posterior fossa pilomyxoid astrocytoma with spontaneous hemorrhage in pediatric
      patients.
AB  - OBJECT: The tumor described in this report was unique because of its involvement
      with a posterior fossa spontaneous hemorrhage in a pediatric patient; such a case
      has never been previously described in cases of pilomyxoid astrocytomas and also
      rarely found in those of pilocytic astrocytomas. METHODS: This report studied a
      rare case of posterior fossa pilomyxoid astrocytoma (PMA) with critical and
      dangerous spontaneous hemorrhage. A 7-year-old girl appeared at the outpatient
      clinic with sudden headache and vomiting. RESULTS: The patient underwent gross
      total tumor resection via suboccipital Medline approach, and no evidence of
      residual or recurrent tumor was found on magnetic resonance images at two follow
      up examinations which were respectively conducted 1 and 5 months after resection.
      CONCLUSION: In this report, the authors reviewed the literature and discussed the
      clinical features and treatment of pilomyxoid astrocytoma. It is important to
      distinguish this tumor variant from the more indolent pilocytic astrocytoma.

PMID- 28741228
TI  - Craniocerebral birth injuries in term newborn infants: a retrospective series.
AB  - OBJECTIVE: In an attempt to further define the spectrum of cranial birth
      injuries, we analyzed 21 consecutive cranial birth injuries in term neonates
      presenting to the neurosurgical department of our institution over the period
      1994-2015. METHODS: We performed a retrospective chart review from the medical
      records of the University Hospitals of the KU Leuven, from 1994 to 2015. We
      included 21 infants of 36-week gestational age or older with a diagnosis of
      cranial birth injury. The types and locations of injuries, the presenting signs,
      symptoms and their timing, and the required treatment(s) were recorded. Various
      maternal and neonatal factors and the mode of delivery were recorded. We recorded
      the different modes of delivery rates at our institution in the year 2013 and the
      rates in the Flemish community between 1995 and 2013, in order to compare the
      mode of delivery rates in the study group with current practice at our
      institution and with general practice over the years in the Flemish community.
      RESULTS: The most common clinical presentations were swelling (43% of cases) and
      seizures (19% of cases). Average Apgar scores were 6.57 at 1 min and 8.43 at 5
      min; 48% of children had abnormally low Apgar scores at 1 min and 9.5% had
      abnormally low scores at 5 min. The most common intracranial lesion was skull
      fractures (33%). Operative treatment was required in 11 infants (52%). One infant
      died. Assisted mechanical delivery by either forceps and/or vacuum extraction
      occurred in 43% of infants. In comparison, in the year 2013, only 13.97% of
      deliveries at our institution were mechanically assisted. Over the period 1995
      2013, the highest mechanically assisted delivery rates in the Flemish community
      were 14.1% in 1996. CONCLUSION: Although our series is too small to make firm
      conclusions, it is remarkable that the rates of assisted mechanical deliveries in
      our series far exceeded the assisted mechanical delivery rates at our institution
      in the year 2013 and even the highest vacuum and forceps delivery rates in the
      Flemish community over the period 1995-2013.

PMID- 28741229
TI  - Inhaled Antimicrobials for Ventilator-Associated Pneumonia: Practical Aspects.
AB  - Positive experience with inhaled antibiotics in pulmonary infections of patients
      with cystic fibrosis has paved the way for their utilization in mechanically
      ventilated, critically ill patients with lower respiratory tract infections. A
      successful antibiotic delivery depends upon the size of the generated particle
      and the elimination of drug impaction in the large airways and the ventilator
      circuit. Generated droplet size is mainly affected by the type of the nebulizer
      employed. Currently, jet, ultrasonic, and vibrating mesh nebulizers are marketed;
      the latter can deliver optimal antibiotic particle size. Promising novel drug
      device combinations are able to release drug concentrations of 25- to 300-fold
      the minimum inhibitory concentration of the targeted pathogens into the pulmonary
      alveoli. The most important practical steps of nebulization include pre
      assessment and preparation of the patient (suctioning, sedation, possible
      bronchodilation, adjustment of necessary ventilator settings); adherence to the
      procedure (drug preparation, avoidance of unnecessary tubing connections,
      interruption of heated humidification, removal of heat-moisture exchanger);
      inspection of the procedure (check for residual in drug chamber, change of
      expiratory filter, return sedation, and ventilator settings to previous status);
      and surveillance of the patient for adverse events (close monitoring of the
      patient and particularly of peak airway pressure and bronchoconstriction).
      Practical aspects of nebulization are very important to ensure optimal drug
      delivery and safe procedure for the patient. Therefore, the development of an
      operational checklist is a priority for every department adopting this modality.

PMID- 28741230
TI  - New Therapeutic Strategies for Lewy Body Dementias.
AB  - This article reviews current treatment strategies and recent advances for the
      Lewy body dementias (LBDs). Current available symptom treatment strategies are
      based on monoaminergic, cholinergic and glutaminergic neurotransmitter systems.
      Relatively robust evidence exists for cholinesterase inhibitors for cognitive
      impairment in LBD and in Parkinson's disease for antidepressants, clozapine and
      recently pimavanserin for psychosis. interpidine (RVT 101) and nelotanserin are
      currently under investigation. Non-pharmacological interventions, such as
      cognitive stimulation, physical exercises and neuromodulation strategies, may be
      useful in Parkinson's disease but have not yet been tested in dementias. Disease
      modifying approaches are aimed at preventing, slowing or ameliorating the
      production, aggregation and deposition of pathological proteins, including
      immunotherapy targeting alpha-synuclein and an ongoing trial using ambroxol which
      increases glucocerebrosidase activity to lower the levels of the protein alpha
      synuclein. Other disease-modifying clinical trials are using agents to augment
      insulin signalling, stem cell therapy, reducing amyloid pathology and gene
      therapy.

PMID- 28741231
TI  - Large Cell Transformation of Oral Mycosis Fungoides.
AB  - Mycosis fungoides (MF) accounts for approximately 50% of all primary cutaneous
      lymphomas. MF occurrence in the oral cavity is extremely rare with approximately
      45 cases reported to date. We present a case of a 68 year-old man with a raised
      nodular lesion of the ventral tongue with clinical impression of irritational
      fibroma. Histopathologic and immunohistochemical (IHC) examination revealed a
      phenotype consistent with MF with large cell transformation in the context of
      Sezary syndrome. The histological diagnosis of oral MF requires a high index of
      suspicion and IHC panel to rule out large cell transformation. To our knowledge,
      only four cases of large cell transformation of oral MF have been reported in the
      English literature. The clinical and histopathologic features of a rare case of
      intra-oral MF with large cell transformation are exemplified in this article.

PMID- 28741232
TI  - Serum and aqueous humor concentrations of interleukin-27 in diabetic retinopathy
      patients.
AB  - PURPOSE: Interleukin (IL)-27 has been reported to possess anti- and
      proinflammatory properties in several immune related-disorders, but its role in
      diabetic retinopathy is still elusive. Here, we aimed to (i) evaluate IL-27
      concentrations in serum and aqueous humor of diabetic patients with or without
      retinopathy and (ii) test whether IL-27 is correlated with some risk factors of
      diabetic retinopathy. METHODS: The study comprised 60 diabetic patients with and
      without retinopathy along with 20 healthy controls. Serum and aqueous humor
      concentrations of IL-27 were assessed by ELISA. RESULTS: The mean of IL-27
      concentration in aqueous humor in patients with diabetic retinopathy (6.7 +/- 2.7
      ng/L) was significantly elevated in comparison with either diabetic patients
      without retinopathy (4.6 +/- 0.5 ng/L) or healthy control group (4.1 +/- 0.8
      ng/L). Besides, IL-27 concentration in aqueous humor was positively correlated
      with serum glucose, lipid profile and glycated hemoglobin (HbA1c). CONCLUSIONS:
      Based on this study, IL-27 is implicated in the pathogenesis of diabetic
      retinopathy and positively correlates with the disorder progression.

PMID- 28741233
TI  - How to Identify High-Risk APS Patients: Clinical Utility and Predictive Values of
      Validated Scores.
AB  - PURPOSE OF REVIEW: Antiphospholipid syndrome (APS) is a clinical disorder
      characterised by thrombosis and/or pregnancy morbidity in the persistence of
      antiphospholipid (aPL) antibodies that are pathogenic and have pro-coagulant
      activities. Thrombosis in APS tends to recur and require prophylaxis; however,
      the stereotypical treatment for APS patients is inadequate and stratification of
      the thrombotic risks is important as aPL are prevalently observed in various
      diseases or elderly population. RECENT FINDINGS: It is previously known that the
      multiple positive aPL or high titre aPL correlate to thrombotic events. To
      progress the stratification of thrombotic risks in APS patients and to
      quantitatively analyse those risks, antiphospholipid score (aPL-S) and the Global
      Anti-phospholipid Syndrome Score (GAPSS) were defined. These scores were raised
      from the large patient cohort data and either aPL profile classified in detail
      (aPL-S) or simplified aPL profile with classical thrombotic risk factors (GAPSS)
      was put into a scoring system. Both the aPL-S and GAPSS have shown a degree of
      accuracy in identifying high-risk APS patients, especially those at a high risk
      of thrombosis. However, there are several areas requiring improvement, or at
      least that clinicians should be aware of, before these instruments are applied in
      clinical practice. One such issue is standardisation of the aPL tests, including
      general testing of phosphatidylserine-dependent antiprothrombin antibodies
      (aPS/PT). Additionally, clinicians may need to be aware of the patient's medical
      history, particularly with respect to the incidence of SLE, which influences the
      cutoff value for identifying high-risk patients.

PMID- 28741234
TI  - Direct Oral Anticoagulants Use in Antiphospholipid Syndrome: Are These Drugs an
      Effective and Safe Alternative to Warfarin? A Systematic Review of the
      Literature: Response to Comment.

PMID- 28741235
TI  - Making Patient Engagement a Reality.
AB  - Patients are increasingly recognised as the true customers of healthcare. By
      providing insights and perspectives, patients can help the wider healthcare
      community better understand their needs and ultimately enhance the value of
      healthcare solutions being developed. In the development of new medicines, for
      example, meaningful patient engagement can enable the pharmaceutical industry,
      healthcare providers and other stakeholders to achieve more meaningful health
      outcomes. While both the pharmaceutical industry and regulators have achieved
      some progress in incorporating patient perspectives into their activities, the
      lack of standardised best practices and metrics has made it challenging to
      achieve consistency and measure success in patient engagement. Practical guidance
      for patient engagement can facilitate better interactions between patients or
      patient groups and other collaborators, e.g. industry, regulators and other
      healthcare stakeholders. Accordingly, UCB has developed an internal model for
      Patient Group Engagement incorporating four key principles, based on shared
      ambition, transparency, accountability and respect, essential for effective
      collaborations.

PMID- 28741236
TI  - Awareness about celiac disease amongst physicians.

PMID- 28741237
TI  - Cytotoxic T lymphocytes and CD4 epitope mutations in the pre-core/core region of
      hepatitis B virus in chronic hepatitis B carriers in Northeast Iran.
AB  - BACKGROUNDS: Hepatitis B virus (HBV) is vulnerable to many various mutations.
      Those within epitopes recognized by sensitized T cells may influence the re
      emergence of the virus. This study was designed to investigate the mutation in
      immune epitope regions of HBV pre-core/core among chronic HBV patients of
      Golestan province, Northeast Iran. METHODS: In 120 chronic HBV carriers, HBV DNA
      was extracted from blood plasma samples and PCR was done using specific primers.
      Direct sequencing and alignment of the pre-core/core region were applied using
      reference sequence from Gene Bank database (Accession Number AB033559). RESULTS:
      The study showed 27 inferred amino acid substitutions, 9 of which (33.3%) were in
      CD4 and 2 (7.4%) in cytotoxic T lymphocytes' (CTL) epitopes and 16 other
      mutations (59.2%) were observed in other regions. CONCLUSIONS: CTL escape
      mutations were not commonly observed in pre-core/core sequences of chronic HBV
      carriers in the locale of study. It can be concluded that most of the inferred
      amino acid substitutions occur in different immune epitopes other than CTL and
      CD4.

PMID- 28741238
TI  - A Randomized Comparison Between Staple-Line Oversewing Versus No Reinforcement
      During Laparoscopic Vertical Sleeve Gastrectomy.
AB  - BACKGROUND: Varieties of intraoperative methods such as oversewing of staple
      lines or other reinforcement products are used for preventing the laparoscopic
      vertical sleeve gastrectomy (LSG) complications. The aim of this study is to
      evaluate the complication rates of the gastric stapling alone versus stapling
      with oversewing invagination of the staple line in the LSG. METHODS: This is a
      single-center randomized study, Patients were randomized to two groups, 200
      patients underwent LSG without reinforcement of the staple line and 200 patients
      underwent LSG with oversewing of the staple line. All patients were followed up
      for 1 year. The data collected prospectively for statistical analysis included
      demographics, BMI, preoperative comorbidities, operative time, complications, and
      hospital stay. RESULTS: The overall mean operative age was 33.7 +/- 9.4 years and
      mean BMI was 42.4 +/- 4.3 kg/m2. Patient baseline characteristics (age, gender,
      weight, and BMI) and comorbidities were generally a nonsignificant different
      between the treatment arms. Surgical time was shorter in patients of the
      nonreinforced group (44.3 +/- vs 51.3 +/- 4.3 min; p < 0.01) with lower %EWL (73
      +/- 13.8 vs 80.7 +/- 13.6%, p < 0.01). One patient in the nonreinforced group was
      complicated by gastric leak. The staple-line bleeding rate was significantly
      lower in patients underwent oversewing of the staple line during LSG (p < 0.05).
      CONCLUSION: Oversewing of the staple line during LSG is a nonexpansive and easy
      method to decrease the incidence and severity of the postoperative bleeding.
      However, it is time-consuming and should be performed by experienced surgeons to
      avoid the complications which may occur secondary to the seroserotomy suturing.

PMID- 28741239
TI  - Type 2 Diabetes Mellitus and Simple Glucose Metabolism Parameters may Reliably
      Predict Nonalcoholic Fatty Liver Disease Features.
AB  - OBJECTIVE: This study aims to investigate the correlation between features of
      NAFLD among individuals with morbid obesity and the surrogate IR markers
      homeostasis model assessment (HOMA), product of triglycerides and glucose (TyG),
      and triglyceride-to-high-density-lipoprotein ratio (TG/HDL-c). METHODS: A cross
      sectional study, which enrolled 89 individuals who consecutively underwent
      bariatric surgery from February through December 2015, was conducted. NAFLD was
      assessed through histological examination of liver biopsies and correlated with
      the values of HOMA, TyG, and TG/HDL-c and their respective cutoff points for
      insulin resistance (IR). RESULTS: xThe prevalence of liver steatosis was 68.5%;
      the affected individuals presented significantly higher fasting glucose levels (p
      < 0.01) and hemoglobin A1c (p < 0.01), and a significantly higher prevalence of
      type 2 diabetes mellitus (T2DM) (p < 0.001). Fibrosis occurred in 66.3% of the
      individuals and was significantly associated with higher levels of HbA1c (p <
      0.05) and a higher prevalence of T2DM (p < 0.05). Steatohepatitis was present in
      64% of the individuals and was significantly associated with older age (p <
      0.05), higher levels of fasting glucose (p < 0.05), and a higher prevalence of
      T2DM (p < 0.001). After Bonferroni's adjustment, T2DM was significantly
      correlated with fibrosis (p < 0.01) and steatohepatitis (p < 0.001) and older age
      was significantly correlated with fibrosis (p < 0.05). T2DM was the only variable
      independently associated with fibrosis and steatohepatitis (p < 0.05 in both
      cases). CONCLUSION: T2DM was a significant predictor of NAFLD features among
      individuals undergoing bariatric surgery; higher Hb A1c was correlated with
      fibrosis. T2DM was independently associated with fibrosis and steatohepatitis.
      HOMA, TyG, and TG/HDL-c ratio did not present significant associations with
      NAFLD.

PMID- 28741240
TI  - The Underestimated Effect of Perioperative Exercise Interventions in Bariatric
      Surgery: Increasing Need for Large Impact Studies.

PMID- 28741241
TI  - Addition to the Special Issue on the CTP network consisting of reviews and
      original papers emerging from the CTPIOD meeting (Contribution To Progress in
      Obesity and Diabetes Research) 2016.

PMID- 28741242
TI  - The weakening effect of soluble epoxide hydrolase inhibitor AUDA on febrile
      response to lipopolysaccharide and turpentine in rat.
AB  - A still growing body of evidence suggests the importance of epoxyeicosatrienoic
      acids (EETs) in the regulation of inflammatory response; therefore, drugs that
      stabilize their levels by targeting the soluble epoxide hydrolase (sEH), an
      enzyme responsible for their metabolism, are currently under investigation. The
      effect of sEH inhibitors on molecular components of fever mechanism, i.e., on
      synthesis of pro-inflammatory cytokines or prostaglandins, has been repeatedly
      proven; however, the hypothesis that sEH inhibitors affect febrile response has
      never been tested. The aim of this study was to examine if sEH inhibition affects
      core body temperature (Tb) as well as Tb changes during febrile response to
      infectious (lipopolysaccharide; LPS) or non-infectious (turpentine; TRP) stimuli.
      Male Wistar rats were implanted intra-abdominally with miniature biotelemeters to
      monitor Tb. A potent sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid
      (AUDA) was suspended in olive oil and administrated into animals in the
      intraperitoneal (i.p.) dose of 15 mg/kg, which, as we showed, has no significant
      influence on normal Tb. We have found that AUDA injected 3 h after LPS (50 MUg/kg
      i.p.) significantly weakened febrile rise of Tb. Moreover, injection of sEH
      inhibitor 7 h after turpentine (administrated subcutaneously in a dose of 100
      MUL/rat) markedly reduced the peak period of aseptic fever. Obtained results
      provide first experimental evidence that sEH inhibitors possess anti-pyretic
      properties. Therefore, medicines targeting sEH enzymatic activity should be
      considered as a complement to the arsenal of topical medications used to treat
      fever especially in clinical situations when non-steroidal anti-inflammatory
      drugs are ineffective.

PMID- 28741243
TI  - The Pharmacogenomic and Metabolomic Predictors of ACE Inhibitor and Angiotensin
      II Receptor Blocker Effectiveness and Safety.
AB  - Hypertension (HTN) is the most common chronic disease in the USA. Hypertensive
      patients frequently require repeat primary care visits to find an effective drug
      or drug combination to control their disease. Currently, patients are prescribed
      drugs for HTN based on race, age, and comorbidities and although the current
      guidelines are reasonable starting points for prescribing, 50% of hypertensive
      patients still fail to achieve target blood pressures. Despite numerous
      strategies to improve compliance, drug effectiveness, and optimization of initial
      drug choice, effectiveness has remained largely unchanged over the past two
      decades. Therefore, it is important to pursue alternative strategies to more
      effectively treat patients and to decrease medical costs. Additional precision
      medicine work is needed to identify factors associated with effectiveness of
      commonly used antihypertensive medications. The objective of this manuscript is
      to present a comprehensive review of the pharmacogenomic and metabolomic factors
      associated with ACEI and ARB effectiveness and safety.

PMID- 28741244
TI  - Efficacy and Safety of Alternate-Day Versus Daily Dosing of Statins: a Systematic
      Review and Meta-Analysis.
AB  - PURPOSE: We conducted a meta-analysis of randomized controlled trials (RCTs) and
      quasi-RCTs to synthesize evidence about the efficacy and safety of alternate-day
      vs daily dosing of statins. METHODS: We searched selected databases through
      January 2, 2017 to identify relevant RCTs and quasi-RCTs. The primary outcome was
      change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC),
      and triglycerides (TG), while secondary outcomes included adverse events and
      adherence. RESULTS: Twelve RCTs and 1 quasi-RCT (n = 1023 patients) were included
      in the analysis. Pooled analysis revealed no statistically significant difference
      between alternate-day and daily regimens of atorvastatin and rosuvastatin in
      terms of change in LDL-C (mean difference [MD] 6.79 mg/dL, 95% confidence
      interval [CI] -1.59, 15.17, p = 0.11, and 10.51 mg/dL, 95%CI -0.23, 21.26, p =
      0.06, respectively) and TG (p > 0.05). Daily regimens of atorvastatin and
      rosuvastatin were superior to alternate-day regimes in term of change in TC (MD
      12.45 mg/L, 95%CI 8.14, 16.76, p < 0.00001, and 15.80 mg/dL, 95%CI 5.66, 25.95, p
      = 0.002, respectively). For all outcomes, there was no statistically significant
      difference between alternate-day and daily regimens for both fluvastatin and
      pravastatin (p > 0.05). Both regimens of statins were generally well tolerated
      with good adherence. CONCLUSIONS: Alternate-day dosing of individual statins
      (especially atorvastatin and rosuvastatin) is as efficacious as daily dosing on
      LDL-C and TG.

PMID- 28741245
TI  - The last frontier: transcatheter devices for percutaneous or minimally invasive
      treatment of chronic heart failure.
AB  - Heart failure has a high prevalence in the general population. Morbidity and
      mortality of heart failure patients remain high, despite improvements in drug
      therapy, implantable cardioverter-defibrillators and cardiac resynchronisation
      therapy. New transcatheter implantable devices have been developed to improve the
      treatment of heart failure. There has been a rapid development of minimally
      invasive or transcatheter devices used in the treatment of heart failure
      associated with aortic and mitral valve disease and these devices are being
      incorporated into routine clinical practice at a fast rate. Several other new
      transcatheter structural heart interventions for chronic heart failure aimed at a
      variety of pathophysiologic approaches are currently being developed. In this
      review, we focus on devices used in the treatment of chronic heart failure by
      means of left ventricular remodelling, left atrial pressure reduction, tricuspid
      regurgitation reduction and neuromodulation. The clinical evaluations of these
      devices are early-stage evaluations of initial feasibility and safety studies and
      additional clinical evidence needs to be gathered in appropriately designed
      clinical trials.

PMID- 28741246
TI  - Successful resection after neoadjuvant chemotherapy for esophageal cancer with
      posterior thoracic paraaortic lymph node metastasis: a case report and literature
      review.
AB  - Metastasis to the posterior thoracic paraaortic lymph nodes rarely occurs in
      esophageal cancer, and a treatment strategy has not been established. We treated
      two cases of esophageal cancer with this type of metastasis; in both cases, we
      successfully performed surgical resection after neoadjuvant chemotherapy. In case
      1, the patient received neoadjuvant chemotherapy, which consisted of docetaxel,
      cisplatin and 5-fluorouracil, and then underwent dissection of the posterior
      thoracic paraaortic lymph nodes. The left thoracic approach was used together
      with subtotal esophagectomy via a right thoracotomy. In case 2, the patient also
      received neoadjuvant chemotherapy and underwent dissection of the posterior
      thoracic paraaortic lymph nodes. The left thoracoscopic approach was used
      together with a subtotal esophagectomy and a right upper and middle pulmonary
      lobectomy (due to lung cancer) with a right thoracotomy. After 42 and 12 months'
      post-surgery, respectively, the patients were doing well without any evidence of
      recurrence.

PMID- 28741247
TI  - Contaminants of emerging concern: a review of new approach in AOP technologies.
AB  - The presence of contaminants of emerging concern (CECs) such as pharmaceuticals
      and personal care products (PPCPs), endocrine-disrupting compounds (EDCs), flame
      retardants (FRs), pesticides, and artificial sweeteners (ASWs) in the aquatic
      environments remains a major challenge to the environment and human health. In
      this review, the classification and occurrence of emerging contaminants in
      aquatic environments were discussed in detail. It is well documented that CECs
      are susceptible to poor removal during the conventional wastewater treatment
      plants, which introduce them back to the environment ranging from nanogram per
      liter (e.g., carbamazepine) up to milligram per liter (e.g., acesulfame)
      concentration level. Meanwhile, a deep insight into the application of advanced
      oxidation processes (AOPs) on mitigation of the CECs from aquatic environment was
      presented. In this regard, the utilization of various treatment technologies
      based on AOPs including ozonation, Fenton processes, sonochemical, and TiO2
      heterogeneous photocatalysis was reviewed. Additionally, some innovations (e.g.,
      visible light heterogeneous photocatalysis, electro-Fenton) concerning the AOPs
      and the combined utilization of AOPs (e.g., sono-Fenton) were documented.

PMID- 28741248
TI  - Lessons Learned from Arsenic Mitigation among Private Well Households.
AB  - PURPOSE OF REVIEW: Many thousands of research papers have been published on the
      occurrence, health effects, and mitigation of arsenic in drinking water sourced
      from groundwater around the world. Here, an attempt is made to summarize this
      large body of knowledge into a small number of lessons. RECENT FINDINGS: This is
      an opinion paper reflecting on why we are far from the goal of eliminating this
      silent and widespread poison to protect the health of many millions. The lessons
      are drawn from research in countries representing a range of economic development
      and cultural contexts. The replacement of household wells with centralized water
      supplies has reduced population level exposure to moderate (50-100 MUg/L) and
      high (>100 MUg/L) levels of arsenic in drinking water in some countries as they
      become wealthier. However, there remains a very large rural population in all
      countries where the exposure to low levels (10-50 MUg/L) of arsenic continues due
      to its dispersed occurrence in the environment and frequent reliance on private
      well. A set of natural (geological and biological), socioeconomic, and behavioral
      barriers to progress are summarized as lessons. They range from challenges in
      identifying the exposed households due to spatially heterogeneous arsenic
      distribution in groundwater, difficulties in quantifying the exposure let alone
      reducing the exposure, failures in maintaining compliance to arsenic drinking
      water standards, to misplaced risk perceptions and environmental justice issues.
      Environmental health professionals have an ethical obligation to help As
      mitigation among private well water households, along with physicians,
      hydrogeologists, water treatment specialists, community organizations, and
      government.

PMID- 28741249
TI  - Ambroise Pare (1510-1590): on the diagnosis and treatment of shoulder
      dislocations.
AB  - AIM OF STUDY: This article aims to summarize the treatment methods for shoulder
      dislocations supported by Ambroise Pare, and his clinical and academic
      contribution to this subject. INTRODUCTION: Ambroise Pare (1510-1590) was one of
      the most prominent surgeons of his time, and one of the most significant
      innovators of the Renaissance in the fields of military operation, bandages,
      wound healing, bloodletting, close blood vessels techniques and cesarean section.
      For many, he is considered "the Father of Modern Surgery". METHODS: In our search
      we went through the literature in Pubmed and Google Scholar as well as the works
      of Hippocrates and Galen and several other ancient and medieval authors. RESULTS:
      His work on shoulder injuries and dislocations is outstanding. In this work, he
      uses the classifications of Hippocrates (460-377 BC) and Galen (130-201 BC). He
      also uses the reduction techniques, ointments, bandages, cooling creams and
      treatment options described by the ancient medical authors. DISCUSSION: Pare is
      heavily based on the work of previous authors on shoulder dislocations. He uses
      the work of Hippocrates and Galen as well as the additions made in the Cannon of
      Medicne of Avicenna. CONCLUSION: Ambroise Pare in his excellent work on shoulder
      dislocations uses the classifications of Hippocrates and Galen and the reduction
      techniques, cooling ointments, bandages and post-reduction management options as
      previously described by Hippocrates himself.

PMID- 28741250
TI  - Effects of deoxynivalenol (DON) and its microbial biotransformation product
      deepoxy-deoxynivalenol (DOM-1) on a trout, pig, mouse, and human cell line.
AB  - Deoxynivalenol (DON), a trichothecene produced by various Fusarium species, is
      one of the most prevalent food- and feed-associated mycotoxins. The effects of
      DON and deepoxy-deoxynivalenol (DOM-1) were assessed in five different cell lines
      from different tissues and species starting from the first line of defense, the
      trout gill (RTgill-W1) and pig intestinal cells (IPEC-1 and IPEC-J2) over immune
      cells, as second line of defense (mouse macrophages RAW 264.7) to human liver
      cells (HepG2). Viability was assessed with a WST-1 assay, except for RTgill-W1,
      where a neutral red (NR) and sulforhodamine B (SRB) assay was performed.
      Additionally, more sensitive parameters, such as interleukin-, nitric oxide (NO)
      , and albumin-release were determined. Viability was affected by DON at
      concentrations starting at 10 MUmol/L (RTgill-W1), 0.9 MUmol/L (IPEC-1), 3.5
      MUmol/L (IPEC-J2), and 0.9 MUmol/L (HepG2), whereas DOM-1 did not have such an
      effect. Additionally, NO was decreased (0.84 MUmol/L DON), whereas interleukin
      (IL)-6 was increased (0.42 MUmol/L DON) in lipopolysaccharide (LPS)-stimulated
      DON-, but not DOM-1-treated RAW cells. Tumor necrosis factor (TNF)-alpha release,
      however, was not affected. Interestingly, albumin secretion of HepG2 cells was
      decreased by both DON and DOM-1 but at a much higher concentration for DOM-1 (228
      versus 0.9 MUmol/L for DON). 98.9% of DOM-1 was retrieved by liquid
      chromatography tandem mass spectrometry at the end of the experiment, proving its
      stability. In this study, IL-6 was the most sensitive parameter, followed by NO
      and albumin release and viability for HepG2 and IPEC-1.

PMID- 28741251
TI  - The role of top-down suppression in mitigating the disruptive effects of task
      irrelevant feature changes in visual working memory.
AB  - Studies of change detection have shown that changing the task-irrelevant features
      of remembered objects impairs change detection for task-relevant features, a
      phenomenon known as the irrelevant change effect. Although this effect is
      pronounced at short study-test intervals, it is eliminated at longer delays. This
      has prompted the proposal that although all features of attended objects are
      initially stored together in visual working memory (VWM), top-down control can be
      used to suppress task-irrelevant features over time. The present study reports
      the results of three experiments aimed at testing the top-down suppression
      hypothesis. Experiments 1 and 2 tested whether the magnitude or time course of
      the irrelevant change effect was affected by the concurrent performance of a
      demanding executive load task (counting backwards by threes). Contrary to the top
      down suppression view, the decreased availability of executive resources did not
      prolong the duration of the irrelevant change effect in either experiment, as
      would be expected if these resources were necessary to actively suppress task
      irrelevant features. Experiment 3 showed that a visual pattern mask eliminates
      the irrelevant change effect and suggests that the source of the effect may lie
      in the use a high-resolution, sensory memory representation to match the memory
      and test displays when no task-irrelevant feature changes are present. These
      results suggest that the dissipation of the irrelevant change effect over time
      likely does not depend on the use of top-down control and raises questions about
      what can be inferred about the nature of storage in VWM from studies of this
      effect.

PMID- 28741252
TI  - Serial recall of colors: Two models of memory for serial order applied to
      continuous visual stimuli.
AB  - This study investigated the effects of serial position and temporal
      distinctiveness on serial recall of simple visual stimuli. Participants observed
      lists of five colors presented at varying, unpredictably ordered interitem
      intervals, and their task was to reproduce the colors in their order of
      presentation by selecting colors on a continuous-response scale. To control for
      the possibility of verbal labeling, articulatory suppression was required in one
      of two experimental sessions. The predictions were derived through simulation
      from two computational models of serial recall: SIMPLE represents the class of
      temporal-distinctiveness models, whereas SOB-CS represents event-based models.
      According to temporal-distinctiveness models, items that are temporally isolated
      within a list are recalled more accurately than items that are temporally
      crowded. In contrast, event-based models assume that the time intervals between
      items do not affect recall performance per se, although free time following an
      item can improve memory for that item because of extended time for the encoding.
      The experimental and the simulated data were fit to an interference measurement
      model to measure the tendency to confuse items with other items nearby on the
      list-the locality constraint-in people as well as in the models. The continuous
      reproduction performance showed a pronounced primacy effect with no recency, as
      well as some evidence for transpositions obeying the locality constraint. Though
      not entirely conclusive, this evidence favors event-based models over a role for
      temporal distinctiveness. There was also a strong detrimental effect of
      articulatory suppression, suggesting that verbal codes can be used to support
      serial-order memory of simple visual stimuli.

PMID- 28741253
TI  - Dissociations of the number and precision of visual short-term memory
      representations in change detection.
AB  - The present study dissociated the number (i.e., quantity) and precision (i.e.,
      quality) of visual short-term memory (STM) representations in change detection
      using receiver operating characteristic (ROC) and experimental manipulations.
      Across three experiments, participants performed both recognition and recall
      tests of visual STM using the change-detection task and the continuous color
      wheel recall task, respectively. Experiment 1 demonstrated that the estimates of
      the number and precision of visual STM representations based on the ROC model of
      change-detection performance were robustly correlated with the corresponding
      estimates based on the mixture model of continuous-recall performance.
      Experiments 2 and 3 showed that the experimental manipulation of mnemonic
      precision using white-noise masking and the experimental manipulation of the
      number of encoded STM representations using consolidation masking produced
      selective effects on the corresponding measures of mnemonic precision and the
      number of encoded STM representations, respectively, in both change-detection and
      continuous-recall tasks. Altogether, using the individual-differences (Experiment
      1) and experimental dissociation (Experiment 2 and 3) approaches, the present
      study demonstrated the some-or-none nature of visual STM representations across
      recall and recognition.

PMID- 28741254
TI  - Performance bias: Why judgments of learning are not affected by learning.
AB  - Past research has shown a performance bias: People expect their future
      performance level on a task to match their current performance level, even when
      there are good reasons to expect future performance to differ from current
      performance. One explanation of this bias is that judgments are controlled by
      what learners can observe, and while current performance is usually observable,
      changes in performance (i.e., learning or forgetting) are not. This explanation
      makes a prediction that we tested here: If learning becomes observable, it should
      begin to affect judgments. In three experiments, after practicing a skill,
      participants estimated how they performed in the past and how they expected to
      perform in the future. In Experiments 1 and 2, participants knew they had been
      improving, as shown by their responses, yet they did not predict that they would
      improve in the future. This finding was particularly striking because (a) they
      did improve in the future and (b) as Experiment 3 showed, they did hold the
      conscious belief that past improvement predicted future improvement. In short,
      when learning and performance are both observable, judgments of learning seem to
      be guided by performance and not learning.

PMID- 28741255
TI  - Genetics of Schizophrenia: Ready to Translate?
AB  - PURPOSE OF REVIEW: This is an era where we have significantly advanced the
      understanding of the genetic architecture of schizophrenia. In this review, we
      consider how this knowledge may translate into advances that will improve patient
      care. RECENT FINDINGS: Large-scale genome-wide association studies (GWAS) have
      identified more than a hundred loci each making a small contribution to illness
      risk. Meta-analysis of copy number variants (CNVs) in the Psychiatric Genomics
      Consortium (PGC) dataset has confirmed that some variants have a moderate or
      large impact on risk, although these are rare in the population. Genome
      sequencing advances allow a much more comprehensive evaluation of genomic
      variation. We describe the key findings from whole exome studies to date. These
      studies are happening against a backdrop of growing understanding of the
      regulation and expression of genes and better functional tools to investigate
      molecular mechanisms in model systems. We provide an overview of how recent
      approaches in schizophrenia genetics are converging and consider how they could
      impact on diagnostics, the development of personalized medicine, and drug
      discovery.

PMID- 28741256
TI  - Measuring Work Ability with Its Antecedents: Evaluation of the Work Ability
      Survey.
AB  - Purpose The revised version of the Work Ability Survey (WAS-R) assesses work
      ability on several sub-scales at the intersection of personal and organizational
      capacity, thus adding to the measurement of work ability by integrating the
      holistic model. It, therefore, improves on two features of the current standard
      measurement tool of work ability, the Work Ability Index (WAI): (1) a ceiling
      effect and (2) limited detail due to a focus on physical health and personal
      capacity. Method In two samples (n 1 = 1093, n 2 = 359), psychometric properties
      and the structure of the WAS-R were analyzed. To evaluate construct validity,
      inter-correlations of the WAS-R and WAI, sickness absence, expected and desired
      retirement age, and post-retirement work intention were calculated. Results The
      WAS-R was found to be distributed closer to normality than the WAI. The
      structural analyses yielded acceptable results for the hypothesized model. The
      WAS-R was adequately correlated with the WAI, negatively with sickness absence,
      and positively with desired retirement age. Conclusions The WAS-R extends the
      measurement of work ability, reflecting organizations' work demands. Its broad
      sub-scales lead to high acceptance of the results within the participating
      companies. In particular, the organizational capacity scales can be used to guide
      interventions aiming at organizational characteristics to improve work ability.

PMID- 28741257
TI  - The comorbidity burden of patients with cluster headache: a population-based
      study.
AB  - BACKGROUND: Evidence is limited regarding the comorbidity burden of patients with
      cluster headache (CH). We aimed to characterize comorbid conditions in a cohort
      of CH patients diagnosed by headache experts, using electronic health record
      information from the Partners Research Patient Data Registry (RPDR). METHODS: We
      identified and reviewed the charts of unique patients diagnosed by headache
      specialists over an 11-year period, and a set of matched controls. Patients were
      categorized as having Definite, Unconfirmed or no CH. We calculated the
      prevalence of and tested for statistically significant differences of selected
      comorbid conditions in these populations. RESULTS: An RPDR query identified 170
      patients with a free text or ICD diagnosis of cluster headache. 15 records
      belonging to Partners employees were excluded. 75 patients met diagnostic
      criteria for CH (Definite CH). 22 had headaches with some features of CH but the
      diagnosis was uncertain (Unconfirmed CH). In 58 the diagnosis was determined to
      be inaccurate due to data entry errors. Patients with Definite CH had an average
      age of 43.4 years; 80% were male. The average time from CH onset to diagnosis was
      12.7 years (range 1-51). The average number of yearly emergency department and
      outpatient visits for the group of Definite CH patients was 4.5 and 25.4,
      respectively, compared with 1.1 and 6.9 in controls. Of the 55 examined
      conditions, four were statistically significantly less common in patients with
      definite CH compared with controls (diabetes, musculoskeletal/orthopaedic
      problems, "other gastrointestinal diagnoses" and skin conditions) and four were
      statistically significantly more common (smoking, depression, dental disorders
      and deviated septum). CONCLUSIONS: In this large population-based study, we
      identified a surprisingly small number of patients who met strict diagnostic
      criteria for CH. In these patients, however, we identified a distinct pattern of
      selected comorbidities. The pattern is somewhat but not entirely consistent with
      that of the "classic" CH patient depicted in the medical literature. CH patients
      are frequently diagnosed with sinus or dental problems. Many experience
      substantial delay in receiving a diagnosis. These things may in part explain the
      high frequency of medical visits in this population. It is difficult to
      distinguish conditions that are genuinely comorbid with CH from those that
      reflect misdiagnoses or medical scrutiny of patients in frequent contact with the
      healthcare system.

PMID- 28741258
TI  - Polymorphisms in miRNA genes and their involvement in autoimmune diseases
      susceptibility.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate
      the expression of multiple protein-encoding genes at the post-transcriptional
      level. MicroRNAs are involved in different pathways, such as cellular
      proliferation and differentiation, signal transduction and inflammation, and play
      crucial roles in the development of several diseases, such as cancer, diabetes,
      and cardiovascular diseases. They have recently been recognized to play a role
      also in the pathogenesis of autoimmune diseases. Although the majority of studies
      are focused on miRNA expression profiles investigation, a growing number of
      studies have been investigating the role of polymorphisms in miRNA genes in the
      autoimmune diseases development. Indeed, polymorphisms affecting the miRNA genes
      can modify the set of targets they regulate or the maturation efficiency. This
      review is aimed to give an overview about the available studies that have
      investigated the association of miRNA gene polymorphisms with the susceptibility
      to various autoimmune diseases and to their clinical phenotypes.

PMID- 28741259
TI  - Adoptive transfer of autoimmune splenic dendritic cells to lupus-prone mice
      triggers a B lymphocyte humoral response.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
      increased autoantibody production that leads to multiple tissue injuries.
      Dendritic cells (DCs) are important orchestrators of immune responses and key
      components in fine-tuning the balance between tolerance and immunity. However,
      their role in autoimmune disorders such as SLE remains uncertain. We analyzed the
      contribution of DCs in triggering SLE by adoptively transferring splenic DCs from
      aged autoimmune [NZB*NZW]F1 (BWF1) mice to young healthy BWF1 mice. We observed
      that the transfer of DCs from autoimmune mice to pre-autoimmune mice induced high
      autoantibody titers in the serum of recipient mice. Moreover, autoimmune DCs from
      aged BWF1 mice were crucial for the expansion and differentiation of plasmablasts
      and CD5+ B cells or B1-like cells in the peripheral blood, and spleen of
      recipient BWF1 mice, a phenomenon that is observed in autoimmune BWF1 mice. On
      the other hand, DCs from aged BWF1 mice participated in the expansion and
      differentiation of DCs and IFN-gamma-producing T cells. These results reveal that
      DCs from autoimmune BWF1 mice exhibit functional and phenotypic characteristics
      that allow them to trigger B cell hyperactivation, as well as DC and T cell
      expansion and differentiation, thereby promoting an exacerbated humoral response
      in lupus-prone mice.

PMID- 28741260
TI  - The Androgen Receptor Supports Tumor Progression After the Loss of Ovarian
      Function in a Preclinical Model of Obesity and Breast Cancer.
AB  - The androgen receptor (AR) has context-dependent roles in breast cancer growth
      and progression. Overall, high tumor AR levels predict a favorable patient
      outcome, but several studies have established a tumor promotional role for AR,
      particularly in supporting the growth of estrogen receptor positive (ER-positive)
      breast cancers after endocrine therapy. Our previous studies have demonstrated
      that obesity promotes mammary tumor progression after ovariectomy (OVX) in a rat
      model of postmenopausal breast cancer. Here, we investigated a potential role for
      AR in obesity-associated post-OVX mammary tumor progression following ovarian
      estrogen loss. In this model, we found that obese but not lean rats had nuclear
      localized AR in tumors that progressed 3 weeks after OVX, compared to those that
      regressed. AR nuclear localization is consistent with activation of AR-dependent
      transcription. Longer-term studies (8 weeks post-OVX) showed that AR nuclear
      localization and expression were maintained in tumors that had progressed, but AR
      expression was nearly lost in tumors that were regressing. The anti-androgen
      enzalutamide effectively blocked tumor progression in obese rats by promoting
      tumor necrosis and also prevented the formation of new tumors after OVX. Neither
      circulating nor mammary adipose tissue levels of the AR ligand testosterone were
      elevated in obese compared to lean rats; however, IL-6, which we previously
      reported to be higher in plasma from obese versus lean rats, sensitized breast
      cancer cells to low levels of testosterone. Our study demonstrates that, in the
      context of obesity, AR plays a role in driving ER-positive mammary tumor
      progression in an environment of low estrogen availability, and that circulating
      factors unique to the obese host, including IL-6, may influence how cancer cells
      respond to steroid hormones.

PMID- 28741261
TI  - Hereditary breast cancer associated with Cowden syndrome-related PTEN mutation
      with Lhermitte-Duclos disease.
AB  - BACKGROUND: Cowden syndrome is characterized by multiple hamartomas in various
      tissues, including the skin, brain, breast, thyroid, mucous membrane, and
      gastrointestinal tract, and is reported to increase the risk of malignant
      disease. CASE PRESENTATION: We describe the case of a 52-year-old woman in whom a
      tumor was diagnosed in the left cerebellar hemisphere and treated by surgical
      resection. Phosphatase and tensin homolog (PTEN) mutation in exon 8 insertion was
      found in the brain tumor tissue and leukocytes. This finding supported the
      diagnosis of Cowden syndrome. She consequently developed endometrial cancer and
      underwent abdominal total hysterectomy with bilateral salpingo-oophorectomy. Four
      years later, hormone receptor-positive breast cancer was found in the right
      breast, and breast-conserving surgery with radiation therapy and sentinel lymph
      node biopsy was performed. CONCLUSIONS: Herein, we describe a patient who was
      diagnosed as having familial breast cancer associated with PTEN mutation-related
      Cowden syndrome. We also reviewed reports of this syndrome in the literature for
      disease appraisal.

PMID- 28741262
TI  - Maternal mental quality of life mediates the associations between intimate
      partner abuse against mothers and their children's behaviours and quality of life
      in low-income Chinese families.
AB  - PURPOSE: To explore the association between maternal intimate partner abuse (IPA)
      and their children's health-related quality of life (HRQOL) and behavioural
      problem, and to establish a mediation model and investigate the mediating role of
      mothers' HRQOL on this association. METHODS: A cross-sectional study was
      conducted on 197 mothers of 227 children (112 boys and 115 girls) from low-income
      Chinese families. The mothers were asked to complete the 5-item abuse assessment
      screen questionnaire for the presence of IPA, the Chinese (Hong Kong) version of
      12-item Short-Form Health Survey (SF-12) for their HRQOL and a structured socio
      demographics questionnaire. One of the parents completed the Child Health
      Questionnaire-Parent Form-50 (CHQ-PF50) and the strengths and difficulties
      questionnaire (SDQ) to report on their children's HRQOL and behavioural problems,
      respectively. The mediating effect of the maternal HRQOL on the relationship
      between maternal IPA status and their children's behavioural problems and HRQOL
      was tested using Baron and Kenney's multistage regression approach and
      bootstrapping method. RESULTS: Thirty-five of the 197 mothers reported IPA
      (17.8%). Children whose mothers had experienced IPA had lower scores in the CHQ
      PF50 mental health, parental impact-emotional, family activities and family
      cohesion subscales, and the psychosocial summary score compared to children of
      mothers who reported no IPA; they also had more emotional, conduct and
      hyperactivity/inattention problems and higher total difficulties scores measured
      by the SDQ. Maternal mental HRQOL was a mediator on the relationship between
      maternal IPA status and their children's behavioural problems and psychosocial
      HRQOL. CONCLUSION: IPA experienced by mothers had significant negative impacts on
      their children's HRQOL and behaviours, which was mediated by maternal mental
      HRQOL.

PMID- 28741264
TI  - Why Are Diabetes Medications So Expensive and What Can Be Done to Control Their
      Cost?
AB  - PURPOSE OF REVIEW: The purposes of this study were to describe how medication
      prices are established, to explain why antihyperglycemic medications have become
      so expensive, to show trends in expenditures for antihyperglycemic medications,
      and to highlight strategies to control expenditures in the USA. RECENT FINDINGS:
      In the U.S., pharmaceutical manufacturers set the prices for new products.
      Between 2002 and 2012, expenditures for antihyperglycemic medications increased
      from $10 billion to $22 billion. This increase was primarily driven by
      expenditures for insulin which increased sixfold. The increase in insulin
      expenditures may be attributed to several factors: the shift from inexpensive
      beef and pork insulins to more expensive genetically engineered human insulins
      and insulin analogs, dramatic price increases for the available insulins,
      physician prescribing practices, policies that limit payers' abilities to
      negotiate prices, and nontransparent negotiation of rebates and discounts. The
      costs of antihyperglycemic medications, especially insulin, have become a barrier
      to diabetes treatment. While clinical interventions to shift physician
      prescribing practices towards lower cost drugs may provide some relief, we will
      ultimately need policy interventions such as more stringent requirements for
      patent exclusivity, greater transparency in medication pricing, greater
      opportunities for price negotiation, and outcomes-based pricing models to control
      the costs of antihyperglycemic medications.

PMID- 28741263
TI  - Unmet Needs in the Pathogenesis and Treatment of Cardiovascular Comorbidities in
      Chronic Inflammatory Diseases.
AB  - The developments that have taken place in recent decades in the diagnosis and
      therapy of a number of diseases have led to improvements in prognosis and life
      expectancy. As a consequence, there has been an increase in the number of
      patients affected by chronic diseases and who can face new pathologies during
      their lifetime. The prevalence of chronic heart failure, for example, is
      approximately 1-2% of the adult population in developed countries, rising to
      >=10% among people >70 years of age; in 2015, more than 85 million people in
      Europe were living with some sort of cardiovascular disease (CVD) (Lubrano and
      Balzan World J Exp Med 5:21-32, 5; Takahashi et al. Circ J 72:867-72, 8; Kaptoge
      et al. Lancet 375:132-40, 9). Chronic disease can become, in turn, a major risk
      factor for other diseases. Furthermore, several new drugs have entered clinical
      practice whose adverse effects on multiple organs are still to be evaluated. All
      this necessarily involves a multidisciplinary vision of medicine, where the
      physician must view the patient as a whole and where collaboration between the
      various specialists plays a key role. An example of what has been said so far is
      the relationship between CVD and chronic inflammatory diseases (CIDs). Patients
      with chronic CVD may develop a CID within their lifetime, and, vice versa, a CID
      can be a risk factor for the development of CVD. Moreover, drugs used for the
      treatment of CIDs may have side effects involving the cardiovascular system and
      thus may be contraindicated. The purpose of this paper is to investigate the
      close relationship between these two groups of diseases and to provide
      recommendations on the diagnostic approach and treatments in light of the most
      recent scientific data available.

PMID- 28741265
TI  - Mechanisms of Type 2 Diabetes Risk Loci.
AB  - PURPOSE OF REVIEW: Deciphering the mechanisms of type 2 diabetes (T2DM) risk loci
      can greatly inform on disease pathology. This review discusses current knowledge
      of mechanisms through which genetic variants influence T2DM risk and
      considerations for future studies. RECENT FINDINGS: Over 100 T2DM risk loci to
      date have been identified. Candidate causal variants at risk loci map
      predominantly to non-coding sequence. Physiological, epigenomic and gene
      expression data suggest that variants at many known T2DM risk loci affect
      pancreatic islet regulation, although variants at other loci also affect protein
      function and regulatory processes in adipose, pre-adipose, liver, skeletal muscle
      and brain. The effects of T2DM variants on regulatory activity in these tissues
      appear largely, but not exclusively, due to altered transcription factor binding.
      Putative target genes of T2DM variants have been defined at an increasing number
      of loci and some, such as FTO, may entail several genes and multiple tissues.
      Gene networks in islets and adipocytes have been implicated in T2DM risk,
      although the molecular pathways of risk genes remain largely undefined. Efforts
      to fully define the mechanisms of T2DM risk loci are just beginning. Continued
      identification of risk mechanisms will benefit from combining genetic fine
      mapping with detailed phenotypic association data, high-throughput epigenomics
      data from diabetes-relevant tissue, functional screening of candidate genes and
      genome editing of cellular and animal models.

PMID- 28741266
TI  - Effect of Simulated Climate Warming on the Ectomycorrhizal Fungal Community of
      Boreal and Temperate Host Species Growing Near Their Shared Ecotonal Range
      Limits.
AB  - Ectomycorrhizal (ECM) fungi can influence the establishment and performance of
      host species by increasing nutrient and water absorption. Therefore,
      understanding the response of ECM fungi to expected changes in the global climate
      is crucial for predicting potential changes in the composition and productivity
      of forests. While anthropogenic activity has, and will continue to, cause global
      temperature increases, few studies have investigated how increases in temperature
      will affect the community composition of ectomycorrhizal fungi. The effects of
      global warming are expected to be particularly strong at biome boundaries and in
      the northern latitudes. In the present study, we analyzed the effects of
      experimental manipulations of temperature and canopy structure (open vs. closed)
      on ectomycorrhizal fungi identified from roots of host seedlings through 454
      pyrosequencing. The ecotonal boundary site selected for the study was between the
      southern boreal and temperate forests in northern Minnesota, USA, which is the
      southern limit range for Picea glauca and Betula papyrifera and the northern one
      for Pinus strobus and Quercus rubra. Manipulations that increased air and soil
      temperature by 1.7 and 3.4  degrees C above ambient temperatures, respectively,
      did not change ECM richness but did alter the composition of the ECM community in
      a manner dependent on host and canopy structure. The prediction that colonization
      of boreal tree species with ECM symbionts characteristic of temperate species
      would occur was not substantiated. Overall, only a small proportion of the ECM
      community appears to be strongly sensitive to warming.

PMID- 28741267
TI  - Can We Abandon Mediation? A Commentary on the Article "Theorizing with/out
      'Mediators'".
AB  - In view of the status of mediation as a long standing and widely used
      developmental principle, it is clear that theoretical challenging of mediation
      would have far reaching consequences. Therefore, it is assumed that the best
      strategy to respond to challenge would be to examine the solidity of foundations
      of both the principle of mediation and the suggested alternative non-mediational
      position. This strategy has determined the structure of the paper. First, it
      offers anthropological, cultural-historical, ontogenetic, microgenetic and
      epistemological foundations of the principle of mediation in order to justify its
      historical and theoretical status. In the second step, claims which challenge the
      necessity and fruitfulness of mediation as a developmental principle will be
      examined. Within the challenging strategy two argumentative patterns will be
      analysed: first, the validity of interpretation of mediation principle offered by
      its critics and second, explanatory potentials of non-mediational standpoints. In
      conclusion, it will be argued that the proposed non-mediational position does not
      offer sufficient justification for repudiation of mediation principle and
      adoption of an alternative non-mediational standpoint.

PMID- 28741268
TI  - Assessing Cancer Health Literacy among Spanish-Speaking Latinos.
AB  - Health literacy is a dynamic construct that changes with specific health
      conditions; thus, new disease-specific health literacy tools are needed. Since
      cancer is the leading cause of death among Latinos, the largest and fastest
      growing minority population in the nation, there is a need to develop tools to
      assess cancer health literacy (CHL) among the Spanish-speaking population. The
      Cancer Health Literacy Test, Spanish version (CHLT-30-DKspa) was applied to
      identify Spanish-speaking individuals with low CHL and ascertain which items in
      the tool best discriminate between CHL level groups. Cross-sectional field test
      of the CHLT-30-DKspa among Spanish-speaking Latinos. Latent class analysis (LCA)
      identified participants with varying CHL levels. Probability of correct answers,
      odds ratios, and standardized errors were used to identify the items that allow
      the classification of individuals among the latent classes. LCA resulted in a
      three-latent-class model predicting 39.4% of participants to be in the HIGH
      class, 43.3% in the MEDIUM class, and 17.3% in the LOW class. Eleven items (the
      CHLT-11-DKspa) meet the criteria to clearly separate participants with HIGH and
      LOW classes of CHL. Although the best model fit was a three-class solution,
      results showed a clear separation of individuals from HIGH versus LOW levels of
      CHL, but separation of those in the MEDIUM level was not as clear. The CHLT-11
      DKspa is a shorter measure that may be relatively easy to use in a clinical
      encounter to identify Spanish-speaking patients with the poorest levels of CHL
      who may require additional support to understand medical instructions and care
      plans.

PMID- 28741269
TI  - Prevention of HPV-Related Oral Cancer by Dentists: Assessing the Opinion of Dutch
      Dental Students.
AB  - The aim of this study is to assess dental students' opinions of the dentists'
      role in primary prevention of human papillomavirus (HPV)-related oral cancer
      using a cross-sectional web-based survey. A questionnaire, containing questions
      about knowledge of HPV and oral cancer, confidence in head and neck examination
      and role of the dentist in preventing HPV-related oral cancer, was sent to all
      students of the Academic Centre of Dentistry Amsterdam (n = 912). One hundred and
      twenty-six (n = 126) students completed the questionnaire. Significantly, more
      master students (75%) than bachelor students (54.3%) were aware that HPV is a
      causative factor for oral cancer. Master students had more knowledge of HPV than
      bachelor students, but knowledge about HPV vaccination was irrespective of the
      study phase. The majority of dental students agreed that it is important to
      discuss HPV vaccination with patients. Eighty-nine percent of the students think
      that more education about symptoms of oral cancer will increase screening for
      oral cancer. Development of a protocol for screening in dental practices was
      considered even more important. According to dental students, dentists should
      discuss HPV as a risk factor for oral cancer with patients. Future dentists are
      willing to be involved in both primary and secondary prevention of HPV-related
      oral cancer. Therefore, screening for oral cancer and education about HPV
      vaccination should be integral elements of the dental curriculum.

PMID- 28741271
TI  - Supplementation with branched-chain amino acids ameliorates hypoalbuminemia,
      prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of
      patients with liver cirrhosis.
AB  - BACKGROUND: Liver cirrhosis induces marked metabolic disorders, protein-energy
      malnutrition, and sarcopenia. The objective of the study reported here was to
      investigate the effects of dietary branched-chain amino acids (BCAAs) on systemic
      glucose metabolism, skeletal muscle, and prognosis of patients with liver
      cirrhosis. METHODS: Japanese patients with liver cirrhosis (n = 21) were enrolled
      into a longitudinal study in which their diets were supplemented with BCAAs. We
      evaluated glucose metabolism and analyzed the skeletal muscle area index (SAI)
      and intramuscular adipose tissue content (IMAC) using computed tomography.
      RESULTS: After 48 weeks of supplementation with BCAAs, there were no changes in
      glucose metabolism and skeletal muscle findings. In patients with ameliorated
      hypoalbuminemia, IMAC was significantly decreased and SAI was preserved
      concomitant with decreasing 90- and 120-min post-challenge plasma glucose levels
      (P < 0.01 each). In patients without increased albumin levels, IMAC was
      significantly increased and the SAI was significantly decreased (P < 0.01 each).
      Liver-related event-free survival rates for 72 months were 63.6% in patients with
      decreased IMAC and 20.0% in patients with increased IMAC. CONCLUSIONS:
      Amelioration of hypoalbuminemia associated with BCAA supplementation correlated
      with decreased fat accumulation in skeletal muscle, maintenance of skeletal
      muscle mass, and improved glucose sensitivity, all factors which may contribute
      to improving the survival of patients with liver cirrhosis.

PMID- 28741270
TI  - Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty
      liver disease.
AB  - BACKGROUND AND AIMS: The risk factors in the progression of nonalcoholic fatty
      liver disease (NAFLD) have not been fully clarified. Porphyromonas gingivalis
      (P.g) has been considered to be a confounding risk factor for systemic diseases.
      We aimed to evaluate the effect of P.g infection on risk of progression to NASH.
      METHODS: (1) Serum IgG antibody titers against P.g fimbriae (fimA) in 200 biopsy
      proven NAFLD patients were measured by ELISA and compared with histological
      findings. (2) C57BL/6J mice were fed a control diet (CD) or high-fat diet (HFD)
      with or without P.g-odontogenic infection and analyzed histologically. Mouse
      livers were analyzed using CE-TOFMS and LC-TOFMS. RESULTS: (1) A significant
      correlation between fibrosis progression and antibody titers against P.g
      possessing fimA type 4 was identified (P = 0.0081). Multivariate analysis
      identified older age and type 4 P.g-positivity as risk factors for advanced
      fibrosis. (2) Fibrosis and steatosis were more severe in HFD P.g(+) mice compared
      with HFD P.g(-) mice. In metabolome analysis, fatty acid metabolism was
      significantly disrupted with HFD in P.g-infected mouse livers.
      Monounsaturated/saturated fatty acid ratios were significantly higher in the HFD
      P.g(+) group than in the HFD P.g(-) group (P < 0.05). Moreover, expression levels
      of SCD1 and ELOVL6 were significantly reduced. CONCLUSIONS: These results suggest
      that P.g infection is an important risk factor for pathological progression in
      NAFLD. Increase in the monounsaturated/saturated fatty acid ratio may be an
      important change that facilitates progression of NAFLD.

PMID- 28741272
TI  - An up-down determination of the required seated duration after intrathecal
      injection of bupivacaine and fentanyl for the prevention of hypotension during
      Cesarean delivery.
AB  - PURPOSE: A prolonged seated time after intrathecal injection of hyperbaric
      bupivacaine and morphine is related to the incidence of hypotension during
      Cesarean delivery, but results in a high incidence of pain during peritoneal
      closure. We conducted this study to determine the effect of the addition of
      intrathecal fentanyl on the relationship between seated time and hypotension and
      intraoperative analgesia requirements. METHODS: Women undergoing Cesarean
      delivery were randomized to receive an intrathecal injection of either 11.25 or
      15 mg of hyperbaric bupivacaine with morphine 150 ug and fentanyl 15 ug using a
      combined spinal-epidural technique. The seated duration following intrathecal
      injection was assigned using up-down methodology. If the preceding patient was
      hypo- or normotensive, the next patient sat for 15 sec more or less,
      respectively. A systolic blood pressure < 80% of the preoperative value was
      defined as hypotension; a standardized anesthetic was administered, and the
      presence of pain during the procedure was recorded. Isotonic regression of pooled
      adjacent violators was used to determine the time at which 50% of each group
      would avoid hypotension (i.e., the median effective seated time). RESULTS: There
      were 15 patients in each group. The median seated time was 129 sec (95%
      confidence interval [CI], 116 to 150) for the 11.25-mg group and 459 sec (95% CI,
      444 to 471) for the 15-mg group. Only one (3%) of the 30 patients in the study
      had pain on peritoneal closure, and this was successfully treated with
      intravenous fentanyl. CONCLUSION: We have determined the seated time required
      following intrathecal injection of hyperbaric bupivacaine, morphine, and fentanyl
      to prevent hypotension in 50% of patients undergoing Cesarean delivery. TRIAL
      REGISTRATION: www.clinicaltrials.gov , NCT01896960. Registered 2 July 2013.

PMID- 28741273
TI  - Can a hand radiograph indicate a special diagnosis in a child with chronic kidney
      disease? Answers.

PMID- 28741274
TI  - Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib,
      and abemaciclib.
AB  - PURPOSE: The cyclin D-cyclin dependent kinase (CDK) 4/6-inhibitor of CDK4 (INK4)
      retinoblastoma (Rb) pathway plays a crucial role in cell cycle progression and
      its dysregulation is an important contributor to endocrine therapy resistance.
      CDK4/6 inhibitors trigger cell cycle arrest in Rb protein (pRb)-competent cells.
      Recent years have seen the development of selective CDK4/6 inhibitors, which have
      delivered promising results of efficacy and manageable safety profiles. The main
      objective of this review is to discuss preclinical and clinical data to date, and
      ongoing clinical trials with palbociclib, ribociclib, and abemaciclib in breast
      cancer. METHODS: A literature search of above topics was carried out using PubMed
      and data reported at international oncology meetings and clinicaltrials.gov were
      included. RESULTS: The highly selective oral CDK4/6 inhibitors have been tested
      in combination with endocrine therapy in Phase III studies in metastatic breast
      cancer. Results led to the US Food and Drug Administration approval of
      palbociclib (PD0332991) and ribociclib (LEE011), and abemaciclib (LY2835219) is
      in development. Studies of these agents, in combination with endocrine therapy,
      are also underway in ER-positive early breast cancer in the neoadjuvant and
      adjuvant settings. Moreover, they are also being investigated with other agents
      in the advanced setting and in triple negative breast cancer. CONCLUSIONS: After
      having demonstrated impressive activity in ER-positive, HER2-negative metastatic
      breast cancer, currently CDK4/6 inhibitors are in further development. It is
      obvious that this class of agents with their efficacy, low and easily manageable
      toxicity, and oral dosage is a very important treatment option for breast cancer
      patients.

PMID- 28741275
TI  - Fatty liver decreases the risk of liver metastasis in patients with breast
      cancer: a two-center cohort study.
AB  - BACKGROUND: The influence of hepatic steatosis (HS) on liver metastasis in
      patients with non-metastatic breast cancer (BC) remains unclear. The aim of this
      study was to clarify the relationship between HS and liver metastasis in non
      metastatic BC patients. METHODS: Patients who underwent treatment for BC at two
      affiliated hospitals of Southern Medical University, between January 1, 2005 and
      December 31, 2015, were retrospectively reviewed. BC patients were divided into
      the study and control groups based on the presence of HS. The association between
      HS and liver metastasis was analyzed, adjusting for the confounding factors using
      Cox regression and propensity score case-match analysis. RESULTS: In total, 1230
      female BC patients were included, and 372 (30.2%) patients were diagnosed with HS
      (at the time of diagnosis BC or before). The cumulative liver metastasis-free
      survival (MFS) rate was significantly higher in the study group than in the
      control group (hazard ratio 0.61; 95% confidence interval 0.40-0.94; P = 0.024).
      On multivariate analysis, HS was an independent protective factor for local liver
      metastasis (HR 0.55; 0.35-0.86; P = 0.008). After one-to-one matching of the
      study group (344) with the control group (344), liver MFS remained significantly
      better in the study group (HR 0.42; 0.26-0.69; P = 0.001). CONCLUSION: This study
      indicated that HS may serve as an independent factor to decrease liver metastasis
      in patients with BC. Additional prospective studies are necessary to validate
      this finding.

PMID- 28741276
TI  - The use of a biphasic calcium phosphate in a maxillary sinus floor elevation
      procedure: a clinical, radiological, histological, and histomorphometric
      evaluation with 9- and 12-month healing times.
AB  - BACKGROUND: This study evaluates the clinical, radiological, histological, and
      histomorphometric aspects of a fully synthetic biphasic calcium phosphate (BCP)
      (60% hydroxyapatite and 40% beta-tricalcium phosphate), used in a human maxillary
      sinus floor elevation (MSFE) procedure with 9- and 12-month healing time.
      METHODS: A unilateral MSFE procedure, using 100% BCP, was performed in two series
      of five patients with healing times of 9 and 12 months respectively. Clinical and
      radiological parameters were measured up to 5 years postoperatively. Biopsy
      retrieval was carried out during dental implants placement. Histology and
      histomorphometry were performed on 5-MUm sections of undecalcified bone biopsies.
      RESULTS: The MSFE procedure with BCP showed uneventful healing in all cases. All
      dental implants appeared to be well osseointegrated after 3 months. Radiological
      evaluation showed less than 1 mm tissue height loss from MSFE to the 5-year
      follow-up examination. No signs of inflammation were detected on histological
      examination. Newly formed mineralized tissue was found cranially from the native
      bone. The BCP particles were surrounded by connective tissue, osteoid islands,
      and newly formed bone. Mineralized bone tissue was in intimate contact with the
      BCP particles. After 12 months, remnants of BCP were still present. The newly
      formed bone had a trabecular structure. Bone maturation was demonstrated by the
      presence of lamellar bone. Histomorphometric analysis showed at 9 and 12 months
      respectively an average vital bone volume/total volume of 35.2 and 28.2%, bone
      surface/total volume of 4.2 mm2/mm3 and 8.3 mm2/mm3, trabecular thickness of
      224.7 and 66.7 MUm, osteoid volume/bone volume of 8.8 and 3.4%, osteoid
      surface/bone surface (OS/BS) of 42.4 and 8.2%, and osteoid thickness of 93.9 and
      13.6 MUm. CONCLUSIONS: MFSE with BCP resulted in new bone formation within the
      augmented sinus floor and allowed the osseointegration of dental implants in both
      groups. From a histological and histomorphometric perspective, a 9-month healing
      time for this type of BCP may be the optimal time for placement of dental
      implants.

PMID- 28741277
TI  - Analysis of Subjects' Vulnerability in a Touch Screen Game Using Behavioral
      Metrics.
AB  - In this article, we report results on an experimental study conducted with
      volunteer subjects playing a touch-screen game with two unique difficulty levels.
      Subjects have knowledge about the rules of both game levels, but only sufficient
      playing experience with the easy level of the game, making them vulnerable with
      the difficult level. Several behavioral metrics associated with subjects' playing
      the game are studied in order to assess subjects' mental-workload changes induced
      by their vulnerability. Specifically, these metrics are calculated based on
      subjects' finger kinematics and decision making times, which are then compared
      with baseline metrics, namely, performance metrics pertaining to how well the
      game is played and a physiological metric called pnn50 extracted from heart rate
      measurements. In balanced experiments and supported by comparisons with baseline
      metrics, it is found that some of the studied behavioral metrics have the
      potential to be used to infer subjects' mental workload changes through different
      levels of the game. These metrics, which are decoupled from task specifics,
      relate to subjects' ability to develop strategies to play the game, and hence
      have the advantage of offering insight into subjects' task-load and vulnerability
      assessment across various experimental settings.

PMID- 28741279
TI  - Identification of Lead Molecules in Garcinia mangostana L. Against Pancreatic
      Cholesterol Esterase Activity: An In Silico Approach.
AB  - Hypercholesterolemia is one of the major risk factors for the development and
      progression of atherosclerosis. Hence, inhibitors of cholesterol absorption have
      been investigated for decades as a strategy to prevent and treat cardiovascular
      diseases associated with hypercholesterolemia. Cholesterol esterase (CEase) in
      pancreatic juice plays a vital role in the hydrolysis of dietary cholesterol
      esters to cholesterol and fatty acids. Since inhibition of CEase might lead to a
      reduction of cholesterol absorption, an attempt is made in this study to identify
      lead molecules of Garcinia mangostana by the in silico approach. The study
      employed software applications viz., AutoDock 4.2 and GOLD Suite of Programs 5.2.
      The study revealed the efficacy of three compounds viz., epicatechin, euxanthone,
      and 1,3,5,6-tetrahydroxy-xanthone, which exhibited least binding energy in
      AutoDock and moderate scoring in GOLD. The molecular properties as well as
      biological activity of these three compounds were predicted by molinspiration
      prediction tool. The results show the crucial role of polyphenolic compounds to
      limit the activity of CEase. The drug-likeness prediction revealed the prospects
      of the identified lead molecules as potential drug candidates.

PMID- 28741278
TI  - Italian intersociety consensus on prevention, diagnosis, and treatment of
      delirium in hospitalized older persons.
AB  - Delirium is a severe neuropsychiatric syndrome characterized by inattention and
      global cognitive dysfunction in the setting of an acute medical illness, medical
      complication, drug intoxication, or drug withdrawal. The most important risk
      factors are advanced age and dementia, whereas pain, dehydration, infections,
      stroke, metabolic disturbances, and surgery are the most common triggering
      factors. Although delirium is a common clinical syndrome in different settings of
      care (acute care hospitals, inpatient rehabilitation facilities, nursing homes,
      and hospices), it often remains under-recognized, poorly understood, and
      inadequately managed. There exists a clear need for improved understanding to
      overcome cultural stereotypes, and for the development and dissemination of a
      comprehensive model of implementation of general good practice points. A network
      of Italian national scientific societies was thus convened (1) to develop a
      collaborative multidisciplinary initiative report on delirium in elderly
      hospitalized patients, (2) to focus the attention of health care personnel on
      prevention, diagnosis, and therapy of patients suffering from delirium, and (3)
      to make the health services research community and policy-makers more aware of
      the potential risks of this condition providing a reference for training
      activities and data collection.

PMID- 28741280
TI  - Energy expenditure in the etiology of human obesity: spendthrift and thrifty
      metabolic phenotypes and energy-sensing mechanisms.
AB  - The pathogenesis of human obesity is the result of dysregulation of the
      reciprocal relationship between food intake and energy expenditure (EE), which
      influences daily energy balance and ultimately leads to weight gain. According to
      principles of energy homeostasis, a relatively lower EE in a setting of energy
      balance may lead to weight gain; however, results from different study groups are
      contradictory and indicate a complex interaction between EE and food intake which
      may differentially influence weight change in humans. Recently, studies
      evaluating the adaptive response of one component to perturbations of the other
      component of energy balance have revealed both the existence of differing
      metabolic phenotypes ("spendthrift" and "thrifty") resulting from overeating or
      underfeeding, as well as energy-sensing mechanisms linking EE to food intake,
      which might explain the propensity of an individual to weight gain. The purpose
      of this review is to debate the role that human EE plays on body weight
      regulation and to discuss the physiologic mechanisms linking EE and food intake.
      An increased understanding of the complex interplay between human metabolism and
      food consumption may provide insight into pathophysiologic mechanisms underlying
      weight gain, which may eventually lead to prevention and better treatment of
      human obesity.

PMID- 28741281
TI  - Microglial depletion and activation: A [11C]PBR28 PET study in nonhuman primates.
AB  - BACKGROUND: The 18-kDa translocator protein (TSPO) is an important target for
      assessing neuroimmune function in brain with positron-emission tomography (PET)
      imaging. The goal of this work was to assess two [11C]PBR28 imaging paradigms for
      measuring dynamic microglia changes in Macaca mulatta. METHODS: Dynamic
      [11C]PBR28 PET imaging data with arterial blood sampling were acquired to
      quantify TSPO levels as [11C]PBR28 V T. Scans were acquired at three timepoints:
      baseline, immediately post-drug, and prolonged post-drug. RESULTS: In one animal,
      a colony-stimulating factor 1 receptor kinase inhibitor, previously shown to
      deplete brain microglia, reduced [11C]PBR28 V T in brain by 46 +/- 3% from
      baseline, which recovered after 12 days to 7 +/- 5% from baseline. In a different
      animal, acute lipopolysaccharide administration, shown to activate brain
      microglia, increased [11C]PBR28 V T in brain by 39 +/- 9% from baseline, which
      recovered after 14 days to -11 +/- 3% from baseline. CONCLUSIONS: These studies
      provide preliminary evidence of complementary paradigms to assess microglia
      dynamics via in vivo TSPO imaging.

PMID- 28741282
TI  - Reproductive Health Concerns among Substance-Using Women in Community Corrections
      in New York City: Understanding the Role of Environmental Influences.
AB  - Women living in urban settings who are engaged in the criminal justice system are
      disproportionately affected by HIV and also contend with poor sexual and
      reproductive health (SRH). While studies have examined environmental influences
      of HIV, few have examined how these influences relate to poor SRH among this
      population. We used baseline data from an HIV-risk reduction study among
      substance-using women with a pregnancy history in community corrections in New
      York City (N = 299). We examined risk environment factors typically associated
      with HIV, and SRH outcomes of abortion, and miscarriage. We used logistic
      regression models to examine associations between risk environment factors with
      SRH outcomes. Most women identified as black and ranged in age from 18 to 62.
      Approximately half had miscarriages and/or abortions in their lifetime. Few women
      used birth control despite not wanting children in the future. While most women
      faced high rates of environmental influences of HIV risk, only intimate partner
      violence (IPV) was associated with SRH outcomes. Women experiencing IPV were
      significantly more likely to report both miscarriage and abortion. Community
      corrections present a unique opportunity for intervention around HIV risk
      reduction and SRH outcomes, given that effective programming for each often
      requires multiple and formal contacts with health providers.

PMID- 28741284
TI  - Erratum to: Recovery from eating disorder 1 year after start of treatment is
      related to better mentalization and strong reduction of sensitivity to others.

PMID- 28741283
TI  - Caring for Young Children with Asthma: Perspectives from Urban Community Health
      Centers.
AB  - Asthma disproportionately affects low-income, minority youth, with notable
      disparities among children <5 years of age. Understanding the perceptions of
      urban community health centers (CHCs) regarding treating young children with
      asthma could improve care for these patients. This study uses data from semi
      structured focus groups with staff from eight urban CHCs. Themes emerged in three
      domains. Within the parent/family domain, providers noted low rates of follow-up
      visits, low health literacy, and-for young children specifically-misunderstanding
      about the diagnosis. At the CHC level, providers needed more staff, space, and
      comfort with applying the guidelines to infants and young children. CHCs reported
      asthma registries, population health oversight, and an asthma champion improved
      care. At the system level, providers wanted improved communication with emergency
      departments and community outreach programs. Reducing these multi-level barriers
      may improve care.

PMID- 28741285
TI  - Orthorexia vs. theories of healthy eating.

PMID- 28741286
TI  - Interleukin 6 receptor (IL-6R) was an independent prognostic factor in cervical
      cancer.
AB  - IL-6 has been found to be associated with poor response to chemoradiotherapy and
      poor overall prognosis of patients with cervical cancer. However, little is known
      about the clinicopathological significance of IL-6 receptor (IL-6R) expression in
      the setting of cervical cancer. To investigate the clinicopathological meaning of
      IL-6R in cervical cancer, expression of IL-6R was detected using
      immunohistochemistry in cervical cancer tissue microarray composed of 98 cases of
      cervical cancer and paired normal controls. As further confirmation of expression
      trend, western-blotting was conducted in another independent 36 pairs of cervical
      cancer and matched normal controls. Subsequently, the statistical correlation
      between IL-6R expression and clinicopathological variables was analyzed,
      including demographic, TNM stage, clinical grading and overall prognosis. IL-6R
      expression was shown to be remarkably associated with lymph node metastasis,
      recurrence and overall prognosis. Moreover, only IL-6R expression was observed to
      be an independent prognostic factor among these variables that could potentially
      influence the overall prognosis of patients with cervical cancer. In conclusion,
      IL-6R was shown to be an independent prognostic factor for patients with cervical
      cancer.

PMID- 28741287
TI  - Redefining Successful Treatment of Severe Alcoholic Hepatitis.

PMID- 28741288
TI  - Tuning the Spin Coupling Interactions in the Nitroxide-Based Bisphenol-Like
      Diradicals.
AB  - The intramolecular spin coupling interactions of bisphenol-like trinary-bridged
      diradicals [nitroxide-(para/meta)phenylene-X-phenylene(para/meta)-nitroxide,
      X=C=CH2 , O, BH, NH and SO2 ] were explored with an emphasis on the tuning role
      of the X coupler at the (U)B3LYP/6-311++G(d,p) level. Our results indicate that
      all designed trinary-bridged diradicals featuring a V-type structure with a
      bending angle of 104-130 degrees  and torsional angles of two phenylene rings
      being 20-90 degrees  exhibit different diradical character and magnetism,
      depending on the structures and properties of the X bridges. More interestingly,
      although meta/para-phenylene supports a ferromagnetic (FM)/antiferromagnetic
      (AFM) coupling, their combinations by using X as a trinary bridge can mediate
      spin coupling, but the coupling magnitude strongly depends on X. In general, a
      para/para or meta/meta combination with X leads to an open-shell singlet ground
      state and thus AFM, but the meta/meta combination considerably decreases the spin
      coupling interaction. In contrast, a para/meta combination with X produces a
      triplet ground state and FM. Their combination with a single-electron conjugation
      end coupler (C=CH2 ) leads to an inverse coupling regularity. All results can be
      reasonably explained by the spin alternation rule, molecular structures, and
      properties. In particular, detailed spin coupling mechanisms are suggested to
      involve cooperative through-space and through-bond pathways with different levels
      of cooperativity. This is rationalized with the X-induced bending of the
      diradicals not only modifying the through-bond (extended pi conjugation) pathway
      but also provididng a through-space (face-to-face vs. side-to-side pi-pi
      interaction) possibility for spin coupling, in conjunction with twisting of the
      phenylene rings. Different contributions of the through-space and through-bond
      couplings are quantitatively distinguished and depend on the structure and
      property of the X coupler. Clearly, this work reports interesting aspects of the
      trinary bridged diradicals and also provides important information for the design
      of molecules for functional magnetic materials and tuning their magnetic
      properties.

PMID- 28741289
TI  - Reply.

PMID- 28741291
TI  - Is Personality Associated with Secondhand Harm from Drinking?
AB  - BACKGROUND: Prior research suggests more than 70% of undergraduates have
      experienced harm from other students' drinking. This study built on the
      literature by, first, investigating whether secondhand harm cluster into latent
      factors that reflect distinct but related types of harm. Second, given the
      paucity of research examining factors that increase students' vulnerability to
      secondhand harm, we examined dimensions from Castellanos-Ryan and Conrod's 4
      factor personality model for alcohol disorders (impulsivity [IMP], sensation
      seeking [SS], hopelessness [HOP], anxiety sensitivity [AS]) as predictors of
      secondhand harm exposure. We also investigated the possible mediating role of
      students' own problematic alcohol use in explaining personality-secondhand harm
      relationships. METHODS: An online survey was administered to 1,537 first-year
      Canadian undergraduates (68% women). Problematic alcohol use was measured by the
      Alcohol Use Disorders Identification Test, and personality was measured by the
      Substance Use Risk Profile Scale. Eleven secondhand harm items were included.
      RESULTS: The secondhand harm clustered into 3 distinct but related factors:
      "strains" (e.g., interruption of sleep or study), "threats" (e.g., harassment or
      assault), and "interpersonal harm" (e.g., arguments with peers). Sixty-eight
      percent of respondents reported strains, 44% threats, and 64% interpersonal harm,
      and 35% reported experiencing all 3 types of harm, in the last term. All 4
      personality dimensions were independently associated with greater secondhand harm
      exposure. HOP was directly associated with threats and interpersonal harm, and AS
      was directly associated with all 3 types of harm. SS and IMP were both indirectly
      associated with all 3 types of harm through students' own problematic alcohol
      use. In addition, IMP was directly related to threats. CONCLUSIONS: The
      prevalence of secondhand harm from alcohol is high among undergraduates. Findings
      suggest that distinct personality risks may predispose students to experience
      secondhand harm, albeit perhaps through different mechanisms. Implications for
      future research, prevention, and policy development are discussed.

PMID- 28741290
TI  - Biochemical Characterization of the Lysine Acetylation of Tyrosyl-tRNA Synthetase
      in Escherichia coli.
AB  - Aminoacyl-tRNA synthetases (aaRSs) play essential roles in protein synthesis. As
      a member of the aaRS family, the tyrosyl-tRNA synthetase (TyrRS) in Escherichia
      coli has been shown in proteomic studies to be acetylated at multiple lysine
      residues. However, these putative acetylation targets have not yet been
      biochemically characterized. In this study, we applied a genetic-code-expansion
      strategy to site-specifically incorporate Nepsilon -acetyl-l-lysine into selected
      positions of TyrRS for in vitro characterization. Enzyme assays demonstrated that
      acetylation at K85, K235, and K238 could impair the enzyme activity. In vitro
      deacetylation experiments showed that most acetylated lysine residues in TyrRS
      were sensitive to the E. coli deacetylase CobB but not YcgC. In vitro acetylation
      assays indicated that 25 members of the Gcn5-related N-acetyltransferase family
      in E. coli, including YfiQ, could not acetylate TyrRS efficiently, whereas TyrRS
      could be acetylated chemically by acetyl-CoA or acetyl-phosphate (AcP) only. Our
      in vitro characterization experiments indicated that lysine acetylation could be
      a possible mechanism for modulating aaRS enzyme activities, thus affecting
      translation.

PMID- 28741292
TI  - Effect of MDP-Based Silane and Different Surface Conditioner Methods on Bonding
      of Resin Cements to Zirconium Framework.
AB  - PURPOSE: To determine the shear bond strength (SBS) between zirconium framework
      and resin cements after different surface conditioner methods and after
      application of 10-methacryloyloxydecyl dihydrogen phosphate (MDP) based silane
      and a bonding agent mix. MATERIALS AND METHODS: 128 disc-shaped zirconium-oxide
      specimens were prepared. Specimens were placed in autopolymerizing acrylic resin.
      The bonding surface of specimens was smoothed consecutively with 600-, 800-, and
      1200-grit silicon carbide papers under water cooling. Eight groups were prepared:
      CJ, Co-Jet; N, Nd-YAG laser; E, Er-YAG laser; NS, Nd-YAG laser + silane; ES, Er
      YAG laser + silane; CJB, Co-Jet + bonding agent; NSB, Nd-YAG laser + silane +
      bonding agent; ESB, Er-YAG laser + silane + bonding agent. SEM analysis was
      performed under 2000* magnification. Dual- and self-cured resin cements were
      bonded to specimens, and shear force was applied. Data were analyzed with one-way
      ANOVA and Tukey's multiple comparison test (p < 0.05). RESULTS: The SBS values
      differed from each other among the groups. While the CJB group showed the highest
      values, the N group showed the lowest. The treatment with MDP-based silane and
      bonding agent mix increased SBS values of each cement belonging to each group. SB
      values of dual-cure resin cement were higher than those of self-cure resin
      cements. CONCLUSION: Different surface conditioner methods exhibit an important
      effect on the SBS of resin cements to zirconium. The application of MDP-based
      silane and bonding agent mix enhanced SB values.

PMID- 28741293
TI  - The 2016 Most Influential Bioelectromagnetics Journal Paper by Citation Award.

PMID- 28741294
TI  - Magnetic resonance elastography assessment of fibrosis in children with NAFLD:
      Promising but not perfect.

PMID- 28741295
TI  - Early segmental relaxation abnormalities in hypertrophic cardiomyopathy for
      differential diagnostic of patients with left ventricular hypertrophy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left
      ventricular hypertrophy (LVH). However, clinical signs can be subtle and
      differentiation from other causes of LVH is challenging. HYPOTHESIS: As diastolic
      dysfunction (DD) is an early sign in HCM, we aimed to find regional changes in
      relaxation pattern for differentiation from other entities of LVH. METHODS: In
      148 patients (81 HCM, 55 arterial hypertension (AHT), 12 Fabry disease) and 63
      healthy controls, relaxation patterns were assessed using regional tissue Doppler
      imaging. In 42 HCM patients, myocardial mass and fibrosis were quantified by
      cardiac magnetic resonance imaging and correlated with relaxation parameters.
      RESULTS: In HCM the septal to lateral isovolumic relaxation time (s/l IVRT) ratio
      was higher (1.5 +/- 0.4) compared with AHT (1.1 +/- 0.2), Fabry disease (1.0 +/-
      0.1), and controls (1.1 +/- 0.2; P < 0.001), showing 77% sensitivity and 79%
      specificity to discriminate HCM-related LVH from other entities. The s/l IVRT
      ratio was independent of global DD in HCM (HCM with DD: 1.5 +/- 0.5, n = 52; HCM
      without DD: 1.5 +/- 0.3, n = 29) and remained significantly different from other
      entities in a subgroup of HCM patients with maximum wall thickness < 20 mm (s/l
      ratio: 1.5 +/- 0.5, n = 28). Regional IVRT did not correlate with the
      corresponding segmental myocardial mass or amount of fibrosis in cardiac magnetic
      resonance imaging. CONCLUSIONS: HCM patients show a prolonged septal IVRT
      irrespective of the extent of LVH and even before developing global DD. The s/l
      IVRT ratio is significantly higher in HCM compared with AHT or Fabry disease,
      thus establishing segmental IVRT analysis as a potential parameter for
      differential diagnosis in LVH.

PMID- 28741296
TI  - Homoleptic Alkynyl-Protected Gold Nanoclusters: Au44 (PhC=C)28 and Au36
      (PhC=C)24.
AB  - For the first time total structure determination of homoleptic alkynyl-protected
      gold nanoclusters is reported. The nanoclusters are synthesized by direct
      reduction of PhC=CAu, to give Au44 (PhC=C)28 and Au36 (PhC=C)24 . The Au44 and
      Au36 nanoclusters have fcc-type Au36 and Au28 kernels, respectively, as well as
      surrounding PhC=C-Au-C2 (Ph)Au-C=CPh dimeric "staples" and simple PhC=C bridges.
      The structures of Au44 (PhC=C)28 and Au36 (PhC=C)24 are similar to Au44 (SR)28
      and Au36 (SR)24 , but the UV/Vis spectra are different. The protecting ligands
      influence the electronic structures of nanoclusters significantly. The synthesis
      of these two alkynyl-protected gold nanoclusters indicates that a series of gold
      nanoclusters in the general formula Aux (RC=C)y as counterparts to Aux (SR)y can
      be expected.

PMID- 28741297
TI  - MALDI-FT-ICR-MS for archaeological lipid residue analysis.
AB  - Soft-ionization methods are currently at the forefront of developing novel
      methods for analysing degraded archaeological organic residues. Here, we present
      little-used soft ionization method of matrix assisted laser desorption/ionization
      Fourier transform-ion cyclotron resonance-mass spectrometry (MALDI-FT-ICR-MS) for
      the identification of archaeological lipid residues. It is a high-resolution and
      sensitive method with low limits of detection capable of identifying lipid
      compounds in small concentrations, thus providing a highly potential new
      technique for the analysis of degraded lipid components. A thorough methodology
      development for analysing cooked and degraded food remains from ceramic vessels
      was carried out, and the most efficient sample preparation protocol is described.
      The identified components, also controlled by independent parallel analysis by
      gas chromatography-mass spectrometry (GC-MS) and gas chromatography-combustion
      isotope ratio mass spectrometry (GC-C-IRMS), demonstrate its capability of
      identifying very different food residues including dairy, adipose fats as well as
      lipids of aquatic origin. The results obtained from experimentally cooked and
      original archaeological samples prove the suitability of MALDI-FT-ICR-MS for
      analysing archaeological organic residues. Sample preparation protocol and
      identification of compounds provide future reference for analysing various aged
      and degraded lipid residues in different organic and mineral matrices.

PMID- 28741298
TI  - Interferon lambda 4 rs368234815 TT>deltaG variant is associated with liver damage
      in patients with nonalcoholic fatty liver disease.
AB  - : The interferon (IFN) lambda 3/4 (IFNL3/4) locus, influencing innate immunity
      regulation, has been associated with the severity of hepatitis and fibrosis
      progression during chronic hepatitis C infection, while contrasting results were
      reported in nonalcoholic fatty liver disease. In this study, we examined whether
      rs12979860 and the linked causal rs368234815 variant encoding for the alternative
      IFNL4 protein variant are associated with liver fibrosis and damage in a large
      multicenter cohort of patients at risk of nonalcoholic steatohepatitis. To
      clarify the mechanism, we also evaluated the impact on IFN-stimulated gene
      hepatic expression in a subset of patients. We considered 946 consecutive Italian
      individuals at risk of nonalcoholic steatohepatitis with liver histology
      evaluated according to Kleiner. The rs368234815 TT>deltaG, rs12979860 C>T, and
      patatin-like phospholipase-3 rs738409 C>G polymorphisms were genotyped; and IFN
      stimulated gene hepatic expression (n = 16) was tested by TaqMan assays. We found
      that the rs368234815 TT allele was independently associated with severe F3-F4
      fibrosis (odds ratio, 1.53; 95% confidence interval, 1.15-2.31; P = 0.005) and
      with severe (grade 2-3) lobular necroinflammation (odds ratio, 1.47; 95%
      confidence interval, 1.14-1.88; P = 0.002). The impact of rs368234815 on liver
      damage was generally more marked in nonobese individuals, where association with
      severe fibrosis, necroinflammation, and nonalcoholic steatohepatitis was observed
      (P < 0.05). IFN-stimulated genes were hypo-expressed in the liver of patients
      carrying the IFNL4 rs368234815 TT/TT genotype (P < 0.05). Similar results were
      observed when considering the rs12979860 polymorphism, which was in high linkage
      disequilibrium with rs368234815 (R2 = 0.87). CONCLUSION: The IFNL4 genotype is
      associated with severity of fibrosis in nonalcoholic fatty liver disease patients
      of European ancestry, likely by modulating the activation of innate immunity and
      necroinflammation. (Hepatology 2017;66:1885-1893).

PMID- 28741300
TI  - Catalytic Mechanism of the Hotdog-Fold Thioesterase PA1618 Revealed by X-ray
      Structure Determination of a Substrate-Bound Oxygen Ester Analogue Complex.
AB  - Thioesterase activity accounts for the majority of the activities in the hotdog
      fold superfamily. The structures and mechanisms of catalysis for many hotdog
      enzymes have been elucidated by X-ray crystallography and kinetics to probe the
      specific substrate usage and cellular functions. However, structures of hotdog
      thioesterases in complexes with substrate analogues reported to date utilize
      ligands that either represent truncations of the substrate or include additional
      atoms to prevent hydrolysis. Here we present the synthesis of an isosteric and
      isoelectronic substrate analogue-benzoyl-OdCoA-and the X-ray crystal structure of
      a complex of the analogue with Pseudomonas aeruginosa hotdog thioesterase PA1618
      (at 1.72 A resolution). The complex is compared with that of the "imperfect"
      substrate analogue phenacyl-CoA, refined to a resolution of 1.62 A. Kinetic and
      structural results are consistent with Glu64 as the catalytic residue and with
      the involvement of Gln49 in stabilization of the transition state. Structural
      comparison of the two ligand-bound structures revealed a crucial ordered water
      molecule coordinated in the active site of the benzoyl-OdCoA structure but not
      present in the phenacyl-CoA-bound structure. This suggests a general base
      mechanism of catalysis in which Glu64 activates the coordinated water
      nucleophile. Together, our findings reveal the importance of a closely similar
      substrate analogue to determine the true substrate binding and catalytic
      mechanism.

PMID- 28741301
TI  - Intravenous Acetaminophen for Analgesia: Back to Square One.

PMID- 28741299
TI  - A Review of Moxifloxacin for the Treatment of Drug-Susceptible Tuberculosis.
AB  - Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of
      multidrug-resistant tuberculosis and is being investigated in novel drug regimens
      with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment
      of drug-susceptible tuberculosis. Early results of these studies are promising.
      Although current evidence does not support the use of moxifloxacin in treatment
      shortening regimens for drug-susceptible tuberculosis, it may be recommended in
      patients unable to tolerate standard first-line drug regimens or for isoniazid
      monoresistance. Evidence suggests that the standard 400-mg dose of moxifloxacin
      used in the treatment of tuberculosis may be suboptimal in some patients, leading
      to worse tuberculosis treatment outcomes and emergence of drug resistance.
      Furthermore, a drug interaction with the rifamycins results in up to 31% reduced
      plasma concentrations of moxifloxacin when these are combined for treatment of
      drug-susceptible tuberculosis, although the clinical relevance of this
      interaction is unclear. Moxifloxacin exhibits extensive interindividual
      pharmacokinetic variability. Higher doses of moxifloxacin may be needed to
      achieve drug exposures required for improved clinical outcomes. Further study is,
      however, needed to determine the safety of proposed higher doses and clinically
      validated targets for drug exposure to moxifloxacin associated with improved
      tuberculosis treatment outcomes. We discuss in this review the evidence for the
      use of moxifloxacin in drug-susceptible tuberculosis and explore the role of
      moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with
      rifamycins, on tuberculosis treatment outcomes when used in first-line
      tuberculosis drug regimens.

PMID- 28741302
TI  - Estimates of biologic variation in specific feline pancreatic lipase
      concentrations in cats without clinical or ultrasonographic evidence of
      pancreatitis.
AB  - BACKGROUND: Serum concentrations of feline-specific pancreatic lipase are
      commonly used for diagnosis and monitoring of pancreatitis in cats, but little is
      known regarding biologic variation of this analyte. OBJECTIVES: The purpose of
      the study was to determine biologic variation, index of individuality, and
      reference change values (RCV) for specific feline pancreatic lipase
      concentrations (Spec fPL) in apparently healthy cats. METHODS: Four blood samples
      were collected prospectively from 12 apparently healthy cats at 2-week intervals.
      The Spec fPL was measured in all serum samples by a reference laboratory.
      RESULTS: Intra-individual variation for Spec fPL was 33.5% (95% CI 27.1-43.8%);
      inter-individual variation was 99.9% (69.2-169.9%) and analytic variation was
      7.3% (6.1-9.2%). Reciprocal index of individuality for Spec fPL was 2.9 (2.5
      3.8), the 2-sided RCV was 95.1% (77.0-123.9%). CONCLUSIONS: Due to high
      individuality, use of a population-based RI for Spec fPL may fail to detect
      clinically significant elevations in individual cats. The use of subject-based
      RIs for Spec fPL may have greater sensitivity for the detection of a change in
      pancreatic physiology in cats; however, this would require serial assessment of
      apparently healthy cats.

PMID- 28741303
TI  - Open retropubic colposuspension for urinary incontinence in women.
AB  - BACKGROUND: Urinary incontinence is a common and potentially debilitating
      problem. Stress urinary, incontinence as the most common type of incontinence,
      imposes significant health and economic burdens on society and the women
      affected. Open retropubic colposuspension is a surgical treatment which involves
      lifting the tissues near the bladder neck and proximal urethra in the area behind
      the anterior pubic bones to correct deficient urethral closure to correct stress
      urinary incontinence. OBJECTIVES: The review aimed to determine the effects of
      open retropubic colposuspension for the treatment of urinary incontinence in
      women. A secondary aim was to assess the safety of open retropubic
      colposuspension in terms of adverse events caused by the procedure. SEARCH
      METHODS: We searched the Cochrane Incontinence Group Specialised Register, which
      contains trials identified from the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and
      handsearching of journals and conference proceedings (searched 5 May 2015), and
      the reference lists of relevant articles. We contacted investigators to locate
      extra studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled
      trials in women with symptoms or urodynamic diagnoses of stress or mixed urinary
      incontinence that included open retropubic colposuspension surgery in at least
      one trial group. DATA COLLECTION AND ANALYSIS: Studies were evaluated for
      methodological quality or susceptibility to bias and appropriateness for
      inclusion and data extracted by two of the review authors. Trial data were
      analysed by intervention. Where appropriate, a summary statistic was calculated.
      MAIN RESULTS: This review included 55 trials involving a total of 5417
      women.Overall cure rates were 68.9% to 88.0% for open retropubic colposuspension.
      Two small studies suggested lower incontinence rates after open retropubic
      colposuspension compared with conservative treatment. Similarly, one trial
      suggested lower incontinence rates after open retropubic colposuspension compared
      to anticholinergic treatment. Evidence from six trials showed a lower
      incontinence rate after open retropubic colposuspension than after anterior
      colporrhaphy. Such benefit was maintained over time (risk ratio (RR) for
      incontinence 0.46; 95% CI 0.30 to 0.72 before the first year, RR 0.37; 95% CI
      0.27 to 0.51 at one to five years, RR 0.49; 95% CI 0.32 to 0.75 in periods beyond
      five years).Evidence from 22 trials in comparison with suburethral slings
      (traditional slings or trans-vaginal tape or transobturator tape) found no
      overall significant difference in incontinence rates in all time periods
      evaluated (as assessed subjectively RR 0.90; 95% CI 0.69 to 1.18, within one year
      of treatment, RR 1.18; 95%CI 1.01 to 1.39 between one and five years, RR 1.11;
      95% CI 0.97 to 1.27 at five years and more, and as assessed objectively RR 1.24;
      95% CI 0.93 to 1.67 within one year of treatment, RR 1.12; 95% CI 0.82 to 1.54
      for one to five years follow up, RR 0.70; 95% CI 0.30 to 1.64 at more than five
      years). However, subgroup analysis of studies comparing traditional slings and
      open colposuspension showed better effectiveness with traditional slings in the
      medium and long term (RR 1.35; 95% CI 1.11 to 1.64 from one to five years follow
      up, RR 1.19; 95% CI 1.03 to 1.37).In comparison with needle suspension, there was
      a lower incontinence rate after colposuspension in the first year after surgery
      (RR 0.66; 95% CI 0.42 to 1.03), after the first year (RR 0.56; 95% CI 0.39 to
      0.81), and beyond five years (RR 0.32; 95% CI 15 to 0.71).Patient-reported
      incontinence rates at short, medium and long-term follow-up showed no significant
      differences between open and laparoscopic retropubic colposuspension, but with
      wide confidence intervals. In two trials incontinence was less common after the
      Burch (RR 0.38; 95% CI 0.18 to 0.76) than after the Marshall Marchetti Krantz
      procedure at one to five year follow-up. There were few data at any other follow
      up times.In general, the evidence available does not show a higher morbidity or
      complication rate with open retropubic colposuspension compared to the other open
      surgical techniques, although pelvic organ prolapse is more common than after
      anterior colporrhaphy and sling procedures. Voiding problems are also more common
      after sling procedures compared to open colposuspension. AUTHORS' CONCLUSIONS:
      Open retropubic colposuspension is an effective treatment modality for stress
      urinary incontinence especially in the long term. Within the first year of
      treatment, the overall continence rate is approximately 85% to 90%. After five
      years, approximately 70% of women can expect to be dry. Newer minimal access
      sling procedures look promising in comparison with open colposuspension but their
      long-term performance is limited and closer monitoring of their adverse event
      profile must be carried out. Open colposuspension is associated with a higher
      risk of pelvic organ prolapse compared to sling operations and anterior
      colporrhaphy, but with a lower risk of voiding dysfunction compared to
      traditional sling surgery. Laparoscopic colposuspension should allow speedier
      recovery but its relative safety and long-term effectiveness is not yet known. A
      Brief Economic Commentary (BEC) identified five studies suggesting that tension
      free vaginal tape (TVT) and laparoscopic colposuspension may be more cost
      effective compared with open retropubic colposuspension.

PMID- 28741304
TI  - Theranos Experience Exposes Weaknesses in FDA Regulatory Discretion.

PMID- 28741305
TI  - Erratum: Nguyen R, Jeha S, Zhou Y, et al. The Role of Leukapheresis in the
      Current Management of Hyperleukocytosis in Newly Diagnosed Childhood Acute
      Lymphoblastic Leukemia. Pediatr Blood Cancer. 2016;63:1546-1551.
      https://doi.org/10.1002/pbc.26056.

PMID- 28741306
TI  - New horizons on the landscape of AYA oncology.

PMID- 28741308
TI  - What is your diagnosis? Lymph node aspirates from a dog with prominent
      lymphadenomegaly.

PMID- 28741309
TI  - Interventional radiology in the management of the liver transplant patient.
AB  - Liver transplantation (LT) is commonly used to treat patients with end-stage
      liver disease. The evolution of surgical techniques, endovascular methods, and
      medical care has led to a progressive decrease in posttransplant morbidity and
      mortality. Despite these improvements, a multidisciplinary approach to each
      patient remains essential as the early diagnosis and treatment of the
      complications of transplantation influence graft and patient survival. The
      critical role of interventional radiology in the collaborative approach to the
      care of the LT patient will be reviewed. Liver Transplantation 23 1328-1341 2017
      AASLD.

PMID- 28741307
TI  - Modeling cost-effectiveness and health gains of a "universal" versus
      "prioritized" hepatitis C virus treatment policy in a real-life cohort.
AB  - : We evaluated the cost-effectiveness of two alternative direct-acting antiviral
      (DAA) treatment policies in a real-life cohort of hepatitis C virus-infected
      patients: policy 1, "universal," treat all patients, regardless of fibrosis
      stage; policy 2, treat only "prioritized" patients, delay treatment of the
      remaining patients until reaching stage F3. A liver disease progression Markov
      model, which used a lifetime horizon and health care system perspective, was
      applied to the PITER cohort (representative of Italian hepatitis C virus-infected
      patients in care). Specifically, 8,125 patients naive to DAA treatment, without
      clinical, sociodemographic, or insurance restrictions, were used to evaluate the
      policies' cost-effectiveness. The patients' age and fibrosis stage, assumed DAA
      treatment cost of ?15,000/patient, and the Italian liver disease costs were used
      to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness
      ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European
      scenario analysis was performed, resampling the study population, using the mean
      European country-specific health states costs and mean treatment cost of ?30,000.
      For the Italian base-case analysis, the cost-effective ICER obtained using policy
      1 was ?8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000
      probabilistic simulations. For the European treatment scenario the ICER obtained
      using policy 1 was ?19,541.75/QALY. ICER was sensitive to variations in DAA
      costs, in the utility value of patients in fibrosis stages F0-F3 post-sustained
      virological response, and in the transition probabilities from F0 to F3. The
      ICERs decrease with decreasing DAA prices, becoming cost-saving for the base
      price (?15,000) discounts of at least 75% applied in patients with F0-F2
      fibrosis. CONCLUSION: Extending hepatitis C virus treatment to patients in any
      fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness
      significantly increases when lowering treatment prices in early fibrosis stages.
      (Hepatology 2017;66:1814-1825).

PMID- 28741310
TI  - Homo- and heteropolymer self-assembly of recombinant trichocytic keratins.
AB  - In the past two decades, keratin biomaterials have shown impressive results as
      scaffolds for tissue engineering, wound healing, and nerve regeneration. In
      addition to its intrinsic biocompatibility, keratin interacts with specific cell
      receptors eliciting beneficial biochemical cues. However, during extraction from
      natural sources, such as hair and wool fibers, natural keratins are subject to
      extensive processing conditions that lead to formation of unwanted by-products.
      Additionally, natural keratins suffer from limited sequence tunability.
      Recombinant keratin proteins can overcome these drawbacks while maintaining the
      desired chemical and physical characteristics of natural keratins. Herein, we
      present the bacterial expression, purification, and solution characterization of
      human hair keratins K31 and K81. The obligate heterodimerization of the K31/K81
      pair that results in formation of intermediate filaments is maintained in the
      recombinant proteins. Surprisingly, we have for the first time observed new zero-
      and one-dimensional nanostructures from homooligomerization of K81 and K31,
      respectively. Further analysis of the self-assembly mechanism highlights the
      importance of disulfide crosslinking in keratin self-assembly.

PMID- 28741311
TI  - Some Methodologic Considerations in the Assessment of Methods for Predicting
      Pharmacokinetic Drug-Drug Interactions.

PMID- 28741312
TI  - Prediction of EPR Spectra of Lyotropic Liquid Crystals using a Combination of
      Molecular Dynamics Simulations and the Model-Free Approach.
AB  - We report the first application of fully atomistic molecular dynamics (MD)
      simulations to the prediction of the motional electron paramagnetic resonance
      (EPR) spectra of lyotropic liquid crystals in different aggregation states doped
      with a paramagnetic spin probe. The purpose of this study is twofold. First,
      given that EPR spectra are highly sensitive to the motions and order of the spin
      probes doped within lyotropic aggregates, simulation of EPR line shapes from the
      results of MD modelling provides an ultimate test bed for the force fields
      currently employed to model such systems. Second, the EPR line shapes are
      simulated using the motional parameters extracted from MD trajectories using the
      Model-Free (MF) approach. Thus a combined MD-EPR methodology allowed us to test
      directly the validity of the application of the MF approach to systems with multi
      component molecular motions. All-atom MD simulations using the General AMBER
      Force Field (GAFF) have been performed on sodium dodecyl sulfate (SDS) and
      dodecyltrimethylammonium chloride (DTAC) liquid crystals. The resulting MD
      trajectories were used to predict and interpret the EPR spectra of pre-micellar,
      micellar, rod and lamellar aggregates. The predicted EPR spectra demonstrate good
      agreement with most of experimental line shapes thus confirming the validity of
      both the force fields employed and the MF approach for the studied systems. At
      the same time simulation results confirm that GAFF tends to overestimate the
      packing and the order of the carbonyl chains of the surfactant molecules.

PMID- 28741314
TI  - The 2017 American Society for Preventive Cardiology Congress and Experts Course.

PMID- 28741313
TI  - Exploiting the MeDbz Linker To Generate Protected or Unprotected C-Terminally
      Modified Peptides.
AB  - C-terminally modified peptides are important targets for pharmaceutical and
      biochemical applications. Known methods for C-terminal diversification are
      limited mainly in terms of the scope of accessible modifications or by
      epimerization of the C-terminal amino acid. In this work, we present a broadly
      applicable approach that enables access to a variety of C-terminally
      functionalized peptides in either protected or unprotected form. This chemistry
      proceeds without epimerization of C-terminal Ala and tolerates nucleophiles of
      varying nucleophilicity. Finally, unprotected peptides bearing nucleophilic side
      chain groups can be selectively functionalized by strong nucleophiles, whereas
      macrocyclization is observed for weaker nucleophiles. The potential utility of
      this method is demonstrated through the divergent synthesis of the conotoxin
      conopressin G and GLP-1(7-36) and analogs.

PMID- 28741315
TI  - A mass spectrometry and DFT study of pyrithione complexes with transition metals
      in the gas phase.
AB  - 2-Mercaptopyridine N-oxide (pyrithione, PTOH) along with several transition metal
      ions forms coordination compounds displaying notable biological activities. Gas
      phase complexes formed between pyrithione and manganese (II), cobalt (II), nickel
      (II), copper (II), and zinc (II) were investigated by infusion in the
      electrospray source of a quadrupole-time of flight mass spectrometer. Remarkably,
      positive ion mode spectra displayed the singly charged metal adduct ion [C10 H8
      MN2 O2 S2 ]2+ ([M(PTO)2 ]+* or [M(DPTO)]+* ), where DPTO is dipyrithione, 2,2'
      dithiobis(pyridine N-oxide), among the most abundant peaks, implying a change in
      the oxidation state of whether the metal ion or the ligands. In addition, doubly
      charged ions were recognized as metal adduct ions containing DPTO ligands,
      [M(DPTO)n ]2+ . Generation of [M(PTO)2 ]+* / [M(DPTO)]+* could be traced by CID
      of [M(DPTO)2 ]2+ , by observation of the sequential losses of a charged (PTO+ )
      and a radical (PTO* ) deprotonated pyrithione ligand. The fragmentation pathways
      of [M(PTO)2 ]+* / [M(DPTO)]+* were compared among the different metal ions, and
      some common features were noticed. Density functional theory (DFT) calculations
      were employed to study the structures of the observed adduct ions, and
      especially, to decide in the adduct ion [M(PTO)2 ]+* / [M(DPTO)]+* whether the
      ligands are 2 deprotonated pyrithiones or a single dipyrithione as well as the
      oxidation state of the metal ion in the complex. Characterization of gas-phase
      pyrithione metal ion complexes becomes important, especially taking into account
      the presence of a redox-active ligand in the complexes, because redox state
      changes that produce new species can have a marked effect on the overall
      toxicological/biological response elicited by the metal system.

PMID- 28741317
TI  - Significantly Enhanced Hydrogen Evolution Activity of Freestanding Pd-Ru
      Distorted Icosahedral Clusters with less than 600 Atoms.
AB  - Freestanding metal nanoclusters can tune, precisely and effectively, the Gibbs
      free energy (DeltaGH ) of atomic hydrogen on the surface of materials. This
      enables the enhancement of hydrogen evolution activity. In this paper, we report
      a study of freestanding Pd-Ru distorted icosahedral clusters (ico-clusters) with
      less than 600 atoms by using a simple one-pot synthesis method. This Pd-Ru ico
      cluster can be used as an efficient electrocatalyst for the hydrogen evolution
      reaction (HER) in acidic water, which is a promising alternative to Pt. The
      experimental and theoretical results suggest that the face-centered cubic (fcc)
      freestanding Pd-Ru distorted ico-clusters with less than 600 atoms ensure
      increased active edges and distorted defect sites, which reduce the coordination
      number for the atoms on the catalyst surface. Furthermore, Ru is a more effective
      hydrogen dissociation source, whereas Pd has a better hydrogen storage function.
      Pd-Ru can tune the DeltaGH of atomic hydrogen adsorbed on a catalyst and reach an
      optimal equilibrium state that improves the HER performance. Our studies
      represent a robust approach towards the development of freestanding Pd-Ru
      distorted ico-clusters and advanced catalysts with non-Pt content for HER and
      many other heterogeneous reactions.

PMID- 28741316
TI  - Role of CD4 T cell helper subsets in immune response and deviation of CD8 T cells
      in mice.
AB  - The ability of different CD4+ T cell subsets to help CD8+ T-cell response is not
      fully understood. Here, we found using the murine system that Th17 cells induced
      by IL-1beta, unlike Th1, were not effective helpers for antiviral CD8 responses
      as measured by IFNgamma-producing cells or protection against virus infection.
      However, they skewed CD8 responses to a Tc17 phenotype. Thus, the apparent lack
      of help was actually immune deviation. This skewing depended on both IL-21 and IL
      23. To overcome this effect, we inhibited Th17 induction by blocking TGF-beta.
      Anti-TGF-beta allowed the IL-1beta adjuvant to enhance CD8+ T-cell responses
      without skewing the phenotype to Tc17, thereby providing an approach to harness
      the benefit of common IL-1-inducing adjuvants like alum without immune deviation.

PMID- 28741318
TI  - Protected Lithium-Metal Anodes in Batteries: From Liquid to Solid.
AB  - High-energy lithium-metal batteries are among the most promising candidates for
      next-generation energy storage systems. With a high specific capacity and a low
      reduction potential, the Li-metal anode has attracted extensive interest for
      decades. Dendritic Li formation, uncontrolled interfacial reactions, and huge
      volume effect are major hurdles to the commercial application of Li-metal anodes.
      Recent studies have shown that the performance and safety of Li-metal anodes can
      be significantly improved via organic electrolyte modification, Li-metal
      interface protection, Li-electrode framework design, separator coating, and so
      on. Superior to the liquid electrolytes, solid-state electrolytes are considered
      able to inhibit problematic Li dendrites and build safe solid Li-metal batteries.
      Inspired by the bright prospects of solid Li-metal batteries, increasing efforts
      have been devoted to overcoming the obstacles of solid Li-metal batteries, such
      as low ionic conductivity of the electrolyte and Li-electrolyte interfacial
      problems. Here, the approaches to protect Li-metal anodes from liquid batteries
      to solid-state batteries are outlined and analyzed in detail. Perspectives
      regarding the strategies for developing Li-metal anodes are discussed to
      facilitate the practical application of Li-metal batteries.

PMID- 28741319
TI  - Key genes of the sex pheromone biosynthesis pathway in female moths are required
      for pheromone quality and possibly mediate olfactory plasticity in conspecific
      male moths in Spodoptera litura.
AB  - Ninety sex pheromone biosynthesis genes in Spodoptera litura were identified in
      transcriptome data and were investigated and classified into the following five
      groups: fatty acid synthase, beta oxidase, fatty acyl-coenzyme A (CoA) reductase,
      desaturase and acetyl-CoA acetyltransferase. Fourteen female-specific genes were
      identified through semi-quantitative PCR, and 15 additional genes had expression
      levels that were 3- to 10-fold higher in females than in males. The majority of
      the genes had higher expression levels in the sex pheromone glands. Injection of
      double-stranded RNA (dsRNA) against nine selected genes showed that down
      regulation of Desaturase 3 (Des3), Des5 or fatty acyl coenzyme A reductase 17
      (FAR17) significantly changed the ratio of the four sex pheromone components
      (Z,E) -9,11-tetradecadienyl acetate (Z9E11-14:Ac), (Z,E)-9,12-Tetradecadienyl
      acetate(Z9E12-14:Ac), (Z)-9-tetradecenyl acetate (Z9-14:Ac), (E)-11-Tetradecenyl
      acetate(E11-14:Ac). These key genes were differentially expressed in female moths
      collected from different geographical regions. Furthermore, field bioassays
      demonstrated geographical variation in the olfactory profile of male moths in
      response to the different sex pheromone mixtures, which therefore indicates that
      a significant variation in the sex pheromone components exists in the natural
      population. Our results suggest that a change in the expression of these key
      genes, Des3, Des5 and FAR17, in the sex pheromone biosynthesis pathway could
      change the ratio of the sex pheromone components. We surmise that the
      differential expression levels of the key genes of the sex pheromone biosynthesis
      pathway may lead to differential ratios of the sex pheromones in the field. Our
      field trapping experiment suggested that the change of the ratio of the sex
      pheromone components may have been adapted by the olfactory system and possibly
      mediate olfactory plasticity in conspecific male moths.

PMID- 28741320
TI  - Differential intensity-dependent effects of pulsed electromagnetic fields on
      RANKL-induced osteoclast formation, apoptosis, and bone resorbing ability in
      RAW264.7 cells.
AB  - Pulsed electromagnetic fields (PEMF) have been proven to be effective for
      promoting bone mass and regulating bone turnover both experimentally and
      clinically. However, the exact mechanisms for the regulation of PEMF on
      osteoclastogenesis as well as optical exposure parameters of PEMF on inhibiting
      osteoclastic activities and functions remain unclear, representing significant
      limitations for extensive scientific application of PEMF in clinics. In this
      study, RAW264.7 cells incubated with RANKL were exposed to 15 Hz PEMF (2 h/day)
      at various intensities (0.5, 1, 2, and 3 mT) for 7 days. We demonstrate that bone
      resorbing capacity was significantly decreased by 0.5 mT PEMF mainly by
      inhibiting osteoclast formation and maturation, but enhanced at 3 mT by promoting
      osteoclast apoptosis. Moreover, gene expression of RANK, NFATc1, TRAP, CTSK, BAX,
      and BAX/BCL-2 was significantly decreased by 0.5 mT PEMF, but increased by 3 mT.
      Our findings reveal a significant intensity window for low-intensity PEMF in
      regulating bone resorption with diverse nature for modulating osteoclastogenesis
      and apoptosis. This study not only enriches our basic knowledge for the
      regulation of PEMF in osteoclastogenesis, but also may lead to more efficient and
      scientific clinical application of PEMF in regulating bone turnover and
      inhibiting osteopenia/osteoporosis. Bioelectromagnetics. 38:602-612, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28741321
TI  - [Articular fractures of the distal femur. Comparative analysis of three surgical
      treatments].
AB  - INTRODUCTION: The distal articular femur fracture is a serious injury that for
      years has been a problem in traumatology. It is often believed that produced
      varying degrees of permanent disability in the knee and that the fate of the
      joint was determined by the injury rather than treatment. OBJECTIVES: Present the
      results of surgical treatment of articular distal femur fractures type C2 with
      three treatment modalities: dynamic condylar screw (TDC), condylar buttress plate
      (PSC) and periarticular plate (PPA). MATERIAL AND METHODS: We conducted a
      comparative study of three therapeutic series designed to compare the
      effectiveness of dynamic condylar screw, the condylar buttress plate and
      periarticular plate in treating complete articular fractures of distal femur type
      C2. Patients of both genders, aged between 16 and 60 years, treated in the
      IAHULA, with a minimum follow up of 24 months. RESULTS: We included 42 patients
      divided into three groups. Males predominated with 73.8%, the most affected age
      group was 21-30 years with 28.57%. The most common type of fracture was the
      33C2.3 with 42.86%. The 71.43% of patients experienced complications,
      highlighting joint stiffness, angular deviation in recurvatum, chronic pain and
      post traumatic osteoarthritis. CONCLUSION: TDC and the PPA are valid options for
      the treatment of distal femur fractures AO 33C2, as offered better functional
      results than PSC.

PMID- 28741322
TI  - [Frecuency of diagnosis of bone lesions in cases of anterior glenohumeral
      dislocation].
AB  - BACKGROUND: Shoulder dislocation is a common reason for admission in the
      emergency room. Its recurrence rate may be as high as 96% due to the associated
      bone lesions. The purpose of this study is to identify the underreporting of
      lesions comparing those identified in the initial X-ray with those identified in
      the post-reduction X-ray. MATERIAL AND METHODS: X-rays of 46 patients with
      suspected anterior glenohumeral dislocation were assessed for diagnostic purposes
      and to identify the initial bone lesions. After patients had undergone reduction,
      post-reduction serial bone X-rays (AP, Stryker, Westpoint) were taken and
      analyzed looking for bone lesions that were initially missed. RESULTS: Bone
      lesions were identified in 26.1% of the patients based on the initial AP X-rays.
      In 67.6% of the patients without a pre-reduction fracture a bone lesion was found
      in the post-reduction serial X-rays. CONCLUSIONS: The underreporting rate of bone
      lesions was 67.6% comparing the initial AP X-rays with the post-reduction serial
      bone X-rays.

PMID- 28741323
TI  - [Osteosynthesis with locking plate and minimally invasive technique for proximal
      humeral fractures].
AB  - OBJECTIVE: To report our experience in the treatment of 2-3 fragment proximal
      humeral fractures using a minimally invasive technique that involves an angular
      stable locking implant and find out the factors affecting patients outcomes.
      MATERIAL AND METHODS: Descriptive, prospective study of the case series type.
      Twenty-two patients, 13 females and 9 males, were operated on between February
      2010 and August 2012. Mean age was 50.8 years (24-82 years). Patients were placed
      in a beach-chair position. A lateral acromial approach was used under
      fluoroscopic guidance. Minimal follow-up period was 24.3 months (11-32). Follow
      up consisted of X-ray review to check for bone healing and avascular necrosis,
      and functional assessment using the Constant-Murley scale. RESULTS: Bone healing
      occurred in all cases at 6 months. There were no cases of avascular necrosis. Two
      patients had varus healing (109o), and two had plate impingement. The functional
      assessment score according to the Constant-Murley scale was 68.8. There were no
      associated neurologic lesions. CONCLUSIONS: Fixation of proximal humeral
      fractures with a minimally invasive technique using locking plates represents a
      valid surgical approach. The avascular necrosis rate was low and early
      rehabilitation was possible in patients with poor bone quality.

PMID- 28741324
TI  - [Endoscopic treatment for the posterior impingement of the ankle].
AB  - BACKGROUND: Chronic pain on the posterior portion of the ankle is often due to
      posterior impingement between bony or soft tissue structures. The presence of an
      os trigonum or a prominent posterior apophysis of the talus can produce this
      impingement. The purpose of this study was to assess the outcome of hindfoot
      endoscopy in patients with a diagnosis of posterior ankle impingement. MATERIAL
      AND METHODS: We studied 24 individuals who underwent a posterior ankle endoscopic
      procedure during the period between 2008 and 2012, with the diagnosis of
      posterior ankle impingement. We analyzed variables such as: sport, level of
      sports activity according to the CLAS classification, return to sport. All
      patients were classified in accordance to the AOFAS and SFMCP (Societe Francaise
      de Medecine et Chirurgie du Pied) scores for ankle pathology. We measured patient
      satisfaction to the procedure with the Linkert scale. RESULTS: The average follow
      up was 27.13 +/- 5.26 months. The average age of our patients was 31.8 +/- 5.26
      years. We had 19 male (79.2%) and five female (20.8%) patients. The average
      preoperative Visual Analog Scale of pain (VAS) 5.75 and postoperative was 0.95.
      The average preoperative AOFAS scale of 76.22 +/- 5.29 rose to 97.21 +/- 1.96.
      The average preoperative SFCMP scale of 77.16 +/- 3.53 became 98.54 +/- 1.38. Our
      patients had their ankles immobilized for an average of 19.75 +/- 2.48 days. They
      returned to their sports activities at an average of 4.6 (+/- 1.27) months. Our
      patients rated their personal satisfaction as very satisfied in 16 cases (66.7%),
      satisfied in seven cases (29.2%), regular satisfaction in one case (4.2%). One
      patient developed a complex regional pain syndrome that was resolved with
      physical therapy and another had a wound erythema. CONCLUSION: The posterior
      ankle impingement is a pathology which diagnosis is mainly clinical, it is
      greatly associated with an os trigonum or a large Stieda process. It has a strong
      repercussion in the sports activities of the patients. The arthroscopic treatment
      is an ideal option for this pathology as it presents a good postoperative
      recovery with a swift return to patients preoperative sports activities.

PMID- 28741325
TI  - Continuous pain and swelling after humerus fracture in an 86-years-old woman.
AB  - Metastases to bone are the most frequent cause of destructive lesions to the
      skeleton in adults . The tumours that are most likely to metastasize to bone are
      prostate (32%), breast (22%), kidney (16%), lung and thyroid. The typical
      distribution of metastatic lesions are to the spine, ribs, pelvis, and proximal
      limb girdles. The humerus is the second most common site for long bone
      metastases, behind only the femur in its frequency of involvement . It represents
      the 20% of all bony metastases. We present a clinical case of an 86 yo woman with
      a previous diagnosis of myofibroblastic sarcoma of the maxillaris who suffers a
      pathological fracture of the humeral shaft secondary to metastasis and was
      misdiagnosed and treated for a typical humeral fracture using and intramedullary
      pinning (Hackethal technique), producing the progression of the disease within
      the humeral shaft. Due to the end state of the disease (multiple metastases), we
      decided to perform a palliative treatment with radiotherapy. This particular case
      report does confirm that is very important to rule out a malignancy in cases of
      osteolytic or poorly marginated lesions, particularly in patients older than 40
      years of age. Therefore, it is imperative that the treating physician has a
      rational and effective approach to the diagnostic evaluation and treatment of
      these patients in order to avoid a malpractice.

PMID- 28741326
TI  - [Dislocation of the proximal hallux interphalangeal joint with interposition of a
      sesamoid bone: a blibliographic review].
AB  - The irreducible dislocation of the hallux interphalangeal joint is an infrequent
      condition and only a few cases have been described. It presents as dorsal
      dislocation with interposition of the sesamoid bone, which has the possibility of
      being radiologically undetectable. We present the case of a 29 year-old patient
      who, after a sports trauma sustained a hallux interphalangeal dislocation that
      went unnoticed for eight days. Since, closed reduction was not possible, as
      occurred in several cases reported in the literature, open reduction was
      performed through a dorsal incision. Based on a bibliographic review, it is
      possible to state that there are several treatment options and multiple
      approaches, and that these lesions usually have a good prognosis.

PMID- 28741327
TI  - [Prescription pattern in the management of Type I open forearm fractures in
      pediatric patients].
AB  - BACKGROUND: Pediatric open fractures account for more tan 10% of hospital
      admissions in a Pediatric Trauma Clinical Department. It is important to identify
      the predominant surgical management prescription pattern in pediatric patients
      presenting with Type I open forearm fractures at a referral center in an emerging
      economy. MATERIAL AND METHODS: Observational, cross-sectional, analytical,
      secondary-source (logs) sampling study of consecutive cases. The cases included
      subjects under 17 years of age presenting with Type I open forearm fractures at a
      Pediatric Trauma Clinical Department from January 1st, 2009 to December 31st,
      2013. RESULTS: Ninety-two patients with a diagnosis of Type I open forearm
      fracture were included. All patients received parenteral antibiotics and
      underwent surgical debridement. However, in 69 (75%) of them a cast was used; in
      9 (10%) a splint was used; 9 (10%) underwent fixation with Kirschner nails, and 5
      (5.4%) underwent open reduction and internal fixation (ORIF). Eight patients (9%)
      required reoperation. CONCLUSIONS: Surgical management is the predominant
      prescription pattern in pediatric patients with Type I open forearm fracture. The
      latter is the predominant eepidemiology. The type of management was associated
      with a second surgery (p 0.000); however, this did not have a statistically
      significant impact on the hospital stay (p = 0.09).

PMID- 28741328
TI  - [Short-term results of Weils osteotomy in patients with propulsive
      metatarsalgia].
AB  - INTRODUCTION: Metatarsalgia is the most common reason for consultation in
      orthopedic pathology of the foot. The key to its treatment lies in the correct
      determination of the symptoms, which are biological, morphological and mechanical
      alterations responsible for pain. Weil's osteotomy is commonly used for multiple
      forefoot pathologies, including metatarsalgias. MATERIAL AND METHODS: We included
      patients with first-line failure syndrome and associated mechanical metatarsalgia
      producing deformities. The minimum follow-up was six months. All individuals were
      interviewed with a standardized questionnaire based on the AOFAS, a survey to
      know their degree of satisfaction about the surgery. RESULTS: Twelve female
      subjects with a mean age of 51 years were recruited between March and September
      of 2013. Seven right feet, five left. The AOFAS values improved only in six, in
      which an excellent result was obtained; five rated them as good and six as
      unsatisfactory. CONCLUSIONS: In a very small series, postoperative complications
      were observed when the shortening of the metatarsal was greater than four
      millimeters, with the appearance of stiffness (floating finger).

PMID- 28741329
TI  - [Localized pigmented vellonodular sunovitis, cause of knee hemarthrosis].
AB  - The pigmented vellonodular sinovitis (PVNS) is benign neoplasm with synovial
      proliferation and hemosiderin deposit, characterized by large compromising
      joints, especially the knee. At present, two variants of clinics, the diffuse
      form (PVNSD) and the localized (PVNSL) are described. Arthroscopic synovectomy
      and radiosynoviorthesis (RSO) is the treatment that has shown the best functional
      results. Nuclear magnetic resonance is an appropriate method for conducting the
      diagnosis of PVNSL.

PMID- 28741330
TI  - World hepatitis day. Fighting hepatitis C in Latin America and the Caribbean; an
      urgent call.

PMID- 28741331
TI  - Alignment of adherence and risk for HIV acquisition in a demonstration project of
      pre-exposure prophylaxis among HIV serodiscordant couples in Kenya and Uganda: a
      prospective analysis of prevention-effective adherence.
AB  - INTRODUCTION: Adherence is essential for pre-exposure prophylaxis (PrEP) to
      protect against HIV acquisition, but PrEP use need not be life-long. PrEP is most
      efficient when its use is aligned with periods of risk - a concept termed
      prevention-effective adherence. The objective of this paper is to describe
      prevention-effective adherence and predictors of adherence within an open-label
      delivery project of integrated PrEP and antiretroviral therapy (ART) among HIV
      serodiscordant couples in Kenya and Uganda (the Partners Demonstration Project).
      METHODS: We offered PrEP to HIV-uninfected participants until the partner living
      with HIV had taken ART for >=6 months (a strategy known as "PrEP as a bridge to
      ART"). The level of adherence sufficient to protect against HIV was estimated in
      two ways: >=4 and >=6 doses/week (per electronic monitoring). Risk for HIV
      acquisition was considered high if the couple reported sex with <100% condom use
      before six months of ART, low if they reported sex but had 100% condom use and/or
      six months of ART and very low if no sex was reported. We assessed prevention
      effective adherence by cross-tabulating PrEP use with HIV risk and used
      multivariable regression models to assess predictors of >=4 and >=6 doses/week.
      Results A total of 985 HIV-uninfected participants initiated PrEP; 67% were male,
      median age was twenty-nine years, and 67% reported condomless sex in the month
      before enrolment. An average of >=4 doses and >=6 doses/week were taken in 81%
      and 67% of participant-visits, respectively. Adherence sufficient to protect
      against HIV acquisition was achieved in 75-88% of participant-visits with high
      HIV risk. The strongest predictor of achieving sufficient adherence was reporting
      sex with the study partner who was living with HIV; other statistically
      significant predictors included no concerns about daily PrEP, pregnancy or
      pregnancy intention, females aged >25 years, older male partners and desire for
      relationship success. Predictors of not achieving sufficient adherence were no
      longer being a couple, delayed PrEP initiation, >6 months  of follow-up, ART use
      >6 months  by the partner living with HIV and problem alcohol use. CONCLUSIONS:
      Over three-quarters of participant-visits by HIV-uninfected partners in
      serodiscordant couples achieved prevention-effective adherence with PrEP. Greater
      adherence was observed during months with HIV risk and the strongest predictor of
      achieving sufficient adherence was sexual activity.

PMID- 28741332
TI  - Willingness to use HIV pre-exposure prophylaxis among gay men, other men who have
      sex with men and transgender women in Myanmar.
AB  - INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) has emerged as a key component
      of contemporary HIV combination prevention strategies. To explore the local
      suitability of PrEP, country-specific acceptability studies are needed to inform
      potential PrEP implementation. In the context of Myanmar, in addition to resource
      constraints, HIV service access by gay men, other men who have sex with men, and
      transgender women (GMT) continues to be constrained by legislative and community
      stigma and marginalization. We aimed to determine PrEP acceptability among GMT in
      Myanmar and explore the factors associated with willingness to use PrEP. METHODS:
      GMT were recruited in Yangon and Mandalay through local HIV prevention outreach
      programmes in November and December 2014. Quantitative surveys were administered
      by trained peer educators and collected data on demographics, sexual risk,
      testing history and PrEP acceptability. A modified six-item PrEP acceptability
      scale classified self-reported HIV undiagnosed GMT as willing to use PrEP.
      Multivariable logistic regression identified factors associated with willingness
      to use PrEP. RESULTS: Among 434 HIV undiagnosed GMT, PrEP awareness was low (5%).
      PrEP acceptability was high, with 270 (62%) GMT classified as willing to use
      PrEP. GMT recruited in Mandalay (adjusted odds ratio (aOR) = 1.79; 95%CI = 1.05
      3.03), who perceived themselves as likely to become HIV positive (aOR = 1.82;
      95%CI = 1.10-3.02), who had more than one recent regular partner (aOR = 2.94;
      95%CI = 1.41-6.14), no regular partners (aOR = 2.05; 95%CI = 1.10-3.67), more
      than five casual partners (aOR = 2.05; 95%CI = 1.06-3.99) or no casual partners
      (aOR = 2.25; 95%CI = 1.23-4.11) were more likely to be willing to use PrEP. The
      association between never or only occasionally using condoms with casual partners
      and willingness to use PrEP was marginally significant (aOR = 2.02; 95%CI = 1.00
      4.10). GMT who reported concern about side effects and long-term use of PrEP were
      less likely (aOR = 0.35; 95%CI = 0.21-0.59) to be willing to use PrEP.
      CONCLUSIONS: This is the first study to assess PrEP acceptability in Myanmar.
      Findings suggest PrEP is an acceptable prevention option among GMT in Myanmar,
      providing they are not required to pay for it. Implementation/demonstration
      projects are needed to explore the feasibility and cost-effectiveness of PrEP as
      a prevention option for GMT in Myanmar.

PMID- 28741333
TI  - HIV-affected couples and individuals who desire children should be offered
      options for safer conception.

PMID- 28741334
TI  - Endovascular treatment of chronic occluded popliteal artery aneurysm: early and
      mid-term outcomes.
AB  - BACKGROUND: Critical limb ischemia (CLI) may be the consequence of chronic
      occluded popliteal artery aneurysm (PAA). Open repair (OR) offers better 5-year
      results than endovascular treatment, but in patients with severe comorbidities or
      unfit to OR, endovascular repair (ER) could represent a valid treatment option.
      The purpose of this retrospective study was to review our experience of
      endovascular popliteal aneurism repair (EVPAR) in patients with chronic occluded
      PAA. METHODS: The endpoints assessed were: 1- and 3-year primary and secondary
      patency rates, technical success, 30-day major adverse events, major amputation
      free-survival, re-intervention and survival rates. RESULTS: From May 2011 to
      April 2015, 25 patients (23 male), mean age of 74.4 years, underwent an EVPAR. No
      perioperative death and vascular access complications were recorded. Device
      technical success rate was 100%. The 30-day major adverse events rate was 4%: one
      stent graft occlusion with distal embolization was recorded. The 1- and 3-year
      primary and secondary patency rate were 79% and 85.8%, and 73.3% and 79.7%,
      respectively. At 3-year follow-up, the freedom from major amputation and survival
      rates were 100% and 96%. Stent-graft coverage length >20 cm (P=0.006), more than
      2 stents used (P=0.005), and poor distal runoff (P=0.01) were negative predictors
      for patency. CONCLUSIONS: The results of this retrospective study suggest that
      EVPAR seems a safe and efficacious treatment option in selected patients. Despite
      encouraging results, further research will be needed to assess long-terms results
      and to define the best treatment option for patient with chronic occluded PAA.

PMID- 28741335
TI  - Cardiopulmonary bypass time: every minute counts.
AB  - BACKGROUND: This study was conducted to examine the impact of CPB times on
      postoperative outcomes. We sought to determine the optimum cut-offs of CPB per
      graft time and cumulative CPB time and their predictive accuracy for mortality in
      conjunction with EuroSCORE II. METHODS: The de-identified data of 1960 patients
      who had undergone isolated on-pump CABG from 2009 to 2014 were analyzed. The risk
      strata of cardiopulmonary bypass (CPB)/graft and cumulative CPB times, identified
      with a decision tree, were added into an augmented model for predicting short-
      and intermediate-term postoperative clinical events. RESULTS: Prolonged
      cumulative CPB time (>180 minutes) was significant in predicting mortality while
      adjusting for EuroSCORE II, postoperative complications, prolonged ICU stay and
      prolonged mechanical ventilation. Whereas prolonged CPB/graft time (>56 minutes)
      was marginally non-significant in terms of its direct effects, its indirect
      effect on mortality could be manifested through enhanced risks of complications,
      prolonged ICU stay (>48 hours) and prolonged mechanical ventilation (>24 hours).
      CONCLUSIONS: Prolonged CPB times could predict postoperative clinical events, in
      particular mortality. To minimize the occurrence of unfavorable adverse outcomes,
      it is recommended that the CPB/graft time and cumulative CPB time be kept below
      56 minutes and 180 minutes respectively.

PMID- 28741336
TI  - Single-centre early experience with sutureless valve Perceval: focus onto size
      gaining.

PMID- 28741337
TI  - Spinturnix dasycnemi (Acari: Spinturnicidae) - a poorly known Palaearctic bat
      mite: first records in Poland and morphometric separation from two other species
      of the myoti group
AB  - Spinturnix dasycnemi (Kolenati, 1856), an ectoparasite considered to be specific
      to rare and local bat species Myotis dasycneme (Boie, 1825), is reported for the
      first time in the fauna of Poland. Specimens were collected from M. dasycneme at
      two localities in the north and central parts of the country. In Europe, only two
      males of that poorly known mite species have been recorded recently from the
      Netherlands and Slovakia, while spinturnicids from pond bats were identified as
      S. andegavina and/or S. myoti in most of previous studies. The exact geographic
      distribution of S. dasycnemi is unknown, mainly due to the possibility of its
      common confusion with other mite species, but it may occur in all countries
      hosting populations of M. dasycneme. We show that specimens of both sexes of S.
      dasycnemi are morphometrically clearly separable from those of S. myoti and S.
      andegavina, even based on a combination of idiosoma length and dorsal shield
      length.

PMID- 28741338
TI  - Fungi of the genus Rhodotorula isolated from the oral cavity of oncologic
      patients with colorectal cancer
AB  - This paper concerns the frequency of occurrence and enzymatic activity of fungi
      of the genus Rhodotorula isolated from the oral cavity of patients with
      colorectal cancer. Swabs from the oral cavity were subjected to standard
      mycological diagnostic procedures; enzymatic activity of the fungi was evaluated
      using and API Zym test by BioMereux. The fungi of the genus Rhodotorula were
      noted in 22.5% positive isolates originating from women and 25.7% positive
      isolates originating from men. They included mono-species isolates of: Rh.
      glutinis, Rh. minuta, Rh. mucilaginosa and two-species isolates: Rh. minuta +
      Candida dubliniensis, Rh. mucilaginosa + C. albicans and Rh. mucilaginosa +
      Saccharomyces cerevisiae. The enzymatic activity of the isolated fungi was
      evaluated as high and veryhigh in the case of acidic and alkaline phosphatase,
      esterase lipase, lipase, as well as leucine, valine and cysteine arylamidase. The
      highest values were determined in Rh. mucilaginosa with co-occurrence of C.
      albicans and Rh. minuta with co-occurrence of C. dubliniensis. In the ontosphere
      of oncologic patients, the increasingly frequent appearance of the species of
      fungi with high and very high enzymatic activity indicates the progressing risk
      posed by opportunisticforms, which includes Rhodotorula species.

PMID- 28741339
TI  - The enzymes and electrolytes profiles in sera of Iranian stray dogs naturally
      infected with Neospora caninum
AB  - The protozoan Neospora caninum (Apicomplexa: Sarcocystidae), respectively infects
      canids and ruminants as the most definitive and intermediate hosts. A diagnosis
      of neosporosis is generally made on the basis of clinical signs together with the
      detection of high levels of antibodies in serum. The present study compares the
      serum electrolyte profile (Ca, K, Mg, Na, P) and serum enzyme level (ALP, AST,
      CPK) of non-infected dogs with those of stray dogs naturally infected with N.
      caninum. The indirect fluorescent antibody test (IFAT) revealed that 17 of the
      137 analysed serum samples (12.41%) of the stray dogs were seropositive (Sp) to
      N. caninum. Serum levels of the electrolytes and the enzymes were evaluated in
      the 17 Sp and 28 seronegative (Sn, 20.44%) dogs using common enzymekits,
      spectrophotometry and flame photometry techniques. The average serum level of
      ALP, AST, and CPK were found to be significantly higher in the Sp stray dogs.
      Measurements of the average serum levels of Ca, K, Mg, and P were higher in Sp
      than Sn stray dogs, with the average K level being significantly higher in
      seropositive stray dogs. It was concluded that evaluation of serum enzyme and
      electrolyte levels may be used to screen N. caninum infection in straydogs.

PMID- 28741340
TI  - A human case of urogenital myiasis caused by Psychoda sp. larvae in Tripoli,
      Libya
AB  - Urogenital myiasis caused by Psychoda spp. involving human are very rare and
      present with unusual symptoms. Larvae belonging to Psychoda sp. (Diptera:
      Psychodidae) were found in the urogenital tract of a 9-year-old girl, who lives
      in Tajoura, Libya, and had suffered from genital pruritus and moving larvae in
      urine. This is the first record of such case in Libya.

PMID- 28741341
TI  - Comments on article "Molecular characterization and phylogenetic analysis of
      Microsporidia and Cryptosporidium spp. in patients with multiple bowel biopsies
      from Fars Province, Iran"

PMID- 28741342
TI  - Hygiene pests as vectors for parasitic and bacterial diseases in humans
AB  - Diseases transmitted by hygiene pests remain a very serious problem in spite of
      fast developments in science and medicine. The present study focuses on pests
      carrying germs that pose a threat to human health and life. The quick pace of
      life, the need to satisfy human needs and mass production of food sometimes
      result in flagrant sanitary, hygienic and epidemiological deficiencies. These
      irregularities are conducive to hygiene pests, which, when not held in check by
      proper control measures, may act more efficiently and quickly.

PMID- 28741343
TI  - Relationships between certain metabolic diseases and selected serum biochemical
      parameters in seropositive dairy cows against Neospora caninum infection in
      different stages of lactation
AB  - Neospora caninum is an important cause of abortion in dairy cattle. The general
      health of affected cows has not been investigated before. Therefore, the main
      objective of this study was to identify possible relationships between certain
      metabolic diseases and selected serum biochemical parameters in seropositive
      dairy cows against N. caninum antibodies in different stages of lactation. The
      study was carried out using 72 N. caninum seropositive cows and 61 seronegative
      dairy cows (control). Serum from all cows was tested to determine their N.
      caninum status (seropositive vs seronegative) using commercially available
      indirect enzyme-linked immunosorbent assay test kit (iELISA). In addition, serum
      biochemical parameters including beta-hydroxybutyrate (BHB), glucose, creatinine,
      blood urea nitrogen, total protein, albumin, alkaline phosphatase (ALP),
      aspartate aminotransferase (AST), alanine transaminase (ALT), lactate
      dehydrogenase (LDH) and gamma-glutamyltranspeptidase (GGT) were determined using
      routine laboratory methods. The stage of lactation was obtained at the time of
      sampling from farm records. Student independent t-test showed that there was a
      significant difference in the serum concentrations of BHB, AST, ALT, and LDH
      between seropositive and seronegative cows. There was no significant association
      between seropositivity and the stage of lactation. However, multivariable
      logistic regression analysis showed that there was a strong association between
      seropositivity and BHB concentrations. Results of this study indicate a possible
      relationship between N. caninum seropositivity and certain metabolic diseases
      such as ketosis and fatty liver syndrome in dairy cows.

PMID- 28741344
TI  - Anidulafungin in children: Experience in a tertiary care children's hospital in
      Argentina.
AB  - The experience using anidulafungin for the treatment of invasive fungal
      infections in pediatrics is limited. In this article, we describe our experience
      in 55 children. Anidulafungin was administered intravenously at a loading dose of
      3 mg/kg once daily, followed by 1.5 mg/kg every 24 hours over a mean period of 14
      days (range: 7-22 days). Patients' median age was 114 months old (interquartile
      range: 32-168 months old). All patients had underlying diseases. Among patients
      with bone marrow transplant, the difference in white blood cell count,
      transaminase levels, and renal function at baseline and at the end of
      anidulafungin administration was not significant. No adverse events were reported
      and no patient died from an anidulafungin-related cause. Anidulafungin may be
      considered an alternative for the prophylaxis or treatment of invasive fungal
      infections in pediatrics but methodologically robust studies are needed to
      confirm this.

PMID- 28741345
TI  - Direct Detection of Nucleic Acid with Minimizing Background and Improving
      Sensitivity Based on a Conformation-Discriminating Indicator.
AB  - As is well-known, the nucleic acid indicator-based strategy is one of the major
      approaches to monitor the nucleic acid hybridization-mediated recognition events
      in biochemical analysis, displaying obvious advantages including simplicity, low
      cost, convenience, and generality. However, conventional indicators either hold
      strong self-fluorescence or can be lighted by both ssDNA and dsDNA, lacking
      absolute selectivity for a certain conformation, always with high background
      interference and low sensitivity in sensing; and additional processing (e.g.,
      nanomaterial-mediated background suppression, and enzyme-catalyzed signal
      amplification) is generally required to improve the detection performance. In
      this work, a carbazole derivative, EBCB, has been synthesized and screened as a
      dsDNA-specific fluorescent indicator. Compared with conventional indicators under
      the same conditions, EBCB displayed a much higher selective coefficient for
      dsDNA, with little self-fluorescence and negligible effect from ssDNA. Based on
      its superior capability in DNA conformation-discrimination, high sensitivity with
      minimizing background interference was demonstrated for direct detection of
      nucleic acid, and monitoring nucleic acid-based circuitry with good reversibity,
      resulting in low detection limit and high capability for discriminating base
      mismatching. Thus, we expect that this highly specific DNA conformation
      discriminating indicator will hold good potential for application in biochemical
      sensing and molecular logic switching.

PMID- 28741346
TI  - Occurrence State and Molecular Structure Analysis of Extracellular Proteins with
      Implications on the Dewaterability of Waste-Activated Sludge.
AB  - The occurrence state and molecular structure of extracellular proteins were
      analyzed to reveal the influencing factors on the water-holding capacities of
      protein-like substances in waste-activated sludge (WAS). The gelation process of
      extracellular proteins verified that advanced oxidation processes (AOPs) for WAS
      dewaterability improvement eliminated the water affinity of extracellular
      proteins and prevented these macromolecules from forming stable colloidal
      aggregates. Isobaric tags for relative and absolute quantitation proteomics
      identified that most of the extracellular proteins were originally derived from
      the intracellular part and the proteins originally located in the extracellular
      part were mainly membrane-associated. The main mechanism of extracellular protein
      transformation during AOPs could be represented by the damage of the membrane or
      related external encapsulating structure and the release of intracellular
      substances. For the selected representative extracellular proteins, the strong
      correlation (R2 > 0.97, p < 0.03) between the surface hydrophilicity index and
      alpha-helix percentages in the secondary structure indicated that the water
      affinity relied more on the spatial distribution of hydrophilic functional groups
      rather than the content. Destructing the secondary structure represented by the
      alpha-helix and stretching the polypeptide aggregation in the water phase through
      disulfide bond removal might be the key to eliminating the inhibitory effects of
      extracellular proteins on the interstitial water removal from WAS.

PMID- 28741347
TI  - A Probe for the Detection of Hypoxic Cancer Cells.
AB  - Hypoxia is a common feature of tumor cells. Nitroreductase (NTR), a common
      biomarker of hypoxia, has been widely used to evaluate the extent of tumor
      hypoxia. In this study, three fluorescent probes (FBN-1-3) were synthesized to
      monitor the extent of hypoxia in cancer cells in real time. FBN-1-3 were composed
      of a fluorescein analogue and one of three different aromatic nitro groups. Of
      these probes, FBN-1 showed excellent sensitivity and selectivity in detecting
      hypoxia via a reduction in O2 concentration. Confocal fluorescence imaging and
      flow cytometry demonstrated that HepG-2, A549, and SKOV-3 cells incubated with
      FBN-1 under reduced oxygen conditions showed significantly enhanced fluorescence.
      A mouse HepG-2 tumor model confirmed that FBN-1 responds rapidly to NTR and can
      be used to evaluate the degree of tumor hypoxia. The changes in intra- and
      extracellular NTR in tumor cells were also concurrently monitored, which did not
      reveal a link between NTR concentration and degree of hypoxia. Our work provides
      a functional probe for tumor hypoxia, and our results suggest the fluorescent
      response of our probe is due to a decrease in O2 concentration, and not NTR
      concentration.

PMID- 28741348
TI  - Super-Resolution Far-Field Infrared Imaging by Photothermal Heterodyne Imaging.
AB  - Infrared (IR) imaging provides chemical-specific information without the need for
      exogenous labels. Conventional far-field IR imaging techniques are diffraction
      limited, which means an effective spatial resolution of >5 MUm with currently
      available optics. In this article, we present a novel far-field IR imaging
      technique based on photothermal heterodyne imaging (IR-PHI). In our version of IR
      PHI, an IR pump laser excites the sample, causing a small temperature rise that
      is detected by a counterpropagating visible probe beam. Images and spectra of
      several different types of soft matter systems (polystyrene beads, thin polymer
      films, and single Escherichia coli bacterial cells) are presented to demonstrate
      the sensitivity and versatility of the technique. Importantly, the spatial
      resolution in the IR-PHI measurements is determined by the visible probe beam: a
      spatial resolution of 0.3 MUm was achieved with a 0.53 MUm probe wavelength and a
      high numerical aperture focusing objective. This is the highest spatial
      resolution reported to date for far-field IR imaging. Analysis of the experiments
      shows that for polymer beads in a dry environment, the magnitude of the IR-PHI
      signal is determined by the scattering cross section of the nano-object at the
      probe wavelength. This is in contrast to conventional PHI experiments in a heat
      transfer medium, where the signal scales as the absorption cross section. This
      different scaling can be understood through the optical theorem. Our analysis
      also shows that both thermal expansion and changes in the refractive index of the
      material are important and that these two effects, in general, counteract each
      other.

PMID- 28741349
TI  - Interface Effects on the Ion Transport of Epitaxial Y2Zr2O7 Films.
AB  - The systematic study of the ionic transport properties of epitaxial Y2Zr2O7 films
      with defective fluorite structure reveals an enhanced oxygen vacancy conductivity
      at the interface between the films and the MgO(110) substrate, which is
      characterized by a high density of misfit dislocations. This beneficial effect is
      discussed in terms of space-charge and mobility effects.

PMID- 28741350
TI  - 3D Printed and Microcontrolled: The One Hundred Dollars Scanning Electrochemical
      Microscope.
AB  - The design and fabrication of a versatile and low-cost electrochemical-scanning
      probe microscope (EC-SPM) is presented. The proposed equipment relies on the use
      of modern prototyping tools such as 3D printers and microcontroller boards and
      only a few "off-the-shelf" parts to deliver a simple yet powerful EC-SPM
      equipment capable of performing simple space-resolved electrochemical
      measurements. The equipment was able to perform space-resolved electrochemical
      measurements using a platinum ultramicroelectrode (UME) as the working electrode
      on a scanning electrochemical microscopy (SECM) configuration and was used to
      record approach curves, line scans, and array scans over an insulating substrate.
      The performance of the proposed equipment was found to be adequate for simple
      SECM measurements under hindered diffusion conditions. Because of its flexible
      design (software and hardware), more complex array scan patterns, only found on
      high-end EC-SPM setups such as hopping mode scan, were easily implemented on the
      built equipment. Despite its simplicity, the versatility and low cost of the
      proposed design make it an attractive alternative as a teaching platform as well
      as a platform for developing more elaborate EC-SPM setups.

PMID- 28741351
TI  - Ultralight Interconnected Graphene-Amorphous Carbon Hierarchical Foam with
      Mechanical Resiliency for High Sensitivity and Durable Strain Sensors.
AB  - Ultralight graphene-amorphous carbon (AC) hierarchical foam (G-ACHF) was
      synthesized by chemical vapor deposition at 1065  degrees C, close to the melting
      point of copper. The high temperature leads to the hierarchical structure with an
      inner layer of graphene and an outer layer of AC. The inner graphene layer with
      high conductivity and integrity provides high sensitivity. The outer AC layer
      helps to enhance its durability and mechanical resiliency. The hierarchical
      structure recovers without damaging the structural integrity after a large strain
      of 90%. The electrical resistance of G-ACHF remains stable after 200 cycles of
      compression to a strain level of 50%. The fluctuation of the resistance value
      remains within +/-3%, showing its stability in sensing performance. The pressure
      sensitivity of G-ACHF reaches as high as ~11.47 Pa-1. Finite element simulation
      reveals that the stress borne by the key position of G-ACHF is 47% lower than
      that of graphene foam without the AC layer, proving that the AC layer can
      disperse the stress effectively. With a very low density of 1.17 * 10-3 g cm-1,
      the reversibly compressible G-ACHF strain sensor material exhibits its promising
      application potential in lightweight and wearable devices.

PMID- 28741352
TI  - Unified Synthesis of Right Halves of Halichondrins A-C.
AB  - The right halves of halichondrins A-C were synthesized by coupling the common C20
      C37 building block 9 with the C1-C19 building blocks 10a-c, respectively.
      Catalytic, asymmetric Ni/Cr-mediated coupling was used for three C-C bond
      formations. For all cases, the stereochemistry was controlled with the Cr
      catalyst prepared from the chiral sulfonamide identified via the toolbox
      approach. For (3 + 4)-, (6 + 7)-, and (9 + 10)-couplings, the stereoselectivity
      of 28:1, >40:1, and ~20:1 was achieved by the Cr catalysts prepared from (S)-H,
      (S)-I, and (R)-L, respectively. Unlike the first and second couplings, the third
      coupling used the structurally complex nucleophile. It was demonstrated that the
      coupling efficiency was excellent even with the electrophile/nucleophile molar
      ratio = 1.0/1.1. In addition, the third coupling was achieved with the substrate
      bearing a free hydroxyl group. The products obtained in the Ni/Cr-mediated
      couplings were converted to the right halves of halichondrins A-C in excellent
      overall yields. The right halves of halichondrins A-C (1a-c) were synthesized in
      28, 24, and 24 steps from commercial d-galactal in 13.4%, 21.1%, and 16.7%
      overall yield, respectively.

PMID- 28741353
TI  - Efficient Heterostructures of Ag@CuO/BaTiO3 for Low-Temperature CO2 Gas
      Detection: Assessing the Role of Nanointerfaces during Sensing by Operando DRIFTS
      Technique.
AB  - Tetragonal BaTiO3 spheroids synthesized by a facile hydrothermal route using
      Tween 80 were observed to be polydispersed with a diameter in the range of ~15-75
      nm. Thereon, BaTiO3 spheroids were decorated with different percentages of Ag@CuO
      by wet impregnation, and their affinity toward carbon dioxide (CO2) gas when
      employed as sensitive layers in a microsensor was investigated. The results
      revealed that the metal nanocomposite-based sensor had an exceptional stability
      and sensitivity toward CO2 gas (6-fold higher response), with appreciable
      response and recovery times (<10 s) and higher repeatability (98%) and accuracy
      (96%) at a low operating temperature of 120  degrees C, compared to those of pure
      BaTiO3 and CuO. Such improved gas-sensing performances even at a very low
      concentration (~700 ppm) is attributable to both the chemical and electrical
      contributions of Ag@CuO forming intermittent nanointerfaces with BaTiO3
      spheroids, exhibiting unique structural stability. The CO2-sensing mechanism of
      CuO/BaTiO3 nanocomposite was studied by the diffuse reflectance infrared Fourier
      transform spectroscopy technique that established the reaction of CO2 with BaO
      and CuO to form the respective carbonate species that is correlated with the
      change in material resistance consequently monitored as sensor response.

PMID- 28741354
TI  - Stereocontrolled Synthesis of Left Halves of Halichondrins.
AB  - A stereocontrolled synthesis of the left halves of halichondrins was reported. An
      intramolecular oxy-Michael reaction under basic conditions was used to construct
      the [6,6]-spiroketal in a stereocontrolled manner. With this approach, the left
      halves of halichondrins, homohalichondrins, and norhalichondrins were
      synthesized.

PMID- 28741355
TI  - Pt Nanoparticles Densely Coated on SnO2-Covered Multiwalled Carbon Nanotubes with
      Excellent Electrocatalytic Activity and Stability for Methanol Oxidation.
AB  - A new electrocatalyst exhibiting enhanced activity and stability is designed from
      SnO2-covered multiwalled carbon nanotubes coated with 85 wt % ratio Pt
      nanoparticles (NPs). This catalyst showed a mass activity 6.2 times as active as
      that of the commercial Pt/C for methanol oxidation, owing to the unique one
      dimensional structure. Moreover, the durability and antipoisoning ability were
      also improved greatly. The enhanced intrinsic performance was ascribed to the
      densely connected networks of Pt NPs on the SnO2 NPs.

PMID- 28741356
TI  - Solvent-Selective Reactions of Alkyl Iodide with Sodium Azide for Radical
      Generation and Azide Substitution and Their Application to One-Pot Synthesis of
      Chain-End-Functionalized Polymers.
AB  - Herein, a new reaction of an alkyl iodide (R-I) with an azide anion (N3-) to
      reversibly generate the corresponding alkyl radical (R*) is reported. Via this
      new reaction, N3- was used as an efficient catalyst in living radical
      polymerization, yielding a well-defined polymer-iodide. A particularly
      interesting finding was the solvent selectivity of this reaction; namely, R-I and
      N3- generated R* in nonpolar solvents, while the substitution product R-N3 was
      generated in polar solvents. Exploiting this unique solvent selectivity, a one
      pot synthesis of polymer-N3 was attained. N3- was first used as a catalyst for
      living radical polymerization in a nonpolar solvent to produce a polymer-iodide
      and was subsequently used as a substitution agent in a polar solvent by simply
      adding the polar solvent, thereby transforming the polymer-iodide to polymer-N3
      in one pot. This one-pot synthesis was further applied to obtain N3-chain-end
      functionalized polymer brushes on the surface, uniquely controlling the N3
      coverage (number density). Using the chain-end N3, the obtained linear and brush
      polymers were connected to functional molecules via an azide-alkyne click
      reaction. The attractive features of this system include facile operation, access
      to unique polymer designs, and no requirement for using excess NaN3. In addition
      to N3-, thiocyanate (-SCN) and cyanate (-OCN) anions were also studied.

PMID- 28741357
TI  - Modular Construction of Protected 1,2/1,3-Diols, -Amino Alcohols, and -Diamines
      via Catalytic Asymmetric Dehydrative Allylation: An Application to Synthesis of
      Sphingosine.
AB  - A new enantioselective catalysis has been developed for the one-step construction
      of methylene-bridged chiral modules of 1,2- and 1,3-OH and/or NH function(s) from
      delta- or lambda-OH/NHBoc-substituted allylic alcohols and "H2C?O"/"H2C?NBoc". A
      protonic nucleophile, either in situ-generated CH2OH or CH2NHBoc, is
      intramolecularly allylated to furnish eight possible 1,2- or 1,3-O,O, -O,N, -N,O,
      and -N,N chiral modules equipped with an ethenyl group in high yields and
      enantioselectivities. The utility of this method has been demonstrated in the
      five-step synthesis of sphingosine.

PMID- 28741358
TI  - Combining De Novo Peptide Sequencing Algorithms, A Synergistic Approach to Boost
      Both Identifications and Confidence in Bottom-up Proteomics.
AB  - Complex mass spectrometry based proteomics data sets are mostly analyzed by
      protein database searches. While this approach performs considerably well for
      sequenced organisms, direct inference of peptide sequences from tandem mass
      spectra, i.e., de novo peptide sequencing, oftentimes is the only way to obtain
      information when protein databases are absent. However, available algorithms
      suffer from drawbacks such as lack of validation and often high rates of false
      positive hits (FP). Here we present a simple method of combining results from
      commonly available de novo peptide sequencing algorithms, which in conjunction
      with minor tweaks in data acquisition ensues lower empirical FDR compared to the
      analysis using single algorithms. Results were validated using state-of-the art
      database search algorithms as well specifically synthesized reference peptides.
      Thus, we could increase the number of PSMs meeting a stringent FDR of 5% more
      than 3-fold compared to the single best de novo sequencing algorithm alone,
      accounting for an average of 11 120 PSMs (combined) instead of 3476 PSMs (alone)
      in triplicate 2 h LC-MS runs of tryptic HeLa digestion.

PMID- 28741359
TI  - Evaluation of Parameters for Confident Phosphorylation Site Localization Using an
      Orbitrap Fusion Tribrid Mass Spectrometer.
AB  - Confident identification of sites of protein phosphorylation by mass spectrometry
      (MS) is essential to advance understanding of phosphorylation-mediated signaling
      events. However, the development of novel instrumentation requires that methods
      for MS data acquisition and its interrogation be evaluated and optimized for high
      throughput phosphoproteomics. Here we compare and contrast eight MS acquisition
      methods on the novel tribrid Orbitrap Fusion MS platform using both a synthetic
      phosphopeptide library and a complex phosphopeptide-enriched cell lysate. In
      addition to evaluating multiple fragmentation regimes (HCD, EThcD, and neutral
      loss-triggered ET(ca/hc)D) and analyzers for MS/MS (orbitrap (OT) versus ion trap
      (IT)), we also compare two commonly used bioinformatics platforms, Andromeda with
      PTM-score, and MASCOT with ptmRS for confident phosphopeptide identification and,
      crucially, phosphosite localization. Our findings demonstrate that optimal
      phosphosite identification is achieved using HCD fragmentation and high
      resolution orbitrap-based MS/MS analysis, employing MASCOT/ptmRS for data
      interrogation. Although EThcD is optimal for confident site localization for a
      given PSM, the increased duty cycle compared with HCD compromises the numbers of
      phosphosites identified. Finally, our data highlight that a charge-state
      dependent fragmentation regime and a multiple algorithm search strategy are
      likely to be of benefit for confident large-scale phosphosite localization.

PMID- 28741360
TI  - Influence of Chemical, Mechanical, and Transport Processes on Wellbore Leakage
      from Geologic CO2 Storage Reservoirs.
AB  - Wells are considered to be high-risk pathways for fluid leakage from geologic CO2
      storage reservoirs, because breaches in this engineered system have the potential
      to connect the reservoir to groundwater resources and the atmosphere. Given these
      concerns, a few studies have assessed leakage risk by evaluating regulatory
      records, often self-reported, documenting leakage in gas fields. Leakage is
      thought to be governed largely by initial well-construction quality and the
      method of well abandonment. The geologic carbon storage community has raised
      further concerns because acidic fluids in the CO2 storage reservoir, alkaline
      cement meant to isolate the reservoir fluids from the overlying strata, and steel
      casings in wells are inherently reactive systems. This is of particular concern
      for storage of CO2 in depleted oil and gas reservoirs with numerous legacy wells
      engineered to variable standards. Research suggests that leakage risks are not as
      great as initially perceived because chemical and mechanical alteration of cement
      has the capacity to seal damaged zones. Our work centers on defining the coupled
      chemical and mechanical processes governing flow in damaged zones in wells. We
      have developed process-based models, constrained by experiments, to better
      understand and forecast leakage risk. Leakage pathways can be sealed by
      precipitation of carbonate minerals in the fractures and deformation of the
      reacted cement. High reactivity of cement hydroxides releases excess calcium that
      can precipitate as carbonate solids in the fracture network under low brine flow
      rates. If the flow is fast, then the brine remains undersaturated with respect to
      the solubility of calcium carbonate minerals, and zones depleted in calcium
      hydroxides, enriched in calcium carbonate precipitates, and made of amorphous
      silicates leached of original cement minerals are formed. Under confining
      pressure, the reacted cement is compressed, which reduces permeability and lowers
      leakage risks. The broader context of this paper is to use our experimentally
      calibrated chemical, mechanical, and transport model to illustrate when, where,
      and in what conditions fracture pathways seal in CO2 storage wells, to reduce
      their risk to groundwater resources. We do this by defining the amount of cement
      and the time required to effectively seal the leakage pathways associated with
      peak and postinjection overpressures, within the context of oil and gas industry
      standards for leak detection, mitigation, and repairs. Our simulations suggest
      that for many damage scenarios chemical and mechanical processes lower leakage
      risk by reducing or sealing fracture pathways. Leakage risk would remain high in
      wells with a large amount of damage, modeled here as wide fracture apertures,
      where fast flowing fluids are too dilute for carbonate precipitation and
      subsurface stress does not compress the altered cement. Fracture sealing is more
      likely as reservoir pressures decrease during the postinjection phase where lower
      fluxes aid chemical alteration and mechanical deformation of cement. Our results
      hold promise for the development of mitigation framework to avoid impacting
      groundwater resources above any geologic CO2 storage reservoir by correlating
      operational pressures and barrier lengths.

PMID- 28741361
TI  - Three-Dimensional Printed Shape Memory Objects Based on an Olefin Ionomer of Zinc
      Neutralized Poly(ethylene-co-methacrylic acid).
AB  - Three-dimensional printing enables the net shape manufacturing of objects with
      minimal material waste and low tooling costs, but the functionality is generally
      limited by available materials, especially for extrusion-based printing, such as
      fused deposition modeling (FDM). Here, we demonstrate shape memory behavior of 3D
      printed objects with FDM using a commercially available olefin ionomer, Surlyn
      9520, which is zinc-neutralized poly(ethylene-co-methacrylic acid). The initial
      fixity for 3D printed and compression-molded samples was similar, but the initial
      recovery was much lower for the 3D printed sample (R = 58%) than that for the
      compression-molded sample (R = 83%). The poor recovery in the first cycle is
      attributed to polyethylene crystals formed during programming that act to resist
      the permanent network recovery. This effect is magnified in the 3D printed part
      due to the higher strain (lower modulus in the 3D printed part) at a fixed
      programming stress. The fixity and recovery in subsequent shape memory cycles are
      greater for the 3D printed part than for the compression-molded part. Moreover,
      the programmed strain can be systematically modulated by inclusion of porosity in
      the printed part without adversely impacting the fixity or recovery. These
      characteristics enable the direct formation of complex shapes of thermoplastic
      shape memory polymers that can be recovered in three dimensions with the
      appropriate trigger, such as heat, through the use of FDM as a 3D printing
      technology.

PMID- 28741362
TI  - Gastroenterology - Evolution of specialty choice in recent years.
AB  - INTRODUCTION: Gastroenterology is one of the medical specialties offered to
      residency training candidates each year. This project analyzes the data
      associated with the choice of a Gastroenterology residency program in recent
      years. MATERIAL AND METHODS: Data related to specialty selection were obtained
      from official reports with regard to the allocation of residency places by the
      Spanish Ministry of Health, Social Services and Equality. Information was
      collected from various teaching centers via their training guides, the Spanish
      National Catalogue of Hospitals and the National Transplant Organization.
      RESULTS: The median consecutive number involved in the choice of Gastroenterology
      training has decreased year after year, and this specialty is now positioned
      among the five most commonly selected residency programs in 2015. The median
      number of hospitals with a higher number of beds, adult liver transplantation
      activities and dedicated GI bleeding units is significantly lower. This is also
      true when centers are analyzed according to the presence of specific
      Gastroenterology on-call shifts for residents or their association with medical
      schools. Data from the past five years highlight Madrid, Aragon and the Basque
      Country as the autonomous communities where Gastroenterology is the most popular.
      Centers selected by candidates with the lowest median consecutive numbers from
      2011-2015 included the university hospitals Ramon y Cajal, Santiago de Compostela
      and Gregorio Maranon. CONCLUSIONS: Gastroenterology has gradually escalated in
      the ranking of residency choices and is now one of the five most popular options.
      Potential residents prefer larger centers with complex-care patients and more
      research activity.

PMID- 28741363
TI  - Bowel obstruction secondary to intraluminal migration of the abdominal wall mesh.
AB  - Eventration is an important public health problem due to its high incidence of
      around 12-15% in all laparotomies performed. The repair of an eventration has a 5
      15% risk of complications. In recent years, the repair with prosthetic material
      has resulted in additional complications.

PMID- 28741364
TI  - Propofol sedation Quality and safety. Failure mode and effects analysis.
AB  - Sedation is a key component of digestive endoscopy. While ensuring procedural
      safety and quality represents a primary goal, a detailed assessment of patient
      focused risks and improvements is lacking on most occasions. Failure mode and
      effect analysis (FMEA) is a useful tool in this context as a means of raising
      barriers and defense mechanisms to prevent adverse events from developing.

PMID- 28741365
TI  - In response to the letter by Cabadas and Alvarez-Escudero about the editorial:
      "Will societies of anesthesiologists partake in the take-off of non
      anesthesiologist administration of propofol?"
AB  - I thank R. Cabadas and J. Alvarez-Escudero (1). 1. Apologies accepted. 2. The
      statistical significance of the difference in proportions seems doubtful. 3.
      Although these small studies do not allow us to confirm the safety of endoscopist
      directed propofol sedation, they deserve a short comment as they represent the
      best available level of evidence (RCTs) and are also informative. 4. Hypoxemia,
      hypotension and bradycardia are frequent and have no clinical consequences in
      most cases. 5. The authors started this chapter by stating "scientific opinions
      must be carefully based" (3); 6. As quotation marks were used, the correct
      reference should have been cited in that paragraph. 7. The point is that, under
      correct conditions as detailed in the ESGE Guidelines (4,5), propofol is as safe
      as midazolam/fentanyl.

PMID- 28741366
TI  - Comparison of bi-exponential and mono-exponential models of diffusion-weighted
      imaging for detecting active sacroiliitis in ankylosing spondylitis.
AB  - Background There has been a growing need for a sensitive and effective imaging
      method for the differentiation of the activity of ankylosing spondylitis (AS).
      Purpose To compare the performances of intravoxel incoherent motion (IVIM)
      derived parameters and the apparent diffusion coefficient (ADC) for
      distinguishing AS-activity. Material and Methods One hundred patients with AS
      were divided into active (n = 51) and non-active groups (n = 49) and 21 healthy
      volunteers were included as control. The ADC, diffusion coefficient ( D),
      pseudodiffusion coefficient ( D*), and perfusion fraction ( f) were calculated
      for all groups. Kruskal-Wallis tests and receiver operator characteristic (ROC)
      curve analysis were performed for all parameters. Results There was good
      reproducibility of ADC /D and relatively poor reproducibility of D*/f. ADC, D,
      and f were significantly higher in the active group than in the non-active and
      control groups (all P < 0.0001, respectively). D* was slightly but significant
      lower in the active group than in the non-active and control group ( P = 0.0064,
      0.0215). There was no significant difference in any parameter between the non
      active group and the control group (all P > 0.050). In the ROC analysis, ADC had
      the largest AUC for distinguishing between the active group and the non-active
      group (0.988) and between the active and control groups (0.990). Multivariate
      logistic regression analysis models showed no diagnostic improvement. Conclusion
      ADC provided better diagnostic performance than IVIM-derived parameters in
      differentiating AS activity. Therefore, a straightforward and effective mono
      exponential model of diffusion-weighted imaging may be sufficient for
      differentiating AS activity in the clinic.

PMID- 28741367
TI  - Radiotherapy Synergizes with the Hypoxia-Activated Prodrug Evofosfamide: In Vitro
      and In Vivo Studies.
AB  - AIMS: Evofosfamide (TH-302) is a hypoxia-activated prodrug (HAP) that releases
      the DNA-damaging bromo-isophosphoramide mustard (Br-IPM) moiety selectively under
      hypoxic conditions. Since solid tumors are known to have hypoxic regions, HAPs in
      combination with chemotherapy or radiotherapy (XRT) will be beneficial. We tested
      the oxygen dependence of release kinetics of Br-IPM using electron paramagnetic
      resonance (EPR) with spin trapping by monitoring redox cycling of the
      nitroimidazole moiety of TH-302, and oxygen dependence of TH-302 on in vitro
      cytotoxicity at different levels of hypoxia was also examined. Two tumor implants
      (SCCVII and HT29) in mice were studied. RESULTS: TH-302 fragmentation to release
      Br-IPM was noticed at oxygen levels <76 mmHg, which increased with higher levels
      of hypoxia. Enhanced cellular cytotoxicity was also observed at oxygen levels <76
      mmHg. In vivo pO2 imaging in the two tumor implants showed that the SCCVII tumor
      implant had higher level of hypoxia compared with the HT29 xenograft. TH-302 as a
      monotherapy in vivo showed modest effects in SCCVII implants and minimal effects
      in HT29 xenografts, whereas TH-302 in combination with ionizing radiation showed
      significant benefit in both tumor models. INNOVATION: We examined the kinetics of
      redox cycling versus fragmentation of TH-302. The combination of oxygen-dependent
      XRT with TH-302 is effective even in tumors with significant hypoxia.
      CONCLUSIONS: Imaging studies identifying the magnitude of hypoxia in tumors
      indicated that the responsiveness to TH-302 and the antitumor effect of TH-302
      were enhanced by combining with XRT in both the TH-302-sensitive SCCVII tumor and
      -resistant HT29 tumor. Antioxid. Redox Signal. 28, 131-140.

PMID- 28741368
TI  - The ontological turn meets the certainty of death.
AB  - The 'ontological turn' involves some anthropological points of long standing but
      the approaches recently coordinated into this turn have been presented as a 'call
      to arms', as shaking up 'mono-realist singularities' and as inherently political.
      This fighting talk has no doubt made important contributions to anthropology and
      insights from the ontological turn can help in anthropological understandings of
      medical practices. However, this paper contends that this helpfulness is also
      limited and that a call to arms may be inappropriate. This point is made through
      an ethnographic understanding of medical concern about the diagnosis of death.

PMID- 28741369
TI  - Bolus Advisors: Sources of Error, Targets for Improvement.
AB  - Bolus advisors that are designed to improve the accuracy of individual bolus
      doses relative to a meal's carb content and the current glucose have not
      substantially changed since they were introduced 15 years ago despite an obvious
      need for enhancement and innovation. Although some glycemic benefits have been
      demonstrated, bolus advisors largely ignore the large amounts of clinical data
      they gather that could have a significant impact on glucose outcomes. Concerns
      have also been raised regarding the aggressive nature of largely unpublished or
      poorly explained bolus advisor algorithms. Hypoglycemia and hyperglycemia remain
      significant risks due to inaccurate bolus advisor settings and the absence of
      tracking or an inappropriate handling of bolus on board. This review covers
      common sources for bolus advisor error such as the selection of physiologically
      inappropriate bolus advisor settings, the use of short duration of insulin action
      times, poor algorithm logic that tends to cover all carb intake fully, and an
      excessive reliance on simplistic dosing algorithms. As well as discussing these
      areas, we provide 21 ways to improve current bolus calculators.

PMID- 28741370
TI  - Non-health care facility anticonvulsant medication errors in the United States.
AB  - INTRODUCTION: This study provides an epidemiological description of non-health
      care facility medication errors involving anticonvulsant drugs. METHODS: A
      retrospective analysis of National Poison Data System data was conducted on non
      health care facility medication errors involving anticonvulsant drugs reported to
      US Poison Control Centers from 2000 through 2012. RESULTS: During the study
      period, 108,446 non-health care facility medication errors involving
      anticonvulsant pharmaceuticals were reported to US Poison Control Centers,
      averaging 8342 exposures annually. The annual frequency and rate of errors
      increased significantly over the study period, by 96.6 and 76.7%, respectively.
      The rate of exposures resulting in health care facility use increased by 83.3%
      and the rate of exposures resulting in serious medical outcomes increased by
      62.3%. In 2012, newer anticonvulsants, including felbamate, gabapentin,
      lamotrigine, levetiracetam, other anticonvulsants (excluding barbiturates), other
      types of gamma aminobutyric acid, oxcarbazepine, topiramate, and zonisamide,
      accounted for 67.1% of all exposures. CONCLUSIONS: The rate of non-health care
      facility anticonvulsant medication errors reported to Poison Control Centers
      increased during 2000-2012, resulting in more frequent health care facility use
      and serious medical outcomes. Newer anticonvulsants, although often considered
      safer and more easily tolerated, were responsible for much of this trend and
      should still be administered with caution.

PMID- 28741373
TI  - Adaptation and validation into Portuguese language of the six-item cognitive
      impairment test (6CIT).
AB  - BACKGROUND: The six-item cognitive impairment test (6CIT) is a brief cognitive
      screening tool that can be administered to older people in 2-3 min. OBJECTIVE: To
      adapt the 6CIT for the European Portuguese and determine its psychometric
      properties based on a sample recruited from several contexts (nursing homes;
      universities for older people; day centres; primary health care units). METHOD:
      The original 6CIT was translated into Portuguese and the draft Portuguese version
      (6CIT-P) was back-translated and piloted. The accuracy of the 6CIT-P was assessed
      by comparison with the Portuguese Mini-Mental State Examination (MMSE). A
      convenience sample of 550 older people from various geographical locations in the
      north and centre of the country was used. RESULTS: The test-retest reliability
      coefficient was high (r = 0.95). The 6CIT-P also showed good internal consistency
      (alpha = 0.88) and corrected item-total correlations ranged between 0.32 and
      0.90. Total 6CIT-P and MMSE scores were strongly correlated. The proposed 6CIT-P
      threshold for cognitive impairment is >=10 in the Portuguese population, which
      gives sensitivity of 82.78% and specificity of 84.84%. The accuracy of 6CIT-P, as
      measured by area under the ROC curve, was 0.91. CONCLUSION: The 6CIT-P has high
      reliability and validity and is accurate when used to screen for cognitive
      impairment.

PMID- 28741371
TI  - Dexamethasone ameliorates H2S-induced acute lung injury by increasing claudin-5
      expression via the PI3K pathway.
AB  - Acute lung injury (ALI) is a major outcome of exposure to high levels of hydrogen
      sulfide (H2S). Dexamethasone (DXM) has been used to treat ALI. However, the
      mechanisms involved in H2S-induced ALI and the protective mechanisms of DXM in
      treating ALI are still nebulous. To explore the mechanisms involved, we evaluated
      the role of claudin-5 in the protective effect of DXM against H2S-induced ALI.
      Sprague-Dawley rats were exposed to H2S to establish the ALI model. In parallel
      with the animal model, a cell model was also established by incubating human
      umbilical vein endothelial cells (HUVECs) with NaHS. Lung hematoxylin-eosin
      staining, electron microscope assay, and wet/dry ratio were used to identify
      whether the ALI was successfully induced by H2S, and changes in claudin-5
      expression were detected in both rats and HUVECs. Our results revealed that
      claudin-5 was markedly decreased after H2S exposure and that DXM significantly
      attenuated the H2S-induced downregulation of claudin-5 in both rats and HUVECs.
      In the animal experiment, p-Akt and p-FoxO1 presented a similar tendency as
      claudin-5, but their levels decreased 6 h prior to the levels of claudin-5. In a
      further investigation, the DXM-induced protective effect on ALI and rescue effect
      on downregulation of claudin-5 were both blocked by LY294002. The current study
      demonstrated that claudin-5 was involved in the development of H2S-induced ALI
      and that DXM exerted protective effects through increasing claudin-5 expression
      by activating the phosphatidylinositol 3-kinase pathway. Therefore, claudin-5
      might represent a novel pharmacological target for treating ALI induced by H2S
      and other hazardous gases.

PMID- 28741374
TI  - Lipid emulsion alleviates the vasodilation and mean blood pressure decrease
      induced by a toxic dose of verapamil in isolated rat aortae and an in vivo rat
      model.
AB  - This study aimed to examine the effects of lipid emulsion on the vasodilation and
      cardiovascular depression induced by toxic doses of calcium channel blockers. The
      effects of lipid emulsion on the vasodilation induced by bepridil, verapamil,
      nifedipine, and diltiazem were investigated in isolated endothelium-denuded rat
      aortae. The effect of lipid emulsion on the comparable hemodynamic depression
      induced by the continuous infusion of a toxic dose of either verapamil or
      diltiazem was examined in an in vivo rat model. The results showed the following
      decreasing order for the magnitude of lipid emulsion-mediated inhibition of
      vasodilation: bepridil, verapamil, nifedipine, and diltiazem. Lipid emulsion (0.5
      2%) reversed the vasodilation induced by a toxic dose of verapamil, whereas only
      a higher concentration (2%) reversed the vasodilation induced by a toxic dose of
      diltiazem. Pretreatment with lipid emulsion alleviated the systolic and mean
      blood pressure decreases induced by a toxic dose of verapamil, whereas it had no
      effect on the decrease induced by diltiazem. Taken together, these results
      suggest that lipid emulsion alleviates the severe vasodilation and systolic blood
      pressure decrease induced by a toxic dose of verapamil, and this alleviation
      appears to be associated with the relatively high lipid solubility of verapamil.

PMID- 28741375
TI  - Comparison of slow and forced vital capacities on ability to predict survival in
      ALS.
AB  - INTRODUCTION: Slow (SVC) and forced (FVC) vital capacities are the most used
      pulmonary function tests in amyotrophic lateral sclerosis (ALS). It is unknown if
      they equally predict survival in ALS. The aim of the present study was to compare
      both measures in predicting survival in this disease. METHODS: Consecutive
      definite/probable ALS patients (2000-2014) in whom respiratory tests were
      performed at baseline and four months later were included. All patients were
      evaluated with the revised ALS functional rating scale (ALSFRS-R), respiratory
      (RofALSFRS-R), bulbar (ALSFRSb), upper and lower limb subscores, SVC, FVC,
      maximal inspiratory (MIP) and expiratory (MEP) pressures. King's functional
      staging system was applied retrospectively. Survival analysis was carried out by
      univariate Kaplan-Meier log-rank test. Multivariate Cox proportional hazards
      model determined significant independent variables. RESULTS: We included 469
      patients (270 males; mean onset age 61.0 +/- 11.5 years; mean disease duration
      from first symptoms to first visit: 15.8 +/- 16.1months; 329 spinal and 140
      bulbar onset). FVC and SVC were strongly correlated (r2 = 0.981, p < 0.001).
      Significant survival prognostic variables (Kaplan-Meier analyses) were onset
      region, age, disease duration, ALSFRS-R, ALSFRSb, RofALSFRS-R, ALSFRS-R decay,
      SVC, FVC, MIP, MEP and King's staging (p <= 0.01). Final Cox model including the
      significant variables showed similar results for FVC and SVC (p < 0.001).
      Moreover, 1% decrease in either predicted values increased death probability by
      1.02. CONCLUSION: FVC and SVC are inter-changeable in predicting survival in ALS.

PMID- 28741376
TI  - Rate of Symptomatic Lymphocele Formation After Extraperitoneal vs Transperitoneal
      Robot-Assisted Radical Prostatectomy and Bilateral Pelvic Lymphadenectomy.
AB  - INTRODUCTION AND OBJECTIVE: With the peritoneum acting as a natural surface for
      lymphatic reabsorption, transperitoneal robot-assisted radical prostatectomy
      (tRARP) is thought to be associated with a lower incidence of symptomatic
      lymphoceles (SLs) compared with its extraperitoneal counterpart (eRARP) when
      bilateral pelvic lymph node dissection (BPLND) is performed. In this study, we
      aim to determine if there is a difference in SL formation and characteristics
      between the two approaches. MATERIALS AND METHODS: We retrospectively reviewed
      the records of patients who underwent eRARP or tRARP and BPLND by a single
      surgeon at a tertiary care academic center from July 1, 2003, to May 31, 2016.
      Patients with a history of prior pelvic radiotherapy, concomitant inguinal hernia
      repair, RARP without BPLND, or nonadenocarcinoma of the prostate were excluded.
      The resulting eRARP and tRARP groups were propensity matched for age, body mass
      index (BMI), American Association of Anesthesiologists (ASA) score, D'Amico risk
      classification, and pathological lymph node (LN) count. RESULTS: A total of 3183
      RARPs were performed during this time period. After applying exclusion criteria
      and propensity score matching, 671 patients remained in each group. No
      statistically significant differences were noted between the groups with regard
      to age, BMI, ASA, pre-RARP prostate-specific antigen, D'Amico risk
      classification, biopsy and pathological Gleason sum score, pathological T stage,
      or margin status. The tRARP group had a higher clinical T stage (p = 0.0015),
      length of stay (LOS; p = 0.005), pathological N stage (4.92% vs 1.36%, p =
      0.0002), and high total LN count (7.22 +/- 5.54 vs 5.78 +/- 4.18 LNs, p <
      0.0001). The eRARP group had higher operating room times (197.4 +/- 48.96 minutes
      vs 192.2 +/- 44.12 minutes, p = 0.04) and estimated blood loss (218.4 +/- 152.0
      mL vs 179.9 +/- 119.4 mL, p < 0.0001). No differences were noted in the frequency
      of SL formation [eRARP: 19/671 (2.83%) vs tRARP: 10/671 (1.49%), p = 0.09] or any
      clinical characteristics of the SL. Logistic regression analysis showed no effect
      of LN count (p = 0.071), pathological N stage (p = 0.111), or both combined (p =
      0.085) on SL formation. CONCLUSIONS: In this cohort, the rate and clinical
      characteristics of SL were similar among patients treated with eRARP or tRARP and
      BPLND. The low event rate of SL in each group and trends favoring higher SL with
      LN yield and pN1 disease in the tRAPR group may deem the study underpowered to
      make definitive conclusions.

PMID- 28741377
TI  - Renal Cell Carcinoma: Alternative Nephron-Sparing Treatment Options for Small
      Renal Masses, a Systematic Review.
AB  - BACKGROUND: The standard treatment of T1 renal cell carcinoma (RCC) is (partial)
      nephrectomy. For patients where surgery is not the treatment of choice, for
      example in the elderly, in case of severe comorbidity, inoperability, or refusal
      of surgery, alternative treatment options are available. These treatment options
      include active surveillance (AS), radiofrequency ablation (RFA), cryoablation
      (CA), microwave ablation (MWA), or stereotactic body radiotherapy (SBRT). In the
      present overview, the efficacy, safety, and outcome of these different options
      are summarized, particularly focusing on recent developments. MATERIALS AND
      METHODS: Databases of MEDLINE (through PubMed), EMBASE, and the Cochrane Library
      were systematically searched according to the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was performed
      in December 2016, and included a search period from 2010 to 2016. The terms and
      synonyms used were renal cell carcinoma, active surveillance, radiofrequency
      ablation, microwave ablation, cryoablation and stereotactic body radiotherapy.
      RESULTS: The database search identified 2806 records, in total 73 articles were
      included to assess the rationale and clinical evidence of alternative treatment
      modalities for small renal masses. The methodological quality of the included
      articles varied between level 2b and level 4. CONCLUSION: Alternative treatment
      modalities, such as AS, RFA, CA, MWA, and SBRT, are treatment options especially
      for those patients who are unfit to undergo an invasive treatment. There are no
      randomized controlled trials available comparing surgery and less invasive
      modalities, leading to a low quality on the reported articles. A case-controlled
      registry might be an alternative to compare outcomes of noninvasive treatment
      modalities in the future.

PMID- 28741378
TI  - Procainamide-induced autoimmunity: Relationship to T-helper 2-type T-cell
      activation.
AB  - Drug-induced autoimmunity (DIA) refers to a group of adverse drug reactions, and
      they remain unpredictable largely due to the limited understanding of the
      mechanisms involved. There is evidence that procainamide can cause autoimmune
      reactions in humans but the mechanisms involved remain unclear. To examine the
      cellular and genetic factors involved in the procainamide-induced autoimmune
      response, we compared rats that are genetically T-helper (Th)2-predisposed (Brown
      Norway (BN)), Th1-predisposed (Lewis (LEW)) or not genetically predisposed
      (Sprague Dawley (SD)). We revealed significant differences in response to
      autoimmunity induced by procainamide among three strains rats, BN was the most
      sensitive one, SD exhibited less sensitive, while LEW resistance to procainamide.
      Much more pronounced of Th2-type responses and more complex differentially
      expressed genes involved in immune regulation and response in BN might contribute
      to its susceptibleness to DIA. Moreover, similar immune mechanisms were found
      between BN and SD, which suggesting that these changes would serve as the
      potential bridge biomarkers to predict DIA among species. This study may also
      benefit to further understand the toxicological mechanism of drug-induced
      autoimmune reactions.

PMID- 28741380
TI  - Genetic Modification of T Cells with Chimeric Antigen Receptors: A Laboratory
      Manual.
AB  - Redirected T cells genetically modified with a chimeric antigen receptor (CAR)
      have induced spectacular remissions of refractory leukemia/lymphoma in early
      phase trials, attracting interest to use CAR T cells in a variety of other
      applications including solid cancer and nonmalignant diseases. However, extensive
      preclinical explorations demand highly effective and robust procedures for the
      genetic modification of blood T cells; the same applies for engineering with a
      recombinant T cell receptor. We present laboratory procedures in a step-by-step
      protocol to engineer human and mouse T cells with a CAR by gamma-retro- or
      lentiviral transduction for further preclinical testing.

PMID- 28741379
TI  - Tiny RNAs and their voyage via extracellular vesicles: Secretion of bacterial
      small RNA and eukaryotic microRNA.
AB  - MicroRNAs are small non-coding RNAs that bind to the 3'-untranslated region of
      target mRNAs and have transcriptional or translational inhibitory function in
      eukaryotes. Before microRNAs were widely known, bacterial non-coding small RNAs
      around 50-200 nt in length were discovered whose mechanism of action resembled
      that of microRNAs. Recently, RNAs that are of similar size to or smaller than
      microRNAs have been discovered in bacteria and indeed, this class of small RNAs
      have been found throughout all domains of life. Moreover, recent findings suggest
      that these tiny RNAs can be released via extracellular vesicles (such as exosomes
      in eukaryotes and outer membrane vesicles in bacteria), which in turn heralds a
      new field of research, interkingdom communication. This review discusses two
      similar classes of small RNAs in evolutionarily distinct eukaryotes and bacteria.
      In addition to their biogenesis and regulation, we discuss small RNA vehicles and
      their secretion. Impact statement The possible endogenous functions of small RNAs
      such as regulatory small RNAs in bacteria and microRNAs in eukaryotes have been
      extensively studied since they were first discovered. However, their powerful
      functions should not be seen as limited to their cells of origin. Recently,
      several papers have demonstrated that small RNAs function as signaling molecules
      between cells. This is possible because small RNAs can be shuttled around after
      being incorporated into environmentally protective extracellular vesicles. It is
      now clearly plausible that secreted small RNAs can regulate other types of cells
      through biofluids. Given their "common molecule" status, the role of small RNAs
      in mediating bacteria-human crosstalk is an emerging and competitive area of
      genetic research. This review provides insight into the function of small RNAs in
      intercellular and even interkingdom communication.

PMID- 28741381
TI  - The relationship between serum ammonia level and neurologic complications in
      patients with acute glufosinate ammonium poisoning: A prospective observational
      study.
AB  - Glufosinate ammonium poisoning can cause neurological complications even after a
      symptom-free period. We prospectively investigated the predictors of neurologic
      complications in acute glufosinate ammonium poisoning and the change of serum
      ammonia level as a predictor of patient's presence and recovery of neurologic
      complication. This prospective observational study collected data from
      consecutive patients diagnosed with acute glufosinate ammonium poisoning between
      September 2014 and June 2016. Serum ammonia was serially measured. The patients
      were divided into two groups: the neurologic complication group and the
      nonneurologic complication group. We also defined 25 other insecticide- or
      herbicide-poisoned patients as controls. The neurologic complication group
      included 18 patients (72.0%). The latency period for neurologic complications was
      within 48-h postingestion. The peak ammonia level was statistically higher in the
      neurologic complication group than in the control group ( p < 0.001) and the
      nonneurologic complication groups ( p = 0.001). There was a statistical
      difference between the nonneurologic complication group and the neurologic
      complication group ( p = 0.0085) in terms of ingested amount. The peak ammonia
      was the only predictor for the development of neurologic complications (the
      optimal cutoff: 90 MUg/dL). In patients with mental changes, the mean serum
      ammonia levels before and after recovery of the mental changes were statistically
      different ( p = 0.0019). In acute glufosinate ammonium poisoning, serial serum
      ammonia level measurements are needed and a serum peak ammonia level greater than
      90 MUg/dL is a predictor of neurologic complications. Also, it is important to
      treat the hyperammonemia in acute glufosinate ammonium poisoning.

PMID- 28741382
TI  - Sodium glucose co-transporter 2 inhibitor luseogliflozin in the management of
      type 2 diabetes: a drug safety evaluation.
AB  - INTRODUCTION: Sodium glucose co-transporter-2 (SGLT2) inhibitors have been
      developed recently as a new class of anti-diabetic drug, and are becoming widely
      used in the management of type 2 diabetes (T2D). As these agents have a
      considerably different glucose-lowering mechanism from those of other anti
      diabetic drugs, safe use of this drug class needs to be discussed based on data
      available from preapproval clinical trials as well as real-world studies. The
      SGLT2 inhibitor luseogliflozin was developed by Taisho Pharmaceutical Co., Ltd.
      and was approved as an oral anti-diabetic drug for T2D in Japan Areas covered:
      The overall safety and efficacy of SGLT2 inhibitor luseogliflozin are summarized
      on the basis of a literature review, with a focus on reported adverse drug
      reactions in preapproval clinical trials and a post-marketing surveillance.
      Expert opinion: SGLT2 inhibitor luseogliflozin is well tolerated, significantly
      improves hyperglycemia in preapproval clinical trials, and has a favorable safety
      profile in both preapproval clinical trials and post-marketing surveillance in
      elderly patients. While long-term safety and efficacy remain to be seen,
      luseogliflozin can benefit T2D patients worldwide. However, healthcare
      professionals must perform appropriate patient education that includes temporary
      withdrawal of luseogliflozin during patient a 'sick day' and avoidance of strict
      carbohydrate restriction during luseogliflozin treatment.

PMID- 28741383
TI  - Adherence to Mediterranean Diet and Metabolic Syndrome in BRCA Mutation Carriers.
AB  - BACKGROUND: Insulin resistance is associated with higher breast cancer (BC)
      penetrance in BRCA mutation carriers. Metabolic syndrome (MetS), an insulin
      resistance syndrome, can be reversed by adhering to the Mediterranean diet
      (MedDiet). In a dietary intervention trial on BRCA mutation carriers, we
      evaluated adherence to the MedDiet, and the association with the MetS, by
      analyzing data from the Mediterranean Diet Adherence Screener (MEDAS). METHODS:
      BRCA mutation carriers, with or without BC, aged 18 to 70 years, were eligible
      for the trial. After the baseline examinations, women were randomized to a
      dietary intervention or to a control group. Both groups completed the MEDAS at
      baseline and at the end of the dietary intervention. RESULTS: A total of 163
      women completed the 6 months of dietary intervention. Compared with controls, the
      women in the intervention group significantly reduced their consumption of red
      meat ( P < .01) and commercial sweets ( P < .01) and their MEDAS score rose
      significantly (+1.3 vs +0.55, P = .02). The number of MetS parameters decreased
      with increasing points of adherence to the MEDAS score ( P = .01). In the
      intervention group, there was a significant association with the greater
      reduction of MetS. CONCLUSION: BRCA mutation carriers in the intervention group
      experienced greater improvement in their MedDiet and MetS parameters.

PMID- 28741384
TI  - Correction to: Chan et al., Three pentacyclic triterpenes protect H9c2
      cardiomyoblast cells against high-glucose-induced injury.

PMID- 28741385
TI  - Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese
      patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind,
      placebo-controlled trial with an open-label period.
AB  - OBJECTIVE: To assess the efficacy and safety of teneligliptin as add-on to
      insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). RESEARCH
      DESIGN AND METHODS: In a 16-week, double-blind period, 148 Japanese T2DM patients
      with inadequate glycemic control with insulin and diet/exercise therapies were
      randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label
      period, all patients received teneligliptin once daily. The primary outcome
      measure was change in HbA1c at the end of the double-blind period. RESULTS: The
      difference between placebo and teneligliptin in change in HbA1c in the double
      blind period (least squares mean +/- SE) was -0.80% +/- 0.11%; teneligliptin was
      superior (ANCOVA, P < 0.001). The HbA1c-lowering effect of teneligliptin was
      maintained throughout the open-label period. The incidence of adverse events was
      53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7%
      in the placebo/teneligliptin group in the open-label period, and 77.9% in the
      teneligliptin/teneligliptin group over both double-blind/open-label periods. The
      incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group
      in the open-label period and 27.3% in the teneligliptin/teneligliptin group over
      both double-blind/open-label periods. CONCLUSION: Teneligliptin was effective and
      well tolerated in Japanese T2DM patients with inadequate glycemic control.
      CLINICAL TRIAL REGISTRATION: NCT02081599.

PMID- 28741386
TI  - Cloning, expression and purification of the alpha-carbonic anhydrase from the
      mantle of the Mediterranean mussel, Mytilus galloprovincialis.
AB  - We cloned, expressed, purified, and determined the kinetic constants of the
      recombinant alpha-carbonic anhydrase (rec-MgaCA) identified in the mantle tissue
      of the bivalve Mediterranean mussel, Mytilus galloprovincialis. In metazoans, the
      alpha-CA family is largely represented and plays a pivotal role in the deposition
      of calcium carbonate biominerals. Our results demonstrated that rec-MgaCA was a
      monomer with an apparent molecular weight of about 32 kDa. Moreover, the
      determined kinetic parameters for the CO2 hydration reaction were kcat =  4.2 *
      105 s-1 and kcat/Km of 3.5 * 107 M-1 *s-1. Curiously, the rec-MgaCA showed a very
      similar kinetic and acetazolamide inhibition features when compared to those of
      the native enzyme (MgaCA), which has a molecular weight of 50 kDa. Analysing the
      SDS-PAGE, the protonography, and the kinetic analysis performed on the native and
      recombinant enzyme, we hypothesised that probably the native MgaCA is a
      multidomain protein with a single CA domain at the N-terminus of the protein.
      This hypothesis is corroborated by the existence in mollusks of multidomain
      proteins with a hydratase activity. Among these proteins, nacrein is an example
      of alpha-CA multidomain proteins characterised by a single CA domain at the N
      terminus part of the entire protein.

PMID- 28741387
TI  - Baseline characteristics and treatment patterns of patients with schizophrenia
      initiated on once-every-three-months paliperidone palmitate in a real-world
      setting.
AB  - OBJECTIVES: Since May 2015, adult patients with schizophrenia adequately treated
      with once monthly paliperidone palmitate (PP1M) may be transitioned to once-every
      three-months paliperidone palmitate (PP3M). This study aims to describe baseline
      characteristics and treatment patterns of patients with schizophrenia initiated
      on PP3M in a real-world setting. METHODS: Pharmacy and medical claims from May
      2014 to September 2016 for adult patients with schizophrenia initiated on PP3M
      (index date) in the Symphony Health Solutions database were analyzed. The cohort
      consisting of all patients and the one restricted to those transitioning from
      PP1M as per prescribing guideline recommendations were considered. Baseline
      characteristics were assessed during the 12 month baseline period. PP1M treatment
      patterns, proportion of days covered (PDC) by mental-health-related medications,
      and healthcare resource utilization (HRU) patterns were evaluated for each
      baseline quarter. PP3M treatment patterns were assessed post-index. RESULTS:
      Among the 1545 adult patients initiated on PP3M who formed the first cohort,
      68.8% transitioned from PP1M based on prescribing guidelines and on an adaptation
      of the strict clinical trial protocol for PP1M to PP3M transition, forming the
      second cohort. In both cohorts, the proportion of patients with a PDC >=80% for
      antipsychotics, antidepressants, anxiolytics, and mood stabilizers increased
      while the proportion of patients with >=1 emergency room, inpatient, or
      outpatient visit decreased in baseline quarters closer to PP3M initiation. Among
      patients with >=4 months of follow-up after the first dose, 85-88% had a second
      dose. Similarly, among those with >=4 months of follow-up after the second dose,
      87-90% received a third dose. CONCLUSIONS: Patients initiated on PP3M
      demonstrated decreased HRU and increased adherence in quarters closer to PP3M
      initiation, and were persistent on their PP3M treatment.

PMID- 28741389
TI  - Corrigendum.

PMID- 28741388
TI  - Comparative Proteomic Analysis of the Effect of the Four-Herb Chinese Medicine
      ANBP on Promoting Mouse Skin Wound Healing.
AB  - Traditional Chinese medicine has great potential to improve wound healing. ANBP,
      the mixture of 4 Chinese herbs- Agrimoniapilosa, Nelumbonucifera,
      Boswelliacarteri, and Pollen typhae-is effective in trauma treatment while its
      mechanism is still elusive. In this study, quantitative proteomics and
      bioinformatics analyses were performed to decipher the possible roles of ANBP in
      accelerated wound healing of mouse skin. Among all 3171 identified proteins, 90,
      71, 80, and 140 proteins were found to be differently expressed in 6 hours, 3
      days, 7 days, and 14 days ANBP-treated tissues compared with corresponding
      control tissues, respectively. The result showed that different biological
      processes and pathways were activated at different healing stages. At the early
      healing stage, ANBP treatment mainly affected several biological processes,
      including immune and defense response, vascular system restoration, hemostasis
      and coagulation regulation, lipid metabolism and signal transduction, while
      muscle tissue, hair, epidermis, extracellular matrix and tissue remodeling
      related activities were the major events in ANBP promoted later wound healing.
      This is the first quantitative proteome study of ANBP-treated wound tissues,
      which provide a new perspective for the mechanism of ANBP accelerated wound
      healing and is of guiding significance for clinical application of ANBP in trauma
      disorders cure.

PMID- 28741390
TI  - Maternal haemoglobin concentration and risk of preterm birth in a Chinese
      population.
AB  - The aim was to examine the relationship between maternal haemoglobin (Hb)
      concentrations and risk of preterm birth by secondary analysis of data from a
      randomised controlled trial. This analysis included 10,430 women who were at
      least 20 years old and no more than 20 weeks of gestation. Results revealed
      neither first- nor second-trimester Hb concentrations were associated with the
      risk of preterm births. However, the risk of preterm birth increased when the Hb
      level was low (<130 g/L) in the first but high (>=130 g/L) in the second
      trimester, regardless of supplement type (iron-containing: AOR: 2.26, 95% CI:
      1.37-3.73; non-iron-containing: AOR: 2.16, 95% CI: 1.11-4.21). In conclusion,
      maternal Hb concentrations were not associated with the risk of preterm birth. A
      low-Hb level in the first trimester but coupled with a high Hb level in the
      second was associated with an elevated risk of preterm birth. Impact statement
      What is already known on this subject: The relationship between maternal Hb
      concentration and preterm birth remains inconclusive. Some studies have shown an
      association between a low- or a high-Hb level and an increased risk of preterm
      birth. Others have not found such an association. Yet others have shown a U
      shaped relationship. What do the results of this study add: Overall, maternal Hb
      concentrations in first or second trimester were not statistically associated
      with the risk of preterm birth. However, women with a low Hb concentration in the
      first trimester together with a high Hb concentration in the second trimester had
      an increased risk of preterm birth, compared to women who had a higher Hb
      concentration in the first trimester that remained similar during the second
      trimester. What are the implications are of these findings for clinical practice
      and/or further research: Our finding helps identify mothers who are at risk of
      having a preterm delivery. Investigating the underlying clinical causes of the
      unfavourable change in Hb levels and close follow-up to these women may help
      improve birth outcomes.

PMID- 28741391
TI  - Clinical implications, benefits and pitfalls of using and reversing non-vitamin K
      antagonist oral anticoagulants.
AB  - INTRODUCTION: The use of non-Vitamin K antagonist oral anticoagulant (NOAC) drugs
      is increasingly common in clinical practice. As compared to vitamin K antagonists
      they are more straightforward to initiate, require no hematological monitoring
      and offer potentially more stable therapeutic indices. Concern has been raised
      with regard to their safety profiles particularly in the context of acute
      reversal in major bleeding. Further issues pertain to patient concordance. Areas
      covered: This review article aims to provide an overview of the current evidence
      relating to NOAC safety as well as the management of NOAC-related major bleeding
      with particular emphasis on reversal agents in use and in development following a
      selective literature review. Second, the effects of medication concordance and
      dosing regimens on NOAC efficacy will be considered. Expert commentary: The short
      half-lives and low overall bleeding risk of NOACs is likely to mean that specific
      reversal agents in development are infrequently required and costly with
      associated practicality issues with their use in clinical emergencies. Concern
      regarding patient concordance can be practicably addressed with appropriate
      medication, dosing regimen and patient selection and continuous education with
      active, informed patient involvement in the decision-making process.

PMID- 28741392
TI  - Recent advances in the development and use of molecular tests to predict
      antimicrobial resistance in Neisseria gonorrhoeae.
AB  - INTRODUCTION: The number of genetic tests, mostly real-time PCRs, to detect
      antimicrobial resistance (AMR) determinants and predict AMR in Neisseria
      gonorrhoeae is increasing. Several of these assays are promising, but there are
      important shortcomings and few assays have been adequately validated and quality
      assured. Areas covered: Recent advances, focusing on publications since 2012, in
      the development and use of molecular tests to predict gonococcal AMR for
      surveillance and for clinical use, advantages and disadvantages of these tests
      and of molecular AMR prediction compared with phenotypic AMR testing, and future
      perspectives for effective use of molecular AMR tests for different purposes.
      Expert commentary: Several challenges for direct testing of clinical, especially
      extra-genital, specimens remain. The choice of molecular assay needs to consider
      the assay target, quality controls, sample types, limitations intrinsic to
      molecular technologies, and specific to the chosen methodology, and the intended
      use of the test. Improved molecular- and particularly genome-sequencing-based
      methods will supplement AMR testing for surveillance purposes, and translate into
      point-of-care tests that will lead to personalized treatments, while sparing the
      last available empiric treatment option (ceftriaxone). However, genetic AMR
      prediction will never completely replace phenotypic AMR testing, which detects
      also AMR due to unknown AMR determinants.

PMID- 28741393
TI  - Psychometric Properties in Forensic Application of the Screening Version of the
      Psychopathy Checklist.
AB  - The Psychopathy Checklist: Screening Version (PCL: SV) is a short form of the
      Psychopathy Checklist-Revised (PCL-R), an expert-rated assessment that measures
      psychopathic personality traits in research, clinical, and community settings.
      The PCL-R is an extensively relied upon tool in psycho-legal contexts. The
      screening version is also widely used; however, it has received far less
      empirical attention than the PCL-R. This review examines the psychometric
      properties of the PCL: SV, specifically in relation to forensic samples, and
      evaluates its comparability with the full PCL-R. Previously reported similarity
      in the reliability and validity of the PCL: SV as established for the PCL-R was
      supported through further testing in forensic samples. However, limitations in
      terms of available normative data are highlighted, and the review engages with
      wider debate concerning the measurement of psychopathy.

PMID- 28741394
TI  - Predictors of Intervention Success in a Sports-Based Program for Adolescents at
      Risk of Juvenile Delinquency.
AB  - To prevent juvenile delinquency, there is growing interest in the use of sports
      based interventions. To date, there is little empirical research that provides
      insights into for whom, how, and when sports-based crime prevention programs are
      most effective. Therefore, the current study assessed which youth, coach, and
      context factors were predictive of change in risk factors and protective factors
      for delinquency in a sports-based crime prevention program for at-risk
      adolescents. Participants ( N = 155) and their teachers filled in questionnaires
      about risk and protective factors for delinquency at the start of the
      intervention and 13 months later. In addition, the coaches and participants
      filled in questionnaires about the predictors of intervention success. The youths
      showed significant improvements over the course of the intervention. Various
      youth, coach, and context factors (e.g., the type of education of youth and the
      sociomoral climate at the sports club) were associated to change in the outcome
      variables.

PMID- 28741395
TI  - Predictive value of the age-adjusted Charlston co-morbidity index on peri
      operative complications, adjuvant chemotherapy usage and survival in patients
      undergoing debulking surgery after neo-adjuvant chemotherapy for advanced
      epithelial ovarian cancer.
AB  - The aim of this study was to determine whether the age-adjusted Charlston co
      morbidity index (ACCI) can predict post-operative complications, adjuvant
      chemotherapy usage and overall survival (OS) in patients with advanced epithelial
      ovarian cancer (AOC) treated with neoadjuvant chemotherapy (NACT). A review was
      performed of all cytoreductive surgeries performed between 16/8/07-3/2/14 for AOC
      at a UK Cancer Centre. All surgeries were stratified by ACCI into three groups:
      Low (0-1), Intermediate (2-3) and High (>=4). Of the 293 cases the ACCI
      distribution was: 74 (25.26%) low, 164 (55.97%) intermediate and 55 (18.77%)
      high. Patients with a high ACCI were less likely to receive adjuvant chemotherapy
      (p = .023), more likely to receive fewer adjuvant cycles (p = .0057) but no more
      likely to experience complications. Median OS for patients with a low,
      intermediate and high ACCI was 44.58 (95%CI 36.98-52.19), 34.65 (95%CI 29.48
      39.82) and 33.37 (95%CI 17.47-49.27) months. ACCI was associated with OS (p <
      .01) confirmed on multivariate analysis (p = .03). The ACCI is, therefore, a
      marker of survival in these patients and predicts adjuvant chemotherapy usage.
      Impact statement The Age-Adjusted Charlston Co-morbidity Index has previously
      been identified as a predictor of survival in both medical and surgical
      conditions. Recently it has also been validated in patients undergoing primary
      cytoreductive surgery for advanced ovarian cancer. This study is the first to
      validate the Age-Adjusted Charlston Co-morbidity Index in patients undergoing
      cytoreductive surgery following neoadjuvant chemotherapy. Our findings
      demonstrate that it can be used to not only predict overall survival in women
      undergoing debulking surgery after neo-adjuvant chemotherapy but also predicts
      the uptake and commencement of adjuvant chemotherapy. Such findings are important
      considerations to enable an informed patient choice regarding interval surgery in
      the more co-morbid patients. More importantly, although the ACCI can be used as a
      marker of overall survival, even in the most co-morbid of patients there remains
      a significant survival advantage following surgery to the extent that it should
      not be contraindicated in this cohort. The ACCI is being increasingly
      incorporated into various clinical trials as a standard demographic measure and
      this study validates its inclusion in patients undergoing interval debulking
      surgery.

PMID- 28741396
TI  - Intraoperative nerve monitoring reduces recurrent laryngeal nerve injury in
      geriatric patients undergoing thyroid surgery.
AB  - OBJECTIVE: This research was aimed to investigate whether the intraoperative
      nerve monitoring (IONM) can reduce the incidence of recurrent laryngeal nerve
      (RLN) injury in geriatric patients undergoing thyroid surgery. METHODS: This
      retrospective cohort study included 522 geriatric patients undergoing thyroid
      surgery between January 2013 and June 2016 in the Sun Yat-sen Memorial Hospital.
      Patients with IONM during the surgery (n = 340) were compared with patients
      without IONM (n = 212). RLN injury was verified by direct or indirect
      laryngoscope and relative factors for injury would be retrospectively analyzed.
      RESULTS: The use of IONM group showed significant reduction in both total and
      transient RLN injury incidence, when compared with that in control group (1.76
      versus 4.72%, p = .01 and 1.32 versus 3.67%, p = .03, respectively). However, the
      permanent RLN injury incidence did not show difference between the two groups (p
      = .3). CONCLUSIONS: Our finding showed the use of IONM resulted in significantly
      reduction in RLN injury incidence. The technology of IONM is safe and convenient
      to detect, track and monitor the complete function of RLN and to provide the
      guidance for the surgeons during the thyroid surgery in geriatric patients, who
      are at high risk of RLN injury.

PMID- 28741397
TI  - Survival and prognostic factors at time of diagnosis in high-grade appendicular
      osteosarcoma: a 21 year single institution evaluation from east Denmark.
AB  - BACKGROUND: Survival of patients with high-grade osteosarcoma (HOS), the most
      common primary bone cancer, has not improved significantly the last 30 years and
      the disease remains a major challenge. The purpose of this study is to evaluate
      survival in relation to prognostic factors at time of diagnosis among patients
      diagnosed with primary appendicular HOS in East Denmark between 1990 and 2010.
      MATERIAL AND METHODS: 101 patients (median age = 20 years, female/male ratio =
      56/45) diagnosed with primary appendicular high-grade osteosarcoma between 1990
      and 2010 were included in this study. Initially, 156 patients diagnosed with
      osteosarcoma between 1990 and 2010 were identified through the population based
      Regional Database of Pathology, which covers a population of approximately 2.7
      million (east Denmark). 55 patients were excluded due to (A) tumor was low grade
      (n = 22), (B) located in axial skeleton (n = 18), (C) incorrect diagnosis (n =
      11) or (D) biopsy represented a tumor relapse from a former primary osteosarcoma
      (n = 4). Overall survival was evaluated using the Kaplan-Meier survival analysis
      and log-rank test. Prognostic factors were analyzed using uni- and multivariate
      cox-regression method with variables scored equally in the model. p Values <.05
      were considered statistically significant. RESULTS: The probability of 5- and 10
      year survival was 51% (95% CI: 41-61) and 46% (95% CI: 36-56), respectively.
      Metastatic stage at diagnosis and tumor size >=10 cm measured radiologically at
      the largest diameter were independent prognostic factors for decreased survival
      with significant increased hazard-risks of 3.5 (95% CI: 1.9-6.5) and 1.97 (95%
      CI: 1.1-3.6), respectively. DISCUSSION: In this single institution evaluation of
      primary appendicular HOS we found 5-and 10-year survival rates consistent with
      international standards for this patient group. Distant metastases and tumor size
      >=10 cm at the time of diagnosis were independent prognostic factors for
      decreased survival in our cohort. These results underline the importance of
      awareness and early referral from the primary sector.

PMID- 28741398
TI  - Effects of Role-Playing Scenarios on the Self-efficacy of Students in Resisting
      Against Substance Addiction: A Pilot Study.
AB  - During the first phases of adolescent development, young people have little self
      efficacy and resistance against substance use. The aim of this study was to
      demonstrate the effectiveness of role-playing scenarios on the self-efficacy of
      students in resisting substance use. A pre test and post test study design was
      used with a single group. The study was carried out with 245 secondary school
      students. The scenario-based training, developed by the researchers, was
      presented by the school counselors once a week for 4 weeks. For this purpose, a
      booklet of scenarios was prepared for the teachers. The role-playing scenarios
      were intended to improve adolescents' abilities to say "no" to substance offers,
      to prevent them from becoming addicted to certain substances, and to call for
      help if needed. The data of the study were collected using the Personal
      Information Form and the Self-Efficacy for Adolescences Protecting Substance
      Abuse Scale . The obtained data were assessed using percentages, chi-square, t
      test, and F test in the SPSS software. Results showed that, after the training,
      the mean score in the Self-Efficacy for Adolescences Protecting Substance Abuse
      Scale increased significantly (103.20 +/- 20.00) compared with before the
      training (92.11 +/- 17.08) ( P < .05). Short-term outcomes of the class-based
      scenario training were observed to be effective in the development of students'
      self-efficacy to resist the temptations of substance use.

PMID- 28741399
TI  - Incidence of pancreatic cancer in Denmark: 70 years of registration, 1943-2012.
AB  - BACKGROUND: The aim of this study was to monitor the evolution of the incidence
      of pancreatic cancer in Denmark over 70 years. We also compared registrations of
      pancreatic cancer in a nationwide population-based database, the Danish Cancer
      Registry, and a clinical database, the Danish Pancreatic Cancer Database, in 2012
      2013. MATERIAL AND METHODS: Registrations of pancreatic cancer from the Danish
      Cancer Registry over 1943-2012 were used to calculate age-specific incidence
      rates per 100 000 person years by sex and age in 5-year period, weighted by the
      Segi World Standard Population for age standardization. We used absolute numbers
      from the Cancer Registry and the Pancreatic Cancer Database, including
      distribution of topography of cancers registered in 2012-2013, to compare
      registration in the two data sources. RESULTS: The incidence rates of pancreatic
      cancer among Danish men increased until 1968-1972, when a decrease was observed
      until the mid-1990s. A similar peak was observed in women a decade later but
      generally at lower incidence. After the mid-1990s, the incidence rates for both
      sexes increased until the end of the study period. In our comparison of
      registrations in the Cancer Registry and the Pancreatic Cancer Database in 2012
      2013, we found that 29% of the incident cases registered in the Cancer Registry
      were not in the Database; and 11% of the incident cases registered in the
      Database, were not registered in the Cancer Registry. CONCLUSIONS: The incidence
      of pancreatic cancer increased steadily during the last 20 years of our study
      period in both sexes. The differences in registration of incident cases in the
      Cancer Registry and in the Pancreatic Cancer Database indicate underreporting of
      incident cases of pancreatic cancer in Denmark. The magnitude of this
      underreporting cannot be estimated based on this data.

PMID- 28741400
TI  - High Prevalence of Dysgraphia in Elementary Through High School Students With
      ADHD and Autism.
AB  - OBJECTIVE: Prevalence of dysgraphia by age across all grade levels was determined
      in students with ADHD or autism. METHOD: Referred children with normal
      intelligence and ADHD-Combined, ADHD-Inattentive, or autism ( N = 1,034) were
      administered the Developmental Test of Visual-Motor Integration (VMI) and
      Wechsler Intelligence Scale for Children (WISC). RESULTS: VMI and WISC Coding
      scores were significantly lower than IQ and the normal mean of 100 for all
      diagnoses. More than half (59%) had dysgraphia, and 92% had a weakness in
      graphomotor ability relative to other abilities. Dysgraphia prevalence did not
      differ between diagnostic or age groups (6-7 years, 56%; 8-10 years, 60%; and 11
      16 years, 61%). CONCLUSION: Dysgraphia is common at all ages in children and
      adolescents with ADHD and autism. Accommodations and strategies for addressing
      this problem are discussed.

PMID- 28741401
TI  - Trans-diagnostic comparison of response inhibition in Tourette's disorder and
      obsessive-compulsive disorder.
AB  - OBJECTIVES: Impaired response inhibition is related to neurodevelopmental
      disorders, such as Tourette's disorder (TD) and obsessive-compulsive disorder
      (OCD). Unlike OCD, in which neural correlates of response inhibition have been
      extensively studied, TD literature is limited. By using a Stop-Signal task, we
      investigated the neural mechanisms underlying response inhibition deficits in TD
      compared to OCD and healthy controls (HCs). METHODS: Twenty-three TD patients, 20
      OCD patients and 22 HCs were scanned (3T MRI). Region-of-interest analyses were
      performed between TD, OCD and HCs. RESULTS: Performance was similar across all
      subject groups. During inhibition TD compared with HCs showed higher right
      inferior parietal cortex (IPC) activation. During error processing TD compared
      with HCs showed hyperactivity in the left cerebellum, right mesencephalon, and
      right insula. Three-group comparison showed an effect of group for error-related
      activation in the supplementary motor area (SMA). Post-hoc analyses showed higher
      error-related SMA activity in TD compared with OCD and HCs. Error-related left
      cerebellar activity correlated positively with tic severity. CONCLUSIONS:
      Hyperactivation of IPC during inhibition and a widespread hyperactivated network
      during error processing in TD suggest compensatory inhibition- and error-related
      circuit recruitment to boost task performance. The lack of overlap with
      activation pattern in OCD suggests such compensatory mechanism is TD-specific.

PMID- 28741402
TI  - Bipolar dissection technique in parotid gland surgery.
AB  - BACKGROUND: Parotid gland surgery (PGS) has to manage the balancing act between
      sufficient radicality and preservation of functional structures. While many
      studies evaluate post-therapeutic complication due to different extent of
      surgery, the current study introduces bipolar dissection (BP) being a fast and
      safe preparation technique. METHODS: Analysis of clinical parameters (age, sex,
      tumour entity, treatment modalities, facial nerve palsy, bleeding, saliva fistula
      and Frey's syndrome) of 319 consecutively included patients who underwent
      extracapsular dissection and superficial/total/radical parotidectomy. Subgroup
      analysis was done according to the preparation technique (cold vs BP). RESULTS:
      Facial nerve palsy rate increased with the extent of PGS (p < .0001). There were
      no differences in the risk of post-operative bleeding, salivary fistula and
      Frey's syndrome. BP resulted in a significant reduction of operation time (p =
      .04), postoperative bleeding (p = .001) and salivary fistula (p = .045) when
      compared with cold preparation. CONCLUSIONS: Ubiquitous available BP allows fast
      and safe PGS regardless its extent.

PMID- 28741403
TI  - Comparative study between the caloric vestibular and the video-head impulse tests
      in unilateral Meniere's disease.
AB  - OBJECTIVE: Compare the caloric vestibular test (CVT) and the video head impulse
      test (vHIT) in the evaluation of Meniere's disease (MD) and to analyze their
      diagnostic accuracy. MATERIALS AND METHODS: Retrospective review of CVT and vHIT
      performed in MD patients at a tertiary care referral center in Spain. RESULTS: A
      total of 88 patients were reviewed. The CVT was abnormal in 67% (n = 59) of
      patients, while the vHIT was abnormal in 66% (n = 58) of them. Agreement between
      both tests was poor, regardless of whether the horizontal semicircular canal
      (SCC) or all SCC were analyzed (kappa = .21). Anterior SCC pathology was found in
      30% (n = 27) of the subjects while 51% (n = 45) had altered gains in the
      posterior SCC. CONCLUSIONS: Our study shows that patients with MD can have
      functional deficit involving the vertical semicircular canals, which cannot be
      detected by the CVT alone. Therefore, both tests should be used in a
      complementary fashion.

PMID- 28741404
TI  - Simultaneous Real-Time Analysis of Bulk and Bottom Cure of Ultraviolet-Curable
      Inks Using Fourier Transform Infrared Spectroscopy.
AB  - The curing characteristics of an ultraviolet (UV) ink layer are of utmost
      importance for the development of UV inks. Measuring either bulk or bottom cure
      in itself is not new and has been the subject of many articles. In this article,
      two methods are described based on Fourier transform infrared (FT-IR)
      spectrometry to measure in real time and simultaneously the bulk and bottom cure
      of a thin UV ink layer. The procedure consists of applying a thin (10-12 um)
      layer of UV-curing ink on an attenuated total reflection (ATR) crystal. The
      bottom cure is measured with ATR. The bulk cure is measured simultaneously with a
      reflection analysis (method 1) or a transmission analysis (method 2). With both
      methods, the bulk and bottom cure can be determined. To overcome problems with
      the interference in the ATR reflection setup, it is recommended to use the ATR
      transmission setup.

PMID- 28741405
TI  - Optimized tPA: A non-neurotoxic fibrinolytic agent for the drainage of
      intracerebral hemorrhages.
AB  - Intracerebral hemorrhage (ICH) is the most severe form of stroke. Catheter
      delivered thrombolysis with recombinant tissue-type plasminogen activator (rtPA)
      for the drainage of ICH is currently under evaluation in a phase III clinical
      trial (MISTIE III). However, in a pig model of ICH, in situ fibrinolysis with
      rtPA was reported to increase peri-lesional edema by promoting N-methyl-D
      aspartate (NMDA)-dependent excitotoxicity. In the present study, we engineered a
      non-neurotoxic tPA variant, OptPA, and investigated its safety and efficacy for
      in situ fibrinolysis in a rat model of ICH. Magnetic resonance imaging analyses
      of hematoma and edema volumes, behavioral tasks and histological analyses were
      performed to measure the effects of treatments. In vitro, OptPA was equally
      fibrinolytic as rtPA without promoting NMDA-dependent neurotoxicity. In vivo, in
      situ fibrinolysis using OptPA reduced hematoma volume, like rtPA, but it also
      reduced the evolution of peri-hematomal neuronal death and subsequent edema
      progression. Overall, this preclinical study demonstrates beneficial effects of
      OptPA compared to rtPA for the drainage of ICH.

PMID- 28741406
TI  - Balanced (endoscopic medial and transcutaneous lateral) orbital decompression in
      Graves' orbitopathy.
AB  - BACKGROUND: To determine the clinical outcomes and morbidity of endoscopic medial
      wall combined with transcutaneous lateral orbital wall decompression in Graves'
      orbitopathy. METHODOLOGY: A retrospective noncomparative case series of patients
      who underwent surgical decompression for Graves' orbitopathy at Hospital
      Universitario de Fuenlabrada between 2004 and 2014 was performed. We reviewed the
      patients' charts and analyzed before and after the decompression, the visual
      acuity (Snellen chart), optic nerve compression (fundoscopy and optic coherence
      tomography), exophthalmometry (Hertel measurement), ocular motility, diplopia,
      eyelid surgery needed after decompression and its possible complications.
      RESULTS: A total of 20 patients (36 orbits) were operated. The mean follow-up was
      44 months (range 18-84). Vision improved dramatically in all compressive optic
      neuropathy cases (5 cases). Hertel measurements improved on average 3.5 mm (range
      1.5-4.5). Diplopia was cured in eight patients (40%) and nine patients with
      severe preoperative diplopia required strabismus surgery after decompression.
      Eyelid surgery was further needed in 13 patients. Hyaluronic acid injection was
      the most used technique for the treatment of eyelid retraction (6 out of 13
      patients). Only two major complications were observed: one case had a major post
      operative epistaxis and another a cerebrospinal fluid leak. Both were resolved
      without further sequelae. CONCLUSIONS: These results suggest that endoscopic
      medial wall combined with transcutaneous lateral wall orbital decompression is an
      effective and safe treatment for the symptomatic dysthyroid eye disease with
      important proptosis or compressive optic neuropathy.

PMID- 28741407
TI  - Pericytes secrete pro-regenerative molecules in response to platelet-derived
      growth factor-BB.
AB  - Brain pericytes not only maintain the anatomical, biochemical and immune blood
      brain barrier, but display features of mesenchymal stem cells (MSCs) in vitro.
      MSCs have pro-regenerative properties attributed to their secretome. However,
      whether also brain pericytes possess such pro-regenerative capacities is largely
      unknown. Here we characterize the secretome and microvesicle (MV) release of
      human brain pericytes mediated by platelet-derived growth factor-BB (PDGF
      BB)/PDGF receptor beta (PDGFRbeta) signalling. Upon PDGF-BB, pericytes release
      not only a plethora of growth factors and a panel of cytokines, but also MVs
      containing BDNF, FGFb, betaNGF, VEGF and PLGF, a response that is specific for
      PDGFRbeta signalling and activation of the ERK 1/2 pathway. In contrast,
      lipopolysaccharide (LPS), an activator of the innate immune system, stimulates
      the secretion of much higher amounts of mainly inflammatory cytokines and
      activates the NFkappaB pathway. Pericytes change their morphology and undergo
      opposite changes in surface marker expression, respectively. Our findings provide
      evidence that the secretome of human brain pericytes varies greatly depending on
      the exogenous stimulus. The differential secretory functions of pericytes may
      play an important role in either regulating neuroinflammation or contributing to
      neurorestoration and identify a possible new target cell for neuroregeneration.

PMID- 28741408
TI  - Appropriateness of Tympanostomy Tubes in the Boston Metropolitan Area: Are the
      AAO-HNSF Guidelines Being Met?
AB  - Introduction Otitis media (OM) is the most common reason children receive general
      anesthesia, with bilateral tympanostomy tube (TT) insertion the second most
      common surgery in children. Prior research suggests overuse of TT. As part of a
      project designed to improve appropriateness of OM referrals, we evaluated
      appropriateness of TT insertion in a patient cohort. Methods Patients younger
      than 9 years with initial otolaryngology (ORL) visits in academic and private
      office settings for OM from January 1, 2012, to August 31, 2013, were identified
      through claims database. A detailed retrospective chart review of patients
      undergoing TT insertion was performed to determine appropriateness of TT
      insertion per the 2013 American Academy of Otolaryngology-Head and Neck Surgery
      Foundation (AAO-HNSF) guidelines. Results A total of 120 patients undergoing TT
      insertion were randomly chosen for detailed chart review; 32 patients were
      excluded. Sixty-six (75%) of 88 patients available for analysis met AAO-HNSF
      guidelines for TT. Recurrent acute OM with middle ear effusion was the most
      common indication (56%). Other indications included chronic OME and TT in at-risk
      patients with speech, learning, or behavioral delays. Of the 22 patients
      undergoing TT insertion not meeting AAO-HNSF guidelines, 11(50%) had abnormal
      exams, but were 1 to 2 infections short of meeting guidelines; 7 (33%) had normal
      exams but met criteria for number of infections. Discussion Contrary to prior
      publications, 75% of patients undergoing TT insertion had an appropriate
      indication per AAO-HNSF guidelines. In only 5% was TT insertion a substantial
      departure from guidelines. Implications for Practice The study outcomes suggest
      appropriate clinical decision making, improved guideline adherence, and better
      guideline applicability from the previously published 1994 and 2004 guidelines.

PMID- 28741409
TI  - Foxp3 expression in lymph node metastases in patients with head and neck cancer.
AB  - INTRODUCTION: The prevalence and activity of regulatory T cells in patients with
      cancer correlates with poor prognosis. These cells are characterized by their
      expression of Forkhead box protein-3 (Foxp3). Squamous cell carcinoma is the most
      prevalent type of cancer in the head and neck region with overall poor survival
      rates, also due to early spread of metastatic cells. MATERIAL AND METHODS:
      Primary tumor specimens as well as lymph node specimens harvested during neck
      dissection of 65 patients with a diagnosis of HNSCC were subjected to
      immunohistochemical and H-score analysis of Foxp3 expression. Demographics,
      diagnoses, histopathology and subsequent outcome were analyzed. RESULTS: The
      primary cancer was squamous cell carcinoma in all patients (male/female 55:10)
      with the following tumor locations: oral cavity n = 16, oropharynx n = 28,
      hypopharynx n = 11 and larynx n = 10 (Stage III n = 18; Stage IVA n = 45; Stage
      IVB n = 2). The H-score for Foxp3 expression in the primary lesion as well as
      metastatic lymph nodes was significantly higher in advanced stages compared to
      early stages with differences among tumor locations, which were not significant.
      High Foxp3 expression was associated with inferior overall survival rates at a
      mean follow-up of 83.4 months (6-204 months) Conclusions: Foxp3 expression in
      HNSCC varied from the anatomical site and correlated positively with tumor stage
      and was associated with poor prognosis. Therefore, Foxp3 expressions in primary
      lesions as well as lymphogenic metastases appear to predict high-risk HSNCC
      patients. Novel therapeutic approaches targeting Foxp3+ cells might seem
      promising for this patient population.

PMID- 28741410
TI  - How can precision medicine be applied to temporomandibular disorders and its
      comorbidities?
AB  - The Eighth Scientific Meeting of The TMJ Association, Ltd. was held in Bethesda,
      Maryland, September 11-13, 2016. As in the past, the meeting was cosponsored by
      components of the National Institutes of Health with speakers invited to review
      the state of temporomandibular disorder science and propose recommendations to
      further progress. The theme of precision medicine, which aims to tailor disease
      treatment and prevention to match the characteristics of an individual patient
      (genetic, epigenetic, environmental, lifestyle) underscored the current consensus
      that temporomandibular disorders are no longer viewed as local conditions of jaw
      pain and dysfunction. Rather, they represent a complex family of biopsychosocial
      disorders that can progress to chronic pain, most often accompanied by one or
      more other chronic pain conditions. Temporomandibular disorders and these
      comorbidities, called chronic overlapping pain conditions, predominantly or
      exclusively affect women in their childbearing years and reflect central nervous
      system sensitization. Presenters at the meeting included leaders in
      temporomandibular disorder and pain research, temporomandibular disorder patients
      and advocates, and experts in other fields or in the use of technologies that
      could facilitate the development of precision medicine approaches in
      temporomandibular disorders.

PMID- 28741411
TI  - Intraoperative evaluation of the effects of femoral component offset and head
      size on joint stability in total hip arthroplasty.
AB  - PURPOSE: To evaluate intraoperatively the effects of femoral offset and head size
      on stability of the hip joints in total hip arthroplasty (THA) via posterior
      approach. METHODS: Thirty cementless THAs were included in this study. After
      acetabular shell and femoral broach fixation, trial reduction was repeated using
      a femoral neck (5- to 8-mm higher or standard offset) and a head (26 mm or 32
      mm). To evaluate joint stability, range of internal rotation (IR) in hip flexion
      prior to posterior subluxation and range of external rotation (ER) in hip
      extension were measured. RESULTS: The high-offset neck provided significantly
      (approximately 10 degrees ) greater range of IR to subluxation than the standard
      offset neck. No hips ended in anterior subluxation by ER. The head size did not
      have significant effects on the stability. CONCLUSION: Results suggest that the 5
      to 8-mm greater femoral offset might be effective in preventing instability in
      primary THA.

PMID- 28741412
TI  - Directly Induced Neural Differentiation of Human Adipose-Derived Stem Cells Using
      Three-Dimensional Culture System of Conductive Microwell with Electrical
      Stimulation.
AB  - Adipose-derived stem cells (ADSCs) have the capacity to differentiate into neural
      precursor cells which can be used for nerve regeneration. However, their
      inherently low neurogenic differentiation efficiency limits further clinical
      applications. This study was designed to promote neurogenic differentiation
      efficacy of ADSCs by integrating conductive hydrogel-based microwells with
      electrical stimulation (ES). We hypothesize that ADSCs will differentiate more
      efficiently into neural precursor cells when electrically stimulated in
      conductive hydrogel microwells. To make the conductive hydrogel-based microwell,
      polyethylene glycol (PEG) diacrylate aqueous solution mixed with poly(3,4
      ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) was patterned with the
      polydimethylsiloxane mold and exposed to UV light to induce photo-cross-linking
      of the conductive hydrogel. After seeding the ADSCs in the microwells, the cells
      formed distinct cell spheres in PEG microwells and wide disks in the
      PEG/PEDOT:PSS microwells. Although the microwells yielded varying three
      dimensional (3D) cell aggregate structure, cell viability was not affected. After
      neurogenic differentiation with ES, the ADSC aggregates in PEG/PEDOT:PSS
      microwells with ES expressed greater positive neuronal differentiation markers
      compared to nonstimulated PEG/PEDOT:PSS microwells. Although all neuronal gene
      expression levels were greater in PEG microwells with ES, the increased rates of
      gene expression levels between treated and untreated PEG/PEDOT:PSS microwells
      were much higher compared to PEG microwells. This would mean that electrically
      stimulating ADSC aggregates in conductive microwells is an effective method in
      increasing neurogenic differentiation. Therefore, we propose a most effective
      strategy taking advantage of a 3D conductive culture system which can be useful
      in a wide variety of electrical application.

PMID- 28741413
TI  - Modulating Children's Manual Preference Through Spontaneous Nondominant Hand Use.
AB  - We evaluated the effect of repeated use of the nonpreferred hand on young
      children's manual preference by positioning toys in the left hemifield in
      egocentric coordinates to induce right-handed 4-5-year-olds to use their left
      hands spontaneously. We induced motor activities in the laterally biased
      workspace by presenting tasks in a ludic context over different days, similar to
      their daily kindergarten experience. Preceding and following these lateralized
      experiences, the children were tested on a task requiring reaching, grasping, and
      inserting cards into a slot. In the 1-day retention assessment, we found that
      repeated use of the nonpreferred left hand in the previous phase led to increased
      use of the left hand to perform the probing task. Following 14 days of rest, the
      children with induced left-hand experiences used exclusively their left hands to
      manipulate the leftmost card positions. We propose that repeated use of the
      nonpreferred left hand leads to increased confidence to plan left-handed
      movements for subsequent tasks.

PMID- 28741414
TI  - The Decline of Laparoendoscopic Single-Site Surgery: A Survey of the
      Endourological Society to Identify Shortcomings and Guidance for Future
      Directions.
AB  - INTRODUCTION: To analyze the most recent temporal trends in the adoption of
      urologic laparoendoscopic single-site (LESS), to identify the perceived
      limitations associated with its decline, and to determine factors that might
      revive the role of LESS in the field of minimally invasive urologic surgery.
      MATERIALS AND METHODS: A 15 question survey was created and sent to members of
      the Endourological Society in September 2016. Only members who performed LESS
      procedures in practice were asked to respond. RESULTS: In total, 106 urologists
      responded to the survey. Most of the respondents were from the United States
      (35%) and worked in an academic hospital (84.9%). Standard LESS was the most
      popular approach (78.1%), while 14.3% used robotics, and 7.6% used both. 2009
      marked the most popular year to perform the initial (27.6%) and the majority
      (20%) of LESS procedures. The most common LESS procedure was a radical/simple
      nephrectomy (51%) followed by pyeloplasty (17.3%). In the past 12 months, 60% of
      respondents had performed no LESS procedures. Compared to conventional
      laparoscopy, respondents only believed cosmesis to be better, however, this
      enthusiasm waned over time. Worsening shifts in enthusiasm for LESS also occurred
      with patient desire, marketability, cost, safety, and robotic adaptability. The
      highest rated factor to help LESS regain popularity was a new robotic platform.
      CONCLUSION: The decline of LESS is apparent, with few urologists continuing to
      perform procedures attributed to multiple factors. The availability of a purpose
      built robotic platform and better instrumentation might translate into a renewed
      future interest of LESS.

PMID- 28741415
TI  - Gram-negative bacterial membrane vesicle release in response to the host
      environment: different threats, same trick?
AB  - Bacteria are confronted with a multitude of stressors when occupying niches
      within the host. These stressors originate from host defense mechanisms, other
      bacteria during niche competition or result from physiological challenges such as
      nutrient limitation. To counteract these stressors, bacteria have developed a
      stress-induced network to mount the adaptations required for survival. These
      stress-induced adaptations include the release of membrane vesicles from the
      bacterial envelope. Membrane vesicles can provide bacteria with a plethora of
      immediate and ultimate benefits for coping with environmental stressors. This
      review addresses how membrane vesicles aid Gram-negative bacteria to cope with
      host-associated stress factors, focusing on vesicle biogenesis and the
      physiological functions. As many of the pathways, that drive vesicle biogenesis,
      confer we propose that shedding of membrane vesicles by Gram-negative bacteria
      entails an integrated part of general stress responses.

PMID- 28741416
TI  - American Joint Committee on Cancer Eighth Edition Changes in Staging Criteria:
      Implications for Data Collection.
AB  - The American Joint Committee on Cancer, in the eighth edition of its cancer
      staging manual, makes a number of changes to improve survival predictions in
      human malignancy. In this commentary, we examine the national collection of data
      for head and neck cancer. We outline and review the major changes made in head
      and neck cancer staging, identify the key data elements that will need to be
      collected with the new edition's criteria, and discuss the institutional
      adjustments currently being made to data collection under the new guidelines to
      improve the quality of data in our national cancer databases.

PMID- 28741417
TI  - Syndemics of stigma, minority-stress, maladaptive coping, risk environments and
      littoral spaces among men who have sex with men using chemsex.
AB  - There has been a steep rise in the use of drugs during sex (chemsex) by some men
      who have sex with men in economically developed countries, with associated
      increases in sexual risk for HIV and other STIs. This paper presents data from
      telephone interviews with 15 men attending sexual health clinics for post
      exposure prophylaxis following a chemsex-related risk for HIV and discusses some
      of the theoretical approaches that have been employed to understand chemsex and
      inform interventions. Interviews were conducted as part of a larger intervention
      study, which used an adapted version of motivational Interviewing to explore risk
      behaviour and support change. Participants conceptualised their chemsex and HIV
      related risks in a psycho-social context, highlighting the influences of psycho
      socio-cultural challenges of homophobic marginalisation and the 'gay scene' on
      behaviour. Multiple influences of stigma, marginalisation, minority stress and
      maladaptive coping (including drug-use) contribute to syndemic 'risk
      environments' and 'littoral spaces' in which chemsex and risk behaviours are
      played out.

PMID- 28741418
TI  - Focal Adhesion Kinase Activation Is Necessary for Stretch-Induced Alignment and
      Enhanced Differentiation of Myogenic Precursor Cells.
AB  - Myogenic precursors sense and dynamically respond to mechanical stimulation
      through complex integrin-mediated mechanotransduction, in which focal adhesion
      kinase (FAK) is a fundamental intracellular signaling mediator. When skeletal
      myoblasts are exposed to uniaxial cyclic tensile strain (UCTS), they display
      uniform alignment and an enhanced rate of differentiation. In this work, we
      explored the role of FAK activation by using C2C12 myoblasts that were grown on
      flexible culture plates and exposed to UCTS during the early differentiation
      phase. After 24 h, the cells oriented perpendicularly to the direction of strain
      and exhibited an enhanced differentiation profile. Next, the cells were exposed
      to a strain field that was either kept in the same direction or rotated 90
      degrees , in the presence or not of an FAK phosphorylation inhibitor. On
      reorientation of the strain field by 90 degrees , the cells reassembled their
      focal adhesions and actin cytoskeleton to regain the perpendicular position with
      respect to the engaging stress. After blocking the FAK, however, the cells failed
      to respond to the reoriented strain field and their differentiation was
      abrogated. Interestingly, when the strain field remained in the same direction,
      the FAK inhibitor compromised the differentiation, even though there was no
      evident change in cell orientation. Our data indicate that during exposure to
      UCTS, the activation of FAK is necessary for the myoblasts to undergo alignment
      and enhanced differentiation.

PMID- 28741419
TI  - Measuring and diagnosing unilateral neglect: a standardized statistical
      procedure.
AB  - OBJECTIVE: Unilateral neglect is usually investigated by adminstering stimuli
      (targets) in different positions, with targets being responded to by the patient
      (Hit) or omitted. In spite of this homogeneity of data type, neglect indices and
      diagnostic criteria vary considerably, causing inconsistencies in both clinical
      and experimental settings. We aimed at deriving a standard analysis which would
      apply to all tasks sharing this data form. METHODS: A-priori theoretical
      reasoning demonstrated that the mean position of Hits in space (MPH) is an
      optimal index for correctly diagnosing and quantifying neglect. Crucially MPH
      eliminates the confounding effects of deficits that are different from neglect
      (non-lateral) but which decrease Hit rate. We ran a Monte Carlo study to assess
      MPH's (so far overlooked) statistical behavior as a function of numbers of
      targets and Hits. RESULTS: While average MPH was indeed insensitive to non
      lateral deficits, MPH's variance (like that of all other neglect indices)
      increased dramatically with increasing non-lateral deficits. This instability
      would lead to alarmingly high false-positive rates (FPRs) when applying a
      classical diagnostic procedure that compares one patient with a control sample.
      We solved the problem by developing an equation that takes into account MPH
      instability and provides correct cut-offs and close-to-nominal FPRs, even without
      control subjects. We developed a computerized program which, given the raw data,
      yields the MPH, a z-score and a p-value. CONCLUSIONS: We provided a standard
      method that allows clinical and experimental neuropsychologists to diagnose and
      measure neglect in a consistent way across the vast majority of tasks.

PMID- 28741420
TI  - Outreach syncope clinic managed by a nurse practitioner: Outcome and cost
      effectiveness.
AB  - Introduction The purpose of this study was to assess the clinical and financial
      outcomes of a novel outreach syncope clinic. Methods We compared the clinical
      outcome of the Faint and Fall Clinic at the American Center (January-June 2016)
      with that of the University of Wisconsin Health and Clinics Faint and Fall Clinic
      (January 2013-December 2014). The American Center-Faint and Fall Clinic is run
      solely by a nurse practitioner, assisted by online faint-decision software and
      consultancy of a faint specialist through video-conferencing. Results Five
      hundred and twenty-eight consecutive patients were seen at the University of
      Wisconsin Hospital and Clinics-Faint and Fall Clinic and 68 patients at the
      American Center-Faint and Fall Clinic. The patients' clinical characteristics
      were similar except for a lower age in the American Center patients (45 +/- 18 vs
      51 +/- 22, p = 0.03). Overall, a diagnosis was made within 45 days in 70% (95%
      confidence interval 66-74%) of the University of Wisconsin Hospital and Clinics
      patients and 69% (95% confidence interval 58-80%) of the American Center
      patients, ( p = 0.9). A mean of 3.0 +/- 1.6 tests per patient was used in the
      University of Wisconsin Hospital and Clinics group compared to 1.5 +/- 0.8 tests
      per patient in the American Center group, p = 0.001. Over the six-month study
      period, the total revenue at the American Center was US$152,597 (contribution
      margin of US$122,393 plus professional revenue of US$30,204). The total cost of
      the nurse practitioner including benefits was US$66,662 ((US$98,466 salary/year +
      35.4% benefits)/2). Total revenue minus expenses resulted in a net profit of
      US$85,935. Discussion A nurse practitioner-run outreach syncope-clinic equipped
      with online faint-decision software and consultancy of a faint specialist through
      vedio-conferencing is feasible and financially self-sustainable. It allows the
      dissemination of standardized high-quality syncope care to patients who have no
      immediate access to a tertiary teaching hospital.

PMID- 28741421
TI  - Joint dysfunction associated with venous malformations of the limbs: Which
      patients are at high risk?
AB  - Objectives Joint dysfunction occurs frequently in patients with venous
      malformations of the extremities. This study aims to describe the risk factors of
      joint dysfunction in these patients. Method We retrospectively collected clinical
      and radiological aspects of 168 patients with extremity venous malformations from
      January 2013 to August 2015. Patients were categorized into "with joint
      dysfunction" or "without joint dysfunction" groups according to the symptoms.
      Results Forty-four (26%) patients were assigned into with joint dysfunction
      group. Univariate analysis showed that the significant variables were age (P =
      0.008), location (P = 0.005), size (P < 0.001), involved tissue (P < 0.001),
      visual analogue scale scores of pain (P = 0.004), pain duration (P = 0.018), and
      therapy history (P < 0.001). Multivariate analysis showed that the factors
      associated with joint dysfunction were age below 10 years (adjusted odds ratio =
      2.70, P = 0.004), lower limb (adjusted odds ratio = 2.72, P = 0.042), pain
      duration over 1 year (adjusted odds ratio = 3.47, P = 0.001) and therapy history
      (yes) (adjusted odds ratio = 3.71, P = 0.004). Conclusion This study provides
      preliminary evidence indicating which patients are at high risk for joint
      dysfunction associated with limb venous malformations.

PMID- 28741422
TI  - Longitudinal study of hippocampal volumes in heavy cannabis users.
AB  - BACKGROUND: Cannabis exposure, particularly heavy cannabis use, has been
      associated with neuroanatomical alterations in regions rich with cannabinoid
      receptors such as the hippocampus in some but not in other (mainly cross
      sectional) studies. However, it remains unclear whether continued heavy cannabis
      use alters hippocampal volume, and whether an earlier age of onset and/or a
      higher dosage exacerbate these changes. METHODS: Twenty heavy cannabis users
      (mean age 21 years, range 18-24 years) and 23 matched non-cannabis using healthy
      controls were submitted to a comprehensive psychological assessment and magnetic
      resonance imaging scan at baseline and at follow-up (average of 39 months post
      baseline; standard deviation=2.4). Cannabis users started smoking around 16 years
      and smoked on average five days per week. A novel aspect of the current study is
      that hippocampal volume estimates were obtained from manual tracing the
      hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a
      previously validated protocol. RESULTS: Compared to controls, cannabis users did
      not show hippocampal volume alterations at either baseline or follow-up.
      Hippocampal volumes increased over time in both cannabis users and controls,
      following similar trajectories of increase. Cannabis dose and age of onset of
      cannabis use did not affect hippocampal volumes. CONCLUSIONS: Continued heavy
      cannabis use did not affect hippocampal neuroanatomical changes in early
      adulthood. This contrasts with prior evidence on alterations in this region in
      samples of older adult cannabis users. In young adults using cannabis at this
      level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.

PMID- 28741423
TI  - Cognitive control in young adults with cannabis use disorder: An event-related
      brain potential study.
AB  - Contemporary models of substance use disorders emphasize the role of cognitive
      control, which has been linked to difficulties in resisting the use of
      substances. In the present study, we measured two aspects of cognitive control,
      response inhibition (operationalized by a Go/NoGo Task) and performance
      monitoring (operationalized by an Eriksen Flanker Task), in a group of young
      cannabis-use disorder (CUD) patients and compared these functions with two
      control groups (i.e. a group of cigarette smokers and a group of non-smokers). We
      employed both behavioural and electrophysiological measures. The results indicate
      that CUD patients displayed reduced NoGo-P3 event-related potentials compared
      with non-smoking controls, but not compared with smoking controls. In addition,
      CUD patients were slower on Go trials than both control groups. No other between
      group electrophysiological or behavioural differences were observed. These
      results seem to suggest that CUD patients have problems related to response
      inhibition, but performance monitoring seems relatively unaffected.

PMID- 28741424
TI  - Validity of the Breakup Strategies Questionnaire in Korea: Exploratory Structural
      Equation Modeling and Rasch's Modeling.
AB  - This study examines the validity of the Korean implementation of the Breakup
      Strategies Questionnaire. In Study 1, the construct validity of the Breakup
      Strategies Questionnaire was explored with 292 Korean undergraduate students.
      Exploratory Structural Equation Modeling and Rasch's Modeling suggest 30 items
      with four factors (Avoidance/withdrawal, Positive tone/self-blame, Open
      confrontation, and Indirect manipulation) and five points in response. Study 2
      with 174 Korean undergraduate students suggested potential gender differences in
      breakup strategy dimensions and provided support for concurrent validity with a
      measure of personal styles of coping as well as discriminant validity with social
      desirability. Cultural implications for the use of breakup strategies are
      discussed.

PMID- 28741425
TI  - Gabapentin in the Management of Pain following Tonsillectomy: A Randomized Double
      Blind Placebo-Controlled Trial.
AB  - Objective To determine if a single dose of oral gabapentin given prior to
      tonsillectomy decreases postoperative morbidity. Study Design Prospective
      randomized double-blind placebo-controlled trial. Setting Southern District
      Health Board University Hospitals, New Zealand, over a 10-month period. Subjects
      and Methods Seventy-three adults undergoing tonsillectomy were randomized to
      receive either a single preoperative dose of oral gabapentin (600 mg) or placebo.
      A standard analgesic protocol was prescribed for 14 postoperative days. The
      primary outcome was a patient-assigned visual analog scale pain score during rest
      and swallow; secondary outcomes were analgesic consumption, nausea, vomiting, and
      return to normal diet and activities. Complications and adverse effects were also
      recorded. Results Thirty-seven participants were allocated to the placebo group
      and 36 to the gabapentin group. After withdrawals, data were analyzed from 31 in
      the placebo group and 27 in the gabapentin group. Pain scores between groups were
      not significantly different within the first 6 hours. The gabapentin group
      recorded significantly higher pain scores between days 5 and 10 (maximal
      difference, day 8: 17.6 mm; effect size, -8.87; P = .03; 95% CI, -16.883 to 
      0.865). There was no significant difference in swallow pain scores or early
      postoperative fentanyl consumption. Consumption of paracetamol ( P = .01 at day
      13 and P = .004 at day 14) and codeine ( P < .05 at days 3-5, 7, 8, 10, 14) was
      higher in the gabapentin group. No significant difference between groups was
      found for the other outcomes. Conclusions Preemptive gabapentin (600 mg) was
      associated with greater postoperative pain scores and analgesic consumption
      following adult tonsillectomy when compared with placebo.

PMID- 28741426
TI  - Influence of Different Irradiation Protocols on Vascularization and Bone
      Formation Parameters in Rat Femora.
AB  - Aim of the present study was the establishment of an efficient and reproducible
      model for irradiation of rat femora as a model for impaired osteogenesis and
      angiogenesis. Four different irradiation protocols were compared: single
      irradiation of the left femur with 20 Gy and explantation after 4 or 8 weeks
      (group A, B) and three irradiation fractions at 3-4 days intervals with 10 Gy and
      explantation after 4 or 8 weeks (group C, D). The contralateral, unirradiated
      femur served as control. Evaluation included histology, microcomputertomography
      (MUCT), and real-time polymerase chain reaction. Histology showed a pronounced
      increase of vacuoles in bone marrow after irradiation, especially after 4 weeks
      (group A and C), demonstrating bone marrow edema and fatty degeneration.
      Irradiation provoked a decrease of total cell numbers in cortical bone and of
      hypoxia-inducible factor 1 alpha (HIF1alpha)-positive cells in bone marrow. The
      expression of several markers (osteocalcin [OCN], runt-related transcription
      factor 2 [RUNX2], transforming growth factor beta 1 [TGFbeta1], tumor necrosis
      factor alpha [TNFalpha], vascular endothelial growth factor A [VEGFA], and
      HIF1alpha) was decreased in group A after irradiation. This might suggest a
      decreased metabolism after irradiation. A significant decrease in small-sized
      vessels was seen in MUCT evaluation in group A and D. Single irradiation with 20
      Gy had the most severe and reproducible impact on osteogenesis and angiogenesis
      after 4 weeks while being well tolerated by all animals, thus making it an
      excellent model for evaluation of bone healing and vascularization in irradiated
      tissue.

PMID- 28741427
TI  - Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Local Osteoporotic
      Canine Mandible Model for the Evaluation of Peri-Implant Bone Regeneration.
AB  - The canine mandible is useful for studying bone regeneration after dental implant
      placement. However, it is limited in investigations of peri-implant osteogenesis
      under osteoporotic conditions due to the insignificant osteoporotic effect of
      ovariectomy. This study aimed at establishing a local osteoporotic model without
      ovariectomy by using receptor activator of nuclear factor kappa-B ligand (RANKL)
      in a canine mandible model. This new model was used to evaluate the effects of
      injectable beta-tricalcium phosphate (TCP) microsphere bone grafts on peri
      implant bone regeneration under osteoporotic conditions with combinations of
      recombinant human bone morphogenetic protein-2 (rhBMP-2). A local osteoporotic
      canine mandible model was designed by creating a hole in the mandibular alveolar
      bone, then implanting a collagen sponge soaked with 20, 40, or 60 MUg RANKL into
      the hole, and leaving it for 2 weeks. After the establishment of the dose for
      maximum osteoporotic bone loss at 40 MUg of RANKL, the main surgery was
      performed. RANKL-soaked collagen sponges were removed, and dental implants were
      placed with bone grafts in five groups: implant only, TCP, and TCP + rhBMP-2 at
      5, 15, and 45 MUg. Peri-implant bone generation was determined by radiologic and
      histologic evaluations at 6 weeks after dental implant placement. On performing
      micro-computed tomography analysis, the group with TCP + 5 MUg rhBMP-2 showed the
      highest bone volume than the other groups and a 22% increase (p < 0.05) compared
      with the implant-only group. In the histologic analysis, the TCP-only and TCP + 5
      MUg BMP-2 groups showed higher bone areas (14% and 16% increase, respectively)
      and bone-implant contact (12% and 7% increase, respectively) compared with the
      implant-only group, but there was no significant difference among the groups. In
      this study, the RANKL-induced local osteoporotic canine mandible model was useful
      for peri-implant bone regeneration under osteoporotic conditions such as those
      found in geriatric patients. The injectable beta-TCP bone grafts used in this
      study were effective in peri-implant bone generation under osteoporotic
      conditions, and their efficiency was enhanced at 5 MUg BMP-2 compared with higher
      concentrations of BMP-2.

PMID- 28741428
TI  - Corrigendum.
AB  - Frankis J, Goodall L, Clutterbuck D, Abubakari A-R and Flowers P. Regular STI
      testing amongst men who have sex with men and use social media is suboptimal - a
      cross-sectional study. International Journal of STD & AIDS 2017; 28: 573-583.
      DOI: 10.1177/0956462416636780. Razak Abubakari would like to change the
      presentation of his name in the online version of this article to Abdul-Razak
      Abubakari.

PMID- 28741429
TI  - Rapid systemic delivery of zolmitriptan using an adhesive dermally applied
      microarray.
AB  - Adhesive Dermally-Applied Microarray (ADAM) is a device for intracutaneous drug
      administration consisting of a 3 cm2 disposable array of drug-coated titanium
      microprojections on an adhesive backing. It is applied using a low cost,
      reusable, handheld applicator. Microprojections penetrate the stratum corneum,
      delivering drug proximal to capillaries with limited likelihood of pain. The
      pharmacokinetics of zolmitriptan delivery using ADAM was evaluated in 20 healthy
      volunteers. Median tmax was <20 min, comparable to subcutaneous sumatriptan.
      Absorption was faster than for oral zolmitriptan, with higher exposure in the
      first 2 h. Most adverse events were consistent with those seen in previous
      triptan trials. Application site reactions were generally mild and resolved
      within 24 h. ADAM zolmitriptan shows a promising pharmacokinetic profile for
      migraine treatment.

PMID- 28741430
TI  - Orofacial neuropathic pain induced by oxaliplatin: downregulation of KCNQ2
      channels in V2 trigeminal ganglion neurons and treatment by the KCNQ2 channel
      potentiator retigabine.
AB  - Abstract: Neuropathic pain induced by chemotherapy drugs such as oxaliplatin is a
      dose-limiting side effect in cancer treatment. The mechanisms underlying
      chemotherapy-induced neuropathic pain are not fully understood. KCNQ2 channels
      are low-threshold voltage-gated K+ channels that play a role in controlling
      neuronal excitability. Downregulation of KCNQ2 channels has been proposed to be
      an underlying mechanism of sensory hypersensitivity that leads to neuropathic
      pain. However, it is currently unknown whether KCNQ channels may be downregulated
      by chemotherapy drugs in trigeminal ganglion neurons to contribute to the
      pathogenesis of chemotherapy-induced orofacial neuropathic pain. In the present
      study, mechanical sensitivity in orofacial regions is measured using the operant
      behavioral test in rats treated with oxaliplatin. Operant behaviors in these
      animals show the gradual development of orofacial neuropathic pain that manifests
      with orofacial mechanical allodynia. Immunostaining shows strong KCNQ2
      immunoreactivity in small-sized V2 trigeminal ganglion neurons in controls, and
      the numbers of KCNQ2 immunoreactivity positive V2 trigeminal ganglion neurons are
      significantly reduced in oxaliplatin-treated animals. Immunostaining is also
      performed in brainstem and shows strong KCNQ2 immunoreactivity at the trigeminal
      afferent central terminals innervating the caudal spinal trigeminal nucleus (Vc)
      in controls, but the KCNQ2 immunoreactivity intensity is significantly reduced in
      oxaliplatin-treated animals. We further show with the operant behavioral test
      that oxaliplatin-induced orofacial mechanical allodynia can be alleviated by the
      KCNQ2 potentiator retigabine. Taken together, these findings suggest that KCNQ2
      downregulation may be a cause of oxaliplatin-induced orofacial neuropathic pain
      and KCNQ2 potentiators may be useful for alleviating the neuropathic pain.

PMID- 28741431
TI  - Topical moringin-cream relieves neuropathic pain by suppression of inflammatory
      pathway and voltage-gated ion channels in murine model of multiple sclerosis.
AB  - Background: Neuropathic pain represents the major public health burden with a
      strong impact on quality life in multiple sclerosis patients. Although some
      advances have been obtained in the last years, the conventional therapies remain
      poorly effective. Thus, the discovery of innovative approaches to improve the
      outcomes for multiple sclerosis patients is a goal of primary importance. With
      this aim, we investigated the efficacy of the 4-(alpha-L
      rhamnopyranosyloxy)benzyl isothiocyanate (moringin), purified from Moringa
      oleifera seeds and ready-to-use as topical treatment in experimental autoimmune
      encephalomyelitis, murine model of multiple sclerosis. Female C57BL/6 mice
      immunized with myelin oligodendrocyte glycoprotein (MOG35-55) were topically
      treated with 2% moringin cream twice daily from the onset of the symptoms until
      the sacrifice occurred about 21 days after experimental autoimmune
      encephalomyelitis induction. Results: Our observations showed the efficacy of 2%
      moringin cream treatment in reducing clinical and histological disease score, as
      well as in alleviating neuropathic pain with consequent recovering of the hind
      limbs and response to mechanical stimuli. In particular, Western blot analysis
      and immunohistochemical evaluations revealed that 2% moringin cream was able to
      counteract the inflammatory cascade by reducing the production of pro
      inflammatory cytokines (interleukin-17 and interferon-gamma) and in parallel by
      increasing the expression of anti-inflammatory cytokine (interleukin-10).
      Interestingly, 2% moringin cream treatment was found to modulate the expression
      of voltage-gated ion channels (results focused on P2X7, Nav 1.7, Nav 1.8 KV4.2,
      and alpha2delta-1) as well as metabotropic glutamate receptors (mGluR5 and xCT)
      involved in neuropathic pain initiation and maintenance. Conclusions: Finally,
      our evidences suggest 2% moringin cream as a new pharmacological trend in the
      management of multiple sclerosis-induced neuropathic pain.

PMID- 28741432
TI  - Identification of interleukin-1 beta as a key mediator in the upregulation of
      Cav3.2-USP5 interactions in the pain pathway.
AB  - Abstract: We recently reported that nerve injury or peripheral inflammation
      triggers an upregulation of the deubiquitinase, USP5 in mouse dorsal root
      ganglion and spinal dorsal horn. This leads to dysregulated ubiquitination of
      Cav3.2 T-type calcium channels, thus increasing Cav3.2 channel plasma membrane
      expression and nociceptive signaling in the primary afferent pain pathway. This
      phenomenon could be recapitulated by noninvasive, optogenetic activation of
      transient receptor potential vanilloid-1-expressing nociceptors, indicating that
      neuronal activity is a key player in this process. Given the relevance of the pro
      inflammatory cytokine interleukin-1 beta in many forms of pathological pain, we
      hypothesized that interleukin-1 beta may be a critical cofactor required to drive
      upregulation of interactions between USP5 and Cav3.2 channels. Here, we report
      that gene expression, as well as protein levels for interleukin-1 beta and the
      endogenous interleukin-1 receptor-I antagonist, IL-1Ra are unaltered following
      conditioning stimulation of optogenetically targeted cutaneous nociceptors,
      indicating that neuronal activity is not a driver of interleukin-1 beta
      signaling. In contrast, co-immunoprecipitation experiments revealed that
      intrathecal administration of interleukin-1 beta in wild-type mice led to an
      increase in the interaction between USP5 and Cav3.2 in the spinal dorsal horn.
      Moreover, disruption of the interaction between USP5 and Cav3.2 with TAT peptides
      suppressed acute nocifensive responses produced by interleukin-1 beta, which was
      similar to that achieved by elimination of T-type channel activity with the
      channel blockers, mibefradil, or TTA-A2. Finally, this upregulation could be
      maintained in dorsal root ganglion neuron cultures exposed overnight to
      interleukin-1 beta, while the copresence of interleukin-1 receptor antagonist or
      the dampening of neuronal cell activity with tetrodotoxin attenuated this
      response. Altogether, our findings identify interleukin-1 beta as an upstream
      trigger for the upregulation of interactions between USP5 and Cav3.2 channels in
      the pain pathway, presumably by triggering increased firing activity in afferent
      fibers.

PMID- 28741433
TI  - Immune System Involvement in Specific Pain Conditions.
AB  - Abstract: Chronic pain is a significant problem worldwide and is the most common
      disability in the United States. It is well known that the immune system plays a
      critical role in the development and maintenance of many chronic pain conditions.
      The involvement of the immune system can be through the release of
      autoantibodies, in the case of rheumatoid arthritis, or via cytokines,
      chemokines, and other inflammatory mediators (i.e. substance P, histamine,
      bradykinin, tumor necrosis factor, interleukins, and prostaglandins). Immune
      cells, such as T cells, B cells and their antibodies, and microglia are clearly
      key players in immune-related pain. The purpose of this review is to briefly
      discuss the immune system involvement in pain and to outline how it relates to
      rheumatoid arthritis, osteoarthritis, fibromyalgia, complex regional pain
      syndrome, multiple sclerosis, and diabetic neuropathy. The immune system plays a
      major role in many debilitating chronic pain conditions and we believe that
      animal models of disease and their treatments should be more directly focused on
      these interactions.

PMID- 28741434
TI  - Robot-Applied Resistance Augments the Effects of Body Weight-Supported Treadmill
      Training on Stepping and Synaptic Plasticity in a Rodent Model of Spinal Cord
      Injury.
AB  - BACKGROUND: The application of resistive forces has been used during body weight
      supported treadmill training (BWSTT) to improve walking function after spinal
      cord injury (SCI). Whether this form of training actually augments the effects of
      BWSTT is not yet known. OBJECTIVE: To determine if robotic-applied resistance
      augments the effects of BWSTT using a controlled experimental design in a rodent
      model of SCI. METHODS: Spinally contused rats were treadmill trained using
      robotic resistance against horizontal (n = 9) or vertical (n = 8) hind limb
      movements. Hind limb stepping was tested before and after 6 weeks of training.
      Two control groups, one receiving standard training (ie, without resistance; n =
      9) and one untrained (n = 8), were also tested. At the terminal experiment, the
      spinal cords were prepared for immunohistochemical analysis of synaptophysin.
      RESULTS: Six weeks of training with horizontal resistance increased step length,
      whereas training with vertical resistance enhanced step height and movement
      velocity. None of these changes occurred in the group that received standard (ie,
      no resistance) training or in the untrained group. Only standard training
      increased the number of step cycles and shortened cycle period toward normal
      values. Synaptophysin expression in the ventral horn was highest in rats trained
      with horizontal resistance and in untrained rats and was positively correlated
      with step length. CONCLUSIONS: Adding robotic-applied resistance to BWSTT
      produced gains in locomotor function over BWSTT alone. The impact of resistive
      forces on spinal connections may depend on the nature of the resistive forces and
      the synaptic milieu that is present after SCI.

PMID- 28741435
TI  - Effect of Ankle Position and Noninvasive Distraction on Arthroscopic
      Accessibility of the Distal Tibial Plafond.
AB  - BACKGROUND: Osteochondral lesions of the tibial plafond (OLTPs) can lead to
      chronic ankle pain and disability. It is not known how limited ankle motion or
      joint distraction affects arthroscopic accessibility of these lesions. The
      purpose of this study was to determine the effects of different fixed flexion
      angles and distraction on accessibility of the distal tibial articular surface
      during anterior and posterior arthroscopy. METHODS: Fourteen below-knee cadaver
      specimens underwent anterior and posterior ankle arthroscopy using a 30-degree
      2.7-mm arthroscopic camera. Intra-articular working space was measured with a
      precision of 1 mm using sizing rods. The accessible areas at the plafond were
      marked under direct visualization at varying fixed ankle flexion positions.
      Arthroscopic accessibilities were normalized as percent area using a surface
      laser scan. Statistical analyses were performed to assess the relationship
      between preoperative ankle range of motion, amount of distraction, arthroscopic
      approach, and arthroscopic plafond visualization. RESULTS: There was
      significantly greater accessibility during posterior arthroscopy (73.5%) compared
      with anterior arthroscopy (51.2%) in the neutral ankle position ( P = .007).
      There was no difference in accessibility for anterior arthroscopy with increasing
      level of plantarflexion ( P > .05). Increasing dorsiflexion during posterior
      arthroscopy significantly reduced ankle accessibility ( P = .028). There was a
      significant increase in accessibility through the anterior and posterior approach
      with increasing amount of intra-articular working space (parameter estimates +/-
      SE): anterior = 14.2 +/- 3.34 ( P < .01) and posterior = 10.6 +/- 3.7 ( P < .05).
      Frequency data showed that the posterior third of the plafond was completely
      inaccessible in 33% of ankles during anterior arthroscopy. The frequency of
      inaccessible anterior plafond during posterior arthroscopy was 12%. CONCLUSION:
      Intra-articular working space and arthroscopic accessibility were greater during
      posterior arthroscopy compared with anterior arthroscopy. Improved accessibility
      of OLTPs may be achieved from posterior arthroscopy. Arthroscopic accessibility
      was heavily dependent on the amount of intraoperative joint working space
      achieved and not on ankle position. CLINICAL RELEVANCE: OLTPs are often
      encountered in tandem with talar lesions, and safely achieving intra-articular
      working space through noninvasive distraction greatly improved arthroscopic
      accessibility.

PMID- 28741436
TI  - Abstracts Presented at the SMART STROKES 2017 Conference, 10-11 August 2017, Gold
      Coast, QLD.

PMID- 28741437
TI  - Traumatic Brain Injury in a Community-Based Cohort of Homeless and Vulnerably
      Housed Individuals.
AB  - We characterized traumatic brain injury (TBI) and studied its associations with
      mental and physical health in a community cohort of homeless and vulnerably
      housed individuals. Detailed mental and physical health structured interviews,
      neuropsychological testing, and multimodal magnetic resonance imaging (MRI) were
      performed on 283 participants. Two TBI participant groups were defined for
      primary analyses: those with a self-reported history of TBI and those with MRI
      confirmation of TBI. By self-report, 174 participants (61.5%) reported a previous
      serious head or face injury (symptomatic or asymptomatic), with 100 (35.3%)
      experiencing symptoms consistent with TBI (any post-injury loss of consciousness,
      confusion, or memory loss). Persons self-reporting TBI had poorer current mental
      and physical health, more ongoing neurological symptoms, and a higher rate of
      mood disorders, compared to those with no TBI. The presence of a mood disorder, a
      TBI history, and an interaction between these factors contributed to lower mental
      health. There was evidence of TBI in 20 participants (6.9%) on clinical MRI
      sequences. These participants had globally lower cortical gray matter volumes and
      lower white matter fractional anisotropy (FA) values. Neurocognitive test scores
      positively correlated with both FA and cortical gray matter volumes in
      participants with MRI evidence of trauma. Previous TBI is associated with poorer
      mental and physical health in homeless and vulnerably housed individuals and
      interacts with mood disorders to exacerbate poor mental health. Focal traumatic
      lesions evident on MRI are associated with diffusely lower gray matter volumes
      and white matter integrity, which predict cognitive functioning.

PMID- 28741438
TI  - Bilateral Arteriovenous Shunts as a Method for Evaluating Tissue-Engineered
      Vascular Grafts in Large Animal Models.
AB  - There remains a need for large animal models to evaluate tissue-engineered
      vascular grafts (TEVGs) under arterial pressure to provide preclinical data for
      future potential human clinical trials. We present a comprehensive method for the
      interrogation of TEVGs, using an ovine bilateral arteriovenous (AV) shunt
      implantation model. Our results demonstrate that this method can be performed
      safely without complications, specifically acute heart failure, steal syndrome,
      and hypoxic brain injury, and it is a viable experimental paradigm. Our method
      allows for a non-invasive evaluation of TEVGs in terms of graft flow, graft
      diameter, and graft patency, while also allowing for graft needle puncture under
      ultrasound guidance. In addition, traditional pathological analysis, histology,
      and immunohistochemistry may be performed with the contralateral side providing
      paired control data to eliminate inter-subject variability while reducing the
      total number of animals. Further, we present a review of existing literature of
      preclinical evaluation of TEVGs in large animal models as AV conduits.

PMID- 28741439
TI  - Rudolf Ulrich Kronlein (1847-1910): An Innovative General, Thoracic, Neuro, and
      Ocular Surgeon.
AB  - The Swiss Professor Rudolf Ulrich Kronlein (1847-1910) was a pioneer in many
      fields of surgery, because he succeeded in introducing many innovations in
      different fields of surgery, for example, general surgery, thoracic surgery,
      neurosurgery, and ocular surgery. He was a reputable Professor of Surgery at
      Zurich University and was nominated for Nobel Prize in 1902.

PMID- 28741440
TI  - Commentary on Some Recent Theses Relevant to Combating Aging: August 2017.
AB  - Theses reviewed in this issue include "Engineering Cellular Input-Output for the
      Robust Control of Mammalian Cell-Based Therapies"; "Enzyme-Instructed Self
      Assembly (EISA) Selectively Targets Cancer Cells"; "Exploration of helminth
      derived immunoregulatory molecules as options for therapeutic intervention in
      allograft rejection and autoimmune disease"; "Expression of the Medial HOXA genes
      is indispensible for self-renewal in human hematopoietic stem cells"; "Gamma
      frequency entrainment attenuates amyloid load and modifies microglia"; and
      "Heterogeneous Distribution of Microvascular Blood Flow Contributes to Impaired
      Skeletal Muscle Oxygenation in Diabetes".

PMID- 28741441
TI  - Atmospheric Pressure and Abdominal Aortic Aneurysm Rupture: Results From a Time
      Series Analysis and Case-Crossover Study.
AB  - BACKGROUND: Associations between atmospheric pressure and abdominal aortic
      aneurysm (AAA) rupture risk have been reported, but empirical evidence is
      inconclusive and largely derived from studies that did not account for possible
      nonlinearity, seasonality, and confounding by temperature. METHODS: Associations
      between atmospheric pressure and AAA rupture risk were investigated using local
      meteorological data and a case series of 358 patients admitted to hospital for
      ruptured AAA during the study period, January 2002 to December 2012. Two analyses
      were performed-a time series analysis and a case-crossover study. RESULTS:
      Results from the 2 analyses were similar; neither the time series analysis nor
      the case-crossover study showed a significant association between atmospheric
      pressure ( P = .627 and P = .625, respectively, for mean daily atmospheric
      pressure) or atmospheric pressure variation ( P = .464 and P = .816,
      respectively, for 24-hour change in mean daily atmospheric pressure) and AAA
      rupture risk. CONCLUSION: This study failed to support claims that atmospheric
      pressure causally affects AAA rupture risk. In interpreting our results, one
      should be aware that the range of atmospheric pressure observed in this study is
      not representative of the atmospheric pressure to which patients with AAA may be
      exposed, for example, during air travel or travel to high altitudes in the
      mountains. Making firm claims regarding these conditions in relation to AAA
      rupture risk is difficult at best. Furthermore, despite the fact that we used one
      of the largest case series to date to investigate the effect of atmospheric
      pressure on AAA rupture risk, it is possible that this study is simply too small
      to demonstrate a causal link.

PMID- 28741442
TI  - A Systematic Review of the Methods of Diagnostic Accuracy Studies of the Afirma
      Gene Expression Classifier.
AB  - BACKGROUND: The Afirma(r) Gene Expression Classifier (GEC) risk stratifies The
      Bethesda System for the Reporting of Thyroid Cytopathology class III/IV
      (indeterminate) thyroid nodules (ITNs) as suspicious for malignancy or benign.
      Several authors have published studies describing the diagnostic accuracy of the
      GEC. However, the quality of these methods has not been rigorously examined.
      SUMMARY: In this study, MEDLINE and EMBASE were searched for studies published
      between January 1, 2010, and June 30, 2016, examining the sensitivity,
      specificity, negative predictive value, and positive predictive value of the GEC.
      The Quality of Diagnostic Accuracy Studies 2 was customized to evaluate the
      methods of included studies in each of four domains: nodule selection, index test
      execution, reference standard assignment, and flow and timing. Signaling
      questions were used to identify sources of potential bias in calculation of
      diagnostic accuracy, and issues of applicability were assessed. Three panelists
      applied the Quality of Diagnostic Accuracy Studies 2 tool to each study included,
      and divergence was resolved in conference. In 12 studies evaluated, the most
      common methodologic flaw was lack of reference standard diagnosis assignment to
      un-excised GEC-benign ITNs. Exclusion of these ITNs from the analyses resulted in
      unreliable estimates of specificity and negative predictive value. Other flaws
      identified included restriction to ITNs that had already been selected for
      referral for thyroidectomy or lobectomy. CONCLUSIONS: Future studies should
      define and assign a "true negative" label to GEC-benign nodules that do not
      develop malignant signs or symptoms during a pre-specified period of follow-up,
      and these nodules should be included in calculations of diagnostic accuracy.

PMID- 28741443
TI  - Stabilizing family life after gastric bypass surgery.
AB  - Weight-loss surgery requires lifelong lifestyle modifications for the maintenance
      of weight loss and health effects, and can affect both the individual and family.
      Earlier research indicates that the quality of social relationships has positive
      and negative influences on wellbeing and health. There is little research on
      family-life after a member has undergone gastric bypass (GBP) against obesity.
      Thus, this study aimed to develop a classic grounded theory about families with a
      member treated with GBP against obesity. The study design used classic grounded
      theory and included data from 16 interviews. Families' shared a main concern of
      unexpected changes after GBP, resulting in the theory Stabilizing family life,
      explained as a social process to decrease uncertainty and find stability and well
      being in family interactions. The social process develops differently which
      entail families: attaining unity, returning to old patterns, or disconnecting to
      find stability, depending on the discrepancy in expectations and knowledge. This
      is affected by the overall life situation, life-stage and relationship quality.
      The theory highlights unexpected change as a potential challenge for the family,
      as well as how they resolve this. Hence, the theory can be applied in care
      strategies for families. Identification of families needing support to stabilize
      family life after GBP requires further research.

PMID- 28741444
TI  - Mild pulmonary emphysema a risk factor for interstitial lung disease when using
      cetuximab for squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Interstitial lung disease (ILD) is an occasionally fatal adverse
      event associated with cetuximab (Cmab) therapy. Our objective was to clarify to
      what degree pulmonary emphysema is a risk factor in the treatment of head and
      neck cancer with Cmab through a retrospective analysis. METHODS: Subjects were
      116 patients who were administered Cmab for head and neck squamous cell
      carcinoma. The degree of pulmonary emphysema before initiating treatment with
      Cmab was visually assessed retrospectively, with scoring according to the Goddard
      classification used in Japanese chronic obstructive pulmonary disease (COPD)
      guidelines for chest computed tomography (CT). Scoring was conducted by two
      diagnostic radiologists and mean scores were used. Cutoffs for the development
      and nondevelopment of ILD were examined by receiver operating characteristic
      (ROC) analysis and Fisher's exact test. Values of p < .05 were considered to
      indicate a significant difference. RESULTS: Among the 116 patients, 11 (9.5%)
      developed ILD, and 105 (90.5%) did not. In ROC analysis, the optimal Goddard
      score cut-off of <3.0 offered 55% sensitivity and 81% specificity (p = .015).
      With a cutoff of <3.0, even very mild pulmonary emphysema would represent a risk
      factor for ILD when using Cmab.

PMID- 28741445
TI  - Results of endoscopic cartilage tympanoplasty procedure with limited
      tympanomeatal flap incision.
AB  - OBJECTIVE: The aim of this study was to evaluate the outcomes of this minimally
      invasive tympanomeatal incision technique performed during endoscopic transcanal
      cartilage tympanoplasty. STUDY DESIGN: Prospective clinical study. METHODS:
      Eighty-seven patients (87 ears) who had TM perforation with noncomplicated COM
      were included. All of the patients were operated with the endoscopic transcanal
      cartilage tympanoplasty technique. All of the data were prospectively collected.
      These included demographic data, date of the surgery, preoperative and
      postoperative pure-tone audiometry (PTA), localization of TM perforation and
      graft healing success. RESULTS: Mean follow-up time was 14.76 +/- 4.32 months.
      Graft-healing rate was 100%. Mean air bone gap level improvement (dB HL) at 0.5,
      1, 2 and 4 kHz were 13.87 +/- 7.30 dB HL, 9.09 +/- 7.59 dB HL, 9.74 +/- 6.40 dB
      HL and 7.46 +/- 6.37 dB HL, respectively. At all frequencies, there was
      significant difference between pre and postoperative mean air bone gap levels (p
      < .05). There was no significant correlation between the postoperative mean air
      bone gap level improvement and the localization of the perforation (p > .05).
      CONCLUSIONS: Endoscopic ear surgery has successful surgical outcomes with low
      complication rates. In this study, the outcomes of limited tympanomeatal flap
      incision was discussed. It is suggested that this technique is reliable with good
      hearing results with low postoperative complications rates.

PMID- 28741446
TI  - Uncovering the unknown: A grounded theory study exploring the impact of self
      awareness on the culture of feedback in residency education.
AB  - AIM: Self-assessment and reflection are essential for meaningful feedback. We
      aimed to explore whether the well-known Johari window model of self-awareness
      could guide feedback conversations between faculty and residents and enhance the
      institutional feedback culture. METHODS: We had previously explored perceptions
      of residents and faculty regarding sociocultural factors impacting feedback. We
      re-analyzed data targeting themes related to self-assessment, reflection,
      feedback seeking and acceptance, aiming to generate individual and institutional
      feedback strategies applicable to each quadrant of the window. RESULTS: We
      identified the following themes for each quadrant: (1) Behaviors known to self
      and others - Validating the known; (2) Behaviors unknown to self but known to
      others - Accepting the blind; (3) Behaviors known to self and unknown to others -
      Disclosure of hidden; and (4) Behaviors unknown to self and others - Uncovering
      the unknown. Normalizing self-disclosure of limitations, encouraging feedback
      seeking, training in nonjudgmental feedback and providing opportunities for
      longitudinal relationships could promote self-awareness, ultimately expanding the
      "open" quadrant of the Johari window. CONCLUSIONS: The Johari window, a model of
      self-awareness in interpersonal communications, could provide a robust framework
      for individuals to improve their feedback conversations and institutions to
      design feedback initiatives that enhance its quality and impact.

PMID- 28741447
TI  - Single Nucleotide Polymorphism in the COL11A2 Gene Associated with Heat Pain
      Sensitivity in Knee Osteoarthritis.
AB  - Abstract: Pain is one of the most prominent symptoms of osteoarthritis. However,
      there is often discordance between the pain experienced by individuals with
      osteoarthritis and the degree of articular pathology. This suggests that
      individual differences, including genetic variability in the central processing
      of nociceptive stimuli, may impact the presentation of osteoarthritis. Here, we
      show that the single nucleotide polymorphism rs16868943 in the collagen gene
      COL11A2 is significantly associated with lowered heat pain tolerance on the arm
      in participants with knee osteoarthritis (P = 1.21 * 10-6, P = 0.0053 after
      Bonferroni correction, beta = -3.42). A total of 161 knee osteoarthritis
      participants were included and evaluated for heat, punctate and pressure pain
      sensitivity of the affected knee and the ipsilateral arm. Each participant was
      genotyped for 4392 single nucleotide polymorphisms in genes implicated in pain
      perception, inflammation and mood and tested for association with pain
      sensitivity. The minor A allele of single nucleotide polymorphism rs16868943 was
      significantly associated with lower arm heat pain tolerance after correction for
      age, gender, race, and study site. This single nucleotide polymorphism was also
      nominally associated with other measures of heat pain sensitivity, including
      lowered knee heat pain tolerance (P = 1.14 * 10-5, P = 0.05 after Bonferroni
      correction), lowered arm heat pain threshold (P = 0.0039, uncorrected) and
      lowered knee heat pain threshold (P = 0.003, uncorrected). Addition of genotypes
      from 91 participants without knee pain produced a significant interaction between
      knee osteoarthritis status and the rs16868943 single nucleotide polymorphism in
      heat pain tolerance (P = 1.71 * 10-5), such that rs16868943 was not associated
      with heat pain tolerance in participants without knee pain (P = 0.12, beta =
      1.3). This is the first study to show genetic association with heat pain
      tolerance in individuals with osteoarthritis. The association is specific to
      participants who have already developed knee osteoarthritis, suggesting that the
      COL11A2 gene, which has previously been associated with familial osteoarthritis,
      may play a role in pain sensitization after the development of osteoarthritis.

PMID- 28741448
TI  - The Burden and Visit Prevalence of Pediatric Chronic Rhinosinusitis.
AB  - Objectives Pediatric chronic rhinosinusitis has a substantial impact, but its
      epidemiology has yet to be elucidated. Our objectives were (1) to determine the
      associated national visit burden and (2) to assess its frequency relative to
      other frequent childhood otolaryngological illnesses. Study Design Analysis of
      national survey databases. Setting Ambulatory care settings in the United States,
      2005 to 2012. Subjects and Methods Cases with a diagnosis of chronic
      rhinosinusitis were assessed in total and as a proportion of all visits reported
      in National Ambulatory Medical Care Surveys. To place these data into context,
      results for acute rhinosinusitis, allergic rhinitis, upper respiratory tract
      infection, and otitis media were also extracted and compared. Data specific to
      individual age group and calendar year were assessed. Results Chronic
      rhinosinusitis accounted for 5.6 million visits per annum (range, 3.7-7.5
      million) among patients 0 to 20 years of age. Children in the >5- to 10-year-old
      and >10- to 15-year-old age groups were more likely to be affected ( P < .001).
      Among all visits, chronic rhinosinusitis was diagnosed in 2.1% (95% confidence
      interval [CI], 1.9%-2.4%), acute rhinosinusitis in 0.6% (95% CI, 0.5%-0.7%),
      allergic rhinitis in 2.6% (95% CI, 2.3%-2.8%), upper respiratory tract infection
      in 8.0% (95% CI, 7.5%-8.4%), and otitis media in 6.7% (95% CI, 6.5%-7.1%).
      Chronic rhinosinusitis visits were significantly more prevalent than for acute
      rhinosinusitis (relative risk, 3.40; 95% CI, 2.70-4.10; P < .0001). Among those
      >15 to 20 years of age, chronic rhinosinusitis was 2.18-fold (95% CI, 1.65-2.70)
      more frequently diagnosed than otitis media. Conclusions The visit burden from
      pediatric chronic rhinosinusitis exceeds that of acute rhinosinusitis and equals
      the burden from allergic rhinitis.

PMID- 28741450
TI  - A Systematic Review of the Impact of Healthcare Reforms on Access to Emergency
      Department and Elective Surgery Services: 1994-2014.
AB  - This systematic review sought to identify whether health care reforms led to
      improvement in the emergency department (ED) length of stay (LOS) and elective
      surgery (ES) access in Australia, Canada, New Zealand, and the United Kingdom.
      The review was registered in the PROSPERO database (CRD42015016343), and nine
      databases were searched for peer-reviewed, English-language reports published
      between 1994 and 2014. We also searched relevant "grey" literature and websites.
      Included studies were checked for cited and citing papers. Primary studies
      corresponding to national and provincial ED and ES reforms in the four countries
      were considered. Only studies from Australia and the United Kingdom were
      eventually included, as no studies from the other two countries met the inclusion
      criteria. The reviewers involved in the study extracted the data independently
      using standardized forms. Studies were assessed for quality, and a narrative
      synthesis approach was taken to analyze the extracted data. The introduction of
      health care reforms in the form of time-based ED and ES targets led to
      improvement in ED LOS and ES access. However, the introduction of targets
      resulted in unintended consequences, such as increased pressure on clinicians
      and, in certain instances, manipulation of performance data.

PMID- 28741451
TI  - Perceived neighborhood environmental characteristics and different types of
      physical activity among Brazilian adolescents.
AB  - Little is known about the association between environmental characteristics and
      types of physical activity in adolescents in a Latin American context. The aim of
      this study was to examine the association between perceived neighborhood
      environmental characteristics and different types of physical activity in 2,874
      adolescents from Joao Pessoa, Paraiba State, Northeastern Brazil. The types of
      activity measured by questionnaire (>=10 min/day) included sports, physical
      exercises, active commuting and recreational activities. Neighborhood
      characteristics were measured by a 15-item scale. Multilevel analyses showed that
      adolescents who reported "having places they liked to go to" (OR = 1.41; 95%CI:
      1.10-1.79) and "places with opportunities to practice" (OR = 1.29; 95%CI: 1.01
      1.65) were more likely to play sports. "Seeing interesting things while walking"
      (OR = 1.24; 95%CI: 1.01-1.53) and "Seeing other adolescents engaged in physical
      activity" (OR = 1.47; 95%CI: 1,05-2,06) were associated with exercises. "Seeing
      other adolescents engaged in physical activity" (OR = 1.47; 95%CI: 1.18-1.82),
      "the neighborhood is not violent" (OR = 1.29; 95%CI: 1.04-1.60) and "having
      places they like to go to" (OR = 1.59; 95%CI: 1.13-2.25) were positively
      associated and "places with opportunities to practice" (OR = 0.79; 95%CI: 0.63
      0.98) inversely related to active commuting. "Seeing other adolescents engaged in
      physical activities" (OR = 1.31; 95%CI: 1.05-1.63) and "seeing interesting things
      while walking" (OR = 1.26; 95%CI: 1.02-1.56) were associated with recreational
      activities. Neighborhood environmental characteristics associated with the
      physical activity vary with the type of practices adopted by adolescents.

PMID- 28741452
TI  - Young Age and Male Sex Are Predictors of Large-Volume Central Neck Lymph Node
      Metastasis in Clinical N0 Papillary Thyroid Microcarcinomas.
AB  - BACKGROUND: Large-volume lymph node metastasis (LNM) is associated with poor
      clinical outcomes in papillary thyroid microcarcinoma (PTMC) patients. However,
      sensitivity in the detection of central neck LNM on preoperative neck
      ultrasonography (US) is believed to be low. The aim of this study is to
      investigate the preoperative clinical factors associated with large-volume LNM in
      clinical N0 PTMC patients. METHODS: In all, 2329 clinical N0 PTMC patients who
      underwent total thyroidectomy with prophylactic central lymph node (LN)
      dissection were evaluated. The LNM status of these patients was divided into
      three groups by the number of metastatic nodes: no LNM, small-volume LNM (<=5
      metastatic LNs), and large-volume LNM (>5 metastatic LNs). The correlations
      between age, sex, and other clinical factors and large-volume LNM were evaluated.
      RESULTS: Large-volume LNM was found in 94 (4.0%) patients. Young (<40 years old)
      and male patients tended to have large-volume LNM (p for trend <0.001). Young age
      (odds ratio [OR] = 2.69 [confidence interval (CI) 1.64-4.32], p < 0.001) and male
      sex (OR = 5.79 [CI 3.67-9.10], p < 0.001) were independent risk factors for large
      volume LNM in multivariate analyses. The prevalence of large-volume LNM ranged
      from 24% in male patients <40 years of age to only 2% in female patients aged
      >=40 years. Multifocal tumors and presence of extrathyroidal extension were also
      considered risk factors for large-volume LNM. CONCLUSIONS: Large-volume LNM was
      more frequently found in young (<40 years) and male patients. These findings
      support the notion that surgery rather than observation may be favored in young
      and male clinically LN negative PTMC patients as a primary therapeutic option.

PMID- 28741453
TI  - No Effect of Levothyroxine and Levothyroxine-Induced Subclinical Thyrotoxicosis
      on the Pharmacokinetics of Sorafenib in Healthy Male Subjects.
AB  - BACKGROUND: Patients receiving the multikinase inhibitor sorafenib for locally
      recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC)
      refractory to radioactive iodine often receive concomitant levothyroxine for
      thyrotropin (TSH) suppression. In the Phase 3 DTC trial (DECISION), sorafenib
      exposure was approximately twofold higher than that observed in other cancers.
      This study assessed sorafenib pharmacokinetics without and with concomitant
      levothyroxine to examine whether a levothyroxine interaction or levothyroxine
      induced subclinical thyrotoxicosis results in increased sorafenib exposure in
      patients with DTC. METHODS: This was an open-label, two-period sequential
      treatment study in healthy male subjects. In period 1, day 1, subjects received a
      single oral dose of sorafenib 400 mg, followed by a minimal 10-day washout. In
      period 2, day 1, levothyroxine 300 MUg was administered orally once daily (q.d.)
      for 14 days. After 10 days, a single oral concomitant dose of sorafenib 400 mg
      was given. Blood samples for sorafenib pharmacokinetic analyses were obtained pre
      dose and at time points up to 96 hours after sorafenib dosing. Samples for
      thyroid tests were collected before and after levothyroxine dosing. RESULTS:
      Twenty-five subjects completed the study and were evaluable for pharmacokinetic
      analysis. Levothyroxine 300 MUg q.d. was well tolerated and induced subclinical
      thyrotoxicosis, producing full suppression of TSH (M +/- SD = 0.032 +/- 0.027
      mIU/L) and increased free thyroxine (from 0.94 +/- 0.09 to 1.77 +/- 0.33 ng/dL)
      and free triiodothyronine (from 2.87 +/- 0.28 to 4.24 +/- 0.66 pg/mL) levels by
      day 11 of period 2. The geometric mean (%CV) sorafenib maximum concentration
      (Cmax) without and with levothyroxine was 2.09 (68.1) and 1.78 (63.9) mg/L,
      respectively, with a corresponding geometric mean area under the curve of 68.1
      (68.2) and 64.3 (66.3) mg.h/L. Median (range) time to Cmax was 4.00 (2.98-16.0)
      and 4.02 (1.98-36.0) hours, respectively. Mean (%CV) half-life was 24.0 (25.3)
      and 25.7 (21.0) hours. All study drug-related adverse events were mild and
      included headache and fatigue for sorafenib, and headache, increased alanine
      aminotransferase and glutamate dehydrogenase, fatigue, and nervousness for
      levothyroxine. CONCLUSIONS: Levothyroxine 300 MUg q.d. for 14 days was well
      tolerated, induced subclinical thyrotoxicosis, and did not affect sorafenib
      pharmacokinetics. The findings suggest that concomitant use of levothyroxine with
      sorafenib is not likely responsible for the previously reported increase in
      sorafenib exposure in patients with DTC. However, the possible effects of long
      term levothyroxine dosing were not assessed.

PMID- 28741454
TI  - Nanovesicular Formulations for Cancer Gene Therapy.
AB  - In the last decades, gene therapy has become a novel therapeutic strategy for
      cancer treatment, including immunologic and molecular approaches. Among molecular
      avenue, the design of efficient and effective gene delivery systems, like
      cationic liposomes and niosomes, has been widely investigated and proposed as the
      most promising research area. The advantages of cationic vesicles rely on their
      natural ability to form complexes with anionic genetic molecules and deliver them
      into the cells via the endosomal pathway. Obviously, cationic vesicles- mediated
      gene delivery is affected by numerous factors, in particular composition, that
      strongly affects vesicle physical-chemistry characteristics and transfection
      effectiveness. This review will analyse the potential of cationic nanocarriers in
      cancer gene therapy, focusing on the role of liposomes and niosomes as vesicular
      devices and giving an exhaustive collection of the most representative
      investigations.

PMID- 28741455
TI  - Pivotal Roles of Interleukin-17 as the Epicenter of Bone Loss Diseases.
AB  - Bone remodelling is a strictly regulated dynamic process between bone resorption
      and bone formation. Many factors are involved in the process and affect the
      dynamic balance. Inflammation-mediated bone loss is a major feature of various
      bone diseases, including periodontitis, rheumatoid arthritis (RA) and
      spondyloarthritis (SpA). Interleukin-17 (IL-17) plays an important role in
      inflammatory bone disease and could be an attractive therapeutic target. This
      review focuses on the osteoclastic effects of IL-17 in different cell types and
      summarizes the current knowledge of IL-17 signalling pathways. Typical IL-17
      mediated bone destruction disorders are examined. The review also provides an
      overview of possible strategies for therapeutic intervention for inflammatory
      loss of bone targeting IL-17.

PMID- 28741456
TI  - Effects of Oral and Non-Insulin Injectable Antidiabetic Treatment in
      Hypertension: A Systematic Review.
AB  - BACKGROUND: Diabetes mellitus type 2 (T2DM) often co-exists with hypertension,
      and this aggregation of co-morbidities amplifies the risk for future
      cardiovascular events. Therefore, it appears crucial to understand the essence of
      choosing oral and non-insulin injectable anti-diabetic drugs (ADs) with a
      favorable hemodynamic impact that could partially attenuate the increased
      baseline cardiovascular risk. OBJECTIVE: We sought to evaluate the effect of ADs
      on blood pressure (BP) indices and to assess the potential role of certain ADs
      towards hypertension treatment. METHOD: We performed a systematic review of the
      literature searching MEDLINE via Pubmed for all human studies implementing ADs,
      either individually or in combinations. RESULTS: Metformin was found to reduce BP
      in small cohorts but failed to confirm its beneficial effect in a metaanalysis of
      41 studies. Thiazolidinediones are associated with BP lowering but are
      contraindicated in patients with heart failure. Sulfonylureas, on the other hand,
      may increase BP, while a-glucosidase inhibitors, DPP-4 inhibitors, and SGLT2
      inhibitors activate favorable pathophysiologic mechanisms serving as potential BP
      lowering agents. Relevant BP reduction was established for GLP-1 Ras in most
      clinical trials. CONCLUSION: The favorable hemodynamic impact of certain classes
      of ADs might provide synergistic or incremental therapeutic benefits in high-risk
      patients suffering from both T2DM and hypertension. Additional randomized trials
      designed under the hypothesis of the emerging beneficial hemodynamic effect of
      ADs are expected to provide more robust evidence and to guide the optimization of
      combined treatment strategies in this challenging group of patients.

PMID- 28741457
TI  - Anthocyanins: Multi-Target Agents for Prevention and Therapy of Chronic Diseases.
AB  - Anthocyanins, a flavonoid class of polyphenols, are water soluble dark colored
      natural pigments found in fruits and vegetables. Owing to their wide distribution
      in plant materials, dietary consumption of anthocyanins is high compared to other
      flavonoids. Anthocyanins, due to their multifaceted medicinal properties are the
      active components in many herbal folk medicines. As in vitro and in vivo results,
      animal models, and clinical trials in various cell lines suggest, anthocyanins
      possess antioxidant, antidiabetic, antihyperlipidemic, anti-inflammatory,
      anticarcinogenic, antiulcer, and preventive activities against cardiovascular
      diseases. Additionally, anthocyanins exhibit chemotherapeutic, cardioprotective,
      hepatoprotective, and neuroprotective activities. In the diet, anthocyanins are
      absorbed in the stomach and intestinal cells and rapidly detected in the plasma.
      These promising properties of anthocyanins may well provide health benefits
      against chronic diseases.

PMID- 28741458
TI  - Hybrid Polymeric-Magnetic Nanoparticles in Cancer Treatments.
AB  - Over the last years, magnetic nanoparticles have received a great attention in
      cancer therapy and diagnosis. Magnetic drug targeting, is a particularly
      promising application in this area as the nanoparticles can be directed to the
      tumor by external magnetic field and concentrated the drug in this tumor tissue.
      In addition to this magnetic targeting, their inherent magnetic properties
      provide sensitive contrast enhancement in magnetic resonance imaging (MRI) and
      can, therefore, be visualized and used for theranostic purposes. Another
      important pillar of cancer therapy in which magnetic nanoparticles can be
      successfully employed is the hyperthermia induced either magnetically or by
      infrared irradiation. In addition, recent works have suggested that magnetic
      nanoparticles can be used for mechanical stimulation of cells affecting their
      viability. Most of these applications require modification of the physiochemical
      and surface properties of the magnetic nanoparticles to control their
      biodistribution, toxicity and pharmacokinetics. In relation to this, polymer
      coatings are probably the preference alternative to cover the magnetic
      nanoparticles for cancer treatment applications. In this review, we attempt to
      provide an overview of the recent advances in the development and applications of
      polymeric magnetic nanoparticles in cancer treatment and diagnosis including MRI,
      drug delivery, magnetic hyperthermia, photothermia and magnetolysis.

PMID- 28741459
TI  - Discovery and Biochemical Characterization of a Thermostable Glucose-1-phosphate
      Nucleotidyltransferase from Thermodesulfatator indicus.
AB  - BACKGROUND: The biosynthesis of NDP-glucoses is based on the nucleotide transfer
      from NTP donor substrates to glucose-1-phosphates catalyzed by glucose-1
      phosphate nucleotidyltransferases. OBJECTIVES: The cloning and biochemical
      characterization of a glucose-1-phosphate nucleotidyltransferase (TiGPNT) from
      the deep sea bacterium Thermodesulfatator indicus. METHODS: The biochemical
      parameters of recombinant TiGPNT were determined using a plate reader-based
      coupled enzymatic assay, in which the reaction product UDP-glucose is oxidized in
      the presence of NAD+ forming UDP-Glucuronic acid and NADH. The substrate
      promiscuity of the enzyme was determined using thin-layer chromatography and
      MALDI-ToF mass spectrometry. RESULTS: TiGPNT was recombinantly expressed under
      the control of the T7 promoter in Escherichia coli and could be successfully
      enriched by heat treatment at 80 degrees C for 30 min. The obtained enzyme worked
      best at pH 7.5 and the optimum reaction temperature was determined to be 50
      degrees C. Interestingly, TiGPNT could fully retain its activity even after
      extended incubation periods at temperatures of up to 80 degrees C. The enzyme was
      strongly inhibited in the presence of Cu2+ and Fe2+ ions and EDTA. Among the
      tested glycosyl donor substrates, TiGPNT showed strict specificity towards
      glucose-1-phosphate. At the same time, TiGPNT was highly promiscuous towards all
      tested nucleotide donor substrates. CONCLUSION: TiGPNT shows comparable
      biochemical features in regards to pH optima, temperature optima and the
      substrate specificity to characterized glucose-1-phosphate nucleotidyltransferase
      from other species. The enzyme was capable of utilizing glucose-1-phosphate and
      all tested nucleoside triphosphate donors as substrates. The high activity of the
      enzyme and the simple purification protocol make TiGPNT an interesting new
      biocatalyst for the synthesis of glucose-diphospho nucleosides.

PMID- 28741460
TI  - Discovery and Biochemical Characterization of UDP-Glucose Dehydrogenase from
      Akkermansia muciniphila.
AB  - BACKGROUND: The biocatalytic oxidation of UDP-glucose in the presence of NAD+ is
      catalyzed by UDP-glucose dehydrogenases. OBJECTIVES: The main objective of this
      study was the characterization of a UDP-glucose dehydrogenase (AmUGD) from
      Akkermansia muciniphila, a bacterium originally isolated from human faeces in an
      anaerobic medium containing gastric mucin as the sole carbon source. METHODS: The
      biochemical analysis of AmUGD was performed using a plate reader-based assay
      measuring the reaction by-product NADH. Furthermore, HPLC- and MALDI-ToF-MS-
      based methods were used for the enzyme characterization. RESULTS: The recombinant
      form of the protein was expressed in E. coli and the purified enzyme exhibited
      optimum levels of activity at 37 degrees C and pH 9.0. While the enzyme is active
      in the absence of metal ions, the presence of Zn2+ ions results in markedly
      enhanced levels of catalysis. CONCLUSION: This study describes the first
      characterization of a nucleotide-processing enzyme from A. muciniphila. The ease
      of expression and purification of this enzyme make it ideal for biotechnological
      applications such as the enzymatic synthesis of nucleotide sugars, which may in
      turn be used for the synthesis of complex carbohydrates or glycoconjugates.

PMID- 28741461
TI  - The Enzymatic Degradation of Heparan Sulfate.
AB  - Glycosaminoglycans (GAGs) such as heparan sulfate (HS) interact with a number of
      factors in the extracellular matrix (ECM) and as a consequence play a key role in
      the metabolic processes occurring within the cell. The dynamic synthesis and
      degradation of HS (and all GAGs) are necessary for ensuring that optimal chains
      are present for these functions. The degradation of HS begins at the cell surface
      and finishes in the lysosome, after which components can be recycled.
      Deficiencies or mutations in the lysosomal enzymes that process GAGs result in
      rare Mucopolysaccharidoses disorders (MPSs). There are few treatments available
      for these genetically inherited diseases and those that are available often do
      not treat the neurological symptoms of the disease. In this review, we discuss
      the enzymes involved in the degradation of HS and their related diseases, with
      emphasis on those located in the lysosome.

PMID- 28741462
TI  - Development of a Solid Phase Array Assay for the Screening of Galactose Oxidase
      Activity and for Fast Identification of Inhibitors.
AB  - BACKGROUND: Galactose oxidase (GOase) catalyses the highly selective oxidation of
      terminal galactosides on a wide range of natural glycoconjugates and has found
      wide applications in biotechnology - particularly in biocatalysis. GOase is
      copper dependent and uses oxygen to oxidise the C6-primary alcohol of galactose
      and produces hydrogen peroxide. The enzyme activity can be conveniently assessed
      by a colorimetric assay. OBJECTIVES: The objective of the present study was to
      develop an assay system, which is independent of the hydrogen peroxide formation
      to identify possible fluorinated GOase inhibitors. In case that the inhibitor
      bears a primary or secondary alcohol, it could also be oxidised by the enzyme. In
      such case, the colorimetric assay is not able to distinguish between substrate
      and inhibitor, since oxidation of both molecules would result in the formation of
      hydrogen peroxide. METHODS: D-galactose (D-Gal) was immobilised onto a gold
      surface functionalised by selfassembled monolayers (SAMs,). A GOase solution was
      then added to the surface in a droplet for a certain period of time and
      thereafter washed away. The activity of GOase on the immobilised D-Gal can then
      be quantified by MALDI-ToF MS. RESULTS: For inhibition studies, GOase was
      incubated together with 62.5 mM of deoxy-fluorinated monosaccharides on the D-Gal
      displaying platform. Five deoxy-fluorinated D-Gal showed a >50% inhibition of its
      activity. The array system has been moreover utilised to determine the apparent
      IC50 value of 3-F-Gal 15 as a proof of principle. CONCLUSION: The developed array
      platform allows the fast identification of GOase substrates and inhibitors from a
      library of deoxy-fluorinated sugars using MALDI-ToF MS as a label-free readout
      method. In addition, the enzymatic reaction enables for the in situ activation of
      sugar-coated surfaces to bioorthogonal aldehydes, which can be utilised for
      subsequent chemical modifications.

PMID- 28741463
TI  - Effect of Organic Solvents on Porcine Pancreatic Lipase Thermal Aggregation.
AB  - BACKGROUND: Proteins tend to form inactive aggregates under harsh conditions used
      in industrial processes. Lipases are enzymes that hydrolyse triglycerides to
      glycerol and free fatty acids, but are able to catalyse various other
      transformations in the presence of organic solvents. OBJECTIVES: The main
      objective of this study was to investigate lipases behavior at high temperature
      and in presence of organic solvents. METHODS: Heat-induced aggregation of porcine
      pancreatic lipase (PPL) was followed by UV-visible spectroscopy at 400 nm
      wavelength for 600 seconds, at the isoelectric point (pH 5, phosphate solution)
      and 50 degrees C, and in presence or absence of various percentages of dimethyl
      sulfoxide (DMSO), propanol, isopropanol, acetone and trifluoroethanol (TFE).
      Possible positioning of each organic solvent molecule relative to PPL was
      investigated using docking method. RESULTS: Native enzyme aggregated under
      aforementioned conditions and amorphous aggregates formed which were visible to
      the naked eye. From the tested solvents, DMSO reduced protein aggregation in a
      concentration-dependent manner. On the other hand, protein aggregation
      intensified by adding any of propanol, isopropanol, acetone or TFE. This effect
      was more pronounced in TFE and propanol compared to isopropanol and acetone.
      CONCLUSION: Solvents with lower polarity led to aggregation, while solvent with
      higher polarity inhibited PPL aggregation, and DMSO could be effectively used to
      counteract lipase aggregation.

PMID- 28741464
TI  - Expression of Mastoparan B, a Venom Peptide, Via Escherichia coli C43 (DE3)
      Coupled with an Artificial Oil Body-Cyanogen Bromide Technology Platform.
AB  - BACKGROUND: Mastoparan B (MPB) is a venom peptide isolated from Vespa basalis
      (black-bellied hornet), one of the dangerous vespine wasps found in Taiwan. MPB
      is a tetradecapeptide (LKLKSIVSWAKKVL), amphiphilic venom peptide, with a
      molecular mass of 1.6 kDa. MPB belongs to an evolutionarily conserved component
      of the innate immune response against microbes. In this study, we attempted to
      modify a reliable oleosin-based fusion expression strategy coupled with the
      artificial oil body (AOB)-cyanogen bromide (CNBr) platform to produce bioactive
      MPB. OBJECTIVES: The aim of this study was to develop an artificial oil body
      (AOB)-cyanogen bromide (CNBr) platform to produce the bioactive form of
      mastoparan B (MPB), which in a manner identical to that of its native
      counterpart. METHODS: The plasmid pET30-His6-rOle(127M->L)-MPB was constructed,
      and then four different E. coli strains- BL21(DE3), BL21(DE3)pLysS, C41(DE3), and
      C43(DE3) were tested to identify the most suitable host for the pET30-His6
      rOle(127M->L)-MPB fusion protein expression. We optimized the expression
      conditions by testing different growth temperatures, isopropyl-beta-D
      thiogalactoside (IPTG) concentrations, and post-induction collection times.
      Afterwards, the His6-rOle(127M->L)-MPB protein was purified by one-step nickel
      chelated affinity chromatography (Ni2+-NTA) under denaturing conditions. The
      purified His6-rOle(127M->L)-MPB was selectively cleaved by thrombin protease to
      remove the His6-tag and the leader peptide from the N-terminus. Subsequently,
      rOle(127M->L)-MPB protein was constituted into AOB and incubated with CNBr for a
      cleavage reaction, which resulted in the release of the MPB from rOle(127M->L)
      MPB protein via AOB. The purified MPB was identified by MALDI-MS and HPLC
      analysis, and its bioactivity was examined by antimicrobial testing. RESULTS:
      After a 2-h induction period, the E. coli C43(DE3) was found to be superior to
      BL21(DE3) and the other protease-deficient strains as an expression host. And,
      the optimal His6-rOle(127M->L)-MPB expression at 37 degrees C for 2 h after
      induction with 5 uM IPTG. The purified MPB showed that a single major peak was
      detected by HPLC/UV detection with a retention time of 22.5 minutes, which was
      approximately 90% pure. The putative MPB, and over two-third of the peptide
      sequence was verified by the MALDI-MS analysis. Finally, the purified MPB was
      examined by a broth dilution-antimicrobial susceptibility test. These results
      indicated that the purified MPB was bioactive and very effective in anti
      bacterial (E. coli J96) activity. Here, we successfully used the oleosin-based
      fusion expression strategy coupled with the artificial oil body (AOB)-cyanogen
      bromide (CNBr) platform to produce bioactive MPB peptide which, in a manner
      identical to that of its native counterpart. CONCLUSION: In this study, the
      recombinant oleosin based fusion strategy coupled with AOB-CNBr purification
      platform open a new avenue for the production of active MPB and facilitate the
      studies and applications of the peptide in the future for medicinal applications
      such as hypotension and antibacterial effect.

PMID- 28741465
TI  - Engineering of Chimeric Protein Based on E Protein Domain III of Tick- Borne
      Encephalitis Virus and OmpF Porin of Yersinia pseudotuberculosis.
AB  - BACKGROUND: Tick-borne encephalitis poses a serious public health threat in the
      endemic regions. The disease treatment is restricted to symptomatic therapy, so
      great expectations are in the development of the prophylactic and therapeutic
      vaccines. The domain III of E protein of the tickborne encephalitis virus is the
      main antigenic domain which includes virus-specific epitopes recognized by
      neutralizing antibodies. OBJECTIVES: The main objective of this study was to
      design, express, isolate and characterize the chimeric protein based on the
      fusion of domain III of E protein of the tick-borne encephalitis virus and
      bacterial porin OmpF from Yersinia pseudotuberculosis. METHODS: The chimeric gene
      was obtained by the PCR based fusion method from two fragments containing
      overlapping linker sequences. Resulting plasmids were transformed into BL21(DE3)
      pLysS electrocompetent cells for subsequent heterologous protein expression. All
      recombinant proteins were purified using immobilized metal affinity
      chromatography under denaturing conditions. The identity of the chimeric protein
      was confirmed by MALDI-TOF mass spectrometry and immunoblot analysis. The content
      of antibodies against the EIII protein was estimated in mice blood serum by
      ELISA. RESULTS: The bacterial partner protein was used for decreasing toxicity
      and increasing immunogenicity of antigen. The chimeric protein was successfully
      expressed by the Escherichia coli cells. The purified protein was recognized with
      immunoblots by anti-E protein of tick-borne encephalitis virus monoclonal
      antibodies. Furthermore, the protein was able to elicit antibody response against
      domain III of E protein in immunized mice. CONCLUSION: The newly obtained
      chimeric antigen could be valuable for the development of the preventing tick
      borne encephalitis subunit vaccines.

PMID- 28741466
TI  - Binding of CXCR4 Transmembrane Peptides to the Bacterial Chaperonin GroEL.
AB  - BACKGROUND: The Escherichia coli chaperonin GroEL represents the paradigmatic
      molecular machine of protein folding. Most of our knowledge on GroEL function is
      derived from studies with denatured water-soluble proteins or short peptide
      mimetics. In our earlier studies, we observed that newly translated membrane
      protein CXCR4 gained significant folding enhancement upon interacting with GroEL
      in the presence of ATP and GroES. This highlights the mechanistic flexibility and
      substrate diversity of the chaperonin. OBJECTIVES: This work extends our previous
      observation to the study of binding of GroEL with CXCR4 transmembrane peptides.
      METHODS: The model peptide corresponding to the first transmembrane alpha-helix
      in the native tertiary structure of CXCR4 was commercially synthesized. A
      fluorescent tag was attached to the Nterminus of the peptide for ease of
      fluorescence characterization. Binding of CXCR4 peptide to GroEL was investigated
      by fluorescence anisotropy as well as isothermal titration calorimetry (ITC).
      Through model fitting to the anisotropy and ITC data, important thermodynamic
      parameters were obtained for the binding. In identifying the binding site of
      GroEL apical domains for the CXCR4 peptide, competitive binding of the peptide
      and a model "strongly binding peptide" (SBP) was performed by ITC. Furthermore,
      the kinetics of the CXCR4 peptide binding to GroEL was also studied by
      anisotropy. RESULTS: Through anisotropic measurement of binding of CXCR4 peptide
      to GroEL, a dissociation constant and binding stoichiometry of 0.10uM and 7.00
      was obtained. Thermodynamic parameters of the binding were also determined by
      ITC. By fitting the ITC data to one set of sites model, the values of the
      thermodynamic parameters were acquired directly as follows: DeltaH=
      627.10kcal/mol; DeltaS=-186.23cal/mol; KD=0.23uM; N=5.96. The binding site of the
      CXCR4 peptide in GroEL was also probed through competitive binding with the model
      peptide SBP, pointing to the groove between paired alpha helices H and I in the
      apical domain. In addition, the binding kinetics suggests a slow dissociation of
      the peptide-GroEL complex. CONCLUSION: The CXCR4 model peptide has been shown to
      bind to GroEL with high affinity. The binding stoichiometry was estimated to be 6
      or 7 depending on the analysis method. Furthermore, the two thermodynamic
      parameters DeltaH and DeltaS that define the binding affinity have also been
      measured by ITC. The binding site of the CXCR4 peptide in the GroEL apical domain
      was investigated through competitive binding studies with the model peptide SBP.
      Meanwhile, the kinetic studies indicate a slow dissociation of the peptide-GroEL
      complex. These results obtained by the reduced approach of employing CXCR4
      transmembrane peptides would be beneficial to understanding the GroEL-CXCR4
      interaction in the assisted folding.

PMID- 28741467
TI  - Status Quo in Antibody-Drug Conjugates - Can Glyco- Enzymes Solve the Current
      Challenges?
AB  - Over the last years, a novel class of anti-cancer drugs named antibody-drug
      conjugates (ADCs) has been developed. Due to their limited off-target toxicity
      but highly potent cytotoxicity at tumor sites, ADCs have proven to be a good
      alternative to ordinary cancer treatment, such as chemotherapy or combination
      therapy. Numerous enhancements in antibody-drug engineering led to highly potent
      tumor targeting drugs with a wide therapeutic window. Two ADCs (Brentuximab
      vedotin and Trastuzumab emtansine) are already on the market and many others are
      in clinical trials. However, unstable linkers, low drug potency and unwanted
      bystander-effects are only some of the drawbacks of ADCs. Enzymes used in
      combination with prodrugs happen to be a promising alternative. The glyco-enzyme
      horseradish peroxidase (HRP) has proven to activate the hormone indole-3-acetic
      acid (IAA) to a highly potent cytotoxic drug. This combination of IAA and HRP has
      been investigated for the use in strategies such as gene-directed enzyme prodrug
      therapy (GDEPT) and antibody-directed enzyme prodrug therapy (ADEPT). This
      article reviews the current state of research in ADC engineering and describes
      the potential major enhancements through use of glycoenzymes in combination with
      a prodrug.

PMID- 28741468
TI  - Development of Standard Reference Material (SRM) 2973 Vitamin D Metabolites in
      Frozen Human Serum (High Level).
AB  - The National Institute of Standards and Technology (NIST), in collaboration with
      the National Institutes of Health Office of Dietary Supplements and the Vitamin D
      Standardization Program, has recently issued a new serum-matrix Standard
      Reference Material (SRM): 2973 Vitamin D Metabolites in Frozen Human Serum (High
      Level). SRM 2973 was designed to provide a serum material with a total 25
      hydroxyvitamin D [25(OH)D] concentration near 100 nmol/L to complement the
      existing serum-based SRMs with values assigned for total 25(OH)D between 20 and
      80 nmol/L. Values were assigned for 25-hydroxyvitamin D2 [25(OH)D2], 25
      hydroxyvitamin D3 [25(OH)D3], 3-epi-25(OH)D3 , and total 25(OH)D [the sum of
      25(OH)D2 + 25(OH)D3] using the NIST isotope dilution LC with tandem MS (MS/MS)
      reference measurement procedure (RMP) and related methods. SRM 2973 has a
      certified value of 98.4 +/- 2.1 nmol/L for 25(OH)D3 and reference values of 1.59
      +/- 0.05 nmol/L for 25(OH)D2 and 5.23 +/- 0.20 nmol/L for 3-epi-25(OH)D3 . In
      addition, a candidate RMP for 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] based on
      LC-MS/MS was used to assign values to SRM 2973 and the existing SRM 972a Vitamin
      D Metabolites in Frozen Human Serum. Reference values for 24R,25(OH)2D3 were
      assigned to SRM 2973 (7.51 +/- 0.26 nmol/L) and the four levels of SRM 972a:
      Level 1 (6.38 +/- 0.23 nmol/L), Level 2 (3.39 +/- 0.12 nmol/L), Level 3 (3.88 +/-
      0.013 nmol/L), and Level 4 (6.32 +/- 0.22 nmol/L). The development of SRM 2973
      [with a higher concentration of 25(OH)D3] and the addition of values for
      24R,25(OH)2D3 assigned to both SRM 972a and SRM 2973 provide laboratories
      involved in vitamin D measurements with improved QA tools.

PMID- 28741469
TI  - Interlaboratory Comparison for the Determination of 24,25-Dihydroxyvitamin D3 in
      Human Serum Using Liquid Chromatography with Tandem Mass Spectrometry.
AB  - Six laboratories associated with the Vitamin D Standardization Program (VDSP)
      participated in an interlaboratory comparison of LC with tandem MS (MS/MS)
      methods for the determination of 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] in
      human serum. The laboratories analyzed two different serum-based Standard
      Reference Materials (SRMs) intended for use in the determination of 25
      hydroxyvitamin D and 30 samples from the Vitamin D External Quality Assessment
      Scheme (DEQAS). All laboratory methods for 24,25(OH)2D3 were based on isotope
      dilution LC-MS/MS; three of the methods used derivatization of the vitamin D
      metabolites before LC-MS/MS. Laboratory results were compared to the National
      Institute of Standards and Technology (NIST) results, which were obtained using
      their newly developed candidate reference measurement procedure for 24,25(OH)2D3.
      Laboratory results for the SRM samples varied in comparability to the NIST
      results, with one laboratory in excellent agreement (-1.6% mean bias), three
      laboratories at 10-15% mean bias, and the remaining laboratory at 36% mean bias.
      For the 30 DEQAS samples, the mean bias for the five laboratories ranged from 6
      to 15%; however, the SD of the bias ranged from 8 to 29%. As a result of this
      intercomparison study, one laboratory discovered and corrected a method
      calculation error and another laboratory modified and improved their LC-MS/MS
      method.

PMID- 28741470
TI  - Ecological feedback in quorum-sensing microbial populations can induce
      heterogeneous production of autoinducers.
AB  - Autoinducers are small signaling molecules that mediate intercellular
      communication in microbial populations and trigger coordinated gene expression
      via 'quorum sensing'. Elucidating the mechanisms that control autoinducer
      production is, thus, pertinent to understanding collective microbial behavior,
      such as virulence and bioluminescence. Recent experiments have shown a
      heterogeneous promoter activity of autoinducer synthase genes, suggesting that
      some of the isogenic cells in a population might produce autoinducers, whereas
      others might not. However, the mechanism underlying this phenotypic heterogeneity
      in quorum-sensing microbial populations has remained elusive. In our theoretical
      model, cells synthesize and secrete autoinducers into the environment, up
      regulate their production in this self-shaped environment, and non-producers
      replicate faster than producers. We show that the coupling between ecological and
      population dynamics through quorum sensing can induce phenotypic heterogeneity in
      microbial populations, suggesting an alternative mechanism to stochastic gene
      expression in bistable gene regulatory circuits.

PMID- 28741472
TI  - Chromatin Structure Profiling Identifies Crucial Regulators of Tumor Maintenance.
AB  - Cancer is primarily caused by mutations in genes encoding transcriptional
      regulators and signaling molecules. These mutations cooperate to deregulate the
      tight control over gene expression that is otherwise seen in normal cells. One
      consequence of this process is deregulated transcription factor (TF) activity.
      This forum article highlights novel strategies that use genome-wide chromatin
      structure profiling to identify the deregulated factors on which cancer cells
      depend, with the ultimate aim of targeting them.

PMID- 28741471
TI  - Altered paracrine signaling from the injured knee joint impairs postnatal long
      bone growth.
AB  - Regulation of organ growth is a poorly understood process. In the long bones, the
      growth plates (GPs) drive elongation by generating a scaffold progressively
      replaced by bone. Although studies have focused on intrinsic GP regulation,
      classic and recent experiments suggest that local signals also modulate GP
      function. We devised a genetic mouse model to study extrinsic long bone growth
      modulation, in which injury is specifically induced in the left hindlimb, such
      that the right hindlimb serves as an internal control. Remarkably, when only
      mesenchyme cells surrounding postnatal GPs were killed, left bone growth was
      nevertheless reduced. GP signaling was impaired by altered paracrine signals from
      the knee joint, including activation of the injury response and, in neonates,
      dampened IGF1 production. Importantly, only the combined prevention of both
      responses rescued neonatal growth. Thus, we identified signals from the knee
      joint that modulate bone growth and could underlie establishment of body
      proportions.

PMID- 28741473
TI  - Why Does Infection With Some Helminths Cause Cancer?
AB  - Infections with Opisthorchis viverrini, Clonorchis sinensis, and Schistosoma
      haematobium are classified as group 1 biological carcinogens: definitive causes
      of cancer. These worms are metazoan eukaryotes, unlike the other group 1
      carcinogens including human papilloma virus, hepatitis C virus, and Helicobacter
      pylori. By contrast, infections with phylogenetic relatives of these helminths,
      also trematodes of the phylum Platyhelminthes and major human pathogens, are not
      carcinogenic. These inconsistencies prompt several questions, including how might
      these infections cause cancer, and why is infection with only a few helminth
      species carcinogenic? We present an interpretation of mechanisms contributing to
      the carcinogenicity of these helminth infections, including roles for metabolites
      of catechol estrogen and oxysterols of parasite origin as initiators of
      carcinogenesis.

PMID- 28741474
TI  - Modeling Normal and Disordered Human Hematopoiesis.
AB  - Similarities between the organization of the blood-forming system in humans and
      mice, and the ease of genetically manipulating and assessing primitive mouse
      hematopoietic cells, has made this species a model of choice. However, important
      differences exist in the role of specific gene products in regulating analogous
      steps in the generation of particular blood cell types in humans and mice, as
      well as in the perturbations that the same mutations elicit in hematopoietic
      cells from the two species. At the same time, the methods to generate and
      propagate normal and genetically altered human hematopoietic cells are
      increasingly permissive, and progress towards humanized mice is advancing
      rapidly. We review the incomplete fidelity of the mouse system in modeling human
      hematopoiesis, and highlight advances that portend a shift towards studies
      focused directly on human cells.

PMID- 28741476
TI  - Squamous Transition of Lung Adenocarcinoma and Drug Resistance.
AB  - Studies in mouse models support an essential role of lung adenocarcinoma (ADC) to
      squamous cell carcinoma (SCC) transition (AST) in the development of drug
      resistance. Recent observations in the clinic further suggest that this type of
      histological transition may be responsible for resistance to tyrosine kinase
      inhibitor (TKI) therapy and chemotherapy in relapsed EGFR-mutant lung ADC
      patients. Here we summarize the current understanding of AST and drug resistance.

PMID- 28741478
TI  - Targeting the Microenvironment in Advanced Colorectal Cancer.
AB  - Colorectal cancer (CRC) diagnosis often occurs at late stages when tumor cells
      have already disseminated. Current therapies are poorly effective for metastatic
      disease, the main cause of death in CRC. Despite mounting evidence implicating
      the tumor microenvironment in CRC progression and metastasis, clinical practice
      remains predominantly focused on targeting the epithelial compartment. Because
      CRCs remain largely refractory to current therapies, we must devise alternative
      strategies. Transforming growth factor (TGF)-beta has emerged as a key architect
      of the microenvironment in poor-prognosis cancers. Disseminated tumor cells show
      a strong dependency on a TGF-beta-activated stroma during the establishment and
      subsequent expansion of metastasis. We review and discuss the development of
      integrated approaches focused on targeting the ecosystem of poor-prognosis CRCs.

PMID- 28741479
TI  - Colorectal Cancer Subtypes: Developmental Origin and Microenvironmental
      Regulation.
AB  - Cancer is a heterogeneous disease and many cancer types do not represent a single
      entity, but are composed of biologically and clinically diverse subtypes. The
      subtype affiliation can influence prognosis and response to therapy. Recently, a
      multicenter colorectal cancer (CRC) subtyping consortium introduced a consensus
      molecular classification system for CRC. This will be of great benefit for future
      basic and clinical research since it enables uniform categorization of CRC
      specimens across different institutes and studies. The biological conformity
      observed within each consensus molecular subtype (CMS) holds promise for the
      design of subtype-specific treatment regimens. Herein, we review the CMSs of CRC
      with a focus on how multiple parameters, such as the origin, developmental route,
      and microenvironmental regulation shape distinct subtypes.

PMID- 28741480
TI  - Cadherins Glycans in Cancer: Sweet Players in a Bitter Process.
AB  - Cadherins are key components in tissue morphogenesis and architecture,
      contributing to the establishment of cohesive cell adhesion. Reduced cellular
      adhesiveness as a result of cadherin dysfunction is a defining feature of cancer.
      During tumor development and progression, major changes in the glycan repertoire
      of cancer cells take place, affecting the stability, trafficking, and cell
      adhesion properties of cadherins. Importantly, the different glycoforms of
      cadherins are promising biomarkers, with potential clinical application to
      improve the management of patients, and constitute targets for the development of
      new therapies. This review discusses the most recent insights on the impact of
      glycan structure on the regulation of cadherin function in cancer, and provides a
      perspective on how cadherin glycans constitute tumor biomarkers and potential
      therapeutic targets.

PMID- 28741481
TI  - The New Frontiers in Cancer.

PMID- 28741482
TI  - Jose Baselga: A Vision and Roadmap for Cancer Research.

PMID- 28741483
TI  - Jennifer Doudna: Tailoring the Genome.

PMID- 28741484
TI  - Suzanne Cory: Life-and-Death Switches: the Rise of BH3 Mimetics.

PMID- 28741485
TI  - Barbara Dunn: Preventing Cancer.

PMID- 28741486
TI  - Rethinking Lymphatic Vessels and Antitumor Immunity.
AB  - Lymphatic vessels facilitate fluid homeostasis, immune cell trafficking, and
      lipid transport, and contribute to solid tumor progression as routes of
      metastasis. Given new evidence that lymphatic vessels both correlate with
      intratumoral lymphocytes and directly suppress immune function, I reevaluate the
      passive lymphatic vessel paradigm and discuss its relevance to antitumor
      immunity.

PMID- 28741487
TI  - Difference Makers: Chromosomal Instability versus Aneuploidy in Cancer.
AB  - Human cancers harbor great numbers of genomic alterations. One of the most common
      alterations is aneuploidy, an imbalance at the chromosome level. Some aneuploid
      cancer cell populations show varying chromosome copy number alterations over
      time, a phenotype known as 'chromosomal instability' (CIN). Chromosome
      segregation errors in mitosis are the most common cause for CIN in vitro, and
      these are also thought to underlie the aneuploidies seen in clinical cancer
      samples. However, CIN and aneuploidy are different traits and they are likely to
      have distinct impacts on tumor evolution and clinical tumor behavior. In this
      opinion article, we discuss these differences and describe scenarios in which
      distinguishing them can be clinically relevant.

PMID- 28741488
TI  - Extraordinary Cancer Epigenomics: Thinking Outside the Classical Coding and
      Promoter Box.
AB  - The advent of functional genomics powered by high-throughput sequencing has given
      us a new appreciation of the genomic sequences that lie outside the canonical
      promoter-coding sequence box. These regions harbor distant regulatory elements,
      enhancers, super-enhancers, insulators, alternative promoters, and sequences that
      transcribe as noncoding RNAs (ncRNAs) such as miRNAs and long ncRNAs. These
      functional genomics studies have also enabled a clearer understanding of the role
      of the 3D structure of the genome in epigenetic regulation. Here we review the
      impact that epigenetic changes, and specifically DNA methylation, have on these
      extraordinary sequences in driving cancer progression.

PMID- 28741489
TI  - Epigenomic Consequences of Coding and Noncoding Driver Mutations.
AB  - Chromatin alterations are integral to the pathogenic process of cancer, as
      demonstrated by recent discoveries of frequent mutations in chromatin-modifier
      genes and aberrant DNA methylation states in different cancer types. Progress is
      being made on elucidating how chromatin alterations, and how proteins catalyzing
      these alterations, mechanistically contribute to tissue-specific tumorigenesis.
      In parallel, technologies enabling the genome-wide profiling of histone
      modifications have revealed the existence of noncoding driver genetic alterations
      in cancer. In this review, we survey the current knowledge of coding and
      noncoding cancer drivers, and discuss their impact on the chromatin landscape.
      Translational implications of these findings for novel cancer therapies are also
      presented.

PMID- 28741490
TI  - In Vivo RNAi Screening for Pancreatic Cancer Drivers: PILOTing the WDR5-MYC Axis.
AB  - Pancreatic ductal adenocarcinoma (PDAC) represents a major global health problem
      that causes over 200000 deaths each year worldwide. The disease is highly
      resistant to cytotoxic and targeted therapies and the average survival is less
      than 12 months. This situation prompted Alessandro Carugo and Giulio Draetta to
      develop a novel genetic mouse system, termed Patient-Based In Vivo Lethality to
      Optimize Treatment (PILOT), to perform functional RNAi-based in vivo screens to
      uncover and target PDAC drivers. In a forward genetic screen focused on
      epigenetic modifiers, a WDR5-Myc axis that regulates the DNA replication
      checkpoint was identified and exploited in vivo for therapeutic intervention.

PMID- 28741491
TI  - Watson for Genomics: Moving Personalized Medicine Forward.
AB  - The confluence of genomic technologies and cognitive computing has brought us to
      the doorstep of widespread usage of personalized medicine. Cognitive systems,
      such as Watson for Genomics (WG), integrate massive amounts of new omic data with
      the current body of knowledge to assist physicians in analyzing and acting on
      patient's genomic profiles.

PMID- 28741492
TI  - Small Intestinal Cancer: Why the Rarity?

PMID- 28741493
TI  - Derisking Drug-Induced Carcinogenicity for Novel Therapeutics.
AB  - Assessing the carcinogenic potential of innovative drugs spanning diverse
      therapeutic modalities and target biology represents a major challenge during
      drug development. Novel modalities, such as cell and gene therapies that involve
      intrinsic genetic modification of the host genome, require distinct approaches
      for identification of cancer hazard. We emphasize the need for customized weight
      of-evidence cancer risk assessments based on mode of action that balance multiple
      options for preclinical identification of cancer hazard with appropriate labeling
      of clinical products and risk management plans. We review how advances in
      molecular carcinogenesis can enhance mechanistic interpretation and preclinical
      indicators of neoplasia, and recommend that drug targets be systematically
      assessed for potential association with tumorigenic phenotypes via genetic models
      and cancer genome resources.

PMID- 28741494
TI  - Evolutionary Ecology of Organs: A Missing Link in Cancer Development?
AB  - There is striking variation in the incidence of cancer in human organs. Malignant
      tumors are common in the colon and breast but rare in the heart and small bowel.
      The uterus frequently develops benign fibroid tumors but uterine cancers are
      relatively rare. The organ-specific difference in cancer prevalence has been
      explained primarily by the relative roles of intrinsic and extrinsic risk
      factors. In this opinion article, we propose also considering organs as distinct
      but connected ecosystems whose different vulnerabilities to malignant
      transformation may be partially explained by how essential each organ is for
      survival through the age of reproduction. We present and discuss some of the
      basic concepts and assumptions of this perspective on evolutionary medicine.

PMID- 28741495
TI  - Adaptive Stress Responses During Tumor Metastasis and Dormancy.
AB  - To survive inhospitable environments, tumor cells are forced to remodel their
      signaling pathways by altering transcription, translation, and post-translational
      modifications. This adaptation is regulated in a spatial and temporal manner and
      gives rise to individual tumor cells with distinct gene expression and metabolic
      signatures. Such phenotypic heterogeneity is the result of tumor cell plasticity,
      which-together with the genetic background of the tumor-determines whether cells
      resist environmental stress, enter dormancy, or metastasize. This review
      summarizes our understanding of how tumor cells exploit the cellular stress
      response to balance proliferation, differentiation, and survival signals, as well
      as to remodel local and distant environments. We focus in particular on tumor
      metastasis, which is the greatest impediment to clinical management of cancers
      today.

PMID- 28741496
TI  - Targeting BCL-2-like Proteins to Kill Cancer Cells.
AB  - Mutations that impair apoptosis contribute to cancer development and reduce the
      effectiveness of conventional anti-cancer therapies. These insights and
      understanding of how the B cell lymphoma (BCL)-2 protein family governs apoptosis
      have galvanized the search for a new class of cancer drugs that target its pro
      survival members by mimicking their natural antagonists, the BCL-2 homology (BH)3
      only proteins. Successful initial clinical trials of the BH3 mimetic
      venetoclax/ABT-199, specific for BCL-2, have led to its recent licensing for
      refractory chronic lymphocytic leukemia and to multiple ongoing trials for other
      malignancies. Moreover, preclinical studies herald the potential of emerging BH3
      mimetics targeting other BCL-2 pro-survival members, particularly myeloid cell
      leukemia (MCL)-1, for multiple cancer types. Thus, BH3 mimetics seem destined to
      become powerful new weapons in the arsenal against cancer. This review sketches
      the discovery of the BCL-2 family and its impact on cancer development and
      therapy; describes how interactions of family members trigger apoptosis; outlines
      the development of BH3 mimetic drugs; and discusses their potential to advance
      cancer therapy.

PMID- 28741497
TI  - MYC: A Stratification Marker for Pancreatic Cancer Therapy.
AB  - One approach to improve cancer treatment is to stratify patients and to develop
      subgroup-specific therapies. We will discuss the potential of MYC as a
      stratification marker in pancreatic ductal adenocarcinoma. Furthermore, we will
      point to possibilities for how to annotate the MYC status and how to target MYC
      associated vulnerabilities.

PMID- 28741498
TI  - Intercellular Conduits in Tumors: The New Social Network.
AB  - The role of intercellular communication is increasingly recognized as being
      critical to tumoral invasion, metastasis, and development of resistance to
      therapy. The recent discovery of cellular protrusions - tumor microtubes -
      connecting cancer cells in gliomas, and tunneling nanotubes in several other
      forms of cancer, sheds light on a novel mechanism for molecular networking.
      Interrupting and disrupting vital lines of intercellular crosstalk via these
      membranous cellular tubes has strong potential as a novel form of cancer-directed
      therapy.

PMID- 28741499
TI  - Targeting Androgen/Estrogen Receptors Crosstalk in Cancer.
AB  - The actions of estrogens are mediated by estrogen receptors, ERalpha and ERbeta.
      Recent genomic landscaping of ERalpha- and ERbeta-binding sites has revealed
      important distinctions regarding their transcriptional activity. ERbeta and its
      isoforms have been correlated with endocrine treatment responsiveness in breast
      tumors, while post-translational modifications, receptor dimerization patterns,
      and subcellular localization are increasingly recognized as crucial modulators in
      prostate carcinogenesis. Androgen receptor (AR) is essential for the development
      and progression of prostate cancer as well as of certain breast cancer types. The
      balance between the activity of these two hormone receptors and their molecular
      interactions in different clinical settings is influenced by several
      coregulators. This comprises a dynamic regulatory network enhancing or limiting
      the activity of AR-directed treatments in breast and prostate tumorigenesis. In
      this review, we discuss the molecular background regarding the therapeutic
      targeting of androgen/estrogen receptor crosstalk in breast and prostate cancer.

PMID- 28741500
TI  - Immunity Gone Astray - NETs in Cancer.
AB  - Neutrophil extracellular traps (NETs) have emerged as significant contributors to
      cancer-associated pathologies such as metastasis, thrombosis, and organ
      dysfunction in preclinical models. We review recent discoveries of the
      involvement of NETs in human cancers and suggest tumor-induced NET formation as
      an interesting potential therapeutic target in oncology.

PMID- 28741501
TI  - Retinoblastoma Binding Protein 6, Another p53 Monitor.
AB  - The retinoblastoma binding protein 6 (RBBP6), a p53 negative regulator, is
      essential for embryonic development. Its loss-of-function phenotype is similar to
      mouse double minute homolog (MDM2), the prototypical negative regulator of p53.
      This article draws attention to the molecular and biological functions of RBBP6
      and to its association with carcinogenesis.

PMID- 28741502
TI  - Immune Priming of the Tumor Microenvironment by Radiation.
AB  - Ionizing irradiation can induce a multitude of alterations within the tumor
      microenvironment. Unlike targeted therapies, radiation delivered to the tumor bed
      can prompt phenotypic changes in both normal stromal and cancer cells, leading to
      molecular and physiological alterations within the tumor microenvironment. These
      environmental modulations directly influence the degree of immunogenicity of the
      tumor microenvironment and may ultimately affect tumor responsiveness to cancer
      immunotherapies. Here we review the preclinical evidence for tumor
      microenvironment-mediated immune suppression and how radiation can modulate
      immune properties within a tumor. We then discuss the therapeutic opportunities
      for combining radiation with molecular agents to enhance tumor immunogenicity and
      how this represents a potential exciting strategy to complement immunotherapies
      including immune checkpoint blockers in cancer treatment.

PMID- 28741503
TI  - The 'Pushmi-Pullyu' of DNA REPAIR: Clinical Synthetic Lethality.
AB  - Maintenance of genomic integrity is critical for adaptive survival in the face of
      endogenous and exogenous environmental stress. The loss of stability and fidelity
      in the genome caused by cancer and cancer treatment provides therapeutic
      opportunities to leverage the critical balance between DNA injury and repair.
      Blocking repair and pushing damaged DNA through the cell cycle using therapeutic
      inhibitors exemplify the 'pushmi-pullyu' effect of disrupted DNA repair. DNA
      repair inhibitors (DNARi) can be separated into five biofunctional categories:
      sensors, mediators, transducers, effectors, and collaborators that recognize DNA
      damage, propagate injury DNA messages, regulate cell cycle checkpoints, and alter
      the microenvironment. The result is cancer therapeutics that takes advantage of
      clinical synthetic lethality, resulting in selective tumor cell kill. Here, we
      review recent considerations related to DNA repair and new DNARi agents and
      organize those findings to address future directions and clinical opportunities.

PMID- 28741504
TI  - Eradicating Quiescent Tumor Cells by Targeting Mitochondrial Bioenergetics.
AB  - The presence of quiescent cell populations in solid tumors represents a major
      challenge for disease eradication. Such cells are generally present in poorly
      vascularized tumor areas, show limited sensitivity to traditional
      chemotherapeutical drugs, and tend to resume proliferation, resulting in tumor
      reseeding and growth. There is growing recognition of the importance of
      developing therapies that target these quiescent cell populations to achieve long
      lasting remission. Recent studies have shown that the combination of hypoxia and
      reduced nutrient availability in poorly vascularized areas results in limited
      tumor metabolic plasticity coupled with an increased sensitivity to perturbations
      in mitochondrial flux. Targeting of mitochondrial bioenergetics in these
      quiescent cell tumor populations may enable tumor eradication and improve the
      prognosis of patients with cancer.

PMID- 28741505
TI  - Emerging Roles for Eosinophils in the Tumor Microenvironment.
AB  - Eosinophils are evolutionary conserved cells largely studied in the context of
      allergy. Although eosinophils were first described in tumors more than 120 years
      ago, their roles in cancer are often overlooked. This is puzzling given their
      potent immune modulatory, cytotoxic, and/or tissue repair capabilities, and
      recent studies demonstrating key roles for eosinophils in contexts far beyond
      their 'classical' field (e.g., metabolism, thermogenesis, and tissue
      regeneration). Recent data suggest that this frequently ignored cell is emerging
      as a potent immune effector and immune modulator in the tumor microenvironment.
      This review discusses the relevance of eosinophils to tumorigenesis and the
      potential to harness their function in cancer therapies.

PMID- 28741506
TI  - SASP: Tumor Suppressor or Promoter? Yes!
AB  - Cellular senescence is a permanent growth arrest in cells with damage or stress
      that could lead to transformation. Some tumor cells also undergo senescence in
      response to chemotherapy. Senescent cells secrete cytokines and other factors of
      the senescence-associated secretory phenotype (SASP) that contribute to tumor
      suppression by enforcing arrest and recruiting immune cells that remove these
      damaged or oncogene-expressing cells from organisms. However, some cells can
      develop a SASP comprising factors that are immunosuppressive and protumorigenic
      by paracrine mechanisms. Likewise, the SASP in treated cancers can either
      contribute to durable responses or drive relapse. Here, we discuss the studies
      that have demonstrated a complex and often conflicting role for the SASP in
      tumorigenesis and treatment response.

PMID- 28741507
TI  - mTOR Signaling Confers Resistance to Targeted Cancer Drugs.
AB  - Cancer is a complex disease and a leading cause of death worldwide. Extensive
      research over decades has led to the development of therapies that target cancer
      specific signaling pathways. However, the clinical benefits of such drugs are at
      best transient due to tumors displaying intrinsic or adaptive resistance. The
      underlying compensatory pathways that allow cancer cells to circumvent a drug
      blockade are poorly understood. We review here recent studies suggesting that
      mammalian TOR (mTOR) signaling is a major compensatory pathway conferring
      resistance to many cancer drugs. mTOR-mediated resistance can be cell-autonomous
      or non-cell-autonomous. These findings suggest that mTOR signaling should be
      monitored routinely in tumors and that an mTOR inhibitor should be considered as
      a co-therapy.

PMID- 28741508
TI  - A Molecular Take on Malignant Rhabdoid Tumors.
AB  - The molecular basis for the clinical heterogeneity observed in patients with
      malignant rhabdoid tumors is unknown. Recently, two reports revealed molecular
      intertumor heterogeneity in teratoid/rhabdoid tumors (ATRTs) and extra-cranial
      MRTs (ecMRTs) using genomic, transcriptomic, and epigenomic profiling. Distinct
      molecular subgroups were identified and new therapeutic targets were revealed.

PMID- 28741509
TI  - Probing Tumour Proteostasis and the UPR with Serum Markers.
AB  - Tumour proteostasis and the unfolded protein response (UPR) are emerging drivers
      of tumour progression and important determinants of clinical efficacy of cancer
      therapy. Recent findings indicate that they also regulate the production of
      protein tumour markers. Here, we discuss how this new knowledge opens up new
      perspectives for cancer therapeutics.

PMID- 28741510
TI  - Prolonging Reproductive Life after Cancer: The Need for Fertoprotective
      Therapies.
AB  - The survival rate of reproductive-age patients with cancer is increasing,
      reflecting the advent of better and more efficient therapies. Cancer survivors
      seek the resumption of a normal and healthy life, which often includes starting a
      family. Unfortunately, many cancer treatments increase the risk of premature
      ovarian insufficiency (POI) and infertility. Assisted reproductive technologies
      (ART) can address infertility, but fail to preserve the natural function of the
      ovaries as a source of hormones that regulate many aspects of women's health. The
      advancement of fertoprotective technologies is hindered by our lack of
      understanding of oocyte biology and their sensitivity to cancer therapies.
      Because many cancer treatments cause DNA damage, apoptosis is thought to be the
      major mechanism eliminating damaged oocytes. Indeed, recent studies in mice
      demonstrate that targeting proteins involved in apoptosis protects oocytes and
      prevents infertility in females exposed to radiation. Therefore, a better
      appreciation of oocyte response to radiation and anticancer drugs will uncover
      new targets for the development of specialized therapies to prevent ovarian
      failure. We make a case here for the necessity of such fertoprotective
      treatments. We review recent findings that have significantly advanced our
      understanding of how cancer therapies induce apoptotic death in oocytes, and how
      we could use this knowledge to design better fertoprotective treatments.

PMID- 28741511
TI  - Endoplasmic Reticulum Stress and the Hallmarks of Cancer.
AB  - Tumor cells are often exposed to intrinsic and external factors that alter
      protein homeostasis, thus producing endoplasmic reticulum (ER) stress. To cope
      with this, cells evoke an adaptive mechanism to restore ER proteostasis known as
      the unfolded protein response (UPR). The three main UPR signaling branches
      initiated by IRE1alpha, PERK, and ATF6 are crucial for tumor growth and
      aggressiveness as well as for microenvironment remodeling or resistance to
      treatment. We provide a comprehensive overview of the contribution of the UPR to
      cancer biology and the acquisition of malignant characteristics, thus
      highlighting novel aspects including inflammation, invasion and metastasis,
      genome instability, resistance to chemo/radiotherapy, and angiogenesis. The
      therapeutic potential of targeting ER stress signaling in cancer is also
      discussed.

PMID- 28741512
TI  - Re-Evaluating Clonal Dominance in Cancer Evolution.
AB  - Tumours are composed of genetically heterogeneous subclones which may diverge
      early during tumour growth. However, our strategies for treating and assessing
      outcome for patients are overwhelmingly based upon the classical linear paradigm
      for cancer evolution. Increasing numbers of studies are finding that minor
      subclones can determine clinical disease course, and that temporal and spatial
      heterogeneity needs to be considered in disease management. In this article we
      review evidence for cancer clonal heterogeneity, evaluating the importance of
      tumour subclones and their growth through both Darwinian and neutral evolution.
      Major shifts in current clinical practice and trial designs, aimed at
      understanding cancer evolution on a patient-by-patient basis, may be necessary to
      achieve more successful treatment of heterogeneous metastatic disease.

PMID- 28741513
TI  - Fingering the Correct Culprit: NonRANdom Target Selection for Therapy of
      Neuroblastoma.
AB  - Despite major advances in the genomics of neuroblastoma, high-risk patients still
      have considerable morbidity and mortality even with aggressive chemotherapy. In a
      recent article published in Cancer Cell, Schnepp et al. used an integrated
      genomic approach to identify the Ras-related nuclear protein (RAN) pathway as
      being integral in neuroblastoma pathogenesis and provided compelling validation
      for a role of the LIN28B-RAN-Aurora Kinase A (AURKA) pathway in neuroblastoma.
      This opens the door to less-toxic and more-effective therapy for high-risk
      neuroblastoma in the near future.

PMID- 28741514
TI  - Implications of Tumor Clonal Heterogeneity in the Era of Next-Generation
      Sequencing.
AB  - Recent whole-genome sequencing (WGS) studies have demonstrated that tumors
      typically comprise a founding clone and multiple subclones (i.e., clonal
      heterogeneity is common). The possible combination of mutations in each tumor
      clone is enormous, making each tumor genetically unique. Clonal heterogeneity
      likely has a role in cancer progression, relapse, metastasis, and chemoresistance
      due to functional differences in genetically unique subclones. In current
      clinical practice, gene mutations are only classified as being present or absent,
      ignoring the clonal complexity of cancers. In this review, we address how tumor
      clonality is measured using next-generation sequencing (NGS) data, highlight that
      clonal heterogeneity is common across multiple tumor types, and discuss the
      potential clinical implications of tumor clonal heterogeneity.

PMID- 28741515
TI  - Oncolytic Viruses: Exploiting Cancer's Deal with the Devil.
AB  - Tumor cells harbor tens to thousands of genetic and epigenetic alterations that
      disrupt cellular pathways, providing them with growth and survival advantages.
      However, these benefits come at a cost, with uncontrolled cell growth, defective
      apoptosis, sustained pathological angiogenesis, immune evasion, and a metastatic
      phenotype occurring at the expense of the antiviral response of the individual
      tumor cell. Oncolytic virotherapy is an emerging therapeutic strategy that uses
      replication-competent viruses to selectivity kill cancer cells by exploiting
      their impaired antiviral response. In this review, we outline our understanding
      of the alterations in signaling pathways that simultaneously contribute to the
      malignant phenotype and virus-mediated killing of cancer cells.

PMID- 28741516
TI  - Tissue-Specific Mutations in BRAF and EGFR Necessitate Unique Therapeutic
      Approaches.
AB  - A predominant number of cancers are driven by mutations of key growth signaling
      genes. While it might be expected that the same alterations within a given
      oncogene would be identified in all tissues, there are clear cases of tissue
      specificity. Here, we highlight the tissue specificity of BRAF and EGFR
      alterations and implications for therapeutic targeting.

PMID- 28741517
TI  - Filling the Gap on Caveolin-1 in Liver Carcinogenesis.
AB  - Caveolin-1 (CAV1) has emerged as a promoter of proliferation, metastasis, and
      chemoresistance in hepatoma cells, as well as a marker of poor prognosis in liver
      cancer. We discuss here current knowledge and future approaches to elucidating
      the molecular mechanisms underlying CAV1 action during hepatocarcinogenesis and
      evaluate its potential use in clinical therapies.

PMID- 28741518
TI  - Companion and Complementary Diagnostics: Clinical and Regulatory Perspectives.
AB  - Nearly 20 years ago, the US Food and Drug Administration (FDA) approved the first
      companion diagnostic assay and, today, this type of test governs the use of 18
      different drugs. With the appearance of PD-L1 immunohistochemistry (IHC) assays
      linked to the use of different PD-1/PD-L1 immune checkpoint inhibitors, a new
      class of predictive biomarker assays has emerged; the complementary diagnostics.
      These are predictive biomarker assays that aid the therapeutic decision process
      but are not a prerequisite for receiving a specific drug, as is the case with
      companion diagnostics. Both types of assay have the individual patient as a point
      of reference and they will be decisive for the move toward a more individualized
      pharmacotherapy. They are also considered important elements in the realization
      of precision medicine. Here, I discuss both companion and complementary
      diagnostics.

PMID- 28741520
TI  - Nutrient Exploitation within the Tumor-Stroma Metabolic Crosstalk.
AB  - The tumor microenvironment has an essential role in defining tumor malignancy,
      since it can either promote or prevent tumor initiation and subsequent
      progression and metastatic dissemination. Recent studies demonstrate that highly
      aggressive cancer cells display a high degree of metabolic plasticity paralleled
      by the acquisition of stemness and chemoresistant properties. In addition, cancer
      associated fibroblasts, endothelial cells, and immune cells have an important
      role in shaping the metabolic behavior of cancer cells. This review discusses the
      current knowledge of metabolic reprogramming in cancer, the tumor-stroma
      metabolic crosstalk, and the available compounds that may be used to effectively
      target the tumor-stroma metabolic symbiosis.

PMID- 28741521
TI  - Hypoxia-Inducible Factors: Master Regulators of Cancer Progression.
AB  - Intratumoral hypoxia (reduced O2 availability) is a common finding in human
      cancer and leads to increased activity of hypoxia-inducible factors (HIFs), which
      regulate the expression of genes that contribute to angiogenesis, metabolic
      reprogramming, extracellular matrix remodeling, epithelial-mesenchymal
      transition, motility, invasion, metastasis, cancer stem cell maintenance, immune
      evasion, and resistance to chemotherapy and radiation therapy. Conventional
      anticancer therapies target well-oxygenated and proliferating cancer cells,
      whereas there are no approved therapies that target hypoxic cancer cells, despite
      growing clinical and experimental evidence indicating that intratumoral hypoxia
      is a critical microenvironmental factor driving cancer progression. In this
      review, our current understanding of the consequences of HIF activity and the
      translational potential of targeting HIFs for cancer therapy are discussed.

PMID- 28741522
TI  - Karyotypic Aberrations in Oncogenesis and Cancer Therapy.
AB  - The propagation of whole-chromosome (aneuploid) or whole-genome (polyploid)
      defects is normally prevented by robust cell-intrinsic mechanisms. Moreover, non
      diploid cells are under strict immunological surveillance. Nonetheless, tumors
      contain a high percentage of non-diploid genomes, indicating that malignant cells
      acquire the ability to bypass these control mechanisms and obtain a
      survival/proliferation benefit from bulky karyotypic defects. The non-diploid
      state imposes a significant metabolic burden on cancer cells and hence can be
      selectively targeted for therapeutic purposes. Here we discuss the impact of
      abnormal karyotypes on oncogenesis, tumor progression, and response to treatment,
      focusing on the biochemical and metabolic liabilities of non-diploid cells that
      can be harnessed for the development of novel chemo(immuno)therapeutic regimens
      against cancer.

PMID- 28741523
TI  - Micronutrients: A Double-Edged Sword in Microbe-Induced Gastric Carcinogenesis.
AB  - Epidemiologic studies throughout the world have uniformly demonstrated
      significant relationships between the intake of dietary micronutrients and
      gastric cancer risk. An exciting concept that has recently gained considerable
      traction is that micronutrients modulate gene expression within Helicobacter
      pylori, the strongest identified risk factor for gastric carcinogenesis. We
      present evidence here that essential micronutrients have a direct effect on H.
      pylori virulence, which subsequently affects interactions at the host-pathogen
      interface, thereby facilitating the development of premalignant and malignant
      lesions in the stomach. Further, these fundamental concepts provide a framework
      for understanding mechanisms driving the development of other malignancies that
      arise from foci of gastrointestinal inflammation.

PMID- 28741524
TI  - Cancer-Associated Fibroblasts: Perspectives in Cancer Therapy.
AB  - The interplay between cancer cells and stromal cells is increasingly recognized
      as a main driver of tumor progression and metastasis. This Forum article
      highlights the role of cancer-associated stromal fibroblasts (CAFs) in
      tumorigenesis and discusses the potential for developing specific stromal cancer
      therapies.

PMID- 28741525
TI  - Fibrosis and Cancer: Partners in Crime or Opposing Forces?
AB  - The relation between fibrosis and cancer has long been debated, specifically
      whether desmoplasia precedes, accompanies, or succeeds tumourigenesis,
      progression, and metastasis. Recent reports have published opposing data, adding
      to the perplexity. However, what is emerging is that it is likely the specific
      properties of the extracellular matrix (ECM) that determine the paradoxical
      nature of cancer-associated fibrosis.

PMID- 28741526
TI  - GNAS Mutations: Drivers or Co-Pilots? Yet, Promising Diagnostic Biomarkers.
AB  - Over 25 years ago, GNAS mutations were discovered associated with McCune-Albright
      syndrome (MAS) and pituitary tumors. The mutant gene, encoding the heterotrimeric
      Gs protein, was named 'derived from Gs Protein' (gsp) oncogene. For a long time,
      gsp remained associated with specific endocrine tumors. Recently, high
      frequencies of gsp were reported for a rapidly growing number of neoplasms in the
      gastrointestinal tract. Will heterotrimeric G-proteins follow small G-proteins
      and become recognized as cancer biomarkers and therapeutic targets?

PMID- 28741528
TI  - Biomarkers in Melanoma: Lessons from Translational Medicine.
AB  - The treatment landscape for advanced melanoma has been rapidly evolving. As new
      therapies become available, there is a need for better biomarkers to detect
      disease, guide patient selection, and monitor for response. The use of tumor
      genetics has been able to predict responses to targeted therapy in melanoma.
      However, the role of biomarkers in melanoma detection, monitoring, and
      immunotherapy has been less successful and is still being defined. Translational
      studies in many areas of melanoma are being performed to identify biomarkers and
      validate their clinical role. In this review, we examine the status of biomarkers
      in melanoma and areas of future development.

PMID- 28741527
TI  - Hypoxia: Signaling the Metastatic Cascade.
AB  - Hypoxia is a potent microenvironmental factor that promotes tumor metastasis.
      Recent studies have revealed mechanisms by which hypoxia and activation of
      hypoxia inducible factor (HIF)-dependent signaling promotes metastasis through
      the regulation of metabolic reprogramming, the stem cell phenotype, invasion,
      angiogenesis, immune suppression, the premetastatic niche, intravasation and/or
      extravasation, and resistance to apoptosis. These discoveries suggest novel
      paradigms in tumor metastasis and identify new opportunities for therapeutic
      intervention in the prevention and treatment of metastatic disease. Here, we
      review the impact of hypoxia and hypoxic signaling pathways in tumor and stromal
      cells on each step of the metastatic cascade.

PMID- 28741529
TI  - Amphiregulin in Cancer: New Insights for Translational Medicine.
AB  - Although there is a large body of literature regarding amphiregulin (AREG) in
      human cancer, most knowledge focuses on its cell-autonomous functions in
      epithelial malignancies. Recent studies revealed that AREG is also present in the
      tumor microenvironment (TME) and contributes to therapeutic resistance. We
      discuss emerging concepts of AREG tumor biology and highlight their implications
      for translational medicine.

PMID- 28741530
TI  - Compromised Telomeric Heterochromatin Promotes ALTernative Lengthening of
      Telomeres.
AB  - Alternative lengthening of telomeres (ALT) is an enigmatic process that allows
      certain cancers to maintain telomeres in the absence of telomerase. ALT cancers
      are frequently defective for ATRX/DAXX, a chaperone complex that deposits histone
      variant H3.3 at telomeres. We propose that mutations in alpha thalassemia-mental
      retardation syndrome X-linked (ATRX)/death-domain associated protein (DAXX) prime
      ALT activation by disrupting telomeric heterochromatin.

PMID- 28741531
TI  - Molecular Discriminators of Racial Disparities in Prostate Cancer.
AB  - Recent molecular characterization of prostate cancer (PCa) identified novel
      genetic aberrations and disease subtypes. The frequencies of molecular
      aberrations show racial disparity. Clinical strategies and targeted therapies
      embracing these racial differences are required. Here we discuss ethnic
      differences in genetic alterations and their impact on the susceptibility,
      progression, and treatment of prostate cancer.

PMID- 28741532
TI  - The Immune Biology of Microsatellite-Unstable Cancer.
AB  - Deficient DNA mismatch repair (MMR) boosts the accumulation of frameshift
      mutations in genes encompassing coding microsatellites (cMS). This results in the
      translation of proteins with mutation-induced frameshift peptides (neoantigens)
      rendering microsatellite-unstable (MSI) cancers highly immunogenic. MSI cancers
      express a defined set of neoantigens resulting from functionally relevant driver
      mutations, which are shared by most MSI cancers. Patients with MSI cancers and
      healthy individuals affected by Lynch syndrome, an inherited predisposition for
      MSI cancers, develop specific immune responses against these neoantigens. In this
      review, we summarize our current understanding of the immune biology of MSI
      cancers and outline new concepts and research directions to develop not only
      therapeutic treatments, but also preventive vaccines based on the MSI cancer
      genome landscapes.

PMID- 28741533
TI  - Gender Dimorphism Creates Divergent Cancer Susceptibilities.
AB  - To date, the cellular and molecular mechanisms underlying sexual dimorphism in
      the incidence, prognosis, and treatment responses of cancer remain unclear. In a
      recent article published in Cancer Cell, Yuan et al. applied a pan-cancer
      analysis to identify sex-biased molecular signatures and revealed two sex-effect
      groups characterized by distinct incidence and mortality profiles.

PMID- 28741534
TI  - Tumor-Stromal Cell Communication: Small Vesicles Signal Big Changes.
AB  - Reciprocal interactions between malignant and stromal cells create a local
      microenvironment that fosters tumor growth. Extracellular vesicles (EVs) such as
      exosomes, microvesicles, and large oncosomes are involved in tumor-stroma
      communication by shuttling signaling cargo and other molecules. Here we discuss
      how EVs released by cancer or stromal cells impact the proliferation,
      differentiation, and metabolism of tumors.

PMID- 28741535
TI  - Cancer Exosomes as miRNA Factories.
AB  - miRNAs modulate gene expression while exosomes are extracellular cargo vessels
      that transport miRNAs and other materials to surrounding cells. When exosomes are
      taken up by recipient cells, the released miRNAs can modulate immune responses,
      inhibit apoptosis, and promote angiogenesis to maintain tumor growth. Central to
      this regulation is the processing of the primary transcripts into active miRNAs,
      which occurs exclusively within mammalian cells. Challenging this dogma is the
      discovery that Dicer and Ago2, key components of miRNA processing, are also
      present inside exosomes. While the exact nature of this processing requires
      extensive proof, it is an exciting notion that exogenous miRNA factories could
      exist outside the canonical boundaries of mammalian cells.

PMID- 28741536
TI  - Brain Metastasis: Clinical Implications of Branched Evolution.
AB  - Brain metastases (BM) are the most common intracranial tumor in adults. An
      improved understanding of the genomic architecture of cancers has facilitated a
      transition from chemotherapy to genotype-guided treatment approaches. Although
      this shift has translated into improved extracranial disease control and patient
      outcomes, progression of BM is still a common occurrence. In this review we
      provide an overview of the current understanding of intermetastatic genomic
      heterogeneity, summarize the spectrum of genetic alterations detected in BM, and
      discuss how molecular profiling of BM can create opportunities for refining
      therapeutic strategies to not only minimize the morbidity from progression of BM
      but potentially also improve outcomes.

PMID- 28741537
TI  - Actionable Molecular Biomarkers in Primary Brain Tumors.
AB  - Recent genome-wide studies of malignancies of the central nervous system (CNS)
      have revolutionized our understanding of the biology of these tumors. This newly
      gained knowledge provides a wealth of opportunity for biomarker-driven clinical
      research. To date, however, only few of the available molecular markers truly
      influence clinical decision-making and treatment. The most widely validated
      markers in neuro-oncology presently are: (i) MGMT promoter methylation as a
      prognostic and predictive marker in glioblastoma; (ii) codeletion of 1p and 19q
      differentiating oligodendrogliomas from astrocytomas; (iii) IDH1/2 mutations; and
      (iv) select pathway-associated mutations. This article focuses on currently
      impactful biomarkers in adult and pediatric brain cancers and it provides a
      perspective on the direction of research in this field.

PMID- 28741538
TI  - Cholera in Yemen: war, hunger, disease...and heroics.

PMID- 28741539
TI  - Corrections.

PMID- 28741540
TI  - Whither "latent"?

PMID- 28741541
TI  - Denying access to bedaqualine in India costs lives.

PMID- 28741542
TI  - 23-valent pneumococcal polysaccharide vaccine against pneumococcal pneumonia.

PMID- 28741543
TI  - Developing new insecticides to prevent chaos: the real future threat.

PMID- 28741544
TI  - Syphilis trends in China: biased by screening and reporting?

PMID- 28741545
TI  - Zika virus infection and microcephaly in Vietnam.

PMID- 28741546
TI  - Surveillance of Crimean-Congo haemorrhagic fever in Pakistan.

PMID- 28741547
TI  - Highlights from the fourth ICPIC.

PMID- 28741548
TI  - Nigeria battles infection on several fronts.

PMID- 28741551
TI  - Disseminated aspergillosis in an HIV-positive cannabis user taking steroid
      treatment.

PMID- 28741552
TI  - Intrinsic versus Extrinsic Cancer Risks: The Debate Continues.
AB  - Deciphering the relative contribution of intrinsic (e.g., genetic) and extrinsic
      (e.g., life style, environmental) risk factors in cancer development is crucial
      for strategizing cancer prevention. The recent publication by Wu and colleagues
      in Nature appears as an important contribution to the debate previously initiated
      by Tomasetti and Vogelstein in Science, who proposed that two-thirds of cancers
      can be attributed to random mutations and hence 'bad luck'. By contrast, Wu and
      colleagues, using four lines of evidence, suggest that cancer risk is dominated
      by extrinsic factors, and intrinsic risk factors only contribute marginally. The
      debate remains open, and an approach focusing on the evolutionary ecology of
      organs could provide crucial insights.

PMID- 28741553
TI  - Signaling by Extracellular Vesicles Advances Cancer Hallmarks.
AB  - Mammalian cells secrete various extracellular vesicles (EVs; exosomes,
      microvesicles, and apoptotic bodies) that differ in biogenesis, composition, and
      function. Each vesicle type can originate from normal or cancerous cells,
      transfer molecular cargo to both neighboring and distant cells, and modulate
      cellular behaviors involved in eubiology and pathology, such as tumor
      development. Here, we review evidence for the role of EVs in the establishment
      and maintenance of cancer hallmarks, including sustaining proliferative
      signaling, evading growth suppression, resisting cell death, reprogramming energy
      metabolism, acquiring genomic instability, and remodeling the tumor
      microenvironment. We also discuss how EVs are implicated in the induction of
      angiogenesis, control of cellular invasion, initiation of premetastatic niches,
      maintenance of inflammation, and evasion of immune surveillance. The deeper
      understanding of the biology of EVs and their contribution to the development and
      progression of tumors is leading to new opportunities in the diagnosis and
      treatment of cancer.

PMID- 28741555
TI  - Karen Vousden: Complexities of Tumor Suppression.

PMID- 28741554
TI  - Welcome to Trends in Cancer.

PMID- 28741556
TI  - Craig Thompson: Fueling Cancer.

PMID- 28741557
TI  - Anton Berns: Modeling Cancer.

PMID- 28741558
TI  - Cellular Mechanisms Underlying Intertumoral Heterogeneity.
AB  - Intertumoral heterogeneity is driven by a combination of intrinsic and extrinsic
      mechanisms. Intrinsic mechanisms include the genetic/epigenetic mutational
      profile of cells and the nature of the 'cell of origin'. There is accumulating
      evidence that distinct 'cells of origin' within an organ can give rise to
      different subtypes of cancer. Tissue-specific stem and progenitor cells are the
      predominant targets exploited for tumor initiation. Extrinsic factors imposed by
      the microenvironment may also directly influence the cell of origin by eliciting
      dedifferentiation. Identification of these target cell populations is important
      for earlier diagnosis, the detection of premalignant clones during relapse, and
      the design of prevention therapies for high-risk cancer families. Here we review
      recent developments in deciphering the cellular origins of solid cancers.

PMID- 28741559
TI  - Douglas Lowy: Precision Medicine Gets Presidential Treatment.

PMID- 28741560
TI  - Cancer Genomics in Clinical Context.
AB  - Precision medicine requires appropriate application of genomics in clinical
      practice. In cancer, we have witnessed practice-changing examples of how genomic
      knowledge is translated into more tailored and effective therapies. The next
      opportunity is to embed cancer genomics in clinical context so that patient
      centric longitudinal clinical, genomic, and molecular phenotypes can be compiled
      for adaptive learning between precision medicine research and clinical care with
      the goal of accelerating clinically-actionable discoveries. We describe here an
      adaptive learning platform, APOLLOTM (adaptive patient-oriented longitudinal
      learning and optimization) designed to integrate genomic research in the context
      of, but not in the path of, routine and investigational clinical care for
      purposes of enabling data-driven discovery across disciplines such that every
      patient can contribute to and potentially benefit from research discoveries.

PMID- 28741561
TI  - Robert Weinberg: Beyond Hallmarks.

PMID- 28741562
TI  - En Route to Metastasis: Circulating Tumor Cell Clusters and Epithelial-to
      Mesenchymal Transition.
AB  - Blood-borne metastasis accounts for the vast majority of cancer-related deaths
      and it is fueled by the generation of circulating tumor cells (CTCs) from a
      primary tumor deposit. Recent technological advances have made it possible to
      characterize human CTCs as they travel within the bloodstream. CTCs are found
      both as single cells and as clusters of cells held together by intercellular
      junctions. Although less prevalent, CTC clusters appear to have greater
      metastatic potential than single CTCs in the circulation. Both may exhibit shifts
      in expression of epithelial and mesenchymal markers, which may show dynamic
      changes during cancer progression. In this review we discuss recent insights into
      the biological properties of individual and clustered cancer cells in the
      circulation.

PMID- 28741563
TI  - Mina J. Bissell: Context Matters.

PMID- 28741564
TI  - Surviving at a Distance: Organ-Specific Metastasis.
AB  - The clinical manifestation of metastasis in a vital organ is the final stage of
      cancer progression and the main culprit of cancer-related mortality. Once
      established, metastasis is devastating, but only a small proportion of the cancer
      cells that leave a tumor succeed at infiltrating, surviving, and ultimately
      overtaking a distant organ. The bottlenecks that challenge cancer cells in newly
      invaded microenvironments are organ-specific and consequently demand distinct
      mechanisms for metastatic colonization. We review the metastatic traits that
      allow cancer cells to colonize distinct organ sites.

PMID- 28741565
TI  - Peter Jones: Leaving a Mark on the Cancer Genome.

PMID- 28741566
TI  - Suzanne Topalian: Unleashing the Immune System to Fight Cancer.

PMID- 28741567
TI  - Metastasis: Circulating Tumor Cells in Small Cell Lung Cancer.
AB  - Small cell lung cancer (SCLC) is distinguished by excessive numbers of
      circulating tumor cells (CTCs) in extended and recurring disease. This malignancy
      has a poor prognosis due to rapid emergence of chemoradioresistant relapses after
      first-line chemotherapy. In vitro expansion of several CTC lines allowed for a
      detailed study of the contribution of these cells to metastasis. Generation of
      CTCs involves the establishment of co-cultures and recruitment of macrophages and
      specific cytokines. All cell lines show E-cadherin-positive epithelial-like cells
      and spontaneous assembling into very large tumorospheres. Such multicellular
      aggregates seem to be responsible for the observed broad resistance due to
      limited access to drugs, quiescent cell layers, and hypoxic cores.

PMID- 28741568
TI  - Genetic Redundancy, Functional Compensation, and Cancer Vulnerability.
AB  - Cancer genomes acquire somatic alterations that largely differ between and within
      cancer types. Several of these alterations inactivate genes that are normally
      functional with no deleterious consequences on cancer cells due to genetic
      redundancy. Here we discuss how this leads to cancer synthetic dependencies that
      can be exploited in therapy.

PMID- 28741569
TI  - Melanoma, Viagra, and PDE5 Inhibitors: Proliferation and Metastasis.
AB  - Inhibitors of the cGMP-degrading phosphodiesterase (PDE) 5 have achieved
      blockbuster status in the treatment of penile erectile dysfunction (PED). Their
      repurposing is currently being proposed to treat certain solid tumours and
      various other diseases. In cruel irony, however, it appears from recent clinical
      studies that PDE5 inhibitors may increase the risk of malignant melanoma by
      negating newly identified brakes on proliferation and metastasis provided by
      PDE5A.

PMID- 28741570
TI  - Thermoneutrality, Mice, and Cancer: A Heated Opinion.
AB  - The 'mild' cold stress caused by standard sub-thermoneutral housing temperatures
      used for laboratory mice in research institutes is sufficient to significantly
      bias conclusions drawn from murine models of several human diseases. We review
      the data leading to this conclusion, discuss the implications for research and
      suggest ways to reduce problems in reproducibility and experimental transparency
      caused by this housing variable. We have found that these cool temperatures
      suppress endogenous immune responses, skewing tumor growth data and the severity
      of graft versus host disease, and also increase the therapeutic resistance of
      tumors. Owing to the potential for ambient temperature to affect energy
      homeostasis as well as adrenergic stress, both of which could contribute to
      biased outcomes in murine cancer models, housing temperature should be reported
      in all publications and considered as a potential source of variability in
      results between laboratories. Researchers and regulatory agencies should work
      together to determine whether changes in housing parameters would enhance the use
      of mouse models in cancer research, as well as for other diseases. Finally, for
      many years agencies such as the National Cancer Institute (NCI) have encouraged
      the development of newer and more sophisticated mouse models for cancer research,
      but we believe that, without an appreciation of how basic murine physiology is
      affected by ambient temperature, even data from these models is likely to be
      compromised.

PMID- 28741572
TI  - Intravital Insights into Heterogeneity, Metastasis, and Therapy Responses.
AB  - Tumor progression is driven by a series of genetic and microenvironmental
      changes. These events lead to heterogeneous tumors which consist of a variety of
      cells from which some cells may possess properties which promote survival after
      therapy and metastasis. Recent advances in intravital microscopy (IVM) have
      enabled visualization of this tumor heterogeneity over time at a single-cell
      resolution. We highlight here the latest IVM studies that have revealed the
      dynamic interactions between the tumor cells and their local microenvironment. We
      review the most recent data that exposes how these dynamic interactions cause an
      additional increase in tumor heterogeneity, resulting in multiple metastatic
      strategies and facilitating therapy resistance.

PMID- 28741573
TI  - Novel radiation dose reduction fluoroscopic technology facilitates chronic total
      occlusion percutaneous coronary interventions.
AB  - AIMS: Radiation exposure and prolonged procedure time continue to limit the
      complexity of CTO-PCI procedures attempted. This study aimed to assess the impact
      of radiation dose-limiting equipment on radiation dosage and fluoroscopic time in
      chronic total occlusion (CTO) percutaneous coronary interventions (PCI). METHODS
      AND RESULTS: Retrospective clinical and dosimetric data from diagnostic
      catheterisations (DXC) and CTO-PCI procedures performed on one of three variants
      of interventional fluoroscopic equipment were collected. Fluoroscopic time, air
      kerma, kerma area product and contrast utilisation were stratified by procedure
      type and compared among equipment types. To standardise comparisons among
      equipment configurations, an efficiency index (EI) was calculated. In total,
      2,947 DXC and 276 CTO-PCI procedures were studied. For DXC, radiation dose (AK)
      decreased by 45% (despite modest increases in fluoroscopic time [FT]) between the
      reference (REF) and moderately dose-optimised (ECO) machines. A further 20%
      decrease in AK was observed on the highly dose-optimised machine (CLA). For CTO
      PCI, AK declined by almost half (48%), despite a 76% increase in FT and higher
      procedural success rates (69.8% versus 83.0%) between REF and CLA. * Conclusions:
      Novel dose-optimised fluoroscopic equipment allows longer FT with a decrease in
      radiation dose to both patient and operator. This should allow operators to
      undertake increasingly longer and more complex procedures and reduce operators'
      lifetime irradiation.

PMID- 28741571
TI  - RP-MDM2-p53 Pathway: Linking Ribosomal Biogenesis and Tumor Surveillance.
AB  - Ribosomal biogenesis is tightly associated with cellular activities, such as
      growth, proliferation, and cell cycle progression. Perturbations in ribosomal
      biogenesis can initiate so-called nucleolar stress. The process through which
      ribosomal proteins (RPs) transduce nucleolar stress signals via MDM2 to p53 has
      been described as a crucial tumor-suppression mechanism. In this review we focus
      on recent progress pertaining to the function and mechanism of RPs in association
      with the MDM2-p53 tumor-suppression network, and the potential implications this
      surveillance network has for cancer development.

PMID- 28741574
TI  - Prediction of left ventricular dysfunction after device closure of patent ductus
      arteriosus: proposal for a new functional classification.
AB  - AIMS: The aims of this study were to determine the incidence and correlates of
      left ventricular (LV) dysfunction amongst percutaneous patent ductus arteriosus
      (PDA) device closure patients, and to propose an indexed parameter for predicting
      LV dysfunction. METHODS AND RESULTS: In a retrospective cross-sectional analysis
      of 30 months duration, 447 patients who underwent PDA device closure were
      studied. The diameter of the PDA at the pulmonary artery end was measured in the
      angiograms in all patients and was indexed for their body surface area. The
      indexed PDA size was categorised into group A (1-2.9 mm/m2, 35/447), B (3-5.9
      mm/m2, 254/447), C (6-8.9 mm/m2, 66/447) and D (>9 mm/m2, 35/447). Systolic LV
      function was evaluated using echocardiography at frequent intervals. Overall,
      62.63% of the patients were female (280/447). At baseline, all 447 patients had
      normal LV function. LV dysfunction was seen in 102/447 (22.8%) patients with 2.8%
      in category A (1/35), 10.6% in category B (27/254), 34.1% in category C (42/123)
      and 91.4% in category D (32/35) after PDA device closure. Correlation of indexed
      PDA size and LV dysfunction was statistically significant (p<0.05). CONCLUSIONS:
      Accurate prediction of LV dysfunction is important in risk stratification, ICU
      management and counselling in PDA device closures. Indexed PDA size correlates
      well with post-procedural LV dysfunction. The authors propose a new
      classification of PDA utilising this accurate, reproducible and easy to perform
      parameter, which does not involve any extra cost, for risk stratification and
      early management in device closure of PDA.

PMID- 28741575
TI  - The drug-eluting resorbable magnesium vascular scaffold in complex coronary
      bifurcations: insights from an in vivo multimodality imaging study.
AB  - AIMS: This acute in vivo study sought to provide insights regarding the
      feasibility of performing complex bifurcation stenting with Magmaris magnesium
      alloy bioresorbable scaffolds (Biotronik, Bulach, Switzerland). METHODS AND
      RESULTS: Twenty-five New Zealand White rabbits underwent stenting of non-diseased
      aorto-iliac bifurcations with the Magmaris using provisional (PS; n=5), culotte
      (n=6), modified T (n=6), or T and protrusion (TAP, n=8) stenting techniques.
      Angiography, optical coherence tomography and micro-computed tomography were
      performed. Angiographic results were good without evidence of side branch (SB)
      compromise. In 9/25 procedures, strut fractures were identified with minimal
      luminal compromise in two cases. PS opened the SB optimally without evidence of
      scaffold compromise. Culotte resulted in complete bifurcation coverage and good
      scaffold expansion; single strut fractures were present in three out of six and
      double fractures in one out of six procedures. Modified T and TAP resulted in
      complete bifurcation coverage, minimal neocarina double-strut layers and good
      expansion. In two out of six modified T procedures, strut fractures were present
      with SB scaffold deformity present in an additional two out of six procedures. In
      three out of eight TAP procedures, strut fractures were present without
      compromising overall scaffold integrity. CONCLUSIONS: Bifurcation stenting using
      Magmaris appears feasible. PS with additional TAP whenever needed seems a
      reasonable approach. Whenever a two-stent technique is planned, TAP appears most
      favourable whilst modified T and culotte stenting should probably be avoided.

PMID- 28741576
TI  - A randomised comparison of biodegradable polymer- and permanent polymer-coated
      platinum-chromium everolimus-eluting coronary stents in China: the EVOLVE China
      study.
AB  - AIMS: The EVOLVE China randomised study sought to evaluate the clinical safety
      and effectiveness of the SYNERGY bioabsorbable polymer-coated everolimus-eluting
      stent (EES) for the treatment of patients with coronary heart disease in China.
      METHODS AND RESULTS: Eligible patients with de novo native coronary artery
      lesions were randomised (1:1) to receive the SYNERGY or PROMUS Element Plus
      stent. The primary endpoint was in-stent late loss at nine months. Secondary
      endpoints included death, MI, revascularisation, and stent thrombosis up to 12
      months. A total of 412 subjects were randomised (205 SYNERGY; 207 PROMUS Element
      Plus) at 14 sites in China from October 2013 to July 2014. SYNERGY was non
      inferior to PROMUS Element Plus for the primary endpoint of nine-month in-stent
      late loss: SYNERGY 0.20+/-0.33 mm vs. PROMUS Element Plus 0.17+/-0.38 mm with an
      upper one-sided 97.5% confidence interval of the difference (0.10 mm),
      significantly less than the non-inferiority margin (0.15 mm; p<0.0008). Clinical
      adverse event rates were low and not significantly different between groups at
      nine and 12 months (all p>0.05). CONCLUSIONS: In the EVOLVE China trial, the
      SYNERGY bioabsorbable polymer-coated EES was noninferior to the PROMUS Element
      Plus permanent polymer-coated EES for the primary endpoint of late loss at nine
      months.

PMID- 28741577
TI  - Comparison of new-generation renal artery denervation systems: assessing lesion
      size and thermodynamics using a thermochromic liquid crystal phantom model.
AB  - AIMS: The aim of this study was to evaluate and compare lesion dimensions and
      thermodynamics of the new-generation multi-electrode Symplicity Spyral and the
      new-generation multi-electrode EnligHTN renal artery denervation systems, using a
      thermochromic liquid crystal phantom model. METHODS AND RESULTS: A previously
      described renal artery phantom model was used as a platform for radiofrequency
      ablation. A total of 32 radiofrequency ablations were performed using the multi
      electrode Symplicity Spyral (n=16) and the new-generation EnligHTN systems
      (n=16). Both systems were used as clinically recommended by their respective
      manufacturer. Lesion borders were defined by the 51 degrees C isotherm. Lesion
      size (depth and width) was measured and compared between the two systems. Mean
      lesion depth was 2.15+/-0.02 mm for the Symplicity Spyral and 2.32+/-0.02 mm for
      the new-generation EnligHTN (p-value <0.001). Mean lesion width was 3.64+/-0.08
      mm and 3.59+/-0.05 mm (p-value=0.61) for the Symplicity Spyral and the new
      generation EnligHTN, respectively. CONCLUSIONS: The new-generation EnligHTN
      system produced lesions of greater depth compared to the Symplicity Spyral under
      the same experimental conditions. Lesion width was similar between both systems.
      Achieving greater lesion depth by use of the new-generation EnligHTN may result
      in better efficacy of renal artery denervation.

PMID- 28741578
TI  - Paclitaxel-eluting stents versus everolimus-eluting coronary stents in a diabetic
      population: two-year follow-up of the TUXEDO-India trial.
AB  - AIMS: The aim of this study was to report whether the superiority of the
      everolimus-eluting stent (EES) vs. the paclitaxel-eluting stent (PES) at one-year
      follow-up in the Taxus Element versus Xience Prime in a Diabetic Population
      (TUXEDO)-India trial was sustained at longer-term follow-up. METHODS AND RESULTS:
      One thousand eight hundred and thirty (1,830) patients with diabetes mellitus and
      coronary artery disease were randomised to EES vs. PES. Follow-up data up to two
      years were available in 1,701 (92.9%) patients. The primary endpoint was target
      vessel failure (TVF), defined as the composite of cardiac death, target vessel
      myocardial infarction (TV-MI), or ischaemia-driven target vessel
      revascularisation (TVR). Treatment with EES had a lower two-year rate of TVF
      (4.3% vs. 6.6%, p=0.03). Of the secondary endpoints, EES significantly reduced
      any MI (1.6% vs. 3.5%, p=0.01), TV-MI (0.7% vs. 3.1%, p=0.0001), ST (0.4% vs.
      2.2%, p=0.001), cardiac death or target vessel MI (2.9% vs. 4.8%, p=0.04) and TLR
      (1.9% vs. 3.7%, p=0.02), compared with PES. Between one year and two years, no
      significant differences in the clinical outcomes were observed (pinteraction
      >0.05). CONCLUSIONS: In this adequately powered trial, the benefits of EES vs.
      PES in a diabetic population seen at one year were maintained at two years.

PMID- 28741579
TI  - Subclinical leaflet thickening and stent frame geometry in self-expanding
      transcatheter heart valves.
AB  - AIMS: This study aimed to assess the potential relationship between subclinical
      leaflet thickening and stent frame geometry in patients who underwent aortic
      valve replacement with a self-expanding transcatheter heart valve (THV). METHODS
      AND RESULTS: Seventy-five patients with a self-expanding THV were studied with 4D
      computed tomography and analysed for leaflet thickening. There was no difference
      in THV size, overall THV expansion, eccentricity or implantation depth between
      patients with and those without leaflet thickening. Moderate-to-severe regional
      THV underexpansion (<=90 degrees ) more frequently occurred at the non-coronary
      and right coronary cusps with a significantly higher incidence of leaflet
      thickening than in cases of full regional THV expansion (24% vs. 3%, p<0.01).
      Regional THV underexpansion at the inflow level more often translated into the
      same issue at the valvular level in THV with intra-annular as compared to supra
      annular valve position (54% vs. 17%; p=0.04). In case of post-dilatation,
      regional THV underexpansion occurred less frequently as compared to THV that were
      not post-dilated (18% vs. 43%, p=0.028). A similar but non-significant trend was
      found for leaflet thickening. CONCLUSIONS: Regional THV stent frame
      underexpansion is associated with an increased risk of leaflet thickening. Post
      dilatation of self-expanding THV as well as a supra-annular valve position seem
      to reduce the occurrence of this phenomenon.

PMID- 28741580
TI  - Individualised decision-making.

PMID- 28741581
TI  - Regret about the decision to start dialysis: a cross-sectional Dutch national
      survey.
AB  - BACKGROUND: More older patients with end-stage renal disease (ESRD) are starting
      dialysis. Elderly patients often prefer treatments that focus on quality of life
      rather than primarily extending life and a substantial group of elderly dialysis
      patients might regret their decision to start dialysis. Healthcare provider and
      patient-related factors may be involved. Our objective was to measure the
      percentage of patients in the Netherlands who regretted their decision to start
      dialysis. METHODS: Cross-sectional Dutch national survey of dialysis patients. A
      short questionnaire about age, satisfaction with pre-dialysis education, present
      treatment, dialysis initiation, regret about decision to start dialysis and key
      figures in decision-making was developed. RESULTS: A total of 1371 questionnaires
      were returned for analysis from 28 dialysis units. Of the patients 7.4% regretted
      their decision to start dialysis, 50.5% reported the nephrologist's opinion to be
      crucial in decision-making and these patients experienced more regret than those
      who made the decision themselves (odds ratio, OR: 1.81). When family influenced
      decision-making more regret was experienced compared with those who decided
      themselves (OR: 2.73). Older age was associated with less regret (p = 0.02) and
      higher treatment satisfaction (p < 0.001); 52.8% of participants described
      dialysis initiation as being sudden. CONCLUSION: The majority of patients did not
      regret their decision to start dialysis. Older patients were more satisfied with
      their treatment and felt less regret. The nephrologist's and the family's opinion
      were directional in decision-making on ESRD treatment options and were associated
      with more regret, especially in younger patients.

PMID- 28741582
TI  - Prevalence of drug-drug interactions in the era of HIV integrase inhibitors: a
      retrospective clinical study.
AB  - BACKGROUND: Antiretroviral agents pose a high risk for drug-drug interactions
      (DDIs), mainly but not limited to being a substrate, inducer or inhibitor of P450
      cytochrome enzymes. In part metabolised by other pathways, integrase inhibitors
      might show a more favourable profile. The aim of this study was to investigate
      the prevalence of DDIs in daily clinical practice for patients starting different
      antiretroviral treatment (ART) regimens. METHODS: All patients starting ART in
      our centre from January 2009 to April 2016 were included. All prescribed co
      medications since the start of ART were recorded retrospectively from the medical
      files and screened for DDIs using the Liverpool HIV drug interaction database.
      Only DDIs between antiretroviral and non-antiretroviral drugs were considered.
      RESULTS: We included 145 patients, of which 42% were on an integrase inhibitor
      based regimen, mainly dolutegravir and elvitegravir. Of the patients, 78% (n =
      113) took co-medication. Potential DDIs were seen in 63% of the patients with co
      medication; contraindicated prescriptions were detected in 1%. Protease inhibitor
      based ART was a risk factor for DDI (odds ratio (OR) 2.57; 95% confidence
      interval (CI) 1.06-6.19), in contrast to non-nucleoside reverse transcriptase
      inhibitor-based ART (OR 0.77; 95% CI 0.32-1.84). Concerning integrase inhibitors,
      a significantly lower risk was seen with dolutegravir-based treatment (OR 0.35;
      95% CI 0.15-0.82), though not for elvitegravir-based ART (OR 2.51; 95% CI 0.66
      9.58). CONCLUSIONS: ART regimens pose a dissimilar risk for drug-drug
      interactions in clinical practice. Regarding the use of integrase inhibitors, a
      significantly lower risk was seen with dolutegravir-based treatment.

PMID- 28741583
TI  - Elderly patients with an atypical presentation of illness in the emergency
      department.
AB  - BACKGROUND: Very little information is available on the prevalence and clinical
      outcome of elderly patients with atypical presentations of illness in the
      emergency department. The objective was to determine the prevalence and clinical
      outcome of elderly patients seen in the emergency department with an atypical
      presentation. METHODS: A monocentric retrospective observational study on 355
      elderly patients presenting to the emergency department. Patients of 80 years and
      older were included. Data were extracted from the electronic medical file.
      RESULTS: A total of 355 patients were included, with a mean age of 86 years; 53%
      of these elderly patients had an atypical presentation of illness. Mostly this
      was due to a fall (71%). A total of 15% of the patients with an atypical
      presentation reported no specific symptoms of the underlying disease. Patients
      with atypical presentation were more likely to have a longer stay in hospital (p
      < 0.001), to be discharged to a care institution (p = 0.000), and to have a
      higher delirium observation score (p < 0.001). There was no significant
      difference in one-year survival (p = 0.056). CONCLUSION: Atypical presentation of
      illness in elderly patients is highly prevalent in the emergency department.
      Falling accidents are the most important reason for this. Patients with an
      atypical presentation have a worse clinical outcome. Accurate training of
      emergency staff is necessary to recognise this group of patients to ensure proper
      clinical monitoring and timely treatment.

PMID- 28741584
TI  - Pitfall of modern genetics: recurrent erysipelas masquerading as autoinflammatory
      disease.
AB  - A patient presented with recurrent episodes of fever and skin rash for eight
      years. DNA analysis of the NLRP3 gene revealed a mutation associated with
      autoinflammatory disease. After an initial positive response to the biological
      anakinra, the patient deteriorated. Reassessment revealed recurrent erysipelas.
      In conclusion, sometimes erysipelas-like skin rash is real erysipelas, and DNA
      results are not always the final answer.

PMID- 28741585
TI  - A fatal case of metastatic squamous cell carcinoma in a patient with myositis
      ossificans traumatica.
AB  - Myositis ossificans traumatica is a rare disease associated with chronic wounds
      and fistulae. Chronic ulcers, fistulae and wounds can transform into squamous
      cell carcinoma, the so-called Marjolin's ulcer. We describe a rapid, progressive
      and fulminant course of a metastatic squamous cell carcinoma arising from a
      chronic wound in a patient with myositis ossificans traumatica.

PMID- 28741586
TI  - A new mutation in the calcium-sensing receptor gene causing hypocalcaemia: case
      report of a father and two sons.
AB  - BACKGROUND: Regulation of calcium is mediated by parathyroid hormone (PTH) and
      1.25-dihydroxyvitamine D3. The calcium-sensing receptor (CaSR) regulates PTH
      release by a negative feedback system. Gain-of-function mutations in the CaSR
      gene reset the calcium-PTH axis, leading to hypocalcaemia. PATIENTS AND METHODS:
      We analysed a family with hypocalcaemia. The proband was a 47-year-old man
      (index, patient I1), who presented with paraesthesias in both limbs. He has two
      sons (patient II1 a nd I I2). The probands' lab results showed: serum calcium of
      1.95 mmol/l, albumin 41 g/l, phosphate 0.81 mmol/l and PTH 6.6 ng/l (normal 15-65
      ng/l). Based on this analysis, we suspected a hereditary form of hypocalcaemia
      and performed genetic testing by polymerase chain reaction and Sanger sequencing
      of the coding regions and intron boundaries of the CaSR gene. Genetic analysis
      revealed a new heterozygous mutation: c.2195A>G, p.(Asn732Ser) in exon 7. The lab
      results of patient II1 showed: serum calcium of 1.93 mmol/l, phosphate 1.31
      mmol/l, albumin 41 g/l, and PTH 24.3 ng/l. His genotype revealed the same
      activating mutation and, like his father, he also lost his scalp hair at an early
      adolescent age. Patient II2 is asymptomatic, and has neither biochemical
      abnormalities, nor the familial CaSR gene mutation. He still has all his scalp
      hair. CONCLUSIONS: 1) The c.2195A>G, p.(Asn732Ser) mutation in exon 7 of the CaSR
      gene leads to hypocalcaemia, and has not been reported before in the medical
      literature. 2) Possibly, this mutation is linked to premature baldness.

PMID- 28741588
TI  - Answer to Photo Quiz: A young woman with acute renal failure.

PMID- 28741587
TI  - A young woman with acute renal failure.

PMID- 28741590
TI  - Answer to Photo Quiz: Cutaneous adverse effects of immunotherapy.

PMID- 28741589
TI  - Cutaneous adverse effects of immunotherapy.

PMID- 28741592
TI  - Answer to Photo Quiz: Invalidating painful foot.

PMID- 28741591
TI  - Invalidating painful foot.

PMID- 28741593
TI  - Electro-cutaneous stimulation on the palm elicits referred sensations on intact
      but not on amputated digits.
AB  - OBJECTIVE: Grasping and manipulation control critically depends on tactile
      feedback. Without this feedback, the ability for fine control of a prosthesis is
      limited in upper limb amputees. Early studies have shown that non-invasive
      electro-cutaneous stimulation (ES) can induce referred sensations that are spread
      to a wider and/or more distant area, with respect to the electrodes. Building on
      this, we sought to exploit this effect to provide somatotopically matched sensory
      feedback to people with partial hand (digital) amputations. APPROACH: For the
      first time, this work investigated the possibility of inducing referred
      sensations in the digits by activating the palmar nerves. Specifically, we
      electrically stimulated 18 sites on the palm of non-amputees to evaluate the
      effects of sites and stimulation parameters on modality, magnitude, and location
      of the evoked sensations. We performed similar tests with partial hand amputees
      by testing those sites that had most consistently elicited referred sensations in
      non-amputees. MAIN RESULTS: We demonstrated referred sensations in non-amputees
      from all stimulation sites in one form or another. Specifically, the stimulation
      of 16 of the 18 sites gave rise to reliable referred sensations. Amputees
      experienced referred sensations to unimpaired digits, just like non-amputees, but
      we were unable to evoke referred sensations in their missing digits: none of them
      reported sensations that extended beyond the tip of the stump. SIGNIFICANCE: The
      possibility of eliciting referred sensations on the digits may be exploited in
      haptic systems for providing touch sensations without obstructing the fingertips
      or their movements. The study also suggests that the phenomenon of referred
      sensations through ES may not be exploited for partial hand prostheses, and it
      invites researchers to explore alternative approaches. Finally, the results seem
      to confirm previous studies suggesting that the stumps in partial hand amputees
      partially acquire the role of the missing fingertips, physiologically and
      cognitively.

PMID- 28741594
TI  - Polar phase transitions in heteroepitaxial stabilized La0.5Y0.5AlO3 thin films.
AB  - We report on the fabrication of epitaxial La0.5Y0.5AlO3 ultrathin films on (001)
      LaAlO3 substrates. Structural characterizations by scanning transmission electron
      microscopy and x-ray diffraction confirm the high quality of the film with a - b
      + c - AlO6 octahedral tilt pattern. Unlike either of the nonpolar parent
      compound, LaAlO3 and YAlO3, second harmonic generation measurements on the thin
      films suggest a nonpolar-polar phase transition at T c near 500 K, and a polar
      polar phase transition at T a near 160 K. By fitting the angular dependence of
      the second harmonic intensities, we further propose that the two polar structures
      can be assigned to the Pmc2 1 and Pmn2 1 space group, while the high temperature
      nonpolar structure belongs to the Pbnm space group.

PMID- 28741595
TI  - 3D range-modulator for scanned particle therapy: development, Monte Carlo
      simulations and experimental evaluation.
AB  - The purpose of this work was to design and manufacture a 3D range-modulator for
      scanned particle therapy. The modulator is intended to create a highly conformal
      dose distribution with only one fixed energy, simultaneously reducing
      considerably the treatment time. As a proof of concept, a 3D range-modulator was
      developed for a spherical target volume with a diameter of 5 cm, placed at a
      depth of 25 cm in a water phantom. It consists of a large number of thin pins
      with a well-defined shape and different lengths to modulate the necessary shift
      of the Bragg peak. The 3D range-modulator was manufactured with a rapid
      prototyping technique. The FLUKA Monte Carlo package was used to simulate the
      modulating effect of the 3D range-modulator and the resulting dose distribution.
      For that purpose, a special user routine was implemented to handle its complex
      geometrical contour. Additionally, FLUKA was extended with the capability of
      intensity modulated scanning. To validate the simulation results, dose
      measurements were carried out at the Heidelberg Ion Beam Therapy Center with a
      400.41 MeV/u 12C beam. The high resolution dosimetric measurements show a good
      agreement between simulated and measured dose distributions. Irradiation of the
      monoenergetic raster plan took 3 s, which is approximately 20 times shorter than
      a comparable plan with 16 different energies. The combination of only one energy
      and a 3D range-modulator leads to a tremendous decrease in irradiation time.
      'Interplay effects', typical for moving targets and pencil beam scanning, can be
      immensely reduced or disappear completely, making the delivery of a homogeneous
      dose to moving targets more reliable. Combining high dose conformity, very good
      homogeneity and extremely short irradiation times, the 3D range-modulator is
      considered to become a clinically applicable method for very fast treatment of
      lung tumours.

PMID- 28741596
TI  - The response of MRI contrast parameters in in vitro tissues and tissue mimicking
      phantoms to fractionation by histotripsy.
AB  - Histotripsy is a non-invasive, focused ultrasound lesioning technique that can
      ablate precise volumes of soft tissue using a novel mechanical fractionation
      mechanism. Previous research suggests that magnetic resonance imaging (MRI) may
      be a sensitive image-based feedback mechanism for histotripsy. However, there are
      insufficient data to form some unified understanding of the response of the MR
      contrast mechanisms in tissues to histotripsy. In this paper, we investigate the
      response of the MR contrast parameters R1, R2, and the apparent diffusion
      coefficient (ADC) to various treatment levels of histotripsy in in vitro porcine
      liver, kidney, muscle, and blood clot as well in formulations of bovine red blood
      cells suspended in agar gel. We also make a histological analysis of histotripsy
      lesions in porcine liver. We find that R2 and the ADC are both sensitive to
      ablation in all materials tested here, and the degree of response varies with
      tissue type. Correspondingly, under histologic analysis, the porcine liver
      exhibited various levels of mechanical disruption and necrotic debris that are
      characteristic of histotripsy. While the area of intact red blood cells and
      nuclei found within these lesions both decreased with increasing amounts of
      treatment, the area of red blood cells decreased much more rapidly than the area
      of intact nuclei. Additionally, the decrease in area of intact red blood cells
      saturated at the same treatment levels at which the response of the R2 saturated
      while the area of intact nuclei appeared to vary linearly with the response of
      the ADC.

PMID- 28741597
TI  - Motion compensation for cone-beam CT using Fourier consistency conditions.
AB  - In cone-beam CT, involuntary patient motion and inaccurate or irreproducible
      scanner motion substantially degrades image quality. To avoid artifacts this
      motion needs to be estimated and compensated during image reconstruction. In
      previous work we showed that Fourier consistency conditions (FCC) can be used in
      fan-beam CT to estimate motion in the sinogram domain. This work extends the FCC
      to [Formula: see text] cone-beam CT. We derive an efficient cost function to
      compensate for [Formula: see text] motion using [Formula: see text] detector
      translations. The extended FCC method have been tested with five translational
      motion patterns, using a challenging numerical phantom. We evaluated the root
      mean-square-error and the structural-similarity-index between motion corrected
      and motion-free reconstructions. Additionally, we computed the mean-absolute
      difference (MAD) between the estimated and the ground-truth motion. The practical
      applicability of the method is demonstrated by application to respiratory motion
      estimation in rotational angiography, but also to motion correction for weight
      bearing imaging of knees. Where the latter makes use of a specifically modified
      FCC version which is robust to axial truncation. The results show a great
      reduction of motion artifacts. Accurate estimation results were achieved with a
      maximum MAD value of 708 MUm and 1184 MUm for motion along the vertical and
      horizontal detector direction, respectively. The image quality of reconstructions
      obtained with the proposed method is close to that of motion corrected
      reconstructions based on the ground-truth motion. Simulations using noise-free
      and noisy data demonstrate that FCC are robust to noise. Even high-frequency
      motion was accurately estimated leading to a considerable reduction of streaking
      artifacts. The method is purely image-based and therefore independent of any
      auxiliary data.

PMID- 28741598
TI  - Plasmonic enhancement of cyanine dyes for near-infrared light-triggered
      photodynamic/photothermal therapy and fluorescent imaging.
AB  - Near-infrared (NIR) triggered cyanine dyes have attracted considerable attention
      in multimodal tumor theranostics. However, NIR cyanine dyes used in tumor
      treatment often suffer from low fluorescence intensity and weak singlet oxygen
      generation efficiency, resulting in inadequate diagnostic and therapy efficacy
      for tumors. It is still a great challenge to improve both the photodynamic
      therapy (PDT) and fluorescent imaging (FLI) efficacy of cyanine dyes in tumor
      applications. Herein, a novel multifunctional nanoagent AuNRs@SiO2-IR795 was
      developed to realize the integrated photothermal/photodynamic therapy (PTT/PDT)
      and FLI at a very low dosage of IR795 (0.4 MUM) based on metal-enhanced
      fluorescence (MEF) effects. In our design, both the fluorescence intensity and
      reactive oxygen species of AuNRs@SiO2-IR795 nanocomposites were significantly
      enhanced up to 51.7 and 6.3 folds compared with free IR795, owing to the
      localized surface plasmon resonance band of AuNRs overlapping with the absorption
      or fluorescence emission band of the IR795 dye. Under NIR laser irradiation, the
      cancer cell inhibition efficiency in vitro with synergetic PDT/PTT was up to
      82.3%, compared with 10.3% for free IR795. Moreover, the enhanced fluorescence
      intensity of our designed nanocomposites was helpful to track their behavior in
      tumor cells. Therefore, our designed nanoagents highlight the applications of
      multimodal diagnostics and therapy in tumors based on MEF.

PMID- 28741599
TI  - Dynamics and heat diffusion of Abrikosov's vortex-antivortex pairs during an
      annihilation process.
AB  - The manipulation and control of vortex states in superconducting systems are of
      great interest in view of possible applications, for which mesoscopic materials
      are good candidates. In this work, we studied the annihilation dynamics and the
      dissipative aspects of an Abrikosov's vortex-antivortex pair in a mesoscopic
      superconducting system with a concentric hole. The generalized time-dependent
      Ginzburg-Landau equations were numerically solved. The main result is the
      appearance of a phase slip-like line due to the elongation of the vortex and
      antivortex cores. Under specific circumstances, thermal dissipation might be
      associated with a sizeable relaxation of the order parameter, so that the energy
      released in the annihilation of a vortex-antivortex pair might become detectable
      in measurements of the magnetization as a function of time.

PMID- 28741601
TI  - Obituary-Andre Allisy 1924-2017.

PMID- 28741600
TI  - Coverage-based constraints for IMRT optimization.
AB  - Radiation therapy treatment planning requires an incorporation of uncertainties
      in order to guarantee an adequate irradiation of the tumor volumes. In current
      clinical practice, uncertainties are accounted for implicitly with an expansion
      of the target volume according to generic margin recipes. Alternatively, it is
      possible to account for uncertainties by explicit minimization of objectives that
      describe worst-case treatment scenarios, the expectation value of the treatment
      or the coverage probability of the target volumes during treatment planning. In
      this note we show that approaches relying on objectives to induce a specific
      coverage of the clinical target volumes are inevitably sensitive to variation of
      the relative weighting of the objectives. To address this issue, we introduce
      coverage-based constraints for intensity-modulated radiation therapy (IMRT)
      treatment planning. Our implementation follows the concept of coverage-optimized
      planning that considers explicit error scenarios to calculate and optimize
      patient-specific probabilities [Formula: see text] of covering a specific target
      volume fraction [Formula: see text] with a certain dose [Formula: see text].
      Using a constraint-based reformulation of coverage-based objectives we eliminate
      the trade-off between coverage and competing objectives during treatment
      planning. In-depth convergence tests including 324 treatment plan optimizations
      demonstrate the reliability of coverage-based constraints for varying levels of
      probability, dose and volume. General clinical applicability of coverage-based
      constraints is demonstrated for two cases. A sensitivity analysis regarding
      penalty variations within this planing study based on IMRT treatment planning
      using (1) coverage-based constraints, (2) coverage-based objectives, (3)
      probabilistic optimization, (4) robust optimization and (5) conventional margins
      illustrates the potential benefit of coverage-based constraints that do not
      require tedious adjustment of target volume objectives.

PMID- 28741603
TI  - Role of the Lung Microbiome in the Pathogenesis of Chronic Obstructive Pulmonary
      Disease.
AB  - OBJECTIVE: The development of culture-independent techniques for microbiological
      analysis shows that bronchial tree is not sterile in either healthy or chronic
      obstructive pulmonary disease (COPD) individuals. With the advance of sequencing
      technologies, lung microbiome has become a new frontier for pulmonary disease
      research, and such advance has led to better understanding of the lung microbiome
      in COPD. This review aimed to summarize the recent advances in lung microbiome,
      its relationships with COPD, and the possible mechanisms that microbiome
      contributed to COPD pathogenesis. DATA SOURCES: Literature search was conducted
      using PubMed to collect all available studies concerning lung microbiome in COPD.
      The search terms were "microbiome" and "chronic obstructive pulmonary disease",
      or "microbiome" and "lung/pulmonary". STUDY SELECTION: The papers in English
      about lung microbiome or lung microbiome in COPD were selected, and the type of
      articles was not limited. RESULTS: The lung is a complex microbial ecosystem; the
      microbiome in lung is a collection of viable and nonviable microbiota (bacteria,
      viruses, and fungi) residing in the bronchial tree and parenchymal tissues, which
      is important for health. The following types of respiratory samples are often
      used to detect the lung microbiome: sputum, bronchial aspirate, bronchoalveolar
      lavage, and bronchial mucosa. Disordered bacterial microbiome is participated in
      pathogenesis of COPD; there are also dynamic changes in microbiota during COPD
      exacerbations. Lung microbiome may contribute to the pathogenesis of COPD by
      manipulating inflammatory and/or immune process. CONCLUSIONS: Normal lung
      microbiome could be useful for prophylactic or therapeutic management in COPD,
      and the changes of lung microbiome could also serve as biomarkers for the
      evaluation of COPD.

PMID- 28741604
TI  - Bronchial Washing Cytology of Pulmonary Langerhans Cell Histiocytosis: A Case
      Report.

PMID- 28741605
TI  - A Rare Case of Intramural Mullerian Adenosarcoma Arising from Adenomyosis of the
      Uterus.
AB  - Mullerian adenosarcomas usually arise as polypoid masses in the endometrium of
      post-menopausal women. Occasionally, these tumors arise in the cervix, vagina,
      broad and round ligaments, ovaries and rarely in extragenital sites; these cases
      are generally associated with endometriosis. We experienced a rare case of
      extraendometrial, intramural adenosarcoma arising in a patient with adenomyosis.
      A 40-year-old woman presented with sudden-onset suprapubic pain. The imaging
      findings suggested leiomyoma with cystic degeneration in the uterine fundus. An
      ill-defined ovoid tumor with hemorrhagic degeneration, measuring 7.5 cm in
      diameter, was detected. The microscopic findings showed glandular cells without
      atypia and a sarcomatous component with pleomorphism and high mitotic rates.
      There was no evidence of endometrial origin. To recognize that adenosarcoma can,
      although rarely, arise from adenomyosis is important to avoid overstaging and
      inappropriate treatment.

PMID- 28741606
TI  - Making magic bullets.

PMID- 28741607
TI  - The importance of anabolism in microbial control over soil carbon storage.

PMID- 28741608
TI  - Archaeal evolution: The methanogenic roots of Archaea.

PMID- 28741610
TI  - Stop neglecting fungi.

PMID- 28741609
TI  - Synthetic biology: Engineered stable ecosystems.

PMID- 28741611
TI  - An antimicrobial peptide that inhibits translation by trapping release factors on
      the ribosome.
AB  - Many antibiotics stop bacterial growth by inhibiting different steps of protein
      synthesis. However, no specific inhibitors of translation termination are known.
      Proline-rich antimicrobial peptides, a component of the antibacterial defense
      system of multicellular organisms, interfere with bacterial growth by inhibiting
      translation. Here we show that Api137, a derivative of the insect-produced
      antimicrobial peptide apidaecin, arrests terminating ribosomes using a unique
      mechanism of action. Api137 binds to the Escherichia coli ribosome and traps
      release factor (RF) RF1 or RF2 subsequent to the release of the nascent
      polypeptide chain. A high-resolution cryo-EM structure of the ribosome complexed
      with RF1 and Api137 reveals the molecular interactions that lead to RF trapping.
      Api137-mediated depletion of the cellular pool of free release factors causes the
      majority of ribosomes to stall at stop codons before polypeptide release, thereby
      resulting in a global shutdown of translation termination.

PMID- 28741612
TI  - An information theoretic framework reveals a tunable allosteric network in group
      II chaperonins.
AB  - ATP-dependent allosteric regulation of the ring-shaped group II chaperonins
      remains ill defined, in part because their complex oligomeric topology has
      limited the success of structural techniques in suggesting allosteric
      determinants. Further, their high sequence conservation has hindered the
      prediction of allosteric networks using mathematical covariation approaches.
      Here, we develop an information theoretic strategy that is robust to residue
      conservation and apply it to group II chaperonins. We identify a contiguous
      network of covarying residues that connects all nucleotide-binding pockets within
      each chaperonin ring. An interfacial residue between the networks of neighboring
      subunits controls positive cooperativity by communicating nucleotide occupancy
      within each ring. Strikingly, chaperonin allostery is tunable through single
      mutations at this position. Naturally occurring variants at this position that
      double the extent of positive cooperativity are less prevalent in nature. We
      propose that being less cooperative than attainable allows chaperonins to support
      robust folding over a wider range of metabolic conditions.

PMID- 28741613
TI  - Board Review Vignette: PPP Syndrome: Pancreatitis, Panniculitis, Polyarthritis.

PMID- 28741614
TI  - Diet and Risk of Cholecystectomy: A Prospective Study Based on the French E3N
      Cohort.
AB  - OBJECTIVES: This study aimed to examine the relationship between diet and
      cholecystectomy risk, using three approaches, in a large French cohort. METHODS:
      In a prospective cohort study in French women who completed a food-frequency
      questionnaire at baseline, we analyzed diet with three approaches: food groups,
      dietary patterns obtained by factor analysis, and the Mediterranean diet score.
      The primary outcome was cholecystectomy. We used Cox proportional hazards
      regression to assess the relationship between diet and cholecystectomy risk,
      adjusting for the main potential confounders. RESULTS: During 1,033,955 person
      years of follow-up, we identified 2,778 incident cases of cholecystectomy. Higher
      intakes of legumes, fruit, vegetable oil, and wholemeal bread were associated
      with decreased cholecystectomy risk. Two dietary patterns were identified by
      factor analysis: "Western" (essentially processed meat, pizza, pies, high-alcohol
      beverages, French fries, sandwiches...) and "Mediterranean" (essentially fruits,
      vegetables, seafood, and olive oil). The "Mediterranean" pattern was inversely
      associated with cholecystectomy risk in the subgroup of postmenopausal women who
      ever used menopausal hormone therapy (hazard ratio for quartile 4 vs. 1=0.79, 95%
      confidence interval (CI): 0.65-0.95; P for linear trend=0.008). High adherence to
      the Mediterranean diet was associated with decreased risk of cholecystectomy
      (hazard ratio for a 6-9 score vs. 0-3=0.89, 95% CI: 0.80-0.99; P for linear
      trend=0.02). CONCLUSIONS: Adherence to a diet rich in fruit, vegetables, legumes,
      and olive oil was associated with a reduction in cholecystectomy risk in French
      women. Further studies in different settings are requested.

PMID- 28741615
TI  - Patient and Disease Characteristics Associated With the Presence of Diabetes
      Mellitus in Adults With Chronic Pancreatitis in the United States.
AB  - OBJECTIVES: Diabetes mellitus (DM) is a common complication of chronic
      pancreatitis (CP). Past studies for DM risk factors in CP have been limited to
      single centers or highly focused on a single etiology such as alcoholic or
      hereditary disease. We studied risk factors for DM in a large population of
      patients with CP of all etiologies enrolled in the North American Pancreatitis 2
      studies. METHODS: Participants (1,171) with CP (n=383 with DM, n=788 without DM)
      were enrolled prospectively from 26 participating centers. Questionnaires were
      completed by patients and physicians in a cross-sectional assessment. Patient
      demographics and disease characteristics were compared for CP with DM vs. without
      DM. Logistic regression was performed to assess the variables associated with DM
      diagnosis in a multivariable model. RESULTS: Diabetics were more likely to be
      black (P=0.02), overweight, or obese (P<0.001), and with a family history of DM
      (P=0.0005). CP patients with DM were more likely to have pancreatic
      calcifications (63% vs. 54%, P=0.002), atrophy (44% vs. 32%, P<0.0001), and prior
      pancreas surgery (26.9% vs. 16.9%, P<0.0001). In multivariate logistic regression
      modeling, the strongest risk factors for DM were obesity (odds ratio (OR) 2.8,
      95% confidence interval (CI) 1.9, 4.2) and exocrine insufficiency (OR 2.4, 95% CI
      1.8, 3.2). CONCLUSIONS: In this large multicenter cohort of patients with CP,
      exocrine insufficiency, calcifications, and pancreas surgery conveyed higher odds
      of having DM. However, the traditional 'type 2 DM' risk factors of obesity and
      family history were similarly important in conveying risk for DM.

PMID- 28741616
TI  - Rural and Urban Residence During Early Life is Associated with Risk of
      Inflammatory Bowel Disease: A Population-Based Inception and Birth Cohort Study
AB  - OBJECTIVES: To determine the association between inflammatory bowel disease (IBD)
      and rural/urban household at the time of diagnosis, or within the first 5 years
      (y) of life. METHODS: Population-based cohorts of residents of four Canadian
      provinces were created using health administrative data. Rural/urban status was
      derived from postal codes based on population density and distance to
      metropolitan areas. Validated algorithms identified all incident IBD cases from
      administrative data (Alberta: 1999-2008, Manitoba and Ontario: 1999-2010, and
      Nova Scotia: 2000-2008). We determined sex-standardized incidence (per 100,000
      patient-years) and incident rate ratios (IRR) using Poisson regression. A birth
      cohort was created of children in whom full administrative data were available
      from birth (Alberta 1996-2010, Manitoba 1988-2010, and Ontario 1991-2010). IRR
      was calculated for residents who lived continuously in rural/urban households
      during each of the first 5 years of life. RESULTS: There were 6,662 rural
      residents and 38,905 urban residents with IBD. Incidence of IBD per 100,000 was
      33.16 (95% CI 27.24-39.08) in urban residents, and 30.72 (95% CI 23.81-37.64) in
      rural residents (IRR 0.90, 95% CI 0.81-0.99). The protective association was
      strongest in children <10 years (IRR 0.58, 95% CI 0.43-0.73) and 10-17.9 years
      (IRR 0.72, 95% CI 0.64-0.81). In the birth cohort, comprising 331 rural and 2,302
      urban residents, rurality in the first 1-5 years of life was associated with
      lower risk of IBD (IRR 0.75-0.78). CONCLUSIONS: People living in rural households
      had lower risk of developing IBD. This association is strongest in young children
      and adolescents, and in children exposed to the rural environment early in life.

PMID- 28741617
TI  - Gastrointestinal cancer: Establishing a family tree.

PMID- 28741619
TI  - Pancreatic Cancer: EGFR inhibition is effective against KRAS-wild-type disease.

PMID- 28741620
TI  - Altered neurogenesis and disrupted expression of synaptic proteins in prefrontal
      cortex of SHANK3-deficient non-human primate.

PMID- 28741621
TI  - Fetal dendritic cells give mum a break.

PMID- 28741618
TI  - The immune contexture in cancer prognosis and treatment.
AB  - Immunotherapy is currently the most rapidly advancing area of clinical oncology,
      and provides the unprecedented opportunity to effectively treat, and even cure,
      several previously untreatable malignancies. A growing awareness exists of the
      fact that the success of chemotherapy and radiotherapy, in which the patient's
      disease can be stabilized well beyond discontinuation of treatment (and
      occasionally is cured), also relies on the induction of a durable anticancer
      immune response. Indeed, the local immune infiltrate undergoes dynamic changes
      that accompany a shift from a pre-existing immune response to a therapy-induced
      immune response. As a result, the immune contexture, which is determined by the
      density, composition, functional state and organization of the leukocyte
      infiltrate of the tumour, can yield information that is relevant to prognosis,
      prediction of a treatment response and various other pharmacodynamic parameters.
      Several complementary technologies can be used to explore the immune contexture
      of tumours, and to derive biomarkers that could enable the adaptation of
      individual treatment approaches for each patient, as well as monitoring a
      response to anticancer therapies.

PMID- 28741622
TI  - In Vivo Detection of CPP-115 Target Engagement in Human Brain.
AB  - CPP-115, a next-generation gamma-amino butyric acid (GABA)-aminotransferase (AT)
      inhibitor, shows comparable pharmacokinetics, improved safety and tolerability,
      and a more favorable toxicity profile when compared with vigabatrin. The
      pharmacodynamic characteristics of CPP-115 remain to be evaluated. The present
      study employed state-of-the-art proton magnetic resonance spectroscopy techniques
      to measure changes in brain GABA+ (the composite resonance of GABA,
      homocarnosine, and macromolecules) concentrations in healthy subjects receiving
      oral daily doses of CPP-115 or placebo. Six healthy adult males were randomized
      to receive either single daily 80 mg doses of CPP-115 (n=4) or placebo (n=2) for
      6, 10, or 14 days. Metabolite-edited spectra and two-dimensional J-resolved
      spectroscopy data were acquired from the parietal-occipital cortex and
      supplementary motor area in all subjects. Four scans were performed in each
      subject that included a predrug baseline measure, two scans during the dosing
      timeframe, and a final scan that occurred 1 week after drug cessation. CPP-115
      induced robust and significant increases in brain GABA+ concentrations that
      ranged between 52 and 141% higher than baseline values. Elevated GABA+
      concentrations returned to baseline values following drug clearance. Subjects
      receiving placebo showed no significant changes in GABA+ concentration. CPP-115
      induced changes were exclusive to GABA and homocarnosine, and CPP-115 afforded
      brain GABA+ concentration changes comparable to or greater than previous
      vigabatrin spectroscopy studies in healthy epilepsy-naive subjects. The return to
      baseline GABA+ concentration indicates the reversible GABA-AT resynthesis
      following drug washout. These preliminary data warrant further spectroscopy
      studies that characterize the acute pharmacodynamic effects of CPP-115 with
      additional dose-descending measures.

PMID- 28741623
TI  - Effects of Suvorexant, a Dual Orexin/Hypocretin Receptor Antagonist, on Impulsive
      Behavior Associated with Cocaine.
AB  - Hypothalamic hypocretin (orexin) peptides mediate arousal, attention, and reward
      processing. Fibers containing orexins project to brain structures that govern
      motivated behavior, including the ventral tegmental area (VTA). A number of
      psychiatric conditions, including attention deficit hyperactivity disorder (ADHD)
      and substance use disorders, are characterized by deficits in impulse control,
      however the relationship between orexin and impulsive behavior is incompletely
      characterized. The effects of systemic or centrally administered orexin receptor
      (OXR) antagonists on measures of impulsive-like behavior in rats were evaluated
      using the five-choice serial reaction time task (5-CSRTT) and delay discounting
      procedures. These paradigms were also used to test the capacity of OXR
      antagonists to attenuate acute cocaine-evoked impulsivity. Finally,
      immunohistochemistry and calcium imaging were used to assess potential cellular
      mechanisms by which OXR blockade may influence motor impulsivity. Suvorexant, a
      dual (OX1/2R) orexin receptor antagonist, reduced cocaine-evoked premature
      responses in 5-CSRTT when administered systemically or directly into VTA. Neither
      suvorexant nor OX1R- or OX2R-selective compounds (SB334867 or TCS-OX2-29,
      respectively) altered delay discounting. Finally, suvorexant did not alter Fos
      immunoreactivity within tyrosine hydroxylase-immunolabeled neurons of VTA, but
      did attenuate cocaine- and orexin-induced increases in calcium transient
      amplitude within neurons of VTA. Results from the present studies suggest
      potential therapeutic utility of OXR antagonists in reducing psychostimulant
      induced motor impulsivity. These findings also support the view that orexin
      transmission is closely involved in executive function in normal and pathological
      conditions.

PMID- 28741624
TI  - Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State
      Networks in Women with Previous Affective Side Effects on the Pill.
AB  - The mechanisms linking ovarian hormones to negative affect are poorly
      characterized, but important clues may come from the examination of the brain's
      intrinsic organization. Here, we studied the effects of both the menstrual cycle
      and oral contraceptives (OCs) on amygdala and salience network resting-state
      functional connectivity using a double-blind, randomized, and placebo-controlled
      design. Hormone levels, depressive symptoms, and resting-state functional
      connectivity were measured in 35 healthy women (24.9+/-4.2 years) who had
      previously experienced OC-related negative affect. All participants were examined
      in the follicular phase of a baseline cycle and in the third week of the
      subsequent cycle during treatment with either a combined OC (30 MUg ethinyl
      estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the
      midluteal phase in placebo users and steady-state ethinyl estradiol and
      levonorgestrel concentrations in OC users. Amygdala and salience network
      connectivity generally increased with both higher endogenous and synthetic
      hormone levels, although amygdala-parietal cortical connectivity decreased in OC
      users. When in the luteal phase, the naturally cycling placebo users demonstrated
      higher connectivity in both networks compared with the women receiving OCs. Our
      results support a causal link between the exogenous administration of synthetic
      hormones and amygdala and salience network connectivity. Furthermore, they
      suggest a similar, potentially stronger, association between the natural hormonal
      variations across the menstrual cycle and intrinsic network connectivity.

PMID- 28741625
TI  - Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit
      Hyperactivity Disorder: a Systematic Review and Meta-Analysis of Clinical Trials
      and Biological Studies.
AB  - The role of omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) in the
      pathogenesis and treatment of children and adolescents with attention deficit
      hyperactivity disorder (ADHD) is unclear. A systematic review followed by meta
      analysis was conducted on: (1) randomized controlled trials (RCTs) assessing the
      effects of n-3 PUFAs on clinical symptoms and cognition in children and
      adolescent with ADHD; and (2) case-control studies assessing the levels of n-3
      PUFAs in blood and buccal tissues of children and adolescents with ADHD. In seven
      RCTs, totalling n=534 randomized youth with ADHD, n-3 PUFAs supplementation
      improves ADHD clinical symptom scores (g=0.38, p<0.0001); and in three RCTs,
      totalling n=214 randomized youth with ADHD, n-3 PUFAs supplementation improves
      cognitive measures associated with attention (g=1.09, p=0.001). Moreover,
      children and adolescents with ADHD have lower levels of DHA (seven studies,
      n=412, g=-0.76, p=0.0002), EPA (seven studies, n=468, g=-0.38, p=0.0008), and
      total n-3 PUFAs (six studies, n=396, g=-0.58, p=0.0001). In summary, there is
      evidence that n-3 PUFAs supplementation monotherapy improves clinical symptoms
      and cognitive performances in children and adolescents with ADHD, and that these
      youth have a deficiency in n-3 PUFAs levels. Our findings provide further support
      to the rationale for using n-3 PUFAs as a treatment option for ADHD.

PMID- 28741626
TI  - Dopamine and Stress System Modulation of Sex Differences in Decision Making.
AB  - Maladaptive decision making is associated with several neuropsychiatric
      disorders, including problem gambling and suicidal behavior. The prevalence of
      these disorders is higher in men vs women, suggesting gender-dependent regulation
      of their pathophysiology underpinnings. We assessed sex differences in decision
      making using the rat version of the Iowa gambling task. Female rats identified
      the most optimal choice from session 1, whereas male rats from session 5. Male,
      but not female rats, progressively improved their advantageous option responding
      and surpassed females. Estrus cycle phase did not affect decision making. To test
      whether pharmacological manipulations targeting the dopaminergic and stress
      systems affect decision making in a sex-dependent manner, male and female rats
      received injections of a dopamine D2 receptor (D2R) antagonist (eticlopride), D2R
      agonist (quinpirole), corticotropin-releasing factor 1 (CRF1) antagonist
      (antalarmin), and alpha2-adrenergic receptor antagonist (yohimbine; used as a
      pharmacological stressor). Alterations in mRNA levels of D2R and CRF1 were also
      assessed. Eticlopride decreased advantageous responding in male, but not female
      rats, whereas quinpirole decreased advantageous responding specifically in
      females. Yohimbine dose-dependently decreased advantageous responding in female
      rats, whereas decreased advantageous responding was only observed at higher doses
      in males. Antalarmin increased optimal choice responding only in female rats.
      Higher Drd2 and Crhr1 expression in the amygdala were observed in female vs male
      rats. Higher amygdalar Crhr1 expression was negatively correlated with
      advantageous responding specifically in females. This study demonstrates the
      relevance of dopaminergic- and stress-dependent sex differences to maladaptive
      decision making.

PMID- 28741627
TI  - Chronic Exposure to Methamphetamine Disrupts Reinforcement-Based Decision Making
      in Rats.
AB  - The persistent use of psychostimulant drugs, despite the detrimental outcomes
      associated with continued drug use, may be because of disruptions in
      reinforcement-learning processes that enable behavior to remain flexible and goal
      directed in dynamic environments. To identify the reinforcement-learning
      processes that are affected by chronic exposure to the psychostimulant
      methamphetamine (MA), the current study sought to use computational and
      biochemical analyses to characterize decision-making processes, assessed by
      probabilistic reversal learning, in rats before and after they were exposed to an
      escalating dose regimen of MA (or saline control). The ability of rats to use
      flexible and adaptive decision-making strategies following changes in stimulus
      reward contingencies was significantly impaired following exposure to MA.
      Computational analyses of parameters that track choice and outcome behavior
      indicated that exposure to MA significantly impaired the ability of rats to use
      negative outcomes effectively. These MA-induced changes in decision making were
      similar to those observed in rats following administration of a dopamine D2/3
      receptor antagonist. These data use computational models to provide insight into
      drug-induced maladaptive decision making that may ultimately identify novel
      targets for the treatment of psychostimulant addiction. We suggest that the
      disruption in utilization of negative outcomes to adaptively guide dynamic
      decision making is a new behavioral mechanism by which MA rigidly biases choice
      behavior.

PMID- 28741628
TI  - Prostate cancer: Subtype linked to germline variant.

PMID- 28741630
TI  - Surface chemistry and interface science.

PMID- 28741629
TI  - Low-intensity shockwave therapy for erectile dysfunction: is the evidence strong
      enough?
AB  - Erectile dysfunction (ED) affects ~30% of all men above the age of 40 years and
      its prevalence steadily increases with age. Current nonsurgical treatment
      options, including phosphodiesterase type 5 inhibitors (PDE5I), provide temporary
      relief but have failed to provide a permanent improvement of the condition. Low
      intensity extracorporeal shockwave therapy (Li-ESWT) is noninvasive and uses
      acoustic waves, which can pass through tissue and be focussed to target specific
      areas or organs to induce the desired effects. The use of Li-ESWT has previously
      been described in other disease contexts, such as ischaemic heart disease, bone
      fractures, and burns, in which it improves neoangiogenesis; similar principles
      seem to apply in the erectile tissue. The major potential advantage of the
      treatment, therefore, is the possibility to restore natural erectile function.
      Thus, Li-ESWT is the only currently marketed treatment for ED that might offer a
      cure, which is the most desired outcome for most men with ED. Li-ESWT has also
      been suggested to improve the effect of PDE5I in nonresponders, reducing the need
      for more invasive treatments. Several single-arm trials have shown benefit of Li
      ESWT on patient-reported erectile function scores, but data from randomized
      trials are conflicting, and many questions remain to be answered before we can
      routinely offer this treatment to patients. Thus, the search for the true
      clinical value of Li-ESWT for ED represents a dynamic and continuing field of
      enquiry.

PMID- 28741632
TI  - Strain-induced Stranski-Krastanov growth of Pd@Pt core-shell hexapods and
      octapods as electrocatalysts for methanol oxidation.
AB  - Bimetallic nanocrystals with a branched shape have received great interest as
      catalysts due to their unique structures and fascinating properties. However, the
      conventional synthetic approaches based on the island growth mode often lead to
      the dendritic nanostructures with inhomogeneous and uncontrolled branches. Here
      precise control over the number of branches has been realized in the deposition
      of Pt on Pd seeds through the Stranski-Krastanov growth mechanism. Based on such
      a growth mode, Pd@Pt core-shell hexapods and octapods have been generated by a
      seeded growth with Pd octahedra and cubes as the seeds, respectively. We found
      that Pt atoms are initially deposited on the side faces of Pd seeds through a
      layer-by-layer epitaxial growth in the presence of oleylamine (OAm), leading to a
      local strain focused at their corners. These strain-concentrated sites promote
      the subsequent island growth of Pt atoms at the corners of the Pd seeds,
      resulting in the Pd@Pt core-shell hexapods or octapods. Both the Pd@Pt core-shell
      hexapods and octapods exhibit the substantially enhanced catalytic properties in
      terms of activity and stability towards a methanol oxidation reaction (MOR)
      relative to the commercial Pt/C. Specifically, the Pd@Pt core-shell hexapods show
      the highest specific (1.97 mA cm-2) activity and mass activity (0.52 mA MUgPt-1)
      for the MOR, which are 5.8 and 2.6 times higher than those of the commercial
      Pt/C, respectively. This enhancement can probably be attributed to their unique
      structures and the synergistic effect between Pt and Pd.

PMID- 28741634
TI  - Mitochondria-targeting near-infrared light-triggered thermosensitive liposomes
      for localized photothermal and photodynamic ablation of tumors combined with
      chemotherapy.
AB  - Lonidamine, an anticancer drug that acts on mitochondria, has poor water
      solubility. Mitochondria are the primary source of cellular reactive oxygen
      species (ROS), which are necessary for photodynamic therapy. Hence, a
      mitochondria-targeting drug delivery system loaded with Lonidamine and a ROS
      produced photosensitizer could improve the bioavailability of Lonidamine and
      maximize photodynamic therapeutic efficiency. Here we report, for the first time,
      new IR-780 and Lonidamine encapsulated mitochondria-targeting thermosensitive
      liposomes (IL-TTSL). DSPE-PEG2000-NH2 was coupled with triphenylphosphine to form
      DSPE-PEG2K-TPP. The liposomes (IL-TTSL) were self-assembled from DPPC, DSPC, DSPE
      PEG2K-TPP, cholesterol, IR-780 and Lonidamine. Coupled linker modified
      triphenylphosphine (TPP) is cationic and can selectively accumulate several
      hundred-fold within mitochondria. Once the liposomes are located inside
      mitochondria, 808 nm laser irradiation could trigger photosensitizer IR-780 to
      elevate the local temperature, which could be utilized in photothermal therapy
      and induce the release of Lonidamine from the thermosensitive liposomes.
      Meanwhile, IR-780 could release ROS for photodynamic therapy in mitochondria and
      increase photodynamic therapeutic efficiency. Our results showed that the surface
      modification of the liposomes with triphenylphosphine cations had good
      mitochondria-targeting ability. The liposomes exhibited good biocompatibility and
      all components of the empty liposomes were safe to be used in humans. Few reports
      were related to IR-780 being used in photodynamic therapy and we proved this
      function of IR-780. Overall, the stealth liposomes provide a promising new
      strategy to realize mitochondria-targeting thermosensitive chemo-, photodynamic
      and photothermal combination therapy with a single light source for lung cancer.

PMID- 28741635
TI  - Liposomes loading sodium chloride as effective thermo-seeds for microwave
      ablation of hepatocellular carcinoma.
AB  - : Microwave ablation (MWA) is a promising minimally invasive therapy that has
      been widely used to treat hepatocellular carcinoma (HCC). However, the efficiency
      of MWA in treating HCC is evidently limited by the incomplete ablation of large
      tumors and tumors in high-risk locations. Here, we report the value of using
      liposomes packed with sodium chloride (NaCl-LPs) as effective thermo-seeds for
      MWA of HCC. The prepared liposomes exhibited excellent heat conversion ability by
      showing a more rapid temperature increase than free NaCl medium, blank liposomes
      or water under microwave irradiation. The high efficiency of this new microwave
      sensitization strategy was fully demonstrated in vitro in subcutaneous and
      orthotopic tumors. The results showed that MWA combined with NaCl-LPs clearly
      enhanced the ablation efficiency, leading to apparent tumor inhibition and low
      recurrence. What's more, we verified the susceptibility of NaCl-LPs on orthotopic
      tumors. Based on the unique properties of NaCl-LPs, sublethal MWA was used to
      mimic the transitional zone, and large-scale necrosis was observed in tumors
      combined with NaCl-LPs. In addition, HE staining and blood hematology analysis
      revealed no noticeable toxicity of NaCl-LPs in vivo, which confirmed that NaCl
      LPs possessed good biocompatibility. CONCLUSION: The effective nanoparticles
      could play a valuable role in enhancing the thermo-sensitizing effect of MWA for
      achieving better therapeutic efficacy.

PMID- 28741638
TI  - 19F CEST imaging probes for metal ion detection.
AB  - For detecting metal ions with 19F chemical exchange saturation transfer magnetic
      resonance imaging (19F CEST MRI), a class of novel fluorinated chelators with
      diverse fluorine contents and chelation properties were conveniently synthesized
      on gram scales. Among them, a DTPA-derived chelator with high sensitivity and
      selectivity was identified as a novel 19F CEST imaging probe for simultaneously
      detecting multiple metal ions.

PMID- 28741639
TI  - Correction: In vivo evaluation of photodynamic inactivation using
      Photodithazine(r) against Candida albicans.
AB  - Correction for 'In vivo evaluation of photodynamic inactivation using
      Photodithazine(r) against Candida albicans' by J. C. Carmello, et al., Photochem.
      Photobiol. Sci., 2015, 14, 1319-1328.

PMID- 28741641
TI  - Highly oriented Langmuir-Blodgett film of silver cuboctahedra as an effective
      matrix-free sample plate for surface-assisted laser desorption/ionization mass
      spectrometry.
AB  - The design of a homogeneous sample plate to solve the sweet heating spot issues
      is the key step to expand the applicability of surface-assisted laser
      desorption/ionization mass spectrometry (SALDI MS). Herein, large-scale and
      highly oriented Langmuir-Blodgett (LB) films of uniform silver nanocrystals have
      been fabricated as a highly efficient and matrix-free sample plate for SALDI MS.
      Three individual silver nanocrystals (cubes, cuboctahedra and octahedra)
      assembled LB films have been applied as the sample plates for glucose detection
      by SALDI MS without an additional matrix. The results show that the signal
      intensity, background noise, signal-to-noise ratio and reproducibility have been
      significantly improved using LB films as the sample plate in comparison with
      commercial matrixes of CHCA and DHB. In particular, a relative signal of 5.7% was
      obtained for LB films of silver cuboctahedra. The significant improvement in the
      SALDI MS measurement could be attributed to the homogenous dissipation of laser
      irradiation energy to create a large area of the sweet heating spot on well
      oriented silver cuboctahedra-based LB film. This ready-to-use sample plate has
      the potential for widespread commercial applications in SALDI MS.

PMID- 28741642
TI  - Fabricating chiroptical starfruit-like Au nanoparticles via interface modulation
      of chiral thiols.
AB  - The surface/interface matters as the size of materials enters the nanoscale.
      Control of surface/interface, therefore, plays an important role in creating
      novel nanostructures with unusual properties and in obtaining devices with high
      performance. Herein, we demonstrate unique interface regulation in fabricating
      nanostructures with strong plasmonic circular dichroism (PCD). With chiral
      cysteine (Cys) as surface-modulating molecules, starfruit-like Au nanoparticles
      (NPs) with high PCD responses are obtained via Au overgrowth on Au nanorods
      (AuNRs). Pre-incubation of the AuNRs with Cys is vital in achieving strong and
      reproducible PCD responses. Instead of contributing to PCD signals, the pre
      adsorbed Cys molecules are found to play a major role in manipulating the Au
      growth mode and thus the formation of hotspots within the shell. Strong PCD
      signal mainly comes from the entrapped Cys molecules within the hotspots and is
      enhanced via local field effect. The distinct roles of the same ligands at
      different surfaces/interfaces are elucidated. Furthermore, our findings
      contribute to the strategy of utilizing interface modulation to fabricate complex
      nanostructures with novel properties.

PMID- 28741643
TI  - Self-reference plasmonic sensors based on double Fano resonances.
AB  - High-sensitivity plasmonic refractive index sensors show great applications in
      the areas of biomedical diagnostics, healthcare, food safety, environmental
      monitoring, homeland security, and chemical reactions. However, the unstable and
      complicated environments considerably limit their practical applications. By
      employing the independent double Fano resonances in a simple metallic grating, we
      experimentally demonstrate a self-reference plasmonic sensor, which significantly
      reduces the error contributions of the light intensity fluctuations in the long
      distance propagation and local temperature variations at the metallic grating,
      and the detection accuracy is guaranteed. The numerical simulation shows that the
      two Fano resonances have different origins and are independent of each other. As
      a result, the left Fano resonance is quite sensitive to the refractive index
      variations above the metal surface, while the right Fano resonance is insensitive
      to that. Experimentally, a high figure of merit (FOM) of 31 RIU-1 and a FOM* of
      860 RIU-1 are realized by using the left Fano resonance. More importantly, by
      using the right Fano resonance as a reference signal, the influence of the light
      intensity fluctuations and local temperature variations is monitored and
      eliminated in the experiment. This simple self-reference plasmonic sensor based
      on the double Fano resonances may find important applications in highly-sensitive
      and accurate sensing under unstable and complicated environments, as well as
      multi-parameter sensing.

PMID- 28741644
TI  - Highly stereoselective construction of the C2 stereocentre of alpha-tocopherol
      (vitamin E) by asymmetric addition of Grignard reagents to ketones.
AB  - Tertiary alcohol precursors of both C2 diastereoisomers of alpha-tocopherol were
      prepared in three ways by our recently reported asymmetric Grignard synthesis.
      The versatility of Grignard chemistry inherent in its three-way disconnection was
      exploited to allow the synthesis of three product grades: 77 : 23 dr (5 steps),
      81 : 19 dr (5 steps) and 96 : 4 dr (7 steps, one gram scale) from readily
      available and abundant starting materials. The products were converted to their
      respective alpha-tocopherols in 3 steps, which allowed a definitive re-assignment
      of their absolute configurations.

PMID- 28741645
TI  - Inflammasome and autophagy regulation - a two-way street.
AB  - Inflammation plays a significant role in protecting hosts against pathogens.
      Inflammation induced by non-infectious, endogenous agents can be detrimental, and
      if excessive can result in organ and tissue damage. The inflammasome is a major
      innate immune pathway that can be activated via both exogenous pathogen
      associated molecular patterns (PAMPs) and endogenous damage-associated molecular
      patterns (DAMPs). Inflammasome activation involves formation and oligomerization
      of a protein complex including a NOD-like receptor (NLR), an adaptor protein
      (ASC) and procaspase-1. This then allows cleavage and activation of caspase-1,
      followed by downstream cleavage and release of proinflammatory cytokines, IL
      1beta and IL-18, from innate immune cells. Hyperinflammation caused by
      unrestrained inflammasome activation is linked with multiple inflammatory
      diseases, including inflammatory bowel disease, Alzheimer's disease and multiple
      sclerosis. So there is an understandable rush to understand mechanisms that
      regulate such potent inflammatory pathways. Autophagy has now been identified as
      a main regulator of inflammasomes. Autophagy is a vital intracellular process
      involved in cellular homeostasis, recycling and removal of damaged organelles
      (e.g. mitochondria) and intracellular pathogens. Autophagy is regulated by
      proteins that are important in endosomal/phagosomal pathways, as well as by
      specific autophagy proteins coded for by autophagy-related genes. Cytosolic
      components are surrounded and contained by a double-membraned vesicle, which then
      fuses with lysosomes to enable degradation of the contents. Autophagic removal of
      intracellular DAMPs, inflammasome components or cytokines can reduce inflammasome
      activation. Similarly, inflammasomes can regulate the autophagic process,
      allowing for a two-way, mutual regulation of inflammation that may hold the key
      for treatment of multiple diseases.

PMID- 28741646
TI  - Aggressiveness in depression: a neglected symptom possibly associated with
      bipolarity and mixed features.
AB  - OBJECTIVE: To evaluate aggressiveness during a major depressive episode (MDE) and
      its relationship with bipolar disorder (BD) in a post hoc analysis of the BRIDGE
      II-MIX study. METHOD: A total of 2811 individuals were enrolled in this
      multicenter cross-sectional study. MDE patients with (MDE-A, n = 399) and without
      aggressiveness (MDE-N, n = 2412) were compared through chi-square test or
      Student's t-test. A stepwise backward logistic regression model was performed.
      RESULTS: MDE-A group was more frequently associated with BD (P < 0.001), while
      aggressiveness was negatively correlated with unipolar depression (P < 0.001). At
      the logistic regression, aggressiveness was associated with the age at first
      depressive episode (P < 0.001); the severity of mania (P = 0.03); the diagnosis
      of BD (P = 0.001); comorbid borderline personality disorder (BPD) (P < 0.001) but
      not substance abuse (P = 0.63); no current psychiatric treatment (P < 0.001);
      psychotic symptoms (P = 0.007); the marked social/occupational impairment (P =
      0.002). The variable most significantly associated with aggressiveness was the
      presence of DSM-5 mixed features (P < 0.001, OR = 3.815). After the exclusion of
      BPD, the variable of lifetime suicide attempts became significant (P = 0.013, OR
      = 1.405). CONCLUSION: Aggressiveness seems to be significantly associated with
      bipolar spectrum disorders, independently from BPD and substance abuse.
      Aggressiveness should be considered as a diagnostic criterion for the mixed
      features specifier and a target of tailored treatment strategy.

PMID- 28741647
TI  - The association between season of birth, age at onset, and clozapine use in
      schizophrenia.
AB  - OBJECTIVE: This study aimed to determine whether the rate of clozapine use, an
      indicator of refractoriness in schizophrenia, is associated with the season of
      birth and age at onset in patients with schizophrenia based on nationwide data.
      METHODS: Patients with schizophrenia (n = 114 749) who received prescriptions for
      antipsychotic medication between 2008 and 2014 were retrospectively identified
      from the Korean National Health Insurance Service database. The study population
      was divided into three groups based on their age at the onset of schizophrenia
      (early, middle, and late onset). We assessed differences in the month of birth
      between patients and the general population. In addition, the cumulative
      clozapine use was calculated. RESULTS: Compared to the late-onset schizophrenia
      group, the early- and middle-onset groups showed a higher probability of birth
      during the winter season. In addition, the early-onset group showed the highest
      cumulative clozapine use rate. In the middle-onset group, the initiation of
      clozapine use was significantly earlier for patients born in winter compared to
      those born in summer. CONCLUSION: Our results indicate that the age at onset is
      an important factor in predicting the prognosis of schizophrenia patients. The
      season of birth also affects the prognosis, but with less robustness.
      Specifically, it appears that early disease onset and winter birth might be
      associated with poor outcomes in Korean patients with schizophrenia.

PMID- 28741649
TI  - The effect of metrics-based feedback on acquisition of sonographic skills
      relevant to performance of ultrasound-guided axillary brachial plexus block.
AB  - The objective of this study was to examine the effect of metrics-based vs. non
      metrics-based feedback on novices learning predefined competencies for
      acquisition and interpretation of sonographic images relevant to performance of
      ultrasound-guided axillary brachial plexus block. Twelve anaesthetic trainees
      were randomly assigned to either metrics-based-feedback or non-metrics-based
      feedback groups. After a common learning phase, all participants attempted to
      perform a predefined task that involved scanning the left axilla of a single
      volunteer. Following completion of the task, all participants in each group
      received feedback from a different expert in regional blocks (consultant
      anaesthetist) and were allowed to practise the predefined task for up to 1 h.
      Those in the metrics-based feedback group received feedback based on previously
      validated metrics, and they practised each metric item until it was performed
      satisfactorily, as assessed by the supervising consultant. Subsequently, each
      participant attempted to perform ultrasonography of the left axilla on the same
      volunteer. Two trained consultant anaesthetists independently scored the video
      recording pre- and post-feedback scans using the validated metrics list. Both
      groups showed improvement from pre-feedback to post-feedback scores. Compared
      with participants in the non-metrics-based feedback group, those in the metrics
      based feedback group completed more steps: median (IQR [range]) 18.8 (1.5 [17
      20]) vs. 14.3 (4.5 [11-18.5]), p = 0.009, and made fewer errors 0.5 (1 [0-1.5])
      vs. 1.5 (2 [1-6]), p = 0.041 postfeedback. In this study, novices' sonographic
      skills showed greater improvement when feedback was combined with validated
      metrics.

PMID- 28741648
TI  - American cutaneous leishmaniasis in infancy and childhood.
AB  - Infant and young child skin diseases are among the most common features of
      morbidity throughout the tropics. Because the skin is directly exposed to the
      environment, it is considerably affected by climatic and local conditions such as
      vectors and microorganisms, as in the case of leishmaniasis. In America the
      observed magnitude of cutaneous leishmaniasis in children has led to the study of
      increased risk of exposure of this group due to the possibility of peri- and
      intradomiciliary transmission. The present review pretends to make a concrete
      approach all through the broad and main figures of this parasitic disease,
      including the clinical, physiopathological, epidemiological, diagnostic, and
      therapeutic aspects, in order to be used as a practical source of reference for
      pediatricians leading with tropical cutaneous pathology in the region.

PMID- 28741650
TI  - Violence and Vigilance: The Acute Effects of Community Violent Crime on Sleep and
      Cortisol.
AB  - The data combine objectively measured sleep and thrice-daily salivary cortisol
      collected from a 4-day diary study in a large Midwestern city with location data
      on all violent crimes recorded during the same time period for N = 82 children
      (Mage  = 14.90, range = 11.27-18.11). The primary empirical strategy uses a
      within-person design to measure the change in sleep and cortisol from the
      person's typical pattern on the night/day immediately following a local violent
      crime. On the night following a violent crime, children have later bedtimes.
      Children also have disrupted cortisol patterns the following morning.
      Supplementary analyses using varying distances of the crime to the child's home
      address confirm more proximate crimes correspond to later bedtimes.

PMID- 28741651
TI  - Teaching & Learning Tips 5: Making lectures more "active".
AB  - Challenge: Although lecturing is an efficient method for the dissemination of
      information, it has long been criticized for learner passivity and diminished
      knowledge retention. Active learning strategies to engage the audience in the
      learning process can facilitate a bidirectional flow of ideas and content between
      teacher and students during a lecture to keep learners engaged and participating.

PMID- 28741652
TI  - A randomised, controlled trial of rectus sheath bupivacaine and intrathecal
      bupivacaine, without or with intrathecal morphine, vs. intrathecal bupivacaine
      and morphine after caesarean section.
AB  - We recruited 144 women of whom 131 underwent scheduled caesarean section and were
      allocated to intrathecal bupivacaine without (46) or with (47) morphine and
      postoperative rectus sheath bupivacaine; or intrathecal bupivacaine with morphine
      and postoperative rectus sheath saline (38). We measured postoperative pain with
      a 10-point numeric rating scale. The mean (SD) areas under the curve for pain on
      movement during 48 postoperative hours were 273.5 (63.6), 223.8 (80.7) and 223.8
      (80.7), respectively, p = 0.008. There was no difference between women who had
      intrathecal morphine with or without rectus sheath bupivacaine, p = 1. The
      equivalent values for pain at rest were 160.8 (64.7), 85.8 (79.4) and 82.8
      (74.3), respectively, p < 0.001. There was no difference between women who had
      intrathecal morphine with or without rectus sheath bupivacaine, p = 0.98.

PMID- 28741653
TI  - A randomised controlled trial of oral chloral hydrate vs. intranasal
      dexmedetomidine before computerised tomography in children.
AB  - Chloral hydrate is commonly used to sedate children for painless procedures.
      Children may recover more quickly after sedation with dexmedetomidine, which has
      a shorter half-life. We randomly allocated 196 children to chloral hydrate syrup
      50 mg.kg-1 and intranasal saline spray, or placebo syrup and intranasal
      dexmedetomidine spray 3 MUg.kg-1 , 30 min before computerised tomography studies.
      More children resisted or cried after drinking chloral hydrate syrup than placebo
      syrup, 72 of 107 (67%) vs. 42 of 87 (48%), p = 0.009, but there was no difference
      after intranasal saline vs. dexmedetomidine, 49 of 107 (46%) vs. 40 of 87 (46%),
      p = 0.98. Sedation was satisfactory in 81 of 107 (76%) children after chloral
      hydrate and 64 of 87 (74%) children after dexmedetomidine, p = 0.74. Of the 173
      children followed up for at least 4 h after discharge, 38 of 97 (39%) had
      recovered normal function after chloral hydrate and 32 of 76 (42%) after
      dexmedetomidine, p = 0.76. Six children vomited after chloral hydrate syrup and
      placebo spray vs. none after placebo syrup and dexmedetomidine spray, p = 0.03.

PMID- 28741654
TI  - The IADPSG diagnostic criteria identify women with increased risk of adverse
      pregnancy outcomes in Victoria.
AB  - Controversy remains surrounding International Association of Diabetes and
      Pregnancy Study Group (IADPSG) diagnostic criteria for gestational diabetes
      mellitus (GDM), including perceived improvement in perinatal outcomes and health
      service implications. We compared perinatal outcomes for untreated women meeting
      IADPSG-only criteria and women without GDM in Victoria. Women meeting IADPSG-only
      criteria were characterised according to fasting and one hour glucose thresholds
      and by region of birth. IADPSG criteria identified women with increased risk of
      adverse perinatal outcomes, particularly women born in Australia compared to
      Asian regions.

PMID- 28741655
TI  - Treatment of a thyrotropin-secreting pituitary adenoma (TSH-oma) with pasireotide
      LAR.

PMID- 28741656
TI  - Biochemical evaluation of storage lesion in canine packed erythrocytes.
AB  - OBJECTIVES: To describe the biochemical changes - also known as the storage
      lesion - that occur in canine packed red blood cells during ex vivo storage.
      MATERIALS AND METHODS: Ten 125-mL units of non-leuco-reduced packed red blood
      cells in citrate phosphate dextrose adenine were obtained from a commercial blood
      bank within 24 hours of donation. Samples were aseptically collected on days 1,
      4, 7, 14, 28, 35 and 42 for measurement of sodium, potassium, chloride, lactate,
      glucose, pH and ammonia concentrations. All units were cultured on day 42.
      Friedman's repeated measures test with Dunn's multiple comparison test was used
      for non-parametric data. A repeated-measures analysis of variance with Tukey's
      multiple comparison test was used for parametric data. Alpha was set to 0.05.
      RESULTS: All analytes changed significantly during storage. The mean ammonia on
      day 1 (58.14 g/dL) was significantly lower (P<0.05) than those on days 28 (1266
      g/dL), 35 (1668 g/dL) and 42 (1860 g/dL). A significant increase in median
      lactate concentration over time was also observed, with day 1 (4.385 mmol/L)
      being significantly less (P<0.05) than days 14 (19.82 mmol/L), 21 (22.81 mmol/L),
      35 (20.31 mmol/L) and 42 (20.81 mmol/L). Median pH was significantly decreased
      after day 7. All bacterial cultures were negative. CLINICAL SIGNIFICANCE: Many
      biochemical alterations occur in stored canine packed red blood cells, although
      further studies are required to determine their clinical importance.

PMID- 28741658
TI  - Atrogin-1 increases smooth muscle contractility through myocardin degradation.
      Pavneet Singh, Dong Li, Yu Gui, Xi-Long Zheng.

PMID- 28741660
TI  - Is Overimitation a Uniquely Human Phenomenon? Insights From Human Children as
      Compared to Bonobos.
AB  - Imitation is a key mechanism of human culture and underlies many of the
      intricacies of human social life, including rituals and social norms. Compared to
      other animals, humans appear to be special in their readiness to copy novel
      actions as well as those that are visibly causally irrelevant. This study
      directly compared the imitative behavior of human children to that of bonobos,
      our understudied great ape relatives. During an action-copying task involving
      visibly causally irrelevant actions, only 3- to 5-year-old children (N = 77)
      readily copied, whereas no bonobo from a large sample did (N = 46). These results
      highlight the distinctive nature of the human cultural capacity and contribute
      important insights into the development and evolution of human cultural
      behaviors.

PMID- 28741661
TI  - Effect of dietary resveratrol supplementation on meat quality, muscle
      antioxidative capacity and mitochondrial biogenesis of broilers.
AB  - BACKGROUND: The naturally occurring polyphenol resveratrol has been acknowledged
      with many beneficial biological effects. The aim of this study was to evaluate
      the influence of dietary resveratrol supplementation on meat quality, muscle
      antioxidative capacity and mitochondrial biogenesis of broilers. One hundred and
      eighty 21-day-old male Cobb broilers were randomly assigned to two groups and fed
      on a 0 mg kg-1 or 400 mg kg-1 resveratrol-supplemented diet for 21 days. Then,
      chickens were slaughtered and pectoralis major muscle (PM) samples were collected
      for analysis. RESULTS: The results showed that resveratrol not only tended to
      increase (P < 0.10) PM pH24h but also significantly decreased (P < 0.05) PM
      L*45min , pH decline, drip loss and lactate content. Meanwhile, PM total
      antioxidative capacity and catalase activity were significantly increased (P <
      0.05) by resveratrol, while malondialdehyde content was decreased (P < 0.10).
      Moreover, resveratrol significantly increased (P < 0.05) PM peroxisome
      proliferator-activated receptor gamma coactivator 1alpha and nuclear respiratory
      factor 1 mRNA levels, along with increased (P < 0.05) citrate synthase activity.
      CONCLUSION: Resveratrol can be used as a feed additive to improve meat quality of
      broilers, which may be associated with improved muscle antioxidative status and
      mitochondrial biogenesis. (c) 2017 Society of Chemical Industry.

PMID- 28741662
TI  - Molecular breakdown: a comprehensive view of anaplastic lymphoma kinase (ALK)
      rearranged non-small cell lung cancer.
AB  - Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers
      (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK
      rearranged NSCLC patients show various primary responses with unknown reasons.
      Previous studies focused on the clinical aspects of ALK fusions in small cohorts,
      or were conducted in vitro and/or in vivo to investigate the function of ALK. One
      of the suggested theories describes how echinoderm microtubule-associated protein
      like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK
      inhibitors. Until now, there has been no integrated comprehensive study that
      dissects ALK at the molecular level in a large scale. Here, we report the largest
      extensive molecular analysis of 158 ALK-rearranged NSCLCs and have investigated
      these findings in a cell line construct experiment. We discovered that NSCLCs
      with EML4-ALK short forms (variant 3/others) had more advanced stage and frequent
      metastases than cases with the long forms (variant 1/others) (p = 0.057, p <
      0.05). In vitro experiments revealed that EML4-ALK short forms show lower
      sensitivity to ALK inhibitors than do long forms. Clinical analysis also showed a
      trend for the short forms showing worse PFS. Interestingly, we found that
      breakpoints of ALK are evenly distributed mainly in intron 19 and almost all of
      them undergo a non-homologous end-joining repair to generate ALK fusions. We also
      discovered four novel somatic ALK mutations in NSCLC (T1151R, R1192P, A1280V, and
      L1535Q) that confer primary resistance; all of them showed strong resistance to
      ALK inhibitors, as G1202R does. Through targeted deep sequencing, we discovered
      three novel ALK fusion partners (GCC2, LMO7, and PHACTR1), and different ALK
      fusion partners showed different intracellular localization. With our findings
      that the EML4-ALK variants, new ALK somatic mutations, and novel ALK-fusion
      partners may affect sensitivity to ALK inhibitors, we stress the importance of
      targeted therapy to take the ALK molecular profiling into consideration.
      Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 28741663
TI  - Carbon Dioxide Flush of an Integrated Minimized Perfusion Circuit Prior to
      Priming Prevents Spontaneous Air Release Into the Arterial Line During Clinical
      Use.
AB  - Recently, an oxygenator with an integrated centrifugal blood pump (IP) was
      designed to minimize priming volume and to reduce blood foreign surface contact
      even further. The use of this oxygenator with or without integrated arterial
      filter was compared with a conventional oxygenator and nonintegrated centrifugal
      pump. To compare the air removal characteristics 60 patients undergoing coronary
      artery bypass grafting were alternately assigned into one of three groups to be
      perfused with a minimized extracorporeal circuit either with the conventional
      oxygenator, the oxygenator with IP, or the oxygenator with IP plus integrated
      arterial filter (IAF). Air entering and leaving the three devices was measured
      accurately with a bubble counter during cardiopulmonary bypass. No significant
      differences between all groups were detected, considering air entering the
      devices. Our major finding was that in both integrated devices groups incidental
      spontaneous release of air into the arterial line in approximately 40% of the
      patients was observed. Here, detectable bolus air (>500 um) was shown in the
      arterial line, whereas in the minimal extracorporeal circulation circuit (MECC)
      group this phenomenon was not present. We decided to conduct an amendment of the
      initial design with METC-approval. Ten patients were assigned to be perfused with
      an oxygenator with IP and IAF. Importantly, the integrated perfusion systems used
      in these patients were flushed with carbon dioxide (CO2 ) prior to priming of the
      systems. In the group with CO2 flush no spontaneous air release was observed in
      all cases and this was significantly different from the initial study with the
      group with the integrated device and IAF. This suggests that air spilling may be
      caused by residual air in the integrated device. In conclusion, integration of a
      blood pump may cause spontaneous release of large air bubbles (>500 um) into the
      arterial line, despite the presence of an integrated arterial filter. CO2
      flushing of an integrated cardiopulmonary bypass system prior to priming may
      prevent spontaneous air release and is strongly recommended to secure patient
      safety.

PMID- 28741664
TI  - In Vitro Evaluation of an Immediate Response Starling-Like Controller for Dual
      Rotary Blood Pumps.
AB  - Rotary ventricular assist devices (VADs) are used to provide mechanical
      circulatory support. However, their lack of preload sensitivity in constant speed
      control mode (CSC) may result in ventricular suction or venous congestion. This
      is particularly true of biventricular support, where the native flow-balancing
      Starling response of both ventricles is diminished. It is possible to model the
      Starling response of the ventricles using cardiac output and venous return
      curves. With this model, we can create a Starling-like physiological controller
      (SLC) for VADs which can automatically balance cardiac output in the presence of
      perturbations to the circulation. The comparison between CSC and SLC of dual
      HeartWare HVADs using a mock circulation loop to simulate biventricular heart
      failure has been reported. Four changes in cardiovascular state were simulated to
      test the controller, including a 700 mL reduction in circulating fluid volume, a
      total loss of left and right ventricular contractility, reduction in systemic
      vascular resistance ( SVR) from 1300 to 600 dyne  s/cm5, and an elevation in
      pulmonary vascular resistance ( PVR) from 100 to 300 dyne  s/cm5. SLC maintained
      the left and right ventricular volumes between 69-214 mL and 29-182 mL,
      respectively, for all tests, preventing ventricular suction (ventricular volume =
      0 mL) and venous congestion (atrial pressures > 20 mm Hg). Cardiac output was
      maintained at sufficient levels by the SLC, with systemic and pulmonary flow
      rates maintained above 3.14 L/min for all tests. With the CSC, left ventricular
      suction occurred during reductions in SVR, elevations in PVR, and reduction in
      circulating fluid simulations. These results demonstrate a need for a
      physiological control system and provide adequate in vitro validation of the
      immediate response of a SLC for biventricular support.

PMID- 28741665
TI  - Remote Ischemic Preconditioning and Clinical Outcomes in On-Pump Coronary Artery
      Bypass Grafting: A Meta-Analysis of 14 Randomized Controlled Trials.
AB  - The purpose of this article is to perform the first pooled analysis on remote
      ischemic preconditioning (RIPC) used for the improvement of clinical outcomes of
      patients only undergoing on-pump coronary artery bypass grafting (CABG) in
      randomized controlled trials (RCTs). A systematic search was performed using
      PubMed, the Cochrane Library, and the Web of Science to identify studies that
      described the effect of RIPC on postoperative mortality in patients only
      undergoing on-pump CABG. The outcomes included postoperative mortality,
      postoperative morbidity (including incidence of myocardial infarction, atrial
      fibrillation, stroke, acute kidney injury, and renal replacement therapy),
      mechanical ventilation (MV), intensive care unit length of stay (ICU LOS), and
      hospital length of stay (HLOS). A total of 14 RCTs (2830 participants) were
      included. Our meta-analysis found that RIPC failed to reduce the postoperative
      mortality in patients only undergoing on-pump CABG compared with control
      individuals (odds ratio, 0.81; 95% confidence interval, [0.40, 1.64]; P = 0.55;
      I2  = 25%). Moreover, there were no differences in postoperative morbidity, ICU
      LOS, and HLOS between the two groups. However, MV in the RIPC group was shorter
      than that in control individuals (standard mean difference, -0.41; 95% confidence
      interval, [-0.80, -0.01]; P = 0.04; I2  = 73%). The present meta-analysis found
      that RIPC failed to improve most of clinical outcomes in patients only undergoing
      on-pump CABG; however, MV was reduced. Adequately powered trials are warranted to
      provide more evidence in the future.

PMID- 28741666
TI  - Assessment of the potential of the multi-enzyme producer Bacillus
      amyloliquefaciens US573 as alternative feed additive.
AB  - BACKGROUND: Recently, probiotics have increasingly been used as feed additives in
      poultry diets as an alternative to antibiotic growth promoters fostering
      resistance development. RESULTS: This study was aimed at assessing the potential
      of Bacillus amyloliquefaciens US573 as a direct-fed microbial. The US573 strain
      was found to be free of harmful enzymatic activities and sensitive to
      antibiotics. In addition, it showed a good acid and bovine bile tolerance, high
      adhesion efficacy to chicken enterocytes, and an ability to form biofilms, which
      may favor its survival and persistence in the animal gastrointestinal tract.
      Moreover, besides the previously described extremely salt-tolerant and highly
      thermostable phytase, the US573 strain secretes xylanase, beta-glucanase and
      amylase activities useful in neutralizing antinutritional factors and maximizing
      the absorption of nutrients. The secretion of such enzymes may be responsible for
      the good performance of the US573 isolate in the digestibility of wheat in vitro.
      Indeed, using the vegetative cells, a yield of wheat dry matter digestibility of
      approximately 48% was achieved, which is slightly lower than the commercial feed
      additive Rovabio used as a reference (56.73% digestibility). CONCLUSION: The
      obtained results illustrate the potential of US573 strain as a promising direct
      fed microbial candidate for application in the poultry industry. (c) 2017 Society
      of Chemical Industry.

PMID- 28741667
TI  - An evaluation of the validity of the pre-operative oxygen uptake efficiency slope
      as an indicator of cardiorespiratory fitness in elderly patients scheduled for
      major colorectal surgery.
AB  - This study aimed to investigate the validity of the oxygen uptake efficiency
      slope as an objective and submaximal indicator of cardiorespiratory fitness in
      elderly patients scheduled for major colorectal surgery. Patients >= 60 years of
      age, with a metabolic equivalent score using the Veterans Activity Questionnaire
      <= 7 and scheduled for major colorectal surgery participated in a pre-operative
      cardiopulmonary exercise test. The oxygen uptake efficiency slope was calculated
      up to different exercise intensities, using 100%, 90% and 80% of the exercise
      data. Data from 71 patients (47 men, mean (SD) age 75.2 (6.7) years) were
      analysed. The efficiency slope obtained from all the data was statistically
      significantly different from the values when 90% (p = 0.027) and 80% (p = 0.023)
      of the data were used. The 90% and 80% values did not differ significantly from
      each other (p = 0.152). Correlations between the oxygen uptake efficiency slope
      and the peak oxygen uptake ranged from 0.816 to 0.825 (all p < 0.001), and
      correlations between oxygen uptake efficiency slope and the ventilatory anaerobic
      threshold ranged from 0.793 to 0.805 (all p < 0.001). Receiver operating
      characteristic curves showed that the oxygen uptake efficiency slope is a
      sensitive and specific predictor of a peak oxygen uptake <= 18.2 ml.kg-1 .min-1 ,
      with an area under the curve (95%CI) of 0.876 (0.780-0.972, p < 0.001) and a
      ventilatory anaerobic threshold <= 11.1 ml.kg-1 .min-1 , with an area under the
      curve (95%CI) of 0.828 (0.726-0.929, p < 0.001). These correlations suggest that
      the oxygen uptake efficiency slope provides a valid (sub)maximal measure of
      cardiorespiratory fitness in these patients, and the predictive ability described
      indicates that it might help discriminate patients at higher risk of
      postoperative morbidity. However, future research should investigate the
      prognostic value of the oxygen uptake efficiency slope for postoperative
      outcomes.

PMID- 28741668
TI  - Pharmacokinetics of deflazacort in rabbits after intravenous and oral
      administration and its interaction with erythromycin.
AB  - The pharmacokinetic of deflazacort after intravenous and oral administration and
      the effect of erythromycin on the disposition of deflazacort in rabbits were
      investigated. A parallel study was carried out in twelve rabbits. The plasma
      concentration-time profiles of deflazacort were determined after intravenous and
      oral administration of single dosages of 5 mg/kg in the presence and absence
      (baseline) of multiple dose erythromycin regimens. Plasma concentrations of 21
      desacetyldeflazacort were determined by HPLC. Plasma concentration-time curves
      were analysed by compartmental pharmacokinetic and noncompartmental methods. The
      t1/2lambdaz values following intravenous and oral administration were 3.67 and
      4.96 hr, respectively. The apparent volume of distribution at steady-state (Vss )
      was 4.08 +/- 0.31 L/kg, this value indicates that deflazacort is widely
      distributed into the extravascular tissues. Moreover, bioavailability after oral
      administration of deflazacort (F = 87.48%) was high. Pharmacokinetic analysis
      after both routes of administration revealed a significant reduction in total
      body clearance, a significant increase in mean residence time, half-life and
      plasma concentrations of the steroid in the presence of multiple dose
      erythromycin. The results indicated the influence of the erythromycin on
      deflazacort disposition, which is consistent with a pharmacokinetic-type
      interaction in the elimination of the drug from the body. Moreover, this
      interaction should be considered to avoid adverse effects when using both drugs
      concomitantly.

PMID- 28741669
TI  - Connecting salt stress signalling pathways with salinity-induced changes in
      mitochondrial metabolic processes in C3 plants.
AB  - Salinity exerts a severe detrimental effect on crop yields globally. Growth of
      plants in saline soils results in physiological stress, which disrupts the
      essential biochemical processes of respiration, photosynthesis, and
      transpiration. Understanding the molecular responses of plants exposed to
      salinity stress can inform future strategies to reduce agricultural losses due to
      salinity; however, it is imperative that signalling and functional response
      processes are connected to tailor these strategies. Previous research has
      revealed the important role that plant mitochondria play in the salinity response
      of plants. Review of this literature shows that 2 biochemical processes required
      for respiratory function are affected under salinity stress: the tricarboxylic
      acid cycle and the transport of metabolites across the inner mitochondrial
      membrane. However, the mechanisms by which components of these processes are
      affected or react to salinity stress are still far from understood. Here, we
      examine recent findings on the signal transduction pathways that lead to adaptive
      responses of plants to salinity and discuss how they can be involved in and be
      affected by modulation of the machinery of energy metabolism with attention to
      the role of the tricarboxylic acid cycle enzymes and mitochondrial membrane
      transporters in this process.

PMID- 28741670
TI  - Intensive cognitive therapy for post-traumatic stress disorder in routine
      clinical practice: A matched comparison audit.
AB  - OBJECTIVES: Intensive cognitive therapy for post-traumatic stress disorder (PTSD)
      has been shown to be as effective as weekly treatment in controlled trials. In
      this study, outcome data comparing standard and intensive treatments delivered in
      routine clinical practice were analysed. METHODS: A consecutive case series of
      intensive treatment cases were compared to matched control cases who had
      completed weekly treatment. RESULTS: Both groups showed significant improvements
      on PTSD and depression measures. The intensive group showed larger PTSD
      symptomatic improvement. There were differences between the groups in age and
      time since trauma, suggesting selection biases in who is offered, and/or who
      chooses intensive treatment. CONCLUSIONS: For some individuals, an intensive
      format may be more effective than weekly treatment.

PMID- 28741671
TI  - The Impact of FOXP3 Polymorphism on the Risk of Allergic Rhinitis: A Meta
      Analysis.
AB  - Polymorphisms of several genes were reported to be associated with the risk of
      allergic rhinitis. Here, we first conducted a meta-analysis to evaluate the
      potential genetic association between the polymorphisms of the FOXP3 (Forkhead
      Box P3) gene and the susceptibility to allergic rhinitis. A total of 2671
      relevant articles were initially retrieved from the databases of PubMed, Web of
      Science, Embase, WANFANG/CNKI and Scopus, and six eligible case-control studies
      were finally enrolled in our meta-analysis, according to our strict
      inclusion/exclusion criteria. Based on the extracted data, Mantel-Haenszel
      statistic, Cochrane's Q statistic, I2 test, subgroup meta-analysis, Begg's test,
      Egger's test and sensitivity analysis were performed via Stata/SE 12.0 software.
      The results of the Mantel-Haenszel statistic regarding rs3761548 showed that no
      significant difference was observed in the allergic rhinitis case and population
      based control group under the genetic models of A versus C, AA versus CC, CA+AA
      versus CC, AA versus CC+CA and carrier A versus C (all P-value of Association
      Test, PA > 0.05), apart from CA versus CC (PA  =  0.020). The similar results
      were obtained in the subgroup analysis of Asian. In addition, we did not obtain
      the positive result in the meta-analysis of rs2232365 (all PA > 0.05). We also
      excluded the presence of large publication bias through Begg's test and Egger's
      test, and we confirmed the stability of data by sensitivity analysis. In summary,
      no significant association between rs3761548, rs2232365 polymorphisms of the
      FOXP3 gene, and an increased susceptibility to allergic rhinitis was identified
      based on the published data; however, this conclusion should be confirmed by more
      studies with increased sample sizes.

PMID- 28741672
TI  - Finding of increased caudate nucleus in patients with Alzheimer's disease.
AB  - OBJECTIVES: A recently published study using an automated MRI volumetry method
      (NeuroQuant(r)) unexpectedly demonstrated larger caudate nucleus volume in
      patients with Alzheimer's disease dementia (AD) compared to patients with
      subjective and mild cognitive impairment (SCI and MCI). The aim of this study was
      to explore this finding. MATERIALS & METHODS: The caudate nucleus and the
      hippocampus volumes were measured (both expressed as ratios of intracranial
      volume) in a total of 257 patients with SCI and MCI according to the Winblad
      criteria and AD according to ICD-10 criteria. Demographic data, cognitive
      measures, and APOE-E4 status were collected. RESULTS: Compared with non-dementia
      patients (SCI and MCI), AD patients were older, more of them were female, and
      they had a larger caudate nucleus volume and smaller hippocampus volume (P<.001).
      In multiple linear regression analysis, age and female sex were associated with
      larger caudate nucleus volume, but neither diagnosis nor memory function was.
      Age, gender, and memory function were associated with hippocampus volume, and age
      and memory function were associated with caudate nucleus/hippocampus ratio.
      CONCLUSIONS: A larger caudate nucleus volume in AD patients was partly explained
      by older age and being female. These results are further discussed in the context
      of (1) the caudate nucleus possibly serving as a mechanism for temporary
      compensation; (2) methodological properties of automated volumetry of this brain
      region; and (3) neuropathological alterations. Further studies are needed to
      fully understand the role of the caudate nucleus in AD.

PMID- 28741673
TI  - Eslicarbazepine acetate as adjunctive treatment in partial-onset epilepsy.
AB  - OBJECTIVE: The aim of the study was to assess the clinical response to
      eslicarbazepine acetate (ESL) as add-on therapy in adult patients with partial
      onset epilepsy by means of the time-to-baseline seizure count method. METHODS: We
      retrospectively identified consecutive patients with partial-onset seizures, with
      or without secondary generalization, prescribed to ESL add-on therapy. The
      primary endpoint was the time-to-baseline monthly seizure count. Subgroup
      analysis was performed according to carbamazepine (CBZ)/oxcarbazepine (OXC)
      status (prior vs never use). Secondary outcomes were the rate of treatment
      related adverse events (AEs) and the AEs affecting >=5% of patients. RESULTS: One
      hundred and eighteen patients were included. The median time-to-baseline monthly
      seizure count was 46 (35-101) days in the overall study cohort. The number of
      concomitant anti-epileptic drugs (AEDs) was associated with the time-to-endpoint
      (adjusted hazard ratio [adj HR]=2.22, 95% CI 1.18-4.14, P=.013 for two AEDs vs
      one; adj HR=3.65, 95% CI 1.66-8.06, P=.001 for three or more AEDs vs one).
      Groupwise, the median times-to-baseline seizure count were 47 (35-97) and 43 (34
      103) in patients with prior and never exposure to CBZ/OXC, respectively (P for
      log-rank test=.807). Adverse events occurred in 53.4% (63 of 118) of patients;
      the most frequently reported were dizziness (13.6%), somnolence (11.9%), nausea
      (6.8%), and fatigue (5.1%). CONCLUSIONS: Add-on ESL improved seizure control and
      was overall well-tolerated in adult patients with partial-onset epilepsy.

PMID- 28741674
TI  - Validation of and proposals for refinements of the WHO 2016 classification for
      myelodysplastic syndromes.

PMID- 28741675
TI  - Pharmacokinetics of dinalbuphine sebacate and nalbuphine in human after
      intramuscular injection of dinalbuphine sebacate in an extended-release
      formulation.
AB  - Nalbuphine is a semi-synthetic opioid indicated for the relief of moderate to
      severe pain. Its short half-life requires frequent injections in clinical
      practice, resulting in a greater incidence of adverse events. A prodrug of
      nalbuphine has been developed, dinalbuphine sebacate (DNS), dissolved in a simple
      oil-based injectable formulation, which could deliver and maintain an effective
      blood level of nalbuphine. An open-label, prospective, two-period study was
      performed in healthy volunteers to verify the extended blood concentration
      profile of nalbuphine. Twelve healthy Taiwanese were randomized to receive an
      intramuscular injection of 20 mg nalbuphine HCl and 150 mg DNS sequentially with
      a washout period of 5 days. To prevent DNS hydrolysis during sample analysis, the
      effect of four esterase inhibitors was evaluated in the quantitation of DNS in
      human whole blood and thenoyltrifluoroacetone was chosen. The bioavailability of
      nalbuphine from intramuscularly injected DNS relative to that from nalbuphine HCl
      was 85.4%. The mean absorption time of nalbuphine from DNS was 145.2 h. It took
      approximately 6 days for the complete release of DNS into the blood stream where
      DNS was rapidly hydrolysed to nalbuphine; suggesting a single injection of 150 mg
      DNS in our extended-release formulation could provide long-lasting pain relief.

PMID- 28741676
TI  - The association of abdominal muscle with outcomes after scheduled abdominal
      aortic aneurysm repair.
AB  - Sarcopenia is the degenerative loss of core muscle mass. It is an aspect of
      frailty, which is associated with increased rates of peri-operative harm. We
      assessed the association of the cross-sectional areas of abdominal muscles,
      including psoas, with survival during a median (IQR [range]) follow-up of 3.8
      (3.2-4.4 [0.0-5.1]) years after scheduled endovascular (132) or open (5)
      abdominal aortic aneurysm repair in 137 patients. In multivariate analysis,
      mortality hazard (95%CI) was independently associated with: age, 1.06 (1.01-1.13)
      per year, p = 0.03; and the adjusted area of the left psoas muscle, 0.94 (0.81
      1.01) per mm2 .kg-0.83 , p = 0.08. Shortened hospital stay was independently
      associated with haemoglobin concentration and adjusted left psoas muscle area,
      hazard ratio (95%) 1.01 (1.00-1.02) per g.l-1 and 1.05 (1.02-1.07) per mm2 .kg
      0.83 , p = 0.04 and 0.001, respectively.

PMID- 28741677
TI  - Kidney function of transfused children with sickle cell anemia: Baseline data
      from the TWiTCH study with comparison to non-transfused cohorts.

PMID- 28741678
TI  - Recent advances of microbial breeding via heavy-ion mutagenesis at IMP.
AB  - : Nowadays, the value of heavy-ion mutagenesis has been accepted as a novel
      powerful mutagen technique to generate new microbial mutants due to its high
      linear energy transfer and high relative biological effectiveness. This paper
      briefly reviews recent progress in developing a more efficient mutagenesis
      technique for microbial breeding using heavy-ion mutagenesis, and also presents
      the outline of the beam line for microbial breeding in Heavy Ion Research
      Facility of Lanzhou. Then, new insights into microbial biotechnology via heavy
      ion mutagenesis are also further explored. We hope that our concerns will give
      deep insight into microbial breeding biotechnology via heavy-ion mutagenesis. We
      also believe that heavy-ion mutagenesis breeding will greatly contribute to the
      progress of a comprehensive study industrial strain engineering for bioindustry
      in the future. SIGNIFICANCE AND IMPACT OF THE STUDY: There is currently a great
      interest in developing rapid and diverse microbial mutation tool for strain
      modification. Heavy-ion mutagenesis has been proved as a powerful technology for
      microbial breeding due to its broad spectrum of mutation phenotypes with high
      efficiency. In order to deeply understand heavy-ion mutagenesis technology, this
      paper briefly reviews recent progress in microbial breeding using heavy-ion
      mutagenesis at IMP, and also presents the outline of the beam line for microbial
      breeding in Heavy Ion Research Facility of Lanzhou (HIRFL) as well as new
      insights into microbial biotechnology via heavy-ion mutagenesis. Thus, this work
      can provide the guidelines to promote the development of novel microbial
      biotechnology cross-linking heavy-ion mutagenesis breeding that could make
      breeding process more efficiently in the future.

PMID- 28741679
TI  - Comparing social group identifications and socioeconomic deprivation as
      predictors of psychological distress: Evidence from a Scottish primary care
      sample.
AB  - Social group identification and socioeconomic deprivation have both been linked
      to self-reported depressive symptoms in general population samples; however, no
      study to date has explored the strength of the joint predictive value of these
      factors within a mental health population. The current study explored the impact
      of social group identifications and socioeconomic deprivation, together with
      important clinical and demographic variables, on psychological distress in a
      Scottish mental health sample. Participants (N = 976) were recruited from
      referrals to a computerized cognitive behavioural therapy (cCBT) programme in
      Scotland, 'Beating the Blues' (BtB) over a 25-month period. Participants
      completed the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM)
      as a measure of psychological distress and three versions of the group
      identifications scale (GIS), one for each of three groups: family, community, and
      a social group of choice. Demographic information and clinical information were
      collected on commencing BtB. Higher numbers of group identifications were
      significantly associated with lower psychological distress. Additionally,
      increased socioeconomic deprivation was significantly associated with more severe
      psychological distress; however, interestingly, the association was not as strong
      as that of group identifications. Identifying with fewer social groups predicts
      more severe psychological symptom presentations, even more so than living in a
      greater state of socioeconomic deprivation.

PMID- 28741680
TI  - Evaluating social (pragmatic) communication disorder.
AB  - BACKGROUND: Social (pragmatic) communication disorder (SPCD) is a new diagnosis
      introduced by DSM-5, characterised by problems with verbal and nonverbal social
      communication. It is currently unclear whether SPCD is a valid diagnostic
      category, because little is known about the characteristics of those who meet its
      criteria. We sought to identify and describe cases of SPCD, to contribute to
      debates about its validity. We investigated whether the symptoms of SPCD cluster
      together to form a coherent syndrome that is distinct from autism spectrum
      disorder (ASD) in terms of its core and associated features. METHODS:
      Participants were young people (N = 1,081, age range = 4-18 years) who had
      attended a specialist social communication disorders clinic for children with
      fluent language and normal-range intelligence. Standardised parent-report data
      were collected using the Developmental, Dimensional and Diagnostic Interview
      (3Di), Child Communication Checklist (CCC) and Strengths and Difficulties
      Questionnaire (SDQ). An algorithm was designed using 3Di and CCC items to
      implement DSM-5 SPCD criteria. RESULTS: Eighty-eight young people met our
      criteria for SPCD, with 801 meeting DSM-5 ASD criteria and the remaining 192
      having neither SPCD nor ASD ('clinical comparison group'). The core symptoms of
      SPCD co-occurred to a moderate degree (average interitem correlation = .22). SPCD
      cases had autistic social difficulties that were intermediate between ASD and the
      clinical comparison group. SPCD was associated with high rates of nonautistic
      psychopathology, with 63.5% scoring in the abnormal range of the SDQ's Total
      Problems scale. CONCLUSIONS: We did not find evidence that SPCD is qualitatively
      distinct from ASD. Rather, it appears to lie on the borderlands of the autism
      spectrum, describing those with autistic traits that fall just below the
      threshold for an ASD diagnosis. SPCD may have clinical utility for identifying
      people with autistic traits that are insufficiently severe for ASD diagnosis, but
      who nevertheless require support.

PMID- 28741681
TI  - Climatic potential for summer and winter wine production.
AB  - BACKGROUND: The geoviticultural multicriteria climatic classification (MCC)
      system provides an efficient guide for assessing the influence of climate on wine
      varieties. Parana is one of the three states in southern Brazil that has great
      potential for the expansion of wine production, mainly due to the conditions that
      favour two harvests a year. The objective was to apply the geoviticultural MCC
      system in two production seasons. We used maximum, mean and minimum air
      temperature and precipitation for 1990-2015 for the state of Parana. Air
      temperature and Precipitation were used to calculate the evapotranspiration and
      water balance. We applied the MCC system to identify potential areas for
      grapevine production for harvests in both summer and winter and then determined
      the climatic zones for each geoviticultural climate. RESULTS: Parana has
      viticultural climates with conditions favourable for grapevine cultivation for
      the production of fine wines from summer and winter harvests. The conditions for
      the winter harvest provided wines with good coloration and high aromatic
      potential relative to the summer harvest. CONCLUSION: Chardonnay, Merlot, Pinot
      Blanc and Muller-Thurgau were suitable for regions with lower air temperatures
      and water deficits. Pinot Blanc and Muller-Thurgau were typical for the southern
      region of Parana. (c) 2017 Society of Chemical Industry.

PMID- 28741682
TI  - Strengthening the laboratory diagnosis of pathogenic Corynebacterium species in
      the Vaccine era.
AB  - Over the last three decades, successful implementation of the diphtheria
      vaccination in the developed and developing countries has reduced the infections
      caused by the toxigenic strains of Corynebacterium diphtheriae, but a concomitant
      increase in the invasive infections due to the nontoxigenic strains was seen. In
      addition, the recent reports on the emergence of nontoxigenic toxin gene-bearing
      strains, having the potential to revert back to toxigenic form poses a
      significant threat to human beings. Besides infections caused by C. diphtheriae,
      the emergence of the respiratory, cutaneous and invasive infections by related
      pathogenic Corynebacterium species like C. ulcerans and C. pseudotuberculosis,
      complicate the diagnosis and management of infection. These observations together
      with the widespread prevalence of diphtheria in the vaccine era, necessitates the
      strengthening of the epidemiological surveillance and laboratory diagnosis of the
      pathogen. This review provides the overview of the advantages and limitations of
      different molecular methods and the role of MALDI-TOF in the laboratory diagnosis
      of Diphtheria. The contribution of next generation sequencing technology and
      different genotyping techniques in understanding the pathogenicity, transmission
      dynamics and epidemiology of the C. diphtheriae is discussed.

PMID- 28741683
TI  - A clinical trial of a novel emulsion for potential use as a saliva substitute in
      patients with radiation-induced xerostomia.
AB  - Researchers have recently developed a novel oily formulation for potential use as
      a saliva substitute for the treatment of dry mouth. The aim of this randomised,
      crossover study was to compare this new formulation to a currently available
      saliva substitute and a control of water on measures of mastication, subjective
      feeling of oral dryness and product acceptability. Forty participants treated
      with radiotherapy to the head and neck and experiencing xerostomia were invited
      to participate in the trial. Each participant trialled all three products in a
      randomised order. The effect of each product was measured using the Test of
      Masticating and Swallowing Solids (TOMASS), the Shortened Xerostomia Inventory
      (SXI) and a questionnaire designed to test patient acceptability of each product.
      Outcome data were gathered in a single session after the first administration of
      each product to evaluate immediate effects and after 7 days of use to evaluate
      longer-term effects. Statistical analyses consisted of repeated-measures analysis
      of variance and mixed models. There was no evidence that application of the three
      formulations had an effect on any of the TOMASS measures, either immediately or
      after one week of use (P > 0.05). There was a significant main effect of
      formulation on the SXI score (P = 0.02). Application of the novel emulsion
      resulted in a clinically small but significant improvement in SXI score (P <
      0.01); however, application of methylcellulose (P = 0.21) and water (P = 0.81)
      resulted in no significant difference. There was no difference in participant
      acceptability between the three products (P = 0.32). The novel oily emulsion
      showed no clinically significant benefit over two existing products for relief of
      xerostomia. Indeed, none of the three products demonstrated significant change in
      patient outcomes.

PMID- 28741684
TI  - How does mandibular bone atrophy influence the masticatory function, OHRQoL and
      satisfaction in overdenture wearers? Clinical results until 1-year post-loading.
AB  - This longitudinal clinical study investigated the differences in the masticatory
      function (MF), satisfaction and oral health-related quality of life (OHRQoL)
      between atrophic patients (AP) and non-atrophic patients (NAP) before and after
      rehabilitation with mandibular overdenture (MO). Twenty-six complete denture (CD)
      wearers were categorised into two groups, according to the mandibular bone
      atrophy (MBA) degree. MF was evaluated before and after 1, 3, 6 and 12 months of
      the MO loading via 2 standardised tests: (i) MP, masticatory performance (MP_X50,
      MPB, ME 5.6, ME 2.8) and (ii) ST, swallowing threshold (time, number of cycles,
      ST_X50, STB, ME 5.6, ME 2.8). The dental impact on daily living (DIDL)
      questionnaire measured changes in the satisfaction level and OHRQoL. MP
      comparisons showed significant difference only for ME 5.6 12 months after MO
      loading (AP=33.79 +/- 23.6; NAP=17.58 +/- 20.1). ST presented significant
      differences before MO loading for: ST_X50 (AP=5.48 +/- 0.83; NAP=4.31 +/- 1.44),
      ME 5.6 (AP=53.17 +/- 24.71; NAP=29.83 +/- 31.45) and ME 2.8 (AP=8.76 +/- 6.91;
      NAP=18.61 +/- 10.71). One month after MO loading, NAP performed the ST test 21%
      faster than AP. After 3 months, significant improvements in STB (AP=4.93 +/-
      4.82; NAP=2.73 +/- 1.27) and ME 2.8 (AP=17.15 +/- 10.00; NAP=24.69 +/- 7.82) also
      were observed. DIDL evaluation showed significant differences in the oral comfort
      domain after 3 months (AP=0.66 +/- 0.29; NAP=0.87 +/- 0.16) and after 6 months
      (AP=0.79 +/- 0.22; NAP=0.98 +/- 0.08), with lower satisfaction levels in the AP.
      MBA negatively affects the MF mainly the ST. After 6 months, differences between
      AP and NAP disappeared and ST results were equalised. AP initially has lower
      satisfaction levels reaching similar levels of satisfaction as NAP after 1 year.

PMID- 28741685
TI  - Missing in action - where have all the data gone!?

PMID- 28741686
TI  - GPR55 receptor antagonist decreases glycolytic activity in PANC-1 pancreatic
      cancer cell line and tumor xenografts.
AB  - The Warburg effect is a predominant metabolic pathway in cancer cells
      characterized by enhanced glucose uptake and its conversion to l-lactate and is
      associated with upregulated expression of HIF-1alpha and activation of the EGFR
      MEK-ERK, Wnt-beta-catenin, and PI3K-AKT signaling pathways. (R,R')-4'-methoxy-1
      naphthylfenoterol ((R,R')-MNF) significantly reduces proliferation, survival, and
      motility of PANC-1 pancreatic cancer cells through inhibition of the GPR55
      receptor. We examined (R,R')-MNF's effect on glycolysis in PANC-1 cells and
      tumors. Global NMR metabolomics was used to elucidate differences in the
      metabolome between untreated and (R,R')-MNF-treated cells. LC/MS analysis was
      used to quantify intracellular concentrations of beta-hydroxybutyrate, carnitine,
      and l-lactate. Changes in target protein expression were determined by Western
      blot analysis. Data was also obtained from mouse PANC-1 tumor xenografts after
      administration of (R,R')-MNF. Metabolomics data indicate that (R,R')-MNF altered
      fatty acid metabolism, energy metabolism, and amino acid metabolism and increased
      intracellular concentrations of beta-hydroxybutyrate and carnitine while reducing
      l-lactate content. The cellular content of phosphoinositide-dependent kinase-1
      and hexokinase 2 was reduced consistent with diminished PI3K-AKT signaling and
      glucose metabolism. The presence of the GLUT8 transporter was established and
      found to be attenuated by (R,R')-MNF. Mice treated with (R,R')-MNF had
      significant accumulation of l-lactate in tumor tissue relative to vehicle-treated
      mice, together with reduced levels of the selective l-lactate transporter MCT4.
      Lower intratumoral levels of EGFR, pyruvate kinase M2, beta-catenin, hexokinase
      2, and p-glycoprotein were also observed. The data suggest that (R,R')-MNF
      reduces glycolysis in PANC-1 cells and tumors through reduced expression and
      function at multiple controlling sites in the glycolytic pathway.

PMID- 28741687
TI  - A distinct plasma lipid signature associated with poor prognosis in castration
      resistant prostate cancer.
AB  - Lipids are known to influence tumour growth, inflammation and chemoresistance.
      However, the association of circulating lipids with the clinical outcome of
      metastatic castration-resistant prostate cancer (CRPC) is unknown. We
      investigated associations between the plasma lipidome and clinical outcome in
      CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was
      performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients.
      Results were validated in an independent Phase 2 cohort of 63 CRPC patients.
      Unsupervised analysis of lipidomic profiles (323 lipid species) classified the
      Phase 1 cohort into two patient subgroups with significant survival differences
      (HR 2.31, 95% CI 1.44-3.68, p = 0.0005). The levels of 46 lipids were
      individually prognostic and were predominantly sphingolipids with higher levels
      associated with poor prognosis. A prognostic three-lipid signature was derived
      (ceramide d18:1/24:1, sphingomyelin d18:2/16:0, phosphatidylcholine 16:0/16:0)
      and was also associated with shorter survival in the Phase 2 cohort (HR 4.8, 95%
      CI 2.06-11.1, p = 0.0003). The signature was an independent prognostic factor
      when modelled with clinicopathological factors or metabolic characteristics. The
      association of plasma lipids with CRPC prognosis suggests a possible role of
      these lipids in disease progression. Further research is required to determine if
      therapeutic modulation of the levels of these lipids by targeting their metabolic
      pathways may improve patient outcome.

PMID- 28741688
TI  - New insights into naevoid melanomas: a clinicopathological reassessment.
AB  - AIMS: Because the term 'naevoid melanoma' has variable clinical and pathological
      interpretations, we aimed to clarify the features of melanomas referred to as
      naevoid. METHODS AND RESULTS: A review was undertaken of 102 melanomas diagnosed
      histopathologically as naevoid melanomas and ascertained by European Organization
      for Research and Treatment of Cancer Melanoma Group Subcommittee pathologists
      from their records. We found these could be classified morphologically into three
      groups. Thirteen melanomas were overlying genuine naevi and were therefore
      excluded. Of the 89 melanomas considered to be naevoid, 11 presented clinically
      as exophytic papillomatous nodules with little junctional component and composed
      of small atypical cells showing numerous mitoses and no change with depth; we
      termed these 'papillomatous naevoid' melanomas. The other 78 were flat or only
      slightly raised, and had a superficial spreading melanoma-like component with
      maturation to a small cell, but still an atypical, dermal component; we termed
      these 'maturing naevoid' melanomas. We showed that papillomatous and maturing
      naevoid melanomas also have differing immunochemical profiles. Preliminary
      clinical follow-up suggested different outcomes for these two naevoid melanoma
      types. CONCLUSIONS: Melanomas that have been classified as naevoid melanomas
      comprise two types with distinct clinical, histopathological and
      immunohistochemical features that may also be prognostically significant.

PMID- 28741689
TI  - Superparamagnetic Gold Nanoparticles Synthesized on Protein Particle Scaffolds
      for Cancer Theragnosis.
AB  - Cancer theragnosis using a single multimodality agent is the next mainstay of
      modern cancer diagnosis, treatment, and management, but a clinically feasible
      agent with in vivo cancer targeting and theragnostic efficacy has not yet been
      developed. A new type of cancer theragnostic agent is reported, based on gold
      magnetism that is induced on a cancer-targeting protein particle carrier.
      Superparamagnetic gold-nanoparticle clusters (named SPAuNCs) are synthesized on a
      viral capsid particle that is engineered to present peptide ligands targeting a
      tumor cell receptor (TCR). The potent multimodality of the SPAuNCs is observed,
      which enables TCR-specific targeting, T2 -weighted magnetic resonance imaging,
      and magnetic hyperthermia therapy of both subcutaneous and deep-tissue tumors in
      live mice under an alternating magnetic field. Furthermore, it is analytically
      elucidated how the magnetism of the SPAuNCs is sufficiently induced between
      localized and delocalized spins of Au atoms. In particular, the SPAuNCs show
      excellent biocompatibility without the problem of in vivo accumulation and holds
      promising potential as a clinically effective agent for cancer theragnosis.

PMID- 28741690
TI  - Health care resource utilization before and after perampanel initiation among
      patients with epilepsy in the United States.
AB  - OBJECTIVE: The purpose of this study was to evaluate changes in health care
      resource utilization following the initiation of perampanel for the treatment of
      epilepsy in the United States. METHODS: Health care claims from Symphony Health's
      Integrated Dataverse database between December 2012 and November 2015 were
      analyzed. Patients newly initiated on perampanel, having >=1 epilepsy
      (International Classification of Diseases, Ninth Revision, Clinical Modification
      [ICD-9-CM] code 345.xx, ICD-10-CM code G40.xxx) or nonfebrile convulsion (ICD-9
      CM code 780.39, ICD-10-CM code R56.9) diagnosis, and having >=6 months of
      baseline and observation periods were included. Patients <12 years old at
      perampanel initiation were excluded. RESULTS: Of the 2,508 perampanel patients
      included in the study, the mean [median] (+/-standard deviation [SD]) age was
      35.8 [34] (+/-16.0) years and 56.2% were female. The mean [median] (+/-SD)
      observation duration was 459.8 [462] (+/-146.3) days in the postperampanel
      period. The postperampanel period was associated with significantly lower rates
      of all health care resource utilization outcomes than the pre-period. For the
      post- versus pre-period, perampanel users had 42.3 versus 53.8 overall
      hospitalizations per 100 person-years (rate ratio [RR] = 0.80, p < 0.001) and
      1,240.2 versus 1,343.8 outpatient visits per 100 person-years (RR = 0.91, p <
      0.001). Epilepsy-related hospitalizations and outpatient visits were 25.2 versus
      33.6 per 100 person-years (RR = 0.76, p < 0.001) and 327.0 versus 389.0 per 100
      person-years (RR = 0.84, p < 0.001), respectively. Additionally, a significantly
      lower rate of status epilepticus in the post-period (1.8 events per 100 person
      years) was observed compared to the pre-period (4.4 events per 100 person-years;
      RR = 0.43, p < 0.001). The monthly time trend of hospitalizations showed an
      increasing trend leading up to the initiation of perampanel, after which the
      hospitalizations decreased steadily. SIGNIFICANCE: Use of perampanel for the
      treatment of epilepsy was associated with significant reduction in all-cause and
      epilepsy-related health care resource utilization, including hospitalizations,
      especially for status epilepticus, and outpatient visits.

PMID- 28741691
TI  - Earlier initiation of transfusional and iron chelation therapies in recently born
      children with transfusion-dependent thalassemia.

PMID- 28741692
TI  - Inflammatory and endothelial markers during vaso-occlusive crisis and acute chest
      syndrome in sickle cell disease.

PMID- 28741693
TI  - Antioxidants protect proteins' anchorage to the bilayer by improving plasma
      membrane integrity of ram spermatozoa during liquid preservation in a soya
      lecithin-based diluent.
AB  - Antioxidants are known to prevent the reactive oxygen species (ROS)-mediated
      peroxidative damage to the membrane lipids during hypothermic storage of
      mammalian spermatozoa. We hypothesized here that ROS also affect the lipid
      protein interactions, thereby diminishing the membrane's integrity and proteins'
      anchorage to the bilayer. Antioxidants prevent these damages by scavenging the
      ROS. Ejaculates from Patanwadi rams were pooled after subjective evaluation and
      centrifuged using Percoll(r) . Sperm pellet was resuspended in soya lecithin-Tris
      fructose diluent (400 * 106  cells/ml) containing either antioxidants (100 IU/ml
      catalase + 10 mM reduced glutathione) or no antioxidant. Aliquots were chilled to
      5 degrees C in a cabinet and stored in a refrigerator at 3-5 degrees C for 72 hr.
      Sperm motility, viability, lipid peroxidation (LPO) and hypo-osmotic swelling
      test (HOST) were performed at 0, 24, 48 and 72 hr. Sperm proteins extracted with
      0.5% Triton X-100 were resolved by SDS-PAGE and quantified using Quantity One
      software (Bio-Rad, USA). The rapid motility, linearity and straight-line velocity
      (VSL) were found significantly (p < .05) higher in the antioxidant-treated group
      compared to the control at 48 hr of storage. Sperm viability was found comparable
      between the groups. Higher HOST response and lower LPO were found in the
      antioxidant-treated sample compared to the control both at 48 and at 72 hr.
      Overall, the proteins P1 (106.09 kDa), P2 (87.00 kDa) and P4 (51.14 kDa) were
      lower (p < .05) in the sperm extract of antioxidant-treated group compared to the
      control. The content of P4 (51.14 kDa) in sperm extract was found to increase (p
      < .05) earlier (48 vs. 72 hr) in the control group compared to the antioxidant
      treated group. Altogether, the results suggested that antioxidants reduced LPO in
      spermatozoa, resulting in higher sperm motility, plasma membrane integrity and
      protection of proteins' anchorage to the plasma membrane at 48 and 72 hr of
      storage.

PMID- 28741694
TI  - Reduced parahippocampal volume and psychosis symptoms in Alzheimer's disease.
AB  - OBJECTIVE: Establishing structural imaging correlates of psychosis symptoms in
      Alzheimer's disease (AD) could localise pathology and target symptomatic
      treatment. This study investigated whether psychosis symptoms are associated with
      visuoperceptual or frontal networks, and whether regional brain volume
      differences could be linked with the paranoid (persecutory delusions) or
      misidentification (misidentification phenomena and/or hallucinations) subtypes.
      METHODS: A total of 104 patients with probable AD (AddNeuroMed; 47 psychotic, 57
      non-psychotic), followed up for at least one year with structural MRI at
      baseline. Presence and subtype of psychosis symptoms were established using the
      Neuropsychiatric Inventory. Volume and cortical thickness measures in
      visuoperceptual and frontal networks were explored using multivariate analyses to
      compare with both a global (psychotic versus not) and subtype-specific approach,
      adjusting for potential confounding factors. RESULTS: There was a significant
      main effect of psychosis subtypes on the ventral visual stream region of interest
      (F30,264  = 1.65, p = 0.021, np2  = 0.16). This was explained by reduced left
      parahippocampal gyrus volume (F1,97  = 11.1, p = 0.001, np2  = 0.10). When
      comparisons were made across psychosis subtypes, left parahippocampal volume
      reduction remained significant (F7,95  = 3.94, p = 0.011, np2  = 0.11) and was
      greatest for the misidentification and mixed subtypes compared to paranoid and
      non-psychotic groups. CONCLUSIONS: These findings implicate the ventral visual
      stream in psychosis in AD, consistent with integrative theories regarding origins
      of psychosis, and provide further evidence for a role in the misidentification
      subtype. Specifically, reduced volume in the parahippocampal gyrus is implicated
      in misidentification delusion formation, which we hypothesise is due to its role
      in context attribution. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28741695
TI  - Transparent, Flexible, and Conductive 2D Titanium Carbide (MXene) Films with High
      Volumetric Capacitance.
AB  - 2D transition-metal carbides and nitrides, known as MXenes, have displayed
      promising properties in numerous applications, such as energy storage,
      electromagnetic interference shielding, and catalysis. Titanium carbide MXene
      (Ti3 C2 Tx ), in particular, has shown significant energy-storage capability.
      However, previously, only micrometer-thick, nontransparent films were studied.
      Here, highly transparent and conductive Ti3 C2 Tx films and their application as
      transparent, solid-state supercapacitors are reported. Transparent films are
      fabricated via spin-casting of Ti3 C2 Tx nanosheet colloidal solutions, followed
      by vacuum annealing at 200  degrees C. Films with transmittance of 93% (~4 nm)
      and 29% (~88 nm) demonstrate DC conductivity of ~5736 and ~9880 S cm-1 ,
      respectively. Such highly transparent, conductive Ti3 C2 Tx films display
      impressive volumetric capacitance (676 F cm-3 ) combined with fast response.
      Transparent solid-state, asymmetric supercapacitors (72% transmittance) based on
      Ti3 C2 Tx and single-walled carbon nanotube (SWCNT) films are also fabricated.
      These electrodes exhibit high capacitance (1.6 mF cm-2 ) and energy density (0.05
      uW h cm-2 ), and long lifetime (no capacitance decay over 20 000 cycles),
      exceeding that of graphene or SWCNT-based transparent supercapacitor devices.
      Collectively, the Ti3 C2 Tx films are among the state-of-the-art for future
      transparent, conductive, capacitive electrodes, and translate into
      technologically viable devices for next-generation wearable, portable
      electronics.

PMID- 28741696
TI  - Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis
      thaliana.
AB  - The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been
      mainly characterized with regard to their contribution as activators of
      fermentation in plants. However, transcriptional changes measured in conditions
      that stabilize these transcription factors exceed the mere activation of this
      biochemical pathway, implying additional roles performed by the ERF-VIIs in other
      processes. We evaluated gene expression in transgenic Arabidopsis lines
      expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and
      identified genes affected by this transcriptional regulator and its homologs,
      including some involved in oxidative stress response, which are not universally
      induced under anaerobic conditions. The contribution of the ERF-VIIs in
      regulating this set of genes in response to chemically induced or submergence
      stimulated mitochondria malfunctioning was found to depend on the plant
      developmental stage. A similar age-dependent mechanism also restrained ERF-VII
      activity upon the core-hypoxic genes, independently of the N-end rule pathway,
      which is accounted for the control of the anaerobic response. To conclude, this
      study shed new light on a dual role of ERF-VII proteins under submergence: as
      positive regulators of the hypoxic response and as repressors of oxidative-stress
      related genes, depending on the developmental stage at which plants are
      challenged by stress conditions.

PMID- 28741697
TI  - Xenotransplantation literature update, May/June 2017.

PMID- 28741698
TI  - The relationship between vision impairment and well-being among centenarians:
      findings from the Georgia Centenarian Study.
AB  - OBJECTIVE: The current study evaluated the visual function among centenarians and
      assessed the relationship between vision, social support, and well-being.
      METHODS: This study used the data set of the Georgia Centenarian Study including
      106 centenarians (18 men and 88 women). We used scores of the Snellen chart for
      objective vision and self-reports for subjective vision. Social support,
      depression, and loneliness were also assessed. RESULTS: Approximately 75% of the
      centenarians showed some level of objective visual impairment, and 56% of them
      reported that they had visual impairment. Objective vision impairment was
      significantly related to depression. Multiple regression analysis revealed that
      both variables of visual function were significantly associated with depression,
      but not loneliness. In the model including depression, a significant interaction
      was obtained for social support and objective vision. Centenarians reported lower
      level of depression when they had social support. However, centenarians who had
      low level of visual function tended to report higher depression even if they had
      social support. IMPLICATIONS: These results indicated that vision function was
      related to centenarians' well-being, especially depression. Copyright (c) 2017
      John Wiley & Sons, Ltd.

PMID- 28741699
TI  - The flagellar apparatus of the glaucophyte Cyanophora cuspidata.
AB  - Glaucophytes are a kingdom-scale lineage of unicellular algae with uniquely
      underived plastids. The genus Cyanophora is of particular interest because it is
      the only glaucophyte that is a flagellate throughout its life cycle, making its
      morphology more directly comparable than other glaucophytes to other eukaryote
      flagellates. The ultrastructure of Cyanophora has already been studied, primarily
      in the 1960s and 1970s. However, the usefulness of that work has been undermined
      by its own limitations, subsequent misinterpretations, and a recent taxonomic
      revision of the genus. For example, Cyanophora's microtubular roots have been
      widely reported as cruciate, with rotationally symmetrical wide and thin roots,
      although the first ultrastructural work described it as having three wide and one
      narrow root. We examine Cyanophora cuspidata using scanning and transmission
      electron microscopy, and construct a model of its cytoskeleton using serial
      section TEM. We confirm the earlier model, with asymmetric roots. We describe
      previously unknown and unsuspected features of its microtubular roots, including
      (i) a rearrangement of individual microtubules within the posterior right root,
      (ii) a splitting of the posterior left root into two subroots, and (iii) the
      convergence and termination of the narrow roots against wider ones in both the
      anterior and posterior subsystems of the flagellar apparatus. We also describe a
      large complement of nonmicrotubular components of the cytoskeleton, including a
      substantial connective between the posterior right root and the anterior basal
      body. Our work should serve as the starting point for a re-examination of both
      internal glaucophyte diversity and morphological evolution in eukaryotes.

PMID- 28741700
TI  - Financial aspects of organ procurement from deceased donors in the USA-Relevance
      to xenotransplantation.
AB  - When clinical xenotransplantation is introduced, the costs associated with
      acquisition of a genetically engineered pig organ are as yet unknown. How will
      these costs compare with those currently associated with the acquisition of
      deceased human organs? An understanding of the financial aspects of deceased
      organ and tissue procurement in the USA is therefore worthwhile. We have
      therefore attempted to review certain economic aspects of non-profit and for
      profit organizations that provide cadaveric organs and/or tissues for purposes of
      transplantation into patients with end-stage organ failure, cellular
      deficiencies, or in need of reconstructive procedures. We briefly consider the
      laws, organizations, and business practices that govern the acquisition,
      processing, and/or distribution of cadaveric organs and tissues, and the economic
      implications of industry practices. In particular, we explore and highlight what
      we perceive as a lack of transparency and oversight with regard to financial
      practices, and we question whether donor families would be entirely happy with
      the business environment that has developed from their altruistic donations.
      Until xenotransplantation becomes established clinically, which will negate the
      need for any system of organ procurement and allocation, we suggest that those
      involved in organ and cell transplantation, as well as those who participate in
      reconstructive surgery, should take responsibility to ensure that the financial
      practices associated with procurement are transparent, and overseen/regulated by
      a responsible authority. We suggest the major transplant societies should take a
      lead in this respect. The ability to acquire a genetically engineered pig organ
      whenever required through a simple commercial transaction (as in the acquisition
      of a life-saving drug) will be greatly to the patient's benefit.

PMID- 28741701
TI  - Dissecting molecular architecture of post-synaptic density at excitatory
      synapses: An Editorial Highlight for 'Hierarchical organization and genetically
      separable subfamilies of PSD95 postsynaptic supercomplexes' on page 504.
AB  - This Editorial highlights a study by Frank and colleagues (2017) in the current
      issue of Journal of Neurochemistry. The authors report the genetic composition
      and stoichiometry of endogenous subfamilies of PSD95-containing supercomplexes in
      the mouse brain using an innovative strategy of combining gene-tagging knock-in,
      targeted mutations, and quantitative biochemical assays. Their findings shed new
      light on our understanding of the genetic hierarchy required for the assembly of
      distinct supercomplex subfamilies at excitatory synapses in the brain.

PMID- 28741702
TI  - Automatic thoughts as a predictor of internalizing and externalizing problems in
      Chinese adolescents: A test of the cognitive content-specificity hypothesis with
      age effects.
AB  - The main aim of the current study was to test the cognitive content-specificity
      hypothesis across internalizing and externalizing problems in Chinese
      adolescents. The participants consisted of 2,158 adolescents aged 11-19 years
      from three middle schools, and they completed a number of measures assessing a
      wide range of automatic thoughts and syndromes related to internalizing and
      externalizing problems. Multivariate regression analyses demonstrated that
      thoughts about social threats, personal failure and hostility were the strongest
      predictors of anxiety, depression, and externalizing problems, respectively. Age
      was a statistically significant, albeit modest, moderator of the relationship
      between automatic thoughts about social threat and anxiety. The current study
      provides support for the cognitive content-specificity hypothesis in
      internalizing and externalizing problems in a Chinese sample.

PMID- 28741703
TI  - Intravesical bacillus Calmette-Guerin instillation in non-muscle-invasive bladder
      cancer: A review.
AB  - Intravesical bacillus Calmette-Guerin has been the standard of care for high-risk
      non-muscle-invasive bladder cancer for 40 years. It remains one of the most
      successful immunotherapies ever used. Bacillus Calmette-Guerin shows superior
      efficacy to alternative intravesical treatments, and has an established role in
      reducing both recurrence and progression in non-muscle-invasive bladder cancer.
      It remains relatively safe, and has acceptable tolerability of both local and
      systemic side-effects. The present review provides insights into the role of
      bacillus Calmette-Guerin compared with alternative treatments both in primary and
      refractory settings.

PMID- 28741704
TI  - Methylation of protein phosphatase 2A-Influence of regulators and environmental
      stress factors.
AB  - Protein phosphatase 2A catalytic subunit (PP2A-C) has a terminal leucine
      subjected to methylation, a regulatory mechanism conserved from yeast to mammals
      and plants. Two enzymes, LCMT1 and PME1, methylate and demethylate PP2A-C,
      respectively. The physiological importance of these posttranslational
      modifications is still enigmatic. We investigated these processes in Arabidopsis
      thaliana by mutant phenotyping, by global expression analysis, and by monitoring
      methylation status of PP2A-C under different environmental conditions. The lcmt1
      mutant, possessing essentially only unmethylated PP2A-C, had less dense rosettes,
      and earlier flowering than wild type (WT). The pme1 mutant, with 30% reduction in
      unmethylated PP2A-C, was phenotypically comparable with WT. Approximately 200
      overlapping genes were twofold upregulated, and 200 overlapping genes were
      twofold downregulated in both lcmt1 and pme1 relative to WT. Differences between
      the 2 mutants were also striking; 97 genes were twofold upregulated in pme1
      compared with lcmt1, indicating that PME1 acts as a negative regulator for these
      genes. Analysis of enriched GO terms revealed categories of both abiotic and
      biotic stress genes. Furthermore, methylation status of PP2A-C was influenced by
      environmental stress, especially by hypoxia and salt stress, which led to
      increased levels of unmethylated PP2A-C, and highlights the importance of PP2A-C
      methylation/demethylation in environmental responses.

PMID- 28741705
TI  - House dust mites as potential carriers for IgE sensitization to bacterial
      antigens.
AB  - BACKGROUND: IgE reactivity to antigens from Gram-positive and Gram-negative
      bacteria is common in patients suffering from respiratory and skin manifestations
      of allergy, but the routes and mechanisms of sensitization are not fully
      understood. The analysis of the genome, transcriptome and microbiome of house
      dust mites (HDM) has shown that Staphylococcus aureus (S. aureus) and Escherichia
      coli (E. coli) species are abundant bacteria within the HDM microbiome.
      Therefore, our aim was to investigate whether HDM are carriers of bacterial
      antigens leading to IgE sensitization in patients suffering from atopic
      dermatitis. METHODS: Plasma samples from patients with AD (n = 179) were analysed
      for IgE reactivity to a comprehensive panel of microarrayed HDM allergen
      molecules and to S. aureus and E. coli by IgE immunoblotting. Antibodies specific
      for S. aureus and E. coli antigens were tested for reactivity to nitrocellulose
      blotted extract from purified HDM bodies, and the IgE-reactive antigens were
      detected by IgE immunoblot inhibition experiments. IgE antibodies directed to
      bacterial antigens in HDM were quantified by IgE ImmunoCAPTM inhibition
      experiments. RESULTS: IgE reactivity to bacterial antigens was significantly more
      frequent in patients with AD sensitized to HDM than in AD patients without HDM
      sensitization. S. aureus and E. coli antigens were detected in immune-blotted HDM
      extract, and the presence of IgE-reactive antigens in HDM was demonstrated by
      qualitative and quantitative IgE inhibition experiments. CONCLUSION: House dust
      mites (HDM) may serve as carriers of bacteria responsible for the induction of
      IgE sensitization to microbial antigens.

PMID- 28741706
TI  - A Strategy to Produce High Efficiency, High Stability Perovskite Solar Cells
      Using Functionalized Ionic Liquid-Dopants.
AB  - Functionalized imidazolium iodide salts (ionic liquids) modified with ?CH2
      ?CH?CH2 , ?CH2 C?CH, or ?CH2 C?N groups are applied as dopants in the synthesis
      of CH3 NH3 PbI3 -type perovskites together with a fumigation step. Notably, a
      solar cell device prepared from the perovskite film doped with the salt
      containing the ?CH2 ?CH?CH2 side-chain has a power conversion efficiency of
      19.21%, which is the highest efficiency reported for perovskite solar cells
      involving a fumigation step. However, doping with the imidazolium salts with the
      ?CH2 C?CH and ?CH2 C?N groups result in perovskite layers that lead to solar cell
      devices with similar or lower power conversion efficiencies than the dopant-free
      cell.

PMID- 28741707
TI  - Photophysical and Photochemical Properties of Naturally Occurring normelinonine F
      and Melinonine F Alkaloids and Structurally Related N(2)- and/or N(9)-methyl-beta
      carboline Derivatives.
AB  - In the present work, we have synthesized and fully characterized the
      photophysical and photochemical properties of a selected group of N-methyl-beta
      carboline derivatives (9-methyl-beta-carbolines and iodine salts of 2-methyl- and
      2,9-dimethyl-beta-carbolinium) in aqueous solutions, in the pH range 4.0-14.5.
      Moreover, despite the quite extensive studies reported in the literature
      regarding the overall photophysical behavior of N-unsubstituted betaCs, this work
      constitutes the first full and unambiguous characterization of anionic species of
      N-unsubstituted betaCs (norharmane, harmane and harmine), present in aqueous
      solution under highly alkaline conditions (pH > 13.0). Acid dissociation
      constants (Ka ), thermal stabilities, room temperature UV-visible absorption and
      fluorescence emission and excitation spectra, fluorescence quantum yields (FF )
      and fluorescence lifetimes (tauF ), as well as quantum yields of singlet oxygen
      production (FDelta ) have been measured for all the studied compounds.
      Furthermore, for the first time to our knowledge, chemometric techniques (MCR-ALS
      and PARAFAC) were applied on these systems, providing relevant information about
      the equilibria and species involved. The impact of all the foregoing observations
      on the biological role, as well as the potential biotechnological applications of
      these compounds, is discussed.

PMID- 28741708
TI  - Hollow MXene Spheres and 3D Macroporous MXene Frameworks for Na-Ion Storage.
AB  - 2D transition metal carbides and nitrides, named MXenes, are attracting
      increasing attentions and showing competitive performance in energy storage
      devices including electrochemical capacitors, lithium- and sodium-ion batteries,
      and lithium-sulfur batteries. However, similar to other 2D materials, MXene
      nanosheets are inclined to stack together, limiting the device performance. In
      order to fully utilize MXenes' electrochemical energy storage capability, here,
      processing of 2D MXene flakes into hollow spheres and 3D architectures via a
      template method is reported. The MXene hollow spheres are stable and can be
      easily dispersed in solvents such as water and ethanol, demonstrating their
      potential applications in environmental and biomedical fields as well. The 3D
      macroporous MXene films are free-standing, flexible, and highly conductive due to
      good contacts between spheres and metallic conductivity of MXenes. When used as
      anodes for sodium-ion storage, these 3D MXene films exhibit much improved
      performances compared to multilayer MXenes and MXene/carbon nanotube hybrid
      architectures in terms of capacity, rate capability, and cycling stability. This
      work demonstrates the importance of MXene electrode architecture on the
      electrochemical performance and can guide future work on designing high
      performance MXene-based materials for energy storage, catalysis, environmental,
      and biomedical applications.

PMID- 28741709
TI  - Prenatal diagnosis of dural sinus malformation in fetus presenting with edema.

PMID- 28741710
TI  - IL-33-expanded human Vgamma9Vdelta2 T cells have anti-lymphoma effect in a mouse
      tumor model.
AB  - From several years, the anticancer effects of Vgamma9 T lymphocytes make these
      cells good candidates for cancer immunotherapies. However, the proved efficacy of
      gammadelta Tau cell-based cancer immunotherapies in some clinical trials was
      minimized due to the inherent toxicity of IL-2, which is essential for the
      combination therapy with Phosphoantigen (PAg). Recently, we showed that IL-33, a
      gamma chain receptor-independent cytokine, was able to induce the in vitro
      proliferation of PAg-activated Vgamma9 T cells, which were fully functional
      expressing IFN-gamma and TNF-alpha and showing in vitro anti-tumor cytotoxicity.
      We proposed IL-33 as an alternative to IL-2 for Vgamma9 T cell-based cancer
      immunotherapies, and have therefore evaluated the efficacy of this cytokine in
      preclinical investigations. This study shows that human Vgamma9 T cells are able
      to proliferate in a mouse model with the combination of PAg and rhIL-33, and that
      IL-33-expanded Vgamma9 T cells can prevent tumor growth in a mouse lymphoma
      model.

PMID- 28741711
TI  - Diffusion tensor imaging in multiple sclerosis at different final outcomes.
AB  - OBJECTIVES: Methods to evaluate the relative contributions of demyelination vs
      axonal degeneration over the long-term course of MS are urgently needed. We used
      magnetic resonance diffusion tensor imaging (DTI) to estimate degrees of
      demyelination and axonal degeneration in the corpus callosum (CC) in cases of MS
      with different final outcomes. MATERIALS AND METHODS: We determined DTI measures
      mean diffusivity (MD), fractional anisotropy (FA), and axial (AD) and radial (RD)
      diffusivities in the CC of 31 MS patients, of whom 13 presented a secondary
      progressive course, 11 a non-progressive course, and seven a monophasic course.
      The study participants were survivors from an incidence cohort of 254 attack
      onset MS patients with 50 years of longitudinal follow-up. As reference, we
      included five healthy individuals without significant morbidity. RESULTS: In
      patients with secondary progression, compared to all other groups, the corpus
      callosum showed increased RD and reduced FA, but no change in AD. None of the
      parameters exhibited differences among non-progressive and monophasic course
      groups and controls. CONCLUSION: Increased RD was observed in secondary
      progressive MS, indicating significant myelin loss. Normal RD values observed in
      the clinically isolated syndrome and non-progressive groups confirm their benign
      nature. AD was not a characterizing parameter for long-term outcome.
      Demyelination revealed by increased RD is a distinguishing trait for secondary
      progression.

PMID- 28741712
TI  - A Series of Linear {FeIII2 FeII } Complexes with Paramagnetic Building-Block
      Modified Spin Crossover Behaviors.
AB  - Tuning of the spin crossover (SCO) behavior through paramagnetic building blocks
      with different steric hindrance effects is of great interest in terms of the
      synergy between SCO and magnetic interactions. Herein, the steric effect of
      specified FeIII building blocks is modified, from the large Tp* (hydridotris(3,5
      dimethylpyrazol-1-yl)borate) analogue to a small Tp (hydrotris(pyrazolyl)borate)
      derivative; the FeII SCO unit and FeIII paramagnetic ions are incorporated into
      three well isolated trinuclear complexes featuring thermally induced and light
      induced SCO properties. Reanalysis of the structures reveals that pi-pi stacking
      interactions play a key role in the thermal hysteresis and anomalous octahedral
      distortion parameter Sigma around the FeII ion. The Tp* ligand showing the
      largest steric hindrance induces elongated FeII -N bond lengths and bending of
      the C=N-FeII angle in 1, as well as having a relatively large electron donor
      effect, which leads to the lowest thermal transition temperature among the three
      compounds.

PMID- 28741713
TI  - Two-colour chewing gum mixing ability test for evaluating masticatory performance
      in children with mixed dentition: validity and reliability study.
AB  - The unappealing taste of the chewing material and the time-consuming repetitive
      task in masticatory performance tests using artificial foodstuff may discourage
      children from performing natural chewing movements. Therefore, the aim was to
      determine the validity and reliability of a two-colour chewing gum mixing ability
      test for masticatory performance (MP) assessment in mixed dentition children.
      Masticatory performance was tested in two groups: systemically healthy fully
      dentate young adults and children in mixed dentition. Median particle size was
      assessed using a comminution test, and a two-colour chewing gum mixing ability
      test was applied for MP analysis. Validity was tested with Pearson correlation,
      and reliability was tested with intra-class correlation coefficient, Pearson
      correlation and Bland-Altman plots. Both comminution and two-colour chewing gum
      mixing ability tests revealed statistically significant MP differences between
      children (n = 25) and adults (n = 27, both P < 0.01). Pearson correlation between
      comminution and two-colour chewing gum mixing ability tests was positive and
      significant (r = 0.418, P = 0.002). Correlations for interobserver reliability
      and test-retest values were significant (r = 0.990, P = 0.0001 and r = 0.995, P =
      0.0001). Although both methods could discriminate MP differences, the comminution
      test detected these differences generally in a wider range compared to two-colour
      chewing gum mixing ability test. However, considering the high reliability of the
      results, the two-colour chewing gum mixing ability test can be used to assess
      masticatory performance in children, especially at non-clinical settings.

PMID- 28741714
TI  - Abnormal fronto-parietal white matter organisation in the superior longitudinal
      fasciculus branches in autism spectrum disorders.
AB  - Core features of autism spectrum disorder (ASD) may be underpinned by disrupted
      functional and structural neural connectivity. Abnormal fronto-parietal
      functional connectivity has been widely reported in the literature; this may be
      underpinned by disrupted microstructural organisation of white matter. The
      superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter
      tract, the structure of which has been little studied in ASD. The fronto-parietal
      projections of this tract (SLF I, II and III) are thought to play an important
      role in a number of cognitive functions including attention and visuospatial
      processing. To date, the isolation of the fronto-parietal branches of the SLF has
      been hampered by limitations of traditional tractography approaches. Constrained
      spherical deconvolution (CSD)-based tractography is an advanced approach that
      allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI
      data were acquired from 45 participants with ASD and 45 age- and IQ-matched
      controls. The SLF I, II and III branches were isolated using CSD-based
      tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was
      observed in the right SLF II relative to controls. The ASD group also showed
      greater linear diffusion coefficient in the left SLF I and the right SLF II. In
      the SLF II, the ASD group had significantly greater right lateralisation of FA in
      comparison with the control group. The clinical and functional implications of
      increased FA in white matter are poorly understood; however, it is possible that
      this increased white matter organisation in the SLF in ASD may contribute to
      relative processing advantages in the condition.

PMID- 28741715
TI  - First report of carglumic acid in a patient with citrullinemia type 1
      (argininosuccinate synthetase deficiency).
AB  - WHAT IS KNOWN AND OBJECTIVE: Carglumic acid is a structural analogue of human N
      acetylglutamate, which has become an alternative therapeutic option for
      hyperammonaemia in organic acidaemias such as isovaleric acidaemia, methylmalonic
      acidaemia and propionic acidaemia, and it has been suggested in other urea cycle
      disorders such as ornithine transcarbamylase deficiency and carbamoyl phosphate
      synthetase 1 deficiency. CASE DESCRIPTION: A male newborn was diagnosed with
      citrullinemia after serum amino acid analyses revealed markedly elevated
      citrulline concentration together with homozygous p.Gly390Arg mutation in ASS1
      gene. The ammonia concentration decreased and blood gas analysis normalized after
      peritoneal dialysis was performed for three days. Also, sodium benzoate, L
      arginine and parenteral nutrition with glucose and lipid therapy were initiated.
      Until 1 year of age, low adherence to sodium benzoate therapy due to unpleasant
      taste caused hyperammonaemic episodes and obligated us to initiate carglumic acid
      (100 mg/kg/day) therapy. During treatment with carglumic acid, the median ammonia
      level was 45.6 umol/L. The patient's treatment was switched from carglumic acid
      to sodium phenylbutyrate when he was 4.5 years old. Currently, the patient is 6.5
      years old and remains under follow-up with sodium phenylbutyrate, L-arginine and
      protein-restricted diet. Plasma ornithine level was found to be significantly
      lower during the carglumic acid treatment compared to other treatments (P=.039).
      Also, glutamic acid was found to be higher during the sodium benzoate treatment
      period compared to other treatment periods (P=.024). WHAT IS NEW AND CONCLUSION:
      To the best of our knowledge, this is the first report describing the long-term
      use of carglumic acid in a patient with argininosuccinate synthetase deficiency.

PMID- 28741717
TI  - Erratum.

PMID- 28741716
TI  - Influence of lateral position and pneumoperitoneum on oropharyngeal leak pressure
      with two types of laryngeal mask airways.
AB  - BACKGROUND: An important parameter to monitor adequate ventilation for laryngeal
      mask airway (LMA) is its oropharyngeal leak pressure (OLP). This study was
      designed to evaluate and compare the effect of lateral position and
      pneumoperitoneum on the OLP and ventilation efficiency between LMATM Proseal
      (PLMA) and LMATM Supreme (SLMA). METHODS: Patients were randomized to receive
      either the PLMA or the SMLA. The OLP was assessed in both the supine position and
      the lateral position with or without pneumoperitoneum. Minute ventilation was
      increased to maintain normal EtCO2 as far as possible. Ventilatory efficiency was
      scored as Class I (optimal, EtCO2 35-45 mmHg), Class II (suboptimal, EtCO2 45-55
      mmHg) and Class III (poor, EtCO2 >55 mmHg). Adverse events associated with LMA
      such as blood staining on the mask and sore throat were also recorded. RESULTS:
      Within each group, the OLP was higher in the supine position than that in the
      lateral position with or without pneumoperitoneum (P < 0.01). However,
      pneumoperitoneum did not further decrease the OLP. The OLP with PLMA was higher
      compared with SLMA regardless of the position and pneumoperitoneum (P < 0.05 or
      0.01). There was no significant difference in the number of patients in Class
      I/II/III for ventilation scores in the lateral position with pneumoperitoneum
      (83/7/2 in PLMA group and 76/14/2 in SLMA group, respectively). The incidence of
      adverse events was comparable in both groups. CONCLUSION: Our data demonstrate
      that the PLMA has a higher OLP in comparison with the SLMA in the lateral
      position for laparoscopic surgery. Both devices provide comparably adequate
      ventilatory efficiency.

PMID- 28741718
TI  - Plasmapheresis may improve clinical condition in sickle cell disease through its
      effects on red blood cell rheology.

PMID- 28741719
TI  - Involvement of Arabidopsis glutaredoxin S14 in the maintenance of chlorophyll
      content.
AB  - Plant class-II glutaredoxins (GRXs) are oxidoreductases carrying a CGFS active
      site signature and are able to bind iron-sulfur clusters in vitro. In order to
      explore the physiological functions of the 2 plastidial class-II isoforms, GRXS14
      and GRXS16, we generated knockdown and overexpression Arabidopsis thaliana lines
      and characterized their phenotypes using physiological and biochemical
      approaches. Plants deficient in one GRX did not display any growth defect,
      whereas the growth of plants lacking both was slowed. Plants overexpressing
      GRXS14 exhibited reduced chlorophyll content in control, high-light, and high
      salt conditions. However, when exposed to prolonged darkness, plants lacking
      GRXS14 showed accelerated chlorophyll loss compared to wild-type and
      overexpression lines. We observed that the GRXS14 abundance and the proportion of
      reduced form were modified in wild type upon darkness and high salt. The dark
      treatment also resulted in decreased abundance of proteins involved in the
      maturation of iron-sulfur proteins. We propose that the phenotype of GRXS14
      modified lines results from its participation in the control of chlorophyll
      content in relation with light and osmotic conditions, possibly through a dual
      action in regulating the redox status of biosynthetic enzymes and contributing to
      the biogenesis of iron-sulfur clusters, which are essential cofactors in
      chlorophyll metabolism.

PMID- 28741720
TI  - Alteplase for Acute Ischemic Stroke after Heparin Reversal with Protamine: A Case
      Report and Review.
AB  - Few patients presenting with acute ischemic stroke (AIS) are eligible for
      alteplase, especially those receiving ongoing anticoagulation. We describe the
      first reported case of a patient receiving full-dose intravenous (IV) alteplase
      for AIS after heparin reversal with protamine. A 73-year-old man presented with
      AIS. He was treated with IV heparin, tirofiban, loading-dose prasugrel, and
      aspirin before percutaneous coronary intervention (PCI) for placement of a right
      coronary artery stent. One hour following PCI, he abruptly developed left
      hemiparesis and dysphagia. The National Institutes of Health Stroke Scale was 12,
      and activated partial thromboplastin time (aPTT) was longer than 150 seconds.
      Head computed tomography (CT) showed no acute pathology, and CT angiogram showed
      no large-vessel occlusion amenable to mechanical thrombectomy. Repeat aPTT,
      obtained 45 minutes later, was 110 seconds, at which time protamine 40 mg IV was
      administered. At 144 minutes from last known well time, full-dose IV alteplase
      (0.9 mg/kg) was administered. Follow-up head imaging at 25 hours showed right
      pontine and cerebellar AIS with no evidence of hemorrhage. The patient was
      discharged to inpatient rehabilitation 2 days later. Modified Rankin Scale at 3
      months was 3, improved from 5 at discharge. Given the lack of adverse events
      associated with IV alteplase in our patient, we advocate cautious evaluation for
      potential reversal of acutely administered anticoagulation to facilitate
      alteplase administration in severely disabled patients who are not eligible for
      mechanical intervention and would have been excluded from definitive AIS
      treatment.

PMID- 28741721
TI  - Left Ventricular Septal Hypertrophy in Elderly Patients With Aortic Stenosis.
AB  - OBJECTIVES: Left ventricular (LV) septal hypertrophy in aortic stenosis raises
      diagnostic and therapeutic questions. However, the etiology and clinical
      consequences of this finding have not been well studied. The aim of this study
      was to perform a morphologic evaluation of the LV in aortic stenosis and to
      investigate the contributing factors and consequences of septal hypertrophy.
      METHODS: Patients with moderate or severe aortic stenosis were prospectively
      enrolled. Patients with previous myocardial infarction, wall motion
      abnormalities, at least moderate valvular regurgitation, known cardiomyopathy, an
      LV ejection fraction of less than 50%, and age younger than 65 years were
      excluded. RESULTS: Forty-one patients underwent a final analysis. Septal
      hypertrophy (LV septal wall thickness >=15 mm) was confirmed in 21 of 41
      patients. The septal hypertrophy group had higher peak aortic valve velocity, a
      higher diabetes mellitus rate, and a higher rate and longer duration of
      hypertension than those without septal hypertrophy. The peak aortic valve
      velocity (odds ratio, 7.1; 95% confidence interval, 1.4-37.1) and diabetes
      mellitus (odds ratio, 7.4; 95% confidence interval, 1.2-46.2) were the
      significant factors associated with septal hypertrophy by multivariate analysis.
      Intraventricular conduction disturbance on electrocardiography was more frequent
      in the septal hypertrophy group (P = .021). CONCLUSIONS: Left ventricular septal
      hypertrophy was commonly observed in elderly patients with aortic stenosis, and a
      higher aortic valve velocity, hypertension, and diabetes mellitus were associated
      factors. Intraventricular conduction disturbance occurred more often in patients
      with septal hypertrophy than those without, which implies the pathophysiologic
      consequence. Further studies are needed to determine the impact of septal
      hypertrophy and intraventricular conduction disturbance on the prognosis of
      patients after aortic valve interventions.

PMID- 28741722
TI  - The intriguing role of VEGF in varicocele.

PMID- 28741723
TI  - Analysis of the incidence and factors predictive of outcome in patients with head
      and neck cancer with pulmonary nodules.
AB  - BACKGROUND: The management of pulmonary nodules is challenging; unfortunately,
      little is known about the incidence and significance of pulmonary nodules in
      patients with head and neck cancer. METHODS: A review was conducted of 400
      consecutive patients with head and neck cancer. Imaging was reviewed to identify
      the incidence of nodules and patient, tumor, and radiological factors associated
      with the risk of malignancy. RESULTS: Nodules were found in 58% of patients, with
      a malignant rate of 6%. Age was the only predictor of having a nodule and
      advanced-stage III + IV was a predictor of malignancy (P = .023; odds ratio [OR]
      10.64; confidence interval 1.33-84.98). CONCLUSION: Patients presenting with head
      and neck cancer have a higher incidence of pulmonary nodules and a higher risk of
      malignancy. In contrast to the British Thoracic Society (BTS) guidelines, which
      use size to guide the need for serial scans, we would recommend follow-up imaging
      in all patients with head and neck cancer with nodules, irrespective of size.

PMID- 28741724
TI  - Quantitative comparison of the histological subtypes of seborrheic keratosis
      using computer-aided image analysis.

PMID- 28741725
TI  - Cell-derived micro-environment helps dental pulp stem cells promote dental pulp
      regeneration.
AB  - OBJECTIVES: The function of the dental pulp is closely connected to the
      extracellular matrix (ECM) structure, and ECM has received significant attention
      due to its biological functions for regulating cells. As such, the interaction
      between the ECM niche and cells is worth exploring for potential clinical uses.
      MATERIALS AND METHODS: In this study, dental pulp stem cell (DPSC)-derived ECM
      (DPM) was prepared through cell culture and decellularization to function as the
      cell niche, and changes in DPSC behaviour and histological analysis of dental
      pulp tissue regeneration were evaluated following the DPM culture. DPM promoted
      the replication of DPSCs and exhibited retention of their mineralization. Then,
      the DPM-based culture strategy under odontogenic culture medium was further
      investigated, and the mineralization-related markers showed that DPSCs were
      regulated towards odontogenic differentiation. Dental pulp-like tissue with well
      arranged ECM was harvested after a 2-month subcutaneous implantation in nude mice
      with DPM application. Additionally, DPSCs cultured on the plastic culture surface
      showed the up-regulation of mineralization makers in vitro, but there was a
      disorder in matrix formation and mineralization when the cells were cultured in
      vivo. RESULTS AND CONCLUSIONS: DPM-based cultivation could serve as a cell niche
      and modulate DPSC behaviour, and this method also provided an alternative to
      harvest tissue-specific ECM and provided a strategy for ECM-cell interaction.

PMID- 28741726
TI  - NS1643 enhances ionic currents in a G604S-WT hERG co-expression system associated
      with long QT syndrome 2.
AB  - Loss of function mutations in the human ether-a-go-go-related gene (hERG) cause
      long QT syndrome type 2 (LQT2). Most LQT2 patients are heterozygous mutation
      carriers in which the mutant hERG exerts potent dominant-negative effects. 1, 3
      bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) is known to enhance IKr in
      WT-hERG. We investigated its actions following lipofectamine-induced expression
      of both mutant G604S- and WT-hERG in the heterologous HEK293 expression system.
      Cells transfected with pcDNA3-G604S-hERG did not lead to any expression of
      detectable currents whether before or following NS1643 challenge. Cells
      transfected with both pcDNA3-WT-hERG and pcDNA3-G604S-hERG showed reduced hERG
      currents compared to those transfected with pcDNA3-G604S-hERG consistent with the
      reduced trafficking and formation of modified heteromeric WT-G604S channels
      reported on earlier occasions. Nevertheless, NS1643 then continued to produce
      concentration- and voltage-dependent increases in hERG current amplitude. It did
      not affect the voltage dependence of activation, recovery from inactivation and
      deactivation. However, NS1643 (30 MUmol/L) slowed steady state inactivation and
      shifted the steady state half maximal activation voltage (V1/2 ) of the
      inactivation curve by +10 mV, and significantly increased the time constants of
      inactivation. Our present experimental results suggest that NS1643 significantly
      increases ion current and attenuates its inactivation in cells co-expressing
      G604S-hERG and WT-hERG. These findings raise the possibility that hERG channel
      activators offer potential treatment strategies for inherited LQT2.

PMID- 28741727
TI  - Placental pericytes and cytomegalovirus infectivity: Implications for HCMV
      placental pathology and congenital disease.
AB  - PROBLEM: Placental pericytes are essential for placental microvascular function,
      stability, and integrity. Mechanisms of human cytomegalovirus (HCMV) pathogenesis
      incorporating placental pericytes are unknown. METHOD OF STUDY: HCMV-infected
      placental tissue was stained by dual-labeled immunohistochemistry. Primary
      placental pericytes, cytotrophoblasts, and villous fibroblasts were exposed to
      HCMV; and infectivity was analyzed by microscopy and immunofluorescence. Cytokine
      expression was examined by Luminex assay. A HCMV-GFP recombinant virus was used
      to examine replication kinetics. RESULTS: Immunohistochemistry showed HCMV in
      trophoblast and the villous core with T-cell and macrophage infiltration. Primary
      HCMV isolate from a patient (SBCMV)- infected pericytes showed dysregulation of
      proinflammatory and angiogenic cytokines when compared to control cells. A tri
      cell model of the villous floor showed a unique expression profile. Finally, we
      show pericytes infected in vivo with HCMV in placental tissue from a congenitally
      infected child. CONCLUSION: Placental pericytes support HCMV replication,
      inducing proinflammatory and angiogenic cytokines that likely contribute to viral
      dissemination, placenta inflammation, and dysregulation of placental
      angiogenesis.

PMID- 28741728
TI  - EBI2 contributes to the induction of thymic central tolerance in mice by
      promoting rapid motility of medullary thymocytes.
AB  - Maturing thymocytes enter the thymic medulla, where they encounter numerous self
      antigens presented by antigen presenting cells (APCs). Those thymocytes that are
      strongly self-reactive undergo either negative selection or diversion into the
      regulatory T-cell lineage. Although the majority of the proteome is expressed in
      the medulla, many self-antigens are expressed by only a minor fraction of
      medullary APCs; thus, thymocytes must efficiently enter the medulla and scan APCs
      to ensure central tolerance. Chemokine receptors promote lymphocyte migration,
      organization within tissues, and interactions with APCs in lymphoid organs. The
      chemokine receptor EBI2 governs localization of T cells, B cells, and dendritic
      cells (DCs) during immune responses in secondary lymphoid organs. However, the
      role of EBI2 in thymocyte development has not been elucidated. Here, we
      demonstrate that EBI2 is expressed by murine CD4+ single positive (CD4SP)
      thymocytes and thymic DCs. EBI2 deficiency alters the TCR repertoire, but does
      not grossly impact thymocyte cellularity or subset distribution. EBI2 deficiency
      also impairs negative selection of OT-II TCR transgenic thymocytes responding to
      an endogenous self-antigen. Two-photon imaging revealed that EBI2 deficiency
      results in reduced migration and impaired medullary accumulation of CD4SP
      thymocytes. These data identify a role for EBI2 in promoting efficient thymic
      central tolerance.

PMID- 28741729
TI  - Influence of timing of delayed hard palate closure on articulation skills in 3
      year-old Danish children with unilateral cleft lip and palate.
AB  - BACKGROUND: Differing results regarding articulation skills in young children
      with cleft palate (CP) have been reported and often interpreted as a consequence
      of different surgical protocols. AIMS: To assess the influence of different
      timing of hard palate closure in a two-stage procedure on articulation skills in
      3-year-olds born with unilateral cleft lip and palate (UCLP). Secondary aims were
      to compare results with peers without CP, and to investigate if there are gender
      differences in articulation skills. Furthermore, burden of treatment was to be
      estimated in terms of secondary surgery, hearing and speech therapy. METHODS &
      PROCEDURES: A randomized controlled trial (RCT). Early hard palate closure (EHPC)
      at 12 months versus late hard palate closure (LHPC) at 36 months in a two-stage
      procedure was tested in a cohort of 126 Danish-speaking children born with non
      syndromic UCLP. All participants had the lip and soft palate closed around 4
      months of age. Audio and video recordings of a naming test were available from
      113 children (32 girls and 81 boys) and were transcribed phonetically. Recordings
      were obtained prior to hard palate closure in the LHPC group. The main outcome
      measures were percentage consonants correct adjusted (PCC-A) and consonant errors
      from blinded assessments. Results from 36 Danish-speaking children without CP
      obtained previously by Willadsen in 2012 were used for comparison. OUTCOMES &
      RESULTS: Children with EHPC produced significantly more target consonants
      correctly (83%) than children with LHPC (48%; p < .001). In addition, children
      with LHPC produced significantly more active cleft speech characteristics than
      children with EHPC (p < .001). Boys achieved significantly lower PCC-A scores
      than girls (p = .04) and produced significantly more consonant errors than girls
      (p = .02). No significant differences were found between groups regarding burden
      of treatment. The control group performed significantly better than the EHPC and
      LHPC groups on all compared variables.

PMID- 28741730
TI  - Fermentation quality and nutritive value of total mixed ration silages based on
      desert wormwood (Artemisia desertorum Spreng.) combining with early stage corn.
AB  - This study aimed to investigate the fermentation quality and nutritive value of
      total mixed ration (TMR) silages based on desert wormwood (DW) combined with
      early stage corn (ESC) as forage and determine an optimum formula. Desert
      wormwood and ESC were harvested, chopped, and mixed with other ingredients
      according to a formula, packed into laboratory silos at densities of 500-550 g/L,
      and stored in the dark for 60 days. The DW proportions in the forage of TMR were
      1, 0.75, 0.50, 0.25 and 0, based on fresh weight. As the proportion of DW
      decreased, the pH also decreased (P < 0.05), while lactic acid, lactic
      acid/acetic acid, crude protein, starch, and the in vitro digestibility of dry
      matter and neutral detergent fiber increased (P < 0.05). Ammonia nitrogen/total
      nitrogen in the TMR silages with DW proportions of 0.75, 0.25 and 0 in the forage
      was more than 10%. These results indicated that the quality of the TMR silage
      containing DW alone as forage was poor, TMR silages containing DW proportions of
      0.75 and 0.25, and ESC alone, in the forage were not well preserved. The optimum
      TMR silage formula contained a DW proportion of 0.5 in the forage.

PMID- 28741731
TI  - The evolutionary history of the DMRT3 'Gait keeper' haplotype.
AB  - A previous study revealed a strong association between the DMRT3:Ser301STOP
      mutation in horses and alternate gaits as well as performance in harness racing.
      Several follow-up studies have confirmed a high frequency of the mutation in
      gaited horse breeds and an effect on gait quality. The aim of this study was to
      determine when and where the mutation arose, to identify additional potential
      causal mutations and to determine the coalescence time for contemporary
      haplotypes carrying the stop mutation. We utilized sequences from 89 horses
      representing 26 breeds to identify 102 SNPs encompassing the DMRT3 gene that are
      in strong linkage disequilibrium with the stop mutation. These 102 SNPs were
      genotyped in an additional 382 horses representing 72 breeds, and we identified
      14 unique haplotypes. The results provided conclusive evidence that
      DMRT3:Ser301STOP is causal, as no other sequence polymorphisms showed an equally
      strong association to locomotion traits. The low sequence diversity among mutant
      chromosomes demonstrated that they must have diverged from a common ancestral
      sequence within the last 10 000 years. Thus, the mutation occurred either just
      before domestication or more likely some time after domestication and then spread
      across the world as a result of selection on locomotion traits.

PMID- 28741732
TI  - Lung Cancer: Short-Term Reproducibility of Intravoxel Incoherent Motion
      Parameters and Apparent Diffusion Coefficient at 3T.
AB  - PURPOSE: To prospectively evaluate the short-term reproducibility of intravoxel
      incoherent motion (IVIM) parameters and apparent diffusion coefficient (ADC) in
      lung cancer patients. MATERIALS AND METHODS: In all, 50 patients (50 lesions)
      underwent free-breathing diffusion-weighted imaging (DWI) (b = 0, 300, 800 s/mm2
      ) and IVIM (10 b-values, 0-1000 s/mm2 ) scans twice (0.5-1-hour interval) at 3T.
      Regions of interests (ROIs) were drawn on ADC maps and IVIM images to derive the
      mean ADC value and IVIM parameters D, D*, and f. Intra- and interobserver, test
      retest reproducibility were assessed with intraclass correlation coefficients
      (ICCs), within coefficient-of-variations (WCVs), and Bland-Altman analysis. The
      effects of type, size, and location of lung lesions were compared with WCVs.
      RESULTS: D and ADC showed good intraobserver reproducibility and interobserver
      agreement, while D* and f showed relatively larger variability (WCV 20.89
      34.97%). The test-retest reproducibility of D and ADC were good (ICC 0.763-0.837;
      WCV 11.12-12.55%), while those of D* and f were relatively poor (ICC 0.604-0.842;
      WCV 36.54-72.62%). D and ADC had decreased reproducibility for lesions <2 cm (WCV
      14.20%, 16.34%, respectively) and for lesions in the lower lung zones (WCV
      16.52%, 14.78%, respectively). f had decreased reproducibility in central lung
      cancers (WCV 50.11%) and lesions >2 cm (WCV 42.64%). D* had even worse
      reproducibility in peripheral lung cancers (WCV 84.11%) and lesions in the lower
      lung zones (WCV 80.84%). CONCLUSION: If the change in ADC, D, D*, and f values is
      less than ~31%, 34%, 170%, and 130%, respectively, it may be caused by
      measurement error. The type, size, and location of lung lesions have an effect on
      measurement errors. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 1 J. Magn.
      Reson. Imaging 2018;47:1003-1012.

PMID- 28741733
TI  - An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich
      repeat 13 and is recognized by a monoclonal antibody.
AB  - Lipopolysaccharide (LPS)-induced activation of Toll-like receptor 4 (TLR4)
      elicits the innate immune response and can trigger septic shock if excessive. Two
      antibodies (HT4 and HT52) inhibit LPS-induced human TLR4 activation via novel LPS
      binding-independent mechanisms. The HT52 epitope resides on leucine-rich repeat 2
      (LRR2) and is a feature of many inhibitory antibodies; antigen specificity of HT4
      does not reside in LRR2. Here, we identified an HT4 epitope on LRR13 located
      close to the TLR4 dimerization interface that plays a role in NFkappaB
      activation. HT4 and HT52 mutually enhanced TLR4 inhibition. LRR13 is a novel
      inhibitory epitope and may be useful for developing anti-TLR4 antibodies.
      Combination therapy with LRR2 and LRR13 may effectively inhibit TLR4 activation.

PMID- 28741734
TI  - Comparative study of TERT promoter mutation status within spatially, temporally
      and morphologically distinct components of urothelial carcinoma.

PMID- 28741735
TI  - Argon plasma coagulation for successful fragmentation and removal of an over-the
      scope clip.

PMID- 28741736
TI  - Increased Mindfulness Skills as Predictors of Reduced Trauma-Related Guilt in
      Treatment-Seeking Veterans.
AB  - The present study examined the predictive role of increased self-reported
      mindfulness skills on reduced trauma-related guilt in a sample of veterans over
      the course of residential treatment for posttraumatic stress disorder (PTSD; N =
      128). The residential treatment consisted of seven weeks of intensive cognitive
      processing therapy (CPT) for PTSD, as well as additional psychoeducational
      groups, including seven sessions on mindfulness skills. Increased mindfulness
      skills describing, acting with awareness, and accepting without judgment were
      significantly associated with reductions in trauma-related guilt over the course
      of treatment. Increases in the ability to act with awareness and accept without
      judgment were significantly associated with reductions in global guilt, R2 = .26,
      guilt distress, R2 = .23, guilt cognitions, R2 = .23, and lack of justification,
      R2 = .11. An increase in the ability to accept without judgment was the only self
      reported mindfulness skill that was associated with reductions in hindsight bias,
      beta = -.34 and wrongdoing, beta = -.44. Increases in self-reported mindfulness
      skills explained 15.1 to 24.1% of the variance in reductions in trauma-related
      guilt, suggesting that mindfulness skills may play a key role in reducing the
      experience of trauma-related guilt during psychotherapy. Our results provide
      preliminary support for the use of mindfulness groups as an adjunct to
      traditional evidence-based treatments aimed at reducing trauma-related guilt,
      though this claim needs to be tested further using experimental designs.

PMID- 28741737
TI  - Effect of exogenous progesterone administration on luteal sensitivity to PGF
      during the early development of the corpus luteum in mares and cows.
AB  - The objective of this study was to determine the effect of exogenous progesterone
      administration at ovulation and during the early development of the CL, on its
      future sensitivity to a single administration of PGF2a in mares and cows. Horse
      Retrospective reproductive data from an equine clinic in the UK during three
      breeding seasons were used. Mares were divided into: control group, cycles with
      single ovulations; double ovulation group cycles with asynchronous double
      ovulations; and PRID group: cycles with single ovulations and treatment with
      intravaginal progesterone device (CIDR) immediately after the ovulation. All
      mares were treated with d-cloprostenol (PGF) at either: (i) 88 hr; (ii) 96 hr;
      (iii) 104 hr; or (iv) 112 hr after the last ovulation. Cattle A total of nine non
      lactating Holstein cows were used. All cows were administered PGF14 d apart and
      allocated to one of two groups control group GnRH was administered 56 hr after
      the second PGF administration. CIDR group CIDR was inserted at the same time of
      GnRH administration. All cows were administered PGF at 120 hr post-ovulation. The
      complete luteolysis rate of mares with double ovulation (66.7%) and those treated
      with exogenous progesterone (68.4%) was significantly higher than the rate of
      mares with single ovulation (35.6%) at 104 hr. In the cow, however, the treatment
      with CIDR did not increase the luteolytic response in cows treated at 120 hr post
      ovulation. In conclusion, the degree of complete luteolysis can be influenced by
      increasing the concentration of progesterone during the early luteal development
      in mares.

PMID- 28741738
TI  - Aspergillus calidoustus case series and review of the literature.
AB  - Aspergillus calidoustus, previously classified as Aspergillus ustus, is an
      emerging pathogen in immunocompromised persons. We describe four recent cases of
      A. calidoustus and review 37 additional cases of A. calidoustus (n = 8) or A.
      ustus (n = 29) published through June 2016. Twenty (49%) cases occurred in
      patients with hematologic malignancy and/or receipt of hematopoietic cell
      transplantation, and 13 (32%) occurred in solid organ transplant recipients.
      Antifungal susceptibility was reported in 49% of cases and in 42% treatment
      failed. Overall mortality was 66% and, where reported, attributable mortality was
      30%. A. calidoustus infection is associated with a high mortality rate and
      frequently displays in vitro antifungal resistance.

PMID- 28741739
TI  - Reversible, Fast, and Wide-Range Oxygen Sensor Based on Nanostructured
      Organometal Halide Perovskite.
AB  - Nanostructured materials characterized by high surface-volume ratio hold the
      promise to constitute the active materials for next-generation sensors. Solution
      processed hybrid organohalide perovskites, which have been extensively used in
      the last few years for optoelectronic applications, are characterized by a self
      assembled nanostructured morphology, which makes them an ideal candidate for gas
      sensing. Hitherto, detailed studies of the dependence of their electrical
      characteristics on the environmental atmosphere have not been performed, and even
      the effect of a ubiquitous gas such as O2 has been widely overlooked. Here, the
      electrical response of organohalide perovskites to oxygen is studied.
      Surprisingly, a colossal increase (3000-fold) in the resistance of perovskite
      based lateral devices is found when measured in a full oxygen atmosphere, which
      is ascribed to a trap healing mechanism originating from an O2 -mediated iodine
      vacancies filling. A variation as small as 70 ppm in the oxygen concentration can
      be detected. The effect is fast (<400 ms) and fully reversible, making
      organohalide perovskites ideal active materials for oxygen sensing. The effect of
      oxygen on the electrical characteristics of organohalide perovskites must be
      taken into deep consideration for the design and optimization of any other
      perovskite-based (opto-) electronic device working in ambient conditions.

PMID- 28741740
TI  - Ultrafine, fine, and black carbon particle concentrations in California child
      care facilities.
AB  - Although many U.S. children spend time in child care, little information exists
      on exposures to airborne particulate matter (PM) in this environment, even though
      PM may be associated with asthma and other respiratory illness, which is a key
      concern for young children. To address this data gap, we measured ultrafine
      particles (UFP), PM2.5 , PM10 , and black carbon in 40 California child-care
      facilities and examined associations with potential determinants. We also tested
      a low-cost optical particle measuring device (Dylos monitor). Median
      (interquartile range) concentrations for indoor UFP, gravimetric PM2.5 , real
      time PM2.5 , gravimetric PM10 , and black carbon over the course of a child-care
      day were 14 000 (11 000-29 000) particles/cm3 , 15 (9.6-21) MUg/m3 , 15 (11-23)
      MUg/m3 , 48 (33-73) MUg/m3 , and 0.43 (0.25-0.65) ng/m3 , respectively. Indoor
      black carbon concentrations were inversely associated with air exchange rate
      (Spearman's rho = -.36) and positively associated with the sum of all Gaussian
      adjusted traffic volume within a one-kilometer radius (Spearman's rho = .45) (P
      values <.05). Finally, the Dylos may be a valid low-cost alternative to monitor
      PM levels indoors in future studies. Overall, results indicate the need for
      additional studies examining particle levels, potential health risks, and
      mitigation strategies in child-care facilities.

PMID- 28741741
TI  - Addiction-related interactions of pregabalin with morphine in mice and humans:
      reinforcing and inhibiting effects.
AB  - The gabapentinoid pregabalin is a rapid-acting anxiolytic and analgesic, possibly
      suitable in supervised opioid detoxification. However, clinicians have been
      cautious in using it because of its unknown addictive risk and rising number of
      mortalities after pregabalin self-medication in opioid abusers. Here, we studied
      interactions of pregabalin and morphine on reward functions of the dopamine
      system in mice and the efficacy of pregabalin on withdrawal in opioid addicts.
      After the treatment of mice with pregabalin and morphine, we used
      electrophysiology to study neuroplasticity in midbrain slices, self
      administration and conditioned place preference tests to investigate the
      rewarding potential of pregabalin and naloxone-precipitated morphine withdrawal
      to evaluate opioid withdrawal symptoms. Further, we ran a pilot single-blind,
      randomized, controlled trial (34 heroin addicts) to evaluate the efficacy and
      safety of pregabalin in the treatment of opioid withdrawal syndrome. Pregabalin
      alone did not induce glutamate receptor neuroplasticity of dopamine neurons in
      the ventral tegmental area, but pre-treatment with pregabalin suppressed morphine
      induced neuroplasticity, hyperlocomotion and morphine self-administration.
      Pregabalin administration after chronic morphine exposure failed to induce any
      rewarding effects. Instead, pregabalin suppressed withdrawal symptoms in both
      morphine-treated mice and opioid addicts and was well tolerated. Intriguingly,
      pregabalin administration after a low dose of morphine strongly facilitated
      ventral tegmental area neuroplasticity and led to increased conditioned place
      preference. Pregabalin appears to have the efficacy to counteract both
      reinforcing and withdrawal effects of opioids, but it also has a potentiating
      effect when given to mice with existing opioid levels.

PMID- 28741742
TI  - Dental and skeletal maturation in female adolescents with temporomandibular joint
      osteoarthritis.
AB  - Occurrence of temporomandibular disorders (TMDs) and temporomandibular joint
      (TMJ) osteoarthritis (OA) during adolescence may have interactions with
      mandibular and dental development. The aim of the present study was to
      investigate relationships between occurrence of TMD and TMJ OA and extents of
      dental and skeletal development in juvenile female patients. In total, 95 female
      adolescents (age range, 11-15 years) were selected. Among them, 15 subjects
      (control) had no signs of TMD, 39 TMD patients did not have OA (TMDnoOA), 17 TMD
      patients were at initial stage of TMJ OA (TMJOA), and 27 patients showed
      progressive stage of TMJ OA (TMJOA). Dental age was estimated by Demirjian's
      stages used in a previous study with Korean adolescents. Craniofacial parameters
      and cervical vertebrae maturation (CVM) stages, representing skeletal maturity
      levels, were measured using lateral cephalograms. The estimated dental age was
      significantly lower than chronological age in all groups, but CVM differences
      were not statistically significant. Dental age was the lowest, and differences
      between the chronological age and estimated dental age were the highest among
      initial stage of TMJOAs followed by progressive stage of TMJOAs, TMDnoOAs and
      control and were not associated with CVM stages. Cephalometric parameters
      revealed significant clockwise rotation of the mandible among the TMJOAs compared
      with controls and TMDnoOAs and were not associated with CVM stages as well. The
      juvenile female patients with TMD, particularly TMJ OA, showed retarded dental
      development, mandibular backward positioning and hyperdivergent facial profiles.
      The TMJ OA may be associated with retarded dental development but not with
      skeletal maturations.

PMID- 28741743
TI  - Indoor air problems and experiences of injustice in the workplace: A quantitative
      and a qualitative study.
AB  - This study explores subjective injustice experiences of individuals suffering
      from suspected or observed indoor air problems in their workplaces in two
      studies. We focus on injustice experiences because they influence how individuals
      cope with and recover from health problems. The first study reports associations
      between the perceived harmfulness of the indoor environment (ie, mold/inadequate
      ventilation) and subjective injustice experiences in workplaces in a
      representative sample of Finnish working-aged people (N = 4633). Altogether, 37%
      of the respondents perceived their workplaces' indoor environments to be harmful.
      Multivariate logistic regression analyses revealed that the risks of reporting
      subjective injustice experiences (eg, information, attitudes, and remuneration)
      were significantly higher for those reporting harmful indoor environments
      compared to those who reported no such problems (OR 1.28-1.95 for different
      situations). The second study explored injustice experiences more closely by
      qualitatively analyzing the content of 23 essays. These essays were written by
      people who suffered from suspected or observed indoor air problems in their
      workplaces. The respondents reported multidimensional experiences of injustice,
      which related to conflicts, and moral exclusions. Awareness of these psychosocial
      effects is important for the prevention of unnecessary escalation of psychosocial
      problems in workplaces with observed and suspected indoor air problems.

PMID- 28741744
TI  - Thermal suit in preventing unintentional intraoperative hypothermia during
      general anaesthesia: a randomized controlled trial.
AB  - BACKGROUND: Unintentional perioperative hypothermia causes serious adverse
      effects to surgical patients. Thermal suit (T-Balance(r) ) is an option for
      passive warming perioperatively. We hypothesized that the thermal suit will not
      maintain normothermia more efficiently than conventional cotton clothes when also
      other preventive procedures against unintentional hypothermia are used. METHODS:
      One hundred patients were recruited to this prospective, randomized trial. They
      were allocated to the Thermal Suit group or a Control group wearing conventional
      hospital cotton clothes. All patients received our institution's standard
      treatment against unintentional hypothermia including a warming mattress, a
      forced-air upper body warming blanket and a warming device for intravenous
      fluids. Eardrum temperature was measured pre-operatively. In the operating room
      and post-anaesthesia care unit temperatures were measured from four locations:
      oesophagus, left axilla, dorsal surface of the left middle finger and dorsum of
      the left foot. The primary outcome measure was temperature change during robotic
      assisted laparoscopic radical prostatectomy. RESULTS: The temperatures of 96
      patients were analysed. There was no difference in mean core temperatures,
      axillary temperatures or skin temperatures on the finger between the groups. Only
      foot dorsum temperatures were significantly lower in the Thermal Suit group.
      Intraoperative temperature changes were similar in both groups. In the post
      anaesthesia care unit temperature changes were minimal and they did not differ
      between the groups. CONCLUSION: Provided that standard preventive procedures in
      maintaining normothermia are effective the thermal suit does not provide any
      additional benefit over conventional cotton clothes during robotic-assisted
      laparoscopic radical prostatectomy.

PMID- 28741745
TI  - Venous thromboembolism prophylaxis in urology: A review.
AB  - Venous thromboembolism is potentially a lethal problem, and is associated with
      chronic morbidity. Venous thromboembolism is frequently diagnosed after
      urological surgery, yet the role of perioperative venous thromboembolism
      prophylaxis is not clearly defined. Any current recommendations are largely based
      on evidence derived from other surgical specialties. Even within different
      guidelines, there remains significant variation, suggesting a consensus is
      required. The present review aims to define the problem of venous thromboembolism
      within the urological population, and identifies patients at risk. It evaluates
      the role of various types of mechanical and pharmacological prophylaxis, along
      with its timing and duration of administration in common urological operations.
      The current guidelines are summarized and compared in order to give the reader a
      better perspective of this vital condition.

PMID- 28741746
TI  - Skin lesion in a patient after hematopoietic stem cell transplant.
AB  - We present a case of a 61-year-old Caucasian woman who was hospitalized with
      fever on day 176 after a matched unrelated stem cell transplant for acute
      myelogenous leukemia. She developed hemorrhagic bullae on the skin of her right
      thigh, and both blood cultures and skin biopsy confirmed Fusarium proliferatum.
      Despite antifungal therapy, her condition worsened and she died while on comfort
      only measures.

PMID- 28741747
TI  - Defending the scientific integrity of conservation-policy processes.
AB  - Government agencies faced with politically controversial decisions often discount
      or ignore scientific information, whether from agency staff or nongovernmental
      scientists. Recent developments in scientific integrity (the ability to perform,
      use, communicate, and publish science free from censorship or political
      interference) in Canada, Australia, and the United States demonstrate a similar
      trajectory. A perceived increase in scientific-integrity abuses provokes
      concerted pressure by the scientific community, leading to efforts to improve
      scientific-integrity protections under a new administration. However, protections
      are often inconsistently applied and are at risk of reversal under
      administrations publicly hostile to evidence-based policy. We compared recent
      challenges to scientific integrity to determine what aspects of scientific input
      into conservation policy are most at risk of political distortion and what can be
      done to strengthen safeguards against such abuses. To ensure the integrity of
      outbound communications from government scientists to the public, we suggest
      governments strengthen scientific integrity policies, include scientists' right
      to speak freely in collective-bargaining agreements, guarantee public access to
      scientific information, and strengthen agency culture supporting scientific
      integrity. To ensure the transparency and integrity with which information from
      nongovernmental scientists (e.g., submitted comments or formal policy reviews)
      informs the policy process, we suggest governments broaden the scope of
      independent reviews, ensure greater diversity of expert input and transparency
      regarding conflicts of interest, require a substantive response to input from
      agencies, and engage proactively with scientific societies. For their part,
      scientists and scientific societies have a responsibility to engage with the
      public to affirm that science is a crucial resource for developing evidence-based
      policy and regulations in the public interest.

PMID- 28741748
TI  - Porous Organic Polymers for Post-Combustion Carbon Capture.
AB  - One of the most pressing environmental concerns of our age is the escalating
      level of atmospheric CO2 . Intensive efforts have been made to investigate
      advanced porous materials, especially porous organic polymers (POPs), as one type
      of the most promising candidates for carbon capture due to their extremely high
      porosity, structural diversity, and physicochemical stability. This review
      provides a critical and in-depth analysis of recent POP research as it pertains
      to carbon capture. The definitions and terminologies commonly used to evaluate
      the performance of POPs for carbon capture, including CO2 capacity, enthalpy,
      selectivity, and regeneration strategies, are summarized. A detailed correlation
      study between the structural and chemical features of POPs and their adsorption
      capacities is discussed, mainly focusing on the physical interactions and
      chemical reactions. Finally, a concise outlook for utilizing POPs for carbon
      capture is discussed, noting areas in which further work is needed to develop the
      next-generation POPs for practical applications.

PMID- 28741749
TI  - Clinical outcomes after local field conformal reirradiation of patients with
      retropharyngeal nodal metastasis.
AB  - BACKGROUND: The purpose of this study was to present our experience with
      retropharyngeal node reirradiation using highly conformal radiotherapy (RT).
      METHODS: A retrospective screen of 2504 consecutively irradiated patients with
      head and neck malignancies between 2005 and 2015 identified 19 patients who
      underwent reirradiation for retropharyngeal node metastasis. Clinical and
      toxicity outcomes were assessed in these patients. RESULTS: Thirteen patients
      (68%) had squamous cell carcinoma. Eleven patients (58%) received conventionally
      fractionated intensity-modulated radiotherapy (IMRT) or proton therapy, and 8
      patients (42%) received single-fractionated or hypofractionated stereotactic RT.
      Fourteen patients (74%) received chemotherapy. Median follow-up was 14.7 months.
      The 1-year local control, locoregional control, overall survival, and progression
      free survival rates were 100%, 94%, 92%, and 92%, respectively. Three patients
      (16%) experienced acute grade 3 toxicity and occurred in those treated with IMRT.
      There was no late grade >=3 toxicity. CONCLUSION: Retropharyngeal node
      reirradiation with conformal therapy is well tolerated and associated with
      excellent short-term disease control.

PMID- 28741750
TI  - Atypical morphology of anogenital warts is not a marker of atypical histology or
      of infection to the high-risk human papillomavirus genotypes.
AB  - BACKGROUND: The clinical morphology of anogenital warts may vary from flat,
      filiform, papular, or verrucous to giant condyloma acuminatum. Clinically
      atypical-looking genital warts may alarm the clinician because of their suspected
      malignant potential, which may cause anxiety, often leading to aggressive
      interventions. OBJECTIVE: To study if clinically atypical-looking anogenital
      warts are more likely to be premalignant or malignant as compared to typical
      warts. METHOD: Data of 41 (37 males, 4 females) patients with anogenital warts
      was retrospectively analyzed. After a detailed literature review and in-house
      discussions, criteria for anogenital warts with typical and atypical clinical
      morphology were defined. Clinical photographs were independently reviewed by
      three dermatologists, and human papillomavirus (HPV) genotyping results,
      histological evaluation, and immunohistochemical analysis for p53 expression were
      evaluated. RESULTS: Fifteen (36.6%) anogenital warts were classified as atypical
      by at least two of three blinded dermatologists. The histological examination
      showed mitotic figures in 31/41 (75.6%) specimens, dysplasia in 14/41 (44.1%)
      specimens, and p53 positivity in 34/41 (82.9%) specimens. There was no
      significant difference in the high-risk HPV genotyping (P = 0.67), frequency of
      dysplastic changes on histology (P = 0.19), and immunohistochemistry with p53 (P
      = 0.08) between clinically typical and atypical-appearing anogenital warts.
      Similarly, no significant difference was found in the frequency of dysplastic
      changes (P = 0.67) or p53 expressions (P =0.41) based on the HPV genotypes.
      CONCLUSIONS: The atypical clinical morphology of anogenital warts may not be a
      marker of increased malignant potential. High-risk HPV genotypes do not have a
      statistically significant association with dysplasia or positive
      immunohistochemistry with p53.

PMID- 28741751
TI  - Assessment of diastolic function of normal fetal heart using dual-gate Doppler.
AB  - OBJECTIVES: The ratio of mitral peak early diastolic filling to early diastolic
      mitral annular velocity (E/e') reflects diastolic cardiac function in adults.
      Dual-gate Doppler (DD) enables measurements of E/e' in the same heart beat. This
      study was designed to assess the utility of the DD method for measurement of
      fetal E/e' and determine reference ranges for normal fetuses. METHODS: This
      prospective study comprised normal singleton pregnancies undergoing fetal
      echocardiography between 16 and 36 weeks of gestation. According to the DD
      method, E-wave velocity on pulsed-wave Doppler and e'-wave on tissue Doppler
      imaging were measured simultaneously on an apical or basal four-chamber view, and
      fetal E/e' was calculated. Spearman's correlation coefficient was used to assess
      the relationship between gestational age (GA) and E-wave and e'-wave velocities
      and E/e'. RESULTS: A total of 133 pregnancies were included in this study and all
      E/e' measurements were successful. Significant correlation was observed between
      GA and both left ventricular (LV) E/e' (r s  = -0.666, P < 0.001) and right
      ventricular (RV) E/e' (r s  = -0.607, P < 0.001). The regression equations for
      bilateral E/e' were: LV-E/e' = 17.341 - 0.631GA + 0.008 * GA2 (mean +/- SD, R 2 
      = 0.440 +/- 1.333); and RV-E/e' = 19.156 - 0.794GA + 0.012GA2 (R 2  = 0.419 +/-
      1.329). CONCLUSIONS: Bilateral E/e' of normal fetuses, measured using the DD
      method, decreased with GA, which is considered to be related to myocardial
      maturity. DD is a useful and convenient method for evaluating fetal E/e' in order
      to assess diastolic function in the prenatal period. Copyright (c) 2017 ISUOG.
      Published by John Wiley & Sons Ltd.

PMID- 28741752
TI  - What does it cost to feed aged care residents in Australia?
AB  - AIM: Funding cuts to the aged care industry impact catering budgets and aged care
      staffing levels, which may in turn affect the nutritional status of aged care
      residents. This paper reports average food expenditure and trends in Australian
      residential aged care facilities (RACFs). METHODS: This is a retrospective study
      collecting RACFs' economic outlay data through a quarterly online survey
      conducted over the 2015 and 2016 financial years. RESULTS: Data were compiled
      from 817 RACFs, representing 64 256 residential beds and 23 million bed-days
      Australia-wide. The average total spend in Australian Dollars (AUD) on catering
      consumables (including cutlery/crockery, supplements, paper goods) was $8.00 per
      resident per day (prpd) and $6.08 prpd when looking at the raw food and
      ingredients budget alone. Additional data from over half the RACFs (n = 456, 56%)
      indicate a 5% decrease in food cost ($0.31 prpd) in the last year, particularly
      in fresh produce, with a simultaneous 128% ($0.50 prpd) increase in cost for
      supplements and food replacements. Current figures are comparatively less than
      aged care food budgets internationally (US, UK and Canada), less than community
      dwelling older adults ($17.25 prpd) and 136% less than Australian corrective
      services ($8.25 prpd). CONCLUSIONS: The current spend on food in RACFs has
      decreased compared with previous years, reflecting an increasing reliance on
      supplements, and is significantly less than current community food spend.

PMID- 28741753
TI  - Phytochemical and Bioactive Potential of in vivo and in vitro Grown Plants of
      Centaurea ragusina L. - Detection of DNA/RNA Active Compounds in Plant Extracts
      via Thermal Denaturation and Circular Dichroism.
AB  - INTRODUCTION: The phytochemical composition and biological activity of non
      volatile components of Centaurea ragusina L. has not been studied previously.
      OBJECTIVES: Our aim was to evaluate the phytochemical and bioactive potential
      (including interactions with polynucleotides) of C. ragusina L. depending on the
      origin of plant material (in vivo - leaves from natural habitats, ex vitro -
      leaves from plants acclimated from culture media, in vitro - leaves and calli
      from plants grown in culture media) and polarity of solvents used in extract
      preparation (80 and 96% ethanol and water combinations or single solvents).
      METHODOLOGY: The polyphenol composition was determined by spectrophotometric and
      HPLC analysis. Biological activity of extracts was evaluated by following
      methods: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 1,1
      diphenyl-2-picrylhydrazyl (DPPH) methods for antioxidative activity, 2,3,5
      triphenyl tetrazolium chloride (TTC) microdilution method for antibacterial
      activity, crystal-violet test for cytotoxic activity and thermal denaturation
      (TD) and circular dichroism (CD) for DNA/RNA interactions. RESULTS: Conditions
      for the most efficient polyphenol extraction were determined: the 80%
      ethanol/water solvent system was the most suitable for callus and leaf ex vitro
      samples and 80 or 96% ethanol for leaf in vivo samples. Significantly higher
      levels of chlorogenic acid and naringenin were detected in callus tissue than in
      vivo plant. Ethanolic extracts exhibited the significant antibacterial activity
      against Staphylococcus aureus ATCC 25923. DNA/RNA active compounds in plant
      extracts were detected by TD and CD methods. CONCLUSIONS: Callus tissue and ex
      vitro leaves represent a valuable source of polyphenols as in vivo leaves. TD and
      CD can be applied for detection of DNA/RNA active compounds in extracts from
      natural resources. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28741754
TI  - Potential utility of pulsed-wave Doppler for prenatal diagnosis of fetal
      ventricular tachycardia secondary to long QT syndrome.

PMID- 28741755
TI  - Soft-tissue mass of fetal scalp with abnormal course of dural sinuses.

PMID- 28741756
TI  - Structure of the defensin NsD7 in complex with PIP2 reveals that defensin : lipid
      oligomer topologies are dependent on lipid type.
AB  - Defensins are innate immune molecules that upon recognition of specific
      phospholipids can disrupt microbial membranes by forming oligomeric assemblies.
      Structures of two related plant defensins, NaD1 and NsD7, bound to
      phosphatidylinositol 4,5-bisphosphate (PIP2 ) and phosphatidic acid (PA),
      respectively, revealed striking differences in their oligomeric topologies. To
      understand how NsD7 binds different phospholipids and rationalize the different
      topologies, we determined the structure of an NsD7-PIP2 complex. This structure
      reveals fundamental differences in phospholipid binding compared to NsD7-PA, and
      an oligomeric topology nearly identical to the previously determined NaD1-PIP2
      complex, establishing that the PIP2 fibril topology is conserved between NaD1 and
      NsD7. Our findings highlight the remarkable ability of defensins to bind
      different types of phospholipids to form oligomeric fibrils with diverse
      topologies.

PMID- 28741757
TI  - Equivalent missense variant in the FOXP2 and FOXP1 transcription factors causes
      distinct neurodevelopmental disorders.
AB  - The closely related paralogues FOXP2 and FOXP1 encode transcription factors with
      shared functions in the development of many tissues, including the brain.
      However, while mutations in FOXP2 lead to a speech/language disorder
      characterized by childhood apraxia of speech (CAS), the clinical profile of FOXP1
      variants includes a broader neurodevelopmental phenotype with global
      developmental delay, intellectual disability, and speech/language impairment.
      Using clinical whole-exome sequencing, we report an identical de novo missense
      FOXP1 variant identified in three unrelated patients. The variant, p.R514H, is
      located in the forkhead-box DNA-binding domain and is equivalent to the well
      studied p.R553H FOXP2 variant that cosegregates with CAS in a large UK family. We
      present here for the first time a direct comparison of the molecular and clinical
      consequences of the same mutation affecting the equivalent residue in FOXP1 and
      FOXP2. Detailed functional characterization of the two variants in cell model
      systems revealed very similar molecular consequences, including aberrant
      subcellular localization, disruption of transcription factor activity, and
      deleterious effects on protein interactions. Nonetheless, clinical manifestations
      were broader and more severe in the three cases carrying the p.R514H FOXP1
      variant than in individuals with the p.R553H variant related to CAS, highlighting
      divergent roles of FOXP2 and FOXP1 in neurodevelopment.

PMID- 28741758
TI  - Stem cell-derived exosomes: A promising strategy for fracture healing.
AB  - OBJECTIVES: To describe the biological characteristics of exosomes and to
      summarize the current status of stem cell-derived exosomes on fracture healing.
      Meanwhile, future challenges, limitations and perspectives are also discussed.
      METHODS: Search and analyze the related articles in pubmed database through the
      multi-combination of keywords like "stem cells","exosomes","bone regeneration"
      and "fracture healing". CONCLUSION: Stem cell-derived exosome therapy for
      fracture healing has been enjoying popularity and is drawing increasing
      attention. This strategy helps to promote proliferation and migration of cells,
      as well as osteogenesis and angiogenesis, in the process of bone formation.
      Although the exact mechanisms remain elusive, exosomal miRNAs seem to play vital
      roles. Future studies are required to solve multiple problems before clinical
      application, including comprehensive and thorough understanding of exosomes, the
      exact roles of exosomes in regulating bone formation, and the optimal source,
      dose and frequency of treatment, as well as technical and safety issues.
      Moreover, studies based on fracture models of large animals are could offer
      guidance and are in demand.

PMID- 28741759
TI  - Glutamine synthetase isozymes in germinating barley seeds.
AB  - Glutamine synthetase (GS; EC 6.3.1.2) is a key enzyme of ammonia assimilation in
      higher plants. In the present study the subunit composition and localization of
      GS in germinating barley (Hordeum vulgare) seed have been clarified. Analysis of
      the GS polypeptide composition by immunoblotting revealed two different
      polypeptides. A and B, with a molecular mass of 42 and 40 kDa, respectively. In
      the scutellum subunit A was already present in the ungerminated seed and remained
      unchanged, whereas subunit B appeared on day 2 and increased about 5-fold during
      germination. Polypeptide B also appeared later during germination in the aleurone
      layer, roots and weakly in the etiolated shoots. By immunogold microscopy, GS was
      detected in the scutellum and the aleurone layer of barley seeds during
      germination. Subcellular localization of GS on ultrathin cryosections showed that
      a cytosolic isozyme was present in the scutellum. Our study confirms that only a
      cytosolic GS is expressed in barley seed, and its subunit composition changes
      during germination.

PMID- 28741760
TI  - Daylength and thermal time responses of budburst during dormancy release in some
      northern deciduous trees.
AB  - Dormancy release and thermal time to budburst as affected by duration of chilling
      outdoors, followed by different flushing temperatures and daylengths in a
      phytotron, were studied in cuttings of several northern tree species. In Betula
      pubescens, B. pendula and Prunus padus vegetative buds were released from
      dormancy already in December, in Populus tremula in January, whereas in Alnus
      incana and A. glutinosa dormancy was not released until February. Thermal time
      (day degrees >0 degrees C) to budburst decreased non-linearily with increasing
      duration of chilling (i. e. duration outdoors), and the slope of this
      relationship differed among species. The estimated effective base temperature for
      accumulation of thermal time varied from + 1 degrees C in P. tremula to -4
      degrees C in P. padus. The use of 0 degrees C as base temperature is recommended.
      Long days reduced the thermal time to budburst at all flushing temperatures (9,
      15 and 21 degrees C) in all the above species and in Corylus avellana, whereas
      Sorbus aucuparia and Rubus idaeus showed no daylength response. Since the
      chilling requirement of all species was far exceeded even in a winter with
      January-March temperatures 6.5 degrees C above normal, it is concluded that under
      Scandinavian conditions, the main effect of climatic warming would be earlier
      budburst and, associated with that, a longer growing season and increased risk of
      spring frost injury.

PMID- 28741761
TI  - Oxygen influences benzyladenine and 2,4-dichlorophenoxyacetic acid levels in
      cultured embryogenic tissue of Norway spruce.
AB  - It is known that reducing the partial pressure of O2 influences the induction of
      somatic embryogenesis. We tested the hypothesis that O2 causes changes in the
      endogenous levels of exogenously supplied benzyladenine (BA) or 2,4
      dichlorophenoxyacetic acid (2,4-D). Embryogenic tissue of Picea abies was
      incubated under reduced (2.5, 5 kPa) and ambient (21 kPa) levels of O2 for 1, 3,
      7 and 11 days and the endogenous concentrations of BA and 2,4-D were measured.
      For all treatments the concentration of BA in the tissue increased until the
      third day. At day 3, the ratio of BA in the tissue relative to the initial
      concentration in the medium, was 3.9, 2.8 and 1.9 for tissue incubated under 2.5,
      5 and 21 kPa O2 , respectively. The BA concentration then declined gradually.
      Uptake of 2,4-D was inhibited at low O2 levels. However, 2,4-D gradually
      accumulated in tissue grown under hypoxia, so that high levels were reached by
      day 11. These shifts in the BA and 2,4-D levels also caused a transient increase
      in the BA to 2,4-D ratio in tissue incubated under hypoxia. Although relevant for
      the previously reported effects of oxygen on induction of embryogenic tissue, it
      is unlikely that oxygen-induced alterations in BA and 2,4-D levels alone suffice
      to explain these findings.

PMID- 28741762
TI  - Characterization of the laser-induced blue, green and red fluorescence signatures
      of leaves of wheat and soybean grown under different irradiance.
AB  - The blue, green and red fluorescence emission of green wheat (Triticum aestivum
      L. var. Rector) and soybean leaves (Glycine max L. var. Maple Arrow) as induced
      by UV light (nitrogen laser: 337 nm) was determined in a phytochamber and in
      plants grown in the field. The fluorescence emission spectra show a blue maximum
      near 450 nm, a green shoulder near 530 nm and the two red chlorophyll
      fluorescence maxima near 690 and 735 nm. The ratio of blue to red fluorescence,
      F450/F690, exhibited a clear correlation to the irradiance applied during the
      growth of the plants. In contrast, the chlorophyll fluorescence ratio, F690/F735,
      and the ratio of blue to green fluorescence, F450/F530, seem not to be or are
      only slightly influenced by the irradiance applied during plant growth. The blue
      fluorescence F450 only slightly decreased, whereas the red chlorophyll
      fluorescence decreased with increasing irradiance applied during growth of the
      plants. This, in turn, resulted in greatly increased values of the ratio,
      F450/F690, from 0.5 - 1.5 to 6.4 - 8.0. The decrease in the chlorophyll
      fluorescence with increasing irradiance seems to be caused by the accumulation of
      UV light absorbing substances in the epidermal layer which considerably reduces
      the UV laser light which passes through the epidermis and excites the chlorophyll
      fluorescence of the chloroplasts in the subepidermal mesophyll cells.

PMID- 28741763
TI  - Genotype-specific differences in chilling tolerance of maize in relation to
      chilling-induced changes in water status and abscisic acid accumulation.
AB  - Four inbred maize lines differing in chilling tolerance were used to study
      changes in water status and abscisic acid (ABA) levels before, during and after a
      chilling period. Seedlings were raised in fertilized soil at 24/22 degrees C
      (day/night), 70% relative humidity. and a 12-h photoperiod with 200 MUmol m-2 s-1
      from fluorescent tubes. At an age of 2 weeks the plants were conditioned at 14/12
      degrees C for 4 days and then chilled for 5 days at 5/3 degrees C. The other
      conditions (relative humidity, quantum flux, photoperiod) were unchanged. After
      the chilling period the plants were transferred to the original conditions for
      recovery. The third leaves were used to study changes in leaf necrosis, ion
      efflux, transpiration, water status and ABA accumulation. Pronounced differences
      in chilling tolerance between the 4 lines as estimated by necrotic leaf areas,
      ion efflux and whole plant survival were observed. Conditioning significantly
      increased tolerance against chilling at 5/3 degrees C in all genotypes. The
      genotypes with low chilling tolerance had lower water and osmotic potentials than
      the more tolerant genotypes during a chilling period at 5/3 degrees C. These
      differences were related to higher transpiration rates and lower diffusive
      resistance values of the more susceptible lines. During chilling stress at 5/3
      degrees C ABA levels were quadrupled. Only a small rise was measurable during
      conditioning at 14/12 degrees C. However, conditioning enhanced the rise of ABA
      during subsequent chilling. ABA accumulation in the two lines with a higher
      chilling tolerance was triggered at a higher leaf water potential and reached
      higher levels than in the less tolerant lines. We conclude that chilling
      tolerance in maize is related to the ability for fast and pronounced formation of
      ABA as a protective agent against chilling injury.

PMID- 28741764
TI  - Carbohydrate content and glycosidase activities following cold hardening in two
      grass species.
AB  - The freezing resistance of the grass species Phleum pratense L. (timothy) and
      Phalaris arundinaces L. increases significantly after cold hardening. The content
      and composition of soluble carbohydrates were determined in the plants after
      short day treatment, cold hardening and dehardening. The amounts of mono-, di-
      and trisaccharides were reduced during the short day treatment, increased during
      cold hardening and decreased again during dehardening. The total amounts of
      soluble carbohydrates (mono-, di-, tri- and polysaccharides) were the same in
      hardened and dehardened plants, indicating that during hardening soluble
      polysaccharides (fructose polymers, fructans) were converted to mono- and
      oligosaccharides. Sucrose increased most after hardening conditions and, in P.
      arundinacea, a significant increase in 1-F-fructosylsucrose (isokestose) was also
      observed. Invertase (beta-fructofuranosidase. EC 3.2.1.26) activity increased
      following cold hardening and decreased following dehardening, while the alpha
      galactosidase (EC 3.2.1.22) activity seemed to increase after dehardening. The
      glycosidases are probably involved in the mobilisation of polysaccharides during
      cold hardening.

PMID- 28741765
TI  - Content of low-molecular-weight thiols during the imbibition of Pea seeds.
AB  - The metabolism of low-molecular-weight thiols was investigated in seeds of Pisum
      sativum L. cv. Kleine Rheinlanderin during imbibition in water for 14 h. The
      amount of oxidized glutathione (GSSG) decreased from 319 nmol (g dry weight)-1 in
      dry seeds to 38 nmol (g dry weight)-1 within the first 14 h of imbibition. The
      decrease may have been due to the reduction of GSSG to reduced glutathione (GSH),
      catalyzed by the enzyme glutathione reductase (GR; EC 1.6.4.2). The enzyme
      activity was high in dry seeds [25 nkat (g dry weight)-1 ] and decreased to 20
      nkat (g dry weight)-1 within 14 h of imbibition. The activity of glucose-6
      phosphate dehydrogenase (EC 1.1.1.49) decreased from 100 nkat (g dry weight)-1 in
      dry seeds to 67 nkat (g dry weight)-1 after 14 h of imbibition. Within 14 h the
      amount of gamma-glutamyl-cysteine (gamma-GC) decreased from 135 to 38 nmol (g dry
      weight)-1 , whereas the cysteine content rose from 81 nmol (g dry weight)-1 in
      dry seeds to a maximum of 170 nmol (g dry weight)-1 after 12 h of imbibition,
      which may be due to the degradation of gamma-GC into cysteine.

PMID- 28741766
TI  - Electroporation of rapeseed protoplasts - transient and stable transformation.
AB  - Protoplasts of Brassica napus hypocotyls were transfected using electroporation.
      Parameters such as discharge potential, protoplast density and buffer
      constituents were tested to determine the most suitable conditions for gene
      transfer. To monitor the introduction of DNA into protoplasts a plasmid
      containing the beta-glucuronidase (EC 3.2.1.31), and the neomycin
      phospotransferase (EC 2.7.1.95) genes was used. By using this construct,
      expression of a screenable marker gene for transient expression analysis as well
      as an antibiotic resistance marker gene for selection of stable transformants
      were obtained. Refined electroporation conditions resulted in a frequency of 0.1%
      transiently transformed protoplasts. Microcalluses were cultured under selective
      conditions in a bead-type culture system. Resistant callus, with an absolute
      transformation frequency of 4.9 * 10-5 and a relative transformation frequency of
      0.3% could be achieved. X-ray irradiation of newly electroporated protoplasts did
      not enhance absolute transformation frequencies. From some of the resistant
      calluses, transgenic plants could be regenerated which were characterized by
      molecular analysis.

PMID- 28741767
TI  - Transient changes in length and growth of wheat coleoptile segments following
      treatments with osmotica and auxin.
AB  - The dependence of elongation on the osmotic potential of the medium was
      investigated, using coleoptile segments (CS) of Triticim aestivum L. (cv. Hartri)
      and an optoelectronic device. The study aimed at separating the osmoelastic
      response from the irreversible growth response when an osmoticum (mannitol) was
      added, and to compare both processes in order to consider the possibility of
      growth-induced reduction in turgor pressure. The prompt inhibition of elongation
      registered just after addition of 50 mM mannitol as well as the subsequent
      resumption of the original elongation rate could be quantitatively explained by
      the extent and the kinetics of the osmoelastic relaxation. An initial reduction
      in the irreversible elongation component by mild osmotic stress could not be
      demonstrated. Above a critical value, the irrevesible growth was insensitive to a
      further increase in water potential. The minimum turgor pressure required to
      drive steady growth was not far from zero in both the presence and absence of
      auxin. The rate (r) of osmotically caused shortening per unit change of water
      potential [Formula: see text] was determined from the kinetics of CS shortening
      induced by addition of mannitol at nearly isotonic concentration (300 mM). This
      parameter relates a fractional change in length to the difference in water
      potential between inside and outside, and was assumed to depend largely on the
      hydraulic resistance of the tissue and cuticle. It was found to be independent of
      IAA. The relatively low value of Gamma suggests significant reduction of turgor
      at high growth rates. In accordance with this conclusion, the extent of
      osmoelastic shortening after a transfer to 300 mM mannitol (dependent on wall
      strain) was significantly decreased in the presence of IAA. Addition of 100 MUM
      IAA to CS growing at a constant rate induced pronounced oscillations in the rate
      of elongation, which may be connected with the change in elastic cell wall
      strain. Whereas the steady state growth rate before the addition of IAA was the
      same in the presence and in the absence of 50 mM mannitol, the maximum growth
      rate found after addition of IAA was substantially reduced in the mannitol
      variant.

PMID- 28741768
TI  - The effects of cadmium on photosynthesis of Phaseolus vulgaris - a fluorescence
      analysis.
AB  - Bean plants (Phaseolus vulgaris L. cv. Scarlett), germinated in darkness for I
      week, were transferred to light (200 MUmol m-2 s-1 ) and cultivated for I week in
      a complete nutrient solution. After this period, cadmium ions in the form of
      CdSO4 were added at the concentrations of 0.10.20 and 50 MUM. The effects of this
      metal on the properties of photosystem II photochemistry were studied by means of
      modulated fluorescence analysis. Steady state photochemical quenching. non
      photochemical quenching and terminal fluorescence were determined in control and
      cadmiumtreated plants. We postulate that, during short term exposure of plants to
      cadmium in the early stages of growth, the Calvin cycle reactions are more likely
      than photosystem II to be the primary target of the toxic influence of cadmium.
      The reduced demand for ATP and NADPH upon Calvin cycle inhibition causes a down
      regulation of photosystem II photochemistry and of the yield of linear electron
      transport.

PMID- 28741769
TI  - Foliar uptake of Cd by pea (Pisum sativum) and sugar beet (Beta vulgaris).
AB  - Pea (Pisum sativum L. cv. Fenomen) and sugar beet (Beta vulgaris L. cv. Monohill)
      were cultivated in nutrient media without or with 10 MUM CdCl2 . Leaves of the
      same size and stage of development, detached or still attached to the intact
      plants, were submerged into redistilled water containing 1 to 250 MUM CdCl2 . The
      uptake experiments were run for 1 to 8 h at pH 3.6 and 5.1. Cuticular
      transpiration rate, density of leaf and density of stomata were also measured.
      Percentage of open stomata was studied at different pH. Foliar uptake of Cd into
      the leaf is evident since Cd is transported from the exposed part of the pea
      leaves, through the petioles and into the stipules, and since the Cd
      concentration of the leaves increases with time and external Cd concentration.
      The foliar uptake depends on the permeability of the cuticular membrane, which is
      increased by a high intrinsic Cd level, which in turn enhances the foliar uptake
      of Cd in sugar beet. Higher cuticular permeability in pea than in sugar beet is
      shown by a 2.5 times higher cuticular transpiration rate and a 4 times lower
      density of leaf for pea, which causes a 7 times higher foliar uptake in pea than
      in sugar beet. Low pH decreases the net uptake of Cd, probably by an exchange
      reaction in the cutin and pectin of the cuticular membrane. Stomata are not
      directly involved in the Cd uptake, and the differences in the sum total of
      stomatal aperture area per unit leaf area is not related to differences in foliar
      uptake of Cd. Percentage of open stomata, calculated as average of both sides of
      the leaves, was not affected by changes in pH: but especially at high pH.
      proportionally more stomata were open on the adaxial than on the abaxial side.

PMID- 28741770
TI  - Aluminum enhancement of plant growth in acid rooting media. A case of reciprocal
      alleviation of toxicity by two toxic cations.
AB  - The generally rhizotoxic ion Al3+ often enhances root growth at low
      concentrations. The hypothesis that Al3+ enhances growth by relieving H+ toxicity
      was tested with wheat seedlings (Triticum aestivum L.). Growth enhancement by
      Al3+ only occurred under acidic conditions that reduced root elongation. Al3+
      increased cell membrane electrical polarity and stimulated H+ extrusion. Previous
      investigations have shown that Al3+ decreases solute leakage at low p H and that
      the alleviation of H+ toxicity by cations appears to be a general phenomenon with
      effectiveness dependent upon charge (C3+ >C2+ >Cl+ ). Alleviation of one cation
      toxicity by another toxic cation appears to be reciprocal so that Al3+ toxicity
      is relieved by H+ . It has been argued previously that this latter phenomenon
      accounts for the apparent toxicity of ALOH2+ and Al(OH)+2 . Reduction of cell
      surface electrical potential by the ameliorative cation may reduce the cell
      surface activity of the toxic cation.

PMID- 28741771
TI  - A Cucumis sativus cell-free translation system: preparation, optimization and
      sensitivity to some antibiotics and ribosome inactivating proteins.
AB  - A cell-free translation system was prepared from 3- to 5-day-old embryonic axes
      of gherkin (Cucumis sativus L.). The system was optimized for Mg2+ , K+ , NH+4 ,
      high speed supernatants, tRNA mixture from wheat germ, time and temperature. The
      system translates efficiently both endogenous mRNA (using a 30000 g supernatant)
      and polyuridylic acid (using either a 30000 g supernatant or a 100000 g
      supernatant supplemented with purified ribosomes). Translation by gherkin
      ribosomes was inhibited by several well-known eukaryotic inhibitors, antibiotics
      and ribosome-inactivating proteins. A translational inhibitory activity found in
      Cucumis sativus L. dry seeds acted on polypeptide synthesis carried out by cell
      free systems from several mammals and plants, including gherkin embryonic axes.
      Our results indicate that the inhibitor is located in the seed bark and
      cotyledons, and is either blocked or absent in the embryonic axes, thus allowing
      the isolation of active gherkin ribosomes. The presence of the putative inhibitor
      appeared to be unevenly distributed in developing plants.

PMID- 28741772
TI  - Effect of nitrogen supply on frost resistance, nitrogen metabolism and
      carbohydrate content in white clover (Trifolium repens).
AB  - Effects of mineral nitrogen (2, 4, 6 and 8 mM NH4 NO3 ) and nodulation with
      Rhizobium on frost hardiness in seedlings of white clover (Trifolium repens) have
      been studied. Seedlings of a population from Bodo (67 degrees N lat.) were grown
      in Leonard jars under controlled conditions in a phytotron. For induction of
      frost hardening, plants were first exposed to 12 h photoperiod conditions for 2
      weeks at 18 degrees C, then for 2 weeks at 6 degrees C and finally for 2 weeks at
      0.5 degrees C. Frost hardiness after treatments at 6 and 0.5 degrees C was
      significantly enhanced by increasing nitrogen supply and was positively
      correlated with total nitrogen content of the stolons. Frost hardiness of
      nodulated plants correlated to the tissue nitrogen concentration. Content of
      soluble proteins in stolons decreased during hardening at 6 degrees C but did not
      change during treatment at 0.5 degrees C. There were minor changes in total
      amount of free amino acids during hardening. Both absolute and relative amounts
      of proline and arginine increased, and those of asparagine decreased during
      hardening. Absolute amounts of all free amino acids increased with increasing
      nitrogen supply, but the changes during hardening were similar in all treatments.
      There was a significant increase in the content of soluble carbohydrates during
      hardening. However, this increase was inversely related to nitrogen supply.

PMID- 28741773
TI  - TL -DNA transformation decreases ABA level.
AB  - The endogenous levels of ABA were measured in Agrobacterium rhizogenes A4 Tl -DNA
      transformed oilseed rape (Brassica napus L. var. oleifera cv. Brutor and cv.
      Drakkar), cabbage (Brassica oleracea). A4 transformed tobacco (Nicotiana tabacum
      cv. Xanthi) and their normal counterparts, using high performance liquid
      chromatography and enzyme-liked immunosorbent assay. Measurements were made on
      different plant tissues (i. e. floral stem, terminal bud, young leaf, mature
      leaf, root and root tips) and ABA levels were compared in unstressed and
      osmotically stressed oilseed rape plants (cv. Brutor). In unstressed Plants. in
      each of the 5 independent transformation events studied, a significant reduction
      (about 65% of control) in ABA concentration was observed in all transformed
      plants. When subjected to an osmotic stress, TL transformed Brutor plants showed
      a higher ABA accumulation than untransformed plants. The change in ABA content as
      a consequence of TL -DNA transformation is discussed with regard to phenotype,
      drought resistance and adaptability.

PMID- 28741774
TI  - Occurrence of hydroxylated jasmonic acids in leaflets of Solanum demissum plants
      grown under long- and short-day conditions.
AB  - Under short-day (SD) conditions both 11-OH-jasmonic acid (11-OH-JA) and a smaller
      quantity of 12-OH-JA occurred in leaflets of Solanum demissum Lindl. Plants which
      had formed tubers. This is the first time that 11-OH-JA has been detected as a
      native substance in higher plants. Under long-day (LD) conditions no tubers were
      formed and none of these compounds were detectable. A positive correlation was
      found between the occurrence of 11-OH-JA and 12-OH-JA in leaflets of S. demissum
      and tuber formation, but a causal relation has yet to be proved. The (-)-JA
      content in leaflets was not significantly different under short and long days.
      Mild stress applied to detached SD and LD leaflets caused a rapid accumulation of
      JA in these leaflets. Upon this treatment an increase in the levels of
      hydroxylated JAs was detected in SD leaflets only. JA was a potent promotor of
      tuber formation in vitro in S. demissum explants. Lipoxygenase (LOX: EC
      1.13.11.12) is involved in the biosynthesis of JA. Under SD conditions,
      application of salicylhydroxamic acid (SHAM), an inhibitor of LOX activity, to
      the roots did not prevent tuber formation in vivo. It is suggested that daylength
      controls the hydroxylation of JA. The enzyme(s), responsible for the
      hydroxylation of JA, would only be effective under SD conditions.

PMID- 28741775
TI  - ABA promotion of ethylene production in anther culture of Brussels sprouts
      (Brassica oleracea var. gemmifera) and its relevance to embryogenesis.
AB  - Abscisic acid (ABA) inhibited embryogenesis in anther culture of Brussels
      sprouts. This was accompanied by enhanced ethylene production during the first
      half of the anther culture period followed by a reduction in ethylene during the
      latter half, when compared to anthers not treated with ABA. The enhancement of
      ethylene production by ABA 6 h and 48 h after the start of the culture period was
      counteracted by the ethylene biosynthesis inhibitor aminoethoxyvinylglycine
      (AVG). Both AVG and the ethylene antagonist AgNO3 removed much of the ABA
      inhibition of embryogenesis, suggesting that at least part of the ABA effect on
      embryo production is mediated through increased ethylene biosynthesis. ABA
      promotion of ethylene production was reduced by high temperature: less ethylene
      evolved from ABA-treated anthers following a 24 h treatment at 35 degrees C than
      from ABA-treated anthers incubated continuously at 25 degrees C. A high
      temperature treatment such as this is invariably necessary for embryogenesis in
      Brussels sprouts anther culture.

PMID- 28741776
TI  - Effect of culture conditions on the isocitrate dehydrogenase and isocitrate lyase
      activities in Chlamydomonas reinhardtii.
AB  - In the green alga Chlamydomonas reinhardtii, nitrogen staravation induced a
      reversible increase (2-fold) in NAD-isocitrate dehydrogenase (NAD-IDH; EC
      1.1.1.41) and NADP-isocitrate dehydrogenase (NADP-IDH; EC 1.1.1.42) activities.
      Both enzymes were not affected by the concentration of CO2 , the dark or the
      nature of the nitrogen source (nitrate, nitrite, or ammonium). When cells growing
      autotrophically were transferred to heterotrophic conditions, a 40% reduction of
      the NAD-IDH activity was detected, a 2-fold increase of NADP-IDH was observed and
      isocitrate lyase (ICL; EC 4.1.3.1) activity was induced. The replacement of
      autotrophic conditions led to the initial activity levels. NAD- and NADP-IDH
      activities showed markedly different patterns of increase in synchronous cultures
      of this alga obtained by 12 h light/12 h dark transitions. While NAD-IDH
      increased in the last 4 h of the dark period, NADP-IDH increased during the last
      4 h of the light period, remaining constant for the rest of the cycle.

PMID- 28741777
TI  - Does the alternative pathway ameliorate chilling injury in sensitive plant
      tissues?
AB  - Free radical processes have been observed in senescence and several membrane
      associated disorders of plants including chilling, freezing, and desiccation
      injuries. The mitochondria of plant tissues exposed to low temperatures, and
      other abiotic and biotic stresses, produce superoxide and/or hydrogen peroxide
      when electron transport through the cytochrome pathway is impaired due to the
      energy state of the cell or to stress-induced physical changes in the membrane
      components. The superoxide and/or hydrogen peroxide produced can diffuse
      throughout the cell causing peroxidation of membrane lipids which results in
      membrane disruption, increased permeability and metabolic disturbances, and
      eventually the visible symptoms of chilling injury. The alternative pathway of
      electron transport in the mitochondria, which is induced by low temperatures in
      some plant tissues, can mediate these degradative processes by reducing the level
      of superoxide generated by the mitochondria.

PMID- 28741778
TI  - The enigmatic cytochrome b-559 of oxygenic photosynthesis.
AB  - The ubiquitous and obligatory association of cytochrome b-559 with the
      photosystem II reaction center of oxygenic photosynthesis is a conundrum since it
      seems not to have a function in the primary electron transport pathway of oxygen
      evolution. A model for the cytochrome structure that satisfies the cis-positive
      rule for membrane protein assembly consists of two short, non-identical
      hydrophobic membrane-spanning polypeptides (alpha and beta), each containing a
      single histidine residue, as ligands for the bridging heme prosthetic group that
      is on the side of the membrane opposite to the water splitting apparatus. The
      ability of the heterodimer, but not the single alpha-subunit, to satisfy the cis
      positive rule implies that the cytochrome inserts into the membrane as a
      heterodimer, with some evidence implicating it as the first membrane inserted
      unit of the assembling reaction center. The very positive redox potential of the
      cytochrome can be explained by a position for the heme in a hydrophobic niche
      near the stromal aqueous interface where it is also influenced by the large
      positive dipole potential of the parallel alpha-helices of the cytochrome. The
      requirement for the cytochrome in oxygenic photosynthesis may be a consequence of
      the presence of the strongly oxidizing reaction center needed for H2 O-splitting.
      This may lead to the need, under conditions of stress or plastid development, for
      an alternate source of electrons when the H2 O-splitting system is not operative
      as a source of reductant for the reaction center.

PMID- 28741779
TI  - Biochemical and physiological responses of Gracilaria tenuistipitata uuder two
      different nitrogen treatments.
AB  - The influence of nitrogen on ribulose-1.5-bisphosphate carboxylase/oxygenase
      (Rubisco. EC 4.1.1.39) content is poorly understood in macroalgae. N-deficient
      Gracilaria tenuistipitata Zhang et Xia var. liui was cultivated in the laboratory
      under constant light intensity and temperature. Biochemical and physiological
      variables were monitored after a high (1 mM) or low (o. 1 mM) nitrate pulse.
      Rubisco content in crude extracts was estimated by SDS-PAGE with the Coomassie
      Blue Staining procedure. Nitrate was consumed immediately in the low-N treatment,
      but there was always an external nitrate source in the high-N treatment. Total
      soluble proteins and phycobiliproteins decreased as internal nitrogen diminished
      in the low-N treatment, but kept fairly constant in N-sufficient conditions.
      However, Rubisco content increased until the 7th day and then started to decrease
      in both cases. Fresh weight increment showed a better correlation with Rubisco
      than with pigment content.

PMID- 28741780
TI  - Expression and occurrence of uracil-DNA glycosylase in higher plants.
AB  - Uracil-DNA glycosylase (UDG) is the first enzyme in the base excision repair
      pathway for removal of uracil in DNA. DNA repair capacity is likely to be a
      critical factor in mutagenesis and thereby in the capacity to prevent genetic
      damage and unwanted variation. We have studied expression of UDG in 9 higher
      plant species. The highest expression of UDG was measured in Solanum tuberosum. A
      comparison of 6 Solanum tuberosum cultivars showed that the specific activity
      ranged from 30 pmol mg1 protein min-1 in the cultivar Laila to 80 pmol mg-1
      protein min-1 in the cultivar Ostara. Measurement of UDG in Begonia X cheimantha
      gave no indications of enzyme activity. The possible effects of no or low UDG
      activity is discussed. In vitro cultures of Solanum tuberosum and Thymus vulgaris
      were used to examine the effect of auxin and cytokinin on the UDG activity.
      Axillary shoots of Solanum tuberosum were cultured on medium including 20
      variations in hormone concentration. Auxin (1-naphtaleneacetic acid) increased
      the expression of UDG. Plants cultured on medium supplemented with 3 mg 1-1 1
      naphtaleneacetic acid showed a specific UDG activity which was approximately 3
      fold higher than the activity in controls. The cytokinin benzyladenine reduced
      the specific UDG activity at concentrations in the range 0.25-10 mg 1-1 . In
      vitro cultured Saintpaulia ionantha was used to examine UDG activity during
      initiation, conditioning and multiplication cycles. In general, highest
      expression of UDG was measured in the conditioning cycle on hormone free medium.
      Measurement of UDG expression during single subculture periods, clearly showed
      that UDG expression may vary over one culture period. Expression of UDG was in
      general highest three weeks after transfer to fresh medium. Of different seedling
      organs from 0- to 15-day-old Brassica napus L., roots and hypocotyls showed the
      highest UDG activities. In cotyledons a very low and nearly constant specific
      activity was observed. In 12-day-old seedlings the activity in roots was
      approximately 20 times higher than the activity in cotyledons.

PMID- 28741781
TI  - Preferential photoinactivation of catalase and photoinhibition of photosystem II
      are common early symptoms under various osmotic and chemical stress conditions.
AB  - Activity of catalase (EC 1.11.1.6) and variable fluorescence (F) were measured in
      sections of rye leaves (Secale cereale L. cv. Halo) that were exposed for 24 h to
      moderately high irradiance under osmotic or chemical stress conditions (paraquat,
      DCMU, mannitol, NaCl, CdCl2 , CuSO4 , Pb(NO3 )2 , KNO2 , or K2 SO3 ). Changes of
      the chlorophyll content and of enzyme activities related to peroxide metabolism,
      such as glycolate oxidase, glutathione reductase, and peroxidase, were assayed
      for comparison. In the presence of the herbicides paraquat and low DCMU
      concentrations that exert only partial inhibition of photosynthesis, as well as
      after most treatments with osmotic or chemical stress factors, catalase markedly
      declined due to a preferential photoinactivation. At higher DCMU levels catalase
      did not decline. At low KNO2 concentrations catalase activity was preferentially
      increased. In general, photoinactivation of catalase was accompanied by a decline
      of the F/Fm ratio, indicating photoinhibition of photosystem II, while other
      parameters were much more stable. Inasmuch as both catalase and the D1 reaction
      center protein of photosystem II have a rapid turnover in light, their steady
      state levels appear to decline whenever stress effects either excessively enhance
      deleterious oxidative conditions and degradation (e. g. Paraquat, low DCMU), or
      inhibit repair synthesis. Photoinactivation of catalase and of photosystem II
      represent specific and widely occurring early symptoms of incipient photodamage
      indicating stress conditions where the repair capacity is not sufficient. During
      prolonged exposures, e. g. to NaCl and CuSO4 , chlorophyll was bleached in light
      and the rate of its photodegradation increased in proportion as the catalase
      level had declined. The results suggest that the enhanced susceptibility of leaf
      tissues to photooxidative damage which is widely observed in stressed plants is
      related to the early loss of catalase.

PMID- 28741782
TI  - Elicitation of H2 O2 production in cucumber hypocotyl segments by oligo-1,4-alpha
      D-galacturonides and an oligo-beta-glucan preparation from cell walls of
      Phythophthora megasperma f. sp. glycinea.
AB  - The production of H2 O2 by cucumber hypocotyl segments (Cucumis sativus L. cv.
      Wisconsin SMR 58) in response to alpha-1,4-linked oligomers of galacturonic acid
      and oligo-beta-glucans from the cell walls of Phytophthora megasperma f. sp.
      glycinea was studied. Oligogalacturonides with degrees of polymerization of 9 to
      13 elicited H2 O2 production, the most effective being the deca-, undeca- and
      dodecamers. A similar relationship between size and effect was previously
      obtained when oligogalacturonides were tested for their ability to elicit
      lignification in cucumber hypocotyls. The oligogalacturonide-induced increase in
      H2 O2 concentration was detected after 4 h, reaching a maximum after 10 h of
      incubation. The glucan elicitor induced lignification at a 100-fold lower
      concentration than the oligogalacturonides, but yielded only 10% of the maximum
      H2 O2 accumulation seen with oligogalacturonides. The glucan elicitor-induced H2
      O2 production was detectable after 2 h, and reached a maximum after 4 to 6 h.
      Catalase abolished the elicitation of both phenol red oxidation and lignification
      in cucumber hypocotyls. At least part of the oligogalacturonide-induced H2 O2
      production appeared to be dependent upon de novo protein synthesis.

PMID- 28741783
TI  - Abscisic acid and assimilate partitioning to developing seeds. II. Does abscisic
      acid influence the sink strength of Arabidopsis seeds?
AB  - The role of abscisic acid (ABA) in the regulation of transport of assimilates to
      seeds was investigated with the aid of Arabidopsis thaliana mutants that were ABA
      deficient and/or insensitive to ABA. Subsequent flowers of mutant mother plants
      were alternately pollinated with pollen from either wild-type or mutant plants,
      and the transport of radiolabelled photoassimilates to the genetically different
      seeds was studied. The experiments were performed under conditions of reduced
      availability of source material, achieved either by reduced light quantity or by
      combining the ABA-deficient mutant with a starchless mutant. No effect of the
      genotype on the import rate of assimilates was detected, indicating that
      endogenous ABA does not influence the sink strength of Arabidopsis seeds. Reports
      describing contrary results are discussed.

PMID- 28741784
TI  - Incorporation of 15 N and 14 C of methionine into the mugineic acid family of
      phytosiderophores in iron-deficient barley roots.
AB  - The role of methionine as a precursor in mugineic acid (MA) biosynthesis was
      studied by feeding 15 N-ammonium sulfate, 14 C-amino acids, and [1-14 C, 15 N]
      methionine to iron-deficient barley roots (Hordeum vulgare L. cv. Minorimugi),
      grown hydroponically. The incorporation of isotopes into amino acids was also
      examined. Methionine appears to be the most efficient precursor of the mugineic
      acid family (MAs) of phytosiderophores; homoserine was also incorporated into the
      MAs, but other amino acids such as glutamate, alanine, and gamma-amino butyric
      acid did not act as precursors of MAs. Carbon-14 and 15 N of methionine were
      incorporated into MAs. This specific incorporation of 14 C and 15 N indicated
      that the nitrogen atoms of MAs were derived from two molecules of methionine. It
      is suggested that deoxymugineic acid (DMA) is probably the first phytosiderophore
      to be synthesized on the biosynthetic pathway of MAs.

PMID- 28741785
TI  - ASPRE trial: performance of screening for preterm pre-eclampsia.
AB  - OBJECTIVE: To examine the performance of screening for preterm and term pre
      eclampsia (PE) in the study population participating in the ASPRE (Combined
      Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence
      Based Preeclampsia Prevention) trial. METHODS: This was a prospective first
      trimester multicenter study on screening for preterm PE in 26 941 singleton
      pregnancies by means of an algorithm that combines maternal factors, mean
      arterial pressure, uterine artery pulsatility index and maternal serum pregnancy
      associated plasma protein-A and placental growth factor at 11-13 weeks'
      gestation. Eligible women with an estimated risk for preterm PE of > 1 in 100
      were invited to participate in a double-blind trial of aspirin (150 mg per day)
      vs placebo from 11-14 until 36 weeks' gestation, which showed that, in the
      aspirin group, the incidence of preterm PE was reduced by 62%. In the screened
      population, the detection rates (DRs) and false-positive rates (FPRs) for
      delivery with PE < 37 and >= 37 weeks were estimated after adjustment for the
      effect of aspirin in those receiving this treatment. We excluded 1144 (4.2%)
      pregnancies because of loss to follow-up or study withdrawal (n = 716),
      miscarriage (n = 243) or termination (n = 185). RESULTS: The study population of
      25 797 pregnancies included 180 (0.7%) cases of preterm PE, 450 (1.7%) of term PE
      and 25 167 (97.6%) without PE. In combined first-trimester screening for preterm
      PE with a risk cut-off of 1 in 100, the DR was 76.7% (138/180) for preterm PE and
      43.1% (194/450) for term PE, at screen-positive rate of 10.5% (2707/25 797) and
      FPR of 9.2% (2375/25 797). CONCLUSION: The performance of screening in the ASPRE
      study was comparable with that of a study of approximately 60 000 singleton
      pregnancies used for development of the algorithm; in that study, combined
      screening detected 76.6% of cases of preterm PE and 38.3% of term PE at a FPR of
      10%. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28741787
TI  - Advances in Stereoselective 1,2-cis Glycosylation using C-2 Auxiliaries.
AB  - The control of stereoselectivity in a glycosylation reaction remains one of the
      most challenging aspects of oligosaccharide synthesis. Especially the synthesis
      of 1,2-cis-glycosides is challenging and generally applicable methodology to
      prepare this linkage is needed to standardize oligosaccharide synthesis. This
      review highlights the recent development of an elegant strategy employing a C-2
      auxiliary to control the anomeric stereoselectivity in glycosylations. The
      various auxiliaries developed to date, their compatibility with protecting groups
      and monosaccharide types as well as mechanistic aspects are summarized.
      Furthermore, the application, advantages and limitations of C-2 auxiliaries in
      oligosaccharide synthesis are discussed.

PMID- 28741786
TI  - Ectopic parathyroid adenoma in the pyriform sinus.
AB  - BACKGROUND: Ectopic parathyroid glands may complicate the surgical approach to
      primary hyperparathyroidism. We describe a rare ectopic parathyroid location, the
      pyriform sinus. METHODS: Three patients, 2 after prior unsuccessful parathyroid
      exploration, were found to have ectopic parathyroid adenomas in the pyriform
      sinus. Two cases were identified by 4D-CT of the neck. The other was localized by
      a technetium 99m sestamibi single photon emission CT (SPECT). In each case,
      office endoscopy confirmed the lesions. The patients were treated by either
      transoral laser or robotic resection of the parathyroid adenoma. RESULTS: After
      surgery, the patients had resolution of their hyperparathyroidism. CONCLUSION:
      Ectopic parathyroid adenomas in the pyriform sinus are rare, but should be
      considered in those patients who have had a failed neck exploration and in those
      who undergo 4D-CT scanning or SPECT scanning.

PMID- 28741789
TI  - Screening of curcumin-derived isoxazole, pyrazoles, and pyrimidines for their
      anti-inflammatory, antinociceptive, and cyclooxygenase-2 inhibition.
AB  - Curcumin has shown pharmacological properties against different phenotypes of
      various disease models. Different synthetic routes have been employed to develop
      its numerous derivatives for diverse and improved therapeutic roles. In this
      study, we have synthesized curcumin derivatives containing isoxazole, pyrazoles,
      and pyrimidines and then the synthesized molecules were evaluated for their anti
      inflammatory and antinociceptive activities in experimental animal models. Acute
      toxicity of synthesized molecules was evaluated in albino mice by oral
      administration. Any behavioral and neurological changes were observed at dose of
      10 mg/kg body weight. Additionally, cyclooxygenase-2 (COX-2) enzyme inhibition
      studies were performed through in vitro assays. In vivo anti-inflammatory studies
      showed that curcumin with pyrimidines was the most potent anti-inflammatory agent
      which inhibited induced edema from 74.7% to 75.9%. Compounds 7, 9, and 12
      exhibited relatively higher prevention of writhing episodes than any other
      compound with antinociceptive activity of 73.2%, 74.9%, and 71.8%, respectively.
      This was better than diclofenac sodium (reference drug, 67.1% inhibition).
      Similarly, COX-2 in vitro inhibition assays results revealed that compound 12
      (75.3% inhibition) was the most potent compound. Molecular docking studies of 10,
      11, and 12 compounds in human COX-2 binding site revealed the similar binding
      modes as that of other COX-2-selective inhibitors.

PMID- 28741788
TI  - Molecular analysis of single circulating tumour cells following long-term storage
      of clinical samples.
AB  - The CellSearch(r) semiautomated CTC enrichment and staining system has been
      established as the 'gold standard' for CTC enumeration with CellSearch(r) CTC
      counts recognized by the FDA as prognostic for a number of cancers. We and others
      have gone on to show that molecular analysis of CellSearch(r) CTCs isolated
      shortly after CellSearch(r) enrichment provides another valuable layer of
      information that has potential clinical utility including predicting response to
      treatment. Although CellSearch(r) CTCs can be readily isolated after enrichment,
      the process of analysing a single CellSearch(r) patient sample, which may contain
      many CTCs, is both time-consuming and costly. Here, we describe a simple process
      that will allow storage of all CellSearch(r) -enriched cells in glycerol at -20 
      degrees C for up to 2 years without any measurable loss in the ability to
      retrieve single cells or in the genome integrity of the isolated cells. To
      establish the suitability of long-term glycerol storage for single-cell molecular
      analysis, we isolated individual CellSearch(r) -enriched cells by DEPArrayTM
      either shortly after CellSearch(r) enrichment or following storage of matched
      enriched cells in glycerol at -20  degrees C. All isolated cells were subjected
      to whole-genome amplification (WGA), and the efficacy of single-cell WGA was
      evaluated by multiplex PCR to generate a Genome Integrity Index (GII). The GII
      results from 409 single cells obtained from both 'spike-in' controls and clinical
      samples showed no statistical difference between values obtained pre- and
      postglycerol storage and that there is no further loss in integrity when
      DEPArrayTM-isolated cells are then stored at -80  degrees C for up to 2 years. In
      summary, we have established simple yet effective 'stop-off' points along the CTC
      workflow enabling CTC banking and facilitating selection of suitable samples for
      intensive analysis once patient outcomes are known.

PMID- 28741790
TI  - Diallyl trisulfide inhibits cell migration and invasion of human melanoma a375
      cells via inhibiting integrin/facal adhesion kinase pathway.
AB  - Melanoma is the leading cause of death from skin disease due to its propensity
      for metastasis. Studies have shown that integrin-mediated focal adhesion kinase
      (FAK) signal pathway is implicated in cell proliferation, survival and metastasis
      of tumor cells. Our previous results indicated that diallyl trisulfide (DATS)
      provided its antimelanoma activity via inducing cell cycle arrest and apoptosis.
      The aim of this study was to explore DATS mediated antimetastatic effect and the
      corresponding mechanism in human melanoma A375 cells. We found that DATS
      exhibited an inhibitory effect on the abilities of migration and invasion in A375
      cells under noncytotoxic concentrations analyzed by wound healing assays and
      Matrigel invasion chamber system. DATS attenuated invasion of A375 cells with
      characteristic of decreased activities and protein expressions of matrix
      metalloproteinase-2 (MMP-2) and MMP-9. Moreover, DATS exerted an inhibitory
      effect on cell adhesion of A375 cells, which is in correlation with the change in
      integrin signaling pathway. Results of Western blotting showed that DATS
      decreased the levels of several integrin subunits, including alpha4, alpha5,
      alphav, beta1, beta3 and beta4. Subsequently, DATS induced a strong decrease in
      total FAK, phosphorylated FAK Tyr-397,-576, -577, and disorganized F-actin stress
      fibers, resulting in a nonmigratory phenotype. These results suggest that the
      antimetastatic potential of DATS for human melanoma cells might be due to the
      disruption of integrin/FAK signaling pathway.

PMID- 28741791
TI  - Comparison of the Safety and Effectiveness of Apixaban versus Warfarin in
      Patients with Severe Renal Impairment: An Alternative Viewpoint.

PMID- 28741792
TI  - Bilateral lesions of the paraventricular hypothalamic nucleus disrupt nursing
      behavior in rabbits.
AB  - Doe rabbits nurse the litter only once a day, for around 3 min, with circa 24-h
      periodicity. To explore the participation of the paraventricular nucleus (PVN) in
      regulating this behavior, we lesioned it bilaterally with kainic acid on
      lactation day 7. Bilateral lesions, comprising less than 50% of the total PVN
      volume, abolished nursing behavior (4/8 does) or severely disrupted its normal
      periodicity (4/8 does). In the latter case, duration of nursing bouts was normal.
      Body weight, food and water intake were not significantly affected by bilateral
      PVN lesions. Unilateral lesions of the PVN or lesions located outside this
      nucleus did not significantly alter nursing periodicity or any other behavioral
      parameter. Results indicate an important role of the PVN for (i) maintaining
      maternal behavior, and (ii) the periodic display of nursing across lactation in
      rabbits.

PMID- 28741793
TI  - Telomerase enzyme deficiency promotes metabolic dysfunction in murine hepatocytes
      upon dietary stress.
AB  - BACKGROUND & AIMS: Short telomeres and genetic telomerase defects are risk
      factors for some human liver diseases, ranging from non-alcoholic fatty liver
      disease and non-alcoholic steatohepatitis to cirrhosis. In murine models,
      telomere dysfunction has been shown to metabolically compromise hematopoietic
      cells, liver and heart via the activation of the p53-PGC axis. METHODS: Tert- and
      Terc-deficient mice were challenged with liquid high-fat diet. Liver metabolic
      contents were analysed by CE-TOFMS and liver fat content was confirmed by
      confocal and electronic microscopy. RESULTS: Tert-deficient but not Terc
      deficient mice develop hepatocyte injury and frank steatosis when challenged with
      liquid high-fat diet. Upon high-fat diet, Tert-/- hepatocytes fail to engage the
      citric acid cycle (TCA), with an imbalance of NADPH/NADP+ and NADH/NAD+ ratios
      and depletion of intermediates of TCA cycle, such as cis-aconitic acid.
      Telomerase deficiency caused an intrinsic metabolic defect unresponsive to
      environmental challenge. Chemical inhibition of telomerase by zidovudine
      recapitulated the abnormal Tert-/- metabolic phenotype in Terc-/- hepatocytes.
      CONCLUSIONS: Our findings indicate that in telomeropathies short telomeres are
      not the only molecular trigger and telomerase enzyme deficiency provokes
      hepatocyte metabolic dysfunction, abrogates response to environmental challenge,
      and causes cellular injury and steatosis, providing a mechanism for liver damage
      in telomere diseases.

PMID- 28741794
TI  - Ecological segregation moderates a climactic conclusion to trout hybridization.
AB  - For decades, it has been assumed that introgressive hybridization between
      introduced rainbow trout and native cutthroat trout in western North America will
      lead to genomic extinction of the latter. A broad-scale re-examination of their
      interaction indicates that ecological differences between these species and
      demographic processes are dictating the location and extent of their hybrid
      zones, and that runaway introgression between these taxa is unlikely.

PMID- 28741795
TI  - Novel molecular mechanism of cellular transformation by a mutant molecular
      chaperone in myeloproliferative neoplasms.
AB  - Deregulation of the cytokine-receptor signaling pathway plays a significant role
      in tumorigenesis. Such deregulation is frequently caused by alterations in the
      genes involved in the signaling pathway. At the end of 2013, recurrent somatic
      mutations in the calreticulin (CALR) gene that encodes a molecular chaperone were
      identified in a subset of patients with Philadelphia-chromosome negative
      myeloproliferative neoplasms (MPN). The present review focuses on the role of
      CALR mutations in the oncogenic transformations observed in MPN. All the CALR
      mutations were found to generate a + 1 frameshift in the reading frame on exon 9,
      which encodes the carboxy (C)-terminus end of CALR, and thus conferred a common
      mutant-specific sequence in all the CALR mutants. The mutant CALR (but not the
      wild-type) constitutively activates the thrombopoietin (TPO) receptor,
      myeloproliferative leukemia protein (MPL), even in the absence of TPO to induce
      cellular transformation. Preferential interaction between the mutant CALR and MPL
      is achieved by a presumptive conformational change induced by the mutant-specific
      C-terminus domain, which allows N-domain binding to MPL. Even though mutant CALR
      is expressed on the cell surface and is secreted out of cells, it only presents
      autocrine capacity for MPL activation. These findings define a novel molecular
      mechanism by which the mutant molecular chaperone constitutively activates the
      cytokine receptor to induce cellular transformation.

PMID- 28741796
TI  - Effectiveness of applying flipped learning to clinical nursing practicums for
      nursing students in Korea: A randomized controlled trial.
AB  - OBJECTIVES: The purpose of this study was to develop flipped learning models for
      clinical practicums and compare their effectiveness regarding learner motivation
      toward learning, satisfaction, and confidence in performing core nursing skills
      among undergraduate nursing students in Korea. METHODS: This study was a
      randomized clinical trial designed to compare the effectiveness of 2 flipped
      learning models. Data were collected for 3 days from October 21 to 23, 2015
      before the clinical practicum was implemented and for 2 weeks from October 26 to
      December 18, 2015 during the practicum period. RESULTS: The confidence of the
      students in performing core nursing skills was likely to increase after they
      engaged in the clinical practicum in both study groups. However, while learner
      confidence and motivation were not affected by the type of flipped learning,
      learner satisfaction did differ between the 2 groups. CONCLUSIONS: The findings
      indicate that applying flipped learning allows students to conduct individualized
      learning with a diversity of clinical cases at their own level of understanding
      and at their own pace before they participate in real-world practicums.

PMID- 28741797
TI  - Risk factors and long-term outcomes of parvovirus B19 infection in kidney
      transplant patients.
AB  - BACKGROUND: Parvovirus B19 is a small, non-enveloped, single-stranded DNA virus
      with a special affinity for the erythroid progenitor cells of the bone marrow.
      The first case of parvovirus B19 infection in a kidney transplant recipient (KTR)
      was reported in 1986. Data on the risk factors and specific clinical
      characteristics of parvovirus B19 infection remain insufficient. METHODS: We
      screened 602 KTRs for parvovirus B19 infection using parvovirus B19 polymerase
      chain reaction (PCR) from January 1990 to April 2016, and the clinical
      characteristics of patients with positive results were compared to those of age-
      and gender-matched patients with negative PCR results. RESULTS: A total of 39
      KTRs tested positive for parvovirus B19, and they were compared to 78 age- and
      gender-matched patients among 563 KTRs who had negative PCR results. In all,
      89.7% of positive cases were reported within the first year after kidney
      transplantation. In multivariate analyses, deceased-donor kidney transplantation
      (odds ratio [OR] 9.067, 95% confidence interval [CI] 1.668-49.275, P = .011), use
      of tacrolimus (OR 3.607, 95% CI 1.024-12.706, P = .046), PCR test within 1 year
      of kidney transplantation (OR 12.456, 95% CI 2.674-58.036, P = .001), and
      hemoglobin levels (OR 0.559, 95% CI 0.351-0.889, P = .014) showed significant
      correlations with parvovirus B19 infection. Graft survival did not differ between
      the two groups during the follow-up period of 111.68 +/- 54.54 months (P = .685
      by log-rank test). CONCLUSION: The identification of factors related to positive
      parvovirus B19 PCR results may promote the early detection of parvovirus B19
      infection. Further studies are needed to elucidate the characteristics of
      parvovirus B19 infection in kidney transplantation.

PMID- 28741799
TI  - Multicenter study for brain/body hypothermia for hypoxic-ischemic encephalopathy:
      Changes in HMGB-1.
AB  - BACKGROUND: We measured changes in the blood level of high-mobility group box-1
      (HMGB-1) at 24 h intervals in neonates treated with brain/body hypothermia (body
      hypothermia therapy: BHT) for hypoxic-ischemic encephalopathy (HIE), to evaluate
      the usefulness of HMGB-1 level for determining outcomes. METHODS: We studied 15
      neonates with HIE who underwent BHT (BHT (+) group) and six neonates with HIE who
      did not (BHT (-) group). We recorded HMGB-1 changes at 24 h intervals, creatinine
      phosphokinase, and the resistance index of the anterior cerebral artery. Magnetic
      resonance imaging (MRI) was used to determine short-term outcome. RESULT:
      Baseline HMGB-1 was significantly higher in the BHT (+) group than in the BHT (-)
      group. Thereafter, HMGB-1 in the BHT (+) group significantly decreased at 24 h
      intervals, reaching the reference range by 2 days of age. In the BHT (+) group,
      when patients were classified into clinically significant neurological disorder
      due to HIE (+) and (-) according to MRI, the neurological disorder (+) group had
      higher mean HMGB-1. CONCLUSIONS: In HIE, HMGB-1 differs according to the presence
      of BHT, suggesting that HMGB-1 measurement soon after birth might be useful for
      determining BHT necessity and short-term outcome.

PMID- 28741798
TI  - Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy
      than an EZH2 selective inhibitor.
AB  - Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and
      represses gene expression to regulate cell proliferation and differentiation.
      Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a
      catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2
      or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some
      subunits of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling
      complexes have been observed. However, little is known about the function of EZH1
      in tumorigenesis. Herein, we developed novel, orally bioavailable EZH1/2 dual
      inhibitors that strongly and selectively inhibited methyltransferase activity of
      both EZH2 and EZH1. EZH1/2 dual inhibitors suppressed trimethylation of histone
      H3 lysine 27 in cells more than EZH2 selective inhibitors. They also showed
      greater antitumor efficacy than EZH2 selective inhibitor in vitro and in vivo
      against diffuse large B-cell lymphoma cells harboring gain-of-function mutation
      in EZH2. A hematological cancer panel assay indicated that EZH1/2 dual inhibitor
      has efficacy against some lymphomas, multiple myeloma, and leukemia with fusion
      genes such as MLL-AF9, MLL-AF4, and AML1-ETO. A solid cancer panel assay
      demonstrated that some cancer cell lines are sensitive to EZH1/2 dual inhibitor
      in vitro and in vivo. No clear correlation was detected between sensitivity to
      EZH1/2 dual inhibitor and SWI/SNF mutations, with a few exceptions. Severe
      toxicity was not seen in rats treated with EZH1/2 dual inhibitor for 14 days at
      drug levels higher than those used in the antitumor study. Our results indicate
      the possibility of EZH1/2 dual inhibitors for clinical applications.

PMID- 28741800
TI  - Eteplirsen for the Treatment of Duchenne Muscular Dystrophy: Quality of Evidence
      Concerns-an Alternative Viewpoint.

PMID- 28741801
TI  - Attitudes towards suicidal behaviour and associated factors among nursing
      professionals: A quantitative study.
AB  - : WHAT IS KNOWN ON THE SUBJECT?: Self-confident health professionals with
      positive and understanding attitudes can take better care of people with suicidal
      behaviour, but the factors associated with these attitudes are not known. WHAT
      THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The majority of nursing professionals had
      no experience or training in mental health or suicide. They were less self
      confident and had more negative attitudes. Nurses and nursing assistants who
      worked before in mental health services were more understanding with people with
      suicidal behaviour. Nurses and nursing assistants who were working in prehospital
      services were less self-confident to taking care of people with suicidal
      behaviour. Some members of the nursing team had already seriously considered
      committing suicide. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The practicing,
      support and training in mental health may improve the nurses' attitudes and
      emotional competencies. It is important to know why few nurses had suicide
      related training, despite the relevance of this issue. Training in mental health
      or suicide need to include attitudinal and emotional competencies. It is
      important to offer emotional support to emergency nursing professionals.
      ABSTRACT: Background The attitudes towards suicide of emergency nurses may affect
      the care provided. However, the factors associated with these attitudes remain
      unclear. Objective To investigate attitudes towards suicidal behaviour and
      associated factors among nursing professionals working in emergency settings.
      Methods A cross-sectional observational study including 28 nurses and 118 who
      were nursing assistants employed at two emergency services in Brazil was
      conducted. Data were collected in 2015 using a self-administered sociodemographic
      questionnaire and the Suicide Behavior Attitude Questionnaire (SBAQ). Results The
      majority of participants reported having no experience or training in mental
      health or suicide. They reported more negative feelings towards the patient and a
      lower self-perception of professional competence regarding suicidal behaviours,
      and these attitudes seemed to reinforce each other. Nurses who worked in mental
      health services reported less moralistic/judgemental attitudes. Working in
      prehospital services was associated with having a lower self-perception of
      professional competence. There were professionals who reported thinking seriously
      about committing suicide. Conclusion When combined with support and training,
      practicing mental health nursing may serve as an opportunity to develop
      favourable attitudes and emotional competences, and these issues need to be
      addressed in suicide education strategies.

PMID- 28741802
TI  - Cytogenetic tests for animal production: state of the art and perspectives.
AB  - Cytogenetic tests are effective tools for monitoring the health status of
      livestock and improving their genetic value. Cytogenetic screening allows for the
      detection of animals carrying chromosomal aberrations and to avoid using them as
      breeders. Progress in karyotype monitoring, with new molecular probes and
      automation, has greatly increased the productivity of this procedure. Several
      genotoxicity tests are available to detect the possible presence and effects of
      pollutants or drugs. Among these, the micronucleus test and the Comet assay are
      the most convenient in terms of costs and benefits. Finally, analysis of
      telomeres, the end of chromosomes and markers of genomic instability, may be
      developed into a new marker of stress and genetic value.

PMID- 28741803
TI  - Delayed and localized Sweets syndrome after breast cancer radiotherapy.

PMID- 28741804
TI  - Does Whey Protein Supplementation Improve the Nutritional Status in
      Hypoalbuminemic Peritoneal Dialysis Patients?
AB  - Limited data are available regarding the effects of whey protein on the
      nutritional status of the peritoneal dialysis population. This study evaluated
      the effects of whey protein supplementation for 12 weeks on the nutritional
      status in hypoalbuminemic peritoneal dialysis patients. Thirty-six stable adult
      patients on maintenance peritoneal dialysis with serum albumin levels <3.5 g/dL
      were enrolled in the study and were divided into two groups similar in their
      serum albumin and normalized protein equivalent of total nitrogen appearance
      (nPNA). Nineteen patients were instructed to receive 1.2 g/kg per day of protein
      diet and additional whey protein supplement at a dose of 25% of the instructed
      daily protein diet (whey protein group), and 17 patients were instructed to
      receive 1.2 g/kg per day protein diet without additional whey protein
      supplementation (control group). Nutritional status was assessed using two
      measures: nPNA and lean tissue mass index (LTI) obtained by whole-body
      bioimpedance spectroscopy technique. In the whey protein group serum albumin and
      nPNA significantly increased from baseline to week 6 (P < 0.001, P = 0.034;
      respectively) and from week 6 to week 12 (P < 0.001, P = 0.001; respectively);
      LTI significantly increased from week 6 to week 12 (P = 0.022). Compared to the
      control group at week 12, serum albumin, nPNA and LTI values were significantly
      higher in the whey protein group (P < 0.001, P = 0.002, P = 0.001; respectively).
      This study demonstrated for the first time that oral supplementation with whey
      protein improves nutritional status and is well tolerated in hypoalbuminemic PD
      patients.

PMID- 28741805
TI  - Magnetic noninvasive acupuncture for infant comfort (MAGNIFIC) - a single-blinded
      randomised controlled pilot trial.
AB  - AIM: To determine the safety and feasibility of auricular noninvasive magnetic
      acupuncture (MA) to decrease infant pain during heel pricks. METHODS: Infants
      requiring heel pricks for blood collection were randomised to either MA (n = 21)
      or placebo (P) (n = 19) after parental informed consent. MA or placebo stickers
      were placed on both ears according to the Battlefield Protocol by an unblinded
      investigator and left on for 3 days. Pain was assessed with the Premature Infant
      Pain Profile (PIPP) by blinded clinicians. RESULTS: Mean gestation (MA:34.1,
      P:34.4 weeks) and age of infants (MA:5.3, P:4.5 days) were similar as were mean
      (SD) pre (MA:1.7(1.4), P:2.1(1.9)) and post (MA:1.6(1.4), P: 2.1(1.7)) heel prick
      PIPP scores. PIPP scores were significantly lower in MA infants during heel
      pricks (MA:5.9(3.7), P: 8.3(4.7), p = 0.04). One-way ANCOVA modelling showed that
      MA was significantly associated with lower PIPP scores after controlling for
      analgesic use (p = 0.043). No differences in heart rate, oxygen saturation,
      analgesic use or adverse effects (e.g. local skin reactions) noted. CONCLUSION:
      This pilot study shows that auricular MA is feasible in neonates and may reduce
      PIPP scores during heel pricks. Further study is required to determine the impact
      of MA on other painful or stressful conditions and on neurodevelopment.

PMID- 28741806
TI  - Serum gamma-glutamyltransferase level and metabolic syndrome in children and
      adolescents: Korean National Health and Nutrition Examination Survey.
AB  - AIMS/INTRODUCTION: Serum gamma-glutamyltransferase (GGT) is positively related to
      cardiometabolic diseases, such as type 2 diabetes mellitus, hypertension and
      metabolic syndrome (MetS), in adult populations. Our aim was to investigate
      whether serum GGT is independently associated with MetS and its components in a
      nationally representative sample of Korean children and adolescents. MATERIALS
      AND METHODS: The study included data from 1,618 participants (867 boys, 751
      girls) aged 10-18 years from the 2010-2011 Korean National Health and Nutrition
      Examination Survey. MetS was diagnosed by the 2007 International Diabetes
      Federation criteria for children and adolescents. Participants were stratified
      using a cut-off value of the 75th percentile of serum GGT levels (19 IU/L for
      boys, 15 IU/L for girls). The odds ratios and 95% confidence intervals for MetS
      and its components were determined with multiple logistic regression analyses.
      RESULTS: The mean values of most cardiometabolic variables were significantly
      higher in the upper stratum. Except for low high-density lipoprotein cholesterol
      in boys and elevated blood pressure in girls, participants in the upper GGT
      stratum had significantly higher odds of MetS and its components than those in
      the lower stratum. The multivariate-adjusted odds ratios for MetS for the upper
      stratum were 5.79 (95% confidence interval 1.21-27.02) in boys and 6.20 (95%
      confidence interval 1.71-22.47) in girls, after adjusting for age, household
      income and residential area. CONCLUSIONS: Serum GGT was positively associated
      with MetS and its components in Korean children and adolescents. Serum GGT could
      be a useful measure for identifying children and adolescents with MetS.

PMID- 28741807
TI  - IL17A polymorphism and elevated IL17A serum levels are associated with oral
      lichen planus.
AB  - OBJECTIVE: The aim of this study was to evaluate the association of IL17A G197A
      polymorphism and serum levels with oral lichen planus (OLP) susceptibility and
      clinical presentation. SUBJECTS AND METHODS: Eighty-three individuals diagnosed
      with OLP and 99 healthy controls (C) were consecutively recruited. All
      participants had desquamating oral mucosal cells collected and DNA isolated for
      IL17A (G197A) genotyping. Blood samples of 42 OLP individuals and 23 healthy
      controls were collected for evaluation of IL17A serum levels. RESULTS: IL17A
      G197A genotypes were associated with an increased chance of having OLP (GA/AA *
      GG, OR = 3.44, 95% CI = 1.87-6.33, p < .001). Overall A carriers (GA or AA) were
      more common in OLP (38.1%) than in C (20.2%; OR = 2.43, 95% CI = 1.53-3.87, p <
      .001). Serum levels of IL17A were higher among patients with OLP than in healthy
      controls (reticular, p = .0003; erosive, p < .001), but no difference was found
      among the disease types. CONCLUSIONS: IL17A G197A is associated with a higher
      susceptibility of developing OLP and these patients seem to present a
      considerable increase in IL17A serum levels. These findings suggest that Th17
      cells, and IL17A in particular, may play a pivotal role in OLP pathogenesis.

PMID- 28741808
TI  - Reconciling disparate data to determine the right answer: A grounded theory of
      meta analysts' reasoning in meta-analysis.
AB  - While the systematic review process is intended to maximize objectivity and limit
      researchers' biases, examples remain of discordant recommendations from meta
      analyses. Current guidelines to explore discrepancies assume the variation is
      produced by methodological differences and thus focus only on the study process.
      Because heterogeneity of interpretation also occurs when experts examine the same
      data, our purpose was to examine if there are reasoning differences, ie, in how
      information is processed and valued. We created simulated meta-analyses based on
      idealized randomized studies (ie, perfect studies with no bias) to ensure
      differences in interpretations could only be due to reasoning. We recruited
      published meta-analysts using purposeful variables. We conducted 3 audio-recorded
      interviews per participant using structured and semi-structured interviews, with
      paraphrasing and reflective listening to enhance and verify responses.
      Recruitment and analysis of transcripts and field notes followed the principles
      of grounded theory (eg, theoretical saturation, constant comparative analysis).
      Results show the complexity of meta-analytic reasoning. At each step of the
      process, participants attempted to reconcile disparate forms of knowledge to
      determine a right answer (moral concern) and accurately draw a treatment effect
      (epistemological concern). The reasoning processes often shifted between
      considering the meta-analysis as if the data were whole, and as if the data were
      discrete components (individual studies). These findings highlight paradigmatic
      tensions regarding the epistemological premises of meta-analysis, resembling
      previous historical investigations of the functioning of scientific communities.
      In understanding why different meta-analysts interpret data differently, it may
      be unrealistic to expect objective homogenous recommendations based on meta
      analyses.

PMID- 28741809
TI  - Ferrocene-Based Hyperbranched Polytriazoles: Synthesis by Click Polymerization
      and Application as Precursors to Nanostructured Magnetoceramics.
AB  - Ferrocene-based polymers have drawn much attention in the past decades due to
      their unique properties and promising applications. However, the synthesis of
      hyperbranched polymers is still a great challenge. Here, two ferrocene-based
      hyperbranched polytriazoles with high molecular weights are facilely prepared by
      the click polymerization reactions of ferrocene-containing diazides (1) and
      tris(4-ethynylphenyl)amine (2) using Cu(PPh3 )3 Br as catalyst in
      dimethylformamide at 60  degrees C for 5 and 9 h in satisfactory yields of 54.0%
      and 52.3%. The resulting polytriazoles are soluble in common organic solvents and
      thermally stable, with 5% weight loss temperatures up to 307  degrees C. They can
      be used as precursors to produce nanostructured ceramics with good
      magnetizability by pyrolysis at elevated temperature.

PMID- 28741810
TI  - Gender Differences in Machine Learning Models of Trauma and Suicidal Ideation in
      Veterans of the Iraq and Afghanistan Wars.
AB  - Suicide rates among recent veterans have led to interest in risk identification.
      Evidence of gender-and trauma-specific predictors of suicidal ideation
      necessitates the use of advanced computational methods capable of elucidating
      these important and complex associations. In this study, we used machine learning
      to examine gender-specific associations between predeployment and military
      factors, traumatic deployment experiences, and psychopathology and suicidal
      ideation (SI) in a national sample of veterans deployed during the Iraq and
      Afghanistan conflicts (n = 2,244). Classification, regression tree analyses, and
      random forests were used to identify associations with SI and determine their
      classification accuracy. Findings converged on several associations for men that
      included depression, posttraumatic stress disorder (PTSD), and somatic
      complaints. Sexual harassment during deployment emerged as a key factor that
      interacted with PTSD and depression and demonstrated a stronger association with
      SI among women. Classification accuracy for SI presence or absence was good based
      on the receiver operating characteristic area under the curve, men = .91, women =
      .92. The risk for SI was classifiable with good accuracy, with associations that
      varied by gender. The use of machine learning analyses allowed for the discovery
      of rich, nuanced results that should be replicated in other samples and may
      eventually be a basis for the development of gender-specific actuarial tools to
      assess SI risk among veterans.

PMID- 28741811
TI  - Authorship: Musings about guests and ghosts.

PMID- 28741812
TI  - Impact of binge eating disorder on functional impairment and work productivity in
      an adult community sample in the United States.
AB  - AIM: This study compared functioning and productivity in individuals meeting
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
      diagnostic criteria for binge eating disorder (BED) to those without BED.
      METHODS: A sample of US adults from the National Health and Wellness Survey
      completed an Internet survey in October 2013. In addition to BED diagnostic
      criteria, the survey assessed functional impairment and productivity,
      respectively, using the Sheehan Disability Scale (SDS) and Work Productivity and
      Activity Impairment (WPAI) questionnaire. Differences between BED and non-BED
      respondents were assessed using multivariate models controlling for factors,
      including age, sex and comorbidities. RESULTS: Of 22 397 respondents, 344 were
      categorised as BED respondents and 20 437 as non-BED respondents. Compared with
      non-BED respondents, BED respondents exhibited significantly (all P<.001) greater
      functional impairment on the SDS, as measured by mean+/-SD total (14.04+/-9.46 vs
      3.41+/-6.36), work/school (3.86+/-3.62 vs 1.01+/-2.21), social life/leisure
      activities (5.29+/-3.49 vs 1.22+/-2.33) and family life/home responsibilities
      (4.89+/-3.44 vs 1.18+/-2.26) scores. Adjusted odds ratios (95% CIs) indicated
      that BED respondents were more impaired than non-BED respondents on the
      work/school (4.24 [3.33-5.40]), social life/leisure activities (6.37 [4.97-8.15])
      and family life/home responsibilities (5.76 [4.51-7.34]) domains of the SDS. On
      the WPAI, BED respondents reported significantly (all P<.001) higher percentages
      (mean+/-SD) of absenteeism (9.59%+/-19.97% vs 2.90%+/-12.95%), presenteeism
      (30.00%+/-31.64% vs 10.86%+/-20.07%), work productivity loss (33.19%+/-33.85% vs
      12.60%+/-23.22%) and activity impairment (43.52%+/-34.36% vs 19.94%+/-27.22%)
      than non-BED respondents. CONCLUSIONS: The findings suggest individuals with BED
      experience considerable impairment in functioning and work productivity compared
      with individuals without BED.

PMID- 28741813
TI  - Peripheral arterial disease amongst British ethnic minorities in a community
      based population: The Ethnic-Echocardiographic Heart of England Screening Study
      (E-ECHOES).

PMID- 28741814
TI  - Carbon isotope evidence for recent climate-related enhancement of CO 2
      assimilation and peat accumulation rates in Antarctica.
AB  - Signy Island, maritime Antarctic, lies within the region of the Southern
      Hemisphere that is currently experiencing the most rapid rates of environmental
      change. In this study, peat cores up to 2 m in depth from four moss banks on
      Signy Island were used to reconstruct changes in moss growth and climatic
      characteristics over the late Holocene. Measurements included radiocarbon dating
      (to determine peat accumulation rates) and stable carbon isotope composition of
      moss cellulose (to estimate photosynthetic limitation by CO 2 supply and model CO
      2 assimilation rate). For at least one intensively 14 C-dated Chorisodontium
      aciphyllum moss peat bank, the vertical accumulation rate of peat was 3.9 mm yr-1
      over the last 30 years. Before the industrial revolution, rates of peat
      accumulation in all cores were much lower, at around 0.6-1 mm yr-1 . Carbon-13
      discrimination (Delta), corrected for background and anthropogenic source inputs,
      was used to develop a predictive model for CO 2 assimilation. Between 1680 and
      1900, there had been a gradual increase in Delta, and hence assimilation rate.
      Since 1800, assimilation has also been stimulated by the changes in atmospheric
      CO 2 concentration, but a recent decline in Delta (over the past 50-100 years)
      can perhaps be attributed to documented changes in temperature and/or
      precipitation. The overall increase in CO 2 assimilation rate (13 C proxy) and
      enhanced C accumulation (14 C proxy) are consistent with warmer and wetter
      conditions currently generating higher growth rates than at any time in the past
      three millennia, with the decline in Delta perhaps compensated by a longer
      growing season.

PMID- 28741815
TI  - Shifts in soil organic carbon for plantation and pasture establishment in native
      forests and grasslands of South America.
AB  - The replacement of native vegetation by pastures or tree plantations is
      increasing worldwide. Contradictory effects of these land use transitions on the
      direction of changes in soil organic carbon (SOC) stocks, quality, and vertical
      distribution have been reported, which could be explained by the characteristics
      of the new or prior vegetation, time since vegetation replacement, and
      environmental conditions. We used a series of paired-field experiments and a
      literature synthesis to evaluate how these factors affect SOC contents in
      transitions between tree- and grass-dominated (grazed) ecosystems in South
      America. Both our field and literature approaches showed that SOC changes (0-20
      cm of depth) were independent of the initial native vegetation (forest,
      grassland, or savanna) but strongly dependent on the characteristics of the new
      vegetation (tree plantations or pastures), its age, and precipitation. Pasture
      establishment increased SOC contents across all our precipitation gradient and C
      gains were greater as pastures aged. In contrast, tree plantations increased SOC
      stocks in arid sites but decreased them in humid ones. However, SOC losses in
      humid sites were counterbalanced by the effect of plantation age, as plantations
      increased their SOC stocks as plantations aged. A multiple regression model
      including age and precipitation explained more than 50% (p < 0.01) of SOC changes
      observed after sowing pastures or planting trees. The only clear shift observed
      in the vertical distribution of SOC occurred when pastures replaced native
      forests, with SOC gains in the surface soil but losses at greater depths. The
      changes in SOC stocks occurred mainly in the silt+clay soil size fraction (MAOM),
      while SOC stocks in labile (POM) fraction remained relatively constant. Our
      results can be considered in designing strategies to increase SOC storage and
      soil fertility and highlight the importance of precipitation, soil depth, and age
      in determining SOC changes across a range of environments and land-use
      transitions.

PMID- 28741816
TI  - Combining projected changes in species richness and composition reveals climate
      change impacts on coastal Mediterranean fish assemblages.
AB  - Species Temporal Turnover (STT) is one of the most familiar metrics to assess
      changes in assemblage composition as a consequence of climate change. However,
      STT mixes two components in one metric, changes in assemblage composition caused
      by a process of species loss or gain (i.e. the nestedness component) and changes
      in assemblage composition caused by a process of species replacement (i.e. the
      species replacement component). Drawing on previous studies investigating spatial
      patterns of beta diversity, we propose measures of STT that allow analysing each
      component (species replacement vs. nestedness), separately. We also present a
      mapping strategy to simultaneously visualize changes in species richness and
      assemblage composition. To illustrate our approach, we used the Mediterranean
      coastal fish fauna as a case study. Using Bioclimatic Envelope Models (BEMs) we
      first projected the potential future climatic niches of 288 coastal Mediterranean
      fish species based on a global warming scenario. We then aggregated
      geographically the species-level projections to analyse the projected changes in
      species richness and composition. Our results show that projected changes in
      assemblage composition are caused by different processes (species replacement vs.
      nestedness) in several areas of the Mediterranean Sea. In addition, our mapping
      strategy highlights that the coastal fish fauna in several regions of the
      Mediterranean Sea could experience a 'cul-de-sac' effect if exposed to climate
      warming. Overall, the joint exploration of changes in species richness and
      composition coupled with the distinction between species replacement and
      nestedness bears important information for understanding the nature of climate
      change impacts on biodiversity. These methodological advances should help
      decision-makers in prioritizing action in the areas facing the greatest
      vulnerability to climate.

PMID- 28741817
TI  - Seasonal sea ice cover as principal driver of spatial and temporal variation in
      depth extension and annual production of kelp in Greenland.
AB  - We studied the depth distribution and production of kelp along the Greenland
      coast spanning Arctic to sub-Arctic conditions from 78 oN to 64 oN. This covers a
      wide range of sea ice conditions and water temperatures, with those presently
      realized in the south likely to move northwards in a warmer future. Kelp forests
      occurred along the entire latitudinal range, and their depth extension and
      production increased southwards presumably in response to longer annual ice-free
      periods and higher water temperature. The depth limit of 10% kelp cover was 9-14
      m at the northernmost sites (77-78 oN) with only 94-133 ice-free days per year,
      but extended to depths of 21-33 m further south (73 oN-64 oN) where >160 days per
      year were ice-free, and annual production of Saccharina longicruris and S.
      latissima, measured as the size of the annual blade, ranged up to sevenfold among
      sites. The duration of the open-water period, which integrates light and
      temperature conditions on an annual basis, was the best predictor (relative to
      summer water temperature) of kelp production along the latitude gradient,
      explaining up to 92% of the variation in depth extension and 80% of the variation
      in kelp production. In a decadal time series from a high Arctic site (74 oN),
      inter-annual variation in sea ice cover also explained a major part (up to 47%)
      of the variation in kelp production. Both spatial and temporal data sets thereby
      support the prediction that northern kelps will play a larger role in the coastal
      marine ecosystem in a warmer future as the length of the open-water period
      increases. As kelps increase carbon-flow and habitat diversity, an expansion of
      kelp forests may exert cascading effects on the coastal Arctic ecosystem.

PMID- 28741818
TI  - The role of harvest residue in rotation cycle carbon balance in loblolly pine
      plantations. Respiration partitioning approach.
AB  - Timber harvests remove a significant portion of ecosystem carbon. While some of
      the wood products moved off-site may last past the harvest cycle of the
      particular forest crop, the effect of the episodic disturbances on long-term on
      site carbon sequestration is unclear. The current study presents a 25 year carbon
      budget estimate for a typical commercial loblolly pine plantation in North
      Carolina, USA, spanning the entire rotation cycle. We use a chronosequence
      approach, based on 5 years of data from two adjacent loblolly pine plantations.
      We found that while the ecosystem is very productive (GEP up to 2900 g m-2  yr-1
      , NEE at maturity about 900 g C m-2  yr-1 ), the production of detritus does not
      offset the loss of soil C through heterotrophic respiration (RH ) on an annual
      basis. The input of dead roots at harvest may offset the losses, but there remain
      significant uncertainties about both the size and decomposition dynamics of this
      pool. The pulse of detritus produced at harvest resulted in a more than 60%
      increase in RH . Contrary to expectations, the peak of RH in relation to soil
      respiration (SR) did not occur immediately after the harvest disturbance, but in
      years 3 and 4, suggesting that a pool of roots may have remained alive for the
      first few years. On the other hand, the pulse of aboveground RH from coarse woody
      debris lasted only 2 years. The postharvest increase in RH was offset by a
      decrease in autotrophic respiration such that the total ecosystem respiration
      changed little. The observed flux rates show that even though the soil C pool may
      not necessarily decrease in the long-term, old soil C is definitely an active
      component in the site C cycle, contributing about 25-30% of the RH over the
      rotation cycle.

PMID- 28741819
TI  - Carbon outcomes of major land-cover transitions in SE Asia: great uncertainties
      and REDD+ policy implications.
AB  - Policy makers across the tropics propose that carbon finance could provide
      incentives for forest frontier communities to transition away from swidden
      agriculture (slash-and-burn or shifting cultivation) to other systems that
      potentially reduce emissions and/or increase carbon sequestration. However, there
      is little certainty regarding the carbon outcomes of many key land-use
      transitions at the center of current policy debates. Our meta-analysis of over
      250 studies reporting above- and below-ground carbon estimates for different land
      use types indicates great uncertainty in the net total ecosystem carbon changes
      that can be expected from many transitions, including the replacement of various
      types of swidden agriculture with oil palm, rubber, or some other types of
      agroforestry systems. These transitions are underway throughout Southeast Asia,
      and are at the heart of REDD+ debates. Exceptions of unambiguous carbon outcomes
      are the abandonment of any type of agriculture to allow forest regeneration (a
      certain positive carbon outcome) and expansion of agriculture into mature forest
      (a certain negative carbon outcome). With respect to swiddening, our meta
      analysis supports a reassessment of policies that encourage land-cover conversion
      away from these [especially long-fallow] systems to other more cash-crop-oriented
      systems producing ambiguous carbon stock changes - including oil palm and rubber.
      In some instances, lengthening fallow periods of an existing swidden system may
      produce substantial carbon benefits, as would conversion from intensely
      cultivated lands to high-biomass plantations and some other types of
      agroforestry. More field studies are needed to provide better data of above- and
      below-ground carbon stocks before informed recommendations or policy decisions
      can be made regarding which land-use regimes optimize or increase carbon
      sequestration. As some transitions may negatively impact other ecosystem
      services, food security, and local livelihoods, the entire carbon and noncarbon
      benefit stream should also be taken into account before prescribing transitions
      with ambiguous carbon benefits.

PMID- 28741820
TI  - Reproduction and seedling establishment of Picea glauca across the northernmost
      forest-tundra region in Canada.
AB  - The northern boundary of boreal forest and the ranges of tree species are
      expected to shift northward in response to climate warming, which will result in
      a decrease in the albedo of areas currently covered by tundra vegetation, an
      increase in terrestrial carbon sequestration, and an alteration of biodiversity
      in the current Low Arctic. Central to the prediction of forest expansion is an
      increase in the reproductive capacity and establishment of individual trees. We
      assessed cone production, seed viability, and transplanted seedling success of
      Picea glauca (Moench.) Voss. (white spruce) in the early 1990s and again in the
      late 2000s at four forest stand sites and eight tree island sites (clonal
      populations beyond present treeline) in the Mackenzie Delta region of the
      Northwest Territories, Canada. Over the past 20 years, average temperatures in
      this region have increased by 0.9  degrees C. This area has the northernmost
      forest-tundra ecotone in North America and is one of the few circumpolar regions
      where the northern limit of conifer trees reaches the Arctic Ocean. We found that
      cone production and seed viability did not change between the two periods of
      examination and that both variables decreased northward across the forest-tundra
      ecotone. Nevertheless, white spruce individuals at the northern limit of the
      forest-tundra ecotone produced viable seeds. Furthermore, transplanted seedlings
      were able to survive in the northernmost sites for 15 years, but there were no
      signs of natural regeneration. These results indicate that if climatic conditions
      continue to ameliorate, reproductive output will likely increase, but seedling
      establishment and forest expansion within the forest-tundra of this region is
      unlikely to occur without the availability of suitable recruitment sites.
      Processes that affect the availability of recruitment sites are likely to be
      important elsewhere in the circumpolar ecotone, and should be incorporated into
      models and predictions of climate change and its effects on the northern forest
      tundra ecotone.

PMID- 28741821
TI  - Dynamic macroecology and the future for biodiversity.
AB  - Reliable projections of climate-change impacts on biodiversity are vital in
      formulating conservation and management strategies that best retain biodiversity
      into the future. While recent modelling has focussed largely on individual
      species, macroecology has the potential to add significant value to these
      efforts, by incorporating important community-level constraints and processes.
      Here we show how a new dynamic macroecological approach can project climate
      change impacts collectively across all species in a diverse taxonomic group,
      overcoming shortfalls in our knowledge of biodiversity, while incorporating the
      key processes of dispersal and community assembly. Our approach applies a
      recently published technique (DynamicFOAM) to predict the present composition of
      every community, which form the initial conditions for a new metacommunity model
      (M-SET) that projects changes in composition over time, under specified climate
      and habitat scenarios. Applying this approach at fine resolution to plant
      biodiversity in Tasmania (2,051 species; 1,157,587 communities), we project high
      average turnover in community composition from 2010 to 2100 (mean Sorensen's
      dissimilarity = 0.71 (+/-7.0 * 10-5 )), with major reductions in species richness
      (32.9 (+/-0.02) species lost per community) and no plant species benefitting from
      climate change in the long term. We also demonstrate how our modelling approach
      can identify habitat likely to be of high value for retaining rare and poorly
      reserved species under climate change. Our analyses highlight the potential value
      of this dynamic macroecological approach, that incorporates key ecological
      processes in projecting climate change impacts for all species simultaneously and
      uses simple macroecological inputs that can be derived even for highly diverse
      and poorly studied taxa.

PMID- 28741822
TI  - Temperature adaptation of bacterial communities in experimentally warmed forest
      soils.
AB  - A detailed understanding of the influence of temperature on soil microbial
      activity is critical to predict future atmospheric CO2 concentrations and
      feedbacks to anthropogenic warming. We investigated soils exposed to 3-4 years of
      continuous 5  degrees C-warming in a field experiment in a temperate forest. We
      found that an index for the temperature adaptation of the microbial community,
      Tmin for bacterial growth, increased by 0.19  degrees C per 1  degrees C rise in
      temperature, showing a community shift towards one adapted to higher temperature
      with a higher temperature sensitivity (Q10(5-15  degrees C) increased by 0.08
      units per 1  degrees C). Using continuously measured temperature data from the
      field experiment we modelled in situ bacterial growth. Assuming that warming did
      not affect resource availability, bacterial growth was modelled to become 60%
      higher in warmed compared to the control plots, with the effect of temperature
      adaptation of the community only having a small effect on overall bacterial
      growth (<5%). However, 3 years of warming decreased bacterial growth, most likely
      due to substrate depletion because of the initially higher growth in warmed
      plots. When this was factored in, the result was similar rates of modelled in
      situ bacterial growth in warmed and control plots after 3 years, despite the
      temperature difference. We conclude that although temperature adaptation for
      bacterial growth to higher temperatures was detectable, its influence on annual
      bacterial growth was minor, and overshadowed by the direct temperature effect on
      growth rates.

PMID- 28741823
TI  - Recovery of ponderosa pine ecosystem carbon and water fluxes from thinning and
      stand-replacing fire.
AB  - Carbon uptake by forests is a major sink in the global carbon cycle, helping
      buffer the rising concentration of CO2 in the atmosphere, yet the potential for
      future carbon uptake by forests is uncertain. Climate warming and drought can
      reduce forest carbon uptake by reducing photosynthesis, increasing respiration,
      and by increasing the frequency and intensity of wildfires, leading to large
      releases of stored carbon. Five years of eddy covariance measurements in a
      ponderosa pine (Pinus ponderosa)-dominated ecosystem in northern Arizona showed
      that an intense wildfire that converted forest into sparse grassland shifted site
      carbon balance from sink to source for at least 15 years after burning. In
      contrast, recovery of carbon sink strength after thinning, a management practice
      used to reduce the likelihood of intense wildfires, was rapid. Comparisons
      between an undisturbed-control site and an experimentally thinned site showed
      that thinning reduced carbon sink strength only for the first two posttreatment
      years. In the third and fourth posttreatment years, annual carbon sink strength
      of the thinned site was higher than the undisturbed site because thinning reduced
      aridity and drought limitation to carbon uptake. As a result, annual maximum
      gross primary production occurred when temperature was 3  degrees C higher at the
      thinned site compared with the undisturbed site. The severe fire consistently
      reduced annual evapotranspiration (range of 12-30%), whereas effects of thinning
      were smaller and transient, and could not be detected in the fourth year after
      thinning. Our results show large and persistent effects of intense fire and minor
      and short-lived effects of thinning on southwestern ponderosa pine ecosystem
      carbon and water exchanges.

PMID- 28741824
TI  - Climate change, fuel and fire behaviour in a eucalypt forest.
AB  - A suite of models was used to examine the links between climate, fuels and fire
      behaviour in dry eucalypt forests in south-eastern Australia. Predictions from a
      downscaled climate model were used to drive models of fuel amount, the moisture
      content of fuels and two models of forest fire behaviour at a location in western
      Sydney in New South Wales, Australia. We found that a warming and drying climate
      produced lower fine fuel amounts, but greater availability of this fuel to burn
      due to lower moisture contents. Changing fuel load had only a small effect on
      fuel moisture. A warmer, drier climate increased rate of spread, an important
      measure of fire behaviour. Reduced fuel loads ameliorated climate-induced changes
      in fire behaviour for one model. Sensitivity analysis of the other fire model
      showed that changes in fuel amount induced changes in fire behaviour of a similar
      magnitude to that caused directly by sensitivity to climate. Projection of
      changes in fire risk requires modelling of changes in vegetation as well as
      changes in climate. Better understanding of climate change effects on vegetation
      structure is required.

PMID- 28741825
TI  - High arctic heath soil respiration and biogeochemical dynamics during summer and
      autumn freeze-in - effects of long-term enhanced water and nutrient supply.
AB  - In High Arctic NE Greenland, temperature and precipitation are predicted to
      increase during this century, however, relatively little information is available
      on the role of increased water supply on soil CO 2 efflux in dry, high arctic
      ecosystems. We measured soil respiration (Rsoil ) in summer and autumn of 2009 in
      combination with microbial biomass and nutrient availability during autumn freeze
      in at a dry, open heath in Zackenberg, NE Greenland. This tundra site has been
      subject to fully factorial manipulation consisting of increased soil water supply
      for 14 years, and occasional nitrogen (N) addition in pulses. Summer watering
      enhanced Rsoil during summer, but decreased Rsoil in the following autumn. We
      speculate that this is due to intensified depletion of recently fixed plant
      carbon by soil organisms. Hence, autumn soil microbial activity seems tightly
      linked to growing season plant production through plant-associated carbon pools.
      Nitrogen addition alone consistently increased Rsoil , but when water and
      nitrogen were added in combination, autumn Rsoil declined similarly to when water
      was added alone. Despite several freeze-thaw events, the microbial biomass carbon
      (C) remained constant until finally being reduced by ~60% in late September. In
      spite of significantly reduced microbial biomass C and phosphorus (P), microbial
      N did not change. This suggests N released from dead microbes was quickly
      assimilated by surviving microbes. We observed no change in soil organic matter
      content after 14 years of environmental manipulations, suggesting high ecosystem
      resistance to environmental changes.

PMID- 28741826
TI  - Sea anemones may thrive in a high CO2 world.
AB  - Increased seawater pCO2 , and in turn 'ocean acidification' (OA), is predicted to
      profoundly impact marine ecosystem diversity and function this century. Much
      research has already focussed on calcifying reef-forming corals (Class: Anthozoa)
      that appear particularly susceptible to OA via reduced net calcification.
      However, here we show that OA-like conditions can simultaneously enhance the
      ecological success of non-calcifying anthozoans, which not only play key
      ecological and biogeochemical roles in present day benthic ecosystems but also
      represent a model organism should calcifying anthozoans exist as less calcified
      (soft-bodied) forms in future oceans. Increased growth (abundance and size) of
      the sea anemone (Anemonia viridis) population was observed along a natural CO2
      gradient at Vulcano, Italy. Both gross photosynthesis (PG ) and respiration (R)
      increased with pCO2 indicating that the increased growth was, at least in part,
      fuelled by bottom up (CO2 stimulation) of metabolism. The increase of PG
      outweighed that of R and the genetic identity of the symbiotic microalgae
      (Symbiodinium spp.) remained unchanged (type A19) suggesting proximity to the
      vent site relieved CO2 limitation of the anemones' symbiotic microalgal
      population. Our observations of enhanced productivity with pCO2 , which are
      consistent with previous reports for some calcifying corals, convey an increase
      in fitness that may enable non-calcifying anthozoans to thrive in future
      environments, i.e. higher seawater pCO2 . Understanding how CO2 -enhanced
      productivity of non- (and less-) calcifying anthozoans applies more widely to
      tropical ecosystems is a priority where such organisms can dominate benthic
      ecosystems, in particular following localized anthropogenic stress.

PMID- 28741827
TI  - Different inter-annual responses to availability and form of nitrogen explain
      species coexistence in an alpine meadow community after release from grazing.
AB  - Plant species and functional groups in nitrogen (N) limited communities may
      coexist through strong eco-physiological niche differentiation, leading to
      idiosyncratic responses to multiple nutrition and disturbance regimes. Very
      little is known about how such responses depend on the availability of N in
      different chemical forms. Here we hypothesize that idiosyncratic year-to-year
      responses of plant functional groups to availability and form of nitrogen explain
      species coexistence in an alpine meadow community after release from grazing. We
      conducted a 6 year N addition experiment in an alpine meadow on the Tibetan
      Plateau released from grazing by livestock. The experimental design featured
      three N forms (ammonium, nitrate, and ammonium nitrate), crossed with three
      levels of N supply rates (0.375, 1.500 and 7.500 g N m-2  yr-1 ), with
      unfertilized treatments without and with light grazing as controls. All
      treatments showed increasing productivity and decreasing species richness after
      cessation of grazing and these responses were stronger at higher N rates.
      Although N forms did not affect aboveground biomass at community level, different
      functional groups did show different responses to N chemical form and supply rate
      and these responses varied from year to year. In support of our hypothesis, these
      idiosyncratic responses seemed to enable a substantial diversity and biomass of
      sedges, forbs, and legumes to still coexist with the increasingly productive
      grasses in the absence of grazing, at least at low and intermediate N
      availability regimes. This study provides direct field-based evidence in support
      of the hypothesis that idiosyncratic and annually varying responses to both N
      quantity and quality may be a key driver of community structure and species
      coexistence. This finding has important implications for the diversity and
      functioning of other ecosystems with spatial and temporal variation in available
      N quantity and quality as related to changing atmospheric N deposition, land-use,
      and climate-induced soil warming.

PMID- 28741828
TI  - The costs of keeping cool in a warming world: implications of high temperatures
      for foraging, thermoregulation and body condition of an arid-zone bird.
AB  - Recent mass mortalities of bats, birds and even humans highlight the substantial
      threats that rising global temperatures pose for endotherms. Although less
      dramatic, sublethal fitness costs of high temperatures may be considerable and
      result in changing population demographics. Endothermic animals exposed to high
      environmental temperatures can adjust their behaviour (e.g. reducing activity) or
      physiology (e.g. elevating rates of evaporative water loss) to maintain body
      temperatures within tolerable limits. The fitness consequences of these
      adjustments, in terms of the ability to balance water and energy budgets and
      therefore maintain body condition, are poorly known. We investigated the effects
      of daily maximum temperature on foraging and thermoregulatory behaviour as well
      as maintenance of body condition in a wild, habituated population of Southern
      Pied Babblers Turdoides bicolor. These birds inhabit a hot, arid area of southern
      Africa where they commonly experience environmental temperatures exceeding
      optimal body temperatures. Repeated measurements of individual behaviour and body
      mass were taken across days varying in maximum air temperature. Contrary to
      expectations, foraging effort was unaffected by daily maximum temperature.
      Foraging efficiency, however, was lower on hotter days and this was reflected in
      a drop in body mass on hotter days. When maximum air temperatures exceeded 35.5 
      degrees C, individuals no longer gained sufficient weight to counter typical
      overnight weight loss. This reduction in foraging efficiency is likely driven, in
      part, by a trade-off with the need to engage in heat-dissipation behaviours. When
      we controlled for temperature, individuals that actively dissipated heat while
      continuing to forage experienced a dramatic decrease in their foraging
      efficiency. This study demonstrates the value of investigations of temperature
      dependent behaviour in the context of impacts on body condition, and suggests
      that increasingly high temperatures will have negative implications for the
      fitness of these arid-zone birds.

PMID- 28741829
TI  - Tracking climate impacts on the migratory monarch butterfly.
AB  - Understanding the impacts of climate on migratory species is complicated by the
      fact that these species travel through several climates that may be changing in
      diverse ways throughout their complete migratory cycle. Most studies are not
      designed to tease out the direct and indirect effects of climate at various
      stages along the migration route. We assess the impacts of spring and summer
      climate conditions on breeding monarch butterflies, a species that completes its
      annual migration cycle over several generations. No single, broad-scale climate
      metric can explain summer breeding phenology or the substantial year-to-year
      fluctuations observed in population abundances. As such, we built a Poisson
      regression model to help explain annual arrival times and abundances in the
      Midwestern United States. We incorporated the climate conditions experienced both
      during a spring migration/breeding phase in Texas as well as during subsequent
      arrival and breeding during the main recruitment period in Ohio. Using data from
      a state-wide butterfly monitoring network in Ohio, our results suggest that
      climate acts in conflicting ways during the spring and summer seasons. High
      spring precipitation in Texas is associated with the largest annual population
      growth in Ohio and the earliest arrival to the summer breeding ground, as are
      intermediate spring temperatures in Texas. On the other hand, the timing of
      monarch arrivals to the summer breeding grounds is not affected by climate
      conditions within Ohio. Once in Ohio for summer breeding, precipitation has
      minimal impacts on overall abundances, whereas warmer summer temperatures are
      generally associated with the highest expected abundances, yet this effect is
      mitigated by the average seasonal temperature of each location in that the
      warmest sites receive no benefit of above average summer temperatures. Our
      results highlight the complex relationship between climate and performance for a
      migrating species and suggest that attempts to understand how monarchs will be
      affected by future climate conditions will be challenging.

PMID- 28741830
TI  - Do nitrogen fertilizers stimulate or inhibit methane emissions from rice fields?
AB  - In rice cultivation, there are controversial reports on net impacts of nitrogen
      (N) fertilizers on methane (CH 4 ) emissions. Nitrogen fertilizers increase crop
      growth as well as alter CH 4 producing (Methanogens) and consuming
      (Methanotrophs) microbes, and thereby produce complex effects on CH 4 emissions.
      Objectives of this study were to determine net impact of N fertilizers on CH 4
      emissions and to identify their underlying mechanisms in the rice soils. Database
      was obtained from 33 published papers that contained CH 4 emissions observations
      from N fertilizer (28-406 kg N ha-1 ) treatment and its control. Results have
      indicated that N fertilizers increased CH 4 emissions in 98 of 155 data pairs in
      rice soils. Response of CH 4 emissions per kg N fertilizer was significantly (P <
      0.05) greater at < 140 kg N ha-1 than > 140 kg N ha-1 indicating that substrate
      switch from CH 4 to ammonia by Methanotrophs may not be a dominant mechanism for
      increased CH 4 emissions. On the contrary, decreased CH 4 emission in
      intermittent drainage by N fertilizers has suggested the stimulation of
      Methanotrophs in rice soils. Effects of N fertilizer stimulated Methanotrophs in
      reducing CH 4 emissions were modified by the continuous flood irrigation due to
      limitation of oxygen to Methanotrophs. Greater response of CH 4 emissions per kg
      N fertilizer in urea than ammonia sulfate probably indicated the interference of
      sulfate in the CH 4 production process. Overall, response of CH 4 emissions to N
      fertilizers was correlated with N-induced crop yield (r = +0.39; P < 0.01),
      probably due to increased carbon substrates for Methanogens. Using CH 4 emission
      observations, this meta-analysis has identified dominant microbial processes that
      control net effects of N fertilizers on CH 4 emissions in rice soils. Finally, we
      have provided a conceptual model that included microbial processes and
      controlling factors to predict effects of N fertilizers on CH 4 emissions in rice
      soils.

PMID- 28741831
TI  - Are responses of herbivores to environmental variability spatially consistent in
      alpine ecosystems?
AB  - Animal responses to global climate variation might be spatially inconsistent.
      This may arise from spatial variation in factors limiting populations' growth or
      from differences in the links between global climate patterns and ecologically
      relevant local climate variation. For example, the North Atlantic Oscillation
      (NAO) has a spatially consistent relation to temperature, but inconsistent
      spatial relation to snow depth in Scandinavia. Furthermore, there are multiple
      mechanistic ways by which climate may limit animal populations, involving both
      direct effects through thermoregulation and indirect pathways through trophic
      interactions. It is conceptually appealing to directly model the predicted
      mechanistic links. This includes the use of climate variables mimicking such
      interactions, for example, to use growing degree days (GDD) as a proxy for plant
      growth rather than average monthly temperature. Using a unique database of autumn
      body mass of 83331 domestic lambs from the period 1992-2007 in four alpine ranges
      in Norway, we demonstrate the utility of hierarchical, mechanistic path models
      fitted using a Bayesian approach to analyse explicitly predicted relationships
      among environmental variables and between lamb body mass and the environmental
      variables. We found large spatial variation in strength of responses of autumn
      lamb body mass to the NAO, to a proxy for plant growth in spring (the Normalized
      Difference Vegetation Index, NDVI) and effects even differed in direction to
      local summer climate. Average local temperature outperformed GDD as a predictor
      of the NDVI, whereas the NAO index in two areas outperformed local weather
      variables as a predictor of lamb body mass, despite the weaker mechanistic link.
      Our study highlights that spatial variation in strength of herbivore responses
      may arise from several processes. Furthermore, mechanistically more appealing
      measures do not always increase predictive power due to scale of measurement and
      since global measures may provide more relevant "weather packages" for larger
      scales.

PMID- 28741832
TI  - Strategic planning for instream flow restoration: a case study of potential
      climate change impacts in the central Columbia River basin.
AB  - We provide a case study prioritizing instream flow restoration activities by sub
      basin according to the habitat needs of Endangered Species Act (ESA)-listed
      salmonids relative to climate change in the central Columbia River basin in
      Washington State (USA). The objective is to employ scenario analysis to inform
      and improve existing instream flow restoration projects. We assess the
      sensitivity of late summer (July, August, and September) flows to the following
      scenario simulations - singly or in combination: climate change, changes in the
      quantity of water used for irrigation and possible changes to existing water
      resource policy. Flows for four sub-basins were modeled using the Water
      Evaluation and Planning system (WEAP) under historical and projected conditions
      of 2020 and 2040 for each scenario. Results indicate that Yakima will be the most
      flow-limited sub-basin with average reductions in streamflow of 41% under climate
      conditions of 2020 and 56% under 2040 conditions; 1.3-2.5 times greater than
      those of other sub-basins. In addition, irrigation plays a key role in the
      hydrology of the Yakima sub-basin - with flow reductions ranging from 78% to 90%
      under severe to extreme (i.e., 20-40%) increases in agricultural water use (2.0
      4.4 times the reductions in the other sub-basins). The Yakima and Okanogan sub
      basins are the most responsive to simulations of flow-bolstering policy change
      (providing salmon with first priority water allocation and at biologically
      relevant flows), as demonstrated by 91-100% target flows attained. The Wenatchee
      and Methow sub-basins do not exhibit similar responsiveness to simulated policy
      changes. Considering climate change only, we conclude that flow restoration
      should be prioritized first in the Yakima and Wenatchee sub-basins, and second in
      the Okanogan and Methow. Considering both climate change and possible policy
      changes, we recommend that the Yakima sub-basin receive the highest priority for
      flow restoration activities to sustain critical instream habitat for ESA-listed
      salmonids.

PMID- 28741833
TI  - Marine invertebrate skeleton size varies with latitude, temperature and carbonate
      saturation: implications for global change and ocean acidification.
AB  - There is great concern over the future effects of ocean acidification on marine
      organisms, especially for skeletal calcification, yet little is known of natural
      variation in skeleton size and composition across the globe, and this is a
      prerequisite for identifying factors currently controlling skeleton mass and
      thickness. Here, taxonomically controlled latitudinal variations in shell
      morphology and composition were investigated in bivalve and gastropod molluscs,
      brachiopods, and echinoids. Total inorganic content, a proxy for skeletal CaCO3 ,
      decreased with latitude, decreasing seawater temperature, and decreasing seawater
      carbonate saturation state (for CaCO3 as calcite (Omegacal )) in all taxa. Shell
      mass decreased with latitude in molluscs and shell inorganic content decreased
      with latitude in buccinid gastropods. Shell thickness decreased with latitude in
      buccinid gastropods (excepting the Australian temperate buccinid) and echinoids,
      but not brachiopods and laternulid clams. In the latter, the polar species had
      the thickest shell. There was no latitudinal trend in shell thickness within
      brachiopods. The variation in trends in shell thickness by taxon suggests that in
      some circumstances ecological factors may override latitudinal trends.
      Latitudinal gradients may produce effects similar to those of future CO2 -driven
      ocean acidification on CaCO3 saturation state. Responses to latitudinal trends in
      temperature and saturation state may therefore be useful in informing predictions
      of organism responses to ocean acidification over long-term adaptive timescales.

PMID- 28741834
TI  - Long-term variability and rainfall control of savanna fire regimes in equatorial
      East Africa.
AB  - Fires burning the vast grasslands and savannas of Africa significantly influence
      the global carbon cycle. Projecting the impacts of future climate change on fire
      mediated biogeochemical processes in these dry tropical ecosystems requires
      understanding of how various climate factors influence regional fire regimes. To
      examine climate-vegetation-fire linkages in dry savanna, we conducted macroscopic
      and microscopic charcoal analysis on the sediments of the past 25 000 years from
      Lake Challa, a deep crater lake in equatorial East Africa. The charcoal-inferred
      shifts in local and regional fire regimes were compared with previously published
      reconstructions of temperature, rainfall, seasonal drought severity, and
      vegetation dynamics to evaluate millennial-scale drivers of fire occurrence. Our
      charcoal data indicate that fire in the dry lowland savanna of southeastern Kenya
      was not fuel-limited during the Last Glacial Maximum (LGM) and Late Glacial, in
      contrast to many other regions throughout the world. Fire activity remained high
      at Lake Challa probably because the relatively high mean-annual temperature (~22 
      degrees C) allowed productive C4 grasses with high water-use efficiency to
      dominate the landscape. From the LGM through the middle Holocene, the relative
      importance of savanna burning in the region varied primarily in response to
      changes in rainfall and dry-season length, which were controlled by orbital
      insolation forcing of tropical monsoon dynamics. The fuel limitation that
      characterizes the region's fire regime today appears to have begun around 5000
      6000 years ago, when warmer interglacial conditions coincided with prolonged
      seasonal drought. Thus, insolation-driven variation in the amount and seasonality
      of rainfall during the past 25 000 years altered the immediate controls on fire
      occurrence in the grass-dominated savannas of eastern equatorial Africa. These
      results show that climatic impacts on dry-savanna burning are heterogeneous
      through time, with important implications for efforts to anticipate future shifts
      in fire-mediated ecosystem processes.

PMID- 28741835
TI  - No stimulation of nitrogen fixation by non-filamentous diazotrophs under elevated
      CO2 in the South Pacific.
AB  - Nitrogen fixation by diazotrophic cyanobacteria is a critical source of new
      nitrogen to the oligotrophic surface ocean. Research to date indicates that some
      diazotroph groups may increase nitrogen fixation under elevated pCO2 . To test
      this in natural plankton communities, four manipulation experiments were carried
      out during two voyages in the South Pacific (30-35o S). High CO2 treatments,
      produced using 750 ppmv CO2 to adjust pH to 0.2 below ambient, and 'Greenhouse'
      treatments (0.2 below ambient pH and ambient temperature +3  degrees C), were
      compared with Controls in trace metal clean deckboard incubations in triplicate.
      No significant change was observed in nitrogen fixation in either the High CO2 or
      Greenhouse treatments over 5 day incubations. qPCR measurements and optical
      microscopy determined that the diazotroph community was dominated by Group A
      unicellular cyanobacteria (UCYN-A), which may account for the difference in
      response of nitrogen fixation under elevated CO2 to that reported previously for
      Trichodesmium. This may reflect physiological differences, in that the greater
      cell surface area:volume of UCYN-A and its lack of metabolic pathways involved in
      carbon fixation may confer no benefit under elevated CO2 . However, multiple
      environmental controls may also be a factor, with the low dissolved iron
      concentrations in oligotrophic surface waters limiting the response to elevated
      CO2 . If nitrogen fixation by UCYN-A is not stimulated by elevated pCO2 , then
      future increases in CO2 and warming may alter the regional distribution and
      dominance of different diazotroph groups, with implications for dissolved iron
      availability and new nitrogen supply in oligotrophic regions.

PMID- 28741836
TI  - A Land System representation for global assessments and land-use modeling.
AB  - Current global scale land-change models used for integrated assessments and
      climate modeling are based on classifications of land cover. However, land-use
      management intensity and livestock keeping are also important aspects of land
      use, and are an integrated part of land systems. This article aims to classify,
      map, and to characterize Land Systems (LS) at a global scale and analyze the
      spatial determinants of these systems. Besides proposing such a classification,
      the article tests if global assessments can be based on globally uniform
      allocation rules. Land cover, livestock, and agricultural intensity data are used
      to map LS using a hierarchical classification method. Logistic regressions are
      used to analyze variation in spatial determinants of LS. The analysis of the
      spatial determinants of LS indicates strong associations between LS and a range
      of socioeconomic and biophysical indicators of human-environment interactions.
      The set of identified spatial determinants of a LS differs among regions and
      scales, especially for (mosaic) cropland systems, grassland systems with
      livestock, and settlements. (Semi-)Natural LS have more similar spatial
      determinants across regions and scales. Using LS in global models is expected to
      result in a more accurate representation of land use capturing important aspects
      of land systems and land architecture: the variation in land cover and the link
      between land-use intensity and landscape composition. Because the set of most
      important spatial determinants of LS varies among regions and scales, land-change
      models that include the human drivers of land change are best parameterized at
      sub-global level, where similar biophysical, socioeconomic and cultural
      conditions prevail in the specific regions.

PMID- 28741838
TI  - Intrauterine exposure to oestradiol promotes sex-specific differential effects on
      the prostatic development of neonate gerbils.
AB  - The effects of intrauterine exposure to 17beta-oestradiol (E2) are well studied
      for the male prostate and there are accumulating evidences that the exposure to
      high dosages leads to a hypomorphic development. However, there is a lack of
      information about the effects of intrauterine exposure to E2 in the prostate of
      rodent females, and such research becomes relevant in view of the presence of
      functional prostate in a proportion of women, and the morphophysiological
      similarities between the prostate of female rodents and the prostate of women.
      This study uses histochemical, immunohistochemical, immunofluorescence and three
      dimensional (3D) reconstruction techniques to evaluate the effects of
      intrauterine exposure to E2 (500 BW/d) on neonatal prostate development in both
      male and female gerbils. It was verified that intrauterine exposure to E2
      promotes epithelial proliferation and growth of prostatic budding in females,
      whereas in males the prostatic budding shows hypomorphic growth in the VMP
      (Ventral Mesenchymal Pad) as well as reduced epithelial proliferation. Together,
      the data demonstrate that intrauterine exposure to E2 causes different effects on
      male and female prostates of the gerbil even at the early postnatal development
      of the gland.

PMID- 28741839
TI  - Feasibility of spacers to facilitate postoperative radiotherapy for
      retroperitoneal sarcomas.
AB  - INTRODUCTION: The role and timing of postoperative radiotherapy (PORT) in the
      management of retroperitoneal sarcoma (RPS) remains controversial. METHOD: This
      is a retrospective cohort review of patients undergoing curative resection for
      RPS at a single institution between January 2011 and July 2016. Patient selection
      was through the South Australian Soft Tissue Tumour Multidisciplinary Group (MDT)
      based at Royal Adelaide Hospital. An individualised approach, including
      assessment of resectability, histopathological grade and subtype, and
      radiotherapy considerations, was taken for each patient. Patients offered
      preoperative radiotherapy or palliation were excluded. A saline-filled spacer was
      inserted following operative resection. Radiotherapy commenced postoperatively.
      Patients underwent laparotomy to remove the device approximately 6 weeks post
      completion of PORT. Primary endpoints were technical feasibility, perioperative
      morbidity and radiation toxicity. Secondary endpoints were local recurrence (LR),
      distant recurrence (DR) and death. RESULTS: During the study period, 40 patients
      with RPS were managed through the MDT. Twelve patients (ages 33-78) underwent
      PORT utilising spacers. Radiotherapy toxicity was reported in four patients and
      extensive adhesions observed in another four patients during spacer removal.
      Median follow-up was 35 months (range 4-60). Seven patients remain alive and
      disease free. Four patients developed LR, three developed DR. Three patients
      died; two with DR and one with LR. Two patients with recurrent/progressive
      disease are alive; one with DR and one with LR. CONCLUSION: Use of intraoperative
      spacers to facilitate PORT is feasible, with acceptable toxicity following
      resection of RPS. Patient selection for this approach remains to be determined.

PMID- 28741840
TI  - Stepwise Growth of Fullerene Nanoparticles through Guest Exchange of gamma
      Cyclodextrin Complexes in Water.
AB  - Stepwise growth of fullerene nanoparticles (nCx ; x=60 or 70) was performed
      through guest exchange of a gamma-cyclodextrin (gamma-CD) complex. Fullerenes
      bicapped by gamma-CD were mixed with presynthesized nCx in the presence of
      poly(ethylene glycol) (PEG) in water. Fullerenes expelled from the gamma-CD hosts
      by PEG were piled on the original nCx , resulting in growth of nCx . This process
      could be repeated and the size of nCx increased according to the number of growth
      steps. The growth of fullerene nanoparticles was confirmed by UV/Vis absorption
      spectroscopy, dynamic light scattering measurements, and TEM observations. The
      stepwise growth method also enabled the preparation of C60 /C70 core/shell
      fullerene nanoparticles, which had the ability to photogenerate active oxygen, 1
      O2 .

PMID- 28741837
TI  - Immunological and virological response to antiretroviral treatment in migrant and
      native men and women in Western Europe; is benefit equal for all?
AB  - OBJECTIVES: The aim of the study was to evaluate differences in immunovirological
      response to combination antiretroviral therapy (cART) in migrant and native men
      and women within a European collaboration of HIV cohorts Collaboration of
      Observational HIV Epidemiological Research in Europ (COHERE) in EuroCoord, 2004
      2013. METHODS: Migrants were defined as those with geographical origin (GO)
      different from the reporting country and were grouped as originating from Western
      Europe and Western Countries (WEWC), Eastern Europe (EE), North Africa and the
      Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), Caribbean (CRB)
      and Asia/Oceania (ASIA/OCE). Native (NAT) individuals were defined as those
      originating from the reporting country. CD4 cell counts were modelled using
      piecewise linear mixed-effects models with two slopes, whereas models to estimate
      subdistribution hazard ratios (sHRs) were used for time to virological response
      (VR) (i.e. time from cART initiation to the first of two successive HIV RNA
      measurements < 400 HIV-1 RNA copies/ml). RESULTS: Of 32 817 individuals, 25 799
      (78.6%) were men. The percentage of migrants was higher in women (48.9%) than in
      men (21.2%) and migrants from SSA accounted for the largest migrant group (29.9%
      in men and 63.3% in women). Migrant men and women from SSA started at lower CD4
      cell counts than NAT individuals, which remained lower over time. VR was >= 85%
      at 12 months for all groups except CRB women (77.7%). Compared with NAT men and
      women, lower VR was experienced by NAME [sHR 0.91; 95% confidence interval (CI)
      0.86-0.97] and SSA (sHR 0.88; 95% CI 0.82-0.95) men and CRB (sHR 0.77; 85% CI
      0.67-0.89) women, respectively. CONCLUSIONS: Immunovirological response to cART
      in Western Europe varies by GO and sex of patients. ART benefits are not equal
      for all, underlining the point that efforts need to prioritize those most in
      need.

PMID- 28741841
TI  - Pulmonary Valve Opening With Two Rotary Left Ventricular Assist Devices for
      Biventricular Support.
AB  - Right ventricular failure is a common complication associated with rotary left
      ventricular assist device (LVAD) support. Currently, there is no clinically
      approved long-term rotary right ventricular assist device (RVAD). Instead,
      clinicians have implanted a second rotary LVAD as RVAD in biventricular support.
      To prevent pulmonary hypertension, the RVAD must be operated by either reducing
      pump speed or banding the outflow graft. These modes differ in hydraulic
      performance, which may affect the pulmonary valve opening (PVO) and subsequently
      cause fusion, valvular insufficiency, and thrombus formation. This study aimed to
      compare PVO with the RVAD operated at reduced speed or with a banded outflow
      graft. Baseline conditions of systemic normal, hypo, and hypertension with severe
      biventricular failure were simulated in a mock circulation loop. Biventricular
      support was provided with two rotary VentrAssist LVADs with cardiac output
      restored to 5 L/min in banded outflow and reduced speed conditions, and systemic
      and pulmonary vascular resistances (PVR) were manipulated to determine the range
      of conditions that allowed PVO without causing left ventricular suction. Finally,
      RVAD sine wave speed modulation (+/-550 rpm) strategies (co- and counter
      pulsation) were implemented to observe the effect on PVO. For each condition,
      outflow banding had higher PVR (97 +/- 20 dyne/s/cm5 higher) for when the
      pulmonary valve closed compared to reduced speed. In addition, counter-pulsation
      demonstrated greater PVO than co-pulsation and constant speed. For the purpose of
      reducing the risks of pulmonary valve insufficiency, fusion, and thrombotic
      event, this study recommends a RVAD with a steeper H-Q gradient by banding and
      further exploration of RVAD speed modulation.

PMID- 28741842
TI  - Synergistic Cu/Pd Catalysis for Enantioselective Allylic Alkylation of Aldimine
      Esters: Access to alpha,alpha-Disubstituted alpha-Amino Acids.
AB  - An unprecedented enantioselective allylic alkylation of readily available
      aldimine esters has been developed, and is catalyzed by a synergistic Cu/Pd
      catalyst system. This strategy provides facile access to nonproteinogenic
      alpha,alpha-disubstituted alpha-amino acids in high yield with excellent
      enantioselectivity. The more challenging double allylic alkylation of glycinate
      derived imine esters was also realized. Furthermore, this methodology was applied
      for the construction of the key intermediate of PLG peptidomimetics.

PMID- 28741843
TI  - Niche differences may explain the geographic distribution of cytotypes in
      Erysimum mediohispanicum.
AB  - Polyploidisation has played an important role in plant diversification, and
      variation in ploidy level may be found not only between species of the same
      genus, but also within a single species. Although establishing the adaptive
      significance of polyploidy to explain the geographic distribution of cytotypes is
      challenging, the occurrence of different cytotypes in different ecological niches
      may suggest an adaptive role of genome duplication. We studied the adaptive
      significance of the geographic distribution of cytotypes across the entire
      distribution range of the endemic Erysimum mediohispanicum (Brassicaceae). For
      that, we have used climate variables, population elevation and soil properties to
      model ecological niches for the different cytotypes. In addition, we analysed the
      effect that ploidy level has on the floral phenotype. We found a clear geographic
      pattern in the distribution of cytotypes, with diploid individuals occurring in
      the southernmost part of the distribution range, while tetraploids were found in
      the northern area. A contact (mosaic) zone between both cytotypes was identified,
      but diploids and tetraploids occur in sympatry in only one population (although
      in a highly unbalanced proportion). Gene flow between different cytotypes seems
      to be negligible, as evident from an almost complete absence of triploids and
      other minority cytotypes. Niches occupied by both cytotypes showed subtle, but
      significant differences, even in the contact zone. Precipitation was higher in
      regions occupied by tetraploid individuals, which present wider corolla tubes and
      thinner but taller stalks than diploids. Our findings highlight the potential
      role of polyploidy in the ecological adaptation of E. mediohispanicum to both
      abiotic factors and biotic interactions.

PMID- 28741844
TI  - Regulated Drug Release Abilities of Calcium Carbonate-Gelatin Hybrid Nanocarriers
      Fabricated via a Self-Organizational Process.
AB  - In this study, we investigated the drug-releasing behavior of a calcium carbonate
      (CaCO3 )-gelatin hybrid nanocarrier, fabricated through a single process using
      biomimetic mineralization. The organic scaffold (gelatin) of the fabricated
      nanocarrier is responsible for its capacity to load anionic drugs and for
      controlling the morphology of the inorganic matrix (CaCO3 ). We studied the drug
      releasing properties of the nanocarrier by investigating the response of the
      CaCO3 matrix to acidic conditions. We found that under neutral conditions, drug
      release from the nanocarrier was inhibited, whereas under acidic conditions, the
      drug was efficiently released. Therefore, drug release from the nanocarrier is
      largely dependent on the surrounding pH.

PMID- 28741845
TI  - Self-Regulation Shift Theory: A Dynamic Systems Approach to Traumatic Stress.
AB  - Self-regulation shift theory (SRST) is a threshold theory explaining self
      regulation following trauma that utilizes nonlinear dynamics to capture systemic
      shifts in trauma adaptation. Cusp catastrophe modeling tests nonlinear changes in
      an outcome (e.g., posttraumatic distress) based on an identified bifurcation
      factor under specific conditions (i.e., asymmetry variables). We evaluated two
      cusp models in a motor vehicle accident (MVA) database and then confirmed
      findings within a similar dataset. Based on SRST, we tested coping self-efficacy
      (CSE) as the bifurcation factor and a set of asymmetry controlling variables.
      Results demonstrated significant cusp models with CSE as a consistent bifurcation
      factor in all models. When participants reported lower peritraumatic
      dissociation, early lower CSE was a significant bifurcation factor for 3-month
      trauma symptoms in Sample 1, R2 = .18. The cusp model for changes in symptoms
      from 30 days to 3 months showed CSE as a significant bifurcation variable with
      higher levels of avoidant coping (R2 = .27). In a separate sample, early lower
      CSE was again a significant bifurcation variable with lower injury severity (R2 =
      .52). Results support the importance of self-regulatory appraisals in nonlinear
      shifts in posttraumatic stress symptoms 3 months post-MVA. Theoretical and
      practical implications are discussed.

PMID- 28741847
TI  - Exclusive Formation of Formic Acid from CO2 Electroreduction by a Tunable Pd-Sn
      Alloy.
AB  - Conversion of carbon dioxide (CO2 ) into fuels and chemicals by electroreduction
      has attracted significant interest, although it suffers from a large
      overpotential and low selectivity. A Pd-Sn alloy electrocatalyst was developed
      for the exclusive conversion of CO2 into formic acid in an aqueous solution. This
      catalyst showed a nearly perfect faradaic efficiency toward formic acid formation
      at the very low overpotential of -0.26 V, where both CO formation and hydrogen
      evolution were completely suppressed. Density functional theory (DFT)
      calculations suggested that the formation of the key reaction intermediate HCOO*
      as well as the product formic acid was the most favorable over the Pd-Sn alloy
      catalyst surface with an atomic composition of PdSnO2 , consistent with
      experiments.

PMID- 28741846
TI  - Confinement of Reactive Oxygen Species in an Artificial-Enzyme-Based Hollow
      Structure To Eliminate Adverse Effects of Photocatalysis on UV Filters.
AB  - Skin cancers caused by UV irradiation have been a major public health problem.
      One simple and effective way to avoid the above detrimental effects is the use of
      UV-protective sunscreens. However, there has been considerable concern with the
      issue of the production of reactive oxygen species (ROS) through the
      photodegradation of commercial UV filters. Herein, for the first time, it is
      reported that the integration of ZnO nanoparticles and CeOx nanoparticles into
      hollow microspheres (ZnO/CeOx HMS) could provide broad-spectrum UV protection and
      scavenge generated ROS under UV irradiation. Benefiting from the cooperative
      effect of the hollow structure and the antioxidative activity of CeOx , ROS
      generated under UV irradiation could be confined to a limited space and
      effectively conversion into nontoxic molecules is catalyzed as a consequence of
      increased collision frequency. Therefore, both primary, direct UV-induced damage
      and secondary ROS toxicity could be greatly reduced.

PMID- 28741848
TI  - Pharmacologic Considerations in the Management of Patients Receiving Left
      Ventricular Percutaneous Mechanical Circulatory Support.
AB  - Percutaneous mechanical circulatory support (MCS) devices, including the
      intraaortic balloon pump, Impella, and TandemHeart, are often used for
      hemodynamic support in the setting of refractory cardiogenic shock. The
      thrombotic and bleeding complications associated with these devices is well
      recognized, and the Impella and TandemHeart devices have unique anticoagulation
      considerations that may influence patient outcomes. Both devices typically
      require use of a heparinized purge solution in combination with intravenous
      unfractionated heparin, thereby providing multiple sources of heparin exposure.
      Each device also has specific monitoring requirements and goal ranges. This
      review provides an overview of percutaneous MCS devices commonly used in the
      acute management of left ventricular failure, with an emphasis on pharmacologic
      considerations. We review recent evidence and guidelines and provide
      recommendations for appropriate use of anticoagulation during device support.
      Approaches to managing heparinized purge solutions, monitoring, and the utility
      of nonheparin anticoagulants are also provided because high-quality evidence in
      the literature is limited.

PMID- 28741849
TI  - Directing the Activation of Donor-Acceptor Cyclopropanes Towards Stereoselective
      1,3-Dipolar Cycloaddition Reactions by Bronsted Base Catalysis.
AB  - The first stereoselective organocatalyzed [3+2] cycloaddition reaction of donor
      acceptor cyclopropanes is presented. It is demonstrated that by applying an
      optically active bifunctional Bronsted base catalyst, racemic di-cyano
      cyclopropylketones can be activated to undergo a stereoselective 1,3-dipolar
      reaction with mono- and polysubstituted nitroolefins. The reaction affords
      functionalized cyclopentanes with three consecutive stereocenters in high yield
      and stereoselectivity. Based on the stereochemical outcome, a mechanism in which
      the organocatalyst activates both the donor-acceptor cyclopropane and nitroolefin
      is proposed. Finally, chemoselective transformations of the cycloaddition
      products are demonstrated.

PMID- 28741850
TI  - No evidence for ecological segregation protecting native trout from invasive
      hybridization.

PMID- 28741851
TI  - Nomenclature for factors of the HLA system, update May 2017.

PMID- 28741852
TI  - Polymorphisms of miR-146a, miR-149, miR-196a2, and miR-499 are associated with
      osteoporotic vertebral compression fractures in Korean postmenopausal women.
AB  - Genetic factors have been shown to be a small but significant predictor for
      osteoporosis and osteoporotic fracture risk. We performed a case-control
      association study to determine the association between miR-146a, miR-149, miR
      196a2, and miR-499 polymorphisms and osteoporotic vertebral compression fracture
      (OVCF) susceptibility. In total, 286 unrelated postmenopausal Korean women (57
      with OVCFs, 55 with non-OVCFs, and 174 healthy controls) were recruited. All
      subjects underwent dual energy X-ray absorptiometry to determine BMD at the
      lumbar spine and femoral neck. We focused on four single nucleotide polymorphisms
      (SNPs) of pre-miRNA sequences including miR-146aC>G (rs2910164), miR-149T>C
      (rs2292832), miR-196a2T>C (rs11614913), and miR-499A>G (rs3746444). Genotype
      frequencies of these four SNPs were determined using polymerase chain reaction
      restriction fragment length polymorphism analysis. The TT genotype of miR-149aT>C
      was less frequent in subjects with OVCFs, suggesting a protective effect against
      OVCF risk (Odds ratio [OR], 0.435; 95% confidence interval [CI], 0.22-0.85, p =
      0.014), whereas the miR-146aCG/ miR-196a2TC combined genotype was more frequent
      in OVCF patients (OR, 5.163; 95%CI, 1.057-25.21, p = 0.043), suggesting an
      increase in OVCF risk. Additionally, combinations of miR-146a, -149, -196a2, and 
      449 showed a significant association with increased prevalence of OVCFs in
      postmenopausal women. In particular, the miR-146aG/-149T/-196a2C/-449G allele
      combination was significantly associated with an increased risk of OVCF (OR,
      35.01; 95% CI, 1.919-638.6, p = 0.001). Our findings suggest that the TT genotype
      of miR-149aT>C may contribute to decreased susceptibility to OVCF in Korean
      postmenopausal women. Conversely, the miR-146aCG/ miR-196a2TC combined genotype
      and the miR-146aG/-149T/-196a2C/-449G allele combination may contribute to
      increased susceptibility to OVCF. (c) 2017 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 36:244-253, 2018.

PMID- 28741853
TI  - Application of NIR Spectroscopy Coupled with PLS Regression for Quantification of
      Total Polyphenol Contents from the Fruit and Aerial Parts of Citrullus
      colocynthis.
AB  - INTRODUCTION: Citrullus colocynthis (L.) Schrad is extensively used to treat
      diabetes, obesity, fever, cancer, amenorrhea, jaundice, leukemia, rheumatism, and
      respiratory diseases. Chemical studies have indicated the presence of several
      cucurbitacins, flavones, and other polyphenols in this plant. These phytochemical
      constituents are responsible for the interesting antioxidant and other biological
      activities of C. colocynthis. OBJECTIVE: In the present study, for the first
      time, near infrared (NIR) spectroscopy coupled with partial least square (PLS)
      regression analysis was used to quantify the polyphenolic phytochemicals of C.
      colocynthis. METHODOLOGY: The fruit and aerial parts of the C. colocynthis were
      extracted individually in methanol followed by fractionation in n-hexane,
      chloroform, ethyl acetate, n-butanol, and water. Near infrared (NIR) spectra were
      obtained in absorption mode in the wavelength range 700-2500 nm. The PLS
      regression model was then built from the obtained spectral data to quantify the
      total polyphenol contents in the selected plant samples. RESULTS: The PLS
      regression model obtained had a R2 value of 99% with a 0.98 correlationship value
      and a good prediction with a root mean square error of prediction (RMSEP) value
      of 1.89% and correlation of 0.98. These results were further confirmed through UV
      vis spectroscopy and it is found that the ethyl acetate fraction has the maximum
      value for polyphenol contents (101.7 mg/100 g; NIR, 100.4 mg/100 g; UV-vis).
      CONCLUSIONS: The polyphenolic phytochemicals of the fruit and aerial parts of C.
      colocynthis have been quantified successfully by using multivariate analysis in a
      non-destructive, economical, precise, and highly sensitive method, which uses
      very simple sample preparation. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28741854
TI  - Toward Activity Origin of Electrocatalytic Hydrogen Evolution Reaction on Carbon
      Rich Crystalline Coordination Polymers.
AB  - The fundamental understanding of electrocatalytic active sites for hydrogen
      evolution reaction (HER) is significantly important for the development of metal
      complex involved carbon electrocatalysts with low kinetic barrier. Here, the MSx
      Ny (M = Fe, Co, and Ni, x/y are 2/2, 0/4, and 4/0, respectively) active centers
      are immobilized into ladder-type, highly crystalline coordination polymers as
      model carbon-rich electrocatalysts for H2 generation in acid solution. The
      electrocatalytic HER tests reveal that the coordination of metal, sulfur, and
      nitrogen synergistically facilitates the hydrogen ad-/desorption on MSx Ny
      catalysts, leading to enhanced HER kinetics. Toward the activity origin of MS2 N2
      , the experimental and theoretical results disclose that the metal atoms are
      preferentially protonated and then the production of H2 is favored on the M?N
      active sites after a heterocoupling step involving a N-bound proton and a metal
      bound hydride. Moreover, the tuning of the metal centers in MS2 N2 leads to the
      HER performance in the order of FeS2 N2 > CoS2 N2 > NiS2 N2 . Thus, the
      understanding of the catalytic active sites provides strategies for the
      enhancement of the electrocatalytic activity by tailoring the ligands and metal
      centers to the desired function.

PMID- 28741855
TI  - In Vivo Rescue of the Hematopoietic Niche By Pluripotent Stem Cell
      Complementation of Defective Osteoblast Compartments.
AB  - Bone-forming osteoblasts play critical roles in supporting bone marrow
      hematopoiesis. Pluripotent stem cells (PSCs), including embryonic stem cells
      (ESCs) and induced PSCs (iPSC), are capable of differentiating into osteoblasts.
      To determine the capacity of stem cells needed to rescue aberrant skeletal
      development and bone marrow hematopoiesis in vivo, we used a skeletal
      complementation model. Mice deficient in Runx2, a master transcription factor for
      osteoblastogenesis, fail to form a mineralized skeleton and bone marrow. Wild
      type (WT) green fluorescent protein (GFP)+ ESCs and yellow fluorescent protein
      (YFP)+ iPSCs were introduced into Runx2-null blastocyst-stage embryos. We
      assessed GFP/YFP+ cell contribution by whole-mount fluorescence and histological
      analysis and found that the proportion of PSCs in the resulting chimeric embryos
      is directly correlated with the degree of mineralization in the skull. Moreover,
      PSC contribution to long bones successfully restored bone marrow hematopoiesis.
      We validated this finding in a separate model with diphtheria toxin A-mediated
      ablation of hypertrophic chondrocytes and osteoblasts. Remarkably, chimeric
      embryos harboring as little as 37.5% WT PSCs revealed grossly normal skeletal
      morphology, suggesting a near-complete rescue of skeletogenesis. In summary, we
      demonstrate that fractional contribution of PSCs in vivo is sufficient to
      complement and reconstitute an osteoblast-deficient skeleton and hematopoietic
      marrow. Further investigation using genetically modified PSCs with conditional
      loss of gene function in osteoblasts will enable us to address the specific roles
      of signaling mediators to regulate bone formation and hematopoietic niches in
      vivo. Stem Cells 2017;35:2150-2159.

PMID- 28741856
TI  - Relationship between vitamin D and gestational diabetes in overweight or obese
      pregnant women may be mediated by adiponectin.
AB  - SCOPE: Maternal vitamin D deficiency has been implicated in adverse pregnancy
      outcomes. However, the association between vitamin D and inflammation,
      particularly adipokines, remains unexplored in pregnancy. METHODS AND RESULTS: In
      102 overweight or obese pregnant women at high-risk of gestational diabetes
      mellitus (GDM), we investigated relationships between maternal 25-hydroxyvitamin
      D (25(OH)D) concentrations at 12-15 wk gestation (baseline) and serum lipids,
      inflammatory markers, novel adipokines (omentin-1, visfatin, high molecular
      weight (HMW) adiponectin), and subsequent pregnancy outcomes (GDM, preeclampsia,
      preterm birth [PTB]). After adjustment for maternal factors (age, BMI, parity,
      ethnicity, and smoking status), baseline 25(OH)D concentrations were inversely
      associated with total cholesterol and triglycerides, and positively associated
      with HMW-adiponectin. Higher baseline 25(OH)D concentrations were associated with
      decreased fasting and 1-h post-OGTT glucose and reduced risk of GDM at 26-28 wk,
      as well as with longer gestation and reduced risk of PTB upon additional
      adjustment for caesarean section. Adding HMW-adiponectin to the multivariable
      models attenuated most associations, and HMW-adiponectin was a significant
      predictor in the models. CONCLUSION: Our findings suggest that lower maternal
      25(OH)D concentrations in overweight/obese pregnant women at high-risk of GDM are
      associated with increased cardiometabolic risks during pregnancy and adverse
      pregnancy outcomes, and that these associations may be mediated by HMW
      adiponectin.

PMID- 28741857
TI  - Surface cross-linked ultra high molecular weight polyethylene by emulsified
      diffusion of dicumyl peroxide.
AB  - Cross-linking improves the wear resistance of ultrahigh molecular weight
      polyethylene (UHMWPE) used in hip and knee implants. Free radicals, generated by
      ionizing radiation or chemically, react to form cross-links. Limiting cross
      linking to the articulating surface of the implant is desirable to enable high
      wear resistance on the surface and higher strength and toughness in the bulk. We
      investigated the diffusion of emulsified dicumyl peroxide (DCP) into vitamin E
      blended UHMWPE (0.1 and 0.3 wt. % vitamin-E) with subsequent thermal
      decomposition in situ to obtain surface cross-linking with the objective of
      achieving surface wear rate equivalent or lower than that of current clinically
      available materials. We diffused emulsified DCP at 100 degrees C followed by in
      situ decomposition at 150 degrees C. We also assessed the effect of having
      vitamin-E in the DCP emulsion. The oxidative stability of the treated samples
      increased with increasing vitamin E concentration in the blend and by
      incorporating vitamin E into the peroxide emulsion. The impact strength of a
      surface cross-linked, 0.3 wt% vitamin E blended UHMWPE prepared using this method
      was superior to a clinically available irradiated and melted highly cross-linked
      UHMWPE while the wear resistance was comparable. These results showed the
      feasibility of surface cross-linking using emulsified peroxide diffusion as a
      method of making tough and wear resistant joint implant bearing surfaces. (c)
      2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1517
      1523, 2018.

PMID- 28741858
TI  - A computational approach for inferring the cell wall properties that govern guard
      cell dynamics.
AB  - Guard cells dynamically adjust their shape in order to regulate photosynthetic
      gas exchange, respiration rates and defend against pathogen entry. Cell shape
      changes are determined by the interplay of cell wall material properties and
      turgor pressure. To investigate this relationship between turgor pressure, cell
      wall properties and cell shape, we focused on kidney-shaped stomata and developed
      a biomechanical model of a guard cell pair. Treating the cell wall as a composite
      of the pectin-rich cell wall matrix embedded with cellulose microfibrils, we show
      that strong, circumferentially oriented fibres are critical for opening. We find
      that the opening dynamics are dictated by the mechanical stress response of the
      cell wall matrix, and as the turgor rises, the pectinaceous matrix stiffens. We
      validate these predictions with stomatal opening experiments in selected
      Arabidopsis cell wall mutants. Thus, using a computational framework that
      combines a 3D biomechanical model with parameter optimization, we demonstrate how
      to exploit subtle shape changes to infer cell wall material properties. Our
      findings reveal that proper stomatal dynamics are built on two key properties of
      the cell wall, namely anisotropy in the form of hoop reinforcement and strain
      stiffening.

PMID- 28741859
TI  - Inpatient palliative care referral and 9-month hospital readmission in patients
      with congestive heart failure: a linked nationwide analysis.
AB  - OBJECTIVE: End-stage heart failure (HF) is characterized by high symptom burden
      and frequent hospitalization. Palliative care (PC) is recommended for advanced
      HF, and there is some evidence in other diseases that this may reduce readmission
      rates. We attempted examine the association of an inpatient PC visit on hospital
      readmission for patients admitted with HF. METHODS: Retrospective linked
      nationwide analysis from 2013 with 9-month follow-up for all hospital
      readmissions for patients admitted with HF exacerbations using the Nationwide
      Readmission Database (NRD). The NRD gathers all hospital admissions for patients
      from 22 states and tracks patients throughout the year, allowing for examination
      of readmission statistics. A propensity score model for PC visit was made, and
      patients were matched in a 1 : 1 fashion. RESULTS: There were 102 746 patients
      who survived an admission for HF in the first 3 months of 2013. Of these, 2287
      (2.2%) patients had a PC visit as inpatients. After matching based on propensity
      for a PC visit during the index hospitalization, 2282 patients who received a PC
      visit were matched to 2282 patients who did not. Those receiving a PC visit were
      less likely to be readmitted for HF (9.3% vs. 22.4%, P < 0.01) or for any cause
      (29.0% vs. 63.2%, P < 0.01) during the 9-month follow-up period. The average
      hospital charges during the follow-up period for the non-PC cohort were $77 643
      per patient. The average charges for PC patients were $23 200 (P < 0.01).
      CONCLUSIONS: Patients with HF who received an inpatient PC visit had
      significantly lower rates of all-cause and HF-specific readmission in the
      subsequent 9 months. Total 9-month hospital charges were also significantly lower
      for patients who received an inpatient PC visit.

PMID- 28741860
TI  - Autoinducer Sensing Microarrays by Reporter Bacteria Encapsulated in Hybrid
      Supramolecular-Polysaccharide Hydrogels.
AB  - A generally applicable strategy to obtain mechanically robust hydrogels for the
      incorporation and containment of functional reporter bacteria for the microarray
      and microparticle-based detection and signaling of N-acyl homoserine lactone
      autoinducers (3OC12 HSL) at relevant concentrations is reported. For reinforcing
      hydrogels of 1,4-bi(phenylalanine-diglycol)-benzene (PDB), a hybrid hydrogel is
      formed by the combination of PDB self-assembly with Ca2+ mediated alginate
      crosslinking. The different assembly mechanisms are shown not to interfere with
      each other and despite the more than four-fold increased moduli of the hydrogels,
      diffusion of autoinducers into the gels remains efficient and Escherichia coli
      pLuxR-green fluorescent protein (GFP) reporter bacteria are proliferating.
      Templating affords reporter bacteria-loaded hydrogels with controllable shape and
      size. Upon exposure to 3OC12 HSL, the embedded bacteria exhibit an up to 12 +/- 3
      times increase in fluorescence intensity due to autoinducer-triggered GFP
      expression. This approach can serve as a potentially generally applicable
      strategy to sensitively detect bacteria via their secreted autoinducers.

PMID- 28741861
TI  - Parvularia atlantis gen. et sp. nov., a Nucleariid Filose Amoeba (Holomycota,
      Opisthokonta).
AB  - The opisthokonts constitute a eukaryotic supergroup divided into two main clades:
      the holozoans, which include animals and their unicellular relatives, and the
      holomycotans, which include fungi, opisthosporidians, and nucleariids.
      Nucleariids are phagotrophic filose amoebae that phenotypically resemble more
      their distant holozoan cousins than their holomycotan phylogenetic relatives.
      Despite their evolutionary interest, the diversity and internal phylogenetic
      relationships within the nucleariids remain poorly studied. Here, we formally
      describe and characterize by molecular phylogeny and microscopy observations
      Parvularia atlantis gen. et sp. nov. (formerly Nuclearia sp. ATCC 50694), and
      compare its features with those of other nucleariid genera. Parvularia is an
      amoebal genus characterized by radiating knobbed and branching filopodia. It
      exhibits prominent vacuoles observable under light microscopy, a cyst-like stage,
      and completely lacks cilia. P. atlantis possesses one or two nuclei with a
      central nucleolus, and mitochondria with flat or discoid cristae. These
      morphological features, although typical of nucleariids, represent a combination
      of characters different to those of any other described Nuclearia species.
      Likewise, 18S rRNA-based phylogenetic analyses show that P. atlantis represents a
      distinct lineage within the nucleariids.

PMID- 28741862
TI  - In vivo comparison of jellyfish and bovine collagen sponges as prototype medical
      devices.
AB  - Jellyfish have emerged as a source of next generation collagen that is an
      attractive alternative to existing sources, such as bovine and porcine, due to a
      plentiful supply and providing a safer source through lack of bovine spongiform
      encephalopathy (BSE) transmission risk and potential viral vectors, both of which
      could be transmitted to humans. Here we compare collagen implantable sponges
      derived for the first time from the Rhizostoma pulmo jellyfish. A further novelty
      for the research was that there was a comparison for sponges that were either
      uncrosslinked or crosslinked using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
      hydrochloride (EDC), and an assessment on how this affected resorption, as well
      as their biocompatibility compared to bovine type I collagen sponges. The
      scaffolds were prepared and examined using sodium dodecyl sulfate polyacrylamide
      gel electrophoresis (SDS PAGE) and scanning electron microscopy (SEM). The
      samples were implanted in adult male Wistar rats for in vivo experimentation.
      Both crosslinked and uncrosslinked jellyfish collagen sponges showed a
      significant reduction in histopathology scores over the course of the study,
      whereas the bovine collagen sponge scores were not significantly reduced. Both
      jellyfish collagen sponges and the bovine sponge were tolerated well by the
      hosts, and a recovery was visible in all samples, suggesting that R. pulmo
      jellyfish-derived collagen could offer compelling biocompatibility with wound
      healing applications. We also demonstrate that noncrosslinked samples could be
      safer with better resorption times than crosslinked samples. (c) 2017 The Authors
      Journal of Biomedical Materials Research Part B: Applied Biomaterials Published
      by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1524
      1533, 2018.

PMID- 28741863
TI  - Development of quality metrics for ambulatory pediatric cardiology: Infection
      prevention.
AB  - INTRODUCTION: In 2012, the American College of Cardiology's (ACC) Adult
      Congenital and Pediatric Cardiology Council established a program to develop
      quality metrics to guide ambulatory practices for pediatric cardiology. The
      council chose five areas on which to focus their efforts; chest pain, Kawasaki
      Disease, tetralogy of Fallot, transposition of the great arteries after arterial
      switch, and infection prevention. Here, we sought to describe the process,
      evaluation, and results of the Infection Prevention Committee's metric design
      process. METHODS: The infection prevention metrics team consisted of 12 members
      from 11 institutions in North America. The group agreed to work on specific
      infection prevention topics including antibiotic prophylaxis for endocarditis,
      rheumatic fever, and asplenia/hyposplenism; influenza vaccination and respiratory
      syncytial virus prophylaxis (palivizumab); preoperative methods to reduce
      intraoperative infections; vaccinations after cardiopulmonary bypass; hand
      hygiene; and testing to identify splenic function in patients with heterotaxy. An
      extensive literature review was performed. When available, previously published
      guidelines were used fully in determining metrics. RESULTS: The committee chose
      eight metrics to submit to the ACC Quality Metric Expert Panel for review.
      Ultimately, metrics regarding hand hygiene and influenza vaccination
      recommendation for patients did not pass the RAND analysis. Both endocarditis
      prophylaxis metrics and the RSV/palivizumab metric passed the RAND analysis but
      fell out during the open comment period. Three metrics passed all analyses,
      including those for antibiotic prophylaxis in patients with heterotaxy/asplenia,
      for influenza vaccination compliance in healthcare personnel, and for adherence
      to recommended regimens of secondary prevention of rheumatic fever. CONCLUSIONS:
      The lack of convincing data to guide quality improvement initiatives in pediatric
      cardiology is widespread, particularly in infection prevention. Despite this,
      three metrics were able to be developed for use in the ACC's quality efforts for
      ambulatory practice.

PMID- 28741864
TI  - Pseudocapacitive Desalination of Brackish Water and Seawater with Vanadium
      Pentoxide-Decorated Multiwalled Carbon Nanotubes.
AB  - A hybrid membrane pseudocapacitive deionization (MPDI) system consisting of a
      hydrated vanadium pentoxide (hV2 O5 )-decorated multi-walled carbon nanotube
      (MWCNT) electrode and one activated carbon electrode enables sodium ions to be
      removed by pseudocapacitive intercalation with the MWCNT-hV2 O5 electrode and
      chloride ion to be removed by non-faradaic electrosorption of the porous carbon
      electrode. The MWCNT-hV2 O5 electrode was synthesized by electrochemical
      deposition of hydrated vanadium pentoxide on the MWCNT paper. The stable
      electrochemical operating window for the MWCNT-hV2 O5 electrode was between -0.5
      V and +0.4 V versus Ag/AgCl, which provided a specific capacity of 44 mAh g-1
      (corresponding with 244 F g-1 ) in aqueous 1 m NaCl. The desalination performance
      of the MPDI system was investigated in aqueous 200 mm NaCl (brackish water) and
      600 mm NaCl (seawater) solutions. With the aid of an anion and a cation exchange
      membrane, the MPDI hybrid cell was operated from -0.4 to +0.8 V cell voltage
      without crossing the reduction and oxidation potential limit of both electrodes.
      For the 600 mm NaCl solution, the NaCl salt adsorption capacity of the cell was
      23.6+/-2.2 mg g-1 , which is equivalent to 35.7+/-3.3 mg g-1 normalized to the
      mass of the MWCNT-hV2 O5 electrode. Additionally, we propose a normalization
      method for the electrode material with faradaic reactions based on sodium uptake
      capacities.

PMID- 28741865
TI  - Nomenclature for factors of the HLA system, update April 2017.

PMID- 28741866
TI  - A review of available laser and intense light source home devices: A
      dermatologist's perspective.
AB  - BACKGROUND: Home optical devices are becoming an increasingly popular treatment
      modality sought out by patients for dermatologic pathologies such as acne, hair
      removal and anti-aging, as these devices are a low-cost and convenient therapy
      choice. METHODS: An Internet search using PubMed.gov was completed with search
      terms, "home device dermatology," "home device acne," "home device hair" or "hair
      removal," and "home device aging." RESULTS: Currently, there are multiple home
      optical devices available on the market. These devices have been approved for the
      treatment of acne, scars, hair removal, and wrinkles using intense pulsed light,
      light-emitting diode, heat, infrared, low-level light therapy, and laser.
      Although studies on home devices are limited, current dermatologic literature
      shows that these devices are promising with significant post-treatment results as
      well as a high level of safety. CONCLUSIONS: Home optical devices are mostly used
      without medical practitioner supervision. As home devices usually deliver less
      energy per session than with professional treatments, it is important that
      consumers are given realistic expectations of post-treatment outcomes. Patients
      may use home devices without disclosure to their physician and it is important as
      healthcare professionals to be aware of the existence of these devices, how to
      use the devices properly (including what diseases can be treated and which skin
      types are considered safe for use), as well as any adverse effects that may
      occur. New research endeavors are being completed to explore the used of home
      devices for the treatment of chronic inflammatory diseases such as psoriasis.

PMID- 28741867
TI  - Targeting of a Helix-Loop-Helix Transcriptional Regulator by a Short Helical
      Peptide.
AB  - The Id proteins (Id1-4) are cell-cycle regulators that play a key role during
      development, in cancer and vascular disorders. They contain a conserved helix
      loop-helix (HLH) domain that folds into a parallel four-helix bundle upon self-
      or hetero-association with basic-HLH transcription factors. By using such protein
      protein interactions, the Id proteins inhibit cell differentiation and promote
      cell-cycle progression. Accordingly, their supporting role in cancer has been
      convincingly demonstrated, which makes these proteins interesting therapeutic
      targets. Herein we present a short peptide containing an (i,i+4)-lactam bridge
      and a hydrophobic (Phi) three-residue motif Phi(i)-Phi(i+3)-Phi(i+6), which
      adopts a helical conformation in water, shows Id protein binding in the low
      micromolar range, penetrates into breast (MCF-7 and T47D) and bladder (T24)
      cancer cells, accumulates in the nucleus, and decreases cell viability to ~50 %.
      Thus, this cyclopeptide is a promising scaffold for the development of Id protein
      binders that impair cancer cell viability.

PMID- 28741868
TI  - Retrospective analysis of the efficacy and safety of eribulin therapy for
      metastatic breast cancer in daily practice.
AB  - BACKGROUND: Evidence of eribulin therapy for metastatic breast cancer (MBC) in
      clinical practice is not well documented. METHODS: We retrospectively analyzed
      the safety and efficacy of eribulin in 29 MBC patients from 2011 to 2016 at
      Fukuoka University Hospital. RESULTS: The median patient age, number of courses,
      total dose, and relative dose intensity were as follows: 65 years, five courses,
      8.6 mg/m2 , and 75%, respectively. One patient achieved a complete response, (CR)
      six a partial response (PR), eight stable disease (SD) and 14 patients exhibited
      progressive disease. The objective response rate (ORR: CR + PR) was 24.1%, and
      the clinical benefit rate (CBR: CR + PR + SD) was 51.7%. The median progression
      free survival was 90 days (95% confidence interval [CI] 67-126) and median
      overall survival was 264 days (95% CI 198-357). In patients who previously
      received 2-4 regimens, the ORR was 28.5% and the CBR was 57.1%. In patients who
      received 5-12 regimens, the ORR was 20% and the CBR was 45%. Chemotherapy was
      administered to 20 patients (69%) after eribulin administration, and the median
      overall survival rate of cases that achieved greater than a PR was 1088 days. The
      most frequent treatment-related grade 3/4 adverse events were neutropenia
      (55.2%), and febrile neutropenia (20.1%). Grade 3 peripheral neuropathy occurred
      in 13.8% of patients, but was not exacerbated even if present before treatment.
      CONCLUSION: Eribulin is effective for MBC patients who have received multiple
      chemotherapies. Neutropenia and febrile neutropenia may develop after heavy prior
      therapy.

PMID- 28741869
TI  - Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral
      blood of disease-modifying anti-rheumatic drug-naive rheumatoid arthritis
      patients are associated with improved clinical response to methotrexate therapy.
AB  - OBJECTIVE: To investigate the potential of the baseline gene expression in the
      whole blood of disease-modifying anti-rheumatic drug-naive rheumatoid arthritis
      (RA) patients for predicting the response to methotrexate (MTX) treatment.
      METHODS: Twenty-six control subjects and 40 RA patients were examined. Clinical,
      immunological and radiographic parameters were assessed before and after 24
      months of follow-up. The gene expressions in the whole blood were measured using
      real-time reverse transcription polymerase chain reaction. The protein
      concentrations in peripheral blood mononuclear cells were quantified using enzyme
      linked immunosorbent assay. Receiver operating characteristic curve analyses were
      used to suggest thresholds that were associated with the prediction of the
      response. RESULTS: Decreases in the disease activity at the end of the study were
      accompanied by significant increases in joint space narrowing score (JSN).
      Positive correlations between the expressions of the Unc-51-like kinase 1 (ULK1)
      and matrix metalloproteinase 9 (MMP-9) genes with the level of C-reactive protein
      and MMP-9 expression with Disease Activity Score of 28 joints (DAS28) and swollen
      joint count were noted at baseline. The baseline tumor necrosis factor (TNF)alpha
      gene expression was positively correlated with JSN at the end of the follow-up,
      whereas p21, caspase 3, and runt-related transcription factor (RUNX)2 were
      correlated with the DeltaDAS28 values. CONCLUSIONS: Our results suggest that the
      expressions of MMP-9 and ULK1 might be associated with disease activity.
      Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral
      blood might predict better responses to MTX therapy.

PMID- 28741870
TI  - Impact of functional training on geometric indices and fractal correlation
      property of heart rate variability in postmenopausal women.
AB  - BACKGROUND: To evaluate the influence of functional training on the geometric
      indices of heart rate variability (HRV) and fractal correlation properties of the
      dynamics of heart rate in menopausal women. METHODS: Of 39 women who were in the
      period of menopause for more than a year and who did not practice any regular
      physical activity were divided into: Functional training group (FTG = 50 +/- 4.5
      years; 67.64 +/- 11.64 kg; 1.5 +/- 0.05 m) that executed the functional training
      (FT) and all proposals by reviews and the Control group (58.45 +/- 4.8 years;
      66.91 +/- 13.24 kg; 1.55 +/- 0.05 m) who performed all assessments but not FT.
      The training consisted of 18 weeks (three times a week) and the volunteers
      performed three sets of 11 functional exercises followed by a walk in each of the
      sessions. The autonomic nervous system modulation was evaluated by analysis of
      HRV and the indices obtained were: RR intervals, RRTRI, TINN, SD1, SD2, SD1/SD2,
      qualitative analysis of Poincare plot and DFA (alfa-1, alfa-2 and alfa-1/alfa-2).
      The Student's t-test for unpaired samples (normal data) or Mann-Whitney test
      nonnormal data) were used to compare the differences obtained between the final
      moment and the initial moment of the studied groups (p < .05). CONCLUSION: Were
      observed in the FTG: increased SD1 (CG 0.13 +/- 4.00 vs. 3.60 +/- 8.43), beat-to
      beat global dispersion much greater as an increased in the dispersion of long
      term RR intervals and increased fractal properties of short-term (alpha1) (CG 
      0.04 +/- 0.13 vs. 0.07 +/- 0.21). FT promoted a beneficial impact on cardiac
      autonomic modulation, characterized by increased parasympathetic activity and
      short-term fractal properties of the dynamics of the heart rate.

PMID- 28741871
TI  - Pharmacodynamics, pharmacokinetics, safety and tolerability of the novel dual
      glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist
      RG7697 after single subcutaneous administration in healthy subjects.
AB  - AIMS: To evaluate the pharmacodynamics, pharmacokinetics and safety of single
      subcutaneous (s.c.) injection of ascending doses of RG7697, a dual glucose
      dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist, in healthy
      subjects. METHODS: A total of 51 healthy volunteers were enrolled in this double
      blind, placebo-controlled study investigating RG7697 doses ranging from 0.03 to 5
      mg. Adverse events (AEs) were monitored and drug concentrations, fasting
      glycaemic variables, vital signs, ECG, antibody formation and routine laboratory
      variables were assessed. A meal tolerance test (MTT) was performed at the same
      time on day -1 (baseline) and day 1. RESULTS: RG7697 was generally well tolerated
      in healthy participants after s.c. injections up to 3.6 mg. Tolerability was
      limited by gastrointestinal AEs (nausea and vomiting) at the highest dose. There
      was a small dose-dependent increase in heart rate. No episodes of hypoglycaemia
      occurred. RG7697 concentrations peaked at 2 to 4 hours post-dose with a half-life
      of 19 to 25 hours. During MTT, RG7697 at doses >=1.8 mg, reduced glucose maximum
      plasma concentration (Cmax ; -46%) without affecting overall glucose area under
      the curve (AUC). Its effect on insulin was more pronounced, with reductions in
      both Cmax (-64%) and AUC (-51%). Pharmacodynamic variables were well correlated
      to RG7697 average plasma concentration during MTT, with IC50 (average
      concentration required for 50% reduction) values of 49 and 24.5 ng/mL for glucose
      and insulin, respectively. CONCLUSION: Single s.c. injections of RG7697 up to 3.6
      mg were generally well tolerated. Evidence of glycaemic effect and
      pharmacokinetic profiles consistent with once-daily dosing render this drug
      candidate suitable to be further tested in multiple-dose clinical trials in
      patients with type 2 diabetes.

PMID- 28741872
TI  - Breast disease in men in metropolitan Sao Paulo - Brazil.
AB  - Although rare, breast cancer in males represents 1% of all cancer in men, and has
      shown increasing incidence in 25 years. To analyze age, gender, type of procedure
      performed and diagnosis of all cases of breast diseases in a public hospital in
      Sao Paulo, Brazil, with special focus on men. Cross-sectional study of breast
      surgery in 2010-2014 at Hospital Municipal Universitario de Sao Bernardo do
      Campo, Brazil. In the period 999 breast surgery were carried out. Patients with
      benign diseases were about 30 years old and patients with malignant diseases were
      over 50. Most surgical procedures performed on men were on the benign condition
      of gynaecomastia (n=21). The prevalence of breast cancer in the male population
      attending the public health system in Sao Bernardo was 0.27 (per 100,000). There
      was a single record of malignant disease in men, a 65 years old man, with
      histological diagnosis of ductal carcinoma. Surgical pathology of the breast in
      men is a rare event, and accounts for about 2.4% of mammary surgery in the
      municipality of Sao Bernardo do Campo. Awareness is necessary for health
      professionals and the media, regarding breast pathologies in the male population,
      to reduce the prejudice in the search for an early diagnosis of a condition so
      strongly linked to the female for the majority of people.

PMID- 28741873
TI  - Cost-effectiveness of left ventricular assist devices for patients with end-stage
      heart failure: analysis of the French hospital discharge database.
AB  - AIMS: Although left ventricular assist devices (LVADs) are currently approved for
      coverage and reimbursement in France, no French cost-effectiveness (CE) data are
      available to support this decision. This study aimed at estimating the CE of LVAD
      compared with medical management in the French health system. METHODS AND
      RESULTS: Individual patient data from the 'French hospital discharge database'
      (Medicalization of information systems program) were analysed using Kaplan-Meier
      method. Outcomes were time to death, time to heart transplantation (HTx), and
      time to death after HTx. A micro-costing method was used to calculate the monthly
      costs extracted from the Program for the Medicalization of Information Systems. A
      multistate Markov monthly cycle model was developed to assess CE. The analysis
      over a lifetime horizon was performed from the perspective of the French
      healthcare payer; discount rates were 4%. Probabilistic and deterministic
      sensitivity analyses were performed. Outcomes were quality-adjusted life years
      (QALYs) and incremental CE ratio (ICER). Mean QALY for an LVAD patient was 1.5 at
      a lifetime cost of ?190 739, delivering a probabilistic ICER of ?125 580/QALY
      [95% confidence interval: 105 587 to 150 314]. The sensitivity analysis showed
      that the ICER was mainly sensitive to two factors: (i) the high acquisition cost
      of the device and (ii) the device performance in terms of patient survival.
      CONCLUSIONS: Our economic evaluation showed that the use of LVAD in patients with
      end-stage heart failure yields greater benefit in terms of survival than medical
      management at an extra lifetime cost exceeding the ?100 000/QALY. Technological
      advances and device costs reduction shall hence lead to an improvement in overall
      CE.

PMID- 28741874
TI  - Alcohol consumption trends in Australia: Comparing surveys and sales-based
      measures.
AB  - INTRODUCTION AND AIMS: Survey data remain a crucial means for monitoring alcohol
      consumption, but there has been limited work done to ensure that surveys
      adequately capture changes in per-capita consumption in Australia. In this study,
      we explore how trends in consumption from two major Australian surveys compare
      with an official measure of per-capita consumption between 2001 and 2014 and
      examine age-specific trends in drinking. DESIGN AND METHODS: Data were from five
      waves of the cross-sectional National Health Survey (total n = 113 279) and 12
      waves of the longitudinal Household Income and Labour Dynamics in Australia Study
      (average n = 12 347). Overall and age-specific estimates of annual alcohol
      consumption were derived and compared with official per-capita consumption and
      previous analyses of the National Drug Strategy Household Survey. RESULTS: In
      terms of overall consumption, both surveys broadly reflected trends in per-capita
      consumption, especially the decline that has been observed since 2007/2008. Age
      specific trends were broadly similar, with the recent decline in consumption
      clearly concentrated among teenagers and young adults. DISCUSSION AND
      CONCLUSIONS: The main Australian monitoring surveys remain useful monitoring
      tools for alcohol consumption in Australia. There is consistent evidence that the
      recent declines in Australian per-capita consumption have been driven by sharp
      falls in drinking among young people, a trend that requires further study.
      [Livingston M, Callinan S, Raninen J, Pennay A, Dietze PM. Alcohol consumption
      trends in Australia: Comparing surveys and sales-based measures. Drug Alcohol Rev
      2017;00:000-000].

PMID- 28741875
TI  - Depression and Anxiety Among Emergency Department Patients: Utilization and
      Barriers to Care.
AB  - BACKGROUND: Anxiety and depression rates among emergency department (ED) patients
      are substantially higher than those in the general population. Additionally,
      those with mental health issues often have difficulty accessing care.
      Unfortunately, issues of anxiety and depression are frequently not addressed in
      the ED due to competing care priorities. This may lead to increased burden and
      overcrowding in EDs. OBJECTIVE: This study related anxiety and depression with ED
      utilization and perceived barriers to care. METHODS: To limit the impact of
      insurance coverage on ED utilization and access to care, a convenience sample of
      adults 45 to 85 years of age in the ED were surveyed. The Generalized Anxiety
      Disorder 7 and Patient Health Questionnaire 9 were used to measure anxiety and
      depression. RESULTS: A total of 251 subjects were enrolled. Severe anxiety was
      observed in 10% of patients, while moderately severe or severe depression was
      observed in 12%. Patients who were both severely anxious and depressed visited
      the ED nearly twice as often as nonanxious and nondepressed patients. The
      majority of patients cited at least one moderate barrier to care, and greater
      anxiety and depression scores were related to greater perceived barriers to care.
      Perceived barriers to care were more than three times higher among patients who
      were both anxious and depressed compared to those in patients who were neither
      depressed nor anxious and twice as high as in those who were either depressed or
      anxious (p < 0.001). CONCLUSION: Patients identified with internalizing mental
      health concerns utilize the ED at elevated rates while also reporting the
      greatest difficulties accessing care. These findings highlight the need for ED
      interventions aimed at identifying patient mental health concerns, as well as
      perceived barriers to care, to design interventions to effectively improve
      continuity of care.

PMID- 28741876
TI  - Discovery of Novel Potent Muscarinic M3 Receptor Antagonists with Proper Plasma
      Stability by Structural Recombination of Marketed M3 Antagonists.
AB  - The marketed long-acting M3 antagonists for treatment of chronic obstructive
      pulmonary disease have inappropriate plasma stability (either overstable or
      excessively unstable), which causes substantial systemic exposure or poor patient
      compliance. To discover novel M3 antagonists with proper plasma stability, we
      synthesized and biologically evaluated a series of chiral quaternary ammonium
      salts of pyrrolidinol esters, which were designed by structural recombination of
      the marketed M3 antagonists. As a result, two novel potent M3 antagonists, (R/S)
      3-[2-hydroxy-2,2-di(thiophen-2-yl)acetoxy]-1,1-dimethylpyrrolidinium bromides (1
      a: Ki =0.16 nm, IC50 =0.38 nm, t1/2 =9.34 min; 1 b: Ki =0.32 nm, IC50 =1.01 nm,
      t1/2 =19.2 min) with proper plasma stability were identified, which (particularly
      1 a) hold great promise as clinical drug candidates to overcome the drawbacks
      caused by the inappropriate stability of the currently marketed M3 antagonists.
      In addition, structure-activity relationship studies revealed that the R
      configuration of the pyrrolidinyl C3 atom was clearly better than the S
      configuration.

PMID- 28741877
TI  - Boy with short stature and joint pains.

PMID- 28741878
TI  - Anticancer Gold N-Heterocyclic Carbene Complexes: A Comparative in vitro and ex
      vivo Study.
AB  - A series of organometallic AuI N-heterocyclic carbene (NHC) complexes was
      synthesized and characterized for anticancer activity in four human cancer cell
      lines. The compounds' toxicity in healthy tissue was determined using precision
      cut kidney slices (PCKS) as a tool to determine the potential selectivity of the
      gold complexes ex vivo. All evaluated compounds presented cytotoxic activity
      toward the cancer cells in the nano- or low micromolar range. The mixed AuI NHC
      complex, (tert-butylethynyl)-1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene
      gold(I), bearing an alkynyl moiety as ancillary ligand, showed high cytotoxicity
      in cancer cells in vitro, while being barely toxic in healthy rat kidney tissues.
      The obtained results open new perspectives toward the design of mixed NHC-alkynyl
      gold complexes for cancer therapy.

PMID- 28741879
TI  - MiR-376a suppresses the proliferation and invasion of non-small-cell lung cancer
      by targeting c-Myc.
AB  - It has been reported that miR-376a is involved in the formation and progression
      of several types of cancer. However, the expression and function of miR-376a is
      still unknown in non-small cell lung carcinomas (NSCLC). In this study, the
      expression of miR-376a in NSCLC tissues and cell lines were examined by real-time
      PCR, the effects of miR-376a on cell proliferation, apoptosis and invasion were
      evaluated in vitro. Luciferase reporter assay was performed to identify the
      targets of miR-376a. The results showed that miR-376a was significantly
      downregulated in NSCLC tissues and cell lines. Restoration of miR-376a in NSCLC
      cell line A549 significantly inhibited cell proliferation, increased cell
      apoptosis and suppressed cell invasion, compared with control-transfected A549
      cells. Luciferase reporter assay showed that c-Myc, an oncogene that regulating
      cell survival, angiogenesis and metastasis, was a direct target of miR-376a. Over
      expression of miR-376a decreased the mRNA and protein levels of c-Myc in A549
      cells. In addition, upregulation of c-Myc inhibited miR-376a-induced inhibition
      of cell proliferation and invasion in A549 cells. Therefore, our results indicate
      a tumor suppressor role of miR-376a in NSCLC by targeting c-Myc. miR-376a may be
      a promising therapeutic target for NSCLC.

PMID- 28741880
TI  - Towards Extending Solar Cell Lifetimes: Addition of a Fluorous Cation to Triple
      Cation-Based Perovskite Films.
AB  - Organohalide perovskites have emerged as highly promising replacements for thin
      film solar cells. However, their poor stability under ambient conditions remains
      problematic, hindering commercial exploitation. The addition of a fluorous
      functionalized imidazolium cation during the preparation of a highly stable
      cesium-based mixed perovskite material Cs0.05 (MA0.15 FA0.85 )0.95 Pb(I0.85
      Br0.15 )3 (MA=methylammonium; FA=formamidinium) has been shown to influence its
      stability. The resulting materials, which vary according to the amount of the
      fluorous-functionalized imidazolium cation present during fabrication, display a
      prolonged tolerance to atmospheric humidity (>100 days) along with power
      conversion efficiencies exceeding 16 %. This work provides a general route that
      can be implemented in a variety of perovskites and highlights a promising way to
      increase perovskite solar cell stability.

PMID- 28741882
TI  - Expression of plakoglobin in the myocardium was reduced in an elderly patient
      with arrhythmogenic right ventricular cardiomyopathy.

PMID- 28741881
TI  - Nomenclature for factors of the HLA system, update June 2017.

PMID- 28741883
TI  - Clock-drawing test for cognitive assessment in an older adult with long-term
      benzodiazepine use.

PMID- 28741884
TI  - Prevalence of false positive troponin I in elderly patients with rhabdomyolysis.

PMID- 28741885
TI  - Chylothorax ascribed to chronic heart failure in a woman of very advanced years.

PMID- 28741886
TI  - Synthesis of Polyfunctional Diorganomagnesium and Diorganozinc Reagents through
      In Situ Trapping Halogen-Lithium Exchange of Highly Functionalized (Hetero)aryl
      Halides in Continuous Flow.
AB  - We report a halogen-lithium exchange performed in the presence of various metal
      salts (ZnCl2 , MgCl2 ?LiCl) on a broad range of sensitive bromo- or
      iodo(hetero)arenes using BuLi or PhLi as the exchange reagent and a commercially
      available continuous-flow setup. The resulting diarylmagnesium or diarylzinc
      species were trapped with various electrophiles, resulting in the formation of
      polyfunctional (hetero)arenes in high yields. This method enables the
      functionalization of (hetero)arenes containing highly sensitive groups such as an
      isothiocyanate, nitro, azide, or ester. A straightforward scale-up was possible
      without further optimization.

PMID- 28741887
TI  - Linac-based stereotactic radiation therapy for canine non-lymphomatous nasal
      tumours: 29 cases (2013-2016).
AB  - Twenty-nine dogs were treated with linac-based stereotactic radiation therapy
      (SRT) for non-lymphomatous nasal tumours. Only dogs with a follow-up time >365
      days were included in this retrospective analysis. No dogs had evidence of
      distant metastasis at diagnosis. Treatment was planned and a total of 30 Gy in 3
      daily 10 Gy fractions was delivered using intensity-modulation, cone-beam CT
      based image guidance and a robotic treatment couch. Clinical signs improved in
      all cases. Nineteen dogs had CT scans 3-4 months post-SRT and all had partial or
      complete tumour response. Minimal acute toxicities were detected. Clinically
      significant late toxicities included oronasal or nasocutaneous fistulas (N = 3)
      and biopsy-confirmed fungal rhinitis with no evidence of tumour progression (N =
      2). The median progression-free survival (PFS) was 354 days, with 49% and 39%
      progression-free at 1 and 2 years post-SRT, respectively. The median survival
      time (ST) was 586 days, with 69% and 22% alive 1 and 2 years post-SRT,
      respectively. Neither the clinical parameters evaluated (modified Adams' stage,
      histopathology, presence of intracranial extension of the tumour) nor dosimetric
      data were predictive for PFS or ST. This SRT protocol appears to be well
      tolerated, and PFI and ST are comparable or superior to those reported in other
      definitive-intent radiotherapy protocols.

PMID- 28741888
TI  - beta-Lactam Synthesis through Diodomethane Addition to Amide Dianions.
AB  - We present a novel route for the quick and easy synthesis of a broad range of
      beta-lactams. The synthesis involves a [3+1] cyclization of amide dianions with
      diiodomethane. In contrast to the seminal work of Hirai et al. from 1979, the
      reaction proved to be a general and efficient approach towards azetidinones. The
      ease of the process was confirmed by DFT calculations and its power demonstrated
      by a diversity-oriented synthesis of beta-lactams with four points of diversity
      determined by the choice of Ugi adducts as starting materials.

PMID- 28741889
TI  - Reply to Rana Nadeem's Letter to the Editor.

PMID- 28741890
TI  - Nucleophilic Amination of Methoxy Arenes Promoted by a Sodium Hydride/Iodide
      Composite.
AB  - A method for the nucleophilic amination of methoxy arenes was established by
      using sodium hydride (NaH) in the presence of lithium iodide (LiI). This method
      offers an efficient route to benzannulated nitrogen heterocycles. Mechanistic
      studies showed that the reaction proceeds through an unusual concerted
      nucleophilic aromatic substitution.

PMID- 28741891
TI  - Children with refractory ARDS.

PMID- 28741892
TI  - Dose comparison between Gafchromic film, XiO, and Monaco treatment planning
      systems in a novel pelvic phantom that contains a titanium hip prosthesis.
AB  - The presence of metallic prostheses during external beam radiotherapy of
      malignancies in the pelvic region has the potential to strongly influence the
      dose distribution to the target and to tissue surrounded by the prostheses. This
      study systematically investigates the perturbation effects of unilateral titanium
      prosthesis on 6 and 15 MV photon beam dose distributions using Gafchromic EBT2
      film measurements in a novel pelvic phantom made out of a stack of nylon slices.
      Comparisons were also made between the film data and dose calculations made on
      XiO and Monaco treatment planning systems. The collapsed cone algorithm was
      chosen for the XiO and the Monte Carlo algorithm used on Monaco is XVMC.
      Transmission measurements were taken using a narrow-beam geometry to determine
      the mass attenuation coefficient of nylon = 0.0458 cm2 /g and for a water
      equivalent RW3 phantom, it was 0.0465 cm2 /g. The perturbation effects of the
      prosthesis on dose distributions were investigated by measuring and comparing
      dose maps and profiles. The magnitude of dose perturbations was quantified by
      calculating dose enhancement and reduction factors using field sizes of 3 * 3, 5
      * 5, 10 * 10, and 15 * 15 cm2 . For the studied beams and field sizes, dose
      enhancements between 21 and 30% and dose reductions between 15 and 21% were
      observed at the nylon-prosthesis interface on the proximal and distal sides of
      the prosthesis for film measurements. The dose escalation increases with beam
      energy, and the dose reduction due to attenuation decreases with increasing beam
      energy when compared to unattenuated beam data. A comparison of film and XiO
      depth doses for the studied fields gave relative errors between 1.1 and 23.2% at
      the proximal and distal interfaces of the Ti prosthesis. Also, relative errors <
      4.0% were obtained between film and Monaco dose data outside the prosthesis for 6
      and 15 MV lateral opposing fields.

PMID- 28741893
TI  - When epigenetics meets bioengineering-A material characteristics and surface
      topography perspective.
AB  - The field of tissue engineering and regenerative medicine (TE/RM) involves
      regeneration of tissues and organs using implantable biomaterials. The term
      epigenetics refers to changes in gene expression that are not encoded in the DNA
      sequence, leading to remodeling of the chromatin and activation or inactivation
      of gene expression. Recently, studies have demonstrated that these modifications
      are influenced not only by biological cues but also by mechanical and
      topographical signals. This review highlights the current knowledge on emerging
      approaches in TE/RM with a focus on the effect of materials and topography on the
      epigenetic expression pattern in cells with potential impacts on modulating
      regenerative biology. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
      Appl Biomater, 106B: 2065-2071, 2018.

PMID- 28741894
TI  - Randomized Controlled Trial on the Influence of Intraoperative Remifentanil
      versus Fentanyl on Acute and Chronic Pain after Cardiac Surgery.
AB  - BACKGROUND: Remifentanil has been associated with increased acute and potentially
      chronic postoperative pain. The objective of this prospective randomized
      controlled trial was to investigate the influence of intraoperative remifentanil
      on acute and chronic postoperative pain after cardiac surgery. METHODS: Patients
      (N = 126) receiving standardized anesthesia with propofol and intermittent
      intravenous fentanyl at predetermined times for cardiac surgery were randomized
      to intraoperatively receive either a continuous remifentanil infusion or
      additional intermittent intraoperative fentanyl as needed. The primary endpoint
      was chronic thoracic pain at 12 months after surgery. Secondary endpoints were
      pain at 3 and 6 months after surgery and analgesic requirements and pain levels
      in the first 72 hours. RESULTS: There was no significant difference in incidence
      of chronic thoracic pain between the remifentanil and fentanyl groups,
      respectively (20% vs. 18%; P = 0.817). At 3 months, however, significantly more
      patients in the remifentanil group reported chronic thoracic pain (51% vs. 33%; P
      = 0.047). This effect was more pronounced in younger patients and in patients
      receiving a higher dose of remifentanil (both P < 0.05). The first 24 and 48
      hours postoperatively, morphine consumption in the remifentanil group was
      significantly higher than in the fentanyl group (34.3 mg [interquartile range
      (IQR) 25.3 to 48.2] vs. 30.2 mg [IQR 19.2 to 38.1], P = 0.028; and 46.8 mg [IQR
      33.8 to 59.2] vs. 39.0 mg [IQR 6.2 to 51.4], P = 0.047, respectively).
      CONCLUSIONS: Intraoperative use of remifentanil during cardiac surgery does not
      impact chronic postoperative pain 1 year after surgery. Nevertheless,
      remifentanil increases analgesic requirements and thoracic pain until 3 months
      after surgery, and its use is therefore less favorable during cardiac surgery.

PMID- 28741895
TI  - Synthesis of a Doubly Boron-Doped Perylene through NHC-Borenium Hydroboration/C-H
      Borylation/Dehydrogenation.
AB  - Reaction of an N-heterocyclic carbene (NHC)-borenium ion with 9,10
      distyrylanthracene forms four B-C bonds through two selective, tandem
      hydroboration-electrophilic C-H borylations to yield an isolable,
      crystallographically characterizable polycyclic diborenium ion as its [NTf2 ]-
      salt (1). Dehydrogenation of 1 with TEMPO radical followed by acidic workup
      yields a 3,9-diboraperylene as its corresponding borinic acid (2). This sequence
      can be performed in one pot to allow the facile, metal-free conversion of an
      alkene into a small molecule containing a boron-doped graphene substructure.
      Doubly boron-doped perylene 2 exhibits visible range absorbance and fluorescence
      in chloroform solution (Phi=0.63) and undergoes two reversible one-electron
      reductions at moderate potentials of -1.30 and -1.64 eV vs. ferrocenium/ferrocene
      in DMSO. Despite sterically accessible boron centers and facile electrochemical
      reductions, compound 2 is air-, moisture-, and silica gel-stable.

PMID- 28741896
TI  - Therapeutic analysis of Intrabeam-based intraoperative radiation therapy in the
      treatment of unicentric breast cancer lesions utilizing a spherical target volume
      model.
AB  - It is postulated that the outcomes in treating breast cancer with intraoperative
      radiotherapy (IORT) would be affected by the residual cancer cell distribution
      within the tumor bed. The three-dimensional (3D) radiation doses of IntrabeamTM
      (IB) IORT with a 4-cm spherical applicator at the energy of 50 and 40 kV were
      calculated. The modified linear quadratic model (MLQ) was used to estimate the
      radiobiological responses of the cancer cells and interspersed normal tissues
      with various radiosensitivities. By comparing the average survival fraction of
      normal tissues in IB-IORT and uniform dose treatment for the same level of cancer
      cell killing, the therapeutic ratios (TRs) were derived. The equivalent uniform
      dose (EUD) was found to increase with the prescription dose and decrease with the
      cancer cell infiltrating distance. For 50 kV beam at the 20 Gy prescription dose,
      the EUDs are 18.03, 16.49 and 13.56, 11. 29, and 9.28 Gy respectively, for 1.5,
      3.0, 6.0, 9, and 15.0 mm of the cancer cell infiltrating distance into
      surrounding tissue. The dose rate of 50 kV is at least 1.87* higher than that of
      40 kV beam. The EUDs of 50 kV beam are up to 15% higher than that of the 40 kV
      beam. The TR increases with the prescription dose, but decreases with the
      distance of cancer cell infiltration distance. Average TRs of 50 kV beam are up
      to 30% larger than that of 40 kV beam. In conclusion, IB-IORT can provide a
      possible therapeutic advantage on sparing more normal tissue compared with the
      External Beam IORT (EB-IORT) for shallowly populated unicentric breast lesion.
      Our data suggest that IB-IORT dose size should be adjusted based on the
      individual patient's cancer cell infiltrating distance for delivering an
      effective dose, one dose-fits-all regimen may have undertreated some patients
      with large cancer infiltrating distance.

PMID- 28741897
TI  - Recent advances in Pediatric Rheumatology: January to March 2017.

PMID- 28741898
TI  - Development of a New Structural Class of Broadly Acting HCV Non-Nucleoside
      Inhibitors Leading to the Discovery of MK-8876.
AB  - Studies directed at developing a broadly acting non-nucleoside inhibitor of HCV
      NS5B led to the discovery of a novel structural class of 5-aryl benzofurans that
      simultaneously interact with both the palm I and palm II binding regions. An
      initial candidate was potent in vitro against HCV GT1a and GT1b replicons, and
      induced multi-log reductions in HCV viral load when orally dosed to chronic GT1
      infected chimpanzees. However, in vitro potency losses against clinically
      relevant GT1a variants prompted a further effort to develop compounds with
      sustained potency across a broader array of HCV genotypes and mutants.
      Ultimately, a biology and medicinal chemistry collaboration led to the discovery
      of the development candidate MK-8876. MK-8876 demonstrated a pan-genotypic
      potency profile and maintained potency against clinically relevant mutants. It
      demonstrated moderate bioavailability in rats and dogs, but showed low plasma
      clearance characteristics consistent with once-daily dosing. Herein we describe
      the efforts which led to the discovery of MK-8876, which advanced into Phase 1
      monotherapy studies for evaluation and characterization as a component of an all
      oral direct-acting drug regimen for the treatment of chronic HCV infection.

PMID- 28741899
TI  - What the neighbors say.

PMID- 28741900
TI  - The avidity of tumor-specific T cells amplified by a plasmacytoid dendritic cell
      based assay can predict the clinical evolution of melanoma patients.
AB  - The advent of immune checkpoint blockers and targeted therapies has changed the
      outcome of melanoma. However, many patients experience relapses, emphasizing the
      need for predictive and prognostic biomarkers. We developed a strategy based on
      plasmacytoid dendritic cells (pDCs) loaded with melanoma tumor antigens that
      allows eliciting highly efficient antitumor T-cell responses. We used it to
      investigate antitumor T-cell functionality in peripheral blood mononuclear cells
      and tumor-infiltrating lymphocytes from melanoma patients. The pDCs elicited
      tumor-specific T cells in different proportions and displaying diverse functional
      features, dependent upon the stage of the disease, but independent of the
      histological parameters at diagnosis. Strikingly, the avidity of the MelA
      specific T cells triggered by the pDCs was found to predict patient relapse time
      and overall survival. Our findings highlighted unexplored aspects of antitumor T
      cell responsiveness in melanoma, and revealed for the first time the structural
      avidity of tumor-specific T cells as a crucial feature for predicting clinical
      evolution.

PMID- 28741901
TI  - Trends in HCV treatment uptake, efficacy and impact on liver fibrosis in the
      Swiss HIV Cohort Study.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) therapies with interferon-free second
      generation direct-acting antivirals (DAAs) are highly effective and well
      tolerated. They have the potential to increase treatment eligibility and efficacy
      in HIV-infected patients. We assessed the impact of DAAs on treatment uptake and
      efficacy, as well as its impact on the burden of liver disease in the Swiss HIV
      Cohort Study (SHCS). METHODS: We describe clinical and virological
      characteristics of patients treated with second-generation DAAs. We compared
      treatment incidence, sustained virological response (SVR)12 and liver fibrosis
      stages between three time periods: period 1, 01/2009-08/2011 (prior to the
      availability of DAAs); period 2, 09/2011-03/2014 (first generation DAAs); period
      3, 04/2014-12/2015 (second generation DAAs). RESULTS: At the beginning of the
      third period, 876 SHCS participants had a chronic HCV infection of whom 180 (20%)
      started treatment with a second-generation DAA. Three-quarters of them had
      advanced liver fibrosis (Metavir >= F3) of whom 80% were cirrhotics. SVR12 was
      achieved in 173/180 (96%) patients, three patients died and four experienced a
      virological failure. Over the three time periods, treatment uptake (4.5/100 py,
      5.7/100 py, 22.4/100 py) and efficacy (54%, 70%, 96% SVR12) continuously
      increased. The proportion of cirrhotic patients with replicating HCV infection in
      the SHCS declined from 25% at the beginning to 12% at the end of the last period.
      CONCLUSIONS: After the introduction of second-generation DAAs, we observed an
      increase in treatment uptake and efficacy which resulted in a significant
      reduction in the number of cirrhotic patients with a replicating HCV infection in
      the SHCS.

PMID- 28741902
TI  - Corneal confocal sub-basal nerve plexus evaluation: a review.
AB  - The aim of this study was to review the most recent data about corneal sub-basal
      nerve plexus (SNP) evaluated with the use of corneal confocal microscopy (CCM).
      For this purpose, an electronic search was conducted based on PubMed and Google
      Scholar and Web of Science databases from 2008 up to the end of 2016. Ninety
      eight articles in English were cited, as well as abstracts in other languages,
      concerning the morphology and function of corneal SNP in various diseases.
      Changes in corneal SNP as a result of local treatment were also introduced.
      Figures with scans from confocal microscopy from our Department were included.
      The main conclusion of this review was that both corneal SNP diminishment and
      high tortuosity as well as low sensitivity are in principle related to the
      presence or level of pathology. In addition, increased nerve tortuosity may
      represent a morphological determinant of nerve regeneration. However, the
      presented literature shows that SNP changes are not characteristic for one
      unified corneal pathology; rather, they reflect the non-specific pathological
      process present in many diseases. Future studies should use automatized biometric
      software and also examine the effects of new treatments on SNP.

PMID- 28741903
TI  - The acceptability and validity of self-collected nasal swabs for detection of
      influenza virus infection among older adults in Thailand.
AB  - BACKGROUND: Self-collection of nasal swabs could improve the timeliness of
      influenza virus detection in older adults. OBJECTIVES: Measure the acceptability,
      adequacy, timeliness, and validity of self-collected nasal swabs among adults >65
      years in Thailand. METHODS: Our evaluation consisted of two parts: a one-month
      study among randomly selected, community-dwelling older adults to simulate
      community-based surveillance for acute respiratory infections (ARI); and a clinic
      study of older adults with ARI to evaluate the sensitivity and specificity of
      self-collected nasal swabs for influenza virus infection compared with healthcare
      worker (HCW)-collected nasal and nasopharyngeal swabs. RESULTS: In the community
      study, 24% of participants experienced an ARI during the observation period. All
      (100%) participants with an ARI self-collected nasal swabs within 72 hours of
      symptom onset of which 92% were considered adequate samples. In the clinic study,
      45% of patients with ARI presented within 72 hours of symptom onset. The
      sensitivity of self-collected nasal swabs for detection of influenza virus
      infection was 78% (95% CI 40-97) compared to nasopharyngeal and 88% (95% CI 47
      100) compared to nasal swabs collected by HCWs. Specificity was 100% (95% CI 97
      100) compared to both methods. Self-collection of nasal swabs was found
      acceptable by 99% of participants in both studies. CONCLUSIONS: Self-collection
      of nasal swabs was acceptable to older adults in Thailand who were able to take
      adequate samples. Self-collection of nasal swabs may improve the timeliness of
      sample collection but lower sensitivity will need to be considered.

PMID- 28741904
TI  - Prevention of childhood obesity and food policies in Latin America: from research
      to practice.
AB  - BACKGROUND: Addressing childhood obesity in Latin America requires a package of
      multisectoral, evidence-based policies that enable environments conducive to
      healthy lifestyles. OBJECTIVE: Identify and examine key elements to translating
      research into effective obesity policies in Latin America. METHODS: We examined
      obesity prevention policies through case studies developed with an expert in the
      specific policy. Policies were selected based on their level of implementation,
      visibility and potential impact to reduce childhood obesity. They include: (i)
      excise taxes on sugar sweetened beverages and energy-dense foods; (ii) front-of
      package food label legislation; (iii) trans fatty acids removal from processed
      foods; and (iv) Ciclovias recreativas or 'open streets'. Case studies were coded
      to identify components that explained successful implementation and
      sustainability using the Complex Adaptive Health Systems framework. RESULTS: The
      analysis identified key elements for effective and sustainable policy, including
      evidence justifying policy; evidence-based advocacy by civil society; political
      will; and legislation and skillful negotiations across government, academia, the
      private sector and civil society. Scientific evidence and evaluation played an
      important role in achieving tipping points for policies' launch and sustain
      effective implementation. CONCLUSIONS: Well-coordinated, intersectoral
      partnerships are needed to successfully implement evidence-based anti-obesity
      policies. Prospective policy research may be useful for advancing knowledge
      translation.

PMID- 28741905
TI  - Preventing childhood obesity in Latin America: an agenda for regional research
      and strategic partnerships.
AB  - The increasing prevalence of childhood obesity in Latin America poses a major
      public health challenge to the region. In response, many countries are
      implementing obesity prevention programmes aimed at modifying known risk factors.
      However, the limited scientific evidence inhibits the development and
      implementation of novel, effective interventions across the region. To address
      these gaps, the NIH Fogarty International Center convened a workshop of
      researchers, policymakers, programme implementers and public health advocates who
      are actively engaged in the region to prevent childhood obesity. Major aims of
      the meeting were to define the current status of childhood obesity, identify the
      scientific gaps in our understanding of the epidemic, point out the barriers and
      opportunities for research and outline a plan for capacity building in the region
      in the area of childhood obesity. This series of articles reflects the key
      outcome of the meeting and offers an analysis of the knowledge translation needed
      for evidence-based policy initiatives, a review of the research agenda and an
      evaluation of research capacity in the region. The goal of the papers is to
      inform the development of multidisciplinary and multisector research
      collaborations, which are essential to the implementation of successful childhood
      obesity prevention strategies in the region.

PMID- 28741906
TI  - A research agenda to guide progress on childhood obesity prevention in Latin
      America.
AB  - Childhood obesity rates in Latin America are among the highest in the world. This
      paper examines and evaluates the many efforts underway in the region to reduce
      and prevent further increases in obesity, identifies and discusses unique
      research challenges and opportunities in Latin America, and proposes a research
      agenda in Latin America for the prevention of childhood obesity and concomitant
      non-communicable diseases. Identified research gaps include biological challenges
      to healthy growth across the life cycle, diet and physical activity dynamics,
      community interventions promoting healthy child growth, and rigorous evaluation
      of national food and activity programs and regulatory actions. Addressing these
      research gaps is critical to advance the evidence-based policy and practice in
      childhood obesity tailored to the Latin American context that will be effective
      in addressing obesity.

PMID- 28741908
TI  - Research capacity for childhood obesity prevention in Latin America: an area for
      growth.
AB  - BACKGROUND: The rise of childhood obesity in Latin America calls for research
      capacity to understand, monitor and implement strategies, policies and programmes
      to address it. OBJECTIVE: The objective of the study was to assess current
      research capacity in Latin America related to childhood obesity, nutrition and
      physical activity. METHODS: We conducted a search of peer-reviewed articles on
      childhood obesity in Latin America with at least one Latin American author from
      2010 to May 2015. We coded 484 published articles for author affiliation, study
      subjects' nationality, research topic and study design and extracted a series of
      networks per research topic, study design and collaborating country for each of
      the countries. RESULTS: Obesity is the most frequently explored topic. Nutrition
      and obesity are somewhat better developed compared with physical activity and
      sedentary behaviour. There are numerous observational and cross-sectional
      studies, indicating either a lack of capacity required for more complex research
      or the extent of the problem and associated factors is still unknown. The low
      number of intervention studies and the near absence of policy articles suggest a
      void in research capacity. CONCLUSION: For childhood obesity, there is a clear
      need to build research capacity that documents the current state of the problem
      and design evidence-based prevention and intervention efforts.

PMID- 28741907
TI  - Nutrition status of children in Latin America.
AB  - The prevalence of overweight and obesity is rapidly increasing among Latin
      American children, posing challenges for current healthcare systems and
      increasing the risk for a wide range of diseases. To understand the factors
      contributing to childhood obesity in Latin America, this paper reviews the
      current nutrition status and physical activity situation, the disparities between
      and within countries and the potential challenges for ensuring adequate nutrition
      and physical activity. Across the region, children face a dual burden of
      undernutrition and excess weight. While efforts to address undernutrition have
      made marked improvements, childhood obesity is on the rise as a result of diets
      that favour energy-dense, nutrient-poor foods and the adoption of a sedentary
      lifestyle. Over the last decade, changes in socioeconomic conditions,
      urbanization, retail foods and public transportation have all contributed to
      childhood obesity in the region. Additional research and research capacity are
      needed to address this growing epidemic, particularly with respect to designing,
      implementing and evaluating the impact of evidence-based obesity prevention
      interventions.

PMID- 28741909
TI  - A prospective evaluation of the established criteria for heart failure with
      preserved ejection fraction using the Alberta HEART cohort.
AB  - AIMS: Heart failure with a preserved ejection fraction (HF-PEF) remains a
      difficult clinical diagnosis. The aim of this study was to test the utility of
      established criteria to classify patients with HF-PEF. We prospectively enrolled
      patients into one of five groups across a spectrum of cardiac disease and applied
      three different criteria for HF-PEF and calculated diagnostic metrics. METHODS
      AND RESULTS: A total of 565 patients were included in the analysis, including 170
      patients with an adjudicated diagnosis of HF-PEF, 152 patients with heart failure
      with reduced ejection fraction, 152 patients at risk for heart failure, and 91
      age-matched healthy controls. For the diagnosis of HF-PEF, the positive
      likelihood ratios were 6.1, 6.9, and 4.8 for the Zile, European Society of
      Cardiology (ESC) 2007, and ESC 2016 criteria, respectively. The negative
      likelihood ratios were 0.58, 0.60, and 0.42 for the Zile, ESC 2007, and ESC 2016
      criteria, respectively. All three criteria lacked sensitivity to detect HF-PEF
      (46.5%, 44.1%, and 51.8%, respectively) but were highly specific (92.4%, 93.9%,
      and 89%, respectively). We further evaluated the criteria to distinguish HF-PEF
      from other diagnoses after excluding heart failure with reduced ejection
      fraction; the results were similar. CONCLUSIONS: In this community based cohort,
      the likelihood ratios of the existing criteria for HF-PEF were not at the level
      necessary to be considered diagnostic. Improved criteria for the diagnosis of
      patients with HF-PEF are needed.

PMID- 28741910
TI  - The Study of Suff erring.

PMID- 28741912
TI  - The Authors Respond.

PMID- 28741911
TI  - More on Laser Treatment of Periodontal Disease.

PMID- 28741913
TI  - Informed Consent.

PMID- 28741914
TI  - Study Aims to Reduce Pain for Oral Cancer Patients.

PMID- 28741915
TI  - Making a Titanium Surface Biologically Active.

PMID- 28741916
TI  - Study Links Vaping to Tobacco Use in Teens.

PMID- 28741917
TI  - Drinking Sugary Sports Drinks a Social Activity for Teens.

PMID- 28741918
TI  - Extrafamilial, Interfamilial Transmission of S. mutans.

PMID- 28741919
TI  - ADA President Calls on Dentists to Help Curb Opioid Abuse.

PMID- 28741920
TI  - New Reliever of Jaw Pain Discovered.

PMID- 28741921
TI  - Bioinspired Composite Matrix Containing Hydroxyapatite-Silica Core-Shell Nanorods
      for Bone Tissue Engineering.
AB  - Development of multifunctional bioinspired scaffolds that can stimulate
      vascularization and regeneration is necessary for the application in bone tissue
      engineering. Herein, we report a composite matrix containing hydroxyapatite (HA)
      silica core-shell nanorods with good biocompatibility, osteogenic
      differentiation, vascularization, and bone regeneration potential. The
      biomaterial consists of a crystalline, rod-shaped nanoHA core with uniform
      amorphous silica sheath (Si-nHA) that retains the characteristic phases of the
      individual components, confirmed by high-resolution transmission electron
      microscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, and Fourier
      transform infrared spectroscopy. The nanorods were blended with gelatinous matrix
      to develop as a porous, composite scaffold. The viability and functionality of
      osteogenically induced mesenchymal stem cells as well as endothelial cells have
      been significantly improved through the incorporation of Si-nHA within the
      matrix. Studies in the chicken chorioallantoic membrane and rat models
      demonstrated that the silica-containing scaffolds not only exhibit good
      biocompatibility, but also enhance vascularization in comparison to the matrix
      devoid of silica. Finally, when tested in a critical-sized femoral segmental
      defect in rats, the nanocomposite scaffolds enhanced new bone formation in par
      with the biomaterial degradation. In conclusion, the newly developed composite
      biomimetic scaffold may perform as a promising candidate for bone tissue
      engineering applications.

PMID- 28741922
TI  - An Unusual Mechanism for Negative Differential Resistance in Ferroelectric
      Nanocapacitors: Polarization Switching-Induced Charge Injection Followed by
      Charge Trapping.
AB  - Negative differential resistance (NDR) has been extensively investigated for its
      wide device applications. However, a major barrier ahead is the low reliability.
      To address the reliability issues, we consider ferroelectrics and propose an
      alternative mechanism for realizing the NDR with deterministic current peak
      positions, in which the NDR results from the polarization switching-induced
      charge injection and subsequent charge trapping at the metal/ferroelectric
      interface. In this work, ferroelectric Au/BiFe0.6Ga0.4O3 (BFGO)/Ca0.96Ce0.04MnO3
      (CCMO) nanocapacitors are prepared, and their ferroelectricity and NDR behaviors
      are studied concurrently. It is observed that the NDR current peaks are located
      at the vicinity of coercive voltages (Vc) of the ferroelectric nanocapacitors,
      thus evidencing the proposed mechanism. In addition, the NDR effect is
      reproducible and robust with good endurance and long retention time. This study
      therefore demonstrates a ferroelectric-based NDR device, which may facilitate the
      development of highly reliable NDR devices.

PMID- 28741923
TI  - Co-Delivery of Trichosanthin and Albendazole by Nano-Self-Assembly for Overcoming
      Tumor Multidrug-Resistance and Metastasis.
AB  - Multidrug resistance (MDR) and metastasis are the major obstacles in cancer
      chemotherapy. Nanotechnology-based combination therapy is a useful strategy.
      Recently, the combination of biologics and small drugs has attracted much
      attention in cancer therapy. Yet, the treatment outcomes are often compromised by
      the different pharmacokinetic profiles of the co-administered drugs thus leading
      to inconsistent drug uptake and suboptimal drug combination at the tumor sites.
      Nanotechnology-based co-delivery offers a promising method to address this
      problem, which is well demonstrated in the use of small drug combinations.
      However, co-delivery of the drugs bearing different physicochemical properties
      (e.g., proteins and small drugs) remains a formidable challenge. Herein, we
      developed a self-assembled nanosystem for co-delivery of trichosanthin (TCS)
      protein and albendazole (ABZ) as a combination therapy for overcoming MDR and
      metastasis. TCS is a ribosome-inactivating protein with high antitumor activity.
      However, the druggability of TCS is poor due to its short half-life, lack of
      tumor-specific action, and low cell uptake. ABZ is a clinically used
      antihelmintic drug, which can also inhibit tubulin polymerization and thus serve
      as a potential antitumor drug. In our work, ABZ was encapsulated in the albumin
      coated silver nanoparticles (termed ABZ@BSA/Ag NP). The thus-formed NPs were
      negatively charged and could tightly bind with the cationic TCS that was modified
      with a cell-penetrating peptide (CPP) low-molecular-weight protamine (termed
      rTL). Via the stable charge interaction, the nanosystem (rTL/ABZ@BSA/Ag NP) was
      self-assembled, and featured by the TCS corona. The co-delivery system
      efficiently inhibited the proliferation of the drug-resistant tumor cells (A549/T
      and HCT8/ADR) by impairing the cytoskeleton, arresting the cell cycle, and
      enhancing apoptosis. In addition, the migration and invasion of tumor cells were
      inhibited presumably due to the impeded cytoskeleton functions. The anti-MDR
      effect was further confirmed by the in vivo studies with the subcutaneous A549/T
      tumor mouse model. More importantly, the co-delivery system was demonstrated to
      be able to inhibit metastasis. The co-delivery system of TCS/ABZ provided a
      potential strategy for both overcoming drug resistance and inhibiting tumor
      metastasis.

PMID- 28741924
TI  - Ultrasound-Responsive Polymeric Micelles for Sonoporation-Assisted Site-Specific
      Therapeutic Action.
AB  - Targeting drug delivery remains a challenge in various disease treatment
      including cancer. The local drug deposit could be greatly enhanced by some
      external stimuli-responsive systems. Here we develop pluronic P123/F127 polymeric
      micelles (M) encapsulating curcumin (Cur) that are permeabilized directly by
      focused ultrasound, in which ultrasound triggers drug release. Tumor preferential
      accumulation and site-specific sonochemotherapy were then evaluated. Cur-loaded
      P123/F127 mixed micelles (Cur-M) exhibited longer circulating time and increased
      cellular uptake compared to free Cur. With the assistance of focused ultrasound
      treatment, Cur-M showed tumor-targeting deposition in a time-dependent manner
      following systemic administration. This was due to enhanced permeabilization of
      tumor regions and increased penetration of Cur-M in irradiated tumor cells by
      ultrasound sonoporation. Furthermore, Cur-M self-assembly could be regulated by
      ultrasound irradiation. In vitro Cur release from mixed micelles was greatly
      dependent on ultrasound intensity but not on duration, suggesting the
      cavitational threshold was necessary to initiate subsequent sonochemotherapy. In
      vivo site-specific drug release was demonstrated in dual-tumor models, which
      showed spatial-temporal release of entrapped drugs following intratumoral
      injection. The sonoporation-assisted site-specific chemotherapy significantly
      inhibited tumor growth and the decrease in tumor weight was approximately 6.5
      fold more than without exposure to ultrasound irradiation. In conclusion, the
      established ultrasound-guided nanomedicine targeting deposit and local release
      may represent a new strategy to improve chemotherapy efficiency.

PMID- 28741925
TI  - An Efficient One-Pot Synthesis of Densely Functionalized Fused-Quinolines via
      Sequential Ugi4CC and Acid-Mediated Povarov-Type Reaction.
AB  - A divergent synthesis of fused-quinolines has been explored by performing Ugi
      four-component condensation and sulfuric acid promoted deprotection/Povarov-type
      reaction in one-pot. The process involves Ugi condensation of propiolic acids,
      aldehydes/ketones, aminoaldehyde acetals and isocyanides followed by sulfuric
      acid promoted deprotection and Povarov-type reaction with anilines in ethanol.
      This method enables straightforward access to the structurally diverse 2,3
      dihydro-1H-pyrrolo[3,4-b]quinolin-1-ones (DHPQ), 3,4
      dihydrobenzo[b][1,6]naphthyridin-1(2H)-ones (DHBN), and 2,3,4,5-tetrahydro-1H
      azepino[4,3-b]quinolin-1-ones (THAQ), starting from readily available starting
      materials.

PMID- 28741926
TI  - Redesigned Spider Peptide with Improved Antimicrobial and Anticancer Properties.
AB  - Gomesin, a disulfide-rich antimicrobial peptide produced by the Brazilian spider
      Acanthoscurria gomesiana, has been shown to be potent against Gram-negative
      bacteria and to possess selective anticancer properties against melanoma cells.
      In a recent study, a backbone cyclized analogue of gomesin was shown to be as
      active but more stable than its native form. In the current study, we were
      interested in improving the antimicrobial properties of the cyclic gomesin,
      understanding its selectivity toward melanoma cells and elucidating its
      antimicrobial and anticancer mode of action. Rationally designed analogues of
      cyclic gomesin were examined for their antimicrobial potency, selectivity toward
      cancer cells, membrane-binding affinity, and ability to disrupt cell and model
      membranes. We improved the activity of cyclic gomesin by ~10-fold against tested
      Gram-negative and Gram-positive bacteria without increasing toxicity to human red
      blood cells. In addition, we showed that gomesin and its analogues are more toxic
      toward melanoma and leukemia cells than toward red blood cells and act by
      selectively targeting and disrupting cancer cell membranes. Preference toward
      some cancer types is likely dependent on their different cell membrane
      properties. Our findings highlight the potential of peptides as antimicrobial and
      anticancer leads and the importance of selectively targeting cancer cell
      membranes for drug development.

PMID- 28741927
TI  - Rapid Antibiotic Susceptibility Testing of Uropathogenic E. coli by Tracking
      Submicron Scale Motion of Single Bacterial Cells.
AB  - To combat antibiotic resistance, a rapid antibiotic susceptibility testing (AST)
      technology that can identify resistant infections at disease onset is required.
      Current clinical AST technologies take 1-3 days, which is often too slow for
      accurate treatment. Here we demonstrate a rapid AST method by tracking sub-MUm
      scale bacterial motion with an optical imaging and tracking technique. We apply
      the method to clinically relevant bacterial pathogens, Escherichia coli O157: H7
      and uropathogenic E. coli (UPEC) loosely tethered to a glass surface. By
      analyzing dose-dependent sub-MUm motion changes in a population of bacterial
      cells, we obtain the minimum bactericidal concentration within 2 h using human
      urine samples spiked with UPEC. We validate the AST method using the standard
      culture-based AST methods. In addition to population studies, the method allows
      single cell analysis, which can identify subpopulations of resistance strains
      within a sample.

PMID- 28741928
TI  - Selection of Effective HTRA3 Activators Using Combinatorial Chemistry.
AB  - Herein, we report selection, synthesis, and enzymatic evaluation of a
      peptidomimetic library able to increase proteolytic activity of HtrA3 (high
      temperature requirement A) protease. Iterative deconvolution in solution of
      synthesized modified pentapeptides yielded two potent HtrA3 activators acting in
      the micromolar range (HCOO-CH2O-C6H4-OCH2-CO-Tyr-Asn-Phe-His-Asn-OH and HCOO-CH2O
      C6H4-OCH2-CO-Tyr-Asn-Phe-His-Glu-OH). Both compounds increased proteolysis of an
      artificial HtrA3 substrate over 40-fold in a selective manner. On the basis of
      molecular modeling, the selected compounds bind strongly to the PDZ domain.

PMID- 28741929
TI  - Putidaredoxin Binds to the Same Site on Cytochrome P450cam in the Open and Closed
      Conformation.
AB  - Cytochrome P450 CYP101A1 (P450cam) hydroxylates camphor by receiving two distinct
      electrons from its unique reductase, putidaredoxin (Pdx). Upon binding ferric
      P450cam, Pdx is now known to trigger a conformational change in the enzyme. This
      Pdx-induced conversion may provide the trigger to coordinate enzyme turnover and
      protect the enzyme from oxidative damage, so the interactions responsible for
      this conversion are of significant interest at present. This proposed role for
      Pdx requires that its interactions with P450cam be different for the open and
      closed conformations. In this study, we show that the binding thermodynamics of
      Pdx does indeed differ in the predicted way when the conformation of P450cam is
      held in different states. However, double electron-electron resonance
      measurements of intermolecular distances in the Pdx/P450cam complex show that the
      geometry of the complex is nearly identical for the open and closed states of
      P450cam. These studies show that Pdx appears to make a single distinct
      interaction with its binding site on the enzyme and triggers the conformational
      change through very subtle structural interactions.

PMID- 28741930
TI  - N-Terminal Acetylation Preserves alpha-Synuclein from Oligomerization by Blocking
      Intermolecular Hydrogen Bonds.
AB  - The abnormal aggregation of alpha-synuclein (alpha-Syn) is closely associated
      with Parkinson's disease. Different post-translational modifications of alpha-Syn
      have been identified and contribute distinctly in alpha-Syn aggregation and
      cytotoxicity. Recently, alpha-Syn was reported to be N-terminally acetylated in
      cells, yet the functional implication of this modification, especially in alpha
      Syn oligomerization, remains unclear. By using a solid-state nanopore system, we
      found that N-terminal acetylation can significantly decrease alpha-Syn
      oligomerization. Replica-exchange molecular dynamics simulations further revealed
      that addition of an acetyl group at the N-terminus disrupts intermolecular
      hydrogen bonds, which slows down the initial alpha-Syn oligomerization. Our
      finding highlights the essential role of N-terminal acetylation of alpha-Syn in
      preserving its native conformation against pathological aggregation.

PMID- 28741931
TI  - Chromium(II) Metal-Organic Polyhedra as Highly Porous Materials.
AB  - Herein we report for the first time the synthesis of Cr(II)-based metal-organic
      polyhedra (MOPs) and the characterization of their porosities. Unlike the
      isostructural Cu(II)- or Mo(II)-based MOPs, Cr(II)-based MOPs show unusually high
      gas uptakes and surface areas. The combination of comparatively robust dichromium
      paddlewheel units (Cr2 units), cage symmetries, and packing motifs enable these
      materials to achieve Brunauer-Emmett-Teller surface areas of up to 1000 m2/g.
      Reducing the aggregation of the Cr(II)-based MOPs upon activation makes their
      pores more accessible than their Cu(II) or Mo(II) counterparts. Further
      comparisons of surface areas on a molar (m2/mol cage) rather than gravimetric
      (m2/g) basis is proposed as a rational method of comparing members of a family of
      related molecular materials.

PMID- 28741932
TI  - Tailor-Made Luminescent Polymers through Unusual Metallophilic Interaction Arrays
      Au...Au...Ag...Ag.
AB  - A novel and efficient strategy for the synthesis of luminescent polymers bearing
      metallophilic interactions with unprecedented charge sequences has been designed.
      For this end suitable basic gold units such as [AuR2]-, bearing perhalophenyl
      derivatives, and dinuclear acid silver terpyridine species,
      [Ag2(terpy)2](CF3SO3)2, have been chosen. Their combination originates the
      polymeric derivatives [{AuR2}2Ag2(terpy)2]n (R = C6F5, C6Cl2F3) or
      [{Au(C6Cl5)2}Ag(terpy)]n. The change of the perhalophenyl group in the gold
      complex modulates the strength in the metallophilic contacts and, consequently,
      the polymer arrays and luminescent properties. The X-ray diffraction studies of
      these derivatives revealed that there are polymers with unusual + + - - + + - -
      charge sequences for the R = C6F5 and C6Cl2F3 species, whereas the more classical
      + - + - disposition was found for the bulkiest C6Cl5 derivative. Their
      luminescent properties also vary depending on the formation of these polymer
      arrays, and time-dependent density functional theory calculations were performed
      to determine the origin of the luminescence.

PMID- 28741933
TI  - Functionalized Cobalt Triarylcorrole Covalently Bonded with Graphene Oxide: A
      Selective Catalyst for the Two- or Four-Electron Reduction of Oxygen.
AB  - A cobalt triphenylcorrole (CorCo) was covalently bonded to graphene oxide (GO),
      and the resulting product, represented as GO-CorCo, was characterized by UV-vis,
      FT-IR, and micro-Raman spectroscopy as well as by HRTEM, TGA, XRD, XPS, and AFM.
      The electrocatalytic activity of GO-CorCo toward the oxygen reduction reaction
      (ORR) was then examined in air-saturated 0.1 M KOH and 0.5 M H2SO4 solutions by
      cyclic voltammetry and linear sweep voltammetry using a rotating disk electrode
      and/or a rotating ring-disk electrode. An overall 4-electron reduction of O2 is
      obtained in alkaline media while under acidic conditions a 2-electron process is
      seen. The ORR results thus indicate that covalently bonded GO-CoCor can be used
      as a selective catalyst for either the 2- or 4-electron reduction of oxygen, the
      prevailing reaction depending upon the acidity of the solution.

PMID- 28741934
TI  - Mixed-Spin Diamond Chain Cu2FePO4F4(H2O)4 with a Noncollinear Spin Order and
      Possible Successive Phase Transitions.
AB  - A diamond spin chain system, one of the one-dimensional frustrated lattices, is
      known to exhibit novel properties, but experimental studies have been exclusively
      confined to materials with a single spin component. Here, we report on the
      synthesis, structure, and magnetic properties of a new diamond chain compound
      Cu2FePO4F4(H2O)4 1 composed of mixed-spins of Cu2+ (S = 1/2 * 2) and Fe3+ (S =
      5/2). Compound 1 crystallizes in the space group C2/c of the monoclinic crystal
      system with a = 7.7546(4) A, b = 12.1290(6) A, c = 9.9209(6) A, beta = 105.29(1)
      degrees , and Z = 4. DC magnetization, Mossbauer spectroscopy, and heat capacity
      measurements revealed an antiferromagnetic order at 11.3 K with a small
      ferromagnetic component. It is suggested that ferrimagnetic diamond chains are
      arranged in an antiferromagnetic fashion (i.e., [...Fe(?)-2Cu(??)-Fe(?)...] and
      [...Fe(?)-2Cu(??)-Fe(?)...]) within the ab plane to cancel net magnetization, and
      the spin orientation of the diamond chains changes alternately along the c axis
      due to the magnetic anisotropy, leading to a noncollinear spin order.
      Furthermore, another anomaly is observed in the heat capacity at around 3 K,
      suggesting a successive magnetic transition or crossover due to competing
      magnetic interactions.

PMID- 28741935
TI  - Super-Photostable Phosphole-Based Dye for Multiple-Acquisition Stimulated
      Emission Depletion Imaging.
AB  - As stimulated emission depletion (STED) microscopy can provide structural details
      of cells with an optical resolution beyond the diffraction limit, it has become
      an indispensable tool in cell biology. However, the intense STED laser beam
      usually causes rapid photobleaching of the employed fluorescent dyes, which
      significantly limits the utility of STED microscopy from a practical perspective.
      Herein we report a new design of super-photostable dye, PhoxBright 430 (PB430),
      comprising a fully ring-fused pi-conjugated skeleton with an electron-accepting
      phosphole P-oxide unit. We previously developed a super-photostable dye C-Naphox
      by combining the phosphole unit with an electron-donating triphenylamine moiety.
      In PB430, removal of the amino group alters the transition type from
      intramolecular charge transfer character to pi-pi* transition character, which
      gives rise to intense fluorescence insensitive to molecular environment in terms
      of fluorescence colors and intensity, and bright fluorescence even in aqueous
      media. PB430 also furnishes high solubility in water, and is capable of labeling
      proteins with maintaining high fluorescence quantum yields. This dye exhibits
      outstanding resistance to photoirradiation even under the STED conditions and
      allows continuous acquisition of STED images. Indeed, using a PB430-conjugated
      antibody, we succeed in attaining a 3-D reconstruction of super-resolution STED
      images as well as photostability-based multicolor STED imaging of fluorescently
      labeled cytoskeletal structures.

PMID- 28741936
TI  - Influence of Lattice Polarizability on the Ionic Conductivity in the Lithium
      Superionic Argyrodites Li6PS5X (X = Cl, Br, I).
AB  - In the search for novel solid electrolytes for solid-state batteries,
      thiophosphate ionic conductors have been in recent focus owing to their high
      ionic conductivities, which are believed to stem from a softer, more polarizable
      anion framework. Inspired by the oft-cited connection between a soft anion
      lattice and ionic transport, this work aims to provide evidence on how changing
      the polarizability of the anion sublattice in one structure affects ionic
      transport. Here, we systematically alter the anion framework polarizability of
      the superionic argyrodites Li6PS5X by controlling the fractional occupancy of the
      halide anions (X = Cl, Br, I). Ultrasonic speed of sound measurements are used to
      quantify the variation in the lattice stiffness and Debye frequencies. In
      combination with electrochemical impedance spectroscopy and neutron diffraction,
      these results show that the lattice softness has a striking influence on the
      ionic transport: the softer bonds lower the activation barrier and simultaneously
      decrease the prefactor of the moving ion. Due to the contradicting influence of
      these parameters on ionic conductivity, we find that it is necessary to tailor
      the lattice stiffness of materials in order to obtain an optimum ionic
      conductivity.

PMID- 28741937
TI  - Lanthanide Organophosphate Spiro Polymers: Synthesis, Structure, and
      Magnetocaloric Effect in the Gadolinium Polymer.
AB  - Spirocyclic lanthanide organophosphate polymers,
      {[Ln(dipp)(dippH)(CH3OH)(H2O)2](CH3OH)2}n [Ln = La (1), Ce (2), Pr (3), Nd (4),
      Sm (5), Eu (6), Gd (7), Tb (8), Dy (9), Ho (10), Er (11)], have been prepared
      from the reaction of Ln(NO3)3.xH2O with sterically hindered 2,6-diisopropylphenyl
      phosphate (dippH2) using aqueous NaOH as the base. The one-dimensional chainlike
      lanthanide (III) organophosphate coordination polymers have been characterized
      with the aid of analytical and spectroscopic methods. The single crystal
      structure determination of polymers (2-5 and 7-11) reveals that in these
      compounds the hydrophobic organic groups of the phosphate provide a protective
      coating for the inorganic lanthanide phosphate polymeric chain. The encapsulation
      of inorganic lanthanide phosphate core, which has very low solubility product,
      within the organic groups assists in the facile crystallization of the polymers.
      The di- and monoanionic organophosphate ligands dipp2- and dippH- display [2.111]
      and [2.110] binding modes, respectively, in 2-5 and 7. However, they exhibit only
      [2.110] binding mode in the case of 8-11. This results in the formation of two
      different types of polymers. While the lighter rare-earth metal ions in 2-5 and 7
      display eight coordinate biaugmented trigonal prismatic geometry, the heavier
      rare-earth metal ions in 9-11 exhibit a seven coordinate capped trigonal
      prismatic environment. The Tb(III) ion in 8 displays distorted pentagonal
      bipyramidal geometry. Magnetic studies reveal the presence of weak
      antiferromagnetic interactions between the Ln(III) ions through the
      organophosphate ligand. The isotropic Gd(III) polymer 7 exhibits a maximum
      entropy change of 17.83 J kg-1 K-1 for a field change of 7.0 T at 2.5 K, which is
      significant considering the high molecular weight of the organophosphate ligand.
      These polymers represent the first family of any structurally characterized rare
      earth organophosphate polymers derived from monoesters of phosphoric acid.

PMID- 28741938
TI  - New Synthesis of nZVI/C Composites as an Efficient Adsorbent for the Uptake of
      U(VI) from Aqueous Solutions.
AB  - New nanoscale zerovalent iron/carbon (nZVI/C) composites were successfully
      prepared via heating natural hematite and pine sawdust at 800  degrees C under
      nitrogen conditions. Characterization by SEM, XRD, FTIR, and XPS analyses
      indicated that the as-prepared nZVI/C composites contained a large number of
      reactive sites. The lack of influence of the ionic strength revealed inner-sphere
      complexation dominated U(VI) uptake by the nZVI/C composites. Simultaneous
      adsorption and reduction were involved in the uptake process of U(VI) according
      to the results of XPS and XANES analyses. The presence of U-C/U-U shells
      demonstrated that innersphere complexation and surface coprecipitation dominated
      the U(VI) uptake at low and high pH conditions, respectively. The uptake
      behaviors of U(VI) by the nZVI/C composites were fitted well by surface
      complexation modeling with two weak and two strong sites. The maximum uptake
      capacity of U(VI) by the nZVI/C composites was 186.92 mg/g at pH 4.0 and 328 K.
      Additionally, the nZVI/C composites presented good recyclability and
      recoverability for U(VI) uptake in regeneration experiments. These observations
      indicated that the nZVI/C composites can be considered as potential adsorbents to
      remove radionuclides for environmental remediation.

PMID- 28741939
TI  - Influence of Electric Fields on Biofouling of Carbonaceous Electrodes.
AB  - Biofouling commonly occurs on carbonaceous capacitive deionization electrodes in
      the process of treating natural waters. Although previous work reported the
      effect of electric fields on bacterial mortality for a variety of medical and
      engineered applications, the effect of electrode surface properties and the
      magnitude and polarity of applied electric fields on biofilm development has not
      been comprehensively investigated. This paper studies the formation of a
      Pseudomonas aeruginosa biofilm on a Papyex graphite (PA) and a carbon aerogel
      (CA) in the presence and the absence of an electric field. The experiments were
      conducted using a two-electrode flow cell with a voltage window of +/-0.9 V. The
      CA was less susceptible to biofilm formation compared to the PA due to its lower
      surface roughness, lower hydrophobicity, and significant antimicrobial
      properties. For both positive and negative applied potentials, we observed an
      inverse relationship between biofilm formation and the magnitude of the applied
      potential. The effect is particularly strong for the CA electrodes and may be a
      result of cumulative effects between material toxicity and the stress experienced
      by cells at high applied potentials. Under the applied potentials for both
      electrodes, high production of endogenous reactive oxygen species (ROS) was
      indicative of bacterial stress. For both electrodes, the elevated specific ROS
      activity was lowest for the open circuit potential condition, elevated when
      cathodically and anodically polarized, and highest for the +/-0.9 V cases. These
      high applied potentials are believed to affect the redox potential across the
      cell membrane and disrupt redox homeostasis, thereby inhibiting bacterial growth.

PMID- 28741940
TI  - Directed beta C-H Amination of Alcohols via Radical Relay Chaperones.
AB  - A radical-mediated strategy for beta C-H amination of alcohols has been
      developed. This approach employs a radical relay chaperone, which serves as a
      traceless director that facilitates selective C-H functionalization via 1,5
      hydrogen atom transfer (HAT) and enables net incorporation of ammonia at the beta
      carbon of alcohols. The chaperones presented herein enable direct access to
      imidate radicals, allowing their first use for H atom abstraction. A streamlined
      protocol enables rapid conversion of alcohols to their beta-amino analogs (via in
      situ conversion of alcohols to imidates, directed C-H amination, and hydrolysis
      to NH2). Mechanistic experiments indicate HAT is rate-limiting, whereas
      intramolecular amination is product- and stereo-determining.

PMID- 28741941
TI  - Efficient Delivery of Quantum Dots into the Cytosol of Cells Using Cell
      Penetrating Poly(disulfide)s.
AB  - Quantum dots (QDs) are extremely bright, photostable, nanometer particles broadly
      used to investigate single molecule dynamics in vitro. However, the use of QDs in
      vivo to investigate single molecule dynamics is impaired by the absence of an
      efficient way to chemically deliver them into the cytosol of cells. Indeed,
      current methods (using cell-penetrating peptides for instance) provide very low
      yields: QDs stay at the plasma membrane or are trapped in endosomes. Here, we
      introduce a technology based on cell-penetrating poly(disulfide)s that solves
      this problem: we deliver about 70 QDs per cell, and 90% appear to freely diffuse
      in the cytosol. Furthermore, these QDs can be functionalized, carrying GFP or
      anti-GFP nanobodies for instance. Our technology thus paves the way toward single
      molecule imaging in cells and living animals, allowing to probe biophysical
      properties of the cytosol.

PMID- 28741942
TI  - Tuning the Stability of Pd(IV) Intermediates Using a Redox Non-innocent Ligand
      Combined with an Organolanthanide Fragment.
AB  - The unique combination of a divalent organolanthanide fragment, Cp*2Yb, with
      bipyrimidine (bipym) and a palladium bis-alkyl fragment, PdMe2, allows the rapid
      formation and stabilization of a PdIV tris-alkyl moiety after oxidative addition
      with MeI. The crucial role of the organolanthanide fragment is demonstrated by
      the substitution of bipym by the 4,5,9,10-tetraazaphenanthrene ligand, which
      drastically modifies the electronic structure and tunes the stability of the PdIV
      species.

PMID- 28741943
TI  - Reductive Etherification via Anion-Binding Catalysis.
AB  - Reductive condensations of alcohols with aldehydes/ketones to generate ethers are
      catalyzed by a readily accessible thiourea organocatalyst that operates in
      combination with HCl. 1,1,3,3-tetramethyldisiloxane serves as a convenient
      reducing reagent. This strategy is applicable to challenging substrate
      combinations and exhibits functional group tolerance. Competing reductive
      homocoupling of the carbonyl component is suppressed.

PMID- 28741944
TI  - Substrate Recognition of Glycoprotein Folding Sensor UGGT Analyzed by Site
      Specifically 15N-Labeled Glycopeptide and Small Glycopeptide Library Prepared by
      Parallel Native Chemical Ligation.
AB  - UDP-glucose:glycoprotein glucosyltransferase (UGGT) distinguishes glycoproteins
      in non-native conformations from those in native conformations and glucosylates
      from only non-native glycoproteins. To analyze how UGGT recognizes non-native
      glycoproteins, we chemically synthesized site-specifically 15N-labeled
      interleukin 8 (IL-8) C-terminal (34-72) glycopeptides bearing a Man9GlcNAc2 (M9)
      oligosaccharide. Chemical shift perturbation mapping NMR experiments suggested
      that Phe65 of the glycopeptide specifically interacts with UGGT. To analyze this
      interaction, we constructed a glycopeptide library by varying Phe65 with 10 other
      natural amino acids, via parallel native chemical ligation between a glycopeptide
      alpha-thioester and a peptide library consisting of 11 peptides. UGGT assay
      against the glycopeptide library revealed that, although less hydrophobic
      glycopeptides could be used as substrates for UGGT, hydrophobic glycopeptides are
      preferred.

PMID- 28741945
TI  - Copper-Catalyzed Oxidative Coupling of beta-Keto Esters with N-Methylamides for
      the Synthesis of Symmetrical 2,3,5,6-Tetrasubstituted Pyridines.
AB  - A copper-catalyzed oxidative formal [2+2+1+1] cycloaddition for the synthesis of
      symmetrical tetrasubstituted pyridines was first demonstrated. The reaction is
      involved in a domino cross-dehydrogenative coupling (CDC) of beta-keto esters and
      N-methylamides, the C-N bond cleavage, the Michael addition, and a condensation
      and oxidative aromatization process. Multiple C-C and C-N bonds were constructed
      in one pot via the C-H and C-N cleavage of N-methylamides, which were employed as
      the carbon source of pyridines. The preliminary mechanistic studies revealed that
      the C(sp3)-H bond cleavage of N-methylamides was the rate-determining step.

PMID- 28741946
TI  - Investigating Substrate Scope and Enantioselectivity of a Defluorinase by a
      Stereochemical Probe.
AB  - The possibility of a double Walden inversion mechanism of the fluoracetate
      dehalogenase FAcD (RPA1163) has been studied by subjecting rac-2-fluoro-2-phenyl
      acetic acid to the defluorination process. This stereochemical probe led to
      inversion of configuration in a kinetic resolution with an extremely high
      selectivity factor (E > 500), showing that the classical mechanism involving SN2
      reaction by Asp110 pertains. The high preference for the (S)-substrate is of
      synthetic value. Wide substrate scope of RPA1163 in such hydrolytic kinetic
      resolutions can be expected because the reaction of the even more sterically
      demanding rac-2-fluoro-2-benzyl acetic acid proceeded similarly. Substrate
      acceptance and stereoselectivity were explained by extensive molecular modeling
      (MM) and molecular dynamics (MD) computations. These computations were also
      applied to fluoroacetic acid itself, leading to further insights.

PMID- 28741947
TI  - A Domino Azidation/C-H Amination Approach toward Trifluoromethyl Substituted
      Imidazoles.
AB  - N-Alkyl enamines can be transformed into 2,4,5-trisubsituted imidazoles by
      reacting with (diacetoxyiodo)benzene and TMSN3 under the catalysis of a copper
      salt such as Cu(OAc)2. Tetrabutyl ammonium iodide was also capable of promoting
      the reaction. The transformation from N-alkyl enamines into 2,4,5-trisubsituted
      imidazoles took place in a domino azidation/intramolecular C(sp3)-H amination
      pattern. The present reaction provides a new efficient method for the preparation
      of 4-(trifluoromethyl) imidazoles.

PMID- 28741948
TI  - High-Pressure Phases of a S-Based Compound: Dimethyl Sulfide.
AB  - The high-pressure behavior of dimethyl sulfide was investigated at room
      temperature by Raman scattering measurements with pressures up to 30.1 GPa. Phase
      transitions at 1.3, 3.6-5.8, and 17.2 GPa were found and evidenced by the
      frequency shifts, pressure coefficients, and changes in fwhm of related modes.
      These phase transitions were suggested to result from the changes in the inter-
      and intramolecular bonding of the material. Interestingly, the CH3 groups was
      compelled to be frozen in positions at a relatively low pressure, suggested by
      the disappearance of the relative modes softening. In addition, the appearance of
      lattice mode can also be found at a modest pressure, which makes it possible to
      gain a superiority for this compound to further investigate the superconductivity
      with high transition temperatures of bulk hydrogen.

PMID- 28741949
TI  - pH Dependence of gamma-Aminobutyric Acid Iontronic Transport.
AB  - The organic electronic ion pump (OEIP) has been developed as an "iontronic" tool
      for delivery of biological signaling compounds. OEIPs rely on electrophoretically
      "pumping" charged compounds, either at neutral or shifted pH, through an ion
      selective channel. Significant shifts in pH lead to an abundance of H+ or OH-,
      which are delivered along with the intended substance. While this method has been
      used to transport various neurotransmitters, the role of pH has not been
      explored. Here we present an investigation of the role of pH on OEIP transport
      efficiency using the neurotransmitter gamma-aminobutyric acid (GABA) as the model
      cationic delivery substance. GABA transport is evaluated at various pHs using
      electrical and chemical characterization and compared to molecular dynamics
      simulations, all of which agree that pH 3 is ideal for GABA transport. These
      results demonstrate a useful method for optimizing transport of other substances
      and thus broadening OEIP applications.

PMID- 28741950
TI  - Route to 3-Amidino Indoles via Pd(II)-Catalyzed C-H Bond Activation.
AB  - We report a facile synthesis of 3-amidino indoles from indoles and cyanamides.
      The reaction is Pd(II)-catalyzed and proceeds via C-H bond activation of the
      indole in its 3-position followed by a 1,2-addition of the resulting indole
      palladium sigma-complex to a cyanamide, which provides the corresponding amidine.
      The preference for 4,5-diazafluoren-9-one (DAF) as the ligand is investigated
      using DFT calculations, and a plausible reaction pathway is presented.

PMID- 28741951
TI  - Tandem Hydroalumination/Cu-Catalyzed Asymmetric Vinyl Metalation as a New Access
      to Enantioenriched Vinylcyclopropane Derivatives.
AB  - Herein, we report the first enantio- and diastereoselective addition of
      stereodefined vinyl organometallic reagents to cyclopropenes. The operationally
      simple tandem hydroalumination and copper-catalyzed vinylmetalation allows for
      the unique access of a diverse set of enantioenriched vinylcyclopropane
      derivatives.

PMID- 28741952
TI  - An Asymmetric, Catalytic (4 + 3) Cycloaddition Reaction of Cyclopentenyl
      Oxyallylic Cations.
AB  - Treatment of 2-tosyloxycyclopentanone with substituted furans in the presence of
      a chiral amino alcohol catalyst and K2HPO4 results in the formation of (4 + 3)
      cycloaddition products with enantioselectivities that exceed 90% in certain
      cases.

PMID- 28741953
TI  - Synthesis of Functional Particles by Condensation and Polymerization of Monomer
      Droplets in Silicone Oils.
AB  - We studied the synthesis of poly(4-vinylpyridine) and poly(2-hydroxyethyl
      methacrylate) polymer particles in silicone oil using a sequential vapor phase
      polymerization method in which monomer droplets were first condensed onto a layer
      of silicone oil and subsequently polymerized via a free radical mechanism. The
      viscosity of the silicone oil was systematically varied. At lower viscosities, a
      heterogeneous particle size distribution was produced where small particles were
      formed by engulfment of the monomer droplets at the liquid surface and large
      particles were formed by coalescence of the monomer droplets inside the liquid
      layer. Coalescence could be inhibited by increasing the viscosity of the silicone
      oil leading to a decreased average radius and a narrower size distribution of the
      polymer particles. The advantages of our method for the fabrication of polymer
      particles are that it does not require surfactants or organic solvents.

PMID- 28741954
TI  - Side-Chain Modified Ergosterol and Stigmasterol Derivatives as Liver X Receptor
      Agonists.
AB  - A series of stigmasterol and ergosterol derivatives, characterized by the
      presence of oxygenated functions at C-22 and/or C-23 positions, were designed as
      potential liver X receptor (LXR) agonists. The absolute configuration of the
      newly created chiral centers was definitively assigned for all the corresponding
      compounds. Among the 16 synthesized compounds, 21, 27, and 28 were found to be
      selective LXRalpha agonists, whereas 20, 22, and 25 showed good selectivity for
      the LXRbeta isoform. In particular, 25 showed the same degree of potency as 22R
      HC (3) at LXRbeta, while it was virtually inactive at LXRalpha (EC50 = 14.51
      MUM). Interestingly, 13, 19, 20, and 25 showed to be LXR target gene-selective
      modulators, by strongly inducing the expression of ABCA1, while poorly or not
      activating the lipogenic genes SREBP1 and SCD1 or FASN, respectively.

PMID- 28741955
TI  - Synthesis, Structures, and Photophysical Properties of a Series of Rare Near-IR
      Emitting Copper(I) Complexes.
AB  - Herein, we report on the synthesis and structural characterization of a series of
      trigonal and tetrahedral cationic copper(I) complexes, bearing phosphine or N
      heterocyclic carbene ligands as donors, with benzthiazol-2-pyridine (pybt) and
      benzthiazol-2-quinoline (qybt) acting as pi-chromophores. The compounds are
      highly colored due to their 1MLCT (MLCT = metal-to-ligand charge transfer) states
      absorbing between ca. lambdaabs = 400-500 nm, with 1ILCT (ILCT = intraligand
      charge transfer) states in the UV region. The relative shifts of the S0->S1
      absorption correlate with the computed highest occupied molecular orbital-lowest
      unoccupied molecular orbital gaps, the qybt complexes generally being lower in
      energy than the pybt ones due to the larger conjugation of the quinoline-based
      ligand. The compounds exhibit, for CuI complexes, rare intense long-lived near-IR
      emission with lambdamax ranging from 593 to 757 nm, quantum yields of up to Phi =
      0.11, and lifetimes tau of several microseconds in the solid state as well as in
      poly(methyl methacrylate) films. Although a bathochromic shift of the emission is
      observed with lambdamax ranging from 639 to 812 nm and the lifetimes are greatly
      increased at 77 K, no clear indication for thermally activated delayed
      fluorescence was found, leaving us to assign the emission to originate from a
      3(Cu->pybt/qybt)MLCT state. The red to near-IR emission is a result of
      incorporation of the sulfur into the chromophore ligand, as related nitrogen
      analogues emit in the green to orange region of the electromagnetic spectrum. The
      photophysical results and conclusions have further been corroborated with density
      functional theory (DFT)/time-dependent DFT calculations, confirming the nature of
      the excited states and also the trends of the redox potentials.

PMID- 28741956
TI  - Li13Mn(SeO3)8: Lithium-Rich Transition Metal Selenite Containing Jahn-Teller
      Distortive Cations.
AB  - A novel lithium-rich transition metal selenite, Li13Mn(SeO3)8, that is composed
      of a Jahn-Teller distortive cation, Mn3+, in the high spin d4 state, and a second
      order Jahn-Teller (SOJT) distortive lone pair cation, Se4+, has been synthesized
      via hydrothermal and high temperature solid state reactions. The selenite is
      classified as a molecular compound consisting of MnO6 octahedra, SeO3 trigonal
      pyramids, and Li+ cations. Considering the Li-O interactions, the structure of
      Li13Mn(SeO3)8 may be described as a pseudo-three-dimensional framework as well.
      The title compound is thermally stable up to 500  degrees C and starts
      decomposing above the temperature attributable to the volatilization of SeO2.
      While the MnO6 octahedra in Li13Mn(SeO3)8 exhibit six identical Mn-O bond
      distances at room temperature due to the dynamic Jahn-Teller effect, a clear
      elongation of two Mn-O bonds along a specific direction is observed at 100 K. A
      series of isostructural selenites with different transition metals, i.e.,
      Li13M(SeO3)8 (M = Sc, Cr, and Fe), have been also successfully obtained in phase
      pure forms using similar synthetic methods. Magnetic properties, spectroscopic
      characterizations, and local dipole moments calculations for all the synthesized
      selenites are presented.

PMID- 28741957
TI  - Star-Shaped Polycyclic Aromatic Ketones via 3-Fold Cycloadditions of
      Isobenzofuran Trimer Equivalent.
AB  - Three-directional annulations of isobenzofuran trimer equivalent are developed.
      Importantly, the successive cycloadditions could be controlled under suitable
      conditions, selectively affording the dual or triple cycloadduct, which leads to
      the alternative preparation of the symmetrical and unsymmetrical star-shaped
      polycyclic aromatic ketones. 1H NMR analysis of the star-shaped aromatic ketone
      indicated the pi-pi interactions through the aggregation in solution.

PMID- 28741958
TI  - Observing Imperfection in Atomic Interfaces for van der Waals Heterostructures.
AB  - Vertically stacked van der Waals heterostructures are a lucrative platform for
      exploring the rich electronic and optoelectronic phenomena in two-dimensional
      materials. Their performance will be strongly affected by impurities and defects
      at the interfaces. Here we present the first systematic study of interfaces in
      van der Waals heterostructure using cross-sectional scanning transmission
      electron microscope (STEM) imaging. By measuring interlayer separations and
      comparing these to density functional theory (DFT) calculations we find that
      pristine interfaces exist between hBN and MoS2 or WS2 for stacks prepared by
      mechanical exfoliation in air. However, for two technologically important
      transition metal dichalcogenide (TMDC) systems, MoSe2 and WSe2, our measurement
      of interlayer separations provide the first evidence for impurity species being
      trapped at buried interfaces with hBN interfaces that are flat at the nanometer
      length scale. While decreasing the thickness of encapsulated WSe2 from bulk to
      monolayer we see a systematic increase in the interlayer separation. We attribute
      these differences to the thinnest TMDC flakes being flexible and hence able to
      deform mechanically around a sparse population of protruding interfacial
      impurities. We show that the air sensitive two-dimensional (2D) crystal NbSe2 can
      be fabricated into heterostructures with pristine interfaces by processing in an
      inert-gas environment. Finally we find that adopting glovebox transfer
      significantly improves the quality of interfaces for WSe2 compared to processing
      in air.

PMID- 28741959
TI  - Effect of epigallocatechin gallate on growth performance and antioxidant capacity
      in heat-stressed broilers.
AB  - This study investigated the effects of epigallocatechin gallate (EGCG) on the
      growth performance and antioxidant capacity of 35-d-old broilers exposed to heat
      stress. Broilers, 14 d of age, were divided into four groups with six replicates
      per group (eight chickens/replicate). Thermoneutral group (Group TN) was fed the
      basal diet and maintained at 28 degrees C for 24 h/d. The heat-stressed groups
      were housed at 35 degrees C for 12 h/d and 28 degrees C for 12 h/d and fed the
      basal diet supplemented with EGCG at 0, 300 and 600 mg/kg diet (Groups HS0, HS
      300 and HS600, respectively). Compared with Group TN, heat-stressed groups showed
      significantly reduced gain, feed intake and serum total protein and glucose
      levels; inhibited serum alkaline phosphatase activities; and increased serum
      levels of uric acid, cholesterol and triglycerides and the activity of serum
      creatine kinase, lactate dehydrogenase and aspartate aminotransferase (p < 0.05).
      Compared with Group HS0, Group HS600 exhibited an increased gain and feed intake;
      and normalised blood parameters and enzyme activities. Compared with Group TN,
      the expression of antioxidant-related liver proteins was decreased in Group HS0
      and increased in Groups HS300 and HS600 (p < 0.05). The results suggest that EGCG
      can improve the growth performance and alleviate the oxidant damage by modulating
      the antioxidant properties of broilers.

PMID- 28741960
TI  - Retention of Viability of Salmonella in Sucrose as Affected by Type of Inoculum,
      Water Activity, and Storage Temperature.
AB  - Outbreaks of salmonellosis have been associated with consumption of high-sugar,
      low-water activity (aw) foods. The study reported here was focused on determining
      the effect of storage temperature (5 and 25 degrees C) on survival of initially
      high and low levels of Salmonella in dry-inoculated sucrose (aw 0.26 +/- 0.01 to
      0.54 +/- 0.01) and wet-inoculated sucrose (aw 0.24 +/- 0.01 to 0.44 +/- 0.04)
      over a 52-week period. With the exception of dry-inoculated sucrose at aw 0.26,
      Salmonella survived for 52 weeks in dry- and wet-inoculated sucrose stored at 5
      and 25 degrees C. Retention of viability was clearly favored in sucrose stored at
      5 degrees C compared with 25 degrees C, regardless of level or type of inoculum
      or aw. Survival at 5 degrees C was not affected by aw. Initial high-inoculum
      counts of 5.18 and 5.25 log CFU/g of dry-inoculated sucrose (aw 0.26 and 0.54,
      respectively) stored for 52 weeks at 5 degrees C decreased by 0.56 and 0.53 log
      CFU/g; counts decreased by >4.18 and >4.25 log CFU/g in samples stored at 25
      degrees C. Inactivation rates in wet-inoculated sucrose were similar to those in
      dry-inoculated sucrose; however, a trend toward higher persistence of Salmonella
      in dry- versus wet-inoculated sucrose suggests there was a higher proportion of
      cells in the wet inoculum with low tolerance to osmotic stress. Survival patterns
      were similar in sucrose initially containing a low level of Salmonella (2.26 to
      2.91 log CFU/g). The pathogen was recovered from low-inoculated sucrose stored at
      5 degrees C for 52 weeks regardless of type of inoculum or aw and from dry
      inoculated sucrose (aw 0.54) and wet-inoculated sucrose (aw 0.24) stored at 25
      degrees C for 12 and 26 weeks, respectively. Results emphasize the importance of
      preventing contamination of sucrose intended for use as an ingredient in foods
      not subjected to a treatment that would be lethal to Salmonella.

PMID- 28741961
TI  - ISO/TC276/WG2 Biobanks and Bioresources: Draft International Standard Is Now
      Available for Comment.

PMID- 28741962
TI  - Primary pituitary tubercular abscess as a differential diagnosis for sellar
      suprasellar mass.
AB  - Only four cases of primary pituitary tubercular abscess have been reported. A 20
      year-old ladypresented to us with headache and pituitary dysfunction. Radiology
      showedsellar tubercular abscess with suprasellar extension. Microscopic
      examination of pus collected during surgery showed granulomatous tissues and Acid
      Fast Bacilli. The response to antitubercular therapy was remarkable.

PMID- 28741963
TI  - Effects of parathyroidectomy on bone metabolism in haemodialysis patients with
      secondary hyperparathyroidism.
AB  - OBJECTIVE: To evaluate the outcome of bone metabolism and bone mineral density
      (BMD) in haemodialysis patients after parathyroidectomy (PTX). METHODS: A total
      of 31 haemodialysis patients with secondary hyperparathyroidism (SHPT) were
      treated with PTX. BMD of lumbar spine (LS) and femoral neck (FN) was determined
      by dual energy X-ray absorptiometry. RESULTS: Parathyroidectomy ledds to
      significant decrease of serum beta-crosslaps (beta-CTX), osteocalcin (OC) and
      procollagen type I amino-terminal propeptide (PINP) while serum sclerostin (SOST)
      increased after surgery. BMD was markedly improved in both LS and FN after PTX. Z
      scores analysis further confirmed that PTX significantly benefited bone
      metabolism in haemodialysis patients, which well correlated with the improvement
      of serum iPTH and OC. CONCLUSIONS: Parathyroidectomy leads to significant
      improvement of serum OC, PINP, beta-CTX and SOST, which may beneficially modify
      calcium-phosphorus metabolism and BMD in haemodialysis patients with SHPT.

PMID- 28741964
TI  - Pandemics, Severity, and Context-Some Loose Ends.

PMID- 28741965
TI  - Cost-effectiveness of dolutegravir/abacavir/lamivudine in HIV-1 treatment-Naive
      (TN) patients in France.
AB  - BACKGROUND: To evaluate the cost-effectiveness of an integrase inhibitor (INI),
      dolutegravir (DTG), in combination with abacavir (ABC)/lamivudine (3TC) in
      France, in treatment-naive (TN) HIV adult patients. METHODS: The ARAMIS
      microsimulation Markov model, evaluates costs and effects of DTG vs. first-line
      ARVs options including INIs (raltegravir, elvitegravir/c), protease inhibitors
      (PIs) (darunavir/r, atazanavir/r, lopinavir/r), non-nucleoside reverse
      transcriptase inhibitors (efavirenz and rilpivirine). Efficacy and safety data
      were derived from phase III studies and network meta-analysis. Treatment
      algorithms were based on French guidelines and experts opinion. Costs included
      routine HIV and opportunistic infection care, and death. RESULTS: The model
      showed the fixed-dose combination DTG/ABC/3TC was more effective than all other
      recommended regimens: patients stayed longer on first-line, and lived longer and
      healthier. With the exception of EFV, DTG/ABC/3TC was more efficacious and less
      costly compared to all strategies. The cost per QALY gained (ICER) for DTG
      compared to EFV was ?6,939. DTG/ABC/3TC was more efficacious and less costly
      compared to INIs and PIs in all deterministic sensitivity analyses. CONCLUSION:
      DTG/ABC/3TC was cost-effective in the management of HIV TN patients in France.
      These results are mainly explained by its lower price compared to other INIs and
      PIs, DTG's superior efficacy and high barrier to resistance.

PMID- 28741967
TI  - iGlarLixi, a titratable once-daily fixed-ratio combination of basal insulin and
      lixisenatide for intensifying type 2 diabetes management for patients
      inadequately controlled on basal insulin with or without oral agents.
AB  - BACKGROUND: Achieving and maintaining glycemic control is important for people
      with type 2 diabetes (T2D), to reduce disease-related complications and
      mortality; however, about half of US patients fail to meet glycemic targets.
      iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL
      (iGlar) and lixisenatide for once-daily administration, was recently approved by
      the US Food and Drug Administration for use in adults with T2D inadequately
      controlled on basal insulin (<60 U daily) or lixisenatide. iGlar and lixisenatide
      have complementary mechanisms of action, primarily targeting fasting plasma
      glucose and postprandial plasma glucose, respectively. In the US, iGlarLixi is
      available in a 3:1 ratio of iGlar and lixisenatide, respectively, across the
      dosage range of 15-60 U of iGlar and 5-20 ug of lixisenatide. METHODS: This study
      identified phase 3 trials which assessed the efficacy and safety of iGlarLixi.
      Relevant trials were LixiLan-O, which compared iGlarLixi with iGlar or
      lixisenatide alone in insulin-naive patients, and LixiLan-L, which compared
      iGlarLixi with iGlar alone in insulin-experienced patients. RESULTS: Patients on
      iGlarLixi experienced greater A1C reduction and were more likely to achieve A1C
      <7.0% than its comparators. iGlarLixi mitigated the weight gain associated with
      iGlar without increasing hypoglycemia risk, and resulted in a lower frequency of
      gastrointestinal adverse events compared with lixisenatide. CONCLUSIONS:
      iGlarLixi provides a new approach to therapy intensification in patients with
      T2D. iGlarLixi showed greater A1C efficacy compared with either iGlar or
      lixisenatide, mitigating iGlar-associated weight gain, without increasing
      hypoglycemia risk, and reducing the gastrointestinal side-effects seen with
      lixisenatide.

PMID- 28741968
TI  - Review of adult attention-deficit/hyperactivity disorder in South Africa.
AB  - INTRODUCTION: Recently, there has been a greater focus on adults with Attention
      Deficit/Hyperactivity Disorder (ADHD) given that the symptoms persist in two
      thirds of patients into adulthood. Areas covered: A systematic review of articles
      reporting on adult ADHD in SA was undertaken. From the database search, 1209
      articles were identified, with 29 articles included in this analysis. Expert
      commentary: Fourteen of the 29 studies reviewed were exploratory, 10 were
      reviews/commentaries, four were developmental studies and one was a
      phenomenological study. More than half (58.62%) of the articles were published in
      local South African journals, 13.79% were published in African journals
      (excluding South Africa), and 27.59% of the articles were published in
      international journals. The impact factor for nine of the journals were not
      stated and the remaining 11 have impact factors ranging from 0.207 to 6.78. In
      2004, only one article on adult ADHD was published in SA and by 2015, the number
      of publications increased to six. Adult ADHD is gaining interest in South Africa,
      however, there have been a limited number of studies conducted thus far. It is
      recommended that further studies are conducted in this new and developing field.

PMID- 28741969
TI  - The importance of research literacy for yoga therapists.
AB  - Evidence-Informed Practice (EIP) utilizes the three components of expert opinion,
      research evidence, and client values. It is a recommended training competency for
      integrative health practitioners in diverse fields, such as acupuncture and
      massage therapy. Research Literacy (RL) is a necessary pre-requisite to EIP. Many
      yoga therapists have limited training in these skills, which negatively impacts
      inter-professional communication and collaboration, as well as further
      advancement of yoga therapy research and practice. In this article, we propose
      inclusion of RL and EIP in the training of yoga therapists. Benefits for client
      care, collaborative care, and the field of yoga therapy are discussed.

PMID- 28741966
TI  - The connections of Wnt pathway components with cell cycle and centrosome: side
      effects or a hidden logic?
AB  - Wnt signaling cascade has developed together with multicellularity to orchestrate
      the development and homeostasis of complex structures. Wnt pathway components -
      such as beta-catenin, Dishevelled (DVL), Lrp6, and Axin-- are often dedicated
      proteins that emerged in evolution together with the Wnt signaling cascade and
      are believed to function primarily in the Wnt cascade. It is interesting to see
      that in recent literature many of these proteins are connected with cellular
      functions that are more ancient and not limited to multicellular organisms - such
      as cell cycle regulation, centrosome biology, or cell division. In this review,
      we summarize the recent literature describing this crosstalk. Specifically, we
      attempt to find the answers to the following questions: Is the response to Wnt
      ligands regulated by the cell cycle? Is the centrosome and/or cilium required to
      activate the Wnt pathway? How do Wnt pathway components regulate the centrosomal
      cycle and cilia formation and function? We critically review the evidence that
      describes how these connections are regulated and how they help to integrate cell
      to-cell communication with the cell and the centrosomal cycle in order to achieve
      a fine-tuned, physiological response.

PMID- 28741970
TI  - Efficacy and safety of once-weekly semaglutide for the treatment of type 2
      diabetes.
AB  - INTRODUCTION: Type 2 diabetes is a chronic metabolic disease characterized by
      persistent hyperglycemia resulting from progressive deficient of insulin in
      patients with a background of insulin resistance. Current treatment algorithms
      recommended by American Diabetes Association/The European Association for the
      Study of Diabetes promote a patient-centered approach that takes into account a
      comprehensive consideration of pharmacological properties of drugs, including
      glucose-lowering action, effects on body weight, correction on multiple
      pathophysiologic defects, tolerability, and long-term safety. Glucagon
      likepeptide1 (GLP-1) receptor analogues are appealing due to the improved
      glycemic control in a glucose-dependent manner, modest weight loss and low risk
      of hypoglycemia. Areas covered: Semaglutide (Novo Nordisk), a once-weekly GLP-1
      analogue, is currently in the phase III clinical trial for the treatment of type
      2 diabetes. This article aims to review the pharmacological and clinical profiles
      of semaglutide based on the available clinical data. Expert opinion: Semaglutide
      achieved greater reduction from baseline in HbA1c in comparison to placebo. The
      greater proportion of patients in semaglutide group than that in placebo group
      achieved target HbA1c <7.0% and <6.5%, respectively. Semaglutide is the second
      GLP-1 analogue contributing to the reduced bodyweight and improving obesity
      related complications. More importantly, semaglutide is beneficial to diabetic
      patients with high cardiovascular risk according to the recently completed phase
      III trial. The incidence of gastrointestinal adverse effects increased with
      semaglutide dose.

PMID- 28741971
TI  - Five patients who died during treatment for adult Still's disease.

PMID- 28741972
TI  - The effect of zirconium doping of cerium dioxide nanoparticles on pulmonary and
      cardiovascular toxicity and biodistribution in mice after inhalation.
AB  - Development and manufacture of nanomaterials is growing at an exponential rate,
      despite an incomplete understanding of how their physicochemical characteristics
      affect their potential toxicity. Redox activity has been suggested to be an
      important physicochemical property of nanomaterials to predict their biological
      activity. This study assessed the influence of redox activity by modification of
      cerium dioxide nanoparticles (CeO2 NPs) via zirconium (Zr) doping on the
      biodistribution, pulmonary and cardiovascular effects in mice following
      inhalation. Healthy mice (C57BL/6 J), mice prone to cardiovascular disease (ApoE
      /-, western-diet fed) and a mouse model of neurological disease (5 * FAD) were
      exposed via nose-only inhalation to CeO2 NPs with varying amounts of Zr-doping
      (0%, 27% or 78% Zr), or clean air, over a four-week period (4 mg/m3 for 3 h/day,
      5 days/week). Effects were assessed four weeks post-exposure. In all three mouse
      models CeO2 NP exposure had no major toxicological effects apart from some modest
      inflammatory histopathology in the lung, which was not related to the amount of
      Zr-doping. In ApoE-/- mice CeO2 did not change the size of atherosclerotic
      plaques, but there was a trend towards increased inflammatory cell content in
      relation to the Zr content of the CeO2 NPs. These findings show that subacute
      inhalation of CeO2 NPs causes minimal pulmonary and cardiovascular effect four
      weeks post-exposure and that Zr-doping of CeO2 NPs has limited effect on these
      responses. Further studies with nanomaterials with a higher inherent toxicity or
      a broader range of redox activities are needed to fully assess the influence of
      redox activity on the toxicity of nanomaterials.

PMID- 28741973
TI  - Characteristics of functional impairment in patients with long-standing
      rheumatoid arthritis based on range of motion of joints: Baseline data from a
      multicenter prospective observational cohort study to evaluate the effectiveness
      of joint surgery in the treat-to-target era.
AB  - OBJECTIVE: To explore the characteristics of functional impairment in patients
      with established rheumatoid arthritis (RA) based on the range of motion (ROM) of
      joints in a prospective observational study of RA patients undergoing joint
      surgery. METHODS: We collected data on demographics, Health Assessment
      Questionnaire Disability Index (HAQ-DI), and the ROM of large joints including
      the shoulder, elbow, wrist, hip, knee, and ankle. Associations between the ROM of
      each joint and disability in the eight HAQ-DI categories were determined using
      receiver operating characteristic (ROC) and logistic regression analyses. ROM cut
      off values of each joint for the absence of disability in each HAQ-DI category
      were determined using ROC curves. RESULTS: A total of 460 patients were enrolled
      and analyzed in this study. Based on ROC analysis, the ROM of each joint was
      significantly associated with disability in each category. After adjusting for
      disease activity, age, and sex, shoulder abduction had the highest independent
      impact on disability in activity [cut-off: 139 degrees (OR: 5.26)], elbow flexion
      extension in dressing [121 degrees (OR: 2.22)], wrist flexion-extension in reach
      [86 degrees (OR: 2.71)], hip flexion-extension in walking [126 degrees (OR:
      3.42)], and knee flexion-extension in walking [134 degrees (OR: 2.97)].
      CONCLUSIONS: Limited ROM of multiple joints was significantly associated with
      functional impairment in patients with long-standing RA. Motion in daily activity
      involves multiple joints, and at least two joints were independently involved in
      disability.

PMID- 28741974
TI  - Sarcopenia and physical function are associated with inflammation and
      arteriosclerosis in community-dwelling people: The Yakumo study.
AB  - OBJECTIVES: Sarcopenia reduces physical function, while chronic inflammation
      causes arteriosclerosis and decreases skeletal muscle. We conducted a cross
      sectional study to elucidate the associations among sarcopenia, physical
      function, arteriosclerosis, and inflammation in community-dwelling people.
      METHODS: We recruited 335 participants in an annual health checkup. We diagnosed
      sarcopenia based on appendicular skeletal muscle mass index (aSMI) assessed by
      bioelectrical impedance analysis. We measured several physical function tests,
      blood pressure, and serum levels of high-sensitivity C-reactive protein (hs-CRP),
      total cholesterol, and low-density lipoprotein cholesterol. RESULTS: After
      controlling for age, sex, and BMI, participants in the sarcopenia group showed
      lower performance in all measured physical tests than the normal group.
      Arteriosclerosis risk factors, including blood pressure, cholesterol levels, and
      hs-CRP, were significantly higher in the sarcopenia group than in the normal
      group. hs-CRP and total cholesterol levels were significant risk factors of
      sarcopenia. The aSMI, grip strength, and maximum stride length were negatively
      related to hs-CRP level. CONCLUSIONS: Community-dwelling people with sarcopenia
      had higher levels of hs-CRP and a higher risk for arteriosclerosis. The serum
      level of hs-CRP was an independent risk factor for sarcopenia and was associated
      with physical function. These findings indicate that chronic inflammation may
      relate arteriosclerosis and sarcopenia simultaneously.

PMID- 28741975
TI  - Antibiotic switch during treatment with antibiotics against respiratory tract
      infections in ambulatory care in Norway.
AB  - OBJECTIVES: To compare antibiotic treatment failure evaluated as switch from one
      type of antibiotics to another in ambulatory care. METHODS: Data on all dispensed
      doxycycline, amoxicillin, phenoxymethylpenicillin and macrolides in Norway June
      2013 - May 2015, was retrieved from the Norwegian Prescription Database. We
      computed switch rates for the selected antibiotics on day 1-28 after initial
      dispensing, and the corresponding odds-ratios, adjusted for patients' age and
      gender, and prescribers' specialty. RESULTS: Of 1.860.036 dispensed antibiotics,
      103.076 (5.5%) were switched within 28 days. Within 10 days after the index date,
      the switch rate was highest for phenoxymethylpenicillin (4.1%), followed by
      amoxicillin (2.5%), macrolides and doxycycline (2.2%). CONCLUSIONS: The switch
      rate after initial dispensing of phenoxymethylpenicillin is higher than that of
      more broad-spectrum antibiotics. However, it is still low, supporting the
      recommendation of phenoxymethylpenicillin as first line treatment when an
      antibiotic is indicated for a respiratory tract infection in primary care.

PMID- 28741976
TI  - Fampridine response in MS patients with gait impairment in a real-world setting:
      Need for new response criteria?
AB  - OBJECTIVE: The primary objective of this real-world study was to describe the
      response to fampridine and changes of gait parameters in multiple sclerosis (MS)
      patients' walking disability (Expanded Disability Status Scale (EDSS): 4-7) after
      treatment with fampridine for 2 weeks as recommended by the European Medicines
      Agency (EMA) and compare it with the overall physician's judgement. METHODS: A
      total of 211 adult MS patients were analyzed using a multimodal gait assessment
      including the timed 25-foot walk test (T25FW), 2-minute walking test (2-MWT), 12
      item Multiple Sclerosis Walking Scale (MSWS-12), the GAITRite electronic walkway
      system, and the patients' clinical global impression (CGI). Multimodal gait
      assessment was compared with the clinician's impression of overall improvement
      after 2 weeks. RESULTS: In total, 189 subjects were included, of which 133
      (70.37%) were responders to fampridine (RF), according to physician's judgement.
      Looking at independent multimodal gait assessment, RFs showed improvement of
      12.60% in the T25FW, 19.25% in the 2-MWT, 21.12% in the MSWS-12, and 6.54% in
      their Functional Ambulation Profile (FAP) score. The combination of the T25FW and
      the MSWS-12 would offer the best sensitivity and specificity for determining
      response to fampridine according to both neurologists' and patients'
      classification. CONCLUSION: This study provides new information on the use of
      fampridine in a real-world setting with a large patient sample on the potential
      benefit of using more definitive responder criteria to fampridine for the
      clinical setting.

PMID- 28741977
TI  - Reduction in the presence of cryoglobulins over time in the hemodialysis
      treatment.
AB  - BACKGROUND: The presence of cryoglobulins in patients with chronic kidney disease
      (CKD) on hemodialysis is well described. However, the generation of cryoglobulins
      during the dialysis treatment has yet to be established. The aim of the present
      study was to determine the presence of serum cryoglobulins over time in the
      dialysis treatment in patients with CKD not infected with hepatitis C virus
      (HCV). METHOD: Peripheral blood samples were collected at the beginning of
      dialysis treatment and at 30, 60, 90 and 120 days afterwards. Cryoglobulins were
      defined by the presence of immunocomplexes that precipitated in vitro with
      exposure to cold and resolubilized when rewarmed. The components of the
      cryoprecipitate were analyzed by radial immunodiffusion. RESULTS: In this study,
      14 patients were included: 11 male and three female, aged 28-88 years, with mean
      time on hemodialysis of 57 +/- 36 days at baseline. The presence of cryoglobulin,
      constituted by IgM, IgA, IgG and the C3 and C4 components of the complement, was
      observed in the serum of all patients at the beginning of hemodialysis. Sequence
      analyses showed that the amount of cryoprecipitate decreased during the dialysis
      treatment. CONCLUSION: There was a high prevalence of mixed cryoglobulins in CKD
      patients at the beginning of hemodialysis, and the amount of cryoprecipitate
      decreased during the treatment.

PMID- 28741978
TI  - Effects of co-exposure to atrazine and ethanol on the oxidative damage of kidney
      and liver in Wistar rats.
AB  - Both ethanol (EtoH) and atrazine (ATZ) have hepatic and nephro-toxic effects in
      rats. In the present study, the toxicity of EtoH (5 g kg-1) on the kidney and
      liver in the absence or in the presence of different doses of ATZ (50, 100, 300
      mg kg-1) was evaluated after 21 days in rats. Results showed that the mixture
      effects on catalase and superoxide dismutase activities were more severe in both
      tissues compared to EtoH alone, especially as the dose of ATZ was increased.
      Hepatic malondialdehyde level (an index of lipid peroxidation) was increased from
      20.32% in the EtoH +50 mg kg-1 ATZ-treated rats to 34% in the EtoH +300 mg kg-1
      ATZ-treated rats compared to the EtoH values. Renal malondialdehyde values remain
      as high as 81% in the EtoH-treated rats and the different combine exposure
      groups. Furthermore, as the dose of ATZ in the mixture was increased, serum uric
      acid level increased compared to the EtoH values. When the EtoH +300 mg kg-1 ATZ
      animals were pretreated with curcumin (an antioxidant), the histopathological
      changes and peroxidative damages in both tissues were blocked. The exposure of
      EtoH-treated rats to ATZ enhanced renal and hepatic peroxidative damages in rats.

PMID- 28741979
TI  - Systematic review of the literature on triclosan and health outcomes in humans.
AB  - The ability of epidemiologic evidence to inform regulatory decisions is largely
      dependent on the coherence and quality of the published literature. This
      systematic review examines the quality and consistency of studies assessing
      health outcomes associated with exposure to triclosan (TCS), an antimicrobial
      chemical with a short physiologic half-life. We used elements of the
      Biomonitoring, Environmental Epidemiology, and Short-Lived Chemicals instrument
      to evaluate aspects of study quality. Each methodological domain - overall
      design, exposure assessment, and data analysis - was categorized according to
      three tiers where Tier 1 indicated the highest quality. We also examined
      consistency of methods, results and reporting as considerations for weight of
      evidence (WOE) assessment. Studies were considered sufficiently comparable if
      they addressed the same or similar research questions. Forty-two studies met the
      criteria for inclusion. Only one randomized cross-over clinical trial of TCS was
      assigned to Tier 1 for all three domains. Most other studies were assigned to
      Tier 3 for at least one domain. Although the available literature examined more
      than 100 different health endpoints and reported hundreds of different measures
      of association, few studies were considered comparable. For reported measures of
      association, most were not significantly different from the null; the few
      statistically significant results represented isolated findings without a
      discernable across- or within-study pattern. We conclude that the current body of
      epidemiologic literature does not allow a meaningful WOE assessment due to
      methodological limitations of individual studies and lack of inter-study
      consistency. On the other hand, methodologically stronger studies may be used to
      inform future research.

PMID- 28741980
TI  - Intermittent drug holidays in fingolimod therapy for multiple sclerosis.

PMID- 28741981
TI  - Functional Smiles: Tools for Love, Sympathy, and War.
AB  - A smile is the most frequent facial expression, but not all smiles are equal. A
      social-functional account holds that smiles of reward, affiliation, and dominance
      serve basic social functions, including rewarding behavior, bonding socially, and
      negotiating hierarchy. Here, we characterize the facial-expression patterns
      associated with these three types of smiles. Specifically, we modeled the facial
      expressions using a data-driven approach and showed that reward smiles are
      symmetrical and accompanied by eyebrow raising, affiliative smiles involve lip
      pressing, and dominance smiles are asymmetrical and contain nose wrinkling and
      upper-lip raising. A Bayesian-classifier analysis and a detection task revealed
      that the three smile types are highly distinct. Finally, social judgments made by
      a separate participant group showed that the different smile types convey
      different social messages. Our results provide the first detailed description of
      the physical form and social messages conveyed by these three types of functional
      smiles and document the versatility of these facial expressions.

PMID- 28741982
TI  - Multimodal MR Imaging Signatures of Cognitive Impairment in Active Professional
      Fighters.
AB  - Purpose To investigate whether combining multiple magnetic resonance (MR) imaging
      modalities such as T1-weighted and diffusion-weighted MR imaging could reveal
      imaging biomarkers associated with cognition in active professional fighters.
      Materials and Methods Active professional fighters (n = 297; 24 women and 273
      men) were recruited at one center. Sixty-two fighters (six women and 56 men)
      returned for a follow-up examination. Only men were included in the main analysis
      of the study. On the basis of computerized testing, fighters were separated into
      the cognitively impaired and nonimpaired groups on the basis of computerized
      testing. T1-weighted and diffusion-weighted imaging were performed, and volume
      and cortical thickness, along with diffusion-derived metrics of 20 major white
      matter tracts were extracted for every subject. A classifier was designed to
      identify imaging biomarkers related to cognitive impairment and was tested in the
      follow-up dataset. Results The classifier allowed identification of seven imaging
      biomarkers related to cognitive impairment in the cohort of active professional
      fighters. Areas under the curve of 0.76 and 0.69 were obtained at baseline and at
      follow-up, respectively, with the optimized classifier. The number of years of
      fighting had a significant (P = 8.8 * 10-7) negative association with fractional
      anisotropy of the forceps major (effect size [d] = 0.34) and the inferior
      longitudinal fasciculus (P = .03; d = 0.17). A significant difference was
      observed between the impaired and nonimpaired groups in the association of
      fractional anisotropy in the forceps major with number of fights (P = .03, d =
      0.38) and years of fighting (P = 6 * 10-8, d = 0.63). Fractional anisotropy of
      the inferior longitudinal fasciculus was positively associated with psychomotor
      speed (P = .04, d = 0.16) in nonimpaired fighters but no association was observed
      in impaired fighters. Conclusion Without enforcement of any a priori assumptions
      on the MR imaging-derived measurements and with a multivariate approach, the
      study revealed a set of seven imaging biomarkers that were associated with
      cognition in active male professional fighters. (c) RSNA, 2017 Online
      supplemental material is available for this article.

PMID- 28741983
TI  - 'Taking care' in the age of AIDS: older rural South Africans' strategies for
      surviving the HIV epidemic.
AB  - Older adults have been largely overlooked in community studies of HIV in highly
      endemic African countries. In our rural study site in Mpumalanga Province, South
      Africa, HIV prevalence among those aged 50 and older is 16.5%, suggesting that
      older adults are at risk of both acquiring and transmitting HIV. This paper
      utilises community-based focus-group interviews with older rural South African
      men and women to better understand the normative environment in which they come
      to understand and make decisions about their health as they age in an HIV endemic
      setting. We analyse the dimensions of an inductively emerging theme: ku ti
      hlayisa (to take care of yourself). For older adults, 'taking care' in an age of
      AIDS represented: (1) an individualised pathway to achieving old-age
      respectability through the taking up of responsibilities and behaviours that
      characterise being an older person, (2) a set of gendered norms and strategies
      for reducing one's HIV risk, and (3) a shared responsibility for attenuating the
      impact of the HIV epidemic in the local community. Findings reflect the
      individual, interdependent and communal ways in which older rural South Africans
      understand HIV risk and prevention, ways that also map onto current
      epidemiological thinking for improving HIV-related outcomes in high-prevalence
      settings.

PMID- 28741984
TI  - Multiple CT Scans Extend Lifespan by Delaying Cancer Progression in Cancer-Prone
      Mice.
AB  - Computed tomography (CT) scans are a routine diagnostic imaging technique that
      utilize low-energy X rays with an average absorbed dose of approximately 10 mGy
      per clinical whole-body CT scan. The growing use of CT scans in the clinic has
      raised concern of increased carcinogenic risk in patients exposed to ionizing
      radiation from diagnostic procedures. The goal of this study was to better
      understand cancer risk associated with low-dose exposures from CT scans.
      Historically, low-dose exposure preceding a larger challenge dose increases tumor
      latency, but does little to impact tumor frequency in Trp53+/- mice. To assess
      the effects of CT scans specifically on tumor progression, whole-body CT scans
      (10 mGy/scan, 75 kVp) were started at four weeks after 4 Gy irradiation, to allow
      for completion of tumor initiation. The mice were exposed to weekly CT scans for
      ten consecutive weeks. In this study, we show that CT scans modify cellular end
      points commonly associated with carcinogenesis in cancer-prone Trp53+/-
      heterozygous mice. At five days after completion of CT scan treatment, the
      multiple CT scans did not cause detectable differences in bone marrow genomic
      instability, as measured by the formation of micronucleated reticulocytes and
      H2AX phosphorylation in lymphoid-type cells, and significantly lowered
      constitutive and radiation induced levels of apoptosis. The overall lifespan of 4
      Gy exposed cancer-initiated mice treated with multiple CT scans was increased by
      approximately 8% compared to mice exposed to 4 Gy alone (P < 0.017). Increased
      latency periods for lymphoma and sarcoma (P < 0.040) progression contributed to
      the overall increase in lifespan. However, repeated CT scans did not affect
      carcinoma latency. To our knowledge, this is the first reported study to show
      that repeated CT scans, when administered after tumor initiation, can improve
      cancer morbidity by delaying the progression of specific types of radiation
      induced cancers in Trp53+/- mice.

PMID- 28741985
TI  - The influence of fasudil on renal proximal tubular cell epithelial-mesenchymal
      transition induced by parathormone.
AB  - BACKGROUND: Renal fibrosis is a common pathway through which a variety of chronic
      kidney diseases progress to end-stage renal disease. Epithelial-mesenchymal
      transition (EMT) of renal proximal tubular cells is one of the most important
      factors in renal fibrosis. This study investigates if fasudil could influence EMT
      of renal proximal tubular cells. METHODS: HK-2 cells in passage 3-4 were used for
      all experiments. The cells were divided into five groups and treated with
      different concentrations of PTH and then observe cellular morphological changes
      at 0, 24 and 48 h using an inverted microscope and investigate the expression of
      the epithelial cell marker E-cadherin and the renal fibroblast marker alpha
      smooth muscle actin (alpha-SMA). RESULTS: PTH significantly induced EMT, fasudil
      inhibited EMT induced by PTH to different degrees, and the inhibitory effect of
      fasudil was most pronounced at 20 MUmol/L. CONCLUSION: Monitoring PTH levels,
      early prevention and control of hyperparathyroidism and reducing the
      concentration of PTH are important means to improve prognosis and delay the
      progression of chronic kidney disease. Fasudil can restrain EMT induced by PTH;
      this conclusion provides experimental data for the application of fasudil in the
      clinical prevention and treatment of renal fibrosis.

PMID- 28741986
TI  - Serum ferritin as an activity marker for granulamotosis with polyangiitis.
AB  - BACKGROUND: Serum ferritin correlates well with the activities of systemic lupus
      erythematosus (SLE) and dermatomyositis, but it has not been previously studied
      in patients with vasculitis. METHODS: Medical records of granulomatosis with
      polyangiitis (GPA, Wegener's granulomatosis) patients with at least six months of
      regular follow-up were evaluated. The activity of GPA was assessed with
      Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG).
      Serum ferritin and other acute phase markers were measured at initial
      presentation. RESULTS: Serum ferritin levels were found to be the highest in GPA
      patients with alveolar hemorrhage, median (IQR) 1041 (1281) MUg/L. Patients with
      renal disease also had high levels of ferritin and it was correlated with
      concurrent glomerular filtration rate (r = -0.65, p < .001). Serum ferritin is
      also correlated well with the BVAS/WG scores (r = 0.79, p < .001). CONCLUSIONS:
      Measurement of serum ferritin might help in assessing disease activity of GPA.

PMID- 28741987
TI  - Multimodal characterization of gray matter alterations in neuromyelitis optica.
AB  - OBJECTIVE: To investigate structural and functional alterations of gray matter
      (GM) and examine their clinical relevance in neuromyelitis optica (NMO) using
      multimodal magnetic resonance imaging (MRI) techniques. METHODS: A total of 35
      NMO and 36 healthy controls (HC) were recruited in this study. Cortical lesions
      were investigated by double inversion recovery technique. Five voxel-wise MRI
      measurements were obtained for each participant in the GM including gray matter
      volume (GMV), fractional anisotropy (FA), mean diffusivity (MD), amplitude of low
      frequency fluctuation (ALFF), and weighted functional connectivity strength
      (wFCS). Between-group differences, cross-modality relationships, and MRI-clinical
      correlations were examined. RESULTS: No cortical lesions were found in NMO.
      Compared to HC, NMO patients exhibited significantly decreased GMV in deep GM and
      cortical regions involving visual function and cognition. Diffusion GM
      abnormalities were widespread in the patients. Decreased ALFF and wFCS were
      observed in the patients in sensorimotor, visual, cognition, and cerebellar
      sites. GM structural alterations were correlated with cognitive but not physical
      disability scores of the patients. CONCLUSION: Despite the lack of focal cortical
      lesions, patients with NMO exhibit both structural and functional alterations of
      GM in cerebrum and cerebellum that predominantly involve deep GM, visual, motor,
      and cognitive regions. GM alterations are associated with cognitive impairment
      but not physical disability.

PMID- 28741988
TI  - Comparison of Quality of Life in Patients with beta-Thalassemia Intermedia and
      beta-Thalassemia Major in Southern Iran.
AB  - Increased life expectancy in patients with beta-thalassemia (beta-thal) requires
      healthcare professionals to give greater attention to improving their quality of
      life (QoL). We aimed to evaluate health-related QoL (HRQoL) and its determinants
      in patients with beta-thal intermedia (beta-TI) compared with beta-thal major
      (beta-TM). In this cross sectional study, 118 patients with beta-TI, referred to
      the Thalassemia Clinic of Shiraz University of Medical Sciences, Shiraz, Iran,
      were investigated by convenience sampling from January to June 2014 in southern
      Iran. A Short Form-36 (SF36) questionnaire was used. We had previously conducted
      a similar study in 101 patients with beta-TM (12 to 38 years). Compared data of
      the two studies were analyzed. Mean age was 26.5 +/- 6.5 (12 to 48) years in beta
      TI and 19.5 +/- 4.4 (12-38) years in the beta-TM group. The best scales of HRQoL
      were physical functionin (PF) (76.8 +/- 26.6) and bodily pain (BP) (70.1 +/-
      24.8) in the beta-TI group. Males had significantly better score only in vitality
      dimension compared to females (p = 0.020). Higher education (p = 0.023) in
      univariate analysis and age <=20 years (B coefficient = 13, p = 0.008) in
      multivariate analysis showed significant relationships with higher total HRQoL
      score in beta-TI. Comparison of beta-TI and beta-TM, after adjusting for
      covariates, total HRQoL was similar between the two groups. In evaluating the
      subscales, only PF showed a better condition in patients with beta-TM [adjusted
      mean difference = 12.5, 95% confidence interval (95% CI): 5.6-19.3, p < 0.0001].
      Contrary to our expectations, QoL in patients with beta-TI were not better than
      beta-TM. Training programs and psychosocial support of all patients with beta-TI
      and beta-TM as well as their care providers with more focus on older patients,
      females and the patients with lower educational degree should be taken into
      account.

PMID- 28741989
TI  - Mithramycin has inhibitory effects on gliostatin and matrix metalloproteinase
      expression induced by gliostatin in rheumatoid fibroblast-like synoviocytes.
AB  - OBJECTIVES: Gliostatin (GLS) has angiogenic and arthritogenic activities and
      enzymatic activity as thymidine phosphorylase. Aberrant GLS production has been
      observed in the synovial membranes of patients with rheumatoid arthritis (RA).
      Matrix metalloproteinases (MMPs) are involved in joint destruction. Promoters of
      GLS and some MMP genes contain Sp1 binding sites. We examined the inhibitory
      effect of the Sp1 inhibitor mithramycin on GLS-induced GLS and MMP expression in
      cultured fibroblast-like synoviocytes (FLSs). METHODS: Synovial tissue samples
      were obtained from patients with RA. FLSs pretreated with mithramycin were
      cultured with GLS. The mRNA expression levels of GLS and MMP-1, MMP-2, MMP-3, MMP
      9, and MMP-13 were determined using reverse transcription polymerase chain
      reactions. Protein levels were measured using enzyme immunoassay and gelatin
      zymography. RESULTS: GLS upregulated the expression of GLS itself and of MMP-1,
      MMP-3, MMP-9, and MMP-13, an effect significantly reduced by treatment with
      mithramycin. GLS and mithramycin had no effect on MMP-2 expression. CONCLUSIONS:
      Mithramycin downregulated the increased expression of GLS and MMP-1, MMP-3, MMP
      9, and MMP-13 in FLSs treated with GLS. Because GLS plays a pathological role in
      RA, blocking GLS stimulation using an agent such as mithramycin may be a novel
      approach to antirheumatic therapy.

PMID- 28741990
TI  - Novosphingobium fontis sp. nov., isolated from a spring.
AB  - A bacterial strain designated STM-14T was isolated from a spring in Taiwan and
      characterized using a polyphasic taxonomic approach. Strain STM-14T was a Gram
      stain-negative, aerobic, poly-beta-hydroxybutyrate-accumulating, non-motile, rod
      shaped bacterium and formed cream-coloured colonies. Strain STM-14T grew at 15-37
      degrees C (optimum, 30  degrees C), at pH 5.0-9.0 (optimum, pH 6.0) and with 0
      0.5 % (w/v) NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene
      sequences showed that strain STM-14T belonged to the genus Novosphingobium and
      showed the highest levels of sequence similarity to Novosphingobium naphthae D39T
      (98.5 %) and Novosphingobium mathurense SM117T (97.6 %). The major fatty acids
      (>10 %) of strain STM-14T were C17 : 1omega6c, summed feature 3 (C16 : 1omega7c
      and/or C16 : 1omega6c), C18 : 1omega7c, C15 : 0 2-OH and C17 : 1omega8c. The
      polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine,
      diphosphatidylglycerol, phosphatidyldimethylethanolamine, sphingoglycolipid,
      phosphatidylcholine and several uncharacterized lipids. The major polyamine was
      spermidine. The major isoprenoid quinone was Q-10. The DNA G+C content was 66.6
      mol%. The DNA-DNA hybridization value for strain STM-14T with N. naphthae JCM
      31158T and N. mathurense DSM 23374T was less than 49 %. Differential phenotypic
      properties, together with the phylogenetic inference, demonstrate that strain STM
      14T should be classified as representing a novel species of the genus
      Novosphingobium, for which the name Novosphingobium fontis sp. nov. is proposed.
      The type strain is STM-14T (=BCRC 80924T=LMG 29290T=KCTC 42983T).

PMID- 28741991
TI  - Meira siamensis sp. nov., a novel anamorphic ustilaginomycetous yeast species
      isolated from the vetiver grass phylloplane.
AB  - Two strains, DMKU-LV83 and DMKU-LV85, of a novel yeast species were isolated from
      the phylloplane of vetiver grass collected in Thailand by plating of leaf
      washings. Analysis of the sequences of the D1/D2 region of the large subunit
      (LSU) rRNA gene showed that the two strains represent a single novel species and
      most closely related to Meira miltonrushii. However, the novel species differed
      from the type strain of M. miltonrushii (MCA 3882T) by 5.5 % nucleotide
      substitutions in the D1/D2 region and 8.9 % nucleotide substitutions in the ITS
      region. The phylogenetic analysis based on the D1/D2 region of the LSU rRNA gene
      confirmed the placement of the novel species in the Meira clade and its close
      affinity with M. miltonrushii. Therefore, the species Meira siamensis sp. nov. is
      proposed. The type strain is DMKU-LV83T (=CBS 12860T=BCC 61180T).

PMID- 28741992
TI  - Herpetosiphon gulosus sp. nov., a filamentous predatory bacterium isolated from
      sandy soil and Herpetosiphon giganteus sp. nov., nom. rev.
AB  - Three filamentous gliding bacteria from the German Collection of Microorganisms
      and Cell Cultures, Hp g11, Hp g471 and Hp g472, were subjected to a phylogenetic
      analysis. These organisms had previously been classified as members of the genus
      Herpetosiphon based on their growth physiology and morphology. However, a
      taxonomic assignment at the species level had not been carried out. Analysis of
      16S rRNA sequences now confirmed the close relationship of strain Hp g472 to
      Herpetosiphon aurantiacus DSM 785T (98.6 % nucleotide identity) and Herpetosiphon
      geysericola DSM 7119T (97.7 %). The results of DNA-DNA hybridization experiments
      further implied that strain Hp g472 should be classified as a distinct species.
      The DNA G+C content of strain Hp g472 was 49.9 mol%. The major quinone was MK-10
      and the predominant cellular fatty acids were C18 : 1, C16 : 1 and C16 : 0. Based
      on phenotypic, chemotaxonomic and phylogenetic data it was concluded that strain
      Hp g472 represents a novel species of the genus Herpetosiphon, for which the name
      Herpetosiphon gulosus sp. nov. is proposed. The type strain is Hp g472T (=DSM
      52871T=NBRC 112829T). In contrast to Hp g472T, the strains Hp g11 and Hp g471
      exhibited closest 16S rRNA gene sequence similarity (>99 %) with 'Herpetosiphon
      giganteus' Hp a2. The distinctive genotypic and phenotypic properties of the
      latter supported the revival of the name as Herpetosiphon giganteus (ex
      Reichenbach & Golecki, 1975) sp. nov., nom. rev. We propose the previously
      deposited reference strain DSM 589T=NBRC 112828T as the type strain.

PMID- 28741993
TI  - Muricauda marina sp. nov., isolated from marine snow of Yellow Sea.
AB  - A Gram-staining-negative, long rod-shaped, non-motile, strictly aerobic bacterial
      strain, designated H19-56T, was isolated from a surface marine snow sample
      collected from the Yellow Sea near China. Phylogenetic analysis based on 16S rRNA
      gene sequences indicated that H19-56T represented a member of the genus Muricauda
      and showed the highest sequence similarity to Muricauda ruestringensis B1T (96.9
      %). H19-56T grew optimally at pH 8.0, 32  degrees C and in the presence of 3 %
      (w/v) NaCl. The DNA G+C content was 43.6 mol%. H19-56T contained MK-6 as the
      predominant respiratory quinone and had iso-C15 : 0 and iso-C15 : 1G as the major
      cellular fatty acids. The major polar lipids were phosphatidylethanolamine, two
      unidentified aminolipids and three unidentified lipids. On the basis of the
      results of the polyphasic analyses, this isolate was considered to represent a
      novel species of the genus Muricauda, for which the name Muricauda marina sp.
      nov. is proposed. The type strain is H19-56T (CGMCC 1.15774T=JCM 31456T=MCCC
      1K03196T=KCTC 52374T).

PMID- 28741994
TI  - Perlucidibaca aquatica sp. nov., isolated from fresh water.
AB  - A Gram-staining-negative, non-motile, non-pigmented, strictly aerobic and rod
      shape bacterium, designated BK296T, was isolated from stream water originating
      from a limestone cave in Samcheok, Korea. Optimal growth of strain BK296T was
      observed at 30  degrees C, pH 7.0-8.0 and without NaCl. Phylogenetic analysis
      based on 16S rRNA gene sequences showed that strain BK296T belonged to the genus
      Perlucidibaca, forming a robust clade with a member of the genus, and was most
      closely related to Perlucidibaca piscinae (97.8 %). The average nucleotide
      identity value between strain BK296T and Perlucidibacapiscinae IMCC1704T was 79.8
      %, and the genome-to-genome distance was 17.5 % on mean. The G+C content of the
      DNA of strain BK296T was 55.7 mol%. The major fatty acids were summed feature 3
      (C16 : 1omega7c and/or C16 : 1omega6c), C16 : 0, C12 : 0 3-OH and summed feature
      8 (C18 : 1omega7c and/or C18 : 1omega6c). The major isoprenoid quinone was
      ubiquinone Q-8. On the basis of phenotypic, genotypic and phylogenetic analyses,
      strain BK296T (=KCTC 52162T=JCM 31377T) represents a novel species of the genus
      Perlucidibaca, for which the name Perlucidibaca aquatica sp. nov. is proposed.

PMID- 28741995
TI  - Merdimonas faecis gen. nov., sp. nov., isolated from human faeces.
AB  - A strictly anaerobic Gram-stain-positive, non-motile and non-spore-forming
      bacterial strain, BR31T, was isolated from a faecal sample of a healthy human.
      Bacterial colonies were ivory-coloured on GAM agar and composed of rod-shaped
      cells with rounded ends approximately 1.4-2.1*0.5-0.6 um in size. According to
      comparative analysis based on 16S rRNA gene sequences, strain BR31T formed a
      distinct phylogenetic lineage that reflects a new genus within Clostridium
      cluster XIVa in the family Lachnospiraceae, with highest similarity to
      Eubacterium contortum DSM 3982T (94.6 %). The DNA G+C content was calculated to
      be 47.0 mol% from whole genome sequencing. Predicted genes associated with
      synthesis of teichuronic acid, polyamines, polar lipids and diaminopimelic acid
      were detected. The peptidoglycan contained meso-diaminopimelic acid and the main
      polar lipid detected was phosphatidylglycerol. The major metabolic end product of
      glucose was acetic acid, which was in agreement with those of most members of the
      family. However, the profile of major cellular fatty acids (C16 : 0, C14 : 0,
      summed feature 4 and C13 : 0) and overall enzyme activity demonstrated phenotypic
      differentiation of strain BR31T from other closely related genera. Thus, based on
      distinct phenotypic, phylogenetic, genotypic and chemotaxonomic characteristics,
      strain BR31T is considered to represent a novel species of a new genus, for which
      the name Merdimonas faecis gen. nov., sp. nov. is proposed. The type strain of
      Merdimonas faecis is BR31T (=KCTC 15482T=JCM 30748T).

PMID- 28741996
TI  - Transcriptome changes associated with Tomato spotted wilt virus infection in
      various life stages of its thrips vector, Frankliniella fusca (Hinds).
AB  - Persistent propagative viruses maintain intricate interactions with their
      arthropod vectors. In this study, we investigated the transcriptome-level
      responses associated with a persistent propagative phytovirus infection in
      various life stages of its vector using an Illumina HiSeq sequencing platform.
      The pathosystem components included a Tospovirus, Tomato spotted wilt virus
      (TSWV), its insect vector, Frankliniella fusca (Hinds), and a plant host, Arachis
      hypogaea (L.). We assembled (de novo) reads from three developmental stage groups
      of virus-exposed and non-virus-exposed F. fusca into one transcriptome consisting
      of 72 366 contigs and identified 1161 differentially expressed (DE) contigs. The
      number of DE contigs was greatest in adults (female) (562) when compared with
      larvae (first and second instars) (395) and pupae (pre- and pupae) (204).
      Upregulated contigs in virus-exposed thrips had blastx annotations associated
      with intracellular transport and virus replication. Upregulated contigs were also
      assigned blastx annotations associated with immune responses, including apoptosis
      and phagocytosis. In virus-exposed larvae, Blast2GO analysis identified
      functional groups, such as multicellular development with downregulated contigs,
      while reproduction, embryo development and growth were identified with
      upregulated contigs in virus-exposed adults. This study provides insights into
      differences in transcriptome-level responses modulated by TSWV in various life
      stages of an important vector, F. fusca.

PMID- 28741997
TI  - Paracoccus hibiscisoli sp. nov., isolated from the rhizosphere of Mugunghwa
      (Hibiscus syriacus).
AB  - A Gram-reaction-negative, aerobic, non-motile, short-rod-shaped bacterium (THG
      T2.31T) was isolated from the rhizosphere of Mugunghwa (Hibiscus syriacus).
      Growth occurred at 10-35  degrees C (optimum 28  degrees C), at pH 5.0-8.0
      (optimum pH 7.0) and with 0-4.0 % NaCl (optimum 1.0 %). Based on 16S rRNA gene
      sequence analysis, the nearest phylogenetic neighbours of strain THG-T2.31T were
      identified as Paracoccus marcusii DSM 11574T (98.4 %), Paracoccus haeundaensis
      BC74171T (98.3 %), Paracoccus carotinifaciens E-396T (98.3 %), Paracoccus
      aestuarii B7T (97.3 %) and Paracoccus seriniphilus MBT-A4T (97.0 %); levels of
      similarity with the type strains of other species of the genus Paracoccus were
      lower than 97.0 %. The polar lipids were diphosphatidylglycerol,
      phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol,
      phosphatidylcholine, one unidentified aminolipid and two unidentified
      phospholipids. The major fatty acids were C16 : 0, C18 : 0, C10 : 0 3-OH, and C18
      : 1omega7c. The quinone was ubiquinone-10 (Q-10). The DNA G+C content of strain
      THG-T2.31T was 69.1 mol%. DNA-DNA hybridization values between strain THG-T2.31T
      and P. marcusii DSM 11574T, P. haeundaensis BC74171T, P. carotinifaciens E-396T,
      P. aestuarii B7T and P. seriniphilus MBT-A4T were 38.9 % (34.9 %, reciprocal
      analysis), 29.1 % (23.5 %), 28.0 % (19.7 %), 18.9 % (9.3) and 13.1 % (6.2 %). On
      the basis of the phylogenetic analysis, chemotaxonomic data, physiological
      characteristics and DNA-DNA hybridization data, strain THG-T2.31T represents a
      novel species of the genus Paracoccus, for which the name Paracoccus hibiscisoli
      sp. nov. is proposed. The type strain is THG-T2.31T (=KACC 18933T=CCTCC AB
      2016182T).

PMID- 28741998
TI  - Retention of virulence following colistin adaptation in Klebsiella pneumoniae is
      strain-dependent rather than associated with specific mutations.
AB  - This study aimed to understand the impact on virulence and fitness of mutations
      in specific genes found after adaptation of Klebsiella pneumoniae to colistin.
      Isolates with an increase in their inhibitory concentration (MIC) to colistin of
      32- to >128-fold were shown to have mutations in mgrB, phoPQ and pmrAB, all known
      regulators of pathways affecting membrane lipid content. When these strains were
      used in studies in Galleria mellonella there was no clear correlation between
      mutations in specific genes per se and loss of virulence. Strains which showed
      sequence duplication in the HAMP-domain of PmrB showed reduced virulence but
      strains with point mutations in pmrAB showed no decrease in virulence. Similarly,
      specific mutations in mgrB in individual strains showed either loss of virulence
      or no effect/increased virulence. This study suggests that the impact on
      virulence may be independent of the colistin resistance mechanism and reflects
      differences in individual strain backgrounds.

PMID- 28741999
TI  - Deakozyma yunnanensis sp. nov., a novel yeast species isolated from rotten wood.
AB  - Three strains representing a novel yeast species were isolated from rotten wood
      samples collected in Xishuangbanna Tropical Rainforest in Yunnan Province, PR
      China. Sequence analysis of the D1/D2 domains of the large subunit (LSU) rRNA
      gene and the internal transcribed spacer (ITS) regions indicated that the novel
      species represented a member of the genus Deakozyma. The novel species was
      related most closely to the type strain of Deakozyma indianensis but they
      differed by 5.8 % sequence divergence (20 substitutions and 5 gaps) in the D1/D2
      domain and by 12.2 % sequence divergence (27 substitutions and 15 gaps) in the
      ITS region. Interestingly, the novel yeast species was able to ferment glucose
      and sucrose in Durham tubes, a clear difference from its closest relative D.
      indianensis, the type species of the genus Deakozyma. The species name of
      Deakozyma yunnanensis sp. nov. is proposed to accommodate these strains, with
      NYNU 16742T (=CICC 33160T=CBS 14688T) designated the type strain. As the current
      description of the genus does not allow the inclusion of sugar fermenting
      species, the emendation of the diagnosis of the genus Deakozyma Kurtzman and
      Robnett is proposed.

PMID- 28742000
TI  - High prevalence of multidrug-resistant Escherichia coli isolates from children
      with and without diarrhoea and their susceptibility to the antibacterial activity
      of extracts/fractions of fruits native to Mexico.
AB  - PURPOSE: This paper aims to evaluate the antimicrobial resistance of Esherichia
      coli isolates from children under 5 years old, with and without diarrhoea, who
      were hospital outpatients in Culiacan, Sinaloa, Mexico. It also looks at the
      antimicrobial activity of fruit extracts against selected multidrug-resistant
      (MDR) E. coli strains. METHODOLOGY: A total of 205 E. coli isolates from stool
      samples were collected from 94 children under 5 years old who were outpatients
      from two hospitals in the city of Culiacan, Sinaloa, Mexico, during the
      autumn/winter of 2003/04; their resistance profiles to 19 commercial
      antimicrobials were investigated using the Kirby-Bauer method. The antibacterial
      activities of extracts/fractions of fruits (i.e. uvalama, Vitex mollis; ayale,
      Crescentia alata; and arrayan, Psidium sartorianum) were evaluated using the
      broth microdilution method. RESULTS: All E. coli isolates were susceptible to
      amikacin, nitrofurantoin and meropenem, and approximately 96 % were resistant to
      at least one antimicrobial, especially carbenicillin (93.2 %), cefuroxime sodium
      (53.7 %), ampicillin (40 %) and trimethoprim/sulfamethoxazole (35.1 %). Likewise,
      the frequency of MDR strains (44.9 %) was high, and no significant association
      with diarrhoea symptoms was found. Remarkably, all fruit extracts/fractions
      showed antibacterial activity against some, but not all, MDR isolates. The lowest
      minimal inhibitory concentration values were for the hexane fraction of arrayan
      (0.25 mg ml-1). CONCLUSION: A high number of antimicrobial-resistant E. coli
      (especially to beta-lactams and sulfonamides) and MDR isolates were detected in
      children under 5 years old, irrespective of diarrhoea symptoms; this is novel
      information for Culiacan, Sinaloa, Mexico. Moreover, our results showed that the
      studied fruit extracts/fractions are potential alternative or complementary
      treatments for MDR E. coli strains.

PMID- 28742002
TI  - Cdc42 activation state affects its localization and protein levels in fission
      yeast.
AB  - Rho GTPases control polarized cell growth and are well-known regulators of
      exocytic and endocytic processes. Cdc42 is an essential GTPase, conserved from
      yeast to humans, that is critical for cell polarization. Cdc42 is negatively
      regulated by the GTPase-activating proteins (GAPs) and the GDP dissociation
      inhibitors (GDIs), and positively regulated by guanine nucleotide exchange
      factors (GEFs). Cdc42 GTPase can be found in a GTP- or GDP-bound state, which
      determines the ability to bind downstream effector proteins and activate
      signalling pathways. Only GTP-bound Cdc42 is active. In this study we have
      analysed the localization of the different nucleotide-bound states of Cdc42 in
      Schizosaccharomyces pombe: the wild-type Cdc42 protein that cycles between an
      active and inactive form, the Cdc42G12V form that is permanently bound to GTP and
      the Cdc42T17N form that is constitutively inactive. Our results indicate that
      Cdc42 localizes to several membrane compartments in the cell and this
      localization is mediated by its C-terminal prenylation. Constitutively active
      Cdc42 localizes mainly to the plasma membrane and concentrates at the growing
      tips where it is considerably less dynamic than wild-type or GDP-bound Cdc42.
      Additionally we show that the activation state of Cdc42 also participates in the
      regulation of its protein levels mediated by endocytosis and by the exocyst
      complex.

PMID- 28742001
TI  - Molecular cloning of porcine Siglec-3, Siglec-5 and Siglec-10, and identification
      of Siglec-10 as an alternative receptor for porcine reproductive and respiratory
      syndrome virus (PRRSV).
AB  - In recent years, several entry mediators have been characterized for porcine
      reproductive and respiratory syndrome virus (PRRSV). Porcine sialoadhesin [pSn,
      also known as sialic acid-binding immunoglobulin-type lectin (Siglec-1)] and
      porcine CD163 (pCD163) have been identified as the most important host entry
      mediators that can fully coordinate PRRSV infection into macrophages. However,
      recent isolates have not only shown a tropism for sialoadhesin-positive cells,
      but also for sialoadhesin-negative cells. This observation might be partly
      explained by the existence of additional receptors that can support PRRSV binding
      and entry. In the search for new receptors, recently identified porcine Siglecs
      (Siglec-3, Siglec-5 and Siglec-10), members of the same family as sialoadhesin,
      were cloned and characterized. Only Siglec-10 was able to significantly improve
      PRRSV infection and production in a CD163-transfected cell line. Compared with
      sialoadhesin, Siglec-10 performed equally effectively as a receptor for PRRSV
      type 2 strain MN-184, but it was less capable of supporting infection with PRRSV
      type 1 strain LV (Lelystad virus). Siglec-10 was demonstrated to be involved in
      the endocytosis of PRRSV, confirming the important role of Siglec-10 in the entry
      process of PRRSV. In conclusion, it can be stated that PRRSV may use several
      Siglecs to enter macrophages, which may explain the strain differences in the
      pathogenesis.

PMID- 28742003
TI  - Hepatitis C virus subtype 3a was introduced in the USSR in the early 1980s.
AB  - A total of 2120 nucleotide sequences of the NS5b region of HCV subtype 3a were
      analysed, including 310 strains derived from former republics of the USSR
      (Azerbaijan, Estonia, Lithuania, Russia, Tajikistan and Uzbekistan). Among the
      viral isolates collected from former regions of the Soviet Union, 294 strains
      formed 3 sustained phylogenetic clusters, with each having a common origin.
      Phylodynamic analysis demonstrated that the most recent common ancestors of the
      current strains inside the three clusters were introduced into the USSR
      population in 1981+/-1, 1984+/-2 and 1985+/-2, respectively (the confidence
      intervals were calculated using Student's t-distribution, P<0.05). The time
      estimation obtained for HCV subtype 3a correlated well with the historical and
      epidemiological context of this period, and in particular with the start of
      widespread injection drug use in the USSR in the first half of the 1980s.

PMID- 28742004
TI  - Evolutionary changes in the capsid P2 region of Australian strains of the
      norovirus GII.Pe_GII.4.
AB  - PURPOSE: The protruding (P) 2 region of the norovirus capsid is thought to
      include hypervariable sites involved in receptor binding. This study examines the
      changes that occurred in the P2 region of GII.Pe_GII.4 norovirus in the course of
      its evolution from a precursor phase (2008-2009), to an intermediate phase (2010)
      and finally to an epidemic phase (2012-2015). METHODOLOGY: Twenty-two P2 region
      amino acid (aa) sequences (166 aa long) from all phases of the evolution of the
      virus were compared and the changes analysed.Results/key findings. Twenty sites
      in the P2 region underwent aa change and of these, 10 corresponded to previously
      proposed hypervariable sites and 10 to novel hypervariable sites. It was notable
      that aa changes at two sites, X and Y, only emerged as the epidemic phase
      progressed. 3D computer modelling of the P2 region indicated that neither X nor Y
      were in the uppermost 'crown', but further down in the 'neck' portion. The
      location of X and Y and the nature of aa change at Y suggest these sites were
      important in enhancing the structural integrity of the capsid, which in turn may
      have facilitated the longer term viability of the virus. CONCLUSION: The current
      study helps establish the validity of previously proposed hypervariable sites in
      the P2 region as well as indicating new ones. It also provides quantitative and
      qualitative data on how these sites changed over the evolutionary history of a
      particular norovirus strain.

PMID- 28742005
TI  - Nakazawaea todaengensis f.a., sp. nov., a yeast isolated from a peat swamp forest
      in Thailand.
AB  - Strain DMKU-PS11(1)T was isolated from peat in a swamp forest in Thailand. DNA
      sequence analysis showed that it belonged to a novel species that was most
      closely related to Nakazawaea laoshanensis. However, it differed from the type
      strain of N. laoshanensis (NRRL Y-63634T) by 2.3 % nucleotide substitutions in
      the D1/D2 region of the large subunit (LSU) rRNA gene, 1.0 % nucleotide
      substitutions in the small subunit (SSU) rRNA gene and 8.0 % nucleotide
      substitutions in the internal transcribed spacer (ITS) region. The phylogenetic
      analyses based on the combined sequences of the SSU and the D1/D2 region and that
      of the SSU sequences alone confirmed the placement of the novel species in the
      Nakazawaea clade and its close affinity with N. laoshanensis. Hence, the species
      Nakazawaea todaengensis f.a., sp. nov. is proposed. The type strain is DMKU
      PS11(1)T (=CBS 14555T=TBRC 6559T). The MycoBank number for Nakazawaea
      todaengensis f.a., sp. nov. is MB 819513.

PMID- 28742006
TI  - Flavobacterium soyangense sp. nov., a psychrotolerant bacterium, isolated from an
      oligotrophic freshwater lake.
AB  - A bacterial strain, designated IMCC26223T, was isolated from an oligotrophic
      freshwater lake, Lake Soyang, Korea. Cells of strain IMCC26223T were Gram
      staining negative, strictly aerobic, non-motile and short-rod-shaped. Growth
      occurred at pH 6-8 (optimum, pH 7.0), at 4-25  degrees C (optimum, 15  degrees C)
      and with 0-0.5 % (w/v) NaCl (optimum, 0 %). Phylogenetic analyses based on 16S
      rRNA gene sequences showed that strain IMCC26223T was identified as a member of
      the genus Flavobacterium and most closely related to Flavobacterium fluvii H7T
      (97.6 %), Flavobacterium segetis AT1048T (97.5 %) and Flavobacterium weaverense
      AT1042T (97.2 %). DNA-DNA relatedness between strain IMCC26223T and F. fluvii H7T
      was 41.5-51.7 % in the reciprocal hybridization. Strain IMCC26223T contained MK-6
      as the major respiratory quinone. The major cellular fatty acids consisted of C16
      : 0, iso-C15 : 0, anteiso-C15 : 0 and summed feature 3 (C16 : 1omega6c and/or C16
      : 1omega7c), and the polar lipids were phosphatidylethanolamine, an unidentified
      aminolipid and two unidentified lipids. The DNA G+C content of strain IMCC26223T
      was 34.5 mol%. On the basis of 16S rRNA gene phylogeny and phenotypic
      characterization, strain IMCC26223T represents a novel species of the genus
      Flavobacterium, for which the name Flavobacterium soyangense sp. nov., is
      proposed. The type strain is IMCC26223T (=KCTC 52245T=JCM 31384T).

PMID- 28742007
TI  - Galliscardovia ingluviei gen. nov., sp. nov., a thermophilic bacterium of the
      family Bifidobacteriaceae isolated from the crop of a laying hen (Gallus gallus
      f. domestica).
AB  - Bacteria with potential probiotic applications are not yet sufficiently explored,
      even for animals with economic importance. Therefore, we decided to isolate and
      identify representatives of the family Bifidobacteriaceae, which inhabit the crop
      of laying hens. During the study, a fructose-6-phosphate phosphoketolase-positive
      strain, RP51T, with a regular/slightly irregular and sometimes an S-shaped
      slightly curved rod-like shape, was isolated from the crop of a 13 -month-old
      Hisex Brown hybrid laying hen. The best growth of the Gram-stain-positive
      bacterium, which was isolated using Bifidobacterium-selective mTPY agar, was
      found out to be under strictly anaerobic conditions, however an ability to grow
      under microaerophilic and aerobic conditions was also observed. Sequencing of the
      almost complete 16S rRNA gene (1444 bp) showed Alloscardovia omnicolens CCUG
      31649T and Bombiscardovia coagulans BLAPIII/AGVT to be the most closely related
      species with similarities of 93.4 and 93.1 %, respectively. Lower sequence
      similarities were determined with other scardovial genera and other
      representatives of the genus Bifidobacterium. Taxonomic relationships with A.
      omnicolens and other members of the family Bifidobacteriaceaewere also
      demonstrated, based on the sequences of dnaK, fusA, hsp60 and rplB gene
      fragments. Low sequence similarities of phylogenetic markers to related
      scardovial genera and bifidobacteria along with unique features of the bacterial
      strain investigated within the family Bifidobacteriaceae(including the lowest DNA
      G+C value (44.3 mol%), a unique spectrum of cellular fatty acids and polar
      lipids, cellular morphology, the wide temperature range for growth (15-49 
      degrees C) and habitat) clearly indicate that strain RP51T is a representative of
      a novel genus within the family Bifidobacteriaceae for which the name
      Galliscardovia ingluviei gen. nov., sp. nov. (RP51T=DSM 100235T=LMG 28778T=CCM
      8606T) is proposed.

PMID- 28742008
TI  - Development of a CRISPR/Cas9-mediated gene-editing tool in Streptomyces rimosus.
AB  - Clustered regularly interspaced short palindromic repeats, associated proteins
      (CRISPR/Cas), has been developed into a powerful, targeted genome-editing tool in
      a wide variety of species. Here, we report an extensive investigation of the type
      II CRISPR/Cas9 system for targeted gene editing in Streptomyces rimosus. S.
      rimosus is used in the production of the antibiotic oxytetracycline, and its
      genome differs greatly from other species of the genus Streptomyces in the
      conserved chromosome terminal and core regions, which is of major production and
      scientific research value. The genes zwf2 and devB were chosen as target genes,
      and were edited separately via single-site mutations, double-site mutations and
      gene fragment disruptions. The single-site mutation guided by sgRNA-1 or sgRNA-2,
      respectively, involved GG changing to CA, GC changing to AT, and GG changing to
      CC. The double-site mutations guided by sgRNA-1 and sgRNA-2 included deletions
      and/or point mutations. Consistently, all mutations occurred in the gRNA sequence
      regions. Deletion mutations were characterized by the absence of eight bases,
      including three bases upstream of the PAM (protospacer adjacent motif) sequence,
      the PAM sequence itself and two bases downstream of the PAM sequence. A mutant
      (zwf2-devB-) with a high yield of oxytetracycline was successfully obtained,
      whose oxytetracycline level was increased by 36.8 % compared to the original
      strain. These results confirm that CRISPR/Cas9 can successfully serve as a useful
      targeted genome editing system in S. rimosus.

PMID- 28742009
TI  - Megasphaera hexanoica sp. nov., a medium-chain carboxylic acid-producing
      bacterium isolated from a cow rumen.
AB  - Strain MHT, a strictly anaerobic, Gram-stain-negative, non-spore-forming,
      spherical coccus or coccoid-shaped microorganism, was isolated from a cow rumen
      during a screen for hexanoic acid-producing bacteria. The microorganism grew at
      30-40  degrees C and pH 5.5-7.5 and exhibited production of various short- and
      medium-chain carboxylic acids (acetic acid, butyric acid, pentanoic acid,
      isobutyric acid, isovaleric acid, hexanoic acid, heptanoic acid and octanoic
      acid), as well as H2 and CO2 as biogas. Phylogenetic analysis based on 16S rRNA
      gene sequencing demonstrated that MHT represents a member of the genus
      Megasphaera, with the closest relatives being Megapsphaera indica NMBHI-10T (94.1
      % 16S rRNA sequence similarity), Megasphaera elsdenii DSM 20460T (93.8 %) and
      Megasphaera paucivorans DSM 16981T (93.8 %). The major cellular fatty acids
      produced by MHT included C12 : 0, C16 : 0, C18 : 1cis 9, and C18 : 0, and the DNA
      G+C content of the MHT genome is 51.8 mol%. Together, the distinctive phenotypic
      and phylogenetic characteristics of MHT indicate that this microorganism
      represents a novel species of the genus Megasphaera, for which the name
      Megasphaera hexanoica sp. nov. is herein proposed. The type strain of this
      species is MHT (=KCCM 43214T=JCM 31403T).

PMID- 28742010
TI  - Bacterial communities in the small intestine respond differently to those in the
      caecum and colon in mice fed low- and high-fat diets.
AB  - Bacterial communities in the mouse caecum and faeces are known to be altered by
      changes in dietary fat. The microbiota of the mouse small intestine, by contrast,
      has not been extensively profiled and it is unclear whether small intestinal
      bacterial communities shift with dietary fat levels. We compared the microbiota
      in the small intestine, caecum and colon in mice fed a low-fat (LF) or high-fat
      (HF) diet using 16S rRNA gene sequencing. The relative abundance of major phyla
      in the small intestine, Bacteriodetes, Firmicutes and Proteobacteria, was similar
      to that in the caecum and colon; the relative abundance of Verrucomicrobia was
      significantly reduced in the small intestine compared to the large intestine.
      Several genera were uniquely detected in the small intestine and included the
      aerotolerant anaerobe, Lactobacillus spp. The most abundant genera in the small
      intestine were accounted for by anaerobic bacteria and were identical to those
      identified in the large intestine. An HF diet was associated with significant
      weight gain and adiposity and with changes in the bacterial communities
      throughout the intestine, with changes in the small intestine differing from
      those in the caecum and colon. Prominent Gram-negative bacteria including genera
      of the phylum Bacteroidetes and a genus of Proteobacteria significantly changed
      in the large intestine. The mechanistic links between these changes and the
      development of obesity, perhaps involving metabolic endotoxemia, remain to be
      determined.

PMID- 28742011
TI  - Toward late career transitioning: a proposal for academic surgeons.
AB  - SUMMARY: In the absence of a defined retirement age, academic surgeons need to
      develop plans for transition as they approach the end of their academic surgical
      careers. The development of a plan for late career transition represents an
      opportunity for departments of surgery across Canada to initiate a constructive
      process in cooperation with the key stakeholders in the hospital or institution.
      The goal of the process is to develop an individual plan for each faculty member
      that is agreeable to the academic surgeon; informs the surgical leadership; and
      allows the late career surgeon, the hospital, the division and the department to
      make plans for the future. In this commentary, the literature on the science of
      aging is reviewed as it pertains to surgeons, and guidelines for late career
      transition planning are shared. It is hoped that these guidelines will be of some
      value to academic programs and surgeons across the country as late career
      transition models are developed and adopted.

PMID- 28742012
TI  - The usefulness and costs of routine contrast studies after laparoscopic sleeve
      gastrectomy for detecting staple line leaks.
AB  - BACKGROUND: Although laparoscopic sleeve gastrectomy (LSG) has been shown to be a
      safe and effective treatment for severe obesity (body mass index >= 35), staple
      line leaks remain a major complication and account for a substantial portion of
      the procedure's morbidity and mortality. Many centres performing LSG routinely
      obtain contrast studies on postoperative day 1 for early detection of staple line
      leaks. We examined the usefulness of Gastrografin swallow as an early detection
      test for staple line leaks on postoperative day 1 after LSG as well as the
      associated costs. METHODS: We conducted a retrospective review of a prospectively
      collected database that included 200 patients who underwent LSG for severe
      obesity between 2011 and 2014. Primary outcome measures were the incidence of
      staple line leaks and the results of Gastrografin swallow tests. We obtained
      imaging costs from appropriate hospital departments. RESULTS: Gastrografin
      swallow was obtained on postoperative day 1 for all 200 patients who underwent
      LSG. Three patients (1.5%) were found to have staple line leaks. Gastrograffin
      swallows yielded 1 true positive result and 2 false negatives. The false
      negatives were subsequently diagnosed on computed tomography (CT) scan. The
      sensitivity of Gastrografin swallow in this study was 33%. For 200 patients, the
      total direct cost of the Gastrografin swallows was $35 000. CONCLUSION: The use
      of routine upper gastrointestinal contrast studies for early detection of staple
      line leaks has low sensitivity and is costly. We recommend selective use of CT
      instead.

PMID- 28742013
TI  - First Canadian experience with donation after cardiac death simultaneous pancreas
      and kidney transplants.
AB  - BACKGROUND: Compared with neurologic determination of death (NDD) donor organs,
      donation after cardiac death (DCD) donor organs have traditionally been
      considered of inferior quality owing to warm ischemia experienced during
      procurement. We present, to our knowledge, the first analysis of simultaneous
      pancreas and kidney (SPK) transplants using DCD donor organs in Canada. METHODS:
      We carried out a retrospective cohort study of SPK transplants from 13 DCD and 68
      NDD donors performed between October 2008 and July 2016. In all patients
      immunosuppression was induced with thymoglobulin and continued with tacrolimus,
      mycophenolate mofetil and prednisone maintenance therapy. RESULTS: Donor and
      recipient characteristics of DCD and NDD groups were similar with respect to age,
      sex, body mass index, kidney and pancreas cold ischemia times, and donor terminal
      creatinine. Mean DCD graft warm ischemia time was 0.5 (range 0.4-0.7) hours.
      Median follow-up was 2.2 (range 0.1-6.7) years and 2.7 (range 0.3-6.3) years for
      the DCD and NDD groups, respectively. The DCD and NDD groups were similar with
      regards to recipient percent panel reactive antibody and presence of human
      leukocyte antigen antibodies. The groups also received similar total doses of
      thymoglobulin. In total 38% of patients in the DCD group experienced renal
      delayed graft function (DGF) compared with 10% in the NDD group (p = 0.027).
      There were 7 cases of pancreas graft thrombosis requiring relaparotomy in the NDD
      group compared with none in the DCD group. No patients from either group required
      insulin at any time after transplant. Although the estimated glomerular
      filtration rate (eGFR) was lower in the DCD than the NDD group on postoperative
      days 7 and 14 (p = 0.025), no difference was noted on day 30 or through 4 years
      after transplant. No differences were seen between the groups with respect to
      amylase, lipase, or glycosated hemoglobin (HbA1c) up to 4 years after transplant,
      or in kidney, pancreas, or patient survival at any time after transplant.
      CONCLUSION: Our results show that, apart from a higher renal DGF rate, SPK
      transplants with DCD donor organs have comparable outcomes to standard
      transplants with NDD donor organs.

PMID- 28742014
TI  - Results and limitations of outpatient and overnight stay laminectomies for lumbar
      spinal stenosis.
AB  - BACKGROUND: At our centre, laminectomies have been traditionally performed as
      inpatient surgery. A gradual change in practice occurred between 2010 and 2013 to
      try to do these procedures as outpatient or overnight stay surgery. METHODS: We
      conducted a retrospective cohort study of consecutive patients having
      laminectomies over 2 18-month periods: before the change in practice and after
      full implementation of the outpatient/overnight stay protocol. We collected
      information on patient characteristics (age, sex, American Society of
      Anesthesiologists [ASA] classification, home address, number of laminectomy
      levels, estimated blood loss) and patient outcome (complications, hospital length
      of stay, 30-day readmissions). RESULTS: We found no significant difference in
      age, sex, ASA classification, number of laminectomy levels, or estimated blood
      loss between the 2 cohorts. There was a change in the number of outpatient (from
      0 to 25) and overnight stay laminectomies (from 0 to 13). There was an increase
      in total (inpatient, overnight stay and outpatient) laminectomies from 41 to 82,
      and an increase in patients from out of our region from 15% to 32%. There was 1
      readmission within 30 days that occurred in the first cohort. CONCLUSION: We
      found that outpatient and overnight stay laminectomies can be done safely, with
      no patients requiring postoperative admission to hospital or readmissions within
      30 days. They can be done in patients from out of town who need to travel home
      postoperatively. It is possible to safely reduce the level of resources used for
      spine surgery by carrying out laminectomies as outpatient or overnight stay
      surgery in select patients.

PMID- 28742015
TI  - Topical tranexamic acid reduces transfusion rates in simultaneous bilateral total
      knee arthroplasty: a retrospective case series.
AB  - BACKGROUND: Topical tranexamic acid (TA) has been reported to be effective in
      reducing postoperative bleeding and transfusions after total knee arthroplasty
      (TKA). The main objective of this study was to retrospectively assess the
      effectiveness and safety of topical TA administration in patients undergoing
      simultaneous bilateral TKA. METHODS: We conducted a retrospective chart review of
      consecutive cohorts of patients undergoing simultaneous bilateral TKA. We
      compared the patients who received TA with patients from a similar time frame who
      did not receive TA. For those who received TA, a topical concentration of 2 g per
      30 mL of normal saline was used in each knee. Preoperative and postoperative
      hemoglobin, transfusions, length of stay (LOS) and postoperative complications
      were recorded for each patient until discharge. Outcome measures were analyzed
      using independent t test, chi2 test and logistic regression. RESULTS: We included
      49 patients in our analysis: 25 who received TA and 24 who did not. There were no
      statistical differences in demographics between the groups. The rate of
      transfusion in the TA group was 4% compared with 67% in the non-TA group (p <
      0.001). The net hemoglobin loss in the TA group was 4.1 g/dL versus 6.2 g/dL in
      the non-TA group (p < 0.001). The use of TA was found to be associated with a
      greater than 99% reduced risk of receiving a transfusion (odds ratio 0.003, 95%
      confidence interval < 0.001-0.072, p < 0.001). There were no thromboembolic
      events in patients who received TA, and there was 1 pulmonary embolus in the non
      TA group. Postoperative LOS was significantly reduced in the TA group (mean
      difference 1.1 d, p = 0.005). CONCLUSION: Topical administration of TA in
      patients undergoing simultaneous bilateral TKA significantly reduced
      transfusions, blood loss and postoperative LOS, with no increased risk of
      thromboembolic events.

PMID- 28742016
TI  - Intraoperative ultrasonography of the biliary tract using saline as a contrast
      agent: a fast and accurate technique to identify complex biliary anatomy.
AB  - BACKGROUND: Intraoperative assessment of biliary tract anatomy is relevant for a
      number of benign and malignant hepatobiliary diseases. During biliary
      reconstruction, drainage of all relevant bile ducts is imperative to prevent
      atrophy of undrained segment, cholangitis and secondary biliary cirrhosis.
      Intraoperative cholangiography, though widely used for intraoperative imaging of
      the biliary tract, involves heavy equipment use, radiation risk and has a limited
      role in the evaluation of isolated segmental bile ducts. METHODS: We evaluated
      the use of a novel technique of intraoperative ultrasonography of the biliary
      tract using normal saline as a contrast agent. It involves injecting saline in
      any part of the biliary system while performing real-time intraoperative 2
      dimensional ultrasonography. RESULTS: This procedure was carried out in
      intraoperative situations to delineate complex biliary anatomy involving
      segmental bile ducts. Excellent image quality was obtained in the form of
      opacification and demarcation of the liver segment to which the duct belongs. The
      flow of saline microbubbles was clearly visible on real-time ultrasound images,
      leading to accurate identification of the duct. CONCLUSION: Intraoperative
      ultrasonography with saline as a contrast agent can accurately identify small
      isolated segmental bile ducts and help in surgery of the biliary tract. It is a
      simple and inexpensive technique that can be performed with minimal resources.

PMID- 28742017
TI  - Nanoparticles Help Break Up Plaque, Prevent Cavities.

PMID- 28742018
TI  - Dynamic structure of locomotor behavior in walking fruit flies.
AB  - The function of the brain is unlikely to be understood without an accurate
      description of its output, yet the nature of movement elements and their
      organization remains an open problem. Here, movement elements are identified from
      dynamics of walking in flies, using unbiased criteria. On one time scale,
      dynamics of walking are consistent over hundreds of milliseconds, allowing
      elementary features to be defined. Over longer periods, walking is well described
      by a stochastic process composed of these elementary features, and a generative
      model of this process reproduces individual behavior sequences accurately over
      seconds or longer. Within elementary features, velocities diverge, suggesting
      that dynamical stability of movement elements is a weak behavioral constraint.
      Rather, long-term instability can be limited by the finite memory between these
      elementary features. This structure suggests how complex dynamics may arise in
      biological systems from elements whose combination need not be tuned for dynamic
      stability.

PMID- 28742019
TI  - High lumenal chloride in the lysosome is critical for lysosome function.
AB  - Lysosomes are organelles responsible for the breakdown and recycling of cellular
      machinery. Dysfunctional lysosomes give rise to lysosomal storage disorders as
      well as common neurodegenerative diseases. Here, we use a DNA-based, fluorescent
      chloride reporter to measure lysosomal chloride in Caenorhabditis elegans as well
      as murine and human cell culture models of lysosomal diseases. We find that the
      lysosome is highly enriched in chloride, and that chloride reduction correlates
      directly with a loss in the degradative function of the lysosome. In nematodes
      and mammalian cell culture models of diverse lysosomal disorders, where
      previously only lysosomal pH dysregulation has been described, massive reduction
      of lumenal chloride is observed that is ~103 fold greater than the accompanying
      pH change. Reducing chloride within the lysosome impacts Ca2+ release from the
      lysosome and impedes the activity of specific lysosomal enzymes indicating a
      broader role for chloride in lysosomal function.

PMID- 28742020
TI  - Symmetry broken and rebroken during the ATP hydrolysis cycle of the mitochondrial
      Hsp90 TRAP1.
AB  - Hsp90 is a homodimeric ATP-dependent molecular chaperone that remodels its
      substrate 'client' proteins, facilitating their folding and activating them for
      biological function. Despite decades of research, the mechanism connecting ATP
      hydrolysis and chaperone function remains elusive. Particularly puzzling has been
      the apparent lack of cooperativity in hydrolysis of the ATP in each protomer. A
      crystal structure of the mitochondrial Hsp90, TRAP1, revealed that the
      catalytically active state is closed in a highly strained asymmetric
      conformation. This asymmetry, unobserved in other Hsp90 homologs, is due to
      buckling of one of the protomers and is most pronounced at the broadly conserved
      client-binding region. Here, we show that rather than being cooperative or
      independent, ATP hydrolysis on the two protomers is sequential and deterministic.
      Moreover, dimer asymmetry sets up differential hydrolysis rates for each
      protomer, such that the buckled conformation favors ATP hydrolysis. Remarkably,
      after the first hydrolysis, the dimer undergoes a flip in the asymmetry while
      remaining in a closed state for the second hydrolysis. From these results, we
      propose a model where direct coupling of ATP hydrolysis and conformational
      flipping rearranges client-binding sites, providing a paradigm of how energy from
      ATP hydrolysis can be used for client remodeling.

PMID- 28742021
TI  - Resolving the prevalence of somatic transposition in Drosophila.
AB  - Somatic transposition in mammals and insects could increase cellular diversity
      and neural mobilization has been implicated in age-dependent decline. To
      understand the impact of transposition in somatic cells it is essential to
      reliably measure the frequency and map locations of new insertions. Here we
      identified thousands of putative somatic transposon insertions in neurons from
      individual Drosophila melanogaster using whole-genome sequencing. However, the
      number of de novo insertions did not correlate with transposon expression or fly
      age. Analysing our data with exons as 'immobile genetic elements' revealed a
      similar frequency of unexpected exon translocations. A new sequencing strategy
      that recovers transposon: chromosome junction information revealed most putative
      de novo transposon and exon insertions likely result from unavoidable chimeric
      artefacts. Reanalysis of other published data suggests similar artefacts are
      often mistaken for genuine somatic transposition. We conclude that somatic
      transposition is less prevalent in Drosophila than previously envisaged.

PMID- 28742022
TI  - Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins.
AB  - Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought
      to be continuous with ER throughout the neuron; the mechanisms that form this
      axonal network are unknown. Mutations affecting reticulon or REEP proteins, with
      intramembrane hairpin domains that model ER membranes, cause an axon degenerative
      disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have
      a dynamic axonal ER network, which these proteins help to model. Loss of HSP
      hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor
      axons, and occasional discontinuities in axonal ER. Ultrastructural analysis
      reveals an extensive ER network in axons, which shows larger and fewer tubules in
      larvae that lack reticulon and REEP proteins, consistent with loss of membrane
      curvature. Therefore HSP hairpin-containing proteins are required for shaping and
      continuity of axonal ER, thus suggesting roles for ER modeling in axon
      maintenance and function.

PMID- 28742023
TI  - Genome-wide identification of lineage and locus specific variation associated
      with pneumococcal carriage duration.
AB  - Streptococcus pneumoniae is a leading cause of invasive disease in infants,
      especially in low-income settings. Asymptomatic carriage in the nasopharynx is a
      prerequisite for disease, but variability in its duration is currently only
      understood at the serotype level. Here we developed a model to calculate the
      duration of carriage episodes from longitudinal swab data, and combined these
      results with whole genome sequence data. We estimated that pneumococcal genomic
      variation accounted for 63% of the phenotype variation, whereas the host traits
      considered here (age and previous carriage) accounted for less than 5%. We
      further partitioned this heritability into both lineage and locus effects, and
      quantified the amount attributable to the largest sources of variation in
      carriage duration: serotype (17%), drug-resistance (9%) and other significant
      locus effects (7%). A pan-genome-wide association study identified prophage
      sequences as being associated with decreased carriage duration independent of
      serotype, potentially by disruption of the competence mechanism. These findings
      support theoretical models of pneumococcal competition and antibiotic resistance.

PMID- 28742024
TI  - Elastic force restricts growth of the murine utricle.
AB  - Dysfunctions of hearing and balance are often irreversible in mammals owing to
      the inability of cells in the inner ear to proliferate and replace lost sensory
      receptors. To determine the molecular basis of this deficiency we have
      investigated the dynamics of growth and cellular proliferation in a murine
      vestibular organ, the utricle. Based on this analysis, we have created a
      theoretical model that captures the key features of the organ's morphogenesis.
      Our experimental data and model demonstrate that an elastic force opposes growth
      of the utricular sensory epithelium during development, confines cellular
      proliferation to the organ's periphery, and eventually arrests its growth. We
      find that an increase in cellular density and the subsequent degradation of the
      transcriptional cofactor Yap underlie this process. A reduction in mechanical
      constraints results in accumulation and nuclear translocation of Yap, which
      triggers proliferation and restores the utricle's growth; interfering with Yap's
      activity reverses this effect.

PMID- 28742025
TI  - Structure and reconstitution of yeast Mpp6-nuclear exosome complexes reveals that
      Mpp6 stimulates RNA decay and recruits the Mtr4 helicase.
AB  - Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that
      are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA
      helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47
      stabilizes the exoribonuclease Rrp6 and recruits Mtr4, but it is less clear if
      these cofactors work together. Using biochemistry with Saccharomyces cerevisiae
      proteins, we show that Rrp47 and Mpp6 stimulate exosome-mediated RNA decay,
      albeit with unique dependencies on elements within the nuclear exosome. Mpp6
      exosomes can recruit Mtr4, while Mpp6 and Rrp47 each contribute to Mtr4-dependent
      RNA decay, with maximal Mtr4-dependent decay observed with both cofactors. The
      3.3 A structure of a twelve-subunit nuclear Mpp6 exosome bound to RNA shows the
      central region of Mpp6 bound to the exosome core, positioning its Mtr4
      recruitment domain next to Rrp6 and the exosome central channel. Genetic analysis
      reveals interactions that are largely consistent with our model.

PMID- 28742027
TI  - A Regularized Deep Learning Approach for Clinical Risk Prediction of Acute
      Coronary Syndrome Using Electronic Health Records.
AB  - OBJECTIVE: Acute coronary syndrome (ACS), as a common and severe cardiovascular
      disease, is a leading cause of death and the principal cause of serious long-term
      disability globally. Clinical risk prediction of ACS is important for early
      intervention and treatment. Existing ACS risk scoring models are based mainly on
      a small set of hand-picked risk factors and often dichotomize predictive
      variables to simplify the score calculation. METHODS: This study develops a
      regularized stacked denoising autoencoder (SDAE) model to stratify clinical risks
      of ACS patients from a large volume of electronic health records (EHR). To
      capture characteristics of patients at similar risk levels, and preserve the
      discriminating information across different risk levels, two constraints are
      added on SDAE to make the reconstructed feature representations contain more risk
      information of patients, which contribute to a better clinical risk prediction
      result. RESULTS: We validate our approach on a real clinical dataset consisting
      of 3464 ACS patient samples. The performance of our approach for predicting ACS
      risk remains robust and reaches 0.868 and 0.73 in terms of both AUC and accuracy,
      respectively. CONCLUSIONS: The obtained results show that the proposed approach
      achieves a competitive performance compared to state-of-the-art models in dealing
      with the clinical risk prediction problem. In addition, our approach can extract
      informative risk factors of ACS via a reconstructive learning strategy. Some of
      these extracted risk factors are not only consistent with existing medical domain
      knowledge, but also contain suggestive hypotheses that could be validated by
      further investigations in the medical domain.

PMID- 28742026
TI  - AIRE is a critical spindle-associated protein in embryonic stem cells.
AB  - Embryonic stem (ES) cells go though embryo-like cell cycles regulated by
      specialized molecular mechanisms. However, it is not known whether there are ES
      cell-specific mechanisms regulating mitotic fidelity. Here we showed that
      Autoimmune Regulator (Aire), a transcription coordinator involved in immune
      tolerance processes, is a critical spindle-associated protein in mouse ES(mES)
      cells. BioID analysis showed that AIRE associates with spindle-associated
      proteins in mES cells. Loss of function analysis revealed that Aire was important
      for centrosome number regulation and spindle pole integrity specifically in mES
      cells. We also identified the c-terminal LESLL motif as a critical motif for
      AIRE's mitotic function. Combined maternal and zygotic knockout further revealed
      Aire's critical functions for spindle assembly in preimplantation embryos. These
      results uncovered a previously unappreciated function for Aire and provide new
      insights into the biology of stem cell proliferation and potential new angles to
      understand fertility defects in humans carrying Aire mutations.

PMID- 28742028
TI  - Semantic Object Segmentation in Tagged Videos via Detection.
AB  - Semantic object segmentation (SOS) is a challenging task in computer vision that
      aims to detect and segment all pixels of the objects within predefined semantic
      categories. In image-based SOS, many supervised models have been proposed and
      achieved impressive performances due to the rapid advances of well-annotated
      training images and machine learning theories. However, in video-based SOS it is
      often difficult to directly train a supervised model since most videos are weakly
      annotated by tags. To handle such tagged videos, this paper proposes a novel
      approach that adopts a segmentation-by-detection framework. In this framework,
      object detection and segment proposals are first generated using the models pre
      trained on still images, which provide useful cues to roughly localize the
      semantic objects. Based on these proposals, we propose an efficient algorithm to
      initialize object tracks by solving a joint assignment problem. As such tracks
      provide rough spatiotemporal configurations of the semantic objects, a voting
      based refinement algorithm is further proposed to improve their spatiotemporal
      consistency. Extensive experiments demonstrate that the proposed framework can
      robustly and effectively segment semantic objects in tagged videos, even when the
      image-based object detectors provide inaccurate proposals. On various public
      benchmarks, the proposed approach obtains substantial improvements over the state
      of-the-arts.

PMID- 28742029
TI  - Collocation for Diffeomorphic Deformations in Medical Image Registration.
AB  - Diffeomorphic deformation is a popular choice in medical image registration. A
      fundamental property of diffeomorphisms is invertibility, implying that once the
      relation between two points A to B is found, then the relation B to A is given
      per definition. Consistency is a measure of a numerical algorithm's ability to
      mimic this invertibility, and achieving consistency has proven to be a challenge
      for many state-of-the-art algorithms. We present CDD (Collocation for
      Diffeomorphic Deformations), a numerical solution to diffeomorphic image
      registration, which solves for the Stationary Velocity Field (SVF) using an
      implicit A-stable collocation method. CDD guarantees the preservation of the
      diffeomorphic properties at all discrete points and is thereby consistent to
      machine precision. We compared CDD's collocation method with the following
      standard methods: Scaling and Squaring, Forward Euler, and Runge-Kutta 4, and
      found that CDD is up to 9 orders of magnitude more consistent. Finally, we
      evaluated CDD on a number of standard bench-mark data sets and compared the
      results with current state-of-the-art methods: SPM-DARTEL, Diffeomorphic Demons
      and SyN. We found that CDD outperforms state-of-the-art methods in consistency
      and delivers comparable or superior registration precision.

PMID- 28742030
TI  - Maximum Persistency via Iterative Relaxed Inference in Graphical Models.
AB  - We consider the NP-hard problem of MAP-inference for undirected discrete
      graphical models. We propose a polynomial time and practically efficient
      algorithm for finding a part of its optimal solution. Specifically, our algorithm
      marks some labels of the considered graphical model either as (i) optimal,
      meaning that they belong to all optimal solutions of the inference problem; (ii)
      non-optimal if they provably do not belong to any solution. With access to an
      exact solver of a linear programming relaxation to the MAP-inference problem, our
      algorithm marks the maximal possible (in a specified sense) number of labels. We
      also present a version of the algorithm, which has access to a suboptimal dual
      solver only and still can ensure the (non-)optimality for the marked labels,
      although the overall number of the marked labels may decrease. We propose an
      efficient implementation, which runs in time comparable to a single run of a
      suboptimal dual solver. Our method is well-scalable and shows state-of-the-art
      results on computational benchmarks from machine learning and computer vision.

PMID- 28742031
TI  - Patient-Specific Left Ventricular Flow Simulations From Transthoracic
      Echocardiography: Robustness Evaluation and Validation Against Ultrasound Doppler
      and Magnetic Resonance Imaging.
AB  - The combination of medical imaging with computational fluid dynamics (CFD) has
      enabled the study of 3-D blood flow on a patient-specific level. However, with
      models based on gated high-resolution data, the study of transient flows, and any
      model implementation into routine cardiac care, is challenging. This paper
      presents a novel pathway for patient-specific CFD modelling of the left ventricle
      (LV), using 4-D transthoracic echocardiography (TTE) as input modality. To
      evaluate the clinical usability, two sub-studies were performed. First, a
      robustness evaluation was performed, where repeated models with alternating input
      variables were generated for six subjects and changes in simulated output
      quantified. Second, a validation study was carried out, where the pathway
      accuracy was evaluated against pulsed-wave Doppler (100 subjects), and 2-D
      through-plane phase-contrast magnetic resonance imaging measurements over seven
      intraventricular planes (6 subjects). The robustness evaluation indicated a model
      deviation of <12%, with highest regional and temporal deviations at apical
      segments and at peak systole, respectively. The validation study showed an error
      of <11% (velocities <10 cm/s) for all subjects, with no significant regional or
      temporal differences observed. With the patient-specific pathway shown to provide
      robust output with high accuracy, and with the pathway dependent only on 4-D TTE,
      the method has a high potential to be used within future clinical studies on 3-D
      intraventricular flow patterns. To this, future model developments in the form of
      e.g., anatomically accurate LV valves may further enhance the clinical value of
      the simulations.

PMID- 28742032
TI  - Architecture of an Ultrasound System for Continuous Real-Time High Frame Rate
      Imaging.
AB  - High frame rate (HFR) imaging methods based on the transmission of defocused or
      plane waves rather than focused beams are increasingly popular. However, the
      production of HFR images poses severe requirements both in the transmission and
      the reception sections of ultrasound scanners. In particular, major technical
      difficulties arise if the images must be continuously produced in real-time,
      i.e., without any acquisition interruption nor loss of data. This paper presents
      the implementation of the real-time HFR-compounded imaging application in the ULA
      OP 256 research platform. The beamformer sustains an average output sample rate
      of 470 MSPS. This allows continuously producing coherently compounded images,
      each of 64 lines by 1280 depths (here corresponding to 15.7 mm width and 45 mm
      depth, respectively), at frame rates up to 5.3 kHz. Imaging tests addressed to
      evaluate the achievable speed and quality performance were conducted on phantom.
      Results obtained by real-time compounding frames obtained with different numbers
      of steering angles between +7.5 degrees  and -7.5 degrees  are presented.

PMID- 28742034
TI  - Comments and Corrections to "An Efficient Adaptive Binary Arithmetic Coder Based
      on Logarithmic Domain" [Nov 15 4225-4239].
AB  - This correspondence is to address the corrections to the published paper titled
      "An efficient adaptive binary arithmetic coder based on logarithmic domain".

PMID- 28742033
TI  - The Impact of Model-Based Clutter Suppression on Cluttered, Aberrated Wavefronts.
AB  - Recent studies reveal that both phase aberration and reverberation play a major
      role in degrading ultrasound image quality. We previously developed an algorithm
      for suppressing clutter, but we have not yet tested it in the context of
      aberrated wavefronts. In this paper, we evaluate our previously reported
      algorithm, called aperture domain model image reconstruction (ADMIRE), in the
      presence of phase aberration and in the presence of multipath scattering and
      phase aberration. We use simulations to investigate phase aberration corruption
      and correction in the presence of reverberation. As part of this paper, we
      observed that ADMIRE leads to suppressed levels of aberration. In order to
      accurately characterize aberrated signals of interest, we introduced an adaptive
      component to ADMIRE to account for aberration, referred to as adaptive ADMIRE. We
      then use ADMIRE, adaptive ADMIRE, and conventional filtering methods to
      characterize aberration profiles on in vivo liver data. These in vivo results
      suggest that adaptive ADMIRE could be used to better characterize a wider range
      of aberrated wavefronts. The aberration profiles' full-width at half-maximum of
      ADMIRE, adaptive ADMIRE, and postfiltered data with 0.4- mm-1 spatial cutoff
      frequency are 4.0 +/- 0.28 mm, 2.8 +/- 1.3 mm, and 2.8 +/- 0.57 mm, respectively,
      while the average root-mean square values in the same order are 16 +/- 5.4 ns, 20
      +/- 6.3 ns, and 19 +/- 3.9 ns, respectively. Finally, because ADMIRE suppresses
      aberration, we perform a limited evaluation of image quality using simulations
      and in vivo data to determine how ADMIRE and adaptive ADMIRE perform with and
      without aberration correction.

PMID- 28742035
TI  - Fast Low-Rank Shared Dictionary Learning for Image Classification.
AB  - Despite the fact that different objects possess distinct class-specific features,
      they also usually share common patterns. This observation has been exploited
      partially in a recently proposed dictionary learning framework by separating the
      particularity and the commonality (COPAR). Inspired by this, we propose a novel
      method to explicitly and simultaneously learn a set of common patterns as well as
      class-specific features for classification with more intuitive constraints. Our
      dictionary learning framework is hence characterized by both a shared dictionary
      and particular (class-specific) dictionaries. For the shared dictionary, we
      enforce a low-rank constraint, i.e., claim that its spanning subspace should have
      low dimension and the coefficients corresponding to this dictionary should be
      similar. For the particular dictionaries, we impose on them the well-known
      constraints stated in the Fisher discrimination dictionary learning (FDDL).
      Furthermore, we develop new fast and accurate algorithms to solve the subproblems
      in the learning step, accelerating its convergence. The said algorithms could
      also be applied to FDDL and its extensions. The efficiencies of these algorithms
      are theoretically and experimentally verified by comparing their complexities and
      running time with those of other well-known dictionary learning methods.
      Experimental results on widely used image data sets establish the advantages of
      our method over the state-of-the-art dictionary learning methods.

PMID- 28742036
TI  - Study of Temporal Effects on Subjective Video Quality of Experience.
AB  - HTTP adaptive streaming is being increasingly deployed by network content
      providers, such as Netflix and YouTube. By dividing video content into data
      chunks encoded at different bitrates, a client is able to request the appropriate
      bitrate for the segment to be played next based on the estimated network
      conditions. However, this can introduce a number of impairments, including
      compression artifacts and rebuffering events, which can severely impact an end
      user's quality of experience (QoE). We have recently created a new video quality
      database, which simulates a typical video streaming application, using long video
      sequences and interesting Netflix content. Going beyond previous efforts, the new
      database contains highly diverse and contemporary content, and it includes the
      subjective opinions of a sizable number of human subjects regarding the effects
      on QoE of both rebuffering and compression distortions. We observed that
      rebuffering is always obvious and unpleasant to subjects, while bitrate changes
      may be less obvious due to content-related dependencies. Transient bitrate drops
      were preferable over rebuffering only on low complexity video content, while
      consistently low bitrates were poorly tolerated. We evaluated different objective
      video quality assessment algorithms on our database and found that objective
      video quality models are unreliable for QoE prediction on videos suffering from
      both rebuffering events and bitrate changes. This implies the need for more
      general QoE models that take into account objective quality models, rebuffering
      aware information, and memory. The publicly available video content as well as
      metadata for all of the videos in the new database can be found at
      http://live.ece.utexas.edu/research/LIVE_NFLXStudy/nflx_index.html.

PMID- 28742037
TI  - Temporal Coherence-Based Deblurring Using Non-Uniform Motion Optimization.
AB  - Non-uniform motion blur due to object movement or camera jitter is a common
      phenomenon in videos. However, the state-of-the-art video deblurring methods used
      to deal with this problem can introduce artifacts, and may sometimes fail to
      handle motion blur due to the movements of the object or the camera. In this
      paper, we propose a non-uniform motion model to deblur video frames. The proposed
      method is based on superpixel matching in the video sequence to reconstruct sharp
      frames from blurry ones. To identify a suitable sharp superpixel to replace a
      blurry one, we enrich the search space with a non-uniform motion blur kernel, and
      use a generalized PatchMatch algorithm to handle rotation, scale, and blur
      differences in the matching step. Instead of using pixel-based or regular patch
      based representation, we adopt a superpixel-based representation, and use color
      and motion to gather similar pixels. Our non-uniform motion blur kernels are
      estimated from the motion field of these superpixels, and our spatially varying
      motion model considers spatial and temporal coherence to find sharp superpixels.
      Experimental results showed that the proposed method can reconstruct sharp video
      frames from blurred frames caused by complex object and camera movements, and
      performs better than the state-of-the-art methods.

PMID- 28742038
TI  - Understanding Symmetric Smoothing Filters: A Gaussian Mixture Model Perspective.
AB  - Many patch-based image denoising algorithms can be formulated as applying a
      smoothing filter to the noisy image. Expressed as matrices, the smoothing filters
      must be row normalized, so that each row sums to unity. Surprisingly, if we apply
      a column normalization before the row normalization, the performance of the
      smoothing filter can often be significantly improved. Prior works showed that
      such performance gain is related to the Sinkhorn-Knopp balancing algorithm, an
      iterative procedure that symmetrizes a row-stochastic matrix to a doubly
      stochastic matrix. However, a complete understanding of the performance gain
      phenomenon is still lacking. In this paper, we study the performance gain
      phenomenon from a statistical learning perspective. We show that Sinkhorn-Knopp
      is equivalent to an expectation-maximization (EM) algorithm of learning a
      Gaussian mixture model of the image patches. By establishing the correspondence
      between the steps of Sinkhorn-Knopp and the EM algorithm, we provide a
      geometrical interpretation of the symmetrization process. This observation allows
      us to develop a new denoising algorithm called Gaussian mixture model symmetric
      smoothing filter (GSF). GSF is an extension of the Sinkhorn-Knopp and is a
      generalization of the original smoothing filters. Despite its simple formulation,
      GSF outperforms many existing smoothing filters and has a similar performance
      compared with several state-of-the-art denoising algorithms.

PMID- 28742039
TI  - Reconstructing Interlaced High-Dynamic-Range Video Using Joint Learning.
AB  - For extending the dynamic range of video, it is a common practice to capture
      multiple frames sequentially with different exposures and combine them to extend
      the dynamic range of each video frame. However, this approach results in typical
      ghosting artifacts due to fast and complex motion in nature. As an alternative,
      video imaging with interlaced exposures has been introduced to extend the dynamic
      range. However, the interlaced approach has been hindered by jaggy artifacts and
      sensor noise, leading to concerns over image quality. In this paper, we propose a
      data-driven approach for jointly solving two specific problems of deinterlacing
      and denoising that arise in interlaced video imaging with different exposures.
      First, we solve the deinterlacing problem using joint dictionary learning via
      sparse coding. Since partial information of detail in differently exposed rows is
      often available via interlacing, we make use of the information to reconstruct
      details of the extended dynamic range from the interlaced video input. Second, we
      jointly solve the denoising problem by tailoring sparse coding to better handle
      additive noise in low-/high-exposure rows, and also adopt multiscale homography
      flow to temporal sequences for denoising. We anticipate that the proposed method
      will allow for concurrent capture of higher dynamic range video frames without
      suffering from ghosting artifacts. We demonstrate the advantages of our
      interlaced video imaging compared with the state-of-the-art high-dynamic-range
      video methods.

PMID- 28742040
TI  - An hp-Adaptive Discretization Algorithm for Signed Distance Field Generation.
AB  - In this paper we present an hp-adaptive algorithm to generate discrete higher
      order polynomial Signed Distance Fields (SDFs) on axis-aligned hexahedral grids
      from manifold polygonal input meshes. Using an orthonormal polynomial basis, we
      efficiently fit the polynomials to the underlying signed distance function on
      each cell. The proposed error-driven construction algorithm is globally adaptive
      and iteratively refines the SDFs using either spatial subdivision ( h-refinement)
      following an octree scheme or by cell-wise adaption of the polynomial
      approximation's degree ( p-refinement). We further introduce a novel decision
      criterion based on an error-estimator in order to decide whether to apply p- or h
      refinement. We demonstrate that our method is able to construct more accurate
      SDFs at significantly lower memory consumption compared to previous approaches.
      While the cell-wise polynomial approximation will result in highly accurate SDFs,
      it can not be guaranteed that the piecewise approximation is continuous over cell
      interfaces. Therefore, we propose an optimization-based post-processing step in
      order to weakly enforce continuity. Finally, we apply our generated SDFs as
      collision detector to the physically-based simulation of geometrically highly
      complex solid objects in order to demonstrate the practical relevance and
      applicability of our method.

PMID- 28742041
TI  - ADMM ? Projective Dynamics: Fast Simulation of Hyperelastic Models with Dynamic
      Constraints.
AB  - We apply the alternating direction method of multipliers (ADMM) optimization
      algorithm to implicit time integration of elastic bodies, and show that the
      resulting method closely relates to the recently proposed projective dynamics
      algorithm. However, as ADMM is a general purpose optimization algorithm
      applicable to a broad range of objective functions, it permits the use of
      nonlinear constitutive models and hard constraints while retaining the speed,
      parallelizability, and robustness of projective dynamics. We further extend the
      algorithm to improve the handling of dynamically changing constraints such as
      sliding and contact, while maintaining the benefits of a constant, prefactored
      system matrix. We demonstrate the benefits of our algorithm on several examples
      that include cloth, collisions, and volumetric deformable bodies with nonlinear
      elasticity and skin sliding effects.

PMID- 28742042
TI  - How Do Users Map Points Between Dissimilar Shapes?
AB  - Finding similar points in globally or locally similar shapes has been studied
      extensively through the use of various point descriptors or shape-matching
      methods. However, little work exists on finding similar points in dissimilar
      shapes. In this paper, we present the results of a study where users were given
      two dissimilar two-dimensional shapes and asked to map a given point in the first
      shape to the point in the second shape they consider most similar. We find that
      user mappings in this study correlate strongly with simple geometric
      relationships between points and shapes. To predict the probability distribution
      of user mappings between any pair of simple two-dimensional shapes, two distinct
      statistical models are defined using these relationships. We perform a thorough
      validation of the accuracy of these predictions and compare our models
      qualitatively and quantitatively to well-known shape-matching methods. Using our
      predictive models, we propose an approach to map objects or procedural content
      between different shapes in different design scenarios.

PMID- 28742043
TI  - Mixed-Modality Stimulation to Evoke Two Modalities Simultaneously in One Channel
      for Electrocutaneous Sensory Feedback.
AB  - One of the long-standing challenges in upper limb prosthetics is restoring the
      sensory feedback that is missing due to amputation. Two approaches have
      previously been presented to provide various types of sensory information to
      users, namely, multi-modality sensory feedback and using an array of single
      modality stimulators. However, the feedback systems used in these approaches were
      too bulky to be embedded in prosthesis sockets. In this paper, we propose an
      electrocutaneous sensory feedback method that is capable of conveying two
      modalities simultaneously with only one electrode. The stimulation method, which
      we call mixed-modality stimulation, utilizes the phenomenon in which the
      superposition of two electric pulse trains of different frequencies is able to
      evoke two different modalities (i.e., pressure and tapping) at the same time. We
      conducted psychophysical experiments in which healthy subjects were required to
      recognize the intensity of pressure or the frequency of tapping from mixed
      modality or two-channel stimulations. The results demonstrated that the subjects
      were able to discriminate the features of the two modalities in one electrode
      during mixed-modality stimulation and that the accuracies of successful
      recognitions (mean +/- standard deviation) for the two feedback variables were
      84.3 +/- 7% for mixed-modality stimulation and 89.5 +/- 6% for two-channel dual
      modality stimulation, showing no statistically significant difference. Therefore,
      mixed-modality stimulation is an attractive method for modulating two modalities
      independently with only one electrode, and it could be used for implementing a
      compact sensory feedback system that is able to provide two different types of
      sensory information from prosthetics.

PMID- 28742044
TI  - Multipolar Field Shaping in a Suprachoroidal Visual Prosthesis.
AB  - Visual prostheses are now an available mobility aid for patients blinded by
      degenerative retinal diseases. However, the spatial resolution of existing
      devices is still insufficient to deliver normal levels of mobility vision without
      stimulation strategies, which enable existing devices to deliver several
      different percepts per stimulation site. A stimulation strategy, in which field
      shaping is achieved by incorporating multipolar (bipolar and tripolar)
      stimulation could convey additional information to a user of a visual prosthesis,
      as compared with monopolar stimulation, is investigated. Electrical stimulus
      response thresholds were simulated using morphologically and physiologically
      accurate cable models of human retinal ganglion cell (RGC) axons. From the
      population response patterns which could be evoked in simulation, multipolar
      field-shaping stimulation from one location could convey as much information as
      monopolar array stimulation. This result is confirmed in vitro by applying a
      Bayesian classification analysis to multielectrode array recordings of RGC
      population responses to extracellular stimulation. In vitro recorded population
      responses to individual stimuli in vitro could be used to train a Baysian
      classifier, which could correctly identify individual stimuli as predicted by the
      simulated population responses. In both simulation and in vitro experiments,
      monopolar thresholds were not significantly different to multipolar thresholds.

PMID- 28742045
TI  - A Multi-Class Tactile Brain-Computer Interface Based on Stimulus-Induced
      Oscillatory Dynamics.
AB  - We proposed a multi-class tactile brain-computer interface that utilizes stimulus
      induced oscillatory dynamics. It was hypothesized that somatosensory attention
      can modulate tactile-induced oscillation changes, which can decode different
      sensation attention tasks. Subjects performed four tactile attention tasks,
      prompted by cues presented in random order and while both wrists were
      simultaneously stimulated: 1) selective sensation on left hand (SS-L); 2)
      selective sensation on right hand (SS-R); 3) bilateral selective sensation; and
      4) selective sensation suppressed or idle state (SS-S). The classification
      accuracy between SS-L and SS-R (79.9 +/- 8.7%) was comparable with that of a
      previous tactile BCI system based on selective sensation. Moreover, the accuracy
      could be improved to an average of 90.3 +/- 4.9% by optimal class-pair and
      frequency-band selection. Three-class discrimination had an accuracy of 75.2 +/-
      8.3%, with the best discrimination reached for the classes SS-L, SS-R, and SS-S.
      Finally, four classes were classified with an accuracy of 59.4 +/- 7.3%. These
      results show that the proposed system is a promising new paradigm for multi-class
      BCI.

PMID- 28742046
TI  - A Fast Algorithm for Analysis of Molecular Communication in Artificial Synapse.
AB  - In this paper, we analyze molecular communications (MCs) in a proposed artificial
      synapse (AS), whose main difference from biological synapses (BSs) is that it is
      closed, i.e., transmitter molecules cannot diffuse out from AS. Such a setup has
      both advantages and disadvantages. Besides higher structural stability, being
      closed, AS never runs out of transmitters. Thus, MC in AS is disconnected from
      outer environment, which is very desirable for possible intra-body applications.
      On the other hand, clearance of transmitters from AS has to be achieved by
      transporter molecules on the presynaptic membrane of AS. Except from these
      differences, rest of AS content is taken to be similar to that of a glutamatergic
      BS. Furthermore, in place of commonly used Monte Carlo-based random walk
      experiments, we derive a deterministic algorithm that attacks for expected values
      of desired parameters such as evolution of receptor states. To assess validity of
      our algorithm, we compare its results with average results of an ensemble of
      Monte Carlo experiments, which shows near exact match. Moreover, our approach
      requires significantly less amount of computation compared with Monte Carlo
      approach, making it useful for parameter space exploration necessary for
      optimization in design of possible MC devices, including but not limited to AS.
      Results of our algorithm are presented in case of single quantal release only,
      and they support that MC in closed AS with elevated uptake has similar properties
      to that in BS. In particular, similar to glutamatergic BSs, the quantal size and
      the density of receptors are found to be main sources of synaptic plasticity. On
      the other hand, the proposed model of AS is found to have slower decaying
      transients of receptor states than BSs, especially desensitized ones, which is
      due to prolonged clearance of transmitters from AS.

PMID- 28742047
TI  - Optimal Broadband Noise Matching to Inductive Sensors: Application to Magnetic
      Particle Imaging.
AB  - Inductive sensor-based measurement techniques are useful for a wide range of
      biomedical applications. However, optimizing the noise performance of these
      sensors is challenging at broadband frequencies, owing to the frequency-dependent
      reactance of the sensor. In this work, we describe the fundamental limits of
      noise performance and bandwidth for these sensors in combination with a low-noise
      amplifier. We also present three equivalent methods of noise matching to
      inductive sensors using transformer-like network topologies. Finally, we apply
      these techniques to improve the noise performance in magnetic particle imaging, a
      new molecular imaging modality with excellent detection sensitivity. Using a
      custom noise-matched amplifier, we experimentally demonstrate an 11-fold
      improvement in noise performance in a small animal magnetic particle imaging
      scanner.

PMID- 28742048
TI  - Broad Learning System: An Effective and Efficient Incremental Learning System
      Without the Need for Deep Architecture.
AB  - Broad Learning System (BLS) that aims to offer an alternative way of learning in
      deep structure is proposed in this paper. Deep structure and learning suffer from
      a time-consuming training process because of a large number of connecting
      parameters in filters and layers. Moreover, it encounters a complete retraining
      process if the structure is not sufficient to model the system. The BLS is
      established in the form of a flat network, where the original inputs are
      transferred and placed as "mapped features" in feature nodes and the structure is
      expanded in wide sense in the "enhancement nodes." The incremental learning
      algorithms are developed for fast remodeling in broad expansion without a
      retraining process if the network deems to be expanded. Two incremental learning
      algorithms are given for both the increment of the feature nodes (or filters in
      deep structure) and the increment of the enhancement nodes. The designed model
      and algorithms are very versatile for selecting a model rapidly. In addition,
      another incremental learning is developed for a system that has been modeled
      encounters a new incoming input. Specifically, the system can be remodeled in an
      incremental way without the entire retraining from the beginning. Satisfactory
      result for model reduction using singular value decomposition is conducted to
      simplify the final structure. Compared with existing deep neural networks,
      experimental results on the Modified National Institute of Standards and
      Technology database and NYU NORB object recognition dataset benchmark data
      demonstrate the effectiveness of the proposed BLS.

PMID- 28742049
TI  - Reduced- and Full-Order Observers for Delayed Genetic Regulatory Networks.
AB  - This paper is centered upon the state estimation for delayed genetic regulatory
      networks. Our aim is at estimating the concentrations of mRNAs and proteins by
      designing reduced-order and full-order state observers based on available network
      outputs. We introduce a Lyapunov-Krasovskii functional including quadruplicate
      integrals, and estimate its derivative by employing the Wirtinger-type integral
      inequalities, reciprocal convex technique, and convex technique. From which,
      delay-dependent sufficient conditions, in the form of linear matrix inequalities
      (LMIs), are investigated to ensure that the resultant error system is
      asymptotically stable. One can verify these conditions by utilizing the MATLAB
      Toolboxes LMI or YALMIP. In addition, the gains of reduced-order and full-order
      observers are represented by the feasible solutions of the LMIs, and thereby, the
      concrete expressions of the desired reduced-order and full-order state observers
      are presented. Finally, the simulation results of a numerical example are
      demonstrated, which explains the validity of the proposed method.

PMID- 28742050
TI  - Asymptotic Tracking Controller Design for Nonlinear Systems With Guaranteed
      Performance.
AB  - In this paper, a novel adaptive control strategy is presented for the tracking
      control of a class of multi-input-multioutput uncertain nonlinear systems with
      external disturbances to place user-defined time-varying constraints on the
      system state. Our contribution includes a step forward beyond the usual
      stabilization result to show that the states of the plant converge
      asymptotically, as well as remain within user-defined time-varying bounds. To
      achieve the new results, an error transformation technique is first established
      to generate an equivalent nonlinear system from the original one, whose
      asymptotic stability guarantees both the satisfaction of the time-varying
      restrictions and the asymptotic tracking performance of the original system. The
      uncertainties of the transformed system are overcome by an online neural network
      (NN) approximator, while the external disturbances and NN reconstruction error
      are compensated by the robust integral of the sign of the error signal. Via
      standard Lyapunov method, asymptotic tracking performance is theoretically
      guaranteed, and all the closed-loop signals are bounded. The requirement for a
      prior knowledge of bounds of uncertain terms is relaxed. Finally, simulation
      results demonstrate the merits of the proposed controller.

PMID- 28742051
TI  - Cooperative Tracking of Networked Agents With a High-Dimensional Leader:
      Qualitative Analysis and Performance Evaluation.
AB  - Cooperative consensus tracking and its -gain performance is investigated in this
      paper for a class of multiple agent systems (MASs) in the presence of a single
      high-dimensional leader. Compared with the traditional models for MASs, the
      inherent dynamics of the leader are allowed to be different with those of the
      followers in the present framework, which is thus much more favorable in various
      practical applications. A new kind of distributed controllers associated with a
      reduced-order state observer are designed for each follower to track the high
      dimensional leader under directed switching topology. With the help of -matrix
      theory and stability analysis methods of switched systems, some efficient
      criteria are derived for cooperative consensus tracking of MASs without any
      external disturbance under directed switching topology. Theoretical analysis is
      further extended to the case of consensus tracking for MASs subject to unknown
      external disturbances by showing that, a finite -gain performance for tracking
      errors against external disturbances can be ensured if some suitable conditions
      are satisfied. At last, the synthesis issue of designing an observer-based
      controller to achieve a prescribed -gain performance for consensus tracking is
      studied by using tools from control theory, where the underlying topology is
      assumed to be undirected and fixed. The effectiveness of theoretical results is
      verified by performing numerical simulations.

PMID- 28742052
TI  - A semi-analytical model of a time reversal cavity for high-amplitude focused
      ultrasound applications.
AB  - Time reversal cavities (TRC) have been proposed as an efficient approach for 3D
      ultrasound therapy. They allow the precise spatio-temporal focusing of high-power
      ultrasound pulses within a large region of interest with a low number of
      transducers. Leaky TRCs are usually built by placing a multiple scattering
      medium, such as a random rod forest, in a reverberating cavity, and the final
      peak pressure gain of the device only depends on the temporal length of its
      impulse response. Such multiple scattering in a reverberating cavity is a complex
      phenomenon, and optimisation of the device's gain is usually a cumbersome
      process, mostly empirical, and requiring numerical simulations with extremely
      long computation times. In this paper, we present a semi-analytical model for the
      fast optimisation of a TRC. This model decouples ultrasound propagation in an
      empty cavity and multiple scattering in a multiple scattering medium. It was
      validated numerically and experimentally using a 2D-TRC and numerically using a
      3D-TRC. Finally, the model was used to determine rapidly the optimal parameters
      of the 3D-TRC which had been confirmed by numerical simulations.

PMID- 28742053
TI  - Submillimeter ionoacoustic range determination for protons in water at a clinical
      synchrocyclotron.
AB  - Proton ranges in water between 145 MeV to 227 MeV initial energy have been
      measured at a clinical superconducting synchrocyclotron using the acoustic signal
      induced by the ion dose deposition (ionoacoustic effect). Detection of ultrasound
      waves was performed by a very sensitive hydrophone and signals were stored in a
      digital oscilloscope triggered by secondary prompt gammas. The ionoacoustic range
      measurements were compared to existing range data from a calibrated range
      detector setup on-site and agreement of better than 1 mm was found at a Bragg
      peak dose of about 10 Gy for 220 MeV initial proton energy, compatible with the
      experimental errors. Ionoacoustics has thus the potential to measure the Bragg
      peak position with submillimeter accuracy during proton therapy, possibly
      correlated with ultrasound tissue imaging.

PMID- 28742054
TI  - Laue lens for radiotherapy applications through a focused hard x-ray beam: a
      feasibility study on requirements and tolerances.
AB  - Focusing a hard x-ray beam would represent an innovative technique for tumour
      treatment, since such a beam may deliver a dose to a tumour located at a given
      depth under the skin, sparing the surrounding healthy cells. A detailed study of
      a focusing system for hard x-ray aimed at radiotherapy is presented here. Such a
      focusing system, named Laue lens, exploits x-ray diffraction and consists of a
      series of crystals disposed as concentric rings capable of concentrating a flux
      of x-rays towards a focusing point. A feasibility study regarding the positioning
      tolerances of the crystalline optical elements has been carried out. It is shown
      that a Laue lens can effectively be used in the context of radiotherapy for
      tumour treatments provided that the mounting errors are below certain values,
      which are reachable in the modern micromechanics. An extended survey based on an
      analytical approach and on simulations is presented for precisely estimating all
      the contributions of each mounting error, analysing their effect on the focal
      spot of the Laue lens. Finally, a simulation for evaluating the released dose in
      a water phantom is shown.

PMID- 28742055
TI  - Kinetic validation of the LiMAx test during 10 000 intravenous 13C-methacetin
      breath tests.
AB  - The maximal liver function capacity (LiMAx) test, a novel 13C-methacetin breath
      test, has proven clinical validity in determining hepatic metabolic capacity. In
      contrast to prior 13C-methacetin breath test protocols, the LiMAx test is
      performed by intravenous body-weight-adjusted substrate administration.
      Furthermore, the DOB kinetics (delta over baseline of the time-dependent exhaled
      13CO2/12CO2 ratio) are measured online at the bedside with a high time resolution
      in order to determine the maximum DOB. The aim of this study was to analyze the
      recorded DOB kinetics in a large population for further refinement of the test
      protocol. Two new methods of kinetic analysis are proposed in this article: the
      time dependency of the DOB kinetics and the time interval until half of the DOB
      maximum. A total of 10 100 LiMAx tests on 8483 patients performed during routine
      clinics at eight centers were available. The kinetic analysis revealed a specific
      pattern of DOB kinetics depending upon LiMAx result. In addition, potential co
      factors for DOB kinetics, such as weight, height, gender and age, were analyzed,
      yielding a potential influence of gender and smoking behavior. Both the specific
      patterns and the proposed kinetic analysis have the potential to further improve
      the sensitivity and specificity of the test and its clinical applicability by
      shortening its duration.

PMID- 28742056
TI  - Monte Carlo simulations of skin exposure to electromagnetic field from 10 GHz to
      1 THz.
AB  - In this study, we present an assessment of human-body exposure to an
      electromagnetic field at frequencies ranging from 10 GHz to 1 THz. The energy
      absorption and temperature elevation were assessed by solving boundary value
      problems of the one-dimensional Maxwell equations and a bioheat equation for a
      multilayer plane model. Dielectric properties were measured [Formula: see text]
      at frequencies of up to 1 THz at body temperature. A Monte Carlo simulation was
      conducted to assess variations of the transmittance into a skin surface and
      temperature elevation inside a body by considering the variation of the tissue
      thickness due to individual differences among human bodies. Furthermore, the
      impact of the dielectric properties of adipose tissue on temperature elevation,
      for which large discrepancies between our present measurement results and those
      in past works were observed, was also examined. We found that the dielectric
      properties of adipose tissue do not impact on temperature elevation at
      frequencies over 30 GHz. The potential risk of skin burn was discussed on the
      basis of the temperature elevation in millimeter-wave and terahertz-wave
      exposure. Furthermore, the consistency of the basic restrictions in the
      international guidelines set by ICNIRP was discussed.

PMID- 28742057
TI  - Effect of photodynamic therapy in the reduction of halitosis in patients with
      multiple sclerosis: clinical trial.
AB  - Smell and odours play a vital role in social interaction. Halitosis is a social
      problem that affects one third of the population, causing a negative impact on
      the quality of life. There is little knowledge on the prevalence and management
      of halitosis in multiple sclerosis (MS) patients. The present study aims to
      evaluate the presence of halitosis in patients with MS when compared to a control
      group, and also evaluate treatment of the problem with antimicrobial photodynamic
      therapy (aPDT). This is a case-control clinical study in which 60 patients were
      evaluated: 30 MS patients in treatment at the Specialties Clinic School of
      Medicine, and 30 healthy patients, matched in age and gender for the control
      group. Data was collected on the duration of the disease as well as the degree of
      disability and medication use in the MS group. For all patients, halitosis was
      assessed with Oral ChromaTM. Individuals with halitosis underwent treatment with
      tongue scraping and aPDT. The photosensitizer was methylene blue (0.005%) and a
      THERAPY XT-EC(r) laser (660 nm, 9 J, 100 mW for 90 s per point, 320 J cm-2, 3537
      mW cm-2) was used. Six points 1 cm apart from each other were irradiated in the
      tongue dorsum. There was a positive correlation between the disability and
      disease duration. No parameter was correlated with halitosis. Patients with MS
      have higher levels of SH2 compounds when compared to the control group (p =
      0.003, Mann-Whitney), but after aPDT both groups significantly reduced the levels
      to under the halitosis threshold. The aPDT scraping treatment was effective in
      the immediate reduction of halitosis in both groups.

PMID- 28742058
TI  - ITO with embedded silver grids as transparent conductive electrodes for large
      area organic solar cells.
AB  - In this work, development of semi-transparent electrodes for efficient large area
      organic solar cells (OSCs) has been demonstrated. Electron beam evaporated silver
      grids were embedded in commercially available ITO coatings on glass, through a
      standard negative photolithography process, in order to improve the conductivity
      of planar ITO substrates. The fabricated electrodes with embedded line and square
      patterned Ag grids reduced the sheet resistance of ITO by 25% and 40%,
      respectively, showing optical transmittance drops of less than 6% within the
      complete visible light spectrum for both patterns. Solution processed bulk
      heterojunction OSCs based on PTB7:[70]PCBM were fabricated on top of these
      electrodes with cell areas of 4.38 cm2, and the performance of these OSCs was
      compared to reference cells fabricated on pure ITO electrodes. The Fill Factor
      (FF) of the large-scale OSCs fabricated on ITO with embedded Ag grids was
      enhanced by 18% for the line grids pattern and 30% for the square grids pattern
      compared to that of the reference OSCs. The increase in the FF was directly
      correlated to the decrease in the series resistance of the OSCs. The maximum
      power conversion efficiency (PCE) of the OSCs was measured to be 4.34%, which is
      23% higher than the PCE of the reference OSCs. As the presented method does not
      involve high temperature processing, it could be considered a general approach
      for development of large area organic electronics on solvent resistant, flexible
      substrates.

PMID- 28742059
TI  - Spanning the scales of mechanical metamaterials using time domain simulations in
      transformed crystals, graphene flakes and structured soils.
AB  - We begin with a brief historical survey of discoveries of quasi-crystals and
      graphene, and then introduce the concept of transformation crystallography, which
      consists of the application of geometric transforms to periodic structures. We
      consider motifs with three-fold, four-fold and six-fold symmetries according to
      the crystallographic restriction theorem. Furthermore, we define motifs with five
      fold symmetry such as quasi-crystals generated by a cut-and-projection method
      from periodic structures in higher-dimensional space. We analyze elastic wave
      propagation in the transformed crystals and (Penrose-type) quasi-crystals with
      the finite difference time domain freeware SimSonic. We consider geometric
      transforms underpinning the design of seismic cloaks with square, circular,
      elliptical and peanut shapes in the context of honeycomb crystals that can be
      viewed as scaled-up versions of graphene. Interestingly, the use of morphing
      techniques leads to the design of cloaks with interpolated geometries reminiscent
      of Victor Vasarely's artwork. Employing the case of transformed graphene-like
      (honeycomb) structures allows one to draw useful analogies between large-scale
      seismic metamaterials such as soils structured with columns of concrete or grout
      with soil and nanoscale biochemical metamaterials. We further identify
      similarities in designs of cloaks for elastodynamic and hydrodynamic waves and
      cloaks for diffusion (heat or mass) processes, as these are underpinned by
      geometric transforms. Experimental data extracted from field test analysis of
      soil structured with boreholes demonstrates the application of crystallography to
      large scale phononic crystals, coined as seismic metamaterials, as they might
      exhibit low frequency stop bands. This brings us to the outlook of mechanical
      metamaterials, with control of phonon emission in graphene through extreme
      anisotropy, attenuation of vibrations of suspension bridges via low frequency
      stop bands and the concept of transformed meta-cities. We conclude that these
      novel materials hold strong applications spanning different disciplines or across
      different scales from biophysics to geophysics.

PMID- 28742060
TI  - Suppressed Kondo effect and Kosterlitz-Thouless-type phase transition induced by
      level difference in a triple dot device.
AB  - Quantum dot system provides an ideal platform for quantum information processing,
      within which to demonstrate the quantum states is one of the most important issue
      for quantum simulation and quantum computation. In this paper, we report a
      peculiar electron state in a parallel triple dot device where the Ruderman-Kittel
      Kasuya-Yosida interaction is invalid when the level differences of the dots sweep
      into appropriate regime. This extraordinary tendency then results in an
      antiferromagnetic spin coupling between two of the dots and may lead to zero or
      full conductance, relying deeply on the relation of the two level spacings. e.g.
      when the level differences are kept equal, the Kondo effect is totally suppressed
      although the dots are triply occupied, since in this case a local inter-dot
      transport loop is found to play an important role in the transmission
      coefficient. By contrast, when the differences are retained symmetric, the Kondo
      peak reaches nearly to its unitary limit, owing to that the inter-dot transport
      process is significantly suppressed. To approach these problems, voltage
      controllable quantum phase transitions of Kosterlitz-Thouless type and first
      order are shown, and possible pictures related to the many-body effect and the
      effective Kondo model are given.

PMID- 28742061
TI  - Test study of boron nitride as a new detector material for dosimetry in high
      energy photon beams.
AB  - The aim of this test study is to check whether boron nitride (BN) might be
      applied as a detector material in high-energy photon-beam dosimetry. Boron
      nitride exists in various crystalline forms. Hexagonal boron nitride (h-BN)
      possesses high mobility of the electrons and holes as well as a high volume
      resistivity, so that ionizing radiation in the clinical range of the dose rate
      can be expected to produce a measurable electrical current at low background
      current. Due to the low atomic numbers of its constituents, its density (2.0 g cm
      3) similar to silicon and its commercial availability, h-BN appears as possibly
      suitable for the dosimetry of ionizing radiation. Five h-BN plates were contacted
      to triaxial cables, and the detector current was measured in a solid-state
      ionization chamber circuit at an applied voltage of 50 V. Basic dosimetric
      properties such as formation by pre-irradiation, sensitivity, reproducibility,
      linearity and temporal resolution were measured with 6 MV photon irradiation.
      Depth dose curves at quadratic field sizes of 10 cm and 40 cm were measured and
      compared to ionization chamber measurements. After a pre-irradiation with 6 Gy,
      the devices show a stable current signal at a given dose rate. The current
      voltage characteristic up to 400 V shows an increase in the collection efficiency
      with the voltage. The time-resolved detector current behavior during beam
      interrupts is comparable to diamond material, and the background current is
      negligible. The measured percentage depth dose curves at 10 cm  *  10 cm field
      size agreed with the results of ionization chamber measurements within  +/-2%.
      This is a first study of boron nitride as a detector material for high-energy
      photon radiation. By current measurements on solid ionization chambers made from
      boron nitride chips we could demonstrate that boron nitride is in principle
      suitable as a detector material for high-energy photon-beam dosimetry.

PMID- 28742062
TI  - A method to incorporate the effect of beam quality on image noise in a digitally
      reconstructed radiograph (DRR) based computer simulation for optimisation of
      digital radiography.
AB  - The use of computer simulated digital x-radiographs for optimisation purposes has
      become widespread in recent years. To make these optimisation investigations
      effective, it is vital simulated radiographs contain accurate anatomical and
      system noise. Computer algorithms that simulate radiographs based solely on the
      incident detector x-ray intensity ('dose') have been reported extensively in the
      literature. However, while it has been established for digital mammography that x
      ray beam quality is an important factor when modelling noise in simulated images
      there are no such studies for diagnostic imaging of the chest, abdomen and
      pelvis. This study investigates the influence of beam quality on image noise in a
      digital radiography (DR) imaging system, and incorporates these effects into a
      digitally reconstructed radiograph (DRR) computer simulator. Image noise was
      measured on a real DR imaging system as a function of dose (absorbed energy) over
      a range of clinically relevant beam qualities. Simulated 'absorbed energy' and
      'beam quality' DRRs were then created for each patient and tube voltage under
      investigation. Simulated noise images, corrected for dose and beam quality, were
      subsequently produced from the absorbed energy and beam quality DRRs, using the
      measured noise, absorbed energy and beam quality relationships. The noise images
      were superimposed onto the noiseless absorbed energy DRRs to create the final
      images. Signal-to-noise measurements in simulated chest, abdomen and spine images
      were within 10% of the corresponding measurements in real images. This compares
      favourably to our previous algorithm where images corrected for dose only were
      all within 20%.

PMID- 28742063
TI  - Demagnetization harmonic effects on the magnetization of granular systems on a
      macroscopic scale: the superconducting case.
AB  - A model has been developed to determine the effective ac magnetic response of
      magnetic systems, taking into account the demagnetization effects arising from
      the sample geometry which determine the out-of-phase components of the applied
      fundamental frequency and higher harmonic components. Indeed, demagnetization
      fields and their intermodulation can significantly affect the ac magnetic
      response. This approach provides a system of self-consistent linear equations
      relating the magnetic response to the external magnetic field by means of
      nonlinear magnetic susceptibility. The model is extended to the magnetic response
      of granular systems in terms of the contributions of the individual grains and of
      the whole sample in the presence of demagnetization effects of the whole sample
      and of the grains on a macroscopic scale. In particular, our model is applied to
      a granular superconducting system. The comparison between the performed numerical
      simulations and the experimental data shows that the demagnetization fields of
      the single grains and of the whole sample, and their intermodulation, are
      relevant if magnetic measurements are used to extract detailed information about
      the analyzed material.

PMID- 28742064
TI  - The effect of biosilver nanoparticles on different bacterial strains' metabolism
      reflected in their VOCs profiles.
AB  - The use of silver nanoparticles has become in recent years a growing interest for
      many researchers, due to their bacteriostatic and bactericidal properties and
      synergetic effects when they are used together with antibiotics, for an increased
      efficiency and less adverse reactions in the treatment of bacterial infections.
      Gas chromatography coupled with mass spectrometry (GC-MS), which is considered
      'the golden standard' in chemical analysis, has proven to be a reliable
      instrument, perfectly suitable for clinical analysis. In this work, three
      bacterial strains, Escherichia coli (E. coli), Klebsiella oxytoca (K. oxytoca)
      and Staphylococcus saccharolyticus (S. saccharolyticus) were treated with
      biosilver nanoparticles (bioAgNPs). Headspace and GC-MS analysis was used for the
      detection of volatile metabolites. We observed decreased amounts of alcohols and
      carbonyl components (mainly ketones) in K. oxytoca and S. saccharolyticus
      bacteria incubated with silver. In contrast, biosilver nanoparticles added to E.
      coli increased the amount of VOCs, mainly hydrocarbons and alcohols. Our results
      have successfully demonstrated that the treatment of bacterial strains with
      bioAgNPs has a direct influence on their VOC profiles, by modifying the number of
      metabolic markers. Connected with this, the inhibition of bacteria is supposed,
      and consequently both the bacteriostatic and/or bactericidal effects of bioAgNPs
      on all three bacterial strains investigated were revealed.

PMID- 28742065
TI  - The research infrastructure of Chinese foundations, a database for Chinese civil
      society studies.
AB  - This paper provides technical details and user guidance on the Research
      Infrastructure of Chinese Foundations (RICF), a database of Chinese foundations,
      civil society, and social development in general. The structure of the RICF is
      deliberately designed and normalized according to the Three Normal Forms. The
      database schema consists of three major themes: foundations' basic organizational
      profile (i.e., basic profile, board member, supervisor, staff, and related party
      tables), program information (i.e., program information, major program, program
      relationship, and major recipient tables), and financial information (i.e.,
      financial position, financial activities, cash flow, activity overview, and large
      donation tables). The RICF's data quality can be measured by four criteria: data
      source reputation and credibility, completeness, accuracy, and timeliness. Data
      records are properly versioned, allowing verification and replication for
      research purposes.

PMID- 28742066
TI  - A comprehensive data set of lake surface water temperature over the Tibetan
      Plateau derived from MODIS LST products 2001-2015.
AB  - Lake surface water temperature (LSWT) is sensitive to long-term changes in
      thermal structure of lakes and regional air temperature. In the context of global
      climate change, recent studies showed a significant warming trend of LSWT based
      on investigating 291 lakes (71% are large lakes, >=50 km2 each) globally.
      However, further efforts are needed to examine variation in LSWT at finer
      regional spatial and temporal scales. The Tibetan Plateau (TP), known as 'the
      Roof of the World' and 'Asia's water towers', exerts large influences on and is
      sensitive to regional and even global climates. Aiming to examine detailed
      changing patterns and potential driven mechanisms for temperature variations of
      lakes across the TP region, this paper presents the first comprehensive data set
      of 15-year (2001-2015) nighttime and daytime LSWT for 374 lakes (>=10 km2 each),
      using MODIS (Moderate Resolution Imaging Spectroradiometer) Land Surface
      Temperature (LST) products as well as four lake boundary shapefiles (i.e., 2002,
      2005, 2009, and 2014) derived from Landsat/CBERS/GaoFen-1 satellite images. The
      data set itself reveals significant information on LSWT and its changes over the
      TP and is an indispensable variable for numerous applications related to climate
      change, water budget analysis (particularly lake evaporation), water storage
      changes, glacier melting and permafrost degradation, etc.

PMID- 28742067
TI  - Long-term microdystrophin gene therapy is effective in a canine model of Duchenne
      muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is an incurable X-linked muscle-wasting disease
      caused by mutations in the dystrophin gene. Gene therapy using highly functional
      microdystrophin genes and recombinant adeno-associated virus (rAAV) vectors is an
      attractive strategy to treat DMD. Here we show that locoregional and systemic
      delivery of a rAAV2/8 vector expressing a canine microdystrophin (cMD1) is
      effective in restoring dystrophin expression and stabilizing clinical symptoms in
      studies performed on a total of 12 treated golden retriever muscular dystrophy
      (GRMD) dogs. Locoregional delivery induces high levels of microdystrophin
      expression in limb musculature and significant amelioration of histological and
      functional parameters. Systemic intravenous administration without
      immunosuppression results in significant and sustained levels of microdystrophin
      in skeletal muscles and reduces dystrophic symptoms for over 2 years. No toxicity
      or adverse immune consequences of vector administration are observed. These
      studies indicate safety and efficacy of systemic rAAV-cMD1 delivery in a large
      animal model of DMD, and pave the way towards clinical trials of rAAV
      microdystrophin gene therapy in DMD patients.

PMID- 28742068
TI  - A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice
      and fetuses.
AB  - Zika virus (ZIKV), a re-emerging flavivirus associated with neurological
      disorders, has spread rapidly to more than 70 countries and territories. However,
      no specific vaccines or antiviral drugs are currently available to prevent or
      treat ZIKV infection. Here we report that a synthetic peptide derived from the
      stem region of ZIKV envelope protein, designated Z2, potently inhibits infection
      of ZIKV and other flaviviruses in vitro. We show that Z2 interacts with ZIKV
      surface protein and disrupts the integrity of the viral membrane. Z2 can
      penetrate the placental barrier to enter fetal tissues and is safe for use in
      pregnant mice. Intraperitoneal administration of Z2 inhibits vertical
      transmission of ZIKV in pregnant C57BL/6 mice and protects type I or type I/II
      interferon receptor-deficient mice against lethal ZIKV challenge. Thus, Z2 has
      potential to be further developed as an antiviral treatment against ZIKV
      infection in high-risk populations, particularly pregnant women.

PMID- 28742069
TI  - Nematode grazing promotes bacterial community dynamics in soil at the aggregate
      level.
AB  - Nematode predation has important roles in determining bacterial community
      composition and dynamics, but the extent of the effects remains largely
      rudimentary, particularly in natural environment settings. Here, we investigated
      the complex microbial-microfaunal interactions in the rhizosphere of maize grown
      in red soils, which were derived from four long-term fertilization regimes. Root
      free rhizosphere soil samples were separated into three aggregate fractions
      whereby the abundance and community composition were examined for nematode and
      total bacterial communities. A functional group of alkaline phosphomonoesterase
      (ALP) producing bacteria was included to test the hypothesis that nematode
      grazing may significantly affect specific bacteria-mediated ecological functions,
      that is, organic phosphate cycling in soil. Results of correlation analysis,
      structural equation modeling and interaction networks combined with laboratory
      microcosm experiments consistently indicated that bacterivorous nematodes
      enhanced bacterial diversity, and the abundance of bacterivores was positively
      correlated with bacterial biomass, including ALP-producing bacterial abundance.
      Significantly, such effects were more pronounced in large macroaggregates than in
      microaggregates. There was a positive correlation between the most dominant
      bacterivores Protorhabditis and the ALP-producing keystone 'species'
      Mesorhizobium. Taken together, these findings implicate important roles of
      nematodes in stimulating bacterial dynamics in a spatially dependent manner.

PMID- 28742070
TI  - Growth arrest and a persister state enable resistance to osmotic shock and
      facilitate dissemination of Vibrio cholerae.
AB  - Vibrio cholerae is a water-borne bacterial pathogen and causative agent of
      cholera. Although V. cholerae is a halophile, it can survive in fresh water, and
      this has a major role in cholera epidemics through consumption of contaminated
      water and subsequent fecal-oral spread. After dissemination from humans back into
      fresh water, V. cholerae encounters limited nutrient availability and an abrupt
      drop in conductivity but little is known about how V. cholerae adapts to, and
      survives in this environment. In this work, by abolishing or altering the
      expression of V. cholerae genes in a high-throughput manner, we observed that
      many osmotic shock tolerant mutants exhibited slowed or arrested growth, and/or
      generated a higher proportion of persister cells. In addition, we show that
      growth-arrested V. cholerae, including a persister subpopulation, are generated
      during infection of the intestinal tract and together allow for the successful
      dissemination to fresh water. Our results suggest that growth-arrested and
      persister subpopulations enable survival of V. cholerae upon shedding to the
      aquatic environment.

PMID- 28742071
TI  - dRep: a tool for fast and accurate genomic comparisons that enables improved
      genome recovery from metagenomes through de-replication.
AB  - The number of microbial genomes sequenced each year is expanding rapidly, in part
      due to genome-resolved metagenomic studies that routinely recover hundreds of
      draft-quality genomes. Rapid algorithms have been developed to comprehensively
      compare large genome sets, but they are not accurate with draft-quality genomes.
      Here we present dRep, a program that reduces the computational time for pairwise
      genome comparisons by sequentially applying a fast, inaccurate estimation of
      genome distance, and a slow, accurate measure of average nucleotide identity.
      dRep achieves a 28 * increase in speed with perfect recall and precision when
      benchmarked against previously developed algorithms. We demonstrate the use of
      dRep for genome recovery from time-series datasets. Each metagenome was assembled
      separately, and dRep was used to identify groups of essentially identical genomes
      and select the best genome from each replicate set. This resulted in recovery of
      significantly more and higher-quality genomes compared to the set recovered using
      co-assembly.

PMID- 28742072
TI  - Phaeoviruses discovered in kelp (Laminariales).
AB  - Phaeoviruses are latent double-stranded DNA viruses that insert their genomes
      into those of their brown algal (Phaeophyceae) hosts. So far these viruses are
      known only from members of the Ectocarpales, which are small and short-lived
      macroalgae. Here we report molecular and morphological evidence for a new
      Phaeovirus cluster, referred to as sub-group C, infecting kelps (Laminariales) of
      the genera Laminaria and Saccharina, which are ecologically and commercially
      important seaweeds. Epifluorescence and TEM observations indicate that the
      Laminaria digitata Virus (LdigV), the type species of sub-group C, targets the
      host nucleus for its genome replication, followed by gradual degradation of the
      chloroplast and assembly of virions in the cytoplasm of both vegetative and
      reproductive cells. This study is the first to describe phaeoviruses in kelp. In
      the field, these viruses infected two thirds of their host populations; however,
      their biological impact remains unknown.

PMID- 28742073
TI  - Biological nitrogen fixation in the oxygen-minimum region of the eastern tropical
      North Pacific ocean.
AB  - Biological nitrogen fixation (BNF) was investigated above and within the oxygen
      depleted waters of the oxygen-minimum zone of the Eastern Tropical North Pacific
      Ocean. BNF rates were estimated using an isotope tracer method that overcame the
      uncertainty of the conventional bubble method by directly measuring the tracer
      enrichment during the incubations. Highest rates of BNF (~4 nM day-1) occurred in
      coastal surface waters and lowest detectable rates (~0.2 nM day-1) were found in
      the anoxic region of offshore stations. BNF was not detectable in most samples
      from oxygen-depleted waters. The composition of the N2-fixing assemblage was
      investigated by sequencing of nifH genes. The diazotrophic assemblage in surface
      waters contained mainly Proteobacterial sequences (Cluster I nifH), while both
      Proteobacterial sequences and sequences with high identities to those of
      anaerobic microbes characterized as Clusters III and IV type nifH sequences were
      found in the anoxic waters. Our results indicate modest input of N through BNF in
      oxygen-depleted zones mainly due to the activity of proteobacterial diazotrophs.

PMID- 28742074
TI  - Untargeted screening for novel autoantibodies with prognostic value in first
      episode psychosis.
AB  - Immunological and inflammatory reactions have been suggested to have a role in
      the development of schizophrenia, a hypothesis that has recently been supported
      by genetic data. The aim of our study was to perform an unbiased search for
      autoantibodies in patients with a first psychotic episode, and to explore the
      association between any seroreactivity and the development of a Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition (DSM-IV) disorder
      characterized by chronic or relapsing psychotic symptoms. We collected plasma
      samples from 53 patients when they were treated for their first-episode
      psychosis, and 41 non-psychotic controls, after which the patients were followed
      for a mean duration of 7 years. Thirty patients were diagnosed with
      schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder or
      a long-term unspecified nonorganic psychosis during follow-up, whereas 23
      patients achieved complete remission. At the end of follow-up, plasma samples
      were analyzed for IgG reactivity to 2304 fragments of human proteins using a
      multiplexed affinity proteomic technique. Eight patient samples showed
      autoreactivity to the N-terminal fragment of the PAGE (P antigen) protein family
      (PAGE2B/PAGE2/PAGE5), whereas no such autoreactivity was seen among the controls.
      PAGE autoreactivity was associated with a significantly increased risk of being
      diagnosed with schizophrenia during follow-up (odds ratio 6.7, relative risk
      4.6). An immunohistochemistry analysis using antisera raised against the N
      terminal fragment stained an unknown extracellular target in human cortical brain
      tissue. Our findings suggest that autoreactivity to the N-terminal portion of the
      PAGE protein family is associated with schizophrenia in a subset of patients with
      first-episode psychosis.

PMID- 28742075
TI  - Are individuals with higher psychopathic traits better learners at lying?
      Behavioural and neural evidence.
AB  - High psychopathy is characterized by untruthfulness and manipulativeness.
      However, existing evidence on higher propensity or capacity to lie among non
      incarcerated high-psychopathic individuals is equivocal. Of particular
      importance, no research has investigated whether greater psychopathic tendency is
      associated with better 'trainability' of lying. An understanding of whether the
      neurobehavioral processes of lying are modifiable through practice offers
      significant theoretical and practical implications. By employing a longitudinal
      design involving university students with varying degrees of psychopathic traits,
      we successfully demonstrate that the performance speed of lying about face
      familiarity significantly improved following two sessions of practice, which
      occurred only among those with higher, but not lower, levels of psychopathic
      traits. Furthermore, this behavioural improvement associated with higher
      psychopathic tendency was predicted by a reduction in lying-related neural
      signals and by functional connectivity changes in the frontoparietal and
      cerebellum networks. Our findings provide novel and pivotal evidence suggesting
      that psychopathic traits are the key modulating factors of the plasticity of both
      behavioural and neural processes underpinning lying. These findings broadly
      support conceptualization of high-functioning individuals with higher
      psychopathic traits as having preserved, or arguably superior, functioning in
      neural networks implicated in cognitive executive processing, but deficiencies in
      affective neural processes, from a neuroplasticity perspective.

PMID- 28742076
TI  - Altered neurite morphology and cholinergic function of induced pluripotent stem
      cell-derived neurons from a patient with Kleefstra syndrome and autism.
AB  - The aim of the present study was to establish an in vitro Kleefstra syndrome (KS)
      disease model using the human induced pluripotent stem cell (hiPSC) technology.
      Previously, an autism spectrum disorder (ASD) patient with Kleefstra syndrome (KS
      ASD) carrying a deleterious premature termination codon mutation in the EHMT1
      gene was identified. Patient specific hiPSCs generated from peripheral blood
      mononuclear cells of the KS-ASD patient were differentiated into post-mitotic
      cortical neurons. Lower levels of EHMT1 mRNA as well as protein expression were
      confirmed in these cells. Morphological analysis on neuronal cells differentiated
      from the KS-ASD patient-derived hiPSC clones showed significantly shorter
      neurites and reduced arborization compared to cells generated from healthy
      controls. Moreover, density of dendritic protrusions of neuronal cells derived
      from KS-ASD hiPSCs was lower than that of control cells. Synaptic connections and
      spontaneous neuronal activity measured by live cell calcium imaging could be
      detected after 5 weeks of differentiation, when KS-ASD cells exhibited higher
      sensitivity of calcium responses to acetylcholine stimulation indicating a lower
      nicotinic cholinergic tone at baseline condition in KS-ASD cells. In addition,
      gene expression profiling of differentiated neuronal cells from the KS-ASD
      patient revealed higher expression of proliferation-related genes and lower mRNA
      levels of genes involved in neuronal maturation and migration. Our data
      demonstrate anomalous neuronal morphology, functional activity and gene
      expression in KS-ASD patient-specific hiPSC-derived neuronal cultures, which
      offers an in vitro system that contributes to a better understanding of KS and
      potentially other neurodevelopmental disorders including ASD.

PMID- 28742077
TI  - Mediation by anxiety of the relationship between amygdala activity during emotion
      processing and poor quality of life in young adults.
AB  - Young adults often experience psychological distress and poor quality of life
      (QoL). Yet, there are no objective neural markers to accurately guide
      interventions to help improve these measures. We thus aimed to identify
      directional relationships between frontoamygdala emotional regulation circuitry
      activity during emotion processing, personality traits, and symptoms associated
      with psychological distress, and QoL. One hundred twenty 18-25-year olds, n=51
      psychologically distressed and n=69 healthy individuals, completed a face emotion
      processing task during functional magnetic resonance imaging, clinical and
      behavioral measures, and QoL assessment. Penalized regression, accounting for
      large numbers of independent variables, showed that increased state and trait
      anxiety, cohort and measures of general and anhedonic depression severity
      predicted poorer QoL (all exponents>0.87). Only state and trait anxiety predicted
      emotion processing-related frontoamygdala activity (all exponents=1.00). State
      and trait anxiety fully mediated the relationship between amygdala activity and
      QoL (P-value increased from 0.001 to 0.29: left amygdala, and from 0.003 to 0.94:
      right amygdala). State anxiety fully mediated the relationship between left
      ventrolateral prefrontal cortical (vlPFC) activity and QoL (P-value increased
      from 0.01 to 0.18). Testing an alternative mediational pathway showed that the
      relationship between state and trait anxiety and QoL was not mediated by amygdala
      or left vlPFC activity. We thereby identify specific, directional relationships
      linking amygdala and left vlPFC activity, state and trait anxiety, and poor QoL
      across different diagnoses. Our findings highlight roles of amygdala and left
      vlPFC activity as neural predictors of anxiety and poor QoL, and as potentially
      important targets for novel interventions to reduce anxiety and, in turn, improve
      QoL in young adults.

PMID- 28742078
TI  - Longitudinal changes in glucocorticoid receptor exon 1F methylation and
      psychopathology after military deployment.
AB  - Several cross-sectional studies have demonstrated the relevance of DNA
      methylation of the glucocorticoid receptor exon 1F region (GR-1F) for trauma
      related psychopathology. We conducted a longitudinal study to examine GR-1F
      methylation changes over time in relation to trauma exposure and the development
      of post-deployment psychopathology. GR-1F methylation (52 loci) was quantified
      using pyrosequencing in whole blood of 92 military men 1 month before and 6
      months after a 4-month deployment period to Afghanistan. GR-1F methylation
      overall (mean methylation and the number of methylated loci) and functional
      methylation (methylation at loci associated with GR exon 1F expression) measures
      were examined. We first investigated the effect of exposure to potentially
      traumatic events during deployment on these measures. Subsequently, changes in GR
      1F methylation were related to changes in mental health problems (total Symptom
      Checklist-90 score) and posttraumatic stress disorder (PTSD) symptoms (Self
      Report Inventory for PTSD). Trauma exposure during deployment was associated with
      an increase in all methylation measures, but development of mental health
      problems 6 months after deployment was only significantly associated with an
      increased functional methylation. Emergence of post-deployment PTSD symptoms was
      not related to increased functional methylation over time. Pre-deployment
      methylation levels did not predict post-deployment psychopathology. To our
      knowledge, this is the first study to prospectively demonstrate trauma-related
      increases in GR-1F methylation, and it shows that only increases at specific
      functionally relevant sites predispose for post-deployment psychopathology.

PMID- 28742079
TI  - The DCDC2 deletion is not a risk factor for dyslexia.
AB  - Dyslexia is a specific impairment in learning to read and has strong
      heritability. An intronic deletion within the DCDC2 gene, with ~8% frequency in
      European populations, is increasingly used as a marker for dyslexia in
      neuroimaging and behavioral studies. At a mechanistic level, this deletion has
      been proposed to influence sensory processing capacity, and in particular
      sensitivity to visual coherent motion. Our re-assessment of the literature,
      however, did not reveal strong support for a role of this specific deletion in
      dyslexia. We also analyzed data from five distinct cohorts, enriched for
      individuals with dyslexia, and did not identify any signal indicative of
      associations for the DCDC2 deletion with reading-related measures, including in a
      combined sample analysis (N=526). We believe we conducted the first replication
      analysis for a proposed deletion effect on visual motion perception and found no
      association (N=445 siblings). We also report that the DCDC2 deletion has a
      frequency of 37.6% in a cohort representative of the general population recruited
      in Hong Kong (N=220). This figure, together with a lack of association between
      the deletion and reading abilities in this cohort, indicates the low likelihood
      of a direct deletion effect on reading skills. Therefore, on the basis of
      multiple strands of evidence, we conclude that the DCDC2 deletion is not a strong
      risk factor for dyslexia. Our analyses and literature re-evaluation are important
      for interpreting current developments within multidisciplinary studies of
      dyslexia and, more generally, contribute to current discussions about the
      importance of reproducibility in science.

PMID- 28742080
TI  - Emergent, remitted and persistent psychosis-spectrum symptoms in 22q11.2 deletion
      syndrome.
AB  - Individuals with 22q11.2 deletion syndrome (22q11DS) are at markedly elevated
      risk for schizophrenia-related disorders. Stability, emergence, remission and
      persistence of psychosis-spectrum symptoms were investigated longitudinally.
      Demographic, clinical and cognitive predictors of psychosis were assessed.
      Prospective follow-up over 2.8 years was undertaken in 75 individuals with
      22q11DS aged 8-35 years. Mood, anxiety, attention-deficit hyperactivity disorders
      and psychosis-spectrum symptoms were assessed with the Kiddie-Schedule for
      Affective Disorders and Schizophrenia and Scale of Prodromal Symptoms (SOPS).
      Four domains of cognition were evaluated with the Penn Computerized
      Neurocognitive Battery (executive functioning, memory, complex cognition and
      social cognition). Psychotic disorder or clinically significant SOPS-positive
      ratings were consistently absent in 35%, emergent in 13%, remitted in 22% and
      persistent in 31% of participants. Negative symptoms and functional impairment
      were found to be predictive of the emergence of positive psychosis-spectrum
      symptoms and to reflect ongoing deficits after remission of positive symptoms.
      Dysphoric mood and anxiety were predictive of emergent and persistent-positive
      psychosis-spectrum symptoms. Lower baseline global cognition and greater global
      cognitive decline were predictive of psychosis-spectrum outcomes but no
      particular cognitive domain stood out as being significantly more discriminating
      than others. Our findings suggest that negative symptoms, functioning and
      dysphoric mood are important predictors of psychosis risk in this population.

PMID- 28742081
TI  - Serum fatty acid patterns in patients with schizophrenia: a targeted metabonomics
      study.
AB  - Previous studies have indicated that schizophrenia is linked to abnormal lipid
      metabolism. Free fatty acids (FFAs) in peripheral blood can reflect the status of
      lipid metabolism in human body. The purpose of this study was to scan the FFA
      pattern and elucidate the characteristics of lipid metabolic abnormality in
      schizophrenia patients. One hundred and ten patients with schizophrenia (SCZs)
      and 109 healthy controls (HCs) were included in the study and divided into a
      discovery set and a validation set. Forty-seven serum FFAs were detected by UPLC
      QTOF-MS and 39 of them were absolutely quantified by establishing standard
      curves. Monounsaturated fatty acids (MUFAs) and omega-6 polyunsaturated fatty
      acids (omega-6 PUFAs) were significantly increased in SCZs compared with HCs.
      Desaturation from saturated fatty acids to MUFAs and beta-oxidation were
      enhanced, as estimated by the ratios of products to precursors. These results
      suggest that lipolysis and beta-oxidation are upregulated in SCZ, presumably
      resulting from insufficient brain energy supply.

PMID- 28742082
TI  - Bacterial deception of MAIT cells in a cloud of superantigen and cytokines.
AB  - The bacterium Staphylococcus aureus is an important cause of the life-threatening
      condition toxic shock syndrome in humans. Bacterial toxins known as superantigens
      (SAgs) generate this illness by acting as broad activators of a substantial
      fraction of all T lymphocytes, bypassing the normally highly stringent T-cell
      receptor antigen specificity to cause a systemic inflammatory cytokine storm in
      the host. In a new study, Shaler et al. found that immune cells called mucosa
      associated invariant T (MAIT) cells make an unexpectedly large contribution to
      the SAg response in a largely T-cell receptor-independent, cytokine-driven
      manner. Subsequent to such activation, the MAIT cells remain unresponsive to
      stimulation with bacterial antigen. Thus, S. aureus hijacks MAIT cells in the
      cytokine storm and leaves them functionally impaired. This work provides new
      insight into the role of MAIT cells in antibacterial immunity and opens new
      avenues of investigation to understand and possibly treat bacterial toxic shock
      and sepsis.

PMID- 28742083
TI  - Long-time analytic approximation of large stochastic oscillators: Simulation,
      analysis and inference.
AB  - In order to analyse large complex stochastic dynamical models such as those
      studied in systems biology there is currently a great need for both analytical
      tools and also algorithms for accurate and fast simulation and estimation. We
      present a new stochastic approximation of biological oscillators that addresses
      these needs. Our method, called phase-corrected LNA (pcLNA) overcomes the main
      limitations of the standard Linear Noise Approximation (LNA) to remain uniformly
      accurate for long times, still maintaining the speed and analytically
      tractability of the LNA. As part of this, we develop analytical expressions for
      key probability distributions and associated quantities, such as the Fisher
      Information Matrix and Kullback-Leibler divergence and we introduce a new
      approach to system-global sensitivity analysis. We also present algorithms for
      statistical inference and for long-term simulation of oscillating systems that
      are shown to be as accurate but much faster than leaping algorithms and
      algorithms for integration of diffusion equations. Stochastic versions of
      published models of the circadian clock and NF-kappaB system are used to
      illustrate our results.

PMID- 28742084
TI  - Systematic tissue-specific functional annotation of the human genome highlights
      immune-related DNA elements for late-onset Alzheimer's disease.
AB  - Continuing efforts from large international consortia have made genome-wide
      epigenomic and transcriptomic annotation data publicly available for a variety of
      cell and tissue types. However, synthesis of these datasets into effective
      summary metrics to characterize the functional non-coding genome remains a
      challenge. Here, we present GenoSkyline-Plus, an extension of our previous work
      through integration of an expanded set of epigenomic and transcriptomic
      annotations to produce high-resolution, single tissue annotations. After
      validating our annotations with a catalog of tissue-specific non-coding elements
      previously identified in the literature, we apply our method using data from 127
      different cell and tissue types to present an atlas of heritability enrichment
      across 45 different GWAS traits. We show that broader organ system categories
      (e.g. immune system) increase statistical power in identifying biologically
      relevant tissue types for complex diseases while annotations of individual cell
      types (e.g. monocytes or B-cells) provide deeper insights into disease etiology.
      Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study
      of late-onset Alzheimer's disease (LOAD). Our analyses suggest a strong
      connection between LOAD heritability and genetic variants contained in regions of
      the genome functional in monocytes. Furthermore, we show that LOAD shares a
      similar localization of SNPs to monocyte-functional regions with Parkinson's
      disease. Overall, we demonstrate that integrated genome annotations at the single
      tissue level provide a valuable tool for understanding the etiology of complex
      human diseases. Our GenoSkyline-Plus annotations are freely available at
      http://genocanyon.med.yale.edu/GenoSkyline.

PMID- 28742086
TI  - Predictive models for estimating visceral fat: The contribution from
      anthropometric parameters.
AB  - BACKGROUND: Excessive adipose visceral tissue (AVT) represents an independent
      risk factor for cardiometabolic alterations. The search continues for a highly
      valid marker for estimating visceral adiposity that is a simple and low cost tool
      able to screen individuals who are highly at risk of being viscerally obese. The
      aim of this study was to develop a predictive model for estimating AVT volume
      using anthropometric parameters. OBJECTIVE: Excessive adipose visceral tissue
      (AVT) represents an independent risk factor for cardiometabolic alterations. The
      search continues for a highly valid marker for estimating visceral adiposity that
      is a simple and low cost tool able to screen individuals who are highly at risk
      of being viscerally obese. The aim of this study was to develop a predictive
      model for estimating AVT volume using anthropometric parameters. METHODS: A cross
      sectional study involving overweight individuals whose AVT was evaluated (using
      computed tomography-CT), along with the following anthropometric parameters: body
      mass index (BMI), abdominal circumference (AC), waist-to-hip ratio (WHpR), waist
      to-height ratio (WHtR), sagittal diameter (SD), conicity index (CI), neck
      circumference (NC), neck-to-thigh ratio (NTR), waist-to-thigh ratio (WTR), and
      body adiposity index (BAI). RESULTS: 109 individuals with an average age of
      50.3+/-12.2 were evaluated. The predictive equation developed to estimate AVT in
      men was AVT = -1647.75 +2.43(AC) +594.74(WHpR) +883.40(CI) (R2 adjusted: 64.1%).
      For women, the model chosen was: AVT = -634.73 +1.49(Age) +8.34(SD) + 291.51(CI)
      + 6.92(NC) (R2 adjusted: 40.4%). The predictive ability of the equations
      developed in relation to AVT volume determined by CT was 66.9% and 46.2% for
      males and females, respectively (p<0.001). CONCLUSIONS: A quick and precise AVT
      estimate, especially for men, can be obtained using only AC, WHpR, and CI for
      men, and age, SD, CI, and NC for women. These equations can be used as a clinical
      and epidemiological tool for overweight individuals.

PMID- 28742085
TI  - Clinically severe CACNA1A alleles affect synaptic function and neurodegeneration
      differentially.
AB  - Dominant mutations in CACNA1A, encoding the alpha-1A subunit of the neuronal P/Q
      type voltage-dependent Ca2+ channel, can cause diverse neurological phenotypes.
      Rare cases of markedly severe early onset developmental delay and congenital
      ataxia can be due to de novo CACNA1A missense alleles, with variants affecting
      the S4 transmembrane segments of the channel, some of which are reported to be
      loss-of-function. Exome sequencing in five individuals with severe early onset
      ataxia identified one novel variant (p.R1673P), in a girl with global
      developmental delay and progressive cerebellar atrophy, and a recurrent, de novo
      p.R1664Q variant, in four individuals with global developmental delay, hypotonia,
      and ophthalmologic abnormalities. Given the severity of these phenotypes we
      explored their functional impact in Drosophila. We previously generated null and
      partial loss-of-function alleles of cac, the homolog of CACNA1A in Drosophila.
      Here, we created transgenic wild type and mutant genomic rescue constructs with
      the two noted conserved point mutations. The p.R1673P mutant failed to rescue cac
      lethality, displayed a gain-of-function phenotype in electroretinograms (ERG)
      recorded from mutant clones, and evolved a neurodegenerative phenotype in aging
      flies, based on ERGs and transmission electron microscopy. In contrast, the
      p.R1664Q variant exhibited loss of function and failed to develop a
      neurodegenerative phenotype. Hence, the novel R1673P allele produces
      neurodegenerative phenotypes in flies and human, likely due to a toxic gain of
      function.

PMID- 28742087
TI  - Type 1-skewed neuroinflammation and vascular damage associated with Orientia
      tsutsugamushi infection in mice.
AB  - BACKGROUND: Scrub typhus is a life-threatening disease, due to infection with O.
      tsutsugamushi, a Gram-negative bacterium that preferentially replicates in
      endothelial cells and professional phagocytes. Meningoencephalitis has been
      reported in scrub typhus patients and experimentally-infected animals; however,
      the neurological manifestation and its underlying mechanisms remain poorly
      understood. To address this issue, we focused on Orientia tsutsugamushi Karp
      strain (OtK), and examined host responses in the brain during lethal versus self
      healing scrub typhus disease in our newly established murine models. PRINCIPLE
      FINDINGS: Following inoculation with a lethal dose of OtK, mice had a significant
      increase in brain transcripts related to pathogen-pattern recognition receptors
      (TLR2, TLR4, TLR9), type-1 responses (IFN-gamma, TNF-alpha, CXCL9, CXCR3), and
      endothelial stress/damage such as angiopoietins, but a rapid down-regulation of
      Tie2. Sublethal infection displayed similar trends, implying the development of
      type 1-skewed proinflammatory responses in infected brains, independent of time
      and disease outcomes. Focal hemorrhagic lesions and meningitis were evident in
      both infection groups, but pathological changes were more diffuse and frequent in
      lethal infection. At 6-10 days of lethal infection, the cortex and cerebellum
      sections had increased ICAM-1-positive staining in vascular cells, as well as
      increased detection of CD45+ leukocytes, CD3+ T cells, IBA1+ phagocytes, and
      GFAP+ astrocytes, but a marked loss of occludin-positive tight junction staining,
      implying progressive endothelial activation/damage and cellular recruitment in
      inflamed brains. Orientia were sparse in the brains, but readily detectable
      within lectin+ vascular and IBA-1+ phagocytic cells. These CNS alterations were
      consistent with type 1-skewed, IL-13-suppressed responses in lethally-infected
      mouse lungs. SIGNIFICANCE: This is the first report of type 1-skewed
      neuroinflammation and cellular activation, accompanied with vascular
      activation/damage, during OtK infection in C57BL/6 mice. This study not only
      enhances our understanding of the pathophysiological mechanisms of scrub typhus,
      but also correlates the impact of immune and vascular dysfunction on disease
      pathogenesis.

PMID- 28742089
TI  - A salient region detection model combining background distribution measure for
      indoor robots.
AB  - Vision system plays an important role in the field of indoor robot. Saliency
      detection methods, capturing regions that are perceived as important, are used to
      improve the performance of visual perception system. Most of state-of-the-art
      methods for saliency detection, performing outstandingly in natural images,
      cannot work in complicated indoor environment. Therefore, we propose a new method
      comprised of graph-based RGB-D segmentation, primary saliency measure, background
      distribution measure, and combination. Besides, region roundness is proposed to
      describe the compactness of a region to measure background distribution more
      robustly. To validate the proposed approach, eleven influential methods are
      compared on the DSD and ECSSD dataset. Moreover, we build a mobile robot platform
      for application in an actual environment, and design three different kinds of
      experimental constructions that are different viewpoints, illumination variations
      and partial occlusions. Experimental results demonstrate that our model
      outperforms existing methods and is useful for indoor mobile robots.

PMID- 28742088
TI  - Genome-wide identification of Hami melon miRNAs with putative roles during fruit
      development.
AB  - MicroRNAs represent a family of small endogenous, non-coding RNAs that play
      critical regulatory roles in plant growth, development, and environmental stress
      responses. Hami melon is famous for its attractive flavor and excellent
      nutritional value, however, the mechanisms underlying the fruit development and
      ripening remains largely unknown. Here, we performed small RNA sequencing to
      investigate the roles of miRNAs during Hami melon fruit development. Two batches
      of flesh samples were collected at four fruit development stages. Small RNA
      sequencing yielded a total of 54,553,424 raw reads from eight libraries. 113
      conserved miRNAs belonging to 30 miRNA families and nine novel miRNAs comprising
      nine miRNA families were identified. The expression of 42 conserved miRNAs and
      three Hami melon-specific miRNAs significantly changed during fruit development.
      Furthermore, 484 and 124 melon genes were predicted as putative targets of 29
      conserved and nine Hami melon-specific miRNA families, respectively. GO
      enrichment analysis were performed on target genes, "transcription, DNA
      dependent", "rRNA processing", "oxidation reduction", "signal transduction",
      "regulation of transcription, DNA-dependent", and "metabolic process" were the
      over-represented biological process terms. Cleavage sites of six target genes
      were validated using 5' RACE. Our results present a comprehensive set of
      identification and characterization of Hami melon fruit miRNAs and their
      potential targets, which provide valuable basis towards understanding the
      regulatory mechanisms in programmed process of normal Hami fruit development and
      ripening. Specific miRNAs could be selected for further research and applications
      in breeding practices.

PMID- 28742090
TI  - T-DNA-genome junctions form early after infection and are influenced by the
      chromatin state of the host genome.
AB  - Agrobacterium tumefaciens mediated T-DNA integration is a common tool for plant
      genome manipulation. However, there is controversy regarding whether T-DNA
      integration is biased towards genes or randomly distributed throughout the
      genome. In order to address this question, we performed high-throughput mapping
      of T-DNA-genome junctions obtained in the absence of selection at several time
      points after infection. T-DNA-genome junctions were detected as early as 6 hours
      post-infection. T-DNA distribution was apparently uniform throughout the
      chromosomes, yet local biases toward AT-rich motifs and T-DNA border sequence
      micro-homology were detected. Analysis of the epigenetic landscape of previously
      isolated sites of T-DNA integration in Kanamycin-selected transgenic plants
      showed an association with extremely low methylation and nucleosome occupancy.
      Conversely, non-selected junctions from this study showed no correlation with
      methylation and had chromatin marks, such as high nucleosome occupancy and high
      H3K27me3, that correspond to three-dimensional-interacting heterochromatin
      islands embedded within euchromatin. Such structures may play a role in capturing
      and silencing invading T-DNA.

PMID- 28742091
TI  - Multiple visual objects are sampled sequentially.
AB  - When acting in a complex visual environment, it is essential to be able to
      flexibly allocate attention to parts of the visual scene that may contain goal
      relevant information. The paper by Jia et al. provides novel evidence that our
      brains sequentially sample different objects in a visual scene. The results were
      obtained using "temporal response functions," in which unique
      electroencephalographic (EEG) signals corresponding to the processing of 2
      continuously presented objects were isolated in an object-specific way. These
      response functions were dominated by 10-Hz alpha-band activity. Crucially, the
      different objects were sequentially sampled at a rate of about 2 Hz. These
      findings provide important neurophysiological insights into how our visual system
      operates in complex environments.

PMID- 28742092
TI  - Cadmium exposure and endometrial cancer risk: A large midwestern U.S. population
      based case-control study.
AB  - Estrogen-mimicking chemicals, such as cadmium, may be associated with increased
      susceptibility to hormone-dependent cancers, though supporting data are sparse,
      particularly for endometrial cancer. The Health and Environmental Exposure
      Research (HEER) study worked with the Arkansas Central Cancer Registry, Iowa
      Cancer Registry and Missouri Cancer Registry to obtain names of women diagnosed
      with endometrial cancer who were willing to be contacted for participation in our
      case control study. Voter registration lists from Iowa and Missouri were used to
      randomly select similarly aged women as represented in the case population.
      Participants were interviewed by telephone to obtain information on known or
      suspected endometrial risk factors. Urine kits were sent to participants for home
      collection and returned for analysis. Our case-control study consisted of 631
      incident cases of endometrial cancer diagnosed from January 2010 to October 2012
      and 879 age-matched population-based controls, ages 18-81 years (mean age 65
      years). We quantified cadmium amounts in urine and standardized these values
      through creatinine adjustment. Using data from all survey completers, we
      developed a multivariable model for endometrial cancer. Creatinine-adjusted
      cadmium concentration was added to this model. Odds ratio (OR) and 95% confidence
      intervals (CIs) for endometrial cancer were calculated. After multivariable
      adjustment, higher creatinine-adjusted cadmium exposure was associated with a
      statistically significant increase of endometrial cancer risk (OR: 1.22; 95% CI:
      1.03-1.44). Our results provide evidence that cadmium may increase the risk of
      endometrial cancer, possibly through estrogenic effects.

PMID- 28742093
TI  - Neuronal synchrony and the relation between the blood-oxygen-level dependent
      response and the local field potential.
AB  - The most widespread measures of human brain activity are the blood-oxygen-level
      dependent (BOLD) signal and surface field potential. Prior studies report a
      variety of relationships between these signals. To develop an understanding of
      how to interpret these signals and the relationship between them, we developed a
      model of (a) neuronal population responses and (b) transformations from neuronal
      responses into the functional magnetic resonance imaging (fMRI) BOLD signal and
      electrocorticographic (ECoG) field potential. Rather than seeking a
      transformation between the two measures directly, this approach interprets each
      measure with respect to the underlying neuronal population responses. This model
      accounts for the relationship between BOLD and ECoG data from human visual cortex
      in V1, V2, and V3, with the model predictions and data matching in three ways:
      across stimuli, the BOLD amplitude and ECoG broadband power were positively
      correlated, the BOLD amplitude and alpha power (8-13 Hz) were negatively
      correlated, and the BOLD amplitude and narrowband gamma power (30-80 Hz) were
      uncorrelated. The two measures provide complementary information about human
      brain activity, and we infer that features of the field potential that are
      uncorrelated with BOLD arise largely from changes in synchrony, rather than
      level, of neuronal activity.

PMID- 28742094
TI  - Epidemiology, clinical features and risk factors for human rabies and animal
      bites during an outbreak of rabies in Maputo and Matola cities, Mozambique, 2014:
      Implications for public health interventions for rabies control.
AB  - BACKGROUND: In Mozambique, the majority of rabies outbreaks are unreported and
      data on the epidemiological features of human rabies and animal bites are scarce.
      An outbreak of human rabies in adjacent Maputo and Matola cities in 2014 prompted
      us to investigate the epidemiology, clinical features and risk factors of human
      rabies and animal bites in the two cities. METHODOLOGY/PRINCIPAL FINDINGS: We
      reviewed cases of human rabies and animal bites from April to July 2014, and
      carried out a community investigation in July and August in the neighborhoods
      where cases of human rabies resided. This investigation included collection of
      clinical, demographic and epidemiological information and a case control study to
      investigate the risk factors associated with human rabies. Fourteen cases of
      human rabies were detected in Maputo (n = 10) and Matola (n = 3) cities and
      neighbouring Boane district (n = 1) between April and August 2014, all of whom
      had been admitted to hospital. All had a recent history of dog bite. Of the 14
      rabid dogs, only one had been immunized. 819 cases of animal bites were
      registered, of which 64.6% (529/819) were from Maputo City. Dogs were responsible
      for 97.8% (801/819) of all animal bites, but only 27.0% (126/467) were immunized.
      Factors significantly associated with human rabies were: age <15 years (p =
      0.05), bite by stray dog (p = 0.002), deep wound (p = 0.02), bite in the head (p
      = 0.001), bite by unimmunized dog (p = 0.01), no use of soap and water (p =
      0.001), and no post-exposure prophylaxis (p = 0.01). CONCLUSIONS/SIGNIFICANCE:
      Implementation of control measures for rabies is poor in Maputo and Matola
      cities, where cases of human rabies were strongly associated with bites by stray
      and unvaccinated dogs and irregular implementation of post-exposure measures.

PMID- 28742095
TI  - Statistical process control applied to mechanized peanut sowing as a function of
      soil texture.
AB  - The successful establishment of agricultural crops depends on sowing quality,
      machinery performance, soil type and conditions, among other factors. This study
      evaluates the operational quality of mechanized peanut sowing in three soil types
      (sand, silt, and clay) with variable moisture contents. The experiment was
      conducted in three locations in the state of Sao Paulo, Brazil. The track
      sampling scheme was used for 80 sampling locations of each soil type. Descriptive
      statistics and statistical process control (SPC) were used to evaluate the
      quality indicators of mechanized peanut sowing. The variables had normal
      distributions and were stable from the viewpoint of SPC. The best performance for
      peanut sowing density, normal spacing, and the initial seedling growing stand was
      found for clayey soil followed by sandy soil and then silty soil. Sandy or clayey
      soils displayed similar results regarding sowing depth, which was deeper than in
      the silty soil. Overall, the texture and the moisture of clayey soil provided the
      best operational performance for mechanized peanut sowing.

PMID- 28742096
TI  - Insecticide resistance is mediated by multiple mechanisms in recently introduced
      Aedes aegypti from Madeira Island (Portugal).
AB  - BACKGROUND: Aedes aegypti is a major mosquito vector of arboviruses, including
      dengue, chikungunya and Zika. In 2005, Ae. aegypti was identified for the first
      time in Madeira Island. Despite an initial insecticide-based vector control
      program, the species expanded throughout the Southern coast of the island,
      suggesting the presence of insecticide resistance. Here, we characterized the
      insecticide resistance status and the underlying mechanisms of two populations of
      Ae. aegypti from Madeira Island, Funchal and Paul do Mar. METHODOLOGY/PRINCIPAL
      FINDINGS: WHO susceptibility bioassays indicated resistance to cyfluthrin,
      permethrin, fenitrothion and bendiocarb. Use of synergists significantly
      increased mortality rates, and biochemical assays indicated elevated activities
      of detoxification enzymes, suggesting the importance of metabolic resistance.
      Microarray-based transcriptome analysis detected significant upregulation in both
      populations of nine cytochrome P450 oxidase genes (including four known
      pyrethroid metabolizing enzymes), the organophosphate metabolizer CCEae3a,
      Glutathione-S-transferases, and multiple putative cuticle proteins. Genotyping of
      knockdown resistance loci linked to pyrethroid resistance revealed fixation of
      the 1534C mutation, and presence with moderate frequencies of the V1016I mutation
      in each population. CONCLUSIONS/SIGNIFICANCE: Significant resistance to three
      major insecticide classes (pyrethroid, carbamate and organophosphate) is present
      in Ae. aegypti from Madeira Island, and appears to be mediated by multiple
      mechanisms. Implementation of appropriate resistance management strategies
      including rotation of insecticides with alternative modes of action, and methods
      other than chemical-based vector control are strongly advised to delay or reverse
      the spread of resistance and achieve efficient control.

PMID- 28742097
TI  - MrTADFinder: A network modularity based approach to identify topologically
      associating domains in multiple resolutions.
AB  - Genome-wide proximity ligation based assays such as Hi-C have revealed that
      eukaryotic genomes are organized into structural units called topologically
      associating domains (TADs). From a visual examination of the chromosomal contact
      map, however, it is clear that the organization of the domains is not simple or
      obvious. Instead, TADs exhibit various length scales and, in many cases, a nested
      arrangement. Here, by exploiting the resemblance between TADs in a chromosomal
      contact map and densely connected modules in a network, we formulate TAD
      identification as a network optimization problem and propose an algorithm,
      MrTADFinder, to identify TADs from intra-chromosomal contact maps. MrTADFinder is
      based on the network-science concept of modularity. A key component of it is
      deriving an appropriate background model for contacts in a random chain, by
      numerically solving a set of matrix equations. The background model preserves the
      observed coverage of each genomic bin as well as the distance dependence of the
      contact frequency for any pair of bins exhibited by the empirical map. Also, by
      introducing a tunable resolution parameter, MrTADFinder provides a self
      consistent approach for identifying TADs at different length scales, hence the
      acronym "Mr" standing for Multiple Resolutions. We then apply MrTADFinder to
      various Hi-C datasets. The identified domain boundaries are marked by
      characteristic signatures in chromatin marks and transcription factors (TF) that
      are consistent with earlier work. Moreover, by calling TADs at different length
      scales, we observe that boundary signatures change with resolution, with
      different chromatin features having different characteristic length scales.
      Furthermore, we report an enrichment of HOT (high-occupancy target) regions near
      TAD boundaries and investigate the role of different TFs in determining
      boundaries at various resolutions. To further explore the interplay between TADs
      and epigenetic marks, as tumor mutational burden is known to be coupled to
      chromatin structure, we examine how somatic mutations are distributed across
      boundaries and find a clear stepwise pattern. Overall, MrTADFinder provides a
      novel computational framework to explore the multi-scale structures in Hi-C
      contact maps.

PMID- 28742099
TI  - Variants of ACAN are associated with severity of lumbar disc herniation in
      patients with chronic low back pain.
AB  - INTRODUCTION: Disc herniation is a complex spinal disorder associated with
      disability and high healthcare cost. Lumbar disc herniation is strongly
      associated with disc degeneration. Candidate genes of the aggrecan metabolic
      pathway may associate with the severity of lumbar disc herniation. OBJECTIVES:
      This study evaluated the association of single nucleotide variants (SNVs) of the
      candidate genes of the aggrecan metabolic pathway with the severity of lumbar
      disc herniation in patients with chronic mechanical low back pain. In addition,
      we assessed the in-silico functional analysis of the significant SNVs and
      association of their haplotypes with the severity of lumbar disc herniation.
      METHODS: A descriptive cross sectional study was carried out on 106 patients.
      Severity of disc herniation and disc degeneration were assessed on T2-weighted
      mid sagittal lumbar MRI scan. Sixty two exonic SNVs of ten candidate genes of
      aggrecan metabolic pathway (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1,
      TIMP2 and TIMP3) were genotyped on a Sequenom MassARRAY iPLEX platform.
      Multivariable linear regression analysis was carried out using PLINK 1.9 software
      adjusting for age, gender, body mass index and severity of disc degeneration.
      Four online bioinformatics tools (Provean, SIFT, PolyPhen and Mutation Taster)
      were used for in-silico functional analysis. RESULTS: Mean age was 52.42 +/- 9.42
      years and 69.8% were females. The mean severity of disc herniation was 2.81 +/-
      1.98. The rs2272023, rs35430524, rs2882676, rs2351491, rs938609, rs3825994,
      rs1042630, rs698621 and rs3817428 variants and their haplotypes of ACAN were
      associated with the severity of lumbar disc herniation. However, only the
      rs35430524, rs938609 and rs3817428 variants of ACAN were detected as pathogenic
      by in-silico functional analysis. CONCLUSIONS: SNVs of ACAN and their haplotypes
      are associated with the severity of lumbar disc herniation. Functional genetic
      studies are necessary to identify the role of these significant SNVs in the
      pathogenesis of disc herniation.

PMID- 28742098
TI  - Pathological manifestations in lymphatic filariasis correlate with lack of
      inhibitory properties of IgG4 antibodies on IgE-activated granulocytes.
AB  - Helminth parasites are known to be efficient modulators of their host's immune
      system. To guarantee their own survival, they induce alongside the classical Th2
      a strong regulatory response with high levels of anti-inflammatory cytokines and
      elevated plasma levels of IgG4. This particular antibody was shown in different
      models to exhibit immunosuppressive properties. How IgG4 affects the
      etiopathology of lymphatic filariasis (LF) is however not well characterized.
      Here we investigate the impact of plasma and affinity-purified IgG/IgG4 fractions
      from endemic normals (EN) and LF infected pathology patients (CP), asymptomatic
      microfilaraemic (Mf+) and amicrofilaraemic (Mf-) individuals on IgE/IL3 activated
      granulocytes. The activation and degranulation states were investigated by
      monitoring the expression of CD63/HLADR and the release of granule contents
      (neutrophil elastase (NE), eosinophil cationic protein (ECP) and histamine)
      respectively by flow cytometry and ELISA. We could show that the activation of
      granulocytes was inhibited in the presence of plasma from EN and Mf+ individuals
      whereas those of Mf- and CP presented no effect. This inhibitory capacity was
      impaired upon depletion of IgG in Mf+ individuals but persisted in IgG-depleted
      plasma from EN, where it strongly correlated with the expression of IgA. In
      addition, IgA-depleted fractions failed to suppress granulocyte activation.
      Strikingly, affinity-purified IgG4 antibodies from EN, Mf+ and Mf- individuals
      bound granulocytes and inhibited activation and the release of ECP, NE and
      histamine. In contrast, IgG4 from CP could not bind granulocytes and presented no
      suppressive capacity. Reduction of both the affinity to, and the suppressive
      properties of anti-inflammatory IgG4 on granulocytes was reached only when
      FcgammaRI and II were blocked simultaneously. These data indicate that IgG4
      antibodies from Mf+, Mf- and EN, in contrast to those of CP, natively exhibit
      FcgammaRI/II-dependent suppressive properties on granulocytes. Our findings
      suggest that quantitative and qualitative alterations in IgG4 molecules are
      associated with the different clinical phenotypes in LF endemic regions.

PMID- 28742100
TI  - A multifactor approach to forecasting Romanian gross domestic product (GDP) in
      the short run.
AB  - The purpose of this paper is to investigate the application of a generalized
      dynamic factor model (GDFM) based on dynamic principal components analysis to
      forecasting short-term economic growth in Romania. We have used a generalized
      principal components approach to estimate a dynamic model based on a dataset
      comprising 86 economic and non-economic variables that are linked to economic
      output. The model exploits the dynamic correlations between these variables and
      uses three common components that account for roughly 72% of the information
      contained in the original space. We show that it is possible to generate reliable
      forecasts of quarterly real gross domestic product (GDP) using just the common
      components while also assessing the contribution of the individual variables to
      the dynamics of real GDP. In order to assess the relative performance of the GDFM
      to standard models based on principal components analysis, we have also estimated
      two Stock-Watson (SW) models that were used to perform the same out-of-sample
      forecasts as the GDFM. The results indicate significantly better performance of
      the GDFM compared with the competing SW models, which empirically confirms our
      expectations that the GDFM produces more accurate forecasts when dealing with
      large datasets.

PMID- 28742101
TI  - Urban-rural differences in disability-free life expectancy in Bangladesh using
      the 2010 HIES data.
AB  - BACKGROUND: Research on health expectancy has been carried out in Bangladesh but
      none of it has examined the differences in Disability-Free Life Expectancy (DFLE)
      between urban and rural setting in context of rapid urbanization of Bangladesh in
      past decades. OBJECTIVES: The present study aims to estimate DFLE for people of
      all ages living in urban and rural areas in Bangladesh, and to examine the
      differences in DFLE between these two areas. METHODS: Data from the Sample Vital
      Registration System 2010 and the Bangladesh Household Income and Expenditure
      Survey (HIES) 2010 were used in this study. The Sullivan method was applied to
      estimate DFLE in Bangladesh. RESULTS: Higher rates of mortality and disability
      were observed in rural areas compared to urban areas with few exceptions.
      Statistically significant differences in DFLE were revealed from birth to age 15
      years for both sexes between urban and rural areas. Urban males had a longer life
      expectancy (LE), longer DFLE and shorter LE with disability both in number and
      proportion when compared to rural males. Rural females at age 20+ years had a
      longer LE than urban females but urban females had a longer DFLE and a shorter LE
      with disability in both number and proportion at all ages than did rural females.
      CONCLUSION: This study demonstrates that there were clear inequalities in LE,
      DFLE and LE with disability between rural and urban areas of Bangladesh along
      with age-specific differences as well. These findings may serve as useful and
      benchmark for intervention and policy implications for reducing the gap in health
      outcomes.

PMID- 28742102
TI  - Pancreatic size and fat content in diabetes: A systematic review and meta
      analysis of imaging studies.
AB  - OBJECTIVES: Imaging studies are expected to produce reliable information
      regarding the size and fat content of the pancreas. However, the available
      studies have produced inconclusive results. The aim of this study was to perform
      a systematic review and meta-analysis of imaging studies assessing pancreas size
      and fat content in patients with type 1 diabetes (T1DM) and type 2 diabetes
      (T2DM). METHODS: Medline and Embase databases were performed. Studies evaluating
      pancreatic size (diameter, area or volume) and/or fat content by ultrasound,
      computed tomography, or magnetic resonance imaging in patients with T1DM and/or
      T2DM as compared to healthy controls were selected. Seventeen studies including
      3,403 subjects (284 T1DM patients, 1,139 T2DM patients, and 1,980 control
      subjects) were selected for meta-analyses. Pancreas diameter, area, volume,
      density, and fat percentage were evaluated. RESULTS: Pancreatic volume was
      reduced in T1DM and T2DM vs. controls (T1DM vs. controls: -38.72 cm3, 95%CI: 
      52.25 to -25.19, I2 = 70.2%, p for heterogeneity = 0.018; and T2DM vs. controls: 
      12.18 cm3, 95%CI: -19.1 to -5.25, I2 = 79.3%, p for heterogeneity = 0.001). Fat
      content was higher in T2DM vs. controls (+2.73%, 95%CI 0.55 to 4.91, I2 = 82.0%,
      p for heterogeneity<0.001). CONCLUSIONS: Individuals with T1DM and T2DM have
      reduced pancreas size in comparison with control subjects. Patients with T2DM
      have increased pancreatic fat content.

PMID- 28742103
TI  - Impact of teachers training on HIV/AIDS education program among secondary school
      students in Bangladesh: A cross-sectional survey.
AB  - BACKGROUND: In 2007, the Government of Bangladesh incorporated a chapter on
      HIV/AIDS into the national curriculum for an HIV-prevention program for school
      students. For the efficient dissemination of knowledge, an intervention was
      designed to train the teachers and equip them to educate on the topic of
      HIV/AIDS. The present study intended to understand the impact of this
      intervention by assessing the knowledge, attitudes and behaviours related to
      HIV/AIDS, among the targeted students. METHODS: A cross-sectional survey was
      conducted with the students at randomly selected schools from two adjacent
      districts. Considering exposure to intervention, one district was assigned for
      intervention and the other as a control. In total, 1,381 students, aged 13-18
      years (or above) were interviewed, 675 from the control areas and 706 from the
      intervention areas. Univariate and bivariate analyses were performed on the
      collected data. RESULTS: A significantly higher proportion (p<0.001) of students
      in the intervention areas attended HIV/AIDS classes, demonstrated better
      knowledge and fewer misconceptions regarding the transmission and prevention of
      HIV. The same was derived regarding their attitude towards people living with
      HIV, as a higher proportion (p<0.001) responded positively, compared to the
      control groups of the study. Additionally, multinomial logistic regression
      analysis showed that students in intervention area were more likely to have good
      knowledge on HIV transmission (OR 2.71, 95% CI 1.74-4.22) and prevention (OR
      2.15, 95% CI 1.41-3.26) compared to the students in the control areas.
      CONCLUSIONS: The training programme needs to be scaled up, since it is likely to
      have an impact among students; we have witnessed that the interventions
      particularly helped increase HIV/AIDS knowledge among students and positively
      change the students' attitudes towards HIV/AIDS.

PMID- 28742104
TI  - Serum neutrophil gelatinase-associated lipocalin the estimation of hospital
      prognosis in patients with ST-elevated myocardial infarction.
AB  - We aimed to assess the clinical significance of serum levels of neutrophil
      gelatinase-associated lipocalin (sNGAL) for predicting in-hospital outcomes in
      patients with ST-elevated myocardial infarction (STEMI). Patients admitted within
      24 hours of developing STEMI clinical symptoms were evaluated for sNGAL on
      hospitalization days 1 and 12. Recurrent myocardial infarction, early post
      infarction angina, acute cerebrovascular accident, and death were assessed as
      adverse outcomes during hospitalization. The actors associated with adverse
      outcome were evaluated using univariate and multivariate regression analysis.
      Among the 260 STEMI patients included, 32% had >=1 adverse in-hospital outcome,
      and significantly higher sNGAL on day 12, (but not on day 1) compared to sNGAL in
      patients with favorable outcome (p = 0.033). Type-2 diabetes mellitus, age > 60
      years, reduced glomerular filtration rate during hospitalization, and high sNGAL
      on day 12 were identified as risk factors for adverse in-hospital outcome,
      associated with a 14% increase for each 1-year increment in age after 60 years,
      and a dramatic increase (3.2 times) for high sNGAL on day 12, with sNGAL >= 1.046
      ng/ml indicating complicated hospitalization course. sNGAL concentration on the
      12th day was associated with the existing adverse outcomes, acting as a marker of
      MI severity.

PMID- 28742105
TI  - Long-term risk of dementia after acute respiratory failure requiring intensive
      care unit admission.
AB  - This retrospective, population-based cohort study aims to investigate the long
      term risk of newly diagnosed dementia in patients discharged for acute
      respiratory failure that required mechanical ventilation (MV) and intensive care
      unit (ICU) admission. From the Taiwan National Health Insurance Research
      Database, first-time ICU patients using MV between June 1, 1998, and December 31,
      2012, were enrolled, and they were followed-up until the earliest onset of one of
      our two endpoints: a new diagnosis of dementia (primary endpoint), or the end of
      the study. A total of 18,033 patients were enrolled and thirteen hundred eighty
      seven patients had been newly diagnosed with dementia (mean onset: 3.2 years post
      discharge). Patients >= 85 years old had the highest risk (multivariate
      analysis). Males had a lower risk than did females in both models (HR: 0.81, 95%
      CI: 0.72-0.9 in model 1; HR: 0.80, 95% CI: 0.72-0.89 in model 2). ICU stays > 5
      days, hospital stays > 14 days, and more ICU readmissions were associated with a
      higher risk of developing dementia. In conclusion, the long-term risks of a
      subsequent diagnosis of dementia for acute respiratory failure with MV patients
      who survive to discharge increase with age and are higher in women than in men.
      Additionally, the longer the ICU or hospital stay is, and the more ICU
      readmissions a patient has, are both significantly associated with developing
      dementia.

PMID- 28742106
TI  - Epidemiology of enteroaggregative Escherichia coli infections and associated
      outcomes in the MAL-ED birth cohort.
AB  - BACKGROUND: Enteroaggregative E. coli (EAEC) have been associated with mildly
      inflammatory diarrhea in outbreaks and in travelers and have been increasingly
      recognized as enteric pathogens in young children with and without overt
      diarrhea. We examined the risk factors for EAEC infections and their associations
      with environmental enteropathy biomarkers and growth outcomes over the first two
      years of life in eight low-resource settings of the MAL-ED study. METHODS: EAEC
      infections were detected by PCR gene probes for aatA and aaiC virulence traits in
      27,094 non-diarrheal surveillance stools and 7,692 diarrheal stools from 2,092
      children in the MAL-ED birth cohort. We identified risk factors for EAEC and
      estimated the associations of EAEC with diarrhea, enteropathy biomarker
      concentrations, and both short-term (one to three months) and long-term (to two
      years of age) growth. RESULTS: Overall, 9,581 samples (27.5%) were positive for
      EAEC, and almost all children had at least one detection (94.8%) by two years of
      age. Exclusive breastfeeding, higher enrollment weight, and macrolide use within
      the preceding 15 days were protective. Although not associated with diarrhea,
      EAEC infections were weakly associated with biomarkers of intestinal inflammation
      and more strongly with reduced length at two years of age (LAZ difference
      associated with high frequency of EAEC detections: -0.30, 95% CI: -0.44, -0.16).
      CONCLUSIONS: Asymptomatic EAEC infections were common early in life and were
      associated with linear growth shortfalls. Associations with intestinal
      inflammation were small in magnitude, but suggest a pathway for the growth
      impact. Increasing the duration of exclusive breastfeeding may help prevent these
      potentially inflammatory infections and reduce the long-term impact of early
      exposure to EAEC.

PMID- 28742107
TI  - Analyzing the locomotory gaitprint of Caenorhabditis elegans on the basis of
      empirical mode decomposition.
AB  - The locomotory gait analysis of the microswimmer, Caenorhabditis elegans, is a
      commonly adopted approach for strain recognition and examination of phenotypic
      defects. Gait is also a visible behavioral expression of worms under external
      stimuli. This study developed an adaptive data analysis method based on empirical
      mode decomposition (EMD) to reveal the biological cues behind intricate motion.
      The method was used to classify the strains of worms according to their
      gaitprints (i.e., phenotypic traits of locomotion). First, a norm of the
      locomotory pattern was created from the worm of interest. The body curvature of
      the worm was decomposed into four intrinsic mode functions (IMFs). A radar chart
      showing correlations between the predefined database and measured worm was then
      obtained by dividing each IMF into three parts, namely, head, mid-body, and tail.
      A comprehensive resemblance score was estimated after k-means clustering.
      Simulated data that use sinusoidal waves were generated to assess the feasibility
      of the algorithm. Results suggested that temporal frequency is the major factor
      in the process. In practice, five worm strains, including wild-type N2, TJ356
      (zIs356), CL2070 (dvIs70), CB0061 (dpy-5), and CL2120 (dvIs14), were
      investigated. The overall classification accuracy of the gaitprint analyses of
      all the strains reached nearly 89%. The method can also be extended to classify
      some motor neuron-related locomotory defects of C. elegans in the same fashion.

PMID- 28742108
TI  - Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.
AB  - A crucial role of cell metabolism in immune cell differentiation and function has
      been recently established. Growing evidence indicates that metabolic processes
      impact both, innate and adaptive immunity. Since a down-stream integrator of
      metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for
      controlling the balance between pro-inflammatory interleukin (IL)-12 and anti
      inflammatory IL-10, we investigated the effect of upstream interference using
      metabolic modulators on the production of pro- and anti-inflammatory cytokines.
      Cytokine release and protein expression in human and murine myeloid cells was
      assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co
      treatment with 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK)
      activators. Additionally, the impact of metabolic interference was analysed in an
      in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased
      the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently
      inhibited the release of anti-inflammatory IL-10. Similar effects have been
      observed using pharmacological AMPK activation. Consistently, an inhibition of
      the tuberous sclerosis complex-mTOR pathway was observed. In line with our in
      vitro observations, glycolysis inhibition with 2-DG showed significantly reduced
      bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In
      conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine
      balance, establishing novel targets for metabolism-based immune-modulation.

PMID- 28742109
TI  - Young Sprague Dawley rats infected by Plasmodium berghei: A relevant experimental
      model to study cerebral malaria.
AB  - Cerebral malaria (CM) is the most severe manifestation of human malaria yet is
      still poorly understood. Mouse models have been developed to address the subject.
      However, their relevance to mimic human pathogenesis is largely debated. Here we
      study an alternative cerebral malaria model with an experimental Plasmodium
      berghei Keyberg 173 (K173) infection in Sprague Dawley rats. As in Human, not all
      infected subjects showed cerebral malaria, with 45% of the rats exhibiting
      Experimental Cerebral Malaria (ECM) symptoms while the majority (55%) of the
      remaining rats developed severe anemia and hyperparasitemia (NoECM). These
      results allow, within the same population, a comparison of the noxious effects of
      the infection between ECM and severe malaria without ECM. Among the ECM rats,
      77.8% died between day 5 and day 12 post-infection, while the remaining rats were
      spontaneously cured of neurological signs within 24-48 hours. The clinical ECM
      signs observed were paresis quickly evolving to limb paralysis, global paralysis
      associated with respiratory distress, and coma. The red blood cell (RBC) count
      remained normal but a drastic decrease of platelet count and an increase of white
      blood cell numbers were noted. ECM rats also showed a decrease of glucose and
      total CO2 levels and an increase of creatinine levels compared to control rats or
      rats with no ECM. Assessment of the blood-brain barrier revealed loss of
      integrity, and interestingly histopathological analysis highlighted cyto
      adherence and sequestration of infected RBCs in brain vessels from ECM rats only.
      Overall, this ECM rat model showed numerous clinical and histopathological
      features similar to Human CM and appears to be a promising model to achieve
      further understanding the CM pathophysiology in Humans and to evaluate the
      activity of specific antimalarial drugs in avoiding/limiting cerebral damages
      from malaria.

PMID- 28742110
TI  - Evaluation of exome variants using the Ion Proton Platform to sequence error
      prone regions.
AB  - The Ion Proton sequencer from Thermo Fisher accurately determines sequence
      variants from target regions with a rapid turnaround time at a low cost. However,
      misleading variant-calling errors can occur. We performed a systematic evaluation
      and manual curation of read-level alignments for the 675 ultrarare variants
      reported by the Ion Proton sequencer from 27 whole-exome sequencing data but that
      are not present in either the 1000 Genomes Project and the Exome Aggregation
      Consortium. We classified positive variant calls into 393 highly likely false
      positives, 126 likely false positives, and 156 likely true positives, which
      comprised 58.2%, 18.7%, and 23.1% of the variants, respectively. We identified
      four distinct error patterns of variant calling that may be bioinformatically
      corrected when using different strategies: simplicity region, SNV cluster,
      peripheral sequence read, and base inversion. Local de novo assembly successfully
      corrected 201 (38.7%) of the 519 highly likely or likely false positives. We also
      demonstrate that the two sequencing kits from Thermo Fisher (the Ion PI
      Sequencing 200 kit V3 and the Ion PI Hi-Q kit) exhibit different error profiles
      across different error types. A refined calling algorithm with better polymerase
      may improve the performance of the Ion Proton sequencing platform.

PMID- 28742111
TI  - Axonal outgrowth, neuropeptides expression and receptors tyrosine kinase
      phosphorylation in 3D organotypic cultures of adult dorsal root ganglia.
AB  - Limited knowledge from mechanistic studies on adult sensory neuronal activity was
      generated, to some extent, in recapitulated adult in vivo 3D microenvironment. To
      fill this gap there is a real need to better characterize the adult dorsal root
      ganglia (aDRG) organotypic cultures to make these in vitro systems exploitable
      for different approaches, ranging from basic neurobiology to regenerative
      therapies, to address the sensory nervous system in adult stage. We conducted a
      direct head-to-head comparison of aDRG and embryonic DRG (eDRG) organotypic
      culture focusing on axonal growth, neuropeptides expression and receptors
      tyrosine kinase (RTK) activation associated with neuronal survival, proliferation
      and differentiation. To identify alterations related to culture conditions, these
      parameters were also addressed in retrieved aDRG and eDRG and compared with
      organotypic cultures. Under similar neurotrophic stimulation, aDRG organotypic
      cultures displayed lower axonal outgrowth rate supported by reduced expression of
      growth associated protein-43 and high levels of RhoA and glycogen synthase kinase
      3 beta mRNA transcripts. In addition, differential alteration in sensory
      neuropeptides expression, namely calcitonin gene-related peptide and substance P,
      was detected and was mainly pronounced at gene expression levels. Among 39
      different RTK, five receptors from three RTK families were emphasized:
      tropomyosin receptor kinase A (TrkA), epidermal growth factor receptors (EGFR,
      ErbB2 and ErbB3) and platelet-derived growth factor receptor (PDGFR). Of note,
      except for EGFR, the phosphorylation of these receptors was dependent on DRG
      developmental stage and/or culture condition. In addition, EGFR and PDGFR
      displayed alterations in their cellular expression pattern in cultured DRG.
      Overall we provided valuable information particularly important when addressing
      in vitro the molecular mechanisms associated with development, maturation and
      regeneration of the sensory nervous system.

PMID- 28742112
TI  - Energy cost of isolated resistance exercises across low- to high-intensities.
AB  - This study aimed to estimate the energy cost across various intensities at eight
      popular resistance exercises: half squat, 45 degrees  inclined leg press, leg
      extension, horizontal bench press, 45 degrees  inclined bench press, lat pull
      down, triceps extension and biceps curl. 58 males (27.5 +/- 4.9 years, 1.78 +/-
      0.06 m height, 78.67 +/- 10.7 kg body mass and 11.4 +/- 4.1% estimated body fat)
      were randomly divided into four groups of 14 subjects each. For each group, two
      exercises were randomly assigned and on different days, they performed four bouts
      of 5-min constant-intensity for each of the two assigned exercises: 12%, 16%, 20%
      and 24% 1-RM. Later, the subjects performed exhaustive bouts at 80% 1-RM in the
      same two exercises. The mean values of VO2 at the last 30s of exercise at 12, 16,
      20 and 24% 1-RM bouts were plotted against relative intensity (% 1-RM) in a
      simple linear regression mode. The regressions were then used to predict O2
      demand for the higher intensity (80% 1-RM). Energy cost rose linearly with
      exercise intensity in every exercise with the lowest mean values were found in
      biceps curl and the highest in half squat exercise (p<0.001). Half squat exercise
      presented significant (p<0.001) higher values of energy cost in all intensities,
      when compared with the remaining exercises. This study revealed that low
      intensity resistance exercise provides energy cost comprised between 3 and 10
      kcal?min-1. Energy cost rose past 20 kcal?min-1 at 80% 1-RM in leg exercise. In
      addition, at 80% 1-RM, it was found that upper body exercises are less anaerobic
      than lower-body exercises.

PMID- 28742113
TI  - Addition of 17-(allylamino)-17-demethoxygeldanamycin to a suboptimal caspofungin
      treatment regimen in neutropenic rats with invasive pulmonary aspergillosis
      delays the time to death but does not enhance the overall therapeutic efficacy.
AB  - Caspofungin (CAS) which is used as salvage therapy in patients with invasive
      pulmonary aspergillosis (IPA) inhibits the 1,3-beta-D-glucan synthesis in
      Aspergillus fumigatus. Inhibiting 1,3-beta-D-glucan synthesis induces a stress
      response and in an invertebrate model it was demonstrated that inhibiting this
      response with geldamycin enhanced the therapeutic efficacy of CAS. Since
      geldamycin itself is toxic to mammalians, the therapeutic efficacy of combining
      geldamycin with CAS was not studied in rodent models. Therefore in this study we
      investigated if the geldamycin derivate 17-(allylamino)-17-demethoxygeldanamycin
      (17-AAG) was able to enhance the therapeutic efficacy of CAS in vitro and in our
      IPA model in transiently neutropenic rats. In vitro we confirmed the earlier
      demonstrated synergy between 17-AAG and CAS in ten A. fumigatus isolates. In vivo
      we treated A. fumigatus infected neutropenic rats with a sub-optimal dose of 0.75
      mg/kg/day CAS and 1 mg/kg/day 17-AAG for ten days. Survival was monitored for 21
      days after fungal inoculation. It appeared that the addition 17-AAG delayed death
      but did not improve overall survival of rats with IPA. Increasing the doses of 17
      AAG was not possible due to hepatic toxicity. This study underlines the need to
      develop less toxic and more fungal specific geldamycin derivatives and the need
      to test such drugs not only in invertebrate models but also in mammalian models.

PMID- 28742114
TI  - A unique polysaccharide purified from Hericium erinaceus mycelium prevents
      oxidative stress induced by H2O2 in human gastric mucosa epithelium cell.
AB  - Hericium erinaceus (HE) has been used both as a traditional Chinese medicine and
      home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a
      purified polysaccharide isolated from HE mycelium, has recently been identified
      as the active component responsible for HE anti-gastritis activity. Because
      oxidative stress has been implicated as a pathogenic cause of gastritis and
      gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro
      using the human gastric mucosal epithelial cell line, GES-1. Results showed that
      EP-1 possessed higher oxygen radical absorbance capacity (ORAC) and 2-3 times
      higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide and
      hydroxyl radicals than a hot water extract of commercially available HE fruiting
      body. A crude mycelial polysaccharide (CMPS) extract of HE, from which EP-1 was
      purified, showed slightly stronger radical scavenging activity and ORAC than EP
      1, with the exception of DPPH-scavenging activity. Antioxidant activities of
      these extracts were further studied using hydrogen peroxide (H2O2)-abused GES-1
      cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed
      via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced
      apoptotic cell death by inhibiting activation of apoptotic cellular signals
      within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2
      induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS
      exhibited comparable or stronger in vitro antioxidant activity than did EP-1.

PMID- 28742115
TI  - Mind wandering during attention performance: Effects of ADHD-inattention
      symptomatology, negative mood, ruminative response style and working memory
      capacity.
AB  - OBJECTIVE: In adulthood, depressive mood is often comorbid with ADHD, but its
      role in ADHD-inattentiveness and especially relations with mind wandering remains
      to be elucidated. This study investigated the effects of laboratory-induced
      dysphoric mood on task-unrelated mind wandering and its consequences on cognitive
      task performance in college students with high (n = 46) or low (n = 44) ADHD
      Inattention symptomatology and Hyperactivity/Impulsivity symptoms in the normal
      range. METHODS: These non-clinical high/low ADHD-Inattention symptom groups
      underwent negative or positive mood induction after which mind wandering
      frequency was measured in a sustained attention (SART), and a reading task.
      Effects of ruminative response style and working memory capacity on mind
      wandering frequency were also investigated. RESULTS: Significantly higher
      frequencies of self -reported mind wandering in daily life, in the SART and
      reading task were reported in the ADHD-Inattention symptom group, with
      detrimental effects on text comprehension in the reading task. Induced dysphoric
      mood did specifically enhance the frequency of mind wandering in the ADHD
      Inattention symptom group only during the SART, and was related to their higher
      self-reported intrusive ruminative response styles. Working memory capacity did
      not differ between high/low attention groups and did not influence any of the
      reported effects. CONCLUSIONS: These combined results suggest that in a non
      clinical sample with high ADHD-inattention symptoms, dysphoric mood and a
      ruminative response style seem to be more important determinants of dysfunctional
      mind wandering than a failure in working memory capacity/executive control, and
      perhaps need other ways of remediation, like cognitive behavioral therapy or
      mindfulness training.

PMID- 28742116
TI  - Sutureless microvascular anastomosis assisted by an expandable shape-memory alloy
      stent.
AB  - Vascular anastomosis is the highlight of cardiovascular, transplant, and
      reconstructive surgery, which has long been performed by hand using a needle and
      suture. However, anastomotic thrombosis occurs in approximately 0.5-10% of cases,
      which can cause serious complications. To improve the surgical outcomes, attempts
      to develop devices for vascular anastomosis have been made, but they have had
      limitations in handling, cost, patency rate, and strength at the anastomotic
      site. Recently, indwelling metal stents have been greatly improved with precise
      laser metalwork through programming technology. In the present study, we designed
      a bare metal stent, Microstent, that was constructed by laser machining of a
      shape-memory alloy, NiTi. An end-to-end microvascular anastomosis was performed
      in SD rats by placing the Microstent at the anastomotic site and gluing the
      junction. The operation time for the anastomosis was significantly shortened
      using Microstent. Thrombus formation, patency rate, and blood vessel strength in
      the Microstent anastomosis were superior or comparable to hand-sewn anastomosis.
      The results demonstrated the safety and effectiveness, as well as the
      operability, of the new method, suggesting its great benefit for surgeons by
      simplifying the technique for microvascular anastomosis.

PMID- 28742117
TI  - Comparison of GCaMP3 and GCaMP6f for studying astrocyte Ca2+ dynamics in the
      awake mouse brain.
AB  - In recent years it has become increasingly clear that astrocytes play a much more
      active role in neural processes than the traditional view of them as supporting
      cells suggests. Although not electrically excitable, astrocytes exhibit diverse
      Ca2+ dynamics across spatial and temporal scales, more or less dependent on the
      animal's behavioral state. Ca2+ dynamics range from global elevations lasting
      multiple seconds encompassing the soma up to the finest processes, to short
      elevations restricted to so-called microdomains within fine processes.
      Investigations of astrocyte Ca2+ dynamics have particularly benefitted from the
      development of Genetically-Encoded Calcium Indicators (GECIs). GECI expression
      can be achieved non-invasively in a cell type-specific manner and it can be
      genetically targeted to subcellular domains. The GCaMP family, a group of GECIs
      derived from the green fluorescent protein, has experienced some of the fastest
      advancements during the past decade. As a consequence we are now facing the
      challenge of needing to compare published data obtained with different versions
      of GECIs. With the intention to provide some guidance, here we compared Ca2+
      dynamics across scales in awake transgenic mice expressing either the well
      established GCaMP3, or the increasingly popular GCaMP6f, specifically in
      astrocytes. We found that locomotion-induced global Ca2+ elevations in cortical
      astrocytes displayed only minor kinetic differences and their apparent dynamic
      ranges for Ca2+ sensing were not different. In contrast, Ca2+ waves in processes
      and microdomain Ca2+ transients were much more readily detectable with GCaMP6f.
      Our findings suggest that behavioral state-dependent global astrocyte Ca2+
      responses can be studied with either GCaMP3 or GCaMP6f whereas the latter is more
      appropriate for studies of spatially restricted weak and fast Ca2+ dynamics.

PMID- 28742118
TI  - Similarities and differences between on-scalp and conventional in-helmet
      magnetoencephalography recordings.
AB  - The development of new magnetic sensor technologies that promise sensitivities
      approaching that of conventional MEG technology while operating at far lower
      operating temperatures has catalysed the growing field of on-scalp MEG. The
      feasibility of on-scalp MEG has been demonstrated via benchmarking of new sensor
      technologies performing neuromagnetic recordings in close proximity to the head
      surface against state-of-the-art in-helmet MEG sensor technology. However,
      earlier work has provided little information about how these two approaches
      compare, or about the reliability of observed differences. Herein, we present
      such a comparison, based on recordings of the N20m component of the somatosensory
      evoked field as elicited by electric median nerve stimulation. As expected from
      the proximity differences between the on-scalp and in-helmet sensors, the
      magnitude of the N20m activation as recorded with the on-scalp sensor was higher
      than that of the in-helmet sensors. The dipole pattern of the on-scalp recordings
      was also more spatially confined than that of the conventional recordings. Our
      results furthermore revealed unexpected temporal differences in the peak of the
      N20m component. An analysis protocol was therefore developed for assessing the
      reliability of this observed difference. We used this protocol to examine our
      findings in terms of differences in sensor sensitivity between the two types of
      MEG recordings. The measurements and subsequent analysis raised attention to the
      fact that great care has to be taken in measuring the field close to the zero
      line crossing of the dipolar field, since it is heavily dependent on the
      orientation of sensors. Taken together, our findings provide reliable evidence
      that on-scalp and in-helmet sensors measure neural sources in mostly similar
      ways.

PMID- 28742119
TI  - DoEstRare: A statistical test to identify local enrichments in rare genomic
      variants associated with disease.
AB  - Next-generation sequencing technologies made it possible to assay the effect of
      rare variants on complex diseases. As an extension of the "common disease-common
      variant" paradigm, rare variant studies are necessary to get a more complete
      insight into the genetic architecture of human traits. Association studies of
      these rare variations show new challenges in terms of statistical analysis. Due
      to their low frequency, rare variants must be tested by groups. This approach is
      then hindered by the fact that an unknown proportion of the variants could be
      neutral. The risk level of a rare variation may be determined by its impact but
      also by its position in the protein sequence. More generally, the molecular
      mechanisms underlying the disease architecture may involve specific protein
      domains or inter-genic regulatory regions. While a large variety of methods are
      optimizing functionality weights for each single marker, few evaluate variant
      position differences between cases and controls. Here, we propose a test called
      DoEstRare, which aims to simultaneously detect clusters of disease risk variants
      and global allele frequency differences in genomic regions. This test estimates,
      for cases and controls, variant position densities in the genetic region by a
      kernel method, weighted by a function of allele frequencies. We compared
      DoEstRare with previously published strategies through simulation studies as well
      as re-analysis of real datasets. Based on simulation under various scenarios,
      DoEstRare was the sole to consistently show highest performance, in terms of type
      I error and power both when variants were clustered or not. DoEstRare was also
      applied to Brugada syndrome and early-onset Alzheimer's disease data and provided
      complementary results to other existing tests. DoEstRare, by integrating variant
      position information, gives new opportunities to explain disease susceptibility.
      DoEstRare is implemented in a user-friendly R package.

PMID- 28742120
TI  - Virus-induced asthma attack: The importance of allergic inflammation in response
      to viral antigen in an animal model of asthma.
AB  - Asthma exacerbation can be a life-threatening condition, and is most often
      triggered by common respiratory viruses. Poor asthma control and worsening of
      respiratory function is associated with increased airway inflammation, including
      eosinophilia. Prevention of asthma exacerbation relies on treatment with
      corticosteroids, which preferentially inhibit allergic inflammation like
      eosinophils. Human studies demonstrate that inactivated virus can trigger
      eosinophil activation in vitro through antigen presentation and memory CD4+
      lymphocytes. We hypothesized that animals with immunologic memory to a
      respiratory virus would also develop airway hyperresponsiveness in response to a
      UV-inactivated form of the virus if they have pre-existing allergic airway
      inflammation. Guinea pigs were ovalbumin-sensitized, infected with live
      parainfluenza virus (PIV), aerosol-challenged with ovalbumin, and then re
      inoculated 60 days later with live or UV-inactivated PIV. Some animals were
      either treated with dexamethasone prior to the second viral exposure. Lymphocytes
      were isolated from parabronchial lymph nodes to confirm immunologic memory to the
      virus. Airway reactivity was measured and inflammation was assessed using
      bronchoalveolar lavage and lung histology. The induction of viral immunologic
      memory was confirmed in infected animals. Allergen sensitized and challenged
      animals developed airway hyperreactivity with eosinophilic airway inflammation
      when re-exposed to UV-inactivated PIV, while non-sensitized animals did not.
      Airway hyperreactivity in the sensitized animals was inhibited by pre-treatment
      with dexamethasone. We suggest that the response of allergic inflammation to
      virus antigen is a significant factor causing asthma exacerbation. We propose
      that this is one mechanism explaining how corticosteroids prevent virus-induced
      asthma attack.

PMID- 28742121
TI  - Correction: Relationship of mechanical impact magnitude to neurologic dysfunction
      severity in a rat traumatic brain injury model.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178186.].

PMID- 28742122
TI  - Main predictors of periphyton species richness depend on adherence strategy and
      cell size.
AB  - Periphytic algae are important components of aquatic ecosystems. However, the
      factors driving periphyton species richness variation remain largely unexplored.
      Here, we used data from a subtropical floodplain (Upper Parana River floodplain,
      Brazil) to quantify the influence of environmental variables (total suspended
      matter, temperature, conductivity, nutrient concentrations, hydrology,
      phytoplankton biomass, phytoplankton species richness, aquatic macrophyte species
      richness and zooplankton density) on overall periphytic algal species richness
      and on the richness of different algal groups defined by morphological traits
      (cell size and adherence strategy). We expected that the coefficients of
      determination of the models estimated for different trait-based groups would be
      higher than the model coefficient of determination of the entire algal community.
      We also expected that the relative importance of explanatory variables in
      predicting species richness would differ among algal groups. The coefficient of
      determination for the model used to predict overall periphytic algal species
      richness was higher than the ones obtained for models used to predict the species
      richness of the different groups. Thus, our first prediction was not supported.
      Species richness of aquatic macrophytes was the main predictor of periphyton
      species richness of the entire community and a significant predictor of the
      species richness of small mobile, large mobile and small-loosely attached algae.
      Abiotic variables, phytoplankton species richness, chlorophyll-a concentration,
      and hydrology were also significant predictors, depending on the group. These
      results suggest that habitat heterogeneity (as proxied by aquatic macrophytes
      richness) is important for maintaining periphyton species richness in floodplain
      environments. However, other factors played a role, suggesting that the analysis
      of species richness of different trait-based groups unveils relationships that
      were not detectable when the entire community was analysed together.

PMID- 28742123
TI  - Molecular and MALDI-TOF identification of ticks and tick-associated bacteria in
      Mali.
AB  - Ticks are considered the second vector of human and animal diseases after
      mosquitoes. Therefore, identification of ticks and associated pathogens is an
      important step in the management of these vectors. In recent years, Matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) has been reported as a promising method for the identification of arthropods
      including ticks. The objective of this study was to improve the conditions for
      the preparation of tick samples for their identification by MALDI-TOF MS from
      field-collected ethanol-stored Malian samples and to evaluate the capacity of
      this technology to distinguish infected and uninfected ticks. A total of 1,333
      ticks were collected from mammals in three distinct sites from Mali.
      Morphological identification allowed classification of ticks into 6 species
      including Amblyomma variegatum, Hyalomma truncatum, Hyalomma marginatum rufipes,
      Rhipicephalus (Boophilus) microplus, Rhipicephalus evertsi evertsi and
      Rhipicephalus sanguineus sl. Among those, 471 ticks were randomly selected for
      molecular and proteomic analyses. Tick legs submitted to MALDI-TOF MS revealed a
      concordant morpho/molecular identification of 99.6%. The inclusion in our MALDI
      TOF MS arthropod database of MS reference spectra from ethanol-preserved tick leg
      specimens was required to obtain reliable identification. When tested by
      molecular tools, 76.6%, 37.6%, 20.8% and 1.1% of the specimens tested were
      positive for Rickettsia spp., Coxiella burnetii, Anaplasmataceae and Borrelia
      spp., respectively. These results support the fact that MALDI-TOF is a reliable
      tool for the identification of ticks conserved in alcohol and enhances knowledge
      about the diversity of tick species and pathogens transmitted by ticks
      circulating in Mali.

PMID- 28742124
TI  - Correction: Assessing the facilitators and barriers of interdisciplinary team
      working in primary care using normalisation process theory: An integrative
      review.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0177026.].

PMID- 28742125
TI  - Y chromosomal evidence on the origin of northern Thai people.
AB  - The Khon Mueang represent the major group of people present in today's northern
      Thailand. While linguistic and genetic data seem to support a shared ancestry
      between Khon Mueang and other Tai-Kadai speaking people, the possibility of an
      admixed origin with contribution from local Mon-Khmer population could not be
      ruled out. Previous studies conducted on northern Thai people did not provide a
      definitive answer and, in addition, have largely overlooked the distribution of
      paternal lineages in the area. In this work we aim to provide a comprehensive
      analysis of Y paternal lineages in northern Thailand and to explicitly model the
      origin of the Khon Mueang population. We obtained and analysed new Y chromosomal
      haplogroup data from more than 500 northern Thai individuals including Khon
      Mueang, Mon-Khmer and Tai-Kadai. We also explicitly simulated different
      demographic scenarios, developed to explain the Khon Mueang origin, employing an
      ABC simulation framework on both mitochondrial and Y microsatellites data. Our
      results highlighted a similar haplogroup composition of Khon Mueang and Tai-Kadai
      populations in northern Thailand, with shared high frequencies of haplogroups O
      PK4, O-M117 and O-M111. Our ABC simulations also favoured a model in which the
      ancestors of modern Khon Mueang originated recently after a split from the other
      Tai-Kadai populations. Our different analyses concluded that the ancestors of
      Khon Mueang are likely to have originated from the same source of the other Tai
      Kadai groups in southern China, with subsequent admixture events involving native
      Mon-Khmer speakers restricted to some specific populations.

PMID- 28742126
TI  - The pre-Columbian introduction and dispersal of Algarrobo (Prosopis, Section
      Algarobia) in the Atacama Desert of northern Chile.
AB  - Archaeological and palaeoecological studies throughout the Americas have
      documented widespread landscape and environmental transformation during the pre
      Columbian era. The highly dynamic Formative (or Neolithic) period in northern
      Chile (ca. 3700-1550 yr BP) brought about the local establishment of agriculture,
      introduction of new crops (maize, quinoa, manioc, beans, etc.) along with a major
      population increase, new emergent villages and technological innovations. Even
      trees such as the Algarrobos (Prosopis section Algarobia) may have been part of
      this transformation. Here, we provide evidence that these species were not native
      to the Atacama Desert of Chile (18-27 degrees S), appearing only in the late
      Holocene and most likely due to human actions. We assembled a database composed
      of 41 taxon specific AMS radiocarbon dates from archaeobotanical and
      palaeoecological records (rodent middens, leaf litter deposits), as well an
      extensive bibliographical review comprising archaeobotanical, paleoecological,
      phylogenetic and taxonomic data to evaluate the chronology of introduction and
      dispersal of these trees. Although Algarrobos could have appeared as early as
      4200 yr BP in northernmost Chile, they only became common throughout the Atacama
      over a thousand years later, during and after the Formative period. Cultural and
      natural factors likely contributed to its spread and consolidation as a major
      silvicultural resource.

PMID- 28742127
TI  - Tpc1 is an important Zn(II)2Cys6 transcriptional regulator required for polarized
      growth and virulence in the rice blast fungus.
AB  - The establishment of polarity is a critical process in pathogenic fungi,
      mediating infection-related morphogenesis and host tissue invasion. Here, we
      report the identification of TPC1 (Transcription factor for Polarity Control 1),
      which regulates invasive polarized growth in the rice blast fungus Magnaporthe
      oryzae. TPC1 encodes a putative transcription factor of the fungal Zn(II)2Cys6
      family, exclusive to filamentous fungi. Tpc1-deficient mutants show severe
      defects in conidiogenesis, infection-associated autophagy, glycogen and lipid
      metabolism, and plant tissue colonisation. By tracking actin-binding proteins,
      septin-5 and autophagosome components, we show that Tpc1 regulates cytoskeletal
      dynamics and infection-associated autophagy during appressorium-mediated plant
      penetration. We found that Tpc1 interacts with Mst12 and modulates its DNA
      binding activity, while Tpc1 nuclear localisation also depends on the MAP kinase
      Pmk1, consistent with the involvement of Tpc1 in this signalling pathway, which
      is critical for appressorium development. Importantly, Tpc1 directly regulates
      NOXD expression, the p22phox subunit of the fungal NADPH oxidase complex via an
      interaction with Mst12. Tpc1 therefore controls spatial and temporal regulation
      of cortical F-actin through regulation of the NADPH oxidase complex during
      appressorium re-polarisation. Consequently, Tpc1 is a core developmental
      regulator in filamentous fungi, linking the regulated synthesis of reactive
      oxygen species and the Pmk1 pathway, with polarity control during host invasion.

PMID- 28742128
TI  - Construction and characterization of the Korean whole saliva proteome to
      determine ethnic differences in human saliva proteome.
AB  - As the first step to discover protein disease biomarkers from saliva, global
      analyses of the saliva proteome have been carried out since the early 2000s, and
      more than 3,000 proteins have been identified in human saliva. Recently, ethnic
      differences in the human plasma proteome have been reported, but such
      corresponding studies on human saliva in this aspect have not been previously
      reported. Thus, here, in order to determine ethnic differences in the human
      saliva proteome, a Korean whole saliva (WS) proteome catalogue indexing 480
      proteins was built and characterized through nLC-Q-IMS-TOF analyses of WS samples
      collected from eleven healthy South Korean male adult volunteers for the first
      time. Identification of 226 distinct Korean WS proteins, not observed in the
      integrated human saliva protein dataset, and significant gene ontology
      distribution differences in the Korean WS proteome compared to the integrated
      human saliva proteome strongly support ethnic differences in the human saliva
      proteome. Additionally, the potential value of ethnicity-specific human saliva
      proteins as biomarkers for diseases highly prevalent in that ethnic group was
      confirmed by finding 35 distinct Korean WS proteins likely to be associated with
      the top 10 deadliest diseases in South Korea. Finally, the present Korean WS
      protein list can serve as the first level reference for future proteomic studies
      including disease biomarker studies on Korean saliva.

PMID- 28742129
TI  - Treatment outcomes of pre-surgical infant orthopedics in patients with non
      syndromic cleft lip and/or palate: A systematic review and meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Non-syndromic clefts lip and/or palate (CL/P) defects may have
      manifold significant and detrimental consequences for the affected individuals
      and their family environment. Although the use of pre-surgical infant orthopedics
      (PSIO) was introduced as a means to improve management and treatment outcomes,
      there still remains a controversy. OBJECTIVE: To investigate the effectiveness of
      PSIO in patients with non-syndromic CL/P and evaluate the quality of the
      available evidence. SEARCH METHODS: Search without restrictions, together with
      hand searching, until May 2016. SELECTION CRITERIA: Randomized clinical trials
      investigating the effects of pre-surgical infant orthopedic appliances. DATA
      COLLECTION AND ANALYSIS: Following study retrieval and selection, data extraction
      and individual study risk of bias assessment using the Cochrane Risk of Bias Tool
      took place. The overall quality of the available evidence was assessed with the
      Grades of Recommendation, Assessment, Development and Evaluation approach.
      RESULTS: Finally 20 papers (3 unique trials) were identified, involving a total
      of 118 patients with unilateral complete CL/P and 16 with cleft of the soft and
      at least two thirds of the hard palate. Eight publications were considered as
      being of low, four of unclear and eight of high risk of bias. In general, the
      investigated appliances did not present significant effects when compared to each
      other or to no treatment in terms of feeding and general body growth, facial
      esthetics, cephalometric variables, maxillary dentoalveolar variables and dental
      arch relationships, speech and language evaluation, caregiver-reported outcomes,
      economic evaluation, as well as, adverse effects and problems. Overall, the
      quality of the available evidence was considered low. CONCLUSIONS: The
      aforementioned findings could provide initial guidance in the clinical setting.
      However, given the multitude of parameters, which may have affected the results,
      good practice would suggest further research, in order to reach more robust
      relevant recommendations for management decisions in individual cases.

PMID- 28742130
TI  - Association between complicated liver cirrhosis and the risk of hepatocellular
      carcinoma in Taiwan.
AB  - Hepatic encephalopathy, ascites, and variceal bleeding are the three major
      complications of cirrhosis. It is well known that cirrhosis is the most important
      risk factor of hepatocellular carcinoma (HCC). However, little is known about
      whether the severity of liver cirrhosis has an effect on the incidence of HCC.
      This population-based cohort study aimed to explore the association between
      complicated cirrhosis and HCC, and identify the risk factors of HCC in patients
      with complicated cirrhosis. Data of the years 1997-2011 were extracted from the
      National Health Insurance Research Database of Taiwan. A total of 2568 patients
      with complicated cirrhosis without HCC at baseline were enrolled. After
      propensity score matching, another 2568 patients with non-complicated cirrhosis
      were included. Hazards Cox regression analysis by using a competing risk
      regression model to control for possible confounding factors was utilized to
      estimate the association of the complications of liver cirrhosis with the risk of
      HCC. We observed by using competing risk analysis that the adjusted hazard ratio
      (HR) for developing HCC during the follow-up period after the initial
      hospitalization was higher among the patients with baseline complicated cirrhosis
      than in those with uncomplicated cirrhosis (HR, 1.23; 95% confidence interval,
      CI, 1.10-1.37, p<0.001). Additionally, older patients (HR, 1.01; 95% CI, 1.01
      1.02, p<0.001), males (HR, 0.84; 95% CI, 0.74-0.96, p = 0.009), and patients with
      alcohol-related cirrhosis (HR, 1.93; 95% CI, 1.65-2.26, p<0.001) had a
      statistically significant difference in the incidence of HCC. In conclusion,
      complicated liver cirrhosis is associated with a higher risk of HCC in Taiwan
      compared with cirrhosis without complications.

PMID- 28742132
TI  - Theory and development of biplanar active shim coils for a permanent NMR
      analyzer.
AB  - The general expression for magnetic induction in the z axis direction is derived
      from magnetic scalar potential, and magnetic induction for biplanar shimming
      coils (BSCs) is also derived from magnetic vector potentials and Green functions,
      which simultaneously include Sin and Cos harmonic fields. The relationship
      between these expressions is discussed, and we show they are partially
      consistent. Magnetic induction generated Sin and Cos stream functions, which are
      presented and discussed, and we conclude that the type of stream function
      determines the type of harmonic field, and that BSCs can not only generate
      specific harmonic fields directly using Cos stream function, but also generate
      the rest of the harmonic fields through some specific operations. The detailed
      design process is presented in the form of a diagram. Subsequently, nine BSCs
      were calculated using the proposed method and applied to a low field NMR
      relaxation analyzer. The magnetic field homogeneity after shimming increases
      significantly, which verifies its practical value.

PMID- 28742131
TI  - Biochemical characterization and comparison of aspartylglucosaminidases secreted
      in venom of the parasitoid wasps Asobara tabida and Leptopilina heterotoma.
AB  - Aspartylglucosaminidase (AGA) is a low-abundance intracellular enzyme that plays
      a key role in the last stage of glycoproteins degradation, and whose deficiency
      leads to human aspartylglucosaminuria, a lysosomal storage disease. Surprisingly,
      high amounts of AGA-like proteins are secreted in the venom of two
      phylogenetically distant hymenopteran parasitoid wasp species, Asobara tabida
      (Braconidae) and Leptopilina heterotoma (Cynipidae). These venom AGAs have a
      similar domain organization as mammalian AGAs. They share with them key residues
      for autocatalysis and activity, and the mature alpha- and beta-subunits also form
      an (alphabeta)2 structure in solution. Interestingly, only one of these AGAs
      subunits (alpha for AtAGA and beta for LhAGA) is glycosylated instead of the two
      subunits for lysosomal human AGA (hAGA), and these glycosylations are partially
      resistant to PGNase F treatment. The two venom AGAs are secreted as fully
      activated enzymes, they have a similar aspartylglucosaminidase activity and are
      both also efficient asparaginases. Once AGAs are injected into the larvae of the
      Drosophila melanogaster host, the asparaginase activity may play a role in
      modulating their physiology. Altogether, our data provide new elements for a
      better understanding of the secretion and the role of venom AGAs as virulence
      factors in the parasitoid wasps' success.

PMID- 28742133
TI  - A putative ATP/GTP binding protein affects Leishmania mexicana growth in insect
      vectors and vertebrate hosts.
AB  - BACKGROUND: Leishmania virulence factors responsible for the complicated
      epidemiology of the various leishmaniases remain mainly unidentified. This study
      is a characterization of a gene previously identified as upregulated in two of
      three overlapping datasets containing putative factors important for Leishmania's
      ability to establish mammalian intracellular infection and to colonize the gut of
      an insect vector. METHODOLOGY/PRINCIPAL FINDINGS: The investigated gene encodes
      ATP/GTP binding motif-containing protein related to Leishmania development 1
      (ALD1), a cytosolic protein that contains a cryptic ATP/GTP binding P-loop. We
      compared differentiation, growth rates, and infective abilities of wild-type and
      ALD1 null mutant cell lines of L. mexicana. Loss of ALD1 results in retarded
      growth kinetics but not defects in differentiation in axenic culture. Similarly,
      when mice and the sand fly vector were infected with the ALD1 null mutant, the
      primary difference in infection and colonization phenotype relative to wild type
      was an inability to achieve maximal host pathogenicity. While ability of the ALD1
      null mutant cells to infect macrophages in vitro was not affected, replication
      within macrophages was clearly curtailed. CONCLUSIONS/SIGNIFICANCE: L. mexicana
      ALD1, encoding a protein with no assigned functional domains or motifs, was
      identified utilizing multiple comparative analyses with the related and often
      experimentally overlooked monoxenous flagellates. We found that it plays a role
      in Leishmania infection and colonization in vitro and in vivo. Results suggest
      that ALD1 functions in L. mexicana's general metabolic network, rather than
      function in specific aspect of virulence as anticipated from the compared
      datasets. This result validates our comparative genomics approach for finding
      relevant factors, yet highlights the importance of quality laboratory-based
      analysis of genes tagged by these methods.

PMID- 28742134
TI  - Hemostasis pad combined with compression device after transradial coronary
      procedures: A randomized controlled trial.
AB  - BACKGROUND: Arterial access and hemostasis are important processes during
      percutaneous coronary procedures. In this study, we tested if the use of chitosan
      based pads on top of compression devices could improve hemostasis efficacy
      compared with compression devices alone after transradial coronary angiography or
      interventions. METHODS: This study was a single-center open-label randomized
      controlled trial. Patients who underwent coronary angiography or intervention
      with the transradial approach were randomly assigned to the study (compression
      device and a chitosan-based pad) or control (compression devices alone) group in
      a 2:1 fashion. The primary endpoint was time to hemostasis, categorized into <=5,
      6-10, 11-20, and >20 minutes. RESULTS: Between April and July 2016, 95 patients
      were enrolled (59 were assigned to the study arm and 36 to the control arm). Time
      to hemostasis, the primary endpoint, was significantly lower in the study group
      than in the control group (p<0.001). Both groups showed low rates of vascular
      complications. CONCLUSIONS: This study suggests that the use of a hemostasis pad
      in combination with rotatory compression devices is a safe and effective
      hemostasis strategy after radial artery access. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02954029.

PMID- 28742135
TI  - Salmonella enterica serovar-specific transcriptional reprogramming of infected
      cells.
AB  - Despite their high degree of genomic similarity, different Salmonella enterica
      serovars are often associated with very different clinical presentations. In
      humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid
      fever, a life-threatening systemic disease. In contrast, the non-typhoidal S.
      enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular
      bases for these different clinical presentations are incompletely understood. The
      ability to re-program gene expression in host cells is an essential virulence
      factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have
      compared the transcriptional profile of cultured epithelial cells infected with
      S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct
      transcriptional responses in infected cells that are associated with the
      stimulation of specific signal transduction pathways. These specific responses
      were associated with the presence of a distinct repertoire of type III secretion
      effector proteins. These observations provide major insight into the molecular
      bases for potential differences in the pathogenic mechanisms of typhoidal and non
      typhoidal S. enterica serovars.

PMID- 28742136
TI  - Can a tablet-based cancellation test identify cognitive impairment in older
      adults?
AB  - BACKGROUND AND OBJECTIVE: There has been a growing interest in using computerized
      cognitive assessment to detect age-related cognitive disorders. We have developed
      a tablet-based cancellation test (e-CT), previously shown as a reliable measure
      of executive functions and free of effect of familiarity with computer-based
      devices in healthy older adults. This study aimed to investigate the influence of
      demographics and current daily use of computer-based devices in older adults with
      Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). We further studied
      the ability of the e-CT to discriminate MCI and AD patients from older adults
      with normal cognition (NC). METHODS: The e-CT was administered to 325 older
      adults (NC = 112, MCI = 129, AD = 84). Subjects also performed the K-T test, a
      paper-and-pencil cancellation test from which the e-CT was developed. Multiple
      linear regression analyses were conducted to assess the contribution of
      demographics and current daily use of computer-based devices on the e-CT in
      patient groups. The Receiver Operating Characteristic (ROC) curves and the Area
      Under the Curve (AUC) were established to compare the efficacy of the e-CT and
      the K-T test to classify subjects into diagnostic groups. RESULTS: In the MCI
      group, age (B = -0.37, p<0.001) and current daily use of computer-based devices
      (B = 5.85, p<0.001) were associated with the number of correct cancellations of
      the e-CT. In the AD group, only current daily use of a computer-based device was
      a significant contributor (B = 6.28, p<0.001). The e-CT (AUC = 0.811; 95%
      confidence interval [CI]: 0.756-0.867) and the K-T (AUC = 0.837; CI: 0.787-0.887)
      showed good and comparable diagnostic accuracy to discriminate between MCI and NC
      subjects. To discriminate between NC and AD, both tests showed high diagnostic
      accuracy, with the AUC values of 0.923 (CI: 0.876-0.971) and 0.929 (95%CI: 0.886
      0.972) for the e-CT and the K-T, respectively. CONCLUSION: The e-CT presents
      satisfying discriminative validity and is a promising tool for detection of early
      cognitive impairment in older adults.

PMID- 28742137
TI  - Water immersion decreases sympathetic skin response during color-word Stroop
      test.
AB  - Water immersion alters the autonomic nervous system (ANS) response in humans. The
      effect of water immersion on executive function and ANS responses related to
      executive function tasks was unknown. Therefore, this study aimed to determine
      whether water immersion alters ANS response during executive tasks. Fourteen
      healthy participants performed color-word-matching Stroop tasks before and after
      non-immersion and water immersion intervention for 15 min in separate sessions.
      The Stroop task-related skin conductance response (SCR) was measured during every
      task. In addition, the skin conductance level (SCL) and electrocardiograph
      signals were measured over the course of the experimental procedure. The main
      findings of the present study were as follows: 1) water immersion decreased the
      executive task-related sympathetic nervous response, but did not affect executive
      function as evaluated by Stroop tasks, and 2) decreased SCL induced by water
      immersion was maintained for at least 15 min after water immersion. In
      conclusion, the present results suggest that water immersion decreases the
      sympathetic skin response during the color-word Stroop test without altering
      executive performance.

PMID- 28742138
TI  - Long-term prognostic factors of chronic central serous chorioretinopathy after
      half-dose photodynamic therapy: A 3-year follow-up study.
AB  - PURPOSE: To evaluate the long-term efficacy and factors involved in the
      recurrence and persistence of subretinal fluid (SRF) after half-dose photodynamic
      therapy (PDT) for chronic central serous chorioretinopathy (CSC). METHODS: In
      this retrospective observational case series, 79 eyes (73 patients) with chronic
      CSC were treated with half-dose PDT and followed up for at least 3 years. They
      were divided into successful (64 eyes) and unsuccessful (15 eyes) groups based on
      SRF absorption and disease recurrence after one PDT session. Age, best-corrected
      visual acuity (BCVA), central foveal thickness, neuroretinal thickness, height of
      SRF, subfoveal choroidal thickness, window defect area detected by fluorescein
      angiography, and PDT spot area were compared between the groups. Factors
      associated with PDT success and BCVA at 3 years were investigated. RESULTS:
      LogMAR BCVA improved from 0.21+/-0.24 to 0.08+/-0.16 (P<0.001) at 3 years after
      PDT. Compared with the unsuccessful group, the successful group had a
      significantly younger mean age (50.5+/-9.7 vs. 56.5+/-9.1 years, P = 0.032) and
      better baseline BCVA (0.18+/-0.23 vs. 0.32+/-0.25, P = 0.034). Other parameters
      were not significantly different. Multivariate analyses showed that unsuccessful
      PDT was significantly associated with lower baseline BCVA (P = 0.026) and older
      age (P = 0.029) and that BCVA at 3 years after PDT was positively associated with
      baseline BCVA (P<0.001). CONCLUSIONS: Half-dose PDT has a long-term efficacy in
      chronic CSC. Relatively early PDT may improve anatomic and functional outcomes of
      chronic CSC.

PMID- 28742139
TI  - Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8
      results in C2 and C4 consumption away from the bacterial surface.
AB  - Whooping cough, or pertussis, is a contagious disease of the respiratory tract
      that is re-emerging worldwide despite high vaccination coverage. The causative
      agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on
      complement evasion strategies of this pathogen is limited. However, this is of
      great importance for future vaccine development as it has become apparent that a
      novel pertussis vaccine is needed. Here, we unravel the effect of Virulence
      associated gene 8 (Vag8) of B. pertussis on the human complement system at the
      molecular level. We show that both recombinant and endogenously secreted Vag8
      inhibit complement deposition on the bacterial surface at the level of C4b. We
      reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the
      binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active
      proteases that subsequently cleave C2 and C4 away from the bacterial surface. We
      demonstrate that the depletion of these complement components in the bacterial
      surrounding and subsequent decreased deposition on B. pertussis leads to less
      complement-mediated bacterial killing. Vag8 is the first protein described that
      specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates
      complement consumption away from the bacterial surface. Unravelling the mechanism
      of this unique complement evasion strategy of B. pertussis is one of the first
      steps towards understanding the interactions between the first line of defense
      complement and B. pertussis.

PMID- 28742140
TI  - Short (16-mer) locked nucleic acid splice-switching oligonucleotides restore
      dystrophin production in Duchenne Muscular Dystrophy myotubes.
AB  - Splice-switching antisense oligonucleotides (SSOs) offer great potential for RNA
      targeting therapies, and two SSO drugs have been recently approved for treating
      Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA). Despite
      promising results, new developments are still needed for more efficient
      chemistries and delivery systems. Locked nucleic acid (LNA) is a chemically
      modified nucleic acid that presents several attractive properties, such as high
      melting temperature when bound to RNA, potent biological activity, high stability
      and low toxicity in vivo. Here, we designed a series of LNA-based SSOs
      complementary to two sequences of the human dystrophin exon 51 that are most
      evolutionary conserved and evaluated their ability to induce exon skipping upon
      transfection into myoblasts derived from a DMD patient. We show that 16-mers with
      60% of LNA modification efficiently induce exon skipping and restore synthesis of
      a truncated dystrophin isoform that localizes to the plasma membrane of patient
      derived myotubes differentiated in culture. In sum, this study underscores the
      value of short LNA-modified SSOs for therapeutic applications.

PMID- 28742141
TI  - Bruton's tyrosine kinase inhibitor BMS-986142 in experimental models of
      rheumatoid arthritis enhances efficacy of agents representing clinical standard
      of-care.
AB  - Bruton's tyrosine kinase (BTK) regulates critical signal transduction pathways
      involved in the pathobiology of rheumatoid arthritis (RA) and other autoimmune
      disorders. BMS-986142 is a potent and highly selective reversible small molecule
      inhibitor of BTK currently being investigated in clinical trials for the
      treatment of both RA and primary Sjogren's syndrome. In the present report, we
      detail the in vitro and in vivo pharmacology of BMS-986142 and show this agent
      provides potent and selective inhibition of BTK (IC50 = 0.5 nM), blocks antigen
      receptor-dependent signaling and functional endpoints (cytokine production, co
      stimulatory molecule expression, and proliferation) in human B cells (IC50 <= 5
      nM), inhibits Fcgamma receptor-dependent cytokine production from peripheral
      blood mononuclear cells, and blocks RANK-L-induced osteoclastogenesis. Through
      the benefits of impacting these important drivers of autoimmunity, BMS-986142
      demonstrated robust efficacy in murine models of rheumatoid arthritis (RA),
      including collagen-induced arthritis (CIA) and collagen antibody-induced
      arthritis (CAIA). In both models, robust efficacy was observed without
      continuous, complete inhibition of BTK. When a suboptimal dose of BMS-986142 was
      combined with other agents representing the current standard of care for RA
      (e.g., methotrexate, the TNFalpha antagonist etanercept, or the murine form of
      CTLA4-Ig) in the CIA model, improved efficacy compared to either agent alone was
      observed. The results suggest BMS-986142 represents a potential therapeutic for
      clinical investigation in RA, as monotherapy or co-administered with agents with
      complementary mechanisms of action.

PMID- 28742142
TI  - Effects of water drinking test on ocular blood flow waveform parameters: A laser
      speckle flowgraphy study.
AB  - The water-drinking test (WDT) is a provocative test used in glaucoma research to
      assess the effects of elevated intraocular pressure (IOP). Defective
      autoregulation due to changes in perfusion pressure may play a role in the
      pathophysiology of several ocular diseases. This study aims to examine the
      effects of WDT on ocular blood flow (in the form of pulse waveform parameters
      obtained using laser speckle flowgraphy) to gain insight into the physiology of
      ocular blood flow and its autoregulation in healthy individuals. Changes in pulse
      waveform parameters of mean blur rate (MBR) in the entire optic nerve head (ONH),
      the vasculature of the ONH, the tissue area of the ONH, and the avascular tissue
      area located outside of the ONH were monitored over time. Significant increases
      in the falling rate of MBR over the entire ONH and its tissue area and decreases
      in blowout time (BOT) of the tissue area were observed only at 10 minutes after
      water intake. Significant increases in the skew of the waveform and the falling
      rate were observed in the vasculature of the ONH at 40 and 50 minutes after water
      intake, respectively. In the avascular region of the choroid, the average MBR
      increased significantly up to 30 minutes after water intake. Furthermore, the
      rising rate in this region increased significantly at 20 and 40 minutes, and the
      falling rate and acceleration-time index were both significantly increased at 40
      minutes after water intake. Our results indicate the presence of effective
      autoregulation of blood flow at the ONH after WDT. However, in the choroidal
      region, outside of the ONH, effective autoregulation was not observed until 30
      minutes after water intake in healthy study participants. These pulse waveform
      parameters could potentially be used in the diagnosis and/or monitoring of
      patients with glaucoma.

PMID- 28742143
TI  - Impact of rapid identification of positive blood cultures using the Verigene
      system on antibiotic prescriptions: A prospective study of community-onset
      bacteremia in a tertiary hospital in Japan.
AB  - BACKGROUND: Rapid identification of positive blood cultures is important for
      initiation of optimal treatment in septic patients. Effects of automated,
      microarray-based rapid identification systems on antibiotic prescription against
      community-onset bacteremia (COB) remain unclear. METHODS: We prospectively
      enrolled 177 patients with 185 COB episodes (occurring within 72 h of admission)
      over 17 months. Bacteremia episodes due to gram-positive bacteria (GP) and gram
      negative bacteria (GN) in the same patient were counted separately. For GP
      bacteremia, patients with >=2 sets of positive blood cultures were included. The
      primary study objective was evaluating the rates of antibiotic prescription
      changes within 2 days of rapid identification using the Verigene system. RESULTS:
      Bacteremia due to GN and GP included 144/185 (77.8%) and 41/185 (22.2%) episodes,
      respectively. Antibiotic prescription changes occurred in 51/185 cases (27.6%
      [95%CI:21.3-34.6%]) after Verigene analysis and 70/185 cases (37.8% [30.8-45.2%])
      after conventional identification and susceptibility testing. Prescription
      changes after Verigene identification were more frequent in GP (17/41[41.5%])
      than in GN (34/144[23.5%]). Among bacteremia due to single pathogen targeted by
      Verigene test, bacterial identification agreement between the two tests was high
      (GP: 38/39[97.4%], GN: 116/116[100%]). The Verigene test correctly predicted
      targeted antimicrobial resistance. The durations between the initiation of
      incubation and reporting of the results for the Verigene system and conventional
      test was 28.3 h (IQR: 25.8-43.4 h) and 90.6 h (68.3-118.4 h), respectively. In
      only four of the seven episodes of COB in which two isolates were identified by
      conventional tests, the Verigene test correctly identified both organisms.
      CONCLUSION: We observed a high rate of antibiotic prescription changes after the
      Verigene test in a population with COB especially in GP. The Verigene test would
      be a useful tool in antimicrobial stewardship programs among patients with COB.

PMID- 28742144
TI  - Genome-wide and protein kinase-focused RNAi screens reveal conserved and novel
      damage response pathways in Trypanosoma brucei.
AB  - All cells are subject to structural damage that must be addressed for continued
      growth. A wide range of damage affects the genome, meaning multiple pathways have
      evolved to repair or bypass the resulting DNA lesions. Though many repair
      pathways are conserved, their presence or function can reflect the life style of
      individual organisms. To identify genome maintenance pathways in a divergent
      eukaryote and important parasite, Trypanosoma brucei, we performed RNAi screens
      to identify genes important for survival following exposure to the alkylating
      agent methyl methanesulphonate. Amongst a cohort of broadly conserved and,
      therefore, early evolved repair pathways, we reveal multiple activities not so
      far examined functionally in T. brucei, including DNA polymerases, DNA helicases
      and chromatin factors. In addition, the screens reveal Trypanosoma- or
      kinetoplastid-specific repair-associated activities. We also provide focused
      analyses of repair-associated protein kinases and show that loss of at least
      nine, and potentially as many as 30 protein kinases, including a nuclear aurora
      kinase, sensitises T. brucei to alkylation damage. Our results demonstrate the
      potential for synthetic lethal genome-wide screening of gene function in T.
      brucei and provide an evolutionary perspective on the repair pathways that
      underpin effective responses to damage, with particular relevance for related
      kinetoplastid pathogens. By revealing that a large number of diverse T. brucei
      protein kinases act in the response to damage, we expand the range of eukaryotic
      signalling factors implicated in genome maintenance activities.

PMID- 28742145
TI  - Survival analysis of conservative vs. dialysis treatment of elderly patients with
      CKD stage 5.
AB  - Elderly patients represent a growing population among people suffering from ESRD.
      So far only limited data on actual survival benefits of elderly adults initiating
      dialysis have been published. Besides the high burden of preexisting
      comorbidities, dialysis treatment itself may be associated with a further
      deterioration in functional status in this population. We retrospectively
      analyzed the Austrian Dialysis and Transplant Registry and identified 8,622
      patients who started maintenance hemodialysis after the age of 65 years between
      2002 and 2009. We compared this data set to a cohort of 174 patients aged over 65
      years with CKD stage 5 who progressed to an eGFR < 10ml/min/ and were managed
      conservatively in the same era. All patients who died of malignant disease were
      excluded from this analysis. The risk of mortality was analyzed using
      multivariable Cox proportional hazards models. Furthermore, a parametric model of
      time to event analysis was used for visualization of changing risk over time and
      precise calculation of time to equal risk assuming a Weibull distribution.
      Hemodialysis treatment was associated with a decreased risk for death with a HR
      of 0.23 (95% CI 0.18 to 0.29; p<0.001) compared to conservative treatment. The
      time to event analysis however showed, that although survival was initially
      superior in the hemodialysis group, hazards crossed thereafter. Time to equal
      risk was 2.9 months and 1.9 months for female and male patient aged 65,
      respectively, and decreased to one month in the very elderly aged 95. Elderly
      patients with ERSD did benefit from initiation of hemodialysis, as the
      conservative group showed a very high initial mortality rate. This survival
      benefit of dialysis treatment however did not persist beyond the first two months
      compared to survivors of the conservative group.

PMID- 28742146
TI  - Immunomodulatory effects of excretory/secretory compounds from Contracaecum
      osculatum larvae in a zebrafish inflammation model.
AB  - Excretory/secretory (ES) compounds isolated from third-stage larvae of the
      anisakid nematode Contracaecum osculatum parasitizing liver of Baltic cod were
      investigated for effects on immune gene expression in a zebrafish LPS-induced
      inflammation model. ES products containing a series of proteins, of which some
      had enzymatic activity, were injected solely or with LPS. ES proteins alone
      induced up-regulation of a number of immune-related genes, but generally to a
      lower degree compared to LPS. When co-injected with LPS, the worm products
      exacerbated merely expression of five genes affecting Th1, Th2, Th17 and innate
      responses compared to the LPS-injected group. However, the level of
      overexpression decreased in an inverse dose-dependent manner. The immune
      regulating action of C. osculatum ES products is interpreted as an important
      evolutionary ability of larval parasites in the transport host which makes it
      less susceptible to host immune responses whereby the probability of reaching the
      final host is increased.

PMID- 28742147
TI  - Genetic analysis of the regulation of the voltage-gated calcium channel homolog
      Cch1 by the gamma subunit homolog Ecm7 and cortical ER protein Scs2 in yeast.
AB  - The yeast Cch1/Mid1 Ca2+ channel is equivalent to animal voltage-gated Ca2+
      channels and activated in cells incubated in low Ca2+ medium. We herein
      investigated the third subunit, Ecm7, under the same cell culture conditions. The
      deletion of ECM7 slightly lowered Ca2+ influx activity in the CNB1+ background,
      in which calcineurin potentially dephosphorylates Cch1, but markedly lowered this
      activity in the cnb1Delta background. The deletion of the C-terminal cytoplasmic
      region of Ecm7 also reduced Ca2+ influx activity. We identified a novel Cch1
      interacting protein, Scs2, which is known as a cortical endoplasmic reticulum
      membrane protein. The deletion of SCS2 did not affect Ca2+ influx activity when
      calcineurin was inhibited by FK506, but enhanced this activity by 35% when the
      enzyme was not inhibited. However, this enhancement was canceled by the deletion
      of ECM7. These results suggest that Cch1/Mid1 is regulated differentially by Ecm7
      and Scs2 in a manner that is dependent on the phosphorylation status of Cch1.

PMID- 28742148
TI  - Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates
      viral transcription.
AB  - The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic
      virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably
      adult T-cell leukemia. Tax governs the transcription from the viral 5'LTR,
      enhancing thereby its own expression, via the recruitment of dimers of
      phosphorylated CREB to cAMP-response elements located within the U3 region
      (vCRE). In addition to phosphorylation, CREB is also the target of O
      GlcNAcylation, another reversible post-translational modification involved in a
      wide range of diseases, including cancers. O-GlcNAcylation consists in the
      addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine
      residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which
      transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it. In this
      study, we investigated the status of O-GlcNAcylation enzymes in HTLV-1
      transformed T cells. We found that OGA mRNA and protein expression levels are
      increased in HTLV-1-transformed T cells as compared to control T cell lines while
      OGT expression is unchanged. However, higher OGA production coincides with a
      reduction in OGA specific activity, showing that HTLV-1-transformed T cells
      produce high level of a less active form of OGA. Introducing Tax into HEK-293T
      cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit
      OGA activity and increase total O-GlcNAcylation, without any change in OGT
      activity. Furthermore, Tax interacts with the OGT/OGA complex and inhibits the
      activity of OGT-bound OGA. Pharmacological inhibition of OGA increases CREB O
      GlcNAcylation as well as HTLV-1-LTR transactivation by Tax and CREB recruitment
      to the LTR. Moreover, overexpression of wild-type CREB but not a CREB protein
      mutated on a previously described O-GlcNAcylation site enhances Tax-mediated LTR
      transactivation. Finally, both OGT and OGA are recruited to the LTR. These
      findings reveal the interplay between Tax and the O-GlcNAcylation pathway and
      identify new key molecular actors involved in the assembly of the Tax-dependent
      transactivation complex.

PMID- 28742149
TI  - Predicting the risk of Lyme borreliosis after a tick bite, using a structural
      equation model.
AB  - BACKGROUND: Understanding and quantification of the risk of Lyme borreliosis
      after a tick bite can aid development of prevention strategies against Lyme
      borreliosis. METHODS: We used 3,525 single tick bite reports from three large
      prospective studies on the transmission risk of tick-borne pathogens to humans,
      with 50 reports of Lyme borreliosis during the follow-up period, among 1,973
      reports with known outcome. A structural equation model was applied to estimate
      the risk of Lyme borreliosis after a tick bite, and quantify the influence of:
      developmental stage of the tick, detection of Borrelia burgdorferi s.l. DNA in
      the tick by PCR, tick engorgement, patient-estimated duration of tick attachment,
      and patient age. RESULTS: The overall risk of developing Lyme borreliosis after a
      tick bite was 2.6% (95%CI 1.4-5.1). The risk increased with: - Tick engorgement:
      1.4% (95%CI 0.7%-2.3%) for low engorgement to 5.5% (95%CI 2.8%-9.2%) for
      substantially engorged ticks;- Rising patient-estimated tick attachment duration:
      2.0% (95%CI 1.3%-2.8%) after <12 hours, to 5.2% (95%CI 3.0%-8.9%) after >=4 days;
      Detection of Borrelia burgdorferi s.l. DNA in ticks: 6.7% (95%CI 3.6%-13.5%),
      versus 1.4% (95%CI 0.7%-2.9%) when ticks tested negative.The highest observed
      risk of Lyme borreliosis was 14.4% (95%CI 6.8%-24.6%) after one tick bite of a
      substantially engorged tick that tested positive for Borrelia burgdorferi s.l.
      DNA, which corresponds to one new case of Lyme borreliosis per 7 (95%CI 4-15) of
      such tick bites. CONCLUSIONS: An individual's risk of Lyme borreliosis after a
      tick bite can be predicted with tick engorgement, patient-estimated duration of
      tick attachment, and detection of Borrelia burgdorferi s.l. DNA in the tick.

PMID- 28742150
TI  - Cancer incidence rates and trends among children and adolescents in Piedmont,
      1967-2011.
AB  - In the past, increases in childhood cancer incidence were reported in Europe and
      North America. The aim of this study is to show updated patterns of temporal
      behavior using data of the Childhood Cancer Registry of Piedmont (CCRP), a region
      with approximately 4.5 million inhabitants in North-West Italy. CCRP has been
      recording incident cases in children (0-14 years) since 1967 and in adolescents
      (15-19) since 2000. Time trends were estimated as annual percent change (APC)
      over the 1976-2011 period for children, and over 2000-2011 for both children and
      adolescents. CCRP registered 5020 incident cases from 1967 to 2011. Incidence
      rates were 157 per million person-years for children (1967-2011) and 282 for
      adolescents (2000-2011). From 1976-2011, increasing trends were observed in
      children for all neoplasms (APC 1.1, 95%CI: 0.8; 1.5) and for both embryonal and
      non-embryonal tumors: 1.1%, (0.5; 1.6) and 1.2%, (0.7; 1.6), respectively.
      Increases were observed in several tumor types, including leukemia, lymphoma,
      central nervous system tumors and neuroblastoma. In 2000-2011, incidence rates
      showed mostly non statistically significant variations and large variability. The
      observation of trends over a long period shows that the incidence of most tumors
      has increased, and this is only partially explained by diagnostic changes. Large
      rate variability hampers interpretation of trend patterns in short periods. Given
      that no satisfying explanation for the increases observed in the past was ever
      found, efforts must be made to understand and interpret this peculiar and still
      ununderstood pattern of childhood cancer incidence.

PMID- 28742151
TI  - Exploring the cross talk between ER stress and inflammation in age-related
      macular degeneration.
AB  - Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER)
      stress is implicated in the development and progression of age-related macular
      degeneration (AMD), a multifactorial neurodegenerative disease. However the cross
      talk between these cellular mechanisms has not been clearly and fully understood.
      The present study investigates a possible intersection between ER stress and
      inflammation in AMD. In this study, we recruited two collections of involved
      protein markers to retrieve their interaction information from IMEx-curated
      databases, which are the most well- known protein-protein interaction
      collections, allowing us to design an intersection network for AMD that is
      unprecedented. In order to find expression activated subnetworks, we utilized AMD
      expression profiles in our network. In addition, we studied topological
      characteristics of the most expressed active subnetworks to identify the hubs.
      With regard to topological quantifications and expressional activity, we reported
      a list of the most pivotal hubs which are potentially applicable as probable
      therapeutic targets. Furthermore, we introduced MAPK signaling pathway as a
      significantly involved pathway in the association between ER stress and
      inflammation, leading to promising new directions in discovering AMD formation
      mechanisms and possible treatments.

PMID- 28742152
TI  - Bacterial size matters: Multiple mechanisms controlling septum cleavage and
      diplococcus formation are critical for the virulence of the opportunistic
      pathogen Enterococcus faecalis.
AB  - Enterococcus faecalis is an opportunistic pathogen frequently isolated in
      clinical settings. This organism is intrinsically resistant to several clinically
      relevant antibiotics and can transfer resistance to other pathogens. Although E.
      faecalis has emerged as a major nosocomial pathogen, the mechanisms underlying
      the virulence of this organism remain elusive. We studied the regulation of
      daughter cell separation during growth and explored the impact of this process on
      pathogenesis. We demonstrate that the activity of the AtlA peptidoglycan
      hydrolase, an enzyme dedicated to septum cleavage, is controlled by several
      mechanisms, including glycosylation and recognition of the peptidoglycan
      substrate. We show that the long cell chains of E. faecalis mutants are more
      susceptible to phagocytosis and are no longer able to cause lethality in the
      zebrafish model of infection. Altogether, this work indicates that control of
      cell separation during division underpins the pathogenesis of E. faecalis
      infections and represents a novel enterococcal virulence factor. We propose that
      inhibition of septum cleavage during division represents an attractive
      therapeutic strategy to control infections.

PMID- 28742153
TI  - Reconstructing the regulatory circuit of cell fate determination in yeast mating
      response.
AB  - Massive technological advances enabled high-throughput measurements of proteomic
      changes in biological processes. However, retrieving biological insights from
      large-scale protein dynamics data remains a challenging task. Here we used the
      mating differentiation in yeast Saccharomyces cerevisiae as a model and developed
      integrated experimental and computational approaches to analyze the proteomic
      dynamics during the process of cell fate determination. When exposed to a high
      dose of mating pheromone, the yeast cell undergoes growth arrest and forms a
      shmoo-like morphology; however, at intermediate doses, chemotropic elongated
      growth is initialized. To understand the gene regulatory networks that control
      this differentiation switch, we employed a high-throughput microfluidic imaging
      system that allows real-time and simultaneous measurements of cell growth and
      protein expression. Using kinetic modeling of protein dynamics, we classified the
      stimulus-dependent changes in protein abundance into two sources: global changes
      due to physiological alterations and gene-specific changes. A quantitative
      framework was proposed to decouple gene-specific regulatory modes from the growth
      dependent global modulation of protein abundance. Based on the temporal patterns
      of gene-specific regulation, we established the network architectures underlying
      distinct cell fates using a reverse engineering method and uncovered the dose
      dependent rewiring of gene regulatory network during mating differentiation.
      Furthermore, our results suggested a potential crosstalk between the pheromone
      response pathway and the target of rapamycin (TOR)-regulated ribosomal biogenesis
      pathway, which might underlie a cell differentiation switch in yeast mating
      response. In summary, our modeling approach addresses the distinct impacts of the
      global and gene-specific regulation on the control of protein dynamics and
      provides new insights into the mechanisms of cell fate determination. We
      anticipate that our integrated experimental and modeling strategies could be
      widely applicable to other biological systems.

PMID- 28742154
TI  - Lipopolysaccharide inhibits myogenic differentiation of C2C12 myoblasts through
      the Toll-like receptor 4-nuclear factor-kappaB signaling pathway and myoblast
      derived tumor necrosis factor-alpha.
AB  - BACKGROUND: Circulating lipopolysaccharide (LPS) concentrations are often
      elevated in patients with sepsis or with various endogenous diseases that are
      associated with metabolic endotoxemia. Involuntary loss of skeletal muscle,
      termed muscle wasting, is commonly observed in these conditions, suggesting that
      circulating LPS might play an essential role in its development. Although
      impairment of muscle regeneration is an important determinant of skeletal muscle
      wasting, it is unclear whether LPS affects this process and, if so, by what
      mechanism. Here, we used the C2C12 myoblast cell line to investigate the effects
      of LPS on myogenesis. METHODS: C2C12 myoblasts were grown to 80% confluence and
      induced to differentiate in the absence or presence of LPS (0.1 or 1 MUg/mL); TAK
      242 (1 MUM), a specific inhibitor of Toll-like receptor 4 (TLR4) signaling; and a
      tumor necrosis factor (TNF)-alpha neutralizing antibody (5 MUg/mL). Expression of
      a skeletal muscle differentiation marker (myosin heavy chain II), two essential
      myogenic regulatory factors (myogenin and MyoD), and a muscle negative regulatory
      factor (myostatin) was analyzed by western blotting. Nuclear factor-kappaB (NF
      kappaB) DNA-binding activity was measured using an enzyme-linked immunosorbent
      assay. RESULTS: LPS dose-dependently and significantly decreased the formation of
      multinucleated myotubes and the expression of myosin heavy chain II, myogenin,
      and MyoD, and increased NF-kappaB DNA-binding activity and myostatin expression.
      The inhibitory effect of LPS on myogenic differentiation was reversible,
      suggesting that it was not caused by nonspecific toxicity. Both TAK-242 and anti
      TNF-alpha reduced the LPS-induced increase in NF-kappaB DNA-binding activity,
      downregulation of myogenic regulatory factors, and upregulation of myostatin,
      thereby partially rescuing the impairment of myogenesis. CONCLUSIONS: Our data
      suggest that LPS inhibits myogenic differentiation via a TLR4-NF-kappaB-dependent
      pathway and an autocrine/paracrine TNF-alpha-induced pathway. These pathways may
      be involved in the development of muscle wasting caused by sepsis or metabolic
      endotoxemia.

PMID- 28742155
TI  - Acceleration of the sliding movement of actin filaments with the use of a non
      motile mutant myosin in in vitro motility assays driven by skeletal muscle heavy
      meromyosin.
AB  - We examined the movement of an actin filament sliding on a mixture of normal and
      genetically modified myosin molecules that were attached to a glass surface. For
      this purpose, we used a Dictyostelium G680V mutant myosin II whose release rates
      of Pi and ADP were highly suppressed relative to normal myosin, leading to a
      significantly extended life-time of the strongly bound state with actin and
      virtually no motility. When the mixing ratio of G680V mutant myosin II to
      skeletal muscle HMM (heavy myosin) was 0.01%, the actin filaments moved
      intermittently. When they moved, their sliding velocities were about two-fold
      faster than the velocity of skeletal HMM alone. Furthermore, sliding movements
      were also faster when the actin filaments were allowed to slide on skeletal
      muscle HMM-coated glass surfaces in the motility buffer solution containing G680V
      HMM. In this case no intermittent movement was observed. When the actin filaments
      used were copolymerized with a fusion protein consisting of Dictyostelium actin
      and Dictyostelium G680V myosin II motor domain, similar faster sliding movements
      were observed on skeletal muscle HMM-coated surfaces. The filament sliding
      velocities were about two-fold greater than the velocities of normal actin
      filaments. We found that the velocity of actin filaments sliding on skeletal
      muscle myosin molecules increased in the presence of a non-motile G680V mutant
      myosin motor.

PMID- 28742156
TI  - CT pattern analysis of necrotizing and nonnecrotizing lymph nodes in Kikuchi
      disease.
AB  - OBJECTIVE: The purpose of this study was to determine whether a CT interpretation
      with imaging pattern analysis differentiates Kikuchi disease (KD) from the two
      more frequently encountered differential lymph nodes diagnoses of tuberculous
      lymphadenopathy (TL) and reactive hyperplasia (RH). MATERIALS AND METHODS:
      Between January 2012 and July 2015, 20 patients with KD (6 men, 14 women; mean
      age, 27.80 years), 36 patients with RH (10 men, 26 women; mean age, 33.08 years)
      and 34 patients with TL (17 men, 17 women; mean age, 39.82 years) were
      pathologically diagnosed using US-guided fine needle aspiration biopsy, core
      needle biopsy, or surgical excisional biopsy. We recorded the total number,
      location, and size of the affected cervical lymph nodes, and two radiologists
      reviewed the characteristic imaging findings, including the presence of necrosis,
      cortical enhancement pattern, perinodal infiltration, conglomeration and nodal
      calcification, to form a consensus. In addition, we compared two attenuation
      indices on the nonnecrotic portion of the affected lymph nodes, nodal cortical
      attenuation (NCA) and the ratio of NCA to the adjacent muscle (NCA/M). RESULTS:
      Conglomeration, enhancement pattern and NCA/M values were independent predictive
      CT features to distinguish KD from RH. Age and enhancement pattern discriminated
      KD from TL. Only the mean NCA/M value was a statistically significant CT feature
      (p = .008) in differentiating KD from both RH+TL. The mean NCA/M of KD (1.67 +/-
      0.20) was significantly higher than that of RH (1.49 +/- 0.20) or TL (1.47 +/-
      0.21). CONCLUSION: Our results indicate that in case of nonnecrotic
      lymphadenopathy, a higher NCA/M index can differentiate KD from RH and TL. In
      addition, the enhancement pattern according to the degree of necrosis
      discriminated between KD and TL in the case of necrotic lymphadenopathy.

PMID- 28742157
TI  - Angiotensin II system in the nucleus tractus solitarii contributes to autonomic
      dysreflexia in rats with spinal cord injury.
AB  - BACKGROUND: Autonomic dysreflexia (AD) is a potentially life-threating
      complication after spinal cord injury (SCI), characterized by episodic
      hypertension induced by colon or bladder distension. The objective of this study
      was to determine the role of impaired baroreflex regulation by the nucleus
      tractus solitarii(NTS) in the occurrence of AD in a rat model. METHODS: T4 spinal
      cord transection animal model was used in this study, which included 40 Male rats
      Colorectal distension (CD) was performed to assess AD and compare the changes of
      BP, HR, and BRS, six weeks after operation. After that, SCI rats with
      successfully induced AD were selected. Losartan was microinjected into NTS in SCI
      rats, then 10, 30, 60 minutes later, CD was performed to calculate the changes of
      BP, HR, and BRS in order to explicit whether Ang II system was involved in the AD
      occurrence. Ang II was then Intra-cerebroventricular infused in sham operation
      rats with CD to mimic the activation of Ang II system in AD. Finally, the level
      of Ang II in NTS and colocalization of AT1R and NMDA receptor within the NTS
      neurons were also detected in SCI rats. RESULTS: Compared with sham operation,
      SCI significantly aggravated the elevation of blood pressure (BP) and impaired
      baroreflex sensitivity (BRS) induced by colorectal distension; both of which were
      significantly improved by microinjection of the angiotensin receptor type I
      (AT1R) antagonist losartan into the NTS. Level of angiotensin II (Ang II) in the
      NTS was significantly increased in the SCI rats than sham.
      Intracerebroventricular infusion of Ang II also mimicked changes in BP and BRS
      induced by colorectal distension. Blockade of baroreflex by sinoaortic
      denervation prevented beneficial effect of losartan on AD. CONCLUSION: We
      concluded that the activation of Ang II system in NTS may impair blood pressure
      baroreflex, and contribute to AD after SCI.

PMID- 28742158
TI  - Human Tamm-Horsfall protein, a renal specific protein, serves as a cofactor in
      complement 3b degradation.
AB  - Tamm-Horsfall protein (THP) is an abundant urinary protein of renal origin. We
      hypothesize that THP can act as an inhibitor of complement since THP binds
      complement 1q (C1q) of the classical complement pathway, inhibits activation of
      this pathway, and is important in decreasing renal ischemia-reperfusion injury (a
      complement-mediated condition). In this study, we began to investigate whether
      THP interacted with the alternate complement pathway via complement factor H
      (CFH). THP was shown to bind CFH using ligand blots and in an ELISA (KD of 1 * 10
      6 M). Next, the ability of THP to alter CFH's normal action as it functioned as a
      cofactor in complement factor I (CFI)-mediated complement 3b (C3b) degradation
      was investigated. Unexpectedly, control experiments in these in vitro assays
      suggested that THP, without added CFH, could act as a cofactor in CFI-mediated
      C3b degradation. This cofactor activity was present equally in THP isolated from
      10 different individuals. While an ELISA demonstrated small amounts of CFH
      contaminating THP samples, these CFH amounts were insufficient to explain the
      degree of cofactor activity present in THP. An ELISA demonstrated that THP
      directly bound C3b (KD ~ 5 * 10-8 m), a prerequisite for a protein acting as a
      C3b degradation cofactor. The cofactor activity of THP likely resides in the
      protein portion of THP since partially deglycosylated THP still retained cofactor
      activity. In conclusion, THP appears to participate directly in complement
      inactivation by its ability to act as a cofactor for C3b degradation, thus adding
      support to the hypothesis that THP might act as an endogenous urinary tract
      inhibitor of complement.

PMID- 28742159
TI  - beta-adrenergic signaling broadly contributes to LTP induction.
AB  - Long-lasting forms of long-term potentiation (LTP) represent one of the major
      cellular mechanisms underlying learning and memory. One of the fundamental
      questions in the field of LTP is why different molecules are critical for long
      lasting forms of LTP induced by diverse experimental protocols. Further
      complexity stems from spatial aspects of signaling networks, such that some
      molecules function in the dendrite and some are critical in the spine. We
      investigated whether the diverse experimental evidence can be unified by creating
      a spatial, mechanistic model of multiple signaling pathways in hippocampal CA1
      neurons. Our results show that the combination of activity of several key kinases
      can predict the occurrence of long-lasting forms of LTP for multiple experimental
      protocols. Specifically Ca2+/calmodulin activated kinase II, protein kinase A and
      exchange protein activated by cAMP (Epac) together predict the occurrence of LTP
      in response to strong stimulation (multiple trains of 100 Hz) or weak stimulation
      augmented by isoproterenol. Furthermore, our analysis suggests that activation of
      the beta-adrenergic receptor either via canonical (Gs-coupled) or non-canonical
      (Gi-coupled) pathways underpins most forms of long-lasting LTP. Simulations make
      the experimentally testable prediction that a complete antagonist of the beta
      adrenergic receptor will likely block long-lasting LTP in response to strong
      stimulation. Collectively these results suggest that converging molecular
      mechanisms allow CA1 neurons to flexibly utilize signaling mechanisms best tuned
      to temporal pattern of synaptic input to achieve long-lasting LTP and memory
      storage.

PMID- 28742160
TI  - Sub-classification of myopic glaucomatous eyes according to optic disc and
      peripapillary features.
AB  - PURPOSE: To investigate the sub-classification of myopic glaucomatous eyes by
      optic disc and peripapillary features. METHODS: Optic disc tilt and torsion were
      determined from retinal nerve fiber layer photographs. Based on the location of
      the Bruch's membrane (BM) opening within the beta-zone of the peripapillary
      atrophy (PPA) area, the widths of beta-zone PPA (PPA1W), PPA+BM (PPA2W), and PPA
      BM (PPA3W) were measured with enhanced depth imaging spectral-domain optical
      coherence tomography. Cluster analysis that employed partitioning around medoids
      was performed with these parameters, the presence of inward rotation of BM ending
      axial length (AXL), and central corneal thickness. RESULTS: A total of 115 eyes
      (AXL>=24 mm) were included. Two clusters produced maximum overall silhouette
      widths (average = 0.43). Visual field (VF) mean deviation was not different
      between cluster 1 (52 eyes; -4.02+/-3.01 dB) and cluster 2 (63 eyes; -5.21+/-5.62
      dB; p = 0.174). In cluster 1 compared to cluster 2, optic disc tilt was
      significantly greater, PPA1W and PPA3W were longer, and AXL was longer (all
      p<0.001). The presence of an inward rotation of BM ending was more frequent in
      cluster 2 (p = 0.043). Forty-one eyes (78.8%) in cluster 1 had superior VF
      defects while 10 eyes (19.2%) had inferior defects, and only one eye (2%) had
      defects in both hemifields. Eyes in cluster 2 were more evenly distributed: 55.6%
      had superior defects, 34.9% had inferior defects, and 9.5% had defects in both
      hemifields (p = 0.023). CONCLUSIONS: Myopic glaucomatous eyes characterized by
      optic disc and peripapillary configurations can be classified as two distinct
      types, and the most distinct difference between the two was degree of optic disc
      tilt and width of PPA. The location of VF defects were also significantly
      different between two clusters.

PMID- 28742161
TI  - Abundance and co-occurrence of extracellular capsules increase environmental
      breadth: Implications for the emergence of pathogens.
AB  - Extracellular capsules constitute the outermost layer of many bacteria, are major
      virulence factors, and affect antimicrobial therapies. They have been used as
      epidemiological markers and recently became vaccination targets. Despite the
      efforts to biochemically serotype capsules in a few model pathogens, little is
      known of their taxonomic and environmental distribution. We developed, validated,
      and made available a computational tool, CapsuleFinder, to identify capsules in
      genomes. The analysis of over 2500 prokaryotic genomes, accessible in a database,
      revealed that ca. 50% of them-including Archaea-encode a capsule. The Wzx/Wzy
      dependent capsular group was by far the most abundant. Surprisingly, a fifth of
      the genomes encode more than one capsule system-often from different groups-and
      their non-random co-occurrence suggests the existence of negative and positive
      epistatic interactions. To understand the role of multiple capsules, we queried
      more than 6700 metagenomes for the presence of species encoding capsules and
      showed that their distribution varied between environmental categories and,
      within the human microbiome, between body locations. Species encoding capsules,
      and especially those encoding multiple capsules, had larger environmental
      breadths than the other species. Accordingly, capsules were more frequent in
      environmental bacteria than in pathogens and, within the latter, they were more
      frequent among facultative pathogens. Nevertheless, capsules were frequent in
      clinical samples, and were usually associated with fast-growing bacteria with
      high infectious doses. Our results suggest that capsules increase the
      environmental range of bacteria and make them more resilient to environmental
      perturbations. Capsules might allow opportunistic pathogens to profit from empty
      ecological niches or environmental perturbations, such as those resulting from
      antibiotic therapy, to colonize the host. Capsule-associated virulence might thus
      be a by-product of environmental adaptation. Understanding the role of capsules
      in natural environments might enlighten their function in pathogenesis.

PMID- 28742162
TI  - Trajectories of anxiety and health related quality of life during pregnancy.
AB  - Anxiety and health related Quality of Life (HRQoL) have emerged as important
      mental health measures in obstetric care. Few studies have systematically
      examined the longitudinal trajectories of anxiety and HRQoL in pregnancy. Using a
      linear growth modeling strategy, we analyzed the course of State-Trait Anxiety
      Inventory (STAI)- and Short Form (36) Health Survey (SF-36) scores between the
      12th and the 36th week of gestation, in a sample of 355 women. We additionally
      analyzed the impact of depressive symptoms and a chronic medical condition
      (asthma), on STAI and SF-36 trajectory curves. STAI scores remained stable
      throughout pregnancy. A previous history of anxiety increased the overall STAI
      scores. Asthma and depressive symptoms scores had no impact on the STAI
      trajectory. Physical SF-36 scores decreased over the course of pregnancy, whereas
      mental SF-36 trended towards improvement. Asthma reduced physical SF-36 overall.
      While high depressive symptoms decreased the overall mental SF-36, they were also
      significantly associated with mental SF-36 improvements over time. Anxiety
      symptoms are stable during pregnancy and are not modulated by depressive symptoms
      or asthma. Physical HRQoL declines in pregnancy. In contrast, mental HRQoL
      appears to improve, particularly in women with high initial levels of depressive
      symptoms.

PMID- 28742163
TI  - Debunking in a world of tribes.
AB  - Social media aggregate people around common interests eliciting collective
      framing of narratives and worldviews. However, in such a disintermediated
      environment misinformation is pervasive and attempts to debunk are often
      undertaken to contrast this trend. In this work, we examine the effectiveness of
      debunking on Facebook through a quantitative analysis of 54 million users over a
      time span of five years (Jan 2010, Dec 2014). In particular, we compare how users
      usually consuming proven (scientific) and unsubstantiated (conspiracy-like)
      information on Facebook US interact with specific debunking posts. Our findings
      confirm the existence of echo chambers where users interact primarily with either
      conspiracy-like or scientific pages. However, both groups interact similarly with
      the information within their echo chamber. Then, we measure how users from both
      echo chambers interacted with 50,220 debunking posts accounting for both users
      consumption patterns and the sentiment expressed in their comments. Sentiment
      analysis reveals a dominant negativity in the comments to debunking posts.
      Furthermore, such posts remain mainly confined to the scientific echo chamber.
      Only few conspiracy users engage with corrections and their liking and commenting
      rates on conspiracy posts increases after the interaction.

PMID- 28742164
TI  - Relationship between implant stability on the abutment and platform level by
      means of resonance frequency analysis: A cross-sectional study.
AB  - Resonance frequency analysis (RFA) has become the main tool used to assess the
      osseointegration of dental implants. The objective of this study was to verify
      the relationship between the ISQ values with different prosthetic abutments and
      with the implant platform. The hypothesis was that ISQ values changes according
      to the abutment height. Twelve patients were included, whose contribution to the
      study was 31 dental implants (external hexagon connection implants, 4.1x10 mm).
      The temporary implant-supported crown and prosthetic components were removed and
      the following smartpegs were inserted, one at a time: type 1, in the implant
      platform (G1); type A3, in the microunit component with 1mm transmucosal height
      (G2) and type A3, in the microunit component with 5mm transmucosal height (G3).
      In all the smartpegs, RFA measurements were taken on mesial, distal, buccal and
      lingual surfaces. All evaluations were performed by a single calibrated examiner
      (ICC = 0.989). Data were analyzed by Friedman and Spearman correlation tests and
      log-linear marginal regression (p<0.05). The mean age of participants was 52.83
      (+/- 3.77) years. There was statistically significant difference (p<0.001) among
      the mean ISQ of G1 (88.27 +/-5.70); G2 (72.75 +/-4.73) and G3 (66.33 +/-3.67).
      There was statistically significant negative correlation between the ISQ and the
      measurement distance (rs:-0.852; p<0.001; R2:0.553). Measurement distance was
      significantly associated (p<0.001) with ISQ value in the log-linear regression.
      The abutment height has a significant impact on resonance frequency analysis
      measurements. The higher the transmucosal abutment height, the lower the implant
      stability quotient value. Clinically, the ISQ measured on the abutment cannot be
      compared with values measured on the implant platform.

PMID- 28742165
TI  - System analysis identifies distinct and common functional networks governed by
      transcription factor ASCL1, in glioma and small cell lung cancer.
AB  - ASCL1 is a basic Helix-Loop-Helix transcription factor (TF), which is involved in
      various cellular processes like neuronal development and signaling pathways.
      Transcriptome profiling has shown that ASCL1 overexpression plays an important
      role in the development of glioma and Small Cell Lung Carcinoma (SCLC), but
      distinct and common molecular mechanisms regulated by ASCL1 in these cancers are
      unknown. In order to understand how it drives the cellular functional network in
      these two tumors, we generated a gene expression profile in a glioma cell line
      (U87MG) to identify ASCL1 gene targets by an si RNA silencing approach and then
      compared this with a publicly available dataset of similarly silenced SCLC (NCI
      H1618 cells). We constructed TF-TF and gene-gene interactions, as well as protein
      interaction networks of ASCL1 regulated genes in glioma and SCLC cells. Detailed
      network analysis uncovered various biological processes governed by ASCL1 target
      genes in these two tumor cell lines. We find that novel ASCL1 functions related
      to mitosis and signaling pathways influencing development and tumor growth are
      affected in both glioma and SCLC cells. In addition, we also observed ASCL1
      governed functional networks that are distinct to glioma and SCLC.

PMID- 28742178
TI  - ?

PMID- 28742179
TI  - [The benefit of health care].

PMID- 28742180
TI  - ?

PMID- 28742181
TI  - ?

PMID- 28742182
TI  - [Injecting drug users obvious target for hepatitis C treatment].

PMID- 28742183
TI  - ?

PMID- 28742184
TI  - ?

PMID- 28742185
TI  - ?

PMID- 28742186
TI  - ?
AB  - Loose peritoneal cysts - unexpected finding at laparoscopic surgery for suspected
      extrauterine pregnancy, a case report A 29 year old woman was admitted to
      inpatient care in the 7th week of pregnancy due to three previous episodes of
      abdominal pain. At admission a suspected pseudogestational sac and 2 * 3
      centimetres of fluid in the cul-de-sac was noted at vaginal ultrasound
      examination. After two days she again developed pain and a laparoscopy was
      performed due to suspected extrauterine pregnancy. Instead, three clusters of
      thin-walled, clear cysts was found lying loose in the cul-de-sac. There were also
      signs of endometriosis. The abdominal pain resolved gradually. At follow-up after
      one week a missed abortion was diagnosed. The pathologic-anatomic diagnosis was
      benign peritoneal cysts. Loose cysts are a more rare form of peritoneal inclusion
      cysts. They are benign but the risk of reoccurrence is about 50%. Some previous
      case reports indicate that growth of peritoneal cysts can be stimulated by
      pregnancy. In this case it is however unlikely that the small, loose cysts caused
      the woman's pain.

PMID- 28742187
TI  - ?
AB  - Pulmonary hypertension due to lung diseases In 2015 the European Society of
      Cardiology and European Respiratory Society published new guidelines on the
      diagnosis and treatment of pulmonary hypertension (PH). PH due to lung diseases
      and/or hypoxia was classified as a separate entity. PH is common in lung
      diseases, but seldom severe. Nevertheless, the presence of PH in a patient with
      lung disease is associated with worse outcome. If there is clinical suspicion of
      PH in a patient with lung disease, echocardiography is recommended, and if there
      are signs of severe PH and/or severe right ventricular dysfunction the patient
      should be referred to a PH expert centre. Patients may have lung disease and e.g.
      pulmonary arterial hypertension or chronic thromboembolic PH simultaneously, and
      targeted treatments are available in such cases. PH-targeted drugs should,
      however, not be used to treat PH due to lung diseases, since there are no robust
      data speaking for their benefit and a risk of impaired arterial oxygenation due
      to inhibition of hypoxic pulmonary vasoconstriction. Instead, the underlying lung
      disease should be optimally treated, including long-term oxygen therapy in case
      of chronic hypoxemia.

PMID- 28742188
TI  - ?
AB  - Infant botulism - why honey should be avoided for children up to one year Infant
      botulism means that Clostridium botulinum colonize and produce toxin in the
      infant gut, usually during the first year of life. Illness severity varies widely
      and the incidence may be under-estimated. Infant botulism should be considered in
      cases of acute muscle weakness or floppiness in infants, especially when
      accompanied by constipation or feeding difficulties. Respiratory failure and need
      for mechanical ventilation is common, but full recovery is gradually obtained.
      Diagnosis is based on stool culture and toxin detection in stool. Botulinum
      spores are frequently present in honey, which should consequently be avoided for
      infants.

PMID- 28742189
TI  - Novel endogenous negative modulators of platelet function as potential anti
      thrombotic targets.
AB  - Platelets are megakaryocyte-derived nuclear-free fragments that participate in
      cardiovascular diseases including acute myocardial infarction, ischemic stroke,
      hypertension, and atherosclerosis. At the endothelium damage site, platelets
      interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor
      gamma-chain (GPVI/FcRgamma), G protein-coupled receptor/phospholipase
      Cgamma(beta) (GPCR/PLCgamma(beta)), Rho/RhoK and integrin. The activation of
      these signaling pathways triggers intracellular calcium increase and causes
      platelet adhesion, aggregation, granule release and finally thrombus formation.
      Some endogenous platelet modulators reported to negatively regulate this process
      are: (1) platelet surface inhibitory receptors: carcinoembryonic antigen cell
      adhesion molecule 1, 2 (CEACAM 1, 2), platelet endothelial cell adhesion molecule
      1 (PECAM-1), and G6b-B; (2) nuclear receptors: retinoic X receptor (RXRs),
      glucocorticoid receptor (GR), peroxisome proliferator-activated receptors (PPARs)
      and liver X receptors (LXRs); (3) intracellular adaptor proteins: CLP36,
      paxillin, downstream of tyrosine kinase (Dok), c-Casitas B-lineage lymphoma (c
      Cbl), protein kinase Cdelta (PKCdelta), glycogen synthase kinase(GSK)-3beta,
      phospholipase D2 (PLD2), peroxiredoxin II (PrxII), T-cell ubiquitin ligand-2
      (TULA-2); (4) extracellular modulators released from platelet granules: adapter
      protein disabled-2 (DAB2) and diadenosine 5,5-P1, P2-diphosphate (Ap2A). The
      discovery of biological or endogenous modulators of platelet activation is
      regarded as a potential therapeutic target for thrombotic disease. This review
      highlights the recent findings on the endogenous negative regulatory molecules
      released from platelets and their impact on platelet thrombus formation.

PMID- 28742190
TI  - The research on the influences of hyperthermal perfusion chemotherapy combined
      with immunologic therapy on the immunologic function and levels of circulating
      tumor cells of the advanced colorectal cancer patients with liver metastasis.
AB  - OBJECTIVE: To investigated the influence of hyperthermal perfusion chemotherapy
      combined with immunologic therapy on the immunologic function and levels of
      circulating tumor cells of the advanced colorectal cancer patients with liver
      metastasis. PATIENTS AND METHODS: We enrolled 98 advanced colorectal cancer
      patients with liver metastasis that were admitted to this hospital for treatment
      and were randomly divided into two groups, the observation group (n = 49) and the
      control group (n = 49). We administered systemic vein chemotherapy for patients
      in the control group, and hyperthermal perfusion chemotherapy for the patients in
      the observation group in order to compare the subgroup levels of T lymphocytes,
      NK cells and immunoglobulin (IgG, IgA, and IgM) in the immune system of patients
      in both groups. We also assayed the circulating tumor cells (CTC) in the
      peripheral blood of patients in both groups using the cell search method, and
      compared the efficacy using response evaluation criteria in solid tumors and the
      survival rates of patients in both groups using the Kaplan-Meier method. RESULTS:
      After two treatment courses, the levels of CD3+, CD4+ and CD4+/CD8+ of the
      patients in the observation group were significantly higher than those of the
      control group, but the levels of CD8+ of patients in the observation group was
      lower than that in the control group (p< 0.05). The levels of immunoglobulins
      (IgG, IgA, and IgM) in the observation group were higher than the control group
      (p < 0.05). The levels of NK cell cells were significantly lower than the control
      group (p < 0.05). The objective response rate, as well as the disease control
      rate of the observation group, were remarkably higher than those of the control
      group (p < 0.05). Compared to the control group, the observation group enjoyed a
      prolonged survival time, higher survival rate and significantly lower positive
      rate of CTC (p < 0.05). CONCLUSIONS: Better efficacy and tolerance, fewer toxic
      and side effects, improvement in the immunologic functions of patients for the
      indirect anti-tumor effect, a significant decrease in CTC of patients, and a
      higher long-term survival rate have been achieved in the treatment with
      hyperthermal perfusion chemotherapy combined with immunologic therapy for the
      advanced colorectal cancer patients with liver metastasis. Thus, it can serve as
      the preferable drug for the treatment of advanced colorectal cancer with liver
      metastasis.

PMID- 28742191
TI  - High progesterone levels during the luteal phase related to the use of an
      aromatase inhibitor in breast cancer patients.
AB  - OBJECTIVE: To evaluate the hormonal profile in three breast cancer patients who
      underwent controlled ovarian stimulation in the presence of the aromatase
      inhibitor letrozole. PATIENTS AND METHODS: In IVF University referral center, a
      case series of three breast cancer patients who underwent controlled ovarian
      stimulation (COS) with recombinant FSH and letrozole were investigated. Ovulation
      was induced with hCG (case No. 1) or with GnRH agonist (case No. 2-3). The
      primary outcome of our study was the detection of progesterone levels in the
      luteal phase. RESULTS: Very high progesterone values (mean 186.6 +/- 43.6 ng/mL)
      during the luteal phase were recorded in all three cases. CONCLUSIONS: High
      progesterone levels can be related to the use of letrozole independently of the
      most commonly used trigger regimen. Although progesterone has long been
      considered a protective factor against breast cancer, several studies have
      demonstrated that progesterone could expand a transformation-sensitive stem cell
      population in the mammary glands. The estrogen negative feedback effect on the
      hypothalamus-pituitary axis and the disruption of steroid biosynthesis and could
      represent an intriguing reason behind this phenomenon. Our results highlight the
      need to evaluate further the increase in progesterone levels in the luteal phase
      in women with breast cancer undergoing COS with letrozole.

PMID- 28742192
TI  - Significance of interleukin and matrix metalloproteinase in patients with
      cognitive dysfunction after single valve replacement.
AB  - OBJECTIVE: To investigate the changes in serum neurological function parameters,
      interleukin (IL) and matrix metalloproteinase (MMP) in patients with cognitive
      dysfunction after single valve replacement. PATIENTS AND METHODS: 51 cases of
      senile patients with cognitive dysfunction after general anesthesia were selected
      as the observation group, and 51 senile patients without cognitive dysfunction
      after general anesthesia were selected as the control group. Serum neurological
      function parameters and IL and MMP levels were examined and compared between the
      two groups. The detected levels were also compared among patients with mild,
      moderate and severe cognitive dysfunction in the observation group. The
      relationship between these serum biomarkers and postoperative cognitive
      dysfunction was analyzed. RESULTS: The serum neurological function parameters and
      IL and MMP levels were significantly higher in the observation group than those
      in the control group. Levels in the severe cognitive impairment group were higher
      than those in the mild and moderate groups, while those in the moderate group
      were higher than those in the mild group. Logistic analysis showed that the above
      indices were closely related to postoperative cognitive dysfunction in elderly
      patients with general anesthesia. The differences between the groups were
      statistically significant (p < 0.05). CONCLUSIONS: Elderly patients with
      postoperative cognitive dysfunction after valve replacement surgery were
      presented with abnormalities in serum neurological function parameters and IL and
      MMP levels. There were significant differences in these indices between patients
      with varying degrees of cognitive dysfunction.

PMID- 28742193
TI  - Relationship between IL-1beta polymorphisms and obstructive sleep apnea syndrome.
AB  - OBJECTIVE: To explore the relationship between obstructive sleep apnea syndrome
      (OSAS) and polymorphism in the IL-1beta gene. PATIENTS AND METHODS: We recruited
      164 OSAS patients to the observation group and 146 healthy people to the control
      group during the same period. Using RFLP (Restriction Fragment Length
      Polymorphism), we detected higher G/G and C/C rates on locus 154 of the IL-1beta
      gene in the OSAS patients compared with the control group. RESULTS: Quantitative
      fluorescence PCR results showed no significant differences in the mRNA expression
      between the OSAS patients and the healthy people. ELISA results showed that
      levels of IL-1beta in people with the G/G and C/C genotypes were lower than those
      with the G/C genotype. The frequencies of T/A and T/T on locus 468 of IL-1beta
      was increased in the OSAS patients compared with the control group. ELISA and
      Western blot results indicated that individuals with the T/T and T/T genotypes at
      locus 468 had lower expression of IL-1beta than those with A/A. CONCLUSIONS: This
      observation suggests that IL-1beta polymorphisms at 154 and 468 contribute to the
      incidence of OSAS, possibly, by altering the protein expression of IL-1beta.

PMID- 28742194
TI  - Dynamic regulation effect of long non-coding RNA-UCA1 on NF-kB in hippocampus of
      epilepsy rats.
AB  - OBJECTIVE: We aimed to discuss the mechanism of occurrence and progression of
      epilepsy through analyzing the expression changes of UCA1 and NF-Kb in temporal
      hippocampus and UCA1 in peripheral blood in rats with epilepsy induced by lithium
      chloride-pilocarpine. MATERIALS AND METHODS: The lithium chloride-pilocarpine
      induced epilepsy rat model was established; 1, 7, 14, 30, and 60 d after status
      epilepticus were selected as the time points of research. The expression levels
      of UCA1 and NF-kB in the hippocampus of rats and UCA1 in peripheral blood were
      detected and analyzed using quantitative Real-time PCR (qRT-PCR). The differences
      and correlations between expression levels of UCA1 and NF-kB at each time point
      of research in experimental group and control group were analyzed statistically.
      RESULTS: Results showed that mRNA expression levels of UCA1 and NF-kB in brain
      tissues in experimental group were higher than those in control group at each
      time point. The change trend of expression levels of UCA1 and NF-kB with time was
      consistent. The expression level of UCA1 in peripheral blood in experimental
      group at each time point was higher than that in control group, and mRNA
      expression level of UCA1 in peripheral blood in experimental group was positively
      correlated with that in brain tissue. CONCLUSIONS: The expressions of UCA1 and NF
      Kb are in the dynamic change in the formation of epilepsy, suggesting that UCA1
      may participate in the pathogenesis of epilepsy, so as to provide a potentially
      feasible new direction for guiding the clinical diagnosis and treatment of
      epilepsy.

PMID- 28742195
TI  - The use of susceptibility-weighted imaging to detect cerebral microbleeds after
      lacunar infarction.
AB  - OBJECTIVE: To study the value of susceptibility-weighted imaging (SWI) technology
      to detect cerebral microbleeds (CMBs) in senile cerebral lacunar infarction
      patients; and to evaluate the complicated cerebral hemorrhage risk after patients
      with CMBs took aspirin, an antiplatelet medication or received anticoagulant
      therapy. PATIENTS AND METHODS: MRI scanning, using GRE-T2*WI, SWI and FSE
      sequences (T1WI, T2WI, and T2FLAIR), was performed on the three groups: (1) a
      cerebral lacunar infarction group; (2) cerebral lacunar infarction with cerebral
      microbleeds (CMBs) group; and (3) a healthy elderly group. A total of 60 cases
      were in each group (180 total patients). In addition, the lacunar infarction
      group and lacunar infarction with CMBs groups were both treated with formal
      antiplatelet or anticoagulant therapy, according to medical guidelines. Patients
      were followed for 12 months, during which time their cerebral hemorrhages and
      post-event effects were observed. The relativity of CMBs, antiplatelet therapy,
      anticoagulant therapy and cerebral hemorrhage transformation was analyzed and
      defined. The two groups of research patients with lacunar infarctions were
      scanned with relevant sequences. RESULTS: The SWI scanning sequence showed the
      highest positive rate of CMBs, followed by GRE-T2*WI and other conventional
      scanning sequences. T1WI, T2WI and T2FLAIR showed a relatively lower positive
      rate of CMBs. In the cerebral lacunar infarction group and healthy elderly group,
      34 cases in the SWI sequence showed 84 positive sites; 18 cases in the GRE-T2*WI
      sequence showed 40 positive sites; 2 cases in the T1WI sequence showed 4 positive
      sites; and 6 cases in the T2WI sequence showed 11 positive sites. After a chi
      squared test, the differences between the sequences were statistically
      significant (p < 0.05). In the lacunar infarction group, 26 cases (43.33%)
      exhibited microbleeding lesions, while the normal control group represented 8
      cases (13.33%). The lacunar infarction group exhibited mild, moderate and severe
      cases, the three types of CMBs. The normal control group only showed mild
      hemorrhaging. The degree of lacunar infarction was significantly related to the
      severity of CMBs (p < 0.05). After patients with CMBs had received formal
      antiplatelet therapy and anticoagulation therapy, one case in the lacunar
      infarction with microbleeds group showed cerebral hemorrhaging, but this had no
      statistical significance (p > 0.05). CONCLUSIONS: The SWI scanning sequence is
      more sensitive than the GRE-T2*WI sequence. The GRE-T2*WI sequence is more
      sensitive than the conventional FSE sequence. SWI is highly sensitive and
      specific to the diagnosis of CMBs. It is an accurate and effective method for the
      analysis and diagnosis of CMBs. If patients with CMBs caused by lacunar
      infarction are treated with antiplatelet and anticoagulant therapy, the risk of
      cerebral hemorrhagic transformation is relatively smaller within 12 months.
      However, this needs to be observed further to define possible long-term risks.

PMID- 28742196
TI  - Sociological histories on epilepsy as "causes for disqualification" stipulated in
      the Japanese Road Traffic Act of 1960 and Revised Road Traffic Act of 2001.
AB  - In the wake of successive cases of fatal accidents caused by patients behind the
      wheel whose driving was likely to be hindered due to paroxysmal diseases,
      including epilepsy, there has been an outcry from victims demanding stricter
      criminal penalties against the perpetrators due to negligence. As a result of
      this action, a revised Road Traffic Act was put into effect in Japan on June 14,
      2013. This act established new penal provisions against any person who provides
      false statements on his/her medical condition(s) when acquiring or renewing a
      driver's license. In this paper, the social circumstances will be introduced
      regarding road traffic in Japan when the Road Traffic Act, the origin of today's
      revised Road Traffic Act, was enacted in 1960. An overview of the reasons behind
      the enactment of the original act will be provided. Additionally, the handling of
      patients with "provisions for disqualification," whose driving is likely to be
      hindered due to paroxysmal diseases, including "epilepsy," will be reviewed. This
      handling attracted repeated controversy during the enactment of the original act
      and will also be reviewed. One significant change in wording from "absolute
      causes for disqualification" in the Road Traffic Act of 1960 to "relative causes
      for disqualification" in the Revised Road Traffic Act of 2001 also will be
      discussed from a medical sociology perspective. Finally, the social status and
      socio-economic position of drivers with paroxysmal diseases, as it pertains to
      influences on lawmakers, will be discussed.

PMID- 28742197
TI  - MiR-24 alleviates cardiomyocyte apoptosis after myocardial infarction via
      targeting BIM.
AB  - OBJECTIVE: Ischemia hypoxia induces cardiomyocyte (CM) apoptosis in the process
      of acute myocardial infarction (AMI). It was showed that pro-apoptosis factor BIM
      participates in regulating tumor cell apoptosis under ischemia or hypoxia
      condition, while its role in CM apoptosis after AMI is still unclear. It was
      revealed that miR-24 expression was significantly reduced in myocardial tissue
      after AMI. Bioinformatics analysis exhibits that miR-24 is targeted to the 3'-UTR
      of BIM. This study aims to investigate the role of miR-24 in mediating BIM
      expression and CM apoptosis. PATIENTS AND METHODS: Dual-luciferase assay was used
      to confirm the targeted regulation between miR-24 and BIM. Cells were cultured
      under ischemia hypoxia for 12 h after transfection for 48 h. Cell apoptosis was
      tested by using flow cytometry. The caspase activity was detected by using
      spectrophotometry. Wistar rats were divided into four groups, including Sham,
      AMI, AMI + agomir-control, and AMI + agomir-24 groups. Cardiac function was
      evaluated by using echocardiography. CM apoptosis was determined by using TUNEL.
      Infarction area was measured by using evans blue staining. MiR-24 targeted
      suppressed BIM expression. RESULTS: MiR-24 mimic and/or si-BIM transfection
      significantly declined the BIM expression, inhibited caspase-9 and caspase-3
      activities, and reduced cell apoptosis in H9C2 cells. MiR-24 expression was
      decreased, while BIM levels were up-regulated in myocardium after AMI. Agomir-24
      injection down-regulated the BIM expression in myocardium, reduced CM apoptosis,
      narrowed infarction area, and improved cardiac function in rats. CONCLUSIONS: MiR
      24 was reduced, whereas BIM was enhanced in the CM after AMI. MiR-24 up
      regulation plays a critical role in decreasing BIM expression, reducing CM
      apoptosis, and improving cardiac function after AMI.

PMID- 28742198
TI  - Methionine synthase A2756G polymorphism and lymphoma risk: a meta-analysis.
AB  - OBJECTIVE: The association between methionine synthase (MS) A2756G polymorphism
      and lymphoma risk was studied with conflicting results. The present meta-analysis
      aimed to investigate the overall association between MS A2756G polymorphism and
      lymphoma risk. MATERIALS AND METHODS: We searched PubMed and Embase databases
      until March 30, 2017, for articles that assessed the association between MS
      A2756G polymorphism and lymphoma risk. Statistical analyses were performed using
      the Revman 5.0 software. RESULTS: A total of 14 articles involving 4,156 cases
      and 6,407 controls were included in this meta-analysis. Combined analysis
      revealed no association between this polymorphism and lymphoma susceptibility (OR
      = 0.92, 95% CI: 0.74-1.16, p = 0.50 for GG vs. GA+AA). Subgroup analysis by
      ethnicity showed decreased lymphoma risk with the MS A2756G gene polymorphism
      among Caucasians in GG+GA vs. AA and G vs. A models, but not among Asians.
      Subgroup analysis by disease type suggested that GG homozygous and G alleles were
      not associated with risks of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL),
      the subtype of NHL including the diffuse large B-cell lymphoma and follicular
      lymphoma. CONCLUSIONS: The results in this meta-analysis suggest no association
      between the MS A2756G polymorphism and lymphoma risk; however, the GG homozygous
      and G alleles could decrease the lymphoma risk in Caucasians.

PMID- 28742199
TI  - Cyramza induces apoptosis of HCC4006 cell by affecting the level of Bcl-w.
AB  - OBJECTIVE: Lung cancer seriously threats to patient's life and health. Cyramza is
      a therapeutic drug for inhibition of vessel formation and growth in clinical
      practice. The aim of this study was to investigate the effect of cyramza on
      growth and apoptosis of non-small lung cancer HCC4006 and explore the related
      mechanisms. MATERIALS AND METHODS: Cell viability and apoptosis were examined by
      MTT assay and flow cytometry, respectively. Western blot was employed to examine
      the effect of cyramza on the apoptotic protein Bcl-w. After that Bcl-w knockdown
      and overexpression were respectively fulfilled by Bcl-w siRNA and plasmid
      transfection, effects of cyramza on cell apoptosis were determined by Western
      blot. RESULTS: Cyramza inhibited the cell growth and induced the cell apoptosis
      in HCC4006 cells, which was mediated by downregulation of Bcl-w level. Bcl-w
      knockdown and overexpression could increase and decrease the effect of cyramza on
      cell apoptosis, respectively. CONCLUSIONS: Cyramza induced the apoptosis of non
      small lung cancer cell line HCC4006 via the downregulation of Bcl-w.

PMID- 28742200
TI  - Hypoxia promotes epithelial-mesenchymal transition of hepatocellular carcinoma
      cells via inducing Twist1 expression.
AB  - OBJECTIVE: To investigate whether hypoxia microenvironment induced hepatocellular
      carcinoma cells SMMC-7721 epithelial-mesenchymal transition (EMT) and to explore
      the underlying molecular mechanism. MATERIALS AND METHODS: In this study, SMMC
      7721 cells were cultured under normoxia and hypoxia conditions, respectively. RT
      PCR and Western blot were used to monitor the expression level of EMT-related
      markers, E-cadherin, and vimentin, as well as hypoxia inducible factor-1alpha
      (HIF-1alpha) and Twist1. Then we performed the transwell invasion assays to
      detect the ability of cell invasion. RESULTS: The results demonstrated that
      hypoxia micro-environment could induce hepatocellular carcinoma cells SMMC-7721
      EMT and enhance the cell invasion ability. Furthermore, knockdown of Twist1 by
      using specific siRNA could reverse hypoxia-induced EMT process. CONCLUSIONS:
      Hypoxia promotes hepatocellular carcinoma cells SMMC-7721 EMT by upregulating the
      expression of Twist1.

PMID- 28742201
TI  - The study on expression of CIAPIN1 interfering hepatocellular carcinoma cell
      proliferation and its mechanisms.
AB  - OBJECTIVE: Liver cancer is one of the common gastrointestinal cancers. This study
      was designed to investigate the effect of the cytokine-induced apoptosis
      inhibitor 1 (CIAPIN1) on hepatocellular carcinoma cell proliferation and
      invasion. MATERIALS AND METHODS: To establish a low and high expression of
      CIAPIN1 in hepatoma cell lines, pGPU6/GFP/Neo and CIAPIN1 siRNA vectors were
      constructed. The growth curve of liver cancer cells with a low and high
      expression of CIAPIN1 was measured by MTT assay and colony formation in soft. The
      effect of overexpression and inhibition of CIAPIN1 on the expressions of cell
      cycle proteins Cyclin D1, CDK2, CDK4, and Cyclin E were detected by western blot.
      RESULTS: As compared with the low expression group, the cells in CIAPIN1 high
      expression group showed a significant decrease in proliferation (p < 0.05). In
      addition, the colony-forming ability of cells with high expression of CIAPIN1 was
      decreased significantly (p < 0.01). Furthermore, the expressions of Cyclin D1
      CDK2, CDK4, and Cyclin E in high expression group were significantly increased (p
      < 0.01). CONCLUSIONS: CIAPIN1 played an important role in the proliferation of
      liver cancer cells through increasing the expressions of cell cycle related
      proteins Cyclin D1, CDK2, CDK4, and Cyclin E.

PMID- 28742202
TI  - Does the age affect the efficacy of angiogenesis inhibitors in ovarian cancer? A
      meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: There are limited data on the role of angiogenesis inhibitors (AIs) in
      the treatment of elderly patients with ovarian cancer. We aim to assess the
      overall efficacy of AIs-containing regimens in the treatment of ovarian cancer in
      this patients group. MATERIALS AND METHODS: Databases and abstracts presented
      meetings up to November 2016 were searched to identify relevant studies.
      Prospective randomized controlled trials (RCTs) investigating therapies with or
      without AIs in elderly patients with ovarian cancer were included in the present
      study. Statistical analyses were conducted by using Version 2 of the
      Comprehensive meta-analysis program. RESULTS: A total of 1901 elderly patients
      with ovarian cancer from six RCTs were identified for analysis. The pooled
      results demonstrated that the use of AIs-containing regimens significantly
      improved PFS (HR 0.70, 95% CI: 0.63-0.78, p < 0.001) when compared to non-AIs
      containing regimens, but not for OS (HR 1.07, 95% CI: 0.86-1.34, p = 0.54).
      Subgroup analyses favored greater benefit for PFS (HR 0.60, p < 0.001) in second
      line settings compared to first-line settings (HR 0.75, p < 0.001). No
      publication bias was detected by Begg's and Egger's tests for PFS. CONCLUSIONS:
      The findings of this work suggest that the use of AIs in the treatment of elderly
      patients with ovarian cancer offers an improved PFS, but not for OS. Further
      studies are needed to clearly set the role of AIs in ovarian cancer in this
      patients group.

PMID- 28742203
TI  - Expression levels and roles of EMC-6, Beclin1, and Rab5a in the cervical cancer.
AB  - OBJECTIVE: This study is to investigate the role of EMC-6 in the pathogenesis of
      cervical cancer, especially concerning its relationship with autophagy. PATIENTS
      AND METHODS: Totally 100 invasive cervical cancer, 80 cervical intraepithelial
      neoplasia (CIN), and 80 normal cervical tissue samples were obtained. Expression
      levels of EMC-6, Beclin1, and Rab5a in the tissues were detected by
      immunohistochemistry. RESULTS: Our results showed that positive staining of EMC-6
      was mainly located in the nucleus. Compared with the normal cervical tissue, the
      positive rates of EMC-6 were significantly increased in the CIN and cervical
      cancer tissues. Moreover, the EMC-6 positive rate in the CIN tissue was higher
      than the cervical cancer tissue. No significant association was observed between
      the expression levels of EMC-6 and the clinicopathological features of cervical
      cancer, including age, FIGO staging, tumor size, tumor type, histological type,
      cell differentiation, and lymph node metastasis. Compared with the normal
      cervical tissue, the positive rate of Beclin1 in the CIN tissue was significantly
      declined, which was further significantly down-regulated in the cervical cancer
      tissue. However, the positive rate of Rab5a in the CIN tissue was significantly
      higher than the normal cervical tissue. Moreover, compared with the normal
      cervical and CIN tissues, the positive rate of Rab5a in the cervical cancer
      tissue was further significantly increased. EMC-6 was not associated with Beclin1
      and Rab5a. CONCLUSIONS: The expression level of EMC-6 is significantly elevated
      in cervical cancer, without significant correlation with Beclin1 and Rab5a. These
      findings might contribute to the understanding of the pathogenesis of cervical
      cancer and the involved role of EMC-6.

PMID- 28742204
TI  - MiR-144 functions as tumor suppressor by targeting PIM1 in gastric cancer.
AB  - OBJECTIVE: Gastric cancer (GC) is one of the most prevalent types of malignant
      disease Worldwide. Mounting evidence has demonstrated the involvement of miRNAs
      in the development of GC. One of these miRNAs, miR-144 has been found aberrantly
      expressed in a variety of human malignancies. PATIENTS AND METHODS: GC tissues
      were collected from patients, and the level of miR-144 was determined by qRT-PCR.
      GC cell lines SGC7901 and AGS were used as model cell lines and the anti-tumor
      effect of miR-144 in both cells were examined. The level of miR-144 was restored
      in GC cells using miR-144 mimic. Moreover, the target gene of miR-144 wad
      identified. RESULTS: In this study, our results showed that low miR-144 level
      significantly correlated with lymph node metastasis stage, TNM stage and
      differentiation degree. In addition, we found that miR-144 acted as a tumor
      suppressor in GC. Moreover, our findings showed that miR-144 exerted an anti
      tumor effect by directly targeting RLIP76. CONCLUSIONS:   miR-144 acts as a tumor
      suppressor in GC and it is a potential therapeutic target for GC treatment.

PMID- 28742205
TI  - Up-regulation of long non-coding RNA PCAT-1 correlates with tumor progression and
      poor prognosis in gastric cancer.
AB  - OBJECTIVE: Long non-coding RNAs (lncRNAs), emerging non-coding RNAs, have been
      proved to serve as a critical role in the proliferation, metastasis apoptosis of
      gastric cancer. However, the potential biological role PCAT-1 in gastric cancer
      (GC) remains undefined. The present study aimed to investigate the expression and
      clinical significance of PCAT-1 in GC. PATIENTS AND METHODS: The expression of
      PCAT-1 was detected with a quantitative Real-time PCR assay. The association
      between PCAT-1 expression and clinicopathological factors, as well as survival
      rates, was analyzed. Cox proportional-hazards regression analysis was applied in
      order to estimate univariate and multivariate hazard ratios for overall survival.
      Then, effects of PCAT-1 on the biological behavior of GC cells were investigated.
      RESULTS: We found that PCAT-1 expression was elevated in GC tissues and cell
      lines, and PCAT-1 levels were highly positively correlated with invasion depth (p
      < 0.001), TNM stages (p < 0.001) and lymphatic metastasis (p = 0.003). The
      biological function of PCAT-1 was explored and the results showed silencing of
      PCAT-1 could suppress cell proliferation, migration and invasion in vitro. Kaplan
      Meier analysis demonstrated that increased PCAT-1 expression contributed to poor
      overall survival (OS) (p < 0.01). Furthermore, in a multivariate Cox model, our
      results showed that PCAT-1 expression was an independent poor prognostic factor
      for OS in GC. CONCLUSIONS: Our finding suggested that PCAT-1 may have potential
      roles as a biomarker and/or a therapeutic target in gastric cancer.

PMID- 28742206
TI  - Bioinformatics analysis of RNA-seq data revealed critical genes in colon
      adenocarcinoma.
AB  - OBJECTIVE: RNA-seq data of colon adenocarcinoma (COAD) were analyzed with
      bioinformatics tools to discover critical genes in the disease. Relevant small
      molecule drugs, transcription factors (TFs) and microRNAs (miRNAs) were also
      investigated. MATERIALS AND METHODS: RNA-seq data of COAD were downloaded from
      The Cancer Genome Atlas (TCGA). Differential analysis was performed with package
      edgeR. False positive discovery (FDR) < 0.05 and |log2 (fold change)|>1 were set
      as the cut-offs to screen out differentially expressed genes (DEGs). Gene
      coexpression network was constructed with package Ebcoexpress. GO enrichment
      analysis was performed for the DEGs in the gene coexpression network with DAVID.
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was
      also performed for the genes with KOBASS 2.0. Modules were identified with MCODE
      of Cytoscape. Relevant small molecules drugs were predicted by Connectivity map.
      Relevant miRNAs and TFs were searched by WebGestalt. RESULTS: A total of 457
      DEGs, including 255 up-regulated and 202 down-regulated genes, were identified
      from 437 COAD and 39 control samples. A gene coexpression network was constructed
      containing 40 DEGs and 101 edges. The genes were mainly associated with collagen
      fibril organization, extracellular matrix organization and translation. Two
      modules were identified from the gene coexpression network, which were implicated
      in muscle contraction and extracellular matrix organization, respectively.
      Several critical genes were disclosed, such as MYH11, COL5A2 and ribosomal
      proteins. Nine relevant small molecule drugs were identified, such as scriptaid
      and STOCK1N-35874. Accordingly, a total of 17 TFs and 10 miRNAs related to COAD
      were acquired, such as ETS2, NFAT, AP4, miR-124A, MiR-9, miR-96 and let-7.
      CONCLUSIONS: Several critical genes and relevant drugs, TFs and miRNAs were
      revealed in COAD. These findings could advance the understanding of the disease
      and benefit therapy development.

PMID- 28742207
TI  - SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells.
AB  - OBJECTIVE: JAK-STAT3 signaling pathway widely participates in cell proliferation
      and apoptosis. Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator
      of JAK-STAT3. SOCS3 downregulation is associated with drug resistance in breast
      cancer and leukemia. However, its role in bladder cancer drug resistance is still
      unclear. This study established ADM resistant bladder cancer cell model to
      investigate the role of SOCS3-JAK/STAT3 signaling pathway ADM resistance.
      MATERIALS AND METHODS: ADM drug resistant cell line T24/ADM was established.
      SOCS3, p-JAK2, p-JAK3, and Bcl-2 expressions in T24/ADM, T24, and HBEC cells were
      compared. Cell proliferation and apoptosis were evaluated by flow cytometry.
      T24/ADM cells were divided into five groups, including control, pSicoR-blank,
      pSicoR-SOCS3, FLLL32, and pSicoR-SOCS3 + FLLL32 groups. Cell proliferation was
      determined by EdU staining. RESULTS: SOCS3 was reduced, while p-JAK2, p-STAT3,
      and Bcl-2 expressions upregulated in T24 cells compared with HBEC cells. T24/ADM
      cells exhibited lower SOCS3, higher p-JAK2, p-STAT3, and Bcl-2 levels than T24
      cells. Cell apoptosis was higher, whereas cell proliferation was weaker in T24
      cells compared with T24/ADM cells. SOCS3 overexpression and/or FLLL32 treatment
      significantly downregulated p-JAK2, p-STAT3, and Bcl-2 expressions, attenuated
      cell proliferation, and elevated sensitivity to ADM induced cell apoptosis.
      CONCLUSIONS: SOCS3 reduction was associated with bladder cancer sensitivity to
      ADM. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity,
      declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis,
      and enhanced ADM sensitivity in T24 cells.

PMID- 28742208
TI  - Effects of microRNA-21 targeting PITX2 on proliferation and apoptosis of
      pituitary tumor cells.
AB  - OBJECTIVE: Expression of pituitary homeobox 2 (PITX2) is significantly elevated
      in pituitary adenoma tissues, which also has lower microRNA (miR)-21 expression,
      indicating possible tumor-suppression role of miR-21. Bio-informatics analysis
      revealed targeting onto 3'-UTR of PITX2 by miR-21. This study aims to investigate
      the role of miR-21/PITX2 expression in proliferation and apoptosis of pituitary
      adenoma cells and pathogenesis. PATIENTS AND METHODS: A total of 48 pituitary
      adenoma samples were collected in parallel with 12 normal brain tissues and were
      recruited in this study. Flow cytometry was employed to test Ki-67 expression and
      apoptosis. Expressions of miR-21 and PITX2 were compared, along with their
      targeted relationship by dual-luciferase reporter assay. Cultured HP75 cells were
      transfected with miR-21 mimic and/or si-PITX2. Caspase-3 activity was further
      quantified, followed by flow cytometry for apoptosis. MiR-21, cleaved caspase-3
      and PITX2 expressions were tested. RESULTS: Invasive pituitary adenoma tissues
      had significantly higher Ki-67 and PITX2, and lower miR-21 expressions or
      apoptosis than non-invasive tumors. MiR-21 targeted 3'-UTR of PITX2 gene to
      inhibit its expression. Elevated miR-21 and/or silencing PITX2 significantly
      depressed PITX2 expression in HP75 cells, potentiating caspase-3 activity,
      decreasing cell proliferation and facilitating apoptosis. CONCLUSIONS: MiR-21 was
      down-regulated while PITX2 was up-regulated in pituitary adenoma tissues. MiR-21
      can inhibit pituitary adenoma cell HP75 proliferation and facilitate apoptosis
      via inhibiting PITX2 expression.

PMID- 28742209
TI  - The expression significance of serum MiR-21 in patients with osteosarcoma and its
      relationship with chemosensitivity.
AB  - OBJECTIVE: To investigate the expression level of serum microRNA-21 (miR-21) in
      69 patients with osteosarcoma, to analyze the changes in miR-21 expression in the
      serum and tumor tissues before and after chemotherapy in patients with
      osteosarcoma, and to investigate the relationship between the expression of serum
      miR-21 in patients with osteosarcoma and chemosensitivity. PATIENTS AND METHODS:
      Real-time polymerase chain reaction (RT-PCR) was used to detect the expression
      level of serum miR-21 in 69 patients with osteosarcoma before and after
      chemotherapy, and analyze the relationship between the expression of miR-21 with
      tumor necrosis grading and chemosensitivity. The expression level of programmed
      cell death protein 4 (PDCD4) in tumor tissues of patients with osteosarcoma
      before and after chemotherapy was detected by Western blot. RESULTS: The
      expression level of serum miR-21 in patients with osteosarcoma was significantly
      higher than that in normal control subjects. The expression of serum miR-21
      before and after chemotherapy was positively correlated with the expression of
      miR-21 in the corresponding tissues. In the group where chemotherapy was
      effective (the effective group), expression levels of miR-21 in patients with
      osteosarcoma before and after chemotherapy were significantly different. After
      chemotherapy, the expression level of target genes of miR-21 was increased, and
      the follow-up results showed that the 5-year survival rate was relatively higher
      after surgery. CONCLUSIONS: The expression level of serum miR-21 in patients with
      osteosarcoma is closely related to the therapeutic effects of osteosarcoma, which
      can be used as one of the potential biomarkers and therapeutic targets for the
      diagnosis and prediction of osteosarcoma.

PMID- 28742210
TI  - Clinical research on correction of ankle arthritis-related factor levels via
      urea.
AB  - OBJECTIVE: To investigate the reliability of urea as the internal reference of
      ankle irrigating fluid in correction of synovial fluid and related factor
      concentration dilution times, and to further determine the factor expression
      level in synovial fluid. PATIENTS AND METHODS: A total of 91 patients, including
      20 cases of non-posterior median foot lesions and 71 cases of unilateral ankle
      osteoarthritis, were enrolled in this study. AOFAS score, Takakura staging and
      visual analogue pain scale were given; the venous blood was collected and the
      ankle fluid and irrigating fluid were obtained from the affected side via
      puncture. The urea in serum, synovial fluid and irrigating fluid was quantified
      using an AU5800 biochemical instrument (Beckman Coulter). Statistical analysis
      was performed for the correlation between urea in serum and synovial fluid; the
      levels of TNF-alpha, IL-1beta, IL-6, IGF-1 and HELIX-II in irrigating fluid
      quantified by enzyme linked immunosorbent assay (ELISA) were further corrected.
      RESULTS: There was a good linear relationship between urea contents in synovial
      fluid and serum (R2=0.89), and the regression slope was 0.927. The levels and
      ratio of urea in serum and synovial fluid were independent of Takakura staging or
      pain degree. The expressions of IL-1beta (p=0.000), IGF-1 (p=0.000) and HELIX-II
      (p=0.010) were significantly increased in synovial fluid in patients with ankle
      osteoarthritis. There was no significant difference in expression of IL-1beta
      (p=0.514), and TNF-alpha was not detected in synovial fluid. CONCLUSIONS: This
      study confirmed the dynamic stability of urea in the ankle fluid, and it is not
      affected by the progression of arthritis, age and other factors, which is the
      standard internal reference of correcting ankle irrigating fluid dilution times.
      The occurrence mechanism of ankle osteoarthritis may be different from that of
      other osteoarthritis, and IL-6 and IGF-1 are associated with the progression of
      the disease. Increased HELIX-II is an independent factor of predicting cartilage
      injury.

PMID- 28742211
TI  - Targeting of miR-20a against CFLAR to potentiate TRAIL-induced apoptotic
      sensitivity in HepG2 cells.
AB  - The article "Targeting of miR-20a against CFLAR to potentiate TRAIL-induced
      apoptotic sensitivity in HepG2 cells" by Y. Wang, Y.-R. Zhao, A.-Y. Zhang, J. Ma,
      Z.-Z. Wang, X. Zhang, published in Eur Rev Med Pharmacol Sci 2017; 21 (9): 2087
      2097 has been withdrawn.

PMID- 28742212
TI  - Relevant researches on chronic viral myocarditis (CVMC) in children, complicated
      with arrhythmia and thyroid hormone level.
AB  - OBJECTIVE: To analyze the correlation between chronic viral myocarditis (CVMC) in
      children, complicated with arrhythmia and thyroid hormone level. PATIENTS AND
      METHODS: 60 patients with CVMC complicated with arrhythmia were continuously
      selected (course of disease > 3 months) and they are were diagnosed with
      arrhythmia by the routine 18-lead electrocardiogram and 24-hour Holter; the
      average follow-up time is about 2 years, during which the left ventricular end
      diastolic diameter (LVEDd), left ventricular ejection fraction (LVEF), the
      occurrence rate of malignant arrhythmia events, immune state of T cell and
      thyroid hormone level (FT3, FT4, TSH, TGAb and TPOAb) were compared. RESULTS:
      Among the selected 60 patients, 18 patients (30.0%) who were suffering from
      malignant arrhythmia have been taken as the observation group. When compared with
      the control group, the standard deviation normal to normal intervals (SDNN),
      LVEF, CD4 and CD4/CD8 were reduced and LVEDd and CD8 were increased in the
      observation group; the difference has statistical significance (p < 0.05). When
      compared with the control group, FT3 and FT4 are significantly reduced and TSH,
      thyroglobulin antibody TGAB and thyroid peroxidase antibodies (TPOAb) are
      significantly increased; the difference has statistical significance (p < 0.05).
      According to the logistic regression analysis, we can conclude that: SDNN, FT3,
      FT4, TSH, TGAb and TPOAb are the independent risk factors of malignant arrhythmia
      (p < 0.05). CONCLUSIONS: Thyroid hormones and antibody level are helpful to the
      prognosis of malignant arrhythmia resulting from children chronic VMC complicated
      with arrhythmia complications.

PMID- 28742213
TI  - Derivatization agents for electrochemical detection in amino acid, peptide and
      protein separations: The hidden electrochemistry?
AB  - In proteomics and clinical analysis, LIF and MS are the most used detectors
      coupled to separation techniques. MS offers good sensitivity and analyte
      identification ability but, as counterbalance, it is expensive and it needed
      background electrolytes compatible with mass spectrometers. LIF detection offers
      the highest sensitivity but, in general, proteins, peptides and amino acids are
      not fluorescents so it is necessary the use of fluorescence tags. This fact
      hindered the potential sensitivity of LIF detection due to the difficulty of
      labeling analytes at extremely low concentrations. In the context of micro- and
      nanofluidics, electrochemical detection (ED) is an excellent alternative to LIF
      and MS because it offers several advantages such as easy miniaturization, simpler
      methods, lower cost and high sensitivity in spite of decreasing the electrode
      size and sample volume. Among ED techniques, amperometric detection (AD and PAD)
      are the most used. The problem is that the sensitivity is not enough for the
      majority of proteomics and clinical applications. To overcome this handicap,
      electrochemical derivatization reagents have been employed with excellent results
      allowing limits of detection in nanomolar range. This review surveys all papers
      related to electrochemical derivatization reagents employed for amino acids,
      peptides and proteins in separation techniques. Additionally, we highlight the
      possibilities of this electrochemical tags in the context of micro- and nano-
      separation techniques and showed potential electrochemical tags which could be
      employed in the near future for proteomics applications.

PMID- 28742214
TI  - Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant
      with neural tube defects.
AB  - Folate and vitamin B12 are needed for the proper embryo-fetal development
      possibly through their interacting role in the 1-carbon metabolism. Folate
      fortification reduces the prevalence of complex birth defects, and more
      specifically neural tube defects (NTDs). GIF and FUT2 are 2 genes associated with
      the uptake and blood level of vitamin B12. We evaluated GIF and FUT2 as
      predictors of severe birth defects, in 183 aborted fetuses compared with 375
      healthy newborns. The GIF290C allele frequency was estimated to 0.4% in healthy
      newborns and to 8.1% in NTD fetuses (odds ratio 17.8 [95% confidence interval CI:
      4.0-77.6]). The frequency of FUT2 rs601338 secretor variant was not different
      among groups. The GIF 290C heterozygous/FUT2 rs601338 secretor variant combined
      genotype was reported in 6 of the 37 NTD fetuses, but not in other fetuses and
      healthy newborns (P < .0001). This GIF/FUT2 combined genotype has been previously
      reported in children with congenital gastric intrinsic factor (GIF) deficiency,
      with respective consequences on B12 binding activity and GIF secretion. In
      conclusion, a genotype reported in congenital GIF deficiency produces also severe
      forms of NTD. This suggests that vitamin B12 delivery to neural tissue by the
      CUBN/GIF pathway could play a role in the neural tube closure mechanisms.

PMID- 28742215
TI  - Complementary and Alternative Medicine Use Among US Adults With Headache or
      Migraine: Results from the 2012 National Health Interview Survey.
AB  - BACKGROUND: Given the safety concerns regarding pharmacological agents, and the
      considerable impact of headache and migraine on the sufferer's quality of life,
      many people seek other treatment options beyond conventional medication and care
      to address their symptoms; this includes complementary and alternative medicine
      (CAM). Some CAM interventions have shown promising results in clinical trials of
      headache and migraine management. Nonetheless, there has been little research
      exploring the reasons for using CAM, and the types of CAM used, among this
      population. OBJECTIVE: The study aimed to answer the following questions: (1)
      Which CAM modalities are used most frequently among migraine/headache sufferers?
      and (2) What are the self-reported reasons for CAM use among migraine/headache
      sufferers? METHODS: This secondary analysis of data from the 2012 U.S. NHIS (a
      national cross-sectional survey) examined the use of CAM among migraine/headache
      sufferers, including the main reasons related to CAM use. Data were weighted and
      analyzed using STATA 14.0. RESULTS: The sample of 34,525 adults included 6558
      (18.7%) headache/migraine sufferers. Of the headache/migraine sufferers, a
      substantial proportion (37.6%, n = 2427) used CAM for various conditions;
      however, CAM use specifically for headache/migraine was much less prevalent
      (3.3%, n = 216). Of those who used CAM for headache/migraine, about half used CAM
      in conjunction with prescription (47.8%, n = 100) or over-the-counter medication
      (55.1%, n = 113). As severity of headache/migraine increased so did the
      likelihood of using CAM (severe migraine odds ratio [OR] = 2.32; 95% confidence
      interval [CI]: 1.41, 3.82; both recurring headache/severe migraine OR = 3.36; 95%
      CI: 2.08, 5.43; when compared to those with recurring headache only). The most
      frequently used CAM modality among all headache/migraine sufferers (N = 6558) was
      manipulative therapy (22.0%, n = 1317), herbal supplementation (21.7%, n = 1389)
      and mind-body therapy (17.9%, n = 1100). The top 3 reasons for using CAM for
      headache were general wellness (28.7%, n = 60/209), improving overall health
      (26.8%, n = 56/209), and reducing stress (16.7%, n = 35/209). CONCLUSIONS:
      Although CAM is used by many sufferers of headache/migraine, the use of CAM
      specifically for the treatment of headache/migraine is relatively low in the
      United States. The study also assesses the key differences of CAM use among
      headache/migraine sufferers in NHIS 2012 compared with those in NHIS 2007, and
      identifies shortfalls in the evidence-base of several CAM modalities used by U.S.
      adults for headache/migraine. This information may assist health providers and
      consumers in making informed decisions about the safest and most appropriate
      approach to managing headache/migraine.

PMID- 28742216
TI  - The fetuses-at-risk approach: survival analysis from a fetal perspective.
AB  - Several phenomena in contemporary perinatology create challenges for analyzing
      pregnancy outcomes. These include recent increases in iatrogenic delivery at late
      preterm and early term gestation, which are incongruent with the belief that
      stillbirth and neonatal death risks decrease exponentially with advancing
      gestational age. Perinatal epidemiologists have also puzzled over the paradox of
      intersecting birthweight-specific and gestational age-specific perinatal
      mortality curves for decades. For example, neonatal mortality rates among preterm
      infants of women who smoke are substantially lower than neonatal mortality rates
      among preterm infants of non-smoking women, whereas the reverse pattern occurs at
      term gestation. This mortality crossover is observed across several contrasts
      (for example, women with hypertensive disorders of pregnancy vs. normotensive
      women, older vs. younger women, twins vs. singletons) and outcomes (stillbirth,
      neonatal death, sudden infant death syndrome and cerebral palsy), and
      irrespective of how advancing "maturity" is defined (birthweight or gestational
      age). One approach proposed to address and explain these unexpected phenomena is
      the fetuses-at-risk model. This formulation involves a reconceptualization of the
      denominator for perinatal outcome rates from births to surviving fetuses. In this
      overview of the fetuses-at-risk model, we discuss the central tenets of the
      births-based and the fetuses-based formulations. We also describe the extension
      of the fetuses-at-risk approach to outcomes into and beyond the neonatal period
      and to a multivariable adaptation. Finally, we provide a substantive context by
      discussing biological mechanisms underlying the fetuses-at-risk model and
      contemporary obstetric phenomena that are better understood from that model than
      from one based on births.

PMID- 28742217
TI  - The inflammatory cytokine interferon-gamma inhibits sortilin-1 expression in
      hepatocytes via the JAK/STAT pathway.
AB  - Sortilin-1, a receptor of the VPS10p family, has been associated with
      cardiovascular disease in genome-wide association studies. It is implicated in
      lipoprotein metabolism, secretion of proprotein convertase subtilisin/kexin type
      9 (PCSK9) and secretion of inflammatory cytokines. However, its own regulation
      remains unclear. Chronic inflammation is a hallmark of atherosclerosis and the
      absence of regulatory T (Treg) cells is associated with reduced protein
      expression of sortilin-1 in the liver. Therefore, we postulated that mediator(s)
      of inflammation known to be downregulated by Treg cells may modulate sortilin-1
      expression. In this study, we identify interferon-gamma (IFN-gamma) as the key
      inflammatory mediator controlling sortilin-1 levels. In vitro cultures of murine
      hepatocytes cell line and in silico experiments showed that the transcription
      factor Signal transducer and activator of transcription 1 was activated and bound
      to the Sort-1 gene upon IFN-gamma treatment. This reduced the expression of
      sortilin-1, while disrupting the IFN-gamma signaling pathway prevented the
      effect. These data unravel an intricate mechanism by which inflammation modulates
      receptors involved in lipoprotein turnover.

PMID- 28742218
TI  - If the coping fits, use it: Preadolescent recent stress exposure differentially
      predicts post-TSST salivary cortisol recovery.
AB  - This study examined recent stress exposure and effortful coping effects on
      salivary cortisol (sC) response patterns in preadolescent boys and girls (N =
      121, Mage  = 10.60 years). Children were exposed to the Trier Social Stress Test
      (TSST) and one of two randomly assigned, post-TSST coping conditions: distraction
      and avoidance. Piecewise growth multilevel modeling did not link children's
      recent stressful life events or hair cortisol (hC) levels to sC reactivity,
      though each interacted with coping condition to predict sC recovery patterns.
      Children with elevated life stressor and hC levels demonstrated protracted sC
      recovery when primed with distraction, yet more efficient sC recovery when primed
      with avoidance. Findings challenge assumptions about universally "good" and "bad"
      coping by highlighting contexts where each succeed and fail in helping children
      manage acute stress physiology.

PMID- 28742219
TI  - Model-free scoring system for risk prediction with application to hepatocellular
      carcinoma study.
AB  - There is an increasing need to construct a risk-prediction scoring system for
      survival data and identify important risk factors (e.g., biomarkers) for patient
      screening and treatment recommendation. However, most existing methodologies
      either rely on strong model assumptions (e.g., proportional hazards) or only
      handle binary outcomes. In this article, we propose a flexible method that
      simultaneously selects important risk factors and identifies the optimal linear
      combination of risk factors by maximizing a pseudo-likelihood function based on
      the time-dependent area under the receiver operating characteristic curve. Our
      method is particularly useful for risk evaluation and recommendation of optimal
      subsequent treatments. We show that the proposed method has desirable theoretical
      properties, including asymptotic normality and the oracle property after variable
      selection. Numerical performance is evaluated on several simulation data sets and
      an application to hepatocellular carcinoma data.

PMID- 28742220
TI  - Dissecting functions of SEPALLATA-like MADS box genes in patterning of the
      pseudanthial inflorescence of Gerbera hybrida.
AB  - The pseudanthial inflorescences of the sunflower family, Asteraceae, mimic a
      solitary flower but are composed of multiple flowers. Our studies in Gerbera
      hybrida indicate functional diversification for SEPALLATA (SEP)-like MADS box
      genes that often function redundantly in other core eudicots. We conducted
      phylogenetic and expression analysis for eight SEP-like GERBERA REGULATOR OF
      CAPITULUM DEVELOPMENT (GRCD) genes, including previously unstudied gene family
      members. Transgenic gerbera plants were used to infer gene functions. Adding to
      the previously identified stamen and carpel functions for GRCD1 and GRCD2, two
      partially redundant genes, GRCD4 and GRCD5, were found to be indispensable for
      petal development. Stepwise conversion of floral organs into leaves in the most
      severe RNA interference lines suggest redundant and additive GRCD activities in
      organ identity regulation. We show conserved and redundant functions for several
      GRCD genes in regulation of flower meristem maintenance, while functional
      diversification for three SEP1/2/4 clade genes in regulation of inflorescence
      meristem patterning was observed. GRCD genes show both specialized and
      pleiotropic functions contributing to organ differentiation and flower meristem
      fate, and uniquely, to patterning of the inflorescence meristem. Altogether, we
      provide an example of how plant reproductive evolution has used conserved genetic
      modules for regulating the elaborate inflorescence architecture in Asteraceae.

PMID- 28742221
TI  - Effects of concentrated and dephytinized wheat bran and rice bran addition on
      bread properties.
AB  - : Wheat bran and rice bran were concentrated in terms of dietary fiber and were
      dephytinized by two different methods (fermentation and hydrothermal). Untreated,
      concentrated, concentrated-dephytinized by fermentation method, and concentrated
      dephytinized by hydrothermal method bran samples were each incorporated into
      flour at levels of 0, 10, 15, and 20%, and their effects on bread properties were
      investigated. Unprocessed wheat bran and rice bran addition decreased the volume
      yield, and the specific volume of the bread depends on the incorporation level. A
      further decrease was observed with the addition of concentrated bran. However,
      the dephytinization treatments slightly improved these values. The same pattern
      was observed for the total number of cells and the total cell area of bread
      crumbs. Both wheat bran and rice bran were observed to cause a darker crumb
      color, and the effects of bran samples on crumb color were more pronounced after
      the dephytinization treatment. The addition of concentrated wheat bran and rice
      bran significantly increased hardness, as well as decreasing springiness,
      cohesiveness, and resilience of the bread, depending on the bran levels. Although
      dephytinization treatments enhanced the textural properties of bread, these
      results were still inferior to those obtained using bread produced with untreated
      bran. Regarding the dephytinization treatments, the influence of fermentation
      treatment on bread properties was slightly beneficial compared to hydrothermal
      treatment. PRACTICAL APPLICATIONS: Consumption of dietary fiber offers a range of
      health benefits. Cereal bran has great potential as a dietary fiber source.
      However, this bran's high phytic acid content and adverse effects on bread
      quality limit that potential. It is possible to obtain high dietary fiber and low
      phytic acid bran samples through bran concentration and dephytinization
      treatments. The dephytinization treatment is an effective method for degradation
      of phytic acid. The negative effects of wheat bran and rice bran on bread quality
      decreased significantly following the dephytinization treatments. This study
      demonstrated that fiber-enriched bread with low phytic acid content and
      acceptable texture can be produced using concentrated and dephytinized bran.

PMID- 28742222
TI  - Disruption of the ATP/adenosine balance in CD39-/- mice is associated with
      handling-induced seizures.
AB  - Seizures are due to excessive, synchronous neuronal firing in the brain and are
      characteristic of epilepsy, the fourth most prevalent neurological disease. We
      report handling-induced and spontaneous seizures in mice deficient for CD39, a
      cell-surface ATPase highly expressed on microglial cells. CD39-/- mice with
      handling-induced seizures had normal input-output curves and paired-pulse ratio
      measured from hippocampal slices and lacked microgliosis, astrogliosis or overt
      cell loss in the hippocampus and cortex. As expected, however, the cerebrospinal
      fluid of CD39-/- mice contained increased levels of ATP and decreased levels of
      adenosine. To determine if immune activation was involved in seizure progression,
      we challenged mice with lipopolysaccharide (LPS) and measured the effect on
      microglia activation and seizure severity. Systemic LPS challenge resulted in
      increased cortical staining of Iba1/CD68 and gene array data from purified
      microglia predicted increased expression of interleukin-8, triggering receptor
      expressed on myeloid cells 1, p38, pattern recognition receptors, death receptor,
      nuclear factor-kappaB , complement, acute phase, and interleukin-6 signalling
      pathways in CD39-/- versus CD39+/+ mice. However, LPS treatment did not affect
      handling-induced seizures. In addition, microglia-specific CD39 deletion in adult
      mice was not sufficient to cause seizures, suggesting instead that altered
      expression of CD39 during development or on non-microglial cells such as vascular
      endothelial cells may promote the seizure phenotype. In summary, we show a
      correlation between altered extracellular ATP/adenosine ratio and a previously
      unreported seizure phenotype in CD39-/- mice. This work provides groundwork for
      further elucidation of the underlying mechanisms of epilepsy.

PMID- 28742223
TI  - Impact and implementation of a sustainable regional telestroke network.
AB  - BACKGROUND: Telestroke uses videoconferencing technology to allow off-site
      experts to provide stroke thrombolysis decision support to less experienced front
      line clinicians. AIM: To assess the impact of a new telestroke service on
      thrombolysis rates and door-to-needle times in participating provincial hospitals
      and service resources to aid transition to a sustainable telestroke service.
      METHODS: This is a sequential comparison of 'pre' (December 2015 to May 2016) and
      'post' (June 2016 to December 2016) implementation outcomes. The main outcomes
      were thrombolysis rate and door-to-needle time. All patient data were captured
      prospectively in a central database. Data captured and analysed also included
      technical problems, consumer and clinician feedback, and additional service
      resources required. RESULTS: Over the study period, 164 telestroke assessments
      were completed, including the 'hub' hospital. Among the participating provincial
      hospitals, 21 of 343 patients (6.1%) were thrombolysed in the 6-months prior to
      June 2016 and 50 of 318 patients (15.7%) during the 6-month following
      implementation of telestroke; odds ratio 2.86 (95% confidence interval 1.68
      4.89); P = 0.0001. Overall, mean (standard deviation) regional hospital door-to
      needle time reduced from 79.6 (31.4) to 62.7 (23.3) min (P = 0.015).
      Videoconferencing failure occurred in 4.8% of cases. Consumer and clinician
      feedback was positive. The main resource challenge was doubling of out-of-hours
      neurologist workload. CONCLUSION: Telestroke was associated with a significant
      increase in thrombolysis rate and reduction in door-to-needle time in provincial
      hospitals indicating improved patient care. Quantification of the extra
      neurologist workload allowed for a seamless transition to 'business as usual'
      using a novel annual subscription funding and service model.

PMID- 28742224
TI  - Synthesis of Unimolecular Micelles with Incorporated Hyperbranched Boltorn H30
      Polyester modified with Hyperbranched Helical Poly(phenyl isocyanide) Chains and
      their Enantioselective Crystallization Performance.
AB  - Here, the fabrication of unimolecular micelles functionalized with helical
      polymeric chains as a chiral nucleating agent in enantioselective crystallization
      is reported. Starting from a fractionated hyperbranched polyester (Boltorn H30),
      the ring-opening polymerization of l-lactic acid (LLA) and subsequent terminal
      group modification affords the alkyne-Pd(II)-anchored hyperbranched
      macroinitiator (H30-PLLA-Pd). By taking advantage of a Pd(II)-catalyzed living
      polymerization of chiral pendant modified l- or d-phenyl isocyanide (PI)
      monomers, well-defined chiral unimolecular micelles (H30-PLLA-PPI) grafted with
      radiating helical PPI coronas of one predominant screw sense are obtained. The
      resultant chiral materials demonstrate excellent application in the
      enantioselective crystallization of racemic threonine in water, and a 92%
      enantiomeric excess value of the residual solution is obtained. It is believed
      this present proof of concept and methodology are facile and powerful for
      preparing novel and versatile chiral materials with different topological
      structures, not only applicable to PPI but also to other types of polymers.

PMID- 28742225
TI  - Efficacy and safety of lixisenatide in a predominantly Asian population with type
      2 diabetes insufficiently controlled with basal insulin: The GetGoal-L-C
      randomized trial.
AB  - AIMS: To assess the effects on glycaemic control of lixisenatide vs placebo as
      add-on treatment to basal insulin (BI) +/- metformin and effects on glycated
      haemoglobin (HbA1c) reduction in patients with insufficiently controlled type 2
      diabetes (T2D). METHODS: Patients (n = 448) with inadequately controlled T2D were
      randomized (1:1) to lixisenatide or placebo as add-on to BI +/- metformin for 24
      weeks after an 8-week run-in phase, during which BI was titrated to a target self
      monitored plasma glucose (SMPG; 4.4-5.6 mmol/L). The primary endpoint was
      absolute change in HbA1c from baseline to week 24. Secondary efficacy endpoints
      included: percentage of responders; changes in 2-hour postprandial plasma glucose
      (PPG); 7-point SMPG (daily average); body weight (BW); total daily BI dose;
      fasting plasma glucose; and safety assessments. RESULTS: Baseline demographics
      were similar in the two treatment groups. After insulin optimization during run
      in, lixisenatide was superior to placebo in mean change from baseline (7.9%
      [standard deviation {s.d.}, 0.66] and 7.9% [0.70], respectively) to week 24 in
      HbA1c (least squares mean [standard error {s.e.}] change -0.62% [0.09] vs -0.11%
      [0.09]; P < .0001, respectively) and higher proportions of patients achieved
      HbA1c targets. Two-hour PPG, daily mean SMPG and mean BW were reduced further and
      daily BI dose was lower with lixisenatide than placebo (-1.12 kg vs 0.04 kg [P <
      .0001]; -3.0 U vs -1.9 U [P = .0033], respectively). Treatment-emergent adverse
      events were greater with lixisenatide than placebo (63.8% vs 40.8%,
      respectively). The incidence of symptomatic hypoglycaemia was similar
      (lixisenatide 15.6% vs placebo 13.5%). CONCLUSIONS: In Asian patients
      insufficiently controlled on BI +/- metformin, lixisenatide was superior to
      placebo in glycaemic control, with a tolerability profile in line with other
      glucagon-like peptide-1 receptor agonists. CLINICAL TRIAL NUMBER: NCT01632163
      (clinicaltrials.gov).

PMID- 28742226
TI  - Documentation of penicillin adverse drug reactions in electronic health records:
      inconsistent use of allergy and intolerance labels.
AB  - BACKGROUND: The majority of patients with penicillin allergy labels tolerate
      penicillins. Inappropriate avoidance of penicillin is associated with increased
      hospitalisation, infections and healthcare costs. AIMS: To examine the
      documentation of penicillin adverse drug reactions (ADR) in a large-scale
      hospital-based electronic health record. METHODS: Penicillin ADR were extracted
      from 96 708 patient records in the Enterprise Patient Administration System in
      South Australia. Expert criteria were used to determine consistency of ADR entry
      and suitability for further evaluation. RESULTS: Of 43 011 unique ADR reports,
      there were 5023 ADR to penicillins with most being entered as allergy (n = 4773,
      95.0%) rather than intolerance (n = 250, 5.0%). A significant proportion did not
      include a reaction description (n = 1052, 20.9%). Using pre-set criteria, 10.1%
      of reports entered as allergy had a reaction description that was consistent with
      intolerance and 31.0% of the entered intolerances had descriptions consistent
      with allergy. Virtually all ADR (n = 4979, 99.1%) were appropriate for further
      evaluation by history taking or immunological testing and half (50.7%, n = 2549)
      had documented reactions suggesting low-risk of penicillin allergy. CONCLUSION:
      The frequency of penicillin allergy label in this data set is consistent with the
      known overdiagnosis of penicillin allergy in the hospital population. ADR
      documentation was poor with incomplete entries and inconsistent categorisation.
      The concepts of allergy and intolerance for ADR classification, whilst
      mechanistically valid, may not be useful at the point of ADR entry by generalist
      clinicians. Systematic evaluation of reported ADR is needed to improve the
      quality of information for future prescribers.

PMID- 28742227
TI  - Melatonin prevents mitochondrial dysfunctions and death in differentiated
      skeletal muscle cells.
AB  - Oxidative stress increase induces cellular damage and apoptosis activation, a
      mechanism believed to represent a final common pathway correlated to sarcopenia
      and many skeletal muscle disorders. The goal of this study is to evaluate if
      melatonin, a ROS scavenger molecule, is able to counteract or modulate myotube
      death. Here, differentiated C2C12 skeletal muscle cells have been treated with
      melatonin before chemicals known to induce apoptotic death and oxidative stress,
      and its effect has been investigated by means of morpho-functional analyses.
      Ultrastructural observations show melatonin protection against triggers by the
      reducing of membrane blebbing, chromatin condensation, myonuclei loss and in situ
      DNA cleavage. Moreover, melatonin is able to prevent mitochondrial dysfunctions
      which occur in myotubes exposed to the trigger alone. These findings demonstrate
      melatonin ability in preventing apoptotic cell death in skeletal muscle fibers in
      vitro, suggesting for this molecule a potential therapeutic role in the treatment
      of various muscle disorders.

PMID- 28742228
TI  - Prevalence and predictors of conflict in the families of patients with advanced
      cancer: A nationwide survey of bereaved family members.
AB  - OBJECTIVES: Family conflict has several adverse impacts on caregivers. Thus,
      there is significant value in determining the prevalence and predictors of family
      conflict, which can enable the health care provider to intervene if family
      conflict arises during end-of-life care. Accordingly, we aimed to explore the
      prevalence and predictors of conflict among the families of patients with
      advanced cancer who died in palliative care units. METHODS: This study was a
      nationwide multicenter questionnaire survey of bereaved family members of cancer
      patients who died in Japanese palliative care units participating in evaluation
      of the quality of end-of-life care. RESULTS: We sent out 764 questionnaires, and
      529 questionnaires (69.2%) were returned. As 70 family members refused to
      participate and we could not identify the answers in one questionnaire, we
      analyzed a total of 458 responses. The average Outcome-Family Conflict score was
      13.5 +/- 4.9 (maximum score: 39.5), and 42.2% of family members reported at least
      one family conflict during end-of-life care. Greater family conflict was
      significantly associated with younger family age, with family members asserting
      control over decision making for patient care and with communication constraints
      among family members, although absent family members "coming out of the woodwork"
      reduced family conflict. CONCLUSIONS: Many families of patients with advanced
      cancer experienced conflict during end-of-life care. Family members asserting
      control over decision making and communication constraints among family members
      after diagnosis of cancer can predict the occurrence of family conflict. Absent
      family members "coming out of the woodwork" might reduce family conflict in
      particular cultures.

PMID- 28742229
TI  - Association between obesity with low muscle mass and dialysis mortality.
AB  - BACKGROUND/AIM: To examine the association between body composition and dialysis
      mortality. METHODS: Adult patients who underwent haemodialysis in Taoyuan General
      Hospital from 2012 to 2016 were enrolled. We reviewed their baseline
      characteristics and followed up their treatment over 5 years after dialysis.
      Patients with body mass index >25 kg/m2 were defined as obese. High or low muscle
      mass were classified by skeletal muscle mass index (SMMI) based on consensus from
      Chinese population. All age-matched subjects were classified into four groups:
      (A) optimal; (B) obesity; (C) low muscle mass; and (D) obesity with low muscle
      mass. Adjusted hazard ratios for mortality and cumulative survival curves were
      evaluated by Cox proportional hazard model and Kaplan-Meier method. The
      discriminative power of SMMI was calculated according to the area under the curve
      and the receiver operating characteristic curve. RESULTS: From a total of 176 age
      matched patients, the incidence rates of mortality for different groups were 3.7,
      7.8, 10.3 and 16.5 per 1000 person-months. After adjusting for continuous
      variables, SMMI was independently associated with mortality. The difference
      between groups A and D was more significant in women than in men after
      multivariate adjustment (adjusted hazard ratios: 7.465 vs 1.682) (P = 0.035 and
      0.553). The discriminative power of SMMI to predict 5-year mortality was 0.700
      for men and 0.750 for women, and the best cut-off values were 11.1 and 8.4 kg/m2
      CONCLUSIONS: Low muscle mass was associated with dialysis mortality. Obesity with
      low muscle mass was a predictor for dialysis mortality in women.

PMID- 28742230
TI  - Allopatric speciation despite historical gene flow: Divergence and hybridization
      in Carex furva and C. lucennoiberica (Cyperaceae) inferred from plastid and
      nuclear RAD-seq data.
AB  - Gene flow among incipient species can act as a creative or destructive force in
      the speciation process, generating variation on which natural selection can act
      while, potentially, undermining population divergence. The flowering plant genus
      Carex exhibits a rapid and relatively recent radiation with many species limits
      still unclear. This is the case with the Iberian Peninsula (Spain and Portugal)
      endemic C. lucennoiberica, which lay unrecognized within Carex furva until its
      recent description as a new species. In this study, we test how these species
      were impacted by interspecific gene flow during speciation. We sampled the full
      range of distribution of C. furva (15 individuals sampled) and C. lucennoiberica
      (88 individuals), sequenced two cpDNA regions (atpI-atpH, psbA-trnH) and
      performed genomic sequencing of 45,100 SNPs using restriction site-associated DNA
      sequencing (RAD-seq). We utilized a set of partitioned D-statistic tests and
      demographic analyses to study the degree and direction of introgression.
      Additionally, we modelled species distributions to reconstruct changes in range
      distribution during glacial and interglacial periods. Plastid, nuclear and
      morphological data strongly support divergence between species with subsequent
      gene flow. Combined with species distribution modelling, these data support a
      scenario of allopatry leading to species divergence, followed by secondary
      contact and gene flow due to long-distance dispersal and/or range expansions and
      contractions in response to Quaternary glacial cycles. We conclude that this is a
      case of allopatric speciation despite historical secondary contacts, which could
      have temporally influenced the speciation process, contributing to the knowledge
      of forces that are driving or counteracting speciation.

PMID- 28742232
TI  - Altering the Coordination of Iron Porphyrins by Ionic Liquid Nanodomains in Mixed
      Solvent Systems.
AB  - The solvent environment around iron porphyrin complexes was examined using mixed
      molecular/RTIL (room temperature ionic liquid) solutions. The formation of
      nanodomains in these solutions provides different solvation environments for
      substrates that could have significant impact on their chemical reactivity. Iron
      porphyrins (Fe(P)), whose properties are sensitive to solvent and ligation
      changes, were used to probe the molecular/RTIL environment. The addition of RTILs
      to molecular solvents shifted the redox potentials to more positive values. When
      there was no ligation change upon reduction, the shift in the E degrees  values
      were correlated to the Gutmann acceptor number, as was observed for other
      porphyrins with similar charge changes. As %RTIL approached 100 %, there was
      insufficient THF to maintain coordination and the E degrees  values were much
      more dependent upon the %RTIL. In the case of FeIII (P)(Cl), the shifts in the E
      degrees  values were driven by the release of the chloride ion and its strong
      attraction to the ionic liquid environment. The spectroscopic properties and
      distribution of the FeII and FeI species into the RTIL nanodomains were monitored
      with visible spectroelectrochemistry, 19 F NMR and EPR spectroscopy. This
      investigation shows that coordination and charge delocalization (metal versus
      ligand) in the metalloporphyrins redox products can be altered by the RTIL
      fraction in the solvent system, allowing an easy tuning of their chemical
      reactivity.

PMID- 28742231
TI  - Different resuscitation strategies and novel pharmacologic treatment with
      valproic acid in traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a leading cause of death in young adults, and
      effective treatment strategies have the potential to save many lives. TBI results
      in coagulopathy, endothelial dysfunction, inflammation, cell death, and impaired
      epigenetic homeostasis, ultimately leading to morbidity and/or mortality.
      Commonly used resuscitation fluids such as crystalloids or colloids have several
      disadvantages and might even be harmful when administered in large quantities.
      There is a need for next-generation treatment strategies (especially in the
      prehospital setting) that minimize cellular damage, improve survival, and enhance
      neurological recovery. Pharmacologic treatment with histone deacetylase
      inhibitors, such as valproic acid, has shown promising results in animal studies
      of TBI and may therefore be an excellent example of next-generation therapy. This
      review briefly describes traditional resuscitation strategies for TBI combined
      with hemorrhagic shock and describes preclinical studies on valproic acid as a
      new pharmacologic agent in the treatment of TBI. It finally discusses limitations
      and future directions on the use of histone deacetylase inhibitors for the
      treatment of TBI.

PMID- 28742233
TI  - Controlled Supramolecular Self-Assembly of Super-charged beta-Lactoglobulin A-PEG
      Conjugates into Nanocapsules.
AB  - The synthesis and characterization of a new protein-polymer conjugate composed of
      beta lactoglobulin A (betaLG A) and poly(ethylene glycol) PEG is described.
      betaLG A was selectively modified to self-assemble by super-charging via
      amination or succinylation followed by conjugation with PEG. An equimolar mixture
      of the oppositely charged protein-polymer conjugates self-assemble into spherical
      capsules of 80-100 nm in diameter. The self-assembly proceeds by taking
      simultaneous advantage of the amphiphilicity and polyelectrolyte nature of the
      protein-polymer conjugate. These protein-polymer capsules or proteinosomes are
      reminiscent of protein capsids, and are capable of encapsulating solutes in their
      interior. We envisage this approach to be applicable to other globular proteins.

PMID- 28742234
TI  - Xylella fastidiosa: an examination of a re-emerging plant pathogen.
AB  - : Xylella fastidiosa is a Gram-negative bacterial plant pathogen with an
      extremely wide host range. This species has recently been resolved into
      subspecies that correlate with host specificity. This review focuses on the
      status of X. fastidiosa pathogenic associations in plant hosts in which the
      bacterium is either endemic or has been recently introduced. Plant diseases
      associated with X. fastidiosa have been documented for over a century, and much
      about what is known in the context of host-pathogen interactions is based on
      these hosts, such as grape and citrus, in which this pathogen has been well
      described. Recent attention has focused on newly emerging X. fastidiosa diseases,
      such as in olives. TAXONOMY: Bacteria; Gammaproteobacteria; family
      Xanthomonadaceae; genus Xylella; species fastidiosa. MICROBIOLOGICAL PROPERTIES:
      Gram-negative rod (0.25-0.35 * 0.9-3.5 MUm), non-flagellate, motile via Type IV
      pili-mediated twitching, fastidious. HOST RANGE: Xylella fastidiosa has a broad
      host range that includes ornamental, ecological and agricultural plants belonging
      to over 300 different species in 63 different families. To date, X. fastidiosa
      has been found to be pathogenic in over 100 plant species. In addition, it can
      establish non-symptomatic associations with many plants as a commensal endophyte.
      Here, we list the four distinct subspecies of X. fastidiosa and some of the
      agriculturally relevant diseases caused by them: X. fastidiosa ssp. fastidiosa
      causes Pierce's disease (PD) of grapevine (Vitis vinifera); X. fastidiosa ssp.
      multiplex causes almond leaf scorch (ALS) and diseases on other nut and shade
      tree crops; X. fastidiosa ssp. pauca causes citrus variegated chlorosis (CVC)
      (Citrus spp.), coffee leaf scorch and olive quick decline syndrome (OQDS) (Olea
      europaea); X. fastidiosa ssp. sandyi causes oleander leaf scorch (OLS) (Nerium
      oleander). Significant host specificity seemingly exists for some of the
      subspecies, although this could be a result of technical biases based on the
      limited number of plants tested, whereas some subspecies are not as stringent in
      their host range and can infect several plant hosts. DISEASE SYMPTOMS: Most X.
      fastidiosa-related diseases appear as marginal leaf necrosis and scorching of the
      leaves. In the case of PD, X. fastidiosa can also cause desiccation of berries
      (termed 'raisining'), irregular periderm development and abnormal abscission of
      petioles. In olive trees affected with OQDS, leaves exhibit marginal necrosis and
      defoliation, and overall tree decline occurs. Plants with ALS and OLS also
      exhibit the characteristic leaf scorch symptoms. Not all X. fastidiosa-related
      diseases exhibit the typical leaf scorch symptoms. These include CVC and Phony
      Peach disease, amongst others. In the case of CVC, symptoms include foliar wilt
      and interveinal chlorosis on the upper surfaces of the leaves (similar to zinc
      deficiency), which correspond to necrotic, gum-like regions on the undersides of
      the leaves. Additional symptoms of CVC include defoliation, dieback and hardening
      of fruits. Plants infected with Phony Peach disease exhibit a denser, more
      compact canopy (as a result of shortened internodes, darker green leaves and
      delayed leaf senescence), premature bloom and reduced fruit size. Some occlusions
      occur in the xylem vessels, but there are no foliar wilting, chlorosis or
      necrosis symptoms . USEFUL WEBSITES: http://www.piercesdisease.org/;
      https://pubmlst.org/xfastidiosa/; http://www.xylella.lncc.br/;
      https://nature.berkeley.edu/xylella/;
      https://ec.europa.eu/food/plant/plant_health_biosecurity/legislation/emergency_me
      sures/xylella-fastidiosa_en.

PMID- 28742235
TI  - Silver delivery approaches in the management of partial thickness burns: A
      systematic review and indirect treatment comparison.
AB  - Silver-containing products play an important role in the management of burn wound
      infections. We sought to compare the efficacy of commonly used silver delivery
      approaches including nanocrystalline silver, silver-impregnated hydrofiber
      dressing, and silver-impregnated foam dressing as the main products in the
      management of partial thickness burns. A systematic review was performed by
      searching PubMed, EMBASE, Cochrane, and other databases to identify relevant
      randomized controlled trials and observational studies. Due to the paucity of
      direct head-to-head trials, an indirect treatment comparison was performed. The
      use of nanocrystalline silver was associated with a statistically significant
      reduction in length of stay when compared to silver-impregnated hydrofiber
      dressing (p = 0.027) and a shorter time to healing when compared to silver
      impregnated foam dressing (p = 0.0328). There were no statistically significant
      differences in infection rates and surgical procedures between nanocrystalline
      silver, silver-impregnated hydrofiber dressing, and silver-impregnated foam
      dressing; however, nanocrystalline silver was found to be the most beneficial for
      all the outcomes, including infection rates and surgical procedures, according to
      the Monte Carlo simulation method. In conclusion, current evidence from the
      published literature suggests that where the clinical and microbiological
      priority is to get in control of infection quickly it would seem prudent to use
      the most potent silver delivery system, which is nanocrystalline silver.
      Nanocrystalline silver may offer both clinical and economic benefits compared to
      alternative treatments in the management of patients with mixed burns that are at
      high risk of infection.

PMID- 28742236
TI  - XYLEM NAC DOMAIN1, an angiosperm NAC transcription factor, inhibits xylem
      differentiation through conserved motifs that interact with RETINOBLASTOMA
      RELATED.
AB  - The Arabidopsis thaliana gene XYLEM NAC DOMAIN1 (XND1) is upregulated in xylem
      tracheary elements. Yet overexpression of XND1 blocks differentiation of
      tracheary elements. The molecular mechanism of XND1 action was investigated.
      Phylogenetic and motif analyses indicated that XND1 and its homologs are present
      only in angiosperms and possess a highly conserved C-terminal region containing
      linear motifs (CKII-acidic, LXCXE, E2FTD -like and LXCXE-mimic) predicted to
      interact with the cell cycle and differentiation regulator RETINOBLASTOMA-RELATED
      (RBR). Protein-protein interaction and functional analyses of XND1 deletion
      mutants were used to test the importance of RBR-interaction motifs. Deletion of
      either the LXCXE or the LXCXE-mimic motif reduced both the XND1-RBR interaction
      and XND1 efficacy as a repressor of differentiation, with loss of the LXCXE motif
      having the strongest negative impacts. The function of the XND1 C-terminal domain
      could be partially replaced by RBR fused to the N-terminal domain of XND1. XND1
      also transactivated gene expression in yeast and plants. The properties of XND1,
      a transactivator that depends on multiple linear RBR-interaction motifs to
      inhibit differentiation, have not previously been described for a plant protein.
      XND1 harbors an apparently angiosperm-specific combination of interaction motifs
      potentially linking the general differentiation regulator RBR with a xylem
      specific pathway for inhibition of differentiation.

PMID- 28742237
TI  - Asymmetric Synthesis of alpha,alpha-Disubstituted Allylic Amines through
      Palladium-Catalyzed Allylic Substitution.
AB  - The first asymmetric synthesis of important alpha,alpha-disubstituted N-alkyl
      allyl amine scaffolds through allylic substitution is reported. This approach is
      based on palladium catalysis and features ample scope with respect to both the
      allylic precursor and amine reagent, and high asymmetric induction with
      enantiomeric ratios (e.r.) up to 98.5:1.5. The use of less-reactive anilines is
      also feasible, providing enantioenriched alpha,alpha-disubstituted N-aryl allylic
      amines.

PMID- 28742238
TI  - HLA-A*24:02:01:09, a new allele identified by sequence-based typing in a Korean
      individual.
AB  - One nucleotide insertion between residues 1804 and 1805 of HLA-A*24:02:01:01
      results in a new allele, HLA-A*24:02:01:09.

PMID- 28742239
TI  - A scoping review of skills and tools oral health professionals need to engage
      children and parents in dietary changes to prevent childhood obesity and
      consumption of sugar-sweetened beverages.
AB  - OBJECTIVES: Increased consumption of sugar-sweetened beverages (SSBs) has been
      linked to obesity. Obesity now affects one in six children in the United States.
      The purpose of this scoping review is to identify and review published studies
      that discuss skills and tools oral health professionals can use with children
      (under age 12) and their parents to encourage dietary changes to aid in
      preventing childhood obesity and reducing consumption of SSBs. METHODS: Key
      search terms were identified and used to examine selected databases via PubMed,
      EMBASE, CINAHL, and Cochrane Database of Systematic Reviews. A total of 637
      records were identified. After duplicates were removed and records were screened
      for eligibility, 33 remained. Six met established inclusion/exclusion criteria
      and were included in the review. RESULTS: Only two full-text articles included
      dental-office-based weight interventions. Patient response to education on
      healthy habits and weight maintenance in the dental setting was favorable.
      Literature supports oral health professionals expanding their role in health care
      delivery by offering nutrition and physical activity recommendations to prevent
      and/or reduce chronic disease. Active listening and motivational interviewing
      were techniques identified to promote beneficial lifestyle changes. CONCLUSIONS:
      There is limited research on behavior modification tools and skills that have
      been effectively implemented in the dental setting to decrease risk of obesity.
      Oral health professionals are uniquely positioned to address consumption of SSBs
      and promote positive dietary habits for improved weight management. Future
      studies are needed to identify effective techniques that techniques that oral
      health professionals can integrate into preventive patient care.

PMID- 28742241
TI  - Cervical Epidural Injection in the Management of Refractory Pain and Stiffness in
      Spondyloarthropathy: A Case Report Series.
AB  - OBJECTIVES: The primary objective of this case series was to report the use of
      cervical epidural steroid injection in the management of neck pain and stiffness
      secondary to spondyloarthropathy in cases refractory to conservative therapy.
      METHODS: This was a case report series on three patients with diagnosis of
      spondyloarthropathy who presented with severe stiffness and non-radicular axial
      neck pain refractory to conservative therapy. All patients received cervical
      epidural steroid injections with significant improvement of their axial neck pain
      and stiffness. RESULTS: Cervical epidural steroid injections may be effective to
      improve the axial neck pain and stiffness in patients with diagnosis of
      spondyloarthropathy refractory to conservative management. Thus, we believe that
      epidural steroid injections should be considered in the management of patients
      with spondyloarthopathies.

PMID- 28742240
TI  - Role of tissue eosinophils in chronic rhinosinusitis-associated olfactory loss.
AB  - BACKGROUND: Olfactory dysfunction is 1 of the hallmark symptoms of chronic
      rhinosinusitis (CRS). Eosinophilic inflammation has been implicated as a
      potential causative factor. However, prior studies have been limited by
      retrospective study designs, concomitant use of systemic corticosteroids, and
      other confounding factors. METHODS: CRS and healthy non-CRS control subjects
      undergoing endoscopic sinus or skull-base surgery were prospectively enrolled and
      completed olfactory testing utilizing the 40-item Smell Identification Test (SIT)
      immediately prior to surgery. Histopathological evaluation of tissue excised from
      the ethmoid bulla was performed by a pathologist in a blinded fashion. Disease
      severity and patient-reported outcomes were measured via the Lund-Mackay computed
      tomography (CT) grading system and 22-item Sino-Nasal Outcome Test (SNOT-22),
      respectively. The associations between olfactory function, tissue eosinophilia,
      and disease severity were analyzed using Spearman rank order correlation and
      multiple linear regression. RESULTS: Twenty-seven (27) subjects with CRS without
      nasal polyps (CRSsNP), 32 subjects with CRS with nasal polyps (CRSwNP), and 10
      healthy non-CRS controls were enrolled. CRSwNP was associated with higher mean
      tissue eosinophil counts (71.6 vs 28.1 eosinophils/high-power field [HPF], p <
      0.05) and lower age/sex-adjusted SIT scores (-17.4 vs -6.2, p < 0.001) when
      compared to CRSsNP. SIT scores were strongly negatively correlated with tissue
      eosinophil counts in CRSwNP (r = -0.60, p = 0.0003), but not CRSsNP (r = 0.16, p
      = 0.42). The correlation between olfactory function and tissue eosinophilia in
      CRSwNP persisted after adjusting for disease severity. CONCLUSION: Tissue
      eosinophilia is associated with olfactory loss in CRSwNP, independent of disease
      severity. These results suggest a possible role for eosinophils or eosinophil
      associated cytokines in CRS-associated olfactory loss.

PMID- 28742242
TI  - Multidisciplinary Team Treatment Approaches to Chronic Daily Headaches.
AB  - OBJECTIVE: In this review, we focus on nonmedication treatment approaches to
      chronic daily headaches and chronic migraine. We review the current scientific
      data on studies using multimodal treatments, especially physical therapy and
      occupational therapy, and provide recommendations on the formation of
      interdisciplinary headache teams. BACKGROUND: Chronic daily headache, which
      includes chronic migraine, is a particularly challenging clinical entity which
      often involves multiple headache types and comorbidities. A team approach in
      treating these patients may be particularly useful. DESIGN/METHODS: We review all
      current studies performed with at least one or more other modality in addition to
      usual medical treatment, with a focus on physical and occupational therapy.
      Emphasis on physical and occupational therapy with an explanation of their
      methods and role in multidisciplinary treatment is a pivotal part of this review.
      We also suggest approaches to setting up a multimodality clinic for the busy
      headache clinician. CONCLUSION: Setting up a collaborative, multidisciplinary
      team of specialists in headache practices with the goal of modifying physical,
      environmental, and psychological triggers for chronic daily headaches may
      facilitate treatment of these refractory patients.

PMID- 28742243
TI  - Data privacy management and data quality monitoring in the German Centre for
      Cardiovascular Research's multicentre TranslatiOnal Registry for CardiomyopatHies
      (DZHK-TORCH).
AB  - AIMS: The multicentric TranslatiOnal Registry for CardiomyopatHies (TORCH) of the
      German Centre for Cardiovascular Research aims to recruit 2300 patients with non
      ischemic cardiomyopthies. METHODS AND RESULTS: The investigations were performed
      after standard operating procedures. The data are collected in standardized
      electronic case report forms provided by the data holding of the central data
      management of the German Centre for Cardiovascular Research using secuTrial
      (interActive Systems GmbH, Berlin, Germany). The personal-identifying data and
      informed consent are collected, stored, and quality-checked by the independent
      Trusted Third Party in Greifswald. The quality management of the medical data is
      performed by the data and quality centre Greifswald. In December 2014, the
      recruitment for TORCH has started. Currently, data and biomaterial from about
      1397 patients and more than 74 500 biomaterial aliquots were collected. Regular
      study centre-specific quality reports address completeness and plausibility of
      data and provide detailed information about current missing or implausible data
      entries to improve the data quality by using a query management in addition.
      CONCLUSIONS: A regular quality control and reporting improve the data quality in
      TORCH and will support high-quality data analysis and the translation of research
      results into routine care.

PMID- 28742244
TI  - Novel PRPS1 gain-of-function mutation in a patient with congenital hyperuricemia
      and facial anomalies.
AB  - Phosphoribosylpyrophosphate synthetase (PRPPS) superactivity (OMIM 300661) is a
      rare inborn error of purine metabolism that is caused by gain-of-function
      mutations in the X-chromosomal gene PRPS1 (Xq22.3). Clinical characteristics
      include congenital hyperuricemia and hyperuricosuria, gouty arthritis,
      urolithiasis, developmental delay, hypotonia, recurrent infections, short
      stature, and hearing loss. Only eight families with PRPPS superactivity and PRPS1
      gain-of-function mutations have been reported to date. We report on a 7-year-old
      boy with congenital hyperuricemia, urolithiasis, developmental delay, short
      stature, hypospadias, and facial dysmorphisms. His mother also suffered from
      hyperuricemia that was diagnosed at age 13 years. A novel PRPS1 missense mutation
      (c.573G>C, p.[Leu191Phe]) was detected in the proband and his mother. Enzyme
      activity analysis confirmed superactivity of PRPP synthetase. Analysis of the
      crystal structure of human PRPPS suggests that the Leu191Phe mutation affects the
      architecture of both allosteric sites, thereby preventing the allosteric
      inhibition of the enzyme. The family reported here broadens the clinical spectrum
      of PRPPS superactivity and indicates that this rare metabolic disorder might be
      associated with a recognizable facial gestalt.

PMID- 28742245
TI  - Patients' Expectations on Spinal Cord Stimulation for Failed Back Surgery
      Syndrome: A Qualitative Exploration.
AB  - BACKGROUND: Spinal cord stimulation (SCS) is an effective therapy to reduce pain
      in patients who suffer from failed back surgery syndrome (FBSS). In order to
      inform patients optimally prior to this therapy, knowing their expectations is
      crucial. METHODS: Thirteen patients suffering from FBSS and scheduled for SCS
      were interviewed using a semistructured protocol. Patients were interviewed
      either at home or at their treating hospital. Data from these interviews were
      analyzed using directed content analysis. In addition to the qualitative
      interviews, an adjusted Brief Pain Inventory questionnaire was used to quantify
      expectations. RESULTS: The expectations of patients with regard to SCS could be
      subdivided into 13 categories, which could be grouped into 6 general themes: (1)
      physical well-being, (2) social well-being, (3) material well-being, (4)
      emotional well-being, (5) development and activity, and (6) constraints of the
      procedure of SCS. These findings confirm patients' expectations about the
      improvement of their quality of life by SCS for FBSS. This indicates that
      assessing pain relief is not enough to adequately evaluate the effects of SCS.
      The small diversity within the studied population and the lack of patient-to
      patient education are 2 possible limitations of this study. CONCLUSIONS: To
      improve education for patients prior to SCS surgery and to evaluate the effects
      of SCS, a multidimensional approach needs to be implemented. Possible
      disadvantages of SCS need to be discussed prior to the treatment.

PMID- 28742246
TI  - Aquivion Perfluorosulfonic Superacid as an Efficient Pickering Interfacial
      Catalyst for the Hydrolysis of Triglycerides.
AB  - Rational design of the surface properties of heterogeneous catalysts can boost
      the interfacial activity in biphasic reactions through the generation of
      Pickering emulsions. This concept, termed Pickering interfacial catalysis (PIC),
      has shown promising credentials in acid-catalyzed transesterification, ester
      hydrolysis, acetalization, etherification, and alkylation reactions. PIC has now
      been applied to the efficient, solvent-free hydrolysis of the triglyceride
      glyceryl trilaurate to lauric acid, catalyzed by Aquivion perfluorosulfonic
      superacid at mild conditions (100  degrees C and ambient pressure).

PMID- 28742247
TI  - Ventana immunohistochemistry assay for anaplastic lymphoma kinase gene
      rearrangement detection in patients with non-small cell lung cancer: A meta
      analysis.
AB  - BACKGROUND: The aim of this study was to evaluate the diagnostic value of Ventana
      immunohistochemistry (IHC) assay for anaplastic lymphoma kinase (ALK) gene
      rearrangement screening in patients with non-small cell lung cancer (NSCLC).
      METHODS: Open published studies that reported the diagnostic performance of
      Ventana IHC assay for ALK gene rearrangement detection in NSCLC patients were
      extracted from PubMed, Embase, Google scholar, Wanfang, and China National
      Knowledge Infrastructure. The general information and number of true positive
      (tp), false positive (fp), false negative (fn), and true negative (tn) cases
      identified by Ventana IHC assay were extracted. The diagnostic sensitivity,
      specificity, positive likelihood ratio (+lr), negative likelihood ratio (-lr),
      diagnostic odds ratio (dor) and the summary receiver operating characteristic
      (ROC) curve were calculated using Stata 11.0 software. RESULTS: Ten studies,
      including 240 ALK positive and 1973 ALK negative NSCLC patients were included in
      this meta-analysis. The pooled diagnostic sensitivity, specificity, +lr, -lr, and
      dor were 0.94 (95% confidence interval [CI] 0.85-0.98), 1.00 (95% CI 0.99-1.00),
      859.61 (95% CI 60.81-1200.00), 0.06 (95% CI 0.03-0.16), and 1400.00 (95% CI
      813.29-23 000.00), respectively. The area under the ROC curve was 0.996 for
      Ventana IHC assay in detecting ALK gene rearrangement in NSCLC patients.
      CONCLUSION: The sensitivity and specificity of Ventana IHC assay for the
      detection of ALK gene rearrangement were high, thus Ventana IHC could substitute
      fluorescence in situ hybridization for the screening of ALK+ NSCLC patients.

PMID- 28742248
TI  - Biallelic COL3A1 mutations result in a clinical spectrum of specific structural
      brain anomalies and connective tissue abnormalities.
AB  - Vascular Ehlers-Danlos syndrome (type IV) is an autosomal dominant disorder
      caused by heterozygous variants of COL3A1. We identified biallelic COL3A1
      variants in two unrelated families. In a 3-year-old female with developmental
      delay the nonsense variant c.1282C>T, p.(Arg428*) was detected in combination the
      c.2057delC, p.(Pro686Leufs*105) frame shift variant. Both compound heterozygous
      variants were novel. This patient was born with bilateral clubfoot, joint laxity,
      and dysmorphic facial features. At the age of 2 years she developed an aneurysmal
      brain hemorrhage. Cerebral MRI showed a peculiar pattern of profound cerebral
      abnormalities including bilateral frontoparietal polymicrogyria of the
      cobblestone variant. In the second family, the two affected siblings were
      homozygous for the missense variant c.145C<G, p.(Pro49Ala) of COL3A1 and showed
      cobblestone-like cortical malformation, cerebellar cysts, and white matter
      abnormalities, developmental delay, and seizures. To date, three further families
      have been reported with biallelic variants of this gene and specific structural
      brain anomalies in all, and a severe Ehlers-Danlos syndrome phenotype in some.
      Bilateral frontoparietal polymicrogyria of the cobblestone variant, cerebellar
      microcysts, and abnormalities of the white matter characterize this brain
      phenotype and resemble neurological manifestations in individuals with autosomal
      recessive mutations in GPR56, which serves as a ligand of COL3A1. In concordance
      with the findings in knock out mice, the collagen III protein plays a role in the
      regulation of cortical development in addition to its well-known function in
      connective tissue formation.

PMID- 28742249
TI  - Transient electroosmosis of a Maxwell fluid in a rotating microchannel.
AB  - The transient electroosmotic flow of Maxwell fluid in a rotating microchannel is
      investigated both analytically and numerically. We bring out the complex dynamics
      of the flow during the transience due to the combination of rotation and
      rheological effects. We show the regimes of operation under which our analysis
      holds the most significance. We also shed some light on the volumetric flow rate
      characteristics as dictated by the underlying flow physics. Mainly we show and
      analyze the various regimes of operation under which viscoelastic effects
      actuated by electroosmotic forcing dominate over Coriolis forces and vice versa,
      which has not been studied before. We also observe that the analytical solution
      compares well with the numerical solution. We believe that the results from the
      present study could potentially have far reaching applications in bio-fluidic
      microsystems where fluids such as blood, mucus and saliva may be involved.

PMID- 28742250
TI  - Copper-Catalyzed Decarboxylative Radical Silylation of Redox-Active Aliphatic
      Carboxylic Acid Derivatives.
AB  - A decarboxylative silylation of aliphatic N-hydroxyphthalimide (NHPI) esters
      using Si-B reagents as silicon pronucleophiles is reported. This C(sp3 )-Si cross
      coupling is catalyzed by copper(I) and follows a radical mechanism, even with
      exclusion of light. Both primary and secondary alkyl groups couple effectively,
      whereas tertiary alkyl groups are probably too sterically hindered. The
      functional-group tolerance is generally excellent, and alpha-heteroatom
      substituted substrates also participate well. This enables, for example, the
      synthesis of alpha-silylated amines starting from NHPI esters derived from alpha
      amino acids. The new method extends the still limited number of C(sp3 )-Si cross
      couplings of unactivated alkyl electrophiles.

PMID- 28742251
TI  - Evolution of Volatile Emission in Rhus coriaria Organs During Different Stages of
      Growth and Evaluation of the Essential Oil Composition.
AB  - Rhus coriaria, also known as Sumac, has been traditionally used in many countries
      as spice, condiment, dying agent, and medicinal herb. The chemical composition of
      essential oils (EOs) and the volatile emissions from different organs of this
      species collected in Sicily (Italy) were analyzed by gas chromatography-flame
      ionization detection and gas chromatography/mass spectrometry. Monoterpene and
      sesquiterpene hydrocarbons were the most abundant class in the volatile emissions
      with beta-caryophyllene and alpha-pinene were the main constituents in the
      majority of the examined samples. The EO composition was characterized by high
      amount of monoterpene and sesquiterpene hydrocarbons together with diterpenes.
      The main compounds in the EO obtained from the leaves and both stages of fruit
      maturation were cembrene and beta-caryophyllene, while alpha-pinene and
      tridecanoic acid were the key compounds in the flower EO. All the data were
      submitted to multivariate statistical analysis showing many differences among the
      different plant parts and their ontogenetic stages.

PMID- 28742252
TI  - Augmented and doubly robust G-estimation of causal effects under a Structural
      nested failure time model.
AB  - Structural nested failure time models (SNFTMs) are models for the effect of a
      time-dependent exposure on a survival outcome. They have been introduced along
      with so-called G-estimation methods to provide valid adjustment for time
      dependent confounding induced by time-varying variables. Adjustment for
      informative censoring in SNFTMs is possible via inverse probability of censoring
      weighting (IPCW). In the presence of considerable dropout, this can imply
      substantial information loss and consequently imprecise effect estimates. In this
      article, we aim to increase the efficiency of IPCW G-estimators under a SNFTM by
      deriving an augmented estimator that uses both censored and uncensored
      observations, and offers robustness against misspecification of the model for the
      censoring process, provided that a model for a specific functional of the
      survival time and time-dependent covariates is correctly specified. The empirical
      properties of the proposed estimators are studied in a simulation experiment, and
      the estimators are used in the analysis of surveillance data from the field of
      hospital epidemiology.

PMID- 28742253
TI  - Precisely Designed Isopeptide Bridge-Crosslinking Endows Artificial Hydrolases
      with High Stability and Catalytic Activity under Extreme Denaturing Conditions.
AB  - Enzymes normally lose their activities under extreme conditions due to the
      dissociation of their active tertiary structure. If an enzyme could maintain its
      catalytic activity under non-physiological or denaturing conditions, it might be
      used in more applications in the pharmaceutical and chemical industries.
      Recently, we reported a coiled-coil six-helical bundle (6HB) structure as a
      scaffold for designing artificial hydrolytic enzymes. Here, intermolecular
      isopeptide bonds were incorporated to enhance the stability and activity of such
      biomolecules under denaturing conditions. These isopeptide bridge-tethered 6HB
      enzymes showed exceptional stability against unfolding and retained or even had
      increased catalytic activity for a model hydrolysis reaction under thermal and
      chemical denaturing conditions. Thus, isopeptide bond-tethering represents an
      efficient route to construct ultrastable artificial hydrolases, with promising
      potential to maintain biocatalysis under extreme conditions.

PMID- 28742254
TI  - B-chrom: a database on B-chromosomes of plants, animals and fungi.

PMID- 28742255
TI  - Weight management strategies for those with chronic kidney disease: A consensus
      report from the Asia Pacific Society of Nephrology and Australia and New Zealand
      Society of Nephrology 2016 renal dietitians meeting.
AB  - AIM: The aim of the present study was to develop a consensus report to guide
      dietetic management of overweight or obese individuals with chronic kidney
      disease (CKD). METHODS: Six statements relating to weight management in CKD
      guided a comprehensive review of the literature. A summary of the evidence was
      then presented at the renal nutrition meeting of the 2016 Asia Pacific Society of
      Nephrology and Australia and New Zealand Society of Nephrology. Majority
      agreement was defined as group agreement on a statement of between 50-74%, and
      consensus was considered >=75% agreement. The recommendations were developed via
      a mini Delphi process. RESULTS: Two statements achieved group consensus: the
      current guidelines used by dietitians to estimate energy requirements for
      overweight and obese people with CKD are not relevant and weight loss medications
      may be unsafe or ineffective in isolation for those with CKD. One statement
      achieved group agreement: Meal replacement formulas are safe and efficacious in
      those with CKD. No agreement was achieved on the statements of whether there is
      strong evidence of benefit for weight loss prior to kidney transplantation;
      whether traditional weight loss strategies can be used in those with CKD and if
      bariatric surgery in those with end stage kidney disease is feasible and
      effective. CONCLUSION: There is a limited evidence base to guide the dietetic
      management of overweight and obese individuals with CKD. Medical or surgical
      strategies to facilitate weight loss are not recommended in isolation and require
      a multidisciplinary approach with the involvement of a skilled renal dietitian.

PMID- 28742256
TI  - Effect of Chenopodium ambrosioides on the healing process of the in vivo bone
      tissue.
AB  - The focus of this double-blind randomized study was on evaluating the effect of
      an aqueous extract of Mastruz (Chenopodium ambrosioides L.) on the bone repair
      process in vivo. In total, 36 male Wistar rats were randomly selected for this
      study, and divided into 3 groups (n = 12): Group HS (Hemostatic Sponge), Group SM
      (Hemostatic Sponge with Mastruz) and Group BC (Blood Clot). In each animal, bone
      defects measuring 2 mm in diameter were performed in both tibias for placement of
      the substances. After 3 and 10 days, the animals were sacrificed, and the tissues
      were analyzed under an optical microscope relative to the following events:
      inflammatory infiltrate; necrosis; young fibroblasts; osteoclastic and
      osteoblastic activity; endosteal and periosteal bone formation; and bone repair.
      The results were assessed by using Kruskal-Wallis and Mann-Whitney tests (p <
      .05). Inflammatory infiltrate demonstrated difference between Groups SM and BC in
      the time interval of 3 days (p = .004); an event related to the presence of the
      fibrin sponge and liquid of the extract, which induced a foreign body initial
      reaction. The presence of young fibroblasts (p = .003), osteoclastic (p = .003),
      and osteoblastic (p = .020) activity was statistically significant between Groups
      HS and BC in the time interval of 10 days; performance was related to the
      presence of the sponge within bone. As regards injured bone tissue repair, Group
      SM demonstrated a higher level of regenerative capacity (p = 0.004), due to a
      larger quantities of endosteal and periosteal bone formation, demonstrated in
      Group SM. The aqueous extract of mastruz stimulated bone neoformation, presenting
      wound closure with bone tissue at the end of 10 days.

PMID- 28742257
TI  - Dynamic Carboniferous tropical forests: new views of plant function and potential
      for physiological forcing of climate.
AB  - Contents 1333 I. 1334 II. 1335 III. 1339 IV. 1344 V. 1347 VI. 1347 1348 1348
      References 1348 SUMMARY: The Carboniferous, the time of Earth's penultimate
      icehouse and widespread coal formation, was dominated by extinct lineages of
      early-diverging vascular plants. Studies of nearest living relatives of key
      Carboniferous plants suggest that their physiologies and growth forms differed
      substantially from most types of modern vegetation, particularly forests. It
      remains a matter of debate precisely how differently and to what degree these
      long-extinct plants influenced the environment. Integrating biophysical analysis
      of stomatal and vascular conductivity with geochemical analysis of fossilized
      tissues and process-based ecosystem-scale modeling yields a dynamic and unique
      perspective on these paleoforests. This integrated approach indicates that key
      Carboniferous plants were capable of growth and transpiration rates that approach
      values found in extant crown-group angiosperms, differing greatly from
      comparatively modest rates found in their closest living relatives. Ecosystem
      modeling suggests that divergent stomatal conductance, leaf sizes and stem life
      span between dominant clades would have shifted the balance of soil-atmosphere
      water fluxes, and thus surface runoff flux, during repeated, climate-driven,
      vegetation turnovers. This synthesis highlights the importance of 'whole plant'
      physiological reconstruction of extinct plants and the potential of vascular
      plants to have influenced the Earth system hundreds of millions of years ago
      through vegetation-climate feedbacks.

PMID- 28742258
TI  - Metabolite profiling of non-sterile rhizosphere soil.
AB  - Rhizosphere chemistry is the sum of root exudation chemicals, their breakdown
      products and the microbial products of soil-derived chemicals. To date, most
      studies about root exudation chemistry are based on sterile cultivation systems,
      which limits the discovery of microbial breakdown products that act as
      semiochemicals and shape microbial rhizosphere communities. Here, we present a
      method for untargeted metabolic profiling of non-sterile rhizosphere soil. We
      have developed an experimental growth system that enables the collection and
      analysis of rhizosphere chemicals from different plant species. High-throughput
      sequencing of 16SrRNA genes demonstrated that plants in the growth system support
      a microbial rhizosphere effect. To collect a range of (a)polar chemicals from the
      system, we developed extraction methods that do not cause detectable damage to
      root cells or soil-inhabiting microbes, thus preventing contamination with
      cellular metabolites. Untargeted metabolite profiling by UPLC-Q-TOF mass
      spectrometry, followed by uni- and multivariate statistical analyses, identified
      a wide range of secondary metabolites that are enriched in plant-containing soil,
      compared with control soil without roots. We show that the method is suitable for
      profiling the rhizosphere chemistry of Zea mays (maize) in agricultural soil,
      thereby demonstrating the applicability to different plant-soil combinations. Our
      study provides a robust method for the comprehensive metabolite profiling of non
      sterile rhizosphere soil, which represents a technical advance towards the
      establishment of causal relationships between the chemistry and microbial
      composition of the rhizosphere.

PMID- 28742259
TI  - Off-label use of rituximab in autoimmune disease in the Top End of the Northern
      Territory, 2008-2016.
AB  - BACKGROUND: Rituximab, an anti-CD20 B-cell depleting monoclonal antibody, is
      increasingly prescribed off-label for a range of autoimmune diseases. There has
      not previously been an audit of off-label rituximab use in the Northern
      Territory, where the majority of patients are Aboriginal. AIMS: To evaluate
      retrospectively off-label rituximab use in autoimmune diseases in the Top End of
      the Northern Territory. METHODS: We performed a retrospective audit of 8 years of
      off-label rituximab use at the Royal Darwin Hospital, the sole tertiary referral
      centre for the Darwin, Katherine and East Arnhem regions. Electronic and paper
      records were reviewed for demographic information, diagnosis/indication for
      rituximab, doses, previous/concomitant immunosuppression, clinical outcomes and
      specific adverse events. RESULTS: Rituximab was prescribed off-label to 66
      patients for 24 autoimmune diseases. The majority of patients (62.1%) were
      Aboriginal and 60.6% female. The most common indications were
      refractory/relapsing disease despite standard therapies (68.7%) or severe disease
      with rituximab incorporated into an induction immunosuppressive regimen (19.4%).
      Systemic lupus erythematosus was the underlying diagnosis in 28.8% of cases. A
      clinically significant response was demonstrated in 74.2% of cases overall. There
      were 18 clinically significant infections; however, 13 were in patients receiving
      concurrent immunosuppressive therapy. There was a total of nine deaths from any
      cause. CONCLUSION: Rituximab has been used off-label for a range of autoimmune
      diseases in this population with a high proportion of Aboriginal patients
      successfully and safely in the majority of cases.

PMID- 28742260
TI  - Incorporating Patient Preferences into Estimation of Optimal Individualized
      Treatment Rules.
AB  - Precision medicine seeks to provide treatment only if, when, to whom, and at the
      dose it is needed. Thus, precision medicine is a vehicle by which healthcare can
      be made both more effective and efficient. Individualized treatment rules
      operationalize precision medicine as a map from current patient information to a
      recommended treatment. An optimal individualized treatment rule is defined as
      maximizing the mean of a pre-specified scalar outcome. However, in settings with
      multiple outcomes, choosing a scalar composite outcome by which to define
      optimality is difficult. Furthermore, when there is heterogeneity across patient
      preferences for these outcomes, it may not be possible to construct a single
      composite outcome that leads to high-quality treatment recommendations for all
      patients. We simultaneously estimate the optimal individualized treatment rule
      for all composite outcomes representable as a convex combination of the (suitably
      transformed) outcomes. For each patient, we use a preference elicitation
      questionnaire and item response theory to derive the posterior distribution over
      preferences for these composite outcomes and subsequently derive an estimator of
      an optimal individualized treatment rule tailored to patient preferences. We
      prove that as the number of subjects and items on the questionnaire diverge, our
      estimator is consistent for an oracle optimal individualized treatment rule
      wherein each patient's preference is known a priori. We illustrate the proposed
      method using data from a clinical trial on antipsychotic medications for
      schizophrenia.

PMID- 28742261
TI  - The clinical characteristics and audiogram in 103 Meniere's disease patients with
      and without vestibular migraine.

PMID- 28742262
TI  - Bladder neck needle suspension for urinary incontinence in women.
AB  - BACKGROUND: Bladder neck needle suspension is an operation traditionally used for
      moderate or severe stress urinary incontinence in women. About a third of adult
      women experience some urinary incontinence, and about a third of these have
      moderate or severe symptoms. Stress urinary incontinence (SUI) imposes
      significant health and economic burdens on society and the women affected.
      OBJECTIVES: To determine the effects of needle suspension on stress or mixed
      urinary incontinence in comparison with other management options. SEARCH METHODS:
      We searched the Cochrane Incontinence Group Specialised Register, which contains
      trials identified from the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and
      handsearching of journals and conference proceedings (searched 12 November 2014),
      and the reference lists of relevant articles. SELECTION CRITERIA: Randomised or
      quasi-randomised trials that included needle suspension for the treatment of
      urinary incontinence. DATA COLLECTION AND ANALYSIS: At least two authors assessed
      trials and extracted data independently. Two trial investigators provided
      additional information. MAIN RESULTS: We identified 10 trials, which included 375
      women having six different types of needle suspension procedures and 489 who
      received comparison interventions. Needle suspensions were more likely to fail
      than open abdominal retropubic suspension. There was a higher subjective failure
      rate after the first year (91/313 (29%) failed versus 47/297 (16%) failed after
      open abdominal retropubic suspension). The risk ratio (RR) was 2.00 (95%
      confidence interval (CI) 1.47 to 2.72), although the difference in peri-operative
      complications was not significant (17/75 (23%) versus 12/77 (16%); RR 1.44, 95%
      CI 0.73 to 2.83). There were no significant differences for the other outcome
      measures. This effect was seen in both women with primary incontinence and women
      with recurrent incontinence after failed primary operations. Needle suspensions
      may be as effective as anterior vaginal repair (50/156 (32%) failed after needle
      suspension versus 64/181 (35%) after anterior repair; RR 0.86, 95% CI 0.64 to
      1.16), but there was little information about morbidity. Data for comparison with
      suburethral slings were inconclusive because they came from a small and atypical
      population.No trials compared needle suspensions with conservative management,
      peri-urethral injections, or sham or laparoscopic surgery. AUTHORS' CONCLUSIONS:
      Bladder neck needle suspension surgery is probably not as good as open abdominal
      retropubic suspension for the treatment of primary and secondary urodynamic
      stress incontinence because the cure rates were lower in the trials reviewed.
      However, the reliability of the evidence was limited by poor quality and small
      trials. There was not enough information to comment on comparisons with
      suburethral sling operations. Although cure rates were similar after needle
      suspension compared with after anterior vaginal repair, the data were
      insufficient to be reliable and inadequate to compare morbidity. A Brief Economic
      Commentary (BEC) identified no cost-effectiveness studies comparing bladder neck
      needle suspension with other surgeries.

PMID- 28742263
TI  - Progesterone receptor modulators for endometriosis.
AB  - BACKGROUND: Endometriosis is defined as the presence of endometrial tissue
      (glands and stroma) outside the uterine cavity. This condition is oestrogen
      dependent and thus is seen primarily during the reproductive years. Owing to
      their antiproliferative effects in the endometrium, progesterone receptor
      modulators (PRMs) have been advocated for treatment of endometriosis. OBJECTIVES:
      To assess the effectiveness and safety of PRMs primarily in terms of pain relief
      as compared with other treatments or placebo or no treatment in women of
      reproductive age with endometriosis. SEARCH METHODS: We searched the following
      electronic databases, trial registers, and websites: the Cochrane Gynaecology and
      Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central
      Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov,
      and the World Health Organization (WHO) platform, from inception to 28 November
      2016. We handsearched reference lists of articles retrieved by the search.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) published in
      all languages that examined effects of PRMs for treatment of symptomatic
      endometriosis. DATA COLLECTION AND ANALYSIS: We used standard methodological
      procedures as expected by the Cochrane Collaboration. Primary outcomes included
      measures of pain and side effects. MAIN RESULTS: We included 10 randomised
      controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus
      placebo or versus a different dose of mifepristone, one RCT compared asoprisnil
      versus placebo, one compared ulipristal versus leuprolide acetate, and four
      compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH)
      analogues, or a different dose of gestrinone. The quality of evidence ranged from
      high to very low. The main limitations were serious risk of bias (associated with
      poor reporting of methods and high or unclear rates of attrition in most
      studies), very serious imprecision (associated with low event rates and wide
      confidence intervals), and indirectness (outcome assessed in a select subgroup of
      participants). Mifepristone versus placebo One study made this comparison and
      reported rates of painful symptoms among women who reported symptoms at
      baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea
      (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n
      =352; moderate-quality evidence), suggesting that if 40% of women taking placebo
      experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone
      will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23,
      95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the
      mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea
      and 24% had hot flushes, although the placebo group reported only one event of
      each (1%) (high-quality evidence). Evidence was insufficient to show differences
      in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose
      comparisons Two studies compared doses of mifepristone and found insufficient
      evidence to show differences between different doses in terms of effectiveness or
      safety, if present. However, subgroup analysis of comparisons between
      mifepristone and placebo suggest that the 2.5 mg dose may be less effective than
      5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons
      Ons study compared gestrinone with danazol, and another study compared gestrinone
      with leuprolin.Evidence was insufficient to show differences, if present, between
      gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic
      pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality
      evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very
      low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n
      = 222; very low-quality evidence). The gestrinone group had a higher rate of
      hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality
      evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to
      0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show
      differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI
      0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95%
      CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).When researchers
      compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal
      rating scale (lower score denotes benefit), the mean dysmenorrhoea score was
      higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n =
      55; low-quality evidence), but the mean dyspareunia score was lower in this group
      (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group
      had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49;
      low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n
      = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92,
      95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).Evidence was
      insufficient to show differences in effectiveness or safety between different
      doses of gestrinone, if present. Asoprisnil versus placebo One study (n = 130)
      made this comparison but did not report data suitable for analysis. Ulipristal
      versus leuprolide acetate One study (n = 38) made this comparison but did not
      report data suitable for analysis. AUTHORS' CONCLUSIONS: Among women with
      endometriosis, moderate-quality evidence shows that mifepristone relieves
      dysmenorrhoea, and low-quality evidence suggests that this agent relieves
      dyspareunia, although amenorrhoea and hot flushes are common side effects. Data
      on dosage were inconclusive, although they suggest that the 2.5 mg dose of
      mifepristone may be less effective than higher doses. We found insufficient
      evidence to permit firm conclusions about the safety and effectiveness of other
      progesterone receptor modulators.

PMID- 28742264
TI  - Structural Revision and Biomimetic Synthesis of Goupiolone B.
AB  - Goupiolones A and B are unique phenolic compounds with significant DNA-damaging
      activity. In this study, the structure of goupiolone B was revised on the basis
      of DFT calculations of the 13 C NMR chemical shifts and biosynthetic
      considerations. The dibenzobicyclo[3.2.2]nonane skeleton of the revised structure
      suggested that goupiolone B was produced by oxidative coupling between catechol
      and goupiolone A, which was strongly supported by biomimetic synthesis.
      Furthermore, racemization of goupiolone B was observed during the attempted
      resolution of its racemic mixture. A plausible racemization mechanism involving
      alpha-ketol rearrangement is proposed.

PMID- 28742265
TI  - Congenital disorders of glycosylation: The Saudi experience.
AB  - We retrospectively reviewed Saudi patients who had a congenital disorder of
      glycosylation (CDG). Twenty-seven Saudi patients (14 males, 13 females) from 13
      unrelated families were identified. Based on molecular studies, the 27 CDG
      patients were classified into different subtypes: ALG9-CDG (8 patients, 29.5%),
      ALG3-CDG (7 patients, 26%), COG6-CDG (7 patients, 26%), MGAT2-CDG (3 patients,
      11%), SLC35A2-CDG (1 patient), and PMM2-CDG (1 patient). All the patients had
      homozygous gene mutations. The combined carrier frequency of CDG for the
      encountered founder mutations in the Saudi population is 11.5 per 10,000, which
      translates to a minimum disease burden of 14 patients per 1,000,000. Our study
      provides comprehensive epidemiologic information and prevalence figures for each
      of these CDG in a large cohort of congenital disorder of glycosylation patients.

PMID- 28742266
TI  - p-Coumaric acid, a dietary polyphenol ameliorates inflammation and curtails
      cartilage and bone erosion in the rheumatoid arthritis rat model.
AB  - This study was designed to explore the underlying mechanism of p-coumaric acid
      (CA), a dietary polyphenol in adjuvant-induced arthritis (AIA) rat model with
      reference to synovitis and osteoclastogenesis. Celecoxib (COX-2 selective
      inhibitor) (5 mg/kg b.wt) was used as a reference drug. CA remarkably suppressed
      the paw edema, body weight loss and inflammatory cytokine and chemokine levels
      (TNF-alpha, IL-1beta, IL-6, and MCP-1) in serum and ankle joint of arthritic
      rats. Consistently, CA reduced the expression of osteoclastogenic factors (RANKL
      and TRAP), pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, and IL-17), and
      inflammatory enzymes (iNOS and COX-2) in arthritic rats. However, OPG expression
      was found elevated. Besides, the abundance of transcription factors (NF-kappaB
      p65, and p-NF-kappaB-p65, NFATc-1, and c-Fos) and MAP kinases (JNK, p-JNK, and
      ERK1/2) expression was alleviated in CA administered arthritic rats. In addition,
      CA truncated osteoclastogenesis by regulating the RANKL/OPG imbalance in
      arthritic rats and suppressing the RANKL-induced NFATc-1 and c-Fos expression in
      vitro. Radiological (CT and DEXA scan) and histological assessments authenticated
      that CA inhibited TRAP, bone destruction and cartilage degradation in association
      with enhanced bone mineral density. Taken together, our findings suggest that CA
      demonstrated promising anti-arthritic effect and could prove useful as an
      alternative drug in RA therapeutics. (c) 2017 BioFactors, 43(5):698-717, 2017.

PMID- 28742267
TI  - Profiling the effects of short time-course cold ischemia on tumor protein
      phosphorylation using a Bayesian approach.
AB  - Phosphorylated proteins provide insight into tumor etiology and are used as
      diagnostic, prognostic, and therapeutic markers of complex diseases. However, pre
      analytic variations, such as freezing delay after biopsy acquisition, often occur
      in real hospital settings and potentially lead to inaccurate results. The
      objective of this work is to develop statistical methodology to assess the
      stability of phosphorylated proteins under short-time cold ischemia. We consider
      a hierarchical model to determine if phosphorylation abundance of a protein at a
      particular phosphorylation site remains constant or not during cold ischemia.
      When phosphorylation levels vary across time, we estimate the direction of the
      changes in each protein based on the maximum overall posterior probability and on
      the pairwise posterior probabilities, respectively. We analyze a dataset of
      ovarian tumor tissues that suffered cold-ischemia shock before the proteomic
      profiling. Gajadhar et al. (2015) applied independent clusterings for each
      patient because of the high heterogeneity across patients, while our proposed
      model shares information allowing conclusions for the entire sample population.
      Using the proposed model, 15 out of 32 proteins show significant changes during 1
      hour cold ischemia. Through simulation studies, we conclude that our proposed
      methodology has a higher accuracy for detecting changes compared to an order
      restricted inference method. Our approach provides inference on the stability of
      these phosphorylated proteins, which is valuable when using these proteins as
      biomarkers for a disease.

PMID- 28742268
TI  - Carbon Dioxide Capture by Aqueous Ionic Liquid Solutions.
AB  - Confined water in aqueous solutions of imidazolium-based ionic liquids (ILs)
      associated with acetate and imidazolate anions react reversibly with CO2 to yield
      bicarbonate. Three types of CO2 sorption in these "IL aqueous solutions" were
      observed: physical, CO2 -imidazolium adduct generation, and bicarbonate formation
      (up to 1.9 molbicarbonate  mol-1 of IL), resulting in a 10:1 (molar ratio) total
      absorption of CO2 relative to imidazolate anions in the presence of water 1:1000
      (IL/water). These sorption values are higher than the classical alkanol amines or
      even alkaline aqueous solutions under similar experimental conditions.

PMID- 28742269
TI  - Unilateral lung agenesis, aplasia or hypoplasia: Which one is it?

PMID- 28742270
TI  - Malignancy screening in autoimmune myositis among Australian rheumatologists.
AB  - BACKGROUND: The international literature advocates for cancer screening in newly
      diagnosed patients with autoimmune myositis; however, there is no widely accepted
      consensus or guideline to outline the optimal cancer screening strategy and the
      evidence is currently insufficient to support any recommendation. AIM: Our study
      aimed to establish the current trends in practice in malignancy screening in
      autoimmune myositis among Australian rheumatologists. METHODS: All
      rheumatologists who were full members of the Australian Rheumatology Association
      in 2016 (386) were invited to complete an online questionnaire. Respondent
      demographics and information on screening approach and concerns were collected
      using multiple choice and open-response questions. There were 60 respondents (16%
      response rate). All available quantitative data were analysed and reported using
      statistical software. Qualitative data were analysed and grouped according to
      themes. RESULTS: Most respondents (93%) performed cancer screening. Significant
      variation was found in terms of approach to patient selection, choice of
      screening test, delegation of screening and repeat screening. A lack of clinical
      practice consensus and guideline (77%), test selection knowledge (37%), knowledge
      on repeated screening (53%) and the potential for harm (62%) were identified
      challenges in this area. CONCLUSION: Malignancy screening in autoimmune myositis
      was variable among this small cohort of Australian rheumatologists. The observed
      differences were driven by patient factors and clinician preferences. The group
      identified several challenges in the cancer screening process. Further research
      is warranted to address these challenges, close the evidence gap and develop
      workable guidelines.

PMID- 28742271
TI  - Genetic-genealogy approach reveals low rate of extrapair paternity in historical
      Dutch populations.
AB  - OBJECTIVE: Evolutionary theory has shown that seeking out extrapair paternity
      (EPP) can be a viable reproductive strategy for both sexes in pair-bonded
      species, also in humans. As yet, estimates of the contemporary or historical EPP
      rate in human population are still rare. In the present study, we estimated the
      historical EPP rate in the Dutch population over the last 400 years and compared
      the rate with those obtained for other human populations to determine the
      evolutionary, cultural, and socio-demographic factors that influence human
      cuckoldry behavior. METHODS: We estimated the historical EPP rate for the Dutch
      population via the "genealogical pair method", in which the EPP rate is derived
      from Y-chromosome mismatches between pairs of individuals that, based on
      genealogical evidence, share a common paternal ancestor. RESULTS: Based on the
      analysis of 68 representative genealogical pairs, separated by a total of 1013
      fertilization events, we estimated that the historical EPP rate for the Dutch
      population over the last 400 years was 0.96% per generation (95% confidence
      interval 0.46%-1.76%). CONCLUSION: The Dutch EPP rate fits perfectly within the
      range reported for other contemporary and historical populations in Western
      Europe and was highly congruent with that estimated for neighboring Flanders,
      despite the socio-economic and religious differences between both populations.
      The estimated low EPP rate challenges the "dual mating strategy hypothesis" that
      states that women could obtain fitness benefits by securing investment from one
      man while cuckolding him to obtain good genes from an affair partner.

PMID- 28742272
TI  - Longitudinal associations between exercise identity and exercise motivation: A
      multilevel growth curve model approach.
AB  - Past work linking exercise identity and exercise motivation has been cross
      sectional. This is the first study to model the relations between different types
      of exercise identity and exercise motivation longitudinally. Understanding the
      dynamic associations between these sets of variables has implications for theory
      development and applied research. This was a longitudinal survey study.
      Participants were 180 exercisers (79 men, 101 women) from Greece, who were
      recruited from fitness centers and were asked to complete questionnaires
      assessing exercise identity (exercise beliefs and role-identity) and exercise
      motivation (intrinsic, identified, introjected, external motivation, and
      amotivation) three times within a 6 month period. Multilevel growth curve
      modeling examined the role of motivational regulations as within- and between
      level predictors of exercise identity, and a model in which exercise identity
      predicted exercise motivation at the within- and between-person levels. Results
      showed that within-person changes in intrinsic motivation, introjected, and
      identified regulations were positively and reciprocally related to within-person
      changes in exercise beliefs; intrinsic motivation was also a positive predictor
      of within-person changes in role-identity but not vice versa. Between-person
      differences in the means of predictor variables were predictive of initial levels
      and average rates of change in the outcome variables. The findings show support
      to the proposition that a strong exercise identity (particularly exercise
      beliefs) can foster motivation for behaviors that reinforce this identity. We
      also demonstrate that such relations can be reciprocal overtime and can depend on
      the type of motivation in question as well as between-person differences in
      absolute levels of these variables.

PMID- 28742273
TI  - Protein secondary structure analysis of dried blood serum using infrared
      spectroscopy to identify markers for colitis screening.
AB  - There remains a great need for diagnosis of inflammatory bowel disease, for which
      the current technique, colonoscopy, is costly and also has risks for
      complications. Attenuated total reflectance Fourier transform infrared
      spectroscopy is a new screening technique to evaluate colitis. Using second
      derivative spectral deconvolution of the absorbance spectra, a full set of
      spectral markers were identified based on statistical analysis. Using this
      method, Amide I group frequencies, (specifically, alpha-helix to beta-sheet ratio
      of the protein secondary structure) were identified in addition to the previously
      reported glucose and mannose signatures in sera of chronic and acute mice models
      of colitis. We also used the same technique to demonstrate that these spectral
      markers (alpha-helix/beta-sheet ratio, glucose and mannose) are recovering to
      basal levels upon anti-TNFalpha therapy. Hence, this technique will be able to
      identify changes in the sera due to diseases.

PMID- 28742274
TI  - Whole exome sequencing identified genetic variations in Chinese hemangioblastoma
      patients.
AB  - Hemangioblastomas (HBs) are uncommon tumors characterized by the presence of
      inactivating alterations in the von Hippel-Lindau (VHL) gene in inherited cases
      and by infrequent somatic mutation in sporadic entities. We performed whole exome
      sequencing on 11 HB patients to further elucidate the genetics of HBs. A total of
      270 somatic variations in 219 genes, of which there were 86 mutations in 67
      genes, were found in sporadic HBs, and 184 mutations were found in 154 genes in
      familial HBs. C: G>T: A and T: A>C: G mutations are relatively common in most HB
      patients. Genes harboring the most significant mutations include PCDH9, KLHL12,
      DCAF4L1, and VHL in sporadic HBs, and ZNF814, DLG2, RIMS1, PNN, and MUC7 in
      familial HBs. The frequency of CNV varied considerably within sporadic HBs but
      was relatively similar within familial HBs. Five genes, including OTOGL, PLCB4,
      SCEL, THSD4, and WWOX, have CNVs in the six patients with sporadic HBs, and three
      genes, including ABCA6, CWC27, and LAMA2, have CNVs in the five patients with
      familial HBs. We found new genetic mutations and CNVs that might be involved in
      HBs; these findings highlight the complexity of the tumorigenesis of HBs and
      pinpoint potential therapeutic targets for the treatment of HBs.

PMID- 28742276
TI  - Heteronomy in the arts field: state funding and British arts organizations.
AB  - For Bourdieu, the field of cultural production is comprised of an autonomous and
      a heteronomous sector. A heteronomous sector is one that is interpenetrated by
      the commercial field. I discuss an arena that, until recently, was part of the
      relatively autonomous sector in the field of cultural production - the supported
      arts sector in the United Kingdom - and argue that it became more heteronomous,
      due to the penetration by the state. Heteronomy due to the commercial field is
      present but secondary to, and driven by, the actions of the state. Political
      parties' attempts to diffuse and legitimate a particular economic ideology have
      led to state demands that arts institutions adopt neoliberal business practices
      in exchange for funding. Government giving to the arts, previously at arm's
      length, proved to be a Faustian bargain that demanded significant repayment in
      the form of lost autonomy. Coercive pressures from the state, enacted over time,
      show how the domination of one field over another can occur, even when the
      domination is resisted.

PMID- 28742275
TI  - The proteome and transcriptome of the infectious metacyclic form of Trypanosoma
      brucei define quiescent cells primed for mammalian invasion.
AB  - The infectious metacyclic forms of Trypanosoma brucei result from a complex
      development in the tsetse fly vector. When they infect mammals, they cause
      African sleeping sickness in humans. Due to scarcity of biological material and
      difficulties of the tsetse fly as an experimental system, very limited
      information is available concerning the gene expression profile of metacyclic
      forms. We used an in vitro system based on expressing the RNA binding protein 6
      to obtain infectious metacyclics and determined their protein and mRNA
      repertoires by mass-spectrometry (MS) based proteomics and mRNA sequencing (RNA
      Seq) in comparison to non-infectious procyclic trypanosomes. We showed that
      metacyclics are quiescent cells, and propose this influences the choice of a
      monocistronic variant surface glycoprotein expression site. Metacyclics have a
      largely bloodstream-form type transcriptome, and thus are programmed to translate
      a bloodstream-form type proteome upon entry into the mammalian host and
      resumption of cell division. Genes encoding cell surface components showed the
      largest changes between procyclics and metacyclics, observed at both the
      transcript and protein levels. Genes encoding metabolic enzymes exhibited
      expression in metacyclics with features of both procyclic and bloodstream forms,
      suggesting that this intermediate-type metabolism is dictated by the availability
      of nutrients in the tsetse fly vector.

PMID- 28742277
TI  - Immediate and short-term effects of real-time knee adduction moment feedback on
      the peak and cumulative knee load during walking.
AB  - The peak external knee adduction moment (pKAM), KAM impulse, and peak knee
      flexion moment (pKFM) during gait are important loading variables in medial
      tibiofemoral osteoarthritis. We evaluated the effects of gait modification, using
      real-time pKAM visual feedback, on pKAM, KAM impulse, and pKFM; and whether
      participants could maintain the KAM-reducing gait after feedback removal. Eleven
      healthy individuals performed a series of walking trials on a split-belt
      instrumented treadmill under four conditions of Baseline, Feedback, No Feedback
      Early, and No Feedback Late. Guided by real-time feedback of pKAM, they modified
      their gait patterns to lower pKAM by 20%. Three-dimensional joint
      kinematics/kinetics during each walking condition were recorded by a 12-camera
      motion capture system and the instrumented treadmill. Change in each knee loading
      parameter from baseline across conditions was assessed using one-way repeated
      measures analysis-of-variances. In the feedback limb, successful 20% reductions
      from baseline in pKAM and KAM impulse were achieved across all three conditions.
      There was a trend for concomitant pKFM increases, partially attenuating the
      beneficial effects of pKAM reduction. A carry-over effect of KAM reduction in the
      non-feedback limb was noted. The altered gait patterns were participant-specific
      and multi-modal; each participant reported a combination of two to three gait
      modification strategies used for pKAM reduction. Toe-in and medial foot contact
      were the most reported strategies. The findings support the real-time pKAM visual
      feedback as a tool for individualized gait modification to reduce knee load.
      Future studies to evaluate its effectiveness in persons with or at risk for
      medial knee osteoarthritis is warranted. (c) 2017 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 36:397-404, 2018.

PMID- 28742278
TI  - Agenesis of the corpus callosum, developmental delay, autism spectrum disorder,
      facial dysmorphism, and posterior polymorphous corneal dystrophy associated with
      ZEB1 gene deletion.
AB  - We report on a girl diagnosed prenatally with agenesis of the corpus callosum
      (ACC) on fetal ultrasound and MRI. On postnatal follow-up she was noted to have
      developmental delay, facial dysmorphism, autism spectrum disorder, and posterior
      polymorphous corneal dystrophy (PPD). Array-comparative genomic hybridization
      analysis (Array-CGH) showed a 2.05 Mb de novo interstitial deletion at
      10p11.23p11.22. The deleted region overlaps 1 OMIM Morbid Map gene, ZEB1 (the
      zinc finger E-box binding homeobox transcription factor 1), previously associated
      with posterior polymorphous corneal dystrophy type 3 (PPCD3). To our best
      knowledge this is the first reported case with a deletion of the ZEB1 gene in an
      individual with ACC and PPD, showing that the haploinsufficiency of the ZEB1 is
      likely the cause of our patient's phenotype.

PMID- 28742279
TI  - Additional report on Moreno-Nishimura-Schmidt overgrowth syndrome.

PMID- 28742280
TI  - Clinical outcomes in patients with advanced epidermal growth factor receptor
      mutated non-small-cell lung cancer in South Western Sydney Local Health District.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR)-mutated non-small-cell lung
      cancer (NSCLC) is a subgroup of oncogene addicted lung cancer that predicts
      response to tyrosine kinase inhibitors (TKI). However, there is variability in
      response and survival outcomes in patients with EGFR mutation treated with TKI.
      AIM: To describe clinical characteristics, treatment patterns and factors
      influencing outcomes in patients with EGFR-mutated NSCLC in South Western Sydney
      Local Health District. METHODS: Retrospective review of patients with EGFR
      mutated NSCLC diagnosed between January 2010 and June 2016. RESULTS: A total of
      85 EGFR-mutated NSCLC patients was identified; 80 (94%) received first-line
      treatment with EGFR-TKI. The median follow-up was 10.7 months with a median
      duration of treatment of 9 months. On disease progression (n = 44), 37% had best
      supportive care only, 30% received chemotherapy, 23% participated in clinical
      trials, 7% continued on a first generation EGFR-TKI and 3% received afatinib.
      Overall response rate to first-line EGFR-TKI was 66%. Median progression-free
      survival (PFS) was 10.7 months (range 2.7-55.9 months) and median overall
      survival (OS) was 23 months (range 0.4-35.8 months). Multivariate Cox regression
      analysis showed that patients with lower disease burden (<4 sites) had longer PFS
      (hazard ratio (HR) 0.36, 95% confidence interval (CI) 0.18-0.72, P = 0.004) but
      not OS. Good performance status predicts longer OS (HR 0.33, CI 0.14-0.77, P =
      0.01). Lower (<5) pre-treatment neutrophil-to-lymphocyte ratio (NLR) was
      associated with better PFS (HR 0.40, 95% CI 0.18-0.87, P = 0.02) and OS (HR 0.43,
      95% CI 0.19-0.94, P = 0.04). There were no survival differences when patients
      were stratified by age, baseline albumin level and types of EGFR mutation.
      CONCLUSION: Results from this community-based cohort confirm known prognostic
      factors in patients with EGFR-mutated NSCLC receiving TKI and suggest the
      negative influence of a heightened host systemic inflammatory response on patient
      outcomes.

PMID- 28742281
TI  - Structured identification of response options to address environmental health
      risks at the Agbogbloshie electronic waste site.
AB  - Electronic waste (e-waste) is a growing problem across low- and middle-income
      countries. Agbogbloshie (Accra, Ghana) is among the world's largest and most
      notorious e-waste sites, with an increasing number of studies documenting a range
      of environmental health risks. The present study aimed to provide national,
      regional, and international stakeholders with a summary of expert opinion on the
      most pressing problems arising from e-waste activities at Agbogbloshie, as well
      as suggested solutions to address these problems. Structured interviews were
      performed between April and September 2015 that used a Logical Framework Approach
      as a scoping exercise to gauge problems and benefits of e-waste recycling, and
      the Delphi methodology to identify response options. Stakeholders (n = 19) from
      15 institutions were interviewed with 2 rounds of a Delphi Poll: open-ended
      interviews followed by an electronic questionnaire in which experts ranked
      various proposed response options based on health, environmental, social, and
      economic benefit and feasibility. The goal was to prioritize potential
      interventions that would address identified problems at Agbogbloshie. Experts
      identified the most beneficial and feasible options in decreasing rank order as
      follows and prefaced by the statement "it is recommended that": 1) there be
      further research on the health effects; 2) e-waste workers be given appropriate
      personal protective equipment; 3) the Ministry of the Environment, Science,
      Technology and Innovation re-visit Ghana's Hazardous Waste Bill; 4) e-waste
      workers be involved in the planning process of interventions and are be kept
      informed of any results; and 5) there be increased education and sensitization on
      hazards related to e-waste for both workers and the general public. These
      solutions are discussed in relation to ongoing dialogue at the international
      level concerning e-waste recycling interventions, with strengths and weaknesses
      examined for the Ghanaian context. Integr Environ Assess Manag 2017;13:980-991.
      (c)2017 SETAC.

PMID- 28742282
TI  - MED resulting from recessively inherited mutations in the gene encoding calcium
      activated nucleotidase CANT1.
AB  - Multiple Epiphyseal Dysplasia (MED) is a relatively mild skeletal dysplasia
      characterized by mild short stature, joint pain, and early-onset
      osteoarthropathy. Dominantly inherited mutations in COMP, MATN3, COL9A1, COL9A2,
      and COL9A3, and recessively inherited mutations in SLC26A2, account for the
      molecular basis of disease in about 80-85% of the cases. In two families with
      recurrent MED of an unknown molecular basis, we used exome sequencing and
      candidate gene analysis to identify homozygosity for recessively inherited
      missense mutations in CANT1, which encodes calcium-activated nucleotidase 1. The
      MED phenotype is thus allelic to the more severe Desbuquois dysplasia phenotype
      and the results identify CANT1 as a second locus for recessively inherited MED.

PMID- 28742283
TI  - Reliability of visual and instrumental color matching.
AB  - OBJECTIVE: The aim of this investigation was to evaluate intra-rater and inter
      rater reliability of visual and instrumental shade matching. MATERIALS AND
      METHODS: Forty individuals with normal color perception participated in this
      study. The right maxillary central incisor of a teaching model was prepared and
      restored with 10 feldspathic all-ceramic crowns of different shades. A shade
      matching session consisted of the observer (rater) visually selecting the best
      match by using VITA classical A1-D4 (VC) and VITA Toothguide 3D Master (3D) shade
      guides and the VITA Easyshade Advance intraoral spectrophotometer (ES) to obtain
      both VC and 3D matches. Three shade matching sessions were held with 4 to 6 weeks
      between sessions. Intra-rater reliability was assessed based on the percentage of
      agreement for the three sessions for the same observer, whereas the inter-rater
      reliability was calculated as mean percentage of agreement between different
      observers. The Fleiss' Kappa statistical analysis was used to evaluate visual
      inter-rater reliability. RESULTS: The mean intra-rater reliability for the visual
      shade selection was 64(11) for VC and 48(10) for 3D. The corresponding ES values
      were 96(4) for both VC and 3D. The percentages of observers who matched the same
      shade with VC and 3D were 55(10) and 43(12), respectively, while corresponding ES
      values were 88(8) for VC and 92(4) for 3D. CONCLUSIONS: The results for visual
      shade matching exhibited a high to moderate level of inconsistency for both intra
      rater and inter-rater comparisons. The VITA Easyshade Advance intraoral
      spectrophotometer exhibited significantly better reliability compared with visual
      shade selection. CLINICAL SIGNIFICANCE: This study evaluates the ability of
      observers to consistently match the same shade visually and with a dental
      spectrophotometer in different sessions. The intra-rater and inter-rater
      reliability (agreement of repeated shade matching) of visual and instrumental
      tooth color matching strongly suggest the use of color matching instruments as a
      supplementary tool in everyday dental practice to enhance the esthetic outcome.

PMID- 28742284
TI  - Aquatic animals promote antibiotic resistance gene dissemination in water via
      conjugation: Role of different regions within the zebra fish intestinal tract,
      and impact on fish intestinal microbiota.
AB  - The aqueous environment is one of many reservoirs of antibiotic resistance genes
      (ARGs). Fish, as important aquatic animals which possess ideal intestinal niches
      for bacteria to grow and multiply, may ingest antibiotic resistance bacteria from
      aqueous environment. The fish gut would be a suitable environment for conjugal
      gene transfer including those encoding antibiotic resistance. However, little is
      known in relation to the impact of ingested ARGs or antibiotic resistance
      bacteria (ARB) on gut microbiota. Here, we applied the cultivation method, qPCR,
      nuclear molecular genetic marker and 16S rDNA amplicon sequencing technologies to
      develop a plasmid-mediated ARG transfer model of zebrafish. Furthermore, we aimed
      to investigate the dissemination of ARGs in microbial communities of zebrafish
      guts after donors carrying self-transferring plasmids that encode ARGs were
      introduced in aquaria. On average, 15% of faecal bacteria obtained ARGs through
      RP4-mediated conjugal transfer. The hindgut was the most important intestinal
      region supporting ARG dissemination, with concentrations of donor and
      transconjugant cells almost 25 times higher than those of other intestinal
      segments. Furthermore, in the hindgut where conjugal transfer occurred most
      actively, there was remarkable upregulation of the mRNA expression of the RP4
      plasmid regulatory genes, trbBp and trfAp. Exogenous bacteria seem to alter
      bacterial communities by increasing Escherichia and Bacteroides species, while
      decreasing Aeromonas compared with control groups. We identified the composition
      of transconjugants and abundance of both cultivable and uncultivable bacteria
      (the latter accounted for 90.4%-97.2% of total transconjugants). Our study
      suggests that aquatic animal guts contribute to the spread of ARGs in water
      environments.

PMID- 28742285
TI  - Variable expressivity and incomplete penetrance in a large family with non
      classical Diamond-Blackfan anemia associated with ribosomal protein L11 splicing
      variant.
AB  - Diamond-Blackfan anemia (DBA) is a group of clinically and genetically
      heterogeneous bone marrow failure disorders with or without congenital anomalies.
      Variable expressivity and incomplete penetrance have been observed within
      affected families. Diamond-Blackfan anemia-7 (DBA7), caused by heterozygous
      mutations in ribosomal protein L11 (RPL11), accounts for approximately 5% of DBA.
      DBA7 is usually characterized by early-onset bone marrow failure often
      accompanied by congenital malformations, especially thumb defects. Here, we
      present the case of a 2-year-old boy with chronic mild normocytic anemia, short
      stature, bilateral underdevelopment of the thumbs, atrial septal defect, and
      hypospadias. Hematological testing revealed slightly decreased hematocrit and
      hemoglobin, normal HbF, and elevated eADA. Family history included maternal
      relatives with thumb defects, but the mother's thumbs were normal. Clinical exome
      sequencing detected a maternally-inherited RPL11 variant, c.396+3A>G, that is
      predicted to affect splicing. A family correlation study of the identified
      variant demonstrates segregation with thumb anomalies in the mother's family. RNA
      studies suggest that the variant produces an alternative transcript that is
      likely susceptible to nonsense-mediated decay. This report summarizes the
      prevalence of non-anemia findings in DBA7 and describes a non-classical familial
      presentation of DBA7 more associated with thumb anomalies than with anemia.

PMID- 28742286
TI  - Evaluation of systemic absorption and renal effects of topical ophthalmic
      flurbiprofen and diclofenac in healthy cats.

PMID- 28742287
TI  - Quality of Life of Intermittent Urinary Catheterization Users and Their
      Caregivers: A Scoping Review.
AB  - AIMS: This study aimed to examine and map the scientific evidences regarding
      quality of life in neurogenic bladder patients and consequently their caregivers
      by means of a scoping review. DESIGN: This is a scoping review proposal of the
      Joanna Briggs Institute. METHODS: It was conducted to examine and map the
      scientific evidences about quality of life (QoL) in neurogenic bladder patients
      and their caregivers, to identify the meanings attributed to QoL and its relation
      with intermittent urinary catheterization. The following guiding question was:
      "What scientific evidence has been produced on the QoL of neurogenic bladder
      patients using intermittent urinary catheterization and their caregivers?" A
      total of 2945 research studies were identified using The Cochrane Library,
      CINAHL, LILACS, Academic Search Premier (via EBSCO platform), PubMed, SCOPUS, the
      platforms Web of Science, the b-on and Gray Literature. The keywords established
      were patient, intermittent urinary catheterization, neurogenic urinary bladder,
      quality of life and caregiver. RESULTS: From 2,945 studies, 13 studies were
      selected. Most of the selected studies that analyzed variables related to the
      patients' QoL were regarding the urinary catheterization technique, assessment of
      urinary incontinence, individual perceptions of the procedure and experiences
      with urinary catheter in childhood and adult life. The meanings attributed to
      QoL, when compared to adult and child individuals with normal bladder
      functioning, presented lower QoL scores. Concerning caregivers, the QoL of
      caregivers of children using intermittent urinary catheterization demonstrated
      low scores. LINKING EVIDENCE TO ACTION: The QoL of patient's who use intermittent
      urinary catheterization can be determined by improvement of urinary symptoms and
      self-confidence. Research related to QoL of patients who use urinary catheter
      indicates the importance of adequate professional support and appropriate health
      public policies.

PMID- 28742288
TI  - Supporting and Empowering Direct-Care Nurses to Promote EBP: An Example of
      Evidence-Based Policy Development, Education, and Practice Change.
AB  - This column shares the best evidence-based strategies and innovative ideas on how
      to facilitate the learning and implementation of EBP principles and processes by
      clinicians as well as nursing and interprofessional students. Guidelines for
      submission are available at
      http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1741-6787.

PMID- 28742289
TI  - Tai Chi Exercise for the Quality of Life in a Perimenopausal Women Organization:
      A Systematic Review.
AB  - BACKGROUND: Improvement of the quality of life in perimenopausal women has
      recently become an important global health issue. Extensive research reports
      provide evidence of Tai Chi for the quality of life, but no systematic review has
      individually investigated Tai Chi as a main intervention on the quality of life
      in perimenopausal women. OBJECTIVE: To assess clinical evidence of Tai Chi for
      the quality of life in perimenopausal women. METHODS: Studies related to the
      effect of Tai Chi on the quality of life in perimenopausal women in the databases
      of China and abroad were searched. RevMan version 5.2 software was used, and the
      Medical Outcomes Study 36-item short form health survey (SF-36) and bone mineral
      density (BMD) were selected as evaluation indices. RESULTS: Five trials were
      included. The results of this study showed that Tai Chi had a significant effect
      on bodily pain, general health, vitality, mental health of SF-36, and the spine
      dimension of BMD, as supported by the following data: bodily pain (Standard Mean
      Difference [SMD] = -3.63; 95% confidence interval [CI] [-6.62, -0.64]; p = .02);
      general health (SMD = -5.08; 95% CI [-7.60, -2.56]; p < .0001); vitality (SMD = 
      5.67; 95% CI [-8.54, -2.81], p = .0001); mental health (SMD = -2.51; 95% CI [
      4.82, -0.20], p = .03); and spine dimension of BMD (SMD = -0.06; 95% CI [-0.10, 
      0.01]; p = .01). However, Tai Chi had no effect on physical function, emotional
      health, social function, role-physical of SF-36, and the hip dimension of BMD, as
      supported by the following data: physical function (SMD = -1.79; 95% CI [-5.15,
      1.57]; p = .30); emotional health (SMD = -2.90; 95% CI [-7.23, 1.43], p = .19];
      social function (SMD = -2.23, 95% CI [-5.08, 0.61], p = .12; role-physical (SMD =
      - 1.18; 95% CI [-4.84, 2.47], p = .53; and hip dimension of BMD (SMD = -0.01; 95%
      CI [-0.03, 0.01]; p = .31). LINKING EVIDENCE TO ACTION: This systematic review
      found significant evidence for Tai Chi improving bodily pain, general health,
      vitality, mental health of SF-36, and the spine dimension of BMD in patients with
      perimenopausal syndrome. Findings suggest that Tai Chi might be recommended as
      effective and safe adjuvant treatment for patients with perimenopausal syndrome.
      More high-quality randomized controlled trials are urgently needed to confirm
      these results.

PMID- 28742290
TI  - Infant-Related Intrusive Thoughts of Harm in the Postpartum Period: A Critical
      Review.
AB  - BACKGROUND: Besides the expected warm and joyful thoughts, a new mother can be
      disturbed by sudden frightening thoughts or images of harm done to her baby:
      harming intrusions, an obsessive phenomenon. Its high prevalence and possible
      consequences in functioning and in mother-child bonding makes it desirable that
      clinicians are well informed regarding the current state of knowledge about
      harming intrusions. OBJECTIVE: To provide a comprehensive review of all studies
      that have investigated harming intrusions in postpartum women. DATA SOURCES: A
      systematic search was performed for primary (MEDLINE, PsycINFO) and secondary
      (Cochrane Library, National Guideline Clearinghouse, American Psychiatric
      Association) literature, with data range from inception to April 2015. To provide
      a complete overview, the approach of the topic by Medical Subject Headings (MeSH)
      terms and keywords was broad. STUDY SELECTION: Studies in Dutch or English with a
      clear description of method, covering 1 of our main domains of interest
      prevalence, assessment, differential diagnosis, etiology, consequences, and
      treatment-were selected. DATA EXTRACTION: Two authors extracted quantitative and
      qualitative data fitting in the domains of interest. RESULTS AND CONCLUSIONS:
      Fifty articles were included. The prevalence of harming intrusions is up to 100%
      in both women with and without psychiatric disorders. Stress and cognitive
      misinterpretation are important keys in its appearance and severity. Literature
      consistently states that isolated harming intrusions contain no increased risk of
      violence; instead, compulsive behavior is very common. Psychoeducation is found
      to release a lot of distress; so might cognitive-behavioral therapy and
      psychotropic medications.

PMID- 28742291
TI  - Evaluating the Effect of the Changes in FDA Guidelines for Clozapine Monitoring.
AB  - BACKGROUND: Concerns exist that clozapine is underutilized in the management of
      treatment-resistant schizophrenia. Although a 2015 change in the US Food and Drug
      Administration (FDA) monitoring recommendations lowered the threshold of the
      absolute neutrophil count for treatment interruption from 1,500/MUL to 1,000/MUL
      and removed white blood cell count thresholds from the monitoring algorithm, the
      implications of this policy change on clozapine interruptions remain unknown.
      METHODS: We analyzed outpatient prescribing records for antipsychotic medications
      in the Veterans Integrated Service Network 7 (VISN 7) database between 1999 and
      2012 to assess the potential impact of the recent changes in FDA neutropenia
      monitoring recommendations on clozapine treatment discontinuation. We evaluated
      results of complete blood count monitoring to compare percentages of patients who
      developed or would have developed >= 1 hematologic event under the previous and
      current FDA guidelines in the first year following initiation of clozapine.
      RESULTS: From a cohort of 14,620 patients with schizophrenia (ICD-9-295.x), 246
      patients received clozapine treatment (1.7%). No agranulocytosis was observed
      during the study period. Under the former recommendations, 5 patients in the
      clozapine initiation cohort (n = 160, 3.1%; 95% CI, 0.43-5.83) qualified for
      treatment interruption during the first year of clozapine treatment, while only 1
      patient (0.6%) qualified under the current recommendations. Under the former
      recommendations, hematologic events occurred at a similar rate for individuals
      taking and not taking clozapine. CONCLUSIONS: While clozapine remains an
      underused medication, the new FDA monitoring guidelines are likely to
      substantially reduce the percentage of patients who meet criteria for clozapine
      associated hematologic events requiring treatment interruption. This decrease may
      reduce the clinical burden of managing patients on clozapine and therefore
      increase the number of individuals treated with this uniquely effective
      medication. However, prospective studies of individuals treated under the new
      guidelines are needed to fully assess safety of the FDA's change.

PMID- 28742293
TI  - Saliva May Have Disease-Detecting 'Fingerprints'.

PMID- 28742292
TI  - Effects of a Course of Right Unilateral Ultrabrief Pulse Electroconvulsive
      Therapy Combined With Venlafaxine on Insomnia Symptoms in Elderly Depressed
      Patients.
AB  - OBJECTIVE: Antidepressant medications have a variety of effects on sleep, apart
      from their antidepressant effects. It is unknown whether electroconvulsive
      therapy (ECT) has effects on perceived sleep in depressed patients. This
      secondary analysis examines the effects of ECT on perceived sleep, separate from
      its antidepressant effects. METHODS: Elderly patients with major depressive
      disorder, as defined by DSM-IV, received open-label high-dose, right unilateral
      ultrabrief pulse ECT, combined with venlafaxine, as part of participating in
      phase 1 of the National Institute of Mental Health-supported study Prolonging
      Remission in Depressed Elderly (PRIDE). Phase 1 of PRIDE participant enrollment
      period extended from February 2009 to August 2014. Depression severity was
      measured with the Hamilton Depression Rating Scale-24 item (HDRS24), and measures
      of insomnia severity were extracted from the HDRS24. Participants were
      characterized at baseline as either "high-insomnia" or "low-insomnia" subtypes,
      based upon the sum of the 3 HDRS24 sleep items as either 4-6 or 0-3,
      respectively. Insomnia scores were followed during ECT and were adjusted for the
      sum of all the HDRS24 non-sleep items. Generalized linear models were used for
      longitudinal analysis of insomnia scores. RESULTS: Two hundred forty patients
      participated, with 48.3% in the high-insomnia and 51.7% in the low-insomnia
      group. Although there was a reduction in the insomnia scores in the high-insomnia
      group, only 12.4% of them experienced remission of insomnia after a course of
      ECT, despite an increase in utilization of sleep aids across the course of ECT,
      from 8.6% to 23.2%. The degree of improvement in insomnia symptoms paralleled the
      degree of improvement in non-insomnia symptoms. A "low" amount of improvement on
      the sum of the HDRS non-insomnia items (HDRS-sleep) was accompanied by a "low"
      amount of improvement in insomnia scores (change of -1.6 +/- 1.2, P < .0001),
      while a "high" amount of improvement on the sum of the HDRS non-insomnia items
      was accompanied by a "higher" amount of improvement in insomnia scores (change of
      -3.1 +/- 1.6, P < .0001). After adjustment for non-insomnia symptoms, there was
      no change in insomnia in the low-insomnia group. CONCLUSIONS: We found that ECT,
      combined with venlafaxine, has a modest anti-insomnia effect that is linked to
      its antidepressant effect. Most patients will have some degree of residual
      insomnia after ECT, and will require some consideration of whether additional,
      targeted assessment and treatment of insomnia is warranted. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01028508.

PMID- 28742294
TI  - Oral and Systemic DiseasesYou May EncounterThroughout Your Career.

PMID- 28742295
TI  - Common Oral Manifestationsof Select Systemic Diseases:Anemia, Diabetes
      Mellitusand HIV.
AB  - In this article, we discuss several common abnormal signs andsymptoms that may be
      present in the oral cavity initially with or without anysystemic symptoms at a
      typical dental practice. The purpose of this discussion is toincrease clinical
      awareness for establishing differential diagnoses so that patientsmay obtain
      appropriate referrals for appropriate medical treatment.

PMID- 28742296
TI  - Mucocutaneous Diseases:Oral Lichen Planus, MucousMembrane Pemphigoid andPemphigus
      Vulgaris.
AB  - Mucocutaneous diseases affect the oral cavity and can presenta diagnostic
      challenge. They can have systemic involvement, necessitatingmultidisciplinary
      management. Frequently, patients will see their general dentistsinitially for
      evaluation. A better understanding of mucocutaneous diseases canprevent delay in
      appropriate diagnosis and treatment. Oral lichen planus, mucousmembrane
      pemphigoid and pemphigus vulgaris are three mucocutaneous diseasesthat affect the
      oral mucosa. This review describes the clinical features, epidemiology,etiology,
      pathogenesis and management for each condition.

PMID- 28742297
TI  - Less Common Oral Diseasesof Medical Significance.
AB  - The oral cavity is frequently involved in conditions that affectthe skin or other
      multi-organ diseases. In many instances, oral involvementprecedes the appearance
      of other symptoms or lesions at other locations.Anatomically, the mouth is easily
      accessible. An astute dental provider hasthe opportunity to observe physical and
      oral conditions that might includeundiagnosed or poorly managed systemic disease.
      This article reviews fourless common oral disease of medical significance.

PMID- 28742298
TI  - Acromegaly: A Dental Disease?
AB  - Acromegaly is a serious disease that affects the pituitary gland causingunusual
      growth in patients. There are various dental manifestation of the conditionand it
      is plausible that a dentist will be the first to recognize the problem. This
      articledescribes the disease and the dental implications for patients who have
      it.

PMID- 28742299
TI  - Hiring Done Right: License Verification andBackground Checks.

PMID- 28742300
TI  - HIPAA Privacy Tips and Reminders.

PMID- 28742305
TI  - Pediatric heat-related illness: recommendations for prevention and management
AB  - Infants, children, and adolescents are at increased risk for heat-related illness
      due to their inability to remove themselves from dangerous environments. Evidence
      shows that morbidity and mortality from heat illness is related to the length of
      time core temperature is elevated, so rapid reduction and accurate serial
      measurements are crucial to prevention of organ system damage and death. The
      primary methods of patient cooling are conduction (ice-water immersion, cold
      packs) and convection (moisture and moving air). The choice of method used may
      depend on availability of equipment, but there is evidence that can guide optimal
      use of resources. This issue presents evidence-based recommendations and best
      practices in heat-illness resuscitation, including managing children who are
      obese, have special needs or take medications, and advocacy for prevention
      strategies.

PMID- 28742306
TI  - Identifying emergency department patients with chest pain who are at low risk for
      acute coronary syndromes [digest].
AB  - Though a minority of patients presenting to the emergency department with chest
      pain have acute coronary syndromes,identifying the patients who may be safely
      discharged and determining whether further testing is needed remains challenging.
      From the prehospital care setting to disposition and follow-up, this systematic
      review addresses the fundamentals of the emergency department evaluation of
      patients determined to be at low risk for acute coronary syndromes or adverse
      outcomes. Clinical risk scores are discussed, as well as the evidence and
      indications for confirmatory testing. The emerging role of new technologies, such
      as high-sensitivity troponin assays and advanced imaging techniques, are also
      presented. [Points & Pearls is a digest of Emergency Medicine Practice].

PMID- 28742308
TI  - Nonaccidental injury in pediatric patients: detection, evaluation, and treatment
      [digest].
AB  - Emergency clinicians are likely to encounter physical abuse in children, and they
      must be prepared to recognize its many manifestations and take swift action.
      Pediatric nonaccidental injury causes considerable morbidity and mortality that
      can often be prevented by early recognition. Nonaccidental injuries present with
      a wide array of symptoms that may appear to be medically inconsequential (such as
      bruising in a premobile infant), but are actually sentinel injuries indicative of
      child abuse. This issue provides guidance regarding factors that contribute to
      abuse in children, key findings on history and physical examination that should
      trigger an evaluation for physical abuse, and laboratory and radiologic tests to
      perform when child abuse is suspected. [Points & Pearls is a digest of Pediatric
      Emergency Medicine Practice].

PMID- 28742309
TI  - Knowledge of rare diseases among health care students - the effect of targeted
      education
AB  - BACKGROUND: Poor knowledge on rare diseases (RD) results in a significant delay
      in their diagnosis and treatment. So far there are no standards of university
      education in RD. We assessed knowledge on RD among healthcare students and the
      effectiveness of targeted education. METHODS: We conducted an internet-based
      survey among students of the faculty of medicine, pharmacy and health sciences.
      Questions regarded personal information, definition and epidemic data on RD. The
      survey was used to assess the effect of targeted education about RD in an
      additional group of students. RESULTS: We enrolled 270 students (females: n=181;
      67%), aged 22+/-1.7 years. Most of them (87.8%) declared to be familiar with the
      term RD. However only 20.7% knew the correct definition of RD, 14% knew that RD
      affect a significant (6-8%) proportion of population, 21.4% that there are 5-8
      thousands of different RD' entities, 73.7% recognized the most common cause of
      RD. 12.6% knew, that the RD most frequently occur in the adulthood. Targeted
      education applied in the additional group of 18 students resulted in a
      significant improvement of students' knowledge on RD: definition (by 33%;
      p=0.007), percentage of population affected by RD (by 67%; p=0.001 ), total
      number of different RD (by 61%; p=0.003), time of onset of RD (by 61% p=0.003).
      CONCLUSIONS: Despite the declared recognition of the term: RD, knowledge on RD
      among medical students is poor independently on the year of study. However it can
      be improved with use of targeted education.

PMID- 28742310
TI  - Radon as a risk factor of lung cancer
AB  - Radon is the second leading cause of lung cancer after smoking. Indoor radon
      concentration poses a significant and potentially subject to the prevention risk
      factor of lung cancer development. The paper present the history of studies
      assessing occupational and indoor radon exposure and an impact of international
      organizations for raise public and political awareness about the consequences of
      long term exposure to residential radon, resulting in the European Directive
      2013/59/Euratom of 5 December 2013 laying down basic safety standards for
      protection against the dangers arising from exposure to ionising radiation.

PMID- 28742311
TI  - An analysis of selected risk factors of osteoporosis - dietary patterns and
      physical activity - in pubescent girls from the Lubelskie province
AB  - INTRODUCTION: Peak bone mass is modulated by intrinsic (genetic) and extrinsic
      factors, such as diet, physical activity, stimulants and medications.
      Approximately 80-85% of peak bone mass is achieved during puberty. OBJECTIVE: The
      aim of the study was to analyze selected risk factors for osteoporosis,
      specifically diet and physical activity, in 10- to 15-year-old girls. MATERIAL
      AND METHODS: The study included 461 girls from Eastern Poland (Lublin Province).
      Diet of the study subjects was determined with a 24-h dietary recall survey.
      Dietary intake of energy and selected nutrients was calculated using Dieta 5.0
      software. The analysis included intake of energy, protein, fat, calcium,
      phosphorus, magnesium, sodium, vitamins A, D and C. Physical activity of the
      study subjects was assessed by means of a diagnostic survey. Statistical analysis
      included determining mean dietary intakes of analyzed nutrients, as well as their
      deviations from the intakes recommended for a given age group (10-12 and 13-15
      years of age). Associations between diet and physical activity levels were tested
      with multivariate models of logistic regression, and their statistical
      significance was verified with Wald test. RESULTS: The study documented
      insufficient intake of energy, excessive intake of protein and sodium, as well as
      calcium, phosphorus and vitamin D deficiency. Most surveyed girls declared
      moderate level of physical activity. CONCLUSIONS: Dietary inadequacies observed
      in the studied girls may lead to inappropriate bone mineralization and as a
      result, contribute to development of osteoporosis in future. No evident
      relationships were found between diet and physical activity level.

PMID- 28742312
TI  - Health literacy and oral health literacy: are they associated? A cross sectional
      survey among undergraduate students of tricity (Chandigarh, Mohali, Panchkula),
      India
AB  - INTRODUCTION: Health Literacy is the degree to which individuals have the
      capacity to obtain, process, and understand basic health information and services
      needed to make appropriate decisions. As with general health; achieving and
      maintaining oral health requires one to be able to understand, interpret and act
      on various types of health information. OBJECTIVE: The present study was
      conducted to determine the association between health literacy and oral health
      literacy among undergraduate students in tricity (Chandigarh, Mohali, Panchkula),
      India. MATERIAL AND METHODS: A cross-sectional study was conducted among 490
      undergraduate students studying in tricity, from randomly selected 10 colleges.
      The data was collected by a single trained examiner, using a structured proforma.
      The questionnaire consisted of two parts, REALM-66 and REALD-30. The subject was
      given a copy of list of words to be pronounced and score one was given for each
      word pronounced correctly. RESULTS: REALM-66 scores showed that subjects with
      health literacy level equivalent to fourth- sixth grade is 1%, seventh- eighth
      grade was 64.4% and 29.6% for ninth grade and above. REALD-30 scores showed that
      37.6% subjects had low level of literacy, 33.1% had moderate and 29.3% had high
      level of literacy. REALM and REALD scores were found to be positively correlated
      for qualification and genders. CONCLUSIONS: To our knowledge, this is the first
      study reporting association between health and oral health literacy. As the
      correlations were not strong, thus the results should be regarded as a first step
      to provide evidence.

PMID- 28742313
TI  - The century of the studies on rabies in the National Institute of Hygiene in
      Warsaw

PMID- 28742314
TI  - The dysentery epidemic in Poland in 1920-1921
AB  - This article describes in general the issues related to the dysentery epidemic in
      1920-1921. The current literature on the subject lacks publications presenting
      these issues fully. Based on historical sources from that period, including
      articles published in medical magazines, the incidence rate, the methods and
      results of the battle against that epidemic were depicted. The article represents
      an important contribution to a better insight in the struggle of Polish medical
      services with infectious diseases afflicting people in the first years following
      the end of World War I. It also sheds light on the development of Polish studies
      on infectious diseases in the Second Polish Republic, the scientists' belief in
      the successful treatment of epidemic diseases and understanding of the need to
      educate people about the rules of hygiene and taking medicines.

PMID- 28742315
TI  - Wladyslaw Bieganski, MD (1857-1917)
AB  - Dr W. Bieganski was an eminent doctor of internal medicine mostly the acute
      infectious diseases and tuberculosis, he was scientist doing the research on the
      origin of the diseases and on the medical ethics, but more he was also a social
      activist taking care on the public health of the society in his time still living
      under the Russian rule. W. Bieganski living on the XIX/XX century in small
      provincial town, grace to his knowledge, self education and energy created the
      important scientific center in the municipal small hospital. His philosophic
      works and especially knowledge published under the shape of aphorisms on the
      medical ethics were several time published still after his death. The century of
      the death of Dr W. Bieganski the Senat of RP, the Higher Chamber of the Polish
      Parliament, celebrated by nominating him as one of the eminent persons for the
      year 2017. This publication was prepared to memorize the achievements of a
      medical doctor, scientists and social Dr W. Bieganski activists, that can be
      jugged as the precursor of the public health activist, and whose philosophical
      findings are still worth to be remember.

PMID- 28742316
TI  - Monodisperse Dual Plasmonic Au@Cu2-xE (E= S, Se) Core@Shell Supraparticles:
      Aqueous Fabrication, Multimodal Imaging, and Tumor Therapy at in Vivo Level.
AB  - We herein report aqueous fabrication of well-defined Au@Cu2-xE (E = S, Se)
      core@shell dual plasmonic supraparticles (SPs) for multimodal imaging and tumor
      therapy at the in vivo level. By means of a modified self-limiting self-assembly
      based strategy, monodisperse core@shell dual plasmonic SPs, including spherical
      Au@Cu2-xS SPs, Au@Cu2-xSe SPs, and rod-like Au@Cu2-xS SPs, are reliably and eco
      friendly fabricated in aqueous solution. Due to plasmonic coupling from the core
      and shell materials, the as-prepared hybrid products possess an extremely large
      extinction coefficient (9.32 L g-1 cm-1 for spherical Au@Cu2-xS SPs) at 808 nm,
      which endows their excellent photothermal effect. Furthermore, the hybrid
      core@shell SPs possess the properties of good biocompatibility, low nonspecific
      interactions, and high photothermal stability. So, they show favorable
      performances for photoacoustic imaging and X-ray computed tomography imaging as
      well as photothermal therapy of tumors, indicating their application potentials
      in biological field.

PMID- 28742317
TI  - Disposable Microfluidic Immunoarray Device for Sensitive Breast Cancer Biomarker
      Detection.
AB  - Breast cancer is the most common cancer in women worldwide. The detection of
      biomarkers has played a significant role in the early diagnosis and prognosis of
      breast cancer. Herein, we describe the construction of a disposable microfluidic
      immunoarray device (DMUID) for the rapid and low-cost detection of CA15-3
      (carbohydrate antigen 15-3), a protein biomarker for breast cancer. The DMUID was
      constructed using a simple and rapid prototyping technique and was applied to
      detect CA15-3 in cancer patients. The DMUID construction was based on the use of
      a double-sided adhesive card with a microfluidic channel and a screen-printed
      array with 8 electrodes. Both the immunoarray and microfluidic channel were
      designed using an inexpensive home cutter printer and using low-cost materials.
      The immunoarray was modified using the layer-by-layer technique aiming at
      immobilizing the primary antibody. For the biomarker detection, magnetic
      particles (MPs) modified with polyclonal antibodies and peroxidase enzymes were
      used as a strategy for capture, separation, and preconcentration of the
      biomarker, in addition to amplification of the electroanalytical signal. The
      preconcentration and amplification strategies integrated with the nanostructured
      immunosensors of the DMUID meaningfully contributed toward the detection of CA15
      3 with a limit of detection (LoD) of 6 MUU mL-1, requiring as low as 2 MUL of
      serum samples for 8 simultaneous detections. The obtained LoD was 1200 times
      lower compared to those of other immunosensors previously reported in the
      literature. The DMUID was applied for the detection of CA15-3 in real samples of
      breast cancer patients and was found to present an excellent correlation with the
      well-established commercial electrochemiluminescence immunoassay. The association
      of the DMUID with nanostructured surfaces and analyte capturing with
      bioconjugated paramagnetic particles is essentially a promising breakthrough for
      the low-cost and accurate detection of cancer biomarkers.

PMID- 28742318
TI  - Development of a Virtual Cell Model to Predict Cell Response to Substrate
      Topography.
AB  - Cells can sense and respond to changes in the topographical, chemical, and
      mechanical information in their environment. Engineered substrates are
      increasingly being developed that exploit these physical attributes to direct
      cell responses (most notably mesenchymal stem cells) and therefore control cell
      behavior toward desired applications. However, there are very few methods
      available for robust and accurate modeling that can predict cell behavior prior
      to experimental evaluations, and this typically means that many cell test
      iterations are needed to identify best material features. Here, we developed a
      unifying computational framework to create a multicomponent cell model, called
      the "virtual cell model" that has the capability to predict changes in whole cell
      and cell nucleus characteristics (in terms of shape, direction, and even
      chromatin conformation) on a range of cell substrates. Modeling data were
      correlated with cell culture experimental outcomes in order to confirm the
      applicability of the virtual cell model and demonstrating the ability to reflect
      the qualitative behavior of mesenchymal stem cells. This may provide a reliable,
      efficient, and fast high-throughput approach for the development of optimized
      substrates for a broad range of cellular applications including stem cell
      differentiation.

PMID- 28742319
TI  - Petal-like MoS2 Nanosheets Space-Confined in Hollow Mesoporous Carbon Spheres for
      Enhanced Lithium Storage Performance.
AB  - An innovative approach for efficient synthesis of petal-like molybdenum disulfide
      nanosheets inside hollow mesoporous carbon spheres (HMCSs), the yolk-shell
      structured MoS2@C, has been developed. HMCSs effectively control and confine in
      situ growth of MoS2 nanosheets and significantly improve the conductivity and
      structural stability of the hybrid material. The yolk-shell structured MoS2@C is
      proven to achieve high reversible capacity (993 mA h g-1 at 1 A g-1 after 200
      cycles), superior rate capability (595 mA h g-1 at a current density of 10 A g
      1), and excellent cycle performance (962 mA h g-1 at 1 A g-1 after 1000 cycles
      and 624 mA h g-1 at 5 A g-1 after 400 cycles) when evaluated as an anode material
      for lithium-ion batteries. This superior performance is attributed to the yolk
      shell structure with conductive mesoporous carbon as the shell and the stack of
      two-dimensional MoS2 nanosheets as the yolk.

PMID- 28742320
TI  - Nanoscale Probing of Elastic-Electronic Response to Vacancy Motion in NiO
      Nanocrystals.
AB  - Measuring the diffusion of ions and vacancies at nanometer length scales is
      crucial to understanding fundamental mechanisms driving technologies as diverse
      as batteries, fuel cells, and memristors; yet such measurements remain extremely
      challenging. Here, we employ a multimodal scanning probe microscopy (SPM)
      technique to explore the interplay between electronic, elastic, and ionic
      processes via first-order reversal curve I-V measurements in conjunction with
      electrochemical strain microscopy (ESM). The technique is employed to investigate
      the diffusion of oxygen vacancies in model epitaxial nickel oxide (NiO)
      nanocrystals with resistive switching characteristics. Results indicate that
      opening of the ESM hysteresis loop is strongly correlated with changes to the
      resonant frequency, hinting that elastic changes stem from the motion of oxygen
      (or cation) vacancies in the probed volume of the SPM tip. These changes are
      further correlated to the current measured on each nanostructure, which shows a
      hysteresis loop opening at larger (~2.5 V) voltage windows, suggesting the
      threshold field for vacancy migration. This study highlights the utility of local
      multimodal SPM in determining functional and chemical changes in nanoscale
      volumes in nanostructured NiO, with potential use to explore a wide variety of
      materials including phase-change memories and memristive devices in combination
      with site-correlated chemical imaging tools.

PMID- 28742321
TI  - Understanding the Effect of Functional Groups on the Seeded Growth of Copper on
      Carbon Nanotubes for Optimizing Electrical Transmission.
AB  - We present a study of the seeded growth of copper on the surface of two classes
      of single-walled carbon nanotubes (SWNTs) in order to compare the effects of
      surface functional groups. Pyridine-functionalized HiPco SWNTs and ultrashort
      SWNTs (US-SWNTs) were synthesized (py-SWNTs and py-US-SWNTs, respectively), and
      the functionality was used as seed sites for copper, via an aqueous electroless
      deposition reaction, as a comparison to the carboxylic acid functionality present
      on piranha-etched SWNTs and the native US-SWNTs. UV-vis spectroscopy demonstrated
      the take-up of Cu(II) ions by the functionalized SWNTs. TEM showed that the SWNTs
      with pyridine functionality more rapidly produced a more even distribution of
      copper seeds with a narrower size distribution (3-12 nm for py-US-SWNTs) than
      those SWNTs with oxygen functional groups (ca. 30 nm), showing the adventitious
      role of the pyridine functional group in the seeding process. Seed composition
      was confirmed as Cu(0) by XPS and SAED. Copper growth rate and morphology were
      shown to be affected by degree of pyridine functionality, the length of the SWNT,
      and the electroless reaction solvent used.

PMID- 28742322
TI  - Modeling Mechanochemical Reaction Mechanisms.
AB  - The mechanochemical reaction between copper and dimethyl disulfide is studied
      under well-controlled conditions in ultrahigh vacuum (UHV). Reaction is initiated
      by fast S-S bond scission to form adsorbed methyl thiolate species, and the
      reaction kinetics are reproduced by two subsequent elementary mechanochemical
      reaction steps, namely a mechanochemical decomposition of methyl thiolate to
      deposit sulfur on the surface and evolve small, gas-phase hydrocarbons, and
      sliding-induced oxidation of the copper by sulfur that regenerates vacant
      reaction sites. The steady-state reaction kinetics are monitored in situ from the
      variation in the friction force as the reaction proceeds and modeled using the
      elementary-step reaction rate constants found for monolayer adsorbates. The
      analysis yields excellent agreement between the experiment and the kinetic model,
      as well as correctly predicting the total amount of subsurface sulfur in the film
      measured using Auger spectroscopy and the sulfur depth distribution measured by
      angle-resolved X-ray photoelectron spectroscopy.

PMID- 28742323
TI  - Response Characteristics of Hydrogen Sensors Based on PMMA-Membrane-Coated
      Palladium Nanoparticle Films.
AB  - Coating a polymeric membrane for gas separation is a feasible approach to
      fabricate gas sensors with selectivity. In this study, poly(methyl methacrylate)
      (PMMA-)membrane-coated palladium (Pd) nanoparticle (NP) films were fabricated for
      high-performance hydrogen (H2) gas sensing by carrying out gas-phase cluster
      deposition and PMMA spin coating. No changes were induced by the PMMA spin
      coating in the electrical transport and H2-sensing mechanisms of the Pd NP films.
      Measurements of H2 sensing demonstrated that the devices were capable of
      detecting H2 gas within the concentration range 0-10% at room temperature and
      showed high selectivity to H2 due to the filtration effect of the PMMA membrane
      layer. Despite the presence of the PMMA matrix, the lower detection limit of the
      sensor is less than 50 ppm. A series of PMMA membrane layers with different
      thicknesses were spin coated onto the surface of Pd NP films for the selective
      filtration of H2. It was found that the device sensing kinetics were strongly
      affected by the thickness of the PMMA layer, with the devices with thicker PMMA
      membrane layers showing a slower response to H2 gas. Three mechanisms slowing
      down the sensing kinetics of the devices were demonstrated to be present:
      diffusion of H2 gas in the PMMA matrix, nucleation and growth of the beta phase
      in the alpha phase matrix of Pd hydride, and stress relaxation at the interface
      between Pd NPs and the PMMA matrix. The retardation effect caused by these three
      mechanisms on the sensing kinetics relied on the phase region of Pd hydride
      during the sensing reaction. Two simple strategies, minimizing the thickness of
      the PMMA membrane layer and reducing the size of the Pd NPs, were proposed to
      compensate for retardation of the sensing response.

PMID- 28742324
TI  - Simple Microwave-Assisted Synthesis of Amphiphilic Carbon Quantum Dots from A3/B2
      Polyamidation Monomer Set.
AB  - Highly fluorescent and amphiphilic carbon quantum dots (CQDs) were prepared by
      microwave-assisted pyrolysis of citric acid and 4,7,10-trioxa-1,13
      tridecanediamine (TTDDA), which functioned as an A3 and B2 polyamidation type
      monomer set. Gram quantities of fluorescent CQDs were easily obtained within 5
      min of microwave heating using a household microwave oven. Because of the dual
      role of TTDDA, both as a constituting monomer and as a surface passivation agent,
      TTDDA-based CQDs showed a high fluorescence quantum yield of 29% and amphiphilic
      solubility in various polar and nonpolar solvents. These properties enable the
      wide application of TTDDA-based CQDs as nontoxic bioimaging agents, nanofillers
      for polymer composites, and down-converting layers for enhancing the efficiency
      of Si solar cells.

PMID- 28742325
TI  - Intentional Closing/Opening of "Hole-in-Cube" Fullerene Crystals with Microscopic
      Recognition Properties.
AB  - We report production of highly crystalline fullerene C70 cubes possessing an open
      hole structure at the center of each of their faces using a solution-based self
      assembly strategy. The holes are isolated with a solid core at the interiors of
      the cubes. The open-hole structure of the cubes can be intentionally closed by
      introducing additional C70 and reopened by applying electron beam irradiation.
      The open-hole cubes exhibit preferential recognition of graphitic carbon
      particles over polymeric resin particles of similar dimensions due to the cubes'
      sp2-rich carboniferous nature.

PMID- 28742326
TI  - Tellurium-Impregnated Porous Cobalt-Doped Carbon Polyhedra as Superior Cathodes
      for Lithium-Tellurium Batteries.
AB  - Lithium-tellurium (Li-Te) batteries are attractive for energy storage owing to
      their high theoretical volumetric capacity of 2621 mAh cm-3. In this work, highly
      nanoporous cobalt and nitrogen codoped carbon polyhedra (C-Co-N) derived from a
      metal-organic framework (MOF) is synthesized and employed as tellurium host for
      Li-Te batteries. The Te@C-Co-N cathode with a high Te loading of 77.2 wt %
      exhibits record-breaking electrochemical performances including an ultrahigh
      initial capacity of 2615.2 mAh cm-3 approaching the theoretical capacity of Te
      (2621 mAh cm-3), a superior cycling stability with a high capacity retention of
      93.6%, a ~99% Columbic efficiency after 800 cycles as well as rate capacities of
      2160, 1327.6, and 894.8 mAh cm-3 at 4, 10, and 20 C, respectively. The redox
      chemistry of tellurium is revealed by in operando Raman spectroscopic analysis
      and density functional theory simulations. The results illustrate that the
      performances are attributed to the highly conductive C-Co-N matrix with an
      advantageous structure of abundant micropores, which provides highly efficient
      channels for electron transfer and ionic diffusion as well as sufficient surface
      area to efficiently host tellurium while mitigating polytelluride dissolution and
      suppressing volume expansion.

PMID- 28742327
TI  - Amphiphilic Peptide Nanorods Based on Oligo-Phenylalanine as a Biocompatible Drug
      Carrier.
AB  - Peptide nanostructure has been widely explored for drug-delivery systems in
      recent studies. Peptides possess comparatively lower cytotoxicity and are more
      efficient than polymeric carriers. Here, we propose a peptide nanorod system,
      composed of an amphiphilic oligo-peptide RH3F8 (Arg-His3-Phe8), as a drug
      delivery carrier. Arginine is an essential amino acid in typical cell-penetration
      peptides, and histidine induces endo- and lysosomal escape because of its proton
      sponge effect. Phenylalanine is introduced to provide rich hydrophobicity for
      stable self-assembly and drug encapsulation. The self-assembled structure of
      RH3F8 showed nanorod-shaped morphology, positive surface charge, and retained
      formation in water for 35 days. RH3F8, labeled with Nile Red, showed high cellar
      uptake and accumulation in both cytoplasm and nucleus. The RH3F8 nanorods
      demonstrated negligible cytotoxicity, as shown by the 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and
      hemolysis assays. To confirm the efficiency of drug delivery, curcumin was
      encapsulated in the RH3F8 nanorod system (RH3F8-Cur). RH3F8-Cur showed high
      encapsulation efficiency (24.63%) under the conditions of 200 MUM curcumin. The
      RH3F8-Cur retained nanoscale size and positive surface charge, similar to those
      of the empty RH3F8 nanorods. RH3F8-Cur displayed a robust anticancer effect in
      HeLa and A549 cells, and inhibited the proliferation of cancer cells in a
      zebrafish model. These results indicate that the RH3F8 nanorods may be a
      promising candidate for a safe and effective drug-delivery system.

PMID- 28742328
TI  - Attachable Pulse Sensors Integrated with Inorganic Optoelectronic Devices for
      Monitoring Heart Rates at Various Body Locations.
AB  - Monitoring cardiovascular signals such as heart rate and blood flow provides
      critically important healthcare information about patients under medical care.
      However, when the sensors are worn for extended times, the sensors sometimes
      require higher mechanical compatibility with soft deformable tissues. In this
      paper, we report an attachable and flexible pulse sensor (bending radius: 2.4
      mm), integrated with micro-inorganic photodetectors (thickness: 4.1 MUm,
      photocurrent: 8.99 MUA under 1.5 mW/cm2) and a red light emitting diode (620 nm),
      to monitor vital signals for extended times. Operating in a reflection mode, it
      can be attached and measure heart pulse waveforms from various locations on the
      human body including the finger, fingertip, nail, and forearm. The small form
      factor also enables integration on a finger ring. Electrical and mechanical
      performance assessments demonstrated the practical feasibility of the concept.

PMID- 28742329
TI  - Selecting a DNA-Encoded Chemical Library against Non-immobilized Proteins Using a
      "Ligate-Cross-Link-Purify" Strategy.
AB  - DNA-encoded chemical libraries (DELs) have recently emerged and become an
      important technology platform in biomedical research and drug discovery. DELs
      containing large numbers of compounds can be prepared and selected against
      biological targets to discover novel ligands and inhibitors. In practice, DELs
      are usually selected against purified and immobilized proteins using the typical
      "bind-wash-elute" protocol; however, selection methods compatible with non
      immobilized proteins would be able to greatly expand the target scope of DELs
      beyond purified proteins to more-complex and biologically relevant targets. Using
      a novel "ligate-cross-link-purify" strategy, we report here a method capable of
      selecting DELs against unmodified and non-immobilized protein targets. In
      addition, this method has shown excellent capability in identifying binders with
      moderate and weak affinities.

PMID- 28742330
TI  - Computational Screening of Bimetal-Functionalized Zr6O8 MOF Nodes for Methane C-H
      Bond Activation.
AB  - Zr-based metal-organic frameworks (MOFs) are promising supports for copper-based
      catalysts able to activate methane. Homo- and heterobimetal-functionalized NU
      1000 MOF nodes were selected to computationally screen the effect of ancillary
      metals for C-H bond activation, allowing us to correlate activation free energies
      with chemical descriptors.

PMID- 28742331
TI  - Deep-Ultraviolet Nonlinear-Optical Material K3Sr3Li2Al4B6O20F: Addressing the
      Structural Instability Problem in KBe2BO3F2.
AB  - A beryllium-free deep-ultraviolet (DUV) nonlinear-optical (NLO) material,
      K3Sr3Al4Li2B6O20F, has been synthesized and characterized. Unlike KBe2BO3F2
      (KBBF), the reported NLO material does not require the use of toxic BeO in the
      synthesis, and through the judicious selection of cations, strong interlayer
      interactions are observed that facilitate the crystal growth. K3Sr3Al4Li2B6O20F
      exhibits second-harmonic generation (SHG) at both 1064 and 532 nm with
      efficiencies of 1.7KH2PO4 and 0.3beta-BaB2O4 and has an absorption edge of 190
      nm. Because of the strong interlayer interactions, we were able to grow well
      faceted large crystals, 8 * 8 * 5 mm3, through a top-seeded-solution-growth
      technique. With these crystals, we determined a birefringence of 0.0574 at 1064
      nm and a type I phase-matching SHG limit of 224 nm.

PMID- 28742332
TI  - Modulation of Lipid Digestion Profiles Using Filled Egg White Protein Microgels.
AB  - Colloidal delivery systems are required to encapsulate, protect, and release
      active food ingredients, such as vitamins, nutraceuticals, and minerals. In this
      study, lipid droplets were encapsulated within biopolymer microgels fabricated
      from egg white proteins using an injection-gelation process. Confocal
      fluorescence microscopy indicated that lipid droplets were dispersed within a
      network of cross-linked proteins within the microgels. The properties of the
      lipid-loaded microgels were compared to those of simple oil-in-water emulsions
      stabilized by egg white proteins. Light scattering and microscopy measurements
      indicated that both delivery systems exhibited good stability under acid
      conditions (pH 3-5) but aggregated at higher pH values as a result of a reduction
      in electrostatic repulsion. Simulated gastrointestinal tract studies indicated
      that lipid droplets encapsulated within protein microgels were digested more
      slowly than free lipid droplets. Our results therefore suggest that egg white
      protein microgels may be useful for encapsulation and controlled release of
      hydrophobic bioactive agents.

PMID- 28742333
TI  - Alkyne Hydroheteroarylation: Enantioselective Coupling of Indoles and Alkynes via
      Rh-Hydride Catalysis.
AB  - We report an enantioselective coupling between alkynes and indoles. A Rh-hydride
      catalyst isomerizes alkynes to generate a metal-allyl species that can be trapped
      with both aromatic and heteroaromatic nucleophiles.

PMID- 28742334
TI  - Health Effects of Dietary Oxidized Tyrosine and Dityrosine Administration in Mice
      with Nutrimetabolomic Strategies.
AB  - This study aims to investigate the health effects of long-term dietary oxidized
      tyrosine (O-Tyr) and its main product (dityrosine) administration on mice
      metabolism. Mice received daily intragastric administration of either O-Tyr (320
      MUg/kg body weight), dityrosine (Dityr, 320 MUg/kg body weight), or saline for
      consecutive 6 weeks. Urine and plasma samples were analyzed by NMR-based
      metabolomics strategies. Body weight, clinical chemistry, oxidative damage
      indexes, and histopathological data were obtained as complementary information. O
      Tyr and Dityr exposure changed many systemic metabolic processes, including
      reduced choline bioavailability, led to fat accumulation in liver, induced
      hepatic injury, and renal dysfunction, resulted in changes in gut microbiota
      functions, elevated risk factor for cardiovascular disease, altered amino acid
      metabolism, induced oxidative stress responses, and inhibited energy metabolism.
      These findings implied that it is absolutely essential to reduce the generation
      of oxidation protein products in food system through improving modern food
      processing methods.

PMID- 28742335
TI  - 5-Formylcytosine Yields DNA-Protein Cross-Links in Nucleosome Core Particles.
AB  - In situ generation of 5-formylcytosine (5fC) in nucleosome core particles (NCPs)
      reveals that 5fC leads to essential DNA-protein cross-links (DPCs). Mechanistic
      studies using chemical models and mutated histones demonstrate that DPCs form
      reversibly between the formyl function of 5fC and primary amines on histones.
      These results suggest that DPC formation from 5fC in chromatin occurs in addition
      to its role in DNA demethylation.

PMID- 28742336
TI  - Quantum Chemically Estimated Abraham Solute Parameters Using Multiple Solvent
      Water Partition Coefficients and Molecular Polarizability.
AB  - Polyparameter Linear Free Energy Relationships (pp-LFERs), also called Linear
      Solvation Energy Relationships (LSERs), are used to predict many environmentally
      significant properties of chemicals. A method is presented for computing the
      necessary chemical parameters, the Abraham parameters (AP), used by many pp
      LFERs. It employs quantum chemical calculations and uses only the chemical's
      molecular structure. The method computes the Abraham E parameter using density
      functional theory computed molecular polarizability and the Clausius-Mossotti
      equation relating the index refraction to the molecular polarizability, estimates
      the Abraham V as the COSMO calculated molecular volume, and computes the
      remaining AP S, A, and B jointly with a multiple linear regression using sixty
      five solvent-water partition coefficients computed using the quantum mechanical
      COSMO-SAC solvation model. These solute parameters, referred to as Quantum
      Chemically estimated Abraham Parameters (QCAP), are further adjusted by fitting
      to experimentally based APs using QCAP parameters as the independent variables so
      that they are compatible with existing Abraham pp-LFERs. QCAP and adjusted QCAP
      for 1827 neutral chemicals are included. For 24 solvent-water systems including
      octanol-water, predicted log solvent-water partition coefficients using adjusted
      QCAP have the smallest root-mean-square errors (RMSEs, 0.314-0.602) compared to
      predictions made using APs estimated using the molecular fragment based method
      ABSOLV (0.45-0.716). For munition and munition-like compounds, adjusted QCAP has
      much lower RMSE (0.860) than does ABSOLV (4.45) which essentially fails for these
      compounds.

PMID- 28742337
TI  - Gallium Complexation, Stability, and Bioconjugation of 1,4,7-Triazacyclononane
      Derived Chelators with Azaheterocyclic Arms.
AB  - We have recently introduced a 1,4,7-triazacyclononane (TACN) based chelating
      system with additional five-membered azaheterocyclic substituents for
      complexation of radioactive Cu2+ ions. In this work, we investigated the
      complexation properties of these novel chelators with Ga3+. In labeling
      experiments, we could show that the penta- and hexadentate imidazole derivatives
      NODIA-Me 4 and NOTI-Me 1 can be labeled with 68Ga in specific activities up to
      ~30 MBq nmol-1, while the corresponding thiazole derivative NOTThia 2 did not
      label satisfactorily under identical conditions. NMR studies on the Ga complexes
      of 1 and the model compound NODIA-Me-NH-Me 5 revealed formation of rigid 1:1
      chelates with a slow macrocyclic interconversion and inert Ga-N bonds to the
      methylimidazole residues on the NMR time scale. The TACN-derived bifunctional
      chelator NODIA-Me was furthermore conjugated to a prostate-specific membrane
      antigen (PSMA) targeting moiety to give the corresponding bioconjugate NODIA-Me
      PSMA 7. Serum stability and ligand challenge experiments of 68Ga-7 confirmed
      formation of a stable complex for up to 4 h. The remaining coordination site of
      five-coordinate Ga complexes was found to be occupied by monodentate ligands
      including hydroxide and chloride anions depending on the conditions. According to
      density functional theory calculations, coordination of monodentate ligands as
      well as of the amide group for the bioconjugated ligand are energetically
      plausible. Finally, the labeled bioconjugate 68Ga-7 exhibited rapid renal
      clearance in biodistribution studies performed by small animal PET imaging with
      no indication of transchelation/demetalation in vivo. Altogether, our results
      provide strong evidence for a stable Ga complexation of our novel TACN-based
      chelators bearing imidazole arms. Despite the formation of two complexes
      incorporating different monodentate ligands in vitro, the imidazole type ligands
      show promise as chelating agents for the future development of gallium based
      radiopharmaceuticals.

PMID- 28742338
TI  - Advanced Materials, Technologies, and Complex Systems Analyses: Emerging
      Opportunities to Enhance Urban Water Security.
AB  - Innovation in urban water systems is required to address the increasing demand
      for clean water due to population growth and aggravated water stress caused by
      water pollution, aging infrastructure, and climate change. Advances in materials
      science, modular water treatment technologies, and complex systems analyses,
      coupled with the drive to minimize the energy and environmental footprints of
      cities, provide new opportunities to ensure a resilient and safe water supply. We
      present a vision for enhancing efficiency and resiliency of urban water systems
      and discuss approaches and research needs for overcoming associated
      implementation challenges.

PMID- 28742339
TI  - VMS-ROT: A New Module of the Virtual Multifrequency Spectrometer for Simulation,
      Interpretation, and Fitting of Rotational Spectra.
AB  - The Virtual Multifrequency Spectrometer (VMS) is a tool that aims at integrating
      a wide range of computational and experimental spectroscopic techniques with the
      final goal of disclosing the static and dynamic physical-chemical properties
      "hidden" in molecular spectra. VMS is composed of two parts, namely, VMS-Comp,
      which provides access to the latest developments in the field of computational
      spectroscopy, and VMS-Draw, which provides a powerful graphical user interface
      (GUI) for an intuitive interpretation of theoretical outcomes and a direct
      comparison to experiment. In the present work, we introduce VMS-ROT, a new module
      of VMS that has been specifically designed to deal with rotational spectroscopy.
      This module offers an integrated environment for the analysis of rotational
      spectra: from the assignment of spectral transitions to the refinement of
      spectroscopic parameters and the simulation of the spectrum. While bridging
      theoretical and experimental rotational spectroscopy, VMS-ROT is strongly
      integrated with quantum-chemical calculations, and it is composed of four
      independent, yet interacting units: (1) the computational engine for the
      calculation of the spectroscopic parameters that are employed as a starting point
      for guiding experiments and for the spectral interpretation, (2) the fitting
      prediction engine for the refinement of the molecular parameters on the basis of
      the assigned transitions and the prediction of the rotational spectrum of the
      target molecule, (3) the GUI module that offers a powerful set of tools for a vis
      a-vis comparison between experimental and simulated spectra, and (4) the new
      assignment tool for the assignment of experimental transitions in terms of
      quantum numbers upon comparison with the simulated ones. The implementation and
      the main features of VMS-ROT are presented, and the software is validated by
      means of selected test cases ranging from isolated molecules of different sizes
      to molecular complexes. VMS-ROT therefore offers an integrated environment for
      the analysis of the rotational spectra, with the innovative perspective of an
      intimate connection to quantum-chemical calculations that can be exploited at
      different levels of refinement, as an invaluable support and complement for
      experimental studies.

PMID- 28742340
TI  - Structure and Electrical-Transport Relations in Ba(Zr,Pr)O3-delta Perovskites.
AB  - Members of the perovskite solid solution BaZr1-xPrxO3-delta (0.2 <= x <= 0.8)
      with potential high-temperature electrochemical applications were synthesized via
      mechanical activation and high-temperature annealing at 1250  degrees C.
      Structural properties were examined by Rietveld analysis of neutron powder
      diffraction and Raman spectroscopy at room temperature, indicating rhombohedral
      symmetry (space group R3c) for members x = 0.2 and 0.4 and orthorhombic symmetry
      (Imma) for x = 0.6 and 0.8. The sequence of phase transitions for the complete
      solid solution from BaZrO3 to BaPrO3 is Pm3m -> R3c -> Imma -> Pnma. The
      structural data indicate that Pr principally exists as Pr4+ on the B site and
      that oxygen content increases with higher Pr content. Electrical-conductivity
      measurements in the temperature range of 250-900  degrees C in dry and humidified
      (pH2O ~ 0.03 atm) N2 and O2 atmospheres revealed an increase of total
      conductivity by over 2 orders of magnitude in dry conditions from x = 0.2 to x =
      0.8 (sigma ~ 0.08 S cm-1 at 920  degrees C in dry O2 for x = 0.8). The
      conductivity for Pr contents x > 0.2 is attributable to positively charged
      electronic carriers, whereas for x = 0.2 transport in dry conditions is n-type.
      The change in conduction mechanism with composition is proposed to arise from the
      compensation regime for minor amounts of BaO loss changing from predominantly
      partitioning of Pr on the A site to vacancy formation with increasing Pr content.
      Conductivity is lower in wet conditions for x > 0.2 indicating that the positive
      defects are, to a large extent, charge compensated by less mobile protonic
      species. In contrast, the transport mechanism of the Zr-rich composition (x =
      0.2), with much lower electronic conductivity, is essentially independent of
      moisture content.

PMID- 28742341
TI  - Synthesis Strategies to Extend the Variety of Alginate-Based Hybrid Hydrogels for
      Cell Microencapsulation.
AB  - The production of hydrogel microspheres (MS) for cell immobilization, maintaining
      the favorable properties of alginate gels but presenting enhanced performance in
      terms of in vivo durability and physical properties, is desirable to extend the
      therapeutic potential of cell transplantation. A novel type of hydrogel MS was
      produced by straightforward functionalization of sodium alginate (Na-alg) with
      heterotelechelic poly(ethylene glycol) (PEG) derivatives equipped with either end
      thiol or 1,2-dithiolane moieties. Activation of the hydroxyl moieties of the
      alginate backbone in the form of imidazolide intermediate allowed for fast
      conjugation to PEG oligomers through a covalent carbamate linkage. Evaluation of
      the modified alginates for the preparation of MS combining fast ionic gelation
      ability of the alginate carboxylate groups and slow covalent cross-linking
      provided by the PEG-end functionalities highlighted the influence of the chemical
      composition of the PEG-grafting units on the physical characteristics of the MS.
      The mechanical properties of the MS (resistance and shape recovery) and
      durability of PEG-grafted alginates in physiological environment can be adjusted
      by varying the nature of the end functionalities and the length of the PEG
      chains. In vitro cell microencapsulation studies and preliminary in vivo
      assessment suggested the potential of these hydrogels for cell transplantation
      applications.

PMID- 28742342
TI  - The Structure of Thymidylate Kinase from Candida albicans Reveals a Unique
      Structural Element.
AB  - The structure of thymidylate kinase from Candida albicans, determined by X-ray
      crystallography, is reported to a resolution of 2.45 A with a final Rfree of
      0.223. Thymidylate kinase from C. albicans possesses a unique 15-residue loop
      that is not seen in thymidylate kinases from other genera. The structure reported
      here reveals that the conformation of this loop is constrained by both intra- and
      intersubunit hydrogen bonding, and a number of key residues in this loop are
      conserved among different Candida species that are medically important. The
      substrate specificity of the enzyme was determined using a novel nuclear magnetic
      resonance-based assay as well as a traditional coupled assay. The enzyme is
      active against 3'-azido-3'-deoxythymidine monophosphate and moderately active
      with dGMP. The distinct functional and structural differences between the C.
      albicans enzyme and the human enzyme suggest that thymidylate kinase is an
      appropriate target for the development of new antifungal agents.

PMID- 28742343
TI  - Stability of Sodium Chlorate Residues in Frozen Tomato and Cantaloupe
      Homogenates.
AB  - The objective of this study was to determine the stability of sodium chlorate in
      frozen (-24  degrees C) tomato or cantaloupe homogenates for up to 17 weeks (119
      days). Chlorate stability was assessed by ultraperformance liquid chromatography
      mass spectrometry (UPLC-MS/MS) at two fortification levels (80 or 600 ng/g for
      tomato and 200 or 3000 ng/g for cantaloupe, n = 3 each) for each fruit after
      storage for 0, 1, 7, 14, 28, 56, or 119 d. Within matrix type, chlorate recovery
      was determined by fortifying duplicate blank homogenate samples on the day of
      analysis with the same concentrations used for the stability samples. Chlorate
      limits of quantitation for cantaloupe and tomato matrices were 30 and 60 ng/g,
      respectively. Sodium chlorate residues were stable (P > 0.05) in frozen tomato
      and cantaloupe homogenates during storage for 119 days at -24  degrees C.

PMID- 28742344
TI  - Insights into the Molybdenum/Copper Heterometallic Cluster Assembly in the Orange
      Protein: Probing Intermolecular Interactions with an Artificial Metal-Binding
      ATCUN Tag.
AB  - Orange protein (ORP) is a small bacterial protein, of unknown function, that
      contains a unique molybdenum/copper heterometallic cluster,
      [S2MoVIS2CuIS2MoVIS2]3- (Mo/Cu), non-covalently bound. The native cluster can be
      reconstituted in a protein-assisted mode by the addition of CuII plus
      tetrathiomolybdate to apo-ORP under controlled conditions. In the work described
      herein, we artificially inserted the ATCUN ("amino terminus Cu and Ni") motif in
      the Desulfovibrio gigas ORP (Ala1Ser2His3 followed by the native amino acid
      residues; modified protein abbreviated as ORP*) to increase our understanding of
      the Mo/Cu cluster assembly in ORP. The apo-ORP* binds CuII in a 1:1 ratio to
      yield CuII-ORP*, as clearly demonstrated by EPR (g||,? = 2.183, 2.042 and ACu||,?
      = 207 * 10-4 cm-1, 19 * 10-4 cm-1) and UV-visible spectroscopies (typical d-d
      transition bands at 520 nm, epsilon = 90 M-1 cm-1). The 1H NMR spectrum shows
      that His3 and His53 are significantly affected upon the addition of the CuII. The
      X-ray structure shows that these two residues are very far apart (Calpha-Calpha ~
      27.9 A), leading us to suggest that the metal-induced NMR perturbations are due
      to the interaction of two protein molecules with a single metal ion. Docking
      analysis supports the metal-mediated dimer formation. The subsequent
      tetrathiomolybdate binding, to yield the native Mo/Cu cluster, occurs only upon
      addition of dithiothreitol, as shown by UV-visible and NMR spectroscopies.
      Additionally, 1H NMR of AgI-ORP* (AgI used as a surrogate of CuI) showed that AgI
      strongly binds to a native methionine sulfur atom rather than to the ATCUN site,
      suggesting that CuII and CuI have two different binding sites in ORP*. A detailed
      mechanism for the formation of the Mo/Cu cluster is discussed, suggesting that
      CuII is reduced to CuI and transferred from the ATCUN motif to the methionine
      site; finally, CuI is transferred to the cluster-binding region, upon the
      interaction of two protein molecules. This result may suggest that copper
      trafficking is triggered by redox-dependent coordination properties of copper in
      a trafficking pathway.

PMID- 28742345
TI  - Syntheses, Structures, and Comparisons of Heterometallic Uranyl Iodobenzoates
      with Monovalent Cations.
AB  - The syntheses and crystal structures of six new heterometallic compounds
      containing the UO22+ cation, o-, m-, and p-iodobenzoic acid ligands, and Tl+,
      Rb+, and Cs+ cations which adopt the role of both charge balancing cation and
      secondary metal center are described, as are the luminescent properties for Tl+
      containing compounds 1, 4, and 6. The structures of compounds 1-3 are isomorphous
      and contain uranyl monomers bound by o-iodobenzoic acid ligands with Tl+, Rb+,
      and Cs+ cations acting as secondary metal centers. Compounds 4 and 5 are also
      isomorphous and feature m-iodobenzoic acid ligands bound to the uranyl cation
      along with Tl+ and Rb+ cations. Compound 6 is unique in this series as it is
      assembled from a dimeric uranyl unit and features p-iodobenzoic acid ligands and
      Tl+ cations which function as charge balancing secondary metal centers. Single
      crystal X-ray diffraction analysis of these materials suggests that the secondary
      metal cations are incorporated based on the size of their ionic radius (Tl+ < Rb+
      < Cs+), which is directly related to the size of the "pocket" observed in 1-6.
      Further, Voronoi-Dirichlet tessellation and Hirshfeld surface analysis were used
      to probe the coordination environment of the secondary metal centers as part of
      ongoing efforts to develop metrics for determining the coordination number of
      secondary metal cations in similar systems.

PMID- 28742346
TI  - Molecular Dynamics of Double Stranded Xylo-Nucleic Acid.
AB  - Xylo-nucleic acid (XyloNA) is a synthetic analogue of ribo-nucleic acid (RNA),
      where the ribose sugar has been replaced by xylose. We present a molecular
      dynamics study of the conformational evolution of XyloNA double strand oligomers
      derived from A-RNA through the substitution of beta-d-ribofuranose by beta-d
      xylofuranose and having lengths of 8, 16, and 29 base pairs, using a set of
      independent all-atom simulations performed at various time scales ranging from 55
      to 100 ns, with one long 500 ns simulation of the 29-mer. In order to validate
      the robustness of XyloNA conformation, a set of simulations using various cutoff
      distances and solvation box dimensions has also been performed. These independent
      simulations reveal the uncoiling or elongation of the initial conformation to
      form an open ladder type transient state conformation and the subsequent
      formation of a highly flexible duplex with a tendency to coil in a left-handed
      fashion. The observed open ladder conformation is in line with recently obtained
      NMR data on the XyloNA 8-mer derived using 5'-d(GUGUACAC)-3'. The observed
      negative interbase pair twist leads to the observed highly flexible left-handed
      duplex, which is significantly less rigid than the stable left-handed dXyloNA
      duplex having a strong negative twist. A comparison between the xylo-analogues of
      DNA and RNA shows a clear distinction between the helical parameters, with
      implications for the pairing mechanism.

PMID- 28742347
TI  - Cationic and Anionic Impact on the Electronic Structure of Liquid Water.
AB  - Hydration shells around ions are crucial for many fundamental biological and
      chemical processes. Their local physicochemical properties are quite different
      from those of bulk water and hard to probe experimentally. We address this
      problem by combining soft X-ray spectroscopy using a liquid jet and molecular
      dynamics (MD) simulations together with ab initio electronic structure
      calculations to elucidate the water-ion interaction in a MgCl2 solution at the
      molecular level. Our results reveal that salt ions mainly affect the electronic
      properties of water molecules in close vicinity and that the oxygen K-edge X-ray
      emission spectrum of water molecules in the first solvation shell differs
      significantly from that of bulk water. Ion-specific effects are identified by
      fingerprint features in the water X-ray emission spectra. While Mg2+ ions cause a
      bathochromic shift of the water lone pair orbital, the 3p orbital of the Cl- ions
      causes an additional peak in the water emission spectrum at around 528 eV.

PMID- 28742348
TI  - Observation of Structural Wavepacket Motion: The Umbrella Mode in Rydberg-Excited
      N-Methyl Morpholine.
AB  - We have observed time-resolved, structural dynamics of a coherent vibrational
      wavepacket in Rydberg-excited N-methyl morpholine, a molecule with 48 internal
      degrees of freedom. The molecular structure was established by associating the
      time-dependent Rydberg electron binding energy, obtained from time-resolved
      photoionization-photoelectron spectroscopy, to the molecular structure using self
      interaction corrected density functional calculations. Optical excitation at 226
      nm launches an oscillatory wavepacket in the amine umbrella coordinate with a 650
      fs period. Even though the Franck-Condon excitation is at an angle of 17 degrees
      , the wavepacket settles into an oscillation between 4 degrees  and -10 degrees 
      within a fraction of a vibrational period and then dephases with a time constant
      of 750 fs.

PMID- 28742349
TI  - Exploring the Sponge Consortium Plakortis symbiotica-Xestospongia deweerdtae as a
      Potential Source of Antimicrobial Compounds and Probing the Pharmacophore for
      Antituberculosis Activity of Smenothiazole A by Diverted Total Synthesis.
AB  - Fractionation of the bioactive CHCl3-MeOH (1:1) extracts obtained from two
      collections of the sponge consortium Plakortis symbiotica-Xestospongia deweerdtae
      from Puerto Rico provided two new plakinidone analogues, designated as
      plakinidone B (2) and plakinidone C (3), as well as the known plakinidone (1),
      plakortolide F (4), and smenothiazole A (5). The structures of 1-5 were
      characterized on the basis of 1D and 2D NMR spectroscopic, IR, UV, and HRMS
      analysis. The absolute configurations of plakinidones 2 and 3 were established
      through chemical correlation methods, VCD/ECD experiments, and spectroscopic data
      comparisons. When assayed in vitro against Mycobacterium tuberculosis H37Rv, none
      of the plakinidones 1-3 displayed significant activity, whereas smenothiazole A
      (5) was the most active compound, exhibiting an MIC value of 4.1 MUg/mL.
      Synthesis and subsequent biological screening of 8, a dechlorinated version of
      smenothiazole A, revealed that the chlorine atom in 5 is indispensable for anti
      TB activity.

PMID- 28742350
TI  - Complexation Behavior of Polyelectrolytes and Polyampholytes.
AB  - We perform grand canonical Monte Carlo simulations to study the pH titrations of
      isolated polyampholytes and polyelectrolyte-polyampholyte complexes in dilute
      solutions. Our simulations indicate that the electrostatic interactions promote
      the coexistence of opposite charges along the polyampholyte chain during
      titration. The repulsion between excess charges typically dominates the
      electrostatic interaction and leads to polymer stretching. Salt ions can screen
      the repulsion between excess charges as well as the fluctuation-induced
      attraction between opposite charges, and therefore make the variation between
      titration curves of polyampholytes and the ideal (no electrostatic interactions)
      curves less significant. We observe that this screening of charge repulsion
      decreases the chain size. The presence of pearl-necklace configuration of
      polyampholytes is diminished by the addition of salt. Similar simulations for the
      polyelectrolyte-polyampholyte system show that the resulting complexes are
      generally stable in the low pH region. In comparison to ideal case, electrostatic
      interactions strongly influence the acid-base properties of polyampholyte chains
      in the adsorbed state by reducing the presence of the coexistence domain of both
      positive and negative charges in the titration curves. We attribute the complex
      formation between polyelectrolyte and polyampholyte chains in the high pH region
      to, e.g., the high salt content. The pH variation leads to abrupt transition
      between adsorbed and desorbed states. Independent of charge sequence, a
      polyampholyte chain in a complex is usually located at one of the ends of the
      polyelectrolyte chain.

PMID- 28742351
TI  - Materials Screening for the Discovery of New Half-Heuslers: Machine Learning
      versus ab Initio Methods.
AB  - Machine learning (ML) is increasingly becoming a helpful tool in the search for
      novel functional compounds. Here we use classification via random forests to
      predict the stability of half-Heusler (HH) compounds, using only experimentally
      reported compounds as a training set. Cross-validation yields an excellent
      agreement between the fraction of compounds classified as stable and the actual
      fraction of truly stable compounds in the ICSD. The ML model is then employed to
      screen 71 178 different 1:1:1 compositions, yielding 481 likely stable
      candidates. The predicted stability of HH compounds from three previous high
      throughput ab initio studies is critically analyzed from the perspective of the
      alternative ML approach. The incomplete consistency among the three separate ab
      initio studies and between them and the ML predictions suggests that additional
      factors beyond those considered by ab initio phase stability calculations might
      be determinant to the stability of the compounds. Such factors can include
      configurational entropies and quasiharmonic contributions.

PMID- 28742352
TI  - Stereocontrolled Nucleophilic Addition to Five-Membered Oxocarbenium Ions
      Directed by the Protecting Groups. Application to the Total Synthesis of (+)
      Varitriol and of Two Diastereoisomers Thereof.
AB  - A stereodivergent C-glycosidation of carbohydrate-derived lactones can be
      mediated by the protecting groups and applied to the total synthesis of (+)
      varitriol and of two diastereoisomers thereof, which represent an unprecedent use
      of the protecting groups in the synthesis of a naturally occurring compound. In
      particular, the stereoselective nucleophile attack for 2,3-trans-substituted five
      membered ring oxocarbenium ions is strongly influenced by the presence of
      aromatic rings in the protecting groups. According to quantum chemical
      calculations, the stereoselectvity depends on the pi-pi interactions between the
      aromatic ring of the C-2 protecting group with the exocyclic triple bond and the
      oxocarbenium ion. These interactions account for the stabilization of the
      conformer in which the C-2 and C-3 substituents adopt pseudoaxial orientations.
      When protecting groups do not contain an aromatic ring, the sterochemical outcome
      is dictated by stereoelectronic factors established by the Woerpel's model. Based
      on these findings, a concise total synthesis of the natural product (+)-varitriol
      and of two diastereoisomers was acomplished.

PMID- 28742353
TI  - Density Functional Theory Assessment of the Environment Polarity Effect on
      Polyaniline-Water Coupling.
AB  - Crystallization water plays an important role in the self-organization of
      oligomer chains in conducting polyaniline. In order to quantify the interaction
      between emeraldine salt and such a water, models containing a tetramer in
      bipolaronic or polaronic form, chloride counterions, and an explicit water
      molecule are used. Different initial positions of water with respect to the
      oligomer chain-tangential and vertical-are considered. Various media are
      simulated by introducing an implicit solvent continuum of decreasing polarity.
      The DFT-D3/PCM computational approach is employed to examine the behavior of the
      systems in several aspects-the role of the explicit water position and the effect
      of the environment polarity on the spatial structure, energetics, charge
      distribution, and the frontier molecular orbital energies. The strength of
      hydrogen bonding and the patterns of charge redistribution invoked by the water
      molecule are discussed. The study establishes trend lines in the variation of the
      molecular characteristics upon change of milieu as a tool for control of the self
      assembly process. The results show that chains interact more efficiently with
      tangentially placed water. The influence of the environment polarity is minor and
      is mainly expressed in slight shortening of the intermolecular distances and mild
      decrease of the group charges of the system components with reduction of
      polarity.

PMID- 28742354
TI  - Germanium Dicarbide: Evidence for a T-Shaped Ground State Structure.
AB  - The equilibrium structure of germanium dicarbide GeC2 has been an open question
      since the late 1950s. Although most high-level quantum calculations predict an L
      shaped geometry, a T-shaped or even a linear geometry cannot be ruled out because
      of the very flat potential energy surface. By recording the rotational spectrum
      of this dicarbide using sensitive microwave and millimeter techniques, we
      unambiguously establish that GeC2 adopts a vibrationally averaged T-shaped
      structure in its ground state. From analysis of 14 isotopologues, a precise r0
      structure has been derived, yielding a Ge-C bond length of 1.952(1) A and an apex
      angle of 38.7(2) degrees .

PMID- 28742355
TI  - TFSI and TDI Anions: Probes for Solvate Ionic Liquid and Disproportionation-Based
      Lithium Battery Electrolytes.
AB  - Highly concentrated electrolytes based on Li-salts and chelating solvents, such
      as glymes, are promising as electrolytes for lithium batteries. This is due to
      their unique properties, such as higher electrochemical stabilities, compliance
      with high-voltage electrodes, low volatility and flammability, and inertness
      toward aluminum current collector corrosion. The nature of these properties
      originates from the molecular-level structure created in either solvate ionic
      liquids (SILs) or the less common ionic aggregates by disproportionation
      reactions. The nature of the anion plays a crucial role, and here, we present a
      computational study using TFSI and TDI anions as probes, revealing increasing
      differences upon increased salt concentration. TFSI-based electrolytes preferably
      form SILs, while TDI-based electrolytes form ionic aggregates. The latter lead to
      an unexpected creation of "free" cationic species even at (very) high salt
      concentrations and thus promise of ample lithium ion transport.

PMID- 28742356
TI  - Quantum Melting and Isotope Effects from Diffusion Monte Carlo Studies of p-H2
      Clusters.
AB  - We present a rigorous characterization of the ground state structures of p-H2
      clusters and their isotopologues using diffusion Monte Carlo combined with the
      inherent structures analysis. For the N = 19 cluster we explore the effect of
      "quantum melting" by quantifying the contributions of local minima to the ground
      state as a function of continuously varying particle mass. Doubling the cluster
      size leads to an enormous increase of its complexity: the ground state of (p
      H2)38 is highly delocalized over a large number of minima representing all the
      funnels of the potential energy surface. The ground state of (o-D2)38 is also
      delocalized, but over a smaller subset of minima, which exclusively belong to the
      same disordered motif.

PMID- 28742357
TI  - Size Effect in the Ionization Energy of PAH Clusters.
AB  - We report the first experimental measurement of the near-threshold
      photoionization spectra of polycyclic aromatic hydrocarbon clusters made of
      pyrene C16H10 and coronene C24H12, obtained using imaging photoelectron-photoion
      coincidence spectrometry with a VUV synchrotron beamline. The experimental
      results of the ionization energy are compared to calculated ones obtained from
      simulations using dedicated electronic structure treatment for large ionized
      molecular clusters. Experiment and theory consistently find a decrease of the
      ionization energy with cluster size. The inclusion of temperature effects in the
      simulations leads to a lowering of this energy and to quantitative agreement with
      the experiment. In the case of pyrene, both theory and experiment show a
      discontinuity in the IE trend for the hexamer. This work demonstrates the ability
      of the models to describe the electronic structure of PAH clusters and suggests
      that these species are ionized in astronomical environments where they are
      thought to be present.

PMID- 28742358
TI  - Swelling of Random Copolymer Networks in Pure and Mixed Solvents: Multi-Component
      Flory-Rehner Theory.
AB  - A generalized extension of Flory-Rehner (FR) theory is derived to describe
      equilibrium swelling of polymer networks, including copolymers with two or more
      chemically distinct repeat units, in either pure or mixed solvents. The model is
      derived by equating the chemical potential of each solvent in the liquid and gel
      phases at equilibrium, while assuming the deformation of the network chains is
      affine. Simplifications of the model are derived for specific cases involving
      homopolymer networks, copolymer networks, pure solvents, and binary solvent
      mixtures. With reasonable assumptions, the number of polymer-solvent interaction
      parameters that must be determined by experiments can be reduced to two effective
      parameters (theta1 and theta2), which describe the net interactions between
      water/copolymer (theta1) and ethanol/copolymer (theta2), respectively.
      Experimental measurements of the swelling of random copolymer networks of n-butyl
      acrylate and 2-hydroxyethyl acrylate in water, ethanol, and a 100 g/L
      ethanol/water mixture are utilized to validate the model. For a random copolymer
      network, theta1 and theta2 can be obtained by fitting the three-component FR
      model to equilibrium swelling data obtained in the pure solvents. Predicted
      solvent volume fractions for swelling in water-ethanol mixtures obtained by
      inserting fitted values of theta1 and theta2 into the four-component FR model are
      in reasonable agreement with experimental measurements.

PMID- 28742359
TI  - Pressure-Induced Structural and Optical Properties of Inorganic Halide Perovskite
      CsPbBr3.
AB  - Perovskite photovoltaic materials are gaining sustained attention because of
      their excellent photovoltaic properties and extensive practical applicability. In
      this Letter, we discuss the changes in the structure and optical properties of
      CsPbBr3 under high pressure. As the pressure increased, the band gap initially
      began to red shift before 1.0 GPa followed by a continuous blue shift until the
      crystal was completely amorphized. An isostructural phase transition at 1.2 GPa
      was determined by high-pressure synchrotron X-ray and Raman spectroscopy. The
      result could be attributed to bond length shrinkage and PbBr6 octahedral
      distortion under high pressure. The amorphization of the crystal was due to the
      severe distortion and tilt of the PbBr6 octahedron, leading to broken long-range
      order. Changes in optical properties are closely related to the evolution of the
      crystal structure. Our discussion shows that high-pressure study can be used as
      an effective means to tune the structure and properties of all-inorganic halide
      perovskites.

PMID- 28742360
TI  - Chiral Bronsted Acid Catalyzed Enantioselective aza-Friedel-Crafts Reaction of
      Cyclic alpha-Diaryl N-Acyl Imines with Indoles.
AB  - Asymmetric addition of indoles to cyclic alpha-diaryl-substituted N-acyl imines,
      which are generated in situ from 3-aryl 3-hydroxyisoindolinones, is described.
      The transformation proceeds smoothly with a broad range of indoles and
      isoindolinone alcohols using a SPINOL-derived chiral Bronsted acid catalyst to
      afford alpha-tetrasubstituted (3-indolyl)(diaryl)methanamines in excellent yields
      and enantioselectivities (up to 98% yield, up to >99:1 e.r.). The origin of
      stereochemical induction is supported by DFT calculations and experimental data.

PMID- 28742361
TI  - Kinetic-Dominated Charging Mechanism within Representative Aqueous Electrolyte
      based Electric Double-Layer Capacitors.
AB  - The chemical nature of electrolytes has been demonstrated to play a pivotal role
      in the charge storage of electric double-layer capacitors (EDLCs), whereas
      primary mechanisms are still partially resolved but controversial. In this work,
      a systematic exploration into EDL structures and kinetics of representative
      aqueous electrolytes is performed with numerical simulation and experimental
      research. Unusually, a novel charging mechanism exclusively predominated by
      kinetics is recognized, going beyond traditional views of manipulating
      capacitances preferentially via interfacial structural variations. Specifically,
      strikingly distinctive EDL structures stimulated by diverse ion sizes, valences,
      and mixtures manifest a virtually identical EDL capacitance, where the dielectric
      nature of solvents attenuates ionic effects on electrolyte redistributions, in
      stark contradiction with solvent-free counterpart and traditional Helmholtz
      theory. Meanwhile, corresponding kinetics evolve conspicuously with ionic
      species, intimately correlated with ion-solvent interactions. The achieved
      mechanisms are subsequently illuminated by electrochemical measurements,
      highlighting the crucial interplay between ions and solvents in regulating EDLC
      performances.

PMID- 28742362
TI  - Convective Self-Sustained Motion in Mixtures of Chemically Active and Passive
      Particles.
AB  - We develop a model to describe the behavior of a system of active and passive
      particles in solution that can undergo spontaneous self-organization and self
      sustained motion. The active particles are uniformly coated with a catalyst that
      decomposes the reagent in the surrounding fluid. The resulting variations in the
      fluid density give rise to a convective flow around the active particles. The
      generated fluid flow, in turn, drives the self-organization of both the active
      and passive particles into clusters that undergo self-sustained propulsion along
      the bottom wall of a microchamber. This propulsion continues until the reagents
      in the solution are consumed. Depending on the number of active and passive
      particles and the structure of the self-organized cluster, these assemblies can
      translate, spin, or remain stationary. We also illustrate a scenario in which the
      geometry of the container is harnessed to direct the motion of a self-organized,
      self-propelled cluster. The findings provide guidelines for creating autonomously
      moving active particles, or chemical "motors" that can transport passive cargo in
      microfluidic devices.

PMID- 28742363
TI  - Improved Performance of Glucose Bioanodes Using Composites of (7,6) Single-Walled
      Carbon Nanotubes and a Ferrocene-LPEI Redox Polymer.
AB  - The effect of incorporating different types of carbon nanotubes into composite
      films of a redox polymer (FcMe2-C3-LPEI) and glucose oxidase (GOX) was
      investigated. The composite films were constructed by first forming a high
      surface area network film of either single-walled carbon nanotubes (SWNTs) or
      multiwalled carbon nanotubes (MWNTs) on a glassy carbon electrode (GCE) by
      solution casting of a suspension of Triton-X-100 dispersed SWNTs. Next a glucose
      responsive redox hydrogel was formed on top of the nanotube-modified electrode by
      cross-linking FcMe2-C3-LPEI with glucose oxidase via ethylene glycol diglycidyl
      ether (EGDGE). Electrochemical and enzymatic measurements showed that composite
      films made with (7,6) SWNTs produced a higher response (3.3 mA/cm2) to glucose
      than films made with (6,5) SWNTs (1.8 mA/cm2) or MWNTs (1.2 mA/cm2) or films made
      without SWNTs (0.7 mA/cm2). We also show that the response of the composite films
      could be systematically varied by fabricating SWNT films with different weight
      ratios of (7,6) and (6,5) SWNTs. Optimization of the (7,6) SWNTs loading and the
      redox polymer-enzyme film produced a glucose response of 11.2 mA/cm2. Combining
      the optimized glucose films with a platinum oxygen breathing cathode into a
      biofuel cell produced a maximum power density output of 343 MUW/cm2.

PMID- 28742364
TI  - Solvent Exchange Leading to Nanobubble Nucleation: A Molecular Dynamics Study.
AB  - The solvent exchange procedure has become the most-used protocol to produce
      surface nanobubbles, while the molecular mechanisms behind the solvent exchange
      are far from being fully understood. In this paper, we build a simple model and
      use molecular dynamics simulations to investigate the dynamic characteristics of
      solvent exchange for producing nanobubbles. We find that at the first stage of
      solvent exchange, there exists an interface between interchanging solvents of
      different gas solubility. This interface moves toward the substrate gradually as
      the exchange process proceeds. Our simulations reveal directed diffusion of gas
      molecules against the gas concentration gradient, driven by the solubility
      gradient of the liquid composition across the moving solvent-solvent interface.
      It is this directed diffusion that causes gas retention and produces a local gas
      oversaturation much higher near the substrate than far from it. At the second
      stage of solvent exchange, the high local gas oversaturation leads to bubble
      nucleation either on the solid surface or in the bulk solution, which is found to
      depend on the substrate hydrophobicity and the degree of local gas
      oversaturation. Our findings suggest that solvent exchange could be developed
      into a standard procedure to produce oversaturation and used to a variety of
      nucleation applications other than generating nanobubbles.

PMID- 28742365
TI  - Divergent Synthesis of Polycyclic Indolines: Copper-Catalyzed Cascade Reactions
      of Propargylic Carbamates and Indoles.
AB  - Polycyclic indolines are the common and core structural motif of many indole
      alkaloids that usually exhibit biological activities. Here, we describe two
      copper-catalyzed cascade reactions between propargylic carbamates and indoles. By
      doing so, one-step and divergent synthesis of structurally distinct polycyclic
      indolines, quinoline-fused indolines, C(3a)-indolyl furoindolines, and
      pyrroloindolines was achieved in high synthetic efficiency and selectivity.

PMID- 28742366
TI  - Femtosecond-Laser-Enhanced Amyloid Fibril Formation of Insulin.
AB  - Femtosecond (fs)-laser-induced crystallization as a novel crystallization
      technique was proposed for the first time by our group, where the crystallization
      time can be significantly shortened under fs laser irradiation. Similarly, we
      have further extended our investigation to amyloid fibril formation, also known
      as a nucleation-dependence process. Here we demonstrate that the necessary time
      for amyloid fibril formation can be significantly shortened by fs laser
      irradiation, leading to favorable enhancement. The enhancement was confirmed by
      both spectral measurements and direct observations of amyloid fibrils. The
      thioflavin T fluorescence intensity of laser-irradiated solution increased
      earlier than that of the control solution, and such a difference was
      simultaneously revealed by ellipticity changes. At the same time before intensity
      saturation in fluorescence, the number of amyloid fibrils obtained under laser
      irradiation was generally more than that in the control solution. Besides, such
      an enhancement is correlated to the laser power threshold of cavitation bubbling.
      Possible mechanisms are proposed by referring to fs-laser-induced crystallization
      and ultrasonication-induced amyloid fibril formation.

PMID- 28742367
TI  - Long-Lived Direct and Indirect Interlayer Excitons in van der Waals
      Heterostructures.
AB  - We report the observation of a doublet structure in the low-temperature
      photoluminescence of interlayer excitons in heterostructures consisting of
      monolayer MoSe2 and WSe2. Both peaks exhibit long photoluminescence lifetimes of
      several tens of nanoseconds up to 100 ns verifying the interlayer nature of the
      excitons. The energy and line width of both peaks show unusual temperature and
      power dependences. While the low-energy peak dominates the spectra at low power
      and low temperatures, the high-energy peak dominates for high power and
      temperature. We explain the findings by two kinds of interlayer excitons being
      either indirect or quasi-direct in reciprocal space. Our results provide
      fundamental insights into long-lived interlayer states in van der Waals
      heterostructures with possible bosonic many-body interactions.

PMID- 28742368
TI  - Borapetoside E, a Clerodane Diterpenoid Extracted from Tinospora crispa, Improves
      Hyperglycemia and Hyperlipidemia in High-Fat-Diet-Induced Type 2 Diabetes Mice.
AB  - An insidious increase in the incidence of obesity, insulin resistance, and
      hyperlipidemia has led to an epidemic of type 2 diabetes worldwide. Tinospora
      crispa (T. crispa) is a familiar plant traditionally used in herbal medicine for
      diabetes; however, the major active ingredients of this plant are still unclear.
      In this study, we identified the therapeutic effects of borapetoside E, a small
      molecule extracted from T. crispa, in high-fat-diet (HFD)-induced obesity in
      mice. The therapeutic effects of borapetoside E in HFD-induced obese mice were
      assessed physiologically, histologically, and biochemically following
      intraperitoneal injection. Furthermore, we analyzed the expression of glucose and
      lipid metabolism-related genes and proteins in borapetoside E-treated obese mice.
      Compared with vehicle-treated mice, borapetoside E markedly improved
      hyperglycemia, insulin resistance, hepatic steatosis, hyperlipidemia, and oxygen
      consumption in obese mice, and the effects were comparable to or better than the
      drug metformin. In addition, borapetoside E suppressed the expression of sterol
      regulatory element binding proteins (SREBPs) and their downstream target genes
      related to lipid synthesis in the liver and adipose tissue. Borapetoside E showed
      beneficial effects in vivo, demonstrating that borapetoside E may be a potential
      therapy for the treatment of diet-induced type 2 diabetes and related metabolic
      syndromes.

PMID- 28742369
TI  - Effect of Curcumin Addition on the Adsorption and Transport of a Cationic Dye
      across DPPG-POPG Liposomes Probed by Second Harmonic Spectroscopy.
AB  - The effect of addition of curcumin on the adsorption and transport
      characteristics of a cationic dye, LDS+, across negatively charged bilayers
      composed of POPG and DPPG lipids were investigated by the interface selective
      second harmonic (SH) spectroscopic technique. Curcumin induced changes in the SH
      electric field signal of the LDS+ ions (E2omega (LDS+)) were observed to depend
      critically on the bilayer acyl chain saturation/unsaturation ratio (S/U).
      Following earlier works, the increase in the E2omega (LDS+) signal is attributed
      to the release of the Na+ counterions present in the head group region of the
      bilayer by curcumin and the decay of the E2omega (LDS+) signal is attributed to
      the bilayer intercalated state of curcumin. While the changes observed in the
      E2omega (LDS+) signal in the presence of POPG liposomes were consistent with our
      earlier study ( Varshney, G. K. et al. Langmuir , 2016 , 32 , 10415 - 10421 ),
      they were significantly different for DPPG liposomes, following curcumin
      addition. While the increase in the E2omega (LDS+) signal in the presence of POPG
      liposomes, is marginal (~10-20%) and instantaneous (<1 s) followed by a rapid
      decay (completed within ~100 s), in the presence of DPPG liposomes it was
      observed to increase slowly and at saturation shows a substantial increase (100
      200%), following curcumin addition. When liposomes consisting of a mixture of
      POPG and DPPG lipids are used, curcumin induced kinetic characteristics of the
      E2omega (LDS+) signal showed a mixture of the individual kinetic characteristics
      observed for the unsaturated (POPG) and saturated (DPPG) liposomes. The observed
      kinetic trends of the E2omega (LDS+) signal following curcumin addition are
      explained on the basis of the relative strength of the Na+-POPG and Na+-DPPG
      interaction. Higher ordering of the lipid acyl chain region in DPPG liposome
      makes the Na+-DPPG interaction much stronger than the Na+-POPG interaction.
      Further, it is proposed that, in POPG-DPPG liposomes, individual domains of POPG
      and DPPG lipids exist at low temperature as suggested by the observed temperature
      dependent kinetic characteristics of the E2omega (LDS+) signal following curcumin
      addition. These domains are dependent on the S/U ratio and phase state of the
      bilayer. The gel phase was observed to be more conducive for individual domain
      formation. Results presented in this work not only support the notion that
      biological activity of curcumin is associated with its bilayer altering
      properties, but more interestingly it provides a qualitative insight about how
      bilayer phase separation can be achieved by modulating the hydrophobic
      interactions between the lipid acyl chains.

PMID- 28742370
TI  - A Community Grows around the Geysering World of Enceladus.
AB  - The discovery by NASA's Cassini mission at Saturn in 2005 of a large plume of
      material erupting from the south polar terrain of Enceladus, sourced within a
      subsurface ocean of salty liquid water laced with organic compounds, has brought
      together scientists from a diverse range of disciplines over the last decade to
      evaluate this small moon's potential for extraterrestrial life. The collection of
      papers published today in Astrobiology, as the mission draws to a close, is the
      outcome of our most recent meeting at UC Berkeley in June 2016. Key Words:
      Enceladus-Enceladus Focus Group-Ocean world-Search for biosignatures.
      Astrobiology 17, 815-819.

PMID- 28742371
TI  - Correcting the "Wandering" Neutrophil with Statins. A Novel Antiaging Strategy?

PMID- 28742372
TI  - Health Care Price Transparency and Communication: Implications for Radiologists
      and Patients in an Era of Expanding Shared Decision Making.
AB  - OBJECTIVE: The purpose of this article is to review the literature on
      communicating transparency in health care pricing, both overall and specifically
      for medical imaging. Focus is also placed on the imperatives and initiatives that
      will increasingly impact radiologists and their patients. CONCLUSION: Most
      Americans seek transparency in health care pricing, yet such discussions occur in
      fewer than half of patient encounters. Although price transparency tools can help
      decrease health care spending, most are used infrequently and most lack
      information about quality. Given the high costs associated with many imaging
      services, radiologists should be aware of such initiatives to optimize patient
      engagement and informed shared decision making.

PMID- 28742373
TI  - Utility of MRI to Differentiate Clear Cell Renal Cell Carcinoma Adrenal
      Metastases From Adrenal Adenomas.
AB  - OBJECTIVE: The purpose of this study is to compare MRI features of clear cell
      renal cell carcinoma (RCC) adrenal metastases and adenomas. MATERIALS AND
      METHODS: Fifteen clear cell RCC adrenal metastases imaged with MRI were compared
      to 29 consecutive adenomas between 2006 and 2015. Two blinded radiologists
      assessed homogeneity (homogeneous vs heterogeneous), signal intensity (SI)
      decrease on chemical-shift MRI, and T2-weighted SI (isointense, mildly
      hyperintense, or markedly hyperintense) relative to muscle. A third blinded
      radiologist measured the chemical-shift SI index, adrenal-to-spleen SI ratio, T2
      weighted SI ratio, AUC for contrast-enhanced MRI, and histogram analysis.
      Analyses were performed using chi-square, linear regression, ROC, and logistic
      regression modeling. RESULTS: Clear cell RCC metastases were larger than adenomas
      (mean [+/- SD], 5.0 +/- 4.2 cm [range, 1.1-15 cm] vs 2.0 +/- 0.7 cm [range, 1.2
      3.7 cm]; p < 0.0001). Subjectively, 33.3% (5/15) of metastases and 68.9% (20/29)
      of adenomas showed an SI decrease on chemical-shift MRI (p = 0.0421; kappa =
      0.76). Chemical-shift SI index (mean, 9.2% +/- 20.6%; range, -30.0% to 57.9%) and
      adrenal-to-spleen SI ratio (0.94 +/- 0.23 [range, 0.44-1.33]) for metastases
      differed significantly from those for adenomas (47.3% +/- 27.8% [range, -9.4% to
      86%] and 0.52 +/- 0.28 [range, 0.13-1.11], respectively) (p < 0.0001). Twenty
      percent (3/15) of metastases had chemical-shift SI index in the adenoma range (>
      16.5%). Metastases had higher T2-weighted SI than did adenomas, both
      quantitatively (5.1 +/- 3.0 [range, 1.5-10.6] vs 1.8 +/- 0.8 [range, 0.5-3.8]; p
      < 0.0001) and subjectively (p < 0.0001; kappa = 0.89). Metastases had higher
      entropy than did adenomas (6.76 +/- 0.61 vs 6.1 +/- 0.74; p = 0.0051) and were
      subjectively more heterogeneous (p < 0.0001; kappa = 0.86). The contrast-enhanced
      MRI AUC, skewness, and kurtosis did not differ between groups (p > 0.05). The ROC
      AUCs were 0.91 (95% CI, 0.79-1.0) for T2-weighted SI ratio and 0.85 (95% CI, 0.68
      1.0) for entropy. The logistic regression model of T2-weighted SI ratio plus
      entropy improved accuracy (ROC AUC, 0.97; 95% CI, 0.93-1.0]) compared with either
      feature alone (p = 0.0215). CONCLUSION: Increased T2-weighted SI and
      heterogeneity are features that can differentiate clear cell RCC adrenal
      metastases from adenomas using quantitative and subjective analysis.

PMID- 28742374
TI  - High-Throughput Analysis Identifying Drugs That Regulate Apolipoprotein A-I
      Synthesis.
AB  - Apolipoprotein A-I (apo A-I) is the primary antiatherogenic protein in high
      density lipoprotein (HDL). Despite the controversy as to the clinical
      effectiveness of raising HDL, the search is ongoing for safe and effective drugs
      that increase HDL and apo A-I levels. To identify novel compounds that can
      increase hepatic apo A-I production, two drug libraries were screened. The NIH
      clinical collection (NCC) and the NIH clinical collection 2 (NCC2) were purchased
      from Evotec (San Francisco, CA). The NCC library contains 446 compounds and the
      NCC2 library contains 281 compounds, all dissolved in dimethylsulfoxide at a
      concentration of 10 mM. Hepatoma-derived cells (HepG2) and primary hepatocytes in
      culture were treated with various compounds for 24 h and apo A-I in media samples
      was measured by enzyme immunoassay. Samples with significant changes in apo A-I
      concentrations were retested in independent experiments by Western blot analysis
      to confirm the immunoassay findings. Of a total of 727 compounds screened at a
      concentration of 50 MUM, 15 compounds increased hepatic apo A-I production by 35%
      54%, and 9 compounds lowered hepatic apo A-I concentrations in the culture media
      by 25%-52%. Future trials should explore the clinical effectiveness of these
      agents when standard doses of these drugs are used in humans.

PMID- 28742375
TI  - Continuous Negative Abdominal Pressure Recruits Lungs at Lower Distending
      Pressures.

PMID- 28742376
TI  - Hypervascular Transformation of Hypovascular Hypointense Nodules in the
      Hepatobiliary Phase of Gadoxetic Acid-Enhanced MRI: A Systematic Review and Meta
      Analysis.
AB  - OBJECTIVE: The purpose of this study is to evaluate the outcomes of hypovascular
      hypointense nodules in the hepatobiliary phase of gadoxetic acid-enhanced MRI and
      the risk factors for the hypervascular transformation of the nodules through a
      systematic review and meta-analysis. MATERIALS AND METHODS: We searched the Ovid
      MEDLINE and EMBASE databases for published studies of hypovascular hypointense
      nodules in patients with chronic liver disease. The pooled proportions of the
      overall and cumulative incidence rates at 1, 2, and 3 years for the
      transformation of hypovascular hypointense nodules into hypervascular
      hepatocellular carcinomas (HCCs) were assessed by using random-effects modeling.
      Metaregression analysis was performed. RESULTS: Sixteen eligible studies with 944
      patients and 1819 hypovascular hypointense nodules in total were included. The
      pooled overall rate of hypervascular transformation was 28.2% (95% CI, 22.7
      33.6%; I2 = 87.46%). The pooled 1-, 2-, and 3-year cumulative incidence rates
      were 18.3% (95% CI, 9.2-27.4%), 25.2% (95% CI, 12.2-38.2%), and 30.3% (95% CI,
      18.8-41.9%), respectively. The metaregression analysis revealed that the mean
      initial nodule size (cutoff value, 9 mm) was a significant factor affecting the
      heterogeneity of malignant transformation. CONCLUSION: Hypovascular hypointense
      nodules detected in the hepatobiliary phase of gadoxetic acid-enhanced MRI carry
      a significant potential of transforming into hypervascular HCCs. The size of
      nodules is a significant risk factor for hypervascular transformation.

PMID- 28742377
TI  - Reducing Delay in Diagnosis: Multistage Recommendation Tracking.
AB  - OBJECTIVE: The purpose of this study was to determine whether a multistage
      tracking system could improve communication between health care providers,
      reducing the risk of delay in diagnosis related to inconsistent communication and
      tracking of radiology follow-up recommendations. MATERIALS AND METHODS:
      Unconditional recommendations for imaging follow-up of all diagnostic imaging
      modalities excluding mammography (n = 589) were entered into a database and
      tracked through a multistage tracking system for 13 months. Tracking
      interventions were performed for patients for whom completion of recommended
      follow-up imaging could not be identified 1 month after the recommendation due
      date. Postintervention compliance with the follow-up recommendation required
      examination completion or clinical closure (i.e., biopsy, limited life expectancy
      or death, or subspecialist referral). RESULTS: Baseline radiology information
      system checks performed 1 month after the recommendation due date revealed timely
      completion of 43.1% of recommended imaging studies at our institution before
      intervention. Three separate tracking interventions were studied, showing
      effectiveness between 29.0% and 57.8%. The multistage tracking system increased
      the examination completion rate to 70.5% (a 52% increase) and reduced the rate of
      unknown follow-up compliance and the associated risk of delay in diagnosis to
      13.9% (a 74% decrease). Examinations completed after tracking intervention
      generated revenue of 4.1 times greater than the labor cost. CONCLUSION:
      Performing sequential radiology recommendation tracking interventions can
      substantially reduce the rate of unknown follow-up compliance and add value to
      the health system. Unknown follow-up compliance is a risk factor for delay in
      diagnosis, a form of preventable medical error commonly identified in malpractice
      claims involving radiologists and office-based practitioners.

PMID- 28742378
TI  - Effect of the Various Steps in the Processing of Human Milk in the Concentrations
      of IgA, IgM, and Lactoferrin.
AB  - INTRODUCTION: Human milk immune components are unique and important for the
      development of the newborn. Milk processing at the Human Milk Banks (HMB),
      however, causes partial destruction of immune proteins. The objective of this
      study was to determine the effects that heating during the milk processing
      procedure at the HMB had on the concentrations of IgA, IgM, and lactoferrin at
      three critical points in time. MATERIALS AND METHODS: Fifty milk samples (150 mL)
      were collected from voluntary donors at the HMB at the Hospital Nacional Pedro de
      Bethancourt, located in Antigua Guatemala. Samples from three critical points in
      time during the milk processing procedure were selected for analysis:
      freezing/thawing I, freezing/thawing II, and pasteurization. IgA, IgM, and
      lactoferrin concentrations were determined during each critical point and
      compared with a baseline concentration. RESULTS: After milk processing, IgA, IgM,
      and lactoferrin mean concentrations were reduced by 30.0%, 36.0%, and 70.0%,
      respectively (p < 0.001). Reduction of biological activity was mainly attributed
      to pasteurization for IgA and lactoferrin (p < 0.001); the first freezing/thawing
      processes before pasteurization showed no significant reduction difference
      between mean concentrations of IgA (p = 0.160) and lactoferrin (p = 0.345) but
      showed a significant effect on IgM concentration (p = 0.016), and the second
      freezing/thawing procedure only showed a significant effect on IgA (p < 0.001).
      CONCLUSIONS: The effects of milk processing on the immune proteins that were
      evaluated in this study demonstrated a significant reduction.

PMID- 28742379
TI  - Caffeine: A Lung Drug for All Very Low Birth Weight Preterm Infants?

PMID- 28742380
TI  - The Role of Radiology in the Diagnostic Process: Information, Communication, and
      Teamwork.
AB  - OBJECTIVE: The diagnostic radiology process represents a partnership between
      clinical and radiology teams. As such, breakdowns in interpersonal interactions
      and communication can result in patient harm. CONCLUSION: We explore the role of
      radiology in the diagnostic process, focusing on key concepts of information and
      communication, as well as key interpersonal interactions of teamwork,
      collaboration, and collegiality, all based on trust. We propose 10 principles to
      facilitate effective information flow in the diagnostic process.

PMID- 28742381
TI  - Systemic Error in Radiology.
AB  - OBJECTIVE: Interpretive errors in diagnostic imaging result in significant
      patient morbidity and mortality, but the importance of errors and process
      failures in the imaging cycle other than during image interpretation is
      underappreciated. In this article, we describe these errors and potential
      solutions, providing a framework to improve patient safety and understand the
      changing roles of radiologists beyond image interpretation. CONCLUSION: For
      comprehensive improvements to health care delivery, other failures in the cycle
      besides diagnostic interpretive error-such as ordering inappropriate studies,
      PACS failures, and a lack of accurate clinician contact information (with
      resultant communication failure)-should be recognized as contributors to patient
      harm because they lead to wasted resources and delayed care. By taking ownership
      of the entire imaging cycle, radiologists can increase their net worth to patient
      care and cement their roles as experts in the effective, evidence-based use of
      imaging technologies.

PMID- 28742382
TI  - Occurrence and Antibiotic Susceptibility of Listeria Species and Staphylococcus
      aureus in Cattle Slaughterhouses of Kerala, South India.
AB  - A total of 765 samples were collected from beef carcasses, knives, cutting table
      surfaces, beef, hands, air, and water from four cattle slaughterhouses of Kerala,
      South India, to determine the occurrence and antibiotic susceptibility of
      Listeria species and Staphylococcus aureus. Listeria spp. were isolated from beef
      carcasses (2.0%), knives (3.7%), cutting table surfaces (1.9%), beef (0.7%), and
      water (1.3%). The identified species were Listeria monocytogenes (0.1%), Listeria
      innocua (0.9%), and Listeria ivanovii (0.4%). Most of the Listeria spp. were
      susceptible to majority of the antibiotics tested. The virulence genes were not
      detected in Listeria spp. However, all the L. innocua isolates were found to
      harbor the iap gene. The overall occurrence of S. aureus in slaughterhouses was
      50.8%. The highest occurrence was observed on hands of abattoir workers (79.6%)
      and beef carcasses (59.9%). The isolates were commonly resistant to penicillin
      (38.0%), followed by ceftriaxone (31.9%), ampicillin (29.0%), amoxicillin
      (28.8%), tetracycline (24.4%), and chloramphenicol (23.9%). Overall, 53.0% of S.
      aureus isolates were resistant to three or more antibiotics. Vancomycin and
      methicillin resistance were observed in 8.5% and 5.4% of S. aureus isolates,
      respectively. Eight methicillin-resistant S. aureus isolates were found to harbor
      the mecA gene. In conclusion, Listeria spp. was only rarely found in the
      slaughterhouse environment and on beef. Nevertheless, the recovery of L.
      monocytogenes from a water reservoir containing sea water that was used to wash
      carcasses indicates the potential risk of contamination of the carcasses with L.
      monocytogenes when using sea water. S. aureus was frequently isolated from
      abattoir workers and beef carcasses, and the occurrence of S. aureus differed
      significantly between slaughterhouses. The high occurrence of S. aureus, which
      were often resistant toward different antibiotics, represents a significant
      public health concern.

PMID- 28742383
TI  - Role of MRI in the Use of an Absorbable Hydrogel Spacer in Men Undergoing
      Radiation Therapy for Prostate Cancer: What the Radiologist Needs to Know.
AB  - OBJECTIVE: Hydrogel spacers have a novel role in the treatment of low- and
      intermediate-risk prostate cancer with dose-escalated radiation therapy. Given
      the growing number of patients undergoing treatment with radiation therapy, the
      use of hydrogel spacers is expected to increase. The purpose of this article is
      to review what a radiologist needs to know about the imaging of hydrogel spacers,
      including MRI technique and appearance on CT and MRI. CONCLUSION: MRI has a
      critical role in the evaluation of hydrogel spacer placement and is used to
      facilitate contouring by the radiation oncologist. The radiologist should be
      familiar with the imaging appearance of hydrogel spacers on CT and MRI to avoid
      interpretation pitfalls and errors.

PMID- 28742384
TI  - Antiproliferative Effects of Red and White Wine Extracts in PC-3 Prostate Cancer
      Cells.
AB  - Experimental and epidemiological studies have shown that antioxidant polyphenols
      can act as chemopreventive agents against prostate cancer. Cabernet Sauvignon and
      Rombola wine were extracted in order to obtain fractions containing different
      classes of compounds. All extracts inhibited the androgen-insensitive human
      prostate cancer cells (PC-3) proliferation in a dose-dependent manner. The most
      potent compounds were selected to be further tested.Treatment of PC-3 cells with
      the selected wine extracts marginally increased the cell distribution in S phase,
      while producing a remarkable induction of autophagy. Finally, the levels of
      glutathione along with the concentration of hydrogen peroxide and nitrogen oxide
      were modulated in the treated cells. Herein, we show that red and wine extracts
      have direct effects on the proliferation, survival, oxidative status, and the
      induction of autophagy of PC-3 cells. Our data may have important implications
      for the design of a more effective adjuvant treatment for prostate cancer
      patients.

PMID- 28742385
TI  - Sequential Therapy of Breast Cancer Cell Lines with Vitamin C and Quercetin
      Improves the Efficacy of Chemotherapeutic Drugs.
AB  - OBJECTIVE: Prevention by antioxidant agents including vitamin C (VC) and
      quercetin (QU), which are nontoxic, cost effective, and physiologically
      bioavailable, is a promising approach in breast cancer handling. The aim of this
      work is to investigate the influence of VC+QU on cytotoxicity profile of
      doxorubicin (DOX) plus paclitaxel (PAC) in breast cancer cells. METHODS: The
      effect of each drug on its own or in combination was evaluated by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Combination
      indexes were calculated using the Chou-Talalay method. Apoptosis and cell cycle
      analysis was investigated by flow cytometric assays. RESULTS: Combination
      treatment with VC+QU plus drugs diminished IC50 value 2.28-7.7 and 10.5-66.6 fold
      in comparison with the drugs and PAC treatment alone, respectively, in all breast
      cancer cells and induced apoptosis at the early stages more than the treatment
      with the drugs alone (P<0.01). A marked reduction in Go/G1 and S phases was
      reported after combination therapy in MDA-MB 231 and MDA-MB 468 cells. MCF-7
      cells demonstrated lower fractions of cells in S phase with no significant
      changes in G2/M phase (P < 0.01). The same treatment produced a significant
      increase in S and G2/M phases in A549 cells (P < 0.001). CONCLUSION: Our results
      emphasized the importance of VC+QU in combination with the drugs to produce a
      synergistic antitumor effect in breast cancer cells.

PMID- 28742386
TI  - Don't Forget the Fungi When Considering Global Catastrophic Biorisks.

PMID- 28742387
TI  - Vitamin D-Loaded Nanostructured Lipid Carrier (NLC): A New Strategy for Enhancing
      Efficacy of Doxorubicin in Breast Cancer Treatment.
AB  - The dangerous dose-dependent side effects of anticancer agents triggered the
      finding of new approaches for elevated chemotherapy efficacy. This study
      investigated the potential application of nanostructured lipid careers (NLCs) in
      increasing vitamin D3 (VitD) effectiveness in breast cancer cell (MCF-7) in
      concurrent administration with doxorubicin (Dox). VitD-loaded NLCs were
      characterized by particle size, zeta potential, Fourier transform infrared
      spectroscopy, and scanning electron microscope. Cytotoxicity and molecular
      effects of formulation were evaluated by MTT, DAPI staining, flow cytometry, and
      real-time quantitative PCR assays. The formulation revealed mean particle size of
      87+/-5 nm with a polydispersity index of 0.24 confirmed by SEM images. The IC50
      values for VitD and Dox were 1.3 +/- 0.04 and 0.65 +/- 0.05 uM, respectively.
      VitD-loaded NLCs decreased the percentage of cell proliferation from 49 +/- 7.2%
      to 37 +/- 5.1% (P < 0.05). Cotreatment of the cells with VitD-loaded NLCs and Dox
      caused over a twofold increase in the percentage of apoptosis (P < 0.05). Gene
      expression profile demonstrated a significant decrease in antiapoptotic factor
      survivin along with increase in proapoptotic factor Bax mRNA levels. Overall, our
      results introduced the NLC technology as a novel strategy to elevate the efficacy
      of chemotherapeutics in breast cancer.

PMID- 28742388
TI  - How Should We Define Global Catastrophic Biological Risks?

PMID- 28742389
TI  - Emerging and Converging Global Catastrophic Biological Risks.

PMID- 28742391
TI  - Preface: Selected Papers from the Workshop Bioinformatics and Artificial
      Intelligence Joined with the International Joint Conference on Artificial
      Intelligence.

PMID- 28742392
TI  - T-GOWler: Discovering Generalized Process Models Within Texts.
AB  - Contemporary workflow management systems are driven by explicit process models
      specifying the interdependencies between tasks. Creating these models is a
      challenging and time-consuming task. Existing approaches to mining concrete
      workflows into models tackle design aspects related to the diverging abstraction
      levels of the tasks. Concrete workflow logs represent tasks and cases of concrete
      events-partially or totally ordered-grounding hidden multilevel (abstract)
      semantics and contexts. Relevant generalized events could be rediscovered within
      these processes. We propose, in this article, an ontology-based workflow mining
      system to generate patterns from sequences of events that are themselves
      extracted from texts. Our system T-GOWler (Generalized Ontology-based WorkfLow
      minER within Texts) is based on two ontology-based modules: a workflow extractor
      and a pattern miner. To this end, it uses two different ontologies: a domain one
      (to support workflow extraction from texts) and a processual one (to mine
      generalized patterns from extracted workflows).

PMID- 28742393
TI  - Clinical News.

PMID- 28742394
TI  - Assessment of Proteomic Measures Across Serious Psychiatric Illness.
AB  - The diagnoses of serious psychiatric illnesses, such as schizophrenia,
      schizoaffective disorder, and bipolar disorder, rely on the subjective recall and
      interpretation of often overlapping symptoms, and are not based on the objective
      pathophysiology of the illnesses. The subjectivity of symptom reporting and
      interpretation contributes to the delay of accurate diagnoses and limits
      effective treatment of these illnesses. Proteomics, the study of the types and
      quantities of proteins an organism produces, may offer an objective biological
      approach to psychiatric diagnosis. For this pilot study, we used the Myriad RBM
      Discovery Map 250+ platform to quantify 205 serum proteins in subjects with
      schizophrenia (n=26), schizoaffective disorder (n=20), bipolar disorder (n=16),
      and healthy controls with no psychiatric illness (n=23). Fifty-seven analytes
      that differed significantly between groups were used for multivariate modeling
      with linear discriminant analysis (LDA). Diagnoses generated from these models
      were compared to SCID-generated clinical diagnoses to determine whether the
      proteomic markers: 1) distinguished the three disorders from controls, and 2)
      distinguished between the three disorders. We found that a series of binary
      classification models including 8-12 analytes produced separation between all
      subjects and controls, and between each diagnostic group and controls. There was
      a high degree of accuracy in the separations, with training areas-under-the-curve
      (AUC) of 0.94-1.0, and cross-validation AUC of 0.94-0.95. Models with 7-14
      analytes produced separation between the diagnostic groups, though less robustly,
      with training AUC of 0.72-1.0 and validation AUC of 0.69-0.89. While based on a
      small sample size, not adjusted for medication state, these preliminary results
      support the potential of proteomics as a diagnostic aid in psychiatry. The
      separation of schizophrenia, schizoaffective disorder, and bipolar disorder
      suggests that further work in this area is warranted.

PMID- 28742395
TI  - Highlights from the Biennial International Congress on Schizophrenia Research
      (ICOSR), March 24-March 28, 2017.
AB  - The 2017 International Congress on Schizophrenia Research, held in San Diego,
      California (March 24-28, 2017), attracted over 900 attendees from 34 countries.
      With the gracious assistance of Congress president James Meador-Woodruff, we
      bring you the following reports on the prospects for new drugs to treat
      schizophrenia.

PMID- 28742396
TI  - Valbenazine for Tardive Dyskinesia.
AB  - Tardive dyskinesia (TD) remains a clinical concern for any patient who receives
      an antipsychotic. While the overall risk of developing TD is lower with newer
      antipsychotics compared to older agents, a significant number of patients who
      require long-term treatment will develop TD. Recently, valbenazine (brand name
      Ingrezza) became the first drug to be approved by the FDA specifically for the
      treatment of TD. In this New Drug Review, we summarize the basic pharmacology and
      clinical trial results for valbenazine. Valbenazine is a modified metabolite of
      the vesicular monoamine transporter 2 (VMAT-2) inhibitor tetrabenazine, which is
      approved for the treatment of the hyperkinetic movement disorder, Huntington's
      disease. In short-term clinical trials, valbenazine at a dose of 80 mg/day
      improved TD, with an effect size that is clinically significant (d=0.90). The
      effect size for the 40-mg/day dose was lower (d=0.52). Compared to tetrabenazine,
      valbenazine has better clinical characteristics (i.e., once-a-day dosing, better
      short-term side effect profile). However, only long-term experience in routine
      clinical populations can delineate valbenazine's full benefits, optimal dosing,
      and risks not identified during short-term registration trials.

PMID- 28742397
TI  - Morbidity in the Mountainous Province of Kyrgyzstan: Results from a Population
      Based Cross-Sectional Study.
AB  - Brimkulov, Nurlan, Louis Louton, Salima Sydykova, Denis Vinnikov, and Farida
      Imanalieva. Morbidity in the mountainous Province of Kyrgyzstan: Results from a
      population-based cross-sectional study. High Alt Med Biol 18:338-342, 2017.-The
      aim of this study was to identify the main causes of using primary care
      facilities in the mountainous Naryn Province of Kyrgyzstan to set resources
      allocation priorities. We collected data on all admissions to family doctors in
      three Family Medical Centers (FMCs) in Naryn Province: (1) the city of Naryn
      (2200 meters above sea level [MASL]); (2) the town of At-Bashy (3200 MASL); and
      the town of Kochkor (1800 MASL) by using an original questionnaire during one
      full week (5 days) in spring 2016. Within 1 week, we recorded 1136 cases in Naryn
      and 782 cases in Bishkek after exclusion of missing data. The top three reasons
      for admissions were respiratory (23% of all in Naryn and 36% in Bishkek),
      nonspecific general (19% and 17%), and neurological (13% and 9%). Naryn residents
      were 3.84 times (confidence interval [95% CI] 2.07-7.11) more likely to apply
      with musculoskeletal and 3.05 times (95% CI 1.02-9.12) more likely to apply with
      cardiovascular conditions. This first population-based study in Naryn stresses
      the need to prioritize cardiovascular and rheumatological care in these
      mountainous conditions.

PMID- 28742398
TI  - Construct validity of the UCSD performance-based skills assessment-brief version
      (UPSA-B) in HIV disease.
AB  - Among individuals living with HIV disease, approximately 60% experience problems
      with everyday functioning. The present study investigated the utility of the UCSD
      Performance-based Skills Assessment-Brief Version (UPSA-B) as a measure of
      functional capacity in HIV. We utilized a cross-sectional three-group design
      comparing individuals with HIV- associated neurocognitive disorder (HAND) (HIV +
      HAND+; n = 27), HIV+ neurocognitively normal individuals (HIV + HAND-; n = 51),
      and an HIV- comparison group (HIV-; n = 28) with broadly comparable demographics
      and non-HIV comorbidities. Participants were administered the UPSA-B, the
      Medication Management Test-Revised (MMT-R), and were assessed for manifest
      everyday functioning and quality of life, as part of a standardized clinical
      neurocognitive research battery. Results indicated that the HIV + HAND+ group had
      significantly lower UPSA-B scores than the HIV + HAND-group, but did not differ
      from the HIV- group. Among HIV+ individuals, UPSA-B scores were significantly
      related to MMT-R scores, all neurocognitive domains assessed, and education, but
      the UPSA-B was not related to manifest everyday functioning (e.g., unemployment),
      health-related quality of life, or HIV disease variables. Findings provide mixed
      support for the construct validity of the UPSA-B in HIV. Individuals impaired on
      the UPSA-B may be at increased risk for HAND, but the extent to which it detects
      general manifest everyday functioning problems is uncertain.

PMID- 28742399
TI  - Nutrition and Cancer: An Historical Perspective.-The Past, Present, and Future of
      Nutrition and Cancer. Part 2. Misunderstanding and Ignoring Nutrition.
AB  - The role that nutrition plays in cancer development and treatment has received
      considerable attention in recent decades, but it still engenders considerable
      controversy. Within the cancer research and especially the clinical community,
      for example, nutritional factors are considered to play, at best, a secondary
      role. The role of nutrition in cancer development was noted by authorities as far
      back as the early 1800s, generally under the theory that cancer is
      "constitutional" in its origin, implying a complex, multifactorial, multistage
      etiology. Opponents of this idea insisted, rather vigorously, that cancer is a
      local unifactorial disease, best treated through surgery, with little attention
      paid to the etiology and possible prevention of cancer. This "local" theory,
      developed during the late 1700s and early 1800s, gradually included, in the late
      1800s and early 1900s, chemotherapy and radiotherapy as treatment modalities,
      which now remain, along with surgery, as the basis of present-day cancer
      treatment. This highly reductionist paradigm left in its wake unfortunate
      consequences for the present day, which is the subject of this perspective.

PMID- 28742400
TI  - Role of Different CD40 Polymorphisms in Graves' Disease and Hashimoto's
      Thyroiditis.
AB  - Genome-wide association studies have led to the discovery of several
      susceptibility genes related to autoimmune thyroid diseases (AITDs). However,
      controversial results have been reported regarding the role of single-nucleotide
      polymorphism (SNP) of CD40 in the disease susceptibility. The objective of this
      study was to identify the relationship of the polymorphisms of three sites of
      CD40 with the susceptibility to AITD in the Chinese population. We genotyped
      three polymorphisms of CD40: C/T -1 SNP, 58038T site of the third exon and
      C64610G site of the ninth exon in 196 GD cases, 121 HT cases and 122 control
      subjects. The three putative polymorphism sites were amplified by PCR for
      sequencing and analysis. The genotype frequencies of CD40 -1 C/C genotype and C
      allele were significantly higher in the GD group than those in normal control.
      For the C64610G polymorphism, the C/G genotype was significantly more frequent in
      HT group than in control group, and the G allele frequencies in the GD and HT
      group were both higher than those in control group. These results indicated that
      there exist different susceptibility loci for AITD within CD40, each contributing
      a different effect in the onset and development of AITDs.

PMID- 28742401
TI  - Chikungunya Virus Seroprevalence and Associated Factors among Hospital Attendees
      in Two States of Southwest Nigeria: A Preliminary Assessment.
AB  - : Chikungunya virus (CHIKV) is a re-emerging pathogen causing long-term
      polyarthritis and encephalitis. In conducting a preliminary investigation, we
      hypothesized that there is no serologic evidence of CHIKV infection among
      attendees of selected hospitals in Lagos and Osun States, Nigeria. Sera from 304
      consecutively selected participants were screened for CHIKV IgG and IgM using
      ELISA. Findings were analyzed vis-a-vis participants' demographic and clinical
      data. Over 90.0% of the participants had never heard of CHIKV despite the fact
      that a large proportion of them (88.8%) had secondary/tertiary education.
      Overall, 41.8% were positive for, at least, one antibody type (IgG or IgM), while
      about 16.0% of the participants had dual seropositivity (CHIKV IgG and IgM) with
      gender as associated factor (odds ratio [OR]: 2.8, p = 0.03). Prevalence rates
      were 31.8% and 38.4% for CHIKV IgG and IgM, respectively. Only hospital location
      (Osogbo) was associated with CHIKV IgG (OR: 2.2, p = 0.009), while gender alone
      was associated with CHIKV IgM (OR: 3.0, p = 0.001). Participants seropositive for
      CHIKV antibodies were mostly adults (18-59 yrs) belonging to the active work
      force; five (22.7%) and three (20.0%) of the pregnant participants had CHIKV IgG
      and IgM, respectively. Detection of CHIKV IgM in some participants might make
      them potentially infectious to the newborn and mosquito vectors. Importantly,
      participants positive for either IgG or IgM had fever (72.8%, 67.2%) and general
      body pains (61.7%, 57.6%), respectively. This ELISA-based study revealed
      serologic evidence of CHIKV infection among hospital attendees in Lagos and Osun
      states with the group-specific prevalence rates being considerably high.
      ABBREVIATIONS: Chikungunya virus (CHIKV); Chikungunya (CHIK); enzyme-linked
      immunosorbent assay (ELISA); immunoglobulin G or M (IgG/IgM); odds ratio (OR);
      non-structural proteins (nsP); hemagglutination inhibiting (HI); complement
      fixing (CF); neutralization test (NT); immunofluorescence assay (IFA); plaque
      reduction neutralization test (PRNT); confidence interval (CI); analysis of
      variance (ANOVA); body temperature (BT); Building Nigeria's Response to Climate
      Change (BNRCC).

PMID- 28742402
TI  - Association of IL-10-Regulating MicroRNAs in Peripheral Blood Mononuclear Cells
      with the Pathogenesis of Autoimmune Thyroid Disease.
AB  - Interleukin (IL)-10 is known to suppress inflammation in autoimmune diseases. IL
      10 can be regulated by miRNAs. To elucidate the involvement of miRNAs that
      regulate IL-10 expression with the pathogenesis of autoimmune thyroid disease
      (AITD), we examined the expression levels of hsa-miR-27a-3p, hsa-miR-98-5p, hsa
      miR-106a-5p, and hsa-miR-223-3p in peripheral blood mononuclear cells (PBMCs)
      from 43 patients with Graves' disease (GD), 38 patients with Hashimoto's disease
      (HD), and 21 healthy volunteers. We evaluated the association between the
      expression levels of four miRNAs and intracellular expression of IL-10 in PBMCs
      from 11 healthy volunteers. We also genotyped MIR27A rs895819 G/A and MIR106A
      rs3747440 C/G polymorphisms, which may be related to the expression of these
      miRNAs in 141 patients with GD, 178 patients with HD, and 84 healthy volunteers.
      The expression level of hsa-miR-106a-5p was significantly higher in patients with
      intractable GD than in those with GD in remission (p = 0.0113). The expression
      level of hsa-miR-223-3p was significantly lower in GD than in HD and lower in
      patients with intractable GD than in healthy volunteers (p = 0.0094, 0.0340). We
      found a negative correlation between the expression levels of hsa-miR-98-5p and
      the proportions of IL-10+ cells in stimulated PBMCs from healthy volunteers (p =
      0.0092). The G allele of the MIR27A polymorphism was significantly more frequent
      in patients with mild HD than in healthy volunteers (p = 0.0432). In conclusion,
      the expression levels of hsa-miR-106a-5p and hsa-miR-223-3p were associated with
      the pathogenesis of AITDs. hsa-miR-98-5p may negatively regulate the expression
      of IL-10. The functional polymorphism of MIR27A was associated with HD severity.

PMID- 28742403
TI  - LpxC inhibitors: a patent review (2010-2016).
AB  - INTRODUCTION: The Zn2+-dependent deacetylase LpxC is an essential enzyme of lipid
      A biosynthesis in Gram-negative bacteria and a promising target for the
      development of antibiotics selectively combating Gram-negative pathogens.
      Researchers from industry and academia have synthesized structurally diverse LpxC
      inhibitors, exhibiting different LpxC inhibitory and antibacterial activities.
      Areas covered: A brief introduction into the structure and function of LpxC,
      showing its suitability as antibacterial target, along with the structures of
      several reported LpxC inhibitors, is given. The article reviews patents (reported
      between 2010 and 2016) and related research publications on novel small-molecule
      LpxC inhibitors. Emphasis is placed on structure-activity relationships within
      the reported series of LpxC inhibitors. Expert opinion: The performed analysis of
      patents revealed that the current search for novel LpxC inhibitors is focused on
      small molecules, sharing common structural features like a Zn2+-chelating group
      as well as a highly lipophilic side-chain. However, despite the promising
      preclinical data of many of the reported compounds, besides the recently
      withdrawn clinical candidate ACHN-975, no other LpxC inhibitor has entered
      clinical trials. The lack of clinical candidates might be related with undesired
      effects caused by the common structural elements of the LpxC inhibitors.

PMID- 28742404
TI  - Pregnane X Receptor Polymorphisms and Risk of Inflammatory Bowel Disease: A Meta
      Analysis.
AB  - BACKGROUND: Pregnane X receptor (PXR) gene polymorphisms have been widely studied
      in terms of the association with inflammatory bowel disease (IBD), with
      inconsistent results. OBJECTIVE: The present meta-analysis was performed to
      assess the association between PXR gene polymorphisms and the susceptibility of
      IBD, Crohn's disease (CD), and ulcerative colitis (UC). METHODS: PubMed, Wanfang,
      and CNKI databases were searched for eligible studies before November 1, 2016.
      Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to
      calculate the various genetic models using either a fixed-effect or a random
      effect model. The heterogeneity of the included studies was examined with Cochran
      Q and I2 statistics. Begg's rank correlation test and Egger's linear regression
      test were used to assess the publication bias. RESULTS: A total of six studies
      with 4248 cases and 3853 controls were included in this meta-analysis. Three PXR
      gene polymorphisms were evaluated: rs1523127, rs2276707, and rs6785049. Our
      analyses of rs1523127, rs2276707, and rs6785049 suggested that PXR gene
      polymorphism had no obvious influence on the risk of IBD in Caucasians. Subgroup
      analyses based on disease type showed similar results. CONCLUSION: Our meta
      analysis revealed that PXR gene polymorphism may not be significantly associated
      with IBD susceptibility. However, the number of original studies was limited and
      further studies with large samples are needed to verify the results.
      ABBREVIATIONS: PXR = pregnane X receptor, IBD = inflammatory bowel disease, CD =
      Crohn's disease, UC = ulcerative colitis, ORs = pooled odds ratios, 95% CIs = 95%
      confidence intervals, NOS = Newcastle-Ottawa scale, HWE = Hardy-Weinberg
      equilibrium.

PMID- 28742405
TI  - True Dopers or Negligent Athletes? An Analysis of Anti-Doping Rule Violations
      Reported to the World Anti-Doping Agency 2010-2012.
AB  - BACKGROUND: The sanction that an athlete receives when an anti-doping rule
      violation has been committed depends on the specific circumstances of the case.
      Anti-doping tribunals decide on the final sanction, following the rules of the
      World Anti-Doping Code. OBJECTIVES: To assess the athletes' degree of fault based
      on the length of sanctions imposed on them to feed policy-related discussions.
      METHODS: Analysing data from the results management database of the World Anti
      Doping Agency for anonymous information of anti-doping rule violations in eight
      selected sports covering the years 2010-2012. RESULTS: Four out of ten athletes
      who committed an anti-doping rule violation received a suspension that was lower
      than the standard. This is an indication that tribunals in many instances are not
      convinced that the athletes concerned were completely at fault, that mitigating
      circumstances were applicable, or that full responsibility of the suspected
      violation should not be held against them. Anabolic agents, peptide hormones, and
      hormone modulators lead to higher sanctions, as do combinations of several anti
      doping rule violations. CONCLUSIONS: This first analysis of information from the
      World Anti-Doping Agency's results management database indicates that a large
      proportion of the athletes who commit anti-doping rule violations may have done
      this unintentionally. Anti-doping professionals should strive to improve this
      situation in various ways.

PMID- 28742406
TI  - The efficacy of low-dose tadalafil in patients undergoing hemodialysis with end
      stage renal disease.
AB  - BACKGROUND: Erectile dysfunction (ED) is a disorder that is frequently observed
      in people with chronic kidney disease who undergo hemodialysis (HD). In the
      context of evidence-based medicine, we aimed to investigate the effect of low
      dose tadalafil on sexual function in patients undergoing HD. METHODS: The medical
      records of 30 males (aged 29-65 years) with end-stage renal disease (ESRD) on a
      HD program, and who had received 5 mg tadalafil twice weekly, were
      retrospectively evaluated. Changes in erectile and ejaculatory function were
      evaluated using the International Erectile Function Index questionnaire, the
      Erection Hardness Scale (EHS), and the Male Sexual Health Questionnaire (MSHQ).
      RESULTS: The mean age of the patients was 47.6 +/- 10.1 years, their mean body
      mass index was 24.3 +/- 4.2 kg/m2, their mean hemoglobin was 11.9 +/- 0.9 g/dL,
      and their mean creatinine clearance was 5.8 +/- 1.1 mL/min. At the third month of
      treatment, 36.6% of the patients had no ED, 40% had mild ED, 10% had mild-to
      moderate ED, and 13.3% had moderate ED. The mean MSHQ scores (p < .05) and the
      mean EHS scores (p = .001) were significantly improved. There was no significant
      difference between Beck's Depression Inventory scores (p > .05), but Hamilton
      anxiety rate scores decreased significantly (p = .001). The quality-of-life score
      improved throughout the study period (p < .05). CONCLUSIONS: Tadalafil therapy is
      an effective therapeutic option in patients with ESRD who undergo HD, not only
      for the treatment of ED, but also for ejaculatory function, with acceptable
      adverse effects.

PMID- 28742407
TI  - TLR5 Polymorphisms rs2072493, rs5744174, and rs5744168 Are Not Genetic Risk
      Factors for Chronic Helicobacter pylori Infection in Indian Tamils.
AB  - The incidence of Helicobacter pylori (H. pylori) infection and gastric cancer is
      on the rise in India, and the genetic factors influencing the increased
      susceptibility in Indian population remain obscure. Toll-like receptors (TLRs)
      play a major role in innate immune system and genetic polymorphisms affecting
      their function were reported to enhance the risk for H. pylori infection. Seventy
      seven patients (n = 77) diagnosed with H. pylori infection and 230 healthy
      subjects were recruited in this study. The rs2072493, rs5744174, and rs5744168
      polymorphisms within TLR5 gene were genotyped using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and Tetra-ARMS PCR genotyping
      techniques. Present study revealed that these studied polymorphisms are less
      frequent in south Indian Tamils and thus failed to confer a significant risk to
      develop chronic H. pylori infections. The distribution of ancestral allele of
      rs2072493 polymorphism conferred resistance to develop chronic H. pylori
      infection in our population (p = 0.024; OR  =  0.53; 95% CI: 0.3-0.91). The
      lesser incidence of polymorphic alleles suggests that the TLR5 gene is under
      genetic selection pressure to withstand the prevailing endemic infections among
      south Indian Tamils.

PMID- 28742408
TI  - Risk Competence in Dealing With Alcohol and Other Drugs in Adolescence.
AB  - BACKGROUND: Adolescence is a critical phase for the development substance use
      patterns. We propose that individual competence in dealing with psychoactive
      substances is crucial for the development of healthy substance use behavior and
      prevention of substance misuse or addiction. OBJECTIVES: We present a new concept
      of health related skills in dealing with alcohol and other drugs in adolescence,
      its operationalization and validation. Our conception of risk competence (RICO)
      consists of the four major factors being Reflective, Informed, Self-Controlled
      and Life-Oriented, and their sub-facets. METHODS: Based on a sample of N = 753
      adolescents we used classical test theory as well as item response theory to
      create a new measure of RICO. Validity was investigated in a new sample of N =
      229 with regard to substance use, risk perception, and measures of personality
      (Big Five, sense of coherence, general self-efficacy). RESULTS: RICO contains 7
      scales with 28 items that measure independent aspects of risk competence. Cross
      sectional criterion validity for most of the scales could be shown.
      Conclusions/Importance: The new RICO scales are a valid measure of different
      aspects of risk competence in dealing with psychoactive substances. The
      questionnaire can be used in general research settings, but may also be applied
      to assess the effects of interventions.

PMID- 28742409
TI  - The effects of vitamin D and evening primrose oil co-supplementation on lipid
      profiles and biomarkers of oxidative stress in vitamin D-deficient women with
      polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.
AB  - PURPOSE OF THE STUDY: There was inconsistent evidence about the benefit of
      vitamin D plus evening primrose oil (EPO) supplement intake on lipid profiles and
      reduced oxidative stress among women with polycystic ovary syndrome (PCOS). The
      current study was performed to evaluate the effects of vitamin D plus EPO
      supplementation on lipid profiles and biomarkers of oxidative stress in vitamin D
      deficient women with PCOS. MATERIALS AND METHODS: This randomized, double-blind,
      placebo-controlled trial was performed among 60 vitamin D-deficient women with
      PCOS. Participants were randomly assigned into two groups to receive either 1000
      IU vitamin D3 plus 1000 mg EPO (n = 30) or placebo (n = 30) for 12 weeks.
      Metabolic profiles were quantified at baseline and after the 12-week
      intervention. RESULTS: Compared with the placebo group, women in vitamin D and
      EPO co-supplementation group had significant increases in serum 25-hydroxyvitamin
      D (25(OH)D) (+10.7 +/- 8.4 vs. -0.5 +/- 1.6 ng/mL, p < 0.001) and plasma total
      glutathione (GSH) (+62.7 +/- 58.0 vs. -0.7 +/- 122.7 umol/L, p = 0.01), while
      there were significant decreases in triglycerides (-7.3 +/- 23.8 vs. +6.9 +/-
      26.3 mg/dL, p = 0.03), very low-density lipoprotein (VLDL) cholesterol levels (
      1.5 +/- 4.7 vs. +1.4 +/- 5.3 mg/dL, p = 0.03), total/high-density lipoprotein
      cholesterol ratio (-0.3 +/- 0.4 vs. -0.02 +/- 0.4, p = 0.02), and malondialdehyde
      (MDA) concentration (-0.4 +/- 0.4 vs. +0.5 +/- 1.8 umol/L, p = 0.008).
      CONCLUSION: Overall, vitamin D and EPO co-supplementation for 12 weeks among
      vitamin D-deficient women with PCOS significantly improved triglycerides, VLDL
      cholesterol, GSH, and MDA levels.

PMID- 28742410
TI  - Content Analysis of Advantages and Disadvantages of Drinking Among Individuals
      With the Lived Experience of Homelessness and Alcohol Use Disorders.
AB  - BACKGROUND: Alcohol use disorders (AUDs) are more prevalent among people who are
      homeless than in the general population. Thus, homeless individuals experience
      disproportionately high levels of alcohol-related problems and associated
      publicly funded criminal justice and healthcare system utilization. Available
      treatment services, however, are not effective at engaging and treating this
      population. To better tailor treatment services to their needs, it is imperative
      we understand this population's perceptions of their alcohol use. OBJECTIVES: The
      aim of this study was to provide description and relative rankings of the
      advantages and disadvantages of alcohol use from this population's perspectives.
      METHODS: Participants were 44 individuals with lived experiences of AUDs and
      homelessness who received services at community-based agencies in Seattle,
      Washington. Open-ended prompts were used in interviews conducted in 2013-2014 to
      assess the perceived role of alcohol in participants' lives, including
      participants' perceptions of the advantages and disadvantages of their current
      drinking, and a conventional content analysis was conducted. RESULTS: The most
      frequently mentioned advantages of drinking included positively and negatively
      reinforcing psychological reasons, perceived control over drinking, and social
      benefits. Physical effects, concerns about dependence on alcohol, and health
      problems were the most commonly mentioned disadvantages. Conclusions/importance:
      By documenting the perceived advantages and disadvantages of drinking among
      people with the lived experience of homelessness and AUDs, this study supplies
      information providers may use to better tailor treatment services to this
      multimorbid, high service-utilizing population's needs and interests.

PMID- 28742411
TI  - Is Major Depression Linked to Alcohol-Impaired Driving?
AB  - BACKGROUND: Alcohol-impaired driving causes a substantial proportion of motor
      vehicle accidents. Depression is a prevalent psychiatric disorder among drinker
      drivers. Few previous studies have investigated the relationship between major
      depression and alcohol-impaired driving. OBJECTIVES: We investigated whether
      depression has a positive relationship with the probability of alcohol-impaired
      driving after controlling for the co-occurrence of binge drinking and alcohol
      dependence. METHODS: Our data consisted of drinkers aged 21-64 years from two
      waves of the National Epidemiologic Survey of Alcohol and Related Conditions.
      Cross-sectional analysis investigated whether depression is an independent risk
      factor for drinking-driving. Longitudinal analysis distinguished the relationship
      of depression onset, continuance, and recovery with changes in drinking-driving
      behaviors between the waves. These dual approaches allowed comparisons with
      previous studies. RESULTS: Major depression was a small but statistically
      significant predictor of changes in alcohol-impaired driving behaviors among
      males but not females. Binge drinking and alcohol dependence were comparatively
      stronger predictors. Conclusions/Importance: There is limited empirical support
      that treating depression reduces drinking and driving in males who do not exhibit
      symptoms of alcohol use disorders. For persons with co-occurring depression and
      alcohol use disorders, depression treatment should be part of a strategy for
      treating alcohol use disorders which are highly related to drinking and driving.

PMID- 28742412
TI  - Post-High School Changes in Tobacco and Cannabis Use in the United States.
AB  - BACKGROUND: The transition from high school into young adulthood is a critical
      developmental period with many young people going to college, moving residence,
      and entering the work force for the first time. The NEXT Generation Health Study
      (NEXT) is a nationally representative longitudinal study of adolescent health
      behaviors. Previous NEXT research has found that the post-high school environment
      is associated with changes in alcohol use. OBJECTIVES: The current study
      investigated the impact of school status, residential status, and work status on
      cannabis and cigarette use among post-high school participants. RESULTS: Living
      in a dorm/fraternity/sorority was associated with an increased prevalence in
      cannabis use while attending a 4-year college was associated with a decreased
      prevalence in cigarette use. CONCLUSIONS: Some aspects of the post-high school
      environment are related to cannabis and cigarette use. Differences in the social
      circumstances of cigarette and cannabis use and recent campaigns in colleges to
      reduce smoking may explain some of these trends.

PMID- 28742413
TI  - Association of Current and Lifetime DSM-IV Drug use Disorder Diagnoses to 6-Month
      Changes in Smoking Behavior in Risky Drinking Smokers: A Pilot Study.
AB  - BACKGROUND: Alcohol and other drug use disorders co-occur with cigarette smoking
      and negatively impact cessation outcomes. OBJECTIVES: This study examined the
      differential effects of current and lifetime DSM-IV drug diagnoses on the 6-month
      smoking outcomes of 84 untreated heavy drinking smokers who were motivated to
      quit smoking in the next 6-months. METHODS: Generalized estimating equations
      (GEE) assessed changes in nicotine dependence, readiness to quit smoking, and
      prevalence of heavy smoking from baseline to 6-months as a function of time,
      baseline drinking severity, and drug diagnosis. RESULTS: GEE models showed that
      nicotine dependence and prevalence of heavy smoking decreased over 6-months,
      irrespective of drug diagnosis and baseline alcohol consumption. Several 3-way
      interactions were found, showing differences in the rate of change over time in
      readiness to quit smoking and prevalence of heavy smoking as a function of
      current versus lifetime drug diagnosis and higher versus lower of baseline
      alcohol consumption. Conclusions/Importance: Drug diagnoses are common in risky
      drinking smokers, and significantly impede changes in smoking behavior and
      motivation to quit. Treatment planning for smoking cessation should include a
      thorough assessment of current and past drug use behavior to determine the impact
      on readiness to quit and quit success. Mechanisms of change in smokers with
      multiple substance use diagnoses should be examined.

PMID- 28742414
TI  - Neural Correlates of Depressive Symptoms in Smokers - A Systematic Review of
      Imaging Studies.
AB  - This review aims to summarize neuroimaging studies in order to better understand
      the neural correlates of depressive symptoms in tobacco smokers. Using the
      keywords "depressive OR depression" AND "tobacco OR nicotine OR smok* OR
      cigarette" AND "neuroimage OR magnetic resonance OR smri OR structural magnetic
      resonance OR fmri OR functional magnetic resonance OR pet OR positron emission
      tomography", literature search was conducted in PubMed, Web of Science and
      PsycINFO databases. The first and the last author read the abstracts of all the
      studies found in the search (n = 179). The inclusion and exclusion criteria were
      applied and 150 articles were excluded. Then, both authors assessed the remaining
      29 studies for eligibility and 16 studies were included in the present review. In
      the phase of active/chronic smoking, depressive symptoms are characterized as
      comorbidity related to an enhancement of dopamine release, and smokers have
      decreased Monoamine oxidase A (MAO-A). Stimuli-related functional magnetic
      resonance imaging (Stimuli-fMRI) studies also show that there is a positive
      correlation between the level of depressive symptoms and a greater response to
      general negative stimuli in active/chronic smokers. In the withdrawal phase,
      depressive symptoms are related to the withdrawal syndrome and increased MAO-A.
      Stimuli-fMRI studies show that there is a negative correlation between level of
      depressive symptoms and reactivity to negative stimuli in recent abstinent
      smokers. Major areas of the reward system such as the striatum and areas related
      to impulse control are activated to a greater extent in depressive smokers
      compared to non-depressed smokers.

PMID- 28742415
TI  - Air- and Dust-Borne Fungi in Indoor and Outdoor Home of Allergic Patients in a
      Dust-Storm-Affected Area.
AB  - Despite the recent increases in fungi-induced allergic diseases, there is no
      report yet in the region of the Persian Gulf on concentration levels of fungi in
      relationship with health state. Therefore, our aim was to measure fungi
      prevalence as well as to evaluate the relationships between air- and dust-borne
      fungal genera and allergic diseases. A matched case-control study was carried out
      including 45 allergic cases and 45 age- and gender-matched controls for each
      individual. Indoor and outdoor dust and indoor air samples were collected from
      participant homes during May to October 2015. A Quick Take 30 Pump and sterile
      wet swab were used to determine fungal types and their amounts in the air
      (CFU/m3) and dust (CFU/100 cm2) samples, respectively. A significant reverse
      association was found between indoor dust-borne Alternaria and asthma (Odds ratio
      (OR) = 0.14, 95% CI = 0.02-0.86). Contrarily, increased levels of indoor air
      borne Aspegillus fumigatus (OR = 2.00, 95% CI = 0.37-10.55) and Alternaria (OR =
      3.00, 95% CI = 0.34-25.83) were correlated with asthma development. Also,
      correlation analysis showed a significant relation between indoor air-borne
      Penicillium levels and reactivity to skin prick test in asthmatic patients (p =
      0.04). Our findings support the notion that fungal exposures can either cause or
      prevent the development of allergic diseases. Accordingly, appropriate measures
      should be taken for a better management of fungi-induced allergic diseases.

PMID- 28742416
TI  - Comparisons of Alcohol and Drug Dependence in Terms of Attachments and Clinical
      Issues.
AB  - BACKGROUND: Alcohol and drug dependencies are associated with different social
      stigmas, and some studies suggest they might exhibit different clinical
      presentations. Further, the treatments for each vary considerably. Alcohol versus
      drug use problems were compared in terms of attachment patterns and related
      clinical treatment issues in two interlocking studies using converging logic and
      designs. METHODS: In Study 1, alcohol versus drug dependence was defined in terms
      of a known groups design. Patients from an inpatient alcohol treatment center,
      patients receiving treatment for opiate dependence in a methadone maintenance
      clinic, and controls were compared on the 29 scales of the Attachment and
      Clinical Issues Questionnaire (ACIQ). Study 2 sampled a substantially different
      population (491 university students) and used different operational definitions
      of substance use problems, relying on screening instruments. RESULTS: Study 1
      found that, although the drug and alcohol dependent patients differed
      substantially from the controls, they did not differ from one another on any of
      the 29 ACIQ scales measuring attachments and clinical issues. Study 2 converged
      on the known groups design of Study 1, showing convergent and concurrent rather
      than discriminate evidence for the alcohol and drug dependence screening
      instruments. CONCLUSION: Alcohol and drug dependencies were not found to differ
      significantly in terms of attachments or clinical issues. These studies aimed to
      provide clearer and more empirically grounded guidance to the clinician and
      researcher.

PMID- 28742417
TI  - MICA-129Met/Val Polymorphism Is Associated with Early-Onset Breast Cancer Risk.
AB  - The major histocompatibility complex class I-related chain A (MICA), expressed on
      cell surface, plays an important role in the elimination of both virus-infected
      cells and tumor through the activation of the natural killer (NK) receptor NKG2D.
      A polymorphic change from methionine (Met) to valine (Val) at amino acid position
      129 categorizes MICA alleles into strong and weak binders for the NKG2D receptor
      and has been found in a variety of immune-related disorders. In this study, we
      investigated the potential interaction between genetic polymorphism of MICA and
      the development of breast cancer. We recruited 192 unrelated Tunisian women
      affected by breast cancer and 205 controls age-matched women, all genotyped for
      MICA-129 Met/Val (rs 1051792). A significant association was found between the
      Val allele and Val/Val genotype and the risk of breast cancer (p = 0.002, OR =
      1.64, 95% CI = [1.17-2.27]; p = 0.002, OR = 1.88, 95% CI = [1.24-2.87],
      respectively). After stratification with clinical-pathology parameters, we found
      that 71% of women aged lower than 40 years had a Val/Val genotype versus 49% (p =
      0.014). About 72% of these patients having a family history of cancers had a
      Val/Val genotype (p = 0.04). These results suggest that tumor escape mechanism
      because of failure in order to activate NK cells by MICA-129 Val allele may play
      a role in individual susceptibility for breast cancer development in Tunisian
      women.

PMID- 28742418
TI  - Health Risk Behavior Among Justice Involved Male and Female Youth: Exploratory,
      Multi-Group Latent Class Analysis.
AB  - BACKGROUND: Youth involved in the juvenile justice system experience a
      disproportionate prevalence of serious mental health issues, substance abuse, and
      are at an increased risk of engaging in risky sexual practices. Gender
      differences exist, with girls at a markedly greater risk of acquiring a sexually
      transmitted disease. OBJECTIVES: The present study seeks to determine if there
      are subgroups of male and female youth who differ in their health risk behavior.
      If so, do any male or female subgroups at different levels of health risk differ
      in regard to their sociodemographic and psychological factors, and finally, what
      are intervention/service delivery implications of these differences. METHODS:
      Youth were participants in an innovative health service at a centralized intake
      facility located in a large southeastern U.S. city. Latent class analysis and
      multinomial logistic regression is utilized to examine the heterogeneity of
      health risk behaviors across gender groups in a sample of 777 newly arrested
      youth. RESULTS: Results indicate a three class solution provided the optimal fit
      with the data for each gender group: a Lower Health Risk group, a Higher Health
      Risk group, and a Highest Health Risk group. Multinomial logistic regression
      analysis identified significant sociodemographic and depression effects among
      both male and female youth. Conclusions/Importance: Youth characterized by risky
      sexually behavior, elevated depression, and drug involvement should be the focus
      of integrated intervention services. This study documents the critical need for
      front end, juvenile justice intake facilities to provide behavioral and public
      health screening, with treatment follow-up, on newly arrested youth.

PMID- 28742419
TI  - Insights into the management of chronic myeloid leukemia in resource-poor
      settings: a Mexican perspective.
AB  - INTRODUCTION: The arrival of targeted therapy for chronic myeloid leukemia (CML)
      was revolutionary. However, due to the high cost of tyrosine kinase inhibitors,
      access to this highly effective therapy with strict monitoring strategies is
      limited in low to middle-income countries. In this context, following standard
      recommendations proposed by experts in developed countries is difficult. Areas
      covered: This review aims to provide an insight into the management of patients
      with CML living in a resource-limited setting. It addresses several issues:
      diagnosis, initial treatment, disease monitoring, and additional treatment
      alternatives including allogeneic hematopoietic stem cell transplantation. Expert
      commentary: Imatinib is probably the most cost-effective TKI for initial
      treatment in developing and underdeveloped countries. Generic imatinib
      preparations should be evaluated before considering their widespread use.
      Adherence to treatment should be emphasized. Adequate monitoring can be performed
      through several methods successfully and is important for predicting outcomes,
      particularly early in the first year, and if treatment suspension is being
      considered. Access to further therapeutic alternatives should define our actions
      after failure or intolerance to imatinib, preferring additional TKIs if possible.
      Allogeneic transplantation in chronic phase is a viable option in this context.

PMID- 28742420
TI  - Orthodontics with Customized versus Noncustomized Appliances: A Randomized
      Controlled Clinical Trial.
AB  - This randomized controlled trial aimed to evaluate the duration and outcome
      quality of orthodontic treatment with a customized fixed appliance system versus
      a noncustomized system. Patients ( n = 180) were randomized and received
      orthodontic treatment with the Insignia customized orthodontic system or the
      Damon Q noncustomized orthodontic system. The allocation sequence was concealed
      using identical, sequentially numbered, opaque, sealed envelopes. Patients with
      nonextraction treatment plans were treated by 2 equally experienced
      orthodontists. Pretreatment and posttreatment plaster casts were made for each
      patient, and the models were rated using the Peer Assessment Rating (PAR) score.
      Planning time, treatment duration, and numbers of loose brackets, visits, and
      complaints were recorded. The examined null hypothesis was that the customized
      appliance system was not associated with significantly ( P < 0.05) shorter
      treatment duration compared to a noncustomized appliance. We analyzed 85 patients
      in the customized group and 89 in the noncustomized group. Treatment duration was
      1.29 +/- 0.35 y in the customized group and 1.24 +/- 0.37 y in the noncustomized
      group. In the customized group, the PAR score was 23.32 +/- 9.15 pretreatment and
      5.38 +/- 3.75 posttreatment. In the noncustomized group, the PAR score was 21.84
      +/- 7.95 pretreatment and 5.93 +/- 3.58 posttreatment. None of these outcomes
      significantly differed between groups. On the other hand, the orthodontist had a
      significant effect on treatment duration, quality of treatment outcome, and
      number of visits ( P < 0.05). A higher PAR score pretreatment was associated with
      increased treatment duration, posttreatment PAR, and number of visits ( P <
      0.05). Compared to the noncustomized group, the customized group had more loose
      brackets, a longer planning time, and more complaints ( P < 0.05). The customized
      orthodontic system was not associated with significantly reduced treatment
      duration, and treatment quality was comparable between the 2 systems (
      ClinicalTrials.gov : NCT01268852).

PMID- 28742421
TI  - Comparison of 30 mCi and 50 mCi I-131 doses for ablation of thyroid remnant in
      papillary thyroid cancer patients.
AB  - PURPOSE OF THE STUDY: To compare efficacy of thyroid remnant ablation using 30
      mCi or 50 mCi 131-I in papillary thyroid cancer patients. MATERIALS AND METHODS:
      Five hundred and fifteen consecutive patients with Tumor-Node-Metastasis (TNM)
      stages T1-T3 N1/N0/NX receiving either 30 mCi or 50 mCi I-131 were analyzed for
      the effectiveness of remnant ablation using rhTSH-stimulated serum thyroglobulin.
      One hundred and five consecutive patients receiving 100 mCi I-131 were analyzed
      for the incidence of radiation thyroiditis and sialadenitis. RESULTS AND
      CONCLUSIONS: Doses of 30 mCi and 50 mCi were equally effective for low- and
      moderate-risk disease but 30 mCi was less effective for T1T2NX disease, and 50
      mCi was less effective for T3 compared to T1T2 disease. Low dose radiation
      hypersensitivity or unknown more extensive disease may have accounted for
      observed differences. Radiation thyroiditis and sialadenitis were more common in
      a comparison series of 100 mCi dose compared to 30 mCi, but not more common than
      in 50 mCi doses.

PMID- 28742422
TI  - VIRUS ISOLATION AND MOLECULAR DETECTION OF BLUETONGUE AND EPIZOOTIC HEMORRHAGIC
      DISEASE VIRUSES FROM NATURALLY INFECTED WHITE-TAILED DEER (ODOCOILEUS
      VIRGINIANUS).
AB  - Hemorrhagic disease in North America is caused by multiple serotypes of epizootic
      hemorrhagic disease virus (EHDV) and bluetongue virus (BTV). Diagnostic tests for
      detection of EHDV and BTV include virus isolation (VI), reverse transcriptase
      (RT)-PCR, and real-time RT-PCR (rRT-PCR). Our objective was to compare the
      diagnostic capabilities of three rRT-PCR protocols for detection of EHDV and BTV
      from naturally infected white-tailed deer (Odocoileus virginianus). We compared
      the effectiveness of these assays to traditional viral detection methods (e.g.,
      VI) for historic and current clinical cases. Because of the variable nature of
      tissue collection and storage before diagnostic testing, an evaluation of viral
      persistence on multiple freeze-thaw events was also conducted. Two of the rRT-PCR
      assays provided for reliable detection of EHDV and BTV from 100% of clinically
      affected and VI-confirmed infected animals. Additionally, no significant change
      in viral titer was observed on multiple freeze-thaw events.

PMID- 28742423
TI  - Chemical Immobilization of Free-ranging Yellow Armadillos (Euphractus sexcinctus)
      for Implantation of Intra-abdominal Transmitters.
AB  - Free-ranging yellow armadillos (Euphractus sexcinctus) from the Brazilian
      Pantanal were captured for surgical implantation of intra-abdominal radio
      transmitters. During March 2014, 11 animals were chemically immobilized with a
      combination of intramuscular ketamine hydrochloride, xylazine hydrochloride,
      midazolam maleate, and atropine sulfate. The mean induction time and initial
      heart rate in males was higher than in females. The sex of armadillos did not
      affect the respiratory rate, which increased from the beginning to end of the
      monitoring time. The rectal temperatures of females remained almost unchanged,
      whereas the rectal temperatures of males suffered a slight drop through the
      procedure. The mean (+/-SD) total surgical time was 50+/-6.5 min, and the total
      anesthetic recovery time was 2.5+/-0.5 h. The armadillos were monitored for 24 h
      after surgery and released at their capture site. The anesthetic association was
      effective, promoting muscle relaxation and analgesia that allowed the performance
      of surgical procedures.

PMID- 28742424
TI  - Evaluation of Noise Exposure Secondary to Wind Noise in Cyclists.
AB  - Objective Determine if the noise levels of wind exposure experienced by cyclists
      reach levels that could contribute to noise-induced hearing loss. Study Design
      Industrial lab research. Setting Industrial wind tunnel. Subjects and Methods A
      commercial-grade electric wind tunnel was used to simulate different speeds
      encountered by a cyclist. A single cyclist was used during the simulation for
      audiometric measurements. Microphones attached near the ears of the cyclist were
      used to measure the sound (dB sound pressure level) experienced by the cyclist.
      Loudness levels were measured with the head positioned at 15-degree increments
      from 0 degrees to 180 degrees relative to the oncoming wind at different speeds
      (10-60 mph). Results Wind noise ranged from 84.9 dB at 10 mph and increased
      proportionally with speed to a maximum of 120.3 dB at 60 mph. The maximum of
      120.3 dB was measured at the downwind ear when the ear was 90 degrees away from
      the wind. Conclusions Wind noise experienced by a cyclist is proportional to the
      speed and the directionality of the wind current. Turbulent air flow patterns are
      observed that contribute to increased sound exposure in the downwind ear.
      Consideration of ear deflection equipment without compromising sound awareness
      for cyclists during prolonged rides is advised to avoid potential noise trauma.
      Future research is warranted and can include long-term studies including
      dosimetry measures of the sound and yearly pre- and postexposure audiograms of
      cyclists to detect if any hearing loss occurs with long-term cycling.

PMID- 28742425
TI  - Association between Hypertension and Epistaxis: Systematic Review and Meta
      analysis.
AB  - Objective Whether there is an association or a cause-and-effect relationship
      between epistaxis and hypertension is a subject of longstanding controversy. The
      objective of this systematic review and meta-analysis was to determine the
      association between epistaxis and hypertension and to verify whether hypertension
      is an independent risk factor of epistaxis. Data Sources A comprehensive search
      was performed using the MEDLINE, EMBASE, and Cochrane Library databases. Review
      Methods The review was performed according to the Meta-analysis of Observational
      Studies in Epidemiology guidelines and reported using the Preferred Reporting
      Items for Systematic Reviews and Meta-analysis guidelines. Results We screened
      2768 unique studies and selected 10 for this meta-analysis. Overall, the risk of
      epistaxis was significantly increased for patients with hypertension (odds ratio,
      1.532 [95% confidence interval (CI), 1.181-1.986]; number needed to treat, 14.9
      [95% CI, 12.3-19.0]). Results of the Q test and I2 statistics suggested
      considerable heterogeneity ([Formula: see text] = 0.038, I2 = 49.3%). The
      sensitivity analysis was performed by excluding 1 study at a time, and it
      revealed no change in statistical significance. Conclusion Although this meta
      analysis had some limitations, our study demonstrated that hypertension was
      significantly associated with the risk of epistaxis. However, since this
      association does not support a causal relationship between hypertension and
      epistaxis, further clinical trials with large patient populations will be
      required to determine the impact of hypertension on epistaxis.

PMID- 28742426
TI  - Educating Students for a Lifetime of Physical Activity: Enhancing Mindfulness,
      Motivation, and Meaning.
AB  - For many years, pedagogical scholars and physical education (PE) teachers have
      worked to enhance effective teaching and learning environments. Yet for some
      children, youth, and young adults, many of the benefits associated with a
      physically active lifestyle remain elusive. Enhancing programming and performance
      to meet physical activity goals may require moving programs beyond "effective."
      It will require teachers and program leaders to focus programmatic attention on
      strategies to actually increase students' out-of-class physical activity
      behavior. Transformative PE provides physical activity content within a nurturing
      and motivating environment that can change students' lives. It focuses on PE
      students' role in cognitive decision making, self-motivation, and their search
      for personal meaning that can add connection and relevance to physical
      activities. In this SHAPE America - Society of Health and Physical Educators
      Research Quarterly for Exercise and Sport Lecture, I have synthesized the
      research on these topics to emphasize useful findings applicable to teachers'
      everyday planning and teaching. Using sport, physical activity, dance, and
      adventure activities as the means to an end for personal and social growth, we
      can meet our commitment to effective standards-based education while preparing
      students for a lifetime of physical activity.

PMID- 28742427
TI  - A Comparison of Multimodal Analgesic Approaches in Institutional Enhanced
      Recovery After Surgery Protocols for Colorectal Surgery: Pharmacological Agents.
AB  - INTRODUCTION: Enhanced Recovery After Surgery (ERAS(r)) protocols are the
      cornerstone of improved recovery after colorectal surgery. Their implementation
      leads to reduced morbidity and shorter hospital stays while attenuating the
      surgical stress response. Multimodal analgesia is an important part of ERAS
      protocols. We compared and contrasted protocols from 15 institutions to test our
      hypothesis that there is a fundamental consensus among them. MATERIALS AND
      METHODS: ERAS protocols for open and laparoscopic colorectal surgery were
      compared from 15 different healthcare facilities. We examined each institution's
      approach to multimodal analgesia related to the use of oral and intravenous
      analgesics. Preoperative, intraoperative, and postoperative management was
      examined. RESULTS: All but three protocols used preoperative multimodal
      analgesics, with acetaminophen, celecoxib, and gabapentin being the most common.
      Intraoperative recommendations included the use of ketamine, lidocaine,
      magnesium, and ketorolac. Some protocols advocated for the use of opiates, while
      others aimed to minimize total opioid dose. In the postoperative period, the
      three most utilized agents were acetaminophen, nonsteroidal anti-inflammatory
      drugs (NSAIDs), and opioids. CONCLUSIONS: There were many similarities and some
      significant differences among ERAS protocols examined. Acetaminophen was the most
      widely used nonopioid agent and along with NSAIDs offers a benefit with respect
      to postoperative analgesia, opioid-sparing effects, earlier ambulation, and
      reduction in postoperative ileus. Gabapentin was widely used as it may reduce
      opioid consumption within the first 24 hours postoperatively. Lidocaine infusion
      was recommended if there were contraindications to or failure of epidural
      anesthesia. Ketamine is frequently recommended due to its analgesic,
      antihyperalgesic, antiallodynic, and antitolerance properties. Differences in
      approaches may be due to both institutional- and provider-level factors.

PMID- 28742428
TI  - Neck and Upper Limb Dysfunction in Patients following Neck Dissection: Looking
      beyond the Shoulder.
AB  - : Objective To measure patient-perceived upper limb and neck function following
      neck dissection and to investigate potential associations between clinical
      factors, symptoms, and function. Study Design Cross-sectional. Setting Two
      tertiary hospitals in Brisbane, Australia. Subjects and Methods Inclusion
      criteria: patients treated with neck dissection (2009-2014). EXCLUSION CRITERIA:
      aged <18 years, accessory nerve or sternocleidomastoid sacrifice, previous neck
      dissection, preexisting shoulder/neck injury, and inability to provide informed
      consent (cognition, insufficient English). Primary outcomes were self-reported
      function of the upper limb (Quick Disabilities of the Arm, Shoulder, and Hand)
      and neck (Neck Disability Index). Secondary outcomes included demographics,
      oncological management, self-efficacy, and pain. Generalized linear models were
      prepared to examine relationships between explanatory variables and self-reported
      function. Results Eighty-nine participants (male n = 63, 71%; median age, 62
      years; median 3 years since surgery) reported mild upper limb and neck
      dysfunction (median [quartile 1, quartile 3] scores of 11 [3, 32] and 12 [4, 28],
      respectively). Significant associations were found between worse upper limb
      function and longer time since surgery (coefficient, 1.76; 95% confidence
      interval [CI], 0.01-3.51), having disease within the thyroid (17.40; 2.37-32.44),
      postoperative radiation therapy (vs surgery only) (13.90; 6.67-21.14), and
      shoulder pain (0.65; 0.44-0.85). Worse neck function was associated with
      metastatic cervical lymph nodes (coefficient, 6.61; 95% CI, 1.14-12.08), shoulder
      pain (0.19; 0.04-0.34), neck pain (0.34; 0.21-0.47), and symptoms of neuropathic
      pain (0.61; 0.25-0.98). Conclusion Patients can experience upper limb and neck
      dysfunction following nerve-preserving neck dissection. The upper quadrant as a
      whole should be considered when assessing rehabilitation priorities after neck
      dissection.

PMID- 28742429
TI  - Relationship between housework and perceived happiness of middle-aged and older
      women in Taiwan-The moderating effect of health condition.
AB  - In this study, we investigated how physical health moderates the effect of
      housework on the perceived well-being in a sample of middle-aged and older women
      living with a partner in Taiwan. Two main findings were identified: First, the
      health status of middle-aged and older women moderates the relationship between
      their sense of housework fairness and perceived happiness. Second, the health
      status of their spouse moderates the relationship between their housework
      performance and perceived happiness.

PMID- 28742430
TI  - Sexual life of women in the climacterium: A community-based study.
AB  - Our purpose of conducting this community-based study was to determine sexual
      functions of women in climacterium and effects of menopausal symptoms on sexual
      functions. It was descriptive, cross-sectional, and community-based. The study
      sample consisted of 282 climacteric women. Menopause Rating Scale (MRS), Female
      Sexual Function Index (FSFI), and Sexual Satisfaction Scale for Women (SSS-W)
      were used for data collection. The total score was 13.42 +/- 8.82 for MRS, 18.73
      +/- 9.79 for FSFI, and 82.56 +/- 18.07 for SSS-W. Seventy-nine-point four percent
      of the women had sexual dysfunction. While complaints typical of the climacteric
      period increased, sexual functions and satisfaction decreased.

PMID- 28742431
TI  - Impact of Direct to Consumer Store-and-Forward Teledermatology on Access to Care,
      Satisfaction, Utilization, and Costs in a Commercial Health Plan Population.
AB  - PURPOSE: Store-and-forward teledermatology can improve access to dermatology by
      enabling asynchronous consults. This study assesses it on access, satisfaction,
      utilization, and costs in a commercial health plan setting. METHODOLOGY: In this
      prospective observational study with matched control, 47,411 individuals were
      provided access to teledermatology services staffed by board-certified, licensed
      dermatologists for 6 months. Two hundred forty-three individuals used the
      service. One hundred fifty-two participants successfully matched to similar users
      of in-person services for comparison. Average number of dermatology-related
      visits and dermatology-related costs in 30, 60, and 90 days postvisit, most
      frequent diagnoses, time to consult, patient satisfaction, and number of
      procedures were measured. RESULTS: Average time to consult for the
      teledermatology group was 16.31 h. Patient satisfaction was 4.38/5. Total
      dermatology utilization in the postvisit period for the teledermatology and the
      control groups respectively was 9 and 21 visits at 30 days (p = 0.074), 15 and 46
      visits at 60 days (p = 0.005), and 26 and 74 at 90 days (p = 0.001). The
      dermatology-related spend for the teledermatology and control groups,
      respectively, was $59 and $113 on the day of the initial consult (p < 0.01), $70
      and $202 for 30 days (p = 0.03), $78 and $ 221 for 60 days (p = 0.02), and $86
      and $307 for 90 days (p = 0.08) following initial visit. Total number of
      procedures conducted in the control group at the index visit was 26. In the
      postvisit period, the total number of procedures in the study and control groups,
      respectively, were 5 and 15 at 30 days (p = 0.053), 10 and 26 at 60 days (p =
      0.088), and 14 and 32 at 90 days (p = 0.082). CONCLUSIONS: Teledermatology
      services are accessible within hours and associated with high patient
      satisfaction. There is no evident increased utilization or costs postvisit.

PMID- 28742432
TI  - Controversies Surrounding Critical Care Nutrition: An Appraisal of Permissive
      Underfeeding, Protein, and Outcomes.
AB  - Over the past few years, numerous studies have called into question the optimal
      dose, timing, composition, and advancement rate of nutrition during the early
      acute phase of critical illness. These studies suggest permissive underfeeding
      with slow advancement may be more beneficial than aggressive full feeding. These
      counterintuitive results were possibly explained by enhanced autophagy, less
      hyperglycemia, or prevention of refeeding syndrome. This review underscores the
      controversies surrounding permissive underfeeding, aims to answer whether
      permissive underfeeding is appropriate for all critically ill patients, describes
      the impact of optimal protein delivery on critical care outcomes, discusses
      nutrition risk, and cogitates on the impact of nutrition on critical care
      outcomes.

PMID- 28742433
TI  - Breadth of the Socio-Ecological Model.

PMID- 28742434
TI  - Use of Regional Anesthesia Techniques: Analysis of Institutional Enhanced
      Recovery After Surgery Protocols for Colorectal Surgery.
AB  - INTRODUCTION: Principles of Enhanced Recovery After Surgery (ERAS(r)) protocols
      are well established, with the primary goal of optimizing perioperative care and
      recovery. The use of multimodal analgesia is a key component of these protocols,
      including regional analgesia techniques such as thoracic epidural analgesia
      (TEA), transversus abdominis plane (TAP), rectus sheath blocks or continuous
      wound infiltration (CWI)/catheters, and spinal anesthesia. We compare and
      contrast regional anesthesia approaches in different institutional colorectal
      surgery ERAS protocols. MATERIALS AND METHODS: ERAS protocols for open and
      laparoscopic colorectal surgery were obtained from 15 different healthcare
      facilities mostly located in North American and one in New Zealand. A comparison
      was then made with respect to regional anesthesia recommendations. RESULTS: The
      most commonly used regional technique among protocols was TEA. TAP blocks were
      the next most common, with rectus sheath blocks and continuous wound catheters
      only mentioned in one protocol each. CONCLUSION: There are both similarities and
      differences in regional anesthesia techniques, which may be due to institution-
      and provider-level factors. Most protocols advocate for TEA use, which has been
      associated with a lower incidence of paralytic ileus, attenuation of the surgical
      stress response, improved intestinal blood flow, improved analgesia, and
      reduction of opioid use. Use of spinal anesthesia may lead to earlier
      mobilization compared to TEA, and lower doses of intrathecal morphine are
      recommended to reduce respiratory depression. TAP blocks were indicated for
      laparoscopic procedures. Rectus sheath blocks, which are listed in some
      protocols, may provide analgesia equivalent to epidural anesthesia, while
      avoiding complications of TEA. CWI has been effective in reducing postoperative
      pain, hastening recovery, and improving pulmonary function.

PMID- 28742435
TI  - The Role of Transversus Abdominis Plane Blocks in Enhanced Recovery After Surgery
      Pathways for Open and Laparoscopic Colorectal Surgery.
AB  - INTRODUCTION: The concepts of Enhanced Recovery After Surgery (ERAS(r)) have
      steadily increased in usage, with benefits in patient outcomes and hospital
      length of stay. One important component of successful implementation of ERAS
      protocol is optimized pain control, via the multimodal approach, which includes
      neuraxial or regional anesthesia techniques and reduction of opioid use as the
      primary analgesic. Transversus abdominis plane (TAP) block is one such regional
      anesthesia technique, and it has been widely studied in abdominal surgery.
      MATERIALS AND METHODS: We performed an extensive literature search in MEDLINE and
      PubMed. We review the benefits of TAP blocks for colorectal surgery, both
      laparoscopic and open. We organize the data by surgery type, by method of TAP
      block performance, and by a comparison of TAP block to alternative analgesic
      techniques or to placebo. We examine different endpoints, such as postoperative
      pain, analgesic use, return of bowel function, and length of stay. RESULTS: The
      majority of studies examined TAP blocks in the context of laparoscopic colorectal
      surgery, with many, but not all, demonstrating significantly less use of
      postoperative opioids in comparison to placebo, wound infiltration, and standard
      postoperative patient-controlled analgesia with intravenous opioid
      administration. There is evidence that use of liposomal bupivacaine may be more
      effective than conventional long-acting local anesthetics. Noninferiority of TAP
      infusions has been demonstrated, compared with continuous thoracic epidural
      infusions. CONCLUSION: TAP blocks are easily performed, cost-effective, and an
      opioid-sparing adjunct for laparoscopic colorectal surgery, with minimal
      procedure-related morbidity. The evidence is in concordance with several of the
      goals of ERAS pathways.

PMID- 28742436
TI  - Factors associated with using research evidence in national sport organisations.
AB  - The purpose of this study was to explore factors associated with the use of
      research evidence in Canadian National Sport Organisations (NSOs). Data were
      collected via individual semi-structured interviews with 21 representatives from
      Canadian NSOs. A qualitative description approach was used. Interviews were
      transcribed verbatim and subjected to an inductive-to-deductive thematic
      analysis. A research implementation framework (Rycroft-Malone, 2004) was used to
      organise inductively derived themes into the higher-order categories of evidence
      (use of evidence, disconnection between research and practice), context (lack of
      capacity, organisational structure), and facilitation (personal connections with
      researchers and sport scientists, formal meetings with stakeholders). Overall,
      NSO representatives did not have a clear understanding of evidence and lacked
      capacity to access and translate research. However, some context factors, along
      with internal and external facilitators, were in place and could be used to
      enhance research implementation.

PMID- 28742437
TI  - Health and Safety Adoption from Use of a Risk Assessment Document on Irish Farms.
AB  - OBJECTIVES: This article describes levels of implementation of occupational
      health and safety (OHS) controls on a sample of Irish farms following completion
      of a risk assessment document (RAD) made available as part of a statutory code of
      practice (COP) for the agriculture sector. The article describes the legislation
      mandating the COP and the operation of a prevention initiative (PI) among key
      stakeholders to develop and promote farmer use of the COP and RAD. METHODS: RADs
      were collected for farmers (N = 475) and the number and type of OHS controls
      listed for action were tabulated. A farm audit of OHS standards and of
      implementation of controls listed for action in the RAD was undertaken among a
      randomly selected sample of farms (N = 94) where the RAD was completed. RESULTS:
      The study data indicates that farmers used the RAD to a limited extent, and that
      their focus in its use was on identifying physical rather than organizational
      controls. An association was found between farmers who actively implemented
      controls and positive OHS standards. Farm OHS standards were also associated with
      farmer attitude to OHS, farm enterprise, farmer age category, and work time
      needed to operate the farm. CONCLUSIONS: Overall, the study data suggests that
      standards of farm management are a crucial determinant of OHS standards. The
      study data also indicates that having knowledge of required OHS controls does not
      ensure implementation. Development of social learning in groups is considered as
      a significant means of increasing OHS farm adoption.

PMID- 28742438
TI  - Effect of Low-Level Laser Therapy on Bone Regeneration During Osseointegration
      and Bone Graft.
AB  - BACKGROUND: The effect of low-level laser therapy (LLLT) on bone regeneration
      during osseointegration and bone graft is very controversial. Despite many
      positive reports of in vitro and in vivo studies and more than 50 randomized
      clinical trials claiming a positive effect of photobiomodulation (PBM), many
      reports found no significant effect of lasers. OBJECTIVE: The aim of this study
      was to evaluate studies correlating PBM and bone regeneration and to assesses
      parameters that produce positive results based on dose and output power used.
      MATERIALS AND METHODS: Four electronic databases were used: PubMed, Springer,
      Google Scholar, and Cochrane. RESULTS: The research yielded 230 articles. The
      full texts of all articles were evaluated and scored using eligibility criteria
      adapted from Cericato et al. After evaluation, only 19 articles met the inclusion
      criteria. CONCLUSIONS: A positive effect of low-level laser energy on bone
      regeneration within a certain relationship between dose and output power was
      found. LLLT stimulates cellular metabolism, increasing protein synthesis and
      subsequent bone regeneration. A high dose combined with low power or a low dose
      combined with high power appears to produce a positive effect.

PMID- 28742439
TI  - DaMab-2: Anti-Human DGKalpha Monoclonal Antibody for Immunocytochemistry.
AB  - Diacylglycerol kinase (DGK) is responsible for the enzymatic conversion of
      diacylglycerol to phosphatidic acid. Since both diacylglycerol and phosphatidic
      acid serve as signaling molecules, DGK is regarded as a hub between
      diacylglycerol-mediated and phosphatidic acid-mediated signaling. One of the 10
      DGK isozymes, DGKalpha, is shown to be involved in T cell function. Transfection
      studies using tagged expression vectors revealed that DGKalpha localizes to the
      cytoplasm and nucleus and translocates to the plasma membrane in response to T
      cell receptor stimulation. However, a limited number of studies reported the
      localization of native protein of DGKalpha in tissues and cells. In this study,
      we immunized mice with recombinant DGKalpha and developed several anti-DGKalpha
      monoclonal antibodies (mAbs). One of the established anti-DGKalpha mAbs is a
      clone DaMab-2 (mouse IgG1, kappa). In enzyme-linked immunosorbent assay, DaMab-2
      recognized only DGKalpha, and did not react with the other isozymes, such as
      DGKgamma, DGKzeta, DGKeta, and DGKdelta. Importantly, DaMab-2 is very useful in
      immunocytochemical analysis of human cultured cells, indicating that DaMab-2 is
      advantageous to analyze the localization and function of DGKalpha.

PMID- 28742440
TI  - Retraction of: "Long-Term Outcomes of Hepatectomy for Bilateral Hepatolithiasis
      with Three-Dimensional Reconstruction: A Propensity Score Matching Analysis" J
      Laparoendosc Adv Surg Tech A. 2016;26:9;680-688. DOI: 10.1089/lap.2016.0165.

PMID- 28742441
TI  - Principles of care for women experiencing intimate partner violence: Views of
      expert Japanese health professionals and advocates.
AB  - In Japan, interventions for Intimate Partner Violence (IPV) in the health care
      setting are rare, partly due to Japanese cultural norms that marginalize women's
      IPV experiences. A thematic analysis of narratives of eight Japanese health
      professionals who are experts in IPV care identified shared core values and
      practices that have guided their development of culturally relevant IPV
      interventions: supporting women's autonomy to define what is at stake for her,
      appreciating unique trajectories and timing for recovery, and practicing shared
      decision-making. These shared practices may be essential for training health
      professionals to respond to IPV in Japan and elsewhere.

PMID- 28742442
TI  - Analysis of Variability in Intraoperative Fluid Administration for Colorectal
      Surgery: An Argument for Goal-Directed Fluid Therapy.
AB  - BACKGROUND: Fluid therapy in the perioperative period varies greatly between
      anesthesia providers and may have a negative impact on surgical outcomes.
      METHODS: We conducted a retrospective analysis of 705 elective colorectal cases
      consisting of colectomies, ileocolic resections, and low anterior resections at
      an academic institution from January 1, 2010 to May 29, 2015, collected by our
      electronic medical record before implementation of Enhanced Recovery After
      Surgery (ERAS(r)) pathways. RESULTS: The mean for total crystalloid
      administration was 2578 mL with a standard deviation (SD) that was approximately
      50% of the mean value. A combination of both normal saline and lactated Ringer's
      solution was used in almost all cases without a clear rationale for fluid choice.
      Fluid administered to patients was disproportional to measured intraoperative
      fluid losses (estimated blood loss and urine output) by a factor of 10. The
      average rate of fluid given was 1050 mL/h with an SD of nearly the same amount
      (951 mL). There was a variability of over 67% in total crystalloid administered
      based on both ideal body weight and total body weight. CONCLUSIONS: We found that
      a wide variability in the amount and type of fluid therapy administered existed
      at our institution before implementation of a colorectal ERAS pathway or routine
      use of goal-directed fluid therapy (GDFT). ERAS pathways with GDFT protocols
      could lead to more rational and consistent fluid therapy leading to improved
      outcomes.

PMID- 28742443
TI  - Family planning in Southern India: A survey of women's attitudes.
AB  - Women were recruited from villages in the Belgaum district of India. Members of
      the research team obtained consent and led 58 interviews in the local languages.
      Participants were asked questions covering topics related to postpartum
      contraceptive counseling, knowledge, and experience; postpartum sexual practice;
      birth spacing desire and counseling; and interest in long-acting reversible
      contraceptives (LARCs). Women generally desired 3 years of birth spacing. A
      majority did not receive counseling regarding postpartum contraception during the
      prenatal period, although most would have liked to have received such counseling.
      Those who had made a contraceptive plan during the prenatal period had an odds
      ratio of 25.2 (95% CI 4.9-128.6, p = 0.00001) for using postpartum contraception.
      Influences on contraceptive decisions primarily came from friends and family,
      while information from medical providers was not a major influence. Most women
      did not believe they could make their own decisions regarding contraception use,
      but those who did had an adjusted odds ratio of 56 (95% CI 3.4-9161, p = 0.0047)
      of utilizing postpartum contraception. Women generally liked the idea of LARCs. A
      large majority of the women surveyed (89.66%) liked the idea of a subdermal
      contraceptive implant, a method currently unavailable in this region. Ultimately,
      the women surveyed do have healthy attitudes and goals regarding birth spacing
      but few utilize effective contraception in order to meet their goals. Further
      efforts in counseling as well as availability of a wider variety of contraceptive
      methods, including the subdermal contraceptive implant, may decrease the
      disparity between desires and practices.

PMID- 28742445
TI  - Becoming lesbian: Monique Wittig's queer-trans-feminism.
AB  - Inspired by Lynne Huffer's queer feminist genealogy, this article explores queer
      trans-feminism as a project that would bring together queer, feminist, and
      transgender theory and politics into a shared critical lineage. I suggest that
      Monique Wittig is a neglected thinker who could re-enliven connections and
      debates within queer, feminist, and trans theory and politics. Utilizing recent
      historiographies of queer and feminist theory, I imagine what it would mean to
      hold on to the figure of the lesbian as a figure for queer-trans-feminist
      politics rather than render the lesbian anachronistic. I then explore the
      implications of Wittig's notion that "lesbians are not women" for a queer-trans
      feminism. I argue that Wittig's critique of the language of the social sciences
      offers queer-trans-feminist scholars a source for contemporary self-critique and
      coalition.

PMID- 28742447
TI  - A crisis emerges: Lesbian health between breast cancer and HIV/AIDS.
AB  - In this essay, I argue that lesbians have come to be a population of concern for
      state-based health organizations as a result of lesbian health activism that drew
      connections between breast cancer and HIV/AIDS. In order to develop this
      analysis, I tell the story of the rise of lesbian breast cancer activism in
      concert with HIV/AIDS in San Francisco in the early 1990s. The state recognition
      of lesbian health needs, and with it the solidification of lesbian as a
      biopolitical category, was catalyzed by associations with the AIDS crisis and HIV
      activism, but also required an articulated difference, or lesbian specificity,
      which breast cancer provided. And yet, documenting the multiple, and potentially
      contradictory, ways that these associations were made resists understanding
      "lesbian" as a static category.

PMID- 28742446
TI  - Sleep and Pain in Mid- to Late-Life: An Exploration of Day-to-Day Pain
      Inconsistency.
AB  - OBJECTIVES: This study examined how different quantifications of pain (average
      vs. day-to-day inconsistency) are related to sleep in older adults beyond known
      predictors. METHODS: Baseline measures from the Active Adult Mentoring Project
      were used for secondary analyses. Participants included 82 adults in mid- to late
      life. Depression was assessed with the BDI-II. Pain intensity was assessed over
      seven days on a 11-point Likert-scale, while sleep efficiency (SE), total sleep
      time (TST), and total wake time (TWT) were assessed using a self-report diary.
      RESULTS: Regression analyses revealed that pain inconsistency was associated with
      both SE and TWT and accounted for significant variance over age, gender, and
      depression. In contrast, average pain was not associated with SE, TST, or TWT.
      CONCLUSIONS: The findings indicate that pain inconsistency may be a more
      meaningful predictor of sleep disturbance than average pain level, suggesting
      that one's ability to regulate pain may be related to one's ability to engage in
      optimal sleep in mid- to late-life. CLINICAL IMPLICATIONS: Pain inconsistency
      appears to contribute more to sleep disturbance than average pain. Pain
      inconsistency in late-life warrants greater attention and may be an area of
      clinical intervention through activity-pacing or coping skills training.

PMID- 28742448
TI  - Psychometric Properties of the Thai Internalized Stigma Scale (TIS-LCH) for Care
      Home Residents.
AB  - OBJECTIVES: Living in a care home is a source of stigma in Thai culture, although
      there is currently no measurement tool in the Thai language specifically designed
      to assess internalized stigma in care home residents. The Thai Version of
      Internalized Stigma of Living in a Care Home (TIS-LCH) scale was developed and
      tested for its psychometric properties among Thai older residents. METHODS: The
      Thai version of Internalized Stigma of Mental Health Illness (ISMI) Scale was
      revised into the TIS-LCH by replacing the word of "mental health illness" to
      "living in a care home." Content validity of the TIS-LCH was determined through
      expert review (n = 6), and reliability testing was undertaken with older care
      home residents (n = 128). RESULTS: The TIS-LCH showed good internal consistency,
      with a Cronbach's alpha of .87. Test-retest reliability coefficient of TIS-LCH
      was excellent for the full scale (ICC = .90). CONCLUSIONS: The Thai version of IS
      LCH (TIS-LCH) is a valid and reliable measurement tool for assessing internalized
      stigma in Thai care home residents. CLINICAL IMPLICATIONS: The IS-LCH will be a
      useful research tool to assess internalized stigma in older adults living in care
      settings. Understanding stigma will help health and social care professionals to
      plan interventions aimed at reducing or preventing negative emotional reactions
      and negative behavioural responses toward stigma, which are known to be
      associated with mental illness and particularly depression among this population.

PMID- 28742449
TI  - A Case History Introducing the Oregon Ag Seminar Series-Keys to Program and
      Research-to-Practice Success.
AB  - This case history of Oregon state's Ag Seminar Series is consistent with the
      Socio-Ecological Model, demonstrating how policy at a state level can influence
      an organizational approach with impacts that ultimately influence safety
      practices on the farm. From modest beginnings, the Ag Seminar Series, offered
      through a workers compensation insurance company, now serves over 2,300 Oregon
      farmers annually in English and Spanish. This case offers unique but also
      replicable methods for educators, insurers, and researchers in safety education,
      safety motivators, and research-to-practice (r2p).

PMID- 28742450
TI  - "Keep Me Doing What I Love": A Photovoice Evaluation of the Missouri AgrAbility
      Project.
AB  - The Missouri AgrAbility program links the Cooperative Extension Service at a land
      grant university with a nonprofit disability organization to provide practical
      education and assistance that promotes rural independence. This project utilized
      Photovoice to describe how Missouri AgrAbility clients perceived how the program
      impacts their lives. This article relates clients' perceptions of the impact of
      the AgrAbility program on their lives to the socio-ecologic model framework.
      Although the primary focus of AgrAbility is to help individuals who have
      disabilities maintain their independence, all levels of the socio-ecological
      model are integral in meeting the needs of program participants.

PMID- 28742451
TI  - Think of It Again, Apply It Anew: The Socio-Ecological Model and Farm Safety.

PMID- 28742452
TI  - "The third sex is here to stay": Rhetorical reconstructions of lesbian sexuality
      in Vice Versa.
AB  - Vice Versa, published in Los Angeles from 1947-1948 and regarded as the first
      lesbian periodical in the United States, was authored and edited by Lisa Ben
      (anagram for "lesbian"). While Vice Versa is lauded for inspiring later lesbian
      publications, little scholarship has analyzed the magazine's contents. Queer
      rhetorical analysis allows me to demonstrate the integral role Vice Versa played
      in counteracting cultural and medical classifications of lesbians during the
      1940s. Through an analysis of Vice Versa's book and movie reviews, an editorial,
      and creative writing, this article analyzes the way Ben uses queer rhetoric to
      turn narratives of medical and psychological deviancy and inferiority into a
      means for empowerment and community building. By foregrounding queer rhetorical
      and discursive means through which the periodical engaged with and pushed back on
      culturally dominant views of lesbians as psychologically or biologically
      "inverted" and deviant within newspapers, film, and novels, my analysis of Vice
      Versa calls attention to the processes through which the magazine negotiated
      lesbian identity creation with dominant tropes that categorized lesbian bodies
      and desires as debased.

PMID- 28742453
TI  - Complete Serologic Response to Pembrolizumab in a Woman With Chemoresistant
      Metastatic Choriocarcinoma.

PMID- 28742454
TI  - Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly
      Diagnosed Multiple Myeloma: A Meta-Analysis.
AB  - Purpose Lenalidomide maintenance therapy after autologous stem-cell
      transplantation (ASCT) demonstrated prolonged progression-free survival (PFS)
      versus placebo or observation in several randomized controlled trials (RCTs) of
      patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the
      primary end point, and none were powered for overall survival (OS) as a primary
      end point. Thus, a meta-analysis was conducted to better understand the impact of
      lenalidomide maintenance in this setting. Patients and Methods The meta-analysis
      was conducted using primary-source patient-level data and documentation from
      three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie
      Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myelome
      2005-02) that met the following prespecified inclusion criteria: an RCT in
      patients with NDMM receiving ASCT followed by lenalidomide maintenance versus
      placebo or observation with patient-level data available and achieved database
      lock for primary efficacy analysis. Results Overall, 1,208 patients were included
      in the meta-analysis (605 patients in the lenalidomide maintenance group and 603
      in the placebo or observation group). The median PFS was 52.8 months for the
      lenalidomide group and 23.5 months for the placebo or observation group (hazard
      ratio, 0.48; 95% CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for
      all surviving patients, the median OS had not been reached for the lenalidomide
      maintenance group, whereas it was 86.0 months for the placebo or observation
      group (hazard ratio, 0.75; 95% CI, 0.63 to 0.90; P = .001). The cumulative
      incidence rate of a second primary malignancy before disease progression was
      higher with lenalidomide maintenance versus placebo or observation, whereas the
      cumulative incidence rates of progression, death, or death as a result of myeloma
      were all higher with placebo or observation versus lenalidomide maintenance.
      Conclusion This meta-analysis demonstrates a significant OS benefit and confirms
      the PFS benefit with lenalidomide maintenance after ASCT in patients with NDMM
      when compared with placebo or observation.

PMID- 28742455
TI  - Chemoimmunotherapy Is Not Dead Yet in Chronic Lymphocytic Leukemia.

PMID- 28742457
TI  - Epidemic Network Analysis for Mitigation of Invasive Pathogens in Seed Systems:
      Potato in Ecuador.
AB  - Seed systems have an important role in the distribution of high-quality seed and
      improved varieties. The structure of seed networks also helps to determine the
      epidemiological risk for seedborne disease. We present a new approach for
      evaluating the epidemiological role of nodes in seed networks, and apply it to a
      regional potato farmer consortium (Consorcio de Productores de Papa [CONPAPA]) in
      Ecuador. We surveyed farmers to estimate the structure of networks of farmer seed
      tuber and ware potato transactions, and farmer information sources about pest and
      disease management. Then, we simulated pathogen spread through seed transaction
      networks to identify priority nodes for disease detection. The likelihood of
      pathogen establishment was weighted based on the quality or quantity of
      information sources about disease management. CONPAPA staff and facilities, a
      market, and certain farms are priorities for disease management interventions
      such as training, monitoring, and variety dissemination. Advice from agrochemical
      store staff was common but assessed as significantly less reliable. Farmer access
      to information (reported number and quality of sources) was similar for both
      genders. However, women had a smaller amount of the market share for seed tubers
      and ware potato. Understanding seed system networks provides input for scenario
      analyses to evaluate potential system improvements. [Formula: see text] Copyright
      (c) 2017 The Author(s). This is an open access article distributed under the CC
      BY 4.0 International license .

PMID- 28742456
TI  - Dietary Fat Intake and Lung Cancer Risk: A Pooled Analysis.
AB  - Purpose Dietary fat may play a role in lung carcinogenesis. Findings from
      epidemiologic studies, however, remain inconsistent. In this pooled analysis of
      10 prospective cohort studies from the United States, Europe, and Asia, we
      evaluated the associations of total and specific types of dietary fat with lung
      cancer risk. Methods Cox regression was used to estimate hazard ratios (HRs) and
      95% CIs in each cohort. Study-specific risk estimates were pooled by random- or
      fixed-effects meta-analysis. The first 2 years of follow-up were excluded to
      address potential influence of preclinical dietary changes. Results Among
      1,445,850 participants, 18,822 incident cases were identified (mean follow-up,
      9.4 years). High intakes of total and saturated fat were associated with an
      increased risk of lung cancer (for highest v lowest quintile: HR, 1.07 and 1.14,
      respectively; 95% CI, 1.00 to 1.15 and 1.07 to 1.22, respectively; P for trend
      for both < .001). The positive association of saturated fat was more evident
      among current smokers (HR, 1.23; 95% CI, 1.13 to 1.35; P for trend < .001) than
      former/never smokers ( P for interaction = .004), and for squamous cell and small
      cell carcinoma (HR, 1.61 and 1.40, respectively; 95% CI, 1.38 to 1.88 and 1.17 to
      1.67, respectively; P for trend for both < .001) than other histologic types ( P
      for heterogeneity < .001). In contrast, a high intake of polyunsaturated fat was
      associated with a decreased risk of lung cancer (HR, 0.92; 95% CI, 0.87 to 0.98
      for highest v lowest quintile; P for trend = .02). A 5% energy substitution of
      saturated fat with polyunsaturated fat was associated with a 16% to 17% lower
      risk of small cell and squamous cell carcinoma. No associations were found for
      monounsaturated fat. Conclusion Findings from this large, international cohort
      consortium suggest that modifying dietary fat intake (ie, replacing saturated fat
      with polyunsaturated fat) may reduce lung cancer risk, particularly among smokers
      and for squamous cell and small cell carcinoma.

PMID- 28742458
TI  - Morphological and Genetic Analyses of the Invasive Forest Pathogen Phytophthora
      austrocedri Reveal that Two Clonal Lineages Colonized Britain and Argentina from
      a Common Ancestral Population.
AB  - Phytophthora austrocedri is causing widespread mortality of Austrocedrus
      chilensis in Argentina and Juniperus communis in Britain. The pathogen has also
      been isolated from J. horizontalis in Germany. Isolates from Britain, Argentina,
      and Germany are homothallic, with no clear differences in the dimensions of
      sporangia, oogonia, or oospores. Argentinian and German isolates grew faster than
      British isolates across a range of media and had a higher temperature tolerance,
      although most isolates, regardless of origin, grew best at 15 degrees C and all
      isolates were killed at 25 degrees C. Argentinian and British isolates caused
      lesions when inoculated onto both A. chilensis and J. communis; however, the
      Argentinian isolate caused longer lesions on A. chilensis than on J. communis and
      vice versa for the British isolate. Genetic analyses of nuclear and mitochondrial
      loci showed that all British isolates are identical. Argentinian isolates and the
      German isolate are also identical but differ from the British isolates. Single
      nucleotide polymorphisms are shared between the British and Argentinian isolates.
      We concluded that British isolates and Argentinian isolates conform to two
      distinct clonal lineages of P. austrocedri founded from the same as-yet
      unidentified source population. These lineages should be recognized and treated
      as separate risks by international plant health legislation.

PMID- 28742459
TI  - Identification of Clusters that Condition Resistance to Anthracnose in the Common
      Bean Differential Cultivars AB136 and MDRK.
AB  - The correct identification of the anthracnose resistance systems present in the
      common bean cultivars AB136 and MDRK is important because both are included in
      the set of 12 differential cultivars proposed for use in classifying the races of
      the anthracnose causal agent, Colletrotrichum lindemuthianum. In this work, the
      responses against seven C. lindemuthianum races were analyzed in a recombinant
      inbred line population derived from the cross AB136 * MDRK. A genetic linkage map
      of 100 molecular markers distributed across the 11 bean chromosomes was developed
      in this population to locate the gene or genes conferring resistance against each
      race, based on linkage analyses and chi2 tests of independence. The identified
      anthracnose resistance genes were organized in clusters. Two clusters were found
      in AB136: one located on linkage group Pv07, which corresponds to the anthracnose
      resistance cluster Co-5, and the other located at the end of linkage group Pv11,
      which corresponds to the Co-2 cluster. The presence of resistance genes at the Co
      5 cluster in AB136 was validated through an allelism test conducted in the F2
      population TU * AB136. The presence of resistance genes at the Co-2 cluster in
      AB136 was validated through genetic dissection using the F2:3 population ABM3 *
      MDRK, in which it was directly mapped to a genomic position between 46.01 and
      47.77 Mb of chromosome Pv11. In MDRK, two independent clusters were identified:
      one located on linkage group Pv01, corresponding to the Co-1 cluster, and the
      second located on LG Pv04, corresponding to the Co-3 cluster. This report
      enhances the understanding of the race-specific Phaseolus vulgaris-C.
      lindemuthianum interactions and will be useful in breeding programs.

PMID- 28742460
TI  - Resistance Genes in Global Crop Breeding Networks.
AB  - Resistance genes are a major tool for managing crop diseases. The networks of
      crop breeders who exchange resistance genes and deploy them in varieties help to
      determine the global landscape of resistance and epidemics, an important system
      for maintaining food security. These networks function as a complex adaptive
      system, with associated strengths and vulnerabilities, and implications for
      policies to support resistance gene deployment strategies. Extensions of epidemic
      network analysis can be used to evaluate the multilayer agricultural networks
      that support and influence crop breeding networks. Here, we evaluate the general
      structure of crop breeding networks for cassava, potato, rice, and wheat. All
      four are clustered due to phytosanitary and intellectual property regulations,
      and linked through CGIAR hubs. Cassava networks primarily include public breeding
      groups, whereas others are more mixed. These systems must adapt to global change
      in climate and land use, the emergence of new diseases, and disruptive breeding
      technologies. Research priorities to support policy include how best to maintain
      both diversity and redundancy in the roles played by individual crop breeding
      groups (public versus private and global versus local), and how best to manage
      connectivity to optimize resistance gene deployment while avoiding risks to the
      useful life of resistance genes. [Formula: see text] Copyright (c) 2017 The
      Author(s). This is an open access article distributed under the CC BY 4.0
      International license .

PMID- 28742461
TI  - Environmental sciences, reality television, and western values.

PMID- 28742462
TI  - A novel iris transillumination grading scale allowing flexible assessment with
      quantitative image analysis and visual matching.
AB  - PURPOSE: To develop a sensitive scale of iris transillumination suitable for
      clinical and research use, with the capability of either quantitative analysis or
      visual matching of images. METHODS: Iris transillumination photographic images
      were used from 70 study subjects with ocular or oculocutaneous albinism. Subjects
      represented a broad range of ocular pigmentation. A subset of images was
      subjected to image analysis and ranking by both expert and nonexpert reviewers.
      Quantitative ordering of images was compared with ordering by visual inspection.
      Images were binned to establish an 8-point scale. Ranking consistency was
      evaluated using the Kendall rank correlation coefficient (Kendall's tau). Visual
      ranking results were assessed using Kendall's coefficient of concordance
      (Kendall's W) analysis. RESULTS: There was a high degree of correlation among the
      image analysis, expert-based and non-expert-based image rankings. Pairwise
      comparisons of the quantitative ranking with each reviewer generated an average
      Kendall's tau of 0.83 +/- 0.04 (SD). Inter-rater correlation was also high with
      Kendall's W of 0.96, 0.95, and 0.95 for nonexpert, expert, and all reviewers,
      respectively. CONCLUSIONS: The current standard for assessing iris
      transillumination is expert assessment of clinical exam findings. We adapted an
      image-analysis technique to generate quantitative transillumination values.
      Quantitative ranking was shown to be highly similar to a ranking produced by both
      expert and nonexpert reviewers. This finding suggests that the image
      characteristics used to quantify iris transillumination do not require expert
      interpretation. Inter-rater rankings were also highly similar, suggesting that
      varied methods of transillumination ranking are robust in terms of producing
      reproducible results.

PMID- 28742465
TI  - Engaging Agribusinesses: Feasibility and Cost of an ATV Safety Poster Project.
AB  - OBJECTIVES: All-terrain vehicle (ATV)-related deaths and injuries continue to be
      a significant problem. Influential change agents such as agribusinesses could be
      important partners for improving safety behaviors among rural ATV users. Our
      objective was to determine how effectively an injury prevention project could
      engage agribusinesses through the postal service and to assess their willingness
      to display a safety poster. METHODS: One thousand two hundred forty-four
      agribusinesses received an ATV safety poster and a postcard survey by mail. A
      randomized sampling of these businesses was surveyed by telephone 4-7 weeks
      later. Telephone survey questions included whether they recalled receiving the
      poster, and if so, whether, where and how long the poster was displayed. RESULTS:
      One hundred six postcards were returned. Of the 192 eligible business persons
      contacted by telephone, 89% agreed to participate. Approximately one-third of
      telephone survey participants recalled receiving the poster. Among these, 81%
      with walk-in customers posted it, and 74% still had it displayed 1 month later.
      Of participants who did not recall receiving the poster, 83% stated they would
      have displayed the poster. The cost of displaying each poster in a business was
      16.6 cents/day during the first month. Final costs/day would be much less because
      of continued display. CONCLUSION: A high percentage of agribusinesses displayed
      or would have displayed an ATV safety poster, and most displayed it beyond 1
      month. Unfortunately, participant recruitment via postal delivery alone was
      challenging. Nevertheless, mass mailing of injury prevention materials to be
      displayed in the retail setting may be a low cost method for raising safety
      awareness.

PMID- 28742466
TI  - Aphasia and Dysarthria in Acute Stroke: Recovery and Functional Outcome.
AB  - Background Aphasia and dysarthria have major implications for activities of daily
      living and social participation following stroke. Few studies describe recovery
      in the acute stroke setting. We described the evolution of aphasia and dysarthria
      by three-months poststroke. Methods We conducted a retrospective analysis of
      pooled clinical trial data from the Virtual International Stroke Trials Archive.
      We defined aphasia and dysarthria at baseline as a score of >=1 on the Best
      Language (Item 9) and Dysarthria (Item 10) domains of the National Institutes of
      Health Stroke Scale, respectively. We described recovery from these impairments
      by three-months. Covariate adjusted analyses described the associations between
      aphasia, dysarthria, and functional outcome using the modified Rankin Scale at
      three-months following stroke. Results At baseline, 4039/8904 (45.4%) people
      presented with aphasia and 6192 (69.5%) with dysarthria; 2639 (29.6%) had both
      impairments. By three-months, aphasia and dysarthria had resolved in 1292/7219
      (17.9%) and 2892/7219 (40.1%) survivors, respectively, but persisted in 1713/7219
      (23.7%) and 1940/7219 (27%), respectively. Age and severity of initial stroke
      were associated with poor recovery, whereas thrombolysis was associated with
      improved recovery. Aphasia at baseline [ P = 0.049, odds ratio = 0.89, 95%
      confidence interval (0.79,1.00)] and persistent aphasia at three-months [ P <
      0.0001, odds ratio = 0.31, 95% confidence interval (0.27, 0.35)] were each
      associated with poorer modified Rankin Scale scores at three-months. Conclusion
      Aphasia or dysarthria persisted in at least a quarter of people in our dataset at
      three-months following stroke. The association between persistent aphasia at
      three-months and poor modified Rankin Scale renders this impairment a major
      therapeutic target for recovery and restitution.

PMID- 28742467
TI  - Polycystic Ovary Syndrome in Adolescents: Which MR Imaging-based Diagnostic
      Criteria?
AB  - Purpose To evaluate the validity and reproducibility of magnetic resonance (MR)
      imaging-based ovarian morphologic measurements for diagnosis of polycystic ovary
      syndrome (PCOS) in adolescents. Materials and Methods This case-control study
      included 110 adolescent girls (age range, 13-17 years) who underwent pelvic MR
      imaging in 2006-2015. The case group included girls with high (n = 40,
      hyperandrogenism and oligomenorrhea or amenorrhea), intermediate (n = 8,
      hyperandrogenism), or low (n = 7, oligomenorrhea or amenorrhea) suspicion of
      PCOS. Control subjects were 55 age-matched (+/- 2 years) girls with no clinical
      hyperandrogenism, oligomenorrhea, or amenorrhea. The validity (sensitivity,
      specificity, and area under the receiver operating characteristic curve [AUC]) of
      the number of follicles per ovary (FPO) measuring 9 mm or smaller (FPO-9) and FPO
      measuring 5 mm or smaller (FPO-5), ovarian volume (OV), sphericity index,
      peripheral distribution of follicles, and absence of a dominant follicle were
      determined, with girls who were highly suspected of having PCOS compared with
      control subjects as the reference. Two radiologists independently measured these
      criteria in 50 girls who were suspected of having PCOS to assess reproducibility
      (kappa and intraclass correlation coefficients [ICCs]). Results All criteria
      except sphericity index and absence of a dominant follicle were significantly
      associated with the level of suspicion of PCOS (P <= .05). The AUCs for FPO-9
      (0.78; 95% confidence interval [CI]: 0.68, 0.87), FPO-5 (0.73; 95% CI: 0.62,
      0.83), and OV (0.77; 95% CI: 0.68, 0.87) were significantly greater than 0.5;
      that was not true for sphericity index (AUC, 0.58; 95% CI: 0.47, 0.70).
      Sensitivity and specificity for peripheral distribution of follicles were 33%
      (95% CI: 19%, 49%) and 95% (95% CI: 85%, 99%), respectively; for absence of a
      dominant follicle, they were 90% (95% CI: 76%, 97%) and 27% (95% CI: 16%, 41%),
      respectively. Reproducibility was almost perfect for OV (ICC, 0.89), substantial
      for absence of a dominant follicle (kappa, 0.74), moderate for FPO-9 (ICC, 0.54)
      and FPO-5 (ICC, 0.61), and fair for peripheral distribution of follicles (kappa,
      0.37). Conclusion The most accurate MR imaging-based diagnostic criteria for PCOS
      were OV, FPO-9, and peripheral distribution of follicles; however,
      reproducibility of these measures was moderate, except that for OV (ICC, 0.89).
      (c) RSNA, 2017 Online supplemental material is available for this article.

PMID- 28742468
TI  - Single CT Scan Prolongs Survival by Extending Cancer Latency in Trp53
      Heterozygous Mice.
AB  - There is growing concern over the effects of medical diagnostic procedures on
      cancer risk. Although numerous studies have demonstrated that low doses of
      ionizing radiation can have protective effects including reduced cancer risk and
      increasing lifespan, the hypothesis that any radiation exposure increases cancer
      risk still predominates. In this study, we investigated cancer development and
      longevity of cancer-prone Trp53+/- mice exposed at 7-8 weeks of age to a single
      10 mGy dose from either a diagnostic CT scan or gamma radiation. Mice were
      monitored daily for adverse health conditions until they reached end point.
      Although the median lifespan of irradiated mice was extended compared to control
      animals, only CT scanned mice lived significantly longer than control mice (P <
      0.004). There were no differences in the frequency of malignant cancers between
      the irradiated and control groups. Exposure to a single CT scan caused a
      significant increase in the latency of sarcoma and carcinoma (P < 0.05),
      accounting for the increased lifespan. This study demonstrates that low-dose
      exposure, specifically a single 10 mGy CT scan, can prolong lifespan by
      increasing cancer latency in cancer-prone Trp53+/- mice. The data from this
      investigation add to the large body of evidence, which shows that risk does not
      increase linearly with radiation dose in the low-dose range.

PMID- 28742469
TI  - When Fairness Clashes with Personal Autonomy and Parental Authority: A Comparison
      of Daughters' and Mothers' Reasoning in Two Cultural Contexts in Turkey.
AB  - The author examined religious and secular daughters' and mothers' reasoning about
      personal autonomy, maternal authority, and moral concepts in family decision
      making situations in urban Turkey. Sixty-eight daughters and 34 mothers were
      individually interviewed about decision-making autonomy in general issues and
      hypothetical daughter-mother conflicts. Results indicated participants regardless
      of their family status and religious background assigned more decision-making
      autonomy to mothers when evaluating general issues. Analysis of controversial
      issues as hypothetical conflicts indicated that daughters and mothers do not hold
      unitary social judgments about the social world that were always consistent with
      the norms of their community and family status. There were some religious
      background differences in evaluations of some conflict stories as a function of
      whether they evaluated the choices as moral, conventional, personal, and
      prudential matters. Although secular and religious participants conceptualized
      daughters and mothers in relational terms rather than characterizing the
      relations and social issues by harmony, obedience to authority, and acceptance of
      norms findings suggested that secular women evaluated the hypothetical adolescent
      mother conflicts more consistently when the issue entails violation of a moral
      principle such as justice, fairness, and well-being of the other.

PMID- 28742470
TI  - Femtosecond studies: observing transition states and other ultra-short-lived
      species.
AB  - To celebrate 2015 as the 'International Year of Light', this article offers a
      short survey of the progress made since the award of the Nobel Prize of 1999 to
      Professor Ahmed Zewail for his pioneering work on taking the timescale for
      observation of light-induced events down to the femtosecond level. Developments
      have included the extension of studies (i) to larger molecules, leading up to
      biological systems; (ii) the increased range of detection methods of transient
      species from the UV-Vis to the infrared region; (iii) the introduction of Raman
      spectroscopy to augment IR studies; (iv) examination of combination events to
      supplement dissociation events; (v) the interrogation of transient structures by
      X-ray absorption spectroscopy; (vi) the study of reactions taking place at solid
      surfaces.

PMID- 28742471
TI  - Beyond the Discovery Void: New targets for antibacterial compounds.
AB  - Antibiotics save many lives, but their efficacy is under threat:
      overprescription, population growth, and global travel all contribute to the
      rapid origination and spread of resistant strains. Exacerbating this threat is
      the fact that no new major classes of antibiotics have been discovered in the
      last 30 years: this is the "discovery void." We discuss the traditional molecular
      targets of antibiotics as well as putative novel targets.

PMID- 28742472
TI  - Bacteriophage endolysins and their applications.
AB  - Endolysins (lysins) are bacteriophage-encoded enzymes that have evolved to
      degrade specific bonds within the bacterial cell wall. These enzymes represent a
      novel class of antibacterial agents against infectious pathogens, especially in
      light of multidrug-resistant bacteria, which have made antibiotic therapy
      increasingly redundant. Lysins have been used successfully to eliminate/control
      bacterial pathogens in various anatomical locations in mouse and other animal
      models. Engineering tactics have also been successfully applied to improve lysin
      function. This review discusses the structure and function of lysins. It
      highlights protein-engineering tactics utilised to improve lysin activity. It
      also reviews the applications of lysins towards food biopreservation,
      therapeutics, biofilm elimination and diagnostics.

PMID- 28742473
TI  - Modelling Ebola.
AB  - This paper is the combination of a review on the problems of data collection and
      modelling efforts of the recent Ebola epidemics. After a brief review of data
      availability, the modelling frameworks have been discussed. Both deterministic
      and stochastic models have been reviewed and supplemented with a short discussion
      of some problems of parameter estimation. The methods have been illustrated by a
      realistic case study. A hint is given for the scope and limits of prediction and
      control.

PMID- 28742474
TI  - X makes nine: a distant ice giant in the solar system.
AB  - Ever since Pluto lost its status as one of the main planets of our solar system
      and was demoted to just another frozen denizen of the Kuiper belt, we have had to
      make do with eight, albeit in a pleasing symmetry, with four rocky ones this side
      of the asteroid belt and four giants on the far side. Now it looks like number
      nine is back on the slate: the existence of a large planet, about ten times as
      massive as Earth and hundreds of times more distant from the Sun than Earth
      itself, has been postulated to explain the curiously bunched-up orbits of several
      small celestial bodies, far beyond the orbit of Neptune. To date, we have only
      "proof by simulation" and we are yet to observe this massive planet in the
      backyard of our solar system by more direct means. However, powerful new
      telescopes should provide visual evidence within the next few decades.

PMID- 28742477
TI  - Science news.

PMID- 28742478
TI  - Toxicological and analytical assessment of e-cigarette refill components on
      airway epithelia.
AB  - There are over 2.6 million users of e-cigarettes in the United Kingdom alone as
      they have been promoted as a safer alternative to traditional cigarettes. The
      addition of flavours and aromas has also proven to be popular with younger
      generations. In this review, we survey the range of studies in the short
      timeframe since e-cigarettes reached the market to draw attention to the health
      associated risks and benefits of their introduction. We complement this review
      with a case study reporting on the composition of selected e-cigarette refills
      with particular emphasis on the toxicological activity of its components on lung
      cells.

PMID- 28742479
TI  - Understanding and combating resistance to online learning.
AB  - Resistance to change is an easy thing for human beings to understand. It is at
      the heart of our desire to find comfort with the familiar such as family, friends
      and our homes. We create homes that are designed a certain way and usually are
      slow to change. We make friends for years and keep those memories etched in
      stone, even though time and age create a romanticised version of the past. Change
      scares us so much that we reflect on our past, the old days, with such reverence
      that we paint over the ugly parts. However, we still talk about how change is
      good. Consider our institutionalised method of learning that has existed for
      centuries and involved people sitting learning from another person in a physical
      space. Then, suddenly in the last 20 years, there is a complete change and almost
      every major institution in the United States and many around the world decided to
      offer a new method of learning. Enter online learning. It becomes a sudden
      disruption to a traditional system. It is not surprising that there has been
      resistance from faculty, students and administrators. Even in the face of
      evidence that online learning works as effectively as traditional onsite
      learning, still people resist. Oddly enough, the resistance can come from those
      who base their careers on facts and research, but continue to ignore the
      evidence. Even performance results get ignored. While this article will address
      the source of resistance to online learning, it will focus primarily on how to
      combat this resistance within an organisation or institution.

PMID- 28742480
TI  - From Caa-ehe to a commercial sweetener - the diterpenoid glycosides of Stevia
      rebaudiana.
AB  - The isolation, structure elucidation, chemistry, biosynthesis and biological
      activity of the sweet steviol glycosides from Stevia rebaudiana, are reviewed.

PMID- 28742481
TI  - The interplay between DNA topology and accessory factors in site-specific
      recombination in bacteria and their bacteriophages.
AB  - Site-specific recombination is employed widely in bacteria and bacteriophage as a
      basis for genetic switching events that control phenotypic variation. It plays a
      vital role in the life cycles of phages and in the replication cycles of
      chromosomes and plasmids in bacteria. Site-specific recombinases drive these
      processes using very short segments of identical (or nearly identical) DNA
      sequences. In some cases, the efficiencies of the recombination reactions are
      modulated by the topological state of the participating DNA sequences and by the
      availability of accessory proteins that shape the DNA. These dependencies link
      the molecular machines that conduct the recombination reactions to the
      physiological state of the cell. This is because the topological state of
      bacterial DNA varies constantly during the growth cycle and so does the
      availability of the accessory factors. In addition, some accessory factors are
      under allosteric control by metabolic products or second messengers that report
      the physiological status of the cell. The interplay between DNA topology,
      accessory factors and site-specific recombination provides a powerful
      illustration of the connectedness and integration of molecular events in
      bacterial cells and in viruses that parasitise bacterial cells.

PMID- 28742482
TI  - Plasmonic nanoparticles and solar cells.

PMID- 28742484
TI  - The 2016 Nobel Prize for Chemistry, awarded for: "The Design and Synthesis of
      Molecular Machines".

PMID- 28742483
TI  - Genetically modified algae produce hydrogen biofuel at five times their normal
      yield.

PMID- 28742485
TI  - A new morphological trait in forensic identification - middle phalangeal hair
      (MPH).
AB  - Middle phalangeal hairs (MPH) are present on the dorsal aspect of the middle
      phalange of the fingers except for the thumb. The MPH have been of interest to
      anthropologists, human biologists, clinicians, geneticists and anatomists in the
      past as a morphological trait of the human body. The anthropological value of MPH
      is well established in studying population variations, with implications for age,
      ancestry and sex differences. We are of the opinion that MPH may be used
      significantly for forensic identification purposes along with other morphological
      characteristics of the human body. MPH can be one of the individualistic features
      in comparing the ante-mortem and post-mortem records in mass fatality incidents
      and in establishing identity in forensic casework pertaining to CCTV images of
      the hand.

PMID- 28742486
TI  - 'New Life Sciences: The Road Ahead' Report on the BioVisionAlexandria 2016
      Conference.
AB  - The Bibliotheca Alexandrina (BA) has organised its eighth international biennial
      conference, BioVisionAlexandria (BVA) 2016 on 12-14 April 2016 in Alexandria,
      Egypt. The theme of BVA 2016 was 'New Life Sciences: The Road Ahead', where
      cutting-edge relevant research topics at the forefront of science were presented
      by a variety of world-wide renowned speakers. BVA 2016 hosted around 2000
      participants and speakers of diverse backgrounds, creating a multi-disciplinary
      arena for dialogue to explore the opportunities, benefits, and controversial
      threats.

PMID- 28742487
TI  - Decomposition for decarbonisation: evaluation of decarbonisation programmes.
AB  - The Kaya Identity has long been used as a simple yet rigorous way to assess
      options in energy and climate policy. Its shortcoming is that it fails to address
      the very wide range of non-energy factors. This paper presents a simple extension
      of the Kaya Identity - the Emissions Quantification Tool or EQT - that
      incorporates the missing factors while retaining the mathematical transparency of
      the original. The tool allows national policies to be analysed and compared with
      international standards for allowable quotas, from which shortfalls or 'carbon
      debts' can be calculated. It can be used to represent almost any conceivable
      decarbonisation programme, testing assumptions and revealing necessary rates of
      change. The paper demonstrates the use of the tool by analysing prevailing UK
      policy and variant scenarios. The results are often surprising.

PMID- 28742489
TI  - DIY Biology - hacking goes viral!
AB  - The D-It-Yourself Biology (DIYBio) movement has gained significant traction in
      recent years; morphing from counter culture to an essential component of
      biology's future development.

PMID- 28742488
TI  - Side-chain liquid crystal conducting polymers.
AB  - This article overviews some of the research progress on the effects of
      incorporating liquid crystalline functionalities into commercial conjugated
      polymers such as polythiophene, polypyrrole and polyaniline. Polarisable aromatic
      mesogens are generally attached via a flexible spacer group to the monomers to
      form a side-chain. Consequently, the selforganising properties of liquid crystals
      can be used to influence the conducting polymer backbone and control the
      electrical, magnetic and mechanical properties of the material. Some applications
      of these interesting materials are discussed.

PMID- 28742490
TI  - Observing and understanding the ultrafast photochemistry in small molecules:
      applications to sunscreens.
AB  - In this review, we discuss the importance of biological and artificial
      photoprotection against overexposure to harmful ultraviolet radiation. Transient
      electronic and transient vibrational absorption spectroscopies are highlighted as
      important tools in understanding the energy transfer in small molecules, with a
      focus on the application to commercial sunscreens with representative examples
      given. Oxybenzone, a common ingredient in commercial sunscreens and sinapoyl
      malate, a biological sunscreen in plant leaves are presented as case studies.

PMID- 28742491
TI  - The canary in the coalmine; bee declines as an indicator of environmental health.
AB  - Bee declines have received much attention of late, but there is considerable
      debate and confusion as to the extent, significance and causes of declines. In
      part, this reflects conflation of data for domestic honeybees, numbers of which
      are largely driven by economic factors, with those for wild bees, many of which
      have undergone marked range contractions but for the majority of which we have no
      good data on population size. There is no doubt that bees are subject to numerous
      pressures in the modern world. The abundance and diversity of flowers has
      declined along with availability of suitable nest sites, bees are chronically
      exposed to cocktails of agrochemicals, and they are simultaneously exposed to
      novel parasites and pathogens accidentally spread by humans. Climate change is
      likely to exacerbate these problems in the future, particularly for cool- climate
      specialists such as bumblebees. Stressors do not act in isolation; for example
      pesticide exposure can impair both detoxification mechanisms and immune
      responses, rendering bees more susceptible to parasites. It seems certain that
      chronic exposure to multiple, interacting stressors is driving honeybee colony
      losses and declines of wild pollinators. Bees have a high profile and so their
      travails attract attention, but these same stressors undoubtedly bear upon other
      wild organisms, many of which are not monitored and have few champions. Those
      wild insects for which we do have population data (notably butterflies and moths)
      are overwhelmingly also in decline. We argue that bee declines are indicators of
      pervasive and ongoing environmental damage that is likely to impact broadly on
      biodiversity and the ecosystem services it provides.

PMID- 28742492
TI  - From 'mad honey' to hypotensive agents, the grayanoid diterpenes.
AB  - The toxicity of Rhododendron species and other members of the Ericaceae which is
      due to the grayanoid diterpenes, is described. Their structures, biogenesis and
      biological activity is reviewed.

PMID- 28742493
TI  - Current Commentary Recent Developments in Solar Energy Applications based on
      Perovskites: A Current Commentary.

PMID- 28742495
TI  - Science news: Atomic Level Data Storage.

PMID- 28742496
TI  - Experience-dependent shaping of hippocampal CA1 intracellular activity in novel
      and familiar environments.
AB  - The hippocampus is critical for producing stable representations of familiar
      spaces. How these representations arise is poorly understood, largely because
      changes to hippocampal inputs have not been measured during spatial learning.
      Here, using intracellular recording, we monitored inputs and plasticity-inducing
      complex spikes (CSs) in CA1 neurons while mice explored novel and familiar
      virtual environments. Inputs driving place field spiking increased in amplitude -
      often suddenly - during novel environment exploration. However, these increases
      were not sustained in familiar environments. Rather, the spatial tuning of inputs
      became increasingly similar across repeated traversals of the environment with
      experience - both within fields and throughout the whole environment. In novel
      environments, CSs were not necessary for place field formation. Our findings
      support a model in which initial inhomogeneities in inputs are amplified to
      produce robust place field activity, then plasticity refines this representation
      into one with less strongly modulated, but more stable, inputs for long-term
      storage.

PMID- 28742497
TI  - Causal role for the subthalamic nucleus in interrupting behavior.
AB  - Stopping or pausing in response to threats, conflicting information, or surprise
      is fundamental to behavior. Evidence across species has shown that the
      subthalamic nucleus (STN) is activated by scenarios involving stopping or
      pausing, yet evidence that the STN causally implements stops or pauses is
      lacking. Here we used optogenetics to activate or inhibit mouse STN to test its
      putative causal role. We first demonstrated that optogenetic stimulation of the
      STN excited its major projection targets. Next we showed that brief activation of
      STN projection neurons was sufficient to interrupt or pause a self-initiated bout
      of licking. Finally, we developed an assay in which surprise was used to
      interrupt licking, and showed that STN inhibition reduced the disruptive effect
      of surprise. Thus STN activation interrupts behavior, and blocking the STN blunts
      the interruptive effect of surprise. These results provide strong evidence that
      the STN is both necessary and sufficient for such forms of behavioral response
      suppression.

PMID- 28742499
TI  - How should novelty be valued in science?
AB  - Scientists are under increasing pressure to do "novel" research. Here I explore
      whether there are risks to overemphasizing novelty when deciding what constitutes
      good science. I review studies from the philosophy of science to help understand
      how important an explicit emphasis on novelty might be for scientific progress. I
      also review studies from the sociology of science to anticipate how emphasizing
      novelty might impact the structure and function of the scientific community. I
      conclude that placing too much value on novelty could have counterproductive
      effects on both the rate of progress in science and the organization of the
      scientific community. I finish by recommending that our current emphasis on
      novelty be replaced by a renewed emphasis on predictive power as a characteristic
      of good science.

PMID- 28742498
TI  - Subthalamic nucleus gamma activity increases not only during movement but also
      during movement inhibition.
AB  - Gamma activity in the subthalamic nucleus (STN) is widely viewed as a pro-kinetic
      rhythm. Here we test the hypothesis that rather than being specifically linked to
      movement execution, gamma activity reflects dynamic processing in this nucleus.
      We investigated the role of gamma during fast stopping and recorded scalp
      electroencephalogram and local field potentials from deep brain stimulation
      electrodes in 9 Parkinson's disease patients. Patients interrupted finger tapping
      (paced by a metronome) in response to a stop-signal sound, which was timed such
      that successful stopping would occur only in ~50% of all trials. STN gamma (60-90
      Hz) increased most strongly when the tap was successfully stopped, whereas phase
      based connectivity between the contralateral STN and motor cortex decreased. Beta
      or theta power seemed less directly related to stopping. In summary, STN gamma
      activity may support flexible motor control as it did not only increase during
      movement execution but also during rapid action-stopping.

PMID- 28742500
TI  - Adverse effects of androgen deprivation therapy in patients with prostate cancer:
      focus on metabolic complications.
AB  - Prostate cancer is the most common cancer among men and androgen deprivation
      therapy (ADT) is the most effective treatment for this disease. The cornerstone
      of the treatment of prostate cancer is inhibition of testosterone production
      which interrupts testosterone-induced growth of the prostate tumor. The dramatic
      decrease in testosterone levels, however, has several undesirable effects on the
      metabolic profile and bone metabolism and can also lead to fatigue, loss of
      libido, gynecomastia, and anemia, provoke vasomotor flushing, and generally
      affect the quality of life. Due to the long-term survival rates of patients with
      prostate cancer, treatment-related adverse effects are highly relevant and thus,
      in each clinical setting, the benefits of ADT must be weighed against treatment
      related adverse effects. The current review focuses on the more recently
      described metabolic complications of androgen deprivation therapy, including
      obesity, diabetes, lipid alterations, metabolic syndrome, and cardiovascular
      disease. In addition, it provides practical management recommendations drawn from
      the available guidelines issued by the American Diabetes Association and American
      Heart Association.

PMID- 28742501
TI  - Novel insights into the molecular mechanisms underlying generalized
      glucocorticoid resistance and hypersensitivity syndromes.
AB  - Glucocorticoids play a fundamental role in many physiologic functions and
      contribute substantially to the achievement of homeostasis. These pleiotropic
      glucocorticoid actions are mediated by a ubiquitously expressed transcription
      factor, the human glucocorticoid receptor (hGR), which may influence the
      transcription rate of numerous target genes, interact with other transcription
      factors, trigger the activation of several kinase pathways or modulate
      mitochondrial DNA expression. Any genetic defects in the NR3C1gene that encodes
      the hGR may cause Primary Generalized Glucocorticoid Resistance or
      Hypersensitivity Syndromes, two rare allostatic endocrinologic conditions
      characterized by partial impaired tissue sensitivity to glucocorticoids. However,
      there are patients who present with clinical manifestations suggestive of the
      above syndromes and do not harbor an inactivating or activating point mutation,
      insertion or deletion in the NR3C1gene. In these cases, several other factors
      might influence the glucocorticoid signal transduction. In this review, we
      discuss the numerous glucocorticoid functions and the multiple hGR isoforms, we
      present the genomic, nongenomic and mitochondrial glucocorticoid signaling
      cascade and we summarize the clinical manifestations and pathogenesis of Primary
      Generalized Glucocorticoid Resistance or Hypersensitivity Syndromes. Finally, we
      speculate that the next generation sequencing technologies will undoubtedly
      enable us to gain a deeper understanding of the GR "interactome".

PMID- 28742502
TI  - Temozolomide therapy for resistant prolactin-secreting pituitary adenomas and
      carcinomas: a systematic review.
AB  - Pituitary tumors represent 10-15% of all intracranial tumors; of these,
      prolactinomas account for 40-50% of cases. Prolactinomas usually respond well to
      dopamine agonists (DA) as first-line therapy. However, treatment resistance
      remains a concern. Temozolomide (TMZ) is an oral alkylating agent that has shown
      promise in treating aggressive pituitary adenomas and carcinomas that are
      resistant to other therapies. To date, no control trials have been undertaken and
      only single case reports of pituitary tumors treated with TMZ have been
      published. A systematic literature search was conducted for studies reporting the
      use of TMZ for the treatment of prolactinomas that were resistant to standard
      therapy. In total, 42 reported cases were identified and included in our
      analysis: 23 cases of prolactin-secreting adenomas and 19 of prolactin-secreting
      carcinomas. Prior to TMZ administration, patients had exhibited tumor progression
      and had previously undergone various treatments including surgery, radiotherapy,
      and drug therapy. Tumor shrinkage was reported in 76% of patients. Reduced
      prolactin levels were observed in 75% of patients, while normalization of
      prolactin was reported in 8%. TMZ failure occurred in 20.6% of cases. Most
      patients exhibited no serious adverse effects. In conclusion, TMZ has potential
      for the treatment of highly aggressive and resistant prolactin-secreting adenomas
      and carcinomas, as demonstrated by tumor shrinkage or complete response and
      normalization of hormone hypersecretion, and exhibits good tolerability and few
      side effects.

PMID- 28742503
TI  - PTH and PTHR1 in osteocytes. New insights into old partners.
AB  - Parathyroid hormone receptors are present in bone cells and play a crucial role
      in the maintenance of skeletal integrity, bone homeostasis and regulation of
      calcium and phosphate metabolism. Although the function of these receptors has
      long being recognized in the cells of the osteoblastic lineage regulating
      directly osteoblast differentiation and function and indirectly
      osteoclastogenesis, recent findings demonstrate their functional presence in
      osteocytes participating in the co-ordination of bone remodelling. In this review
      we focus on the key roles of these receptors in osteoblasts and osteocytes,
      combining what is known and what is new regarding these interesting pleiotropic
      hormone receptors.

PMID- 28742504
TI  - Correlation of serum anti-Mullerian hormone levels with positive in vitro
      fertilization outcome using a short agonist protocol.
AB  - OBJECTIVE: We examined the predictive ability of anti-Mullerian hormone (AMH) for
      clinical pregnancy in women who underwent in vitro fertilization (IVF) cycles in
      a short agonist protocol. DESIGN: This is a retrospective cohort study of 222
      women undergoing their first IVF attempt between June 2010 and March 2016.
      Multivariate logistic regression analysis was performed to evaluate the
      independent associations between clinical pregnancy and its possible predictors.
      RESULTS: 14.9% of cycles were cancelled, >3 oocytes were retrieved in 55.4% of
      cycles and embryo transfer was performed in 70.7% of cases. Live birth was the
      final outcome in 19.8% of subjects, miscarriage occurred in 4.1%, whereas no
      pregnancy occurred in the remaining 76.1% of the study sample. The number of
      oocytes, number of embryos, embryo transfer rate and pregnancy rates were
      positively associated with serum AMH concentrations (p <0.001, for each
      association). When analyzed by age quartiles, the overall association between AMH
      and clinical pregnancy rates was evident across all age strata. CONCLUSIONS:
      Serum AMH levels are a strong predictive marker of clinical pregnancy in women
      undergoing a short agonist IVF protocol. There is also a strong association with
      cancellation rate, number of oocytes retrieved, poor response (<=3 oocytes),
      number of embryos, embryo transfer rate and live birth rates.

PMID- 28742505
TI  - Effects of a hops (Humulus lupulus L.) dry extract supplement on self-reported
      depression, anxiety and stress levels in apparently healthy young adults: a
      randomized, placebo-controlled, double-blind, crossover pilot study.
AB  - OBJECTIVE: The Humulus lupulus L. plant (hops) is used as a herbal medicinal
      product for anxiety/mood disorders. Our aim was to study the effects of a hops
      dry extract on self-reported depression, anxiety and stress levels in young
      adults. DESIGN: Apparently healthy young adults from our university completed the
      Depression Anxiety Stress Scale-21 (DASS-21) and those reporting at least mild
      depression, anxiety and stress were invited to complete the study intervention.
      This followed a randomized (1:1), placebo-controlled, double-blind, crossover
      design with two 4-week intervention periods (Melcalin hops or placebo; two 0.2 gr
      capsules once daily) separated by a 2-week wash-out. Anthropometric measurements,
      DASS-21 assessments and measurements of morning cortisol plasma levels were
      performed at the beginning and the end of the 4-week treatment periods. RESULTS:
      36 participants (Females/Males: 31/5; age: 24.7+/-0.5 years) completed the study
      intervention (attrition: 6/42). No significant changes in body weight and
      composition or morning circulating cortisol were noted with the hops or placebo.
      Significantly decreased DASS-21 anxiety, depression and stress scores were
      documented with hops (9.2+/-7.3 vs. 5.1+/-5.9, 11.9+/-7.9 vs. 9.2+/-7.4, and
      19.1+/-8.1 vs. 11.6+/-8.1; all p values <0.05), which were significantly greater
      compared to those caused by the placebo (all p values <0.05). CONCLUSION: In
      otherwise healthy young adults reporting at least mild depression, anxietyand
      stress symptoms, daily supplementation with a hops dry extract can significantly
      improve all these symptoms over a 4-week period. These beneficial effects agree
      with the indication of hops for anxiety/mood disorders and restlessness, as
      approved by the German Commission E.

PMID- 28742506
TI  - Bioimpedance analysis vs. DEXA as a screening tool for osteosarcopenia in lean,
      overweight and obese Caucasian postmenopausal females.
AB  - BACKGROUND-OBJECTIVES: We aimed at evaluating the efficiency of a newly
      developed, advanced Bioimpedance Analysis (BIA-ACC(r)) device as a screening tool
      for determining the degree of obesity and osteosarcopenia in postmenopausal women
      with normal or decreased bone density determined by Dual-Energy X-Ray
      absorptiometry (DEXA) in a representative sample of Greek postmenopausal women.
      METHODS: This is a single-gate cross-sectional study of body composition measured
      by BIA-ACC(r) and DEXA. Postmenopausal females with BMI ranging from 18.5 to 40
      kg/m2 were subjected to two consecutive measurements of DEXA and BIA-ACC(r)
      within 5-10 minutes of each other. We used Pearson's co-efficient to examine
      linear correlations, the intraclass correlation co-efficient (ICC) to test
      reliability, Bland-Atman plots to assess bias and Deming regressions to establish
      the agreement in parameters measured by BIA-ACC(r) and DEXA. Last, we used ANOVA,
      with Bonferroni correction and Dunnett T3 post hoc tests, for assessing the
      differences between quantitative and Pearson's x2 between qualitative variables.
      SAMPLE AND RESULTS: Our sample consisted of 84 overweight/obese postmenopausal
      women, aged 39-83 years, of whom 22 had normal bone density, 38 had osteopenia
      and 24 had osteoporosis based on DEXA measurements, using quota sampling. ICCs
      and Deming regressions showed strong agreement between BIA-ACC(r) and DEXA and
      demonstrated minimal proportional differences of no apparent clinical
      significance. Bland-Altman plots indicated minimal biases. Fat, skeletal and bone
      mass measured by BIA-ACC(r) and DEXA were increased in the non-osteopenic/non
      osteoporotic women compared with those of the osteopenic and osteoporotic groups.
      CONCLUSIONS: BIA-ACC(r) is a rapid, bloodless and useful screening tool for
      determining body composition adiposity and presence of osteo-sarcopenic features
      in postmenopausal women. Women with osteopenia and osteoporosis evaluated by DEXA
      had decreased fat, skeletal and bone mass compared with normal bone density
      women, suggesting concordance in the change of these three organ masses in
      postmenopausal women.

PMID- 28742507
TI  - Severe neurological abnormalities in a young boy with impaired thyroid hormone
      sensitivity due to a novel mutation in the MCT8 gene.
AB  - Monocarboxylate transporter 8 (MCT8) is an active and specific thyroid hormone
      transporter into neurons. MCT8 mutations cause an X-linked condition known as
      Allan-Herndon-Dudley syndrome and are characterized by impaired psychomotor
      development and typical abnormal thyroid function. We describe a 10-year-old boy
      with severe cognitive disability, axial hypotonia, spastic quadriplegia and
      sporadic dyskinetic episodes. He initially presented with thyroid dysfunction
      (high FT3, low rT3, low FT4 and normal TSH) and generalized retardation of the
      cerebral and cerebellar myelination in brain magnetic resonance imaging. The
      clinical and laboratory findings led to sequencing of the SLC16A2/MCT8 gene,
      which identified a novel missense mutation in exon 5. The study of peripheral
      markers of thyroid function suggests a paradoxical state of thyrotoxicosis in
      some peripheral tissues. Our patient had a typical clinical presentation at birth
      but because of the rarity of his disease his diagnosis was not made until the age
      of 7. The delay can also be explained by the omission of the free T3 assay in the
      first thyroid evaluation performed. This case therefore highlights the possible
      benefit of including the T3 assay in the study of patients with severe
      psychomotor disability of unknown etiology, thus eliminating extra costs for
      unnecessary complementary diagnostic tests.

PMID- 28742508
TI  - Clinical characterization of a novel calcium sensing receptor genetic alteration
      in a Greek patient with autosomal dominant hypocalcemia type 1.
AB  - OBJECTIVE: Autosomal dominant hypocalcemia (ADH) is a rare familial or sporadic
      syndrome associated with activating mutations in the calcium sensing receptor
      (CaSR) gene. The aim of this study was to assess the functional significance of a
      novel CaSR mutation and, moreover, to present the clinical characteristics and
      the bone mineral density (BMD) progression from early childhood to late puberty
      in a patient with ADH. DESIGN: Genetic analysis of the CaSR gene was performed in
      a patient who presented in the neonatal period with hypocalcemic seizures and
      biochemical features of ADH. The functional impact of the novel mutation
      identified was assessed in cultured HEK 293T cells, transfected with either the
      wild type (WT) or mutant CaSR, by evaluating intracellular calcium ([Ca2+]i)
      influx after stimulation with extracellular calcium (Ca2+). Several BMD
      measurements were performed during the patient's follow-up until late puberty.
      RESULTS: A novel CaSR mutation (p.L123S) was identified, which, as demonstrated
      by functional analysis, renders CaSR more sensitive to extracellular changes of
      Ca2+ compared with the WT, although the difference is not statistically
      significant. BMD measurements, from early childhood to late puberty, revealed
      high normal to elevated BMD. CONCLUSION: We present the first Greek patient, to
      our knowledge, with sporadic ADH due to a novel gain-of-function mutation of the
      CaSR gene.

PMID- 28742509
TI  - Persistent Mullerian duct syndrome: A novel mutation in the Alphanti-Mullerian
      Etaormone gene.
AB  - BACKGROUND AND OBJECTIVE: Persistent Mullerian duct syndrome (PMDS) is a
      relatively rare form of 46,XY disorder of sex development caused by the failure
      of formation, release or action of anti-Mullerian hormone (AMH) in intrauterine
      life. In this report we describe a case diagnosed with PMDS with a novel
      homozygous mutation in the AMH gene. CASE REPORT: A 4-month-old male presented
      with bilateral cryptorchidism and normal external genitalia. The laboratory
      examination revealed normal gonadotropin levels for his age (FSH: 0.91 mIU/mL,
      LH: 1.23 mIU/mL, testosteron <0.13 ng/mL, respectively). AMH was undetectable
      (<0.01 ng/mL). Ultrasonography (USG) revealed absence of the left gonad and an
      intraabdominally located right gonad. Laparoscopy demonstrated the presence of a
      rudimentary uterus and fallopian tubes. Karyotyping revealed a normal 46,XY
      karyotype. Molecular genetic analysis demonstrated a novel homozygous mutation
      [p.C526F (c.1577G>T)] in the AMH gene. CONCLUSION: PMDS should be kept in mind in
      all cases with bilateral crytorchidism. Orchidopexy and resection of Mulletian
      duct derivates, exercising extra caution with regard to maintaining vascular
      supply to the testis, is the recommended approach.

PMID- 28742510
TI  - Congenital nephrogenic diabetes insipidus in the Corpus Hippocraticum: The first
      description.

PMID- 28742511
TI  - Melampus and the cure of Proetus' daughters.

PMID- 28742512
TI  - The sphingomyelin synthase family: proteins, diseases, and inhibitors.
AB  - Sphingomyelin (SM) is among the most important biomolecules in eukaryotes and
      acts as both constructive components and signal carrier in physiological
      processes. SM is catalyzed by a membrane protein family, sphingomyelin synthases
      (SMSs), consisting of three members, SMS1, SMS2 and SMSr. SMSs modulate
      sphingomyelin and other sphingolipids levels, thereby regulating membrane
      mobility, ceramide-dependent apoptosis and DAG-dependent signaling pathways. SMSs
      was found associated with various diseases. Downregulation of SMS2 activity
      results in protective effects against obesity, atherosclerosis and diabetes and
      makes SMS2 inhibitors potential medicines. Structural guided specific drug design
      could be the next breakthrough, discriminating SMS2 from other homologs.

PMID- 28742513
TI  - Kallistatin: double-edged role in angiogenesis, apoptosis and oxidative stress.
AB  - Kallistatin, via its two structural elements - an active site and a heparin
      binding domain - displays a double-edged function in angiogenesis, apoptosis and
      oxidative stress. First, kallistatin has both anti-angiogenic and pro-angiogenic
      effects. Kallistatin treatment attenuates angiogenesis and tumor growth in cancer
      bearing mice. Kallistatin via its heparin-binding site inhibits angiogenesis by
      blocking vascular endothelial growth factor (VEGF)-induced growth, migration and
      adhesion of endothelial cells. Conversely, kallistatin via the active site
      promotes neovascularization by stimulating VEGF levels in endothelial progenitor
      cells. Second, kallistatin inhibits or induces apoptosis depending on cell types.
      Kallistatin attenuates organ injury and apoptosis in animal models, and its
      heparin-binding site is essential for blocking tumor necrosis factor (TNF)-alpha
      induced apoptosis in endothelial cells. However, kallistatin via its active site
      induces apoptosis in breast cancer cells by up-regulating miR-34a and down
      regulating miR-21 and miR-203 synthesis. Third, kallistatin can act as an
      antioxidant or pro-oxidant. Kallistatin treatment inhibits oxidative stress and
      tissue damage in animal models and cultured cells. Kallistatin via the heparin
      binding domain antagonizes TNF-alpha-induced oxidative stress, whereas its active
      site is crucial for stimulating antioxidant enzyme expression. In contrast,
      kallistatin provokes oxidant formation, leading to blood pressure reduction and
      bacterial killing. Kallistatin-mediated vasodilation is partly mediated by H2O2,
      as the effect is abolished by the antioxidant enzyme catalase. Moreover,
      kallistatin exerts a bactericidal effect by stimulating superoxide production in
      neutrophils of mice with microbial infection as well as in cultured immune cells.
      Thus, kallistatin's dual roles in angiogenesis, apoptosis and oxidative stress
      contribute to its beneficial effects in various diseases.

PMID- 28742514
TI  - The importance of biochemical and genetic findings in the diagnosis of atypical
      Norrie disease.
AB  - BACKGROUND: Norrie disease (ND) is a rare X-linked disorder characterized by
      bilateral congenital blindness. ND is caused by a mutation in the Norrie disease
      pseudoglioma (NDP) gene, which encodes a 133-amino acid protein called norrin.
      Intragenic deletions including NDP and adjacent genes have been identified in ND
      patients with a more severe neurologic phenotype. We report the biochemical,
      molecular, clinical and radiological features of two unrelated affected males
      with a deletion including NDP and MAO genes. METHODS: Biochemical and genetic
      analyses were performed to understand the atypical phenotype and radiological
      findings. Biogenic amines in cerebrospinal fluid (CSF) were measured by high
      performance liquid chromatography. The coding exons of NDP gene were amplified by
      polymerase chain reaction. Multiplex ligation-dependent probe amplification and
      chromosomal microarray were carried out on both affected males. Computed
      tomography and magnetic resonance imaging were performed on the two patients.
      RESULTS: In one patient, the serotonin and catecholamine metabolite levels in CSF
      were virtually undetectable. In both patients, genetic studies revealed
      microdeletions in the Xp11.3 region, involving the NDP, MAOA and MAOB genes.
      Radiological examination demonstrated brain and cerebellar atrophy. CONCLUSIONS:
      We suggest that alterations caused by MAO deficit may remain during the first
      years of life. Clinical phenotype, biochemical findings and neuroimaging can
      guide the genetic study in patients with atypical ND and help us to a better
      understanding of this disease.

PMID- 28742515
TI  - Do exercises improve back pain in pregnancy?
AB  - Objective To assess the efficacy of an exercise program towards reducing back
      pain in pregnant women. Methods In this prospective control study, 145 low risk
      pregnant women who scored more than 20 for functional limitation assessment were
      recruited. The severity of back pain was assessed using the visual analoque scale
      (VAS) and the functional limitation was assessed using the Oswestry disability
      questionnaire (ODQ). All participants were informed of back care measures and
      provided with Paracetamol as an adjunct analgesia. The intervention group will
      have a session with a trained physiotherapist. Subsequently, all participants
      will be required to fill in a similar questionnaire regarding pain intensity and
      functional limitation assessment after 6 weeks post-intervention. Results There
      was a significant reduction in the VAS score and improvement in functional ODQ
      score in the intervention group. The median usage of Paracetamol as an analgesia
      to control back pain in the control group was 500 mg higher than the intervention
      group. There was a weak association of age, parity, duration of back pain, and
      body mass index with functional ODQ score at 6 week following intervention.
      Conclusion The back pain exercise reducing program was effective in reducing back
      pain intensity and analgesia usage with a significant improvement in functional
      ability.

PMID- 28742516
TI  - Prevention of renal ischemia/perfusion-induced renal and hepatic injury in adult
      male Albino rats by oxytocin: role of nitric oxide.
AB  - BACKGROUND: Oxytocin (OT) has an anti-inflammatory and antioxidant effect in the
      different inflammatory models. The current study aimed to evaluate the protective
      function of OT in renal and hepatic damages triggered by renal
      ischemia/reperfusion (IR) in rats. Moreover, the effect of NG-nitro-l-arginine
      methyl ester (l-NAME) was investigated on the kidney and liver functions in renal
      IR model. METHODS: Twenty-four rats were divided into four groups (six rats each)
      as follows: (1) Sham-operated group; (2) Renal IR group; (3) Renal IR+OT group;
      (4) Renal IR+OT+l-NAME. OT (1 mg/kg, i.p.) was administered 30 min prior to the
      induced ischemia and was repeated immediately before the reperfusion period. l
      NAME (10 mg/kg, i.p.) was given 45 min before IR injury. RESULTS: The results
      revealed that OT significantly attenuated the IR-induced elevations in the serum
      urea, creatinine, liver transaminases, and TNF-alpha levels, while nitric oxide
      (NO) and Bcl-2 levels were significantly increased compared with the IR group. OT
      also significantly compensated the decrease in the total antioxidant capacities
      (TAC) and lowered the elevated malondialdehyde (MDA) levels that were observed
      with renal IR in the renal and hepatic tissues. CONCLUSIONS: In conclusion, OT
      ameliorates renal and hepatic damages triggered by renal IR, and this defense
      involves the suppression of inflammation and apoptosis with regulation of oxidant
      antioxidant status. In addition, administration of l-NAME prior to OT partially
      reversed the protective effect of OT ensuring that one of the protective effects
      of OT was through the NO production.

PMID- 28742517
TI  - Type 1 rhizomelic chondrodysplasia punctata with a homozygous PEX7 mutation.
AB  - BACKGROUND: Rhizomelic chondrodysplasia punctata (RCDP) is a rare peroxisomal
      disease characterised by punctate calcifications of non-ossified cartilage
      epiphyseal centres. The main biochemical marker of all RCDP types is a decrease
      in the levels of plasmalogens. Additionally, the accumulation of phytanic acid
      can be used as a differential marker between types of RDCP. Due to the
      biochemical overlap between types 1 and 5 RCDP, a genetic analysis of these genes
      should be performed in patients to identify the type. CASE PRESENTATION: A 2
      month-19-day-old male child presented with symptoms of limited movement and
      discomfort with movement in the extremities. His sister, who had similar clinical
      findings, was diagnosed with tetralogy of Fallot and died at 6 months of age. A
      physical examination revealed an atypical facial appearance, bilateral cataracts,
      sensitivity to touch in the extremities, shortness in the proximal segments of
      the long bones, limited movement in both knees and elbows and axial hypotonicity.
      Laboratory analyses revealed normal ammonia, lactate, plasma and urine amino
      acids, long chain fatty acids and phytanic acid levels. Rhizomelia, significant
      metaphyseal expansion, irregularities in the cortex, loss of ossification,
      fragmented appearance and punctate calcifications in both elbows, both knees and
      in the femoral epiphysis were seen on the skeletal survey. A homozygote p.L70W
      (c.209T>G) mutation was found in the PEX7 gene. CONCLUSIONS: Plasma phytanic acid
      levels can be normal in a patient with type 1 RCDP that develops as a result of a
      PEX7 gene mutation, as in our case. A molecular genetic analysis and/or
      fibroblast culture must be conducted in clinically suspicious cases. While no
      cardiac pathology was found in our case, tetralogy of Fallot was present in his
      sister with similar clinical findings. The presence of different cardiological
      phenotypes in the sibling suggested that the genotype-phenotype correlation may
      not be complete in this disorder.

PMID- 28742518
TI  - Severe hypertriglyceridemia at new onset type 1 diabetes mellitus.
AB  - BACKGROUND: Severe hypertriglyceridemia (HTG) as well as diabetic ketoacidosis
      (DKA) are complications of type 1 diabetes (T1DM). HTG is an exceedingly rare
      complication in the pediatric population and herein we report a case of HTG at
      new-onset T1DM in DKA and discuss management and potential complications. CASE
      PRESENTATION: An 11-year-old previously well patient with a history of fatigue
      and weight loss presented with: glucose >600 mg/dL, venous blood gas: pH 7.26,
      pCO2 20 mmHg, PO2 101 mmHg and base deficit 13 with triglyceride level 3573
      mg/dL. An insulin drip was continued past criteria for discontinuation to
      facilitate lipoprotein lipase-based triglyceride metabolism. CONCLUSIONS: Lipemia
      secondary to severe HTG, though exceedingly rare, may exist in new onset T1DM
      with DKA. Complicating the diagnosis is the possibility of an analytical error
      from lipemia causing incongruence in diagnostic criteria. Clinicians should rely
      on clinical criteria for management and should consider HTG if laboratory data is
      inconsistent with the clinical picture.

PMID- 28742519
TI  - 45,X/46,XY ovotesticular disorder of sex development revisited: undifferentiated
      gonadal tissue may be mistaken as ovarian tissue.
AB  - BACKGROUND: The 45,X/46,XY karyotype has been associated with mixed gonadal
      dysgenesis (MGD) and ovotesticular disorder of sex development (DSD). Our aim was
      to revise the diagnosis of ovotesticular DSD in two patients in the context of a
      retrospective study of 45,X/46,XY subjects with genital ambiguity. CASE
      PRESENTATION: Patient 1 had a left streak gonad; the right one was considered an
      ovotestis. Patient 2 had a right testis; the left gonad was considered an ovary.
      Revision of the histological sections was performed. Both the "ovarian" part of
      the right gonad of patient 1 and the left "ovary" of patient 2 contained ovarian
      type stroma with clusters of sex-cordlike structures and rare germ cells,
      compatible with undifferentiated gonadal tissue (UGT). Misdiagnosis of ovarian
      tissue in patients with 45,X/46,XY mosaicism or its variants could also be found
      in six published case reports. CONCLUSIONS: A distinction between 45,X/46,XY
      ovotesticular DSD and MGD should be made on past and future cases keeping in mind
      that UGT may be mistaken as ovarian tissue.

PMID- 28742520
TI  - Growth and pubertal patterns in young survivors of childhood acute lymphoblastic
      leukemia.
AB  - BACKGROUND: Survivors of acute lymphoblastic leukemia (ALL) may experience
      endocrine dysfunction. This study evaluated growth and pubertal patterns in
      survivors of childhood ALL. METHODS: Longitudinal assessment of anthropometric
      measurements and pubertal status was performed in a retrospective cohort of
      survivors (n=183). Median age at last endocrine visit was 16.1 years (range 8.2
      27.6); median follow-up time was 8.7 years (range 3-21.4). RESULTS: Treatment
      with chemotherapy+prophylactic cranial radiation (pCRT, n=29) was associated with
      lower mean height standard deviation score (SDS) than chemotherapy alone (n=154)
      (p=0.001) and higher prevalence of adult short stature (13% vs. 2.2%). Mean age
      at pubertal onset was normal (girls: 10.3+/-1.3 years; boys: 12.0+/-1.3 years).
      Precocious puberty, diagnosed in 8.7% of patients, was more prevalent in pCRT
      treated girls. Rates of overweight and obesity were 22.9% and 9.3%, respectively.
      Predictors of endocrine disorders were pCRT (p=0.031) and female gender
      (p=0.041); of obesity, higher body mass index (BMI)-SDS at diagnosis (p=0.001);
      and of short stature, lower height-SDS at diagnosis (p=0.038). CONCLUSIONS: Most
      childhood ALL survivors given chemotherapy alone attain normal adult height and
      puberty. Childhood ALL survivors are at increased risk of overweight, especially
      those with increased BMI at diagnosis. Clinicians should screen for overweight
      early in survivorship and introduce early interventions.

PMID- 28742521
TI  - Sensitivity and specificity of cystic fibrosis-related diabetes screening
      methods: which test should be the reference method?

PMID- 28742522
TI  - Endocrine aspects in cystic fibrosis.

PMID- 28742523
TI  - Pregnancy outcomes among patients with recurrent pregnancy loss and uterine
      anatomic abnormalities.

PMID- 28742524
TI  - Early postnatal echocardiographic assessment of pulmonary blood flow in newborns
      with congenital diaphragmatic hernia.

PMID- 28742525
TI  - Impact factors on fetal descent rates in the active phase of labor: a
      retrospective cohort study.
AB  - AIM: To assess fetal descent rates of nulliparous and multiparous women in the
      active phase of labor and to evaluate significant impact factors. METHODS: In a
      retrospective cohort study at the University Hospital of Zurich, Switzerland, we
      evaluated 6045 spontaneous vaginal deliveries with a singleton in vertex
      presentation between January 2007 and July 2014 at 34 0/7 to 42 0/7 gestational
      weeks. Median fetal descent rates and their 10th and 90th percentiles were
      assessed in the active phase of labor and different impact factors were
      evaluated. RESULTS: Fetal descent rates are exponentially increasing. Nulliparous
      women have slower fetal descent than multiparous women (P<0.001), ranging from 0
      to 5.81 cm/h and from 0 to 15 cm/h, respectively. The total duration of fetal
      descent in labor is 5.42 h for nulliparous and 2.71 h for multiparous women.
      Accelerating impact factors are a lower fetal station, multiparity, increasing
      maternal weight and fetal occipitoanterior position, whereas epidural anesthesia
      decelerates fetal descent (P<0.001). CONCLUSIONS: Fetal descent is a hyperbolic
      increasing process with faster descent in multiparous women compared to
      nulliparous women, is highly inter individual and is associated with different
      impact factors. The diagnosis of labor arrest or prolonged labor should therefore
      be based on such rates as well as on individual evaluation of every parturient.

PMID- 28742526
TI  - The black soldier fly, Hermetia illucens - a promising source for sustainable
      production of proteins, lipids and bioactive substances.
AB  - The growing demand worldwide for proteins and lipids cannot be met by the
      intensive use of agricultural land currently available. Insect mass cultures as a
      source for proteins and lipids have been in focus for various reasons. An insect
      with many positive properties is the black soldier fly, Hermetia illucens, whose
      larvae could be used for the sustainable production of proteins and lipids.
      Furthermore, the larvae produce bioactive substances which could potentially be
      used for human and animal welfare.

PMID- 28742527
TI  - Biotechnological potential of insect fatty acid-modifying enzymes.
AB  - There are more than one million described insect species. This species richness
      is reflected in the diversity of insect metabolic processes. In particular,
      biosynthesis of secondary metabolites, such as defensive compounds and chemical
      signals, encompasses an extraordinarily wide range of chemicals that are
      generally unparalleled among natural products from other organisms. Insect
      genomes, transcriptomes and proteomes thus offer a valuable resource for
      discovery of novel enzymes with potential for biotechnological applications.
      Here, we focus on fatty acid (FA) metabolism-related enzymes, notably the fatty
      acyl desaturases and fatty acyl reductases involved in the biosynthesis of FA
      derived pheromones. Research on insect pheromone-biosynthetic enzymes, which
      exhibit diverse enzymatic properties, has the potential to broaden the
      understanding of enzyme specificity determinants and contribute to engineering of
      enzymes with desired properties for biotechnological production of FA
      derivatives. Additionally, the application of such pheromone-biosynthetic enzymes
      represents an environmentally friendly and economic alternative to the chemical
      synthesis of pheromones that are used in insect pest management strategies.

PMID- 28742528
TI  - Rare Diseases on the Plastic Surgery In-Service Training Examination.

PMID- 28742529
TI  - Risk factors for early mortality on antiretroviral therapy in advanced HIV
      infected adults.
AB  - BACKGROUND: Many HIV-infected individuals present with advanced HIV disease.
      These patients are at high risk of death after antiretroviral therapy (ART)
      initiation, but risk factors for death in these patients are unclear. METHODS: We
      used data from a multisite randomized trial comparing empiric vs. preventive
      tuberculosis therapy in HIV-infected adults initiating ART with CD4 T-cell counts
      less than 50 cells/MUl to evaluate risk factors for death within 48 weeks after
      ART initiation. Cox proportional hazards models were fit to evaluate
      characteristics present at baseline and at 4 weeks after ART initiation,
      including the week 4 CD4 T-cell response and new opportunistic infections.
      RESULTS: Of 850 enrolled, the median pre-ART CD4 T-cell count was 18 cells/MUl
      and 67 (7.9%) died. Baseline risk factors for death included lymphadenopathy,
      lower CD4 T-cell count, lower serum albumin, high white blood cell count,
      elevated neutrophil percentage, and lower hemoglobin. Among 746 participants with
      data at week 4, the median changes in CD4 T-cell count and viral load for those
      who died (n = 43) vs. survived were 26 vs. 56 cells/MUl and -2.7 vs. -2.7 log10
      copies/ml, respectively. Each 20 cell/MUl lower change in week 4 CD4 T-cell count
      was associated with a 20% increased risk of post week-4 mortality (adjusted
      hazard ratio 1.20, 1.01-1.42, P = .038). CONCLUSION: Evidence of active infection
      and suboptimal immunologic response during the first month of ART are associated
      with death in the first year after ART initiation in those with advanced HIV
      disease taking tuberculosis preventive therapy. Strategies to reduce early
      mortality in this population warrant further investigation.

PMID- 28742530
TI  - I-AIM (Indication, Acquisition, Interpretation, Medical Decision-making)
      Framework for Point of Care Lung Ultrasound.

PMID- 28742531
TI  - Variable-Volume Kinetic Model to Estimate Absolute Blood Volume in Patients on
      Dialysis Using Dialysate Dilution.
AB  - Long- and short-term adverse outcomes in hemodialysis (HD) have been associated
      with intradialytic hypotension, a common HD complication and significant cause of
      morbidity. It has been suggested that knowledge of absolute blood volume (ABV)
      could be used to significantly improve treatment outcomes. Different dilution
      based protocols have been proposed for estimating ABV, all relying on the classic
      mono-exponential back-extrapolation algorithm (BEXP). In this paper, we introduce
      a dialysate dilution protocol and an estimation algorithm based on a variable
      volume, two-compartment, intravascular blood water content kinetic model (VVKM).
      We compare ABV estimates derived using the two algorithms in a dialysate dilution
      study including three arterio-venous (AV) and three central-venous (CV) access
      patients, and multiple bolus injection tests (3-5) within each of several (2-6)
      HD treatments. The distribution of differences between ABV estimated from the two
      methods showed negligible systematic difference between the mean values of ABVs
      estimated from the BEXP and VVKM algorithms, however, the VVKM estimates were 53%
      and 42% more precise for the CV and AV patients, respectively. Good agreement was
      observed between measured and VVKM-estimated blood water concentration with the
      root-mean-square error (RMSE) less than 0.02 kg/kg (2%) and 0.03 kg/kg (3%) for
      AV and CV patients, respectively. The dilution protocol and the new VVKM-based
      estimation algorithm offer a noninvasive, inexpensive, safe, and practical
      approach for ABV estimation in routine HD settings.

PMID- 28742532
TI  - Pulmonary Pressure Assessment with the Total Artificial Heart.
AB  - Reversal of pulmonary hypertension has been observed in patients during a bridge
      to transplant with a left ventricular assist device. Total artificial heart (TAH)
      implant prevents subsequent right heart catheterization. Consequently,
      controversy exists over whether the prosthetic right ventricle improves or
      exacerbates pulmonary hypertension. A pulmonary artery (PA) pressure monitor was
      placed in two patients undergoing TAH implant, as a bridge to transplant. One
      patient had pulmonary hypertension at implant; the other had normal pulmonary
      pressures. Daily measurements were taken of systolic, diastolic, and mean PA
      pressures throughout support. Patient 1 received successful transplant after TAH
      support of 91 days. Systolic/diastolic (mean) PA pressures steadily decreased
      from 55/39 (28) mm Hg at implant to 29/18 (7) mm Hg currently. Patient 2 received
      support for 101 days before death due to abdominal ischemic complications.
      Pulmonary arterial pressures stayed consistent throughout this period, from 26/17
      (20) mm Hg at implant to 23/13 (17) mm Hg at the time of death. These findings
      suggest that an implantable PA pressure monitor may be useful in optimizing
      hemodynamics and planning appropriate timing of transplant with TAH support.

PMID- 28742533
TI  - Stripassay Genotyping for the Prediction of the Graft Relative Risk.

PMID- 28742534
TI  - Ultrasound Imaging for Dorsal Ulnar Cutaneous Neuropathy With Extensor Carpi
      Ulnaris Tendinopathy.

PMID- 28742535
TI  - "Anonymous Meltdown": Content Themes Emerging in a Nonfacilitated, Peer-only,
      Unstructured, Asynchronous Online Support Group for Family Caregivers.
AB  - By providing care for loved ones in the home, family caregivers save millions of
      dollars for our overtaxed healthcare system. Support groups can lighten the
      psychological burden of caregiving. Nonprofessionally facilitated (or peer)
      online caregiver support groups can help meet a critical need in healthcare as a
      low-cost resource for caregivers. Online caregiver peer support groups can
      promote the health and well-being of family caregivers and, by extension, the
      patients themselves, resulting in cost-savings for society. A better
      understanding of these types of groups is of critical importance, given the
      unrelenting pace of demographic shift in the United States. The purpose of this
      study was to examine content themes emerging from an unstructured, asynchronous
      online peer support group for family caregivers of people with chronic illness.
      Qualitative content analysis was used, yielding six themes: "experiencing the
      emotional toll," "need for catharsis/venting," "finding the silver linings,"
      "seeking specific advice/problem solving," "realizing home is no longer a haven,"
      and "adapting to the caregiver role." The themes reflect what emerged organically
      in an online support group that was not professionally facilitated or structured
      in any way. Heterogeneity in the relationship between caregivers and care
      recipients may negatively affect outcomes and requires further study.

PMID- 28742536
TI  - Neuroanesthesiology: the ineludible path toward super-specialty.

PMID- 28742537
TI  - Update in Natural Orifice Translumenal Endoscopic Surgery (NOTES).
AB  - PURPOSE OF REVIEW: The recent developments and clinical applications of natural
      orifice translumenal endoscopic surgery (NOTES)-procedures and technologies are
      going to be presented. RECENT FINDINGS: In experimental as well as clinical
      settings, NOTES-procedures are predominantly performed in hybrid technique.
      Current experimental studies focus on the implementation of new surgical
      approaches as well as on the training of procedures. One emphasis in the clinical
      application is transrectal and transanal interventions. Transanal total
      mesorectal excision is equivalent to laparoscopic procedures but with the benefit
      of an even less invasive access. Transvaginal cholecystectomy can achieve results
      that are comparable to surgeries that are performed with laparoscopic techniques
      alone. An analysis of the German NOTES-Register concerning appendectomies as well
      as the national performance of NOTES-interventions in Switzerland is presented.
      Apart from intraabdominal approaches, several centers proclaim transoral
      thyroidectomies and transoral mediastinoscopies. SUMMARY: NOTES-procedures are
      performed in animal experiments as well as in clinical setting although with less
      frequency. At this time, hybrid techniques using rigid instruments are mainly
      applied.

PMID- 28742538
TI  - Anaphylaxis and intimate behaviour.
AB  - PURPOSE OF REVIEW: Intimate behaviours may represent an unusual way of exposure
      to a culprit allergen, or the frame for sex-related allergies due to triggers
      typically linked to that situation. The present review aims at summarizing the
      state of the art about the topic, in order to spread the awareness and the basic
      know-how in the field of sexual-related allergies. RECENT FINDINGS: Kiss-related
      IgE-mediated reactions are caused in sensitized partners mainly by the passive
      transport of allergenic molecules through saliva, skin or oral mucosa. It has
      also been recently suggested that kissing may act as an epicutaneous way for
      induction of allergic sensitization. Among food and drugs, not only but mostly,
      peanuts and beta-lactams, respectively, are the usual trigger. Although
      controversial, 1-hour wait before kissing and a proper mouth cleaning have been
      suggested as prevention strategies. Sexual intercourse related local or systemic
      symptoms can be caused by seminal plasma hypersensitivity, an IgE-mediated/type
      IV reaction due to prostate-specific antigen, which carries high homology to the
      canine prostatic kallikrein (Can f 5). Although applied to few patients,
      successful desensitization and immunotherapy protocols have been proposed.
      SUMMARY: Intimate behaviours are possible modalities of contact with the
      allergen. The exact prevalence of such hypersensitivity reactions is not known,
      but for its implications on Quality of Life and reproductive wishes, the possible
      link between sex and allergy should become part of the personal culture of
      clinical allergists and every clinician, in order to extend and improve the
      diagnosis of unusual or unexplained conditions.

PMID- 28742540
TI  - Comparison of Tissue Yield Using Frictional Fabric Brush Versus Sharp Curettage
      For Endocervical Curettage.
AB  - OBJECTIVE: The aim of the study was to evaluate and compare the diagnostic yield
      of conventional endocervical curettage (ECC) with fabric-based ECC in a
      consistent physician group. MATERIALS AND METHODS: This is a retrospective case
      control study of patients who underwent ECC both before and after introduction of
      a fabric-based ECC device. Histologic examination of curettings was categorized
      as satisfactory, limited, or inadequate. The Kruskall-Wallis test was used to
      compare proportions of gross descriptions and final diagnoses between groups.
      RESULTS: Between January 2010 and July 2011, 9234 ECCs were performed using
      conventional ECC technique. From September 2011 to October 2013, 774 ECCs were
      performed with the fabric-based ECC. Using the conventional ECC technique, 7809
      (84.6%) of specimens were satisfactory, 1037 (11.2%) were limited, and 388 (4.2%)
      were inadequate and repeat biopsy was recommended. With fabric ECC, 705 (91.1%)
      of specimens were satisfactory, 64 (8.3%) were limited, and 5 (0.6%) were
      inadequate, and repeat biopsy was recommended. There were significantly fewer
      inadequate specimens with the fabric-based ECC (4.2% vs 0.6%, p < .001).
      CONCLUSIONS: Fabric-based ECC may significantly decrease inadequate and limited
      ECC specimens.

PMID- 28742539
TI  - Translating evidence into practice in acute respiratory distress syndrome:
      teamwork, clinical decision support, and behavioral economic interventions.
AB  - PURPOSE OF REVIEW: Although the treatment of the acute respiratory distress
      syndrome (ARDS) with low tidal volume (LTV) mechanical ventilation improves
      mortality, it is not consistently administered in clinical practice. This review
      examines strategies to improve LTV and other evidence-based therapies for
      patients with ARDS. RECENT FINDINGS: Despite the well established role of LTV in
      the treatment of ARDS, a recent multinational study suggests it is under-utilized
      in clinical practice. Strategies to improve LTV include audit and feedback,
      provider education, protocol development, interventions to improve ICU teamwork,
      computer decision support, and behavioral economic interventions such as making
      LTV the default-ventilator setting. These strategies typically target all
      patients receiving invasive mechanical ventilation, effectively avoiding the
      problem of poor ARDS recognition in clinical practice. To more effectively
      administer advanced ARDS therapies, such as prone positioning, better approaches
      for ARDS recognition will also be required. SUMMARY: Multiple strategies can be
      utilized to improve adherence to LTV ventilation in ARDS patients.

PMID- 28742541
TI  - Parental Psychological Distress and Family Food Insecurity: Sad Dads in Hungry
      Homes.
AB  - OBJECTIVE: To examine whether household food insecurity is associated with
      serious psychological distress (SPD) in fathers and mothers in a nationally
      representative US sample. METHODS: We analyzed cross-sectional, matched child
      parent data from the 2014 to 2015 National Health Interview Survey (N = 18,456).
      Parental psychological distress was assessed using the Kessler-6 (K-6) scale.
      Family food security was measured using the USDA's 10-item Food Security scale,
      and households were dichotomized as food secure or food insecure. Multivariate
      logistic regression analyses were performed to examine associations between SPD
      and food insecurity stratified by parental status (mother/father), controlling
      for sociodemographic factors. RESULTS: One hundred forty-seven (2.0%) fathers,
      444 (3.9%) mothers, and 591 (3.2%) of all parents had K-6 scores indicating SPD.
      A total of 2414 (13.1%) parents reported being food insecure, including 750
      (10.4%) fathers and 1664 (14.8%) mothers. In multivariate analyses, food
      insecurity was significantly associated with SPD both among fathers and mothers
      (odds ratio [OR] = 4.2; 95% confidence interval [CI], 2.4-7.3 and OR = 2.6; 95%
      CI, 1.9-3.5, respectively). CONCLUSION: This is the first study we are aware of
      to demonstrate that food insecurity is independently associated with SPD among
      fathers and mothers, and that fathers may be at higher risk of SPD than mothers
      in food insecure homes. These findings highlight the need to assess and treat the
      mental health of fathers, a historically underrepresented group in the fields of
      mental health and pediatrics, in addition to mothers, in food insecure homes.

PMID- 28742542
TI  - Clinical Practice Guidelines for Cryosurgery of Pancreatic Cancer: A Consensus
      Statement From the China Cooperative Group of Cryosurgery on Pancreatic Cancer,
      International Society of Cryosurgery, and Asian Society of Cryosurgery.
AB  - Pancreatic cancer (PC), one of the most lethal malignancies, accounts for 8% to
      10% of digestive system cancers, and the incidence is increasing. Surgery,
      chemotherapy, and radiotherapy have been the main treatment methods but are not
      very effective. Cryosurgery was first used in 1984 for treatment of locally
      advanced PC and has since become a considerable treatment for most cases of
      unresectable PC. During the past decade, cryosurgery has been applied in some
      hospitals in China, and the newly developed technique of computed tomography-
      and/or ultrasound-guided percutaneous cryosurgery has shown better results than
      chemotherapy in cases of unresectable locally advanced PC, with the 1-year
      survival rate reported to be more than 50%. To develop standardized criteria for
      the application of cryosurgery in PC, the International Society of Cryosurgery
      and Asian Society of Cryosurgery assembled experts from Austria, Japan, and China
      to discuss treatment methods and arrive at a consensus on the indications,
      contraindications, and preferred techniques of PC cryosurgery.

PMID- 28742543
TI  - One Hundred Twenty-One Resected Solid Pseudopapillary Tumors of the Pancreas: An
      8-Year Single-Institution Experience at Zhongshan Hospital, Shanghai, China.
AB  - OBJECTIVES: The aims of this study were to introduce our experience with treating
      patients with pancreatic solid pseudopapillary tumors (SPTs) and to investigate
      the clinical risk factors for recurrence of SPTs because no consensus has been
      established to date. METHODS: One hundred twenty-one patients underwent surgical
      resection from January 2008 to December 2015 in our institution. Clinical data
      were collected from the standardized reports. RESULTS: Of the 121 patients, 93
      (76.9%) were women, 28 (23.1%) were men, and the mean age at diagnosis was 33.7
      years (range, 11-68 years). Sixty patients were subjected to short-term
      complications, and 8 patients experienced long-term complications, some of whom
      may require surgery. The tumor located in the distal pancreas (P = 0.02), and a
      Ki-67 index value > 1.5 (P = 0.01) indicated malignancy according to the World
      Health Organization 2000 classification. One hundred three patients responded to
      follow-up, and 3 cases (2.9%) were subject to liver metastases. Recurrence was
      more frequently observed in tumors classified as high-grade malignancies
      according to the World Health Organization 2010 classification (P = 0.013),
      synchronous metastases (P < 0.001), peripancreatic fat infiltration (P = 0.018),
      and lymphovascular invasion (P < 0.001). CONCLUSIONS: Evaluating the risk of the
      recurrence of SPTs still requires systematic and multicenter trials in the
      future, even some pathological features showed statistical differences.

PMID- 28742544
TI  - The Marginal Costs of Adverse Drug Events Associated With Exposures to
      Anticoagulants and Hypoglycemic Agents During Hospitalization.
AB  - BACKGROUND: Anticoagulants and hypoglycemic agents are 2 of the most challenging
      drug classes for medical management in the hospital resulting in many adverse
      drug events (ADEs). OBJECTIVE: Estimating the marginal cost (MC) of ADEs
      associated with anticoagulants and hypoglycemic agents for adults in 5 patient
      groups during their hospital stay and the total annual ADE costs for all patients
      exposed to these drugs during their stay. RESEARCH DESIGN AND SUBJECT: Data are
      from 2010 to 2013 Healthcare Cost and Utilization Project (HCUP) State Inpatient
      Databases and Medicare Patient Safety Monitoring System (MPSMS). Deidentified
      patients were linked using probabilistic matching in the same hospital and year
      for 5 patient groups. ADE information was obtained from the MPSMS using
      retrospective structured record review. Costs were derived using HCUP cost-to
      charge ratios. MC estimates were made using Extended Estimating Equations
      controlling for patient characteristics, comorbidities, hospital procedures, and
      hospital characteristics. MC estimates were applied to the 2013 HCUP National
      Inpatient Sample to estimate annual ADE costs. RESULTS: Adjusted MC estimates
      were smaller than unadjusted measures with most groups showing estimates that
      were at least 50% less. Adjusted anticoagulant ADE costs added >45% and
      Hypoglycemic ADE costs added >20% to inpatient costs. The 2013 hospital cost
      estimates for ADEs associated with anticoagulants and hypoglycemic agents were
      >$2.5 billion for each drug class. CONCLUSIONS: This study demonstrates the
      importance of accounting for confounders in the estimation of ADEs, and the
      importance of separate estimates of ADE costs by drug class.

PMID- 28742545
TI  - Reductions in Readmission Rates Are Associated With Modest Improvements in
      Patient-reported Health Gains Following Hip and Knee Replacement in England.
AB  - BACKGROUND: Although many hospital readmission reduction initiatives have been
      introduced globally, health care systems ultimately aim to improve patients'
      health and well-being. We examined whether the hospitals that report greater
      success in reducing readmissions also see greater improvements in patient
      reported outcomes. RESEARCH DESIGN: We examined hospital groups (Trusts) that
      provided hip replacement or knee replacement surgery in England between April
      2010 and February 2013. For each Trust, we calculated risk-adjusted 30-day
      readmission rates from administrative datasets. We also obtained changes in
      patient-reported health between presurgical assessment and 6-month follow-up,
      using general health EuroQuol five dimensions questionaire (EQ-5D) and EuroQuol
      visual analogue scales (EQ-VAS) and procedure-specific (Oxford Hip and Knee
      Scores) measures. Panel models were used to assess whether changes over time in
      risk-adjusted readmission rates were associated with changes over time in risk
      adjusted health gains. RESULTS: Each percentage point reduction in the risk
      adjusted readmission rate for hip replacement was associated with an additional
      health gain of 0.004 for EQ-5D [95% confidence interval (CI), 0.002-0.006], 0.39
      for EQ-VAS (95% CI, 0.26-0.52), and 0.32 for Oxford Hip Score (95% CI, 0.15
      0.27). Corresponding figures for knee replacement were 0.003 for EQ-5D (95% CI,
      0.001-0.004), 0.21 for EQ-VAS (95% CI, 0.12-0.30), and 0.14 in the Oxford Knee
      Score (95% CI, 0.09-0.20). CONCLUSIONS: Reductions in readmission rates were
      associated with modest improvements in patients' sense of their health and well
      being at the hospital group level. In particular, fears that efforts to reduce
      readmission rates have had unintended consequences for patients appear to be
      unfounded.

PMID- 28742546
TI  - Flipping the Objective Structured Clinical Examination: A Teaching Innovation in
      Graduate Nursing Education.
AB  - Objective evaluation of distance-based family nurse practitioner (FNP) students
      can be challenging. One FNP program piloted a teaching innovation, the video
      enhanced objective structured clinical examination (VE-OSCE) or "flip" of the
      traditional face-to-face OSCE, to assess student clinical performance in a
      controlled online environment using a teleconferencing platform. This project
      sought to assess the VE-OSCE design, implementation, and ability to identify FNP
      student learning needs.

PMID- 28742547
TI  - Celiprolol: A Unique Selective Adrenoceptor Modulator.
AB  - Celiprolol is a beta-blocker with a unique pharmacologic profile: it is a beta1
      andrenoceptor antagonist with partial beta2 agonist activity. Given this
      combination of effects, celiprolol may be better described as a selective
      adrenoreceptor modulator. It has antihypertensive and antianginal properties and
      is indicated for those uses in various countries around the world. In the United
      States, however, the proposed indication for this drug will be for the treatment
      of vascular type Ehlers-Danlos syndrome, a rare connective tissue disorder
      characterized by fragile arterial structure and an increased risk of life
      threatening vascular complications. By reducing heart rate and pulsatile
      pressure, celiprolol may reduce the mechanical stress on collagen fibers within
      the arterial wall and be of benefit in patients with vascular type Ehlers-Danlos
      syndrome. The largest investigation of celiprolol in vascular Ehlers-Danlos
      syndrome was prematurely terminated due to significant benefit with celiprolol in
      reducing arterial events in patients with this condition. Celiprolol, therefore,
      represents a beta-blocker that is unique from others in its class in both its
      pharmacology and clinical applications.

PMID- 28742548
TI  - Association Between Survival and Time of Day for Rapid Response Team Calls in a
      National Registry.
AB  - OBJECTIVES: Decreased staffing at nighttime is associated with worse outcomes in
      hospitalized patients. Rapid response teams were developed to decrease
      preventable harm by providing additional critical care resources to patients with
      clinical deterioration. We sought to determine whether rapid response team call
      frequency suffers from decreased utilization at night and how this is associated
      with patient outcomes. DESIGN: Retrospective analysis of a prospectively
      collected registry database. SETTING: National registry database of inpatient
      rapid response team calls. PATIENTS: Index rapid response team calls occurring on
      the general wards in the American Heart Association Get With The Guidelines
      Medical Emergency Team database between 2005 and 2015 were analyzed.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was
      inhospital mortality. Patient and event characteristics between the hours with
      the highest and lowest mortality were compared, and multivariable models
      adjusting for patient characteristics were fit. A total of 282,710 rapid response
      team calls from 274 hospitals were included. The lowest frequency of calls
      occurred in the consecutive 1 AM to 6:59 AM period, with 266 of 274 (97%)
      hospitals having lower than expected call volumes during those hours. Mortality
      was highest during the 7 AM hour and lowest during the noon hour (18.8% vs 13.8%;
      adjusted odds ratio, 1.41 [1.31-1.52]; p < 0.001). Compared with calls at the
      noon hour, those during the 7 AM hour had more deranged vital signs, were more
      likely to have a respiratory trigger, and were more likely to have greater than
      two simultaneous triggers. CONCLUSIONS: Rapid response team activation is less
      frequent during the early morning and is followed by a spike in mortality in the
      7 AM hour. These findings suggest that failure to rescue deteriorating patients
      is more common overnight. Strategies aimed at improving rapid response team
      utilization during these vulnerable hours may improve patient outcomes.

PMID- 28742549
TI  - Readmissions for Recurrent Sepsis: New or Relapsed Infection?
AB  - OBJECTIVES: Sepsis hospitalizations are frequently followed by hospital
      readmissions, often for recurrent sepsis. However, it is unclear how often sepsis
      readmissions are for relapsed/recrudescent versus new infections. The aim of this
      study was to assess the extent to which 90-day readmissions for recurrent sepsis
      are due to infection of the same site and same pathogen as the initial episode.
      DESIGN: Retrospective cohort study. SETTING: University of Michigan Health
      System. PATIENTS: All hospitalizations (May 15, 2013 to May 14, 2015) with a
      principal International Classification of Diseases, Ninth revision, Clinical
      Modification diagnosis of septicemia (038.x), severe sepsis (995.92), or septic
      shock (785.52), as well as all subsequent hospitalizations and sepsis
      readmissions within 90 days. We determined organism and site of sepsis through
      manual chart abstraction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We
      identified 472 readmissions within 90 days of sepsis, of which 137 (29.1%) were
      for sepsis. In sepsis readmissions, the site and organisms were most commonly
      urinary (29.2%), gastrointestinal (20.4%), Gram negative (29.9%), Gram positive
      (16.8%), and culture negative (30.7%). Ninety-four readmissions (68.6%) were for
      infection at the same site as initial sepsis hospitalization. Nineteen percent of
      readmissions were confirmed to be same site and same organism. However,
      accounting for the uncertainty from culture-negative sepsis, as many as 53.2% of
      readmissions could plausibly due to infections with both the same organism and
      same site. CONCLUSIONS: Of the patients readmitted with sepsis within 90 days,
      two thirds had infection at the same site as their initial admission. Just 19%
      had infection confirmed to be from the same site and organism as the initial
      sepsis hospitalization. Half of readmissions were definitively for new
      infections, whereas an additional 34% were unclear since cultures were negative
      in one of the hospitalizations.

PMID- 28742550
TI  - Can Concurrent Abnormalities in Free Light Chains and Immunoglobulin
      Concentrations Identify a Target Population for Immunoglobulin Trials in Sepsis?
AB  - OBJECTIVES: Light chains kappa and lambda are immunoglobulin constituents but
      also circulate independently in blood as free light chains. We investigated
      whether a concomitant abnormality in free light chain and immunoglobulin levels
      could identify a high risk of death sepsis subpopulation to inform future IV
      immunoglobulin trials. We tested whether light chain allelic inclusion occurs in
      circulating B cells. DESIGN: Prospective cohort study. SETTING: Adult general
      ICUs. PATIENTS: Adult sepsis patients without any documented immune comorbidity.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum total free light chain,
      immunoglobulin G, immunoglobulin A, and immunoglobulin M were measured on ICU
      days 1, 3, and 7. Population normal ranges defined normal and abnormal
      categories. Logistic regression models tested any independent relationship
      between high free light chain, immunoglobulins and hospital mortality. CD19 B
      cell subsets expressing cell surface kappa and lambda were quantified by flow
      cytometry; their frequencies were compared against healthy subjects and
      correlation assessed against free light chain concentrations. On ICU day 1, high
      free light chain lambda and high free light chain kappa were seen in 46.5% and
      75.3% of the study cohort (n = 101). Low immunoglobulin levels were commonplace
      (45.5%) at ICU admission. ICU admission day free light chain and immunoglobulin
      concentrations were significantly correlated. Septic patients had significantly
      more CD19 B cells expressing both kappa and lambda compared with healthy controls
      (median [interquartile range] 4.1% [2.4-11.0] vs 1.3% [1.2-2.9], respectively; p
      = 0.0001); these correlated with free light chain concentrations. CONCLUSIONS: To
      our knowledge, abnormalities and associations of free light chain in critically
      ill adults with sepsis have not been previously reported. The additional
      prognostic value of free light chain lambda and the significance of allelic
      inclusion in B cells in sepsis require further investigation.

PMID- 28742551
TI  - Just Because I Am Teaching Doesn't Mean They Are Learning: Improving Our Teaching
      for a New Generation of Learners.

PMID- 28742552
TI  - More on the Causes of Errors in Clinical Reasoning.

PMID- 28742553
TI  - More on the Causes of Errors in Clinical Reasoning.

PMID- 28742555
TI  - Perspectives on the Single GME Accreditation System.

PMID- 28742554
TI  - In Reply to Croskerry and to Patel and Bergl.

PMID- 28742556
TI  - Perspectives on the Single GME Accreditation System.

PMID- 28742557
TI  - In Reply to Buser and to Shannon.

PMID- 28742558
TI  - Gender Equality in Academic Medicine Requires Changes for Both Men and Women.

PMID- 28742559
TI  - Earlier Introduction to the Wards: Are the Medical Students or the Educators Too
      Green?

PMID- 28742560
TI  - Married to Medical School? How to Maintain Relationships as a Medical Student.

PMID- 28742561
TI  - Students: More Than Receivers of Education or Subjects of Medical Education
      Research.

PMID- 28742562
TI  - On Overcoming Imposter Syndrome.

PMID- 28742563
TI  - Identity Capital and Identifying Learners at Risk for Marginalization.

PMID- 28742564
TI  - The Socioeconomic Diversity Gap in Medical Education.

PMID- 28742566
TI  - A Culture of Supremacy in Medicine.

PMID- 28742565
TI  - Ramifications of Recruiting Medical Students From Lower Socioeconomic
      Backgrounds.

PMID- 28742567
TI  - The Barriers to Medical School for DACA Students Continue.

PMID- 28742568
TI  - A Call for Critical Race Theory in Medical Education.

PMID- 28742569
TI  - The Need for Anti-Racism Training in Medical School Curricula.

PMID- 28742570
TI  - An Argument for Flexible Specialty Board Exam Dates: Reducing Gender Disparity
      and Improving Learner Wellness.

PMID- 28742571
TI  - Stupid Consult.

PMID- 28742573
TI  - The Golden Years.

PMID- 28742572
TI  - Artist's Statement: In the Face of Hunger.

PMID- 28742574
TI  - Commentary on "The Golden Years".

PMID- 28742575
TI  - The Need for Developing a Cultural Understanding With Underserved Minority
      Patients in Medicine.

PMID- 28742576
TI  - Whispers.

PMID- 28742578
TI  - Foreword.

PMID- 28742579
TI  - A Review of the Epigenetic Contributions to Endometriosis.
AB  - Epigenetic influences have been postulated to affect the course of endometriosis.
      DNA methyltransferases, estrogen and progesterone receptors, micro-RNAs, and
      histone deacetylators, have shown differential expression in endometriosis
      compared with normal endometrium. Others such as aromatase, Steroid Factor-1, COX
      2, and Homeobox A10 also have epigenetic modifications in endometriosis.
      Limitations in this area of research include heterogeneity in study design,
      patient populations, and methods of analysis. Larger, controlled studies are
      needed. Future targeted uses of this work may include using methylomes to
      noninvasively diagnose endometriosis, or targeting histone-deacetylase inhibitors
      for treatment.

PMID- 28742580
TI  - Surgery and Endometriosis.
AB  - Care of the endometriosis patient today can be complex and difficult. Once
      medical management has been exhausted and symptoms persist patients desire
      further treatment options. This chapter takes an evidence-based approach at
      discussion of patient surgcical options for treatment of endometriosis symptoms.
      Surgical techniques, success rates, patient satisfaction, and risks must be
      discussed and understood at depth before planning patient surgical intervention.
      This chapter provides reference to current surgical management options and
      symptom relief following those interventions.

PMID- 28742581
TI  - Fertility and Endometriosis.
AB  - Approximately 30% to 50% of women that have the diagnosis of endometriosis also
      struggle with infertility. Twenty five percent to 50% of women diagnosed with
      infertility also have endometriosis, but the endometriosis may not be severe
      enough to be the primary etiology of infertility. White women have been reported
      to be more likely than African American women to have endometriosis. In addition,
      risk factors for endometriosis include below average body mass index, smoking,
      and alcohol use. Below is a discussion regarding the various ways in which
      endometriosis decreases fecundity and also discusses potential outcomes of
      fertility treatments regarding endometriosis.

PMID- 28742582
TI  - Endometriosis and Imaging.
AB  - Endometriosis is a condition with variable location, size, and lesion composition
      which poses a diagnostic imaging challenge for the practicing gynecologist.
      Transvaginal ultrasound and magnetic resonance imaging are the most frequent
      imaging techniques used for its evaluation, but transvaginal ultrasound should be
      the first-line approach, as it is often sufficient, followed by modified
      ultrasound techniques. Magnetic resonance imaging should be considered when a
      diagnosis has not been achieved by sonographic means or when the renal system
      needs to be concurrently evaluated. Computed tomography has no role in the
      routine evaluation of endometriosis except in very few particular scenarios.

PMID- 28742583
TI  - Endometriosis and Fertility Preservation.
AB  - Endometriosis is common, affecting 5% to 10% of reproductive age women. Nearly
      half of women with surgical evidence of endometriosis fail to achieve spontaneous
      pregnancy. Surgical treatment of endometriosis can be detrimental to ovarian
      reserve. In the absence of surgical intervention, ovarian reserve may still be
      negatively impacted over time. Fertility preservation was developed for women
      requiring gonadotoxic treatments. Improved methods have led to greater
      consideration of offering these services to women with other disease processes
      that threaten ovarian reserve. This chapter will present the debate regarding use
      of fertility preservation in management of endometriosis, and outline the need
      for further studies.

PMID- 28742584
TI  - Management of Chronic Pelvic Pain.
AB  - The management of chronic pelvic pain poses a significant challenge to both
      physicians and patients. Patients should be evaluated for both gynecologic and
      nongynecologic conditions, and >1 source may be identified. Treatment involves
      medical as well as surgical options, and it is important to set realistic goals
      with patients. Treatment may not be curative, but should improve the patient's
      quality of life.

PMID- 28742585
TI  - Genetics of Endometriosis.
AB  - Endometriosis is a complex, puzzling disease in women of reproductive age. The
      exact cause of the disease is unknown; however, different genetic and
      environmental factors contribute to the evolution of the disorder. Further
      investigation has led to the discovery of inheritance as a complex genetic trait.
      Candidate genes were identified to isolate regions of genes that affect disease
      risk. Additional linkage studies have been performed to map specific genes along
      the entire genome. Recent advances to determine the genetic component of
      endometriosis include genome-wide association studies. This chapter focuses on
      different approaches to identify the genetic links of endometriosis and its
      pathogenesis.

PMID- 28742586
TI  - Summary of Future Developments.
AB  - Endometriosis is a chronic disease with the potential to cause devastating
      clinical manifestations such as infertility and chronic pelvic disease. Current
      treatment is limited to surgical intervention and pharmacologic therapy targeting
      estrogen and progesterone to suppress ectopic endometrial tissue proliferation.
      Undesired side effects and contraindications to the use of hormonal medications
      may reduce treatment options. As the pathogenesis of endometriosis continues to
      be investigated, new therapies will emerge. The identification of genes involved
      in the development of endometriosis may allow targeted therapy to prevent or cure
      disease. In addition, increasing knowledge of the inflammatory pathways that
      promote ectopic endometrial growth will permit the development of pharmacologic
      agents to manipulate these signaling pathways. Utilization of selective
      progesterone receptor modulators, aromatase inhibitors, and modern gonadotropin
      releasing hormone antagonists provide more options to manage disease when
      traditional treatment fails. Individualized therapeutic strategies will soon be a
      reality as a greater understanding of endometriosis is obtained through the
      investigation of genomic studies, molecular pathways, and environmental
      influences.

PMID- 28742588
TI  - Foreword.

PMID- 28742589
TI  - Quality and Safety of Obstetric Practices Using New Modalities- Ultrasound, MR,
      and CT.
AB  - Quality assurance (QA) and safety are important components of obstetric imaging.
      Quality involves accreditation of the imaging unit as well as equipment
      inspection for function and image quality. The personnel working in the unit must
      demonstrate qualifications to perform, evaluate, and interpret the studies.
      Standardizing the required elements of the examination helps assure that a
      quality examination has been performed. QA and safety as well as physician
      requirements and equipment QA programs in ultrasound, computed tomography, and
      magnetic resonance will be discussed with an in depth look at ultrasound due to
      its more frequent use in pregnancy.

PMID- 28742590
TI  - Failed Intrauterine Pregnancy: What Is a Failed Pregnancy, What Is Not?
AB  - Pregnancy failure is defined as a lack of sonographic evidence of current or
      expected viability. Technologic advances in ultrasound imaging continue to
      redefine diagnostic criteria of pregnancy failure or success. When evaluating a
      pregnancy, the first step is an assessment of maternal risk factors for failure.
      Imaging clues such as an empty gestational sac measuring >=25 mm or an embryo >=7
      mm without cardiac activity are reliable signs of pregnancy failure, whereas
      embryonic growth <1 mm/d is not. Combinations of sonographic findings can be used
      for a more accurate prediction of pregnancy success or failure.

PMID- 28742591
TI  - Sonographic Tips for Evaluation of Adnexal Masses in Pregnancy.
AB  - Pregnancy is frequently a women's first contact with the health care system and
      often her first pelvic ultrasound examination. This first sonogram can reveal
      previously unknown adnexal pathology. Approximately 4% of pregnant women will
      have an adnexal mass detected by sonography and 1% to 2% of these masses will
      persist. It is estimated that up to 7% of these persistent masses will be
      malignant. Sonography plays an important role in differentiating benign from
      malignant adnexal masses and physiological from pathologic masses and should be
      used judiciously to complement evaluation and help guide treatment.

PMID- 28742592
TI  - Pregnancy in an Abnormal Location.
AB  - Cesarean scar pregnancy and cervical pregnancy are 2 relatively rare types of
      abnormally implanted pregnancies. Both if unrecognized can result in significant
      morbidity to the patient. The most important issue regarding cesarean scar
      pregnancy and cervical pregnancy is to establish the diagnosis early in order for
      the patient to be adequately counseled and appropriate management carried out.
      For both of these conditions early detection and treatment can result in
      preservation of fertility.

PMID- 28742593
TI  - Prenatal Diagnosis and Evaluation of Abnormal Placentation.
AB  - Abnormalities in placental location or adherence can have important consequences
      on pregnancy outcome for both mother and fetus. Accurate antenatal detection is
      crucial for delivery timing and planning to help reduce perinatal risks for
      adverse events. We review the relevant literature and present a practical
      approach for the prenatal detection of abnormal placentation.

PMID- 28742594
TI  - Cervical Evaluation in Pregnancy: Proper Measurement, Evaluation, and Management.
AB  - Preterm birth is the leading cause of perinatal morbidity and mortality in
      developed nations. The heterogeneous causes of spontaneous preterm birth make
      prediction and prevention difficult. The primary importance of transvaginal
      cervical sonography and cervicovaginal fetal fibronectin lies in their high
      negative predictive values in assessing risk for preterm birth. Cervical length
      may be useful in identifying women who are candidates for cervical cerclage or
      progesterone therapy for preterm birth prevention. Together, cervical length and
      fibronectin can be used in the triaging of women symptomatic for preterm labor.

PMID- 28742595
TI  - Fetal Anatomic Imaging Between 11 and 14 Weeks Gestation.
AB  - Fetal imaging between 11 and 14 weeks is a standard component of prenatal risk
      assessment for aneuploidy. Evaluating the fetus during this gestational age
      window provides the opportunity to reliably examine anatomic structures. Using a
      defined imaging protocol, approximately 50% of major abnormalities can be
      detected. Some abnormalities should almost always be detected, some may be
      detected on occasion and others are not currently detectable. Imagers must be
      familiar with embryologic patterns of development and natural history of
      anomalies. Patients must be informed of the limitations of early anatomic
      evaluation. Currently, early anatomic evaluation does not replace the standard
      second trimester evaluation.

PMID- 28742596
TI  - Advances in Fetal Cardiac Imaging.
AB  - This review presents a detailed discussion on recent trends in fetal cardiac
      imaging. Ultrasound technique which are most useful for clinical practice today
      and will likely change the approach to cardiac evaluation in the future are
      presented.

PMID- 28742597
TI  - Contemporary Modalities to Image the Fetal Brain.
AB  - Fetal brain ultrasound remains as the mainstay for screening fetal intracranial
      anatomy. One of its main advantages is the availability of 3 dimensional and
      other ultrasound modalities for a better understanding of fetal neurodevelopment.
      Neurosonography is performed when findings, suggestive of an abnormality, are
      present on a screening ultrasound or if a high-risk situation of brain injury is
      present. This technique offers the use of complementary imaging planes, axial,
      coronal and sagittal, and the ability to image intracranial anatomy from the
      transabdominal and transvaginal approaches. Fetal brain magnetic resonance
      imaging is more sensitive than ultrasound. As an adjunctive imaging modality,
      magnetic resonance imaging offers additional sequences to complete the
      information on neurodevelopment from different perspectives, such as brain
      metabolism, microstructure, and connectivity.

PMID- 28742598
TI  - Arterial and Venous Doppler in Evaluation of the "At-Risk" Fetus.
AB  - Our practice utilizes Doppler ultrasound as one of the most objective and
      effective methods to assess at-risk pregnancies. This review will discuss the
      application of arterial and venous Doppler techniques in assessing and managing
      various diseases and conditions for high-risk fetuses.

PMID- 28742600
TI  - Cholesterol reduction and macrophage function: role of paraoxonases.
AB  - PURPOSE OF REVIEW: Unregulated uptake of oxidized LDL by macrophages to form foam
      cells is the hallmark for atherosclerosis. The paraoxonase (PON) family of
      enzymes plays a critical role in attenuating atherosclerotic lesion formation by
      hydrolyzing lipid peroxides (LOOHs) and preventing the oxidation of LDL particles
      and by enhancing HDL-mediated cholesterol efflux. Findings in recent years
      suggest novel mechanisms by which PON isoforms interact with macrophages to
      regulate cholesterol metabolism and cellular function. RECENT FINDINGS: The
      association of PON with HDL particles facilitates binding of the particle to
      macrophages and ABCA1-dependent cholesterol efflux. The hydrolysis of membrane
      phospholipids by PON generates lysophosphatidylcholine which is shown to regulate
      expression of cholesterol transport proteins. The PON family also regulates
      multiple aspects of macrophage function. PON attenuates inflammation and prevents
      induction of apoptosis via activation of a scavenger receptor class B type-1
      dependent signaling mechanism. PON limits macrophage-dependent oxidant formation
      by preventing the activation of the membrane-associated NADPH oxidase and by
      stabilizing mitochondria. PON also promotes the differentiation of macrophages to
      an anti-inflammatory phenotype. This function appears to be independent of PON
      enzymatic activity and, rather, is dependent on the ability of endogenous
      sulfhydryls to neutralize pro-inflammatory peroxides. SUMMARY: In recent years,
      the therapeutic efficacy of HDL-based therapies has been subject to dispute.
      Pharmacological approaches that target an increase in the expression and/or
      activity of PON may facilitate macrophage cholesterol metabolism and attenuate
      inflammatory injury.

PMID- 28742602
TI  - Is There a Relationship Between the Functional Movement Screen, Star Excursion
      Balance Test, and Balance Error Scoring System?
AB  - OBJECTIVE: To evaluate associations between the Functional Movement Screen (FMS),
      Star Excursion Balance Test (SEBT), and Balance Error Scoring System (BESS)
      scores. DESIGN: Correlational. SETTING: College athletic training facilities.
      PARTICIPANTS: Fifty-two intercollegiate athletes (men = 36 and women = 16)
      representing 8 sports and cleared for unrestricted sport participation.
      INTERVENTIONS: Participants completed the FMS, SEBT, and BESS, in random order,
      during 1 testing session. Testing order was randomized to control for fatigue and
      learning effects. MAIN OUTCOME MEASURES: Composite and item scores for the FMS,
      SEBT, and BESS. RESULTS: A fair, negative correlation was found between FMS
      asymmetry and SEBT composite (r = -0.31, P = 0.03) scores. Fair, positive
      correlations were reported for FMS rotary stability task and SEBT anterior (r =
      0.37-0.41, P <= 0.007) and posteromedial (r = 0.31, P = 0.03) reaches. Fair,
      negative correlations were reported for FMS deep squat and BESS single-leg firm
      (r = -0.33, P = 0.02), double-leg foam (r = -0.34, P = 0.02) and tandem foam (r =
      -0.40, P = 0.003), FMS inline lunge and BESS single-leg firm (r = -0.39, P =
      0.004), FMS trunk stability pushup and tandem foam (r = -0.31, P = 0.025), and
      FMS composite and BESS single-leg firm (r = -0.37, P = 0.007). Little-to-no
      correlations were reported for remaining comparisons. CONCLUSIONS: Results
      indicate that each instrument provides distinct information about function, with
      only small areas of overlap. Associations between the FMS asymmetry score and
      SEBT composite score may indicate a relationship between movement asymmetry and
      postural stability. Associations between the FMS deep squat and BESS foam tasks
      may be related to underlying neuromuscular control factors.

PMID- 28742603
TI  - Strengths, Limitations, and Geographical Discrepancies in the Eligibility
      Criteria for Sport Participation in Young Patients With Congenital Heart Disease.
AB  - OBJECTIVE: Benefits of physical activity has been shown in children with
      congenital heart disease (CHD). In several forms of CHD, the risk of sudden death
      remains a major concern both for parents and clinicians, who in turn will have to
      consider the risk-benefit ratio of sport participation versus restriction. DATA
      SOURCE: A literature search was performed within the National Library of Medicine
      using the keywords: Sport, CHD, and Eligibility. The search was further refined
      by adding the keywords: Children, Adult, and Criteria. MAIN RESULTS: Fifteen
      published studies evaluating sport eligibility criteria in CHD were included.
      Seven documents from various scientific societies have been published in the past
      decade but which of them should be adopted remains unclear. Our research
      highlighted accuracy and consistency of the latest documents; however,
      differences have emerged between the US and European recommendations. Eligibility
      criteria were consistent between countries for simple congenital heart defects,
      whereas there are discrepancies for borderline conditions including moderate
      valvular lesions and mild or moderate residual defects after CHD repair.
      Furthermore, some of the more severe defects were not evaluated. Multiple
      recommendations have been made for the same CHD, and cut-off values used to
      define disease severity have varied. Published eligibility criteria have mainly
      focused on competitive sports. Little attention was paid to recreational
      activities, and the psychosocial consequences of activity restriction were seldom
      evaluated. CONCLUSIONS: Comprehensive consensus recommendations for sport
      eligibility evaluating all CHD types and stages of repair are needed. These
      should include competitive and recreational activities, use standardized
      classifications to grade disease severity, and address the consequences of
      restriction.

PMID- 28742604
TI  - Disparities in Athletic Trainer Staffing in Secondary School Sport: Implications
      for Concussion Identification.
AB  - OBJECTIVE: First, to assess whether teams at schools with an athletic trainer
      (AT) on staff had a higher number of diagnosed concussions than teams without
      medical personnel present. Second, to assess whether the variability in
      employment of a certified AT by Washington state high schools is patterned by
      socioeconomic and demographic characteristics. DESIGN: Cross-sectional survey.
      SETTING: Washington state public high schools. PARTICIPANTS: Stratified random
      sample of football and soccer coaches (n = 270 teams, 144 schools). INDEPENDENT
      VARIABLES: Presence of an AT and school characteristics (percentage of students
      qualifying for free or reduced price lunch, rural location, enrollment). RESULTS:
      Football and boys' soccer teams at schools with an AT had a significantly greater
      number of athletes with diagnosed concussions compared to teams at schools
      without an AT (P < 0.05). There was no difference in number of athletes with
      diagnosed concussions by AT staffing for girls' soccer. Schools with an AT on
      staff were significantly more likely than schools without an AT to be in an urban
      location (P < 0.001), to have an enrollment of 1000 students or more (P < 0.001),
      and to have a smaller proportion of students eligible for school lunch (P =
      0.005). CONCLUSIONS: The present study provides empirical support for the benefit
      of ATs in diagnosing concussions in high school sport and underscores the
      challenges to AT staffing in lower resource settings. These findings cause us to
      critically reflect on the threshold for medical oversight in contact and
      collision sport from the perspective of risk prevention, and the extent to which
      disparities in this medical oversight are acceptable in the public school
      setting. CLINICAL RELEVANCE: Strategies for increasing AT staffing in high school
      sports settings should be explored given their demonstrated benefit in diagnosing
      concussions.

PMID- 28742605
TI  - Predictors of the Biomechanical Effects of Customized Foot Orthoses in Adults
      With Flat-Arched Feet.
AB  - OBJECTIVE: To determine the potential presence and characteristics of
      biomechanical responders to customized foot orthoses during walking in adults
      with flat-arched feet. DESIGN: Experimental, repeated-measures. SETTING:
      University clinic and laboratory. PARTICIPANTS: Eighteen symptom-free adults with
      flat-arched feet. INTERVENTIONS: Customized foot orthoses. MAIN OUTCOME MEASURES:
      In-shoe foot biomechanics were measured during walking with and without
      customized foot orthoses using 3D analysis. Selected kinematic and kinetic
      variables during baseline walking were compared between subgroups who displayed
      reductions in calcaneal eversion with foot orthoses to those with no change or
      increases. RESULTS: Biomechanical responders displayed significantly greater peak
      calcaneal eversion (+2.2 degrees, P = 0.009). Time to peak calcaneal eversion (
      11%, P = 0.006), peak dorsiflexion of the hallux (-6 degrees, P = 0.001), and
      medial-lateral excursion of the center of pressure during loading response were
      all reduced in the responder subgroup (-2 mm, P <= 0.001). Variables
      significantly different between subgroups were moderately associated with the
      response to foot orthoses (canonical correlation = 0.687, effect size = 0.47, P =
      0.063). CONCLUSIONS: Individuals with increased dynamic foot pronation were more
      likely to show a favorable biomechanical response to customized foot orthoses,
      providing preliminary evidence to support the stratified use of foot orthoses to
      optimize their effectiveness.

PMID- 28742606
TI  - Functional Movement Screening and Injury Rates in High School and Collegiate
      Runners: A Retrospective Analysis of 3 Prospective Observational Studies.
AB  - OBJECTIVE: Determine if the Functional Movement Screening (FMS) can be used to
      predict injury in high school and collegiate cross-country and track runners.
      DESIGN: Prospective Observational, Cohort Study, Level of Evidence, 2. SETTING:
      High schools and colleges in the Central Ohio area. PATIENTS: Inclusion: (1)
      cross-country or track runners at participating schools; (2) full participation
      without restrictions; and (3) signed informed assent or consent. Exclusion: (1)
      Any injury or lower extremity surgery within 30 days; (2) planned limited
      participation in the upcoming season; or (3) other participation restrictions.
      INTERVENTIONS: Functional Movement Screening was completed before the start of
      each season. Injuries were tracked during the regular season. No interventions
      were made based on FMS score. MAIN OUTCOME MEASURES: Functional Movement
      Screening scores, including overall, lower extremity, and specific exercises were
      compared between runners who did and did not sustain an injury using 2 sample t
      tests. A cutoff FMS score of <=14 (most common in previous studies), and <=15
      (determined by a receiver operating characteristic curve), were compared using
      chi tests. RESULTS: One hundred eighty-three runners were enrolled in the study.
      Overall, 32 (17.5%) runners sustained an injury. Functional Movement Screening
      score was not accurate in predicting injury for <=14 (sensitivity: 65.6%;
      specificity: 39.7%; and area under the curve = 0.501) or <=15 (sensitivity: 84.4%
      and specificity: 23.8%). There was no difference in risk of injury for runners
      with a FMS score of <=14 (15.5%) and >14 (18.8%) (P = 0.572) or with a FMS score
      of <=15 (17.5%) and >15 (17.4%) (P = 0.988). CONCLUSIONS: Functional Movement
      Screening composite score may not be useful for injury prediction in populations
      of high school and collegiate runners.

PMID- 28742607
TI  - Pitch Counts in Youth Baseball and Softball: A Historical Review.
AB  - OBJECTIVE: Pitching injuries are getting increased attention in the mass media.
      Many references are made to pitch counts and the role they play in injury
      prevention. The original purpose of regulating the pitch count in youth baseball
      was to reduce injury and fatigue to pitchers. This article reviews the history
      and development of the pitch count limit in baseball, the effect it has had on
      injury, and the evidence regarding injury rates on softball windmill pitching.
      DATA SOURCE: Literature search through PubMed, mass media, and organizational Web
      sites through June 2015. RESULTS: Pitch count limits and rest recommendations
      were introduced in 1996 after a survey of 28 orthopedic surgeons and baseball
      coaches showed injuries to baseball pitchers' arms were believed to be from the
      number of pitches thrown. Follow-up research led to revised recommendations with
      more detailed guidelines in 2006. Since that time, data show a relationship
      between innings pitched and upper extremity injury, but pitch type has not
      clearly been shown to affect injury rates. Current surveys of coaches and players
      show that coaches, parents, and athletes often do not adhere to these guidelines.
      There are no pitch count guidelines currently available in softball. CONCLUSIONS:
      The increase in participation in youth baseball and softball with an emphasis on
      early sport specialization in youth sports activities suggests that there will
      continue to be a rise in injury rates to young throwers. The published pitch
      counts are likely to positively affect injury rates but must be adhered to by
      athletes, coaches, and parents.

PMID- 28742608
TI  - Epidemiology of Injuries in Women's Lacrosse: Implications for Sport-, Level-,
      and Sex-Specific Injury Prevention Strategies.
AB  - OBJECTIVE: By the end of 2013, the United States had an estimated 278 000 female
      lacrosse players, with half of those participating at the youth level. The
      effects of the sport's rapid growth on injury rates have yet to be determined.
      The purpose of this clinical review is to synthesize the available published data
      on injuries that have occurred in the sport of women's lacrosse. Of particular
      interest was the risk of injury based on the level of play and position. DATA
      SOURCES: A comprehensive literature search was performed in PubMed, High Wire
      Press, SPORTDiscus, Google Scholar, and Ovid using the keywords "Lacrosse
      Injuries," "Epidemiology Lacrosse Injuries," "Lacrosse Injury," "Lacrosse," and
      "Injury." STUDY SELECTION: The electronic search included material published
      during or after 1950. In addition, all bibliographies of electronically found
      sources were cross-referenced to identify any additional publications that were
      not produced in the electronic searches. DATA EXTRACTION: All articles with data
      on women's injury rates were categorized by overall injury rates, rates by
      session (competition vs practice), nature of injury, location, type, severity,
      and player position. DATA SYNTHESIS: Injury rates increase with age: from youth
      leagues to high school and finally to the collegiate level. Rates of injury
      varied from 0.03 to 3.9 injuries/100 athletes. Women's game injury rates are
      consistently higher than practice injury rates (ranging from 0.2 to 7.1 vs 0.01
      to 3.3). Injuries occur most frequently from stick-to-player or player-to-ball
      contact, rather than player-to-player contact. Women sustain a higher percentage
      of head and facial injuries relative to male lacrosse players. The most common
      types of injuries for women are concussions, sprains, contusions, and
      lacerations. More than half of all injuries are in the mild category resulting in
      players missing practice and games for 1 to 7 days. Offensive players had the
      most injuries, followed by defensive players and then midfielders, with goalies
      having the fewest number of injuries. CONCLUSIONS: In women's lacrosse, the rules
      and equipment used are substantially different than for the men's game. Face and
      hand injuries are more prevalent for women when compared with men, and ankle
      injuries are most prevalent in female youth. Medical professionals who treat
      lacrosse players can benefit from an improved understanding of the types and
      rates of the injuries they are likely to encounter. Improved awareness of
      lacrosse-specific injuries can assist these professionals to be more prepared to
      treat these athletes, which may lead to improved care and outcomes.

PMID- 28742609
TI  - The Efficacy of Dynamic Contract-Relax Stretching on Delayed-Onset Muscle
      Soreness Among Healthy Individuals: A Randomized Clinical Trial.
AB  - OBJECTIVE: To evaluate the efficacy of dynamic contract-relax stretching on
      delayed-onset muscle soreness (DOMS) in the calf muscle of healthy individuals.
      DESIGN: Randomized clinical trial. SETTING: Research laboratory. PARTICIPANTS:
      Three groups of 16 healthy participants (n = 48) were recruited by convenience
      sampling. INTERVENTIONS: Three sets of resisted bilateral heel-raising exercises
      until exhaustion were conducted to initiate DOMS. Participants were randomly
      allocated into control group without any interventions, dynamic contract-relax
      stretching (DS), or static stretching (SS) groups. Dynamic contract-relax
      stretching and SS groups performed DS and SS, respectively, on the dominant leg
      twice a day for 5 consecutive days (before time points of outcome measurements at
      24, 48, 72, 96, and 120 hours postexercise, respectively). MAIN OUTCOME MEASURES:
      Muscle soreness, lower leg girth, pressure pain threshold (PPT), range of motion
      (ROM), and muscle strength were measured before exercise, immediately after, and
      at 24, 48, 72, 96, and 120 hours postexercise. RESULTS: There was a significant
      effect of time in all outcome measures including muscle soreness, lower leg
      girth, PPT, ROM, and muscle strength; however, there were no significant group
      differences or group by time interactions. CONCLUSIONS: The effect of DS on
      relieving DOMS in the calf muscle is insignificant in this study. Further
      evidence is needed to prove the efficacy of DS on DOMS. CLINICAL RELEVANCE:
      Stretching is commonly recommended before and after exercise; however, this study
      showed no significant impact of DS or SS in treating DOMS.

PMID- 28742610
TI  - Near Point of Convergence and Gait Deficits in Adolescents After Sport-Related
      Concussion.
AB  - OBJECTIVE: To prospectively examine gait characteristics of participants acutely
      after concussion with and without receded near point of convergence (NPC),
      compared with healthy controls. DESIGN: Cross-sectional study. SETTING: Sports
      medicine clinic. PARTICIPANTS: Patients examined after concussion (n = 33; mean
      +/- SD = 7.2 +/- 3.1 days) and a group of uninjured athletes (n = 31) completed a
      Postconcussion Symptom Scale, underwent NPC testing, and single/dual-task gait
      assessments. INDEPENDENT VARIABLES: Near point of convergence was defined as the
      patient-reported diplopia distance when a fixation target moved toward the nose.
      Receded NPC was defined as a distance >5 cm from the tip of the nose. MAIN
      OUTCOME MEASURES: Spatiotemporal gait characteristics in single-task and dual
      task conditions were evaluated with analysis of variance; correlations were
      calculated between NPC and gait measures. RESULTS: Eighteen of 33 (55%) patients
      with concussion presented with receded NPC. Those with receded NPC exhibited
      slower gait speed (single-task = 1.06 +/- 0.14 m/s vs 1.19 +/- 0.15 m/s; dual
      task = 0.80 +/- 0.13 m/s vs 0.94 +/- 0.13 m/s; P = 0.003) and shorter stride
      lengths (single-task = 1.11 +/- 0.10 m vs 1.24 +/- 0.11 m; dual-task = 0.97 +/-
      0.11 m vs 1.09 +/- 0.11 m; P = 0.001) than healthy controls. Near point of
      convergence was moderately correlated with dual-task average walking speed for
      the normal NPC group (rho = -0.56; P = 0.05). Postconcussion Symptom Scale scores
      did not significantly differ between groups (27 +/- 18 vs 28 +/- 16).
      CONCLUSIONS: After concussion, adolescents with receded NPC exhibited significant
      gait-related deficits compared with healthy controls, whereas those with normal
      NPC did not. Vergence and gross motor system dysfunction may be associated after
      concussion. Gait and vergence measures may contribute useful information to
      postconcussion evaluations.

PMID- 28742611
TI  - A Rare Presentation of a Morel-Lavallee Lesion of the Lower Leg Successfully
      Treated With Ultrasound-Guided Aspiration.
AB  - A Morel-Lavallee lesion (MLL) is a relatively rare condition that is caused by a
      traumatic shearing force. This force leads to a closed degloving injury of the
      subcutaneous tissue and fascia that creates a potential space that can fill with
      lymph, blood, and necrotic fat. The MLLs are traditionally seen after high impact
      trauma and typically located at the greater trochanter and pelvis, although
      recent reports have found them to be located at the knee, thigh, and lower leg.
      The MLLs typically present as swelling at the site of injury, which can be
      difficult to differentiate from several other diagnoses. This case report
      discusses an MLL in the lower extremity that occurred during a rugby game. A lack
      of familiarity with MLLs often leads to delayed diagnosis and treatment. The
      diagnosis was eventually made with an magnetic resonance imaging, and the lesion
      was successfully treated with ultrasound-guided aspiration and compression. The
      athlete was able to return to play without recurrence of the lesion.

PMID- 28742612
TI  - Short Sleep and Adolescents' Performance on a Concussion Assessment Battery: An
      Experimental Sleep Manipulation Study.
AB  - OBJECTIVE: Correlational studies have linked short sleep to adolescents' report
      of postconcussion symptoms and cognitive performance during concussion
      assessments. This study tested whether those are cause-effect relationships.
      DESIGN: Three-week randomly counterbalanced, within-subjects, crossover
      experiment. SETTING: Adolescents slept at home with weekly visits to an
      outpatient clinic for sleep monitor uploads and outcome assessments.
      PARTICIPANTS: Twenty-four healthy 14- to 17.9-year-olds. CONDITIONS: After an
      initial sleep-stabilization period, adolescents experienced 5-night spans of
      short sleep (SS; 6.5 hours/night in bed) versus Healthy Sleep Opportunity (HS;
      9.5 hours/night in bed). MAIN OUTCOME MEASURES: Cognitive indexes and the
      postconcussion symptom scale (PCSS) from the Immediate PostConcussion Assessment
      and Cognitive Testing. RESULTS: Adolescents reported significantly worse symptoms
      on the PCSS after SS than HS, even after excluding items manifestly related to
      sleep. Verbal memory was also worse after SS than HS, though the effect was
      small. The manipulation did not significantly affect other cognitive indexes.
      CONCLUSIONS: A realistic "dose" of short sleep, similar to what many adolescents
      experience regularly on school nights, can cause or contribute to symptom reports
      during concussion assessments. Consistent with previous sleep research, one-on
      one cognitive tests seem to be less sensitive than measures of emotional and
      behavioral functioning to the effects of short sleep.

PMID- 28742613
TI  - The Influence of Heavier Football Helmet Faceguards on Head Impact Location and
      Severity.
AB  - OBJECTIVE: To determine whether players with heavier faceguards have increased
      odds of sustaining top of the head impacts and head impacts of higher severity.
      DESIGN: Cohort study. SETTING: On-field. PARTICIPANTS: Thirty-five division I
      collegiate football players. INTERVENTIONS: Faceguard mass was measured. Head
      impact location and severity (linear acceleration [gravity], rotational
      acceleration [radian per square second], and Head Impact Technology severity
      profile [unitless]) were captured for 19 379 total head impacts at practices
      using the Head Impact Telemetry System. MAIN OUTCOME MEASURES: Players'
      faceguards were categorized as either heavier (>480 g) or lighter (<=480 g) using
      a median split. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      computed for sustaining top of the head impacts between faceguard groups using a
      random intercepts generalized logit model. We compared head impact severity
      between groups using random intercepts general linear models (alpha = 0.05).
      Player position was included in all models. RESULTS: Overall, the 4 head impact
      locations were equally distributed across faceguard groups (F(3,26) = 2.16, P =
      0.117). Football players with heavier faceguards sustained a higher proportion
      impacts to the top of the head (24.7% vs 17.5%) and had slightly increased odds
      of sustaining top (OR, 1.72; 95% CI, 1.01-2.94) head impacts rather than front of
      the head impacts. CONCLUSIONS: Football players wearing heavier faceguards might
      be slightly more prone to sustaining a higher proportion of top of the head
      impacts, suggesting that greater faceguard mass may make players more likely to
      lower their head before collision. Individuals involved with equipment selection
      should consider the potential influence of faceguard design on head impact
      biomechanics when recommending the use of a heavier faceguard.

PMID- 28742614
TI  - Compression Socks Worn During Flight and Hemostatic Balance in Boston Marathon
      Runners on Oral Contraceptives.
AB  - OBJECTIVE: To investigate the effect of oral contraceptive (OC) use and
      compression socks on hemostatic activation in women flying cross-country to and
      from a marathon. DESIGN: Prospective study. SETTING: 2015 Boston Marathon.
      PARTICIPANTS: Women were divided into non-OC using (CONTROL; n = 12), OC-using
      (OC; n = 15), and OC-using plus compression sock (OC + SOCK; n = 14) groups.
      INTERVENTION: Women in OC + SOCK wore compression socks during flights to and
      from the marathon. MAIN OUTCOME MEASURES: Venous blood samples were collected
      within 24 hours of arriving in Boston (EXPO), immediately after the marathon
      (RUN), and within 24 hours after a return flight home (Post-Flight) for analysis
      of thrombin-antithrombin complex (TAT), d-dimer, and tissue plasminogen activator
      (t-PA). RESULTS: TAT did not increase with exercise (P = 0.48) and was not
      affected by group (P = 0.08) or the interaction between these 2 factors (P =
      0.80). Group, time, and their interaction were significant for d-dimer (all P <
      0.05) such that d-dimer increased with acute exercise to a greater extent (Delta
      d-dimer from expo to postrace = 909.5 +/- 1021.9 ng/mL) in the OC + SOCK group
      relative to OC (Delta d-dimer = 240.0 +/- 178.5 ng/mL; P = 0.02) and CONTROL
      (Delta d-dimer = 230.3 +/- 120.3 ng/mL; P = 0.02). There was a significant effect
      of time, group, and the interaction on t-PA (all P < 0.01) such that t-PA
      increased with acute exercise to a greater extent (Delta t-PA from expo to
      postrace = 19.6 +/- 10.0 ng/mL) in the CONTROL group relative to OC (Delta t-PA =
      4.0 +/- 1.8 ng/mL; P < 0.01) and OC + SOCK (Delta t-PA = 3.3 +/- 1.2 ng/mL; P <
      0.01). CONCLUSIONS: Female runners using OCs did not exhibit disproportionately
      increased coagulation. The use of compression socks in women on OCs,
      surprisingly, resulted in a greater increase in d-dimer after exercise.

PMID- 28742615
TI  - Trunk Side Strain Has a High Incidence in First-Class Cricket Fast Bowlers in
      Australia and England.
AB  - OBJECTIVE: To investigate the past incidence of side strain injury and its
      associated factors in first-class cricket fast bowlers in Australia and England.
      DESIGN: Retrospective case series. SETTING: Professional cricket. PARTICIPANTS:
      Cricket fast bowlers who were professionally contracted full time at first-class
      level in Australia and England in 2011. All bowlers were male and aged 18 or
      older. A bowler was defined as a fast bowler if the wicketkeeper would take their
      stance back from the stumps. There were 207 participants. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The association between bowling arm, player
      height, active trunk lateral flexion range of motion, side bridge endurance,
      volume of first-class cricket played, and the history of injury was determined.
      RESULTS: Over half of the bowlers had sustained at least 1 side strain in their
      career. Seventy-seven percent of primary injuries occurred in bowlers aged 24 or
      under. A higher proportion of injured bowlers had reached first-class volume in
      their career. Recurrence occurred in 30% of bowlers, with over 30% of these
      bowlers sustaining at least 1 further recurrence. Nearly half of all recurrences
      occurred within 2 years with a further quarter in the next year. The injury was
      not associated with any measured factors. CONCLUSIONS: Side strain is a common
      injury among first-class cricket fast bowlers, especially at younger ages. It was
      associated with the volume of first-class cricket played. Recurrence was common
      and occurred most frequently in the first 2 years after primary injury.

PMID- 28742616
TI  - Twenty-Year Systematic Review of the Hip Pathology, Risk Factors, Treatment, and
      Clinical Outcomes in Artistic Athletes-Dancers, Figure Skaters, and Gymnasts.
AB  - OBJECTIVE: To identify (1) the predominant level of evidence of the clinical
      studies regarding the hip pathology, risk factors, treatment, and clinical
      outcomes in artistic athletes (dancers, figure skaters, and gymnasts) (2) the
      most commonly reported hip pathology, risk factors, treatments, and clinical
      outcomes in dancers, figure skaters, and gymnasts. METHODS: To conduct this
      systematic review PubMed, EMBASE, and Scopus databases were searched for relevant
      studies and pertinent data were collected from the eligible articles. Included
      were studies which reported hip injuries in artistic athletes, the risk factors,
      treatment, and/or the clinical outcomes. We excluded case reports or irrelevant
      studies. No meta-analysis was performed because of study heterogeneity. The
      methodical index for nonrandomized studies (MINORS) criteria were used for
      quality control. MAIN RESULTS: Thirty-eight studies were included in the
      analysis. The mean MINORS score was 13.6 +/- 4.6 points indicating fair quality
      of evidence of the included articles. The predominant level of evidence was level
      IV. Chondrolabral pathology and muscle injuries were the most commonly reported
      pathologies. We found only 2 risk factor analysis studies; however, many studies
      reported risk correlation between artistic sports or imaging findings and hip
      pathology. Treatment strategies were reported in only 7 studies, clinical
      outcomes are significantly underreported. CONCLUSION: Chondrolabral pathology was
      the most commonly reported hip pathology in artistic athletes, however,
      prospective cohort studies are necessary to really understand these injuries and
      their associated risk factors. The lack of clinical outcomes is significant and
      future data collection is required to assess the effectiveness of the various
      treatments.

PMID- 28742617
TI  - Simple Single-Pass Technique for Ultrathin Descemet Stripping Automated
      Endothelial Keratoplasty: A Pilot Study.
AB  - PURPOSE: To assess intraoperative and postoperative graft thickness (GT) after
      donor deturgescence for ultrathin Descemet stripping automated endothelial
      keratoplasty and to evaluate visual outcomes, endothelial cell density, and
      patient satisfaction at 1 year. METHODS: Prospective interventional case series
      of patients with Fuchs endothelial dystrophy, Fuchs endothelial dystrophy and
      cataract, and pseudophakic bullous keratopathy (n = 12 grafts). The donor cornea
      was allowed to thin out by simple evaporation on an artificial anterior chamber,
      to the required precut thickness, before a single microkeratome pass. GT after
      microkeratome cut, at 1 week, 1, 3, 6, and 12, months was measured. Early
      Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, Pelli
      Robson contrast sensitivity, endothelial cell density, and score on the visual
      function questionnaire (VFQ-25) were assessed. RESULTS: Mean intraoperative
      postmicrokeratome cut GT was 78.9 +/- 33.3 MUm. Mean GT at 1 week, 1, 3, 6, and
      12 months was 70.7, 70.9, 62.8, 66.5, and 58.9 MUm, respectively. Mean initial
      donor corneal thickness was 647 +/- 67 MUm, and mean precut thickness was 526 +/-
      4.5 MUm (mean thinning time: 17 min). Best-corrected visual acuity at 1 week, 1,
      3, 6, and 12 months was 68.8, 76.9, 76.3, 76.9, and 78.6 letters with 9-letter
      gain at 12 months (P = 0.02). Mean endothelial cell loss at 3, 6, and 12 months
      was 36.8% +/- 6.75%, 37.2% +/- 8%, and 37.9% +/- 9.75% loss, respectively. At 1
      year, 83.3% of patients achieved >=20/40 (6/12) and 66.7% of patients achieved
      >=20/32 (6/9.5). VFQ-25 testing showed an improvement in the visual function.
      CONCLUSIONS: This pilot study demonstrates a simple graft deturgescence technique
      that reproducibly creates ultrathin grafts without donor wastage.

PMID- 28742618
TI  - Changes in Higher-Order Aberrations After Phototherapeutic Keratectomy for
      Subepithelial Corneal Infiltrates After Epidemic Keratoconjunctivitis.
AB  - PURPOSE: To investigate how corneal aberrations change after phototherapeutic
      keratectomy (PTK) for subepithelial infiltrates after adenoviral
      keratoconjunctivitis. METHODS: The records of patients who underwent
      transepithelial PTK for subepithelial infiltrates were retrospectively reviewed.
      Preoperative best-corrected visual acuity (VA) and the results of slit-lamp
      biomicroscopy examinations were recorded. The PTK procedure was performed under
      topical anesthesia with an Amaris excimer laser. Patients' manifest refraction
      values, topographical examination results, and corneal aberrations before and
      after surgery were analyzed. RESULTS: Twenty-four eyes of 16 women (84.3%) and 3
      men (15.7%) were treated. The mean follow-up time was 6.0 +/- 2.5 (range: 3-12)
      months, and the mean ablation depth was 82.3 +/- 1.0 (range: 80-88) MUm.
      Postoperative median best-corrected VA increased from 0.6 (range: 0.4-1.0)
      logarithm of the minimum angle of resolution to 0.2 (range: 0.1-0.5) logarithm of
      the minimum angle of resolution (P = 0.048), coma decreased from 0.56 (range:
      0.29-0.37) to 0.44 (range: 0.07-0.74), secondary astigmatism decreased from 0.45
      (range: 0.12-1.9) to 0.17 (range: 0.03-0.49), and total higher-order aberrations
      decreased from 1.24 (range: 0.61-6.74) to 0.9 (range: 0.33-1.64) (P = 0.008,
      0.0032, and 0.018, respectively). CONCLUSIONS: PTK is an effective method for
      treating corneal opacity after epidemic keratoconjunctivitis, which yields
      significant improvements in both VA and visual quality.

PMID- 28742619
TI  - Use of Topical Insulin to Treat Refractory Neurotrophic Corneal Ulcers.
AB  - PURPOSE: To report the clinical course of 6 patients with refractory neurotrophic
      corneal ulcers that were treated with topical insulin drops. METHODS:
      Retrospective chart review of patients who had neurotrophic corneal ulcers or
      epithelial defects refractory to standard medical and surgical treatment. Insulin
      drops, prepared by mixing regular insulin in artificial tears with a polyethylene
      glycol and propylene glycol base at a concentration of 1 unit per milliliter,
      were prescribed 2 to 3 times daily. RESULTS: Six patients, aged 2 to 73 years,
      developed neurotrophic corneal ulcers refractory to a range of medical and
      surgical treatments, including bandage contact lens, amniotic membrane grafting,
      and permanent tarsorrhaphy. Each patient was administered topical insulin drops
      with complete corneal reepithelialization within 7 to 25 days. CONCLUSIONS:
      Topical insulin may be a simple and effective treatment for refractory
      neurotrophic corneal ulcers. Further study is required to determine the clinical
      efficacy and side effect profile of insulin drops.

PMID- 28742620
TI  - Comparison of 5% Sulfur Hexafluoride Versus 100% Air Tamponade in Descemet
      Membrane Endothelial Keratoplasty.
AB  - PURPOSE: To compare the rebubbling rate and clinical outcomes of Descemet
      membrane endothelial keratoplasty (DMEK) with 5% sulfur hexafluoride (SF6) gas
      versus 100% air as a tamponade for graft attachment. METHODS: Retrospective,
      comparative, interventional case series including 368 consecutive pseudophakic
      eyes with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy that
      underwent DMEK in a tertiary referral center between October 2010 and August 2015
      using either air (group 1, 191 eyes) or 5% SF6 (group 2, 177 eyes) as a
      tamponade. The rebubbling rate, complications, best-corrected distance visual
      acuity (BCVA), manifest refraction, and endothelial cell density were analyzed
      before and at 1 week, 1, 3, 6, 12, 24, and 36 months after surgery. RESULTS: The
      rebubbling rate was 20.4% (39/191, group 1) versus 6.8% (12/177, group 2; P <
      0.001). Complications included cystoid macular edema (n = 5, group 1, and n = 10,
      group 2; P = 0.14) and 1 case of presumed allograft rejection (n = 1, group 2).
      The follow-up period was 12 +/- 8 months for group 1 and 6 +/- 4 months for group
      2. BCVA (logarithm of the minimum angle of resolution) had improved after 12
      months from 1.43 +/- 0.63 to 0.18 +/- 0.26 (group 1, P < 0.001) and from 1.8 +/-
      0.63 to 0.18 +/- 0.17 (group 2, P < 0.001). The percentage of eyes with BCVA
      >=0.2 logarithm of the minimum angle of resolution at 12 months was 70.9%
      (90/127, group 1) and 78.4% (40/51, group 2; P = 0.3). Endothelial cell loss at
      12 months after DMEK was 44 +/- 18% (group 1) versus 33 +/- 15% (group 2, P =
      0.07). CONCLUSIONS: The use of a tamponade with 5% SF6 yielded a significantly
      lower incidence of graft detachment requiring surgical reintervention with no
      detrimental effect on graft endothelial cells. Thus, routine use of 5% SF6 for a
      graft tamponade in DMEK is recommended.

PMID- 28742621
TI  - Long-Term Tomographic Evaluation of Unilateral Keratoconus.
AB  - PURPOSE: To report 5 cases of advanced unilateral keratoconus documented by
      sequential tomographic evaluation. METHODS: Retrospective review over a 10-year
      period at a single practice identifying patients with unilateral keratoconus by
      advanced imaging throughout the follow-up period. RESULTS: Five patients were
      identified with progressive keratoconus in 1 eye and no changes in the fellow eye
      based on full tomographic evaluation and analysis of both anterior and posterior
      corneal surfaces and corneal thickness with a mean follow-up period of 59 months
      (range 39-86). CONCLUSIONS: Keratoconus is believed to be a bilateral disease
      that can present asymmetrically. We present 5 cases that appear to be true
      unilateral keratoconus with no associated mechanical environmental factors.

PMID- 28742622
TI  - Rational therapeutic choice for older patients with lymphoma.
AB  - PURPOSE OF REVIEW: The choice for an optimal treatment in older lymphoma patients
      is a real challenge for hemato-oncologists. They have to treat a potentially
      curative lymphoma, and concomitantly protect their patients from unacceptable
      toxicities. Some recommendations are provided for the major subtypes of lymphomas
      including the antitumoral treatment and primarily the optimal supportive care.
      RECENT FINDINGS: All the recent literature data converge to say that the approach
      of an older patient with a malignant hemopathy is a multistep procedure. This
      process comprises the appraisal of life expectancy of the patient with or without
      the disease, the prognostic factors of the tumor, the functional, physiological
      and cognitive functions evaluation, the socio-economical environment and the
      patient's expectancy in terms of quality of life. Major progresses have been
      achieved in the management of diffuse large B cell lymphoma and mantle cell
      lymphoma in patients up to 80 and above 80 years old. SUMMARY: With all these
      information in hands, the hematologist will decide if the treatment's objective
      is the standard treatment with optimal supportive care (fit patients), tailor
      made adapted chemotherapy (unfit patients) or preservation of quality of life
      (frail patients).

PMID- 28742623
TI  - Prediction of Orthokeratology Lens Decentration with Corneal Elevation.
AB  - SIGNIFICANCE: Lens decentration is common and unavoidable to some extent during
      ortho-k treatment. By using a simplified method, we are able to predict the
      magnitude and direction of ortho-k lens decentration, which provides useful
      insights in screening for ideal ortho-k candidates and to make a quick decision
      when decentration happens. PURPOSE: The aim of this study was to investigate the
      influence of corneal elevation asymmetry on ortho-k lens decentration. METHODS:
      Thirty-six eyes of 36 subjects were fitted with four-curve reverse geometry ortho
      k contact lenses. Corneal topography was collected before and 1 month after ortho
      k lens wear. The difference in corneal elevation at the 8-mm chord of the
      respective two principal meridians of corneal astigmatism was calculated. Vector
      analyses were performed on these differences to calculate the magnitude and
      direction of a vector (corneal asymmetry vector). The relationship between the
      angle and magnitude of corneal asymmetry vector and lens decentration was
      analyzed. RESULTS: Baseline refractive sphere and cylinder for the 36 tested eyes
      were -2.84 +/- 1.04 diopters (D) (range, -4.75 to -1.00 D) and -0.21 +/- 0.28 D
      (range, -1.00 to 0 D), respectively. The mean magnitude of lens decentration was
      0.72 +/- 0.26 mm (0 to 1.34 mm). For overall displacement, inferotemporal
      decentration was the most common as observed in 24 eyes (67%). The mean angle of
      the corneal asymmetry vector (202 +/- 39 degrees) was significantly correlated to
      the mean angle of lens decentration (200 +/- 39 degrees) (r = 0.76, P < .001).
      The magnitude of corneal asymmetry vector significantly contributed to the
      magnitude of lens decentration (standardized beta = 0.448, P = .002) whereas the
      other tested variables did not affect lens decentration (all P > .05).
      CONCLUSIONS: Lens decentration is a common phenomenon in ortho-k that mostly
      happens toward the inferotemporal quadrant of the cornea. The magnitude and
      direction of lens decentration are predetermined by paracentral corneal
      asymmetry.

PMID- 28742624
TI  - Impact of a Mandated Change in Buprenorphine Formulation.
AB  - OBJECTIVE: This study examines the impact of an insurance-mandated change in
      formulation of buprenorphine/naloxone (BNX) for patients with opioid use disorder
      treated in a primary care clinic. METHODS: A retrospective cohort study was
      conducted to determine the proportion of patients who were switched back to the
      previous BNX formulation and rates of aberrant urine drug tests for the 3 months
      before and 3 months after a mandated change in BNX from the sublingual film to
      the rapidly dissolving tablet (BNX-RDT). Aberrant urine drug tests were defined
      as the presence of cocaine, nonprescribed opioids/benzodiazepines, or the absence
      of buprenorphine. RESULTS: In all, 186 patients were included in the analysis. At
      3 months after the change, 36.0% of patients remained on BNX-RDT at equivalent
      dose, 9.1% were prescribed a higher dose of BNX-RDT, 52.7% were switched back to
      their previous formulation after a trial of BNX-RDT, and 2.2% dropped out of
      care. There was no significant change in the rates of aberrant urine drug tests
      pre and postchange (36.6% vs 33.7%; P = 0.27) or in any individual component of
      urine drug testing. Age, sex, and starting dose were not associated with
      remaining on BNX-RDT at equivalent dose, compared with increasing dose or
      changing formulation. CONCLUSIONS: Most patients were dissatisfied with the
      change in formulation and requested a return to the previous formulation. This
      change did not appear to impact drug use; however, the flexibility that permitted
      patients to switch back to their previous BNX formulation likely attenuated the
      policy's impact.

PMID- 28742625
TI  - Online Sales of Unscheduled Pharmaceutical Agents: A Case Report of Tianeptine
      Use in the United States.
AB  - : Tianeptine is a tricyclic antidepressant that stimulates mu-opioid receptors at
      high doses. It is marketed and used across Europe and Latin America as an
      antidepressant, but is not approved by the Food and Drug Administration for use
      in the United States. In the United States, tianeptine is sold through online
      health stores as a cognition enhancer, dietary supplement, or as research
      chemical. We report the case of a 36-year-old man with a history of major
      depressive disorder, responsive to sertraline, who turned to the unmonitored use
      of tianeptine purchased online to treat residual feelings of apathy and boredom.
      His use of tianeptine was marked by rapidly escalating doses and a significant
      withdrawal syndrome that made discontinuation of this substance difficult. This
      case serves as a reminder that unscheduled pharmaceutical agents are available
      for misuse by the general population and have the potential to cause significant
      harm. Therefore, medical providers must be aware of and screen for the use of
      such products amongst their patients.

PMID- 28742627
TI  - Measurement Error of a Simplified Protocol for Quantitative Sensory Tests in
      Chronic Pain Patients.
AB  - BACKGROUND AND OBJECTIVES: Large-scale application of Quantitative Sensory Tests
      (QST) is impaired by lacking standardized testing protocols. One unclear
      methodological aspect is the number of records needed to minimize measurement
      error. Traditionally, measurements are repeated 3 to 5 times, and their mean
      value is considered. When transferring QST to a clinical setting, reducing the
      number of records would be desirable to meet the time constraints encountered in
      a routine clinical environment and to reduce the testing burden to chronic pain
      patients. However, there might be a trade-off between measurement error and
      number of records. We determined the measurement error of a single versus the
      mean of 3 records of pressure pain detection threshold (PPDT), electrical pain
      detection threshold (EPDT), and nociceptive withdrawal reflex threshold (NWRT) in
      429 chronic pain patients recruited in a routine clinical setting. METHODS: We
      calculated intraclass correlation coefficients and performed a Bland-Altman
      analysis. RESULTS: Intraclass correlation coefficients were all clearly greater
      than 0.75, and Bland-Altman analysis showed minute systematic errors with small
      point estimates and narrow 95% confidence intervals. Reducing the number of
      records from traditionally 3 to only 1 did not lead to relevant measurement error
      in PPDT, EPDT, or NWRT. CONCLUSIONS: This study contributes to a standardized QST
      protocol, and based on the minimal measurement error of 1 single record of PPDT,
      EPDT, and NWRT, we submit to reduce the testing burden. This would allow saving
      time, resources, and patient discomfort.

PMID- 28742628
TI  - What you don't know can hurt you: more information and communication are needed
      regarding menopausal therapies.

PMID- 28742629
TI  - Noonan Syndrome: An Underestimated Cause of Severe to Profound Sensorineural
      Hearing Impairment. Which Clues to Suspect the Diagnosis?
AB  - OBJECTIVE: To highlight Noonan syndrome as a clinically recognizable cause of
      severe to profound sensorineural hearing impairment. STUDY DESIGN: New clinical
      cases and review. SETTING: Patients evaluated for etiological diagnosis by a
      medical geneticist in a reference center for hearing impairment. PATIENTS: Five
      patients presenting with confirmed Noonan syndrome and profound sensorineural
      hearing impairment. INTERVENTIONS: Diagnostic and review of the literature.
      RESULTS: Five patients presented with profound sensorineural hearing impairment
      and molecularly confirmed Noonan syndrome. Sensorineural hearing impairment has
      been progressive for three patients. Cardiac echography identified pulmonary
      stenosis in two patients and was normal for the three other patients. Short
      stature was found in two patients. Mild intellectual disability was found in one
      patient. Inconspicuous clinical features as facial dysmorphism, cryptorchidism,
      or easy bruising were of peculiar interest to reach the diagnosis of Noonan
      syndrome. CONCLUSION: Profound sensorineural hearing impairment can be the main
      feature of Noonan syndrome. Associated features are highly variable; thus,
      detailed medical history and careful physical examination are mandatory to
      consider the diagnosis in case of a sensorineural hearing impairment.

PMID- 28742630
TI  - Unique Case of Hearing Recovery After Otic Capsule Destruction and Complete
      Sensorineural Hearing Loss Caused by Langerhans Cell Histiocytosis.
AB  - : A 14-year-old woman presented with right-sided otologic and vestibular symptoms
      after presenting with hormonal disturbances earlier that year. Imaging showed a
      gross destruction of the temporal bone, mastoid air cells, and external acoustic
      meatus with invasion into the otic capsule. The patient experienced complete
      sensorineural hearing loss in the right ear. Biopsy diagnosed Langerhans cell
      histiocytosis (LCH) and the patient was treated with chemotherapy. After 1 year
      of treatment, the patient's hearing partially recovered and imaging showed
      reconstitution of the temporal bone including the otic capsule. Our case is the
      first report of complete sensorineural hearing loss with partial recovery after
      LCH treatment.

PMID- 28742631
TI  - Vestibular Function in Adults With Epilepsy of Unknown Etiology.
AB  - OBJECTIVE: This study aimed to evaluate vestibular function in adults with
      chronic epilepsy of unknown etiology in the inter-ictal period. BACKGROUND:
      Epilepsy is a chronic medical disorder. Life-long therapy may be required in one
      third of patients. Epilepsy is associated with comorbid somatic conditions which
      impairs patients' quality of life. METHODS: This cross-sectional study included
      28 with generalized tonic clonic (GTC) convulsions and 14 and 3 with temporal
      (TLE) and frontal lobe (FLE) epilepsies with secondary generalization (all were
      on regular carbamazepine therapy) and 40 healthy control subjects. The patients'
      mean age was 34.97 +/- 7.35 years and the duration of illness was 18.75 +/- 7.99
      years. All underwent videonystagmography (VNG). RESULTS: Compared with controls,
      patients had frequent vestibular symptoms including dizziness (62.22%) (p =
      0.0001) and sense of imbalance (44.44%) (p = 0.0001). Eleven patients (24.44%)
      had central vestibular dysfunction (p = 0.0001); 9 (20%) had mixed vestibular
      dysfunction and one (2.22%) had peripheral vestibular dysfunction (p = 0.0001).
      Abnormalities were observed in saccadic (44.4%) and pursuit (42.2%) eye
      movements, optokinetic nystagmus (42.2%) and positioning/positional (11.11%) and
      caloric (13.33%) testing. TLE and FLE were associated with more VNG abnormalities
      than GTC. No significant differences were observed in the demographic and
      clinical characteristics between patients with and without VNG abnormalities.
      CONCLUSION: Vestibular manifestations are frequent in patients with epilepsy.
      This may be a result of the permanent damaging effect of chronic epilepsy on the
      vestibular cortical areas and/or a toxic effect from prolonged carbamazepine
      therapy on the peripheral and central vestibular systems.

PMID- 28742632
TI  - The Middle Ear Cleft Status in a "Natural" Cohort With Eustachian Tube
      Dysfunction.
AB  - BACKGROUND: The Eustachian tube (ET) has a major role in the middle ear (ME)
      pressure homeostasis. ET dysfunction is the accepted paradigm for pressure
      related ME disorders. We studied the ME status in patients with severely
      diminished ET opening abilities, and anticipated to find ME disorders in most of
      them. PATIENTS AND METHODS: ME status was evaluated in unconscious adults, who
      were hospitalized in a rehabilitation center with severe brain damage, requiring
      tracheotomy and gastrostomy. These patients were unable to swallow, produce
      valsalva, yawn, and needed oral suctioning. Examination included fiberoptic
      nasopharyngoscopy, gag reflex and soft palate assessments, otoscopy, and
      tympanometry. RESULTS: Nineteen patients (38 ears) were evaluated: 14 men and 5
      women, aged 18 to 93 years (average 59). Duration of gastrostomy and tracheotomy
      were between 3 months and 18 years. All the patients lacked gag reflex, palatal
      movements, or supraglottic sensation. Eighteen ears (47%) had otitis media with
      effusion (OME) (versus ~3% in the general population, p = 0.00001), none had
      significant tympanic membrane atelectasis, but 20 (53%) ears were normal. Twenty
      two ears (59%) had tympanometry types B/C and 16 (41%) had type A. Cerumen
      impaction incidence (26 ears, 68%) was significantly higher than in normal adults
      (10%), mentally retarded (36%), and nursing homes residents (57%). CONCLUSIONS: A
      dysfunctional ET predisposed ME disorders. Yet, ~50% of the ears were normal, in
      contrast to the current paradigm. This implies that ME pressure homeostasis is
      maintained by factors that can compensate for ET dysfunction. Treating cerumen
      impaction and OME may be beneficial for rehabilitation.

PMID- 28742633
TI  - Stable Longitudinal Performance of Adult Cochlear Implant Users for More Than 10
      Years.
AB  - OBJECTIVE: To analyze the long-term performance of cochlear implant patients.
      STUDY DESIGN: Retrospective longitudinal study. SETTING: Tertiary referral center
      with a large cochlear implant program. MAIN OUTCOME MEASURE: Speech perception
      scores in quiet and in background noise in the short-term (1.12 +/- 0.15 yr) and
      long-term (12.61 +/- 2.34 yr) after implantation. PATIENTS: Fifty-eight implanted
      ears from 55 patients with a mean age of 51.80 +/- 1.757 years at the time of
      implantation were included. RESULTS: Speech perception scores were stable in the
      long-term for up to 20 years postimplantation. When alteration of speech
      perception over time was investigated in relation to the age at implantation,
      there was a deterioration of the scores in quiet in older patients (>60 years old
      at the time of surgery). In addition the speech comprehension in noise was
      negatively correlated with the age at the time of the test. CONCLUSION: The
      speech perception abilities of cochlear implant users are stable in the long-term
      and at the most may be affected by the age of the patients, as it is known from
      acoustic hearing.

PMID- 28742634
TI  - Fingolimod (FTY-720) is Capable of Reversing Tumor Necrosis Factor Induced
      Decreases in Cochlear Blood Flow.
AB  - HYPOTHESIS: The potential of Fingolimod (FTY-720), a sphingosine-1-phosphate
      analogue, to revoke the changes in cochlear blood flow induced by tumor necrosis
      factor (TNF) was investigated. BACKGROUND: Impairment of cochlear blood flow has
      often been considered as the common final pathway of various inner ear
      pathologies. TNF, an ubiquitous cytokine, plays a major role in these
      pathologies, reducing cochlear blood flow via sphingosine-1-phosphate-signaling.
      METHODS: Fifteen Dunkin-Hartley guinea pigs were randomly assigned to one of
      three groups (placebo/placebo, TNF/placebo, TNF/FTY-720). Cochlear
      microcirculation was quantified over 60 minutes by in vivo fluorescence
      microscopy before and after topical application of placebo or TNF (5 ng/ml) and
      after subsequent application of placebo or FTY-720 (200 MUg/ml). RESULTS:
      Treatment with TNF led to a significant decrease of cochlear blood flow.Following
      this, application of placebo caused no significant changes while application of
      FTY-720 caused a significant rise in cochlear blood flow. CONCLUSIONS: FTY-720 is
      capable of reversing changes in cochlear blood flow induced by application of
      TNF. This makes FTY-720 a valid candidate for potential treatment of numerous
      inner ear pathologies.

PMID- 28742635
TI  - Long Exercise Test in the Interattack Period of Periodic Paralysis: A Useful and
      Sensitive Diagnostic Tool.
AB  - PURPOSE: The reference values of long exercise test are inconsistent in previous
      studies. Our research aims to determine the reference values and improve
      diagnostic efficiency of long exercise test in periodic paralysis. METHODS: In
      this study, 100 healthy controls, 35 non-periodic paralysis patients, and 47
      patients with periodic paralysis were recruited. The procedures of long exercise
      test were conducted following McMannis(1986) method. RESULTS: The decrease rate
      in compound muscle action potential amplitudes was correlated with gender, and it
      was not influenced by age, height, weight, and exercise. After analyzing receiver
      operating characteristic curves, the compound muscle action potential amplitude
      decrease rate was stratified by sex. The mean area under the curve, sensitivity,
      and specificity were higher in male and female than all pooled subjects. The
      reference values of compound muscle action potential amplitude decrease rate were
      46.8% in male and 26.9% in female, respectively. CONCLUSIONS: The long exercise
      test is a useful and sensitive diagnostic tool for primary periodic paralysis and
      thyrotoxic periodic paralysis. However, the reference values should be set by
      sex, which has better diagnostic performance, sensitivity, and specificity.

PMID- 28742636
TI  - The Influence of Chloride for the Interpretation of Plasma Bicarbonate During the
      Treatment of Diabetic Ketoacidosis.
AB  - INTRODUCTION: Hyperchloremic metabolic acidosis can occur in diabetic
      ketoacidosis (DKA) and may affect the acid-base interpretation during treatment.
      OBJECTIVES: This study aims to describe the prevalence of hyperchloremia during
      the treatment of DKA and its effect on the interpretation of bicarbonate value.
      METHODS: A cross-sectional study, including all cases of DKA in patients aged 1
      to 18 years old admitted from 2010 to 2015, was performed. Laboratory tests were
      performed on admission (baseline), 2 and 6 hours after admission, and when
      resolution of DKA was achieved. Adjusted bicarbonate value was calculated using
      regression equations. RESULTS: Seventy-nine DKA episodes were included. The
      average age was 13.3 +/- 3.8 years. Baseline levels were as follows: plasma
      glucose, 479 +/- 133 mg/dL; pH 7.1 +/- 0.083; bicarbonate, 9.65 +/- 2.9; and
      anion gap, 23.9 +/- 7.5. The time to achieve resolution of DKA was 12.2 +/- 4.4
      hours, and the decrease in capillary glucose was 25.5 (19.7-38.2) mg/dL per hour.
      After 6 hours of treatment, the proportion of patients presenting hyperchloremia
      increased from 23% to 77%. By using adjusted bicarbonate, the percentage of
      patients achieving resolution of DKA after 6 hours of treatment would have been
      35.4% (confidence interval 95%, 28-49), in comparison with 24.1% (confidence
      interval 95%, 18-37) using observed bicarbonate (P = 0.004). CONCLUSIONS: The
      hyperchloremia developed during the treatment of DKA could modify the value of
      measured plasma bicarbonate concentration and unnecessarily prolong the initial
      phase of treatment.

PMID- 28742637
TI  - Is Intussusception a Middle-of-the-Night Emergency?
AB  - OBJECTIVES: Intussusception is the most common abdominal emergency in pediatric
      patients aged 6 months to 3 years. There is often a delay in diagnosis, as the
      presentation can be confused for viral gastroenteritis. Given this scenario, we
      questioned the practice of performing emergency reductions in children during the
      night when minimal support staff are available. Pneumatic reduction is not a
      benign procedure, with the most significant risk being bowel perforation. We
      performed this analysis to determine whether it would be safe to delay reduction
      in these patients until normal working hours when more support staff are
      available. METHODS: We performed a retrospective review of intussusceptions
      occurring between January 2010 and May 2015 at 2 tertiary care institutions. The
      medical record for each patient was evaluated for age at presentation, sex, time
      of presentation to clinician or the emergency department, and time to reduction.
      The outcomes of attempted reduction were documented, as well as time to surgery
      and surgical findings in applicable cases. A Wilcoxon rank test was used to
      compare the median time with nonsurgical intervention among those who did not
      undergo surgery to the median time to nonsurgical intervention among those who
      ultimately underwent surgery for reduction. Multivariable logistic regression was
      used to test the association between surgical intervention and time to
      nonsurgical reduction, adjusting for the age of patients. RESULTS: The median
      time to nonsurgical intervention was higher among patients who ultimately
      underwent surgery than among those who did not require surgery (17.9 vs 7.0
      hours; P < 0.0001). The time to nonsurgical intervention was positively
      associated with a higher probability of surgical intervention (P = 0.002).
      CONCLUSIONS: Intussusception should continue to be considered an emergency, with
      nonsurgical reduction attempted promptly as standard of care.

PMID- 28742638
TI  - Extraocular Muscle Findings in Myasthenia Gravis Associated Treatment-Resistant
      Ophthalmoplegia.
AB  - We report the histopathological and ultrastructural tissue analysis of
      extraocular muscle (EOM) obtained from a patient with seronegative myasthenia
      gravis (MG) with treatment-resistant ophthalmoplegia for 3.5 years. The EOM
      demonstrated predominantly myopathic features and ultrastructural evidence of
      mitochondrial dysfunction, but the most striking features were increased
      endomysial collagen and adipocyte replacement of muscle fibers. By contrast,
      control EOM from a patient undergoing strabismus surgery for a sensory exotropia
      in a nonseeing eye and a similar duration of deviation, showed normal muscle
      histology. Although the histopathological and ultrastructural findings largely
      resemble those of limb muscle in MG, the abundant endomysial collagen may be
      nonspecific and secondary to poor force generation as a result of chronic
      ophthalmoplegia.

PMID- 28742639
TI  - Idiopathic Intracranial Hypertension Progressing to Venous Sinus Thrombosis,
      Subarachnoid Hemorrhage, and Stroke.
AB  - Idiopathic intracranial hypertension (IIH) is a syndrome characterized by
      increased intracranial pressure (ICP), the absence of structural lesions on
      neuroimaging, and normal cerebrospinal fluid composition. Cerebral venous sinus
      thrombosis (CVST) is a common cause of increased ICP and can be differentiated
      from IIH with magnetic resonance venography. We describe a young woman with
      typical IIH who underwent lumbar puncture and was treated with a short course of
      high-dose corticosteroids followed by acetazolamide. She subsequently developed
      CVST, subarachnoid hemorrhage, and stroke. Risk factors that may have resulted in
      CVST are discussed.

PMID- 28742640
TI  - Role of Nocturnal Arterial Hypotension in Nonarteritic Anterior Ischemic Optic
      Neuropathy.

PMID- 28742641
TI  - Does Nocturnal Hypotension Play a Causal Role in Nonarteritic Anterior Ischemic
      Optic Neuropathy?: Response.

PMID- 28742642
TI  - Pathway for the Management of Sleep Apnea in the Cardiac Patient.
AB  - Sleep-disordered breathing is a highly prevalent medical condition, which if
      undiagnosed leads to increased morbidity and mortality, particularly related to
      increased incidence of cardiovascular events. It is therefore imperative that we
      identify patient population at high risk for sleep apnea and refer them to the
      appropriate therapy as early as possible. Up-to-date there is no management
      guideline specifically geared towards cardiac patients. Thus, we propose a (SAP)
      Sleep Apnea Pathway to correctly identify and triage these patients to the
      appropriate therapy.

PMID- 28742643
TI  - Sensitive Troponin I and Stress Testing in the Emergency Department for the Early
      Management of Chest Pain Using 2-Hour Protocol.
AB  - BACKGROUND: Despite improvements in identifying high-risk patients with non-ST
      segment ACS (acute coronary syndrome), low risk patients presenting with atypical
      chest pain and non-diagnostic Electrocardiogram (ECG) continued to undergo
      unnecessary admissions and testing. Since 1992, our chest pain protocol included
      using 4-hour serial biomarkers from ED admission in combination with stress
      testing to evaluate these patients. Our study aimed at determining whether a new
      accelerated diagnostic protocol using sensitive cardiac troponin I (cTnI) 2 hours
      after admission to the ED followed by stress testing is safe and effective in
      emergency settings, allowing for appropriate triage, earlier discharge and
      reducing costs. METHODS: We conducted a single center randomized trial at
      Presence St. Francis Hospital Chest pain center in Evanston, Illinois enrolling
      sixty-four consecutive patients with atypical chest pain and non-diagnostic ECG,
      participants were randomized to accelerated 2 hrs protocol or our pre-existing 4
      hrs protocol. Sixty patients completed the protocol and were randomized to either
      a 2-hour (29 patients) or 4-hour protocol using both I-STAT and PATHFAST cTnI (31
      Patients). Troponin I was evaluated at 0 and at 2 hours from ED presentation with
      and additional draw for patients in the 4-hour rule out-group. Patients with
      normal serial biomarkers were then evaluated with stress testing and qualified
      for earlier discharge if the stress test was negative, while those with a
      positive biomarker at any time were admitted. Thirty-six patients had exercise
      treadmill stress test and 24 patients had either nuclear or Echo stress test.
      RESULTS: Fifty-three patients had a normal stress test and were discharged home.
      One patient in the 4-hour group with normal serial troponins developed
      ventricular tachycardia/fibrillation during the recovery period of a regular
      stress test. Six patients had a positive PATHFAST cTnI and a normal I-STAT cTnI
      at 2-hours. Two out of these six patients evaluated by coronary angiography. One
      patient had severe tortuous coronaries but no significant obstructive lesion and
      one had a severe CAD who needed Coronary artery bypass grafting (CABG). Three of
      the six patients had a normal stress test and one patient decided to leave
      without further testing. None of the patients with a normal stress test had a
      major cardiac event or adverse cardiac outcome at six-month follow up.
      CONCLUSION: This study demonstrates that the 2 hours accelerated protocol using
      high sensitivity Troponin assay at 0 and 2 hours with comprehensive clinical
      evaluation and ECG followed by stress testing might be successful in identifying
      low-risk patient population who may benefit from early discharge from ED reducing
      associated costs and length of stay.

PMID- 28742644
TI  - Update on SGLT2 Inhibitors-New Data Released at the American Diabetes
      Association.
AB  - Sodium-glucose cotransporter 2 (SGLT2) inhibitors are one of the newer classes of
      antiglycemic agents approved for the management of patients with type 2 diabetes
      mellitus. Due to their unique mechanism of action, SGLT2 inhibitors have shown to
      be beneficial beyond glucose control. The improvement in cardiovascular (CV)
      outcomes was first observed in the landmark EMPA-REG OUTCOMES study. Following
      these results, numerous CV outcome trials were designed to identify whether the
      beneficial CV and renal effects observed with empagliflozin are unique or a drug
      class effect. The benefit of SGLT2 inhibition was confirmed by the CANagliflozin
      cardioVascular Assessment Study (CANVAS) Program, presented at the American
      Diabetes Association 77th Scientific Sessions. With over 10,000 patients, the
      CANVAS Program integrated data from two large CV outcome studies. Canagliflozin
      achieved a 14% reduction in the composite endpoint of CV mortality, nonfatal
      myocardial infarction (MI), or nonfatal stroke, and a 33% reduction in the risk
      of hospitalization for heart failure (HF) compared with placebo. Potential renal
      protective effects were also observed with canagliflozin; however, an increased
      risk of amputation with canagliflozin was seen in both CANVAS studies. The class
      effect of SGLT2 inhibitors was also confirmed in new analyses of the The
      Comparative Effectiveness of Cardiovascular Outcomes (CVD-REAL) study, which
      aimed to evaluate SGLT2 inhibitors (dapagliflozin, canagliflozin, and
      empagliflozin) in broader patient populations with type 2 diabetes mellitus. In
      patients who were new to SGLT2 inhibitors, significant reductions in rates of CV
      death and hospitalization for HF were observed compared with any other glucose
      lowering agents. SGLT2 inhibitors were also associated with lower rates in
      hospitalization for HF in patients with and without CV disease. In addition,
      substudies of the EMPA-REG OUTCOME trial further provided insight on the efficacy
      of empagliflozin across categories of adjusted control of blood pressure, low
      density lipoprotein cholesterol, and hemoglobin A1c (HbA1c) over time.

PMID- 28742645
TI  - Quality Improvement in Management of Acute Coronary Syndrome: Continuing Medical
      Education and Peer Coaching Improve Antiplatelet Medication Adherence and Reduce
      Hospital Readmissions.
AB  - BACKGROUND: Reducing hospital readmissions and improving patient adherence to
      antiplatelet medications after an acute coronary syndrome (ACS) event are
      important goals for improving patient health and decreasing healthcare costs.
      Nearly half of patients will have a secondary event within 1 year of the initial
      ACS event. Quality improvement (QI) initiatives that include continuing medical
      education and peer coaching may improve physician practice patterns and,
      therefore, patient outcomes. METHODS: This study evaluated the impact of a QI
      initiative on antiplatelet (P2Y12 inhibitor) medication adherence (measured via
      pharmacy fill rates postdischarge) and hospital readmissions. RESULTS: Notable
      physician performance and patient-level changes included significant increases in
      antiplatelet medication counseling at hospital discharge (30%-57%; P < 0.0001),
      in P2Y12 inhibitor prescribing at hospital discharge (76%-84%; P = 0.02), and in
      patient fill rates for branded P2Y12 inhibitors (72%-100%; P = 0.0001). There
      were numerical trends toward lower rates of ACS-related rehospitalizations at 60
      days postdischarge (from 11% to 7%; P = 0.15) and of all-cause rehospitalizations
      at 60 days (from 20% to 14%; P = 0.10). CONCLUSION: Important in the rapidly
      evolving landscape of quality healthcare, QI involving continuing medical
      education and peer coaching demonstrably impacted physician performance and
      patient outcomes after an ACS event.

PMID- 28742646
TI  - Comparison of 3 Symptom Classification Methods to Standardize the History
      Component of the HEART Score.
AB  - OBJECTIVES: The History, Electrocardiography, Age, Risk factors, Troponin (HEART)
      score enables rapid risk stratification of emergency department patients
      presenting with chest pain. However, the subjectivity in scoring introduced by
      the history component has been criticized by some clinicians. We examined the
      association of 3 objective scoring models with the results of noninvasive cardiac
      testing. METHODS: Medical records for all patients evaluated in the chest pain
      center of an academic medical center during a 1-year period were reviewed
      retrospectively. Each patient's history component score was calculated using 3
      models developed by the authors. Differences in the distribution of HEART scores
      for each model, as well as their degree of agreement with one another, as well as
      the results of cardiac testing were analyzed. RESULTS: Seven hundred forty nine
      patients were studied, 58 of which had an abnormal stress test or computed
      tomography coronary angiography. The mean HEART scores for models 1, 2, and 3
      were 2.97 (SD 1.17), 2.57 (SD 1.25), and 3.30 (SD 1.35), respectively, and were
      significantly different (P < 0.001). However, for each model, the likelihood of
      an abnormal cardiovascular test did not correlate with higher scores on the
      symptom component of the HEART score (P = 0.09, 0.41, and 0.86, respectively).
      CONCLUSIONS: While the objective scoring models produced different distributions
      of HEART scores, no model performed well with regards to identifying patients
      with abnormal advanced cardiac studies in this relatively low-risk cohort.
      Further studies in a broader cohort of patients, as well as comparison with the
      performance of subjective history scoring, is warranted before adoption of any of
      these objective models.

PMID- 28742647
TI  - The (Dis) Utility of a Change in Troponin I for Diagnosis of Non-ST-Segment
      Elevation Myocardial Infarction in an Observation Unit.
AB  - BACKGROUND: Observation units (OUs) may be an efficient and effective setting to
      diagnose and risk stratify patients with coronary ischemia and myocardial
      infarction (MI). Given improved cardiac troponin I (cTnI) assays and expanded
      utilization of OUs, it is not uncommon for patients with mildly elevated cTnI to
      be evaluated in OUs. We investigated the serial cTnI results in OU patients to
      determine whether absolute or relative cTnI changes were useful for the diagnosis
      of MI. METHODS: This was a retrospective study of 260 patients placed in the OU
      from a single center in 2007, with an initial cTnI in the indeterminate range of
      0.04-0.2 ng/ml (Siemens ultrasensitive), and a second cTnI was drawn at 6 hours.
      The diagnosis of MI was determined based on the third universal definition of MI
      by consensus review of 2 cardiologists, with adjudication by a third cardiologist
      in case of disagreement. RESULTS: Of the 260 patients, 25 (9.6%) were determined
      to have MI at OU presentation. The optimal absolute and relative change in cTnI
      for MI diagnosis by receiver operating characteristic curve analysis were 0.02
      ng/ml and 40%, respectively. There was initial cardiologist disagreement in 60%
      (15/25) of MI cases despite full review of serial cTnI and cardiac testing
      results. At 30 days, there were 3 adverse events: 2 deaths and 1 MI. CONCLUSIONS:
      The diagnosis of MI in OU with low-level cTnI elevation is problematic.
      Furthermore, there is only marginal diagnostic utility of serial changes in cTnI
      in this patient population.

PMID- 28742648
TI  - Vitamin D Deficiency, Supplementation, and Cardiovascular Health.
AB  - Vitamin D has been traditionally recognized as a vitamin quintessential for bone
      mineral health. In the past 2 decades, numerous experimental and observational
      studies have highlighted the role of vitamin D in immunity, metabolic syndrome
      (obesity and diabetes), cancers, renal disease, memory, and neurological
      dysfunction. In this article, we review important studies that focused on the
      impact of vitamin D on blood pressure, myocardial infarction, peripheral arterial
      disease, heart failure, and statin intolerance. Amidst the current pool of
      ambiguous evidence, we intend to discuss the role of vitamin D in "high-value
      cardiovascular health care".

PMID- 28742649
TI  - Thoracoscopic Implantation of an Array Electrode in the Pericardium Transverse
      Sinus to Reduce Defibrillation Threshold.
AB  - Among the implantable cardioverter defibrillator recipients, there is still a
      subgroup of patients in whom the defibrillation threshold is too high and the
      maximal shock output of the implantable cardioverter defibrillator can fail to
      terminate a ventricular arrhythmia. We report a new thoracoscopic minimally
      invasive approach to place a standard array electrode in the transverse
      pericardial sinus of a patient implanted with a cardiac resynchronization and
      defibrillation therapy device with persistent high defibrillation threshold. This
      approach was developed to achieve very low shock impedance with a consequent
      increase in the current flow and reduction of defibrillation threshold.

PMID- 28742650
TI  - Reliable and Easy-To-Use Liquid Chromatography-Tandem Mass Spectrometry Method
      for Simultaneous Analysis of Fluconazole, Isavuconazole, Itraconazole, Hydroxy
      Itraconazole, Posaconazole, and Voriconazole in Human Plasma and Serum.
AB  - BACKGROUND: A fast and easy-to-use liquid chromatography-tandem mass spectrometry
      method for the determination and quantification of 6 triazoles [fluconazole
      (FLZ), isavuconazole (ISZ), itraconazole (ITZ), hydroxy-itraconazole (OH-ITZ),
      posaconazole (PSZ), and voriconazole (VRZ)] in human plasma and serum was
      developed and validated for therapeutic drug monitoring. METHODS: Sample
      preparation was based on protein precipitation with acetonitrile and subsequent
      centrifugation. Isotope-labeled analogues for each analyte were used as internal
      standards. Chromatographic separation was achieved using a 50 * 2.1 mm, 1.9 MUm
      polar Hypersil Gold C18 column and mobile phase consisting of 0.1% formic
      acid/acetonitrile (45%/55%, vol/vol) at a flow rate of 340 MUL/min. The triazoles
      were simultaneously detected using a triple-stage quadrupole mass spectrometer
      operated in selected reaction monitoring mode with positive heated electrospray
      ionization within a single runtime of t = 3.00 minutes. RESULTS: Linearity of all
      azole concentration ranges was verified by the Mandel test and demonstrated for
      all azoles. All calibration curves were linear and fitted using least squares
      regression with a weighting factor of the reciprocal concentration. Limits of
      detection (MUg/L/L) were FLZ, 9.3; ISZ, 0.3; ITZ, 0.6; OH-ITZ, 8.6; PSZ, 3.4; and
      VRZ, 2.1. The lower limits of quantitation (MUg/L/liter) were FLZ, 28.3; ISZ,
      1.0; ITZ, 1.7; OH-ITZ, 26.2; PSZ, 10.3; and VRZ, 6.3. Intraday and interday
      precisions ranged from 0.6% to 6.6% for all azoles. Intraday and interday
      accuracies (%bias) of all analytes were within 10.5%. In addition, we report on a
      29-year-old white woman (94 kg body weight) with a history of acute myeloid
      leukemia who underwent stem cell transplantation. Because of diagnosis of
      aspergillus pneumonia, antifungal pharmacotherapy was initiated with different
      application modes and dosages of ISZ, and plasma concentrations were monitored
      over a time period of 6 months. CONCLUSIONS: A precise and highly sensitive
      liquid chromatography-tandem mass spectrometry method was developed that enables
      quantification of triazoles in plasma and serum matrix across therapeutically
      relevant concentration ranges. It was successfully implemented in our therapeutic
      drug monitoring routine service and is suitable for routine monitoring of
      antifungal therapy and in severely ill patients.

PMID- 28742651
TI  - Interpregnancy Interval and Adverse Pregnancy Outcomes: An Analysis of Successive
      Pregnancies and: Interpregnancy Interval and Pregnancy Outcomes: Causal or Not?

PMID- 28742652
TI  - In Reply.

PMID- 28742653
TI  - Interpregnancy Interval and Adverse Pregnancy Outcomes: An Analysis of Successive
      Pregnancies.

PMID- 28742654
TI  - Interpregnancy Interval and Adverse Pregnancy Outcomes: An Analysis of Successive
      Pregnancies.

PMID- 28742655
TI  - Consensus Bundle on Maternal Mental Health: Perinatal Depression and Anxiety.

PMID- 28742656
TI  - In Reply.

PMID- 28742657
TI  - Consensus Bundle on Maternal Mental Health: Perinatal Depression and Anxiety.

PMID- 28742658
TI  - In Reply.

PMID- 28742659
TI  - Laparoscopy Compared With Laparotomy for Debulking Ovarian Cancer After
      Neoadjuvant Chemotherapy.

PMID- 28742660
TI  - In Reply.

PMID- 28742661
TI  - Association Between Senior Obstetrician Supervision of Resident Deliveries and
      Mode of Delivery.

PMID- 28742662
TI  - In Reply.

PMID- 28742665
TI  - Table of Contents for Online Material in the August 2017 Issue.

PMID- 28742667
TI  - Practice Bulletin No. 181 Summary: Prevention of Rh D Alloimmunization.
AB  - Advances in the prevention and treatment of Rh D alloimmunization have been one
      of the great success stories of modern obstetrics. There is wide variation in
      prevalence rates of Rh D-negative individuals between regions, for example from
      5% in India to 15% in North America (1). However, high birth rates in low
      prevalence areas means Rh hemolytic disease of the newborn is still an important
      cause of morbidity and mortality in countries without prophylaxis programs (1).
      In such countries, 14% of affected fetuses are stillborn and one half of live
      born infants suffer neonatal death or brain injury (1). The routine use of Rh D
      immune globulin is responsible for the reduced rate of red cell alloimmunization
      in more economically developed countries. First introduced in the 1970s, the
      postpartum administration of Rh D immune globulin reduced the rate of
      alloimmunization in at-risk pregnancies from approximately 13-16% to
      approximately 0.5-1.8% (2, 3). The risk was further reduced to 0.14-0.2% with the
      addition of routine antepartum administration (2, 3). Despite considerable proof
      of efficacy, there are still a large number of cases of Rh D alloimmunization
      because of failure to follow established protocols. In addition, there are new
      data to help guide management, especially with regard to weak D phenotype women.
      The purpose of this document is to provide evidence-based guidance for the
      management of patients at risk of Rh D alloimmunization.

PMID- 28742668
TI  - Committee Opinion No. 709 Summary: Commercial Enterprises in Medical Practice.
AB  - Monetary reimbursement of physicians in exchange for medical advice and treatment
      is well established and accepted in medical practice. However, financial
      pressures and the pervasiveness of entrepreneurial values have led some
      physicians to widen the scope of activities for which they seek reimbursement.
      Some of these commercial activities are ethically problematic in the clinical
      setting. Obstetrician-gynecologists should strive to ensure that commercial
      enterprises in medical practice do not compromise the patient-focused mission of
      clinical care. In this Committee Opinion, the American College of Obstetricians
      and Gynecologists' Committee on Ethics differentiates between commercial
      activities judged to be generally ethically appropriate for obstetrician
      gynecologists and those that are not.

PMID- 28742669
TI  - Committee Opinion No. 710 Summary: Counseling Adolescents About Contraception.
AB  - Modern contraceptives are very effective when used correctly and, thus, effective
      counseling regarding contraceptive options and provision of resources to increase
      access are key components of adolescent health care. Regardless of a patient's
      age or previous sexual activity, the obstetrician-gynecologist routinely should
      address her contraceptive needs, expectations, and concerns. Obstetrician
      gynecologists should be aware of and be prepared to address the most common
      misperceptions about contraceptive methods in a way that is age appropriate and
      compatible with the patient's health literacy. The American College of
      Obstetricians and Gynecologists recommends that discussions about contraception
      begin with information on the most effective methods first. Emergency
      contraception routinely should be included in discussions about contraception,
      including access issues. Moreover, the American College of Obstetricians and
      Gynecologists recommends that obstetrician-gynecologists work with their office
      staff to establish office procedures and routines that safeguard the privacy of
      adolescent patients whenever possible. Adolescents' right of refusal for
      initiating or discontinuing a method should be addressed by obstetrician
      gynecologists. At no time should an adolescent patient be forced to use a method
      chosen by someone other than herself, including a parent, guardian, partner, or
      health care provider. The initial encounter and follow-up visits should include
      continual reassessment of sexual concerns, behavior, relationships, prevention
      strategies, and testing and treatment for sexually transmitted infections per the
      Centers for Disease Control and Prevention's guidelines.

PMID- 28742670
TI  - Committee Opinion No. 711 Summary: Opioid Use and Opioid Use Disorder in
      Pregnancy.
AB  - Opioid use in pregnancy has escalated dramatically in recent years, paralleling
      the epidemic observed in the general population. To combat the opioid epidemic,
      all health care providers need to take an active role. Pregnancy provides an
      important opportunity to identify and treat women with substance use disorders.
      Substance use disorders affect women across all racial and ethnic groups and all
      socioeconomic groups, and affect women in rural, urban, and suburban populations.
      Therefore, it is essential that screening be universal. Screening for substance
      use should be a part of comprehensive obstetric care and should be done at the
      first prenatal visit in partnership with the pregnant woman. Patients who use
      opioids during pregnancy represent a diverse group, and it is important to
      recognize and differentiate between opioid use in the context of medical care,
      opioid misuse, and untreated opioid use disorder. Multidisciplinary long-term
      follow-up should include medical, developmental, and social support. Infants born
      to women who used opioids during pregnancy should be monitored for neonatal
      abstinence syndrome by a pediatric care provider. Early universal screening,
      brief intervention (such as engaging a patient in a short conversation, providing
      feedback and advice), and referral for treatment of pregnant women with opioid
      use and opioid use disorder improve maternal and infant outcomes. In general, a
      coordinated multidisciplinary approach without criminal sanctions has the best
      chance of helping infants and families.

PMID- 28742671
TI  - Committee Opinion No. 712 Summary: Intrapartum Management of Intraamniotic
      Infection.
AB  - Intraamniotic infection, also known as chorioamnionitis, is an infection with
      resultant inflammation of any combination of the amniotic fluid, placenta, fetus,
      fetal membranes, or decidua. Intraamniotic infection is a common condition noted
      among preterm and term parturients. However, most cases of intraamniotic
      infection detected and managed by obstetrician-gynecologists or other obstetric
      care providers will be noted among term patients in labor. Intraamniotic
      infection can be associated with acute neonatal morbidity, including neonatal
      pneumonia, meningitis, sepsis, and death. Maternal morbidity from intraamniotic
      infection also can be significant, and may include dysfunctional labor requiring
      increased intervention, postpartum uterine atony with hemorrhage, endometritis,
      peritonitis, sepsis, adult respiratory distress syndrome and, rarely, death.
      Recognition of intrapartum intraamniotic infection and implementation of
      treatment recommendations are essential steps that effectively can minimize
      morbidity and mortality for women and newborns. Timely maternal management
      together with notification of the neonatal health care providers will facilitate
      appropriate evaluation and empiric antibiotic treatment when indicated.
      Intraamniotic infection alone is rarely, if ever, an indication for cesarean
      delivery.

PMID- 28742672
TI  - Committee Opinion No. 713 Summary: Antenatal Corticosteroid Therapy for Fetal
      Maturation.
AB  - Corticosteroid administration before anticipated preterm birth is one of the most
      important antenatal therapies available to improve newborn outcomes. A single
      course of corticosteroids is recommended for pregnant women between 24 0/7 weeks
      and 33 6/7 weeks of gestation who are at risk of preterm delivery within 7 days,
      including for those with ruptured membranes and multiple gestations. It also may
      be considered for pregnant women starting at 23 0/7 weeks of gestation who are at
      risk of preterm delivery within 7 days, based on a family's decision regarding
      resuscitation, irrespective of membrane rupture status and regardless of fetal
      number. Administration of betamethasone may be considered in pregnant women
      between 34 0/7 weeks and 36 6/7 weeks of gestation who are at risk of preterm
      birth within 7 days, and who have not received a previous course of antenatal
      corticosteroids. A single repeat course of antenatal corticosteroids should be
      considered in women who are less than 34 0/7 weeks of gestation who are at risk
      of preterm delivery within 7 days, and whose prior course of antenatal
      corticosteroids was administered more than 14 days previously. Rescue course
      corticosteroids could be provided as early as 7 days from the prior dose, if
      indicated by the clinical scenario. Continued surveillance of long-term outcomes
      after in utero corticosteroid exposure should be supported. Quality improvement
      strategies to optimize appropriate and timely antenatal corticosteroid
      administration are encouraged.

PMID- 28742673
TI  - Practice Bulletin No. 181: Prevention of Rh D Alloimmunization.
AB  - Advances in the prevention and treatment of Rh D alloimmunization have been one
      of the great success stories of modern obstetrics. There is wide variation in
      prevalence rates of Rh D-negative individuals between regions, for example from
      5% in India to 15% in North America (1). However, high birth rates in low
      prevalence areas means Rh hemolytic disease of the newborn is still an important
      cause of morbidity and mortality in countries without prophylaxis programs (1).
      In such countries, 14% of affected fetuses are stillborn and one half of live
      born infants suffer neonatal death or brain injury (1). The routine use of Rh D
      immune globulin is responsible for the reduced rate of red cell alloimmunization
      in more economically developed countries. First introduced in the 1970s, the
      postpartum administration of Rh D immune globulin reduced the rate of
      alloimmunization in at-risk pregnancies from approximately 13-16% to
      approximately 0.5-1.8% (2, 3). The risk was further reduced to 0.14-0.2% with the
      addition of routine antepartum administration (2, 3). Despite considerable proof
      of efficacy, there are still a large number of cases of Rh D alloimmunization
      because of failure to follow established protocols. In addition, there are new
      data to help guide management, especially with regard to weak D phenotype women.
      The purpose of this document is to provide evidence-based guidance for the
      management of patients at risk of Rh D alloimmunization.

PMID- 28742674
TI  - Committee Opinion No. 709: Commercial Enterprises in Medical Practice.
AB  - Monetary reimbursement of physicians in exchange for medical advice and treatment
      is well established and accepted in medical practice. However, financial
      pressures and the pervasiveness of entrepreneurial values have led some
      physicians to widen the scope of activities for which they seek reimbursement.
      Some of these commercial activities are ethically problematic in the clinical
      setting. Obstetrician-gynecologists should strive to ensure that commercial
      enterprises in medical practice do not compromise the patient-focused mission of
      clinical care. In this Committee Opinion, the American College of Obstetricians
      and Gynecologists' Committee on Ethics differentiates between commercial
      activities judged to be generally ethically appropriate for obstetrician
      gynecologists and those that are not.

PMID- 28742675
TI  - Committee Opinion No. 710: Counseling Adolescents About Contraception.
AB  - Modern contraceptives are very effective when used correctly and, thus, effective
      counseling regarding contraceptive options and provision of resources to increase
      access are key components of adolescent health care. Regardless of a patient's
      age or previous sexual activity, the obstetrician-gynecologist routinely should
      address her contraceptive needs, expectations, and concerns. Obstetrician
      gynecologists should be aware of and be prepared to address the most common
      misperceptions about contraceptive methods in a way that is age appropriate and
      compatible with the patient's health literacy. The American College of
      Obstetricians and Gynecologists recommends that discussions about contraception
      begin with information on the most effective methods first. Emergency
      contraception routinely should be included in discussions about contraception,
      including access issues. Moreover, the American College of Obstetricians and
      Gynecologists recommends that obstetrician-gynecologists work with their office
      staff to establish office procedures and routines that safeguard the privacy of
      adolescent patients whenever possible. Adolescents' right of refusal for
      initiating or discontinuing a method should be addressed by obstetrician
      gynecologists. At no time should an adolescent patient be forced to use a method
      chosen by someone other than herself, including a parent, guardian, partner, or
      health care provider. The initial encounter and follow-up visits should include
      continual reassessment of sexual concerns, behavior, relationships, prevention
      strategies, and testing and treatment for sexually transmitted infections per the
      Centers for Disease Control and Prevention's guidelines.

PMID- 28742676
TI  - Committee Opinion No. 711: Opioid Use and Opioid Use Disorder in Pregnancy.
AB  - Opioid use in pregnancy has escalated dramatically in recent years, paralleling
      the epidemic observed in the general population. To combat the opioid epidemic,
      all health care providers need to take an active role. Pregnancy provides an
      important opportunity to identify and treat women with substance use disorders.
      Substance use disorders affect women across all racial and ethnic groups and all
      socioeconomic groups, and affect women in rural, urban, and suburban populations.
      Therefore, it is essential that screening be universal. Screening for substance
      use should be a part of comprehensive obstetric care and should be done at the
      first prenatal visit in partnership with the pregnant woman. Patients who use
      opioids during pregnancy represent a diverse group, and it is important to
      recognize and differentiate between opioid use in the context of medical care,
      opioid misuse, and untreated opioid use disorder. Multidisciplinary long-term
      follow-up should include medical, developmental, and social support. Infants born
      to women who used opioids during pregnancy should be monitored for neonatal
      abstinence syndrome by a pediatric care provider. Early universal screening,
      brief intervention (such as engaging a patient in a short conversation, providing
      feedback and advice), and referral for treatment of pregnant women with opioid
      use and opioid use disorder improve maternal and infant outcomes. In general, a
      coordinated multidisciplinary approach without criminal sanctions has the best
      chance of helping infants and families.

PMID- 28742677
TI  - Committee Opinion No. 712: Intrapartum Management of Intraamniotic Infection.
AB  - Intraamniotic infection, also known as chorioamnionitis, is an infection with
      resultant inflammation of any combination of the amniotic fluid, placenta, fetus,
      fetal membranes, or decidua. Intraamniotic infection is a common condition noted
      among preterm and term parturients. However, most cases of intraamniotic
      infection detected and managed by obstetrician-gynecologists or other obstetric
      care providers will be noted among term patients in labor. Intraamniotic
      infection can be associated with acute neonatal morbidity, including neonatal
      pneumonia, meningitis, sepsis, and death. Maternal morbidity from intraamniotic
      infection also can be significant, and may include dysfunctional labor requiring
      increased intervention, postpartum uterine atony with hemorrhage, endometritis,
      peritonitis, sepsis, adult respiratory distress syndrome and, rarely, death.
      Recognition of intrapartum intraamniotic infection and implementation of
      treatment recommendations are essential steps that effectively can minimize
      morbidity and mortality for women and newborns. Timely maternal management
      together with notification of the neonatal health care providers will facilitate
      appropriate evaluation and empiric antibiotic treatment when indicated.
      Intraamniotic infection alone is rarely, if ever, an indication for cesarean
      delivery.

PMID- 28742678
TI  - Committee Opinion No. 713: Antenatal Corticosteroid Therapy for Fetal Maturation.
AB  - Corticosteroid administration before anticipated preterm birth is one of the most
      important antenatal therapies available to improve newborn outcomes. A single
      course of corticosteroids is recommended for pregnant women between 24 0/7 weeks
      and 33 6/7 weeks of gestation who are at risk of preterm delivery within 7 days,
      including for those with ruptured membranes and multiple gestations. It also may
      be considered for pregnant women starting at 23 0/7 weeks of gestation who are at
      risk of preterm delivery within 7 days, based on a family's decision regarding
      resuscitation, irrespective of membrane rupture status and regardless of fetal
      number. Administration of betamethasone may be considered in pregnant women
      between 34 0/7 weeks and 36 6/7 weeks of gestation who are at risk of preterm
      birth within 7 days, and who have not received a previous course of antenatal
      corticosteroids. A single repeat course of antenatal corticosteroids should be
      considered in women who are less than 34 0/7 weeks of gestation who are at risk
      of preterm delivery within 7 days, and whose prior course of antenatal
      corticosteroids was administered more than 14 days previously. Rescue course
      corticosteroids could be provided as early as 7 days from the prior dose, if
      indicated by the clinical scenario. Continued surveillance of long-term outcomes
      after in utero corticosteroid exposure should be supported. Quality improvement
      strategies to optimize appropriate and timely antenatal corticosteroid
      administration are encouraged.

PMID- 28742679
TI  - Delayed treatment of a posterior cruciate ligament tibial insertion avulsion
      fracture in a child with open physis: a case report with a 4-year follow-up.
AB  - Posterior cruciate ligament avulsion fracture from its tibial insertion is a rare
      pathology in children. It is usually caused by high-energy traumas and its
      diagnosis is not always easy. Late diagnosis leads to late treatment, which can
      result in suboptimal results. We present a case of a 13-year-old boy hit by a
      car, who had a delay in diagnosis and treatment because of severe head trauma.
      The patient was treated 4 months after the trauma with open reduction and
      internal fixation of the avulsion fracture. After 4 years of follow-up, he has no
      complaints and has achieved good functional outcome.

PMID- 28742680
TI  - Individualized Metabolic Surgery Score: Procedure Selection Based on Diabetes
      Severity.
AB  - OBJECTIVE: To construct and validate a scoring system for evidence-based
      selection of bariatric and metabolic surgery procedures according to severity of
      type 2 diabetes (T2DM). BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve
      gastrectomy (SG) account for >95% of bariatric procedures in United States in
      patients with T2DM. To date, there is no validated model to guide procedure
      selection based on long-term glucose control in patients with T2DM. METHODS: A
      total of 659 patients with T2DM who underwent RYGB and SG at an academic center
      in the United States and had a minimum 5-year follow-up (2005-2011) were analyzed
      to generate the model. The validation dataset consisted of 241 patients from an
      academic center in Spain where similar criteria were applied. RESULTS: At median
      postoperative follow-up of 7 years (range 5-12), diabetes remission (HbA1C <6.5%
      off medications) was observed in 49% after RYGB and 28% after SG (P < 0.001).
      Four independent predictors of long-term remission including preoperative
      duration of T2DM (P < 0.0001), preoperative number of diabetes medications (P <
      0.0001), insulin use (P = 0.002), and glycemic control (HbA1C < 7%) (P = 0.002)
      were used to develop the Individualized Metabolic Surgery (IMS) score using a
      nomogram. Patients were then categorized into 3 stages of diabetes severity. In
      mild T2DM (IMS score <=25), both procedures significantly improved T2DM. In
      severe T2DM (IMS score >95), when clinical features suggest limited functional
      beta-cell reserve, both procedures had similarly low efficacy for diabetes
      remission. There was an intermediate group, however, in which RYGB was
      significantly more effective than SG, likely related to its more pronounced
      neurohormonal effects. Findings were externally validated and procedure
      recommendations for each severity stage were provided. CONCLUSIONS: This is the
      largest reported cohort (n = 900) with long-term postoperative glycemic follow
      up, which, for the first time, categorizes T2DM into 3 validated severity stages
      for evidence-based procedure selection.

PMID- 28742681
TI  - Targeting Value-Driven Quality Improvement for Laparoscopic Cholecystectomy in
      Michigan.
AB  - OBJECTIVE: The purpose of this study was to evaluate complete episode
      expenditures for laparoscopic cholecystectomy, a common and lower-risk operation,
      to characterize novel targets for value-based quality improvement. SUMMARY
      BACKGROUND DATA: Despite enthusiasm for improving the overall value of surgical
      care, most efforts have focused on high-risk inpatient surgery. METHODS: We
      identified 19,213 patients undergoing elective laparoscopic cholecystectomy from
      2012 to 2015 using data from Medicare and a large private payer. We calculated
      price-standardized payments for the entire surgical episode of care and
      stratified patients by surgeon. We used linear regression to risk- and
      reliability-adjusted expenditures for patient characteristics, diagnoses, and the
      use of additional procedures. RESULTS: Fully adjusted total episode costs varied
      2.4-fold across surgeons ($7922-$17,500). After grouping surgeons by adjusted
      total episode payments, each component of the total episode was more expensive
      for patients treated by the most expensive versus the least expensive quartile of
      surgeons. For example, payments for physician services were higher for the most
      expensive surgeons [$1932, 95% confidence interval (CI) $1844-$2021] compared to
      least expensive surgeons ($1592, 95% CI $1450-$1701, P < 0.01). Overall
      differences were driven by higher rates of complications (10% vs. 5%) and
      readmissions (14% vs. 8%), and lower rates of ambulatory procedures (77% vs. 56%)
      for surgeons with the highest versus lowest expenditures. Projections showed that
      a 10% increase ambulatory operations would yield $3.6 million in annual savings
      for beneficiaries. CONCLUSIONS: Episode payments for laparoscopic cholecystectomy
      vary widely across surgeons. Although improvements in several domains would
      reduce expenditures, efforts to expand ambulatory surgical practices may result
      in the largest savings to beneficiaries in Michigan.

PMID- 28742682
TI  - Ductal Carcinoma In Situ and Margins <2 mm: Contemporary Outcomes With Breast
      Conservation.
AB  - OBJECTIVE: To determine the relationship between negative margin width and
      locoregional recurrence (LRR) in a contemporary cohort of ductal carcinoma in
      situ (DCIS) patients. BACKGROUND: Recent national consensus guidelines recommend
      an optimal margin width of 2 mm or greater for the management of DCIS; however,
      controversy regarding re-excision remains when managing negative margins <2 mm.
      METHODS: One thousand four hundred ninety-one patients with DCIS who underwent
      breast-conserving surgery from 1996 to 2010 were identified from a prospectively
      managed cancer center database and analyzed using univariate and multivariate Cox
      proportional hazard models to determine the relationship between negative margin
      width and LRR with or without adjuvant radiation therapy (RT). RESULTS: A
      univariate analysis revealed that age <40 years (n = 89; P = 0.02), no RT (n =
      298; P = 0.01), and negative margin width <2 mm (n = 120; P = 0.005) were
      associated with LRR. The association between margin width and LRR differed by
      adjuvant RT status (interaction P = 0.02). There was no statistical significant
      difference in LRR between patients with <2 mm and >=2 mm negative margins who
      underwent RT (10-yr LRR rate, 4.8% vs 3.3%, respectively; hazard ratio, 0.8; 95%
      CI, 0.2-3.2; P = 0.72). For patients who did not undergo RT, those with margins
      <2 mm were significantly more likely to develop a LRR than were those with
      margins >=2 mm (10-yr LRR rate, 30.9% vs 5.4%, respectively; hazard ratio, 5.5;
      95% CI, 1.8-16.8, P = 0.003). CONCLUSIONS: Routine additional surgery may not be
      justified for patients with negative margins <2 mm who undergo RT but should be
      performed in patients who forego RT.

PMID- 28742683
TI  - Centralize Pancreatic Surgery Now!

PMID- 28742684
TI  - Endovascular Repair of Abdominal Aortic Aneurysm in Patients Physically
      Ineligible for Open Repair: Very Long-term Follow-up in the EVAR-2 Randomized
      Controlled Trial.
AB  - OBJECTIVE: The aim of the study was to compare long-term total and aneurysm
      related mortality in physically frail patients with abdominal aortic aneurysm
      (AAA) randomized to either early endovascular aneurysm repair (EVAR) or no
      intervention. SUMMARY BACKGROUND DATA: EVAR-2 remains the sole randomized trial
      to identify whether EVAR reduces mortality in patients physically ineligible for
      open repair. METHODS: Between September 1999 and August 2004, 404 patients from
      33 centers in the United Kingdom aged >=60 years with AAA >5.5 cm in diameter
      were randomized 1:1 using computer-generated sequences of randomly permuted
      blocks stratified by center to receive either EVAR (197) or no-intervention
      (207). The primary analysis compared total and aneurysm-related deaths in groups
      until June 30, 2015 (mean, 12.0 yrs; maximum 14.1 yrs). RESULTS: Mean follow-up
      until death or censoring was 4.2 years. There were 187 deaths (22.6 per 100
      person-yrs) in the EVAR group and 194 (22.1 per 100 person-yrs) in the no
      intervention group. By 12 years of follow-up the estimated survival was 5.3% [95%
      confidence interval (CI), 2.6-9.2] in the EVAR group and 8.5% (95% CI, 5.2-12.9)
      in the no-intervention group; there was no significant difference in life
      expectancy between the groups (both 4.2 yrs; P = 0.97). However, overall aneurysm
      related mortality was significantly lower in the EVAR group [3.3 deaths per 100
      person-yrs compared with 6.5 deaths per 100 person-yrs in the no-intervention
      group, adjusted hazard ratio 0.55 (95% CI, 0.34-0.91; P = 0.019)]. Patients
      surviving beyond 8 years were younger, with higher body mass index, estimated
      glomerular filtration rate, and forced expiratory volume in 1 second.
      CONCLUSIONS: EVAR does not increase overall life expectancy in patients
      ineligible for open repair, but can reduce aneurysm-related mortality.

PMID- 28742685
TI  - Recurrence Patterns and Long-Term Results After Induction Chemotherapy,
      Chemoradiotherapy, and Curative Surgery in Patients With Locally Advanced
      Esophageal Cancer.
AB  - OBJECTIVE: The long-term follow up data of 2 prospective phase II trials is
      reported (NCT00072033, NCT00445861), which investigated neoadjuvant
      chemoradiation followed by surgery in patients with esophageal carcinoma.
      Postoperative complications as well as prognostic factors and patterns of relapse
      during long-term observation are shown. SUMMARY OF BACKGROUND DATA: Long-term
      follow-up is often missing in the complex setting of multimodal treatments of
      esophageal carcinoma; this leads to rather undifferentiated follow-up guidelines
      for this tumor entity. METHODS: In the first trial, patients received induction
      chemotherapy followed by chemoradiation and surgery. In the second trial,
      cetuximab was added to the same neoadjuvant treatment concomitant with induction
      chemotherapy and chemoradiation. RESULTS: Eighty-two patients underwent surgery;
      the median follow-up time was 6.8 and 6.4 years, respectively. Fifty-five percent
      were diagnosed with adenocarcinoma, 80% clinically node-positive, 68% received
      transthoracic esophagectomy, and 32% transhiatal or transmediastinal resection.
      Five patients died postoperatively in-hospital due to complications (6%). The
      median overall survival was 4.3 years, and the median event-free survival was 2.7
      years. Patients with adenocarcinoma rarely relapsed after a 3-year event-free
      survival. Whereas patients with residual tumor cells after neoadjuvant therapy
      primarily experienced relapse within the first 2 postoperative years, this in
      contrast to several patients with complete remission who also experienced late
      relapses 4 years after surgery. CONCLUSION: After curative surgery in a
      multimodal setting, the histological type and the response to neoadjuvant therapy
      predicted the time frame of relapse; this knowledge may influence further follow
      up guidelines for esophageal carcinoma.

PMID- 28742686
TI  - Bioengineering a Human Face Graft: The Matrix of Identity.
AB  - OBJECTIVE: During the last decade, face allotransplantation has been shown to be
      a revolutionary reconstructive procedure for severe disfigurements. However,
      offer to patients remains limited due to lifelong immunosuppression. To move
      forward in the field, a new pathway in tissue engineering is proposed.
      BACKGROUND: Our previously reported technique of matrix production of a porcine
      auricular subunit graft has been translated to a human face model. METHODS: 5
      partial and 1 total face grafts were procured from human fresh cadavers. After
      arterial cannulation, the specimens were perfused using a combined
      detergent/polar solvent decellularization protocol. Preservation of vascular
      patency was assessed by imaging, cell and antigen removal by DNA quantification
      and histology. The main extracellular matrix proteins and associated cytokines
      were evaluated. Lip scaffolds were cultivated with dermal, muscle progenitor and
      endothelial cells, either on discs or in a bioreactor. RESULTS: Decellularization
      was successful in all facial grafts within 12 days revealing acellular scaffolds
      with full preservation of innate morphology. Imaging demonstrated a preservation
      of the entire vascular tree patency. Removal of cells and antigens was confirmed
      by reduction of DNA and antigen markers negativation. Microscopic evaluation
      revealed preservation of tissue structures as well as of major proteins. Seeded
      cells were viable and well distributed within all scaffolds. CONCLUSIONS: Complex
      acellular facial scaffolds were obtained, preserving simultaneously a cell
      friendly extracellular matrix and a perfusable vascular tree. This step will
      enable further engineering of postmortem facial grafts, thereby offering new
      perspectives in composite tissue allotransplantation.

PMID- 28742687
TI  - The Allosteric Hemoglobin Effector ITPP Inhibits Metastatic Colon Cancer in Mice.
AB  - OBJECTIVE: To test the effects of enhanced intracellular oxygen contents on the
      metastatic potential of colon cancer. BACKGROUND: Colorectal cancer is the
      commonest gastrointestinal carcinoma. Distant metastases occur in half of
      patients and are responsible for most cancer-related deaths. Tumor hypoxia is
      central to the pathogenesis of metastases. Myo-Inositoltrispyrophosphate (ITPP),
      a nontoxic, antihypoxic compound, has recently shown significant benefits in
      experimental cancer, particularly when combined with standard chemotherapy.
      Whether ITPP protects from distant metastases in primary colon cancer is unknown.
      METHODS: ITPP alone or combined with FOLFOX was tested in a mouse model with
      cecal implantation of green fluorescent protein-labeled syngeneic colorectal
      cancer cells. Tumor development was monitored through longitudinal magnetic
      resonance imaging-based morphometric analysis and survival. Established serum
      markers of tumor spread were measured serially and circulating tumor cells were
      detected via fluorescence measurements. RESULTS: ITPP significantly reduced the
      occurrence of metastases as well as other indicators of tumor aggressiveness.
      Less circulating tumor cells along with reduction in malignant serum markers
      (osteopontin, Cxcl12) were noted. The ITPP benefits also affected the primary
      cancer site. Importantly, animals treated with ITPP had a significant survival
      benefit compared with respective controls, while a combination of FOLFOX with
      ITPP conferred the maximum benefits, including dramatic improvements in survival
      (mean 86 vs 188 d). CONCLUSIONS: Restoring oxygen in metastatic colon cancer
      through ITPP inhibits tumor spread and markedly improves animal survival; an
      effect that is enhanced through the application of subsequent chemotherapy. These
      promising novel findings call for a clinical trial on ITPP in patients with
      colorectal cancer, which is under way.

PMID- 28742688
TI  - "Physician Heal Thyself" Isn't Working.

PMID- 28742689
TI  - Lymphangiogenic Gene Expression Is Associated With Lymph Node Recurrence and Poor
      Prognosis After Partial Hepatectomy for Colorectal Liver Metastasis.
AB  - OBJECTIVES: To investigate the relevance of lymphangiogenic gene expression in
      primary and liver metastasis of colorectal cancer (CRC) and identify determinants
      of lymphatic invasion. BACKGROUND: Lymphatic development promoting vascular
      endothelial growth factor C (VEGFC) is associated with poor outcome in primary
      CRC. For colorectal liver metastasis (CRLM), intrahepatic lymph invasion and
      lymph node metastasis are poor prognostic factors. Exact biological factors
      promoting lymphatic involvement remain elusive, just as the association with
      molecular subtypes of CRC. METHODS: We designed a lymphangiogenic gene set
      (VEGFC, Nrp-2, PDPN, LYVE-1, MRC1, CCL-21) and applied it to large datasets of
      CRC. Gene expression of the lymphangiogenic signature was assessed in resected
      CRLM specimens by Rt-QPCR. In vitro experiments were performed with colon cancer
      cell line Colo320 (high Nrp-2 expression) and human dermal microvascular
      lymphatic endothelial cells (LECs). RESULTS: Lymphangiogenic gene expression was
      associated with poor prognosis in both primary and liver metastasis of CRC. CRLM
      with high expression of consensus molecular subtype-4 identifier genes also
      exhibited high lymphangiogenic gene expression. Lymph node recurrence following
      CRLM resection was associated with high expression of VEGFC and Nrp-2. Blocking
      Nrp-2 significantly reduced invasion of Colo320 cells through an LEC monolayer.
      CONCLUSIONS: Lymphangiogenic gene expression is correlated with worse prognosis
      and consensus molecular subtype-4 in both primary and liver metastatic CRC. VEGFC
      and Nrp-2 expression may be predictive of lymph node involvement in recurrence
      after resection of CRLM. Nrp-2, expressed on both tumor and LECs, may have a
      mechanistic role in lymphatic invasion and is a potential novel target in CRC.

PMID- 28742690
TI  - Do Surgeons React?: A Retrospective Analysis of Surgeons' Response to Harassment
      of a Colleague During Simulated Operating Theatre Scenarios.
AB  - OBJECTIVE: To assess and report on surgeons' ability to identify and manage
      incidences of harassment. BACKGROUND: The Royal Australasian College of Surgeons
      is committed to driving out discrimination, bullying, harassment, and sexual
      harassment from surgical training and practice, through changing the culture of
      the workplace. To eradicate these behaviors, it is first critical to understand
      how the current workforce responds to these actions. METHODS: A retrospective
      analysis of video data of an operating theatre simulation was conducted to
      identify how surgeons, from a range of experience levels, react to instances of
      harassment. Thematic analysis was used to categorize types of harassment and
      participant response characteristics. The frequency of these responses was
      assessed and reported. RESULTS: The type of participant response depended on the
      nature of harassment being perpetuated and the seniority of the participant. In
      the 50 instances of scripted harassment, active responses were enacted 52% of the
      time, acknowledgment responses 16%, and no response enacted in 30%. One senior
      surgeon also perpetuated the harassment (2%). Trainees were more likely to
      respond actively compared with consultants. CONCLUSION: It is apparent that
      trainees are more aware of instances of harassment, and were more likely to
      intervene during the simulated scenario. However, a large proportion of
      harassment was unchallenged. The hierarchical nature of surgical education and
      the surgical workforce in general needs to enable a culture in which the
      responsibility to intervene is allowed and respected. Simulation-based education
      programs could be developed to train in the recognition and intervention of
      discrimination, bullying, harassment and sexual harassment.

PMID- 28742691
TI  - Impact of Lymph Node Yield on Overall Survival in Patients Treated With
      Neoadjuvant Chemoradiotherapy Followed by Esophagectomy for Cancer: A Population
      based Cohort Study in the Netherlands.
AB  - OBJECTIVE: To evaluate the impact of lymph node yield (LNY) on survival in
      patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by
      esophagectomy for cancer. BACKGROUND: The value of an extended lymphadenectomy
      after nCRT for esophageal cancer is debated. Recent reports demonstrate no
      association between LNY and survival. This association has not yet been evaluated
      in larger cohorts. METHODS: All patients who underwent nCRT followed by
      esophagectomy between 2005 and 2014 were identified from the Netherlands Cancer
      Registry. The association between LNY and overall survival was analyzed using
      multivariable Cox regression analyses, adjusting for diagnosis year, referral,
      hospital volume, age, sex, malignancy history, tumor location, histology, cTN
      stage, surgical approach, radicality, and ypTN-stage. Analyses were performed
      with LNY as categorized predictor (<15 vs >=15 nodes) and continuous predictor
      (per 10 additionally nodes). RESULTS: A total of 2698 patients were included with
      a median overall survival of 34 months (range 4-143). A higher LNY was
      significantly associated with improved overall survival, both as categorized
      predictor (hazard ratio 0.77, 95% confidence interval 0.68-0.86) and as
      continuous predictor (hazard ratio 0.84, 95% confidence interval 0.78-0.90).
      Furthermore, a higher LNY was associated with favorable hazard ratios across
      subgroups, including both squamous cell carcinoma and adenocarcinoma, both cN0
      and cN+, both transthoracic and transhiatal approaches, and both ypN0 and ypN+.
      CONCLUSIONS: This large population-based cohort study demonstrates an association
      between LNY and overall survival, indicating a therapeutic value of extended
      lymphadenectomy during esophagectomy. Therefore, an extended lymphadenectomy
      should be the standard of care after nCRT.

PMID- 28742692
TI  - Oncologic Outcome and Morbidity in the Elderly Rectal Cancer Patients After
      Preoperative Chemoradiotherapy and Total Mesorectal Excision: A Multi
      institutional and Case-matched Control Study.
AB  - OBJECTIVE: To determine the toxicity and oncologic outcome of neoadjuvant
      chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME) in
      the elderly (>=70 yrs) and younger (<70 yrs) rectal cancer patients. BACKGROUND:
      Sufficient data for elderly rectal cancer patients who received definitive
      trimodality have not been accumulated yet. PATIENTS AND METHODS: A total of 1232
      rectal cancer patients who received neoadjuvant CRT and TME were enrolled in this
      study. After propensity-score matching, 310 younger patients and 310 elderly
      patients were matched with 1:1 manner. Treatment response, toxicity, surgical
      outcome, recurrence, and survival were assessed and compared between the 2 groups
      of patients. RESULTS: The median age was 58 years for the younger patient group
      and 74 years for the elderly group. Pathologic complete response rates were not
      significantly different between the 2 groups (younger and elderly: 17.1% vs
      14.8%, P = 0.443). The 5-year recurrence-free survival (younger and elderly:
      67.7% vs 65.5%, P = 0.483) and overall survival (younger and elderly: 82.9% vs.
      79.5%, P = 0.271) rates were not significantly different between the 2 groups
      either. Adjuvant chemotherapy after surgery was less frequently delivered to the
      elderly than that to younger patients (83.9% vs 69.0%). Grade 3 or higher acute
      hematologic toxicity was observed more frequently in the elderly than that in the
      younger group (9.0% vs 16.1%, P = 0.008). Late complication rate was higher in
      the elderly group compared with that in the younger group without statistical
      significance (2.6% vs 4.5%, P = 0.193). CONCLUSIONS: Although acute hematologic
      toxicity was observed more frequently in the elderly patients than that in the
      younger patients, elderly rectal cancer patients with good performance status who
      received preoperative CRT and TME showed favorable tumor response and recurrence
      free survival similar to younger patients.

PMID- 28742693
TI  - Response to: "Carotid Endarterectomy Versus Stenting to Treat Carotid Stenosis:
      There is More to Than Meets the Eye".

PMID- 28742694
TI  - Reducing the Burden of Catastrophic Health Expenditures in the United States.

PMID- 28742695
TI  - Does Surgeon Sex Matter?: Practice Patterns and Outcomes of Female and Male
      Surgeons.
AB  - OBJECTIVE: We sought to compare postoperative outcomes of female surgeons (FS)
      and male surgeons (MS) within general surgery. SUMMARY OF BACKGROUND DATA: FS in
      the workforce are increasing in number. Female physicians provide exceptional
      care in other specialties. Differences in surgical outcomes of FS and MS have not
      been examined. METHODS: We linked the AMA Physician Masterfile to discharge
      claims from New York, Florida, and Pennsylvania (2012 to 2013) to examine
      practice patterns and to compare surgical outcomes of FS and MS. We paired FS and
      MS operating at the same hospital using cardinality matching with refined balance
      and compared inpatient mortality, any postoperative complication, and prolonged
      length of stay (pLOS) in FS and MS. RESULTS: Overall practice patterns differed
      between the 663 FS and 3219 MS. We identified 2462 surgeons (19% FS, 81% MS) at
      429 hospitals who met inclusion criteria for outcomes analysis. FS were younger
      (mean age +/- SD FS: 48.5 +/- 8.4 years, MS: 54.3 +/- 9.4y; P < 0.001) with less
      clinical experience (mean years +/- SD FS: 11.6 +/- 8.3 y, MS: 17.6 +/- 10.0
      years; P < 0.001) than MS before matching. FS had lower rates of inpatient
      mortality (FS: 1.51%, MS: 2.30%; P < 0.001), any postoperative complication (FS:
      12.6%, MS: 16.1%; P < 0.001), and pLOS (FS: 18.4%, MS: 20.7%; P < 0.001) before
      matching. After matching, FS and MS outcomes were equivalent. CONCLUSION: Surgeon
      practice patterns vary by sex and experience. FS and MS with similar
      characteristics who treat similar patients at the same hospital have equivalent
      rates of inpatient morality, postoperative complications, and prolonged length of
      hospital stay. Patients should select the surgeon who is the best fit for them
      regardless of sex.

PMID- 28742696
TI  - Transanal Versus Transabdominal Minimally Invasive (Completion) Proctectomy With
      Ileal Pouch-anal Anastomosis in Ulcerative Colitis: A Comparative Study.
AB  - OBJECTIVE: This study aims to compare surgical outcome of transanal ileal pouch
      anal anastomosis (ta-IPAA) with transabdominal minimal invasive approach in
      ulcerative colitis (UC), using the comprehensive complication index (CCI).
      BACKGROUND: Recent evolutions in rectal cancer surgery led to transanal
      dissection of the rectum resulting in a better exposure of the distal rectum and
      presumed better outcome. The same approach was introduced for patients with UC,
      resulting in decreased invasiveness. METHODS: All patients, undergoing minimally
      invasive restorative proctocolectomy in 1, 2, or 3 stages between January 2011
      and September 2016 in 3 referral centers were included. Only patients who
      underwent either multiport, single port, single port with 1 additional port, hand
      assisted, or robotic (R) laparoscopy were included in the analysis. CCI,
      registered during 90 days after pouch construction, was compared between the
      transanal and the transabdominal approach. RESULTS: Ninety-seven patients (male:
      52%) with ta-IPAA were compared to 119 (male: 53%) with transabdominal IPAA.
      Ninety-nine (46%) patients had a defunctioning ileostomy at time of pouch
      construction. A 2-step model showed that the odds for postoperative morbidity
      were 0.52 times lower in the ta-IPAA group (95% confidence interval [0.29; 0.92]
      P = 0.026). In patients with morbidity, mean CCI of the transanal approach was
      2.23 points lower than the transabdominal approach (95% confidence interval: [
      6.64-3.36] P = 0.13), which was not significant. CONCLUSIONS: Ta-IPAA for UC is a
      safe procedure, resulting in fewer patients with morbidity, but comparable CCI
      when morbidity is present. Overall, ta-IPAA led to lower CCI scores.

PMID- 28742697
TI  - Are Thoracotomy and/or Intrathoracic Anastomosis Still Predictors of
      Postoperative Mortality After Esophageal Cancer Surgery?: A Nationwide Study.
AB  - BACKGROUND: Intrathoracic (vs cervical) anastomosis and a thoracotomy (vs
      absence) have previously been associated with increasing postoperative mortality
      (POM). Recent improvements in surgical practices and perioperative management may
      have changed these dogmas. OBJECTIVES: The aim of this study was to evaluate the
      impact of performing intrathoracic anastomosis and/or thoracotomy on POM after
      esophageal cancer surgery in recent years. METHODS: All consecutive patients who
      underwent esophageal cancer surgery with reconstruction between 2010 and 2012 in
      France were included (n = 3286). Patients with a thoracoscopic approach were
      excluded (n = 4). We compared 30-day POM between patients having received
      intrathoracic (vs cervical) anastomosis and between those having received a
      thoracotomy or not. Multivariate analyses and propensity score matching were used
      to adjust for confounding factors. RESULTS: Patients had either cervical (n =
      548) or intrathoracic (n = 2738) anastomosis. Thirty-day POM was higher after
      cervical anastomosis (8.8% vs 4.9%, P < 0.001). Having received a thoracotomy (n
      = 3061) was associated with a decreased risk of 30-day POM (5.3% vs 9.3%, P =
      0.011). After adjustment for confounding factors, cervical anastomosis was
      associated with 30-day POM [odds ratio (OR) 1.71; 95% confidence interval (CI)
      1.05-2.77); P = 0.032], whereas performing a thoracotomy was not associated with
      30-day POM (OR 0.97; 95% CI 0.51-1.84; P = 0.926). CONCLUSIONS: Nowadays,
      intrathoracic anastomosis provides a lower 30-day POM rate compared to cervical
      anastomosis, and performing a thoracotomy is not associated with POM. Systematic
      anastomosis neck placement or thoracotomy avoidance is not a relevant argument
      anymore to decrease POM.

PMID- 28742698
TI  - Survival Benefit of Neoadjuvant Treatment in Clinical T3N0M0 Esophageal Cancer:
      Results From a Retrospective Multicenter European Study.
AB  - BACKGROUND: Based on current guidelines, clinical T3N0M0 esophageal tumors may or
      may not receive neoadjuvant treatment, according to their perception as locally
      advanced (cT3) or early-stage tumors (stage II). The study aim was to assess the
      impact of neoadjuvant treatment upon survival for cT3N0M0 esophageal cancer
      patients, with subgroup analyses by histological type (squamous cell carcinoma vs
      adenocarcinoma) and type of neoadjuvant treatment (chemotherapy vs
      radiochemotherapy). METHODS: Data from patients operated on for esophageal cancer
      in 30 European centers were collected. Among the 382 of 2944 patients with
      clinical T3N0M0 stage at initial diagnosis (13.0%), we compared those treated
      with primary surgery (S, n = 193) versus with neoadjuvant treatment plus surgery
      (NS, n = 189). RESULTS: The S and NS groups were similar regarding their
      demographic and surgical characteristics. In-hospital postoperative morbidity and
      mortality rates were comparable between groups. Patients were found to be pN+ in
      64.2% versus 42.9% in the S and NS groups respectively (P < 0.001), pN2/N3 in
      35.2% versus 21.2% (P < 0.001), stage 0 in 0% versus 16.4% (P < 0.001), and R0 in
      81.3% versus 89.4% of cases (P = 0.026). Median overall and disease-free
      survivals were significantly better in the NS group, 38.4 versus 27.9 months (P =
      0.007) and 31.6 versus 27.5 months (P = 0.040), respectively, and this difference
      remained for both histological types. Radiotherapy did not offer a benefit
      compared with chemotherapy alone (P = 0.687). In multivariable analysis,
      neoadjuvant treatment was an independent favorable prognostic factor (HR 0.76,
      95% CI 0.58-0.99, P = 0.044). CONCLUSION: Neoadjuvant treatment offers a
      significant survival benefit for clinical T3N0M0 esophageal cancer.

PMID- 28742699
TI  - Understanding and Resetting Radiation Sensitivity in Rectal Cancer.
AB  - OBJECTIVE: The aim of the study was to explore specific microRNAs (miRs) in
      rectal cancer that would predict response to radiation and identify target
      pathways that may be exploited for neoadjuvant therapies. SUMMARY BACKGROUND
      DATA: Chemoradiotherapy (CRT) response is a predictor of survival in rectal
      cancer. Studies have demonstrated changes in RNA expression correlate with
      chemoradiation sensitivity across cancers. METHODS: Forty-five rectal cancer
      patients, partial responders (PR = 18), nonresponders (NR = 13), and complete
      responders (CR = 14) to CRT, as defined by a tumor regression score, were
      examined. miRs differentially expressed, using NanoString microArray profiling,
      were validated with qPCR. We quantified 1 miR and its downstream targets in
      patient samples. Chemosensitivity was measured in HCT-116, a human colorectal
      carcinoma cell line, using inhibitors of SHP2 and RAF. RESULTS: miR-451a, 502-5p,
      223-3p, and 1246 were the most upregulated miRs (>1.5-fold change) in a
      NanoString profiling miR panel. qPCR revealed a decrease in expression of miR
      451a in NRs. EMSY and CAB39, both downstream targets of miR-451a and involved in
      carcinogenesis (shown in TCGA) were increased in NRs (qPCR). Both targets are
      associated with worse survival in colorectal cancer. Inhibition of miR-451a in
      HCT-116 cells significantly decreased cell proliferation with treatment of SHP2
      and RAF inhibitors. CONCLUSIONS: An integrated analysis of rectal cancer miRs may
      yield biomarkers of radioresistance and offer treatment targets for
      resensitization.

PMID- 28742700
TI  - Comparison of Postoperative Outcomes Between Donation After Circulatory Death and
      Donation After Brain Death Liver Transplantation Using the Comprehensive
      Complication Index.
AB  - OBJECTIVE: To test the total burden of complications in the early postoperative
      period after liver transplantation (LT) between donation after circulatory death
      (DCD) and donation after brain death (DBD) grafts with the novel Comprehensive
      Complication Index (CCI). BACKGROUND: LT is complex surgery and the increasing
      use of high-risk grafts is pressuring current postoperative outcomes. DCD grafts
      in particular are associated with ischemic-type biliary lesions (ITBL) with
      subsequent impaired graft survival rates. METHODS: Retrospective single-center
      study of all LT since the start of DCD program (2001-2015). CCI (at hospital
      discharge and after 6 months) was the result of all complications weighted by
      their Clavien-Dindo grade. A multiple logistic regression model was used to
      identify factors associated with a complex postoperative course (CCI at 6 months
      >60). RESULTS: In total, 441 cases were included: 115 DCD and 326 DBD grafts.
      Median in-hospital CCI was comparable for both groups (DCD 38.2; DBD 36.7; P =
      0.429). Six-month postoperative median CCI was significantly higher for DCD
      grafts (53.4 vs 47.2; P = 0.041). Moreover, more DCD recipients underwent
      retransplantation for ITBL in this period (4% vs 1%; P = 0.031). Logistic
      regression identified recipient BMI (P = 0.046), recipient warm ischemia time
      (odds ratio, OR, 1.032; 95% CI, 1.008-1.056; P = 0.008), and DCD graft (OR 3.913;
      95% CI 1.200-12.767; P = 0.024) as risk factors for a CCI >60. CONCLUSIONS: This
      analysis shows a comparable complication rate during the index hospital stay for
      DCD and DBD LT, but the CCI increases significantly for DCD recipients in 6
      months after transplantation. Reduction of biliary complications, especially
      ITBL, is needed to improve the outcomes for DCD grafts.

PMID- 28742701
TI  - Postoperative Delirium as a Target for Surgical Quality Improvement.
AB  - OBJECTIVE: To explore hospital-level variation in postoperative delirium using a
      multi-institutional data source. BACKGROUND: Postoperative delirium is closely
      related to serious morbidity, disability, and death in older adults. Yet,
      surgeons and hospitals rarely measure delirium rates, which limits quality
      improvement efforts. METHODS: The American College of Surgeons National Surgical
      Quality Improvement Program (ACS NSQIP) Geriatric Surgery Pilot (2014 to 2015)
      collects geriatric-specific variables, including postoperative delirium using a
      standardized definition. Hierarchical logistic regression models, adjusted for
      case mix [Current Procedural Terminology (CPT) code] and patient risk factors,
      yielded risk-adjusted and smoothed odds ratios (ORs) for hospital performance.
      Model performance was assessed with Hosmer-Lemeshow (HL) statistic and c
      statistics, and compared across surgical specialties. RESULTS: Twenty thousand
      two hundred twelve older adults (>=65 years) underwent inpatient operations at 30
      hospitals. Postoperative delirium occurred in 2427 patients (12.0%) with
      variation across specialties, from 4.7% in gynecology to 13.7% in cardiothoracic
      surgery. Hierarchical modeling with 20 risk factors (HL = 9.423, P = 0.31; c
      statistic 0.86) identified 13 hospitals as statistical outliers (5 good, 8 poor
      performers). Per hospital, the median risk-adjusted delirium rate was 10.4%
      (range 3.2% to 27.5%). Operation-specific risk and preoperative cognitive
      impairment (OR 2.9, 95% confidence interval 2.5-3.5) were the strongest
      predictors. The model performed well across surgical specialties (orthopedic,
      general surgery, and vascular surgery). CONCLUSION: Rates of postoperative
      delirium varied 8.5-fold across hospitals, and can feasibly be measured in
      surgical quality datasets. The model performed well with 10 to 12 variables and
      demonstrated applicability across surgical specialties. Such efforts are critical
      to better tailor quality improvement to older surgical patients.

PMID- 28742702
TI  - Trends on Axillary Surgery in Nondistant Metastatic Breast Cancer Patients
      Treated Between 2011 and 2015: A Dutch Population-based Study in the ACOSOG-Z0011
      and AMAROS Era.
AB  - OBJECTIVES: To evaluate patterns of care in axillary surgery for Dutch clinical
      T1-4N0M0 (cT1-4N0M0) breast cancer patients and to assess the effect of the
      American College for Surgeons Oncology Group (ACOSOG)-Z0011 and After Mapping of
      the Axilla: Radiotherapy Or Surgery (AMAROS) trial on axillary surgery patterns
      in Dutch cT1-2N0M0 sentinel node positive breast cancer patients. BACKGROUND:
      Since publication of the ACOSOG-Z0011 and AMAROS trial, omitting a completion
      axillary lymph node dissection (cALND) in sentinel node positive breast cancer
      patients is proposed in selected patients. METHODS: Data were obtained from the
      nationwide Nationaal Borstkanker Overleg Nederland breast cancer audit.
      Descriptive analyses were used to demonstrate trends in axillary surgery.
      Multivariable logistic regression analyses were used to identify factors
      associated with the omission of cALND in cT1-2N0M0 sentinel node-positive breast
      cancer patients. RESULTS: Between 2011 and 2015 in cT1-4N0M0 breast cancer
      patients, the use of sentinel lymph node biopsy as definitive axillary staging
      increased from 72% to 93%, and (c)ALND as definitive axillary staging decreased
      from 24% to 6% (P < 0.001). The use of cALND decreased from 75% to 17% in cT1-2N0
      sentinel node-positive patients (P < 0.001). Earlier year of diagnosis, lower
      age, primary mastectomy, invasive lobular subtype, increasing tumor grade, and
      treatment in a nonteaching hospital were associated with a lower probability of
      omitting cALND (P < 0.001). CONCLUSIONS: This study shows a trend towards less
      extensive axillary surgery in Dutch cT1-T4N0M0 breast cancer patients;
      illustrated by an overall increase of sentinel lymph node biopsy and decrease in
      cALND. Despite this trend, particularly noticed in cT1-2N0 sentinel node-positive
      patients after publication of the ACOSOG-Z0011 and AMAROS trial, variations in
      patterns of care in axillary surgery are still present.

PMID- 28742703
TI  - Organ Preservation in cT2N0 Rectal Cancer After Neoadjuvant Chemoradiation
      Therapy: The Impact of Radiation Therapy Dose-escalation and Consolidation
      Chemotherapy.
AB  - OBJECTIVE: To demonstrate the difference in organ-preservation rates and
      avoidance of definitive surgery among cT2N0 rectal cancer patients undergoing 2
      different chemoradiation (CRT) regimens. BACKGROUND: Patients with cT2N0 rectal
      cancer are more likely to develop complete response to neoadjuvant CRT. Organ
      preservation has been considered an alternative treatment strategy for selected
      patients. Radiation dose-escalation and consolidation chemotherapy have been
      associated with increased rates of response and may improve chances of organ
      preservation among these patients. METHODS: Patients with distal and
      nonmetastatic cT2N0 rectal cancer managed by neoadjuvant CRT were retrospectively
      reviewed. Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5-FU-based
      chemotherapy) were compared with those undergoing extended CRT (54 Gy and 6
      cycles of 5-FU-based chemotherapy). Patients were assessed for tumor response at
      8 to 10 weeks. Patients with complete clinical response (cCR) underwent organ
      preservation strategy ("Watch and Wait"). Patients were referred to salvage
      surgery in the event of local recurrence during follow-up. RESULTS: Thirty-five
      patients underwent standard and 46 patients extended CRT. Patients undergoing
      extended CRT were more likely to undergo organ preservation and avoid definitive
      surgical resection at 5years (67% vs 30%; P = 0.001). After development of a cCR,
      surgery-free survival is similar between extended and standard CRT groups at 5
      years (78% vs 56%; P = 0.12). CONCLUSIONS: Dose-escalation and consolidation
      chemotherapy leads to increased long-term organ-preservation rates among cT2N0
      rectal cancer. After achievement of a cCR, the risk for local recurrence and need
      for salvage surgery is similar, irrespective of the CRT regimen.

PMID- 28742705
TI  - Carotid Endarterectomy Versus Carotid Stenting to Treat Carotid Stenosis: There
      Is More to Than Meets the Eye.

PMID- 28742704
TI  - Racial/Ethnic Disparities in Longer-term Outcomes Among Emergency General Surgery
      Patients: The Unique Experience of Universally Insured Older Adults.
AB  - OBJECTIVES: To determine whether racial/ethnic disparities in 30/90/180-day
      mortality, major morbidity, and unplanned readmissions exist among universally
      insured older adult (>=65 years) emergency general surgery patients; vary by
      diagnostic category; and can be explained by variations in geography, teaching
      status, age-cohort, and a hospital's percentage of minority patients. SUMMARY OF
      BACKGROUND DATA: As the US population ages and discussions surrounding the
      optimal method of insurance provision increasingly enter into national debate,
      longer-term outcomes are of paramount concern. It remains unclear the extent to
      which insurance changes disparities throughout patients' postacute recovery
      period among older adults. METHODS: Survival analysis of 2008 to 2014 Medicare
      data using risk-adjusted Cox proportional-hazards models. RESULTS: A total of
      6,779,649 older adults were included, of whom 82.8% identified as non-Hispanic
      white (NHW), 9.2% non-Hispanic black (NHB), 5.6% Hispanic, and 1.5% non-Hispanic
      Asian (NHA). Relative to NHW patients, each group of minority patients was
      significantly less likely to die [30-day NHB vs NHW hazard ratio (95% confidence
      interval): 0.88 (0.86-0.89)]. Differences became less apparent as outcomes
      approached 180 days [180-day NHB vs NHW: 1.00 (0.98-1.02)]. For major morbidity
      and unplanned readmission, differences among NHW, Hispanic, and NHA patients were
      comparable. NHB patients did consistently worse. Efforts to explain the
      occurrence found similar trends across diagnostic categories, but significant
      differences in disparities attributable to geography and the other included
      factors that combined accounted for up to 50% of readmission differences between
      racial/ethnic groups. CONCLUSION: The study found an inversion of racial/ethnic
      mortality differences and mitigation of non-NHB morbidity/readmission differences
      among universally insured older adults that decreased with time. Persistent
      disparities among nonagenarian patients and hospitals managing a regionally large
      share of minority patients warrant particular concern.

PMID- 28742706
TI  - Response to: "Aspirin Therapy on Blood Transfusion in Noncardiac Surgery:
      Evidence From Quality Effect Model".

PMID- 28742707
TI  - Commentary on Brief Clinical Report: Reconstruction/Repair of Iatrogenic Biliary
      Injuries: Is the Robot Offering a New Option?

PMID- 28742708
TI  - Postoperative Outcomes of Minimally Invasive Gastrectomy Versus Open Gastrectomy
      During the Early Introduction of Minimally Invasive Gastrectomy in the
      Netherlands: A Population-based Cohort Study.
AB  - OBJECTIVE: To compare postoperative outcomes of minimally invasive gastrectomy
      (MIG) to open gastrectomy (OG) for cancer during the introduction of MIG in the
      Netherlands. BACKGROUND: Between 2011 and 2015, the use of MIG increased from 4%
      to 53% in the Netherlands. METHODS: This population-based cohort study included
      all patients with curable gastric adenocarcinoma that underwent gastrectomy
      between 2011 and 2015, registered in the Dutch Upper GI Cancer Audit. Patients
      with missing preoperative data, and patients in whom no lymphadenectomy or
      reconstruction was performed were excluded. Propensity score matching was applied
      to create comparable groups between patients receiving MIG or OG, using year of
      surgery and other potential confounders. Morbidity, mortality, and hospital stay
      were evaluated. RESULTS: Of the 1697 eligible patients, 813 were discarded after
      propensity score matching; 442 and 442 patients who underwent MIG and OG,
      respectively, remained. Conversions occurred in 10% of the patients during MIG.
      Although the overall postoperative morbidity (37% vs 40%, P = 0.489) and
      mortality rates (6% vs 4%, P = 0.214) were comparable between the 2 groups,
      patients who underwent MIG experienced less wound complications (2% vs 5%, P =
      0.006). Anastomotic leakage occurred in 8% of the patients after MIG, and in 7%
      after OG (P = 0.525). The median hospital stay declined over the years for both
      procedures (11 to 8 days, P < 0.001). Overall, hospital stay was shorter after
      MIG compared with OG (8 vs 10 days, P < 0.001). CONCLUSIONS: MIG was safely
      introduced in the Netherlands, with overall morbidity and mortality comparable
      with OG, less wound complications and shorter hospitalization.

PMID- 28742709
TI  - Prospective Evaluation of Precision Multimodal Gallbladder Surgery Navigation:
      Virtual Reality, Near-infrared Fluorescence, and X-ray-based Intraoperative
      Cholangiography.
AB  - OBJECTIVE: We aimed to prospectively evaluate NIR-C, VR-AR, and x-ray
      intraoperative cholangiography (IOC) during robotic cholecystectomy. BACKGROUND:
      Near-infrared cholangiography (NIR-C) provides real-time, radiation-free biliary
      anatomy enhancement. Three-dimensional virtual reality (VR) biliary anatomy
      models can be obtained via software manipulation of magnetic resonance
      cholangiopancreatography, enabling preoperative VR exploration, and
      intraoperative augmented reality (AR) navigation. METHODS: Fifty-eight patients
      were scheduled for cholecystectomy for gallbladder lithiasis. VR surgical
      planning was performed on virtual models. At anesthesia induction, indocyanine
      green was injected intravenously. AR navigation was obtained by overlaying the
      virtual model onto real-time images. Before and after Calot triangle dissection,
      NIR-C was obtained by turning the camera to NIR mode. Finally, an IOC was
      performed. The 3 modality performances were evaluated and image quality was
      assessed with a Likert-scale questionnaire. RESULTS: The three-dimensional VR
      planning enabled the identification of 12 anatomical variants in 8 patients, of
      which only 7 were correctly reported by the radiologists (P = 0.037). A dangerous
      variant identified at VR induced a "fundus first" approach. The cystic-common
      bile duct junction was visualized before Calot triangle dissection at VR in 100%
      of cases, at NIR-C in 98.15%, and in 96.15% at IOC.Mean time to obtain relevant
      images was shorter with NIR-C versus AR (P = 0.008) and versus IOC (P =
      0.00000003). Image quality scores were lower with NIR-C versus AR (P = 0.018) and
      versus IOC (P < 0.0001). CONCLUSIONS: This high-tech protocol illustrates the
      multimodal imaging of biliary anatomy towards precision cholecystectomy. Those
      visualization techniques could complement to reduce the likelihood of biliary
      injuries (NCT01881399).

PMID- 28742710
TI  - Using Confidential Clinical Data Registries for Public Reporting and Pay for
      Performance.

PMID- 28742711
TI  - Readiness of US General Surgery Residents for Independent Practice.
AB  - OBJECTIVE: This study evaluates the current state of the General Surgery (GS)
      residency training model by investigating resident operative performance and
      autonomy. BACKGROUND: The American Board of Surgery has designated 132 procedures
      as being "Core" to the practice of GS. GS residents are expected to be able to
      safely and independently perform those procedures by the time they graduate.
      There is growing concern that not all residents achieve that standard. Lack of
      operative autonomy may play a role. METHODS: Attendings in 14 General Surgery
      programs were trained to use a) the 5-level System for Improving and Measuring
      Procedural Learning (SIMPL) Performance scale to assess resident readiness for
      independent practice and b) the 4-level Zwisch scale to assess the level of
      guidance (ie, autonomy) they provided to residents during specific procedures.
      Ratings were collected immediately after cases that involved a categorical GS
      resident. Data were analyzed using descriptive statistics and supplemented with
      Bayesian ordinal model-based estimation. RESULTS: A total of 444 attending
      surgeons rated 536 categorical residents after 10,130 procedures. Performance:
      from the first to the last year of training, the proportion of Performance
      ratings for Core procedures (n = 6931) at "Practice Ready" or above increased
      from 12.3% to 77.1%. The predicted probability that a typical trainee would be
      rated as Competent after performing an average Core procedure on an average
      complexity patient during the last week of residency training is 90.5% (95% CI:
      85.7%-94%). This falls to 84.6% for more complex patients and to less than 80%
      for more difficult Core procedures. Autonomy: for all procedures, the proportion
      of Zwisch ratings indicating meaningful autonomy ("Passive Help" or "Supervision
      Only") increased from 15.1% to 65.7% from the first to the last year of training.
      For the Core procedures performed by residents in their final 6 months of
      training (cholecystectomy, inguinal/femoral hernia repair, appendectomy, ventral
      hernia repair, and partial colectomy), the proportion of Zwisch ratings (n = 357)
      indicating near-independence ("Supervision Only") was 33.3%. CONCLUSIONS: US
      General Surgery residents are not universally ready to independently perform Core
      procedures by the time they complete residency training. Progressive resident
      autonomy is also limited. It is unknown if the amount of autonomy residents do
      achieve is sufficient to ensure readiness for the entire spectrum of independent
      practice.

PMID- 28742712
TI  - Specialist Physicians' Attitudes and Practice Patterns Regarding Disclosure of
      Pre-referral Medical Errors.
AB  - OBJECTIVE: Our objective was to determine specialist physicians' attitudes and
      practices regarding disclosure of pre-referral errors. SUMMARY BACKGROUND DATA:
      Physicians are encouraged to disclose their own errors to patients. However, no
      clear professional norms exist regarding disclosure when physicians discover
      errors in diagnosis or treatment that occurred at other institutions before
      referral. METHODS: We conducted semistructured interviews of cancer specialists
      from 2 National Cancer Institute-designated Cancer Centers. We purposively
      sampled specialists by discipline, sex, and experience-level who self-described a
      >50% reliance on external referrals (n = 30). Thematic analysis of verbatim
      interview transcripts was performed to determine physician attitudes regarding
      disclosure of pre-referral medical errors; whether and how physicians disclose
      these errors; and barriers to providing full disclosure. RESULTS: Participants
      described their experiences identifying different types of pre-referral errors
      including errors of diagnosis, staging and treatment resulting in adverse events
      ranging from decreased quality of life to premature death. The majority of
      specialists expressed the belief that disclosure provided no benefit to patients,
      and might unnecessarily add to their anxiety about their diagnoses or prognoses.
      Specialists had varying practices of disclosure including none, non-verbal,
      partial, event-dependent, and full disclosure. They identified a number of
      barriers to disclosure, including medicolegal implications and damage to referral
      relationships, the profession's reputation, and to patient-physician
      relationships. CONCLUSIONS: Specialist physicians identify pre-referral errors
      but struggle with whether and how to provide disclosure, even when clinical
      circumstances force disclosure. Education- or communication-based interventions
      that overcome barriers to disclosing pre-referral errors warrant development.

PMID- 28742713
TI  - Does Prolonged Enteral Feeding With Supplemental Omega-3 Fatty Acids Impact on
      Recovery Post-esophagectomy: Results of a Randomized Double-Blind Trial.
AB  - OBJECTIVE: This randomized controlled trial (RCT) hypothesized that prolonged
      enteral nutrition (EN) with supplemental eicosapentanoic acid (EPA), an omega-3
      fatty acid with immune and anabolic properties, may impact on clinical and
      nutritional outcomes. BACKGROUND: Esophagectomy is associated with significant
      weight loss and catabolism, and negatively impacts quality of life (QL).
      Strategies to counter sustained catabolism have therapeutic rationale. METHODS:
      This multicenter, double-blind, placebo-controlled RCT was powered on a 5%
      difference in lean body mass (LBM) at 1 month. Patients were randomly assigned to
      receive either EN-EPA (2.2 g EPA/day) (n = 97) or isocaloric isonitrogenous
      standard EN (EN-S) (n = 94), preoperatively (5 days orally), and postoperatively
      via a jejunostomy until 1 month postdischarge. Assessments perioperatively, and
      at 1, 3, and 6 months included weight, body mass index (BMI), body composition,
      muscle strength, cytokines, complications, and QL. RESULTS: The median (range)
      nutrition support was for 51 (36 to 78) days, and overall compliance was 96%. For
      the entire cohort, a significant (P < 0.005) decrease in weight (-7.4 +/- 6.6
      kg), BMI (-2.6 +/- 2.2 kg/m), LBM (-2.5 +/- 8.7 kg), and fat mass (-3.4 +/- 5.8
      kg) was evident from preoperatively to 6 months. The mean (+/-SD) loss of LBM
      (kg) at 1 month was -3.7 +/- 8.7 in the EN-S group, compared with -5.6 +/- 12.1
      in the EN-EPA group (P = 0.355). Per-protocol analysis revealed no difference
      between the EN-EPA and EN-S in any clinical, nutritional, functional, QL or
      immune parameter at any time point. CONCLUSIONS: The thesis that EPA impacts on
      anabolism, immune function, and clinical outcomes post-esophagectomy was not
      supported. Compliance with home EN was excellent, but weight, muscle, and fat
      loss was significant in 30% of patients, highlighting the complexity of
      postoperative weight loss.

PMID- 28742714
TI  - Impact of Extracapsular Lymph Node Involvement After Neoadjuvant Chemoradiation
      Therapy Followed by Surgery in Carcinoma of the Esophagus: A Multicenter Study.
AB  - OBJECTIVES: The current study aims to examine the impact of extracapsular lymph
      node involvement (EC-LNI) on survival for both esophageal adenocarcinoma (AC) and
      squamous cell carcinoma (SCC) treated with neoadjuvant chemoradiation therapy
      (nCRT) followed by surgery. BACKGROUND: Studies have demonstrated the negative
      prognostic value of EC-LNI in primary surgery, but its impact after nCRT remains
      unclear. METHODS: From the databases of 6 European high-volume centers 1505
      patients with R0 resections were withheld. Oncologic variables, including ypT,
      ypN, number of positive lymph nodes, and lymph node capsular status: EC-LNI and
      intracapsular lymph node involvement (IC-LNI), were examined. Statistical
      analysis was performed by Cox proportional hazards modeling. RESULTS: In SCC 182
      patients (31.6%) had positive lymph nodes, of whom 60 (33.0%) showed EC-LNI. In
      AC 391 patients (42.1%) had positive lymph nodes, of whom 147 (37.6%) showed EC
      LNI. Overall 5-year survival (O5YS) in SCC was 42.0%. Presence of EC-LNI meant a
      significantly worse O5YS than IC-LNI or pN0 (10.6%, 39.5%, and 47.4%,
      respectively; P < 0.05). O5YS in AC was 41.2%. No significant difference was
      observed between EC-LNI and IC-LNI (P = 0.322). In the multivariate analysis,
      among the examined possible prognosticators, presence of EC-LNI showed the
      highest hazard ratio (2.29, confidence interval: 1.52-3.47) as an independent
      prognosticator for overall survival in SCC, but it was not in AC. CONCLUSIONS:
      Based on this international multicenter study, the presence of EC-LNI after nCRT
      is at least as important as N-stage for survival and EC-LNI is the strongest
      prognosticator for overall survival in SCC but not in AC.

PMID- 28742715
TI  - Limb-Salvage Options in Growing Children with Malignant Bone Tumors of the Lower
      Extremity: A Critical Analysis Review.

PMID- 28742716
TI  - Management of Scoliosis in Children with Osteogenesis Imperfecta.

PMID- 28742717
TI  - Integrating an Interprofessional Education Experience Into a Human Physiology
      Course.
AB  - PURPOSE: To obtain physician assistant (PA) student perceptions about an
      interprofessional education (IPE) training experience embedded in a
      multidisciplinary science course. METHODS: An IPE training experience was
      integrated into a graduate human physiology course offered to PA, physical
      therapy, and graduate studies students. The focus of the activity related to the
      Interprofessional Education Collaborative (IPEC) competency domains of (1) roles
      and responsibilities and (2) teams and teamwork. Effectiveness was assessed in
      pretraining and posttraining surveys, which included questions addressing student
      self-perceptions of IPEC competency domains, student assessment of the learning
      activity, and student reflection. RESULTS: We observed a statistically
      significant positive change in PA student perceptions of IPEC competency domains.
      Students also provided a positive evaluation of the IPE activity and communicated
      personal improvements in IPE perspectives. CONCLUSIONS: Incorporating planned IPE
      experiences into multidisciplinary health science courses represents an
      appropriate venue for PA students to learn and apply interprofessional
      competencies, which may benefit future interprofessional practice.

PMID- 28742718
TI  - Similar Findings Regarding Predictors of PANCE Performance.

PMID- 28742719
TI  - Pediatric Gastroenterologists' Approach to Venous Thromboembolism Prophylaxis in
      Pediatric Inflammatory Bowel Disease.
AB  - The risk of venous thromboembolism (VTE) is significantly increased in patients
      with inflammatory bowel disease (IBD). For the adult population, prophylaxis
      guidelines exist to help guide physicians in their management of high-risk IBD
      patients. Although it is known that children with IBD also experience increased
      rates of VTE, there is no clear consensus on how best to prevent these unwanted
      complications. We sought to better understand practicing pediatric
      gastroenterologists' awareness of this issue and practices surrounding prevention
      of VTE in their pediatric patients. We found that pediatric gastroenterologists
      are well aware of the increased risk for VTE in children with IBD, that
      anticoagulant prophylaxis is infrequently used for pediatric patients, and that
      the most commonly cited reason for not providing prophylaxis is the lack of
      available guidelines in the literature.

PMID- 28742720
TI  - Cholangioscopic Management of Mirizzi Syndrome in a Pediatric Patient.

PMID- 28742721
TI  - Hepatic Portocholecystostomy: 97 Cases From a Single Institution.
AB  - OBJECTIVES: Approximately 20% of cases of biliary atresia do not involve the
      gallbladder, the cystic duct, and the common bile duct. In these cases, a
      hepatoportocholecystostomy (HPC) may be performed instead of the classical
      hepatoportoenterostomy (HPE). METHODS: We reviewed our cohort to investigate the
      efficacy of HPC and the associated surgical complications and clinical problems.
      RESULTS: From 1984 to 2009, 97 patients underwent HPC in our institution. In the
      first 6 months of the postoperative period no patient presented with bacterial
      cholangitis. Nine patients had bile leakage, and 1 patient had a gallbladder
      obstruction. For these 10 patients, HPC was modified in HPE. Jaundice clearance
      was maintained after HPE, but 4 of the patients presented 1 or more cholangitis
      episodes. After 6 months, there were no cases of cholangitis recorded, 2 patients
      presented bile leakage and 4 patients experienced gallbladder obstruction. After
      5 years of follow-up, 46% of the patients were jaundice free with their native
      liver and 29.4% were transplanted. CONCLUSIONS: In patients with biliary atresia
      with patent extrahepatic bile ducts, hepatoportocholecystomy is a good surgical
      technique that can prevent cholangitis. These results are counterbalanced by
      specific surgical complications that need to be known and looked for in the
      postoperative period.

PMID- 28742722
TI  - Attention Deficit Hyperactivity Disorder and Functional Defecation Disorders in
      Children.
AB  - OBJECTIVES: The aim of the study was to assess the prevalence of attention
      deficit hyperactivity disorder (ADHD) in children presenting with functional
      defecation disorders (FDDs) and to assess the prevalence of FDDs in children with
      ADHD. METHODS: A cross-sectional cohort study was carried out between September
      2014 and May 2016. Group 1: Parents of children with FDDs according to the Rome
      III criteria completed the Child Behavior Checklist and the VvGK (Dutch
      questionnaire based on the American Disruptive Behavior Disorder rating scale).
      Patients with ADHD subarea scores >=70 on the Child Behavior Checklist and/or
      >=16 on the VvGK were referred for further psychiatric evaluation. Group 2:
      Parents of children treated for ADHD at a specialized ADHD outpatient clinic
      completed a standardized questionnaire regarding their child's defecation
      pattern. RESULTS: In group 1 (282 children with FDDs), 10.3% (7.1%-13.5% bias
      corrected and accelerate confidence interval) were diagnosed with ADHD. Group 2
      consisted of 198 children with ADHD, 22.7% (17.6-28.8 bias-corrected and
      accelerate confidence interval) fulfilled the Rome III criteria for an FDD.
      Children with both an FDD and ADHD reported urinary incontinence significantly
      more often compared to children with an FDD or ADHD alone: 57.1% in FDD + ADHD
      versus 22.8% in FDD alone (P < 0.001) and 31.1% in ADHD + FDD versus 7.8% in ADHD
      alone (P < 0.001). CONCLUSIONS: Approximately 10.3% of children with FDDs had
      ADHD and 22.7% of children with a known diagnosis of ADHD fulfilled the Rome III
      criteria for an FDD. This observation suggests that screening for behavioral
      disorders and FDDs should be incorporated into the diagnostic workup of these
      groups of children.

PMID- 28742723
TI  - Supraglottic Atomization of Surfactant in Spontaneously Breathing Lambs Receiving
      Continuous Positive Airway Pressure.
AB  - OBJECTIVES: To determine the short-term tolerance, efficacy, and lung deposition
      of supraglottic atomized surfactant in spontaneously breathing lambs receiving
      continuous positive airway pressure. DESIGN: Prospective, randomized animal
      study. SETTING: Animal research laboratory. SUBJECTS: Twenty-two preterm lambs on
      continuous positive airway pressure (132 +/- 1 d gestational age). INTERVENTIONS:
      Animals receiving continuous positive airway pressure via binasal prongs at 8 cm
      H2O were randomized to receive atomized surfactant at approximately 60-minute of
      life (atom; n = 15) or not (control; n = 7). The atom group received 200 mg/kg of
      poractant alfa (Curosurf; Chiesi Farmaceutici SpA, Parma, Italy) over 45 minutes
      via a novel atomizer located in the upper pharynx that synchronized surfactant
      delivery with the inspiratory phase. MEASUREMENTS AND MAIN RESULTS: Arterial
      blood gas, regional distribution of tidal ventilation (electrical impedance
      tomography), and carotid blood flow were recorded every 15 minutes until 90
      minutes after stabilizing on continuous positive airway pressure. Gas exchange,
      respiratory rate, and hemodynamic variables, including carotid blood flow,
      remained stable during surfactant treatment. There was a significant improvement
      in arterial alveolar ratio after surfactant delivery in the atom group (p < 0.05;
      Sidak posttests), while there was no difference in PaCO2. Electrical impedance
      tomography data showed a more uniform pattern of ventilation in the atom group.
      In the atom group, the median (interquartile range) deposition of surfactant in
      the lung was 32% (22-43%) of the delivered dose, with an even distribution
      between the right and the left lungs. CONCLUSIONS: In our model of spontaneously
      breathing lambs receiving CPAP, supraglottic atomization of Curosurf via a novel
      device was safe, improved oxygenation and ventilation homogeneity compared with
      CPAP only, and provided a relatively large lung deposition suggesting clinical
      utility.

PMID- 28742725
TI  - Antiphospholipid Syndrome: It's Far More Than You Think.

PMID- 28742726
TI  - CREST Syndrome: Clinical Expression of the Disease.

PMID- 28742724
TI  - Epidemiology of Noninvasive Ventilation in Pediatric Cardiac ICUs.
AB  - OBJECTIVE: To describe the epidemiology of noninvasive ventilation therapy for
      patients admitted to pediatric cardiac ICUs and to assess practice variation
      across hospitals. DESIGN: Retrospective cohort study using prospectively
      collected clinical registry data. SETTING: Pediatric Cardiac Critical Care
      Consortium clinical registry. PATIENTS: Patients admitted to cardiac ICUs at PC4
      hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed all
      cardiac ICU encounters that included any respiratory support from October 2013 to
      December 2015. Noninvasive ventilation therapy included high flow nasal cannula
      and positive airway pressure support. We compared patient and, when relevant,
      perioperative characteristics of those receiving noninvasive ventilation to all
      others. Subgroup analysis was performed on neonates and infants undergoing major
      cardiovascular surgery. To examine duration of respiratory support, we created a
      casemix-adjustment model and calculated adjusted mean durations of total
      respiratory support (mechanical ventilation + noninvasive ventilation),
      mechanical ventilation, and noninvasive ventilation. We compared adjusted
      duration of support across hospitals. The cohort included 8,940 encounters from
      15 hospitals: 3,950 (44%) received noninvasive ventilation and 72% were neonates
      and infants. Medical encounters were more likely to include noninvasive
      ventilation than surgical. In surgical neonates and infants, 2,032 (55%) received
      postoperative noninvasive ventilation. Neonates, extracardiac anomalies, single
      ventricle, procedure complexity, preoperative respiratory support, mechanical
      ventilation duration, and postoperative disease severity were associated with
      noninvasive ventilation therapy (p < 0.001 for all). Across hospitals,
      noninvasive ventilation use ranged from 32% to 65%, and adjusted mean noninvasive
      ventilation duration ranged from 1 to 4 days (3-d observed mean). Duration of
      total adjusted respiratory support was more strongly correlated with duration of
      mechanical ventilation compared with noninvasive ventilation (Pearson r = 0.93 vs
      0.71, respectively). CONCLUSIONS: Noninvasive ventilation use is common in
      cardiac ICUs, especially in patients admitted for medical conditions, infants,
      and those undergoing high complexity surgery. We observed wide variation in
      noninvasive ventilation use across hospitals, though the primary driver of total
      respiratory support time seems to be duration of mechanical ventilation.

PMID- 28742727
TI  - Cryopyrin Cry.

PMID- 28742728
TI  - Anti-N-Methyl-D-Aspartate-Receptor Encephalitis Complicated With Antiphospholipid
      Syndrome and Cerebral Venous Thrombosis.

PMID- 28742729
TI  - Pericardial Effusion: A Rare Side Effect of TNF-Alpha Blocking Agent.

PMID- 28742730
TI  - Predictive Model for Neoplastic Potential of Gallbladder Polyp.
AB  - GOAL: To provide the statistical predictive model for neoplastic potential of
      gallbladder polyp (GBP). BACKGROUND: Many studies have attempted to define the
      risk factors for neoplastic potential of GBP. It remains difficult to precisely
      adapt the reported risk factors for the decision of surgery. Estimating the
      probability for neoplastic potential of GBP using a combination of several risk
      factors before surgical resection would be useful in patient consultation. STUDY:
      We collected data of patients confirmed as GBP through cholecystectomy at Samsung
      Medical Center between January 1997 and March 2015. Those with a definite
      evidence for malignancy, such as adjacent organ invasion, metastasis on
      preoperative imaging studies, polyp >15 mm, and absence of proper preoperative
      ultrasonographic imaging were excluded. A total of 1976 patients were enrolled.
      To make and validate the predictive model, we divided the cohort into the
      modeling group (n=979) and validation group (n=997). Clinical information,
      ultrasonographic findings, and blood tests were retrospectively analyzed.
      RESULTS: Clinical factors of older age, single lesion, sessile shape, and polyp
      size showed statistical significance for neoplastic potential of GBP in the
      modeling group. A predictive model for neoplastic potential of GBP was
      constructed utilizing the statistical outcome of the modeling group. Statistical
      validation was performed with the validation group to determine the optimal
      clinical sensitivity and specificity of the predictive model. Optimal cut-off
      value for neoplastic probability was 7.4%. CONCLUSIONS: The predictive model for
      neoplastic potential of GBP may support clinical decisions before
      cholecystectomy.

PMID- 28742731
TI  - Endoscopic Ultrasound-guided Portal Venous Access: Diagnostic and Therapeutic
      Implications.
AB  - Endoscopic ultrasound (EUS) has evolved from a purely diagnostic to an
      interventional modality offering minimally invasive alternatives to surgical and
      radiologic interventions. This has led to a rapidly growing interest in EUS
      guided vascular interventions. EUS-guided portal venous access is an emerging
      technique which opens a new arena for interventional vascular EUS. Portal vein
      can be accessed under EUS guidance with high precision and low risk of
      complications thus expanding its application for both benign and malignant
      conditions. Potential applications of EUS-guided portal vein access include: fine
      needle aspiration of portal vein thrombus and portal venous blood sampling for
      circulating tumor cells for diagnosis and staging of occult and known
      malignancies; portal vein angiography, portal pressure measurement, and creation
      of endoscopic intrahepatic portosystemic shunt; portal vein embolization and
      targeted drug delivery. This article will review the current literature on EUS
      guided portal vein access, its feasibility and safety in animal and human
      studies, and current diagnostic and therapeutic applications with future
      directions.

PMID- 28742732
TI  - Educational Colonoscopy Video Enhances Bowel Preparation Quality and
      Comprehension in an Inner City Population.
AB  - BACKGROUND: Quality of bowel preparation and patient knowledge remains a major
      barrier for completing colorectal cancer screening. Few studies have tested
      unique ways to impact patient understanding centering on interactive computer
      programs, pictures, and brochures. Two studies explored instructional videos but
      focused on patient compliance and anxiety as endpoints. Furthermore, excessive
      video length and content may limit their impact on a broad patient population. No
      study so far has studied a video's impact on preparation quality and patient
      understanding of the colonoscopy procedure. METHODS: We conducted a single
      blinded prospective study of inner city patients presenting for a first time
      screening colonoscopy. During their initial visit patients were randomized to
      watch an instructional colonoscopy video or a video discussing gastroesophageal
      reflux disease (GERD). All patients watched a 6 minutes long video with the same
      spokesperson, completed a demographic questionnaire (Supplemental Digital Content
      1, http://links.lww.com/JCG/A352) and were enrolled only if screened within 30
      days of their visit. On the day of the colonoscopy, patients completed a 14
      question quiz of their knowledge. Blinded endoscopist graded patient preparations
      based on the Ottawa scale. All authors had access to the study data and reviewed
      and approved the final manuscript. RESULTS: Among the 104 subjects enrolled in
      the study, 56 were in the colonoscopy video group, 48 were in GERD video group,
      and 12 were excluded. Overall, 48% were male and 52% female; 90% of patients had
      less than a high school education, 76% were African American, and 67% used a 4 L
      split-dose preparation. There were no differences between either video group with
      regard to any of the above categories. Comparisons between the 2 groups revealed
      that the colonoscopy video group had significantly better Ottawa bowel
      preparation score (4.77 vs. 6.85; P=0.01) than the GERD video group. The
      colonoscopy video group also had less-inadequate repeat bowel preparations versus
      the GERD video group (9% vs. 23%; P<0.01). The overall score on the knowledge
      questionnaire (Supplemental Digital Content 1, http://links.lww.com/JCG/A352) was
      significantly higher in the colonoscopy video group as compared with the GERD
      video group (12.77 vs. 11.08; P<0.001. In all patients the overall quiz score
      positively correlated with preparation quality (odds ratio, 2.31; confidence
      interval, 1.35-3.94; P<0.001). CONCLUSIONS: Our unique population represented an
      overwhelmingly under-educated (85% had a high school education or less) and
      minority group (76% African American). They are one of the most at risk of having
      multiple barriers such as comprehension and reading difficulties resulting in
      poor preparation examinations and no shows to procedures. Our instructional video
      proved to be high yield in this population. The patients assigned to watch the
      colonoscopy video showed a significant increase in "excellent" grade adequate
      bowel preparation quality by >23% and a significant decrease in "inadequate"
      bowel preparations by almost 50%. Our study proves that an educational video can
      improve both comprehension with regard to all aspects of colonoscopy.
      ClinicalTrials.gov number, NCT02906969.

PMID- 28742733
TI  - Intravoxel Incoherent Motion: Model-Free Determination of Tissue Type in
      Abdominal Organs Using Machine Learning.
AB  - PURPOSE: For diffusion data sets including low and high b-values, the intravoxel
      incoherent motion model is commonly applied to characterize tissue. The aim of
      the present study was to show that machine learning allows a model-free approach
      to determine tissue type without a priori assumptions on the underlying
      physiology. MATERIALS AND METHODS: In 8 healthy volunteers, diffusion data sets
      were acquired using an echo-planar imaging sequence with 16 b-values in the range
      between 0 and 1000 s/mm. Using the k-nearest neighbors technique, the machine
      learning algorithm was trained to distinguish abdominal organs (liver, kidney,
      spleen, muscle) using the signal intensities at different b-values as training
      features. For systematic variation of model complexity (number of neighbors),
      performance was assessed by calculation of the accuracy and the kappa coefficient
      (kappa). Most important b-values for tissue discrimination were determined by
      principal component analysis. RESULTS: The optimal trade-off between model
      complexity and overfitting was found in the range between K = 11 to 13. On "real
      world" data not previously applied to optimize the algorithm, the k-nearest
      neighbors algorithm was capable to accurately distinguish tissue types with best
      accuracy of 94.5% and kappa = 0.92 reached for intermediate model complexity (K =
      11). The principal component analysis showed that most important b-values are
      (with decreasing importance): b = 1000 s/mm, b = 970 s/mm, b = 750 s/mm, b = 20
      s/mm, b = 620 s/mm, and b = 40 s/mm. Applying a reduced set of 6 most important b
      values, still a similar accuracy was achieved on the real-world data set with an
      average accuracy of 93.7% and a kappa coefficient of 0.91. CONCLUSIONS: Machine
      learning allows for a model-free determination of tissue type using intra voxel
      incoherent motion signal decay curves as features. The technique may be useful
      for segmentation of abdominal organs or distinction between healthy and
      pathological tissues.

PMID- 28742734
TI  - Evaluation of Gadolinium Retention After Serial Administrations of a Macrocyclic
      Gadolinium-Based Contrast Agent (Gadobutrol): A Single-Institution Experience
      With 189 Patients.
AB  - OBJECTIVE: There has been controversy as to whether gadobutrol, one of the widely
      used macrocyclic gadolinium-based contrast agents, can lead to gadolinium
      retention after serial injections. Our aim was to validate whether serial
      administrations of gadobutrol can cause signal increase in the dentate nucleus
      (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance (MR)
      images due to gadolinium retention. MATERIALS AND METHODS: A total of 189
      patients who had undergone at least 2 contrast-enhanced MR scans using only
      gadobutrol between August 2009 and August 2016 were retrospectively included. The
      DN-to-pons and GP-to-thalamus signal intensity (SI) ratio differences on
      unenhanced T1-weighted MR images were calculated by subtracting the SI ratios at
      the first MR images from those at the last MR images. One-sample t tests were
      used to evaluate whether the SI ratio differences differed from 0. Linear
      regression and Pearson correlations were performed to assess correlations between
      SI ratio differences and various confounding variables, including the number of
      MR scans, mean time interval between MR scans, age, sex, history of radiation
      therapy or chemotherapy, and renal and liver functions. RESULTS: Patients
      underwent a mean of 5.9 +/- 6.3 contrast-enhanced MR scans with a mean interval
      of 42.8 +/- 49.5 weeks between the scans. Sixty-three patients underwent 6 or
      more MR scans, whereas 126 patients underwent fewer than 6 MR scans. Neither the
      DN-to-pons SI nor the GP-to-thalamus SI ratio differences differed significantly
      from 0, with mean values of -0.012 +/- 0.115 (P = 0.148) and 0.012 +/- 0.111 (P =
      0.126), respectively. CONCLUSIONS: Serial administrations of gadobutrol did not
      result in signal increases in the DN or GP on unenhanced T1-weighted MR images
      due to gadolinium retention.

PMID- 28742736
TI  - Comparative Analysis of Perioperative Outcomes Using Nationally Derived Hospital
      Discharge Data Relative to a Prospective Multicenter Surgical Database of Adult
      Spinal Deformity Surgery.
AB  - STUDY DESIGN: Retrospective analysis of three prospectively collected databases.
      OBJECTIVE: To compare perioperative outcomes in Adult Spinal Deformity (ASD)
      surgeries in a surgeon-run (SR-ASD) and two national databases: the Nationwide
      Inpatient Sample (NIS) and the National Surgical Quality Improvement Program
      (NSQIP). SUMMARY OF BACKGROUND DATA: Much has been learned on the treatment of
      ASD in the last decade with prospective multicenter collaborative research
      focusing on this specific condition. Nondisease specific national databases are
      being used for hypothesis and quality control testing on a large number of ASD
      patients. Their accuracy and applicability remains unevaluated. METHODS: Patients
      were identified on each respective database undergoing lumbar spine fusion for
      ASD. Propensity score matching established cohorts of patients on each database
      with similar procedures being performed. Complication prevalence and relative
      risk was compared on the NIS and NSQIP against SR-ASD. Secondary outcome measures
      included hospital-stay characteristics, surgical invasiveness, patient
      demographics, and patient comorbidities. RESULTS: Two hundred fifty-five patients
      were identified on each database 1:1:1 with similar overall surgical intensity.
      Querying the databases using ICD-9 codes, CPT codes, and surgeon-reports resulted
      in different complication incidences: overall complication rates were 17.65% on
      NIS, 24.31% on NSQIP, and 68.24% on SR-ASD. The relative risk of a medical
      complication in SR-ASD was 1.87 (1.42-2.48) relative to NIS and 1.91 (1.44-2.54)
      relative to NSQIP. The relative risk of a surgical complication was 5.45 (2.69
      11.05) compared with NIS and 12.05 (3.98-36.49) compared with NSQIP. CONCLUSION:
      After selecting patients using the same criteria and diagnosis, NIS, NSQIP, and
      SR-ASD databases captured different patient populations and different
      complication incidences. There were total absences of certain complications
      contrary to usual literature rates in all three databases. Faithful reporting
      necessitates understanding database limitations, and careful evaluation of
      database strengths and weaknesses is paramount to accurate reports. LEVEL OF
      EVIDENCE: 3.

PMID- 28742737
TI  - The Azygos Vein Is at Potential Risk of Injury From Malpositioning of Left
      Thoracic Pedicle Screw in Thoracic Adolescent Idiopathic Scoliosis Patients.
AB  - STUDY DESIGN: A computed tomography study. OBJECTIVE: To evaluate the changed
      position of azygos vein in patients with thoracic adolescent idiopathic scoliosis
      (AIS) and to analyze the potential risk of injury of azygos vein from thoracic
      pedicle screw placement in these patients. SUMMARY OF BACKGROUND DATA: It has
      been widely recognized that the anatomic positions of structures adjacent to the
      vertebrae may change in patients with AIS. To date, no study had evaluated such
      change of azygos vein in patients with AIS. METHODS: Twenty-five patients with
      thoracic AIS and 17 age-matched normal teenagers were included in the present
      study. Axial computed tomography images from T7 to T10 level were obtained to
      evaluate azygos vein-vertebral angle (defined as 0 degrees  when the azygos vein
      was located directly laterally to the left and 180 degrees  when directly
      laterally to the right). The percentage of azygos vein located in the direction
      of left screw passage was calculated to analyze the potential risk of injury from
      left pedicle screw placement. RESULTS: The azygos vein-vertebral angles were
      significantly smaller in patients with AIS when compared with normal teenagers
      from T7 to T10 level (P < 0.001). The percentage of azygos vein at high risk of
      injury from left pedicle screw placement was 80% (20/25) at T7 level, 84% (21/25)
      at T8 level, 76% (19/25) at T9 level, and 72% (18/25) at T10 level in patients
      with AIS. No azygos vein was found to be at risk of injury from right pedicle
      screw placement in patients with AIS. The azygos vein was safe from pedicle screw
      placement on both sides in normal teenagers. CONCLUSION: The changed relative
      anatomic position of azygos vein in patients with thoracic AIS places the azygos
      vein at high potential risk of injury from excessively long left pedicle screw
      placement. Spine surgeons should choose appropriate screw length to avoid
      anterior cortex perforation. LEVEL OF EVIDENCE: 3.

PMID- 28742738
TI  - Necrotizing enterocolitis: Current concepts in practice.
AB  - Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in
      preterm infants and continues to be a major cause of morbidity and mortality. The
      incidence of NEC as well as mortality from the disease has persisted at
      unacceptably high levels for decades as current understanding of the cause
      remains incomplete. Identifying infants at risk and preventing NEC are mainstays
      of care. This article briefly examines disease presentation and treatment,
      identifies gaps in current understanding of disease pathology, and highlights new
      research that may lead to a decrease in the incidence of NEC in the future.

PMID- 28742740
TI  - Penetrating aortic ulcer leading to aortic dissection.
AB  - Rarely, penetrating atherosclerotic ulcers can rupture into the wall of the
      aorta, resulting in acute aortic dissection. This article describes a woman with
      an incidental diagnosis of type A aortic dissection secondary to a penetrating
      atherosclerotic ulcer of the ascending aorta. Although surgical repair of the
      aortic root was recommended, the patient refused treatment and left against
      medical advice.

PMID- 28742741
TI  - An unusual case of acute parotitis in a young adult.
AB  - Acute bacterial parotitis is uncommon in young adults. Infection with Serratia
      marcescens is even rarer and usually found in hospitalized patients. This case
      report focuses on a young woman with acute bacterial parotitis caused by S.
      marcescens that required a longer-than-normal course of antibiotics.

PMID- 28742742
TI  - Practical applications of physical activity for successful cognitive aging.
AB  - As patients lose cognitive function, they lose autonomy and increasingly use
      fiscal, social, and medical resources. Healthcare costs for Americans older than
      age 65 years are three to five times higher than for the remaining population,
      and dementia is the third most costly disease in the United States. Interventions
      that promote successful aging can help patients and reduce the financial,
      workforce, and treatment resource burdens on the population. Because a
      relationship between physical activity, particularly aerobic exercise, and
      cognitive decline has been established, physical activity interventions may prove
      practical, affordable, and effective. Attention to empiric research and knowledge
      of evidence-based strategies for prescribing physical activity are critical for
      PAs to embrace.

PMID- 28742743
TI  - Expanding the role of PAs in the treatment of severe and persistent mental
      illness.
AB  - Patients with severe and persistent mental illness often face limited access to
      psychiatric and primary care. This exploratory qualitative analysis studied the
      effect of introducing a PA into a comprehensive outpatient psychiatric team.
      Early results suggest this model improves the quality and access to primary and
      psychiatric care.

PMID- 28742744
TI  - One PA's experiences in the Netherlands, South Africa, and Australia.
AB  - As the PA profession develops internationally, few mechanisms let PAs move from
      country to country for clinical practice opportunities. The first author of this
      paper has worked in the civilian health sectors in two countries, the Netherlands
      and South Africa, and taught PA students in South Africa and Australia. He
      reports on PA development in each country and reflects on and compares his
      professional and clinical experiences.

PMID- 28742745
TI  - From feldschers to physician assistants in Bulgaria.
AB  - The physician assistant (PA) profession was established in Bulgaria in 2014 in
      response to a growing shortage of medical staff and was modeled on the United
      States experience. Feldschers provided a similar role in Bulgaria from 1878 to
      1999 but feldscher training was discontinued in 1999 because of a physician
      surplus. However, healthcare in Bulgaria changed after the country joined the
      European Union, and some physicians left for better opportunities elsewhere. The
      loss of physicians and an aging population meant that PAs were seen as a strategy
      to offset Bulgaria's growing healthcare demand.

PMID- 28742746
TI  - Aortic regurgitation.

PMID- 28742747
TI  - A 50-year-old man with persistent hiccups.

PMID- 28742748
TI  - Beyond the PSA test: How to better stratify a patient's risk of prostate cancer.
AB  - The primary method of screening for and detecting prostate cancer is the prostate
      specific antigen (PSA) test. Although this test is very prostate-specific, it is
      not cancer-specific; conditions other than prostate cancer can cause an elevated
      PSA. Many efforts have been made to discover more specific tests and methods
      beyond the PSA. This article describes several literature-supported tests and
      methods to better stratify a man's risk of having prostate cancer.

PMID- 28742749
TI  - What is causing this man's worsening skin lesions?

PMID- 28742750
TI  - The big and the little.

PMID- 28742751
TI  - The business of oncology.

PMID- 28742754
TI  - MDs, DOs, and the physician-PA team.

PMID- 28742752
TI  - Best practices in PA development: Lessons from three countries.
AB  - As the PA profession moves into its 50th year and develops globally, its
      flexibility and underlying principles make it adaptable to a wide range of
      healthcare needs and governmental priorities. A key feature of effective PA
      development is adapting the profession to the needs of each country rather than
      adopting it exactly as it has developed in the United States. The successful
      adaptation of new PA models must assure that the new profession meets a societal
      need, such as increasing healthcare access for specific populations or geographic
      areas.

PMID- 28742755
TI  - The Lumbar Pelvic Angle, the Lumbar Component of the T1 Pelvic Angle, Correlates
      With HRQOL, PI-LL Mismatch, and it Predicts Global Alignment.
AB  - STUDY DESIGN: Prospective multicenter analysis of adult spinal deformity (ASD)
      patients. OBJECTIVE: The aim of this study was to introduce the lumbar pelvic
      angle (LPA), a novel parameter of spinopelvic alignment. SUMMARY OF BACKGROUND
      DATA: The T1 pelvic angle (TPA), a measure of global spinopelvic alignment,
      correlates with health-related quality of life (HRQOL), but it may not be
      measureable on all intraoperative x-rays. In patients with previous interbody
      fusion at L5-S1, the plane of the S1 endplate can be blurred, creating error in
      pelvic incidence and lumbar lordosis (PI-LL) measure. The LPA is more readily
      measured on intraoperative imaging than the TPA. METHODS: ASD patients were
      included with either coronal Cobb angle >20 degrees , sagittal vertical axis
      (SVA) >5 cm, thoracic kyphosis >60 degrees , or pelvic tilt (PT) >25 degrees .
      Measures of disability included Oswestry Disability Index (ODI), Scoliosis
      Research Society (SRS), and Short Form (SF)-36. Baseline and 2-year follow-up
      radiographic and HRQOL outcomes were evaluated. Linear regressions compared LPA
      with radiographic parameters and HRQOL. RESULTS: A total of 852 ASD patients (407
      operative) were enrolled (mean age 53.7). Baseline LPA correlated with PI-LL (r =
      0.79), PT (r = 0.78), TPA (r = 0.82), and SVA (r = 0.61) (all P < 0.001). PI-LL,
      LPA, and TPA correlated with ODI (r = 0.42/0.29/0.45), SF-36 physical component
      score (-0.43/-0.28/-0.45) SRS (-0.354/-0.23/-0.37) with all P < 0.001. At 2
      years' follow-up, LPA correlated with PI-LL (r = 0.77), PT (r = 0.78), TPA (r =
      0.83), and SVA (r = 0.57) (all P < 0.001). Categorizing patients by increasing
      LPA (<7 degrees ; 7 degrees -15 degrees ; >15 degrees ) revealed progressive
      increases in all HRQOL, PI-LL (-3.2 degrees /12.7 degrees /32.4 degrees ), and
      TPA (9.7 degrees /20.1 degrees /34.6 degrees ) with all P < 0.001. Moderate
      disability (ODI = 40) corresponded to LPA 10.1 degrees , PI-LL 12.6 degrees , and
      TPA 20.6 degrees . Mild disability (ODI = 20) corresponded to LPA 7.2 degrees ,
      PI-LL 4.2 degrees , and TPA 14.7 degrees . CONCLUSION: LPA correlates with TPA,
      PI-LL, and HRQOL in ASD patients. LPA can be used as an intraoperative tool to
      gauge correction with a target LPA of <7.2 degrees . LPA predicts global
      alignment, as it correlates with baseline and 2-year TPA and SVA. Along with the
      cervical-thoracic pelvic angle and TPA, LPA completes the fan of spinopelvic
      alignment. LEVEL OF EVIDENCE: 3.

PMID- 28742756
TI  - Cost-effectiveness of Mindfulness-based Stress Reduction Versus Cognitive
      Behavioral Therapy or Usual Care Among Adults With Chronic Low Back Pain.
AB  - STUDY DESIGN: Economic evaluation alongside a randomized trial of cognitive
      behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR) versus
      usual care alone (UC) for chronic low back pain (CLBP). OBJECTIVE: To determine 1
      year cost-effectiveness of CBT and MBSR compared to 33 UC. SUMMARY OF BACKGROUND
      DATA: CLBP is expensive in terms of healthcare costs and lost productivity. Mind
      body interventions have been found effective for back pain, but their cost
      effectiveness is unexplored. METHODS: A total of 342 adults in an integrated
      healthcare system with CLBP were randomized to receive MBSR (n = 116), CBT (n =
      113), or UC (n = 113). CBT and MBSR were offered in 8-weekly 2-hour group
      sessions. Cost-effectiveness from the societal perspective was calculated as the
      incremental sum of healthcare costs and productivity losses over change in
      quality-adjusted life-years (QALYs). The payer perspective only included
      healthcare costs. This economic evaluation was limited to the 301 health plan
      members enrolled >=180 days in the years pre-and postrandomization. RESULTS:
      Compared with UC, the mean incremental cost per participant to society of CBT was
      $125 (95% confidence interval, CI: -4103, 4307) and of MBSR was -$724 (CI: -4386,
      2778)-that is, a net saving of $724. Incremental costs per participant to the
      health plan were $495 for CBT over UC and -$982 for MBSR, and incremental back
      related costs per participant were $984 for CBT over UC and -$127 for MBSR. These
      costs (and cost savings) were associated with statistically significant gains in
      QALYs over UC: 0.041 (0.015, 0.067) for CBT and 0.034 (0.008, 0.060) for MBSR.
      CONCLUSION: In this setting CBT and MBSR have high probabilities of being cost
      effective, and MBSR may be cost saving, as compared with UC for adults with CLBP.
      These findings suggest that MBSR, and to a lesser extent CBT, may provide cost
      effective treatment for CLBP for payers and society. LEVEL OF EVIDENCE: 2.

PMID- 28742757
TI  - Concurrent Validity and Responsiveness of PROMIS Health Domains Among Patients
      Presenting for Anterior Cervical Spine Surgery.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: The aim of this study was to
      determine the validity and responsiveness of Patient-Reported Outcomes
      Measurement Information System (PROMIS) health domains. SUMMARY OF BACKGROUND
      DATA: PROMIS health domains (anxiety, depression, fatigue, pain, physical
      function, satisfaction with participation in social roles, sleep disturbance) may
      measure quality of care and determine minimal important differences (MIDs) after
      spine surgery. We examined concurrent validity of PROMIS domains before and
      PROMIS domain MIDs after anterior cervical spine surgery. METHODS: We included
      148 adults undergoing cervical spine surgery from February 2015 through June
      2016. We determined concurrent validity by correlations of preoperative PROMIS
      domains with legacy measures and responsiveness of PROMIS domains using
      distribution-based and anchor-based criteria (preoperative to postoperative
      change, within 6 months) anchored to treatment expectations (assessed using North
      American Spine Society Patient Satisfaction Index criteria). Statistical
      significance was accepted as P < 0.05. RESULTS: All PROMIS domains showed
      moderate to strong correlations with Neck Disability Index, Short-Form Health
      Survey, version 2 (SF-12v2), and Brief Pain Inventory pain interference and weak
      correlations with intensity of arm/neck pain (except between PROMIS pain and neck
      pain [r = 0.45, P < 0.001] and PROMIS physical function and SF-12v2 physical [r =
      -0.14, P = 0.138] and mental [r = 0.39, P < 0.001] components). PROMIS domains
      were well correlated with Generalized Anxiety Disorder-7 and Patient Health
      Questionnaire-8 except PROMIS physical function (r = -0.29, P = 0.002).
      Distribution-based PROMIS MID estimates ranged from 2.3 to 3.9 points.
      Incorporating cross-sectional and longitudinal anchor-based criteria, final
      PROMIS MID estimates were as follows: anxiety, -5.7; depression, -4.6, fatigue, 
      5.8; pain, -5.2; physical function, 4.5; satisfaction with participation in
      social roles, 4.4; and sleep disturbance, -7.4. CONCLUSION: PROMIS domains are a
      valid assessment of health in this population and were responsive to
      postoperative improvements in symptoms and quality of life. LEVEL OF EVIDENCE: 2.

PMID- 28742758
TI  - Effect of an Adjustable Hinged Operating Table on Lumbar Lordosis During Lumbar
      Surgery.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVES: Quantify the amount of
      lumbar lordosis achieved on a hinged operative table in neutral, flexion, and
      extension. SUMMARY OF BACKGROUND DATA: Hinged operative tables may allow surgeons
      to adjust lumbar spine positioning intraoperatively. The amount of lumbar
      lordosis in neutral, flexion, and extension positions has not been quantified
      prospectively using a hinged table. METHODS: Thirty patients undergoing elective
      lumbar surgery were enrolled. Standing x-rays taken in neutral, maximal flexion,
      and maximal extension were obtained. After prone positioning on a hinged
      operative table, x-rays in neutral, maximal flexion, and maximal extension were
      taken. Total lumbar lordosis was calculated for all six images by two physicians.
      Disc degeneration was graded using Pfirrmann grades. RESULTS: Lumbar lordosis on
      the operative table was 56.5 +/- 2.1, 43.6 +/- 2.2, 63.2 +/- 2.0 compared with
      46.9 +/- 3.1, 33.2 +/- 2.8, 52.3 +/- 3.3 on the standing films in neutral,
      flexion, and extension, respectively. Average flexion (12.9 +/- 1.1) and
      extension (6.7 +/- 1.2) were significantly different from neutral on the table (P
      < 0.001). Lumbar lordosis was significantly higher on the operative table (P <
      0.001). Total range of motion was 19.6 +/- 1.9 on the table and 19.1 +/- 2.0 with
      standing (P = 0.42). Average Pfirrmann disc grade was 2.77 +/- 0.10 that did not
      correlate with range of motion (P = 0.40). CONCLUSION: In this cohort, the hinged
      operative table allowed for a physiologic arc of motion of nearly 20 from flexion
      to extension. A considerable amount of lumbar sagittal motion can be obtained on
      hinged operative tables without decreasing overall lumbar lordosis below
      physiologic levels. LEVEL OF EVIDENCE: 3.

PMID- 28742760
TI  - A Randomized Trial Comparing Clinical Outcomes Between Zero-Profile and
      Traditional Multi-Level Anterior Cervical Discectomy and Fusion Surgery for
      Cervical Myelopathy.
AB  - STUDY DESIGN: Prospective randomized study from a single center OBJECTIVE.: The
      purpose of this study was to compare outcomes between a zero-profile (ZP)
      anterior cervical discectomy and fusion (ACDF) construct to a traditional ACDF
      with anterior plate (ACP) in the treatment of multilevel cervical spondylotic
      myelopathy. SUMMARY OF BACKGROUND DATA: Multi-level cervical spondylotic
      myelopathy can be treated by a variety of techniques, most commonly with
      corpectomy, ACDF, posterior cervical fusion or a combination of the three.
      Examples in the literature of comparative effectiveness of different anterior
      approach types are few. METHODS: A total of 104 patients with multi-level
      cervical spondylotic myelopathy were randomized in equal proportion between
      treated with ACDF and ZP or ACDF with ACP. Clinical efficacy of two groups were
      evaluated preoperatively and at all postoperative time points through two years
      postoperative by the Japanese Orthopedic Association (JOA) score and the neck
      disability index (NDI). Radiographic changes from baseline, including disc height
      and cervical lordosis, were evaluated at the same postoperative time points.
      Complications were assessed perioperatively and through two years postoperative.
      RESULTS: The ZP and ACP ACDF groups demonstrated substantially equivalent JOA,
      NDI, disc height, and lordosis improvements from baseline, which were maintained
      through two years postoperative. Complications occurred in 4% of ZP and 17% of
      ACP patients (p = 0.052), and zero (0%) ZP and four (8%) ACP patients reported
      hoarseness or dysphagia. CONCLUSION: Zero-profile utilized in multi-level ACDF
      may obtained favorable clinical outcomes and a lower postoperative complications.
      LEVEL OF EVIDENCE: 2.

PMID- 28742761
TI  - Preparation and Assessment of an Individualized Navigation Template for Lower
      Cervical Anterior Transpedicular Screw Insertion Using a Three-Dimensional
      Printing Technique.
AB  - STUDY DESIGN: Prospective trial. OBJECTIVE: To establish an individualized
      navigation template for safe and accurate insertion of lower cervical anterior
      transpedicular screw (ATPS) based on a three-dimensional (3D) printing technique.
      SUMMARY OF BACKGROUND DATA: Conventional screw insertion manually under
      fluoroscopy easily leading to deviation of ATPS screw channel, cervical
      instrumentation procedures demand the need for a precise technique for screw
      placement. METHODS: Twenty adult cervical spine specimens (10 men and 10 women,
      with a mean age of 50.29 +/- 6.98) were selected for computed tomography pre- and
      postoperatively. A 3D lower cervical spine model was reconstructed using Mimics
      software to measure the screw-related parameters and generate a reverse template
      with optimal screw channel as well as a prototype using 3D printing. Assisted by
      the navigation template, bilateral ATPS were inserted into the cadavers. RESULTS:
      The mean outer width and height of pedicle were 5.31 +/- 1.23 and 6.78 +/- 1.10
      mm, respectively. The average length, sagittal, and axial angles of the optimal
      screw channel obtained through the optimal entry point were 36.34 +/- 4.39 mm,
      40.67 degrees  +/- 5.10 degrees , and 93.7 degrees  +/- 7.96 degrees ,
      respectively. The adjustable safe ranges of sagittal and axial angles were 3.89
      degrees  +/- 1.13 degrees  and 5.64 degrees  +/- 0.97 degrees , respectively. The
      axial and sagittal accuracies of the 200 screws were 99.5% and 97%, respectively.
      The average deviations of the actual entry point and the preset opening in the X,
      Y, and Z axes were 0.39 +/- 0.43, 0.21 +/- 0.41, and 0.29 +/- 0.14 mm,
      respectively (P > 0.05). CONCLUSION: An individualized ATPS navigation template
      was developed using Mimics software and 3D printing prototyping, based on
      computed tomography, for highly accurate screw insertion. LEVEL OF EVIDENCE: 4.

PMID- 28742763
TI  - Implementation of a National Workplace Wellness Program for Health Workers in
      Botswana.
AB  - : The Botswana workplace wellness program (WWP) for health care workers (HCWs)
      was initiated in 2007. WWP implementation was assessed using a sequential,
      explanatory, mixed methods design including a national implementation assessment
      (27 health districts) and in-depth interviews (n = 38). Level of implementation
      varied across districts with health screening, therapeutic recreation, and health
      promotion implemented more frequently than occupational health activities and
      psychosocial services. Facilitators to WWP implementation included establishment
      of a dedicated, diverse WWP committee; provision of administrative support, and
      integration of activities into organizational culture. Barriers included
      competing priorities related to delivery of health services to clients, limited
      technical ability to deliver occupation health activities and psychosocial
      support, receipt of health services from colleagues, and limited appreciation for
      personal wellness by some HCWs. Ensuring the well-being of HCWs is critical in
      reaching international health goals.

PMID- 28742764
TI  - Linking Compensation and Health Surveillance Data Sets to Improve Knowledge of US
      Coal Miners' Health.
AB  - OBJECTIVE: Increase knowledge of US coal miners' respiratory health by linking
      data from the black lung benefits program (BLBP) and the coal workers' health
      surveillance program (CWHSP). METHODS: BLBP claims data from 2000 through 2013
      was linked to CWHSP data from 1970 through 2016. RESULTS: Overall, 273,644 miners
      participated in CWHSP, 37,548 in BLBP, and 22,903 in both programs. Median age of
      miners at their time of first/only participation in CWHSP was 28 and 32 years,
      respectively. BLBP claimants were older (median age 59). Thirty-nine percent of
      BLBP claimants had not participated in CWHSP. The relative contributions of
      states to participation differed between CWHSP and BLBP. For example, Kentucky
      miners accounted for 18% of CWHSP participants, but 36% of BLPB participants.
      CONCLUSIONS: Many BLBP claimants never appeared in CWHSP, indicating missed
      opportunities for secondary prevention.

PMID- 28742765
TI  - On-the-Job Productivity Losses Among Employees With Health Problems: The Role of
      Work Accommodations.
AB  - OBJECTIVES: Debates about the productivity impact of work accommodations
      typically focus on employment and labor force participation outcomes. This study
      considers whether accommodations mediate on-the-job productivity losses among
      employees who report health problems. METHODS: The study uses ordered logistic
      regression to predict employees' self-reported productivity losses as a function
      of health problems and experiences with needed work accommodations. RESULTS: On
      average, the odds that an employee who did not get a needed accommodation
      reported higher levels of lost productivity are 5.11 times the odds for an
      employee who got a needed accommodation. CONCLUSIONS: Although health problems
      make it difficult for many employees to perform well on the job, accommodations
      could reduce productivity losses in some cases. Nonetheless, more research on the
      impact of specific kinds of accommodations for different chronic conditions is
      warranted.

PMID- 28742766
TI  - Exploration Into the Business Priorities Related to Corporate Engagement in
      Community Health Improvement Partnerships.
AB  - OBJECTIVE: To explore factors that matter to business in making decisions
      regarding engagement in community health improvement efforts. METHODS: Using
      qualitative methods, domains of interest were identified through literature
      reviews and expert interviews. Relevance of the domains in terms of potential
      priorities for action was tested through employer and community stakeholder
      interviews. RESULTS: Factors that employers considered important to sustained
      community collaboration as a business priority included (1) credibility of the
      convener, (2) broad representation of the community, (3) strong mission and
      goals, (4) individual commitment to health, (5) organizational commitment to
      health, and (6) demonstrated commitment from leadership. CONCLUSIONS: Priorities
      have been identified for engaging business in community health efforts.
      Implications for research, practice, and policy include the need for measurement,
      transparency in reporting, and agreement on principles for public-private
      partnership in this area.

PMID- 28742767
TI  - Sedentary Occupation Workers Who Meet the Physical Activity Recommendations Have
      a Reduced Risk for Metabolic Syndrome: A Cross-Sectional Study.
AB  - OBJECTIVE: We tested the hypothesis that sedentary occupation workers who meet
      the physical activity recommendations present a lower risk for metabolic syndrome
      (MetS) than their nonactive counterparts. METHODS: A cross-sectional study
      involving 502 sedentary occupation workers. Physical activity level was self
      reported. MetS was defined by International Diabetes Federation criteria.
      RESULTS: The active group showed lower odds for MetS [odds ratio (OR) 0.52, 95%
      confidence interval (95% CI) 0.27 to 0.98], abdominal obesity (OR 0.36, 95% CI
      0.16 to 0.82), elevated blood pressure (OR 0.47, 95% CI 0.26 to 0.84), and
      reduced high-density lipoprotein cholesterol (OR 0.54, 95% CI 0.31 to 0.93) than
      the sedentary group after adjustments for age, time in job, body mass index, and
      tobacco use. CONCLUSIONS: Sedentary occupation workers who meet the physical
      activity recommendations have a reduced risk for MetS.

PMID- 28742769
TI  - Role of Transesophageal Echocardiography in Surgery for Hemitruncus Arteriosus.

PMID- 28742770
TI  - Role of the Perioperative Surgical Home in Optimizing the Perioperative Use of
      Opioids.
AB  - Several federal agencies have recently noted that the United States is in the
      midst of an unprecedented "opioid epidemic," with an increasing number of opioid
      related overdoses and deaths. Providers currently face 3 population-level, public
      health challenges in providing optimal perioperative pain care: (1) the continued
      lack of overall improvement in the excessive incidence of inadequately treated
      postoperative pain, (2) minimizing or preventing postoperative opioid-related
      side effects, and (3) addressing current opioid prescribing patterns, and the
      accompanying problematic surge in prescription opioid diversion, misuse, abuse,
      addiction, and overdose. In the Perioperative Surgical Home model,
      anesthesiologists and other pain medicine specialists are uniquely qualified and
      positioned to develop, implement, and coordinate a comprehensive perioperative
      analgesic plan, which begins with the formal preoperative patient assessment and
      continues throughout the postdischarge, convalescence period. The scope and
      practice of pain management within the Perioperative Surgical Home should thus
      (a) expand to include routine preoperative patient-level pain-risk stratification
      (including the chronic use of opioid and nonopioid analgesics), (b) address the
      multitude of biopsychosocial factors that contribute to interpatient pain
      variability, and (c) extend and be well coordinated across all 4 phases of the
      surgical pain experience (preoperative, intraoperative, postoperative, and
      postdischarge). Specifically, safe and effective perioperative pain management
      should include a plan of care that is tailored to the individual patient's
      underlying disease(s), presence of a chronic pain condition and preoperative use
      of opioids, and the specific surgical procedure-with evidence-based, multimodal
      analgesic regimens being applied in the vast majority of cases. An iteratively
      evolutionary component of an existing institutional Perioperative Surgical Home
      program can be an integrated Transitional Pain Service, which is modeled directly
      after the well-established prototype at the Toronto General Hospital in Ontario,
      Canada. This multidisciplinary, perioperative Transitional Pain Service seeks to
      modify the pain trajectories of patients who are at increased risk of (a) long
      term, increasing, excessive opioid consumption and/or (b) developing chronic
      postsurgical pain. Like the Perioperative Surgical Home program in which it can
      be logically integrated, such a Transitional Pain Service can serve as the needed
      but missing linkage to improve the continuum of care and perioperative pain
      management for elective, urgent, and emergent surgery. Even if successfully and
      cost-efficiently embedded within an existing Perioperative Surgical Home, a new
      perioperative Transitional Pain Service will require additional resources.

PMID- 28742762
TI  - KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney
      Donors.
AB  - The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice
      Guideline on the Evaluation and Care of Living Kidney Donors is intended to
      assist medical professionals who evaluate living kidney donor candidates and
      provide care before, during and after donation. The guideline development process
      followed the Grades of Recommendation Assessment, Development, and Evaluation
      (GRADE) approach and guideline recommendations are based on systematic reviews of
      relevant studies that included critical appraisal of the quality of the evidence
      and the strength of recommendations. However, many recommendations, for which
      there was no evidence or no systematic search for evidence was undertaken by the
      Evidence Review Team, were issued as ungraded expert opinion recommendations. The
      guideline work group concluded that a comprehensive approach to risk assessment
      should replace decisions based on assessments of single risk factors in
      isolation. Original data analyses were undertaken to produce a "proof-in-concept"
      risk-prediction model for kidney failure to support a framework for quantitative
      risk assessment in the donor candidate evaluation and defensible shared decision
      making. This framework is grounded in the simultaneous consideration of each
      candidate's profile of demographic and health characteristics. The processes and
      framework for the donor candidate evaluation are presented, along with
      recommendations for optimal care before, during, and after donation. Limitations
      of the evidence are discussed, especially regarding the lack of definitive
      prospective studies and clinical outcome trials. Suggestions for future research,
      including the need for continued refinement of long-term risk prediction and
      novel approaches to estimating donation-attributable risks, are also provided.In
      citing this document, the following format should be used: Kidney Disease:
      Improving Global Outcomes (KDIGO) Living Kidney Donor Work Group. KDIGO Clinical
      Practice Guideline on the Evaluation and Care of Living Kidney Donors.
      Transplantation. 2017;101(Suppl 8S):S1-S109.

PMID- 28742771
TI  - Perioperative Amino Acid Infusion for Preventing Hypothermia and Improving
      Clinical Outcomes During Surgery Under General Anesthesia: A Systematic Review
      and Meta-analysis.
AB  - Amino acid (AA) infusion is sometimes selected to avoid hypothermia during
      general anesthesia. However, the widespread clinical use of AA infusion therapy
      has not been established. This study aimed to clarify the evidence that AA
      infusion can increase patient body temperature and improve clinical outcomes
      using the Grading of Recommendations Assessment, Development, and Evaluation
      system. We searched MEDLINE (PubMed), Cochrane Central Register of Controlled
      Trials, and Igaku Chuo Zasshi (Japana Centra Revuo Medicina) in November 2015.
      Studies were reviewed by 2 independent assessors to identify randomized
      controlled trials (RCTs) involving AA infusion compared with placebos during
      surgery under general or combined general/epidural anesthesia. Study quality was
      assessed using the Grading of Recommendations Assessment, Development, and
      Evaluation system and the Cochrane methodology. The primary outcome was
      difference in body temperature before and after perioperative AA infusion.
      Shivering frequency, blood loss volume, postoperative intubation time, and
      hospitalization period were also assessed as clinical outcomes. We analyzed the
      outcome data using a random effect model. From 298 screened titles, 14 RCTs met
      our inclusion criteria, including 626 patients (327 in AA and 299 in placebo
      groups). In 626 participants from 14 RCTs, AA infusion increased body temperature
      by a mean difference (MD) of 0.46 degrees C (95% confidence interval [CI], 0.31
      0.62, low-quality evidence). Regarding other outcomes, AA infusion decreased
      shivering frequency by a risk ratio of 0.34 (95% CI, 0.12-0.94; 7 RCTs, 248
      participants, very low-quality evidence), shortened postoperative intubation time
      by MD of -125 minutes (95% CI, -210 to -38.8; 2 RCTs, 158 participants, moderate
      quality evidence), and shortened the hospitalization period by MD of -1.81 days
      (95% CI, -2.07 to -1.55; 3 RCTs, 230 participants, low-quality evidence) compared
      with placebo. There was no significant difference in the volume of blood loss
      between the 2 groups (standardized MD, -0.20, 95% CI, -0.44 to 0.04; low-quality
      evidence). There was no publication bias. AA infusion in the perioperative period
      increased patient body temperature and improved clinical outcomes compared with
      placebo. However, the evidence to support the use of AA infusion is limited, and
      further large-scale RCTs are required.

PMID- 28742772
TI  - Medication Errors in Pediatric Anesthesia: A Report From the Wake Up Safe Quality
      Improvement Initiative.
AB  - BACKGROUND: Wake Up Safe is a quality improvement initiative of the Society for
      Pediatric Anesthesia that contains a deidentified registry of serious adverse
      events occurring in pediatric anesthesia. The aim of this study was to describe
      and characterize reported medication errors to find common patterns amenable to
      preventative strategies. METHODS: In September 2016, we analyzed approximately 6
      years' worth of medication error events reported to Wake Up Safe. Medication
      errors were classified by: (1) medication category; (2) error type by phase of
      administration: prescribing, preparation, or administration; (3) bolus or
      infusion error; (4) provider type and level of training; (5) harm as defined by
      the National Coordinating Council for Medication Error Reporting and Prevention;
      and (6) perceived preventability. RESULTS: From 2010 to the time of our data
      analysis in September 2016, 32 institutions had joined and submitted data on 2087
      adverse events during 2,316,635 anesthetics. These reports contained details of
      276 medication errors, which comprised the third highest category of events
      behind cardiac and respiratory related events. Medication errors most commonly
      involved opioids and sedative/hypnotics. When categorized by phase of handling,
      30 events occurred during preparation, 67 during prescribing, and 179 during
      administration. The most common error type was accidental administration of the
      wrong dose (N = 84), followed by syringe swap (accidental administration of the
      wrong syringe, N = 49). Fifty-seven (21%) reported medication errors involved
      medications prepared as infusions as opposed to 1 time bolus administrations.
      Medication errors were committed by all types of anesthesia providers, most
      commonly by attendings. Over 80% of reported medication errors reached the
      patient and more than half of these events caused patient harm. Fifteen events
      (5%) required a life sustaining intervention. Nearly all cases (97%) were judged
      to be either likely or certainly preventable. CONCLUSIONS: Our findings
      characterize the most common types of medication errors in pediatric anesthesia
      practice and provide guidance on future preventative strategies. Many of these
      errors will be almost entirely preventable with the use of prefilled medication
      syringes to avoid accidental ampule swap, bar-coding at the point of medication
      administration to prevent syringe swap and to confirm the proper dose, and 2
      person checking of medication infusions for accuracy.

PMID- 28742774
TI  - Improving Adherence to Intraoperative Lung-Protective Ventilation Strategies at a
      University Medical Center.
AB  - BACKGROUND: Intraoperative lung-protective ventilation (ILPV) is defined as tidal
      volumes <8 mL/kg ideal bodyweight and is increasingly a standard of care for
      major abdominal surgical procedures performed under general anesthesia. In this
      study, we report the result of a quality improvement initiative targeted at
      improving adherence to ILPV guidelines in a large academic teaching hospital.
      METHODS: We performed a time-series study to determine whether anesthesia
      provider adherence to ILPV was affected by certain improvement interventions and
      patient ideal body weight (IBW). Tidal volume data were collected at 3 different
      time points for 191 abdominal surgical cases from June 2014 through April 2015.
      Improvement interventions during that period included education at departmental
      grand rounds, creation of a departmental ILPV policy, feedback of tidal volume
      and failure rate data at grand rounds sessions, and reducing default ventilator
      settings for tidal volume. Mean tidal volume per kilogram of ideal body weight
      (VT/kg IBW) and rates of noncompliance with ILPV were analyzed before and after
      the interventions. A survey was administered to assess provider attitudes after
      implementation of improvement interventions. Responses before and after
      interventions and between physician and nonphysician providers were analyzed.
      RESULTS: Reductions in mean VT/kg IBW and rates of failure for providers to use
      ILPV occurred after improvement interventions. Patients with IBW <65 kg received
      higher VT/kg IBW and had higher rates of failure to use ILPV than patients with
      IBW >65 kg. Surveyed providers demonstrated stronger agreement to having
      knowledge and practice consistent with ILPV after interventions. CONCLUSIONS: Our
      interventions improved anesthesia provider adherence to low tidal volume ILPV.
      IBW was found to be an important factor related to provider adherence to ILPV.
      Provider attitudes about their knowledge and practice consistent with ILPV also
      changed with our interventions.

PMID- 28742775
TI  - Estimation of Stroke Volume and Stroke Volume Changes by Electrical Impedance
      Tomography.
AB  - BACKGROUND: Electrical impedance tomography (EIT) is a noninvasive imaging method
      that identifies changes in air and blood volume based on thoracic impedance
      changes. Recently, there has been growing interest in EIT to measure stroke
      volume (SV). The objectives of this study are as follows: (1) to evaluate the
      ability of systolic impedance variations (DeltaZsys) to track changes in SV in
      relation to a baseline condition; (2) to assess the relationship of DeltaZsys and
      SV in experimental subjects; and (3) to identify the influence of body dimensions
      on the relationship between DeltaZsys and SV. METHODS: Twelve Agroceres pigs were
      instrumented with transpulmonary thermodilution catheter and EIT and were
      mechanically ventilated in a random order using different settings of tidal
      volume (VT) and positive end-expiratory pressure (PEEP): VT 10 mL.kg and PEEP 10
      cm H2O, VT 10 mL.kg and PEEP 5 cm H2O, VT 6 mL.kg and PEEP 10 cm H2O, and VT 6
      mL.kg and PEEP 5 cm H2O. After baseline data collection, subjects were submitted
      to hemorrhagic shock and successive fluid challenges. RESULTS: A total of 204
      paired measurements of SV and DeltaZsys were obtained. The 4-quadrant plot showed
      acceptable trending ability with a concordance rate of 91.2%. Changes in
      DeltaZsys after fluid challenges presented an area under the curve of 0.83 (95%
      confidence interval, 0.74-0.92) to evaluate SV changes. Conversely, the linear
      association between DeltaZsys and SV was poor, with R from linear mixed model of
      0.35. Adding information on body dimensions improved the linear association
      between DeltaZsys and SV up to R from linear mixed model of 0.85. CONCLUSIONS:
      EIT showed good trending ability and is a promising hemodynamic monitoring tool.
      Measurements of absolute SV require that body dimensions be taken into account.

PMID- 28742776
TI  - Venovenous Bypass Is Associated With a Lower Incidence of Acute Kidney Injury
      After Liver Transplantation in Patients With Compromised Pretransplant Renal
      Function.
AB  - BACKGROUND: Although the hemodynamic benefits of venovenous bypass (VVB) during
      liver transplantation (LT) are well appreciated, the impact of VVB on
      posttransplant renal function is uncertain. The aim of this study was to
      determine if VVB was associated with a lower incidence of posttransplant acute
      kidney injury (AKI). METHODS: Medical records of adult (>=18 years) patients who
      underwent primary LT between 2004 and 2014 at a tertiary hospital were reviewed.
      Patients who required pretransplant renal replacement therapy and intraoperative
      piggyback technique were excluded. Patients were divided into 2 groups, VVB and
      non-VVB. AKI, determined by the Acute Kidney Injury Network criteria, was
      compared between the 2 groups. Propensity match was used to control selection
      bias that occurred before VVB and multivariable logistic regression was used to
      control confounding factors during and after VVB. RESULTS: Of 1037 adult patients
      who met the study inclusion criteria, 247 (23.8%) received VVB. A total of 442
      patients (221 patients in each group) were matched. Aftermatch patients were
      further divided according to a predicted probability AKI model using preoperative
      creatinine (Cr), VVB, and intraoperative variables into 2 subgroups: normal and
      compromised pretransplant renal functions. In patients with compromised
      pretransplant renal function (Cr >=1.2 mg/dL), the incidence of AKI was
      significantly lower in the VVB group compared with the non-VVB group (37.2% vs
      50.8%; P = .033). VVB was an independent risk factor negatively associated with
      AKI (odds ratio, 0.1; 95% confidence interval, 0.1-0.4; P = .001). Renal
      replacement in 30 days and 1-year recipient mortality were not significantly
      different between the 2 groups. The incidence of posttransplant AKI was not
      significantly different between the 2 groups in patients with normal
      pretransplant renal function (Cr <1.2 mg/dL). CONCLUSIONS: In this large
      retrospective study, we demonstrated that utilization of intraoperative VVB was
      associated with a significantly lower incidence of posttransplant AKI in patients
      with compromised pretransplant renal function. Further studies to assess the role
      of intraoperative VVB in posttransplant AKI are warranted.

PMID- 28742777
TI  - Lack of Association Between the Use of Nerve Blockade and the Risk of Persistent
      Opioid Use Among Patients Undergoing Shoulder Arthroplasty: Evidence From the
      Marketscan Database.
AB  - BACKGROUND: Persistent opioid use following surgery has received increasing
      attention from policymakers, researchers, and clinicians. Perioperative nerve
      blockade has been hypothesized to decrease the risk of persistent opioid use. We
      examined whether nerve blockade was associated with a decreased risk of
      persistent opioid use among patients undergoing shoulder arthroplasty, a
      procedure with high rates of persistent postoperative pain. METHODS: Using health
      care claims data, we constructed a sample of 6695 patients undergoing shoulder
      arthroplasty between 2002 and 2012 and used billing data to identify the
      utilization of nerve blockade. We then used a multivariable logistic regression
      to estimate the association between nerve blockade and 2 measures of opioid use:
      having filled at least 1 prescription for an opioid between postoperative days
      (PODs) 0 and 90, and between POD 91 and 365. This regression adjusted for a
      variety of potential confounders, such as preoperative opioid use and medical
      history. RESULTS: There was no association between nerve blockade and our 2
      measures of persistent opioid use: adjusted odds ratio, 1.12 (97.5% confidence
      interval, 0.939-1.34; P = .15) for opioid use between POD 0 and 90, and adjusted
      odds ratio, 0.997 (97.5% confidence interval, 0.875-1.14; P = .95) for opioid use
      between POD 91 and 365. CONCLUSIONS: Although the use of perioperative nerve
      blockade may offer short-term benefits, in this study, it was not associated with
      a reduction in the risk of persistent opioid use for patients undergoing shoulder
      arthroplasty.

PMID- 28742779
TI  - A Novel Method of Evaluating Key Factors for Success in a Multifaceted Critical
      Care Fellowship Using Data Envelopment Analysis.
AB  - BACKGROUND: The current system of summative multi-rater evaluations and
      standardized tests to determine readiness to graduate from critical care
      fellowships has limitations. We sought to pilot the use of data envelopment
      analysis (DEA) to assess what aspects of the fellowship program contribute the
      most to an individual fellow's success. DEA is a nonparametric, operations
      research technique that uses linear programming to determine the technical
      efficiency of an entity based on its relative usage of resources in producing the
      outcome. DESIGN: Retrospective cohort study. SUBJECTS AND SETTING: Critical care
      fellows (n = 15) in an Accreditation Council for Graduate Medical Education
      (ACGME) accredited fellowship at a major academic medical center in the United
      States. METHODS: After obtaining institutional review board approval for this
      retrospective study, we analyzed the data of 15 anesthesiology critical care
      fellows from academic years 2013-2015. The input-oriented DEA model develops a
      composite score for each fellow based on multiple inputs and outputs. The inputs
      included the didactic sessions attended, the ratio of clinical duty works hours
      to the procedures performed (work intensity index), and the outputs were the
      Multidisciplinary Critical Care Knowledge Assessment Program (MCCKAP) score and
      summative evaluations of fellows. RESULTS: A DEA efficiency score that ranged
      from 0 to 1 was generated for each of the fellows. Five fellows were rated as DEA
      efficient, and 10 fellows were characterized in the DEA inefficient group. The
      model was able to forecast the level of effort needed for each inefficient
      fellow, to achieve similar outputs as their best performing peers. The model also
      identified the work intensity index as the key element that characterized the
      best performers in our fellowship. CONCLUSIONS: DEA is a feasible method of
      objectively evaluating peer performance in a critical care fellowship beyond
      summative evaluations alone and can potentially be a powerful tool to guide
      individual performance during the fellowship.

PMID- 28742780
TI  - Absent Pulmonary Valve in a Case of Tetralogy of Fallot: An Incidental Discovery
      on Intraoperative Transesophageal Echocardiography.

PMID- 28742781
TI  - Do Not Fear the Difficult IV.

PMID- 28742782
TI  - In Response.

PMID- 28742783
TI  - End-Expiratory Occlusion Test Predicts Fluid Responsiveness in Patients With
      Protective Ventilation in the Operating Room.
AB  - BACKGROUND: End-expiratory occlusion test (EEOT) has been proposed to predict
      fluid responsiveness in mechanically ventilated intensive care unit patients. The
      utility of this test during low-tidal-volume ventilation remains uncertain. This
      study aimed to determine whether hemodynamic variations induced by EEOT could
      predict the effect of volume expansion in patients with protective ventilation in
      the operating room. METHODS: Forty-one patients undergoing neurosurgery were
      included. Stroke volume and pulse pressure variations were continuously recorded
      using pulse contour analysis before and immediately after a 30-second EEOT and
      after volume expansion (250 mL saline 0.9% given over 10 minutes). Patients with
      an increase in stroke volume >= 10% after volume expansion were defined as
      responders. RESULTS: Twenty patients were responders to fluid administration.
      EEOT induced a significant increase in stroke volume, which was correlated with
      the stroke volume changes induced by volume expansion (r = 0.55, P < .0001). A 5%
      increase in stroke volume during EEOT discriminated responders to volume
      expansion with a sensitivity of 100% (95% confidence interval [CI], 83%-100%), a
      specificity of 81% (95% CI, 58%-95%), a positive predictive value of 84% (95% CI,
      64%-96%), and a negative predictive value of 100% (95% CI, 80%-100%). The gray
      zone ranged from 4% to 8%, including 17% of patients. The best pulse pressure
      variation threshold was 9%, with a sensitivity of 60% (95% CI, 36%-81%) and
      specificity of 86% (95% CI, 64%-97%). The area under the receiver operating
      characteristics curve generated for changes in stroke volume induced by EEOT
      (0.91, 95% CI, 0.81-1.00) was significantly higher than the one obtained for
      pulse pressure variations (0.75, 95% CI, 0.60-0.90); P < .05. CONCLUSIONS:
      Changes in stroke volume index induced by EEOT can predict fluid responsiveness
      in patients with protective ventilation in the operating room. This test may have
      potential applications.

PMID- 28742784
TI  - Treatment and Complications of Patients With Ipsilateral Acetabular and Femur
      Fractures: A Multicenter Retrospective Analysis.
AB  - OBJECTIVES: The purpose of this study was to review the treatment of patients
      with ipsilateral acetabular and femur fractures to provide descriptive
      demographic data, injury pattern classification, treatment, and evaluate the
      complication profile reflective of current practices. STUDY DESIGN: Multicenter
      retrospective cohort. SETTING: Eight Level 1 Trauma Centers.
      PATIENTS/PARTICIPANTS: One hundred one patients met inclusion criteria.
      INTERVENTION: Surgical treatment of both the acetabular and femur fractures. MAIN
      OUTCOME MEASUREMENTS: The complications evaluated include avascular necrosis,
      heterotopic ossification, posttraumatic arthritis, deep venous thrombosis,
      pulmonary embolism and superficial/deep infection, fracture union, and secondary
      surgeries. RESULTS: Forty-three patients had 31 type fractures (29A; 11B, and
      3C), 60 had 32 type (37A, 8B; 15C), and 8 had 33 type (1A, 4B, 3C) femur
      fractures; 10 patients had combinations involving more than 1 femur fracture
      pattern. There were 35 62A type fractures, 47 62B, and 19 62C acetabular
      fractures. Age of 45 or older was associated with marginal impaction (P = 0.001).
      The aggregate infection rate was 17%. More than 30% of patients required
      secondary surgeries. The rate of avascular necrosis was higher in acetabular
      fractures combined with proximal femur fractures (P < 0.05). The rate of deep
      venous thrombosis was associated with increased age and time to surgical fixation
      (P < 0.05). CONCLUSIONS: We report the largest review of the surgical treatment
      and complications of ipsilateral acetabular and femoral fractures. This study
      provides useful information regarding the complications and provides some
      treatment recommendations regarding these injuries. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 28742785
TI  - An Effective Negative Pressure Wound Therapy-Compatible Local Antibiotic Delivery
      Device.
AB  - OBJECTIVES: The current clinical standard for local antibiotic depot is
      polymethylmethacrylate (PMMA) beads. Unfortunately, these are not ideal and
      negative pressure wound therapy (NPWT) reduces their limited effectiveness.
      Recently, a chitosan sponge has been shown to be an effective carrier of
      antibiotics. Because it acts as a delivery vehicle with increased wound contact
      area instead of an antibiotic depot, it may be more effective. The objectives of
      this study were to determine if (1) a chitosan sponge would be more effective
      than PMMA beads as a local antibiotic delivery device and (2) the chitosan sponge
      remains an effective method of delivery when used in conjunction with NPWT.
      METHODS: Contaminated musculoskeletal wounds were created on the proximal tibia
      of goats; the animals were assigned to 1 of 4 groups (bead pouch, beads with
      NPWT, sponge pouch, and sponge with NPWT). The animals were survived for 48
      hours, and the bacteria in the wound were quantified. The antibiotic levels in
      the blood and within the NPWT canisters were measured throughout the study
      period. RESULTS: After treatment, there were significantly fewer bacteria in
      wounds treated with antibiotic chitosan sponge delivery than antibiotic PMMA bead
      depot (P < 0.05), and NPWT did not reduce the effectiveness of the chitosan
      sponge even though large amounts of vancomycin was found in the canisters. The
      peak serum levels of vancomycin were well below what is considered safe levels.
      CONCLUSIONS: Antibiotic delivery to the wound using a chitosan sponge is
      compatible with NPWT and is more effective than PMMA antibiotic depot. The
      chitosan sponge works in conjunction with NPWT and may improve the outcomes of
      open fracture wounds.

PMID- 28742786
TI  - Proper Distal Placement of Tibial Nail Improves Rate of Malalignment for Distal
      Tibia Fractures.
AB  - OBJECTIVES: We hypothesize that the anatomic center of the distal tibia is just
      lateral and anterior to the center of the distal tibia articular surface in the
      coronal and sagittal planes, respectively, and that placement of the nail along
      this axis results in improved rates of malalignment when treating distal tibia
      fractures. DESIGN: Retrospective study. LEVEL OF EVIDENCE: Therapeutic Level IV.
      See Instructions for Authors for a complete description of levels of evidence.
      SETTING: One Level I and one Level II trauma center. PATIENTS/PARTICIPANTS: Two
      hundred three distal tibia fractures treated with intramedullary nailing (IMN)
      (primary cohort) whose main fracture line extended within 5 cm of the plafond to
      evaluate the rate of malalignment with distal nail placement. Additionally, we
      retrospectively reviewed a secondary cohort of 15 patients with proximal tibia
      fractures treated with intramedullary nailing for evaluation of passive anatomic
      distal nail position. MAIN OUTCOME MEASURES: Primary malalignment <=5 degrees on
      the anteroposterior (AP), mortise, and lateral planes were evaluated in distal
      tibia fractures on perioperative radiographs. RESULTS: Primary Cohort: 85
      patients met inclusion criteria for evaluation in the coronal plane. Overall
      malalignment in the coronal plane was 17.6%. There was a 2.9% (1/34) fracture
      malalignment rate when the nail was placed lateral to the center of the joint
      versus 27.5% (14/51) when placed medial to the center of the joint, with all
      occurring in valgus. This achieved statistical significance (P = 0.04).
      Correlation was highest when measuring the trajectory on mortise view using the
      talus as reference point. When evaluating the sagittal plane, there were 64
      patients that met inclusion criteria with a 48% malalignment rate. Malalignment
      was greatest when the nail was placed in the anterior quadrant 100% (4/4), versus
      50% (22/44) in the anterior middle, and 31.3% (5/16) in the posterior middle
      quadrant. This achieved statistical significance (P = 0.05). No nails were placed
      in the most posterior quadrant. Secondary Cohort: 15 patients met inclusion
      criteria for distal nail placement. The position of the nail in the coronal plane
      was measured on both the anteroposterior and mortise ankle radiographs using both
      the plafond and talus as a reference, whereas sagittal nail placement was
      measured on the lateral ankle radiographs. In the coronal plane, the mean passive
      distal position of the nail when referenced from the lateral cortex was 45.2% of
      the tibia plafond and 45.5% the width of the talus, or just lateral to the center
      of each. In the sagittal plane, passive nail placement was 40% the sagittal width
      of the joint measured from the anterior cortex, or just anterior to the center of
      the joint. CONCLUSIONS: This is the first patient series that defines optimal
      tibial nail placement in the treatment of distal tibia fractures. Distal
      placement of the nail just lateral to the center of the talus and plafond, or
      along mechanical axis of the tibia, results in significantly reduced rates of
      malalignment on the coronal plane when compared to nail placement medial to the
      center of the talus or plafond. Fluoroscopic judgment of distal nail trajectory
      was improved on the mortise view using the talus as a reference when compared to
      using the anteroposterior view. On the sagittal plane, anatomic passive nail
      placement is just anterior to the center of the plafond. However, nonanatomic
      nail placement just posterior to the center of the plafond had a lower incidence
      of malalignment compared with nails placed anterior to the center of the plafond.
      Further study of appropriate nail positioning on the sagittal plane is needed.

PMID- 28742787
TI  - Functional Outcomes of Elderly Patients With Nonoperatively Treated Acetabular
      Fractures That Meet Operative Criteria.
AB  - OBJECTIVES: To report functional outcomes of displaced acetabular fractures
      treated nonoperatively in the geriatric patient population. DESIGN: Retrospective
      case series. SETTING: Two Level I trauma centers. PATIENTS: Twenty-seven patients
      60 years of age or older who sustained displaced acetabular fractures during an
      11-year period. INTERVENTION: Nonoperative treatment. MAIN OUTCOME MEASUREMENTS:
      Primary outcome measurements were Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) scores and Short Form 8 (SF-8) scores. Secondary
      outcome measurements were conversion to open reduction and internal fixation or
      total hip arthroplasty and 1-year mortality. RESULTS: Twenty-six patients
      completed the WOMAC and SF-8 surveys. The overall WOMAC score was 12.9 +/- 15.6
      (range, 0-59.4). The average physical SF-8 was 51.1 +/- 8.7 (range, 30.4-58.6),
      and the average mental SF-8 was 55 +/- 6.2 (range, 30.4-58.6). The 1-year
      mortality rate was 24%. Conversion of treatment occurred in 15% of patients.
      CONCLUSIONS: Elderly patients with fracture patterns that would qualify for
      operative treatment in younger healthy patients had surprisingly good outcome
      scores when treated nonoperatively. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 28742788
TI  - Computer-Assisted Corrective Osteotomy of Malunited Pediatric Radial Neck
      Fractures-Three-Dimensional Postoperative Accuracy and Clinical Outcome.
AB  - Neglected or incorrect treatment of pediatric radial neck fractures may lead to
      symptomatic malunions. Computer-assisted corrective osteotomies with patient
      specific guides have been proposed as a promising technique for the
      reconstruction of malunited long bone deformities. The aim of this study was to
      evaluate the accuracy and clinical outcome of this technique in children with
      malunited fractures of the radial neck. Four children [2 boys, 2 girls; mean age
      12 (10-16) years] underwent computer-assisted closing wedge osteotomy of the
      radial neck. The contralateral uninjured side was used as a reconstruction
      template. Computed tomography were performed 8 weeks postoperatively to confirm
      bony consolidation and to quantify residual 3D rotational and translational
      displacement error. Clinical outcome [pain, range of motion (ROM)] and overall
      satisfaction were documented. Preoperative subluxation of the radial head could
      be corrected in 2 of 3 patients. One patient had to be revised because of
      secondary traumatic loss of reduction. At the last follow-up [mean 16 (range, 12
      24) months], all patients were pain free for activities of daily living
      (preoperative pain: visual analog scale 6). Pain during sport activities could be
      substantially reduced (visual analog scale 8->2). Although the procedure failed
      to improve ROM, none of the patients had limitations regarding work, daily, or
      sports activities. Yet, restricted ROM was considered as a cosmetic problem in 1
      patient. Full consolidation of the osteotomy site, with no signs of avascular
      necrosis of the radial head, was achieved in all patients. The deformity could be
      substantially reduced, from a 3D angle of 13-40 degrees to 3-7 degrees (58%-89%
      deformity correction). Computer-assisted corrective osteotomy is a novel
      technique for the treatment of radial neck malunions that led to adequate pain
      reduction and 3D accuracy of deformity correction in our small case series.
      Despite the lack of improved ROM, all patients were satisfied and would undergo
      the same procedure again.

PMID- 28742789
TI  - Evaluation of Appropriate Venous Thromboembolism Prophylaxis in Patients With
      Orthopaedic Trauma With Symptom-Driven Vascular and Radiographic Studies.
AB  - OBJECTIVE: To evaluate venous thromboembolism (VTE) prophylaxis adherence and
      effectiveness in orthopaedic trauma patients who had vascular or radiographic
      studies showing deep vein thromboses or pulmonary emboli. DESIGN: Retrospective
      review. SETTING: A level I trauma center that independently services a 5-state
      region. PATIENTS: Four hundred seventy-six patients with orthopaedic trauma who
      underwent operative treatments for orthopaedic injuries and had symptom-driven
      diagnostic VTE studies. INTERVENTION: The medical records of patients treated
      surgically between July 2010 and March 2013 were interrogated using a technical
      tool that electronically captures thrombotic event data from vascular and
      radiologic imaging studies by natural language processing. MAIN OUTCOME
      MEASUREMENTS: Patients were evaluated for hospital guideline-directed VTE
      prophylaxis adherence with mechanical or chemical prophylaxis. Patient
      demographics, associated injuries, mechanism of injury, and symptoms that led to
      imaging for a VTE were also assessed. RESULTS: Of the 476 orthopaedic patients
      who met inclusion criteria, 100 (mean age 52.3 median 52, SD 18.3, 70% men) had
      positive VTE studies. Three hundred seventy-six (age 47.3, SD 17.3, 69% men) had
      negative VTE studies. Of the 100 patients with VTE, 63 deep vein thromboses, and
      49 pulmonary emboli were found. Eight-five percent of all patients met hospital
      guideline-VTE prophylaxis standards. CONCLUSION: The study population had better
      than previously reported VTE prophylaxis adherence, however, patients still
      developed VTEs. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 28742790
TI  - Invited Commentary related to: Cost-Utility Analysis of Reconstruction Compared
      With Primary Amputation for Patients With Severe Lower Limb Trauma in Colombia.

PMID- 28742791
TI  - Correlation Between Circulating Tumor DNA Levels and Response to Tyrosine Kinase
      Inhibitors (TKI) Treatment in Non-Small Cell Lung Cancer.
AB  - BACKGROUND Clinical monitoring of EGFR-positive NSCLC patients is important to
      gauge treatment response. The current study addresses the usage of circulating
      tumor DNA (ctDNA) as a prognostic marker during treatment of first-generation
      TKIs. MATERIAL AND METHODS Serial samplings of peripheral blood from 200 EGFR
      positive NSCLC patients were taken. Baseline ctDNA quantification was conducted
      by digital droplet PCR before TKI treatment was administered and compared to
      primary biopsies. Thereafter blood sampling at different treatment cycles were
      measured and assessed for its prognostic and predictive value. RESULTS ctDNA was
      successfully detected in a number of patients and overall concordance rate was
      84%. Importantly, we observed a strong correlation to ctDNA increase with disease
      progression using radiographic scans. In addition to survival analysis, we noted
      patients with the largest ctDNA variations had worst outcome. A significant
      number of EGFR patients during treatment developed a secondary mutation T790M and
      this cohort had worst survival outcome as well. CONCLUSIONS Our study
      demonstrated a highly associative relation of ctDNA to NSCLC patients during
      treatment that can be utilized to gauge treatment response. CtDNA is an
      attractive means compared with conventional core needle biopsies and presents new
      methods for accurately profiling NSCLC disease progression.

PMID- 28742792
TI  - Evidence for genetic association between chromosome 1q loci and predisposition to
      colorectal neoplasia.
AB  - BACKGROUND: A substantial fraction of familial colorectal cancer (CRC) and
      polyposis heritability remains unexplained. This study aimed to identify
      predisposing loci in patients with these disorders. METHODS: Homozygosity mapping
      was performed using 222 563 SNPs in 302 index patients with various colorectal
      neoplasms and 3367 controls. Linkage analysis, exome and whole-genome sequencing
      were performed in a family affected by microsatellite stable CRCs. Candidate
      variants were genotyped in 10 554 cases and 21 480 controls. Gene expression was
      assessed at the mRNA and protein level. RESULTS: Homozygosity mapping revealed a
      disease-associated region at 1q32.3 which was part of the linkage region 1q32.2
      42.2 identified in the CRC family. This includes a region previously associated
      with risk of CRC. Sequencing identified the p.Asp1432Glu variant in the MIA3 gene
      (known as TANGO1 or TANGO) and 472 additional rare, shared variants within the
      linkage region. In both cases and controls the population frequency was 0.02% for
      this MIA3 variant. The MIA3 mutant allele showed predominant mRNA expression in
      normal, cancer and precancerous tissues. Furthermore, immunohistochemistry
      revealed increased expression of MIA3 in adenomatous tissues. CONCLUSIONS: Taken
      together, our two independent strategies associate genetic variations in
      chromosome 1q loci and predisposition to familial CRC and polyps, which warrants
      further investigation.

PMID- 28742793
TI  - Intracrine VEGF signalling mediates colorectal cancer cell migration and
      invasion.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs)
      are key regulators of angiogenesis, affecting endothelial cell survival and
      function. However, the effect of VEGF-VEGFR signalling on tumour cell function is
      not well understood. Our previous studies in colorectal cancer (CRC) cells have
      demonstrated an intracrine VEGF/VEGFR1 signalling mechanism that mediates CRC
      cell survival and chemo-sensitivity. Since extracellular VEGF signalling
      regulates migration of endothelial cells and various tumour cells, we attempted
      to determine whether intracrine VEGF signalling affects CRC cell motility.
      METHODS: Migration and invasion of CRC cells, with and without VEGF or VEGFR1
      depletion, were assayed using transwell migration chambers. Changes in cell
      morphology, epithelial-mesenchymal transition (EMT) markers, and markers of cell
      motility were assessed by immunostaining and western blot. RESULTS: Depletion of
      intracellular VEGF and VEGFR1 in multiple CRC cell lines led to strong inhibition
      of migration and invasion of CRC cells. Except for Twist, there were no
      significant differences in markers of EMT between control and VEGF/VEGFR1
      depleted CRC cells. However, VEGF/VEGFR1-depleted CRC cells demonstrated a
      significant reduction in levels of phosphorylated focal adhesion kinase and its
      upstream regulators pcMET and pEGFR. CONCLUSIONS: Inhibition of intracrine VEGF
      signalling strongly inhibits CRC cell migration and invasion by regulating
      proteins involved in cell motility.

PMID- 28742794
TI  - The cost-effectiveness of screening for ovarian cancer: results from the UK
      Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
AB  - BACKGROUND: To assess the within-trial cost-effectiveness of an NHS ovarian
      cancer screening (OCS) programme using data from UKCTOCS and extrapolate results
      based on average life expectancy. METHODS: Within-trial economic evaluation of no
      screening (C) vs either (1) an annual OCS programme using transvaginal ultrasound
      (USS) or (2) an annual ovarian cancer multimodal screening programme with serum
      CA125 interpreted using a risk algorithm (ROCA) and transvaginal ultrasound as a
      second-line test (MMS), plus comparison of lifetime extrapolation of the no
      screening arm and the MMS programme using both a predictive and a Markov model.
      RESULTS: Using a CA125-ROCA cost of L20, the within-trial results show USS to be
      strictly dominated by MMS, with the MMS vs C comparison returning an incremental
      cost-effectiveness ratio (ICER) of L91 452 per life year gained (LYG). If the
      CA125-ROCA unit cost is reduced to L15, the ICER becomes L77 818 per LYG.
      Predictive extrapolation over the expected lifetime of the UKCTOCS women returns
      an ICER of L30 033 per LYG, while Markov modelling produces an ICER of L46 922
      per QALY. CONCLUSION: Analysis suggests that, after accounting for the lead time
      required to establish full mortality benefits, a national OCS programme based on
      the MMS strategy quickly approaches the current NICE thresholds for cost
      effectiveness when extrapolated out to lifetime as compared with the within-trial
      ICER estimates. Whether MMS could be recommended on economic grounds would depend
      on the confirmation and size of the mortality benefit at the end of an ongoing
      follow-up of the UKCTOCS cohort.

PMID- 28742795
TI  - Cancer-associated fibroblasts promote bone invasion in oral squamous cell
      carcinoma.
AB  - BACKGROUND: The molecular mechanisms involved in the invasion of bone by oral
      squamous cell carcinomas (OSCC) are poorly understood, and little is known about
      the role of cancer-associated fibroblasts (CAF), the presence of which confers a
      poor prognosis. METHODS: Clinicopathological data from 277 OSCC cases involving
      bone resections were reviewed, and 32 cases thoroughly analysed histologically.
      Immunohistochemistry was used to examine alphaSMA, RANKL and OPG. Western
      blotting and qPCR were used to assess myofibroblast (CAF-like) differentiation,
      RANKL and OPG expression in vitro, and RANKL secretion was analysed by ELISA.
      Osteoclastogenesis was examined using TRAP staining, multinucleation and pit
      forming assays. RESULTS: Fibrous stroma intervened between tumour and bone in the
      majority of cases, with no direct contact between cancer cells and bone. RANKL
      and OPG, two proteins key to regulating bone resorption, were expressed in tumour
      cells as well as fibrous stroma adjacent to bone and alphaSMA-positive
      myofibroblastic CAF were consistently seen infiltrating into bone ahead of tumour
      cells. Human primary osteoblasts cultured with conditioned media from human OSCC
      derived cells and human primary CAF showed a significant increase in RANKL and a
      decline in OPG mRNA expression. RANKL secretion was significantly increased in
      primary oral fibroblasts induced to differentiate into a CAF-like phenotype by
      transforming growth factor-beta1 (TGF-beta1) treatment and in primary CAF.
      Indirect co-culture of murine macrophages with conditioned media from CAF
      (experimentally derived and isolated from OSCCs) resulted in a marked increase in
      osteoclastogenesis (in excess of that provoked by cancer cells) determined by
      tartrate-resistant acid phosphatase activity, multinucleation and resorption pit
      formation. CONCLUSIONS: This study is the first to describe a functional role for
      CAFs in bone invasion and turnover, identifying a novel potential therapeutic
      target and diagnostic indicator in this difficult to treat bone invasive
      malignancy.

PMID- 28742796
TI  - Leukocyte telomere length and renal cell carcinoma survival in two studies.
AB  - BACKGROUND: Leukocyte telomere length (LTL) is a potential biomarker of cancer
      prognosis; however, evidence for renal cell carcinoma (RCC) is inconsistent.
      METHODS: We investigated LTL and RCC-specific survival among 684 cases from the
      US kidney cancer study (USKC) and 241 cases from the prostate, lung, colorectal,
      and ovarian cancer screening trial (PLCO). Leukocyte telomere length was measured
      by quantitative polymerase chain reaction, and hazard ratios (HRs) and 95%
      confidence intervals (CIs) computed using multivariable Cox models. RESULTS:
      Short LTL was associated with poorer disease-specific survival in both USKC
      (lowest vs highest quartile: HR: 2.3, 95% CI: 1.2-4.4; P for trend=0.02) and PLCO
      (HR: 2.4, 95% CI: 1.0-5.4; P=0.04). Among USKC cases, the association was
      strongest for stage-I RCC (HR: 5.5, 95% CI: 1.6-19.0; P=0.006). CONCLUSIONS: Our
      findings suggest that shorter LTL is an independent marker of poor RCC prognosis,
      particularly for stage-I disease.

PMID- 28742797
TI  - A comparison of Selective Aortic Arch Perfusion and Resuscitative Endovascular
      Balloon Occlusion of the Aorta for the management of hemorrhage-induced traumatic
      cardiac arrest: A translational model in large swine.
AB  - BACKGROUND: Survival rates remain low after hemorrhage-induced traumatic cardiac
      arrest (TCA). Noncompressible torso hemorrhage (NCTH) is a major cause of
      potentially survivable trauma death. Resuscitative Endovascular Balloon Occlusion
      of the Aorta (REBOA) at the thoracic aorta (Zone 1) can limit subdiaphragmatic
      blood loss and allow for IV fluid resuscitation when intrinsic cardiac activity
      is still present. Selective Aortic Arch Perfusion (SAAP) combines thoracic aortic
      balloon hemorrhage control with intra-aortic oxygenated perfusion to achieve
      return of spontaneous circulation (ROSC) when cardiac arrest has occurred.
      METHODS AND FINDINGS: Male Yorkshire Landrace cross swine (80.0 +/- 6.0 kg)
      underwent anesthesia, instrumentation for monitoring, and splenectomy. TCA was
      induced by laparoscopic liver lobe resection combined with arterial catheter
      blood withdrawal to achieve a sustained systolic blood pressure <10 mmHg, cardiac
      arrest. After 3 min of arrest, swine were allocated to one of three
      interventions: (1) REBOA plus 4 units of IV fresh whole blood (FWB), (2) SAAP
      with oxygenated lactated Ringer's (LR), 1,600 mL/2 min, or (3) SAAP with
      oxygenated FWB 1,600 mL/2 min. Primary endpoint was survival to the end of 60 min
      of resuscitation, a simulated prehospital phase. Thirty animals were allocated to
      3 groups (10 per group)-5 protocol exclusions resulted in a total of 35 animals
      being used. Baseline measurements and time to cardiac arrest were not different
      amongst groups. ROSC was achieved in 0/10 (0%, 95% CI 0.00-30.9) REBOA, 6/10
      (60%, 95% CI 26.2-87.8) SAAP-LR and 10/10 (100%, 95% CI 69.2-100.0) SAAP-FWB
      animals, p < 0.001. Survival to end of simulated 60-minute prehospital
      resuscitation was 0/10 (0%, 95% CI 0.00-30.9) for REBOA, 1/10 (10%, 95% CI 0.25
      44.5) for SAAP-LR and 9/10 (90%, 95% CI 55.5-99.7) for SAAP-FWB, p < 0.001. Total
      FWB infusion volume was similar for REBOA (2,452 +/- 0 mL) and SAAP-FWB (2,250 +/
      594 mL). This study was undertaken in laboratory conditions, and as such may
      have practical limitations when applied clinically. Cardiac arrest in this study
      was defined by intra-aortic pressure monitoring that is not feasible in clinical
      practice, and as such limits the generalizability of findings. Clinical trials
      are needed to determine if the beneficial effects of SAAP-FWB observed in this
      laboratory study will translate into improved survival in clinical practice.
      CONCLUSIONS: SAAP conferred a superior short-term survival over REBOA in this
      large animal model of hemorrhage-induced traumatic cardiac arrest with NCTH. SAAP
      using an oxygen-carrying perfusate was more effective in this study than non
      oxygen carrying solutions in TCA. SAAP can effect ROSC from hemorrhage-induced
      electrocardiographic asystole in large swine.

PMID- 28742798
TI  - Cerebrovascular pressure reactivity monitoring using wavelet analysis in
      traumatic brain injury patients: A retrospective study.
AB  - BACKGROUND: After traumatic brain injury (TBI), the ability of cerebral vessels
      to appropriately react to changes in arterial blood pressure (pressure
      reactivity) is impaired, leaving patients vulnerable to cerebral hypo- or
      hyperperfusion. Although, the traditional pressure reactivity index (PRx) has
      demonstrated that impaired pressure reactivity is associated with poor patient
      outcome, PRx is sometimes erratic and may not be reliable in various clinical
      circumstances. Here, we introduce a more robust transform-based wavelet pressure
      reactivity index (wPRx) and compare its performance with the widely used
      traditional PRx across 3 areas: its stability and reliability in time, its
      ability to give an optimal cerebral perfusion pressure (CPPopt) recommendation,
      and its relationship with patient outcome. METHODS AND FINDINGS: Five hundred and
      fifteen patients with TBI admitted in Addenbrooke's Hospital, United Kingdom
      (March 23rd, 2003 through December 9th, 2014), with continuous monitoring of
      arterial blood pressure (ABP) and intracranial pressure (ICP), were
      retrospectively analyzed to calculate the traditional PRx and a novel wavelet
      transform-based wPRx. wPRx was calculated by taking the cosine of the wavelet
      transform phase-shift between ABP and ICP. A time trend of CPPopt was calculated
      using an automated curve-fitting method that determined the cerebral perfusion
      pressure (CPP) at which the pressure reactivity (PRx or wPRx) was most efficient
      (CPPopt_PRx and CPPopt_wPRx, respectively). There was a significantly positive
      relationship between PRx and wPRx (r = 0.73), and wavelet wPRx was more reliable
      in time (ratio of between-hour variance to total variance, wPRx 0.957 +/- 0.0032
      versus PRx and 0.949 +/- 0.047 for PRx, p = 0.002). The 2-hour interval standard
      deviation of wPRx (0.19 +/- 0.07) was smaller than that of PRx (0.30 +/- 0.13, p
      < 0.001). wPRx performed better in distinguishing between mortality and survival
      (the area under the receiver operating characteristic [ROC] curve [AUROC] for
      wPRx was 0.73 versus 0.66 for PRx, p = 0.003). The mean difference between the
      patients' CPP and their CPPopt was related to outcome for both calculation
      methods. There was a good relationship between the 2 CPPopts (r = 0.814, p <
      0.001). CPPopt_wPRx was more stable than CPPopt_PRx (within patient standard
      deviation 7.05 +/- 3.78 versus 8.45 +/- 2.90; p < 0.001). Key limitations include
      that this study is a retrospective analysis and only compared wPRx with PRx in
      the cohort of patients with TBI. Prior prospective validation is required to
      better assess clinical utility of this approach. CONCLUSIONS: wPRx offers several
      advantages to the traditional PRx: it is more stable in time, it yields a more
      consistent CPPopt recommendation, and, importantly, it has a stronger
      relationship with patient outcome. The clinical utility of wPRx should be
      explored in prospective studies of critically injured neurological patients.

PMID- 28742799
TI  - The new survivors and a new era for trauma research.
AB  - Karim Brohi and Martin Schreiber, Guest Editors of the Special Issue on Trauma,
      describe a new era in exploration of the biology of injury response and
      translation of new opportunities into clinical practice.

PMID- 28742800
TI  - Reducing undiagnosed HIV infection among adolescents in sub-Saharan Africa:
      Provider-initiated and opt-out testing are not enough.
AB  - Community efforts and peer support programs are needed in addition to provider
      initiated and opt-out HIV testing in adolescents, Sheri Weiser and colleagues
      discuss.

PMID- 28742801
TI  - Tracking the return of Aedes aegypti to Brazil, the major vector of the dengue,
      chikungunya and Zika viruses.
AB  - BACKGROUND: Aedes aegypti, commonly known as "the yellow fever mosquito", is of
      great medical concern today primarily as the major vector of dengue, chikungunya
      and Zika viruses, although yellow fever remains a serious health concern in some
      regions. The history of Ae. aegypti in Brazil is of particular interest because
      the country was subjected to a well-documented eradication program during 1940s
      1950s. After cessation of the campaign, the mosquito quickly re-established in
      the early 1970s with several dengue outbreaks reported during the last 30 years.
      Brazil can be considered the country suffering the most from the yellow fever
      mosquito, given the high number of dengue, chikungunya and Zika cases reported in
      the country, after having once been declared "free of Ae. aegypti".
      METHODOLOGY/PRINCIPAL FINDINGS: We used 12 microsatellite markers to infer the
      genetic structure of Brazilian Ae. aegypti populations, genetic variability,
      genetic affinities with neighboring geographic areas, and the timing of their
      arrival and spread. This enabled us to reconstruct their recent history and
      evaluate whether the reappearance in Brazil was the result of re-invasion from
      neighboring non-eradicated areas or re-emergence from local refugia surviving the
      eradication program. Our results indicate a genetic break separating the northern
      and southern Brazilian Ae. aegypti populations, with further genetic
      differentiation within each cluster, especially in southern Brazil.
      CONCLUSIONS/SIGNIFICANCE: Based on our results, re-invasions from non-eradicated
      regions are the most likely scenario for the reappearance of Ae. aegypti in
      Brazil. While populations in the northern cluster are likely to have descended
      from Venezuela populations as early as the 1970s, southern populations seem to
      have derived more recently from northern Brazilian areas. Possible entry points
      are also revealed within both southern and northern clusters that could inform
      strategies to control and monitor this important arbovirus vector.

PMID- 28742802
TI  - Determinants for swine mycoplasmal pneumonia reproduction under experimental
      conditions: A systematic review and recursive partitioning analysis.
AB  - One of the main Mycoplasma hyopneumoniae (M. hyopneumoniae) swine experimental
      model objectives is to reproduce mycoplasmal pneumonia (MP). Unfortunately,
      experimental validated protocols to maximize the chance to successfully achieve
      lung lesions induced by M. hyopneumoniae are not available at the moment. Thus,
      the objective of this work was to identify those factors that might have a major
      influence on the effective development of MP, measured as macroscopic lung
      lesions, under experimental conditions. Data from 85 studies describing M.
      hyopneumoniae inoculation experiments were compiled by means of a systematic
      review and analyzed thereafter. Several variables were considered in the analyses
      such as the number of pigs in the experiment, serological status against M.
      hyopneumoniae, source of the animals, age at inoculation, type of inoculum,
      strain of M. hyopneumoniae, route, dose and times of inoculation, study duration
      and co-infection with other swine pathogens. Descriptive statistics were used to
      depict M. hyopneumoniae experimental model main characteristics whereas a
      recursive partitioning approach, using regression trees, assessed the importance
      of the abovementioned experimental variables as MP triggering factors. A strong
      link between the time period between challenge and necropsies and lung lesion
      severity was observed. Results indicated that the most important factors to
      explain the observed lung lesion score variability were: (1) study duration, (2)
      M. hyopneumoniae strain, (3) age at inoculation, (4) co-infection with other
      swine pathogens and (5) animal source. All other studied variables were not
      relevant to explain the variability on M. hyopneumoniae lung lesions. The results
      provided in the present work may serve as a basis for debate in the search for a
      universally accepted M. hyopneumoniae challenge model.

PMID- 28742803
TI  - The role of supplementary environmental surveillance to complement acute flaccid
      paralysis surveillance for wild poliovirus in Pakistan - 2011-2013.
AB  - BACKGROUND: More than 99% of poliovirus infections are non-paralytic and
      therefore, not detected by acute flaccid paralysis (AFP) surveillance.
      Environmental surveillance (ES) can detect circulating polioviruses from sewage
      without relying on clinical presentation. With extensive ES and continued
      circulation of polioviruses, Pakistan presents a unique opportunity to quantify
      the impact of ES as a supplement to AFP surveillance on overall completeness and
      timeliness of poliovirus detection. METHODS: Genetic, geographic and temporal
      data were obtained for all wild poliovirus (WPV) isolates detected in Pakistan
      from January 2011 through December 2013. We used viral genetics to assess gaps in
      AFP surveillance and ES as measured by detection of 'orphan viruses' (>=1.5%
      different in VP1 capsid nucleotide sequence). We compared preceding detection of
      closely related circulating isolates (>=99% identity) detected by AFP
      surveillance or ES to determine which surveillance system first detected
      circulation before the presentation of each polio case. FINDINGS: A total of
      1,127 WPV isolates were detected by AFP surveillance and ES in Pakistan from 2011
      2013. AFP surveillance and ES combined exhibited fewer gaps (i.e., % orphan
      viruses) in detection than AFP surveillance alone (3.3% vs. 7.7%, respectively).
      ES detected circulation before AFP surveillance in nearly 60% of polio cases (200
      of 346). For polio cases reported from provinces conducting ES, ES detected
      circulation nearly four months sooner on average (117.6 days) than did AFP
      surveillance. INTERPRETATION: Our findings suggest ES in Pakistan is providing
      earlier, more sensitive detection of wild polioviruses than AFP surveillance
      alone. Overall, targeted ES through strategic selection of sites has important
      implications in the eradication endgame strategy.

PMID- 28742804
TI  - Beyond upgrading typologies - In search of a better deal for honey value chains
      in Brazil.
AB  - Selection of value chain strategies by development practitioners and value chain
      participants themselves has been restricted to preset types of upgrading. This
      paper argues for an extension of the range of strategy solutions to value chains.
      An empirical application identifies successful strategies for honey value chains
      in Brazil for 2015-2020. Strategy and performance indicators were selected using
      the value chain Structure-Conduct-Performance (SCP) framework. Experts' opinion
      was elicited in a Delphi for business scenarios, and adaptive conjoint analysis
      was used to identify strategies for increasing production growth and local value
      added. This study identifies important strategies beyond upgrading typologies,
      and finds that important strategies differ by performance goal and scenario. The
      value chain SCP allows searching for promising strategies towards performance-the
      "better deal"-in an integrated way.

PMID- 28742805
TI  - Intra-dialytic hypertension is associated with high mortality in hemodialysis
      patients.
AB  - BACKGROUND: Intra-dialytic hypertension (IDH) is emerging as an important issue
      in hemodialysis patients. Its risk factors and clinical outcomes are unclear.
      METHODS: A total of 73 prevalent hemodialysis patients were enrolled. They
      included 14 (19.2%) patients with baseline IDH and 59 patients without IDH. Their
      clinical parameters, laboratory parameters, and mortality were investigated over
      78 months. RESULTS: The risks factor of IDH included low serum potassium levels,
      low ultrafiltration, and low arm muscle area. Lower median survival was evident
      in the IDH group compared to the non-IDH group, but was not significantly
      different. After adjusting for relevant confounders for age, the IDH group
      displayed 2.846 times higher mortality rate than the non-IDH Group (adjusted
      hazard ratio: 2.846; 95% confidence interval: 1.081-7.490; P = 0.034).
      CONCLUSION: IDH is associated with high mortality in hemodialysis patients.
      Clinicians should be aware of the risk factors. Future research studies are
      needed to explore the mechanisms involved in the association between IDH and
      mortality.

PMID- 28742806
TI  - Long-term follow-up of pulmonary function in Fabry disease: A bi-center
      observational study.
AB  - INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder leading to
      decreased alpha-galactosidase A enzyme activity and subsequent abnormal
      accumulation of glycosphingolipids in various organs. Although histological
      evidence of lung involvement has been demonstrated, the functional impact of
      these changes is less clear. MATERIALS AND METHODS: Adult patients with FD who
      had yearly pulmonary function tests (PFT) at two centers from 1999 thru 2015 were
      eligible for this observational study. Primary outcome measures were the change
      in forced expiratory volume in the first second (FEV1) and FEV1/FVC over time. As
      secondary outcome we investigated sex, smoking, enzyme replacement therapy (ERT),
      residual enzyme activity, and Mainz Severity Score Index as possible predictors.
      RESULTS: 95 patients (41% male, 38.2 +/- 14.5 years) were included. The overall
      prevalence of bronchial obstruction (BO, (FEV1/FVC < 70%)) was 46%, with male
      sex, age and smoking as significant predictors. FEV1 decreased 29 ml per year
      (95% CI -36, -22 ml, p<0.0001). FEV1 decline was significantly higher in males (p
      = 0.009) and in patients on ERT (p = 0.004). Conclusion: Pulmonary involvement
      seems to be a relevant manifestation of Fabry disease, and routine PFTs should
      therefore be included in the multidisciplinary follow-up of these patients.

PMID- 28742807
TI  - Association of coping strategies with mortality and health-related quality of
      life in hemodialysis patients: The Japan Dialysis Outcomes and Practice Patterns
      Study.
AB  - BACKGROUND: Hemodialysis patients are exposed to disease- and treatment-related
      stresses, and use various coping strategies to deal with these stresses. Although
      some studies have reported the association of coping strategies with mortality or
      health-related quality of life (QOL) in some populations, the effect of coping
      strategies on clinical outcomes in hemodialysis patients remains unclear. We
      investigated the association in a longitudinal design among Japanese hemodialysis
      patients. METHODS: We examined Japanese hemodialysis patients who participated in
      the Dialysis Outcomes and Practice Patterns Study (DOPPS) IV, which was conducted
      between 2009 and 2012. The exposure variable was stress coping strategy, as
      assessed using subscales in Coping Strategies Inventory Short Form: problem
      focused engagement, problem-focused disengagement, emotion-focused engagement,
      and emotion-focused disengagement. Hazard ratios were estimated using Cox
      proportional hazard model for all-cause mortality and mean differences for change
      in health-related QOL in 1 year were estimated using a regression model. RESULTS:
      Among 1,354 patients, only problem-focused engagement was significantly
      associated with longer survival; other subscales were not associated with all
      cause mortality after adjustment for potential confounding factors. In terms of
      health-related QOL, the subscale of problem-focused engagement was also
      associated with improvement in physical functioning and mental health among 1,045
      patients. Emotion-focused disengagement was associated with deterioration in
      mental health, but not with change in physical functioning. The other subscales
      were not associated with change in physical functioning or mental health.
      CONCLUSIONS: Among hemodialysis patients, "problem-focused engagement" coping
      strategies were associated with longer survival and also with improvement in
      physical functioning and mental health. To achieve greater longevity and improve
      QOL in hemodialysis patients under ongoing stresses, problem-focused engagement
      should be encouraged.

PMID- 28742808
TI  - Self-help guidebook improved quality of life for patients with irritable bowel
      syndrome.
AB  - BACKGROUND: The primary aim of our study was to evaluate the impact of a
      comprehensive self-help guidebook on the disease related quality of life for
      patients with irritable bowel syndrome (IBS). The secondary aim was to evaluate
      whether the guidebook is less effective in IBS patients with depression,
      somatization disorder or panic disorder as a psychiatric comorbidity. METHODS:
      Prospective observational study. At baseline (t1), patients filled in the
      'Functional Digestive Disorders Quality of Life' (FDDQL) questionnaire and
      received the IBS guidebook together with an explanation of its content and use.
      Depression, anxiety and somatization were evaluated with the Patient Health
      Questionnaire (PHQ). Three (t2) and six months (t3) later, the questionnaire was
      sent by mail to the patients for follow-up evaluation. Data were analyzed with
      repeated measures ANOVA. RESULTS: 71 patients participated (74.6% female). 53
      (74.6%) completed the final assessment at t3 after 6 months. The global FDDQL
      score increased from 49.3 (SD 12.7) at t1 to 64.3 (SD 16.0) at t3 (p < 0.001).
      There was a significant between-subjects effect on the global FDDQL score related
      to depression (p = 0.001), anxiety (p = 0.001) and somatization (p = 0.011).
      Thus, the quality of life of patients with psychosomatic comorbidity was lower at
      baseline, but showed a similar increase within the following six months.
      CONCLUSION: The self-help guidebook significantly improved measured quality of
      life for IBS patients. The use of screening questionnaires like PHQ might be
      valuable to identify patients with more complex problems. This might be helpful
      for them to intensify and adapt therapy. Further research has to evaluate if
      patients with psychological comorbidity are treated more effectively when they
      receive psychotherapy or specific medication in addition to the self-management
      guidebook.

PMID- 28742809
TI  - Dimensions of antenatal care service and the alacrity of mothers towards
      institutional delivery in South and South East Asia.
AB  - BACKGROUND: A number of studies have assessed the effectiveness of antenatal care
      (ANC) on uptake of institutional delivery care. However, none address the issue
      of association between the different components of ANC i.e. ANC component which
      is independent of health care delivery systems (timing and number of ANC visits),
      ANC components which depends on health care delivery systems (specific ANC
      procedures that women receive) with institutional delivery. METHODS: Data for the
      study has been taken from the DHS conducted in the six selected South and South
      East Asian countries during 1998-2013. The two dimensions of ANC are the key
      predictors. The outcome variable is a binary variable, where zero '0' denotes a
      home delivery and one '1' denotes an institutional delivery. In addition to
      probit estimation biprobit estimation method has been used to correct for the
      possible endogeneity. FINDINGS: Analysis suggests that both the factors show a
      positive effect on institutional delivery but the level of associations are
      different. Probit estimation for each country suggests that the association is
      higher for the factor- which depends on health care delivery systems than the
      other factor. After correction of endogeneity through biprobit estimation we get
      the true associations for both the dimensions and it confirms that the ANC
      components which depends on health care delivery systems is more associated with
      the utilization of institutional delivery than the other factor. CONCLUSIONS: The
      content of care may fulfill the women's need and expectations while visiting for
      ANC care. The study suggests that the quality of antenatal care must be improved
      which depends on health care delivery systems to motivates the women to utilize
      the institutional delivery.

PMID- 28742810
TI  - Effect of calcium electroporation in combination with metformin in vivo and
      correlation between viability and intracellular ATP level after calcium
      electroporation in vitro.
AB  - BACKGROUND: Calcium electroporation is a new experimental anti-cancer treatment
      where calcium is internalized into cells by application of short, high voltage
      pulses. Calcium electroporation has been shown to induce tumor necrosis
      associated with ATP depletion while the effect on normal fibroblasts was limited
      when investigated in a 3D in vitro spheroid model. We aimed to investigate the
      effect of calcium electroporation in combination with metformin, a drug that
      affects intracellular ATP level. We also aimed to study the relationship between
      the viability and intracellular ATP levels after calcium electroporation in
      vitro. METHODS: In this study, we investigated the effect of calcium
      electroporation with metformin on NMRI-Foxn1nu mice in vivo on tumor size,
      survival, and intracellular ATP. We further investigated viability and
      intracellular ATP level in vitro after calcium electroporation in two human
      cancer cell lines: Breast (MDA-MB231) and colon (HT29), and in normal human
      fibroblasts (HDF-n), as well as investigating viability in human bladder cancer
      cells (SW780) and human small cell lung cancer cells (H69) where we have
      previously published intracellular ATP levels. RESULTS: Calcium electroporation
      significantly reduced the size and ATP level of bladder cancer tumors treated in
      vivo but no increased effect of metformin combined with calcium electroporation
      was shown on neither tumor size, survival, nor ATP level. Calcium electroporation
      in vitro significantly decreased viability compared with calcium alone (p<0.0001
      for calcium concentrations from 0.5 mM for H69, HDF-n, and MDA-MB231; p<0.0001
      for calcium concentrations from 1 mM for HT29 and SW780). Intracellular ATP
      levels decreased significantly after calcium electroporation (p<0.05), however no
      correlation between intracellular ATP level and viability after treatment was
      observed. CONCLUSION: Calcium electroporation caused reduced tumor size,
      increased survival, and acute ATP depletion in vivo. This effect was not
      augmented by metformin. Calcium electroporation is a possible novel anti-cancer
      treatment that has been shown to cause cell death associated with acute ATP
      depletion in vitro and in vivo.

PMID- 28742811
TI  - Decreased Rhes mRNA levels in the brain of patients with Parkinson's disease and
      MPTP-treated macaques.
AB  - In rodent and human brains, the small GTP-binding protein Rhes is highly
      expressed in virtually all dopaminoceptive striatal GABAergic medium spiny
      neurons, as well as in large aspiny cholinergic interneurons, where it is thought
      to modulate dopamine-dependent signaling. Consistent with this knowledge, and
      considering that dopaminergic neurotransmission is altered in neurological and
      psychiatric disorders, here we sought to investigate whether Rhes mRNA expression
      is altered in brain regions of patients with Parkinson's disease (PD),
      Schizophrenia (SCZ), and Bipolar Disorder (BD), when compared to healthy controls
      (about 200 post-mortem samples). Moreover, we performed the same analysis in the
      putamen of non-human primate Macaca Mulatta, lesioned with the neurotoxin 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Overall, our data indicated
      comparable Rhes mRNA levels in the brain of patients with SCZ and BD, and their
      respective healthy controls. In sharp contrast, the putamen of patients suffering
      from PD showed a significant 35% reduction of this transcript, compared to
      healthy subjects. Interestingly, in line with observations obtained in humans, we
      found 27% decrease in Rhes mRNA levels in the putamen of MPTP-treated primates.
      Based on the established inhibitory influence of Rhes on dopamine-related
      responses, we hypothesize that its striatal downregulation in PD patients and
      animal models of PD might represent an adaptive event of the dopaminergic system
      to functionally counteract the reduced nigrostriatal innervation.

PMID- 28742812
TI  - Broad-range lytic bacteriophages that kill Staphylococcus aureus local field
      strains.
AB  - Staphylococcus aureus is a very successful opportunistic pathogen capable of
      causing a variety of diseases ranging from mild skin infections to life
      threatening sepsis, meningitis and pneumonia. Its ability to display numerous
      virulence mechanisms matches its skill to display resistance to several
      antibiotics, including beta-lactams, underscoring the fact that new anti-S.
      aureus drugs are urgently required. In this scenario, the utilization of lytic
      bacteriophages that kill bacteria in a genus -or even species- specific way, has
      become an attractive field of study. In this report, we describe the isolation,
      characterization and sequencing of phages capable of killing S. aureus including
      methicillin resistant (MRSA) and multi-drug resistant S. aureus local strains
      from environmental, animal and human origin. Genome sequencing and bio
      informatics analysis showed the absence of genes encoding virulence factors,
      toxins or antibiotic resistance determinants. Of note, there was a high
      similarity between our set of phages to others described in the literature such
      as phage K. Considering that reported phages were obtained in different
      continents, it seems plausible that there is a commonality of genetic features
      that are needed for optimum, broad host range anti-staphylococcal activity of
      these related phages. Importantly, the high activity and broad host range of one
      of our phages underscores its promising value to control the presence of S.
      aureus in fomites, industry and hospital environments and eventually on animal
      and human skin. The development of a cocktail of the reported lytic phages active
      against S. aureus-currently under way- is thus, a sensible strategy against this
      pathogen.

PMID- 28742813
TI  - Taste preference changes throughout different life stages in male rats.
AB  - Taste preference, a key component of food choice, changes with aging. However, it
      remains unclear how this occurs. To determine differences in taste preference
      between rats in different life stages, we examined the consumption of taste
      solutions and water using a two-bottle test. Male Sprague-Dawley rats of
      different ages were used: juvenile (3-6 weeks), young adult (8-11 weeks), adult
      (17-20 weeks), middle-aged (34-37 weeks), and old-aged (69-72 weeks). The intakes
      of the high and low concentration solutions presented simultaneously were
      measured. We observed that the old-aged group had lower preference ratios for 0.3
      M sucrose and 0.1 M MSG in comparison with other groups. The preference ratio for
      0.03 mM QHCl was higher in the middle-aged group than in the three younger groups
      and higher in the old-aged group than the juvenile group. The taste preferences
      for HCl and NaCl did not significantly differ among the age groups. The old-aged
      group tended to prefer high concentrations of sucrose, QHCl, NaCl, and MSG to low
      concentrations, indicating age-related decline in taste sensitivity. We also
      aimed to investigate differences between life stages in the electrophysiological
      responses of the chorda tympani nerve, one of the peripheral gustatory nerves, to
      taste stimuli. The electrophysiological recordings showed that aging did not
      alter the function of the chorda tympani nerve. This study showed that aging
      induced alterations in taste preference. It is likely that these alterations are
      a result of functional changes in other peripheral taste nerves, the
      gastrointestinal system, or the central nervous system.

PMID- 28742814
TI  - Wetlands, wild Bovidae species richness and sheep density delineate risk of Rift
      Valley fever outbreaks in the African continent and Arabian Peninsula.
AB  - Rift Valley fever (RVF) is an emerging, vector-borne viral zoonosis that has
      significantly impacted public health, livestock health and production, and food
      security over the last three decades across large regions of the African
      continent and the Arabian Peninsula. The potential for expansion of RVF outbreaks
      within and beyond the range of previous occurrence is unknown. Despite many large
      national and international epidemics, the landscape epidemiology of RVF remains
      obscure, particularly with respect to the ecological roles of wildlife reservoirs
      and surface water features. The current investigation modeled RVF risk throughout
      Africa and the Arabian Peninsula as a function of a suite of biotic and abiotic
      landscape features using machine learning methods. Intermittent wetland, wild
      Bovidae species richness and sheep density were associated with increased
      landscape suitability to RVF outbreaks. These results suggest the role of
      wildlife hosts and distinct hydrogeographic landscapes in RVF virus circulation
      and subsequent outbreaks may be underestimated. These results await validation by
      studies employing a deeper, field-based interrogation of potential wildlife hosts
      within high risk taxa.

PMID- 28742815
TI  - IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response
      after severe trauma: A reverse translation study from a human cohort to a mouse
      trauma model.
AB  - BACKGROUND: The immunosuppression and immune dysregulation that follows severe
      injury includes type 2 immune responses manifested by elevations in interleukin
      (IL) 4, IL5, and IL13 early after injury. We hypothesized that IL33, an alarmin
      released early after tissue injury and a known regulator of type 2 immunity,
      contributes to the early type 2 immune responses after systemic injury. METHODS
      AND FINDINGS: Blunt trauma patients admitted to the trauma intensive care unit of
      a level I trauma center were enrolled in an observational study that included
      frequent blood sampling. Dynamic changes in IL33 and soluble suppression of
      tumorigenicity 2 (sST2) levels were measured in the plasma and correlated with
      levels of the type 2 cytokines and nosocomial infection. Based on the
      observations in humans, mechanistic experiments were designed in a mouse model of
      resuscitated hemorrhagic shock and tissue trauma (HS/T). These experiments
      utilized wild-type C57BL/6 mice, IL33-/- mice, B6.C3(Cg)-Rorasg/sg mice deficient
      in group 2 innate lymphoid cells (ILC2), and C57BL/6 wild-type mice treated with
      anti-IL5 antibody. Severely injured human blunt trauma patients (n = 472, average
      injury severity score [ISS] = 20.2) exhibited elevations in plasma IL33 levels
      upon admission and over time that correlated positively with increases in IL4,
      IL5, and IL13 (P < 0.0001). sST2 levels also increased after injury but in a
      delayed manner compared with IL33. The increases in IL33 and sST2 were
      significantly greater in patients that developed nosocomial infection and organ
      dysfunction than similarly injured patients that did not (P < 0.05). Mechanistic
      studies were carried out in a mouse model of HS/T that recapitulated the early
      increase in IL33 and delayed increase in sST2 in the plasma (P < 0.005). These
      studies identified a pathway where IL33 induces ILC2 activation in the lung
      within hours of HS/T. ILC2 IL5 up-regulation induces further IL5 expression by
      CXCR2+ lung neutrophils, culminating in early lung injury. The major limitations
      of this study are the descriptive nature of the human study component and the
      impact of the potential differences between human and mouse immune responses to
      polytrauma. Also, the studies performed did not permit us to make conclusions
      about the impact of IL33 on pulmonary function. CONCLUSIONS: These results
      suggest that IL33 may initiate early detrimental type 2 immune responses after
      trauma through ILC2 regulation of neutrophil IL5 production. This IL33-ILC2-IL5
      neutrophil axis defines a novel regulatory role for ILC2 in acute lung injury
      that could be targeted in trauma patients prone to early lung dysfunction.

PMID- 28742816
TI  - A mixture of sparse coding models explaining properties of face neurons related
      to holistic and parts-based processing.
AB  - Experimental studies have revealed evidence of both parts-based and holistic
      representations of objects and faces in the primate visual system. However, it is
      still a mystery how such seemingly contradictory types of processing can coexist
      within a single system. Here, we propose a novel theory called mixture of sparse
      coding models, inspired by the formation of category-specific subregions in the
      inferotemporal (IT) cortex. We developed a hierarchical network that constructed
      a mixture of two sparse coding submodels on top of a simple Gabor analysis. The
      submodels were each trained with face or non-face object images, which resulted
      in separate representations of facial parts and object parts. Importantly, evoked
      neural activities were modeled by Bayesian inference, which had a top-down
      explaining-away effect that enabled recognition of an individual part to depend
      strongly on the category of the whole input. We show that this explaining-away
      effect was indeed crucial for the units in the face submodel to exhibit
      significant selectivity to face images over object images in a similar way to
      actual face-selective neurons in the macaque IT cortex. Furthermore, the model
      explained, qualitatively and quantitatively, several tuning properties to facial
      features found in the middle patch of face processing in IT as documented by
      Freiwald, Tsao, and Livingstone (2009). These included, in particular, tuning to
      only a small number of facial features that were often related to geometrically
      large parts like face outline and hair, preference and anti-preference of extreme
      facial features (e.g., very large/small inter-eye distance), and reduction of the
      gain of feature tuning for partial face stimuli compared to whole face stimuli.
      Thus, we hypothesize that the coding principle of facial features in the middle
      patch of face processing in the macaque IT cortex may be closely related to
      mixture of sparse coding models.

PMID- 28742817
TI  - Temporal profile of intracranial pressure and cerebrovascular reactivity in
      severe traumatic brain injury and association with fatal outcome: An
      observational study.
AB  - BACKGROUND: Both intracranial pressure (ICP) and the cerebrovascular pressure
      reactivity represent the dysregulation of pathways directly involved in traumatic
      brain injury (TBI) pathogenesis and have been used to inform clinical management.
      However, how these parameters evolve over time following injury and whether this
      evolution has any prognostic importance have not been studied. METHODS AND
      FINDINGS: We analysed the temporal profile of ICP and pressure reactivity index
      (PRx), examined their relation to TBI-specific mortality, and determined if the
      prognostic relevance of these parameters was affected by their temporal profile
      using mixed models for repeated measures of ICP and PRx for the first 240 hours
      from the time of injury. A total of 601 adults with TBI, admitted between
      September 2002 to January 2016, and with high-resolution continuous monitoring
      from a single centre, were studied. At 6 months postinjury, 133 (19%) patients
      had a fatal outcome; of those, 88 (78%) died from nonsurvivable TBI or brain
      death. The difference in mean ICP between those with a fatal outcome and
      functional survivors was only significant for the first 168 hours after injury
      (all p < 0.05). For PRx, those patients with a fatal outcome also had a higher
      (more impaired) PRx throughout the first 120 hours after injury (all p < 0.05).
      The separation of ICP and PRx was greatest in the first 72 hours after injury.
      Mixed models demonstrated that the explanatory power of the PRx decreases over
      time; therefore, the prognostic weight assigned to PRx should similarly decrease.
      However, the ability of ICP to predict a fatal outcome remained relatively stable
      over time. As control of ICP is the central purpose of TBI management, it is
      likely that some of the information that is reflected in the natural history of
      ICP changes is no longer apparent because of therapeutic intervention.
      CONCLUSIONS: We demonstrated the temporal evolution of ICP and PRx and their
      relationship with fatal outcome, indicating a potential early prognostic and
      therapeutic window. The combination of dynamic monitoring variables and their
      time profile improved prediction of outcome. Therefore, time-driven dynamic
      modelling of outcome in patients with severe TBI may allow for more accurate and
      clinically useful prediction models. Further research is needed to confirm and
      expand on these findings.

PMID- 28742818
TI  - First identification of a recombinant form of hepatitis C virus in Austrian
      patients by full-genome next generation sequencing.
AB  - Hepatitis C virus (HCV) intergenotypic recombinant forms have been reported for
      various HCV genotypes/subtypes in several countries worldwide. In a recent study,
      four patients living in Austria had been identified to be possibly infected with
      a recombinant HCV strain. To clarify results and determine the point of
      recombination, full-genome next-generation sequencing using the Illumina MiSeq v2
      300 cycle kit (Illumina, San Diego, CA, USA) was performed in the present study.
      Samples of all of the patients contained the recombinant HCV strain 2k/1b. The
      point of recombination was found to be within the HCV NS2 gene between nucleotide
      positions 3189-3200 based on H77 numbering. While three of four patients were
      male and had migration background from Chechnya (n = 2) and Azerbaijan (n = 1),
      the forth patient was a female born in Austria. Three of the four patients
      including the female had intravenous drug abuse as a risk factor for HCV
      transmission. While sequencing techniques are limited to a few specialized
      laboratories, a genotyping assay that uses both ends of the HCV genome should be
      employed to identify patients infected with a recombinant HCV strain. The correct
      identification of recombinant strains also has an impact considering the tailored
      choice of anti-HCV treatment.

PMID- 28742819
TI  - The science of rapid start-From the when to the how of antiretroviral initiation.
AB  - In this Perspective linked to Koenig and colleagues, Elvin Geng and Diane Havlir
      discuss the next challenges for implementation research around rapid start
      antiretroviral treatment.

PMID- 28742820
TI  - Facilitators and barriers to physical activity in people with chronic low back
      pain: A qualitative study.
AB  - BACKGROUND: For medical teams, one of the main objectives of rehabilitation for
      people with chronic low back pain is adherence to physical activity (PA).
      OBJECTIVE: The objective of this study was to identify PA barriers and
      facilitators in this population. METHODS: This qualitative study included 4
      discussion groups and 16 semi-structured interviews conducted among people with
      non-specific chronic low back pain who were involved in a specific rehabilitation
      program or seen in primary care settings. RESULTS: Three main themes were
      identified: physical factors, psychological factors and socio-environmental
      factors. The main barrier to PA practice is pain. Psychological barriers were
      associated with the difficulty in integrating PA in the person's daily life.
      Environmental barriers were dominated by lack of time. Facilitators identified
      associated the supervised nature of the physical activity (supervision by
      professionals) and group practice, which improved people's adherence. CONCLUSION:
      The results of this study will allow teams to target relevant educational
      objectives for these people and develop dedicated self-management programs.

PMID- 28742821
TI  - Evolution of the cAMP-dependent protein kinase (PKA) catalytic subunit isoforms.
AB  - The 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase, or
      protein kinase A (PKA), pathway is one of the most versatile and best studied
      signaling pathways in eukaryotic cells. The two paralogous PKA catalytic subunits
      Calpha and Cbeta, encoded by the genes PRKACA and PRKACB, respectively, are among
      the best understood model kinases in signal transduction research. In this work,
      we explore and elucidate the evolution of the alternative 5' exons and the
      splicing pattern giving rise to the numerous PKA catalytic subunit isoforms. In
      addition to the universally conserved Calpha1/Cbeta1 isoforms, we find kinase
      variants with short N-termini in all main vertebrate classes, including the sperm
      specific Calpha2 isoform found to be conserved in all mammals. We also describe,
      for the first time, a PKA Calpha isoform with a long N-terminus, paralogous to
      the PKA Cbeta2 N-terminus. An analysis of isoform-specific variation highlights
      residues and motifs that are likely to be of functional importance.

PMID- 28742822
TI  - Metal ion coordination in the E. coli Nudix hydrolase dihydroneopterin
      triphosphate pyrophosphatase: New clues into catalytic mechanism.
AB  - Dihydroneopterin triphosphate pyrophosphatase (DHNTPase), a member of the Mg2+
      dependent Nudix hydrolase superfamily, is the recently-discovered enzyme that
      functions in the second step of the pterin branch of the folate biosynthetic
      pathway in E. coli. DHNTPase is of interest because inhibition of enzymes in
      bacterial folate biosynthetic pathways is a strategy for antibiotic development.
      We determined crystal structures of DHNTPase with and without activating, Mg2+
      mimicking metals Co2+ and Ni2+. Four metal ions, identified by anomalous
      scattering, and stoichiometrically confirmed in solution by isothermal titration
      calorimetry, are held in place by Glu56 and Glu60 within the Nudix sequence
      motif, Glu117, waters, and a sulfate ion, of which the latter is further
      stabilized by a salt bridge with Lys7. In silico docking of the DHNTP substrate
      reveals a binding mode in which the pterin ring moiety is nestled in a largely
      hydrophobic pocket, the beta-phosphate activated for nucleophilic attack overlays
      with the crystallographic sulfate and is in line with an activated water
      molecule, and remaining phosphate groups are stabilized by all four identified
      metal ions. The structures and binding data provide new details regarding
      DHNTPase metal requirements, mechanism, and suggest a strategy for efficient
      inhibition.

PMID- 28742823
TI  - Genome-wide identification and analysis of the MADS-box gene family in bread
      wheat (Triticum aestivum L.).
AB  - The MADS-box genes encode transcription factors with key roles in plant growth
      and development. A comprehensive analysis of the MADS-box gene family in bread
      wheat (Triticum aestivum) has not yet been conducted, and our understanding of
      their roles in stress is rather limited. Here, we report the identification and
      characterization of the MADS-box gene family in wheat. A total of 180 MADS-box
      genes classified as 32 Malpha, 5 Mgamma, 5 Mdelta, and 138 MIKC types were
      identified. Evolutionary analysis of the orthologs among T. urartu, Aegilops
      tauschii and wheat as well as homeologous sequences analysis among the three sub
      genomes in wheat revealed that gene loss and chromosomal rearrangements occurred
      during and/or after the origin of bread wheat. Forty wheat MADS-box genes that
      were expressed throughout the investigated tissues and development stages were
      identified. The genes that were regulated in response to both abiotic stresses
      (i.e., phosphorus deficiency, drought, heat, and combined drought and heat) and
      biotic stresses (i.e., Fusarium graminearum, Septoria tritici, stripe rust and
      powdery mildew) were detected as well. A few notable MADS-box genes were
      specifically expressed in a single tissue and those showed relatively higher
      expression differences between the stress and control treatment. The expression
      patterns of considerable MADS-box genes differed from those of their orthologs in
      Brachypodium, rice, and Arabidopsis. Collectively, the present study provides new
      insights into the possible roles of MADS-box genes in response to stresses and
      will be valuable for further functional studies of important candidate MADS-box
      genes.

PMID- 28742824
TI  - How do rehomed laboratory beagles behave in everyday situations? Results from an
      observational test and a survey of new owners.
AB  - When laboratory dogs are rehomed into private households, they experience an
      extreme change in their life situation. They leave their familiar, limited
      environment in the research facility and encounter a multitude of animate and
      inanimate stimuli in their new home. Although literature reports have described
      the experiences with rehoming as being mostly positive, scientific observations
      of the dogs in everyday situations have not been done. Hence, we conducted an
      observational test with 74 laboratory beagles 6 weeks after adoption in their new
      homes. This test included standardized tasks and elements; the dogs were observed
      during specific interactions with their new owners and during a walk.
      Furthermore, the owners of these 74 and of 71 additional dogs participated in
      standardized phone interviews 1 and 12 weeks after adoption, during which they
      answered questions about the dogs' behavior in everyday situations. In the
      observational test, the dogs behaved mostly friendly towards humans and dogs,
      were tolerant during manipulations by the owner and were relaxed during the walk,
      even in traffic. Eighty percent (of n = 71) of the dogs walked well behaved on
      the leash without pulling. According to the interviews, the majority of the dogs
      showed desired, friendly and relaxed behavior, and the survey results reflected
      the bonding between dog and owner. The analysis of a possible influence of
      various factors (age, sex, origin, etc.) using mixed regression models confirmed
      the results from two previous behavior tests and interviews. Specifically, dogs
      that had been bred in the research facility scored significantly better than dogs
      that the research facility had purchased from commercial laboratory dog breeders
      (p = 0.0113). The results of this study demonstrate a successful adaptation of
      the rehomed beagles to their new life situation.

PMID- 28742825
TI  - Impact of maternal and neonatal health initiatives on inequity in maternal health
      care utilization in Bangladesh.
AB  - BACKGROUND: Despite remarkable progress in maternal and child health, inequity
      persists in maternal care utilization in Bangladesh. Government of Bangladesh
      (GOB) with technical assistance from United Nation Population Fund (UNFPA),
      United Nation Children's Fund (UNICEF) and World Health Organization (WHO)
      started implementing Maternal and Neonatal Health Initiatives in selected
      districts of Bangladesh (MNHIB) in 2007 with an aim to reduce inequity in
      healthcare utilization. This study examines the effect of MNHIB on inequity in
      maternal care utilization. METHOD: Two surveys were carried out in four districts
      in Bangladesh- baseline in 2008 and end-line in 2013. The baseline survey
      collected data from 13,206 women giving birth in the preceding year and in end
      line 7,177 women were interviewed. Inequity in maternal healthcare utilization
      was calculated pre and post-MNHIB using rich-to-poor ratio and concentration
      index. RESULTS: Mean age of respondents were 23.9 and 24.6 years in 2008 and 2013
      respectively. Utilization of pregnancy-related care increased for all
      socioeconomic strata between these two surveys. The concentration indices (CI)
      for various maternal health service utilization in 2013 were found to be lower
      than the indices in 2008. However, in comparison to contemporary BDHS data in
      nearby districts, MNHIB was successful in reducing inequity in receiving ANC from
      a trained provider (CI: 0.337 and 0.272), institutional delivery (CI: 0.435 in
      2008 to 0.362 in 2013), and delivery by skilled personnel (CI: 0.396 and 0.370).
      CONCLUSIONS: Overall use of maternal health care services increased in post-MNHIB
      year compared to pre-MNHIB year and inequity in maternal service utilization
      declined for three indicators out of six considered in the paper. The reductions
      in CI values for select maternal care indicators imply that the program has been
      successful not only in improving utilization of maternal health services but also
      in lowering inequality of service utilization across socioeconomic groups.
      Maternal health programs, if properly designed and implemented, can improve
      access, partially overcoming the negative effects of socioeconomic disparities.

PMID- 28742826
TI  - Macromolecular biosynthetic parameters and metabolic profile in different life
      stages of Leishmania braziliensis: Amastigotes as a functionally less active
      stage.
AB  - It was recently hypothesized that Leishmania amastigotes could constitute a semi
      quiescent stage characterized by low replication and reduced metabolic activity.
      This concept developed with Leishmania (Leishmania) mexicana and Leishmania
      (Leishmania) major models might explain numerous clinical and sub-clinical
      features of Leishmania (Viannia) braziliensis infections, like reactivation of
      the disease, non-response to chemotherapy or asymptomatic infections. We compared
      here in vitro the proliferative capability of L. (V.) braziliensis amastigotes
      and promastigotes, assessed the expression of key molecular parameters and
      performed metabolomic analysis. We found that contrary to the highly
      proliferative promastigotes, amastigotes (axenic and intracellular) do not show
      evidence of extensive proliferation. In parallel, amastigotes showed a
      significant decrease of (i) the kDNA mini-circle abundance, (ii) the
      intracellular ATP level, (iii) the ribosomal components: rRNA subunits 18S and
      28S alpha and ribosomal proteins RPS15 and RPL19, (iv) total RNA and protein
      levels. An untargeted metabolomic study identified clear differences between the
      different life stages: in comparison to logarithmic promastigotes, axenic
      amastigotes showed (a) a strong decrease of 14 essential and non-essential amino
      acids and eight metabolites involved in polyamine synthesis, (b) extensive
      changes in the phospholipids composition and (c) increased levels of several
      endogenous and exogenous sterols. Altogether, our results show that L. (V.)
      braziliensis amastigotes can show a phenotype with negligible rate of
      proliferation, a lower capacity of biosynthesis, a reduced bio-energetic level
      and a strongly altered metabolism. Our results pave the way for further
      exploration of quiescence among amastigotes of this species.

PMID- 28742827
TI  - The relationship between coronary artery distensibility and fractional flow
      reserve.
AB  - Discordance between angiography-based anatomical assessment of coronary stenosis
      severity and fractional flow reserve (FFR) has been attributed to several factors
      including lesion length and irregularity, and the myocardial territory supplied
      by the target vessel. We sought to examine if coronary arterial distensibility is
      an independent contributor to this discordance. There were two parts to this
      study. The first consisted of "in silico" models of 26 human coronary arteries.
      Computational fluid dynamics-derived FFR was calculated for fully rigid,
      partially distensible and fully distensible models of the 26 arteries. The second
      part of the study consisted of 104 patients who underwent coronary angiography
      and FFR measurement. Distensibility at the lesion site (DistensibilityMLA) and
      for the reference vessel (DistensibilityRef) was determined by analysing three
      dimensional angiography images during end-systole and end-diastole. Computational
      fluid dynamics-derived FFR was 0.67+/-0.19, 0.70+/-0.18 and 0.75+/-0.17 (P<0.001)
      in the fully rigid, partially distensible and fully distensible models
      respectively. FFR correlated with both DistensibilityMLA (r = 0.36, P<0.001) and
      DistensibilityRef (r = 0.44, P<0.001). Two-way ANCOVA analysis revealed that
      DistensibilityMLA (F (1, 100) = 4.17, p = 0.031) and percentage diameter stenosis
      (F (1, 100) = 60.30, p < 0.01) were both independent predictors of FFR. Coronary
      arterial distensibility is a novel, independent determinant of FFR, and an
      important factor contributing to the discordance between anatomical and
      functional assessment of stenosis severity.

PMID- 28742828
TI  - Feasibility of rigid 3D image registration of high-resolution peripheral
      quantitative computed tomography images of healing distal radius fractures.
AB  - For accurate analysis of bone formation and resorption during fracture healing,
      correct registration of follow-up onto baseline image is required. A per-fragment
      approach could improve alignment compared to standard registration based on the
      whole fractured region. In this exploratory study, we tested the effect of
      fragment size and displacement on a per-fragment registration, and compared the
      results of this per-fragment registration to the results of the standard
      registration in two stable fractures and one unstable fracture. To test the
      effect of fragment size and displacement, high-resolution peripheral quantitative
      computed tomography (HR-pQCT) scans of three unfractured radii were divided into
      subvolumes. Different displacements in x-, y, or z-direction or rotations around
      each axis were applied, and each subvolume was registered onto the initial volume
      to realign it. Next, registration of follow-up onto baseline scan was performed
      in two stable and one unstable fracture. After coarsely aligning the follow-up
      onto the baseline scan, a more accurate registration was performed of the whole
      fracture, i.e. the standard registration, and of each fracture fragment
      separately, i.e. per-fragment registration. Alignment was checked using overlay
      images showing baseline, follow-up and overlap between these scans, and by
      comparing correlation coefficients between the standard and per-fragment
      registration. Generally, subvolumes as small as 300 mm3 that were displaced up to
      0.82 mm in x- or y-, or up to 1.64 mm in z-direction could be realigned
      correctly. For the fragments of all fractures, correlation coefficients were
      higher after per-fragment registration compared to standard registration. Most
      improvement was found in the unstable fracture and one fragment of the unstable
      fracture did not align correctly. This exploratory study showed that image
      registration of individual subvolumes, such as fracture fragments, is feasible in
      both stable and unstable fractures, and leads to better alignment of these
      fragments compared to an approach that is based on registration using the whole
      fractured region. This result is promising for additional analysis of bone
      formation and resorption in HR-pQCT studies on fracture healing.

PMID- 28742829
TI  - Community burden of undiagnosed HIV infection among adolescents in Zimbabwe
      following primary healthcare-based provider-initiated HIV testing and
      counselling: A cross-sectional survey.
AB  - BACKGROUND: Children living with HIV who are not diagnosed in infancy often
      remain undiagnosed until they present with advanced disease. Provider-initiated
      testing and counselling (PITC) in health facilities is recommended for high-HIV
      prevalence settings, but it is unclear whether this approach is sufficient to
      achieve universal coverage of HIV testing. We aimed to investigate the change in
      community burden of undiagnosed HIV infection among older children and
      adolescents following implementation of PITC in Harare, Zimbabwe. METHODS AND
      FINDINGS: Over the course of 2 years (January 2013-January 2015), 7 primary
      health clinics (PHCs) in southwestern Harare implemented optimised, opt-out PITC
      for all attendees aged 6-15 years. In February 2015-December 2015, we conducted a
      representative cross-sectional survey of 8-17-year-olds living in the 7
      communities served by the study PHCs, who would have had 2 years of exposure to
      PITC. Knowledge of HIV status was ascertained through a caregiver questionnaire,
      and anonymised HIV testing was carried out using oral mucosal transudate (OMT)
      tests. After 1 participant taking antiretroviral therapy was observed to have a
      false negative OMT result, from July 2015 urine samples were obtained from all
      participants providing OMTs and tested for antiretroviral drugs to confirm HIV
      status. Children who tested positive through PITC were identified from among
      survey participants using gender, birthdate, and location. Of 7,146 children in
      4,251 eligible households, 5,486 (76.8%) children in 3,397 households agreed to
      participate in the survey, and 141 were HIV positive. HIV prevalence was 2.6%
      (95% CI 2.2%-3.1%), and over a third of participants with HIV were undiagnosed
      (37.7%; 95% CI 29.8%-46.2%). Similarly, among the subsample of 2,643 (48.2%)
      participants with a urine test result, 34.7% of those living with HIV were
      undiagnosed (95% CI 23.5%-47.9%). Based on extrapolation from the survey sample
      to the community, we estimated that PITC over 2 years identified between 18% and
      42% of previously undiagnosed children in the community. The main limitation is
      that prevalence of undiagnosed HIV was defined using a combination of 3 measures
      (OMT, self-report, and urine test), none of which were perfect. CONCLUSIONS:
      Facility-based approaches are inadequate in achieving universal coverage of HIV
      testing among older children and adolescents. Alternative, community-based
      approaches are required to meet the Joint United Nations Programme on HIV/AIDS
      (UNAIDS) target of diagnosing 90% of those living with HIV by 2020 in this age
      group.

PMID- 28742830
TI  - Regulatory effects of zinc on cadmium-induced cytotoxicity in chronic
      inflammation.
AB  - OBJECTIVES: Zinc (Zn) has major effects on immune system activation while Cadmium
      (Cd) has anti-inflammatory and anti-proliferative effects in several chronic
      inflammatory contexts. The aim of this work was to investigate by which
      mechanisms Zn could compete with Cd and eventually counteract its deleterious
      effects. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as
      a model of chronic inflammation; osteoarthritis (OA) synoviocytes were used as
      control. METHODS: Cell/medium fractionation constants were analyzed for different
      metals by inductively-coupled-plasma mass-spectrometry by comparison to the 70Zn
      spike. Interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-alpha) were
      used to mimic inflammation. Gene expression of ZIP-8 importer, metallothioneins-1
      (MT-1s) and the ratio between metalloprotease-3 and the tissue inhibitor of
      metalloproteinases (MMP-3)/TIMP-1) were evaluated after pre-exposure to cytokines
      and Cd, with or without the addition of exogenous Zn (0.9 ppm). Cell viability
      was measured by neutral red assay and IL-6 production by ELISA. RESULTS:
      Synoviocytes selectively absorbed and retained Cd in comparison to Zn. Metal
      import increased with IL-17/TNF-alpha exposure, through the enhanced ZIP-8
      expression. Zn did not modify ZIP-8 expression, while Cd reduced it (p<0.05). Zn
      induced a reduction of Cd-induced MT-1s expression, in particular of MT-1X (3
      fold), and subsequently the final intra-cellular content of Cd. By reducing Cd
      accumulation in cells, Zn reversed Cd anti-proliferative and anti-inflammatory
      effects but preserved the low MMP-3/TIMP-1 ratio induced by Cd, which was
      enhanced by inflammatory conditions. CONCLUSION: Zinc counteracts the deleterious
      effect of Cd by reducing its import and accumulation in the cell, without the
      reactivation of destructive pathways such as MMPs.

PMID- 28742831
TI  - Deterministic stability and random behavior of a Hepatitis C model.
AB  - The deterministic stability of a model of Hepatitis C which includes a term
      defining the effect of immune system is studied on both local and global scales.
      Random effect is added to the model to investigate the random behavior of the
      model. The numerical characteristics such as the expectation, variance and
      confidence interval are calculated for random effects with two different
      distributions from the results of numerical simulations. In addition, the
      compliance of the random behavior of the model and the deterministic stability
      results is examined.

PMID- 28742832
TI  - The relationship between movement speed and duration during soccer matches.
AB  - The relationship between the time duration of movement (t(dur)) and related
      maximum possible power output has been studied and modeled under many conditions.
      Inspired by the so-called power profiles known for discontinuous endurance sports
      like cycling, and the critical power concept of Monod and Scherrer, the aim of
      this study was to evaluate the numerical characteristics of the function between
      maximum horizontal movement velocity (HSpeed) and t(dur) in soccer. To evaluate
      this relationship, GPS data from 38 healthy soccer players and 82 game
      participations (>=30 min active playtime) were used to select maximum HSpeed for
      21 distinct t(dur) values (between 0.3 s and 2,700 s) based on moving medians
      with an incremental t(dur) window-size. As a result, the relationship between
      HSpeed and Log(t(dur)) appeared reproducibly as a sigmoidal decay function, and
      could be fitted to a five-parameter equation with upper and lower asymptotes, and
      an inflection point, power and decrease rate. Thus, the first three parameters
      described individual characteristics if evaluated using mixed-model analysis.
      This study shows for the first time the general numerical relationship between
      t(dur) and HSpeed in soccer games. In contrast to former descriptions that have
      evaluated speed against power, HSpeed against t(dur) always yields a sigmoidal
      shape with a new upper asymptote. The evaluated curve fit potentially describes
      the maximum moving speed of individual players during the game, and allows for
      concise interpretations of the functional state of team sports athletes.

PMID- 28742833
TI  - Translational approaches to coagulopathy after trauma: Towards targeted
      treatment.
AB  - Mitchell J. Cohen discusses why trauma care must go beyond restoring perfusion to
      target disorders of inflammation and coagulation in severely injured patients.

PMID- 28742834
TI  - Contacts in the last 90,000 years over the Strait of Gibraltar evidenced by
      genetic analysis of wild boar (Sus scrofa).
AB  - Contacts across the Strait of Gibraltar in the Pleistocene have been studied in
      different research papers, which have demonstrated that this apparent barrier has
      been permeable to human and fauna movements in both directions. Our study, based
      on the genetic analysis of wild boar (Sus scrofa), suggests that there has been
      contact between Africa and Europe through the Strait of Gibraltar in the Late
      Pleistocene (at least in the last 90,000 years), as shown by the partial analysis
      of mitochondrial DNA. Cytochrome b and the control region from North African wild
      boar indicate a close relationship with European wild boar, and even some
      specimens belong to a common haplotype in Europe. The analyses suggest the
      transformation of the wild boar phylogeography in North Africa by the emergence
      of a natural communication route in times when sea levels fell due to climatic
      changes, and possibly through human action, since contacts coincide with both the
      Last Glacial period and the increasing human dispersion via the strait.

PMID- 28742835
TI  - A checklist of the bats of Peninsular Malaysia and progress towards a DNA barcode
      reference library.
AB  - Several published checklists of bat species have covered Peninsular Malaysia as
      part of a broader region and/or in combination with other mammal groups. Other
      researchers have produced comprehensive checklists for specific localities within
      the peninsula. To our knowledge, a comprehensive checklist of bats specifically
      for the entire geopolitical region of Peninsular Malaysia has never been
      published, yet knowing which species are present in Peninsular Malaysia and their
      distributions across the region are crucial in developing suitable conservation
      plans. Our literature search revealed that 110 bat species have been documented
      in Peninsular Malaysia; 105 species have precise locality records while five
      species lack recent and/or precise locality records. We retrieved 18 species from
      records dated before the year 2000 and seven species have only ever been recorded
      once. Our search of Barcode of Life Datasystems (BOLD) found that 86 (of the 110)
      species have public records of which 48 species have public DNA barcodes
      available from bats sampled in Peninsular Malaysia. Based on Neighbour-Joining
      tree analyses and the allocation of DNA barcodes to Barcode Index Number system
      (BINs) by BOLD, several DNA barcodes recorded under the same species name are
      likely to represent distinct taxa. We discuss these cases in detail and highlight
      the importance of further surveys to determine the occurences and resolve the
      taxonomy of particular bat species in Peninsular Malaysia, with implications for
      conservation priorities.

PMID- 28742836
TI  - The impact of MET, IGF-1, IGF1R expression and EGFR mutations on survival of
      patients with non-small-cell lung cancer.
AB  - INTRODUCTION: To compare the efficacy of silver in situ hybridization (SISH) and
      immunohistochemistry (IHC) in detecting MET and IGF1R alterations and to
      investigate their prevalence and prognostic significance. A possible correlation
      between MET receptor expression, MET gene alterations and the two most frequent
      occurring EGFR gene mutations was also investigated. MATERIALS AND METHODS: Stage
      I to IIIA tumors from 326 patients with NSCLC were immunohistochemically tested
      for protein expression of MET and IGF-1. Their cytoplasmic expression was
      compared with the gene copy number of the MET and IGF1Rgenes by SISH in paraffin
      embedded, formalin-fixed material. Correlations were made with the
      immunohistochemical expression of two frequent EGFR mutations and
      clinicopathological variables. Univariate and multivariate survival analyses was
      used to evaluate the prognostic efficacy of the tested markers. RESULTS: In
      univariate analyses, high cytoplasmic MET expression showed a significant
      negative prognostic effect in adenocarcinoma patients (p = 0.026). MET gene to
      chromosome 7 ratio was a significant positive prognostic marker (p = 0.005),
      probably only due to the highly negative prognostic significance of chromosome 7
      polysomy (p = 0.002). High IGF1R gene copy number was a negative prognostic
      marker for all NSCLC patients (p = 0.037). In the multivariate analysis, polysomy
      of chromosome 7 in tumor cells correlated significantly and independently with a
      poor prognosis (p = 0.011). In patients with adenocarcinoma, a high cytoplasmic
      MET expression was an independent negative prognostic marker (p = 0.013). In
      males a high IGF1R gene copy number to chromosome 15 count ratio was
      significantly and independently correlated to a poor prognosis (p = 0.018).
      CONCLUSION: MET protein expression provides superior prognostic information
      compared with SISH. Polysomy of chromosome 7 is an independent negative
      prognostic factor in NSCLC patients. This finding has an important implication
      while examining genes located on chromosome 7 by means of SISH. High IGF1R gene
      copy number to chromosome 15 count ratio is an independent predictor of inferior
      survival in male patients with primary NSCLC.

PMID- 28742837
TI  - Risk factors associated with posttraumatic stress disorder in US veterans: A
      cohort study.
AB  - OBJECTIVE: To assess the association between clinical and exercise test factors
      and the development of posttraumatic stress disorder (PTSD) in US Veterans.
      PATIENTS AND METHODS: Exercise capacity, demographics and clinical variables were
      assessed in 5826 veterans (mean age 59.4 +/- 11.5 years) from the Veterans
      Affairs Healthcare System in Palo Alto, CA. The study participants underwent
      routine clinical exercise testing between the years 1987 and 2011. The study end
      point was the development of PTSD. RESULTS: A total of 723 (12.9%) veterans were
      diagnosed with PTSD after a mean follow-up of 9.6 +/- 5.6 years. Drug abuse (HR:
      1.98, CI: 1.33-2.92, p = .001), current smoking (HR: 1.57, CI: 1.35-2.24, p
      <.001), alcohol abuse (HR: 1.58, CI: 1.12-2.24, p = .009), history of chest pain
      (HR: 1.48, CI: 1.25-1.75, p <.001) and higher exercise capacity (HR: 1.03, CI:
      1.01-1.05, p = .003) were strong independent risk factors for PTSD in a
      univariate model. Physical activity pattern was not associated with PTSD in
      either the univariate or multivariate models. In the final multivariate model,
      current smoking (HR: 1.30, CI: 1.10-1.53, p = .002) history of chest pain (HR:
      1.37, CI: 1.15-1.63, p <.001) and younger age (HR: 0.97, CI: 0.97-0.98, p <.001)
      were significantly associated to PTSD. CONCLUSIONS: Onset of PTSD is
      significantly associated with current smoking, history of chest pain and younger
      age. Screening veterans with multiple risk factors for symptoms of PTSD should
      therefore be taken into account.

PMID- 28742838
TI  - Identification of novel antigen candidates for a tuberculosis vaccine in the
      adult zebrafish (Danio rerio).
AB  - Tuberculosis (TB) remains a major global health challenge and the development of
      a better vaccine takes center stage in fighting the disease. For this purpose,
      animal models that are capable of replicating the course of the disease and are
      suitable for the early-stage screening of vaccine candidates are needed. A
      Mycobacterium marinum infection in adult zebrafish resembles human TB. Here, we
      present a pre-clinical screen for a DNA-based tuberculosis vaccine in the adult
      zebrafish using an M. marinum infection model. We tested 15 antigens representing
      different types of mycobacterial proteins, including the Resuscitation Promoting
      factors (Rpf), PE/PPE protein family members, other membrane proteins and
      metabolic enzymes. The antigens were expressed as GFP fusion proteins,
      facilitating the validation of their expression in vivo. The efficiency of the
      antigens was tested against a low-dose intraperitoneal M. marinum infection (~ 40
      colony forming units), which mimics a primary M. tuberculosis infection. While
      none of the antigens was able to completely prevent a mycobacterial infection,
      four of them, namely RpfE, PE5_1, PE31 and cdh, led to significantly reduced
      bacterial burdens at four weeks post infection. Immunization with RpfE also
      improved the survival of the fish against a high-dose intraperitoneal injection
      with M. marinum (~ 10.000 colony forming units), resembling the disseminated form
      of the disease. This study shows that the M. marinum infection model in adult
      zebrafish is suitable for the pre-clinical screening of tuberculosis vaccines and
      presents RpfE as a potential antigen candidate for further studies.

PMID- 28742839
TI  - Flavonols reduce aortic atherosclerosis lesion area in apolipoprotein E deficient
      mice: A systematic review and meta-analysis.
AB  - Diets rich in flavonoids have been reported to have beneficial effects in the
      primary prevention of cardiovascular events. There are limited data, however, on
      the cardiovascular benefits of purified flavonoids. The aim of this systematic
      review and meta-analysis was to examine the reported effects of isolated
      flavonoids on aortic atherosclerosis in a mouse model. Medline, Pubmed, Science
      direct and Web of Science were searched to identify studies which examined the
      effect of isolated flavonoids on aortic atherosclerosis in apolipoprotein E
      deficient mice. A meta-analysis was performed to determine the overall effect of
      the flavonoids, and sub-analyses were performed to compare the effects of the
      flavonols and flavan-3-ols. Eleven studies, which examined a total of 208 mice
      receiving a flavonoid and 126 control mice, were included. Overall the flavonoids
      significantly reduced aortic atherosclerosis (SMD 1.10, 95% CI 0.69, 1.51). Of
      the 18 flavonoid interventions examined 12 were flavonols and 3 were flavan-3
      ols. Sub-analyses suggested that the flavonols (SMD 1.31, 95% CI 0.66, 1.91) but
      not the flavan-3-ols (SMD 0.33, 95% CI -0.19, 0.85) significantly decreased
      atherosclerosis area. Of the eleven studies, only one examined histological
      markers of atherosclerosis plaque stability. Most studies did not report blinding
      of outcome assessors or reproducibility of the primary outcome, and did not
      justify the sample size used and flavonoid dose administered. Based on the
      included studies, the flavonols appear to be the most effective flavonoids for
      reducing aortic atherosclerotic lesion area in apolipoprotein E deficient mice.

PMID- 28742840
TI  - Glaucomatous changes in lamina pores shape within the lamina cribrosa using wide
      bandwidth, femtosecond mode-locked laser OCT.
AB  - PURPOSE: The lamina cribrosa (LC) is known to play a critical role in the
      pathogenesis of glaucoma. Although it has been reported that striae-shaped or
      slit-shaped lamina pores are more frequent in eyes with primary open angle
      glaucoma (POAG), this observation is based only on fundus photography. The
      primary object of this study is to perform layer-by-layer comparisons of the
      shape of lamina pores within the LC in vivo. DESIGN: Cross-sectional study.
      METHODS: Optic nerve head B-scans were obtained using custom-made broad
      wavelength optical coherence tomography with a mode-locked laser. A total of 300
      single B-scans per eye were obtained and three-dimensional images were rendered
      from these image sequences to obtain 2-MUm thin-slice en face images of the LC.
      Elongation indices (EIs) of the lamina pores were measured from the anterior
      surface (AS) of the LC to the deeper layers in 40-MUm increments. RESULTS:
      Thirteen eyes from 10 primary open angle glaucoma (POAG) patients of mean
      deviation -15.2 (-16.5, -12.9) (median [25,75 percentile]) dB and 10 eyes from 7
      normal controls were studied. Although the EI value was not significantly
      different between the superior, temporal and inferior regions of the LC at any
      depth level in either group, it was greater at the AS than at the 40 MUm and 80
      MUm depth levels (P < .001) in both groups, and was greater in the POAG group
      only at the AS and 40 MUm depth level (P <= .05). After adjustment for age and
      refraction, the effects of depth and presence of POAG on the EI value remained
      significant. Also, the severity of glaucoma and depth were significant factors
      associated with EI in multivariate analysis. CONCLUSIONS: Elongation of lamina
      pores was significantly more evident at the anterior surface and the 40-MUm depth
      level of the LC in POAG eyes than in normal eyes, suggesting that nerve fiber
      bundles passing through the LC were under greater stress in the anterior layers
      of the LC.

PMID- 28742841
TI  - Bacillus sp. JR3 esterase LipJ: A new mesophilic enzyme showing traces of a
      thermophilic past.
AB  - A search for extremophile enzymes from ancient volcanic soils in El Hierro Island
      (Canary Islands, Spain) allowed isolation of a microbial sporulated strain
      collection from which several enzymatic activities were tested. Isolates were
      obtained after sample cultivation under several conditions of nutrient contents
      and temperature. Among the bacterial isolates, supernatants from the strain
      designated JR3 displayed high esterase activity at temperatures ranging from 30
      to 100 degrees C, suggesting the presence of at least a hyper-thermophilic
      extracellular lipase. Sequence alignment of known thermophilic lipases allowed
      design of degenerated consensus primers for amplification and cloning of the
      corresponding lipase, named LipJ. However, the cloned enzyme displayed maximum
      activity at 30 degrees C and pH 7, showing a different profile from that observed
      in supernatants of the parental strain. Sequence analysis of the cloned protein
      showed a pentapeptide motif -GHSMG- distinct from that of thermophilic lipases,
      and much closer to that of esterases. Nevertheless, the 3D structural model of
      LipJ displayed the same folding as that of thermophilic lipases, suggesting a
      common evolutionary origin. A phylogenetic study confirmed this possibility,
      positioning LipJ as a new member of the thermophilic family of bacterial lipases
      I.5. However, LipJ clusters in a clade close but separated from that of
      Geobacillus sp. thermophilic lipases. Comprehensive analysis of the cloned enzyme
      suggests a common origin of LipJ and other bacterial thermophilic lipases, and
      highlights the most probable divergent evolutionary pathway followed by LipJ,
      which during the harsh past times would have probably been a thermophilic enzyme,
      having lost these properties when the environment changed to more benign
      conditions.

PMID- 28742842
TI  - New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti
      proliferative mechanism of action and encapsulation into PLGA microspheres.
AB  - The synthesis and molecular characterization of new isatin-based hydrazonoindolin
      2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of
      the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75
      (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were
      the most active congeners against the tested human cancer cell lines with average
      IC50 values of 4.77, 3.39 and 2.37 MUM, respectively, as compared with the
      reference isatin-based drug, sunitinib, which exhibited an average IC50 value of
      8.11 MUM. Compound 7e was selected for further pharmacological evaluation in
      order to gain insight into its possible mechanism of action. It increased caspase
      3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively,
      at 10 MUM and it caused a decrease in the percentage of cells in the G1 phase of
      the cell cycle with a corresponding increase in the S-phase. In addition,
      compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with
      an apparent IC50 value of 3.8 MUM. The 7e-loaded PLGA microspheres were prepared
      using a modified emulsion-solvent diffusion method. The average encapsulation
      efficiency of the 7e-loaded PLGA microspheres was 85% +/- 1.3. While, the in
      vitro release profile of the 7e-loaded microspheres was characterized by slow and
      continuous release of compound 7e during 21 days and the release curve was fitted
      to zero order kinetics. Incorporation of 7e into PLGA microspheres improved its
      in vitro anti-proliferative activity toward the human cancer cell line A549 after
      120 h incubation period with an IC50 value less than 0.8 MUM.

PMID- 28742843
TI  - Sequencing of the complete mitochondrial genomes of eight freshwater snail
      species exposes pervasive paraphyly within the Viviparidae family
      (Caenogastropoda).
AB  - Phylogenetic relationships among snails (Caenogastropoda) are still unresolved,
      and many taxonomic categories remain non-monophyletic. Paraphyly has been
      reported within a large family of freshwater snails, Viviparidae, where the
      taxonomic status of several species remains questionable. As many endemic Chinese
      viviparid species have become endangered during the last few decades, this
      presents a major obstacle for conservation efforts. Mitochondrial genomes
      (mitogenomes) carry a large amount of data, so they can often provide a much
      higher resolution for phylogenetic analyses in comparison to the traditionally
      used molecular markers. To help resolve their phylogenetic relationships, the
      complete mitogenomes of eight Chinese viviparid snails, Viviparus chui,
      Cipangopaludina chinensis, C. ussuriensis, C. dianchiensis (endangered), Margarya
      melanioides (endangered), M. monodi (critically endangered), Bellamya quadrata
      and B. aeruginosa, were sequenced and compared to almost all of the available
      caenogastropod mitogenomes. Viviparidae possess the largest mitogenomes (16 392
      to 18 544 bp), exhibit the highest A+T bias (72.5% on average), and some exhibit
      unique gene orders (a rearrangement of the standard MYCWQGE box), among the
      Caenogastropoda. Apart from the Vermetidae family and Cerithioidea superfamily,
      which possessed unique gene orders, the remaining studied caenogastropod
      mitogenomes exhibited highly conserved gene order, with minimal variations.
      Maximum likelihood and Bayesian inference analyses, used to reconstruct the
      phylogenetic relationships among 49 almost complete (all 37 genes) caenogastropod
      mitogenomes, produced almost identical tree topologies. Viviparidae were divided
      into three clades: a) Margarya and Cipangopaludina (except C. ussuriensis), b)
      Bellamya and C. ussuriensis, c) Viviparus chui. Our results present evidence that
      some Cipangopaludina species (dianchiensis and cathayensis) should be renamed
      into the senior genus Margarya. The phylogenetic resolution obtained in this
      study is insufficient to fully resolve the relationships within the 'b' clade,
      but if C. chinensis proves to be a valid representative of the genus, C.
      ussuriensis may have to be reassigned a different genus (possibly Bellamya, or
      even a new genus). Non-monophyly also remains pervasive among the higher (above
      the family-level) Caenogastropod taxonomic classes. Gene order distance matrix
      produced a different phylogenetic signal from the nucleotide sequences, which
      indicates a limited usability of this approach for inferring caenogastropod
      phylogenies. As phenotypic homoplasy appears to be widespread among some
      viviparid genera, in order to effectively protect the rapidly diminishing endemic
      Viviparid populations in China, further detailed molecular phylogenetic studies
      are urgently needed to resolve the taxonomic status of several species.

PMID- 28742844
TI  - Control of RUNX-induced repression of Notch signaling by MLF and its partner DnaJ
      1 during Drosophila hematopoiesis.
AB  - A tight regulation of transcription factor activity is critical for proper
      development. For instance, modifications of RUNX transcription factors dosage are
      associated with several diseases, including hematopoietic malignancies. In
      Drosophila, Myeloid Leukemia Factor (MLF) has been shown to control blood cell
      development by stabilizing the RUNX transcription factor Lozenge (Lz). However,
      the mechanism of action of this conserved family of proteins involved in leukemia
      remains largely unknown. Here we further characterized MLF's mode of action in
      Drosophila blood cells using proteomic, transcriptomic and genetic approaches.
      Our results show that MLF and the Hsp40 co-chaperone family member DnaJ-1
      interact through conserved domains and we demonstrate that both proteins bind and
      stabilize Lz in cell culture, suggesting that MLF and DnaJ-1 form a chaperone
      complex that directly regulates Lz activity. Importantly, dnaj-1 loss causes an
      increase in Lz+ blood cell number and size similarly as in mlf mutant larvae.
      Moreover we find that dnaj-1 genetically interacts with mlf to control Lz level
      and Lz+ blood cell development in vivo. In addition, we show that mlf and dnaj-1
      loss alters Lz+ cell differentiation and that the increase in Lz+ blood cell
      number and size observed in these mutants is caused by an overactivation of the
      Notch signaling pathway. Finally, using different conditions to manipulate Lz
      activity, we show that high levels of Lz are required to repress Notch
      transcription and signaling. All together, our data indicate that the MLF/DnaJ-1
      dependent increase in Lz level allows the repression of Notch expression and
      signaling to prevent aberrant blood cell development. Thus our findings establish
      a functional link between MLF and the co-chaperone DnaJ-1 to control RUNX
      transcription factor activity and Notch signaling during blood cell development
      in vivo.

PMID- 28742845
TI  - Evaluation of K-ras and p53 expression in pancreatic adenocarcinoma using the
      cancer genome atlas.
AB  - Genetic alterations in K-ras and p53 are thought to be critical in pancreatic
      cancer development and progression. However, K-ras and p53 expression in
      pancreatic adenocarcinoma have not been systematically examined in The Cancer
      Genome Atlas (TCGA) Data Portal. Information regarding K-ras and p53 alterations,
      mRNA expression data, and protein/protein phosphorylation abundance was retrieved
      from The Cancer Genome Atlas (TCGA) databases, and analyses were performed by the
      cBioPortal for Cancer Genomics. The mutual exclusivity analysis showed that
      events in K-ras and p53 were likely to co-occur in pancreatic adenocarcinoma (Log
      odds ratio = 1.599, P = 0.006). The graphical summary of the mutations showed
      that there were hotspots for protein activation. In the network analysis, no
      solid association between K-ras and p53 was observed in pancreatic
      adenocarcinoma. In the survival analysis, neither K-ras nor p53 were associated
      with both survival events. As in the data mining study in the TCGA databases, our
      study provides a new perspective to understand the genetic features of K-ras and
      p53 in pancreatic adenocarcinoma.

PMID- 28742846
TI  - Endophytic fungal communities of Polygonum acuminatum and Aeschynomene
      fluminensis are influenced by soil mercury contamination.
AB  - The endophytic fungal communities of Polygonum acuminatum and Aeschynomene
      fluminensis were examined with respect to soil mercury (Hg) contamination. Plants
      were collected in places with and without Hg+2 for isolation and identification
      of their endophytic root fungi. We evaluated frequency of colonization, number of
      isolates and richness, indices of diversity and similarity, functional traits
      (hydrolytic enzymes, siderophores, indoleacetic acid, antibiosis and metal
      tolerance) and growth promotion of Aeschynomene fluminensis inoculated with
      endophytic fungi on soil with mercury. The frequency of colonization, structure
      and community function, as well as the abundant distribution of taxa of
      endophytic fungi were influenced by mercury contamination, with higher endophytic
      fungi in hosts in soil with mercury. The presence or absence of mercury in the
      soil changes the profile of the functional characteristics of the endophytic
      fungal community. On the other hand, tolerance of lineages to multiple metals is
      not associated with contamination. A. fluminensis depends on its endophytic
      fungi, since plants free of endophytic fungi grew less than expected due to
      mercury toxicity. In contrast plants containing certain endophytic fungi showed
      good growth in soil containing mercury, even exceeding growth of plants
      cultivated in soil without mercury. The data obtained confirm the hypothesis that
      soil contamination by mercury alters community structure of root endophytic fungi
      in terms of composition, abundance and species richness. The inoculation of A.
      fluminensis with certain strains of stress tolerant endophytic fungi contribute
      to colonization and establishment of the host and may be used in processes that
      aim to improve phytoremediation of soils with toxic concentrations of mercury.

PMID- 28742847
TI  - Mining of high utility-probability sequential patterns from uncertain databases.
AB  - High-utility sequential pattern mining (HUSPM) has become an important issue in
      the field of data mining. Several HUSPM algorithms have been designed to mine
      high-utility sequential patterns (HUPSPs). They have been applied in several real
      life situations such as for consumer behavior analysis and event detection in
      sensor networks. Nonetheless, most studies on HUSPM have focused on mining HUPSPs
      in precise data. But in real-life, uncertainty is an important factor as data is
      collected using various types of sensors that are more or less accurate. Hence,
      data collected in a real-life database can be annotated with existing
      probabilities. This paper presents a novel pattern mining framework called high
      utility-probability sequential pattern mining (HUPSPM) for mining high utility
      probability sequential patterns (HUPSPs) in uncertain sequence databases. A
      baseline algorithm with three optional pruning strategies is presented to mine
      HUPSPs. Moroever, to speed up the mining process, a projection mechanism is
      designed to create a database projection for each processed sequence, which is
      smaller than the original database. Thus, the number of unpromising candidates
      can be greatly reduced, as well as the execution time for mining HUPSPs.
      Substantial experiments both on real-life and synthetic datasets show that the
      designed algorithm performs well in terms of runtime, number of candidates,
      memory usage, and scalability for different minimum utility and minimum
      probability thresholds.

PMID- 28742848
TI  - Indicators to measure risk of disaster associated with drought: Implications for
      the health sector.
AB  - INTRODUCTION: Brazil has a large semiarid region, which covers part of 9 states,
      over 20% of the 5565 municipalities in the country and at 22.5 million persons,
      12% of the country's population. This region experiences recurrent and extended
      droughts and is characterized by low economic development, scarcity of natural
      resources including water, and difficult agricultural and livestock production.
      Local governments and communities need easily obtainable tools to aid their
      decision making process in managing risks associated with drought. METHODS: To
      inform decision-making at the level of municipalities, we investigated factors
      contributing to the health risks of drought. We used education and poverty
      indicators to measure vulnerability, number of drought damage evaluations and
      historical drought occurrences as indicators of hazard, and access to water as an
      indicator of exposure, to derive a drought disaster risk index. RESULTS:
      Indicators such as access to piped water, illiteracy and poverty show marked
      differences in most states and, in nearly all states, the living conditions of
      communities in the semiarid region are worse than in the rest of each state.
      There are municipalities at high drought disaster risk in every state and there
      are a larger number of municipalities at higher risks from the center to the
      north of the semiarid region. CONCLUSIONS: Understanding local hazards, exposures
      and vulnerabilities provides the means to understand local communities' risks and
      develop interventions to reduce them. In addition, communities in these regions
      need to be empowered to add their traditional knowledge to scientific tools, and
      to identify the actions most relevant to their needs and realities.

PMID- 28742849
TI  - Joint action aesthetics.
AB  - Synchronized movement is a ubiquitous feature of dance and music performance.
      Much research into the evolutionary origins of these cultural practices has
      focused on why humans perform rather than watch or listen to dance and music. In
      this study, we show that movement synchrony among a group of performers predicts
      the aesthetic appreciation of live dance performances. We developed a
      choreography that continuously manipulated group synchronization using a defined
      movement vocabulary based on arm swinging, walking and running. The choreography
      was performed live to four audiences, as we continuously tracked the performers'
      movements, and the spectators' affective responses. We computed dynamic synchrony
      among performers using cross recurrence analysis of data from wrist
      accelerometers, and implicit measures of arousal from spectators' heart rates.
      Additionally, a subset of spectators provided continuous ratings of enjoyment and
      perceived synchrony using tablet computers. Granger causality analyses
      demonstrate predictive relationships between synchrony, enjoyment ratings and
      spectator arousal, if audiences form a collectively consistent positive or
      negative aesthetic evaluation. Controlling for the influence of overall movement
      acceleration and visual change, we show that dance communicates group
      coordination via coupled movement dynamics among a group of performers. Our
      findings are in line with an evolutionary function of dance-and perhaps all
      performing arts-in transmitting social signals between groups of people. Human
      movement is the common denominator of dance, music and theatre. Acknowledging the
      time-sensitive and immediate nature of the performer-spectator relationship, our
      study makes a significant step towards an aesthetics of joint actions in the
      performing arts.

PMID- 28742850
TI  - Genes, cells, and biobanks: Yes, there's still a consent problem.
AB  - From a research perspective, the interest in biobanking continues to intensify.
      Governments and industry have invested heavily in biobanks, as exemplified by
      initiatives like the United Kingdom Biobank and United States' Precision Medicine
      Initiative. But despite this enthusiasm, many profound legal and ethical
      challenges remain unresolved. Indeed, there continues to be disagreements about
      how best to obtain consent and the degree and nature of control that research
      participants retain over donated samples and health information. Emerging social
      trends-including concerns about commercialization and perceived rights of
      continuing control ("biorights")-seem likely to intensify these issues.

PMID- 28742851
TI  - Knowledge, attitude and practice for cervical cancer prevention and control among
      women of childbearing age in Hossana Town, Hadiya zone, Southern Ethiopia:
      Community-based cross-sectional study.
AB  - BACKGROUND: Cervical cancer is the second most common female cancer which
      Ethiopia put a strategic goal to reduce its incidence and mortality by 2020. Lack
      of knowledge and poor attitude towards the disease and risk factors can affect
      screening practice and development of preventive behavior for cervical cancer.
      The aim of this study was to assess knowledge, attitude, practices and factors
      for each domain for cervical cancer among women of child bearing age in Hossana
      town, Southern, Ethiopia. METHODS: Community based cross sectional study was
      carried out in June 2015. A total of 583 participants were selected using
      systematic random sampling technique. Pretested structured interviewer
      administered questionnaire was used to gather the data. Data were entered in to
      Epi Info software version 3.5.4 and exported to SPSS version 16 for descriptive
      and logistic regression analysis. RESULTS: Two hundred seventy (46.3%) of the
      respondents had poor comprehensive knowledge. Only 58 (9.9%) of participants had
      been screed for the cervical cancer before the survey. Two hundred three (34.8%)
      of participants had negative attitude towards selected proxy variables. Not
      having health seeking behavior for cervical cancer [AOR: 5.45, 95% CI: (1.18,
      30.58), P <0.031], had not ever received information about cervical cancer and
      its prevention [AOR: 2.63, 95%CI: (1.78,8.84), P < 0.018] and not actively
      seeking health information about cervical cancer [AOR: 6.25, (95%CI: (1.26,
      31.06) P < 0.025] were significantly associated factors with poor knowledge. Poor
      knowledge score was associated with poor attitude [AOR: 56.51, 95%CI: (23.76,
      134.37), P <0.001]. Had not ever received information about the disease from any
      source [AOR: 45.24, (95%CI: (11.47, 178.54), P <0.001] was significantly
      associated factor with not to be screened for the disease. CONCLUSION: This study
      highlighted the importance of awareness creation, increasing knowledge, promoting
      active searching for health information and experiences of receiving information
      from any information sources regarding cervical cancer. Therefore, it will be
      essential to integrate cervical cancer prevention strategies with other
      reproductive health services at all level of health care delivery system.

PMID- 28742852
TI  - In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes.
AB  - We report in vitro and in vivo anti-inflammatory activities of a series of
      copper(II)-lawsone complexes of the general composition [Cu(Law)2(LN)x(H2O)(2
      x)].yH2O; where HLaw = 2-hydroxy-1,4-naphthoquinone, x = 1 when LN = pyridine (1)
      and 2-aminopyridine (3) and x = 2 when LN = imidazole (2), 3-aminopyridine (4), 4
      aminopyridine (5), 3-hydroxypyridine (6), and 3,5-dimethylpyrazole (7). The
      compounds were thoroughly characterized by physical techniques, including single
      crystal X-ray analysis of complex 2. Some of the complexes showed the ability to
      suppress significantly the activation of nuclear factor kappaB (NF-kappaB) both
      by lipopolysaccharide (LPS) and TNF-alpha (complexes 3-7 at 100 nM level) in the
      similar manner as the reference drug prednisone (at 1 MUM level). On the other
      hand, all the complexes 1-7 decreased significantly the levels of the secreted
      TNF-alpha after the LPS activation of THP-1 cells, thus showing the anti
      inflammatory potential via both NF-kappaB moderation and by other mechanisms,
      such as influence on TNF-alpha transcription and/or translation and/or secretion.
      In addition, a strong intracellular pro-oxidative effect of all the complexes has
      been found at 100 nM dose in vitro. The ability to suppress the inflammatory
      response, caused by the subcutaneous application of lambda-carrageenan, has been
      determined by in vivo testing in hind-paw edema model on rats. The most active
      complexes 1-3 (applied in a dose corresponding to 40 MUmol Cu/kg), diminished the
      formation of edema simalarly as the reference drug indomethacine (applied in 10
      mg/kg dose). The overall effect of the complexes, dominantly 1-3, shows
      similarity to anti-inflammatory drug benoxaprofen, known to induce intracellular
      pro-oxidative effects.

PMID- 28742853
TI  - Leadership and management training as a catalyst to health system strengthening
      in low-income settings: Evidence from implementation of the Zambia Management and
      Leadership course for district health managers in Zambia.
AB  - BACKGROUND: Research has shown that the modes of leadership and management may
      influence health outcomes. However, majority of health leaders and managers in
      many low-income countries are promoted on account of clinical expertise. It has
      been recognised that these new managers are often ill-prepared for managing
      complex health systems. In response to this challenge, the Zambian Ministry of
      Health (MoH) has developed the Governance and Management Capacity Building (GMCB)
      Strategic Plan (2012-2016), whose overarching goal is to improve health sector
      governance and create an environment that is result-oriented, accountable and
      transparent. This led to the introduction of a new in-service leadership and
      management course, which has come to be known as the Zambia Management and
      Leadership Academy (ZMLA). This paper presents the results of an impact
      evaluation of the ZMLA programme conducted in 2014. METHODS: This was a cross
      sectional mixed method study. The study targeted health workers, stakeholders and
      course implementers. ZMLA trainees were targeted to gain perspectives on the
      extent to which the programme affected levels of self-confidence resulting from
      knowledge gained. Perspectives were sought from both ZMLA and non ZMLA trainees
      to measure changes in the work environment. Stakeholder perspectives were
      collected from trainers and key informants involved in providing ZMLA training.
      RESULTS: On average, knowledge levels increased by 38% after each workshop. A
      comparison of the average self-rated scores from 444 management and leadership
      survey responses before ZMLA and after ZMLA training showed a significant
      increase in the proportion of participants that felt adequately trained to
      undertake management and leadership, from 63% (before) to 99% (after) in phase 1
      and 43% (before) to 98% (after) in the phase II cohort. The calculated before and
      after percentage change for work environment themes ranged from 5.8% to 13.4%.
      Majority of respondents perceived improvements in the workplace environment,
      especially in handling human resource management matters. The smallest
      improvement was noted in ethics and accountability. Qualitative interviews showed
      improvements in the meeting culture and a greater appreciation for the importance
      of meetings. Shared vision, teamwork and coordination seemed to have improved
      more in work places where the overall manager had received ZMLA training.
      CONCLUSION: Leadership and management training will be a key ingredient in health
      system strengthening in low-income settings. The ZMLA model was found to be
      acceptable and effective in improving knowledge and skills for health system
      managers with minimal disruption to health services.

PMID- 28742854
TI  - Risk of exposure to potential vector mosquitoes for rural workers in Northern Lao
      PDR.
AB  - BACKGROUND: One major consequence of economic development in South-East Asia has
      been a rapid expansion of rubber plantations, in which outbreaks of dengue and
      malaria have occurred. Here we explored the difference in risk of exposure to
      potential dengue, Japanese encephalitis (JE), and malaria vectors between rubber
      workers and those engaged in traditional forest activities in northern Laos PDR.
      METHODOLOGY/PRINCIPAL FINDINGS: Adult mosquitoes were collected for nine months
      in secondary forests, mature and immature rubber plantations, and villages. Human
      behavior data were collected using rapid participatory rural appraisals and
      surveys. Exposure risk was assessed by combining vector and human behavior and
      calculating the basic reproduction number (R0) in different typologies. Compared
      to those that stayed in the village, the risk of dengue vector exposure was
      higher for those that visited the secondary forests during the day (odds ratio
      (OR) 36.0), for those living and working in rubber plantations (OR 16.2) and for
      those that tapped rubber (OR 3.2). Exposure to JE vectors was also higher in the
      forest (OR 1.4) and, similar when working (OR 1.0) and living in the plantations
      (OR 0.8). Exposure to malaria vectors was greater in the forest (OR 1.3), similar
      when working in the plantations (OR 0.9) and lower when living in the plantations
      (OR 0.6). R0 for dengue was >2.8 for all habitats surveyed, except villages where
      R0<=0.06. The main malaria vector in all habitats was Anopheles maculatus s.l. in
      the rainy season and An. minimus s.l. in the dry season.
      CONCLUSIONS/SIGNIFICANCE: The highest risk of exposure to vector mosquitoes
      occurred when people visit natural forests. However, since rubber workers spend
      long periods in the rubber plantations, their risk of exposure is increased
      greatly compared to those who temporarily enter natural forests or remain in the
      village. This study highlights the necessity of broadening mosquito control to
      include rubber plantations.

PMID- 28742855
TI  - Decreases in heart rate variability are associated with postoperative
      complications in hip fracture patients.
AB  - BACKGROUND: To explore relevant associations between deviations in linear and
      nonlinear heart rate variability (HRV) scores, and short-term morbidity and
      mortality in patients undergoing hip-surgery after a fracture. METHODS: 165
      patients with hip fractures being admitted for surgery at two hospitals were
      included in a prospective cohort study. A short-term ECG was recorded within 24
      hours of arrival. 15 patients had to be excluded due to insufficient quality of
      the ECG recordings. 150 patients were included in the final analysis. Linear
      parameters were calculated in time domain: standard deviation of NN intervals
      (SDNN), root mean square of successive differences (rMSSD); and frequency domain:
      Total Power (TP), High Frequency Power (HF), Low Frequency Power (LF), Very Low
      Frequency Power (VLF), and the ratio of LF/HF. Postoperative outcome was
      evaluated at the time of discharge. This included occurrence of pneumonia,
      overall infection rate, stroke, myocardial infarction, and all-cause mortality.
      RESULTS: Patients experiencing complications had significantly lower rMSSD (p =
      0.04), and TP (p = 0.03) preoperatively. Postoperative infections were predicted
      by decreased VLF preoperatively (p = 0.04). There was a significant association
      between pneumonia and LF/HF<1 (p = 0.03). The likelihood ratio to develop
      pneumonia when LF/HF < 1 was 6,1. CONCLUSION: HRV seems to reflect the general
      frailty of the patient with hip fracture and might be used to identify patients
      in need of increased surveillance or prophylactic treatment.

PMID- 28742856
TI  - Fit for genomic and proteomic purposes: Sampling the fitness of nucleic acid and
      protein derivatives from formalin fixed paraffin embedded tissue.
AB  - The demand for nucleic acid and protein derivatives from formalin-fixed paraffin
      embedded (FFPE) tissue has greatly increased due to advances in extraction and
      purification methods, making these derivatives available for numerous genomic and
      proteomic platforms. Previously, DNA, RNA, microRNA (miRNA), or protein derived
      from FFPE tissue blocks were considered "unfit" for such platforms, as the
      process of tissue immobilization by FFPE resulted in cross-linked, fragmented,
      and chemically modified macromolecules. We conducted a systematic examination of
      nucleic acids and proteins co-extracted from 118 FFPE blocks sampled from the
      AIDS and Cancer Specimen Resource (ACSR) at The George Washington University
      after stratification by storage duration and the three most common tumor tissue
      types at the ACSR (adenocarcinoma, squamous cell carcinoma, and papillary
      carcinoma). DNA, RNA, miRNA, and protein could be co-extracted from 98% of the
      FFPE blocks sampled, with DNA and miRNA "fit" for diverse genomic purposes
      including sequencing. While RNA was the most labile of the FFPE derivatives,
      especially when assessed by RNA integrity number (RIN), it was still "fit" for
      genomic methods that use smaller sequence lengths, e.g., quantitative PCR. While
      more than half of the protein derivatives were fit for proteomic purposes, our
      analyses indicated a significant interaction effect on the absorbance values for
      proteins derived from FFPE, implying that storage duration may affect protein
      derivatives differently by tumor tissue type. The mean absorbance value for
      proteins derived from more recently stored FFPE was greater than protein derived
      from older FFPE, with the exception of adenocarcinoma tissue. Finally, the
      fitness of one type of derivative was weakly associated with the fitness of
      derivatives co-extracted from the same FFPE block. The current study used several
      novel quality assurance approaches and metrics to show that archival FFPE tissue
      blocks are a valuable resource for contemporary genomic and proteomic platforms.

PMID- 28742857
TI  - DNA-immunisation with dengue virus E protein domains I/II, but not domain III,
      enhances Zika, West Nile and Yellow Fever virus infection.
AB  - Dengue virus (DENV), the causative agent of dengue disease, is among the most
      important mosquito-borne pathogens worldwide. DENV is composed of four closely
      related serotypes and belongs to the Flaviviridae family alongside other
      important arthropod-borne viral pathogens such as Zika virus (ZIKV), West Nile
      virus (WNV) and Yellow Fever virus (YFV). After infection, the antibody response
      is mostly directed to the viral E glycoprotein which is composed of three
      structural domains named DI, DII and DIII that share variable degrees of homology
      among different viruses. Recent evidence supports a close serological interaction
      between ZIKV and DENV. The possibility of worse clinical outcomes as a
      consequence of antibody-dependent enhancement of infection (ADE) due to cross
      reactive antibodies with poor neutralisation activity is a matter of concern. We
      tested polyclonal sera from groups of female Balb/C mice vaccinated with DNA
      constructs expressing DI/DII, DIII or the whole sE from different DENV serotypes
      and compared their activity in terms of cross-reactivity, neutralisation of virus
      infection and ADE. Our results indicate that the polyclonal antibody responses
      against the whole sE protein are highly cross-reactive with strong ADE and poor
      neutralisation activities due to DI/DII immunodominance. Conversely, anti-DIII
      polyclonal antibodies are type-specific, with no ADE towards ZIKV, WNV and YFV,
      and strong neutralisation activity restricted only to DENV.

PMID- 28742858
TI  - Reduction of endoplasmic reticulum- mitochondria interactions in beta cells from
      patients with type 2 diabetes.
AB  - Type 2 diabetes develops when beta cells are not able to fulfill insulin needs.
      The role of the endoplasmic reticulum-mitochondria junction in coordinating the
      functions of these two organelles throughout the natural history of type 2
      diabetes is determinant and may explain the alterations of insulin biosynthesis.
      Our goal was to study endoplasmic reticulum and mitochondrial interactions in
      human beta cells from organ donors with type 2 diabetes. Pancreas samples were
      obtained via the network for pancreatic organ donors with diabetes (nPOD) based
      on disease status with 12 subjects with type 2 diabetes and 9 non-diabetic
      controls. We examined pancreatic specimens by immunofluorescence, in situ
      hybridization and in situ proximity ligation assay and compared the results to an
      in vitro model of beta-cell dysfunction. Expression of proteins that enable
      tethering and exchanges between endoplasmic reticulum (ER) and mitochondria and
      quantification of interconnection through mitochondria associated membranes (MAM)
      was investigated. In beta cells from type 2 diabetic cases as compared to
      controls, there was a significant increase in reticular expression of inositol
      triphosphate receptor-2 (IP3R2) both at the protein and mRNA levels, no
      difference in mitochondrial transit peptide receptor TOM20 and mitofusin-2
      expressions, and a decrease in the expression of voltage-dependent anion channel
      1 (VDAC-1). The number of IP3R2-VDAC-1 complexes identified by in situ proximity
      ligation assay was significantly lower in diabetic islets and in beta cells of
      diabetics as compared to controls. Treatment of Min6-B1 cells with palmitate
      altered glucose-stimulated insulin secretion, increased ER stress and
      significantly reduced ER-mitochondrial interactions. We can conclude that
      specific changes in reticular and mitochondrial beta cell proteins characterize
      human type 2 diabetes with reduction in organelle interactions. This finding
      opens new targets of intervention.

PMID- 28742859
TI  - Whole blood microRNA expression may not be useful for screening non-small cell
      lung cancer.
AB  - At least seven studies have suggested that microRNA levels in whole blood can be
      diagnostic for lung cancer. We conducted a large bi-institutional study to
      validate this. Qiagen(r) PAXgeneTM Blood miRNA System was used to collect blood
      and extract RNA from it for 85 pathologic stage I-IV non-small cell lung cancer
      (NSCLC) cases and 76 clinically-relevant controls who had a benign pulmonary
      mass, or a high risk of developing lung cancer because of a history of cigarette
      smoking or age >60 years. Cases and controls were similar for age, gender, race,
      and blood hemoglobin and leukocyte but not platelet levels (0.23 and 0.26
      million/MUl, respectively; t test P = 0.01). Exiqon(r) MiRCURYTM microarrays were
      used to quantify microRNAs in RNA isolates. Quantification was also performed
      using TaqmanTM microRNA reverse transcription (RT)-PCR assays for five microRNAs
      whose lung cancer-diagnostic potential had been suggested in seven published
      studies. Of the 1,941 human mature microRNAs detectable with the microarray
      platform, 598 (31%) were identified as expressed and reliably quantified among
      the study's subjects. However, none of the microRNAs was differentially expressed
      between cases and controls (P >0.05 at false discovery rate <5% in test using
      empirical Bayes-moderated t statistics). In classification analyses with leave
      one-out internal cross-validation, cases and controls could be identified by
      microRNA expression with 47% and 50% accuracy with support vector machines and
      top-scoring pair methods, respectively. Cases and controls did not differ for RT
      PCR-based measurements of any of the five microRNAs whose biomarker potential had
      been suggested by seven previous studies. Additionally, no difference for
      microRNA expression was noticed in microarray-based microRNA profiles of whole
      blood of 12 stage IA-IIIB NSCLC cases before and three-four weeks after tumor
      resection. These findings show that whole blood microRNA expression profiles lack
      diagnostic value for high-risk screening of NSCLC, though such value may exist
      for selective sub-groups of NSCLC and control populations.

PMID- 28742860
TI  - Prognostic significance of microRNA-101 in solid tumor: A meta-analysis.
AB  - MicroRNA-101 has been reported as an important factor in carcinogenesis of
      several malignant tumors. However, its actual role in prognosis among solid
      malignancies remains unclear. Accordingly, we performed this meta-analysis aiming
      to identify prognostic significance of miR-101 in solid tumor. Pooled hazard
      ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or
      disease-free survival (DFS)/metastasis-free survival (MFS)/progression-free
      survival (PFS)/relapse-free survival (RFS)/time-to progression (TTP) were
      estimated with random effects or fixed effects models on the basis of
      heterogeneity. Subgroup analysis, sensitive analysis and meta-regression analysis
      were also conducted to clarify the possible confounding factors and investigate
      the source of heterogeneity. Publication bias was evaluated by using Begg's and
      Egger's tests. A total of 21 studies containing 3753 cases were selected into our
      quantitative analysis via electronic database search. A lower expression of miR
      101 was significantly associated with worse OS (HR = 0.66, 95%CI [0.52-0.85], P =
      0.001) and PFS (HR = 0.70, 95%CI [0.51-0.95], P = 0.023) in patients with solid
      tumor. The under-expression of miRNA-101 is a credible indicator of poorer
      prognosis in several of solid malignancies.

PMID- 28742861
TI  - Targeting the permeability barrier and peptidoglycan recycling pathways to disarm
      Pseudomonas aeruginosa against the innate immune system.
AB  - Antimicrobial resistance is a continuously increasing threat that severely
      compromises our antibiotic arsenal and causes thousands of deaths due to hospital
      acquired infections by pathogens such as Pseudomonas aeruginosa, situation
      further aggravated by the limited development of new antibiotics. Thus,
      alternative strategies such as those targeting bacterial resistance mechanisms,
      virulence or potentiating the activity of our immune system resources are
      urgently needed. We have recently shown that mutations simultaneously causing the
      peptidoglycan recycling blockage and the beta-lactamase AmpC overexpression
      impair the virulence of P.aeruginosa. These findings suggested that peptidoglycan
      metabolism might be a good target not only for fighting antibiotic resistance,
      but also for the attenuation of virulence and/or potentiation of our innate
      immune weapons. Here we analyzed the activity of the innate immune elements
      peptidoglycan recognition proteins (PGRPs) and lysozyme against P. aeruginosa. We
      show that while lysozyme and PGRPs have a very modest basal effect over P.
      aeruginosa, their bactericidal activity is dramatically increased in the presence
      of subinhibitory concentrations of the permeabilizing agent colistin. We also
      show that the P. aeruginosa lysozyme inhibitors seem to play a very residual
      protective role even in permeabilizing conditions. In contrast, we demonstrate
      that, once the permeability barrier is overpassed, the activity of lysozyme and
      PGRPs is dramatically enhanced when inhibiting key peptidoglycan recycling
      components (such as the 3 AmpDs, AmpG or NagZ), indicating a decisive protective
      role for cell-wall recycling and that direct peptidoglycan-binding supports, at
      least partially, the activity of these enzymes. Finally, we show that recycling
      blockade when occurring simultaneously with AmpC overexpression determines a
      further decrease in the resistance against PGRP2 and lysozyme, linked to
      quantitative changes in the cell-wall. Thus, our results help to delineate new
      strategies against P. aeruginosa infections, simultaneously targeting beta-lactam
      resistance, cell-wall metabolism and virulence, ultimately enhancing the activity
      of our innate immune weapons.

PMID- 28742862
TI  - Plio-Pleistocene phylogeography of the Southeast Asian Blue Panchax killifish,
      Aplocheilus panchax.
AB  - The complex climatic and geological history of Southeast Asia has shaped this
      region's high biodiversity. In particular, sea level fluctuations associated with
      repeated glacial cycles during the Pleistocene both facilitated, and limited,
      connectivity between populations. In this study, we used data from two
      mitochondrial and three anonymous nuclear markers to determine whether a
      fresh/brackish water killifish, Aplocheilus panchax, Hamilton, 1822, could be
      used to further understand how climatic oscillations and associated sea level
      fluctuations have shaped the distribution of biota within this region, and
      whether such patterns show evidence of isolation within palaeodrainage basins.
      Our analyses revealed three major mitochondrial clades within A. panchax. The
      basal divergence of A. panchax mitochondrial lineages was approximately 3.5 Ma,
      whilst the subsequent divergence timings of these clades occurred early
      Pleistocene (~2.6 Ma), proceeding through the Pleistocene. Continuous
      phylogeographic analysis showed a clear west-east dispersal followed by rapid
      radiation across Southeast Asia. Individuals from Krabi, just north of the
      Isthmus of Kra, were more closely related to the Indian lineages, providing
      further evidence for a freshwater faunal disjunction at the Isthmus of Kra
      biogeographic barrier. Our results suggest that Sulawesi, across the Wallace
      Line, was colonised relatively recently (~30 ka). Nuclear DNA is less
      geographically structured, although Mantel tests indicated that nuclear genetic
      distances were correlated with geographic proximity. Overall, these results imply
      that recent gene flow, as opposed to historical isolation, has been the key
      factor determining patterns of nuclear genetic variation in A. panchax, however,
      some evidence of historical isolation is retained within the mitochondrial
      genome. Our study further validates the existence of a major biogeographic
      boundary at the Kra Isthmus, and also demonstrates the use of widely distributed
      fresh/brackishwater species in phylogeographic studies, and their ability to
      disperse across major marine barriers in relatively recent time periods.

PMID- 28742863
TI  - Antibacterial activity of tannins isolated from Sapium baccatum extract and use
      for control of tomato bacterial wilt.
AB  - In the search for new antibacterial agents from natural sources, we revealed that
      a crude methanol extract of Sapium baccatum was highly active against Ralstonia
      solanacearum, a causal agent of a serious disease called bacterial wilt of
      tomato. The bioassay-guided fractionation of this extract resulted in the
      isolation of seven known active compounds, including gallic acid, methyl gallate,
      corilagin, tercatain, chebulagic acid, chebulinic acid, and quercetin 3-O-alpha-L
      arabinopyranoside. Their chemical structures were determined by electrospray
      ionization mass spectrometry and nuclear magnetic resonance spectroscopy. An in
      vitro antibacterial bioassay using a broth microdilution method revealed that,
      except for quercetin 3-O-alpha-L-arabinopyranoside (MIC = 250 MUg/mL), the
      isolated compounds exhibited strong antibacterial activity against R.
      solanacearum (MIC = 26-52 MUg/mL). Among the seven compounds, methyl gallate
      exhibited the strongest broad-spectrum activity against most of the plant
      pathogenic bacteria tested (MIC = 26-250 MUg/mL). In the in vivo experiments, the
      crude extract of S. baccatum at 2000 and 1000 MUg/mL reduced the development of
      tomato bacterial wilt by 83 and 63%, respectively, under greenhouse conditions
      after 14 days of infection. The results suggested that the extracts of S.
      baccatum or isolated tannins could be used as natural bactericides for the
      control of bacterial wilt of tomato.

PMID- 28742864
TI  - Limited grounding-line advance onto the West Antarctic continental shelf in the
      easternmost Amundsen Sea Embayment during the last glacial period.
AB  - Precise knowledge about the extent of the West Antarctic Ice Sheet (WAIS) at the
      Last Glacial Maximum (LGM; c. 26.5-19 cal. ka BP) is important in order to 1)
      improve paleo-ice sheet reconstructions, 2) provide a robust empirical framework
      for calibrating paleo-ice sheet models, and 3) locate potential shelf refugia for
      Antarctic benthos during the last glacial period. However, reliable
      reconstructions are still lacking for many WAIS sectors, particularly for key
      areas on the outer continental shelf, where the LGM-ice sheet is assumed to have
      terminated. In many areas of the outer continental shelf around Antarctica,
      direct geological data for the presence or absence of grounded ice during the LGM
      is lacking because of post-LGM iceberg scouring. This also applies to most of the
      outer continental shelf in the Amundsen Sea. Here we present detailed marine
      geophysical and new geological data documenting a sequence of glaciomarine
      sediments up to ~12 m thick within the deep outer portion of Abbot Trough, a
      palaeo-ice stream trough on the outer shelf of the Amundsen Sea Embayment. The
      upper 2-3 meters of this sediment drape contain calcareous foraminifera of
      Holocene and (pre-)LGM age and, in combination with palaeomagnetic age
      constraints, indicate that continuous glaciomarine deposition persisted here
      since well before the LGM, possibly even since the last interglacial period. Our
      data therefore indicate that the LGM grounding line, whose exact location was
      previously uncertain, did not reach the shelf edge everywhere in the Amundsen
      Sea. The LGM grounding line position coincides with the crest of a distinct
      grounding-zone wedge ~100 km inland from the continental shelf edge. Thus, an
      area of >=6000 km2 remained free of grounded ice through the last glacial cycle,
      requiring the LGM grounding line position to be re-located in this sector, and
      suggesting a new site at which Antarctic shelf benthos may have survived the last
      glacial period.

PMID- 28742865
TI  - A novel mitochondrial genome of Arborophila and new insight into Arborophila
      evolutionary history.
AB  - The lineage of the Bar-backed Partridge (Arborophila brunneopectus) was
      investigated to determine the phylogenetic relationships within Arborophila as
      the species is centrally distributed within an area covered by the distributions
      of 22 South-east Asian hill partridge species. The complete mitochondrial genome
      (mitogenome) of A. brunneopectus was determined and compared with four other hill
      partridge species mitogenomes. NADH subunit genes are radical in hill partridge
      mitogenomes and contain the most potential positive selective sites around where
      variable sites are abundant. Together with 44 other mitogenomes of closely
      related species, we reconstructed highly resolved phylogenetic trees using
      maximum likelihood (ML) and Bayesian inference (BI) analyses and calculated the
      divergence and dispersal history of Arborophila using combined datasets composed
      of their 13-protein coding sequences. Arborophila is reportedly be the oldest
      group in Phasianidae whose ancestors probably originated in Asia. A. rufipectus
      shares a closer relationship with A. ardens and A. brunneopectus compared to A.
      gingica and A. rufogularis, and such relationships were supported and profiled by
      NADH dehydrogenase subunit 5 (ND5). The intragenus divergence of all five
      Arborophila species occurred in the Miocene (16.84~5.69 Mya) when there were
      periods of climate cooling. We propose that these cooling events in the Miocene
      forced hill partridges from higher to lower altitudes, which led to geographic
      isolation and speciation. We demonstrated that the apparently deleterious +1
      frameshift mutation in NADH dehydrogenase subunit 3 (ND3) found in all
      Arborophila is an ancient trait that has been eliminated in some younger
      lineages, such as Passeriformes. It is unclear of the biological advantages of
      this elimination for the relevant taxa and this requires further investigation.

PMID- 28742866
TI  - Contribution of factor H-Binding protein sequence to the cross-reactivity of
      meningococcal native outer membrane vesicle vaccines with over-expressed fHbp
      variant group 1.
AB  - Factor H-binding protein (fHbp) is an important meningococcal vaccine antigen.
      Native outer membrane vesicles with over-expressed fHbp (NOMV OE fHbp) have been
      shown to induce antibodies with broader functional activity than recombinant fHbp
      (rfHbp). Improved understanding of this broad coverage would facilitate rational
      vaccine design. We performed a pair-wise analysis of 48 surface-exposed amino
      acids involved in interacting with factor H, among 383 fHbp variant group 1
      sequences. We generated isogenic NOMV-producing meningococcal strains from an
      African serogroup W isolate, each over-expressing one of four fHbp variant group
      1 sequences (ID 1, 5, 9, or 74), including those most common among invasive
      African meningococcal isolates. Mice were immunised with each NOMV, and sera
      tested for IgG levels against each of the rfHbp ID and for ability to kill a
      panel of heterologous meningococcal isolates. At the fH-binding site, ID pairs
      differed by a maximum of 13 (27%) amino acids. ID 9 shared an amino acid sequence
      common to 83 ID types. The selected ID types differed by up to 6 amino acids, in
      the fH-binding site. All NOMV and rfHbp induced high IgG levels against each
      rfHbp. Serum killing from mice immunised with rfHbp was generally less efficient
      and more restricted compared to NOMV, which induced antibodies that killed most
      meningococci tested, with decreased stringency for ID type differences. Breadth
      of killing was mostly due to anti-fHbp antibodies, with some restriction
      according to ID type sequence differences. Nevertheless, under our experimental
      conditions, no relationship between antibody cross-reactivity and variation fH
      binding site sequence was identified. NOMV over-expressing different fHbp IDs
      belonging to variant group 1 induce antibodies with fine specificities against
      fHbp, and ability to kill broadly meningococci expressing heterologous fHbp IDs.
      The work reinforces that meningococcal NOMV with OE fHbp is a promising vaccine
      strategy, and provides a basis for rational selection of antigen sequence types
      for over-expression on NOMV.

PMID- 28742867
TI  - Assessing unmet needs in patients with cancer: An investigation of differential
      item functioning of the Needs Evaluation Questionnaire across gender, age and
      phase of the disease.
AB  - OBJECTIVE: The main aim of this study was to provide evidence of the broad
      employability of the NEQ with patients of different gender and age with cancer in
      different phases of the disease and care process, using an Item Response Theory
      (IRT) approach and investigating Differential Item Functioning (DIF). METHODS:
      The NEQ was completed by 762 patients visiting, consecutively, outpatient clinics
      or admitted to oncology wards. Patients included in the study had different
      primary tumor sites and were in different phases of the disease and care process.
      The properties of the questionnaire were analyzed by applying IRT to test how
      well each item of the scale concurs in measuring unmet needs, how reliable the
      whole scale is, and whether the scale was metrically invariant across gender,
      age, and phase of the disease. RESULTS: Results showed that the NEQ performed
      well in measuring unmet needs and measurement equivalence of the scale across
      gender, age, and phase of the disease was verified. CONCLUSIONS: The current
      study supports the utility and broad employability of the NEQ, thus providing
      empirical evidence that it is psychometrically sound and metrically equivalent
      across different groups of cancer patients. As such, the scale could be an
      effective tool when planning psychosocial interventions to improve the care
      process and patients' quality of life.

PMID- 28742868
TI  - Combining ability of highland tropic adapted potato for tuber yield and yield
      components under drought.
AB  - Recurrent drought and late blight disease are the major factors limiting potato
      productivity in the northwest Ethiopian highlands. Incorporating drought
      tolerance and late blight resistance in the same genotypes will enable the
      development of cultivars with high and stable yield potential under erratic
      rainfall conditions. The objectives of this study were to assess combining
      ability effects and gene action for tuber yield and traits related to drought
      tolerance in the International Potato Centre's (CIP's) advanced clones from the
      late blight resistant breeding population B group 'B3C2' and to identify
      promising parents and families for cultivar development. Sixteen advanced clones
      from the late blight resistant breeding population were crossed in two sets using
      the North Carolina Design II. The resulting 32 families were evaluated together
      with five checks and 12 parental clones in a 7 x 7 lattice design with two water
      regimes and two replications. The experiment was carried out at Adet, in
      northwest Ethiopia under well-watered and water stressed conditions with terminal
      drought imposed from the tuber bulking stage. The results showed highly
      significant differences between families, checks, and parents for growth,
      physiological, and tuber yield related traits. Traits including marketable tuber
      yield, marketable tuber number, average tuber weight and groundcover were
      positively correlated with total tuber yield under both drought stressed and well
      watered conditions. Plant height was correlated with yield only under drought
      stressed condition. GCA was more important than SCA for total tuber yield,
      marketable tuber yield, average tuber weight, plant height, groundcover, and
      chlorophyll content under stress. This study identified the parents with best GCA
      and the combinations with best SCA effects, for both tuber yield and drought
      tolerance related traits. The new population is shown to be a valuable genetic
      resource for variety selection and improvement of potato's adaptation to the
      drought prone areas in northwest Ethiopia and similar environments.

PMID- 28742869
TI  - Ultrasound non-invasive measurement of intracranial pressure in neurointensive
      care: A prospective observational study.
AB  - BACKGROUND: The invasive nature of the current methods for monitoring of
      intracranial pressure (ICP) has prevented their use in many clinical situations.
      Several attempts have been made to develop methods to monitor ICP non-invasively.
      The aim of this study is to assess the relationship between ultrasound-based non
      invasive ICP (nICP) and invasive ICP measurement in neurocritical care patients.
      METHODS AND FINDINGS: This was a prospective, single-cohort observational study
      of patients admitted to a tertiary neurocritical care unit. Patients with brain
      injury requiring invasive ICP monitoring were considered for inclusion. nICP was
      assessed using optic nerve sheath diameter (ONSD), venous transcranial Doppler
      (vTCD) of straight sinus systolic flow velocity (FVsv), and methods derived from
      arterial transcranial Doppler (aTCD) on the middle cerebral artery (MCA): MCA
      pulsatility index (PIa) and an estimator based on diastolic flow velocity (FVd).
      A total of 445 ultrasound examinations from 64 patients performed from 1 January
      to 1 November 2016 were included. The median age of the patients was 53 years
      (range 37-64). Median Glasgow Coma Scale at admission was 7 (range 3-14), and
      median Glasgow Outcome Scale was 3 (range 1-5). The mortality rate was 20%. ONSD
      and FVsv demonstrated the strongest correlation with ICP (R = 0.76 for ONSD
      versus ICP; R = 0.72 for FVsv versus ICP), whereas PIa and the estimator based on
      FVd did not correlate with ICP significantly. Combining the 2 strongest nICP
      predictors (ONSD and FVsv) resulted in an even stronger correlation with ICP (R =
      0.80). The ability to detect intracranial hypertension (ICP >= 20 mm Hg) was
      highest for ONSD (area under the curve [AUC] 0.91, 95% CI 0.88-0.95). The
      combination of ONSD and FVsv methods showed a statistically significant
      improvement of AUC values compared with the ONSD method alone (0.93, 95% CI 0.90
      0.97, p = 0.01). Major limitations are the heterogeneity and small number of
      patients included in this study, the need for specialised training to perform and
      interpret the ultrasound tests, and the variability in performance among
      different ultrasound operators. CONCLUSIONS: Of the studied ultrasound nICP
      methods, ONSD is the best estimator of ICP. The novel combination of ONSD
      ultrasonography and vTCD of the straight sinus is a promising and easily
      available technique for identifying critically ill patients with intracranial
      hypertension.

PMID- 28742870
TI  - Factors contributing to food insecurity among women living with HIV in the
      Dominican Republic: A qualitative study.
AB  - BACKGROUND: Food insecurity contributes to poor health outcomes among people
      living with HIV. In Latin America and the Caribbean, structural factors such as
      poverty, stigma, and inequality disproportionately affect women and may fuel both
      the HIV epidemic and food insecurity. METHODS: We examined factors contributing
      to food insecurity among women living with HIV (WLHIV) in the Dominican Republic
      (DR). Data collection included in-depth, semi-structured interviews in 2013 with
      30 WLHIV with indications of food insecurity who resided in urban or peri-urban
      areas and were recruited from local HIV clinics. In-person interviews were
      conducted in Spanish. Transcripts were coded using content analysis methods and
      an inductive approach to identify principal and emergent themes. RESULTS:
      Respondents identified economic instability as the primary driver of food
      insecurity, precipitated by enacted stigma in the labor and social domains. Women
      described experiences of HIV-related labor discrimination in formal and informal
      sectors. Women commonly reported illegal HIV testing by employers, and subsequent
      dismissal if HIV-positive, especially in tourism and free trade zones. Enacted
      stigma in the social domain manifested as gossip and rejection by family,
      friends, and neighbors and physical, verbal, and sexual abuse by intimate
      partners, distancing women from sources of economic and food support. These
      experiences with discrimination and abuse contributed to internalized stigma
      among respondents who, as a result, were fearful and hesitant to disclose their
      HIV status; some participants reported leaving spouses and/or families, resulting
      in further isolation from economic resources, food and other support. A minority
      of participants described social support by friends, spouses, families and
      support groups, which helped to ameliorate food insecurity and emotional
      distress. CONCLUSIONS: Addressing food insecurity among WLHIV requires policy and
      programmatic interventions to enforce existing laws designed to protect the
      rights of people living with HIV, reduce HIV-related stigma, and improve gender
      equality.

PMID- 28742871
TI  - Comprehensive immune profiling reveals substantial immune system alterations in a
      subset of patients with amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a
      median lifespan of 2-3 years after diagnosis. There are few meaningful treatments
      that alter progression in this disease. Preclinical and clinical studies have
      demonstrated that neuroinflammation may play a key role in the progression rate
      of ALS. Despite this, there are no validated biomarkers of neuroinflammation for
      use in clinical practice or clinical trials. Biomarkers of neuroinflammation
      could improve patient management, provide new therapeutic targets, and possibly
      help stratify clinical trial selection and monitoring. However, attempts to
      identify a singular cause of neuroinflammation have not been successful. Here, we
      performed multi-parameter flow cytometry to comprehensively assess 116 leukocyte
      populations and phenotypes from lymphocytes, monocytes, and granulocytes in a
      cohort of 80 ALS patients. We identified 32 leukocyte phenotypes that were
      altered in ALS patients compared to age and gender matched healthy volunteers
      (HV) that included phenotypes of both inflammation and immune suppression.
      Unsupervised hierarchical clustering and principle component analysis of ALS and
      HV immunophenotypes revealed two distinct immune profiles of ALS patients. ALS
      patients were clustered into a profile distinct from HVs primarily due to
      differences in a multiple T cell phenotypes, CD3+CD56+ T cells and HLA-DR on
      monocytes. Patients clustered into an abnormal immune profile were younger, more
      likely to have a familial form of the disease, and survived longer than those
      patients who clustered similarly with healthy volunteers (344 weeks versus 184
      weeks; p = 0.012). The data set generated from this study establishes an
      extensive accounting of immunophenotypic changes readily suitable for biomarker
      validation studies. The extensive immune system changes measured in this study
      indicate that normal immune homeostatic mechanisms are disrupted in ALS patients,
      and that multiple immune states likely exist within a population of patients with
      ALS.

PMID- 28742872
TI  - The wheat WRKY transcription factors TaWRKY49 and TaWRKY62 confer differential
      high-temperature seedling-plant resistance to Puccinia striiformis f. sp.
      tritici.
AB  - WRKY transcription factors (TFs) play crucial roles in plant resistance responses
      to pathogens. Wheat stripe rust, caused by the fungal pathogen Puccinia
      striiformis f. sp. tritici (Pst), is a destructive disease of wheat (Triticum
      aestivum) worldwide. In this study, the two WRKY genes TaWRKY49 and TaWRKY62 were
      originally identified in association with high-temperature seedling-plant
      resistance to Pst (HTSP) resistance in wheat cultivar Xiaoyan 6 by RNA-seq.
      Interestingly, the expression levels of TaWRKY49 and TaWRKY62 were down- and up
      regulated, respectively, during HTSP resistance in response to Pst. Silencing of
      TaWRKY49 enhanced whereas silencing TaWRKY62 reduced HTSP resistance. The
      enhanced resistance observed on leaves following the silencing of TaWRKY49 was
      coupled with increased expression of salicylic acid (SA)- and jasmonic acid (JA)
      responsive genes TaPR1.1 and TaAOS, as well as reactive oxygen species (ROS)
      associated genes TaCAT and TaPOD; whereas the ethylene (ET)-responsive gene
      TaPIE1 was suppressed. The decreased resistance observed on leaves following
      TaWRKY62 silencing was associated with increased expression of TaPR1.1 and TaPOD,
      and suppression of TaAOS and TaPIE1. Furthermore, SA, ET, MeJA (methyl
      jasmonate), hydrogen peroxide (H2O2) and abscisic acid (ABA) treatments increased
      TaWRKY62 expression. On the other hand, MeJA did not affect the expression of
      TaWRKY49, and H2O2 reduced TaWRKY49 expression. In conclusion, TaWRKY49
      negatively regulates while TaWRKY62 positively regulates wheat HTSP resistance to
      Pst by differential regulation of SA-, JA-, ET and ROS-mediated signaling.

PMID- 28742873
TI  - Orienting towards social features in naturalistic scenes is reflexive.
AB  - Saliency-based models of visual attention postulate that, when a scene is freely
      viewed, attention is predominantly allocated to those elements that stand out in
      terms of their physical properties. However, eye-tracking studies have shown that
      saliency models fail to predict gaze behavior accurately when social information
      is included in an image. Notably, gaze pattern analyses revealed that depictions
      of human beings are heavily prioritized independent of their low-level physical
      saliency. What remains unknown, however, is whether the prioritization of such
      social features is a reflexive or a voluntary process. To investigate the early
      stages of social attention in more detail, participants viewed photographs of
      naturalistic scenes with and without social features (i.e., human heads or
      bodies) for 200 ms while their eye movements were being recorded. We observed
      significantly more first eye movements to regions containing social features than
      would be expected from a chance level distribution of saccades. Additionally, a
      generalized linear mixed model analysis revealed that the social content of a
      region better predicted first saccade direction than its saliency suggesting that
      social features partially override the impact of low-level physical saliency on
      gaze patterns. Given the brief image presentation time that precluded visual
      exploration, our results provide compelling evidence for a reflexive component in
      social attention. Moreover, the present study emphasizes the importance of
      considering social influences for a more coherent understanding of human
      attentional selection.

PMID- 28742874
TI  - The relationship between early and late event-related potentials and temperament
      in adolescents with and without ADHD.
AB  - Differences in emotional processing are prevalent in adolescents with attention
      deficit/hyperactivity disorder (ADHD) and are related to clinical impairment, but
      substantial heterogeneity exists. Within ADHD, some individuals experience
      difficulty with positive/approach emotions, negative/withdrawal emotions, or
      both. These problems may reflect differences in emotional reactivity, emotion
      regulation, or a combination, and the neurophysiological correlates remain
      unclear. Event-related potentials were collected from 109 adolescents (49 with
      ADHD) while they completed an emotional go/no-go task with three conditions:
      happy (positive/approach), fear (negative/withdrawal), and neutral. The P1 and
      N170 were used as a marker of early emotional processing and the P3b and late
      positive potential (LPP) were used as markers of later elaborative emotional
      processing. Emotional response style was assessed with parent and adolescent
      report on the Early Adolescent Temperament Questionnaire. There were no effects
      of emotion or group for the P1. Typically-developing adolescents exhibited a
      larger N170 to emotional vs. neutral faces while adolescents with ADHD showed the
      opposite pattern. All adolescents exhibited a larger P3b to fearful versus other
      faces and a larger LPP to emotional vs. non-emotional faces. Within the ADHD
      group, N170 responses to happy faces predicted parent ratings of
      positive/approach emotions. Findings highlight the importance of considering
      within-group heterogeneity when studying clinical populations and help clarify
      the time-locked neurophysiological correlates of emotion dysregulation.

PMID- 28742875
TI  - The significance of inadequate transcranial Doppler studies in children with
      sickle cell disease.
AB  - Sickle cell disease (SCD) is a common cause of cerebrovascular disease in
      childhood. Primary stroke prevention is effective using transcranial Doppler
      (TCD) scans to measure intracranial blood velocities, and regular blood
      transfusions or hydroxycarbamide when these are abnormal. Inadequate TCD scans
      occur when it is not possible to measure velocities in all the main arteries. We
      have investigated the prevalence and significance of this in a retrospective
      audit of 3915 TCD scans in 1191 children, performed between 2008 and 2015. 79%
      scans were normal, 6.4% conditional, 2.8% abnormal and 12% inadequate. 21.6% of
      1191 patients had an inadequate scan at least once. The median age of first
      inadequate scan was 3.3 years (0.7-19.4), with a U-shaped frequency distribution
      with age: 28% aged 2-3 years, 3.5% age 10 years, 25% age 16 years. In young
      children reduced compliance was the main reason for inadequate TCDs, whereas in
      older children it was due to a poor temporal ultrasound window. The prevalence of
      inadequate TCD was 8% in the main Vascular Laboratory at King's College Hospital
      and significantly higher at 16% in the outreach clinics (P<0.0001), probably due
      to the use of a portable ultrasound machine. Inadequate TCD scans were not
      associated with underlying cerebrovascular disease.

PMID- 28742876
TI  - Expression of uncharacterized male germ cell-specific genes and discovery of
      novel sperm-tail proteins in mice.
AB  - The identification and characterization of germ cell-specific genes are essential
      if we hope to comprehensively understand the mechanisms of spermatogenesis and
      fertilization. Here, we searched the mouse UniGene databases and identified 13
      novel genes as being putatively testis-specific or -predominant. Our in silico
      and in vitro analyses revealed that the expressions of these genes are testis-
      and germ cell-specific, and that they are regulated in a stage-specific manner
      during spermatogenesis. We generated antibodies against the proteins encoded by
      seven of the genes to facilitate their characterization in male germ cells.
      Immunoblotting and immunofluorescence analyses revealed that one of these
      proteins was expressed only in testicular germ cells, three were expressed in
      both testicular germ cells and testicular sperm, and the remaining three were
      expressed in sperm of the testicular stages and in mature sperm from the
      epididymis. Further analysis of the latter three proteins showed that they were
      all associated with cytoskeletal structures in the sperm flagellum. Among them,
      MORN5, which is predicted to contain three MORN motifs, is conserved between
      mouse and human sperm. In conclusion, we herein identify 13 authentic genes with
      male germ cell-specific expression, and provide comprehensive information about
      these genes and their encoded products. Our finding will facilitate future
      investigations into the functional roles of these novel genes in spermatogenesis
      and sperm functions.

PMID- 28742877
TI  - Predictors of mortality in autoimmune disease patients with concurrent
      cytomegalovirus infections detected by quantitative real-time PCR.
AB  - OBJECTIVE: Cytomegaloviruses (CMV) can have a significant impact on the prognosis
      of immunocompromised patients. Unlike in the transplantation and AIDS fields,
      only a few studies on CMV infections have been published in the field of
      autoimmunity. In this study, we examined the clinical outcomes of CMV infections
      in patients with autoimmune diseases at a single tertiary medical institution.
      METHODS: A retrospective study was performed to identify the mortality risk
      factors associated with CMV infections in patients with autoimmune diseases. We
      reviewed the medical records of patients with autoimmune diseases who were
      diagnosed with CMV infections using real-time quantitative polymerase chain
      reaction between December 2005 and March 2016. Clinical and laboratory parameters
      as well as treatment outcomes were analyzed. RESULTS: Seventy-three CMV infected
      patients were separated into survivors and non-survivors. Non-survivors had
      significantly higher median CMV-DNA copy numbers than survivors (95,500 vs 6,700
      copies/mL, p = 0.005) and demonstrated significantly more frequent incidents of
      CMV pneumonitis (69.2 vs 36.2%, p = 0.007). After adjusting for multiple
      confounding covariates, the log CMV-DNA copies/mL (hazard ratio, 1.48; 95%
      confidence interval, 1.14-1.92; p = 0.003) and the presence of concurrent
      infections (hazard ratio, 22.00; 95% confidence interval, 2.75-175.97, p = 0.004)
      were identified as independent mortality risk factors. Furthermore, patients with
      high CMV copy numbers (> 60,000 copies/mL) had higher in-hospital mortality than
      those with low CMV copy numbers (p < 0.05). CONCLUSIONS: CMV-DNA copy numbers and
      concurrent infections are predictors of in-hospital mortality in CMV-infected
      patients with autoimmune diseases. Therefore, serial measurements of CMV-DNA copy
      numbers and close observation for signs of other infections are recommended for
      patients with autoimmune diseases who have concurrent CMV infection.

PMID- 28742878
TI  - Assessment of the effect of Enteromorpha prolifera on bacterial community
      structures in aquaculture environment.
AB  - In recent years, Enteromorpha prolifera blooms had serious impacts on costal
      environments and fisheries in China. Nevertheless, the effects of E. prolifera on
      microbial ecology remain unknown. In this study, for the first time, an Illumina
      sequencing analysis was used to investigate bacterial communities in source
      water, aquaculture ponds with E. prolifera, and an aquaculture pond in which E.
      prolifera -free. Principal coordinate and phylogenic analyses revealed obvious
      differences among the bacterial communities in the pond water with and without E.
      prolifera. Abundant bacterial taxa in the E. prolifera-containing pond were
      generally absent from the pond without E. prolifera. Interestingly, pond water
      with E. prolifera was dominated by Actinomycetales (> 50%), as well as by
      anaerobic bacteria in the underlying sediment (Desulfobacterales and
      Desulfuromonadales (> 20%). Pond water in which E. prolifera-free was dominated
      by Rhodobacterales (58.19%), as well as aerobic and facultative anaerobic
      bacteria in the sediment. In addition, the ecological functions of other dominant
      bacteria, such as Candidatus Aquiluna, Microcella spp., and Marivita spp., should
      be studied in depth. Overall, massive growth of E. prolifera will have serious
      effects on bacterial communities, and, thus, it will have an important impact on
      the environment. The novel findings in this study will be valuable for
      understanding green tides.

PMID- 28742879
TI  - Epidemiological investigations of the introduction of porcine reproductive and
      respiratory syndrome virus in Chile, 2013-2015.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is endemic in most pork
      producing countries. In Chile, eradication of PRRS virus (PRRSV) was successfully
      achieved in 2009 as a result of the combined efforts of producers and the animal
      health authorities. In October 2013, after several years without detecting PRRSV
      under surveillance activities, suspected cases were confirmed on a commercial
      swine farm. Here, we describe the PRRS epidemic in Chile between October 2013 and
      April 2015, and we studied the origins and spread of PRRSV throughout the country
      using official surveillance data and Bayesian phylogenetic analysis. Our results
      indicate that the outbreaks were caused by a PRRSV closely related to viruses
      present in swine farms in North America, and different from the strain that
      circulated in the country before 2009. Using divergence time estimation analysis,
      we found that the 2013-2015 PRRSV may have been circulating in Chile for at least
      one month before the first detection. A single strain of PRRSV spread into a
      limited number of commercial and backyard swine farms. New infections in
      commercial systems have not been reported since October 2014, and eradication is
      underway by clearing the disease from the few commercial and backyard farms that
      remain positive. This is one of the few documented experiences of PRRSV
      introduction into a disease-free country.

PMID- 28742880
TI  - Same-day HIV testing with initiation of antiretroviral therapy versus standard
      care for persons living with HIV: A randomized unblinded trial.
AB  - BACKGROUND: Attrition during the period from HIV testing to antiretroviral
      therapy (ART) initiation is high worldwide. We assessed whether same-day HIV
      testing and ART initiation improves retention and virologic suppression. METHODS
      AND FINDINGS: We conducted an unblinded, randomized trial of standard ART
      initiation versus same-day HIV testing and ART initiation among eligible adults
      >=18 years old with World Health Organization Stage 1 or 2 disease and CD4 count
      <=500 cells/mm3. The study was conducted among outpatients at the Haitian Group
      for the Study of Kaposi's Sarcoma and Opportunistic infections (GHESKIO) Clinic
      in Port-au-Prince, Haiti. Participants were randomly assigned (1:1) to standard
      ART initiation or same-day HIV testing and ART initiation. The standard group
      initiated ART 3 weeks after HIV testing, and the same-day group initiated ART on
      the day of testing. The primary study endpoint was retention in care 12 months
      after HIV testing with HIV-1 RNA <50 copies/ml. We assessed the impact of
      treatment arm with a modified intention-to-treat analysis, using multivariable
      logistic regression controlling for potential confounders. Between August 2013
      and October 2015, 762 participants were enrolled; 59 participants transferred to
      other clinics during the study period, and were excluded as per protocol, leaving
      356 in the standard and 347 in the same-day ART groups. In the standard ART
      group, 156 (44%) participants were retained in care with 12-month HIV-1 RNA <50
      copies, and 184 (52%) had <1,000 copies/ml; 20 participants (6%) died. In the
      same-day ART group, 184 (53%) participants were retained with HIV-1 RNA <50
      copies/ml, and 212 (61%) had <1,000 copies/ml; 10 (3%) participants died. The
      unadjusted risk ratio (RR) of being retained at 12 months with HIV-1 RNA <50
      copies/ml was 1.21 (95% CI: 1.04, 1.38; p = 0.015) for the same-day ART group
      compared to the standard ART group, and the unadjusted RR for being retained with
      HIV-1 RNA <1,000 copies was 1.18 (95% CI: 1.04, 1.31; p = 0.012). The main
      limitation of this study is that it was conducted at a single urban clinic, and
      the generalizability to other settings is uncertain. CONCLUSIONS: Same-day HIV
      testing and ART initiation is feasible and beneficial in this setting, as it
      improves retention in care with virologic suppression among patients with early
      clinical HIV disease. TRIAL REGISTRATION: This study is registered with
      ClinicalTrials.gov number NCT01900080.

PMID- 28742881
TI  - Epiphytes in wooded pastures: Isolation matters for lichen but not for bryophyte
      species richness.
AB  - Sylvo-pastoral systems are species-rich man-made landscapes that are currently
      often severely threatened by abandonment or management intensification. At low
      tree densities, single trees in these systems represent habitat islands for
      epiphytic cryptogams. Here, we focused on sycamore maple (Acer pseudoplatanus)
      wooded pastures in the northern European Alps. We assessed per tree species
      richness of bryophytes and lichens on 90 sycamore maple trees distributed across
      six study sites. We analysed the effects of a range of explanatory variables
      (tree characteristics, environmental variables and isolation measures) on the
      richness of epiphytic bryophytes and lichens and various functional subgroups
      (based on diaspore size, habitat preference and red list status). Furthermore, we
      estimated the effect of these variables on the occurrence of two specific
      bryophyte species (Tayloria rudolphiana, Orthotrichum rogeri) and one lichen
      species (Lobaria pulmonaria) of major conservation concern. Bryophytes and
      lichens, as well as their subgroups, were differently and sometimes contrastingly
      affected by the variables considered: tree diameter at breast height had no
      significant effect on bryophytes but negatively affected many lichen groups; tree
      phenological age positively affected red-listed lichens but not red-listed
      bryophytes; increasing isolation from neighbouring trees negatively affected
      lichens but not bryophytes. However, the high-priority bryophyte species T.
      rudolphiana was also negatively affected by increased isolation at small spatial
      scales. Orthotrichum rogeri was more frequent on young trees and L. pulmonaria
      was more frequent on trees with thin stems and large crowns. The results indicate
      that local dispersal is important for lichens, whereas long distance dispersal
      seems to be more important for colonisation by bryophytes. Furthermore, our study
      highlights that different conservation measures need to be taken depending on the
      taxonomic and functional species group or the individual species that is
      addressed. In practice, for the conservation of a high overall richness in sylvo
      pastoral systems, it is crucial to sustain not only old and large trees but
      rather a wide range of tree sizes and ages.

PMID- 28742882
TI  - T cell-intrinsic TLR2 stimulation promotes IL-10 expression and suppressive
      activity by CD45RbHi T cells.
AB  - While Toll-like receptors (TLRs) represent one of the best characterized innate
      immune pathways, evidence suggests that TLRs are not restricted to innate
      leukocytes and some epithelial cells, but are also expressed in T cells.
      Specifically, published evidence focusing on FoxP3+ regulatory T cells
      demonstrate that they express functional TLR2, which is already known among the
      TLR family for its association with immune suppression; however, little is known
      about the relationship between T cell-intrinsic TLR2 binding and cytokine
      production, T cell differentiation, or T cell receptor (TCR) stimulation. Here,
      we demonstrate that TCR and TLR2 co-stimulation provides a T cell-intrinsic
      signal which generates a dramatic, synergistic cytokine response dominated by IL
      10. Importantly, the response was not seen in either CD4+CD25+ or CD4+FoxP3+
      Tregs, yet resulted in the expansion of a suppressive CD4+CD25+CD62L
      CD44+CD45Rbhi effector/memory T cell subset not typically associated with immune
      inhibition. This study reveals the striking ability of a prototypical innate
      immune receptor to trigger a potent and suppressive IL-10 response in
      effector/memory T cells, supporting the notion that TLR2 is a co-regulatory
      receptor on T cells.

PMID- 28742883
TI  - Effects of oral florfenicol and azithromycin on gut microbiota and adipogenesis
      in mice.
AB  - Certain antibiotics detected in urine are associated with childhood obesity. In
      the current experimental study, we investigated two representative antibiotics
      detected in urine, florfenicol and azithromycin, for their early effects on
      adipogenesis, gut microbiota, short-chain fatty acids (SCFAs), and bile acids in
      mice. Thirty C57BL/6 mice aged four weeks were randomly divided into three groups
      (florfenicol, azithromycin and control). The two experimental groups were
      administered florfenicol or azithromycin at 5 mg/kg/day for four weeks. Body
      weight was measured weekly. The composition of the gut microbiota, body fat,
      SCFAs, and bile acids in colon contents were measured at the end of the
      experiment. The composition of the gut microbiota was determined by sequencing
      the bacterial 16S rRNA gene. The concentration of SCFAs and bile acids was
      determined using gas chromatography and liquid chromatography coupled to tandem
      mass spectrometry, respectively. The composition of the gut microbiota indicated
      that the two antibiotics altered the gut microbiota composition and decreased its
      richness and diversity. At the phylum level, the ratio of
      Firmicutes/Bacteroidetes increased significantly in the antibiotic groups. At the
      genus level, there were declines in Christensenella, Gordonibacter and
      Anaerotruncus in the florfenicol group, in Lactobacillus in the azithromycin
      group, and in Alistipes, Desulfovibrio, Parasutterella and Rikenella in both the
      antibiotic groups. The decrease in Rikenella in the azithromycin group was
      particularly noticeable. The concentration of SCFAs and secondary bile acids
      decreased in the colon, but the concentration of primary bile acids increased.
      These findings indicated that florfenicol and azithromycin increased adipogenesis
      and altered gut microbiota composition, SCFA production, and bile acid
      metabolism, suggesting that exposure to antibiotics might be one risk factor for
      childhood obesity. More studies are needed to investigate the specific
      mechanisms.

PMID- 28742884
TI  - Reduced expression of E-cadherin and increased sialylation level in clear cell
      renal cell carcinoma.
AB  - Cancer cells are characterized by an aberrant increase in protein N-glycosylation
      and by disruption of E-cadherin-mediated adherens junctions. However, the
      relationship between alterations in N-glycosylation process and loss of E
      cadherin adhesion in cancer remains unclear. The mechanisms of altered expression
      of adhesive glycoproteins in cancer cells have not been fully elucidated. Thus,
      the aim of this study was to examine the expression of E-cadherin and sialyl
      Lewisa/x, NeuAcalpha2-3Gal, NeuAcalpha2-6Gal/GalNAc structures in the normal
      renal tissue and intermediate and cancerous tissues from patients with clear cell
      RCC. Moreover, we attempted to correlate the E-cadherin expression with some
      specific sugar residues of renal cancer tissue glycoproteins. The expression of E
      cadherin was analysed using ELISA test and immunoblotting. Oligosaccharide
      structures and sialylation level were detected with ELISA test using specific
      biotinylated lectins or antibodies. A significant decrease of E-cadherin
      expression as well as a significant increase in sialylated oligosaccharides level
      in intermediate zone and renal cancer tissue in comparison to normal renal tissue
      are reported. Significant decrease in expression of cadherins and increase in
      sialylation of oligosaccharide structures in renal cancer tissue in comparison to
      normal renal tissue, and in renal cancer tissue in comparison to intermediate
      zone of renal tissue, are important for the future research concerning detection
      and quantification of cadherins and sialylated oligosaccharide structures in
      urine and cells of urinary sediment as possible non-invasive marker of early RCC.

PMID- 28742885
TI  - Epistaxis, Ecchymoses, and an Abnormal White Blood Cell Count.

PMID- 28742886
TI  - Metanephrines for Evaluating Palpitations and Flushing.

PMID- 28742887
TI  - Practical Improvements for Medical Device Evaluation.

PMID- 28742888
TI  - Targeted Temperature Management After Cardiac Arrest: Finding the Right Dose for
      Critical Care Interventions.

PMID- 28742889
TI  - Advances and Gaps in Understanding Chronic Traumatic Encephalopathy: From
      Pugilists to American Football Players.

PMID- 28742890
TI  - Interventions to Improve Infant Safe Sleep Practices.

PMID- 28742891
TI  - Chikungunya Vaccine Trials Begin.

PMID- 28742892
TI  - Cancer Project Speeding Along.

PMID- 28742893
TI  - New Medical Officer at Indian Health Service.

PMID- 28742895
TI  - Cascade Screening for Familial Hypercholesterolemia and the Use of Genetic
      Testing.

PMID- 28742896
TI  - Why Is US Maternal Mortality Rising?

PMID- 28742897
TI  - Domestic Correspondence: Laboratory Work in Medical Schools.

PMID- 28742898
TI  - Association of the Priority Review Voucher With Neglected Tropical Disease Drug
      and Vaccine Development.

PMID- 28742899
TI  - Nonclinical Factors Affecting Shared Decision Making.

PMID- 28742900
TI  - Deep Brain Stimulation for Obsessive-Compulsive Disorder.

PMID- 28742901
TI  - Increases in Thyroid Cancer Incidence and Mortality.

PMID- 28742902
TI  - Nonclinical Factors Affecting Shared Decision Making-Reply.

PMID- 28742903
TI  - Deep Brain Stimulation for Obsessive-Compulsive Disorder-Reply.

PMID- 28742904
TI  - Increases in Thyroid Cancer Incidence and Mortality-Reply.

PMID- 28742905
TI  - Fewer Seizures With Cannabidiol in Catastrophic Epilepsy.

PMID- 28742907
TI  - Combination Therapy Shrinks Melanoma Brain Metastases.

PMID- 28742906
TI  - Parent-Based Therapy Helps Children Lose Weight.

PMID- 28742908
TI  - Dual Strategy Increases Colorectal Cancer Screening.

PMID- 28742909
TI  - Blended CBT Controls Anxiety in Cancer Survivors.

PMID- 28742910
TI  - Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of
      American Football.
AB  - Importance: Players of American football may be at increased risk of long-term
      neurological conditions, particularly chronic traumatic encephalopathy (CTE).
      Objective: To determine the neuropathological and clinical features of deceased
      football players with CTE. Design, Setting, and Participants: Case series of 202
      football players whose brains were donated for research. Neuropathological
      evaluations and retrospective telephone clinical assessments (including head
      trauma history) with informants were performed blinded. Online questionnaires
      ascertained athletic and military history. Exposures: Participation in American
      football at any level of play. Main Outcomes and Measures: Neuropathological
      diagnoses of neurodegenerative diseases, including CTE, based on defined
      diagnostic criteria; CTE neuropathological severity (stages I to IV or
      dichotomized into mild [stages I and II] and severe [stages III and IV]);
      informant-reported athletic history and, for players who died in 2014 or later,
      clinical presentation, including behavior, mood, and cognitive symptoms and
      dementia. Results: Among 202 deceased former football players (median age at
      death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically
      diagnosed in 177 players (87%; median age at death, 67 years [interquartile
      range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]),
      including 0 of 2 pre-high school, 3 of 14 high school (21%), 48 of 53 college
      (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and
      110 of 111 National Football League (99%) players. Neuropathological severity of
      CTE was distributed across the highest level of play, with all 3 former high
      school players having mild pathology and the majority of former college (27
      [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having
      severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had
      behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%)
      had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%)
      had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71
      (85%) had signs of dementia. Conclusions and Relevance: In a convenience sample
      of deceased football players who donated their brains for research, a high
      proportion had neuropathological evidence of CTE, suggesting that CTE may be
      related to prior participation in football.

PMID- 28742911
TI  - Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After
      Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.
AB  - Importance: International resuscitation guidelines recommend targeted temperature
      management (TTM) at 33 degrees C to 36 degrees C in unconscious patients with out
      of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM
      is uncertain. Objective: To determine whether TTM at 33 degrees C for 48 hours
      results in better neurologic outcomes compared with currently recommended,
      standard, 24-hour TTM. Design, Setting, and Participants: This was an
      international, investigator-initiated, blinded-outcome-assessor, parallel,
      pragmatic, multicenter, randomized clinical superiority trial in 10 intensive
      care units (ICUs) at 10 university hospitals in 6 European countries. Three
      hundred fifty-five adult, unconscious patients with out-of-hospital cardiac
      arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow
      up on December 27, 2016. Interventions: Patients were randomized to TTM (33 +/- 1
      degrees C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual
      rewarming of 0.5 degrees C per hour until reaching 37 degrees C. Main Outcomes
      and Measures: The primary outcome was 6-month neurologic outcome, with a Cerebral
      Performance Categories (CPC) score of 1 or 2 used to define favorable outcome.
      Secondary outcomes included 6-month mortality, including time to death, the
      occurrence of adverse events, and intensive care unit resource use. Results: In
      355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%)
      completed the trial. Of these patients, 69% (120/175) in the 48-hour group had a
      favorable outcome at 6 months compared with 64% (112/176) in the 24-hour group
      (difference, 4.9%; 95% CI, -5% to 14.8%; relative risk [RR], 1.08; 95% CI, 0.93
      1.25; P = .33). Six-month mortality was 27% (48/175) in the 48-hour group and 34%
      (60/177) in the 24-hour group (difference, -6.5%; 95% CI, -16.1% to 3.1%; RR,
      0.81; 95% CI, 0.59-1.11; P = .19). There was no significant difference in the
      time to mortality between the 48-hour group and the 24-hour group (hazard ratio,
      0.79; 95% CI, 0.54-1.15; P = .22). Adverse events were more common in the 48-hour
      group (97%) than in the 24-hour group (91%) (difference, 5.6%; 95% CI, 0.6%
      10.6%; RR, 1.06; 95% CI, 1.01-1.12; P = .04). The median length of intensive care
      unit stay (151 vs 117 hours; P < .001), but not hospital stay (11 vs 12 days; P =
      .50), was longer in the 48-hour group than in the 24-hour group. Conclusions and
      Relevance: In unconscious survivors from out-of-hospital cardiac arrest admitted
      to the ICU, targeted temperature management at 33 degrees C for 48 hours did not
      significantly improve 6-month neurologic outcome compared with targeted
      temperature management at 33 degrees C for 24 hours. However, the study may have
      had limited power to detect clinically important differences, and further
      research may be warranted. Trial Registration: clinicaltrials.gov Identifier:
      NCT01689077.

PMID- 28742912
TI  - Association of Genetic Variants Related to Serum Calcium Levels With Coronary
      Artery Disease and Myocardial Infarction.
AB  - Importance: Serum calcium has been associated with cardiovascular disease in
      observational studies and evidence from randomized clinical trials indicates that
      calcium supplementation, which raises serum calcium levels, may increase the risk
      of cardiovascular events, particularly myocardial infarction. Objective: To
      evaluate the potential causal association between genetic variants related to
      elevated serum calcium levels and risk of coronary artery disease (CAD) and
      myocardial infarction using mendelian randomization. Design, Setting, and
      Participants: The analyses were performed using summary statistics obtained for
      single-nucleotide polymorphisms (SNPs) identified from a genome-wide association
      meta-analysis of serum calcium levels (N = up to 61 079 individuals) and from the
      Coronary Artery Disease Genome-wide Replication and Meta-analysis Plus the
      Coronary Artery Disease Genetics (CardiogramplusC4D) consortium's 1000 genomes
      based genome-wide association meta-analysis (N = up to 184 305 individuals) that
      included cases (individuals with CAD and myocardial infarction) and noncases,
      with baseline data collected from 1948 and populations derived from across the
      globe. The association of each SNP with CAD and myocardial infarction was
      weighted by its association with serum calcium, and estimates were combined using
      an inverse-variance weighted meta-analysis. Exposures: Genetic risk score based
      on genetic variants related to elevated serum calcium levels. Main Outcomes and
      Measures: Co-primary outcomes were the odds of CAD and myocardial infarction.
      Results: Among the mendelian randomized analytic sample of 184 305 individuals
      (60 801 CAD cases [approximately 70% with myocardial infarction] and 123 504
      noncases), the 6 SNPs related to serum calcium levels and without pleiotropic
      associations with potential confounders were estimated to explain about 0.8% of
      the variation in serum calcium levels. In the inverse-variance weighted meta
      analysis (combining the estimates of the 6 SNPs), the odds ratios per 0.5-mg/dL
      increase (about 1 SD) in genetically predicted serum calcium levels were 1.25
      (95% CI, 1.08-1.45; P = .003) for CAD and 1.24 (95% CI, 1.05-1.46; P = .009) for
      myocardial infarction. Conclusions and Relevance: A genetic predisposition to
      higher serum calcium levels was associated with increased risk of CAD and
      myocardial infarction. Whether the risk of CAD associated with lifelong genetic
      exposure to increased serum calcium levels can be translated to a risk associated
      with short-term to medium-term calcium supplementation is unknown.

PMID- 28742914
TI  - Plantar Fasciitis.

PMID- 28742913
TI  - The Effect of Nursing Quality Improvement and Mobile Health Interventions on
      Infant Sleep Practices: A Randomized Clinical Trial.
AB  - Importance: Inadequate adherence to recommendations known to reduce the risk of
      sudden unexpected infant death has contributed to a slowing in the decline of
      these deaths. Objective: To assess the effectiveness of 2 interventions
      separately and combined to promote infant safe sleep practices compared with
      control interventions. Design, Setting, and Participants: Four-group cluster
      randomized clinical trial of mothers of healthy term newborns who were recruited
      between March 2015 and May 2016 at 16 US hospitals with more than 100 births
      annually. Data collection ended in October 2016. Interventions: All participants
      were beneficiaries of a nursing quality improvement campaign in infant safe sleep
      practices (intervention) or breastfeeding (control), and then received a 60-day
      mobile health program, in which mothers received frequent emails or text messages
      containing short videos with educational content about infant safe sleep
      practices (intervention) or breastfeeding (control) and queries about infant care
      practices. Main Outcomes and Measures: The primary outcome was maternal self
      reported adherence to 4 infant safe sleep practices of sleep position (supine),
      sleep location (room sharing without bed sharing), soft bedding use (none), and
      pacifier use (any); data were collected by maternal survey when the infant was
      aged 60 to 240 days. Results: Of the 1600 mothers who were randomized to 1 of 4
      groups (400 per group), 1263 completed the survey (78.9%). The mean (SD) maternal
      age was 28.1 years (5.8 years) and 32.8% of respondents were non-Hispanic white,
      32.3% Hispanic, 27.2% non-Hispanic black, and 7.7% other race/ethnicity. The mean
      (SD) infant age was 11.2 weeks (4.4 weeks) and 51.2% were female. In the adjusted
      analyses, mothers receiving the safe sleep mobile health intervention had higher
      prevalence of placing their infants supine compared with mothers receiving the
      control mobile health intervention (89.1% vs 80.2%, respectively; adjusted risk
      difference, 8.9% [95% CI, 5.3%-11.7%]), room sharing without bed sharing (82.8%
      vs 70.4%; adjusted risk difference, 12.4% [95% CI, 9.3%-15.1%]), no soft bedding
      use (79.4% vs 67.6%; adjusted risk difference, 11.8% [95% CI, 8.1%-15.2%]), and
      any pacifier use (68.5% vs 59.8%; adjusted risk difference, 8.7% [95% CI, 3.9%
      13.1%]). The independent effect of the nursing quality improvement intervention
      was not significant for all outcomes. Interactions between the 2 interventions
      were only significant for the supine sleep position. Conclusions and Relevance:
      Among mothers of healthy term newborns, a mobile health intervention, but not a
      nursing quality improvement intervention, improved adherence to infant safe sleep
      practices compared with control interventions. Whether widespread implementation
      is feasible or if it reduces sudden and unexpected infant death rates remains to
      be studied. Trial Registration: clinicaltrials.gov Identifier: NCT01713868.

PMID- 28742916
TI  - And Then Came the PACS.

PMID- 28742918
TI  - Deceptive Lyme Disease Diagnosis Linked With Serious Infections.

PMID- 28742919
TI  - Decline in Student Tobacco Use.

PMID- 28742920
TI  - Automated three-dimensional morphology-based clustering of human erythrocytes
      with regular shapes: stomatocytes, discocytes, and echinocytes.
AB  - We present unsupervised clustering methods for automatic grouping of human red
      blood cells (RBCs) extracted from RBC quantitative phase images obtained by
      digital holographic microscopy into three RBC clusters with regular shapes,
      including biconcave, stomatocyte, and sphero-echinocyte. We select some good
      features related to the RBC profile and morphology, such as RBC average
      thickness, sphericity coefficient, and mean corpuscular volume, and clustering
      methods, including density-based spatial clustering applications with noise, k
      medoids, and k-means, are applied to the set of morphological features. The
      clustering results of RBCs using a set of three-dimensional features are compared
      against a set of two-dimensional features. Our experimental results indicate that
      by utilizing the introduced set of features, two groups of biconcave RBCs and old
      RBCs (suffering from the sphero-echinocyte process) can be perfectly clustered.
      In addition, by increasing the number of clusters, the three RBC types can be
      effectively clustered in an automated unsupervised manner with high accuracy. The
      performance evaluation of the clustering techniques reveals that they can assist
      hematologists in further diagnosis.

PMID- 28742921
TI  - Quantitative model of diffuse speckle contrast analysis for flow measurement.
AB  - Diffuse speckle contrast analysis (DSCA) is a noninvasive optical technique
      capable of monitoring deep tissue blood flow. However, a detailed study of the
      speckle contrast model for DSCA has yet to be presented. We deduced the
      theoretical relationship between speckle contrast and exposure time and further
      simplified it to a linear approximation model. The feasibility of this linear
      model was validated by the liquid phantoms which demonstrated that the slope of
      this linear approximation was able to rapidly determine the Brownian diffusion
      coefficient of the turbid media at multiple distances using multiexposure speckle
      imaging. Furthermore, we have theoretically quantified the influence of optical
      property on the measurements of the Brownian diffusion coefficient which was a
      consequence of the fact that the slope of this linear approximation was
      demonstrated to be equal to the inverse of correlation time of the speckle.

PMID- 28742922
TI  - Intracellular imaging of docosanol in living cells by coherent anti-Stokes Raman
      scattering microscopy.
AB  - Docosanol is an over-the-counter topical agent that has proved to be one of the
      most effective therapies for treating herpes simplex labialis. However, the
      mechanism by which docosanol suppresses lesion formation remains poorly
      understood. To elucidate its mechanism of action, we investigated the uptake of
      docosanol in living cells using coherent anti-Stokes Raman scattering microscopy.
      Based on direct visualization of the deuterated docosanol, we observed highly
      concentrated docosanol inside living cells 24 h after drug treatment. In
      addition, different spatial patterns of drug accumulation were observed in
      different cell lines. In keratinocytes, which are the targeted cells of
      docosanol, the drug molecules appeared to be docking at the periphery of the cell
      membrane. In contrast, the drug molecules in fibroblasts appeared to accumulate
      in densely packed punctate regions throughout the cytoplasm. These results
      suggest that this molecular imaging approach is suitable for the longitudinal
      tracking of drug molecules in living cells to identify cell-specific trafficking
      and may also have implications for elucidating the mechanism by which docosanol
      suppresses lesion formation.

PMID- 28742923
TI  - Comorbid Nighttime Agitation, Sleep Disturbance, and Restless Legs Syndrome: What
      Next?

PMID- 28742924
TI  - Geocoding to Manage Missing Data in a Secondary Analysis of Community-Dwelling,
      Low-Income Older Adults.
AB  - Managing missing data in a secondary analysis is daunting, particularly if the
      data of interest were not included in the parent study design. The current study
      describes the use of geocoding to replace missing data from a parent study for a
      secondary analysis of socioeconomic and neighborhood characteristics in community
      dwelling older adults who are dually eligible for Medicare and Medicaid.
      Geocoding was used to link participants' addresses to data from the American
      Community Survey to replace missing income and neighborhood data. After
      geocoding, data completeness was 100% for neighborhood poverty and education
      composition, and 99.9% for income. Using geocoding provides the gerontological
      nurse researcher with a sample that is more reflective of the population. The
      current findings can be used to tailor neighborhood-centered interventions to
      promote health in low-income older adults. [Res Gerontol Nurs. 2017; 10(4):155
      161.].

PMID- 28742925
TI  - A Capabilities Approach to Environmental Impact on Nursing Home Resident Quality
      of Life.
AB  - Nursing homes are the major provider of intermediate and long-term care outside
      of the hospital setting to individuals whose capacity for self-care is limited
      due to physical or cognitive impairments. Yet, despite their need for assistance,
      residents of nursing homes want to control their lives, set their routines, and
      do enjoyable things. The extent to which residents can maintain autonomy and
      dignity is important. The current study suggests an environmental gerontological
      framework, rooted in a capabilities approach, that can be used to consider
      environmental impact on quality of life in nursing homes. Using a cross-sectional
      survey of nursing home residents in Texas, environmental factors that might
      predict residents' quality of life as well as possible interactions of
      environmental factors and residents' characteristics that might predict well
      being were examined. Environmental orientation and perception of social
      activities were important predictors of residents' quality of life, but
      geographic location and facility size were not important predictors. [Res
      Gerontol Nurs. 2017; 10(4):162-170.].

PMID- 28742926
TI  - Intravenous immunoglobulin as adjunct therapy for refractory pyoderma
      gangrenosum: systematic review of cases and case series.
AB  - Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis. Treatment regimens
      for refractory cases are nonstandardized. Intravenous immunoglobulin (IVIG) is an
      emerging treatment with reported success, but the efficacy of IVIG for PG is
      unknown. In this systematic review of cases and case series, we assessed the
      efficacy of IVIG for the treatment of PG, as observed at our institution and
      reported in the literature. A retrospective chart review at two tertiary care
      hospitals between 2000 and 2015, and literature searches in PubMed/MEDLINE,
      EMBASE and Web of Science from all years were conducted. In total, there were 49
      patients, including 43 patients from 26 articles and six institutional cases.
      There was complete or partial response in 43 (88%) patients and complete response
      in 26 (53%) patients. The mean time to initial response to treatment and
      treatment length were 3.5 (SD 3.3) weeks and 5.9 (SD 7.8) months, respectively.
      On average, 2.6 treatments had been trialled before IVIG initiation. IVIG was
      administered with systemic steroids in 43 (88%) cases. Mild adverse events,
      especially nausea and headache, were reported in 12 (24.5%) patients. Our
      systematic review suggests a potential role for IVIG as adjuvant therapy for
      refractory PG. Prospective clinical trials testing the efficacy of IVIG for
      refractory PG are needed to validate these findings.

PMID- 28742927
TI  - A new model for netrin1 in commissural axon guidance.
AB  - Now-classic experiments characterized netrin1 as a major player in commissural
      axon guidance in the spinal cord. The data suggest a chemotactic model in which
      netrin1 expression in the floor plate forms a concentration gradient that
      attracts commissural axons. New research published independently in Neuron and in
      Nature tests this model by deleting netrin1 specifically in the floor plate.
      Surprisingly, these conditional mutant mice have no overt commissure defects. The
      authors report that netrin1 decorates the pial surface of the spinal cord and
      hindbrain, likely deposited by radial processes of progenitor cells in the
      ventricular zone. They find that deletion of the cue exclusively in the
      ventricular zone causes commissural axons to take aberrant trajectories,
      suggesting a short range, haptotactic guidance mechanism as opposed to
      chemotaxis. This minireview aims to summarize the classic and the new findings
      and offer some interpretations of the data.

PMID- 28742928
TI  - Shotgun mitogenomics across body size classes in a local assemblage of tropical
      Diptera: Phylogeny, species diversity and mitochondrial abundance spectrum.
AB  - Mitochondrial genomes can be assembled readily from shotgun-sequenced DNA
      mixtures of mass-trapped arthropods ("mitochondrial metagenomics"), speeding up
      the taxonomic characterization. Bulk sequencing was conducted on some 800
      individuals of Diptera obtained by canopy fogging of a single tree in Borneo
      dominated by small (<1.5 mm) individuals. Specimens were split into five body
      size classes for DNA extraction, to equalize read numbers across specimens and to
      study how body size, a key ecological trait, interacts with species and
      phylogenetic diversity. Genome assembly produced 304 orthologous mitochondrial
      contigs presumed to each represent a different species. The small-bodied fraction
      was the by far most species-rich (187 contigs). Identification of contigs was
      through phylogenetic analysis together with 56 reference mitogenomes, which
      placed most of the Bornean community into seven clades of small-bodied species,
      indicating phylogenetic conservation of body size. Mapping of shotgun reads
      against the mitogenomes showed wide ranges of read abundances within each size
      class. Ranked read abundance plots were largely log-linear, indicating a
      uniformly filled abundance spectrum, especially for small-bodied species. Small
      bodied species differed greatly from other size classes in neutral metacommunity
      parameters, exhibiting greater levels of immigration, besides greater total
      community size. We suggest that the established uses of mitochondrial
      metagenomics for analysis of species and phylogenetic diversity can be extended
      to parameterize recent theories of community ecology and biodiversity, and by
      focusing on the number mitochondria, rather than individuals, a new theoretical
      framework for analysis of mitochondrial abundance spectra can be developed that
      incorporates metabolic activity approximated by the count of mitochondria.

PMID- 28742929
TI  - A Structurally Characterized CuIII Complex Supported by a Bis(anilido) Ligand and
      Its Oxidative Catalytic Activity.
AB  - Three copper(II) complexes of the (R,R)-N,N'-bis(3,5-di-tert-butyl-2
      aminobenzylidene)-1,2-diaminocyclohexane ligand, namely [Cu(N L)], [Cu(N LH)]+
      and [Cu(N LH2 )]2+ , were prepared and structurally characterized. In [Cu(N LH2
      )]2+ the copper ion lies in an octahedral geometry with the aniline groups
      coordinated in equatorial positions. In [Cu(N L)] the anilines are deprotonated
      (anilido moieties) and coordinated to an almost square-planar metal ion. Complex
      [Cu(N L)] displays two oxidation waves at E1/2ox, 1 =-0.14 V and E1/2ox, 2 =0.36
      V vs. Fc+ /Fc in CH2 Cl2 . Complex [Cu(N LH2 )]2+ displays an irreversible
      oxidation wave at high potential (1.21 V), but shows a readily accessible and
      reversible metal-centered reduction at E1/2red =-0.67 V (CuII /CuI redox couple).
      Oxidation of [Cu(N L)] by AgSbF6 produces [Cu(N L)](SbF6 ), which was isolated as
      single crystals. X-ray structure analysis discloses a contraction of the
      coordination sphere by 0.05 A upon oxidation, supporting a metal-centered
      process. Complex [Cu(N L)](SbF6 ) displays an intense NIR band at 1260 nm
      corresponding to an anilido-to-copper(III) charge transfer transition. This
      compound slowly evolves in CH2 Cl2 solution towards [Cu(N LH)](SbF6 ), which is a
      copper(II) complex comprised of both anilido and aniline groups coordinated to
      the metal center. The copper(III) complex [Cu(N L)](SbF6 ) is an efficient
      catalyst for benzyl alcohol oxidation, with 236 TON in 24 h at 298 K, without
      additives other than oxygen and a base.

PMID- 28742930
TI  - Information about first-trimester screening and self-reported distress among
      pregnant women and partners - comparing two methods of information giving in
      Sweden.
AB  - INTRODUCTION: Balanced information before prenatal diagnosis (PND) aims to help
      expectant parents to make an informed choice. However, it is important that the
      information does not increase the expectant parents' psychological distress. The
      aim was to examine psychological distress among expectant parents, before and
      after receiving information about PND, to evaluate the possible differences
      between two different procedures of information giving, and to evaluate the
      association between satisfaction with the information and psychological distress.
      MATERIAL AND METHODS: A longitudinal design, based on questionnaire data from 380
      expectant parents from four counties in Sweden. The measurement points; T1,
      before the information about PND was given and T2, 2 weeks after the prenatal
      screening or 15 weeks of gestation. The Hospital Anxiety and Depression Scale
      (HADS) and the Swedish version of the Cambridge Worrying Scale (CWS) measured
      psychological distress. The Satisfaction with Genetic Counseling Scale (SCS)
      measured satisfaction with information about PND. RESULTS: The rate of
      psychological distress was stable among the pregnant women, but decreased among
      their partners, after the information was received. General anxiety and the
      social-medical dimension of pregnancy-related worry decreased among the
      participants who received information, using the more distinct two-stage process
      (group A), but was unchanged in group B (less distinct two-stage process). Health
      related worry decreased in both groups, whereas relational worry and level of
      depressive symptoms were unchanged in both groups. CONCLUSION: Information about
      PND does not increase the psychological distress among expectant parents. A more
      distinct two-stage process of information giving might even decrease their
      anxiety.

PMID- 28742931
TI  - Dynamics of lipids and metabolites during the cell cycle of Chlamydomonas
      reinhardtii.
AB  - Metabolites and lipids are the final products of enzymatic processes,
      distinguishing the different cellular functions and activities of single cells or
      whole tissues. Understanding these cellular functions within a well-established
      model system requires a systemic collection of molecular and physiological
      information. In the current report, the green alga Chlamydomonas reinhardtii was
      selected to establish a comprehensive workflow for the detailed multi-omics
      analysis of a synchronously growing cell culture system. After implementation and
      benchmarking of the synchronous cell culture, a two-phase extraction method was
      adopted for the analysis of proteins, lipids, metabolites and starch from a
      single sample aliquot of as little as 10-15 million Chlamydomonas cells. In a
      proof of concept study, primary metabolites and lipids were sampled throughout
      the diurnal cell cycle. The results of these time-resolved measurements showed
      that single compounds were not only coordinated with each other in different
      pathways, but that these complex metabolic signatures have the potential to be
      used as biomarkers of various cellular processes. Taken together, the developed
      workflow, including the synchronized growth of the photoautotrophic cell culture,
      in combination with comprehensive extraction methods and detailed metabolic
      phenotyping has the potential for use in in-depth analysis of complex cellular
      processes, providing essential information for the understanding of complex
      biological systems.

PMID- 28742932
TI  - A pilot randomized clinical trial testing integrated 12-Step facilitation (iTSF)
      treatment for adolescent substance use disorder.
AB  - BACKGROUND AND AIMS: The integration of 12-Step philosophy and practices is
      common in adolescent substance use disorder (SUD) treatment programs,
      particularly in North America. However, although numerous experimental studies
      have tested 12-Step facilitation (TSF) treatments among adults, no studies have
      tested TSF-specific treatments for adolescents. We tested the efficacy of a novel
      integrated TSF. DESIGN: Explanatory, parallel-group, randomized clinical trial
      comparing 10 sessions of either motivational enhancement therapy/cognitive
      behavioral therapy (MET/CBT; n = 30) or a novel integrated TSF (iTSF; n = 29),
      with follow-up assessments at 3, 6 and 9 months following treatment entry.
      SETTING: Out-patient addiction clinic in the United States. PARTICIPANTS:
      Adolescents [n = 59; mean age = 16.8 (1.7) years; range = 14-21; 27% female; 78%
      white]. INTERVENTION AND COMPARATOR: The iTSF integrated 12-Step with
      motivational and cognitive-behavioral strategies, and was compared with state-of
      the-art MET/CBT for SUD. MEASUREMENTS: Primary outcome: percentage days abstinent
      (PDA); secondary outcomes: 12-Step attendance, substance-related consequences,
      longest period of abstinence, proportion abstinent/mostly abstinent, psychiatric
      symptoms. FINDINGS: Primary outcome: PDA was not significantly different across
      treatments [b = 0.08, 95% confidence interval (CI) = -0.08 to 0.24, P = 0.33;
      Bayes' factor = 0.28). SECONDARY OUTCOMES: during treatment, iTSF patients had
      substantially greater 12-Step attendance, but this advantage declined thereafter
      (b = -0.87; 95% CI = -1.67 to 0.07, P = 0.03). iTSF did show a significant
      advantage at all follow-up points for substance-related consequences (b = -0.42;
      95% CI = -0.80 to -0.04, P < 0.05; effect size range d = 0.26-0.71). Other
      secondary outcomes did not differ significantly between treatments, but effect
      sizes tended to favor iTSF. Throughout the entire sample, greater 12-Step meeting
      attendance was associated significantly with longer abstinence during (r = 0.39,
      P = 0.008), and early following (r = 0.30, P = 0.049), treatment. CONCLUSION:
      Compared with motivational enhancement therapy/cognitive-behavioral therapy
      (MET/CBT), in terms of abstinence, a novel integrated 12-Step facilitation
      treatment for adolescent substance use disorder (iTSF) showed no greater
      benefits, but showed benefits in terms of 12-Step attendance and consequences.
      Given widespread use of combinations of 12-Step, MET and CBT in adolescent
      community out-patient settings in North America, iTSF may provide an integrated
      evidence-based option that is compatible with existing practices.

PMID- 28742933
TI  - Gene expression is more strongly influenced by age than caste in the ant Lasius
      niger.
AB  - Phenotypic plasticity, where a single genome can give rise to different
      phenotypes, underlies many remarkable features of the natural world and occurs in
      a wide range of organisms. Understanding the transcriptional differences that
      underlie plastic phenotypes remains a major unsolved problem in biology. In many
      ants, females can develop into either queens or workers, two phenotypes with
      different morphology, behaviour and longevity. In comparison with workers, queens
      are larger, more fecund and longer lived. Here, we study gene expression
      differences between queens and workers in the ant Lasius niger. The analysis of
      age- and tissue-specific RNA sequencing showed that patterns of caste-biased gene
      expression vary considerably between ages and tissues. Expression was more
      tightly linked to age than caste despite the important morphological and
      behavioural differences between queens and workers. Our data allowed us to
      identify genes that are consistently biased across biological contexts. Caste
      biased genes showed faster rates of molecular evolution, lower levels of DNA
      methylation and greater variability in expression than unbiased genes. Our
      results indicate that a substantial proportion of caste-biased expression is
      ephemeral and that taking account of age and tissue is critical to understanding
      the transcriptomic basis of plastic phenotypes. By contrast, the biological
      context of expression bias did not broadly affect methylation or the rate of
      evolution. The faster rate of evolution and greater variability of expression of
      caste-biased genes indicate that caste-biased genes evolve from loosely regulated
      genes that can be co-opted for caste-specific tasks because of the lax control
      over their expression.

PMID- 28742934
TI  - Efficient Photoelectrochemical Reduction of Carbon Dioxide to Formic Acid: A
      Functionalized Ionic Liquid as an Absorbent and Electrolyte.
AB  - Photoelectrochemical (PEC) reduction of carbon dioxide (CO2 ) is a potential
      method for production of fuels and chemicals from a C1 feedstock accumulated in
      the atmosphere. However, the low solubility of CO2 in water, and complicated
      processes associated with capture and conversion, render CO2 conversion
      inefficient. A new concept is proposed in which a PEC system is used to capture
      and convert CO2 into formic acid. The process is assisted by an ionic liquid (1
      aminopropyl-3-methylimidazolium bromide) aqueous solution, which functions as an
      absorbent and electrolyte at ambient temperature and pressure. Within this PEC
      reduction strategy, the ionic liquid plays a critical role in promoting the
      conversion of CO2 to formic acid and suppressing the reduction of H2 O to H2 . At
      an applied voltage of 1.7 V, the Faradaic efficiency for formic acid production
      is as high as 94.1 % and the electro-to-chemical efficiency is 86.2 %.

PMID- 28742935
TI  - Response to 'Telling the whole story about simulation-based education'.

PMID- 28742936
TI  - Benefits and limitations of belatacept in 4 hand-transplanted patients.
AB  - Belatacept (cytotoxic T-lymphocyte-associated protein 4 Ig) is an emerging
      treatment in kidney transplantation. Lack of nephrotoxicity and possibly an
      inhibitory effect on the development of donor-specific antibodies (DSAs) make it
      an interesting agent in hand transplantation. To reduce calcineurin inhibitor
      immunosuppression and preserve kidney function, we have added belatacept to the
      therapeutic regimen of 4 hand-transplanted patients at month 4 and at 6, 9, and
      13 years after hand-forearm transplantation. Patients received 5 mg/kg belatacept
      every 2 weeks, and the dosing interval was extended to 4 weeks after 5
      applications. Belatacept was initially well tolerated in all cases. Two patients
      were weaned to a low-dose tacrolimus monotherapy together with monthly belatacept
      applications. One patient is taking belatacept with lowered tacrolimus and
      sirolimus trough levels. A fourth patient had significant levels of DSAs at time
      of conversion and progressed to a severe necrotizing rejection early despite an
      unaltered baseline immunosuppression. Finger skin necrosis and histologic signs
      of severe chronic allograft vasculopathy eventually led to amputation of the
      graft. Implementation of belatacept can be beneficial in hand transplantation.
      However, our findings indicated both potential and caution and reflection of the
      immunologic state at the time of conversion.

PMID- 28742937
TI  - Models for discovery of targeted therapy in genetic epileptic encephalopathies.
AB  - Epileptic encephalopathies are severe disorders emerging in the first days to
      years of life that commonly include refractory seizures, various types of
      movement disorders, and different levels of developmental delay. In recent years,
      many de novo occurring variants have been identified in individuals with these
      devastating disorders. To unravel disease mechanisms, the functional impact of
      detected variants associated with epileptic encephalopathies is investigated in a
      range of cellular and animal models. This review addresses efforts to advance and
      use such models to identify specific molecular and cellular targets for the
      development of novel therapies. We focus on ion channels as the best-studied
      group of epilepsy genes. Given the clinical and genetic heterogeneity of
      epileptic encephalopathy disorders, experimental models that can reflect this
      complexity are critical for the development of disease mechanisms-based targeted
      therapy. The convergence of technological advances in gene sequencing, stem cell
      biology, genome editing, and high throughput functional screening together with
      massive unmet clinical needs provides unprecedented opportunities and imperatives
      for precision medicine in epileptic encephalopathies.

PMID- 28742938
TI  - Sexes in gynodioecious Geranium sylvaticum do not differ in their isotopic
      signature or photosynthetic capacity.
AB  - In gynodioecious plants, females are expected to produce more or better seeds
      than hermaphrodites in order to be maintained within the same population. Even
      though rarely measured, higher seed production can be achieved through
      differences in physiology. In this work, we measured sexual dimorphism in several
      physiological traits in the gynodioecious plant Geranium sylvaticum.
      Photosynthetic rate, stomatal conductance, transpiration rate, WUE and isotopic
      signatures were measured in plants growing in two habitats differing in light
      availability. Females have been reported to produce more seeds than
      hermaphrodites. However, we did not observe any significant difference in seed
      output between the sexes in these experimental populations. Similarly, the sexes
      did not differ in any physiological trait measured. Seed production was strongly
      limited by light availability. Likewise, differences between plants growing in
      full light versus low light were detected in most physiological parameters
      measured. Our results show that the sexes in G. sylvaticum do not show any
      evidence of sexual dimorphism in physiology, which concurred with a lack of
      sexual differences in seed output.

PMID- 28742940
TI  - Functional analysis of the pepper protein phosphatase, CaAIPP1, and its
      interacting partner CaAIRF1: Modulation of ABA signalling and the drought stress
      response.
AB  - Plant adaptive responses to abiotic stress are coordinated by restriction of
      plant growth and development. The plant hormone abscisic acid (ABA) is the key
      regulator of the response to abiotic stress, and its sensitivity determines
      abiotic stress tolerance levels. We previously showed that the E3 ubiquitin
      ligase CaAIRF1 functions as a positive regulator of ABA and drought stress via
      modulation of transcription and stability of the type 2C protein phosphatase
      CaADIP1. Here, we report the identification and functional analysis of a novel
      type 2C phosphatase, CaAIPP1 (Capsicum annuum CaAIRF1 Interacting Protein
      Phosphatase 1). CaAIPP1 interacted with and was ubiquitinated by CaAIRF1. CaAIPP1
      gene expression in pepper leaves was induced by ABA and drought. CaAIPP1
      degradation was faster in crude protein extracts from ABA-treated pepper plants
      than in those from control plants. CaAIPP1-overexpressing plants displayed an ABA
      hyposensitive phenotype during seed germination and seedling growth. Moreover,
      these plants exhibited a drought-sensitive phenotype characterized by high levels
      of transpirational water loss via decreased stomatal closure and reduced leaf
      temperatures. Our data indicate that CaAIPP1 is a negative regulator of the
      drought stress response via ABA-mediated signalling. Our findings provide a
      valuable insight into the plant defence mechanism that operates during drought
      stress.

PMID- 28742939
TI  - Disparate peroxisome-related defects in Arabidopsis pex6 and pex26 mutants link
      peroxisomal retrotranslocation and oil body utilization.
AB  - Catabolism of fatty acids stored in oil bodies is essential for seed germination
      and seedling development in Arabidopsis. This fatty acid breakdown occurs in
      peroxisomes, organelles that sequester oxidative reactions. Import of peroxisomal
      enzymes is facilitated by peroxins including PEX5, a receptor that delivers cargo
      proteins from the cytosol to the peroxisomal matrix. After cargo delivery, a
      complex of the PEX1 and PEX6 ATPases and the PEX26 tail-anchored membrane protein
      removes ubiquitinated PEX5 from the peroxisomal membrane. We identified
      Arabidopsis pex6 and pex26 mutants by screening for inefficient seedling beta
      oxidation phenotypes. The mutants displayed distinct defects in growth, response
      to a peroxisomally metabolized auxin precursor, and peroxisomal protein import.
      The low PEX5 levels in these mutants were increased by treatment with a
      proteasome inhibitor or by combining pex26 with peroxisome-associated
      ubiquitination machinery mutants, suggesting that ubiquitinated PEX5 is degraded
      by the proteasome when the function of PEX6 or PEX26 is reduced. Combining pex26
      with mutations that increase PEX5 levels either worsened or improved pex26
      physiological and molecular defects, depending on the introduced lesion.
      Moreover, elevating PEX5 levels via a 35S:PEX5 transgene exacerbated pex26
      defects and ameliorated the defects of only a subset of pex6 alleles, implying
      that decreased PEX5 is not the sole molecular deficiency in these mutants. We
      found peroxisomes clustered around persisting oil bodies in pex6 and pex26
      seedlings, suggesting a role for peroxisomal retrotranslocation machinery in oil
      body utilization. The disparate phenotypes of these pex alleles may reflect
      unanticipated functions of the peroxisomal ATPase complex.

PMID- 28742941
TI  - Solid-State Transformation of Amorphous Calcium Carbonate to Aragonite Captured
      by CryoTEM.
AB  - Early-stage reaction mechanisms for aragonite-promoting systems are relatively
      unknown compared to the more thermodynamically stable calcium carbonate
      polymorph, calcite. Using cryoTEM and SEM, the early reaction stages taking place
      during aragonite formation were identified in a highly supersaturated solution
      using an alcohol-water solvent, and an overall particle attachment growth
      mechanism was described for the system. In vitro evidence is provided for the
      solid-state transformation of amorphous calcium carbonate to aragonite,
      demonstrating the co-existence of both amorphous and crystalline material within
      the same aragonite needle. This supports non-classical formation of aragonite
      within both a synthetic and biological context.

PMID- 28742942
TI  - Regulation of transposable elements: Interplay between TE-encoded regulatory
      sequences and host-specific trans-acting factors in Drosophila melanogaster.
AB  - Transposable elements (TEs) are mobile genetic elements that can move around the
      genome, and their expression is one precondition for this mobility. Because the
      insertion of TEs in new genomic positions is largely deleterious, the molecular
      mechanisms for transcriptional suppression have been extensively studied. In
      contrast, very little is known about their primary transcriptional regulation.
      Here, we characterize the expression dynamics of TE families in Drosophila
      melanogaster across a broad temperature range (13-29 degrees C). In 71% of the
      expressed TE families, the expression is modulated by temperature. We show that
      this temperature-dependent regulation is specific for TE families and strongly
      affected by the genetic background. We deduce that TEs carry family-specific
      regulatory sequences, which are targeted by host-specific trans-acting factors,
      such as transcription factors. Consistent with the widespread dominant
      inheritance of gene expression, we also find the prevailing dominance of TE
      family expression. We conclude that TE family expression across a range of
      temperatures is regulated by an interaction between TE family-specific regulatory
      elements and trans-acting factors of the host.

PMID- 28742943
TI  - HCV viremic donors with hepatic bridging fibrosis: Are we ready to use their
      livers in the era of direct-acting antivirals?

PMID- 28742944
TI  - Nickel-Catalyzed Enantioselective Conjunctive Cross-Coupling of 9-BBN Borates.
AB  - Catalytic enantioselective conjunctive cross-coupling between 9-BBN borate
      complexes and aryl electrophiles can be accomplished with Ni salts in the
      presence of a chiral diamine ligand. The reactions furnish chiral 9-BBN
      derivatives in an enantioselective fashion and these are converted to chiral
      alcohols and amines, or engaged in other stereospecific C-C bond forming
      reactions.

PMID- 28742945
TI  - Indication of living donor liver transplantation for septuagenarians from double
      equipoise theory.

PMID- 28742946
TI  - The association between obesity and academic performance in youth: a systematic
      review.
AB  - Previous studies have found that obesity could influence academic performance.
      The aim of this study was to systematically review the scientific evidence on the
      association between obesity and academic performance in school children. A
      systematic review of English articles was undertaken by using databases
      PubMed/Medline, ERIC, LILACS, SciELO and Web of Science. Cross-sectional and
      longitudinal studies examining the association between obesity and academic
      performance in children and adolescents, published between January 1990 and
      December 2016, were included. Risk of bias was assessed by using Strengthening
      the Reporting of Observational Studies in Epidemiology. Thirty-four studies (23
      cross-sectional and 11 longitudinal) matched all inclusion criteria and were
      included. Seven studies were classified as low risk of bias, 23 as medium risk
      and four as high risk. After controlling for covariates such as socio-economic
      status, parental education and physical activity, the association between obesity
      and academic performance becomes uncertain for most of the studies (55.9%).
      Therefore, at present, there is insufficient evidence to support a direct link
      between obesity and poor academic performance in school age children. In order to
      clarify this issue, we need more longitudinal studies with adequate sample sizes
      and that control for potential confounders.

PMID- 28742947
TI  - Dendritic Hematite Nanoarray Photoanode Modified with a Conformal Titanium
      Dioxide Interlayer for Effective Charge Collection.
AB  - This paper describes the introduction of a thin titanium dioxide interlayer that
      serves as passivation layer and dopant source for hematite (alpha-Fe2 O3 )
      nanoarray photoanodes. This interlayer is demonstrated to boost the photocurrent
      by suppressing the substrate/hematite interfacial charge recombination, and to
      increase the electrical conductivity by enabling Ti4+ incorporation. The
      dendritic nanostructure of this photoanode with an increased solid-liquid
      junction area further improves the surface charge collection efficiency,
      generating a photocurrent of about 2.5 mA cm-2 at 1.23 V versus the reversible
      hydrogen electrode (vs. RHE) under air mass 1.5G illumination. A photocurrent of
      approximately 3.1 mA cm-2 at 1.23 V vs. RHE could be achieved by addition of an
      iron oxide hydroxide cocatalyst.

PMID- 28742948
TI  - Microbial metabolites and graft versus host disease.
AB  - The health of mammals is a reflection of the diversity and composition of the
      intestinal microbiota. Alterations in the composition and functions of the
      intestinal microbiota have been implicated in multiple disease processes. The
      impact of the microbiota in health and disease is in part a function of the
      nutrient processing and release of metabolites. Recent studies have uncovered a
      major role for microbial metabolites in the function of the host immune system by
      which they influence disease processes such as acute graft versus host disease
      (GVHD), which is the main complication of allogeneic hematopoietic cell
      transplantation (allo-HCT). The mechanisms of acute GVHD regulation by the
      complex microbial community and the metabolites released by them are unclear. In
      this review we summarize major findings of how microbial metabolites interact
      with the immune system and discuss how these interactions could impact acute
      GVHD.

PMID- 28742949
TI  - Strategies to increase the efficacy of using gut microbiota for the modulation of
      obesity.
AB  - Obesity is one of the most serious global public health challenges of the 21st
      century. The adjustment of gut microbiota is often recommended as an efficient
      strategy to treat obesity. This modulation of gut microbiota can be performed by
      many methods, including dietary intervention, antibiotic application, the use of
      prebiotics and probiotics, bariatric surgery and faecal microbiota
      transplantation. In most cases, positive effects have been observed in response
      to treatment, but invalid and even contrary effects have also been observed in
      some cases due to factors that are unrelated to intervention methods, such as
      genetic factors, patient age or gender, environmental microbiota, climate,
      geography and lifestyle. These factors can cause variation of gut microbial
      populations and thus should also be taken into consideration when selecting
      modulation strategies.

PMID- 28742950
TI  - Becoming independent: political participation and youth transitions in the
      Scottish referendum.
AB  - Sociological debates on youth engagement with electoral politics play out against
      a backdrop of supposed 'decline' in civic participation (e.g. Putnam , Norris, ),
      in turn contextualized by theories of individualization in 'late' or 'reflexive'
      modernity (Beck, Giddens). However, the enfranchisement of 16 and 17 year olds in
      the 2014 Scottish Independence Referendum catalysed remarkably high levels of
      voter turnout among this youngest group, and was accompanied by apparently
      ongoing political engagement. We explored this engagement among a strategic
      sample of young 'Yes' voters, in the immediate aftermath of this exceptional
      political event. Analysis of qualitative interview data generated an
      unanticipated finding; that interviewees narrated their political engagement
      biographically, articulated their referendum participation reflexively, and
      located their new political ideas, allegiances and actions in the context of
      their own transitions to 'independent' adulthood. This inspired us to rethink
      young people's political engagement in relation to youth transitions. Doing so
      enables a synthesis of divergent strands in the sociology of youth, and offers
      new insights into the combinations of 'personal' agentic and 'political'
      structural factors involved in young people's politicization.

PMID- 28742951
TI  - PROviding Better ACcess To ORgans: A comprehensive overview of organ-access
      initiatives from the ASTS PROACTOR Task Force.
AB  - The American Society of Transplant Surgeons (ASTS) PROviding better Access To
      Organs (PROACTOR) Task Force was created to inform ongoing ASTS organ access
      efforts. Task force members were charged with comprehensively cataloguing current
      organ access activities and organizing them according to stakeholder type. This
      white paper summarizes the task force findings and makes recommendations for
      future ASTS organ access initiatives.

PMID- 28742952
TI  - Naive Simplicity: The Overlooked Piece of the Complexity-Simplicity Paradigm.
AB  - Concepts of simplicity and complexity in modeling have been explored in papers,
      editorials, and talks. The concept is not well understood because there are at
      least two flavors of simplicity. Modelers envision simplicity (i.e., elegant
      simplicity) as the sought-after goal in modeling, but naive simplicity, which is
      the focus of this paper, is commonly unrecognized and dangerous. The problem is
      that naive or simple ideas are often mistaken for settled science and come with
      the prospect of being more wrong than right. The concept of the so-called
      simplicity cycle, in relation to classical problems of carbon-14 age and salinity
      in closed-basin lakes, is used to illustrate these points. The emerging problems
      of water-mosquitoes-diseases show the value of mapping new problems to the
      simplicity cycle. Researchers can "know what they do not know" and avoid the
      dangers of naive simplicity.

PMID- 28742953
TI  - Invited response to "Hyperfiltration After Donation and Living Kidney Donor
      Risk".

PMID- 28742954
TI  - Carbon dioxide elimination by cardiomyocytes: a tale of high carbonic anhydrase
      activity and membrane permeability.

PMID- 28742955
TI  - Bayesian one-step IPD network meta-analysis of time-to-event data using Royston
      Parmar models.
AB  - Network meta-analysis (NMA) combines direct and indirect evidence from trials to
      calculate and rank treatment estimates. While modelling approaches for continuous
      and binary outcomes are relatively well developed, less work has been done with
      time-to-event outcomes. Such outcomes are usually analysed using Cox proportional
      hazard (PH) models. However, in oncology with longer follow-up time, and time
      dependent effects of targeted treatments, this may no longer be appropriate.
      Network meta-analysis conducted in the Bayesian setting has been increasing in
      popularity. However, fitting the Cox model is computationally intensive, making
      it unsuitable for many datasets. Royston-Parmar models are a flexible alternative
      that can accommodate time-dependent effects. Motivated by individual participant
      data (IPD) from 37 cervical cancer trials (5922 women) comparing surgery,
      radiotherapy, and chemotherapy, this paper develops an IPD Royston-Parmar
      Bayesian NMA model for overall survival. We give WinBUGS code for the model. We
      show how including a treatment-ln(time) interaction can be used to conduct a
      global test for PH, illustrate how to test for consistency of direct and indirect
      evidence, and assess within-design heterogeneity. Our approach provides a
      computationally practical, flexible Bayesian approach to NMA of IPD survival
      data, which readily extends to include additional complexities, such as non-PH,
      increasingly found in oncology trials.

PMID- 28742956
TI  - Fluorescence and Sensing Applications of Graphene Oxide and Graphene Quantum
      Dots: A Review.
AB  - Graphene oxide and graphene quantum dots are attractive fluorophores that are
      inexpensive, nontoxic, photostable, water-soluble, biocompatible, and
      environmentally friendly. They find extensive applications in fluorescent
      biosensors and chemosensors, in which they serve as either fluorophores or
      quenchers. As fluorophores, they display tunable photoluminescence emission and
      the "giant red-edge effect". As quenchers, they exhibit a remarkable quenching
      efficiency through either electron transfer or Forster resonance energy transfer
      (FRET) process. In this review, the origin of fluorescence and the mechanism of
      excitation wavelength-dependent fluorescence of graphene oxide and graphene
      quantum dots are discussed. Sensor design strategies based on graphene oxide and
      graphene quantum dots are presented. The applications of these sensors in health
      care, the environment, agriculture, and food safety are highlighted.

PMID- 28742957
TI  - Gambling Disorder and Concurrent Alcohol Use Disorder Treated With Naltrexone.

PMID- 28742958
TI  - Loss of Meaning in the Era of DSM and Psychopharmacology.

PMID- 28742959
TI  - Long Range Corrections for Inhomogeneous Simulations of Mie n-m Potential.
AB  - The long-range correction scheme for dispersion interactions in inhomogeneous
      simulations is generalized to Mie n-m potential. The influence of the cutoff
      distance and lateral dimensions of the simulation box are studied for 8-6, 12-6,
      and 20-6 Mie fluids at two different temperatures (close and far from the
      critical point). For sufficiently large systems (2400 particles, Rc = 3.5sigma)
      equilibrium properties are simulated over the whole vapor-liquid coexistence
      using the inhomogeneous Monte Carlo simulations, and the results are compared
      with the Gibbs Ensemble technique and with the square gradient theory combined
      with the SAFT Mie equation of state.

PMID- 28742960
TI  - Tuning the Redox Properties of Fullerene Clusters within a Metal-Organic Capsule.
AB  - A porphyrin-edged metal-organic tetrahedron forms host-guest complexes containing
      1-4 equiv of fullerene C60, depending on the solvent employed. The molecules of
      C60 were bound anticooperatively within well-defined pockets; an X-ray crystal
      structure of three fullerenes inside the tetrahedron was obtained.
      Electrochemical measurements revealed that the electron-accepting properties of
      the fullerenes inside the capsules were altered depending on the mode of
      encapsulation. The binding of multiple fullerenes was observed to increase the
      electron affinity of the overall cluster, providing a noncovalent method of
      tuning fullerene electronics.

PMID- 28742961
TI  - Solid-Solid Phase Transitions and tert-Butyl and Methyl Group Rotation in an
      Organic Solid: X-ray Diffractometry, Differential Scanning Calorimetry, and Solid
      State 1H Nuclear Spin Relaxation.
AB  - Using solid-state 1H nuclear magnetic resonance (NMR) spin-lattice relaxation
      experiments, we have investigated the effects of several solid-solid phase
      transitions on tert-butyl and methyl group rotation in solid 1,3,5-tri-tert
      butylbenzene. The goal is to relate the dynamics of the tert-butyl groups and
      their constituent methyl groups to properties of the solid determined using
      single-crystal X-ray diffraction and differential scanning calorimetry (DSC). On
      cooling, the DSC experiments see a first-order, solid-solid phase transition at
      either 268 or 155 K (but not both) depending on thermal history. The 155 K
      transition (on cooling) is identified by single-crystal X-ray diffraction to be
      one from a monoclinic phase (above 155 K), where the tert-butyl groups are
      disordered (that is, with a rotational 6-fold intermolecular potential
      dominating), to a triclinic phase (below 155 K), where the tert-butyl groups are
      ordered (that is, with a rotational 3-fold intermolecular potential dominating).
      This transition shows very different DSC scans when both a 4.7 mg polycrystalline
      sample and a 19 mg powder sample are used. The 1H spin-lattice relaxation
      experiments with a much larger 0.7 g sample are very complicated and, depending
      on thermal history, can show hysteresis effects over many hours and over very
      large temperature ranges. In the high-temperature monoclinic phase, the tert
      butyl groups rotate with NMR activation energies (closely related to rotational
      barriers) in the 17-23 kJ mol-1 range, and the constituent methyl groups rotate
      with NMR activation energies in the 7-12 kJ mol-1 range. In the low-temperature
      triclinic phase, the rotations of the tert-butyl groups and their methyl groups
      in the aromatic plane are quenched (on the NMR time scale). The two out-of-plane
      methyl groups in the tert-butyl groups are rotating with activation energies in
      the 5-11 kJ mol-1 range.

PMID- 28742962
TI  - Characterization of Intramolecular Interactions of Cytochrome c Using Hydrogen
      Deuterium Exchange-Trapped Ion Mobility Spectrometry-Mass Spectrometry and
      Molecular Dynamics.
AB  - Globular proteins, such as cytochrome c (cyt c), display an organized native
      conformation, maintained by a hydrogen bond interaction network. In the present
      work, the structural interrogation of kinetically trapped intermediates of cyt c
      was performed by correlating the ion-neutral collision cross section (CCS) and
      charge state with the starting solution conditions and time after desolvation
      using collision induced activation (CIA), time-resolved hydrogen/deuterium back
      exchange (HDX) and trapped ion mobility spectrometry-mass spectrometry (TIMS-MS).
      The high ion mobility resolving power of the TIMS analyzer allowed the
      identification of new ion mobility bands, yielding a total of 63 mobility bands
      over the +6 to +21 charge states and 20 mobility bands over the -5 to -10 charge
      states. Mobility selected HDX rates showed that for the same charge state,
      conformers with larger CCS present faster HDX rates in both positive and negative
      ion mode, suggesting that the charge sites and neighboring exchange sites on the
      accessible surface area define the exchange rate regardless of the charge state.
      Complementary molecular dynamic simulations permitted the generation of candidate
      structures and a mechanistic model of the folding transitions from native (N) to
      molten globule (MG) to kinetic intermediates (U) pathways. Our results suggest
      that cyt c major structural unfolding is associated with the distancing of the N-
      and C-terminal helices and subsequent solvent exposure of the hydrophobic, heme
      containing cavity.

PMID- 28742963
TI  - The Spin-Flip Variant of the Algebraic-Diagrammatic Construction Yields the
      Correct Topology of S1/S0 Conical Intersections.
AB  - While the conventional variants of the algebraic-diagrammatic construction (ADC)
      scheme for the polarization propagator are generally incapable of correctly
      describing the topology of S1/S0 conical intersections (CIs), its corresponding
      spin-flip (SF) variant of third-order ADC (ADC(3)) is herein demonstrated to
      successfully reproduce the S1/S0 minimum-energy CI (MECI) of twisted formaldinium
      (H2C?NH2+). Analytical nuclear excited-state gradients of ADC have been used in
      combination with the CIOpt program for the optimization of the MECI without the
      need for nonadiabatic-coupling vectors. For comparison, MS-CASPT2 calculations
      were performed via conventional CI optimization employing analytical nonadiabatic
      coupling vectors. It is shown that SF-ADC(3) yields the correct dimensionality of
      the CI and overall compares very favorably to the MS-CASPT2 results.

PMID- 28742964
TI  - Conformational Flexibility and Self-Association of Fibrinogen in Concentrated
      Solutions.
AB  - We studied the hydrodynamic behavior of fibrinogen, a blood plasma protein
      involved in blood clotting, in a broad 0.3-60 mg/mL range of concentration and 5
      42  degrees C temperature using pulsed-field gradient 1H NMR-diffusometry.
      Arrhenius plots revealed the activation energy for fibrinogen diffusion Ed = 21.3
      kJ/mol at 1.4 mg/mL and 28.4 kJ/mol at 38 mg/mL. We found a dramatic slowdown in
      fibrinogen self-diffusion with concentration beginning at 1.7-3.4 mg/mL, which
      deviated from the standard hard-particle behavior, suggesting a remarkable
      intermolecular entanglement. This concentration dependence was observed
      regardless of the absence or presence of the GPRP peptide (inhibitor of fibrin
      polymerization), and also in samples free of fibrin oligomers. By contrast,
      diffusivity of fibrinogen variant I-9 with truncated C-terminal portions of the
      Aalpha chains was much less concentration-dependent, indicating the importance of
      intermolecular linkages formed by the alphaC regions. Theoretical models combined
      with all-atom molecular dynamics simulations revealed partially bent fibrinogen
      solution conformations that interpolate between a flexible chain and a rigid rod
      observed in the crystal. The results obtained illuminate the important role of
      the alphaC regions in modulating the fibrinogen molecular shape through formation
      of weak intermolecular linkages that control the bulk properties of fibrinogen
      solutions.

PMID- 28742965
TI  - Sequential Tandem Addition to a Tungsten-Trifluorotoluene Complex: A Versatile
      Method for the Preparation of Highly Functionalized Trifluoromethylated
      Cyclohexenes.
AB  - The effects of an electron-withdrawing group on the organic chemistry of an eta2
      bound benzene ring are explored using the complex TpW(NO)(PMe3)(eta2-PhCF3). This
      trifluorotoluene complex was found to undergo a highly regio- and stereoselective
      1,2-addition reaction involving protonation of an ortho carbon followed by
      addition of a carbon nucleophile. The resulting 1,3-diene complexes can undergo a
      second protonation and nucleophilic addition with a range of nucleophiles
      including hydrides, amines, cyanide, and protected enolates. Interestingly, the
      addition of the second proton and nucleophile occurs in a 1,4-fashion, again with
      a high degree of regio- and stereocontrol. Oxidation of the metal allows for the
      isolation of highly substituted trifluoromethylcyclohexenes with as many as four
      stereocenters set by the metal. The ability to synthesize enantio-enriched
      organics was also demonstrated for a diene and a trisubstituted cyclohexene.
      Substitution from an enantio-enriched eta2-dimethoxybenzene complex in neat
      trifluorotoluene yielded enantio-enriched trifluorotoluene complex, which was
      elaborated into cyclohexadienes and cyclohexenes with ee's ranging from 92 to
      99%.

PMID- 28742966
TI  - Decisive Role of Hydrophobicity on the Effect of Alkylammonium Chlorides on
      Protein Stability: A Terahertz Spectroscopic Finding.
AB  - Many biologically important processes involve a subtle interplay between Columbic
      and hydrophobic interactions among molecular groups with water. A comprehensive
      understanding of such processes, specially while occurring simultaneously in the
      same molecule is of practical importance. In this contribution, we report the
      ultrafast (subpicosecond to picosecond) collective hydrogen bond dynamics of
      water in the extended hydration layers in a series of alkylammonium chloride
      salts using THz time domain spectroscopic (TTDS) technique (0.3-1.6 THz (10-55 cm
      1)). We found the THz absorption coefficient (alpha) of the salt solutions
      systematically vary with the salt type. We obtain the hydrogen bond relaxation
      dynamics by fitting the frequency dependent dielectric constants in a multiple
      Debye dielectric relaxation model. We found these salts to transform from being a
      water "structure breaker" to "structure maker" with increasing carbon content. We
      also investigate their effect on a model protein "bovine serum albumin" and found
      a systematic trend toward disrupting the protein secondary structure. The
      associated changes in the protein hydration in the presence of these salts have
      also been investigated using TTDS.

PMID- 28742967
TI  - Molybdenum(0) Dihapto-Coordination of Benzene and Trifluorotoluene: The
      Stabilizing and Chemo-Directing Influence of a CF3 Group.
AB  - The preparation of the complexes TpMo(NO)(DMAP)(eta2-PhCF3) (5) and
      TpMo(NO)(DMAP)(eta2-benzene) (3) is described. The CF3 group is found to
      stabilize the metal-arene bond strength in 5 by roughly 3 kcal/mol compared to
      that in 3, allowing the large-scale synthesis and isolation of the
      trifluorotoluene analogue (5, 37 g, 70%). When a benzene solution of 5 is allowed
      to stand, clean conversion to the benzene analogue 3 occurs, and this complex may
      be precipitated from solution upon the addition of pentane and isolated. The
      trifluorotoluene complex is shown to be a synthetic precursor to functionalized
      cyclohexadienes: In solution, it selectively protonates at the ortho position,
      and the resulting eta2-arenium species undergoes reactions with nucleophiles at
      the adjacent meta carbon. Thus, reactions of 5, triflic acid, and either N
      methylpyrrole or 1-methoxy-2-methyl-1-(trimethylsilyloxy)-1-propene result in 5
      substituted-1,3-cyclohexadienes after removal of the metal.

PMID- 28742968
TI  - Enhancing the Elasticity of Ultrathin Single-Wall Carbon Nanotube Films with
      Colloidal Nanocrystals.
AB  - Thin bilayers of contrasting nanomaterials are ubiquitous in solution-processed
      electronic devices and have potential relevance to a number of applications in
      flexible electronics. Motivated by recent mesoscopic simulations demonstrating
      synergistic mechanical interactions between thin films of single-wall carbon
      nanotubes (SWCNTs) and spherical nanocrystal (NC) inclusions, we use a thin-film
      wrinkling approach to query the compressive mechanics of hybrid
      nanotube/nanocrystal coatings adhered to soft polymer substrates. Our results
      show an almost 2-fold enhancement in the Young modulus of a sufficiently thin
      SWCNT film associated with the presence of a thin interpenetrating overlayer of
      semiconductor NCs. Mesoscopic distinct-element method simulations further support
      the experimental findings by showing that the additional noncovalent interfaces
      introduced by nanocrystals enhance the modulus of the SWCNT network and hinder
      network wrinkling.

PMID- 28742969
TI  - Fabrication of a New Lineage of Artificial Luciferases from Natural Luciferase
      Pools.
AB  - The fabrication of artificial luciferases (ALucs) with unique optical properties
      has a fundamental impact on bioassays and molecular imaging. In this study, we
      developed a new lineage of ALucs with unique substrate preferences by extracting
      consensus amino acids from the alignment of 25 copepod luciferase sequences
      available in natural luciferase pools. The primary sequence was first created
      with a sequence logo generator resulting in a total of 11 sibling sequences.
      Phylogenetic analysis shows that the newly fabricated ALucs form an independent
      branch, genetically isolated from the natural luciferases, and from a prior
      series of ALucs produced by our laboratory using a smaller basis set. The new
      lineage of ALucs were strongly luminescent in living mammalian cells with
      specific substrate selectivity to native coelenterazine. A single-residue-level
      comparison of the C-terminal sequences of new ALucs reveals that some amino acids
      in the C-terminal ends are greatly influential on the optical intensities but
      limited in the color variance. The success of this approach guides on how to
      engineer and functionalize marine luciferases for bioluminescence imaging and
      assays.

PMID- 28742970
TI  - Interaction Behaviors of Fibrinopeptide-A and Graphene with Different Functional
      Groups: A Molecular Dynamics Simulation Approach.
AB  - Graphene as a 2-dimentional material has been widely used in the field of
      biomedical applications. In this study, molecular dynamics simulations are
      carried out on the fibrinopeptide-A and graphene surfaces with N and O
      modifications. A new set of parameters for the CHARMM force field are developed
      to describe the behaviors of the surfaces. Our results indicate that the
      existence of most oxygen and nitrogen groups may enhance the interaction between
      the surfaces and the peptide, whereas the substitutional nitrogen on the graphene
      surface does not make a big difference. The improvement of interaction is not
      only because of the functional group on the surface, but also the defective
      morphology. The defective morphology also clears away the surface water layer.
      Our results suggest that the interactions between graphene biomolecules can be
      affected by functionalizing the surface with different types of functional
      groups, which is in accordance with the theory of material design.

PMID- 28742971
TI  - Evidence for Quinone Redox Chemistry Mediating Daytime and Nighttime NO2-to-HONO
      Conversion on Soil Surfaces.
AB  - Humic acid (HA) is thought to promote NO2 conversion to nitrous acid (HONO) on
      soil surfaces during the day. However, it has proven difficult to identify the
      reactive sites in natural HA substrates. The mechanism of NO2 reduction on soil
      surrogates composed of HA and clay minerals was studied by use of a coated-wall
      flow reactor and cavity-enhanced spectroscopy. Conversion of NO2 to HONO in the
      dark was found to be significant and correlated to the abundance of C-O moieties
      in HA determined from the X-ray photoelectron spectra of the C 1s region. Twice
      as much HONO was formed when NO2 reacted with HA that was photoreduced by
      irradiation with UV-visible light compared to the dark reaction; photochemical
      reactivity was correlated to the abundance of C?O moieties rather than C-O
      groups. Bulk electrolysis was used to generate HA in a defined reduction state.
      Electrochemically reduced HA enhanced NO2-to-HONO conversion by a factor of 2
      relative to non-reduced HA. Our findings suggest that hydroquinones and
      benzoquinones, which are interchangeable via redox equilibria, contribute to both
      thermal and photochemical HONO formation. This conclusion is supported by
      experiments that studied NO2 reactivity on mineral surfaces coated with the model
      quinone, juglone. Results provide further evidence that redox-active sites on
      soil surfaces drive ground-level NO2-to-nitrite conversion in the atmospheric
      boundary layer throughout the day, while amphoteric mineral surfaces promote the
      release of nitrite formed as gaseous HONO.

PMID- 28742972
TI  - Stimuli-Responsive Directional Vesicular Assembly with Tunable Surface
      Functionality and Impact on Enzyme Inhibition.
AB  - The article describes the self-assembly of a series of unsymmetrical bola-shaped
      pi-amphiphiles (NDI-1, NDI-1a, NDI-2, NDI-3, and NDI-4) consisting of a
      hydrophobic naphthalene-diimide (NDI) chromophore attached to a nonionic
      hydrophilic wedge and an anionic headgroup in the two opposite arms of the
      central NDI. By design, only a single hydrazide group is linked either on the
      ionic or nonionic arm of the NDI. NDI-1 and NDI-1a are regioisomers differing
      only in the location of the hydrazide group, placed in the nonionic or ionic arm,
      respectively. NDI-2, NDI-3, and NDI-4 are similar to NDI-1 in the placement of
      the hydrazide group but differ in the nature of the ionic headgroups. Except for
      NDI-2, all of them exhibit spontaneous vesicle structures in water (pH 9.0) as
      established by electron microscopy, small-angle neutron scattering, dynamic light
      scattering, and spectroscopy studies. Supramolecularly assembled oligo
      oxyethylene chains of the hydrophobic wedge exhibited a lower critical solution
      temperature (LCST) at ~40  degrees C, similar to that of covalent polymers.
      Consequently, above the LCST, the bola-amphiphile was converted to a single
      headgroup surfactant, resulting in the collapse of the vesicular structure to
      nanoparticles. In all examples, the dominant H-bonding force among the hydrazide
      groups resulted in unidirectional orientation, leading to the formation of a
      nonsymmetric membrane with the H-bonded chain located at the inner wall.
      Therefore, the functional group displayed in these vesicles could be fully
      dictated by the location of the hydrazide group. Thus, for NDI-1, NDI-3, or NDI
      4, the hydrazide group, located at the nonionic arm, directed the nonionic wedge
      to converge at the inner wall of the vesicle by displaying the anionic headgroups
      toward the outer surface. In contrast, NDI-1a formed a nonionic vesicle because
      in this case anionic headgroups were located at the inner wall of the membrane.
      Furthermore, among NDI-1, NDI-3, and NDI-4, the charge density of the anionic
      surface and accordingly the radius of curvature and particle size could be tuned
      precisely as a function of the extent of charge delocalization in the phenoxide
      or carboxylate headgroup. These distinct self-assembly modes resulted in very
      different abilities of these vesicles for electrostatic-interaction-driven
      biomolecular recognition, which was studied by testing their ability to bind with
      cationic protein chymotripsin and inhibit its enzymatic activity. The enzyme
      inhibition ability followed the order NDI-1 > NDI-3 > NDI-4 > NDI-2 ~ NDI-1a,
      which could be rationalized by their distinct functional group display and
      surface charge density factors.

PMID- 28742973
TI  - Role of vitamin A oral supplementation on oxidative stress and inflammatory
      response in the liver of trained rats.
AB  - The use of dietary supplements to enhance the benefit of exercise training is a
      common practice. The liver is the organ where all substances are metabolized, and
      certain supplements have been associated with liver injury. Vitamin A (VA), a
      liposoluble vitamin stored in the liver, is commonly used as an antioxidant
      supplement. Here, we evaluated the effect of chronic VA supplementation on
      oxidative damage and stress parameters in trained rats. Animals were divided into
      the following groups: sedentary (SE), sedentary/VA (SE+VA), exercise training
      (ET), and exercise training/VA (ET+VA). During 8 weeks, animals were subjected to
      swimming (0%, 2%, 4%, 6% body weight) for 5 days/week and a VA daily intake of
      450 retinol equivalents/day. Parameters were evaluated by enzymatic activity
      analysis, ELISA, and Western blotting. VA caused liver lipid peroxidation and
      protein damage in exercised rats and inhibited the increase in HSP70 expression
      acquired with exercise alone. The ET group showed higher levels of antioxidant
      enzyme activity, and VA inhibited this adaptation. Expression of the pro
      inflammatory cytokines, interleukin (IL)-1beta, and tumor necrosis factor-alpha
      was reduced in the ET+VA group, while the anti-inflammatory cytokine, IL-10, was
      increased. Western blotting showed that both exercised groups had lower levels of
      the receptor for advanced glycation end products, suggesting that VA did not
      affect this receptor. Our study demonstrated that, although VA caused oxidative
      damage, a controlled administration might exert anti-inflammatory effects.
      Further studies with higher VA doses and longer ET interventions would elucidate
      more the effects of the supplementation and exercise on liver parameters.

PMID- 28742974
TI  - Chiropractic curriculum mapping and congruence of the evidence for workplace
      interventions in work-related neck pain.
AB  - OBJECTIVE: The purpose of this study was to provide a best-synthesis summary of
      the literature for effective workplace health promotion interventions (WHPI) for
      work-related mechanical neck pain (MNP) and to determine the congruence between
      knowledge of WHPI for work-related MNP and coverage of MNP in the chiropractic
      postgraduate program at Macquarie University. METHODS: A literature review was
      undertaken to determine effective WHPI for work-related MNP. We searched Cochrane
      Library, PubMed, EMBASE, CINAHL, and PEDro (from 1991 to 2016) for systematic
      reviews and meta-analyses. The PRISMA (2009) 27-item checklist was used to
      critically appraise included articles. Lectures, tutorials, and assessment tasks
      within the chiropractic postgraduate program were mapped to the literature review
      findings and analyzed. RESULTS: There was moderate-quality evidence for
      multidimensional WHPI, including aspects of mental and physical functioning,
      activity performance and modifications, and environmental modifications, to
      reduce MNP and disability in workers, particularly in the long term. Education on
      coverage of MNP and effective WHPI for MNP was inadequately covered although
      congruent with synthesis of current literature. Education on body functions and
      structures and personal factors were the most commonly covered components.
      CONCLUSION: Multidimensional WHPI, focusing on physical, mental, and
      environmental modifications, appear to reduce self-reported MNP primarily in
      office workers. There is adequate congruence between the chiropractic
      postgraduate program at Macquarie University and the published literature on some
      WHPI. However, there is inadequate coverage on aspects of MNP and effective WHPI
      for MNP, particularly those focusing on activity and participation and
      environmental factors.

PMID- 28742975
TI  - Tumor imaging instruction and assessment at chiropractic colleges in North
      America: a pilot study with implications for National Board of Chiropractic
      Examiners content.
AB  - OBJECTIVE: This pilot study tested a survey instrument pertaining to the
      instruction and assessment of tumor imaging in chiropractic training programs.
      The secondary purpose was to gather data regarding credentials of lead
      instructors, textbook and resource use, and tumors taught and assessed. METHODS:
      An electronic survey was distributed to lead tumor imaging instructors at all
      chiropractic colleges in the United States and Canada. A focus group of tumor
      imaging instructors was conducted to clarify ambiguous data. RESULTS: Diplomate
      status with the American Chiropractic Board of Radiology was held by 87.5% of the
      instructor respondents. There were similarities in course content and assessment
      across institutions. A total of 26 tumors were considered clinically significant
      by more than 65% of instructors, 9 tumors were identified as not clinically
      significant by more than 65%, and 4 tumors were considered clinically significant
      by 35% to 65% of instructors. There was correlation between those instructors who
      evaluated on various tumors and those who feel it is important to evaluate such
      tumors (rS = 0.94, p < .001). The focus group addressed the 4 equivocal tumors
      and recommended 3 be added to the list of clinically insignificant tumors.
      CONCLUSION: The survey instrument is ready to be used to conduct a study of all
      clinical areas of the chiropractic curriculum. A total of 12 tumors were
      recommended for removal from National Board of Chiropractic Examiners tests. The
      authors recommend that the Academics Committee of the American Chiropractic Board
      of Radiology share information regarding learning libraries to allow for a richer
      learning experience across all campuses.

PMID- 28742977
TI  - Victoria's low availability of public psychiatric beds and the impact on
      patients, carers and staff.

PMID- 28742978
TI  - Consideration for eliminating conjunctival closure in the enucleation procedure.
AB  - To compare post-operative results and complications in patients who undergo
      enucleation with or without suture closure of the conjunctiva. This was a
      retrospective chart review study. Review of 50 cases of enucleation surgery at
      the University of Arkansas for Medical Sciences and Arkansas Children's Hospital
      between July 2011 and December 2014. Criteria for inclusion in the study were all
      cases of enucleation that had extraocular muscles attached to a spherical orbital
      implant with or without conjunctival closure, and at least 2 months of
      postoperative follow up. Post-operative complications were evaluated. A total of
      36 cases fulfilled the criteria for inclusion in the study; 12 cases with direct
      sutured layered direct closure of Tenon's and then conjunctiva and 24 cases with
      Tenon's capsule sutured closure but without direct conjunctival sutured closure.
      No implant complications were identified in either group (p = 1.0). Mean follow
      up for all groups was 16.71 months (range 2 to 43 mo., SD 11.94). Mean follow up
      for the non-closure group was 14.42 months (range 2.25 to 36 mo., SD 10.35). Two
      cases in the conjunctival closure group developed a conjunctival cyst, affecting
      prosthesis fit, approximately 3 months postoperatively: no such cysts were
      identified in the non-conjunctival closure group. Fisher exact test for cyst
      formation between the two groups was not statistically significant (p = 0.1048).
      Direct conjunctival closure following enucleation surgery does not appear to
      increase the risk of extrusion, exposure, or infection. Foregoing direct closure
      decreases surgical time and reduces cost. It is unclear if this decreases
      conjunctival cyst formation.

PMID- 28742979
TI  - Adult attachment and drinking context as predictors of alcohol problems and
      relationship satisfaction in college students.
AB  - BACKGROUND: Evidence suggests that for young adults, intimate partners influence
      each other's drinking patterns. Therefore, exploration of variables related to
      intimate partner relationships (such as attachment style) could broaden the
      current understanding of risk factors for alcohol problems in this demographic.
      OBJECTIVES: The current study examined the role of drinking context in the
      relationships among insecure attachment, alcohol problems, and relationship
      satisfaction. A path model was hypothesized where the relationship between
      insecure attachment and alcohol problems would be explained via two distinct
      drinking contexts (i.e., drinking with one's partner and drinking away from one's
      partner). It was also hypothesized that the relationship between insecure
      attachment and relationship satisfaction would be explained via these same two
      drinking contexts. METHODS: Participants were 194 undergraduate students ages 18
      25 who reported being in a monogamous intimate partner relationship for at least
      90 days and had also consumed alcohol in the past 90 days. The sample was
      comprised of 76% women and 24% men. RESULTS: The hypothesized direct relationship
      from anxious attachment to alcohol problems was significant; there were also
      significant direct paths from both anxious and avoidant attachment to
      relationship satisfaction. The hypotheses regarding indirect relationships were
      not supported. CONCLUSION: The results of this study contribute to the existing
      literature, in that they suggest that drinking in the context of an intimate
      relationship may not directly affect relationship satisfaction in this
      population. However, relationship functioning still appears to be an important
      variable to consider in the prevention and treatment of alcohol-related problems
      affecting college students.

PMID- 28742981
TI  - Increased precipitation accelerates soil organic matter turnover associated with
      microbial community composition in topsoil of alpine grassland on the eastern
      Tibetan Plateau.
AB  - Large quantities of carbon are stored in alpine grassland of the Tibetan Plateau,
      which is extremely sensitive to climate change. However, it remains unclear
      whether soil organic matter (SOM) in different layers responds to climate change
      analogously, and whether microbial communities play vital roles in SOM turnover
      of topsoil. In this study we measured and collected SOM turnover by the 14C
      method in alpine grassland to test climatic effects on SOM turnover in soil
      profiles. Edaphic properties and microbial communities in the northwestern
      Qinghai Lake were investigated to explore microbial influence on SOM turnover.
      SOM turnover in surface soil (0-10 cm) was more sensitive to precipitation than
      that in subsurface layers (10-40 cm). Precipitation also imposed stronger effects
      on the composition of microbial communities in the surface layer than that in
      deeper soil. At the 5-10 cm depth, the SOM turnover rate was positively
      associated with the bacteria/fungi biomass ratio and the relative abundance of
      Acidobacteria, both of which are related to precipitation. Partial correlation
      analysis suggested that increased precipitation could accelerate the SOM turnover
      rate in topsoil by structuring soil microbial communities. Conversely, carbon
      stored in deep soil would be barely affected by climate change. Our results
      provide valuable insights into the dynamics and storage of SOM in alpine
      grasslands under future climate scenarios.

PMID- 28742980
TI  - Disease relevant modifications of the methylome and transcriptome by particulate
      matter (PM2.5) from biomass combustion.
AB  - Exposure to particulate matter (PM) is recognized as a major health hazard, but
      molecular responses are still insufficiently described. We analyzed the
      epigenetic impact of ambient PM2.5 from biomass combustion on the methylome of
      primary human bronchial epithelial BEAS-2B cells using the Illumina
      HumanMethylation450 BeadChip. The transcriptome was determined by the Affymetrix
      HG-U133 Plus 2.0 Array. PM2.5 induced genome wide alterations of the DNA
      methylation pattern, including differentially methylated CpGs in the promoter
      region associated with CpG islands. Gene ontology analysis revealed that
      differentially methylated genes were significantly clustered in pathways
      associated with the extracellular matrix, cellular adhesion, function of GTPases,
      and responses to extracellular stimuli, or were involved in ion binding and
      shuttling. Differential methylations also affected tandem repeats. Additionally,
      45 different miRNA CpG loci showed differential DNA methylation, most of them
      proximal to their promoter. These miRNAs are functionally relevant for lung
      cancer, inflammation, asthma, and other PM-associated diseases. Correlation of
      the methylome and transcriptome demonstrated a clear bias toward transcriptional
      activation by hypomethylation. Genes that exhibited both differential methylation
      and expression were functionally linked to cytokine and immune responses,
      cellular motility, angiogenesis, inflammation, wound healing, cell growth,
      differentiation and development, or responses to exogenous matter. Disease
      ontology of differentially methylated and expressed genes indicated their
      prominent role in lung cancer and their participation in dominant cancer related
      signaling pathways. Thus, in lung epithelial cells, PM2.5 alters the methylome of
      genes and noncoding transcripts or elements that might be relevant for PM- and
      lung-associated diseases.

PMID- 28742982
TI  - Investigation of orthologous pathogen recognition gene-rich regions in
      solanaceous species.
AB  - Pathogen receptor proteins such as receptor-like protein (RLP), receptor-like
      kinase (RLK), and nucleotide-binding leucine-rich repeat (NLR) play a leading
      role in plant immunity activation. The genome architecture of such genes has been
      extensively investigated in several plant species. However, we still know little
      about their elaborate reorganization that arose during the plant speciation
      process. Using recently released pepper and eggplant genome sequences, we were
      able to identify 1097 pathogen recognition genes (PRGs) in the cultivated pepper
      Zunla-1 and 775 in the eggplant line Nakate-Shinkuro. The retrieved genes were
      analysed for their tendency to cluster, using different methods to infer the
      means of grouping. Orthologous relationships among clustering loci were found,
      and interesting reshuffling within given loci was observed for each analysed
      species. The information obtained was integrated into a comparative map to
      highlight the evolutionary dynamics in which the PRG loci were involved.
      Diversification of 14 selected PRG-rich regions was also explored using a DNA
      target-enrichment approach. A large number of gene variants were found as well as
      rearrangements of sequences encoding single protein domain and changes in
      chromosome gene order among species. Gene duplication and transposition activity
      have clearly influenced plant genome R-gene architecture and diversification. Our
      findings contribute to addressing several biological questions concerning the
      parallel evolution that occurred between genomes of the family Solanaceae.
      Moreover, the integration of different methods proved a powerful approach to
      reconstruct the evolutionary history in plant families and to transfer important
      biology findings among plant genomes.

PMID- 28742983
TI  - Should adults with diabetes mellitus be vaccinated against hepatitis B virus? A
      systematic review of diabetes mellitus and the progression of hepatitis B
      disease.
AB  - Despite the burden of diabetes mellitus (DM), little is known about the role of
      this and other metabolic syndromes on the severity of hepatitis B virus (HBV)
      chronicity and liver disease progression. The value of hepatitis B vaccination
      and its impact on liver diseases and HCC has been largely demonstrated, adult
      vaccination coverage is however suboptimal and DM diagnosis represents an
      opportunity for the HCP to discuss hepatitis B and other adult vaccinations. We
      performed a systematic literature search to identify studies (January 2000 to
      January 2017) describing liver disease progression among patients with HBV by DM
      status. Risk factors were assessed including the relationship between HBV and non
      alcoholic steatohepatitis (NASH). Data were extracted systematically and assessed
      descriptively. Twenty articles described liver disease progression and one
      article evaluated NASH among subjects with HBV by DM status. Fourteen articles
      reported that DM as a predictor for the outcome, including delayed seroclearance,
      cirrhosis, hepatocellular carcinoma, transplant/mortality and death, whereas no
      association on liver outcomes was found in 7 studies. In summary, our review
      suggests that DM is associated with the progression of severe liver outcomes in
      adults with HBV, although more studies are needed to understand the benefits of
      HBV vaccination in adults with DM and liver-diseases.

PMID- 28742984
TI  - Single versus combined immunoregulatory approach using PD-1 and CTLA-4 modulators
      in controlling sepsis.
AB  - INTRODUCTION: Sepsis is a disease process characterized by an extreme
      inflammatory response followed by a period of severe immunosuppression. In recent
      years, there has been improved survival in the initial immune response during
      systemic inflammatory response syndrome, and compensatory anti-inflammatory
      response, yet is mostly unchanged with 18-30% mortality during the later stage of
      sepsis despite numerous Phase 3 clinical trials. Areas covered: This review
      article presents a critical evaluation of the most promising newer studies aimed
      at improving the immunosuppressive stage of sepsis. Administration of
      DHEA/AED/AET show promise in improving survival. Blockade of signaling pathways
      for PD-1/PD-L1/CTLA-4, and partial blockade of TREM-1 signaling, and modification
      to sTREM-1 and the JAK/STAT pathway are promising methods of restoring host
      immune response and improving survival. While there has been significant
      progress, currently no findings have been translated into effective clinical
      interventions. Expert commentary: Clinical success by immunomodulation with
      individual immune mediator is encouraging and should progress to evaluating
      combined methods of immunoregulation. Since most of the animal studies do not
      reproduce human sepsis, development of better animal models and moving toward
      human studies for intervention will lead to the most beneficial findings in
      translational science.

PMID- 28742986
TI  - Adsorption of mesitylene via mesoporous adsorbents.
AB  - : Mesitylene (or 1,3,5-trimethylbenzene) is a volatile organic compound emitted
      from various industrial processes, e.g., spray coating. Its emissions have become
      a critical issue because mesitylene is toxic and cannot be removed using
      traditional adsorbents, e.g., zeolite (H-ZSM-5; the diameter of mesitylene
      molecules is greater than the pore size of H-ZSM-5). Hence, an adsorbent with a
      large pore size, MCM-41, is used in this study to investigate its adsorption
      capacity for mesitylene and compare with that of H-ZSM-5. Experimental results
      reveal that MCM-41 without Al2O3 exhibits a good adsorption capacity (184 mg/g)
      for the gas stream containing 100 ppm of mesitylene at a relative humidity of
      10%. The adsorption kinetics is well described by the Freundlich isotherm.
      Furthermore, experimental results reveal that MCM-41 is effective for the
      adsorption of low concentrations (10 ppm) of mesitylene. In addition, adsorption
      desorption tests revealed that the sample MCM-41-AS is stable to sustain the
      adsorption capacity after 10 adsorption-desorption cycles. After 10 adsorption
      desorption cycles, MCM-41-AS retains 92.4% of its initial adsorption capacity
      (170 vs. 184 mg/g). Finally, MCM-41 and H-ZSM-5 in series are effective for the
      simultaneous removal of mesitylene and toluene in the gas stream. IMPLICATIONS:
      This study aims to improve the performance of adsorbent for mesitylene, which is
      typically applied in the spray-coating industry. The zeolite MCM-41-AS is
      selected as a candidate for the investigation. Experimental results reveal that
      MCM-41-AS exhibits a good adsorption capacity for mesitylene and that it can be
      integrated with H-ZSM-5-25 for the simultaneous adsorption of mesitylene and
      toluene.

PMID- 28742985
TI  - GABAB receptors suppress burst-firing in reticular thalamic neurons.
AB  - Burst-firing in thalamic neurons is known to play a key role in mediating
      thalamocortical (TC) oscillations that are associated with non-REM sleep and some
      types of epileptic seizure. Within the TC system the primary output of GABAergic
      neurons in the reticular thalamic nucleus (RTN) is thought to induce the de
      inactivation of T-type calcium channels in thalamic relay (TR) neurons, promoting
      burst-firing drive to the cortex and the propagation of TC network activity.
      However, RTN neurons also project back onto other neurons within the RTN. The
      role of this putative negative feedback upon the RTN itself is less well
      understood, although is hypothesized to induce de-synchronization of RTN neuron
      firing leading to the suppression of TC oscillations. Here we tested two
      hypotheses concerning possible mechanisms underlying TC oscillation modulation.
      Firstly, we assessed the burst-firing behavior of RTN neurons in response to
      GABAB receptor activation using acute brain slices. The selective GABAB receptor
      agonist baclofen was found to induce suppression of burst-firing concurrent with
      effects on membrane input resistance. Secondly, RTN neurons express CaV3.2 and
      CaV3.3 T-type calcium channel isoforms known to contribute toward TC burst-firing
      and we examined the modulation of these channels by GABAB receptor activation.
      Utilizing exogenously expressed T-type channels we assessed whether GABAB
      receptor activation could directly alter T-type calcium channel properties.
      Overall, GABAB receptor activation had only modest effects on CaV3.2 and CaV3.3
      isoforms. The only effect that could be predicted to suppress burst-firing was a
      hyperpolarized shift in the voltage-dependence of inactivation, potentially
      causing lower channel availability at membrane potentials critical for burst
      firing. Conversely, other effects observed such as a hyperpolarized shift in the
      voltage-dependence of activation of both CaV3.2 and CaV3.3 as well as increased
      time constant of activation of the CaV3.3 isoform would be expected to enhance
      burst-firing. Together, we hypothesize that GABAB receptor activation mediates
      multiple downstream effectors that combined act to suppress burst-firing within
      the RTN. It appears unlikely that direct GABAB receptor-mediated modulation of T
      type calcium channels is the major mechanistic contributor to this suppression.

PMID- 28742987
TI  - Caring for Children While Working in Agriculture-The Perspectiveof Farmworker
      Parents.
AB  - Access to safe, off-farm childcare is often a challenge for farmworkers with
      young children and is likely to become an increasingly salient barrier as more
      agricultural workers migrate together with families and as the number of women
      entering the agricultural workforce increases. Agriculture is one of the most
      hazardous industries, and the presence of young children in the workplace puts
      them at risk. To better understand the current nature of childcare for farmworker
      families and the challenges to accessing services, this project facilitated in
      person surveys with 132 parents in three communities in Florida. A convenience
      sample that intentionally targeted parents living and working in areas with
      limited access to Migrant and Seasonal Head Start facilities was used to recruit
      participants. Most participants reported childcare access as a challenge. They
      expressed a desire to work in an area based on childcare availability. These
      findings offer agribusiness leaders important data to consider. They also suggest
      that industry support of childcare may be an important workforce investment.
      Findings indicate that high quality, affordable off-farm childcare services could
      serve as a means for attracting farmworkers to regions currently experiencing
      labor shortages. Additional research is warranted to explore this subject in
      diverse geographic areas.

PMID- 28742988
TI  - Publishing Posthumously the Works of a Scholar? A Reflection on Catherine D.
      Ennis's Lecture Paper.

PMID- 28742989
TI  - Agricultural Leaders' Influence on the Safety Culture of Workers.
AB  - Most US farmers are small, independent owner-operators, many of whom are exempt
      from safety regulation and enforcement, as well as age restrictions relative to
      family members performing hazardous tasks. These smaller farms account for a
      disproportionate share of the total fatality and injury statistics from farming
      incidents, contributing to an agriculture-industry death rate that is seven times
      greater than all occupations combined. In contrast, large agricultural
      enterprises that employ larger numbers of non-family workers are more regulated
      and more highly incentivized by economic, supply chain, and societal factors to
      implement cultures of safety, and are more readily influenced by agricultural
      opinion leaders, agribusinesses, farm organizations, and agricultural media.
      These agricultural influencer institutions must find ways to play more
      significant roles in changing the culture on operations that use only family
      labor. They will find willing partners in safety organizations such as the
      Agricultural Safety and Health Council of America (ASHCA), Agricultural
      Extension, and other health and safety advocates, including the National
      Institute for Occupational Safety and Health (NIOSH)-funded agricultural research
      centers. The overall workplace injury statistics for agriculture remain alarming;
      however, with leadership from the larger farm operations, and help from ASHCA,
      academia, the healthcare community, and others, the current culture of workplace
      safety and health in agriculture can be impacted in positive ways.

PMID- 28742990
TI  - Employment status, gender and health in Spanish women.
AB  - The present study analyzed relationships between employment status, gender role
      conformity, and health among adult Spanish women from a biopsychosocial approach.
      We first examined the potential relationship between employment status and
      conformity to feminine norms (CFNI), second, the relationship between employment
      status and general and psychological health, and finally, the relationship
      between CFNI and general and psychological health. Unemployed women (n = 103),
      employed women (n = 144), and full-time homemakers (n = 100) aged 18-70 yr
      completed a survey, including measures of psychological health (GHQ-12), general
      health (self-rated health), and CFNI. Data collection was conducted during 2014.
      Multiple logistic regression analyses produced odds ratios (OR) and 95 petrcent
      confidence intervals (CI) that showed that full-time homemakers were more likely
      to show higher levels of feminine norms conformity (OR = 2.04; 95 percent CI =
      1.13-3.69; p = .017), although these differences were no longer significant when
      controlled for educational level. Unemployed women (OR = 3.27; 95 percent CI =
      1.87-5.73; p < .001) and women who presented greater CFNI (OR = 1.56; 95 percent
      CI = 1.01-2.40; p = .044) were more likely to show psychological morbidity.
      Public health institutions should pay attention to the relevance of employment
      status and gender roles, given the relation of these factors to women's health.

PMID- 28742991
TI  - Sexual inactivity and occurrence of STIs in relation to weight status in women:
      Two large population-based studies.
AB  - The aim of this study was to examine sexual inactivity and occurrence of selected
      sexually transmitted infections in relation to body mass index. We used data from
      two large Danish population-based cross-sectional studies conducted in 1991-1995
      (HPV study: 6869 women, aged 22-32 years) and in 2004-2005 (Liva study: 19,484
      women, aged 18-45 years). Data were collected using a structured interview and
      measured weight, height, high-risk human papillomavirus DNA, Chlamydia DNA for
      the HPV study and a structured questionnaire for the Liva study. Overweight and
      obese women were more likely to have had no lifetime sexual partner or no sexual
      partner in the last year, e.g., obese women had a threefold (95 percent CI: 1.95
      5.04) odds ratio of having had no sexual partner in the last year compared to
      normal weight women. Additionally, overweight and obese women had a lower
      likelihood of genital warts and high-risk human papillomavirus infection. A
      similar tendency was found for self-reported Chlamydia, but not with presence of
      Chlamydia DNA. If higher likelihood of no lifetime or recent sexual partners
      among overweight and obese women reflects unmet sexual needs, it could give rise
      to concern because quality of sexual life is associated with general quality of
      life.

PMID- 28742992
TI  - Utilizing Secondary Agricultural Education Programs to Deliver Evidence-Based
      Grain Safety Training for Young and Beginning Workers.
AB  - Purdue University's Agricultural Safety and Health Program (PUASHP) has
      collaborated with secondary agricultural education programs, including FFA
      Chapters, for over 70 years to deliver and promote agricultural safety and health
      programming. With support from a U.S. Department of Labor Susan Harwood Program
      grant, PUASHP utilized a Developing a Curriculum (DACUM) process to develop,
      implement, and evaluate an evidence-based curriculum for use with young and
      beginning workers, ages 16-20, exposed to hazards associated with grain storage
      and handling. The primary audience was students enrolled in secondary
      agricultural education programs. A review of the literature identified a gap in
      educational resources that specifically addresses this target population. The
      curriculum developed was based on fatality and injury incident data mined from
      Purdue's Agricultural Confined Space Incident Database and input from a panel of
      experts. The process identified 27 learning outcomes and finalized a pool of test
      questions, supported by empirical evidence and confirmed by a panel of experts.
      An alignment process was then completed with the current national standards for
      secondary agricultural education programs. Seventy-two youth, ages 16-20,
      enrolled in secondary-school agricultural education programs, and a smaller group
      of post-secondary students under the age of 21 interested in working in the grain
      industry pilot tested the curriculum. Based on student and instructor feedback,
      the curriculum was refined and submitted to OSHA for approval as part of OSHA's
      online training resources. The curriculum was delivered to 3,665 students, ages
      16-20. A total of 346 pre- and post-tests were analyzed, and the results used to
      confirm content validity and assess knowledge gain. Findings led to additional
      modifications to curriculum content, affirmed knowledge gain, and confirmed
      appropriateness for use with secondary agricultural education programs. The
      curriculum has been promoted nationally and made available for free download from
      www.agconfinedspaces.org . Findings further confirmed the value of delivering
      safety programming through established programs such as secondary agricultural
      education programs and FFA Chapters serving youth.

PMID- 28742993
TI  - Performance and Return to Sport After Achilles Tendon Repair in National Football
      League Players.
AB  - BACKGROUND: Achilles tendon injuries are common in sports, including football.
      The purpose of this study was to determine (1) return-to-sport rate in National
      Football League (NFL) players following Achilles tendon repair, (2) postoperative
      career length and games per season, (3) pre- and postoperative performance, and
      (4) postoperative performance compared with control players matched by position,
      age, years of experience, and performance. METHODS: Publicly available records
      were used to identify NFL players who underwent Achilles tendon repair and
      matched controls were identified. Ninety-five players (98 surgeries) were
      analyzed (mean age 28.2 +/- 2.8 years; mean 5.5 +/- 2 .8 years in NFL at time of
      surgery). Demographic and performance data were collected. Comparisons between
      case and control groups and preoperative and postoperative time points were made
      using paired-samples Student t tests. RESULTS: Seventy-one (72.4%) players were
      able to return to sport in the NFL at a mean of 339.8 +/- 84.8 days following
      surgery. Thirty-one (32%) Achilles tendon repairs were performed during training
      camp or preseason. Controls (3.6 +/- 2.1 years) had a significantly longer NFL
      career ( P < .05) than players who underwent Achilles tendon repair (2.7 +/- 2.1
      years). There was no significant difference in games per season in subsequent
      seasons following surgery compared with controls. Postoperative performance
      scores were significantly worse ( P < .05) for running backs (RBs) (n = 4) and
      linebackers (LBs) (n = 12) compared to preoperative scores. LBs had significantly
      worse postoperative performance scores when compared to matched controls ( P <
      .05). CONCLUSION: Following Achilles tendon repair, less than 75% of players
      returned to the NFL. Postoperative career length was 1 season shorter than
      matched controls. No difference was observed in the number of games per season
      played compared to matched controls. Postoperative performance scores were
      significantly worse for RBs and LBs compared to preoperative and LBs had
      significantly worse postoperative performance when compared to matched controls.
      LEVEL OF EVIDENCE: Level III, retrospective comparative series.

PMID- 28742994
TI  - Unusual Case of a Massive Macroglossia Secondary to Myxedema: A Case Report and
      Literature Review.
AB  - Macroglossia is classified as true macroglossia, which exhibits abnormal
      histology with clinical findings, and relative macroglossia, in which normal
      histology does not correlate with pathologic enlargement. This report describes
      an atypical case of morbidity with massive macroglossia secondary to myxedema;
      the macroglossia enlarged over a 3-month period before being presented to the
      Department of Oral and Maxillofacial Surgery, University of Texas Health Science
      Center at Houston (Houston, TX). Substantial enlargement of the tongue (16 cm
      long * 10 cm wide) was first attributed to angioedema, which was refractory to
      the discontinuation of lisinopril and a C1 esterase inhibitor. A core tongue
      biopsy examination was performed to rule out angioedema, amyloidosis, myxedema,
      and idiopathic muscular hypertrophy. Interstitial tissue was positive for Alcian
      blue and weakly positive for colloidal iron, which are correlated with
      hypothyroidism and a diagnosis of myxedema. However, the macroglossia did not
      resolve after correcting for hypothyroidism. The patient required a wedge
      glossectomy for definitive treatment. She recovered unremarkably, with excellent
      cosmesis and preservation of lingual and hypoglossal function. There are some
      case reports of massive macroglossia but none with myxedema as the primary
      etiology.

PMID- 28742995
TI  - Icaritin induces MC3T3-E1 subclone14 cell differentiation through estrogen
      receptor-mediated ERK1/2 and p38 signaling activation.
AB  - Icaritin (ICT), a hydrolytic product of icariin from the genus Epimedium, has
      many indicated pharmacological and biological activities. Several studies have
      shown that ICT has potential osteoprotective effects, including stimulation of
      osteoblast differentiation and inhibition of osteoclast differentiation. However,
      the molecular mechanism for this anabolic action of ICT remains largely unknown.
      Here, we found that ICT could enhance MC3T3-E1 subclone 14 preosteoblastic cell
      differentiation associated with increased mRNA levels and protein expression of
      the differentiation markers alkaline phosphatase (ALP), type 1 collagen (COL1),
      osteocalcin (OC), osteoponin (OPN) and runt-related transcription factor 2
      (RUNX2), and improved mineralization, confirmed by bone nodule formation and
      collagen synthesis. To characterize the underlying mechanisms, we examined the
      effect of ICT on estrogen receptor (ER) and mitogen-activated protein kinase
      (MAPK) signaling. ICT treatment induced p38 kinase and extracellular signal
      regulated kinase 1/2 (ERK1/2) activation, but it demonstrated at the same time
      point no effect on activation of c-Jun N-terminal kinase (JNK). ER antagonist
      ICI182780, p38 antagonist SB203580 and ERK1/2 antagonist PD98059 markedly
      inhibited the ICT-induced the mRNA expression of ALP, COL1, OC and OPN. ICI182780
      attenuated the ICT-induced phosphorylation of p38 and ERK1/2. These observations
      indicate a potential mechanism of osteogenic effects of ICT involving the ERK1/2
      and p38 pathway activation through the ER.

PMID- 28742996
TI  - How Primordial Germ Cells Destroy Somatic Signals.
AB  - The Germ Cell-Less (GCL) protein is a key regulator of primordial germ cell (PGC)
      formation in Drosophila embryos. Reporting in this issue of Developmental Cell,
      Pae et al. (2017) show that GCL blocks somatic cell fate by specifically
      destroying the Torso Receptor Tyrosine Kinase.

PMID- 28742997
TI  - ABL to Integrate Opposing Cellular Growth Signals.
AB  - Growth factor signaling has long been known to stimulate cellular growth and
      motility. That it might also directly promote repulsive signaling, however, is a
      surprising finding reported by Yoon et al. (2017) in this issue of Developmental
      Cell.

PMID- 28742998
TI  - Reading the Centromere Epigenetic Mark.
AB  - Centromeres epitomize the central problem of propagating non-DNA sequence-based
      information across generations. In this issue of Developmental Cell, Hori et al.
      (2017) and French et al. (2017) show that the centromere-associated protein KNL
      2/M18BP1 reads the centromere epigenetic code to maintain centromere identity.

PMID- 28742999
TI  - Adding Polyamine Metabolism to the mTORC1 Toolkit in Cell Growth and Cancer.
AB  - The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is a major
      nutrient sensor and regulator of cellular metabolic flux. Reporting recently in
      Nature, Zabala-Letona et al. (2017) show that mTORC1 regulates an additional
      branch of metabolism in the cell-polyamine synthesis-that is important for
      prostate cancer tumorigenicity.

PMID- 28743000
TI  - Cilia Control Fat Deposition during Tissue Repair.
AB  - Fibro/adipogenic progenitors (FAPs) are emerging as crucial regulators of fibrous
      and fat deposits during skeletal muscle regeneration. In a recent issue of Cell,
      Kopinke et al. (2017) report that primary cilia induce the adipogenic fate of
      FAPs in injured and diseased muscle by restraining Hedgehog signaling.

PMID- 28743001
TI  - GCL and CUL3 Control the Switch between Cell Lineages by Mediating Localized
      Degradation of an RTK.
AB  - The separation of germline from somatic lineages is fundamental to reproduction
      and species preservation. Here, we show that Drosophila Germ cell-less (GCL) is a
      critical component in this process by acting as a switch that turns off a somatic
      lineage pathway. GCL, a conserved BTB (Broad-complex, Tramtrack, and Bric-a-brac)
      protein, is a substrate-specific adaptor for Cullin3-RING ubiquitin ligase
      complex (CRL3GCL). We show that CRL3GCL promotes PGC fate by mediating
      degradation of Torso, a receptor tyrosine kinase (RTK) and major determinant of
      somatic cell fate. This mode of RTK degradation does not depend upon receptor
      activation but is prompted by release of GCL from the nuclear envelope during
      mitosis. The cell-cycle-dependent change in GCL localization provides
      spatiotemporal specificity for RTK degradation and sequesters CRL3GCL to prevent
      it from participating in excessive activities. This precisely orchestrated
      mechanism of CRL3GCL function and regulation defines cell fate at the single-cell
      level.

PMID- 28743002
TI  - Drosophila Histone Demethylase KDM4A Has Enzymatic and Non-enzymatic Roles in
      Controlling Heterochromatin Integrity.
AB  - Eukaryotic genomes are broadly divided between gene-rich euchromatin and the
      highly repetitive heterochromatin domain, which is enriched for proteins critical
      for genome stability and transcriptional silencing. This study shows that
      Drosophila KDM4A (dKDM4A), previously characterized as a euchromatic histone H3
      K36 demethylase and transcriptional regulator, predominantly localizes to
      heterochromatin and regulates heterochromatin position-effect variegation (PEV),
      organization of repetitive DNAs, and DNA repair. We demonstrate that dKDM4A
      demethylase activity is dispensable for PEV. In contrast, dKDM4A enzymatic
      activity is required to relocate heterochromatic double-strand breaks outside the
      domain, as well as for organismal survival when DNA repair is compromised.
      Finally, DNA damage triggers dKDM4A-dependent changes in the levels of H3K56me3,
      suggesting that dKDM4A demethylates this heterochromatic mark to facilitate
      repair. We conclude that dKDM4A, in addition to its previously characterized role
      in euchromatin, utilizes both enzymatic and structural mechanisms to regulate
      heterochromatin organization and functions.

PMID- 28743003
TI  - Patterned Disordered Cell Motion Ensures Vertebral Column Symmetry.
AB  - The biomechanics of posterior embryonic growth must be dynamically regulated to
      ensure bilateral symmetry of the spinal column. Throughout vertebrate trunk
      elongation, motile mesodermal progenitors undergo an order-to-disorder transition
      via an epithelial-to-mesenchymal transition and sort symmetrically into the left
      and right paraxial mesoderm. We combine theoretical modeling of cell migration in
      a tail-bud-like geometry with experimental data analysis to assess the importance
      of ordered and disordered cell motion. We find that increasing order in cell
      motion causes a phase transition from symmetric to asymmetric body elongation. In
      silico and in vivo, overly ordered cell motion converts normal anisotropic fluxes
      into stable vortices near the posterior tail bud, contributing to asymmetric cell
      sorting. Thus, disorder is a physical mechanism that ensures the bilateral
      symmetry of the spinal column. These physical properties of the tissue connect
      across scales such that patterned disorder at the cellular level leads to the
      emergence of organism-level order.

PMID- 28743004
TI  - Association of M18BP1/KNL2 with CENP-A Nucleosome Is Essential for Centromere
      Formation in Non-mammalian Vertebrates.
AB  - Centromeres are specified and maintained by sequence-independent epigenetic
      mechanisms through the incorporation of CENP-A into centromeres. Given that CENP
      A incorporation requires the Mis18 complex to be in the centromere region, it is
      necessary to precisely understand how the Mis18 complex localizes to the
      centromere region. Here, we showed that centromere localization of the Mis18
      complex depends on CENP-A, but not CENP-C or CENP-T, in chicken DT40 cells.
      Furthermore, we demonstrated that M18BP1/KNL2, a member of the Mis18 complex,
      contained the CENP-C-like motif in chicken and other vertebrates, which is
      essential for centromere localization and M18BP1/KNL2 function in DT40 cells. We
      also showed that in vitro reconstituted CENP-A nucleosome, but not H3 nucleosome,
      bound to the CENP-C-like motif containing M18BP1/KNL2. Based on these results, we
      conclude that M18BP1/KNL2 is essential for centromere formation through direct
      binding to CENP-A nucleosome in non-mammalian vertebrates. This explains how new
      CENP-A recognizes the centromere position.

PMID- 28743006
TI  - Restoring low-input high-diversity grasslands as a potential global resource for
      biofuels.
AB  - Reducing meat consumption by humans and shifting to more efficient plant and
      animal protein sources could potentially free up large areas of pasture and
      feedcrop agricultural land for restoration or conversion to low-input high
      diversity (LIHD) grasslands. LIHD grasslands improve biodiversity, carbon
      sequestration, erosion control, water storage, while also providing opportunities
      to produce biofuels. We examined the potential of converting pastures globally,
      and animal feedstock agricultural lands in the USA and Brazil, to LIHD biomass
      sources and the capacity of these systems to meet national energy demands via (1)
      cellulosic ethanol and (2) integrated gasification and combined cycle technology
      with Fischer-Tropsch hydrocarbon synthesis (IGCC-FT) processing. Our analyses,
      which we argue are conservative, indicate that large amounts of energy, far in
      excess of many country's current demands, can potentially be produced from IGCC
      FT processing of grassland biomass grown on converted pastures, especially in
      tropical developing countries. Over 40 countries could meet >=100% of their
      domestic demands for electricity, gasoline, and diesel. If energy products were
      shared between countries, the 95 countries with positive energy production yields
      could meet 46%, 28%, and 39% of their combined electricity, gasoline, and diesel
      demands, respectively. While it is clearly unrealistic to propose a 100%
      conversion of pasture lands to biofuel production, these analyses highlight the
      potential gains in ecosystem services and energy production that could
      theoretically be achieved on already-managed lands.

PMID- 28743005
TI  - Xenopus laevis M18BP1 Directly Binds Existing CENP-A Nucleosomes to Promote
      Centromeric Chromatin Assembly.
AB  - Vertebrate centromeres are epigenetically defined by nucleosomes containing the
      histone H3 variant, CENP-A. CENP-A nucleosome assembly requires the three-protein
      Mis18 complex (Mis18alpha, Mis18beta, and M18BP1) that recruits the CENP-A
      chaperone HJURP to centromeres, but how the Mis18 complex recognizes centromeric
      chromatin is unknown. Using Xenopus egg extract, we show that direct, cell-cycle
      regulated binding of M18BP1 to CENP-A nucleosomes recruits the Mis18 complex to
      interphase centromeres to promote new CENP-A nucleosome assembly. We demonstrate
      that Xenopus M18BP1 binds CENP-A nucleosomes using a motif that is widely
      conserved except in mammals. The M18BP1 motif resembles a CENP-A nucleosome
      binding motif in CENP-C, and we show that CENP-C competes with M18BP1 for CENP-A
      nucleosome binding at centromeres. We show that both CENP-C and M18BP1 recruit
      HJURP to centromeres for new CENP-A assembly. This study defines cellular
      mechanisms for recruiting CENP-A assembly factors to existing CENP-A nucleosomes
      for the epigenetic inheritance of centromeres.

PMID- 28743007
TI  - Environmental footprints of brick kiln bottom ashes: Geostatistical approach for
      assessment of metal toxicity.
AB  - Coal fired brick kiln factories generate significant of brick kiln bottom ash
      (BKBA) that contaminate soil and water environments of areas near the dumping
      sites through leaching of toxic metals (Pb, Cr, Cd, Zn, Mn, and Cu). However,
      characteristics and environmental effects of BKBAs are yet unknown. We collected
      BKBA samples from 32 strategic locations of two rapidly developing States (West
      Bengal and Assam) of India. Scanning electron microscope images indicated
      spherical and granular structures of BKBAs produced in West Bengal (WBKBA) and
      Assam (ABKBA) respectively; while energy dispersive spectroscopy and analytical
      assessments confirmed substantial occurrence of total organic C and nutrient
      elements (N, P, K, Ca, Mg, and S) in both the BKBAs. FTIR analysis revealed
      greater predominance of organic matter in ABKBAs than WBKBAs. Occurrence of toxic
      metals (Cd, Cr, Pb, Zn, Mn, and Cu) was higher in ABKBAs than in WBKBAs; while
      organic and residual fractions of metals were highly predominant in most of the
      BKBAs. Principal component analysis showed that metal contents and pH were the
      major distinguishing characteristics of the BKBAs generated in the two different
      environmental locations. Human health risk associated with BKBAs generated in
      Assam is of significant concern. Finally, geo-statistical tools enabled to
      predict the spatial distribution patterns of toxic metals contributed by the
      BKBAs in Assam and West Bengal respectively. Assessment of contamination index,
      geo-accumulation index, and ecological risk index revealed some BKBAs to be more
      toxic than others.

PMID- 28743009
TI  - Retromer.
AB  - Lucas and Hierro introduce the retromer and its role in endosomal protein sorting
      and trafficking.

PMID- 28743008
TI  - Wastewater contamination in Antarctic melt-water streams evidenced by virological
      and organic molecular markers.
AB  - Human activities in the Antarctica including tourism and scientific research have
      been raised substantially in the last century with the concomitant impact on the
      Antarctic ecosystems through the release of wastewater mainly from different
      scientific stations activities. The aim of this study was to assess the
      wastewater contamination of surface waters and sediments of three melt-water
      streams (11 sites) by leaking septic tanks located in the vicinity of the
      Uruguayan Scientific Station in the Fildes Peninsula, King George Island,
      Antarctica, during summer 2015. For this purpose, we combined the analysis of
      fecal steroids in sediments by using gas chromatography and six enteric viruses
      in surface waters by quantitative and qualitative PCR. Coprostanol concentrations
      (from 0.03 to 3.31MUgg-1) and fecal steroids diagnostic ratios indicated that
      stations C7 and C8 located in the kitchen stream presented sewage contamination.
      Rotavirus was the only enteric virus detected in five sites with concentration
      ranging from 1.2*105gcL-1 to 5.1*105gcL-1 being three of them located downstream
      from the leaking AINA and Kitchen septic tanks. This study shows for the first
      time the presence of both virological and molecular biomarkers of wastewater
      pollution in surface waters and sediments of three melt-water streams in the
      vicinity of a scientific station in the Antarctica. These results highlight the
      importance of the complementation of these biomarkers in two different matrices
      (surface waters and sediments) to assess wastewater pollution in an Antarctic
      environment related to anthropogenic activities in the area.

PMID- 28743010
TI  - Gloger's rule.
AB  - Delhey introduces the relationship between climatic parameters like humidity or
      temperature and animal coloration.

PMID- 28743011
TI  - Posterior parietal cortex.
AB  - The posterior parietal cortex, along with temporal and prefrontal cortices, is
      one of the three major associative regions in the cortex of the mammalian brain.
      It is situated between the visual cortex at the caudal pole of the brain and the
      somatosensory cortex just behind the central sulcus. Technically, any cortex
      covered by the parietal bone is referred to as 'parietal cortex', but the
      posterior sector, formally referred to as posterior parietal cortex, is indeed
      its own functional section of cortex, consisting of Brodmann's areas 5, 7, 39,
      and 40 in humans, areas 5 and 7 in macaques, and area 7 in rodents (Figure 1).
      Whereas the anterior parietal cortex in humans comprises primary somatosensory
      areas, the posterior parietal cortex has several higher-order functions. It is
      referred to as an 'associative' cortical region because it is neither strictly
      sensory nor motor, but combines inputs from a number of brain areas including
      somatosensory, auditory, visual, motor, cingulate and prefrontal cortices, and it
      integrates proprioceptive and vestibular signals from subcortical areas.

PMID- 28743012
TI  - Size constancy following long-term visual deprivation.
AB  - We can estimate the veridical size of nearby objects reasonably well irrespective
      of their viewing distance. This perceptual capability, termed size constancy, is
      accomplished by combining information about retinal image size together with the
      viewing distance, or using the relational information available in the scene, via
      direct perception [1]. A previous study [2] showed that children typically
      underestimate the size of a distant object. This underestimation is reduced with
      time, suggesting that years of visual experience may be essential for attaining
      true size constancy. But what if you have had very limited vision during the
      early years of life? We studied 23 Ethiopian children suffering from bilateral,
      early-onset cataract, who were surgically treated only years after birth.
      Surprisingly, most children were able to estimate object size reasonably well
      irrespective of distance; in fact, they usually tended to overestimate the far
      object size. Closer examination indicated that, although before surgery the
      patients were diagnosed as having a full, mature bilateral cataract, they
      nevertheless had some residual form of vision, typically limited to very close
      range. Gandhi et al.[3] earlier reported immediate susceptibility to geometric
      visual illusions in a similar group of newly-sighted children, concluding that
      size constancy was probably innate. We suggest that their immediate ability to
      judge physical size irrespective of distance is more likely to result from their
      previous visual experience.

PMID- 28743013
TI  - Phototransduction in fan worm radiolar eyes.
AB  - Fan worms (Annelida: Sabellidae) are sessile polychaetes that spend their adult
      lives in tubes and project their fans, composed of radiolar tentacles, up into
      the water column for respiration and filter feeding. To protect the fan from
      predation, many species have evolved unique compound eyes on the radioles that
      function as shadow or motion detectors, eliciting a rapid withdrawal response in
      reaction to encroaching objects in the water column [1,2]. The structure of the
      eyes, their complexity, and their arrangements on the radioles are very diverse
      among sabellid genera [3] and they display many characteristics atypical of
      polychaete eyes, such as ciliary photoreceptors [3,4] that hyperpolarize in
      response to illumination [5]. Here we examine the retinal transcriptome of the
      radiolar eyes from the fan worm Megalomma interrupta. We find that the opsin, the
      protein component of light sensitive visual pigments, and other phototransduction
      cascade signaling proteins expressed in these eyes are related to those commonly
      associated with vertebrate ciliary photoreceptors, as opposed to the rhabdomeric
      receptors found in the primary eyes of many invertebrates. With previous
      anatomical and physiological observations, these results suggest that the
      radiolar eyes arose independently in fan worms.

PMID- 28743014
TI  - Stable individual signatures in object localization.
AB  - Perceptual processes in human observers vary considerably across a number of
      domains, producing idiosyncratic biases in the appearance of ambiguous figures
      [1], faces [2], and a number of visual illusions [3-6]. This work has largely
      emphasized object and pattern recognition, which suggests that these are more
      likely to produce individual differences. However, the presence of substantial
      variation in the anatomy and physiology of the visual system [4,7,8] suggests
      that individual variations may be found in even more basic visual tasks. To
      support this idea, we demonstrate observer-specific biases in a fundamental
      visual task - object localization throughout the visual field. We show that
      localization judgments of briefly presented targets produce idiosyncratic
      signatures of perceptual distortions in each observer and suggest that even the
      most basic visual judgments, such as object location, can differ substantially
      between individuals.

PMID- 28743015
TI  - Plant Domestication: Wild Date Palms Illuminate a Crop's Sticky Origins.
AB  - In a new study, previously unknown populations of wild date palm have been
      identified in remote areas of Oman. Genomic analyses indicate date palm
      domestication occurred in the eastern portion of the Arabian Peninsula and reveal
      substantial subsequent gene flow with African palm populations.

PMID- 28743016
TI  - Human Development: Faces in the Womb.
AB  - In the first day of life, infants respond specifically to the crude configuration
      of a human face. New research finds that this visual sensitivity is present even
      in the weeks before birth.

PMID- 28743017
TI  - Development: Pubertal Hormones Meet the Adolescent Brain.
AB  - At the onset of puberty, ovarian hormones increase inhibitory tone in the
      prefrontal cortex. Inhibitory maturation is a hallmark of the initiation of
      developmental windows of neural plasticity; pubertal hormones may trigger the
      opening of an adolescent critical period for experience-dependent rewiring of
      circuits underlying executive function.

PMID- 28743018
TI  - Zoology: Molluscs All Beneath the Sun, One Shell, Two Shells, More, or None.
AB  - One great remaining problem in evolutionary biology is to understand which common
      ancestor could have given rise to descendants as different as giant squid and
      microscopic pea clams. Two new papers provide important insights into molluscan
      body plan disparity.

PMID- 28743019
TI  - Motion Vision: Cortical Preferences Influenced by Retinal Direction Selectivity.
AB  - A recent study shows that retinal direction selectivity influences a subset of
      cells in primary visual cortex which respond to the optic flow associated with
      forward motion, while other cortical direction selective cells perform this
      computation independently.

PMID- 28743020
TI  - Animal Communication: When I'm Calling You, Will You Answer Too?
AB  - Male moths compete to arrive first at a female releasing pheromone. A new study
      reveals that additional pheromone cues released only by younger females may
      prompt males to avoid them in favor of older but more fecund females.

PMID- 28743021
TI  - Evolution: An Irresistibly Clear View of Land.
AB  - Visually guided predation is range-limited in water, but works over long
      distances on land. This may have driven our last aquatic ancestors to evolve
      large eyes on the top of their head for spotting crunchy meals on ancient
      riverbanks.

PMID- 28743022
TI  - Neural Evolution: Homology in Neuronal Networks.
AB  - Do behaviors and neuronal networks that control them evolve together in lockstep,
      or do separate selection processes lead to their evolution? New research,
      dissecting the swim motor networks in two related nudibranch species, seeks to
      answer this question.

PMID- 28743023
TI  - Principles of Transgenerational Small RNA Inheritance in Caenorhabditis elegans.
AB  - Examples of transgenerational inheritance of environmental responses are rapidly
      accumulating. In Caenorhabditis elegans nematodes, such heritable information
      transmits across generations in the form of RNA-dependent RNA polymerase
      amplified small RNAs. Regulatory small RNAs enable sequence-specific gene
      regulation, and unlike chromatin modifications, can move between tissues, and
      escape from immediate germline reprogramming. In this review, we discuss the path
      that small RNAs take from the soma to the germline, and elaborate on the
      mechanisms that maintain or erase parental small RNA responses after a specific
      number of generations. We focus on the intricate interactions between heritable
      small RNAs and histone modifications, deposited on specific loci. A trace of
      heritable chromatin marks, in particular trimethylation of histone H3 lysine 9,
      is deposited on RNAi-targeted loci. However, how these modifications regulate
      RNAi or small RNA inheritance was until recently unclear. Integrating the very
      latest literature, we suggest that changes to histone marks may instigate
      transgenerational gene regulation indirectly, by affecting the biogenesis of
      heritable small RNAs. Inheritance of small RNAs could spread adaptive ancestral
      responses.

PMID- 28743024
TI  - A Method to Evaluate the Quality of Clinical Gene-Panel Sequencing Data for
      Single-Nucleotide Variant Detection.
AB  - Customized gene-panel tests, based on next-generation sequencing, have
      demonstrated their usefulness in a plethora of clinical settings. As with other
      clinical diagnostic techniques, gene-panel sequencing for clinical purposes
      requires precise quality control (QC) measures to ensure its reliability. Only
      detected variants are currently recorded in clinical reports; however,
      identifying whether a nondetected variant is a true or false negative is regarded
      essential in a clinical setting and, thus, a comprehensive QC measure is in
      demand. Conventional QC metrics, such as mean coverage and uniformity, are
      considered inadequate for such an evaluation. As such, a more specific measure
      focused on clinically important variants is herein proposed. In this study, we
      suggest a new scoring method for assessing the quality of clinical gene-panel
      sequencing data, specifically for the detection of a set of single-nucleotide
      variants. The performance of the method was analyzed using 2295 clinical samples
      (1012 formalin-fixed, paraffin-embedded and 1283 fresh-frozen tissues), and was
      shown to provide additional information that conventional methods do not show,
      such as mean depth and uniformity. Customized sequencing protocols, which include
      QC criteria, have been optimized by each genomic laboratory. The pass rate
      scoring method proposed in this study provides an appropriate QC response
      variable for the customized panel, which strengthens the reliability of calls on
      clinically relevant variants implicated in clinical reports.

PMID- 28743025
TI  - RNA polymerase I and III: similar yet unique.
AB  - The majority of non-protein-coding RNAs present in eukaryotic cells comprises
      rRNAs, tRNAs and U6 snRNA that are involved in protein biosynthesis and are
      synthesized by DNA-dependent-RNA polymerase I and III. The transcription cycle
      (initiation, elongation and termination) has similar principles in all three
      nuclear RNA polymerases with specific features that are reflected back in their
      structures. Recently, owing to the 'resolution revolution' in electron cryo
      microscopy, there has been a significant advancement in the understanding of
      these molecular machines. Here, we highlight the structure-function adaptation in
      specificity and activity of these molecular machines and present parallels and
      distinctions between their transcription mechanisms.

PMID- 28743026
TI  - Evaluation of the iVET(r) birth monitoring system in primiparous dairy heifers.
AB  - The objective was to validate the iVET(r) birth monitoring system and to
      determine if it reduced fetal death in primiparous dairy heifers over a 1-y
      interval. There were 359 pregnant heifers enrolled; 167 heifers in the iVET(r)
      group were monitored electronically and the remaining 192 (controls) were
      monitored visually for onset of Stage 2 labor, according to routine farm
      management. In addition, as a reference, all heifers were observed throughout the
      study by two independent investigators. Calves born dead or that died within 24 h
      after birth were defined as stillborn. The interval from appearance of the
      chorioallantoic sac to recognition of onset of calving in the control group
      averaged 21 min longer than the iVET(r) signal (p = 0.0001) and rate of fetal
      death was numerically lower in the iVET(r) group (8.9%) than in the control group
      (10.4%, p = 0.65). Interestingly, dystocia occurred more often in the iVET(r)
      group (58.3%) than in the control group (40.9%, p = 0.001). The iVET(r) system
      detected onset of Stage 2 labor earlier than conventional monitoring by farm
      staff. However, the device was lacking in several aspects and should be improved
      before its use in primiparous heifers can be recommended.

PMID- 28743027
TI  - Impact of heat stress on estrus expression and follicle size in estrus under
      field conditions in dairy cows.
AB  - The objective of this study was to investigate the impact of heat stress on the
      expression of estrus signs and follicular diameter at the day of estrus in dairy
      cows under farm conditions. Cows reported in estrus (i.e., by an automated
      activity monitoring system or by the herd manager) were examined by a
      veterinarian. Uterine contractility and the largest diameter of all ovarian
      structures was determined by transrectal palpation and ultrasonography,
      respectively. The amount of estrus discharge, mounting traces and the color of
      the vaginal mucosa were determined in an external examination and scored on 3
      point scales. Blood samples were obtained for analysis of serum progesterone
      concentrations. Cows with a high uterine contractility and high amount of estrus
      discharge were 4.05 and 1.72 times more likely to have an estrus follicle (large,
      presumptive preovulatory follicle >= 12 mm) than cows expressing low amount of
      the estrus sign, respectively. The likelihood for a pink vaginal mucosa, clear
      stringy estrus discharge and mounting traces at the cows back decreased
      continuously with increasing temperature-humidity index (THI) at the day of
      estrus. The likelihood for a serum progesterone concentration < 1 ng/ml at the
      day of estrus decreased continuously with increasing THI >=74. Follicular size
      decreased 0.1 mm for each incremental THI point at the day of estrus. The results
      of this study indicate, that heat stress at the day of estrus significantly
      reduces the intensity of external estrus signs and the size of estrus follicle
      decreases with increasing THI.

PMID- 28743028
TI  - Enhanced photo-electrochemical response of reduced graphene oxide and C3N4
      nanosheets for rutin detection.
AB  - Herein, a sensitive photo-electrochemical sensor based on C3N4 and reduced
      graphene oxide nanosheets modified glassy carbon electrode (C3N4-RGO/GCE) has
      been fabricated for the detection of rutin under UV light illumination. In C3N4
      RGO catalyst, RGO not only works as a template but also promotes electron
      transfer, meanwhile, C3N4 acts as a photocatalyst. Benefiting from the superior
      electron transfer capacity and efficient UV light effect of the C3N4-RGO
      catalyst, we get a photo-electrochemical sensor for the rutin detecting with a
      low detection limit of 1.78*10-9molL-1 and an excellent linear range of 5*10-9
      1.4*10-4molL-1. Meanwhile, the achieved C3N4-RGO/GCE demonstrated nice
      selectivity, good reproducibility as well as reliable stability. Moreover,
      compared with the electrochemical determination, the C3N4-RGO electrode provides
      a new way for rutin detection by photo-electrochemical method with a promising UV
      light responsive result.

PMID- 28743029
TI  - Thermoresponsive nanoparticle agglomeration/aggregation in salt solutions:
      Dependence on graft density.
AB  - Gold nanoparticles with a graft density of 0.09, 0.30 and 0.40chains/nm2 of
      poly(N-isopropylacrylamide) were reproducibly synthesized by varying the ratio of
      disulfide terminated poly(N-isopropylacrylamide) to gold nanoparticle. The
      polymer coated nanoparticles were stable at room temperature in 50mM NaCl, yet
      agglomerated at 37 degrees C. Previous studies have observed conflicting results
      as to the reversibility of this agglomeration. Particle agglomeration with three
      different graft densities was studied in 50mM NaCl by measurements of their
      localized surface plasmon resonance and hydrodynamic diameter, and imaging with
      electron microscopy. Agglomerates with a polymer graft density of 0.30 and
      0.40chains/nm2 could be dispersed with sonication, while particles with a graft
      density of 0.09chains/nm2 irreversibly aggregated. The graft density dependence
      on whether agglomeration or aggregation occurred is due to changes in collapsed
      polymer steric effects. Localized surface plasmon resonance measurements of
      agglomerates were discordant with hydrodynamic diameter measurements in
      determining agglomeration reversibility, which shed light on reasons previous
      reports yielded different interpretations on the reversibility of this
      agglomeration. This work demonstrates how polymer graft density affects
      thermoresponsive nanoparticle stability in salt solutions and the need for use of
      complementary techniques when determining agglomeration.

PMID- 28743030
TI  - Reactive CeO2 nanofluids for UV protective films.
AB  - We investigate surface modification by organo-trimethoxysilanes of nano-ceria and
      if such surface-modified nano-ceria can be transformed into solvent-free
      nanofluids. We also examine whether simultaneous modification with ionic liquid
      salts and with acrylate groups yields nanofluids suitable for forming UV
      protective films and clear coatings by UV-initiated polymerization. Nominally 3nm
      diameter CeO2 was successfully synthesized and surface decorated with an ionic
      liquid salt and with acrylate groups to produce a core/shell structured solvent
      free nanofluid after ion exchange of chloride for a soft polyoxyethylene
      sulfonate anion. This room temperature nanofluid melts at about -10 degrees C and
      exhibits a glass transition at about -71 degrees C. The melting enthalpy, about
      19J/g, corresponds approximately to the gain in surface free energy of such
      nanofluid particles upon transforming from the solid state to liquid state.
      Robust films were made by UV photoinitiation of this nanofluid in combination
      with ethylene glycol dimethacrylate and with a polyoxyethylene diacrylate to
      yield cross-linked films with absorption coefficients alpha350nm=6.6+/-0.8cm2/mg
      and alpha300nm=24.5+/-3.5cm2/mg. Average near UV protection over 300-350nm of 1-3
      optical density units can be obtained with 0.065-0.19mg/cm2 of CeO2. These
      materials appear almost three-fold more effective, per unit ceria, than
      previously reported clearcoats of nanoceria.

PMID- 28743031
TI  - High pH thresholding of beef with VNIR hyperspectral imaging.
AB  - Initial quality grading of meat is generally carried out using invasive and
      occasionally destructive sampling for the purposes of pH testing. Precise pH and
      thresholds exist to allow the classification of different statuses of meat, e.g.
      for detection of dry, firm, and dark (DFD) (when dealing with cattle and sheep),
      or pale, soft exudative meat (when dealing with pork). This paper illustrates
      that threshold detection for pH level in beef with different freshness levels
      (fresh, fresh frozen-thawed, matured, and matured frozen-thawed). Use of support
      vector machine (SVM) analysis allowed for the classification of beef samples with
      a pH above 5.9, and below 5.6, with an accuracy of 91% and 99% respectively.
      Biochemical and physical conditions of the meat concerning the pH are discussed.

PMID- 28743032
TI  - STRAF-A convenient online tool for STR data evaluation in forensic genetics.
AB  - Population data in forensic genetics has to be checked for a variety of
      statistical parameters before it can be employed for case work. A lot of very
      powerful statistical tools are available for this task, most of them developed by
      labs having their research focus on population genetics or evolution. However,
      most of these programs require a substantial amount of experience. In addition,
      to our knowledge, none of the freely available programs calculates all the common
      parameters for a population study in forensic genetics at once, based on a single
      input file. We present here a convenient online tool that fills this gap. STRAF
      (STR Analysis for Forensics) provides an intuitive interface and input file
      format and computes all the relevant parameters for a classical population study
      based on autosomal STR data at once and in a convenient way. In addition, STRAF
      includes a PCA module that can be used for population substructure detection or
      quality control. The results generated by the program were verified by
      recalculating parameters from an already published population study.

PMID- 28743033
TI  - Analysis of the genetic structure of the Malay population: Ancestry-informative
      marker SNPs in the Malay of Peninsular Malaysia.
AB  - Malay, the main ethnic group in Peninsular Malaysia, is represented by various
      sub-ethnic groups such as Melayu Banjar, Melayu Bugis, Melayu Champa, Melayu
      Java, Melayu Kedah Melayu Kelantan, Melayu Minang and Melayu Patani. Using data
      retrieved from the MyHVP (Malaysian Human Variome Project) database, a total of
      135 individuals from these sub-ethnic groups were profiled using the Affymetrix
      GeneChip Mapping Xba 50-K single nucleotide polymorphism (SNP) array to identify
      SNPs that were ancestry-informative markers (AIMs) for Malays of Peninsular
      Malaysia. Prior to selecting the AIMs, the genetic structure of Malays was
      explored with reference to 11 other populations obtained from the Pan-Asian SNP
      Consortium database using principal component analysis (PCA) and ADMIXTURE.
      Iterative pruning principal component analysis (ipPCA) was further used to
      identify sub-groups of Malays. Subsequently, we constructed an AIMs panel for
      Malays using the informativeness for assignment (In) of genetic markers, and the
      K-nearest neighbor classifier (KNN) was used to teach the classification models.
      A model of 250 SNPs ranked by In, correctly classified Malay individuals with an
      accuracy of up to 90%. The identified panel of SNPs could be utilized as a panel
      of AIMs to ascertain the specific ancestry of Malays, which may be useful in
      disease association studies, biomedical research or forensic investigation
      purposes.

PMID- 28743034
TI  - Therapeutic advances in musculoskeletal AAV targeting approaches.
AB  - The use of recombinant adeno-associated viruses (rAAVs) is highly prevalent in
      musculoskeletal gene therapies due to their versatility, high transduction
      efficiency, natural tropism and vector genome persistence for years. As the
      largest organ in the body, treatment of skeletal muscle for widespread and
      sufficient therapeutic gene expression is highly challenging. In addition to
      disease-specific hurdles, vector genome loss, off-target gene transfer and immune
      responses to treatment can diminish the overall benefit of rAAV therapies. A
      variety of approaches have been developed to overcome these challenges and
      improve musculoskeletal targeting of rAAVs. This review focuses on recent
      advancements and remaining obstacles in creating optimal rAAV-based therapies for
      musculoskeletal application.

PMID- 28743035
TI  - Current trials to reduce surgical intervention in ductal carcinoma in situ of the
      breast: Critical review.
AB  - The high proportion of ductal carcinoma in situ (DCIS) presented in mammographic
      screening and the relatively low risk of progression to invasive disease have
      raised questions related to overtreatment. Following a review of current DCIS
      management protocols a more conservative approach has been suggested. Clinical
      trials have been introduced to evaluate the option of avoiding surgical
      intervention in a proportion of patients with DCIS defined as "low-risk" using
      certain clinicopathological criteria. These trials can potentially provide
      evidence-based models of active surveillance (with or without endocrine therapy)
      as a future management approach. Despite the undisputable fact of our need to
      address the obvious overtreatment of screen-detected DCIS, some important
      questions need to be considered regarding these trials including the eligibility
      criteria and definition of risk, the proportion of patient eligible for
      inclusion, and the length of time required for proper analysis of the trials'
      outcome in view of the long-term natural history of DCIS progression particularly
      the low-risk group. These factors can potentially affect the practicality and
      future impact of such trials. This review provides critical analysis of current
      DCIS management trials and highlights critical issues related to their
      practicality and the expected outcome.

PMID- 28743036
TI  - RECIST response and variation of circulating tumour cells in phase 1 trials: A
      prospective multicentric study.
AB  - BACKGROUND: Circulating tumour cell (CTC) counting could be a new biomarker for
      better evaluation of tumour response to molecules tested in phase I trials.
      PATIENTS AND METHODS: Consenting patients with advanced metastatic cancer
      referred to various phase I units were enrolled prospectively in this study. CTCs
      from 7.5 ml of whole blood drawn at baseline and after starting experimental
      therapy were counted using the CellSearch system, and tumour response was
      assessed using RECIST 1.1 criteria at baseline and 2 months after treatment
      initiation. RESULTS: Between March 2010 and May 2013, a total of 326 patients
      were enrolled, among whom 214 were evaluable (49% male, median age = 56; main
      cancer types: lung [28], colon [53], ovarian [18], breast [28]). At baseline, we
      detected >=1 CTC/7.5 ml in 113/214 patients (53%), and at day 30, we observed >=1
      CTC/7.5 ml in 103/214 patients (48%). Two months after treatment initiation, 11
      (5%) of the 214 patients were classified as having a partial response, with no
      CTCs in 9 of them or a decrease in the CTC count after therapy. In contrast,
      among the 104 patients (49%) classified as having progressive disease, 38
      patients had a higher CTC count. The remaining 99 patients (49%), 33 of whom
      (33%) had a lower CTC count, were classified as having stable disease. The
      sensitivity and specificity of CTC variation for predicting progressive disease
      were 41% (32-51%) and 80% (73-88%) respectively. CONCLUSION: An early CTC change
      following therapy does not correlate with RECIST response in patients with
      advanced cancer enrolled in phase I trials.

PMID- 28743037
TI  - Exogenous applications of Polyamines modulate drought responses in wheat through
      osmolytes accumulation, increasing free polyamine levels and regulation of
      polyamine biosynthetic genes.
AB  - Polyamines (PAs) can improve drought stress tolerance in plants; however, very
      limited information is available on the mechanism of action of exogenous
      application by different methods under drought stress in wheat. The present study
      investigates the mechanism through which seed priming and foliar spraying with
      PAs protect wheat plants from drought stress. 10 days old wheat seedlings were
      exposed to drought stress by withholding water alone or with 100 MUM PAs
      solutions (putrescine, Put; spermine, Spm; and mixture of Put and Spm for 10 h
      seed-priming or three foliar sprays during withholding water. Drought stress
      impaired the wheat growth and altered the osmoprotectants, endogenous PAs levels,
      PAs biosynthetic genes expression and weight of 1000 grains compared to the
      corresponding control values. Exogenously applied PAs improved cell water status,
      accumulated osmoprotectants and PAs and up-regulated PAs biosynthetic genes, ADC,
      arginine decarboxylase; DHS, deoxyhypusine synthase; ODC, ornithine decarboxylase
      and SAMDC, S-adenosyl methionine decarboxylase. Put significantly regulate the
      endogenous PAs by both methods of application, however, Spm and mixture of Put
      and Spm could positively regulate the endogenous PAs and the biosynthetic gene
      expression by foliar spraying rather than seed priming. The data provide evidence
      that maintenance of water economy through stabilized cellular structure is an
      important strategy of drought tolerance by PAs in wheat.

PMID- 28743038
TI  - Physiological, vascular and nanomechanical assessment of hybrid poplar leaf
      traits in micropropagated plants and plants propagated from root cuttings: A
      contribution to breeding programs.
AB  - Micropropagated plants experience significant stress from rapid water loss when
      they are transferred from an in vitro culture to either greenhouse or field
      conditions. This is caused both by inefficient stomatal control of transpiration
      and the change to a higher light intensity and lower humidity. Understanding the
      physiological, vascular and biomechanical processes that allow micropropagated
      plants to modify their phenotype in response to environmental conditions can help
      to improve both field performance and plant survival. To identify changes between
      the hybrid poplar [Populus tremula * (Populus * canescens)] plants propagated
      from in vitro tissue culture and those from root cuttings, we assessed leaf
      performance for any differences in leaf growth, photosynthetic and vascular
      traits, and also nanomechanical properties of the tracheary element cell walls.
      The micropropagated plants showed significantly higher values for leaf area, leaf
      length, leaf width and leaf dry mass. The greater leaf area and leaf size
      dimensions resulted from the higher transpiration rate recorded for this stock
      type. Also, the micropropagated plants reached higher values for chlorophyll a
      fluorescence parameters and for the nanomechanical dissipation energy of
      tracheary element cell walls which may indicate a higher damping capacity within
      the primary xylem tissue under abiotic stress conditions. The performance of the
      plants propagated from root cuttings was superior for instantaneous water-use
      efficiency which signifies a higher acclimation capacity to stressful conditions
      during a severe drought particularly for this stock type. Similarities were found
      among the majority of the examined leaf traits for both vegetative plant origins
      including leaf mass per area, stomatal conductance, net photosynthetic rate,
      hydraulic axial conductivity, indicators of leaf midrib vascular architecture, as
      well as for the majority of cell wall nanomechanical traits. This research
      revealed that there were no drawbacks in the leaf physiological performance which
      could be attributed to the micropropagated plants of fast growing hybrid poplar.

PMID- 28743039
TI  - Exogenous application of poly-gamma-glutamic acid enhances stress defense in
      Brassica napus L. seedlings by inducing cross-talks between Ca2+, H2O2,
      brassinolide, and jasmonic acid in leaves.
AB  - Poly-gamma-glutamic acid (gamma-PGA) is a microbe-secreted isopeptide shown to
      promote growth and enhance crop stress tolerance. However, its downstream
      signaling pathways are unknown. Here, we studied gamma-PGA-induced tolerance to
      salt and cold stresses. Pretreatment with gamma-PGA contributed to enhance stress
      tolerance of canola seedlings by promoting proline accumulation and total
      antioxidant capacity (T-AOC) improvement. Further, Ca2+, H2O2, brassinolide, and
      jasmonic acid were found to be involved in the gamma-PGA-induced process. First,
      using signal blockers, we concluded that gamma-PGA activated Ca2+ fluctuations in
      canola seedling leaves. Second, the activated Ca2+ further elicited H2O2
      production by Ca2+-binding proteins CBL9, CPK4, and CPK5. Third, the H2O2 signal
      promoted brassinolide and jasmonic acid biosynthesis by upregulating key genes
      (DWF4 and LOX2, respectively) for synthesizing these compounds. Lastly,
      brassinolide and jasmonic acid increased H2O2 which promoted proline accumulation
      and T-AOC improvement and further enhanced Ca2+-binding proteins including CaM,
      CBL10, and CPK9.

PMID- 28743041
TI  - Prospects for engineering and improvement of cross-protective virus strains.
AB  - Mild strain cross-protection is currently an important method for the production
      of high quality plant products; despite challenge from severe virus isolates the
      initial protecting strain precludes symptom development. The mechanism of cross
      protection is not yet resolved as RNA silencing does not sufficiently explain the
      phenomenon. Six requirements have been put forward to ensure long-lasting
      protection. We propose two additional requirements for effective and durable mild
      strain cross-protection; mild strains based on knowledge of the mechanism and
      consideration of impacts to consumers. Future research on predicting phenotype
      from genotype and understanding virus-plant and virus-vector interactions will
      enable improvement of cross-protective strains. Shared international databases of
      whole ecosystem interactions across a wide range of virus patho- and symbiotic
      systems will form the basis for making step-change advances towards our
      collective ability to engineer and improve mild strain cross-protection.

PMID- 28743040
TI  - Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental
      phenotypes.
AB  - Prenatal exposure to organophosphorus pesticides (OPs) has been associated with
      different neurodevelopmental outcomes across different cohorts. A phenotypic
      approach may address some of these differences by incorporating information
      across scales and accounting for the complex correlational structure of
      neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can
      account for confounding by collinear co-exposures. We use this framework to
      examine associations between prenatal exposure to OPs and behavior, executive
      functioning, and IQ assessed at age 6-9 years in a cohort of 404 mother/infant
      pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with
      a factor analysis, and estimated associations between OP metabolites and these
      phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven
      factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3)
      Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and
      7) Verbal Intelligence. These, along with the Working Memory Index, were
      standardized and scaled so that positive values reflected positive attributes and
      negative values represented adverse outcomes. Standardized dimethylphosphate
      metabolites were negatively associated with Internalizing factor scores (beta^ -
      0.13, 95% CI - 0.26, 0.00) but positively associated with Executive Functioning
      factor scores (beta^ 0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate
      metabolites were negatively associated with the Working Memory Index (beta^ -
      0.17, 95% CI - 0.33, - 0.03). Associations with factor scores were generally
      stronger and more precise than associations with individual instrument-specific
      items. Factor analysis of outcomes may provide some advantages in etiological
      studies of childhood neurodevelopment by incorporating information across scales
      to reduce dimensionality and improve precision.

PMID- 28743042
TI  - Clinical outcome and rehabilitation of homeless mentally ill patients admitted in
      mental health institute of South India: "Know the Unknown" project.
AB  - OBJECTIVES: Homeless Mentally Ill (HMI) patients represent a unique global
      problem and pose a challenge in treatment, management and rehabilitation
      services. There is sparse data on HMI patients in India. The objective of this
      paper is to study the clinical outcome and rehabilitation of HMI patients.
      METHODS: We performed a retrospective chart review of 'HMI' patients from 1st
      January 2002 to 31st December 2015, who were admitted under Department of
      Psychiatry at National Institute of Mental Health and Neurosciences (NIMHANS),
      Bangalore, India. Clinical outcomes were analysed by descriptive statistics and
      predictors of family reintegration were analysed by logistic regression model.
      RESULTS: Seventy-eight HMI (unknown) patients were admitted in fourteen years
      period. 64(82%) were improved at discharge, 40(51.3%) were reintegrated to the
      family; 15(19.2%) were sent to state home for women, and 17(21.8%) were sent to
      Non-Governmental Organization (NGO)/Rehabilitation Centre and 6 (7.8%) required
      multispecialty care in general hospital or absconded from the hospital during
      inpatient care. The logistic regression model showed that mental retardation (B=
      2.204, P=0.002) was negatively correlated with family reintegration and clinical
      improvement at discharge (B=2.373, P=<0.001) was positively correlated with
      family reintegration. CONCLUSIONS: In our study majority of HMI patients improved
      at the time of discharge. Family reintegration was possible in about half of HMI
      patients after treatment. Mental retardation and clinical improvement are
      important predictors of family reintegration of HMI patients.

PMID- 28743043
TI  - Neurotrophy and immunomodulation of induced neural stem cell grafts in a mouse
      model of closed head injury.
AB  - Closed head injury (CHI) usually results in severe and permanent neurological
      impairments, which are caused by several intertwined phenomena, such as cerebral
      edema, blood-brain barrier (BBB) disruption, neuronal loss, astroglial scarring
      and inflammation. We previously reported that induced neural stem cells (iNSCs),
      similar to neural stem cells (NSCs), can accelerate neurological recovery in vivo
      and produce neurotrophic factors in vitro. However, the effects of iNSC
      neurotrophy following CHI were not determined. Moreover, whether iNSCs have
      immunomodulatory properties is unknown. Mouse models of CHI were established
      using a standardized weight-drop device and assessed by neurological severity
      score (NSS). Although these models fail to mimic the complete spectrum of human
      CHI, they reproduce impairment in neurological function observed in clinical
      patients. Syngeneic iNSCs or NSCs were separately transplanted into the brains of
      CHI mice at 12h after CHI. Neurological impairment post-CHI was evaluated by
      several tests. Animals were sacrificed for morphological and molecular biological
      analyses. We discovered that iNSC administration promoted neurological functional
      recovery in CHI mice and reduced cerebral edema, BBB disruption, cell death and
      astroglial scarring following trauma. Implanted iNSCs could up-regulate brain
      derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF)
      levels to support the survival of existing neurons after CHI. In addition,
      engrafted iNSCs decreased immune cell recruitment and pro-inflammatory cytokine
      expression in the brain post-injury. Moreover, we found significant nuclear
      factor-kappaB (NF-kappaB) inhibition in the presence of iNSC grafts. In short,
      iNSCs exert neurotrophic and immunomodulatory effects that mitigate CHI-induced
      neurological impairment.

PMID- 28743044
TI  - Electrophysiological and gene expression characterization of the ontogeny of
      nestin-expressing cells in the adult mouse midbrain.
AB  - The birth of new neurons, or neurogenesis, in the adult midbrain is important for
      progressing dopamine cell-replacement therapies for Parkinson's disease. Most
      studies suggest newborn cells remain undifferentiated or differentiate into glia
      within the adult midbrain. However, some studies suggest nestin+neural precursor
      cells (NPCs) have a propensity to generate new neurons here. We sought to confirm
      this by administering tamoxifen to adult NesCreERT2/R26eYFP transgenic mice,
      which permanently labelled adult nestin-expressing cells and their progeny with
      enhanced yellow fluorescent protein (eYFP). eYFP+ midbrain cells were then
      characterized 1-32weeks later in acutely prepared brain slices using whole-cell
      patch clamp electrophysiology combined with single-cell RT-qPCR. Most eYFP+ cells
      exhibited a mature neuronal phenotype with large amplitude fast action potentials
      (APs), spontaneous post-synaptic currents (sPSCs), and expression of 'mature'
      neuronal genes (NeuN, Gad1, Gad2 and/or VGLUT2). This was the case even at the
      earliest time-point following tamoxifen (i.e. 1week). In comparison to
      neighboring eYFP- (control) cells, eYFP+ cells discharged more APs per unit
      current injection, and had faster AP time-to-peak, hyperpolarized resting
      membrane potential, smaller membrane capacitance and shorter duration sPSCs.
      eYFP+ cells were also differentiated from eYFP- cells by increased expression of
      'immature' pro-neuronal genes (Pax6, Ngn2 and/or Msx1). However, further analyses
      failed to reveal evidence of a place of birth, neuronal differentiation,
      maturation and integration indicative of classical neurogenesis. Thus our
      findings do not support the notion that nestin+NPCs in the adult SNc and midbrain
      generate new neurons via classical neurogenesis. Rather, they raise the
      possibility that mature neurons express nestin under unknown circumstances, and
      that this is associated with altered physiology and gene expression.

PMID- 28743045
TI  - Wind friction parametrisation used in emission models for wastewater treatment
      plants: A critical review.
AB  - Emission models are widely applied tools for estimating atmospheric emissions
      from wastewater treatment plants (WWTPs). The friction velocity u* is a key
      variable for the modelling of emissions from passive liquid surfaces in WWTPs.
      This work evaluated different parametrisations of u* for passive liquid surfaces
      at the scale of WWTP units, which present relatively small fetches, based on
      available wind friction and wave data measured at wind-wave tanks (fetches
      spanning from approximately 3 to 100 m, and wind speeds from 2 to 17 m s-1). The
      empirical correlation by Smith (1980; J. Phys. Oceanogr. 10, 709-726), which has
      been frequently adopted in air emission models (despite the fact that it was
      originally derived for the ocean) presented a general tendency to overestimate
      u*, with significant (although not extreme) relative errors (mean and maximum
      errors of 13.5% and 36.6%, respectively); the use of Charnock's relation, with
      Charnock constant 0.010, performed in a very similar manner (mean and maximum
      errors of 13.3% and 37.8%, respectively). Better estimates of u* were achieved by
      parametrisations based on the significant wave steepness. Simplified correlations
      between the wind drag and the non-dimensional fetch were obtained. An approach
      was devised, comprising the use of Charnock's relation (with Charnock constant
      0.010) and of these simplified correlations, depending on the ranges of frequency
      of the peak waves, fetch and wind speed. The proposed approach predicted u* with
      improved accuracy (mean, maximum and 95%-percentile relative errors of 6.6%,
      16.7% and 13.9%, respectively), besides being able to incorporate the influence
      of the fetch in the wind drag, thus taking into account the size of the tanks in
      the WWTPs.

PMID- 28743046
TI  - Multi-informant assessment of siblings of youth with autism spectrum disorder:
      Parent-child discrepancies in at-risk classification.
AB  - BACKGROUND: The behavioral and emotional functioning of typically-developing (TD)
      siblings of youth with autism spectrum disorder (ASD) has been frequently
      assessed in the literature; however, these assessments typically include only one
      informant, rarely considering differences between parent and self-reports of
      sibling adjustment. AIMS: This study examined parent-youth reported informant
      discrepancies in behavioral and emotional functioning, including whether parent
      and youth reports yielded the same conclusions regarding TD sibling risk status.
      METHODS, PROCEDURES, AND RESULTS: Among 113 parents and TD siblings of youth with
      ASD, TD siblings self-reported more overall, conduct, hyperactivity, and peer
      problems (compared to parent reports). Although few siblings were considered at
      risk, those who were identified were not usually identified as at-risk on both
      informants' reports. Moreover, ASD symptoms, broader autism phenotype symptoms,
      parent mental health concerns, and social support from parents were all related
      to differences in at-risk classification between parent- and sibling self-report.
      CONCLUSIONS AND IMPLICATIONS: This paper highlights the necessity of multi
      informant reporting when considering TD sibling psychological functioning. WHAT
      THIS PAPER ADDS: This study helps to address gaps in the literature on assessment
      of emotional and behavioral functioning of TD siblings of youth with ASD. The
      results highlight the importance of utilizing both parent- and self-report when
      identifying TD siblings at-risk for maladjustment. Although few siblings were
      considered at-risk, those who were identified were not usually identified as such
      on both informants' reports, and a variety of sibling- and parent-factors were
      associated with differences in at-risk classification. Thus, inclusion and
      examination of both parent- and self-report of TD sibling psychological
      functioning is vital for accurately identifying numbers of TD siblings at-risk of
      maladjustment.

PMID- 28743047
TI  - Bohr effect of human hemoglobin: Separation of tertiary and quaternary
      contributions based on the Wyman equation.
AB  - As a prelude to separating tertiary from quaternary structure contributions to
      the Bohr effect, we employed the Wyman equation to analyze Bohr data for human
      hemoglobin to which 2,3-bisphosphoglycerate, 2,3-BPG, is bound. Changes in the
      pKas of the histidine Bohr groups result in a net reduction of their
      contributions to the Bohr effect at pH 7.4 compared to their contributions in
      stripped hemoglobin. The non-histidine 2,3-BPG binding groups - the beta-chain
      terminal amino group and Lys82beta - make negative and positive contributions,
      respectively, to the Bohr effect. The final result is that the Bohr effect at
      physiological pH is higher for 2,3-BPG bound compared to stripped hemoglobin.
      Contributions linked to His2beta, His77beta and His143beta enable us to separate
      tertiary from quaternary Bohr contributions in stripped and in 2,3-BPG bound
      hemoglobin. Both contributions serve to make the Bohr effect for 2,3-BPG bound
      hemoglobin higher than for stripped hemoglobin at physiological pH.

PMID- 28743048
TI  - The ketogenic diet in patients with myoclonic status in non-progressive
      encephalopathy.
AB  - : Myoclonic status in non-progressive encephalopathy (MSNPE) is characterized by
      the recurrence of long-lasting atypical status epilepticus associated with
      attention impairment and continuous polymorphous jerks, mixed with other complex
      abnormal movements, in infants suffering from a non-progressive encephalopathy.
      The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs
      (AEDs) for patients with refractory epileptic encephalopathies. PURPOSE: In this
      study we assess the efficacy and tolerability of the KD in patients with MSNPE.
      METHODS: Between March 1, 1980 and August 31, 2013, 99 patients who met the
      diagnostic criteria of MSNPE were seen (58 patients in Verona and 41 patients in
      Buenos Aires). Six of these 99 patients were placed on the KD using the Hopkins
      protocol and followed for a minimum period of 24 months. RESULTS: Twelve months
      after initiating the diet, three patients had a 75%-99% decrease in seizures, two
      had a 50%-74% decrease in seizures, and the remaining child had a less than 50%
      seizure reduction. In five patients with a seizure reduction of more than 50%,
      the myoclonic status epilepticus disappeared within 6 months after starting the
      diet. All patients had very good tolerability and no adverse events were
      identified. In most of the patients AEDs were reduced. CONCLUSION: The KD is a
      promising therapy for MSNPE, with most of our patients showing a more than 50%
      seizure reduction. In patients that responded well to the diet cognitive
      performance and quality of life also improved.

PMID- 28743049
TI  - Risk factors for maternal anaemia and low birth weight in pregnant women living
      in rural India: a prospective cohort study.
AB  - OBJECTIVE: The aim of this prospective study was to estimate the prevalence and
      risk factors for maternal anaemia and low birth weight (LBW) in pregnant women
      living in Maharashtra state, India. STUDY DESIGN: This is a prospective study.
      METHODS: Women between 3 and 5 months of pregnancy were recruited from 34
      villages based in Maharashtra state. Baseline data collection, anthropometric
      measurements and blood investigations were performed. Participants were followed
      up to record birth weight. RESULTS: In total, 303 women were eligible, and 287
      (95%) provided data. 77% were anaemic, defined as haemoglobin less than 11.0 g/dl
      at the time of recruitment, with a mean corpuscular volume of 80.5 fl/cell
      (standard deviation: 7.22, range: 53.4-93.8). The increased risk of anaemia was
      seen in women with consanguineous marriages (odds ratio [OR]: 2.41, 95%
      confidence interval [CI]: 1.16-5.01, P = 0.01) after adjustment for potential
      confounding factors. Postdelivery data from full-term singleton live births
      demonstrated a 7% prevalence of LBW. Consanguineous marriage was a major risk
      factor for LBW (OR: 4.10, 95% CI: 1.25-13.41, P = 0.02). The presence of maternal
      anaemia during 3-5 months of pregnancy was associated with lower risk of LBW
      (unadjusted OR: 0.34, 95% CI: 0.13-0.92, P = 0.03). CONCLUSION: About 30% of our
      study participants were in a consanguineous marriage, which was identified as a
      potentially avoidable risk factor for both anaemia and LBW.

PMID- 28743050
TI  - PML-RARalpha stabilized by zinc in human acute promyelocytic leukemia NB4 cells.
AB  - Acute promyelocytic leukemia (APL) is characterized and driven by the
      promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARalpha) fusion
      gene. Previous studies have highlighted the importance of PML-RARalpha
      degradation in the treatment against APL. Considering the presence of two zinc
      fingers in the PML-RARalpha fusion protein, we explored the function of zinc
      homeostasis in maintaining PML-RARalpha stability. We demonstrated for the first
      time that zinc depletion by its chelator N,N,N',N'-tetrakis(2
      pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARalpha degradation in NB4
      APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway.
      In contrast, autophagy protected TPEN-mediated PML-RARalpha degradation in NB4
      APL cells. We further demonstrated that crosstalk between zinc homeostasis and
      nitric oxide pathway played a key role in maintaining PML-RARalpha stability in
      NB4 APL cells. These results demonstrate that zinc homeostasis is vital for
      maintaining PML-RARalpha stability, and zinc depletion by TPEN may be useful as a
      potential strategy to trigger PML-RARalpha degradation in APL cells. We also
      found that TPEN triggered apoptosis of NB4 APL cells in a time-dependent manner.
      The relationship between PML-RARalpha degradation and apoptosis triggered by TPEN
      deserves further study.

PMID- 28743051
TI  - Enhancing women's confidence for physiologic birth: Maternity care providers'
      perspectives.
AB  - OBJECTIVE: The aim of this research study was to explore MCP's beliefs and
      attitudes about physiologic birth and to identify components of antenatal care
      that providers believe may impact a woman's confidence for physiologic labor and
      birth. METHODS: This qualitative descriptive study included maternity care
      providers (N=31) in the Midwestern United States. Providers participated in semi
      structured interviews to describe their beliefs about physiologic birth, their
      role in providing information to women and specific care practices to promote
      women's confidence for physiologic birth. FINDINGS: Six themes emerged including:
      positive beliefs about physiologic birth, trusted relationship with provider,
      woman centered care, education and knowledge, barriers to confidence, and
      antenatal practices to enhance confidence. Variations in beliefs occurred amongst
      providers with different training (i.e., physicians and midwives). CONCLUSION:
      Maternity care providers, including midwives, family physicians and obstetrician
      gynecologists, overwhelmingly support a physiologic approach to labor and birth.
      These providers had a number of suggestions about how antenatal care could be
      enhanced in an effort to increase women's confidence during the antenatal period.
      Supporting physiologic birth is imperative for providers who wish to enhance
      outcomes for mothers and babies.

PMID- 28743052
TI  - Giving birth on our own terms-Women's experience of childbirth at home.
AB  - BACKGROUND: home births are quite rare and are not supported as part of
      mainstream health care services in most European countries. Women who choose home
      as the place of birth often do so because maternity services in hospitals do not
      offer the options that they want. The aim of the present study is to describe
      women's experiences of giving birth at home and to produce a comprehensive
      structure of meaning regarding giving birth at home. DESIGN: a phenomenological
      study based on analysis of open-interview transcripts using Colaizzi's approach.
      PARTICIPANTS: women who gave birth at home FINDINGS: women who have given birth
      at home experience having control over their own body, the care they are given,
      and the practical arrangements surrounding the birth. However, they also
      experience negative attitudes from other people about their decision to give
      birth at home, and challenges because of worries about how they and their baby
      will cope. During the birth women feel a sense of connection to their own body,
      which they trust to tell them what to do. They experience great happiness on
      successfully giving birth and feel connected to nature and the circle of life.
      Being able to celebrate with family members and be pampered by them after the
      birth made the women feel 'like queens'. CONCLUSIONS: women's experience of
      childbirth at home is one of having control over the birthing process and its
      environment. The main challenge is exposure to negative attitudes from others,
      including health care professionals. Overall, the experience was full of
      happiness and good feelings. We conclude that more attention should be paid to
      the quality of birth experiences and women's individual needs and wishes within
      maternity care provision.

PMID- 28743053
TI  - School staff members experience and knowledge in the reporting of potential child
      and youth victimization.
AB  - Victimization has been widely demonstrated to have negative consequences in
      minors. Most crimes against children go unreported and victims tend to reach
      adulthood without receiving any of the available specialized support. Studies
      have highlighted the unique role of school workers in early detection and
      reporting of possible cases of victimization, and have also found high rates of
      underreporting by school staff. The present study analyzes the underreporting of
      child and youth victimization suspicions among school staff and aims to identify
      variables related to its detection and reporting. One hundred and eighty-four
      school staff members (83.7% females, M=42.6years old, SD=11.7) from 17 different
      schools completed a self-administered questionnaire designed to record their
      knowledge and experience regarding the detection and reporting of potential
      victimization cases. Over 74% of the school workers had suspected at least one
      situation of victimization during their careers, but only 27% had actually
      reported these concerns. Higher rates of reporting were significantly associated
      with male gender, more years of experience, and awareness of five common
      misconceptions. Reporting behavior could be predicted by gender, years of
      experience and two statements assessing respondents' knowledge of victimization.
      In order to increase early reporting of possible cases of victimization, it is
      necessary to overcome certain misconceptions, raise awareness among school staff,
      design new training programs or interventions, and adapt the school dynamics in
      the light of these findings.

PMID- 28743054
TI  - Continuity for children after guardianship versus adoption with kin:
      Approximating the right counterfactual.
AB  - Over the past two decades there has been a rapid increase in the number of
      children and youth living in guardianship and adoptive homes who were previously
      in foster care. Further, previous studies compared outcomes for children in
      guardianship homes to those for children in adoptive homes, despite the fact that
      many factors likely affect the selection of foster youth into different types of
      permanent placements. This study examined two counterfactuals for guardianship as
      a permanent placement type: adoption only and adoption or long-term-fostercare
      (A+LTFC). Longitudinal outcomes were tracked for children who exited foster care
      with relatives through guardianship (N=4,884) or adoption (N=12,163), as well as
      children in long-term foster care with relatives (N=4,840). Propensity scores
      were used to match children on key indicators. In the matched sample of
      guardianship versus adoption cases only, children who exited to guardianship were
      more likely to experience discontinuity than children who exited through
      adoption, 11% vs. 6% respectively. However, when guardianship was compared to the
      combination of adoption or long-term foster care, children in guardianship
      experienced the same proportion of discontinuity, 11% vs. 11% respectively. These
      results suggest that simply matching guardianship to adoption without taking into
      account LTFC may be the wrong way to estimate the "what if" counterfactual if
      children were not discharged to guardianship. Findings also support the use of
      guardianship as a potential solution for children in LTFC whose caregivers are
      not planning to adopt.

PMID- 28743055
TI  - The influence of viscous and conducting liquid on the characteristics of the slot
      acoustic wave.
AB  - The influence of the liquid with the different values of conductivity,
      permittivity, and viscosity on the characteristics of the slot mode in the
      structure consisting of delay line with propagating shear - horizontal acoustic
      wave of zero order (SH0) and upper piezoelectric plate separated by the air gap
      was experimentally investigated. The delay line made of the Y-X lithium niobate
      plate 0.2mm thick contained two interdigital transducers for the excitation and
      reception of acoustic wave in the frequency range of 2.6-3.8MHz. The upper plate
      represented the 0.5mm thick plate of Z-X lithium niobate. The excitation of the
      slot mode led to the appearance of the sharp resonant peaks on the frequency
      dependencies of insertion loss and phase of the output signal. It has been found
      that the depth and frequency of these peaks depend on the parameters of liquid
      contacting with the upper plate. The possibility of the use of the slot mode in
      the pointed structure for the identification of liquids with the different values
      of the conductivity, viscosity, and permittivity was shown. The qualitative
      explanations of the obtained experimental results are presented.

PMID- 28743056
TI  - Apigenin attenuates isoflurane-induced cognitive dysfunction via epigenetic
      regulation and neuroinflammation in aged rats.
AB  - PURPOSE OF THE RESEARCH: Post operational cognitive dysfunction (POCD) occurs in
      patients after anesthesia and surgery. Abnormal histone acetylation and
      neuroinflammation are key factors in the pathogenesis of cognitive impairment.
      Apigenin not only has an anti-inflammatory activity but also modifies histone
      acetylation. We aimed to investigate whether apigenin can attenuate isoflurane
      exposure-induced cognitive decline by regulating histone acetylation and
      inflammatory signaling. MATERIALS AND METHODS: Spatial learning and memory were
      assessed by Morris water maze test. Levels of histone acetylation, BDNF and
      downstream signaling, and inflammatory components were analyzed. PRINCIPAL
      RESULTS: Isoflurane exposure in aged rats lead to impaired spatial learning and
      memory. These rats exhibited dysregulated histone H3K9 and H4K12 acetylation,
      which was accompanied by reduced BDNF expression and suppressed BDNF downstream
      signaling pathway. Apigenin restored histone acetylation and BDNF signaling.
      Apigenin also suppressed isoflurane exposure induced upregulation of
      proinflammatory cytokines and NFkappaB signaling pathway. MAJOR CONCLUSIONS:
      Memory impairment induced by isoflurane exposure is associated with dysregulated
      histone acetylation in the hippocampus, which affects BDNF expression and hence
      BDNF downstream signaling pathway. Apigenin recovers cognitive function by
      restoring histone acetylation and suppressing neuroinflammation.

PMID- 28743057
TI  - Does the presence of clinical symptoms of pulmonary embolism affect the outcome
      of patients with deep vein thrombosis?

PMID- 28743058
TI  - Oral nanotherapeutics: Redox nanoparticles attenuate ultraviolet B radiation
      induced skin inflammatory disorders in Kud:Hr- hairless mice.
AB  - The active participation of an anti-inflammatory drug in the biological pathways
      of inflammation is crucial for the achievement of beneficial and therapeutic
      effects. This study demonstrated the development of redox nanoparticles that can
      circulate in the blood at significantly high levels, thus increasing their
      efficacy as an oral treatment against the deleterious effects of reactive oxygen
      species (ROS) in an in vivo inflammatory skin model. To confirm the blood
      bioavailability of the nanoparticles, mice were injected with the nanoparticles
      solution (RNPN) via oral gavage. Using electron spin resonance and radioactive
      labeling techniques, the blood circulation of the redox polymer that forms the
      nanoparticles was confirmed 24 h after oral administration. This contrasted with
      its low molecular weight counterpart (NH2-TEMPO), which peaked 15 min post
      injection and was found to be cleared rapidly within minutes after the peak. We
      then tested its efficacy in the inflammatory skin model. Kud:Hr-hairless mice
      were irradiated with UVB (302 nm) to induce skin damage and inflammation.
      Throughout the entire period of UVB irradiation, RNPN was administered to mice by
      free drinking. NH2-TEMPO was used as the control. The results showed that oral
      supplementation of RNPN significantly improved the therapeutic effects of the
      core nitroxide radical compared with its low molecular weight counterpart.
      Furthermore, RNPN significantly reduced UVB-induced skin aging, epidermal
      thickening, edema, erythema, skin lesions, and various pathological skin
      inflammatory disorders in vivo. From the obtained data, we concluded that the use
      of long-circulating redox nanoparticles (RNPN) provided an effective treatment
      against the damaging effects of excessive ROS in the body.

PMID- 28743059
TI  - Altered connectivity within and between the default mode, central executive, and
      salience networks in obsessive-compulsive disorder.
AB  - BACKGROUND: Default mode network (DMN), central executive network (CEN) and
      salience network (SN) are the three most important intrinsic networks of the
      human brain. Recent studies emphasized the importance of the "triple-network
      model" which illustrated the interactions within and between DMN, CEN and SN in
      the pathophysiology of psychiatric disorders. However, previous studies of
      obsessive-compulsive disorder (OCD) just explored the altered connectivity within
      these networks while neglected the coupling between them. Hence, the present
      study was designed to fill this research gap. METHODS: Resting-state functional
      magnetic resonance imaging (fMRI) data from 35 OCD patients and 32 healthy
      controls (HCs) were acquired. Independent component analysis (ICA) was used to
      extract sub-networks of the DMN, CEN, and SN. Functional connectivity (FC) values
      within and between these networks were measured. RESULTS: OCD patients had
      increased FC within several DMN, CEN, and SN subsystems. In addition, OCD
      patients demonstrated aberrant functional interactions between the SN and
      anterior DMN (aDMN) as well as between the SN and the dorsal CEN (dCEN), and the
      interaction between the SN and dCEN significantly correlated with trait anxiety
      level in the OCD group. LIMITATION: Lack of the assessments of cognitive
      functions is the main limitation of the present study. CONCLUSIONS: Not only
      impaired coupling within the brain core intrinsic large-scale networks, but also
      coupling between large-scale neurocognitive networks, which reflect the
      difficulties in switching between task-negative and task-positive processing
      modes are involved in the neurobiological mechanism of OCD.

PMID- 28743060
TI  - Glucose fluctuation and the resultant endothelial injury are correlated with
      pancreatic beta cell dysfunction in patients with coronary artery disease.
AB  - AIMS: We evaluated whether glucose fluctuation (GF) causes vascular endothelial
      injury and affects glucometabolic factors during lengthy oral glucose tolerance
      test (OGTT). METHODS: We enrolled consecutive 116 patients with coronary artery
      disease (CAD) who were performed coronary angiography and 4-h OGTT. Blood samples
      were collected before and 4h after glucose load to measure endothelial injury
      factor [von Willebrand factor (vWF) and vWF/a disintegrin-like and
      metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) ratio]. GF was
      defined as maximum - minimum blood glucose levels during 4-h OGTT. We estimated
      the relationship between GF and glucometabolic factors. RESULTS: vWV and
      vWF/ADAMTS-13 ratio were significantly correlated with GF during 4-h OGTT. GF was
      significantly correlated with homeostasis model to assess insulin resistance
      (HOMA-IR) (R=0.262), Matsuda index (R=-0.405), insulinogenic index (R=-0.336),
      HbA1c (R=0.281) and disposition index (R=-0.672). When dividing patients into
      impaired and preserved category groups according to the average value of GF
      (122mg/dL), adjusted to age, sex, HOMA-beta, insulinogenic index, HOMA-IR,
      Matsuda index and HbA1c, disposition index was an independent risk factor for
      impaired GF [odds ratio (95% confidence interval): 2.87 (1.70-4.83), P<0.001].
      CONCLUSION: Pancreatic beta cell dysfunction is associated with GF and causes
      endothelial injury in CAD patients.

PMID- 28743061
TI  - Circulating CTRP9 levels are increased in patients with newly diagnosed type 2
      diabetes and correlated with insulin resistance.
AB  - AIMS: C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has been shown
      to promote lipid metabolism, enhance insulin sensitivity and protect against
      cardiovascular disease. However, previous studies in humans have produced
      controversial results regarding the association between CTRP9 and insulin
      resistance. The objective of this study was to evaluate the relationships between
      CTRP9 and insulin resistance in Chinese population. METHODS: Subjects with normal
      glucose tolerance (NGT, n=108), impaired glucose tolerance (IGT, n=92), and newly
      diagnosed type 2 diabetes mellitus (nT2DM, n=106) were recruited to determining
      the circulating CTRP9 and adiponectin levels by enzyme linked immunosorbent
      assay. Anthropometric and biochemical measurements related to insulin resistance,
      adiposity and lipid profile were examined for all participants. Oral glucose
      tolerance test was performed in healthy subjects (17 male and 17 female).
      RESULTS: Circulating CTRP9 level was significantly higher in both IGT and nT2DM
      than in individuals with NGT. Overweight/obese subjects had much higher CTRP9
      levels than lean individuals, and in all subjects, females also had higher CTRP9
      levels than males. In addition, circulating CTRP9 level was positively correlated
      with markers of obesity and insulin resistance, including body mass index,
      fasting blood glucose, insulin, HbA1c, homeostasis model assessment of insulin
      resistance and low-density lipoprotein-cholesterol, while was inversely
      correlated with high-density lipoprotein-cholesterol and adiponectin. Moreover,
      hyperglycemia during an oral glucose challenge increased circulating CTRP9
      concentrations. CONCLUSIONS: We conclude that CTRP9 was strongly associated with
      insulin resistance, suggesting that CTRP9 might be important in the development
      of type 2 diabetes.

PMID- 28743062
TI  - Peripheral leucocytes and tissue gene expression of granzyme B/perforin system
      and serpinB9: Impact on inflammation and insulin resistance in coronary
      atherosclerosis.
AB  - AIM: The imbalance between proapoptotic granzyme B (GZB)/perforin (PRF) system
      and proteinase inhibitor-9 (PI-9; serpinB9); the only known inhibitor of human
      GZB, has been demonstrated in atherosclerosis. However, their role in
      atherosclerosis with the impact of type 2 diabetes mellitus (DM) as well as their
      contribution to hallmarks of atherosclerosis is not clear. SUBJECTS AND METHODS:
      ELISA for serum insulin, high sensitivity C-reactive protein (hsCRP) and GZB
      levels in atherosclerotic coronary artery diseases (CAD) patients were estimated
      in comparison to apparently healthy controls, while GZB, PRF and PI-9 mRNA
      expression levels were quantified by Taqman RT-PCR in both peripheral leucocytes
      and atherosclerotic tissues. RESULTS: Atherosclerotic patients showed
      significantly higher insulin, hsCRP and GZB levels than controls. There was a
      significant increase in GZB mRNA expression and significant reduction in PI-9
      mRNA in both patient peripheral leucocytes and atherosclerotic lesions, while PRF
      mRNA increased significantly only in atherosclerotic tissues. PI-9 mRNA levels
      were significantly lower in patients with diabetes than patients without
      diabetes. In contrast to positive modulating effect of GZB, regression analysis
      revealed negative modulating effect of PI-9 on inflammation and insulin
      resistance. Circulating PI-9 mRNA was inversely contributed to CAD severity.
      CONCLUSIONS: GZB and PI-9 could be effective modulators for inflammation and
      insulin resistance in atherosclerosis.

PMID- 28743063
TI  - Glutamate pathways of the beta-cell and the control of insulin secretion.
AB  - Pancreatic beta-cells secrete insulin in response to circulating glucose, thereby
      maintaining euglycemia. Inside the beta-cell, glucose is transformed into
      intracellular signals stimulating exocytosis. While calcium is an obligatory
      messenger, this ion is not sufficient to promote the full secretory response.
      Accordingly, glucose metabolism produces the additive factor glutamate that
      participates to an amplifying pathway of the calcium signal. Although
      intracellular glutamate potentiates insulin secretion, extracellular glutamate
      may activate ionotropic receptors. As a consequence of such activation, insulin
      exocytosis is slowed down. Therefore, for the beta-cell glutamate is a double
      edged sword, an amplifying pathway and a negative feedback, illustrating the
      principle of homeostasis.

PMID- 28743064
TI  - Health status and mobility limitations are associated with residential and
      employment status in schizophrenia and bipolar disorder.
AB  - INTRODUCTION: Schizophrenia (SCZ) and bipolar disorder (BP) are linked to
      multiple impairments in everyday functioning which share cognitive and symptom
      risk factors. Other risk factors for critical aspects of every day functioning
      (e.g., gainful employment; residential independence) such as physical health have
      not been evaluated, despite poor health in SCZ and BP. METHODS: We analyzed 20
      year follow-up data from the Suffolk County Mental Health Project cohort of
      consecutive first admissions with a psychotic disorder to 12 psychiatric
      facilities in Suffolk County, NY, between September 1989 and December 1995. Both
      20-year symptom, health, and cognition data, and the 20-year course of weight
      gain were included as predictors of employment and residence status. RESULTS: The
      analysis sample consisted of 122 participants with SCZ ad BP, with SCZ
      participants less likely to work or live independently. Correlational analyses
      showed symptoms and cognition predicted vocational outcomes in both samples. The
      effect of diagnosis was significant for both gainful employment and independence
      in residence. After consideration of diagnosis, mobility and negative symptoms
      predicted gainful employment in both samples, but there were no additional
      predictors of residential independence. Prospective analysis of BMI found that
      baseline BMI, but not changes during the 20-year follow up, predicted labor force
      participation. DISCUSSION: Health status limitations were associated with
      residential and, particularly, employment status independent from other,
      previously established predictors of everyday outcomes, including cognition and
      symptoms. The importance of health status limitations for predicting outcome was
      confirmed in both SCZ and BP, with schizophrenia representing the more impaired
      group.

PMID- 28743065
TI  - Enantiomerization and stereoselectivity in bioaccumulation of furalaxyl in
      Tenebrio molitor larvae.
AB  - Furalaxyl is a chiral pesticide and widely used in modern agriculture as racemate
      mixture. The enantiomerization and enantioselecive bioaccumulation by a single
      dose of furalaxyl to Tenebrio molitor larvae under laboratory conditions were
      studied using a high-performance liquid chromatography tandem mass spectroscopy
      method based on a ChiralPAK IC column. Our results showed that a significant
      enantiomerization (interconversion between R-enantiomer and S-enantiomer) was
      observed in Tenebrio molitor larvae under R- or S-furalaxyl exposure. Though the
      two furalaxyl enantiomers exhibited low-capacity of bioaccumulation in Tenebrio
      molitor larvae, bioaccumulation of rac-furalaxyl was enantioselective with a
      preferential accumulation of S-furalaxyl at 10mg/kg dosage exposure. In addition,
      enantiomerization and enantioselective degradation of the two enantiomers was not
      observed in wheat bran. These results showed that enantioselectivtiy of furalaxyl
      enantiomers was an important process combined with degradation, metabolism and
      enatiomerization in organisms.

PMID- 28743066
TI  - Toxic effects of juvenile sablefish, Anoplopoma fimbria by ammonia exposure at
      different water temperature.
AB  - Juvenile sablefish, Anoplopoma fimbria (mean length 17.1+/-2.4cm, and mean weight
      75.6+/-5.7g) were used to evaluate toxic effects on antioxidant systems, immune
      responses, and stress indicators by ammonia exposure (0, 0.25, 0.75, and
      1.25mg/L) at different water temperature (12 and 17 degrees C) in 1 and 2 months.
      In antioxidant responses, superoxide dismutase (SOD) and catalase (CAT) were
      significantly increased by ammonia exposure, whereas glutathione (GSH) was
      decreased. In immune responses, lysozyme and phagocytosis activity were
      significantly increased by ammonia exposure. In stress indicators, plasma
      glucose, heat shock protein 70 (HSP 70), and cortisol were significantly
      increased. At high water temperature (17 degrees C), alterations by ammonia
      exposure were more distinctly. The results of this study indicated that ammonia
      exposure can induce toxic effects in the sablefish, and high water temperature
      can affect the ammonia exposure toxicity.

PMID- 28743067
TI  - "We must cooperate with one another against the Enemy": Agency and activism in
      school-aged children as protective factors against ongoing war trauma and
      political violence in the Gaza Strip.
AB  - This exploratory qualitative study investigated self-perceived risk and
      protection factors that may reinforce the ability of children living in refugee
      camps on the Gaza Strip to adjust to a traumatic and risky life context
      characterized by loss and dispossession. The sample comprised 200 Palestinian
      children recruited at primary schools in four refugee camps in the Gaza Strip
      following the Israeli military operation "Pillar of Defence" in 2012. Thematic
      content analysis was applied to written materials and narratives produced by the
      children. Environment, friends, emotions, family, play, self, sociality, health,
      school, and spirituality were the dimensions that emerged from the narrative
      texts. Palestinian children's psychological adaptability and ability to
      reposition themselves along the continuum between ease and disease is underpinned
      by constant political agency and activism - a dimension that guides sense-making
      activities in a traumatizing environment marked by continuous uncertainty, loss
      and bereavement. We therefore recommend a politically-informed focus, both when
      assessing children and when designing intervention for them in contexts of
      chronic political violence and war.

PMID- 28743068
TI  - Applying Monte-Carlo simulations to optimize an inelastic neutron scattering
      system for soil carbon analysis.
AB  - Computer Monte-Carlo (MC) simulations (Geant4) of neutron propagation and
      acquisition of gamma response from soil samples was applied to evaluate INS
      system performance characteristic [minimal detectible level (MDL), sensitivity]
      for soil carbon measurement. The INS system model with best performance
      characteristics was determined based on MC simulation results. Measurements of
      MDL using an experimental prototype based on this model demonstrated good
      agreement with simulated data. This prototype will be used as the base
      engineering design for a new INS system.

PMID- 28743069
TI  - The influence of 134Cs on the 137Cs gamma-spectrometric peak-to-valley ratio and
      improvement of the peak-to-valley method by limiting the detector field of view.
AB  - The peak-to-valley method was investigated under laboratory conditions and in
      situ with respect to both 134Cs perturbation of the 137Cs valley and use of
      collimation. The 134Cs perturbation is significant down to 134Cs:137Cs activity
      ratios of 1:100. In these cases the full energy peaks from 134Cs (796 and 802keV)
      and associated valley should be used instead of the peak and valley from the
      137Cs 662keV peak. Use of collimators in situ outside Fukushima Daiichi
      significantly increased PTV for 134Cs.

PMID- 28743070
TI  - Tracking binding modes of 1,2,4-trisubstituted imidazolinone P38 MAP kinase and
      ERK-2 inhibitors.
AB  - Putative binding modes of recently reported p38 MAP Kinase and ERK-2 inhibitors
      containing 1,2,4-tri-substituted imidazolinone have been investigated using
      molecular docking methods In the case of p38 MAP Kinase, X-ray structures with
      both DFG-in and DFG-out conformations of the activation loop have been employed
      for docking studies. The present investigations demonstrate that the DFG-out
      conformation of the activation loop in p38 MAP Kinase accommodates the 1,2,4-tri
      substituted imidazolinones with greater computed binding affinities than the
      alternative DFG-in conformation. The best scoring binding modes in ERK-2 are
      distinctly different from those found in the p38 MAP Kinase structures. Both sets
      of binding modes are characterized by an extensive network of hydrophobic and pi
      cation interactions, with the hinge region showing little hydrogen bonding
      propensity with the top-ranked poses. Thus, these docking studies provide a
      putative pathway for lead optimizations in which hydrogen bonding interactions
      with the hinge region residues are feasible.

PMID- 28743071
TI  - Prediction of protein structural class for low-similarity sequences using Chou's
      pseudo amino acid composition and wavelet denoising.
AB  - Prediction of protein structural class plays an important role in protein
      structure and function analysis, drug design and many other biological
      applications. Prediction of protein structural class for low-similarity sequences
      is still a challenging task. Based on the theory of wavelet denoising, this paper
      presents a novel method of prediction of protein structural class for the first
      time. Firstly, the features of the protein sequence are extracted by using Chou's
      pseudo amino acid composition (PseAAC). Then the extracted feature information is
      denoised by two-dimensional (2D) wavelet. Finally, the optimal feature vectors
      are input to support vector machine (SVM) classifier to predict protein
      structural classes. We obtained significant predictive results using jackknife
      test on three low-similarity protein structural class datasets 25PDB, 1189 and
      640, and compared our method with previous methods The results indicate that the
      method proposed in this paper can effectively improve the prediction accuracy of
      protein structural class, which will be a reliable tool for prediction of protein
      structural class, especially for low-similarity sequences.

PMID- 28743072
TI  - Molecular modeling and molecular dynamics simulation study of archaeal leucyl
      tRNA synthetase in complex with different mischarged tRNA in editing
      conformation.
AB  - Aminoacyl-tRNA synthetases (aaRSs) play important roles in maintaining the
      accuracy of protein synthesis. Some aaRSs accomplish this via editing mechanisms,
      among which leucyl-tRNA synthetase (LeuRS) edits non-cognate amino acid norvaline
      mainly by post-transfer editing. However, the molecular basis for this pathway
      for eukaryotic and archaeal LeuRS remain unclear. In this study, a complex of
      archaeal P. horikoshii LeuRS (PhLeuRS) with misacylated tRNALeu was modeled
      wherever tRNA's acceptor stem was oriented directly into the editing site. To
      understand the distinctive features of organization we reconstructed a complex of
      PhLeuRS with tRNA and visualize post-transfer editing interactions mode by
      performing molecular dynamics (MD) simulation studies. To study molecular basis
      for substrate selectivity by PhLeuRS's editing site we utilized MD simulation of
      the entire LeuRS complexes using a diverse charged form of tRNAs, namely norvalyl
      tRNALeu and isoleucyl-tRNALeu. In general, the editing site organization of LeuRS
      from P.horikoshii has much in common with bacterial LeuRS. The MD simulation
      results revealed that the post-transfer editing substrate norvalyl-A76, binds
      more strongly than isoleucyl-A76. Moreover, the branched side chain of isoleucine
      prevents water molecules from being closer and hence the hydrolysis reaction
      slows significantly. To investigate a possible mechanism of the post-transfer
      editing reaction, by PhLeuRS we have determined that two water molecules (the
      attacking and assisting water molecules) are localized near the carbonyl group of
      the amino acid to be cleaved off. These water molecules approach the substrate
      from the opposite side to that observed for Thermus thermophilus LeuRS (TtLeuRS).
      Based on the results obtained, it was suggested that the post-transfer editing
      mechanism of PhLeuRS differs from that of prokaryotic TtLeuRS.

PMID- 28743073
TI  - In-situ biodegradation potential of 1,2-DCA and VC at sites with different
      hydrogeological settings.
AB  - This paper investigates the feasibility of applying in-situ Bioremediation (ISB)
      to three sites contaminated with vinyl chloride and/or chlorinated alkanes such
      as 1,2-DCA and 1,1,2-TCA, presenting distinct hydrogeological settings and
      history of contaminant loading. Biotransformation of these compounds is well
      established in laboratory studies and pure cultures. Due to confidential aspects,
      however, few field data are available to support real case studies to the
      predictability of their fate and lifetime in soil and groundwater. Bio-Trap(r) In
      Situ Microcosm (ISM) studies were performed in selected monitoring wells, and
      consisted of a control unit which simulated Monitored Natural Attenuation
      conditions and other units which were amended with either lactate, emulsified
      vegetable oil (EVO) or molasses as electron donors. For wells with moderate Dhc
      counts, the ISM study demonstrated that electron donor addition could stimulate
      further growth of Dhc and enhance reductive dechlorination. Conversely, for wells
      with high population counts, substrate addition did not alter results
      significantly. Site-specific determining factors that most influenced the
      biodegradation results were microbial activity, soil texture and presence of
      organic matter, site pH, redox conditions and presence of free phase.

PMID- 28743074
TI  - Coronary perfusion pressure and compression quality in maternal cardiopulmonary
      resuscitation in supine and left-lateral tilt positions: A prospective, crossover
      study using mannequins and swine models.
AB  - OBJECTIVE: The risk of maternal and fetal mortality is high if cardiopulmonary
      arrest occurs during pregnancy. To assess the best position for maternal
      cardiopulmonary resuscitation (CPR), a prospective randomized crossover study was
      undertaken, involving basic life support mannequin-based simulation (BLS-MS) and
      a swine model of pulseless electrical activity (an unstable cardiac state)
      incorporating a fetal mannequin (PEA-FM). STUDY DESIGN: The BLS-MS (performed by
      certified rescuers) served to evaluate the quality of chest compressions in 30
      degrees  left lateral tilt (LLT) and supine positions. Based on a 5-point scale,
      each rescuer subjectively graded their experience. The PEA-FM model was used to
      compare coronary perfusion pressure readings during CPR in supine, supine with
      left uterine displacement, 30 degrees  LLT, and 30 degrees  right lateral tilt
      positions. Compression rate and correctness of hand position, compression depth,
      and recoil were measures of compression quality (BLS-MS). RESULTS: Compared with
      LLT position, supine position enabled correct hand position (rate: 0.99 vs 0.88;
      p<0.05) and compression depth (rate: 0.76 vs 0.36; p<0.001) significantly more
      often. Moreover, BLS-MS rescuers found chest compressions significantly easier to
      perform with the mannequin in supine (vs LLT) position (difficulty score: 1.75 vs
      3.95; p<0.001). In the PEA-FM study arm, supine position with left uterine
      displacement and right lateral tilt positions had the highest and lowest recorded
      coronary perfusion pressure readings, respectively. CONCLUSION: Supine position
      with left uterine displacement is optimal for maternal CPR.

PMID- 28743075
TI  - Preference of Arabidopsis thaliana GH3.5 acyl amido synthetase for growth versus
      defense hormone acyl substrates is dictated by concentration of amino acid
      substrate aspartate.
AB  - The GH3 family of adenylating enzymes conjugate acyl substrates such as the
      growth hormone indole-3-acetic acid (IAA) to amino acids via a two-step reaction
      of acyl substrate adenylation followed by amino acid conjugation. Arabidopsis
      thaliana GH3.5 was previously shown to be unusual in that it could adenylate both
      IAA and the defense hormone salicylic acid (SA, 2-hydroxybenzoate). Our detailed
      studies of the kinetics of GH3.5 on a variety of auxin and benzoate substrates
      provides insight into the acyl preference and reaction mechanism of GH3.5. For
      example, we found GH3.5 activity on substituted benzoates is not defined by the
      substitution position as it is for GH3.12/PBS3. Most importantly, we show that
      GH3.5 strongly prefers Asp as the amino acid conjugate and that the concentration
      of Asp dictates the functional activity of GH3.5 on IAA vs. SA. Not only is Asp
      used in amino acid biosynthesis, but it also plays an important role in nitrogen
      mobilization and in the production of downstream metabolites, including pipecolic
      acid which propagates defense systemically. During active growth, [IAA] and [Asp]
      are high and the catalytic efficiency (kcat/Km) of GH3.5 for IAA is 360-fold
      higher than with SA. GH3.5 is expressed under these conditions and conversion of
      IAA to inactive IAA-Asp would provide fine spatial and temporal control over
      local auxin developmental responses. By contrast, [SA] is dramatically elevated
      in response to (hemi)-biotrophic pathogens which also induce GH3.5 expression.
      Under these conditions, [Asp] is low and GH3.5 has equal affinity (Km) for SA and
      IAA with similar catalytic efficiencies. However, the concentration of IAA tends
      to be very low, well below the Km for IAA. Therefore, GH3.5 catalyzed formation
      of SA-Asp would occur, fine-tuning localized defensive responses through
      conversion of active free SA to SA-Asp. Taken together, we show how GH3.5, with
      dual activity on IAA and SA, can integrate cellular metabolic status via Asp to
      provide fine control of growth vs. defense outcomes and hormone homeostasis.

PMID- 28743076
TI  - LC-MS/MS-ESI method for simultaneous quantification of darolutamide and its
      active metabolite, ORM-15341 in mice plasma and its application to a
      pharmacokinetic study.
AB  - A sensitive and rapid LC-MS/MS method was developed and validated for the
      simultaneous quantitation of darolutamide and its active metabolite i.e. ORM
      15341 in 50MUL mice plasma using bicalutamide as an internal standard (I.S.) as
      per regulatory guidelines. Sample processing was accomplished through liquid
      liquid extraction. Chromatographic separation was achieved using an Atlantis C18
      column with an isocratic mobile phase comprising 0.2% formic acid:acetonitrile
      (35:65, v/v) at a flow rate of 0.8mL/min within 2.5min. Detection and
      quantitation were done by multiple reaction monitoring on a triple quadrupole
      mass spectrometer following the transitions: m/z 397->202, 395->202 and 429->255
      for darolutamide, ORM-15341 and I.S, respectively in the negative ionization
      mode. The calibration curve was linear from 0.61-1097ng/mL for both darolutamide
      and ORM-15341. The intra- and inter-day precisions were in the range of 1.34-13.8
      and 4.85-12.9 and 3.91-13.7 and 6.54-14.2%, for darolutamide and ORM-15341,
      respectively. Darolutamide and ORM-15341 were found to be stable under different
      stability conditions. The validated method was applied to a pharmacokinetic study
      in mice.

PMID- 28743077
TI  - Characterization and quantitative analysis of phenolic derivatives in
      Longxuetongluo Capsule by HPLC-DAD-IT-TOF-MS.
AB  - Longxuetongluo Capsule (LTC), which is derived from the total phenolic extract of
      Chinese dragon's blood, has been proved to be safe as well as effective towards
      ischemic stroke. However, the effective material basis remains unclear. The
      present study thereby focused on the clarification of the qualitative and
      quantitative properties for the phenolic derivatives in LTC. Regarding homolog
      focused chemical profiling, the mass fragmentation patterns of the primary
      subtypes of phenolic compounds such as homoisoflavanones, flavanes, chalcones,
      and flavonoid oligomers were summarized by assaying authentic references with
      hybrid ion trap time-of-flight mass spectrometry, and the chemical structures of
      124 phenolic compounds, in total, were unambiguously or tentatively annotated in
      LTC by matching the accurate mass spectral profiles with the proposed mass
      cracking rules and those reference substances. Afterwards, simultaneous
      determination of 12 primary phenolic compounds was carried out in different
      batches of LTC using HPLC-DAD, after that the method was proved to be accurate,
      precise, and reproducible according to diverse method validation assays. The
      obtained findings are expected to be meaningful for clarifying the effective
      substances and quality assessment of LTC.

PMID- 28743078
TI  - Metabolite identification of AZD8055 in Sprague-Dawley rats after a single oral
      administration using ultra-performance liquid chromatography and mass
      spectrometry.
AB  - AZD8055 is an ATP-competitive specific dual mTOR inhibitor and exhibited potent
      antitumor activity on several types of solid tumors. However, the metabolism of
      AZD8055 in the body still remains unknown. In this study, metabolite
      identification of AZD8055 was performed using ultra high-performance liquid
      chromatography-ion trap mass spectrometry (UHPLC-IT-MS) through both in vitro and
      in vivo approaches using rat liver microsomes (RLMs) and rat plasma, urine and
      feces, respectively. A total of eight putative metabolites (five phase I and
      three phase II) were identified, and a tentative metabolic pathway was suggested
      for the first time. Considering the accurate mass and mass fragmentations of the
      detected metabolites, their plausible structures were suggested. Demethylation,
      hydroxylation, oxidation and morpholine ring opening were the major
      biotransformation processes for the phase-I metabolism, while phase-II
      metabolites were merely generated by the glucuronide conjugation reaction. The
      cumulative excretion of AZD8055 in urine and feces was 0.13% and 1.11% of the
      dose, respectively. When the semi-quantitative analysis of the metabolites was
      performed using UHPLC-MS/MS (ultra-performance liquid chromatography tandem mass
      spectrometry) to evaluate the overall trend of metabolites formation and
      excretion, AZD8055 was excreted more in the form of the metabolites than itself
      and their formation was very fast. Therefore it was presumed that
      biotransformation was playing a crucial role in its elimination. Ultimately, this
      study provides novel insights regarding the in vitro and in vivo
      biotransformations of AZD8055. Further investigations of metabolites of this
      potent anti-cancer compound could be beneficial for the antitumor drug design and
      development process.

PMID- 28743079
TI  - Impact of lyophilized Lactobacillus salivarius DSPV 001P administration on growth
      performance, microbial translocation, and gastrointestinal microbiota of broilers
      reared under low ambient temperature.
AB  - This study was undertaken with the aim of investigating the effects of dietary
      supplementation of probiotic strain Lactobacillus salivarius DSPV 001P on growth
      performance, microbial translocation, and gastrointestinal microbiota of broilers
      reared under low ambient temperature. Two hundred and forty, one-day-old male
      Cobb broilers were randomly distributed into two treatment groups, a probiotic
      group and a control group, with four replicates per treatment and 30 broilers per
      replicate. The temperature of the broiler house was maintained at 18-22 degrees C
      during the first three weeks, after which the temperature was at range of 8
      degrees C to 12 degrees C. The results showed that probiotic treatment
      significantly improved body weight of broilers when compared with the control
      group. After 42days, the weight means were 2905+/-365.4g and 2724+/-427.0g,
      respectively. Although there were no significant differences, dietary inclusion
      of L. salivarius tended to increase feed intake and to reduce feed conversion
      ratio during the six-week experimental period. Similarly, supplementation tended
      to reduce the rate of mortality, with 12 deaths occurring in the probiotic group,
      and 20 in the control group. However, no differences were observed in intestinal
      bacterial concentrations of Enterobacteriaceae, E.coli, and lactic acid bacteria
      in both crop and caecum among treatments. Through our study, it appears that L.
      salivarius DSPV 001P was non-pathogenic, safe and beneficial to broilers, which
      implies that it could be a promising feed additive, thus enhancing the growth
      performance of broilers and improving their health.

PMID- 28743080
TI  - The role of hexon in egg drop syndrome virus (EDSV) inducing apoptosis in duck
      embryo fibroblast cells.
AB  - Although extensive efforts have been made to understand adenovirus infection in
      human cells, little is known for egg drop syndrome virus (EDSV) infection in the
      avian-derived cells. In this study, the effects of EDSV infection as well as the
      possible role hexon protein, the main building block of the EDSV capsid, on
      apoptosis induction in duck embryo fibroblast (DEF) cells was examined. Flow
      cytometry analysis and TUNEL assay revealed that EDSV infection induced
      significant apoptosis in DEF cells compared with mock infected cells.
      Interestingly, the increase of the apoptosis rate detected in EDSV infected DEF
      cells were accompanied by an increased virus load in cells in a time-dependent
      manner. Furthermore, a time-dependent decrease in hexon protein expression levels
      in hexon transfected DEF cells in parallel with a gradual decrease in TUNEL
      labeling cells was also observed in the current study. In addition, caspase
      activity detection and western blot analysis indicates that either EDSV infection
      or EDSV hexon transfection both induced apoptosis of DEF cells via activating
      both the exogenous and the mitochondrial pathway.

PMID- 28743081
TI  - Mycobacterium tuberculosis PPE44 (Rv2770c) is involved in response to multiple
      stresses and promotes the macrophage expression of IL-12 p40 and IL-6 via the
      p38, ERK, and NF-kappaB signaling axis.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a formidable
      threat to global public health. The successful intracellular persistence of M.
      tuberculosis significantly contributes to the intractability of tuberculosis.
      Proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) are
      mycobacterial exclusive protein families that widely reported to be involved in
      the bacterial virulence, physiology and interaction with host. Rv2770c (PPE44), a
      predicted virulence factor, was up-regulated upon the infected guinea pig lungs.
      To investigate the role of Rv2770c, we heterologously expressed the PPE44 in the
      nonpathogenic fast-growing M. smegmatis strain. Subcellular location analysis
      demonstrated that Rv2770c is a cell wall associated protein, suggestive of a
      potential candidate involved in host-pathogen interaction. The Rv2770c can
      enhance M. smegmatis survival within macrophages and under stresses such as H2O2,
      SDS, diamide exposure, and low pH condition. M. smegmatis expressing Rv2770c is
      more virulent as testified by the increased death of macrophages and the
      increased expression of interlukin-6 (IL-6) and interlukin-12p40 (IL-12p40).
      Moreover, Rv2770c altered the secretion of IL-6 and IL-12p40 of macrophages via
      NF-kappaB, ERK1/2 and p38 MAPK axis. Taken together, this study implicated that
      Rv2770c was a virulent factor actively engaged in the interaction with host
      macrophage.

PMID- 28743082
TI  - Characterization and evaluation of nanoencapsulated diethylcarbamazine in model
      of acute hepatic inflammation.
AB  - Previous studies from our laboratory have demonstrated that Diethylcarbamazine
      (DEC) is a potent anti-inflammatory drug. The aim of the present study was to
      characterize the nanoencapsulation of DEC and to evaluate its effectiveness in a
      model of inflammation for the first time. C57BL/6 mice were divided into six
      groups: 1) Control; 2) Carbon tetrachloride (CCl4); 3) DEC 25mg/kg+CCl4; 4) DEC
      50mg/kg+CCl4; 5) DEC-NANO 05mg/kg+CCl4 and 6) DEC-NANO 12.5mg/kg+CCl4. Liver
      fragments were stained with hematoxylin-eosin, and processed for Western blot,
      ELISA and immunohistochemistry. Serum was also collected for biochemical
      measurements. Carbon tetrachloride induced hepatic injury, observed through
      increased inflammatory markers (TNF-alpha, IL-1beta, PGE2, COX-2 and iNOS),
      changes in liver morphology, and increased serum levels of total cholesterol,
      triglycerides, TGO and TGP, LDL, as well as reduced HDL levels. Nanoparticles
      containing DEC were characterized by diameter, polydispersity index and zeta
      potential. Treatment with 12.5 nanoencapsulated DEC exhibited a superior anti
      inflammatory action to the DEC traditional dose (50mg/kg) used in murine assays,
      restoring liver morphology, improving serological parameters and reducing the
      expression of inflammatory markers. The present formulation of nanoencapsulated
      DEC is therefore a potential therapeutic tool for the treatment of inflammatory
      hepatic disorders, permitting the use of smaller doses and reducing treatment
      time, while maintaining high efficacy.

PMID- 28743083
TI  - Hall effect biosensors with ultraclean graphene film for improved sensitivity of
      label-free DNA detection.
AB  - The quality of graphene strongly affects the performance of graphene-based
      biosensors which are highly demanded for the sensitive and selective detection of
      biomolecules, such as DNA. This work reported a novel transfer process for
      preparing a residue-free graphene film using a thin gold supporting layer. A Hall
      effect device made of this gold-transferred graphene was demonstrated to
      significantly enhance the sensitivity (~ 5 times) for hybridization detection,
      with a linear detection range of 1pM to 100nM for DNA target. Our findings
      provide an efficient method to boost the sensitivity of graphene-based biosensors
      for DNA recognition.

PMID- 28743084
TI  - Graphene oxide@gold nanorods-based multiple-assisted electrochemiluminescence
      signal amplification strategy for sensitive detection of prostate specific
      antigen.
AB  - A novel and competitive electrochemiluminescence (ECL) aptasensor for prostate
      specific antigen (PSA) assay was constructed using gold nanorods functionalized
      graphene oxide (GO@AuNRs) multilabeled with glucose oxidase (GOD) and
      streptavidin (SA) toward luminol-based ECL system. A strong initial ECL signal
      was achieved by electrodeposited gold (DpAu) on the electrode because of gold
      nanoparticles (AuNPs) motivating the luminol ECL signal. The signal probes
      prepared by loading GOD and SA-biotin-DNA on GO@AuNRs were used for achieving
      multiple signal amplification. In the absence of PSA, the signal probes can be
      attached on the electrode by hybridization reaction between PSA aptamer and
      biotin-DNA. In this state, the GOD loaded on the probe could catalyze glucose to
      in situ produce H2O2 and then AuNRs catalyze H2O2 to generate abundant reactive
      oxygen species (ROSs) in luminol ECL reaction. Both the high-content GOD and
      AuNRs in the signal probe amplified the ECL signal in the ECL system. Moreover,
      the combination of SA with biotin-DNA further expands ECL intensity. The
      integration of such amplifying effects in this protocol endows the aptasensor
      with high sensitivity and good selectivity for PSA detection. This aptasensor
      exhibits a linear relation in the range of 0.5pgmL-1 to 5.0ngmL-1 with the
      detection limit of 0.17pgmL-1 (S/N = 3). Besides, the strategy was successfully
      applied in determination of human serum samples with recovery of 81.4-116.0%.

PMID- 28743085
TI  - Direct electrodeposition of Graphene enhanced conductive polymer on
      microelectrode for biosensing application.
AB  - Engineering of neural interface with nanomaterials for high spatial resolution
      neural recording and stimulation is still hindered by materials properties and
      modification methods. Recently, poly(3,4-ethylene-dioxythiophene) (PEDOT) has
      been widely used as an electrode-tissue interface material for its good
      electrochemical property. However, cracks and delamination of PEDOT film under
      pulse stimulation are found which restrict its long-term applications. This paper
      develops a flexible electrochemical method about the co-deposition of graphene
      with PEDOT on microelectrode sites to enhance the long-term stability and improve
      the electrochemical properties of microelectrode. This method is unique and
      profound because it co-deposits graphene with PEDOT on microelectrode sites
      directly and avoids the harmful post reduction process. And, most importantly,
      significantly improved electrochemical performances of the modified
      microelectrodes (compared to PEDOT-GO) are demonstrated due to the large
      effective surface area, good conductivity and excellent mechanical property of
      graphene. Furthermore, the good mechanical stability of the composites is
      verified by ultrasonication and CV scanning tests. In-vivo acute implantation of
      the microelectrodes reveals the modified microelectrodes show higher recording
      performance than the unmodified ones. These findings suggest the composites are
      excellent candidates for the applications of neural interface.

PMID- 28743086
TI  - Effect of cinnamon (Cinnamomum verum) bark essential oil on the halitosis
      associated bacterium Solobacterium moorei and in vitro cytotoxicity.
AB  - OBJECTIVES: Halitosis, also known as bad breath or oral malodour, is a condition
      affecting a large proportion of the population. Solobacterium moorei is a Gram
      positive anaerobic bacterium that has been specifically associated with
      halitosis. In this study, we investigated the effects of essential oils, more
      particularly cinnamon bark oil, on growth, biofilm formation, eradication and
      killing, as well as hydrogen sulfide (H2S) production by S. moorei. METHODS: A
      broth microdilution assay was used to determine the antibacterial activity of
      essential oils. Biofilm formation was assessed by a crystal violet staining assay
      and scanning electron microscopy. The biofilm of S. moorei was characterized by
      enzymatic treatments. Biofilm killing was determined by a luminescence assay
      monitoring ATP production. H2S production was quantified with a colorimetric
      assay. The biocompatibility of cinnamon oil was investigated using a gingival
      keratinocyte cell line. RESULTS: Among the ten essential oils tested, cinnamon
      oil was found to be the most powerful against S. moorei with MIC and MBC values
      of 0.039% and 0.156%, respectively. The biofilm formed by S. moorei was then
      characterized. The fact that DNase I and to a lesser extent proteinase K
      significantly reduced biofilm formation by S. moorei and induced its eradication
      suggests that the extracellular matrix of S. moorei biofilm may be mainly
      containing a DNA backbone associated with proteins. At concentrations below the
      MIC, cinnamon oil reduced S. moorei biofilm formation that resulted from an
      attenuation of bacterial growth. It was also found that treatment of a pre-formed
      biofilm of S. moorei with cinnamon oil significantly decreased its viability
      although it did not cause its eradication. Cinnamon oil had an inhibitory effect
      on the production of H2S by S. moorei. Lastly, it was found that at
      concentrations effective against S. moorei, no significant loss of viability in
      gingival keratinocytes occurred after a 1-h exposure. CONCLUSIONS: Our study
      brought evidence that cinnamon oil may be a promising substance to incorporate
      into oral hygiene products for controlling bad breath by inhibiting growth,
      killing biofilm, and reducing H2S production by S. moorei. Moreover, at the
      effective concentrations, cinnamon oil was found to have no toxic effects on oral
      keratinocytes.

PMID- 28743087
TI  - Quinoline containing acetyl hydrazone: An easily accessible switch-on optical
      chemosensor for Zn2.
AB  - A simple chemosensor, namely, N-((quinolin-8-yl)methylene)acetohydrazide (1) was
      synthesized and used as an off-on fluorescence sensor, which exhibits high
      selectivity toward Zn2+ in aqueous media. The probe has large Stokes shift of
      >200nm, and its detection limit for Zn2+ is 89.3nM. The binding process was
      confirmed through UV-vis absorption analysis, fluorescence measurements, mass
      spectroscopy study, 1H NMR spectra and density functional theory calculation. The
      crystal structures of Zn2+, Ni2+, and Cu2+ complexes based on 1 were determined
      through X-ray crystallographic analysis. The fluorescent probe was then applied
      to monitor intracellular Zn2+ in HeLa cells.

PMID- 28743088
TI  - Chitosan derived co-spheroids of neural stem cells and mesenchymal stem cells for
      neural regeneration.
AB  - Chitosan has been considered as candidate biomaterials for neural applications.
      The effective treatment of neurodegeneration or injury to the central nervous
      system (CNS) is still in lack nowadays. Adult neural stem cells (NSCs) represents
      a promising cell source to treat the CNS diseases but they are limited in number.
      Here, we developed the core-shell spheroids of NSCs (shell) and mesenchymal stem
      cells (MSCs, core) by co-culturing cells on the chitosan surface. The NSCs in
      chitosan derived co-spheroids displayed a higher survival rate than those in NSC
      homo-spheroids. The direct interaction of NSCs with MSCs in the co-spheroids
      increased the Notch activity and differentiation tendency of NSCs. Meanwhile, the
      differentiation potential of MSCs in chitosan derived co-spheroids was
      significantly enhanced toward neural lineages. Furthermore, NSC homo-spheroids
      and NSC/MSC co-spheroids derived on chitosan were evaluated for their in vivo
      efficacy by the embryonic and adult zebrafish brain injury models. The locomotion
      activity of zebrafish receiving chitosan derived NSC homo-spheroids or NSC/MSC co
      spheroids was partially rescued in both models. Meanwhile, the higher survival
      rate was observed in the group of adult zebrafish implanted with chitosan derived
      NSC/MSC co-spheroids as compared to NSC homo-spheroids. These evidences indicate
      that chitosan may provide an extracellular matrix-like environment to drive the
      interaction and the morphological assembly between NSCs and MSCs and promote
      their neural differentiation capacities, which can be used for neural
      regeneration.

PMID- 28743089
TI  - Understanding the interaction of concanavalin a with mannosyl glycoliposomes: A
      surface plasmon resonance and fluorescence study.
AB  - The specificity of carbohydrate-protein interaction is a key factor in many
      biological processes and it is the foundation of technologies using
      glycoliposomes in drug delivery. The incorporation of glycolipids in vesicles is
      expected to increase their specificity toward particular targets such as lectins;
      however, the degree of exposure of the carbohydrate moiety at the liposome
      surface is a crucial parameter to be considered in the interaction. Herein we
      report the synthesis of mannose derivatives with one or two hydrophobic chains of
      different length, designed with the purpose of modifying the degree of exposure
      of the mannose when they were incorporated into liposomes. The interaction of
      glycovesicles with Con A was studied using: (i) agglutination assays; measured by
      dynamic laser light scattering (DLS); (ii) time resolved fluorescence methods and
      (iii) surface plasmon resonance (SPR) kinetic measurements. DLS data showed that
      an increase in hydrophobic chain length promotes a decrease of liposomes
      hydrodynamic radius. A longer hydrocarbon chain favors a deeper insertion into
      the bilayer and mannose moiety results less exposed at the surface to interact
      with lectin. Fluorescence experiments showed changes in the structure of
      glycovesicles due to the interaction with the protein. From SPR measurements the
      kinetic and equilibrium constants associated to the interaction of ConA with the
      different glycolipid synthetized were determined. The combination of SPR and
      fluorescence techniques allowed to study the interaction of Con A with mannosyl
      glycovesicles at three levels: at the surface, at the interface and deeper into
      the bilayer.

PMID- 28743090
TI  - NIR and UV-responsive degradable hyaluronic acid nanogels for CD44-targeted and
      remotely triggered intracellular doxorubicin delivery.
AB  - Hyaluronic acid (HA) is an endogenous polysaccharide that shows intrinsic
      targetability to CD44+ cancer cells. Here, we developed NIR and UV-responsive
      degradable nanogels from hyaluronic acid-g-7-N,N-diethylamino-4
      hydroxymethylcoumarin (HA-CM) for CD44 targeted and remotely controlled
      intracellular doxorubicin (DOX) delivery. Nanometer-sized HA-CM nanogels could
      readily load DOX, and both NIR and UV irradiation could significantly enhance DOX
      release from the nanogels, resulting from light-triggered cleavage of urethane
      bonds that connect CM to HA. MTT assays showed that DOX-loaded HA-CM nanogels
      combined with NIR irradiation induced much higher antitumor activity to MCF-7
      cells (CD44+) than to U-87MG cells (CD44-) and free HA pretreated MCF-7 cells.
      CLSM observations confirmed that DOX-loaded HA-CM nanogels were internalized by
      CD44+ cells via receptor mediated endocytosis mechanism, and intracellular DOX
      release was triggered by NIR. These HA-CM nanogels with easy preparation, CD44
      targetability and photo-controlled intracellular drug release are interesting for
      cancer chemotherapy.

PMID- 28743091
TI  - Performance comparison of two herbal and industrial medicines using nanoparticles
      with a starch/cellulose shell and alginate core for drug delivery: In vitro
      studies.
AB  - In this study, the performance of two kinds of industrial and herbal drugs
      encapsulated in nanoparticles with a shell of starch and cellulose and an
      alginate core were examined as a new technique for nanoparticle drug delivery.
      The test method involved creating a suspension of starch and alginate, which was
      then dried, mixed with cellulose, and heated to form core-shell nanoparticles.
      The industrial drug calcitonin and an extract of the herb Amaranthus retroflexcus
      L. were added separately and in combination to the nanoparticles, and the
      performance of each configuration was evaluated. Variables like shape, size of
      nanoparticle, and pH were examined for their effect in vitro. Response surface
      methodology (RSM) was employed for optimization of parameters. The properties of
      the nanoparticles were studied by scanning electron microscopy (SEM) and
      Ultraviolet-visible spectroscopy (UV-vis). The most optimal conditions for
      formation of the smallest nanoparticles were found to be pH 4 with a
      concentration of 0.15g starch, 0.04g alginate, and 0.01g cellulose, which
      resulted in a spherical nanoparticle size of 25.6-68.7nm. This novel method for
      helping bone regeneration offers a potentially major advance in the medical
      treatment of osteoporosis. The results of optimization indicated that the most
      optimal conditions of the tests were performed at pH 4, CA=0.04, CS=0.21, and
      CC=0.01. In acidic pH the size of nanoparticles was less than 100nm.

PMID- 28743092
TI  - Polycyclic aromatic hydrocarbons (PAHs) enrich their degrading genera and genes
      in human-impacted aquatic environments.
AB  - Bacterial degradation is an important clearance pathway for organic contaminants
      from highly human-impacted environments. However, it is not fully understood how
      organic contaminants are selected for degradation by bacteria and genes in
      aquatic environments. In this study, PAH degrading bacterial genera and PAH
      degradation-related genes (PAHDGs) in sediments collected from the Pearl River
      (PR), the Pearl River Estuary (PRE) and the South China Sea (SCS), among which
      there were distinct differences in anthropogenic impact, were analyzed using
      metagenomic approaches. The diversity and abundance of PAH degrading genera and
      PAHDGs in the PR were substantially higher than those in the PRE and the SCS and
      were significantly correlated with the total PAH concentration. PAHDGs involved
      with the three key processes of PAH degradation (ring cleavage, side chain and
      central aromatic processes) were significantly correlated with each other in the
      sediments. In particular, plasmid-related PAHDGs were abundant in the PR
      sediments, indicating plasmid-mediated horizontal transfer of these genes between
      bacteria or the overgrowth of the bacteria containing these plasmids under the
      stresses of PAHs. Our results suggest that PAH degrading bacteria and genes were
      rich in PAH-polluted aquatic environments, which could facilitate the removal of
      PAHs by bacteria.

PMID- 28743093
TI  - Development of a statistical oil spill model for risk assessment.
AB  - To gain a better understanding of the impacts from potential risk sources, we
      developed an oil spill model using probabilistic method, which simulates numerous
      oil spill trajectories under varying environmental conditions. The statistical
      results were quantified from hypothetical oil spills under multiple scenarios,
      including area affected probability, mean oil slick thickness, and duration of
      water surface exposed to floating oil. The three sub-indices together with marine
      area vulnerability are merged to compute the composite index, characterizing the
      spatial distribution of risk degree. Integral of the index can be used to
      identify the overall risk from an emission source. The developed model has been
      successfully applied in comparison to and selection of an appropriate oil port
      construction location adjacent to a marine protected area for Phoca largha in
      China. The results highlight the importance of selection of candidates before
      project construction, since that risk estimation from two adjacent potential
      sources may turn out to be significantly different regarding hydrodynamic
      conditions and eco-environmental sensitivity.

PMID- 28743094
TI  - A personalized medicine approach to the design of dry powder inhalers: Selecting
      the optimal amount of bypass.
AB  - In dry powder inhalers (DPIs) the patient's inhalation manoeuvre strongly
      influences the release of drug. Drug release from a DPI may also be influenced by
      the size of any air bypass incorporated in the device. If the amount of bypass is
      high less air flows through the entrainment geometry and the release rate is
      lower. In this study we propose to reduce the intra- and inter-patient variations
      of drug release by controlling the amount of air bypass in a DPI. A fast
      computational method is proposed that can predict how much bypass is needed for a
      specified drug delivery rate for a particular patient. This method uses a meta
      model which was constructed using multiphase computational fluid dynamic (CFD)
      simulations. The meta-model is applied in an optimization framework to predict
      the required amount of bypass needed for drug delivery that is similar to a
      desired target release behaviour. The meta-model was successfully validated by
      comparing its predictions to results from additional CFD simulations. The
      optimization framework has been applied to identify the optimal amount of bypass
      needed for fictitious sample inhalation manoeuvres in order to deliver a target
      powder release profile for two patients.

PMID- 28743095
TI  - A rapid and reliable method for discriminating rice products from different
      regions using MCX-based solid-phase extraction and DI-MS/MS-based metabolomics
      approach.
AB  - The expansion of the global rice marketplace ultimately raises concerns about
      authenticity control. Several analytical methods for differentiating the
      geographical origin of rice have been developed, yet a high-throughput method is
      still in demand. In this study, we developed a rapid approach using direct
      infusion-mass spectrometry (DI-MS) to distinguish rice products from different
      countries. Specifically, the elimination of the matrix effect by a
      polytetrafluoroethylene (PTFE) filter, a mixed-mode cation exchange (MCX) solid
      phase extraction (SPE) with 20% methanol, and an MCX SPE with 100% methanol were
      measured. Afterward, partial least squares discriminant analysis and random
      forests were applied to seek the optimal discrimination method. The results
      revealed that the combination of MCX SPE with 100% methanol and DI-MS in positive
      ion mode (accuracy=1.000, R2=0.916, Q2=0.720, B/W-based p-value=0.015) or the
      combination of MCX SPE with 20% methanol and targeted DI-MS/MS in positive ion
      mode (accuracy=1.000, R2=0.931, Q2=0.849, B/W-based p-value=0.002) showed the
      excellent discriminatory ability. Furthermore, differentially expressed
      metabolites including sodiated lysophosphatidylcholine, lysophosphatidylcholine,
      lysophosphatidylethanolamines and lysophosphatidylglycerol classes were found. In
      conclusion, our study provides a rapid and reliable platform for geographical
      discrimination of white rice and will contribute to the authenticity control of
      rice products.

PMID- 28743096
TI  - Osteoarthritis with permanent dislocation of the patella treated by total knee
      arthroplasty through a lateral approach: A report of two cases.
AB  - INTRODUCTION: Permanent dislocation of the patella (PDP) is a rare condition. In
      cases of PDP with tibiofemoral arthritis, total knee arthroplasty may be
      performed through a medial parapatellar approach with patellar realignment. In
      this article we present two cases of PDP with tibiofemoral osteoarthritis
      successfully treated via lateral approach TKA without any additional realignment
      procedure. We performed two total knee arthroplasties for PDP with lateral
      tibiofemoral arthritis through a lateral approach without any realignment
      procedure. Mobile bearing inserts were used to adjust rotational alignment. The
      patients showed improved functional outcomes (Japanese Orthopaedic Association
      Knee score and Oxford Knee Score), and improved range of motion. Three years
      postoperatively, the patellae remain stable without dislocation nor maltracking,
      maintaining a high functional score. CONCLUSION: To treat permanent dislocation
      of the patella with lateral knee osteoarthritis, TKA through a lateral approach
      have potential to be a new treatment option to achieve both a good outcome and
      repositioning of the patella.

PMID- 28743097
TI  - Less is more: an outcome assessment of patients operated for gallstone ileus
      without fistula treatment.
AB  - BACKGROUND: The treatment of gallstone ileus (GI) consists of surgical removal of
      the impacted bilestone with or without cholecystectomy and repair of the
      biliodigestive fistula. The objective of this study was to assess whether sparing
      patients a definitive biliary procedure adversely influenced the outcome.
      MATERIALS AND METHODS: Patients with a diagnosis of GI were reviewed. Two groups
      were identified: patients who underwent a definitive biliary procedure with
      relieving the intestinal obstruction (group 1/G1) and those who did not have a
      definitive biliary procedure (group 2/G2). In G2, patients were evaluated on long
      term follow-up for the risk of recurrent GI disease, cholecystitis, cholangitis
      and gallbladder cancer. RESULTS: Among 1075 patients admitted for small bowel
      obstruction, 20 (1.9%) were diagnosed with gallstone ileus. 3 (15%) of these
      belong to G1, 17 (85%) to G2. The overall postoperative morbidity rate was 35%
      (7/20) with one complication exceeding grade II in each group. No deaths were
      reported. Mean follow-up was 50 months. During follow-up, one of G2 patients had
      recurrent disease. No biliary tract infections or gallbladder cancer were
      identified. CONCLUSION: Enterolithotomy without fistula closure is confirmed to
      be safe and effective for the management of gallstone ileus both on a short- and
      long-term basis.

PMID- 28743098
TI  - Giant fibro epithelial polyp in a young girl: A rare case report.
AB  - INTRODUCTION: Fibro epithelial Polyp (FEP) is a polypoid outgrowth of epidermis
      and dermal fibro vascular tissue. This polyp is most commonly found in oral
      cavity, neck and axilla, though any skin fold may be affected like groin. These
      polyps are usually less than 5cm in size and rarely occur before 4th decade of
      life. Excision is the treatment of choice for such lesion. PRESENTATION OF CASE:
      A 20year old female patient presented with a large pedunculated mass originating
      from the left groin area extending up to the left knee joint. It measured 42cm in
      diameter. Surgical excision with primary closure was performed. We present this
      case because of its size and its occurrence at early age. DISCUSSION: In this
      case, a mass of 42*22*10cm in a 20years female has been described. This mass was
      diagnosed as a giant FEP, which is the largest size FEP reported, to the best of
      our knowledge. FEP usually occurs in females of reproductive age group but in the
      present case it occurred in a 20years old female. Various other lesions like
      leiomyomas, superficial angiomyxoma and neurofibroma mimic FEP. Complete excision
      with long term follow-up is the best option in such patient. CONCLUSION: Giant
      FEP is a benign lesion, sometimes it may be misdiagnosed as malignant lesion
      because of its larger size and occurrence in early age. Hence excisional biopsy
      is important to confirm the diagnosis.

PMID- 28743099
TI  - Laparoscopic surgery for colon cancer with intestinal malrotation in adults: Two
      case reports and review of literatures in Japan.
AB  - INTRODUCTION: Intestinal malrotation is a congenital anomaly, and its occurrence
      in adults is rare. Colon cancer with intestinal malrotation is far more rare. We
      herein report two cases of colon cancer with intestinal malrotation treated with
      laparoscopic surgery and reviewed the literatures in Japan. PRESENTATION OF
      CASES: Case 1 involved a 78-year-old man. Abdominal enhanced computed tomography
      (CT) showed that the tumor was located in the sigmoid colon. Intraoperatively,
      the cecum and ascending colon were located along the midline and the small
      intestine occupied the right side of the abdomen. The tumor was located in the
      cecum, and the patient was diagnosed with cecal cancer with intestinal
      malrotation. We performed laparoscopy-assisted ileocecal resection. Case 2
      involved a 81-year-old man. Colonoscopy revealed a laterally spreading tumor in
      the cecum. Intraoperatively, the position of the small intestine and the
      ascending colon was similar to case 1, and Ladd's band was found in front of the
      duodenum. Thus, we diagnosed the patient with a laterally spreading cecal tumor
      with intestinal malrotation and performed laparoscopy-assisted ileocecal
      resection. DISCUSSION: A review of the literature revealed 49 cases of colon
      cancer with intestinal malrotation and laparoscopic surgery performed at 30.6%.
      If laparoscopic mesenteric excision for colon cancer with intestinal malrotation
      is unsafe because of the abnormalities of the artery, mesenteric excision should
      be performed outside the body. CONCLUSION: If the intestinal malrotation is
      diagnosed preoperatively, 3D-CT angiography should be used to reveal the vascular
      anatomic anomalies for safe performance of laparoscopic surgery.

PMID- 28743100
TI  - Studies on secondary metabolite profiling, anti-inflammatory potential, in vitro
      photoprotective and skin-aging related enzyme inhibitory activities of Malaxis
      acuminata, a threatened orchid of nutraceutical importance.
AB  - Malaxis acuminata D. Don., a small, terrestrial orchid, is endemic to tropical
      Himalayas at an altitude of 1200-2000m asl. The dried pseudobulbs are important
      ingredients of century old ayurvedic drug 'Ashtavarga' and a polyherbal immune
      booster nutraceutical 'Chyavanprash', known to restore vigour, vitality and
      youthfulness. Considering tremendous medicinal importance of this threatened
      orchid species, a detailed study was undertaken for the first time to address its
      antioxidant potential, secondary metabolite contents and biological activities
      against skin-aging related enzymes (anti-collagenase, anti-elastase, anti
      tyrosinase and xanthine oxidase) and anti-inflammatory activity (5-lipoxygenase
      and hyaluronidase) in different plant parts of wild and in vitro-derived plants
      of M. acuminata. Methanolic leaf and stem extracts were further evaluated for in
      vitro photoprotective activity against UV-B and UV-A radiations. Furthermore,
      secondary metabolite profiling of various plant parts was carried out by Gas
      Chromatography Mass Spectrometry (GC-MS). A significantly higher antioxidant
      potential (DPPH, metal chelating and ABTS*+) with a comparative higher yield of
      secondary metabolites was observed in in vitro-derived plantlets as compared to
      the wild plants. Among various solvent systems used, methanolic leaf and stem
      extracts showed promising inhibitory activity against major skin aging-related
      enzymes and anti-inflammatory potential. Methanolic leaf and stem extracts of
      both wild and in vitro-derived plants showed promising photoprotective activity
      against UV-B and UV-A radiations in vitro with comparatively higher sun
      protection factor (SPF). Furthermore, GC-MS analysis of methanolic extracts of
      leaves and stems of wild as well as in vitro-derived plantlets revealed presence
      of many bioactive metabolites such as, dietary fatty acids, alpha-hydroxy acids,
      phenolic acids, sterols, amino acids, sugars and glycosides which substantially
      explain the use of M. acuminata as one of the potential rejuvenator and anti
      aging ingredient in many Ayurvedic formulations.

PMID- 28743101
TI  - In silico locating the immune-reactive segments of Lepidium draba peroxidase and
      designing a less immune-reactive enzyme derivative.
AB  - Peroxidases have broad applications in industry, environmental as well as
      pharmaceutical and diagnosis. Recently applicability of peroxidases in cancer
      therapy was mentioned. In the present study, a horseradish peroxidase homologue
      from Lepidium draba was subjected to in silico analyzes aiming at identifying and
      locating immune-reactive regions. A derivative sequence with decreased
      immunogenicity and increased stability also suggested. The tertiary structure of
      the enzyme was predicted. The functional and structural importance of residues
      was annotated as well as the conservatory status of each residue. The immune
      dominant regions of protein were predicted with various software. N-terminal 4
      residues, NFSHTGL (186-192), PRNGN (210-214), PLVRAYADGTQKFFN (261-275), and last
      4 residues in C-terminal were predicted to be the consensus immunogenic segments
      of L. draba peroxidase. The modifications were applied to wild type sequence in
      order to mitigate its immune-reactiveness. The modifications were based on
      predicted energetic status of residues and naturally occurred amino acids in each
      position of the enzyme sequence, extracted from alignment file of 150 homologous
      peroxidases. The new enzyme derivative is predicted to be less immune-reactive
      and more stable. Thus the sequence is better suited to therapeutic applications.

PMID- 28743102
TI  - Incidence of delirium after cardiac surgery: protocol for the DELIRIUM-CS Canada
      cross-sectional cohort study.
AB  - BACKGROUND: Delirium is a recognized complication of cardiac surgery and is the
      focus of increasing attention owing to its negative effect on postoperative
      outcomes. However, little is known about the actual incidence of delirium
      following cardiac surgery, with published rates ranging widely, from 3%-78%. We
      describe the protocol for the DELIRIUM-CS Canada study, which will use validated
      and easily implementable bedside tools to determine the incidence of
      postoperative delirium in a contemporary cardiac surgery population. We
      hypothesize that delirium, identified through a systematic and standardized
      screening protocol, is a highly prevalent, though variable, condition following
      cardiac surgery. METHODS: The DELIRIUM-CS Canada study is a multicentre cross
      sectional cohort study. Over a 3-month period, all patients undergoing major
      cardiac surgical procedures at 10 participating centres will be screened for
      postoperative delirium by means of the Intensive Care Delirium Screening
      Checklist or the Confusion Assessment Method for the Intensive Care Unit.
      Delirium screening will be conducted for 7 days following the date of surgery or
      until the initial discharge from the intensive care unit. In addition to
      reporting an overall rate of delirium, we will report unadjusted and adjusted
      incidence rates of delirium by institution and for the entire cohort. Risk
      adjustment will be performed with the use of multivariate regression modelling
      techniques. INTERPRETATION: The results of this study will provide valuable
      insight into the true burden of delirium among patients having undergone a major
      cardiac surgical procedure in the current era. This is the first step in creating
      a multifaceted delirium prevention/treatment clinical pathway for patients
      undergoing cardiac surgery. Trial registration: ClinicalTrials.gov, no.
      NCT02206880.

PMID- 28743103
TI  - Lanthanum Chloride Inhibits LPS Mediated Expressions of Pro-Inflammatory
      Cytokines and Adhesion Molecules in HUVECs: Involvement of NF-kappaB-Jmjd3
      Signaling.
AB  - BACKGROUND/AIMS: To investigate the regulation of LaCl3 on lipopolysaccharides
      (LPS)-induced pro-inflammatory cytokines and adhesion molecules in human
      umbilical vein endothelial cells (HUVECs). METHODS: Primary cultured HUVECs were
      pretreated with 2.5 uM LaCl3 for 30 min followed by 1 ug/ml LPS for 2 h. Pro
      inflammatory cytokine and adhesion molecule expressions were determined by real
      time RT-PCR and ELISA. NF-kappaB/p65 nuclear translocation was examined by
      immunofluorescence and immuno-blot, and its DNA-binding activity was measured by
      chemiluminescence. Recruitment of NF-kappaB/p65, Jmjd3, and H3K27me3 to gene
      promoter regions was determined by ChIP-qPCR. RESULTS: LaCl3 exhibited no
      cytotoxic effects to primary HUVECs at concentrations <= 50 uM. LPS-mediated TNF
      alpha, IL-1beta, IL-6, MMP-9, and ICAM-1 production, nuclear translocation, and
      DNA-binding activity of NF-kappaB/p65, as well as Jmjd3 expression, were all
      reduced significantly by LaCl3. Furthermore, LaCl3 treatment significantly
      impaired LPS-induced enrichment of NF-kappaB/p65 to the promoter regions of TNF
      alpha, MMP-9, IL-1beta, ICAM-1, and IL-6; and of Jmjd3 to the promoter regions of
      TNF-alpha, MMP-9, IL-1beta, and IL-6. H3K27me3 abundance in the promoter regions
      of TNF-alpha and ICAM-1 increased significantly in following LaCl3 treatment.
      CONCLUSION: LaCl3 inhibits pro-inflammatory cytokine and adhesion molecule
      expressions induced by LPS in HUVECs. NF-kappaB and histone demethylase Jmjd3 are
      involved in this effect.

PMID- 28743104
TI  - Self-Care Activities among People with Multiple Sclerosis in Denmark: Use and
      User Characteristics.
AB  - BACKGROUND: People with multiple sclerosis (PwMS) are known to use a wide range
      of medical and non-medical treatments. This study aims at investigating the use
      of self-care activities within this patient group. MATERIAL AND METHODS: The
      study follows a descriptive cross-sectional design based on an online survey
      among members of the Danish Multiple Sclerosis Society's permanent respondent
      panel. RESULTS: The results of the study indicate that the respondents carry out
      a wide variety of self-care activities. These activities comprise conventional
      activities as well as complementary and alternative medicine (CAM)-based
      activities. The self-care activities are mainly kept up for non-specific and
      preventive purposes, with primarily personal or non-specific issues as the
      primary source of inspiration. Comparative analyses indicate that respondents
      with a low level of self-care more often are men, belong to the young age group
      and have a low level of education, a low level of self-assessed state of health,
      a low level of self-assessed quality of life (QoL), and an unknown subdiagnosis.
      Respondents with a high level of self-care are more often women and have a high
      level of self-assessed QoL. CONCLUSIONS: A wide variety of self-care activities
      are carried out by PwMS, comprising conventional as well as CAM-based activities.
      The purposes of such activities are manifold, but they are mainly of non-specific
      and preventive nature. Differences in background characteristics exist between
      groups of low and high levels of self-care.

PMID- 28743105
TI  - Statistical Interactions from a Growth Curve Perspective.
AB  - Logistic regression is widely used to evaluate the association between risk
      factors and a binary outcome. The logistic curve is symmetric around its point of
      inflection. Alternative families of curves, such as the additive Gompertz or
      Guerrero-Johnson models, have been proposed in various scenarios due to their
      asymmetry: disease risk may initially increase rapidly and be followed by a
      longer period where the rate of growth slowly decreases. When modeling binary
      outcomes in relation to risk factors, an additive logistic model may not provide
      a good fit to the data. Suppose the outcome and an additive function of the risk
      factors are indeed related through an asymmetric function, but we model the
      relationship using a logistic function. We illustrate - both from a mathematical
      framework and through a simulation-based evaluation - that higher-order terms,
      such as pairwise interactions and quadratic terms, may be required in a logistic
      regression model to obtain a good fit to the data. Importantly, as significant
      higher-order terms may be a manifestation of model misspecification, these terms
      should be cautiously interpreted; a more pragmatic approach is to develop
      contrasts of disease risk coming from a good fitting model. We illustrate these
      concepts in 2 cohort studies examining early death for late-stage colorectal and
      pancreatic cancer cases, and 2 case-control studies investigating NAT2
      acetylation, smoking, and advanced colorectal adenoma and bladder cancer.

PMID- 28743106
TI  - The Complexities of Defining a Complex Karyotype in Hematological Malignancies: A
      Need for Standardization?

PMID- 28743107
TI  - A "Prozone-Like" Effect Influences the Efficacy of the Monoclonal Antibody ABT
      700 against the Hepatocyte Growth Factor Receptor.
AB  - ABT-700 is a therapeutic antibody against the hepatocyte growth factor receptor
      (MET). At doses or regimens that lead to exposures exceeding optimum in vivo, the
      efficacy of ABT-700 is unexpectedly reduced. We hypothesized that this reduction
      in efficacy was due to a "prozone-like" effect in vivo. A prozone-like effect,
      which is a reduction in efficacy beyond optimum exposure, is caused due a
      mechanism similar to the generation of false negative flocculation tests by
      excessive antibody titres. In vitro, we demonstrate that at higher ABT-700
      concentrations, this "prozone-like" effect is mediated by a progressive
      conversion from bivalent to ineffective monovalent binding of the antibody. In
      vivo, the efficacy of ABT-700 is dependent on an optimum range of exposure as
      well. Our data suggest that the "prozone-like" effect is operative and
      independent of target expression. ABT-700 dose, regimen, exposure, and tumor
      burden are interdependent variables influencing the "prozone-like" effect and
      mediating and in vivo efficacy. By optimization of dosage and regimen we
      demonstrate that the "prozone-like" effect can be alleviated and ABT-700 efficacy
      at varying tumor loads can be further extended in combination with cisplatin. Our
      results suggest that optimization of exposure taking tumor burden into account
      may alleviate "prozone-like" effects without compromising efficacy.

PMID- 28743108
TI  - High-Density Lipoprotein Cholesterol Level Relates to Working Memory, Immediate
      and Delayed Cued Recall in Brazilian Older Adults: The Role of Cognitive Reserve.
AB  - AIMS: The present study set out to investigate the relation of the high-density
      lipoprotein cholesterol (HDL-C) level to cognitive performance and its interplay
      with key markers of cognitive reserve in a large sample of older adults. METHODS:
      We assessed tests of working memory, immediate and delayed cued recall in 701
      older adults from Amazonas, Brazil. The HDL-C level was derived from fasting
      blood samples. In addition, we interviewed individuals on their education, past
      occupation, and cognitive leisure activity. RESULTS: A critically low HDL-C level
      (<40 mg/dL) was significantly related to lower performance in working memory,
      immediate and delayed cued recall. Moderation analyses suggested that the
      relations of the HDL-C level to working memory and delayed cued recall were
      negligible in individuals with longer education, a higher cognitive level of the
      job, and greater engagement in cognitive leisure activity. CONCLUSION: Cognitive
      reserve accumulated during the life course may reduce the detrimental influences
      of a critically low HDL-C level on cognitive functioning in old age.

PMID- 28743109
TI  - Robot-Assisted Vesico-Vaginal Fistula Repair: Our Technique and Review of the
      Literature.
AB  - OBJECTIVE: Our first objective was to report our experience on robot-assisted
      vesico-vaginal fistula (VVF) repair after radical surgery for gynecologic
      malignancies without omental flap interposition using a da Vinci robotic system.
      The second objective was to critically review the literature in order to analyze
      surgical solutions used to avoid repair failure. MATERIALS AND METHODS: Five
      patients with VVF diagnosed after previous open surgery for gynecologic
      malignancies referred to our tertiary institutions were selected. After an
      adequate oncologic follow-up, based on the fistula diameter and conservative
      management failure, robotic surgery repair was proposed. A bivalve 2-layer
      suturing technique was carried out without tissue interpositions; omentum was not
      available secondary to previous surgery including hysterectomy, ovaryectomy, and
      omentectomy and citoreductive peritoneomectomy. A systematic review of the
      literature was performed in December 2016 using the PubMed database with the
      following keywords: robotic, robot-assisted, vesico-vaginal, fistula repair.
      RESULTS: Median age was 62 years (range 55-71) bearing long-lasting VVF were
      referred to our divisions. Median fistula diameter was 5 mm (range 3-8 mm).
      Fistula site was the trigone and identified during cystoscopy near the mid-line,
      left, and right urether meatus, respectively. The median overall and console
      operatory time were 250 and 120 min, respectively. Blood loss was insignificant
      (median 40 mL) and the median length of stay was 7 days without any complication.
      Ten papers were found fulfilling the mentioned criteria, from which 6 were case
      reports, single or multiple, accounting for the overall 41 robotic-approach
      operated patients. CONCLUSION: The quality of the dissection and suture
      associated with efficient urine drainage are in our opinion the key elements of
      the success of our technique, which can be performed even without omentum or
      other tissue flap or graft interposition.

PMID- 28743110
TI  - Clinical, Endocrine, and Molecular Genetic Analysis of a Large Cohort of Saudi
      Arabian Patients with Laron Syndrome.
AB  - BACKGROUND/AIMS: Laron syndrome (LS) is an autosomal recessive disease
      characterized by marked short stature and very low serum IGF-1 and IGFBP-3
      levels. This study assessed the clinical and endocrine features alongside
      determining the growth hormone receptor gene (GHR) mutation in Saudi Arabian
      patients with LS in order to establish whether or not a genotype/phenotype
      correlation is evident in this large cohort. SUBJECTS AND METHODS: A total of 40
      Saudi Arabian patients with a suspected diagnosis of LS were recruited and
      subjected to a full clinical and endocrine investigation together with direct
      sequencing of the coding regions of the GHR gene. RESULTS: GHR mutations were
      identified in 34 patients from 22 separate nuclear families. All 34 molecularly
      confirmed patients had the typical clinical and endocrinological manifestations
      of LS. Eleven different mutations (9 previously unreported) were detected in this
      cohort of patients, all inherited in an autosomal recessive homozygous form. No
      genotype/phenotype correlation was apparent. CONCLUSION: The identification of
      pathogenic mutations causing LS will be of tremendous use for the molecular
      diagnosis of patients in Saudi Arabia and the region in general, with respect to
      prevention of this disease in the forms of future carrier testing, prenatal
      testing, premarital screening and preimplantation genetic diagnosis.

PMID- 28743111
TI  - Sleep and Olfaction among Older Adults.
AB  - BACKGROUND: Sleep and olfaction are both critical physiological processes that
      tend to worsen with age. Decline in olfaction can be an early indicator of
      neurodegenerative diseases, whereas poor sleep quality is associated with reduced
      physical and mental health. Given associations with aging-related health
      declines, we explored whether variations in sleep were associated with olfactory
      function among older adults. METHODS: We assessed the relationship between sleep
      characteristics and olfaction among 354 community-dwelling older adults.
      Olfaction was measured using a validated field and survey research tool. Sleep
      characteristics were measured using wrist actigraphy and with self-report of
      sleep problems. We fit structural equation models of latent constructs of
      olfaction based on olfactory task items and let this be a function of each sleep
      characteristic. RESULTS: Actigraph sleep quality measures were associated with
      odor identification, but not with odor sensitivity. Longer duration sleepers had
      worse odor sensitivity compared to medium (58 h) sleepers, but sleep duration was
      not associated with odor identification. Reported sleep problems and reported
      usual duration were not associated with olfaction. CONCLUSIONS: Diminished sleep
      quality was associated with reduced capacity to identify odors. Determining
      whether this is a causal association will require further study and longitudinal
      data.

PMID- 28743112
TI  - MicroRNA-302b-3p Suppresses Cell Proliferation Through AKT Pathway by Targeting
      IGF-1R in Human Gastric Cancer.
AB  - BACKGROUND/AIMS: MiR-302b is a major microRNA found in human embryonic stem cells
      and induced pluripotent stem cells. However, its function in gastric cancer
      progression remains unclear. METHODS: Quantitative reverse transcription-PCR was
      performed to detect the expression levels of miR-302b-3p in gastric cancer
      tissues. MTT, colony formation, and flow cytometer analyses were conducted to
      explore the function of miR-302b-3p in MKN-45/SGC-7901 cells. A dual-luciferase
      reporter was used to validate the bioinformatics-predicted target gene of miR
      302b-3p. Western blotting and RNA interference were used to evaluate the
      expression of the AKT signaling pathway and determine the mechanisms underlying
      miR-302b-3p-induced anti-tumor effects. RESULTS: MiR-302b-3p expression was
      decreased in gastric cancer tissues and cell lines. Enforced expression of miR
      302b suppressed cell proliferation and cell cycle G1-S transition and induced
      apoptosis. IGF-1R was found to be a direct target of miR-302b-3p, and silencing
      of IGF-1R resulted in the same biological effects as those induced by miR-302b-3p
      overexpression in gastric cancer cells. Importantly, both overexpression of miR
      302b-3p and silencing of IGF-1R decreased AKT phosphorylation, which modulated
      AKT related cell cycle regulators (cyclin A2, cyclin D1, CDK2, and CDk6) and
      apoptotic protein Bax/Bcl-2. CONCLUSION: These results indicate the tumor
      suppressor role of miR-302b-3p in the pathogenesis of gastric cancer.

PMID- 28743113
TI  - Pulmonary Hypertension in a Large Cohort with Hereditary Hemorrhagic
      Telangiectasia.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder
      characterized by arteriovenous malformations in the brain, liver, and lungs.
      Pulmonary hypertension (PH) is increasingly recognized as a severe complication
      of HHT. However, there are no studies describing the prevalence of PH in HHT
      compared to HHT-negative controls. OBJECTIVE: To assess the estimated prevalence
      of PH in patients with HHT compared to HHT-negative controls. METHODS: All
      consecutive subjects screened for HHT with available genetic testing and
      echocardiography-based peak tricuspid regurgitation velocity (TRV) measurement
      were included. Increased-probability PH was defined as a TRV >2.8 m/s. RESULTS:
      In 578 subjects, both echocardiography and genetic testing were available. A
      reliable TRV was measured in 383 (66.3%), of whom 127 had HHT type 1 (HHT1), 150
      had HHT type 2 (HHT2), and 106 were HHT-negative controls, with a mean TRV of 2.3
      +/- 0.4, 2.4 +/- 0.5, and 2.2 +/- 0.3 m/s, respectively (p = 0.008 and p < 0.001
      vs. controls). Increased-probability PH was found in 42 subjects (8.7% in HHT1,
      18.0% in HHT2, and 3.8% in HHT-negative controls). HHT2 and hepatic arteriovenous
      malformations (HAVMs) were the most important predictors for increased
      probability PH (odds ratio 5.6, p = 0.002, and odds ratio 11.3, p < 0.001,
      respectively). Heritable pulmonary arterial hypertension (HPAH) was diagnosed in
      2 patients (0.7%) and only found in HHT2 (1.3%). CONCLUSION: The estimated
      prevalence of PH is higher in HHT patients compared to HHT-negative controls.
      This increase is especially present in HHT2 and mainly associated with the
      presence of HAVMs. HPAH appears to be rare in HHT patients and was only diagnosed
      in HHT2.

PMID- 28743114
TI  - Cervical Alpha-Actinin-4 Is Upregulated in Women with Threatened Preterm Labor
      and Microbial Invasion of the Amniotic Cavity.
AB  - OBJECTIVE: To characterize the proteome profile of women with threatened preterm
      labor (PTL) below 34;0 weeks with and without microbial invasion of the amniotic
      cavity (MIAC) using mass spectrometry in the amniotic fluid (AF) and Western blot
      analysis in the cervical mucus and the vaginal fluid. SUBJECTS AND METHODS: In
      the discovery phase, a case-control study including 8 women with MIAC and 7
      without matched for gestational age at sampling was performed. Proteomic profile
      characterization was done using the LTQ VELOS Orbitrap mass spectrometer in the
      AF. In the validation phase, a selection of the proteins differentially expressed
      by mass spectrometry in the genital samples of a prospective cohort of 109 women
      was validated by Western blot analysis. RESULTS: In the discovery phase, the mass
      spectrometry analysis identified a total of 444 proteins. Sixteen were chosen for
      validation, being involved in defense (calgranulin A, B, C, C-reactive protein),
      cytoskeletal remodeling (alpha-actinin-4 [ACTN-4], plastin-2, alpha2-antiplasmin,
      vitronectin), metabolism (cystatin-beta, glucose 6 phosphate isomerase,
      glutathione S-transferase, prostaglandin D2 synthase, corticosteroid-binding
      globulin), and vascular (alpha1-antichymotrypsin, hemopexin, endosialin)
      pathways. In the validation phase, cervical ACTN-4 was the only significantly
      upregulated protein in women with MIAC with an odds ratio of 6.8 (p = 0.002).
      CONCLUSIONS: Cervical ACTN-4 was significantly upregulated in the group of women
      with PTL with MIAC.

PMID- 28743115
TI  - Cerebrospinal Fluid Levels of 14-3-3 Gamma: What Does It Tell Us About Sporadic
      Creutzfeldt-Jakob Disease?
AB  - Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) can be supported by the
      analysis of Tau and 14-3-3 in the cerebrospinal fluid (CSF). In this short
      report, we report about a retrospective analysis performed on 2,296 routinely
      collected CSF samples, and 44 samples with a ratio of phosphoTau181/Tau <0.075
      were selected. Analysis was performed with a novel 14-3-3 gamma CircuLex Elisa.
      We show that control levels were around 6,000 AU/mL and samples from Alzheimer
      patients were not different from those collected from healthy controls. Four
      cases of verified CJD had 14-3-3 CSF levels of >100,000 AU/mL, while 10 out of 12
      suspected CJD samples with 14-3-3 CSF levels between 50,000-100,000 AU/mL were
      CJD positive. All samples with 14-3-3 levels between 15,000 and 50,000 AU/mL were
      not CJD cases but disorders with complex neuropathology. In conclusion, our data
      suggests that in CSF samples with a phospho-Tau-181/Tau ratio <0.075 CSF levels
      of 14-3-3 should be analyzed. Our data suggests a very high risk for CJD with 14
      3-3 levels above 100,000 AU/mL and a probable diagnosis of CJD based on
      laboratory parameters above 50,000 AU/mL.

PMID- 28743117
TI  - Erratum.

PMID- 28743116
TI  - The Role of Tumoral FOXP3 on Cell Proliferation, Migration, and Invasion in
      Gastric Cancer.
AB  - BACKGROUND/AIMS: There is little published data on the role of FOXP3 in gastric
      cancer. METHODS: FOXP3 expression and localization in gastric cancer tissues and
      cells were examined by immunohistochemistry, RT-PCR, flow cytometry, western
      blot, and laser confocal microscopy. CCK8, plate clone, wound healing, and
      transwell insert assays were performed for gastric cancer cells. Potential
      molecules and signaling pathways were screened using high-throughput
      transcriptome sequencing. RESULTS: FOXP3 expression in gastric cancer tissues was
      higher than that in para-carcinoma tissues. It was restricted to the cytoplasm of
      para-carcinoma tissues, but was observed in the cytoplasm or/and nuclei of
      gastric cancer tissues. FOXP3 expression was positively correlated with
      pathological grading, and was detected in gastric cancer and GES-1 cells, where
      it was expressed in the cytoplasm alone, or in both the cytoplasm and the
      nucleus. FOXP3 overexpression promoted cell proliferation, migration, and
      invasion, while FOXP3 knockdown suppressed these effects. Furthermore, RT-PCR and
      ELISA confirmed that FOXP3 upregulation resulted in increased TGF-beta expression
      and secretion in gastric cancer cells. CONCLUSION: FOXP3 expression was
      associated with degree of gastric cancer differentiation. In addition,
      upregulated and ectopic tumoral FOXP3 can promote gastric cancer proliferation,
      migration, and invasion, partly through the TGF-beta pathway.

PMID- 28743118
TI  - Disappearance of Bone Marrow Fibrosis in a Patient with Chronic Myeloid Leukemia
      Treated with Dasatinib.
AB  - We report a case of a chronic myeloid leukemia patient showing progressive bone
      marrow fibrosis and anemia during imatinib therapy. Given the loss of major
      molecular response, we switched treatment to dasatinib 100 mg daily, observing a
      reduction in BCR-ABL transcript, a significant improvement of anemia, and a
      gradual disappearance of fibrosis. After 7 years of dasatinib therapy the patient
      maintains a complete cytogenetic response and a deep molecular response; the last
      bone biopsy confirmed the absence of fibrosis.

PMID- 28743119
TI  - The 37th Annual Meeting of the J.B. Johnston Club for Evolutionary Neuroscience
      and the 29th Annual Karger Workshop in Evolutionary Neuroscience: Abstracts.

PMID- 28743120
TI  - Everolimus in Combination with Octreotide Long-Acting Repeatable in a First-Line
      Setting for Patients with Neuroendocrine Tumors: A 5-Year Update.
AB  - BACKGROUND: We previously presented data of this multicentric, phase II study
      showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced
      neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe
      treatment. We now present updated data at 5 years. METHODS: Patients with
      advanced well-differentiated, previously untreated neuroendocrine tumors of the
      gastroenteropancreatic tract and of the lung received octreotide LAR 30 mg plus
      everolimus 10 mg/day. The primary endpoint was the objective response rate (ORR).
      We performed an analysis of "long responder" patients and of time to progression
      (TTP) and overall survival (OS) at 5 years. RESULTS: Fifty patients were
      enrolled; the primary tumor site was: pancreas (14 patients), lung (11 patients),
      ileum (9 patients), jejunum/duodenum (2 patients), and unknown (14 patients).
      Seventeen (34%) of these patients have received treatment for more than 2 years.
      The median exposure to study drugs was 519.5 days (range 48-2,024). Currently 3
      patients are still in treatment. The ORR (partial response + complete response)
      was 18% (95% confidence interval [CI] 7.4-28.6): complete response 1 patient
      (2%), partial response 8 patients (16%), stable disease 37 patients (74%). The
      median TTP was 33.6 months (95% CI 18.7-41.2) and the median OS was 61.0 months
      (95% CI 49.8-not reached). CONCLUSION: In this update of clinical outcome at 5
      year follow-up, everolimus plus octreotide has been shown to be active in
      advanced NENs. The current analysis showed a further prolongation of TTP and a
      long exposure to the study drug without major side effects in the long term.

PMID- 28743121
TI  - A Severe Case of Hemoglobin H Disease due to Compound Heterozygosity for Deletion
      of the Major alpha-Globin Regulatory Element (MCS-R2) and alpha0-Thalassemia.

PMID- 28743122
TI  - Utility of Transbronchial Lung Cryobiopsy in Non-Interstitial Diseases.
AB  - BACKGROUND: Transbronchial lung cryobiopsy (TLCB), performed with a flexible
      cryoprobe, is an interventional pulmonology procedure that has proved its
      diagnostic value for interstitial pulmonary disease. However, it has not been
      explored extensively as a diagnostic tool for patients with non-interstitial lung
      pathology, including infectious and malignant diseases. OBJECTIVE: To evaluate
      the diagnostic yield and safety of an interventional pulmonology approach that
      integrates TLCB and bronchoalveolar lavage (BAL) for the diagnosis of non
      interstitial pulmonary disease. METHODS: TLCB and BAL were performed under
      general anesthesia through the same bronchoscopic access on 103 adult patients
      (including immunocompromised HIV+ individuals) with clinical/radiological
      evidence of non-interstitial lung disease admitted to the Interventional
      Pulmonology Service between May 2015 and April 2016. Samples obtained were sent
      to pathology and microbiology laboratories for standard diagnostic analysis.
      RESULTS: Samples of TLCB allowed the diagnosis of 75.7% of patients, while 39.8%
      were diagnosed from BAL. The global diagnostic yield from the dual sampling was
      92.2%. TLCB allowed the diagnosis of 94.7% of cancer cases and 60.0% of
      infectious cases, while BAL samples identified 77.5% of infectious cases and
      21.2% of malignant lesions. The incidence of complications was 4.9% with full
      recovery in all cases. CONCLUSIONS: Simultaneous TLCB and BAL constitute a safe
      and useful diagnostic procedure for non-interstitial pulmonary disease, with a
      global diagnostic yield of 92.2%. Complementary advantages of samples obtained by
      each technique result in a robust diagnostic strategy for infectious and
      malignant disease in adults, including HIV+ individuals.

PMID- 28743123
TI  - Erratum.

PMID- 28743124
TI  - The Role of Discoidin Domain Receptor 1 in Inflammation, Fibrosis and Renal
      Disease.
AB  - Discoidin domain receptors (DDRs) are a family of 2 non-integrin collagen
      receptors, DDR1 and DDR2, which display a tyrosine kinase activity. They are
      mainly expressed during embryonic development and their role during adulthood is
      very limited. DDR1 has been widely studied in several types of cancers, in
      atherosclerosis and fibrosis, but also in chronic kidney disease (CKD). This
      review focuses on the role of DDR1 in chronic nephropathies and on the effect of
      its deletion in the pathological processes involved in renal disease progression.
      DDR1 was shown to be de novo expressed in several models of experimental CKD. Its
      genetic or pharmaco-genetic inhibition led to the preservation of renal structure
      and function, and to decreased inflammatory influx and fibrosis. Furthermore,
      delayed pharmaco-genetic inhibition of DDR1 led to significant protection in
      models of renal disease. These results demonstrate the involvement of DDR1 in
      inflammatory and fibrotic processes occurring during CKD and the beneficial
      effect of its inhibition. Thus, DDR1 could be an interesting therapeutic target
      to treat renal pathologies.

PMID- 28743125
TI  - Surfactant Protein B Suppresses Lung Cancer Progression by Inhibiting Secretory
      Phospholipase A2 Activity and Arachidonic Acid Production.
AB  - BACKGROUND/AIMS: Radiotherapy is applied to patients with inoperable cancer types
      including advanced stage non-small cell lung cancer (NSCLC) and radioresistance
      functions as a critical obstacle in radiotherapy. This study was aimed to
      investigate the mechanism of radioresistance regulated by surfactant protein B
      (SP-B). METHODS: To investigate the role of SP-B in radioresistance, DeltaSFTPB
      A549 cell line was established and SP-B expression was analyzed. In response to
      ionizing radiation (IR), the change of SP-B expression was analyzed in A549 and
      NCI-H441 cell lines. Conditioned media (CM) from NSCLC cells were utilized to
      evaluate the downstream signaling pathway. The in vivo effects of SP-B were
      assessed through mouse xenograft model with intratumoral injection of CM.
      RESULTS: In response to IR, NSCLC cell lines showed decreased SP-B regulated by
      the TGF-beta signaling and decreased SP-B stimulated cell survival and epithelial
      mesenchymal transition. Treatment with CM from irradiated cells activated sPLA2,
      enhanced protein kinase Cdelta-MAPKs signaling pathway, and increased arachidonic
      acid production. We confirmed the in vivo roles of SP-B through mouse xenograft
      model. CONCLUSION: Our results revealed that down-regulation of SP-B was involved
      in the radiation-induced metastatic conversion of NSCLC and provided evidence
      that SP-B acted as a suppressor of NSCLC progression.

PMID- 28743126
TI  - Frontal Cortex and Hippocampal gamma-Secretase Activating Protein Levels in
      Prodromal Alzheimer Disease.
AB  - BACKGROUND: beta-Amyloid (Abeta) is the product of concerted cleavage of the
      amyloid precursor protein (APP) by beta- and gamma-secretases. However, the
      molecular mechanisms that regulate this process are not well understood.
      Recently, evidence was reported that gamma-secretase activating protein (GSAP, 16
      kDa), derived from a larger precursor protein (98 kDa), plays a role in Abeta
      metabolism through a mechanism involving its interaction with both gamma
      secretase and APP. However, a detailed evaluation of GSAP protein levels and
      their association with clinical and neuropathological variables are lacking
      during the clinical progression of Alzheimer disease (AD). METHODS: We quantified
      levels of the GSAP precursor (98 kDa) and its active form (16 kDa) in the frontal
      cortex and hippocampus, areas displaying extensive Abeta and neurofibrillary
      tangle (NFT) pathology, in subjects who came to autopsy with a premortem clinical
      diagnosis of noncognitive impairment, mild cognitive impairment, mild to moderate
      AD, and severe AD using Western blotting. RESULTS: Analysis found that 98-kDa
      GSAP levels were increased, while those of 16 kDa were reduced in the frontal
      cortex of severe-AD subjects. By contrast, GSAP levels remained stable in the
      hippocampus. Frontal cortex and hippocampal GSAP 98- and 16-kDa levels were not
      associated with Abeta, NFT, and neuropathological criteria across clinical
      groups. Interestingly, only neocortical 98-kDa GSAP values showed a significant
      correlation with the Mini-Mental State Examination and episodic memory scores.
      CONCLUSIONS: These data demonstrate that GSAP proteins are differentially
      dysregulated in severe AD, but only the full-length form was associated with
      cognitive test scores in AD.

PMID- 28743127
TI  - A Rare Presentation of Immunoglobulin A Nephropathy: Acute Kidney Injury.
AB  - BACKGROUND: Acute kidney injury (AKI) is known as an uncommon presentation in
      immunoglobulin A nephropathy (IgAN). The aim of our study was to analyze the
      clinical data and biopsy findings in IgAN patients presenting with AKI. METHODS:
      We performed a retrospective analysis of all subjects who had biopsy-proven IgAN
      and presented with AKI during June 2002 September 2015. The following data were
      obtained from medical records. RESULTS: A total of 15 patients of 123 patients
      (12.2%) with primary IgAN admitted with AKI. Patients were generally male
      (73.3%), with a median age of 38 (interquartile range; IQR, 2,944) years. The
      serum creatinine at admission was above the normal range (median 2.3 [IQR,
      2.14.7] mg/dL]). On histology, cellular/fibrocellular crescents were present in 6
      patients. In most cases (53.3%), pathologic abnormalities associated with acute
      tubular injury/necrosis were defined. Red blood cell casts in tubules were
      present in 6 cases (40%). In all cases, interstitial mixed inflammatory cell
      infiltration was observed. In 4 cases, admixed eosinophils were also found. In 3
      patients, biopsy specimens showed acute thrombotic microangiopathy lesions (20%).
      Median follow-up time was 13 (IQR, 346) months. Six patients (40%) progressed to
      end-stage renal disease (ESRD). Among patients diagnosed with primary IgAN and
      presenting without AKI, only 4 patients progressed to ESRD. The proportion of
      patients who progressed to ESRD presenting with AKI was significantly higher than
      the patients presenting without AKI (p = 0.000). CONCLUSIONS: In conclusion, AKI
      complicates IgAN more often.

PMID- 28743129
TI  - Fibroblast Growth Factor 23 Predicts Mortality and End-Stage Renal Disease in a
      Canadian Asian Population with Chronic Kidney Disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a leading cause of morbidity and
      mortality. Biomarkers that predict end-stage renal disease (ESRD) and/or
      mortality could usher in new therapeutics to halt this onslaught. While
      fibroblast growth factor (FGF)23 can predict both ESRD and mortality, it has not
      been studied in North American CKD patients of Asian ethnicity. METHOD: This is a
      prospective investigation about the role of FGF23 in 998 Canadian patients of
      Asian descent with CKD defined by an estimated glomerular filtration rate (eGFR)
      <60 mL/min/m2 and followed up for 3 years. RESULTS: The mean age of patients was
      68.9 years and 68.3% were males. The mean (range) eGFR, and median FGF23 were
      40.2 (11.0-59.0) mL/min and 154.1 (7.0-7,823.0) RU/mL, respectively. Over the 3
      years, higher values of FGF23 levels at baseline were associated with higher risk
      of ESRD (hazard ratio [HR] for log[Fgf23] = 2.16 [95% CI 1.20-3.89]). Despite the
      short follow-up, 42 patients died due to cardiovascular diseases (38.8%), cancer
      (14.9%), and infections (12.7%). Log-FGF23 levels were independently associated
      with death, HR 1.94, 95% CI 1.24-3.03. Mortality risk increased in FGF23
      subgroups from <100 to >400 RU/mL. In a time-changing covariate analysis, serial
      log-FGF23 levels over the 3 years predicted mortality with a HR of 2.66 (95% CI
      1. 79-3.95). CONCLUSION: In a Canadian Asian population with CKD, FGF23 levels
      obtained at 6-monthly intervals for 3 years predicted ESRD and mortality
      suggesting that it is also a risk marker in Asians.

PMID- 28743128
TI  - Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells
      Against Oxidation by Modulating Nitric Oxide Release and Autophagy.
AB  - BACKGROUND/AIMS: the anti-vascular endothelial growth factors (VEGF), Aflibercept
      and Ranibizumab, are used for the treatment of macular degeneration. Here we
      examined the involvement of nitric oxide (NO), mitochondria function and of
      apoptosis/autophagy in their antioxidant effects in human retinal pigment
      epithelium cells (RPE). METHODS: RPE were exposed to Ranibizumab/Aflibercept in
      the absence or presence of NO synthase (NOS) inhibitor and of autophagy
      activator/blocker, rapamicyn/3-methyladenine. Specific kits were used for cell
      viability, NO and reactive oxygen species detection and mitochondrial membrane
      potential measurement, whereas Western Blot was performed for apoptosis/
      autophagy markers and other kinases detection. RESULTS: In RPE cultured in
      physiological conditions, Aflibercept/Ranibizumab increased NO release in a dose
      and time-dependent way. Opposite results were obtained in RPE pretreated with
      hydrogen peroxide. Moreover, both the anti-VEGF agents were able to prevent the
      fall of cell viability and of mitochondrial membrane potential. Those effects
      were reduced by the NOS inhibitor and 3-methyladenine and were potentiated by
      rapamycin. Finally, Aflibercept and Ranibizumab counteracted the changes of
      apoptosis/autophagy markers, NOS, Phosphatidylinositol-3-Kinase/Protein Kinase B
      and Extracellular signal-regulated kinases 1/2 caused by peroxidation.
      CONCLUSION: Aflibercept and Ranibizumab protect RPE against peroxidation through
      the modulation of NO release, apoptosis and autophagy.

PMID- 28743130
TI  - SGLT-2 Inhibition: A Potential New Treatment for Diabetic Kidney Disease?
AB  - Diabetic nephropathy is the leading cause of kidney failure. Treatments with
      drugs that block the renin-angiotensin system have proven beneficial in slowing
      kidney disease progression among those with diabetes; their benefit is limited
      and they do not stop disease progression. Despite multiple clinical trials of
      various interventions including dual blockade of the renin-angiotensin system
      over the past 15 years, no new therapies have emerged to slow kidney disease
      progression in diabetes. SGLT-2 inhibitors are a new class of antiglycemic drugs
      that have been shown to lower blood glucose by inhibition of the sodium-glucose
      transporter 2 in the proximal tubule of the kidney. Several of these inhibitors
      have been marketed for treatment of hyperglycemia in patients with type 2
      diabetes mellitus. In a recent double-blind randomized and placebo-controlled
      trial of cardiovascular outcomes, an SGLT-2 inhibitor-based intervention using
      empagliflozin was shown to be superior to placebo-based regimen for reducing the
      risk of major cardiovascular events among people with type 2 diabetes and
      established cardiovascular disease. In a pre-specified secondary analysis of
      renal outcomes from this trial, Wanner et al. [N Engl J Med 2016;375:323-334]
      recently reported that empagliflozin administration was also associated with
      significant reductions in the progression of kidney disease including the rate of
      decline in estimated glomerular filtration rate (eGFR), progression of
      albuminuria and initiation of renal replacement therapy. While the results of
      this trial are striking and impressive, the majority of those enrolled in the
      trial did not have evidence of diabetic kidney disease as assessed by eGFR or
      albuminuria. Thus, whether or not they represent a breakthrough in the treatment
      of diabetic nephropathy remains to be determined. Several ongoing clinical trials
      are in the planning stages to evaluate SGLT-2 inhibition in a population of
      patients with overt kidney disease. These trials will help to substantiate, or
      not, the potential for this class of drugs to be added to the armamentarium of
      therapeutic strategies to prevent progression of kidney disease in diabetes.

PMID- 28743131
TI  - The Spatial Extent of Epiretinal Electrical Stimulation in the Healthy Mouse
      Retina.
AB  - BACKGROUND/AIMS: Retinal prostheses use electrical stimulation to restore
      functional vision to patients blinded by retinitis pigmentosa. A key detail is
      the spatial pattern of ganglion cells activated by stimulation. Therefore, we
      characterized the spatial extent of network-mediated electrical activation of
      retinal ganglion cells (RGCs) in the epiretinal monopolar electrode
      configuration. METHODS: Healthy mouse RGC activities were recorded with a micro
      electrode array (MEA). The stimuli consisted of monophasic rectangular cathodic
      voltage pulses and cycling full-field light flashes. RESULTS: Voltage tuning
      curves exhibited significant hysteresis, reflecting adaptation to electrical
      stimulation on the time scale of seconds. Responses decreased from 0 to 300 um,
      and were also dependent on the strength of stimulation. Applying the Rayleigh
      criterion to the half-width at half-maximum of the electrical point spread
      function suggests a visual acuity limit of no better than 20/946. Threshold
      voltage showed only a modest increase across these distances. CONCLUSION: The
      existence of significant hysteresis requires that future investigations of
      electrical retinal stimulation control for such long-memory adaptation. The
      spread of electrical activation beyond 200 um suggests that neighbouring
      electrodes in epiretinal implants based on indirect stimulation of RGCs may be
      indiscriminable at interelectrode spacings as large as 400 um.

PMID- 28743132
TI  - Therapeutic Outcomes of Endoscopic Resection of Early Gastric Cancer with
      Undifferentiated-Type Histology: A Korean ESD Registry Database Analysis.
AB  - BACKGROUND/AIMS: To assess the therapeutic outcomes of endoscopic resection (ER)
      of early gastric cancer (EGC) with undifferentiated-type histology. METHODS:
      Cases of ER of EGC with undifferentiated-type histology in the Korean endoscopic
      submucosal dissection (ESD) registry database were identified and reviewed. The
      immediate outcomes, including en bloc resection, complete resection, and curative
      resection rates, and long-term outcomes, including recurrence and survival rates,
      were extracted and analyzed. RESULTS: From 2006 to 2015, 275 EGCs with
      undifferentiated-type histology from 275 patients were identified. The immediate
      outcomes were as follows: en bloc resection rate: 92.4%; complete resection rate:
      80%; and curative resection rate: 36.4%. Compared to patients with lesions that
      were beyond the expanded indication, those with expanded indication lesions
      showed better therapeutic outcomes. There was no difference in immediate outcomes
      between patients with poorly differentiated adenocarcinoma (PDC) and signet ring
      cell carcinoma (SRC). However, compared to ER of SRC, ER of PDC had a stronger
      association with submucosal invasion (41.9% vs. 23.6%, p=0.003). With regard to
      long-term outcomes, there was no difference between lesions with curative and non
      curative resections in the recurrence and mortality rates. These rates also did
      not differ between PDC and SRC (median follow up: 3.96 years). CONCLUSIONS: ER
      confined to expanded indication lesions can be considered for treatment of EGC
      with undifferentiated-type histology.

PMID- 28743133
TI  - Lymphocytic Hypophysitis Successfully Treated with Stereotactic Radiosurgery:
      Case Report and Review of the Literature.
AB  - Lymphocytic hypophysitis (LH) is an autoimmune inflammatory infiltration of the
      pituitary gland, usually with a benign evolution. In rare circumstances the
      inflammatory process may extend beyond the pituitary and infiltrate the
      surrounding structures. We present a 42-year-old woman affected by an aggressive
      form of LH with extension to the cavernous sinus causing internal carotid artery
      occlusion and right sixth cranial nerve palsy. Prednisone therapy caused severe
      iatrogenic Cushing's syndrome, and the patient underwent transsphenoidal
      decompression. The histopathology report was consistent with LH. The patient was
      symptom free for a short period with reappearance of severe headache, diplopia,
      and hearing loss (middle ear inflammation) 3 months after surgery.
      Corticosteroids were reintroduced with the addition of azathioprine, but there
      was no regression of the pituitary mass. The patient was referred for
      stereotactic radiosurgery (SRS) using Gamma Knife (15 Gy to the margin). After 26
      months, azathioprine was stopped, and the dose of prednisone was gradually
      tapered to 7.5 mg/day. Sellar magnetic resonance imaging showed regression of the
      pituitary mass. After follow-up for > 3 years after SRS, there was no clinical or
      radiologic evidence of the disease, but carotid arteries remained occluded. The
      patient developed secondary hypothyroidism and hypogonadism as consequences of
      SRS. An aggressive form of LH extending beyond the pituitary gland infiltrating
      surrounding structures is described. It was successfully treated with SRS after
      failure of transsphenoidal surgery and combined immunosuppressive therapy
      (prednisone, azathioprine). The review of the literature presents timely
      information concerning treatment with azathioprine and SRS of patients with an
      aggressive form of LH.

PMID- 28743134
TI  - Aneurysms of the Intracranial Segment of the Ophthalmic Artery Trunk: Case Report
      and Systematic Literature Review.
AB  - Aneurysms arising from the ophthalmic artery trunk (OAT) are very rare,
      particularly in the artery's intracranial course. The onset of a subarachnoid
      hemorrhage (SAH) from a ruptured OAT aneurysm in this segment is extremely rare.
      We present a case and discuss the anatomy, clinical significance, and therapeutic
      options for an aneurysm at this site. We also retrospectively analyzed the record
      of a patient with a ruptured aneurysm of the intracranial segment of the OAT and
      conducted a comprehensive and systematic review of the PubMed and Scopus
      databases for literature on this pathology. Only one case report of SAH from an
      aneurysm of the intracranial segment of the OAT was published in the literature.
      Only in our case was the intracranial OAT segment aneurysm discovered in the
      acute phase of SAH. Conventional angiography with three-dimensional acquisition
      may help detect aneurysms at this level. Detailed knowledge of the anatomy of the
      OAT is of paramount importance for both surgical and endovascular approaches.
      Surgical treatment is complex because of difficulties in accessing the orbital
      region and the risk of optic nerve and vascular injuries. Endovascular treatment,
      when feasible, could be a good alternative to reduce the risk of loss of vision
      related to surgical manipulation.

PMID- 28743135
TI  - Microsurgical and Endovascular Treatments for Ruptured Paraclinoid Aneurysms.
AB  - BACKGROUND:  The treatment of paraclinoid aneurysms can be challenging due to
      their relationship to the cavernous sinus, carotid siphon, and optic nerve. The
      goal of this retrospective analysis is to compare the efficacy and safety of
      microsurgical versus endovascular treatments for ruptured paraclinoid aneurysms.
      METHODS:  Medical records were reviewed to collect information about patient
      demographics, risk factors, diagnosis (the position and size of aneurysms), Hunt
      and Hess grade, and surgical method and outcomes, including modified Rankin Scale
      (mRS) at the time of discharge and 6 months later, complications, and death.
      RESULTS:  In total, 15 and 6 patients were recruited into the microsurgery and
      endovascular groups, respectively. No difference was detected regarding age, sex,
      risk factors, and Hunt and Hess grade. Most patients had ophthalmic segment
      aneurysms (87% versus 83%; p = 1.000) and small aneurysms (< 10 mm, 67% versus
      100%; p = 0.102). In the microsurgical group, five patients (33%) had large
      aneurysms (10-25 mm); three patients (20%) had multiple aneurysms (all p > 0.05
      compared with the endovascular group). The occlusion rate at 6 months was 93% in
      the microsurgical group and 100% in the endovascular group (p > 0.05). No
      difference was found regarding mRS or the complication and mortality rates
      between the two groups (all p > 0.05). The occurrence of complications was not
      related to the location and size of aneurysms (all p > 0.05). CONCLUSIONS:  Our
      retrospective analysis indicates that good clinical outcomes can be achieved with
      both microsurgical and endovascular approaches. But further prospective
      randomized multicenter studies are needed to provide more evidence for clinical
      practice.

PMID- 28743136
TI  - [Editorial Quality Management in Ophthalmology: Success Factor or Big Effort].

PMID- 28743137
TI  - [Surgical Methods in the Treatment of Uveal Melanoma].
AB  - Significant advancements have been made in the last decades in the treatment of
      uveal melanoma. Radiation therapy can achieve, depending on the method, local
      tumour control in up to 98% of cases. Surgical modalities have been implemented
      in the ocular therapy for uveal melanoma either to treat/prevent radiation
      complications, such as so-called toxic tumour syndrome, or to primarily treat the
      tumour with or without adjunctive radiotherapy. These include endoresection and
      transscleral resection for melanomas of the choroid/ciliary body or irido
      trabeculo-cyclectomy for melanomas of the iris-ciliary body. Furthermore, tumour
      biopsy is playing a progressively more important role in the diagnosis, treatment
      and follow-up planning of melanoma cases. This paper focuses on the background,
      the surgical technique as well as the results and complications of tumour
      excisional and biopsy surgery.

PMID- 28743138
TI  - [ISO 9001:2015 Certification in Quality Management].
AB  - Quality management improves the structures, processes and results of
      organizations of all kinds. Many practices and clinics have their existing
      quality management system certified according to ISO 9001, (e.g., to check their
      own quality management system or to obtain a testimonial against third parties).
      The latest version ISO 9001:2015 contains some changes, both structurally and in
      terms of content. These changes can be met with reasonable efforts. An ISO
      9001:2015 certification represents a value for your organization, but these
      advantages are often not directly measurable.

PMID- 28743139
TI  - Isolated Group of Failures without Denominator.

PMID- 28743140
TI  - A Comparison of Rollback Ratio between Bicruciate Substituting Total Knee
      Arthroplasty and Oxford Unicompartmental Knee Arthroplasty.
AB  - The purpose of this study was to compare the rollback ratio in bicruciate
      substituting (BCS) total knee arthroplasty (TKA) and bicruciate-retaining Oxford
      unicompartmental knee arthroplasty (UKA). In this study, 64 subjects (64 knees)
      undergoing BCS-TKA (Journey II: Smith and Nephew) and 50 subjects (50 knees)
      undergoing Oxford UKA (Zimmer-Biomet holdings, Inc., IN) were included.
      Approximately 6 months after surgery, and when the subjects had recovered their
      knee range of motion, following the Laidlow's method, lateral radiographic
      imaging of the knee was performed with active full knee flexion. The most
      posterior tibiofemoral contact point was measured for the evaluation of femoral
      rollback (rollback ratio). Flexion angle was also measured using the same
      radiograph and the correlation of rollback and flexion angle was analyzed. As a
      control, radiographs of the asymptomatic contralateral knees of subjects
      undergoing Oxford UKA were evaluated (50 knees). The rollback ratios of the BCS
      TKA, Oxford UKA, and control knees were 37.9 +/- 4.9, 35.7 +/- 4.2, and 35.3 +/-
      4.8% respectively. No significant difference in rollback ratio was observed among
      the three groups. The flexion angles of the BCS-TKA, Oxford UKA, and control
      knees were 123.8 +/- 8.4, 125.4 +/- 7.5, and 127 +/- 10.3 degrees, respectively.
      No significant difference in knee flexion angle was observed among the three
      groups. Significant correlation between rollback ratio and knee flexion angle was
      observed (p = 0.002; Pearson's correlation coefficient = - 0.384). BCS-TKA showed
      no significant difference in rollback ratio when compared with control knees and
      Oxford UKA knees. The BCS-TKA design is likely to reproduce native anterior
      cruciate ligament and posterior cruciate ligament function, and native knee
      rollback.

PMID- 28743141
TI  - Variations in Tibial Tuberosity to Trochlear Groove and Posterior Cruciate
      Ligament Distances due to Tibial External and Valgus Rotations.
AB  - Tibial rotations with respect to the femur influence measurements used to assess
      the lateral position of the tibial tuberosity. This study utilized computational
      modeling to quantify how the tibial tuberosity to trochlear groove (TT-TG) and
      tibial tuberosity to posterior cruciate ligament attachment (TT-PCL) distances
      vary with tibial internal/external and varus/valgus rotations. Computational
      models were developed from magnetic resonance imaging data to represent eight
      knees with patellar instability. TT-TG and TT-PCL distances were quantified from
      the computational models for a neutral orientation and with the tibia rotated
      internally and externally and into varus and valgus in 1-degree increments to 5
      degrees. Regression analyses related tibial rotations to TT-TG and TT-PCL
      distances. TT-TG distance increased with tibial external rotation, and both TT-TG
      and TT-PCL distances increased with valgus orientation (r2 > 0.94 for all
      regressions). The average increase in TT-TG distance for each 1 degree of tibial
      external rotation was 0.55 mm (range: 0.50-0.62 mm), compared with 0.00 mm
      (range: -0.05 to 0.04 mm) for TT-PCL distance. The average increase in TT-TG
      distance for each 1 degree of valgus was 1.01 mm (range: 0.91-1.14 mm), compared
      with 0.46 mm (range: 0.32-0.60 mm) for TT-PCL distance. TT-TG distance varies
      more with tibial rotations than TT-PCL distance due to both points being on the
      tibia and a smaller proximal-distal distance between the points for TT-PCL
      distance.

PMID- 28743142
TI  - Infrapatellar Fat Pad Impingement: A Systematic Review.

PMID- 28743143
TI  - Pitfalls in Diagnosis of Early-Onset Inflammatory Bowel Disease.
AB  - AIM:  The onset of inflammatory bowel disease (IBD) in patients younger than the
      age of 5 years is rare. Moreover, when there is exclusive colonic inflammation,
      diagnosis can be challenging. Our aim was to describe the difficulties and
      pitfalls in the diagnosis of early-onset IBD (eoIBD) and their repercussions in
      treatment decisions. PATIENTS AND METHODS:  Patients with eoIBD (Crohn's disease
      [CD], ulcerative, and unclassified colitis) treated at our center between 1990
      and 2016 were studied retrospectively. Demographic, clinical, medical, and
      surgical treatment data were analyzed. RESULTS:  A total of 19 patients were
      diagnosed with eoIBD at 21 (1-46) months of age. Bloody diarrhea, growth failure,
      and abdominal pain were present in 90, 42, and 16%, respectively. After 9 (1-62)
      months from the onset, patients were classified as ulcerative colitis (nine), CD
      (two), and unclassified colitis (eight). Unresponsiveness to medical treatment
      was observed in 10 and prompted surgical assessment. A partial colectomy was
      performed in one, and nine underwent a total colectomy (one end stoma and eight
      ileoanal anastomosis [IAA]). At least one surgical complication occurred in 80%
      and ultimately six patients with an IAA required an end stoma. Overtime, final
      diagnosis of 5 out of the 10 surgical patients changed due to biopsy findings,
      unresponsiveness to medical treatment, or extraintestinal and perianal
      manifestations. After a 12-year (1-22) follow-up, 57.9% of the diagnoses of all
      patients were modified. CONCLUSION:  EoIBD poses a challenge due to ambiguous
      presentation and absence of specific diagnostic tests. Surgical evaluation is
      often needed and surgeons must be mindful of possible initial misdiagnosis, in
      addition to short- and long-term outcomes before deciding aggressive surgical
      measures as well as intestinal reconstruction.

PMID- 28743144
TI  - Appendiceal Intussusception: A Diagnostic Challenge.
AB  - INTRODUCTION:  Appendiceal intussusception is a rare condition in children
      characterized by an invagination of the appendix into the cecum to various
      degrees. The treatment is appendectomy; however since symptoms are not specific,
      clinical diagnosis is challenging and frequently only intraoperative. We present
      a series of five patients with appendiceal intussusception and discuss features
      that may direct the pediatric surgeon to achieve early recognition and provide
      optimal treatment. MATERIALS AND METHODS:  The database of a tertiary medical
      center was retrospectively reviewed for all patients treated for appendiceal
      intussusception during the period from January 1995 to January 2016. Data
      collected by chart review included demographics, clinical characteristics,
      imaging studies, surgical technique, and outcome. The findings were analyzed by
      descriptive statistics. RESULTS:  This series included five patients (two females
      and three males) with ages ranging between 27 and 42 months (mean: 35.2).
      Patients presented with intermittent abdominal pain (IAP, all five patients),
      alternate vomiting (three of five patients), alternate diarrhea (two of five
      patients), fever (two of five patients), and rectal bleeding (one of five
      patients). The average length of symptoms was 22.6 days. Eighteen diagnostic
      studies were performed, including abdominal ultrasound for all patients, barium
      enema for three patients with secondary ileocolic intussusception, and abdominal
      computed tomography (CT) for one patient. The average number of studies per
      patient was 3.6. In surgery, the appendiceal intussusception was found to be
      complete in four patients, whereas it was partial in the remaining patient. In
      all patients, appendectomy was performed with resection of a small rim of cecal
      wall due to marked congestion and edema in an attempt to decrease recurrence.
      CONCLUSION:  The mainstay of clinical presentation is intermittent abdominal pain
      while patients may be completely asymptomatic between attacks. Appendiceal
      intussusception may act as a leading point to ileocolic intussusception and is
      frequently concealed by it. The treatment is appendectomy. Both pediatric
      surgeons and radiologists should be aware of this occurrence to provide adequate
      management and avoid complications.

PMID- 28743145
TI  - Endoscopic submucosal dissection of early colorectal neoplasms with a monopolar
      scissor-type knife: short- to long-term outcomes.
AB  - Background and study aims Endoscopic submucosal dissection (ESD) for colorectal
      neoplasms remains challenging because of technical issues imposed by the complex
      anatomical features of the large intestine. We evaluated the feasibility, and the
      short- and long-term clinical outcomes of ESD for early colorectal neoplasms
      performed using the Stag-beetle Knife Jr. (SB Knife Jr.) Patients and methods We
      retrospectively assessed 228 patients who underwent ESD for 247 colorectal
      lesions with the SB Knife Jr. Clinicopathological characteristics of the
      neoplasms, complications, and various short- and long-term outcomes were
      evaluated. Results Mean tumor size was 34.3 mm and median procedure time was 76
      minutes. The SB Knife Jr. achieved 98.4 % en bloc resection, 93.9 % complete
      resection, and 85.4 % curative resection. No perforations occurred during the
      procedure, and a delayed bleeding rate of 2.4 % was observed. Long-term outcomes
      were favorable with no distant recurrence, 1.1 % local recurrence, a 5-year
      overall survival rate of 94.1 % and 5-year tumor-specific survival rate of 98.6 %
      in patients with cancer. Conclusions ESD using the SB Knife Jr. is technically
      efficient and safe in treating early colorectal neoplasms and is associated with
      favorable short- and long-term outcomes.

PMID- 28743146
TI  - ?

PMID- 28743147
TI  - [Development of Anaesthesia-Related Mortality and Impact On Perioperative
      Outcome].
AB  - Achievements in anaesthesiology form the basis for the tremendous development of
      surgical therapy. Reliable monitoring technology, which is scrutinized on a
      regular basis using checklists, is allowing anaesthesia at the borders of
      physiology. During the last decades, anaesthesia-related mortality has been
      decreasing considerably. Well-trained anaesthesiology staff, who considers
      patient- and procedure-specific risks in anaesthetic management, is of major
      importance. Furthermore, postoperative care in specialised units and intensive
      care wards is a key factor of improved patient outcome after surgery. In the
      future, unravelling the interactions of anaesthesia, surgical trauma and
      postoperative complications will further contribute to improved patient safety.

PMID- 28743148
TI  - [Impact of Cardiac Anaesthesia on Patient Outcome].
AB  - The perioperative management of complex patients in a highly technical and
      subspecialized environment is the domain of the cardiac anesthesiologist.
      Evidence suggests that hemodynamic management using goal directed hemodynamic
      therapy (GDHT) improves patient outcome. Organ protection remains a main concern
      during cardiac surgery using extracorporeal circulation. Mortality can be
      decreased when remote ischemic preconditioning techniques (RIPC) are being used.
      Neurological outcomes can be improved with near-infrared-spectometry (NIRS),
      volatile anesthetics increase myocardial protection through preconditioning and
      perioperative echocardiography increases overall patient survival.

PMID- 28743149
TI  - [The Influence of Anesthesia On Perioperative Outcome in Children - Institutional
      and Individual Factors].
AB  - The perioperative care of children is challenging for health care providers.
      Since anesthetists cannot affect the nature of the disease and have hardly an
      impact on the decision for surgery we summarized in this review individual and
      institutional factors for improving perioperative outcome by anesthetists.
      Individual factors include the level of education and the professional experience
      of the anesthetist as well as an anesthetic management that is focused on the
      maintenance of an adequate cerebral perfusion. Besides individual factors this
      review emphasizes the importance of institutional factors as measures to reduce
      anxiety and insecurity of the parents which result in less distress and coping of
      the children in the postanesthesia care unit as well as less need for pain
      medication, less emergence delirium and less sleep disorders. A behaviorally
      oriented preoperative preparation of parents and children also affects the
      postoperative course of the pediatric patients positively as well as
      institutional concepts for the reduction of perioperative medication errors and
      adverse drug events. We believe that perspectively pediatric surgery will be
      increasingly performed in high volume hospitals which are able to guarantee
      beneficial institutional structures as well as a high educational level and high
      professional experience of the employed anesthetists.

PMID- 28743150
TI  - [Anesthesiology and Outcome - Impact of the Perioperative Process].
AB  - In recent years, the role of the anesthesiologist has turned tremendously from
      the "anaesthesia doctor" into a perioperative physician and risk specialist.
      Patients are older, multimorbid, and are called up for more and more extensive
      surgery and interventions. Socioeconomic aspects have grown in importance. The
      anesthesiologist, paving the way for a good outcome, is involved in nearly all
      perioperative processes: preoperative evaluation, definition and optimization of
      preoperative and intraoperative conditions, management of modern intraoperative
      anesthesia as well as postoperative medically indicated, effective and efficient
      treatment of partially highly complex patients. The individual perioperative
      process steps in this way are examined in accordance with established guidelines
      and the increase in current requirements. Finally, a special emphasis is placed
      on the perception that the perioperative process has not been completed with the
      end of surgery - postoperative outcome is not least adversely affected by
      postoperative complications on the normal ward. The risk of death after
      complications, "failure to rescue", should be identified early and treated
      promptly.

PMID- 28743151
TI  - [Remifentanil Up2date - Part 1].
AB  - Remifentanil is a short-acting opioid of high analgetic potency and superior
      controllability. It is widely used in day-case surgery, procedural sedation, for
      reduction of recovery-times and obstetrics and whenever excellent controllability
      of opioid effects is needed. Especially in combination with Propofol it is used
      for target-controlled infusion (TCI). The first part of the article provides
      readers with information about historical aspects, pharmacological
      characteristics, effects and side effects of remifentanil.

PMID- 28743152
TI  - [Prevention of Perioperative Hypothermia - Guidelines for Daily Clinical
      Practice].
AB  - Inadvertent perioperative hypothermia (body core temperature < 36  degrees C) is
      a serious complication leading to increased rates of wound infection, higher
      blood loss associated with increased transfusion requirements as well as patient
      dissatisfaction among others. Body core temperature is a vital parameter and
      needs constant monitoring just like heart rate, blood pressure and arterial
      oxygen saturation. Patient-, anesthesia-, surgery- and environment-related risk
      factors were identified for occurring perioperative hypothermia.The avoidance of
      perioperative hypothermia requires a multidisciplinary approach for both medical
      and assistant staff. A bundle of procedures has to be arranged in order to
      improve patient outcome. Steps include general (e.g. staff instruction), pre-
      (e.g. prewarming), intra- (e.g. active warming) and postoperative (e.g. drug
      therapy) actions. An effective concept for prevention of perioperative
      hypothermia has to be adjusted to departments' specific constructional,
      organizational, process-related and staff characteristics with clearly visible
      and assigned responsibilities.

PMID- 28743153
TI  - [How Much Alarm Can the Human Being Tolerate?]
AB  - Due to growing technisation of intensive care the number of devices with
      integrated alarm systems is steadily increasing. However, most of the sounding
      alarms are false alarms causing high levels of frustration, aggression and
      inappropriate behaviour amongst the medical personnel. All this jeopardises
      patient care. The high number of alarms also disturb the patients interrupting
      their sleep and provokes anxiety, and also increases the already high noise level
      in intensive care units and the operating theatre alike. In the interest of the
      medical staff and our patients, we should reduce the high frequency of false
      alarms by using modern alarm algorithms techniques, lower both noise exposure and
      stress load with the help of modern individualized alarm systems and by
      increasing awareness on the dangers of alarm fatigue through training and by
      using individualized patient-related alarm limits. Despite economic challenges
      hospitals and intensive care units should optimize staffing, thereby lowering the
      risk to patients and improving employee satisfaction.

PMID- 28743154
TI  - [Generation Y: the Uncertain Future of Surgery].

PMID- 28743155
TI  - Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder
      cancer with variant histology.
AB  - BACKGROUND: Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a
      significant survival benefit. However, to the authors' knowledge, it is unknown
      whether this benefit persists in histological variants. The objective of the
      current study was to assess the effect of neoadjuvant chemotherapy on the
      probability of non-organ-confined disease and overall survival after radical
      cystectomy (RC) in patients with histological variants. METHODS: Querying the
      National Cancer Data Base, the authors identified 2018 patients with histological
      variants who were undergoing RC for bladder cancer between 2003 and 2012.
      Variants were categorized as micropapillary or sarcomatoid differentiation,
      squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other
      histology. Logistic regression models estimated the odds of non-organ-confined
      disease at the time of RC for each histological variant, stratified by the
      receipt of neoadjuvant chemotherapy. Cox regression models were used to examine
      the effect of neoadjuvant chemotherapy on overall mortality in each variant
      subgroup. RESULTS: Patients with neuroendocrine tumors (odds ratio [OR], 0.16;
      95% confidence interval [95% CI], 0.08-0.32 [P<.001]), micropapillary
      differentiation (OR, 0.30; 95% CI, 0.10-0.95 [P=.041]), sarcomatoid urothelial
      carcinoma (OR, 0.40; 95% CI, 0.17-0.94 [P=.035]), and adenocarcinoma (OR, 0.24;
      95% CI, 0.06-0.91 [P=.035]) were less likely to harbor non-organ-confined disease
      at the time of RC when treated with neoadjuvant chemotherapy. An overall survival
      benefit for neoadjuvant chemotherapy was only found in patients with
      neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]).
      CONCLUSIONS: Patients with neuroendocrine tumors benefit from neoadjuvant
      chemotherapy, as evidenced by better overall survival and lower rates of non
      organ-confined disease at the time of RC. For tumors with micropapillary
      differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant
      chemotherapy decreased the frequency of non-organ-confined disease at the time of
      RC. However, this favorable effect did not translate into a statistically
      significant overall survival benefit for these patients, potentially due to the
      aggressive tumor biology. Cancer 2017;123:4346-55. (c) 2017 American Cancer
      Society.

PMID- 28743156
TI  - Components of mesophyll resistance and their environmental responses: A
      theoretical modelling analysis.
AB  - Mesophyll resistance (rm ), stomatal resistance, and biochemical limitations are
      recognized as three critical factors limiting leaf photosynthesis. Contrary to
      the expectation of being a constant, rm not only varies with light and CO2
      conditions but also shows different responses among species. To elucidate the
      mechanistic basis of these responses, we derived an analytical model of rm ,
      which incorporates various anatomical and biochemical factors including
      permeabilities of cell wall and chloroplast envelope to CO2 and HCO3- , carbonic
      anhydrase activities in cytosol and stroma, Rubisco activities, and relative
      location of mitochondria and chloroplast. The robustness of this model was
      confirmed by comparing the predicted rm and its components to numerical models
      developed at cell and leaf levels, which incorporate detailed 3-dimensional cell
      and leaf anatomies, CO2 hydration and diffusion processes from intercellular air
      space to stroma, and CO2 fixation by Rubisco. A combination of these model
      analyses shows that the varying rm is influenced by four biochemical factors: (a)
      nonuniform photosynthesis status across the leaf, (b) photorespiration and
      respiration, (c) bicarbonate leakage on the chloroplast envelope, and (d)
      hydration activity in cytosol and stroma. This study provides a theoretical
      framework to study components of rm and their responses to environmental
      perturbations.

PMID- 28743157
TI  - HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation
      Consortium.
AB  - BACKGROUND: Human epidermal growth factor receptor 2 (HER2) mutations have been
      reported in lung adenocarcinomas. Herein, the authors describe the prevalence,
      clinical features, and outcomes associated with HER2 mutations in 1007 patients
      in the Lung Cancer Mutation Consortium (LCMC). METHODS: Patients with advanced
      stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were
      assessed for diagnosis and adequacy; multiplexed genotyping was performed in
      Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories to
      examine 10 oncogenic drivers. The LCMC database was queried for patients with
      HER2 mutations to access demographic data, treatment history, and vital status.
      An exploratory analysis was performed to evaluate the survival of patients with
      HER2 mutations who were treated with HER2-directed therapies. RESULTS: A total of
      920 patients were tested for HER2 mutations; 24 patients (3%) harbored exon 20
      insertion mutations (95% confidence interval, 2%-4%). One patient had a
      concurrent mesenchymal-epithelial transition factor (MET) amplification. The
      median age of the patients was 62 years, with a slight predominance of females
      over males (14 females vs 10 males). The majority of the patients were never
      smokers (71%) and presented with advanced disease at the time of diagnosis. The
      median survival for patients who received HER2-targeted therapies (12 patients)
      was 2.1 years compared with 1.4 years for those who did not (12 patients) (P =
      .48). Patients with HER2 mutations were found to have inferior survival compared
      with the rest of the LCMC cohort with other mutations: the median survival was
      3.5 years in the LCMC population receiving targeted therapy and 2.4 years for
      patients not receiving targeted therapy. CONCLUSIONS: HER2 mutations were
      detected in 3% of patients with lung adenocarcinoma in the LCMC. HER2-directed
      therapies should be investigated in this subgroup of patients. Cancer
      2017;123:4099-4105. (c) 2017 American Cancer Society.

PMID- 28743158
TI  - Thrombus formation 4 years after percutaneous transcatheter closure of an atrial
      septal defect.

PMID- 28743159
TI  - Chronic hepatitis C virus infection and neurocognitive function in adult
      survivors of childhood cancer.
AB  - BACKGROUND: Cancer survivors transfused with blood products before reliable
      screening for hepatitis C virus (HCV) are at risk for infection. This study
      examined the impact of HCV on neurocognitive function and health-related quality
      of life (HRQOL) among adult survivors of childhood cancer. METHODS:
      Neurocognitive testing was conducted for 836 adult survivors of childhood cancer
      (mean age, 35 years [standard deviation, 7.4 years]; time since diagnosis, 29
      years [standard deviation, 6.2 years]) who received blood products before
      universal HCV screening. No differences were observed between confirmed HCV
      seropositive survivors (n = 79) and HCV-seronegative survivors (n = 757) in the
      primary diagnosis or neurotoxic therapies. Multivariate regression models were
      used to compare functional outcomes between seropositive and seronegative
      survivors. RESULTS: Compared with seronegative survivors, seropositive survivors
      demonstrated lower performance on measures of attention (P < .001), processing
      speed (P = .008), long-term verbal memory (P = .01), and executive function (P =
      .001). After adjustments for sex, age at diagnosis, and treatment exposures,
      seropositive survivors had a higher prevalence of impairment in processing speed
      (prevalence ratio [PR], 1.3; 95% confidence interval [CI], 1.1-1.6) and executive
      functioning (PR, 1.3; 95% CI, 1.1-1.6). Differences were not associated with the
      treatment of HCV or the presence of liver cirrhosis. Seropositive survivors
      reported worse general HRQOL (PR, 1.6; 95% CI, 1.2-2.1), which was associated
      with the presence of liver cirrhosis (P = .001). CONCLUSIONS: Survivors of
      childhood cancer with a history of HCV infection are at risk for neurocognitive
      impairment and reduced HRQOL beyond the known risks associated with neurotoxic
      cancer therapies. Cancer 2017;123:4498-505. (c) 2017 American Cancer Society.

PMID- 28743160
TI  - The prognostic utility of baseline alpha-fetoprotein for hepatocellular carcinoma
      patients.
AB  - INTRODUCTION: Alpha-fetoprotein (AFP) has a valuable role in postoperative
      surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of
      pretreatment or baseline AFP remains controversial. The present study
      hypothesized that elevated baseline AFP levels are associated with worse overall
      survival in HCC patients. METHODS: Adult HCC patients were identified using the
      National Cancer Database (2004-2013). Patients were stratified according to
      baseline AFP measurements into the following groups: Negative (<20), Borderline
      (20-199), Elevated (200-1999), and Highly Elevated (>2000). The primary outcome
      was overall survival (OS), which was analyzed by log-rank test and graphed using
      Kaplan-Meier method. Multivariate regression modeling was used to determine
      hazard ratios (HR) for OS. RESULTS: Of 41 107 patients identified, 15 809 (33.6%)
      were Negative. Median overall survival was highest in the Negative group,
      followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2
      months; P < 0.001). On multivariate analysis, overall survival hazard ratios for
      the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94
      (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative). CONCLUSION:
      Baseline AFP independently predicted overall survival in HCC patients regardless
      of treatment plan. A baseline AFP value is a simple and effective method to
      assist in expected survival for HCC patients.

PMID- 28743161
TI  - Reply.

PMID- 28743162
TI  - Contemporary use trends and survival outcomes in patients undergoing radical
      cystectomy or bladder-preservation therapy for muscle-invasive bladder cancer.
AB  - BACKGROUND: The current study was performed to examine temporal trends and
      compare overall survival (OS) in patients undergoing radical cystectomy (RC) or
      bladder-preservation therapy (BPT) for muscle-invasive urothelial carcinoma of
      the bladder. METHODS: The authors reviewed the National Cancer Data Base to
      identify patients with AJCC stage II to III urothelial carcinoma of the bladder
      from 2004 through 2013. Patients receiving BPT were stratified as having received
      any external-beam radiotherapy (any XRT), definitive XRT (50-80 grays), and
      definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the
      BPT and RC cohorts were evaluated using Cochran-Armitage tests, unadjusted Kaplan
      Meier curves, adjusted Cox multivariate regression, and propensity score
      matching, using increasingly stringent selection criteria. RESULTS: A total of
      32,300 patients met the inclusion criteria and were treated with RC (22,680
      patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540
      patients) and 15.5% (1489 patients), respectively, were treated with definitive
      XRT and CRT. Improved OS was observed for RC in all groups. After adjustments
      with more rigorous statistical models controlling for confounders and with more
      restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on
      multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95%
      CI], 2.045-2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773-1.972]; and CRT: HR,
      1.578 [95% CI, 1.474-1.691]) and propensity score (any XRT: HR, 2.008 [95% CI,
      1.871-2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453-1.776]; and CRT: HR, 1.406
      [95% CI, 1.235-1.601]) analyses. CONCLUSIONS: In the National Cancer Data Base,
      receipt of BPT was associated with decreased OS compared with RC in patients with
      stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT
      and more rigorous statistical methods adjusting for selection biases attenuated
      observed survival differences. Cancer 2017;123:4337-45. (c) 2017 American Cancer
      Society.

PMID- 28743163
TI  - ALK and ROS1 testing on lung cancer cytologic samples: Perspectives.
AB  - Cytologic sampling is the mainstay of diagnosing advanced lung cancer. Moreover,
      to select patients for personalized first-line or second-line treatment,
      epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase
      (ALK) and c-ros oncogene 1 (ROS1) rearrangements are tested on cytologic
      preparations. Commercially available fluorescence in situ hybridization (FISH)
      and immunocytochemistry (ICC) assays have primarily been used for the
      identification of cells harboring ALK or ROS1 gene fusions on histologic rather
      than cytologic preparations. However, it is now recognized that FISH and ICC also
      can be applied on cytologic samples provided the cytopathologist is aware that
      FISH and ICC results are not always concordant and that the performance of ICC
      largely depends on antibody clones, signal detection systems, and scoring
      systems. Notably, the routine clinical use of FISH and ICC may be replaced by
      emerging next-generation sequencing and digital, color-coded barcode
      technologies, which have the advantage of simultaneously evaluating ALK, ROS1,
      and EGFR alterations in a single analysis. Although their use in clinical
      cytologic practice remains to be fully established, it is conceivable that this
      technology will replace both FISH and ICC analyses in future diagnostic
      algorithms. Here, the authors review studies devoted to testing ALK and ROS1 on
      cytology specimens in an attempt to provide an update for the cytopathologist
      regarding current and evolving practice. Cancer Cytopathol 2017;125:817-30. (c)
      2017 American Cancer Society.

PMID- 28743164
TI  - Decisions to Attend and Drink at Party Events: The Effects of Incentives and
      Disincentives and Lifetime Alcohol and Antisocial Problems.
AB  - BACKGROUND: Alcohol use disorders are associated with patterns of impulsive/risky
      decision making on behavioral economic decision tasks, but little is known about
      the factors affecting drinking-related decisions. METHODS: The effects of
      incentives and disincentives to attend and drink at hypothetical alcohol-related
      party events as a function of lifetime (LT) alcohol and antisocial problems were
      examined in a sample of 434 young adults who varied widely in LT alcohol and
      antisocial problems. RESULTS: Moderate and high disincentives substantially
      discouraged decisions to attend the party events and were associated with
      decisions to drink less at the party events. High versus low party incentives
      were associated with more attendance decisions. LT antisocial problems were
      associated with being less deterred from attending by moderate and high
      disincentives. LT alcohol problems were associated with greater attendance at
      high party incentive contexts. LT alcohol problems were associated with drinking
      more at the majority of events; however, the results indicate that young adults
      with high levels of alcohol problems moderate their drinking in response to
      moderate and high disincentives. Finally, attendance and drinking decisions on
      this hypothetical task were significantly related to actual drinking practices.
      CONCLUSIONS: The results suggest that antisocial symptoms are associated with a
      reduced sensitivity to the potential negative consequences of drinking, while
      alcohol problems are associated with a greater sensitivity to the rewarding
      aspects of partying. The results also underline the value of directly assessing
      drinking-related decisions in different hypothetical contexts as well as
      assessing decisions about attendance at risky drinking events in addition to
      drinking amount decisions.

PMID- 28743165
TI  - Prognostic factors and survival outcomes in patients with chronic myeloid
      leukemia in blast phase in the tyrosine kinase inhibitor era: Cohort study of 477
      patients.
AB  - BACKGROUND: Outcomes in patients with chronic myeloid leukemia in blast phase
      (CML-BP) are historically dismal. Herein, the authors sought to analyze the
      characteristics, prognostic factors, and survival outcomes in patients with CML
      BP in the tyrosine kinase inhibitor (TKI) era. METHODS: A total of 477 patients
      with CML-BP were treated with a TKI at some point during the course of their CML.
      Cox proportional hazard models identified characteristics that were predictive of
      survival. Overall survival and failure-free survival were assessed. Optimal
      cutoff points for specific parameters were identified using classification and
      regression tree (CART) analysis. RESULTS: The median age of the patients was 53
      years (range, 16-84 years) and 64% were male. Approximately 80% of patients
      initially were diagnosed in the chronic phase of CML at a median of 41 months
      (range, 0.7-298 months) before transformation to CML-BP. De novo CML-BP occurred
      in 71 patients. Approximately 72% of patients received TKI therapy before CML-BP.
      The initial therapy for CML-BP included a TKI alone (35%), a TKI with
      chemotherapy (46%), and non-TKI therapies (19%). The median overall survival was
      12 months and the median failure-free survival was 5 months. In multivariate
      analysis, myeloid immunophenotype, prior TKI, age >=58 years, lactate
      dehydrogenase level >=1227 IU/L, platelet count < 102 K/MUL, no history of stem
      cell transplantation, transition to BP from chronic phase/accelerated phase, and
      the presence of chromosome 15 aberrations predicted for a significantly increased
      risk of death. Achievement of major hematologic response and/or complete
      cytogenetic response to first-line treatment was found to be predictive of better
      survival. The combination of a TKI with intensive chemotherapy followed by stem
      cell transplantation appeared to confer the best outcome. CONCLUSIONS: Patients
      with CML-BP continue to pose a therapeutic challenge, have dismal outcomes, and
      require newer treatment approaches. Cancer 2017;123:4391-402. (c) 2017 American
      Cancer Society.

PMID- 28743166
TI  - Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic
      myeloid leukemia.
AB  - BACKGROUND: Several studies have demonstrated that approximately one-half of
      patients with chronic myeloid leukemia (CML) who receive treatment with tyrosine
      kinase inhibitors (TKIs) and achieve and maintain a deep molecular response (DMR)
      are able to successfully discontinue therapy. In patients who have a molecular
      relapse, a DMR is rapidly regained upon treatment re-initiation. METHODS: The
      authors report the results from RE-STIM, a French observational, multicenter
      study that evaluated treatment-free remission (TFR) in 70 patients who re
      attempted TKI discontinuation after a first unsuccessful attempt. After the
      second TKI discontinuation attempt, the trigger for treatment re-introduction was
      the loss of a major molecular response in all patients. RESULTS: The median
      follow-up was 38.3 months (range, 4.7-117 months), and 45 patients (64.3%) lost a
      major molecular response after a median time off therapy of 5.3 months (range, 2
      42 months). TFR rates at 12, 24, and 36 months were 48% (95% confidence interval
      [CI], 37.6%-61.5%), 42% (95% CI, 31.5%-55.4%), and 35% (95% CI, 24.4%-49.4%),
      respectively. No progression toward advanced-phase CML occurred, and no efficacy
      issue was observed upon TKI re-introduction. In univariate analysis, the speed of
      molecular relapse after the first TKI discontinuation attempt was the only factor
      significantly associated with outcome. The TFR rate at 24 months was 72% (95% CI,
      48.8%-100%) in patients who remained in DMR within the first 3 months after the
      first TKI discontinuation and 36% (95% CI, 25.8%-51.3%) for others. CONCLUSIONS:
      This study is the first to demonstrate that a second TKI discontinuation attempt
      is safe and that a first failed attempt at discontinuing TKI does not preclude a
      second successful attempt. Cancer 2017;123:4403-10. (c) 2017 American Cancer
      Society.

PMID- 28743167
TI  - Preoperative bevacizumab and volumetric recovery after resection of colorectal
      liver metastases.
AB  - BACKGROUND AND OBJECTIVES: While preoperative treatment is frequently
      administered to CRLM patients, the impact of chemotherapy, with or without
      bevacizumab, on liver regeneration remains controversial. METHODS: The early and
      late regeneration indexes were defined as the relative increase in liver volume
      (RLV) within 2 and 9 months from surgery. Regeneration rates of the preoperative
      treatment groups were compared. RESULTS: Preoperative chemotherapy details and
      volumetric data were available for 185 patients; 78 (42.2%) received preoperative
      chemotherapy with bevacizumab (Bev+), 46 (24.8%) received chemotherapy only (Bev
      ), and 61 (33%) received no chemotherapy. Patients in the Bev+ and Bev- groups
      received similar chemotherapy cycles (4 [3-6] vs 4 [4-6]; P = 0.499). Despite the
      comparable clinicopathological characteristics and Resected Volume/Total Liver
      Volume (TLV) at surgery (P = 0.944) of both groups, Bev+ group had higher early
      and late regeneration (17.2% vs 4.3%; P = 0.035 and 14.0% vs 9.4%; P = 0.091,
      respectively). Of note, early and late regeneration rates (3.7% and 10.9% vs 6.6%
      and 5.5%, respectively) were comparable between the no chemotherapy and Bev-
      groups (all P > 0.05). In multivariable analysis -adjusted for gender, age,
      portal vein embolization, preoperative chemotherapy, resected liver volume, tumor
      number, postoperative chemotherapy, fibrosis, steatosis- bevacizumab
      independently predicted early liver regeneration (P = 0.019). CONCLUSION: Our
      findings suggest that preoperative bevacizumab administered along with
      chemotherapy was associated with enhanced volumetric restoration. Interestingly,
      this effect was more pronounced among patients who received oxaliplatin-based
      regimens and bevacizumab compared to those treated with irinotecan-based regimens
      and bevacizumab.

PMID- 28743168
TI  - Calorie restriction reverses age-related alteration of cavernous neurovascular
      structure in the rat.
AB  - Calorie restriction (CR) refers to a reduction of calorie intake without
      compromising essential nutrients to avoid malnutrition. CR has been established
      as a non-genetic method of altering longevity and attenuating biological changes
      associated with aging. Aging is also an important risk factor for erectile
      dysfunction. The aim of this study was to examine whether CR diet can reverse the
      age-related alterations of erectile tissue in the aged rat. Four groups of rats
      were used: young rats (7 months) + ad libitum, aged rats (22 months) + ad
      libitum, young rats + CR diet, and aged rats + CR diet. The ad libitum group had
      free access to both food and water, and CR groups were fed 60% of the food intake
      of their ad libitum littermates, starting from 6 weeks before sacrifice. The
      penis was harvested and stained with antibodies to von Willebrand factor, smooth
      muscle alpha-actin, platelet-derived growth factor receptor-beta, phospho-eNOS,
      nNOS, and neurofilament. We also performed Masson trichrome staining and TUNEL
      assay. The blood samples were collected for the measurement of serum total
      testosterone level. The contents of endothelial cells, smooth muscle cells,
      pericytes, and neuronal cells as well as serum testosterone levels were
      significantly lower in the penis of aged rats than in their young littermates. CR
      significantly restored cavernous endothelial cells, smooth muscle cells,
      pericytes, and neuronal cell contents and decreased cavernous endothelial cell
      apoptosis and fibrosis in both young and aged rats. CR also increased serum
      testosterone level in aged rats, but not in young rats. CR successfully improved
      age-related derangements in penile neurovascular structures and hormonal
      disturbance. Along with a variety of lifestyle modifications, our study gave us a
      scientific rationale for CR as a non-pharmaceutical strategy to reprogram damaged
      erectile tissue toward neurovascular repair in aged men.

PMID- 28743169
TI  - Development and validation of an optical biosensor for rapid monitoring of
      adalimumab in serum of patients with Crohn's disease.
AB  - Therapeutic drug monitoring of adalimumab is recommended to improve therapeutic
      outcome in patients with Crohn's disease. Performing an ELISA requires a rather
      long time-to-result and the necessity of collecting multiple samples to decrease
      the cost per adalimumab determination. In this study, we aim to develop and
      validate a rapid assay suitable for measuring a single adalimumab serum sample
      using a fiber-optic surface plasmon resonance (FO-SPR) based sensor. Therefore,
      we have immobilized MA-ADM28B8 as capture antibody on an FO-probe and conjugated
      MA-ADM40D8 as detecting antibody to gold nanoparticles. A dose-response curve
      ranging from 2.5 to 40 ng/mL adalimumab was obtained in 1/400 diluted serum.
      Serum samples of patients with adalimumab concentrations between 1 and 16 MUg/mL
      were measured whereas the negative control, a sample spiked with infliximab at a
      concentration of 16 MUg/mL, showed no significant signal. Using a pre
      functionalized FO-probe, the technology requires less than 45 minutes for
      measuring a single sample. Comparison of measurements between the biosensor and
      the ELISA revealed an excellent agreement with a Pearson r coefficient of 0.99
      and an intra-class coefficient of 0.99. The reduced assay time and the
      possibility of measuring a single sample are major advantages compared to the
      ELISA. The developed and validated optical adalimumab biosensor could be a
      valuable point-of-care diagnostic tool for adalimumab quantification in patients
      with Crohn's disease.

PMID- 28743170
TI  - Current trends in patient enrollment for robotic-assisted laparoscopic
      prostatectomy in Belgium.
AB  - BACKGROUND: During the last decade, an inverse stage migration has been observed
      in radical prostatectomy series at tertiary centers. However, it remains unclear
      whether similar trends can also be observed in solely robotic practices,
      including nonreferral centers. The aim of this study was to investigate the
      clinical and pathological trends in robotic-assisted laparoscopic prostatectomy
      (RALP) enrollment in Belgium over a period of 6 years through an analysis of a
      prospective registry. METHODS: A prospective, multicenter database was
      constructed: consecutive patients undergoing RALP in Belgium from 2010 to 2015
      were enrolled, and 7366 men were analyzed. Variations in clinical and
      pathological variables were explored as a function of the enrollment year with
      proportional odds for categorical variables and with linear regressions for
      continuous variables. RESULTS: Net increases were observed in the prostate
      specific antigen levels, cT stage, and biopsy Gleason scores across the study
      years (P < .001). The rate of low-risk prostate cancer (PCa) decreased from 36%
      in 2010 to 21% in 2015, whereas the rate of intermediate-risk PCa rose from 47%
      to 58%, and the rate of high-risk PCa rose from 17% to 21%. In parallel, the pT2
      stage rate decreased from 76% to 64%, and the rate of Gleason 6 (3 + 3) cases was
      reduced from 45% to 23% (P < .001). Conversely, the pT3a stage rate rose from 16%
      to 24%, the pT3b stage rate rose from 7% to 11%, and the rate of Gleason 7 (4 +
      3) cases rose from 7% to 21% (P < .0001). Finally, more patients underwent node
      dissection, and positive lymph nodes were increasingly diagnosed (from 3% in 2010
      to 7% in 2015). CONCLUSIONS: During the last 6 years of RALP implementation in
      Belgium, there was a significant increase in the enrollment of intermediate- and
      high-risk PCa patients. This yielded a significant increase in adverse
      pathological characteristics. These results suggest a paradigm shift in PCa
      treatment, with radical robotic surgery increasing for intermediate- and high
      risk patients. Cancer 2017;123:4139-4146. (c) 2017 American Cancer Society.

PMID- 28743171
TI  - A quantified risk-scoring system and rating model for postsurgical gastroparesis
      syndrome in gastric cancer patients.
AB  - BACKGROUND AND OBJECTIVES: The study aimed to investigate the relationship
      between obesity and postsurgical gastroparesis syndrome (PGS), and to construct a
      scoring system and a risk model to identify patients at high risk. METHODS: A
      total of 634 patients were retrospectively analyzed. Clinical characteristics
      were evaluated via receiver operating characteristic (ROC) curve analysis.
      Logistic analysis was performed to determine the independent predictive
      indicators of PGS. A scoring system consisting of these indicators and a risk
      rating model were constructed and evaluated via ROC curve analysis. RESULTS:
      Based on the ROC curves, the visceral fat area (VFA) cutoff value for PGS was
      94.00. Logistic analysis showed that visceral obesity (VFA >= 94.00 cm2 ), the
      reconstruction technique, and tumor size were independent prognostic factors for
      PGS. The scoring system could predict PGS reliably with a high area under the ROC
      curve ([AUC] = 0.769). A high-risk rating had a high AUC (AUC I = 0.56, AUC II =
      0.65, and AUC III = 0.77), indicating that the risk-rating model could
      effectively screen patients at high risk of PGS. CONCLUSIONS: Visceral obesity
      defined by VFA effectively predicted PGS. Our scoring system may be a reliable
      instrument for identifying patients most at risk of PGS.

PMID- 28743172
TI  - Modelling nutritional mutualisms: challenges and opportunities for data
      integration.
AB  - Nutritional mutualisms are ancient, widespread, and profoundly influential in
      biological communities and ecosystems. Although much is known about these
      interactions, comprehensive answers to fundamental questions, such as how
      resource availability and structured interactions influence mutualism
      persistence, are still lacking. Mathematical modelling of nutritional mutualisms
      has great potential to facilitate the search for comprehensive answers to these
      and other fundamental questions by connecting the physiological and genomic
      underpinnings of mutualisms with ecological and evolutionary processes. In
      particular, when integrated with empirical data, models enable understanding of
      underlying mechanisms and generalisation of principles beyond the particulars of
      a given system. Here, we demonstrate how mathematical models can be integrated
      with data to address questions of mutualism persistence at four biological
      scales: cell, individual, population, and community. We highlight select studies
      where data has been or could be integrated with models to either inform model
      structure or test model predictions. We also point out opportunities to increase
      model rigour through tighter integration with data, and describe areas in which
      data is urgently needed. We focus on plant-microbe systems, for which a wealth of
      empirical data is available, but the principles and approaches can be generally
      applied to any nutritional mutualism.

PMID- 28743173
TI  - Improvement and persistent disparities in completion lymph node dissection:
      Lessons from the National Cancer Database.
AB  - BACKGROUND: Completion lymph node dissection (CLND) is recommended for melanoma
      patients with positive sentinel lymph node biopsies (SLNB); however, 50% do not
      undergo CLND. We sought to determine CLND trends over time, and factors
      contributing to variability. METHODS: The NCDB was queried for patients
      undergoing wide local excision (WLE), with or without SLNB and CLND. Cohorts were
      created based on demographic/socioeconomic variables and era of treatment (Era 1:
      2003-07, Era 2: 2008-12). Univariate and multivariate analyses identified factors
      associated with performance of or trends in CLND. RESULTS: 122 849 underwent WLE
      with SLNB. Of 24 267 (19.8%) with +SLNB, 13 594 (56.0%) continued to CLND. In
      multivariate analyses, Medicaid (OR 0.78; P = 0.04) or Medicare (OR 0.79; P <
      0.01) in Era 1 and patients without insurance in Era 2 (OR 0.78; P = 0.01)
      underwent less CLND. In both eras, Blacks (OR 0.45; P < 0.01, OR 0.59; P < 0.01),
      head/neck lesions (OR 0.72; P < 0.01, OR 0.66; P < 0.01) and lower extremity
      lesions (OR 0.75; P < 0.01, OR 0.72; P < 0.01) underwent less CLND. However,
      Blacks experienced greatest increase in CLND usage (+9.2%). CONCLUSIONS: CLND
      usage continues to be low and racial/socioeconomic disparities persist. Until the
      results of MSLT-2 become available, continued focus on understanding poor
      adherence to, and improving rates of CLND is necessary.

PMID- 28743175
TI  - Rituximab therapy and the highly polymorphic Fc region of IgG: comment on the
      article by Cartin-Ceba et al.

PMID- 28743174
TI  - The effectiveness of a group intervention to facilitate posttraumatic growth
      among women with breast cancer.
AB  - OBJECTIVE: This longitudinal study tested the effectiveness of a group
      intervention designed to facilitate posttraumatic growth (PTG). METHODS: Sample
      consisted of 205 women diagnosed with non-metastatic breast cancer who were
      either assigned to an intervention group (n = 58) or to a control group (n =
      147). PTG, challenge to core beliefs, and rumination (intrusive and deliberate)
      were assessed at baseline (T1), at 6 months (T2), and at 12 months after baseline
      (T3). RESULTS: Results from the Latent Growth Modeling suggested that
      participants from the intervention group have higher levels of PTG. The challenge
      to core beliefs and the intrusive rumination have a moderator role on PTG, since
      group intervention is also linked to the enhancement of both variables.
      CONCLUSIONS: Participation in the intervention group increase PTG. Challenge to
      core beliefs and intrusive rumination are improved by group intervention, which
      to a certain extent facilitate PTG.

PMID- 28743176
TI  - Technique of skeletal navigation for localizing solitary pulmonary nodules.
AB  - We herein detail a novel method of skeletal navigation for localizing small
      solitary pulmonary nodules of 8-30 mm size and at a distance of less than 15 mm
      from visceral pleura. Thirty-four lesions found in 29 patients were successfully
      localized. All 34 target nodules first underwent wedge resections, and there were
      no cases of technical failure of the present method. This technique incurs no
      additional cost and complications as caused by other localization approaches.
      Additionally, this approach provides a backup method in cases of mark
      displacement.

PMID- 28743177
TI  - Traditional suburethral sling operations for urinary incontinence in women.
AB  - BACKGROUND: Stress urinary incontinence constitutes a significant health and
      economic burden to society. Traditional suburethral slings are one of the
      surgical operations used to treat women with symptoms of stress urinary
      incontinence. OBJECTIVES: To determine the effects of traditional suburethral
      slings on stress or mixed incontinence in comparison with other management
      options. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised
      Register (searched 3 June 2010) and the reference lists of relevant articles.
      SELECTION CRITERIA: Randomised or quasi-randomised trials that included
      traditional suburethral slings for the treatment of stress or mixed urinary
      incontinence. DATA COLLECTION AND ANALYSIS: At least three reviewers
      independently extracted data from included trials onto a standard form and
      assessed trial methodological quality. The data abstracted were relevant to
      predetermined outcome measures. Where appropriate, we calculated a summary
      statistic: a relative risk for dichotomous data and a weighted mean difference
      for continuous data. MAIN RESULTS: We included 26 trials involving 2284 women.
      The quality of evidence was moderate for most trials and there was generally
      short follow-up ranging from 6 to 24 months.One medium-sized trial compared
      traditional suburethral sling operations with oxybutynin in the treatment of
      women with mixed urinary incontinence. Surgery appeared to be more effective than
      drugs in treating participant-reported incontinence (n = 75, risk ratio (RR)
      0.18, 95% confidence interval (CI) 0.08 to 0.43).One trial found that traditional
      slings were more effective than transurethral injectable treatment (RR for
      clinician-assessed incontinence within a year 0.21, 95% CI 0.09 to 0.21)Seven
      trials compared slings with open abdominal retropubic colposuspension.
      Participant-reported incontinence was lower with the slings after one year (RR
      0.75, 95% CI 0.62 to 0.90), but not when assessed by clinicians. Colposuspension,
      however, was associated with fewer peri-operative complications, shorter duration
      of use of indwelling catheter and less long-term voiding dysfunction. One study
      showed there was a 20% lower risk of bladder perforation with the sling procedure
      but a 50% increase in urinary tract infection with the sling procedure compared
      with colposuspension. Fewer women developed prolapse after slings (compared with
      after colposuspension) in two small trials but this did not reach statistical
      significance.Twelve trials addressed the comparison between traditional sling
      operations and minimally invasive sling operations. These seemed to be equally
      effective in the short term (RR for incontinence within first year 0.97, 95% CI
      0.78 to 1.20) but minimally invasive slings had a shorter operating time, fewer
      peri-operative complications (other than bladder perforation) and some evidence
      of less post-operative voiding dysfunction and detrusor symptoms.Six trials
      compared one type of traditional sling with another. Materials included porcine
      dermis, lyophilised dura mater, fascia lata, vaginal wall, autologous dermis and
      rectus fascia. Participant-reported improvement rates within the first year
      favoured the traditional autologous material rectus fascia over other biological
      materials (RR 0.45, 95% CI 0.21 to 0.98). There were more complications with the
      use of non-absorbable Gore-Tex in one trial.Data for comparison of bladder neck
      needle suspension with suburethral slings were inconclusive because they came
      from a single trial with a small specialised population.No trials compared
      traditional suburethral slings with anterior repair, laparoscopic retropubic
      colposuspension or artificial sphincters. Most trials did not distinguish between
      women having surgery for primary or recurrent incontinence when reporting
      participant characteristics.For most of the comparisons, clinically important
      differences could not be ruled out. AUTHORS' CONCLUSIONS: Traditional slings seem
      to be as effective as minimally invasive slings, but had higher rates of adverse
      effects. This should be interpreted with some caution however, as the quality of
      evidence for the studies was variable, follow-up short and populations small,
      particularly for identifying complication rates. Tradional sling procedures
      appeared to confer a similar cure rate in comparison to open retropubic
      colposuspension, but the long-term adverse event profile is still unclear. A
      brief economic commentary (BEC) identified two studies suggesting that
      traditional slings may be more cost-effective compared with collagen injection
      but not cost-effective when compared with minimally invasive sling operations.
      Reliable evidence to clarify whether or not traditional suburethral slings may be
      better or worse than other surgical or conservative management options is
      lacking.

PMID- 28743178
TI  - Multicenter analysis of transanal tube placement for prevention of anastomotic
      leak after low anterior resection.
AB  - BACKGROUND: Anastomotic leak (AL) is a serious complication of low anterior
      resection (LAR). This study aimed to evaluate the effect of transanal tube
      placement for prevention of AL. METHODS: This multicenter retrospective cohort
      study enrolled 328 consecutive patients who underwent LAR for rectal cancer at
      participating hospitals from 2009 to 2014. Multivariate logistic regression was
      used to adjust for confounding factors. RESULTS: A transanal tube was placed in
      205 patients (TA group) and not placed in 123 patients (non-TA group).
      Symptomatic AL occurred in 36 cases (11%), with significantly higher incidence of
      symptomatic AL in the non-TA group than in the TA group (15% vs 8.3%, odds ratio
      [OR] 2.02, 95% confidence interval [CI] 1.01-4.06). After adjusting for
      confounding factors, multivariate analysis revealed that placement of a transanal
      tube could decrease the incidence of symptomatic AL (adjusted OR 0.37, 95%CI 0.15
      0.91). There was no significant difference in postoperative morbidity, mortality,
      length of hospital stay, or local recurrence rate between the two groups. Local
      recurrence rate tended to be higher in patients with symptomatic AL (3/36) than
      in those without it (10/292). CONCLUSIONS: Transanal tube placement is effective
      for decreasing the incidence of symptomatic AL after LAR.

PMID- 28743179
TI  - Prevalence of psychiatric comorbidities among women undergoing free tissue
      autologous breast reconstruction.
AB  - BACKGROUND AND OBJECTIVES: Autologous breast reconstruction (BR) can be a
      stressful life event. Therefore, women undergoing mastectomy and autologous BR
      are required to have sufficient coping mechanisms. Although mental health
      problems are widespread, information regarding the prevalence of psychiatric
      diagnosis among these patients is scarce. METHODS: Retrospective analysis was
      performed using data from a large tertiary teaching hospital and the Nationwide
      Inpatient Sample (NIS) database. Patients undergoing autologous BR after
      mastectomy were included and evaluated for psychiatric disorders. Prevalence of
      each disorder, timing of diagnosis (preoperative or postoperative), and data per
      age group were reviewed. RESULTS: Between 2004 and 2014, 817 patients were
      included from the institutional database and 26 399 from the NIS database.
      Preoperatively, 15.3% of the patients were diagnosed with a psychiatric disorder
      within our institution and 17.6% nationwide (P < 0.001). Postoperatively, 20.5%
      of the institutional patients were diagnosed with a psychiatric disorder. No
      major differences in prevalence were seen between age groups. CONCLUSIONS:
      Approximately, one in six patients were diagnosed with a psychiatric comorbidity
      preoperatively. Postoperatively, an additional 20.5% developed a psychiatric
      disorder. There was no difference in prevalence and timing of diagnosis between
      age groups.

PMID- 28743180
TI  - Factors predictive of occult nipple-areolar complex involvement in patients with
      carcinoma in situ of the breast.
AB  - OBJECTIVES: To investigate predictors of occult nipple-areolar complex (NAC)
      involvement in patients with carcinoma in situ (CIS) and to validate an online
      probability calculator (CancerMath;
      www.lifemath.net/cancer/breastcancer/nipplecalc/index.php). METHODS:
      Mastectomized patients with CIS (n = 104) were retrospectively selected.
      Clinicopathology and preoperative mammography, ultrasound, and magnetic resonance
      imaging (MRI) findings were analyzed. RESULTS: Histopathological NAC-positivity
      was confirmed in 20 (19.2%) patients. Short nipple-tumor distance and suspicious
      extension to the nipple by mammography were significant but ultrasound was not
      significant to predict NAC involvement. NAC-positive cases had MRI findings of
      shorter nipple-tumor distance in both the early and delayed phases. Multivariable
      regression model showed age >50 years and shorter tumor-nipple distance on the
      delay phase of MRI were statistically significant predictors of NAC involvement.
      Area under the receiver operating characteristics curve (AUC) was 0.618 when
      calculated by CancerMath; however, an AUC of 0.954 was achieved when distance and
      age were applied together as predictor. CONCLUSIONS: Mammographic and MRI
      findings were significant for predicting NAC involvement, with distance of the
      tumor from the nipple in delay phase MRI the most significant predictor of NAC
      involvement. Therefore, breast MRI could be beneficial for planning nipple
      sparing mastectomy in patients with CIS.

PMID- 28743181
TI  - Feasibility and safety of hyperthermic intraperitoneal chemotherapy using 5
      fluorouracil combined with cisplatin and mitomycin C in patients undergoing
      gastrectomy for advanced gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: We conducted a dose-finding study for 5-fluorouracil
      (5-FU) administered with cisplatin (CDDP) and mitomycin C (MMC) to find an
      improved regimen for hyperthermic intraperitoneal chemotherapy (HIPEC) for
      advanced gastric cancer (GC). METHODS: The appropriate HIPEC regimen previously
      determined in vitro was 5-FU (200 ug/mL), MMC (2 ug/mL), and CDDP (10 ug/mL) at
      hyperthermic conditions (42 degrees C) for 30 min. This was a clinical study to
      determine the recommended dose of 5-FU in combination with MMC and CDDP at 42
      degrees C for 30 min and to evaluate HIPEC safety in patients at high risk of
      developing peritoneal metastases following GC surgery. RESULTS: Twelve patients
      were treated with surgery plus HIPEC using 5-FU at 0, 500, 750, and 1000 mg
      combined with MMC (10 mg) and CDDP (50 mg) in the perfusate (5 L). Dose-limiting
      toxicities did not develop until 1000 mg 5-FU was reached. Four patients
      experienced grade 1 or 2 adverse events. The recommended dose was 1000 mg 5-FU/5
      L perfusate. Eight (66.7%) patients demonstrated no recurrence of peritoneal
      metastases; 5-year overall survival rate was 83.3%. CONCLUSION: Gastrectomy and
      HIPEC with MMC, CDDP, and 5-FU is feasible, safe, and may protect against
      peritoneal metastasis following surgery for advanced GC.

PMID- 28743182
TI  - Crosstalk and Interplay between the Ubiquitin-Proteasome System and Autophagy.
AB  - Proteolysis in eukaryotic cells is mainly mediated by the ubiquitin (Ub)
      proteasome system (UPS) and the autophagylysosome system (hereafter autophagy).
      The UPS is a selective proteolytic system in which substrates are recognized and
      tagged with ubiquitin for processive degradation by the proteasome. Autophagy is
      a bulk degradative system that uses lysosomal hydrolases to degrade proteins as
      well as various other cellular constituents. Since the inception of their
      discoveries, the UPS and autophagy were thought to be independent of each other
      in components, action mechanisms, and substrate selectivity. Recent studies
      suggest that cells operate a single proteolytic network comprising of the UPS and
      autophagy that share notable similarity in many aspects and functionally
      cooperate with each other to maintain proteostasis. In this review, we discuss
      the mechanisms underlying the crosstalk and interplay between the UPS and
      autophagy, with an emphasis on substrate selectivity and compensatory regulation
      under cellular stresses.

PMID- 28743183
TI  - Driving CO2 to a Quasi-Condensed Phase at the Interface between a Nanoparticle
      Surface and a Metal-Organic Framework at 1 bar and 298 K.
AB  - We demonstrate a molecular-level observation of driving CO2 molecules into a
      quasi-condensed phase on the solid surface of metal nanoparticles (NP) under
      ambient conditions of 1 bar and 298 K. This is achieved via a CO2 accumulation in
      the interface between a metal-organic framework (MOF) and a metal NP surface
      formed by coating NPs with a MOF. Using real-time surface-enhanced Raman
      scattering spectroscopy, a >18-fold enhancement of surface coverage of CO2 is
      observed at the interface. The high surface concentration leads CO2 molecules to
      be in close proximity with the probe molecules on the metal surface (4
      methylbenzenethiol), and transforms CO2 molecules into a bent conformation
      without the formation of chemical bonds. Such linear-to-bent transition of CO2 is
      unprecedented at ambient conditions in the absence of chemical bond formation,
      and is commonly observed only in pressurized systems (>105 bar). The molecular
      level observation of a quasi-condensed phase induced by MOF coating could impact
      the future design of hybrid materials in diverse applications, including
      catalytic CO2 conversion and ambient solid-gas operation.

PMID- 28743184
TI  - Surface Fluorination of Reactive Battery Anode Materials for Enhanced Stability.
AB  - Significant increases in the energy density of batteries must be achieved by
      exploring new materials and cell configurations. Lithium metal and lithiated
      silicon are two promising high-capacity anode materials. Unfortunately, both of
      these anodes require a reliable passivating layer to survive the serious
      environmental corrosion during handling and cycling. Here we developed a surface
      fluorination process to form a homogeneous and dense LiF coating on reactive
      anode materials, with in situ generated fluorine gas, by using a fluoropolymer,
      CYTOP, as the precursor. The process is effectively a "reaction in the beaker",
      avoiding direct handling of highly toxic fluorine gas. For lithium metal, this
      LiF coating serves as a chemically stable and mechanically strong interphase,
      which minimizes the corrosion reaction with carbonate electrolytes and suppresses
      dendrite formation, enabling dendrite-free and stable cycling over 300 cycles
      with current densities up to 5 mA/cm2. Lithiated silicon can serve as either a
      pre-lithiation additive for existing lithium-ion batteries or a replacement for
      lithium metal in Li-O2 and Li-S batteries. However, lithiated silicon reacts
      vigorously with the standard slurry solvent N-methyl-2-pyrrolidinone (NMP),
      indicating it is not compatible with the real battery fabrication process. With
      the protection of crystalline and dense LiF coating, LixSi can be processed in
      anhydrous NMP with a high capacity of 2504 mAh/g. With low solubility of LiF in
      water, this protection layer also allows LixSi to be stable in humid air (~40%
      relative humidity). Therefore, this facile surface fluorination process brings
      huge benefit to both the existing lithium-ion batteries and next-generation
      lithium metal batteries.

PMID- 28743185
TI  - Introduction: Carbon Capture and Separation.

PMID- 28743187
TI  - Severely Affected by Parkinson Disease: The Patient's View and Implications for
      Palliative Care.
AB  - INTRODUCTION: People severely affected by Parkinson disease (PD)/atypical
      parkinsonism (AP) comprise a heterogeneous group with distinct needs, which so
      far remain largely unexamined. The aim of our study was to analyze reasons for
      feeling severely affected and document unmet needs in a patient subgroup severely
      affected by PD/AP using solely a subjective inclusion criterion. METHODS:
      Patients feeling severely affected by PD/AP were recruited via a magazine
      published by the German Parkinson Association. A questionnaire was sent out
      nationwide. Besides analyzing the closed-ended questions, a subsample of 40% was
      analyzed regarding the open-ended questions using content analysis. Correlations
      between subjectively felt severe affectedness and objective criteria were
      calculated. RESULTS: Eight hundred fourteen questionnaires were analyzed. Sample
      characteristics were: mean age 70 years; 60.3% male; time since diagnosis up to
      37 years; and Hoehn and Yahr score (if known) 3 (44.6%), followed by 4 (23.9%).
      Significant associations were observed between subjectively felt severe
      affectedness and Hoehn and Yahr ( P <= .05), poorer health ( P <= .01), higher
      nursing care level ( P <= 0.01), and having no children ( P <= .05). Most common
      reasons for feeling severely affected were mobility impairment (34.9%),
      coordination problems (17.0%), speech problems (12.2%), and limited day-to-day
      activities (7.8%). Most often expressed unmet needs were support in everyday life
      (28.1%), medical treatment (15.2%), help with financial services (11.6%), and
      social integration (9.9%). CONCLUSIONS: To meet the complex needs, an integrated
      multidisciplinary and multiprofessional approach is indicated befitting
      palliative care principles. Herein, home-based services seem of special
      importance for patients in advanced disease stages.

PMID- 28743188
TI  - Nanocomposite hydrogels for cartilage tissue engineering: a review.
AB  - The loss of cartilaginous tissues is an important challenge to orthopaedic
      surgeons. Injury to cartilage tissue due to its properties is along with movement
      difficulties. Tissue engineering is a developing field that can be used for
      regeneration or replacement of damaged tissues. In this field, an appropriate
      scaffold that support the recruitment, adhesion, proliferation and
      differentiation of cells is necessary. Hydrogels recently considered as materials
      that resemble the extracellular matrix (ECM) and efficiently replace defective
      tissues, but they have limited mechanical strength. So nanomaterials are embedded
      in the hydrogel's matrix to improve their properties. Nanoparticles, such as
      organic/polymeric and inorganic (hydroxyapatite, clay, graphene and metallic
      nanoparticles), can be used as fillers to reinforce the hydrogel matrix.
      Utilizing those nanocomposites could help in better performance of hydrogels
      applicable in cartilage regeneration practices. This review presents some of
      nanocomposite hydrogel (NCH) systems that used in cartilage tissue engineering.

PMID- 28743189
TI  - Response to Kerr et al.

PMID- 28743190
TI  - Effect of Obstructive Sleep Apnea Treatment on Renal Function in Patients with
      Cardiovascular Disease.
AB  - RATIONALE: Obstructive sleep apnea (OSA) is associated with impaired renal
      function, but uncertainty exists over whether OSA treatment can influence renal
      outcomes. OBJECTIVES: To determine the effects of continuous positive airway
      pressure (CPAP) on renal function in subjects with coexisting OSA and
      cardiovascular disease. METHODS: This was a substudy of the international SAVE
      (Sleep Apnea Cardiovascular Endpoints) trial, in which 2,717 patients with
      moderate to severe OSA and established coronary or cerebrovascular disease were
      randomized to receive either CPAP plus usual care or usual care alone. Renal
      function and adverse renal events were compared between the CPAP (n = 102) and
      usual care (n = 98) groups. Glomerular filtration rate was estimated at
      randomization and at the end of follow-up, and the urinary albumin-to-creatinine
      ratio was measured at study exit. MEASUREMENTS AND MAIN RESULTS: In 200 substudy
      participants (mean age, 64 yr; median, 4% oxygen desaturation index; 20 events/h;
      mean estimated glomerular filtration rate at baseline, 82 ml/min/1.73 m2), the
      median (interquartile range) changes in estimated glomerular filtration rate
      (ml/min/1.73 m2/yr) were -1.64 (-3.45 to -0.740) in the CPAP group and -2.30 (
      4.53 to -0.71) in the usual care group (P = 0.21) after a median of 4.4 years.
      There were no between-group differences in end-of-study urinary albumin-to
      creatinine ratio or in the occurrence of serious renal or urinary adverse events
      during the trial. The level of CPAP adherence did not influence the findings.
      CONCLUSIONS: CPAP treatment of OSA in patients with cardiovascular disease does
      not alter renal function or the occurrence of renal adverse events. Clinical
      trial registered with www.clinicaltrials.gov (NCT00738179).

PMID- 28743191
TI  - Successful utilization of an electronic pain diary in a multinational phase 3
      interventional study of pediatric sickle cell anemia.
AB  - BACKGROUND/AIMS: Patients with sickle cell anemia can experience recurrent pain
      episodes, which affect quality of life. The reported prevalence of pain is higher
      in studies using patient diaries than in healthcare facility utilization data.
      Determining Effects of Platelet Inhibition on Vaso-Occlusive Events was a
      multinational study that assessed the efficacy and safety of prasugrel in
      reducing the rate of vaso-occlusive events in children with sickle cell anemia
      (NCT01794000) and included an electronic patient-reported outcome diary to record
      pain occurrence. We aimed to capture diary completion rates and compliance in
      children who used the electronic patient-reported outcome diary during the
      Determining Effects of Platelet Inhibition on Vaso-Occlusive Events study and
      examine factors contributing to diary completion rates and compliance. METHODS:
      Daily electronic patient-reported outcome diary data were collected for up to 9
      months in Determining Effects of Platelet Inhibition on Vaso-Occlusive Events
      participants aged 4 to <18 years in Africa, the Americas, Europe, and the Middle
      East. The questionnaires were available in 11 languages/dialects for collecting
      subjective (pain intensity, activity interference) and objective (study drug use,
      analgesic use, school attendance) data. Pain intensity was measured using the
      Faces Pain Scale-Revised. Data were entered by participants or caregivers and
      transferred wirelessly each day to a central database. Diary completion rates
      were the number of daily diary entries divided by the total number of expected
      daily diary entries. Percentages of participants who were compliant with the
      diary (>=80% diary completion) were calculated. RESULTS: A total of 311
      participants received a diary; 268 provided diary data through Month 9. Diary
      completion rates and compliance were high throughout the collection period and
      across all groups and regions, despite no games being included on the device. For
      subjective data, the overall completion rate was 94.4%, and 92.6% of participants
      were compliant. For objective data, the overall completion rate was 93.3%, and
      89.7% of participants were compliant. Completion rates and compliance differed
      significantly by age and region and were higher for 4 to <12 year olds and very
      much higher for participants from Africa and the Middle East. Caregivers almost
      always entered data for participants <6 years and rarely entered data for
      participants >=12 years. Comparing participant-entered and caregiver-entered
      data, pain intensity score data were more consistent for 4 to <12 year olds than
      older children, but pain intensity scores for older children were higher when
      entered by caregivers. CONCLUSION: With appropriate design, participant training,
      and sufficient monitoring, an electronic patient-reported outcome diary can
      capture daily sickle cell-related pain data in large multinational studies.
      Providing a mechanism for caregiver reporting is particularly valuable for
      participants <6 years and may also facilitate compliance in older children who
      experience high levels of pain.

PMID- 28743192
TI  - Searching for Evidence of an Anti-Inflammatory Diet in Children: A Systematic
      Review of Randomized Controlled Trials for Pediatric Obesity Interventions With a
      Focus on Leptin, Ghrelin, and Adiponectin.
AB  - PROBLEM: To address the complex phenomenon of pediatric obesity, one must
      understand the physiological mechanisms regulating energy intake and
      inflammation. The peptide hormones leptin, ghrelin, and adiponectin are involved
      in both, but their functions are dysregulated in obesity. The purpose of this
      systematic review is (1) to characterize studies of nutrition interventions for
      weight management in children who measure these peptides as outcomes, (2) to
      assess risk of bias in the studies, and (3) to determine the relationships
      between these peptides and body mass index (BMI). Eligibility Criteria: Peer
      reviewed articles written in English, published in 2001-2016, and describing
      randomized controlled trials of pediatric interventions involving a nutrition
      component with the outcome measures leptin, ghrelin, and/or adiponectin were
      included. Articles were excluded if the intervention involved pharmaceuticals,
      supplements, infant formula, breastfeeding, or surgery. SAMPLE: The 25
      international studies represented 2,153 obese children. RESULTS: Ten diets were
      identified. Successful interventions included both structured exercise and
      hypocaloric dietary components, with or without counseling, resistance training,
      or medical components. Direct measures of adiposity were used in 69% of studies.
      Comparison group designs were disparate. Leptin levels decreased as BMI
      decreased. Evidence regarding the relationships of ghrelin and adiponectin with
      BMI was inconclusive. CONCLUSIONS: Despite known effects of maturation on
      hormones, studies did not consistently differentiate findings by maturational
      stage. Common anti-inflammatory and disease risk modification diets were missing
      or underrepresented. Studies that include children with comorbidities are needed.
      BMI and leptin levels have a positive relationship, but evidence on ghrelin and
      adiponectin was inconclusive.

PMID- 28743194
TI  - Corrigendum.

PMID- 28743193
TI  - Is polysomnography screening effective for stroke prevention?

PMID- 28743195
TI  - Examining the relationship between post-traumatic stress disorder and social
      participation among Veterans with spinal cord injuries and disorders.
AB  - PURPOSE: The objectives of this study were to examine differences in social
      participation among Veterans with spinal cord injuries/disorders with and without
      post-traumatic stress disorder, and determine if lower social participation was
      independently associated with having post-traumatic stress disorder. METHODS: A
      cross-sectional mailed national survey was sent to a national sample of Veterans
      with spinal cord injuries/disorders who received prior-year Veterans Affairs
      healthcare. Surveys provided data on: demographics, health conditions, injury
      characteristics, and social participation. Analyses included bivariate
      comparisons, and multivariate logistic regression to determine if lower social
      participation was independently associated with post-traumatic stress disorder.
      RESULTS: Veterans with (vs. without) post-traumatic stress disorder (n = 896)
      reported lower social participation (40.2 vs. 43.9, p < 0.0001). Multivariate
      analyses showed that longer duration of injury (OR = 0.98, 95% CI: 0.97-1.00, p =
      0.04) and white race (OR = 0.62, 95% CI: 0.38-1.01, p = 0.05) were associated
      with lower odds of post-traumatic stress disorder, while a greater number of
      health conditions (OR = 1.43, 95% CI: 1.25-1.64, p < 0.0001) was associated with
      greater odds. When controlling for covariates, lower social participation was
      independently associated with post-traumatic stress disorder (OR = 0.94, 95% CI:
      0.90-0.98, p = 0.003). CONCLUSIONS: Results indicate post-traumatic stress
      disorder is associated with lower social participation in Veterans with spinal
      cord injuries/disorders, independent of other factors that may impact
      participation. Efforts to screen for and treat post-traumatic stress disorder
      among persons with spinal cord injuries/disorders, regardless of injury-specific
      factors, are needed to improve participation. Implications for Rehabilitation
      Individuals with spinal cord injuries/disorders often have post-traumatic stress
      disorder; in Veterans with spinal cord injuries/disorders this may be compounded
      by trauma incurred through military experiences. Social participation, an
      important aspect of rehabilitation and community integration following spinal
      cord injury or disorder, may be hindered by symptoms of post-traumatic stress
      disorder. Our data show that post-traumatic stress disorder is associated with
      lower social participation in Veterans with spinal cord injuries/disorders,
      independent of other factors that may impact participation. These results
      indicate that efforts to screen for and treat post-traumatic stress disorder
      among persons with spinal cord injuries/disorders, regardless of injury-specific
      factors, are needed to improve participation in this patient population.

PMID- 28743196
TI  - Evaluation of sequential effect of isotretinoin on the haematological parameters
      in patients with acne vulgaris.
AB  - PURPOSE: Isotretinoin is the most effective drug for acne with some side effects.
      Few studies exist regarding the effects of isotretinoin on haematological
      parameters with different results. Mostly, baseline values with a single value
      during or at the end of the treatment were compared. In this study, we aimed to
      determine the differences in haematological parameters during isotretinoin
      treatment until reaching the cumulative dose of 120 mg/kg. MATERIALS AND METHODS:
      The study included 118 patients with moderate-to-severe acne vulgaris. Patients
      with preexisting liver disease, anaemia, iron deficiency, abnormal liver function
      tests, thrombocytopenia/thrombocytosis or hyperlipidaemia were excluded.
      Laboratory monitoring for haematological parameters was performed at baseline and
      monthly during treatment. Parameters at the baseline, at the first and second
      months and at the end of the therapy were taken into account. RESULTS: According
      to general linear model analysis, platelets and plateletcrit increased at the
      first month of the treatment and then decreased to baseline. White blood cells
      and neutrophils decreased at the first month, then increased to baseline value at
      the second month, and were found to be decreased again at the end of the
      treatment. Mean corpuscle volume was found to be increased at the end of the
      treatment. Other parameters in CBC did not show statistically significant
      differences. CONCLUSIONS: Although some changes occur in haematological
      parameters during isotretinoin therapy, all of these changes remain within the
      normal range. Evaluating the spot values at any time during treatment may cause
      misinterpretations.

PMID- 28743197
TI  - Evaluation of Parkinson's disease by neuromelanin-sensitive magnetic resonance
      imaging and 123I-FP-CIT SPECT.
AB  - Background Both neuromelanin-sensitive magnetic resonance imaging (NmMRI) and
      123I-FP-CIT single photon emission computed tomography (SPECT) (DaTSCAN) assist
      the diagnosis of Parkinson's disease (PD). However, there have been few studies
      investigating a correlation between them. Purpose To correlate the utility of
      NmMRI and DaTSCAN and to evaluate the relationship between both imaging findings
      and the Unified PD rating scale part III (UPDRS III) score for the diagnosis and
      management of PD. Material and Methods Seventeen patients with PD who underwent
      both NmMRI and DaTSCAN were included. We measured the volume of the neuromelanin
      positive substantia nigra pars compacta (SNc volume) on NmMRI and measured the
      specific binding ratio (SBR) on DaTSCAN. The asymmetry index (AI) of the SNc
      volume and SBR were also calculated. We evaluated the relationship between the
      UPDRS III score and the SNc volume and SBR, respectively. Results The SNc volume
      showed a significant correlation with the SBR. The AIs of them also showed a
      significant correlation. Both the mean of the bilateral SBR and the mean of the
      bilateral SNc volume showed significant negative correlations with the UPDRS III
      score. However, the correlation between the SBR and the UPDRS III score was
      stronger than that between the SNc volume and the UPDRS III score. Conclusion
      Both NmMRI and DaTSCAN are helpful for PD diagnosis. However, we conclude that
      DaTSCAN is more suitable for the evaluation of the clinical motor severity and
      would be more useful for the management of PD patients than NmMRI.

PMID- 28743198
TI  - Do Acute Benefits of Interpersonal Psychotherapy for Posttraumatic Stress
      Disorder Endure?
AB  - OBJECTIVE: The Psychotherapies for Chronic PTSD randomised trial found that three
      14-week psychotherapies acutely benefitted patients with chronic posttraumatic
      stress disorder (PTSD). Previous research has reported sustained follow-up
      benefits for prolonged exposure (PE) and relaxation therapy (RT), but few
      comparable data exist for interpersonal psychotherapy (IPT). We describe 3-month
      follow-up for acute responders to all 3 treatments. METHOD: Acute responders,
      defined a priori as >=30% improved from baseline, were reevaluated after 3-month
      no-treatment follow-up by independent evaluators using the Clinician-Administered
      PTSD Scale (CAPS). RESULTS: Fifty of 110 initial study entrants met acute
      responder status at week 14. Forty-three (86%) responders entered follow-up: 23
      remitters (CAPS <=20) and 20 responders. At week 26, 27 had achieved remission
      status, 10 remained responders, and 6 had relapsed. Of week 14 remitters, 8 of 9
      PE, all 8 IPT, and 4 of 6 RT patients remained remitted. Relapse rates were 7%
      (1/9) for PE, 10% (2/20) for IPT, and 33% (3/9) for RT. At week 26, PE showed
      greater improvement on CAPS than RT ( P = 0.048) and a trend for superiority over
      IPT ( P = 0.098), with no significant difference between IPT and RT. Depressive
      symptoms remained low during follow-up. CONCLUSIONS: These are the first
      systematic data on follow-up responder status and persistence of acute treatment
      benefits in patients receiving individual IPT for chronic PTSD. Patients
      generally maintained gains across treatments, fluctuating most in RT. Study
      limitations include small sample size and brief follow-up interval. PTSD research
      should employ response and remission criteria.

PMID- 28743199
TI  - 3,4-Methylenedioxymethamphetamine causes cytotoxicity on 661W cells through
      inducing macrophage polarization.
AB  - The abuse of 3,4-methylenedioxymethamphetamine (MDMA), a psychedelic drug, can
      lead to a variety of disorders in neural system, including the death of retinal
      neural cells. MDMA at lower doses does not cause obvious cytotoxicity to
      photoreceptor cells, indicating potential indirect mechanisms which have not yet
      been elucidated. This study investigated the effect of MDMA at nontoxic
      concentration on macrophage activation state and its resultant toxicity to
      photoreceptor cells. Using a co-culture system, cytotoxicity was caused by MDMA
      on 661W cells after co-culturing with RAW264.7 macrophage. Results showed that
      MDMA induced the macrophages to M1 polarization, releasing more pro-inflammatory
      cytokines, upregulating the M1-related gene and protein expression. The
      phenotype, secretion pattern, and cytotoxicity of the macrophages treated by MDMA
      are comparable to those of the ones stimulated by IFNgamma and LPS. Our study
      demonstrated that MDMA promoted macrophage polarization to M1 and induced
      inflammatory response, providing the scientific rationale for the photoreceptor
      cell damage caused by the MDMA abuse.

PMID- 28743200
TI  - Green fluorescent protein (GFP): is seeing believing and is that enough?
AB  - Intracellular compartmentalisation is a significant barrier to the successful
      nucleocytosolic delivery of biologics. The endocytic system has been shown to be
      responsible for compartmentalisation, providing an entry point, and trigger(s)
      for the activation of drug delivery systems. Consequently, many of the
      technologies used to understand endocytosis have found utility within the field
      of drug delivery. The use of fluorescent proteins as markers denoting
      compartmentalisation within the endocytic system has become commonplace. Several
      of the limitations associated with the use of green fluorescent protein (GFP)
      within the context of drug delivery have been explored here by asking a series of
      related questions: (1) Are molecules that regulate fusion to a specific
      compartment (i.e. Rab- or SNARE-GFP fusions) a good choice of marker for that
      compartment? (2) How reliable was GFP-marker overexpression when used to define a
      given endocytic compartment? (3) Can glutathione-s-transferase (GST) fused in
      frame with GFP (GST-GFP) act as a fluid phase endocytic probe? (4) Was GFP
      fluorescence a robust indicator of (GFP) protein integrity? This study concluded
      that there are many appropriate and useful applications for GFP; however, thought
      and an understanding of the biological and physicochemical character of these
      markers are required for the generation of meaningful data.

PMID- 28743201
TI  - Pharyngotomy in head and neck squamous cell carcinoma: functional and oncological
      aspects.
AB  - BACKGROUND: Head and Neck Surgery constantly has to oppose non-invasive organ
      preservation methods and therefore should be evaluated especially with regard to
      clinical and functional outcome. We will discuss the role of pharyngotomy in the
      treatment of HNSCC. METHODS: Seventy-three patients with carcinoma of the oral
      cavity, oro-/hypopharynx and supraglottis underwent lateral/median pharyngotomy.
      Functional and oncological parameters were retrospectively assessed and set into
      clinical context. RESULTS: The 5-year recurrence-free-interval (RFI) was
      significantly higher with surgery and adjuvant radio(chemo)therapy (80%; mean
      RFI: 92 months) when compared to conservative treatment (68%; mean RFI: 68
      months). The 5-year overall-survival (OS) after surgery and conservative
      treatment was 71% and 54%, respectively. Compared to other surgical techniques
      (mean RFI: 82 months), pharyngotomy demonstrated a significant higher 5-year RFI
      (mean RFI: 89 months). CONCLUSIONS: Pharyngotomy achieves good exposure and clear
      resection margins that result in a notably good oncological outcome with a
      minimum of functional loss. In particular, among UICC IV oropharyngeal HNSCC,
      pharyngotomy is superior in OS and RFI to conservative methods.

PMID- 28743202
TI  - Is fertility associated with the number of siblings of the couple? Evidence from
      India.
AB  - The influence of family on an individual's fertility has long been an important
      topic of interest in fertility research. Although studies conducted mostly in
      developed countries found a significant bearing of fertility of the parents on
      the fertility of the children, there is a lack of formal research around this
      topic in India. The present study analyses the effect of sibling size of husband
      and wife on the completed family size of women using information of 5506 ever
      married women aged 45-49 years incorporated in the India Human Development Survey
      II (2011-2012). Inferential statistics, bivariate, Chi-square and Poisson
      regression were used as the methods of analysis. The unadjusted estimates of
      Poisson regression reveal sibling size of women (IRR: 1.02; p < 0.001) and
      husband (IRR: 1.01; p < 0.001) have a positive correlation with the completed
      family size of women. However, in the adjusted model, the effect of sibling size
      especially of husband diminishes gradually in the presence of socio-economic
      covariates of the women.

PMID- 28743203
TI  - Biventricular Repair in Interrupted Aortic Arch Type C With Aortic Atresia.
AB  - We report a case of interrupted aortic arch type C with aortic atresia and a
      ventricular septal defect with two well-developed ventricles, who underwent a
      successful single-stage biventricular repair with the modified Yasui procedure
      and arch reconstruction. Angiography done during conduit revision showed
      bilateral brachiocephalic trunks with high branching. The child is doing well six
      years after the initial operation.

PMID- 28743204
TI  - The use of clinical databases in disease outcomes research: Is the ethics of IRB
      review keeping up?
AB  - There is a perceived tension in research ethics between protecting the interests
      of participants and promoting good research as a societal good. The challenge of
      balancing the potential benefits of large clinical databases for disease outcomes
      research while protecting patients' privacy and confidentiality is an example of
      this dynamic. What is new about this tension in the context of "data warehousing"
      is the conflation of many differing interpretations of relevant ethics
      terminology, the proliferation of different kinds of databases, as well as the
      growth of research on a global level without the requisite harmonization of
      regulatory frameworks. The evolution of electronic medical records, the blurring
      of lines between clinical care and research in some rare orphan diseases, the
      growing trend to advocate for patient-centered research, and the advent of "open
      science" to facilitate global research initiatives have also contributed to
      challenging the existing norms for degrees of consent to this kind of research.

PMID- 28743205
TI  - Do baseball pitchers improve mechanics after biomechanical evaluations?
AB  - The purpose of this study was to determine how often flaws in pitching mechanics
      identified from biomechanical analysis are corrected. The biomechanics of 46
      baseball pitchers were evaluated twice, with an average of 12 months (range 2-48
      months) between evaluations. Pitchers were healthy at the time of both
      evaluations, competing at the high school, college, minor league or Major League
      level. After warming up, each participant pitched 10 full-effort fastballs.
      Automated three-dimensional motion analysis was used to compute eight kinematic
      parameters which were compared with a database of elite professional pitchers.
      Flaws-defined as deviations from the elite range-were explained to each
      participant or coach after his initial evaluation. Data from the second
      evaluation revealed that 44% of all flaws had been corrected. Flaws at the
      instant of foot contact (stride length, front foot position, shoulder external
      rotation, shoulder abduction, elbow flexion) or slightly after foot contact (time
      between pelvis rotation and upper trunk rotation) seemed to be corrected more
      often than flaws near the time of ball release (knee extension and shoulder
      abduction). Future research may determine which level athletes or which training
      methods are most effective for correcting flaws.

PMID- 28743206
TI  - Outpatient photodynamic-guided diagnosis of carcinoma in situ with flexible
      cystoscopy: an alternative to conventional inpatient photodynamic-guided bladder
      biopsies in the operating theatre?
AB  - OBJECTIVE: The aim of this prospective open comparative study was to establish
      whether conventional photodynamic-guided bladder biopsies using general
      anaesthesia and rigid resectoscopes (inpatient) can be replaced with less
      traumatic flexible cystoscopy in non-sedated patients (outpatient), without
      compromising the diagnosis of carcinoma in situ (CIS). MATERIALS AND METHODS:
      Thirty-one patients were included. After BCG instillation for CIS, bladder
      biopsies were obtained using photodynamic-guided flexible cystoscopy. Two weeks
      later, patients underwent the conventional inpatient procedure. An external
      pathologist reviewed the biopsy samples. Pain and quality of life (QoL) symptom
      score were recorded. RESULTS: Post-BCG biopsies showed only CIS in 10 patients;
      high-grade Ta or T1 tumour in three patients, who were referred for cystectomy;
      and normal or low-grade tumour tissue in 18 patients. There was a high agreement
      of identification of high-grade disease in biopsies and cytology using the two
      methods (kappa = 0.93, 95% confidence interval 0.8-1.0). The outpatient procedure
      identified four high-grade patients diagnosed as 'normal/low-grade' in the
      inpatient procedure. The opposite was observed in two patients. Quality of
      biopsies did not differ between the two procedures. Pain scores for outpatients
      were low, and median QoL symptom score was significantly lower than for
      inpatients (24 vs 33, p = 0.02). Hospital length of stay was significantly longer
      for inpatients. CONCLUSIONS: Outpatient photodynamic-guided flexible cystoscopy
      is less traumatic than the conventional inpatient procedure in the diagnosis of
      CIS. It is safe and cost-effective, and may be an alternative to conventional
      inpatient biopsy procedures in patients with malignant urine cytology and normal
      white-light cystoscopy.

PMID- 28743207
TI  - Phenylpropanoid 2,3-dioxygenase involved in the cleavage of the ferulic acid side
      chain to form vanillin and glyoxylic acid in Vanilla planifolia.
AB  - Enzyme catalyzing the cleavage of the phenylpropanoid side chain was partially
      purified by ion exchange and gel filtration column chromatography after (NH4)2SO4
      precipitation. Enzyme activities were dependent on the concentration of
      dithiothreitol (DTT) or glutathione (GSH) and activated by addition of 0.5 mM
      Fe2+. Enzyme activity for ferulic acid was as high as for 4-coumaric acid in the
      presence of GSH, suggesting that GSH acts as an endogenous reductant in vanillin
      biosynthesis. Analyses of the enzymatic reaction products with quantitative NMR
      (qNMR) indicated that an amount of glyoxylic acid (GA) proportional to vanillin
      was released from ferulic acid by the enzymatic reaction. These results suggest
      that phenylpropanoid 2,3-dioxygenase is involved in the cleavage of the ferulic
      acid side chain to form vanillin and GA in Vanilla planifolia.

PMID- 28743208
TI  - Bacterial signal transduction networks via connectors and development of the
      inhibitors as alternative antibiotics.
AB  - Bacterial cells possess a signal transduction system that differs from those
      described in higher organisms, including human cells. These so-called two
      component signal transduction systems (TCSs) consist of a sensor (histidine
      kinase, HK) and a response regulator, and are involved in cellular functions,
      such as virulence, drug resistance, biofilm formation, cell wall synthesis, cell
      division. They are conserved in bacteria across all species. Although TCSs are
      often studied and characterized individually, they are assumed to interact with
      each other and form signal transduction networks within the cell. In this review,
      I focus on the formation of TCS networks via connectors. I also explore the
      possibility of using TCS inhibitors, especially HK inhibitors, as alternative
      antimicrobial agents.

PMID- 28743209
TI  - Endoscopic surgery for early-stage nasopharyngeal carcinoma: a justified initial
      option.
AB  - OBJECTIVES: To assess the prognosis of initial endoscopic surgery in T1N0M0 and
      T2N0M0 staged NPC patients. MATERIALS AND METHODS: Between 2002 and 2016, 10
      previously untreated patients with T1N0M0 or T2N0M0 staged NPC volunteered to
      receive endoscopic surgery followed by four courses of TPF chemotherapy. EORTC
      QLQ-C30 and QLQ-H&N35 were used to evaluate the QOL after treatment. RESULTS:
      With the median follow-up of 30 months (range, 9 months to 128 months), the 24
      month survival rate was 100% (6/6), 90% (9/10) patients were still alive and
      well, 20% (2/10) patients reported tumor recurrence. One died of the disease at
      128 months with nasopharyngeal recurrence. Another patient who refused
      preoperative PET-CT had a cervical recurrence at nine months, accepted
      nasopharynx and neck radiation two months later and was still alive and well at
      50 months. In the post-treatment questionnaires, several NPC-specific (pain,
      swallowing, speech, social eating, opening mouth, dry mouth, sticky saliva) QOL
      domains were better preserved compared with radiotherapy alone or combined
      chemoradiotherapy in other surveys. CONCLUSIONS: Initial endoscopic surgery
      combined with chemotherapy maybe justified in the hands of highly experienced
      surgeon in selected early-stage NPC cases and can improve their QOL. In addition,
      preoperative PET-CT should be included in case of possible minimal metastases.

PMID- 28743210
TI  - Fetal middle cerebral artery Doppler in late-term pregnancy: a predicting factor
      for failed induction of labor.
AB  - PURPOSE: To study the role of fetal middle cerebral artery (MCA) Doppler
      evaluated prior to induction of labor in late-term pregnancies, in order to build
      an ultrasound-based predictive model for failed induction. MATERIALS AND METHODS:
      A prospective cohort study on 250 nulliparous women carrying singleton late-term
      pregnancies was conducted. Prior to induction, each patient underwent to an
      ultrasound evaluation for fetal MCA Doppler. Additional ultrasound parameters
      such as cervical length (CL), membranes thickness, amniotic fluid index,
      placental location, and estimated fetal weight (EFW) were collected. According to
      the type of response, women were divided into three groups: (A) responders within
      24 h; (B) responders after 24 h, and (C) no responders. RESULTS: Women who failed
      to enter active labor showed significantly higher fetal MCA pulsatility index
      (PI), longer CL and higher EFW. The estimated probability of logistic regression
      model combining the three variables achieved a sensitivity of 94.2% and a
      specificity of 86.36% (AUC, 0.926; 95% CI, 0.884 - 0.956, p < .0001) using as
      decision probability value the cut off >0.1838. CONCLUSIONS: In late-term
      pregnancies, an ultrasound-based model including cervical length, MCA PI, and EFW
      achieved a good accuracy in predicting those women who are likely to fail
      induction of labor.

PMID- 28743211
TI  - Social context modulates cognitive markers in Obsessive-Compulsive Disorder.
AB  - Error monitoring, cognitive control and motor inhibition control are proposed as
      cognitive alterations disrupted in obsessive-compulsive disorder (OCD). OCD has
      also been associated with an increased sensitivity to social evaluations. The
      effect of a social simulation over electrophysiological indices of cognitive
      alterations in OCD was examined. A case-control cross-sectional study measuring
      event-related potentials (ERP) for error monitoring (Error-Related Negativity),
      cognitive control (N2) and motor control (LRP) was conducted. We analyzed twenty
      OCD patients and twenty control participants. ERP were recorded during a social
      game consisting of a visual discrimination task, which was performed in the
      presence of a simulated superior or an inferior player. Significant social
      effects (different ERP amplitudes in Superior vs. Inferior player conditions)
      were found for OCD patients, but not for controls, in all ERP components.
      Performing the task against a simulated inferior player reduced abnormal ERP
      responses in OCD to levels observed in controls. The hierarchy-induced ERP
      effects were accompanied effects over reaction times in OCD patients. Social
      context modulates signatures of abnormal cognitive functioning in OCD, therefore
      experiencing a social superiority position impacts over cognitive processes in
      OCD such as error monitoring mechanisms. These results open the door for the
      research of new therapeutic choices.

PMID- 28743212
TI  - Caregiver Burden in Parkinson Disease: A Critical Review of Recent Literature.
AB  - Burden is a negative psychological state induced in caregivers by the demands of
      providing care to a person with an illness or a disability. Managing caregiver
      burden in Parkinson disease (PD) is significant because informal caregivers make
      a substantial contribution to the well-being of persons with PD, incurring
      financial, social, and personal losses. Failure to recognize and manage caregiver
      burden may lead to burnout and premature institutionalization of the person with
      PD. We conducted a comprehensive literature review to identify and summarize
      factors that may amplify burden, including motor and nonmotor symptoms of PD,
      caregiver psychiatric symptoms, and caregiver coping style. We review instruments
      designed to sample the construct of burden among caregivers and evaluate
      interventions that may reduce burden, either by directly targeting caregivers or
      by treating PD symptoms associated with burden. We aim to provide a concise
      synopsis of these issues for the clinician or researcher working with this
      population in order to facilitate recognition of caregiver burden, provide
      accurate assessment, administer appropriate interventions, and stimulate further
      research in this area.

PMID- 28743213
TI  - Kallikrein-related peptidase 4 contributes to the tumor metastasis of oral
      squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is a disfiguring malignancy and significantly
      impacts the quality of patient's life. Kallikrein-related peptidase 4 (KLK4),
      which is closely related to cancers, is highly expressed in OSCC. To explore the
      biological function of KLK4 in OSCC, a KLK4-specific shRNA was used to silence
      its endogenous expression, and then the migration and invasion of OSCC cells were
      explored. Results of our study showed that silencing KLK4 inhibited the migration
      and invasion of OSCC cells. The protein levels of epithelial mesenchymal
      transition-associated markers and proteases were also altered by KLK4 silencing.
      Further study showed that the phosphatidylinositol 3-kinase (PI3 K)/protein
      kinase B (AKT) signaling pathway was involved in the function of KLK4. Treatment
      with a PI3 K/AKT activator reversed the migration-inhibitory effect of KLK4
      shRNA. Our study suggests that KLK4 may contribute to the metastasis of OSCC
      through the PI3 K/AKT signaling pathway.

PMID- 28743215
TI  - Fitness band accuracy in older community dwelling adults.
AB  - Fitness bands are widely available and assist with tracking the number of steps
      taken. However, for older people with slow gaits, shorter step widths and/or use
      of ambulatory devices, the accuracy of fitness bands for step counting has not
      been well studied. Using four commercially available fitness bands (Garmin
      Vivofit2TM, Fitbit FlexTM, Up3TM and Microsoft BandTM), we studied 30 older
      people with varying ambulatory abilities. We videotaped participants walking and
      compared the videotaped step count with the fitness band counts. Only 5 of the 30
      participants had accurate readings within a +/-20 percent accuracy for all four
      bands. There was no relationship between the step speed and accuracy of the
      fitness bands. Participants using walkers and walking sticks had none of the
      bands that met the +/-20 percent accuracy. Canes were more variable with
      accuracy. Fitness band manufacturers may need to tune their algorithms for use by
      older people.

PMID- 28743214
TI  - Management of dental patients receiving antiplatelet therapy or chronic oral
      anticoagulation: A review of the latest evidence.
AB  - The perioperative management of patients treated with antithrombotic medications
      who undergo surgical procedures represents a common clinical problem. Dental
      interventions are usually associated with a low risk of bleeding; however, the
      dental implications of new antithrombotic agents are not yet fully understood.
      The present review is based on the latest evidence and recommendations published
      on the periprocedural management of dental patients treated with single or dual
      antiplatelet therapy, vitamin K antagonists, or direct oral anticoagulants for a
      variety of indications.

PMID- 28743216
TI  - Colorectal cancer in the young: a possible role for immune surveillance?
AB  - BACKGROUND: Younger patients with colorectal cancer (CRC) generally have better
      survival in spite of worse clinical and pathological features. METHODS: Twenty
      six patients under 50 years operated for primary CRC were enrolled and matched
      1:2:2 according to stage, tumor site and gender with 52 patients from 50 to 70
      years and 52 patients over 70 years old. RESULTS: Patients under 50 years had a
      significantly longer overall, cancer specific and disease free survival (p =
      .001, p = .007 and p = .05, respectively). However, they had more frequently
      lymphovascular invasion (p = .006) and they more frequently developed
      metachronous CRC at follow-up (p = .03). Nevertheless, preoperative lymphocytes
      blood count/white blood count (LBC/WBC) ratio inversely correlated with age at
      operation (rho = -.21, p = .04) and it predicted CRC recurrence with an accuracy
      of 70%, p < .001 (threshold value LBC/WBC = 0.21%) and better overall, cancer
      specific and disease free survival (p < .0001 for all). At multivariate analysis,
      stage and LBC/WBC ratio resulted independent predictors of disease free survival
      (p = .0001 and p = .01, respectively). CONCLUSIONS: Patients under 50 years had a
      significantly longer survival with a higher LBC/WBC ratio. These results could
      suggest a possible role of immunosurveillance in neoplastic control.

PMID- 28743217
TI  - Identifying content for simulation-based curricula in urology: a national needs
      assessment.
AB  - OBJECTIVE: Simulation-based training is well recognized in the transforming field
      of urological surgery; however, integration into the curriculum is often
      unstructured. Development of simulation-based curricula should follow a stepwise
      approach starting with a needs assessment. This study aimed to identify technical
      procedures in urology that should be included in a simulation-based curriculum
      for residency training. MATERIALS AND METHODS: A national needs assessment was
      performed using the Delphi method involving 56 experts with significant roles in
      the education of urologists. Round 1 identified technical procedures that newly
      qualified urologists should perform. Round 2 included a survey using an
      established needs assessment formula to explore: the frequency of procedures; the
      number of physicians who should be able to perform the procedure; the risk and/or
      discomfort to patients when a procedure is performed by an inexperienced
      physician; and the feasibility of simulation training. Round 3 involved
      elimination and reranking of procedures according to priority. RESULTS: The
      response rates for the three Delphi rounds were 70%, 55% and 67%, respectively.
      The 34 procedures identified in Round 1 were reduced to a final prioritized list
      of 18 technical procedures for simulation-based training. The five procedures
      that reached the highest prioritization were cystoscopy, transrectal ultrasound
      guided biopsy of the prostate, placement of ureteral stent, insertion of urethral
      and suprapubic catheter, and transurethral resection of the bladder. CONCLUSION:
      The prioritized list of technical procedures in urology that were identified as
      highly suitable for simulation can be used as an aid in the planning and
      development of simulation-based training programs.

PMID- 28743218
TI  - Development of a lumbar EMG-based coactivation index for the assessment of
      complex dynamic tasks.
AB  - The objective of this study was to develop and test an EMG-based coactivation
      index and compare it to a coactivation index defined by a biologically assisted
      lumbar spine model to differentiate between tasks. The purpose was to provide a
      universal approach to assess coactivation of a multi-muscle system when a
      computational model is not accessible. The EMG-based index developed utilised
      anthropometric-defined muscle characteristics driven by torso kinematics and EMG.
      Muscles were classified as agonists/antagonists based upon 'simulated' moments of
      the muscles relative to the total 'simulated' moment. Different tasks were used
      to test the range of the index including lifting, pushing and Valsalva. Results
      showed that the EMG-based index was comparable to the index defined by a
      biologically assisted model (r2 = 0.78). Overall, the EMG-based index provides a
      universal, usable method to assess the neuromuscular effort associated with
      coactivation for complex dynamic tasks when the benefit of a biomechanical model
      is not available. Practitioner Summary: A universal coactivation index for the
      lumbar spine was developed to assess complex dynamic tasks. This method was
      validated relative to a model-based index for use when a high-end computational
      model is not available. Its simplicity allows for fewer inputs and usability for
      assessment of task ergonomics and rehabilitation.

PMID- 28743219
TI  - Use of a Thoracic Endograft in an Acute Abdominal Aortic Setting: Case Report and
      Literature Review.
AB  - PURPOSE: We report the case of a thoracic endograft used to achieve exclusion of
      a ruptured proximal paranastomotic abdominal aortic aneurysm (PAAA) as a
      consequence of aortic ballooning. CASE REPORT: A type I proximal endoleak was
      evidenced following endovascular repair of a PAAA with an aortic cuff. The leak
      was treated with ballooning, which caused distal aortic rupture. A thoracic
      endograft was deployed inside the cuff, achieving complete exclusion. At 1 year,
      there are no signs of migration or endoleak with complete PAAA thrombosis,
      according to computed tomographic angiography. CONCLUSION: In hostile proximal
      abdominal aortic neck, challenging anatomies, or urgent cases, the structural
      adaptability of thoracic endografts could provide safe and successful abdominal
      aortic endovascular exclusion.

PMID- 28743220
TI  - Association Between the Visceral Adiposity Index and Homeostatic Model Assessment
      of Insulin Resistance in Participants With Normal Waist Circumference.
AB  - We assessed the correlation between the visceral adiposity index (VAI; a useful
      indicator of adipose distribution and function) and homeostatic model assessment
      of insulin resistance (HOMA-IR) in participants with normal waist circumference.
      A cross-sectional study was conducted, which included 1834 Chinese adults. The
      blood pressure, anthropometric measurements, fasting and postprandial blood
      glucose, fasting insulin, and lipid profiles were measured. The VAI and HOMA-IR
      were calculated. Participants were divided into 4 groups according to the HOMA-IR
      level, and the correlation between the VAI and HOMA-IR was analyzed. The VAI
      gradually increased across the HOMA-IR quartiles ( P < .05), and a Pearson
      correlation analysis showed that VAI was positively related to the HOMA-IR ( P <
      .001) in males and females. After adjusting for the other covariates, VAI was
      independently correlated with the HOMA-IR. A logistic regression analysis
      indicated that VAI elevation was the main risk factor for the increased HOMA-IR
      in both genders. Overall, the VAI was closely correlated with the HOMA-IR in a
      population without central obesity.

PMID- 28743221
TI  - Components of metabolic syndrome and prognosis of renal cell cancer.
AB  - OBJECTIVE: This study analyzes risk associations between metabolic syndrome
      (MetS) components and the extent and prognosis of renal cell cancer (RCC). The
      independent effect of each MetS component is unclear, but they may affect RCC
      prognosis. MATERIALS AND METHODS: The study included 13,873 RCC patients (7720
      men, 6153 women) diagnosed in Finland in 1995-2012. Data on MetS components
      (hypertension, dyslipidemia, diabetes and obesity) were obtained as recorded
      diagnoses or drug purchases related to these conditions. Risk of advanced RCC at
      diagnosis was estimated by logistic regression. Cox proportional hazard
      regression was used to evaluate risk associations for RCC death by MetS
      components after diagnosis. Components were analyzed as time-dependent variables,
      and included in analyses simultaneously to evaluate their independent effects.
      RESULTS: During follow-up (median 1.92, SD 4.35 years) 5179 participants died of
      RCC. Risk of advanced RCC at diagnosis was associated with hypertension [odds
      ratio (OR) 0.82, 95% confidence interval (CI) 0.74-90] and dyslipidemia (OR 0.52,
      95% CI 0.48-0.57). After adjustment for tumor extent, hypertension remained
      associated with increased risk of RCC death (hazard ratio 1.44, 95% CI 1.35
      1.54]. Other MetS components were not independently associated with RCC death
      when taking hypertension into account. Study limitations include the non
      randomized design and lack of smoking status. CONCLUSIONS: The lower risk of
      advanced disease among hypertensive participants may reflect the higher
      proportion of incidental renal tumors found through more frequent physician
      contacts. Nevertheless, hypertension was independently associated with worse RCC
      survival, whereas other MetS components had no clear prognostic role.

PMID- 28743222
TI  - Preparing medical students for the e-patient: Is a theoretical grounding
      required?

PMID- 28743223
TI  - Translation and cultural adaption of the decisions module for colorectal cancer
      screening into a Swedish version - the SCREESCO questionnaire.
AB  - OBJECTIVES: Colorectal cancer (CRC) is suitable for population screening due to
      its high incidence and the recognizable and treatable prephase, and the present
      study is part of the larger study; Screening for Swedish Colons (SCREESCO). In
      Sweden, there is, to our knowledge, no questionnaire assessing shared decision
      making (SDM) with regard to CRC screening and, therefore, the aim of the study
      was to translate and culturally adapt the CRC screening module of the National
      Survey of Medical Decisions (DECISIONS) into a Swedish context. MATERIAL AND
      METHODS: A qualitative design inspired by guidelines based on methods for cross
      cultural adaptation of questionnaires was used. In addition, focus group
      discussions, individual interviews and think-aloud (TA) sessions were performed.
      RESULTS: Of the 54 items included in the original DECISION survey, 32 were
      excluded, 22 were modified, and three were added as a result of the qualitative
      study. How the health care organization communicated and CRC screening knowledge
      was communicated were found to be the most important cultural differences between
      Sweden and the USA. The final questionnaire consists of 24 items. CONCLUSION: The
      process of translation and cultural adaptation of the CRC screening module of the
      DECISIONS survey resulted in the removal and modifying of a considerable number
      of items. The major rationale for the removal and modifying of items can be
      explained by the different cultural traditions between Sweden and the USA when
      communicating with the health care system regarding screening participation and
      how CRC screening information and knowledge is communicated.

PMID- 28743224
TI  - Isolated testicular prostate cancer metastasis.

PMID- 28743225
TI  - Dilemmas in medical ethics in the age of big data.

PMID- 28743226
TI  - Endovascular Therapy Outcomes and Intravascular Ultrasound Findings in
      Thromboangiitis Obliterans (Buerger's Disease).
AB  - PURPOSE: To investigate outcomes of contemporary endovascular therapy and
      intravascular ultrasound (IVUS) findings in thromboangiitis obliterans (TAO)
      patients. METHODS: Between April 2007 and January 2016, 20 patients (mean age
      45+/-8 years; 16 men) underwent endovascular therapy for TAO-related lesions in
      25 consecutive limbs. Subjects exhibited a broad array of clinical symptoms,
      including critical limb ischemia (n=15) and claudication (10) in the lower (n=20)
      and upper (n=5) limbs. RESULTS: Procedure success was achieved in 24 (96%) limbs
      (complete success in 16 and partial success in 8), all of which exhibited
      improvements of at least 1 grade of the Rutherford category. Kaplan-Meier
      analysis showed that reintervention-free rates were 81.9% (95% CI 0.586 to 0.928)
      at 6 months and 71.7% at 10 months (95% CI 0.473 to 0.862). IVUS was performed in
      20 limbs and revealed unique findings, including the "bull's-eye" appearance,
      "lotus-root" appearance, and "bunch of grapes" appearance. During a mean follow
      up of 26+/-19 months, the limb salvage rate was 100% with no deaths. CONCLUSION:
      Contemporary endovascular therapy might be able to serve as a potential option
      for TAO patients with lower and upper limb symptoms. Liberal application of IVUS
      could help us understand the pathology of TAO to support endovascular therapy for
      TAO.

PMID- 28743227
TI  - Suitability of a 7-F ExoSeal Vascular Closure Device for Femoral Artery Punctures
      Made by 8-F or 9-F Introducer Sheaths.
AB  - PURPOSE: To establish the safety and efficacy of the 7-F ExoSeal device for the
      closure of femoral puncture sites made by 8-F or 9-F introducer sheaths. METHODS:
      Between January 2013 and December 2016, 332 patients (mean age 68.4+/-12.1 years;
      195 men) underwent neurointerventional procedures via percutaneous puncture of
      the common femoral artery and an 8-F (n=272, 81.9%) or 9-F (n=60, 18.1%)
      introducer. The access sites were sealed with a 7-F ExoSeal in all cases.
      Procedure success and closure-related complication rates were evaluated, and risk
      factors for complications were analyzed by comparing patient characteristics
      between those who did and did not experience complications. RESULTS: Procedure
      success rates were 99.3% in the 8-F group and 100% in the 9-F group. The overall
      complication rate was 6.3% (n=17; all in the 8-F group), of which 13 (4.8%) were
      minor sequelae, including access-site hematoma (n=8), oozing (n=3),
      pseudoaneurysm (n=1), and retroperitoneal bleeding (n=1). Among the 4 (1.5%)
      major complications were 3 instances of bleeding requiring a blood transfusion
      and 1 surgical vascular repair. No complications were observed in the 9-F group.
      Patients who experienced complications had significantly longer activated
      clotting times (262+/-46 vs 218+/-55 seconds; p<0.001) compared with patients
      without complications. CONCLUSION: A 7-F ExoSeal vascular closure device is safe
      and effective for the closure of femoral puncture sites made by 8-F or 9-F
      introducer sheaths.

PMID- 28743228
TI  - Airway inflammation in chronic obstructive pulmonary disease (COPD): a true
      paradox.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is primarily an airway
      condition, which mainly affects cigarette smokers and presents with shortness of
      breath that is progressive and poorly reversible. In COPD research, there has
      been a long held belief that airway disease progression is due to inflammation.
      Although this may be true in the airway lumen with innate immunity activated by
      the effect of smoke or secondary to infection, the accurate picture of
      inflammatory cells in the airway wall, where the pathophysiological COPD
      remodeling occurs, is uncertain and debatable. Areas covered: The current review
      provides a comprehensive literature survey of the changes in the main
      inflammatory cells in human COPD patients and focuses on contrarian views that
      affect the prevailing dogma on inflammation. The review also delves into the role
      of oxidative stress and inflammasomes in modulating the immune response in COPD.
      Further, the effects of inflammation in affecting the epithelium, fibroblasts,
      and airway remodeling are discussed. Expert commentary: Inflammation as a driving
      force for airway wall damage and remodelling in early COPD is at the very least
      'oversimplified' and is likely to be misleading. This has serious implications
      for rational thinking about the illness, including pathogenesis and designing
      therapy.

PMID- 28743229
TI  - Astilbe thunbergii reduces postprandial hyperglycemia in a type 2 diabetes rat
      model via pancreatic alpha-amylase inhibition by highly condensed procyanidins.
AB  - Type 2 diabetes mellitus (T2DM) is a common global health problem. Prevention of
      this disease is an important task, and functional food supplements are considered
      an effective method. We found potent pancreatic alpha-amylase inhibition in
      Astilbe thunbergii root extract (AT) and confirmed that AT treatment in a T2DM
      rat model reduces post-starch administration blood glucose levels. Activity
      guided isolation revealed procyanidin (AT-P) as the alpha-amylase inhibitory
      component with IC50 = 1.7 MUg/mL against porcine pancreatic alpha-amylase.
      Structure analysis of AT-P revealed it is a B-type procyanidin comprised of four
      types of flavan-3-ols, some with a galloyl group, and catechin attached as the
      terminal unit. The abundant AT-P content and its comparable alpha-amylase
      inhibition to acarbose, the anti-diabetic medicine, suggest that AT is a
      promising food supplement for diabetes prevention.

PMID- 28743230
TI  - CART modulates beta-amyloid metabolism-associated enzymes and attenuates memory
      deficits in APP/PS1 mice.
AB  - INTRODUCTION: Cocaine- and amphetamine-regulated transcript (CART) peptide has
      been demonstrated to exert neuroprotective effects in stroke and some
      neurodegeneration diseases. In current study, we investigated the protective
      effects and underlying mechanisms of CART in APP/PS1 mice. METHODS: The protein
      levels of CART, soluble Abeta1-40 and Abeta1-42 were measured in the hippocampus
      of APP/PS1 mice by enzyme-linked immunosorbent assay. We determined the mRNA and
      protein levels of Abeta metabolism-associated enzymes including neprilysin (NEP),
      insulin-degrading enzyme (IDE), receptor for advanced glycation end products
      (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP-1) in the
      hippocampus of APP/PS1 mice using real-time PCR and western blotting. Spatial
      memory was measured in APP/PS1 mice using the Morris water maze. The
      phosphorylation of AKT, ERK, p38, and JNK was determined using western blotting.
      RESULTS: The levels of soluble Abeta1-40 and Abeta1-42 were significantly
      decreased in the hippocampus of APP/PS1 mice after CART treatment. CART modulated
      the levels of NEP, IDE, RAGE, and LRP-1. In addition, CART inhibited the MAPK
      pathways and activated the AKT pathway, whereas inhibition of the AKT pathway
      decreased the levels of IDE and LRP-1. Furthermore, CART attenuated spatial
      memory deficits in the APP/PS1 mice. CONCLUSION: CART decreases the levels of
      soluble Abeta in the hippocampus of APP/PS1 mice by modulating the expression of
      Abeta metabolism-associated enzymes, which may be associated with the MAPK and
      AKT pathways.

PMID- 28743231
TI  - Genome-wide comparative analysis of putative Pth11-related G protein-coupled
      receptors in fungi belonging to Pezizomycotina.
AB  - BACKGROUND: G-protein coupled receptors (GPCRs) are the largest family of
      transmembrane receptors in fungi, where they play important roles in signal
      transduction. Among them, the Pth11-related GPCRs form a large and divergent
      protein family, and are only found in fungi in Pezizomycotina. However, the
      evolutionary process and potential functions of Pth11-related GPCRs remain
      largely unknown. RESULTS: Twenty genomes of fungi in Pezizomycotina covering
      different nutritional strategies were mined for putative Pth11-related GPCRs.
      Phytopathogens encode much more putative Pth11-related GPCRs than symbionts,
      saprophytes, or entomopathogens. Based on the phylogenetic tree, these GPCRs can
      be divided into nine clades, with each clade containing fungi in different
      taxonomic orders. Instead of fungi from the same order, those fungi with similar
      nutritional strategies were inclined to share orthologs of putative Pth11-related
      GPCRs. Most of the CFEM domain-containing Pth11-related GPCRs, which were only
      included in two clades, were detected in phytopathogens. Furthermore, many
      putative Pth11-related GPCR genes of phytopathogens were upregulated during
      invasive plant infection, but downregulated under biotic stress. The expressions
      of putative Pth11-related GPCR genes of saprophytes and entomopathogens could be
      affected by nutrient conditions, especially the carbon source. The gene
      expressions revealed that Pth11-related GPCRs could respond to biotic/abiotic
      stress and invasive plant infection with different expression patterns.
      CONCLUSION: Our results indicated that the Pth11-related GPCRs existed before the
      diversification of Pezizomycotina and have been gained and/or lost several times
      during the evolutionary process. Tandem duplications and trophic variations have
      been important factors in this evolution.

PMID- 28743232
TI  - Emergency medical service provider decision-making in out of hospital cardiac
      arrest: an exploratory study.
AB  - BACKGROUND: There are approximately 60,000 out-of-hospital cardiac arrests (OHCA)
      in the United Kingdom (UK) each year. Within the UK there are well-established
      clinical practice guidelines that define when resuscitation should be commenced
      in OHCA, and when resuscitation should cease. Background literature indicates
      that decision-making in the commencement and cessation of resuscitation efforts
      in OHCA is complex, and not comprehensively understood. No relevant research from
      the UK has been published to date and this research study seeks to explore the
      influences on UK Emergency Medical Service (EMS) provider decision-making when
      commencing and ceasing resuscitation attempts in OHCA. The aim of this research
      to explore the influences on UK Emergency Medical Services provider decision
      making when commencing and ceasing resuscitation attempts in OHCA. METHODS: Four
      focus groups were convened with 16 clinically active EMS providers. Four case
      vignettes were discussed to explore decision-making within the focus groups.
      Thematic analysis was used to analyse transcripts. RESULTS: This research found
      that there are three stages in the decision-making process when EMS providers
      consider whether to commence or cease resuscitation attempts in OHCA. These
      stages are: the call; arrival on scene; the protocol. Influential factors present
      at each of the three stages can lead to different decisions and variability in
      practice. These influences are: factual information available to the EMS
      provider; structural factors such as protocol, guidance and research; cultural
      beliefs and values; interpersonal factors; risk factors; personal values and
      beliefs. CONCLUSIONS: An improved understanding of the circumstantial, individual
      and interpersonal factors that mediate the decision-making process in clinical
      practice could inform the development of more effective clinical guidelines,
      education and clinical decision support in OHCA. These changes have the potential
      to lead to greater consistency. and EMS provider confidence, with the potential
      for improved patient outcome from OHCA.

PMID- 28743233
TI  - Erratum to: Conserved gene expression in sperm reservoirs between birds and
      mammals in response to mating.

PMID- 28743234
TI  - A cross-sectional sero-survey on preoperative HBV vaccination policy in Poland.
AB  - BACKGROUND: A two-dose preoperative vaccination schedule against HBV has been the
      widely accepted policy in Poland. However, its effectiveness has not yet been
      assessed. OBJECTIVE: To evaluate a two-dose preoperative HBV vaccination policy
      by an assessment of the proportion of patients who don't present a protective
      level of anti-HBs (<10.0 mIU/ml). METHODS: Consecutive patients from
      surgical/gynecologic wards of 12 randomly selected hospitals in West Pomerania,
      Poland, hospitalized between 2010 and 2013, vaccinated against HBV with a two
      dose regimen, were asked to complete an anonymous questionnaire. Serum samples
      were assayed for anti-HBs with the use of third-generation testing methods. To
      compare sensitivity versus specificity across a range of values for the ability
      to predict a dichotomous outcome (a protection against HBV infection) a Receiver
      operating characteristic (ROC) curve was determined. RESULTS: There were 193
      patients, 58.5% women, median age 52 years. Almost a half (46.0%) of the patients
      were operated on within 0-60 days of taking the second vaccine dose, 16.2% - 61
      180 days after, 37.8% >180 days after. Anti-HBs titer was below a protective
      level in 49.2% of participants (0.0 mIU/ml in 17.8%, 0.1-9.9 mIU/ml in 31.4%);
      none of them were aware of this fact. Age <= 52 years (OR = 1.89) and having
      surgery more than 37.5 days after HBV vaccination (OR = 2.70) were associated
      with greater odds of being protected against HBV infection through vaccination.
      For the time frame between the second dose implementation and surgery 23 days, a
      sensitivity of 84% and specificity of 22% for obtaining protection against HBV
      infection was found, for the time frame >37.5 days - sensitivity remained high
      (80%), while specificity increased (41%); there was an apparent peek on the ROC
      curve between 38 and 60 day. In the group vaccinated 0-37.5 days before surgery,
      less patients had the protective level of anti-HBs titer than in vaccinated 38-60
      days before surgery (32.3% vs 60.0%; p = 0.03). CONCLUSIONS: The success rate in
      achieving adequate immune protection with two dose HBV vaccination schedule in
      preoperatively vaccinated patients is relatively low, especially among those
      vaccinated less than five weeks prior to surgery. In more than a third of cases
      the standard three-dose regimen could have been implemented, as participants had
      time to complete a third dose. Current recommendations regarding a preoperative
      policy with a 2-dose vaccination schedule in Poland should be revised; the best
      time to perform surgery after the implementation of the second dose of vaccine in
      the context of patient protection against HBV infection would be between 38 and
      60 days.

PMID- 28743235
TI  - Magnetic hyperthermia enhance the treatment efficacy of peri-implant
      osteomyelitis.
AB  - BACKGROUND: When bacteria colony persist within a biofilm, suitable drugs are not
      yet available for the eradication of biofilm-producing bacteria. The aim of this
      study is to study the effect of magnetic nano-particles-induced hyperthermia on
      destroying biofilm and promoting bactericidal effects of antibiotics in the
      treatment of osteomyelitis. METHODS: Sixty 12-weeks-old male Wistar rats were
      used. A metallic 18G needle was implanted into the bone marrow cavity of distal
      femur after the injection of Methicillin-sensitive Staphylococcus aureus (MSSA).
      All animals were divided into 5 different treatment modalities. The
      microbiological evaluation, scanning electron microscope examination,
      radiographic examination and then micro-CT evaluation of peri-implant bone
      resorption were analyzed. RESULTS: The pathomorphological characteristics of
      biofilm formation were completed after 40-days induction of osteomyelitis. The
      inserted implants can be heated upto 75  degrees C by magnetic heating without
      any significant thermal damage on the surrounding tissue. We also demonstrated
      that systemic administration of vancomycin [VC (i.m.)] could not eradicate the
      bacteria; but, local administration of vancomycin into the femoral canal and the
      presence of magnetic nanoparticles hyperthermia did enhance the eradication of
      bacteria in a biofilm-based colony. In these two groups, the percent bone volume
      (BV/TV: %) was significantly higher than that of the positive control.
      CONCLUSIONS: For the treatment of chronic osteomyelitis, we developed a new
      modality to improve antibiotic efficacy; the protection effect of biofilms on
      bacteria could be destroyed by magnetic nanoparticles-induced hyperthermia and
      therapeutic effect of systemic antibiotics could be enhanced.

PMID- 28743236
TI  - Assessing the adequacy of lymph node yield for different tumor stages of colon
      cancer by nodal staging scores.
AB  - BACKGROUND: According to the current official guidelines, at least 12 lymph nodes
      (LNs) are qualified as an adequate sampling for colon cancer patients. However,
      patients evaluated with less nodes were still common in the United States, and
      the prevalence of positive nodal disease may be under-estimated because of the
      false-negative assessment. In this study, we present a statistical model that
      allows preoperative determination of the minimum number of lymph nodes needed to
      confirm a node-negative disease with certain confidence. METHODS: Adenocarcinoma
      colon cancer patients with stage T1-T3, diagnosed between 2004 and 2013, who did
      not receive neoadjuvant therapies and had at least one lymph node pathologically
      examined, were extracted from the Surveillance, Epidemiology and End Results
      (SEER) database. A beta binomial distribution was used to estimate the
      probability of an occult nodal disease is truly node-negative as a function of
      total number of LNs examined and T stage. RESULTS: A total of 125,306 patients
      met study criteria; and 47,788 of those were node-positive. The probability of
      falsely identifying a patient as node-negative decreased with an increasing
      number of nodes examined for each stage, and was estimated to be 72% for T1 and
      T2 patients with a single node examined and 57% for T3 patients with a single
      node examined. To confirm an occult nodal disease with 90% confidence, 3, 8, and
      24 nodes need to be examined for patients from stage T1, T2, and T3,
      respectively. CONCLUSIONS: The false-negative rate of diagnosed node negative,
      together with the minimum number of examined nodes for adequate staging, depend
      preoperatively on the clinical T stage. Predictive tools can recommend a
      threshold on the minimum number of examined nodes regarding to the favored level
      of confidence for each T stage.

PMID- 28743237
TI  - Gender differences in characteristics of physical and sexual victimization in
      patients with dual diagnosis: a cross-sectional study.
AB  - BACKGROUND: Patients with substance use disorders and co-occurring mental health
      disorders are vulnerable to violent victimization. However, no evidence-based
      interventions are available to reduce patients' vulnerability. An exploration of
      the characteristics of physical and sexual violence can provide valuable
      information to support the development of interventions for these patients. This
      study aimed to examine gender differences in characteristics of violent
      victimization in patients with dual diagnosis. METHODS: In this cross-sectional
      survey study recent incidents of physical and sexual assault were examined with
      the Safety Monitor in 243 patients with dual diagnosis. Chi-square tests were
      used to examine gender differences in the prevalence of physical and sexual
      victimization. Fisher's exact tests and Fisher-Freeman-Halton exact tests were
      used to determine whether there were significant differences between victimized
      men and women with regard to perpetrators, locations, reporting to the police and
      speaking about the assault with others. RESULTS: There was no significant
      difference in the prevalence of physical violence in men (35%) and women (47%)
      with dual diagnosis. There was a significant association between gender of the
      victim and type of perpetrator (P < .001). Men were most often physically abused
      by a stranger or an acquaintance, whereas women were most frequently abused by an
      (ex)partner. Sexual violence was more prevalent in women (29%) compared to men
      (4%) (P < .001). Patients with dual diagnosis were unlikely to report incidents
      of physical abuse and sexual assault to the police and to speak about it with
      caregivers. CONCLUSIONS: Characteristics of physical violence are different for
      men and women with dual diagnosis. Women with dual diagnosis are more often
      victims of sexual violence compared to men. Interventions aimed at reducing
      patients' vulnerability for victimization should take gender differences into
      account.

PMID- 28743238
TI  - Determinants of stunting and severe stunting among Burundian children aged 6-23
      months: evidence from a national cross-sectional household survey, 2014.
AB  - BACKGROUND: Burundi is one of the poorest countries and is among the four
      countries with the highest prevalence of stunting (58%) among children aged less
      than 5 years. This situation undermines the economic growth of the country as
      undernutrition is strongly associated with less schooling and reduced economic
      productivity. Identifying the determinants of stunting and severe stunting may
      help policy-makers to direct the limited Burundian resources to the most
      vulnerable segments of the population, and thus make it more cost effective. This
      study aimed to identify predictors of stunting and severe stunting among children
      aged less than two years in Burundi. METHODS: The sample is made up of 6199
      children aged 6 to 23 months with complete anthropometric measurements from the
      baseline survey of an impact evaluation study of the Performance-Based financing
      (PBF) scheme applied to nutrition services in Burundi from 2015 to 2017. Binary
      and multivariable logistic regression analyses were used to examine stunting and
      severe stunting against a set of child, parental and household variables such as
      child's age or breastfeeding pattern, mother's age or knowledge of malnutrition,
      household size or socio-economic status. RESULTS: The prevalence of stunting and
      severe stunting were 53% [95%CI: 51.8-54.3] and 20.9% [95%CI: 19.9-22.0]
      respectively. Compared to children from 6-11 months, children of 12-17 months and
      18-23 months had a higher risk of stunting (AdjOR:2.1; 95% CI: 1.8-2.4 and 3.2;
      95% CI: 2.8-3.7). Other predictors for stunting were small babies (AdjOR=1.5; 95%
      CI: 1.3-1.7 for medium-size babies at birth and AdjOR=2.9; 95% CI: 2.4-3.6 for
      small-size babies at birth) and male children (AdjOR=1.5, 95% CI: 1.4-1.8). In
      addition, having no education for mothers (AdjOR=1.6; 95% CI: 1.2-2.1), incorrect
      mothers' child nutrition status assessment (AdjOR=3.3; 95% CI: 2.8-4), delivering
      at home (AdjOR=1.4; 95% CI: 1.2-1.6) were found to be predictors for stunting.
      More than to 2 under five children in the household (AdjOR=1.45; 95% CI: 1.1-1.9
      for stunting and AdjOR= 1.5; 95% CI: 1.2-1.9 for severe stunting) and wealth were
      found to be predictors for both stunting and severe stunting. The factors
      associated with stunting were found to be applicable for severe stunting as well.
      CONCLUSION: Mother's education level, mother's knowledge about child nutrition
      status assessment and health facility delivery were predictors of child stunting.
      Our study confirms that stunting and severe stunting is in Burundi, as elsewhere,
      a multi-sectorial problem. Some determinants relate to the general development of
      Burundi: education of girls, poverty, and food security; will be addressed by a
      large array of actions. Some others relate to the health sector and its
      performance - we think in particular of the number of children under five in the
      household (birth spacing), the relationship with the health center and the
      knowledge of the mother on malnutrition. Our findings confirm that the Ministry
      of Health and its partners should strive for better performing and holistic
      nutrition services: they can contribute to better nutrition outcomes.

PMID- 28743239
TI  - Acid tolerance properties of dental biofilms in vivo.
AB  - BACKGROUND: The ecological plaque hypothesis explains caries development as the
      result of the enrichment of acid tolerant bacteria in dental biofilms in response
      to prolonged periods of low pH. Acid production by an acid tolerant microflora
      causes demineralisation of tooth enamel and thus, individuals with a greater
      proportion of acid tolerant bacteria would be expected to be more prone to caries
      development. Biofilm acid tolerance could therefore be a possible biomarker for
      caries prediction. However, little is known about the stability of biofilm acid
      tolerance over time in vivo or the distribution throughout the oral cavity.
      Therefore the aim of this study was to assess intra-individual differences in
      biofilm acid-tolerance between different tooth surfaces and inter-individual
      variation as well as stability of acid tolerance over time. RESULTS: The majority
      of the adolescents showed low scores for biofilm acid tolerance. In 14 of 20
      individuals no differences were seen between the three tooth sites examined. In
      the remaining six, acid-tolerance at the premolar site differed from one of the
      other sites. At 51 of 60 tooth sites, acid-tolerance at baseline was unchanged
      after 1 month. However, acid tolerance values changed over a 1-year period in 50%
      of the individuals. CONCLUSIONS: Biofilm acid tolerance showed short-term
      stability and low variation between different sites in the same individual
      suggesting that the acid tolerance could be a promising biological biomarker
      candidate for caries prediction. Further evaluation is however needed and
      prospective clinical trials are called for to evaluate the diagnostic accuracy.

PMID- 28743240
TI  - Whole brain radiotherapy versus stereotactic radiosurgery for 4-10 brain
      metastases: a phase III randomised multicentre trial.
AB  - BACKGROUND: Maintenance of quality of life is the primary goal during treatment
      of brain metastases (BM). This is a protocol of an ongoing phase III randomised
      multicentre study. This study aims to determine the exact additional palliative
      value of stereotactic radiosurgery (SRS) over whole brain radiotherapy (WBRT) in
      patients with 4-10 BM. METHODS: The study will include patients with 4-10 BM from
      solid primary tumours diagnosed on a high-resolution contrast-enhanced MRI scan
      with a maximum lesional diameter of 2.5 cm in any direction and a maximum
      cumulative lesional volume of 30 cm3. Patients will be randomised between WBRT in
      five fractions of 4 Gy to a total dose of 20 Gy (standard arm) and single dose
      SRS to the BMs (study arm) in the range of 15-24 Gy. The largest BM or a
      localisation in the brainstem will determine the prescribed SRS dose. The primary
      endpoint is difference in quality of life (EQ5D EUROQOL score) at 3 months after
      radiotherapy with regard to baseline. Secondary endpoints are difference in
      quality of life (EQ5D EUROQOL questionnaire) at 6, 9 and 12 months after
      radiotherapy with regard to baseline. Other secondary endpoints are at 3, 6, 9
      and 12 months after radiotherapy survival, Karnofsky >= 70, WHO performance
      status, steroid use (mg), toxicity according to CTCAE V4.0 including hair loss,
      fatigue, brain salvage during follow-up, type of salvage, time to salvage after
      randomisation and Barthel index. Facultative secondary endpoints are
      neurocognition with the Hopkins verbal learning test revised, quality of life
      EORTC QLQ-C30, quality of life EORTC BN20 brain module and fatigue scale EORTC
      QLQ-FA13. DISCUSSION: Worldwide, most patients with more than 4 BM will be
      treated with WBRT. Considering the potential advantages of SRS over WBRT, i.e.
      limiting radiation doses to uninvolved brain and a high rate of local tumour
      control by just a single treatment with fewer side effects, such as hair loss and
      fatigue, compared to WBRT, SRS might be a suitable alternative for patients with
      4-10 BM. TRIAL REGISTRATION: Trial registration number: NCT02353000 , trial
      registration date 15th January 2015, open for accrual 1st July 2016, nine
      patients were enrolled in this trial on 14th April 2017.

PMID- 28743241
TI  - Complete ophthalmoplegia, complete ptosis and dilated pupil due to internal
      carotid artery dissection: as the first manifestation of Takayasu arteritis.
AB  - BACKGROUND: Takayasu arteritis is a rare, chronic large vessel vasculitis
      involving the aorta and its primary branches. As the disease progresses, the
      active inflammation of large vessels leads to dilation, narrowing and occlusion
      of the arteries. Arterial dissection is due to separation of the layers of the
      arterial wall resulting in a false lumen, where blood seeps into the vessel wall.
      Neurological sequelae of intracranial arterial dissection results from cerebral
      ischemia due to thromboembolism and hypo perfusion. Internal carotid artery
      dissection in Takayasu arteritis is very rare and complete ophthalmoplegia due to
      internal carotid artery dissection is also rare. This is the first case report of
      Takayasu arteritis presenting as complete ophthalmoplegia due to internal carotid
      artery dissection. CASE PRESENTATION: A 38-year-old Sri Lankan female presented
      with sudden onset severe headache, fixed dilated pupil, complete ptosis and
      ophthalmoplegia on the right side. On imaging, dissection and dilatation was
      evident in the right internal carotid artery from the origin up to the cavernous
      segment. She also had stenosis and aneurysmal dilatation of right subclavian
      artery. Takayasu arteritis was diagnosed subsequently. She was started on aspirin
      and high dose steroids. CONCLUSIONS: Internal carotid artery dissection within
      the cavernous sinus can lead to third, fourth and sixth nerve palsy due to
      compression, stretching and ischemia from occlusion of the nutritional arteries.
      This case report illustrates that internal carotid artery dissection should be a
      differential diagnosis in palsies of the third, fourth, or sixth cranial nerves,
      especially when associated with headache. In cases of internal carotid artery
      dissection, vasculitis such as Takayasu arteritis should also be considered.

PMID- 28743242
TI  - Association between the XRCC1 polymorphisms and clinical outcomes of advanced
      NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the
      PRISMA statement.
AB  - BACKGROUND: Base excision repair (BER) pathway is a DNA repair pathway that is
      important in carcinogenesis and in response to DNA-damaging chemotherapy. XRCC1
      is one of important molecular markers for BER. So far, the role of XRCC1
      polymorphisms with clinical outcomes of advanced NSCLC treated with platinum
      based chemotherapy is inconclusive. To explore the relationship between XRCC1
      polymorphisms and platinum-based chemotherapy in advanced NSCLC patients, we
      performed this meta-analysis. METHODS: Crude odds ratios (ORs), Cox proportional
      hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were
      adopted to assess the strength of association between XRCC1 polymorphisms and
      response rate, Overall survival (OS) and progression free survival (PFS) of
      advanced NSCLC treated with platinum-based chemotherapy. Q test and I 2 test were
      used for the assessment of heterogeneity. Subgroup analyses were conducted when
      heterogeneity exists. Begg's funnel plots and Egger's linear regression test were
      used to estimate publication bias. Sensitivity analysis was performed to evaluate
      the stability of the result. RESULTS: A total of 19 studies including 2815
      individuals were eligible for the analysis, results showed XRCC1 194Arg allele
      was negatively associated with the objective response rate relative to 194Trp,
      and results of homozygous model, dominant model and heterozygous model suggested
      a gene dosage effect negative correlation between 194Arg allele and objective
      response rate(ArgArg vs TrpTrp: OR = 0.64(95%CI: 0.44-0.91); ArgArg + TrpArg vs
      TrpTrp: OR = 0.79(95%CI: 0.57-1.11); TrpArg vs TrpTrp: OR = 1.05(95%CI: 0.73
      1.51)). XRCC1 399Gln may indicate favorable overall survival (GlnGln + GlnArg vs
      ArgArg: HR = 0.65(95%CI: 0.43-0.98)) and favorable PFS (GlnGln vs ArgArg: HR =
      0.72(95%CI: 0.48-0.97)) in Asian patients; while in Caucasian patients, XRCC1
      399Gln indicated poorer overall survival (GlnGln vs ArgArg: HR = 2.29(95%CI: 1.25
      3.33)). CONCLUSIONS: Our results indicated that in NSCLC patients treated with
      platinum-based regimen, XRCC1 194Arg allele suggest poor objective response rate,
      the GlnGln genotype of XRCC1 399 suggest poorer overall survival in Caucasian
      patients, and longer PFS in Asian patients.

PMID- 28743243
TI  - The MalR type regulator AcrC is a transcriptional repressor of acarbose
      biosynthetic genes in Actinoplanes sp. SE50/110.
AB  - BACKGROUND: Acarbose is used in the treatment of diabetes mellitus type II and is
      produced by Actinoplanes sp. SE50/110. Although the biosynthesis of acarbose has
      been intensively studied, profound knowledge about transcription factors involved
      in acarbose biosynthesis and their binding sites has been missing until now. In
      contrast to acarbose biosynthetic gene clusters in Streptomyces spp., the
      corresponding gene cluster of Actinoplanes sp. SE50/110 lacks genes for
      transcriptional regulators. RESULTS: The acarbose regulator C (AcrC) was
      identified through an in silico approach by aligning the LacI family regulators
      of acarbose biosynthetic gene clusters in Streptomyces spp. with the Actinoplanes
      sp. SE50/110 genome. The gene for acrC, located in a head-to-head arrangement
      with the maltose/maltodextrin ABC transporter malEFG operon, was deleted by
      introducing PCR targeting for Actinoplanes sp. SE50/110. Characterization was
      carried out through cultivation experiments, genome-wide microarray
      hybridizations, and RT-qPCR as well as electrophoretic mobility shift assays for
      the elucidation of binding motifs. The results show that AcrC binds to the
      intergenic region between acbE and acbD in Actinoplanes sp. SE50/110 and acts as
      a transcriptional repressor on these genes. The transcriptomic profile of the
      wild type was reconstituted through a complementation of the deleted acrC gene.
      Additionally, regulatory sequence motifs for the binding of AcrC were identified
      in the intergenic region of acbE and acbD. It was shown that AcrC expression
      influences acarbose formation in the early growth phase. Interestingly, AcrC does
      not regulate the malEFG operon. CONCLUSIONS: This study characterizes the first
      known transcription factor of the acarbose biosynthetic gene cluster in
      Actinoplanes sp. SE50/110. It therefore represents an important step for
      understanding the regulatory network of this organism. Based on this work,
      rational strain design for improving the biotechnological production of acarbose
      can now be implemented.

PMID- 28743244
TI  - Non-adherence to medication regimens among older African-American adults.
AB  - BACKGROUND: Despite concerns about racial differences on adherence to prescribed
      medication rigimens among older adults, current information about nonadherence
      among underserved elderly African Americans with co-morbidities is limited. This
      study examines the association between adherence to drug regimens and an array of
      medication-related factors, including polypharmacy, medication regimen
      complexity, use of Potentially Inappropriate Medications (PIM), and knowledge
      about the therapeutic purpose and instructions of medication use. METHODS: Four
      hundred African Americans, aged 65 years and older, were recruited from South Los
      Angeles. Structured, face-to-face interviews and visual inspection of
      participants' medications were conducted. From the medication container labels,
      information including strength of the drug, expiration date, instructions, and
      special warnings were recorded. The Medication Regimen Complexity Index (MRCI)
      was measured to quantify multiple features of drug regimen complexity. The Beers
      Criteria was used to measure the PIM use. RESULTS: Participants reported taking
      an average of 5.7 prescription drugs. Over 56% could not identify the purpose of
      at least one of their medications. Only two-thirds knew dosage regimen of their
      medications. Thirty-five percent of participants indicated that they purposely
      had skipped taking at least one of their medications within last three days. Only
      8% of participants admitted that they forgot to take their medications. The
      results of multivariate analysis showed that co-payment for drugs, memory
      deficits, MRCI, and medication-related knowledge were all associated with
      adherence to dosage regimen of medications. Participants with a higher level of
      knowledge about therapeutic purpose and knowledge about dosage regimen of their
      medications were seven times (CI: 4.2-10.8) more likely to adhere to frequency
      and dose of medications. Participants with a low complexity index were two times
      (CI: 1.1-3.9) more likely to adhere to the dosage regimen of their medications,
      compared with participants with high drug regimen complexity index. CONCLUSIONS:
      While other studies have documented that non-adherence remains an important issue
      among older adults, our study shows that for underserved elderly African
      Americans, these issues are particularly striking. A periodic comprehensive
      assessment of all medications that they use remains a critical initial step to
      identify medication related issues. Assessment of their disease and medication
      related knowledge (e.g., therapeutic purposes, side-effects, special
      instructions, etc.) and their ability to follow complicated medication regimens
      and modification of their drug regimens requires inter-professional
      collaboration.

PMID- 28743245
TI  - Mortality trends for ischemic heart disease in China: an analysis of 102
      continuous disease surveillance points from 1991 to 2009.
AB  - BACKGROUND: In the past 20 years, the trends of ischemic heart disease (IHD)
      mortality in China have been described in divergent claims. This research
      analyzes mortality trends for IHD by using the data from 102 continuous Disease
      Surveillance Points (DSP) from 1991 to 2009. METHOD: The 102 continuous DSP
      covered 7.3 million people during the period 1991-2000, and then were expanded to
      a population of 52 million in the same areas for 2004-2009. The data were
      adjusted by using garbage code redistribution and underreporting rate, mapped
      from international classification of diseases ICD-9 to ICD-10. The mortality
      rates for IHD were further adjusted by the crude death proportion multiplied by
      the total number of deaths in the mortality envelope, which was calculated by
      using logrt = a + bt. Age-standard death rates (ASDRs) were computed using
      China's 2010 census population structure. Trend in IHD was calculated from ASDRs
      by using a joinpoint regression model. RESULTS: The IHD ASDRs increased in total
      in regions with an average annual percentage change (AAPC) 4.96%, especially for
      the Southwest (AAPC = 7.97%) and Northeast areas (AAPC = 7.10%), and for male and
      female subjects (with 5% AAPC) as well. In rural areas, the year 2000 was a cut
      off point for mortality rate with annual percentage change increasing from 3.52%
      in 1991-2000 to 9.02% in 2000-2009, which was much higher than in urban areas
      (AAPC = 1.05%). And the proportion of deaths increased in older adults, and more
      male deaths occurred before age 60 compared to female deaths. CONCLUSION: By
      observing a wide range of areas across China from 1991 to 2009, this paper
      concludes that the ASDR trend for IHD increased. These trends reflect changes in
      the Chinese standard of living and lifestyle with diets higher in fat, higher
      blood lipids and increased body weight.

PMID- 28743246
TI  - Associations between national viral hepatitis policies/programmes and country
      level socioeconomic factors: a sub-analysis of data from the 2013 WHO viral
      hepatitis policy report.
AB  - BACKGROUND: As more countries worldwide develop national viral hepatitis
      strategies, it is important to ask whether context-specific factors affect their
      decision-making. This study aimed to determine whether country-level
      socioeconomic factors are associated with viral hepatitis programmes and policy
      responses across WHO Member States (MS). METHODS: WHO MS focal points completed a
      questionnaire on national viral hepatitis policies. This secondary analysis of
      data reported in the 2013 Global Policy Report on the Prevention and Control of
      Viral Hepatitis in WHO Member States used logistic regression to examine
      associations between four survey questions and four socioeconomic factors:
      country income level, Human Development Index (HDI), health expenditure and
      physician density. RESULTS: This analysis included 119 MS. MS were more likely to
      have routine viral hepatitis surveillance and to have a national strategy and/or
      policy/guidelines for preventing infection in healthcare settings if they were in
      the higher binary categories for income level, HDI, health expenditure and
      physician density. In multivariable analyses, the only significant finding was a
      positive association between having routine surveillance and being in the higher
      binary HDI category (adjusted odds ratio 26; 95% confidence interval 2.0-340).
      CONCLUSION: Countries with differing socioeconomic status indicators did not
      appear to differ greatly regarding the existence of key national policies and
      programmes. A more nuanced understanding of the multifaceted interactions of
      socioeconomic factors, health policy, service delivery and health outcomes is
      needed to support country-level efforts to eliminate viral hepatitis.

PMID- 28743247
TI  - A randomized phase II study of paclitaxel alone versus paclitaxel plus sorafenib
      in second- and third-line treatment of patients with HER2-negative metastatic
      breast cancer (PASO).
AB  - BACKGROUND: We conducted an open-label, randomized, two-arm multi-center study to
      assess the efficacy and safety of paclitaxel versus paclitaxel + sorafenib in
      patients with locally advanced or metastatic HER2-negative breast cancer.
      METHODS: Patients were randomly assigned to receive either paclitaxel monotherapy
      (80 mg/m2) weekly (3 weeks on, 1 week off) plus sorafenib 400 mg orally, twice a
      day taken continuously throughout 28 day cycles. Sorafenib dose was gradually
      escalated from a starting dose of 200 mg twice a day. The primary endpoint was
      progression free survival (PFS). RESULTS: A pre-planned efficacy interim analysis
      was performed on the data of 60 patients, 30 patients in each treatment arm.
      Median PFS was estimated at 6.6 months (95% CI: 5.1 to 9.0) in patients
      randomized to single-agent paclitaxel (Arm A) and 5.6 months (95% CI: 3.8 to 6.5)
      in patients randomized to paclitaxel-sorafenib combination (Arm B) therapy.
      Contrary to the hypothesis, the treatment effect was statistically significant in
      favor of paclitaxel monotherapy (hazard ratio 1.80, 95% CI: 1.02 to 3.20; log
      rank test P = 0.0409). It was decided to stop the trial early for futility.
      Median OS was also in favor of Arm A (20.7 months (95% CI: 16.4 to 26.7) versus
      12.1 months (95% CI: 5.8 to 20.4) in Arm B. Clinical control was achieved in 28
      patients (93.3%) in Arm A and in 21 patients 70.0% in Arm B. Overall response
      rate was met in 43.3% of patients in Arm A and in 40.0% in Arm B. Toxicities were
      increased in Arm B with higher rates of diarrhea, nausea, neutropenia, hand-foot
      skin reaction (HFSR) and anorexia, Grad 3 and 4 toxicities were rare.
      CONCLUSIONS: In this pre-planned interim analysis, paclitaxel-sorafenib
      combination therapy was not found to be superior to paclitaxel monotherapy with
      regard to the primary end point, progression-free survival. The trial was
      therefore discontinued early. There was no indication of more favorable outcomes
      for combination therapy in secondary efficacy end points. As expected, the safety
      and toxicity profile of the combination therapy was less favorable compared to
      monotherapy. Overall, this trial did not demonstrate that adding sorafenib to
      second- or third-line paclitaxel provides any clinical benefit to patients with
      HER2-negative advanced or metastatic breast cancer. Cautious dosing using a
      sorafenib ramp up schedule might have contributed to negative results. TRIAL
      REGISTRATION: The study was registered at EudraCT (No 2009-018025-73) and
      retrospectively registered at Clinical trials.gov on March 17, 2011 ( NCT01320111
      ).

PMID- 28743248
TI  - Immunological recovery in tuberculosis/HIV co-infected patients on antiretroviral
      therapy: implication for tuberculosis preventive therapy.
AB  - BACKGROUND: Understanding the immune response to combination antiretroviral
      therapy (cART) is essential for a clear approach to tuberculosis (TB) preventive
      therapy. We investigated the immunological recovery in cART-treated HIV-infected
      patients developing TB compared to those who remained free of TB. METHODS: We
      extracted data of HIV-infected patients from a multicenter cohort for the HIV
      clinical surveillance in Germany. No patients included in our study had TB at the
      beginning of the observation. Using a longitudinal mixed model, we assessed the
      differences in the mean change of biomarkers (CD4+ cell count, CD8+ cell count,
      CD4:CD8 ratio and viral load) since cART initiation in patients who remained free
      of TB vs. those developing TB. To detect the best-fit trajectories of the
      immunological biomarkers, we applied a multivariable fractional polynomials
      model. RESULTS: We analyzed a total of 10,671 HIV-infected patients including 139
      patients who developed TB during follow-up. The highest TB incidences were
      observed during the first two years since cART initiation (0.32 and 0.50 per 100
      person-years). In an adjusted multivariable mixed model, we found that the
      average change in CD4+ cell count recovery was significantly greater by 33
      cells/MUl in patients who remained free of TB compared with those developing TB.
      After the initial three months of cART, 65.6% of patients who remaining free of
      TB achieved CD4+ count of >=400 cells/MUl, while only 11.3% of patients
      developing TB reached this immunological status after the three months of cART.
      We found no differences in the average change of CD8+ cell count, CD4:CD8 ratio
      or viral load between the two-patient groups. CONCLUSION: All HIV-infected
      patients responded to cART. However, patients developing TB showed reduced
      recovery in CD4+ cell count and this might partly explain the incident TB in HIV
      infected patients receiving cART. These findings reinforce the importance of
      adjunctive TB preventive therapy for patients with reduced recovery in CD4+ cell
      count.

PMID- 28743249
TI  - Caregiving burden and depression in paid caregivers of hospitalized patients: a
      pilot study in China.
AB  - BACKGROUND: Caregiving burden and depression in family caregivers have been
      investigated, but little is known about how they affect paid caregivers. The aim
      of this study was to investigate caregiving burden and depression in paid
      caregivers of hospitalized patients. METHODS: A cross-sectional survey study was
      conducted in a tertiary referral hospital (Chengdu, China) that enrolled 108 paid
      caregivers who worked in the inpatient department. The Caregiver Burden Inventory
      (CBI) and the Center for Epidemiologic Studies Depression (CES-D) scale were
      incorporated into a self-developed questionnaire to gather demographic
      information on the following four aspects: general, work, income, and family.
      RESULTS: The mean total CBI score was 29.7 +/- 12.5. The time-dependence burden
      had the highest score of 15.3 +/- 4.0, which was followed by the physical burden
      score of 6.5 +/- 4.6, developmental burden score of 3.7 +/- 4.0, social burden
      score of 3.2 +/- 4.0, and emotional burden score of 2.4 +/- 3.1. Multiple linear
      regression analysis showed that a higher CBI was associated with a longer time as
      a paid caregiver [beta=7.041, 95% Confidence Interval (CI):1.935 to 12.974, p =
      0.009], lower income satisfaction (beta= - 6.573, 95% CI: -11.248 to -3.020, p =
      0.001), and higher frequency of meeting with their relatives (beta=7.125, 95% CI:
      2.019 to 12.456, p = 0.006). The mean CES-D score was 11.9 +/- 8.7, and
      significant depression was found in 28 (25.9%) paid caregivers according to the
      CES-D score >= 16 cut-off. There was a moderate positive correlation between the
      CBI and CES-D scores (Pearson's r = 0.452, p < 0.001). CONCLUSIONS: A high
      caregiving burden was commonly observed in paid caregivers of hospitalized
      patients in China, as was a high prevalence of depression symptoms. Several
      associated factors were identified that could be areas for future interventions.

PMID- 28743250
TI  - Child and parent perspectives on healthier side dishes and beverages in
      restaurant kids' meals: results from a national survey in the United States.
AB  - BACKGROUND: Children frequently consume foods from restaurants; considering the
      quick-service sector alone, 1/3 of children eat food from these restaurants on a
      given day, and among these consumers, 1/3 of their daily calories come from fast
      food. Restaurant foods and beverages are second only to grocery store foods and
      beverages in their contribution to total energy intake of U.S. 4- to 11-year
      olds. Shifting their restaurant consumption in healthier directions could have a
      positive impact on child health. In 2014 this study examined self-reported child
      receptivity and parent awareness of child receptivity to ordering a fruit or
      vegetable side dish instead of French fries; and milk, water, or flavored water
      instead of soda/pop with a kids' meal when eating out. Child receptivity to side
      dishes was compared between 2010 and 2014. METHODS: An online survey was
      administered by Nielsen via their Harris Poll Online to a national panel of 711
      parents and their 8- to 12-year-old child, as part of a larger study.
      Frequencies, logistic regressions, t-tests, chi-square tests, and percent
      agreement were used to evaluate child likelihood of ordering certain side dishes;
      receptivity to healthier side dish and beverage alternatives; changes in
      receptivity to healthier sides across years; and parent awareness. RESULTS: A
      majority of children said they were likely to order a meal with a vegetable
      (60%), fruit (78%), or French fry (93%) side dish. They were receptive to
      receiving a fruit or vegetable (FV) side dish instead of French fries (68%); or
      milk, water, or flavored water instead of soda (81%) with their restaurant kids'
      meal. Liking/taste was the most common reason for children's feelings. Child
      receptivity to a FV side dish instead of French fries was high in both years and
      significantly higher in 2014 (t = -2.12, p = 0.034). The majority of parent and
      child reports of child receptivity were concordant (85%). CONCLUSIONS: These
      national survey results indicate that children are receptive to FV side dishes
      and healthier beverage options with their restaurant meals. Their receptivity has
      remained high in the recent past, and parents are aware of child receptivity. An
      opportunity exists for restaurants to leverage child receptivity to healthier
      sides and beverages by providing and promoting healthy options.

PMID- 28743251
TI  - Acceptability of lifelong treatment among HIV-positive pregnant and breastfeeding
      women (Option B+) in selected health facilities in Zimbabwe: a qualitative study.
AB  - BACKGROUND: Zimbabwe's Ministry of Health and Child Care (MOHCC) adopted 2013
      World Health Organization (WHO) prevention of mother-to-child HIV transmission
      (PMTCT) guidelines recommending initiation of HIV-positive pregnant and
      breastfeeding women (PPBW) on lifelong antiretroviral treatment (ART)
      irrespective of clinical stage (Option B+). Option B+ was officially launched in
      Zimbabwe in November 2013; however the acceptability of life-long ART and its
      potential uptake among women was not known. METHODS: A qualitative study was
      conducted at selected sites in Harare (urban) and Zvimba (rural) to explore
      Option B+ acceptability; barriers, and facilitators to ART adherence and service
      uptake. In-depth interviews (IDIs), focus group discussions (FGDs) and key
      informant interviews (KIIs) were conducted with PPBW, healthcare providers, and
      community members. All interviews were audio-recorded, transcribed, and
      translated; data were coded and analyzed in MaxQDA v10. RESULTS: Forty-three
      IDIs, 22 FGDs, and five KIIs were conducted. The majority of women accepted
      lifelong ART. There was however, a fear of commitment to taking lifelong
      medication because they were afraid of defaulting, especially after cessation of
      breastfeeding. There was confusion around dosage; and fear of side effects, not
      having enough food to take drugs, and the lack of opportunities to ask questions
      in counseling. Participants reported the need for strengthening community
      sensitization for Option B+. Facilitators included receiving a simplified pill
      regimen; ability to continue breastfeeding beyond 6 months like HIV-negative
      women; and partner, community and health worker support. Barriers included
      distance of health facility, non-disclosure of HIV status, poor male partner
      support and knowing someone who had negative experience on ART. CONCLUSIONS: This
      study found that Option B+ is generally accepted among PPBW as a means to
      strengthen their health and protect their babies. Consistent with previous
      literature, this study demonstrated the importance of male partner and community
      support in satisfactory adherence to ART and enhancing counseling techniques.
      Strengthening community sensitization and male knowledge is critical to encourage
      women to disclose their HIV status and ensure successful adherence to ART.
      Targeting and engaging partners of women will remain key determinants to women's
      acceptance and adherence on ART under Option B+.

PMID- 28743252
TI  - Quantification of tumour evolution and heterogeneity via Bayesian epiallele
      detection.
AB  - BACKGROUND: Epigenetic heterogeneity within a tumour can play an important role
      in tumour evolution and the emergence of resistance to treatment. It is
      increasingly recognised that the study of DNA methylation (DNAm) patterns along
      the genome - so-called 'epialleles' - offers greater insight into epigenetic
      dynamics than conventional analyses which examine DNAm marks individually.
      RESULTS: We have developed a Bayesian model to infer which epialleles are present
      in multiple regions of the same tumour. We apply our method to reduced
      representation bisulfite sequencing (RRBS) data from multiple regions of one lung
      cancer tumour and a matched normal sample. The model borrows information from all
      tumour regions to leverage greater statistical power. The total number of
      epialleles, the epiallele DNAm patterns, and a noise hyperparameter are all
      automatically inferred from the data. Uncertainty as to which epiallele an
      observed sequencing read originated from is explicitly incorporated by
      marginalising over the appropriate posterior densities. The degree to which
      tumour samples are contaminated with normal tissue can be estimated and corrected
      for. By tracing the distribution of epialleles throughout the tumour we can infer
      the phylogenetic history of the tumour, identify epialleles that differ between
      normal and cancer tissue, and define a measure of global epigenetic disorder.
      CONCLUSIONS: Detection and comparison of epialleles within multiple tumour
      regions enables phylogenetic analyses, identification of differentially expressed
      epialleles, and provides a measure of epigenetic heterogeneity. R code is
      available at github.com/james-e-barrett.

PMID- 28743253
TI  - A qualitative study of carers' experiences of dementia cafes: a place to feel
      supported and be yourself.
AB  - BACKGROUND: Unpaid, informal carers or caregivers play an important role in
      supporting people living with dementia but the role can be challenging and carers
      themselves may benefit from support. Alzheimer's, dementia or memory cafes are
      one such form of support . These cafes are usually provided in the voluntary
      sector and are a place where people with dementia and those supporting them,
      usually family carers, can meet with others in similar situations. METHODS: Using
      semi-structured interviews, this qualitative study explored the experiences of 11
      carers from five dementia cafes in and around London, England. RESULTS: Thematic
      analysis resulted in the identification of four key themes. Cafes provide a
      relaxed, welcoming atmosphere where carers can go where they feel supported and
      accepted. Cafe attendance often brought a sense of normality to these carers'
      lives. Carers and those they care for look forward to going and often enjoy both
      the activities provided and socialising with others. Other highlighted benefits
      included peer support from other carers, information provision and support from
      the volunteer cafe coordinators. Despite diversity in how the cafes were run and
      in the activities offered, there were many reported similarities amongst carers
      in the value ascribed to attending the cafes. CONCLUSIONS: Dementia cafes appear
      to be a valuable, perhaps unique form of support for carers giving them brief
      respite from their caring role. Future research incorporating mixed methods is
      needed to understand the perspectives of those living with dementia.

PMID- 28743254
TI  - Association between serotonin transporter gene polymorphisms and increased
      suicidal risk among HIV positive patients in Uganda.
AB  - BACKGROUND: Persons living with HIV/AIDS (PLWHA) are at an increased risk of
      suicide. Increased suicidal risk is a predictor of future attempted and completed
      suicides and has been associated with poor quality of life and poor adherence
      with antiretroviral therapy. Clinical risk factors have low predictive value for
      suicide, hence the interest in potential neurobiological correlates and specific
      heritable markers of suicide vulnerability. The serotonin transporter gene has
      previously been implicated in the aetiology of increased suicidal risk in non-HIV
      infected study populations and its variations may provide a platform for
      identifying genetic risk for suicidality among PLWHA. The present cross-sectional
      study aimed at identifying two common genetic variants of the serotonin
      transporter gene and their association with increased suicidal risk among human
      immunodeficiency virus (HIV)-positive adults in Uganda. RESULTS: The prevalence
      of increased suicidal risk (defined as moderate to high risk suicidality on the
      suicidality module of the Mini Neuropsychiatric Interview (M.I.N.I) was 3.3% (95%
      CI, 2.0-5.3). The 5-HTTLPR was found to be associated with increased suicidal
      risk before Bonferroni correction (p-value = 0.0174). A protective effect on
      increased suicidal risk was found for the 5-HTTLPR/rs25531 S A allele (p-value =
      0.0046)- which directs reduced expression of the serotonin transporter gene (5
      HTT). CONCLUSION: The S A allele at the 5-HTTLPR/rs25531 locus is associated with
      increased suicidal risk among Ugandan PLWHA. Further studies are needed to
      validate this finding in Ugandan and other sub-Saharan samples.

PMID- 28743255
TI  - Aspirations to become an anaesthetist: longitudinal study of historical trends
      and trajectories of UK-qualified doctors' early career choices and of factors
      that have influenced their choices.
AB  - BACKGROUND: It is important to inform medical educators and workforce planners in
      Anaesthesia about early career choices for the specialty, factors that influence
      them and to elucidate how recent choices of men and women doctors relate to the
      overall historical trends in the specialty's popularity. METHODS: We analysed
      longitudinal data on career choice, based on self-completed questionnaires, from
      national year-of-qualification cohorts of UK-trained doctors from 1974 to 2012
      surveyed one, three and 5 years post-qualification. Career destination data 10
      years post-qualification were used for qualifiers between 1993 and 2002, to
      investigate the association between early choice and later destinations. RESULTS:
      In years 1, 3 and 5 post-qualification, respectively, 59.9% (37,385), 64.6%
      (31,473), and 67.2% (24,971) of contactable doctors responded. There was an
      overall increase, from the early to the later cohorts, in the percentage of
      medical graduates who wished to enter anaesthesia: for instance year 1 choices
      rose from 4.6 to 9.4%, comparing the 1974 and 2012 cohorts. Men were more likely
      than women to express an early preference for a career in anaesthesia: for
      example, at year 3 after qualification anaesthesia was the choice of 10.1% of men
      and 7.9% of women. There was a striking increase in the certainty with which
      women chose anaesthesia as their future career specialty in recent compared to
      earlier cohorts, not reflected in any trends observed in men choosing
      anaesthesia. Sixty percent of doctors who were anaesthetists, 10 years after
      qualifying, had specified anaesthesia as their preferred specialty when surveyed
      in year 1, 80% in year 3, and 92% in year 5. Doctors working as anaesthetists
      were less likely than those working in other hospital specialties to have
      specified, as strong influences on specialty choice, 'experience of the subject'
      as students, 'inclinations before medical school', and 'what I really want to
      do'. Men anaesthetists were more influenced in their specialty choice than men in
      other hospital specialties by 'wanting a career with acceptable hours'; the
      corresponding difference among women was not significant. CONCLUSIONS: We suggest
      a focus on inspirational teaching of anaesthesia in medical school and on greater
      exposure to the specialty in the foundation programme. Factors which may
      discourage women from entering anaesthesia should be explored and addressed.

PMID- 28743256
TI  - A comparison of multiple imputation methods for handling missing values in
      longitudinal data in the presence of a time-varying covariate with a non-linear
      association with time: a simulation study.
AB  - BACKGROUND: Missing data is a common problem in epidemiological studies, and is
      particularly prominent in longitudinal data, which involve multiple waves of data
      collection. Traditional multiple imputation (MI) methods (fully conditional
      specification (FCS) and multivariate normal imputation (MVNI)) treat repeated
      measurements of the same time-dependent variable as just another 'distinct'
      variable for imputation and therefore do not make the most of the longitudinal
      structure of the data. Only a few studies have explored extensions to the
      standard approaches to account for the temporal structure of longitudinal data.
      One suggestion is the two-fold fully conditional specification (two-fold FCS)
      algorithm, which restricts the imputation of a time-dependent variable to time
      blocks where the imputation model includes measurements taken at the specified
      and adjacent times. To date, no study has investigated the performance of two
      fold FCS and standard MI methods for handling missing data in a time-varying
      covariate with a non-linear trajectory over time - a commonly encountered
      scenario in epidemiological studies. METHODS: We simulated 1000 datasets of 5000
      individuals based on the Longitudinal Study of Australian Children (LSAC). Three
      missing data mechanisms: missing completely at random (MCAR), and a weak and a
      strong missing at random (MAR) scenarios were used to impose missingness on body
      mass index (BMI) for age z-scores; a continuous time-varying exposure variable
      with a non-linear trajectory over time. We evaluated the performance of FCS,
      MVNI, and two-fold FCS for handling up to 50% of missing data when assessing the
      association between childhood obesity and sleep problems. RESULTS: The standard
      two-fold FCS produced slightly more biased and less precise estimates than FCS
      and MVNI. We observed slight improvements in bias and precision when using a time
      window width of two for the two-fold FCS algorithm compared to the standard width
      of one. CONCLUSION: We recommend the use of FCS or MVNI in a similar longitudinal
      setting, and when encountering convergence issues due to a large number of time
      points or variables with missing values, the two-fold FCS with exploration of a
      suitable time window.

PMID- 28743257
TI  - Longer travel time to district hospital worsens neonatal outcomes: a
      retrospective cross-sectional study of the effect of delays in receiving
      emergency cesarean section in Rwanda.
AB  - BACKGROUND: In low-resource settings, access to emergency cesarean section is
      associated with various delays leading to poor neonatal outcomes. In this study,
      we described the delays a mother faces when needing emergency cesarean delivery
      and assessed the effect of these delays on neonatal outcomes in Rwanda. METHODS:
      This retrospective study included 441 neonates and their mothers who underwent
      emergency cesarean section in 2015 at three district hospitals in Rwanda. Four
      delays were measured: duration of labor prior to hospital admission, travel time
      from health center to district hospital, time from admission to surgical
      incision, and time from decision for emergency cesarean section to surgical
      incision. Neonatal outcomes were categorized as unfavorable (APGAR <7 at 5 min or
      death) and favorable (alive and APGAR >=7 at 5 min). We assessed the relationship
      between each type of delay and neonatal outcomes using multivariate logistic
      regression. RESULTS: In our study, 9.1% (40 out of 401) of neonates had an
      unfavorable outcome, 38.7% (108 out of 279) of neonates' mothers labored for 12
      24 h before hospital admission, and 44.7% (159 of 356) of mothers were
      transferred from health centers that required 30-60 min of travel time to reach
      the district hospital. Furthermore, 48.1% (178 of 370) of cesarean sections
      started within 5 h after hospital admission and 85.2% (288 of 338) started more
      than 30 min after the decision for cesarean section was made. Neonatal outcomes
      were significantly worse among mothers with more than 90 min of travel time from
      the health center to the district hospital compared to mothers referred from
      health centers located on the same compound as the hospital (aOR = 5.12, p =
      0.02). Neonates with cesarean deliveries starting more than 30 min after decision
      for cesarean section had better outcomes than those starting immediately (aOR =
      0.32, p = 0.04). CONCLUSIONS: Longer travel time between health center and
      district hospital was associated with poor neonatal outcomes, highlighting a need
      to decrease barriers to accessing emergency maternal services. However, longer
      decision to incision interval posed less risk for adverse neonatal outcome. While
      this could indicate thorough pre-operative interventions including triage and
      resuscitation, this relationship should be studied prospectively in the future.

PMID- 28743258
TI  - Trends in smoking behaviour among Estonian physicians in 1982-2014.
AB  - BACKGROUND: Smoking surveys among physicians have proved useful in highlighting
      the importance of physicians as healthy life style exemplars and role models in
      tobacco control and smoking cessation. The aim of this study was to give an
      overview of smoking behaviour among Estonian physicians from 1982 to 2014.
      METHODS: Three cross-sectional postal surveys using a self-administered
      questionnaire were carried out among all practising physicians in Estonia. The
      number of physicians participating in this study was 3786 in 1982, 2735 in 2002,
      and 2902 in 2014. Data analysis involved calculating the age-standardized
      prevalences of smoking, prevalences of smoking by age group and mean age of
      smoking initiation. A non-parametric test for trend was used to assess
      significant changes in smoking over time. RESULTS: Age-standardized prevalence of
      current smoking among men was 39.7% in 1982, 20.9% in 2002, and 14.3% in 2014 and
      among women 12.2%, 8.0%, and 5.2%, respectively (p < 0.0001 for trends). From
      1982 to 2014, the biggest decline of current smoking among men and women was in
      age groups under 35 (from 55.2% to 16.7% and from 16.7% to 2.8%, respectively)
      and 35-44 (from 47.1% to 8.3% and from 19.5% to 5.1%, respectively) (p < 0.0001
      for trends). Mean age of smoking initiation decreased from 20.4 to 19.3 among men
      and from 24.5 to 20.4 among women over the study period. CONCLUSIONS: In 1982
      2014, smoking prevalence among Estonian physicians declined substantially. This
      may influence the willingness of society to recognize the health consequences of
      smoking which could give a support to the decline of the smoking epidemic in the
      country. Differences between smoking among male and female physicians persisted
      over the study period, but mean age of smoking initiation decreased. A further
      decline in smoking among Estonian physicians should be encouraged by special
      efforts targeted at physicians.

PMID- 28743259
TI  - A comparison study between GeXP-based multiplex-PCR and serology assay for
      Mycoplasma pneumoniae detection in children with community acquired pneumonia.
AB  - BACKGROUND: Diagnosis of community-acquired pneumonia (CAP) caused by Mycoplasma
      pneumoniae (Mp) in children has been hampered by difficulty in obtaining
      convalescent serum and time constraints. In this study, the two diagnostic assays
      that targeted respectively on Mp-antibody and Mp-DNA were retrospectively
      investigated. METHODS: A total of 3146 children were clinically diagnosed to have
      CAP and were confirmed by chest X-ray during March 2015 to February 2016 in
      Children's hospital of Hebei Province (China). Both of the sera and sputum
      samples were collected in 24 h after their admission. The Mp-antibody was
      examined by the passive particle agglutination assay and a fourfold or greater
      increase of antibody titers of paired sera or?1:160 titer of single serum was set
      as the serology positive. Mp-DNA in the sputum samples was tested by a multiplex
      PCR method named GeXP assay (multiplex PCR combined with automated capillary
      electrophoresis). In order to eliminate the false positive results caused by the
      asymptomatic carriage after infected by M. pneumoniae, the inconsistent samples
      were tested by the real-time isothermal transcription-mediated RNA amplification
      assay (SAT). RESULTS: The inter-rated agreement test was performed in 3146 CAP
      patients, with a highest kappa value in the school-age children as 0.783. There
      were 6.29% (198/3146) cases showed inconsistent results determined by GeXP and
      serology assay. All of the 19 GeXP(+)/Serology (-) samples and a randomly chosen
      27 from 179 GeXP(-)/Serology (+) samples were tested by SAT assay, and a 97.8%
      diagnosis agreement was observed between SAT and GeXP assay, but not with the
      serology assay. In addition, patients who were detected only by serology or only
      by multiplex-PCR were significantly younger than those with both methods positive
      (3.0 and 1.5 years vs. 5.0 years, p < 0.01). The Viral-Mp coinfection accounted
      for 37.0% (97/262), which was more common in winter and spring (p < 0.05) and in
      the infantile group (p < 0.01), compared to the pure Mp positive ones.
      CONCLUSION: In some children CAP cases, the Mp laboratory diagnosis was
      inconsistent between serology and multiplex-PCR assay. Verified by the SAT assay,
      the GeXP showed a more sensitive and reliable performance compared with the
      serology assay. Furthermore, employing the multiplex-PCR could provide more
      information on the associated pathogens for clinical assessment of CAP.

PMID- 28743260
TI  - Molecular evolution of two asymptomatic echovirus 6 strains that constitute a
      novel branch of recently epidemic echovirus 6 in China.
AB  - BACKGROUND: Echovirus 6 (E6) infections are associated with aseptic meningitis
      and acute flaccid paralysis (AFP). But some infections, sometimes most of them,
      are asymptomatic. The mechanism of E6 virulence is unknown. Analyses of the
      molecular evolution of asymptomatic E6 may help understand why the infections
      show different manifestations. METHODS: Ninety-six stool samples of healthy
      children in Yunnan, China were collected and two E6 strains were isolated from
      them. The whole genomes of these two E6 strains were sequenced, and their
      molecular evolution was analyzed. RESULTS: The results showed that the two E6
      strains may be derived from KJ7724XX strains, which were predominant in AFP
      patients in Shangdong in 2011. The evolution was accelerated when the two E6
      strains formed, although no positive selection site was found. The 11 exclusive
      mutations on which selection force significantly changed were found in the 2C,
      3AB and 3C genes. CONCLUSION: There are some E6 strains which did not cause the
      disease in the children of Yunnan. These E6 strains maybe come from a recombinant
      E6 strain which was associated with the outbreak of AFP in Shangdong in 2011.
      However, some new mutations were found in the 2C, 3AB and 3C genes of these
      asymptomatic strains, and these mutations may be constraint by the natural
      selection and could be potentially responsible for clinical presentations.

PMID- 28743261
TI  - Frequency and predictors of anxiety and depression among pregnant women attending
      tertiary healthcare institutes of Quetta City, Pakistan.
AB  - BACKGROUND: Anxiety and depression (A&D) are commonly reported among pregnant
      women from all over the world; however, there is a paucity of workable data from
      the developing countries including Pakistan. The current study, therefore, aims
      to find out the frequency and predictors of A&D among pregnant women attending a
      tertiary healthcare institutes in the city of Quetta, in the Balochistan
      province, Pakistan. METHODS: A questionnaire based, cross-sectional survey was
      conducted. The pre-validated Hospital Anxiety and Depression Scale (HADS) were
      used to assess the frequency of A&D among study respondents. Anxiety and
      depression scores were calculated via standard scoring procedures while logistic
      regression was used to identify the predictors of A&D. SPSS v. 20 was used for
      data analysis and p < 0.05 was taken as significant. RESULTS: Seven hundred and
      fifty pregnant women responded to the survey. The majority of the respondents
      belonged to age group of 26-35 year (424, 56.4%) and had no formal education
      (283, 37.6%). Furthermore, 612 (81.4%) of the respondents were unemployed and had
      urban residencies (651, 86.6%). The mean anxiety score was 10.08 +/- 2.52; the
      mean depression score was 9.51 +/- 2.55 and the total HADS score was 19.23 +/-
      3.91 indicating moderate A&D among the current cohort. Logistic regression
      analysis reported significant goodness of fit (Chi square = 17.63, p = 0.030, DF
      = 3), indicating that the model was advisable. Among all variables, age had a
      significant association when compared with HADS scores [adjusted OR (odds ratios)
      = 1.23, 95% CI = 1.13-1.62, p < 0.001]. CONCLUSION: Moderate A&D was reported
      among the study respondents. Furthermore, age was highlighted as a predictor of
      A&D. The evidence from this study provides a motion of support programs for
      anxious and depressed pregnant women. The benefits of implementing good mental
      health in antenatal care have long-lasting benefits for both mother and infant.
      Therefore, there is a need to incorporate A&D screening in the existing antenatal
      programs.

PMID- 28743262
TI  - The effects of semantic congruency: a research of audiovisual P300-speller.
AB  - BACKGROUND: Over the past few decades, there have been many studies of aspects of
      brain-computer interface (BCI). Of particular interests are event-related
      potential (ERP)-based BCI spellers that aim at helping mental typewriting.
      Nowadays, audiovisual unimodal stimuli based BCI systems have attracted much
      attention from researchers, and most of the existing studies of audiovisual BCIs
      were based on semantic incongruent stimuli paradigm. However, no related studies
      had reported that whether there is difference of system performance or
      participant comfort between BCI based on semantic congruent paradigm and that
      based on semantic incongruent paradigm. METHODS: The goal of this study was to
      investigate the effects of semantic congruency in system performance and
      participant comfort in audiovisual BCI. Two audiovisual paradigms (semantic
      congruent and incongruent) were adopted, and 11 healthy subjects participated in
      the experiment. High-density electrical mapping of ERPs and behavioral data were
      measured for the two stimuli paradigms. RESULTS: The behavioral data indicated no
      significant difference between congruent and incongruent paradigms for offline
      classification accuracy. Nevertheless, eight of the 11 participants reported
      their priority to semantic congruent experiment, two reported no difference
      between the two conditions, and only one preferred the semantic incongruent
      paradigm. Besides, the result indicted that higher amplitude of ERP was found in
      incongruent stimuli based paradigm. CONCLUSIONS: In a word, semantic congruent
      paradigm had a better participant comfort, and maintained the same recognition
      rate as incongruent paradigm. Furthermore, our study suggested that the paradigm
      design of spellers must take both system performance and user experience into
      consideration rather than merely pursuing a larger ERP response.

PMID- 28743263
TI  - Exposure to ambient particulate matter alters the microbial composition and
      induces immune changes in rat lung.
AB  - BACKGROUND: Ambient particulate matter exposure has been shown to increase the
      risks of respiratory diseases. However, the role of the lung microbiome and the
      immune response to inhaled particulate matter are largely unexplored. We studied
      the influence of biomass fuel and motor vehicle exhaust particles on the lung
      microbiome and pulmonary immunologic homeostasis in rats. METHODS: Fifty-seven
      Sprague-Dawley rats were randomly divided into clean air (CON), biomass fuel
      (BMF), and motor vehicle exhaust (MVE) groups. After a 4-week exposure, the
      microbial composition of the lung was assessed by 16S rRNA pyrosequencing, the
      structure of the lung tissue was assessed with histological analysis, the
      phagocytic response of alveolar macrophages to bacteria was determined by flow
      cytometry, and immunoglobulin concentrations were measured with commercial ELISA
      kits. RESULTS: There was no significant difference in lung morphology between the
      groups. However, the BMF and MVE groups displayed greater bacterial abundance and
      diversity. Proteobacteria were present in higher proportions in the MVE group,
      and 12 bacterial families differed in their relative abundances between the three
      groups. In addition, particulate matter exposure significantly increased the
      capacity of alveolar macrophages to phagocytose bacteria and induced changes in
      immunoglobulin levels. CONCLUSION: We demonstrated that particulate matter
      exposure can alter the microbial composition and change the pulmonary immunologic
      homeostasis in the rat lung.

PMID- 28743264
TI  - Recent developments in immunotherapy of acute myeloid leukemia.
AB  - The advent of new immunotherapeutic agents in clinical practice has
      revolutionized cancer treatment in the past decade, both in oncology and
      hematology. The transfer of the immunotherapeutic concepts to the treatment of
      acute myeloid leukemia (AML) is hampered by various characteristics of the
      disease, including non-leukemia-restricted target antigen expression profile, low
      endogenous immune responses, and intrinsic resistance mechanisms of the leukemic
      blasts against immune responses. However, considerable progress has been made in
      this field in the past few years.Within this manuscript, we review the recent
      developments and the current status of the five currently most prominent
      immunotherapeutic concepts: (1) antibody-drug conjugates, (2) T cell-recruiting
      antibody constructs, (3) chimeric antigen receptor (CAR) T cells, (4) checkpoint
      inhibitors, and (5) dendritic cell vaccination. We focus on the clinical data
      that has been published so far, both for newly diagnosed and refractory/relapsed
      AML, but omitting immunotherapeutic concepts in conjunction with hematopoietic
      stem cell transplantation. Besides, we have included important clinical trials
      that are currently running or have recently been completed but are still lacking
      full publication of their results.While each of the concepts has its particular
      merits and inherent problems, the field of immunotherapy of AML seems to have
      taken some significant steps forward. Results of currently running trials will
      reveal the direction of further development including approaches combining two or
      more of these concepts.

PMID- 28743265
TI  - The predictive value of respiratory function tests for non-invasive ventilation
      in amyotrophic lateral sclerosis.
AB  - BACKGROUND: Non-invasive ventilation (NIV) improves survival and quality of life
      in amyotrophic lateral sclerosis (ALS) patients. The timing of referral to a home
      ventilation service (HVS), which is in part based on respiratory function tests,
      has shown room for improvement. It is currently unknown which respiratory
      function test predicts an appropriate timing of the initiation of NIV. METHODS:
      We analysed, retrospectively, serial data of five respiratory function tests:
      forced vital capacity (FVC), peak cough flow (PCF), maximum inspiratory and
      expiratory pressure (MIP and MEP) and sniff nasal inspiratory pressure (SNIP) in
      patients with ALS. Patients who had had at least one assessment of respiratory
      function and one visit at the HVS, were included. Our aim was to detect the test
      with the highest predictive value for the need for elective NIV in the following
      3 months. We analysed time curves, currently used cut-off values for referral,
      and respiratory function test results between 'NIV indication' and 'no-NIV
      indication' patients. RESULTS: One hundred ten patients with ALS were included of
      whom 87 received an NIV indication; 11.5% had one assessment before receiving an
      NIV indication, 88.5% had two or more assessments. The NIV indication was based
      on complaints of hypoventilation and/or proven (nocturnal) hypercapnia. The five
      respiratory function tests showed a descending trend during disease progression,
      where SNIP showed the greatest decline within the latest 3 months before NIV
      indication (mean = -22%). PCF at the time of referral to the HVS significantly
      discriminated between the groups 'NIV-indication' and 'no NIV-indication yet'
      patients at the first HVS visit: 259 (+/-92) vs. 348 (+/-137) L/min, p = 0.019.
      PCF and SNIP showed the best predictive characteristics in terms of sensitivity.
      CONCLUSION: SNIP showed the greatest decline prior to NIV indication and PCF
      significantly differentiated 'NIV-indication' from 'no NIV-indication yet'
      patients with ALS. Currently used cut-off values might be adjusted and other
      respiratory function tests such as SNIP and PCF may become part of routine care
      in patients with ALS in order to avoid non-timely initiation of (non-invasive)
      ventilation.

PMID- 28743266
TI  - Non-falciparum malaria imported mainly from Africa: a review from a Portuguese
      hospital.
AB  - BACKGROUND: Non-falciparum malaria (NFM) has been reported to be responsible for
      around 25% of imported malaria cases in Europe but is often neglected due to its
      less severe clinical course when compared to Plasmodium falciparum.
      Differentiation between species is however crucial for a correct approach. The
      objective of this study is to report the cases of this often missed aetiology of
      malaria in a tertiary hospital in Portugal. METHODS: Data were retrospectively
      analysed from patients admitted from January 2006 to August 2016 with a NFM
      diagnosis based on microscopy, rapid diagnostic tests (RDT) (BinaxNow(r)) and/or
      PCR. Epidemiologic and clinical aspects were reviewed. RESULTS: A total of 19 NFM
      cases were diagnosed, corresponding to 8.4% of the total 225 cases of malaria.
      Seventeen (89%) were male with a median age of 41 years. All but one case were
      imported from sub-Saharan Africa, with 12 (63%) of the cases returned from
      Angola. Microscopy was positive for all patients and correctly identified the
      species in 12 (63%) patients. BinaxNOW(r) was performed in all patients and it
      was positive in 11 cases, showing a sensitivity of 58%. PCR was performed in nine
      patients and was positive in eight of them, being responsible for the
      identification of the species in four cases. Plasmodium malariae accounted for
      37% (n = 7) of the cases, Plasmodium ovale for 32% (n = 6) and Plasmodium vivax
      for 17% (n = 3). In three (16%) patients, morphology was suggestive of P. vivax
      or P. ovale, but precise species identification was not possible. Regarding
      presentation, fever was the most reported symptom, and the most frequent
      laboratory finding was thrombocytopaenia. Quinine-doxycycline was prescribed in
      eleven patients (58%), chloroquine in six cases (32%) and artemether-lumefantrine
      in two (11%). All of the patients showed clinical improvement. CONCLUSIONS: NFM
      remains an important cause of imported malaria in patients from sub-Saharan
      Africa, alone or as mixed infection with P. falciparum. Access to PCR techniques
      facilitates diagnosis, as low sensitivity from RDTs and microscopy are to be
      expected.

PMID- 28743267
TI  - Production of a recombinant phospholipase A2 in Escherichia coli using resonant
      acoustic mixing that improves oxygen transfer in shake flasks.
AB  - BACKGROUND: Shake flasks are widely used during the development of bioprocesses
      for recombinant proteins. Cultures of recombinant Escherichia coli with orbital
      mixing (OM) have an oxygen limitation negatively affecting biomass growth and
      recombinant-protein production. With the aim to improve mixing and aeration in
      shake flask cultures, we analyzed cultures subjected to OM and the novel resonant
      acoustic mixing (RAM) by applying acoustic energy to E. coli BL21-Gold (DE3): a
      producer of recombinant phospholipase A2 (rPLA2) from Micrurus laticollaris snake
      venom. RESULTS: Comparing OM with RAM (200 rpm vs. 7.5g) at the same initial
      volumetric oxygen transfer coefficient (kLa ~ 80 h-1) ~69% less biomass was
      obtained with OM compared with RAM. We analyzed two more conditions increasing
      agitation until maximal speed (12.5 and 20g), and ~1.6- and ~1.4-fold greater
      biomass was obtained as compared with cultures at 7.5g. Moreover, the specific
      growth rate was statistically similar in all cultures carried out in RAM, but
      ~1.5-fold higher than that in cultures carried out under OM. Almost half of the
      glucose was consumed in OM, whereas between 80 and 100% of the glucose was
      consumed in RAM cultures, doubling biomass per glucose yields. Differential
      organic acid production was observed, but acetate production was prevented at the
      maximal RAM (20g). The amount of rPLA2 in both, OM and RAM cultures, represented
      38 +/- 5% of the insoluble protein. A smaller proportion of alpha-helices and
      beta-sheet of purified inclusion bodies (IBs) were appreciated by ATR-FTIR from
      cultures carried out under OM, than those from RAM. At maximal agitation by RAM,
      internal E. coli localization patterns of protein aggregation changed, as well
      as, IBs proteolytic degradation, in conjunction with the formation of small
      external vesicles, although these changes did not significantly affect the cell
      survival response. CONCLUSIONS: In moderate-cell-density recombinant E. coli BL21
      Gold (DE3) cultures, the agitation increases in RAM (up to the maximum) was not
      enough to avoid the classical oxygen limitation that happens in OM shake flasks.
      However, RAM presents a decrease of oxygen limitation, resulting in a favorable
      effect on biomass growth and volumetric rPLA2 production. While under OM a higher
      recombinant protein yield was obtained.

PMID- 28743268
TI  - The lysosomal protein cathepsin L is a progranulin protease.
AB  - Haploinsufficiency of GRN, the gene encoding progranulin (PGRN), causes
      frontotemporal lobar degeneration (FTLD), the second most common cause of early
      onset dementia. Receptor-mediated lysosomal targeting has been shown to regulate
      brain PGRN levels, and complete deficiency of PGRN is a direct cause of neuronal
      ceroid lipofuscinosis (NCL), a lysosomal storage disease. Here we show that the
      lysosomal cysteine protease cathepsin L (Cat L) can mediate the proteolytic
      cleavage of intracellular PGRN into poly-granulin and granulin fragments.
      Further, PGRN and Cat L co-localize in lysosomes of HEK293 cells, iPSC-derived
      neurons and human cortical neurons from human postmortem tissue. These data
      identify Cat L as a key intracellular lysosomal PGRN protease, and provides an
      intriguing new link between lysosomal dysfunction and FTLD.

PMID- 28743269
TI  - Mesenchymal stem cells from sternum: the type of heart disease, ischemic or
      valvular, does not influence the cell culture establishment and growth kinetics.
AB  - BACKGROUND: In an attempt to increase the therapeutic potential for myocardial
      regeneration, there is a quest for new cell sources and types for cell therapy
      protocols. The pathophysiology of heart diseases may affect cellular
      characteristics and therapeutic results. METHODS: To study the proliferative and
      differentiation potential of mesenchymal stem cells (MSC), isolated from bone
      marrow (BM) of sternum, we made a comparative analysis between samples of
      patients with ischemic (IHD) or non-ischemic valvular (VHD) heart diseases. We
      included patients with IHD (n = 42) or VHD (n = 20), with average age of 60 years
      and no differences in cardiovascular risk factors. BM samples were collected
      (16.4 +/- 6 mL) and submitted to centrifugation with Ficoll-Paque, yielding 4.5
      +/- 1.5 * 107 cells/mL. RESULTS: Morphology, immunophenotype and differentiation
      ability had proven that the cultivated sternal BM cells had MSC features. The
      colony forming unit-fibroblast (CFU-F) frequency was similar between groups (p =
      0.510), but VHD samples showed positive correlation to plated cells vs. CFU-F
      number (r = 0.499, p = 0.049). The MSC culture was established in 29% of
      collected samples, achieved passage 9, without significant difference in
      expansion kinetics between groups (p > 0.05). Dyslipidemia and the use of statins
      was associated with culture establishment for IHD patients (p = 0.049 and p =
      0.006, respectively). CONCLUSIONS: Together, these results show that the sternum
      bone can be used as a source for MSC isolation, and that ischemic or valvular
      diseases do not influence the cellular yield, culture establishment or in vitro
      growth kinetics.

PMID- 28743270
TI  - Pre-transplant depression as a predictor of adherence and morbidities after
      orthotopic heart transplantation.
AB  - BACKGROUND: Psychosocial factors are useful predictors of adverse outcomes after
      solid organ transplantation. Although depression is a known predictor of poor
      outcomes in patients who undergo orthotopic heart transplantation (OHT) and is
      actively screened for during pre-transplant evaluation, the effects of early
      identification of this entity on post-transplant outcomes are not clearly
      understood. The purpose of this study was to evaluate the impact of pre
      transplant depression on outcomes after OHT. METHOD: In this retrospective study,
      51 patients that underwent psychosocial evaluation performed by a social worker
      prior to the transplant and followed up in our center post-transplant were
      enrolled. Patients were stratified by the presence/absence of depression during
      the initial encounter. Primary end-points were overall survival, 1st-year
      hospitalizations, overall hospitalizations, rejections, and compliance with
      medications and outpatient appointments. RESULTS: Depressed patients were 3.5
      times more likely to be non-compliant with medications; RR = 3.5, 95% CI
      (1.2,10.2), p = 0.046 and had higher incidence of first year hospitalizations
      (4.7 +/- 3.1 vs. 2.2 +/- 1.9, p = 0.046), shorter time to first hospitalization
      25 days (IQR 17-39) vs. 100 days (IQR 37-229), p = 0.001. Patients with
      depression also had higher overall hospitalizations (8.3 +/- 4.4 vs. 4.6 +/- 4.2,
      p = 0.025,) and higher number of admissions for infections (2.8 +/- 1.3 vs. 1.5
      +/- 1.4, p = 0.018) compared to patients without depression. There were no
      statistically significant differences in total number of rejections or compliance
      with outpatient appointments. Kaplan-Meier survival analysis did not reveal
      differences between the two groups (mean 3705 vs. 3764 days, log-rank p = 0.52).
      CONCLUSION: Depression was a strong predictor of poor medication compliance and
      higher rates of hospitalization in transplant recipients. No difference in
      survival between depressed and non-depressed patients after OHT was noted.

PMID- 28743271
TI  - Development of inducer-free expression plasmids based on IPTG-inducible promoters
      for Bacillus subtilis.
AB  - BACKGROUND: Besides Escherichia coli, Bacillus subtilis is an important bacterial
      species for the production of recombinant proteins. Recombinant genes are
      inserted into shuttle expression vectors which replicate in both E. coli and in
      B. subtilis. The ligation products are first transformed into E. coli cells,
      analyzed for correct insertions, and the correct recombinant plasmids are then
      transformed into B. subtilis. A major problem using E. coli cells can be the
      strong basal level of expression of the recombinant protein which may interfere
      with the stability of the cells. To minimize this problem, we developed strong
      expression vectors being repressed in E. coli and inducer-free in B. subtilis.
      RESULTS: In general, induction of IPTG-inducible expression vectors is determined
      by the regulatory lacI gene encoding the LacI repressor in combination with the
      lacO operator on the promoter. To investigate the inducer-free properties of the
      vectors, we constructed inducer-free expression plasmids by removing the lacI
      gene and characterized their properties. First, we examined the ability to
      repress a reporter gene in E. coli, which is a prominent property facilitating
      the construction of the expression vectors carrying a target gene. The beta
      galactosidase (bgaB gene) basal levels expressed from Pgrac01-bgaB could be
      repressed at least twice in the E. coli cloning strain. Second, the inducer-free
      production of BgaB from four different plasmids with the Pgrac01 promoter in B.
      subtilis was investigated. As expected, BgaB expression levels of inducer-free
      constructs are at least 37 times higher than that of the inducible constructs in
      the absence of IPTG, and comparable to those in the presence of the inducer.
      Third, using efficient IPTG-inducible expression vectors containing the strong
      promoter Pgrac100, we could convert them into inducer-free expression plasmids.
      The BgaB production levels from the inducer-free plasmid in the absence of the
      inducer were at least 4.5 times higher than that of the inducible vector using
      the same promoter. Finally, we used gfp as a reporter gene in combination with
      the two promoters Pgrac01 and Pgrac100 to test the new vector types. The GFP
      expression levels could be repressed at least 1.5 times for the Pgrac01-gfp+
      inducer-free construct in E. coli. The inducer-free constructs Pgrac01-gfp+ and
      Pgrac100-gfp+ allowed GFP expression at high levels from 23 * 104 to 32 * 104 RFU
      units and 9-13% of total intracellular proteins. We could reconfirm the two major
      advantages of the new inducer-free expression plasmids: (1) Strong repression of
      the target gene expression in the E. coli cloning strain, and (2) production of
      the target protein at high levels in B. subtilis in the absence of the inducer.
      CONCLUSIONS: We propose a general strategy to generate inducer-free expression
      vector by using IPTG-inducible vectors, and more specifically we developed
      inducer-free expression plasmids using IPTG-inducible promoters in the absence of
      the LacI repressor. These plasmids could be an excellent choice for high-level
      production of recombinant proteins in B. subtilis without the addition of inducer
      and at the same time maintaining a low basal level of the recombinant proteins in
      E. coli. The repression of the recombinant gene expression would facilitate
      cloning of genes that potentially inhibit the growth of E. coli cloning strains.
      The inducer-free expression plasmids will be extended versions of the current
      available IPTG-inducible expression vectors for B. subtilis, in which all these
      vectors use the same cognate promoters. These inducer-free and previously
      developed IPTG-inducible expression plasmids will be a useful cassette to study
      gene expression at a small scale up to a larger scale up for the production of
      recombinant proteins.

PMID- 28743272
TI  - Establishment of Neurospora crassa as a host for heterologous protein production
      using a human antibody fragment as a model product.
AB  - BACKGROUND: Filamentous fungi are commonly used as production hosts for bulk
      enzymes in biotechnological applications. Their robust and quick growth combined
      with their ability to secrete large amounts of protein directly into the culture
      medium makes fungi appealing organisms for the generation of novel production
      systems. The red bread mold Neurospora crassa has long been established as a
      model system in basic research. It can be very easily genetically manipulated and
      a wealth of molecular tools and mutants are available. In addition, N. crassa is
      very fast growing and non-toxic. All of these features point to a high but so far
      untapped potential of this fungus for biotechnological applications. In this
      study, we used genetic engineering and bioprocess development in a design-build
      test-cycle process to establish N. crassa as a production host for heterologous
      proteins. RESULTS: The human antibody fragment HT186-D11 was fused to a truncated
      version of the endogenous enzyme glucoamylase (GLA-1), which served as a carrier
      protein to achieve secretion into the culture medium. A modular expression
      cassette was constructed and tested under the control of different promoters.
      Protease activity was identified as a major limitation of the production strain,
      and the effects of different mutations causing protease deficiencies were
      compared. Furthermore, a parallel bioreactor system (1 L) was employed to develop
      and optimize a production process, including the comparison of different culture
      media and cultivation parameters. After successful optimization of the production
      strain and the cultivation conditions an exemplary scale up to a 10 L stirred
      tank reactor was performed. CONCLUSIONS: The data of this study indicate that N.
      crassa is suited for the production and secretion of heterologous proteins.
      Controlling expression by the optimized promoter Pccg1nr in a fourfold protease
      deletion strain resulted in the successful secretion of the heterologous product
      with estimated yields of 3 mg/L of the fusion protein. The fungus could easily be
      cultivated in bioreactors and a first scale-up was successful. The system holds
      therefore much potential, warranting further efforts in optimization.

PMID- 28743273
TI  - Erratum to: Psychometric evaluation of the canine brief pain inventory in a
      Swedish sample of dogs with pain related to osteoarthritis.

PMID- 28743274
TI  - Risk factors and a prediction model for lower limb lymphedema following
      lymphadenectomy in gynecologic cancer: a hospital-based retrospective cohort
      study.
AB  - BACKGROUND: Lower limb lymphedema (LLL) is a chronic and incapacitating condition
      afflicting patients who undergo lymphadenectomy for gynecologic cancer. This
      study aimed to identify risk factors for LLL and to develop a prediction model
      for its occurrence. METHODS: Pelvic lymphadenectomy (PLA) with or without para
      aortic lymphadenectomy (PALA) was performed on 366 patients with gynecologic
      malignancies at Yaizu City Hospital between April 2002 and July 2014; we
      retrospectively analyzed 264 eligible patients. The intervals between surgery and
      diagnosis of LLL were calculated; the prevalence and risk factors were evaluated
      using the Kaplan-Meier and Cox proportional hazards methods. We developed a
      prediction model with which patients were scored and classified as low-risk or
      high-risk. RESULTS: The cumulative incidence of LLL was 23.1% at 1 year, 32.8% at
      3 years, and 47.7% at 10 years post-surgery. LLL developed after a median 13.5
      months. Using regression analysis, body mass index (BMI) >=25 kg/m2 (hazard ratio
      [HR], 1.616; 95% confidence interval [CI], 1.030-2.535), PLA + PALA (HR, 2.323;
      95% CI, 1.126-4.794), postoperative radiation therapy (HR, 2.469; 95% CI, 1.148
      5.310), and lymphocyst formation (HR, 1.718; 95% CI, 1.120-2.635) were found to
      be independently associated with LLL; age, type of cancer, number of lymph nodes,
      retroperitoneal suture, chemotherapy, lymph node metastasis, herbal medicine,
      self-management education, or infection were not associated with LLL. The
      predictive score was based on the 4 associated variables; patients were
      classified as high-risk (scores 3-6) and low-risk (scores 0-2). LLL incidence was
      significantly greater in the high-risk group than in the low-risk group (HR,
      2.19; 95% CI, 1.440-3.324). The cumulative incidence at 5 years was 52.1% [95%
      CI, 42.9-62.1%] for the high-risk group and 28.9% [95% CI, 21.1-38.7%] for the
      low-risk group. The area under the receiver operator characteristics curve for
      the prediction model was 0.631 at 1 year, 0.632 at 3 years, 0.640 at 5 years, and
      0.637 at 10 years. CONCLUSION: BMI >=25 kg/m2, PLA + PALA, lymphocyst formation,
      and postoperative radiation therapy are significant predictive factors for LLL.
      Our prediction model may be useful for identifying patients at risk of LLL
      following lymphadenectomy. Providing an intensive therapeutic strategy for high
      risk patients may help reduce the incidence of LLL and conserve the quality of
      life.

PMID- 28743275
TI  - Block copolymer conjugated Au-coated Fe3O4 nanoparticles as vectors for enhancing
      colloidal stability and cellular uptake.
AB  - BACKGROUND: Polymer surface-modified inorganic nanoparticles (NPs) provide a
      multifunctional platform for assisting gene delivery. Rational structure design
      for enhancing colloidal stability and cellular uptake is an important strategy in
      the development of safe and highly efficient gene vectors. RESULTS: Heterogeneous
      Au-coated Fe3O4 (Fe3O4@Au) NPs capped by polyethylene glycol-b-poly1-(3
      aminopropyl)-3-(2-methacryloyloxy propylimidazolium bromine) (PEG-b-PAMPImB
      Fe3O4@Au) were prepared for DNA loading and magnetofection assays. The Au outer
      shell of the NPs is an effective platform for maintaining the superparamagnetism
      of Fe3O4 and for PEG-b-PAMPImB binding via Au-S covalent bonds. By forming an
      electrostatic complex with DNA at the inner PAMPImB shell, the magnetic
      nanoplexes offer steric protection from the outer corona PEG, thereby promoting
      high colloidal stability. Transfection efficiency assays in human esophageal
      cancer cells (EC109) show that the nanoplexes have high transfection efficiency
      at a short incubation time in the presence of an external magnetic field, due to
      increased cellular internalization via magnetic acceleration. Finally, after
      transfection with the magnetic nanoplexes EC109 cells acquire magnetic
      properties, thus allowing for selective separation of transfected cells.
      CONCLUSION: Precisely engineered architectures based on neutral-cationic block
      copolymer-conjugated heterogeneous NPs provide a valuable strategy for improving
      the applicability and efficacy of synthesized vectors.

PMID- 28743276
TI  - Suppressing miR-199a-3p by promoter methylation contributes to tumor
      aggressiveness and cisplatin resistance of ovarian cancer through promoting DDR1
      expression.
AB  - BACKGROUND: Discoidin Domain Receptor 1 (DDR1) belongs to the family of collagen
      receptor tyrosine kinases that confers the progression of various cancers.
      Aberrant expression of DDR1 was detected in several human cancers including
      ovarian cancer, which had been shown to increase the migration and invasion of
      tumor cells. However, the precise mechanisms underlying the abnormal expression
      of DDR1 in ovarian cancer has not been well investigated in previous studies.
      RESULTS: In this work, a negative correlation between DDR1 and a tumor suppressor
      miRNA, miR-199a-3p, was observed in ovarian cancer tissues. Furthermore, in vitro
      experimental results confirmed that miR-199a-3p decreased the expression of DDR1
      via targeting the 3'UTR of DDR1 mRNA. To explore the mechanisms for miR-199a-3p
      silence in ovarian cancer, the methylation status of the miR-199a promoter was
      analyzed in ovarian epithelial or cancer cells by methylation-specific PCR and
      bisulphite sequencing. As expected, the miR-199a promoter was hypermethylated in
      ovarian cancer cells but not in normal ovarianepithelial cells. Interestingly,
      knockdown of DNA methyltransferase 3A (DNMT3A) notably increased miR-199a-3p
      level and then attenuated the expression of DDR1 in ovarian cancer cells, which
      suggested that DNMT3A was responsible for the miR-199a promoter hypermethylation.
      Phenotype experiments showed that overexpression of miR-199a-3p significantly
      impaired the migratory, invasive, and tumorigenic capabilities of ovarian cancer
      cells as well as enhanced cisplatin resistance through inhibiting DDR1
      expression. CONCLUSION: These findings demonstrate a critical role of miR-199a
      3p/DDR1 pathway in ovarian cancer development.

PMID- 28743277
TI  - Stroke survivors' long-term QALY-weights in relation to their spouses' QALY
      weights and informal support: a cross-sectional study.
AB  - BACKGROUND: Healthcare interventions that have positive effects on the stroke
      survivors' health-related quality of life (HRQoL) and quality-adjusted life-years
      (QALYs) might also have positive effects for their spouses in terms of improved
      HRQoL and/or reduced spousal informal support. However, knowledge about stroke
      survivors' HRQoL and QALY and the consequences for their spouses' HRQoL and QALY
      is limited. Therefore, the aim of this study was to describe the HRQoL and QALY
      weights in dyads of stroke survivors in comparison with dyads of healthy
      controls, and to study the relationship between the stroke survivors' QALY
      weights and consequences for spouses in terms of QALY-weight and annual cost of
      informal support, using a long-term perspective. METHODS: Data on stroke
      survivors, controls, and spouses were collected from the seven-year follow-up of
      the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). HRQoL was assessed by
      the SF-36, and the preference-based health state values were assessed with the SF
      6D. The magnitude of the support was assessed with a study specific time-diary.
      An ordinary least squares (OLS) regression was used to estimate the association
      between stroke survivors' and spouses' QALY-weights. A two-part econometric model
      was used to estimate the association between stroke survivors' QALY-weights and
      the time spent and cost of spouses' informal support. RESULTS: Cohabitant dyads
      of 248 stroke survivors' aged <70 at stroke onset and 245 controls were included
      in the study. Stroke survivors had lower HRQoL in the SF-36 domains physical
      functioning, physical role, general health, vitality (P < 0.001), and social
      functioning (P = 0.005) in comparison with their cohabitant spouses. There was no
      significant difference in HRQoL for the dyads of controls. The results from the
      regression analyses showed that lower QALY-weights of the stroke survivors were
      associated with lower QALY-weights of their spouses and increased annual cost of
      spousal informal support. CONCLUSION: Our results show that the QALY-weights for
      stroke survivors had consequences for their spouses in terms of annual cost of
      spousal informal support and QALY-weights. Hence, economic evaluation of
      interventions that improve the HRQoL of the stroke survivors but ignore the
      consequences for their spouses may underestimate the value of the intervention.

PMID- 28743278
TI  - Status of insecticide resistance in Anopheles mosquitoes in Ubon Ratchathani
      province, Northeastern Thailand.
AB  - BACKGROUND: Malaria is common in hilly, forested areas along national borders in
      Southeast Asia. Insecticide resistance in malaria vectors has been detected in a
      few countries in the Greater Mekong sub-region (GMS), representing a threat to
      malaria control and prevention. This study aims to determine the insecticide
      resistance status of Anopheles mosquitoes in Ubon Ratchathani province,
      northeastern Thailand, where increasing number of malaria cases were reported
      recently. METHODS: Mosquitoes were collected in 2013-2015 using human landing and
      cattle bait collections in six sites during both the rainy and dry seasons.
      Mosquitoes were first morphologically identified to species and their
      susceptibility status to deltamethrin (0.05%), permethrin (0.75%) and DDT (4%)
      investigated, according to WHO guidelines. Bioassays with the synergists PBO and
      DEF were carried out to address the role of detoxifying enzymes in insecticide
      resistance. DNA sequencing of a fragment of the voltage-gated sodium channel gene
      was carried out to detect knock-down resistance (kdr) substitutions at position
      1014 in resistant species. RESULTS: Due to low vector abundance, complete
      bioassays (n >= 100 mosquitoes) were only achieved for Anopheles hyrcanus s.l.,
      which was resistant to all insecticides tested (mortality ranged from 45 to 87%).
      Suspected resistance to DDT was found in Anopheles barbirostris s.l. (mortality
      69%), but it was susceptible to deltamethrin (mortality 97-100%) and permethrin
      (mortality 100%). Although insufficient number of primary vectors were collected,
      results showed that Anopheles dirus s.l. and Anopheles maculatus s.l. were
      susceptible to deltamethrin (mortality 100%). Anopheles nivipes and Anopheles
      philippinensis were susceptible to all three insecticides. PBO significantly
      increased mortality to deltamethrin and permethrin in pyrethroid-resistant An.
      hyrcanus s.l. None of the sequenced specimens presented the L1014F or L1014S
      mutation. DISCUSSION: This study shows that insecticide resistance is present in
      potential malaria vectors in northeastern Thailand. The absence of kdr mutations
      in all Anopheles species tested suggests that metabolic resistance is the main
      mechanism of pyrethroid resistance. This study provides new findings about
      insecticide susceptibility status of potential malaria vectors in northeastern
      Thailand that are deemed important to guide malaria vector control.

PMID- 28743279
TI  - Childhood interstitial lung diseases in immunocompetent children in Australia and
      New Zealand: a decade's experience.
AB  - BACKGROUND: Childhood interstitial lung disease (chILD) represents a rare
      heterogeneous group of respiratory disorders. In the absence of randomized
      controlled clinical trials, global collaborations have utilized case series with
      an aim to standardising approaches to diagnosis and management. Australasian data
      are lacking. The aim of this study was to calculate prevalence and report the
      experience of chILD in Australasia over a decade. METHODS: Paediatric
      pulmonologists in Australia and New Zealand involved in the care of patients aged
      0-18 years with chILD completed a questionnaire on demographics, clinical
      features and outcomes, over a 10 year period. These data, together with data from
      the 2 reference genetics laboratories, were used to calculate prevalence.
      RESULTS: One hundred fifteen cases were identified equating to a period
      prevalence (range) of 1.5 (0.8-2.1) cases/million for children aged 0-18years.
      Clinical data were provided on 106 patients: the <2 year group comprised 66
      children, median age (range) 0.50 years (0.01-1.92); the >=2 year group comprised
      40 children, median age 8.2 years (2.0-18.0). Management approach was
      heterogeneous. Overall, 79% of patients had a good clinical outcome. Mortality
      rate was 7% in the study population. CONCLUSION: chILD is rare in Australasia.
      This study demonstrates variation in the investigations and management of chILD
      cases across Australasia, however the general outcome is favorable. Further
      international collaboration will help finesse the understanding of these
      disorders.

PMID- 28743280
TI  - Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic
      traits via delivery of miRNA-222-3p.
AB  - BACKGROUND: Although gemcitabine-based chemotherapy has been established as a
      core multimodal therapy for non-small cell lung cancer (NSCLC) treatment, its
      clinical efficacy remains limited by the development of acquired resistance
      following tumor metastasis and relapse. In this study, we investigated how
      gemcitabine-resistant (GR) cells contribute to the development of NSCLC tumor
      malignancy via exosome-mediated transfer of microRNAs. METHODS: We first studied
      the mechanism of exosome internalization via PKH-67 staining and an
      immunofluorescence assay, then confirmed our finding by transmission electron
      microscopy and western blot analysis. Candidate miRNAs were identified through
      microarray analysis. Thereafter, RT-PCR, MTS, Transwell and soft agar assays were
      performed to assess the role of exosomic miR-222-3p in vitro. A 3' untranslated
      region reporter assay was applied to identify the target of miR-222-3p. A lung
      metastasis mouse model was constructed to evaluate tumor growth and metastasis in
      vivo. Finally, clinical samples were used for correlation analysis between
      exosomic miR-222-3p levels and patients' response to gemcitabine. RESULTS: A549
      GR-derived exosomes were internalized by receipt cells via caveolin- and lipid
      raft-dependent endocytosis, which allowed the transfer of miR-222-3p. Exosomic
      miR-222-3p enhanced the proliferation, gemcitabine resistance, migration,
      invasion, and anti-anoikis of parental sensitive cells by directly targeting the
      promoter of SOCS3. In addition, a higher level of exosomic miR-222-3p in sera
      usually predicted worse prognosis in NSCLC patients. CONCLUSION: Our data
      demonstrate that exosomic-miR-222-3p functions as a principal regulator of
      gemcitabine resistance and malignant characteristics by targeting SOCS3. The
      exosomic miR-222-3p level in sera may be a potential prognostic biomarker for
      predicting gemcitabine sensitivity in NSCLC patients.

PMID- 28743281
TI  - A lifestyle intervention study targeting individuals with low socioeconomic
      status of different ethnic origins: important aspects for successful
      implementation.
AB  - BACKGROUND: Evaluation of the implementation process of trials is important,
      because the way a study is implemented modifies its outcomes. Furthermore,
      lessons learned during implementation can inform other researchers on factors
      that play a role when implementing interventions described in research. This
      study evaluates the implementation of the MetSLIM study, targeting individuals
      with low socioeconomic status of different ethnic origins. The MetSLIM study was
      set up to evaluate the effectiveness of a lifestyle programme on waist
      circumference and other cardio-metabolic risk factors. The objective of this
      evaluation was to identify components that were essential for the implementation
      of the MetSLIM study and to inform other researchers on methodological aspects
      when working with inadequately reached populations in health research. METHODS:
      In this evaluation study the experiences of health professionals, study
      assistants, a community worker and regional research coordinators involved in the
      MetSLIM study were explored using semi-structured interviews. Questionnaires were
      used to evaluate participants' satisfaction with the lifestyle intervention.
      RESULTS: Our analyses show that a flexible recruitment protocol eventually leads
      to recruitment of sufficient participants; that trust in the recruiter is an
      important factor in the recruitment of individuals with low socioeconomic status
      of different ethnic origins; and that health professionals will unavoidably shape
      the form of intervention activities. Furthermore, our evaluation shows that daily
      practice and research mutually influence each other and that the results of an
      intervention are a product of this interaction. CONCLUSIONS: Health promotion
      research would benefit from a perspective that sees intervention activities not
      as fixed entities but rather as social interaction that can take on numerous
      forms. Analysing and reporting the implementation process of studies, like in
      this evaluation, will allow readers to get a detailed view on the appropriateness
      of the (intended) study design and intervention for the targeted population.
      Evaluation studies that shed light on the reasons for adaptations, rather than
      describing them as deviation from the original plan, would point out
      methodological aspects important for a study's replication. Furthermore, they
      would show how various factors can influence the implementation, and therewith
      initiate a learning cycle for the development of future intervention studies.
      TRIAL REGISTRATION: Netherlands Trial Register NTR3721 (since November 27, 2012).

PMID- 28743282
TI  - A hospital based surveillance of metallo-beta-lactamase producing gram negative
      bacteria in Nepal by imipenem-EDTA disk method.
AB  - BACKGROUND: A rising threat of the rapid spread of acquired metallo-beta
      lactamases (MBLs) among major Gram-negative pathogens is a matter of public
      health concern worldwide. Hence, for a low income nation like Nepal, surveillance
      data on MBL producing clinical isolates via a cost effective technique is
      necessary to prevent their dissemination as well as formulation and regulation of
      antimicrobial stewardship policy. METHODS: The prospective study was conducted at
      Nepal Medical College, Kathmandu from May to October, 2014 to assess the
      prevalence of MBL production among ceftazidime-resistant Gram-negative rods
      (GNRs) isolates. The samples were processed according to standard microbiological
      procedure following the Manual of clinical Microbiology. Isolated GNRs were
      subjected to susceptibility testing against the selected panel of antibiotics by
      Kirby- Bauer disc diffusion method and interpretation made in conformity with the
      Clinical and Laboratory Standards Institute (CLSI) guidelines. Ceftazidime
      resistant isolates were subjected to the detection of MBL production by imipenem
      EDTA combined disc (CD) method. RESULTS: Among the Gram-negative isolates, 5.80%
      (21/362) were found to be MBL positive with Acinetobacter spp. showing the
      highest prevalence i.e. 85.71% (18/21), followed by P. aeruginosa i.e. 14.29%
      (3/21). None of the other cefazidime resistant gram negative bacteria tested were
      found to be positive for MBL production with all the positive isolates determined
      to be Multidrug resistant (MDR) strains. CONCLUSION: This study demonstrated a
      higher rate of resistance among P. aeruginosa and Acinetobacter spp. to a wide
      variety of antibiotic categories with an additional burden of MBL production
      within them, warranting a need for strict surveillance and rapid detection of MBL
      production among the GNRs.

PMID- 28743283
TI  - Spatial population dynamics and temporal analysis of the distribution of
      Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae)
      in the city of Clorinda, Formosa, Argentina.
AB  - BACKGROUND: Lutzomyia longipalpis, the vector for the causal agent of visceral
      leishmaniasis (VL), has extended its distribution in the southern cone in the
      Americas. The first urban record of Lu. longipalpis in Argentina was from the
      City of Clorinda in 2004. The aim of this study was to analyse the monthly
      distribution and abundance of Lu. longipalpis and to evaluate its association
      with environmental and climatic variables in Clorinda City, Province of Formosa.
      METHODS: Phlebotominae sampling was performed using CDC light mini-traps that
      were placed in different sites of the city between January 2012 and December
      2013. Environmental variables including the normalised difference vegetation
      index, normalized difference water index, land surface temperature and
      precipitation were evaluated using a spatiotemporal model. RESULTS: A total of
      4996 phlebotomine sandflies were captured during the study period, and eight
      species were reported: Lu. longipalpis, Migonemyia migonei, Nyssomyia whitmani,
      Ny. neivai, Brumptomyia guimaraesi, Evandromyia cortelezzii/sallesi, Psathyromyia
      bigeniculata and Expapillata firmatoi. This is the first urban record of Ex.
      firmatoi in Argentina. Lutzomyia longipalpis was the most abundant species
      between 2012 and 2013, and it appeared in all the sampled sites. Moreover, the
      model applied showed that ground humidity and temperature were significantly
      associated with the abundance of Lu. longipalpis. CONCLUSIONS: This longitudinal
      approach at city scale allows for modelling that explains more than 60% of the
      temporal variability of the abundance of Lu. longipalpis based exclusively on
      satellite obtained data. The results support the hypothesis of steady 'hot spots'
      of abundance with time, while other sites could change its abundance due to
      eventual microenvironment changes. The Lu. longipalpis abundance driving factors
      are breeding site-related variables, highlighting the importance both for
      modelling and surveillance to use lag data.

PMID- 28743284
TI  - Hypertension prevalence and influence of basal metabolic rate on blood pressure
      among adult students in Bangladesh.
AB  - BACKGROUND: Hypertension is a global health issue and is currently increasing at
      rapid pace in South Asian countries including Bangladesh. Although, some studies
      on hypertension have been conducted in Bangladesh, there is a lack of scientific
      evidence in the adult student population that was missing from the previous and
      recent national cross-sectional studies. Moreover, the specific risk factors of
      hypertension in the Bangladeshi adults still need to be investigated. This study
      was conducted to estimate hypertension prevalence among adult students in
      Bangladesh and to test the hypothesis of Luke et al. (Hypertension 43:555-560,
      2004) that basal metabolic rate (BMR) and blood pressure are positively
      associated independent of body size. METHOD: The data was collected on 184 adult
      university students (118 female and 66 male) in Dhaka, Bangladesh.
      Anthropometric, BMR details and an average of at least two blood pressure
      measurements were obtained. Hypertension was defined by a systolic blood pressure
      (SBP) >= 140 mmHg and/or, diastolic blood pressure (DBP) >= 90 mmHg. RESULTS:
      Overall, 6.5% of participants had hypertension with significantly (p < 0.001)
      higher prevalence in male (12.1%) than in the female (3.4%) students. Age and BMI
      showed positive and significant correlation with hypertension among the students.
      When adjusted for body mass index (BMI), as well as other potentially confounding
      variables such as age, sex, smoking status and degree of urbanization, BMR was
      positively correlated with SBP and DBP (p < 0.001). Thus, higher BMR is
      associated with SBP and DBP; this is opposite the well documented inverse
      relationship between physical activity and blood pressure. If the influence of
      BMR on blood pressure is confirmed, the systematically elevated BMR might be an
      important predictor that can explain relatively high blood pressure and
      hypertension in humans. CONCLUSION: This study reports the prevalence and
      associated risk factors of hypertension in the Bangladeshi adult students. The
      study also showed a positive association between BMR and blood pressure among the
      participants. A large scale longitudinal study across the country is needed to
      find out the underlying causes of hypertension in the Bangladeshi adults. In
      addition, comprehensive and integrated intervention programs focusing on
      modifiable risk factors are recommended to make awareness and prevent
      hypertension.

PMID- 28743285
TI  - beta adrenergic receptor/cAMP/PKA signaling contributes to the intracellular Ca2+
      release by tentacle extract from the jellyfish Cyanea capillata.
AB  - BACKGROUND: Intracellular Ca2+ overload induced by extracellular Ca2+ entry has
      previously been confirmed to be an important mechanism for the cardiotoxicity as
      well as the acute heart dysfunction induced by jellyfish venom, while the
      underlying mechanism remains to be elucidated. METHODS: Under extracellular Ca2+
      free or Ca2+-containing conditions, the Ca2+ fluorescence in isolated adult mouse
      cardiomyocytes pre-incubated with tentacle extract (TE) from the jellyfish Cyanea
      capillata and beta blockers was scanned by laser scanning confocal microscope.
      Then, the cyclic adenosine monophosphate (cAMP) concentration and protein kinase
      A (PKA) activity in primary neonatal rat ventricular cardiomyocytes were
      determined by ELISA assay. Furthermore, the effect of propranolol against the
      cardiotoxicity of TE was evaluated in Langendorff-perfused rat hearts and intact
      rats. RESULTS: The increase of intracellular Ca2+ fluorescence signal by TE was
      significantly attenuated and delayed when the extracellular Ca2+ was removed. The
      beta adrenergic blockers, including propranolol, atenolol and esmolol, partially
      inhibited the increase of intracellular Ca2+ in the presence of 1.8 mM
      extracellular Ca2+ and completely abolished the Ca2+ increase under an
      extracellular Ca2+-free condition. Both cAMP concentration and PKA activity were
      stimulated by TE, and were inhibited by the beta adrenergic blockers.
      Cardiomyocyte toxicity of TE was antagonized by beta adrenergic blockers and the
      PKA inhibitor H89. Finally, the acute heart dysfuction by TE was antagonized by
      propranolol in Langendorff-perfused rat hearts and intact rats. CONCLUSIONS: Our
      findings indicate that beta adrenergic receptor/cAMP/PKA signaling contributes to
      the intracellular Ca2+ overload through intracellular Ca2+ release by TE from the
      jellyfish C. capillata.

PMID- 28743286
TI  - CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary
      Sjogren's syndrome patients and correlates with focus score and disease activity.
AB  - BACKGROUND: Primary Sjogren's syndrome (pSS) is a common chronic autoimmune
      disease characterized by lymphocytic infiltration of exocrine glands and
      peripheral lymphocyte perturbation. In the current study, we aimed to investigate
      the possible pathogenic implication of autophagy in T lymphocytes in patients
      with pSS. METHODS: Thirty consecutive pSS patients were recruited together with
      20 patients affected by sicca syndrome and/or chronic sialoadenitis and 30
      healthy controls. Disease activity and damage were evaluated according to SS
      disease activity index, EULAR SS disease activity index, and SS disease damage
      index. T lymphocytes were analyzed for the expression of autophagy-specific
      markers by biochemical, molecular, and histological assays in peripheral blood
      and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were
      quantified by enzyme-linked immunosorbent assay. RESULTS: Our study provides
      evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte
      salivary glands from pSS patients. Furthermore, a statistically significant
      correlation was detected between lymphocyte autophagy levels, disease activity,
      and damage indexes. We also found a positive correlation between autophagy
      enhancement and the increased salivary gland expression of IL-21 and IL-23,
      providing a further link between innate and adaptive immune responses in pSS.
      CONCLUSIONS: These findings suggest that CD4+ T lymphocyte autophagy could play a
      key role in pSS pathogenesis. Additionally, our data highlight the potential
      exploitation of T cell autophagy as a biomarker of disease activity and provide
      new ground to verify the therapeutic implications of autophagy as an innovative
      drug target in pSS.

PMID- 28743287
TI  - Genome-wide DNA methylation profile analysis identifies differentially methylated
      loci associated with ankylosis spondylitis.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune
      disease. Little is known about the potential role of DNA methylation in the
      pathogenesis of AS. This study was undertaken to explore the potential role of
      DNA methylation in the genetic mechanism of AS. METHODS: In this study, we
      compared the genome-wide DNA methylation profiles of peripheral blood mononuclear
      cells (PBMCs) between five AS patients and five healthy subjects, using the
      Illumina Infinium HumanMethylation450 BeadChip. Quantitative real-time reverse
      transcription-polymerase chain reaction (qRT-PCR) was performed to validate the
      relevance of the identified differentially methylated genes for AS, using another
      independent sample of five AS patients and five healthy subjects. RESULTS:
      Compared with healthy controls, we detected 1915 differentially methylated CpG
      sites mapped to 1214 genes. The HLA-DQB1 gene achieved the most significant
      signal (cg14323910, adjusted P = 1.84 * 10-6, beta difference = 0.5634) for AS.
      Additionally, the CpG site cg04777551 of HLA-DQB1 presented a suggestive
      association with AS (adjusted P = 1.46 * 10-3, beta difference = 0.3594). qRT-PCR
      observed that the mRNA expression level of HLA-DQB1 in AS PBMCs was significantly
      lower than that in healthy control PBMCs (ratio = 0.48 +/- 0.10, P < 0.001). Gene
      Ontology (GO) and KEGG pathway enrichment analysis of differentially methylated
      genes identified four GO terms and 10 pathways for AS, functionally related to
      antigen dynamics and function. CONCLUSIONS: Our results demonstrated the altered
      DNA methylation profile of AS and implicated HLA-DQB1 in the development of AS.

PMID- 28743288
TI  - The patient perspective: utilizing focus groups to inform care coordination for
      high-risk medicaid populations.
AB  - BACKGROUND: Care coordination programs for high-risk, high-cost patients are a
      critical component of population health management. These programs aim to improve
      outcomes and reduce costs and have proliferated over the last decade. Some
      programs, originally designed for Medicare patients, are now transitioning to
      also serve Medicaid populations. However, there are still gaps in the
      understanding of what barriers to care Medicaid patients experience, and what
      supports will be most effective for providing them care coordination. METHODS: We
      conducted two focus groups (n = 13) and thematic analyses to assess the outcomes
      drivers and programmatic preferences of Medicaid patients enrolled in a high-risk
      care coordination program at a major academic medical center in Boston, MA.
      FINDINGS: Two focus groups identified areas where care coordination efforts were
      having a positive impact, as well as areas of unmet needs among the Medicaid
      population. Six themes emerged from the focus groups that clustered in three
      groupings: In the first group (1) enrollment in an existing medical care
      coordination programs, and (2) provider communication largely presented as
      positive accounts of assistance, and good relationships with providers, though
      participants also pointed to areas where these efforts fell short. In the second
      group (3) trauma histories, (4) mental health challenges, and (5) executive
      function difficulties all presented challenges faced by high-risk Medicaid
      patients that would likely require redress through additional programmatic
      supports. Finally, in the third group, (6) peer-to-peer support tendencies among
      patients suggested an untapped resource for care coordination programs.
      CONCLUSIONS: Programs aimed at high-risk Medicaid patients will want to consider
      programmatic adjustments to attend to patient needs in five areas: (1) provider
      connection/care coordination, (2) trauma, (3) mental health, (4) executive
      function/paperwork and coaching support, and (5) peer-to-peer support.

PMID- 28743289
TI  - Inhibition of T cell-mediated inflammation in uveitis by a novel anti-CD3
      antibody.
AB  - BACKGROUND: A novel anti-mouse CD3epsilon antibody, Dow2, recognizes mouse
      CD3epsilon without activating T cells and suppresses T-cell activation. The
      purpose of this study was to determine whether Dow2 can inhibit T cells in
      uveitis. METHODS: Experimental autoimmune uveitis (EAU) was induced in mice by
      immunization with retinal peptides, followed by administration of Dow2.
      Inflammation was evaluated by color fundus photography, optical coherence
      tomography, fluorescein angiography, and histology. Intraocular cells from EAU
      mice were used to examine the effect of Dow2 on retinal antigen-specific T cells.
      The effects of Dow2, conventional CD3epsilon antibodies, and isotype control
      immunoglobulin G (IgG) on splenic T cells were compared by assessing cell
      proliferation by the mixed lymphocyte reaction assay, inflammatory cytokine
      production by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry,
      and gene expression by quantitative reverse-transcription polymerase chain
      reaction (RT-PCR). T-cell subpopulations were characterized by flow cytometry to
      evaluate the expression of CD4, CD8, CD44, CD62L, and Foxp3. RESULTS: Dow2
      significantly reduced T-cell activation and counteracted activation associated
      with anti-CD3epsilon antibodies. Unlike conventional CD3epsilon antibodies, Dow2
      treatment did not upregulate T helper (Th)1-/Th17-associated gene expression and
      cytokine production in splenic T cells. Interferon (IFN)-gamma production by
      retinal antigen-specific T cells was also significantly reduced. Ocular
      inflammation was significantly reduced in Dow2-treated EAU mice compared to
      control EAU mice, with fewer T cells infiltrating into the retinas of Dow2
      treated EAU mice. In immunohistochemistry, Th1 and Th17 cells invaded the retina
      in control EAU mice but not Dow2-treated EAU mice. No effects on peripheral T
      cell numbers were observed following systemic administration of Dow2. CONCLUSION:
      The novel anti-CD3 antibody Dow2 can inhibit T cell-mediated inflammation in
      uveitis models. Thus, inhibition of T-cell activation by anti-CD3 therapy with
      this new antibody may protect uveitis patients from severe ocular inflammation.

PMID- 28743290
TI  - Pneumatosis intestinalis with a benign clinical course: a report of two cases.
AB  - BACKGROUND: Pneumatosis intestinalis (PI) is a rare condition characterized by
      the presence of gas within the gastrointestinal tract wall. Most cases of PI have
      a benign clinical course, although some have serious outcomes. Mechanical stress
      on or bacterial infection of the gastrointestinal tract wall may be responsible
      for the onset of PI, but the detailed mechanism of PI pathogenesis is still
      unclear. Here, we describe two Japanese patients presenting with benign PI. CASE
      PRESENTATION: Case 1, a 37-year-old previously healthy male patient, had a 1-week
      history of abdominal pain, and case 2, a 78-year-old female diabetic patient, had
      a 2-week history of voglibose treatment and abdominal pain. Intramural gas was
      mainly distributed in the colon in case 1 and in the small intestine in case 2.
      Interestingly, neither patient showed obvious inflammatory signs upon admission
      and recovered spontaneously with conservative treatment, including fasting and
      fluid infusion without antibiotics. Voglibose treatment was terminated in case 2.
      Recent studies have shown the presence of nonpathogenic bacteria, such as
      Clostridium spp., in PI lesions, which usually play an important role in
      modulating the tolerance of the gastrointestinal immune responses. The benign
      clinical course and spontaneous resolution of PI in these patients, without
      specific treatment, suggests that nonpathogenic indigenous bacteria in the
      gastrointestinal tract participate in the pathogenesis of PI. CONCLUSION: In
      patients with benign PI, the absence of an inflammatory response and the
      spontaneous resolution of the disease without specific treatment suggest the
      participation of nonpathogenic indigenous bacteria of the gastrointestinal tract.

PMID- 28743291
TI  - Theory based interventions for caries related sugar intake in adults: systematic
      review.
AB  - BACKGROUND: Theories of behavior change are essential in the design of effective
      behaviour change strategies. No studies have assessed the effectiveness of
      interventions based on psychological theories to reduce sugar intake related to
      dental caries. The study assessed the effect of interventions based on Social
      Congition Models (SCMs) on sugar intake in adults, when compared with educational
      interventions or no intervention. METHODS: A range of papers were considered:
      Systematic review Systematic Reviews with or without Meta Analyses; Randomised
      Controlled Trials; Controlled Clinical Trials and Before and after studies, of
      interventions based on Social Cognition Models aimed at dietary intake of sugar
      in adults. The Cochrane database including: Oral Health Group's Trials Register
      (2015), MEDLINE (from 1966 to September 2015), EMBASE (from 1980 to September
      2015), PsycINFO (from 1966 to September 2015) were searched. RESULTS: No article
      met the full eligibility criteria for the current systematic review so no
      articles were included. CONCLUSION: There is a need for more clinical trials to
      assess the effectiveness of interventions based on psychological theory in
      reducing dietary sugar intake among adults. SYSTEMATIC REVIEW PROTOCOL
      REGISTRATION: PROSPERO: CRD42015026357 .

PMID- 28743292
TI  - Targeted designed variants of alpha-2-macroglobulin (A2M) attenuate cartilage
      degeneration in a rat model of osteoarthritis induced by anterior cruciate
      ligament transection.
AB  - BACKGROUND: The study was performed to evaluate whether targeted alpha-2
      macroglobulin (A2M) variants have a similar or enhanced function at wild-type
      (wt)-A2M to attenuate cartilage degeneration in vivo. METHODS: In and ex-vivo
      experiment, bovine cartilage explants (BCE) were incubated with TNF-alpha and IL
      1beta with or without wt-A2M or A2M variants. Cartilage catabolism was measured
      in culture supernatant by sulfated glycosaminoglycan (sGAG). In an in-vivo
      experiment, 2-month-old male Wistar rats (n = 77) were randomly divided into
      seven groups and treated with different doses of A2M or its variants by intra
      articular injection at 24 hours and day 14 after anterior cruciate ligament
      transection (ACLT), receiving (1) ACLT/PBS; (2) ACLT/wt-A2M (0.153 mg); (3)
      ACLT/CYT-108 A2M (0.153 mg); (4) ACLT/CYT-108 A2M (0.077 mg); (5) ACLT/CYT-98 A2M
      (0.153 mg); (6) ACLT/CYT-98 A2M (0.077 mg); or (7) sham/PBS. The joints and
      synovial lavage were collected 8 weeks after surgery. Fluorescence molecular
      tomography was used to monitor inflammation in vivo using probes ProSense and
      MMPSense at 24 hours, and weeks 2, 4, and 6 after surgery. The cartilage damage
      was quantified using Osteoarthritis Research Society International score and
      matrix metalloproteinase (MMP)-3, -13, collagen (Col) X, Col 2, Runx2, and
      aggrecan (Acan) were detected by immunohistochemical analysis (IHC), ELISA, and
      RT-PCR. RESULTS: A2M variants inhibited catabolism in the BCE model by up to 200%
      compared with wt-A2M. ProSense and MMPSense were dramatically increased in all
      groups after surgery. Supplemental A2M or its variants reduced ProSense and
      MMPSense compared with the PBS treatment. Less cartilage damage, lower MMP-13 and
      Col 2 degraded product, and stronger Col 2 synthesis were detected in animals
      treated with A2M or its variants compared with PBS-treated animals. A2M and its
      variants enhanced Col 2 and Acan synthesis, and suppressed MMP-3, MMP-13, Runx2,
      and Col X production. A2M-108 variant demonstrated less cartilage damage compared
      with wt-A2M and A2M-98 variant. CONCLUSION: The targeted variants of A2M have a
      chondroprotective effect similar to wt-A2M. However, A2M-108 variant has enhanced
      function to attenuate cartilage degeneration compared with wt-A2M.

PMID- 28743293
TI  - Assessment of inhaled corticosteroids use and associated factors among asthmatic
      patients attending Tikur Anbessa Specialized Hospital, Ethiopia.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) are cornerstone therapy for persistent
      asthma. However, underutilization of ICSs is common and little is known about
      factors contributing toward this undesirable use. METHODS: A cross-sectional
      study was conducted through interview and chart review among persistent asthmatic
      patients attending chest clinic of Tikur Anbessa Specialized Hospital from 1 May
      to 31 September 2014. A total of 131 eligible patients who attended the clinic
      during study period were included in the study. A multivariate logistic
      regression was used to examine the association between independent and dependent
      variables. RESULTS: Overall, extent of underutilization of ICSs was found to be
      68%. Monthly income, comorbidity and types of ICSs products prescribed showed
      significant association with reported underutilization. Patients' reported
      reasons for underutilization includes; unaffordability (44%), using only when
      symptoms exacerbate (21%), fear of side effects (10%), practitioners'
      recommendation (10%) and unavailability of ICSs in the local market (7%).
      Physicians also stated unaffordability, fear of side effects and dependency, lack
      of local guideline for asthma management and unavailability of ICSs as the
      contributing factors. CONCLUSION: In this setting, extent of underutilization of
      ICSs was found to be high and seems the result of complex interaction of various
      factors. Financial problem combined with inconsistent availability of ICSs in the
      local market, patients' poor knowledge of asthma and ICSs, negative attitude
      toward ICSs, absence of local guidelines for asthma management are found to be
      essential elements dictating an extent of ICSs use.

PMID- 28743294
TI  - Evaluation of pharmacotherapy complexity in residents of long-term care
      facilities: a cross-sectional descriptive study.
AB  - BACKGROUND: Polypharmacy is a reality in long-term care facilities. However,
      number of medications used by the patient should not be the only predictor of a
      complex pharmacotherapy. Although the level of complexity of pharmacotherapy is
      considered an important factor that may lead to side effects, there are few
      studies in this field. The aim of this study was to evaluate the complexity of
      pharmacotherapy in residents of three long-term care facilities. METHODS: A cross
      sectional study was performed to evaluate the complexity of pharmacotherapy using
      the protocols laid out in the Medication Regimen Complexity Index instrument in
      three long-term care facilities in northeastern Brazil. As a secondary result,
      potential drug interactions, potentially inappropriate medications, medication
      duplication, and polypharmacy were evaluated. After the assessment, the
      association among these variables and the Medication Regimen Complexity Index was
      performed. RESULTS: In this study, there was a higher prevalence of women (64.4%)
      with a high mean age among the study population of 81.8 (+/-9.7) years. The
      complexity of pharmacotherapy obtained a mean of 15.1 points (+/-9.8), with a
      minimum of 2 and a maximum of 59. The highest levels of complexity were
      associated with dose frequency, with a mean of 5.5 (+/-3.6), followed by
      additional instructions of use averaging 4.9 (+/-3.7) and by the dosage forms
      averaging 4.6 (+/-3.0). CONCLUSIONS: The present study evaluated some factors
      that complicate the pharmacotherapy of geriatric patients. Although polypharmacy
      was implicated as a factor directly related to complexity, other indicators such
      as drug interactions, potentially inappropriate medications, and therapeutic
      duplication can also make the use of pharmacotherapy in such patients more
      difficult.

PMID- 28743295
TI  - Group cognitive remediation therapy for younger adolescents with anorexia
      nervosa: a feasibility study in a Japanese sample.
AB  - OBJECTIVE: Cognitive remediation therapy (CRT) aims to increase patients'
      cognitive flexibility by practicing new ways of thinking as well as facilitating
      bigger picture thinking, supporting patients with relevant tasks and encouraging
      an awareness of their own thinking styles. CRT has been applied in the treatment
      of adult anorexia nervosa (AN), and has been shown to be effective and
      acceptable. In adolescents, CRT has been piloted on both individual and group
      format. However, no studies are published in CRT for adolescents with AN in a
      Japanese sample. The objectives of this study were to assess the feasibility, to
      estimate effect sizes for the purpose of designing a larger study, and to assess
      the acceptability of a CRT group for younger adolescents with AN in a Japanese
      sample. METHODS: Group CRT interventions were carried out with a total of seven
      adolescents with AN. Neuropsychological and psychological assessments
      (motivation, self-efficacy and depression) were administered before and after the
      group intervention. The participants completed worksheets (documents of
      participants' thinking about their thinking style and the relation of the skills
      that they learnt through each session to real-life) and questionnaires after the
      group. RESULTS: There were small effect sizes differences between the part of the
      pre and post neuropsychological tests and the pre and post ability to change
      (motivation). There were medium effect sizes differences between the pre and post
      depressive symptoms and importance to change (motivation). There was a large
      effect size shown between the pre and post weights. All participants were able to
      reflect on their own thinking styles, such as having difficulty with changing
      feelings and the tendency to focus on details in real-life. Adolescents' feedback
      was positive, and the rate of dropout was low. CONCLUSION: CRT groups could be
      feasible and acceptable for younger adolescents with AN in a Japanese sample.
      Trial registration UMIN No. 000020623. Registered 18 January 2016.

PMID- 28743296
TI  - Case report of hypnic headache: a rare headache disorder with nocturnal symptoms.
AB  - BACKGROUND: Headache is one of the commonest complaints reported to physicians
      worldwide. Yet, arriving at the proper diagnosis can be a challenge in many
      patients. Although most headaches belong to common categories of migraine and
      tension-type headache, which are diagnosed and managed relatively easily, several
      uncommon headache disorders can lead to delays in diagnosis. Certain medications
      are more efficacious than others in managing these headache disorders, hence
      establishing the correct diagnosis is of paramount importance. CASE PRESENTATION:
      An 86-year-old female presented with chronic daily headache of 1 year duration.
      Her headaches were exclusively nocturnal and woke her up daily around midnight.
      Clinical examination was unremarkable. All basic investigations were normal.
      Subsequent gadolinium enhanced Magnetic Resonance Imaging (MRI) brain did not
      show any significant pathology. There was no satisfactory response to
      paracetamol, diclofenac sodium, mefenamic acid, tramadol, flunarizine and sodium
      valproate. Indomethacin was started with the provisional diagnosis of hypnic
      headache. There was absolute response by day 3 of indomethacin. She remains
      headache free on low dose indomethacin maintenance at 1 year after the diagnosis.
      CONCLUSION: Better understanding of uncommon headache syndromes can help in early
      diagnosis and appropriate treatment. Hypnic headache should be considered in the
      differential diagnosis of chronic daily headaches, especially when nocturnal and
      occurs during sleep.

PMID- 28743297
TI  - Identification of reference miRNAs in plasma useful for the study of oestrogen
      responsive miRNAs associated with acquired Protein S deficiency in pregnancy.
AB  - BACKGROUND: Accumulating evidence indicate that circulating microRNAs (miRNAs)
      are useful independent non-invasive biomarkers, with unique miRNA signatures
      defined for various pathophysiological conditions. However, there are no
      established universal housekeeping miRNAs for the normalisation of miRNAs in body
      fluids. We have previously identified an oestrogen-responsive miRNA, miR-494, in
      regulating the anticoagulant, Protein S, in HuH-7 liver cells. Moreover,
      increased thrombotic risk associated with elevated circulating oestrogen levels
      is frequently observed in pregnant women and oral contraceptive users. In order
      to identify other oestrogen-responsive miRNAs, including miR-494, that may be
      indicative of increased thrombotic risk in plasma, we used nanoString analysis to
      identify robust and stable endogenous reference miRNAs for the study of oestrogen
      responsive miRNAs in plasma. RESULTS: We compared the plasma miRNA expression
      profile of individuals with: (1) Low circulating oestrogens (healthy men and non
      pregnant women not taking oral contraceptives), (2) High circulating synthetic
      oestrogens, (women taking oral contraceptives) and (3) High circulating natural
      oestrogens (pregnant females >14 weeks gestation). From the nanoString analyses,
      11 candidate reference miRNAs which exhibited high counts and not significantly
      differentially expressed between groups were selected for validation using
      realtime quantitative polymerase chain reaction (RT-qPCR) and digital droplet PCR
      (DDPCR) in pooled plasma samples, and the stability of their expression evaluated
      using NormFinder and BestKeeper algorithms. Four miRNAs (miR-25-5p, miR-188-5p,
      miR-222-3p and miR-520f) demonstrated detectable stable expression between groups
      and were further analysed by RT-qPCR in individual plasma samples, where miR-188
      5p and miR-222-3p expression were identified as a stable pair of reference genes.
      The miRNA reference panel consisting of synthetic spike-ins cel-miR-39 and ath
      miR159a, and reference miRNAs, miR-188-5p and miR-222-3p was useful in evaluating
      fold-change of the pregnancy-associated miRNA, miR-141-3p, between groups.
      CONCLUSION: The miRNA reference panel will be useful for normalising qPCR data
      comparing miRNA expression between men and women, non-pregnant and pregnant
      females, and the potential effects of endogenous and synthetic oestrogens on
      plasma miRNA expression.

PMID- 28743298
TI  - R-spondin2, a novel target of NOBOX: identification of variants in a cohort of
      women with primary ovarian insufficiency.
AB  - BACKGROUND: R-spondin2 (Rspo2) is a secreted agonist of the canonical Wnt/beta
      catenin signaling pathway. Rspo2 plays a key role in development of limbs, lungs
      and hair follicles, and more recently during ovarian follicle development. Rspo2
      heterozygous deficient female mice become infertile around 4 months of age
      mimicking primary ovarian insufficiency (POI). The study aimed to investigate the
      regulation of RSPO2 and its potential involvement in pathophysiology of POI.
      METHODS: We cloned the RSPO2 promoter and performed transcriptional assays to
      determine if RSPO2 can be regulated by NOBOX, an ovarian transcription factor.
      Then, we evaluated 100 infertile women after obtaining a detailed history of the
      disease and follicle-stimulating hormone measurements, besides karyotype
      determination and fragile-X premutation syndrome investigation. All exons, intron
      exon boundaries and untranslated regions of the RSPO2 gene were identified by
      sequencing, and the results were statistically analyzed. RESULTS: We found that
      RSPO2 can be regulated by NOBOX via the presence of NOBOX Binding Element in its
      promoter. Among 9 identified variants in POI women, 4 of them were equally
      homozygous, 4 have never been described (c.-359C > G, c.-190G > A, c.-170 + 13C >
      T and c.-169-8 T > A), only one c.557 T > C was predicted to alter a single amino
      acid in the RSPO2 protein (p.Leu186Pro). CONCLUSIONS: RSPO2 is a novel target
      gene of the NOBOX key transcription factor, confirming its important role during
      the follicular growth in ovary. However, RSPO2 mutations are rare or uncommon in
      women with POI.

PMID- 28743299
TI  - The public health value of vaccines beyond efficacy: methods, measures and
      outcomes.
AB  - BACKGROUND: Assessments of vaccine efficacy and safety capture only the minimum
      information needed for regulatory approval, rather than the full public health
      value of vaccines. Vaccine efficacy provides a measure of proportionate disease
      reduction, is usually limited to etiologically confirmed disease, and focuses on
      the direct protection of the vaccinated individual. Herein, we propose a broader
      scope of methods, measures and outcomes to evaluate the effectiveness and public
      health impact to be considered for evidence-informed policymaking in both pre-
      and post-licensure stages. DISCUSSION: Pre-licensure: Regulatory concerns dictate
      an individually randomised clinical trial. However, some circumstances (such as
      the West African Ebola epidemic) may require novel designs that could be
      considered valid for licensure by regulatory agencies. In addition, protocol
      defined analytic plans for these studies should include clinical as well as
      etiologically confirmed endpoints (e.g. all cause hospitalisations, pneumonias,
      acute gastroenteritis and others as appropriate to the vaccine target), and
      should include vaccine-preventable disease incidence and 'number needed to
      vaccinate' as outcomes. Post-licensure: There is a central role for phase IV
      cluster randomised clinical trials that allows for estimation of population-level
      vaccine impact, including indirect, total and overall effects. Dynamic models
      should be prioritised over static models as the constant force of infection
      assumed in static models will usually underestimate the effectiveness and cost
      effectiveness of the immunisation programme by underestimating indirect effects.
      The economic impact of vaccinations should incorporate health and non-health
      benefits of vaccination in both the vaccinated and unvaccinated populations, thus
      allowing for estimation of the net social value of vaccination. CONCLUSIONS: The
      full benefits of vaccination reach beyond direct prevention of etiologically
      confirmed disease and often extend across the life course of a vaccinated person,
      prevent outcomes in the wider community, stabilise health systems, promote health
      equity, and benefit local and national economies. The degree to which
      vaccinations provide broad public health benefits is stronger than for other
      preventive and curative interventions.

PMID- 28743300
TI  - Public attitudes towards gambling product harm and harm reduction strategies: an
      online study of 16-88 year olds in Victoria, Australia.
AB  - BACKGROUND: Gambling has quickly emerged as an important global public health
      issue. With new technologies used to develop high intensity gambling products and
      promotions aimed at driving consumption, public health organisations and
      researchers, community groups, and politicians have argued for a range of
      regulatory and education measures aimed at reducing gambling harm. However, there
      has been limited research seeking to understand community perceptions of the
      harms associated with gambling products and environments, and the level of
      community support for strategies designed to prevent and reduce gambling harm.
      METHODS: An online study of 500 adolescents and adults (aged 16 and over) was
      conducted with a representative sample (by age and gender) of individuals who
      were current residents in the state of Victoria, Australia. Participants were
      asked a range of questions about their own gambling behaviours, with the Problem
      Gambling Severity Index (PGSI) used as a measure of problem gambling.
      Participants were asked about their perceptions of harms associated with
      electronic gambling machines (EGMs), sports betting, horse betting, and casino
      gambling. They were also asked about the extent to which they agreed or disagreed
      with gambling harm reduction strategies related to marketing and promotions,
      restrictions on gambling products and venues, and public education campaigns.
      Quantitative data were analysed using descriptive statistics and paired t tests,
      with thematic analysis used to interpret qualitative responses to open-ended
      questionnaire items. RESULTS: More than one third (n = 201, 40.2%) of
      participants were at risk of experiencing some level of harm from gambling (PGSI
      >= 1), with 83 participants (16.6%) recording scores that indicated problem
      gambling (PGSI >= 8). One in five participants gambled on EGMs at least monthly
      (n = 100, 20.0%). Those who gambled on sports did so frequently, with nearly 1 in
      5 gambling on sport at least once a month (n = 87, 17.4%). Over half of the
      sample rated casino gambling and EGMs as very harmful, while one third rated
      these forms of gambling as extremely harmful. Over one third of the sample rated
      horse and sports betting as very harmful, with one in five rating these products
      as extremely harmful. There was strong agreement with the need to ban gambling
      advertising during children's viewing hours, during sporting matches and at
      sporting venues. The majority of participants agreed with reducing and
      restricting EGMs, and providing more public education for both adults and
      children about the negative consequences from gambling. CONCLUSIONS: The findings
      suggest a strong perception in the Victorian community that gambling products are
      harmful. While governments have been reluctant to implement a comprehensive
      approach to reducing gambling harm, this study reveals significant community
      support for a range of harm reduction and prevention measures associated with
      gambling products. Public health practitioners can use this evidence in
      advocating for a comprehensive public health approach to reducing the harms
      associated with gambling promotions and products.

PMID- 28743301
TI  - Loading pattern of postoperative hallux valgus feet with and without transfer
      metatarsalgia: a case control study.
AB  - BACKGROUND: Postoperative transfer metatarsalgia is a common complication after
      hallux valgus surgeries. Shortening of the first metatarsal is traditionally
      thought to be the primary cause of it. However, we speculate the abnormal loading
      pattern during gait is the real reason. This study is to determine specific
      differences in the loading patterns between reconstructive hallux valgus (HV)
      feet with and without postoperative transfer metatarsalgia, so as to find risky
      loading characteristics of this complication. METHODS: Thirty feet with
      postoperative transfer metatarsalgia were recruited as pain group, while another
      30 postoperative feet without pain as controls. All participants were asked to
      walk barefoot at self-selected speed through a plantar force measuring plate (Rs
      Scan Inc.) for three times. Certain plantar load variables were recorded or
      calculated, and their differences between two groups were compared. RESULTS: For
      pain group, the maximum plantar force and force time integral of the first
      metatarsal decrease significantly; the force time integral of the central rays
      (second plus third metatarsal) does not significantly differ with that in the
      controls, but their cumulative load percentage to the whole foot is higher. In
      pain group, the time point when central rays reached their peak force during the
      push-off is significantly later than that in controls. And the regional instant
      load percentage at this moment presented significantly higher for central rays,
      while significantly lower for the first metatarsal and the hallux compared to the
      controls. CONCLUSIONS: For hallux valgus feet with postoperative metatarsalgia,
      the load function of the first metatarsal is obviously impaired. But for central
      rays, indicative difference is not reflected in either peak or cumulative load
      during the gait cycle, but in the instant load distribution when central rays
      reach their peak load. So we can conclude that whether the remaining regions can
      adequately share certain load during walking, especially around the time
      metatarsalgia often occurs, plays an unnegligible role. So surgeons should pay
      more attention to reconstruct a foot where load can be evenly distributed.

PMID- 28743302
TI  - Cognition, culture and utility: plant classification by Paraguayan immigrant
      farmers in Misiones, Argentina.
AB  - BACKGROUND: This study was conducted in three rural communities of small farmers
      of Paraguayan origin living in the province of Misiones, Argentina. These
      Criollos (Mestizos) hail chiefly from departments located in the east of
      Paraguay, where the climate and flora have similar characteristics as those in
      Misiones. These ecological features contribute to the continuation and
      maintenance of knowledge and practices related to the use of plants. METHODS:
      Fieldwork was conducted between September 2014 and August 2015. Forty five
      informants from three rural localities situated along the Parana River
      participated in an ethno-classification task. For the classification event,
      photographs of 30 medicinal and edible plants were chosen, specifically those
      yielding the highest frequency of mention among the members of that community
      (based on data obtained in the first stage of research in 2014). Variation in
      local plant classifications was examined and compared using principal component
      analysis and cluster analysis. RESULTS: We found that people classify plants
      according to application or use (primarily medicinal, to a lesser extent as
      edible). Morphology is rarely taken into account, even for very similar and
      closely-related species such as varieties of palms. In light of our findings, we
      highlight a dominant functionality model at work in the process of plant
      cognition and classification among farmers of Paraguayan origin. Salient cultural
      beliefs and practices associated with rural Paraguayan plant-based medicine are
      described. Additionally, the manner by which residents' concepts of plants
      articulate with local folk epistemology is discussed. CONCLUSIONS: Culturally
      constructed use patterns ultimately override morphological variables in rural
      Paraguayans' ethnobotanical classification.

PMID- 28743303
TI  - Multiorgan eosinophilic infiltration after initiation of clozapine therapy: a
      case report.
AB  - BACKGROUND: The eosinophilic response to clozapine is well described in the
      literature, causing a variety of responses, from serositis to colitis. However,
      there are not case reports describing a clozapine-induced marked eosinophilia
      resulting in multiorgan dysfunction. CASE PRESENTATION: In this case report, we
      describe a 24 year old Caucasian male who presented with severe systemic
      eosinophilia resulting in eosinophilic GI tract infiltration, myocarditis,
      pericardial and pleural effusions with dramatic improvement following drug
      withdrawal. CONCLUSIONS: Clozapine associated eosinophilia should be suspected in
      the setting of eosinophilic infiltration of multiple organs.

PMID- 28743304
TI  - Running on a high: parkrun and personal well-being.
AB  - BACKGROUND: Sporting or physical recreation event participation can affect
      different domains of mental and social well-being if sufficiently frequent, yet
      previous research has focused mainly on the physical health benefits of single
      location or infrequent mass-participation events. We examined overall and domain
      specific subjective well-being of adult participants of "parkrun", a weekly,
      community-based, highly accessible and widespread running event. METHODS: Data
      were from a national online survey of 865 adult Australian parkrunners. Scores on
      nine individual measures and the global Personal Well-being Index (PWI) were
      compared to national, normative data. Regression models tested associations
      between personal well-being and perceived benefits of parkrun (mental health and
      connection to community). RESULTS: Of 100 scores, 28% of means for parkrunners
      fell outside overall and age and gender subgroups normative ranges. Satisfaction
      with health was higher for male, those aged over 45 and overall parkrunners; only
      parkrunners aged 18-24 fell below their age group norm. Satisfaction with life as
      a whole was positively associated with perceived mental health benefits of
      parkrun, but not perceived community connection for women, and neither measure
      for men. PWI was positively associated with perceived community connection for
      men and with mental health benefit for women. CONCLUSIONS: Australian parkrunners
      mostly reflect the general population on personal well-being, except report
      superior satisfaction with physical health. Women's personal well-being may
      benefit from parkrun through improved mental health and men's from community
      connectedness. parkrun may facilitate positive expression of identity and
      continuation of healthy habits among athletes, and non-demanding, health
      enhancing activity and social interaction for non-athletes.

PMID- 28743305
TI  - Prognosis and longitudinal changes of physical activity in idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: Physical activity (PA) is associated with disease severity in
      idiopathic pulmonary fibrosis (IPF), but longitudinal studies evaluating its
      prognostic value and changes over time are lacking. METHODS: We measured PA
      (steps per day, SPD) in a cohort of 46 IPF-patients (mean age, 67 years; mean
      FVC, 76.1%pred.) by accelerometry at baseline, recorded survival status during 3
      years follow-up and repeated measurements in survivors. We compared the
      prognostic value of PA to established mortality predictors including lung
      function (FVC, DLCO) and 6-min walking-distance (6MWD). RESULTS: During follow-up
      (median 34 months) 20 patients (43%) died. SPD and FVC best identified non
      survivors (AUROC-curve 0.79, p < 0.01). After adjustment for confounders (sex,
      age, therapy), a standardized increase (i.e. one SD) in SPD, FVC%pred. or
      DLCO%pred. was associated with a more than halved risk of death (HR < 0.50; p <
      0.01). Compared to baseline, SPD, FVC, and 6MWD annually declined in survivors by
      973 SPD, 130 ml and 9 m, resulting in relative declines of 48.3% (p < 0.001),
      13.3% (p < 0.001) and 7.8% (p = 0.055), respectively. CONCLUSION: While PA
      predicts mortality of IPF patients similar to established functional measures,
      longitudinal decline of PA seems to be disproportionally large. Our data suggest
      that the clinical impact of disease progression could be underestimated by
      established functional measures.

PMID- 28743306
TI  - Detection of 22 common leukemic fusion genes using a single-step multiplex qRT
      PCR-based assay.
AB  - BACKGROUND: Fusion genes generated from chromosomal translocation play an
      important role in hematological malignancies. Detection of fusion genes currently
      employ use of either conventional RT-PCR methods or fluorescent in situ
      hybridization (FISH), where both methods involve tedious methodologies and
      require prior characterization of chromosomal translocation events as determined
      by cytogenetic analysis. In this study, we describe a real-time quantitative
      reverse transcription PCR (qRT-PCR)-based multi-fusion gene screening method with
      the capacity to detect 22 fusion genes commonly found in leukemia. This method
      does not require pre-characterization of gene translocation events, thereby
      facilitating immediate diagnosis and therapeutic management. METHODS: We
      performed fluorescent qRT-PCR (F-qRT-PCR) using a commercially-available multi
      fusion gene detection kit on a patient cohort of 345 individuals comprising 108
      cases diagnosed with acute myeloid leukemia (AML) for initial evaluation;
      remaining patients within the cohort were assayed for confirmatory diagnosis.
      Results obtained by F-qRT-PCR were compared alongside patient analysis by
      cytogenetic characterization. RESULTS: Gene translocations detected by F-qRT-PCR
      in AML cases were diagnosed in 69.4% of the patient cohort, which was
      comparatively similar to 68.5% as diagnosed by cytogenetic analysis, thereby
      demonstrating 99.1% concordance. Overall gene fusion was detected in 53.7% of the
      overall patient population by F-qRT-PCR, 52.9% by cytogenetic prediction in
      leukemia, and 9.1% in non-leukemia patients by both methods. The overall
      concordance rate was calculated to be 99.0%. Fusion genes were detected by F-qRT
      PCR in 97.3% of patients with CML, followed by 69.4% with AML, 33.3% with acute
      lymphoblastic leukemia (ALL), 9.1% with myelodysplastic syndromes (MDS), and 0%
      with chronic lymphocytic leukemia (CLL). CONCLUSIONS: We describe the use of a F
      qRT-PCR-based multi-fusion gene screening method as an efficient one-step
      diagnostic procedure as an effective alternative to lengthy conventional
      diagnostic procedures requiring both cytogenetic analysis followed by targeted
      quantitative reverse transcription (qRT-PCR) methods, thus allowing timely
      patient management.

PMID- 28743307
TI  - Hemoglobin Himeji and inconsistent hemoglobin A1c values: a case report.
AB  - BACKGROUND: Hemoglobin A1c is used to evaluate the glycemic control in patients
      with diabetes and is a risk marker for chronic complications of diabetes.
      Hemoglobin variants are reported to falsely lower or increase hemoglobin A1c test
      results. We present a case report of a patient with diabetes with discrepancy
      between fasting plasma glucose and hemoglobin A1c due to the presence of
      hemoglobin Himeji, a clinically silent and very rare hemoglobinopathy. CASE
      PRESENTATION: A 76-year-old white woman, born and living in Portugal, with type 2
      diabetes presented to the family physician for a routine visit. She had no active
      complaints, including history or symptoms of hypoglycemia, and her physical
      examination was unremarkable. A review of her laboratory data showed fasting
      plasma glucose of 190 mg/dL and a hemoglobin A1c of 4.1%. The remaining blood
      test results were clinically insignificant; a further review of her laboratory
      data over the past 4 years revealed that her fasting plasma glucose had ranged
      from 130 to 250 mg/dL and hemoglobin A1c was consistently lower than 5%. A study
      of hemoglobins detected 32.8% of abnormal hemoglobin. Genetic sequencing
      identified a heterozygous mutation compatible with hemoglobin Himeji (c.422C>A;
      p.Ala141Asp). We tracked her family (three sons, six grandchildren, and two
      greatgrandchildren) for the presence of this hemoglobin variant, but none had
      this hemoglobinopathy. CONCLUSIONS: Despite the advantages of hemoglobin A1c in
      the follow-up and treatment of diabetes, the factors that interfere with its
      results must be known to ensure a correct estimation of the degree of glycemic
      control and a proper management of the disease. Therefore, health professionals
      should suspect the existence of hemoglobin variants when: the hemoglobin A1c
      value is above 15% or below the lower limit of its reference interval; there is a
      significant modification in its result coinciding with a change in assay methods;
      and there is a low correlation between plasma glucose and hemoglobin A1c. In
      patients with hemoglobin Himeji, alternate ways of monitoring glycemic control
      (fructosamine or glycated serum albumin) should be used.

PMID- 28743308
TI  - Distribution and current infection status of Biomphalaria straminea in Hong Kong.
AB  - BACKGROUND: Schistosomiasis, also generally known as snail fever, is a parasitic
      disease caused by trematode flatworms of the genus Schistosoma. In Hong Kong and
      mainland China, the freshwater snail Biomphalaria straminea has been introduced
      and has the potential to transmit intestinal schistosomiasis caused by S.
      mansoni, a parasite of man which has a wide distribution in Africa and parts of
      the New World, especially Brazil. The first identification of B. straminea in
      Hong Kong dates back to the 1970s, and its geographical distribution,
      phylogenetic relationships, and infection status have not been updated for more
      than 30 years. Thus, this study aims to reveal the distribution and current
      infection status of B. straminea in contemporary Hong Kong. METHODS: Snails were
      collected from different parts of Hong Kong from July 2016 to January 2017. Both
      anatomical and molecular methods were applied to identify B. straminea.
      Cytochrome c oxidase subunit 1 (cox1), internal transcribed spacer 1 (ITS1), 5.8S
      rDNA, internal transcribed spacer 2 (ITS2), and 16S ribosomal DNA (rDNA) were
      sequenced from individual snails and analyzed. To detect the presence of S.
      mansoni, both biopsy and PCR analyses were carried out. RESULTS: Using both
      anatomical and molecular analyses, this study demonstrated the existence of black
      and red-coloured shell B. straminea in different districts in the New
      Territories in Hong Kong, including places close to the mainland China border.
      None of the B. straminea (n = 87) investigated were found to be infected with S.
      mansoni when tested by biopsy and PCR. The Hong Kong B. straminea are genetically
      indistinguishable, based on the chosen molecular markers (cox1, ITS1-5.8S-ITS2,
      and 16S rDNA), and are similar to those obtained in mainland China and South
      America. CONCLUSION: Biomphalaria straminea is now well established in freshwater
      habitats in Hong Kong. No evidence of infection with S. mansoni has been found.
      Surveillance should be continued to monitor and better understand this
      schistosomiasis intermediate host in mainland China and Hong Kong.

PMID- 28743309
TI  - Efficient treatment of a metastatic melanoma patient with a combination of BRAF
      and MEK inhibitors based on circulating tumor DNA analysis: a case report.
AB  - BACKGROUND: Fixed tissues are the standard samples used in routine practice for
      molecular testing. But sometimes tissues are lacking or difficult to obtain. In
      these cases, circulating tumor DNA released from tumor cells can be used as an
      alternative source of tumor DNA. CASE PRESENTATION: We present the case of a 63
      year-old Caucasian woman with a metastatic melanoma and a very poor performance
      status. A plasma sample was tested and the BRAF p.V600E mutation was detected.
      Based on this result, a treatment combining a BRAF inhibitor and a MEK inhibitor
      was immediately started. This patient achieved a complete response. In addition,
      by repeating the plasma test, we could obtain a precise kinetic of release of
      mutated BRAF DNA in plasma. CONCLUSIONS: We report here for the first time the
      efficient treatment of a metastatic melanoma patient on the basis of circulating
      tumor DNA analysis. This urgent treatment provided a dramatic response in a
      patient with a very poor initial condition. The kinetic data most likely reflect
      treatment efficacy.

PMID- 28743310
TI  - The effect of frequency-specific sound signals on the germination of maize seeds.
AB  - OBJECTIVE: The effects of sound treatments on the germination of maize seeds were
      determined. RESULTS: White noise and bass sounds (300 Hz) had a positive effect
      on the germination rate. Only 3 h treatment produced an increase of about 8%, and
      5 h increased germination in about 10%. Fast-green staining shows that at least
      part of the effects of sound are due to a physical alteration in the integrity of
      the pericarp, increasing the porosity of the pericarp and facilitating oxygen
      availability and water and oxygen uptake. Accordingly, by removing the pericarp
      from the seeds the positive effect of the sound on the germination disappeared.

PMID- 28743311
TI  - Hypercapnic respiratory failure during pregnancy due to polymyositis-related
      respiratory muscle weakness: a case report.
AB  - BACKGROUND: Polymyositis is a rare medical disorder complicating pregnancy.
      Ventilatory muscle weakness leading to respiratory failure is an uncommon
      manifestation of this autoimmune disease. We report a case of life-threatening
      hypercapnic respiratory failure due to polymyositis-related respiratory muscle
      weakness in a pregnant woman. CASE PRESENTATION: A 31-year-old, African woman in
      her second trimester of pregnancy presented to the emergency department with
      fever, shortness of breath and muscle weakness. Initial investigations excluded
      pulmonary infection, thromboembolism, and cardiac dysfunction as the underlying
      cause of her symptoms. She developed deterioration in her level of consciousness
      due to carbon dioxide narcosis requiring invasive mechanical ventilation. Further
      workup revealed markedly elevated serum creatine kinase, abnormal
      electromyography and edema of her thigh muscles on magnetic resonance imaging.
      Diagnosis of polymyositis was confirmed by muscle biopsy. After receiving pulse
      steroid, intravenous immunoglobulins, and maintenance immunosuppressive therapy,
      our patient's respiratory muscle function improved and she was weaned off
      mechanical ventilation. Despite good maternal recovery from critical illness, the
      fetus developed intrauterine growth retardation and distress necessitating
      emergency cesarian section. CONCLUSIONS: New-onset polymyositis during pregnancy
      presenting with respiratory failure is rare. Early diagnosis and prompt
      initiation of therapy is necessary to improve fetal and maternal outcomes.

PMID- 28743312
TI  - Emergence of fluoroquinolone resistance among drug resistant tuberculosis
      patients at a tertiary care facility in Karachi, Pakistan.
AB  - BACKGROUND: Pakistan is classified as one of the high multi-drug resistant
      tuberculosis (MDR-TB) burden countries. A poorly regulated private sector, over
      prescription of antibiotics and self-medication has led to augmented rates of
      drug-resistance in the country. Pakistan's first national anti-tuberculosis drug
      resistance survey identified high prevalence of fluoroquinolone resistance among
      MDR-TB patients. Further institutional evidence of fluoroquinolone drug
      resistance can support re-evaluation of treatment regimens as well as invigorate
      efforts to control antibiotic resistance in the country. FINDINGS: In this study,
      data for drug-susceptibility testing (DST) was retrospectively analyzed for a
      total of 133 patients receiving MDR-TB treatment at the Chest Department of
      Jinnah Postgraduate Medical Center, Karachi, Pakistan. Frequency analyses for
      resistance patterns was carried out and association of fluoroquinolone
      (ofloxacin) resistance with demographics and past TB treatment category were
      assessed. Within first-line drugs, resistance to isoniazid was detected in 97.7%
      of cases, followed by rifampicin (96.9%), pyrazinamide (86.4%), ethambutol
      (69.2%) and streptomycin (64.6%). Within second-line drugs, ofloxacin resistance
      was detected in 34.6% of cases. Resistance to ethionamide and amikacin was 2.3%
      and 1.6%, respectively. Combined resistance of oflaxacin and isoniazid was
      detected in 33.9% of cases. Age, gender and past TB treatment category were not
      significantly associated with resistance to ofloxacin. CONCLUSION:
      Fluoroquinolone resistance was observed in an alarmingly high proportion of MDR
      TB cases. Our results suggest caution in their use for empirical management of
      MDR-TB cases and recommended treatment regimens for MDR-TB may require re
      evaluation. Greater engagement of private providers and stringent pharmacy
      regulations are urgently required.

PMID- 28743313
TI  - Behavioral weight-loss treatment plus motivational interviewing versus attention
      control: lessons learned from a randomized controlled trial.
AB  - BACKGROUND: Studies evaluating the benefit of adding motivational interviewing
      (MI) to behavioral weight-loss programs (BWLPs) have yielded mixed findings.
      METHODS: The aims of this randomized controlled trial were to: (1) assess the
      efficacy of adding MI to a BWLP on weight loss and adherence among 135
      individuals with overweight and obesity (77.8% female; mean BMI = 33.6 kg/m2)
      enrolled in a 12-week BWLP and (2) explore levels of importance, confidence, and
      readiness for change ratings. RESULTS: Participants, who were randomized to
      receive two MI sessions or two attention control sessions, were assessed at
      baseline, the end of the BWLP, and 6 months post BWLP. Both groups decreased
      their weight from baseline to the end of the BWLP; however, there was no weight
      change in either group  when measured between baseline and 6 months post BWLP. We
      observed no group differences in importance, confidence, and readiness for change
      after each session. CONCLUSIONS: We highlight some important lessons learned from
      the present trial that can be applied to MI + BWLP research. Participants may not
      have benefited from MI because they were already highly motivated to change,
      which highlights the importance of pretreatment assessment. Findings also suggest
      that treatment monitoring may help to enhance MI + BWLP efficacy by guiding a
      stepped-care approach that identifies individuals for whom additional MI sessions
      are needed, and when. A focus on refining elements of treatment remains an
      important direction. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier:
      NCT02649634 . Retrospectively registered on 5 January 2016.

PMID- 28743314
TI  - Multidrug resistant bacteria are sensitive to Euphorbia prostrata and six others
      Cameroonian medicinal plants extracts.
AB  - BACKGROUND: Multidrug resistant (MDR) bacteria are responsible for therapeutic
      failure and there is an urgent need for novels compounds efficient on them.
      METHODS: Eleven methanol extracts from seven Cameroonian medicinal plants were
      tested for their antibacterial activity using broth micro-dilution method against
      36 MDR bacterial strains including Escherichia coli, Enterobacter aerogenes,
      Enterobacter cloacae, Klebsiella pneumoniae, Providencia stuartii, Pseudomonas
      aeruginosa and Staphylococcus aureus. RESULTS: Euphorbia prostrata extract was
      found active against all the 36 tested bacteria including Gram-negative
      phenotypes over-expressing efflux pumps such as P. aeruginosa PA124, E. aerogenes
      CM64 and E. coli AG102. E. prostrata had minimal inhibitory concentrations values
      between 128 and 256 ug/mL on 55.55% of the studied microorganisms. Other plants
      extract displayed selective antibacterial activity. CONCLUSIONS: Results obtained
      in this study highlight the antibacterial potential of the tested plants and the
      possible use of E. prostrata to combat bacterial infections including MDR
      phenotypes.

PMID- 28743316
TI  - Spotted Fever Group Rickettsioses (SFGR): weather and incidence in Illinois.
AB  - The purpose of this study was to identify predictors of increasing incidence of
      Spotted Fever Group rickettsioses (SFGR) in Illinois, with a specific focus on
      weather variables. We analysed cases of SFGR reported to the Illinois Department
      of Public Health from 2004 to 2013. Surveillance definitions changed in 2008 and
      2010, but those changes alone did not account for observed spikes in incidence in
      2008, 2012 and 2013. A total of 590 cases of SFGR occurred, with the majority in
      the southernmost portion of the state. Only 3.4% of the reported cases were
      considered confirmed under the case definition. Increased mean winter temperature
      (IRR 1.32, CI 1.25-1.40) and increased precipitation (IRR 1.08, CI 1.04-1.11)
      were each associated with increased incidence of SFGR. Our findings show that
      weather appears to play a significant role in explaining the increasing annual
      incidence of SFGR in Illinois.

PMID- 28743315
TI  - Tight intra-operative blood pressure control versus standard care for patients
      undergoing hip fracture repair - Hip Fracture Intervention Study for Prevention
      of Hypotension (HIP-HOP) trial: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Hypotension during anaesthesia for hip fracture surgery is common.
      Recent data suggest that there is an association between the lowest intra
      operative blood pressure and mortality, even when adjusted for co-morbidities.
      This is consistent with data derived from the wider surgical population, where
      magnitude and duration of hypotension are associated with mortality and peri
      operative complications. However, there are no trial to data to support more
      aggressive blood pressure control. METHODS/DESIGN: We are conducting a three
      centre, randomised, double-blinded pilot study in three hospitals in the United
      Kingdom. The sample size will be 75 patients (25 from each centre). Randomisation
      will be done using computer-generated concealed tables. Both participants and
      investigators will be blinded to group allocation. Participants will be aged >70
      years, cognitively intact (Abbreviated Mental Test Score 7 or greater), able to
      give informed consent and admitted directly through the emergency department with
      a fractured neck of the femur requiring operative repair. Patients randomised to
      tight blood pressure control or avoidance of intra-operative hypotension will
      receive active treatment as required to maintain both of the following: systolic
      arterial blood pressure >80% of baseline pre-operative value and mean arterial
      pressure >75 mmHg throughout. All participants will receive standard hospital
      care, including spinal or general anaesthesia, at the discretion of the clinical
      team. The primary outcome is a composite of the presence or absence of defined
      cardiovascular, renal and delirium morbidity within 7 days of surgery (myocardial
      injury, stroke, acute kidney injury, delirium). Secondary endpoints will include
      the defined individual morbidities, mortality, early mobility and discharge to
      usual residence. DISCUSSION: This is a small-scale pilot study investigating the
      feasibility of a trial of tight intra-operative blood pressure control in a frail
      elderly patient group with known high morbidity and mortality. Positive findings
      will provide the basis for a larger-scale study. TRIAL REGISTRATION: ISRCTN
      Registry identifier: ISRCTN89812075 . Registered on 30 August 2016.

PMID- 28743317
TI  - Action of natural phytosanitary products on Bacillus thuringiensis subsp.
      kurstaki S-1905.
AB  - The objective of this study was to evaluate the effects of natural phytosanitary
      products (NPs) on spores and crystals of Bacillus thuringiensis subsp. kurstaki S
      1905 (Btk S-1905). For the spore assay, NPs and bacteria were applied in
      combination and individually. For the combined application, Btk S-1905 + NP
      mixtures were inoculated on nutrient agar (NA), and for the separate
      applications, the NPs were spread on NA plates, which were later inoculated with
      the pathogen. The number of colony-forming units (CFU) per milliliter was
      quantified after 18 h of incubation. For the crystal protein degradation assay,
      the Btk S-1905 + NP mixtures were added to the diet of Anticarsia gemmatalis
      (Lepidoptera: Erebidae), and mortality was evaluated at the following time
      points: 12, 24, 48, and 72 h. Scanning electron microscopy and agarose gel
      electrophoresis were carried out. Biogermex and Ecolife(r) reduced the CFU ml-1
      in both combined and separate applications. Biogermex, Ecolife(r), and Planta
      Clean were antagonistic to the action of bacterial toxins, and no product
      affected the morphology or resulted in the degradation of the crystal proteins.
      The remaining products evaluated did not reduce the CFU ml-1 and had additive
      effect when combined with the crystal toxin.

PMID- 28743318
TI  - Benefits of Manometer in Non-Invasive Ventilatory Support.
AB  - : Introduction Effective ventilation during cardiopulmonary resuscitation (CPR)
      is essential to reduce morbidity and mortality rates in cardiac arrest.
      Hyperventilation during CPR reduces the efficiency of compressions and coronary
      perfusion. Problem How could ventilation in CPR be optimized? The objective of
      this study was to evaluate non-invasive ventilator support using different
      devices. METHODS: The study compares the regularity and intensity of non-invasive
      ventilation during simulated, conventional CPR and ventilatory support using
      three distinct ventilation devices: a standard manual resuscitator, with and
      without airway pressure manometer, and an automatic transport ventilator.
      Student's t-test was used to evaluate statistical differences between groups. P
      values <.05 were regarded as significant. RESULTS: Peak inspiratory pressure
      during ventilatory support and CPR was significantly increased in the group with
      manual resuscitator without manometer when compared with the manual resuscitator
      with manometer support (MS) group or automatic ventilator (AV) group. CONCLUSION:
      The study recommends for ventilatory support the use of a manual resuscitator
      equipped with MS or AVs, due to the risk of reduction in coronary perfusion
      pressure and iatrogenic thoracic injury during hyperventilation found using
      manual resuscitator without manometer. Lacerda RS , de Lima FCA , Bastos LP ,
      Vinco AF , Schneider FBA , Coelho YL , Fernandes HGC , Bacalhau JMR , Bermudes
      IMS , da Silva CF , da Silva LP , Pezato R . Benefits of manometer in non
      invasive ventilatory support. Prehosp Disaster Med. 2017;32(6):615-620.

PMID- 28743319
TI  - Nationwide survey on current management strategies of toddler's fractures.
AB  - BACKGROUND: Tibial fractures are common in children less than 3 years old. The
      traditional management involves immobilization in an above knee cast for both
      confirmed (positive x-ray) and presumed (normal x-ray) toddler's fractures. This
      carries health care implications and causes unnecessary burden for patients and
      their families. There is a paucity of literature describing the ideal
      immobilization strategy for this injury. OBJECTIVES: To determine: 1) the
      variation between Canadian emergency departments in management of toddler's
      fractures; 2) the variation in management between confirmed and presumed
      toddler's fractures; 3) the association between demographic variables and
      immobilization strategies. METHODS: This was an email survey of all members of
      the Pediatric Emergency Research Canada network. The survey consisted of 2
      clinical vignettes followed by multiple-choice questions. RESULTS: Survey
      response rate was 73% (153/211). For confirmed toddler's fractures, 39% of
      physicians chose to immobilize with above knee circumferential cast, 27% with
      below knee circumferential cast and 20% with below knee splint. For presumed
      toddler's fractures, 44% of respondents chose to manage without casting, 22% with
      below knee splint and 14% with above knee circumferential cast. There was
      significant practice variation between Canadian pediatric emergency departments
      for both types of fractures and between the management of confirmed and presumed
      toddler's fractures. CONCLUSIONS: Our study is the first to identify nationwide
      variation in the management of toddler's fractures. This variation highlights the
      need for future research to compare the different management strategies to
      determine families' preferences and functional outcomes in children with these
      injuries.

PMID- 28743320
TI  - Mobility assessments of geriatric emergency department patients: A systematic
      review.
AB  - OBJECTIVES: We wished to determine the impact of emergency department (ED)
      mobility assessments for older patients on hospitalization, return visits, future
      falls, and frailty. METHODS: We searched MEDLINE, Embase, CINAHL, Cochrane
      Library, PEDro, and OTseeker (September 2016). Two independent reviewers
      identified studies of patients >=65 years with ED physical mobility assessments
      and outcomes of hospitalization, return to ED, falls, and frailty. Language was
      not restricted. Only clinical trials and observational studies were included.
      RESULTS: We identified 1,365 unique citations. Nine studies (six cohort and three
      cross-sectional) met full inclusion criteria. Patients (n=2,513) with mean age 75
      85 years, admitted to hospital and discharged, underwent these ED evaluations:
      Timed Up and Go (TUG), Get Up and Go, tandem walk, and a gait assessment. Study
      quality was moderate to poor. Tandem walk did not predict falls at 90 days. TUG
      was not associated with return to the ED/hospitalization at 90 days. Get Up and
      Go was associated with hospital admission but not return to ED visits at 1 or 3
      months. Due to clinical heterogeneity in study populations and outcomes, a meta
      analysis was not undertaken. CONCLUSIONS: Despite multiple guidelines
      recommending a mobility assessment prior to ED discharge for older patients, we
      found that such assessments were neither associated with nor predictive of
      adverse outcomes. Robust research is required to guide clinicians on the utility
      of physical mobility assessments in older ED patients.

PMID- 28743321
TI  - Disturbance induced dynamics of a tritrophic novel ecosystem.
AB  - Novel ecosystems formed by invasive plants provide a good opportunity to get
      insight into early dynamics and pattern formation of these ecosystems. The
      invasive black locust as host plant, Bruchophagus robiniae as host-specific seed
      predator and its parasitoids were the components of the studied tritrophic
      system. To investigate disturbance-driven dynamics of this system we created seed
      vacated host plant patches in a field experiment. We removed all pods from
      selected patches of black locust resulting in an induced local extinction of seed
      predators and their parasitoids. We hypothesized that disturbance enhances top
      down control by parasitoids; this enhanced top-down control decreases seed
      predation, facilitating the host plant's spread. We found that disturbance
      modified only parasitism after controlling with year effect: in vacated patches
      median parasitism was higher than in control patches. Seed predation exceeded its
      initial level in vacated patches in the third year after the disturbance, but in
      the fourth year it dropped again presumably due to the strong top-down control.
      Our findings also suggested that the seed predator was also affected by the
      bottom-up control of its host plant's density. We found that in the studied new
      ecosystem the top-down control was strengthened by the disturbance. Since the
      host plant of the tritrophic system is an invasive species, partial habitat
      disturbance of such species may increase the severity of parasitoid top-down
      control, which may reduce seed predation by the herbivores.

PMID- 28743322
TI  - Presentation of the Coding and Assessment System for Narratives of Trauma
      (CASNOT): Application in Spanish Battered Women and Preliminary Analyses.
AB  - This study introduces a new coding system, the Coding and Assessment System for
      Narratives of Trauma (CASNOT), to analyse several language domains in narratives
      of autobiographical memories, especially in trauma narratives. The development of
      the coding system is described. It was applied to assess positive and
      traumatic/negative narratives in 50 battered women (trauma-exposed group) and 50
      nontrauma-exposed women (control group). Three blind raters coded each narrative.
      Inter-rater reliability analyses were conducted for the CASNOT language
      categories (multirater Kfree coefficients) and dimensions (intraclass correlation
      coefficients). High levels of inter-rater agreement were found for most of the
      language domains. Categories that did not reach the expected reliability were
      mainly those related to cognitive processes, which reflects difficulties in
      operationalizing constructs such as lack of control or helplessness, control or
      planning, and rationalization or memory elaboration. Applications and limitations
      of the CASNOT are discussed to enhance narrative measures for autobiographical
      memories.

PMID- 28743323
TI  - Teaching diagnostic reasoning: using simulation and mixed practice to build
      competence.
AB  - The acquisition of competence in diagnostic reasoning is essential for medical
      trainees. Exposure to a variety of patient presentations helps develop the skills
      of diagnostic reasoning, but reliance on ad hoc clinical encounters is
      inefficient and does not guarantee timely exposure for all trainees. We present a
      novel teaching series led by emergency physicians that builds upon the existing
      medical education literature to teach diagnostic reasoning to preclinical (2nd
      year) medical students. The series used emergency department simulations
      involving patient actors and simulated vital signs to provide students with
      exposure to three acute care presentations: chest pain, abdominal pain, and
      headache. Emergency physicians coached and provided immediate feedback to the
      students as they actively worked through diagnostic reasoning. The participating
      medical students reported benefit from these sessions immediately following the
      sessions and in an 18-month follow-up survey where the students could consider
      the impact of the sessions on their clinical clerkship. Students felt that the
      sessions had assisted them in recognizing the key features of relevant diagnoses
      during clerkship as well as providing a helpful adjunct to their in-class
      learning.

PMID- 28743324
TI  - Atomic Force Microscopy Study of the Anti-inflammatory Effects of Triptolide on
      Rheumatoid Arthritis Fibroblast-like Synoviocytes.
AB  - High-resolution atomic force microscopy (AFM) was used for the in situ evaluation
      of the anti-inflammatory effects of triptolide on rheumatoid arthritis (RA)
      fibroblast-like synoviocytes (FLS) to understand the anti-RA effects of
      triptolide, based on the morphological and biophysical changes observed in RA
      FLS. RA-FLS have been reported to play a primary role in inflammatory bone
      destruction during the development of RA and thus are regarded as an important
      target for RA treatment. Triptolide pretreatment significantly inhibited tumor
      necrosis factor-alpha-induced expression of the interleukin (IL)-1beta, IL-6, and
      IL-8 genes in MH7A cells. Using AFM, we showed that triptolide-induced
      morphological damage in MH7A cells by inducing significant ultrastructure changes
      in the membrane, which were closely related to triptolide-induced apoptosis in
      MH7A cells. Using force measurements determined with AFM, triptolide was shown to
      increase the stiffness of MH7A cells. These findings not only revealed the strong
      anti-inflammatory effects of triptolide on RA-FLS, highlighting triptolide as a
      potential anti-RA agent, but also revealed the possible use of AFM for studying
      anti-inflammatory responses in RA-FLS, which we expect to be developed into a
      potential tool for anti-RA drug studies in RA-FLS.

PMID- 28743325
TI  - Low Doses of Simvastatin Potentiate the Effect of Sodium Alendronate in
      Inhibiting Bone Resorption and Restore Microstructural and Mechanical Bone
      Properties in Glucocorticoid-Induced Osteoporosis.
AB  - By using an experimental model of dexamethasone-induced osteoporosis we
      investigated the effects of different therapeutic schemes combining sodium
      alendronate (SA) and simvastatin on bone mineral and protein composition,
      microstructural and mechanical remodeling. Wistar rats were randomized into eight
      groups: G1: non-osteoporotic; G2: osteoporotic; G3, G4, and G5: osteoporotic+SA
      (0.2, 0.4, and 0.8 mg/kg, respectively); G6, G7, and G8: osteoporotic+SA (0.2,
      0.4, and 0.8 mg/kg, respectively)+simvastatin (0.4, 0.6, and 1 mg/kg,
      respectively). Osteoporosis was induced by dexamethasone (7 mg/kg, i.m.) once a
      week for 5 weeks. All treatments were administered for 8 weeks. Dexamethasone
      increased serum levels of alkaline phosphatase, calcium, phosphorus, and urea,
      especially in non-treated animals, which showed severe osteoporosis.
      Dexamethasone also induced bone microstructural fragility and reduced mechanical
      resistance, which were associated with a marked depletion in mineral mass,
      collagenous and non-collagenous protein levels in cortical and cancellous bone.
      Although SA has attenuated osteoporosis severity, the effectiveness of drug
      therapy was enhanced combining alendronate and simvastatin. The restoration in
      serum parameters, organic and inorganic bone mass, and mechanical behavior showed
      a dose-dependent effect that was potentially related to the complementary
      mechanisms by which each drug acts to induce bone anabolism, accelerating tissue
      repair.

PMID- 28743326
TI  - A Review of Surfactant Role in Soil Clogging Processes at Wastewater Exfiltration
      Locations in Sewers.
AB  - Wastewater contains significant sources of pollutants and contaminants. often
      the failure of a pipe, inadequate sealing or corrupt pipe-connections cause the
      loss of raw sewage, which percolates into the nearby soil. As a consequence, a
      colmation layer in conjunction with soil clogging is developing, which regulates
      the exfiltration rate. Recently, literature has emerged that offers findings
      about the effects of wastewater surfactants on the change of physical properties
      of the soil. A survey of published literature in this field provides information
      highlighting the influential mechanisms of surfactants in soil clogging through
      physical, chemical and biological processes. Therefore, to provide a
      comprehensive approach, this review describes the adsorption mechanisms of
      surfactants on organic and inorganic particles, at gas-bubbles and at biomass. We
      also provided our own input to the description of the adsorption of surfactants
      at fluid/fluid and fluid/solid interfaces in porous media associated with the
      clogging process.

PMID- 28743327
TI  - Predictions of Diffuse Pollution by the HSPF Model and the Back-Propagation
      Neural Network Model.
AB  - Watershed models are important tools for predicting the possible change of
      watershed responses. Environmental models comprise the deterministic model and
      the probabilistic model. This study discusses the Hydrological Simulation Program
      Fortran (HSPF) and the Back-Propagation Neural Network (BPNN); these two models
      represent the deterministic model and the probabilistic model, respectively. As
      the properties of the two models are distinct, they have differing abilities to
      predict surface-runoff pollution. For the two models, the runoff simulation
      results are satisfactory. However, due to the limitation of the water quality
      monitoring records, pollution simulation is more difficult than runoff
      simulation. The results indicate that the prediction accuracy in the pollution
      simulation can be improved by adjusting the BPNN neurons. On the contrary,
      improving the prediction accuracy is limited by HSPF. Although the flexibility of
      BPNN is higher than HSPF, sufficient historical monitoring records are important
      for both of these models.

PMID- 28743328
TI  - Performance Evaluation of Membrane-Based Septic Tank and Its Reuse Potential for
      Irrigating Crops.
AB  - Membrane technology, being the most emerging wastewater treatment option, has
      gained substantial importance with the massive objective of the reuse potential
      of wastewater. Keeping this in view, the present study was conducted with the
      rationale to evaluate the performance efficiency of membrane-based septic tank
      (MBST), and its reuse perspective for irrigating crops. The septic tank was
      designed by submerging a woven fiber microfiltration membrane module to treat
      domestic wastewater. Three crops Triticum aestivum (wheat), Coriandrum sativum
      (coriander), and Mentha arvensis (mint) were selected to be irrigated with
      treated MBST effluent, untreated wastewater, and tap water (as a control) for
      comparative growth analysis. Two pathogenic strains, Escherichia coli and
      Salmonella sp. were selected as reference microbes and their translocation rate
      was observed in root, shoot, and leaves. Upon maturity, the roots, shoots, and
      leaves of the above-mentioned plants were aseptically removed for microbiological
      analysis. Strains were analyzed, using analytical profile index and PCR analysis.
      Maximum removal efficiencies for MBST in terms of chemical oxygen demand (COD),
      turbidity, nutrients deduction (phosphorus), and indicator bacteria (Escherichia
      coli) were found to be 73, 96, 48, and 88%, respectively. Significant bacterial
      load reduction (p < 0.001) in terms of E. coli (3.8 log CFU/100 mL) and helminths
      (2 eggs/L) was observed in treated water. High plant yield was observed when
      irrigated with treated water as compared to tap water, as minimal nutrient
      removal (48%) was recorded in treated water, with the germination percentage of
      88.8%.

PMID- 28743329
TI  - Effects of Flow Fluctuation on Dilution and Spreading in a Self-Affine Fracture.
AB  - In this work, the spreading and dilution (mixing) processes of the miscible
      compound were analyzed numerically by three-dimensional Lattice Boltzmann Method
      (LBM) at a pore scale in a non-uniform flow field. The authors proposed an
      aperture-related dilution index to quantify the local dilution process in the
      different aperture regions. The results showed that the fluctuation of the
      compound spreading caused by the flow fluctuation depended on both the aqueous
      diffusivity and the frequency of the flow fluctuation. The flow fluctuation
      increased remarkably the original dilution index when the aqueous diffusivity of
      the miscible compound was relatively low. However, the analysis of the aperture
      related dilution index showed that the degree of the dilution in smaller aperture
      regions was less than that in larger aperture regions, indicating that there was
      more incomplete dilution (mixing) in the smaller aperture region.

PMID- 28743330
TI  - Sludge Reduction in the Activated Sludge Process Strengthened by Enhanced
      Ozonation Oxidation.
AB  - A novel radial-axial mixer and microbubble ozone reactor for enhancing sludge
      disintegration was designed. In the batch studies, the new reactor was shown to
      be significantly effective in improving sludge disintegration and increasing
      ozone utilization. For ozone dosages of 0.02 to 0.3 gO3/gTSS (total suspended
      solids) at pH = 10, the average sludge disintegration ratio was more than 17 +/-
      0.83% higher than that of the conventional reactor. An activated sludge process
      coupled with discharged sludge ozonated was run for 60 days to evaluate the
      influence of ozonated sludge feeding on the sludge yield coefficient and effluent
      quality. Although the effluent chemical oxygen demand (COD) and suspended solids
      (SS) increased slightly, these values were well below the discharge limit.
      Furthermore, a sludge reduction efficiency of 95% was attained. The experimental
      results indicated that the combination of sludge ozonation with the activated
      sludge process could generate a high quality of effluent and a small sludge
      yield.

PMID- 28743331
TI  - [Chinese emergency medicine expert consensus on diagnosis and treatment of sepsis
      complicated with disseminated intravascular coagulation].

PMID- 28743332
TI  - [Clinical significance of early immunological paralysis in patients with severe
      H1N1 influenza A].
AB  - OBJECTIVE: To analysis the immunological characteristics of patients with severe
      H1N1 influenza A, and to provide theoretical basis for predicting the prognosis
      of the disease. METHODS: A retrospective analysis was conducted. The clinical
      data of 15 patients diagnosed with severe H1N1 influenza A and admitted to
      Shanghai General Hospital of Nanjing Medical University from October 2015 to
      December 2016 were collected. All the patients were divided into survival and
      death groups according to 28-day survival. Clinical characteristics, treatment
      algorithm, organ function, inflammatory reaction and immune cell status were
      compared, and Cox regression was used to decide the risk factors of 28-day death
      in patients with severe H1N1 infection A. RESULTS: All 15 patients with severe
      H1N1 infection A were enrolled, most of who presented with cough (93.3%), fever
      (86.7%), sputum production (80.0%), shortness of breath (73.3%), myalgia (40.0%)
      and fatigue (40.0%). All had been received anti-virus, antibiotics, mechanical
      ventilation and anti-coagulation therapy; some were treated with prone position,
      neuromuscular blocker and extracorporeal membrane oxygenation (ECMO). The
      incidences of acute myocardial and kidney injury were high, and the acute
      physiology and chronic health evaluation II (APACHE II) score (14.1+/-6.1) and
      sequential organ failure assessment (SOFA) score (9.6+/-4.1) implicated the
      critical condition. Of 15 patients, 4 patients died in 28 days, while 11 were
      cured and discharged. Compared with survival group, the patients in death group
      had higher levels of APACHE II score (22.7+/-3.8 vs. 11.8+/-3.8), troponin [cTn
      (MUg/L): 0.52 (0.07, 2.02) vs. 0.15 (0.10, 0.45)] and blood urea nitrogen [BUN
      (mmol/L): 11.9 (6.7, 29.1) vs. 3.9 (2.7, 6.8)] and a lower level of blood
      platelets count [PLT (*109/L): 76+/-33 vs. 146+/-49, all P < 0.05]. The levels of
      C-reactive protein (CRP) and interleukin-6 (IL-6) within 24 hours of admission in
      death group were significantly higher than those of survival group [CRP (mg/L):
      172.2+/-88.5 vs. 74.8+/-33.1, IL-6 (ng/L): 283.3 (140.1, 711.0) vs. 18.5 (12.7,
      71.4), both P < 0.01]. Compared with survival group, the expressions of CD3+,
      CD4+, CD8+ T cells and natural killer cell (NK cell) in death group were
      significantly decreased (CD3+ T cell: 0.348+/-0.119 vs. 0.573+/-0.106, CD4+ T
      cell: 0.135+/-0.046 vs. 0.344+/-0.098, CD8+ T cell: 0.089+/-0.057 vs. 0.208+/
      0.054, NK cell: 0.124+/-0.057 vs. 0.252+/-0.182, all P < 0.05), but there were no
      significant differences in CD4+/CD8+ ratio and human leucocyte antigen-DR
      positive (HLA-DR+) T cell between death group and survival group (CD4+/CD8+
      ratio: 1.57+/-0.26 vs. 1.83+/-0.54, HLA-DR+ T cell: 0.035+/-0.022 vs. 0.062+/
      0.036, both P > 0.05). B lymphocyte in death group was significantly higher than
      that of survival group (0.477+/-0.136 vs. 0.229+/-0.121, P < 0.01). Cox
      regression analysis revealed that APACHE II score [risk ratio (RR) = 20.4, 95%
      confidence interval (95%CI) = 5.3-31.2, P = 0.017], CD4+ T cell (RR = 11.1, 95%CI
      = 5.1-20.0, P = 0.048) and CD8+ T cell (RR = 9.1, 95%CI = 4.3-16.7, P = 0.049)
      were independently risk factors of 28-day survival of patients with severe H1N1
      influenza A. CONCLUSIONS: Immunological paralysis and severe inflammatory
      response were early complicated with severe H1N1 influenza A, and these were
      significantly associated with prognosis.

PMID- 28743333
TI  - [Comprehensive effect of subglottic secretion drainage on patients with
      mechanical ventilation in ICU: a Meta-analysis].
AB  - OBJECTIVE: To systematically evaluate the comprehensive effect of subglottic
      secretion drainage (SSD) on patients with mechanical ventilation (MV) in
      intensive care unit (ICU). METHODS: The randomized controlled clinical trials
      (RCTs) comparing SSD (intervention group) versus non-SSD (control group) in adult
      patients with MV in ICU was collected through the databases such as the PubMed
      database of the National Library of Medicine, CNKI, Wanfang database and the
      Chinese journal of science and technology database (VIP). The subjects were ICU
      patients with MV, and the retrieval time ranged from January 2006 to December
      2016. Two reviewers independently screened the studies according to the inclusive
      and exclusive criteria, extracted the data, and assessed the quality. Then RevMan
      5.3 software was used for Meta-analysis. Sensitivity analysis was performed using
      Stata 11.0 software. Funnel plot was used to analyze publication bias. RESULTS:
      In the 1 004 documents obtained from preliminary screening, a total of 13 studies
      involving 2 052 patients were enrolled after excluding duplicated documents and
      literature did not meet the inclusion criteria, with 1 021 patients in
      intervention group, and 1 031 in control group. Meta-analysis showed that
      compared with control group, the application of SSD in patients with MV could
      contribute to the reduction of the incidence of ventilator-associated pneumonia
      [VAP; risk ratio (RR) = 0.54, 95% confidence interval (95%CI) = 0.46-0.64, P <
      0.000 01], the duration of MV [mean difference (MD) = -3.29, 95%CI = -4.53 to 
      2.05, P < 0.000 01] and length of hospital stay (MD = -4.27, 95%CI = -7.36 to 
      1.18, P = 0.007) were shortened, while there was no significant difference in ICU
      or hospital mortality rate between the intervention group and control group (RR =
      0.89, 95%CI = 0.73-1.09, P = 0.25). The sensitivity analysis for studies enrolled
      in Meta-analysis of MV duration showed that individual research results were
      stable through step remove of the included literatures and combined calculation
      of the remaining literature value, suggesting that individual research results
      were stable, and would not have a significant impact on the overall results. The
      results of the funnel analysis showed that there was a symmetry in the inclusion
      studies, and no significant publication bias was found. CONCLUSIONS: SSD did have
      effect in reducing the incidence of VAP, shortening the duration of MV and length
      of hospital stay, while there was no significant effect on reducing mortality
      rate. Effective use of SSD is an important measure to prevent VAP. It is
      necessary to objectively evaluate the clinical effect of SSD.

PMID- 28743334
TI  - [Expressions of microRNA-127-5p in bronchoalveolar lavage fluid of patients with
      severe pneumonia and its diagnostic value].
AB  - OBJECTIVE: To observe differential expressions of microRNA-127-5p (miR-127-5p) in
      bronchoalveolar lavage fluid (BALF) of patients with severe pneumonia and the
      value of miR-127-5p in the diagnosis of severe pneumonia. METHODS: Thirty severe
      pneumonia patients and 10 non-respiratory infection patients who needed
      mechanical ventilation after surgery admitted to Department of Critical Care
      Medicine of General Hospital of Ningxia Medical University from January to
      December in 2015 were enrolled, whose specimens of BALF were collected. The
      differential expressions of miRNA in BALF of patients in both groups were
      screened by miRNA chip technique to preliminarily establish miRNA differential
      expression profiles in BALF of severe pneumonia, and the miRNAs which were up
      regulated and down-regulated were screened out. The expression levels of miR-127
      5p were determined using a real-time fluorescent quantitative polymerase chain
      reaction (PCR). The value of miR-127-5p expression in the diagnosis of severe
      pneumonia was evaluated with receiver-operating characteristic curve (ROC).
      RESULTS: All of the 40 patients were enrolled in the final analysis. Differential
      expression spectrum of miRNA in severe pneumonia patients was initially built, in
      which 40 miRNAs were up-regulated and 113 miRNAs were down-regulated. Compared
      with non-respiratory infection patients, the expressions of miR-127-5p were
      significantly lowered in severe pneumonia patients (2-Delta DeltaCT: 0.578+/
      0.226 vs. 1.004+/-0.337) with statistical difference (t = 4.552, P = 0.000). ROC
      curve analysis showed that the area under ROC curve (AUC) of miR-127-5p for
      diagnosis of severe pneumonia was 0.855 [95% confidence interval (95%CI) = 0.721
      0.989, P = 0.001], with the optimal sensitivity and specificity of 86.7% and
      70.0% respectively with 0.840 as the critical value, and the positive likelihood
      ratio was 2.89, the negative likelihood ratio was 0.19. CONCLUSIONS: miR-127-5p
      in BALF could be used as a new biomarker for the diagnosis of severe pneumonia.

PMID- 28743335
TI  - [Regulation of paxillin tyrosine phosphorylation via inhibition of c-Abl kinase
      to protect ventilator induce lung injury in vivo in rats].
AB  - OBJECTIVE: To determine whether the inhibition of paxillin tyrosine residues 31
      and tyrosine residues 118 (Pxn Y31 and Pxn Y118) phosphorylation via inhibition
      of c-Abl kinase will effectively block its downstream effector molecules vessel
      endothelium-cadherin (VE-cad), and whether Rho/Rho kinase activation which will
      induce the vascular barrier dysfunction. METHODS: Ninety healthy male Sprague
      Dawley (SD) rats were randomly divided into nine groups (each n =10). Only
      tracheotomy was undergone in the sham group. Groups of protective ventilation
      were set at a volume tidal (VT) of 6 mL/kg, a positive end-expiratory pressure
      (PEEP) of 5 cmH2O (1 cmH2O = 0.098 kPa) for 1 hour or 2 hours (namely group PVT 1
      h and group PVT 2 h), respectively. Groups of high VT were put on mechanical
      ventilation (MV) at high VT 30 mL/kg, PEEP 0 for 1 hour or 2 hours (namely group
      HVT 1 h and group HVT 2 h), respectively. Groups UO126 and AG957 pretreatment
      were set on MV at HVT for 1 hour or 2 hour respectively, but they were given
      p42/44 mitogen-activated protein kinase (p42/44MAPK) inhibitor UO126 1 mg/kg by
      intraperitoneal injection or c-Abl kinase inhibitor AG957 10 mL/kg by
      intragastric injection 1 hour before HVT ventilation. All the animals were
      sacrificed after experiments and specimens of lung tissues and bronchoalveolar
      lavage fluid (BALF) were harvested. Pulmonary vascular permeability was measured
      by Evans blue (EB). The levels of tumor necrosis factor-alpha (TNF-alpha) in BALF
      were measured by enzyme linked immunosorbent assay (ELISA). Then the change of
      lung tissue pathology was observed with light microscope, diffuse alveolar damage
      system (DAD) score and lung wet/dry ratio (W/D) were estimated. The
      myeloperoxidase (MPO) activity was measured by colorimetric analysis,
      phosphorylations of c-Abl Y245, Pxn Y31, Pxn Y118, VE-cad Y658, p42/44MAPK
      Y202/Y204, myosin light chain (MLC) and myosin-associated phosphatasetype Y696
      (MYPT Y696) were determined by Western Blot. RESULTS: (1)There were no obvious
      pathological changes in the lung tissue in the sham group and PVT 1 h or 2 h
      group, and also there were no significant differences in all the parameters
      between above groups. However, the injury in lung tissue was severe in the HVT
      groups. In addition, DAD score, lung W/D ratio, EB content, the activity of MPO,
      and TNF-alpha in BALF in HVT groups were significantly higher than those in sham
      group and PVT groups. After pretreatment with AG957 or UO126, all the parameters
      were significantly decreased as compared with those of groups HVT. (2) The levels
      of phosphorylation of the proteins in lung tissue in HVT groups were increased as
      compared with those of group sham and groups PVT, especially at 2 hours of MV.
      However, compared with groups HVT, the level of p-VE-cad Y658 in lung tissue
      decreased significantly in group AG957 and group UO126 at 2 hours after HVT.
      However, the levels of all phosphorylated proteins at 2 hours were significantly
      lowered in the AG957 group compared with those of the HVT group [p-c-Abl Y245
      (gray value): 0.29+/-0.04 vs. 0.42+/-0.04, p-Pxn Y31 (gray value): 0.51+/-0.03
      vs. 0.70+/-0.05, p-Pxn Y118 (gray value): 0.65+/-0.04 vs. 0.91+/-0.04, p-VE-cad
      Y658 (gray value): 0.77+/-0.07 vs. 1.32+/-0.07, p-p42/44MAPK Y202/Y204 (gray
      value): 0.38+/-0.06 vs. 0.61+/-0.03, p-MLC (gray value): 0.37+/-0.04 vs. 0.77+/
      0.05, p-MYPT Y696 (gray value): 0.54+/-0.05 vs. 0.87+/-0.06, all P < 0.05]. After
      pretreatment with UO126, the phosphorylation level of VE-cad in lung tissue at 2
      hours was significantly lower than that of HVT group (gray value: 0.74+/-0.04 vs.
      1.32+/-0.07), and the phosphorylation levels of p42/44MAPK and its downstream
      effector molecules MLC and MYPT Y696 were also significantly decreased [p
      p42/44MAPK Y202/Y204 (gray value): 0.38+/-0.07 vs. 0.61+/-0.03, p-MLC (gray
      value): 0.37+/-0.04 vs. 0.77+/-0.05, p-MYPT Y696 (gray value): 0.55+/-0.05 vs.
      0.87+/-0.06, all P < 0.05]. CONCLUSIONS: Pxn Y31 and Pxn Y118 phosphorylation
      could be blocked by inhibition of c-Abl kinase, which could strengthen VE-cad at
      attachment junction and might block formation of Pxn-guanine nucleotide-exchange
      factor H1 (GEF-H1)-p44/42MAPK signalosome which induce activation local Rho
      signaling, lead to activation of MLC phosphorylation, actomyosin contraction, and
      increase endothelial permeability.

PMID- 28743336
TI  - [Analysis of factors affecting the prognosis of ICU patients by multiple logistic
      regression model: a retrospective cohort study of 1 299 patients in 12
      consecutive years].
AB  - OBJECTIVE: To explore the prognostic factors of intensive care unit (ICU)
      patients. METHODS: A retrospective cohort study was conducted. The clinical data
      of patients admitted to ICU of Beijing Geriatric Hospital from January 2005 to
      December 2016 were collected. According to the prognosis, the patients were
      divided into death group and survival group, and the mortality trend with time
      and age was observed. Survival and death were treated as dependent variables,
      while the gender, age, reason of ICU admission, acute physiology and chronic
      health evaluation II (APACHE II) score, whether undergoing invasive mechanical
      ventilation (MV), invasive MV reason, duration of invasive MV, whether successful
      weaning, whether ICU nosocomial infection, hospital acquired pneumonia (HAP),
      central line-associated bloodstream infection (CLABSI), acute kidney injury (AKI)
      occurred, whether undergoing continuous blood purification (CBP), whether septic
      shock occurred, whether undergoing invasive hemodynamic monitoring or blood
      transfusion and length of ICU stay were used as the independent variables. First,
      the clinical data was analyzed by univariate analysis. Second, the independent
      variables influencing the dependent variable were analyzed by logistic regression
      analysis to screen out prognostic factors of ICU patients. RESULTS: During the
      study period, 1 325 patients were treated, 26 patients with missing data, 1 299
      patients in final group, 865 patients in survival group, and 434 in death group.
      The proportion of men in the patients was larger (67.7%), and the age span was
      larger (16-105 years old). The mortality rate in different years showed no
      significant difference (chi 2 = 16.712, P = 0.117), and with the increase of age,
      the mortality rate of ICU showed an upward trend (chi 2 = 16.399, P = 0.022). The
      univariate analysis showed that ICU deaths were unrelated to gender, but
      associated with age, APACHE II score, invasive MV, invasive MV reason, duration
      of invasive MV, successful weaning, ICU nosocomial infection, HAP, CLABSI, AKI,
      septic shock, whether CBP or invasive hemodynamic monitoring, blood transfusion,
      the reason of ICU admission and the length of ICU stay (all P < 0.05). The
      relevant factors with statistical difference found in univariate analysis were
      analyzed in logistic regression analysis, which showed that whether successful
      weaning [odds ratio (OR) = 0.016, 95% confidence interval (95%CI) = 0.010-0.025],
      and whether AKI (OR = 3.917, 95%CI = 2.331-6.582) or septic shock occurred (OR =
      2.808, 95%CI = 1.604-4.915) were the dependent variables of death or survival
      (all P = 0.000). Regression coefficient (beta value) of successful weaning was 
      4.155, suggesting that unsuccessful weaning patients were likely to die. The beta
      value of AKI and septic shock was 1.365 and 1.033, suggesting that the patients
      with AKI or septic shock were more likely to die. CONCLUSIONS: Whether the
      success of weaning, whether the occurrence of AKI or septic shock are independent
      prognostic factors for the prognosis of ICU patients. Measures for the prevention
      of the above three aspects could improve the prognosis of ICU patients.

PMID- 28743337
TI  - [Effect of multidrug resistant associated protein 4 overexpression on
      lipopolysaccharide-induced vascular endothelial hyperpermeability and its
      mechanism].
AB  - OBJECTIVE: To investigate the effect of multidrug resistance protein 4 (MRP4)
      overexpression on lipopolysaccharide (LPS)-induced vascular endothelial
      hyperpermeability of rat pulmonary micro-vascular endothelial cells (PMVECs) and
      its molecule mechanism. METHODS: Three to six passages of PMVECs were cultured in
      vitro, and they were divided into three groups: the cells in LPS group were only
      challenged by LPS 10 MUg/mL after being cultured in serum-free medium for 24
      hours; the cells in Ad-shRNA and Ad-MRP4 groups were infected with the empty
      virus control or recombinant adenovirus expressing MRP4 for 2 hours, and then
      were cultured in serum-free medium for 24 hours followed by stimulation of LPS 10
      MUg/mL. Endothelial permeability was assayed by the Transwell chamber models at
      2, 6, 12, and 24 hours after LPS stimulation. Intracellular cyclic adenosine
      monophosphate (cAMP) levels were detected by enzyme-linked immunosorbent assay
      (ELISA). The morphological characteristics and distribution of F-actin was
      determined by laser confocal fluorescence microscope. The protein expressions of
      MRP4, beta-catenin, vascular endothelium-cadherin (VE-cad) and ZO-1 were measured
      by Western Blot. RESULTS: (1) After LPS stimulation, endothelium permeability and
      intracellular cAMP levels in PMVECs were significantly increased, peaked at 12
      hours, and then decreased after 24 hours. Compared with LPS group and Ad-shRNA
      group, PMVECs of Ad-MRP4 group were exhibited a significant increase in
      endothelial permeability [12-hour permeability (A value): 1.88+/-0.06 vs. 1.12+/
      0.17, 1.10+/-0.18] and a significant decrease in intracellular cAMP level [12
      hour cAMP (MUg/L): 2.39+/-0.02 vs. 2.97+/-0.01, 3.00+/-0.02, all P < 0.05]. There
      was no significant difference in endothelium permeability and intracellular cAMP
      levels at all time points between the LPS group and the Ad-shRNA group (all P >
      0.05). (2) Under laser confocal fluorescence microscope, after LPS stimulation,
      the stress fiber formation was induced in three groups. But there were pronounced
      irregular aggregation of fiber in PMVECs of Ad-MRP4 group. (3) Furthermore,
      compared with LPS group and Ad-shRNA group, protein expression of MRP4 in Ad-MRP4
      group was dramatically increased (gray value: 0.76+/-0.03 vs. 0.44+/-0.02, 0.43+/
      0.02, both P < 0.05), and the protein expressions of beta-catenin, VE-cad, and ZO
      1 were significantly decreased [beta-catenin (gray value): 0.14+/-0.03 vs. 0.23+/
      0.04, 0.23+/-0.03); VE-cad (gray value): 0.21+/-0.01 vs. 0.34+/-0.02, 0.35+/
      0.04; ZO-1 (gray value): 0.14+/-0.02 vs. 0.37+/-0.06, 0.33+/-0.07, all P < 0.05].
      There was no significant difference in all protein expressions between the LPS
      group and Ad-shRNA group (all P > 0.05). CONCLUSIONS: MRP4 overexpression can
      decrease intracellular cAMP levels, reduce intercellular junction protein
      expression, and then exaggerate LPS-induced vascular endothelial
      hyperpermeability.

PMID- 28743338
TI  - [Clinical characteristics and prognosis in patients with high plasma level of
      procalcitonin: an analysis in 188 patients].
AB  - OBJECTIVE: To investigate the clinical characteristics and prognosis of patients
      with high level of plasma procalcitonin (PCT > 100 MUg/L), and to improve the
      clinician's understanding, diagnosis and treatment of this kind of patients.
      METHODS: A retrospective study was conducted. The clinical data of patients with
      plasma PCT over 100 MUg/L within 48 hours of admission admitted to Second
      Affiliated Hospital of Zhejiang University School of Medicine from February 2013
      to December 2016 were collected, and the clinical characteristics were analyzed.
      The patients were divided into survival and death groups according to 28-day
      prognosis. The general data and laboratory parameters including vital signs, 24
      hour urine output, routine blood test, blood biochemical tests, coagulation
      parameters, myocardial enzymes and arterial blood gas analysis were collected.
      The risk factors of mortality were analyzed using multi-logistic regression
      analysis. RESULTS: 188 patients with high level of plasma PCT were enrolled.
      There were 128 male patients (68.1%) with the average age of 62 (49, 75) years.
      Most patients were admitted in intensive care unit (ICU, 70.7%, 133/188). Major
      diagnosis was sepsis (91.0%), followed by multiple organ dysfunction syndrome
      (MODS, 57.4%), post large operation of thorax and abdomen (20.7%), trauma/burns
      (13.8%) and post-cardiopulmonary resuscitation (CPR, 6.4%). Of all the 188
      patients, 115 patients survived and 73 died with a mortality of 38.8%. The
      parameters in the death group, including the percentages of MODS (84.9% vs.
      40.0%), trauma/burns (26.0% vs. 6.1%), post-CPR (13.7% vs. 1.7%), ventilator
      support (82.2% vs. 40.9%) and shock (100.0% vs. 60.0%), the numbers of principal
      diagnosis [2.0 (2.0, 3.0) vs. 2.0 (1.0, 2.0)], acute physiology and chronic
      health evaluation II score [APACHE II score: 24 (19, 28) vs. 14 (10, 16)] and
      sequential organ failure assessment (SOFA) score [16.0 (12.5, 18.0) vs. 9.0 (6.0,
      12.0)], as well as liver function, coagulation parameters, myocardial enzymes and
      lactic acid (Lac) levels were significantly higher than those in the survival
      group, but the platelet (PLT) count in the death group was significantly lower
      than that in the survival group [*109/L: 62.00 (21.50, 111.00) vs. 93.00 (53.00,
      136.00), all P < 0.05]. The parameters with statistical significance in the
      univariate analysis were enrolled in the multiple factor logistic regression
      analysis, which showed that patient with a high score of APACHE II [odds ratio
      (OR) = 1.290, 95% confidence interval (95%CI) = 1.121-1.484, P = 0.000] or the
      occurrence of MODS (OR = 7.264, 95%CI = 1.762-29.941, P = 0.006) at admission had
      a poor prognosis. CONCLUSIONS: The primary patients with high levels of plasma
      PCT (> 100 MUg/L) were diagnosed with sepsis, MODS, trauma and post-CPR,
      complicated with respiratory and circulatory insufficiency. These factors of
      trauma, MODS and cardiac arrest, and some laboratory parameters including PLT,
      Lac, liver function, coagulation spectrum, and cardiac enzymes were correlated
      with the prognosis of the patients with high levels of plasma PCT. High APACHE II
      score and the incidence of MODS might be independent predictors of poor prognosis
      in the patients with high levels of plasma PCT.

PMID- 28743339
TI  - [Predictive value of ultrasonic diaphragm thickening fraction on successful
      weaning for patients with myasthenia gravis crisis].
AB  - OBJECTIVE: To confirm the predictive value of diaphragm thickening fraction (DTF)
      on successful weaning by bedside ultrasound in patients with myasthenia gravis
      crisis. METHODS: A prospective study was conducted. The patients with myasthenia
      gravis crisis undergoing mechanical ventilation admitted to Department of
      Critical Care Medicine of the Affiliated Hospital of Qingdao University from
      March 2015 to February 2017 were enrolled. All patients underwent a low level
      pressure support mode of spontaneous breathing test (SBT), and rapid shallow
      breathing index (RSBI) was recorded. The indicators of right diaphragm thickness
      at the end of inspiration (DTei) and expiration (DTee) were determined by bedside
      ultrasound at 5 minutes and 60 minutes of SBT, and DTF was calculated, the
      changes in above parameters were observed during SBT. The patients were divided
      into successful weaning group and failure weaning group, and the differences in
      above indexes were compared between the two groups. Receiver operating
      characteristic curve (ROC) was used to evaluate the predictive value of DTF and
      RSBI at 60 minutes of SBT on successful weaning. RESULTS: A total of 37 patients
      were enrolled in the study. Ultrasonic measurement data of 63 person-times at 5
      minutes of SBT and 50 at 60 minutes of SBT were obtained. There were no
      statistical differences in RSBI, DTei, DTee, and DTF at 5 minutes of SBT between
      successful weaning group (n = 33) and failure weaning group (n = 30). At 60
      minutes of SBT, compared with successful weaning group (n = 33), the patients in
      failure weaning group (n = 17) had a higher RSBI (times*min-1*L-1: 80.41+/-29.08
      vs. 63.94+/-23.84, t = 2.146, P = 0.037), and lower DTee, DTei and DTF [DTee
      (mm): 22.00+/-6.25 vs. 25.45+/-4.99, t = 2.127, P = 0.039; DTei (mm): 27.94+/
      6.19 vs. 38.48+/-6.15, t = 5.731, P = 0.000; DTF: (24.46+/-14.11)% vs. (62.04+/
      30.21)%, t = 4.845, P = 0.000]. There were no statistical differences in RSBI,
      DTei, DTee, and DTF between 5 minutes and 60 minutes of SBT in 33 person-time
      successful weaning (all P > 0.05). In 17 person who had 60 minutes of SBT but
      failed weaning, the RSBI at 60 minutes of SBT was significantly higher than that
      at 5 minutes (times*min-1*L-1: 80.41+/-29.08 vs. 57.29+/-22.46, t = 2.400, P =
      0.029), and DTei and DTF were significantly decreased [DTei (mm): 27.94+/-6.19
      vs. 35.35+/-6.84, t = 3.024, P = 0.000; DTF: (24.46+/-14.11)% vs. (61.89+/
      23.97)%, t = 5.810, P = 0.000], but the change of DTee during SBT showed no
      statistical significance. ROC curve analysis showed that the area under ROC curve
      (AUC) of DTF at 60 minutes of SBT for predicting successful weaning was 0.898;
      when DTF >= 27.9% as the cut-off point, the sensitivity was 93.9%, specificity
      was 70.6%. The AUC of RSBI for predicting successful weaning was 0.669; when RSBI
      >= 86.50 times*min-1*L-1 as the cut-off point, the sensitivity was 81.8%,
      specificity was 52.9%. CONCLUSIONS: DTF at 60 minutes of SBT is the effective
      index of successful weaning prediction in mechanical ventilation patients with
      myasthenia gravis crisis.

PMID- 28743340
TI  - [Ventilator bundle guided by context of JCI settings can effectively reduce the
      morbidity of ventilator-associated pneumonia].
AB  - OBJECTIVE: To observe the impact of improving the compliance of ventilator bundle
      on morbidity of ventilator-associated pneumonia (VAP) in intensive care unit
      (ICU) patients undergoing mechanical ventilation (MV) guided by context of Joint
      Commission International (JCI) settings, and to study the oral care efficacy of
      suction tube sponge brush. METHODS: A prospective study was conducted. The
      patients who needed MV admitted to Department of Critical Care Medicine of the
      First Affiliated Hospital of Xiamen University from January 2013 to December 2016
      were enrolled. In the context of JCI settings, necessary measurements were taken
      to enhance the compliance of ventilator bundle each year. In 2013, the preventive
      measures were set up and the education was strengthened. In 2014, the compliance
      of hand hygiene and bedside elevation was strengthened. In 2015, a control study
      was conducted to evaluate the effect between the traditional cotton dipped in
      chlorhexidine and the suction tube sponge brush rinsed with chlorhexidine on oral
      health impact parameters. The suction tube sponge brush rinsed with chlorhexidine
      oral care was introduced to improve compliance. In 2016, electronic bundle
      checklist for daily self-audits was conducted. The annually morbidity of VAP
      through the software of hospital and ICU was collected and calculated. The annual
      incidence of VAP was indicated by the VAP cases per 1 000 MV days. Based on the
      VAP incidence rate in 2013 as 1, the VAP incidence-rate ratio (IRR) of each year
      was calculated. RESULTS: During the study period, a total of 2 733 patients
      admitted to the ICU, including 1 403 patients undergoing MV. Ninety-four of the 1
      403 patients with community-acquired pneumonia (CAP), aspiration pneumonia, back
      elevation ban, incomplete information, and withdrew from the study were excluded.
      1 399 patients undergoing MV were enrolled in the final analysis, with total MV
      days of 11 012 days, and 94 patients occurred VAP. The annual incidence of VAP
      was progressively declined from 2013 to 2016, and the VAP cases per 1 000 MV days
      were 17.0, 10.0, 5.9, 3.5 cases, respectively. Based on the VAP incidence rate in
      2013, the IRR of VAP from 2014 to 2016 was also progressively declined, which was
      0.59 [95% confidence interval (95%CI) = 0.35-0.98], 0.35 (95%CI = 0.18-0.64), and
      0.21 (95%CI = 0.09-0.41), with statistical significance (all P < 0.05). In 2013,
      ICU patients had the lowest rates of bedside elevation and hand hygiene
      compliance, which were 28.57% and 54.29%, respectively. Compared with 2013, by
      the implementation of two quality control circle (QCC) projects for bedside
      elevation and hand hygiene, the rates of bedside elevation and hand hygiene
      compliance were improved significantly in 2014, which were 82.35%, 91.18%,
      respectively (both P < 0.05). In 2015, the compliance of chlorhexidine oral care
      which was the worst performed in 2014 had been improved by the method of QCC, and
      the rate of the compliance was significantly higher than that in 2013 (87.10% vs.
      62.86%, P < 0.05). Compared with 2013, bundle compliance was significantly
      increased in 2016, except for the sterile operation of the suction tube [daily
      wake and weaning: 95.00% vs. 71.43%, bedside elevation for over 30degree angle:
      92.50% vs. 28.57%, hand hygiene: 97.50% vs. 54.29%, chlorhexidine mouth care once
      per 6-8 hours: 95.00% vs. 62.86%, turned back and posture drainage: 97.50% vs.
      80.00%], the differences were statistically significant (all P < 0.05). The
      incidences of bad breath, dirt residue and plaque were significantly lower in the
      group of oral care by using suction tube sponge brush with chlorhexidine (30
      cases) compared with the group of traditional cotton pad with chlorhexidine (30
      cases; bad breath: 10.0% vs. 40.0% %, dirt residue: 16.7% vs. 70.0%, plaque: 3.3%
      vs. 30.0%, all P < 0.05). There was no significant difference in the incidence of
      oral ulcers between the oral brush group and the traditional group (10.0% vs.
      30.0%, P > 0.05). CONCLUSIONS: Ventilator bundle can effectively reduce the
      morbidity of VAP in the context of JCI settings, and the oral care by using
      suction tube sponge brush and chlorhexidine can effectively improve oral hygiene.

PMID- 28743341
TI  - [Effect of external abdominal aorta compression on circulation during anesthesia
      induction in elderly patients].
AB  - OBJECTIVE: To investigate the effect of external abdominal aorta compression on
      circulation during anesthetic induction in elderly patients. METHODS: A
      prospective randomized controlled trial was conducted. Patients with age of 60-75
      years old, requiring a general anesthesia for non-abdominal surgery, and with II
      III class of American Society of Anesthesiologists (ASA) physical status
      classification, and admitted to General Hospital of Chinese People's Armed Police
      Forces from January to April in 2017 were enrolled. They were divided into
      abdominal aorta pressure group and control group according to random number
      method, with 20 patients in each group. In both groups, anesthesia was induced
      with midazolam, propofol, fentanyl and cisatracurium, and was maintained with
      propofol, remifentanil and cisatracurium. After successful intubation, the
      anesthesia machine was changed into mechanical ventilation. The patients in
      abdominal aorta pressure group were given abdominal aorta pressure 1 minute after
      induction of general anesthesia with midazolam till 5 minutes after intubation.
      The mean arterial pressure (MAP), heart rate (HR) and blood oxygen saturation
      (SpO2) were observed before anesthesia induction, immediately after anesthesia
      induction, immediately after intubation, 5 minutes and 10 minutes after
      intubation, respectively. The incidence of hypotension or bradycardia, and usage
      of ephedrine or atropine were recorded. RESULTS: There were no significant
      differences in MAP [mmHg (1 mmHg = 0.133 kPa): 83.6+/-4.7 vs. 82.9+/-4.7], HR
      (bpm: 67.3+/-5.9 vs. 65.9+/-5.7) and SpO2 (0.962+/-0.007 vs. 0.960+/-0.009)
      before anesthesia induction between abdominal aorta pressure group and control
      group (all P > 0.05). Immediately after anesthesia induction, the MAP and HR in
      control group were significantly decreased as compared with those before
      anesthesia induction [MAP (mmHg): 70.0+/-8.7 vs. 82.9+/-4.7, HR (bpm): 60.7+/-6.7
      vs. 65.9+/-5.7, both P < 0.05], and they were also significantly lower than those
      of abdominal aorta pressure group [MAP (mmHg): 83.1+/-3.9, HR (bpm): 66.8+/-4.9,
      both P < 0.05]. Immediately after intubation, the MAP and HR in control group
      were significantly increased as compared with those immediately after anesthesia
      induction [MAP (mmHg): 78.9+/-7.9 vs. 70.0+/-8.7, HR (bpm): 67.3+/-2.7 vs. 60.7+/
      6.7, both P < 0.05], but the changes in MAP and HR in abdominal aorta pressure
      group were not obvious. During the anesthesia induction period, there was no
      statistical difference in SpO2 change between the two groups. During induction of
      anesthesia, no adverse reaction was found in the abdominal aorta pressure group,
      but 4 patients with hypotension and 2 patients with bradycardia were found in the
      control group. Two patients with hypotension were treated with ephedrine, and 2
      patients with bradycardia were treated with atropine. CONCLUSIONS: Anesthesia
      induction of elderly patients with abdominal aorta pressure can help maintain
      hemodynamic stability.

PMID- 28743342
TI  - [Diagnosing value of fasting blood glucose on MODSE caused by pulmonary infection
      in elderly patients with diabetes].
AB  - OBJECTIVE: To evaluate the clinical value of fasting blood glucose (FBG) in the
      diagnosis of multiple organ dysfunction syndrome (MODS) caused by pulmonary
      infection in elderly patients with diabetes. METHODS: Patients over 65 years old
      with diabetic pulmonary infection admitted to Department of Cadres Ward of
      Bethune International Peace Hospital of PLA from July 2015 to December 2016 were
      enrolled. According to the patient's highest FBG level during pulmonary
      infection, all patients were divided in two groups. The cases whose FBG >= 8.83
      mmol/L were served as suspicious multiple organ dysfunction syndrome in the
      elderly (MODSE) group, and those had FBG < 8.83 mmol/L were served as suspicious
      non-MODSE group. The incidence of MODSE in suspicious MODSE group and suspicious
      non-MODSE group was compared. The receiver operating characteristic curve (ROC)
      was drawn, and the clinical value of highest FBG in the diagnosis of MODSE caused
      by pulmonary infection in elderly patients with diabetes was assessed. RESULTS:
      119 elderly patients with diabetes and pulmonary infection were enrolled in the
      analysis. All patients were male, with age of 76-105 years with an average of
      (89.41+/-4.16) years. Among 119 patients, 55 of them with suspected MODSE, 64 of
      them with suspected non-MODSE. The incidence of MODSE in suspicious MODSE group
      was significantly higher than that in suspicious non-MODSE group (78.2% vs.
      12.5%), with statistically significant difference (chi 2 = 52.108, P = 0.000).
      The area under the ROC curve of the highest FBG for diagnosis of MODSE was 0.895,
      and 95% confidence interval (95%CI) was 0.839-0.951 (P < 0.001). When using
      FBG>=8.83 mmol/L to diagnose MODSE induced by pulmonary infection in elderly
      patients with diabetes, the sensitivity was 84.3% and the specificity was 82.4%.
      CONCLUSIONS: FBG>=8.83 mmol/L, as an indicator reflecting the changes of
      metabolic function, have a diagnostic value for MODSE caused by pulmonary
      infection in elderly patients with diabetes.

PMID- 28743343
TI  - [Effects of multimodal combination dialysis on Klotho protein, FGF-23 and BNP in
      patients with maintenance hemodialysis].
AB  - OBJECTIVE: To discuss the effects of multimodal combination dialysis on Klotho
      protein, fibroblast growth factor-23 (FGF-23) and brain natriuretic peptide (BNP)
      in patients with maintenance hemodialysis (MHD). METHODS: A randomized controlled
      trial (RCT) was conducted. 120 patients who was diagnosed with chronic renal
      failure (CRF) uremia receiving MHD over 3 months admitted to Blood Purification
      Centre of Department of Nephrology of the Second People's Hospital of Guiyang
      from December 2015 to December 2016 were enrolled, who were randomly divided into
      hemodialysis (HD) group (HD for 8 times a month), HD + hemofiltration (HF) group
      (HD for 8 times a month + HF once a month), and HD + HF + hemoperfusion (HP)
      group (HD for 8 times a month + HF for 4 times a month + HP once a month), with
      40 patients in each group. Before and after treatment for 6 months and 12 months,
      blood was taken from venous circuit tube, the serum Klotho protein and FGF-23
      levels were determined by enzyme linked immunosorbent assay (ELISA), and the
      serum BNP level was determined by electrochemiluminescence. RESULTS: 120 patients
      with MHD were enrolled in the final analysis without withdrawal. There were no
      significant differences in the levels of Klotho protein, FGF-23, or BNP before
      enrollment among the three groups (all P > 0.05). Compared with those before
      enrollment, the levels of serum Klotho protein after enrollment in three groups
      showed a sustained upward tendency, which were higher in HD + HF + HP group than
      in HD + HF group and HD group (MUg/L: 2.59+/-0.61, 1.63+/-0.35, 1.13+/-0.26 at 6
      months, F = 119.374, P = 0.000; 6.98+/-1.21, 3.57+/-1.03, 2.12+/-0.43 at 12
      months, F = 275.675, P = 0.000); the levels of FGF-23 showed a sustained downward
      tendency, which were lower in HD + HF + HP group than in HD + HF group and HD
      group (ng/L: 69.22+/-38.26, 132.28+/-61.18, 178.50+/-74.64 at 6 months, F =
      33.509, P = 0.000; 32.81+/-17.32, 87.93+/-43.27, 146.33+/-69.28 at 12 months, F =
      55.466, P = 0.000); the BNP showed a similar tendency as FGF-23 (ng/L: 4 083.39+/
      2 864.53, 7 245.69+/-4 643.81, 7 969.12+/-5 360.85 at 6 months, F = 8.758, P =
      0.000; 1 521.86+/-894.63, 4 554.32+/-1 969.84, 5 013.89+/-2 033.64 at 12 months,
      F = 49.003, P = 0.000). CONCLUSIONS: Multimodal combination dialysis can increase
      the Klotho protein level, and decrease the levels of FGF-23 and BNP in MHD
      patients with CRF uremia.

PMID- 28743344
TI  - [Experimental animal study of cerebral oxygen metabolism changes during the
      process of brain death].
AB  - OBJECTIVE: To reproduce a stable animal model of brain death in pigs, observe the
      change regularity of cerebral oxygen metabolism during the process of brain
      death, and to evaluate the significance and value of cerebral oxygen metabolism
      parameters for the diagnosis of brain death. METHODS: Twelve landrace pigs were
      used to create the brain death models using modified method of increasing
      epidural intracranial pressure (ICP). The mean arterial pressure (MAP) and ICP
      were monitored continuously during the process. The pigs were divided into four
      groups according to cerebral perfusion pressure (CPP) decreasing degree during
      brain death, namely CPP normal group and CPP decreasing 0%-30%, 30%-70%, and 70%
      100% groups. Blood gas analysis of the external carotid artery and internal
      jugular vein were monitored discontinuously. The changes in cerebral oxygen
      metabolism parameters, including external carotid artery-internal jugular vein
      bulb oxygen content difference (AJDO2), internal jugular bulb-external carotid
      artery carbon dioxide partial pressure difference (DPCO2) and DPCO2/AJDO2 ratio,
      were observed. RESULTS: Brain death model were successfully reproduced in 12
      experimental pigs. With MAP and ICP monitoring, the models at different stages of
      CPP could be repeatedly induced. The levels of AJDO2 and DPCO2 were increased
      gradually and then decreased, while the ratio of DPCO2/AJDO2 was constantly
      increased with the decrease of CPP. The level of AJDO2 in CPP decreasing 0%-30%
      group was significantly higher than that in CPP normal group [(5.86+/-1.21)% vs.
      (3.92+/-0.64)%], the levels of DPCO2 in CPP decreasing 0%-30% and CPP decreasing
      30%-70% groups were significantly higher than those in CPP normal group [mmHg (1
      mmHg = 0.133 kPa): 10.33+/-1.83, 11.48+/-2.32 vs. 6.11+/-1.43], and the ratios of
      DPCO2/AJDO2 in CPP decreasing 30%-70% and CPP decreasing 70%-100% groups were
      significantly higher than those in CPP normal group and CPP decreasing 0%-30%
      group (2.81+/-0.53, 4.12+/-1.07 vs. 1.57+/-0.64, 1.62+/-0.81). All the
      differences above were statistically significant (all P < 0.05). CONCLUSIONS:
      With the decrease of CPP, cerebral oxygen metabolism showed a regular change
      during brain death. DPCO2 combined with DPCO2/AJDO2 is a reliable blood gas
      analysis index indicating intracranial hypoperfusion, which has certain reference
      value for the determination of brain death.

PMID- 28743345
TI  - [Application of low damage endotracheal intubation in patients undergoing extra
      long-term endotracheal intubation: a case report].
AB  - OBJECTIVE: To approach the effect of low damage endotracheal intubation on
      reducing the occurrence of cuff-related intubation complication and prolonging
      the intubation time. METHODS: On January 7th, 2015, 1 patient with respiratory
      failure after subarachnoid hemorrhage were admitted to Huludao Central Hospital.
      Immediate endotracheal intubation and ventilator assisted ventilation were
      performed. When the trachea was difficult to be removed in a short time, and
      tracheotomy was refused, a low damage endotracheal intubation was used for a long
      term. On the basis of the original high volume low pressure cuff, this tube was
      designed for inner cuff, the hole was allowed in the inner cuff to connect with
      the tube. During the period of ventilation, the cuff pressure changed with airway
      pressure automatically, therefore it would reduce the compression injury of
      tracheal mucosa, improve the tolerance of the patients, and prolong the
      intubation time. RESULTS: The patient was removed from the tube on October 12th,
      2015 with an intubation day of 279, the intubation-related complications and
      severe aspiration pneumonia had not been observed during the application of low
      damage endotracheal intubation. CONCLUSIONS: Design of this intubation ensured
      the cuff pressure changes with airway pressure, therefore, it could effectively
      avoid the cuff pressure become too high, and reduce the occurrence of intubation
      related complication. This low damage endotracheal had an evident superiority in
      the aspects of cuff management. It has a better practical significance,
      especially for patients with long intubation time.

PMID- 28743346
TI  - [Research progress of IQGAP1 in the pathogenesis of ARDS induced by sepsis].
AB  - OBJECTIVE: Sepsis is one of the main cause of patients' death. Lung is the most
      vulnerable target organ during sepsis, and sepsis patients are often complicated
      with acute respiratory distress syndrome (ARDS), of which the main mechanism is
      vascular leakage caused by cytoskeleton rearrangement and cell-to-cell connection
      changes. IQ-guanosine triphosphatease-activating protein 1 (IQGAP1) has become
      the key component of cytoskeleton dynamics regulation in recent years. At
      present, the relationship between IQGAP1 and ARDS induced by sepsis is not yet
      clear. In this article, we will review the mechanism of the interaction between
      IQGAP1 and pathogenic microorganisms, changes of pulmonary micro vascular barrier
      function and cyto-skeleton at the molecular level.

PMID- 28743347
TI  - [Research advances of the role of inflammatory responses in ARDS].
AB  - OBJECTIVE: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an
      inflammatory lung injury induced by a variety of factors, and these diseases are
      associated with high rates of mortality due to the lack of effective treatments.
      Based on the latest research in ALI/ARDS, it is widely accepted that generalized
      inflammatory responses play a critical role in initiating and developing process
      of ALI/ARDS. We make a brief review on the immune-pathogenesis and the signaling
      pathways of ALI/ARDS from the perspective of inflammation, thereby helping
      develop novel therapeutic strategy for treatment of patients with ALI/ARDS.

PMID- 28743348
TI  - [Advances in biomarkers of ARDS].
AB  - OBJECTIVE: Acute respiratory distress syndrome (ARDS) is a common diseases in
      critical ill patients, which is an acute-onset hypoxic condition with
      radiographic bilateral lung infiltration. And it can be divided into two phases
      in pathophysiology: an acute exudative phase combining diffuse alveolar damage
      and lung edema followed by a later fibro proliferative phase. The early
      prediction and risk assessment of patients with ARDS is still very poor in the
      clinical. In recent years, researchers gradually focus their research on
      exploration of biomarkers of ARDS. The article mainly aims to sum up the
      development of biomarkers exploration.

PMID- 28743349
TI  - [Effect of CRRT on the clearance of antibiotics in the treatment of sepsis].
AB  - OBJECTIVE: Sepsis should be defined as life-threatening organ dysfunction caused
      by a dys-regulated host response to infection. Continuous renal replacement
      therapy (CRRT) is one of the methods for the clinical treatment of sepsis. For
      patients undergoing CRRT, rational antimicrobial therapy is very important for
      the control of patient's infection. However, during CRRT, there is no clear
      guideline for the dose adjustment of antibiotics. In this paper, we analyzed the
      effect of CRRT combined with antibiotics on sepsis treatment in China and abroad,
      and discussed its effect on antibiotic clearance, and provided reference for
      clinical work.

PMID- 28743350
TI  - [Advance in the role of innate lymphoid cells in inflammation].
AB  - OBJECTIVE: Innate lymphoid cells (ILCs) are newly identified innate lymphocytes
      in humans and mice that are important and effective cells of innate immunity and
      regulate adaptive immunity. ILCs have been found to promote the start, regulation
      and resolution of inflammation. ILCs play an important role in the progress of
      infection, inflammation and tissue repair in the mouse model, and clinic
      researches also indicate the importance of ILCs in human health and disease.
      Based on the previous related researches, the types of ILCs and the role of these
      populations in promoting acute and chronic inflammation as well as resolution
      inflammation and tissue repair were mainly reviewed to provide new insights for
      the further study.

PMID- 28743352
TI  - ?

PMID- 28743351
TI  - Chronic stress effects and their reversibility on the Fallopian tubes and uterus
      in rats.
AB  - The durational effects of chronic stress on the Fallopian tubes and uterus were
      studied by exposing rats to stressors in the form of restraint (1h) and forced
      swimming (15min) daily for 4, 8 or 12 weeks. One group of stressed rats from each
      time period was then maintained without exposure to stressors for a further 4
      weeks to assess their ability to recover from stress. All time periods of stress
      exposure resulted in decreased weight of the body and Fallopian tubes; however,
      the relative weight of the uterus and serum concentrations of oestradiol and
      insulin increased significantly. The antioxidant potential was decreased with
      increased malondialdehyde concentrations in the Fallopian tubes following all
      durations of exposure and after 4 and 8 weeks of stress exposure in the uterus.
      Interestingly, rats stressed for 12 weeks showed an increase in serum
      testosterone concentration and antioxidant enzyme activities with a decrease in
      malondialdehyde concentration in the uterus. The antioxidant enzyme activities
      and malondialdehyde concentration in the Fallopian tubes of all recovery group
      rats were similar to stressed rats. However, in the uterus these parameters were
      similar to controls in recovery group rats after 4 weeks or 8 weeks of exposure,
      but after 12 weeks of stress exposure these parameters did not return to control
      levels following the recovery period. These results reveal, for the first time,
      that chronic stress elicits an irreversible decrease in antioxidant defence in
      the Fallopian tubes irrespective of exposure duration, whereas the uterus
      develops reversible oxidative stress under short-term exposure but increased
      antioxidant potential with endometrial proliferation following long-term
      exposure.

PMID- 28743353
TI  - Which is the best cutoff of body mass index to identify obesity in female
      patients with rheumatoid arthritis? A study using dual energy X-ray
      absorptiometry body composition.
AB  - INTRODUCTION: Standard anthropometric measures used to diagnose obesity in the
      general population may not have the same performance in patients with rheumatoid
      arthritis. OBJECTIVE: To determine cutoff points for body mass index (BMI) and
      waist circumference (WC) for detecting obesity in women with rheumatoid arthritis
      (RA) by comparing these standard anthropometric measures to a dual-energy X-ray
      absorptiometry (DXA)-based obesity criterion. PATIENTS AND METHOD: Adult female
      patients with more than six months of diagnosis of RA underwent clinical
      evaluation, with anthropometric measures and body composition with DXA. RESULTS:
      Eighty two patients were included, mean age 55+/-10.7 years. The diagnosis of
      obesity in the sample was about 31.7% by BMI, 86.6% by WC and 59.8% by DXA.
      Considering DXA as golden standard, cutoff points were identified for
      anthropometric measures to better approximate DXA estimates of percent body fat:
      for BMI value>=25kg/m2 was the best for definition of obesity in female patients
      with RA, with sensitivity of 80% and specificity of 60%. For WC, with 80% of
      sensitivity and 35% of specificity, the best value to detect obesity was 86cm.
      CONCLUSION: A large percentage of patients were obese. The traditional cutoff
      points used for obesity were not suitable for our sample. For this female
      population with established RA, BMI cutoff point of 25kg/m2 and WC cutoff point
      of 86cm were the most appropriate to detect obesity.

PMID- 28743354
TI  - Analysis of four serum biomarkers in rheumatoid arthritis: association with extra
      articular manifestations in patients and arthralgia in relatives.
AB  - OBJECTIVES: To evaluate the frequency of four serum biomarkers in RA patients and
      their relatives and identify possible associations with clinical findings of the
      disease. METHODS: This was a transversal analytical study. Anti-cyclic
      citrullinated peptide (anti-CCP), anti-mutated citrullinated vimentin (anti-MCV)
      and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex
      agglutination in 210 RA patients, 198 relatives and 92 healthy controls from
      Southern Brazil. Clinical and demographic data were obtained through charts
      review and questionnaires. RESULTS: A higher positivity for all antibodies was
      observed in RA patients when compared to relatives and controls (p<0.0001). IgA
      RF was more frequent in relatives compared to controls (14.6% vs. 5.4%, p=0.03,
      OR=2.98; 95% CI=1.11-7.98) whereas anti-CCP was the most common biomarker among
      RA patients (75.6%). Concomitant positivity for the four biomarkers was more
      common in patients (46.2%, p<0.0001). Relatives and controls were mostly positive
      for just one biomarker (20.2%, p<0.0001 and 15.2%, p=0.016, respectively). No
      association was observed between the number of positive biomarkers and age of
      disease onset, functional class or tobacco exposure. In seronegative patients
      predominate absence of extra articular manifestations (EAMs) (p=0.01; OR=3.25;
      95% CI=1.16-10.66). Arthralgia was present in positive relatives, regardless the
      type of biomarker. CONCLUSIONS: A higher number of biomarkers was present in RA
      patients with EAMs. Positivity of biomarkers was related to arthralgia in
      relatives. These findings reinforce the link between distinct biomarkers and the
      pathophysiologic mechanisms of AR.

PMID- 28743355
TI  - Rheumatoid arthritis and sleep quality.
AB  - BACKGROUND: Sleep disturbances are common in rheumatoid arthritis (RA) patients
      and contribute to loss of life quality. OBJECTIVE: To study associations of sleep
      quality with pain, depression and disease activity in RA. METHODS: This is a
      transversal observational study of 112 RA patients submitted to measurement of
      DAS-28, Epworth scale for daily sleepiness, index of sleep quality by Pittsburg
      index, risk of sleep apnea by the Berlin questionnaire and degree of depression
      by the CES-D (Center for Epidemiologic Studies Depression scale) questionnaire.
      We also collected epidemiological, clinical, serological and treatment data.
      RESULTS: Only 18.5% of RA patients had sleep of good quality. In univariate
      analysis a bad sleep measured by Pittsburg index was associated with daily doses
      of prednisone (p=0.03), DAS-28 (p=0.01), CES-D (p=0.0005) and showed a tendency
      to be associated with Berlin sleep apnea questionnaire (p=0.06). In multivariate
      analysis only depression (p=0.008) and Berlin sleep apnea questionnaire (p=0.004)
      kept this association. CONCLUSIONS: Most of RA patients do not have a good sleep
      quality. Depression and risk of sleep apnea are independently associated with
      sleep impairment.

PMID- 28743356
TI  - Association between body mass index and osteoporosis in women from northwestern
      Rio Grande do Sul.
AB  - OBJECTIVE: To investigate the association between body mass index (BMI) and bone
      mineral density (BMD) in postmenopausal women. METHODS: Observational study with
      postmenopausal women who underwent bone densitometry in Palmeira das Missoes -
      RS. Sociodemographic data, risk for osteoporosis and food intake were assessed
      through a specific form. BMI was calculated according to WHO criteria. The
      assessment of BMD was performed by dual-energy X-ray absorptiometry (DXA) and
      classified according to WHO. Statistical analysis was performed using prevalence
      ratios (PR) and their respective 95% confidence intervals for the factors
      studied. Variables associated with p<0.20 with the different outcomes (osteopenia
      and osteoporosis) were included in a Poisson regression model with robust
      variance to adjust for potential confounding factors. A 5% significance level was
      considered. RESULTS: 393 postmenopausal women with a mean age of 59.6+/-8.2 years
      participated. After the adjustments, the normal weight women had 1.2 times the
      prevalence of osteopenia of obese women (PR=1.2; CI 95% 1.3-1.5). Considering
      osteoporosis, the PR of euthophic women was twice the PR of obese women (PR=2; CI
      95% 1.4-2.9) and was 1.7 times greater for overweight group compared to obese
      category (PR=1.7; CI 95% 1.2-2.5). CONCLUSION: Obese women had lower prevalence
      of osteopenia compared with normal weight subjects and also with lower prevalence
      of osteoporosis as compared to normal- and overweight women.

PMID- 28743357
TI  - Fear-avoidance beliefs increase perception of pain and disability in Mexicans
      with chronic low back pain.
AB  - BACKGROUND: Fear-avoidance beliefs are related to the prognosis of chronicity in
      low back pain in subacute stages, however in chronic pain, is no clear the
      influence of these factors; it has been suggested that the study population can
      determine the magnitude of influence on disability and pain of those suffering
      from back pain. Currently, information does not exist in the Mexican population.
      OBJECTIVE: To analyze the relationship between fear-avoidance beliefs with pain
      and disability in Mexicans with chronic low back pain; analyze potentials
      differences between subgroups according to the time of evolution. METHODS: Cross
      sectional study in Mexicans with chronic LBP aged between 18 and 45. Data were
      collected on general socio demographic characteristics, time of evolution, body
      mass index, pain, disability and fear-avoidance beliefs. RESULTS: 33 men and 47
      women, with an average age of 34.19+/-7.65 years. Higher scores of fear-avoidance
      beliefs were obtained in women (47.2+/-20.99 versus 38.5+/-9.7; p=0.05) and
      single participants (p=0.04). A positive correlation was found between disability
      (r=0.603, p<0.001) and pain (r=0.234, p=0.03) with high scores of fear-avoidance
      beliefs. Through generalized linear models for disability, total score of the
      fear avoidance beliefs questionnaire showed a standardized beta coefficient of
      0.603, p<0.001 (R2 of 0.656); for pain showed a standardized beta coefficient of
      0.29, p=0.01 (R2 of 0.721). CONCLUSION: The present study suggests that there is
      a strong relationship between pain severity, FABQ scores, and functional
      disability in Mexicans with chronic LBP.

PMID- 28743358
TI  - Higher body mass index and anti-drug antibodies predict the discontinuation of
      anti-TNF agents in Korean patients with axial spondyloarthritis.
AB  - OBJECTIVE: The development of anti-drug antibodies against tumor necrosis factor
      inhibitors is a likely explanation for the failure of TNF-inhibitors in patients
      with spondyloarthritis. Our study determined the existence and clinical
      implications of ADAbs in axial spondyloarthritis patients. METHODS: According to
      the Assessment of SpondyloArthritis International Society classification criteria
      for axial spondyloarthritis, patients treated with adalimumab or infliximab were
      recruited consecutively. Serum samples were collected at enrollment to measure
      anti-drug antibodies and drug levels. RESULTS: Of 100 patients, the mean duration
      of current TNF inhibitor use was 22.3+/-17.9 months. Anti-drug antibodies were
      detected in 5 of 72 adalimumab users compared to 5 of 28 infliximab users (6.9%
      vs. 17.9%). Anti-drug antibodies-positive patients had a significantly higher
      body mass index than anti-drug antibodies-negative patients among both adalimumab
      (28.4+/-5.9kg/m2 vs. 24.3+/-2.9kg/m2, respectively, p=0.01) and infliximab users
      (25.9+/-2.8kg/m2 vs. 22.6+/-2.8kg/m2, respectively, p=0.02). During the median 15
      month follow-up period, drug discontinuation occurred more frequently in the anti
      drug antibodies-positive group than the anti-drug antibodies-negative group
      (30.0% vs. 6.5%, respectively, p=0.04). In logistic regression, anti-drug
      antibodies positivity (OR=5.85, 95% CI 1.19-28.61, p=0.029) and body mass index
      (OR=4.35, 95% CI 1.01-18.69, p=0.048) were associated with a greater risk of
      stopping TNF inhibitor treatment. CONCLUSIONS: Our result suggests that the
      presence of anti-drug antibodies against adalimumab and infliximab as well as a
      higher body mass index can predict subsequent drug discontinuation in axial
      spondyloarthritis patients.

PMID- 28743359
TI  - Obesity is the main determinant of insulin resistance more than the circulating
      pro-inflammatory cytokines levels in rheumatoid arthritis patients.
AB  - BACKGROUND: Systemic blockade of TNF-alpha in Rheumatoid arthritis with insulin
      resistance seems to produce more improvement in insulin sensitivity in normal
      weight patients with Rheumatoid arthritis than in obese patients with Rheumatoid
      arthritis, suggesting that systemic-inflammation and obesity are independent risk
      factors for insulin resistance in Rheumatoid arthritis patients. OBJECTIVES: To
      evaluate the insulin resistance in: normal weight patients with Rheumatoid
      arthritis, overweight patients with Rheumatoid arthritis, obese Rheumatoid
      arthritis patients, and matched control subjects with normal weight and obesity;
      and its association with major cytokines involved in the pathogenesis of the
      disease. METHODS: Assessments included: body mass index, insulin resistance by
      Homeostasis Model Assessment, ELISA method, and enzymatic colorimetric assay.
      RESULTS: Outstanding results from these studies include: (1) In Rheumatoid
      arthritis patients, insulin resistance was well correlated with body mass index,
      but not with levels of serum cytokines. In fact, levels of cytokines were similar
      in all Rheumatoid arthritis patients, regardless of being obese, overweight or
      normal weight (2) Insulin resistance was significantly higher in Rheumatoid
      arthritis with normal weight than in normal weight (3) No significant difference
      was observed between insulin resistances of Rheumatoid arthritis with obesity and
      obesity (4) As expected, levels of circulating cytokines were significantly
      higher in Rheumatoid arthritis patients than in obesity. CONCLUSIONS: Obesity
      appears to be a dominant condition above inflammation to produce IR in RA
      patients. The dissociation of the inflammation and obesity components to produce
      IR suggests the need of an independent therapeutic strategy in obese patients
      with RA.

PMID- 28743360
TI  - Signs and symptoms of rheumatic diseases as first manifestation of pediatric
      cancer: diagnosis and prognosis implications.
AB  - OBJECTIVE: To assess the prevalence and describe the clinical, laboratory and
      radiological findings, treatment and outcome of children with cancer initially
      referred to a tertiary outpatient pediatric rheumatology clinic. METHODS:
      Retrospective analysis of medical records from patients identified in a list of
      250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirao
      Preto Medical School hospital, University of Sao Paulo, from July 2013 to July
      2015, whose final diagnosis was cancer. RESULTS: Of 250 patients seen during the
      study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional
      symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially,
      all patients had at least one alteration in their blood count, lactate
      dehydrogenase was increased in 80% and a bone marrow smear was conclusive in 60%
      of patients. Bone and intestine biopsies were necessary for the diagnosis in 2
      patients. JIA was the most common initial diagnosis. The definitive diagnosis was
      acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma,
      and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in
      remission and 2 (40%) died, one of them with prior use of steroids. CONCLUSION:
      The constitutional and musculoskeletal symptoms common to rheumatic and
      neoplastic diseases can delay the diagnosis and consequently worsen the prognosis
      of neoplasms. Initial blood count and bone marrow smear may be normal in the
      initial framework of neoplasms. Thus, the clinical follow-up of these cases
      becomes imperative and the treatment, mainly with corticosteroids, should be
      delayed until diagnostic definition.

PMID- 28743361
TI  - Relapsing polychondritis: prevalence of cardiovascular diseases and its risk
      factors, and general disease features according to gender.
AB  - The comorbidities in relapsing polychondritis have been scarcely described in the
      literature. Moreover, apart from a few relapsing polychondritis epidemiological
      studies, no studies specifically addressing relapsing polychondritis distribution
      according to gender are available. Therefore, the objectives of the present study
      were: (a) to analyze the prevalence of cardiovascular diseases and its risk
      factors in a series of patients with relapsing polychondritis; (b) to determine
      the influence of gender on relapsing polychondritis. A cross-sectional tertiary
      single center study evaluating 30 relapsing polychondritis cases from 1990 to
      2016 was carried out. To compare comorbidities, 60 healthy individuals matched
      for age-, gender-, ethnicity- and body mass index were recruited. The mean age of
      relapsing polychondritis patients was 49.0+/-12.4 years, the median disease
      duration 6.0 years, and 70% were women. A higher frequency of arterial
      hypertension (53.3% vs. 23.3%; p=0.008) and diabetes mellitus (16.7% vs. 3.3%;
      p=0.039) was found in the relapsing polychondritis group, compared to the control
      group. As an additional analysis, patients were compared according to gender
      distribution (9 men vs. 21 women). The clinical disease onset features were
      comparable in both genders. However, over the follow-up period, male patients had
      a greater prevalence of hearing loss, vestibular disorder and uveitis events, and
      also received more cyclophosphamide therapy (p<0.05). There was a high prevalence
      of arterial hypertension and diabetes mellitus, and the male patients seemed to
      have worse prognosis than the female patients in the follow up.

PMID- 28743362
TI  - Critical revision of the medical treatment of gout in Brazil.
AB  - Gout is considered the most common form of inflammatory arthritis in men over 40
      years. The authors present a brief review of the current treatment of gout and
      discuss the existing pharmacological limitations in Brazil for the treatment of
      this disease. Although allopurinol is still the main drug administered for
      decreasing serum levels of uric acid in gout patients in this country, the
      authors also present data that show a great opportunity for the Brazilian drug
      market for the treatment of hyperuricemia and gout and especially for patients
      using private and public (SUS) health care systems.

PMID- 28743363
TI  - Prevalence of fibromyalgia: literature review update.
AB  - The present study aimed to update the literature review on the prevalence of
      fibromyalgia published in 2006. A bibliographical survey was carried out from
      2005 to 2014 in the MEDLINE, Web of Science, Embase, LILACS and SciELO databases
      and 3274 records were identified. Five researchers selected the studies,
      following the inclusion criteria: studies that obtained the prevalence of
      fibromyalgia. Fibromyalgia studies in associated diseases were excluded. When
      screening by title and abstract, 2073 irrelevant articles were excluded. The full
      texts of 210 articles were evaluated for eligibility and this review included 39
      studies, described in 41 articles. The selected studies were grouped into four
      categories: (A) prevalence of fibromyalgia in the general population; (B)
      prevalence of fibromyalgia in women; (C) prevalence of fibromyalgia in rural and
      urban areas; (D) prevalence of fibromyalgia in special populations. The
      literature shows values of fibromyalgia prevalence in the general population
      between 0.2 and 6.6%, in women between 2.4 and 6.8%, in urban areas between 0.7
      and 11.4%, in rural areas between 0.1 and 5.2%, and in special populations values
      between 0.6 and 15%. This literature review update shows a significant increase
      in fibromyalgia prevalence studies in the world. The new 2010 American College of
      Rheumatology criteria have not been widely used yet and the COPCORD (Community
      oriented program for control of Rheumatic Diseases) methodology has increased the
      quality of studies on the prevalence of rheumatic diseases in general.

PMID- 28743364
TI  - Rheumatic fever: update on the Jones criteria according to the American Heart
      Association review - 2015.
AB  - Rheumatic fever is still currently a prevalent disease, especially in developing
      countries. Triggered by a Group A beta-hemolytic Streptococcus infection, the
      disease may affect genetically predisposed patients. Rheumatic carditis is the
      most important of its clinical manifestations, which can generate incapacitating
      sequelae of great impact for the individual and for society. Currently, its
      diagnosis is made based on the Jones criteria, established in 1992 by the
      American Heart Association. In 2015, the AHA carried out a significant review of
      these criteria, with new diagnostic parameters and recommendations. In the
      present study, the authors perform a critical analysis of this new review,
      emphasizing the most relevant points for clinical practice.

PMID- 28743365
TI  - Achilles tendon xanthoma.

PMID- 28743366
TI  - The enzymatic sphingomyelin to ceramide conversion increases the shear membrane
      viscosity at the air-water interface.
AB  - Whereas most of lipids have viscous properties and they do not have significant
      elastic features, ceramides behave as very rigid solid assemblies, displaying
      viscoelastic behaviour at physiological temperatures. The present review
      addresses the surface rheology of lipid binary mixtures made of sphingomyelin and
      ceramide. However, ceramide is formed by the enzymatic cleavage of sphingomyelin
      in cell plasma membranes. The consequences of the enzymatically-driven ceramide
      formation involve mechanical alterations of the embedding membrane. Here, an
      increase on surface shear viscosity was evidenced upon enzymatic incubation of
      sphingomyelin monolayers. The overall rheological data are discussed in terms of
      the current knowledge of the thermotropic behaviour of ceramide-containing model
      membranes.

PMID- 28743367
TI  - Characterization of polychlorinated biphenyl congeners in surface sediments of
      the Changjiang Estuary and adjacent shelf by high-resolution sampling and high
      resolution mass spectrometry.
AB  - Due to limited samples and low-resolution analysis, conflicting findings on major
      polychlorinated biphenyl (PCB) congeners and their origins remain in the East
      China Sea (ECS). Based on high-resolution sampling and high-resolution mass
      spectrometry analysis, 72 surface sediment samples from the Changjiang Estuary
      and adjacent ECS shelf were determined to characterize 39 PCB congeners. PCBs
      (?39PCBs) ranged from 0.003 to 16.18ng/g dw, presenting a decreasing seaward
      trend. Tri-, tetra- and penta-CBs were the main components, accounting for >64%
      of ?39PCBs in most samples. Tetra-CBs were the dominant congeners, corresponding
      to results of sediments from Changjiang middle reach and soils from Changjiang
      Delta. Comparison between PCBs and sediment properties indicated there may be a
      deposition boundary of 30 degrees N. In the north, the spatial distribution of
      PCBs is controlled by Changjiang input and hydrodynamic conditions, while in the
      south closely related to combination of local source and riverine input.

PMID- 28743368
TI  - Chemoreception drives plastic consumption in a hard coral.
AB  - The drivers behind microplastic (up to 5mm in diameter) consumption by animals
      are uncertain and impacts on foundational species are poorly understood. We
      investigated consumption of weathered, unfouled, biofouled, pre-production and
      microbe-free National Institute of Standards plastic by a scleractinian coral
      that relies on chemosensory cues for feeding. Experiment one found that corals
      ingested many plastic types while mostly ignoring organic-free sand, suggesting
      that plastic contains phagostimulents. Experiment two found that corals ingested
      more plastic that wasn't covered in a microbial biofilm than plastics that were
      biofilmed. Additionally, corals retained ~8% of ingested plastic for 24h or more
      and retained particles appeared stuck in corals, with consequences for
      energetics, pollutant toxicity and trophic transfer. The potential for
      chemoreception to drive plastic consumption in marine taxa has implications for
      conservation.

PMID- 28743369
TI  - Quality of life is significantly associated with survival in women with advanced
      epithelial ovarian cancer: An ancillary data analysis of the NRG
      Oncology/Gynecologic Oncology Group (GOG-0218) study.
AB  - OBJECTIVE: Evaluate association between baseline quality of life (QOL) and
      changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and
      overall survival (OS) in advanced epithelial ovarian cancer (EOC). METHODS:
      Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline
      and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores
      were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with
      log-rank statistic and multivariate Cox regression adjusting for age, stage, post
      surgical residual disease size, and performance status (PS). Trends in FACT-O TOI
      scores from baseline to the latest follow-up assessment were evaluated for impact
      on intragroup (Q1 or Q2-4) outcome by log-rank analysis. RESULTS: Of 1152
      eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI
      scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P<0.001). Q1 compared to Q2-4 had
      worse median OS (37.5 vs. 45.6months, P=0.001) and worse median PFS (12.5 vs.
      13.1months, P=0.096). Q2-4 patients had decreased risks of disease progression
      (HR 0.974, 95% CI 0.953-0.995, P=0.018), and death (HR 0.963, 95% CI 0.939-0.987,
      P=0.003) for each five-point increase in baseline FACT-O TOI. Improving versus
      worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1:
      12.7 vs. 8.6months, P=0.001; Q2-4: 16.7 vs. 11.1months, P<0.001) and median OS
      (Q1: 40.8 vs. 16months, P<0.001; Q2-4: 54.4 vs. 33.6months, P<0.001).
      CONCLUSIONS: Baseline FACT-O TOI scores were independently prognostic of PFS and
      OS while improving compared to worsening QOL was associated with significantly
      better PFS and OS in women with EOC.

PMID- 28743370
TI  - Computational and clinical investigation on the role of mechanical vibration on
      orthodontic tooth movement.
AB  - The aim of this study is to investigate the biomechanics for orthodontic tooth
      movement (OTM) subjected to concurrent single-tooth vibration (50Hz) with
      conventional orthodontic force application, via a clinical study and
      computational simulation. Thirteen patients were recruited in the clinical study,
      which involved distal retraction of maxillary canines with 1.5N (150g) force for
      12weeks. In a split mouth study, vibration and non-vibration sides were randomly
      assigned to each subject. Vibration of 50Hz, of approximately 0.2N (20g) of
      magnitude, was applied on the buccal surface of maxillary canine for the
      vibration group. A mode-based steady-state dynamic finite element analysis (FEA)
      was conducted based on an anatomically detailed model, complying with the
      clinical protocol. Both the amounts of space closure and canine distalization of
      the vibration group were significantly higher than those of the control group, as
      measured intra-orally or on models (p<0.05). Therefore it is indicated that a
      50Hz and 20g single-tooth vibration can accelerate maxillary canine retraction.
      The volume-average hydrostatic stress (VHS) in the periodontal ligament (PDL) was
      computationally calculated to be higher with vibration compared with the control
      group for maxillary teeth and for both linguo-buccal and mesial-distal
      directions. An increase in vibratory frequency further amplified the PDL response
      before reaching a local natural frequency. An amplification of PDL response was
      also shown to be induced by vibration based on computational simulation. The
      vibration-enhanced OTM can be described by mild, vigorous and diminishing zones
      among which the mild zone is considered to be clinically beneficial.

PMID- 28743371
TI  - Empyema necessitatis caused by Corynebacterium jeikeium: 19th century questions,
      21st century answers.

PMID- 28743372
TI  - Is Thoracic Ultrasonography Necessary in the Respiratory Medicine Outpatient
      Clinic?

PMID- 28743373
TI  - Is radioiodine ablation necessary for patients with low-risk papillary thyroid
      carcinoma and tumor >4 cm?

PMID- 28743374
TI  - A systematic review of generic and breast cancer specific life expectancy models
      in the elderly.
AB  - INTRODUCTION: The use of primary endocrine therapy (PET) in managing breast
      cancer in the elderly has become common practice. Whilst there appears to be no
      difference in overall survival in comparison with surgery, PET has been found to
      be inferior in local disease control with a limited duration of efficacy (2-3
      years). The International Society of Geriatric Oncology (SIOG) state that PET may
      be considered in patients with a short life expectancy (<2 years) or considered
      unfit for surgery. Frequently, decision making for PET allocation is a subjective
      process by the clinician. METHOD: A systematic literature review was performed to
      establish what prediction models are available for all-cause mortality in the
      elderly, and what breast-specific models have been produced. RESULTS: 18
      prognostic models were deemed eligible from 15 papers. 1 breast-specific model
      was found, 2 nursing home related and 15 for community-dwelling elders. Accuracy
      (as defined by discrimination; c-statistic or AUROC) ranged from 0.69 (moderate)
      to 0.86 (very good). CONCLUSIONS: This review highlighted a variety of validated
      prognostic indexes. Several models with very good accuracy were identified but
      most were validated in US-populations and relied on information from
      administrative datasets. One breast specific model by Stotter et al. was
      identified, specifically to aid treatment planning for frail elderly patients but
      had limited accuracy. The strength of an index will ultimately be on its clinical
      impact and influence on treatment decisions rather than its accuracy and as of
      yet no trials exploring this have been carried out.

PMID- 28743375
TI  - A Model-Based Prediction of the Probability of Hepatocellular Adenoma and Focal
      Nodular Hyperplasia Based on Characteristics on Contrast-Enhanced Ultrasound.
AB  - Contrast-enhanced ultrasound (CEUS) is an emerging imaging technique that is
      increasingly used to diagnose liver lesions. It is of the utmost importance to
      differentiate between the two most common solid focal liver lesions (i.e.,
      hepatocellular adenoma [HCA] and focal nodular hyperplasia [FNH]), because their
      management and follow-up differ greatly. The main objective of this study was to
      determine how frequently the specific CEUS features of HCA and FNH are visible on
      CEUS and to define their predictive value for discrimination between HCA and FNH.
      We included 324 CEUS examinations performed on patients with FNH (n = 181) or HCA
      (n = 143). Patients with HCA and FNH significantly differed with respect to age
      and CEUS features of steatosis, echogenicity, homogeneity, the presence of a
      central scar, central artery, arterial enhancement pattern, necrosis or thrombus
      and enhancement in the late venous phase.

PMID- 28743376
TI  - Spatio-temporal Image Correlation (STIC): Estimation of Heart Rate Using STIC
      Compared with 2-D Pulsed Wave Doppler in a Flow Phantom.

PMID- 28743377
TI  - Erratum to "Absolute venomics: Absolute quantification of intact venom proteins
      through elemental mass spectrometry".

PMID- 28743378
TI  - Long-term cost-effectiveness of lipid formulations of amphotericin B in the
      empirical therapy of invasive mycosis in a developing country.

PMID- 28743379
TI  - A novel, hydroxyapatite-based screw-like device for anterior cruciate ligament
      (ACL) reconstructions.
AB  - BACKGROUND: Rupture of the anterior cruciate ligament (ACL) is one of the most
      common injuries of the knee. Common techniques for ACL reconstruction require a
      graft fixation using interference screws. Nowadays, these interference screws are
      normally made of titanium or polymer/ceramic composites. The main challenge of
      application of a fixation device made entirely of bioactive ceramic is in
      relation to the low strength of such materials. The purpose of this study was to
      evaluate a novel geometry for a fixation device made of pure hydroxyapatite for
      ACL reconstructions that can overcome some problems of the titanium and the
      polymer/ceramic screws. METHODS: Finite Element Analysis was used for
      optimization of the stress distribution in conventional interference screw
      geometry. For experimental evaluation of the new fixation device, ex vivo tests
      were performed. RESULTS: The innovative screw-like fixation device is
      characterized by multiple threads with a large thread pitch. The novel design
      enabled the insertion of the screw into the bone without the application of an
      external torque or a screwdriver. In turn, it also allowed for the use of low
      strength and high-bioactivity materials, like hydroxyapatite. Ex vivo tests
      showed that the novel screw can sustain pull-out forces up to 476 N, which is
      comparable to that of the commercially available BioCompositeTM interference
      screws (Arthrex Inc., Germany), as a reference. CONCLUSIONS: In summary, the
      novel screw design is a promising strategy to develop all-ceramic fixation
      devices for ACL reconstructions, which may eliminate some drawbacks of the
      current interference screws.

PMID- 28743380
TI  - Emerging Insights into the Functions of Pathogenesis-Related Protein 1.
AB  - The members of the pathogenesis-related protein 1 (PR-1) family are among the
      most abundantly produced proteins in plants on pathogen attack, and PR-1 gene
      expression has long been used as a marker for salicylic acid-mediated disease
      resistance. However, despite considerable interest over several decades, their
      requirement and role in plant defence remains poorly understood. Recent reports
      have emerged demonstrating that PR-1 proteins possess sterol-binding activity,
      harbour an embedded defence signalling peptide, and are targeted by plant
      pathogens during host infection. These studies have re-energised the field and
      provided long-awaited insights into a possible PR-1 function. Here we review the
      current status of PR-1 proteins and discuss how these recent advances shed light
      on putative roles for these enigmatic proteins.

PMID- 28743381
TI  - A novel systematic inflammation related index is prognostic in curatively
      resected non-metastatic colorectal cancer.
AB  - BACKGROUD: To better identify patients with high mortality risk, we developed a
      systematic inflammation index (IPI) based on neutrophil to lymphocyte ratio (NLR)
      and albumin. METHODS: The performance of pretreatment IPI was evaluated in
      patients with surgically resected non-metastatic colorectal cancer. IPI was
      predefined and compared with Glasgow Prognostic Score (GPS)/modified GPS in terms
      of discrimination and calibration abilities. RESULTS: In multivariate analysis,
      patients with an IPI of 1 or 2 had 1.68(95%CI:1.15-2.44) or 3.56(95%CI:2.12-5.98)
      fold increased cancer specific mortality risk(CSMR) respectively in comparison to
      patients with an IPI of 0. The prognostic significance was independent of tumor
      locations and nodal status. Compared with the GPS/mGPS, IPI had the higher c
      statistics and lower Akaike Information Criterion. IPI showed good calibration in
      predicting 1-year, 3-year and 5-year CSMR. CONCLUSIONS: IPI is readily available,
      independently prognostic and may reflect the host inflammation, immune and
      nutritional status that could have impact on cancer progression.

PMID- 28743382
TI  - Preoperative echocardiographic measures of left ventricular mechanics are
      associated with postoperative vasoactive support in preterm infants undergoing
      patent ductus arteriosus ligation.
AB  - OBJECTIVE: Preoperative risk factors associated with poor outcomes after patent
      ductus arteriosus ligation in preterm infants have not been well defined. The aim
      of this study was to determine the association between preoperative
      echocardiographic measures of left ventricular mechanics and postoperative
      clinical outcomes after patent ductus arteriosus ligation. METHODS: Preterm
      infants less than 90 days of age with no other significant congenital anomalies
      who underwent patent ductus arteriosus ligation between 2007 and 2015 were
      considered for retrospective analysis. The primary outcome was peak postoperative
      vasoactive inotropic score. Conventional echocardiographic measures of
      ventricular size, function, and patent ductus arteriosus size were performed.
      Echocardiographic single-beat, pressure-volume loop analysis estimates of
      contractility (end-systolic elastance) and afterload (arterial elastance) were
      calculated. Ventriculoarterial coupling was assessed using the arterial
      elastance/end-systolic elastance ratio. Multivariable linear regression was
      performed using clinical and echocardiographic data. RESULTS: Echocardiograms
      from 101 patients (42.5% male) were analyzed. We found a statistically
      significant association between vasoactive inotropic score and both end-systolic
      elastance and arterial elastance. No patient with arterial elastance/end-systolic
      elastance greater than 0.78 (n = 32) had a vasoactive inotropic score 20 or
      greater. Analysis of our secondary outcomes found associations between
      preoperative end-systolic elastance and postoperative urine output less than 1
      mL/kg/h at 24 hours, creatinine change greater than 0.5 mg/dL, and time to first
      extubation. CONCLUSIONS: End-systolic elastance and arterial elastance were the
      only predictors of postoperative vasoactive inotropic score after patent ductus
      arteriosus ligation in preterm infants. Those neonates with increased
      contractility and low afterload were at highest risk for elevated inotropic
      support. These findings suggest a role for echocardiographic end-systolic
      elastance and arterial elastance in the preoperative assessment of preterm
      infants undergoing patent ductus arteriosus ligation.

PMID- 28743383
TI  - Successful atrioventricular valve repair improves long-term outcomes in children
      with unbalanced atrioventricular septal defect.
AB  - BACKGROUND: Atrioventricular valve regurgitation is a significant cause of
      morbidity and mortality in patients with unbalanced atrioventricular septal
      defect. However, knowledge of the outcomes of atrioventricular valve repair in
      children with unbalanced atrioventricular septal defect and univentricular
      physiology is limited. METHODS: We conducted a retrospective review of all
      patients with unbalanced atrioventricular septal defect treated with single
      ventricle palliation who underwent atrioventricular valve surgery at The Royal
      Children's Hospital. RESULTS: Between 1976 and 2016, 139 children with unbalanced
      atrioventricular septal defect underwent single-ventricle palliation, of whom
      31.7% (44/139) required atrioventricular valve surgery. Repair of the
      atrioventricular valve was attempted in 97.7% (43/44) of patients, of whom 4.7%
      (2/43) were converted to replacement during the initial operation. Replacement of
      the atrioventricular valve without attempted repair was performed in 2.3% (1/44)
      of patients. Early mortality was 18.2% (8/44). Freedom from death or
      transplantation at 10 years was 66.0% (95% confidence interval, 49.1-78.5) and at
      20 years was 53.3% (95% confidence interval, 32.1-70.6). In multivariable
      analysis, significant predischarge atrioventricular valve regurgitation (hazard
      ratio, 6.4; P = .002), age less than 1 year (hazard ratio, 8.3; P = .01), and
      repair before stage II palliation (hazard ratio, 3.4; P = .04) were associated
      with death. Freedom from reoperation at 10 years was 61.9% (95% confidence
      interval, 41.9-76.8) and at 20 years was 56.3% (95% confidence interval, 35.3
      72.8). Moderate or greater atrioventricular valve regurgitation at discharge was
      associated with an increased risk of reoperation (hazard ratio, 1.8; P = .03). Of
      transplant-free survivors, atrioventricular valve regurgitation was less than
      moderate in 60.0% (15/25) at the most recent follow-up. CONCLUSIONS:
      Atrioventricular valve surgery in patients with unbalanced atrioventricular
      septal defect is associated with substantial mortality and a high rate of
      reoperation. Successful atrioventricular valve repair is associated with better
      survival and freedom from reoperation.

PMID- 28743384
TI  - Publication Ethos in the immunogenetics community.

PMID- 28743385
TI  - Corrigendum to "CD28 and PTPN22 are associated with susceptibility to rheumatoid
      arthritis in Egyptians" [Hum. Immunol. 77 (2016) 522-526].

PMID- 28743386
TI  - Corrigendum to "Calculated panel reactive antibody with decimals: A refined
      metric of access to transplantation for highly sensitized candidates" [Hum.
      Immunol. 78(3) (2017) 252-256].

PMID- 28743387
TI  - Polymerase chain reaction based detection of bacterial 16S rRNA gene in the
      cerebrospinal fluid in the diagnosis of bacterial central nervous system
      infection in the course of external cerebrospinal fluid drainage. Comparison with
      standard diagnostics currently used in clinical practice.
AB  - BACKGROUND AND PURPOSE: External drainage of cerebrospinal fluid (CSF) is a
      commonly used neurosurgical procedure. Complications of the procedure comprise
      central nervous system (CNS) bacterial infections, the frequency of which is
      estimated at around 6-10%. Detection of these infections is ineffective in many
      cases. The aim of the study was to evaluate the usefulness of a polymerase chain
      reaction (PCR)-based detection of bacterial 16S rRNA gene (16S rDNA) in the CSF.
      MATERIAL AND METHODS: The study group consisted of 50 patients. Clinical signs of
      CNS infection were monitored and routine laboratory and microbiological tests
      were performed. The results of standard methods were compared with the bacterial
      16S rDNA detection. RESULTS: Using cultures, CNS infection was diagnosed in 8
      patients, colonization of the drainage catheter in 6 patients, and sample
      contamination in 7 patients. In the group of the remaining 29 patients, no
      positive CSF culture was obtained and 13 of these patients also had all negative
      results for 16S rDNA detection. For the remaining 16 patients of this group, CNS
      infection, colonization of the catheter and sample contamination were diagnosed
      via PCR alone. Routine biochemical CSF tests and blood inflammatory parameters
      had a supporting value. CONCLUSIONS: Routine hospital tests do not provide rapid
      and efficient detection of the external drainage related bacterial CNS infection.
      It is justified to use several diagnostic methods simultaneously. The16S rDNA
      determination in CSF can increase the probability of detection of possible
      pathogens.

PMID- 28743388
TI  - Traumatic bilateral dissection of cervical internal carotid artery in the wake of
      a car accident: A case report.
AB  - BACKGROUND: Bilateral carotid artery dissection secondary to severe trauma is
      rare and can be potentially life -threatening if not diagnosed and treated
      properly. CASE PRESENTATION: We report a 29-year-old female who was admitted to
      the emergency department after a car accident. The patient was conscious at the
      time of admission and presented with an initial Glasgow Coma Scale (GCS) of 15
      presenting normal vital signs. The patient developed motor dysphasia with right
      upper limb paresis a few hours after the admission. Magnetic resonance imaging
      (MRI) revealed a bilateral cervical internal carotid artery (ICA) occlusion in
      addition to left frontal lobe infarct in a subacute phase. Medical management was
      successful and the patient was discharged from the hospital two weeks after the
      admission. DISCUSSION: Noninvasive vascular imagining modalities are merging as
      the gold standard in the early detection of carotid artery dissection (CAD).
      Typical pathognomonic findings on MRI include double lumen and intimal flap. The
      management with systemic anticoagulation or antiplatelet therapy is aimed to
      prevent the development of ischemic stroke. In case of medical therapy being
      ineffective or in case of complication or any disorders suffered by a patient,
      endovascular treatment is performed. CONCLUSION: With early detection and proper
      management, traumatic dissection of cervical carotid artery can have a benign
      outcome. As for the current patient, medical treatment with anticoagulation was
      sufficient and surgical management was therefore not required. Improvement in the
      patients' speech was observed; nevertheless the continuation of speech therapy
      was indicated.

PMID- 28743389
TI  - Cerebrospinal fluid leakage and Chiari I malformation with Gorham's disease of
      the skull base: A case report.
AB  - BACKGROUND: Gorham's syndrome is a rare bone disorder characterized by massive
      osteolysis of unknown etiology. There are no reports of comorbidity involving
      cerebrospinal fluid (CSF) leakage and Chiari I malformation with Gorham's
      syndrome. Here, we report an unusual case of an acute presyrinx state complicated
      by bacterial meningitis due to CSF leakage and Chiari I malformation associated
      with Gorham's disease of the skull base. CASE PRESENTATION: A 25-year-old woman
      with Chiari I malformation associated with Gorham's syndrome presented with
      aggressive paresthesia following bacterial meningitis. Axial magnetic resonance
      imaging (MRI) and computed tomography (CT) cisternography revealed CSF leakage in
      the right petrous apex. A presyrinx state was diagnosed based on the clinical
      symptoms and MRI findings. With resolution of the bacterial meningitis, the
      spinal edema and tonsillar ectopia also improved. Surgical repair of the CSF
      leakage was performed by an endoscopic endonasal transsphenoidal approach to
      prevent recurrence of meningitis. The postoperative course was uneventful.
      CONCLUSION: Skull base osteolysis in Gorham's syndrome may induce Chiari I
      malformation and CSF leakage. We should pay attention to acute progression of
      clinical symptoms because Gorham's syndrome may predispose to development of
      Chiari I malformation and may be complicated by CSF leakage.

PMID- 28743390
TI  - Baicalin attenuates in vivo and in vitro hyperglycemia-exacerbated
      ischemia/reperfusion injury by regulating mitochondrial function in a manner
      dependent on AMPK.
AB  - Cerebral ischemia/reperfusion (I/R) is a lethal and disabling disease. Studies
      have suggested that hyperglycemia is a risk factor for cerebral I/R. Baicalin is
      a natural bioactive flavonoid extracted from Scutellaria baicalensis Georgi with
      neuroprotective activity. In the present study, we investigated the effects of
      baicalin on hyperglycemia-exacerbated cerebral I/R injury. Streptozotocin (STZ)
      injection aggravated the brain damage induced by middle cerebral artery occlusion
      (MCAO) surgery, while baicalin administration reduced blood glucose, relieved
      neurological deficit and decreased infarct volume. In vitro, Oxygen-glucose
      deprivation/ reperfusion (OGD/REP) induced inordinate reactive oxygen species
      (ROS) production and mitochondrial dynamic impairments were markedly increased
      under high glucose (HG) condition. Baicalin treatment in PC12 cells inhibited
      dynamin-related protein 1 (Drp-1) expression, decreased mitochondrial fission,
      promoted mitofusin-2 (MFN2) generation, increased Drp-1 Ser637 phosphorylation,
      and elevated mitochondrial membrane potential (Deltapsim) via the suppression of
      ROS production. However, AMPKalpha1 knockdown abolished the protective effects of
      baicalin. Baicalin also suppressed cell apoptosis and enhanced mitophagy. These
      results suggested that baicalin protected against hyperglycemia aggravated I/R
      injury by regulating mitochondrial functions in a manner dependent on AMPK.

PMID- 28743391
TI  - Valporic acid enhances the Atrial Natriuretic Peptide (ANP) mediated anti
      hypertrophic activity by modulating the Npr1 gene transcription in H9c2 cells in
      vitro.
AB  - The present study was aimed to determine whether stimulating Npr1 gene activity
      using Valporic acid (VA), a small short chain fatty acid molecule can enhance ANP
      mediated anti-hypertrophic activity in isoproterenol (ISO) - treated H9c2 cells
      in vitro. H9c2 cells were treated with ISO (10-5 M) and co-treated with VA (10-5
      M) in the presence and absence of ANP (10-8M), for 48h. ATRA (10-5 M) was used as
      a positive inducer of Npr1 gene transcription. The mRNA expression of Npr1 and
      PKG-I genes, proto-oncogenes (c-fos, c-jun and c-myc) and hypertrophic markers
      (ANP, BNP, alpha-sk and beta-MyHC), genes were determined by quantitative PCR
      (qPCR). The protein profiling of NPR-A, PKG-I and cGMP were evaluated by Western
      blot, immunofluorescence and ELISA respectively. A marked reduction in the level
      of expression of Npr1 (3- fold) and PKG-I (2.5-fold) genes and increased
      expression of proto-oncogenes (p< 0.001, respectively) and hypertrophic marker
      genes (p<0.001, respectively) were noticed in the ISO-treated H9c2 cells as
      compared with control cells. In contrast, the VA treated cells showed maximal
      Npr1 gene expression (3.5-fold) as compared with ATRA treated cells (2 fold),
      which is well correlated with the intracellular cGMP levels (80% vs 60%) and
      reduced (2.5-fold) HDAC -1&-2 mRNA expression. Furthermore, VA or ATRA treatment
      effectively reversed the ISO-induced altered expression of Npr1 and PKG-I genes,
      proto-oncogenes, and hypertrophic markers genes. Interestingly, the results of
      the present study suggest that ANP mediated anti-hypertrophic activity was
      enhanced with either VA (p<0.001) or ATRA (p<0.01) co-treatment. Together, we
      conclude that VA in combination with ANP can be a novel therapeutical approach
      for the treatment and management of left ventricular cardiac hypertrophy.

PMID- 28743392
TI  - Fully international system of units-traceable glycated hemoglobin quantification
      using two stages of isotope-dilution high-performance liquid chromatography
      tandem mass spectrometry.
AB  - Glycated hemoglobin (HbA1c), defined as hemoglobin (Hb) molecules having a stable
      adduct of glucose on the N-terminal of the beta-chains, has been endorsed as a
      diagnostic tool for diabetes mellitus and a prediction indicator for the
      development of diabetes complications. Here we describe an accurate procedure
      using two stages of isotope dilution-ultra performance liquid chromatography
      tandem mass spectrometry (ID-LC-MS/MS) for the quantification of HbA1c that
      provides full traceability to International System of Units (SI). First,
      synthetic peptides representing specific markers of HbA1c (G-hexa) and hemoglobin
      A0 (Hexa) were certified by amino acid analysis via acid hydrolysis as reference
      materials (RMs) for the next step. For this peptide certification, three amino
      acids (proline, valine, and leucine) were determined by hydrolysis with 10M
      hydrochloric acid at 130 degrees C for 48h followed by ID-LC-MS/MS. Then, HbA1c
      content in blood was quantified with the ratio of specific proteolytic peptides
      from HbA1c and HbA0 via enzyme digestion using ID-LC-MS/MS with the certified
      peptides as RMs and isotope-labeled peptides as internal standards. Results
      demonstrate complete traceability to SI-units throughout this procedure.
      Reliability was confirmed through comparative studies with commercially available
      RMs for HbA1c, and other routine HbA1c diagnostic methods as well. Following full
      method validation, we applied this procedure to the certification of candidate
      hemolysate-certified RMs for HbA1c content, as well as 52 real clinical samples.
      All of the results showed the suitability of this method to act as a primary
      reference measurement procedure for HbA1c in complex biological samples.

PMID- 28743393
TI  - Considerations for the use of ultra-high pressures in liquid chromatography for
      2.1mm inner diameter columns.
AB  - The current contribution investigates the effects of viscous heat dissipation in
      chromatographic columns (with an emphasis on so-called narrow bore columns with
      an inner diameter of 2.1mm) using numerical simulations of the temperature and
      velocity profiles and the resulting band broadening, for the first time at
      operating pressures up to 2000bar. When operating columns under well
      thermostatted conditions to maintain a constant temperature of the mobile phase,
      a dramatic increase in plate heights can be observed that voids any advantage one
      could expect from the possibility to use smaller particles offered by the
      increased pressure limit. It is also clearly demonstrated that, even when the
      column is not temperature controlled, the backflow of heat along the wall can
      causes a significant loss in performance under standard operating conditions in a
      still air oven. It is found that for operating pressure above 1250bar, a
      significant (relative to the typical column performance) contribution to the
      observed plate height will be caused by viscous heating effects, which increases
      with increasing temperature dependency of the retention factor. In addition,
      unprecedented experimental measurements of the temperature effects at an
      operating pressure up to 2600bar were performed on a 10cm long, 2.1mm ID column
      showing a dramatic temperature increase up to 60 degrees C relative to the inlet
      temperature when using methanol as a mobile phase.

PMID- 28743394
TI  - Optimal mixing rate in reverse phase liquid chromatography. Experimental
      evaluations.
AB  - The topic of this report is experimental verification of previously published
      theoretical predictions. The mixing rate (Rphi) is the temporal rate of
      increasing a fraction of stronger solvent in the mobile phase of gradient LC. The
      optimal Rphi (Rphi,Opt) is the one at which a required peak capacity (n) of
      gradient LC analysis is obtained in the shortest time. The key factors affecting
      Rphi,Opt are the sample molecular weight (M), the void time (tM), and the column
      pressure condition - Rphi,Opt in a column operating below the instrumental
      pressure limit is 2-3 times higher than Rphi,Opt in a column operating at the
      instrumental pressure limit. Using previously proposed speed optimization
      criteria, t/si, where t, s and i are the analysis time, the separation capacity
      (a metric proportions to n), and the order (i=2 or i=4 for analyses operating
      below or at the instrumental pressure limit, respectively), parameter Rphi,Opt
      for analyses of small-molecule samples has been experimentally found. For both
      orders, the agreement with the theoretical prediction can be considered as very
      good. Base on the experimental results, we continue to recommend the earlier
      proposed theoretically based mixing rate of 5%/tM as a default for all analyses
      of small-molecule samples (100<M<400), and 50%3/M/tM for larger molecules.
      Experimental evidence is also provided to explain why earlier published less
      accurate equations for peak capacity and analysis time are not suitable for
      theoretical prediction of Rphi,Opt.

PMID- 28743395
TI  - Biomonitoring of fluoroalkylated substances in Antarctica seabird plasma:
      Development and validation of a fast and rugged method using on-line
      concentration liquid chromatography tandem mass spectrometry.
AB  - We report on a fast, accurate and rugged analytical procedure to determine a wide
      span of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in seabird plasma.
      The 26 investigated compounds included perfluoroalkyl carboxylates (C5-C14
      PFCAs), perfluoroalkyl sulfonates (C4, C6, C7, C8, C10 PFSAs), perfluorooctane
      sulfonamide (FOSA) and N-alkyl derivatives (MeFOSA, EtFOSA), N-alkyl
      perfluorooctane sulfonamido acetic acids (MeFOSAA, EtFOSAA), fluorotelomer
      sulfonates (4:2 FTSA, 6:2 FTSA, 8:2 FTSA), polyfluoroalkyl phosphate diesters
      (diPAPs) and perfluorooctane sulfonamide phosphate diester (diSAmPAP). The method
      described herein requires a reduced sample amount (25MUL) and involves rapid and
      simple sample preparation (protein precipitation with acetonitrile but without
      acidification) prior to analysis by on-line solid phase extraction (Oasis HLB
      sorbent) coupled to high performance liquid chromatography negative electrospray
      ionization tandem mass spectrometry. The optimization was conducted using
      experimental designs to account for potential interactions between variables. Out
      of the 26 target analytes, 23 compounds showed excellent accuracy (+/-25% of the
      expected values). Intermediate precision and matrix effects remained acceptable
      for most analytes thanks to efficient internal standardization. A human serum
      standard reference material (NIST SRM 1957) was included in the validation scheme
      to evaluate method trueness, which proved satisfactory (?Z-scores?<2 for most
      compounds). Notwithstanding the small initial sample intake, limits of detection
      as low as 0.003-0.1ngg-1 plasma were obtained. This allowed the determination of
      11 target PFASs in Antarctic seabird plasma samples. SigmaPFASs in Antarctic
      seabird plasma ranged from 0.37 to 19ngg-1, with a predominance of PFOS (>54% of
      SigmaPFASs on average). The reduced plasma amount required implies that the
      present method could also be applied to the analysis of PFASs in the plasma of
      smaller biological models.

PMID- 28743397
TI  - Precision Medicine: precisely now.

PMID- 28743396
TI  - Synthesis of hydrogel via click chemistry for DNA electrophoresis.
AB  - This work introduces a novel sieving gel for DNA electrophoresis using a
      classical click chemistry reaction, the copper (I)-catalyzed azide-alkyne
      cycloaddition (CuAAC), to cross-link functional polymer chains. The efficiency of
      this reaction provides, under mild conditions, hydrogels with near-ideal network
      connectivity and improved physical properties. Hydrogel formation via click
      chemistry condensation of functional polymers does not involve the use of toxic
      monomers and UV initiation. The performance of the new hydrogel in the separation
      of double stranded DNA fragments was evaluated in the 2200 TapeStation system, an
      analytical platform, recently introduced by Agilent that combines the advantages
      of CE in terms of miniaturization and automation with the simplicity of use of
      slab gel electrophoresis. The click gel enables addition of florescent dyes prior
      to electrophoresis with considerable improvement of resolution and separation
      efficiency over conventional cross-linked polyacrylamide gels.

PMID- 28743398
TI  - Weight loss and abdominal pain in a young woman: Gastric trichobezoar.

PMID- 28743399
TI  - Educational intervention on cardiovascular parameters in perimenopausal women
      with a cardiovascular risk factor. Randomised clinical trial.
AB  - BACKGROUND AND OBJECTIVE: Randomised clinical trial performed in two urban health
      centres in Spain. To evaluate if educational intervention in women of
      perimenopausal age with hypertension, diabetes mellitus and/or dyslipidaemia
      could achieve significant changes in the reduction of biochemical and
      haemodynamic risk parameters. PATIENTS AND METHODS: The study included 320 women
      aged between 45 and 60 years old who were diagnosed with hypertension, diabetes
      mellitus and/or dyslipidaemia. They were randomly assigned to the experimental
      group (n=160) and the control group (n=160). The intervention group received
      three educational sessions and the control group received an informative leaflet
      sent by mail. Haemodynamic and biochemical variables were evaluated at baseline
      and one year later in both groups. RESULTS: Women in the intervention group
      showed a decrease in low density lipoprotein (P=.034), (-5.89+/-29.8; 95% CI: 
      13.1/0.27) and an increase in high density lipoprotein (P=.013), (2.71+/-10.6;
      95% CI: -1.36/6.20), as well as improvements in systolic blood pressure (P=.016),
      (-2.16+/-11.8; 95% CI: -4.4/0.01) and frequency (P=.003), (-1.46+/-10.3; 95% CI: 
      3.34/0.42) compared to women in the control group. Women in the control group
      significantly increased glucose (P=.04), (4.84+/-15.5; 95% CI: -0.75/31.3) and
      gamma-glutamyltranspeptidase (P=.031), (3.61+/-14.7; 95% CI: 0.87/6.36) levels
      more than those in the experimental group. CONCLUSIONS: An educational
      intervention can be an effective method of reducing the parameters associated
      with an increased likelihood of cardiovascular disease in women at perimenopausal
      age with hypertension, diabetes mellitus and/or dyslipidaemia.

PMID- 28743400
TI  - Primary and transitory trimethylaminuria: A report of 2 cases.

PMID- 28743401
TI  - Concordance among venous thromboembolism risk assessment models.
AB  - BACKGROUND AND OBJECTIVES: There are a lot of venous thromboembolism risk
      assessment models with the aim of predicting the individual risk of venous
      thromboembolism (VTE), although most have not been externally validated. The
      objective of our study was to analyse the concordance among the Padua, PRETEMED,
      IMPROVE and MEDENOX scores. PATIENTS AND METHODS: Observational cohort study with
      602 patients admitted to Medical Services of the Hospital Universitario Santa
      Lucia. Concordance was calculated using the kappa index (KI) between the four
      risk prediction scales and the VTE occurring within 90 days of hospitalisation.
      RESULTS: Patients considered were those with a high risk of VTE, 78%, 56%, 69%
      and 59% according to Padua, PRETEMED, IMPROVE and MEDENOX scores respectively. A
      KI=0.60 was observed among Padua-IMPROVE scores; KI=0.44 among IMPROVE-PRETEMED,
      KI=0.43 among PRETEMED-MEDENOX, KI=0.33 among Padua-PRETEMED, KI=0.27 among
      IMPROVE-MEDENOX and a KI=0.24 among Padua-MEDENOX. During follow-up, nine cases
      of VTE (1.5%) were observed. CONCLUSIONS: The highest degree of agreement was
      observed among the Padua and IMPROVE scores. There is no good agreement between
      any of the predictive risk scales for VTE in medical patients. The Padua score
      was the best predictor of VTE episodes at 90 days among high risk patients.

PMID- 28743402
TI  - Anaemia in the elderly.
AB  - Anaemia is common in the elderly and is associated with an increased risk of
      physical, functional, and cognitive impairment, hospitalisation and mortality.
      Although it is unknown whether anaemia is a causal factor or a subrogated marker
      of worse health status, its correction can improve the patients' physical and
      functional capacity. Detection, classification, and treatment of anaemia should
      be a priority for the health system. The main causes of anaemia in the elderly
      are nutritional deficiencies and chronic disease, with or without kidney failure,
      although some cases are of indeterminate origin. Medical history and physical
      examination help to clarify its aetiology. A diagnostic algorithm based on data
      from the lab allows anaemia classification with a therapeutic orientation.
      Supplements of iron and maturation factors, as well as erythropoiesis-stimulating
      agents, constitute the mainstay of treatment, along with that of the underlying
      disease, whereas red blood cell transfusion should be reserved for severe cases.

PMID- 28743403
TI  - Obesity-hypoventilation syndrome and associated factors.
AB  - BACKGROUND AND OBJECTIVES: Obesity causes important alterations in the
      respiratory physiology like sleep obstructive apnoea (SOA) and obesity
      hypoventilation syndrome (OHS), both associated with high morbidity and
      mortality. Also, these entities are clearly infradiagnosed and in the case of OHS
      the prevalence is unknown in the general obese population. To determine the
      prevalence of OHS in the population of patients with morbid obesity and to know
      the comorbidity related with OHS, the associated respiratory symptoms and the
      pulse oximetry alterations. PATIENTS AND METHOD: Descriptive study. Selection of
      136 adult patients with morbid obesity (BMI >40). Collected were, anthropometric
      data, toxic habits, concomitant disease, symptom data, analytic data, dyspnoea
      grade, sleepiness scale (Epworth Test), electrocardiogram, chest X-ray,
      spirometry, nocturne ambulatory pulse oximetry and arterial gasometry. RESULTS:
      136 were studied, mean age 60 years old (SD 12.9 years), 73% (98) were women;
      6.6% of patients presented diurnal hypercapnia indicative of OHS; 72% presented
      high blood pressure, 44% dyslipidaemia, 18% presented cardiovascular disease, 83%
      snored and 46% had apnoea; 30% presented stageII dyspnoea and 10% stageIII. The
      desaturation/hour index was above 3% >=30 of occasions in 28.6% of patients and
      the percentage of patients with saturations <90% more than 30% of the time was
      23.5%. The results were worse in patients with OHS. CONCLUSIONS: The prevalence
      of OHS was lower than expected. Noteworthy was the high comorbidity of
      cardiovascular disease and the high frequency of respiratory symptoms associated
      with important alterations of pulse oximetry.

PMID- 28743404
TI  - Bridge therapy in patients under anticoagulation: Is it still the question?

PMID- 28743405
TI  - Miliary tuberculosis during adalimumab therapy in Crohn's disease.

PMID- 28743406
TI  - [Variability in the use of health services by the elderly related to the medical
      list to which they belong].

PMID- 28743407
TI  - Prevalence of undiagnosed uterine leiomyosarcoma in women undergoing hysterectomy
      or myomectomy for benign indications.
AB  - OBJECTIVE: To determine the prevalence of undiagnosed uterine leiomyosarcoma
      (LMS) in women undergoing hysterectomy or myomectomy for suspected benign
      leiomyomas. STUDY DESIGN: Retrospective, single-centre, cohort study. Information
      for all gynaecological procedures for suspected benign leiomyomas between 1993
      and 2016 was extracted from the hospital database. The prevalence of LMS was
      calculated by surgery type and age group. RESULTS: The prevalence of LMS was
      1.7/1000 [one in 603 women; 95% confidence interval (CI) 0.8-3.4] for all
      procedures combined. The prevalence of LMS was 1.1/1000 (one in 875 women; 95% CI
      0.4-2.9) for all hysterectomies combined and 4.2/1000 (one in 240 women; 95% CI
      1.4-12.2) for all myomectomies combined. For women aged <50years, the prevalence
      of LMS was 5.4/1000 (one in 187 women; 95% CI 1.8-15.6) for abdominal
      hysterectomies, 1.0/1000 (one in 1040 women; 95% CI 0.2-5.4) for laparoscopic
      hysterectomies, 5.2/1000 (one in 191 women; 95% CI 0.9-29.1) for abdominal
      myomectomies, 3.0/1000 (one in 332 women; 95% CI 0.5-16.9) for laparoscopic
      myomectomies and 8.6/1000 (one in 116 women; 95% CI 1.5-47.2) for hysteroscopic
      myomectomies. CONCLUSIONS: Occult LMS is a rare malignant disease. This study
      found that the prevalence of LMS was higher in women undergoing myomectomy
      compared with women undergoing hysterectomy. The highest prevalence of LMS was
      found in women undergoing hysteroscopic myomectomy.

PMID- 28743408
TI  - Analysis of concordance between conclusions of forensic psychiatric evaluation
      and court decisions after 2005 Criminal Code Amendment in a Taiwan psychiatric
      hospital.
AB  - The aim of the study is to explore the relationships between results of forensic
      psychiatric evaluation on "mental status at the time of the offense (MSO)" and
      the final decision of the courts after the amendment of the Criminal Code in
      2005. All criminal cases referred to Taipei City Psychiatric Center for MSO
      evaluation from July 1, 2006, to December 31, 2015, were reviewed, and only the
      completed trials were included. Concordance rates in each category of MSO
      conclusion and the court decision were analyzed and compared. The sample
      consisted of 366 MSO evaluations. Overall concordance was 95.6% (350/366). The
      concordance rate in conclusions of "full responsibility", "diminished
      responsibility", and "insanity" were 98.3% (177/180), 97.7% (126/129) and 91.9%
      (34/37) separately, and these three groups showed no statistical significance
      after compared with the other. Conclusions of "intentionally or negligently
      induced insanity or diminished responsibility" reached the lowest concordance at
      65.0% (13/20) and compared with the other three groups all showed statistical
      significance. We found, after the amendment of Criminal Code, the lowest
      concordance rate in those conclusions of "insanity" before change seemed
      diminished. But the conclusions of "intentionally or negligently induced insanity
      or diminished responsibility" became the major origin leading to discordance.
      Comparing to the previous finding in the same hospital which revealed separate
      conclusions resulted in statistically significant concordance rates, the effect
      of the amendment seems likely to improve the consensus among psychiatric experts
      and trial judges except substance and alcohol related mental condition.

PMID- 28743409
TI  - Moral cognition, emotion, and behavior in male youth with varying levels of
      psychopathic traits.

PMID- 28743410
TI  - Low-level laboratory measurement of xenon radionuclides: Electron-photon versus
      photon measurements.
AB  - Radioactive xenon (mainly 131mXe, 133Xe, 133mXe and 135Xe) are tracked as markers
      of nuclear weapons testing. The CEA has developed the PIPSBox, a measurement cell
      able to detect electrons emitted by xenon nuclides. Combined with an ultra-low
      background gamma spectrometer, electron detection capacities allow reaching
      minimum detectable activities (MDA) for a 3-day long measurement of about 0.5mBq
      for the four xenon radionuclides. Compared to a classical measurement cell, MDAs
      are improved by a factor of 2-4.

PMID- 28743411
TI  - Re: Sumanta K. Pal, Guru Sonpavde, Neeraj Agarwal, et al. Evolution of
      Circulating Tumor DNA Profile from First-line to Subsequent Therapy in Metastatic
      Renal Cell Carcinoma. Eur Urol 2017;72:557-64.

PMID- 28743412
TI  - Pseudoexfoliation signs in the anterior segment assessed by optical coherence
      tomography and Scheimpflug device.
AB  - OBJECTIVE: To evaluate different anterior segment parameters in eyes with
      pseudoexfoliation (PSX), fellow eyes, and controls using optical coherence
      tomography and a Scheimpflug imaging system. METHODS: Three groups were studied:
      44 eyes of 44 patients with PSX, 30 clinically unaffected fellow eyes, and 148
      eyes of 148 healthy controls. The anterior chamber depth and volume, corneal
      volume and thickness, pupil diameter and corneal densitometry were measured using
      a Scheimpflug imaging system (Pentacam, Oculus Inc.; Wetzlar, Germany). The angle
      width, the length and area of the trabecular meshwork, and the iris thickness
      were measured using an optical coherence tomography RTVue 100 device (Optovue,
      Fremont, CA, USA). The presence of PSX deposits was also assessed by OCT.
      RESULTS: There were no differences in the anterior chamber volume or depth in the
      corneal volume or central thickness (P>=.228). The corneal densitometry was
      similar between PSX and fellow eyes; however it was greater than in the control
      group (P<.001). As regards the parameters measured by OCT, there were no
      differences in the angle width or in the trabecular meshwork size between the 3
      groups; however, the iris was thinner in controls (P=.005). In all patients the
      PSX deposits were correctly visualised by OCT after the identification by
      biomicroscopy. CONCLUSIONS: There were no differences in the anterior segment
      biometric measurements between patients with PSX and controls, although the
      corneal densitometry and iris thickness were greater in the PSX and fellow eyes
      groups.

PMID- 28743413
TI  - Corneal melting after cataract surgery in a patient with autoimmune disease.
AB  - CASE REPORT: A 78-year-old woman with rheumatoid arthritis and secondary
      Sjogren's syndrome presented with corneal melting three days after cataract
      extraction that required penetrating keratoplasty. By the fourth month, a second
      corneal transplant was needed due to a new descemetocele associated with her
      systemic disease. DISCUSSION: The underlying disease, together with the surgical
      history, was responsible for the complication presented. The correct anamnesis
      prior to cataract surgery, a refined technique, and a close post-operative follow
      up can avoid such a serious complication. Immunomodulatory treatments are
      essential in this type of patient.

PMID- 28743414
TI  - Strabismus-associated myopia. Review.
AB  - INTRODUCTION: The treatment of strabismus associated with myopia is often a
      therapeutic challenge for the ophthalmologist. The strabismus associated with
      myopia has certain peculiarities and there are even certain types of strabismus
      that occur exclusively in myopia, such as strabismus fixus, requiring treatments
      with specific surgical techniques. MATERIALS AND METHODS: It is important to make
      a correct differential diagnosis, because there are many conditions described
      with this association. A review is presented of strabismus associated with
      myopia, together with its treatment adjusted to refractive error. RESULTS:
      Measurements of strabismus may be altered by the prismatic effect of the
      spectacles. Surgical results may be unpredictable if myopia is not taken into
      account. Better results were obtained with the techniques of anatomical
      replacement described by Yokoyama than with traditional retro-insertion
      resection. CONCLUSION: For the diagnosis and appropriate treatment of strabismus,
      it is important to make a correct measurement of the angle of deviation, and
      perform image tests prior to surgery in certain cases. The anatomical
      characteristics of the myopic eye should also be taken into account during
      surgery.

PMID- 28743415
TI  - Colour vision abnormality as the only manifestation of normal pressure
      hydrocephalus.
AB  - CLINICAL CASE: The case is presented of a 73-year-old male patient who referred
      to having black and white vision. Computed tomography showed normal pressure
      hydrocephalus (NPH). Magnetic resonance imaging was not performed because the
      patient refused to undergo further examinations. DISCUSSION: Achromatopsia may be
      the first or only NPH symptom. It may be prudent to ask patients with NPH
      regarding colour vision.

PMID- 28743416
TI  - Asymptomatic choroidal tubercle in a patient with Crohn's disease on adalimumab
      treatment.
AB  - INTRODUCTION: Adalimumab, an anti-tumour necrosis factor alpha therapy for active
      Crohn's disease (CD), is associated with increased risks of tuberculosis
      infection. CASE REPORT: The case is presented of a 48 year-old male with active
      CD on treatment with adalimumab. After three months, he developed a miliary
      pulmonary tuberculosis infection, with a solitary non-reactive choroidal tubercle
      temporal-superior to the optic disc being found in an ophthalmological study.
      Fluorescein angiography showed late hyperfluorescence in a staining pattern.
      Optic coherence tomography showed a flat mass without serous retinal detachment.
      The choroidal tubercle slowly regressed with antituberculosis therapy.
      DISCUSSION: Choroidal tubercles with no vitreo-retinal symptomatology can be
      present in patients with CD and on treatment with adalimumab.

PMID- 28743417
TI  - Determination of acceptance criteria and sample sizes for accelerated stability
      comparability studies for biologics.
AB  - Changes of manufacturing processes are common. It is required by the regulatory
      agencies that manufacturers establish adequate and appropriate comparability
      between pre-change and post-change products. The goals of comparability
      assessments are to demonstrate the comparability and consistency of product
      quality before and after change and to demonstrate that the changes do not have
      an adverse effect on safety and efficacy of the drug products. Accelerated or
      stressed stability studies may shed light on drug quality under stressed
      environmental conditions and on product differences in the degradation pathways.
      Comparability of accelerated stability data may provide further evidence on the
      impact of process change. Equivalence test has been recommended to demonstrate
      the comparability of stability profiles for accelerated stability studies.
      Selection of appropriate acceptance criteria for determining comparability is one
      of the most challenging steps in the comparability studies. Because of the
      inherent heterogeneity of biologics, the stability profiles may vary considerably
      from batch to batch. It is more challenging to set the acceptance criteria for
      comparing the accelerated stability data for biologics. In this article, we
      present an approach for determining the acceptance criteria and necessary sample
      sizes for accelerated comparability studies for biologics.

PMID- 28743418
TI  - Involvement of intestinal efflux and metabolic instability in the
      pharmacokinetics of platycodin D in rats.
AB  - We aimed to investigate the underlying mechanisms for low bioavailability of
      Platycodin D (PD) in rats. The bioavailability of PD was 1.89% with different
      half-lives depending on the administration route (2.14 +/- 0.18 h for intravenous
      injection vs 5.42 +/- 1.9 h for oral administration). The mean absorption time
      was 6.3 h calculated from the mean residence time of both administration routes.
      Consistent with these parameters, rat intestinal permeability using 3 different
      intestinal segments showed a low but greatest permeability in lower ileum (0.05 *
      10-6 cm/s in jejunum and upper ileum vs 0.13 * 10-6 cm/s in lower ileum). The
      involvement of efflux system, probably Mrps, in upper ileum, could be explained
      from the efflux ratio of 6.4 and reduced efflux ratio by an Mrp inhibitor, MK571.
      The recovery of unchanged PD after the intravenous and oral administration was
      50% and 5.2%, respectively, suggesting the contribution of gastrointestinal
      metabolism. In the gastrointestinal content, 4 metabolites of PD were identified:
      acetylated PD (m/z 1265.6), deglucose PD (m/z 1061.5), deapiose PD (m/z 1091.5),
      and deapiose-dexylose-derhamnose PD (m/z 813.4). In conclusion, the intestinal
      first-pass effect such as the presence of efflux functions in the upper ileum,
      limited but steady intestinal permeability, and gastrointestinal metabolism could
      explain the low bioavailability and prolonged absorption time of orally
      administered PD.

PMID- 28743419
TI  - Letter to the Editor.

PMID- 28743420
TI  - Presence of Even a Small Ground-Glass Component in Lung Adenocarcinoma Predicts
      Better Survival.
AB  - BACKGROUND: While lepidic-predominant lung adenocarcinomas are known to have
      better outcomes than similarly sized solid tumors, the impact of smaller
      noninvasive foci within predominantly solid tumors is less clearly characterized.
      We tested the hypothesis that lung adenocarcinomas with even a small ground-glass
      opacity (GGO) component have a better prognosis than otherwise similar pure solid
      (PS) adenocarcinomas. PATIENTS AND METHODS: The maximum total and solid-component
      diameters were determined by preoperative computed tomography in patients who
      underwent lobar or sublobar resection of clinical N0 adenocarcinomas without
      induction therapy between May 2003 and August 2013. Survival between patients
      with PS tumors (0% GGO) or tumors with a minor ground-glass (MGG) component (1%
      25% GGO) was compared by Kaplan-Meier and Cox analyses. RESULTS: A total of 123
      patients met the inclusion criteria, comprising 54 PS (44%) and 69 MGG (56%)
      whose mean ground-glass component was 18 +/- 7%. The solid component tumor
      diameter was not significantly different between the groups (2.3 +/- 1.2 cm vs.
      2.5 +/- 1.3 cm, P = .2). Upstaging to pN1-2 was more common for the PS group (13%
      [7/54] vs. 3% [2/69], P = .04), but the distribution of pathologic stage was not
      significantly different between the groups (PS 76% stage I [41/54] vs. MGG 80%
      stage I [55/69], P = .1). Having a MGG component was associated with markedly
      better survival in both univariate analysis (MGG 5-year overall survival 86.7%
      vs. PS 64.5%, P = .001) and multivariable survival analysis (hazard ratio, 0.30,
      P = .01). CONCLUSION: Patients with resected cN0 lung adenocarcinoma who have
      even a small GGO component have markedly better survival than patients with PS
      tumors, which may have implications for both treatment and surveillance
      strategies.

PMID- 28743421
TI  - A Review of Regimens Combining Pemetrexed With an Epidermal Growth Factor
      Receptor Tyrosine Kinase Inhibitor in the Treatment of Advanced Nonsquamous Non
      Small-Cell Lung Cancer.
AB  - Pemetrexed is a standard first-line treatment for advanced nonsquamous non-small
      cell lung cancer (NSCLC), and epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors (TKIs) are a standard first-line treatment for advanced
      nonsquamous NSCLC with activating EGFR mutations. Pemetrexed and EGFR TKIs have
      different mechanisms of action and minimally overlapping toxicity profiles;
      therefore, it is hypothesized that their combination might result in acceptable
      toxicity, provided that the synergistic antitumor activity observed in
      preclinical studies is achieved. This review summarizes clinical trials of
      pemetrexed in combination with an EGFR TKI for the treatment of advanced
      nonsquamous NSCLC in the first- and second-line settings, using intercalated,
      sequential, and concurrent treatment strategies. As would be expected, such
      strategies were most efficacious in patients with the activating EGFR mutations
      associated with response to an EGFR TKI. In the studies that compared a
      pemetrexed-EGFR TKI combination with pemetrexed alone or the EGFR TKI alone, the
      pemetrexed-EGFR TKI combination was more efficacious than the single-agent
      regimens. The pemetrexed-EGFR TKI combinations were generally associated with a
      higher incidence of grade 3/4 treatment-related adverse events than the single
      agent regimens; however, such toxicities were clinically manageable. Future
      studies of pemetrexed-EGFR TKI combinations should focus on optimizing treatment
      strategies in patients with activating EGFR mutations.

PMID- 28743422
TI  - Editorial.

PMID- 28743423
TI  - Utility of minor determinants for skin testing in inpatient penicillin allergy
      evaluation.
AB  - BACKGROUND: Most patients with a history of penicillin allergy can tolerate
      penicillin. Skin testing can identify tolerant patients, but not all known
      allergenic determinants are commercially available. Protocols exist that use only
      available reagents, but the sensitivity and safety of these protocols,
      particularly for hospitalized patients, are controversial. OBJECTIVE: To
      determine the number of hospitalized patients referred for penicillin skin
      testing who showed unique positivity to the minor determinants penicilloate and
      penilloate. METHODS: A retrospective chart review was conducted of all inpatients
      who underwent penicillin skin testing at 1 institution. Patients were referred by
      their treating physician. All patients underwent skin prick testing to
      benzylpenicilloyl polylysine (major determinant), penicillin G, penicilloate,
      penilloate (minor determinants), amoxicillin, and positive and negative controls.
      If the result was negative, then intradermal testing was done with the same
      penicillin determinants and the negative control. A 4-mm wheal with flare was
      considered a positive reaction. RESULTS: Inpatient penicillin skin testing was
      done in 528 subjects. Any positive test reaction was found in 107 subjects (20%).
      Three subjects (3%) reacted to penilloate only, 25 (23%) reacted to penicilloate
      only, 2 (2%) reacted to penicillin G only, and 8 (8%) reacted to amoxicillin
      only. Sixty-eight subjects (64%) reacted to a compound other than the major
      determinant. CONCLUSION: This study found a high rate of exclusively positive
      skin test reactions to the minor determinants penicilloate and penilloate.
      Because patients with positive test reactions are at increased risk of reaction
      to drug challenge, these data support the use of these reagents for penicillin
      skin testing in hospitalized patients.

PMID- 28743424
TI  - Blood eosinophil-to-basophil ratio in patients with sinonasal polyps: Does it
      have a clinical role?
AB  - BACKGROUND: In a recent preliminary study, eosinophil and basophil counts were
      calculated in chronic rhinosinusitis with nasal polyps (CRSwNP) using
      conventional histologic and immunohistochemical methods. The tissue eosinophil-to
      basophil ratio differed in the CRSwNP endotypes considered. OBJECTIVE: To compare
      the blood eosinophil-to-basophil ratio (bEBR) in a large series of patients with
      CRSwNP with that in a control group of consecutive rhinological patients with no
      evidence of nasal, paranasal, or systemic inflammatory disorders. METHODS: A
      retrospective study was performed on 334 patients with CRSwNP to compare the
      preoperative bEBR among different endotypes and with controls (69 cases).
      RESULTS: The mean bEBR was significantly higher in the CRSwNP group than in the
      control group (P = .0006). The eosinophil and basophil counts were significantly
      and directly correlated in the CRSwNP cases (P = .0000). The mean bEBR was
      significantly higher in the sub-cohorts of CRSwNP with allergy (P = .0007),
      asthma (P = .0000), and aspirin-exacerbated respiratory disease (P = .0153). The
      mean bEBR was significantly higher in the sub-cohort with eosinophilic CRSwNP
      than in the sub-cohort with noneosinophilic CRSwNP (P = .0000). CONCLUSION: This
      study confirms the increasingly interesting role emerging for blood eosinophils
      and basophils in different CRSwNP endotypes. The bEBR seems to be a parameter
      worth investigating in different CRSwNP endotypes, because it is significantly
      higher in patients with allergy, asthma, and aspirin-exacerbated respiratory
      disease.

PMID- 28743425
TI  - Identifying the relationship between beliefs and medication adherence in asthma.

PMID- 28743426
TI  - Sesame allergy in adults: Investigation and outcomes of oral food challenges.

PMID- 28743427
TI  - Contrast-enhancement influences skeletal muscle density, but not skeletal muscle
      mass, measurements on computed tomography.
AB  - BACKGROUND & AIMS: Low skeletal muscle mass and density have recently been
      discovered as prognostic and predictive parameters to guide interventions in
      various populations, including cancer patients. The gold standard for body
      composition analysis in cancer patients is computed tomography (CT). To date, the
      effect of contrast-enhancement on muscle composition measurements has not been
      established. The aim of this study was to determine the effect of contrast
      enhancement on skeletal muscle mass and density measurements on four-phase CT
      studies. DESIGN: In this observational study, two observers measured cross
      sectional skeletal muscle area corrected for patients' height (skeletal muscle
      index [SMI]) and density (SMD) at the level of the third lumbar vertebra on 50
      randomly selected CT examinations with unenhanced, arterial, and portal-venous
      phases. The levels of agreement between enhancement phases for SMI and SMD were
      calculated using intra-class correlation coefficients (ICCs). RESULTS: Mean SMI
      was 42.5 (+/-9.9) cm2/m2 on the unenhanced phase, compared with 42.8 (+/-9.9) and
      43.6 (+/-9.9) cm2/m2 for the arterial and portal-venous phase, respectively (both
      p < 0.01). Mean SMD was lower for the unenhanced phase (30.9 +/- 8.0 Hounsfield
      units [HU]) compared with the arterial (38.0 +/- 9.9 HU) and portal-venous (38.7
      +/- 9.2 HU) phase (both p < 0.001). No significant difference was found between
      SMD in the portal-venous and arterial phase (p = 0.161). The ICCs were excellent
      (>=0.992) for all SMIs and for SMD between the contrast-enhanced phases (0.949).
      The ICCs for the unenhanced phase compared with the arterial (0.676) and portal
      venous (0.665) phase were considered fair to good. CONCLUSIONS: Statistically
      significant differences in SMI were observed between different enhancement
      phases. However, further work is needed to assess the clinical relevance of these
      small differences. Contrast-enhancement strongly influenced SMD values. Studies
      using this measure should therefore use the portal-venous phase of contrast
      enhanced CT examinations.

PMID- 28743428
TI  - A therapeutic benefit of daptomycin against glycopeptide-resistant gram-positive
      cocci bloodstream infections under neutropenia.
AB  - Antibiotic-resistant infections remain to be a major issue for all over the
      world. Although appropriate diagnosis and rapid treatment initiation are
      crucially important particularly in immunocompromised patients, selection of
      antibiotics without identification of causative bacteria is often challenging. A
      44-year-old woman with acute myeloid leukemia (AML) under myelosuppression
      suffered from teicoplanin-resistant gram-positive cocci bacteremia. Taking severe
      neutropenia due to chemotherapy and glycopeptide-resistance into account,
      teicoplanin was empirically substituted with daptomycin, which led to prompt
      defervescence. This microorganism later turned out to be Leuconostoc lactis (L.
      Lactis), and daptmycin was continued to use based on antimicrobial susceptibility
      tests. As a result, empiric use of daptomycin successfully controlled
      glycopeptide-resistant gram-positive cocci bacteremia under neutropenia. This is
      the first report of daptomycin treatment for L. lactis bacteremia in a patient
      with AML under neutropenia. Our findings suggest that daptomycin would be a
      suitable treatment option for glycopeptide-resistant gram-positive cocci
      bloodstream infections, especially in myelosuppressive patients.

PMID- 28743429
TI  - Precision Medicine in Myeloma: Challenges in Defining an Actionable Approach.
AB  - Recently, large sequencing studies have provided insights into the mutational
      landscape of multiple myeloma (MM), identifying actionable mutations and giving a
      precious opportunity for exploring new targeted therapies. The main goal of
      precision medicine, matching patients with the right drug, seems to be closer
      than ever. However, no targeted therapies in MM are approved yet. Several
      clinical trials testing targeted drugs and enrolling patients with MM are
      currently ongoing and will provide predictive biomarkers that might support
      clinical decision making. In this review, we evaluate the evidence supporting the
      implementation of precision medicine in MM and we discuss the challenges that
      should be dealt with in this imminent and promising new era.

PMID- 28743430
TI  - Evaluation of the Root Canal Anatomy of Maxillary and Mandibular Premolars in a
      Selected German Population Using Cone-beam Computed Tomographic Data.
AB  - INTRODUCTION: The aim of this study was to investigate the number of roots and
      the morphology of the root canals of maxillary and mandibular premolars in a
      selected German population. METHODS: Randomly selected full-size cone-beam
      computed tomographic images were collected from 700 patients (45% men and 55%
      women, average age = 50.21 years). This resulted in a total of 644 first and 512
      second maxillary premolars as well as 1044 first and 871 second mandibular
      premolars. The total number of roots and root canals, the frequency and
      correlations between the left and right sides, and the incidence in men and women
      were recorded and statistically analyzed using the Fisher exact and chi-square
      tests. Canal configurations were classified according to the Vertucci
      classification. RESULTS: First maxillary premolars mainly had 2 roots (1 root:
      36.4%, 2 roots: 62.4%, and 3 roots: 1.2%) with predominantly 2 canals (88.4%).
      The majority of second maxillary premolars had 1 root (82.6%), but 2 root canals
      (56.3%) occurred more frequently than 1 canal (43.1%). In the first and second
      mandibular premolars, 1 root was found predominantly (90.76% and 98.16%,
      respectively) with 1 canal (77.9% and 96.0%), whereas 2 canals were less common
      (21.9% and 3.6%). Three roots (0%, <0.11%) and 3 canals (0.2%; 0.4%) were rarely
      found. Vertucci classifications were heterogeneously distributed. Men showed
      significantly more roots and root canals compared with women (P < .05), with the
      exception of the second mandibular premolars. CONCLUSIONS: This cone-beam
      computed tomographic study confirmed previous anatomic and morphologic
      investigations. When treating premolars, the likelihood of additional root canals
      should be considered.

PMID- 28743431
TI  - Regenerative Endodontic Therapy in the Management of Nonvital Immature Permanent
      Teeth: A Systematic Review-Outcome Evaluation and Meta-analysis.
AB  - INTRODUCTION: Although the protocols in previously published studies appeared to
      be largely similar, there were inadequate evidence-based guidelines to support a
      single protocol. Using a meta-analysis, this systematic review aimed to summarize
      and quantitatively evaluate the outcomes for nonvital immature permanent teeth
      treated using the regenerative endodontic technique (RET) as well as critically
      appraise the level and quality of evidence of the existing publications. METHODS:
      Risk of bias assessment and level of evidence grading were performed on all
      included studies. Meta-analyses using a random effects model were performed to
      combine the results of randomized controlled trials. The pooled success rate for
      each exposure was estimated for each outcome (event rates with 95% confidence
      intervals). The outcomes of all included studies were summarized. RESULTS:
      Success rates for tooth survival and resolution of periapical pathosis were
      excellent; however, results for apical closure and continued root development
      were inconsistent. There are few well-reported randomized prospective clinical
      studies. Reporting of long-term outcomes and late-stage effects was sparse. No
      study evaluated health economic outcomes and improvements to patients' quality of
      life. CONCLUSIONS: Many knowledge gaps still exist within the studies published.
      Current published evidence is unable to provide definitive conclusions on the
      predictability of RET outcomes.

PMID- 28743432
TI  - High levels of eukaryotic Initiation Factor 6 (eIF6) are required for immune
      system homeostasis and for steering the glycolytic flux of TCR-stimulated CD4+ T
      cells in both mice and humans.
AB  - Eukaryotic Initiation Factor 6 (eIF6) is required for 60S ribosomal subunit
      biogenesis and efficient initiation of translation. Intriguingly, in both mice
      and humans, endogenous levels of eIF6 are detrimental as they act as tumor and
      obesity facilitators, raising the question on the evolutionary pressure that
      maintains high eIF6 levels. Here we show that, in mice and humans, high levels of
      eIF6 are required for proper immune functions. First, eIF6 heterozygous (het)
      mice show an increased mortality during viral infection and a reduction of
      peripheral blood CD4+ Effector Memory T cells. In human CD4+ T cells, eIF6 levels
      rapidly increase upon T-cell receptor activation and drive the glycolytic switch
      and the acquisition of effector functions. Importantly, in CD4+ T cells, eIF6
      levels control interferon-gamma (IFN-gamma) secretion without affecting
      proliferation. In conclusion, the immune system has a high evolutionary pressure
      for the maintenance of a dynamic and powerful regulation of the translational
      machinery.

PMID- 28743433
TI  - Scavengers for bacteria: Rainbow trout have two functional variants of MARCO that
      bind to gram-negative and -positive bacteria.
AB  - Class A scavenger receptors (SR-As) are a family of surface-expressed receptors
      who bind a wide range of polyanionic ligands including bacterial components and
      nucleic acids and play a role in innate immunity. Macrophage receptor with
      collagenous structure (MARCO) is a SR-A family member that has been studied in
      mammals largely for its role in binding bacteria. To date there is little
      information about SR-As in general and MARCO specifically in fish, particularly
      what ligands individual SR-A family members bind remains largely unknown. In the
      present study two novel rainbow trout MARCO transcript variants have been
      identified and their sequence and putative protein domains have been analyzed.
      When overexpressed in CHSE-214, a cell line that appears to lack functional
      scavenger receptors, GFP-tagged rtMARCO-1 and rtMARCO-2 were able to bind gram
      positive, and gram-negative bacteria of both mammalian and aquatic sources.
      rtMARCO appears to bind bacteria via its scavenger receptor cysteine-rich (SRCR)
      domain, because SRCR deleted rtMARCO-1 and -2 were unable to bind bacteria.
      rtMARCO did not show any binding to the yeast cell wall component zymosan or to
      double-stranded (ds)RNA. This is the first time rainbow trout MARCO sequences
      have been identified and the first in-depth study exploring their ligand binding
      profile. This study provides novel insight into the role of rainbow trout MARCO
      in bacterial innate immunity.

PMID- 28743434
TI  - Editorial overview: Virus structure and functions.

PMID- 28743435
TI  - Editorial overview: Antiviral strategies: Antiviral drug design: creating new
      ideas against old and new bugs.

PMID- 28743436
TI  - Validation of a Brief Questionnaire Against Direct Observation to Assess
      Adolescents' School Lunchtime Beverage Consumption.
AB  - OBJECTIVE: Beverage consumption is an important determinant of youth health
      outcomes. Beverage interventions often occur in schools, yet no brief validated
      questionnaires exist to assess whether these efforts improve in-school beverage
      consumption. This study validated a brief questionnaire to assess beverage
      consumption during school lunch. METHODS: Researchers observed middle school
      students' (n = 25) beverage consumption during school lunchtime using a
      standardized tool. After lunch, students completed questionnaires regarding their
      lunchtime beverage consumption. Kappa statistics compared self-reported with
      observed beverage consumption across 15 beverage categories. RESULTS: Eight
      beverages showed at least fair agreement (kappa [kappa] > 0.20) for both type and
      amount consumed, with most showing substantial agreement (kappa > 0.60). One
      beverage had high raw agreement but kappa < 0.20. Six beverages had too few
      ratings to compute kappa's. CONCLUSIONS AND IMPLICATIONS: This brief
      questionnaire was useful for assessing school lunchtime consumption of many
      beverages and provides a low-cost tool for evaluating school-based beverage
      interventions.

PMID- 28743437
TI  - College Cafeteria Signage Increases Water Intake but Water Position on the Soda
      Dispenser Encourages More Soda Consumption.
AB  - OBJECTIVES: To evaluate the effects of improved water location visibility and
      water dispenser position on the soda dispenser on undergraduate students'
      beverage choices. METHODS: Two focus groups with pilot intervention surveys
      before and after, adding a small sign above the soda dispensers' water button for
      6 weeks in a large US university's all-you-can-eat, prepaid dining hall (measured
      with chi-square tests and logistic and ordinal logistic regression). RESULTS:
      Focus groups included 15 students. Survey participants included 357 students
      before and 301 after the intervention. After the intervention, more students
      reported ever having drunk water with the meal (66.4% to 77.0%; P = .003) and
      water consumption frequency increased (P = .005). Postintervention, the odds of
      drinking water increased by 1.57. Preference for other drinks was the main reason
      for not drinking water. A total of 59% of students had ever changed their
      preference from water to soda. CONCLUSIONS AND IMPLICATIONS: The clear indication
      of the water's location increased students' reported water consumption. Further
      investigation is needed into how a non-independent water dispenser influences
      students' beverage choice. Clearly labeled, independent water dispensers are
      recommended.

PMID- 28743438
TI  - Fruit and Vegetable Preferences and Identification by Kindergarteners through 2nd
      Graders With or Without the US Department of Agriculture Fresh Fruit and
      Vegetable Program.
AB  - OBJECTIVE: The US Department of Agriculture Fresh Fruit and Vegetable Program
      (FFVP) allows schools to increase fruit and vegetable (FV) exposure by
      distributing FV as snacks. The objective of this study was to compare
      kindergarten through second (K-2nd)-graders who were exposed or not to FFVP for
      preferences and identification. DESIGN, SETTING, PARTICIPANTS: The FV Preference
      Survey for K-2nd-graders contained 12 fruits and 12 vegetables, a 3-Likert scale
      (liked it, okay, don't like it), and an I don't know option. Data were collected
      from K-2nd-graders at 2 elementary schools near Chicago, IL (n = 435, FFVP
      school, n = 235 with 12 teachers; non-FFVP school, n = 200 with 10 teachers).
      MAIN OUTCOME MEASURE(S): Mean preference scores. ANALYSIS: Chi-square, Mann
      Whitney U, and multiple linear regression analyses compared school data (P <
      .05). RESULTS: There were significant differences in mean preference scores, with
      higher fruit scores at the FFVP school (1.8 +/- 0.6) than at the non-FFVP school
      (1.7 +/- 0.6). In contrast, there was a higher vegetable score for the non-FFVP
      school (1.3 +/- 0.9) than for the FFVP school (1.2 +/- 0.9). The school variable
      had weak impact on fruit ranking (multivariate coefficient = 0.01; P < .05). For
      fruits and vegetables and combined, there were fewer I don't know responses in
      the FFVP (chi2 = 149.080; P < .01). CONCLUSIONS AND IMPLICATIONS: At the FFVP
      school, fewer I don't know responses suggested better FV identification. Non-FFVP
      students had higher vegetable preferences than did FFVP students. Tasting a
      variety of FV may help with identifying FV, but more research is needed to
      determine the impact on preferences.

PMID- 28743439
TI  - The Electrocardiographic Footprints of Wenckebach Block.
AB  - In 1899, Karel Frederik Wenckebach described a cardiac arrhythmia with periodic
      dropped beats now referred to as a Wenckebach sequence. This was later shown to
      be due to a block in the atrioventricular node, but today, we identify Wenckebach
      sequences throughout the heart with most being recognised on the surface
      electrocardiograph as characteristic footprints. This manuscript will revisit
      Wenckebach atrioventricular block, the typical features of which only occur in
      about 15% of cases, with the remainder atypical. Earlier reports regarded
      Wenckebach atrioventricular sequences as rare as they are only occasionally seen
      on the surface 12-lead electrocardiograph. Today, however, with the increased use
      of ambulatory Holter monitoring, Wenckebach atrioventricular sequences occur in 4
      6% of all traces and are particularly common at night in the young. Most, but not
      all cases are benign and the clinical spectrum will be reviewed. Atypical
      Wenckebach atrioventricular sequences are a complex group which will be analysed
      in detail with a broad range of illustrations. Outside the atrioventricular
      conducting system, such as in the sinus node, Wenckebach sequences may not be
      obvious as they are partially hidden from the electrocardiographic tracing.
      However, by understanding the sequence footprints, clues are available in
      interpreting tracing with periodic pauses. Dual chamber paced rhythms may show
      Wenckebach sequences due to electronic control of the atrioventricular delay.
      Rarely exit blocks at the cellular level in the atrium, ventricle or at the
      pacing electrode-tissue interface can demonstrate Wenckebach sequences recognised
      on the surface electrocardiograph.

PMID- 28743440
TI  - The use of intrapartum ultrasound to diagnose malpositions and cephalic
      malpresentations.
AB  - Fetal malpositions and cephalic malpresentations are well-recognized causes of
      failure to progress in labor. They frequently require operative delivery, and are
      associated with an increased probability of fetal and maternal complications.
      Traditional obstetrics emphasizes the role of digital examinations, but recent
      studies demonstrated that this approach is inaccurate and intrapartum ultrasound
      is far more precise. The objective of this review is to summarize the current
      body of literature and provide recommendations to identify malpositions and
      cephalic malpresentations with ultrasound. We propose a systematic approach
      consisting of a combination of transabdominal and transperineal scans and
      describe the findings that allow an accurate diagnosis of normal and abnormal
      position, flexion, and synclitism of the fetal head. The management of
      malpositions and cephalic malpresentation is currently a matter of debate, and
      individualized depending on the general clinical picture and expertise of the
      provider. Intrapartum sonography allows a precise diagnosis and therefore offers
      the best opportunity to design prospective studies with the aim of establishing
      evidence-based treatment. The article is accompanied by a video that demonstrates
      the sonographic technique and findings.

PMID- 28743441
TI  - Quality of life of menopausal women with genital urinary menopause syndrome.

PMID- 28743442
TI  - Reply.

PMID- 28743443
TI  - A vicious cycle of causes and consequences of dyspareunia: rethinking the
      approach to management of genitourinary syndrome of menopause.

PMID- 28743444
TI  - The value of the cerebroplacental ratio in appropriate-for-gestational-age
      fetuses.

PMID- 28743445
TI  - Recap-Minimally invasive treatment for cesarean scar pregnancy using a double
      balloon catheter: additional suggestions to the technique.

PMID- 28743446
TI  - Measuring the impact of attending physician teaching in an obstetrics and
      gynecology residency program.

PMID- 28743447
TI  - Dual-targeted anti-TB/anti-HIV heterodimers.
AB  - HIV and M. tuberculosis are two intersecting epidemics making the search for new
      dual action drugs against both pathogens extremely important. Here, we report on
      the synthesis and suppressive activities of five dual-targeted HIV/TB compounds.
      These compounds are heterodimers of AZT, as anti-HIV molecules, and 5-substituted
      uracil derivatives, as anti-TB molecules. We found that these compounds inhibit
      the growth of M. tuberculosis and suppress the replication of HIV in human cell
      cultures and human lymphoid tissues ex vivo. We identified one particular
      heterodimer that inhibited both HIV and the drug-resistant TB strain MS-115 most
      potently. This compound demonstrated low toxicity and had no cytostatic effect on
      cells in culture, constituting an ideal candidate for future development and
      further in vivo testing.

PMID- 28743448
TI  - Chronic CB1 cannabinoid receptor antagonism persistently increases dendritic
      spine densities in brain regions important to zebra finch vocal learning and
      production in an antidepressant-sensitive manner.
AB  - During typical late-postnatal CNS development, net reductions in dendritic spine
      densities are associated with activity-dependent learning. Prior results showed
      agonist exposure in young animals increased spine densities in a subset of song
      regions while adult exposures did not, suggesting endocannabinoid signaling
      regulates dendritic spine dynamics important to vocal development. Here we
      addressed this question using the CB1 receptor-selective antagonist SR141716A
      (SR) to disrupt endocannabinoid signaling both during and after vocal learning.
      We hypothesized antagonist exposure during vocal development, but not adulthood,
      would alter spine densities. Following 25days of exposure and a 25day maturation
      period, 3D reconstructions of Golgi-Cox stained neurons were used to measure
      spine densities. We found antagonist treatments during both age periods increased
      densities within Area X (basal ganglia) and following adult treatments within HVC
      (premotor cortical-like). Results suggest both inappropriate cannabinoid receptor
      stimulation and inhibition are capable of similar disregulatory effects during
      establishment of circuits important to vocal learning, with antagonism extending
      these effects through adulthood. Given clinical evidence of depressant effects of
      SR, we tested the ability of the antidepressant monoamine oxidase inhibitor
      (MAOI) phenelzine to mitigate SR-induced spine density increases. This was
      confirmed implicating interaction between monoamine and endocannabinoid systems.
      Finally, we evaluated acute effects of these drugs to alter ability of novel song
      exposure to increase spine densities in auditory NCM and other regions, finding
      when combined, SR and phenelzine increased densities within Area X. These results
      contribute to understanding relevance of dendritic spine dynamics in neuronal
      development, drug abuse, and depression.

PMID- 28743449
TI  - Dengue serotype circulation in natural populations of Aedes aegypti.
AB  - Ae. aegypti is the main vector of dengue (DENV), Zika (ZIKV), and chikungunya
      (CHIKV) viruses. The transmission dynamics of these arboviruses, especially the
      arboviral circulation in the mosquito population during low and high transmission
      seasons in endemic areas are still poorly understood. We conducted an
      entomological survey to determine dengue infection rates in Ae. aegypti and Aedes
      albopictus. These collections were performed in 2012-2013 during a Rio de Janeiro
      epidemic, just before the introduction and spread of ZIKV and CHIKV in the city.
      MosquiTrap(c) and BG-Sentinel traps were installed in three fixed and seven
      itinerant neighborhoods each month over ten months. Mosquitoes were in
      supernatants pools tested and individually confirmed for DENV infection using RT
      PCR. A total of 3053 Aedes mosquitos were captured and Ae. aegypti was much more
      frequent (92.9%) than Ae. albopictus (6.8%). Ae. aegypti females accounted for
      71.8% of captured mosquitoes by MosquitTrap(c) and were the only species found
      naturally infected with DENV (infection rate=0.81%). Only one Ae. aegypti male,
      collected by BG-sentinel, was also tested positive for DENV. The peak of DENV
      positive mosquitoes coincided the season of the highest incidence of human cases.
      The most common serotypes detected in mosquitoes were DENV-3 (24%) and DENV-1
      (24%), followed by DENV-4 (20%), DENV-2 (8%) and DENV-1 plus DENV4 (4%), while
      95% of laboratory-confirmed human infections in the period were due to DENV-4.
      These contrasting results suggest silent maintenance of DENV serotypes during the
      epidemics, reinforcing the importance of entomological and viral surveillance in
      endemic areas.

PMID- 28743450
TI  - Field evaluation of a semi-automatic funnel trap targeted the medically important
      non-biting flies.
AB  - Bait-trapping is a useful approach for monitoring fly population dynamics, and it
      is an effective tool for physical control of pest species. The aim of this study
      was to test a newly developed semi-automatic funnel fly trap with some
      modifications of the former prototype fly trap to study medically important fly
      population density. The efficacy of the semi-automatic funnel trap was assessed
      by field sampling during July 2013-June 2014 using 1-day tainted beef offal as
      bait. The modified semi-automatic funnel traps were able to capture a total of
      151,141 adult flies, belonging to the families: Calliphoridae (n=147,248; 97.4%),
      Muscidae (n=3,124; 2.1%) and Sarcophagidae (n=769; 0.5%), which are the medically
      important fly species. Among the total of 35 species collected, Chrysomya
      megacephala (Diptera: Calliphoridae) (n=88,273; 59.95%), Musca domestica
      (Diptera: Muscidae) (n=1,324; 42.38%) and Boettcherisca peregrina (Diptera:
      Sarcophagidae) (n=68; 33.01%) were the predominant species of each family. High
      number of flies was captured in forest area, representing 42.47% (n=64,197) of
      total specimens. Female flies were trapped more than male with total sex ratio of
      0.37 male/female. Flies were trapped throughout the year with peak population in
      summer. Peak activity was recorded in the afternoon (12.00-18.00h). In summary,
      the modified semi-automatic funnel fly trap can be used for field collection of
      the adult fly. By setting the timer, population dynamics, diversity, and periodic
      activity of adult flies were determined.

PMID- 28743451
TI  - Genetic diversity of 21 autosomal STR loci in the Han population from Sichuan
      province, Southwest China.
AB  - Exploration of the ethnic origin and genetic differentiation of 56 Chinese
      officially recognized nationalities populations played a fundamental role in the
      research field of population genetics, forensic science, linguistics,
      anthropology, and archaeology. In the present study, population data of 21
      autosomal STR loci (CSF1PO, D10S1248, D12S391, D13S317, D16S539, D18S51, D19S433,
      D21S11, D2S1338, D2S441, D3S1358, D5S818, D6S1043, D7S820, D8S1179, FGA, Penta D,
      Penta E, TH01, TPOX, and vWA) included in the AGCU EX22 kit in 2793 Southwest Han
      Chinese individuals was obtained and population genetic relationships among 28
      Chinese populations were investigated. Our study indicated that the twenty-one
      autosomal STRs are highly polymorphic in the Sichuan Han population and can be
      used as a powerful tool in the routine forensic usage. MDS and phylogenetic
      analysis suggested that the Sichuan Han population kept a close genetic
      relationship with the southwest populations.

PMID- 28743452
TI  - Transcriptional profiles for distinct aggregation states of mutant Huntingtin
      exon 1 protein unmask new Huntington's disease pathways.
AB  - Huntington's disease is caused by polyglutamine (polyQ)-expansion mutations in
      the CAG tandem repeat of the Huntingtin gene. The central feature of Huntington's
      disease pathology is the aggregation of mutant Huntingtin (Htt) protein into
      micrometer-sized inclusion bodies. Soluble mutant Htt states are most proteotoxic
      and trigger an enhanced risk of death whereas inclusions confer different changes
      to cellular health, and may even provide adaptive responses to stress. Yet the
      molecular mechanisms underpinning these changes remain unclear. Using the flow
      cytometry method of pulse-shape analysis (PulSA) to sort neuroblastoma (Neuro2a)
      cells enriched with mutant or wild-type Htt into different aggregation states, we
      clarified which transcriptional signatures were specifically attributable to
      cells before versus after inclusion assembly. Dampened CREB signalling was the
      most striking change overall and invoked specifically by soluble mutant Httex1
      states. Toxicity could be rescued by stimulation of CREB signalling. Other
      biological processes mapped to different changes before and after aggregation
      included NF-kB signalling, autophagy, SUMOylation, transcription regulation by
      histone deacetylases and BRD4, NAD+ biosynthesis, ribosome biogenesis and altered
      HIF-1 signalling. These findings open the path for therapeutic strategies
      targeting key molecular changes invoked prior to, and subsequently to, Httex1
      aggregation.

PMID- 28743453
TI  - Pregnane X Receptor Deletion Modifies Recognition Memory and
      Electroencephalographic Activity.
AB  - Nuclear receptors (NR) are emerging as key players in the central nervous system
      (CNS) with reported implications in physiological and pathophysiological
      conditions. While a number of NR has been studied, it is unknown whether
      invalidation of the pregnane xenobiotic receptor (PXR, NR1I2) corresponds to
      neurological modifications in the adult brain. PXR-/- C57BL/6J and wild-type mice
      were used to investigate: (i) recognition memory, motor coordination, and anxiety
      like behaviors; (ii) longitudinal video-electroencephalographic (EEG) recordings
      and frequency wave analysis; (iii) neurovascular structures by histological
      evaluation and expression of the cerebrovascular tight junctions ZO1 and CLDN5.
      Absence of PXR was associated with anxiety-like behavior and recognition memory
      impairment in adult mice. The latter was simultaneous to an EEG signature of
      lower theta frequency during sleep and abnormal delta waves. Neurophysiological
      changes did not correspond to significant structural changes in the adult brain,
      expect for a localized and minor increase in the fronto-parietal neurovascular
      density and reduced ZO1, but not CLDN5, expression in isolated brain capillaries.
      Our results converge with existing evidence supporting a link between NR
      expression and brain physiology. Although the exact modalities remain to be
      elucidated, the possibility that extra-physiological modulation of PXR may
      constitute a pathophysiological entry point or a molecular target for brain
      diseases is proposed.

PMID- 28743454
TI  - Convergence of primary sensory cortex and cerebellar nuclei pathways in the
      whisker system.
AB  - To safely maneuver through the environment the brain needs to compare active
      sensory information with ongoing motor programs. This process occurs at various
      levels in the brain: at the lower level, i.e., in the spinal cord, reflexes are
      generated for the most primitive motor responses; at the intermediate level,
      i.e., in the brainstem, various nuclei co-process sensory- and motor-related
      inputs; and, at the higher level cerebellum and thalamo-cortical networks
      individually compute suitable commands for fine-tuned motor output. For
      sensorimotor processes the integrative capacities of the cerebral cortex and the
      cerebellum have been the topic of detailed analysis. Here, we use higher order
      sensorimotor integration in the whisker system as a model to evaluate the
      convergence pattern of primary sensory cortex projections and the cerebellar
      output nuclei throughout several brain nuclei. This prospective review focuses
      not only on the thalamus, but also incorporates extra-thalamic structures that
      could function as comparators of cerebellar output and sensory cortex output.
      Based on the literature on anatomical and physiological studies in the rodent
      brain and our qualitative data on the convergence of cerebellar sensory cortical
      projections we identify the superior colliculus as well as the zona incerta and
      the anterior pretectal nucleus as suitable candidates for cerebello-cortical
      convergence. Including these putative comparators we discuss the potential routes
      for sensorimotor information flow between the cerebellum and cerebral sensory
      cortex with a focus on the modulation of thalamic activity by extra-thalamic
      structures.

PMID- 28743455
TI  - Corrigendum to "Time orientation and eating behavior: Unhealthy eaters consider
      immediate consequences, while healthy eaters focus on future health" [Appetite 91
      (2015) 13-19].

PMID- 28743456
TI  - Distraction coping predicts better cortisol recovery after acute psychosocial
      stress.
AB  - The aim of this study was to explore whether different manifestations of state
      coping predict cortisol response and recovery in an acute stress situation. Fifty
      nine healthy adults (59.3% female) were exposed to the Trier Social Stress Test
      (TSST), and salivary cortisol was measured repeatedly before and after stress.
      Hierarchical linear modeling was used to test for relationships between factor
      analytically derived measures of state coping and cortisol response and recovery.
      Independent of sex, age, BMI, chronic stress and depression, denial coping was
      related with higher peak levels of cortisol (beta=0.0798, SE=0.0381, p=0.041)
      while distraction coping predicted steeper recovery after TSST (linear effect:
      beta=-0.0430, SE=0.0184, p=0.023) and less pronounced curvature (quadratic
      effect: beta=0.0043, SE=0.0017, p=0.016). Our results demonstrate the stress
      buffering effect of distraction coping on hypothalamic-pituitary-adrenal (HPA)
      axis activity in situations without sufficient control.

PMID- 28743457
TI  - Mental imagery of face enhances face-sensitive event-related potentials to
      ambiguous visual stimuli.
AB  - Visual mental imagery forms mental representations of visual objects when
      correspondent stimuli are absent and shares some characters with visual
      perception. Both the vertex-positive-potential (VPP) and N170 components of event
      related potentials (ERPs) to visual stimuli have a remarkable preference to
      faces. This study investigated whether visual mental imagery modulates the face
      sensitive VPP and/or N170 components. The results showed that with significantly
      larger amplitudes under the face-imagery condition than the house-imagery
      condition, the VPP and P2 responses, but not the N170 component, were elicited by
      phase-randomized ambiguous stimuli. Thus, the brain substrates underlying VPP are
      not completely identical to those underlying N170, and the VPP/P2 manifestation
      of the category selectivity in imagery probably reflects an integration of top
      down mental imagery signals (from the prefrontal cortex) and bottom-up perception
      signals (from the early visual cortex) in the occipito-temporal cortex where VPP
      and P2 originate.

PMID- 28743458
TI  - S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without
      influencing locomotor activity.
AB  - S-phenylpiracetam is an optical isomer of phenotropil, which is a clinically used
      nootropic drug that improves physical condition and cognition. Recently, it was
      shown that S-phenylpiracetam is a selective dopamine transporter (DAT) inhibitor
      that does not influence norepinephrine (NE) or serotonin (5-HT) receptors. The
      aim of the present study was to study the effects of S-phenylpiracetam treatment
      on body weight gain, blood glucose and leptin levels, and locomotor activity.
      Western diet (WD)-fed mice and obese Zucker rats were treated daily with peroral
      administration of S-phenylpiracetam for 8 and 12weeks, respectively. Weight gain
      and plasma metabolites reflecting glucose metabolism were measured. Locomotor
      activity was detected in an open-field test. S-phenylpiracetam treatment
      significantly decreased body weight gain and fat mass increase in the obese
      Zucker rats and in the WD-fed mice. In addition, S-phenylpiracetam reduced the
      plasma glucose and leptin concentration and lowered hyperglycemia in a glucose
      tolerance test in both the mice and the rats. S-phenylpiracetam did not influence
      locomotor activity in the obese Zucker rats or in the WD-fed mice. The results
      demonstrate that S-phenylpiracetam reduces body weight gain and improves
      adaptation to hyperglycemia without stimulating locomotor activity. Our findings
      suggest that selective DAT inhibitors, such as S-phenylpiracetam, could be
      potentially useful for treating obesity in patients with metabolic syndrome with
      fewer adverse health consequences compared to other anorectic agents.

PMID- 28743459
TI  - Illuminating the conceptual structure of the space of moral violations with
      searchlight representational similarity analysis.
AB  - Characterizing how representations of moral violations are organized, cognitively
      and neurally, is central to understanding how people conceive and judge them.
      Past work has identified brain regions that represent morally relevant features
      and distinguish moral domains, but has not yet advanced a broader account of
      where and on what basis neural representations of moral violations are organized.
      With searchlight representational similarity analysis, we investigate where
      category membership drives similarity in neural patterns during moral judgment of
      violations from two key moral domains: Harm and Purity. Representations converge
      across domains in a network of regions resembling the mentalizing network.
      However, Harm and Purity violation representations respectively converge in
      different regions: precuneus (PC) and left inferior frontal gyrus (LIFG).
      Examining substructure within moral domains, Harm violations converge in PC
      regardless of subdomain (physical harms, psychological harms), while Purity
      subdomains (pathogen-related violations, sex-related violations) converge in
      distinct sets of regions - mirroring a dissociation observed in principal
      component analysis of behavioral data. Further, we find initial evidence for
      representation of morally relevant features within these two domain-encoding
      regions. The present analyses offer a case study for understanding how
      organization within the complex conceptual space of moral violations is reflected
      in the organization of neural patterns across the cortex.

PMID- 28743460
TI  - High-resolution in vivo imaging of human locus coeruleus by magnetization
      transfer MRI at 3T and 7T.
AB  - Locus Coeruleus (LC) is a neuromelanin-rich brainstem structure that is the
      source of noradrenaline in the cortex and is thought to modulate attention and
      memory. LC imaging in vivo is commonly performed with a 2D T1-weighted Turbo Spin
      Echo (TSE) MRI sequence, an approach that suffers from several drawbacks at 3T,
      including long acquisition times and highly anisotropic spatial resolution. In
      this study, we developed a high-resolution Magnetization Transfer (MT) sequence
      for LC imaging at both 7T and 3T and compared its performance to a TSE sequence.
      Results indicate that LC imaging can be achieved with an MT sequence at both 7
      and 3T at higher spatial resolution than the 3T TSE. Furthermore, we investigated
      whether the currently disputed source of contrast in the LC region with a TSE
      sequence relates to MT effects or shortened T1 and T2* due to increased iron
      concentration. Our results suggest that the contrast in the LC area relates to MT
      effects. To conclude, in this study we managed to image the LC, for the first
      time, at 7T and at an increased resolution compared to the current state-of-the
      art. Imaging the LC is highly relevant for clinical diagnostics as structural
      tissue properties of the LC may hold promise as a biomarker in neurodegenerative
      diseases.

PMID- 28743461
TI  - Effects of subchronic exposure to waterborne cadmium on H-P-I axis hormones and
      related genes in rare minnows (Gobiocypris rarus).
AB  - The H (hypothalamic)-P (pituitary)-I (interrenal) axis is critical in the stress
      response and other activities of fish. To further investigate cadmium (Cd)
      toxicity on the H-P-I axis and to identify its potential regulatory genes in
      fish, the adult female rare minnows (Gobiocypris rarus) were exposed to
      subchronic (5weeks) levels of waterborne Cd in the present study. This kind of
      treatment caused dose-dependent decline in fish growth, with significance in the
      high dose group (100MUg/L). Correspondingly, low dose (5-50MUg/L) waterborne Cd
      disrupted the endocrine system of H-P-I axis just at the secretion level, while
      high dose Cd disrupted both the secretion and synthesis of cortisol and its
      downstream signals in rare minnows, revealed by the significantly upregulation
      and positive correlation of corticosteroidogenic genes including MC2R, StAR,
      CYP11A1, and CYP11B1 in the kidney (including the interrenal tissue) (P<0.05),
      and the significant alteration of Glcci1, Hsp90AA and Hsp90AB in the
      hepatopancreas, gill and intestine as well (P<0.05). The expression of Glcci1 was
      significantly decreased in hepatopancreas, gill and intestine of tested fish
      following treatment, and its positive correlation with GR (Glucocorticoid
      receptor) suggested its potential regulation on the cortisol and/or H-P-I axis in
      fish. The expression of FKBP5 in the intestine was positively and significantly
      correlated with that of Hsp90AA (P<0.05), and the Hsp90AB transcript in the
      hepatopancreas was positively correlated with that of Hsp90AA (P<0.05), which
      indicated that Hsp90AA and Hsp90AB were more likely to serve as cofactors of GR
      and FKBP5 in response to Cd exposure.

PMID- 28743462
TI  - Bacteriophages in the human gut: Our fellow travelers throughout life and
      potential biomarkers of heath or disease.
AB  - The gastrointestinal (GI) tract is populated by a huge variety of viruses.
      Bacterial viruses (bacteriophages) constitute the largest and the most
      unrecognized part of virome. The total bacteriophage community of the human gut
      is called phageome. Phages colonize the gut from the earliest moments of life and
      become our fellow travelers throughout life. Phageome seems to be unique to each
      individual and shows a high degree of interpersonal variation. In the healthy
      gut, a vast majority of phages have a lysogenic lifestyle. These prophages serve
      as a major respository of mobile genetic elements in the gut and play key roles
      in the exchange of genetic material between bacterial species via horizontal gene
      transfer (HGT). But, imbalance in the gut microbial community during dysbiosis,
      caused by diseases or environmental stresses such as antibiotics, is accompanied
      by induction of prophages leading to a decreased ratio of symbionts to
      pathobionts. Based on this, a diseased gut is transformed from an environment
      predominantly occupied by prophages to an ecosystem mostly inhabited by lytic
      phages. A growing body of evidence has provided support for the notion that
      phageome structure and composition change dependent on the physiological or
      pathological status of the body. This has been demonstrated by pronounced
      quantitative and qualitative differences between the phageome of healthy
      individuals and patients. Although many aspects of the contribution made by
      phages to human biology remain to be understood, recent findings favor the
      suggestion that phageome might represent potential to serve as a biomarker of
      health or disease.

PMID- 28743463
TI  - Study of RNA-A Initiation Translation of The Infectious Pancreatic Necrosis
      Virus.
AB  - The infectious pancreatic necrosis virus (IPNV) is a salmonid pathogen that
      causes significant economic losses to the aquaculture industry. IPNV is a non
      enveloped virus containing two uncapped and non-polyadenylated double strand RNA
      genomic segments, RNA-A and RNA-B. The viral protein Vpg is covalently attached
      to the 5' end of both segments. There is little knowledge about its viral cycle,
      particularly about the translation of the RNAs. Through experiments using mono
      and bicistronic reporters, in this work we show that the 120-nucleotide-long 5'
      UTR of RNA-A contains an internal ribosome entry site (IRES) that functions
      efficiently both in vitro and in salmon cells. IRES activity is strongly
      dependent on temperature. Also, the IRES structure is confined to the 5'UTR and
      is not affected by the viral coding sequence. This is the first report of IRES
      activity in a fish virus and can give us tools to generate antivirals to attack
      the virus without affecting fish directly.

PMID- 28743465
TI  - Nanomaterial applications for neurological diseases and central nervous system
      injury.
AB  - The effectiveness of noninvasive treatment for neurological disease is generally
      limited by the poor entry of therapeutic agents into the central nervous system
      (CNS). Most CNS drugs cannot permeate into the brain parenchyma because of the
      blood-brain barrier thus, overcoming this problem has become one of the most
      significant challenges in the development of neurological therapeutics.
      Nanotechnology has emerged as an innovative alternative for treating neurological
      diseases. In fact, rapid advances in nanotechnology have provided promising
      solutions to this challenge. This review highlights the applications of
      nanomaterials in the developing neurological field and discusses the evidence for
      their efficacies.

PMID- 28743466
TI  - Corrigendum to "Orthotopic non-metastatic and metastatic oral cancer mouse
      models" [Oral Oncol. 51(5) (2015) 476-482].

PMID- 28743467
TI  - Basal cell adenocarcinoma of the skull base: A diagnostic challenge.

PMID- 28743468
TI  - Hemoglobin A1c values in CKDu endemic and non endemic regions of Sri Lanka.

PMID- 28743469
TI  - Energy and food intake are associated with specific intestinal parasitic
      infections in children of rural Mexico.

PMID- 28743464
TI  - Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant
      secondary cell death mechanisms.
AB  - Ischemic stroke is a leading cause of death worldwide. A key secondary cell death
      mechanism mediating neurological damage following the initial episode of ischemic
      stroke is the upregulation of endogenous neuroinflammatory processes to levels
      that destroy hypoxic tissue local to the area of insult, induce apoptosis, and
      initiate a feedback loop of inflammatory cascades that can expand the region of
      damage. Stem cell therapy has emerged as an experimental treatment for stroke,
      and accumulating evidence supports the therapeutic efficacy of stem cells to
      abrogate stroke-induced inflammation. In this review, we investigate clinically
      relevant stem cell types, such as hematopoietic stem cells (HSCs), mesenchymal
      stem cells (MSCs), endothelial progenitor cells (EPCs), very small embryonic-like
      stem cells (VSELs), neural stem cells (NSCs), extraembryonic stem cells, adipose
      tissue-derived stem cells, breast milk-derived stem cells, menstrual blood
      derived stem cells, dental tissue-derived stem cells, induced pluripotent stem
      cells (iPSCs), teratocarcinoma-derived Ntera2/D1 neuron-like cells (NT2N), c
      mycER(TAM) modified NSCs (CTX0E03), and notch-transfected mesenchymal stromal
      cells (SB623), comparing their potential efficacy to sequester stroke-induced
      neuroinflammation and their feasibility as translational clinical cell sources.
      To this end, we highlight that MSCs, with a proven track record of safety and
      efficacy as a transplantable cell for hematologic diseases, stand as an
      attractive cell type that confers superior anti-inflammatory effects in stroke
      both in vitro and in vivo. That stem cells can mount a robust anti-inflammatory
      action against stroke complements the regenerative processes of cell replacement
      and neurotrophic factor secretion conventionally ascribed to cell-based therapy
      in neurological disorders.

PMID- 28743470
TI  - Molecular identification and antigenic characterization of Babesia divergens
      Erythrocyte Binding Protein (BdEBP) as a potential vaccine candidate.
AB  - Host cell invasion is the only step where Babesia parasites are extracellular,
      and their survival is menaced during this step. Therefore, interfering with this
      critical stage is a target for an anti-Babesia intervention strategy. In this
      regard, recombinant protein encoding Babesia divergens Erythrocyte Binding
      Protein (BdEBP) was produced in Escherichia coli in the current study, and its
      antiserum was prepared in mice for further molecular characterization. Western
      blotting and indirect fluorescent antibody test (IFAT) revealed the specific
      reaction of the anti-rBdEBP serum with a corresponding authentic protein of B.
      divergens. Next, bovine RBCs were incubated with a B. divergens lysate, and anti
      rBdEBP serum was produced in mice to detect the ability of BdEBP to bind with
      host cells. Bands corresponding to 29.6-kDa proteins in the protein-bound
      erythrocyte lysate were detected by specific immune rBdEBP using Western
      blotting. These results suggest that BdEBP is functional in the merozoite stage
      and may be involved in attachment to bovine RBCs. A significant inhibition of the
      in vitro growth of B. divergens culture treated with anti-rBdEBP serum was
      observed. Moreover, the efficacy of pre-incubated free merozoites to invade
      bovine erythrocytes was inhibited by 60% after incubation with 2mg/ml of anti
      rBdEBP serum for 6h. The obtained data suggest the possible use of rBdEBP as a
      vaccine candidate against bovine babesiosis.

PMID- 28743471
TI  - Diagnosis and Treatment of Clinical Rumen Acidosis.
AB  - Clinical rumen acidosis is an important cause of morbidity and mortality in both
      large and small ruminants. Feeding and management practices that lead to the
      consumption of large amounts of readily fermentable carbohydrates precipitate
      clinical disease. The fermentation of carbohydrates into volatile fatty acids and
      lactate causes acidosis (local and systemic), rumen ulceration, cardiovascular
      compromise, and organ dysfunction. Animals affected with acidosis can suffer from
      numerous sequelae. Treatment of animals with clinical rumen acidosis is focused
      on addressing plasma volume deficits, correcting acid-base disturbances, and
      restoring a normal rumen microenvironment.

PMID- 28743472
TI  - Digestive Disorders of the Ruminant Forestomach.

PMID- 28743473
TI  - Diagnosis and Treatment of Hardware Disease.
AB  - Eating habits in cattle are less discriminant than other ruminants, and they more
      often accidentally ingest strange objects while feeding. Penetrating foreign
      bodies may cause mild to severe peritonitis, penetrate the diaphragm to cause
      pleuritis or pericarditis, or cause localized abscesses in the thorax or abdomen.
      Because these objects are most often metal, a common term for this problem is
      hardware disease. An accurate history and thorough physical examination often
      yields a diagnosis; however, ancillary diagnostics can enhance accuracy and
      disease magnitude before exploratory surgery. Treatment encompasses controlling
      infection and inflammation and foreign body removal; preventive measures are
      emphasized.

PMID- 28743474
TI  - Corrigendum to "Gene networks and transcription factor motifs defining the
      differentiation of human stem cells into hepatocyte-like cells" [J Hepatol
      2015;63:934-942].

PMID- 28743475
TI  - Preventive effects of motorcycle helmets on intracranial injury and mortality
      from severe road traffic injuries.
AB  - INTRODUCTION: Road traffic injuries caused by motorcycle crashes are one of the
      major public health burdens leading to high mortality, functional disability, and
      high medical costs. The helmet is crucial protective equipment for motorcyclists.
      This study aimed to measure the protective effect of motorcycle helmets on
      clinical outcomes and to compare the effects of high- and low-speed motorcycle
      crashes. METHODS: A cross-sectional observational study was conducted using a
      nationwide registry of severe trauma patients treated by emergency medical
      services (EMS) providers in Korea. The study population consisted of severe
      trauma patients injured in motorcycle crashes between January and December 2013.
      The primary and secondary outcomes were intracranial injury and in-hospital
      mortality. We calculated adjusted odds ratios (AORs) of helmet use and motorcycle
      speeds for study outcomes after adjusting for potential confounders. RESULTS:
      Among 495 eligible patients, 105 (21.2%) patients were wearing helmets at the
      time of the crash, and 256 (51.7%) patients had intracranial injuries. The
      helmeted group was less likely to have an intracranial injury compared with the
      un-helmeted group (41.0% vs. 54.6%, AOR: 0.53 (0.33-0.84)). However, there was no
      significant difference in in-hospital mortality between the two groups (16.2% vs.
      16.9%, AOR: 0.91 (0.49-1.69)). In the interaction analysis, there was a
      significant preventive effect of motorcycle helmet use on intracranial injury
      when the speed of the motorcycle was <30km/h (AOR: 0.50 (0.27-0.91)). CONCLUSION:
      Wearing helmets for severe trauma patients in motorcycle crashes reduced
      intracranial injuries. The preventive effect on intracranial injury was
      significant in low-speed motorcycle crashes.

PMID- 28743476
TI  - Creating a diagnostic decision rule for shoulder injury: CASH-trial, a cross
      sectional interobserver study.

PMID- 28743477
TI  - Psychological scales as predictors of emergency department hospitalizations in
      suicide attempters.
AB  - BACKGROUND: The purpose of this study was to evaluate the psychological scales
      reflecting lethality and intent as predictors of suicide attempter's
      hospitalization. METHODS: Data of suicide attempters aged over 15years, who
      visited the ED from January 2013 to June 2016, were retrospectively collected and
      they were divided into the hospitalization and discharge groups. We evaluated the
      Risk-Rescue Rating Scale (RRRS) and Self-Inflicted Injury Severity Form (SIISF)
      for lethality and Suicide Intent Scale (SIS) for intent, respectively. The
      predictive abilities of these scales for hospitalization were compared in terms
      of performance (AUCs) and goodness-of-fit (the Bayesian information criterion
      [BIC]). RESULTS: A total of 382 suicide attempters were enrolled, of which 233
      (61%) were hospitalized. The scores of all psychological scales were
      significantly higher in the hospitalization group and all scales were identified
      as independent predictors of hospitalization. The AUC of the RRRS tended to be
      higher than those of the SIS and SIISF; similarly, the RRRS demonstrated the best
      overall fit (the lowest BIC). The AUC of combined the RRRS and SIS was superior
      to that of any of the individual scales alone. While the AUC of combined the
      SIISF and SIS was superior to that of either individual scale, it was comparable
      to that of the RRRS. CONCLUSIONS: The psychological scales can be helpful for
      predicting suicide attempter's hospitalization in emergency settings. Especially,
      the RRRS seemed to have a superior predictive ability. Moreover, combining the
      scales had significantly better predictive performance than use of the individual
      scale alone did.

PMID- 28743478
TI  - Comparison of different methods of size classification of primary spontaneous
      pneumothorax.

PMID- 28743479
TI  - Integrating heart rate variability, vital signs, electrocardiogram, and troponin
      to triage chest pain patients in the ED.
AB  - BACKGROUND: Current triage methods for chest pain patients typically utilize
      symptoms, electrocardiogram (ECG), and vital sign data, requiring interpretation
      by dedicated triage clinicians. In contrast, we aimed to create a quickly
      obtainable model integrating the objective parameters of heart rate variability
      (HRV), troponin, ECG, and vital signs to improve accuracy and efficiency of
      triage for chest pain patients in the emergency department (ED). METHODS: Adult
      patients presenting to the ED with chest pain from September 2010 to July 2015
      were conveniently recruited. The primary outcome was a composite of
      revascularization, death, cardiac arrest, cardiogenic shock, or lethal arrhythmia
      within 72-h of presentation to the ED. To create the chest pain triage (CPT)
      model, logistic regression was done where potential covariates comprised of vital
      signs, ECG parameters, troponin, and HRV measures. Current triage methods at our
      institution and modified early warning score (MEWS) were used as comparators.
      RESULTS: A total of 797 patients were included for final analysis of which 146
      patients (18.3%) met the primary outcome. Patients were an average age of 60years
      old, 68% male, and 56% triaged to the most acute category. The model consisted of
      five parameters: pain score, ST-elevation, ST-depression, detrended fluctuation
      analysis (DFA) alpha1, and troponin. CPT model>0.09, CPT model>0.15, current
      triage methods, and MEWS>=2 had sensitivities of 86%, 74%, 75%, and 23%,
      respectively, and specificities of 45%, 71%, 48%, and 78%, respectively.
      CONCLUSION: The CPT model may improve current clinical triage protocols for chest
      pain patients in the ED.

PMID- 28743480
TI  - The influence of insurance type on interfacility pediatric emergency department
      transfers.
AB  - BACKGROUND: Disparities exist in the care children receive in the emergency
      department (ED) based on their insurance type. It is unknown if these differences
      exist among children transferred from outside EDs to pediatric tertiary care EDs.
      OBJECTIVE: To compare reasons for transfer and services received at pediatric
      tertiary care EDs between children with private and public insurance. METHODS: We
      performed a secondary analysis of a multicenter survey of ED providers
      transferring patients to pediatric tertiary care EDs in three major U.S. cities.
      Risk differences (RD) and 95% confidence intervals (CI) were calculated to
      compare reasons for transfer and care received at pediatric tertiary care EDs
      based on insurance type. RESULTS: There were 561 surveys completed by
      transferring providers describing reasons for transfer to pediatric tertiary care
      EDs with 52.2% of patients with private insurance and 47.8% with public
      insurance. We found no significant differences between privately and publicly
      insured children in reason for transfer for subspecialty consultation or need for
      admission. We found no significant differences in frequency of admission,
      radiologic studies, or ED procedures at the receiving facilities. However, a
      greater proportion of privately insured children had a subspecialty consultation
      at receiving facilities compared to publicly insured children (RD 9.7, 95% CI 2.0
      to 17.4). CONCLUSIONS: Transferred pediatric patients with private insurance were
      more likely to have subspecialty consultations than children with public
      insurance. Further studies are needed to better characterize the interplay
      between patients' insurance type and both the request for, and the provision of,
      ED subspecialty consultations.

PMID- 28743481
TI  - Prevalence and prognostic relevance of atrial fibrillation in patients with
      Takotsubo syndrome.
AB  - BACKGROUND: Takotsubo syndrome (TTS) is associated with a considerable risk of
      complications during the acute phase and substantial long-term mortality rates.
      Concomitant atrial fibrillation may have an impact on outcome in these patients.
      Aim of this study was to assess the prevalence and prognostic relevance of atrial
      fibrillation in TTS. METHODS: We performed an international, multicenter study
      including 387 TTS patients consecutively enrolled at 3 centers. Atrial
      fibrillation was defined as known history before admission or documented episodes
      during hospital stay. Long-term mortality was evaluated in median 2.9years after
      the acute event. RESULTS: Atrial fibrillation was found in 97 TTS patients
      (25.1%) and was associated with older age (p<0.01), less emotional triggers
      (p=0.03), higher incidence of cardiogenic shock (p<0.01), lower left ventricular
      ejection fraction (p<0.01), and a prolonged hospital stay (p<0.01). Determinants
      of atrial fibrillation at admission (n=34 patients; 9.0%) in multivariate
      logistic regression analysis were age (p=0.001) and cardiogenic shock (p=0.013).
      Long-term mortality was significantly higher in TTS patients with as compared to
      patients without atrial fibrillation (35.2% versus 15.3%; hazard ratio 3.02, 95%
      confidence interval 1.90-4.78; p<0.001). In multivariate Cox regression analysis
      atrial fibrillation was identified as an independent determinant of outcome even
      after adjustment for clinical variables, left ventricular functional parameters
      (ballooning pattern, ejection fraction), and cardiogenic shock. CONCLUSIONS: In
      TTS patients, atrial fibrillation is frequent and associated with increased long
      term mortality rates. Furthermore, our study identifies atrial fibrillation as an
      independent predictor of outcome and a potential tool for risk stratification in
      TTS.

PMID- 28743482
TI  - Adult congenital heart disease in Greece: Preliminary data from the CHALLENGE
      registry.
AB  - BACKGROUND: The majority of patients with congenital heart disease (CHD),
      nowadays, survives into adulthood and is faced with long-term complications. We
      aimed to study the basic demographic and clinical characteristics of adult
      patients with congenital heart disease (ACHD) in Greece. METHODS: A registry
      named CHALLENGE (Adult Congenital Heart Disease Registry. A registry from
      Hellenic Cardiology Society) was initiated in January 2012. Patients with
      structural CHD older than 16years old were enrolled by 16 specialized centers
      nationwide. RESULTS: Out of a population of 2115 patients with ACHD, who have
      been registered, (mean age 38years (SD 16), 52% women), 47% were classified as
      suffering from mild, 37% from moderate and 15% from severe ACHD. Atrial septal
      defect (ASD) was the most prevalent diagnosis (33%). The vast majority of ACHD
      patients (92%) was asymptomatic or mildly symptomatic (NYHA class I/II). The most
      symptomatic patients were suffering from an ASD, most often the elderly or those
      under targeted therapy for pulmonary arterial hypertension. Elderly patients
      (>60years old) accounted for 12% of the ACHD population. Half of patients had
      undergone at least one open-heart surgery, while 39% were under cardiac
      medications (15% under antiarrhythmic drugs, 16% under anticoagulants, 16% under
      medications for heart failure and 4% under targeted therapy for pulmonary
      arterial hypertension). CONCLUSIONS: ACHD patients are an emerging patient
      population and national prospective registries such as CHALLENGE are of unique
      importance in order to identify the ongoing needs of these patients and match
      them with the appropriate resource allocation.

PMID- 28743483
TI  - Are adults with congenital heart disease informed about their risk for infective
      endocarditis and treated in accordance to current guidelines?
AB  - BACKGROUND: Adults with congenital heart disease (ACHD) have an increased risk
      for infective endocarditis (IE). In the last decade, the recommendations for IE
      prophylaxis have changed substantially. The knowledge level of patients about IE
      and IE prophylaxis has not been studied. METHODS: Patients recruited via the
      German National Register for Congenital Heart Defects were invited to an online
      survey about IE. Patients were divided into two groups based on ESC guidelines:
      high IE risk (antibiotic prophylaxis recommended) and low IE risk (prophylaxis
      not recommended). RESULTS: Overall, 1458 patients participated and out of these
      1211 (age 30.5+/-11.8years, female=54.2%) with detailed clinical information were
      further analyzed. 343 patients had a high IE risk, whereas 868 had a low risk.
      Overall, 74.5% (n=902) stated to know what IE is (low IE risk: 71.3%, high IE
      risk: 82.5%) Out of these who stated to know what IE is (n=902), 76.5% (n=690)
      chose the correct answer in a multiple choice question (low IE risk: 76.4%; high
      IE risk: 76.7%). Antibiotic prophylaxis was known to 66.2% (low IE risk: 59.9%;
      high IE risk: 82.2%). Out of these who stated to know what antibiotic prophylaxis
      is (n=802), 83.8% (n=672) chose the correct answer in a multiple choice question
      (low IE risk: 82.9%; high IE risk: 85.5%). CONCLUSIONS: This study reveals
      important knowledge gaps regarding IE and antibiotic prophylaxis in ACHD
      patients. A discussion about IE and antibiotic prophylaxis should take place with
      every ACHD patient during regular clinical contacts to close this knowledge gap.

PMID- 28743484
TI  - Oxidative stress enhances and modulates protein S-nitrosation in smooth muscle
      cells exposed to S-nitrosoglutathione.
AB  - Among S-nitrosothiols showing reversible binding between NO and -SH group, S
      nitrosoglutathione (GSNO) represents potential therapeutics to treat
      cardiovascular diseases (CVD) associated with reduced nitric oxide (NO)
      availability. It also induces S-nitrosation of proteins, responsible for the main
      endogenous storage form of NO. Although oxidative stress parallels CVD
      development, little is known on the ability of GSNO to restore NO supply and
      storage in vascular tissues under oxidative stress conditions. Aortic rat smooth
      muscle cells (SMC) were stressed in vitro with a free radical generator (2,2'
      azobis(2-amidinopropane) dihydrochloride, AAPH). The cellular thiol redox status
      was reflected through levels of reduced glutathione and protein sulfhydryl (SH)
      groups. The ability of GSNO to deliver NO to SMC and to induce protein S
      nitrosation (investigated via mass spectrometry, MS), as well as the implication
      of two redox enzymes involved in GSNO metabolism (activity of gamma
      glutamyltransferase, GGT, and expression of protein disulfide isomerase, PDI)
      were evaluated. Oxidative stress decreased both intracellular glutathione and
      protein -SH groups (53% and 32% respectively) and caused a 3.5-fold decrease of
      GGT activity, while PDI expression at the plasma membrane was 1.7-fold increased
      without any effect on extracellular GSNO catabolism. Addition of GSNO (50 MUM)
      increased protein -SH groups and protein S-nitrosation (50%). Mass spectrometry
      analysis revealed a higher number of S-nitrosated proteins under oxidative stress
      (83 proteins, vs 68 in basal conditions) including a higher number of
      cytoskeletal proteins (15, vs 9 in basal conditions) related with cell
      contraction, morphogenesis and movement. Furthermore, proteins belonging to
      additional protein classes (cell adhesion, transfer/carrier, and transporter
      proteins) were S-nitrosated under oxidative stress. In conclusion, higher levels
      of GSNO-dependent S-nitrosation of proteins from the cytoskeleton and the
      contractile machinery were identified under oxidative stress conditions. The
      findings may prompt the identification of suitable biomarkers for the appraisal
      of GSNO bioactivity in the CVD treatment.

PMID- 28743485
TI  - Content of web-based continuing medical education about HPV vaccination.
AB  - BACKGROUND: Addressing low HPV vaccination coverage will require U.S. health care
      providers to improve their recommendation practices and vaccine delivery systems.
      Because readily available continuing medical education (CME) could be an
      important tool for supporting providers in this process, we sought to assess the
      content of web-based CME activities related to HPV vaccination. METHODS: We
      conducted a content analysis of web-based CME activities about HPV vaccination
      available to U.S. primary care providers in May-September 2016. Using search
      engines, educational clearinghouses, and our professional networks, we identified
      15 activities eligible for study inclusion. Through a process of open coding, we
      identified 45 commonly occurring messages in the CME activities, which we
      organized into five topic areas: delivering recommendations for HPV vaccination,
      addressing common parent concerns, implementing office-based strategies to
      increase HPV vaccination coverage, HPV epidemiology, and guidelines for HPV
      vaccine administration and safety. Using a standardized abstraction form, two
      coders then independently assessed which of the 45 messages each CME activity
      included. RESULTS: CME activities varied in the amount of content they delivered,
      with inclusion of the 45 messages ranging from 17% to 86%. Across activities, the
      most commonly included messages were related to guidelines for HPV vaccine
      administration and safety. For example, all activities (100%) specified that
      routine administration is recommended for ages 11 and 12. Most activities (73%)
      also noted that provider recommendations are highly influential. Fewer activities
      modeled examples of effective recommendations (47%), gave specific approaches to
      addressing common parent concerns (47%), or included guidance on office-based
      strategies to increase coverage (40%). CONCLUSIONS: Given that many existing CME
      activities lack substantive content on how to change provider practice, future
      activities should focus on the practical application of interpersonal and
      organizational approaches for improving HPV vaccine delivery in the clinical
      setting.

PMID- 28743486
TI  - Targeting interferon-alpha to dendritic cells enhances a CD8+ T cell response to
      a human CD40-targeted cancer vaccine.
AB  - Targeting antigens to antigen presenting cells (APC) enhances the potency of
      recombinant protein CD8+ T cell vaccines. Recent comparisons of recombinant
      protein-based dendritic cell (DC) targeting vaccines revealed differences in
      cross-presentation and identified CD40 as a potent human DC receptor target for
      antigen cross-presentation. Contrary to in vitro-derived monocyte (mo)DC, we
      found that interferon-alpha (IFNalpha) stimulation of human blood-derived DC was
      necessary for an antigen-specific IFNgamma CD8+ T cell response to a CD40
      targeted cancer vaccine. Importantly, targeting an adjuvant in the form of
      IFNalpha to DC increased their potency to elicit antigen-specific production of
      IFNgamma by CD8+ T cells. Thus, we introduce the concept of DC adjuvant targeting
      to enhance the potency of vaccination.

PMID- 28743487
TI  - Hepatitis B vaccines: WHO position paper, July 2017 - Recommendations.
AB  - This article presents the World Health Organization's (WHO) recommendations on
      the use of hepatitis B vaccines excerpted from the Hepatitis B vaccines: WHO
      position paper, July 2017, published in the Weekly Epidemiological Record
      (Hepatitis B vaccines, 2017) [1]. This position paper replaces the May 2009 WHO
      position paper on hepatitis B vaccines (Hepatitis B vaccines, 2009) [2]. The
      position paper gives updated information on hepatitis B vaccines and their
      storage, transport and deployment. The recommendations concern the target groups
      for vaccination and the appropriate schedules. In particular, the recommendations
      stress the importance of vaccination of all infants at birth as the most
      effective intervention for the prevention of hepatitis B virus-associated disease
      worldwide. Footnotes to this paper provide a number of core references including
      references to grading tables that assess the quality of the scientific evidence,
      and to the evidence-to-recommendation table. In accordance with its mandate to
      provide guidance to Member States on health policy matters, WHO issues a series
      of regularly updated position papers on vaccines and combinations of vaccines
      against diseases that have an international public health impact. These papers
      are concerned primarily with the use of vaccines in large-scale immunization
      programmes; they summarize essential background information on diseases and
      vaccines, and conclude with WHO's current position on the use of vaccines in the
      global context. Recommendations on the use of hepatitis B vaccines were discussed
      by SAGE in October 2016; evidence presented at these meetings can be accessed at:
      http://www.who.int/immunization/sage/meetings/2016/October/presentations_backgrou
      d_docs/en/.

PMID- 28743488
TI  - Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?
AB  - Biased activation of G-protein-coupled receptors (GPCRs) is shifting drug
      discovery efforts and appears promising for the development of safer drugs. The
      most effective analgesics to treat acute pain are agonists of the MU opioid
      receptor (MU-OR), a member of the GPCR superfamily. However, the analgesic use of
      opioid drugs, such as morphine, is hindered by adverse effects. Only a few MU-OR
      agonists have been reported to selectively activate the Gi over beta-arrestin
      signaling pathway, resulting in lower gastrointestinal dysfunction and
      respiratory suppression. Here, we discuss the strategies that led to the
      development of biased MU-OR agonists, and potential areas for improvement, with
      an emphasis on structural aspects of the ligand-receptor recognition process.

PMID- 28743489
TI  - Lipid profiling of the filarial nematodes Onchocerca volvulus, Onchocerca ochengi
      and Litomosoides sigmodontis reveals the accumulation of nematode-specific ether
      phospholipids in the host.
AB  - Onchocerciasis, a neglected tropical disease prevalent in western and central
      Africa, is a major health problem and has been targeted for elimination. The
      causative agent for this disease is the human parasite Onchocerca volvulus.
      Onchocerca ochengi and Litomosoides sigmodontis, infectious agents of cattle and
      rodents, respectively, serve as model organisms to study filarial nematode
      infections. Biomarkers to determine infection without the use of painful skin
      biopsies and microscopic identification of larval worms are needed and their
      discovery is facilitated by an improved knowledge of parasite-specific
      metabolites. In addition to proteins and nucleic acids, lipids may be suitable
      candidates for filarial biomarkers that are currently underexplored. To fill this
      gap, we present the phospholipid profile of the filarial nematodes O. ochengi, O.
      volvulus and L. sigmodontis. Direct infusion quadrupole time-of-flight (Q-TOF)
      mass spectrometry was employed to analyze the composition of phospholipids and
      their molecular species in the three nematode species. Analysis of the
      phospholipid profiles of plasma or serum of uninfected and infected hosts showed
      that nematode-specific phospholipids were below detection limits. However,
      several phospholipids, in particular ether lipids of phosphatidylethanolamine
      (PE), were abundant in O. ochengi worms and in bovine nodule fluid, suggesting
      that these phospholipids might be released from O. ochengi into the host, and
      could serve as potential biomarkers.

PMID- 28743490
TI  - Clinical relationship of meibometry with ocular symptoms and tear film stability.
AB  - PURPOSE: To evaluate the relationship between meibometry with both ocular
      symptoms and tear film stability by: (1) to find out whether meibometry is able
      to differentiate between dry eye symptomatic and asymptomatic subjects classified
      by standardized dry eye questionnaires (OSDI and McMonnies), and (2) to assess
      the clinical relationship between meibometry with both tear break-up time (BUT)
      and maximum blink interval (MBI). METHODS: 140 Patients were recruited for the
      study. Using Meibometer MB550, five curves were generated for each patient.
      Subjects performed OSDI and McMonnies questionnaires and were stratified
      following a two- and a three-subgroup stratification for each questionnaire.
      BUT/MBI were repeated three times (by video recordings), and they were determined
      by counting their frames. RESULTS: Subjects grouped by OSDI showed a trend to
      present lower meibometry values as the OSDI score were higher (ANOVA, p<=0.044).
      For McMonnies questionnaire this was only true for the two-subgroup
      stratification (ANOVA, p=0.04), but not for three-subgroup stratification (one
      way ANOVA, p=0.30). On the other hand, meibometry values showed a statistical
      correlation with both BUT (r=0.305, p<0.001) and MBI (r=0.265, p<0.001). When the
      sample was divided in three groups regarding BUT value (<=5s, between 5 and 10s
      and>=10s), significant differences of meibometry values were found between BUT
      subgroups (p=0.008). CONCLUSION: Meibometer MB550 can discriminate asymptomatic
      from dry eye symptomatic patients. Furthermore, there is a relationship between
      meibometry and the tear film stability.

PMID- 28743491
TI  - Individualized risk estimation for postoperative morbidity after hepatectomy: the
      Humanitas score.
AB  - BACKGROUND: Estimation of postoperative morbidity after hepatectomy remains
      challenging. The aim of this prospective study was to develop a surgical score to
      predict an individual risk of post-hepatectomy complications. METHODS: All
      consecutive patients scheduled for hepatectomy from February 2012 to September
      2015 were included and randomly assigned into a derivation or validation cohort.
      We developed a score based on preoperative variables, and we tested them using
      multivariate analyses. Odds-ratio (OR) values were used to build the score.
      RESULTS: 340 patients were included, 240 in the derivation and 100 in the
      validation cohort. Multivariate analysis showed that major hepatectomy (OR =
      1.62; 95% CI 1.39-3.51), liver stiffness >=9.7 kPa (OR = 2.46; 95% CI 1.16-5.28),
      BILCHE score (combination of serum bilirubin and cholinesterase) >=2 (OR = 2.76;
      95% CI 0.82-4.28) and esophageal varices (OR = 1.59; 95% CI 1.51-3.61) were
      independent complications predictors. A 10-point scoring system was introduced.
      Patients with a score <=4 did not experience complications, whereas patients with
      >=7 points experienced up to 54% of complications (P < 0.001). CONCLUSIONS: A
      new, easy and clinically reliable surgical score based on the liver stiffness,
      BILCHE score, type of hepatectomy, and presence of varices may be used to predict
      post-hepatectomy morbidity. CLINICAL TRIAL NUMBER: NCT02454686
      (https://www.clinicaltrials.gov/).

PMID- 28743492
TI  - 5-Bromoindirubin 3'-(O-oxiran-2-ylmethyl)oxime: A long-acting anticancer agent
      and a suicide inhibitor for epoxide hydrolase.
AB  - Indirubin 3'-oxime (Indox (1b)) suppresses cancer cell growth (IC50: 15MUM
      towards HepG2 cells) and inhibits cell cycle-related kinases such as cyclin
      dependent kinases and glycogen synthase kinase-3beta. We have previously reported
      that the conjugation of 1b with oxirane, a protein-reactive component, enhanced
      the cytotoxic activity of Indox as determined from the IC50 value (1.7MUM) of
      indirubin 3'-(O-oxiran-2-ylmethyl)oxime (Epox/Ind (1c)). Here we prepared
      Epox/Ind derivatives with one or two halogen atoms or a methoxy group on the
      aromatic ring(s) of an Indox moiety and studied the structure-activity
      relationships of the substituent(s). We found that bromine-substitution at the 5
      position on 1c or any Epox/Ind derivative(s) having bromine on the aromatic ring
      except Epox/6'-Br-Ind was efficient to improving anticancer activity. Of the 22
      Epox/Ind derivatives, 5-bromoindirubin 3'-(O-oxiran-2-ylmethyl)oxime (Epox/5-Br
      Ind (2c)) was the best anticancer agent in both short- (24h) (IC50: 0.67MUM) and
      extended-duration (72h) cultures. The high anticancer activity of 2c was partly
      due to it being a poor substrate and a suicide inhibitor for epoxide hydrolase as
      epoxide hydrolase was identified as the enzyme primarily responsible for the
      metabolism of 2c.

PMID- 28743493
TI  - Dimensions of physical punishment and their associations with children's
      cognitive performance and school adjustment.
AB  - This study examined how a range of physical punishment measures, ranging from
      mild corporal punishment to physical abuse, are associated with cognitive
      performance, school engagement, and peer isolation over a 3- year span among 658
      children initially observed between the ages of 8 and 14. Physical punishment was
      captured in three groups: mild corporal punishment, harsh corporal punishment,
      and physical abuse, and both caregiver- and child-reported punishment measures
      were considered. After accounting for socioeconomic and demographic
      characteristics, only Ninitial exposure to physical abuse was significantly
      associated with declines in cognitive performance. However, all forms of physical
      punishment were associated with declines in school engagement, and harsh corporal
      punishment was associated with increased peer isolation. Our findings were
      relatively consistent regardless of whether physical punishment was reported by
      the child or caregiver. Overall, our findings suggest that the prevention of
      physical abuse may enhance children's cognitive performance, but that alone may
      not be sufficient to ensure children are engaged and well-adjusted in school.

PMID- 28743494
TI  - Neural Glycosylphosphatidylinositol-Anchored Proteins in Synaptic Specification.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins are a specialized class of
      lipid-associated neuronal membrane proteins that perform diverse functions in the
      dynamic control of axon guidance, synaptic adhesion, cytoskeletal remodeling, and
      localized signal transduction, particularly at lipid raft domains. Recent studies
      have demonstrated that a subset of GPI-anchored proteins act as critical
      regulators of synapse development by modulating specific synaptic adhesion
      pathways via direct interactions with key synapse-organizing proteins. Additional
      studies have revealed that alteration of these regulatory mechanisms may underlie
      various brain disorders. In this review, we highlight the emerging role of GPI
      anchored proteins as key synapse organizers that aid in shaping the properties of
      various types of synapses and circuits in mammals.

PMID- 28743495
TI  - Association Between Physical Activity, Depression, and Diabetes in Urban-Dwelling
      People Living with HIV.
AB  - Physical activity (PA) may improve physical and mental health in people living
      with HIV (PLWH). However, the associations between PA participation and physical
      and mental health problems of PLWH in urban settings remain largely unknown. Our
      objective was to determine the relationships between PA and physical and mental
      health in urban-dwelling PLWH. There were 289 adult PLWH who responded to an
      electronic survey including questions on PA and current physical and mental
      health. The associations between physical and mental health and PA were
      investigated using linear and logistic regression. A large proportion of
      participants met recommended volumes of PA. Eighty-three percent of respondents
      reported symptoms of severe mental distress. Diabetes mellitus was associated
      with a lower total volume of PA (p = .035). Similarly, depression was negatively
      associated with muscle-strengthening exercise participation (p = .030).
      Sufficient amounts of aerobic activity and/or muscle strengthening exercise are
      associated with better physical and mental health.

PMID- 28743496
TI  - WNK4 is indispensable for the pathogenesis of pseudohypoaldosteronism type II
      caused by mutant KLHL3.
AB  - WNK-OSR1/SPAK-NCC signaling cascade is important for regulating salt balance and
      blood pressure. Activation of WNK-OSR1/SPAK-NaCl cotransporter (NCC) cascade
      increases sodium reabsorption in the kidney, leading to pseudohypoaldosteronism
      type II (PHA II) characterized by salt-sensitive hypertension and hyperkalemia.
      It has been previously demonstrated that the amount of phosphorylated and total
      NCC markedly decreased in WNK4-/- mice, indicating that WNK4 plays a major role
      for activation of OSR1/SPAK-NCC signaling. However, it is unclear whether absence
      of WNK4 can be compensated by other WNK kinases. We recently reported that
      KLHL3R528H/+ knock-in mice, a PHAII model, exhibited augmented activation of
      OSR1/SPAK-NCC signaling by increased protein levels of both WNK1 and WNK4 due to
      impaired protein degradation by the mutant KLHL3. In this study, we sought to
      determine the contribution of WNK4 to OSR1/SPAK-NCC signaling using an in vivo
      model which shows extremely increased WNK1 with absence of WNK4. We generated
      WNK4-/-KLHL3R528H/+ mice and WNK4-/-KLHL3R528H/R528H mice by crossing WNK4-/-
      mice with KLHL3R528H/+ mice. Thereafter, WNK-OSR1/SPAK-NCC phosphorylation signal
      cascade was examined in kidneys from these mice. As expected, both WNK4-/
      KLHL3R528H/+ mice and WNK4-/-KLHL3R528H/R528H mice demonstrated increased WNK1 in
      the kidney, due to the KLHL3 mutation, and WNK4 deficiency. However,
      phosphorylation of SPAK and NCC at distal convoluted tubules were almost
      completely absent even in WNK4-/-KLHL3R528H/R528H mice. In conclusion, increased
      WNK1 was unable to compensate for WNK4 deficiency and phosphorylate the NCC,
      indicating that WNK4 is indispensable for the onset of PHAII.

PMID- 28743497
TI  - Molecular interaction between K-Ras and H-REV107 in the Ras signaling pathway.
AB  - Ras proteins are small GTPases that serve as master moderators of a large number
      of signaling pathways involved in various cellular processes. Activating
      mutations in Ras are found in about one-third of cancers. H-REV107, a K-Ras
      binding protein, plays an important role in determining K-Ras function. H-REV107
      is a member of the HREV107 family of class II tumor suppressor genes and a growth
      inhibitory Ras target gene that suppresses cellular growth, differentiation, and
      apoptosis. Expression of H-REV107 was strongly reduced in about 50% of human
      carcinoma cell lines. However, the specific molecular mechanism by which H-REV107
      inhibits Ras is still unknown. In the present study, we suggest that H-REV107
      forms a strong complex with activating oncogenic mutation Q61H K-Ras from various
      biochemical binding assays and modeled structures. In addition, the interaction
      sites between K-Ras and H-REV107 were predicted based on homology modeling. Here,
      we found that some structure-based mutants of the K-Ras disrupted the complex
      formation with H-REV107. Finally, a novel molecular mechanism describing K-Ras
      and H-REV107 binding is suggested and insights into new K-Ras effector target
      drugs are provided.

PMID- 28743498
TI  - Hydrogen-rich medium protects mouse embryonic fibroblasts from oxidative stress
      by activating LKB1-AMPK-FoxO1 signal pathway.
AB  - Persistent oxidative stress is recognized as a major cause of many pathological
      conditions as well as ageing. However, most clinical trials of dietary
      antioxidants have failed to produce successful outcomes in treating oxidative
      stress-induced diseases. Molecular hydrogen (H2) has recently received
      considerable attention as a therapeutic agent owing to its novel antioxidant
      properties, a selective scavenger of hydroxyl and peroxynitrite radicals. Beyond
      this, numerous reports support that H2 can modulate the activity of various
      cellular signal pathways. However, its effect on AMP-activated protein kinase
      (AMPK) signal pathway, a central regulator of energy hemostasis, has remained
      almost elusive. Here, we report that hydrogen-rich medium activated LKB1-AMPK
      signal pathway without ATP depletion, which in turn induced FoxO1-dependent
      transcription of manganese superoxide dismutase and catalase in mouse embryonic
      fibroblasts. Moreover, hydrogen-rich media effectively reduced the level of
      reactive oxygen species in cells treated with hydrogen peroxide and protected
      these cells from apoptosis in an AMPK-dependent manner. These results suggest
      that the LKB1-AMPK-FoxO1 signaling pathway is a critical mediator of the
      antioxidant properties of H2, further supporting the idea that H2 acts as a
      signaling molecule to serve various physiological functions.

PMID- 28743499
TI  - All-trans retinoic acid attenuates bleomycin-induced pulmonary fibrosis via
      downregulating EphA2-EphrinA1 signaling.
AB  - The role of all-trans retinoic acid (ATRA) in pulmonary fibrosis is relatively
      unknown, although this metabolite modulates cell differentiation, proliferation,
      and development. We aimed to evaluate the role of ATRA in bleomycin-induced
      pulmonary fibrosis, and whether the mechanism involves EphA2-EphrinA1 and PI3K
      Akt signaling. We evaluated three groups of mice: a control group
      (intraperitoneal DMSO injection 3 times weekly after PBS instillation), bleomycin
      group (intraperitoneal DMSO injection 3 times weekly after bleomycin
      instillation), and bleomycin + ATRA group (intraperitoneal ATRA injection 3 times
      weekly after bleomycin instillation). The cell counts and protein concentration
      in the bronchoalveolar lavage fluid (BALF), changes in histopathology, Ashcroft
      score, hydroxyproline assay, expression of several signal pathway proteins
      including EphA2-EphrinA1, and PI3K-Akt, and cytokine levels were compared among
      the groups. We found that bleomycin significantly increased the protein
      concentration in the BALF, Ashcroft score in lung tissue, and hydroxyproline
      contents in lung lysates. Furthermore, bleomycin upregulated EphA2, EphrinA1,
      PI3K 110gamma, Akt, IL-6 and TNF-alpha. However, administration of ATRA
      attenuated the upregulation of EphA2-EphrinA1 and PI3K-Akt after bleomycin
      instillation, and decreased pulmonary fibrosis. In addition, ATRA suppressed IL-6
      and TNF-alpha production induced by bleomycin-induced injury. Collectively, these
      data suggest that ATRA attenuates bleomycin-induced pulmonary fibrosis by
      regulating EphA2-EphrinA1 and PI3K-Akt signaling.

PMID- 28743500
TI  - Suppression of Npr1, not Npr2 gene function induces hypertrophic growth in H9c2
      cells in vitro.
AB  - Npr1 gene (coding for NPR-A) and Npr2 gene (coding for NPR-B) are identified as
      intrinsic anti-hypertrophic genes that opposes abnormal cardiac remodeling.
      However, the functional role of Npr1 and Npr2 genes during cardiac hypertrophic
      growth is not well understood. Hence, the present investigation was aimed to
      study the effect of Npr1 and Npr2 gene silencing, respectively on beta-AR
      activation induced cardiac hypertrophic growth in H9c2 cells in vitro. The
      control, Npr1, and Npr2 gene suppressed H9c2 cells, respectively were treated
      with ISO (10-5 M) for 48 h. The mRNA and protein expression profile of NPR-A, NPR
      B, PKG-I and cGMP were analyzed by qPCR, Western blotting, ELISA, and
      immunofluorescence methods, respectively. A marked increase in cell size (30.10
      +/- 0.51 MUm vs 61.83 +/- 0.43 MUm, 2-fold) accompanied by elevated hypertrophic
      marker genes (alpha-sk and beta-MHC 3-fold, respectively) expression was observed
      in Npr1 gene suppressed H9c2 cells as compared with control cells. In contrast,
      the Npr2 gene suppression in H9c2 cells neither altered the cell size nor the
      level of hypertrophic marker genes expression. Upon exposure to Isoproterenol,
      the Npr1 suppressed H9c2 cells exhibited further increase in cell size (1.5
      fold), whereas, no significant increase in cell size or marker genes expression
      was noticed in Npr2 suppressed cells. Moreover, the intracellular cGMP level was
      down-regulated by 2-fold in Npr1 suppressed cells, while, no significant change
      was observed in Npr2 suppressed cells. Together, these results suggest that Npr1,
      not Npr2 gene function is positively associated with the initiation of cardiac
      fetal gene program and development of cardiac hypertrophic growth.

PMID- 28743501
TI  - Hypoxic postconditioning attenuates apoptosis via inactivation of adenosine A2a
      receptor through NDRG3-Raf-ERK pathway.
AB  - BACKGROUND: In recent years, many studies have demonstrated that endogenous
      adenosine induced by ischemia postconditioning reduces apoptosis in animal and
      cell models, but no study has clearly elucidated the effects of hypoxia
      postconditioning (HPC) in human dermal microvascular endothelial cells (HDMECs)
      of flaps, and the subtype of adenosine receptors involved remains unknown. In our
      study, we sought to identify the roles of adenosine A2a receptor, NDRG3 (N-myc
      downstream-regulated gene 3) and Raf-ERK pathway in the anti-apoptotic effects of
      hypoxia postconditioning. METHODS: Human dermal microvascular endothelial cells
      were put into a hypoxic incubator (94% N2 + 5% CO2 + 1% O2) for 8 h (hypoxia),
      and followed 24 h of normoxic culture with 95% air and 5% CO2 (reoxygenation).
      Hypoxia postconditioning model of HDMECs was achieved as follows: Before HDMECs
      were put into a normoxic incubator, HDMECs were treated by three cycles of 5 min
      of brief reoxygenation and 5 min of re-hypoxia. Opening level of mitochondrial
      permeability transition pore and change of mitochondrial membrane potential were
      detected with related Kit. The protein expressions of mitochondrion apoptosis,
      adenosine A2a receptor and NDRG3-Raf-ERK pathway were measured by western blot.
      RESULT: Hypoxia/reoxygenation (H/R) resulted in injury in HDMRCs as evidenced by
      an increase in apoptosis percentage, mitochondrial membrane permeability and an
      increase in expression of pro-apoptosis proteins (Bax, c-caspase-3 and cytochrom
      C), meanwhile, hypoxia/reoxygenation increased expression of A2a receptor, NDRG3,
      p-c-Raf, p-ERK, which was significantly attenuated by hypoxia postconditioning
      treatment. Moreover, Hypoxia/reoxygenation (H/R) resulted in a decrease in
      expression of anti-apoptotic protein (Bcl-2). However, the protective effect of
      hypoxia postconditioning treatment could be inhibited by adding CGS21680, a
      selective adenosine A2a receptor agonist (all P values < 0.05).

PMID- 28743502
TI  - Cell autonomous sonic hedgehog signaling contributes to maintenance of retinal
      endothelial tight junctions.

PMID- 28743503
TI  - A multi-centre prospective evaluation of the Check-Direct ESBL Screen for BD MAX
      as a rapid molecular screening method for extended-spectrum beta-lactamase
      producing Enterobacteriaceae rectal carriage.
AB  - OBJECTIVE: A multiplex extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (ESBL-E) quantitative polymerase chain reaction (qPCR),
      performed directly on rectal swabs, was compared with a culture-based protocol to
      study the discrepancies between the two methods, and identify existing challenges
      to apply this assay in routine clinical practice. The secondary objective was to
      assess the performance of the qPCR. MATERIALS AND METHODS: In two Dutch teaching
      hospitals, 573 rectal swabs were collected prospectively. Culture with additional
      testing with the Check-MDR CT103XL (Check-Points) was compared with the Check
      Direct ESBL Screen for BD MAX (Check-Points), which detects the presence of the
      ESBL gene families CTX-M1, CTX-M2, CTX-M9 and SHV2/5-ESBL. The culture-based
      protocol (with Brilliance agar) was considered as the gold standard to assess the
      performance of the qPCR. RESULTS: Of the 573 rectal swabs, 74 (12.9%) were
      culture-positive. Eighty-four (14.7%) were qPCR-positive. There were eight
      culture-positive/qPCR-negative discrepancies and 18 culture-negative/qPCR
      positive discrepancies. Sensitivity and specificity of qPCR vs culture were 87.7%
      [95% confidence interval (CI) 79.7-95.7] and 96.3% (95% CI 94.6-98.0),
      respectively. CONCLUSION: The Check-Direct ESBL Screen for the BD MAX is an easy
      to-perform, quick molecular diagnostic test with the potential to significantly
      speed up screening for rectal ESBL-E carriage. Discrepancies were observed
      between the culture-based protocol and the qPCR in 4.5% of tested samples.
      Existing challenges for implementing qPCR are its limited sensitivity, the need
      for thorough knowledge of the local ESBL-E genes, and interpretation of culture
      negative but qPCR-positive samples. It is believed that the limited sensitivity
      of qPCR could be optimized by including blaTEM as a molecular target, and
      improving the limit of detection.

PMID- 28743504
TI  - The association between infection control interventions and carbapenem-resistant
      Enterobacteriaceae incidence in an endemic hospital.
AB  - BACKGROUND: Israel experienced a national outbreak of carbapenem-resistant
      Enterobacteriaceae (CRE) starting in 2006. AIM: To assess the association between
      infection control (IC) interventions implemented in a referral hospital in Israel
      and CRE incidence. METHODS: Retrospective quasi-experimental study of
      prospectively collected data. CRE incidence, defined as the number of patients
      newly acquiring CRE in surveillance or clinical samples per 100,000 hospital
      days, was plotted quarterly between 2005 and 2016. IC interventions were applied
      at different time-points throughout this period. Data were collected on IC
      staffing, number of rectal surveillance cultures, and carbapenem consumption.
      Autocorrelated segmented linear regression analysis was used to assess the time
      points at which a significant change in the CRE incidence trend occurred, and the
      association between the timing of IC intervention implementation and observed CRE
      trends was assessed. Trends between time-points were expressed as quarterly
      percent change (QPC) with 95% confidence intervals (CIs). FINDINGS: Between 2005
      and 2008, CRE incidence increased significantly (QPC: 19.7%; CI: 11.5-28.4),
      reaching a peak of 186.6 new acquisitions per 100,000 hospital-days. From mid
      2011 until the end of follow-up, there was a significantly decreasing incidence
      trend (QPC: -4.5; CI: -6.4 to -2.5). Cohorting of patients, screening of contacts
      and high-risk patients on admission were insufficient to control the epidemic.
      Improved hand hygiene compliance, cohorting with dedicated nursing staff,
      addition of regular screening in high-risk departments, and carbapenem
      restriction were required. Decreasing CRE incidence was observed with an
      infectious diseases/IC staffing of 1.2-1.5 per 100 beds and 20,000-36,000 yearly
      CRE surveillance samples. CONCLUSION: A multi-faceted hospital-wide intervention
      programme is required to control CRE in hospital settings.

PMID- 28743505
TI  - Short Physical Performance Battery, usual gait speed, grip strength and
      Vulnerable Elders Survey each predict functional decline among older women with
      breast cancer.
AB  - OBJECTIVE: To determine the ability of three performance-based measures [Short
      Physical Performance Battery (SPPB), gait speed, and Grip Strength] and a self
      report measure [Vulnerable Elders Survey (VES-13)] to predict functional decline
      among older women with breast cancer. PATIENTS AND METHODS: Longitudinal data
      from a study of women >=65years, with newly diagnosed stages I-III breast cancer,
      recruited from ambulatory oncology clinics between July 2010 and April 2014, was
      used. The primary outcome was functional decline, Yes or No, defined as a
      decrease in >=1-point from baseline to 12months, on Activities of Daily Living
      Scales. Multivariable logistic regression and receiver operator curve analyses
      were conducted. RESULTS: Among 123 participants 18 (15%) developed functional
      decline. The predictive abilities for measures were: SPPB [Adjusted odds ratio
      (AOR)=1.65 per unit decrease in scores, 95% confidence interval (CI)=1.33-2.05;
      area under the receiver operator curve (AUC)=0.93; sensitivity=94%,
      specificity=80%]; gait speed (AOR=1.76 per unit increase in usual walking time,
      CI=1.29-2.41; AUC=0.93; sensitivity=87%, specificity=79%); VES-13 (AOR=1.64 per
      unit increase in scores, CI=1.31-2.05; AUC=0.87; sensitivity=83%,
      specificity=84%); and grip strength: (AOR=1.18 per unit decrease in grip
      strength, CI=1.06-1.30; AUC=0.80; sensitivity=67%, specificity=77%). CONCLUSION:
      SPPB, gait speed, grip strength and VES-13 all demonstrated excellent predictive
      abilities for functional decline. Larger studies are warranted to confirm the
      utility of these measures for identifying older adults with cancer at increased
      risk for functional decline, who may then be targeted for studies to explore the
      effects of interventions to improve function.

PMID- 28743506
TI  - Risk factors and characteristics of falls among hospitalized adult patients with
      hematologic diseases.
AB  - OBJECTIVES: Falls and fall-related injuries are major problems in hospitals. In
      hematologic patients, both disease and its treatment, including chemotherapy and
      allogeneic hematopoietic cell transplantation (allo-HCT), can cause anemia,
      febrile neutropenia, and bleeding tendency, which may result in falls and fall
      related injuries. MATERIALS AND METHODS: We retrospectively analyzed 397
      consecutive admissions to the hematology unit at our institute which included 201
      adult patients with hematologic disease. RESULTS AND CONCLUSIONS: A total of 56
      fall events were observed in 43 patients, and the incidence of falls was 2.49 per
      1000 person-days. The median hemoglobin, platelet, and serum albumin levels prior
      to fall events were 8.65g/dl (range, 6.3-12.7), 38*109/l (range, 7-454), and
      2.85g/dl (range, 1.6-4.3), respectively. Despite the presence of thrombocytopenia
      among the majority of patients who fell, no serious injury was observed. Multiple
      variable logistic regression analysis demonstrated that age older than 65years
      (hazard ratio [HR], 2.86; 95% confidence interval [CI], 1.17-6.99, P=0.02),
      admission for allo-HCT (HR, 9.48; 95% CI, 3.35-26.80, P<0.001), hypnotic
      medication (HR, 3.57; 95% CI, 1.56-8.20, P=0.002), urinary or intravenous
      catheter placement (HR, 2.34; 95% CI, 1.08-5.09, P=0.03), and hypoalbuminemia
      (HR, 2.30; 95% CI, 1.07-4.96, P=0.03) were significantly associated with
      increased fall risk. These findings indicated that special attention should be
      paid to patients with such risk factors during their treatment.

PMID- 28743507
TI  - Ketamine for Pain Management-Side Effects & Potential Adverse Events.
AB  - An old anesthetic agent, ketamine is finding new use in lower doses for analgesic
      purposes. There are concerns stemming from its potential side effects
      specifically psychomimetic effects. These side effects are directly related to
      dose amount. The doses used for analgesic purposes are much lower than those used
      for anesthesia purposes. A literature review was performed to ascertain potential
      side effects and/or adverse events when using ketamine for analgesia purposes.
      The search included CINAHL, PubMed, and Ovid using the search terms "ketamine,"
      "ketamine infusion," "pain," "adverse events," "practice guideline," and
      "randomized controlled trial." Searches were limited to full-text, peer-reviewed
      articles and systematic reviews. Initially 1,068 articles were retrieved. The
      search was then narrowed by using the Boolean connector AND with various search
      term combinations. After adjusting for duplication, article titles and abstracts
      were reviewed, leaving 25 articles for an in-depth analysis. Specific exclusion
      criteria were then applied. The literature supports the use of ketamine for
      analgesic purposes, and ketamine offers a nonopioid option for the management of
      some pain conditions. Because ketamine is still classified as an anesthetic
      agent, health care institutions should develop their own set of policies and
      protocols for the administration of ketamine. By using forethought and
      understanding of the properties of ketamine, appropriate care may be planned to
      mitigate potential side effects and adverse events so that patients are
      appropriately cared for and their pain effectively managed.

PMID- 28743508
TI  - Design, synthesis, docking and biological evaluation of 4-phenyl-thiazole
      derivatives as autotaxin (ATX) inhibitors.
AB  - The autotaxin-lysophophatidic acid (ATX-LPA) signaling pathway is involved in
      several human diseases such as cancer, autoimmune diseases, inflammatory diseases
      neurodegenerative diseases and fibrotic diseases. Herein, a series of 4-phenyl
      thiazole based compounds was designed and synthesized. Compounds were evaluated
      for their ATX inhibitory activity using FS-3 and human plasma assays. In the FS-3
      assay, compounds 20 and 21 significantly inhibited the ATX at low nanomolar level
      (IC50=2.99 and 2.19nM, respectively). Inhibitory activity of 21 was found to be
      slightly better than PF-8380 (IC50=2.80nM), which is one of the most potent ATX
      inhibitors reported till date. Furthermore, 21 displayed higher potency
      (IC50=14.99nM) than the first clinical ATX inhibitor, GLPG1690 (IC50=242.00nM) in
      the human plasma assay. Molecular docking studies were carried out to explore the
      binding pattern of newly synthesized compounds within active site of ATX. Docking
      studies suggested the putative binding mode of the novel compounds. Good ATX
      inhibitory activity of 21 was attributed to the hydrogen bonding interactions
      with Asn230, Trp275 and active site water molecules; electrostatic interaction
      with catalytic zinc ion and hydrophobic interactions with amino acids of the
      hydrophobic pocket.

PMID- 28743509
TI  - Synthesis and evaluation of modified chalcone based p53 stabilizing agents.
AB  - Tumor suppressor protein p53 induces cell cycle arrest and apoptotic cell death
      in response to various cellular stresses thereby preventing cancer development.
      Activation and stabilization of p53 through small organic molecules is,
      therefore, an attractive approach for the treatment of cancers retaining wild
      type p53. In this context, a series of nineteen chalcones with various
      substitution patterns of functional groups including chloro, fluoro, methoxy,
      nitro, benzyloxy, 4-methyl benzyloxy was prepared using Claisen-Schmidt
      condensation. The compounds were characterized using NMR, HRMS, IR and melting
      points. Evaluation of synthesized compounds against human colorectal (HCT116) and
      breast (CAL-51) cancer cell lines revealed potent antiproliferative activities.
      Nine compounds displayed GI50 values in the low micromolar to submicromolar
      range; for example (E)-1-phenyl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
      (SSE14108) showed GI50 of 0.473+/-0.043uM against HCT116 cells. Further analysis
      of these compounds revealed that (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one
      (SSE14105) and (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (SSE14106) caused
      rapid (4 and 8-h post-treatment) accumulation of p53 in HCT116 cells similar to
      its induction by positive control, Nutlin-3. Such activities were absent in 3-(4
      methoxyphenyl)propiophenone (SSE14106H2) demonstrating the importance of
      conjugated ketone for antiproliferative and p53 stabilizing activity of the
      chalcones. We further evaluated p53 levels in the presence of cycloheximide (CHX)
      and the results showed that the p53 stabilization was regulated at post
      translational level through blockage of its degradation. These chalcones can,
      therefore, act as fragment leads for further structure optimization to obtain
      more potent p53 stabilizing agents with enhanced anti-proliferative activities.

PMID- 28743510
TI  - Fiona Kenyon: Bringing Science to the Farm.

PMID- 28743511
TI  - Raf-1/CK2 and RhoA/ROCK signaling promote TNF-alpha-mediated endothelial
      apoptosis via regulating vimentin cytoskeleton.
AB  - Both RhoA/ROCK and Raf-1/CK2 pathway play essential roles in cell proliferation,
      apoptosis, differentiation, and multiple other common cellular functions. We
      previously reported that vimentin is responsible for TNF-alpha-induced cell
      apoptosis. Herein, we investigated the regulation of RhoA/ROCK and Raf-1/CK2
      signaling on vimentin filaments and endothelial apoptosis mediated by TNF-alpha.
      Treatment with TNF-alpha significantly induced the activation of RhoA and ROCK,
      and the expression of ROCK1. RhoA deficiency could obviously inhibit ROCK
      activation and ROCK1 expression induced by TNF-alpha. Both RhoA deficiency and
      ROCK activity inhibition (Y-27632) greatly inhibited endothelial apoptosis and
      preserved cell viability in TNF-alpha-induced human umbilical vein endothelial
      cells (HUVECs). Also vimentin phosphorylation and the remodeling of vimentin or
      phospho-vimentin induced by TNF-alpha were obviously attenuated by RhoA
      suppression and ROCK inhibition. TNF-alpha-mediated vimentin cleavage was
      significantly inhibited by RhoA suppression and ROCK inhibition through
      decreasing the activation of caspase3 and 8. Furthermore, TNF-alpha treatment
      greatly enhanced the activation of Raf-1. Suppression of Raf-1 or CK2 by its
      inhibitor (GW5074 or TBB) blocked vimentin phosphorylation, remodeling and
      endothelial apoptosis, and preserved cell viability in TNF-alpha-induced HUVECs.
      However, Raf-1 inhibition showed no significant effect on TNF-alpha-induced ROCK
      expression and activation, suggesting that the regulation of Raf-1/CK2 signaling
      on vimentin was independent of ROCK. Taken together, these results indicate that
      both RhoA/ROCK and Raf-1/CK2 pathway are responsible for TNF-alpha-mediated
      endothelial cytotoxicity via regulating vimentin cytoskeleton.

PMID- 28743512
TI  - Inferring transcription factor activity from microarray data reveals novel
      targets for toxicological investigations.
AB  - Transcription factors (TFs) are important modulators of the inducible portion of
      the transcriptome, and therefore relevant in the context of exposure to exogenous
      compounds. Current approaches to predict the activity of TFs in biological
      systems are usually restricted to a few entities at a time due to low-throughput
      techniques targeting a limited fraction of annotated human TFs. Therefore, high
      throughput alternatives may help to identify new targets of mechanistic and
      predictive value in toxicological investigations. In this study, we inferred the
      activity multiple TFs using publicly available microarray data from primary human
      hepatocytes exposed to hundreds of chemicals and evaluated these molecular
      profiles using multiple correspondence analysis. Our results demonstrate that the
      lowest dose and latest exposure time (24h) in a subset of chemicals generates a
      signature indicative of carcinogenicity possibly due to DNA-damaging properties.
      Furthermore, profiles from the earliest exposure time (2h) and highest dose
      creates clusters of chemicals implicated in the development of diverse forms of
      drug-induced liver injury (DILI). Both approaches yielded a number of TFs with
      similar activity across groups of chemicals, including TFs known in toxicological
      responses such as AhR, NFE2L2 (Nrf2), NF-kappaB and PPARG. FOXM1, IRF1 and E2F4
      were some of the TFs identified that may be relevant in genotoxic carcinogenesis.
      SMADs (SMAD1, SMAD2, SMAD5) and KLF5 were identified as some of potentially new
      TFs whose inferred activities were linked to acute and progressive outcomes in
      DILI. In conclusion this study offers a novel mechanistic approach targeting TF
      activity during chemical exposure.

PMID- 28743513
TI  - Chronic exposure to the fungicide propiconazole: Behavioral and reproductive
      evaluation of F1 and F2 generations of male rats.
AB  - Several studies have suggested that propiconazole (PROP) may be an endocrine
      disruptor; possibly altering the activity of the CYP51 enzyme, which is part of
      the cholesterol biosynthesis pathway required for the production of sexual
      steroid hormones. Another PROP effect is inhibition of the aromatase enzyme that
      converts androgens into estrogens, which could lead to negative effects on
      reproductive parameters. Therefore, the present study evaluated the reproductive
      and developmental toxicity of PROP by exposing two generations (F1 and F2) of
      male rats to this fungicide, since a previous study from our lab reported that
      PROP has anti-estrogenic and anti-androgenic activities (Costa et al., 2015) in
      the male parental (P) generation. The F1 males were exposed to PROP (4 or
      20mg/kg) through germ cells (via the P generation), intra uterus, and lactation,
      following treatment by gavage from post-natal day (PND) 21 to 120, while the F2
      generation was exposed through germ cells, intra uterus, and lactation. The
      parameters observed in both F1 and F2 generations were: body weight, anogenital
      distance (PND 0 and 21), ontogenic reflex, testosterone plasmatic levels, testis
      weight, and testicular histomorphology (PND 21); and in the F1 generation only:
      preputial separation (PND 40), sexual behavior, organ weights, testosterone and
      estradiol plasmatic levels (PND 120), sperm count and morphology, and testicular
      histomorphology at adulthood. In the F1 and F2 generations, PROP (4mg/kg)
      presented a decrease in testosterone levels, and in the F1 decreases in the vas
      deferens weight, without hormonal and functional changes of the reproductive
      organs, either at 4mg/kg or at 20mg/kg, in adulthood. Based on the results of
      this work, PROP did not alter the gonadal-endocrine parameters under these
      exposure conditions in rats.

PMID- 28743514
TI  - Precision cut lung slices as test system for candidate therapeutics in
      organophosphate poisoning.
AB  - Standard therapeutic options in organophosphate (OP) poisoning are limited to the
      administration of atropine and oximes, a regimen often lacking in efficacy and
      applicability. Treatment alternatives are needed, preferably covering a broad
      spectrum of OP intoxications. Although recent research yielded several promising
      compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh)
      receptor or bispyridinium non-oximes, these substances still need further
      evaluation, especially regarding effects on the potentially lethal respiratory
      symptoms of OP poisoning. Aim of this study was the development of an applicable
      and easy method to test the therapeutic efficiency of such substances. For this
      purpose, airway responsiveness in viable precision cut lung slices (PCLS) from
      rats was analysed. We showed that ACh-induced airway contractions were
      spontaneously reversible in non-poisoned PCLS, whereas in OP poisoned PCLS,
      contractions were irreversible. This effect could be antagonized by addition of
      the standard therapeutic atropine, thereby presenting a clear indication for
      treatment efficiency. Now, candidate therapeutic compounds can be evaluated,
      based on their ability to counteract the irreversible airway contraction in OP
      poisoned PCLS.

PMID- 28743515
TI  - The influence of systemic cryotherapy on selected hemodynamic parameters and the
      assessment of the safety of its use in patients with successfully treated
      hypertension.

PMID- 28743516
TI  - Corrigendum to "The Nuclear Hormone Receptor Nr2c1 (Tr2) is a critical regulator
      of early retina cell pattering" [Dev. Biol. 16 (2017) 30797-7].

PMID- 28743517
TI  - The sensitive period for auditory-vocal learning in the zebra finch: Consequences
      of limited-model availability and multiple-tutor paradigms on song imitation.
AB  - Male zebra finches, Taeniopygia guttata, acquire their song during a sensitive
      period for auditory-vocal learning by imitating conspecific birds. Laboratory
      studies have shown that the sensitive period for song acquisition covers a
      developmental phase lasting from 25 to 65days post hatch (dph); formation of
      auditory memory primarily occurs between 25 and 35dph. The duration of the
      sensitive period is, however, dependent upon model availability. If a tutor is
      not available early in development, birds will learn from an adult male
      introduced to their cage even after they reach 65dph. Birds who are exposed to a
      second tutor as late as 63dph can successfully adjust their song 'template' to
      learn a new song model. However, if second-tutor song exposure occurs after
      65dph, learning of a new tutor's song will not occur for most individuals. Here,
      we review the literature as well as novel studies from our own laboratory
      concerning sensitive periods for auditory memory formation in zebra finches;
      these behavioral studies indicate that there are developmental constraints on
      imitative learning in zebra finches.

PMID- 28743518
TI  - Nitric oxide (NO) inhibition of meiotic G2-M1 transition in Anabas testudineus
      oocytes: Participation of cAMP-dependent protein kinase (PKA) in regulation of
      intra-oocyte signaling events.
AB  - Nitric oxide (NO) regulation of ovarian function in mammals has been studied
      extensively. However, relatively less information is available on NO action on
      meiotic G2-M1 transition in teleost oocytes. In the present study using follicle
      enclosed oocytes of Anabas testudineus, NO regulation of intra-oocyte signaling
      events during meiotic G2-M1 transition were examined. Priming with NO donor,
      sodium nitroprusside (SNP) prevented 17alpha,20beta-dihydroxy-4-pregenen-3-one
      (17,20beta-P)-induced germinal vesicle break down (GVBD) in dose- and duration
      dependent manner. Impaired GVBD response in SNP-treated groups corroborated well
      with reduced p34Cdc2 (Thr161) phosphorylation. Immunoblot analysis revealed that
      congruent with elevated cAMP-dependent protein kinase (PKA) phosphorylation
      (activation), NO inhibition of meiotic maturation involves down regulation of
      Cdc25 activation, Mos synthesis and MAPK3/1 (ERK1/2) phosphorylation. However,
      priming with PKA inhibitor (H89) could reverse SNP attenuation of oocyte GVBD
      significantly. Collectively our results indicate that negative influence of NO on
      meiotic G2-M1 transition in perch oocytes might involve PKA activation.

PMID- 28743519
TI  - The molecular complexity of primary ovarian insufficiency aetiology and the use
      of massively parallel sequencing.
AB  - Primary ovarian insufficiency (POI) is a frequently occurring pathology, leading
      to infertility. Genetic anomalies have been described in POI and mutations in
      numerous genes have been definitively related to the pathogenesis of the disease.
      Some studies based on next generation sequencing (NGS) have been successfully
      undertaken as they have led to identify new mutations associated with POI
      aetiology. The purpose of this review is to present the most relevant molecules
      involved in diverse complex pathways, which may contribute towards POI. The main
      genes participating in bipotential gonad formation, sex determination, meiosis,
      folliculogenesis and ovulation are described to enable understanding how they may
      be considered putative candidates involved in POI. Considerations regarding NGS
      technical aspects such as design and data interpretation are mentioned.
      Successful NGS initiatives used for POI studying and future challenges are also
      discussed.

PMID- 28743520
TI  - Atherosclerosis and inflammation. Clinical aspects of a modern tale.

PMID- 28743521
TI  - Corrigendum to "Non-invasive tracking of hydrogel degradation using upconversion
      nanoparticles" [Acta Biomater. 55 (2017) 410-419].

PMID- 28743522
TI  - RIFM fragrance ingredient safety assessment, terpineol, CAS Registry Number 8000
      41-7.

PMID- 28743523
TI  - RIFM fragrance ingredient safety assessment, 3,7-dimethyl-1-octanol, CAS Registry
      Number 106-21-8.

PMID- 28743524
TI  - RIFM fragrance ingredient safety assessment, 4-Carvomenthenol, CAS Registry
      Number 562-74-3.

PMID- 28743525
TI  - RIFM fragrance ingredient safety assessment, isobutyl N-methylanthranilate, CAS
      Registry Number 65505-24-0.

PMID- 28743526
TI  - Change in Prostate Specific Antigen Concentration in Men with Prostate Specific
      Antigen Less than 2.5 ng/ml Taking Low Dose Finasteride or Dutasteride for Male
      Androgenetic Alopecia.
AB  - PURPOSE: In this retrospective cohort study we assessed the effect on prostate
      specific antigen concentration of low dose finasteride or dutasteride treatment
      for male androgenetic alopecia in men with baseline serum prostate specific
      antigen less than 2.5 ng/ml. MATERIALS AND METHODS: The cohort consisted of 1,379
      consecutive male patients who were treated for androgenetic alopecia with
      finasteride 1.25 mg daily or dutasteride 0.5 mg every 3 days in 2002 to 2012 and
      who underwent prostate specific antigen measurements at baseline and at least
      once thereafter. Patients in whom baseline or followup prostate specific antigen
      after prescription exceeded 2.5 ng/ml were excluded from study to rule out men
      with a higher likelihood of prostate cancer. Patients were stratified according
      to age, baseline prostate specific antigen, medication type and treatment
      duration. RESULTS: Overall low dose 5alpha-reductase inhibitor treatment reduced
      prostate specific antigen by 27.8% relative to baseline. Of the patients 1,094
      (79.3%) showed prostate specific antigen decreases (average 40.8%). In the
      remaining 285 patients (20.7%) prostate specific antigen was stable or increased
      (average 24.2% increase). Closer analysis largely showed that only men with
      baseline prostate specific antigen 0.5 ng/ml or greater had a treatment related
      prostate specific antigen reduction. On multivariate logistic analysis low
      baseline prostate specific antigen was significantly associated with
      stable/increased prostate specific antigen. Low dose dutasteride and finasteride
      reduced prostate specific antigen to similar degrees (31.1% and 25.1%,
      respectively). A marked prostate specific antigen decrease of 26.0% was observed
      even after short-term treatment (3 to 6 months). CONCLUSIONS: Dutasteride and
      finasteride reduced prostate specific antigen to similar degrees. This effect was
      observed soon after commencing treatment. In patients with low baseline prostate
      specific antigen the levels could remain stable or even increase. These findings
      are limited to men with baseline prostate specific antigen less than 2.5 ng/ml.

PMID- 28743527
TI  - Effectiveness and Complications of Augmentation Cystoplasty with or without
      Nonrefluxing Ureteral Reimplantation in Patients with Bladder Dysfunction: A
      Single Center 11-Year Experience.
AB  - PURPOSE: We reviewed our experience with the effectiveness and complications of
      augmentation cystoplasty with or without nonrefluxing ureteral reimplantation in
      adult patients with long-standing bladder dysfunction. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 173 patients who underwent augmentation
      cystoplasty with or without ureteral reimplantation at our center from July 2005
      to July 2016. Clinical data, and magnetic resonance urography and videourodynamic
      parameters were collected. Upper urinary tract dilatation and vesicoureteral
      reflux grading systems were used to evaluate upper urinary tract function.
      Postoperative complications were evaluated. RESULTS: Ureteral reimplantation was
      performed in 160 patients (266 ureteral units) and 120 ureteral units were
      simultaneously managed by tailoring and/or ureterolysis. Mean followup was 44.4
      months (range 3 to 108). Mean maximum bladder capacity and bladder compliance
      significantly increased (p <0.0001), and maximum detrusor pressure and serum
      creatinine decreased compared with preoperative levels (p <0.05). Upper urinary
      tract dilatation and vesicoureteral reflux significantly improved after surgery.
      Postoperative complications included persistent vesicoureteral reflux in 1
      patient (0.6%), anastomotic stricture in 14 ureteral units (5.3%), bowel
      dysfunction in 11 patients (6.4%), a need for laparotomy in 4 (2.3%), urinary
      tract stone in 15 (8.7%) and deteriorating renal function in 9 (5.2%).
      CONCLUSIONS: This retrospective study indicates that ureteral reimplantation
      concomitant with augmentation cystoplasty may be beneficial in patients with low
      pressure or high grade vesicoureteral reflux, ureterovesical junction obstruction
      or ureteral tortuosity, and adhesions and/or severe upper urinary tract
      dilatation, especially in those with a long medical history.

PMID- 28743528
TI  - Contrast Enhanced Ultrasound as a Radiation-Free Alternative to Fluoroscopic
      Nephrostogram for Evaluating Ureteral Patency.
AB  - PURPOSE: We compared contrast enhanced ultrasound and fluoroscopic
      nephrostography in the evaluation of ureteral patency following percutaneous
      nephrolithotomy. MATERIALS AND METHODS: This prospective cohort, noninferiority
      study was performed after obtaining institutional review board approval. We
      enrolled eligible patients with kidney and proximal ureteral stones who underwent
      percutaneous nephrolithotomy at our center. On postoperative day 1 patients
      received contrast enhanced ultrasound and fluoroscopic nephrostogram within 2
      hours of each other to evaluate ureteral patency, which was the primary outcome
      of this study. RESULTS: A total of 92 pairs of imaging studies were performed in
      82 patients during the study period. Five study pairs were excluded due to
      technical errors that prevented imaging interpretation. Females slightly
      predominated over males with a mean +/- SD age of 50.5 +/- 15.9 years and a mean
      body mass index of 29.6 +/- 8.6 kg/m2. Of the remaining 87 sets of studies 69
      (79.3%) demonstrated concordant findings regarding ureteral patency for the 2
      imaging techniques and 18 (20.7%) were discordant. The nephrostomy tube was
      removed on the same day in 15 of the 17 patients who demonstrated antegrade urine
      flow only on contrast enhanced ultrasound and they had no subsequent adverse
      events. No adverse events were noted related to ultrasound contrast injection.
      While contrast enhanced ultrasound used no ionizing radiation, fluoroscopic
      nephrostograms provided a mean radiation exposure dose of 2.8 +/- 3.7 mGy.
      CONCLUSIONS: A contrast enhanced ultrasound nephrostogram can be safely performed
      to evaluate for ureteral patency following percutaneous nephrolithotomy. This
      imaging technique was mostly concordant with fluoroscopic findings. Most
      discordance was likely attributable to the higher sensitivity for patency of
      contrast enhanced ultrasound compared to fluoroscopy.

PMID- 28743529
TI  - Implementation of a Patient Navigator Program to Reduce 30-day Heart Failure
      Readmission Rate.
AB  - With increasing awareness to provide personalized care our institution applied
      the American College of Cardiology (ACC) Patient Navigator Program to identify
      hospitalized heart failure (HF) patients and improve transitions and outcomes.
      Utilizing a Navigator Team (NT) composed of a nurse and clinical pharmacist, we
      delivered evidenced-based interventions and hypothesized this approach would
      improve identification of HF inpatients and reduce the 30-day all-cause
      readmission rate. Patients were followed from admission to discharge and received
      at least one intervention, tailored to the patient's health literacy and social
      needs. The 30-day all-cause readmission rate was 17.6% for the Patient Navigator
      Program and 25.6% for the medical center. Compared to the medical center there
      was a statistically significant increase in education and follow-up. For patients
      who received specific NT interventions of education and follow-up the readmission
      rate was 10.3% and 6.1% respectively. Hospital programs can easily embed a NT
      into existing initiatives to further reduce the readmission rate.

PMID- 28743530
TI  - Different inhibitory potential of sex hormones on NNK detoxification in vitro: A
      possible explanation for gender-specific lung cancer risk.
AB  - Smoking women are probably at a higher risk to develop lung cancer than men.
      Different explanations exist for these findings, a gender-specific impairment of
      tobacco carcinogen metabolism being one of them. In this study, we examined the
      inhibition of NNK reduction to NNAL, the first and most important detoxication
      step of this tobacco-specific carcinogen. It is mediated by different carbonyl
      reductases of the SDR (CBR1 and 11betaHSD1) and AKR (AKR1B10, AKR1C1, AKR1C2 and
      AKR1C4) superfamilies. Inhibition constants of NNK reduction were determined with
      male (testosterone) and female (estradiol, progesterone) sex hormones and the
      contraceptives ethinylestradiol and drospirenone in A549 cells and with purified
      enzymes. Female sex hormones turned out to be stronger inhibitors than
      testosterone. The gestagen progesterone and its synthetic derivative drospirenone
      are the strongest inhibitors with Ki-values similar to hormone levels in pregnant
      women or women using hormonal contraceptives. Therefore, pregnancy or hormonal
      contraception may commit these women as high risk groups. The results of this
      study support the hypothesis that women bear a higher lung cancer risk when
      smoking because of female sex hormones acting as inhibitors of NNK detoxication.

PMID- 28743531
TI  - Metabolic regulation of glioma stem-like cells in the tumor micro-environment.
AB  - Cancer metabolism has emerged as one of the most interesting old ideas being
      revisited from a new perspective. In the early 20th century Otto Warburg declared
      metabolism the prime cause in a disease of many secondary causes, and this
      statement seems more prescient in view of modern expositions into the true nature
      of tumor evolution. As the complexity of tumor heterogeneity becomes more clear
      from a genetic perspective, it is important to consider the inevitably
      heterogeneous metabolic components of the tumor and the tumor microenvironment.
      High grade gliomas remain one of the most difficult to treat solid tumors, due in
      part to the highly vascularized nature of the tumor and the maintenance of more
      resistant stem-like subpopulations within the tumor. Maintenance of glioma stem
      cells (GSCs) requires specific alterations within the cells and the greater tumor
      microenvironment with regards to signaling and metabolism. Specific niches within
      gliomas help foster the survival of stem-like sub-populations of cells with high
      tumorigenicity and high metabolic plasticity. Understanding these maintenance
      pathways and the metabolic dependencies within the niche may highlight potential
      avenues of addressing tumor resistance and recurrence in glioma patients.

PMID- 28743532
TI  - A synthetic peptide hijacks the catalytic subunit of class I PI3K to suppress the
      growth of cancer cells.
AB  - Activation of class I Phosphoinositide 3-kinases (PI3Ks) by mutation or
      overexpression closely correlates with the development of various human cancers.
      Class I PI3Ks are heterodimers composed of p110 catalytic subunits and regulatory
      subunits represented by p85. PAQR3 has been found to inhibit p110alpha activity
      by blocking its interaction with p85. In this study, we identified the N-terminal
      6-55 amino acid residues of PAQR3 being sufficient for its interaction with
      p110alpha. A synthetic peptide, P6-55, that contains the N-terminus of PAQR3
      could disrupt the interactions of p110alpha with both PAQR3 and p85. The activity
      of PI3K was also inhibited by P6-55, accompanied by significant inhibition of
      cancer cell proliferation. In a xenograft mouse model, P6-55 was able to reduce
      tumor growth in vivo. Furthermore, P6-55 was capable of inhibiting the elevated
      basal PI3K activity of H1047R, a hotspot mutation found in many types of human
      cancers. The cell proliferation and migration of cancer cells bearing H1047R
      mutation were also reduced by P6-55. In conclusion, our study provides a proof of
      concept that blocking the interaction of p110alpha with p85 by a peptide can
      serve as a new strategy to inhibit the oncogenic activity of PI3K in cancer
      therapy.

PMID- 28743533
TI  - Should non-bacteraemic patients with a colonized catheter receive antimicrobial
      therapy?
AB  - OBJECTIVES: The impact of antimicrobial therapy on the outcomes of patients with
      colonized catheters and no bacteraemia has not been assessed. This study assessed
      whether targeted antibiotic therapy is related to a poor outcome in patients with
      positive cultures of blood drawn through a non-tunnelled central venous catheter
      (CVC) and without concomitant bacteraemia. METHODS: This was a retrospective
      study involving adult patients with positive blood cultures drawn through a CVC
      and negative peripheral vein blood cultures. Patients were classified into two
      groups: those with clinical improvement and those with a poor outcome. These two
      groups were compared. The outcome was considered poor in the presence of one or
      more of the following: death, bacteraemia or other infection due to the same
      microorganism, and evidence of catheter-related bloodstream infection. RESULTS: A
      total of 100 patients were included (31 with a poor outcome). The only
      independent predictors of a poor outcome were a McCabe and Jackson score of 1-2
      and a median APACHE score of 5. No association was found between the use of
      targeted antimicrobial therapy and a poor outcome when its effect was adjusted
      for the rest of the variables. CONCLUSIONS: This study showed that antimicrobial
      therapy was not associated with a poor outcome in non-bacteraemic patients with
      positive blood cultures drawn through a CVC.

PMID- 28743534
TI  - Complementary uses of small angle X-ray scattering and X-ray crystallography.
AB  - Most proteins function within networks and, therefore, protein interactions are
      central to protein function. Although stable macromolecular machines have been
      extensively studied, dynamic protein interactions remain poorly understood. Small
      angle X-ray scattering probes the size, shape and dynamics of proteins in
      solution at low resolution and can be used to study samples in a large range of
      molecular weights. Therefore, it has emerged as a powerful technique to study the
      structure and dynamics of biomolecular systems and bridge fragmented information
      obtained using high-resolution techniques. Here we review how small-angle X-ray
      scattering can be combined with other structural biology techniques to study
      protein dynamics. This article is part of a Special Issue entitled: Biophysics in
      Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman.

PMID- 28743535
TI  - Discharge on the day of birth, parental response and health and schooling
      outcomes.
AB  - Exploiting the Danish roll-out of same-day discharge policies after uncomplicated
      births, we find that treated newborns have a higher probability of hospital
      readmission in the first month after birth. While these short-run effects may
      indicate substitution of hospital stays with readmissions, we also find that-in
      the longer run-a same-day discharge decreases children's 9th grade GPA. This
      effect is driven by children and mothers, who prior to the policy change would
      have been least likely to experience a same-day discharge. Using administrative
      and survey data to assess potential mechanisms, we show that a same-day discharge
      impacts those parents' health investments and their children's medium-run health.
      Our findings point to important negative effects of policies that expand same-day
      discharge policies to broad populations of mothers and children.

PMID- 28743536
TI  - Vitamin panacea: Is advertising fueling demand for products with uncertain
      scientific benefit?
AB  - This study examines the effect of advertising on demand for vitamins-products
      with spiraling sales despite little evidence of efficacy. We merge seven years
      (2003-2009) of advertising data from Kantar Media with the Simmons National
      Consumer Survey to estimate individual-level vitamin print and television ad
      exposure effects. Identification relies on exploiting exogenous variation in year
      to-year advertising exposure by controlling for each individual's unique media
      consumption. We find that increasing advertising exposure from zero to the mean
      number of ads increases the probability of consumption by 1.2 and 0.8% points (or
      2 and 1.4%) in print and television respectively. Stratifications by the presence
      of health conditions suggests that in print demand is being driven by both
      healthy and sick individuals.

PMID- 28743537
TI  - The expanding role of sphingolipids in lipid droplet biogenesis.
AB  - Sphingolipids are a diverse class of lipids that have regulatory, structural, and
      metabolic functions. Although chemically distinct from the neutral lipids and the
      glycerophospholipids, which are the main lipid components of the lipid droplets,
      sphingolipids have nonetheless been shown to influence lipid droplet formation.
      The goal of this article is to review the available information and provide a
      cohesive picture of the role sphingolipids play in lipid droplet biogenesis. The
      following topics are discussed: (i) the abundance of sphingolipids in lipid
      droplets and their functional significance; (ii) cross-talk between the synthetic
      pathways of sphingolipids, glycerophospholipids, and neutral lipids; (iii) the
      impact of bioactive sphingolipids on TAG synthesis and degradation; (iv)
      interactions between sphingolipids and other lipid droplet components, like
      cholesterol esters and proteins; (v) inhibition/genetic deletion of specific
      sphingolipid metabolic enzymes and the resulting effects on lipid droplet
      formation in mouse models. This article is part of a Special Issue entitled:
      Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs
      Hesselink.

PMID- 28743538
TI  - Protein-losing enteropathy resolved after ventral abdominal hernia repair.

PMID- 28743539
TI  - Recommendations of everolimus use in liver transplant.
AB  - Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus
      are immunosuppressive agents with a minor nephrotoxic effect, limited to the
      development of proteinuria in some cases. The combination of EVL and low-dose
      tacrolimus has proven to be as safe and effective as standard therapy with
      tacrolimus for the prevention of acute cellular rejection. Early initiation of
      EVL-based immunosuppressive regimens with reduced exposure to calcineurin
      inhibitors has been shown to significantly improve renal function of LT
      recipients during induction and maintenance phases, with comparable efficacy and
      safety profiles. In patients with established kidney failure, initiating EVL may
      enable clinicians to reduce calcineurin inhibitors exposure, thereby contributing
      to the improved renal function of these patients. Although there is not
      sufficient evidence to recommend their use to prevent the recurrence of
      hepatocellular carcinoma and the progression of de novo tumours, they are used in
      this context in routine clinical practice.

PMID- 28743540
TI  - Limitations of the Mycobacterium tuberculosis reference genome H37Rv in the
      detection of virulence-related loci.
AB  - The genome sequence of Mycobacterium tuberculosis strain H37Rv is an important
      and valuable reference point in the study of M. tuberculosis phylogeny, molecular
      epidemiology, and drug-resistance mutations. However, it is becoming apparent
      that use of H37Rv as a sole reference genome in analysing clinical isolates
      presents some limitations to fully investigating M. tuberculosis virulence. Here,
      we examine the presence of single locus variants and the absence of entire genes
      in H37Rv with respect to strains that are responsible for cases and outbreaks of
      tuberculosis. We discuss how these polymorphisms may affect phenotypic properties
      of H37Rv including pathogenicity. Based on our observations and those of other
      researchers, we propose that use of a single reference genome, H37Rv, is not
      sufficient for the detection and characterisation of M. tuberculosis virulence
      related loci. We recommend incorporation of genome sequences of other reference
      strains, in particular, direct clinical isolates, in such analyses in addition to
      H37Rv.

PMID- 28743541
TI  - A comparative characterization of estrogens used in hormone therapy via estrogen
      receptor (ER)-alpha and -beta.
AB  - Conventional hormone therapy (HT) containing estrogens such as ethinylestradiol
      (EE) have been associated with an increased risk of breast cancer and
      cardiovascular disease resulting in women seeking safer alternatives that are
      claimed to have fewer health risks. One such alternative gaining popularity, is
      custom-compounded bioidentical (b)HT formulations containing bioidentical
      estradiol (bE2) and estriol (bE3). However, the preparation of these custom
      compounded estrogens is not regulated, and depending on the route of synthesis,
      steroid mixtures with differing activities may be produced. Thus, an
      investigation into the activities of estrogens prepared by custom-compounded
      pharmacies is warranted. The aim of this study was therefore to directly compare
      the pharmacological properties of bE2 and bE3 of unknown purity relative to
      commercially available, pure E2, E3 and estrone (E1) standards as well as
      synthetic EE used in conventional HT via the human estrogen receptor (ER)-alpha
      and -beta. We determined precise equilibrium dissociation constants (Kd or Ki
      values) and showed that bE2 and bE3 display similar binding affinities to the E2
      and E3 standards, while EE had a higher affinity for ERalpha, and E1 a lower
      affinity for ERbeta. Furthermore, all the estrogens display similar agonist
      efficacies, but not potencies, for transactivation on a minimal ERE-containing
      promoter via the individual ER subtypes. Although E2 and E3 were equally
      efficacious and potent on the endogenous ERE-containing pS2 promoter in the MCF-7
      BUS breast cancer cell line co-expressing ERalpha and ERbeta, E1 was less
      efficacious and potent than E2. This study is the first to demonstrate that the
      bioidentical estrogens, commercially available estrogen standards and synthetic
      EE are full agonists for transrepression on both minimal and endogenous NFkappaB
      containing promoters. Moreover, we showed that these estrogens all increase
      proliferation and anchorage-independent growth of MCF-7 BUS cells to a similar
      extent, suggesting that custom-compounded bHT may in fact not be a safer
      alternative to conventional HT. Furthermore, our results showing that E3 and E1
      are not weak estrogens, and that E3 does not antagonize the activity of E2,
      suggest that the rationale behind the use of E3 and E1 in custom-compounded bHT
      formulations should be readdressed. Taken together, the results indicating that
      there is mostly no difference between the custom-compounded bioidentical
      estrogens, commercially available estrogen standards and synthetic EE, at
      concentrations reflecting serum levels in women using estrogen-containing HT,
      suggest that there is no clear advantage in choosing bHT above conventional HT.

PMID- 28743542
TI  - The endocannabinoid system expression in the female reproductive tract is
      modulated by estrogen.
AB  - The endocannabinoid system (ECS) is involved in several physiological events that
      resulted in a growing interest in its modulation. Moreover, the uterine levels of
      anandamide (AEA), the major endocannabinoid, must be tightly regulated to create
      proper embryo implantation conditions. However, there are no evidences about the
      regulation of AEA in uterus by estrogen. Thus, the aim of this study is to
      elucidate whether estradiol benzoate (EB) and tamoxifen (TAM) administration to
      ovariectomized (OVX) rats can induce changes in the expression of cannabinoid
      receptors and AEA-metabolic enzymes in uterus by evaluating gene transcription
      and protein levels by qPCR, Western blot and immunohistochemistry. Moreover, the
      plasmatic and uterine levels of AEA and of prostaglandin E2 (PGE2) and
      prostaglandin F2alpha (PGF2alpha), the major cyclooxygenase-2 (COX-2) products,
      were determined by UPLC-MS/MS. The immunohistochemistry showed that cannabinoid
      receptors, as well as AEA-metabolic enzymes are mainly located in the epithelial
      cells of both lumen and glands and, to a lesser extent, in the muscle cells.
      Moreover, EB administration to OVX rats significantly increased CB1, CB2, NAPE
      PLD, FAAH and COX-2 expression and transcription. These effects were absent in
      TAM and TAM+EB treatments showing that this response is estrogen receptor
      dependent. Additionally, although uterine levels of AEA remained unchanged in EB
      or TAM treated animals, they showed a rise with EB treatment in plasma. The
      latter also produced a decrease in uterine PGE2 levels. In summary, these data
      collectively indicate that the expression of ECS components, as well as, the AEA
      and PGE2 levels in rat uterus is modulated by EB. Thus, estradiol may have a
      direct regulatory role in the modulation of ECS in female reproductive tissues.

PMID- 28743543
TI  - A recurrent synonymous mutation in the human androgen receptor gene causing
      complete androgen insensitivity syndrome.
AB  - Androgen insensitivity syndrome (AIS) is the most common cause of 46,XY disorders
      of sex development (46,XY DSD). This syndrome is an X-linked inheritance disease
      and it is caused by mutations in the human androgen receptor (AR) gene. Non
      synonymous point AR mutations are frequently described in this disease, including
      in the complete phenotype. We present a novel synonymous mutation in the human AR
      gene (c.1530C > T) in four 46,XY patients from two unrelated families associated
      with complete androgen insensitivity syndrome (CAIS). The analysis of mRNA from
      testis showed that synonymous AR mutation changed the natural exon 1 donor splice
      site, with deletion of the last 92 nucleotides of the AR exon 1 leading to a
      premature stop codon 12 positions ahead resulting in a truncate AR protein.
      Linkage analyses suggested a probable founder effect for this mutation. In
      conclusion, we described the first synonymous AR mutation associated with CAIS
      phenotype, reinforcing the disease-causing role of synonymous mutations.

PMID- 28743544
TI  - Sodium-dependent organic anion transporter (Slc10a6-/-) knockout mice show normal
      spermatogenesis and reproduction, but elevated serum levels for cholesterol
      sulfate.
AB  - The sodium-dependent organic anion transporter SOAT (gene name SLC10A6 in man and
      Slc10a6 in mice) is a plasma membrane transporter for sulfated steroids, which is
      highly expressed in germ cells of the testis. SOAT can transport biologically
      inactive sulfated steroids into specific target cells, where they can be
      reactivated by the steroid sulfatase (STS) to biologically active, unconjugated
      steroids known to regulate spermatogenesis. Significantly reduced SOAT mRNA
      expression was previously found in different forms of impaired spermatogenesis in
      man. It was supposed that SOAT plays a role for the local supply of steroids in
      the testis and consequently for spermatogenesis and fertility. Thus, an Slc10a6-/
      Soat knockout mouse model was established by recombination-based target deletion
      of the Slc10a6 gene to elucidate the role of Soat in reproduction. However, the
      Slc10a6-/- knockout mice were fertile, produced normal litter sizes, and had
      normal spermatogenesis and sperm vitality. This phenotype suggests that the loss
      of Soat can be compensated in the knockout mice or that Soat function is not
      essential for reproduction. In addition to reproductive phenotyping, a
      comprehensive targeted steroid analysis including a set of 9 un-conjugated and 12
      sulfo-conjugated steroids was performed in serum of Slc10a6-/- knockout and
      Slc10a6+/+ wildtype mice. Only cholesterol sulfate, corticosterone, and
      testosterone (only in the males) could be detected in considerable amounts.
      Interestingly, male Slc10a6-/- knockout mice showed significantly higher serum
      levels for cholesterol sulfate compared to their wildtype controls. As
      cholesterol sulfate has a broader impact apart from the testis, further analysis
      of this phenotype will include other organs such as skin and lung, which also
      show high Soat expression in the mouse.

PMID- 28743545
TI  - Maternal pneumococcal nasopharyngeal carriage and risk factors for neonatal
      carriage after the introduction of pneumococcal conjugate vaccines in The Gambia.
AB  - OBJECTIVES: Pneumococcal nasopharyngeal carriage occurs early in life. However,
      the role of vertical transmission is not well understood. The aims of this study
      were to describe carriage among mothers and their newborns, and to assess for
      risk factors for neonatal carriage. METHODS: In a nested retrospective cohort
      study, we analysed data from the control arm of a randomized controlled trial
      conducted in The Gambia 2 to 3 years after introduction of pneumococcal conjugate
      vaccine (PCV) 13. Nasopharyngeal swabs were collected from 374 women and their
      newborns on the day of delivery, then 3, 6, 14 and 28 days later. Pneumococci
      were isolated and serotyped using conventional microbiologic methods. RESULTS:
      Carriage increased from 0.3% (1/373) at birth to 37.2% (139/374) at day 28 (p
      <0.001) among neonates and from 17.1% (64/374) to 24.3% (91/374) (p 0.015) among
      women. In both groups, PCV13 vaccine-type (VT) serotypes accounted for
      approximately one-third of the pneumococcal isolates, with serotype 19A being the
      most common VT. Maternal carriage (adjusted odds ratio (OR) = 2.82; 95%
      confidence interval (CI), 1.77-4.80), living with other children in the household
      (adjusted OR = 4.06; 95% CI, 1.90-8.86) and dry season (OR = 1.98; 95% CI, 1.15
      3.43) were risk factors for neonatal carriage. Over half (62.6%) of the neonatal
      carriage was attributable to living with other children in the same household.
      CONCLUSIONS: Three years after the introduction of PCV in The Gambia, newborns
      are still rapidly colonized with pneumococcus, including PCV13 VT. Current
      strategies for pneumococcal control in Africa do not protect this age group
      beyond the herd effect.

PMID- 28743546
TI  - Human and animal leptospirosis in Southern Brazil: A five-year retrospective
      study.
AB  - BACKGROUND: Leptospirosis is an emerging zoonosis attributed to multiple
      reservoirs. Climatic conditions influence the transmission of pathogenic
      leptospires, which require warm and humid conditions for survival. The influence
      of seasonality in human and animal leptospirosis in the subtropical region of
      Brazil remains poorly understood. METHODS: We performed a retrospective study to
      describe the patterns of human and animal exposure to leptospirosis and their
      association with precipitation events in Southern Brazil. Rainfall data were
      obtained from satellite images. Serum samples were tested using the microscopic
      agglutination test (MAT); samples with titer >= 100 were defined as seroreactive.
      Linear regression and Pearson's correlation were performed to assess whether
      there is a relationship between these variables. RESULTS: We found that
      precipitation events were not significantly associated with the exposure to
      leptospirosis in humans or animal species, except for dogs. The interspecies
      analysis revealed an association between canine and human exposure to
      leptospirosis. Leptospira kirschneri serovar Butembo (serogroup Autumnalis)
      presented the highest seroreactivity in humans. CONCLUSION: This study provides
      valuable insights in human and animal leptospirosis in Southern Brazil. These
      insights will be essential to design intervention measures directed to reduce
      disease dissemination.

PMID- 28743547
TI  - Early processing of orthographic language membership information in bilingual
      visual word recognition: Evidence from ERPs.
AB  - For successful language comprehension, bilinguals often must exert top-down
      control to access and select lexical representations within a single language.
      These control processes may critically depend on identification of the language
      to which a word belongs, but it is currently unclear when different sources of
      such language membership information become available during word recognition. In
      the present study, we used event-related potentials to investigate the time
      course of influence of orthographic language membership cues. Using an oddball
      detection paradigm, we observed early neural effects of orthographic bias
      (Spanish vs. English orthography) that preceded effects of lexicality (word vs.
      pseudoword). This early orthographic pop-out effect was observed for both words
      and pseudowords, suggesting that this cue is available prior to full lexical
      access. We discuss the role of orthographic bias for models of bilingual word
      recognition and its potential role in the suppression of nontarget lexical
      information.

PMID- 28743548
TI  - Identifying barriers to early mobilisation among mechanically ventilated patients
      in a trauma intensive care unit.
AB  - : Mechanically ventilated patients can be at risk for functional decline (Cameron
      et al., 2015). Early mobilisation of mechanically ventilated patients can improve
      outcomes after critical illness to prevent this decline. Although registered
      nurses understand the importance of early mobilisation there are nurses who are
      unwilling to mobilise patients. AIM: The aim of this study is to examine whether
      nurses' attitudes and beliefs are barriers for early mobilisation and evaluate
      whether an education intervention can improve early mobilisation. METHOD: Pre
      test, post-test intervention with registered nurses and charge nurses in a 22 bed
      trauma intensive care setting. PROCEDURE: Pre-test, post-test survey assessed
      perceived barriers in knowledge, attitudes, and behaviours followed by targeted
      education. RESULTS: Dependent Sample T-test revealed a statistically significant
      increase in post-test responses for the subscales knowledge, attitudes, and
      behaviours with early mobilisation. This over-all increase in post-test results
      support that understanding barriers can improve patient outcomes. CONCLUSION: Use
      of structured surveys to identify barriers for early mobilisation among nursing
      can assist in providing targeted education that address nurse's perception. The
      education intervention appeared to have a positive impact on attitudes but it is
      unknown if the difference was sustained over time or affected participants
      practice or patient outcomes.

PMID- 28743549
TI  - Pyruvate kinase M1 interacts with A-Raf and inhibits endoplasmic reticulum stress
      induced apoptosis by activating MEK1/ERK pathway in mouse insulinoma cells.
AB  - Apoptotic death of pancreatic beta cells is a major cause of type 2 diabetes
      mellitus (T2D) progression. Two isoforms of pyruvate kinase, PKM1 and PKM2, have
      been reported to participate in cell death in several cell types; however, little
      is known about their causal pathways in pancreatic beta-cell death. We examined
      whether the suppression of PKM1 or PKM2 affects endoplasmic reticulum (ER) stress
      induced apoptosis in a pancreatic beta-cell line, MIN6, and Beta-TC-6 and found
      that knockdown of PKM1, but not of PKM2, leads to the induction of ER stress
      induced apoptosis in these cells. We also investigated the mechanism by which
      PKM1 inhibits ER stress-induced apoptosis. We confirmed that PKM1 interacts with
      A-Raf, an upstream regulator of the MEK/ERK pathway, and that this interaction
      contributes to MEK1 phosphorylation by A-Raf. PKM1 knockdown suppresses the
      phosphorylation of MEK, ERK, and caspase-9 (Thr125), which is phosphorylated by
      the MEK/ERK pathway, thereby inhibiting the cleavage and activation of caspase-9.
      Thus, PKM1 knockdown activates the caspase-9/caspase-3 pathway under ER stress
      conditions and leads to apoptosis.

PMID- 28743550
TI  - Variable-focus microscopy and UV surface dissolution imaging as complementary
      techniques in intrinsic dissolution rate determination.
AB  - This work reports a novel approach to the assessment of the surface properties of
      compacts used in Surface Dissolution Imaging (SDI). SDI is useful for determining
      intrinsic dissolution rate (IDR), an important parameter in early stage drug
      development. Surface topography, post-compaction and post-SDI run, have been
      measured using a non-contact, optical, three-dimensional microscope based on
      focus variation, the Alicona Infinite Focus Microscope, with the aim of
      correlating the IDRs to the surface properties. Ibuprofen (IBU) was used as a
      model poorly-soluble drug. DSC and XRD were used to monitor possible polymorphic
      changes that may have occurred post-compaction and post-SDI run. IBUs IDR
      decreased from 0.033mg/min/cm2 to 0.022mg/min/cm2 from 10 to 20min, respectively,
      during the experiment. XRD and DSC showed no form changes during the SDI run. The
      surface topography images showed that a distinct imprint was embossed on the
      surfaces of some compacts which could affect IDRs. Surface parameter values were
      associated with the SDI experiments which showed strong correlations with the IDR
      values. The variable-focus microscope can be used as a complimentary tool in the
      determination of IDR values from the SDI.

PMID- 28743551
TI  - Solubilizing steroidal drugs by beta-cyclodextrin derivatives.
AB  - Administration of steroidal drugs is hampered by their very low solubilities in
      water. beta-Cyclodextrin and beta-cyclodextrin derivatives can solubilize
      steroids and improve bio-availability of these hydrophobic APIs. A systematic
      overview of the achievable solubility enhancements of various steroids,
      testosterone, estradiol, progesterone, hydrocortisone, prednisone, dexamethasone,
      and finasteride, is provided. Beside the spatial fit of the steroid within the
      cyclodextrin cavity also hydrophilic substituents at the cyclodextrin framework
      play an important role in the extent of solubilization observed. Uniformly
      substituted anionic heptakis-6-sulfoethylsulfanyl-6-deoxy-beta-cyclodextrin
      (HSES) performed best, reaching complexation efficiencies of 60-90mol% for most
      steroids. Two neutral beta-cyclodextrin thioethers, heptakis-6-methylsulfanyl-6
      deoxy-2-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)]-beta-CD (HTMT) and heptakis-6
      thioglyceryl-6-deoxy-beta-CD (HTG) showed gender selectivity in binding of
      hormons: HTMT was selective for testosterone, while HTG was selective for
      estradiol. Solubilization is mainly due to complexation of the A and B rings as
      well as C and D rings of the steroid framework as demonstrated by ROESY NMR
      spectroscopy.

PMID- 28743552
TI  - Near-infrared spectroscopy monitoring and control of the fluidized bed
      granulation and coating processes-A review.
AB  - The fluidized bed granulation and pellets coating technologies are widely used in
      pharmaceutical industry, because the particles made in a fluidized bed have good
      flowability, compressibility, and the coating thickness of pellets are
      homogeneous. With the popularization of process analytical technology (PAT), real
      time analysis for critical quality attributes (CQA) was getting more attention.
      Near-infrared (NIR) spectroscopy, as a PAT tool, could realize the real-time
      monitoring and control during the granulating and coating processes, which could
      optimize the manufacturing processes. This article reviewed the application of
      NIR spectroscopy in CQA (moisture content, particle size and tablet/pellet
      thickness) monitoring during fluidized bed granulation and coating processes.
      Through this review, we would like to provide references for realizing automated
      control and intelligent production in fluidized bed granulation and pellets
      coating of pharmaceutical industry.

PMID- 28743553
TI  - Systematic evaluation of the toxicity and biodistribution of virus mimicking
      mucus-penetrating DLPC-NPs as oral drug delivery system.
AB  - Development of nanoparticle (NP) to simultaneously overcome the diffusion and
      absorption barrier has drawn much attention. Our group recently demonstrated that
      the virus mimicking dilauroylphosphatidylcholine functionalized NP (DLPC-NP)
      could rapidly penetrate across mucus layer and subsequently enter epithelia
      effectively, and exhibited high potential for oral drug delivery. However, the
      safety of the NP has provoked some scientific concerns, which debates from their
      properties that circuiting the protections of mucus and exhibiting strong
      interaction with cell membrane. To be further developed for oral drug delivery,
      the possible toxicity of DLPC-NPs was systematically evaluated in current study.
      For in vitro studies, the exposure of NPs to Caco-2 cells had no effect on cell
      viability and membrane integrity. Then the oxidative stress, cytokine production
      and genotoxicity assay indicated that the NPs did not induce any cell responses.
      The hemolysis test also demonstrated the good hemocompatibility of NPs. For in
      vivo studies, the biodistribution results showed that a large proportion of DLPC
      NPs were detected in liver (0.51 O.D%/g), and followed by kidney (0.39 O.D%/g).
      Then the hematology test, blood biochemical assay and pathological assay were
      performed after a long oral administration periods of 28days. All the results
      indicated that the NPs could not induce any toxic response or histopathological
      lesions. Thus, based on these results, it can be concluded that the zwitterion
      functionalized NPs might be a biocompatible potential candidate for oral drug
      delivery. More importantly, we aimed to emphasis the safety of the nanocarriers
      and also provide a reference for toxicity studies.

PMID- 28743554
TI  - Solubilization of alpha-galactosylceramide in aqueous medium: Impact on Natural
      Killer T cell activation and antitumor responses.
AB  - The potent antitumor effect of alpha-galactosylceramide (alpha-GalCer) is based
      on its recognition by invariant Natural Killer T cells (iNKT) after its capture
      and presentation by antigen presenting cells including dendritic cells (DCs).
      Synthetic alpha-GalCer has already been tested in advanced cancer patients but no
      or only moderate clinical responses were obtained. To optimize alpha-GalCer
      efficacy, we have postulated that alternative formulations impacting its
      molecular organization in aqueous medium could modify DC uptake and iNKT-based
      immune responses. To this end, we have developed two strategies: (1) the
      formulation of alpha-GalCer in non-cationic liposomes and (2) the synthesis of a
      water-soluble alpha-GalCer analogue by anchoring a polyethyleneglycol moiety on
      its sugar head. The biological activities of these new preparations were compared
      to that induced by the classically used Polysorbate 20 alpha-GalCer micelles.
      Both formulations retained their uptake by DCs and activated iNKT cells both in
      vitro and in vivo. Despite a lower cytokine production, the formulations induced
      a potent immune response able to control lung murine carcinoma. In conclusion, it
      is possible to increase alpha-GalCer solubility in aqueous solution without
      limiting its antitumor properties.

PMID- 28743555
TI  - Elevenin regulates the body color through a G protein-coupled receptor NlA42 in
      the brown planthopper Nilaparvata lugens.
AB  - The neuropeptide elevenin and similar neuropeptide precursors are common in some
      invertebrates but their physiological function in most species has not been
      explored. The brown planthopper, Nilaparvata lugens (Stal) has an elevenin-like
      peptide and a G protein-coupled receptor (GPCR) NlA42 that is homologous to the
      elevenin receptor of the annelid Platynereis dumerilii. RNA interference (RNAi)
      mediated knockdown of either Nl-elevenin or the NlA42 gene resulted in cuticle
      melanization. Ion transport peptide (ITP) also induces melanization, but unlike
      ITP, knockdown of NlElevenin and NlA42 did not have any effect on wing expansion
      or activity after eclosion. In wild condition macropterous individuals show a
      darker body color when compared with brachypterous individuals, but RNAi
      experiments suggest that insulin-signaling and Nl-elevenin signaling regulate
      wing morph and body color independently. NlElevenin was predominantly expressed
      in the brain while NlA42 was highly expressed in the abdominal integument and
      brain. A signal Calcium assays using aequorin indicated that NlA42 heterologously
      expressed in HEK293 cells exhibited responses to synthetic Nl-elevenin peptide
      from concentrations as low as 10-9M. These results suggest that neuropeptide Nl
      elevenin is involved in the regulation of melanization through its receptor
      NlA42. This is the first report of a physiological function for elevenin-like
      peptides in insects.

PMID- 28743556
TI  - Increased sensitivity of thyroid hormone-mediated signaling despite prolonged
      fasting.
AB  - Thyroid hormones (TH) can increase cellular metabolism. Food deprivation in
      mammals is typically associated with reduced thyroid gland responsiveness, in an
      effort to suppress cellular metabolism and abate starvation. However, in
      prolonged-fasted, elephant seal pups, cellular TH-mediated proteins are up
      regulated and TH levels are maintained with fasting duration. The function and
      contribution of the thyroid gland to this apparent paradox is unknown and
      physiologically perplexing. Here we show that the thyroid gland remains
      responsive during prolonged food deprivation, and that its function and
      production of TH increase with fasting duration in elephant seals. We discovered
      that our modeled plasma TH data in response to exogenous thyroid stimulating
      hormone predicted cellular signaling, which was corroborated independently by the
      enzyme expression data. The data suggest that the regulation and function of the
      thyroid gland in the northern elephant seal is atypical for a fasted animal, and
      can be better described as, "adaptive fasting". Furthermore, the modeling data
      help substantiate the in vivo responses measured, providing unique insight on
      hormone clearance, production rates, and thyroid gland responsiveness. Because
      these unique endocrine responses occur simultaneously with a nearly strict
      reliance on the oxidation of lipid, these findings provide an intriguing model to
      better understand the TH-mediated reliance on lipid metabolism that is not
      otherwise present in morbidly obese humans. When coupled with cellular, tissue
      specific responses, these data provide a more integrated assessment of thyroidal
      status that can be extrapolated for many fasting/food deprived mammals.

PMID- 28743557
TI  - A high-fat, high-protein diet attenuates the negative impact of casein-induced
      chronic inflammation on testicular steroidogenesis and sperm parameters in adult
      mice.
AB  - The interaction between obesity and chronic inflammation has been studied. Diet
      induced obesity or chronic inflammation could reduce the testicular functions of
      males. However, the mechanism underlying the reproductive effects of fattening
      foods in males with or without chronic inflammation still needs further
      discussion. This study was aimed to investigate the effects of high-fat, high
      protein diet on testicular steroidogenesis and sperm parameters in adult mice
      under physiological and chronic inflammatory conditions. Because casein can
      trigger a non-infectious systemic inflammatory response, we used casein injection
      to induce chronic inflammation in male adult Kunming mice. Twenty-four mice were
      randomly and equally divided into four groups: (i) normal diet+saline (Control);
      (ii) normal diet+casein (ND+CS); (iii) high-fat, high-protein diet+saline
      (HFPD+SI); (iv) high-fat, high-protein diet+casein (HFPD+CS). After 8weeks, there
      was a significant increase in body weight for groups HFPD+SI and HFPD+CS and a
      decrease in group ND+CS compared with the control. The serum levels of tumor
      necrosis factor alpha (TNF-alpha), interleukin-10 (IL-10) and lipid profiles were
      increased markedly in groups ND+CS, HFPD+SI and HFPD+CS compared with the
      control. A remarkable reduction of serum adiponectin level occurred in group
      HFPD+CS compared with group ND+CS. Sperm parameters (sperm count, viability and
      abnormality) were also adversely affected in groups ND+CS and HFPD+SI. Groups
      ND+CS and HFPD+SI showed severe pathological changes in testicular tissues.
      Semiquantitative RT-PCR, Western blot and immunohistochemical staining also
      showed significant reductions in both testicular mRNA and protein levels of
      steroidogenic acute regulatory (StAR) and cytochrome P450scc (CYP11A1) in groups
      HFPD+SI and HFPD+CS compared with the control, whereas testicular mRNA and
      protein levels of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in groups
      HFPD+SI and HFPD+CS significantly increased. The mRNA and protein levels of the
      StAR and 3beta-HSD in group HFPD+CS were both higher than those of in group
      ND+CS. These results indicated that Kunming male mice with high-fat, high-protein
      diet and casein injection for 8weeks can be used to establish a diet-induced
      obesity and chronic systemic inflammation. The sperm parameters in groups ND+CS
      and HFPD+SI decreased accompanied by pathological changes of testicular tissue.
      This resultant effect of reduced serum testosterone levels was associated with
      the overproduction of TNF-alpha and IL-10 and down-regulation of StAR and
      CYP11A1. Under the same casein-induced chronic inflammation condition, the mice
      with high-fat, high-protein diet had better testicular steroidogenesis activity
      and sperm parameters compared with the mice in normal diet, indicating that the
      mice with casein-induced inflammatory injury consuming a high-fat, high-protein
      diet gained weight normally, reduced serum adiponectin level and increased
      testosterone production by an upregulation of 3beta-HSD expression. High-fat,
      high-protein diet attenuated the negative impact of casein-induced chronic
      inflammation on testicular steroidogenesis and sperm parameters.

PMID- 28743558
TI  - The association of nurses' assessment and certainty to pain management and
      outcomes for nursing home residents in Jordan.
AB  - Despite advances in dementia care, pain in people with dementia is still
      undertreated due to poor assessment, poor treatment, and factors relating to
      nurses' critical thinking and decision-making skills. The purpose of the study is
      to examine temporally based relationships between change in behavior, the nurses'
      level of certainty regarding pain, assessment scope, and outcomes of pain. The
      findings of the study were consistent with the Response to Certainty of Pain
      model. This study found high percentage of variances accounted for by nurses'
      level of certainty due to potential unexpected confounding variables. This study
      may provide a new understanding of the relationship between nurses' certainty,
      assessment scope, and patient outcomes for people with dementia. Improved
      understanding of this relationship and how it relates to the problem of
      unrelieved pain in people with dementia is crucial.

PMID- 28743559
TI  - Low-grade endotoxemia, gut permeability and platelet activation in patients with
      impaired fasting glucose.
AB  - BACKGROUND AND AIM: Impaired fasting glucose (IFG) is associated with an
      increased risk of cardiovascular disease but the underlying mechanisms are still
      unclear. Aim of the study was to investigate the interplay between platelet
      activation, lipopolysaccharides (LPS) and markers of oxidative stress in patients
      with IFG and control subjects. METHODS AND RESULTS: We performed a cross
      sectional study including 35 patients with IFG and 35 control subjects who were
      well comparable for age, sex, body mass index and smoking history. Serum levels
      of LPS, zonulin (a marker of gut permeability), oxidized LDL and plasma levels of
      soluble P-selectin, were measured. Patients with IFG had significantly higher
      levels of sP-selectin, LPS, zonulin and oxLDL compared to control subjects. The
      IFG status (beta coefficient: 0.518, p < 0.001), higher LPS (beta coefficient:
      0.352, p = 0.001) and female sex (beta coefficient: 0.179, p = 0.042) were
      independently associated with higher sP-selectin; in addition, oxLDL was
      positively associated with sP-selectin (r = 0.530, p < 0.001) and LPS (r = 0.529,
      p = 0.001). In IFG patients, we found a significant association between LPS and
      zonulin (r = 0.521, p = 0.001); this association was confirmed at multivariable
      analysis (beta coefficient: 0.512, p = 0.007). CONCLUSION: Our study provides
      evidence that patients with IFG have increased platelet activation, and suggests
      LPS as a potential trigger for in vivo platelet activation in this patient
      population.

PMID- 28743560
TI  - Fertility and anogenital distance in women.
AB  - BACKGROUND: Human and animal studies have found an association between prenatal
      androgen exposure and the anogenital distance (AGD). The aims of this study were
      to study the association between female AGD, reproductive health and background
      characteristics. METHODS: This was a cross sectional study, in which AGD were
      measured in 300 pregnant women who were recruited early during the first stage of
      labor. Demographic and health characteristics were collected and studied in
      association with AGD measurements. RESULTS: AGD presented with normal
      distribution (mean 40.3mm+/-10.7) and was positively associated with maternal age
      (beta=0.032, 95%CI 0.007-0.05, p=0.01) and negatively associated with infertility
      treatments (beta=-1.06, 95%CI -1.99 to -0.12, p=0.03). AGD was not associated
      with parity, ethnicity, height and other characteristics. CONCLUSIONS: Adult
      females AGD is associated with age and fertility problems. Adult female AGD, used
      as a marker of early life exposure to EDCs, is possibly associated with
      reproductive characteristics.

PMID- 28743561
TI  - Increased prevalence of colonic adenomas in patients with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) is the most common lethal genetic illness in the
      Caucasian population. Studies have shown that CF patients are at an elevated risk
      of developing colon cancer. Colonic adenomas are the precursors of colon cancer.
      This study aims to determine the prevalence of adenomas in patients with cystic
      fibrosis. METHODS: All patients were recruited prospectively at The Ottawa
      Hospital Cystic Fibrosis Clinic from 2010 through 2015. Baseline demographic and
      cystic fibrosis disease characteristics were collected from the clinic's CF
      patient database. Upon presentation at the endoscopy unit, and after a brief
      history and physical exam, a colonoscopy was performed. Polyps were resected if
      detected and sent to the pathology department for characterization. Findings were
      compared with a control group (pairing each CF patient with 5 age and sex-matched
      controls) of near-average risk patients who underwent a colonoscopy at the same
      center. RESULTS: Of the 33 patients that provided informed consent to participate
      in the study, 30 patients underwent colonoscopy and 13/30 (43.3%) were found to
      have colonic adenomas compared to 7 (4.7%) of the 150 control patients. The
      relative risk ratio for adenoma detection in a CF patient as compared to a
      matched control patient was 9.29 (95% CI 4.04-21.31), p<0.01. CONCLUSIONS:
      Colonic adenomas are more prevalent in CF patients compared to the general
      population. This study suggests the need for additional research to support
      recently published screening guidelines for CF patients.

PMID- 28743562
TI  - Robotic-assisted laparoscopic artificial urinary sphincter and MACE procedure on
      a pediatric patient.
AB  - OBJECTIVE: To describe robotic-assisted laparoscopic artificial urinary sphincter
      (RAL-AUS) placement and a Malone antegrade continent enema (MACE) procedure on a
      6-year-old girl. PATIENTS AND RESULTS: Our patient is a 6-year-old girl with
      myelomeningocele. She was totally incontinent of urine and chronic constipated
      despite aggressive bowel regimen. Preoperative workup included renal and bladder
      ultrasound showing normal findings. Video-urodynamics was also obtained showing
      low leak point pressure (25 cm H2O) with no reflux. RAL-AUS was performed totally
      intra-corporally with no complications. The total operative time was 5 h 42 min.
      Estimated blood loss was minimal. The patient was discharged on postoperative day
      4 with the AUS deactivated. Follow-up cystoscopy and activation of the AUS was
      done 6 weeks later. At 3-month follow-up, the patient was fully recovered and
      remained completely dry between voids. Also her bowel movements improved
      significantly with the MACE. Both patient and family appeared comfortable in
      using the AUS. CONCLUSION: To our knowledge, this is the first case described of
      RAL-AUS placement in the pediatric population. We believe this can be safely
      accomplished with good outcomes. The robotic approach provides an advantage in
      performing deep pelvic surgeries and facilitates concomitant intra-abdominal
      procedures.

PMID- 28743563
TI  - High spatial- and temporal-resolution anthropogenic heat discharge estimation in
      Los Angeles County, California.
AB  - Anthropogenic heat flux (Qf), which originates through energy consumption from
      buildings, industrial plants, vehicle exhausts, and human metabolism releases, is
      an important component in the urban Surface Energy Balance (SEB) system, and is
      key to understanding of many urban environmental issues. The present study
      provided a hybrid Qf modeling approach, which combined the inventory and GIS
      approach to create a 365-day hourly Qf profile at 120 m spatial resolution in Los
      Angeles County, California, USA. Qf was estimated by separate calculation of heat
      release from buildings, traffics, and human metabolism, respectively. The results
      indicated that Qf showed different magnitudes and diurnal patterns between
      workdays (dual-peak shape) and weekends/holidays, and also varied with seasons,
      and land use types. Qf yielded the highest values in the summer workdays, with
      its maximum value of 7.76 w/m2. Qf in hot summer workdays was obviously higher
      than that in the average summer workdays, which caused by higher demands for
      space cooling in buildings, and can reach 8.14 w/m2 at maximum. Building energy
      consumption was identified as the dominant contributor to the Qf in Downtown Los
      Angeles, which was found to have the largest mean Qf throughout the year among
      all neighborhoods. It can be concluded that Qf in the downtown was more
      significant in workdays than that in non-workdays, and its maximum value can
      reach 100 w/m2. It is suggested that our approach may have wider applicability
      for Qf estimation in large areas compared with the existing studies, as all the
      data used were available to the public. A high spatial and temporal Qf profile,
      which can readily be incorporated into urban energy balance and Urban Heat Island
      (UHI) studies, provides valuable data and information for pertinent government
      agencies and researchers.

PMID- 28743564
TI  - Evolving biocatalysis to meet bioeconomy challenges and opportunities.
AB  - The unique selectivity of enzymes, along with their remarkable catalytic
      activity, constitute powerful tools for transforming renewable feedstock and also
      for adding value to an array of building blocks and monomers produced by the
      emerging bio-based chemistry sector. Although some relevant biotransformations
      run at the ton scale demonstrate the success of biocatalysis in industry, there
      is still a huge untapped potential of catalytic activities available for targeted
      valorization of new raw materials, such as waste streams and CO2. For decades,
      the needs of the pharmaceutical and fine chemistry sectors have driven scientific
      research in the field of biocatalysis. Nowadays, such consolidated advances have
      the potential to translate into effective innovation for the benefit of bio-based
      chemistry. However, the new scenario of bioeconomy requires a stringent
      integration between scientific advances and economics, and environmental as well
      as technological constraints. Computational methods and tools for effective big
      data analysis are expected to boost the use of enzymes for the transformation of
      a new array of renewable feedstock and, ultimately, to enlarge the scope of
      biocatalysis.

PMID- 28743565
TI  - Cognitive and emotional impairments after cutaneous intoxication by CEES (a
      sulfur mustard analog) in mice.
AB  - Cognitive and emotional disorders have been reported in veterans intoxicated with
      sulfur mustard (SM) a chemical weapon belonging to the category of vesicating
      agents. However, the intense stress associated with the SM intoxication may
      render difficult determining the exact role played by SM intoxication itself on
      the emergence and maintaining of cognitive disorders. Animal's model would allow
      overcoming this issue. So far, we presently investigated the cognitive and
      emotional impact of an acute cutaneous intoxication with CEES (2-chloroethyl
      ethyl sulfide), a SM analog in C57/Bl6 mice. Our study evidenced that up to 5days
      after a single acute neat CEES skin exposure, compared to controls, mice
      exhibited i) a significant increase in anxiety-like reactivity in an elevated
      plus-maze and in an open-field tasks and ii) an alteration of working memory in a
      sequential alternation task. In contrast, mice submitted to intoxication with a
      diluted CEES solution or hydrochloric acid (HCl) did not show any memory or
      emotional impairments. Given that, Our data shows that a single local cutaneous
      intoxication with neat CEES induced long-lasting cognitive and emotional
      pejorative effects, in accordance with the epidemiological observations in
      veterans. Thus, the single acute neat CEES cutaneous intoxication in mice could
      allow studying the sulfur mustard-induced cognitive and emotional disorders and
      their further counter-measures.

PMID- 28743566
TI  - Mortality prediction in patients with acute kidney injury requiring renal
      replacement therapy after cardiac surgery.
AB  - BACKGROUND AND OBJECTIVE: Acute kidney injury (AKI) is a common and potentially
      serious postoperative complication after cardiac surgery, and it remains a cause
      of major morbidity and mortality. The aim of our study was to assess the
      prognostic illness severity score and to estimate the significant risk factors
      for poor outcome of patients with AKI requiring renal replacement therapy (RRT)
      after cardiac surgery. MATERIALS AND METHODS: We retrospectively analyzed data of
      adult (>18 years) patients (n=111) who underwent open heart surgery and had
      developed AKI with need for RRT. Prognostic illness severity scores were
      calculated and perioperative risk factors of lethal outcome were assessed at the
      RRT initiation time. We defined three illness severity scores: Acute Physiology
      and Chronic Health Evaluation (APACHE II) as a general score, Sequential Organ
      Failure Assessment (SOFA) as an organ failure score, and Liano score as a kidney
      specific disease severity score. Logistic regression was also used for the
      multivariate analysis of mortality risk factors. RESULTS: Hospital mortality was
      76.5%. More than 7% of patients remained dialysis-dependent after their discharge
      from the hospital. The prognostic abilities of the scores were assessed for their
      discriminatory power. The area under the receiver-operating characteristic (ROC)
      curve of SOFA score was 0.719 (95% CI, 0.598-0.841), of Liano was 0.661 (95% CI,
      0.535-0.787) and 0.668 (95% CI, 0.550-0.785) of APACHE II scores. From 16
      variables analyzed for model selection, we reached a final logistic regression
      model, which demonstrated four variables significantly associated with patients'
      mortality. Glasgow coma score<14 points (OR=3.304; 95% CI, 1.130-9.662; P=0.003),
      mean arterial blood pressure (MAP)<63.5mmHg (OR=3.872; 95% CI, 1.011-13.616;
      P=0.035), serum creatinine>108.5MUmol/L (OR=0.347; 95% CI, 0.123-0.998; P=0.046)
      and platelet count<115*109/L (OR=3.731; 95% CI, 1.259-11.054; P=0.018) were
      independent risk factors for poor patient outcome. CONCLUSIONS: Our study
      demonstrated that SOFA score estimation is the most accurate to predict the fatal
      outcome in patients with AKI requiring RRT after cardiac surgery. Lethal patient
      outcome is related to Glasgow coma score, mean arterial blood pressure,
      preoperative serum creatinine and postoperative platelet count.

PMID- 28743567
TI  - Androgenic-anabolic steroids inhibited post-exercise hypotension: a case control
      study.
AB  - BACKGROUND: There is evidence of hypertensive effects caused by anabolic
      androgenic steroids (AAS). A single exercise session promotes the acute reduction
      of blood pressure, but the effects of AAS on this phenomenon are unknown.
      OBJECTIVES: To investigate the post-exercise blood pressure response in
      androgenic-anabolic steroid users. METHODS: Thirteen AAS users (23.9+/-4.3 years
      old) and sixteen controls (22.1+/-4.5 years old) performed a session of aerobic
      exercise. Heart rate and blood pressure were assessed before exercise and during
      a 60min post-exercise resting period. Repeated ANOVA measures were used to
      determine differences between the groups. RESULTS: While the control group had a
      significant reduction in post-exercise systolic blood pressure of up to 13.9+/
      11.6mmHg at 40min, this phenomenon was limited among AAS users who reached a
      maximum of 6.2+/-11.5mmHg at 60min. The between groups comparison revealed
      significant higher post-exercise hypotension (PEH) for the control group at 30min
      (-12.9+/-14.1mmHg versus -2.9+/-7.6mmHg), 40min (-13.9+/-11.6mmHg versus -2.5+/
      8.3mmHg), 50min (-13.9+/-13.9mmHg versus -5.0+/-7.9mmHg) and 60min (-12.5+/
      12.8mmHg versus -6.2+/-11.5mmHg). There was no significant diastolic PEH in any
      of the groups. CONCLUSIONS: This study demonstrated impaired systolic post
      exercise hypotension as a new adverse effect of AAS usage.

PMID- 28743568
TI  - Phospholipase A2 Inhibitor from Crotalus durissus terrificus rattlesnake: Effects
      on human peripheral blood mononuclear cells and human neutrophils cells.
AB  - Crotalus Neutralizing Factor (CNF) is an inhibitor of phospholipase A2 (PLA2),
      present in the blood plasma of Crotalus durissus terrificus snake. This inhibitor
      neutralizes the lethal and enzymatic activity of crotoxin, the main neurotoxin
      from this venom. In this study, we investigated the effects of CNF on the
      functionality of human peripheral blood mononuclear cells (PBMCs) and human
      neutrophils. The following parameters were evaluated: viability and
      proliferation, chemotaxis, cytokines and LTB4 production, cytosolic PLA2s
      activity, myeloperoxidase (MPO) and superoxide anion (O2-) production. CNF showed
      no toxicity on PBMCs or neutrophils, and acts by stimulating the release of TNF
      alpha and LTB4, but neither stimulates IL-10 and IL-2 nor affects PBMCs
      proliferation and O2- release. In neutrophils, CNF induces chemotaxis but does
      not induce the release of both MPO and O2-. However, it induces LTB4 and IL-8
      production. These data show the influence of CNF on PBMCs' function by inducing
      TNF-alpha and LTB4 production, and on neutrophils, by stimulating chemotaxis and
      LTB4 production, via cytosolic PLA2 activity, and IL-8 release. The inflammatory
      profile produced by CNF is shown for the first time. Our present results suggest
      that CNF has a role in activation of leukocytes and exert proinflammatory effects
      on these cell.

PMID- 28743569
TI  - Structural characterization, catalytic, kinetic and thermodynamic properties of
      Keratinase from Bacillus pumilus FH9.
AB  - Bacillus pumilus FH9 keratinase was purified to homogeneity with a 59.9% yield
      through a series of three steps. The purified enzyme was a monomeric protein with
      a molecular mass around 50kDa and containing 7.3% carbohydrates. The pure B.
      pumilus FH9 keratinase was optimally active at pH 9.0 and 60 degrees C. The
      calculated activation energy for keratin hydrolysis was 24.52kJmol-1 and its
      temperature quotient (Q10) was 1.19. The calculated values of thermodynamic
      parameters for keratin hydrolysis were as follows: DeltaH*=21.75kJmol-1,
      DeltaG*=65.86kJmol-1 DeltaS*=-132.46Jmol-1K-1, (DeltaG*E-S)=4.74kJmol-1 and
      DeltaG*E-T=-11.254kJmol-1. The pure keratinase exhibited Km, Vmax, kcat and
      kcat/Km of 5.55mg/ml keratin, 5882Umgprotein-1 323.54s-1 and 58.28 (s-1/mgml-1).
      The calculated half-life time at 50, 60, 70 and 80 degrees C was 90.69, 59.1,
      16.62 and 9.48min, respectively. Similarly, the thermodynamic parameters for
      irreversible thermal inactivation at temperature ranging from 50 to 80 degrees C
      were determined. The pure enzyme was stimulated by Ca2+ and Mg2+. However, Zn2+,
      EDTA, Co2+ and Hg2+ significantly inhibited the enzyme activity. The purified
      enzyme was able to hydrolyze different substrates showing its higher proteolytic
      activity on casein, bovine serum albumin, and collagen, followed by feather, horn
      and wool.

PMID- 28743570
TI  - Chemical structure and anti-inflammatory effect of polysaccharides obtained from
      infusion of Sedum dendroideum leaves.
AB  - Sedum dendroideum is popularly known as balsam and used for treatment of
      inflammatory disorders. Two polysaccharides (RSBAL-H2O and RSBAL-0.5) were
      isolated from infusion of its dried leaves, using dialysis at 100kDa cut-off
      membrane and anion exchange chromatography. Methylation and NMR analyses showed
      that RSBAL-H2O is a highly methyl-esterified homogalacturonan, constituted by (1
      >4)-alpha-D-GalA residues, whereas RSBAL-0.5 is a highly methyl-esterified
      homogalacturonan branched at O-3, probably by type II arabinogalactans and
      arabinans. In this study we showed that these balsam polysaccharides stimulate
      secretion of the cytokines TNF-alpha, IL-1beta and IL-10 by THP-1 macrophages,
      acting as immunostimulatory agents. But, on the other hand, they reduce TNF-alpha
      and IL1-beta secretion induced by a pro-inflammatory agent (LPS), showing anti
      inflammatory effect.

PMID- 28743571
TI  - Optimization of water-soluble polysaccharides from stem lettuce by response
      surface methodology and study on its characterization and bioactivities.
AB  - Stem lettuce is widely consumed as a vegetable in China. It is also used as a
      traditional Chinese medicine for a long time. Up to now, no information is
      available for stem lettuce polysaccharide (SLP). In this study, extraction
      optimization, characterization, and antioxidant activity of SLP was
      investigated.The maximum SLP yield of 20.89% was obtained under the optimal
      extraction conditions as follows: extraction temperature 95 degrees C, extraction
      time 3.3h and ratio of water to material 25mL/g. The sulfate content of SLP was
      5.82% and the main monosaccharides were GalA, Gal, and Ara with a mole ratio of
      49.2: 23.3: 22.9. FT-IR spectrum and HPGPC result further indicated that SLP is a
      sulfated polydisperse heterpolysaccharide. Congo-red test and AFM scan indicated
      that SLP might be branching and intertwining structure with triple helix
      conformation. Moreover, SLP exhibited potent antioxidant activity and alpha
      amylase inhibitory activity, hence it could be used as a potential natural
      antioxidant and hypoglycemic agent in medicine or functional food fields.

PMID- 28743572
TI  - Influence of aggregation on characterization of dilute xanthan solutions.
AB  - Xanthan is an extracellular polysaccharide of polyanionic nature widely used in
      industrial processes as flow modifier. Its characterization in dilute solutions
      is complicated by the strong tendency to aggregation. We explore the possibility
      to obtain dilute xanthan solutions without aggregates. We applied some steps of
      the sample preparation procedures from previous works on xanthan, such as
      ultrasonication, heating and micro filtration. The influence of this type of
      treatment on the observed properties of xanthan 0.1M NaCl aqueous solutions is
      studied. Renaturalization of xanthan solutions above the overlap concentration
      does not break the aggregates but, on the opposite, produces the ones that are
      more resistant to ultrasound. Ultrasonication breaks only large aggregates and at
      long sonication times brings the risk of the single chain degradation. The best
      results are provided by a procedure that combines a short ultrasonication time
      followed by micro filtration but it is impossible to obtain a solution completely
      free of small aggregates by conventional sample preparation methods.
      Nevertheless, a significant reduction of large aggregates results in a linear
      concentration dependence of xanthan reduced viscosity, which allows more
      confident determination of the intrinsic viscosity. Another advantage of large
      aggregates removal is a possibility of physical interpretation of xanthan
      molecular parameters by static light scattering, taking into account its
      association tendency.

PMID- 28743573
TI  - Loading of chitosan - Nano metal oxide hybrids onto cotton/polyester fabrics to
      impart permanent and effective multifunctions.
AB  - New and durable multifunctional properties of cotton/polyester blended fabrics
      were developed through loading of chitosan (Cs) and various metal oxide
      nanoparticles (MONPs) namely ZnO, TiO2, and SiO2 onto fabric surface using citric
      acid/Sodium hypophosphite for ester-crosslinking and creating new anchoring and
      binding sites, COOH groups, onto the ester-crosslinked fabrics surface. The
      surface morphology and the presence of active ingredients (Cs & MONPs) onto
      selected - coated fabric samples were analyzed by SEM images and confirmed by EDS
      spectrums. The influence of various finishing formulations on some performance
      and functional properties such as wettability, antibacterial activity, UV
      protection, self-cleaning, resiliency and durability to wash were studied. The
      obtained results revealed that the extent of improvement in the imparted
      functional properties is governed by type of loaded-hybrid and follows the
      decreasing order: Cs-TiO2NPs>Cs-ZnONPs>SiO2NPs>Cs alone, as well as kind of
      substrate cotton/polyester (65/35)>cotton/polyester (50/50). Moreover, after 15
      washing cycles, the durability of the imparted functional properties of
      Cs/TiO2NPs - loaded substrates marginally decreased indicating the strong
      fixation of the hybrid components onto the ester-crosslinked substrates. The
      obtained bioactive multifunctional textiles can be used for producing eco
      friendly protective textile materials for numerous applications.

PMID- 28743574
TI  - Effect of germination on the structures and physicochemical properties of
      starches from brown rice, oat, sorghum, and millet.
AB  - Four selected grains (brown rice, oat, sorghum, and millet) were subjected to
      germinate and changes in granule morphology, molecular structure, crystalline
      structure, and physicochemical properties of isolated starch were investigated.
      The germinated starches showed pits and holes on the surface of the starch
      granules and the particle size distributions shifted slightly to smaller size as
      the germination time increased. Germination led to decrease in amylose content,
      while molecular weights of the germinated starches showed no significant changes.
      The relative crystallinity of all selected grain starches decreased significantly
      during germination. Compared to the native starches, the germinated starches had
      lower retrogradation enthalpy. Brown rice and oat starches exhibited marginal
      increases in peak viscosities, whereas those of sorghum and millet starches
      decreased significantly during germination. Amylose leaching of brown rice and
      oat starches decreased after germination, whereas sorghum and millet starches
      showed an increase in amylose leaching.

PMID- 28743575
TI  - Efficacy of vinyl imidazole grafted cationized pullulan and dextran as gene
      delivery vectors: A comparative study.
AB  - The present study deals with efficacy evaluation of two cationised
      polysaccharides - Pullulan PEI and Dextran PEI as gene delivery vector after
      grafting with vinyl imidazole. Chemical modifications of these polysaccharides
      were confirmed by FTIR and NMR. Nanoplex formed from dextran PEI imidazole (DPI)
      were of smaller size and possess greater positive charge as compared to that of
      pullulan PEI imidazole (PPI). MTT assay carried out in C6 and HeLa cell lines
      revealed that both PPI and DPI are cytocompatible and the percentage cell
      viability is higher for former. Though DPI and PPI derivatives showed similar
      cellular uptake, the cell morphology was maintained with later and this may due
      to the high molecular flexibility of pullulan that masks the cytotoxicity of PEI.
      Similarly transfection studies carried out with p53 plasmid also revealed that
      PPI derivatives promote more apoptosis in both C6 and HeLa cell lines as compared
      to that of DPI derivatives. Based on cytocompatibility and transfection
      efficiency, PPI was found to be a better gene delivery vector that can be further
      explored for in vivo applications.

PMID- 28743576
TI  - A review on protein misfolding, aggregation and strategies to prevent related
      ailments.
AB  - This review aims to highlight the fundamental mechanism of protein misfolding
      leading to protein aggregation and associated diseases. It also aims to
      anticipate novel therapeutic strategies with which to prevent or treat these
      highly debilitating conditions linked to these pathologies. The failure of a
      protein to correctly fold de novo or to remain correctly folded can have profound
      consequences on a living system especially when the cellular quality control
      processes fail to eliminate the rogue proteins. The core cause of over 20
      different human diseases which have now been designated as 'conformational
      diseases' including neurodegenerative diseases such as Alzheimer's disease (AD),
      Huntington's disease (HD) and Parkinson's disease (PD) etc. A comprehensive study
      on protein misfolding, aggregation, and the outcomes of the effects of cytotoxic
      aggregates will lead to understand the aggregation-mediated cell toxicity and
      serves as a foundation for future research in development of promising therapies
      and drugs. This review has also shed light on the mechanism of protein misfolding
      which leads to its aggregation and hence the neurodegeneration. From these
      considerations, one could also envisage the possibility that protein aggregation
      may be exploited by nature to perform specific physiological functions in
      differing biological contexts.

PMID- 28743577
TI  - An environmentally friendly ball milling process for recovery of valuable metals
      from e-waste scraps.
AB  - The present study reports a mechanochemical (MC) process for effective recovery
      of copper (Cu) and precious metals (i.e. Pd and Ag) from e-waste scraps. Results
      indicated that the mixture of K2S2O8 and NaCl (abbreviated as K2S2O8/NaCl
      hereafter) was the most effective co-milling reagents in terms of high recovery
      rate. After co-milling with K2S2O8/NaCl, soluble metallic compounds were produced
      and consequently benefit the subsequent leaching process. 99.9% of Cu and 95.5%
      of Pd in the e-waste particles could be recovered in 0.5mol/L diluted HCl in
      15min. Ag was concentrated in the leaching residue as AgCl and then recovered in
      1mol/L NH3 solution. XRD and XPS analysis indicated that elemental metals in the
      raw materials were transformed into their corresponding oxidation state during
      ball milling process at low temperature, implying that solid-solid phase
      reactions is the reaction mechanism. Based on the results and thermodynamic
      parameters of the probable reactions, possible reaction pathways during ball
      milling were proposed. Suggestion on category of e-waste for ball milling process
      was put forward according to the experiment results. The designed metal recovery
      process of this study has the advantages of highly recovery rate and quick
      leaching speed. Thus, this study offers a promising and environmentally friendly
      method for recovering valuable metals from e-waste.

PMID- 28743578
TI  - Effects of an applied voltage on direct interspecies electron transfer via
      conductive materials for methane production.
AB  - Direct interspecies electron transfer (DIET) between exoelectrogenic bacteria and
      methanogenic archaea via conductive materials is reported as an efficient method
      to produce methane in anaerobic organic waste digestion. A voltage can be applied
      to the conductive materials to accelerate the DIET between two groups of
      microorganisms to produce methane. To evaluate this hypothesis, two sets of
      anaerobic serum bottles with and without applied voltage were used with a pair of
      graphite rods as conductive materials to facilitate DIET. Initially, the methane
      production rate was similar between the two sets of serum bottles, and later the
      serum bottles with an applied voltage of 0.39V showed a 168% higher methane
      production rate than serum bottles without an applied voltage. In cyclic
      voltammograms, the characteristic redox peaks for hydrogen and acetate oxidation
      were identified in the serum bottles with an applied voltage. In the microbial
      community analyses, hydrogenotrophic methanogens (e.g. Methanobacterium) were
      observed to be abundant in serum bottles with an applied voltage, while
      methanogens utilizing carbon dioxide (e.g., Methanosaeta and Methanosarcina) were
      dominant in serum bottles without an applied voltage. Taken together, the applied
      voltage on conductive materials might not be effective to promote DIET in methane
      production. Instead, it appeared to generate a condition for hydrogenotrophic
      methanogenesis.

PMID- 28743579
TI  - Seeking to enhance the bioenergy of municipal sludge: Effect of alkali pre
      treatment and soluble organic matter supplementation.
AB  - The aim of this research is to enhance the mesophilic anaerobic digestion of
      municipal sludge from Cadiz-San Fernando (Spain) wastewater treatment plant at
      20days hydraulic retention time (HRT). Two different strategies were tested to
      improve the process: co-digestion with the addition of soluble organic matter (1%
      v/v); and alkali sludge pre-treatment (NaOH) prior to co-digestion with glycerine
      (1% v/v). Methane production (MP) was substantially enhanced (from 0.36+/-0.09 L
      CH4 l/d to 0.85+/-0.16 L CH4 l/d), as was specific methane production (SMP) (from
      0.20+/-0.05 L CH4/g VS to 0.49+/-0.09 L CH4/g VS) when glycerine was added. The
      addition of glycerine does not seem to affect sludge stability, the quality of
      the effluent in terms of pH and organic matter content, i.e. volatile fatty acids
      (VFA), soluble organic matter and total volatile solid, or process stability
      (VFA/Alkalinity ratio<0.4). Alkali pre-treatment prior to co-digestion resulted
      in a high increase in soluble organic loading rates (more than 20%) and
      acidification yield (more than 50%). At 20days HRT, however, it led to overload
      of the system and total destabilization of the mesophilic anaerobic co-digestion
      of sewage sludge and glycerine.

PMID- 28743580
TI  - Comparison of balance strategies in mountain climbers during real altitude
      exposure between 1.500m and 3.200m: Effects of age and expertise.
AB  - PURPOSE: The aim of this study was to estimate the effect of altitude (1500m vs.
      3200m) on balance strategies, and to determine the influence of age (> or <40
      years) and expertise (> or <20days of mountain climbing/year) on postural
      stability at altitude. METHOD: Eighty-nine volunteer mountaineers were tested at
      1500m, 3200m immediately after exiting the cable car and at 3200m following the
      climb and return. Double-leg stance with eyes closed and single-leg stance with
      eyes open were tested. The center of pressure (CoP) was recorded for 12.8s using
      a stabilometric force platform. Length, surface, ratio (length/surface), and
      average speed of the CoP, as well as lower limb loading were calculated. Groups
      and altitudes were compared using ANOVA. Significance was set to p<0.05. RESULTS:
      CoP ratio was significantly higher during both balance conditions at 3200m
      compared to 1500m (p<0.05). Lower limb loading was symmetrical at 1500m but not
      at 3200m (p<0.05). There was no influence of age or expertise at 1500m (p=NS),
      however at 3200m, older subjects and subjects with less expertise had greater
      length and surface of the CoP, showing more instability (p<0.05). CONCLUSION:
      Postural stability was immediately reduced on arrival at 3200m, particularly in
      subjects above the age of 40 years with less expertise.

PMID- 28743581
TI  - Caspase-1 inhibitor regulates humoral responses in experimental autoimmune
      myasthenia gravis via IL-6- dependent inhibiton of STAT3.
AB  - We have previously demonstrated that Cysteinyl aspartate-specific proteinase-1
      (caspase-1) inhibitor ameliorates experimental autoimmune myasthenia gravis
      (EAMG) by inhibited cellular immune response, via suppressing DC IL-1 beta, CD4+
      T and gammadT cells IL-17 pathways. In this study, we investigated the effect of
      caspase-1 inhibitor on humoral immune response of EAMG and further explore the
      underlying mechanisms. An animal model of MG was induced by region 97-116 of the
      rat AChR alpha subunit (R97-116 peptide) in Lewis rats. Rats were treated with
      caspase-1 inhibitor Ac-YVAD-cmk intraperitoneally (i.p.) every second day from
      day 13 after the first immunization. Flow cytometry, western blot,
      immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were performed
      to evaluate the neuroprotective effect of caspase-1 inhibitor on humoral immune
      response of EAMG. The results showed that caspase-1 inhibitor reduced the
      relative affinity of anti-R97-116 IgG, suppressed germinal center response,
      decreased follicular helper T cells, and increased follicular regulatory T cells
      and regulatory B cells. In addition, we found that caspase-1 inhibitor inhibited
      humoral immunity response in EAMG rats via suppressing IL-6-STAT3-Bcl-6 pathways.
      These results suggest that caspase-1 inhibitor ameliorates EAMG by regulating
      humoral immune response, thus providing new insights into the development of
      myasthenia gravis and other autoimmune diseases therapies.

PMID- 28743582
TI  - Acute ethanol and taurine intake affect absolute alpha power in frontal cortex
      before and after exercise.
AB  - Taurine and alcohol has been popularly ingested through energy drinks. Reports
      from both compounds shows they are active on nervous system but little is known
      about the acute effect of these substances on the frontal cortex in an exercise
      approach. The aim of this study was to determine the effects of 0,6mldL-1 of
      ethanol (ET), 6g of taurine (TA), and taurine with ethanol (TA+ET) intake on
      absolute alpha power (AAP) in the frontal region, before and after exercise. Nine
      participants were recruited, five women (22+/-3years) and four men (26+/-5years),
      for a counterbalanced experimental design. For each treatment, the tests were
      performed considering three moments: "baseline", "peak" and "post-exercise". In
      the placebo treatment (PL), the frontal areas showed AAP decrease at the post
      exercise. However, in the TA, AAP decreased at peak and increased at post
      exercise. In the ET treatment, AAP increased at the peak moment for the left
      frontal electrodes. In the TA+ET treatment, an AAP increase was observed at peak,
      and it continued after exercise ended. These substances were able to produce
      electrocortical activity changes in the frontal regions after a short duration
      and low intensity exercise. Left and right regions showed different AAP dynamics
      during peak and post-exercise moments when treatments were compared.

PMID- 28743583
TI  - Development of a TaqMan-based real-time PCR assay for the specific detection of
      porcine circovirus 3.
AB  - Porcine circovirus 3 (PCV3) is a novel circovirus that was associated with
      porcine dermatitis and nephropathy syndrome, reproductive failure, and
      multisystemic inflammation. The objective of this study was to develop a rapid,
      simple, specific and sensitive TaqMan-based real-time PCR assay for PCV3
      detection. Specific primers and probe were designed for the cap gene of PCV3
      within the conserved region of viral genome. The assay was highly specific for
      PCV3, without cross-reactions with other non-targeted pig viruses. The detection
      limit of this assay was 102 copies. The assay had an efficiency of 95.7%, a
      regression squared value (R2) of 0.994 and showed a linear range of 102-107
      copies PCV3 DNA per reaction. The assay was also very reproducible, with the
      intra- and inter-assay coefficient of variation less than 2.0%. For the 112
      archived clinical samples collected from 2014 to March 2017, the PCV3 positive
      ratio was 12.5% (14/112) with the real-time PCR. The presence of the PCV3 dated
      back to at least 2014 in China and samples collected in 2017 had the highest PCV3
      positive ratio (46.7%, 7/15). The real-time PCR assay could be used for detection
      of PCV3 in epidemiological and pathogenesis studies.

PMID- 28743584
TI  - A single-plasmid reverse genetics system for the rescue of non-segmented negative
      strand RNA viruses from cloned full-length cDNA.
AB  - Reverse genetics systems for non-segmented negative-strand RNA viruses rely on co
      transfection of a plasmid containing the full-length viral cDNA and helper
      plasmids encoding essential viral replication proteins. Here, a system is
      presented in which virus can be rescued from a single plasmid without the need
      for helper plasmids in cells infected with a host-restricted recombinant poxvirus
      that expresses T7 RNA polymerase. This approach relies on the insertion of T7
      promoter sequences in the viral cDNA at positions that allow transcription of sub
      genomic RNAs encoding essential viral replication proteins.

PMID- 28743585
TI  - The resolution of ambiguity as the basis for life: A cellular bridge between
      Western reductionism and Eastern holism.
AB  - Boundary conditions enable cellular life through negentropy, chemiosmosis, and
      homeostasis as identifiable First Principles of Physiology. Self-referential
      awareness of status arises from this organized state to sustain homeostatic
      imperatives. Preferred homeostatic status is dependent upon the appraisal of
      information and its communication. However, among living entities, sources of
      information and their dissemination are always imprecise. Consequently, living
      systems exist within an innate state of ambiguity. It is presented that cellular
      life and evolutionary development are a self-organizing cellular response to
      uncertainty in iterative conformity with its basal initiating parameters. Viewing
      the life circumstance in this manner permits a reasoned unification between
      Western rational reductionism and Eastern holism.

PMID- 28743586
TI  - Intrinsic regulation of sinoatrial node function and the zebrafish as a model of
      stretch effects on pacemaking.
AB  - Excitation of the heart occurs in a specialised region known as the sinoatrial
      node (SAN). Tight regulation of SAN function is essential for the maintenance of
      normal heart rhythm and the response to (patho-)physiological changes. The SAN is
      regulated by extrinsic (central nervous system) and intrinsic (neurons, peptides,
      mechanics) factors. The positive chronotropic response to stretch in particular
      is essential for beat-by-beat adaptation to changes in hemodynamic load. Yet, the
      mechanism of this stretch response is unknown, due in part to the lack of an
      appropriate experimental model for targeted investigations. We have been
      investigating the zebrafish as a model for the study of intrinsic regulation of
      SAN function. In this paper, we first briefly review current knowledge of the
      principal components of extrinsic and intrinsic SAN regulation, derived primarily
      from experiments in mammals, followed by a description of the zebrafish as a
      novel experimental model for studies of intrinsic SAN regulation. This mini
      review is followed by an original investigation of the response of the zebrafish
      isolated SAN to controlled stretch. Stretch causes an immediate and continuous
      increase in beating rate in the zebrafish isolated SAN. This increase reaches a
      maximum part way through a period of sustained stretch, with the total change
      dependent on the magnitude and direction of stretch. This is comparable to what
      occurs in isolated SAN from most mammals (including human), suggesting that the
      zebrafish is a novel experimental model for the study of mechanisms involved in
      the intrinsic regulation of SAN function by mechanical effects.

PMID- 28743587
TI  - Aesthetic outcomes of liposuction after breast reconstruction using exclusive fat
      grafting.

PMID- 28743588
TI  - Determining the outcomes of post-mastectomy radiation therapy delivered to the
      definitive implant in patients undergoing one- and two-stage implant-based breast
      reconstruction: A systematic review and meta-analysis.
AB  - BACKGROUND: Post-mastectomy radiation therapy (PMRT) is known to increase the
      complication rate and implant loss in implant-based breast reconstruction. The
      purpose of this study was to systematically review the literature regarding the
      outcome of PMRT delivered to the permanent/definitive implant. METHODS:
      Systematic review and meta-analysis of studies involving immediate implant-based
      reconstruction and PMRT when delivered to the permanent implant. RESULTS: Seven
      studies included 2921 patients (520 PMRT, 2401 control). PMRT was associated with
      significant increase in capsular contracture (7 studies, 2529 patients, 494 PMRT,
      2035 control, OR 10.21, 95% CI 3.74 to 27.89, p < 0.00001). In addition, PMRT was
      associated with a significant increase in revisional surgery (7 studies, 2921
      patients, 520 PMRT, 2401 control, OR 2.18, 95% CI 1.33 to 3.57, p = 0.002) and
      reconstructive failure (6 studies, 2814 patients, 496 PMRT, 2318 control, OR
      2.52, 95% CI 1.48 to 4.29, p+0.0007). Moreover, it was associated with a
      significant reduction in patient satisfaction (4 studies, 468 patients, 138 PMRT,
      294 control, OR 0.29, 95% CI 0.15 to 0.57, p = 0.0003) and cosmetic outcome (4
      studies, 1317 patients, 238 PMRT, 1009 control, OR 28, 95% CI. 0.11 to 0.67, p =
      0.005). CONCLUSIONS: This meta-analysis demonstrates that within the first 5
      years, post implant-based reconstruction for those patients who receive PMRT, the
      rates of adverse events are increased, and there is a significant reduction in
      patient satisfaction and cosmetic outcome.

PMID- 28743589
TI  - Density functionalized [RuII(NO)(Salen)(Cl)] complex: Computational photodynamics
      and in vitro anticancer facets.
AB  - Photodynamic therapy (PDT) is a treatment that uses photosensitizing agents to
      kill cancer cells. Scientific community has been eager for decades to design an
      efficient PDT drug. Under such purview, the current report deals with the
      computational photodynamic behavior of ruthenium(II) nitrosyl complex containing
      N, N'-salicyldehyde-ethylenediimine (SalenH2), the synthesis and X-ray
      crystallography of which is already known [Ref. 38,39]. Gaussian 09W software
      package was employed to carry out the density functional (DFT) studies. DFT
      calculations with Becke-3-Lee-Yang-Parr (B3LYP)/Los Alamos National Laboratory 2
      Double Z (LanL2DZ) specified for Ru atom and B3LYP/6-31G(d,p) combination for all
      other atoms were used using effective core potential method. Both, the ground and
      excited states of the complex were evolved. Some known photosensitizers were
      compared with the target complex. Pthalocyanine and porphyrin derivatives were
      the compounds selected for the respective comparative study. It is suggested that
      effective photoactivity was found due to the presence of ruthenium core in the
      model complex. In addition to the evaluation of theoretical aspects in vitro
      anticancer aspects against COLO-205 human cancer cells have also been carried out
      with regard to the complex. More emphasis was laid to extrapolate DFT to depict
      the chemical power of the target compound to release nitric oxide. A promising
      visible light triggered nitric oxide releasing power of the compound has been
      inferred. In vitro antiproliferative studies of [RuCl3(PPh3)3] and
      [Ru(NO)(Salen)(Cl)] have revealed the model complex as an excellent anticancer
      agent. From IC50 values of 40.031mg/mL in former and of 9.74mg/mL in latter, it
      is established that latter bears more anticancer potentiality. From overall study
      the DFT based structural elucidation and the efficiency of NO, Ru and Salen co
      ligands has shown promising drug delivery property and a good candidacy for both
      chemotherapy as well as light therapy.

PMID- 28743590
TI  - Sequence Specificity in the Entropy-Driven Binding of a Small Molecule and a
      Disordered Peptide.
AB  - Approximately one-third of the human proteome is made up of proteins that are
      entirely disordered or that contain extended disordered regions. Although these
      disordered proteins are closely linked with many major diseases, their binding
      mechanisms with small molecules remain poorly understood, and a major concern is
      whether their specificity can be sufficient for drug development. Here, by
      studying the interaction of a small molecule and a disordered peptide from the
      oncogene protein c-Myc, we describe a "specific-diffuse" binding mechanism that
      exhibits sequence specificity despite being of entropic nature. By combining NMR
      spectroscopy, biophysical measurements, statistical inference, and molecular
      simulations, we provide a quantitative measure of such sequence specificity and
      compare it to the case of the interaction of urea, which is diffuse but not
      specific. To investigate whether this type of binding can generally modify
      intermolecular interactions, we show that it leads to an inhibition of the
      aggregation of the peptide. These results suggest that the binding mechanism that
      we report may create novel opportunities to discover drugs that target disordered
      proteins in their monomeric states in a specific manner.

PMID- 28743591
TI  - Terminology supported archiving and publication of environmental science data in
      PANGAEA.
AB  - Exemplified on the information system PANGAEA, we describe the application of
      terminologies for archiving and publishing environmental science data. A
      terminology catalogue (TC) was embedded into the system, with interfaces allowing
      to replicate and to manually work on terminologies. For data ingest and
      archiving, we show how the TC can improve structuring and harmonizing lineage and
      content descriptions of data sets. Key is the conceptualization of measurement
      and observation types (parameters) and methods, for which we have implemented a
      basic syntax and rule set. For data access and dissemination, we have improved
      findability of data through enrichment of metadata with TC terms. Semantic
      annotations, e.g. adding term concepts (including synonyms and hierarchies) or
      mapped terms of different terminologies, facilitate comprehensive data
      retrievals. The PANGAEA thesaurus of classifying terms, which is part of the TC
      is used as an umbrella vocabulary that links the various domains and allows drill
      downs and side drills with various facets. Furthermore, we describe how TC terms
      can be linked to nominal data values. This improves data harmonization and
      facilitates structural transformation of heterogeneous data sets to a common
      schema. Technical developments are complemented by work on the metadata content.
      Over the last 20 years, more than 100 new parameters have been defined on average
      per week. Recently, PANGAEA has increasingly been submitting new terms to various
      terminology services. Matching terms from terminology services with our parameter
      or method strings is supported programmatically. However, the process ultimately
      needs manual input by domain experts. The quality of terminology services is an
      additional limiting factor, and varies with respect to content, editorial,
      interoperability, and sustainability. Good quality terminology services are the
      building blocks for the conceptualization of parameters and methods. In our view,
      they are essential for data interoperability and arguably the most difficult
      hurdle for data integration. In summary, the application of terminologies has a
      mutual positive effect for terminology services and information systems such as
      PANGAEA. On both sides, the application of terminologies improves content,
      reliability and interoperability.

PMID- 28743592
TI  - Piloting water quality testing coupled with a national socioeconomic survey in
      Yogyakarta province, Indonesia, towards tracking of Sustainable Development Goal
      6.
AB  - There remains a pressing need for systematic water quality monitoring strategies
      to assess drinking water safety and to track progress towards the Sustainable
      Development Goals (SDG). This study incorporated water quality testing into an
      existing national socioeconomic survey in Yogyakarta province, Indonesia; the
      first such study in Indonesia in terms of SDG tracking. Multivariate regression
      analysis assessed the association between faecal and nitrate contamination and
      drinking water sources household drinking water adjusted for wealth, education
      level, type of water sources and type of sanitation facilities. The survey
      observed widespread faecal contamination in both sources for drinking water
      (89.2%, 95%CI: 86.9-91.5%; n=720) and household drinking water (67.1%, 95%CI:
      64.1-70.1%; n=917) as measured by Escherichia coli. This was despite widespread
      improved drinking water source coverage (85.3%) and commonly self-reported
      boiling practices (82.2%). E.coli concentration levels in household drinking
      water were associated with wealth, education levels of a household head, and type
      of water source (i.e. vender water or local sources). Following the proposed SDG
      definition for Target 6.1 (water) and 6.2 (sanitation), the estimated proportion
      of households with access to safely managed drinking water and sanitation was
      8.5% and 45.5%, respectively in the study areas, indicating substantial
      difference from improved drinking water (82.2%) and improved sanitation coverage
      (70.9%) as per the MDGs targets. The greatest contamination and risk factors were
      found in the poorest households indicating the urgent need for targeted and
      effective interventions here. There is suggested evidence that sub-surface
      leaching from on-site sanitation adversely impacts on drinking water sources,
      which underscores the need for further technical assistance in promoting latrine
      construction. Urgent action is still needed to strengthen systematic monitoring
      efforts towards tracking SDG Goal 6.

PMID- 28743593
TI  - Should radiographic progression still be used as outcome in RA?
AB  - Radiographs of hands and feet are traditionally the images that are used to
      assess structural damage progression in drug trials in patients with rheumatoid
      arthritis, aiming at proving the disease modifying capacity of a drug. Although
      treatment has largely improved over the past decade and consequently radiographic
      progression is limited in control arms in clinical trials, recent trials are
      still able to show inhibition of structural progression by new drugs. The
      requirements for the successful use of radiographic progression as an outcome in
      rheumatoid arthritis trials will be discussed in this paper.

PMID- 28743594
TI  - Rhamnolipids as epithelial permeability enhancers for macromolecular
      therapeutics.
AB  - The use of surfactants as drug permeability enhancers across epithelial barriers
      remains a challenge. Although many studies have been performed in this field
      using synthetic surfactants, the possibility of employing surfactants produced by
      bacteria (the so called biosurfactants") has not been completely explored. Among
      them, one of the most well characterized class of biosurfactants are
      rhamnolipids. The aim of the study was to investigate the effect of rhamnolipids
      on the epithelial permeability of fluorescein isothiocyanate-labelled dextrans
      4kDa and 10kDa (named FD4 and FD10, respectively) as model for macromolecular
      drugs, across Caco-2 and Calu-3monolayers. These cell lines were selected as an
      in vitro model for the oral and respiratory administration of drugs. Before
      performing permeability studies, rhamnolipids mixture was analysed in terms of
      chemical composition and quantification through mass analysis and HPLC.
      Cytotoxicity and transepithelial electrical resistance (TEER) studies were also
      conducted using Caco-2 and Calu-3 cell lines. A dose-dependent effect of
      rhamnolipids on TEER and FD4 or FD10 permeability across both cell lines was
      observed at relatively safe concentrations. Overall, results suggest the
      possibility of using rhamnolipids as absorption enhancers for macromolecular
      drugs through a reversible tight junction opening (paracellular route), despite
      more investigations are required to confirm their mechanism of action in term of
      permeability.

PMID- 28743595
TI  - The film tells the story: Physical-chemical characteristics of IgG at the liquid
      air interface.
AB  - The presence of liquid-air interfaces in protein pharmaceuticals is known to
      negatively impact product stability. Nevertheless, the mechanisms behind
      interface-related protein aggregation are not yet fully understood. Little is
      known about the physical-chemical behavior of proteins adsorbed to the interface.
      Therefore, the combinatorial use of appropriate surface-sensitive analytical
      methods such as Langmuir trough experiments, Infrared Reflection-Absorption
      Spectroscopy (IRRAS), Brewster Angle Microscopy (BAM), and Atomic Force
      Microscopy (AFM) is highly expedient to uncover structures and events at the
      liquid-air interface directly. Concentration-dependent adsorption of a human
      immunoglobulin G (IgG) and characteristic surface-pressure/area isotherms
      substantiated the amphiphilic nature of the protein molecules as well as the
      formation of a compressible protein film at the liquid-air interface. Upon
      compression, the IgG molecules do not readily desorb but form a highly
      compressible interfacial film. IRRA spectra proved not only the presence of the
      protein at the interface, but also showed that the secondary structure does not
      change considerably during adsorption or compression. IRRAS experiments at
      different angles of incidence indicated that the film thickness and/or packing
      density increases upon compression. Furthermore, BAM images exposed the presence
      of a coherent but heterogeneous distribution of the protein at the interface.
      Topographical differences within the protein film after adsorption, compression
      and decompression were revealed using underwater AFM. The combinatorial use of
      physical-chemical, spectroscopic and microscopic methods provided useful insights
      into the liquid-air interfacial protein behavior and revealed the formation of a
      continuous but inhomogeneous film of native-like protein molecules whose
      topographical appearance is affected by compressive forces.

PMID- 28743596
TI  - The plasma contact system, a protease cascade at the nexus of inflammation,
      coagulation and immunity.
AB  - The contact system is a potent procoagulant and proinflammatory plasma protease
      cascade that is initiated by binding ("contact")-induced, auto-activation of
      factor XII zymogen. Formed active serine protease FXIIa then cleaves plasma
      prekallikrein to kallikrein that in turn liberates the mediator bradykinin from
      its precursor high molecular weight kininogen. Bradykinin induces inflammation
      with implications for host defense and innate immunity. FXIIa also triggers the
      intrinsic pathway of coagulation that has been shown to critically contribute to
      thrombosis. Vice versa, FXII deficiency impairs thrombosis in animal models
      without inducing abnormal excessive bleeding. Recent work has established the
      FXIIa-driven contact system as promising target for anticoagulant and anti
      inflammatory drugs. This review focuses on the biochemistry of the contact
      system, its regulation by endogenous and exogenous inhibitors, and roles in
      disease states. This article is part of a Special Issue entitled: Proteolysis as
      a Regulatory Event in Pathophysiology edited by Stefan Rose-John.

PMID- 28743597
TI  - Adaptive diversification between the classic rabbit hemorrhagic disease virus
      (RHDV) and the RHDVa isolates: A genome-wide perspective.
AB  - Rabbit haemorrhagic disease virus (RHDV) is a highly infectious pathogen that
      causes high mortality in wild and domestic rabbits. RHDV could be divided into
      two subtypes, classic RHDV and RHDVa, which present clear genetic, antigenic, and
      epidemiological differences. To further understand the nature of the diversity,
      we performed a genome-wide evolutionary study on the classic RHDV and RHDVa
      isolates. The results show that RHDV had experienced adaptive diversification
      with the dividing process of these subtypes. Furthermore, amino acid changes
      relevant to the adaptive diversification mainly cluster in viral capsid protein
      VP60. These results might be beneficial for a further understanding the function
      of VP60 and provide helpful hints for the genetic basis of RHDV emergence and re
      emergence.

PMID- 28743598
TI  - Decrease in endogenous brain allopregnanolone induces autism spectrum disorder
      (ASD)-like behavior in mice: A novel animal model of ASD.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder with core
      symptoms of social impairments and restrictive repetitive behaviors. Recent
      evidence has implicated a dysfunction in the GABAergic system in the
      pathophysiology of ASD. We investigated the role of endogenous allopregnanolone
      (ALLO), a neurosteroidal positive allosteric modulator of GABAA receptors, in the
      regulation of ASD-like behavior in male mice using SKF105111 (SKF), an inhibitor
      of type I and type II 5alpha-reductase, a rate-limiting enzyme of ALLO
      biosynthesis. SKF impaired sociability-related performance, as analyzed by three
      different tests; i.e., the 3-chamber test and social interaction in the open
      field and resident-intruder tests, without affecting olfactory function
      elucidated by the buried food test. SKF also induced repetitive grooming behavior
      without affecting anxiety-like behavior. SKF had no effect on short-term spatial
      working memory or long-term fear memory, but enhanced latent learning ability in
      male mice. SKF-induced ASD-like behavior in male mice was abolished by the
      systemic administration of ALLO (1mg/kg, i.p.) and methylphenidate (MPH:
      2.5mg/kg, i.p.), a dopamine transporter inhibitor. The effects of SKF on brain
      ALLO contents in male mice were reversed by ALLO, but not MPH. On the other hand,
      SKF failed to induce ASD-like behavior or a decline in brain ALLO contents in
      female mice. These results suggest that ALLO regulates episodes of ASD-like
      behavior by positively modulating the function of GABAA receptors linked to the
      dopaminergic system. Moreover, a sex-dependently induced decrease in brain ALLO
      contents may provide an animal model to study the main features of ASD.

PMID- 28743599
TI  - Cognitive behavioral therapy (CBT) for preventing Alzheimer's disease.
AB  - This review provides the rationale for implementing cognitive behavioral therapy
      (CBT) for the prevention of Alzheimer's disease (AD). There are known risk
      factors associated with the development of AD, some of which may be ameliorated
      with CBT. We posit that treating the risk factors of inactivity, poor diet,
      hyposmia and anosmia, sleep disorders and lack of regularly engaged challenging
      cognitive activity will modify the physiology of the brain sufficiently to avoid
      the accumulation of excess proteins, including amyloid beta, causal events in the
      development of AD. Further, the successful treatment of the listed risk factors
      is well within our technology to do so and, even further, it is cost effective.
      Also, there is considerable scientific literature to support the proposition
      that, if implemented by well-established practices, CBT will be effective and
      will be engaged by those of retirement age. That is, we present a biologically
      informed CBT for the prevention of the development of AD, i.e., an aspect of
      applied behavioral neuroscience.

PMID- 28743600
TI  - Sex determines effect of physical activity on diet preference: Association of
      striatal opioids and gut microbiota composition.
AB  - Previous studies suggest an interaction between the level of physical activity
      and diet preference. However, this relationship has not been well characterized
      for sex differences that may exist. The present study examined the influence of
      sex on diet preference in male and female Wistar rats that were housed under
      either sedentary (no wheel access) (SED) or voluntary wheel running access (RUN)
      conditions. Following a 1 week acclimation period to these conditions, standard
      chow was replaced with concurrent ad libitum access to a choice of 3 pelleted
      diets (high-fat, high-sucrose, and high-corn starch) in the home cage. SED and
      RUN conditions remained throughout the next 4 week diet preference assessment
      period. Body weight, running distance, and intake of each diet were measured
      daily. At the conclusion of the 4 week diet preference test, animals were
      sacrificed and brains were collected for mRNA analysis. Fecal samples were also
      collected before and after the 4 week diet preference phase to characterize
      microbiota composition. Results indicate sex dependent interactions between
      physical activity and both behavioral and physiological measures. Females in both
      RUN and SED conditions preferred the high-fat diet, consuming significantly more
      high-fat diet than either of the other two diets. While male SED rats also
      preferred the high-fat diet, male RUN rats consumed significantly less high-fat
      diet than the other groups, instead preferring all three diets equally. There was
      also a sex dependent influence of physical activity on both reward related opioid
      mRNA expression in the ventral striatum and the characterization of gut
      microbiota. The significant sex differences in response to physical activity
      observed through both behavioral and physiological measures suggest potential
      motivational or metabolic difference between males and females. The findings
      highlight the necessity for further exploration between male and female response
      to physical activity and feeding behavior.

PMID- 28743601
TI  - Reproductive factors and risk of Parkinson's disease in women: A meta-analysis of
      observational studies.
AB  - Evidence on the relationship between reproductive factors, use of oral
      contraceptives (OCs) and the incidence of Parkinson's disease (PD) remain
      inconclusive. The aim of this meta-analysis is to evaluate whether relevant
      reproductive factors including age at menarche, age at menopause, fertile
      lifespan, parity, type of menopause (surgical versus natural), and use of OCs are
      associated with risk of PD in women via random-effects model. PubMed and EMBASE
      database were used to search for case-control or cohort studies published before
      February17, 2017. 6 case-control and 5 cohort studies were included in the meta
      analysis. The pooled relative risks (RRs) of PD risk were 1.00 (95% CI: 0.79
      1.28) for use of OCs (ever versus never), 1.03 (95% CI: 0.84-1.26) for age at
      menarche, 0.98 (95% CI: 0.75-1.29) for age at menopause, 0.98(95% CI: 0.77-1.25)
      for fertile lifespan, 0.99(95% CI:0.0.79-1.25) for parity, 0.93 (95% CI:0.68
      1.29) for type of menopause (surgical versus natural). In the subgroup analysis
      stratified by study design, age, caffeine intake and smoking, an inverse
      association was found between surgical menopause and risk of PD for those
      adjusting for caffeine intake (RR: 0.67, 95% CI: 0.45-0.99) and smoking (RR:
      0.77, 95% CI: 0.63-0.94); while a positive association was found between surgical
      menopause and PD risk for those not adjusting for smoking (RR: 1.91, 95% CI: 1.29
      2.83). In conclusion, our meta-analysis provided little epidemiological support
      for the role of reproductive factors in the incidence of PD. Whether surgical
      menopause is inversely associated with the risk of PD requires further
      explorations.

PMID- 28743602
TI  - Menthol disrupts nicotine's psychostimulant properties in an age and sex
      dependent manner in C57BL/6J mice.
AB  - Menthol is a commonly used flavorant in tobacco and e-cigarettes, and could
      contribute to nicotine sensitivity. To understand how menthol could contribute to
      nicotine intake and addiction, it is important to determine whether specific
      mechanisms related to sex and age could underlie behavioral changes induced by
      menthol-laced nicotinic products. Using a validated paradigm of nicotine
      dependent locomotor stimulation, adolescent and adult C57BL/6J mice of both sexes
      were exposed to nicotine, or nicotine laced with menthol, as their sole source of
      fluid, and psychostimulant effects were evaluated by recording home cage
      locomotor activity for ten days. Nicotine and cotinine blood levels were measured
      following exposure. Results show an interaction between treatment, age, and sex
      on liquid consumption, indicating that mice responded differently to menthol and
      nicotine based on their age and sex. Adult male mice greatly increased their
      nicotine intake when given menthol. In female mice of both age groups, menthol
      did not have this effect. Despite an increase in nicotine intake promoted by
      menthol, adult male mice showed a significant decrease in locomotion, suggesting
      that menthol blunted nicotine-induced psychostimulation. This behavioral response
      to menthol was not detected in adolescent mice of either sex. These data confirm
      that menthol is more than a flavorant, and can influence both nicotine intake and
      its psychostimulant effects. These results suggest that age- and sex-dependent
      mechanisms could underlie menthol's influence on nicotine intake and that studies
      including adolescent and adult menthol smokers of both sexes are warranted.

PMID- 28743603
TI  - Pre- and post-natal melatonin administration partially regulates brain oxidative
      stress but does not improve cognitive or histological alterations in the Ts65Dn
      mouse model of Down syndrome.
AB  - Melatonin administered during adulthood induces beneficial effects on cognition
      and neuroprotection in the Ts65Dn (TS) mouse model of Down syndrome. Here, we
      investigated the effects of pre- and post-natal melatonin treatment on behavioral
      and cognitive abnormalities and on several neuromorphological alterations
      (hypocellularity, neurogenesis impairment and increased oxidative stress) that
      appear during the early developmental stages in TS mice. Pregnant TS females were
      orally treated with melatonin or vehicle from the time of conception until the
      weaning of the offspring, and the pups continued to receive the treatment from
      weaning until the age of 5 months. Melatonin administered during the pre- and
      post-natal periods did not improve the cognitive impairment of TS mice as
      measured by the Morris Water maze or fear conditioning tests. Histological
      alterations, such as decreased proliferation (Ki67+ cells) and hippocampal
      hypocellularity (DAPI+ cells), which are typical in TS mice, were not prevented
      by melatonin. However, melatonin partially regulated brain oxidative stress by
      modulating the activity of the primary antioxidant enzymes (superoxide dismutase
      in the cortex and catalase in the cortex and hippocampus) and slightly decreasing
      the levels of lipid peroxidation in the hippocampus of TS mice. These results
      show the inability of melatonin to prevent cognitive impairment in TS mice when
      it is administered at pre- and post-natal stages. Additionally, our findings
      suggest that to induce pro-cognitive effects in TS mice during the early stages
      of development, in addition to attenuating oxidative stress, therapies should aim
      to improve other altered processes, such as hippocampal neurogenesis and/or
      hypocellularity.

PMID- 28743604
TI  - Clinicopathological features, management and outcome of patients with poorly
      differentiated oral and oropharyngeal squamous cell carcinoma.
AB  - BACKGROUND: The purpose of this study was to explore the clinicopathological
      features, risk factors, and management of poorly differentiated oral and
      oropharyngeal squamous cell carcinoma (OOSCC) patients in the northern Chinese
      population. METHOD: A total of 118 poorly differentiated OOSCC patients from 2236
      consecutive cases were retrospectively enrolled in this study. RESULTS: Cox
      regression analysis showed that site (hazard ratio (HR): 2.561, 95% confidence
      interval (CI): 1.064-6.164, p = 0.036) and lymph node ratio (LNR) (HR: 3.915, 95%
      CI: 1.797-8.530, p = 0.001) were independent predictive factors for 5-year
      disease-specific survival (DSS). LNR >0.036, oropharynx site, and advanced
      clinical stage formulate a model of risk stratification. The patients with a risk
      score of >=2 were identified as the high-risk population, and patients with a
      risk score of 0 or 1 were identified as the low-risk population. Patients in the
      high-risk population who underwent surgery plus concurrent chemoradiotherapy
      (CCRT) had markedly better 5-year DSS than those who only underwent surgery
      (60.0% vs. 20.0%, p = 0.016). However, patients in the low-risk population who
      underwent surgery alone exhibited a similar 5-year DSS (68.2%) compared with
      those who received surgery plus radiotherapy (RT) (68.2%) or surgery plus CCRT
      (50.0%) (p = 0.907). CONCLUSIONS: High LNR, oropharynx site and advanced clinical
      stage constitute a model of risk stratification for patients with poorly
      differentiated OOSCC. If two or more risk factors are present, surgery and
      adjuvant chemoradiotherapy can give the best prognosis.

PMID- 28743605
TI  - Three-dimensional analysis of the pharyngeal airway space and hyoid bone position
      after orthognathic surgery.
AB  - PURPOSE: The aim of this study was to evaluate changes in the pharyngeal airway
      space (PAS) and hyoid bone position after orthognathic surgery with cone-beam
      computed tomography (CBCT). MATERIAL AND METHODS: This study was conducted with
      the tomographic records of 30 patients with skeletal class II or III deformities
      submitted to two different types of orthognathic surgery: Group 1 (n = 15),
      maxillary advancement, and mandibular setback; and Group 2 (n = 15),
      maxillomandibular advancement. CBCT scans were acquired preoperatively (T0); and
      at around 1.5 months (T1) and 6.7 months (T2) postoperatively. PAS volume,
      minimum cross-sectional area (min CSA), and hyoid bone position changes were
      assessed with Dolphin Imaging 3D software, and results analyzed with ANOVA and a
      Tukey-Kramer test (p < 0.05). RESULTS: The hyoid bone was significantly displaced
      in the horizontal dimension, moving posteriorly in Group 1, and anteriorly in
      Group 2. Although PAS volume and min CSA increased after both surgeries, these
      measurements were significantly larger only in Group 2. The significant
      differences that existed between groups preoperatively no longer existed after
      the surgeries. CONCLUSIONS: Both orthognathic surgeries assessed resulted in
      changes in hyoid bone position and increased PAS volume and min CSA, particularly
      after maxillomandibular advancement surgery.

PMID- 28743606
TI  - The Botanical Drug Substance Crofelemer as a Model System for Comparative
      Characterization of Complex Mixture Drugs.
AB  - Crofelemer is a botanical polymeric proanthocyanidin that inhibits chloride
      channel activity and is used clinically for treating HIV-associated secretory
      diarrhea. Crofelemer lots may exhibit significant physicochemical variation due
      to the natural source of the raw material. A variety of physical, chemical, and
      biological assays were used to identify potential critical quality attributes
      (CQAs) of crofelemer, which may be useful in characterizing differently sourced
      and processed drug products. Crofelemer drug substance was extracted from tablets
      of one commercial drug product lot, fractionated, and subjected to accelerated
      thermal degradation studies to produce derivative lots with variations in
      chemical and physical composition potentially representative of manufacturing and
      raw material variation. Liquid chromatography, UV absorbance spectroscopy, mass
      spectrometry, and nuclear magnetic resonance analysis revealed substantial
      changes in the composition of derivative lots. A chloride channel inhibition cell
      based bioassay suggested that substantial changes in crofelemer composition did
      not necessarily result in major changes to bioactivity. In 2 companion papers,
      machine learning and data mining approaches were applied to the analytical and
      biological data sets presented herein, along with chemical stability data sets
      derived from forced degradation studies, to develop an integrated mathematical
      model that can identify CQAs which are most relevant in distinguishing between
      different populations of crofelemer.

PMID- 28743607
TI  - Comparative Characterization of Crofelemer Samples Using Data Mining and Machine
      Learning Approaches With Analytical Stability Data Sets.
AB  - There is growing interest in generating physicochemical and biological analytical
      data sets to compare complex mixture drugs, for example, products from different
      manufacturers. In this work, we compare various crofelemer samples prepared from
      a single lot by filtration with varying molecular weight cutoffs combined with
      incubation for different times at different temperatures. The 2 preceding
      articles describe experimental data sets generated from analytical
      characterization of fractionated and degraded crofelemer samples. In this work,
      we use data mining techniques such as principal component analysis and mutual
      information scores to help visualize the data and determine discriminatory
      regions within these large data sets. The mutual information score identifies
      chemical signatures that differentiate crofelemer samples. These signatures, in
      many cases, would likely be missed by traditional data analysis tools. We also
      found that supervised learning classifiers robustly discriminate samples with
      around 99% classification accuracy, indicating that mathematical models of these
      physicochemical data sets are capable of identifying even subtle differences in
      crofelemer samples. Data mining and machine learning techniques can thus identify
      fingerprint-type attributes of complex mixture drugs that may be used for
      comparative characterization of products.

PMID- 28743608
TI  - Quantitative regional and sub-regional analysis of femoral and tibial subchondral
      bone mineral density (sBMD) using computed tomography (CT): comparison of non
      osteoarthritic (OA) and severe OA knees.
AB  - OBJECTIVE: This study aimed to compare subchondral bone mineral density (sBMD)
      between non-radiographic osteoarthritic (OA) and medial femorotibial OA knees,
      using computed tomography (CT). DESIGN: CT exams from 16 non-radiographic OA (KL
      grade < 2) and 16 severe medial OA (KL grade >= 3) knees (average age of 61.7 +/-
      3 and 62.2 +/- 5 years old respectively, 50% male in each group), were
      retrospectively analyzed. CT exams were segmented and 3D maps of sBMD based on
      the CT number in the most superficial 3 mm of femoral and tibial subchondral bone
      were computed. Average sBMD and medial-to-lateral sBMD ratios were calculated for
      total load-bearing regions and for sub-regions of interest in the femur and
      tibia. RESULTS: The analysis of total load-bearing regions did not reveal any
      significant difference between groups, except for the lateral tibia, where OA
      knees had lower sBMD. Sub-regional analysis unveiled differences with some sub
      regions of the femur and tibia presenting significantly lower (in the lateral
      compartment) or higher (in the medial compartment) sBMD in OA knees compared to
      non-OA knees. The M/L sBMD ratios were significantly higher for OA knees compared
      to non-OA knees for all regions and sub-regions, except for the internal sub
      regions. CONCLUSIONS: sBMD locally differs between non-OA and OA knees, in
      agreement with prior knowledge on biomechanics. CT proved to be a valuable tool
      for 3D analysis of femoral and tibial sBMD, which can be used in future studies
      to describe the chronology of sBMD alterations and improve our understanding of
      the role of subchondral bone in knee OA.

PMID- 28743609
TI  - Expression of CD73 slows down migration of skin dendritic cells, affecting the
      sensitization phase of contact hypersensitivity reactions in mice.
AB  - BACKGROUND: Application of haptens to the skin induces release of immune
      stimulatory ATP into the extracellular space. This "danger" signal can be
      converted to immunosuppressive adenosine (ADO) by the action of the
      ectonucleotidases CD39 and CD73, expressed by skin and immune cells. Thus, the
      expression and regulation of CD73 by skin derived cells may have crucial
      influence on the outcome of contact hypersensitivity (CHS) reactions. OBJECTIVE:
      To investigate the role of CD73 expression during 2,4,6-trinitrochlorobenzene
      (TNCB) induced CHS reactions. METHODS: Wild type (wt) and CD73 deficient mice
      were subjected to TNCB induced CHS. In the different mouse strains the resulting
      ear swelling reaction was recorded along with a detailed phenotypic analysis of
      the skin migrating subsets of dendritic cells (DC). RESULTS: In CD73 deficient
      animals the motility of DC was higher as compared to wt animals and in particular
      after sensitization we found increased migration of Langerin+ DC from skin to
      draining lymph nodes (LN). In the TNCB model this led to a stronger sensitization
      as indicated by increased frequency of interferon-gamma producing T cells in the
      LN and an increased ear thickness after challenge. CONCLUSION: CD73 derived ADO
      production slows down migration of Langerin+ DC from skin to LN. This may be a
      crucial mechanism to avoid over boarding immune reactions against haptens.

PMID- 28743610
TI  - Epidemiology and comorbidities of patients with chronic urticaria in Taiwan?: A
      nationwide population-based study.
AB  - BACKGROUND: Comprehensive data regarding the epidemiology of chronic urticaria
      (CU) in general populations are scant. OBJECTIVES: To investigate the prevalence,
      incidence, and comorbidities of CU in general population. METHODS: The data were
      sourced from the National Health Insurance Research Database (NHIRD) for 2009
      2012. Patients who had a primary/secondary ICD-9-CM diagnosis code of 708.1,
      708.8, or 708.9 during the year with at least two outpatient visits and an
      antihistamine prescription, were identified as the cases of CU for each year. The
      incidence, persistence and comorbidities of CU were examined. RESULTS: The
      prevalence of CU ranged from 0.69% to 0.79% for each year from 2009 to 2012, and
      the incidence was around 0.50% per year from 2010 to 2012. Comparing to the
      Standard Population, the standardized prevalence ratios (SPRs) for the rheumatic
      diseases, thyroid disorders, inflammatory diseases, and psychiatric disorders
      among CU patients were 2.74, 1.81, 1.57 and 1.87, respectively. CONCLUSION: The
      prevalence of CU in Taiwan is about 0.69-0.79%. CU is associated with a
      significantly increased risk of psychiatric disorders, inflammatory diseases,
      thyroid disorders, and rheumatic diseases. Except for thyroid disorders, the
      prevalence of these comorbidities tends to increase the longer CU persists.

PMID- 28743611
TI  - Increased frequencies of basophils, type 2 innate lymphoid cells and Th2 cells in
      skin of patients with atopic dermatitis but not psoriasis.
AB  - BACKGROUND: Pathogenesis of atopic dermatitis (AD) involves interaction between
      type 2 cells that include basophils, mast cells, innate lymphoid type 2 cells
      (ILC2), and Th2 cells. Levels of IL-4 and IL-13 are elevated in AD patients.
      OBJECTIVE: Here, we investigated the distribution of type 2 cells and the source
      of IL-4 and IL-13 in skin and blood of AD relative to psoriasis. METHODS:
      Lesional skin biopsies and blood were collected from patients. Skin cell
      suspensions were prepared by mild enzymatic digestion and mechanical
      dissociation. IL-4 and IL-13 expression was analyzed at single-cell level before
      or after stimulation using flow cytometry. RESULTS: Frequencies of basophils,
      ILC2 and Th2 but not mast cells were significantly elevated in skin, and not
      blood, of AD relative to psoriasis. IL-4 production by circulating basophils and
      Th2 cells, and IL-13 by ILCs and Th2 cells was similar in both diseases. In
      contrast, skin T cells expressed IL-4 and IL-13 prior to stimulation in AD when
      compared to psoriasis. Moreover, skin basophils, which were detected in AD only,
      expressed IL-4 following stimulation. Interestingly, basophils and ILC2 were
      positively correlated in skin, whereas skin basophils were inversely correlated
      with blood ILC2. CONCLUSIONS: Lesional AD skin harbors a distinctive innate and
      adaptive type 2 profile, which is characterized by basophils producing IL-4, Th2
      cells expressing IL-4 or IL-13, and ILC2. This underlies the therapeutic efficacy
      of targeting IL-4 and IL-13 signaling pathways in AD.

PMID- 28743612
TI  - Clinical outcomes after interstitial brachytherapy for early-stage nasal squamous
      cell carcinoma.
AB  - PURPOSE: Radiotherapy of nasal carcinomas results in cure rates comparable to
      surgery, with anatomic preservation and good cosmesis. Brachytherapy (BT)
      overcomes difficulties with dosimetric coverage and affords a localized and
      highly conformal irradiation. We report our experience of BT for early-stage
      nasal squamous cell carcinomas (SCCs). METHODS AND MATERIALS: Clinical data, BT
      parameters, and outcome of consecutive patients treated by interstitial BT in our
      institute between December 1982 and April 2015 for a localized nasal SCC were
      examined. A total of 34 patients with newly diagnosed T1-2N0-1 nasal skin (n =
      22) or nasal cavity (n = 12) SCC were identified. Implantation and dosimetry were
      done according to the Paris system rules. Low-dose-rate (n = 30) or pulsed-dose
      rate (n = 4) techniques were used. Median dose was 70 Gy (64-75 Gy). Sites of
      tumor recurrence, toxicity rates, and cosmesis outcome were examined. RESULTS:
      Median followup time was 89 months. All patients achieved complete response. Five
      patients experienced local failure, with a median interval of 9 months (range, 5
      12 months). Grade 3 acute reactions were reported in 2 patients (6%). Most
      delayed complications were mild to moderate, and good or fair cosmesis was
      achieved in 97%. Estimated local failure-free survival and disease-free survival
      rates at 5 year were 85% (95% CI = 68-94%) and 76% (95% CI = 58-88%),
      respectively. CONCLUSIONS: Interstitial BT is effective for selected nasal SCCs,
      with durable local control, acceptable toxicity, and good cosmesis.

PMID- 28743613
TI  - Ethanol prefermentation of food waste in sequencing batch methane fermentation
      for improved buffering capacity and microbial community analysis.
AB  - This study investigates the effects of ethanol prefermentation (EP) on methane
      fermentation. Yeast was added to the substrate for EP in the sequencing batch
      methane fermentation of food waste. An Illumina MiSeq high-throughput sequencing
      system was used to analyze changes in the microbial community. Methane production
      in the EP group (254mL/g VS) was higher than in the control group (35mL/g VS)
      because EP not only increased the buffering capacity of the system, but also
      increased hydrolytic acidification. More carbon source was converted to ethanol
      in the EP group than in the control group, and neutral ethanol could be converted
      continuously to acetic acid, which promoted the growth of Methanobacterium and
      Methanosarcina. As a result, the relative abundance of methane-producing bacteria
      was significantly higher than that of the control group. Kinetic modeling
      indicated that the EP group had a higher hydrolysis efficiency and shorter lag
      phase.

PMID- 28743614
TI  - Sustainable pollutant removal by periphytic biofilm via microbial composition
      shifts induced by uneven distribution of CeO2 nanoparticles.
AB  - The responses of periphytic biofilm to CeO2 nanoparticle (CNP) exposure were
      explored by investigating community shifts and pollutant removal. Results showed
      that CNPs entered the sensitive microbial cells in the periphytic biofilm,
      leading to cytomembrane damage and intracellular reactive oxygen species (ROS)
      generation. The periphytic biofilm communities were, however, able to adapt to
      the prolonged exposure and maintain their pollutant removal (i.e., phosphorus,
      nitrogen and copper, organic matter) performance. Observations under synchrotron
      radiation scanning transmission X-ray microscopy revealed that fewer CNPs were
      distributed in algal cells compared to bacterial cells, wherein the
      transformation between Ce(IV) and Ce(III) occurred. High-throughput sequencing
      further showed that the proportion of algae, such as Leptolyngbya and Nostoc,
      significantly increased in the periphytic biofilm exposed to CNPs while the
      proportion of bacteria, such as Bacilli and Gemmatimonadetes, decreased. This
      change in community composition might be the primary reason for the sustained
      pollutant removal performance of the periphytic biofilm.

PMID- 28743615
TI  - Experimental study of cyclone pyrolysis - Suspended combustion air gasification
      of biomass.
AB  - Based on the original biomass cyclone gasifier, the cyclone pyrolysis-suspension
      combustion gasification technology was constituted with a bottom wind ring to
      build the biochar suspension combustion zone. This technology decouples the
      biomass pyrolysis, gasification (reduction reaction) and combustion (oxidation
      reaction) within the same device. With the feed amount and total air fixed, the
      effect of air rate arrangement on temperature distribution of the gasifier,
      syngas components and gasification parameters was studied. With the secondary air
      rate (0.20) and bottom air rate (0.50), the gasification efficiency was best,
      with gas heating value of 5.15MJ/Nm3, carbon conversion rate of 71.50%,
      gasification efficiency of 50.80% and syngas yield of 1.29Nm3/kg. The device with
      biochar for the tar catalytic cracking was installed at the gasifier outlet,
      effectively reducing the tar content in syngas, with a minimum value of
      1.02g/Nm3.

PMID- 28743616
TI  - Heart position variability during voluntary moderate deep inspiration breath-hold
      radiotherapy for breast cancer determined by repeat CBCT scans.
AB  - Voluntary moderate deep inspiration breath hold (vmDIBH) in left-sided breast
      cancer radiotherapy reduces cardiac dose. The aim of this study was to
      investigate heart position variability in vmDIBH using CBCT and to compare this
      variability with differences in heart position between vmDIBH and free breathing
      (FB). For 50 patients initial heart position with respect to the field edge (HP
      FE) was measured on a vmDIBH planning CT scan. Breath-hold was monitored using an
      in-house developed vertical plastic stick. On pre-treatment CBCT scans, heart
      position variability with respect to the field edge (DeltaHP-FE) was measured,
      reflecting heart position variability when using an offline correction protocol.
      After registering the CBCT scan to the planning CT, heart position variability
      with respect to the chest wall (DeltaHP-CW) was measured, reflecting heart
      position variability when using an online correction protocol. As a control
      group, vmDIBH and FB computed tomography (CT) scans were acquired for 30 patients
      and registering both scans on the chest wall. For 34 out of 50 patients, the
      average HP-FE and HP-CW increased over the treatment course in comparison to the
      planning CT. Averaged over all patients and all treatment fractions, the DeltaHP
      FE and the DeltaHP-CW was 0.8+/-4.2mm (range -9.4-+10.6mm) and 1.0+/-4.4mm (range
      -8.3-+10.4mm) respectively. The average gain in heart to chest wall distance was
      11.8+/-4.6mm when using vmDIBH instead of FB. In conclusion, substantial
      variability in heart position using vmDIBH was observed during the treatment
      course.

PMID- 28743617
TI  - Can the Day 0 CT-scan predict the post-implant scanning? Results from 136
      prostate cancer patients.
AB  - PURPOSE: Post-implant CT-scanning is an essential part of permanent prostate
      brachytherapy. However, the evaluation of post-implant CT dosimetry is not
      straightforward due to the edema that can modify the dose to the prostate and to
      the organs at risk. The aim of this study is to evaluate the impact of the timing
      of the post-implant CT-scan on the dosimetric results and to verify if the Day 0
      scan findings can predict Day 50 scanning. METHODS: 136 consecutive patients who
      received monotherapy with I-125 implants were selected for this study. Two sets
      of 8 dosimetric quality parameters corresponding to 2 different CT-scans (Day 0
      and Day 50) were calculated and compared. The dosimetric parameters included are
      the percentage volume of the post-implant prostate receiving 80%, 100% and 150%
      of the prescribed dose, the doses covering 80% and 90% of the prostate volume and
      the Dose Homogeneity Index. The values of the dose covering 1cm3 of the rectum
      and urethra were assessed. RESULTS: All the dosimetric parameters of the Day 50
      were higher than those of the Day 0 scan. Linear functions were obtained that
      calculate D90 and V100 values at Day 50 based on the Day 0 findings. Rectal and
      urethral parameters tended to be underestimated on Day 0 CT-scan relative to Day
      50 based dosimetry. CONCLUSIONS: Predicting the Day 50 dosimetry from the Day 0
      scan could be a possible alternative to a Day 50 scan only in specific
      situations, but with a degree of uncertainty in the predicted values.

PMID- 28743618
TI  - Deep architecture neural network-based real-time image processing for image
      guided radiotherapy.
AB  - INTRODUCTION: To develop real-time image processing for image-guided
      radiotherapy, we evaluated several neural network models for use with different
      imaging modalities, including X-ray fluoroscopic image denoising. METHODS &
      MATERIALS: Setup images of prostate cancer patients were acquired with two
      oblique X-ray fluoroscopic units. Two types of residual network were designed: a
      convolutional autoencoder (rCAE) and a convolutional neural network (rCNN). We
      changed the convolutional kernel size and number of convolutional layers for both
      networks, and the number of pooling and upsampling layers for rCAE. The ground
      truth image was applied to the contrast-limited adaptive histogram equalization
      (CLAHE) method of image processing. Network models were trained to keep the
      quality of the output image close to that of the ground-truth image from the
      input image without image processing. For image denoising evaluation, noisy input
      images were used for the training. RESULTS: More than 6 convolutional layers with
      convolutional kernels >5*5 improved image quality. However, this did not allow
      real-time imaging. After applying a pair of pooling and upsampling layers to both
      networks, rCAEs with >3 convolutions each and rCNNs with >12 convolutions with a
      pair of pooling and upsampling layers achieved real-time processing at 30 frames
      per second (fps) with acceptable image quality. CONCLUSIONS: Use of our suggested
      network achieved real-time image processing for contrast enhancement and image
      denoising by the use of a conventional modern personal computer.

PMID- 28743619
TI  - Organ and effective doses from paediatric interventional cardiology procedures in
      Chile.
AB  - The aim of this study was to present the results of organ and effective doses for
      paediatric patients for different types of interventional cardiology procedures
      for age and weight groups, derived from a patient dosimetry pilot programme
      carried out in Chile, under the auspices of the International Atomic Energy
      Agency. Over seven years, a retrospective collection of demographic and patient
      dose data was obtained: age, gender, weight, height, number of cine series, total
      number of cine frames, fluoroscopy time, dose-area product (DAP) and cumulative
      dose at patient entrance reference point. Monte Carlo software was used to
      calculate organ and effective doses. 1506 procedures were divided into four age
      and seven weight groups. Organ doses (median values) for diagnostic and
      therapeutic procedures were: active bone marrow 0.90 and 0.64mGy; heart 1.99 and
      1.46mGy; lungs 3.56 and 2.59mGy; thyroid 1.27 and 0.83; and breast (in the case
      of females) 1.78 and 1.36mGy. The ranges for effective doses (median values) and
      weight bands were 1.2-3.9mSv for diagnostic procedures and 1.0-2.5mSv for
      therapeutic procedures. The resulting conversion factors (median values) to
      estimate effective dose from DAP (in mSv/Gy.cm2) were: 1.70; 0.89; 0.58; and
      0.40, for age groups of <1year, 1-<5years, 5-<10years and 10-<16years,
      respectively. The obtained set of dose values will enable comparisons with other
      imaging procedures (comparing the same age bands) for justification and
      optimization purposes.

PMID- 28743620
TI  - Reviewing the functional basis of the syntactic Merge mechanism for language: A
      coordinate-based activation likelihood estimation meta-analysis.
AB  - The ability to create structures out of single words is a key aspect of human
      language. This combinatorial capacity relies on a low-level syntactic mechanism
      Merge-assembling words into hierarchies. Neuroscience has explored Merge by
      comparing syntax to word-lists. Here, we first review potential issues with the
      word-lists materials. We then perform an activation likelihood estimation (ALE)
      on the reported foci, to reveal functional convergence for Merge at whole-brain
      level. Finally, we run probabilistic tractography on an independent population to
      observe how these convergent activations anatomically connect. Functionally, we
      found that when confounding activity was removed, consistency for Merge was only
      observable in the left pars opercularis (BA44) and in the inferior part of the
      posterior superior temporal sulcus/gyrus (pSTS/STG; BA22). Structurally, we could
      confirm that the two regions are connected through dorsal fiber bundles. We
      therefore suggest that the cortical implementation of linguistic Merge consists
      of a left fronto-temporal interaction between BA44 (syntactic processor) and
      pSTS/STG (integrative processor), which communicate to each other along dorsal
      white matter fascicles.

PMID- 28743621
TI  - MHC Class I Cross-Presentation: Stage Lights on Sec22b.
AB  - Efficient (cross-)presentation of antigens internalized by dendritic cells (DCs)
      requires vesicular communication between the early secretory and the
      endocytic/phagocytic pathways, in which the Sec22b protein has been suggested to
      have a key role. Here, we undertake a critical assessment of two new studies that
      evaluate the role of Sec22b using gene-targeted mice and come to contradictory
      conclusions.

PMID- 28743622
TI  - Identification and characterization of atypical 2-cysteine peroxiredoxins from
      mud crab Scylla paramamosain: The first evidence of two peroxiredoxin 5 genes in
      non-primate species and their involvement in immune defense against pathogen
      infection.
AB  - Peroxiredoxin 5 (Prx5) belongs to a novel family of evolutionarily conserved
      antioxidant proteins that protect cells against various oxidative stresses.
      Generally, no more than one Prx5 transcript had been reported in non-primate
      species. In this study, two Prx5 genes (coined as SpPrx5-1 and SpPrx5-2) were
      firstly isolated from the mud crab, Scylla paramamosain, through RT-PCR and RACE
      methods. The open reading frame of SpPrx5-1 and SpPrx5-2 were 561 bp and 429 bp
      in length, encoding 186 and 142 amino acids polypeptide, respectively. Both the
      conserved signatures of peroxiredoxin catalytic center and Prx5-specific domain
      were identified in SpPrx5-1 and SpPrx5-2. Phylogenetic analysis indicated that
      both SpPrx5 clustered together with other animal Prx proteins and were classified
      into Prx5 subfamily. Tissue-specific expression analysis revealed that both
      SpPrx5-1 and SpPrx5-2 were ubiquitously expressed, highest in hepatopancreas, and
      showed remarkably similar transcription patterns. Quantitative RT-PCR analysis
      exhibited that both SpPrx5 genes changed dramatically in hepatopancreas, although
      showing different expression profiles, after virus-analog poly (I:C) or Vibrio
      alginolyticus challenge. The expression levels of both SpPrx5s were significantly
      enhanced in hepatopancreas after poly (I:C) stimulation, while SpPrx5-2 exhibited
      a more prompt response than SpPrx5-1. Nevertheless, the expression levels of both
      SpPrx5s were significantly reduced in hepatopancreas after Vibrio alginolyticus
      challenge in which SpPrx5-1 showed a more prompt response than SpPrx5-2. These
      results suggested the involvement of SpPrx5s in responses against viral and
      bacterial infections and further highlighted their functional importance in the
      immune system of Scylla paramamosain.

PMID- 28743623
TI  - Novel mannose binding natterin-like protein in the skin mucus of Atlantic cod
      (Gadus morhua).
AB  - This study presents the first report of purification of natterin-like protein
      (Nlp) in a non-venomous fish. The peptide identities of purified cod Nlp were
      confirmed through LC-MSMS and matched to a cod expressed sequence tag (EST). A
      partial cod nlp nucleotide sequence was amplified and sequenced based on this
      EST. Multiple sequence alignment of cod Nlp showed considerable homology with
      other teleost Nlps and the presence of an N-terminal jacalin-like lectin domain
      coupled with a C-terminal toxin domain. nlp expression was higher in skin, head
      kidney, liver and spleen than in other tissues studied. Hemaggluttination of
      horse red blood cells by Nlp was calcium dependent and inhibited by mannose. A
      Vibrio anguillarum bath challenge however, did not alter the expression of cod
      nlp transcripts in the skin and gills. Further functional characterization is
      required to establish the significance of this unique protein in Atlantic cod and
      other teleosts.

PMID- 28743624
TI  - Russian sturgeon cultured in a subtropical climate shows weaken innate defences
      and a chronic stress response.
AB  - Russian sturgeon (Acipenser gueldenstaedtii) has been successfully farmed in
      Uruguay for the past ten years. However, during the Uruguayan summer fish endure
      high water temperatures and increased bacterial infections that threaten
      aquaculture. Our understanding of sturgeon's immune system and its interplay with
      environmental factors like temperature is almost unknown. This study analysed the
      way in which seasonal variations affect enzymatic blood components of Russian
      sturgeon's innate defences, including the serum alternative complement pathway
      (ACP), ceruloplasmin (Cp) and lysozyme activities. Results showed that summertime
      conditions in the farm altered these defences in different ways, inducing a
      significant decrease in ACP and Cp, and an increase in lysozyme. In addition,
      serum levels of total protein and cortisol decreased in summer, suggesting a
      chronic stress response was induced in parallel. Subsequently, we analysed
      whether the increase in water river temperature during summer could account for
      the observed results. To that end, we acclimated juvenile sturgeons to mild (18 
      degrees C) or warm (24  degrees C) temperatures for 37 days. Like in summer,
      sturgeons exposed to 24  degrees C showed lower levels of serum ACP, Cp and total
      proteins, together with a progressive decrease in body weight and increased fish
      mortality. Administration of an immunostimulant containing Se and Zn slightly
      reverted the temperature-induced effects on sturgeon's defences. Altogether, our
      study provides novel data on various physiological parameters of the Russian
      sturgeon and highlights the impact warm temperature has on stress and innate
      immunity in this chondrostean fish.

PMID- 28743625
TI  - A single WAP domain-containing protein from Litopenaeus vannamei possesses
      antiproteinase activity against subtilisin and antimicrobial activity against
      AHPND-inducing Vibrio parahaemolyticus.
AB  - The single WAP domain-containing protein (SWD) is a type III crustin
      antimicrobial peptide whose function is to defense the host animal against the
      bacterial infection by means of antimicrobial and antiproteinase activities. A
      study of SWD from Litopenaeus vannamei (LvSWD) is reported herein about its
      activities and function against bacteria, particularly the AHPND-inducing Vibrio
      parahaemolyticus (VPAHPND) that causes acute hepatopancreatic necrosis disease
      (AHPND). The LvSWD is mainly synthesized in hemocytes and up-regulated in
      response to VPAHPND infection. Over-expressed mature recombinant LvSWD (rLvSWD)
      and its WAP domain (rLvSWD-WAP) are able to strongly inhibit subtilisin but not
      trypsin, chymotrypsin and elastase. The rLvSWD inhibits subtilisin with the
      inhibition constant (Ki) of 14.3 nM. However, only rLvSWD exhibited antimicrobial
      activity against both Gram-positive and Gram-negative bacteria. Unlike the
      rLvSWD, the rLvSWD-WAP does not possess antimicrobial activity. Therefore, the
      killing effect of rLvSWD on VPAHPND and Bacillus megaterium was studied. The MIC
      of 30 MUM against VPAHPND is bactericidal whereas the MIC against B. megaterium
      is not. With four times the MIC of rLvSWD, the VPAHPND-treated post larval shrimp
      are able to survive longer with 50% survival rate as long as 78 h as compared to
      36 h of the infected shrimp without rLvSWD. The antimicrobial activity of LvSWD
      against the VPAHPND infection suggests its potential application for disease
      control in aquaculture.

PMID- 28743626
TI  - The roles of NF-kappaB and ROS in regulation of pro-inflammatory mediators of
      inflammation induction in LPS-stimulated zebrafish embryos.
AB  - In this study, the roles of reactive oxygen species (ROS) and NF-kappaB on
      inflammation induction in lipopolysaccharide (LPS)-stimulated zebrafish embryos
      were evaluated using N-acetyl-l-cysteine (NAC) and pyrrolidine dithiocarbamate
      (PDTC), specific inhibitors of ROS and NF-kappaB, respectively. LPS-stimulated
      zebrafish embryos showed increasing production of NO and ROS and expression of
      iNOS and COX-2 protein, compared to a control group without LPS. However, NAC
      significantly inhibited production of NO and ROS and markedly suppressed
      expression of iNOS and COX-2 protein in LPS-stimulated zebrafish embryos. The
      mRNA expressions of NF-kappaB such as p65NF-kappaB and IkappaB-A were
      significantly increased after LPS stimulation, whereas PDTC attenuated mRNA
      expression of NF-kappaB. PDTC also inhibited production of NO and reduced
      expression of iNOS and COX-2 protein in LPS-stimulated zebrafish embryos. Taken
      together, these results indicated that LPS increases pro-inflammatory mediators
      in zebrafish embryos through ROS and NF-kappaB regulation.

PMID- 28743627
TI  - Characterization of a novel non-receptor tyrosine kinase Src from Litopenaeus
      vannamei and its response to white spot syndrome virus infection.
AB  - Src family kinases (SFKs), a class of non-receptor tyrosine kinases, mediate a
      wide aspect of cellular signaling pathways that regulate cell proliferation,
      differentiation, motility and survival. In this study, we identified and
      characterized for the first time a novel SFK homologue from Litopenaeus vannamei
      (designated as LvSrc). Sequence analysis showed that LvSrc had a high homology
      with the identified SFKs, especially those from invertebrates. LvSrc contained
      the conserved SH3, SH2 and tyrosine kinase domains, as well as the potential
      phosphorylation and lipid modification sites. Immunofluorescence analysis
      demonstrated that LvSrc was mostly localized at the plasma membrane and partly
      resided in the perinuclear vesicle and nucleus or whole cell. Infection with
      white spot syndrome virus (WSSV) could up-regulate the transcription and
      expression levels of LvSrc and further induced its phosphorylation, suggesting
      that LvSrc was implicated in WSSV infection. Furthermore, our co
      immunoprecipitation result confirmed the interaction between Src and focal
      adhesion kinase (FAK) in shrimp, while the phosphorylation of FAK was markedly
      enhanced by co-expression with LvSrc. In sum, our studies suggested that LvSrc
      might act in the FAK-regulated signaling pathway during WSSV infection, which
      would give us a better insight in understanding the role of SKFs in host-virus
      interactions in crustaceans.

PMID- 28743628
TI  - Manganese-superoxide dismutase (MnSOD), a role player in seahorse (Hippocampus
      abdominalis) antioxidant defense system and adaptive immune system.
AB  - Manganese superoxide dismutase (MnSOD) is a metaloenzyme that catalyzes
      dismutation of the hazardous superoxide radicals into less hazardous H2O2 and
      H2O. Here, we identified a homolog of MnSOD from big belly seahorse (Hippocampus
      abdominalis; HaMnSOD) and characterized its structural and functional features.
      HaMnSOD transcript possessed an open reading frame (ORF) of 672 bp which codes
      for a peptide of 223 amino acids. Pairwise alignment showed that HaMnSOD shared
      highest identity with rock bream MnSOD. Results of the phylogenetic analysis of
      HaMnSOD revealed a close proximity with rock bream MnSOD which was consistent
      with the result of homology alignment. The intense expression of HaMnSOD was
      observed in the ovary, followed by the heart and the brain. Further, immune
      related responses of HaMnSOD towards pathogenic stimulation were observed through
      bacterial and viral challenges. Highest HaMnSOD expression in response to
      stimulants Edwardsiella tarda, Streptococcus iniae, lipopolysaccharide (LPS), and
      polyinosinic-polycytidylic acid (Poly I:C) was observed in the late stage in the
      blood tissue. Xanthine/xanthine oxidase assay (XOD assay) indicated the ROS
      scavenging ability of purified recombinant HaMnSOD (rHaMnSOD). The optimum
      conditions for the SOD activity of rHaMnSOD were pH 9 and the 25  degrees C.
      Collectively, the results obtained through the expressional analysis profiles and
      the functional assays provide insights into potential immune related and
      antioxidant roles of HaMnSOD in the big belly seahorse.

PMID- 28743629
TI  - Administration of a polyphenol-enriched feed to farmed sea bass (Dicentrarchus
      labrax L.): Kidney melanomacrophages response.
AB  - The reinforcement of the defense mechanism of fish, through the administration of
      immunostimulants, is considered as a promising alternative to vaccines. Natural
      immunostimulants such as polyphenols, flavanoids, pigments and essential oils can
      modulate the innate immune response. In lower vertebrates, melano-macrophage
      centres, i.e. clusters of pigment-containing cells forming the extracutaneous
      pigment system, are wide-spread in the stroma of the haemopoietic tissue, mainly
      in kidney and spleen. In fishes, melano-macrophage centres play an important role
      in the immune response against antigenic stimulants and pathogens. In the present
      study, we evaluated the effect of a polyphenol-enriched diet on the health status
      of European sea bass (Dicentrarchus labrax L.). Farmed sea bass were administered
      a feed containing a phytocomplex, rich in catechins and epigallocatechins, which
      was obtained from the seeds of Canosina Nero di Troia Vitis vinifera and mixed
      with conventional feed at two different concentrations. The effects of such a
      diet were investigated in juvenile and commercial size samples, i.e. undergoing a
      short- and long-term period of diet, respectively, focusing on their
      extracutaneous pigmentary system and, in more detail, on the enzymatic activities
      leading to melanin biosynthesis. Our results show that prolonged dietary
      treatments with higher concentration of polyphenols might modulate tyrosinase
      activity and gene expression in commercial size fishes. An increase of melano
      macrophage activity is correlated to a stimulation of cytoprotective functions
      against antigenic stimulants and pathogens, as an expression of a robust and
      protective adaptive immune response.

PMID- 28743630
TI  - Effect of Cucurbita mixta (L.) seed meal enrichment diet on growth, immune
      response and disease resistance in Oreochromis mossambicus.
AB  - The impact of Cucurbita mixta (L.) seed meal enriched diet on growth performance,
      innate immune response, and disease resistance in Oreochromis mossambicus against
      Aeromonas hydrophila was investigated. O. mossambicus was fed with 2 g kg-1, 4 g
      kg-1, and 6 g kg-1 C. mixta seed meal diets for a period of 4 weeks. The results
      indicated that C. mixta seed meal diets at 4 g kg-1 and 6 g kg-1 significantly (P
      < 0.05) enhances the survival rate, weight gain (WG), protein efficiency ratio
      (PER), specific growth rate (SGR), feed conversion ratio (FCR), and feed
      efficiency (FE) from weeks 1-4 when compared to control. C. mixta seed meals
      administered as feed supplements significantly (P < 0.05) enhanced the complement
      activity, phagocytic activity, respiratory burst activity, and lysosome activity
      in infected fish fed with 4 g kg-1 and 6 g kg-1 of C. mixta seed meal enriched
      diet from weeks 2-4. The cumulative mortality was lower in the fish fed with 4 g
      kg-1 and 6 g kg-1 of C. mixta seed meal enriched diets (15% and 18%) than with 2
      g kg-1 diet (26%). The present investigation suggested that C. mixta seed meal
      enriched diet at 4 g kg-1 and 6 g kg-1 enhance the better growth performance,
      innate immunity, and disease resistance against A. hydrophilla in O. mossambicus.

PMID- 28743631
TI  - Molecular characterization and functional analysis of the hepcidin gene from
      roughskin sculpin (Trachidermus fasciatus).
AB  - Hepcidin is a kind of cysteine-rich antimicrobial peptide that plays a vital role
      in host innate immune activity and iron regulation. Here, we report the molecular
      characterization and functional analysis of a novel hamp1 hepcidin isoforms Tf
      Hep from roughskin sculpin, Trachidermus fasciatus. A cDNA fragment of 988 bp
      with an ORF of 273 bp was obtained. The coding sequence encodes for a signal
      peptide of 24 amino acids coupled with a prodomain of 40 amino acids and a mature
      peptide of 26 amino acids. Tissue distribution analysis indicated that Tf-Hep was
      most abundant in the liver. It could be significantly induced post
      lipopolysaccharide (LPS) challenge and heavy metal exposure. The mature peptide
      was expressed as a 6.061 kDa fusion protein in Pichia pastoris GS115. The active
      purified recombinant protein (rTf-Hep) exhibited a wide spectrum of potent
      antimicrobial activity in vitro against 4 Gram-negative bacteria Escherichia
      coli, Vibrio Anguillarum, Klebsiella pneumoniae, and Pseudomonas aeruginosa and 4
      Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, Bacillus
      thuringiensis, and Bacillus megaterium with minimum inhibitory concentrations
      (MICs) of 5-80 MUg/ml (0.825-13.2 MUM). It also displayed high affinity to
      polysaccharides on bacteria surface including LPS, lipoteichoic acid (LTA) and
      peptidoglycan (PGN). We further revealed that rTf-hep was capable of
      agglutinating 6 of the 8 bacteria. All these results suggest that rTf-hep may be
      both an antibacterial effector and a pattern recognition molecule in fish immune
      defense. The in vivo bacterial treatment results demonstrated that rTf-Hep could
      significantly improve the survival rate of fish infected with V. anguillarum.
      Taken together, these data indicate an important role for Tf-hep in the innate
      immunity of Trachidermus fasciatus and suggest its potential application in
      aquaculture for increasing fish resistance to disease.

PMID- 28743632
TI  - Comparative analysis of dual specificity protein phosphatase genes 1, 2 and 5 in
      response to immune challenges in Japanese flounder Paralichthys olivaceus.
AB  - Dual-specificity MAP kinase (MAPK) phosphatases (DUSPs) are well-established
      negative modulators in regulating MAPK signaling in mammalian cells and tissues.
      Our previous studies have shown the involvement of DUSP6 in regulating innate
      immunity in Japanese flounder Paralichthys olivaceus. In order to gain a better
      understanding of the role of DUSPs in fish innate immunity, in the present study
      we identified and characterized three additional DUSP genes including DUSP1, 2
      and 5 in P. olivaceus. The three Japanese flounder DUSP proteins share common
      domain structures composed of a conserved N-terminal Rhodanase/CDC25 domain and a
      C-terminal catalytic phosphatase domain, while they show only less than 26%
      sequence identities, indicating that they may have different substrate
      selectivity. In addition, mRNA transcripts of all the three DUSP genes are
      detected in all examined Japanese flounder tissues; however, DUSP1 is dominantly
      expressed in spleen while DUSP2 and 5 are primarily expressed in skin.
      Furthermore, all the three DUSP genes are constitutively expressed in the
      Japanese flounder head kidney macrophages (HKMs) and peripheral blood leucocytes
      (PBLs) with unequal distribution patterns. Moreover, all the three DUSPs gene
      expression was induced differently in response to the LPS and double-stranded RNA
      mimic poly(I:C) stimulations both in the Japanese flounder HKMs and PBLs,
      suggesting an association of DUSPs with TLR signaling in fish. Taken together,
      the co-expression of various DUSPs members together with their different
      responses to the immune challenges indicate that the DUSP members may operate
      coordinately in regulating the MAPK-dependent immune responses in the Japanese
      flounder.

PMID- 28743633
TI  - An intra-neural microstimulation system for ultra-high field magnetic resonance
      imaging and magnetoencephalography.
AB  - BACKGROUND: Intra-neural microstimulation (INMS) is a technique that allows the
      precise delivery of low-current electrical pulses into human peripheral nerves.
      Single unit INMS can be used to stimulate individual afferent nerve fibres during
      microneurography. Combining this with neuroimaging allows the unique monitoring
      of central nervous system activation in response to unitary, controlled tactile
      input, with functional magnetic resonance imaging (fMRI) providing exquisite
      spatial localisation of brain activity and magnetoencephalography (MEG) high
      temporal resolution. NEW METHOD: INMS systems suitable for use within
      electrophysiology laboratories have been available for many years. We describe an
      INMS system specifically designed to provide compatibility with both ultra-high
      field (7T) fMRI and MEG. Numerous technical and safety issues are addressed. The
      system is fully analogue, allowing for arbitrary frequency and amplitude INMS
      stimulation. RESULTS: Unitary recordings obtained within both the MRI and MEG
      screened-room environments are comparable with those obtained in 'clean'
      electrophysiology recording environments. Single unit INMS (current <7MUA, 200MUs
      pulses) of individual mechanoreceptive afferents produces appropriate and robust
      responses during fMRI and MEG. COMPARISON WITH EXISTING METHOD(S): This custom
      built MRI- and MEG-compatible stimulator overcomes issues with existing INMS
      approaches; it allows well-controlled switching between recording and stimulus
      mode, prevents electrical shocks because of long cable lengths, permits unlimited
      patterns of stimulation, and provides a system with improved work-flow and
      participant comfort. CONCLUSIONS: We demonstrate that the requirements for an
      INMS-integrated system, which can be used with both fMRI and MEG imaging systems,
      have been fully met.

PMID- 28743634
TI  - Early ciliary and prominin-1 dysfunctions precede neurogenesis impairment in a
      mouse model of type 2 diabetes.
AB  - Diabetes mellitus (DM) is reaching epidemic conditions worldwide and increases
      the risk for cognition impairment and dementia. Here, we postulated that
      progenitors in adult neurogenic niches might be particularly vulnerable.
      Therefore, we evaluated the different components of the mouse subventricular zone
      (SVZ) during the first week after chemical induction of type 1 and type 2
      diabetes-like (T1DM and T2DM) conditions. Surprisingly, only T2DM mice showed SVZ
      damage. The initial lesions were localized to ependymal cilia, which appeared
      disorientated and clumped together. In addition, they showed delocalization of
      the ciliary membrane protein prominin-1. Impairment of neuroprogenitor
      proliferation, neurogenic marker abnormalities and ectopic migration of
      neuroblasts were found at a later stage. To our knowledge, our data describe for
      the first time such an early impact of T2DM on the SVZ. This is consistent with
      clinical data indicating that brain damage in T2DM patients differs from that in
      T1DM patients.

PMID- 28743635
TI  - Molecular imaging in drug development: Update and challenges for radiolabeled
      antibodies and nanotechnology.
AB  - Despite the significant advancement achieved in understanding the molecular
      mechanisms responsible for cancer transformation and aberrant proliferation,
      leading to novel targeted cancer therapies, significant effort is still needed to
      "personalize" cancer treatment. Molecular imaging is an emerging field that has
      shown the ability to characterize in vivo the molecular pathways present at the
      cancer cell level, enabling diagnosis and personalized treatment of malignancies.
      These technologies, particularly SPECT and PET also permit the development of
      novel radiotheranostic probes, which provide capabilities for diagnosis and
      treatment with the same agent. The small therapeutic index of most anticancer
      agents is a limitation in the drug development process. Incorporation of
      molecular imaging in clinical research may help in overcoming this limitation and
      favouring selection of patient populations most likely to achieve benefit from
      targeted therapy. This review will focus on two of the most advanced theranostic
      approaches with promising potential for application in the clinic: 1) therapeutic
      monoclonal antibodies which may be linked to a radionuclide for SPECT or PET
      imaging to guide cancer diagnosis, staging, molecular characterization, and
      assessment of the response to treatment and 2) multifunctional nanotechnology
      that allows image guided drug delivery through encapsulation of multiple
      therapeutic, targeting and imaging agents into a single nanoparticle. Porphysome,
      a liposome-like nanoparticle, is an example of a novel and promising application
      of nanotechnology for cancer diagnosis and treatment. These technologies have
      proven to be effective in preclinical models, warranting further clinical
      investigation to advance their application for the benefit of cancer patients.

PMID- 28743636
TI  - Valproate increases dopamine transporter expression through histone acetylation
      and enhanced promoter binding of Nurr1.
AB  - The dopamine transporter (DAT) is the key regulator of dopaminergic transmission
      and is a target of several xenobiotics, including pesticides and pharmacological
      agents. Previously, we identified a prominent role for histone deacetylases in
      the regulation of DAT expression. Here, we utilized a rat dopaminergic cell line
      (N27) to probe the responsiveness of DAT mRNA expression to inhibitors of histone
      acetylation. Inhibition of histone deacetylases (HDACs) by valproate, butyrate
      and Trichostatin A led to a 3-10-fold increase in DAT mRNA expression, a 50%
      increase in protein levels, which were accompanied by increased H3 acetylation
      levels. To confirm the mechanism of valproate-mediated increase in DAT mRNA,
      chromatin immunoprecipitation (ChIP) assays were used and demonstrated a
      significant increase in enrichment of acetylation of histone 3 on lysines 9 and
      14 (H3K9/K14ac) in the DAT promoter. Expression of Nurr1 and Pitx3, key
      regulators of DAT expression, were increased following valproate treatment and
      Nurr1 binding was enriched in the DAT promoter. Together, these results indicate
      that histone acetylation and subsequent enhancement of transcription factor
      binding are plausible mechanisms for DAT regulation by valproate and, perhaps, by
      other xenobiotics.

PMID- 28743637
TI  - Design considerations in coiled-coil fusion constructs for the structural
      determination of a problematic region of the human cardiac myosin rod.
AB  - X-ray structural determination of segments of the myosin rod has proved difficult
      because of the strong salt-dependent aggregation properties and repeating pattern
      of charges on the surface of the coiled-coil that lead to the formation of
      paracrystals. This problem has been resolved in part through the use of globular
      assembly domains that improve protein folding and prevent aggregation. The
      primary consideration now in designing coiled-coil fusion constructs for myosin
      is deciding where to truncate the coiled-coil and which amino acid residues to
      include from the folding domain. This is especially important for myosin that
      contains numerous regions of low predicted coiled-coil propensity. Here we
      describe the strategy adopted to determine the structure of the region that
      extends from Arg1677 - Leu1797 that included two areas that do not show a strong
      sequence signature of a conventional left-handed coiled coil or canonical heptad
      repeat. This demonstrates again that, with careful choice of fusion constructs,
      overlapping structures exhibit very similar conformations for the myosin rod
      fragments in the canonical regions. However, conformational variability is seen
      around Leu1706 which is a hot spot for cardiomyopathy mutations suggesting that
      this might be important for function.

PMID- 28743638
TI  - Efficient 3D-CTF correction for cryo-electron tomography using NovaCTF improves
      subtomogram averaging resolution to 3.4A.
AB  - Cryo-electron tomography (cryo-ET) allows cellular ultrastructures and
      macromolecular complexes to be imaged in three-dimensions in their native
      environments. Cryo-electron tomograms are reconstructed from projection images
      taken at defined tilt-angles. In order to recover high-resolution information
      from cryo-electron tomograms, it is necessary to measure and correct for the
      contrast transfer function (CTF) of the microscope. Most commonly, this is
      performed using protocols that approximate the sample as a two-dimensional (2D)
      plane. This approximation accounts for differences in defocus and therefore CTF
      across the tilted sample. It does not account for differences in defocus of
      objects at different heights within the sample; instead, a 3D approach is
      required. Currently available approaches for 3D-CTF correction are
      computationally expensive and have not been widely implemented. Here we simulate
      the benefits of 3D-CTF correction for high-resolution subtomogram averaging, and
      present a user-friendly, computationally-efficient 3D-CTF correction tool,
      NovaCTF, that is compatible with standard tomogram reconstruction workflows in
      IMOD. We validate the approach on synthetic data and test it using subtomogram
      averaging of real data. Consistent with our simulations, we find that 3D-CTF
      correction allows high-resolution structures to be obtained with much smaller
      subtomogram averaging datasets than are required using 2D-CTF. We also show that
      using equivalent dataset sizes, 3D-CTF correction can be used to obtain higher
      resolution structures. We present a 3.4A resolution structure determined by
      subtomogram averaging.

PMID- 28743639
TI  - Bidirectional mechanobiology between cells and their local extracellular matrix
      probed by atomic force microscopy.
AB  - There is growing recognition that the mechanical interactions between cells and
      their local extracellular matrix (ECM) are central regulators of tissue
      development, homeostasis, repair and disease progression. The unique ability of
      atomic force microscopy (AFM) to probe quantitatively mechanical properties and
      forces at the nanometer or micrometer scales in all kinds of biological samples
      has been instrumental in the recent advances in cell and tissue mechanics. In
      this review we illustrate how AFM has provided important insights on our current
      understanding of the mechanobiology of cells, ECM and cell-ECM bidirectional
      interactions, particularly in the context of soft acinar tissues like the mammary
      gland or pulmonary tissue. AFM measurements have revealed that intrinsic cell
      micromechanics is cell-type specific, and have underscored the prominent role of
      beta1 integrin/FAK(Y397) signaling and the actomyosin cytoskeleton in the
      mechanoresponses of both parenchymal and stromal cells. Moreover AFM has unveiled
      that the micromechanics of the ECM obtained by tissue decellularization is unique
      for each anatomical compartment, which may support both its specific function and
      cell differentiation. AFM has also enabled identifying critical mechanoregulatory
      proteins involved in branching morphogenesis (MMP14) and acinar differentiation
      (alpha3beta1 integrin), and has clarified the role of altered tissue mechanics
      and architecture in a variety of pathologic conditions. Critical technical issues
      of AFM mechanical measurements like tip geometry effects are also discussed.

PMID- 28743640
TI  - Structural origins of clustered protocadherin-mediated neuronal barcoding.
AB  - Clustered protocadherins mediate neuronal self-recognition and non-self
      discrimination-neuronal "barcoding"-which underpin neuronal self-avoidance in
      vertebrate neurons. Recent structural, biophysical, computational, and cell-based
      studies on protocadherin structure and function have led to a compelling
      molecular model for the barcoding mechanism. Protocadherin isoforms assemble into
      promiscuous cis-dimeric recognition units and mediate cell-cell recognition
      through homophilic trans-interactions. Each recognition unit is composed of two
      arms extending from the membrane proximal EC6 domains. A cis-dimeric recognition
      unit with each arm coding adhesive trans homophilic specificity can generate a
      zipper-like assembly that in turn suggests a chain termination mechanism for self
      vs-non-self-discrimination among vertebrate neurons.

PMID- 28743642
TI  - Intercontinental and intracontinental biogeography of the eastern Asian - Eastern
      North American disjunct Panax (the ginseng genus, Araliaceae), emphasizing its
      diversification processes in eastern Asia.
AB  - The intercontinental biogeography between eastern Asia and eastern North America
      has attracted much attention from evolutionary biologists. Further insights into
      understanding the evolution of the intercontinental disjunctions have been
      hampered by the lack of studies on the intracontinental biogeography in eastern
      Asia, a region with complex geology, geography, climates and habitats. Herein we
      studied the biogeographic history of the eastern Asian-eastern North American
      disjunct genus Panax with special emphasis on the investigation of its uneven
      diversification in Asia. This study reconstructs the diversification history of
      Panax and also emphasizes a large clade of Panax taxa, which has a wide
      distribution in eastern Asia, but was unresolved in previous studies. We examined
      the noncoding plastid DNA fragments of trnH-psbA, rps16, and psbM-trnD, the
      mitochondrial b/c intron of NAD1, and the nuclear ribosomal internal transcribed
      spacer (ITS) region of 356 samples from 47 populations. The results revealed the
      subtropical Northern Hemisphere origin (Asia or Asia and North America) of Panax
      in the Paleocene. Intercontinental disjunctions between eastern Asia and eastern
      North America formed twice in Panax, once estimated in early Eocene for the split
      of P. trifolius and another in mid-Miocene for the divergence of P.
      quinquefolius. Intercontinental diversifications in Panax showed temporal
      correlation with the increase of global temperature. The evolutionary radiation
      of the P. bipinnatifidus species complex occurred around the boundary of
      Oligocene and Miocene. Strong genetic structure among populations of the species
      complex was detected and the populations may be isolated by distance. The
      backbone network and the Bayesian clustering analysis revealed a major
      evolutionary radiation centered in the Hengduan Mountains of western China. Our
      results suggested that the evolutionary radiation of Panax was promoted by
      geographic barriers, including mountain ranges (Hengduan Mountains, Nanling
      Mountains and Wuyishan Mountains), oceans and altitudinal shifts, which further
      contribute to the knowledge of the uneven species diversification between eastern
      Asia and North America.

PMID- 28743641
TI  - Respiratory chain supercomplexes: Structures, function and biogenesis.
AB  - Over the past sixty years, researchers have made outmost efforts to clarify the
      structural organization and functional regulation of the complexes that configure
      the mitochondrial respiratory chain. As a result, the entire composition of each
      individual complex is practically known and, aided by notable structural advances
      in mammals, it is now widely accepted that these complexes stablish interactions
      to form higher-order supramolecular structures called supercomplexes and
      respirasomes. The mechanistic models and players that regulate the function and
      biogenesis of such superstructures are still under intense debate, and represent
      one of the hottest topics of the mitochondrial research field at present.
      Noteworthy, understanding the pathways involved in the assembly and organization
      of respiratory chain complexes and supercomplexes is of high biomedical relevance
      because molecular alterations in these pathways frequently result in severe
      mitochondrial disorders. The purpose of this review is to update the structural,
      biogenetic and functional knowledge about the respiratory chain supercomplexes
      and assembly factors involved in their formation, with special emphasis on their
      implications in mitochondrial disease. Thanks to the integrated data resulting
      from recent structural, biochemical and genetic approaches in diverse biological
      systems, the regulation of the respiratory chain function arises at multiple
      levels of complexity.

PMID- 28743643
TI  - Molecular data reveal a tropical freshwater origin of Naidinae (Annelida,
      Clitellata, Naididae).
AB  - The phylogenetic relationships within Naidinae (Annelida, Clitellata, Naididae)
      were investigated, using six molecular markers, both mitochondrial (12S rDNA, 16S
      rDNA, the COI gene) and nuclear (18S rDNA, 28S rDNA, the ITS region). Thirty
      seven nominal species, representing 16 of the 22 genera recognized in the
      subfamily, were included, and the Nais communis/variabilis species complex was
      represented by six different morphotypes. Ten other species of Naididae were
      selected as outgroups. The data were analysed by Bayesian inference and Maximum
      Likelihood. The phylogeny corroborates monophyly of the Naidinae, and the
      separate status of the genus Pristina (Pristininae) and the Opistocystinae.
      Relationships within Naidinae are largely well supported, but in some parts
      unexpected: (1) A clade containing the largely tropical genera Dero and
      Branchiodrilus is sister to the rest of the subfamily, and together with a third
      tropical genus, Allonais, they form a basal paraphyly. All these genera show
      morphological adaptations to environmental hypoxia, leading to the conclusion
      that Naidinae originated in tropical freshwaters. (2) The genera Dero, Nais and
      Piguetiella are paraphyletic. (3) At least Branchiodrilus, Paranais,
      Chaetogaster, Nais, Stylaria appear to contain cryptic species. Morphological
      characters, especially those associated with chaetae, are to a great extent
      homoplastic within Naidinae, which certainly has contributed to the overall
      taxonomic confusion of this subfamily.

PMID- 28743644
TI  - Species trees from consensus single nucleotide polymorphism (SNP) data: Testing
      phylogenetic approaches with simulated and empirical data.
AB  - Datasets of hundreds or thousands of SNPs (Single Nucleotide Polymorphisms) from
      multiple individuals per species are increasingly used to study population
      structure, species delimitation and shallow phylogenetics. The principal software
      tool to infer species or population trees from SNP data is currently the BEAST
      template SNAPP which uses a Bayesian coalescent analysis. However, it is
      computationally extremely demanding and tolerates only small amounts of missing
      data. We used simulated and empirical SNPs from plants (Australian Craspedia,
      Asteraceae, and Pelargonium, Geraniaceae) to compare species trees produced (1)
      by SNAPP, (2) using SVD quartets, and (3) using Bayesian and parsimony analysis
      with several different approaches to summarising data from multiple samples into
      one set of traits per species. Our aims were to explore the impact of tree
      topology and missing data on the results, and to test which data summarising and
      analyses approaches would best approximate the results obtained from SNAPP for
      empirical data. SVD quartets retrieved the correct topology from simulated data,
      as did SNAPP except in the case of a very unbalanced phylogeny. Both methods
      failed to retrieve the correct topology when large amounts of data were missing.
      Bayesian analysis of species level summary data scoring the two alleles of each
      SNP as independent characters and parsimony analysis of data scoring each SNP as
      one character produced trees with branch length distributions closest to the true
      trees on which SNPs were simulated. For empirical data, Bayesian inference and
      Dollo parsimony analysis of data scored allele-wise produced phylogenies most
      congruent with the results of SNAPP. In the case of study groups divergent enough
      for missing data to be phylogenetically informative (because of additional
      mutations preventing amplification of genomic fragments or bioinformatic
      establishment of homology), scoring of SNP data as a presence/absence matrix
      irrespective of allele content might be an additional option. As this depends on
      sampling across species being reasonably even and a random distribution of non
      informative instances of missing data, however, further exploration of this
      approach is needed. Properly chosen data summary approaches to inferring species
      trees from SNP data may represent a potential alternative to currently available
      individual-level coalescent analyses especially for quick data exploration and
      when dealing with computationally demanding or patchy datasets.

PMID- 28743645
TI  - Extensively drug-resistant tuberculosis (XDR-TB) in Morocco.
AB  - OBJECTIVES: Extensively drug-resistant tuberculosis (XDR-TB) has recently been
      identified as a major global health threat. The aim of this study was to evaluate
      the presence of XDR-TB among Mycobacterium tuberculosis isolates in Morocco and
      its association with demographic, clinical and epidemiological features. METHODS:
      A total of 524 patients from the Moroccan National Tuberculosis Reference
      Laboratory, representative of all of the geographic regions, were subject to
      first-line drug susceptibility testing (DST). Subsequently, 155 isolates found to
      be multidrug-resistant tuberculosis (MDR-TB) underwent second-line DST. Moreover,
      to enhance our understanding of the genetic basis of these drug-resistant
      strains, drug resistance-associated mutations were investigated in isolates
      either identified as pre-XDR- and XDR-TB or suspected resistant using the
      GenoType(r) MTBDRsl V1.0 assay. RESULTS: In this study, 4 (2.6%) XDR-TB and 18
      (11.6%) pre-XDR-TB isolates were identified. Agreement between the MTBDRsl assay
      results and phenotypic DST was 95.2% for ofloxacin, 81.0% for kanamycin and 95.2%
      for amikacin. CONCLUSIONS: To the best of our knowledge, this is the first study
      to evaluate the frequency of XDR-TB in Morocco. These results highlight the need
      to reinforce the TB management policy in Morocco with regard to control and
      detection strategies in order to prevent further spread of XDR-TB isolates.

PMID- 28743646
TI  - Sepsis and septic shock: New definitions, new diagnostic and therapeutic
      approaches.
AB  - Sepsis and septic shock are common life-threatening pathologies associated with
      high mortality and substantial costs for healthcare system. Clinical guidelines
      and bundles for the management of patients with sepsis have recently been
      updated. Herein, we review the history of sepsis and related conditions
      definitions from the first consensus conference in 1991 to nowadays, the
      epidemiologic data resulting from worldwide studies on incidence and mortality,
      the diagnostic approaches including the microbiological assessment of infection
      and the use of several prognostic and diagnostic biomarkers and finally we review
      the main therapeutic measures as the intravenous immunoglobulin therapy and the
      administration of appropriate antibiotic treatment to provide patients with
      sepsis a favourable outcome in the antibiotic-resistance era.

PMID- 28743647
TI  - Prevalence and characterisation of quinolone resistance genes in Aeromonas spp.
      isolated from pet turtles in South Korea.
AB  - OBJECTIVES: The aim of this study was to characterise Aeromonas spp. isolated
      from popular species of pet turtle to assess the potential risk of pet turtles as
      a source of target gene alterations in the quinolone resistance-determining
      region (QRDR) and transferable plasmid-mediated quinolone resistance (PMQR)
      genes. METHODS: Twenty-five isolates comprising four species, namely Aeromonas
      enteropelogenes, Aeromonas hydrophila, Aeromonas caviae and Aeromonas veronii,
      were obtained from healthy pet turtles. The antimicrobial susceptibility of the
      isolates to nalidixic acid, ciprofloxacin and ofloxacin was examined by minimum
      inhibitory concentration (MIC) determination. QRDR substitutions and PMQR genes
      were detected using conventional PCR assays and sequencing. RESULTS: Although
      more than one-half of the isolates were resistant to nalidixic acid (14/25; 56%),
      most were susceptible to ciprofloxacin and ofloxacin. In QRDR substitution
      analysis, gyrA Ser-83->Ile substitution was predominant among A. enteropelogenes
      isolates, whilst two isolates of A. caviae displayed a novel Asp-95->Pro
      substitution. With regard to parC, Ser-80->Ile substitution was noted in all
      species except A. veronii. Furthermore, qnrS, qnrB and aac(6')-Ib-cr genes were
      detected in 68% (17/25), 8% (2/25) and 8% (2/25) of the isolates, respectively;
      86% (12/14) of A. enteropelogenes isolates harboured a qnrS gene. Unexpectedly,
      quinolone resistance determinants were also detected in some isolates that were
      phenotypically susceptible to the tested quinolones. CONCLUSIONS: The current
      study reveals the mismatch phenomenon between quinolone resistance phenotype and
      genotype of turtle-borne aeromonads and suggests that susceptible isolates might
      be a potential risk source for storage and transmission of resistance genes.

PMID- 28743648
TI  - Drug resistance and Mycobacterium tuberculosis strain diversity in TB/HIV co
      infected patients in Ho Chi Minh city, Vietnam.
AB  - BACKGROUND: Mycobacterium tuberculosis strain diversity and drug resistance among
      people living with human immunodeficiency virus (HIV) in Vietnam have not been
      described previously. METHODS: We examined M. tuberculosis isolates from TB/HIV
      co-infected patients in Ho Chi Minh City, Vietnam. Drug susceptibility testing
      (DST), spoligotyping and 24-locus Mycobacterial Interspersed Repetitive Unit
      (MIRU-24 typing) were performed, and the rpoB, katG, inhA and inhA promoter,
      rpsL, rrs and embB genes were sequenced in all drug resistant isolates
      identified. RESULTS: In total, 84/200 (42.0%) strains demonstrated "any drug
      resistance"; 17 (8.5%) were multi-drug resistant (MDR). Streptomycin resistance
      was present in 80 (40.0%) isolates; 95.2% (80/84) with "any drug resistance" and
      100% with MDR. No rifampicin monoresistance was detected. Of the rifampicin
      resistant strains 16/18 (88.9%) had mutations in the 81-bp Rifampicin Resistance
      Defining Region (RRDR) of the rpoB gene. Isoniazid resistance was mostly
      associated with Ser315Thr mutations in the katG gene (15/17; 88.2%). Beijing
      (49.0%) and East African Indian (EAI) lineage strains (35.0%; 56/70 EAI-5) were
      most common. CONCLUSION: TB/HIV co-infection in Vietnam was associated with high
      rates of TB drug resistance, although we were unable to differentiate new from
      retreatment cases.

PMID- 28743649
TI  - First report of blaOXA-181-mediated carbapenem resistance in Aeromonas caviae in
      association with pKP3-A: Threat for rapid dissemination.
AB  - OBJECTIVES: Carbapenemase-producing Aeromonas spp. are of great concern in
      healthcare settings and are also known to acquire clinically relevant resistance
      genes. In this study, carbapenem-non-susceptible Aeromonas isolates were
      characterised for their molecular mechanisms of resistance. METHODS: Among 180
      Aeromonas isolates, 10 carbapenem-non-susceptible isolates were selected based on
      their antimicrobial susceptibility profile. Carbapenemase production was
      investigated by the CarbaNP test. ESBL-, AmpC- and carbapenemase-encoding genes
      were screened by PCR. Isolates VBF557 and VBF856 with high MICs for imipenem were
      selected for whole-genome sequencing (WGS). Conjugation experiments were
      performed to determine the transmissibility of resistance. RESULTS: WGS
      remarkably revealed the presence of class D beta-lactamases (AmpS/AmpH), class C
      beta-lactamases and class B2 metallo-beta-lactamase (cphA3) in VBF557. In
      contrast, VBF856 had multiple resistance genes coding for aminoglycoside,
      sulphonamide, carbapenem (blaOXA-181 class D beta-lactamase), macrolide,
      fluoroquinolone, rifampicin, phenicol, tetracycline and trimethoprim resistance.
      This is the first global report of blaOXA-181 in Aeromonas spp. Interestingly,
      blaOXA-181 was identified in association with transposon Tn2013 in plasmid pKP3
      A. Additionally, an IncQ2 plasmid with qnrS2 was identified. Among the tested
      isolates, VBF1116 and VBF888 possessed blaNDM and blaVEB, respectively, by PCR.
      None of the other isolates harboured any tested beta-lactamase genes. The
      resistance gene was transmissible in the presence of imipenem. CONCLUSIONS:
      Presence of such resistance genes in plasmids further adds complexity for control
      of spread of carbapenem resistance. This study reveals the emergence of
      carbapenem resistance among Aeromonas spp. and the importance of mobile genetic
      elements such as plasmids in interchanging resistance determinants between
      species.

PMID- 28743650
TI  - Analysis of interactions of clinical mutants of catalase-peroxidase (KatG)
      responsible for isoniazid resistance in Mycobacterium tuberculosis with
      derivatives of isoniazid.
AB  - OBJECTIVES: Isoniazid (INH) resistance is a major contributor to the emergence of
      multidrug resistance in Mycobacterium tuberculosis (MTB), hampering the success
      of tuberculosis treatment. This study aimed to identify good leads based on INH
      derivatives against INH-resistant MTB strains. Mutations at codon 315 in the katG
      gene encoding catalase-peroxidase (KatG) are the major cause of INH resistance in
      MTB. The most prevalent substitution is S315T; other substitutions include S315I,
      S315R, S315N and S315G. METHODS: In this study, all five naturally occurring
      mutants (S315T, S315I, S315R, S315N and S315G) of KatG were docked and simulated
      with 50 INH derivatives in comparison with the wild-type (WT) KatG. RESULTS: The
      docking results suggested that compounds C30, C45 and C50 gave the highest scores
      when bound to the mutants of KatG. Of note, C50 produced a high score with the WT
      as well as with three mutants (S315T, S315I and S315R). Simulation studies
      indicated that C50 exhibited minimal deviation and fluctuation between WT and
      three mutants compared with C30 and C45, which displayed significant changes with
      WT and the S315N and S315G mutants, respectively. CONCLUSIONS: C50 can be
      considered as a better lead for INH-resistant strains. These models demonstrate
      the binding interaction of all naturally occurring KatG mutants of MTB at
      position 315 with derivatives of INH. This information will be helpful for lead
      compound-based identification of derivatives that may be used against INH
      resistant MTB strains and may provide a useful structural framework for designing
      new antitubercular agents that can circumvent INH resistance.

PMID- 28743651
TI  - Resistance to quinolones, cephalosporins and macrolides in Escherichia coli
      causing bacteraemia in Peruvian children.
AB  - OBJECTIVES: To characterise the beta-lactam, quinolone and macrolide resistance
      levels and mechanisms in 62 Escherichia coli isolates causing bacteraemia in
      Peruvian children. METHODS: Minimum inhibitory concentrations (MICs) of
      ciprofloxacin, nalidixic acid (NAL) and azithromycin were determined in the
      presence and absence of Phe-Arg-beta-naphthylamide. Susceptibility to other 14
      antimicrobial agents was also established. Extended-spectrum beta-lactamases
      (ESBLs) were identified, and mutations in gyrA and parC as well as the presence
      of transferable mechanisms of quinolone resistance (TMQR) and macrolide
      resistance (TMMR) were determined. RESULTS: Fifty isolates (80.6%) were multidrug
      resistant. High proportions of resistance to ampicillin (93.5%), NAL (66.1%) and
      trimethoprim/sulfamethoxazole (66.1%) were observed. No isolate showed resistance
      to carbapenems and only two isolates were resistant to nitrofurantoin. Twenty
      seven isolates carried ESBL-encoding genes: 2 blaSHV-12; 13 blaCTX-M-15; 4 blaCTX
      M-2; 6 blaCTX-M-65; and 2 non-identified ESBLs. Additionally, 27 blaTEM-1 and 9
      blaOXA-1-like genes were detected. All quinolone-resistant isolates showed target
      mutations, whilst TMQR were present in four isolates. Efflux pumps played a role
      in constitutive NAL resistance. The association between quinolone resistance and
      ESBL production was significant (P=0.0011). The mph(A) gene was the most frequent
      TMMR (16 isolates); msr(A) and erm(B) genes were also detected. Only one TMMR
      carrying isolate [presenting mph(A) and erm(B) concomitantly] remained resistant
      to azithromycin when efflux pumps were inhibited. CONCLUSIONS: A variety of ESBL
      encoding genes and widespread of blaCTX-M-15 in Lima has been shown. The role of
      efflux pumps in azithromycin resistance needs to be further evaluated, as well as
      effective control of the use of antimicrobial agents.

PMID- 28743652
TI  - Molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae at a Turkish
      centre: Is the increase of resistance a threat for Europe?
AB  - OBJECTIVES: In recent years, carbapenem-resistant Klebsiella pneumoniae (CRKP)
      have become an important threat to hospitalised patients. This study aimed to
      identify the genetic mechanisms of carbapenem resistance in CRKP isolated from
      patients in a Turkish centre. METHODS: During 2013-2014, a total of 98 K.
      pneumoniae isolated from patients at Cukurova University Balcali Hospital (Adana,
      Turkey) determined phenotypically as resistant to carbapenems were screened
      genotypically for the presence of carbapenemase enzymes by multiplex PCR.
      RESULTS: Of the 98 patients for whom genetic investigation was made, 93 (94.9%)
      were adults, 56 (57.1%) were male and 81 (82.7%) were diagnosed as infected. The
      mean and median age were 51.8+/-20.5years and 55 years (range 1-89 years),
      respectively. The nosocomial infection rate was 87.8% (86/98). The mortality rate
      was 41.8% (41/98). Fifty-eight patients (59.2%) were admitted to intensive care
      units. Of the 12 non-nosocomial infections, 5 (41.7%) originated from the
      inpatient clinic of the urology department. The mean and median hospital length
      of stay (LOS) were 20.7+/-20.8days and 17days (range 0-90 days), respectively.
      The most common carbapenemase gene detected was blaOXA-48 (74.5%), followed by
      blaVIM (45.9%) and blaSME (37.8%). The blaNDM gene was detected in 20 isolates
      (20.4%). The most effective antibiotics were tigecycline and colistin, with
      susceptibility rates of 87.5% and 74.3%, respectively. CONCLUSIONS: Multiple
      resistance mechanisms were present in CRKP isolates in Turkey. Most of the
      isolates harboured blaOXA-48, blaVIM and blaSME genes; meanwhile, the rate of
      20.4% for blaNDM is alarming.

PMID- 28743653
TI  - A Review of Arteriovenous Fistulae Creation in Octogenarians.
AB  - BACKGROUND: To analyze the outcomes of arteriovenous fistulae (AVFs) creation in
      octogenarians. METHODS: A retrospective study of 47 AVFs created in patients aged
      80 years and above from 2008 to 2014. Patient and AVF characteristics and
      outcomes were evaluated. Predictors of patency were analyzed with multivariate
      analysis and Kaplan-Meier patency, and survival analysis was performed. RESULTS:
      Forty-seven of 1,259 AVFs created were for octogenarians (4%). Mean age was 83
      years old (range: 80-91 years), with 27 male (57%) and 35 with tunneled dialysis
      catheters in situ (75%). There were a total of 15 (32%) radiocephalic AVFs, 30
      (64%) brachial-cephalic AVFs, and 2 (4%) brachial-basilic transposition AVFs. At
      12 months, assisted primary patency rate was 28% (13 patients) while primary
      failure rate was 72% (34 patients). Subset analysis showed brachial-cephalic AVFs
      to have the highest assisted primary patency rate at 33%. Within 24 months,
      tunneled dialysis catheter-related sepsis rate was 31% (11 patients).
      Multivariate analysis did not reveal any factor to be statistically significant
      in predicting AVF patency. Kaplan-Meier survival curve showed a 50% survival rate
      at 63 months after AVF creation. CONCLUSIONS: In view of high AVF primary failure
      rate and relatively low tunneled dialysis catheter bacteremia rate, long-term
      tunneled dialysis catheters as the main form of hemodialysis renal access may be
      a viable option. However, with 50% of end-stage renal failure patients surviving
      up to 63 months after AVF creation, the risks and benefits of long-term tunneled
      dialysis catheters must be balanced against those of AVF creation.

PMID- 28743654
TI  - Endografting under Assistance of Transapical Body Floss Through-and-Through
      Wiring Technique and Rapid Ventricular Pacing for an Ascending Aortic Tuberculous
      Pseudoaneurysm.
AB  - BACKGROUND: To demonstrate an ascending aortic tuberculosis pseudoaneurysm
      successfully treated with endografts under assistance of trans-apical body floss
      wiring technique and rapid ventricular pacing support. METHOD AND RESULT: A 77
      year-old woman with a non-healing anteromedial chest wound presented with sudden
      hypotension and hemoptysis. The computed tomography (CT) scan revealed a 9-cm
      diameter pseudoaneurysm of ascending aorta, with sternal erosion close to the
      wound. Conventional open repair was not preferred due to possible contamination
      of interposition graft and difficult sternum closure. The feasibility of
      endografting was confirmed based on appropriate landing zones. After endografts
      modification at back table, we made a left mini-thoracotomy and establish a
      through-and-through body floss wire from left ventricular apex to femoral artery.
      Retrograde delivery over this wire from femoral artery to ascending aorta and
      deployment of endografts under rapid ventricular pacing support were performed
      smoothly. Final angiography showed no endoleaks with patent coronary and arch
      vessels. Further wound debridement was done at the same time and wound culture
      yielded tuberculosis. After completing anti-tuberculosis therapy, no recurrent
      infection occurred. Postoperative 6-month CT scan disclosed optimal result.
      CONCLUSION: With adequate landing zones and delicate surgical strategy,
      endografting with anti-tuberculosis therapy may be an alternative treatment for
      ascending aortic tuberculosis pseudoaneurysm.

PMID- 28743655
TI  - Negative chemotaxis of Ralstonia pseudosolanacearum to maleate and identification
      of the maleate chemosensory protein.
AB  - Ralstonia pseudosolanacearum Ps29 was repelled by maleate. Screening of a
      complete collection of Ps29 single-methyl-accepting chemotaxis protein (mcp) gene
      mutants identified the RSp0303 homolog (McpP) as a chemotaxis sensor mediating
      negative chemotaxis to maleate. Interestingly, the mcpP-deletion mutant was
      attracted to maleate, indicating that this bacterium expresses a MCP(s) for both
      positive and negative chemotaxis to maleate. We constructed a Ps29 derivative
      (designated POC14) harboring deletions in 14 individual mcp genes, including
      mcpP, to characterize McpP. Introduction of a plasmid harboring the mcpP gene
      (pPS16) restored the ability to negatively respond to maleate, confirming that
      McpP is a MCP for negative chemotaxis to maleate. We thought that maleate might
      be applied to controlling plant infection by R. pseudosolanacearum. To evaluate
      this possibility, we measured chemotactic responses of seven other virulent R.
      pseudosolanacearum strains to maleate. We confirmed that they harbored functional
      mcpP orthologues, but they showed no chemotactic responses to maleate.
      Quantitative RT-PCR analysis revealed that these seven R. pseudosolanacearum
      strains did not show negative chemotaxis to maleate because of negligible
      transcription of the mcpP genes. We compared the chemotactic responses of POC14
      and POC14[pPS16] toward various chemicals and found that McpP senses inorganic
      phosphate as a chemoattractant.

PMID- 28743656
TI  - Development of a rapid immunoassay system: Luminescent detection of antigen
      associated antibody-luciferase in the presence of a dye that absorbs light from
      free antibody-luciferase.
AB  - In this report, we developed a rapid immunoassay system, designated the
      bioluminescent interference gathering optical (BINGO) assay, which required no
      time-consuming washing steps for removal of unbound antibodies. This system
      employed a luciferase (Luc)-conjugated antibody (LucAb) and a dye that absorbed
      light from the LucAb. The antigen-associated LucAb was localized by transfer of
      an antigen to the detector-side of a chamber where a detector photomultiplier
      tube (PMT) was installed. In contrast, the free LucAb was distributed throughout
      the solution, and the light emitted by the free LucAb was absorbed by the dye.
      Therefore, only light from LucAb associated with antigen could be detected by the
      PMT. The new system could be used to rapidly detect the amount of antigen
      antibody-Luc complex by collecting steps, such as centrifugation or magnetic
      collection of antibody-coated magnetic beads. Proof-of-principle experiments were
      performed using a model system with streptavidin beads and biotinylated Luc. The
      feasibility of the system was demonstrated using magnetic beads coated with anti
      Escherichia coli O157 antibody, enabling detection of 4 * 103 cells in only 15
      min. Thus, this system may have applications in a variety of biomedical fields.

PMID- 28743657
TI  - Vinegar production from post-distillation slurry deriving from rice shochu
      production with the addition of caproic acid-producing bacteria consortium and
      lactic acid bacterium.
AB  - To establish a zero emission process, the post-distillation slurry of a new type
      of rice shochu (NTRS) was used for the production of health promoting vinegar.
      Since the NTRS post-distillation slurry contained caproic acid and lactic acid,
      the effect of these two organic acids on acetic acid fermentation was first
      evaluated. Based on these results, Acetobacter aceti CICC 21684 was selected as a
      suitable strain for subsequent production of vinegar. At the laboratory scale,
      acetic acid fermentation of the NTRS post-distillation slurry in batch mode
      resulted in an acetic acid concentration of 41.9 g/L, with an initial ethanol
      concentration of 40 g/L, and the acetic acid concentration was improved to 44.5
      g/L in fed-batch mode. Compared to the NTRS post-distillation slurry, the vinegar
      product had higher concentrations of free amino acids and inhibition of
      angiotensin I converting enzyme activity. By controlling the volumetric oxygen
      transfer coefficient to be similar to that of the laboratory scale production, 45
      g/L of acetic acid was obtained at the pilot scale, using a 75-L fermentor with a
      working volume of 40 L, indicating that vinegar production can be successfully
      scaled up.

PMID- 28743658
TI  - High-level expression and characterization of solvent-tolerant lipase.
AB  - In this study, the coding sequence of the lipase from Proteus sp. SW1 was
      optimized via codon optimization and subjected to expression in Pichia pastoris
      GS115. The maximum enzyme yield was 387 mg/L in the supernatants of the shake
      flask culture. The purified recombinant lipase exhibited a specific activity of
      130 U/mg toward p-nitrophenyl Laurate. Its optimum pH and temperature were 8.0
      and 40 degrees C, respectively. It was highly stable and even activated in water
      miscible solvents, showing over 102% residual activity after 24 h incubation in
      ethanol, acetone, isopropanol and acetonitrile. In addition, the enzyme showed
      promoted activity with the increasing concentrations of methanol/ethanol and
      exhibited the maximum activity at 80%. In a solvent-free system for biodiesel
      synthesis with a one-step addition of methanol, the recombinant lipase displayed
      a 87% conversion rate toward palm oil at the high water content of 80%. The
      highly improved expression level and activity of the recombinant lipase may
      contribute to enable its commercial-scale production, and the unique properties
      would make it a particularly promising biocatalyst for biodiesel production in
      the future.

PMID- 28743659
TI  - A Randomized Clinical Trial of Caregiver-Delivered Reflexology for Symptom
      Management During Breast Cancer Treatment.
AB  - PURPOSE: The objective of this study was to determine the effects of a home-based
      reflexology intervention delivered by a friend/family caregiver compared with
      attention control on health-related quality of life of women with advanced breast
      cancer undergoing chemotherapy, targeted and/or hormonal therapy. METHODS:
      Patient-caregiver dyads (N = 256) were randomized to four weekly reflexology
      sessions or attention control. Caregivers in the intervention group were trained
      in a 30-minute protocol. During the four weeks, both groups had telephone symptom
      assessments, and intervention group had fidelity assessments. The intervention
      effects were assessed using linear mixed-effects models at weeks 5 and 11 for
      symptom severity and interference with daily activities, functioning, social
      support, quality of patient-caregiver relationship, and satisfaction with life.
      RESULTS: Significant reductions in average symptom severity (P = 0.02) and
      interference (P < 0.01) over 11 weeks were found in the reflexology group
      compared with control, with no group differences in functioning, social support,
      quality of relationship, or satisfaction with life at weeks 5 and 11. Stronger
      quality of relationship was associated with lower symptom interference in the
      entire sample (P = 0.02), but controlling for it did not diminish the effect of
      intervention on symptoms. Significant reductions in symptom severity in the
      reflexology group compared with attention control were seen during weeks 2-5 but
      were reduced at Week 11. DISCUSSION: Efficacy findings of caregiver-delivered
      reflexology with respect to symptom reduction open a new evidence-based avenue
      for home-based symptom management.

PMID- 28743661
TI  - Chronic Pain, Patient-Physician Engagement, and Family Communication Associated
      With Drug-Using HIV Patients' Discussing Advanced Care Planning With Their
      Physicians.
AB  - CONTEXT: In the era of effective antiretroviral therapy, persons living with
      HIV/AIDS (PLWHA) are living longer, transforming HIV into a serious chronic
      illness, warranting patient-provider discussion about advanced care planning
      (ACP). Evidence is needed to inform physicians on how to approach ACP for these
      patients. Chronic pain is common in PLWHA, particularly in those who have
      substance use disorders; although it is known that this population is at risk for
      poorer patient-physician engagement, the effects on ACP are unknown. OBJECTIVES:
      To further characterize factors associated with successful ACP in PLWHA, we
      examined associations between patient-physician relationship, chronic pain,
      family communication and problem-solving skills, and rates of patients discussing
      ACP with their physicians. METHODS: Data were from the Affirm Care study (N =
      325), which examined social and environmental factors associated with health
      outcomes among PLWHA and their informal caregivers. RESULTS: In multivariate
      analysis, higher odds of patient reports of discussing ACP with their physicians
      were associated with their higher rating of their relationship with their
      physician (adjusted odds ratio [AOR] 1.73; P < 0.05), higher levels of chronic
      pain (AOR 2.16; P < 0.05), experiencing prior family arguments about end-of-life
      medical decisions (AOR 2.43; P < 0.01), and feeling comfortable talking to family
      members about problems (AOR 1.33; P < 0.05). CONCLUSION: These results suggest
      that interventions to increase ACP among HIV patients and their physicians should
      promote patient-centered patient-provider relationships and PLWHAs' family
      communication and family problem-solving skills. The findings also suggest that
      PLWHA with chronic pain and prior family discord over end-of-life medical
      decisions may be primed for ACP.

PMID- 28743660
TI  - Oxaliplatin-Induced Peripheral Neuropathy and Identification of Unique Severity
      Groups in Colorectal Cancer.
AB  - CONTEXT: Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose-limiting
      toxicity of oxaliplatin and affects most colorectal cancer patients. OIPN is
      commonly evaluated by patient symptom report, using scales to reflect impairment.
      They do not discriminate between unique grouping of symptoms and signs, which
      impedes prompt identification of OIPN. OBJECTIVE: The objective of this study was
      to identify clusters of symptoms and signs that differentiated underlying
      clinical severity and segregated patients within our population into OIPN
      subgroups. METHODS: Chemotherapy-naive colorectal cancer patients (N = 148)
      receiving oxaliplatin were administered the Total Neuropathy Score clinical
      (TNSc(c)), which includes symptom report (sensory, motor, autonomic) and sensory
      examination (pin sense, vibration, reflexes). The TNSc was administered before
      chemotherapy initiation (T0) and after cumulative doses of oxaliplatin 510-520
      mg/m2 (T1) and 1020-1040 mg/m2 of oxaliplatin (T2). Using mean T2 TNSc scores,
      latent class analysis grouped patients into OIPN severity cohorts. RESULTS:
      Latent class analysis categorized patients into four distinct OIPN groups: low
      symptoms and low signs (n = 54); low symptoms and intermediate signs (n = 44);
      low symptoms and high signs (n = 21); and high symptoms and high signs (n = 29).
      No differences were noted among OIPN groups on age, sex, chemotherapy regimen, or
      cumulative oxaliplatin dose. CONCLUSION: We identified OIPN patient groups with
      distinct symptoms/signs, demonstrating variability of OIPN presentation
      regardless of cumulative oxaliplatin dose. Over half of the sample had positive
      findings on OIPN examination despite little or no symptoms. Sensory examination
      of all patients receiving oxaliplatin is indicated for timely identification of
      OIPN, which will allow earlier symptom management.

PMID- 28743662
TI  - Community Game Day: Using an End-of-Life Conversation Game to Encourage Advance
      Care Planning.
AB  - CONTEXT: Advance care planning (ACP) is an important process that involves
      discussing and documenting one's values and preferences for medical care,
      particularly end-of-life treatments. OBJECTIVES: This convergent, mixed-methods
      study assessed whether an end-of-life conversation card game is an acceptable and
      effective means for performing ACP for patients with chronic illness and/or their
      caregivers when deployed in a community setting. METHODS: Twenty-two games (n =
      93 participants) were held in community settings surrounding Hershey, PA in 2016.
      Participants were recruited using random sampling from patient databases and also
      convenience sampling (i.e., flyers). Quantitative questionnaires and qualitative
      focus group interviews were administered to assess the game experience and
      subsequent performance of ACP behaviors. RESULTS: Both quantitative and
      qualitative data found that Community Game Day was a well-received, positive
      experience for participants and 75% of participants performed ACP within three
      months post-intervention. CONCLUSIONS: These findings suggest that using a
      conversation game during community outreach is a useful approach for engaging
      patients and caregivers in ACP. The convergence of quantitative and qualitative
      data strongly supports the continued investigation of the game in randomized
      controlled trials.

PMID- 28743663
TI  - The variant of pri-mir-26a-1 polymorphism is associated with decreased risk of
      betel quid-related oral premalignant lesions and oral squamous cell carcinoma.
AB  - OBJECTIVES: This case-control study evaluated the association of the single
      nucleotide polymorphism rs7372209 (T>C) in pri-mir-26a-1 with the risk and
      progression of betel quid (BQ)-related oral premalignant lesions (OPLs) and oral
      squamous cell carcinoma (OSCC). STUDY DESIGN: In total, 597 BQ chewers were
      recruited: 196 healthy controls, 241 patients with OPLs, and 160 patients with
      OSCC. Genotypes were determined using the TaqMan real-time assay. RESULTS: The
      C/T + T/T genotypes and T allele in pri-mir-26a-1 were correlated with a
      decreased risk of BQ-related OPLs (P = .038 and .005, respectively), oral
      leukoplakia (P = .01 and .001, respectively), and advanced-stage OSCC (P = .021
      and .004, respectively). The effects of the C/T + T/T genotypes and T allele on
      the decreased risk of OPLs were potent in the older age group (both Pinteraction
      < .001), heavy smokers (Pinteraction <= .003 and .006, respectively) and alcohol
      drinkers (Pinteraction <= .004 and .001, respectively). Furthermore, among
      patients with OSCC, the C/T + T/T genotypes and T allele were associated with a
      decreased risk of advanced pathologic stage (P = .032) and lymph node involvement
      (P = .017). CONCLUSIONS: BQ chewers carrying the T allele or C/T + T/T genotypes
      in pri-mir-26a-1 may have a decreased risk of oral leukoplakia, OPLs, and
      advanced-stage OSCC.

PMID- 28743664
TI  - Comparative analysis of imaging techniques for diagnostic accuracy of peri
      implant bone defects: a meta-analysis.
AB  - OBJECTIVE: The aim of this study was to systematically review the literature
      regarding diagnostic accuracy of imaging techniques in detecting peri-implant
      bone defects. STUDY DESIGN: The search was performed in 8 electronic databases
      from April to May 2016 and updated in September 2016. Studies that assessed
      imaging techniques to detect peri-implant bone defects were analyzed. RESULTS:
      The search yielded 680 articles published from 1991 to 2016. Of these, 12 studies
      were considered eligible for this review. The selected studies evaluated the use
      of cone beam computed tomography (CBCT), intraoral radiography (IR), computed
      tomography, and panoramic radiography. The sensitivity for CBCT was 59%, whereas
      the specificity was 67%. For IR, the sensitivity was 60%, and the specificity was
      59%. Area under the curve values in receiver operating characteristic (ROC)
      analysis were 69% for CBCT and 63% for IR. For CBCT, the highest value for
      positive predictive value was 0.94, negative predictive value was 0.98, positive
      likelihood ratio was 21.3, and negative likelihood ratio was 1.28. For IR, the
      highest positive predictive value was 1.0, negative predictive value 1.0,
      positive likelihood ratio 50.0, and negative likelihood ratio 0.70. The highest
      diagnostic odds ratio was 80 for CBCT and 4.45 for IR. No conclusion could be
      drawn for additional techniques. CONCLUSIONS: Both CBCT and IR showed a
      clinically acceptable performance for assessing peri-implant bone defects.

PMID- 28743665
TI  - AAOM Clinical Practice Statement Subject: Medication-induced Oral Reactions.

PMID- 28743666
TI  - Biological significance of 5-hydroxymethylcytosine in oral epithelial dysplasia
      and oral squamous cell carcinoma.
AB  - OBJECTIVES: The aim of this study was to determine the levels of 5
      hydroxylmethylcytosine (5-hmC) in oral epithelial dysplasia (OED) and oral
      squamous cell carcinoma (OSCC) compared with those in benign, reactive
      inflammatory lesions and to explore whether DNA hydroxymethylation may serve as a
      novel biomarker for early diagnosis and prognosis of OSCC. STUDY DESIGN: The
      study included normal mucosa from uninvolved margins of 9 fibromas, 10 oral
      lichen planus, 15 OED, and 23 OSCC. Cultured human keratinocyte lines from benign
      oral mucosa, OED, and OSCC, as well as a murine model in which OSCC was induced
      with 4-nitroquinoline-1-oxide, were also evaluated. RESULTS: Progressive loss of
      5-hmC from benign oral mucosal lesions to OED and OSCC was documented in patient
      samples. Decreased levels in 5-hmC that typify OED and OSCC were also detectable
      in human cell lines. Moreover, we characterized similar alterations in 5-hmC in
      an animal model of OED/OSCC. CONCLUSIONS: This study demonstrated that 5-hmC
      distinguishes OED and OSCC from benign lesions with high sensitivity and
      specificity. Consequently, loss of 5-hmC may be useful for the diagnosis of OED
      with potential implications for therapy of OSCC.

PMID- 28743667
TI  - Integrative analysis of mRNA and miRNA expression profiles in oral lichen planus:
      preliminary results.
AB  - OBJECTIVE: Oral lichen planus (OLP), a chronic inflammatory disease of unknown
      etiology, is considered a potentially malignant oral disorder. The aim of the
      present study was to analyze candidate microRNAs (miRNAs) and genes from patients
      with OLP and healthy controls (HCs). STUDY DESIGN: Biopsy specimens of the oral
      mucosa were collected from patients with OLP (n = 9) and from HCs (n = 4).
      Differentially expressed miRNAs and differentially expressed genes were screened
      by using next-generation sequencing with DESeq and edgeR software algorithms.
      RESULTS: A total of 94 differentially expressed miRNAs and 599 differentially
      expressed genes were detected in OLP. Potential regulatory miRNAs and genes were
      obtained by analyzing miRNA-messenger RNA networks. Of these, 5 downregulated
      miRNAs-Hsa-miR-135 a-5 p (P = .33), hsa-miR-128-3 p (P = .03), hsa-miR-218-5 p (P
      = .01), hsa-miR-125 a-5 p (P = .01), and hsa-let-7 e-5 p (P = .04)-were the most
      promising biomarkers in patients with OLP compared with HCs. The identified
      differentially expressed genes were significantly enriched in "inflammatory"
      events and immune-related terms through Kyoto Encyclopedia of Genes and Genomes
      and Gene Ontology analysis. CONCLUSIONS: The integrative analysis of messenger
      RNA and miRNA profiles provides important information to elucidate gene
      expression mechanisms and a comprehensive perspective to study the etiology and
      pathogenesis of OLP.

PMID- 28743668
TI  - A new haplotype of the coconut rhinoceros beetle, Oryctes rhinoceros, has escaped
      biological control by Oryctes rhinoceros nudivirus and is invading Pacific
      Islands.
AB  - The coconut rhinoceros beetle (CRB; Oryctes rhinoceros) is a major pest of
      coconut and oil palm, but the discovery and release of Oryctes rhinoceros
      nudivirus (OrNV) in the 1960s and 70s suppressed the pest such that no new
      invasions of uninfested islands by CRB were reported for over 30years after
      implementation of the biocontrol programme. Surprisingly, a highly damaging
      outbreak was reported from Guam (2007), which could not be controlled by OrNV.
      Subsequently, new invasions have been reported from Port Moresby, Papua New
      Guinea (2009); O'ahu, Hawai'i (2013); and Honiara, Solomon Islands (2015). We
      have found that all of these outbreaks have been caused by a previously
      unrecognized haplotype, CRB-G, which appears to be tolerant to OrNV. PCR analysis
      shows that OrNV is generally present at high incidence in established populations
      of CRB, but is generally absent from the invasive CRB-G populations. CRB-G from
      Guam was not susceptible to OrNV infection by oral delivery, but injection of the
      virus did cause mortality. Further genetic analysis shows that CRB populations
      can be divided into a number of clades that coincide with the endemic and
      invasive history of the beetle. Analysis suggests that CRB-G originated in Asia,
      though the precise location remains to be discovered.

PMID- 28743669
TI  - Relative abundance of deformed wing virus, Varroa destructor virus 1, and their
      recombinants in honey bees (Apis mellifera) assessed by kmer analysis of public
      RNA-Seq data.
AB  - Deformed wing virus (DWV) is a major pathogen of concern to apiculture, and
      recent reports have indicated the local predominance and potential virulence of
      recombinants between DWV and a related virus, Varroa destructor virus 1 (VDV).
      However, little is known about the frequency and titer of VDV and recombinants
      relative to DWV generally. In this study, I assessed the relative occurrence and
      titer of DWV and VDV in public RNA-seq accessions of honey bee using a rapid,
      kmer-based approach. Three recombinant types were detectable graphically and
      corroborated by de novo assembly. Recombination breakpoints did not disrupt the
      capsid-encoding region, consistent with previous reports, and both VDV- and DWV
      derived capsids were observed in recombinant backgrounds. High abundance of VDV
      kmers was largely restricted to recombinant forms. Non-metric multidimensional
      scaling identified genotypic clusters among DWV isolates, which was corroborated
      by read mapping and consensus generation. The recently described DWV-C lineage
      was not detected in the searched accessions. The data further highlight the
      utility of high-throughput sequencing to monitor viral polymorphisms and
      statistically test biological predictors of titer, and point to the need for
      consistent methodologies and sampling schemes.

PMID- 28743670
TI  - Xuefu Zhuyu decoction ameliorates obesity, hepatic steatosis, neuroinflammation,
      amyloid deposition and cognition impairment in metabolically stressed
      APPswe/PS1dE9 mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic syndrome and vascular dysfunction was
      suggested to be the risk factors for Alzheimer's disease (AD). Xuefu Zhuyu
      decoction (XZD) is a traditional Chinese medicine used to treat metabolic
      syndrome and cardiac-cerebral vascular disease. The effects of XZD on
      ameliorating metabolic syndrome, amyloid-related pathologies and cognitive
      impairment in an animal model of AD with metabolic stress was investigated.
      MATERIALS AND METHOD: The animal model of AD with metabolic stress was created by
      administrating high-fat diet and a low-dose injection of streptozotocin prior to
      the appearance of senile plaques in APP/PS1 transgenic mice. The diabesity
      associated metabolic changes and AD-related pathological alterations were
      examined. RESULTS: We found that XZD reduced body weight, insulin and leptin
      level, HOMA-IR, hepatic triglyceride, serum Abeta42 in the metabolic stressed AD
      animal. XZD also ameliorated oral glucose tolerant, Abeta deposition, astrocyte
      and microglia activation in the vicinity of plaques, and nesting behavior in the
      metabolic stressed AD animal. CONCLUSION: The results of this study suggest that
      XZD is able to reduce the peripheral metabolic stress-mediated vascular
      hypoperfusion, neuroinflammation and AD-related pathology in APP/PS1 mice.

PMID- 28743671
TI  - Impact of Gender Disparities on Short-Term and Long-Term Patient Reported
      Outcomes and Satisfaction Measures After Elective Lumbar Spine Surgery: A Single
      Institutional Study of 384 Patients.
AB  - BACKGROUND: There is a paucity of data determining the impact that gender
      disparities have on spine outcomes, particularly perception of health and
      satisfaction. The aim of this study was to determine whether there is a
      difference in 3-month and 1-year patient-reported outcomes and satisfaction after
      elective lumbar spine surgery. METHODS: This was a retrospectively analyzed study
      from a maintained prospective database of 384 patients who underwent elective
      lumbar spine surgery. Patients were categorized by gender (men, n = 199; women, n
      = 185). Patient-reported outcome instruments (Oswestry disability index, visual
      analogue scale-back pain/leg pain, EuroQol visual analogue scale, and EuroQol 5
      dimensions questionnaire) were completed before surgery, then at 3 and 12 months
      after surgery along with patient satisfaction measures. RESULTS: Baseline patient
      demographics, comorbidities, and operative variables were similar between both
      cohorts. The female cohort had a slightly longer hospital stay than male cohort
      (P = 0.007). Baseline patient-reported outcome measures were different between
      both cohorts, with female patients having more Oswestry disability index (23.8
      vs. 20.4; P <= 0.0001) and visual analogue scale-back pain (7.2 vs. 6.2; P =
      0.0004), and a lower EuroQol 5 dimensions questionnaire (0.34 vs. 0.49; P =
      0.0001) compared with the male cohort. At 1-year follow-up, the male cohort had a
      significantly more mean change in visual analogue scale-leg pain (-3.9 vs. -2.8;
      P = 0.04) and trended to have more mean change in visual analogue scale-back pain
      (-3.4 vs. -2.5; P = 0.06) and EuroQol visual analogue scale (8.6 vs. 3.4; P =
      0.054) scores compared with the female cohort. At 1-year a significantly more
      portion in the male cohort found that surgery met their expectations compared
      with the female cohort (65.0% vs. 49.5%; P = 0.02). CONCLUSIONS: Our study
      suggests that there may be differences in perception of health, pain, and
      disability between men and women at baseline, short-term and long-term follow-up
      that may influence overall patient satisfaction.

PMID- 28743672
TI  - Membrane-bound human orphan cytochrome P450 2U1: Sequence singularities,
      construction of a full 3D model, and substrate docking.
AB  - BACKGROUND: Human cytochrome P450 2U1 (CYP2U1) is an orphan CYP that exhibits
      several distinctive characteristics among the 57 human CYPs with a highly
      conserved sequence in almost all living organisms. METHODS: We compared its
      protein sequence with those of the 57 human CYPs and constructed a 3D structure
      of a full-length CYP2U1 model bound to a POPC membrane. We also performed docking
      experiments of arachidonic acid (AA) and N-arachidonoylserotonin (AS) in this
      model. RESULTS: The protein sequence of CYP2U1 displayed two unique
      characteristics when compared to those of the human CYPs, the presence of a
      longer N-terminal region upstream of the putative trans-membrane helix (TMH)
      containing 8 proline residues, and of an insert of about 20 amino acids
      containing 5 arginine residues between helices A' and A. Its N-terminal part
      upstream of TMH involved an additional short terminal helix, in a manner similar
      to what was reported in the crystal structure of Saccharomyces cerevisiae CYP51.
      Our model also showed a specific interaction between the charged residues of
      insert AA' and phosphate groups of lipid polar heads, suggesting a possible role
      of this insert in substrate recruitment. Docking of AA and AS in this model
      showed these substrates in channel 2ac, with the terminal alkyl chain of AA or
      the indole ring of AS close to the heme, in agreement with the reported CYP2U1
      catalyzed AA and AS hydroxylation regioselectivities. MAJOR CONCLUSION AND
      GENERAL SIGNIFICANCE: This model should be useful to find new endogenous or
      exogenous CYP2U1 substrates and to interpret the regioselectivity of their
      hydroxylation.

PMID- 28743673
TI  - Genomic landscape of copy number variation and copy neutral loss of
      heterozygosity events in equine sarcoids reveals increased instability of the
      sarcoid genome.
AB  - Although they are the most common neoplasms in equids, sarcoids are not fully
      characterized at the molecular level. Therefore, the objective of this study was
      to characterize the landscape of structural rearrangements, such as copy number
      variation (CNV) and copy neutral loss of heterozygosity (cnLOH), in the genomes
      of sarcoid tumor cells. This information will not only broaden our understanding
      of the characteristics of this genome but will also improve the general knowledge
      of this tumor and the mechanisms involved in its generation. To this end, Equine
      SNP64K Illumina microarrays were applied along with bioinformatics tools
      dedicated for signal intensity analysis. The analysis revealed increased
      instability of the genome of sarcoid cells compared with unaltered skin tissue
      samples, which was manifested by the prevalence of CNV and cnLOH events. Many of
      the identified CNVs overlapped with the other research results, but the
      simultaneously observed variability in the number and sizes of detected
      aberrations indicated a need for further studies and the development of more
      reliable bioinformatics algorithms. The functional analysis of genes co-localized
      with the identified aberrations revealed that these genes are engaged in vital
      cellular processes. In addition, a number of these genes directly contribute to
      neoplastic transformation. Furthermore, large numbers of cnLOH events identified
      in the sarcoids suggested that they may play no less significant roles than CNVs
      in the carcinogenesis of this tumor. Thus, our results indicate the importance of
      cnLOH and CNV in equine sarcoid oncogenesis and present a direction of future
      research.

PMID- 28743674
TI  - The role of alternative splicing coupled to nonsense-mediated mRNA decay in human
      disease.
AB  - Alternative pre-mRNA splicing (AS) affects gene expression as it generates
      proteome diversity. Nonsense-mediated mRNA decay (NMD) is a surveillance pathway
      that recognizes and selectively degrades mRNAs carrying premature translation
      termination codons (PTCs), preventing the production of truncated proteins that
      could result in disease. Several studies have also implicated NMD in the
      regulation of steady-state levels of physiological mRNAs. In addition, it is
      known that several regulated AS events do not lead to generation of protein
      products, as they lead to transcripts that carry PTCs and thus, they are
      committed to NMD. Indeed, an estimated one-third of naturally occurring,
      alternatively spliced mRNAs is targeted for NMD, being AS coupled to NMD (AS-NMD)
      an efficient strategy to regulate gene expression. In this review, we will focus
      on how AS mechanism operates and how can be coupled to NMD to fine-tune gene
      expression levels. Furthermore, we will demonstrate the physiological
      significance of the interplay among AS and NMD in human disease, such as cancer
      and neurological disorders. The understanding of how AS-NMD orchestrates
      expression of vital genes is of utmost importance for the advance in diagnosis,
      prognosis and treatment of many human disorders.

PMID- 28743675
TI  - Role of nonsense-mediated decay and nonsense-associated altered splicing in the
      mRNA pattern of two new alpha-thalassemia mutants.
AB  - alpha-thalassemia is a common disease characterized mainly by deletion mutants.
      We identified two new alpha-thalassemia pointform mutants: alpha1cod22 GGC>GGT
      Gly>Gly creating a 5' splicing sequence and alpha1cod23 GAG>TAG Glu>stop. We
      performed qualitative and semi-quantitative analysis of the mRNA molecules, from
      carriers' blood, to define the molecular mechanisms giving rise to the
      thalassemia phenotype. In vitro analysis using alpha-globin constructs and
      cycloheximide was performed to evaluate if the mutants are substrates of nonsense
      mediated mRNA decay (NMD). In the alpha1cod22 GGC>GGT the new 5' splicing site in
      exon 1 completely substitutes the normal one. We demonstrated the presence of
      mRNA decay as the abnormally spliced mRNA was consistent in the nucleus,
      partially degraded in the cytoplasm of cultured cells, but only 2.8% in the
      reticulocytes. The analysis of the alphacod23 transcript showed an escape from
      the NMD as for the human beta-globin transcript with nonsense mutations in the
      first exon: the anomalous mRNA was reduced in the nucleus, followed by only a
      slight lowering from 32% to 27% of the normal alpha1 mRNA in the reticulocytes.
      In both the mutants we showed a moderate sensitivity to the NMD assay and we
      speculate the activation of other RNA surveillance mechanisms for the alphacod22
      mutant. No activation of cryptic splice sites was detected and no role could be
      assigned to the nonsense-associated altered splicing. Studies on transcripts from
      patient cells represent a very useful approach providing considerable information
      about the processes occuring in vivo.

PMID- 28743676
TI  - Northern Trek: The Spread of Ixodes scapularis into Canada.

PMID- 28743677
TI  - Maiden Voyage of the Collaborative Cross Mouse: Exploring Variability in Animals'
      Response to Perchloroethylene.

PMID- 28743678
TI  - The Saliva Exposome for Monitoring of Individuals' Health Trajectories.
AB  - BACKGROUND: There is increasing evidence that environmental, rather than genetic,
      factors are the major causes of most chronic diseases. By measuring entire
      classes of chemicals in archived biospecimens, exposome-wide association studies
      (EWAS) are being conducted to investigate associations between a myriad of
      exposures received during life and chronic diseases. OBJECTIVES: Because the
      intraindividual variability in biomarker levels, arising from changes in
      environmental exposures from conception onwards, leads to attenuation of exposure
      disease associations, we posit that saliva can be collected repeatedly in
      longitudinal studies to reduce exposure-measurement errors in EWAS. METHODS: From
      the literature and an open-source saliva-metabolome database, we obtained
      concentrations of 1,233 chemicals that had been detected in saliva. We connected
      salivary metabolites with human metabolic pathways and PubMed Medical Subject
      Heading (MeSH) terms, and performed pathway enrichment and pathway topology
      analyses. RESULTS: One hundred ninety-six salivary metabolites were mapped into
      49 metabolic pathways and connected with human metabolic diseases, central
      nervous system diseases, and neoplasms. We found that the saliva exposome
      represents at least 14 metabolic pathways, including amino acid metabolism, TCA
      cycle, gluconeogenesis, glutathione metabolism, pantothenate and CoA
      biosynthesis, and butanoate metabolism. CONCLUSIONS: Saliva contains molecular
      information worthy of interrogation via EWAS. The simplicity of specimen
      collection suggests that saliva offers a practical alternative to blood for
      measurements that can be used to characterize individual exposomes.
      https://doi.org/10.1289/EHP1011.

PMID- 28743679
TI  - Exploring the Association Between Self-Reported Asthma Impact and Fitbit-Derived
      Sleep Quality and Physical Activity Measures in Adolescents.
AB  - BACKGROUND: Smart wearables such as the Fitbit wristband provide the opportunity
      to monitor patients more comprehensively, to track patients in a fashion that
      more closely follows the contours of their lives, and to derive a more complete
      dataset that enables precision medicine. However, the utility and efficacy of
      using wearable devices to monitor adolescent patients' asthma outcomes have not
      been established. OBJECTIVE: The objective of this study was to explore the
      association between self-reported sleep data, Fitbit sleep and physical activity
      data, and pediatric asthma impact (PAI). METHODS: We conducted an 8-week pilot
      study with 22 adolescent asthma patients to collect: (1) weekly or biweekly
      patient-reported data using the Patient-Reported Outcomes Measurement Information
      System (PROMIS) measures of PAI, sleep disturbance (SD), and sleep-related
      impairment (SRI) and (2) real-time Fitbit (ie, Fitbit Charge HR) data on physical
      activity (F-AM) and sleep quality (F-SQ). To explore the relationship among the
      self-reported and Fitbit measures, we computed weekly Pearson correlations among
      these variables of interest. RESULTS: We have shown that the Fitbit-derived sleep
      quality F-SQ measure has a moderate correlation with the PROMIS SD score (average
      r=-.31, P=.01) and a weak but significant correlation with the PROMIS PAI score
      (average r=-.18, P=.02). The Fitbit physical activity measure has a negligible
      correlation with PAI (average r=.04, P=.62). CONCLUSIONS: Our findings support
      the potential of using wrist-worn devices to continuously monitor two important
      factors-physical activity and sleep-associated with patients' asthma outcomes and
      to develop a personalized asthma management platform.

PMID- 28743680
TI  - Internet-Based Assessment of Oncology Health Care Professional Learning Style and
      Optimization of Materials for Web-Based Learning: Controlled Trial With Concealed
      Allocation.
AB  - BACKGROUND: Precision medicine has resulted in increasing complexity in the
      treatment of cancer. Web-based educational materials can help address the needs
      of oncology health care professionals seeking to understand up-to-date treatment
      strategies. OBJECTIVE: This study aimed to assess learning styles of oncology
      health care professionals and to determine whether learning style-tailored
      educational materials lead to enhanced learning. METHODS: In all, 21,465 oncology
      health care professionals were invited by email to participate in the fully
      automated, parallel group study. Enrollment and follow-up occurred between July
      13 and September 7, 2015. Self-enrolled participants took a learning style survey
      and were assigned to the intervention or control arm using concealed alternating
      allocation. Participants in the intervention group viewed educational materials
      consistent with their preferences for learning (reading, listening, and/or
      watching); participants in the control group viewed educational materials typical
      of the My Cancer Genome website. Educational materials covered the topic of
      treatment of metastatic estrogen receptor-positive (ER+) breast cancer using
      cyclin-dependent kinases 4/6 (CDK4/6) inhibitors. Participant knowledge was
      assessed immediately before (pretest), immediately after (posttest), and 2 weeks
      after (follow-up test) review of the educational materials. Study statisticians
      were blinded to group assignment. RESULTS: A total of 751 participants enrolled
      in the study. Of these, 367 (48.9%) were allocated to the intervention arm and
      384 (51.1%) were allocated to the control arm. Of those allocated to the
      intervention arm, 256 (69.8%) completed all assessments. Of those allocated to
      the control arm, 296 (77.1%) completed all assessments. An additional 12
      participants were deemed ineligible and one withdrew. Of the 552 participants,
      438 (79.3%) self-identified as multimodal learners. The intervention arm showed
      greater improvement in posttest score compared to the control group (0.4 points
      or 4.0% more improvement on average; P=.004) and a higher follow-up test score
      than the control group (0.3 points or 3.3% more improvement on average; P=.02).
      CONCLUSIONS: Although the study demonstrated more learning with learning style
      tailored educational materials, the magnitude of increased learning and the
      largely multimodal learning styles preferred by the study participants lead us to
      conclude that future content-creation efforts should focus on multimodal
      educational materials rather than learning style-tailored content.

PMID- 28743681
TI  - Development and Testing of an Intelligent Pain Management System (IPMS) on Mobile
      Phones Through a Randomized Trial Among Chinese Cancer Patients: A New Approach
      in Cancer Pain Management.
AB  - BACKGROUND: Cancer has become increasingly prevalent in China over the past few
      decades. Among the factors that determine the quality of life of cancer patients,
      pain has commonly been recognized as a most critical one; it could also lead to
      the ineffective treatment of the cancer. Driven by the need for better pain
      management for cancer patients, our research team developed a mobile-based
      Intelligent Pain Management System (IPMS). OBJECTIVE: Our objective was to
      design, develop, and test the IPMS to facilitate real-time pain recording and
      timely intervention among cancer patients with pain. The system's usability,
      feasibility, compliance, and satisfaction were also assessed. METHODS: A sample
      of 46 patients with cancer pain symptoms were recruited at the Oncology Center of
      Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine,
      Chongming Branch (hereinafter referred to as "the Oncology Center"). In a
      pretest, participants completed a pain management knowledge questionnaire and
      were evaluated using the baseline cancer pain assessment and Karnofsky
      Performance Status (KPS) evaluation. The participants were then randomly assigned
      into two groups (the trial group and the control group). After a 14-day trial
      period, another round of cancer pain assessment, KPS evaluation and pain
      management knowledge assessment were repeated. In the trial group, the data were
      fully automatically collected by the IPMS. In the control group, the data were
      collected using conventional methods, such as phone interviews or door-to-door
      visits by physicians. The participants were also asked to complete a satisfaction
      questionnaire on the use of the IPMS. RESULTS: All participants successfully
      completed the trial. First, the feasibility of IPMS by observing the number of
      daily pain assessments recorded among patients was assessed. Second, the users'
      satisfaction, effectiveness of pain management, and changes in the quality of
      their lives were evaluated. All the participants gave high satisfaction score
      after they used IMPS. Both groups reported similar pain scores and KPS scores at
      the baseline. At the end of the trial, the mean pain score of the trial group was
      significantly lower than of the control group (P<.001). The ending KPS score of
      the trial group was significantly higher than of the control group (P<.001). The
      improvement of pain management knowledge score in the trial group was more
      pronounced than that in the control group (P<.001). CONCLUSIONS: This study
      provided preliminary data to support the potentials of using IPMS in cancer pain
      communication between patients and doctors and to provide real-time supportive
      intervention on a convenient basis at a low cost. Overall, the IPMS can serve as
      a reliable and effective approach to control cancer pain and improve quality of
      life for patients with cancer pain. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT02765269; http://clinicaltrials.gov/ct2/show/NCT02765269 (Archived by WebCite
      at http://www.webcitation.org/6rnwsgDgv).

PMID- 28743682
TI  - Estimating Heart Rate, Energy Expenditure, and Physical Performance With a Wrist
      Photoplethysmographic Device During Running.
AB  - BACKGROUND: Wearable sensors enable long-term monitoring of health and wellbeing
      indicators. An objective evaluation of sensors' accuracy is important, especially
      for their use in health care. OBJECTIVE: The aim of this study was to use a wrist
      worn optical heart rate (OHR) device to estimate heart rate (HR), energy
      expenditure (EE), and maximal oxygen intake capacity (VO2Max) during running and
      to evaluate the accuracy of the estimated parameters (HR, EE, and VO2Max) against
      golden reference methods. METHODS: A total of 24 healthy volunteers, of whom 11
      were female, with a mean age of 36.2 years (SD 8.2 years) participated in a
      submaximal self-paced outdoor running test and maximal voluntary exercise test in
      a sports laboratory. OHR was monitored with a PulseOn wrist-worn
      photoplethysmographic device and the running speed with a phone GPS sensor. A
      physiological model based on HR, running speed, and personal characteristics
      (age, gender, weight, and height) was used to estimate EE during the maximal
      voluntary exercise test and VO2Max during the submaximal outdoor running test.
      ECG-based HR and respiratory gas analysis based estimates were used as golden
      references. RESULTS: OHR was able to measure HR during running with a 1.9% mean
      absolute percentage error (MAPE). VO2Max estimated during the submaximal outdoor
      running test was closely similar to the sports laboratory estimate (MAPE 5.2%).
      The energy expenditure estimate (n=23) was quite accurate when HR was above the
      aerobic threshold (MAPE 6.7%), but MAPE increased to 16.5% during a lighter
      intensity of exercise. CONCLUSIONS: The results suggest that wrist-worn OHR may
      accurately estimate HR during running up to maximal HR. When combined with
      physiological modeling, wrist-worn OHR may be used for an estimation of EE,
      especially during higher intensity running, and VO2Max, even during submaximal
      self-paced outdoor recreational running.

PMID- 28743683
TI  - Cross-Sectional Study of Chronic Obstructive Pulmonary Disease Prevalence Among
      Smokers, Ex-Smokers, and Never-Smokers in Almaty, Kazakhstan: Study Protocol.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is significantly
      underdiagnosed in Kazakhstan, and there is no previously conducted study on COPD
      prevalence in the country. OBJECTIVE: The purpose of this study is to assess the
      prevalence of COPD among individuals aged 40 to 59 years based on results of
      spirometry before and after bronchodilator, presence of structural changes in the
      lungs (emphysema, inflammatory changes, and thickening of the walls of the large
      and small airways) detected by computer tomography, and the symptoms of COPD. The
      study has 3 study groups: smokers of conventional cigarettes, those who had quit
      smoking 1 to 5 years ago, and those who haven't smoked cigarettes. METHODS: This
      is an observational study with a cross-sectional design among individuals aged 40
      to 59 years in Almaty, Kazakhstan. The sample of 900 individuals of both sexes
      contains 500 smokers, 200 ex-smokers, and 200 never-smokers. Study measures
      include spirometry, chest computed tomography, electrocardiography, physical
      exams, laboratory testing of serum, anthropometry, and 6-minute walk test. Data
      are collected by computer-assisted personal interviewing with tablets. The
      questionnaire was designed to explore possible COPD risk factors including
      history of smoking, current smoking, level of smoking exposure (in pack-years),
      passive smoking, occupational and environmental hazards, and covariates: age,
      gender, ethnicity, education, occupation, and self-reported morbidity. COPD
      Assessment Test (CAT) is used to collect information about COPD symptoms.
      RESULTS: We have completed the participant recruitment and study procedures.
      Currently, we are working on data processing and data analysis. The authors
      anticipate the preliminary results should be available by September 2017. Study
      results will be published in peer-reviewed scientific journals. CONCLUSIONS: This
      is the first study in Kazakhstan that assesses prevalence of COPD and its
      comorbidities in the adult population aged 40 to 59 years. The results of the
      study will be useful for improving COPD preventive measures, better COPD
      screening, identification, and registration. Findings of the study will also
      contribute to global knowledge on the epidemiology of COPD. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02926534; https://clinicaltrials.gov/ct2/show/NCT02926534
      (Archived by WebCite at http://www.webcitation.org/6rjwGsPOZ).

PMID- 28743684
TI  - Cataract surgery is cost effective and should not be rationed, says NICE.

PMID- 28743685
TI  - David Oliver: When "resilience" becomes a dirty word.

PMID- 28743686
TI  - Patients harmed by mesh implants address emotional parliamentary meeting.

PMID- 28743687
TI  - TP73 DNA methylation and upregulation of DeltaNp73 are associated with an adverse
      prognosis in breast cancer.
AB  - AIM: Accumulated evidence suggests that aberrant methylation of the TP73 gene and
      increased levels of DeltaNp73 in primary tumours correlate with poor prognosis.
      However, little is known regarding the transcriptional and functional regulation
      of the TP73 gene in breast cancer. The aim of the present study was to determine
      the expression of the DeltaNp73 isoform, its relationship with DNA methylation of
      TP73 and their clinical prognostic significance in breast cancer patients.
      METHODS: TP73 gene methylation was studied in TCGA datasets and in 70 invasive
      ductal breast carcinomas (IDCs). The expression of p73 isoforms was evaluated by
      immunohistochemistry (IHC) and Western blot and correlated with
      clinicopathological variables and clinical outcome. RESULTS: We observed that the
      methylation of diverse CpG islands of TP73 differed significantly between
      molecular subtypes. An inverse correlation was found between p73 protein
      expression and the methylation status of the TP73 gene. The expression of exon 3'
      of p73 (only expressed in DeltaNp73) was significantly higher in patients with
      wild-type p53. Immunohistochemical analysis revealed that all p73 isoforms were
      localised in both the nuclear and cytoplasmic compartments. We confirmed a
      positive association between the expression of ?Np73 and high histological grade.
      CONCLUSIONS: Our findings suggest that high expression of DeltaNp73 could be used
      to determine the aggressiveness of IDCs and could be incorporated in the
      pathologist's report.

PMID- 28743688
TI  - The effects of postmortem CT scanning all cases entering a UK public mortuary: a
      3-month pilot.

PMID- 28743689
TI  - Explorations in statistics: the assumption of normality.
AB  - Learning about statistics is a lot like learning about science: the learning is
      more meaningful if you can actively explore. This twelfth installment of
      Explorations in Statistics explores the assumption of normality, an assumption
      essential to the meaningful interpretation of a t test. Although the data
      themselves can be consistent with a normal distribution, they need not be.
      Instead, it is the theoretical distribution of the sample mean or the theoretical
      distribution of the difference between sample means that must be roughly normal.
      The most versatile approach to assess normality is to bootstrap the sample mean,
      the difference between sample means, or t itself. We can then assess whether the
      distributions of these bootstrap statistics are consistent with a normal
      distribution by studying their normal quantile plots. If we suspect that an
      inference we make from a t test may not be justified-if we suspect that the
      theoretical distribution of the sample mean or the theoretical distribution of
      the difference between sample means is not normal-then we can use a permutation
      method to analyze our data.

PMID- 28743690
TI  - Educational leadership: benefits of stepping outside the classroom.
AB  - Although most educators have their greatest impact in the classroom, the
      increased need for diverse learning activities has created new opportunities for
      leadership. Moreover, many Tenure and Promotion Committees are finding that it is
      no longer sufficient to consider only lecture hours when evaluating a faculty
      member's contributions to the teaching mission of an institution. Accordingly,
      the career path for an educator in a college or professional school is evolving.
      A newly recruited faculty member may start out with traditional classroom
      responsibilities, but activities other than lecture, such as flipped classrooms,
      online resources, and peer-to-peer teaching, may be quickly added to the mix. As
      faculty members gain experience, they often progress to positions of curriculum
      design or program review within an institution. Similarly, there is a need for
      administrators who have participated in a variety of learning activities, and
      schools frequently recruit for these positions from faculty with such exposure.
      Many senior faculty members leverage this expertise to regional or national
      levels by authoring textbooks and online materials or serving on advisory boards,
      review committees, and governance in professional societies and funding agencies.
      Excelling in these leadership opportunities can have a profound effect on the
      success of promotion and tenure applications, and they reward a skill set that
      extends beyond the teaching and organization needed in the classroom.

PMID- 28743691
TI  - Understanding factors affecting participation in online formative quizzes: an
      interview study.
AB  - A positive correlation between performance and participation in formative quizzes
      and final summative examinations has been reported many times. The goal of the
      present interview study was to construct a model to explain why students may
      elect not to engage with formative assessment opportunities. Our medical school's
      preclinical curriculum has an established policy of offering weekly online
      quizzes in all courses during the first 2 yr. Quizzes do not count for credit.
      Semistructured interviews were recorded and transcribed verbatim, and a formal
      thematic analysis was applied. A total of 16 in-depth interviews were conducted,
      with 8 female and 8 male participants. Thematic analysis revealed four major
      interacting themes that we propose to converge to account for nonparticipation in
      quizzes: 1) inadequate feedback, 2) curriculum organization and student mistrust,
      3) time constraints, and 4) fear of judgment. We propose seven practice points to
      improve the effectiveness of formative assessment quizzes of medical knowledge.

PMID- 28743692
TI  - An IDeA for enhancing undergraduate research at rural primarily undergraduate
      institutions.
AB  - This study documents the efforts of the North Dakota (ND) IDeA Networks of
      Biomedical Research Excellence (INBRE) program to assist in the development of
      undergraduate research programs at four state-supported primarily undergraduate
      institutions (PUIs) in ND. The study was initiated in the 2004-2005 academic year
      and continues to the present. The study shows that gaining initial institutional
      support for undergraduate research was assisted by providing salary support for
      faculty involved in undergraduate research. Once research was ongoing, each
      institution evolved their own unique plan for the use of support from the ND
      INBRE. Undergraduate student researchers have prepared, presented, and defended
      their research results on 188 unique posters since initiation of the program,
      with many posters being presented at more than one meeting. PUI faculty have
      authored 35 peer-reviewed manuscripts. Evaluation has shown that over 95% of the
      undergraduate students performing research matriculated with their bachelor's
      degree. Career choices of 77.2% of these graduates was determined, and 37%
      pursued a career in the health professions. Of the students not pursuing a post
      baccalaureate degree, 81.2% chose careers directly linked to science. The study
      reinforces the concept that undergraduate research can be performed directly on
      the PUI campus and be of value in preparing the next generation of health
      professionals in research, service, and teaching.

PMID- 28743693
TI  - Can Facebook pages be a mode of blended learning to supplement in-class teaching
      in Saudi Arabia?
AB  - The aim of this study was to examine the potential of a self-designed Facebook
      page on Neuroscience, to supplement in-class teaching as a mode of blended
      learning. Posts were split into multiple choice questions (MCQs), general
      interest articles, neuroscience-related external links and resources, and lecture
      notes and PowerPoint presentations. The study was divided into three distinct
      phases: before, during, and after the Neuroscience block. Student responses were
      evaluated via a self-developed questionnaire. Grades achieved by students
      undertaking the block in 2015 and 2014 were recorded, as were the grades achieved
      by the same cohort in concurrent blocks in the same year of study. Results showed
      that ~80% of students reported that use of the page enhanced their overall
      subject knowledge and exam preparation. Highest page activity occurred during the
      Neuroscience block. Peak activity occurred directly before summative assessments,
      with MCQ posts having the highest impact. The cohort of students with access to
      the Facebook page achieved better grades in the block compared with the previous
      cohort, despite similar average performance in other subjects. We demonstrate the
      utility of Facebook as a powerful tool for undergraduate education, supplementing
      in-class teaching, and assisting in exam preparation, potentially increasing
      average student performance.

PMID- 28743694
TI  - Impact of surgical timing of postoperative ocular motility in orbital blowout
      fractures.
AB  - PURPOSE: To investigate the surgical timing postinjury in regard to ocular
      motility in patients with orbital-floor blowout fractures. METHODS: This study
      involved 197 eyes (92 right eyes and 105 left eyes) of 197 patients (154 males
      and 43 females, mean age: 29.0 years, range: 7-85 years) with pure orbital
      blowout fractures. All patients underwent surgical repair within 30 days
      postinjury and were followed up for 3 months or more postoperative (mean follow
      up period: 8.4 months, range: 3-59 months). Orbital blowout fractures were
      classified into one of three shapes: (1) trap-door fracture with muscle
      entrapment, (2) trap-door fracture with incarcerated tissue and (3) depressed
      fragment fracture. Ocular motility was estimated by percentage of Hess area ratio
      (HAR%) on the Hess chart at the final follow-up examination. In addition,
      correlations between postinjury surgical timing and HAR% were analysed. RESULTS:
      The mean postinjury surgical timing was 10.7+/-7.8 days (range: 0-30 days). The
      mean postoperative HAR% (92.9%+/-10.5%) was significantly improved compared with
      preoperative HAR% (73.5%+/-21.7%) (p<0.01). The mean postoperative HAR% (98.3%+/
      4.4%) of the orbital-floor trap-door fracture patients with incarcerated tissue
      who underwent surgical repair within 8 days postinjury was significantly better
      than that of the patients who underwent surgical repair after 8 days (94.2%+/
      5.8%) (p<0.01). CONCLUSIONS: Patients with orbital-floor trap-door blowout
      fractures with incarcerated tissue that were repaired within 8 days postinjury
      had better outcomes than those repaired after 8 days, and HAR% is a useful method
      to record orbital fracture surgical outcomes.

PMID- 28743696
TI  - Large case series documents chronic brain damage in players of American football.

PMID- 28743695
TI  - Ectopic application of the repressive histone modification H3K9me2 establishes
      post-zygotic reproductive isolation in Arabidopsis thaliana.
AB  - Hybrid seed lethality as a consequence of interspecies or interploidy
      hybridizations is a major mechanism of reproductive isolation in plants. This
      mechanism is manifested in the endosperm, a dosage-sensitive tissue supporting
      embryo growth. Deregulated expression of imprinted genes such as ADMETOS (ADM)
      underpin the interploidy hybridization barrier in Arabidopsis thaliana; however,
      the mechanisms of their action remained unknown. In this study, we show that ADM
      interacts with the AT hook domain protein AHL10 and the SET domain-containing
      SU(VAR)3-9 homolog SUVH9 and ectopically recruits the heterochromatic mark
      H3K9me2 to AT-rich transposable elements (TEs), causing deregulated expression of
      neighboring genes. Several hybrid incompatibility genes identified in Drosophila
      encode for dosage-sensitive heterochromatin-interacting proteins, which has led
      to the suggestion that hybrid incompatibilities evolve as a consequence of
      interspecies divergence of selfish DNA elements and their regulation. Our data
      show that imbalance of dosage-sensitive chromatin regulators underpins the
      barrier to interploidy hybridization in Arabidopsis, suggesting that reproductive
      isolation as a consequence of epigenetic regulation of TEs is a conserved feature
      in animals and plants.

PMID- 28743697
TI  - Child poverty: what should doctors do?

PMID- 28743698
TI  - High-Flow Nasal Cannula in Bronchiolitis: Modeling the Economic Effects of a Ward
      Based Protocol.
AB  - OBJECTIVES: High-flow nasal cannula (HFNC) use has increased in patients with
      bronchiolitis, with the majority of use restricted to the ICU. Broadening HFNC to
      the wards may have substantial economic implications. This study compares the
      cost of a standardized clinical pathway that permits HFNC use in the wards for
      patients with bronchiolitis with an ICU-only HFNC care model. METHODS: We
      constructed a decision analytic model to simulate 2 options for treating
      bronchiolitic patients: one in which HFNC is used in the wards (ward HFNC) and
      one in which HFNC is restricted to the ICU (ICU HFNC). The model inputs were
      based on patients admitted with bronchiolitis without major comorbidities between
      2010 and 2015. 1432 patients were included for analysis. We simulated 10 000
      patients for 5000 trials to assess parameter variability and sampling
      uncertainty, respectively. The primary outcome was average admission cost per
      patient. The secondary outcome was average length of stay (LOS) per patient.
      RESULTS: In the model, the average admission cost per patient for the ward HFNC
      group was $7020 (95% confidence interval [CI] $6840-$7194) compared with $7626
      (95% CI $7427-$7839) in the ICU HFNC group, with a net difference of $606 (95% CI
      $408-$795). The average LOS for the ward HFNC group was 2.29 days (95% CI 2.24
      2.33) compared with 2.61 days (95% CI 2.56-2.66) in the ICU HFNC group, with a
      net difference of 0.32 days (95% CI 0.27-0.37). CONCLUSIONS: Using HFNC in the
      ward for bronchiolitis may be cost-effective and may decrease LOS compared with
      ICU-only HFNC.

PMID- 28743699
TI  - Charlie Gard's parents end legal fight to keep son alive.

PMID- 28743700
TI  - Critical flicker frequency is diagnostic of minimal hepatic encephalopathy.
AB  - Minimal hepatic encephalopathy may affect up to 80% of cirrhotic patients, in the
      absence of overt hepatic encephalopathy. The objective of the study is to
      evaluate the accuracy of diagnosis of minimal hepatic encephalopathy with
      critical flicker frequency (CFF). The study was conducted on 180 patients with
      post hepatitis C liver cirrhosis and on 60 healthy subjects as control. Patients
      and controls were divided into four groups: group 1 (60), healthy individuals as
      a control group; group 2 (60), patients with liver cirrhosis (Child class A);
      group 3 (60), patients with liver cirrhosis (Child class B); and group 4 (60),
      patients with liver cirrhosis (Child class C). All participants were subjected to
      estimation of CFF, line drawing test, complete blood picture, liver functions,
      viral markers, and abdominal ultrasound. CFF detected abnormality in 90% of
      patients. Accuracy of CFF in differentiation of Child A from normal is 100%,
      Child B from normal is 100%, Child C from normal is 100%, Child A from Child B is
      80%, Child A from Child C is 100% and Child B from Child C is 100%, and it has
      higher accuracy than line drawing test. CFF is a simple, reliable and accurate
      method for the diagnosis of minimal hepatic encephalopathy. It is not influenced
      by the patient level of education.

PMID- 28743701
TI  - Correction for Chaftari et al., "A Novel Nonantibiotic Nitroglycerin-Based
      Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter
      Infections in Cancer Patients".

PMID- 28743703
TI  - Heavy drinking predicted to kill 63 000 people over the next five years.

PMID- 28743702
TI  - Progressive Dispersion of Azole Resistance in Aspergillus fumigatus: Fatal
      Invasive Aspergillosis in a Patient with Acute Myeloid Leukemia Infected with an
      A. fumigatus Strain with a cyp51A TR46 Y121F M172I T289A Allele.
AB  - Patients with hematologic malignancies as well as allogeneic hematopoietic stem
      cell transplantation (HSCT) patients are at high risk for invasive aspergillosis.
      Here, we report a culture- and autopsy-proven fatal invasive aspergillosis in an
      allogeneic HSTC patient which he developed despite posaconazole prophylaxis. The
      agent was determined to be an azole-resistant Aspergillus fumigatus strain
      bearing the cyp51A mutation combination TR46 Y121F M172I T289A. At increasing
      frequency, the azole resistance of A. fumigatus is being reported globally,
      limiting treatment options and complicating regimens.

PMID- 28743704
TI  - Photo Quiz: Motile Structures in the Stool of a Field Biologist.

PMID- 28743705
TI  - The Brief Case: False-Positive Rapid Malaria Antigen Test Result in a Returned
      Traveler.

PMID- 28743706
TI  - Closing the Brief Case: False-Positive Rapid Malaria Antigen Test Result in a
      Returned Traveler.

PMID- 28743707
TI  - Answer to August 2017 Photo Quiz.

PMID- 28743708
TI  - Tackling the great challenges in biology: Beyond evolution, defining the greatest
      challenges in biology is a challenge itself.

PMID- 28743709
TI  - Biology goes in the air: Unmanned aerial vehicles offer biologists an efficient
      tool for observation and sampling from a safe distance.

PMID- 28743710
TI  - Mitochondrial permeability transition, F1FO-ATPase and calcium: an enigmatic
      triangle.

PMID- 28743711
TI  - Proactive epigenesis and ethics.

PMID- 28743712
TI  - Response by the authors.

PMID- 28743713
TI  - Expanding the 3R principles: More rigour and transparency in research using
      animals.

PMID- 28743714
TI  - Incidental finding of a double orifice mitral valve in an elderly patient: value
      of 3D imaging.
AB  - : A rare isolated double orifice mitral valve (DOMV) was diagnosed in a 77-year
      old male patient, being assessed for surgical repair of the ascending aorta. This
      is a rare congenital abnormality, usually discovered as an incidental finding
      during investigation of other congenital heart defects. This case shows that a
      detailed assessment of all cardiac structures is necessary, not only in young
      patients, but also in the elderly population, to minimise the under-diagnosis of
      such rare anomalies. The use of 3D transthoracic echocardiography (TTE) has an
      increasingly significant role in establishing the diagnosis and extending the
      morphological and functional understanding of the anomaly. LEARNING POINTS:
      Thoroughly assessing all cardiac structures, in accordance with the minimum
      dataset guidelines for transthoracic echocardiography, ensures not only a
      comprehensive assessment of the primary indication for the scan, but also
      improves the detection of concomitant and otherwise unknown lesions. Despite
      falling under the category of congenital heart defects, several rare anomalies
      such as DOMV can be present in elderly patients, and the adult echocardiographer
      should have appropriate knowledge and awareness for detecting these conditions.
      3D TTE provides a comprehensive assessment of the morphology of DOMV, over and
      above the information obtained by 2D imaging.

PMID- 28743715
TI  - Circulatory and maturation kinetics of human monocyte subsets in vivo.

PMID- 28743716
TI  - How I monitor long-term and late effects after blood or marrow transplantation.
AB  - Blood or marrow transplantation (BMT) is used with curative intent for
      hematologic malignancies. Conditional on surviving the first 2 years after BMT, 5
      year survival generally exceeds 70%. However, the cumulative therapeutic
      exposures lead to premature onset of chronic health conditions, such that the 15
      year cumulative incidence of severe or life-threatening chronic health conditions
      exceeds 40%, resulting in premature mortality. The high burden of morbidity,
      coupled with a long latency between BMT and the development of chronic health
      conditions necessitates life-long risk-based monitoring of the BMT survivors. The
      issues of how and when to screen BMT survivors for therapy-related complications
      and exacerbation of preexisting conditions are important and largely unanswered
      questions. For BMT survivors, screening recommendations must incorporate risks
      associated with pre-BMT therapy as well as risks related to transplant
      conditioning and graft-versus-host disease. Here, we describe our approach to
      monitoring BMT survivors for risk-based screening and early detection of key late
      occurring or long-term complications using patient scenarios to illustrate our
      discussion.

PMID- 28743717
TI  - Analysis of the recovery of CD247 expression in a PID patient: insights into the
      spontaneous repair of defective genes.
AB  - Mutations in T-cell antigen receptor (TCR) subunit genes cause rare
      immunodeficiency diseases characterized by impaired expression of the TCR at the
      cell surface and selective T lymphopenia. Here, detailed analyses of
      spontaneously arising somatic mutations that recover CD247, and thus TCR
      expression, in a newly identified CD247-deficient patient are described. The
      recovery of CD247 expression in some patient T cells was associated with both
      reversion of the inactivating mutation and a variant with a compensating mutation
      that could reconstitute TCR expression, but not as efficiently as wild-type
      CD247. Multiple mutations were found in CD247 complementary DNAs (cDNAs) cloned
      from the patient as well as in cDNA and genomic DNA from other individuals,
      suggesting that genetic variation in this gene is frequent. Analyses of other
      genes mutated in primary immunodeficiency diseases (PIDs) where reversions have
      been described also revealed a higher rate of mutation than that observed for
      genes mutated in PIDs where revertants have not been identified or control genes.
      These data support the hypothesis that the occurrence of somatic mutations that
      may reconstitute genetic defects in PID is related to an increased propensity of
      those genes to mutate.

PMID- 28743718
TI  - Twinfilin 2a regulates platelet reactivity and turnover in mice.
AB  - Regulated reorganization of the actin cytoskeleton is a prerequisite for proper
      platelet production and function. Consequently, defects in proteins controlling
      actin dynamics have been associated with platelet disorders in humans and mice.
      Twinfilin 2a (Twf2a) is a small actin-binding protein that inhibits actin
      filament assembly by sequestering actin monomers and capping filament barbed
      ends. Moreover, Twf2a binds heterodimeric capping proteins, but the role of this
      interaction in cytoskeletal dynamics has remained elusive. Even though Twf2a has
      pronounced effects on actin dynamics in vitro, only little is known about its
      function in vivo. Here, we report that constitutive Twf2a-deficient mice (Twf2a-/
      ) display mild macrothrombocytopenia due to a markedly accelerated platelet
      clearance in the spleen. Twf2a-/- platelets showed enhanced integrin activation
      and alpha-granule release in response to stimulation of (hem) immunoreceptor
      tyrosine-based activation motif (ITAM) and G-protein-coupled receptors, increased
      adhesion and aggregate formation on collagen I under flow, and accelerated clot
      retraction and spreading on fibrinogen. In vivo, Twf2a deficiency resulted in
      shortened tail bleeding times and faster occlusive arterial thrombus formation.
      The hyperreactivity of Twf2a-/- platelets was attributed to enhanced actin
      dynamics, characterized by an increased activity of n-cofilin and profilin 1,
      leading to a thickened cortical cytoskeleton and hence sustained integrin
      activation by limiting calpain-mediated integrin inactivation. In summary, our
      results reveal the first in vivo functions of mammalian Twf2a and demonstrate
      that Twf2a-controlled actin rearrangements dampen platelet activation responses
      in a n-cofilin- and profilin 1-dependent manner, thereby indirectly regulating
      platelet reactivity and half-life in mice.

PMID- 28743719
TI  - The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil
      recruitment and tissue damage.
AB  - CCRL2 is a 7-transmembrane domain receptor that shares structural and functional
      similarities with the family of atypical chemokine receptors (ACKRs). CCRL2 is
      upregulated by inflammatory signals and, unlike other ACKRs, it is not a
      chemoattractant-scavenging receptor, does not activate beta-arrestins, and is
      widely expressed by many leukocyte subsets. Therefore, the biological role of
      CCRL2 in immunity is still unclear. We report that CCRL2-deficient mice have a
      defect in neutrophil recruitment and are protected in 2 models of inflammatory
      arthritis. In vitro, CCRL2 was found to constitutively form homodimers and
      heterodimers with CXCR2, a main neutrophil chemotactic receptor. By
      heterodimerization, CCRL2 could regulate membrane expression and promote CXCR2
      functions, including the activation of beta2-integrins. Therefore, upregulation
      of CCRL2 observed under inflammatory conditions is functional to finely tune
      CXCR2-mediated neutrophil recruitment at sites of inflammation.

PMID- 28743720
TI  - Doctors urge Britain to take lead on nuclear disarmament.

PMID- 28743721
TI  - MinD directly interacting with FtsZ at the H10 helix suggests a model for robust
      activation of MinC to destabilize FtsZ polymers.
AB  - Cell division in bacteria is a highly controlled and regulated process. FtsZ, a
      bacterial cytoskeletal protein, forms a ring-like structure known as the Z-ring
      and recruits more than a dozen other cell division proteins. The Min system
      oscillates between the poles and inhibits the Z-ring formation at the poles by
      perturbing FtsZ assembly. This leads to an increase in the FtsZ concentration at
      the mid-cell and helps in Z-ring positioning. MinC, the effector protein,
      interferes with Z-ring formation through two different mechanisms mediated by its
      two domains with the help of MinD. However, the mechanism by which MinD triggers
      MinC activity is not yet known. We showed that MinD directly interacts with FtsZ
      with an affinity stronger than the reported MinC-FtsZ interaction. We determined
      the MinD-binding site of FtsZ using computational, mutational and biochemical
      analyses. Our study showed that MinD binds to the H10 helix of FtsZ. Single-point
      mutations at the charged residues in the H10 helix resulted in a decrease in the
      FtsZ affinity towards MinD. Based on our findings, we propose a novel model for
      MinCD-FtsZ interaction, where MinD through its direct interaction with FtsZ would
      trigger MinC activity to inhibit FtsZ functions.

PMID- 28743722
TI  - Bedside Tracheostomy on Pediatric ICU Subjects Supported by Extracorporeal
      Membrane Oxygenation.
AB  - BACKGROUND: Tracheostomy facilitates ambulatory extracorporeal membrane
      oxygenation (ECMO) as a bridge to recovery or lung transplantation in patients
      with respiratory failure, yet data on this procedure in this population are
      lacking. This report describes a series of pediatric ICU patients who had a
      bedside tracheostomy performed while being supported on ECMO and examines the
      potential impact of this procedure on active rehabilitation and sedation
      requirements. METHODS: This retrospective case series reviews all patients in the
      pediatric ICU who received a tracheostomy while being supported on ECMO at a
      single tertiary care center for the past 3 y. This descriptive report reviews the
      surgical procedure, anticoagulation management, adjustments to sedation, and
      complications. RESULTS: Nine subjects between January 2013 and December 2015 were
      identified for review. The subjects ranged in age from 7 y to 25 y. All
      tracheostomies were performed as bedside procedures in the pediatric ICU. All
      subjects but one were supported by venovenous ECMO. Surgical approaches included
      open tracheostomy (2 subjects, 22%), percutaneous tracheostomy (1 subject, 11%),
      and a hybrid approach (6 subjects, 67%). Anticoagulation was held for all
      subjects surrounding the procedure. Three subjects had superficial bleeding after
      the procedure, but only one required re-exploration of the surgical field. All
      subjects made substantial sedation weans within 72 h of tracheostomy. With these
      weans, subjects were better able to participate in rehabilitation. Five subjects
      (55.6%) ambulated on ECMO. The rate of survival to hospital discharge was 67%,
      and no deaths were related to the tracheostomy procedure. CONCLUSIONS: Bedside
      tracheostomy can feasibly be performed on pediatric patients being supported with
      ECMO as a way to improve mobility, promote ambulation, and decrease sedation.
      Timing and ideal surgical approach require further study to fully maximize
      benefits and minimize risks.

PMID- 28743723
TI  - Child treated for HIV in infancy has been healthy for nine years.

PMID- 28743724
TI  - Changes in White Matter Microstructure Impact Cognition by Disrupting the Ability
      of Neural Assemblies to Synchronize.
AB  - Cognition is compromised by white matter (WM) injury but the neurophysiological
      alterations linking them remain unclear. We hypothesized that reduced neural
      synchronization caused by disruption of neural signal propagation is involved. To
      test this, we evaluated group differences in: diffusion tensor WM microstructure
      measures within the optic radiations, primary visual area (V1), and cuneus;
      neural phase synchrony to a visual attention cue during visual-motor task; and
      reaction time to a response cue during the same task between 26 pediatric
      patients (17/9: male/female) treated with cranial radiation treatment for a brain
      tumor (12.67 +/- 2.76 years), and 26 healthy children (16/10: male/female; 12.01
      +/- 3.9 years). We corroborated our findings using a corticocortical
      computational model representing perturbed signal conduction from myelin.
      Patients show delayed reaction time, WM compromise, and reduced phase synchrony
      during visual attention compared with healthy children. Notably, using partial
      least-squares-path modeling we found that WM insult within the optic radiations,
      V1, and cuneus is a strong predictor of the slower reaction times via disruption
      of neural synchrony in visual cortex. Observed changes in synchronization were
      reproduced in a computational model of WM injury. These findings provide new
      evidence linking cognition with WM via the reliance of neural synchronization on
      propagation of neural signals.SIGNIFICANCE STATEMENT By comparing brain tumor
      patients to healthy children, we establish that changes in the microstructure of
      the optic radiations and neural synchrony during visual attention predict
      reaction time. Furthermore, by testing the directionality of these links through
      statistical modeling and verifying our findings with computational modeling, we
      infer a causal relationship, namely that changes in white matter microstructure
      impact cognition in part by disturbing the ability of neural assemblies to
      synchronize. Together, our human imaging data and computer simulations show a
      fundamental connection between WM microstructure and neural synchronization that
      is critical for cognitive processing.

PMID- 28743725
TI  - Altered Balance of Receptive Field Excitation and Suppression in Visual Cortex of
      Amblyopic Macaque Monkeys.
AB  - In amblyopia, a visual disorder caused by abnormal visual experience during
      development, the amblyopic eye (AE) loses visual sensitivity whereas the fellow
      eye (FE) is largely unaffected. Binocular vision in amblyopes is often disrupted
      by interocular suppression. We used 96-electrode arrays to record neurons and
      neuronal groups in areas V1 and V2 of six female macaque monkeys (Macaca
      nemestrina) made amblyopic by artificial strabismus or anisometropia in early
      life, as well as two visually normal female controls. To measure suppressive
      binocular interactions directly, we recorded neuronal responses to dichoptic
      stimulation. We stimulated both eyes simultaneously with large sinusoidal
      gratings, controlling their contrast independently with raised-cosine modulators
      of different orientations and spatial frequencies. We modeled each eye's
      receptive field at each cortical site using a difference of Gaussian envelopes
      and derived estimates of the strength of central excitation and surround
      suppression. We used these estimates to calculate ocular dominance separately for
      excitation and suppression. Excitatory drive from the FE dominated amblyopic
      visual cortex, especially in more severe amblyopes, but suppression from both the
      FE and AEs was prevalent in all animals. This imbalance created strong
      interocular suppression in deep amblyopes: increasing contrast in the AE
      decreased responses at binocular cortical sites. These response patterns reveal
      mechanisms that likely contribute to the interocular suppression that disrupts
      vision in amblyopes.SIGNIFICANCE STATEMENT Amblyopia is a developmental visual
      disorder that alters both monocular vision and binocular interaction. Using
      microelectrode arrays, we examined binocular interaction in primary visual cortex
      and V2 of six amblyopic macaque monkeys (Macaca nemestrina) and two visually
      normal controls. By stimulating the eyes dichoptically, we showed that, in
      amblyopic cortex, the binocular combination of signals is altered. The excitatory
      influence of the two eyes is imbalanced to a degree that can be predicted from
      the severity of amblyopia, whereas suppression from both eyes is prevalent in all
      animals. This altered balance of excitation and suppression reflects mechanisms
      that may contribute to the interocular perceptual suppression that disrupts
      vision in amblyopes.

PMID- 28743726
TI  - Why New Spinal Cord Plasticity Does Not Disrupt Old Motor Behaviors.
AB  - When new motor learning changes the spinal cord, old behaviors are not impaired;
      their key features are preserved by additional compensatory plasticity. To
      explore the mechanisms responsible for this compensatory plasticity, we
      transected the spinal dorsal ascending tract before or after female rats acquired
      a new behavior-operantly conditioned increase or decrease in the right soleus H
      reflex-and examined an old behavior-locomotion. Neither spinal dorsal ascending
      tract transection nor H-reflex conditioning alone impaired locomotion.
      Nevertheless, when spinal dorsal ascending tract transection and H-reflex
      conditioning were combined, the rats developed a limp and a tilted posture that
      correlated in direction and magnitude with the H-reflex change. When the right H
      reflex was increased by conditioning, the right step lasted longer than the left
      and the right hip was higher than the left; when the right H-reflex was decreased
      by conditioning, the opposite occurred. These results indicate that ascending
      sensory input guides the compensatory plasticity that normally prevents the
      plasticity underlying H-reflex change from impairing locomotion. They support the
      concept of the state of the spinal cord as a negotiated equilibrium that reflects
      the concurrent influences of all the behaviors in an individual's repertoire; and
      they support the new therapeutic strategies this concept introduces.SIGNIFICANCE
      STATEMENT The spinal cord provides a reliable final common pathway for motor
      behaviors throughout life. Until recently, its reliability was explained by the
      assumption that it is hardwired; but it is now clear that the spinal cord changes
      continually as new behaviors are acquired. Nevertheless, old behaviors are
      preserved. This study shows that their preservation depends on sensory feedback
      from the spinal cord to the brain: if feedback is removed, the acquisition of a
      new behavior may disrupt an old behavior. In sum, when a new behavior changes the
      spinal cord, sensory feedback to the brain guides further change that preserves
      old behaviors. This finding contributes to a new understanding of spinal cord
      function and to development of new rehabilitation therapies.

PMID- 28743728
TI  - Imaging regiospecific lipid turnover in mouse brain with desorption electrospray
      ionization mass spectrometry.
AB  - Compartmentalization of metabolism into specific regions of the cell, tissue, and
      organ is critical to life for all organisms. Mass spectrometric imaging
      techniques have been valuable in identifying and quantifying concentrations of
      metabolites in specific locations of cells and tissues, but a true understanding
      of metabolism requires measurement of metabolite flux on a spatially resolved
      basis. Here, we utilize desorption ESI-MS (DESI-MS) to measure lipid turnover in
      the brains of mice. We show that anatomically distinct regions of the brain have
      distinct lipid turnover rates. These turnover measurements, in conjunction with
      relative concentration, will enable calculation of regiospecific synthesis rates
      for individual lipid species in vivo. Monitoring spatially dependent changes in
      metabolism has the potential to significantly facilitate research in many areas,
      such as brain development, cancer, and neurodegeneration.

PMID- 28743727
TI  - Basolateral Amygdala to Orbitofrontal Cortex Projections Enable Cue-Triggered
      Reward Expectations.
AB  - To make an appropriate decision, one must anticipate potential future rewarding
      events, even when they are not readily observable. These expectations are
      generated by using observable information (e.g., stimuli or available actions) to
      retrieve often quite detailed memories of available rewards. The basolateral
      amygdala (BLA) and orbitofrontal cortex (OFC) are two reciprocally connected key
      nodes in the circuitry supporting such outcome-guided behaviors. But there is
      much unknown about the contribution of this circuit to decision making, and
      almost nothing known about the whether any contribution is via direct,
      monosynaptic projections, or the direction of information transfer. Therefore,
      here we used designer receptor-mediated inactivation of OFC->BLA or BLA->OFC
      projections to evaluate their respective contributions to outcome-guided
      behaviors in rats. Inactivation of BLA terminals in the OFC, but not OFC
      terminals in the BLA, disrupted the selective motivating influence of cue
      triggered reward representations over reward-seeking decisions as assayed by
      Pavlovian-to-instrumental transfer. BLA->OFC projections were also required when
      a cued reward representation was used to modify Pavlovian conditional goal
      approach responses according to the reward's current value. These projections
      were not necessary when actions were guided by reward expectations generated
      based on learned action-reward contingencies, or when rewards themselves, rather
      than stored memories, directed action. These data demonstrate that BLA->OFC
      projections enable the cue-triggered reward expectations that can motivate the
      execution of specific action plans and allow adaptive conditional
      responding.SIGNIFICANCE STATEMENT Deficits anticipating potential future
      rewarding events are associated with many psychiatric diseases. Presently, we
      know little about the neural circuits supporting such reward expectation. Here we
      show that basolateral amygdala to orbitofrontal cortex projections are required
      for expectations of specific available rewards to influence reward seeking and
      decision making. The necessity of these projections was limited to situations in
      which expectations were elicited by reward-predictive cues. These projections
      therefore facilitate adaptive behavior by enabling the orbitofrontal cortex to
      use environmental stimuli to generate expectations of potential future rewarding
      events.

PMID- 28743729
TI  - Obesity is associated with an altered HDL subspecies profile among adolescents
      with metabolic disease.
AB  - We aimed to determine the risk factors associated with the depletion of large HDL
      particles and enrichment of small HDL particles observed in adolescents with T2D.
      Four groups of adolescents were recruited: 1) lean insulin-sensitive (L-IS),
      normal BMI and no insulin resistance; 2) lean insulin-resistant (L-IR), normal
      BMI but insulin resistance (fasting insulin levels >= 25 mU/ml and homeostatic
      model assessment of insulin resistance >= 6); 3) obese insulin-sensitive (O-IS),
      BMI >= 95th percentile and no insulin resistance; and 4) obese insulin-resistant
      (O-IR), BMI >= 95th percentile and insulin resistance. Plasma was separated by
      using gel-filtration chromatography to assess the HDL subspecies profile and
      compared with that of obese adolescents with T2D (O-T2D). Large HDL subspecies
      were significantly lower across groups from L-IS > L-IR > O-IS > O-IR > O-T2D (P
      < 0.0001); small HDL particles were higher from L-IS to O-T2D (P < 0.0001); and
      medium-sized particles did not differ across groups. The contributions of
      obesity, insulin resistance, and diabetes to HDL subspecies profile were between
      23% and 28%, 1% and 10%, and 4% and 9%, respectively. Obesity is the major risk
      factor associated with the altered HDL subspecies profile previously reported in
      adolescents with T2D, with smaller contributions from insulin resistance and
      diabetes.

PMID- 28743730
TI  - Do cardiometabolic, behavioural and socioeconomic factors explain the 'healthy
      migrant effect' in the UK? Linked mortality follow-up of South Asians compared
      with white Europeans in the Newcastle Heart Project.
AB  - BACKGROUND: Immigrants are sometimes found to have better health than locally
      born populations. We examined the mortality experience of South Asian origin and
      white European origin individuals living in Newcastle upon Tyne, UK. METHODS: A
      linked 17-21 year mortality follow-up of a cross-sectional study of European
      (n=825) and South Asian (n=709) men and women, aged 25-74 years, recruited
      between 1993 and 1997. Poisson regression was used to estimate mortality rate
      ratios (MRRs) for all-cause mortality. Sensitivity analysis explored the possible
      effect of differences between ethnic groups in loss to follow-up. The impact of
      adjustment for established risk factors on MRRs was studied. RESULTS: South
      Asians had lower all-cause age-adjusted and sex-adjusted mortality than Europeans
      (MRR 0.70; 95% CI 0.58 to 0.85). There was higher loss to follow-up in South
      Asians. Sensitivity analyses demonstrated that this did not account for the
      observed lower mortality. Adjustment for cardiometabolic, behavioural and
      socioeconomic characteristics attenuated but did not eliminate the mortality
      differences between South Asians and Europeans, although CIs now cross 1 (MRR
      0.79; 95% CI 0.55 to 1.13). CONCLUSIONS: South Asians had lower all-cause
      mortality compared with European origin individuals living in Newcastle upon Tyne
      that were not accounted for by incomplete mortality data. It is possible that
      such migrants to the UK have the resources and motivation to move in search of
      better opportunities and may be healthier and wealthier than those who remain in
      their country of origin. These findings challenge us to better understand and
      measure the factors contributing to their survival advantage.

PMID- 28743731
TI  - Shifting disease burden in low and middle-income countries: a 14-year survival
      analysis of childhood mortality in Bangladesh.
AB  - BACKGROUND: The objective of this study is to compare all-cause mortality and
      drowning-specific mortality rates and survival times among birth cohorts of
      children from rural Bangladesh over a 14-year period. METHOD: Seven birth cohorts
      of children aged 12-59 months were created using data from the Matlab Health and
      Demographic Surveillance System in Bangladesh. Each cohort represents children
      born within a 2-year interval between 1 July 1995 and 30 June 2009, who were then
      evaluated over a 2-year snapshot. All-cause and drowning-specific mortality rates
      were compared for each cohort using the oldest cohort (cohort 1) as reference. A
      Cox proportional model was used to estimate hazard rate ratios (HRR) comparing
      the cohorts, and adjusted for key independent variables. Kaplan-Meier survivor
      function was estimated for each birth cohort and compared with cohort 1 using log
      rank test. RESULTS: The adjusted HRR for all-cause mortality showed that children
      in cohorts 4, 5, 6 and 7 had significantly lower hazard rate compared with cohort
      1 with a dose-response relationship, the adjusted HRRs were 0.51 (95% CI 0.31,
      0.84), 0.53 (95% CI 0.32, 0.87), 0.44 (95% CI 0.26, 0.76) and 0.42 (95% CI 0.24,
      0.74), respectively. For drowning, none of the adjusted HRR was statistically
      significant. Mother's primary education and being married were protective of risk
      of death from all causes. CONCLUSION: Whereas child mortality rates from all
      causes declined remarkably between 1998 and 2012 in rural Bangladesh, drowning
      specific mortality rates remained unchanged. This shifting burden of disease
      underscores the epidemiological transition in the childhood causes of death in
      Bangladesh and the need for urgent action to review child health interventions.

PMID- 28743732
TI  - Introduction of allergenic foods from 3 months of age reduces incidence of food
      allergy in breastfed infants.

PMID- 28743733
TI  - Paediatric inflammatory bowel disease: a presenting lesion.

PMID- 28743735
TI  - LILRB4 deficiency aggravates the development of atherosclerosis and plaque
      instability by increasing the macrophage inflammatory response via NF-kappaB
      signaling.
AB  - Atherosclerosis is a chronic inflammatory disease. LILRB4 is associated with the
      pathological processes of various inflammatory diseases. However, the potential
      function and underlying mechanisms of LILRB4 in atherogenesis remain to be
      investigated. In this study, LILRB4 expression was examined in both human and
      mouse atherosclerotic plaques. The effects and possible mechanisms of LILRB4 in
      atherogenesis and plaque instability were evaluated in LILRB4-/-ApoE-/- and ApoE
      /- mice fed a high-fat diet. We found that LILRB4 was located primarily in
      macrophages, and its expression was up-regulated in atherosclerotic lesions from
      human coronary arteries and mouse aortic roots. LILRB4 deficiency significantly
      accelerated the development of atherosclerotic lesions and increased the
      instability of plaques, as evidenced by the increased infiltration of lipids,
      decreased amount of collagen components and smooth muscle cells. Moreover, LILRB4
      deficiency in bone marrow-derived cells promoted the development of
      atherosclerosis. In vivo and in vitro analyses revealed that the pro-inflammatory
      effects of LILRB4 deficiency were mediated by the increased activation of NF
      kappaB signaling due to decreased Shp1 phosphorylation. In conclusion, the
      present study indicates that LILRB4 deficiency promotes atherogenesis, at least
      partly, through reduced Shp1 phosphorylation, which subsequently enhances the NF
      kappaB-mediated inflammatory response. Thus, targeting the "LILRB4-Shp1" axis may
      be a novel therapeutic approach for atherosclerosis.

PMID- 28743734
TI  - Centriole translocation and degeneration during ciliogenesis in Caenorhabditis
      elegans neurons.
AB  - Neuronal cilia that are formed at the dendritic endings of sensory neurons are
      essential for sensory perception. However, it remains unclear how the centriole
      derived basal body is positioned to form a template for cilium formation. Using
      fluorescence time-lapse microscopy, we show that the centriole translocates from
      the cell body to the dendrite tip in the Caenorhabditis elegans sensory neurons.
      The centriolar protein SAS-5 interacts with the dynein light-chain LC8 and
      conditional mutations of cytoplasmic dynein-1 block centriole translocation and
      ciliogenesis. The components of the central tube are essential for the biogenesis
      of centrioles, which later drive ciliogenesis in the dendrite; however, the
      centriole loses these components at the late stage of centriole translocation and
      subsequently recruits transition zone and intraflagellar transport proteins.
      Together, our results provide a comprehensive model of ciliogenesis in sensory
      neurons and reveal the importance of the dynein-dependent centriole translocation
      in this process.

PMID- 28743736
TI  - SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A.
AB  - Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide
      phosphodiesterase (PDE) family, plays important roles in oocyte maturation and
      vascular smooth muscle cell proliferation. However, the molecular mechanisms that
      regulate PDE3A gene expression remain largely unknown. In this study, we
      investigated the transcriptional regulation of PDE3A , and found that the
      splicing factor proline and glutamine rich (SFPQ) protein modulated PDE3A mRNA
      levels. Multiple transcription start sites (TSS1, 2, and 3) were identified
      within the first exon of PDE3A using 5'-rapid amplification of cDNA ends (RACE).
      Variable expression levels of three PDE3A variants were also observed in human
      tissues and HeLa cells. Several putative SFPQ-binding sites were identified
      upstream of the regulatory region of PDE3A -TSSs using chromatin
      immunoprecipitation sequencing (ChIP-seq). Serum-induced PDE3A expression was
      affected by increasing the amount of SFPQ binding to the upstream regulatory
      region of PDE3A In addition, transcription of PDE3A was lower in human cervical
      adenocarcinoma cells compared to normal cervical tissue. Furthermore, over
      expression of PDE3A induced sensitivity to anti-cancer therapeutic agent, 6-(4
      (diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (DNMDP), in
      HeLa cells. Taken together, these results suggest that SFPQ functions as a
      transcriptional activator of PDE3A, which is involved in the regulation of DNMDP
      sensitivity , offering a novel molecular target for the development of anticancer
      therapies.

PMID- 28743737
TI  - Real-time visualization of chromatin modification in isolated nuclei.
AB  - Chromatin modification is traditionally assessed in biochemical assays that
      provide average measurements of static events given that the analysis requires
      components from many cells. Microscopy can visualize single cells, but the cell
      body and organelles can hamper staining and visualization of the nucleus.
      Normally, chromatin is visualized by immunostaining a fixed sample or by
      expressing exogenous fluorescently tagged proteins in a live cell. Alternative
      microscopy tools to observe changes of endogenous chromatin in real-time are
      needed. Here, we isolated transcriptionally competent nuclei from cells and used
      antibody staining without fixation to visualize changes in endogenous chromatin.
      This method allows the real-time addition of drugs and fluorescent probes to one
      or more nuclei while under microscopy observation. A high-resolution map of 11
      endogenous nuclear markers of the histone code, transcription machinery and
      architecture was obtained in transcriptionally active nuclei by performing
      confocal and structured illumination microscopy. We detected changes in chromatin
      modification and localization at the single-nucleus level after inhibition of
      histone deacetylation. Applications in the study of RNA transcription, viral
      protein function and nuclear architecture are presented. This article has an
      associated First Person interview with the first author of the paper.

PMID- 28743738
TI  - Premature termination codon readthrough in human cells occurs in novel
      cytoplasmic foci and requires UPF proteins.
AB  - Nonsense-mutation-containing messenger ribonucleoprotein particles (mRNPs)
      transit through cytoplasmic foci called P-bodies before undergoing nonsense
      mediated mRNA decay (NMD), a cytoplasmic mRNA surveillance mechanism. This study
      shows that the cytoskeleton modulates transport of nonsense-mutation-containing
      mRNPs to and from P-bodies. Impairing the integrity of cytoskeleton causes
      inhibition of NMD. The cytoskeleton thus plays a crucial role in NMD.
      Interestingly, disruption of actin filaments results in both inhibition of NMD
      and activation of premature termination codon (PTC) readthrough, while disruption
      of microtubules causes only NMD inhibition. Activation of PTC readthrough occurs
      concomitantly with the appearance of cytoplasmic foci containing UPF proteins and
      mRNAs with nonsense mutations but lacking the P-body marker DCP1a. These findings
      demonstrate that in human cells, PTC readthrough occurs in novel 'readthrough
      bodies' and requires the presence of UPF proteins.

PMID- 28743739
TI  - IP6K1 is essential for chromatoid body formation and temporal regulation of Tnp2
      and Prm2 expression in mouse spermatids.
AB  - Inositol hexakisphosphate kinases (IP6Ks) are enzymes that synthesise the
      inositol pyrophosphate 5-diphosphoinositol pentakisphosphate (5-IP7), which is
      known to regulate several physiological processes. Deletion of IP6K1, but not
      other IP6K isoforms, causes sterility in male mice. Here, we present a detailed
      investigation of the specific function of IP6K1 in spermatogenesis. Within the
      mouse testis, IP6K1 is expressed at high levels in late stage pachytene
      spermatocytes and in round spermatids. We found IP6K1 to be a novel component of
      the chromatoid body, a cytoplasmic granule found in round spermatids that is
      composed of RNA and RNA-binding proteins, and noted that this structure is absent
      in Ip6k1-/- round spermatids. Furthermore, juvenile spermatids from Ip6k1-/- mice
      display premature expression of the transition protein TNP2 and the protamine
      PRM2 due to translational derepression. The aberrant localisation of these key
      sperm-specific chromatin components, together with the persistence of somatic
      histones, results in abnormal spermatid elongation, failure to complete spermatid
      differentiation and azoospermia in these mice. Our study thus identifies IP6K1 as
      an indispensable factor in the temporal regulation of male germ cell
      differentiation.This article has an associated First Person interview with the
      first author of the paper.

PMID- 28743740
TI  - Multiple E2 ubiquitin-conjugating enzymes regulate human cytomegalovirus US2
      mediated immunoreceptor downregulation.
AB  - Misfolded endoplasmic reticulum (ER) proteins are dislocated towards the cytosol
      and degraded by the ubiquitin-proteasome system in a process called ER-associated
      protein degradation (ERAD). During infection with human cytomegalovirus (HCMV),
      the viral US2 protein targets HLA class I molecules (HLA-I) for degradation via
      ERAD to avoid elimination by the immune system. US2-mediated degradation of HLA-I
      serves as a paradigm of ERAD and has facilitated the identification of TRC8 (also
      known as RNF139) as an E3 ubiquitin ligase. No specific E2 enzymes had previously
      been described for cooperation with TRC8. In this study, we used a lentiviral
      CRISPR/Cas9 library targeting all known human E2 enzymes to assess their
      involvement in US2-mediated HLA-I downregulation. We identified multiple E2
      enzymes involved in this process, of which UBE2G2 was crucial for the degradation
      of various immunoreceptors. UBE2J2, on the other hand, counteracted US2-induced
      ERAD by downregulating TRC8 expression. These findings indicate the complexity of
      cellular quality control mechanisms, which are elegantly exploited by HCMV to
      elude the immune system.

PMID- 28743741
TI  - CDK9 and SPT5 proteins are specifically required for expression of herpes simplex
      virus 1 replication-dependent late genes.
AB  - DNA replication greatly enhances expression of the herpes simplex virus 1 (HSV-1)
      gamma2 late genes by still unknown mechanisms. Here, we demonstrate that 5,6
      dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB), an inhibitor of CDK9,
      suppresses expression of gamma2 late genes with an IC50 of 5 MUm, which is at
      least 10 times lower than the IC50 value required for inhibition of expression of
      early genes. The effect of DRB could not be explained by inhibition of DNA
      replication per se or loading of RNA polymerase II to late promoters and
      subsequent reduction of transcription. Instead, DRB reduces accumulation of
      gamma2 late mRNA in the cytoplasm. In addition, we show that siRNA-mediated
      knockdown of the transcription factor SPT5, but not NELF-E, also gives rise to a
      specific inhibition of HSV-1 late gene expression. Finally, addition of DRB
      reduces co-immunoprecipitation of ICP27 using an anti-SPT5 antibody. Our results
      suggest that efficient expression of replication-dependent gamma2 late genes is,
      at least in part, regulated by CDK9 dependent co- and/or post-transcriptional
      events involving SPT5 and ICP27.

PMID- 28743742
TI  - Disease-causing mutations in the serpin antithrombin reveal a key domain critical
      for inhibiting protease activities.
AB  - Antithrombin mainly inhibits factor Xa and thrombin. The reactive center loop
      (RCL) is crucial for its interactions with its protease targets and is fully
      inserted into the A-sheet after its cleavage, causing translocation of the
      covalently linked protease to the opposite end of the A-sheet. Antithrombin
      variants with altered RCL hinge residues behave as substrates rather than
      inhibitors, resulting in stoichiometries of inhibition greater than one. Other
      antithrombin residues have been suggested to interfere with RCL insertion or the
      stability of the antithrombin-protease complex, but available crystal structures
      or mutagenesis studies have failed to identify such residues. Here, we
      characterized two mutations, S365L and I207T, present in individuals with type II
      antithrombin deficiency and identified a new antithrombin functional domain.
      S365L did not form stable complexes with thrombin or factor Xa, and the
      I207T/I207A variants inhibited both proteases with elevated stoichiometries of
      inhibition. Close proximity of Ile-207 and Ser-365 to the inserted RCL suggested
      that the preferred reaction of these mutants as protease substrates reflects an
      effect on the rate of the RCL insertion and protease translocation. However, both
      residues lie within the final docking site for the protease in the antithrombin
      protease complex, supporting the idea that the enhanced substrate reactions may
      result from an increased dissociation of the final complexes. Our findings
      demonstrate that the distal end of the antithrombin A-sheet is crucial for the
      last steps of protease inhibition either by affecting the rate of RCL insertion
      or through critical interactions with proteases at the end of the A-sheet.

PMID- 28743743
TI  - Characterization of a stable HIV-1 B/C recombinant, soluble, and trimeric
      envelope glycoprotein (Env) highly resistant to CD4-induced conformational
      changes.
AB  - The HIV-1 envelope (Env) is a glycoprotein consisting of a trimer of heterodimers
      containing gp120 and gp41 subunits that mediates virus entry and is a major
      target of broadly neutralizing antibodies (bnAbs) developed during infection in
      some individuals. The engagement of the HIV-1 gp120 glycoprotein to the host CD4
      protein triggers conformational changes in gp120 that allow its binding to co
      receptors and is necessary for virus entry to establish infection. Native-like
      HIV-1 Env immunogens representing distinct clades have been proposed to improve
      immunogenicity. In the present study, we examined the basis of resistance of an
      HIV-1 B/C recombinant Env (LT5.J4b12C) to non-neutralizing antibodies targeting
      CD4-induced Env epitopes in the presence of soluble CD4 (sCD4). Using native
      polyacrylamide gel shift assay and negative-stain EM, we found that the prefusion
      conformational state of LT5.J4b12C trimeric Env was largely unaffected in the
      presence of excess sCD4 with most Env trimers appearing to be in a ligand-free
      state. This resistance to CD4-induced conformational changes was associated with
      a lower affinity for CD4. Moreover, the LT5.J4b12C trimeric Env preferentially
      bound to the neutralizing antibodies compared with non-neutralizing antibodies.
      Taken together, we report on an HIV-1 B/C recombinant, native-like trimeric Env
      protein that is highly resistant to CD4-induced conformational changes but
      displays epitopes recognized by a diverse array of bnAbs. Such features make this
      B/C recombinant trimeric Env a useful addition to the pool of other recently
      identified native-like HIV-1 Env trimers suitable for use as antigenic bait for
      bnAb isolation, structural studies, and use as potential immunogens.

PMID- 28743744
TI  - Phosphatidylinositol 3,5-bisphosphate is involved in methylglyoxal-induced
      activation of the Mpk1 mitogen-activated protein kinase cascade in Saccharomyces
      cerevisiae.
AB  - Methylglyoxal (MG) is a natural metabolite derived from glycolysis, and this 2
      oxoaldehyde has been implicated in some diseases including diabetes. However, the
      physiological significance of MG for cellular functions is yet to be fully
      elucidated. We previously reported that MG activates the Mpk1 (MAPK) cascade in
      the yeast Saccharomyces cerevisiae To gain further insights into the cellular
      functions and responses to MG, we herein screened yeast-deletion mutant
      collections for susceptibility to MG. We found that mutants defective in the
      synthesis of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) are more
      susceptible to MG. PtdIns(3,5)P2 levels increased following MG treatment, and
      vacuolar morphology concomitantly changed to a single swollen shape. MG activated
      the Pkc1-Mpk1 MAPK cascade in which a small GTPase Rho1 plays a crucial role, and
      the MG-induced phosphorylation of Mpk1 was impaired in mutants defective in the
      PtdIns(3,5)P2 biosynthetic pathway. Of note, heat shock-induced stress also
      provoked Mpk1 phosphorylation in a Rho1-dependent manner; however, PtdIns(3,5)P2
      was dispensable for the heat shock-stimulated activation of this signaling
      pathway. Our results suggest that PtdIns(3,5)P2 is specifically involved in the
      MG-induced activation of the Mpk1 MAPK cascade and in the cellular adaptation to
      MG-induced stress.

PMID- 28743745
TI  - R213I mutation in release factor 2 (RF2) is one step forward for engineering an
      omnipotent release factor in bacteria Escherichia coli.
AB  - The current understanding of the specificity of the bacterial class I release
      factors (RFs) in decoding stop codons has evolved beyond a simple tripeptide
      anticodon model. A recent molecular dynamics study for deciphering the principles
      for specific stop codon recognition by RFs identified Arg-213 as a crucial
      residue on Escherichia coli RF2 for discriminating guanine in the third position
      (G3). Interestingly, Arg-213 is highly conserved in RF2 and substituted by Ile
      196 in the corresponding position in RF1. Another similar pair is Leu-126 in RF1
      and Asp-143 in RF2, which are also conserved within their respective groups. With
      the hypothesis that replacement of Arg-213 and Asp-143 with the corresponding RF1
      residues will reduce G3 discrimination by RF2, we swapped these residues between
      E. coli RF1 and RF2 by site-directed mutagenesis and characterized their
      preference for different codons using a competitive peptide release assay. Among
      these, the R213I mutant of RF2 showed 5-fold improved reading of the RF1-specific
      UAG codon relative to UAA, the universal stop codon, compared with the wild type
      (WT). In-depth fast kinetic studies revealed that the gain in UAG reading by RF2
      R213I is associated with a reduced efficiency of termination on the cognate UAA
      codon. Our work highlights the notion that stop codon recognition involves
      complex interactions with multiple residues beyond the PXT/SPF motifs. We propose
      that the R213I mutation in RF2 brings us one step forward toward engineering an
      omnipotent RF in bacteria, capable of reading all three stop codons.

PMID- 28743746
TI  - De novo triiodothyronine formation from thyrocytes activated by thyroid
      stimulating hormone.
AB  - The thyroid gland secretes primarily tetraiodothyronine (T4), and some
      triiodothyronine (T3). Under normal physiological circumstances, only one-fifth
      of circulating T3 is directly released by the thyroid, but in states of
      hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients
      develop a syndrome of relative T3 toxicosis. Thyroidal T4 production results from
      iodination of thyroglobulin (TG) at residues Tyr5 and Tyr130, whereas thyroidal
      T3 production may originate in several different ways. In this study, the data
      demonstrate that within the carboxyl-terminal portion of mouse TG, T3 is formed
      de novo independently of deiodination from T4 We found that upon iodination in
      vitro, de novo T3 formation in TG was decreased in mice lacking TSHRs.
      Conversely, de novo T3 that can be formed upon iodination of TG secreted from
      PCCL3 (rat thyrocyte) cells was augmented from cells previously exposed to
      increased TSH, a TSHR agonist, a cAMP analog, or a TSHR-stimulating antibody. We
      present data suggesting that TSH-stimulated TG phosphorylation contributes to
      enhanced de novo T3 formation. These effects were reversed within a few days
      after removal of the hyperstimulating conditions. Indeed, direct exposure of
      PCCL3 cells to human serum from two patients with Graves' disease, but not
      control sera, led to secretion of TG with an increased intrinsic ability to form
      T3 upon in vitro iodination. Furthermore, TG secreted from human thyrocyte
      cultures hyperstimulated with TSH also showed an increased intrinsic ability to
      form T3 Our data support the hypothesis that TG processing in the secretory
      pathway of TSHR-hyperstimulated thyrocytes alters the structure of the iodination
      substrate in a way that enhances de novo T3 formation, contributing to the
      relative T3 toxicosis of Graves' disease.

PMID- 28743747
TI  - The UL8 subunit of the helicase-primase complex of herpes simplex virus promotes
      DNA annealing and has a high affinity for replication forks.
AB  - During lytic infection, herpes simplex virus (HSV) DNA is replicated by a
      mechanism involving DNA recombination. For instance, replication of the HSV-1
      genome produces X- and Y-branched structures, reminiscent of recombination
      intermediates. HSV-1's replication machinery includes a trimeric helicase-primase
      composed of helicase (UL5) and primase (UL52) subunits and a third subunit, UL8.
      UL8 has been reported to stimulate the helicase and primase activities of the
      complex in the presence of ICP8, an HSV-1 protein that functions as an annealase,
      a protein that binds complementary single-stranded DNA (ssDNA) and facilitates
      its annealing to duplex DNA. UL8 also influences the intracellular localization
      of the UL5/UL52 subunits, but UL8's catalytic activities are not known. In this
      study we used a combination of biochemical techniques and transmission electron
      microscopy. First, we report that UL8 alone forms protein filaments in solution.
      Moreover, we also found that UL8 binds to ssDNAs >50-nucletides long and promotes
      the annealing of complementary ssDNA to generate highly branched duplex DNA
      structures. Finally, UL8 has a very high affinity for replication fork structures
      containing a gap in the lagging strand as short as 15 nucleotides, suggesting
      that UL8 may aid in directing or loading the trimeric complex onto a replication
      fork. The properties of UL8 uncovered here suggest that UL8 may be involved in
      the generation of the X- and Y-branched structures that are the hallmarks of HSV
      replication.

PMID- 28743748
TI  - Design and synthesis of theranostic antibiotic nanodrugs that display enhanced
      antibacterial activity and luminescence.
AB  - We report the modular formulation of ciprofloxacin-based pure theranostic
      nanodrugs that display enhanced antibacterial activities, as well as aggregation
      induced emission (AIE) enhancement that was successfully used to image bacteria.
      The drug derivatives, consisting of ciprofloxacin, a perfluoroaryl ring, and a
      phenyl ring linked by an amidine bond, were efficiently synthesized by a
      straightforward protocol from a perfluoroaryl azide, ciprofloxacin, and an
      aldehyde in acetone at room temperature. These compounds are propeller-shaped,
      and upon precipitation into water, readily assembled into stable nanoaggregates
      that transformed ciprofloxacin derivatives into AIE-active luminogens. The
      nanoaggregates displayed increased luminescence and were successfully used to
      image bacteria. In addition, these nanodrugs showed enhanced antibacterial
      activities, lowering the minimum inhibitory concentration (MIC) by more than one
      order of magnitude against both sensitive and resistant Escherichia coli The
      study represents a strategy in the design and development of pure theranostic
      nanodrugs for combating drug-resistant bacterial infections.

PMID- 28743749
TI  - SUMOylation determines the voltage required to activate cardiac IKs channels.
AB  - IKs channels open in response to depolarization of the membrane voltage during
      the cardiac action potential, passing potassium ions outward to repolarize
      ventricular myocytes and end each beat. Here, we show that the voltage required
      to activate IKs channels depends on their covalent modification by small
      ubiquitin-like modifier (SUMO) proteins. IKs channels are comprised of four KCNQ1
      pore-forming subunits, two KCNE1 accessory subunits, and up to four SUMOs, one on
      Lys424 of each KCNQ1 subunit. Each SUMO shifts the half-maximal activation
      voltage (V1/2) of IKs ~ +8 mV, producing a maximal +34-mV shift in neonatal mouse
      cardiac myocytes or Chinese hamster ovary (CHO) cells expressing the mouse or
      human subunits. Unexpectedly, channels formed without KCNE1 carry at most two
      SUMOs despite having four available KCNQ1-Lys424 sites. SUMOylation of KCNQ1 is
      KCNE1 dependent and determines the native attributes of cardiac IKs in vivo.

PMID- 28743750
TI  - Serum amyloid A forms stable oligomers that disrupt vesicles at lysosomal pH and
      contribute to the pathogenesis of reactive amyloidosis.
AB  - Serum amyloid A (SAA) is an acute-phase plasma protein that functions in innate
      immunity and lipid homeostasis. SAA is a protein precursor of reactive AA
      amyloidosis, the major complication of chronic inflammation and one of the most
      common human systemic amyloid diseases worldwide. Most circulating SAA is
      protected from proteolysis and misfolding by binding to plasma high-density
      lipoproteins. However, unbound soluble SAA is intrinsically disordered and is
      either rapidly degraded or forms amyloid in a lysosome-initiated process.
      Although acidic pH promotes amyloid fibril formation by this and many other
      proteins, the molecular underpinnings are unclear. We used an array of
      spectroscopic, biochemical, and structural methods to uncover that at pH 3.5-4.5,
      murine SAA1 forms stable soluble oligomers that are maximally folded at pH 4.3
      with ~35% alpha-helix and are unusually resistant to proteolysis. In solution,
      these oligomers neither readily convert into mature fibrils nor bind lipid
      surfaces via their amphipathic alpha-helices in a manner typical of
      apolipoproteins. Rather, these oligomers undergo an alpha-helix to beta-sheet
      conversion catalyzed by lipid vesicles and disrupt these vesicles, suggesting a
      membranolytic potential. Our results provide an explanation for the lysosomal
      origin of AA amyloidosis. They suggest that high structural stability and
      resistance to proteolysis of SAA oligomers at pH 3.5-4.5 help them escape
      lysosomal degradation, promote SAA accumulation in lysosomes, and ultimately
      damage cellular membranes and liberate intracellular amyloid. We posit that these
      soluble prefibrillar oligomers provide a missing link in our understanding of the
      development of AA amyloidosis.

PMID- 28743751
TI  - Nature does not rely on long-lived electronic quantum coherence for
      photosynthetic energy transfer.
AB  - During the first steps of photosynthesis, the energy of impinging solar photons
      is transformed into electronic excitation energy of the light-harvesting
      biomolecular complexes. The subsequent energy transfer to the reaction center is
      commonly rationalized in terms of excitons moving on a grid of biomolecular
      chromophores on typical timescales [Formula: see text]100 fs. Today's
      understanding of the energy transfer includes the fact that the excitons are
      delocalized over a few neighboring sites, but the role of quantum coherence is
      considered as irrelevant for the transfer dynamics because it typically decays
      within a few tens of femtoseconds. This orthodox picture of incoherent energy
      transfer between clusters of a few pigments sharing delocalized excitons has been
      challenged by ultrafast optical spectroscopy experiments with the Fenna-Matthews
      Olson protein, in which interference oscillatory signals up to 1.5 ps were
      reported and interpreted as direct evidence of exceptionally long-lived
      electronic quantum coherence. Here, we show that the optical 2D photon echo
      spectra of this complex at ambient temperature in aqueous solution do not provide
      evidence of any long-lived electronic quantum coherence, but confirm the orthodox
      view of rapidly decaying electronic quantum coherence on a timescale of 60 fs.
      Our results can be considered as generic and give no hint that electronic quantum
      coherence plays any biofunctional role in real photoactive biomolecular
      complexes. Because in this structurally well-defined protein the distances
      between bacteriochlorophylls are comparable to those of other light-harvesting
      complexes, we anticipate that this finding is general and directly applies to
      even larger photoactive biomolecular complexes.

PMID- 28743752
TI  - Thalamocortical synchronization during induction and emergence from propofol
      induced unconsciousness.
AB  - General anesthesia (GA) is a reversible drug-induced state of altered arousal
      required for more than 60,000 surgical procedures each day in the United States
      alone. Sedation and unconsciousness under GA are associated with stereotyped
      electrophysiological oscillations that are thought to reflect profound
      disruptions of activity in neuronal circuits that mediate awareness and
      cognition. Computational models make specific predictions about the role of the
      cortex and thalamus in these oscillations. In this paper, we provide in vivo
      evidence in rats that alpha oscillations (10-15 Hz) induced by the commonly used
      anesthetic drug propofol are synchronized between the thalamus and the medial
      prefrontal cortex. We also show that at deep levels of unconsciousness where
      movement ceases, coherent thalamocortical delta oscillations (1-5 Hz) develop,
      distinct from concurrent slow oscillations (0.1-1 Hz). The structure of these
      oscillations in both cortex and thalamus closely parallel those observed in the
      human electroencephalogram during propofol-induced unconsciousness. During
      emergence from GA, this synchronized activity dissipates in a sequence different
      from that observed during loss of consciousness. A possible explanation is that
      recovery from anesthesia-induced unconsciousness follows a "boot-up" sequence
      actively driven by ascending arousal centers. The involvement of medial
      prefrontal cortex suggests that when these oscillations (alpha, delta, slow) are
      observed in humans, self-awareness and internal consciousness would be impaired
      if not abolished. These studies advance our understanding of anesthesia-induced
      unconsciousness and altered arousal and further establish principled
      neurophysiological markers of these states.

PMID- 28743753
TI  - Spatial gene drives and pushed genetic waves.
AB  - Gene drives have the potential to rapidly replace a harmful wild-type allele with
      a gene drive allele engineered to have desired functionalities. However, an
      accidental or premature release of a gene drive construct to the natural
      environment could damage an ecosystem irreversibly. Thus, it is important to
      understand the spatiotemporal consequences of the super-Mendelian population
      genetics before potential applications. Here, we use a reaction-diffusion model
      for sexually reproducing diploid organisms to study how a locally introduced gene
      drive allele spreads to replace the wild-type allele, although it possesses a
      selective disadvantage s > 0. Using methods developed by Barton and
      collaborators, we show that socially responsible gene drives require 0.5 < s <
      0.697, a rather narrow range. In this "pushed wave" regime, the spatial spreading
      of gene drives will be initiated only when the initial frequency distribution is
      above a threshold profile called "critical propagule," which acts as a safeguard
      against accidental release. We also study how the spatial spread of the pushed
      wave can be stopped by making gene drives uniquely vulnerable ("sensitizing
      drive") in a way that is harmless for a wild-type allele. Finally, we show that
      appropriately sensitized drives in two dimensions can be stopped, even by
      imperfect barriers perforated by a series of gaps.

PMID- 28743754
TI  - SIK3-HDAC4 signaling regulates Drosophila circadian male sex drive rhythm via
      modulating the DN1 clock neurons.
AB  - The physiology and behavior of many organisms are subject to daily cycles. In
      Drosophila melanogaster the daily locomotion patterns of single flies are
      characterized by bursts of activity at dawn and dusk. Two distinct clusters of
      clock neurons-morning oscillators (M cells) and evening oscillators (E cells)-are
      largely responsible for these activity bursts. In contrast, male-female pairs of
      flies follow a distinct pattern, most notably characterized by an activity trough
      at dusk followed by a high level of male courtship during the night. This male
      sex drive rhythm (MSDR) is mediated by the M cells along with DN1 neurons, a
      cluster of clock neurons located in the dorsal posterior region of the brain.
      Here we report that males lacking Salt-inducible kinase 3 (SIK3) expression in M
      cells exhibit a short period of MSDR but a long period of single-fly locomotor
      rhythm (SLR). Moreover, lack of Sik3 in M cells decreases the amplitude of PERIOD
      (PER) cycling in DN1 neurons, suggesting that SIK3 non-cell-autonomously
      regulates DN1 neurons' molecular clock. We also show that Sik3 reduction
      interferes with circadian nucleocytoplasmic shuttling of Histone deacetylase 4
      (HDAC4), a SIK3 phosphorylation target, in clock neurons and that constitutive
      HDAC4 localization in the nucleus shortens the period of MSDR. Taking these
      findings together, we conclude that SIK3-HDAC4 signaling in M cells regulates
      MSDR by regulating the molecular oscillation in DN1 neurons.

PMID- 28743755
TI  - Ubiquitination of exposed glycoproteins by SCFFBXO27 directs damaged lysosomes
      for autophagy.
AB  - Ubiquitination functions as a signal to recruit autophagic machinery to damaged
      organelles and induce their clearance. Here, we report the characterization of
      FBXO27, a glycoprotein-specific F-box protein that is part of the SCF
      (SKP1/CUL1/F-box protein) ubiquitin ligase complex, and demonstrate that
      SCFFBXO27 ubiquitinates glycoproteins in damaged lysosomes to regulate autophagic
      machinery recruitment. Unlike F-box proteins in other SCF complexes, FBXO27 is
      subject to N-myristoylation, which localizes it to membranes, allowing it to
      accumulate rapidly around damaged lysosomes. We also screened for proteins that
      are ubiquitinated upon lysosomal damage, and identified two SNARE proteins, VAMP3
      and VAMP7, and five lysosomal proteins, LAMP1, LAMP2, GNS, PSAP, and TMEM192.
      Ubiquitination of all glycoproteins identified in this screen increased upon
      FBXO27 overexpression. We found that the lysosomal protein LAMP2, which is
      ubiquitinated preferentially on lysosomal damage, enhances autophagic machinery
      recruitment to damaged lysosomes. Thus, we propose that SCFFBXO27 ubiquitinates
      glycoproteins exposed upon lysosomal damage to induce lysophagy.

PMID- 28743756
TI  - On the question of fractal packing structure in metallic glasses.
AB  - This work addresses the long-standing debate over fractal models of packing
      structure in metallic glasses (MGs). Through detailed fractal and percolation
      analyses of MG structures, derived from simulations spanning a range of
      compositions and quenching rates, we conclude that there is no fractal atomic
      level structure associated with the packing of all atoms or solute-centered
      clusters. The results are in contradiction with conclusions derived from previous
      studies based on analyses of shifts in radial distribution function and structure
      factor peaks associated with volume changes induced by pressure and compositional
      variations. The interpretation of such shifts is shown to be challenged by the
      heterogeneous nature of MG structure and deformation at the atomic scale.
      Moreover, our analysis in the present work illustrates clearly the percolation
      theory applied to MGs, for example, the percolation threshold and characteristics
      of percolation clusters formed by subsets of atoms, which can have important
      consequences for structure-property relationships in these amorphous materials.

PMID- 28743757
TI  - Lipid droplet size and location in human skeletal muscle fibers are associated
      with insulin sensitivity.
AB  - In skeletal muscle, an accumulation of lipid droplets (LDs) in the subsarcolemmal
      space is associated with insulin resistance, but the underlying mechanism is not
      clear. We aimed to investigate how the size, number, and location of LDs are
      associated with insulin sensitivity and muscle fiber types and are regulated by
      aerobic training and treatment with an erythropoiesis-stimulating agent (ESA) in
      healthy young untrained men. LD analyses were performed by quantitative
      transmission electron microscopy, and insulin sensitivity was assessed by a
      hyperinsulinemic-euglycemic clamp. At baseline, we found that only the diameter
      (and not the number) of individual subsarcolemmal LDs was negatively associated
      with insulin sensitivity (R2 = 0.20, P = 0.03, n = 29). Despite 34% (P = 0.004)
      fewer LDs, the diameter of individual subsarcolemmal LDs was 20% (P = 0.0004)
      larger in type 2 fibers than in type 1 fibers. Furthermore, aerobic training
      decreased the size of subsarcolemmal LDs in the type 2 fibers, and ESA treatment
      lowered the number of both intermyofibrillar and subsarcolemmal LDs in the type 1
      fibers. In conclusion, the size of individual subsarcolemmal LDs may be involved
      in the mechanism by which LDs are associated with insulin resistance in skeletal
      muscle.

PMID- 28743758
TI  - ASHP national survey of pharmacy practice in hospital settings: Prescribing and
      transcribing-2016.
AB  - PURPOSE: The results of the 2016 ASHP national survey of pharmacy practice in
      hospital settings are presented. METHODS: A stratified random sample of pharmacy
      directors at 1,315 general and children's medical-surgical hospitals in the
      United States were surveyed using a mixed-mode method offering a choice of
      completing a paper survey or an online survey. IMS Health supplied data on
      hospital characteristics; the survey sample was drawn from IMS's hospital
      database. RESULTS: The survey response rate was 29.8%. Drug policy development by
      pharmacy and therapeutics committees continues to be an important strategy for
      improving prescribing. Strict formulary systems are maintained in 63.0% of
      hospitals, and 89.7% of hospitals use clinical practice guidelines that include
      medications. Pharmacists have the authority to order laboratory tests in 89.9% of
      hospitals and order medications in 86.8% of hospitals. Therapeutic interchange
      policies are used in 89.2% of hospitals. Electronic health records (EHRs) have
      been implemented partially or completely in most hospitals (99.1%). Computerized
      prescriber-order-entry systems with clinical decision support are used in 95.6%
      of hospitals, and 92.6% of hospitals have barcode-assisted medication
      administration systems. Transitions-of-care programs are increasing in number,
      with 34.6% of hospitals now offering discharge prescription services. Pharmacists
      practice in 39.5% of hospital ambulatory or primary care clinics. The most common
      service offered by pharmacists to outpatients is anticoagulation management
      (26.0%). When pharmacists practice in ambulatory care clinics, 64.5% have
      prescribing authority through collaborative practice agreements. CONCLUSION:
      Pharmacists continue to expand their role in improving the prescribing of
      medications in both hospital and outpatient settings. The adoption of EHRs and
      medication-use technologies has contributed to this growth.

PMID- 28743759
TI  - Anatolian origins and diversification of Aethionema, the sister lineage of the
      core Brassicaceae.
AB  - PREMISE OF THE STUDY: The Irano-Turanian region harbors three biodiversity
      hotspots and ~25% of Brassicaceae species are endemic to the region. Aethionema
      (~61 species) is the sister lineage to the core Brassicaceae and occurs mainly in
      the Irano-Turanian region. The evolutionary important position of Aethionema
      makes it an ideal reference for broader comparative genetics and genomics. To
      understand the evolution of Aethionema, and for a broader understanding of
      crucifer evolution, a time-calibrated phylogenetic tree and biogeographical
      history of the genus is needed. METHODS: Seventy-six plastome coding regions and
      nuclear rDNA genes, mainly from herbarium material, covering 75% of all
      Aethionema species, were used to resolve a time-calibrated Aethionema phylogeny.
      The different clades were characterized based on four morphological characters.
      The ancestral area of Aethionema was estimated with historical biogeographical
      analyses. KEY RESULTS: Three well-supported major clades within Aethionema were
      resolved. The ancestral area reconstruction and divergence-time estimates are
      consistent with major dispersal events during the Pliocene from the Anatolian
      Diagonal. CONCLUSIONS: We find that most Aethionema lineages originated along the
      Anatolian Diagonal, a floristic bridge connecting the east to the west, during
      the Pliocene. The dispersal of Aethionema correlates with the local geological
      events, such as the uplift of the Anatolian and Iranian plateaus and the
      formation of the major mountain ranges of the Irano-Turanian region. Knowing the
      paleo-ecological context for the evolution of Aethionema, in addition to the
      other lineages of Brassicaceae, facilitates our broader understanding for trait
      evolution and species diversification across the Brassicaceae.

PMID- 28743760
TI  - High growth temperatures and high soil nitrogen do not alter differences in CO2
      assimilation between invasive Phalaris arundinacea (reed canarygrass) and Carex
      stricta (tussock sedge).
AB  - PREMISE OF THE STUDY: Global change in temperature and soil nitrogen availability
      could affect plant community composition, potentially giving an advantage to
      invasive species compared to native species. We addressed how high temperatures
      affected CO2 assimilation parameters for invasive Phalaris arundinacea and a
      sedge, Carex stricta, it displaces, in natural and controlled environments.
      METHODS: Photosynthetic parameters were measured in a wetland in Indiana, USA
      during the abnormally warm year of 2012. In a growth chamber, photosynthetic
      parameters were measured on the plants grown under three levels of nitrogen and
      exposed to optimum temperatures followed by 2012-like summer conditions and then
      hot temperatures with an autumn-like photoperiod. KEY RESULTS: In the wetland, C.
      stricta exhibited signs of midsummer leaf senescence, whereas P. arundinacea
      maintained CO2 assimilation at ambient pCO2 (Aamb) through mid-October. In the
      chamber, 2012-like conditions reduced Aamb for both species through reductions in
      maximum carboxylation (Vcmax) and electron transport (Jmax) without further
      change during subsequent hot, autumn-like conditions, whereas the quantum
      efficiency of carbon assimilation (qe) declined throughout the experiment.
      However, P. arundinacea had higher values of Aamb, Jmax, and qe than C. stricta.
      A general, the positive effect of increasing nitrogen availability occurred for
      photosynthetic processes for both species in hot conditions. CONCLUSIONS: Our
      data suggest that C. stricta is more susceptible to excessive light stress than
      P. arundinacea during hot, sunny periods, leading to leaf senescence. Field
      confirmation of this idea is needed, but frequent heat waves should favor P.
      arundinacea over C. stricta with or without eutrophication.

PMID- 28743761
TI  - Naturally Segregating Variation at Ugt86Dd Contributes to Nicotine Resistance in
      Drosophila melanogaster.
AB  - Identifying the sequence polymorphisms underlying complex trait variation is a
      key goal of genetics research, since knowing the precise causative molecular
      events allows insight into the pathways governing trait variation. Genetic
      analysis of complex traits in model systems regularly starts by constructing QTL
      maps, but generally fails to identify causative sequence polymorphisms.
      Previously we mapped a series of QTL contributing to resistance to nicotine in a
      Drosophila melanogaster multiparental mapping resource and here use a battery of
      functional tests to resolve QTL to the molecular level. One large-effect QTL
      resided over a cluster of UDP-glucuronosyltransferases, and quantitative
      complementation tests using deficiencies eliminating subsets of these
      detoxification genes revealed allelic variation impacting resistance. RNAseq
      showed that Ugt86Dd had significantly higher expression in genotypes that are
      more resistant to nicotine, and anterior midgut-specific RNA interference (RNAi)
      of this gene reduced resistance. We discovered a segregating 22-bp frameshift
      deletion in Ugt86Dd, and accounting for the InDel during mapping largely
      eliminates the QTL, implying the event explains the bulk of the effect of the
      mapped locus. CRISPR/Cas9 editing of a relatively resistant genotype to generate
      lesions in Ugt86Dd that recapitulate the naturally occurring putative loss-of
      function allele, leads to a large reduction in resistance. Despite this major
      effect of the deletion, the allele appears to be very rare in wild-caught
      populations and likely explains only a small fraction of the natural variation
      for the trait. Nonetheless, this putatively causative coding InDel can be a
      launchpad for future mechanistic exploration of xenobiotic detoxification.

PMID- 28743762
TI  - Mitotic Gene Conversion Tracts Associated with Repair of a Defined Double-Strand
      Break in Saccharomyces cerevisiae.
AB  - Mitotic recombination between homologous chromosomes leads to the uncovering of
      recessive alleles through loss of heterozygosity. In the current study, a defined
      double-strand break was used to initiate reciprocal loss of heterozygosity
      between diverged homologs of chromosome IV in Saccharomyces cerevisiae These
      events resulted from the repair of two broken chromatids, one of which was
      repaired as a crossover and the other as a noncrossover. Associated gene
      conversion tracts resulting from the donor-directed repair of mismatches formed
      during strand exchange (heteroduplex DNA) were mapped using microarrays. Gene
      conversion tracts associated with individual crossover and noncrossover events
      were similar in size and position, with half of the tracts being unidirectional
      and mapping to only one side of the initiating break. Among crossover events,
      this likely reflected gene conversion on only one side of the break, with
      restoration-type repair occurring on the other side. For noncrossover events, an
      ectopic system was used to directly compare gene conversion tracts produced in a
      wild-type strain to heteroduplex DNA tracts generated in the absence of the Mlh1
      mismatch-repair protein. There was a strong bias for unidirectional tracts in the
      absence, but not in the presence, of Mlh1 This suggests that mismatch repair acts
      on heteroduplex DNA that is only transiently present in noncrossover
      intermediates of the synthesis dependent strand annealing pathway. Although the
      molecular features of events associated with loss of heterozygosity generally
      agreed with those predicted by current recombination models, there were
      unexpected complexities in associated gene conversion tracts.

PMID- 28743763
TI  - A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K+
      channels in carbon monoxide-induced proarrhythmic early afterdepolarizations.
AB  - Exposure to CO causes early afterdepolarization arrhythmias. Previous studies in
      rats have indicated that arrhythmias arose as a result of augmentation of the
      late Na+ current. The purpose of the present study was to examine the basis for
      CO-induced arrhythmias in guinea pig myocytes in which action potentials (APs)
      more closely resemble those of human myocytes. Whole-cell current- and voltage
      clamp recordings were made from isolated guinea pig myocytes as well as from
      human embryonic kidney 293 (HEK293) cells that express wild-type or a C723S
      mutant form of ether-a-go-go-related gene (ERG; Kv11.1). We also monitored the
      formation of peroxynitrite (ONOO-) in HEK293 cells fluorimetrically. CO-applied
      as the CO-releasing molecule, CORM-2-prolonged the APs and induced early
      afterdepolarizations in guinea pig myocytes. In HEK293 cells, CO inhibited wild
      type, but not C723S mutant, Kv11.1 K+ currents. Inhibition was prevented by an
      antioxidant, mitochondrial inhibitors, or inhibition of NO formation. CO also
      raised ONOO- levels, an effect that was reversed by the ONOO- scavenger, FeTPPS
      [5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrinato-iron(III)], which also
      prevented the CO inhibition of Kv11.1 currents and abolished the effects of CO on
      Kv11.1 tail currents and APs in guinea pig myocytes. Our data suggest that CO
      induces arrhythmias in guinea pig cardiac myocytes via the ONOO--mediated
      inhibition of Kv11.1 K+ channels.-Al-Owais, M. M., Hettiarachchi, N. T., Kirton,
      H. M., Hardy, M. E., Boyle, J. P., Scragg, J. L., Steele, D. S., Peers, C. A key
      role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K+ channels in
      carbon monoxide-induced proarrhythmic early afterdepolarizations.

PMID- 28743764
TI  - Redox Control of Aphid Resistance through Altered Cell Wall Composition and
      Nutritional Quality.
AB  - The mechanisms underpinning plant perception of phloem-feeding insects,
      particularly aphids, remain poorly characterized. Therefore, the role of
      apoplastic redox state in controlling aphid infestation was explored using
      transgenic tobacco (Nicotiana tabacum) plants that have either high (PAO) or low
      (TAO) ascorbate oxidase (AO) activities relative to the wild type. Only a small
      number of leaf transcripts and metabolites were changed in response to genotype,
      and cell wall composition was largely unaffected. Aphid fecundity was decreased
      significantly in TAO plants compared with other lines. Leaf sugar levels were
      increased and maximum extractable AO activities were decreased in response to
      aphids in all genotypes. Transcripts encoding the Respiratory Burst Oxidase
      Homolog F, signaling components involved in ethylene and other hormone-mediated
      pathways, photosynthetic electron transport components, sugar, amino acid, and
      cell wall metabolism, were increased significantly in the TAO plants in response
      to aphid perception relative to other lines. The levels of galactosylated
      xyloglucan were decreased significantly in response to aphid feeding in all the
      lines, the effect being the least in the TAO plants. Similarly, all lines
      exhibited increases in tightly bound (1->4)-beta-galactan. Taken together, these
      findings identify AO-dependent mechanisms that limit aphid infestation.

PMID- 28743765
TI  - Higher Novel L-Cys Degradation Activity Results in Lower Organic-S and Biomass in
      Sarcocornia than the Related Saltwort, Salicornia.
AB  - Salicornia and Sarcocornia are almost identical halophytes whose edible succulent
      shoots hold promise for commercial production in saline water. Enhanced sulfur
      nutrition may be beneficial to crops naturally grown on high sulfate. However,
      little is known about sulfate nutrition in halophytes. Here we show that
      Salicornia europaea (ecotype RN) exhibits a significant increase in biomass and
      organic-S accumulation in response to supplemental sulfate, whereas Sarcocornia
      fruticosa (ecotype VM) does not, instead exhibiting increased sulfate
      accumulation. We investigated the role of two pathways on organic-S and biomass
      accumulation in Salicornia and Sarcoconia: the sulfate reductive pathway that
      generates Cys and l-Cys desulfhydrase that degrades Cys to H2S, NH3, and
      pyruvate. The major function of O-acetyl-Ser-(thiol) lyase (OAS-TL; EC 2.5.1.47)
      is the formation of l-Cys, but our study shows that the OAS-TL A and OAS-TL B of
      both halophytes are enzymes that also degrade l-Cys to H2S. This activity was
      significantly higher in Sarcocornia than in Salicornia, especially upon sulfate
      supplementation. The activity of the sulfate reductive pathway key enzyme,
      adenosine 5'-phosphosulfate reductase (APR, EC 1.8.99.2), was significantly
      higher in Salicornia than in Sarcocornia These results suggest that the low
      organic-S level in Sarcocornia is the result of high l-Cys degradation rate by
      OAS-TLs, whereas the greater organic-S and biomass accumulation in Salicornia is
      the result of higher APR activity and low l-Cys degradation rate, resulting in
      higher net Cys biosynthesis. These results present an initial road map for
      halophyte growers to attain better growth rates and nutritional value of
      Salicornia and Sarcocornia.

PMID- 28743766
TI  - The evolution of duplicate gene expression in mammalian organs.
AB  - Gene duplications generate genomic raw material that allows the emergence of
      novel functions, likely facilitating adaptive evolutionary innovations. However,
      global assessments of the functional and evolutionary relevance of duplicate
      genes in mammals were until recently limited by the lack of appropriate
      comparative data. Here, we report a large-scale study of the expression evolution
      of DNA-based functional gene duplicates in three major mammalian lineages
      (placental mammals, marsupials, egg-laying monotremes) and birds, on the basis of
      RNA sequencing (RNA-seq) data from nine species and eight organs. We observe
      dynamic changes in tissue expression preference of paralogs with different
      duplication ages, suggesting differential contribution of paralogs to specific
      organ functions during vertebrate evolution. Specifically, we show that paralogs
      that emerged in the common ancestor of bony vertebrates are enriched for genes
      with brain-specific expression and provide evidence for differential forces
      underlying the preferential emergence of young testis- and liver-specific
      expressed genes. Further analyses uncovered that the overall spatial expression
      profiles of gene families tend to be conserved, with several exceptions of
      pronounced tissue specificity shifts among lineage-specific gene family
      expansions. Finally, we trace new lineage-specific genes that may have
      contributed to the specific biology of mammalian organs, including the little
      studied placenta. Overall, our study provides novel and taxonomically broad
      evidence for the differential contribution of duplicate genes to tissue-specific
      transcriptomes and for their importance for the phenotypic evolution of
      vertebrates.

PMID- 28743767
TI  - Pneumomediastinum and pneumorrhachis from recreational nitrous oxide inhalation:
      no laughing matter.

PMID- 28743768
TI  - A central venous catheter that revealed a vascular paradox.

PMID- 28743769
TI  - Betrixaban approved as oral VTE preventive.

PMID- 28743770
TI  - Guideline highlights role of hypertension control in preventing heart failure.

PMID- 28743772
TI  - Legislative year in Indiana ends with big wins for pharmacy.

PMID- 28743773
TI  - Correction.

PMID- 28743774
TI  - Predicting drug price increases: How much this year?

PMID- 28743775
TI  - Iatrogenic salt overdosage in 2 children.

PMID- 28743776
TI  - New pharmacy-specific Medical Subject Headings included in the 2017 database.

PMID- 28743777
TI  - Monitoring clinical decision support in the electronic health record.

PMID- 28743778
TI  - Fracture risk associated with common medications used in treating type 2 diabetes
      mellitus.
AB  - PURPOSE: Published data on the risk of bone fractures associated with medications
      used for the treatment of type 2 diabetes mellitus are summarized. SUMMARY: A
      systematic literature search identified 108 publications on controlled trials and
      6 meta-analyses addressing the potential for fractures with the use of 7 commonly
      used antidiabetic classes: thiazolidinediones (TZDs), sodium-glucose
      cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) agonists,
      dipeptidyl peptidase-4 (DPP-4) inhibitors, biguanides, insulin, and
      sulfonylureas. Among all the classes of agents evaluated, only TZDs have been
      clearly linked to significantly increased fracture risk (number needed to harm
      [NNH], 99 in one meta-analysis and 172 in another meta-analysis) and only in
      female patients. Interim data from an ongoing large placebo-controlled trial
      suggest that use of the SGLT2 inhibitor canagliflozin may be associated with an
      elevated rate of fractures (absolute risk increase, 1.4%; NNH, 71) and decreased
      total-hip bone mineral density. Published data regarding the other evaluated
      classes of agents generally show no effect on fracture risk; some evidence
      suggests a small bone-protective effect with the use of DPP-4 inhibitors.
      CONCLUSION: In patients with type 2 diabetes mellitus, evidence is strongest
      that, among antidiabetic drugs, TZDs increase the risk of bone fractures; thus,
      TZDs should be used with caution in women. Canagliflozin is the only SGLT2
      inhibitor linked to an increased fracture rate. Metformin, sulfonylureas,
      insulin, DPP-4 inhibitors, and GLP-1 agonists appear to have overall neutral
      effects on bone fractures.

PMID- 28743779
TI  - Treatment of pulmonary embolism with argatroban and ultrasound-assisted catheter
      directed thrombolysis with alteplase in a patient with heparin-induced
      thrombocytopenia.
AB  - PURPOSE: Successful ultrasound-assisted catheter-directed thrombolysis (USAT)
      with low-dose alteplase and argatroban in a patient with bilateral pulmonary
      embolism (PE) secondary to heparin-induced thrombocytopenia (HIT) is reported.
      SUMMARY: HIT is a life-threatening complication associated with a high risk of
      thromboembolism. Systemic anticoagulation for the treatment of thrombosis may not
      be sufficient in the presence of PE. Catheter-directed treatment may be indicated
      in patients with PE and associated right ventricular dysfunction. Literature
      describing the use of nonheparin anticoagulation with catheter-directed
      thrombolysis in the setting of HIT, particularly in the context of PE, is
      limited. A 76-year-old Caucasian woman with recent cardiac surgery was
      hospitalized with bilateral PE. Unfractionated heparin was initiated, but the
      patient was switched to argatroban upon suspicion of HIT due to recent heparin
      exposure. The patient clinically improved and was switched to rivaroxaban on
      hospital day 7 for long-term anticoagulation. She developed worsening dyspnea on
      hospital day 9, and a computed tomography angiogram revealed an increased clot
      burden. On hospital day 12, the patient underwent USAT with alteplase and
      argatroban using the EkoSonic Endovascular System (EKOS Corporation, Bothell,
      WA). The catheters and sheaths were removed after approximately 20 hours, and the
      patient had marked hemodynamic improvement with reduced bilateral pulmonary
      arterial pressure. She was transitioned to warfarin therapy and discharged on
      hospital day 19. CONCLUSION: A woman with HIT and bilateral PE was successfully
      treated with the combination of argatroban and USAT with alteplase.

PMID- 28743780
TI  - Supply chain optimization at an academic medical center.
AB  - PURPOSE: A successful supply chain optimization project that leveraged
      technology, engineering principles, and a technician workflow redesign in the
      setting of a growing health system is described. SUMMARY: With continued rises in
      medication costs, medication inventory management is increasingly important.
      Proper management of central pharmacy inventory and floor-stock inventory in
      automated dispensing cabinets (ADCs) can be challenging. In an effort to improve
      control of inventory costs in the central pharmacy of a large academic medical
      center, the pharmacy department implemented a supply chain optimization project
      in collaboration with the medical center's inhouse team of experts on process
      improvement and industrial engineering. The project had 2 main components: (1)
      upgrading and reconfiguring carousel technology within an expanded central
      pharmacy footprint to generate accurate floor-stock inventory replenishment
      reports, which resulted in efficiencies within the medication-use system, and (2)
      implementing a technician workflow redesign and algorithm to right-size the ADC
      inventory, which decreased inventory stockouts (i.e., incidents of depletion of
      medication stock) and improved ADC user satisfaction. CONCLUSION: Through a
      multifaceted approach to inventory management, the number of stockouts per month
      was decreased and ADC inventory was optimized, resulting in a one-time inventory
      cost savings of $220,500.

PMID- 28743781
TI  - The case for philosophy in pharmacy education.

PMID- 28743783
TI  - Rethinking the nonprofit foundation: an emerging niche in the rare disease
      ecosystem.

PMID- 28743782
TI  - 18F-AV-1451 and CSF T-tau and P-tau as biomarkers in Alzheimer's disease.
AB  - To elucidate the relationship between cerebrospinal fluid (CSF) total-tau (T-tau)
      and phosphorylated tau (P-tau) with the tau PET ligand 18F-AV-1451 in Alzheimer's
      disease (AD), we examined 30 cognitively healthy elderly (15 with preclinical
      AD), 14 prodromal AD, and 39 AD dementia patients. CSF T-tau and P-tau were
      highly correlated (R = 0.92, P < 0.001), but they were only moderately associated
      with retention of 18F-AV-1451, and mainly in demented AD patients. 18F-AV-1451,
      but not CSF T-tau or P-tau, was strongly associated with atrophy and cognitive
      impairment. CSF tau was increased in preclinical AD, despite normal 18F-AV-1451
      retention. However, not all dementia AD patients exhibited increased CSF tau,
      even though 18F-AV-1451 retention was always increased at this disease stage. We
      conclude that CSF T-tau and P-tau mainly behave as biomarkers of "disease state",
      since they appear to be increased in many cases of AD at all disease stages,
      already before the emergence of tau aggregates. In contrast, 18F-AV-1451 is a
      biomarker of "disease stage", since it is increased in clinical stages of the
      disease, and is associated with brain atrophy and cognitive decline.

PMID- 28743785
TI  - BubR1 Insufficiency Results in Decreased Macrophage Proliferation and Attenuated
      Atherogenesis in Apolipoprotein E-Deficient Mice.

PMID- 28743784
TI  - Spironolactone is an antagonist of NRG1-ERBB4 signaling and schizophrenia
      relevant endophenotypes in mice.
AB  - Enhanced NRG1-ERBB4 signaling is a risk pathway in schizophrenia, and
      corresponding mouse models display several endophenotypes of the disease.
      Nonetheless, pathway-directed treatment strategies with clinically applicable
      compounds have not been identified. Here, we applied a cell-based assay using the
      split TEV technology to screen a library of clinically applicable compounds to
      identify modulators of NRG1-ERBB4 signaling for repurposing. We recovered
      spironolactone, known as antagonist of corticosteroids, as an inhibitor of the
      ERBB4 receptor and tested it in pharmacological and biochemical assays to assess
      secondary compound actions. Transgenic mice overexpressing Nrg1 type III display
      cortical Erbb4 hyperphosphorylation, a condition observed in postmortem brains
      from schizophrenia patients. Spironolactone treatment reverted
      hyperphosphorylation of activated Erbb4 in these mice. In behavioral tests,
      spironolactone treatment of Nrg1 type III transgenic mice ameliorated
      schizophrenia-relevant behavioral endophenotypes, such as reduced sensorimotor
      gating, hyperactivity, and impaired working memory. Moreover, spironolactone
      increases spontaneous inhibitory postsynaptic currents in cortical slices
      supporting an ERBB4-mediated mode-of-action. Our findings suggest that
      spironolactone, a clinically safe drug, provides an opportunity for new treatment
      options for schizophrenia.

PMID- 28743786
TI  - Outcomes of Patients Presenting With Clinical Indices of Spontaneous Reperfusion
      in ST-Elevation Acute Coronary Syndrome Undergoing Deferred Angiography.
AB  - BACKGROUND: Few data are available regarding the optimal management of ST
      elevation myocardial infarction patients with clinically defined spontaneous
      reperfusion (SR). We report on the characteristics and outcomes of patients with
      SR in the primary percutaneous coronary intervention era, and assess whether
      immediate reperfusion can be deferred. METHODS AND RESULTS: Data were drawn from
      a prospective nationwide survey, ACSIS (Acute Coronary Syndrome Israeli Survey).
      Definition of SR was predefined as both (1) >=70% reduction in ST-segment
      elevation on consecutive ECGs and (2) >=70% resolution of pain. Of 2361
      consecutive ST-elevation-acute coronary syndrome patients in Killip class 1, 405
      (17%) were not treated with primary reperfusion therapy because of SR.
      Intervention in SR patients was performed a median of 26 hours after admission.
      These patients were compared with the 1956 ST-elevation myocardial infarction
      patients who underwent primary reperfusion with a median door-to-balloon of 66
      minutes (interquartile range 38-106). Baseline characteristics were similar
      except for slightly higher incidence of renal dysfunction and prior angina
      pectoris in SR patients. Time from symptom onset to medical contact was
      significantly greater in SR patients. Patients with SR had significantly less in
      hospital heart failure (4% versus 11%) and cardiogenic shock (0% versus 2%)
      (P<0.01 for all). No significant differences were found in in-hospital mortality
      (1% versus 2%), 30-day major cardiac events (4% versus 4%), and mortality at 30
      days (1% versus 2%) and 1 year (4% versus 4%). CONCLUSIONS: Patients with
      clinically defined SR have a favorable prognosis. Deferring immediate
      intervention seems to be safe in patients with clinical indices of spontaneous
      reperfusion.

PMID- 28743787
TI  - ISAR-PEBIS (Paclitaxel-Eluting Balloon Versus Conventional Balloon Angioplasty
      for In-Stent Restenosis of Superficial Femoral Artery): A Randomized Trial.
AB  - BACKGROUND: Paclitaxel-eluting balloon (PEB) angioplasty has superior efficacy
      compared with conventional balloon angioplasty (BA) for de novo lesions of
      superficial femoral artery (SFA). Studies investigating the angiographic and
      clinical performance of PEB angioplasty versus BA for in-stent restenosis of SFA
      are limited. We performed a randomized trial to investigate angiographic and
      clinical performance of PEB versus BA for in-stent restenosis of SFA. METHODS AND
      RESULTS: Patients with symptomatic in-stent restenosis of SFA were randomly
      assigned to either PEB or BA at 2 centers in Munich, Germany. The primary end
      point was the percentage diameter stenosis at 6- to 8-month follow-up
      angiography. Secondary end points were the rate of binary restenosis at follow-up
      angiography and target lesion revascularization, target vessel thrombosis,
      ipsilateral amputation, bypass surgery of the affected limb, and all-cause
      mortality at 24-month follow-up. Seventy patients were assigned to PEB (n=36) or
      BA (n=34). Mean lesion length was 139+/-67 mm, and roughly one third of lesions
      were completely occluded at the time of the index procedure. At control
      angiography, the percentage diameter stenosis (44+/-33% versus 65+/-33%, P=0.01)
      and binary restenosis were significantly reduced with PEB versus BA (30% versus
      59%, P=0.03). At 24-month follow-up, PEB was associated with a significant
      reduction of target lesion revascularization in comparison to BA (19% versus 50%,
      P=0.007). There was no difference with respect to other outcomes of interest.
      CONCLUSIONS: In patients with in-stent restenosis of SFA, a percutaneous therapy
      with PEB compared with BA has superior angiographic performance at 6 to 8 months
      and improved clinical efficacy up to 24-month follow-up. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01083394.

PMID- 28743788
TI  - Adherence to Antihypertensive Medications and Stroke Risk: A Dose-Response Meta
      Analysis.
AB  - BACKGROUND: Inconsistent findings have been obtained for previous studies
      evaluating the association between antihypertensive medication (AHM) adherence
      and the risk of stroke. This dose-response meta-analysis was designed to
      investigate the association between AHM adherence and stroke risk. METHODS AND
      RESULTS: MEDLINE and Embase databases were systematically searched to identify
      relevant studies. The quantification of adherence to AHM was calculated as the
      percentage of the sum of days with AHM actually taken divided by the total number
      of days in a specific period. Summary relative risks (RR) and 95% CIs were
      estimated using a random-effects model. Stratified and dose-response analyses
      were also performed. A total of 18 studies with 1 356 188 participants were
      included. The summary RR of stroke for the highest compared with the lowest AHM
      adherence level was 0.73 (95% CI, 0.67-0.79). Stratified by stroke subtype, a
      higher AHM adherence was associated with lower risks of ischemic stroke (RR,
      0.74; 95% CI, 0.69-0.79) and hemorrhagic stroke (RR, 0.55; 95% CI, 0.42-0.72).
      Moreover, both fatal (RR, 0.51; 95% CI, 0.36-0.73) and nonfatal stroke (RR, 0.52;
      95% CI, 0.28-0.94) were lower in participants with higher AHM adherence. The
      results of a dose-response analysis indicated that a 20% increment in AHM
      adherence level was associated with a 9% lower risk of stroke (RR, 0.91; 95% CI,
      0.86-0.96). CONCLUSIONS: Higher AHM adherence is dose-dependently associated with
      a lower risk of stroke in patients with hypertension.

PMID- 28743789
TI  - Serum neurofilament light chain: a biomarker of neuronal injury in vasculitic
      neuropathy.

PMID- 28743790
TI  - The 'right' way or the best way to do the ankle jerk?

PMID- 28743791
TI  - Imaging in acute ischaemic stroke: pearls and pitfalls.
AB  - Prompt and accurate diagnosis is the foundation of acute ischaemic stroke care.
      Multiple positive endovascular thrombectomy trials in ischaemic stroke patients
      with large vessel occlusions have further emphasised this but also added
      complexity to treatment decisions. CT angiography is now routine for patients who
      present with an acute stroke syndrome around the world. Members of the neurology
      and stroke teams (rather than radiologists) are often the first doctors to lay
      eyes on the CT images and are best equipped to integrate the clinical picture
      with the imaging findings. A sound understanding of acute stroke imaging is
      therefore essential for clinicians who work with acute stroke patients. This
      review describes some pearls we have gleaned from our own experience in acute
      stroke imaging as well as some potential follies to be avoided.

PMID- 28743792
TI  - Treatment of the unknown patient: insights from acute stroke.
AB  - When an unidentified patient who cannot communicate presents with symptoms and
      signs suggesting an acute stroke, the decision to thrombolyse is a particular
      challenge. In a time-pressured environment, clinicians need clear thought
      processes for diagnosis and treatment. Ethical considerations, diagnosis,
      identity and previous history, contraindications, time of symptom onset (EDICT)
      can help decision-making in this situation.

PMID- 28743793
TI  - Animal models of MEN1.
AB  - Animal models of cancer have been instrumental in advancing our understanding of
      the biology of tumor initiation and progression, in studying gene function and in
      performing preclinical studies aimed at testing novel therapies. Several animal
      models of the MEN1 syndrome have been generated in different organisms by
      introducing loss-of-function mutations in the orthologues of the human MEN1 gene.
      In this review, we will discuss MEN1 and MEN1-like models in Drosophila, mice and
      rats. These model systems with their specific advantages and limitations have
      contributed to elucidate the function of Menin in tumorigenesis, which turned out
      to be remarkably conserved from flies to mammals, as well as the biology of the
      disease. Mouse models of MEN1 closely resemble the human disease in terms of
      tumor spectrum and associated hormonal changes, although individual tumor
      frequencies are variable. Rats affected by the MENX (MEN1-like) syndrome share
      some features with MEN1 patients albeit they bear a germline mutation in Cdkn1b
      (p27) and not in Men1 Both Men1-knockout mice and MENX rats have been exploited
      for therapy-response studies testing novel drugs for efficacy against
      neuroendocrine tumors (NETs) and have provided promising leads for novel
      therapies. In addition to presenting well-established models of MEN1, we also
      discuss potential models which, if implemented, might broaden even further our
      knowledge of neuroendocrine tumorigenesis. In the future, patient-derived
      xenografts in zebrafish or mice might allow us to expand the tool-box currently
      available for preclinical studies of MEN1-associated tumors.

PMID- 28743794
TI  - Can't see the woods for the trees: exploring the range and connection of tobacco
      industry argumentation in the 2012 UK standardised packaging consultation.
AB  - INTRODUCTION: Transnational tobacco company (TTC) submissions to the 2012 UK
      standardised packaging consultation are studied to examine TTC argumentation in
      the context of Better Regulation practices. METHODS: A content analysis was
      conducted of Philip Morris International and British American Tobacco submissions
      to the 2012 UK consultation. Industry arguments concerning expected costs and
      (contested) benefits of the policy were categorised into themes and frames. The
      inter-relationship between frames through linked arguments was mapped to analyse
      central arguments using an argumentation network. RESULTS: 173 arguments were
      identified. Arguments fell into one of five frames: ineffectiveness, negative
      economic consequences, harm to public health, increased crime or legal
      ramifications. Arguments highlighted high costs to a wide range of groups,
      including government, general public and other businesses. Arguments also
      questioned the public health benefits of standardised packaging and highlighted
      the potential benefits to undeserving groups. An increase in illicit trade was
      the most central argument and linked to the greatest variety of arguments.
      CONCLUSIONS: In policy-making systems characterised by mandatory impact
      assessments and public consultations, the wide range of cost (and contested
      benefits) based arguments highlights the risk of TTCs overloading policy actors
      and causing delays in policy adoption. Illicit trade related arguments are
      central to providing a rationale for these arguments, which include the claim
      that standardised packaging will increase health risks. The strategic importance
      of illicit trade arguments to industry argumentation in public consultations
      underlines the risks of relying on industry data relating to the scale of the
      illicit trade.

PMID- 28743795
TI  - Capturing protein communities by structural proteomics in a thermophilic
      eukaryote.
AB  - The arrangement of proteins into complexes is a key organizational principle for
      many cellular functions. Although the topology of many complexes has been
      systematically analyzed in isolation, their molecular sociology in situ remains
      elusive. Here, we show that crude cellular extracts of a eukaryotic thermophile,
      Chaetomium thermophilum, retain basic principles of cellular organization. Using
      a structural proteomics approach, we simultaneously characterized the abundance,
      interactions, and structure of a third of the C. thermophilum proteome within
      these extracts. We identified 27 distinct protein communities that include 108
      interconnected complexes, which dynamically associate with each other and
      functionally benefit from being in close proximity in the cell. Furthermore, we
      investigated the structure of fatty acid synthase within these extracts by cryoEM
      and this revealed multiple, flexible states of the enzyme in adaptation to its
      association with other complexes, thus exemplifying the need for in situ studies.
      As the components of the captured protein communities are known-at both the
      protein and complex levels-this study constitutes another step forward toward a
      molecular understanding of subcellular organization.

PMID- 28743796
TI  - Sox2 expression in Schwann cells inhibits myelination in vivo and induces influx
      of macrophages to the nerve.
AB  - Correct myelination is crucial for the function of the peripheral nervous system.
      Both positive and negative regulators within the axon and Schwann cell function
      to ensure the correct onset and progression of myelination during both
      development and following peripheral nerve injury and repair. The Sox2
      transcription factor is well known for its roles in the development and
      maintenance of progenitor and stem cell populations, but has also been proposed
      in vitro as a negative regulator of myelination in Schwann cells. We wished to
      test fully whether Sox2 regulates myelination in vivo and show here that, in
      mice, sustained Sox2 expression in vivo blocks myelination in the peripheral
      nerves and maintains Schwann cells in a proliferative non-differentiated state,
      which is also associated with increased inflammation within the nerve. The
      plasticity of Schwann cells allows them to re-myelinate regenerated axons
      following injury and we show that re-myelination is also blocked by Sox2
      expression in Schwann cells. These findings identify Sox2 as a physiological
      regulator of Schwann cell myelination in vivo and its potential to play a role in
      disorders of myelination in the peripheral nervous system.

PMID- 28743797
TI  - Sonic hedgehog from both nerves and epithelium is a key trophic factor for taste
      bud maintenance.
AB  - The integrity of taste buds is intimately dependent on an intact gustatory
      innervation, yet the molecular nature of this dependency is unknown. Here, we
      show that differentiation of new taste bud cells, but not progenitor
      proliferation, is interrupted in mice treated with a hedgehog (Hh) pathway
      inhibitor (HPI), and that gustatory nerves are a source of sonic hedgehog (Shh)
      for taste bud renewal. Additionally, epithelial taste precursor cells express Shh
      transiently, and provide a local supply of Hh ligand that supports taste cell
      renewal. Taste buds are minimally affected when Shh is lost from either tissue
      source. However, when both the epithelial and neural supply of Shh are removed,
      taste buds largely disappear. We conclude Shh supplied by taste nerves and local
      taste epithelium act in concert to support continued taste bud differentiation.
      However, although neurally derived Shh is in part responsible for the dependence
      of taste cell renewal on gustatory innervation, neurotrophic support of taste
      buds likely involves a complex set of factors.

PMID- 28743798
TI  - Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc.
AB  - Morphogen concentration gradients that extend across developmental fields form by
      dispersion from source cells. In the Drosophila wing disc, Hedgehog (Hh) produced
      by posterior compartment cells distributes in a concentration gradient to
      adjacent cells of the anterior compartment. We monitored Hh:GFP after pulsed
      expression, and analyzed the movement and colocalization of Hh, Patched (Ptc) and
      Smoothened (Smo) proteins tagged with GFP or mCherry and expressed at
      physiological levels from bacterial artificial chromosome transgenes. Hh:GFP
      moved to basal subcellular locations prior to release from posterior compartment
      cells that express it, and was taken up by basal cytonemes that extend to the
      source cells. Hh and Ptc were present in puncta that moved along the basal
      cytonemes and formed characteristic apical-basal distributions in the anterior
      compartment cells. The basal cytonemes required diaphanous, SCAR, Neuroglian and
      Synaptobrevin, and both the Hh gradient and Hh signaling declined under
      conditions in which the cytonemes were compromised. These findings show that in
      the wing disc, Hh distributions and signaling are dependent upon basal release
      and uptake, and on cytoneme-mediated movement. No evidence for apical dispersion
      was obtained.

PMID- 28743799
TI  - Non-canonical WOX11-mediated root branching contributes to plasticity in
      Arabidopsis root system architecture.
AB  - Lateral roots (LRs), which originate from the growing root, and adventitious
      roots (ARs), which are formed from non-root organs, are the main contributors to
      the post-embryonic root system in Arabidopsis However, our knowledge of how
      formation of the root system is altered in response to diverse inductive cues is
      limited. Here, we show that WOX11 contributes to root system plasticity. When
      seedlings are grown vertically on medium, WOX11 is not expressed in LR founder
      cells. During AR initiation, WOX11 is expressed in AR founder cells and activates
      LBD16LBD16 also functions in LR formation and is activated in that context by
      ARF7/19 and not by WOX11 This indicates that divergent initial processes that
      lead to ARs and LRs may converge on a similar mechanism for primordium
      development. Furthermore, we demonstrated that when plants are grown in soil or
      upon wounding on medium, the primary root is able to produce both WOX11-mediated
      and non-WOX11-mediated roots. The discovery of WOX11-mediated root-derived roots
      reveals a previously uncharacterized pathway that confers plasticity during the
      generation of root system architecture in response to different inductive cues.

PMID- 28743800
TI  - In vivo genetic cell lineage tracing reveals that oviductal secretory cells self
      renew and give rise to ciliated cells.
AB  - The epithelial lining of the fallopian tube is vital for fertility, providing
      nutrition to gametes and facilitating their transport. It is composed of two
      major cell types: secretory cells and ciliated cells. Interestingly, human
      ovarian cancer precursor lesions primarily consist of secretory cells. It is
      unclear why secretory cells are the dominant cell type in these lesions.
      Additionally, the underlying mechanisms governing fallopian tube epithelial
      homoeostasis are unknown. In the present study, we showed that across the
      different developmental stages of mouse oviduct, secretory cells are the most
      frequently dividing cells of the oviductal epithelium. In vivo genetic cell
      lineage tracing showed that secretory cells not only self-renew, but also give
      rise to ciliated cells. Analysis of a Wnt reporter mouse model and various Wnt
      target genes showed that the Wnt signaling pathway is involved in oviductal
      epithelial homoeostasis. By developing two triple-transgenic mouse models, we
      showed that Wnt/beta-catenin signaling is essential for self-renewal as well as
      the differentiation of secretory cells. In summary, our results provide
      mechanistic insight into oviductal epithelial homoeostasis.

PMID- 28743802
TI  - Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle,
      protects against diet-induced obesity and insulin resistance.
AB  - In addition to controlling blood pressure, cardiac natriuretic peptides (NPs) can
      stimulate lipolysis in adipocytes and promote the "browning" of white adipose
      tissue. NPs may also increase the oxidative capacity of skeletal muscle. To
      unravel the contribution of NP-stimulated metabolism in adipose tissue compared
      to that in muscle in vivo, we generated mice with tissue-specific deletion of the
      NP clearance receptor, NPRC, in adipose tissue (NprcAKO ) or in skeletal muscle
      (NprcMKO ). We showed that, similar to Nprc null mice, NprcAKO mice, but not
      NprcMKO mice, were resistant to obesity induced by a high-fat diet. NprcAKO mice
      exhibited increased energy expenditure, improved insulin sensitivity, and
      increased glucose uptake into brown fat. These mice were also protected from diet
      induced hepatic steatosis and visceral fat inflammation. These findings support
      the conclusion that NPRC in adipose tissue is a critical regulator of energy
      metabolism and suggest that inhibiting this receptor may be an important avenue
      to explore for combating metabolic disease.

PMID- 28743803
TI  - The glucocorticoid-Angptl4-ceramide axis induces insulin resistance through PP2A
      and PKCzeta.
AB  - Chronic glucocorticoid exposure is associated with the development of insulin
      resistance. We showed that glucocorticoid-induced insulin resistance was
      attenuated upon ablation of Angptl4, a glucocorticoid target gene encoding the
      secreted protein angiopoietin-like 4, which mediates glucocorticoid-induced
      lipolysis in white adipose tissue. Through metabolomic profiling, we revealed
      that glucocorticoid treatment increased hepatic ceramide concentrations by
      inducing enzymes in the ceramide synthetic pathway in an Angptl4-dependent
      manner. Angptl4 was also required for glucocorticoids to stimulate the activities
      of the downstream effectors of ceramide, protein phosphatase 2A (PP2A) and
      protein kinase Czeta (PKCzeta). We further showed that knockdown of PP2A or
      inhibition of PKCzeta or ceramide synthesis prevented glucocorticoid-induced
      glucose intolerance in wild-type mice. Moreover, the inhibition of PKCzeta or
      ceramide synthesis did not further improve glucose tolerance in Angptl4-/- mice,
      suggesting that these molecules were major downstream effectors of Angptl4.
      Overall, our study demonstrates the key role of Angptl4 in glucocorticoid
      augmented hepatic ceramide production that induces whole-body insulin resistance.

PMID- 28743804
TI  - Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage
      the Injured Myocardium.
AB  - RATIONALE: Cardiac myocytes derived from pluripotent stem cells have demonstrated
      the potential to mitigate damage of the infarcted myocardium and improve left
      ventricular ejection fraction. However, the mechanism underlying the functional
      benefit is unclear. OBJECTIVE: To evaluate whether the transplantation of cardiac
      lineage differentiated derivatives enhance myocardial viability and restore left
      ventricular ejection fraction more effectively than undifferentiated pluripotent
      stem cells after a myocardial injury. Herein, we utilize novel multimodality
      evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes
      (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac
      myocytes (iCMs) in a murine myocardial injury model. METHODS AND RESULTS:
      Permanent ligation of the left anterior descending coronary artery was induced in
      immunosuppressed mice. Intramyocardial injection was performed with (1) hESCs
      (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14), and (5) PBS control
      (n=10). Left ventricular ejection fraction and myocardial viability, measured by
      cardiac magnetic resonance imaging and manganese-enhanced magnetic resonance
      imaging, respectively, was significantly improved in hCM- and iCM-treated mice
      compared with pluripotent stem cell- or control-treated mice. Bioluminescence
      imaging revealed limited cell engraftment in all treated groups, suggesting that
      the cell secretions may underlie the repair mechanism. To determine the paracrine
      effects of the transplanted cells, cytokines from supernatants from all groups
      were assessed in vitro. Gene expression and immunohistochemistry analyses of the
      murine myocardium demonstrated significant upregulation of the promigratory,
      proangiogenic, and antiapoptotic targets in groups treated with cardiac lineage
      cells compared with pluripotent stem cell and control groups. CONCLUSIONS: This
      study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the
      injured myocardium effectively than undifferentiated stem cells through their
      differential paracrine effects.

PMID- 28743805
TI  - EphrinB2 Regulates Cardiac Fibrosis Through Modulating the Interaction of Stat3
      and TGF-beta/Smad3 Signaling.
AB  - RATIONALE: Cardiac fibrosis is a common feature in left ventricular remodeling
      that leads to heart failure, regardless of the cause. EphrinB2 (erythropoietin
      producing hepatoma interactor B2), a pivotal bidirectional signaling molecule
      ubiquitously expressed in mammals, is crucial in angiogenesis during development
      and disease progression. Recently, EphrinB2 was reported to protect kidneys from
      injury-induced fibrogenesis. However, its role in cardiac fibrosis remains to be
      clarified. OBJECTIVE: We sought to determine the role of EphrinB2 in cardiac
      fibrosis and the underlying mechanisms during the pathological remodeling
      process. METHODS AND RESULTS: EphrinB2 was highly expressed in the myocardium of
      patients with advanced heart failure, as well as in mouse models of myocardial
      infarction and cardiac hypertrophy induced by angiotensin II infusion, which was
      accompanied by myofibroblast activation and collagen fiber deposition. In
      contrast, intramyocardial injection of lentiviruses carrying EphrinB2-shRNA
      ameliorated cardiac fibrosis and improved cardiac function in mouse model of
      myocardial infarction. Furthermore, in vitro studies in cultured cardiac
      fibroblasts demonstrated that EphrinB2 promoted the differentiation of cardiac
      fibroblasts into myofibroblasts in normoxic and hypoxic conditions.
      Mechanistically, the profibrotic effect of EphrinB2 on cardiac fibroblast was
      determined via activating the Stat3 (signal transducer and activator of
      transcription 3) and TGF-beta (transforming growth factor-beta)/Smad3 (mothers
      against decapentaplegic homolog 3) signaling. We further determined that EphrinB2
      modulated the interaction between Stat3 and Smad3 and identified that the MAD
      homology 2 domain of Smad3 and the coil-coil domain and DNA-binding domain of
      Stat3 mediated the interaction. CONCLUSIONS: This study uncovered a previously
      unrecognized profibrotic role of EphrinB2 in cardiac fibrosis, which is achieved
      through the interaction of Stat3 with TGF-beta/Smad3 signaling, implying a
      promising therapeutic target in fibrotic diseases and heart failure.

PMID- 28743806
TI  - The Stress-Inducible Peroxidase TSA2 Underlies a Conditionally Beneficial
      Chromosomal Duplication in Saccharomyces cerevisiae.
AB  - Although chromosomal duplications are often deleterious, in some cases they
      enhance cells' abilities to tolerate specific genetic or environmental
      challenges. Identifying the genes that confer these conditionally beneficial
      effects to particular chromosomal duplications can improve our understanding of
      the genetic and molecular mechanisms that enable certain aneuploidies to persist
      in cell populations and contribute to disease and evolution. Here, we perform a
      screen for spontaneous mutations that improve the tolerance of haploid
      Saccharomyces cerevisiae to hydrogen peroxide. Chromosome IV duplication is the
      most frequent mutation, as well as the only change in chromosomal copy number
      seen in the screen. Using a genetic mapping strategy that involves systematically
      deleting segments of a duplicated chromosome, we show that the chromosome IV's
      duplication effect is largely due to the generation of a second copy of the
      stress-inducible cytoplasmic thioredoxin peroxidase TSA2 Our findings add to a
      growing body of literature that shows the conditionally beneficial effects of
      chromosomal duplication are typically mediated by a small number of genes that
      enhance tolerance to specific stresses when their copy numbers are increased.

PMID- 28743807
TI  - Genome-Wide Screen for Genes Involved in Caenorhabditis elegans Developmentally
      Timed Sleep.
AB  - In Caenorhabditis elegans, Notch signaling regulates developmentally timed sleep
      during the transition from L4 larval stage to adulthood (L4/A) . To identify core
      sleep pathways and to find genes acting downstream of Notch signaling, we
      undertook the first genome-wide, classical genetic screen focused on C. elegans
      developmentally timed sleep. To increase screen efficiency, we first looked for
      mutations that suppressed inappropriate anachronistic sleep in adult hsp::osm-11
      animals overexpressing the Notch coligand OSM-11 after heat shock. We retained
      suppressor lines that also had defects in L4/A developmentally timed sleep,
      without heat shock overexpression of the Notch coligand. Sixteen suppressor lines
      with defects in developmentally timed sleep were identified. One line carried a
      new allele of goa-1; loss of GOA-1 Galphao decreased C. elegans sleep. Another
      line carried a new allele of gpb-2, encoding a Gbeta5 protein; Gbeta5 proteins
      have not been previously implicated in sleep. In other scenarios, Gbeta5 GPB-2
      acts with regulators of G protein signaling (RGS proteins) EAT-16 and EGL-10 to
      terminate either EGL-30 Galphaq signaling or GOA-1 Galphao signaling,
      respectively. We found that loss of Gbeta5 GPB-2 or RGS EAT-16 decreased L4/A
      sleep. By contrast, EGL-10 loss had no impact. Instead, loss of RGS-1 and RGS-2
      increased sleep. Combined, our results suggest that, in the context of L4/A
      sleep, GPB-2 predominantly acts with EAT-16 RGS to inhibit EGL-30 Galphaq
      signaling. These results confirm the importance of G protein signaling in sleep
      and demonstrate that these core sleep pathways function genetically downstream of
      the Notch signaling events promoting sleep.

PMID- 28743808
TI  - Metabolic Compensation of Fitness Costs Is a General Outcome for Antibiotic
      Resistant Pseudomonas aeruginosa Mutants Overexpressing Efflux Pumps.
AB  - It is generally assumed that the acquisition of antibiotic resistance is
      associated with a fitness cost. We have shown that overexpression of the MexEF
      OprN efflux pump does not decrease the fitness of a resistant Pseudomonas
      aeruginosa strain compared to its wild-type counterpart. This lack of fitness
      cost was associated with a metabolic rewiring that includes increased expression
      of the anaerobic nitrate respiratory chain when cells are growing under fully
      aerobic conditions. It was not clear whether this metabolic compensation was
      exclusive to strains overexpressing MexEF-OprN or if it extended to other
      resistant strains that overexpress similar systems. To answer this question, we
      studied a set of P. aeruginosa mutants that independently overexpress the MexAB
      OprM, MexCD-OprJ, or MexXY efflux pumps. We observed increased expression of the
      anaerobic nitrate respiratory chain in all cases, with a concomitant increase in
      NO3 consumption and NO production. These efflux pumps are proton/substrate
      antiporters, and their overexpression may lead to intracellular H+ accumulation,
      which may in turn offset the pH homeostasis. Indeed, all studied mutants showed a
      decrease in intracellular pH under anaerobic conditions. The fastest way to
      eliminate the excess of protons is by increasing oxygen consumption, a feature
      also displayed by all analyzed mutants. Taken together, our results support
      metabolic rewiring as a general mechanism to avoid the fitness costs derived from
      overexpression of P. aeruginosa multidrug efflux pumps. The development of drugs
      that block this metabolic "reaccommodation" might help in reducing the
      persistence and spread of antibiotic resistance elements among bacterial
      populations.IMPORTANCE It is widely accepted that the acquisition of resistance
      confers a fitness cost in such a way that in the absence of antibiotics,
      resistant populations will be outcompeted by susceptible ones. Based on this
      assumption, antibiotic cycling regimes have been proposed in the belief that they
      will reduce the persistence and spread of resistance among bacterial pathogens.
      Unfortunately, trials testing this possibility have frequently failed, indicating
      that resistant microorganisms are not always outcompeted by susceptible ones.
      Indeed, some mutations do not result in a fitness cost, and in case they do, the
      cost may be compensated for by a secondary mutation. Here we describe an
      alternative nonmutational mechanism for compensating for fitness costs, which
      consists of the metabolic rewiring of resistant mutants. Deciphering the
      mechanisms involved in the compensation of fitness costs of antibiotic-resistant
      mutants may help in the development of drugs that will reduce the persistence of
      resistance by increasing said costs.

PMID- 28743809
TI  - Prevention of Ophthalmia Neonatorum Caused by Neisseria gonorrhoeae Using a Fatty
      Acid-Based Formulation.
AB  - Ophthalmia neonatorum, also called neonatal conjunctivitis, acquired during
      delivery can occur in the first 28 days of life. Commonly caused by the bacterial
      pathogen Neisseria gonorrhoeae, infection can lead to corneal scarring,
      perforation of the eye, and blindness. One approach that can be taken to prevent
      the disease is the use of an ophthalmic prophylaxis, which kills the bacteria on
      the surface of the eye shortly after birth. Current prophylaxes are based on
      antibiotic ointments. However, N. gonorrhoeae is resistant to many antibiotics
      and alternative treatments must be developed before the condition becomes
      untreatable. This study focused on developing a fatty acid-based prophylaxis. For
      this, 37 fatty acids or fatty acid derivatives were screened in vitro for fast
      antigonococcal activity. Seven candidates were identified as bactericidal at 1
      mM. These seven were subjected to irritation testing using three separate
      methods: the bovine corneal opacity and permeability (BCOP) test; the hen's egg
      test-chorioallantoic membrane (HET-CAM); and the red blood cell (RBC) lysis
      assay. The candidates were also tested in artificial tear fluid to determine
      whether they were effective in this environment. Four of the candidates remained
      effective. Among these, two lead candidates, monocaprin and myristoleic acid,
      displayed the best potential as active compounds in the development of a fatty
      acid-based prophylaxis for prevention of ophthalmia neonatorum.

PMID- 28743810
TI  - Polymyxin Combinations Combat Escherichia coli Harboring mcr-1 and blaNDM-5:
      Preparation for a Postantibiotic Era.
AB  - The rapid increase of carbapenem resistance in Gram-negative bacteria has
      resurrected the importance of the polymyxin antibiotics. The recent discovery of
      plasmid-mediated polymyxin resistance (mcr-1) in carbapenem-resistant
      Enterobacteriaceae serves as an important indicator that the golden era of
      antibiotics is under serious threat. We assessed the bacterial killing of 15
      different FDA-approved antibiotics alone and in combination with polymyxin B in
      time-killing experiments against Escherichia coli MCR1_NJ, the first reported
      isolate in the United States to coharbor mcr-1 and a New Delhi metallo-beta
      lactamase gene (blaNDM-5). The most promising regimens were advanced to the
      hollow-fiber infection model (HFIM), where human pharmacokinetics for polymyxin
      B, aztreonam, and amikacin were simulated over 240 h. Exposure to polymyxin B
      monotherapy was accompanied by MCR1_NJ regrowth but not resistance amplification
      (polymyxin B MIC from 0 to 240 h [MIC0h to MIC240h] of 4 mg/liter), whereas
      amikacin monotherapy caused regrowth and simultaneous resistance amplification
      (amikacin MIC0h of 4 mg/liter versus MIC240h of >64 mg/liter). No MCR1_NJ
      colonies were observed for any of the aztreonam-containing regimens after 72 h.
      However, HFIM cartridges for both aztreonam monotherapy and the polymyxin B-plus
      aztreonam regimen were remarkably turbid, and the presence of long, filamentous
      MCR1_NJ cells was evident in scanning electron microscopy, suggestive of a
      nonreplicating persister (NRP) phenotype. In contrast, the 3-drug combination of
      polymyxin B, aztreonam, and amikacin provided complete eradication (>8-log10
      CFU/ml reduction) with suppression of resistance and prevention of NRP formation.
      This is the first comprehensive pharmacokinetic/pharmacodynamic study to evaluate
      triple-drug combinations for polymyxin- and carbapenem-resistant E. coli
      coproducing MCR-1 and NDM-5 and will aid in the preparation for a so-called
      "postantibiotic" era.IMPORTANCE A global health crisis may be on the horizon, as
      the golden era of antibiotics is under serious threat. We recently reported the
      first case in the United States of a highly resistant, Escherichia coli so-called
      "superbug" (MCR1_NJ), coharboring two of the most worrying antibiotic resistance
      genes, encoding mobile colistin resistance (mcr-1) and a New Delhi metallo-beta
      lactamase (blaNDM-5). Worryingly, the medical community is vulnerable to this
      emerging bacterial threat because optimal treatment strategies are undefined.
      Here, we report the activity of an optimized combination using simulated human
      doses of commercially available antibiotics against MCR1_NJ. A unique triple
      combination involving a cocktail of polymyxin B, aztreonam, and amikacin
      eradicated the MCR-1- and NDM-5-producing E. coli Each antimicrobial agent
      administered as monotherapy or in double combinations failed to eradicate MCR1_NJ
      at a high inoculum. To our knowledge, this is the first study to propose 3-drug
      therapeutic solutions against superbugs coharboring mcr-1 and blaNDM, seeking to
      prepare clinicians for future occurrences of these pathogens.

PMID- 28743811
TI  - Structural and In Vivo Studies on Trehalose-6-Phosphate Synthase from Pathogenic
      Fungi Provide Insights into Its Catalytic Mechanism, Biological Necessity, and
      Potential for Novel Antifungal Drug Design.
AB  - The disaccharide trehalose is critical to the survival of pathogenic fungi in
      their human host. Trehalose-6-phosphate synthase (Tps1) catalyzes the first step
      of trehalose biosynthesis in fungi. Here, we report the first structures of
      eukaryotic Tps1s in complex with substrates or substrate analogues. The overall
      structures of Tps1 from Candida albicans and Aspergillus fumigatus are
      essentially identical and reveal N- and C-terminal Rossmann fold domains that
      form the glucose-6-phosphate and UDP-glucose substrate binding sites,
      respectively. These Tps1 structures with substrates or substrate analogues reveal
      key residues involved in recognition and catalysis. Disruption of these key
      residues severely impaired Tps1 enzymatic activity. Subsequent cellular analyses
      also highlight the enzymatic function of Tps1 in thermotolerance, yeast-hypha
      transition, and biofilm development. These results suggest that Tps1 enzymatic
      functionality is essential for the fungal stress response and virulence.
      Furthermore, structures of Tps1 in complex with the nonhydrolyzable inhibitor,
      validoxylamine A, visualize the transition state and support an internal return
      like catalytic mechanism that is generalizable to other GT-B-fold retaining
      glycosyltransferases. Collectively, our results depict key Tps1-substrate
      interactions, unveil the enzymatic mechanism of these fungal proteins, and pave
      the way for high-throughput inhibitor screening buttressed and guided by the
      current structures and those of high-affinity ligand-Tps1 complexes.IMPORTANCE
      Invasive fungal diseases have emerged as major threats, resulting in more than
      1.5 million deaths annually worldwide. This epidemic has been further complicated
      by increasing resistance to all major classes of antifungal drugs in the clinic.
      Trehalose biosynthesis is essential for the fungal stress response and virulence.
      Critically, this biosynthetic pathway is absent in mammals, and thus, the two
      enzymes that carry out trehalose biosynthesis, namely, trehalose-6-phosphate
      synthase (Tps1) and trehalose-6-phosphate phosphatase (Tps2), are prominent
      targets for antifungal intervention. Here, we report the first eukaryotic Tps1
      structures from the pathogenic fungi Candida albicans and Aspergillus fumigatus
      in complex with substrates, substrate analogues, and inhibitors. These structures
      reveal key protein-substrate interactions, providing atomic-level scaffolds for
      structure-guided drug design of novel antifungals that target Tps1.

PMID- 28743812
TI  - Horizontal Gene Transfer of Functional Type VI Killing Genes by Natural
      Transformation.
AB  - Horizontal gene transfer (HGT) can have profound effects on bacterial evolution
      by allowing individuals to rapidly acquire adaptive traits that shape their
      strategies for competition. One strategy for intermicrobial antagonism often used
      by Proteobacteria is the genetically encoded contact-dependent type VI secretion
      system (T6SS), a weapon used to kill heteroclonal neighbors by direct injection
      of toxic effectors. Here, we experimentally demonstrate that Vibrio cholerae can
      acquire new T6SS effector genes via horizontal transfer and utilize them to kill
      neighboring cells. Replacement of one or more parental alleles with novel
      effectors allows the recombinant strain to dramatically outcompete its parent.
      Using spatially explicit modeling, we examine how this process could affect the
      ecology and evolution of surface-attached microbial populations. HGT of T6SS
      effector-immunity pairs is risky: transformation brings a cell into conflict with
      its former clone mates but can be adaptive when superior T6SS alleles are
      acquired. More generally, we find that these costs and benefits are not symmetric
      and that high rates of HGT can act as a hedge against competitors with
      unpredictable T6SS efficacy. We conclude that antagonism and horizontal transfer
      drive successive rounds of weapon optimization and selective sweeps, dynamically
      shaping the composition of microbial communities.IMPORTANCE The contact-dependent
      type VI secretion system (T6SS) is frequently used by Proteobacteria to kill
      adjacent competitors. While DNA released by T6 killing can be horizontally
      acquired, it remains untested whether T6 genes themselves can be horizontally
      acquired and then utilized to compete with neighboring cells. Using naturally
      transformable Vibrio cholerae, we provide the first direct empirical support for
      the hypothesis that T6 genes are exchanged horizontally (e.g., from dead
      competitors) and functionally deployed to compete with neighboring cells. Using
      computational simulations, we also demonstrate that high rates of HGT can be
      adaptive, allowing V. cholerae to improve upon existing T6 weaponry and survive
      direct encounters with otherwise superior competitors. We anticipate that our
      evolutionary results are of broad microbiological relevance, applying to many
      bacteria capable of HGT that utilize the T6SS or similar antagonistic systems,
      and highlight the profound impact of HGT in shaping microbial community
      structure.

PMID- 28743813
TI  - Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of
      Antibiotics Targeting LpxC.
AB  - The infectious diseases caused by multidrug-resistant bacteria pose serious
      threats to humankind. It has been suggested that an antibiotic targeting LpxC of
      the lipid A biosynthetic pathway in Gram-negative bacteria is a promising
      strategy for curing Gram-negative bacterial infections. However, experimental
      proof of this concept is lacking. Here, we describe our discovery and
      characterization of a biphenylacetylene-based inhibitor of LpxC, an essential
      enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram
      negative bacteria. The compound LPC-069 has no known adverse effects in mice and
      is effective in vitro against a broad panel of Gram-negative clinical isolates,
      including several multiresistant and extremely drug-resistant strains involved in
      nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one
      of the most severe human diseases, bubonic plague, which is caused by the Gram
      negative bacterium Yersinia pestis Our results demonstrate the safety and
      efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections
      caused by extremely virulent pathogens. The present findings also highlight the
      potential of LpxC inhibitors for clinical development as therapeutics for
      infections caused by multidrug-resistant bacteria.IMPORTANCE The rapid spread of
      antimicrobial resistance among Gram-negative bacilli highlights the urgent need
      for new antibiotics. Here, we describe a new class of antibiotics lacking cross
      resistance with conventional antibiotics. The compounds inhibit LpxC, a key
      enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are
      active in vitro against a broad panel of clinical isolates of Gram-negative
      bacilli involved in nosocomial and community infections. The present study also
      constitutes the first demonstration of the curative treatment of bubonic plague
      by a novel, broad-spectrum antibiotic targeting LpxC. Hence, the data highlight
      the therapeutic potential of LpxC inhibitors against a wide variety of Gram
      negative bacterial infections, including the most severe ones caused by Y. pestis
      and by multidrug-resistant and extensively drug-resistant carbapenemase-producing
      strains.

PMID- 28743814
TI  - Stringent Expression Control of Pathogenic R-body Production in Legume Symbiont
      Azorhizobium caulinodans.
AB  - R bodies are insoluble large polymers consisting of small proteins encoded by reb
      genes and are coiled into cylindrical structures in bacterial cells. They were
      first discovered in Caedibacter species, which are obligate endosymbionts of
      paramecia. Caedibacter confers a killer trait on the host paramecia. R-body
      producing symbionts are released from their host paramecia and kill symbiont-free
      paramecia after ingestion. The roles of R bodies have not been explained in
      bacteria other than CaedibacterAzorhizobium caulinodans ORS571, a microsymbiont
      of the legume Sesbania rostrata, carries a reb operon containing four reb genes
      that are regulated by the repressor PraR. Herein, deletion of the praR gene
      resulted in R-body formation and death of host plant cells. The rebR gene in the
      reb operon encodes an activator. Three PraR binding sites and a RebR binding site
      are present in the promoter region of the reb operon. Expression analyses using
      strains with mutations within the PraR binding site and/or the RebR binding site
      revealed that PraR and RebR directly control the expression of the reb operon and
      that PraR dominantly represses reb expression. Furthermore, we found that the reb
      operon is highly expressed at low temperatures and that 2-oxoglutarate induces
      the expression of the reb operon by inhibiting PraR binding to the reb promoter.
      We conclude that R bodies are toxic not only in paramecium symbiosis but also in
      relationships between other bacteria and eukaryotic cells and that R-body
      formation is controlled by environmental factors.IMPORTANCECaedibacter species,
      which are obligate endosymbiotic bacteria of paramecia, produce R bodies, and R
      body-producing endosymbionts that are released from their hosts are pathogenic to
      symbiont-free paramecia. Besides Caedibacter species, R bodies have also been
      observed in a few free-living bacteria, but the significance of R-body production
      in these bacteria is still unknown. Recent advances in genome sequencing
      technologies revealed that many Gram-negative bacteria possess reb genes encoding
      R-body components, and interestingly, many of them are animal and plant
      pathogens. Azorhizobium caulinodans, a microsymbiont of the tropical legume
      Sesbania rostrata, also possesses reb genes. In this study, we demonstrate that
      A. caulinodans has ability to kill the host plant cells by producing R bodies,
      suggesting that pathogenicity conferred by an R body might be universal in
      bacteria possessing reb genes. Furthermore, we provide the first insight into the
      molecular mechanism underlying the expression of R-body production in response to
      environmental factors, such as temperature and 2-oxoglutarate.

PMID- 28743815
TI  - Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A
      Streptococcus.
AB  - Group A streptococcus (GAS) is an important human pathogen that causes a wide
      variety of cutaneous and systemic infections. Although originally thought to be
      an extracellular bacterium, numerous studies have demonstrated that GAS can
      trigger internalization into nonimmune cells to escape from immune surveillance
      or antibiotic-mediated killing. Epithelial cells possess a defense mechanism
      involving autophagy-mediated targeting and killing of GAS within lysosome-fused
      autophagosomes. In endothelial cells, in contrast, we previously showed that
      autophagy is not sufficient for GAS killing. In the present study, we showed
      higher galectin-3 (Gal-3) expression and lower Gal-8 expression in endothelial
      cells than in epithelial cells. The recruitment of Gal-3 to GAS is higher and the
      recruitment of Gal-8 to GAS is lower in endothelial cells than in epithelial
      cells. We further showed that Gal-3 promotes GAS replication and diminishes the
      recruitment of Gal-8 and ubiquitin, the latter of which is a critical protein for
      autophagy sequestration. After knockdown of Gal-3 in endothelial cells, the
      colocalization of Gal-8, parkin, and ubiquitin-decorated GAS is significantly
      increased, as is the interaction of Gal-8 and parkin, an E3 ligase. Furthermore,
      inhibition of Gal-8 in epithelial cells attenuates recruitment of parkin; both
      Gal-8 and parkin contribute to ubiquitin recruitment and GAS elimination. Animal
      studies confirmed that Gal-3-knockout mice develop less-severe skin damage and
      that GAS replication can be detected only in the air pouch and not in organs and
      endothelial cells. These results demonstrate that Gal-3 inhibits ubiquitin
      recruitment by blocking Gal-8 and parkin recruitment, resulting in GAS
      replication in endothelial cells.IMPORTANCE In epithelial cells, GAS can be
      efficiently killed within the lysosome-fused autophaosome compartment. However,
      we previously showed that, in spite of LC-3 recruitment, the autophagic machinery
      is not sufficient for GAS killing in endothelial cells. In this report, we
      provide the first evidence that Gal-3, highly expressed in endothelial cells,
      blocks the tagging of ubiquitin to GAS by inhibiting recruitment of Gal-8 and
      parkin, leading to an enhancement of GAS replication. We also provide the first
      demonstration that Gal-8 can interact with parkin, the critical E3 ligase, for
      resistance to intracellular bacteria by facilitating the decoration of bacteria
      with ubiquitin chains. Our findings reveal that differential levels of Gal-3 and
      Gal-8 expression and recruitment to GAS between epithelial cells and endothelial
      cells may contribute to the different outcomes of GAS elimination or survival and
      growth of GAS in these two types of cells.

PMID- 28743816
TI  - Penile Anaerobic Dysbiosis as a Risk Factor for HIV Infection.
AB  - Sexual transmission of HIV requires exposure to the virus and infection of
      activated mucosal immune cells, specifically CD4+ T cells or dendritic cells. The
      foreskin is a major site of viral entry in heterosexual transmission of HIV.
      Although the probability of acquiring HIV from a sexual encounter is low, the
      risk varies even after adjusting for known HIV risk factors. The genital
      microbiome may account for some of the variability in risk by interacting with
      the host immune system to trigger inflammatory responses that mediate the
      infection of mucosal immune cells. We conducted a case-control study of
      uncircumcised participants nested within a randomized-controlled trial of male
      circumcision in Rakai, Uganda. Using penile (coronal sulcus) swabs collected by
      study personnel at trial enrollment, we characterized the penile microbiome by
      sequencing and real-time PCR and cytokine levels by electrochemiluminescence
      assays. The absolute abundances of penile anaerobes at enrollment were associated
      with later risk of HIV seroconversion, with a 10-fold increase in Prevotella,
      Dialister, Finegoldia, and Peptoniphilus increasing the odds of HIV acquisition
      by 54 to 63%, after controlling for other known HIV risk factors. Increased
      abundances of anaerobic bacteria were also correlated with increased cytokines,
      including interleukin-8, which can trigger an inflammatory response that recruits
      susceptible immune cells, suggesting a mechanism underlying the increased risk.
      These same anaerobic genera can be shared between heterosexual partners and are
      associated with increased HIV acquisition in women, pointing to anaerobic
      dysbiosis in the genital microbiome and an accompanying inflammatory response as
      a novel, independent, and transmissible risk factor for HIV infection.IMPORTANCE
      We found that uncircumcised men who became infected by HIV during a 2-year
      clinical trial had higher levels of penile anaerobes than uncircumcised men who
      remained HIV negative. We also found that having higher levels of penile
      anaerobes was also associated with higher production of immune factors that
      recruit HIV target cells to the foreskin, suggesting that anaerobes may modify
      HIV risk by triggering inflammation. These anaerobes are known to be shared by
      heterosexual partners and are associated with HIV risk in women. Therefore,
      penile anaerobes may be a sexually transmissible risk factor for HIV, and
      modifying the penile microbiome could potentially reduce HIV acquisition in both
      men and women.

PMID- 28743818
TI  - AID-ing Signaling in Toxoplasma gondii.
AB  - The cyclic GMP-dependent protein kinase (PKG) of apicomplexan parasites is
      essential for secretion of micronemes and host cell invasion and egress. Both
      kinase specificity and localization can determine which substrates are
      phosphorylated. The functions of plasma membrane and cytosolic PKG isoforms of
      Toxoplasma gondii were unknown because of difficulties precisely manipulating
      expression of essential genes. Brown et al. (K. M. Brown, S. Long, and L. D.
      Sibley, mBio 8:e00375-17, https://doi.org/10.1128/mBio.00375-17) adapted the
      auxin-inducible degron (AID) system for conditional expression of T. gondii
      proteins. AID, in combination with clustered regularly interspaced short
      palindromic repeat (CRISPR)-Cas9 gene editing, facilitated creation of a panel of
      PKG mutants to demonstrate that the membrane association via acylation of PKG is
      critical for its essential functions in tachyzoites. The cytosolic form of PKG is
      not sufficient for viability and is dispensable. These studies illuminate a
      critical role for targeting of kinase complexes for parasite viability. The AID
      system enables rapid, conditional regulation of protein expression that expands
      the molecular toolbox of T. gondii.

PMID- 28743817
TI  - Bacterial Signaling Nucleotides Inhibit Yeast Cell Growth by Impacting
      Mitochondrial and Other Specifically Eukaryotic Functions.
AB  - We have engineered Saccharomyces cerevisiae to inducibly synthesize the
      prokaryotic signaling nucleotides cyclic di-GMP (cdiGMP), cdiAMP, and ppGpp in
      order to characterize the range of effects these nucleotides exert on eukaryotic
      cell function during bacterial pathogenesis. Synthetic genetic array (SGA) and
      transcriptome analyses indicated that, while these compounds elicit some common
      reactions in yeast, there are also complex and distinctive responses to each of
      the three nucleotides. All three are capable of inhibiting eukaryotic cell
      growth, with the guanine nucleotides exhibiting stronger effects than cdiAMP.
      Mutations compromising mitochondrial function and chromatin remodeling show
      negative epistatic interactions with all three nucleotides. In contrast, certain
      mutations that cause defects in chromatin modification and ribosomal protein
      function show positive epistasis, alleviating growth inhibition by at least two
      of the three nucleotides. Uniquely, cdiGMP is lethal both to cells growing by
      respiration on acetate and to obligately fermentative petite mutants. cdiGMP is
      also synthetically lethal with the ribonucleotide reductase (RNR) inhibitor
      hydroxyurea. Heterologous expression of the human ppGpp hydrolase Mesh1p
      prevented the accumulation of ppGpp in the engineered yeast and restored cell
      growth. Extensive in vivo interactions between bacterial signaling molecules and
      eukaryotic gene function occur, resulting in outcomes ranging from growth
      inhibition to death. cdiGMP functions through a mechanism that must be
      compensated by unhindered RNR activity or by functionally competent mitochondria.
      Mesh1p may be required for abrogating the damaging effects of ppGpp in human
      cells subjected to bacterial infection.IMPORTANCE During infections, pathogenic
      bacteria can release nucleotides into the cells of their eukaryotic hosts. These
      nucleotides are recognized as signals that contribute to the initiation of
      defensive immune responses that help the infected cells recover. Despite the
      importance of this process, the broader impact of bacterial nucleotides on the
      functioning of eukaryotic cells remains poorly defined. To address this, we
      genetically modified cells of the eukaryote Saccharomyces cerevisiae (baker's
      yeast) to produce three of these molecules (cdiAMP, cdiGMP, and ppGpp) and used
      the engineered strains as model systems to characterize the effects of the
      molecules on the cells. In addition to demonstrating that the nucleotides are
      each capable of adversely affecting yeast cell function and growth, we also
      identified the cellular functions important for mitigating the damage caused,
      suggesting possible modes of action. This study expands our understanding of the
      molecular interactions that can take place between bacterial and eukaryotic
      cells.

PMID- 28743819
TI  - Positive Autoregulation of an Acyl-Homoserine Lactone Quorum-Sensing Circuit
      Synchronizes the Population Response.
AB  - Many proteobacteria utilize acyl-homoserine lactone quorum-sensing signals. At
      low population densities, cells produce a basal level of signal, and when
      sufficient signal has accumulated in the surrounding environment, it binds to its
      receptor, and quorum-sensing-dependent genes can be activated. A common
      characteristic of acyl-homoserine lactone quorum sensing is that signal
      production is positively autoregulated. We have examined the role of positive
      signal autoregulation in Pseudomonas aeruginosa We compared population responses
      and individual cell responses in populations of wild-type P. aeruginosa to
      responses in a strain with the signal synthase gene controlled by an arabinose
      inducible promoter so that signal was produced at a constant rate per cell
      regardless of cell population density. At a population level, responses of the
      wild type and the engineered strain were indistinguishable, but the responses of
      individual cells in a population of the wild type showed greater synchrony than
      the responses of the engineered strain. Although sufficient signal is required to
      activate expression of quorum-sensing-regulated genes, it is not sufficient for
      activation of certain genes, the late genes, and their expression is delayed
      until other conditions are met. We found that late gene responses were reduced in
      the engineered strain. We conclude that positive signal autoregulation is not a
      required element in acyl-homoserine lactone quorum sensing, but it functions to
      enhance synchrony of the responses of individuals in a population. Synchrony
      might be advantageous in some situations, whereas a less coordinated quorum
      sensing response might allow bet hedging and be advantageous in other
      situations.IMPORTANCE There are many quorum-sensing systems that involve a
      transcriptional activator, which responds to an acyl-homoserine lactone signal.
      In all of the examples studied, the gene coding for signal production is
      positively autoregulated by the signal, and it has even been described as
      essential for a quorum-sensing response. We have used the opportunistic pathogen
      Pseudomonas aeruginosa as a model to show that positive autoregulation is not
      required for a robust quorum-sensing response. We also show that positive
      autoregulation of signal production enhances the synchrony of the response. This
      information enhances our general understanding of the biological significance of
      how acyl-homoserine lactone quorum-sensing circuits are arranged.

PMID- 28743820
TI  - The effects of Suramin on Ca2+ activated force and sarcoplasmic reticulum Ca2+
      release in skinned fast-twitch skeletal muscle fibers of the rat.
AB  - Suramin has long been used in the treatment of various human diseases.
      Intravenous infusions of Suramin are commonly administered to patients over
      extended periods of time but there are a number of significant contraindications
      with peripheral muscle weakness being one of the most frequently reported.
      Previous work has shown that even after a single infusion (300 mg kg-1) Suramin
      remains in skeletal muscle in effective concentrations (11.6 MUg mL-1; 84 days)
      for prolonged periods. These observations provide a strong rationale for
      investigation of the specific effects of Suramin on skeletal muscle function.
      Single mechanically skinned fibers were directly exposed to Suramin (10, 100 or
      500 MUmol L-1) for defined durations (2-10 min) in controlled physiological
      solutions that mimic the intracellular ionic environment of a fiber. Suramin
      treatment (10-500 MUmol L-1) directly affected the contractile apparatus in a
      dose-dependent manner causing a decrease in Ca2+-sensitivity (pCa50 = -log (Ca2+)
      concentration, where 50% of maximum Ca2+- activated force is produced) by 0.14 to
      0.42 pCa units and reduction in maximum Ca2+-activated force by 14 to 62%.
      Suramin treatment (100 MUmol L-1 for 10 min and 500 MUmol L-1 for 2 min) also
      caused development of a Ca2+-independent force corresponding to 2.89 +/- 4.33 and
      16.77 +/- 7.50% of pretreatment maximum Ca2+-activated force, respectively.
      Suramin treatment (100 MUmol L-1, 2 min) also increased the rate of sarcoplasmic
      reticulum (SR) Ca2+ release without significant changes in SR Ca2+ uptake. We
      report new functional effects for Suramin related to alterations in both the
      contractile apparatus and SR Ca2+-handling of skeletal muscle that may contribute
      to the peripheral muscle weakness noted in human pharmacological treatments.

PMID- 28743821
TI  - The effect of dietary nitrate supplementation on the spatial heterogeneity of
      quadriceps deoxygenation during heavy-intensity cycling.
AB  - This study investigated the influence of dietary inorganic nitrate (NO3-)
      supplementation on pulmonary O2 uptake (VO2) and muscle deoxyhemoglobin/myoglobin
      (i.e. deoxy [Hb + Mb]) kinetics during submaximal cycling exercise. In a
      randomized, placebo-controlled, cross-over study, eight healthy and physically
      active male subjects completed two step cycle tests at a work rate equivalent to
      50% of the difference between the gas exchange threshold and peak VO2 over
      separate 4-day supplementation periods with NO3--rich (BR; providing 8.4 mmol NO3
      ?day-1) and NO3--depleted (placebo; PLA) beetroot juice. Pulmonary VO2 was
      measured breath-by-breath and time-resolved near-infrared spectroscopy was
      utilized to quantify absolute deoxy [Hb + Mb] and total [Hb + Mb] within the
      rectus femoris, vastus lateralis, and vastus medialis There were no significant
      differences (P > 0.05) in the primary deoxy [Hb + Mb] mean response time or
      amplitude between the PLA and BR trials at each muscle site. BR significantly
      increased the mean (three-site) end-exercise deoxy [Hb + Mb] (PLA: 91 +/- 9 vs.
      BR: 95 +/- 12 MUmol/L, P < 0.05), with a tendency to increase the mean (three
      site) area under the curve for total [Hb + Mb] responses (PLA: 3650 +/- 1188 vs.
      BR: 4467 +/- 1315 MUmol/L sec-1, P = 0.08). The VO2 slow component reduction
      after BR supplementation (PLA: 0.27 +/- 0.07 vs. BR: 0.23 +/- 0.08 L min-1, P =
      0.07) correlated inversely with the mean increases in deoxy [Hb + Mb] and total
      [Hb + Mb] across the three muscle regions (r2 = 0.62 and 0.66, P < 0.05). Dietary
      NO3- supplementation increased O2 diffusive conductance across locomotor muscles
      in association with improved VO2 dynamics during heavy-intensity cycling
      transitions.

PMID- 28743822
TI  - Bronchial microdialysis monitoring of inflammatory response in open abdominal
      aortic aneurysm repair; an observational study.
AB  - Aortic surgery results in ischemia-reperfusion injury that induces an
      inflammatory response and frequent complications. The magnitude of the
      inflammatory response in blood and bronchi may be associated with the risk of
      immediate complications. The purpose of the study was to evaluate bronchial
      microdialysis as a continuous monitoring of cytokines in bronchial epithelial
      lining fluid (ELF) and to determine whether bronchial ELF cytokine levels reflect
      the ischemia-reperfusion injury and risk for complications during open abdominal
      aortic aneurysm (AAA) repair. We measured cytokines in venous blood using
      microdialysis and in serum for comparison. Sixteen patients scheduled for
      elective open AAA repair were included in a prospective observational study.
      Microdialysis catheters were introduced into a bronchi and a cubital vein.
      Eighteen cytokines were measured using a Bio-Plex Magnetic Human Cytokine Panel.
      Samples were collected before and during cross-clamping of the aorta as well as
      from 0 to 60 min and from 60 to 120 min of reperfusion. The ELF levels of several
      cytokines changed significantly during reperfusion. In particular, IL-6 increased
      more than 10-fold and IL-13 more than 5-fold during ischemia and reperfusion.
      Also, the venous levels of several inflammatory and anti-inflammatory cytokines
      increased and exhibited their highest concentration during reperfusion. Both
      bronchial and venous cytokine levels correlated with duration of the procedure,
      intensive care days, and preoperative kidney disease. Three patients suffered
      organ failure as a direct consequence of the procedure, and in these patients the
      bronchial ELF concentrations of 17 of 18 cytokines differed significantly from
      patients without such complications. Bronchial microdialysis is suited for
      continuous monitoring of inflammation during open AAA repair. The bronchial ELF
      cytokine levels may be useful in predicting immediate complications such as organ
      failure in patients undergoing vascular surgery.

PMID- 28743823
TI  - Unloading-induced atrophy and decreased oxidative capacity of the soleus muscle
      in rats are reversed by pre- and postconditioning with mild hyperbaric oxygen.
AB  - Our aim was to determine the effects of pre- and/or postconditioning with mild
      hyperbaric oxygen (1.25 atmospheric pressure, 36% oxygen for 3 h/day) on the
      properties of the soleus muscle that was atrophied by hindlimb suspension-induced
      unloading. Twelve groups of 8-week-old rats were housed under normobaric
      conditions (1 atmospheric pressure, 20.9% oxygen) or exposed to mild hyperbaric
      oxygen for 2 weeks. Ten groups then were housed under normobaric conditions for 2
      weeks with their hindlimbs either unloaded via suspension or not unloaded. Six
      groups subsequently were either housed under normobaric conditions or exposed to
      mild hyperbaric oxygen for 2 weeks: the suspended groups were allowed to recover
      under reloaded conditions (unrestricted normal cage activity). Muscle weights,
      cross-sectional areas of all fiber types, oxidative capacity (muscle succinate
      dehydrogenase activity and fiber succinate dehydrogenase staining intensity)
      decreased, and a shift of fibers from type I to type IIA and type IIC was
      observed after hindlimb unloading. In addition, mRNA levels of peroxisome
      proliferator-activated receptor gamma coactivator-1alpha decreased, whereas those
      of forkhead box-containing protein O1 increased after hindlimb unloading. Muscle
      atrophy and decreased oxidative capacity were unaffected by either pre- or
      postconditioning with mild hyperbaric oxygen. In contrast, these changes were
      followed by a return to nearly normal levels after 2 weeks of reloading when pre-
      and postconditioning were combined. Therefore, a combination of pre- and
      postconditioning with mild hyperbaric oxygen can be effective against the atrophy
      and decreased oxidative capacity of skeletal muscles associated with hindlimb
      unloading.

PMID- 28743824
TI  - Margaret McCartney: Charities should respect evidence.

PMID- 28743826
TI  - News Feature: Can animal culture drive evolution?

PMID- 28743841
TI  - Double Fano resonances in individual metallic nanostructure for high sensing
      sensitivity.
AB  - In this paper, we report the design and observation of double Fano resonances
      (DFRs) in an individual symmetry reduced nanostructure and the induced high
      sensing sensitivity. Such a plasmonic nanostructure consists of a partially
      overlapped double metallic nanotriangles with unequal sizes fabricated by using
      the fast and low-cost angle-resolved nanosphere lithography. Symmetry breaking
      generates two narrow quadrupolar dark modes, which further enhance the coupling
      with fundamental bright dipole modes within the same structure, manifesting the
      effect of DFRs. The resonance wavelength and line shape of DFRs can be tailored
      by changing the degree of asymmetry as well as the size of the designed
      nanostructure. Based on DFRs, a high sensitivity to dielectric environment with a
      maximum figure of merit of 35 is measured. Due to fast manufacturing process with
      high reproducibility and high structural tunability, the fabricated individual
      metallic nanostructure provides an opportunity to significant potential
      applications in localized surface plasmon resonance (LSPR) based single or double
      wavelength sensors in the near-infrared region.

PMID- 28743825
TI  - Contribution of the clathrin adaptor AP-1 subunit u1 to acidic cluster protein
      sorting.
AB  - Acidic clusters act as sorting signals for packaging cargo into clathrin-coated
      vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. To
      find acidic cluster sorting machinery, we performed a gene-trap screen and
      identified the medium subunit (u1) of the clathrin adaptor AP-1 as a top hit. In
      u1 knockout cells, intracellular CCVs still form, but acidic cluster proteins are
      depleted, although several other CCV components were either unaffected or
      increased, indicating that cells can compensate for long-term loss of AP-1. In
      vitro experiments showed that the basic patch on u1 that interacts with the Nef
      acidic cluster also contributes to the binding of endogenous acidic cluster
      proteins. Surprisingly, u1 mutant proteins lacking the basic patch and/or the
      tyrosine-based motif binding pocket could rescue the u1 knockout phenotype
      completely. In contrast, these mutants failed to rescue Nef-induced down
      regulation of MHC class I, suggesting a possible mechanism for attacking the
      virus while sparing the host cell.

PMID- 28743842
TI  - [New methods for the evaluation of bone quality. The importance of assessing bone
      quality.]
AB  - Fracture risk in patients with secondary osteoporosis, which includes
      glucocorticoid-induced osteoporosis, was found to be higher than the fracture
      risk predicted by decreased bone mineral density. Moreover, a large scale
      randomized clinical study also found that an increased bone mineral density was
      not a strong predictor of the effectiveness of anti-resorptive agents in
      preventing fractures. The accumulation of such evidence has led us to conclude
      that an explanatory factor of bone strength other than bone mineral density must
      be bone quality. The development of a new method for assessment of bone quality
      is imperative to more efficiently i)identify patients at high risk of fracture,
      ii)determine drug selection and assess drug effectiveness, and iii)decide on drug
      continuation, discontinuation, or changes.

PMID- 28743843
TI  - [New methods for the evaluation of bone quality. How does decay bone quality?]
AB  - The degree of mineralization and microstructure are regulated by bone turnover.
      Bone collagen enzymatic cross-links and advanced glycation end products(AGEs)are
      affected by various factors such as the levels of oxidative stress and glycation
      as well as tissue lifespan. Deterioration of bone material properties markedly
      advances due to increases in oxidative stress, glycation stress, reactive oxygen
      species, carbonyl stress associated with aging and reduced sex hormone levels,
      and glucocorticoid use. In this review, we described determinants of bone quality
      and strength.

PMID- 28743844
TI  - [New methods for the evaluation of bone quality. Assessment of bone structural
      property using imaging.]
AB  - Structural property of bone includes micro- or nano-structural property of the
      trabecular and cortical bone, and macroscopic geometry. Radiological technique is
      useful to analyze the bone structural property;multi-detector row CT(MDCT)or high
      resolution peripheral QCT(HR-pQCT)is available to analyze human bone in vivo. For
      the analysis of hip geometry, CT-based hip structure analysis(HSA)is available as
      well as DXA-based HSA. These structural parameters are related to biomechanical
      property, and these assessment tools provide information of pathological changes
      or the effects of anti-osteoporotic agents on bone.

PMID- 28743845
TI  - [New methods for the evaluation of bone quality. Diseases Affecting Bone
      Quality.]
AB  - Impaired bone quality is associated with fragility bone fractures independently
      of bone mineral density. Lifestyle disease-induced osteoporosis, such as diabetes
      or chronic kidney disease, and glucocorticoid-induced osteoporosis are listed as
      the diseases affecting bone quality. TBS(trabecular bone score)developed recently
      will be able to evaluate the trabecular microarchitecture quickly and easily.
      Various clinical studies evaluated bone quality by TBS has performed. I give an
      outline about the diseases affecting bone quality.

PMID- 28743846
TI  - [New methods for the evaluation of bone quality. Bone quality evaluation by QCT.]
AB  - In osteoporosis, the risk of fracture is influenced by decrease of bone mineral
      density and deterioration of bone quality. The latter includes deterioration of
      the material and structural properties of bone. These changes arise from the
      influence of changes in hormonal balance, aging, changes in mechanical stress,
      lifestyle-related diseases, etc. on bone absorption and bone formation as the
      coupled functions of osteoclasts and osteoblasts. Deterioration of bone quality
      occurs at various levels ranging from the molecular to the tissue level, or even
      at the individual level, and leads to an increased fracture risk. In this
      chapter, bone quality evaluation using quantitative computed tomography is
      discussed among evaluation methods of various fracture risk.

PMID- 28743847
TI  - [New methods for the evaluation of bone quality. Bone Quality Evaluation by QUS.]
AB  - The conventional ultrasonic bone densitometry systems(quantitative
      ultrasound:QUS)are now popular for the initial screening of osteoporosis. These
      systems can give us velocity(SOS)and broadband attenuation(BUA)of ultrasonic
      waves, which propagated in the heel. This paper describes the physical meaning of
      these parameters and introduces the idea of standardization, s-SOS and s-BUA. In
      addition, new QUS techniques for the further investigation of bone quality are
      also introduced. These techniques, two wave phenomenon and Axial
      Transmission(AT)can induce the individual properties of cortical and cancellous
      bones by the ultrasonic measurements.

PMID- 28743848
TI  - [New methods for the evaluation of bone quality. Assessments of bone quality from
      bone tissues.]
AB  - Indeed DXA and quantitative CT both which measure bone mineral amount are well
      established methods to predict bone volume, but some clinical studies say that
      different rates of bone turnover can cause discrepancies between bone mineral
      density and bone volume. Bone strength is accused to not only bone mineral
      density but bone quality, and developments of the osteoporosis drugs have made
      "bone quality" more important in explaining bone strength. Bone quality refers to
      architecture, turnover, damage accumulation and mineralization. Turnover and
      microdamage at bone tissue are evaluated only by bone histomorphometry, with
      which it becomes possible to assess bone quality from bone tissue combination
      with micro-CT and vibrational spectroscopy.

PMID- 28743849
TI  - [New methods for the evaluation of bone quality. Assessment of bone quality by HR
      pQCT.]
AB  - Bone microstructure is one of the important factors for defining bone quality.
      High Resolution peripheral Quantitative CT(HR-pQCT)enables us to evaluate bone
      microstructure in patients with osteoporosis noninvasively. It is applied to
      fracture risk assessment, analysis for pathogenesis of osteoporosis, and study of
      effects of osteoporosis drugs.

PMID- 28743850
TI  - [New methods for the evaluation of bone quality. Nanoindentation protocol for
      measurement of bone mechanical properties of material level.]
AB  - Bone is an inhomogeneous, anisotropic natural biomaterial with complex,
      multiscale structural variations. Thus, experiments on the bulk scale using a
      universal testing machine are not applicable for localized precision mechanical
      testing of bone. Nanoscale mechanical testing technologies such as
      nanoindentation enables to assess the intrinsic toughening mechanism of bone,
      which is a function of the highly-organized matrix proteins within the
      mineralized nanostructure. Understanding the basic nanomechanical properties of
      calcified tissues will help us to appreciate general concepts associated with the
      excellent design of advanced engineering materials and engineered tissues.

PMID- 28743851
TI  - [New methods for the evaluation of bone quality. DXA-based analysis of bone
      quality:trabecular bone score(TBS).]
AB  - Trabecular bone score(TBS)is a texture measure that evaluates pixel gray-level
      variations in lumbar spine DXA images, and provides skeletal information distinct
      from the standard BMD measurement. Recent clinical evidences show that TBS is
      associated with fracture risk in primary and secondary osteoporosis, and can be
      used together with FRAXR and BMD to adjust FRAX-probability of fracture in
      postmenopausal women and older men. However, athough treatment-related increases
      are reflected in the TBS, these are considerably smaller than the changes in BMD
      and there is insufficient evidence that TBS can be used to assess response to
      pharmacologic treatment.

PMID- 28743852
TI  - [New methods for the evaluation of bone quality. Bone Quality Marker.]
AB  - In recent years, undercarboxylated osteocalcin(ucOC), advanced glycation
      endproducts(AGEs)and homocysteine are attracting attention as factors defining
      bone strength. However, there are still many problems in its measurement, and it
      has not yet been routinely used in clinical practice. If solving the problem in
      the future, it is expected that the utility on bone quality will also increase.

PMID- 28743853
TI  - [New methods for the evaluation of bone quality. Relationship between bone
      resorption inhibitors and bony quality.]
AB  - Bone resorption inhibitors used in Japan are bisphosphonate, selective estrogen
      receptor modulators(SERMs), denosumab, eldecalcitol, and calcitonin. The
      structural and material properties of bone quality are important factors in
      osteoporosis treatment. In contrast to improvements in bone density, those in
      bone quality are difficult to clinically determine as no simple test is available
      and changes are difficult to detect. Numerous reports have been published on the
      mechanisms by which bone resorption inhibitors increase bone density and suppress
      bone fractures. This paper describes the effects of each bone resorption
      inhibitor and focusses on burr holes, trabeculae, microdamage, collagen cross
      links, and microstructures.

PMID- 28743854
TI  - [New methods for the evaluation of bone quality. Bone anabolic agents and bone
      quality.]
AB  - Teriparatide(TPTD)products that can be used clinically in Japan include a daily
      subcutaneous injection form produced by genetic engineering and a weekly
      subcutaneous injectable TPTD acetate form produced by chemical synthesis.
      Published reports indicate that both forms exhibit excellent antifracture
      efficacy, and as the only anabolic agents that promote osteogenesis, TPTD
      products now occupy a prominent position. However, the two forms differ
      considerably, not only in frequency of administration, but also in mechanism of
      action. The daily form stimulates osteogenesis and accompanying resorption
      through more radical high bone turnover, and early in the course of treatment,
      intracortical porosity and apatite crystallization decrease, while immature
      collagen crosslinking increases. However, because daily formulations also produce
      an increase in cortical surface area or cortical thickness, the effects are
      counterbalanced, and bone strength is maintained. In contrast, the weekly form
      prioritizes osteogenesis, and by concurrently lowering turnover below
      pretreatment levels, improves trabecular bone mass and structure, and enhances
      strength without leading to cortical porosity and other undesirable phenomena.
      Abaloparatide, a PTHrP(1-34)analog that is homologous with the biologically
      active site of PTH drugs, is currently under development, and we eagerly
      anticipate further clarification of the mechanism of action of each formulation
      on bone.

PMID- 28743855
TI  - Evaluation of an undergraduate occupational health program in Iran based on
      alumni perceptions: a structural equation model.
AB  - PURPOSE: Evaluating educational programs can improve the quality of education.
      The present study evaluated the undergraduate occupational health program at the
      Semnan University of Medical Sciences in Semnan, Iran, with a focus on the
      associations between alumni perceptions of the learning environment and the
      outcomes of the occupational health program. METHODS: A cross-sectional
      questionnaire survey was conducted among alumni of the undergraduate occupational
      health program. We asked alumni to rate their perceptions of the items using a 4
      point Likert scale. The associations between alumni perceptions of the
      educational program and curriculum, faculty, institutional resources, and
      learning outcomes were modeled and described using structural equation modeling
      procedures. RESULTS: A descriptive analysis of alumni perceptions indicated low
      evaluations for the administrative system, practical and research-based courses,
      and the number of faculty members. We found that a structural model of the
      evaluation variables of curriculum, faculty qualifications, and institutional
      resources significantly predicted undergraduate educational outcomes. The
      curriculum had direct and indirect effects on learning outcomes, mediated by
      faculty. CONCLUSION: The findings of our study highlight the usefulness of the
      structural equation modeling approach for examining links between variables
      related to the learning process and learning outcomes. Surveys of alumni can
      provide data for reassessing the learning environment in the light of the
      professional competencies needed for occupational health graduates.

PMID- 28743856
TI  - Kaposi Sarcoma in an Human Immunodeficiency Virus (HIV)-Seronegative
      Mediterranean Female: Report of a Rare Case.
AB  - BACKGROUND Kaposi sarcoma is a malignancy commonly linked to HIV infection or
      immunosuppression. An association with human herpes virus 8 (HHV-8) infection has
      also been reported. We present a case of classic Kaposi sarcoma in a female
      Mediterranean patient. CASE REPORT A 57-year-old white female of Greek ethnicity,
      with no history of HIV infection or immunosuppression, presented to the Surgical
      Out-patient Department of our Center, with complaints of extensive discolored
      skin lesion on both legs, initially considered as chronic vein insufficiency.
      Histopathological findings from skin biopsies revealed Kaposi sarcoma.
      CONCLUSIONS Non-HIV-related Kaposi sarcoma is an HHV-8-related,
      angioproliferating skin cancer that can cause pain, disfigurement, and limb
      dysfunction. High suspicion of this condition can lead to early treatment and
      delay progression.

PMID- 28743857
TI  - The Clinical Signification of Claudin-11 Promoter Hypermethylation for Laryngeal
      Squamous Cell Carcinoma.
AB  - BACKGROUND Claudin-11 (CLDN11) is frequently silenced by its promoter
      hypermethylation. Previous studies have shown that CLDN11 promoter
      hypermethylation is a potential biomarker for diagnosing various cancers. The aim
      of this study was to investigate CLDN11 promoter methylation and its potential
      relevance to clinicopathologic features and prognosis of patients with laryngeal
      squamous cell carcinoma (LSCC). MATERIAL AND METHODS Using the quantitative
      methylation-specific polymerase chain reaction (qMSP), CLDN11 promoter
      methylation was measured in 91 tumor tissues and their paired adjacent normal
      tissues, and the relationship between CLDN11 methylation and clinicopathologic
      features was evaluated. A receiver operating characteristic (ROC) curve was
      created to assess diagnostic values, and the Kaplan-Meier survival analysis was
      used to evaluate the association between CLDN11 methylation and prognosis of
      patients with LSCC. RESULTS Our results showed significantly elevated promoter
      methylation of CLDN11 in tumor tissues compared to their adjacent tissues
      (p=1.227E-16). CLDN11 promoter methylation also increased in patients with lymph
      node metastasis (p=0.009), advanced clinical stage (p=9.26E-06) and higher T
      classification (p=0.003). The area under the ROC curve (AUC) of CLDN11 was 0.884
      (95% CI=0.835-0.932, p<0.01). The Kaplan-Meier analysis indicated that high
      CLDN11 promoter methylation levels were associated with poor overall survival of
      LSCC patients (log-rank test, p=0.007). CONCLUSIONS We demonstrated that CLDN11
      promoter hypermethylation is a frequent event in LSCC, and contributes to
      metastasis and progression of LSCC. Thus, CLDN11 could be a potential biomarker
      for diagnosis and prognosis of LSCC patients.

PMID- 28743858
TI  - Triggerable tough hydrogels for gastric resident dosage forms.
AB  - Systems capable of residing for prolonged periods of time in the gastric cavity
      have transformed our ability to diagnose and treat patients. Gastric resident
      systems for drug delivery, ideally need to be: ingestible, be able to change
      shape or swell to ensure prolonged gastric residence, have the mechanical
      integrity to withstand the forces associated with gastrointestinal motility, be
      triggerable to address any side effects, and be drug loadable and release drug
      over a prolonged period of time. Materials that have been primarily utilized for
      these applications have been largely restricted to thermoplastics and thermosets.
      Here we describe a novel set of materials, triggerable tough hydrogels, meeting
      all these requirement, supported by evaluation in a large animal model and
      ultimately demonstrate the potential of triggerable tough hydrogels to serve as
      prolonged gastric resident drug depots. Triggerable tough hydrogels may be
      applied in myriad of applications, including bariatric interventions, drug
      delivery, and tissue engineering.The use of drug delivery systems for the
      gastrointestinal tract has been faced with a number of drawbacks related to their
      prolonged use. Here, the authors develop a drug-loaded hydrogel with high
      strength to withstand long-term gastrointestinal motility and can be triggered to
      dissolve on demand.

PMID- 28743859
TI  - Let-7 microRNA-dependent control of leukotriene signaling regulates the
      transition of hematopoietic niche in mice.
AB  - Hematopoietic stem and progenitor cells arise from the vascular endothelium of
      the dorsal aorta and subsequently switch niche to the fetal liver through unknown
      mechanisms. Here we report that vascular endothelium-specific deletion of mouse
      Drosha (Drosha cKO), an enzyme essential for microRNA biogenesis, leads to anemia
      and death. A similar number of hematopoietic stem and progenitor cells emerge
      from Drosha-deficient and control vascular endothelium, but Drosha cKO-derived
      hematopoietic stem and progenitor cells accumulate in the dorsal aorta and fail
      to colonize the fetal liver. Depletion of the let-7 family of microRNAs is a
      primary cause of this defect, as it leads to activation of leukotriene B4
      signaling and induction of the alpha4beta1 integrin cell adhesion complex in
      hematopoietic stem and progenitor cells. Inhibition of leukotriene B4 or integrin
      rescues maturation and migration of Drosha cKO hematopoietic stem and progenitor
      cells to the fetal liver, while it hampers hematopoiesis in wild-type animals.
      Our study uncovers a previously undefined role of innate leukotriene B4 signaling
      as a gatekeeper of the hematopoietic niche transition.Hematopoietic stem and
      progenitor cells are generated first from the vascular endothelium of the dorsal
      aorta and then the fetal liver but what regulates this switch is unknown. Here,
      the authors show that changing miRNA biogenesis and leukotriene B4 signaling in
      mice modulates this switch in the niche.

PMID- 28743860
TI  - Bivariate genome-wide association meta-analysis of pediatric musculoskeletal
      traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus.
AB  - Bone mineral density is known to be a heritable, polygenic trait whereas genetic
      variants contributing to lean mass variation remain largely unknown. We estimated
      the shared SNP heritability and performed a bivariate GWAS meta-analysis of total
      body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD)
      regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34
      52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic
      component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects
      in eight loci, including seven established bone mineral density loci: WNT4,
      GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the
      TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a
      stronger association with the former trait. We show that SREBF1 is expressed in
      murine and human osteoblasts, as well as in human muscle tissue. This is the
      first bivariate GWAS meta-analysis to demonstrate genetic factors with
      pleiotropic effects on bone mineral density and lean mass.Bone mineral density
      and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues
      perform bivariate GWAS analyses of total body lean mass and bone mass density in
      children, and show genetic loci with pleiotropic effects on both traits.

PMID- 28743861
TI  - Multimodal Fingerprints of Resting State Networks as assessed by Simultaneous
      Trimodal MR-PET-EEG Imaging.
AB  - Simultaneous MR-PET-EEG (magnetic resonance imaging - positron emission
      tomography - electroencephalography), a new tool for the investigation of
      neuronal networks in the human brain, is presented here for the first time. It
      enables the assessment of molecular metabolic information with high spatial and
      temporal resolution in a given brain simultaneously. Here, we characterize the
      brain's default mode network (DMN) in healthy male subjects using multimodal
      fingerprinting by quantifying energy metabolism via 2- [18F]fluoro-2-desoxy-D
      glucose PET (FDG-PET), the inhibition - excitation balance of neuronal activation
      via magnetic resonance spectroscopy (MRS), its functional connectivity via fMRI
      and its electrophysiological signature via EEG. The trimodal approach reveals a
      complementary fingerprint. Neuronal activation within the DMN as assessed with
      fMRI is positively correlated with the mean standard uptake value of FDG.
      Electrical source localization of EEG signals shows a significant difference
      between the dorsal DMN and sensorimotor network in the frequency range of delta,
      theta, alpha and beta-1, but not with beta-2 and beta-3. In addition to basic
      neuroscience questions addressing neurovascular-metabolic coupling, this new
      methodology lays the foundation for individual physiological and pathological
      fingerprints for a wide research field addressing healthy aging, gender effects,
      plasticity and different psychiatric and neurological diseases.

PMID- 28743862
TI  - Co-option of the cardiac transcription factor Nkx2.5 during development of the
      emu wing.
AB  - The ratites are a distinctive clade of flightless birds, typified by the emu and
      ostrich that have acquired a range of unique anatomical characteristics since
      diverging from basal Aves at least 100 million years ago. The emu possesses a
      vestigial wing with a single digit and greatly reduced forelimb musculature.
      However, the embryological basis of wing reduction and other anatomical changes
      associated with loss of flight are unclear. Here we report a previously unknown
      co-option of the cardiac transcription factor Nkx2.5 to the forelimb in the emu
      embryo, but not in ostrich, or chicken and zebra finch, which have fully
      developed wings. Nkx2.5 is expressed in emu limb bud mesenchyme and maturing wing
      muscle, and mis-expression of Nkx2.5 throughout the limb bud in chick results in
      wing reductions. We propose that Nkx2.5 functions to inhibit early limb bud
      expansion and later muscle growth during development of the vestigial emu
      wing.The transcription factor Nkx2.5 is essential for heart development. Here,
      the authors identify a previously unknown expression domain for Nkx2.5 in the emu
      wing and explore its role in diminished wing bud development in the flightless
      emu, compared with three other birds that have functional wings.

PMID- 28743863
TI  - Transcriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a
      Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle.
AB  - Interactions between tumor cells and tumor microenvironment are considered
      critical in carcinogenesis, tumor invasion and metastasis. To examine
      transcriptome changes and to explore the relationship with tumor microenvironment
      in canine cutaneous melanocytoma and melanoma, we extracted RNA from formalin
      fixed, paraffin-embedded (FFPE) specimens and analyzed them by means of RNA-seq
      for transcriptional analysis. Melanocytoma and melanoma samples were compared to
      detect differential gene expressions and significant enriched pathways were
      explored to reveal functional relations between differentially expressed genes.
      The study demonstrated a differential expression of 60 genes in melanomas
      compared to melanocytomas. The differentially expressed genes cluster in the
      extracellular matrix-receptor interaction, protein digestion and absorption,
      focal adhesion and PI3K-Akt (phosphoinositide 3-kinase/protein kinase B)
      signaling pathways. Genes encoding for several collagen proteins were more
      commonly differentially expressed. Results of the RNA-seq were validated by qRT
      PCR and protein expression of some target molecules was investigated by means of
      immunohistochemistry. We hypothesize that the developing melanoma actively
      promotes collagen metabolism and extracellular matrix remodeling as well as
      enhancing cell proliferation and survival contributing to disease progression and
      metastasis. In this study, we also detected unidentified genes in human melanoma
      expression studies and uncover new candidate drug targets for further testing in
      canine melanoma.

PMID- 28743864
TI  - Optical Band Gap Alteration of Graphene Oxide via Ozone Treatment.
AB  - Graphene oxide (GO) is a graphene derivative that emits fluorescence, which makes
      GO an attractive material for optoelectronics and biotechnology. In this work, we
      utilize ozone treatment to controllably tune the band gap of GO, which can
      significantly enhance its applications. Ozone treatment in aqueous GO suspensions
      yields the addition/rearrangement of oxygen-containing functional groups
      suggested by the increase in vibrational transitions of C-O and C=O moieties.
      Concomitantly it leads to an initial increase in GO fluorescence intensity and
      significant (100 nm) blue shifts in emission maxima. Based on the model of GO
      fluorescence originating from sp2 graphitic islands confined by oxygenated
      addends, we propose that ozone-induced functionalization decreases the size of
      graphitic islands affecting the GO band gap and emission energies. TEM analyses
      of GO flakes confirm the size decrease of ordered sp2 domains with ozone
      treatment, whereas semi-empirical PM3 calculations on model addend-confined
      graphitic clusters predict the inverse dependence of the band gap energies on sp2
      cluster size. This mod el explains ozone-induced increase in emission energies
      yielding fluorescence blue shifts and helps develop an understanding of the
      origins of GO fluorescence emission. Furthermore, ozone treatment provides a
      versatile approach to controllably alter GO band gap for optoelectronics and bio
      sensing applications.

PMID- 28743865
TI  - Functional relationship between material property, applied frequency and ozone
      generation for surface dielectric barrier discharges in atmospheric air.
AB  - We report the experimental characterization of ozone generation in dielectric
      barrier discharges as a function of the material and characteristics of the
      dielectric barrier, operating frequency and the power consumed by a surface DBD
      plasma reactor in air at atmospheric pressure. To identify the effect of the
      dielectric barrier, ozone production curves corresponding to ten dielectric
      barriers with different effective thicknesses and thermal properties are compared
      and analyzed for two combinations of voltage amplitudes and frequencies: 7 kV/10
      kHz and 8.5 kV/14 kHz. The influence of the operating frequency over the ozone
      generated by a DBD-plasma reactor is studied by varying the frequency in the
      range 8-20 kHz. The correlation between power measurements and ozone
      concentrations as well as ozone quenching effects at extreme power conditions are
      also discussed.

PMID- 28743866
TI  - Mass Spectrometry Imaging proves differential absorption profiles of well
      characterised permeability markers along the crypt-villus axis.
AB  - Knowledge about the region-specific absorption profiles from the gastrointestinal
      tract of orally administered drugs is a critical factor guiding dosage form
      selection in drug development. We have used a novel approach to study three well
      characterized permeability and absorption marker drugs in the intestine.
      Propranolol and metoprolol (highly permeable compounds) and atenolol (low
      moderate permeability compound) were orally co-administered to rats. The site of
      drug absorption was revealed by high spatial resolution matrix-assisted laser
      desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by
      quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI
      identified endogenous molecular markers that illustrated the villi structures and
      confirmed the different absorption sites assigned to histological landmarks for
      the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter
      transit distance in contrast to atenolol, which was absorbed more slowly from
      more distal sites. This study provides novel insights into site specific
      absorption for each of the compounds along the crypt-villus axis, as well as
      confirming a proximal-distal absorption gradient along the intestine. The
      combined analytical approach allowed the quantification and spatial resolution of
      drug distribution in the intestine and provided experimental evidence for the
      suggested absorption behaviour of low and highly permeable compounds.

PMID- 28743867
TI  - Using RNA sequencing to identify putative competing endogenous RNAs (ceRNAs)
      potentially regulating fat metabolism in bovine liver.
AB  - RNA sequencing has been extensively used to study specific gene expression
      patterns to discover potential key genes related to complex traits of interest in
      animals. Of note, a new regulatory mechanism builds a large-scale regulatory
      network among transcriptome, where lncRNAs act as competing endogenous RNAs
      (ceRNAs) to sponge miRNAs to regulate the expression of miRNA target genes post
      transcriptionally. In this study, we sequenced the cDNA and sRNA libraries of
      nine liver samples from three Holstein cows during dry period, early lactation,
      and peak of lactation with HiSeq platform. As a result, we identified 665 genes,
      57 miRNAs and 33 lncRNAs that displayed differential expression patterns across
      periods. Subsequently, a total of 41ceRNA pairs (lncRNA-mRNA) sharing 11 miRNAs
      were constructed including 30 differentially expressed genes. Importantly, 12
      among them were presented in our large metabolic networks, and predicted to
      influence the lipid metabolism through insulin, PI3K-Akt, MAPK, AMPK, mTOR, and
      PPAR signaling pathways, thus, these genes were considered as the most promising
      candidates for milk fat formation. To our knowledge, this is first investigation
      to profile the ceRNA regulatory networks of liver transcriptome that could affect
      milk fat synthesis in bovine, providing a new view of the regulatory mechanism of
      RNAs.

PMID- 28743869
TI  - Nicotinamide mononucleotide and related metabolites induce disease resistance
      against fungal phytopathogens in Arabidopsis and barley.
AB  - Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine
      dinucleotide (NAD), is known to act as a functional molecule in animals, whereas
      its function in plants is largely unknown. In this study, we found that NMN
      accumulated in barley cultivars resistant to phytopathogenic fungal Fusarium
      species. Although NMN does not possess antifungal activity, pretreatment with NMN
      and related metabolites enhanced disease resistance to Fusarium graminearum in
      Arabidopsis leaves and flowers and in barley spikes. The NMN-induced Fusarium
      resistance was accompanied by activation of the salicylic acid-mediated
      signalling pathway and repression of the jasmonic acid/ethylene-dependent
      signalling pathways in Arabidopsis. Since NMN-induced disease resistance was also
      observed in the SA-deficient sid2 mutant, an SA-independent signalling pathway
      also regulated the enhanced resistance induced by NMN. Compared with NMN, NAD and
      NADP, nicotinamide pretreatment had minor effects on resistance to F.
      graminearum. Constitutive expression of the NMNAT gene, which encodes a rate
      limiting enzyme for NAD biosynthesis, resulted in enhanced disease resistance in
      Arabidopsis. Thus, modifying the content of NAD-related metabolites can be used
      to optimize the defence signalling pathways activated in response to F.
      graminearum and facilitates the control of disease injury and mycotoxin
      accumulation in plants.

PMID- 28743868
TI  - Virus and dsRNA-triggered transcriptional responses reveal key components of
      honey bee antiviral defense.
AB  - Recent high annual losses of honey bee colonies are associated with many factors,
      including RNA virus infections. Honey bee antiviral responses include RNA
      interference and immune pathway activation, but their relative roles in antiviral
      defense are not well understood. To better characterize the mechanism(s) of honey
      bee antiviral defense, bees were infected with a model virus in the presence or
      absence of dsRNA, a virus associated molecular pattern. Regardless of sequence
      specificity, dsRNA reduced virus abundance. We utilized next generation
      sequencing to examine transcriptional responses triggered by virus and dsRNA at
      three time-points post-infection. Hundreds of genes exhibited differential
      expression in response to co-treatment of dsRNA and virus. Virus-infected bees
      had greater expression of genes involved in RNAi, Toll, Imd, and JAK-STAT
      pathways, but the majority of differentially expressed genes are not well
      characterized. To confirm the virus limiting role of two genes, including the
      well-characterized gene, dicer, and a probable uncharacterized cyclin dependent
      kinase in honey bees, we utilized RNAi to reduce their expression in vivo and
      determined that virus abundance increased, supporting their involvement in
      antiviral defense. Together, these results further our understanding of honey bee
      antiviral defense, particularly the role of a non-sequence specific dsRNA
      mediated antiviral pathway.

PMID- 28743870
TI  - Electronic components embedded in a single graphene nanoribbon.
AB  - The use of graphene in electronic devices requires a band gap, which can be
      achieved by creating nanostructures such as graphene nanoribbons. A wide variety
      of atomically precise graphene nanoribbons can be prepared through on-surface
      synthesis, bringing the concept of graphene nanoribbon electronics closer to
      reality. For future applications it is beneficial to integrate contacts and more
      functionality directly into single ribbons by using heterostructures. Here, we
      use the on-surface synthesis approach to fabricate a metal-semiconductor junction
      and a tunnel barrier in a single graphene nanoribbon consisting of 5- and 7-atom
      wide segments. We characterize the atomic scale geometry and electronic structure
      by combined atomic force microscopy, scanning tunneling microscopy, and
      conductance measurements complemented by density functional theory and transport
      calculations. These junctions are relevant for developing contacts in all
      graphene nanoribbon devices and creating diodes and transistors, and act as a
      first step toward complete electronic devices built into a single graphene
      nanoribbon.Adding functional electronic components to graphene nanoribbons
      requires precise control over their atomic structure. Here, the authors use a
      bottom-up approach to build a metal-semiconductor junction and a tunnel barrier
      directly into a single graphene nanoribbon, an exciting development for graphene
      based electronic devices.

PMID- 28743871
TI  - Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M.
      tuberculosis.
AB  - MarR family proteins are transcriptional regulators that control expression of
      bacterial proteins involved in metabolism, virulence, stress responses and multi
      drug resistance, mainly via ligand-mediated attenuation of DNA binding. Greater
      understanding of their underlying regulatory mechanism may open up new avenues
      for the effective treatment of bacterial infections. To gain molecular insight
      into the mechanism of Rv2887, a MarR family protein in M. tuberculosis, we first
      showed that it binds salicylate (SA) and para-aminosalicylic acid (PAS), its
      structural analogue and an antitubercular drug, in a 1:1 stoichiometry with high
      affinity. Subsequent determination and analysis of Rv2887 crystal structures in
      apo form, and in complex with SA, PAS and DNA showed that SA and PAS bind to
      Rv2887 at similar sites, and that Rv2887 interacts with DNA mainly by insertion
      of helix alpha4 into the major groove. Ligand binding triggers rotation of the
      wHTH domain of Rv2887 toward the dimerization domain, causing changes in protein
      conformation such that it can no longer bind to a 27 bp recognition sequence in
      the upstream region of gene Rv0560c. The structures provided here lay a
      foundation for the design of small molecules that target Rv2887, a potential new
      approach for the development of anti-mycobacterials.

PMID- 28743872
TI  - Social jetlag and metabolic control in non-communicable chronic diseases: a study
      addressing different obesity statuses.
AB  - Social jetlag - a measure of disruption of the circadian system - has been linked
      to obesity, but its association with metabolic complications in non-communicable
      chronic diseases (NCCDs) is unknown in the literature. We examined the
      associations between social jetlag and obesity status and metabolic parameters
      among individuals with NCCDs. Patients (n = 792) with NCCDs (obesity, systemic
      arterial hypertension, type 2 diabetes mellitus or dyslipidaemia) attended
      clinics of the public health service of the city of Uberlandia, Minas Gerais
      State, Brazil. They were classified in three obesity statuses: non-obese: BMI <
      30 kg/m2; metabolically healthy obese (MHO): BMI >= 30 kg/m2 and less than three
      high-risk biomarkers for metabolic syndrome; and metabolically unhealthy obese
      (MUO): BMI >= 30 kg/m2 and with high-risk values on three or more biomarkers for
      metabolic syndrome. After adjustments for confounding variables, social jetlag
      was positively associated with fasting glucose levels among all subjects (beta =
      0.08, p = 0.03) and MUO subjects (beta = 0.32, p < 0.001). Patients with social
      jetlag (>1 h) presented a significant odds ratio (OR) of being overweight (OR =
      2.0, confidence interval (CI) = 1.2-3.6, p = 0.006) and MUO (OR = 1.8, CI = 1.1
      2.8, p = 0.01). These results suggest that social jetlag is associated with a
      higher risk of overweight and related metabolic complications in individuals with
      NCCDs.

PMID- 28743873
TI  - Origin of clay minerals in Early Eocene volcanic paleosols on King George Island,
      Maritime Antarctica.
AB  - The paleoclimate during the Early Eocene in Maritime Antarctica is characterized
      by cool conditions without a pronounced dry season. Soils formed on volcanic
      material under such climate conditions in modern analogue environments are
      usually Andosols rich in nanocrystalline minerals without pedogenic smectite. The
      paleosols formed on volcanic material on King Georges Island are covered by
      basalts, dated by 6 new 40Ar/39Ar datings to 51-48 Ma, and are rich in smectite.
      A pedogenic origin of the smectites would suggest a semi-arid rather than a wet
      non-seasonal humid paleoclimate. To investigate the origin of the smectites in
      these paleosols we used X-ray diffraction and microscopic techniques. Minor
      mineralogical changes between the volcanic parent material and the paleosols and
      a homogenous distribution of smectites throughout the paleosol horizons indicate
      that these smectites were mainly inherited from the pyroclastic parent material,
      which was altered prior to surficial weathering. Nevertheless, the mineralogical
      properties, such as degree of crystallinity and octahedral site occupancy, of
      these smectites were modified during the ancient soil formation. Our findings
      highlight that trioctahedral smectites were a product of deuteric alteration of
      pyroclastic rocks and were progressively transformed to dioctahedral smectites
      during weathering in a soil environment on King George Island.

PMID- 28743874
TI  - Experimental demonstration of a reconfigurable electro-optic directed logic
      circuit using cascaded carrier-injection micro-ring resonators.
AB  - We experimentally demonstrate a reconfigurable electro-optic directed logic
      circuit which can perform any combinatorial logic operation using cascaded
      carrier-injection micro-ring resonators (MRRs), and the logic circuit is
      fabricated on the silicon-on-insulator (SOI) substrate with the standard
      commercial Complementary Metal-Oxide-Semiconductor (CMOS) fabrication process.
      PIN diodes embedded around MRRs are employed to achieve the carrier injection
      modulation. The operands are represented by electrical signals, which are applied
      to the corresponding MRRs to control their switching states. The operation result
      is directed to the output port in the form of light. For proof of principle,
      several logic operations of three-operand with the operation speed of 100 Mbps
      are demonstrated successfully.

PMID- 28743875
TI  - Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to
      Facilitate Viral Propagation.
AB  - The life cycle of hepatitis C virus (HCV) is highly dependent on host proteins
      for virus propagation. By transcriptome sequencing analysis, we identified host
      genes that were highly differentially expressed in HCV-infected cells. Of these
      candidates, we selected Death receptor 6 (DR6) for further characterization. DR6
      is an orphan member of the tumor necrosis factor receptor superfamily. In the
      present study, we demonstrated that both mRNA and protein levels of DR6 were
      increased in the context of HCV replication. We further showed that promoter
      activity of DR6 was increased by HCV infection. By employing promoter-linked
      reporter assay, we showed that HCV upregulated DR6 via ROS-mediated NF-kappaB
      pathway. Both mRNA and protein levels of DR6 were increased by NS4B or NS5A.
      However, NS5A but not NS4B specifically interacted with DR6. We showed that HCV
      modulated JNK, p38 MAPK, STAT3, and Akt signaling pathways in a DR6-dependent
      manner. Interestingly, Akt signaling cascade was regulated by protein interplay
      between DR6 and NS5A. Silencing of DR6 expression resulted in decrease of
      infectious HCV production without affecting viral entry, replication, and
      translation. Together, these data indicate that HCV modulates DR6 signaling
      pathway for viral propagation and may contribute to HCV-mediated pathogenesis.

PMID- 28743876
TI  - Environmentally stable interface of layered oxide cathodes for sodium-ion
      batteries.
AB  - Sodium-ion batteries are strategically pivotal to achieving large-scale energy
      storage. Layered oxides, especially manganese-based oxides, are the most popular
      cathodes due to their high reversible capacity and use of earth-abundant
      elements. However, less noticed is the fact that the interface of layered
      cathodes always suffers from atmospheric and electrochemical corrosion, leading
      to severely diminished electrochemical properties. Herein, we demonstrate an
      environmentally stable interface via the superficial concentration of titanium,
      which not only overcomes the above limitations, but also presents unique surface
      chemical/electrochemical properties. The results show that the atomic-scale
      interface is composed of spinel-like titanium (III) oxides, enhancing the
      structural/electrochemical stability and electronic/ionic conductivity.
      Consequently, the interface-engineered electrode shows excellent cycling
      performance among all layered manganese-based cathodes, as well as high-energy
      density. Our findings highlight the significance of a stable interface and,
      moreover, open opportunities for the design of well-tailored cathode materials
      for sodium storage.The interface of layered cathodes for sodium ion batteries is
      subject to atmospheric and electrochemical corrosions. Here, the authors
      demonstrate an environmentally stable interface via titanium enriched surface
      reconstruction in a layered manganese-based oxide.

PMID- 28743877
TI  - Chronic activation of JNK JAK/STAT and oxidative stress signalling causes the
      loser cell status.
AB  - Cell competition is a form of cell interaction that causes the elimination of
      less fit cells, or losers, by wild-type (WT) cells, influencing overall tissue
      health. Several mutations can cause cells to become losers; however, it is not
      known how. Here we show that Drosophila wing disc cells carrying functionally
      unrelated loser mutations (Minute and mahjong) display the common activation of
      multiple stress signalling pathways before cell competition and find that these
      pathways collectively account for the loser status. We find that JNK signalling
      inhibits the growth of losers, while JAK/STAT signalling promotes competition
      induced winner cell proliferation. Furthermore, we show that losers display
      oxidative stress response activation and, strikingly, that activation of this
      pathway alone, by Nrf2 overexpression, is sufficient to prime cells for their
      elimination by WT neighbours. Since oxidative stress and Nrf2 are linked to
      several diseases, cell competition may occur in a number of pathological
      conditions.Cell competition causes the removal of less fit cells ('losers') but
      why some gene mutations turn cells into losers is unclear. Here, the authors show
      that Drosophila wing disc cells carrying some loser mutations activate Nrf2 and
      JNK signalling, which contribute to the loser status.

PMID- 28743878
TI  - An all-in-one UniSam vector system for efficient gene activation.
AB  - We have generated a drug-free, all-in-one dCAS9-SAM vector that can activate
      endogenous gene expression with the potential to modify cell fate. We demonstrate
      that this strategy can be used in a number of cell lines and avoids exceptionally
      high levels of gene expression that are observed in standard transgenic
      approaches. Compared to the multi-plasmid system, this all-in-one vector
      activates gene expression to a comparable level but the reduced overall DNA
      content results in significantly higher viability of transfected cells. This
      allowed us to use the RUNX1C-GFP human embryonic stem cell reporter cell line to
      monitor gene activation in individual cells and to show that activation could
      occur at all stages of the cell cycle.

PMID- 28743879
TI  - Network-Centric Interventions to Contain the Syphilis Epidemic in San Francisco.
AB  - The number of reported early syphilis cases in San Francisco has increased
      steadily since 2005. It is not yet clear what factors are responsible for such an
      increase. A recent analysis of the sexual contact network of men who have sex
      with men with syphilis in San Francisco has discovered a large connected
      component, members of which have a significantly higher chance of syphilis and
      HIV compared to non-member individuals. This study investigates whether it is
      possible to exploit the existence of the largest connected component to design
      new notification strategies that can potentially contribute to reducing the
      number of cases. We develop a model capable of incorporating multiple types of
      notification strategies and compare the corresponding incidence of syphilis.
      Through extensive simulations, we show that notifying the community of the
      infection state of few central nodes appears to be the most effective approach,
      balancing the cost of notification and the reduction of syphilis incidence.
      Additionally, among the different measures of centrality, the eigenvector
      centrality reveals to be the best to reduce the incidence in the long term as
      long as the number of missing links (non-disclosed contacts) is not very large.

PMID- 28743880
TI  - (t, n) Threshold d-Level Quantum Secret Sharing.
AB  - Most of Quantum Secret Sharing(QSS) are (n, n) threshold 2-level schemes, in
      which the 2-level secret cannot be reconstructed until all n shares are
      collected. In this paper, we propose a (t, n) threshold d-level QSS scheme, in
      which the d-level secret can be reconstructed only if at least t shares are
      collected. Compared with (n, n) threshold 2-level QSS, the proposed QSS provides
      better universality, flexibility, and practicability. Moreover, in this scheme,
      any one of the participants does not know the other participants' shares, even
      the trusted reconstructor Bob 1 is no exception. The transformation of the
      particles includes some simple operations such as d-level CNOT, Quantum Fourier
      Transform(QFT), Inverse Quantum Fourier Transform(IQFT), and generalized Pauli
      operator. The transformed particles need not to be transmitted from one
      participant to another in the quantum channel. Security analysis shows that the
      proposed scheme can resist intercept-resend attack, entangle-measure attack,
      collusion attack, and forgery attack. Performance comparison shows that it has
      lower computation and communication costs than other similar schemes when 2 < t <
      n - 1.

PMID- 28743881
TI  - Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord
      regeneration in zebrafish.
AB  - The inhibitory extracellular matrix in a spinal lesion site is a major impediment
      to axonal regeneration in mammals. In contrast, the extracellular matrix in
      zebrafish allows substantial axon re-growth, leading to recovery of movement.
      However, little is known about regulation and composition of the growth-promoting
      extracellular matrix. Here we demonstrate that activity of the Wnt/beta-catenin
      pathway in fibroblast-like cells in the lesion site is pivotal for axon re-growth
      and functional recovery. Wnt/beta-catenin signaling induces expression of
      col12a1a/b and deposition of Collagen XII, which is necessary for axons to
      actively navigate the non-neural lesion site environment. Overexpression of
      col12a1a rescues the effects of Wnt/beta-catenin pathway inhibition and is
      sufficient to accelerate regeneration. We demonstrate that in a vertebrate of
      high regenerative capacity, Wnt/beta-catenin signaling controls the composition
      of the lesion site extracellular matrix and we identify Collagen XII as a
      promoter of axonal regeneration. These findings imply that the Wnt/beta-catenin
      pathway and Collagen XII may be targets for extracellular matrix manipulations in
      non-regenerating species.Following spinal injury in zebrafish, non-neural cells
      establish an extracellular matrix to promote axon re-growth but how this is
      regulated is unclear. Here, the authors show that Wnt/beta-catenin signaling in
      fibroblast-like cells at a lesion activates axon re-growth via deposition of
      Collagen XII.

PMID- 28743882
TI  - Hyperoside pre-treatment prevents glomerular basement membrane damage in diabetic
      nephropathy by inhibiting podocyte heparanase expression.
AB  - Glomerular basement membrane (GBM) damage plays a pivotal role in pathogenesis of
      albuminuria in diabetic nephropathy (DN). Heparan sulfate (HS) degradation
      induced by podocyte heparanase is the major cause of GBM thickening and abnormal
      perm-selectivity. In the present study, we aimed to examine the prophylactic
      effect of hyperoside on proteinuria development and GBM damage in DN mouse model
      and the cultured mouse podocytes. Pre-treatment with hyperoside (30 mg/kg/d) for
      four weeks could significantly decrease albuminuria, prevent GBM damage and
      oxidative stress in diabetes mellitus (DM) mice. Immunofluorescence staining,
      Real time PCR and Western blot analysis showed that decreased HS contents and
      increased heparanase expression in DN mice were also significantly improved by
      hyperoside pre-treatment. Meanwhile, transmission electron microscope imaging
      showed that hyperoside significantly alleviated GBM thickening in DN mice. In
      addition, hyperoside pre-treatment inhibited the increased heparanase gene (HPR1)
      promoter activity and heparanase expression induced by high glucose or reactive
      oxidative species (ROS) in cultured podocytes. Our data suggested that hyperoside
      has a prophylactic effect on proteinuria development and GBM damage in DM mice by
      decreasing podocyte heparanase expression.

PMID- 28743883
TI  - Metabolic pathway and cell adaptation mechanisms revealed through genomic,
      proteomic and transcription analysis of a Sphingomonas haloaromaticamans strain
      degrading ortho-phenylphenol.
AB  - Ortho-phenylphenol (OPP) is a fungicide contained in agro-industrial effluents
      produced by fruit-packaging plants. Within the frame of developing bio-strategies
      to detoxify these effluents, an OPP-degrading Sphingomonas haloaromaticamans
      strain was isolated. Proteins/genes with a putative catabolic role and bacterium
      adaptation mechanisms during OPP degradation were identified via genomic and
      proteomic analysis. Transcription analysis of all putative catabolic genes
      established their role in the metabolism of OPP. The formation of key
      transformation products was verified by chromatographic analysis. Genomic
      analysis identified two orthologous operons encoding the ortho-cleavage of
      benzoic acid (BA) (ben/cat). The second ben/cat operon was located in a 92-kb
      scaffold along with (i) an operon (opp) comprising genes for the transformation
      of OPP to BA and 2-hydroxypenta-2,4-dienoate (and genes for its transformation)
      and (ii) an incomplete biphenyl catabolic operon (bph). Proteomics identified 13
      up-regulated catabolic proteins when S. haloaromaticamans was growing on OPP
      and/or BA. Transcription analysis verified the key role of the catabolic operons
      located in the 92-kb scaffold, and flanked by transposases, on the transformation
      of OPP by S. haloaromaticamans. A flavin-dependent monoxygenase (OppA1), one of
      the most up-regulated proteins in the OPP-growing cells, was isolated via
      heterologous expression and its catabolic activity was verified in vitro.

PMID- 28743884
TI  - Molecular mechanisms of Bdp1 in TFIIIB assembly and RNA polymerase III
      transcription initiation.
AB  - Initiation of gene transcription by RNA polymerase (Pol) III requires the
      activity of TFIIIB, a complex formed by Brf1 (or Brf2), TBP (TATA-binding
      protein), and Bdp1. TFIIIB is required for recruitment of Pol III and to promote
      the transition from a closed to an open Pol III pre-initiation complex, a process
      dependent on the activity of the Bdp1 subunit. Here, we present a crystal
      structure of a Brf2-TBP-Bdp1 complex bound to DNA at 2.7 A resolution, integrated
      with single-molecule FRET analysis and in vitro biochemical assays. Our study
      provides a structural insight on how Bdp1 is assembled into TFIIIB complexes,
      reveals structural and functional similarities between Bdp1 and Pol II factors
      TFIIA and TFIIF, and unravels essential interactions with DNA and with the
      upstream factor SNAPc. Furthermore, our data support the idea of a concerted
      mechanism involving TFIIIB and RNA polymerase III subunits for the closed to open
      pre-initiation complex transition.Transcription initiation by RNA polymerase III
      requires TFIIIB, a complex formed by Brf1/Brf2, TBP and Bdp1. Here, the authors
      describe the crystal structure of a Brf2-TBP-Bdp1 complex bound to a DNA promoter
      and characterize the role of Bdp1 in TFIIIB assembly and pre-initiation complex
      formation.

PMID- 28743885
TI  - Genome-wide identification of thyroid hormone receptor targets in the remodeling
      intestine during Xenopus tropicalis metamorphosis.
AB  - Thyroid hormone (T3) affects development and metabolism in vertebrates. We have
      been studying intestinal remodeling during T3-dependent Xenopus metamorphosis as
      a model for organ maturation and formation of adult organ-specific stem cells
      during vertebrate postembryonic development, a period characterized by high
      levels of plasma T3. T3 is believed to affect development by regulating target
      gene transcription through T3 receptors (TRs). While many T3 response genes have
      been identified in different animal species, few have been shown to be direct
      target genes in vivo, especially during development. Here we generated a set of
      genomic microarray chips covering about 8000 bp flanking the predicted
      transcription start sites in Xenopus tropicalis for genome wide identification of
      TR binding sites. By using the intestine of premetamorphic tadpoles treated with
      or without T3 and for chromatin immunoprecipitation assays with these chips, we
      determined the genome-wide binding of TR in the control and T3-treated tadpole
      intestine. We further validated TR binding in vivo and analyzed the regulation of
      selected genes. We thus identified 278 candidate direct TR target genes. We
      further provided evidence that these genes are regulated by T3 and likely
      involved in the T3-induced formation of adult intestinal stem cells during
      metamorphosis.

PMID- 28743886
TI  - The minimum resting-state fNIRS imaging duration for accurate and stable mapping
      of brain connectivity network in children.
AB  - Resting-state functional near-infrared spectroscopy (fNIRS) is a potential
      technique for the study of brain functional connectivity (FC) and networks in
      children. However, the necessary fNIRS scanning duration required to map accurate
      and stable functional brain connectivity and graph theory metrics in the resting
      state brain activity remains largely unknown. Here, we acquired resting-state
      fNIRS imaging data from 53 healthy children to provide the first empirical
      evidence for the minimum imaging time required to obtain accurate and stable FC
      and graph theory metrics of brain network activity (e.g., nodal efficiency and
      network global and local efficiency). Our results showed that FC was accurately
      and stably achieved after 7.0-min fNIRS imaging duration, whereas the necessary
      scanning time for accurate and stable network measures was a minimum of 2.5 min
      at low network thresholds. These quantitative results provide direct evidence for
      the choice of the resting-state fNIRS imaging time in children in brain FC and
      network topology study. The current study also demonstrates that these methods
      are feasible and cost-effective in the application of time-constrained infants
      and critically ill children.

PMID- 28743887
TI  - Tumor-Derived Exosomes Induce the Formation of Neutrophil Extracellular Traps:
      Implications For The Establishment of Cancer-Associated Thrombosis.
AB  - Cancer patients are at an increased risk of developing thromboembolic
      complications. Several mechanisms have been proposed to explain cancer-associated
      thrombosis including the release of tumor-derived extracellular vesicles and the
      activation of host vascular cells. It was proposed that neutrophil extracellular
      traps (NETs) contribute to the prothrombotic phenotype in cancer. In this study,
      we evaluated the possible cooperation between tumor-derived exosomes and NETs in
      cancer-associated thrombosis. Female BALB/c mice were orthotopically injected
      with 4T1 breast cancer cells. The tumor-bearing animals exhibited increased
      levels of plasma DNA and myeloperoxidase in addition to significantly increased
      numbers of circulating neutrophils. Mice were subjected to either Rose
      Bengal/laser-induced venous thrombosis or ferric chloride-induced arterial
      thrombosis models. The tumor-bearing mice exhibited accelerated thrombus
      formation in both models compared to tumor-free animals. Treatment with
      recombinant human DNase 1 reversed the prothrombotic phenotype of tumor-bearing
      mice in both models. Remarkably, 4T1-derived exosomes induced NET formation in
      neutrophils from mice treated with granulocyte colony-stimulating factor (G-CSF).
      In addition, tumor-derived exosomes interacted with NETs under static conditions.
      Accordingly, the intravenous administration of 4T1-derived exosomes into G-CSF
      treated mice significantly accelerated venous thrombosis in vivo. Taken together,
      our observations suggest that tumor-derived exosomes and neutrophils may act
      cooperatively in the establishment of cancer-associated thrombosis.

PMID- 28743888
TI  - Multiplication rate variation in the human malaria parasite Plasmodium
      falciparum.
AB  - It is important to understand intrinsic variation in asexual blood stage
      multiplication rates of the most virulent human malaria parasite, Plasmodium
      falciparum. Here, multiplication rates of long-term laboratory adapted parasite
      clones and new clinical isolates were measured, using a newly standardised assay
      of growth from low starting density in replicate parallel cultures with
      erythrocytes from multiple different donors, across multiple cycles.
      Multiplication rates of long-term established clones were between 7.6 and 10.5
      fold per 48 hours, with clone Dd2 having a higher rate than others (clones 3D7,
      HB3 and D10). Parasite clone-specific growth was then analysed in co-culture
      assays with all possible heterologous pairwise combinations. This showed that co
      culture of different parasites did not affect their replication rates, indicating
      that there were no suppressive interactions operating between parasites.
      Multiplication rates of eleven new clinical isolates were measured after a few
      weeks of culture, and showed a spectrum of replication rates between 2.3 and 6.0
      fold per 48 hours, the entire range being lower than for the long-term laboratory
      adapted clones. Multiplication rate estimates remained stable over time for
      several isolates tested repeatedly up to three months after culture initiation,
      indicating considerable persistence of this important trait variation.

PMID- 28743889
TI  - Limbal stromal cells derived from porcine tissue demonstrate mesenchymal
      characteristics in vitro.
AB  - Limbal stromal cells (LSCs) from the human ocular surface display mesenchymal
      stromal cell characteristics in vitro. In this study, we isolated cells from the
      porcine limbal stroma (pLSCs), characterised them, and evaluated their ability to
      support angiogenesis and the culture of porcine limbal epithelial stem cells
      (pLESCs). The isolated cells adhered to plastic and grew in monolayers in vitro
      using serum-supplemented or serum-free medium. The pLSCs demonstrated expression
      of CD29, and cross-reactivity with anti-human CD45, CD90, CD105, CD146, and HLA
      ABC. However, expression of CD105, CD146 and HLA-ABC reduced when cultured in
      serum-free medium. PLSCs did not undergo adipogenic or osteogenic
      differentiation, but differentiated towards the chondrogenic lineage. Isolated
      cells were also co-cultured with human umbilical vein endothelial cells (HUVECs)
      in star-shaped Poly(ethylene glycol) (starPEG)-heparin hydrogels to assess their
      pericyte capacity which supported angiogenesis networks of HUVECs. PLSCs
      supported the three dimensional HUVEC network for 7 days. The isolated cells were
      further growth-arrested and evaluated as feeder cells for pLESC expansion on silk
      fibroin membranes, as a potential carrier material for transplantation. PLSCs
      supported the growth of pLESCs comparably to murine 3T3 cells. In conclusion,
      although pLSCs were not completely comparable to their human counterpart, they
      display several mesenchymal-like characteristics in vitro.

PMID- 28743890
TI  - Polymorphism in ERCC1 confers susceptibility of coronary artery disease and
      severity of coronary artery atherosclerosis in a Chinese Han population.
AB  - Excision repair cross-complementing 1 (ERCC1) gene encodes ERCC1 protein, which
      is mainly responsible for the repair of DNA damage in different diseases
      including coronary artery atherosclerosis by acting as a rate-limiting element in
      nucleotide excision repair (NER). Using a three-stage case-control study with
      3037 coronary artery disease (CAD) patients and 3002 controls, we investigated
      associations of three single nucleotide polymorphisms (SNPs) with CAD risk and
      severity of coronary artery atherosclerosis in Chinese Han population. In the
      discovery set, the variant allele T of rs11615 was significantly associated with
      higher CAD risk (adjusted OR = 1.27, P = 0.006) and severity of coronary artery
      atherosclerosis (adjusted OR = 1.54, P = 0.003). These associations were more
      remarkable in the merged set (adjusted OR = 1.23, P = 8 * 10-6 for CAD risk;
      adjusted OR = 1.36, P = 4.3 * 10-5 for severity of coronary artery
      atherosclerosis). And the expression level of ERCC1 was significantly higher in
      CAD cases than controls. Multiplicative interactions among SNP rs11615, alcohol
      drinking, history of T2DM, and history of hyperlipidemia could increase 5.06-fold
      risk of CAD (P = 1.59 * 10-9). No significant association of rs2298881 and
      rs3212986 with CAD risk was identified. Taken together, SNP rs11615 in ERCC1 gene
      might confer susceptibility to CAD and severity of coronary atherosclerosis in a
      Chinese Han population.

PMID- 28743891
TI  - Advantages of phylogenetic distance based constrained ordination analyses for the
      examination of microbial communities.
AB  - Recently developed high throughput molecular techniques such as massively
      parallel sequencing and phylogenetic microarrays generate vast datasets providing
      insights into microbial community structure and function. Because of the high
      dimensionality of these datasets, multivariate ordination analyses are often
      employed to examine such data. Here, we show how the use of phylogenetic distance
      based redundancy analysis provides ecological interpretation of microbial
      community differences. We also extend the previously developed method of
      principal response curves to incorporate phylogenetic distance measure, and we
      demonstrate the improved ability of this approach to provide ecologically
      relevant insights into temporal alterations of microbial communities.

PMID- 28743892
TI  - DYRK1B mutations associated with metabolic syndrome impair the chaperone
      dependent maturation of the kinase domain.
AB  - Two missense mutations of the DYRK1B gene have recently been found to co
      segregate with a rare autosomal-dominant form of metabolic syndrome. This gene
      encodes a member of the DYRK family of protein kinases, which depend on tyrosine
      autophosphorylation to acquire the catalytically active conformation. The
      mutations (H90P and R102C) affect a structural element named DYRK homology (DH)
      box and did not directly interfere with the conformation of the catalytic domain
      in a structural model of DYRK1B. Cellular assays showed that the mutations did
      not alter the specific activity of mature kinase molecules. However, a
      significant part of the mutant DYRK1B protein accumulated in detergent-insoluble
      cytoplasmic aggregates and was underphosphorylated on tyrosine. The mutant DYRK1B
      variants were more vulnerable to the HSP90 inhibitor ganetespib and showed
      enhanced binding to the co-chaperone CDC37 as compared to wild type DYRK1B. These
      results support the hypothesis that the mutations in the DH box interfere with
      the maturation of DYRK1B by tyrosine autophosphorylation and compromise the
      conformational stability of the catalytic domain, which renders the kinase
      susceptible to misfolding.

PMID- 28743893
TI  - Complex magnetic incommensurability and electronic charge transfer through the
      ferroelectric transition in multiferroic Co3TeO6.
AB  - Polarized and unpolarized neutron diffractions have been carried out to
      investigate the nature of the magnetic structures and transitions in monoclinic
      Co3TeO6. As the temperature is lowered below 26 K long range order develops,
      which is fully incommensurate (ICM) in all three crystallographic directions.
      Below 19.5 K additional commensurate magnetic peaks develop, consistent with the
      Gamma4 irreducible representation, along with a splitting of the ICM peaks along
      the h direction which indicates that there are two separate sets of magnetic
      modulation vectors. Below 18 K, this small additional magnetic incommensurability
      disappears, ferroelectricity develops, an additional commensurate magnetic
      structure consistent with Gamma3 irreducible representation appears, and the k
      component of the ICM wave vector disappears. Synchrotron x-ray diffraction
      measurements demonstrate that there is a significant shift of the electronic
      charge distribution from the Te ions at the crystallographic 8 f sites to the
      neighboring Co and O ions. These results, together with the unusually small
      electric polarization, its strong magnetic field dependence, and the negative
      thermal expansion in all three lattice parameters, suggest this material is an
      antiferroelectric. Below15 K the k component of the ICM structure reappears,
      along with second-order ICM Bragg peaks, which polarized neutron data demonstrate
      are magnetic in origin.

PMID- 28743894
TI  - CREB Regulates Distinct Adaptive Transcriptional Programs in Astrocytes and
      Neurons.
AB  - The cyclic AMP response element binding protein (CREB) is a primary hub of
      activity-driven genetic programs in neurons controlling plasticity, neurogenesis
      and survival. By contrast, the gene networks coordinated by CREB in astrocytes
      are unknown despite the fact that the astrocytic CREB is also activity-driven and
      neuroprotective. Herein we identified the transcriptional programs regulated by
      CREB in astrocytes as compared to neurons using, as study materials,
      transcriptome databases of astrocyte exposed to well-known activators of CREB
      dependent transcription as well as publicly available transcriptomes of neuronal
      cultures. Functional CREB signatures were extracted from the transcriptomes using
      Gene Ontology, adult-brain gene lists generated by Translating Ribosome Affinity
      Purification (TRAP) and CREB-target gene repositories. We found minimal overlap
      between CREB signatures in astrocytes and neurons. In astrocytes, the top triad
      of functions regulated by CREB consists of 'Gene expression', 'Mitochondria', and
      'Signalling', while in neurons it is 'Neurotransmission', 'Signalling' and 'Gene
      expression', the latter two being represented by different genes from those in
      astrocytes. The newly generated databases will provide a tool to explore novel
      means whereby CREB impinges on brain functions requiring adaptive, long-lasting
      changes by coordinating transcriptional cascades in astrocytes.

PMID- 28743895
TI  - Eternal non-Markovianity: from random unitary to Markov chain realisations.
AB  - The theoretical description of quantum dynamics in an intriguing way does not
      necessarily imply the underlying dynamics is indeed intriguing. Here we show how
      a known very interesting master equation with an always negative decay rate
      [eternal non-Markovianity (ENM)] arises from simple stochastic Schrodinger
      dynamics (random unitary dynamics). Equivalently, it may be seen as arising from
      a mixture of Markov (semi-group) open system dynamics. Both these approaches lead
      to a more general family of CPT maps, characterized by a point within a parameter
      triangle. Our results show how ENM quantum dynamics can be realised easily in the
      laboratory. Moreover, we find a quantum time-continuously measured (quantum
      trajectory) realisation of the dynamics of the ENM master equation based on
      unitary transformations and projective measurements in an extended Hilbert space,
      guided by a classical Markov process. Furthermore, a Gorini-Kossakowski-Sudarshan
      Lindblad (GKSL) representation of the dynamics in an extended Hilbert space can
      be found, with a remarkable property: there is no dynamics in the ancilla state.
      Finally, analogous constructions for two qubits extend these results from non-CP
      divisible to non-P-divisible dynamics.

PMID- 28743896
TI  - Rapid screening for specific glycosylation and pathogen interactions on a 78
      species avian egg white glycoprotein microarray.
AB  - There is an urgent need for discovery of novel antimicrobials and carbohydrate
      based anti-adhesive strategies are desirable as they may not promote resistance.
      Discovery of novel anti-adhesive molecules from natural product libraries will
      require the use of a high throughput screening platform. Avian egg white (EW)
      provides nutrition for the embryo and protects against infection, with
      glycosylation responsible for binding certain pathogens. In this study, a
      microarray platform of 78 species of avian EWs was developed and profiled for
      glycosylation using a lectin panel with a wide range of carbohydrate
      specificities. The dominating linkages of sialic acid in EWs were determined for
      the first time using the lectins MAA and SNA-I. EW glycosylation similarity among
      the different orders of birds did not strictly depend on phylogenetic
      relationship. The interactions of five strains of bacterial pathogens, including
      Escherichia coli, Staphylococcus aureus and Vibrio cholera, identified a number
      of EWs as potential anti-adhesives, with some as strain- or species-specific. Of
      the two bacterial toxins examined, shiga-like toxin 1 subunit B bound to ten EWs
      with similar glycosylation more intensely than pigeon EW. This study provides a
      unique platform for high throughput screening of natural products for specific
      glycosylation and pathogen interactions. This platform may provide a useful
      platform in the future for discovery of anti-adhesives targeted for strain and
      species specificity.

PMID- 28743897
TI  - The healing of alveolar bone defects with novel bio-implants composed of Ad-BMP9
      transfected rDFCs and CHA scaffolds.
AB  - Cells, scaffolds, and growth factors play important roles in bone regeneration.
      Bone morphogenetic protein 9 (BMP9), a member of BMP family, could facilitate
      osteogenesis by regulating growth factors and promoting angiogenesis. Similar to
      other stem cells, rat dental follicle stem cells (rDFCs), the precursor cells of
      cementoblasts, osteoblasts and periodontal ligament cells, can self-renew and
      exhibit multipotential capacity. Coralline hydroxyapatite (CHA) has good
      biocompatibility and conductivity required for bone tissue engineering. Here, we
      reported that BMP9 could enhance the osteogenic differentiation of rDFCs in cell
      culture. Moreover, our results suggested that BMP9 acted through the Smad1/5/8
      signaling pathway. We also produced a novel scaffold that encompasses bio
      degradable CHA seeded with recombinant adenoviruses expressing BMP9-transfected
      rDFCs (Ad-BMP9-transfected rDFCs). With this implant, we achieved more alveolar
      bone regeneration in the alveolar bone defect compared to blank group, CHA group
      and rDFCs group. Our results provided a novel bio-implants composed of Ad-BMP9
      transfected rDFCs and CHA scaffolds and its mechanism is regarding the activation
      of Smad1/5/8 signaling pathway in BMP9-induced rDFCs osteogenesis.

PMID- 28743898
TI  - Achievement of Sustained Net Plasma Heating in a Fusion Experiment with the
      Optometrist Algorithm.
AB  - Many fields of basic and applied science require efficiently exploring complex
      systems with high dimensionality. An example of such a challenge is optimising
      the performance of plasma fusion experiments. The highly-nonlinear and temporally
      varying interaction between the plasma, its environment and external controls
      presents a considerable complexity in these experiments. A further difficulty
      arises from the fact that there is no single objective metric that fully captures
      both plasma quality and equipment constraints. To efficiently optimise the
      system, we develop the Optometrist Algorithm, a stochastic perturbation method
      combined with human choice. Analogous to getting an eyeglass prescription, the
      Optometrist Algorithm confronts a human operator with two alternative
      experimental settings and associated outcomes. A human operator then chooses
      which experiment produces subjectively better results. This innovative technique
      led to the discovery of an unexpected record confinement regime with positive net
      heating power in a field-reversed configuration plasma, characterised by a >50%
      reduction in the energy loss rate and concomitant increase in ion temperature and
      total plasma energy.

PMID- 28743899
TI  - Thrombopoiesis is spatially regulated by the bone marrow vasculature.
AB  - In mammals, megakaryocytes (MKs) in the bone marrow (BM) produce blood platelets,
      required for hemostasis and thrombosis. MKs originate from hematopoietic stem
      cells and are thought to migrate from an endosteal niche towards the vascular
      sinusoids during their maturation. Through imaging of MKs in the intact BM, here
      we show that MKs can be found within the entire BM, without a bias towards bone
      distant regions. By combining in vivo two-photon microscopy and in situ light
      sheet fluorescence microscopy with computational simulations, we reveal
      surprisingly slow MK migration, limited intervascular space, and a vessel-biased
      MK pool. These data challenge the current thrombopoiesis model of MK migration
      and support a modified model, where MKs at sinusoids are replenished by
      sinusoidal precursors rather than cells from a distant periostic niche. As MKs do
      not need to migrate to reach the vessel, therapies to increase MK numbers might
      be sufficient to raise platelet counts.Megakaryocyte maturation is thought to
      occur as the cells migrate from a vessel-distant (endosteal) niche to the vessel
      within the bone. Here, the authors show that megakaryocytes represent largely
      sessile cells in close contact with the vasculature and homogeneously distributed
      in the bone marrow.

PMID- 28743900
TI  - Long-term hepatitis B infection in a scalable hepatic co-culture system.
AB  - Hepatitis B virus causes chronic infections in 250 million people worldwide.
      Chronic hepatitis B virus carriers are at risk of developing fibrosis, cirrhosis,
      and hepatocellular carcinoma. A prophylactic vaccine exists and currently
      available antivirals can suppress but rarely cure chronic infections. The study
      of hepatitis B virus and development of curative antivirals are hampered by a
      scarcity of models that mimic infection in a physiologically relevant, cellular
      context. Here, we show that cell-culture and patient-derived hepatitis B virus
      can establish persistent infection for over 30 days in a self-assembling, primary
      hepatocyte co-culture system. Importantly, infection can be established without
      antiviral immune suppression, and susceptibility is not donor dependent. The
      platform is scalable to microwell formats, and we provide proof-of-concept for
      its use in testing entry inhibitors and antiviral compounds.The lack of models
      that mimic hepatitis B virus (HBV) infection in a physiologically relevant
      context has hampered drug development. Here, Winer et al. establish a self
      assembling, primary hepatocyte co-culture system that can be infected with
      patient-derived HBV without further modifications.

PMID- 28743901
TI  - Temperature and energy effects on secondary electron emission from SiC ceramics
      induced by Xe17+ ions.
AB  - Secondary electron emission yield from the surface of SiC ceramics induced by
      Xe17+ ions has been measured as a function of target temperature and incident
      energy. In the temperature range of 463-659 K, the total yield gradually
      decreases with increasing target temperature. The decrease is about 57% for 3.2
      MeV Xe17+ impact, and about 62% for 4.0 MeV Xe17+ impact, which is much larger
      than the decrease observed previously for ion impact at low charged states. The
      yield dependence on the temperature is discussed in terms of work function,
      because both kinetic electron emission and potential electron emission are
      influenced by work function. In addition, our experimental data show that the
      total electron yield gradually increases with the kinetic energy of projectile,
      when the target is at a constant temperature higher than room temperature. This
      result can be explained by electronic stopping power which plays an important
      role in kinetic electron emission.

PMID- 28743902
TI  - Structure of spin excitations in heavily electron-doped Li0.8Fe0.2ODFeSe
      superconductors.
AB  - Heavily electron-doped iron-selenide high-transition-temperature (high-T c)
      superconductors, which have no hole Fermi pockets, but have a notably high T c,
      have challenged the prevailing s +/- pairing scenario originally proposed for
      iron pnictides containing both electron and hole pockets. The microscopic
      mechanism underlying the enhanced superconductivity in heavily electron-doped
      iron-selenide remains unclear. Here, we used neutron scattering to study the spin
      excitations of the heavily electron-doped iron-selenide material Li0.8Fe0.2ODFeSe
      (T c = 41 K). Our data revealed nearly ring-shaped magnetic resonant excitations
      surrounding (pi, pi) at ~21 meV. As the energy increased, the spin excitations
      assumed a diamond shape, and they dispersed outward until the energy reached ~60
      meV and then inward at higher energies. The observed energy-dependent momentum
      structure and twisted dispersion of spin excitations near (pi, pi) are analogous
      to those of hole-doped cuprates in several aspects, thus implying that such spin
      excitations are essential for the remarkably high T c in these materials.The
      microscopic mechanism underlying an enhanced superconductivity in electron-doped
      iron selenide superconductor remains unclear. Here, Pan et al. report the spin
      excitations of Li0.8Fe0.2ODFeSe, revealing analogous momentum structure and
      dispersion to hole-doped cuprates.

PMID- 28743903
TI  - A 3  degrees C global RCP8.5 emission trajectory cancels benefits of European
      emission reductions on air quality.
AB  - Despite the international agreement to reduce global warming to below 2  degrees
      C, the Intended Nationally Determined Contributions submitted for the COP21 would
      lead to a global temperature rise of about 3  degrees C. The relative
      consequences of such a one-degree additional warming have not yet been
      investigated for regional air quality. Here we found that a + 3  degrees C global
      pollutant emission trajectory with respect to pre-industrial climate (reached
      along the 2040-2069 period under a RCP8.5 scenario) would significantly increase
      European ozone levels relative to a 2  degrees C one (reached along the 2028-2057
      period under a RCP4.5 scenario). This increase is particularly high over
      industrial regions, large urban areas, and over Southern Europe and would
      annihilate the benefits of emission reduction policies. The regional ozone
      increase mainly stems from the advection of ozone at Europe's boundaries,
      themselves due to high global methane concentrations associated with the RCP8.5
      emission scenario. These results make regional emission regulation, combined with
      emissions-reduction policies for global methane, of crucial importance.Current
      national pledges to reduce greenhouse gas emissions track to a temperature rise
      of about 3  degrees C. Here the authors use future projections to show that 3 
      degrees C warming under a business as usual scenario would result in large
      increases in ozone concentrations, off-setting any benefits from mitigation
      policies.

PMID- 28743904
TI  - Dietary acrylamide exposure was associated with mild cognition decline among non
      smoking Chinese elderly men.
AB  - The aim of the study is to explore the longitudinal association of dietary
      acrylamide exposure with cognitive performance in Chinese elderly. The analysis
      was conducted among 2534 non-smoking elderly men and women based on a prospective
      study, Mr. and Ms. OS Hong Kong. Dietary acrylamide intake was assessed by food
      frequency questionnaires with data on local food contamination, derived from the
      first Hong Kong Total Diet Study. Global cognitive function was assessed by
      Cantonese version of Mini-Mental State Exam (MMSE) at the baseline and the 4th
      year of follow-up. Multivariable-adjusted linear and logistic regression models
      were used to assess the associations of dietary acrylamide with MMSE score
      changes or risk of poor cognition. The results indicated that among men with MMSE
      >= 18, each one SD increase of acrylamide decreased MMSE score by 7.698% (95%CI: 
      14.943%, -0.452%; p = 0.037). Logistic regression revealed an increased risk of
      poor cognition (MMSE <= 26) in men with HR of 3.356 (1.064~10.591, p = 0.039).
      The association became non-significance after further adjustment for telomere
      length. No significant association was observed in women. Dietary acrylamide
      exposure was associated with a mild cognitive decline or increased risk of poor
      cognition over a 4-year period in non-smoking Chinese elderly men.

PMID- 28743905
TI  - Primitive erythrocytes are generated from hemogenic endothelial cells.
AB  - Primitive erythroblasts are the first blood cells generated during embryonic
      hematopoiesis. Tracking their emergence both in vivo and in vitro has remained
      challenging due to the lack of specific cell surface markers. To selectively
      investigate primitive erythropoiesis, we have engineered a new transgenic
      embryonic stem (ES) cell line, where eGFP expression is driven by the regulatory
      sequences of the embryonic betaH1 hemoglobin gene expressed specifically in
      primitive erythroid cells. Using this ES cell line, we observed that the first
      primitive erythroblasts are detected in vitro around day 1.5 of blast colony
      differentiation, within the cell population positive for the early hematopoietic
      progenitor marker CD41. Moreover, we establish that these eGFP+ cells emerge from
      a hemogenic endothelial cell population similarly to their definitive
      hematopoietic counterparts. We further generated a corresponding betaH1-eGFP
      transgenic mouse model and demonstrated the presence of a primitive erythroid
      primed hemogenic endothelial cell population in the developing embryo. Taken
      together, our findings demonstrate that both in vivo and in vitro primitive
      erythrocytes are generated from hemogenic endothelial cells.

PMID- 28743906
TI  - Transient regulation of three clustered tomato class-I small heat-shock chaperone
      genes by ethylene is mediated by SlMADS-RIN transcription factor.
AB  - Clustered class-I small heat-shock protein (sHSP) chaperone genes, SlHSP17.6,
      SlHSP20.0 and SlHSP20.1, in tomato are demonstrated to be transcriptionally
      regulated by ethylene during mature green (MG) fruit transition into ripening.
      These genes are constitutively expressed at MG fruit stage in two different
      tomato genotypes as well as in their ripening mutants, including rin, nor and Nr,
      and an ethylene-deficient transgenic line, ACS2-antisense. Notably, ethylene
      treatment of the MG fruit led to significant sHSP gene suppression in both wild
      types, ACS2-antisense, nor/nor and Nr/Nr, but not the rin/rin mutant. Inability
      of ethylene to suppress sHSP genes in rin/rin mutant, which harbors MADS-RIN gene
      mutation, suggests that MADS-RIN transcription factor regulates the expression of
      these genes. Treatment of the wild type and ACS2-antisense fruit with the
      ethylene-signaling inhibitor, 1-methylcyclopropane (1-MCP), reversed the sHSP
      gene suppression. Transcripts of representative ethylene-responsive and ripening
      modulated genes confirmed and validated sHSP transcript profile patterns. In
      silico analysis in conjunction with chromatin immunoprecipitation demonstrated
      MADS-RIN protein binding to specific CArG motifs present in the promoters of
      these chaperone genes. The results establish MADS-RIN protein as a
      transcriptional regulator of these chaperone genes in an ethylene-dependent
      manner, and that MADS-RIN protein-regulation of sHSPs is integral to tomato fruit
      ripening.

PMID- 28743907
TI  - Long-term (2-5 years) adverse clinical outcomes associated with ZES versus SES,
      PES and EES: A Meta-Analysis.
AB  - Several previously published trials comparing Zotarolimus Eluting Stents (ZES)
      with Sirolimus Eluting Stents (SES), Paclitaxel Eluting Stents (PES) or
      Everolimus Eluting Stents (EES) at a follow up period of 1 year, were continually
      being followed up in order to assess the long-term outcomes. In this meta
      analysis, we aimed to compare the long-term (2-5 years) adverse clinical outcomes
      which were associated with ZES versus SES, PES and EES following Percutaneous
      Coronary Intervention (PCI). Risk Ratios (RR) with 95% Confidence Intervals (CIs)
      were generated and the analysis was carried out by the RevMan 5.3 software. In
      this analysis with a total number of 17,606 participants, ZES and EES were
      associated with similar adverse outcomes including Stent Thrombosis (ST),
      myocardial infarction (MI), major adverse cardiac events and repeated
      revascularization. When ZES were compared with SES and PES during the long-term,
      MI and definite or probable ST were significantly lower with ZES, with RR: 1.35,
      95% CI: 1.17-1.56; P = 0.0001 and RR: 1.91, 95% CI: 1.33-2.75; P = 0.0004
      respectively whereas the other adverse outcomes were similarly manifested. Future
      research should be able to confirm this hypothesis.

PMID- 28743908
TI  - Multiview three-dimensional reconstruction by millimetre-wave portable camera.
AB  - Millimetre-wave imaging is a powerful non-destructive inspection technique which
      has become widely used in areas such as through-the-wall imaging or concealed
      weapon detection. Nevertheless, current systems are usually limited to either a
      single view point providing a limited 3D millimeter-wave model or a multiview
      relying on the accurate movement of a robot arm through precise positions
      resulting in very bulky systems. In this paper, we present a set of techniques to
      achieve a multiview millimetre-wave scanner. The aperture of the scanner is kept
      below 16 cm so it can be portable and, consequently, multiview can be achieved by
      simple hand movements. In addition, optical images are also acquired with a two
      fold purpose: i) building a complementary 3D-model by employing Structure from
      Movement (SfM) techniques; ii) estimating the scanner position and poses. The
      proposed technology is illustrated for people screening, proving the capacity of
      the system to detect hidden weapons.

PMID- 28743909
TI  - Tonoplast-localized nitrate uptake transporters involved in vacuolar nitrate
      efflux and reallocation in Arabidopsis.
AB  - A great proportion of nitrate taken up by plants is stored in vacuoles. Vacuolar
      nitrate accumulation and release is of great importance to nitrate reallocation
      and efficient utilization. However, how plants mediate nitrate efflux from
      vacuoles to cytoplasm is largely unknown. The current study identified NPF5.11,
      NPF5.12 and NPF5.16 as vacuolar nitrate efflux transporters in Arabidopsis.
      Histochemical analysis showed that NPF5.11, NPF5.12 and NPF5.16 were expressed
      preferentially in root pericycle cells and xylem parenchyma cells, and further
      analysis showed that these proteins were tonoplast-localized. Functional
      characterization using cRNA-injected Xenopus laevis oocytes showed that NPF5.11,
      NPF5.12 and NPF5.16 were low-affinity, pH-dependent nitrate uptake transporters.
      In npf5.11 npf5.12 npf5.16 triple mutant lines, more root-fed 15NO3- was
      translocated to shoots compared to the wild type control. In the NPF5.12
      overexpression lines, proportionally less nitrate was maintained in roots. These
      data together suggested that NPF5.11, NPF5.12 and NPF5.16 might function to
      uptake nitrate from vacuoles into cytosol, thus serving as important players to
      modulate nitrate allocation between roots and shoots.

PMID- 28743910
TI  - Characterization of a Propionibacterium acnes Surface Protein as a Fibrinogen
      Binding Protein.
AB  - Propionibacterium acnes (P. acnes) is a major skin-associated bacterium that was
      long considered commensal, until several studies revealed it to be an
      opportunistic pathogen. We investigated the ability of P. acnes surface proteins
      to recognize ECM proteins and showed that a 58 kDa P. acnes surface protein was
      specifically recognized by human fibrinogen (hFg). The 58 kDa protein was further
      characterized by two-dimensional (2-D) electrophoresis and MALDI-ToF as a P.
      acnes host cell-surface attachment protein, PA25957, recognizing dermatan sulfate
      (DsA1). This protein sequence contains 432 amino acids with the presence of three
      structurally different domains: an N-terminal signal peptide, a C-terminal LPXTG
      motif, and a PT repeat region. DsA1 is mostly produced during stationary phase.
      It appears to be highly glycosylated, containing GalNAc residues. Purified DsA1
      strongly recognizes the Aalpha and Bbeta subunits of hFg, and specific enzymatic
      deglycosylation of hFg demonstrated the involvement of the protein backbone in
      the recognition process. The Bbeta subunit of hFg was cloned in four peptide
      fractions (Fg1-Fg4). The N-terminal Fg1 peptide of hFg was recognized by DsA1,
      and priming DsA1 with Fg1 inhibited DsA1/hFg recognition. We describe here for
      the first time, the characterization of a P. acnes surface glycoprotein
      recognizing human fibrinogen.

PMID- 28743911
TI  - Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via
      mTOR/p70S6K1 signaling.
AB  - Anion exchanger 2 (AE2, encoded by SLC4A2) is a sodium-independent
      chloride/bicarbonate transporter and implicated in the regulation of
      intracellular pH and membrane potential. Previous studies have linked AE2 to the
      tumorigenesis of various cancers. Here, AE2 was identified as an up-regulated
      protein in ovarian cancer tissues compared to adjacent non-tumor lesions based on
      quantitative proteomics analysis. AE2 mRNA was also overexpressed in human
      ovarian cancer samples, and that AE2 overexpression correlated with the shortened
      survival time of ovarian cancer patients. Short-hairpin RNA-mediated knockdown of
      AE2 in A2780 and SK-OV-R3 cells inhibited cell growth and induced cell cycle G1
      phase arrest. In nude mice, its stable knockdown inhibited the tumorigenicity of
      A2780 cells. Gene set enrichment analysis on The Cancer Genome Atlas dataset
      identified that the cell cycle process and mTOR pathway were correlatively with
      the AE2 expression. Expression of key regulators of G1/S transition (Cyclin D1
      and CDK4), and phosphorylation levels of p70S6K were notably reduced in AE2
      knockdown cells. Moreover, experiments with mTOR inhibitor suggested that AE2 may
      promote cell cycle progression through mTOR/p70S6K1 pathway. Together, our
      results suggest up-regulated AE2 promotes ovarian cancer tumorigenesis by
      activating mTOR/p70S6K1 pathway and implicate the potential application of AE2 in
      cancer therapy.

PMID- 28743912
TI  - Structural basis for dolichylphosphate mannose biosynthesis.
AB  - Protein glycosylation is a critical protein modification. In biogenic membranes
      of eukaryotes and archaea, these reactions require activated mannose in the form
      of the lipid conjugate dolichylphosphate mannose (Dol-P-Man). The membrane
      protein dolichylphosphate mannose synthase (DPMS) catalyzes the reaction whereby
      mannose is transferred from GDP-mannose to the dolichol carrier Dol-P, to yield
      Dol-P-Man. Failure to produce or utilize Dol-P-Man compromises organism
      viability, and in humans, several mutations in the human dpm1 gene lead to
      congenital disorders of glycosylation (CDG). Here, we report three high
      resolution crystal structures of archaeal DPMS from Pyrococcus furiosus, in
      complex with nucleotide, donor, and glycolipid product. The structures offer
      snapshots along the catalytic cycle, and reveal how lipid binding couples to
      movements of interface helices, metal binding, and acceptor loop dynamics to
      control critical events leading to Dol-P-Man synthesis. The structures also
      rationalize the loss of dolichylphosphate mannose synthase function in dpm1
      associated CDG.The generation of glycolipid dolichylphosphate mannose (Dol-P-Man)
      is a critical step for protein glycosylation and GPI anchor synthesis. Here the
      authors report the structure of dolichylphosphate mannose synthase in complex
      with bound nucleotide and donor to provide insight into the mechanism of Dol-P
      Man synthesis.

PMID- 28743913
TI  - MicroRNA-200b regulates distal airway development by maintaining epithelial
      integrity.
AB  - miR-200b plays a role in epithelial-to-mesenchymal transition (EMT) in cancer. We
      recently reported abnormal expression of miR-200b in the context of human
      pulmonary hypoplasia in congenital diaphragmatic hernia (CDH). Smaller lung size,
      a lower number of airway generations, and a thicker mesenchyme characterize
      pulmonary hypoplasia in CDH. The aim of this study was to define the role of miR
      200b during lung development. Here we show that miR-200b-/- mice have abnormal
      lung function due to dysfunctional surfactant, increased fibroblast-like cells
      and thicker mesenchyme in between the alveolar walls. We profiled the lung
      transcriptome in miR-200b-/- mice, and, using Gene Ontology analysis, we
      determined that the most affected biological processes include cell cycle,
      apoptosis and protein transport. Our results demonstrate that miR-200b regulates
      distal airway development through maintaining an epithelial cell phenotype. The
      lung abnormalities observed in miR-200b-/- mice recapitulate lung hypoplasia in
      CDH.

PMID- 28743914
TI  - Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates
      Proinflammatory Responses Distinctly from STING Activation.
AB  - Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I
      interferons. However, whether cGAMP plays any roles in regulating metabolic
      homeostasis remains unknown. Here we show that exogenous cGAMP ameliorates
      obesity-associated metabolic dysregulation and uniquely alters proinflammatory
      responses. In obese mice, treatment with cGAMP significantly decreases diet
      induced proinflammatory responses in liver and adipose tissues and ameliorates
      metabolic dysregulation. Strikingly, cGAMP exerts cell-type-specific anti
      inflammatory effects on macrophages, hepatocytes, and adipocytes, which is
      distinct from the effect of STING activation by DMXAA on enhancing
      proinflammatory responses. While enhancing insulin-stimulated Akt phosphorylation
      in hepatocytes and adipocytes, cGAMP weakens the effects of glucagon on
      stimulating hepatocyte gluconeogenic enzyme expression and glucose output and
      blunts palmitate-induced hepatocyte fat deposition in an Akt-dependent manner.
      Taken together, these results suggest an essential role for cGAMP in linking
      innate immunity and metabolic homeostasis, indicating potential applications of
      cGAMP in treating obesity-associated inflammatory and metabolic diseases.

PMID- 28743915
TI  - Platelet behaviour on von Willebrand Factor changes in pregnancy: Consequences of
      haemodilution and intrinsic changes in platelet function.
AB  - Platelet function in pregnancy is poorly understood. Previous studies of platelet
      function in pregnancy have used non-physiological assays of platelet function
      with conflicting results. This study using a physiological assay of platelet
      function investigated platelet interactions with von Willebrand Factor (VWF) in
      blood from healthy pregnant women and healthy non-pregnant controls. Blood
      samples (200 ul) from third-trimester pregnancies (n = 21) and non-pregnant
      controls (n = 21) were perfused through custom-made parallel-plate flow chambers
      coated with VWF under arterial shear (1,500 s-1). Multi-parameter measurements of
      platelet interactions with the immobilized VWF surface were recorded by digital
      image microscopy and analysed using custom-designed platelet-tracking software.
      Platelet interactions with VWF decreased in healthy third-trimester pregnant
      participants relative to controls. This effect is most likely due to
      haemodilution which occurs physiologically during pregnancy. Interestingly,
      platelets in blood from pregnant participants translocated more slowly on VWF
      under arterial-shear conditions. These decreases in platelet translocation speed
      were independent of haemodilution, suggesting intrinsic changes in platelet
      function with pregnancy.

PMID- 28743916
TI  - Analysis of somatic mutations across the kinome reveals loss-of-function
      mutations in multiple cancer types.
AB  - In this study we use somatic cancer mutations to identify important functional
      residues within sets of related genes. We focus on protein kinases, a superfamily
      of phosphotransferases that share homologous sequences and structural motifs and
      have many connections to cancer. We develop several statistical tests for
      identifying Significantly Mutated Positions (SMPs), which are positions in an
      alignment with mutations that show signs of selection. We apply our methods to
      21,917 mutations that map to the alignment of human kinases and identify 23 SMPs.
      SMPs occur throughout the alignment, with many in the important A-loop region,
      and others spread between the N and C lobes of the kinase domain. Since mutations
      are pooled across the superfamily, these positions may be important to many
      protein kinases. We select eleven mutations from these positions for functional
      validation. All eleven mutations cause a reduction or loss of function in the
      affected kinase. The tested mutations are from four genes, including two tumor
      suppressors (TGFBR1 and CHEK2) and two oncogenes (KDR and ERBB2). They also
      represent multiple cancer types, and include both recurrent and non-recurrent
      events. Many of these mutations warrant further investigation as potential cancer
      drivers.

PMID- 28743917
TI  - A rapid, low-cost, and microfluidic chip-based system for parallel identification
      of multiple pathogens related to clinical pneumonia.
AB  - An air-insulated microfluidic chip was designed for the automatic centrifugal
      distribution of samples to 24-test cells, enabling the parallel identification of
      multiple clinical pneumonia-related pathogens in 1.45-MUL reactions without cross
      contamination in 45 min. A portable nucleic acid analyzer that integrates
      mechanical, confocal optical, electronic, and software functions was also
      developed to collect fluorescence data in a O3 mm imaging field near the optical
      diffraction limit for highly sensitive fluorescence detection of nucleic acid
      amplification in real time. This microfluidic chip-based portable nucleic acid
      analyzer could detect low abundance nucleic acids present at as few as 10 copies.
      In a blinded experiment, specific identification of Mycoplasma pneumoniae,
      Staphylococcus aureus, and methicillin-resistant S. aureus was achieved with 229
      clinical patient sputum samples. The total coincidence rate of our system and
      traditional RT-PCR with an ABI 7500 was 99.56%. Four samples accounting for the
      0.44% inconformity were retested by gene sequencing, revealing that our system
      reported the correct results. This novel microfluidic chip-based detection system
      is cost-effective, rapid, sensitive, specific, and has a relatively high
      throughput for parallel identification, which is especially suitable for resource
      limited facilities/areas and point-of-care testing.

PMID- 28743918
TI  - Active Tuberculosis Incidence and Characteristics in Patients Treated with Tumor
      Necrosis Factor Antagonists According to Latent Tuberculosis Infection.
AB  - This study aimed to determine the incidence and characteristics of active
      tuberculosis (TB) in patients treated with tumor necrosis factor (TNF)
      antagonists according to baseline latent tuberculosis infection (LTBI). Data were
      retrospectively obtained from 702 patients aged >=20 years treated with TNF
      antagonists between November 2005 and June 2016 at Severance Hospital, a tertiary
      referral hospital in Seoul, South Korea. The interferon-gamma release assay
      (IGRA) with or without a tuberculin skin test (TST) was used to diagnose LTBI. Of
      the total of 702 patients, LTBI was diagnosed in 255 (36.3%) patients. 23.9%
      (168/702) had positive IGRA results, and 32.2% (165/512) had positive TST
      results. Five patients developed active TB after LTBI treatment, and 6 developed
      TB despite baseline negative LTBI results. After adjustment for age and sex, the
      standardized TB incidence ratio was 6.01 (95% CI 1.94-14.04) in the LTBI group
      and 5.14 (95% CI 1.88-11.18) in the baseline negative LTBI group. Clinicians
      should be aware of the risk of active TB in patients treated with TNF antagonists
      despite baseline negative LTBI screening results. Regular monitoring and serial
      tests should be considered during long-term TNF antagonist therapy, especially in
      intermediate to high TB burden country.

PMID- 28743919
TI  - Highly Flexible and Efficient Fabric-Based Organic Light-Emitting Devices for
      Clothing-Shaped Wearable Displays.
AB  - Recently, the role of clothing has evolved from merely body protection,
      maintaining the body temperature, and fashion, to advanced functions such as
      various types of information delivery, communication, and even augmented reality.
      With a wireless internet connection, the integration of circuits and sensors, and
      a portable power supply, clothes become a novel electronic device. Currently, the
      information display is the most intuitive interface using visualized
      communication methods and the simultaneous concurrent processing of inputs and
      outputs between a wearer and functional clothes. The important aspect in this
      case is to maintain the characteristic softness of the fabrics even when
      electronic devices are added to the flexible clothes. Silicone-based light
      emitting diode (LED) jackets, shirts, and stage costumes have started to appear,
      but the intrinsic stiffness of inorganic semiconductors causes wearers to feel
      discomfort; thus, it is difficult to use such devices for everyday purposes. To
      address this problem, a method of fabricating a thin and flexible emitting fabric
      utilizing organic light-emitting diodes (OLEDs) was developed in this work. Its
      flexibility was evaluated, and an analysis of its mechanical bending
      characteristics and tests of its long-term reliability were carried out.

PMID- 28743920
TI  - Sexual pair-formation in a cicada mediated by acoustic behaviour of females and
      positive phonotaxis of males.
AB  - The functions of female song found in a few cicadas have rarely been studied. In
      the cicada Subpsaltria yangi we investigated the acoustic behaviour and signal
      structure of songs produced by females, the phonotaxis of males, and mate choice,
      as well as the selective pressure imposed on this species by predators. Pair
      formation in S. yangi occurs when males signal, females respond, then males move
      to signaling females, which is opposite to that in most other cicadas where
      females move to calling males. Females only mate once and are sexually
      unreceptive after copulation. Most males mate once, but ~25% mate multiply.
      Females display little direct evidence of mate preference or choice of males, and
      all mate encounters led to a successful mating. Only males are attacked by a
      robber fly, Philonicus albiceps, while flying to females. This imposes strong
      selection on males - only males who can evade predators mate. Males are also
      attracted to human simulations of female calls. This behaviour exposes the mating
      system to impacts from anthropogenic noise systems which could disrupt mating
      activity of this species. Our results improve the understanding of mate
      choice/competition in cicadas, and are valuable for future studies of the
      evolution of sound communication in the Cicadoidea.

PMID- 28743921
TI  - Genetic Susceptibility to Rotavirus Gastroenteritis and Vaccine Effectiveness in
      Taiwanese Children.
AB  - The genetic susceptibility to and vaccine effectiveness against rotavirus
      gastroenteritis were different in distinct ethnic groups. The case-control study
      was aimed to evaluate the effectiveness of rotavirus vaccines and associations
      between the histo-blood group antigens and susceptibility to rotavirus infections
      in a Taiwanese population. Cases were children <18 years old who were
      hospitalized because of laboratory-confirmed rotavirus infection. Controls were
      healthy children matched to cases by age and gender. The secretor status and
      Lewis antigen and ABO types were determined by molecular methods. A total of 68
      cases and 133 controls were included. Rotavirus immunization was recorded in 8
      (12%) cases and 77 (58%) controls, indicating a vaccine effectiveness of 90.3%
      (95% confidence interval [CI], 78.1% - 95.7%). The secretor and Lewis-positive
      genotypes were independently associated with increased risk of rotavirus
      infections (matched odds ratio [mOR] 28.5, 95% CI 2.94-277, P = 0.003 and mOR
      16.8, 95% CI 1.08-2601, P = 0.04, respectively). The distribution of ABO blood
      types did not differ significantly between cases and controls (P = 0.47). In
      conclusion, Taiwanese children with the secretor genotype and Lewis-positive
      genotype were at increased risk of moderate-to-severe rotavirus infections. The
      illness can be effectively prevented by immunization in this population.

PMID- 28743922
TI  - Prevalence of Stroke and Vascular Risk Factors in China: a Nationwide Community
      based Study.
AB  - We aimed to investigate the prevalence of stroke and related vascular risk
      factors in adult population aged 40 years and older in China. We conducted a
      prospective cross-sectional survey in nationally representative sample of 207323
      individuals from all 31 Chinese provinces in 2013. Data were used to analyze the
      prevalence of stroke by age, sex, geographical regions and educational level. The
      age-standardized prevalence of stroke was significantly higher in men than in
      women in all age groups (P < 0.001). The age-standardized prevalence of stroke
      was significantly higher in rural than in urban residents among both men and
      women (P < 0.001). The prevalence of stroke was inversely associated with
      educational level. There were striking geographical variations in stroke
      prevalence in China with a higher prevalence of stroke in northern provinces as
      compared with southern provinces of the country. The age-standardized prevalence
      of hypertension, diabetes, dyslipidemia, atrial fibrillation and obesity in the
      Chinese population aged 40 years and older were 35.24%, 9.55%, 58.72%, 1.57% and
      4.09%, respectively. Stroke and related vascular risk factors remains a major
      public threat in China and effective primary preventive strategies that aimed at
      reducing the burden of stroke and its risk factors are urgently needed.

PMID- 28743923
TI  - Transformation-induced changes in the DNA-nuclear matrix interface, revealed by
      high-throughput analysis of DNA halos.
AB  - In higher eukaryotic nuclei, DNA is periodically anchored to an extraction
      resistant protein structure, via matrix attachment regions. We describe a refined
      and accessible method to non-subjectively, rapidly and reproducibly measure both
      size and stability of the intervening chromatin loops, and use it to demonstrate
      that malignant transformation compromises the DNA-nuclear matrix interface.

PMID- 28743924
TI  - Structure of Chorismate Mutase-like Domain of DAHPS from Bacillus subtilis
      Complexed with Novel Inhibitor Reveals Conformational Plasticity of Active Site.
AB  - 3-deoxy-D-arabino-heptulosonate-7-phosphate-synthase (DAHPS) is the first enzyme
      of the shikimate pathway and is responsible for the synthesis of aromatic amino
      acids in microorganisms. This pathway is an attractive target for antimicrobial
      drugs. In Bacillus subtilis, the N-terminal domain of the bifunctional DAHPS
      enzyme belongs to an AroQ class of chorismate mutase and is functionally
      homologous to the downstream AroH class chorismate mutase. This is the first
      structure of chorismate mutase, AroQ (BsCM_2) enzyme from Bacillus subtilis in
      complex with citrate and chlorogenic acid at 1.9 A and 1.8 A resolution,
      respectively. This work provides the structural basis of ligand binding into the
      active site of AroQ class of chorismate mutase, while accompanied by the
      conformational flexibility of active site loop. Molecular dynamics results showed
      that helix H2' undergoes uncoiling at the first turn and increases the mobility
      of loop L1'. The side chains of Arg45, Phe46, Arg52 and Lys76 undergo
      conformational changes, which may play an important role in DAHPS regulation by
      the formation of the domain-domain interface. Additionally, binding studies
      showed that the chlorogenic acid binds to BsCM_2 with a higher affinity than
      chorismate. These biochemical and structural findings could lead to the
      development of novel antimicrobial drugs.

PMID- 28743925
TI  - Bimanual grasping does not adhere to Weber's law.
AB  - According to Weber's law, a fundamental principle of perception, visual
      resolution decreases in a linear fashion with an increase in object size.
      Previous studies have shown, however, that unlike for perception, grasping does
      not adhere to Weber's law. Yet, this research was limited by the fact that
      perception and grasping were examined for a restricted range of stimulus sizes
      bounded by the maximum fingers span. The purpose of the current study was to test
      the generality of the dissociation between perception and action across a
      different type of visuomotor task, that of bimanual grasping. Bimanual grasping
      also allows to effectively measure visual resolution during perception and action
      across a wide range of stimulus sizes compared to unimanual grasps. Participants
      grasped or estimated the sizes of large objects using both their hands. The
      results showed that bimanual grasps violated Weber's law throughout the entire
      movement trajectory. In contrast, Just Noticeable Differences (JNDs) for
      perceptual estimations of the objects increased linearly with size, in agreement
      with Weber's law. The findings suggest that visuomotor control, across different
      types of actions and for a large range of size, is based on absolute rather than
      on relative representation of object size.

PMID- 28743926
TI  - Inactivation of DNase1L2 and DNase2 in keratinocytes suppresses DNA degradation
      during epidermal cornification and results in constitutive parakeratosis.
AB  - The stratum corneum of the epidermis constitutes the mammalian skin barrier to
      the environment. It is formed by cornification of keratinocytes, a process which
      involves the removal of nuclear DNA. Here, we investigated the mechanism of
      cornification-associated DNA degradation by generating mouse models deficient of
      candidate DNA-degrading enzymes and characterizing their epidermal phenotypes. In
      contrast to Dnase1l2 -/- mice and keratinocyte-specific DNase2 knockout mice
      (Dnase2 Deltaep ), Dnase1l2 -/- Dnase2 Deltaep mice aberrantly retained nuclear
      DNA in the stratum corneum, a phenomenon commonly referred to as parakeratosis.
      The DNA within DNase1L2/DNase2-deficient corneocytes was partially degraded in a
      DNase1-independent manner. Isolation of corneocytes, i.e. the cornified cell
      components of the stratum corneum, and labelling of DNA demonstrated that
      corneocytes of Dnase1l2 -/- Dnase2 Deltaep mice contained DNA in a nucleus-shaped
      compartment that also contained nucleosomal histones but lacked the nuclear
      intermediate filament protein lamin A/C. Parakeratosis was not associated with
      altered corneocyte resistance to mechanical stress, changes in transepidermal
      water loss, or inflammatory infiltrates in Dnase1l2 -/- Dnase2 Deltaep mice. The
      results of this study suggest that cornification of epidermal keratinocytes
      depends on the cooperation of DNase1L2 and DNase2 and indicate that parakeratosis
      per se does not suffice to cause skin pathologies.

PMID- 28743927
TI  - Solid-State 77Se NMR of Organoselenium Compounds through Cross Polarization Magic
      Angle Spinning (CPMAS) Method.
AB  - Characterization of selenium states by 77Se NMR is quite important to provide
      vital information for mechanism studies in organoselenium-catalyzed reactions.
      With the development of heterogeneous polymer-supported organoselenium catalysts,
      the solid state 77Se NMR comes to the spotlight. It is necessary to figure out an
      advanced protocol that provides good quality spectra within limited time because
      solid state 77Se NMR measurements are always time consuming due to the long
      relaxation time and the relatively low sensitivity. Studies on small molecules
      and several novel polymer-supported organoselenium materials in this article
      showed that cross polarization (CP) method with the assistance of magic angle
      spinning (MAS) was more efficient to get high quality spectra than the methods by
      using single pulse (SP) or high power 1H decoupling (HPHD) combined with MAS.
      These results lead to a good understanding of the effect of the molecular
      structure, the heteronuclear coupling, the long-range ordering of the solid
      (crystal or amorphous), and the symmetry of 77Se on quality of their spectra.

PMID- 28743928
TI  - Effect of probiotics on the meat flavour and gut microbiota of chicken.
AB  - To date, no report has demonstrated the use of beneficial microbes for
      contributing to the flavour characteristics and gut microbiota diversity of
      chicken. Here, we selected six probiotics obtained from our laboratory and
      supplemented them in six different combinations to 420 newborn male Qingjiaoma
      chickens under the same controlled living environment (60 birds, no probiotic
      supplements). The results showed that chicken supplemented with Bacillus species
      showed beneficial effects in body weight. Acetate is the major fermentation
      production in the chicken caecum, and chicken supplemented with Pediococcus
      pentosaceus had the average higher short chain fatty acids (SCFAs) contents. In
      chicken caecal microflora, the abundance of Bacteroidetes bacteria was positively
      correlated with the content of propionate, butyrate, and isobutyrate, whereas an
      increase in acetate content was positively correlated to the abundance of
      Firmicutes. Compared to chickens without probiotic supplement, chickens
      supplemented with P. pentosaceus had more characteristic flavour compounds in the
      sampled breast meat, especially higher concentrations of (E)-2-heptenal, (E,E)
      2,4-nonadienal, and certain C6-C9 unsaturated fatty acids. This resulted in a
      stronger chicken-fatty or fatty odour which directly improved the flavour. These
      findings suggest that probiotics can improve chicken meat flavour and increase
      gut microbiota diversity.

PMID- 28743929
TI  - 3D semiconducting nanostructures via inverse lipid cubic phases.
AB  - Well-ordered and highly interconnected 3D semiconducting nanostructures of
      bismuth sulphide were prepared from inverse cubic lipid mesophases. This route
      offers significant advantages in terms of mild conditions, ease of use and
      electrode architecture over other routes to nanomaterials synthesis for device
      applications. The resulting 3D bicontinous nanowire network films exhibited a
      single diamond topology of symmetry Fd3m (Q227) which was verified by Small angle
      X-ray scattering (SAXS) and Transmission electron microscopy (TEM) and holds
      great promise for potential applications in optoelectronics, photovoltaics and
      thermoelectrics.

PMID- 28743930
TI  - Full-length cloning, sequence analysis and expression detection of the beta
      tubulin gene from the Chinese gall aphid (Schlechtendalia chinensis).
AB  - Some insect galls are formed on sumac plants by certain aphid species and have
      been used for medicinal and chemical purposes as they are rich in tannins. The
      most prominent species among gall aphids in China is Schlechtendalia chinensis,
      which formed horn-shaped galls on the winged rachis of Rhus chinensis. S.
      chinensis has a complex life cycle, with a switch of hosts between R. chinensis
      and certain mosses, and a switch of sexual and asexual reproduction (cyclical
      parthenogenesis). We have cloned a full-length cDNA of the beta-tubulin gene from
      S. chinensis, using qPCR and RACE. This cDNA has 1606 base pairs with a 251 bp 5'
      untranslated region (5'-UTR) and a 15 bp 3'-untranslated region (3'-UTR). The
      gene encodes a protein with 376 amino acids residues. The expression levels of
      the beta-tubulin gene in S. chinensis were investigated among fundatrigeniae and
      overwintering larvae rearing under either natural conditions, or at 7.5  degrees
      C and 18  degrees C. No significant differences (P > 0.01) in gene expression
      levels were found in insects under these conditions. It is indicates that the
      beta-tubulin gene is highly conserved and then it may be used as a reference for
      further research in gene expression and reproduction determination in this
      important aphid.

PMID- 28743931
TI  - Topological Heat Transport and Symmetry-Protected Boson Currents.
AB  - The study of non-equilibrium properties in topological systems is of practical
      and fundamental importance. Here, we analyze the stationary properties of a two
      dimensional bosonic Hofstadter lattice coupled to two thermal baths in the
      quantum open-system formalism. Novel phenomena appear like chiral edge heat
      currents that are the out-of-equilibrium counterparts of the zero-temperature
      edge currents. They support a new concept of dissipative symmetry-protection,
      where a set of discrete symmetries protects topological heat currents, differing
      from the symmetry-protection devised in closed systems and zero-temperature.
      Remarkably, one of these currents flows opposite to the decreasing external
      temperature gradient. As the starting point, we consider the case of a single
      external reservoir already showing prominent results like thermal erasure effects
      and topological thermal currents. Our results are experimentally accessible with
      platforms like photonics systems and optical lattices.

PMID- 28743933
TI  - Eliminating viral hepatitis - momentum must keep building.

PMID- 28743932
TI  - Efficient probabilistic inference in generic neural networks trained with non
      probabilistic feedback.
AB  - Animals perform near-optimal probabilistic inference in a wide range of
      psychophysical tasks. Probabilistic inference requires trial-to-trial
      representation of the uncertainties associated with task variables and subsequent
      use of this representation. Previous work has implemented such computations using
      neural networks with hand-crafted and task-dependent operations. We show that
      generic neural networks trained with a simple error-based learning rule perform
      near-optimal probabilistic inference in nine common psychophysical tasks. In a
      probabilistic categorization task, error-based learning in a generic network
      simultaneously explains a monkey's learning curve and the evolution of
      qualitative aspects of its choice behavior. In all tasks, the number of neurons
      required for a given level of performance grows sublinearly with the input
      population size, a substantial improvement on previous implementations of
      probabilistic inference. The trained networks develop a novel sparsity-based
      probabilistic population code. Our results suggest that probabilistic inference
      emerges naturally in generic neural networks trained with error-based learning
      rules.Behavioural tasks often require probability distributions to be inferred
      about task specific variables. Here, the authors demonstrate that generic neural
      networks can be trained using a simple error-based learning rule to perform such
      probabilistic computations efficiently without any need for task specific
      operations.

PMID- 28743934
TI  - Many European countries 'flying blind' in their efforts to eliminate viral
      hepatitis.

PMID- 28743935
TI  - Direct-acting antivirals for paediatric HCV: we got there.

PMID- 28743936
TI  - HCV elimination - lessons learned from a small Eurasian country, Georgia.

PMID- 28743937
TI  - Photo-irradiated caffeic acid exhibits antimicrobial activity against
      Streptococcus mutans biofilms via hydroxyl radical formation.
AB  - An antimicrobial technique based on photo-oxidation of caffeic acid (CA) has
      recently been developed, but its effect on biofilm-forming bacteria is unknown.
      The present study aimed to evaluate the effect of photo-irradiated CA against
      Streptococcus mutans (cariogenic bacteria) biofilm as it relates to hydroxyl
      radical formation. S. mutans biofilms grown on hydroxyapatite disks were immersed
      in CA solution (0-2 mg/mL) and irradiated with LED light at wavelengths of 365,
      385, and 400 nm and at irradiances of 500, 1000, and 2000 mW/cm2 for 4 min.
      Biofilm viable bacterial counts were determined by colony counting. The yield of
      hydroxyl radicals generated by the LED irradiation of CA solution was quantified
      by electron spin resonance analysis. Of the conditions tested, the highest
      bactericidal effect, with a > 5-log reduction in viable bacterial counts, was
      obtained by irradiation of a 1 mg/mL CA solution with 385 nm LED and at an
      irradiance of 2000 mW/cm2. Hydroxyl radical formation was related to this
      bactericidal effect. The present study suggests that the antimicrobial technique
      based on the 385 nm LED irradiation of CA is effective against cariogenic
      biofilms and can be applied as an adjunctive chemotherapy for dental caries.

PMID- 28743938
TI  - Lactate provides a strong pH-independent ventilatory signal in the facultative
      air-breathing teleost Pangasianodon hypophthalmus.
AB  - Fish regulate ventilation primarily by sensing O2-levels in the water and
      arterial blood. It is well established that this sensory process involves several
      steps, but the underlying mechanisms remain frustratingly elusive. Here we
      examine the effect of increasing lactate ions at constant pH on ventilation in a
      teleost; specifically the facultative air-breathing catfish Pangasianodon
      hypophthalmus. At lactate levels within the physiological range obtained by Na
      Lactate injections (3.5 +/- 0.8 to 10.9 +/- 0.7 mmol L-1), gill ventilation
      increased in a dose-dependent manner to levels comparable to those elicited by
      NaCN injections (2.0 umol kg-1), which induces a hypoxic response and higher than
      those observed in any level of ambient hypoxia (lowest PO2 = 20 mmHg). High
      lactate concentrations also stimulated air-breathing. Denervation of the first
      gill arch reduced the ventilatory response to lactate suggesting that part of the
      sensory mechanism for lactate is located at the first gill arch. However, since a
      residual response remained after this denervation, the other gill arches or
      extrabranchial locations must also be important for lactate sensing. We propose
      that lactate plays a role as a signalling molecule in the hypoxic ventilatory
      response in fish.

PMID- 28743939
TI  - A Cryosectioning Technique for the Observation of Intracellular Structures and
      Immunocytochemistry of Tissues in Atomic Force Microscopy (AFM).
AB  - The use of cryosectioning facilitates the morphological analysis and
      immunocytochemistry of cells in tissues in atomic force microscopy (AFM). The
      cantilever can access all parts of a tissue sample in cryosections after the
      embedding medium (sucrose) has been replaced with phosphate-buffered saline
      (PBS), and this approach has enabled the production of a type of high-resolution
      image. The images resembled those obtained from freeze-etching replica electron
      microscopy (EM) rather than from thin-section EM. The AFM images showed disks
      stacked and enveloped by the cell membrane in rod photoreceptor outer segments
      (ROS) at EM resolution. In addition, ciliary necklaces on the surface of
      connecting cilium, three-dimensional architecture of synaptic ribbons, and the
      surface of the post-synaptic membrane facing the active site were revealed, which
      were not apparent using thin-section EM. AFM could depict the molecular binding
      of anti-opsin antibodies conjugated to a secondary fluorescent antibody bound to
      the disk membrane. The specific localization of the anti-opsin binding sites was
      verified through correlation with immunofluorescence signals in AFM combined with
      confocal fluorescence microscope. To prove reproducibility in other tissues
      besides retina, cryosectioning-AFM was also applied to elucidate molecular
      organization of sarcomere in a rabbit psoas muscle.

PMID- 28743940
TI  - The burdens of lung cancer involved multiple primary cancers and its occurring
      patterns-SEER Analysis between 1973 and 2006.
AB  - The prognosis of malignancies has improved in recent years, subsequent primary
      cancers (SPCs) have become more frequent. This study investigates the patterns of
      lung cancer involved multiple primary cancers. We enrolled 206,619 primary lung
      cancer patients and 2,071,922 patients with other primary malignancies from
      Surveillance, Epidemiology and End Results (SEER) database. Observed annual risk
      (OAR) and absolute numbers were used to describe the risk of SPC and observed
      cases of SPC per 10,000 person-years at risk. Overall, OAR of SPCs following lung
      cancer was 176.28. At follow-up, 41.26% of SPCs occurred within 12-59 months
      while the highest OAR appeared after 120 months. The overall OAR of subsequent
      lung cancer after other malignancies was 27.90. Overall, the highest OAR and the
      highest absolute numbers of subsequent lung cancers were noticed 60-119 months
      and over 120 months post-diagnosis, respectively. Ten related cancers were
      listed. Our findings encourage surveillance for 10 common SPCs in lung cancer
      survivors during follow-up as well as screening for lung cancer after 10 common
      malignancies.

PMID- 28743941
TI  - Transcriptomes and expression profiling of deep-sea corals from the Red Sea
      provide insight into the biology of azooxanthellate corals.
AB  - Despite the importance of deep-sea corals, our current understanding of their
      ecology and evolution is limited due to difficulties in sampling and studying
      deep-sea environments. Moreover, a recent re-evaluation of habitat limitations
      has been suggested after characterization of deep-sea corals in the Red Sea,
      where they live at temperatures of above 20  degrees C at low oxygen
      concentrations. To gain further insight into the biology of deep-sea corals, we
      produced reference transcriptomes and studied gene expression of three deep-sea
      coral species from the Red Sea, i.e. Dendrophyllia sp., Eguchipsammia fistula,
      and Rhizotrochus typus. Our analyses suggest that deep-sea coral employ
      mitochondrial hypometabolism and anaerobic glycolysis to manage low oxygen
      conditions present in the Red Sea. Notably, we found expression of genes related
      to surface cilia motion that presumably enhance small particle transport rates in
      the oligotrophic deep-sea environment. This is the first study to characterize
      transcriptomes and in situ gene expression for deep-sea corals. Our work offers
      several mechanisms by which deep-sea corals might cope with the distinct
      environmental conditions present in the Red Sea As such, our data provide
      direction for future research and further insight to organismal response of deep
      sea coral to environmental change and ocean warming.

PMID- 28743942
TI  - Covalent, Non-Covalent, Encapsulated Nanodrug Regulate the Fate of Intra- and
      Extracellular Trafficking: Impact on Cancer and Normal Cells.
AB  - Drugs need to be designed to access the designated intracellular organelle
      compartments in order to maximize anticancer efficacy. This study identified that
      covalently conjugated, non-covalent polyethylene glycol coated and encapsulated
      nanodrugs selectively influence drug uptake, the intracellular and extracellular
      trafficking of cancer cells. The types of nano conjugation modulated
      intracellular dynamics associated with differential impact on anti-cancer
      efficacy, but also induced differential cytotoxicity on cancer versus normal
      cells. In conclusion, this study demonstrated the importance of selecting the
      appropriate type of nano-conjugation for delivering organelle specific, active
      chemotherapeutic agents through controlled intracellular trafficking.

PMID- 28743943
TI  - Multiplex Immunoassays Utilizing Differential Affinity Using Aptamers Generated
      by MARAS.
AB  - Disease diagnosis typically requires to determine concentration of multiple
      biomarkers in patient serums. Here, a novel method for multiplex immunoassays is
      proposed and the feasibility is demonstrated. The method utilizes the
      differential affinity between aptamers and multiple analytes for multiplex
      immunoassays. During the selection, aptamers capable of binding to multiple
      analytes with different affinities are screened from a random oligonucleotide
      library using the MARAS procedure with different magnetic field conditions for
      different target analytes. During the detection, the same magnetic field
      conditions are applied to differentiate different target analytes in blind
      serums. The results show that the recovery rates of the spiked targets in BD
      buffer and blind serums are similar. Moreover, there is a minimal interference
      resulting from non-specific binding of molecules in serums other than the target
      molecules. Therefore, the use of differential affinities between aptamers and
      different analytes for multiplex immunoassays is proved to be feasible.

PMID- 28743944
TI  - Temperature tunability of surface plasmon enhanced Smith-Purcell terahertz
      radiation for semiconductor-based grating.
AB  - In this work, the terahertz (THz) Smith-Purcell radiations (SPRs) for the
      relativistic electron bunch passing over an indium antimonide (InSb)-based
      substrate with a subwavelength grating under various temperatures of substrate
      are investigated by FDTD simulations and theoretical analyses. The explored SPR
      is locked and enhanced at a certain emission wavelength with the emission angle
      still following the wavelength-angle relation of the traditional SPR. This
      wavelength agrees with the (vacuum) wavelength of surface plasmons (SPs) at the
      air-InSb interface excited by the electron bunch. The enhancement of SPR at this
      wavelength is attributed to the energy from electron concentrated in the excited
      SPs and then transformed into radiation via the SPR mechanism. When the
      temperature of InSb increases, the emission wavelength of the enhanced SPR
      decreases along with the emission angles increasing gradually. This work
      demonstrates that the emission wavelength and angle of the enhanced SPR from the
      InSb grating can be manipulated by the temperature of InSb. The temperature
      tunability of SP-enhanced SPR has potential applications in the fields of optical
      beam steering and metamaterial light source.

PMID- 28743945
TI  - Lithium Sensitive ORAI1 Expression, Store Operated Ca2+ Entry and Suicidal Death
      of Neurons in Chorea-Acanthocytosis.
AB  - Chorea-Acanthocytosis (ChAc), a neurodegenerative disorder, results from loss-of
      function-mutations of chorein-encoding gene VPS13A. In tumour cells chorein up
      regulates ORAI1, a Ca2+-channel accomplishing store operated Ca2+-entry (SOCE)
      upon stimulation by STIM1. Furthermore SOCE could be up-regulated by lithium. The
      present study explored whether SOCE impacts on neuron apoptosis. Cortical neurons
      were differentiated from induced pluripotent stem cells generated from
      fibroblasts of ChAc patients and healthy volunteers. ORAI1 and STIM1 transcript
      levels and protein abundance were estimated from qRT-PCR and Western blotting,
      respectively, cytosolic Ca2+-activity ([Ca2+]i) from Fura-2-fluorescence, as well
      as apoptosis from annexin-V-binding and propidium-iodide uptake determined by
      flow cytometry. As a result, ORAI1 and STIM1 transcript levels and protein
      abundance and SOCE were significantly smaller and the percentage apoptotic cells
      significantly higher in ChAc neurons than in control neurons. Lithium treatment
      (2 mM, 24 hours) increased significantly ORAI1 and STIM1 transcript levels and
      protein abundance, an effect reversed by inhibition of Serum & Glucocorticoid
      inducible Kinase 1. ORAI1 blocker 2-APB (50 uM, 24 hours) significantly decreased
      SOCE, markedly increased apoptosis and abrogated the anti-apoptotic effect of
      lithium. In conclusion, enhanced neuronal apoptosis in ChAc at least partially
      results from decreased ORAI1 expression and SOCE, which could be reversed by
      lithium treatment.

PMID- 28743946
TI  - Identification of the ESKAPE pathogens by mass spectrometric analysis of
      microbial membrane glycolipids.
AB  - Rapid diagnostics that enable identification of infectious agents improve patient
      outcomes, antimicrobial stewardship, and length of hospital stay. Current methods
      for pathogen detection in the clinical laboratory include biological culture,
      nucleic acid amplification, ribosomal protein characterization, and genome
      sequencing. Pathogen identification from single colonies by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of
      high abundance proteins is gaining popularity in clinical laboratories. Here, we
      present a novel and complementary approach that utilizes essential microbial
      glycolipids as chemical fingerprints for identification of individual bacterial
      species. Gram-positive and negative bacterial glycolipids were extracted using a
      single optimized protocol. Extracts of the clinically significant ESKAPE
      pathogens: E nterococcus faecium, S taphylococcus aureus, K lebsiella pneumoniae,
      A cinetobacter baumannii, P seudomonas aeruginosa, and E nterobacter spp. were
      analyzed by MALDI-TOF-MS in negative ion mode to obtain glycolipid mass spectra.
      A library of glycolipid mass spectra from 50 microbial entries was developed that
      allowed bacterial speciation of the ESKAPE pathogens, as well as identification
      of pathogens directly from blood bottles without culture on solid medium and
      determination of antimicrobial peptide resistance. These results demonstrate that
      bacterial glycolipid mass spectra represent chemical barcodes that identify
      pathogens, potentially providing a useful alternative to existing diagnostics.

PMID- 28743947
TI  - Match between soaring modes of black kites and the fine-scale distribution of
      updrafts.
AB  - Understanding how soaring birds use updrafts at small spatial scales is important
      to identify ecological constraints of movement, and may help to prevent conflicts
      between wind-energy development and the conservation of wildlife. We combined
      high-frequency GPS animal tracking and fine-spatial-scale uplift modelling to
      establish a link between flight behaviour of soaring birds and the distribution
      of updrafts. We caught 21 black kites (Milvus migrans) and GPS-tracked them while
      flying over the Tarifa region, on the Spanish side of the Strait of Gibraltar.
      This region has a diverse topography and land cover, favouring a heterogeneous
      updraft spatial distribution. Bird tracks were segmented and classified into
      flight modes from motion parameters. Thermal and orographic uplift velocities
      were modelled from publically available remote-sensing and meteorological data.
      We found that birds perform circular soaring in areas of higher predicted thermal
      uplift and linear soaring in areas of higher predicted orographic uplift
      velocity. We show that updraft maps produced from publically available data can
      be used to predict where soaring birds will concentrate their flight paths and
      how they will behave in flight. We recommend the use of this methodological
      approach to improve environmental impact assessments of new wind-energy
      installations.

PMID- 28743948
TI  - Realisation of topological zero-energy mode in bilayer graphene in zero magnetic
      field.
AB  - Bilayer graphene (BLG) gapped by a vertical electric field represents a valley
      symmetry-protected topological insulating state. Emergence of a new topological
      zero-energy mode has been proposed in BLG at a boundary between regions of
      inverted band gaps induced by two oppositely polarized vertical electric fields.
      However, its realisation has been challenged by the enormous difficulty in
      arranging two pairs of accurately aligned split gates on the top and bottom
      surfaces of clean BLG. Here we report realisation of the topological zero-energy
      mode in ballistic BLG, with zero-bias differential conductance close to the ideal
      value of 4 e 2/h (e is the electron charge and h is Planck's constant) along a
      boundary channel between a pair of gate-defined inverted band gaps. This
      constitutes the bona fide electrical-gate-tuned generation of a valley-symmetry
      protected topological boundary conducting channel in BLG in zero magnetic field,
      which is essential to valleytronics applications of BLG.

PMID- 28743949
TI  - The Rice Phytochrome Genes, PHYA and PHYB, Have Synergistic Effects on Anther
      Development and Pollen Viability.
AB  - Phytochromes are the main plant photoreceptors regulating multiple developmental
      processes. However, the regulatory network of phytochrome-mediated plant
      reproduction has remained largely unexplored. There are three phytochromes in
      rice, phyA, phyB and phyC. No changes in fertility are observed in the single
      mutants, whereas the seed-setting rate of the phyA phyB double mutant is
      significantly reduced. Histological and cytological analyses showed that the
      reduced fertility of the phyA phyB mutant was due to defects in both anther and
      pollen development. The four anther lobes in the phyA phyB mutant were developed
      at different stages with fewer pollen grains, most of which were aborted. At the
      mature stage, more than one lobe in the double mutant was just consisted of
      several cell layers. To identify genes involved in phytochrome-mediated anther
      development, anther transcriptomes of phyA, phyB and phyA phyB mutants were
      compared to that of wild-type rice respectively. Analysis of 2,241 double-mutant
      specific differentially expressed transcripts revealed that the metabolic
      profiles, especially carbohydrate metabolism, were altered greatly, and heat
      shock responses were activated in the double mutant. This study firstly provides
      valuable insight into the complex regulatory networks underlying phytochrome
      mediated anther and pollen development in plants, and offers novel clues for
      hybrid rice breeding.

PMID- 28743950
TI  - Auditory Neuropathy after Damage to Cochlear Spiral Ganglion Neurons in Mice
      Resulting from Conditional Expression of Diphtheria Toxin Receptors.
AB  - Auditory neuropathy (AN) is a hearing disorder characterized by normal cochlear
      amplification to sound but poor temporal processing and auditory perception in
      noisy backgrounds. These deficits likely result from impairments in auditory
      neural synchrony; such dyssynchrony of the neural responses has been linked to
      demyelination of auditory nerve fibers. However, no appropriate animal models are
      currently available that mimic this pathology. In this study, Cre-inducible
      diphtheria toxin receptor (iDTR +/+ ) mice were cross-mated with mice containing
      Cre (Bhlhb5-Cre +/- ) specific to spiral ganglion neurons (SGNs). In double
      positive offspring mice, the injection of diphtheria toxin (DT) led to a 30-40%
      rate of death for SGNs, but no hair cell damage. Demyelination types of
      pathologies were observed around the surviving SGNs and their fibers, many of
      which were distorted in shape. Correspondingly, a significant reduction in
      response synchrony to amplitude modulation was observed in this group of animals
      compared to the controls, which had a Cre- genotype. Taken together, our results
      suggest that SGN damage following the injection of DT in mice with Bhlhb5-Cre +/-
      and iDTR +/- is likely to be a good AN model of demyelination.

PMID- 28743951
TI  - Genome-wide Analysis and Expression Divergence of the Trihelix family in Brassica
      Rapa: Insight into the Evolutionary Patterns in Plants.
AB  - Trihelix gene family is an important transcription factor (TF) family involved in
      plants' growth and development. This extensive study of trihelix genes from
      Arabidopsis thaliana to Brassica rapa could shed light on the evolution in plants
      and support crop breeding. In this study, a total of 52 trihelix genes were
      identified in B.rapa. Whole-genome annotation, molecular-evolution and gene
      expression analyses of all known trihelix genes were conducted. By statistics of
      the number of trihelix genes in each species, we found the expansion of trihelix
      gene family started with angiosperm evolution. And SIP1 was more preferentially
      retained than other subgroups (GT-1, GT-2, GTgamma, SH4), consistent with the
      gene dosage hypothesis. Then we investigated the evolutionary patterns,
      footprints and conservation of trihelix genes in selected plants. The putative
      trihelix proteins were highly conserved, but their expression patterns varied.
      Half of these genes were highly expressed in all the selected organs but some
      showed tissue-specific expression patterns. Furthermore, among six abiotic
      stresses (Cold, Heat, PEG, NaCl, ABA and GA), most trihelix genes were activated
      by salt and ABA treatment. In summary, the phylogenetic, evolution and expression
      analyses of trihelix gene family in B.rapa establish a solid foundation for
      future comprehensive functional analysis of BraTHs.

PMID- 28743952
TI  - Scaling Relations and Self-Similarity of 3-Dimensional Reynolds-Averaged Navier
      Stokes Equations.
AB  - Scaling conditions to achieve self-similar solutions of 3-Dimensional (3D)
      Reynolds-Averaged Navier-Stokes Equations, as an initial and boundary value
      problem, are obtained by utilizing Lie Group of Point Scaling Transformations. By
      means of an open-source Navier-Stokes solver and the derived self-similarity
      conditions, we demonstrated self-similarity within the time variation of flow
      dynamics for a rigid-lid cavity problem under both up-scaled and down-scaled
      domains. The strength of the proposed approach lies in its ability to consider
      the underlying flow dynamics through not only from the governing equations under
      consideration but also from the initial and boundary conditions, hence allowing
      to obtain perfect self-similarity in different time and space scales. The
      proposed methodology can be a valuable tool in obtaining self-similar flow
      dynamics under preferred level of detail, which can be represented by initial and
      boundary value problems under specific assumptions.

PMID- 28743953
TI  - Detection of the spatial patterns of water storage variation over China in recent
      70 years.
AB  - Terrestrial water storage (TWS) variation is crucial for global hydrological
      cycles and water resources management under climatic changes. In the previous
      studies, changes in water storage of some part of China have been studied with
      GRACE data in recent ten years. However, the spatial pattern of changes in water
      storage over China may be different in a long period. Here, we aimed to present
      long-term spatial patterns of TWS over China between 1948 to 2015 by unique
      Global Land Data Assimilation System Version 2 data and identify possible factors
      to water storage changes. The results revealed that the inner-annual variations
      in TWS of China exhibited remarkable downward trends with decreased rate of 0.1
      cm/yr. Meanwhile, we found that spatial patterns of TWS in China can be divided
      into three distinct sub-regions of TWS region with increased, TWS region with
      decreased, TWS region with insignificant variation. The Northeast had decreased
      trends (-0.05 cm/yr) due to climate change and anthropogenic activities. Urban
      expansion is a non-ignorable factor to TWS reduction in Jing-Jin-Ji region (r =
      0.61); the west had increased from 1948 to 2015 (0.03 cm/yr) due to precipitation
      increased and recharge by glacier melt; the south had insignificant trends and
      TWS varied with precipitation (r = 0.78).

PMID- 28743954
TI  - Molecular diversity of benthic ctenophores (Coeloplanidae).
AB  - Coeloplanidae, the largest family of benthic ctenophores, comprises 33 species,
      all described based on traditional morphological characteristics, such as
      coloration, length, and number of aboral papillae, which are highly variable and
      can be affected by fixation methods and environmental conditions. Thus, there is
      a need for reliable genetic markers to complement the morphological
      identifications at the species level. Here, we analyzed 95 specimens from 11
      morphologically distinct species of benthic ctenophores from the Red Sea and Sulu
      Sea, and tested selected regions of four genetic markers (ITS1, 18S rRNA, 28S
      rRNA and COI) for their ability to differentiate between species. We show that
      the barcoding region of the mitochondrial gene, cytochrome oxidase subunit I
      (COI), is highly variable among species of Coeloplanidae, and effectively
      discriminates between species in this family. The average Kimura-2-parameter
      (K2P) distance between species-level clades was 10%, while intraspecific
      variation was ~30 times lower (0.36%). COI-based phylogeny supported the
      delineation of four recently described new species from the Red Sea. The other
      nuclear markers tested were found to be too conserved in order to separate
      between species. We conclude that COI is a potential molecular barcode for the
      family Coeloplanidae and suggest to test it in pelagic ctenophores.

PMID- 28743955
TI  - Early synaptic dysfunction induced by alpha-synuclein in a rat model of
      Parkinson's disease.
AB  - Evidence suggests that synapses are affected first in Parkinson's disease (PD).
      Here, we tested the claim that pathological accumulation of alpha-synuclein, and
      subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in
      PD. We determined early synaptic changes in rats that overexpress human alpha
      synuclein by local injection of viral-vectors in midbrain. We aimed to achieve
      alpha-synuclein levels sufficient to induce terminal pathology without
      significant loss of nigral neurons. We tested synaptic disruption in vivo by
      analyzing motor defects and binding of a positron emission tomography (PET)
      radioligand to the vesicular monoamine transporter 2, (VMAT2),
      [11C]dihydrotetrabenazine (DTBZ). Animals overexpressing alpha-synuclein had
      progressive motor impairment and, 12 weeks post-surgery, showed asymmetric in
      vivo striatal DTBZ binding. The PET images matched ligand binding in post-mortem
      tissue, and histological markers of dopaminergic integrity. Histology confirmed
      the absence of nigral cell death with concomitant significant loss of striatal
      terminals. Progressive aggregation of proteinase-K resistant and Ser129
      phosphorylated alpha-synuclein was observed in dopaminergic terminals, in
      dystrophic swellings that resembled axonal spheroids and contained mitochondria
      and vesicular proteins. In conclusion, pathological alpha-synuclein in nigro
      striatal axonal terminals leads to early axonal pathology, synaptic disruption,
      dysfunction of dopaminergic neurotransmission, motor impairment, and measurable
      change of VMAT2 in the absence of cell loss.

PMID- 28743956
TI  - Post-hypoxia Invasion of the fetal brain by multidrug resistant Staphylococcus.
AB  - Herein we describe an association between activation of inflammatory pathways
      following transient hypoxia and the appearance of the multidrug resistant
      bacteria Staphylococcus simulans in the fetal brain. Reduction of maternal
      arterial oxygen tension by 50% over 30 min resulted in a subseiuent significant
      over-expression of genes associated with immune responses 24 h later in the fetal
      brain. The activated genes were consistent with stimulation by bacterial
      lipopolysaccharide; an influx of macrophages and appearance of live bacteria were
      found in these fetal brains. S. simulans was the predominant bacterial species in
      fetal brain after hypoxia, but was found in placenta of all animals. Strains of
      S. simulans from the placenta and fetal brain were equally highly resistant to
      multiple antibiotics including methicillin and had identical genome sequences.
      These results suggest that bacteria from the placenta invade the fetal brain
      after maternal hypoxia.

PMID- 28743957
TI  - Ubiquitin-specific protease 21 stabilizes BRCA2 to control DNA repair and tumor
      growth.
AB  - Tumor growth relies on efficient DNA repair to mitigate the detrimental impact of
      DNA damage associated with excessive cell division. Modulating repair factor
      function, thus, provides a promising strategy to manipulate malignant growth.
      Here, we identify the ubiquitin-specific protease USP21 as a positive regulator
      of BRCA2, a key mediator of DNA repair by homologous recombination. USP21
      interacts with, deubiquitinates and stabilizes BRCA2 to promote efficient RAD51
      loading at DNA double-strand breaks. As a result, depletion of USP21 decreases
      homologous recombination efficiency, causes an increase in DNA damage load and
      impairs tumor cell survival. Importantly, BRCA2 overexpression partially restores
      the USP21-associated survival defect. Moreover, we show that USP21 is
      overexpressed in hepatocellular carcinoma, where it promotes BRCA2 stability and
      inversely correlates with patient survival. Together, our findings identify
      deubiquitination as a means to regulate BRCA2 function and point to USP21 as a
      potential therapeutic target in BRCA2-proficient tumors.BRCA2 is essential for
      the repair of DNA damage; therefore, defects in BRCA2 are associated with
      tumorigenesis but also with increased susceptibility to genotoxic stress. Here
      the authors show that USP21 regulates the ability of tumor cells to repair
      damaged DNA by regulating BRCA2 stability.

PMID- 28743958
TI  - The Influence of Endogenous and Exogenous Spatial Attention on Decision
      Confidence.
AB  - Spatial attention allows us to make more accurate decisions about events in our
      environment. Decision confidence is thought to be intimately linked to the
      decision making process as confidence ratings are tightly coupled to decision
      accuracy. While both spatial attention and decision confidence have been
      subjected to extensive research, surprisingly little is known about the
      interaction between these two processes. Since attention increases performance it
      might be expected that confidence would also increase. However, two studies
      investigating the effects of endogenous attention on decision confidence found
      contradictory results. Here we investigated the effects of two distinct forms of
      spatial attention on decision confidence; endogenous attention and exogenous
      attention. We used an orientation-matching task, comparing the two attention
      conditions (endogenous and exogenous) to a control condition without directed
      attention. Participants performed better under both attention conditions than in
      the control condition. Higher confidence ratings than the control condition were
      found under endogenous attention but not under exogenous attention. This finding
      suggests that while attention can increase confidence ratings, it must be
      voluntarily deployed for this increase to take place. We discuss possible
      implications of this relative overconfidence found only during endogenous
      attention with respect to the theoretical background of decision confidence.

PMID- 28743959
TI  - Continual conscious bioluminescent imaging in freely moving somatotransgenic
      mice.
AB  - Luciferase bioimaging in living animals is increasingly being applied in many
      fields of biomedical research. Rodent imaging usually involves anaesthetising the
      animal during data capture, however, the biological consequences of anaesthesia
      have been largely overlooked. We have evaluated luciferase bioimaging in
      conscious, unrestrained mice after neonatal intracranial or intravascular
      administration of lentiviral, luciferase reporter cassettes (biosensors); we
      present real-time analyses from the first day of life to adulthood. Anaesthetics
      have been shown to exert both neurotoxic and neuroprotective effects during
      development and in models of brain injury. Mice subjected to bioimaging after
      neonatal intracranial or intravascular administration of biosensors, targeting
      the brain and liver retrospectively showed no significant difference in
      luciferase expression when conscious or unconscious throughout development. We
      applied conscious bioimaging to the assessment of NFkappaB and STAT3
      transcription factor activated reporters during the earliest stages of
      development in living, unrestrained pups. Our data showed unique longitudinal
      activities for NFkappaB and STAT3 in the brain of conscious mice. Conscious
      bioimaging was applied to a neonatal mouse model of cerebral palsy (Hypoxic
      Ischaemic Encephalopathy). Imaging of NFkappaB reporter before and after surgery
      showed a significant increase in luciferase expression, coinciding with secondary
      energy failure, in lesioned mice compared to controls.

PMID- 28743960
TI  - NADPH oxidase 4 is required for the generation of macrophage migration inhibitory
      factor and host defense against Toxoplasma gondii infection.
AB  - Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are an
      important family of catalytic enzymes that generate reactive oxygen species
      (ROS), which mediate the regulation of diverse cellular functions. Although
      phagocyte Nox2/gp91phox is closely associated with the activation of host innate
      immune responses, the roles of Nox family protein during Toxoplasma gondii (T.
      gondii) infection have not been fully investigated. Here, we found that T. gondii
      mediated ROS production was required for the upregulation of macrophage migration
      inhibitory factor (MIF) mRNA and protein levels via activation of mitogen
      activated protein kinase and nuclear factor-kappaB signaling in macrophages.
      Interestingly, MIF knockdown led to a significant increase in the survival of
      intracellular T. gondii in bone marrow-derived macrophages (BMDMs). Moreover,
      Nox4 deficiency, but not Nox2/gp91phox and the cytosolic subunit p47phox,
      resulted in enhanced survival of the intracellular T. gondii RH strain and
      impaired expression of T. gondii-mediated MIF in BMDMs. Additionally, Nox4
      deficient mice showed increased susceptibility to virulent RH strain infection
      and increased cyst burden in brain tissues and low levels of MIF expression
      following infection with the avirulent ME49 strain. Collectively, our findings
      indicate that Nox4-mediated ROS generation plays a central role in MIF production
      and resistance to T. gondii infection.

PMID- 28743961
TI  - Fragment optimization for GPCRs by molecular dynamics free energy calculations:
      Probing druggable subpockets of the A 2A adenosine receptor binding site.
AB  - Fragment-based lead discovery is becoming an increasingly popular strategy for
      drug discovery. Fragment screening identifies weakly binding compounds that
      require optimization to become high-affinity leads. As design of leads from
      fragments is challenging, reliable computational methods to guide optimization
      would be invaluable. We evaluated using molecular dynamics simulations and the
      free energy perturbation method (MD/FEP) in fragment optimization for the A2A
      adenosine receptor, a pharmaceutically relevant G protein-coupled receptor.
      Optimization of fragments exploring two binding site subpockets was probed by
      calculating relative binding affinities for 23 adenine derivatives, resulting in
      strong agreement with experimental data (R2 = 0.78). The predictive power of
      MD/FEP was significantly better than that of an empirical scoring function. We
      also demonstrated the potential of the MD/FEP to assess multiple binding modes
      and to tailor the thermodynamic profile of ligands during optimization. Finally,
      MD/FEP was applied prospectively to optimize three nonpurine fragments, and
      predictions for 12 compounds were evaluated experimentally. The direction of the
      change in binding affinity was correctly predicted in a majority of the cases,
      and agreement with experiment could be improved with rigorous parameter
      derivation. The results suggest that MD/FEP will become a powerful tool in
      structure-driven optimization of fragments to lead candidates.

PMID- 28743962
TI  - Relationship between obesity and development of erosive reflux disease: A
      mediation analysis of the role of cardiometabolic risk factors.
AB  - This study aimed to evaluate whether the relationship between obesity and erosive
      reflux disease (ERD) is mediated by cardiometabolic risk factors. This cohort
      study included subjects who underwent repeated endoscopy. To assess whether the
      association between body mass index (BMI) and ERD development was mediated by
      cardiometabolic parameters, multivariate Cox proportional hazard models were
      fitted for mediation analysis. Of 15,154 subjects with negative index endoscopy
      findings during health check-up, 11,686 subjects who underwent repeated endoscopy
      were included. During follow-up, 1,367 incident ERD events (11.7%) were observed.
      Without mediation effect, the multivariate adjusted hazard ratio of BMI was 1.21
      (95% CI, 1.03-1.42) in overweight and 1.39 (95% CI, 1.19-1.62) in obese
      individuals compared to normal weight individuals. When the metabolic syndrome
      was included as a mediator, the hazard ratio became 1.19 (95% CI, 1.00-1.40) in
      overweight and 1.29 (95% CI, 1.10-1.52) in obese individuals. Both systolic blood
      pressure and triglyceride level were found to fully mediate the effect of BMI on
      ERD. Fasting glucose level was a partial mediator. The estimated percentage of
      total effect mediated by cardiometabolic risk factors was 35.4%. Cardiometabolic
      parameters partially or fully mediate the association between overweight and
      obesity and incident ERD.

PMID- 28743963
TI  - A non-canonical pathway regulates ER stress signaling and blocks ER stress
      induced apoptosis and heart failure.
AB  - Endoplasmic reticulum stress is an evolutionarily conserved cell stress response
      associated with numerous diseases, including cardiac hypertrophy and heart
      failure. The major endoplasmic reticulum stress signaling pathway causing cardiac
      hypertrophy involves endoplasmic reticulum stress sensor PERK (protein kinase
      like kinase) and eIF2alpha-ATF4-CHOP signaling. Here, we describe a non
      canonical, AGGF1-mediated regulatory system for endoplasmic reticulum stress
      signaling associated with increased p-eIF2alpha and ATF4 and decreased sXBP1 and
      CHOP. Specifically, we see a reduced AGGF1 level consistently associated with
      induction of endoplasmic reticulum stress signaling in mouse models and human
      patients with heart failure. Mechanistically, AGGF1 regulates endoplasmic
      reticulum stress signaling by inhibiting ERK1/2 activation, which reduces the
      level of transcriptional repressor ZEB1, leading to induced expression of miR-183
      5p. miR-183-5p post-transcriptionally downregulates CHOP and inhibits endoplasmic
      reticulum stress-induced apoptosis. AGGF1 protein therapy and miR-183-5p regulate
      endoplasmic reticulum stress signaling and block endoplasmic reticulum stress
      induced apoptosis, cardiac hypertrophy, and heart failure, providing an
      attractive paradigm for treatment of cardiac hypertrophy and heart
      failure.Endoplasmic reticulum (ER) stress promotes cardiac dysfunction. Here the
      authors uncover a pathway whereby AGGF1 blocks ER stress by inhibiting ERK1/2
      activation and the transcriptional repressor ZEB1, leading to induction of miR
      183-5p and down-regulation of CHOP, and show that AGGF1 can effectively treat
      cardiac hypertrophy and heart failure.

PMID- 28743964
TI  - Toll-like Receptor 4 Deficiency Reduces Oxidative Stress and Macrophage Mediated
      Inflammation in Hypertensive Kidney.
AB  - Oxidative stress and inflammation are integral to hypertension-induced renal
      injury. A unifying feature for the two components is Toll-like receptors (TLR),
      which are key regulators of the innate immune system. Recent studies implicate
      TLR4 activation and oxidative stress in cardiovascular diseases and also as a
      link between inflammation and hypertension. However, its role in hypertension
      induced renal injury remains unexplored. In the present study, we investigated
      whether TLR-4 deficiency reduces Ang-II-induced renal injury and fibrosis by
      attenuating reactive oxygen species (ROS) production and inflammation. C3H/HeOuJ
      mice with normal TLR-4 and C3H/HeJ Lps-d with dysfunctional TLR4 (TLR4
      deficiency) were treated without or with Ang-II. In response to Ang-II, TLR4
      deficient mice had reduced renal resistive index and increased renal cortical
      blood flow compared to mice with normal TLR4. Further, TLR4 deficiency reduced
      oxidative stress and increased antioxidant capacity (MnSOD, CuSOD and Catalase
      activity). TLR4 deficiency was also associated with reduced inflammation (MCP-1,
      MIP-2, TNF-alpha, IL-6 and CD68), decreased accumulation of bone marrow-derived
      fibroblasts and TGF-beta expression. Our data suggests that in C3H/HeJ Lps-d
      mice, deficiency of functional TLR4 reduces oxidative stress and macrophage
      activation to decrease TGF-beta-induced extracellular matrix protein deposition
      in the kidney in Ang-II induced hypertension.

PMID- 28743965
TI  - Nanocrystalline diamond protects Zr cladding surface against oxygen and hydrogen
      uptake: Nuclear fuel durability enhancement.
AB  - In this work, we demonstrate and describe an effective method of protecting
      zirconium fuel cladding against oxygen and hydrogen uptake at both accident and
      working temperatures in water-cooled nuclear reactor environments. Zr alloy
      samples were coated with nanocrystalline diamond (NCD) layers of different
      thicknesses, grown in a microwave plasma chemical vapor deposition apparatus. In
      addition to showing that such an NCD layer prevents the Zr alloy from directly
      interacting with water, we show that carbon released from the NCD film enters the
      underlying Zr material and changes its properties, such that uptake of oxygen and
      hydrogen is significantly decreased. After 100-170 days of exposure to hot water
      at 360  degrees C, the oxidation of the NCD-coated Zr plates was typically
      decreased by 40%. Protective NCD layers may prolong the lifetime of nuclear
      cladding and consequently enhance nuclear fuel burnup. NCD may also serve as a
      passive element for nuclear safety. NCD-coated ZIRLO claddings have been selected
      as a candidate for Accident Tolerant Fuel in commercially operated reactors in
      2020.

PMID- 28743966
TI  - Pupil adaptation corresponds to quantitative measures of autism traits in
      children.
AB  - The pupil is known to reflect a range of psychological and physiological
      variables, including cognitive effort, arousal, attention, and even learning.
      Within autism spectrum disorder (ASD), some work has used pupil physiology to
      successfully classify patients with or without autism. As we have come to
      understand the heterogeneity of ASD and other neurodevelopmental disorders, the
      relationship between quantitative traits and physiological markers has become
      increasingly more important, as this may lead us closer to the underlying
      biological basis for atypical responses and behaviors. We implemented a novel
      paradigm designed to capture patterns of pupil adaptation during sustained
      periods of dark and light conditions in a pediatric sample that varied in
      intellectual ability and clinical features. We also investigate the relationship
      between pupil metrics derived from this novel task and quantitative behavioral
      traits associated with the autism phenotype. We show that pupil metrics of
      constriction and dilation are distinct from baseline metrics. Pupil dilation
      metrics correlate with individual differences measured by the Social
      Responsiveness Scale (SRS), a quantitative measure of autism traits. These
      results suggest that using a novel, yet simple, paradigm can result in meaningful
      pupil metrics that correlate with individual differences in autism traits, as
      measured by the SRS.

PMID- 28743967
TI  - Pathogen recognition in compatible plant-microbe interactions.
AB  - Microbial infections in plant leaves remain a major challenge in agriculture.
      Hence an understanding of disease mechanisms at the molecular level is of
      paramount importance for identifying possible intervention points for their
      control. Whole-transcriptome changes during early disease stages in susceptible
      plant species are less well-documented than those of resistant ones. This study
      focuses on the differential transcriptional changes at 24 hours post inoculation
      (hpi) in tomato leaflets affected by three pathogens: (1) Phytophthora infestans,
      (2) Botrytis cinerea, and (3) Oidium neolycopersici. Grey mould (B. cinerea) was
      the disease that had progressed the most by 24 hpi, both in terms of visible
      symptoms as well as differential gene expression. By means of RNA-seq, we
      identified 50 differentially expressed tomato genes specifically induced by B.
      cinerea infection and 18 specifically induced by P. infestans infection at 24
      hpi. Additionally, a set of 63 genes were differentially expressed during all
      three diseases when compared by a Bayesian approach to their respective mock
      infections. And Gene expression patterns were found to also depend on the
      inoculation technique. These findings suggest a specific and distinct
      transcriptional response in plant leaf tissue in reaction to B. cinerea and P.
      infestans invasion at 24 hpi, indicating that plants may recognize the attacking
      pathogen.

PMID- 28743968
TI  - Impact of isovalent and aliovalent substitution on the mechanical and thermal
      properties of Gd2Zr2O7.
AB  - In this study, a density functional theory method is employed to investigate the
      effects of isovalent and aliovalent substitution of Sm3+ on the phase stability,
      thermo-physical properties and electronic structure of Gd2Zr2O7. It is shown that
      the isovalent substitution of Sm3+ for Gd3+ results in the formation of Gd2Zr2O7
      Sm2Zr2O7 solid solution, which retains the pyrochlore structure and has slight
      effects on the elastic moduli, ductility, Debye temperature and band gap of
      Gd2Zr2O7. As for the aliovalent substitution of Sm3+ for Zr4+ site, a pyrochlore
      to-defect fluorite structural transition is induced, and the mechanical, thermal
      properties and electronic structures are influenced significantly. As compared
      with the Gd2Zr2O7, the resulted Gd2SmyZr2-yO7 compositions have much smaller
      elastic moduli, better ductility and smaller Debye temperature. Especially, an
      amount of electrons distribute on the fermi level and they are expected to have
      larger thermal conductivity than Gd2Zr2O7. This study suggests an alternative way
      to engineer the thermo-physical properties of Gd2Zr2O7 and will be beneficial for
      its applications under stress and high temperature.

PMID- 28743969
TI  - Human amniotic membrane as newly identified source of amniotic fluid pulmonary
      surfactant.
AB  - Pulmonary surfactant (PS) reduces surface tension at the air-liquid interface in
      the alveolar epithelium of the lung, which is required for breathing and for the
      pulmonary maturity of the developing foetus. However, the origin of PS had never
      been thoroughly investigated, although it was assumed to be secreted from the
      foetal developing lung. Human amniotic membrane (hAM), particularly its
      epithelial cell layer, composes the amniotic sac enclosing the amniotic fluid. In
      this study, we therefore aimed to investigate a potential contribution of the
      cellular components of the hAM to pulmonary surfactant found in amniotic fluid.
      We identified that cells within the native membrane contain lamellar bodies and
      express all four surfactant proteins as well as ABCA3. Lipidomic profiling by
      nanoESI - MS/MS revealed the presence of the essential lipid species as found in
      PS. Also, the biophysical activity of conditioned cell culture supernatant
      obtained from hAM was tested with captive bubble surfactometry. hAM supernatant
      showed the ability to reduce surface tension, similar to human PS obtained from
      bronchoalveolar lavage. This means that hAM produces the essential PS-associated
      components and can therefore contribute as second potential source of PS in
      amniotic fluid aside from the foetal lung.

PMID- 28743970
TI  - ADME-Space: a new tool for medicinal chemists to explore ADME properties.
AB  - We introduce a new chemical space for drugs and drug-like molecules, exclusively
      based on their in silico ADME behaviour. This ADME-Space is based on self
      organizing map (SOM) applied to 26,000 molecules. Twenty accurate QSPR models,
      describing important ADME properties, were developed and, successively, used as
      new molecular descriptors not related to molecular structure. Applications
      include permeability, active transport, metabolism and bioavailability studies,
      but the method can be even used to discuss drug-drug interactions (DDIs) or it
      can be extended to additional ADME properties. Thus, the ADME-Space opens a new
      framework for the multi-parametric data analysis in drug discovery where all ADME
      behaviours of molecules are condensed in one map: it allows medicinal chemists to
      simultaneously monitor several ADME properties, to rapidly select optimal ADME
      profiles, retrieve warning on potential ADME problems and DDIs or select proper
      in vitro experiments.

PMID- 28743971
TI  - Muscle transcriptome analysis reveals molecular pathways and biomarkers involved
      in extreme ultimate pH and meat defect occurrence in chicken.
AB  - The processing ability and sensory quality of chicken breast meat are highly
      related to its ultimate pH (pHu), which is mainly determined by the amount of
      glycogen in the muscle at death. To unravel the molecular mechanisms underlying
      glycogen and meat pHu variations and to identify predictive biomarkers of these
      traits, a transcriptome profiling analysis was performed using an Agilent custom
      chicken 8 * 60 K microarray. The breast muscle gene expression patterns were
      studied in two chicken lines experimentally selected for high (pHu+) and low (pHu
      ) pHu values of the breast meat. Across the 1,436 differentially expressed (DE)
      genes found between the two lines, many were involved in biological processes
      related to muscle development and remodelling and carbohydrate and energy
      metabolism. The functional analysis showed an intensive use of carbohydrate
      metabolism to produce energy in the pHu- line, while alternative catabolic
      pathways were solicited in the muscle of the pHu+ broilers, compromising their
      muscle development and integrity. After a validation step on a population of 278
      broilers using microfluidic RT-qPCR, 20 genes were identified by partial least
      squares regression as good predictors of the pHu, opening new perspectives of
      screening broilers likely to present meat quality defects.

PMID- 28743972
TI  - The power of a control qubit in weak measurements.
AB  - In the late 80 s, a curious effect suggested by Aharanov et al. was found to lead
      to an anomalous amplification based on quantum measurements of weakly coupled
      systems. In this paper, we investigate the quantum control of the weak value
      amplification of a qubit system coupled to a meter. For the qubit system, the
      coupling occurs via a second non-interacting qubit, initially quantum correlated
      with the first one. We show that for weak measurements, the control can be
      remotely realized via the post-selected state of the second qubit or the degree
      of squeezing of the meter. In our study of the quantum control of the
      amplification, we can easily manipulate the degree of quantum correlations
      between the initially correlated qubits. We find that the degree of entanglement
      has no effect on the quantum control of the amplification. However, we also found
      a clear connection between the amplification and quantum discord like
      measurements as well as classical correlations between the qubits. Finally, we
      suggest an application of the amplification control on the enhancement of the
      quantum measurement accuracy, e.g. measuring the relative phase of the post
      selected control qubit in a more precise way, as opposed to the non-amplified
      case.

PMID- 28743973
TI  - In vivo efficacy of beta-lactam/tripropeptin C in a mouse septicemia model and
      the mechanism of reverse beta-lactam resistance in methicillin-resistant
      Staphylococcus aureus mediated by tripropeptin C.
AB  - Natural lipopeptide antibiotic tripropeptin C (TPPC) revitalizes and
      synergistically potentiates the activities of the class of beta-lactam
      antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) but not
      against methicillin-sensitive S. aureus in vitro; however, the mode of action
      remains unclear. In the course of the study to reveal its mode of action, we
      found that TPPC inhibited the beta-lactamase production induced by cefotiam. This
      prompted us to focus on the beta-lactam-inducible beta-lactam-resistant genes
      blaZ (beta-lactamase) and mecA (foreign penicillin-binding protein), as they are
      mutually regulated by the blaZ/I/R1 and mecA/I/R1 systems. Quantitative reverse
      transcription polymerase chain reaction analysis revealed that TPPC reversed beta
      lactam resistance by reducing the expression of the genes blaZ and mecA, when
      treated alone or in combination with beta-lactam antibiotics. In a mouse/MRSA
      septicemia model, subcutaneous injection of a combination of TPPC and ceftizoxime
      demonstrated synergistic therapeutic efficacy compared with each drug alone.
      These observations strongly suggested that reverse beta-lactam resistance by TPPC
      may be a potentially effective new therapeutic strategy to overcome refractory
      MRSA infections.The Journal of Antibiotics advance online publication, 26 July
      2017; doi:10.1038/ja.2017.88.

PMID- 28743974
TI  - Heterocyclyl tetracyclines. 2. 7-Methoxy-8-pyrrolidinyltetracyclines: discovery
      of TP-2758, a potent, orally efficacious antimicrobial against Gram-negative
      pathogens.
AB  - A convergent total synthesis platform led to the discovery of TP-2758 from a
      series of novel 7-methoxy-8-heterocyclyl tetracycline analogs. TP-2758
      demonstrated high in vitro potency against key Gram-negative pathogens including
      extended spectrum beta-lactamases- and carbapenemase-producing Enterobacteriaceae
      and Acinetobacter spp. strains. This compound was efficacious when administered
      either intravenously or orally in multiple murine infection models and displayed
      a favorable preclinical pharmacological profile supporting its advancement into
      clinical development.

PMID- 28743975
TI  - Synthesis of unique spirocyclic orthoester-type derivatives of isothiazolo[4,3
      d]pyrimidine nucleosides.
AB  - A set of unique nucleoside analogs, containing 'spirocyclic orthoester-type'
      scaffolds, were synthesized from a common isothiazolo[4,3-d]pyrimidine-riboside
      precursor. The key reaction, using 1,2-di-heteroatomic nucleophiles (e.g., 1,2
      ethandithiol) and BF3*OEt2, converts an exocyclic imine into the spirocyclic
      analogs. The novel structural scaffold is confirmed through the use of one- and
      two-dimensional 1H and 13C NMR experiments.

PMID- 28743976
TI  - Nano-plasmonic near field phase matching of attosecond pulses.
AB  - Nano-structures excited by light can enhance locally the electric field when
      tuned to plasmonic resonances. This phenomenon can be used to boost non-linear
      processes such as harmonic generation in crystals or in gases, Raman excitation,
      and four wave mixing. Here we present a theoretical investigation of the near
      field phase matching of attosecond pulses emitted by high-order harmonic
      generation (HHG) of an atom immersed in a multi-cycle femtosecond infrared laser
      field and a spatially inhomogeneous plasmonic field. We demonstrate that the
      spatial inhomogeneity factor of the plasmonic field strongly affects the electron
      trajectory and recombination time which can be used to control the attosecond
      emission. For further insight into the plasmonic field effect, we monitor the
      phase of each quantum path as a function of the inhomogeneity strength. Moreover,
      we investigate the attosecond emission as a function of near-field phase matching
      effects. This is achieved by calculating the coherent field superposition of
      attosecond pulses emitted from various intensities or field inhomogeneities.
      Finally, far-field and near-field phase matching effects are combined to modulate
      the harmonic spectral phase towards the emission of a single attosecond pulse.

PMID- 28743977
TI  - The association of serum adiponectin with abdominal aortic calcification in
      Japanese male hemodialysis patients: a cross-sectional observational study.
AB  - The negative relation of serum adiponectin to atherosclerosis becomes a positive
      association in patients with chronic kidney disease (CKD). We conducted a small
      scale cross-sectional observational study, in 101 Japanese male hemodialysis
      patients, to examine the relationship of serum adiponectin and leptin to
      abdominal aortic calcification (AAC). The presence of AAC was evaluated from
      simple X-ray radiographs of the left lateral abdomen. Serum adiponectin was
      significantly higher in AAC-positive patients [18.8 (13.0-28.1) MUg/mL] than in
      AAC-negative patients [15.4 (8.9-22.8) MUg/mL] (p = 0.03), whereas serum leptin
      did not differ significantly between the two groups. Multiple logistic regression
      analysis showed that log adiponectin, but not log leptin, was independently and
      significantly associated in a positive manner with AAC (odds ratio: 16.31, 95%
      confidence interval: 1.70-156.41, p = 0.02), after adjustment for age, body
      weight, percentage body fat, hemodialysis duration, prevalence of diabetes
      mellitus, and other risk factors. In conclusion, we found a positive and
      independent association of serum adiponectin with AAC in male hemodialysis
      patients, indicating that the reversed association between serum adiponectin and
      atherosclerosis in patients with CKD dose not result from increased serum
      adiponectin due to the impaired urinary secretion.

PMID- 28743978
TI  - Collaborative roles of Temporoparietal Junction and Dorsolateral Prefrontal
      Cortex in Different Types of Behavioural Flexibility.
AB  - Behavioural flexibility is essential for everyday life. This involves shifting
      attention between different perspectives. Previous studies suggest that
      flexibility is mainly subserved by the dorsolateral prefrontal cortex (DLPFC).
      However, although rarely emphasized, the temporoparietal junction (TPJ) is
      frequently recruited during flexible behaviour. A crucial question is whether TPJ
      plays a role in different types of flexibility, compared to its limited role in
      perceptual flexibility. We hypothesized that TPJ activity during diverse
      flexibility tasks plays a common role in stimulus-driven attention-shifting,
      thereby contributing to different types of flexibility, and thus the
      collaboration between DLPFC and TPJ might serve as a more appropriate mechanism
      than DLPFC alone. We used fMRI to measure DLPFC/TPJ activity recruited during
      moral flexibility, and examined its effect on other domains of flexibility
      (economic/perceptual). Here, we show the additional, yet crucial role of TPJ: a
      combined DLPFC/TPJ activity predicted flexibility, regardless of domain.
      Different types of flexibility might rely on more basic attention-shifting, which
      highlights the behavioural significance of alternatives.

PMID- 28743979
TI  - Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines
      chondrogenic differentiation.
AB  - Mutations in the RMRP-gene, encoding the lncRNA component of the RNase MRP
      complex, are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia
      is associated with severe dwarfism caused by impaired skeletal development.
      However, it is not clear why mutations in RMRP RNA lead to skeletal dysplasia.
      Since chondrogenic differentiation of the growth plate is required for
      development of long bones, we hypothesized that RMRP RNA plays a pivotal role in
      chondrogenic differentiation. Expression of Rmrp RNA and RNase MRP protein
      subunits was detected in the murine growth plate and during the course of
      chondrogenic differentiation of ATDC5 cultures, where Rmrp RNA expression was
      found to be correlated with chondrocyte hypertrophy. Genetic interference with
      Rmrp RNA expression in ATDC5 cultures caused a deregulation of chondrogenic
      differentiation, with a prominent impact on hypertrophy and changes in pre-rRNA
      processing and rRNA levels. Promoter reporter studies showed that Rmrp RNA
      expression responds to chondrogenic morphogens. Chondrogenic trans
      differentiation of cartilage-hair hypoplasia fibroblasts was impaired with a
      pronounced impact on hypertrophic differentiation. Together, our data show that
      RMRP RNA expression is regulated during different stages of chondrogenic
      differentiation and indicate that RMRP RNA may play a pivotal role in chondrocyte
      hypertrophy, with potential consequences for CHH pathobiology.

PMID- 28743981
TI  - NAFLD: Type 2 immunity drives progression of NAFLD.

PMID- 28743980
TI  - Chelant Enhanced Solution Processing for Wafer Scale Synthesis of Transition
      Metal Dichalcogenide Thin Films.
AB  - It is of paramount importance to improve the control over large area growth of
      high quality molybdenum disulfide (MoS2) and other types of 2D dichalcogenides.
      Such atomically thin materials have great potential for use in electronics, and
      are thought to make possible the first real applications of spintronics. Here in,
      a facile and reproducible method of producing wafer scale atomically thin MoS2
      layers has been developed using the incorporation of a chelating agent in a
      common organic solvent, dimethyl sulfoxide (DMSO). Previously, solution
      processing of a MoS2 precursor, ammonium tetrathiomolybdate ((NH4)2MoS4), and
      subsequent thermolysis was used to produce large area MoS2 layers. Our work here
      shows that the use of ethylenediaminetetraacetic acid (EDTA) in DMSO exerts
      superior control over wafer coverage and film thickness, and the results
      demonstrate that the chelating action and dispersing effect of EDTA is critical
      in growing uniform films. Raman spectroscopy, photoluminescence (PL), x-ray
      photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR),
      atomic force microscopy (AFM) and high-resolution scanning transmission electron
      microscopy (HR-STEM) indicate the formation of homogenous few layer MoS2 films at
      the wafer scale, resulting from the novel chelant-in-solution method.

PMID- 28743982
TI  - Oesophageal cancer: RNA editing of SLC22A3 mRNAs: causative relevance to familial
      ESCC?

PMID- 28743983
TI  - Liver: Cholangiocytes regenerate hepatocytes during severe liver injury.

PMID- 28743984
TI  - Gut microbiota and IBD: causation or correlation?
AB  - A general consensus exists that IBD is associated with compositional and
      metabolic changes in the intestinal microbiota (dysbiosis). However, a direct
      causal relationship between dysbiosis and IBD has not been definitively
      established in humans. Findings from animal models have revealed diverse and
      context-specific roles of the gut microbiota in health and disease, ranging from
      protective to pro-inflammatory actions. Moreover, evidence from these
      experimental models suggest that although gut bacteria often drive immune
      activation, chronic inflammation in turn shapes the gut microbiota and
      contributes to dysbiosis. The purpose of this Review is to summarize current
      associations between IBD and dysbiosis, describe the role of the gut microbiota
      in the context of specific animal models of colitis, and discuss the potential
      role of microbiota-focused interventions in the treatment of human IBD.
      Ultimately, more studies will be needed to define host-microbial relationships
      relevant to human disease and amenable to therapeutic interventions.

PMID- 28743985
TI  - Loss of ERalpha partially reverses the effects of maternal high-fat diet on
      energy homeostasis in female mice.
AB  - Maternal high-fat diet (HFD) alters hypothalamic developmental programming and
      disrupts offspring energy homeostasis in rodents. 17beta-estradiol (E2) also
      influences hypothalamic programming through estrogen receptor (ER) alpha.
      Therefore, we hypothesized that females lacking ERalpha would be more susceptible
      to maternal HFD. To address this question, heterozygous ERalpha knockout (WT/KO)
      dams were fed a control breeder chow diet (25% fat) or a semi-purified HFD (45%
      fat) 4 weeks prior to mating with WT/KO males or heterozygous males with an
      ERalpha DNA-binding domain mutation knocked in (WT/KI) to produce WT, ERalpha KO,
      or ERalpha KIKO females lacking ERE-dependent ERalpha signaling. Maternal HFD
      increased body weight in WT and KIKO, in part, due to increased adiposity and
      daytime carbohydrate utilization in WT and KIKO, while increasing nighttime fat
      utilization in KO. Maternal HFD also increased plasma leptin, IL-6, and MCP-1 in
      WT and increased arcuate expression of Kiss1 and Esr1 (ERalpha) and liver
      expression of G6pc and Pepck in WT and KIKO. Contrary to our hypothesis, these
      data suggest that loss of ERalpha signaling blocks the influence of maternal HFD
      on energy homeostasis, inflammation, and hypothalamic and liver gene expression
      and that restoration of ERE-independent ERalpha signaling partially reestablishes
      susceptibility to maternal HFD.

PMID- 28743986
TI  - An extended PROSPECT: Advance in the leaf optical properties model separating
      total chlorophylls into chlorophyll a and b.
AB  - The PROSPECT leaf optical model has, to date, well-separated the effects of total
      chlorophyll and carotenoids on leaf reflectance and transmittance in the 400-800
      nm. Considering variations in chlorophyll a:b ratio with leaf age and
      physiological stress, a further separation of total plant-based chlorophylls into
      chlorophyll a and chlorophyll b is necessary for advanced monitoring of plant
      growth. In this study, we present an extended version of PROSPECT model
      (hereafter referred to as PROSPECT-MP) that can combine the effects of
      chlorophyll a, chlorophyll b and carotenoids on leaf directional hemispherical
      reflectance and transmittance (DHR and DHT) in the 400-800 nm. The LOPEX93
      dataset was used to evaluate the capabilities of PROSPECT-MP for spectra
      modelling and pigment retrieval. The results show that PROSPECT-MP can both
      simultaneously retrieve leaf chlorophyll a and b, and also performs better than
      PROSPECT-5 in retrieving carotenoids concentrations. As for the simulation of DHR
      and DHT, the performances of PROSPECT-MP are similar to that of PROSPECT-5. This
      study demonstrates the potential of PROSPECT-MP for improving capabilities of
      remote sensing of leaf photosynthetic pigments (chlorophyll a, chlorophyll b and
      carotenoids) and for providing a framework for future refinements in the
      modelling of leaf optical properties.

PMID- 28743987
TI  - Empathy for others' suffering and its mediators in mental health professionals.
AB  - Empathy is a complex cognitive and affective process that allows humans to
      experience concern for others, comprehend their emotions, and eventually help
      them. In addition to studies with healthy subjects and various neuropsychiatric
      populations, a few reports have examined this domain focusing on mental health
      workers, whose daily work requires the development of a saliently empathic
      character. Building on this research line, the present population-based study
      aimed to (a) assess different dimensions of empathy for pain in mental health
      workers relative to general-physicians and non-medical workers; and (b) evaluate
      their relationship with relevant factors, such as moral profile, age, gender,
      years of experience, and workplace type. Relative to both control groups, mental
      health workers exhibited higher empathic concern and discomfort for others'
      suffering, and they favored harsher punishment to harmful actions. Furthermore,
      this was the only group in which empathy variability was explained by moral
      judgments, years of experience, and workplace type. Taken together, these results
      indicate that empathy is continuously at stake in mental health care scenarios,
      as it can be affected by contextual factors and social contingencies. More
      generally, they highlight the importance of studying this domain in populations
      characterized by extreme empathic demands.

PMID- 28743988
TI  - Strain Balanced AlGaN/GaN/AlGaN nanomembrane HEMTs.
AB  - Single crystal semiconductor nanomembranes (NM) are important in various
      applications such as heterogeneous integration and flexible devices. This paper
      reports the fabrication of AlGaN/GaN NMs and NM high electron mobility
      transistors (HEMT). Electrochemical etching is used to slice off single
      crystalline AlGaN/GaN layers while preserving their microstructural quality. A
      double heterostructure design with a symmetric strain profile is employed to
      ensure minimal residual strain in freestanding NMs after release. The mobility of
      the two-dimensional electron gas (2DEG), formed by the AlGaN/GaN heterostructure,
      is noticeably superior to previously reported values of many other NMs. AlGaN/GaN
      nanomembrane HEMTs are fabricated on SiO2 and flexible polymeric substrates.
      Excellent electrical characteristics, including a high ON/OFF ratio and
      transconductance, suggest that III-Nitrides nanomembranes are capable of
      supporting high performance applications.

PMID- 28743989
TI  - Apoptosis inhibitor of macrophage ameliorates fungus-induced peritoneal injury
      model in mice.
AB  - Fungal peritonitis in a patient on peritoneal dialysis (PD) is a refractory
      injury accompanied by severe inflammation, predisposing patients to a poor
      prognosis. Defective clearance of necrotic tissue interferes with amelioration of
      tissue injury and induces abnormal tissue remodeling. In the recent reports,
      apoptosis inhibitor of macrophage (AIM, also called CD5L) prevents obesity,
      hepatocellular carcinoma and acute kidney injury. Here, we investigated potential
      roles of AIM in prevention of progression of fungal peritonitis models. AIM -/-
      mice subjected to zymosan-induced peritonitis exhibited progressive inflammation
      and sustained peritoneal necrosis tissue on day 28 after the disease induction,
      whereas there was an improvement in AIM +/+ mice. This appeared to be caused by
      deposition of AIM at the necrotic peritoneum in AIM +/+ mice. In vitro, AIM
      enhanced the engulfment of necrotic debris by macrophages derived from zymosan
      induced peritonitis, M1- and M2a-like bone marrow derived macrophages, as well as
      by mesothelial cells. In addition, administration of recombinant AIM dramatically
      ameliorated severe inflammation associated with necrosis in zymosan-induced
      peritonitis of AIM -/- mice. Our observations suggest that AIM appears to be
      involved in the repair process of zymosan-induced peritonitis, and thus, could be
      the basis of development of new therapeutic strategies for PD-related fungal
      peritonitis.

PMID- 28743990
TI  - Formulating formation mechanism of natural gas hydrates.
AB  - A large amount of energy, perhaps twice the total amount of all other hydrocarbon
      reserves combined, is trapped within gas hydrate deposits. Despite emerging as a
      potential energy source for the world over the next several hundred years and one
      of the key factors in causing future climate change, gas hydrate is poorly known
      in terms of its formation mechanism. To address this issue, a mathematical
      formulation is proposed in the form of a model to represent the physical insight
      into the process of hydrate growth that occurs on the surface and in the
      irregular nanometer-sized pores of the distributed porous particles. To evaluate
      the versatility of this rigorous model, the experimental data is used for methane
      (CH4) and carbon dioxide (CO2) hydrates grown in different porous media with a
      wide range of considerations.

PMID- 28743991
TI  - Altered visual cortical processing in a mouse model of MECP2 duplication
      syndrome.
AB  - As an epigenetic modulator of gene expression, Methyl-CpG binding protein 2
      (MeCP2) is essential for normal neurological function. Dysfunction of MeCP2 is
      associated with a variety of neurological disorders. MECP2 gene duplication in
      human causes neuropsychiatric symptoms such as mental retardation and autism.
      MeCP2 overexpression in mice results in neurobehavioural disorders, dendritic
      abnormalities, and synaptic defects. However, how gain of MeCP2 function
      influences cortical processing of sensory information remains unclear. In this
      study, we examined visual processing in a mouse model of MECP2 duplication
      syndrome (MECP2 Tg1 mouse) at 8 and 14 weeks, which were before and after the
      onset of behavioural symptoms, respectively. In vivo extracellular recordings
      from primary visual cortex (V1) showed that neurons in Tg1 mice at both adult
      ages preferred higher spatial frequencies (SFs) than those in wild-type (WT)
      littermate controls, and the semi-saturation contrasts of neurons were lower in
      Tg1 mice at 8 weeks but not at 14 weeks. Behavioural experiments showed that the
      performance for visual detection at high SFs and low contrasts was higher in
      MECP2 Tg1 mice. Thus, MeCP2 gain-of-function in mice leads to higher visual
      acuity and contrast sensitivity, both at the levels of cortical response and
      behavioural performance.

PMID- 28743992
TI  - Endotoxemia-mediated activation of acetyltransferase P300 impairs insulin
      signaling in obesity.
AB  - Diabetes and obesity are characterized by insulin resistance and chronic low
      grade inflammation. An elevated plasma concentration of lipopolysaccharide (LPS)
      caused by increased intestinal permeability during diet-induced obesity promotes
      insulin resistance in mice. Here, we show that LPS induces endoplasmic reticulum
      (ER) stress and protein levels of P300, an acetyltransferase involved in glucose
      production. In high-fat diet fed and genetically obese ob/ob mice, P300
      translocates from the nucleus into the cytoplasm of hepatocytes. We also
      demonstrate that LPS activates the transcription factor XBP1 via the ER stress
      sensor IRE1, resulting in the induction of P300 which, in turn, acetylates
      IRS1/2, inhibits its association with the insulin receptor, and disrupts insulin
      signaling. Pharmacological inhibition of P300 acetyltransferase activity by a
      specific inhibitor improves insulin sensitivity and decreases hyperglycemia in
      obese mice. We suggest that P300 acetyltransferase activity may be a promising
      therapeutic target for the treatment of obese patients.Elevated plasma LPS levels
      have been associated with insulin resistance. Here Cao et al. show that LPS
      induces ER stress and P300 activity via the XBP1/IRE1 pathway. P300 acetylates
      IRS1/2 and inhibits its binding with the insulin receptor. The consequent
      impairment of insulin signaling can be rescued by pharmacological inhibition of
      P300.

PMID- 28743993
TI  - YY1's role in the Peg3 imprinted domain.
AB  - The ICR (Imprinting Control Region) of the Peg3 (Paternally Expressed Gene 3)
      domain contains an unusual cluster of YY1 binding sites. In the current study,
      these YY1 binding sites were mutated to characterize the unknown roles in the
      mouse Peg3 domain. According to the results, paternal and maternal transmission
      of the mutant allele did not cause any major effect on the survival of the pups.
      In the mutants, the maternal-specific DNA methylation on the ICR was properly
      established and maintained, causing no major effect on the imprinting of the
      domain. In contrast, the paternal transmission resulted in changes in the
      expression levels of several genes: down-regulation of Peg3 and Usp29 and up
      regulation of Zim1. These changes were more pronounced during the neonatal stage
      than during the adult stage. In the case of Peg3 and Zim1, the levels of the
      observed changes were also different between males and females, suggesting the
      different degrees of YY1 involvement between two sexes. Overall, the results
      indicated that YY1 is mainly involved in controlling the transcriptional levels,
      but not the DNA methylation, of the Peg3 domain.

PMID- 28743994
TI  - Autistic traits and positive psychotic experiences modulate the association of
      psychopathic tendencies with theory of mind in opposite directions.
AB  - Various clinical disorders, including psychopathy, and autism and schizophrenia
      spectrum disorders, have been linked with impairments in Theory of Mind (ToM).
      However, although these conditions can co-occur in the same individual, the
      effect of their inter-play on ToM abilities has not been investigated. Here we
      assessed ToM abilities in 55 healthy adults while performing a naturalistic ToM
      task, requiring participants to watch a short film and judge the actors' mental
      states. The results reveal for the first time that autistic traits and positive
      psychotic experiences interact with psychopathic tendencies in opposite
      directions to predict ToM performance-the interaction of psychopathic tendencies
      with autism traits was associated with a decrement in performance, whereas the
      interaction of psychopathic tendencies and positive psychotic experiences was
      associated with improved performance. These effects were specific to cognitive
      rather than affective ToM. These results underscore the importance of the
      simultaneous assessment of these dimensions within clinical settings. Future
      research in these clinical populations may benefit by taking into account such
      individual differences.

PMID- 28743995
TI  - Non-invasive 3D and 360 degrees  optical imaging of micro-particles.
AB  - Scanning electron microscopy and X-ray microtomography are useful methods for
      high resolution shape imaging. Visible microscopy is also common, however,
      developing a low-cost and customizable system for surface and shape investigation
      of optically active particles is challenging. In this work, we demonstrate an
      assembly offering good light sensitivity, flexibility of illumination and
      contrasts from varying angles. The design was applied, together with recent
      programs for focus-stacking, to analyze crystals of taurine, L-glutamic acid,
      acetylsalicylic acid, and copper sulfate, along with digital 3D-360 degrees 
      modelling of phosphorescent [Ru(bpy)3]Cl2 and strontium aluminate particles. We
      further tested the approach for real time monitoring of size, shape and texture
      analysis of fat filled milk particles and acid whey powders. The findings show
      proof of concept for detailed feature imaging of particles directly from the
      process environment.

PMID- 28743996
TI  - Antecedent soil moisture prior to freezing can affect quantity, composition and
      stability of soil dissolved organic matter during thaw.
AB  - There are large amounts of dissolved organic matter (DOM) released into the soil
      during spring thaw, but its bioavailability and components are still unknown. The
      quantity, composition and stability of DOM in water extracts of forest soils
      during thaw were studied after two-month freezing with 9 levels of soil moisture
      ranging from 10% to 90% water-filled pore space (WFPS), by measuring soil carbon
      dioxide (CO2) flux, biodegradable dissolved organic carbon (BDOC) and nitrogen
      (BDON), ultraviolet absorbance and parallel factor analysis of fluorescence
      excitation-emission matrices. Concentrations of BDOC, BDON, DOC and DON were
      lowest around 30% WFPS and relatively higher and lower soil moisture both
      increased DOM and BDOM concentrations in thawing soil. With increasing WFPS, the
      dominant component of soil DOM changed from humic acid-like substances to fulvic
      acid-like substances and the biological origin of DOM increased gradually. The
      protein-like component accounted for 8-20% of soil DOM and was affected by
      vegetation type and WFPS singly and interactively. The results implied that
      forest soils with more than 50% WFPS before winter freezing could release large
      amounts of fulvic acid-like DOM, which would be easily biodegraded and emitted as
      CO2 or run off with ground water during spring snow thaw.

PMID- 28743997
TI  - High-throughput analysis of the satellitome revealed enormous diversity of
      satellite DNAs in the neo-Y chromosome of the cricket Eneoptera surinamensis.
AB  - Satellite DNAs (satDNAs) constitute large portion of eukaryote genomes,
      comprising non-protein-coding sequences tandemly repeated. They are mostly found
      in heterochromatic regions of chromosomes such as around centromere or near
      telomeres, in intercalary heterochromatin, and often in non-recombining segments
      of sex chromosomes. We examined the satellitome in the cricket Eneoptera
      surinamensis (2n = 9, neo-X1X2Y, males) to characterize the molecular evolution
      of its neo-sex chromosomes. To achieve this, we analyzed illumina reads using
      graph-based clustering and complementary analyses. We found an unusually high
      number of 45 families of satDNAs, ranging from 4 bp to 517 bp, accounting for
      about 14% of the genome and showing different modular structures and high
      diversity of arrays. FISH mapping revealed that satDNAs are located mostly in C
      positive pericentromeric regions of the chromosomes. SatDNAs enrichment was also
      observed in the neo-sex chromosomes in comparison to autosomes. Especially
      astonishing accumulation of satDNAs loci was found in the highly differentiated
      neo-Y, including 39 satDNAs over-represented in this chromosome, which is the
      greatest satDNAs diversity yet reported for sex chromosomes. Our results suggest
      possible involvement of satDNAs in genome increasing and in molecular
      differentiation of the neo-sex chromosomes in this species, contributing to the
      understanding of sex chromosome composition and evolution in Orthoptera.

PMID- 28743998
TI  - Rapid evolution of a Batesian mimicry trait in a butterfly responding to arrival
      of a new model.
AB  - Batesian mimicry, a phenomenon in which harmless organisms resemble harmful or
      unpalatable species, has been extensively studied in evolutionary biology. Model
      species may differ from population to population of a single mimetic species, so
      different predation pressures might have driven micro-evolution towards better
      mimicry among regions. However, there is scant direct evidence of micro
      evolutionary change over time in mimicry traits. Papilio polytes shows female
      limited Batesian mimicry. On Okinawa, one mimicry model is Pachliopta
      aristolochiae, which was not present on the island until 1993. In P. polytes, the
      size of the hind-wing white spot, a mimetic trait, is maternally heritable. Among
      specimens collected between 1961 and 2016, the average white spot size was
      unchanged before the model's arrival but has rapidly increased since then.
      However, white spot size showed greater variance after the model's establishment
      than before. This suggests that before 1993, white spot size in this population
      was not selectively neutral but was an adaptive trait for mimicking an
      unpalatable native, Byasa alcinous, which looks like P. aristolochiae apart from
      the latter's hind-wing white spot. Thus, some females switched their model to the
      new one after its arrival.

PMID- 28743999
TI  - Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1
      targeted inhibition and signaling crosstalk.
AB  - Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key
      role in regulating intracellular redox status. Selenocystine (SeC) a natural
      available Se-containing amino acid showed novel anticancer potential through
      triggering oxidative damage-mediated apoptosis. However, whether TrxR-mediated
      oxidative damage was involved in SeC-induced apoptosis in human glioma cells has
      not been elucidated yet. Herein, SeC-induced human glioma cell apoptosis was
      detected in vitro, accompanied by PARP cleavage, caspases activation and DNA
      fragmentation. Mechanically, SeC caused mitochondrial dysfunction and imbalance
      of Bcl-2 family expression. SeC treatment also triggered ROS-mediated DNA damage
      and disturbed the MAPKs and AKT pathways. However, inhibition of ROS
      overproduction effectively attenuated SeC-induced oxidative damage and apoptosis,
      and normalized the expression of MAPKs and AKT pathways, indicating the
      significance of ROS in SeC-induced apoptosis. Importantly, U251 human glioma
      xenograft growth in nude mice was significantly inhibited in vivo. Further
      investigation revealed that SeC-induced oxidative damage was achieved by TrxR1
      targeted inhibition in vitro and in vivo. Our findings validated the potential of
      SeC to inhibit human glioma growth by oxidative damage-mediated apoptosis through
      triggering TrxR1-targeted inhibition.

PMID- 28744000
TI  - Permeability Barrier and Microstructure of Skin Lipid Membrane Models of Impaired
      Glucosylceramide Processing.
AB  - Ceramide (Cer) release from glucosylceramides (GlcCer) is critical for the
      formation of the skin permeability barrier. Changes in beta-glucocerebrosidase
      (GlcCer'ase) activity lead to diminished Cer, GlcCer accumulation and structural
      defects in SC lipid lamellae; however, the molecular basis for this impairment is
      not clear. We investigated impaired GlcCer-to-Cer processing in human Cer
      membranes to determine the physicochemical properties responsible for the barrier
      defects. Minor impairment (5-25%) of the Cer generation from GlcCer decreased the
      permeability of the model membrane to four markers and altered the membrane
      microstructure (studied by X-ray powder diffraction and infrared spectroscopy),
      in agreement with the effects of topical GlcCer in human skin. At these
      concentrations, the accumulation of GlcCer was a stronger contributor to this
      disturbance than the lack of human Cer. However, replacement of 50-100% human Cer
      by GlcCer led to the formation of a new lamellar phase and the maintenance of a
      rather good barrier to the four studied permeability markers. These findings
      suggest that the major cause of the impaired water permeability barrier in
      complete GlcCer'ase deficiency is not the accumulation of free GlcCer but other
      factors, possibly the retention of GlcCer bound in the corneocyte lipid envelope.

PMID- 28744001
TI  - An intrinsic mechanism controls reactivation of neural stem cells by spindle
      matrix proteins.
AB  - The switch between quiescence and proliferation is central for neurogenesis and
      its alteration is linked to neurodevelopmental disorders such as microcephaly.
      However, intrinsic mechanisms that reactivate Drosophila larval neural stem cells
      (NSCs) to exit from quiescence are not well established. Here we show that the
      spindle matrix complex containing Chromator (Chro) functions as a key intrinsic
      regulator of NSC reactivation downstream of extrinsic insulin/insulin-like growth
      factor signalling. Chro also prevents NSCs from re-entering quiescence at later
      stages. NSC-specific in vivo profiling has identified many downstream targets of
      Chro, including a temporal transcription factor Grainy head (Grh) and a neural
      stem cell quiescence-inducing factor Prospero (Pros). We show that spindle matrix
      proteins promote the expression of Grh and repress that of Pros in NSCs to govern
      their reactivation. Our data demonstrate that nuclear Chro critically regulates
      gene expression in NSCs at the transition from quiescence to proliferation.The
      spindle matrix proteins, including Chro, are known to regulate mitotic spindle
      assembly in the cytoplasm. Here the authors show that in Drosophila larval brain,
      Chro promotes neural stem cell (NSC) reactivation and prevents activated NSCs
      from entering quiescence, and that Chro carries out such a role by regulating the
      expression of key transcription factors in the nucleus.

PMID- 28744002
TI  - Evidence for the effect of depth on visual working memory.
AB  - Visual working memory (VWM) is a cognitive memory buffer for temporarily holding,
      processing, and manipulating visual information. Previous studies have
      demonstrated mixed results of the effect of depth perception on VWM, with some
      showing a beneficial effect while others not. In this study, we employed an
      adapted change detection paradigm to investigate the effects of two depth cues,
      binocular disparity and relative size. The memory array consisted of a set of
      pseudo-randomly positioned colored items, and the task was to judge whether the
      test item was changed compared to the memory item after a retention interval. We
      found that presenting the items in stereoscopic depth alone hardly affected VWM
      performance. When combining the two coherent depth cues, a significant larger VWM
      capacity of the perceptually closer-in-depth items was observed than that of the
      farther items, but the capacity for the two-depth-planes condition was not
      significantly different from that for the one-plane condition. Conflicting the
      two depth cues resulted in cancelling the beneficial effect of presenting items
      at a closer depth plane. The results indicate that depth perception could affect
      VWM, and the visual system may have an advantage in maintaining closer-in-depth
      objects in working memory.

PMID- 28744003
TI  - A sensitive acupuncture needle microsensor for real-time monitoring of nitric
      oxide in acupoints of rats.
AB  - This study reports an acupuncture needle modified with an iron-porphyrin
      functionalized graphene composite (FGPC) for real-time monitoring of nitric oxide
      (NO) release in acupoints of rats. A gold film was first deposited to the needle
      surface to enhance the conductivity. The FGPC was prepared via hydrothermal
      synthesis, and subsequently applied to the tip surface of acupuncture needle by
      electrochemical deposition method. The functionalized needle enabled a specific
      and sensitive detection of NO based on the favorably catalytic properties of iron
      porphyrin and the excellent conductivity of graphene. Amperometric data showed
      that the needle achieved not only a low detection limit down to 3.2 nM in PBS
      solution, but also a satisfactory selectivity. Interestingly, the functionalized
      needle could be inserted into the acupoints of rats for real-time monitoring of
      NO in vivo. It was found that a remarkable response to NO was respectively
      obtained in different acupoints when stimulated by L-arginine (L-Arg), revealing
      that the release of NO was detectable in acupoints. We expect this work would
      showcase the applications of acupuncture needle in detecting some important
      signaling molecules in vivo, and exploring the mechanism of acupuncture
      treatment.

PMID- 28744004
TI  - Sirt1 negatively regulates FcepsilonRI-mediated mast cell activation through AMPK
      and PTP1B-dependent processes.
AB  - Sirt1, a key regulator of metabolism and longevity, has recently been implicated
      in the regulation of allergic reactions, although the underlying mechanism
      remains unclear. Here we show that Sirt1 negatively regulates FcepsilonRI
      stimulated mast cell activation and anaphylaxis through two mutually regulated
      pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine
      phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK
      dependent suppression of FcepsilonRI signaling, thereby augmenting mast cell
      activation both in vitro and in vivo. Sirt1 inhibition of FcepsilonRI signaling
      also involved an alternative component, PTP1B, which attenuated the inhibitory
      AMPK pathway and conversely enhanced the stimulatory Syk pathway, uncovering a
      novel role of this phosphatase. Moreover, a Sirt1 activator resveratrol
      stimulated the inhibitory AMPK axis, with reciprocal suppression of the
      stimulatory PTP1B/Syk axis, thus potently inhibiting anaphylaxis. Overall, our
      results provide a molecular explanation for the beneficial role of Sirt1 in
      allergy and underscore a potential application of Sirt1 activators as a new class
      of anti-allergic agents.

PMID- 28744005
TI  - Modeling of an Inverted Drift Tube for Improved Mobility Analysis of Aerosol
      Particles.
AB  - A new mobility particle analyzer, which has been termed Inverted Drift Tube, has
      been modeled analytically as well as numerically and proven to be a very capable
      instrument. The basis for the new design have been the shortcomings of the
      previous ion mobility spectrometers, in particular (a) diffusional broadening
      which leads to degradation of instrument resolution and (b) inadequate low and
      fixed resolution (not mobility dependent) for large sizes. To overcome the
      diffusional broadening and have a mobility based resolution, the IDT uses two
      varying controllable opposite forces, a flow of gas with velocity v gas , and a
      linearly increasing electric field that opposes the movement. A new parameter,
      the separation ratio Lambda = v drift /v gas , is employed to determine the best
      possible separation for a given set of nanoparticles. Due to the system's need to
      operate at room pressure, two methods of capturing the ions at the end of the
      drift tube have been developed, Intermittent Push Flow for a large range of
      mobilities, and Nearly-Stopping Potential Separation, with very high separation
      but limited only to a narrow mobility range. A chromatography existing concept of
      resolving power is used to differentiate between peak resolution in the IDT and
      acceptable separation between similar mobility sizes.

PMID- 28744006
TI  - Association of human height-related genetic variants with familial short stature
      in Han Chinese in Taiwan.
AB  - Human height can be described as a classical and inherited trait model. Genome
      wide association studies (GWAS) have revealed susceptible loci and provided
      insights into the polygenic nature of human height. Familial short stature (FSS)
      represents a suitable trait for investigating short stature genetics because
      disease associations with short stature have been ruled out in this case. In
      addition, FSS is caused only by genetically inherited factors. In this study, we
      explored the correlations of FSS risk with the genetic loci associated with human
      height in previous GWAS, alone and cumulatively. We systematically evaluated 34
      known human height single nucleotide polymorphisms (SNPs) in relation to FSS in
      the additive model (p < 0.00005). A cumulative effect was observed: the odds
      ratios gradually increased with increasing genetic risk score quartiles (p <
      0.001; Cochran-Armitage trend test). Six affected genes-ZBTB38, ZNF638, LCORL,
      CABLES1, CDK10, and TSEN15-are located in the nucleus and have been implicated in
      embryonic, organismal, and tissue development. In conclusion, our study suggests
      that 13 human height GWAS-identified SNPs are associated with FSS risk both alone
      and cumulatively.

PMID- 28744007
TI  - Molecular recognition by multiple metal coordination inside wavy-stacked
      macrocycles.
AB  - Most biological and synthetic receptors for small organic molecules employ a
      combination of relatively weak intermolecular interactions such as hydrogen
      bonds. A host compound that utilizes stronger yet reversible bonding in a
      synergistic manner could realize precise recognition, but the regulation and
      spatial arrangement of such reactive interaction moieties have been a challenge.
      Here, we show a multinuclear zinc complex synthesized from a macrocyclic ligand
      hexapap, which inwardly arranges labile metal coordination sites for external
      molecules. The metallomacrocycle forms a unique wavy-stacked structure upon
      binding a suitable length of dicarboxylic acids via multipoint coordination
      bonding. The saddle-shaped deformation and dimerization realize the
      differentiation of the interaction moieties, and change of guest-binding modes at
      specific metal coordination sites among the many present have been achieved
      utilizing acid/base as external stimuli.Synergistic use of coordination bonds
      that are strong and reversible realizes unique molecular recognition in
      artificial systems. Here, the authors show that a zinc-based metallomacrocyle can
      bind dicarboxylic acids of suitable length at specific metal sites by shape
      deformation and dimerization.

PMID- 28744008
TI  - Interaction of hydrophobic polymers with model lipid bilayers.
AB  - The interaction of nanoscale synthetic materials with cell membranes is one of
      the key steps determining nanomaterials' toxicity. Here we use molecular
      simulations, with atomistic and coarse-grained resolution, to investigate the
      interaction of three hydrophobic polymers with model lipid membranes. Polymer
      nanoparticles made of polyethylene (PE), polypropylene (PP) and polystyrene with
      size up to 7 nm enter easily POPC lipid membranes, localizing to the membrane
      hydrophobic core. For all three materials, solid polymeric nanoparticles become
      essentially liquid within the membrane at room temperature. Still, their behavior
      in the membrane core is not the same: PP and PS disperse in the core of the
      bilayer, while PE shows a tendency to aggregate. We also examined the interaction
      of the polymers with heterogeneous membranes, consisting of a ternary lipid
      mixture exhibiting liquid-ordered/liquid-disordered phase separation. The
      behavior of the three polymers is markedly different: PP disfavors lipid phase
      separation, PS stabilizes it, and PE modifies the topology of the phase
      boundaries and causes cholesterol depletion from the liquid ordered phase. Our
      results show that different hydrophobic polymers have major effects on the
      properties of lipid membranes, calling for further investigations on model
      systems and cell membranes.

PMID- 28744009
TI  - Efficacy and safety of midostaurin in patients with advanced systemic
      mastocytosis: 10-year median follow-up of a phase II trial.
AB  - Patients with advanced systemic mastocytosis (SM) (e.g. aggressive SM (ASM), SM
      with an associated hematologic neoplasm (SM-AHN) and mast cell leukemia (MCL))
      have limited treatment options and exhibit reduced survival. Midostaurin is an
      oral multikinase inhibitor that inhibits D816V-mutated KIT, a primary driver of
      SM pathogenesis. We conducted a phase II trial of midostaurin 100 mg twice daily,
      administered as 28-day cycles, in 26 patients (ASM, n=3; SM-AHN, n= 17; MCL, n=6)
      with at least one sign of organ damage. During the first 12 cycles, the overall
      response rate was 69% (major/partial response: 50/19%) with clinical benefit in
      all advanced SM variants. With ongoing therapy, 2 patients achieved a complete
      remission of their SM. Midostaurin produced a ?50% reduction in bone marrow mast
      cell burden and serum tryptase level in 68% and 46% of patients, respectively.
      Median overall survival for the entire cohort was 40 months, and 18.5 months for
      MCL patients. Low-grade gastrointestinal side effects were common and manageable
      with antiemetics. The most frequent grade 3/4 nonhematologic and hematologic
      toxicities were asymptomatic hyperlipasemia (15%) and anemia (12%). With median
      follow-up of 10 years, no unexpected toxicities emerged. These data establish the
      durable activity and tolerability of midostaurin in advanced SM.

PMID- 28744010
TI  - The JAK2V617F-bearing vascular niche promotes clonal expansion in
      myeloproliferative neoplasms.
AB  - The acquired kinase mutation JAK2V617F plays a central role in myeloproliferative
      neoplasms (MPNs). However, the mechanisms responsible for the malignant
      hematopoietic stem/progenitor cell (HSPC) expansion seen in patients with MPNs
      are not fully understood, limiting the effectiveness of current treatment.
      Endothelial cells (ECs) are an essential component of the hematopoietic niche,
      and they have been shown to express the JAK2V617F mutation in patients with MPNs.
      We show that the JAK2V617F-bearing vascular niche promotes the expansion of the
      JAK2V617F HSPCs in preference to JAK2WT HSPCs, potentially contributing to poor
      donor cell engraftment and disease relapse following stem cell transplantation.
      The expression of Chemokine (C-X-C motif) ligand 12 (CXCL12) and stem cell factor
      (SCF) were upregulated in JAK2V617F-bearing ECs compared to wild-type ECs,
      potentially accounting for this observation. We further identify that the
      thrombopoietin (TPO)/MPL signaling pathway is critical for the altered vascular
      niche function. A better understanding of how the vascular niche contributes to
      HSPC expansion and MPN development is essential for the design of more effective
      therapeutic strategies for patients with MPNs.

PMID- 28744011
TI  - NK cell dynamics and association with molecular response in early chronic phase
      chronic myelogenous leukemia (CML-CP) patients treated with nilotinib.

PMID- 28744012
TI  - B7-H4 enhances the differentiation of murine leukemia-initiating cells via the
      PTEN/AKT/RCOR2/RUNX1 pathways.

PMID- 28744013
TI  - The T-cell leukemia-associated ribosomal RPL10 R98S mutation enhances JAK-STAT
      signaling.
AB  - Several somatic ribosome defects have recently been discovered in cancer, yet
      their oncogenic mechanisms remain poorly understood. Here we investigated the
      pathogenic role of the recurrent R98S mutation in ribosomal protein L10 (RPL10
      R98S) found in T-cell acute lymphoblastic leukemia (T-ALL). The JAK-STAT
      signaling pathway is a critical controller of cellular proliferation and
      survival. A proteome screen revealed overexpression of several Jak-Stat signaling
      proteins in engineered RPL10 R98S mouse lymphoid cells, which we confirmed in
      hematopoietic cells from transgenic Rpl10 R98S mice and T-ALL xenograft samples.
      RPL10 R98S expressing cells displayed JAK-STAT pathway hyper-activation upon
      cytokine stimulation, as well as increased sensitivity to clinically used JAK
      STAT inhibitors like pimozide. A mutually exclusive mutation pattern between
      RPL10 R98S and JAK-STAT mutations in T-ALL patients further suggests that RPL10
      R98S functionally mimics JAK-STAT activation. Mechanistically, besides
      transcriptional changes, RPL10 R98S caused reduction of apparent programmed
      ribosomal frameshifting at several ribosomal frameshift signals in mouse and
      human Jak-Stat genes, as well as decreased Jak1 degradation. Of further medical
      interest, RPL10 R98S cells showed reduced proteasome activity and enhanced
      sensitivity to clinical proteasome inhibitors. Collectively, we describe
      modulation of the JAK-STAT cascade as a novel cancer-promoting activity of a
      ribosomal mutation, and expand the relevance of this cascade in leukemia.

PMID- 28744014
TI  - Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms:
      association with age, hydroxyurea administration, disease type and JAK2
      mutational status.
AB  - The multistep process of TP53 mutation expansion during myeloproliferative
      neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been
      documented retrospectively. It is currently unknown how common TP53 mutations
      with low variant allele frequency (VAF) are, whether they are linked to
      hydroxyurea (HU) cytoreduction, and what disease progression risk they carry.
      Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated
      with HU, interferon alpha-2a or anagrelide and 85 untreated patients. We found
      TP53 mutations in 50 cases (0.2-16.3% VAF), regardless of disease subtype, driver
      gene status and cytoreduction. Both therapy and TP53 mutations were strongly
      associated with older age. Over-time analysis showed that the mutations may be
      undetectable at diagnosis and slowly increase during disease course. Although
      three patients with TP53 mutations progressed to TP53-mutated or TP53-wild-type
      AML, we did not observe a significant age-independent impact on overall survival
      during the follow-up. Further, we showed that complete p53 inactivation alone led
      to neither blast transformation nor HU resistance. Altogether, we revealed
      patient's age as the strongest factor affecting low-burden TP53 mutation
      incidence in MPN and found no significant age-independent association between
      TP53 mutations and hydroxyurea. Mutations may persist at low levels for years
      without an immediate risk of progression.

PMID- 28744015
TI  - Lactate oxidation facilitates growth of Mycobacterium tuberculosis in human
      macrophages.
AB  - Mycobacterium tuberculosis (Mtb) uses alveolar macrophages as primary host cells
      during infection. In response to an infection, macrophages switch from pyruvate
      oxidation to reduction of pyruvate into lactate. Lactate might present an
      additional carbon substrate for Mtb. Here, we demonstrate that Mtb can utilize L
      lactate as sole carbon source for in vitro growth. Lactate conversion is strictly
      dependent on one of two potential L-lactate dehydrogenases. A knock-out mutant
      lacking lldD2 (Rv1872c) was unable to utilize L-lactate. In contrast, the lldD1
      (Rv0694) knock-out strain was not affected in growth on lactate and retained full
      enzymatic activity. On the basis of labelling experiments using [U-13C3]-L
      lactate as a tracer the efficient uptake of lactate by Mtb and its conversion
      into pyruvate could be demonstrated. Moreover, carbon flux from lactate into the
      TCA cycle, and through gluconeogenesis was observed. Gluconeogenesis during
      lactate consumption depended on the phosphoenolpyruvate carboxykinase, a key
      enzyme for intracellular survival, showing that lactate utilization requires
      essential metabolic pathways. We observed that the DeltalldD2 mutant was impaired
      in replication in human macrophages, indicating a critical role for lactate
      oxidation during intracellular growth.

PMID- 28744016
TI  - Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine
      hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes.
AB  - 3-Deazaneplanocin A (DZNep) is an inhibitor of S-Adenosyl-L-Homocysteine
      Hydrolase (SAHH) known to inhibit EZH2, a histone methylase upregulated during
      osteoarthritis. In this study, we assessed its effects in human articular
      chondrocytes. Anti-inflammatory effects were assessed by Nitric Oxide (NO),
      Prostaglandin E2 (PGE2) and Metalloprotease (MMP) release in IL-1beta-stimulated
      chondrocytes. MAPK and NFkappaB activation was analyzed by western blotting.
      Differentially expressed genes (DEG) regulated by DZNep were identified by whole
      transcriptome microarray. DZNep inhibited SAHH activity and was not toxic. It
      counteracted NO, PGE2 and MMP release, and reduced MAPK activation induced by IL
      1beta. By whole-transcriptome analysis, we identified that DNZep counteracts the
      effect of IL-1beta on the expression of 81 protein-coding genes, including
      CITED2, an MMP inhibitor. These genes are organized in a protein-protein network
      centred on EGR1, which is known to functionally interact with EZH2. Gene
      ontologies enrichment analysis confirmed that DZNep counteracts IL-1beta-induced
      expression of genes involved in cartilage matrix breakdown (MMPs and ADAMTS). In
      addition, DZNep up-regulated cartilage specific genes, such as COL2A1 and SOX9,
      suggesting a chondroprotective effect of DZNep. DZNep exhibits anti-inflammatory
      effects, and regulates genes implicated in chondroprotective response in human
      articular chondrocytes, suggesting that inhibitors of S-adenosylmethionine
      dependent methyltransferases could be effective treatments for OA.

PMID- 28744017
TI  - Spin caloritronic nano-oscillator.
AB  - Energy loss due to ohmic heating is a major bottleneck limiting down-scaling and
      speed of nano-electronic devices, and harvesting ohmic heat for signal processing
      is a major challenge in modern electronics. Here, we demonstrate that thermal
      gradients arising from ohmic heating can be utilized for excitation of coherent
      auto-oscillations of magnetization and for generation of tunable microwave
      signals. The heat-driven dynamics is observed in Y3Fe5O12/Pt bilayer nanowires
      where ohmic heating of the Pt layer results in injection of pure spin current
      into the Y3Fe5O12 layer. This leads to excitation of auto-oscillations of the
      Y3Fe5O12 magnetization and generation of coherent microwave radiation. Our work
      paves the way towards spin caloritronic devices for microwave and magnonic
      applications.Harvesting ohmic heat for signal processing is one of major
      challenges in modern electronics and spin caloritronics, but not yet well
      accomplished. Here the authors demonstrate a spin torque oscillator device driven
      by pure spin current arising from thermal gradient across an Y3Fe5O12/Pt
      interface.

PMID- 28744018
TI  - CXCL10 is produced in hepatitis A virus-infected cells in an IRF3-dependent but
      IFN-independent manner.
AB  - Acute hepatitis A caused by hepatitis A virus (HAV) infection is accompanied by
      severe liver injury in adult patients, and the liver injury is associated with
      the production of chemokines. Herein, we investigated the mechanism of how HAV
      infection induces the production of CXCR3 and CCR5 chemokines, such as CXCL10,
      CCL4 and CCL5. The production of CXCL10, CCL4 and CCL5 was markedly increased by
      HAV (HM-175/18f) infection in the culture of primary human hepatocytes and HepG2
      cells. In particular, CXCL10 was produced in HAV-infected cells, not in
      neighboring uninfected cells. Moreover, these chemokines were significantly
      increased in the sera of acute hepatitis A patients. The production of IFN
      lambdas was also robustly induced by HAV infection, and the blocking of secreted
      IFN-lambdas partially abrogated the production of CCL4 and CCL5 in HAV-infected
      cells. However, CXCL10 production was not decreased by the blocking of IFN
      lambdas. Instead, CXCL10 production was reduced by silencing the expression of
      RIG-I-like receptor (RLR) signal molecules, such as mitochondrial antiviral
      signaling protein and interferon regulatory factor 3, in HAV-infected cells. In
      conclusion, HAV infection strongly induces the production of helper 1 T cell
      associated chemokines, particularly CXCL10 via RLR signaling, even without
      secreted IFNs.

PMID- 28744019
TI  - Estrogen Regulates Bone Turnover by Targeting RANKL Expression in Bone Lining
      Cells.
AB  - Estrogen is critical for skeletal homeostasis and regulates bone remodeling, in
      part, by modulating the expression of receptor activator of NF-kappaB ligand
      (RANKL), an essential cytokine for bone resorption by osteoclasts. RANKL can be
      produced by a variety of hematopoietic (e.g. T and B-cell) and mesenchymal
      (osteoblast lineage, chondrocyte) cell types. The cellular mechanisms by which
      estrogen acts on bone are still a matter of controversy. By using murine
      reconstitution models that allow for selective deletion of estrogen receptor
      alpha (ERalpha) or selective inhibition of RANKL in hematopoietic vs. mesenchymal
      cells, in conjunction with in situ expression profiling in bone cells, we
      identified bone lining cells as important gatekeepers of estrogen-controlled bone
      resorption. Our data indicate that the increase in bone resorption observed in
      states of estrogen deficiency in mice is mainly caused by lack of ERalpha
      mediated suppression of RANKL expression in bone lining cells.

PMID- 28744020
TI  - Inflammatory potential of diet and risk of cardiovascular disease or mortality: A
      meta-analysis.
AB  - Inconsistent findings have reported on the inflammatory potential of diet and
      cardiovascular disease (CVD) and mortality risk. The aim of this meta-analysis
      was to investigate the association between the inflammatory potential of diet as
      estimated by the dietary inflammatory index (DII) score and CVD or mortality risk
      in the general population. A comprehensive literature search was conducted in
      PubMed and Embase databases through February 2017. All prospective observational
      studies assessing the association of inflammatory potential of diet as estimated
      by the DII score with CVD and all-cause, cancer-related, cardiovascular mortality
      risk were included. Nine prospective studies enrolling 134,067 subjects were
      identified. Meta-analyses showed that individuals with the highest category of
      DII (maximal pro-inflammatory) was associated with increased risk of all-cause
      mortality (hazard risk [HR] 1.22; 95% confidence interval [CI] 1.06-1.41),
      cardiovascular mortality (RR 1.24; 95% CI 1.01-1.51), cancer-related mortality
      (RR 1.28; 95% CI 1.04-1.58), and CVD (RR 1.32; 95% CI 1.09-1.60) than the lowest
      DII score. More pro-inflammatory diets, as estimated by the higher DII score are
      independently associated with an increased risk of all-cause, cardiovascular,
      cancer-related mortality, and CVD in the general population, highlighting low
      inflammatory potential diet may reduce mortality and CVD risk.

PMID- 28744022
TI  - Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from
      E. coli is less effective than Polyethylene Glycol-conjugated GCSF.
AB  - Human granulocyte colony-stimulating factor (GCSF) is a well-known cytokine for
      neutropenia treatment. However, daily injections are required due to the short
      circulating half-life of the protein. To overcome this bottleneck, we fused GCSF
      with the Fc domain of IgG1 at the C terminus (GCSF-Fc) and with the maltose
      binding protein (MBP) tag at the N-terminus and expressed it as a soluble protein
      in the cytoplasm of E. coli. We also conjugated PEG aldehyde to GCSF to make PEG
      GCSF. The bioactivities of GCSF-Fc and PEG-GCSF were similar to native GCSF using
      the mouse M-NFS-60 myelogenous leukemia cell line. The EC50 dose-response curves
      for GCSF, GCSF-Fc and PEG-GCSF were 37 +/- 12 pM, 75 +/- 13.5 pM and 46 +/- 5.5
      pM, respectively. When the proteins were injected into neutropenic rats, the
      group injected with PEG-GCSF showed the highest and fastest recovery of
      neutrophils, followed by GCSF-Fc and GCSF. ELISA assay revealed the PEG-GCSF had
      the longest plasma circulation (>72 h), followed by GCSF-Fc (>48 h) and GCSF (~24
      h), which is consistent with the in vivo activities of the proteins. In summary,
      the GCSF-Fc purified from E. coli was not as efficient as PEG-GCSF in treating
      neutropenic rats.

PMID- 28744021
TI  - Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis.
AB  - Cancer-associated fibroblasts (CAFs) regulate diverse intratumoral biological
      programs and can promote or inhibit tumorigenesis, but those CAF populations that
      negatively impact the clinical outcome of lung cancer patients have not been
      fully elucidated. Because Thy-1 (CD90) marks CAFs that promote tumor cell
      invasion in a murine model of KrasG12D-driven lung adenocarcinoma (KrasLA1), here
      we postulated that human lung adenocarcinomas containing Thy-1+ CAFs have a worse
      prognosis. We first examined the location of Thy-1+ CAFs within human lung
      adenocarcinomas. Cells that co-express Thy-1 and alpha-smooth muscle actin
      (alphaSMA), a CAF marker, were located on the tumor periphery surrounding
      collectively invading tumor cells and in perivascular regions. To interrogate a
      human lung cancer database for the presence of Thy-1+ CAFs, we isolated Thy-1+
      CAFs and normal lung fibroblasts (LFs) from the lungs of KrasLA1 mice and wild
      type littermates, respectively, and performed global proteomic analysis on the
      murine CAFs and LFs, which identified 425 proteins that were differentially
      expressed. Used as a probe to identify Thy-1+ CAF-enriched tumors in a compendium
      of 1,586 lung adenocarcinomas, the presence of the 425-gene signature predicted a
      significantly shorter survival. Thus, Thy-1 marks a CAF population that adversely
      impacts clinical outcome in human lung cancer.

PMID- 28744023
TI  - Forest productivity mitigates human disturbance effects on late-seral prey
      exposed to apparent competitors and predators.
AB  - Primary production can determine the outcome of management actions on ecosystem
      properties, thereby defining sustainable management. Yet human agencies commonly
      overlook spatio-temporal variations in productivity by recommending fixed
      resource extraction thresholds. We studied the influence of forest productivity
      on habitat disturbance levels that boreal caribou - a threatened, late-seral
      ungulate under top-down control - should be able to withstand. Based on 10 years
      of boreal caribou monitoring, we found that adult survival and recruitment to
      populations decreased with landscape disturbance, but increased with forest
      productivity. This benefit of productivity reflected the net outcome of an
      increase in resources for apparent competitors and predators of caribou, and a
      more rapid return to the safety of mature conifer forests. We estimated 3-fold
      differences in forest harvesting levels that caribou populations could withstand
      due to variations in forest productivity. The adjustment of ecosystem
      provisioning services to local forest productivity should provide strong
      conservation and socio-economic advantages.

PMID- 28744024
TI  - Recent increased identification and transmission of HIV-1 unique recombinant
      forms in Sweden.
AB  - A temporal increase in non-B subtypes has earlier been described in Sweden by us
      and we hypothesized that this increased viral heterogeneity may become a hotspot
      for the development of more complex and unique recombinant forms (URFs) if the
      epidemics converge. In the present study, we performed subtyping using four
      automated tools and phylogenetic analysis by RAxML of pol gene sequences (n =
      5246) and HIV-1 near full-length genome (HIV-NFLG) sequences (n = 104). A CD4+ T
      cell decline trajectory algorithm was used to estimate time of HIV infection.
      Transmission clusters were identified using the family-joining method. The
      analysis of HIV-NFLG and pol gene described 10.6% (11/104) and 2.6% (137/5246) of
      the strains as URFs, respectively. An increasing trend of URFs was observed in
      recent years by both approaches (p = 0.0082; p < 0.0001). Transmission cluster
      analysis using the pol gene of all URFs identified 14 clusters with two to eight
      sequences. Larger transmission clusters of URFs (BF1 and 01B) were observed among
      MSM who mostly were sero-diagnosed in recent time. Understanding the increased
      appearance and transmission of URFs in recent years could have importance for
      public health interventions and the use of HIV-NFLG would provide better
      statistical support for such assessments.

PMID- 28744025
TI  - Genetic loci associated with an earlier age at onset in multiplex schizophrenia.
AB  - An earlier age at onset (AAO) has been associated with greater genetic loadings
      in schizophrenia. This study aimed to identify modifier loci associated with an
      earlier AAO of schizophrenia. A genome-wide association analysis (GWAS) was
      conducted in 94 schizophrenia probands with the earliest AAO and 91 with the
      latest AAO. Candidate single nucleotide polymorphisms (SNPs) were then genotyped
      in the co-affected siblings and unrelated probands. Multi-SNP genetic risk scores
      (GRS) composed of the candidate loci were used to distinguish patients with an
      early or late AAO. The 14-SNP GRS could distinguish the co-affected siblings (n =
      90) of the earliest probands from those (n = 91) of the latest probands. When 132
      patients with an earlier AAO and 158 patients with a later AAO were included, a
      significant trend in the 14-SNP GRS was detected among those unrelated probands
      from 4 family groups with the earliest, earlier, later, and latest AAO. The
      overall effect of the 14 SNPs on an AAO in schizophrenia was verified using co
      affected siblings of the GWAS probands and trend effect across unrelated
      patients. Preliminary network analysis of these loci revealed the involvement of
      PARK2, a gene intensively reported in Parkinson's disease and schizophrenia
      research.

PMID- 28744026
TI  - Integrin beta3/Akt signaling contributes to platelet-induced hemangioendothelioma
      growth.
AB  - Hemangioendothelioma (HE) is a type of angiomatous lesions that features
      endothelial cell proliferation. Understanding the mechanisms orchestrating HE
      angiogenesis can provide therapeutic insights. It has been shown that platelets
      can support normal and malignant endothelial cells during angiogenesis. Using the
      mouse endothelial-derived EOMA cell line as a model of HE, we explored the
      regulatory effect of platelets. We found that platelets stimulated EOMA
      proliferation but did not mitigate apoptosis. Furthermore, direct platelet-EOMA
      cell contact was required and the proliferation was mediated via integrin
      beta3/Akt signaling in EOMA cells. SiRNA knockdown of integrin beta3 and
      inhibition of Akt activity significantly abolished platelet-induced EOMA cell
      proliferation in vitro and tumor development in vivo. These results provide a new
      mechanism by which platelets support HE progression and suggest integrin beta3 as
      a potential target to treat HE.

PMID- 28744027
TI  - The Effect of Ultraviolet B on Fibrillin-1 and Fibrillin-2 in Human Non-pigmented
      Ciliary Epithelial Cells In Vitro.
AB  - The ciliary zonules link the lens to the ciliary body in the eye, controlling the
      thickness of the lens for focusing through their characteristic elasticity. The
      ciliary zonules are composed of oxytalan fibers. Physiological or pathological
      damage to the ciliary zonules, including exposure to ultraviolet (UV)-A and UV-B
      components, can lead to lens dislocation. However, no studies have shown whether
      UV affects the ciliary zonule. Here, we assessed the effects of UV light on human
      nonpigmented ciliary epithelial cells (HNPCECs). HNPCECs were cultured for 4
      weeks, and expression of fibrillin-1 and fibrillin-2 was confirmed. In control
      cultures (0 mJ/cm2), some fibrillin-1-positive fibers were merged with fibrillin
      2. After UV-A irradiation, the appearance of both fibrillin-1- and fibrillin-2
      positive fibers was unchanged. However, after UV-B irradiation, fibrillin-1
      positive fibers became thin at an irradiation level of 100 mJ/cm2, and the fiber
      structure became amorphous at 150 mJ/cm2. Fibrillin-2-positive fibers lost their
      continuity and disappeared after being exposed to 150 mJ/cm2 UV-B. UV-B
      irradiation did not affect cell viability, possibly because of the sensitivity of
      fibrillin-1 and fibrillin-2 to UV-B. Thus, dislocation of the lens with age may
      be attributable to cumulative exposure to UV-B.

PMID- 28744028
TI  - Expression of c-kit and Cytokeratin 5 in the Submandibular Gland after Release of
      Long-Term Ligation of the Main Excretory Duct in Mice.
AB  - Long-term submandibular duct obstruction is thought to cause irreversible atrophy
      and dysfunction of the submandibular gland. As an atrophic gland may be induced
      clinically by chronic or recurrent infection, it is generally removed surgically.
      However, the regenerative capacity of atrophic submandibular glands after long
      term obstruction is not completely understood. We studied the regenerative
      capacity of the mouse submandibular duct using an aneurysm clip ligation model.
      We documented changes in the size, histologic structure and gene expression of
      the submandibular gland after 2 months of ligation, and 1 week, 1 month and 2
      months after clip removal. Two months of ligation caused atrophy, particularly in
      the acinar portion. In the 2 months after clip removal, we observed a steady and
      significant increase in the expression of the acinar cell precursor gene
      cytokeratin 5 (CK5), and a significant decrease in the expression of the stem
      cell marker c-kit. These findings suggest that the submandibular gland retains
      some capacity for regeneration even after long-term obstruction, and that CK5
      could serve as a marker of this regenerative process.

PMID- 28744029
TI  - Physical activity level and fall risk among community-dwelling older adults.
AB  - [Purpose] To find the physical activity level and fall risk among the community
      dwelling Malaysian older adults and determine the correlation between them.
      [Subjects and Methods] A cross-sectional study was conducted in which, the
      physical activity level was evaluated using the Rapid Assessment of Physical
      Activity questionnaire and fall risk with Fall Risk Assessment Tool. Subjects
      recruited were 132 community-dwelling Malaysian older adults using the
      convenience sampling method. [Results] The majority of the participants were
      under the category of under-active regular light-activities and most of them
      reported low fall risk. The statistical analysis using Fisher's exact test did
      not show a significant correlation between physical activity level and fall risk.
      [Conclusion] The majority of community-dwelling Malaysian older adults are
      performing some form of physical activity and in low fall risk category. But this
      study did not find any significant correlation between physical activity level
      and fall risk among community-dwelling older adults in Malaysia.

PMID- 28744030
TI  - The effects of milk intake and whole-body vibration exercise on bone mineral
      density in elderly women in nursing homes.
AB  - [Purpose] This study was designed to investigate the effects of lactose-free milk
      intake and whole-body vibration exercises on bone density in elderly female
      nursing home residents who had difficulty exercising outdoors and had not
      consumed milk. [Subjects and Methods] Twenty seven elderly women aged 70 or older
      from 3 nursing homes located in Incheon, Korea participated in the study. The
      experimental group (n=13) carried out whole-body vibration exercises and drank
      lactose-free milk, while the control group (n=14) continued to live their
      ordinary nursing home lives. Weight, BMI, T-scores, and Z-scores were compared
      between the experimental and control groups after 12 weeks. [Results] The
      comparison of changes in weight and BMI in the control group before and after the
      12-week experiment found no statistically significant differences. However, bone
      mineral density was significantly different, with the T-score significantly
      decreasing from -2.99 to -3.48 and the Z-score decreasing from -1.87 to -2.58.
      The other comparisons of physical changes in the control group before and after
      the 12-week experiment found no statistical significance. [Conclusion] The
      results indicate that regular consumption of lactose-free milk and performing
      whole-body vibration exercises can delay the progression of bone density loss in
      older adults in nursing homes; adequate exercise and calcium intake could
      eventually help prevent fractures.

PMID- 28744031
TI  - Relationship of locomotive syndrome with health-related quality of life among
      patients with obstructive sleep apnea syndrome.
AB  - [Purpose] This study aimed to examine the prevalence of locomotive syndrome among
      patients with obstructive sleep apnea syndrome (OSAS) using the "loco-check"
      recently developed by the Japanese Orthopedic Association, and to compare health
      related quality of life (HRQOL) among patients with and without locomotive
      syndrome. [Subjects and Methods] This cross-sectional study evaluated 1,195
      outpatients with OSAS (1,030 males and 165 females). Locomotive syndrome was
      evaluated using the Japanese Orthopedic Association's "loco-check". HRQOL and
      psychological distress were evaluated using the EuroQol 5-dimensional (EQ-5D) and
      6-item Kessler questionnaires. [Results] Locomotive syndrome was detected in 578
      patients (48.4%), including 398 males (38.6% of males) and 119 females (70.3% of
      females). Patients with OSAS and locomotive syndrome had significantly lower EQ
      5D scores, compared to patients without locomotive syndrome. Multiple regression
      analysis revealed that HRQOL among patients with OSAS was independently
      associated with locomotive syndrome, age, gender, body mass index, apnea hypopnea
      index, the Japanese version of the Epworth Sleepiness Scale score, and exercise
      habits. [Conclusion] The prevalence of locomotive syndrome was thought to be
      comparatively high in patients with OSAS, and locomotive syndrome was associated
      with lower HRQOL, even after adjusting for confounding factors. Prevention or
      management of locomotive syndrome may be beneficial for improving HRQOL among
      patients with OSAS.

PMID- 28744032
TI  - Effect of a 4-week balance exercise with medio-lateral unstable sole on ankle
      joint functional ability.
AB  - [Purpose] This study examined the effects of 4-week of balance exercise with
      medio-lateral unstable sole on ankle muscle activation and functional ability.
      [Subjects and Methods] Thirty university students without current or past ankle
      injuries were assigned to either an experimental group or control group. The
      experimental group participated in a balance exercise program 3 times a week over
      4 weeks, which consisted of one-leg stands and semi-squat exercises with medio
      lateral unstable sole. The control group continued with their regular life
      activities without participation in the program. Electromyographic activities of
      peroneus longus and brevis muscles were recorded during stair descending
      immediately before and after the exercise program. Functional balance was tested
      with the Star Excursion Balance test immediately before and after the exercise
      program. Paired t-tests were used to assess statistical significance. [Results]
      Activation of peroneus longus and brevis and Star Excursion Balance Test scores
      in both groups did not show a significant difference between pre- and post
      exercise. [Conclusion] A future study is suggested with increased level of medio
      lateral perturbation during outcome measurements and exercises with addition of
      supervision in the exercise training and home program.

PMID- 28744033
TI  - The effect of cognitive-motor dual task training with the biorescue force
      platform on cognition, balance and dual task performance in institutionalized
      older adults: a randomized controlled trial.
AB  - [Purpose] This study investigates whether cognition, balance and dual task
      performance in institutionalized older adults improves by a virtual reality dual
      task training. [Subjects and Methods] Randomized controlled trial; Twenty
      institutionalized older adults with mild cognitive impairment (13 female, 7 male;
      average age, 87.2 +/- 5.96 years) were randomized to the intervention (i.e.
      Virtual reality dual-task training using the BioRescue) or control group (no
      additional training). The intervention group took part in a 6-week training
      program while the elderly in the control group maintained their daily activities.
      Balance was measured with the Instrumented Timed Up-and-Go Test with and without
      a cognitive task. The Observed Emotion Rating Scale and Intrinsic Motivation
      Inventory were administered to evaluate the emotions and motivation regarding the
      exergaming program. [Results] The intervention group improved significantly on
      the total Timed Up-and-Go duration and the turn-to-sit duration during single
      task walking in comparison to the control group who received no additional
      training. Participants found the virtual reality dual task training pleasant and
      useful for their concentration, memory and balance. Pleasure and alertness were
      the two emotions which were mostly seen during the intervention. [Conclusion] The
      BioRescue is a pleasant and interesting treatment method, well suited for
      institutionalized older adults in need of lifelong physical therapy.

PMID- 28744034
TI  - Comparison of the effects of core stabilization and chest mobilization exercises
      on lung function and chest wall expansion in stroke patients.
AB  - [Purpose] The main purpose of this study was to compare the effects of core
      stabilization and chest mobilization exercises on pulmonary function and chest
      expansion in chronic stroke patients. [Subjects and Methods] Thirty stroke
      patients were randomly divided into two groups: a core stabilization exercise
      group (n=15) and a chest mobilization exercise group (n=15). Each exercise was
      performed 3 times per week for 30 minutes for 4 weeks, and pulmonary function and
      chest expansion when breathing were measured for both groups. [Results] There
      were significant increases in both forced vital capacity and forced expiratory
      volume in 1 second before and after intervention. Core stabilization exercise
      resulted in a significant increase in peak expiratory flow, and significant
      increases in upper and lower chest expansion were detected with chest
      mobilization exercise. However, no significant difference was revealed between
      the two groups. [Conclusion] This study suggested that both exercises were
      effective in some aspects of pulmonary function while core stabilization can help
      increase peak expiratory flow and chest mobilization can assist with chest
      expansion.

PMID- 28744035
TI  - Therapeutic efficacy of three hyaluronic acid formulations in young and middle
      aged patients with early-stage meniscal injuries.
AB  - [Purpose] To investigate and compare the efficacy of three hyaluronic acid
      formulations in patients with early-stage meniscal injuries. [Subjects and
      Methods] Male and female patients who were admitted to our clinic between January
      2013 and December 2013, diagnosed with early-stage meniscus lesions of the knee,
      and given a hyaluronic acid treatment were included in this retrospective study.
      Patients were categorized into 3 groups according to their treatments: MONOVISC,
      OSTENIL PLUS, or ORTHOVISC. Scores from a Visual Analog Scale and the Western
      Ontario and McMaster Universities Arthritis Index were evaluated at baseline and
      one, three, and six months after baseline. [Results] A total of 55 patients were
      included in this study. Most of the patients were female (55%), and the mean age
      of the patients was 42.4 (+/- 8.1) years. Based on the pre- and post-injection
      data, there was significant reductions both in the Visual Analog Scale score and
      the Western Ontario and McMaster Universities Arthritis Index score after the
      injections for all groups. According to intergroup comparisons, no significant
      difference was observed in terms of efficacy. [Conclusion] Three hyaluronic acid
      formulations produced a similar efficacy in patients with meniscal injuries, and
      further studies are needed to evaluate long-term results.

PMID- 28744036
TI  - Interrelationship between postural balance and body posture in children and
      adolescents.
AB  - [Purpose] This study examined possible interrelationships between postural sway
      and posture parameters in children and adolescents with a particular focus on
      posture weakness. [Subjects and Methods] 308 healthy children and adolescents
      (124 girls, 184 boys, aged 12.3 +/- 2.5 years) participated in the study. Posture
      parameters (posture index, head protrusion, trunk inclination) were determined
      based on posture photos in the sagittal plane. Postural sway was measured during
      20 seconds on a force plate. The Pearson's product-moment correlation
      coefficients between the anthropometric and posture parameters and the sway path
      length (SPL) were calculated, as well as the coefficient of determination R2.
      [Results] There is a weak but significant correlation between age or body mass
      index of the test subjects and the SPL. There is no statistically significant
      correlation between posture parameters and the SPL. Children and adolescents with
      posture weakness do not exhibit a changed SPL. [Conclusion] Therefore, therapy of
      poor posture must be considered separately from therapeutic measures for the
      improvement of balance skills.

PMID- 28744037
TI  - Effects of Pedalo(r) training on balance and fall risk in stroke patients.
AB  - [Purpose] This study sought to examine the effects of Pedalo(r) training on
      balance and fall risk in stroke patients. [Subjects and Methods] Thirty-one
      subjects with stroke were recruited and randomly allocated into two groups: the
      Pedalo(r) group (n=15) and the Treadmill group (n=16). The Pedalo(r) group
      performed conventional physical therapy program with Pedalo(r) training for 30
      minutes, five times a week, for 8 weeks, while the Treadmill group conducted
      conventional physical therapy programs and treadmill gait training for 30
      minutes, five times a week, for 8 weeks. [Results] After intervention, both
      groups showed a significant improvement in balance. A significant greater balance
      improvement was found in the Pedalo(r) group compared to the Treadmill group.
      Also, a significant reduction in risk of fall was seen in both group but this
      reduction was not significantly different between the two groups. [Conclusion]
      Pedalo(r) training may be used to improve balance and reduce fall risk in stroke
      patients.

PMID- 28744038
TI  - Changes in cardiopulmonary function according to posture during recovery after
      maximal exercise.
AB  - [Purpose] This study was undertaken to measure cardiopulmonary function according
      to body position during the recovery period after maximal exercise and to
      identify an effective position after high-intensity exercise. [Subjects and
      Methods] Fifteen male university students in their twenties participated in the
      study. The subjects were randomly assigned to the supine position, the sitting
      position, or the trunk forward leaning position during the recovery period
      following maximal exercise. Oxygen uptake, minute ventilation volume, respiration
      rate, and heart rate according to posture were measured in a stable state, at
      maximal exercise loading, and at 1, 3, and 5 minutes after maximal exercise.
      [Results] Changes of cardiopulmonary function according to posture during the
      recovery period after maximal exercise showed that minute ventilation volume was
      smaller in the trunk forward leaning position than in the sitting or supine
      positions, and oxygen uptake also declined. [Conclusion] The trunk forward
      leaning position has a more positive effect on pulmonary ventilation after high
      intensity exercise.

PMID- 28744039
TI  - Effectiveness of physical activity as primary preventive care for lower urinary
      tract symptoms in elderly people through the "Muscle Enhancing Club".
AB  - [Purpose] The aim of this study was to examine the relationship between physical
      activity (PA) in elderly people as preventive exercise for lower urinary tract
      symptoms (LUTS) or overactive bladder (OAB), and how PA in primary preventive
      care can impact change upon LUTS. [Subjects and Methods] An interview sheet
      featuring LUTS domains (IPSS/QOL and OABSS questionnaire) was distributed to all
      participants (104 males and 494 females) who attended the public elderly people's
      physical exercise class "Muscle Enhancing Club 2010" in Asahikawa city. [Results]
      The interview sheet was collected from 65 males (75.4 +/- 5.79 years of age) and
      304 females (72.7 +/- 5.23 years of age). In all cases, there was a statistically
      significant difference of QOL. In 77 LUTS cases, there was a statistically
      significant difference in the change of the following LUTS domains: incomplete
      bladder emptying, frequency, nocturia, QOL, urgency, and OABSS total score. In 61
      OAB cases, there was a statistically significant difference in the change of the
      following LUTS domains: QOL, urgency, and OABSS total score. [Conclusion] PA, as
      a preventative exercise for elderly people, led to improvements in LUTS,
      especially storage symptoms and QOL. Our data show that gross movement and
      education was beneficial. From the point of preventive medicine, various exercise
      classes, organized by the local government and others, also indicated that these
      classes increase the possibility of improvement to LUTS.

PMID- 28744040
TI  - An estimation of knee and ankle joint angles during extension phase of standing
      up motion performed using an inertial sensor.
AB  - [Purpose] Motion capture system is difficult to use in daily life. The aim of
      this study was to propose an estimation model for knee and ankle joint angle
      measurements and locate body center of gravity (COG) of the extension phase
      during standing-up motion. [Subjects and Methods] Seven healthy male volunteers
      were enrolled. An estimation model was proposed for the knee and ankle joint
      angle measurements by combining the angle and acceleration of the trunk, based on
      readings from the inertial sensor attachment on the subject's chest, during the
      extension phase. Joint angles and COG position were compared to those obtained by
      a motion capture system. [Results] The joint angles and COG position demonstrated
      high correlation coefficients which represent strong correlation between the
      proposed model and the motion capture system. The proposed model could estimate
      the joint angle during extension phase, with a maximum error of 4.58 degrees, as
      well as COG position in the horizontal and vertical directions with maximum
      errors of 4.48 cm and 3.19 cm, respectively. [Conclusion] The proposed system
      could be used instead of motion capture system to estimate knee and ankle joint
      angles; however, the estimation of the COG position was insufficient because of
      lacked accuracy.

PMID- 28744041
TI  - The relationship between physical function in the elderly and judgment error in
      walking speed.
AB  - [Purpose] "Judgment error," defined as a difference between the actual and the
      imagined performance, is often observed in elderly persons. The aims of this
      study were to assess subjective judgment errors in elderly persons, and to
      evaluate the relationship between physical function and judgment error in walking
      speed. [Subjects and Methods] A total of 106 community-dwelling elderly
      individuals participated. Subjects observed video footage of a model walking an
      obstacle course, and were asked to subjectively compare the model's gait speed
      with their own gait speed. When the subjective comparison differed from the
      actual difference, it was considered as a judgment error. Physical function was
      compared between those with and without judgment error. [Results] Significant
      interaction effects between the actual performance and subjective perception were
      found for the walking time on the obstacle course and the Activities-specific
      Balance Confidence Scale score (utilized as an index of self-confidence in own
      balance ability and a fear of falling). [Conclusion] The results demonstrate that
      some elderly persons tend to overestimate their balance and ambulation function
      compared to another person, even though they had low physical function and low
      self-confidence in terms of balance. These elderly individuals might have a high
      risk of accidents.

PMID- 28744042
TI  - Lower-limb muscle strength according to bodyweight and muscle mass among middle
      age patients with type 2 diabetes without diabetic neuropathy.
AB  - [Purpose] This study assessed the effects of type 2 diabetes without diabetic
      polyneuropathy on muscle strength according to body composition in middle age
      patients. [Subjects and Methods] This study included 45 non-diabetic individuals
      (control group) and 50 patients with type 2 diabetes (DM group), 40 to 64 years
      of age. The body composition was examined, including the leg muscle volume (LMV),
      which was the sum of the lower-limb muscle mass. The muscle strength was also
      examined, and the knee extension force (KEF), ankle dorsiflexion force (ADF). The
      KEF and ADF were normalized to the bodyweight, and the total leg muscle force
      (TLMF) were calculated by combining the KEF and ADF. The leg muscle quality (LMQ)
      was calculated as the TLMF normalized with the LMV. [Results] While no
      significant differences were found in the LMV between groups, the body mass index
      were higher in the DM group than in the control group. Significant differences
      were observed in %KEF, %ADF, and the LMQ in the DM group, with 15.8%, 18.7%, and
      11.5% lower values than those in the control group, respectively. [Conclusion]
      The results of this study may demonstrate that muscle weakness occurs before
      diabetes progresses to a severe condition.

PMID- 28744043
TI  - Comparison of temporal changes in trunk flexion angle and gluteal pressure during
      continuous sitting.
AB  - [Purpose] This study investigated temporal changes in trunk flexion angle and
      gluteal pressure during computer work with continuous sitting. [Subjects and
      Methods] This study involved 10 males subjects aged 21-29 years. During 30 min of
      data collection with a Tekscan system and a video camera, peak gluteal pressure
      and changes in trunk flexion angle were analyzed with the COMFOM at research 6.20
      and Pro-Trainer 10.1 programs, respectively, at 10, 20, and 30 min. [Results] The
      result showed no significant change in gluteal pressure after 10, 20, or 30 min.
      However, changes in trunk flexion angle increased significantly after 10 min <20
      min <30 min. [Conclusion] Trunk flexion is necessary for repositioning, unless
      one can maintain a posture for a long time without movement. Future research
      should analyze repositioning methods according to individual characteristics.

PMID- 28744044
TI  - The effects of occupation-centered activity program on fall-related factors and
      quality of life in patients with dementia.
AB  - [Purpose] The purpose of this study was to investigate the effects of an
      occupation-centered activity program for dementia patients living in a local
      community, and examined the effects of the occupation-centered activity program
      on their cognitive functions, fall-related factors, and quality of life.
      [Subjects and Methods] Thirty subjects were divided into two groups: the
      experiment group (n=15) and the control group (n=15). The occupation-centered
      activity program was then applied to dementia patients for 60 minutes, 5
      times/week for 12 weeks. To identify their cognitive functions before and after
      the intervention occupation-centered activity program, Mini-Mental State
      Examination-Korea (MMSE-K) and the Global Deterioration Scale (GDS) were used. To
      assess fall-related factors, Korean Falls Efficacy Scale for the Elderly (FES-K)
      was used and leg strength, agility, and balance of the participants was measured.
      To examine quality of life, the Korean version of Quality of Life-Alzheimer's
      Disease Scale (KQOL-AD) was used. [Results] The results of the intervention
      showed that although cognitive function improved in both the experimental and
      control groups, fall-related factors and the quality of life significantly
      improved only in the experimental group. [Conclusion] This indicates that the
      occupation-centered activity program had a positive effect on dementia patients'
      cognitive functions, fall-related factors, and quality of life.

PMID- 28744045
TI  - Effects of joint immobilization and hindlimb unloading on collagen fibers of
      soleus muscles in rats.
AB  - [Purpose] The purpose of this study was to determine whether collagen fibers
      cause a difference in a contracture resulting from a combination of joint
      fixation and hindlimb unloading as compared to joint fixation only. [Subjects and
      Methods] The subjects of this study were 21 female Wistar rats divided into 4
      groups as follows: Control Group (CON, n=7); Joint Fixation Group (JF, n=7),
      Hindlimb Unloading Group (HU, n=7), Joint Fixation Plus Hindlimb Unloading Group
      (JF+HU, n=7). This study was conducted for 1-week. Ankle joint range of motion
      and positive areas of collagen using fluorescent stain were analyzed. [Results]
      Ankle joint range of motion in JF + HU showed an increase compared to that of JF.
      Positive areas of Type I collagen in JF+HU showed an increase as compared with
      that of JF. [Conclusion] The results of this study suggested that the difference
      in a contracture caused by only joint immobilization and by a combination of
      joint immobilization and hindlimb unloading were significantly associated with
      Type I collagen.

PMID- 28744046
TI  - Effects of an abdominal muscle exercise program in people with intellectual
      disabilities residing in a residential care facility.
AB  - [Purpose] The purpose of this study was to provide basic information as reference
      and guidelines for the implementation of abdominal muscle exercise programs for
      people with intellectual disabilities residing in residential care facilities.
      [Subjects and Methods] The study period was 12 weeks, from July 1, 2015, to
      September 30, 2015. The study participants comprised of 10 people with
      intellectual disabilities who were residing in a residential care facility. An
      occupational therapist measured each subject's weight and physical fitness
      (muscle strength and flexibility). Collected data were encoded by using items and
      analyzed using SPSS ver.18.0. [Results] Weight decreased significantly, and
      physical fitness (muscle strength and flexibility) increased significantly.
      [Conclusion] To actively improve abdominal muscle strength and health management
      in people with intellectual disabilities residing in residential care facilities,
      consistent implementation of abdominal muscle exercise programs and improvements
      are indispensable, as these could lead to the development of systematic programs
      for rehabilitation physical activities.

PMID- 28744047
TI  - Effects of lingual strength training on lingual strength and articulator function
      in stroke patients with dysarthria.
AB  - [Purpose] This study investigated the effects of lingual strength training (LST)
      on lingual strength and articulator function in stroke patients with dysarthria.
      [Subjects and Methods] 16 stroke patients with dysarthria were randomly assigned
      into two groups: the experimental group (n=8) or the control group (n=8). Both
      groups received the conventional rehabilitation therapy at 30 min/day, 5 times
      for week, and during 4 weeks, and the experimental group received an additional
      30 min of LST using the Iowa Oral Performance Instrument (IOPI). The Maximum
      Isometric Tongue Pressures (MIPs) was used to assess the lingual strength and the
      Alternating-Motion Rate (AMR) and Sequential-Motion Rate (SMR) were used to
      measure the articulator function. [Results] After the intervention, the
      experimental group showed a significant improvement in MIPs and AMR (/te/) than
      the control group. [Conclusion] Findings of this study suggest that LST provides
      positive effects on lingual strength and articulator function, and thus can be
      used as an interventional method in stroke patients with dysarthria.

PMID- 28744048
TI  - Effects of kinesio taping to the quadriceps femoris muscles on functions of
      elderly women.
AB  - [Purpose] The purpose of this study is to investigate effects of kinesio taping
      to the quadriceps femoris on functions of elderly women. [Subjects and Methods]
      The subjects of this study were 22 elderly women with osteoarthritis, who were
      divided into two groups of a general exercise group 12 elderly and a kinesiology
      taping group 12 elderly. Two groups underwent a 30-min exercise for strengthening
      the lower limb muscles three times per week for four weeks. After the exercise,
      the kinesiology taping group was treated by the kinesio taping. Kinesio tapes
      were attached to the quadriceps femoris, three times per week for four weeks. The
      Korean Western Ontario and McMaster Universities Osteoarthritis Index, sit to
      standing, and Time up & Go test were used for assessment before and after the
      intervention. [Results] As a result, the kinesiology taping group showed
      significant differences in the Korean Western Ontario and McMaster Universities
      Osteoarthritis Index, sit to standing, and Time up & Go test between pre- and
      post-intervention, while the general exercise group showed no significant
      differences in pre- and post-intervention. There was a significant difference in
      between-group comparison. [Conclusion] The kinesio taping for the quadriceps
      femoris was effective on improving functions of elderly women with
      osteoarthritis.

PMID- 28744049
TI  - The effects of task-oriented training with altered sensory input on balance in
      patients with chronic stroke.
AB  - [Purpose] The purpose of this study was to identify the effects of task-oriented
      training with altered somatosensory input on the balance ability of chronic
      stroke patients. [Subjects and Methods] Twenty-six subjects with chronic stroke
      were divided into an experimental group (n=14) and a control group (n=12). Both
      groups attended physical therapy sessions five times a week for four weeks. The
      experimental group performed additional, task-oriented training with altered
      sensory input three times a week for four weeks. Limit-of-stability tests were
      conducted before and after the intervention. In addition, all subjects were
      evaluated using the Berg Balance Scale (BBS) and Korean Activities-Specific
      Balance Confidence Scale before and after the intervention. [Results] There was a
      significant interaction between time and group on BBS scores, on the total
      surface area of the limit of stability, and on the surface area of the limit of
      stability of the affected side. However, an analysis of covariance in which the
      baseline values of each variable served as the covariates showed that only the
      post-intervention BBS score of the experimental group was significantly higher
      than that of the control group. [Conclusion] Task-oriented training with altered
      somatosensory input can improve functional balance in patients with chronic
      stroke.

PMID- 28744050
TI  - Effect of standing postural deviations on trunk and hip muscle activity.
AB  - [Purpose] It is very important to consider effects that postural deviations has
      on muscle activity when treating low back pain. Therefore, activities of trunk
      and hip joint muscles in healthy adults while they attempted three postural
      conditions of neutral, sway-back, and lordosis was compared and evaluated in this
      study. [Subjects and Methods] The subjects comprised 17 healthy adult male
      volunteers. The muscle activity and spinal curve were measured while the subjects
      attempted different postural conditions (neutral, sway-back, and lordosis) as
      defined in the text. [Results] Activity of trunk and hip inner muscles was
      decreased in sway-back posture, and only activity of the trunk back muscles was
      increased in lordosis. [Conclusion] This results were suggested that postural
      deviations affected muscle control in the lumbo-pelvic area.

PMID- 28744051
TI  - Effects of endurance exercise and half-bath on body composition,
      cardiorespiratory system, and arterial pulse wave velocity in men with
      intellectual disabilities.
AB  - [Purpose] The purpose of this study was to investigate the effects of endurance
      exercise and half-bath on body composition, cardiorespiratory system, and
      arterial pulse wave velocity of men with intellectual disabilities. [Subjects and
      Methods] Twenty-four men with intellectual disabilities, but capable of learning,
      were randomly assigned to aerobic exercise (N=8), half-bath (N=8), or control
      (N=8) treatment groups. Over the 12-week treatment period, the aerobic exercise
      group did treadmill and stationary bicycle. The half-bath treatment group was
      placed in a sitting position in a 39-40 degrees C bath for 10 minutes. [Results]
      The aerobic exercise group showed a significant decrease in body fat than those
      in the half-bath and control groups. In addition, there was an increase in the
      respiratory system of the aerobic exercise group but no increase in the half-bath
      and control groups. The arterial pulse wave velocity change was greatest in the
      aerobic exercise group, but the half-bath group also showed a velocity change
      from that in the control group. [Conclusion] Aerobic exercise and a half-bath can
      have positive effects on improving body composition, respiratory system, and
      vascular function of people with intellectual disabilities.

PMID- 28744052
TI  - Ultrasonography of the shoulder: asymptomatic findings from working-age women in
      the general population.
AB  - [Purpose] The aim of this study was to estimate the prevalence of abnormal
      shoulder ultrasonographic findings in a sample of asymptomatic women. [Subjects
      and Methods] A secondary analysis of a cross-sectional study was performed. We
      recruited 305 women (aged 18-56 years). All the subjects had a structured
      interview screening for self-reported symptoms and underwent a shoulder
      ultrasonographic examination, in which both shoulders were examined. The
      radiologist was blinded to the clinical history of the participants. All
      detectable shoulder abnormalities were collected. [Results] Of the subjects, 228
      (74.75%) were asymptomatic at both shoulders, and 456 asymptomatic shoulders were
      analyzed. Lack of uniformity (supraspinatus, infraspinatus, subscapularis, and
      biceps brachii long head) was found in 28 shoulders (6.14%), 19 (4.17%) on the
      dominant side and 9 (1.97%) on the non-dominant side. Tendinosis (supraspinatus,
      infraspinatus, subscapularis, and biceps brachii long head) was found in 19
      shoulders (5.32%), 12 (2.63%) on the dominant side and 7 (1.53%) on the non
      dominant side. Calcification and other abnormal findings were reported.
      [Conclusion] The most common abnormalities were calcifications within the rotator
      cuff tendons and humeral head geodes; other degenerative findings were less
      common.

PMID- 28744053
TI  - The effect of motor imagery training for trunk movements on trunk muscle control
      and proprioception in stroke patients.
AB  - [Purpose] The present study was conducted to evaluate the effect of motor imagery
      training for trunk movements on trunk muscle control and proprioception in stroke
      patients. [Subjects and Methods] A total of 12 study subjects were randomly
      assigned to the experimental group (a motor imagery training group) and the
      control group (a neurodevelopmental treatment, NDT) group. The two groups were
      treated five times (30 minutes each time) per week for 4 weeks. The experimental
      group underwent imagery training for 10 minutes and trunk control centered NDT
      for 20 minutes and the control group underwent only trunk control centered NDT
      for 30 minutes. The trunk muscle activity and the position sense of the subjects
      were evaluated before and after the intervention. [Results] The two groups showed
      significant improvements in muscle activity after the intervention. Only the
      experimental group showed significant improvements in proprioception. The
      experimental group showed significant improvements in the variations of muscle
      activity and proprioception compared to the control group. [Conclusion] Motor
      imagery training for trunk movements can be effectively used to improve trunk
      muscle activity and proprioception in stroke patients.

PMID- 28744054
TI  - The effects of progressive neuromuscular training on postural balance and
      functionality in elderly patients with knee osteoarthritis: a pilot study.
AB  - [Purpose] To determine the effects of progressive neuromuscular training on
      postural balance and functionality in elderly patients with knee osteoarthritis
      (OA). [Subjects and Methods] Eleven participants between 60 and 75 years of age
      performed the progressive neuromuscular training for 8 weeks and 4 weeks of
      follow-up. The area and velocity of the center of pressure were measured on a
      force platform, and the functionality was measured with a Western Ontario and
      McMaster Universities Osteoarthritis Index. [Results] The area and velocity
      (anteroposterior and mediolateral directions) of the center of pressure showed
      significant differences after 4 and 8 weeks of intervention. Additionally, the
      global score and some questionnaire dimensions (pain and physical function)
      showed significant differences after 4 and 8 weeks of intervention. These changes
      were maintained in all variables at week 4 of follow-up. [Conclusion] The
      intervention generated improvements in balance and functionality in elderly
      patients with knee OA. These changes were observed after 4 weeks of training and
      were maintained 4 weeks after the end of the intervention.

PMID- 28744055
TI  - The influence of trait anxiety and illusory kinesthesia on pain threshold.
AB  - [Purpose] It has also been reported that decreased activity in the reward pathway
      causes a decrease in brain activity in the descending pain control system in
      people with high trait anxiety. Activation of this system is dependent on both
      the reward pathway and motor areas. Recently, studies have also shown that motor
      areas are activated by illusory kinesthesia. It was aimed to explore whether
      anxiety trait modulates the influence of illusory kinesthesia on pain threshold.
      [Subjects and Methods] The pain threshold and trait anxiety at rest before
      vibratory tendon stimulation (the task) were measured. After the task, the pain
      threshold, the illusory kinesthesia angle, and the intensity of illusory
      kinesthesia for patients with and without illusory kinesthesia were measured. A
      total of 35 healthy right-handed students participated, among whom 22 and 13 were
      included in the illusion and no-illusion groups, respectively. [Results] There
      was a significant increase in the pain threshold after task completion in both
      groups; however, there was no statistically significant difference between the
      two groups. Correlational analysis revealed that State-Trait Anxiety Inventory
      trait score correlated negatively with the pain threshold in the no-illusion
      group, but there was no correlation in the illusion group. [Conclusion] The pain
      threshold improved regardless of the size of trait anxiety in the illusion group,
      but did not improve merely through sensory input by vibratory stimulation in the
      no-illusion group. Thus, illusory kinesthesia has effect of increasing the pain
      threshold.

PMID- 28744056
TI  - Comparison of muscle synergies before and after 10 minutes of running.
AB  - [Purpose] The purpose of this study was to investigate the modular control of
      locomotor tasks and compared the modules before and after a running intervention.
      [Subjects and Methods] Electromyographic measurements were performed on eight
      young, healthy males engaged in a 60s run on a treadmill at 2.8 m/s before and
      immediately after the 600s of running intervention. Electromyographic data for 15
      trunk and lower-limb muscles on the right side were recorded. Muscle synergies
      were extracted from the electromyography signals using non-negative matrix
      factorization. [Results] Four modules explained the electromyographic activity of
      all muscles and had the functions of load acceptance (module 1), push-off (module
      2), preparation of landing (module 3), and trunk-stabilization activity during
      the stance phase (module 4). Modules 1, 2, and 3 matched the basic modules
      reported in previous studies; whereas, module 4 was different before and after
      the intervention. [Conclusion] Before the intervention, module 4 engaged the
      trunk muscles and it was activated in the stance phase during running. However,
      after the intervention, module 4 engaged the muscles around the pelvis and it was
      activated after landing. This result suggests that the posture control changes
      from the trunk muscles to the lower-limb muscles after 10 minutes running.

PMID- 28744057
TI  - The effects of treatment room lighting color on time perception and emotion.
AB  - [Purpose] The purpose of this study was to investigate the perceived treatment
      times and emotional reactions under different light colors in the treatment room.
      [Subjects and Methods] Subjects in this study were 20 healthy young students in
      their 20s. Under each lighting condition (blue, red, white, and yellow)
      differentiated by color, each subject laid on a therapeutic bed and underwent
      ultrasound therapy. Subjects were instructed to press a stopwatch every 1 minute,
      for a total of 5 times, after therapy started according to their perception of
      time while the stopwatch's time indicator was blocked. After the experiments,
      self-administered questionnaires were given to subjects to measure their
      emotional reactions. [Results] In terms of K-POMS scores, the mood states of
      depression-dejection, anger-hostility, and confusion-bewilderment were higher
      scores for blue and red lights compared to yellow light. The mood state of vigor
      activity were higher scores for yellow and white lights compared to blue and red
      lights. [Conclusion] Therefore, it is important to take necessary measures to
      prevent the negative effects that blue and red light-based therapy can have on
      patient mood.

PMID- 28744058
TI  - The reliability and validity of the Korean version of the Japanese orthopaedic
      association back pain evaluation questionnaire.
AB  - [Purpose] The purpose of this study was to establish the reliability and validity
      of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire
      (JOABPEQ) translated into Korean for use with patients' low back pain. [Subjects
      and Methods] Sixty-two subjects with low back pain, 28 men and 34 women,
      participated in the study. Reliability was determined by using the intra class
      correlation coefficient and Cronbach's alpha for internal consistency. Validity
      was examined by correlating the JOABPEQ scores with the 36 item short form health
      survey (SF 36). [Results] Test-retest reliability was 0.75-0.83. The criterion
      related validity was established by comparison with the Korean version of the SF
      36. [Conclusion] The Korean version of the JOABPEQ was shown to be a reliable and
      valid instrument for assessing low back pain.

PMID- 28744059
TI  - Effect of yoga practices on micronutrient absorption in urban residential school
      children.
AB  - [Purpose] This study was conducted with a view to find out the effect of yoga
      practices on micronutrient absorption in urban residential school children.
      [Subjects and Methods] The study population comprised 66 urban school children
      aged 11-15 years staying in a residential school in Pune City, Maharashtra,
      India. A stratified random sampling method was used to divide the students into
      experimental and control groups. There were 33 students in experimental group and
      33 students in control group. Both experimental and control groups were assessed
      for the status of zinc, copper, iron and magnesium at the baseline and at the end
      of 12 weeks of yoga training. The study participants of experimental group
      underwent yoga training for 12 weeks, for one hour in the morning for six days a
      week. The control group did not undergo any yoga training during this time
      period. [Results] The experimental group participants showed significant
      improvement in micronutrient absorption as compared to control group.
      [Conclusion] The findings of this study indicate that yoga practices could
      improve micronutrient absorption in urban residential school children.

PMID- 28744060
TI  - Effects of physiotherapy treatment for urinary incontinence in patient with
      multiple sclerosis.
AB  - [Purpose] The aim of the study was to evaluate the benefits of physical therapy
      for urinary incontinence in patients with multiple sclerosis and to verify the
      impact of urinary incontinence on the patient's quality of life. [Subject and
      Methods] A case study of a 55-year-old female patient diagnosed with multiple
      sclerosis and mixed urinary incontinence was conducted. Physical therapy sessions
      were conducted once a week, in total 15 sessions, making use of targeted
      functional electrical vaginal stimulation, along with active exercises for the
      pelvic floor muscles and electrical stimulation of the posterior tibial nerve,
      behavioral rehabilitation and exercise at home. [Results] After 15 physical
      therapy sessions, a patient diagnosed with multiple sclerosis and mixed urinary
      incontinence showed continued satisfactory results after five months. She showed
      better quality of life, higher strength of pelvic floor muscle and reduced
      urinary frequency without nocturia and enuresis. [Conclusion] The physical
      therapy protocol in this patient with multiple sclerosis and mixed urinary
      incontinence showed satisfactory results reducing urinary incontinence
      symptomatology and improving the patient's quality of life.

PMID- 28744061
TI  - Reversing thoracic hyperkyphosis: a case report featuring mirror image(r)
      thoracic extension rehabilitation.
AB  - [Purpose] To present a case of non-surgical reduction of thoracic hyperkyphosis
      utilizing a multimodal rehabilitation program emphasizing the mirror image(r)
      concept. [Subject and Methods] A 15-year-old female presented to a rehabilitation
      office suffering from back and neck pains and headaches. The patient was treated
      sporadically over a period of 13-months. Treatment consisted of anterior thoracic
      translation and thoracic extension exercises, spinal traction and spinal
      manipulation. [Results] After 13-months of treatment the patient displayed a
      significant reduction in hyperkyphosis and a dramatic correction of her overall
      posture and spine alignment corresponding to the reduction in back/neck pains,
      headaches and the simultaneous improvement of various other health issues.
      [Conclusion] Thoracic hyperkyphosis can be reduced through a multimodal
      rehabilitation program emphasizing mirror image thoracic extension procedures.

PMID- 28744062
TI  - Effects of aquatic walking exercise using a walker in a chronic stroke patient.
AB  - [Purpose] The aim of this study was to examine the usefulness of aquatic walking
      exercise using a walker for chronic stroke patients. We also examined the
      psychological effects on the study subject and the primary caregiver before and
      after aquatic walking exercise. [Subject and Methods] The subject was a 60-year
      old male with bilateral paralysis after a cerebrovascular accident. The Fugl
      Meyer Assessment (FMA) total score was 116 on the right and 115 on the left. The
      intervention combined aquatic and land walking exercise. A U-shaped walker was
      used for both water and land exercise. Continuous walking distance was the
      measure used to evaluate land walking ability. The psychological effects on the
      study subject and the primary caregiver were examined with the questionnaire.
      [Results] In aquatic walking, the mean time to walk 5 m showed an increase from
      the intervention after two months. After the aquatic walking and land walking
      combination, continuous walking distance also showed a prolonged trend. In the
      survey given to the main caregivers, improvements were observed. [Conclusion]
      Aquatic walking practice using a walker improved motivation in a chronic stroke
      patient, leading to improved walking ability, with a positive psychological
      influence on the participant and family caregiver.

PMID- 28744063
TI  - The effects of bandaging with an additional pad and taping on secondary arm
      lymphedema in a patient after mastectomy.
AB  - [Purpose] The purpose of this case study was to determine the effectiveness of
      bandaging the arm of a patient with secondary lymphedema on the patient's quality
      of life, arm volume and arm function using an additional pad and taping along
      with some other standard therapy modalities for lymphedema. [Subjects and
      Methods] I used a bandage with an additional pad and taping, along with MLD,
      exercise, and skin care to treat a patient with unilateral breast-cancer-related
      arm lymphedema who had fibrotic tissue on her lower arm and hand. I made a pad
      called a "muff" and applied it under tape while using Vodder's technique.
      Treatment was performed during 5 therapy sessions a week for 2 weeks. [Results]
      After the physiotherapy sessions, the excess edema volume decreased to 608 ml,
      and the percentage of excess volume (PEV) was 9.6%. The therapeutic efficacy,
      measured as percentage reduction of excess volume (PREV), was -79.5%, meaning
      that the edema volume was reduced 79.5%. The use of an additional pad and taping
      on a large edematous site with fibrotic changes can produce more efficacious
      lymphedema care. [Conclusion] The use of an additional pad and taping on a large
      edematous site with fibrotic changes has demonstrated a positive result in
      lymphedema management for a post mastectomy patient and, therefore, further
      studies on this method are suggested with a larger sample size.

PMID- 28744064
TI  - Effects of central and unilateral posteroanterior mobilization on cervical
      lordosis, muscle stiffness and ROM in patient with ankylosing spondylitis: case
      study.
AB  - [Purpose] The aim of this study was to determine the effects of central and
      unilateral posteroanterior (PA) mobilization on cervical lordosis, muscle
      stiffness and range of motion in a patient with ankylosing spondylitis (AS).
      [Subject and Methods] The subject of this case study was diagnosed with AS in
      1997. At baseline, variance was measured without any intervention during the
      first 3 days (2016.6.13-2016.6.15). Cervical PA mobilization was applied to each
      segment from C2-C7 from the 4th to the 11th day for 8 days. Intervention was not
      performed from the 12th to the 15th days for 4 days. Variances were measured a
      final time without intervention on the 16th day (2016.6.28). [Results] Cervical
      lordosis was seen to have increased. Muscle stiffness was significantly decreased
      after intervention and the effect of treatment lasted for five days without any
      additional intervention. The cervical flexion and extension angles were
      increased. However these increases were not statistically significant. Both the
      lateral flexion and left rotation angle were significantly increased and the
      effects of treatment lasted for five days without any additional intervention.
      [Conclusion] These results suggest that central and unilateral PA mobilization is
      effective in increasing cervical lordosis and range of motion, and decreasing
      muscle stiffness in patients with AS.

PMID- 28744065
TI  - Effect of modified leg-raising exercise on the pain and pelvic angle of a patient
      with back pain and excessive lordosis.
AB  - [Purpose] This study developed a modified active leg-raising exercise to decrease
      lumbar lordosis and assessed its effectiveness in a patient with low back pain
      and excessive lumbar lordosis. [Subject and Methods] The subject was a 56-year
      old woman with excessive lordosis, who complained of continuous severe LBP pain
      at the L5 level for 1 year. The subject performed the modified active leg-raising
      exercise while flexing the neck. She performed the modified active leg-raising
      exercises for 2 weeks, performing three sets of 30 repetitions per day. [Results]
      The patient's anterior pelvic tilt angle decreased from 20 degrees  and 23
      degrees  to 16 degrees  and 17 degrees  on the right and left sides,
      respectively. In backward trunk extension, the VAS score of her back pain
      decreased to 4 (from the initial score 8). [Conclusion] This result suggests that
      the modified leg-raising combined with neck flexion helped to recovery the pelvic
      posture and back pain. The subject could also easily fix her pelvis and avoid
      moving her lower trunk while exercising.

PMID- 28744066
TI  - Effects of Robot-Assisted Training for the Unaffected Arm in Patients with
      Hemiparetic Cerebral Palsy: A Proof-of-Concept Pilot Study.
AB  - On a voluntary basis, 10 adolescents with hemiparesis due to cerebral palsy and
      11 neurologically healthy control subjects participated in this proof-of-concept
      pilot study. The aim was to examine the effects of robot-assisted training for
      the unaffected arm in patients with hemiparetic cerebral palsy. Baseline
      comparison between the unaffected arm of the hemiparetic patients with cerebral
      palsy and the dominant arm of healthy control subjects showed significant
      differences on the Jebsen-Taylor Hand Function test and action planning ability
      tests. Within-group comparison after ten 30-minute sessions (five days a week for
      two consecutive weeks) of robot-assisted training for the unaffected arm showed
      significant improvements in patients with cerebral palsy on the Jebsen-Taylor
      Hand Function test (performed at both hands) and action planning ability test
      (evaluated at the unaffected arm). Our findings are in line with previous
      evidences of action planning deficits at the unaffected arm in patients with
      hemiparetic cerebral palsy and support the hypothesis that robot-assisted
      training for the unaffected arm may be useful to improve manual dexterity and
      action planning in patients with hemiparesis due to cerebral palsy.

PMID- 28744068
TI  - Subtle versus the obvious - "Is it time for the Smart Radiologist?"

PMID- 28744067
TI  - Helminth Products Potently Modulate Experimental Autoimmune Encephalomyelitis by
      Downregulating Neuroinflammation and Promoting a Suppressive Microenvironment.
AB  - A negative correlation between the geographical distribution of autoimmune
      diseases and helminth infections has been largely associated in the last few
      years with a possible role for such type of parasites in the regulation of
      inflammatory diseases, suggesting new pathways for drug development. However, few
      helminth-derived immunomodulators have been tested in experimental autoimmune
      encephalomyelitis (EAE), an animal model of the human disease multiple sclerosis
      (MS). The immunomodulatory activities of Taenia crassiceps excreted/secreted
      products (TcES) that may suppress EAE development were sought for. Interestingly,
      it was discovered that TcES was able to suppress EAE development with more
      potency than dexamethasone; moreover, TcES treatment was still effective even
      when inoculated at later stages after the onset of EAE. Importantly, the TcES
      treatment was able to induce a range of Th2-type cytokines, while suppressing Th1
      and Th17 responses. Both the polyclonal and the antigen-specific proliferative
      responses of lymphocytes were also inhibited in EAE-ill mice receiving TcES in
      association with a potent recruitment of suppressor cell populations. Peritoneal
      inoculation of TcES was able to direct the normal inflammatory cell traffic to
      the site of injection, thus modulating CNS infiltration, which may work along
      with Th2 immune polarization and lymphocyte activation impairment to downregulate
      EAE development.

PMID- 28744069
TI  - Alteration in the number and integrity of white matter tracts in the preterm: A
      quantitative diffusion tensor imaging and diffusion fibre tractography in
      children.
AB  - PURPOSE: Periventricular white matter is most commonly injured in preterm babies
      with hypoxia. To assess white matter damage, we decided to perform diffusion
      tensor imaging (DTI) in preterm children with history of hypoxia and magnetic
      resonance imaging (MRI) features of periventricular leukomalacia (PVL) (PTH). We
      hypothesized that the PTH have reduced number of white matter fibres compared to
      age matched pre term children without hypoxia (PTHO), and also depending on the
      severity of PVL, there could be reduction in the number of fibres as well.
      MATERIALS AND METHODS: The present study was carried out at the Government
      Medical College, Thiruvananthapuram. DTI was performed on 15 PTH and 15 PTHO. We
      measured number of fibres and fractional anisotropy of corpus callosum (CC) and
      optic radiations (OR). RESULTS: There was significant difference between two
      groups with regard OR (P < 0.001). The mean number of OR fibres in cases and
      control was 104 +/- 28.44 (mean +/- SD) and 578 +/- 286 (mean +/- SD),
      respectively. The mean number of CC in cases was 953 +/- 429 and in controls was
      1625 +/- 116 with a P value <0.56. No significant difference in FA was seen
      between cases and controls (P = 0.94). CONCLUSIONS: Preterm children with history
      of hypoxia and MRI features of PVL show reduced number of CC and OR compared to
      preterm children without hypoxia. There was significant correlation between PVL
      severity and number of OR fibres which could be due to the preferential
      involvement of periventricular white matter, in which OR has a major
      contribution.

PMID- 28744070
TI  - MRI features in dengue encephalitis: A case series in South Indian tertiary care
      hospital.
AB  - Dengue virus, a RNA virus of family Flaviviradae is considered non-neurotropic.
      Increasing studies and case reports reveal neurological manifestations of dengue
      virus. In our case series, we have evaluated magnetic resonance imaging (MRI)
      findings of 3 patients with dengue fever diagnosed by positive dengue NS1 antigen
      with neurological symptoms, which revealed nonspecific imaging features of dengue
      encephalitis in two cases and dengue meningoencephalitis in one case. Autopsy
      findings are also correlated in 2 patients who succumbed to their disease. This
      case series underlines the consideration of dengue encephalitis in patients of
      dengue fever with neurological symptoms and relevant imaging findings.

PMID- 28744071
TI  - Sequential MR imaging (with diffusion-weighted imaging) changes in metronidazole
      induced encephalopathy.
AB  - Metronidazole-induced neuro-toxicity, though rare, is known. A characteristic
      spatial distribution of lesions in cerebellar dentate nuclei and dorsal pons is
      known. However, temporal progression of lesions on magnetic resonance imaging
      (MRI) has not been described previously. We describe two such cases which
      presented initially with splenial hyperintesity and showed progression to
      characterstic lesions. Both cases improved with stoppage of metronidazole.

PMID- 28744072
TI  - Multimodality imaging spectrum of complications of horseshoe kidney.
AB  - Horseshoe kidney is the most common congenital renal fusion anomaly with an
      incidence of 1 in 400-600 individuals. The most common type is fusion at the
      lower poles seen in greater than 90% of the cases, with the rest depicting fusion
      at the upper poles, resulting in an inverted horseshoe kidney. Embryologically,
      there are two theories hypothesizing the genesis of horseshoe kidney - mechanical
      fusion theory and teratogenic event theory. As an entity, horseshoe kidney is an
      association of two anatomic anomalies, namely, ectopia and malrotation. It is
      also associated with other anomalies including vascular, calyceal, and ureteral
      anomalies. Horseshoe kidney is prone to a number of complications due to its
      abnormal position as well as due to associated vascular and ureteral anomalies.
      Complications associated with horseshoe kidney include pelviureteric junction
      obstruction, renal stones, infection, tumors, and trauma. It can also be
      associated with abnormalities of cardiovascular, central nervous, musculoskeletal
      and genitourinary systems, as well as chromosomal abnormalities. Conventional
      imaging modalities (plain films, intravenous urogram) as well as advanced cross
      sectional imaging modalities (ultrasound, computed tomography, and magnetic
      resonance imaging) play an important role in the evaluation of horseshoe kidney.
      This article briefly describes the embryology and anatomy of the horseshoe
      kidney, enumerates appropriate imaging modalities used for its evaluation, and
      reviews cross-sectional imaging features of associated complications.

PMID- 28744073
TI  - Gadolinium based contrast agents in current practice: Risks of accumulation and
      toxicity in patients with normal renal function.
AB  - Despite being decked as the most prized compounds in the nugget box of contrast
      agents for clinical radiologists, and carrying an indisputable tag of safety of
      the US Food and Drug Administration for close to three decades, all may not be
      seemingly well with the family of gadolinium compounds. If the first signs of
      violations of primum non nocere in relation to gadolinium-based contrast agents
      (GBCAs) appeared in the millennium year with the first published report of skin
      fibrosis in patients with compromised renal function, the causal relationship
      between the development of nephrogenic systemic fibrosis (NSF) and GBCAs, first
      proposed by two European groups in 2006, further precluded their use in
      renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of
      GBCAs, however, has come under hawk-eyed scrutiny with recent reports that
      gadolinium tends to deposit cumulatively in the brain of patients with normal
      hepatobiliary function and intact blood-brain barrier. While the jury on the long
      term hazard significance of this critical scientific finding is still out, the
      use of GBCAs must be guided by due clinical diligence, avoidance of repeated
      doses, and preferring GBCAs with the best safety profiles.

PMID- 28744074
TI  - Multimodality imaging of vaginal rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is a malignant mesenchymal tumor arising from the
      embryonal muscle cells (rhabdomyoblasts), and is the most common soft tissue
      sarcoma in children and young adults accounting for 4-6% of all malignancies in
      this age group. Though rare overall, embryonal rhabdomyosarcoma is the most
      common malignancy arising in the pediatric female genitourinary tract with
      sarcoma botryoides being the most common variant of the tumor. In young and
      adolescent individuals, the cervix and uterus are affected; whereas in infants,
      vaginal lesions are more common. Imaging plays a crucial role not only in the
      initial diagnosis but also in long-term follow-up of genital RMS. We describe a
      rare case of embryonal rhabdomyosarcoma of the vagina occurring in a 23-year-old
      female who presented with abnormal vaginal bleeding ever since she was a child.

PMID- 28744075
TI  - Severity assessment of acute pancreatitis using CT severity index and modified CT
      severity index: Correlation with clinical outcomes and severity grading as per
      the Revised Atlanta Classification.
AB  - AIMS: To assess the severity of acute pancreatitis (AP) using computed tomography
      (CT) severity index (CTSI) and modified CT severity index (MCTSI), to correlate
      with clinical outcome measures, and to assess concordance with severity grading,
      as per the revised Atlanta classification (RAC). MATERIALS AND METHODS: In this
      prospective study approved by the Institutional Review Board (November 2014 to
      March 2016), sixty patients with AP (as per the RAC definition) underwent
      contrast-enhanced computed tomography (CECT) 5-11 days (median 6 days) after
      symptom onset. Two radiologists, blinded to clinical parameters, independently
      assessed CTSI and MCTSI (differences were resolved by consensus). Clinical
      outcome parameters included duration of stay in the hospital and intensive care
      unit (ICU), presence of persistent organ failure (OF), evidence of infection,
      need for intervention, and mortality. RESULTS: We included 60 cases [36 males,
      age range 19-65 (mean 37) years]. As per the RAC, 26 patients had mild AP, 12
      moderately severe, and 22 severe AP. According to CTSI and MCTSI, mild, moderate,
      and severe cases were 27 (45%), 19 (31.7%), 14 (23.3%) and 24 (40%), 10 (16.7%),
      26 (43.3%), respectively. MCTSI was concordant with the RAC grading in 54
      (90.0%), CTSI was concordant in 47 (78.3%), and both were concordant in 43
      (71.7%) cases. Area under the receiver-operating characteristic (ROC) curves
      (AUROC) was compared by the Hanley and McNeil method. Both CTSI and MCTSI were
      significantly associated with outcome parameters (P < 0.001), except duration of
      ICU stay. Sensitivity, specificity, positive predictive value (PPV), and accuracy
      of CTSI for detecting moderate/severe disease were 97.1%, 100%, 100%, and 98.3%
      respectively, and of MCTSI were 100%, 92.3%, 94.4%, and 96.7% respectively.
      CONCLUSION: Both CTSI and MCTSI showed significant correlation with clinical
      outcome parameters, and good concordance with RAC grading of severity. MCTSI
      showed a higher sensitivity but lower specificity than CTSI in differentiating
      mild from moderate/severe AP.

PMID- 28744076
TI  - MR fistulography with percutaneous instillation of aqueous jelly: A cost
      effective technique innovation.
AB  - BACKGROUND: Perianal fistula is a commonly encountered condition in routine
      surgical practice. Accurate presurgical mapping of these tracts is vital to
      prevent recurrence. We have assessed the effectiveness of percutaneous
      instillation of aqueous jelly prior to magnetic resonance (MR) fistulography.
      AIMS AND OBJECTIVES: To study the role of percutaneous instillation of aqueous
      jelly in fistulous tracts prior to MR fistulography. MATERIALS AND METHODS: All
      patients with active discharge, referred for MR fistulography between January
      2014 and April 2016, were included in this study. Approximately 3-5 ml of sterile
      aqueous jelly was percutaneously instilled into the external openings prior to MR
      fistulography. Post MR fistulography, patients were monitored till surgery for
      pain, fever, or bleeding. The type of fistulae, location of internal openings,
      lateral ramifications, and presence of abscess were compared with per operative
      findings for diagnostic accuracy. RESULTS: Sixty-four patients enrolled in our
      study had undergone preoperative MR fistulography with aqueous jelly
      instillation. MR fistulography revealed a total of 77 tracts and showed a
      sensitivity and specificity of 100% in delineation of type of tract. Forty-nine
      internal openings were identified with 94.2% sensitivity, 100% specificity, and
      95.3% accuracy. 90.5% sensitivity, 100% specificity, and accuracy of 97% were
      observed in delineation of lateral ramifications. None of the patients reported
      pain, fever, or bleeding post procedure till surgery. CONCLUSION: Percutaneous
      instillation of aqueous jelly prior to MR fistulography is a safe, cost
      effective, and accurate technique to provide a comprehensive delineation of the
      complex anatomy of perianal fistulae.

PMID- 28744077
TI  - Cystic lesions of the pancreatico-biliary tree: A schematic MRI approach.
AB  - Although a common occurrence, cystic lesions of the pancreatico-biliary tree
      (PBT) may pose a diagnostic dilemma because they encompass a large number of
      neoplastic and benign processes with varied clinical symptoms. Knowledge of
      lesion classification and characterization are essential in making an accurate
      prospective diagnosis. This is necessary for identifying clinically significant
      cystic masses, which at times may require invasive intervention from indolent,
      nonneoplastic lesions, for which surveillance may suffice. Today, there is an
      arsenal of modalities for assessing the PBT, however, magnetic resonance imaging
      (MRI) remains at the forefront for characterizing cystic morphology and fluid
      content, internal septations, solid component, enhancement patterns, as well as
      assessing the surrounding normal structures. This pictorial review aims to review
      the spectrum of MRI features, which will aid in the differential diagnoses of
      cystic lesions of the PBT and mimickers, enabling the radiologist to reach a more
      confident diagnosis.

PMID- 28744078
TI  - Partial anomalous hepatic venous drainage into left-sided atrium with right
      isomerism: A case report with review of literature.
AB  - Right isomerism, also known as Ivemark syndrome, is an unusual degree of symmetry
      of some of the abdominothoracic viscera reflecting bilateral right-sidedness. We
      report an exceedingly rare occurrence of anomalous drainage of the left hepatic
      vein to the left-sided atrium in a patient of right isomerism. With this case
      report, we further endorse that the isomerism of atrium might extend beyond the
      appendages, a view that has been long dismissed by the existing literature.

PMID- 28744079
TI  - Evaluation of patella alta using MRI measurements in adolescents.
AB  - PURPOSE: To determine whether or not there were any differences in the
      measurement techniques used by orthopedic and radiology specialists in the
      evaluation of magnetic resonance (MR) images for the diagnosis of patella alta in
      adolescents. MATERIALS AND METHODS: Evaluations were performed by three
      orthopedic specialists (Group I) and three radiology specialists (Group II)
      regarding the presence of patella alta in 40 adolescents cases using the Insall
      Salvati, Caton-Deschamps, Blackburne-Peel, and modified Insall-Salvati indices on
      MR images obtained to diagnose patellar instability. RESULTS: The Fleiss Kappa
      conformity levels for Insall-Salvati, Caton-Deschamps, Blackburne-Peel, and
      modified Insall-Salvati measurements were 0.531, 0.559, 0.246, and 0.272,
      respectively, in Group I, and 0.699, 0.346, 0.516, and 0.394, respectively, in
      Group II. CONCLUSION: The radiology specialists were found to have greater
      conformity in the evaluation of all patella alta indices, which was probably due
      to their greater familiarity with radiological measurements than that of the
      orthopedic specialists.

PMID- 28744080
TI  - Pelvic radiograph in skeletal dysplasias: An approach.
AB  - The bony pelvis is constituted by the ilium, ischium, pubis, and sacrum. The
      pelvic radiograph is an important component of the skeletal survey performed in
      suspected skeletal dysplasia. Most of the common skeletal dysplasias have either
      minor or major radiological abnormalities; hence, knowledge of the normal
      radiological appearance of bony pelvis is vital for recognizing the early signs
      of various skeletal dysplasias. This article discusses many common and some
      uncommon radiological findings on pelvic radiographs along with the specific
      dysplasia in which they are seen; common differential diagnostic considerations
      are also discussed.

PMID- 28744081
TI  - Early outcomes of radiofrequency ablation in unresectable metastatic colorectal
      cancer from a tertiary cancer hospital in India.
AB  - AIMS: The study was carried out to evaluate the early outcomes using
      Radiofrequency Ablation (RFA) for unresectable liver metastases in the management
      of metastatic colorectal cancer (mCRC) from an area of low endemicity. MATERIAL
      AND METHODS: 60 Patients with unresectable colorectal liver metastases had
      undergone 88 sessions of RFA from January 2007 till December 2013. The results
      were retrospectively analysed to evaluate the outcomes in terms of efficacy and
      survival rates. RESULTS: The median follow up of patients in our series was
      24.8months. 35/52 (67.3%) patients had complete response at 3 months while 8
      patients were lost to follow up. Of the 17 patients who had recurrence, 4 (23.5%)
      were at the ablated site while 13 patients (76.4%) progressed elsewhere.
      Abdominal pain was commonest post procedural symptom (20%). There was no
      procedure related mortality or any major complications. Mean disease free
      interval and Progression free survival was 6.7 and 13.1 months. Estimated median
      survival in patients with liver limited disease and those with small lesion
      (<3cm) was 3.79 years and 3.45 years respectively. Median survival in patients
      with lesion size 3-5 cms was 1.5 years. Annual survival rates would be 94.5%,
      55.2% and 26.2% for 1, 3 and 5 years. CONCLUSION: Radiofrequency ablation of
      unresectable liver metastases is effective in treatment of mCRC. Estimated
      survival rates and Annual survival rates at our institute from the low endemic
      region also follow the global trend. Size of the lesion was an important
      predictor of efficacy of RFA. Presence of extrahepatic disease and lesion size >3
      cm was associated with decreased survival.

PMID- 28744082
TI  - CT-guided percutaneous radiofrequency ablation of osteoid osteoma: Our experience
      in 87 patients.
AB  - PURPOSE: To evaluate the technical and clinical success of radiofrequency
      ablation of osteoid osteoma and analyze the factors responsible for clinical
      success. We also tried to investigate the role of follow-up computed tomography
      (CT) imaging. MATERIALS AND METHODS: This is a prospective study approved by the
      institute's ethics committee involving 87 patients with appendicular osteoid
      osteoma. CT-guided radio frequency ablation was performed using a bipolar
      ablation system. Patients were followed up over 15.4 (4-24) months for pain, and
      clinical success/failure was determined using established criteria. Patients with
      clinical failure were taken for repeat ablation. Follow-up CT was obtained at 6
      months and correlated with clinical success. Procedural scans were later reviewed
      for technical success in a blinded manner and correlated with clinical success
      along with other imaging and patient characteristics. RESULTS: Mean pre-procedure
      visual analog scale (VAS) score was 7.0 +/- 0.8. Primary success rate after
      single session was 86.2%(75/87 patients), and overall success rate after one/two
      sessions was 96.6%(84/87). No major complications were noted. Technical success
      rate was 89.7%(78/87). All 9 patients who had a suboptimal needle positioning had
      recurrence where as three patients had recurrence despite technical success. None
      of the imaging characteristics or history of prior intervention was significantly
      associated with clinical success. Follow-up CT showed advanced bone healing in 48
      lesions, and was confined to the treatment success group. Alternately,
      minimal/absent bone healing was seen in all (12) patients of primary treatment
      failure and 27 patients with treatment success. CONCLUSIONS: CT-guided
      percutaneous radio frequency ablation is a safe and highly effective treatment
      for osteoid osteomas even in recurrent and residual cases. Technical success is
      the most important parameter affecting the outcome. Post radio frequency ablation
      CT findings have a good positive but a poor negative predictive value in
      prognostication.

PMID- 28744083
TI  - Imaging features of vascular compression in abdomen: Fantasy, phenomenon, or true
      syndrome.
AB  - Vascular structures in the abdomen can compress or be compressed by adjacent
      structures. Classic imaging findings of vascular compressions, including median
      arcuate ligament syndrome, superior mesenteric artery syndrome, nutcracker
      syndrome, portal biliopathy, May-Thurner syndrome, and ureteropelvic junction
      obstruction will be discussed here. It is important to correlate imaging findings
      and clinical data to identify asymptomatic vascular compression which requires no
      treatment, intermittent vascular compression with nonspecific or vague clinical
      manifestation, and the subset of patients with true syndromes who will benefit
      from treatment.

PMID- 28744084
TI  - Singular observation of a desirable change after bronchial artery embolization
      for hemoptysis in intracavitary aspergilloma.
AB  - Aspergillomas are fungal balls developing in pre-existing lung cavities, which
      are most commonly secondary to tuberculosis. Aspergillomas can cause hemoptysis
      due to erosion of the blood vessels in cavity walls, which can often be
      recurrent, massive, and life-threatening. Bronchial artery embolization is
      considered to be the treatment of choice for short-term control of hemoptysis,
      and lobectomy as the definitive treatment for aspergilloma. We present a unique
      observation in two cases of aspergilloma where the fungal balls disappeared
      radiologically after bronchial artery embolization performed for massive
      hemoptysis.

PMID- 28744085
TI  - Role of exponential apparent diffusion coefficient in characterizing breast
      lesions by 3.0 Tesla diffusion-weighted magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the role of exponential apparent diffusion coefficient
      (ADC) as a tool for differentiating benign and malignant breast lesions. PATIENTS
      AND METHODS: This prospective observational study included 88 breast lesions in
      77 patients (between 18 and 85 years of age) who underwent 3T breast magnetic
      resonance imaging (MRI) including diffusion-weighted imaging (DWI) using b-values
      of 0 and 800 s/mm2 before biopsy. Mean exponential ADC and ADC of benign and
      malignant lesions obtained from DWI were compared. Receiver operating
      characteristics (ROC) curve analysis was undertaken to identify any cut-off for
      exponential ADC and ADC to predict malignancy. P value of <0.05 was considered
      statistically significant. Histopathology was taken as the gold standard.
      RESULTS: According to histopathology, 65 lesions were malignant and 23 were
      benign. The mean ADC and exponential ADC values of malignant lesions were 0.9526
      +/- 0.203 * 10-3 mm2/s and 0.4774 +/- 0.071, respectively, and for benign lesions
      were 1.48 +/- 0.4903 * 10-3 mm2/s and 0.317 +/- 0.1152, respectively. For both
      the parameters, differences were highly significant (P < 0.001). Cut-off value of
      <=0.0011 mm2/s (P < 0.0001) for ADC provided 92.3% sensitivity and 73.9%
      specificity, whereas with an exponential ADC cut-off value of >0.4 (P < 0.0001)
      for malignant lesions, 93.9% sensitivity and 82.6% specificity was obtained. The
      performance of ADC and exponential ADC in distinguishing benign and malignant
      breast lesions based on respective cut-offs was comparable (P = 0.109).
      CONCLUSION: Exponential ADC can be used as a quantitative adjunct tool for
      characterizing breast lesions with comparable sensitivity and specificity as that
      of ADC.

PMID- 28744086
TI  - Differentiation of secondary involvement of the breast by lymphoreticular
      malignancy from fibroadenoma using ultrasound elastography: A report of two
      cases.
AB  - Extramedullary lymphoma infiltration of the breast by lymphoblastic lymphoma is
      very rare and most cases are of B-cell lineage; T-cell neoplasms represent less
      than 10% of all breast lymphomas. Here, we report one patient with lymphoblastic
      lymphoma and one patient with leukemia, who have similar lesions in breasts with
      different ultrasound elastography findings. Ultrasound-guided tru-cut biopsies
      were performed and the first lesion was confirmed as lymphoma infiltration and
      the second as fibroadenoma. In cases of breast mass presence in patients with a
      history of hematologic malignancies such as lymphoma or leukemia, breast
      infiltration should be kept in mind. Elastography findings can assist in the
      differentiation of these lesions and further investigations or biopsies can be
      avoided.

PMID- 28744087
TI  - A peek into the future of radiology using big data applications.
AB  - Big data is extremely large amount of data which is available in the radiology
      department. Big data is identified by four Vs - Volume, Velocity, Variety, and
      Veracity. By applying different algorithmic tools and converting raw data to
      transformed data in such large datasets, there is a possibility of understanding
      and using radiology data for gaining new knowledge and insights. Big data
      analytics consists of 6Cs - Connection, Cloud, Cyber, Content, Community, and
      Customization. The global technological prowess and per-capita capacity to save
      digital information has roughly doubled every 40 months since the 1980's. By
      using big data, the planning and implementation of radiological procedures in
      radiology departments can be given a great boost. Potential applications of big
      data in the future are scheduling of scans, creating patient-specific
      personalized scanning protocols, radiologist decision support, emergency
      reporting, virtual quality assurance for the radiologist, etc. Targeted use of
      big data applications can be done for images by supporting the analytic process.
      Screening software tools designed on big data can be used to highlight a region
      of interest, such as subtle changes in parenchymal density, solitary pulmonary
      nodule, or focal hepatic lesions, by plotting its multidimensional anatomy.
      Following this, we can run more complex applications such as three-dimensional
      multi planar reconstructions (MPR), volumetric rendering (VR), and curved planar
      reconstruction, which consume higher system resources on targeted data subsets
      rather than querying the complete cross-sectional imaging dataset. This pre
      emptive selection of dataset can substantially reduce the system requirements
      such as system memory, server load and provide prompt results. However, a word of
      caution, "big data should not become "dump data" due to inadequate and poor
      analysis and non-structured improperly stored data. In the near future, big data
      can ring in the era of personalized and individualized healthcare.

PMID- 28744088
TI  - IgG4-Related disease simulating paraneoplastic syndrome: Role of 18FDG PET/CT
      imaging.
AB  - Immunoglobulin G4 (IgG4)-related systemic disease (IgG4-RSD) is a new systemic
      entity associated with autoimmune pancreatitis (AIP). Other organ involvements
      take the form of sclerosing cholangitis, sclerosing cholecystitis, sclerosing
      sialadenitis, retroperitoneal fibrosis, and interstitial nephritis. Recently,
      lung diseases related to IgG4 have been described to occur with or without other
      organ involvement. These diseases include interstitial lung disease (ILD),
      pulmonary inflammatory pseudotumor, and lymphomatoid granulomatosis. Most of
      these cases occur in combination with AIP, which also appears to have a general
      preponderance for males. The true incidence of IgG4-related ILD and the incidence
      of AIP are unknown. Here, we describe a case of a 53-year-old gentleman who
      presented with weight loss, fever, loose motions, altered sensorium, and
      persistent low hemoglobin, for which he was referred for 18-fluorodeoxyglucose
      positron emission tomography/computed tomography scan to diagnose probable
      underlying occult malignancy/paraneoplastic syndrome. It revealed features
      suggestive of IgG4 disease involving the pancreas and lungs, which was confirmed
      subsequently.

PMID- 28744089
TI  - Iatrogenic buffalo-chest syndrome.

PMID- 28744090
TI  - Hard metal lung disease: Unexpected CT findings.

PMID- 28744091
TI  - Author reply.

PMID- 28744092
TI  - Using MALDI-TOF-MS to test Staphylococcus aureus-infected vitreous.
AB  - PURPOSE: This study aimed to establish a method for testing Staphylococcus aureus
      in the vitreous of endophthalmitis with matrix-assisted laser
      desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), which is
      simple, fast, and sensitive. METHODS: S. aureus at different numbers was either
      mixed with homogenized vitreous or inoculated in porcine eyes for culturing,
      followed by homogenization. The homogenized vitreous samples, with or without
      centrifugation, were stained with Gram and Coomassie Blue (CBB) dyes and cultured
      with blood agar. The pellet of the vitreous mixture was analyzed with MALDI-TOF
      MS. RESULTS: The minimum detectable levels of S. aureus in H2O and in the pellet
      of homogenized vitreous were 9.0 * 103 (positive rate, 22.2%) and 1.0 * 104
      CFU/MUl (positive rate, 11.1%), respectively. In the vitreous samples inoculated
      with S. aureus and cultured for 12 h, the number of S. aureus increased in a dose
      dependent manner to the number of bacteria in the inoculate. In the supernatant
      of the homogenized vitreous, there were traces of bacteria identified with Gram
      staining. On the blood agar plates, the supernatant grew a few colonies, while
      the pellet grew intensive colonies. The vitreous fragments that were stained with
      CBB were displayed in the supernatants, in small numbers, and in the pellets.
      When the inoculated number was 1.0 * 104 CFU/MUl or higher, the bacteria in the
      vitreous pellets could be identified in all samples (100%, n = 9). However,
      bacteria could be detected in only two out of nine spots of pellets (22.2%) if
      the number of inoculated S. aureus was 1.0 * 103 CFU/MUl. CONCLUSIONS: A method
      for testing S. aureus directly from vitreous samples of endophthalmitis by the
      combination of easy extraction methods and a MALDI-TOF- MS assay was provided.
      This rapid identification method is easily adaptable for use in clinical routine
      and can help reduce the delay in diagnosis, allowing for earlier therapeutic
      intervention in patients.

PMID- 28744093
TI  - Origins of the phototransduction delay as inferred from stochastic and
      deterministic simulation of the amplification cascade.
AB  - PURPOSE: To identify steps of the phototransduction cascade responsible for the
      delay of the photoresponse. METHODS: Electrical responses of fish (Carassius)
      cones and Rana ridibunda frog rods and cones were recorded with a suction pipette
      technique and as an aspartate-isolated mass receptor potential from isolated
      perfused retinas. Special attention was paid to sufficiently high temporal
      resolution (1-ms flash, 700 Hz amplification bandpass). Stochastic simulation of
      the activation steps from photon absorption to the formation of catalytically
      active phosphodiesterase (PDE) was performed. In addition, a deterministic
      mathematical model was fit to the experimental responses. The model included a
      detailed description of the activation steps of the cascade that enabled
      identification of the role of individual transduction stages in shaping the
      initial part of the response. RESULTS: We found that the apparent delay of the
      photoresponse gets shorter with increasing stimulus intensity and reaches an
      asymptotic value of approximately 3 ms in cones and greater than or equal to 10
      ms in rods. The result seems paradoxical since it is suggested that the delay
      occurs in the chain of steps from photon absorption to the formation of active
      transducin (T*) which in cones is, on average, slower than in rods. Stochastic
      simulation shows that actually the steps from photon absorption to T* may not
      contribute perceptibly to the delay. Instead, the delay occurs at the stage that
      couples the cycle of repetitive activation of T by rhodopsin (R*) with the
      activation of PDE. These steps include formation of T* (= T alpha GTP) out of T
      alphabetagamma GTP released from the activation cycle and the subsequent
      interaction of T* with PDE. This poses a problem. The duration of an average
      cycle of activation of T in rods is approximately 5 ms and is determined by the
      frequency of collisions between R* and T in the photoreceptor membrane. The
      frequency is roughly proportional to the surface packing density of T in the
      membrane. As the packing density of PDE is approximately 12 times lower than that
      of T, it could be expected that the rate of the T*-PDE interaction were an order
      of magnitude slower than that of R* and T. As modeling shows, this is the case in
      rods. However, the delay in cones is approximately 3 ms which could be achieved
      only at a T*-PDE interaction time of less than or equal to 5 ms. This means that
      either the frequency of the collisions of T* and PDE, or the efficiency of
      collisions, or both in cones are approximately ten times higher than in rods.
      This may be a challenge to the present model of the molecular organization of the
      photoreceptor membrane. CONCLUSIONS: The delay of the photoresponse is mainly set
      by the rate of interaction of T* with PDE. In cones, the delay is shorter than in
      rods and, moreover, shorter than the duration of the cycle of repetitive
      activation of T by R*. This poses a problem for the present model of diffusion
      interaction of phototransduction proteins in the photoreceptor membrane.

PMID- 28744094
TI  - Patient considerations in ocular hypertension: role of bimatoprost ophthalmic
      solution.
AB  - Glaucoma is a leading cause of irreversible blindness worldwide. The reduction of
      intraocular pressure has been well established as an effective treatment to
      prevent both the development and the progression of all forms of glaucoma.
      Bimatoprost 0.03% ophthalmic solution, introduced in 2001, is a synthetic
      prostamide with the unique mechanism of improving both uveoscleral and trabecular
      outflow. Comparative studies with other pharmacotherapies have shown favorable
      results for bimatoprost as a potent ocular hypotensive agent that is generally
      well tolerated. Common side effects include conjunctival hyperemia, eyelash
      growth, iris pigmentation and periorbital changes. Hyperemia rates were reduced
      following the introduction of bimatoprost 0.01%. Bimatoprost should be used with
      caution in those with higher risk of developing ocular inflammation and macular
      edema. However, the perceived risk of bimatoprost in these patient populations is
      likely greater than the actual risk observed in practice. Bimatoprost is
      currently in the center of several clinical trials including its use for
      dermatologic applications and sustained-release therapies for the treatment of
      ocular hypertension and glaucoma.

PMID- 28744095
TI  - Agreement on the evaluation of glaucomatous optic nerve head findings by
      ophthalmology residents and a glaucoma specialist.
AB  - OBJECTIVES: To assess agreement among ophthalmology residents and a glaucoma
      expert in the evaluation of cross-sectional glaucomatous optic nerve head
      characteristics using stereoscopic photographs. METHODS: Twenty stereo
      photographs were analyzed by ophthalmology residents just after completion of
      their first (First-Year Group) or third (Third-Year Group) year of residency and
      by a glaucoma expert. The agreement was assessed using the kappa statistic
      (kappa) and limits of agreement. RESULTS: Agreement among resident groups and the
      expert ranged from poor to moderate. Agreement between Third Years and the expert
      seems to be better than that between First Years and the expert, especially in
      the evaluation of "nasal cupping", "barring circumlinear vessel," "notching", and
      "retinal nerve fiber layer defect" criteria. However, no improvement was seen in
      the agreement with the expert regarding glaucomatous optic neuropathy, which was
      64% (kappa=0.19) for First Years and 63% (kappa=0.20) for Third Years.
      CONCLUSION: Agreement between residents and the expert was poor to moderate and
      similar when comparing both groups. This may suggest that the residents learn how
      to identify glaucoma signals during the first year of training, and the results
      of this study may facilitate the creation of targeted teaching tools in residency
      training.

PMID- 28744096
TI  - Subjective evaluation of uncorrected vision in patients undergoing cataract
      surgery with (diffractive) multifocal lenses and monovision.
AB  - PURPOSE: To analyze patient satisfaction and difficulties with bilateral
      multifocal intraocular lenses (IOLs) implantation and aspheric monofocal IOLs
      implantation using monovision, after cataract surgery. MATERIALS AND METHODS: A
      total of 61 participants were included in the study, 29 with monovision and 32
      with multifocal lenses. The inclusion criteria were patients undergoing
      phacoemulsification for bilateral visual impairment due to cataracts and
      presenting with postoperative visual acuity of 20/30 or better for distance and
      line J3 or better for near vision. RESULTS: The 2 groups had similar results
      regarding difficulties with daily activities such as distance vision, near
      vision, watching television, reading, cooking, using a computer or cellphone,
      shaving/putting on makeup and shopping. There were differences in responses
      between the groups regarding difficulty with night vision (P=0.0565) and night
      driving (P=0.0291). Degree of satisfaction in terms of distance vision without
      glasses was statistically significantly better in monovision group (P=0.0332),
      but not for near (P=0.9101). CONCLUSION: Both techniques yielded satisfactory
      results regarding visual acuity for different activities without the need to use
      glasses. Multifocal lenses are a good option for patients with the exception of
      night driving, and who desire independence from glasses.

PMID- 28744097
TI  - Comparison of corneal power obtained from VERION image-guided surgery system and
      four other devices.
AB  - PURPOSE: To assess the corneal keratometric values obtained using the VERION
      image-guided surgery system and other devices. METHODS: This study evaluated the
      right eyes of 115 cataract patients before intraocular lens (IOL) implantation
      through consecutive tests using 5 devices: VERION Reference Unit, Placido-based
      corneal topography (OPD-Scan III), monochromatic light-emitting diodes (LenStar
      LS900 and AL-Scan), and rotary prism technology (auto kerato-refractometer KR
      8800). Analyzed parameters were corneal steep and flat keratometric values (Ks
      and Kf) and corneal astigmatism and axis. These parameters were evaluated using
      the one-sample two-tailed t-test and the 95% limits of agreement (95% LOAs)
      between the devices. RESULTS: The mean corneal cylinder value measurements were 
      0.97+/-0.63 D, -0.88+/-0.60 D, -0.90+/-0.69 D, -0.90+/-0.67 D, and -0.83+/-0.60 D
      with VERION, LenStar, AL-Scan (2.4 mm), OPD III, and KR-8800, respectively. Only
      KR-8800 showed a significant difference from VERION in the corneal cylinder value
      (P<0.05). The mean differences in the Kf and Ks of VERION compared to those of
      OPD III were 0.18+/-0.45 D and 0.17+/-0.38 D (P<0.05), respectively. The 95% LOAs
      of Bland-Altman analysis for the corneal astigmatism axis of the VERION with
      LenStar, AL-Scan (2.4 mm), OPD III, and KR-8800 were -26.25 degrees  to 58.71
      degrees , -20.61 degrees  to 47.44 degrees , -25.03 degrees  to 58.98 degrees ,
      and -27.85 degrees  to 65.17 degrees , respectively. CONCLUSION: None of the
      VERION parameters were significantly different from those of AL-Scan and LenStar.
      AL-Scan (2.4 mm zone) was especially similar to VERION. Wide LOAs are potential
      contributors to axis error in patients with toric IOL implants.

PMID- 28744098
TI  - Spotlight on brodalumab in the treatment of moderate-to-severe plaque psoriasis:
      design, development, and potential place in therapy.
AB  - Brodalumab is a novel fully human immunoglobulin G2 monoclonal antibody that
      antagonizes the interleukin (IL)-17 pathway by binding with high affinity to
      human IL-17RA. The role of IL-17A in the pathogenesis of psoriasis, as well as
      the remarkable effectiveness of IL-17 inhibitors in the treatment of moderate-to
      severe plaque psoriasis, is well established. The mechanism of action of
      brodalumab is unique in that it inhibits the IL-17 receptor compared to the two
      other currently FDA-approved IL-17 inhibitors, secukinumab and ixekizumab, which
      inhibit the IL-17A molecule itself. The efficacy of brodalumab in the treatment
      of moderate-to-severe plaque psoriasis has been demonstrated in phase 2 and 3
      trials, and subsequently the FDA approved this medication in February 2017.
      Brodalumab was approved in Japan in July 2016 and approval is pending in Europe.
      The safety and adverse effects of brodalumab were reviewed across several
      clinical trials, which, similar to other IL-17 inhibitors, demonstrated increased
      rates of neutropenia and Candida infections. Brodalumab treatment, similar to
      ixekizumab and secukinumab, showed no improvement in inflammatory bowel disease
      patients, and on the contrary, more exacerbations were encountered. Suicidal
      ideation and behavior events have been reported with brodalumab treatment and are
      of significant concern. Brodalumab provides another highly effective treatment
      option for moderate-to-severe plaque psoriasis.

PMID- 28744099
TI  - Pharmacokinetics, pharmacodynamics, and tolerability of verinurad, a selective
      uric acid reabsorption inhibitor, in healthy adult male subjects.
AB  - PURPOSE: Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in
      clinical development for the treatment of gout and asymptomatic hyperuricemia.
      The aim of this study was to evaluate the pharmacokinetics, pharmacodynamics, and
      tolerability of verinurad in healthy adult males. SUBJECTS AND METHODS: This was
      a Phase I, randomized, double-blind, placebo-controlled, single and multiple
      ascending dose study. Panels of eight male subjects received a single oral dose
      of verinurad or placebo in either a fasted or fed state; panels of 10-12 male
      subjects received ascending doses of once-daily verinurad or placebo in a fasted
      state for 10 days. Serial blood and urine samples were assayed for verinurad and
      uric acid. Safety was assessed by adverse event (AE) reports, laboratory tests,
      vital signs, and electrocardiograms (ECGs). RESULTS: A total of 81 adult males
      completed the study. Following single doses of verinurad, maximum observed plasma
      concentration (Cmax) and area under the plasma concentration-time curve (AUC)
      increased in a dose-proportional manner; Cmax occurred at 0.5-0.75 hours and 1.25
      hours in the fasted and fed states, respectively. Food decreased AUC by 23% and
      Cmax by 37%-53%. There was a modest accumulation of verinurad following multiple
      daily doses. Verinurad reduced serum urate levels by up to 62% (40 mg, single
      dose) and 61% (10 mg, multiple dose). The increase in urinary excretion of uric
      acid was greatest in the first 6 hours after dosing and was still evident >=24
      hours for verinurad doses >=2 mg. Verinurad was well tolerated at all doses. No
      serious AEs, severe AEs, discontinuations due to AEs, or clinically significant
      laboratory or ECG abnormalities were reported. CONCLUSION: Single and multiple
      doses of verinurad were well tolerated, absorption was rapid, and exposure was
      dose proportional. Verinurad increased urinary uric acid elimination and resulted
      in sustained reductions in serum urate. These data support further clinical
      evaluation of once-daily verinurad as a treatment for gout.

PMID- 28744100
TI  - Evaluation of the stability of linezolid in aqueous solution and commonly used
      intravenous fluids.
AB  - PURPOSE: The aim was to evaluate the stability of linezolid in commonly used
      intravenous fluids and in aqueous solution to determine the kinetics of
      degradation and shelf-life values at alkaline pH values. METHODS: Forced
      degradation studies were performed on linezolid in solution to develop a
      validated high-performance liquid chromatography analysis. Sodium chloride 0.9%,
      sodium lactate, and glucose 5% and glucose 10% solution containing 2.0 mg/mL
      linezolid were stored at 25.0 degrees C (+/-0.1 degrees C) for 34 days. The
      effect of temperature on the stability of linezolid in 0.1 M sodium hydroxide
      solution was investigated to determine the activation energy. The degradation
      rates of linezolid at selected pH values at 70.0 degrees C and the influence of
      ionic strength were also examined. Activation energy data were applied to
      determine the shelf-life values at selected pH values, and a pH rate profile was
      constructed over the pH range of 8.7-11.4. The stability of intravenous linezolid
      (Zyvox(r)) solution was evaluated by storing at 70.0 degrees C for 72 hours.
      RESULTS: Linezolid was found to maintain >95.0% of its initial concentration
      after storage at 25.0 degrees C for 34 days in sodium lactate, 0.9% in sodium
      chloride, and 5% and 10% in glucose solutions. Linezolid was degraded at alkaline
      pH values by first-order kinetics. Activation energy data showed that
      temperature, but not ionic strength, influenced the degradation rate
      significantly. An activation energy of 58.22 kJ/mol was determined for linezolid
      in 0.1 M sodium hydroxide solution. Linezolid was least stable at high pH values
      and at elevated temperatures. It was determined that linezolid has adequate
      stability for the preparation of intravenous fluids for clinical administration.
      CONCLUSION: Linezolid was found to have a shelf life of 34 days at 25 degrees C
      when added to sodium lactate, 0.9% sodium chloride, and 5% and 10% glucose
      solutions. It was least stable at high pH values and at elevated temperatures.

PMID- 28744101
TI  - A 6-month mixed-effect pharmacokinetic model for post-transplant intravenous anti
      hepatitis B immunoglobulin prophylaxis.
AB  - BACKGROUND: Although individualized dosage regimens for anti-hepatitis B
      immunoglobulin (HBIG) therapy have been suggested, the pharmacokinetic profile
      and factors influencing the basis for individualization have not been
      sufficiently assessed. We sought to evaluate the pharmacokinetic characteristics
      of anti-HBIG quantitatively during the first 6 months after liver
      transplantation. METHODS: Identical doses of 10,000 IU HBIG were administered to
      adult liver transplant recipients daily during the first week, weekly thereafter
      until 28 postoperative days, and monthly thereafter. Blood samples were obtained
      at days 1, 7, 28, 84, and 168 after transplantation. Plasma HBIG titer was
      quantified using 4 different immunoassay methods. The titer determined by each
      analytical method was used for mixed-effect modeling, and the most precise
      results were chosen. Simulations were performed to predict the plausible
      immunoglobulin maintenance dose. RESULTS: HBIG was eliminated from the body most
      rapidly in the immediate post-transplant period, and the elimination rate
      gradually decreased thereafter. In the early post-transplant period, patients
      with higher DNA titer tend to have lower plasma HBIG concentrations. The
      maintenance doses required to attain targets in 90%, 95%, and 99% of patients
      were ~15.3, 18.2, and 25.1 IU, respectively, multiplied by the target trough
      level (in IU/L). CONCLUSION: The variability (explained and unexplained) in HBIG
      pharmacokinetics was relatively larger in the early post-transplant period. Dose
      individualization based upon patient characteristics should be adjusted focusing
      quantitatively on the early post-transplant period.

PMID- 28744102
TI  - Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax(r)
      tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three
      way, reference-replicated crossover study.
AB  - PURPOSE: The aim of this study was to evaluate the bioequivalence of a generic
      product 70 mg alendronate sodium tablets with the reference product Fosamax(r) 70
      mg tablet. MATERIALS AND METHODS: A single-center, open-label, randomized, three
      period, three-sequence, reference-replicated crossover study was performed in 36
      healthy Chinese male volunteers under fasting conditions. In each study period,
      the volunteers received a single oral dose of the generic or reference product
      (70 mg). Blood samples were collected at pre-dose and up to 8 h after
      administration. The bioequivalence of the generic product to the reference
      product was assessed using the US Food and Drug Administration (FDA) and European
      Medicines Agency (EMA) reference-scaled average bioequivalence (RSABE) methods.
      RESULTS: The average maximum concentrations (Cmax) of alendronic acid were
      64.78+/-43.76, 56.62+/-31.95, and 60.15+/-37.12 ng/mL after the single dose of
      the generic product and the first and second doses of the reference product,
      respectively. The areas under the plasma concentration-time curves from time 0 to
      the last timepoint (AUC0-t ) were 150.36+/-82.90, 148.15+/-85.97, and 167.11+/
      110.87 h?ng/mL, respectively. Reference scaling was used because the within
      subject standard deviations of the reference product (sWR ) for Cmax and AUC0-t
      were all higher than the cutoff value of 0.294. The 95% upper confidence bounds
      were -0.16 and -0.17 for Cmax and AUC0-t , respectively, and the point estimates
      for the generic/reference product ratio were 1.08 and 1.00, which satisfied the
      RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0-t were 90.35%
      129.04% and 85.31%-117.15%, respectively, which were within the limits of the EMA
      for the bioequivalence of 69.84%-143.19% and 80.00%-125.00%. CONCLUSION: The
      generic product was bioequivalent to the reference product in terms of the rate
      and extent of alendronate absorption after a single 70 mg oral dose under fasting
      conditions.

PMID- 28744103
TI  - Clinical utility of evolocumab in the management of hyperlipidemia: patient
      selection and follow-up.
AB  - Inhibition of PCSK9 is a novel therapeutic strategy aimed at reducing low-density
      lipoprotein cholesterol (LDL-C) and cardiovascular risk. Evolocumab is a fully
      humanized monoclonal antibody that inhibits PCSK9, an enzyme that binds to LDL
      receptors and prevents them from recycling to the hepatocyte surface. Clinical
      trials have demonstrated 50%-70% reductions in LDL-C with evolocumab when used in
      combination with statin therapy. The recent FOURIER trial demonstrated that
      evolocumab further reduces cardiovascular events, but not mortality, in high-risk
      patients already receiving statin therapy. Furthermore, evolocumab did not affect
      neurocognitive function and was not associated with antidrug-antibody production
      in over 60,000 patient-years of drug exposure. Appropriate candidates for
      evolocumab primarily are individuals at high cardiovascular risk, including those
      with familial hypercholesterolemia and/or established cardiovascular disease, who
      are already on statin therapy. At this time, the use of evolocumab monotherapy
      seems appropriate only for individuals deemed statin-intolerant despite
      attempting several statins. Consideration must be given toward patient
      willingness to self-inject evolocumab and issues concerning third-party coverage,
      given the current costs of evolocumab.

PMID- 28744104
TI  - Efficacy and safety of direct-acting antiviral therapy in previous hard-to-treat
      patients with recurrent hepatitis C virus infection after liver transplantation:
      a real-world cohort.
AB  - BACKGROUND: Recurrent hepatitis C virus (HCV) infection after liver
      transplantation (LT) has been a frequent and relevant problem in the past two
      decades. This analysis evaluated the efficacy and safety of new interferon (IFN)
      free direct-acting antiviral (DAA) therapies in a large real-world cohort of HCV
      patients after LT. METHODS: We retrospectively analyzed a cohort of 157 patients
      infected with HCV who underwent deceased donor LT between 1997 and 2014. Patient
      survival, outcome, and side effects of antiviral therapy were assessed. RESULTS:
      Survival with recurrent HCV genotype 1 (GT1) infection was inferior to other HCV
      GTs (P=0.01). The overall sustained virological response (SVR) rate with new DAA
      therapy was 94.6% (n=37). Patients with both GT1 and other GTs reached SVR rates
      >90%. We noticed a few side effects, mainly caused by ribavirin, and only one
      discontinuation in DAA-treated patients. CONCLUSION: DAA therapy was effective
      and safe in previous hard-to-treat patients after LT in this real-world cohort.

PMID- 28744105
TI  - Pattern of statin use changes following media coverage of its side effects.
AB  - BACKGROUND: The media plays a role in shaping opinions about medical decisions,
      for example, whether to initiate or stop treatment. An association between
      negative media attention and statin discontinuation has been demonstrated, but it
      may differ depending on the reason for prescription and whether the user is new
      (incident) or long term (prevalent). AIM: The aim of this study is to explore
      whether a Danish newspaper article featuring the side effects of statins affects
      statin discontinuation in incident versus prevalent users, with the reason for
      prescription also taken into account. METHODS: The study relies on a quasi
      experimental design and uses registry data on statin purchases to explore
      discontinuation and treatment duration. As a proxy for reason for prescription,
      data on filled prescriptions and hospital diagnoses from a Danish registry were
      used. We compared statin discontinuation in all statin users in Denmark in 2007
      before the media event (n=343,438) and after it in 2008 (n=404,052). RESULTS:
      Compared to 2007, statin discontinuation among prevalent users in 2008 increased
      by 2.97 percentage points (pp). The change in discontinuation varied with the
      indication for statin use. Those with myocardial infarction had the smallest
      increase (1.98 pp) and those with hypercholesterolemia or primary hypertension
      had the largest increase (3.54 pp). Incident statin users had a higher level of
      discontinuation and a larger difference in discontinuation between 2007 and 2008.
      Compared to 2007, more people (5.52 pp) discontinued statin treatment in 2008.
      Again, those with myocardial infarction had the smallest decrease in statin
      discontinuation (1.49 pp), while those with a potential atherosclerotic condition
      (7.05 pp) and hypercholesterolemia or primary hypertension (6.10 pp) had the
      largest increase. CONCLUSION: Statin discontinuation increased in 2008 following
      a media event, but especially among individuals prescribed statins for primary
      prevention and among new statin users.

PMID- 28744106
TI  - Evaluating patient preference and satisfaction for human immunodeficiency virus
      therapy in France.
AB  - OBJECTIVES: The objectives were 1) to elicit relative preferences for attributes
      of antiretroviral therapies (ART) in people living with HIV (PLWH) and 2) to
      explore satisfaction and adherence with current ART. PATIENTS AND METHODS: We
      conducted a multicenter cross-sectional study, consecutively enrolling PLWH
      receiving an ART. The quantitative part estimated the strength of preference for
      different attributes using an online discrete choice experiment (DCE). DCE data
      were analyzed using a mixed logit regression model. Qualitative data were
      collected through individual interviews. A preliminary coding framework was
      developed which was then further refined and applied during thematic analysis of
      factors influencing satisfaction and adherence. RESULTS: A total of 101 PLWH took
      part in the quantitative part and 31 in the qualitative part. Over 90% had an
      undetectable viral load. Quantitative data revealed a strong preference for a
      treatment with limited drug-drug interactions, diarrhea and long-term health
      problems (P<0.0001), and that did not need to be taken on an empty stomach
      (P<0.0001). Patients also preferred to avoid problems associated with treatment
      failure (P<0.0001) or one that left them with a higher viral load after the first
      weeks of treatment (P=0.044). Differences in CD4 cell count, and pills that must
      be taken with food were not significant drivers of treatment choice. The strength
      of these attributes was reflected in the qualitative data, highlighting the
      importance patients place on treatment efficacy, and also suggesting that some of
      these attributes may impact adherence. Many factors influencing adherence and
      satisfaction with treatment were identified, including pill size, worry about
      sexual transmission and impact on social life. CONCLUSION: Most of the attributes
      included in this survey were important to participants when choosing an ART, in
      particular those related to quality of life, and these should be taken into
      account in order to optimize adherence and satisfaction.

PMID- 28744107
TI  - A cohort of French pediatric patients with primary immunodeficiencies: are
      patient preferences regarding replacement immunotherapy fulfilled in real-life
      conditions?
AB  - OBJECTIVE: To assess quality of life and satisfaction regarding immunoglobulin
      replacement therapy (IgRT) treatment according to the route (intravenous Ig
      [IVIg] or subcutaneous Ig [SCIg]) and place of administration (home-based IgRT or
      hospital-based IgRT). SUBJECTS AND METHODS: Children 5-15 years old treated for
      primary immunodeficiency disease (PIDD) with IgRT for >=3 months were included in
      a prospective, noninterventional cohort study and followed over 12 months.
      Quality of life was assessed with the Child Health Questionnaire - parent form
      (CHQ-PF)-50 questionnaire. Satisfaction with IgRT was measured with a three
      dimensional scale (Life Quality Index [LQI] with three components: factor I [FI],
      treatment interference; FII, therapy-related problems; FIII, therapy settings).
      RESULTS: A total of 44 children (9.7+/-3.2 years old) receiving IgRT for a mean
      of 5.6+/-4.5 years (median 4.1 years) entered the study: 18 (40.9%) were
      receiving hospital-based IVIg, two (4.6%) were receiving home-based IVIg, and 24
      (54.6%) were treated by home-based SCIg. LQI FIII was higher for home-based SCIg
      than for hospital-based IVIg (P=0.0003), but there was no difference for LQI FI
      or LQI FII. LQI FIII significantly improved in five patients who switched from
      IVIg to SCIg during the follow-up when compared to patients who pursued the same
      regimen (either IVIg or SCIg). No difference was found on CHQ-PF50 subscales, LQI
      FI, or LQI FII. CONCLUSION: Home-based SCIg gave higher satisfaction regarding
      therapy settings than hospital-based IVIg. No difference was found on other
      subscales of the LQI or CHQ-PF50 between hospital-based IVIG and home-based SCIG.

PMID- 28744108
TI  - Patient adherence to subcutaneous IFN beta-1a injections using the RebiSmart(r)
      injection device: a retrospective real-world study among Dutch and German
      patients with multiple sclerosis.
AB  - PURPOSE: Long-term treatment adherence among patients with multiple sclerosis
      (MS) is a general concern, with an established correlation with clinical
      efficacy. Closely monitoring patients' treatment behavior may have a beneficial
      effect on adherence. This study assessed adherence, in daily life, to
      subcutaneous (sc) IFN beta-1a, self-administered using the RebiSmart(r)
      electronic injection device (the IFN beta-Ia autoinjector device), in patients
      with MS. PATIENTS AND METHODS: This was a retrospective observational study
      analyzing treatment adherence based on injection data, eg, injection date and
      dose, extracted from the IFN beta-Ia autoinjector devices collected from patients
      in Germany and the Netherlands. RESULTS: Data recorded in the period from 2007 to
      2012 by the IFN beta-Ia autoinjector devices from 1,682 (79.7% from Germany,
      20.3% from the Netherlands) patients were analyzed. A mean of 94.8% of the multi
      dose cartridges (containing sc IFN beta-1a for three injections) were used
      completely, indicating a low incidence of application errors and drug wastage.
      The mean adherence rate was 90.7% and 82.9% over the entire observation period
      (mean treatment duration: 150.1 weeks). Median adherence rates were similar
      between German and Dutch patients (97.9% vs 99.0%). CONCLUSION: In daily clinical
      practice, patients using the IFN beta-Ia autoinjector device were highly adherent
      to sc IFN beta-1a. The injection data stored electronically in the device may
      help patients to adhere to treatment regimens and, if viewed by physicians,
      promote discussion of adherence issues with patients.

PMID- 28744109
TI  - Comparison of three types of central venous catheters in patients with malignant
      tumor receiving chemotherapy.
AB  - BACKGROUND: Central venous catheters (CVCs) have been an effective access for
      chemotherapy instead of peripherally intravenous catheters. There were limited
      studies on the choices and effects of different types of CVCs for chemotherapy.
      The aim of this study was to compare the complications, cost, and patients'
      quality of life and satisfaction of three commonly used CVCs for chemotherapy,
      such as implanted venous port, peripherally inserted central catheters (PICCs),
      and external non-tunneled central venous catheters (NTCs). METHODS: A double
      center prospective cohort study was carried out from March 2014 to December 2016.
      Catheterization situation, complications, catheter maintenance, cost, and
      patients' quality of life and satisfaction were recorded, investigated, and
      analyzed. Forty-five ports, 60 PICCs and 40 NTCs were included. All the CVCs were
      followed up to catheter removal. RESULTS: There was no statistical difference in
      catheterization success rates between port and PICC. NTC had less success rate by
      one puncture compared with port. Ports had fewer complications compared with
      PICCs and NTCs. The complication rates of ports, PICCs and NTCs were 2.2%, 40%,
      and 27.5%, respectively. If the chemotherapy process was <12 months, NTCs cost
      least, and the cost of port was much higher than PICC and NTC. When the duration
      time was longer than 12 months, the cost of port had no difference with the cost
      of PICC. Quality of life and patients' satisfaction of port group were
      significantly higher than the other two groups. CONCLUSION: Although port
      catheterization costs more and needs professional medical staff and strict
      operational conditions, ports have fewer complications and higher quality of life
      and patients' satisfaction than PICCs and NTCs. Therefore, not following
      consideration of the economic factor, we recommend port as a safe and an
      effective chemotherapy access for cancer patients, especially for whom needing
      long chemotherapy process.

PMID- 28744110
TI  - Confidence in correct inhaler technique and its association with treatment
      adherence and health status among US patients with chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Improper use of bronchodilators is associated with poor disease
      control, nonadherence to long-term therapy, and poor clinical outcomes. Our
      current understanding of factors associated with correct inhaler use and
      adherence is limited. We measured physician-and patient-reported confidence in
      device usage and associations with treatment adherence and COPD-related health
      status. METHODS: This was an analysis of a US observational, point-in-time survey
      of physicians and patients. Physicians who met study eligibility criteria
      completed surveys for 5 consecutive, eligible patients who were then invited to
      respond to questionnaires. We assessed patient demographics, type of prescribed
      inhaler device(s), device training, COPD severity, comorbidities, physician-and
      patient self-reported confidence in device usage, treatment adherence, and health
      status. RESULTS: Completed questionnaires for 373 patients were provided by 134
      physicians. Complete confidence in device usage was observed for 22% and 17% of
      patients as reported by patients and physicians, respectively. Greater confidence
      was associated with higher self-reported adherence to inhaler usage. Physicians
      were more likely than patients to report lower levels of patient confidence in
      device usage. High physician- and patient-reported confidence were associated
      with more favorable health status. Predictors of confidence in device usage
      included fewer comorbidities, no depression, and higher education levels.
      CONCLUSION: Low confidence in inhaler usage was associated with lower adherence
      and poor COPD-related health status. Choice of inhaler device tailored to
      patients' ability to use specific devices and ongoing education to support
      optimal inhaler usage may improve patient confidence and enhance both adherence
      and health status.

PMID- 28744111
TI  - The long-term effects of the health coaching self-management program for nursing
      home residents.
AB  - BACKGROUND AND AIMS: Little is known about whether a self-management program for
      nursing-home residents (NHR) with cognitive impairment is likely to have an
      impact on the care of this growing population. This study aimed to evaluate the
      effects of the health-coaching self-management program for NHR (HCSMP-NHR) on 1)
      self-efficacy and goal attainment scaling (GAS), 2) health status and quality of
      life (QoL) among older people, including those with cognitive impairment, in
      Korean nursing homes. METHODS: This was a cluster-randomized controlled trial.
      Participants in the intervention group (n=43, mean age =80.91+/-7.65 years)
      received the HCSMP-NHR intervention, composed of group health education and
      individual coaching, for 8 weeks. Conventional care was provided to the
      conventional group (n=47, mean age =80.19+/-7.53 years) during the same period.
      The effects of the HCSMP-NHR were measured three times: at baseline, week 9, and
      week 20. RESULTS: The intervention group showed better results for self-efficacy
      (P=0.007), health distress (P=0.007), depression (P<0.001), and QoL (P=0.04) at
      week 9. Mean GAS score of the intervention group gradually increased from -0.38
      to 0.74. The time * group interaction showed that the intervention group had
      significant improvements in QoL (P=0.047), and significant reductions in health
      distress (P=0.016) and depression (P<0.001), while showing no deterioration in
      shortness of breath (P<0.001). CONCLUSION: Our study findings indicate that the
      HCSMP-NHR improved self-efficacy and GAS and enhanced the health status and QoL
      of NHR with chronic conditions who also had mild-to-moderate cognitive
      impairment. Moreover, these effects were successfully maintained over the 5
      months of the trial. Further research is needed to establish the optimum
      intervention period and to assess the possibility of nationwide implementation of
      the HCSMP-NHR.

PMID- 28744112
TI  - Strontium ranelate treatment in a postmenopausal woman with osteonecrosis of the
      jaw after long-term oral bisphosphonate administration: a case report.
AB  - Bisphosphonates (BPs) suppress bone resorption and increase bone strength, thus
      reducing the risk of fracture. Oral BPs are widely used for the prevention and
      treatment of osteoporosis and osteopenia. Here, we describe the case of a
      postmenopausal woman who took oral alendronate for >3 years for osteoporosis. The
      patient presented at the clinic with sharp jaw pain and swelling on the left
      mandible 4 months after extraction of the third molar. Clinical examinations
      identified an inflamed mucosal opening with pus over an area of necrotic bone.
      Initial images of cone beam computed tomography revealed a sequestrum at the
      extracted socket. The condition did not improve after 1 week of antibiotic
      treatment; therefore, the alendronate treatment was terminated and the patient
      was prescribed strontium ranelate instead. The patient gradually recovered and,
      at the 2-year follow-up, the site of BP-related osteonecrosis of the jaw healed
      completely as determined by both clinical and cone beam computed tomography
      measures. The bone mineral densities in the femoral neck and lumbar spine
      improved after 1 year, and were maintained at the 3-year follow-up. The serum C
      terminal cross-linking telopeptide values also gradually increased from the
      initial 130 pg/mL to 320 pg/mL at the 3-year follow-up. Taken together, this case
      supports the use of strontium ranelate as an alternative treatment for
      postmenopausal women who receive long-term oral BP treatments and are at risk for
      serious complications of BP-related osteonecrosis of the jaw.

PMID- 28744113
TI  - Apolipoprotein epsilon7 allele in memory complaints: insights through protein
      structure prediction.
AB  - PURPOSE: APOE epsilon7 gene is a rare mutant form of APOE epsilon3. The mutation
      occurs in the lipid-binding domain of APOE. Based on the protein's structure,
      APOE epsilon7 is expected to function in lipid and beta-amyloid metabolism,
      similar to APOE epsilon4. However, unlike that for APOE epsilon4, the mechanisms
      responsible for Alzheimer's disease (AD) cases associated with APOE epsilon7
      expression have not been elucidated. The present study aims to investigate the
      association between APOE epsilon7 expression and cognitive impairment. METHODS:
      APOE was sequenced in DNA samples collected from 344 memory-complaint patients
      who visited the memory clinic, and from 345 non-memory-complaint individuals from
      the health promotion center. The protein structures of ApoE3, ApoE4, and ApoE7
      were predicted. RESULTS: Three epsilon3/epsilon7 heterozygote individuals who
      were all classified under the memory-complaint group were identified. Of these,
      two subjects were clinically diagnosed with AD with small vessel disease, and the
      remaining individual was diagnosed with subjective cognitive impairment. This
      study predicted the protein structures of ApoE3, ApoE4, and ApoE7 and determined
      the three-dimensional structure of the carboxy terminus of ApoE7, which
      participates in an electrostatic domain interaction similar to that of APOE
      epsilon4. APOE K244 or K245 mutations for APOE epsilon7 were not found in the
      Korean reference genome database, which contains information
      (http://152.99.75.168/KRGDB/browser/mainBrowser.jsp) from 622 healthy
      individuals. CONCLUSION: As verified by the results of structural prediction,
      APOE epsilon7 could serve as another risk factor for cognitive impairment and is
      particularly associated with vascular disease. However, additional studies are
      required to validate the pathogenic nature of APOE epsilon7.

PMID- 28744114
TI  - Acute effects of power and resistance exercises on hemodynamic measurements of
      older women.
AB  - PURPOSE: The purpose of this study was to compare the acute effects of resistance
      training (RT) and power training (PT) on the hemodynamic parameters and nitric
      oxide (NO) bioavailability of older women. MATERIALS AND METHODS: A randomized
      experimental design was used in this study. Twenty-one older women (age: 67.1+/
      4.6 years; body mass index: 28.03+/-4.9 kg/m2; systolic blood pressure: 135.1+/
      21.1 mmHg) were recruited to participate in this study. Volunteers were randomly
      allocated into PT, RT, and control session (CS) groups. The PT and RT groups
      underwent a single session of physical exercise equalized by training volume,
      characterized by 3 sets of 8-10 repetitions in 8 different exercises. However, RT
      group performed exercise at a higher intensity (difficult) than PT (moderate)
      group. On the other hand, concentric contractions were faster in PT group than in
      RT group. Hemodynamic parameters and saliva samples (for NO quantification) were
      collected before and during an hour after exercise completion. RESULTS: Results
      demonstrated post-exercise hypotension during 35 minutes in the PT when compared
      to rest period (P=0.001). In turn, RT showed decreased heart rate and double
      product (P<0.001) during the whole evaluation period after exercise completion
      compared with the rest period. NO levels increased in the PT and RT during the
      whole evaluation period in relation to rest period. However, there were no
      differences between PT, RT, and CS regarding hemodynamic and NO evaluations.
      CONCLUSION: Data indicate that an acute session of power and resistance exercise
      can be effective to cause beneficial changes on hemodynamic parameters and NO
      levels in older women.

PMID- 28744115
TI  - Bronchodilator efficacy of extrafine glycopyrronium bromide: the Glyco 2 study.
AB  - An extrafine formulation of the long-acting muscarinic antagonist glycopyrronium
      bromide (GB) is in development for chronic obstructive pulmonary disease (COPD),
      in combination with beclometasone dipropionate and formoterol fumarate - a "fixed
      triple". This two-part study was randomized, double blind, placebo controlled in
      patients with moderate-to-severe COPD: Part 1: single-dose escalation, GB 12.5,
      25, 50, 100 or 200 MUg versus placebo; Part 2: repeat-dose (7-day), four-period
      crossover, GB 12.5, 25 or 50 MUg twice daily (BID) versus placebo, with an open
      label extension in which all patients received tiotropium 18 MUg once daily. On
      the morning of Day 8 in all five periods, patients also received formoterol 12
      MUg. In study Part 1, 27 patients were recruited. All GB doses significantly
      increased from baseline forced expiratory volume in 1 second (FEV1) area under
      the curve (AUC0-12h) and peak FEV1, with a trend toward greater efficacy with
      higher GB dose. All adverse events were mild-moderate in severity, with a lower
      incidence with GB than placebo and no evidence of a dose-response relationship.
      In study Part 2, of 38 patients recruited, 34 completed the study. Adjusted mean
      differences from placebo in 12 h trough FEV1 on Day 7 (primary) were 115, 142 and
      136 mL for GB 12.5, 25 and 50 MUg BID, respectively (all P<0.001). GB 25 and 50
      MUg BID were superior (P<0.05) to GB 12.5 MUg BID for pre-dose morning FEV1 on
      Day 8. For this endpoint, GB 25 and 50 MUg BID were also superior to tiotropium.
      Compared with Day 7, addition of formoterol significantly increased Day 8 FEV1
      peak and AUC0-12h with all GB doses and placebo (all P<0.001). All adverse events
      were mild-moderate in severity and there was no indication of a dose-related
      relationship. This study provides initial evidence on bronchodilation, safety and
      pharmacokinetics of extrafine GB BID. Overall, the results suggest that GB 25 MUg
      BID is the optimal dose in patients with COPD.

PMID- 28744116
TI  - Tumor necrosis factor receptor 2 as a possible marker of COPD in smokers and ex
      smokers.
AB  - INTRODUCTION: Oxidative stress and systemic inflammation are higher in smokers
      and patients with COPD; however, markers that may help differentiate between
      smokers and patients with COPD have not yet been identified. We hypothesized that
      tumor necrosis factor-alpha receptor (TNFR) and soluble form of the receptor for
      advanced glycation end products (sRAGE) can be indicators of COPD in asymptomatic
      patients. PATIENTS AND METHODS: We evaluated 32 smokers (smoking history >10 pack
      years), 32 patients with mild/moderate COPD (smokers and ex-smokers), and 32
      never smokers. Concentrations of C-reactive protein (CRP), interleukin (IL)-6,
      TNFR1 and TNFR2, advanced glycation end products (AGEs), and the sRAGE were
      measured in serum. RESULTS: There were higher CRP and AGEs concentrations in
      smokers and in patients with COPD (P<0.001 and P=0.01, respectively) compared to
      controls, without statistical difference between smokers and patients with COPD.
      Concentrations of sRAGE, IL-6, and TNFR1 did not differ between study groups.
      TNFR2 was significantly higher in patients with COPD than in smokers (P=0.004)
      and controls (P=0.004), and the presence of COPD (P=0.02) and CRP (P=0.001)
      showed a positive association with TNFR2. Positive associations for smoking
      (P=0.04), CRP (P=0.03), and IL-6 (P=0.03) with AGEs were also found. The
      interaction variable (smoking * COPD) showed a positive association with IL-6.
      CONCLUSION: Our data suggest that TNFR2 may be a possible marker of COPD in
      asymptomatic smokers and ex-smokers. Although smokers and patients with early
      COPD presented other increased systemic inflammation markers (eg, CRP) and
      oxidative stress (measured by AGEs), they did not differentiate smokers from
      COPD.

PMID- 28744117
TI  - Alteration of the irisin-brain-derived neurotrophic factor axis contributes to
      disturbance of mood in COPD patients.
AB  - COPD is accompanied by limited physical activity, worse quality of life, and
      increased prevalence of depression. A possible link between COPD and depression
      may be irisin, a myokine, expression of which in the skeletal muscle and brain
      positively correlates with physical activity. Irisin enhances the synthesis of
      brain-derived neurotrophic factor (BDNF), a neurotrophin involved in reward
      related processes. Thus, we hypothesized that mood disturbances accompanying COPD
      are reflected by the changes in the irisin-BDNF axis. Case history, routine
      laboratory parameters, serum irisin and BDNF levels, pulmonary function, and
      disease-specific quality of life, measured by St George's Respiratory
      Questionnaire (SGRQ), were determined in a cohort of COPD patients (n=74). Simple
      and then multiple linear regression were used to evaluate the data. We found that
      mood disturbances are associated with lower serum irisin levels (SGRQ's Impacts
      score and reciprocal of irisin showed a strong positive association; beta:
      419.97; 95% confidence interval [CI]: 204.31, 635.63; P<0.001). This association
      was even stronger among patients in the lower 50% of BDNF levels (beta: 434.11;
      95% CI: 166.17, 702.05; P=0.002), while it became weaker for patients in the
      higher 50% of BDNF concentrations (beta: 373.49; 95% CI: -74.91, 821.88; P=0.1).
      These results suggest that irisin exerts beneficial effect on mood in COPD
      patients, possibly by inducing the expression of BDNF in brain areas associated
      with reward-related processes involved in by depression. Future interventional
      studies targeting the irisin-BDNF axis (eg, endurance training) are needed to
      further support this notion.

PMID- 28744118
TI  - Voluntary lung function screening to reveal new COPD cases in southern Italy.
AB  - BACKGROUND: Underdiagnosis of COPD is a relevant issue, and most frequently
      involves patients at early stages of the disease. Physicians do not routinely
      recommend smokers to undergo spirometry, unless they are symptomatic. AIMS: To
      investigate the effectiveness of voluntary lung function screening in bringing to
      light patients with previously unknown COPD and to evaluate the relationships
      among symptoms, smoking status, and airway obstruction. METHODS: A voluntary
      screening study for COPD was conducted during two editions of the annual Fiera
      del Levante (2014 and 2015), an international trade fair in Bari. Subjects were
      eligible for the study if they fulfilled the following inclusion criteria: age
      >=35 years, smoker/ex-smoker >=5 pack-years (PYs), or at least one chronic
      respiratory symptom (cough, sputum production, shortness of breath, and
      wheezing). A free post-beta2-agonist spirometry test was performed by trained
      physicians for each participant using portable spirometers. Post-beta2-agonist
      forced expiratory volume in 1 second (FEV1):forced vital capacity ratio <0.7 was
      chosen to establish the diagnosis of COPD. Sensitivity, specificity, and negative
      and positive predictive values (NPVs and PPVs) of symptoms for the presence of
      obstruction were calculated. RESULTS: A total of 1,920 individuals were eligible
      for the study; 188 subjects (9.8%) met COPD criteria. There was a 10.4%
      prevalence of COPD in subjects with one or more symptoms who had never smoked or
      smoked <=5 PYs. Among COPD patients, prevalence of symptoms increased in the
      presence of FEV1 <80%. COPD smokers were more symptomatic than smokers without
      COPD. Sensitivity and specificity in all subjects with one or more symptoms were
      87% and 32%, respectively, whereas in smoker subgroups, sensitivity and
      specificity were 71% and 41% (>=5 PYs) and 74% and 35% (>=10 PYs), respectively.
      In all subjects, the presence of at least one symptom was associated with a low
      PPV for COPD of 11%, but a very high NPV (96%). These data did not change if the
      analysis was limited to smokers. CONCLUSION: Voluntary public lung function
      screening programs in Italy are effective, and may detect a large number of
      undiagnosed subjects with COPD in early stages. In our population, COPD symptoms
      had low specificity and PPV, even considering smokers only.

PMID- 28744119
TI  - Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration
      after myocardial infarction.
AB  - The local, intramyocardial injection of proteins into the infarcted heart is an
      attractive option to initiate cardiac regeneration after myocardial infarction
      (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has
      been implicated as one of the most promising protein candidates in cardiac
      regeneration. A significant challenge to the therapeutic use of this protein is
      its short half-life in vivo. In this study, we evaluated the therapeutic effects
      and long-term retention of liraglutide loaded in poly(lactic-co-glycolic acid)
      poly(ethylene glycol) (PLGA-PEG) nanoparticles (NP-liraglutide) on experimental
      MI. PLGA-PEG nanoparticles (NPs) have been shown to efficiently load liraglutide
      and release bioactive liraglutide in a sustained manner. For in vitro test, the
      released liraglutide retained bioactivity, as measured by its ability to activate
      liraglutide signaling pathways. Next, we compared the effects of an
      intramyocardial injection of saline, empty NPs, free liraglutide and NP
      liraglutide in a rat model of MI. NPs were detected in the myocardium for up to 4
      weeks. More importantly, an intramyocardial injection of NP-liraglutide was
      sufficient to improve cardiac function (P<0.05), attenuate the infarct size
      (P<0.05), preserve wall thickness (P<0.05), promote angiogenesis (P<0.05) and
      prevent cardiomyocyte apoptosis (P<0.05) at 4 weeks after injection without
      affecting glucose levels. The local, controlled, intramyocardial delivery of NP
      liraglutide represents an effective and promising strategy for the treatment of
      MI.

PMID- 28744121
TI  - Design, optimization and characterization of coenzyme Q10- and D-panthenyl
      triacetate-loaded liposomes.
AB  - Coenzyme Q10 (CoQ10) is a lipid-soluble molecule found naturally in many
      eukaryotic cells and is essential for electron transport chain and energy
      generation in mitochondria. D-Panthenyl triacetate (PTA) is an oil-soluble
      derivative of D-panthenol, which is essential for coenzyme A synthesis in the
      epithelium. Liposomal formulations that encapsulate both ingredients were
      prepared and optimized by applying response surface methodology for increased
      stability and skin penetration. The optimum formulation comprised 4.17 mg CoQ10,
      4.22 mg PTA and 13.95 mg cholesterol per 100 mg of soy phosphatidylcholine. The
      encapsulation efficiency of the optimized formulation for CoQ10 and PTA was found
      to be 90.89%+/-3.61% and 87.84%+/-4.61%, respectively. Narrow size distribution
      was achieved with an average size of 161.6+/-3.6 nm, while a spherical and
      uniform shape was confirmed via scanning electron microscopy and transmission
      electron microscopy images. Cumulative release of 90.93% for PTA and 24.41% for
      CoQ10 was achieved after 24 hours of in vitro release study in sink conditions.
      Physical stability tests indicated that the optimized liposomes were suitable for
      storage at 4 degrees C for at least 60 days. The results suggest that the
      optimized liposomal formulation would be a promising delivery system for both
      ingredients in various topical applications.

PMID- 28744120
TI  - Inhibitory effect of a new orally active cedrol-loaded nanostructured lipid
      carrier on compound 48/80-induced mast cell degranulation and anaphylactic shock
      in mice.
AB  - BACKGROUND: Type I hypersensitivity is an allergic reaction characterized by the
      overactivity of the immune system provoked by normally harmless substances.
      Glucocorticoids, anti-histamines, or mast cell stabilizers are the choices of
      treatment for type I hypersensitivity. Even though these drugs have the anti
      allergic effect, they can have several side effects in prolong use. Cedrol is the
      main bioactive compound of Cedrus atlantica with anti-tumor, anti-oxidative, and
      platelet-activating factor inhibiting properties. METHODS: In this study, the
      preparation and anti-anaphylactic effect of cedrol-loaded nanostructured lipid
      carriers (NLCs) were evaluated. NLCs were prepared using Compritol(r) 888 ATO and
      triolein as lipid phase and vitamin E d-alpha-tocopherylpolyethyleneglycol 1000
      succinate, soya lecithin, and sodium deoxycholate as nanoparticle stabilizers.
      RESULTS: The average diameter of cedrol-NLCs (CR-NLCs) was 71.2 nm (NLC-C1) and
      91.93 nm (NLC-C2). The particle had negative zeta potential values of -31.9 mV
      (NLC-C1) and -44.5 mV (NLC-C2). Type I anaphylactoid reaction in the animal model
      is significantly reduced by cedrol and cedrol-NLC. This in vivo activity of
      cedrol resulted that cedrol suppressed compound 48/80-induced peritoneal mast
      cell degranulation and histamine release from mast cells. Furthermore, compound
      48/80-evoked Ca2+ uptake into mast cells was reduced in a dose-dependent manner
      by cedrol and cedrol-NLC. Studies confirmed that the inhibition of type I
      anaphylactoid response in vivo in mice and compound 48/80-induced mast cell
      activation in vitro are greatly enhanced by the loading of cedrol into the NLCs.
      The safety of cedrol and CR-NLC was evaluated as selectivity index (SI) with
      prednisolone and cromolyn sodium as positive control. SI of CR-NLC-C2 was found
      to be 11.5-fold greater than both prednisolone and cromolyn sodium. CONCLUSION:
      Administration of CR-NLC 24 hours before the onset of anaphylaxis can prevent an
      anaphylactoid reaction. NLCs could be a promising vehicle for the oral delivery
      of cedrol to protect anaphylactic reactions.

PMID- 28744122
TI  - Penetration of blood-brain barrier and antitumor activity and nerve repair in
      glioma by doxorubicin-loaded monosialoganglioside micelles system.
AB  - For the treatment of glioma and other central nervous system diseases, one of the
      biggest challenges is that most therapeutic drugs cannot be delivered to the
      brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study
      was to construct a nanodelivery vehicle system with capabilities to overcome the
      BBB for central nervous system administration. Doxorubicin as a model drug
      encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading
      efficiency and 97.05% encapsulation efficiency by orthogonal experimental design.
      The in vitro study demonstrated a slow and sustainable drug release in
      physiological conditions. In the cellular uptake studies, mixed micelles could
      effectively transport into both human umbilical vein endothelial cells and C6
      cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed
      micelles were accumulated sustainably and distributed centrally in the brain.
      Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the
      BBB and enter the brain. Among all the treatment groups, the median survival time
      of C6-bearing rats after administering DOX/GM1 micelles was significantly
      prolonged. In conclusion, the ganglioside nanomicelles developed in this work can
      not only penetrate BBB effectively but also repair nerves and kill tumor cells at
      the same time.

PMID- 28744123
TI  - Skeleton labeled 13C-carbon nanoparticles for the imaging and quantification in
      tumor drainage lymph nodes.
AB  - Carbon nanoparticles (CNPs) have been widely used in tumor drainage lymph node
      (TDLN) imaging, drug delivery, photothermal therapy, and so on. However, during
      the theranostic applications, the accumulation efficiency of CNPs in target
      organs is unknown yet, which largely hinders the extension of CNPs into clinical
      uses. Herein, we prepared skeleton-labeled 13C-CNPs that had identical properties
      to commercial CNPs suspension injection (CNSI) for the imaging and quantification
      in TDLN. 13C-CNPs were prepared by arc discharge method, followed by
      homogenization with polyvinylpyrrolidone. The size distribution and morphology of
      13C-CNPs were nearly the same as those of CNSI under transmission electron
      microscope. The hydrodynamic radii of both 13C-CNPs and CNSI were similar, too.
      According to X-ray photoelectron spectroscopy and infrared spectroscopy analyses,
      the chemical compositions and chemical states of elements were also nearly
      identical for both labeled and commercial forms. The skeleton labeling of 13C was
      reflected by the shift of G-band toward lower frequency in Raman spectra. 13C
      CNPs showed competitive performance in TDLN imaging, where the three lymph nodes
      (popliteal lymph node, common iliac artery lymph node, and paraaortic lymph node)
      were stained black upon the injection into the hind extremity of mice. The direct
      quantification of 13C-CNPs indicated that 877 MUg/g of 13C-CNPs accumulated in
      the first station of TDLN (popliteal lymph node). The second station of TDLN
      (common iliac artery lymph node) had even higher accumulation level (1,062
      MUg/g), suggesting that 13C-CNPs migrated efficiently along lymphatic vessel. The
      value decreased to 405 MUg/g in the third station of TDLN (paraaortic lymph
      node). Therefore, the 13C-CNPs provided quantitative approach to image and
      quantify CNSI in biological systems. The implication in biomedical applications
      and biosafety evaluations of CNSI is discussed.

PMID- 28744124
TI  - Fast-degrading PLA/ORMOGLASS fibrous composite scaffold leads to a calcium-rich
      angiogenic environment.
AB  - The success of scaffold implantation in acellular tissue engineering approaches
      relies on the ability of the material to interact properly with the biological
      environment. This behavior mainly depends on the design of the graft surface and,
      more precisely, on its capacity to biodegrade in a well-defined manner (nature of
      ions released, surface-to-volume ratio, dissolution profile of this release, rate
      of material resorption, and preservation of mechanical properties). The
      assessment of the biological behavior of temporary templates is therefore very
      important in tissue engineering, especially for composites, which usually exhibit
      complicated degradation behavior. Here, blended polylactic acid (PLA) calcium
      phosphate ORMOGLASS (organically modified glass) nanofibrous mats have been
      incubated up to 4 weeks in physiological simulated conditions, and their
      morphological, topographical, and chemical changes have been investigated. The
      results showed that a significant loss of inorganic phase occurred at the
      beginning of the immersion and the ORMOGLASS maintained a stable composition
      afterward throughout the degradation period. As a whole, the nanostructured
      scaffolds underwent fast and heterogeneous degradation. This study reveals that
      an angiogenic calcium-rich environment can be achieved through fast-degrading
      ORMOGLASS/PLA blended fibers, which seems to be an excellent alternative for
      guided bone regeneration.

PMID- 28744125
TI  - A top-down technique to improve the solubility and bioavailability of
      aceclofenac: in vitro and in vivo studies.
AB  - The aim of the present work was to tackle the solubility issue of a
      biopharmaceutics classification system (BCS)-II drug, aceclofenac. Although a
      number of attempts to increase the aqueous solubility have been made, none of the
      methods were taken up for scale-up. Hence size reduction technique by a top-down
      approach using wet milling process was utilized to improve the solubility and,
      consequently, the dissolution velocity of aceclofenac. The quality of the final
      product was ensured by Quality by Design approach wherein the effects of critical
      material attributes and critical process parameters were assessed on the critical
      quality attributes (CQAs) of nanocrystals. Box-Behnken design was applied to
      evaluate these effects on critical quality attributes. The optimized nanocrystals
      had a particle size of 484.7+/-54.12 nm with a polydispersity index (PDI) of
      0.108+/-0.009. The solid state characterization of the formulation revealed that
      the crystalline nature of the drug was slightly reduced after the milling
      process. With the reduced particle size, the solubility of the nanocrystals was
      found to increase in both water and 0.1 N HCl when compared with that of unmilled
      pure aceclofenac. These results were further supported by in vitro release
      studies of nanocrystals where an appreciable dissolution velocity with 100.07%+/
      2.38% release was observed for aceclofenac nanocrystals compared with 47.66%+/
      4.53% release for pure unmilled aceclofenac at the end of 2 h. The in vivo
      pharmacokinetic data generated showed a statistically significant increase in the
      Cmax for aceclofenac nanocrystals of 3.75+/-0.28 ug/mL (for pure unmilled
      aceclofenac Cmax was 1.96+/-0.17 ug/mL). The results obtained indicated that the
      developed nanocrystals of aceclofenac were successful in improving the
      solubility, thus the absorption and bioavailability of the drug. Hence, it may be
      a viable and cost-effective alternative to the current therapy.

PMID- 28744126
TI  - Gold nanoparticle-based miR155 antagonist macrophage delivery restores the
      cardiac function in ovariectomized diabetic mouse model.
AB  - Diabetic cardiomyopathy is a common disease in postmenopausal women, in whom the
      estrogen deficiency aggravates the pathology. In this study, we have found that
      estrogen deficiency due to ovariectomy aggravates the inflammation in the hearts
      of diabetic mice, as depicted by excessive proinflammatory type 1 macrophages
      (M1) over anti-inflammatory type 2 macrophages (M2). Accordingly, an additional
      increase of reactive oxygen species, cell apoptosis, cardiac hypertrophy, and
      fibrosis was observed in the hearts of ovariectomized diabetic mice, in
      comparison with the diabetes-only group. Significantly, miR155, a potent promoter
      of M1 polarization, was found to be additionally enhanced in the macrophages and
      hearts by ovariectomy. Tail vein injection of miR155-AuNP, in which thiol
      modified antago-miR155 was covalently conjugated with gold nanoparticle (AuNP),
      preferentially delivered the nucleic acids into the macrophages via phagocytosis.
      Together with the increased M2 ratio and reduced inflammation, in vivo delivery
      of antago-miR155 reduced cell apoptosis and restored the cardiac function. The
      restoration efficacy of miR155-AuNP was much better than general macrophage
      depletion by clodrosome. In summary, we revealed that M1/M2 imbalance contributes
      to the aggravated cardiomyopathy in ovariectomized diabetic mice, and
      therapeutically reducing miR155 in macrophages by AuNP serves as a promising
      strategy in improving cardiac function.

PMID- 28744127
TI  - Necrostatin-1 attenuates early brain injury after subarachnoid hemorrhage in rats
      by inhibiting necroptosis.
AB  - Necroptosis is programmed cell death that has been recently proposed and reported
      to be involved in several neurologic diseases. However, the role of necroptosis
      in early brain injury after subarachnoid hemorrhage (SAH) is still unknown. The
      purpose of this study was to investigate whether necroptosis was involved in SAH
      induced early brain injury, and to assess the possible neuroprotective effect of
      necrostatin-1 using an endovascular perforation rat model of SAH. Our results
      showed that the expression levels of necroptosis-related proteins including RIP1,
      RIP3 and MLKL in the basal cortex all increased at 3 hours after SAH (P<0.05) and
      peaked at 48 hours after SAH (P<0.05). However, they were greatly reduced after
      treatment with necrostatin-1 (P<0.05). Concurrently, neurologic outcomes were
      significantly improved after necrostatin-1 treatment (P<0.05). Furthermore, brain
      edema, blood-brain barrier disruption, necrotic cell death and neuroinflammation
      were also greatly inhibited after necrostatin-1 treatment. These results indicate
      that necroptosis is an important mechanism of cell death involved in the early
      brain injury after experimental SAH. Necrostatin-1 perhaps can serve as a
      promising neuroprotective agent for SAH treatment.

PMID- 28744128
TI  - A 6-year follow-up of children assessed for suspected autism spectrum disorder:
      parents' experiences of society's support.
AB  - BACKGROUND: Early support and interventions are suggested to be important for
      children with autism spectrum disorder (ASD) and other developmental problems and
      their families. Parents are described to have a burdensome life situation where
      the child's problems have a great impact on the family's well-being. AIM: To
      obtain increased knowledge of parents' experiences of support and interventions 6
      years after their child was assessed for ASD. METHODS AND PROCEDURES: A semi
      structured questionnaire was sent to all parents (n=101) whose preschool children
      (<4 years of age) had been assessed for ASD about 6 years prior in Gothenburg,
      Sweden. The open-ended questions were analyzed thematically using a hermeneutic
      phenomenological approach. OUTCOMES AND RESULTS: Parents of 56 children answered
      30 questions about their experiences concerning support from society after the
      neuropsychiatric assessment. From the eight open-ended questions, three themes
      were identified: parental responsibility, resources and competence among actors
      in society, and inequality. The parents experienced that they had to take
      responsibility for meeting the needs of and securing support for their child.
      They found that the support given was unequal, uncoordinated, and with great
      variations between both geographical areas and professionals. Parents' own
      resources were described as impacting the possibility to secure adequate
      interventions, resulting in unequal treatment of families depending on
      socioeconomic status. Several parents also expressed experiencing a lack of
      individualization of services and interventions. All children had received some
      kind of action from society, but not to the degree they had wished for when the
      children got their ASD diagnosis. CONCLUSION AND IMPLICATIONS: The essence of
      parents' comments was the experience of authorities and societal actors trying to
      push the responsibility onto someone else. The study indicates a need for
      continuous longitudinal support for children identified with neurodevelopmental
      problems before the age of 3 years. This requires collaboration and coordination
      between different societal bodies.

PMID- 28744129
TI  - Sleep disturbances among patients with epilepsy.
AB  - AIM: The aim of this study was to analyze the prevalence of sleep disorders among
      patients with epilepsy and to compare the incidence of sleep disorders between
      the clinical and demographics factors. MATERIALS AND METHODS: The study was
      conducted among 302 patients with epilepsy. Sleep disturbances were measured with
      the Polish version of the Pittsburgh Sleep Quality Questionnaire (PSQI). The
      questionnaire prepared and applied by the authors contained questions relating to
      sociodemographic characteristics, clinical status, and sleep. RESULTS AND
      CONCLUSION: Mean PSQI score in the study group was 9+/-2 points, with the range
      of 4-16 points. PSQI test results were analyzed with regard to clinical and
      demographic characteristics of those suffering from epilepsy: gender, age,
      profession, body mass index, illness duration, number of medicines taken, type of
      seizures, frequency of seizures, time which elapsed since last seizure,
      provocative factor of seizure attacks, occurrence of adverse effects of
      antiepileptic drugs (AEDs). Furthermore, the existence of a relationship between
      PSQI test result and particular sleep-related factors or particular sleep
      conditions was examined. However, the examination of a relationship between
      certain independent variables and the final PSQI test result did not prove the
      existence of a statistically relevant influence (in all cases P>0.05).

PMID- 28744130
TI  - Long noncoding RNA CASC2 predicts the prognosis of glioma patients and functions
      as a suppressor for gliomas by suppressing Wnt/beta-catenin signaling pathway.
AB  - BACKGROUND: Previous studies have demonstrated that long noncoding RNA cancer
      susceptibility candidate 2 (lncRNA CASC2) is frequently downregulated in several
      types of tumors and functions as a tumor-suppressive factor. However, the
      clinical significance and function of CASC2 in human glioma remain largely
      unknown. The purpose of this study was to identify the clinical values of CASC2,
      as well as investigate the potential molecular mechanisms in glioma. METHODS:
      This retrospective study first analyzed the expression levels of CASC2 using
      quantitative real-time polymerase chain reaction. Then, CASC2 expression levels
      were associated with various clinicopathologic characteristics and the survival
      rate of patients with glioma. Finally, the function and underlying molecular
      mechanisms of CASC2 in human glioma were investigated in U251 cell line. RESULTS:
      By quantitative real-time polymerase chain reaction analysis, our data showed
      that CASC2 expression was significantly downregulated in glioma tissues and cell
      lines (U87 and U251) compared to adjacent normal brain tissues or normal human
      astrocytes. Moreover, its expression negatively correlated with tumor grade in
      glioma patients. Furthermore, Kaplan-Meier curves with log-rank analysis revealed
      a close correlation between downregulated CASC2 and shorter survival time in
      glioma patients. In addition, Cox regression analysis indicated that CASC2 could
      be considered as an independent risk factor for poor prognosis. Finally, in vitro
      experiment demonstrated that CASC2 overexpression remarkably suppressed glioma
      cell proliferation, migration, and invasion through suppressing Wnt/beta-catenin
      signaling pathway. CONCLUSION: This study suggested that CASC2 may potentially
      serve as a valuable diagnostic and prognostic biomarker and a therapeutic target
      for glioma patients.

PMID- 28744131
TI  - Long-acting formulations delivering aripiprazole: beyond single-value
      characterizations of steady-state pharmacokinetics.

PMID- 28744132
TI  - The most important psychological and psychosocial needs of Polish multiple
      sclerosis patients and their significant others.
AB  - BACKGROUND: People with multiple sclerosis (MS) and their relatives often have
      multiple, complex needs which require support from a wide range of services. The
      aim of the study, the first of its kind in Poland, was to identify the most
      important needs of patients with MS and their significant others (SO). METHODS: A
      questionnaire developed from focus groups consisting of 20 needs-related
      statements was administered in seven MS centers to 573 MS patients and 220 SO.
      The mean age of the patients was 42.61 years old; the mean MS duration was 9.43
      years. The respondents were asked to rate the needs statements according to their
      importance on an 11-point scale. The questionnaire was similar for the MS
      patients and their SO. RESULTS: The most important needs in the patient group
      were: to feel needed and efficient in life; to have easy access to professional
      rehabilitation; and to be sure that doctors are interested in my condition. The
      three most important needs in the SO group were: to know that relatives/friends
      feel needed and efficient in life; to have good living conditions; and to be sure
      that doctors are interested in my relative's/friend's condition. Correlation
      analysis revealed that in the patients group, there was a positive correlation
      between patient's age and the importance of factors such as the need for support
      and interest in their disease from the family doctor (P<0.004), receiving
      educational materials from an MS clinic (P<0.011), interest from the clinic in
      life issues of the patient (P<0.001), and the need for access to self
      rehabilitation (P<0.003); while the need to continue working part-time was
      inversely correlated with age (P<0.009). CONCLUSION: The needs of the MS patients
      and SO were similar. The data validate the importance of interdisciplinary care
      for the MS population.

PMID- 28744133
TI  - Real-time functional magnetic resonance imaging in obsessive-compulsive disorder.
AB  - The current literature provides substantial evidence of brain alterations
      associated with obsessive-compulsive disorder (OCD) symptoms (eg, checking,
      cleaning/decontamination, counting compulsions; harm or sexual,
      symmetry/exactness obsessions), and emotional problems (eg, defensive/appetitive
      emotional imbalance, disgust, guilt, shame, and fear learning/extinction) and
      cognitive impairments associated with this disorder (eg, inhibitory control,
      working memory, cognitive flexibility). Building on this evidence, new clinical
      trials can now target specific brain regions/networks. Real-time functional
      magnetic resonance imaging (rtfMRI) was introduced as a new therapeutic tool for
      the self-regulation of brain-mind. In this review, we describe initial trials
      testing the use of rtfMRI to target brain regions associated with specific OCD
      symptoms (eg, contamination), and other mind-brain processes (eg, cognitive -
      working memory, inhibitory control, emotional - defensive, appetitive systems,
      fear reduction through counter-conditioning) found impaired in OCD patients.
      While this is a novel topic of research, initial evidence shows the promise of
      using rtfMRI in training the self-regulation of brain regions and mental
      processes associated with OCD. Additionally, studies with healthy populations
      have shown that individuals can regulate brain regions associated with cognitive
      and emotional processes found impaired in OCD. After the initial "proof-of
      concept" stage, there is a need to follow up with controlled clinical trials that
      could test rtfMRI innovative treatments targeting brain regions and networks
      associated with different OCD symptoms and cognitive-emotional impairments.

PMID- 28744134
TI  - Reconstruction of fingers after electrical injury using lateral tarsal artery
      flap.
AB  - OBJECTIVE: Electrical injuries to the fingers account for the majority of total
      severe burns that occur each year. While several types of flaps have been used in
      covering finger defects, all have limitations or disadvantages. The purpose of
      this study was to introduce our clinical experiences of using the lateral tarsal
      artery (LTA) flap to successfully restore fingers after electrical injury.
      PATIENTS AND METHODS: From 2005 to 2012, 10 patients with 14 severe electrical
      burns to their fingers, including six thumbs and four index and four middle
      fingers, were treated with LTA flap. The wound size ranged from 2.0*3.0 cm to
      3.5*5.0 cm. The flap with free tendon graft was used to repair the tendon defect
      in four cases, free nerve graft was used to repair the feeling defect in two
      cases, and the flap with nerve was used to repair the feeling defect in two
      cases. All the patients were followed up for 3 months to 2 years. RESULTS: All
      skin flaps adhered successfully and there were no complications. All patients
      were satisfied with the esthetic appearance and functional outcome of the finger
      reconstruction. CONCLUSION: LTA flap is a reliable method to restore fingers
      after severe electrical injuries.

PMID- 28744135
TI  - Sex differences of in-hospital outcome and long-term mortality in patients with
      Takotsubo cardiomyopathy.
AB  - BACKGROUND: Previous studies revealed that patients with Takotsubo cardiomyopathy
      (TTC) have a higher mortality rate than the general population. It is still
      unclear whether sex differences may influence long-term prognosis of TTC
      patients. The purpose of this study was to determine whether sex differences do
      influence the short- and long-term outcomes of TTC. METHODS AND RESULTS: A total
      of 114 patients with TTC were admitted to the University Medical Centre Mannheim
      from January 2003 to September 2015 and entered into the TTC database of the
      University Medical Centre Mannheim, and retrospectively analyzed. Patients were
      diagnosed by the Mayo Clinic criteria. All-cause mortality over mean follow-up of
      1,529+/-1,121 days was revealed. Significantly more male patients died within
      long-term follow-up compared to female TTC patients (log-rank test; P=0.01). Most
      males died of noncardiac causes. In multivariate Cox regression analysis, the
      male sex (P=0.02, hazard ratio [HR] 2.8, 95% CI 1.1-7.2), the ejection fraction
      <=35% (P=0.01, HR 3.3, 95% CI 1.2-9.2) and glomerular filtration rate <60 mL/min
      (P<0.01, HR 3.1, 95% CI 1.4-7.0) figured out as independent predictors of the
      adverse outcome. CONCLUSION: This study shows that males suffering from TTC
      reveal a higher long-term all-cause mortality rate than females over a 5 year
      follow-up period.

PMID- 28744136
TI  - Quick reference guide to apixaban.
AB  - Direct oral anticoagulants (DOACs) are being increasingly used in the clinical
      setting for patients at risk of venous thromboembolism (VTE) and/or stroke. These
      medications offer valued benefits for long-term use, including a fast onset of
      anticoagulation, fixed anticoagulation profile (and consequent prescription of
      specified doses) and no requirement for routine monitoring. Apixaban is a
      selective factor Xa inhibitor, approved for use in the prevention of stroke in
      patients with nonvalvular atrial fibrillation and in the prevention and treatment
      of acute VTE. Like many of the DOACs, it has a fast onset of action and works to
      deliver predictable coagulation results. Multiple randomized controlled trials
      including ARISTOTLE and AMPLIFY have shown apixaban to be noninferior to vitamin
      K antagonists in the prevention of stroke and VTE, with a good safety profile.
      This article aims to review the use of apixaban for the prevention and treatment
      of thromboembolic disease, highlighting the key study results that have led to
      its current licensing and use.

PMID- 28744137
TI  - Polypeptide N-acetylgalactosaminyltransferase-6 expression in gastric cancer.
AB  - Gastric cancer (GC) is one of the leading causes of cancer-related deaths, with
      limited improvement in its clinical outcome worldwide. Aberrant mucin-type O
      glycosylation is a critical event widespread in the development of GC.
      Polypeptide N-acetylgalactosaminyltransferases (GALNTs) regulate the initial step
      and determine the sites of mucin-type O-glycoprotein bio-synthesis. GALNT6 has
      considerable potential as a biomarker in various cancers. The roles of GALNT6 in
      GC were analyzed, and the results showed that GALNT6 expression markedly
      increased in GC tissues compared with those in adjacent gastric tissues. High
      intratumoral GALNT6 density was associated with the clinicopathological
      parameters of TNM stage and distant metastasis. GALNT6 was identified as an
      independent prognosticator for the poor prognosis of GC patients. Moreover, the
      high expression level of GALNT6 was significantly associated with the low
      expression levels of E-cadherin and beta-catenin and the high expression levels
      of MMP9. These findings indicated that GALNT6 could provide new insights into the
      characterization of GC as well as contribute to the development of an efficient
      prognostic indicator and novel therapeutic modalities for GC.

PMID- 28744138
TI  - Preoperative serum carcinoembryonic antigen levels are associated with histologic
      subtype, EGFR mutations, and ALK fusion in patients with completely resected lung
      adenocarcinoma.
AB  - BACKGROUND: Serum carcinoembryonic antigen (CEA) is often elevated in lung
      adenocarcinoma, but not in all patients. Meanwhile, epidermal growth factor
      receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusion protein are
      the main driving forces in lung adenocarcinoma. However, whether CEA levels are
      associated with histologic subtype, EGFR mutations, and ALK fusion remain largely
      unclear. METHODS: Preoperative serum CEA levels, postoperative histologic
      subtypes, and statuses of EGFR mutations and ALK fusion protein were
      retrospectively assessed in 442 patients with completely resected lung
      adenocarcinoma treated from January 2014 to December 2015 at Zhejiang Cancer
      Hospital, People's Republic of China. RESULTS: EGFR mutations were found in 69.9%
      (309/442) of lung adenocarcinoma patients, and ALK fusion protein in 4.5%
      (20/442). EGFR mutations occurred more frequently in the lepidic subtype
      (P=0.001). High preoperative serum CEA levels (CEA >20 ng/mL) were independently
      associated with EGFR mutations (P<0.001). Moreover, in patients with CEA levels
      of 21-49 ng/mL, the EGFR mutation rate was 88.2%, which was higher compared to
      those obtained in the other subgroups. In addition, all specimens were invasive
      adenocarcinoma, with lepidic (18.6%), papillary (15.4%), acinar (52.7%), solid
      (9.7%), micropapillary (3.2%), and mucinous predominant (0.4%) subtypes; CEA
      levels in patients with the solid subtype were higher than those of other
      histologic subtypes (P=0.001). CONCLUSION: Preoperative serum CEA levels can
      serve as a reference marker to identify the histologic subtype, and EGFR mutation
      or ALK fusion protein status, in lung adenocarcinoma patients. Moreover,
      histological subtypes could also predict EGFR mutations.

PMID- 28744139
TI  - The long noncoding RNA, TINCR, functions as a competing endogenous RNA to
      regulate PDK1 expression by sponging miR-375 in gastric cancer.
AB  - BACKGROUND: Accumulating evidence indicates that the long noncoding RNA, TINCR,
      plays a critical role in cancer progression and metastasis. However, the overall
      biological role and mechanisms of TINCR that were involved in human gastric
      cancer (GC) progression remain largely unknown. METHODS: TINCR expression was
      measured in 56 paired tumor and adjacent nontumor tissue samples by real-time
      polymerase chain reaction (PCR). Insights of the mechanism of competitive
      endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase
      assays. The effects of TINCR and miR-375 on GC cell apoptosis and proliferation
      were studied by RNA interference approaches in vitro and in vivo. The correlation
      of TINCR and PDK1 was identified by real-time PCR and Western blot analysis.
      RESULTS: Our results showed that miR-375 level decreased and TINCR level
      increased in tumor tissues. In addition, TINCR was a target of miR-375 and
      inhibited its expression in GC cells. Furthermore, the low expression of TINCR
      increased cell apoptosis and inhibited the proliferation of GC cells, while the
      downregulation of miR-375 reversed the function. In particular, TINCR could
      negatively regulate the miR-375 expression and increased the PDK1 expression in
      GC cells. Finally, tumor growth suppression was retarded with miR-375
      downregulated in TINCR knockdown of GC cell xenografts. CONCLUSION: The long
      noncoding RNA TINCR functions as a competing endogenous RNA to regulate PDK1
      expression by sponging miR-375 in GC. The ceRNA regulatory network of TINCR/miR
      375/PDK1 allows us to better understand the pathogenesis of GC and facilitate the
      development of long noncoding RNA (lncRNA)-directed diagnostics in GC.

PMID- 28744140
TI  - Emerging treatments for HER2-positive early-stage breast cancer: focus on
      neratinib.
AB  - Over the last decades, a better understanding of breast cancer heterogeneity
      provided tools for a biologically based personalization of anticancer treatments.
      In particular, the overexpression of the human epidermal growth factor receptor 2
      (HER2) by tumor cells provided a specific target in these HER2-positive tumors.
      The development of the monoclonal antibody trastuzumab, and its approval in 1998
      for the treatment of patients with metastatic disease, radically changed the
      natural history of this aggressive subtype of breast cancer. These findings
      provided strong support for the continuous research in targeting the HER2 pathway
      and implementing the development of new anti-HER2 targeted agents. Besides
      trastuzumab, a series of other anti-HER2 agents have been developed and are
      currently being explored for the treatment of breast cancer patients, including
      those diagnosed with early-stage disease. Among these agents, neratinib, an oral
      tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the
      intracellular level, has shown promising results, including when administered to
      patients previously exposed to trastuzumab-based treatment. This article aims to
      review the available data on the role of the HER2 pathway in breast cancer and on
      the different targeted agents that have been studied or are currently under
      development for the treatment of patients with early-stage HER2-positive disease
      with a particular focus on neratinib.

PMID- 28744141
TI  - The translational expression of ABCA2 and ABCA3 is a strong prognostic biomarker
      for multidrug resistance in pediatric acute lymphoblastic leukemia.
AB  - PURPOSE: The aim of this work was to study the correlation between the
      expressions of the ABCA2 and ABCA3 genes at the mRNA and protein levels in
      children with acute lymphoblastic leukemia (ALL) and the effects of this
      association on multidrug resistance (MDR). MATERIALS AND METHODS: Sixty-nine
      children with de novo ALL and 25 controls were enrolled in the study. Mononuclear
      cells were isolated from the bone marrow. The mRNA levels of ABCA2 and ABCA3 were
      measured by real-time polymerase chain reaction (PCR). Samples with high mRNA
      levels were assessed for respective protein levels by Western blotting. Following
      the first year of treatment, persistent monoclonality of T-cell gamma receptors
      or immunoglobulin H (IgH) gene rearrangement was assessed and considered as the
      MDR. The tertiary structure of ABCA2 was predicted using Phyre2 and I-TASSER web
      systems and compared to that of ABCA3, which has been previously reported.
      Molecular docking was performed using DOCK 6.7. RESULTS: Real-time quantitative
      PCR (qRT-PCR) showed high levels of ABCA2 and ABCA3 mRNAs in 13 and 17 samples,
      respectively. Among them, five and eight individuals demonstrated high levels of
      ABCA2 and ABCA3, respectively. Response to chemotherapy was significantly
      decreased (P=0.001) when the mRNA and protein of both genes were overexpressed
      compared to individuals with high transcriptional levels of either ABCA2 or ABCA3
      alone. Close similarity between ABCA2 and ABCA3 structures was revealed by
      protein tertiary structure prediction, whereas molecular docking analysis
      suggested similar binding of chemotherapy drugs and therefore a potentially
      similar role in determining the MDR. CONCLUSION: Our findings suggested, for the
      first time, that quantification of the protein level of ABCA2 and ABCA3
      transporters had a prognostic impact on pediatric ALL MDR. Furthermore, the
      tertiary structure of ABCA2 was predicted for the first time, and docking
      analysis revealed a possible compensatory effect between ABCA2 and ABCA3
      transporters, which may contribute to the efflux of cytotoxic drugs and,
      ultimately, to chemoresistance.

PMID- 28744142
TI  - Sex-related differences in clinicopathological features and survival of patients
      with primary urethral carcinoma: a population-based study.
AB  - PURPOSE: To analyze the Surveillance, Epidemiology, and End Results (SEER)
      database to determine the effects of sex and prognostic factors on the survival
      of patients with primary urethral carcinoma (PUC). MATERIALS AND METHODS: We
      selected 453 patients diagnosed with PUC from 2004 to 2013 from the SEER
      database. Statistical analysis was used to identify sex-specific differences
      associated with tumor characteristics and cancer-specific survival (CSS) and
      overall survival (OS). RESULTS: Compared with men, there was a higher proportion
      of black women, more negative lymph-node status, higher American Joint Committee
      on Cancer (AJCC) stage, more advanced T3 stage, more with adenocarcinoma (Ac),
      and fewer with squamous cell carcinoma (SCC) or transitional cell carcinoma
      (TCC). Among women, black race and M1 stage were associated with shorter CSS and
      OS, respectively. In addition, surgery was associated with longer OS in women.
      Among men, AJCC III and IV and M1 stages were associated with shorter CSS and OS.
      In addition, age >75 years associated with shorter OS in men. CONCLUSION: Black
      race was associated with shorter OS and CSS of women, and surgery was associated
      with longer OS of women. Among men, AJCC stage III and IV were associated with
      shorter OS and CSS. Age >75 years was associated with shorter OS in men only.
      Women with Ac experienced poor CSS compared with men. Men with TCC experienced
      worse CSS compared with those with Ac or SCC.

PMID- 28744143
TI  - Prognostic role of lymphocyte to monocyte ratio for patients with pancreatic
      cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Lymphocyte to monocyte ratio (LMR) was recently reported as a
      prognostic factor of pancreatic cancer (PC). However, the prognostic role of LMR
      in PC remains inconsistent and inconclusive. The aim of this study was to assess
      the prognostic value of LMR in patients with PC through meta-analysis. METHODS:
      Eligible studies inquiring into the connection between LMR and survival of
      patients with PC were collected and extracted by searching PubMed, Embase,
      Cochrane Library and Web of Science up to May 9, 2017. Pooled hazard ratios (HRs)
      and the 95% CIs were calculated to assess the prognostic value of LMR on overall
      survival (OS) and disease-free survival/recurrence-free survival/time to
      progression (DFS/RFS/TTP). RESULTS: A total of 1,795 patients with PC from 8
      studies were included in the meta-analysis. Pooled analysis indicated that
      elevated LMR predicted a favorable OS (HR =0.56, 95% CI: 0.38-0.83, P=0.004) and
      DFS/RFS/TTP in PC patients (HR =0.38, 95% CI: 0.15-0.95, P=0.04). Prognostic
      values of LMR on OS were observed in subgroups with all ethnicities, treatment
      with surgery, American Joint Committee on Cancer (AJCC) stage of III-IV, and LMR
      cut-off value >=3. In addition, low LMR was significantly connected with gender
      and AJCC stage. CONCLUSION: An elevated LMR is associated with favorable survival
      in patients with pancreatic cancer.

PMID- 28744144
TI  - ALK and ROS1 concurrent with EGFR mutation in patients with lung adenocarcinoma.
AB  - PURPOSE: The purpose of this study was to explore the frequencies of ALK and ROS1
      fusion genes in EGFR-mutant lung adenocarcinoma patients and examine the
      therapeutic efficacies of EGFR-tyrosine kinase inhibitors (TKIs). MATERIALS AND
      METHODS: A total of 421 EGFR-mutated patients taking EGFR-TKIs were examined for
      ALK and ROS1 fusion genes based on reverse transcription-polymerase chain
      reaction (RT-PCR). Progression-free survival (PFS) and overall survival (OS) were
      evaluated by the Kaplan-Meier method and compared by the log-rank test. RESULTS:
      The mutations of ALK rearrangement (n=10) and ROS1 rearrangement (n=3) were
      detected. All the patients received EGFR-TKIs, and eight took subsequent ALK/ROS1
      inhibitor. PFS was longer in single EGFR mutants (n=408) than in EGFR/ALK or
      EGFR/ROS1 counterparts (n=13; 10.7 vs 6.6 months, P=0.004). No difference in OS
      existed between single EGFR and EGFR/ALK or EGFR/ROS1 mutants (21.0 vs 23.0
      months, P=0.196). The median PFS of eight patients treated with ALK/ROS1
      inhibitor was 6.0 months. CONCLUSION: Concomitant ALK/ROS1 fusion genes occurred
      in 3.1% EGFR-mutated lung adenocarcinoma patients. Concomitant ALK/ROS1-EGFR
      mutations may influence the therapeutic efficacy of EGFR-TKIs.

PMID- 28744145
TI  - A comprehensive insight into the clinicopathologic significance of miR-144-3p in
      hepatocellular carcinoma.
AB  - BACKGROUND: Studies which focused on the character of miR-144-3p in
      hepatocellular carcinoma (HCC) are limited. This study aimed to explore the
      expression, clinical significance and the potential targets of miR-144-3p in HCC.
      METHODS: The Cancer Genome Atlas (TCGA) and a cohort of 95 cases of HCC were
      applied to investigate aberrant miR-144-3p expression in HCC. A meta-analysis was
      performed to accumulate data on miR-144-3p expression in HCC based on TCGA,
      quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Gene
      Expression Omnibus (GEO). Additionally, the potential regulatory mechanisms of
      miR-144-3p in HCC were explored by bioinformatics. RESULTS: MiR-144-3p expression
      was downregulated distinctly in HCC compared to para-HCC tissue both in TCGA data
      (8.9139+/-1.5986 vs 10.7721+/-0.9156, P<0.001) and in our qRT-PCR validation
      (1.3208+/-0.7594 vs 2.6200+/-0.9263, P<0.001). The meta-analysis based on TCGA,
      qRT-PCR and GEO data confirmed a consistent result (standard mean difference =
      0.854, 95% CI: -1.224 to -0.484, P<0.001). The receiver operating characteristic
      curve of miR-144-3p gained a significant diagnostic value both in TCGA data (area
      under the curve [AUC] =0.852, 95% CI: 0.810 to 0.894, P<0.001) and in qRT-PCR
      validation (AUC =0.867, 95% CI: 0.817 to 0.916, P<0.001), especially in alpha
      fetoprotein-negative HCC patients (AUC =0.900, 95% CI: 0.839 to 0.960, P<0.001).
      Furthermore, we identified 119 potential targets of miR-144-3p in HCC by
      bioinformatics. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway
      analyses revealed that several significant biologic functions and pathways
      correlated with the pathogenesis of HCC, including the p53 signaling pathway.
      CONCLUSION: MiR-144-3p may function as a cancer suppressor microRNA, which is
      essential for HCC progression through the regulation of various signaling
      pathways. Thus, interactions with miR-144-3p may provide a novel treatment
      strategy for HCC in the future.

PMID- 28744146
TI  - RNA sequencing identifies gene expression profile changes associated with beta
      estradiol treatment in U2OS osteosarcoma cells.
AB  - This study was conducted to identify gene expression profile changes associated
      with beta-estradiol (E2) treatment in U2OS osteosarcoma cells by high-throughput
      RNA sequencing (RNA-seq). Two U2OS cell samples treated with E2 (15 MUmol/L) and
      two untreated control U2OS cell samples were subjected to RNA-seq. Differentially
      expressed genes (DEGs) between the groups were identified, and main biological
      process enrichment was performed using gene ontology (GO) analysis. A protein
      protein interaction (PPI) network was constructed using Cytoscape based on the
      Human Protein Reference Database. Finally, NFKB1 expression was confirmed by
      quantitative real-time polymerase chain reaction (qRT-PCR). The map ratios of the
      four sequenced samples were >65%. In total, 128 upregulated and 92 downregulated
      DEGs were identified in E2 samples. After GO enrichment, the downregulated DEGs,
      such as AKT1, were found to be mainly enriched in cell cycle processes, whereas
      the upregulated DEGs, such as NFKB1, were involved in the regulation of gene
      expression. Moreover, AKT1 (degree =117) and NFKB1 (degree =72) were key nodes
      with the highest degrees in the PPI network. Similarly, the results of qRT-PCR
      confirmed that E2 upregulated NFKB1 expression. The results suggest that E2
      upregulates the expression of NFKB1, ATF7IP, and HDAC5, all of which are involved
      in the regulation of gene expression and transcription, but downregulates that of
      TCF7L2, ALCAM, and AKT, which are involved in Wnt receptor signaling through beta
      catenin and morphogenesis in U2OS osteosarcoma cells.

PMID- 28744147
TI  - Evaluation of p53 gene expression and prognosis characteristics in uveal melanoma
      cases.
AB  - OBJECTIVE: The objective of this study was to evaluate the correlation between
      the expression of p53 gene and the prognosis after local excision in uveal
      melanoma. MATERIALS AND METHODS: Real-time polymerase chain reaction (RT-PCR)
      test and Western blot were used to detect the expression of p53 in C918, MUM-2B,
      and D78 cell lines at the levels of messenger RNA (mRNA) and protein.
      Immunohistochemistry staining was done in the tissues of 68 patients, which were
      diagnosed with uveal melanoma. Furthermore, the effects of p53 protein on the
      invasion abilities of both the cell lines were studied by transinfection of p53
      small interfering RNA. The clinical and prognostic data regarding the effect of
      p53 protein on the patient's prognosis were calculated and further analyzed by
      Kaplan-Meier univariate analysis method. RESULTS: The results of RT-PCR and
      Western blot revealed that p53 mRNAs were highly expressed in C918 and MUM-2B
      cells. The high expression rate of p53 among the 88 uveal melanoma tissues was
      77.27%. Transinfection of p53 serine could inhibit the expression of p53 in uveal
      melanoma and the invasion ability of the cells. This study found that the high
      expression of p53 and the prognosis of uveal melanoma patients were statistically
      correlated. CONCLUSION: The expression of p53 protein in uveal melanoma was
      unusual and was associated with the invasion ability of uveal melanoma. This
      indicates that the highest expression of p53 protein indicates worse prognosis of
      uveal melanoma patients.

PMID- 28744149
TI  - Determinants of multidrug-resistant tuberculosis in Addis Ababa, Ethiopia.
AB  - Multidrug-resistant tuberculosis (MDR-TB) has been jeopardizing the global effort
      to prevent and control tuberculosis (TB). However, data on MDR-TB in Ethiopia in
      general, and in our study area in particular, are very scarce. The aim of this
      study was to identify determinants of MDR-TB in a cohort of patients managed in
      two referral hospitals of Addis Ababa, Ethiopia, between April 1, 2013 and June
      30, 2013. A health facility-based case-control study was conducted. A total of
      710 TB patients (229 confirmed MDR-TB and 481 drug susceptible TB patients) were
      enrolled in this study. Identified independent determinants for MDR-TB were
      contact history with a known TB patient (adjusted odds ratio [AOR]: 1.9, 95% CI:
      1.1-3.3), previous history of TB treatment (AOR: 11.9, 95% CI: 6.8-21), history
      of hospitalization (AOR: 4.4 95% CI: 2.2-7.8), sputum-smear positivity (AOR: 1.9,
      95% CI: 1.1-3.4), and social stigma (AOR: 5.1, 95% CI: 1.8-14.4). These
      identified factors should be considered for use in MDR-TB screening tool
      development if universal drug susceptibility testing is not possible. Moreover,
      TB infection control practices in health care settings should be further
      strengthened. As factors may vary from region to region, further broader studies
      need to be conducted in other parts of Ethiopia.

PMID- 28744148
TI  - Recent progress on the effects of microRNAs and natural products on tumor
      epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) is a biological process of phenotypic
      transition of epithelial cells that can promote physiological development as well
      as tissue healing and repair. In recent years, cancer researchers have noted that
      EMT is closely related to the occurrence and development of tumors. When tumor
      cells undergo EMT, they can develop enhanced migration and local tissue invasion
      abilities, which can lead to metastatic growth. Nevertheless, two researches in
      NATURE deny its necessity in specific tumors and that is discussed in this
      review. The degree of EMT and the detection of EMT-associated marker molecules
      can also be used to judge the risk of metastasis and to evaluate patients'
      prognosis. MicroRNAs (miRNAs) are noncoding small RNAs, which can inhibit gene
      expression and protein translation through specific binding with the 3'
      untranslated region of mRNA. In this review, we summarize the miRNAs that are
      reported to influence EMT through transcription factors such as ZEB, SNAIL, and
      TWIST, as well as some natural products that regulate EMT in tumors. Moreover,
      mutual inhibition occurs between some transcription factors and miRNAs, and these
      effects appear to occur in a complex regulatory network. Thus, understanding the
      role of miRNAs in EMT and tumor growth may lead to new treatments for
      malignancies. Natural products can also be combined with conventional
      chemotherapy to enhance curative effects.

PMID- 28744150
TI  - Radiofrequency ablation using Barrx(r) for the endoscopic treatment of gastric
      antral vascular ectasia: a series of three cases and a review of the literature
      on treatment options.
AB  - Gastric antral vascular ectasia (GAVE), also known as "watermelon stomach", is an
      uncommon condition, which can cause gastrointestinal bleeding due to rupture of
      blood vessels that line the stomach. The pathogenesis of GAVE remains unclear;
      however it is thought that hemodynamic changes, mechanical stress, and autoimmune
      factors all have a part to play. A range of conditions are also commonly
      associated with the syndrome, such as portal hypertensive gastropathy, liver
      cirrhosis, and autoimmune disorders. Less commonly, chronic renal failure,
      cardiac diseases, and bone marrow transplantation have coexisted with GAVE. The
      diagnosis is usually based on visualization of the tissue upon endoscopy;
      however, histology plays a role in uncertain cases. The typical "watermelon"
      appearance relates to the tissue having a striped appearance radiating out from
      the pylorus. Medical treatment has failed to show satisfactory results and
      surgery is usually considered as a last resort, due to its increased risk for
      complications and mortality. Lasers and argon plasma coagulation have been used
      recently, and been shown to be as effective as surgery and a safer option. We
      present three cases of gastric antral vascular ectasia treated at our institution
      with radiofrequency ablation and review the literature on treatment modalities
      for GAVE.

PMID- 28744151
TI  - Is it possible to preserve the blood supply of erectile organs by anastomosis
      using the hypogastric artery in kidney transplantation?
AB  - INTRODUCTION: Three modalities for treating chronic kidney failure are peritoneal
      dialysis, hemodialysis, and kidney transplantation. Among them kidney
      transplantation is cost-efficient and leads to a somewhat normal quality of life.
      In this approach, most often the external iliac artery is selected for
      anastomosis, but this could be disastrous if anastomosis leads to a complication.
      The traditional end-to-end approach for anastomosis of the kidney artery to the
      internal iliac artery leads to pelvic organ ischemia. However, if the end-to-end
      anastomosis is replaced by an end-to-side approach, it is safer. This report
      discusses some cases of end-to-side anastomosis using the internal iliac artery.
      METHOD: In ten cases of chronic kidney failure, we anastomosed the kidney artery
      to the internal iliac artery with an end-to-side approach. RESULTS: After vessels
      were unclamped, all patients had diuresis. Their creatinine was in normal range
      and was blood flow in the internal iliac artery, based on color Doppler
      ultrasound. CONCLUSION: End-to-side anastomosis can be done in some chronic
      kidney failure patients if their internal iliac arteries are large enough. This
      approach is safer than anastomosis using the external iliac artery.

PMID- 28744152
TI  - Pharmacodynamic genetic polymorphisms affect adverse drug reactions of
      haloperidol in patients with alcohol-use disorder.
AB  - BACKGROUND: Antipsychotic action of haloperidol is due to blockade of D2
      receptors in the mesolimbic dopamine pathway, while the adverse drug reactions
      are associated with striatal D2 receptor blockade. Contradictory data concerning
      the effects of genetic polymorphisms of genes encoding these receptors and
      associated structures (catechol-O-methyltransferase [COMT], glycine transporter
      and gene encoding the density of D2 receptors on the neuronal membrane) are
      described. OBJECTIVE: The objectives of this study were to evaluate the
      correlation between DRD2, SLC6A3 (DAT) and COMT genetic polymorphisms and to
      investigate their effect on the development of adverse drug reactions in patients
      with alcohol-use disorder who received haloperidol. PATIENTS AND METHODS: The
      study included 64 male patients (average age 41.38 +/- 10.14 years, median age 40
      years, lower quintile [LQ] 35 years, upper quintile [UQ] 49 years). Bio-Rad CFX
      ManagerTM software and "SNP-Screen" sets of "Syntol" (Russia) were used to
      determine polymorphisms rs4680, rs1800497, rs1124493, rs2242592, rs2298826 and
      rs2863170. In every "SNP-Screen" set, two allele-specific hybridizations were
      used, which allowed to determine two alleles of studied polymorphism separately
      on two fluorescence channels. RESULTS: Results of this study detected a
      statistically significant difference in the adverse drug reaction intensity in
      patients receiving haloperidol with genotypes 9/10 and 10/10 of polymorphic
      marker SLC6A3 rs28363170. In patients receiving haloperidol in tablets, the
      increases in the UKU Side-Effect Rating Scale (UKU) score of 9.96 +/- 2.24
      (10/10) versus 13 +/- 2.37 (9/10; p < 0.001) and in the Simpson-Angus Scale (SAS)
      score of 5.04 +/- 1.59 (10/10) versus 6.41 +/- 1.33 (9/10; p = 0.006) were
      revealed. CONCLUSION: Polymorphism of the SCL6A3 gene can affect the safety of
      haloperidol, and this should be taken into account during the choice of drug and
      its dosage regimen.

PMID- 28744153
TI  - Assessment of sputum smear-positive but culture-negative results among newly
      diagnosed pulmonary tuberculosis patients in Tanzania.
AB  - Diagnosis of pulmonary tuberculosis (TB) in technology-limited countries is
      widely achieved by smear microscopy, which has limited sensitivity and
      specificity. The frequency and clinical implication of smear-positive but culture
      negative among presumptive TB patients remains unclear. A cross-sectional
      substudy was conducted which aimed to identify the proportion of nontuberculous
      mycobacteria (NTM) infections among 94 "smear-positive culture-negative" patients
      diagnosed between January 2013 and June 2016 in selected health facilities in
      Tanzania. Out of 94 sputa, 25 (26.60%) were GeneXpert(r) mycobacteria TB positive
      and 11/94 (11.70%) repeat-culture positive; 5 were Capilia TB-Neo positive and
      confirmed by GenoType MTBC to be Mycobacterium tuberculosis/Mycobacterium
      canettii. The remaining 6 Capilia TB-Neo negative samples were genotyped by
      GenoType(r) CM/AS, identifying 3 (3.19%) NTM, 2 Gram positive bacteria, and 1
      isolate testing negative, together, making a total of 6/94 (6.38%) confirmed
      false smear-positives. Twenty-eight (29.79%) were confirmed TB cases, while 60
      (63.83%) remained unconfirmed cases. Out of 6 (6.38%) patients who were HIV
      positive, 2 patients were possibly coinfected with mycobacteria. The isolation of
      NTM and other bacteria among smear-positive culture-negative samples and the
      presence of over two third of unconfirmed TB cases emphasize the need of both
      advanced differential TB diagnostic techniques and good clinical laboratory
      practices to avoid unnecessary administration of anti-TB drugs.

PMID- 28744154
TI  - Relationships between components of emotional intelligence and physical pain in
      alcohol-dependent patients.
AB  - PURPOSE: Chronic pain is a significant comorbidity in individuals with alcohol
      dependence (AD). Emotional processing deficits are a substantial component of
      both AD and chronic pain. The aim of this study was to analyze the interrelations
      between components of emotional intelligence and self-reported pain severity in
      AD patients. PATIENTS AND METHODS: A sample of 103 participants was recruited
      from an alcohol treatment center in Warsaw, Poland. Information concerning pain
      level in the last 4 weeks, demographics, severity of current anxiety and
      depressive symptoms, as well as neuroticism was obtained. The study sample was
      divided into "mild or no pain" and "moderate or greater pain" groups. RESULTS: In
      the logistic regression model, across a set of sociodemographic, psychological,
      and clinical factors, higher emotion regulation and higher education predicted
      lower severity, whereas increased levels of anxiety predicted higher severity of
      self-reported pain during the previous 4 weeks. When the mediation models looking
      at the association between current severity of anxiety and depressive symptoms
      and pain severity with the mediating role of emotion regulation were tested,
      emotion regulation appeared to fully mediate the relationship between depression
      severity and pain, and partially the relationship between anxiety severity and
      pain. CONCLUSION: The current findings extend previous results indicating that
      emotion regulation deficits are related to self-reported pain in AD subjects.
      Comprehensive strategies focusing on the improvement of mood regulation skills
      might be effective in the treatment of AD patients with comorbid pain symptoms.

PMID- 28744155
TI  - Efficacy of single-injection unilateral thoracic paravertebral block for post
      open cholecystectomy pain relief: a prospective randomized study at Gondar
      University Hospital.
AB  - BACKGROUND: Cholecystectomy can be associated with considerable postoperative
      pain. While the benefits of paravertebral block (PVB) on pain after thoracotomy
      and mastectomy have been demonstrated, not enough investigations on the effects
      of PVB on pain after open cholecystectomy have been conducted. We tested the
      hypothesis that a single-injection thoracic PVB reduces pain scores, decreases
      opioid consumption, and prolongs analgesic request time after cholecystectomy.
      METHODS: Of 52 patients recruited, 50 completed the study. They were randomly
      allocated into two groups: the paravertebral group and the control group. The
      outcome measures were the severity of pain measured on numeric pain rating scale,
      total opioid consumption, and first analgesic request time during the first
      postoperative 24 hours. RESULT: The main outcomes recorded during 24 hours after
      surgery were Numerical Rating Scale (NRS) pain scores (NRS, 0-10), cumulative
      opioid consumption, and the first analgesic request time. Twenty four hours after
      surgery, NRS at rest was 4 (3-6) vs 5 (5-7) and at movement 4 (4-7) vs 6 (5-7.5)
      for the PVB and control groups, respectively. The difference between the groups
      over the whole observation period was statistically significant (P<0.05). Twenty
      four hours after surgery, median (25th-75th percentile) cumulative morphine
      consumption was 0 (0-2) vs 2.5 (2-4) mg (P<0.0001) and cumulative tramadol
      consumption was 200 (150-250) mg vs 300 (200-350) mg in the paravertebral and in
      the control group, respectively (P=0.003). After surgery, the median (25th-75th
      percentile) first analgesic requirement time was prolonged in the PVB group in
      statistically significant fashion (P<0.0001). CONCLUSION AND RECOMMENDATIONS:
      Single-shot thoracic PVB as a component of multi-modal analgesic regimen provided
      superior analgesia when compared with the control group up to 24 postoperative
      hours after cholecystectomy, and we recommend this block for post cholecystectomy
      pain relief.

PMID- 28744156
TI  - Cholesterol biosynthesis inhibitor RO 48-8071 reduces progesterone receptor
      expression and inhibits progestin-dependent stem cell-like cell growth in hormone
      dependent human breast cancer cells.
AB  - Clinical trials and studies have shown that postmenopausal women undergoing
      combination hormone replacement therapy containing estrogen and progestin have an
      increased risk of breast cancer compared with women taking estrogen or placebo
      alone. Using animal models, we have previously shown that synthetic progestins,
      including medroxyprogesterone acetate (MPA), which is widely used clinically,
      accelerate breast cancer tumor growth and promote metastasis. Furthermore, we
      have found that MPA elevates CD44 protein expression and aldehyde dehydrogenase
      (ALDH) activity, two markers of cancer stem cells (CSCs), and increases
      mammosphere formation, another hallmark of stem cells, in hormone-dependent T47-D
      human breast cancer cells. Herein, we show that RO 48-8071 (RO), an inhibitor of
      cholesterol synthesis, reduced MPA-induced CD44 protein expression in two hormone
      dependent human breast cancer cell lines, T47-D and BT-474. Because we have
      previously shown that MPA induction of CD44 is progesterone receptor (PR)
      dependent, we examined RO's effects on PR protein and mRNA expressions in T47-D
      cells. PR mRNA levels remained unchanged after RO treatment; however, RO
      significantly reduced the protein expression of both PR receptor isoforms, PR-A
      and PR-B. Using the proteasome inhibitor MG-132, we demonstrated that RO
      decreases PR protein expression in T47-D cells via the proteasomal degradation
      pathway. Importantly, treatment of T47-D cells with RO abolished MPA-induced
      mammosphere formation. Based on our observations, we contend that RO may
      represent a novel means of preventing MPA-induced CSC expansion. RO could be used
      clinically to both treat and prevent hormone-dependent breast cancers, which
      represent the majority of human breast cancers. RO may also have clinical utility
      in reducing resistance to antihormone therapy.

PMID- 28744158
TI  - Estrogen-mediated hemangioma-derived stem cells through estrogen receptor-alpha
      for infantile hemangioma.
AB  - BACKGROUND: Infantile hemangiomas (IHs) are the most common benign vascular tumor
      of infancy. They occur more frequently in female infants. The cause of hemangioma
      is currently unknown; however, current studies suggested the importance of
      estrogen (E2) signaling in hemangioma proliferation. METHODS: Hemangioma-derived
      stem cells (HemSCs) were cultured with estrogen for 48-72 h; the cell viability
      and proliferation were evaluated with the messenger RNA (mRNA) and protein
      expression levels of fibroblast growth factor 2 (FGF2), vascular endothelial
      growth factor-A (VEGF-A) and estrogen receptor-alpha (ER-alpha), by application
      of several in vitro assays, such as methyl thiazolyl tetrazolium (MTT), reverse
      transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme-linked
      immunosorbent assay (ELISA) and Western blotting. Also, the cell population's
      response to external estrogen was investigated by in vivo experiments. HemSCs and
      human umbilical vein endothelial cells (HUVECs) were mixed and injected
      subcutaneously into 20 flank of BALB/c-nu mice, which were randomly divided into
      5 groups based on different E2 treatment doses (0, 0.01, 0.1 and 1 mg,
      respectively), 0.1 mg dimethyl sulfoxide (DMSO) as control. Each group of mice
      were treated intramuscularly every week, then 2 and 4 weeks later, the
      subcutaneous implants were harvested and evaluated the tumor tissues with
      microvessel density (MVD) assay and immunohistochemistry. RESULTS: The study
      demonstrated that application of E2 increased the expression of FGF2, VEGF-A, and
      ER-alpha in HemSCs with the optimal concentration from 10-9 to 10-5 M. Two-week
      treatment of E2 promoted expression of VEGF-A and FGF2 in HemSCs culture.
      Morphological, histological and immunohistological improvements were observed in
      vivo using murine IH model in which HemSCs and HUVECs were implanted into BALB/c
      nu mice that were post-injected with E2. In the grafts, mean MVD was markedly
      increased. CONCLUSION: The results suggested that E2 promotes angiogenesis via
      combination with ER-alpha to up-regulate the expression of VEGF-A in HemSCs,
      promoting proliferation of IHs. These findings provide critical insight into the
      potential mechanisms of E2 action on IHs.

PMID- 28744159
TI  - Induction regimens for transplant-eligible patients with newly diagnosed multiple
      myeloma: a network meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The aim of this study was to compare the early efficacy and survivals
      of induction regimens for transplant-eligible patients with untreated multiple
      myeloma. MATERIALS AND METHODS: A comprehensive literature search in electronic
      databases was conducted for relevant randomized controlled trials (RCTs).
      Eligible studies were selected according to the predefined selection criteria,
      before they were evaluated for methodological quality. Basic characteristics and
      data for network meta-analysis (NMA) were extracted from included trials and
      pooled in our meta-analysis. The end points were the overall response rate (ORR),
      progression-free survival (PFS), and overall survival (OS). RESULTS: A total of
      14 RCTs that included 4,763 patients were analyzed. The post-induction ORR was
      higher with bortezomib plus thalidomide plus dexamethasone (VTD) regimens, and
      VTD was better than the majority of other regimens. For OS, VTD plus
      cyclophosphamide (VTDC) regimens showed potential superiority over other
      regimens, but the difference was not statistically significant. The PFS was
      longer with thalidomide plus doxorubicin plus dexamethasone (TAD) regimens for
      transplant-eligible patients with newly diagnosed multiple myeloma (NDMM).
      CONCLUSION: The NMA demonstrated that the VTD, VTDC, and TAD regimens are most
      beneficial in terms of ORR, OS, and PFS for transplant-eligible patients with
      NDMM, respectively.

PMID- 28744157
TI  - The ABC7 regimen: a new approach to metastatic breast cancer using seven common
      drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine
      efficacy.
AB  - Breast cancer metastatic to bone has a poor prognosis despite recent advances in
      our understanding of the biology of both bone and breast cancer. This article
      presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment
      using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat
      aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination
      of breast cancer to bone. As add-on to current standard treatment with
      capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer
      treatment drugs to stop both the natural EMT process inherent to breast cancer
      and the added EMT occurring as a response to current treatment modalities.
      Chemotherapy, radiation, and surgery provoke EMT in cancer generally and in
      breast cancer specifically. ABC7 uses standard doses of capecitabine as used in
      treating breast cancer today. In addition, ABC7 uses 1) an older psychiatric
      drug, quetiapine, to block RANK signaling; 2) pirfenidone, an anti-fibrosis drug
      to block TGF-beta signaling; 3) rifabutin, an antibiotic to block beta-catenin
      signaling; 4) metformin, a first-line antidiabetic drug to stimulate AMPK and
      inhibit mammalian target of rapamycin, (mTOR); 5) propranolol, a beta-blocker to
      block beta-adrenergic signaling; 6) agomelatine, a melatonergic antidepressant to
      stimulate M1 and M2 melatonergic receptors; and 7) ribavirin, an antiviral drug
      to prevent eIF4E phosphorylation. All these block the signaling pathways - RANK,
      TGF-beta, mTOR, beta-adrenergic receptors, and phosphorylated eIF4E - that have
      been shown to trigger EMT and enhance breast cancer growth and so are worthwhile
      targets to inhibit. Agonism at MT1 and MT2 melatonergic receptors has been shown
      to inhibit both breast cancer EMT and growth. This ensemble was designed to be
      safe and augment capecitabine efficacy. Given the expected outcome of metastatic
      breast cancer as it stands today, ABC7 warrants a cautious trial.

PMID- 28744160
TI  - Impact of abiraterone on patient-related outcomes in metastatic castration
      resistant prostate cancer: current perspectives.
AB  - Abiraterone acetate has established a major role in the treatment paradigm of
      metastatic castration-resistant prostate cancer ever since pivotal trials, COU-AA
      301 and COU-AA-302, have shown benefit in both the second-line and first-line
      (post- and pre-chemotherapy) setting, respectively, with improvement in overall
      survival as well as secondary end points such as prostate-specific antigen (PSA)
      and radiographic response rates, time to PSA progression, and progression-free
      survival. There has been a lot of interest and emphasis in the evaluation of
      patient-related outcomes (PROs) as it relates to quality of life, pain, adverse
      events, fatigue, and among others, in the use of different agents that have been
      shown to improve survival. This review examines the companion PROs in conjunction
      with abiraterone acetate use. This is particularly relevant since PROs are
      increasingly viewed as a key metric for drug label claims in granting approval
      across regulatory agencies, including the US Food and Drug Administration and the
      European Medicines Agency.

PMID- 28744161
TI  - Emerging combination therapies for the management of multiple myeloma: the role
      of elotuzumab.
AB  - Treatment options for patients with multiple myeloma (MM) have increased during
      the past decade. Despite the significant advances, challenges remain on which
      combination strategies will provide the optimal response for any given patient.
      Defining optimal combination strategies and corresponding companion diagnostics,
      that will guide clinical decisions are required to target relapsed or refractory
      multiple myeloma (RRMM) in order to improve disease progression, survival and
      quality of life for patients with MM. Elotuzumab is a humanized monoclonal
      antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7),
      approved by the US Food and Drug Administration (FDA) in 2015 and the European
      Medicines Agency in 2016 for the treatment of MM. SLAMF7 is expressed in normal
      and malignant plasma cells and has lower expression on natural killer (NK) cells.
      Experimental evidence indicates that elotuzumab exhibits anti-myeloma activity
      through 1) antibody-dependent cell-mediated cytotoxicity, 2) enhancing NK cells
      cytotoxicity and 3) interfering with adhesion of MM cells to bone marrow stem
      cells (BMSCs). Although elotuzumab has no single agent activity in patients with
      RRMM who have received one to three prior therapies, the combination of
      elotuzumab with anti-myeloma agents, such as immunomodulatory drugs-lenalidomide,
      or proteasome inhibitors (PIs)-bortezomib, remarkably improved the overall
      response rates and progression-free survival in MM patients with only minimal
      incremental toxicity. In brief, the clinical data for elotuzumab indicate that
      targeting SLAMF7 in combination with the use of conventional therapies is
      feasible and effective with a tolerable safety profile for the treatment of RRMM.

PMID- 28744162
TI  - Validity of an automated algorithm using diagnosis and procedure codes to
      identify decompensated cirrhosis using electronic health records.
AB  - Viral hepatitis-induced cirrhosis can progress to decompensated cirrhosis.
      Clinical decompensation represents a milestone event for the patient with
      cirrhosis, yet there remains uncertainty regarding precisely how to define this
      important phenomenon. With the development of broader treatment options for
      cirrhotic hepatitis patients, efficient identification of liver status before
      evolving to decompensated cirrhosis could be life-saving, but research on the
      topic has been limited by inconsistencies across studies, populations, and case
      confirmation methods. We sought to determine whether diagnosis/procedure codes
      drawn from electronic health records (EHRs) could be used to identify patients
      with decompensated cirrhosis. In our first step, chart review was used to
      determine liver status (compensated cirrhosis, decompensated cirrhosis, non
      cirrhotic) in patients from the Chronic Hepatitis Cohort Study. Next, a hybrid
      approach between Least Absolute Shrinkage and Selection Operator regression and
      Classification Regression Trees models was used to optimize EHR-based
      identification of decompensated cirrhosis, based on 41 diagnosis and procedure
      codes. These models were validated using tenfold cross-validation; method
      accuracy was evaluated by positive predictive values (PPVs) and area under
      receiver operating characteristic (AUROC) curves. Among 296 patients (23 with
      hepatitis B, 268 with hepatitis C, and 5 co-infected) with a 2:1 ratio of biopsy
      confirmed cirrhosis to noncirrhosis, chart review identified 127 cases of
      decompensated cirrhosis (Kappa=0.88). The algorithm of five liver-related
      conditions-liver transplant, hepatocellular carcinoma, esophageal varices
      complications/procedures, ascites, and cirrhosis-yielded a PPV of 85% and an
      AUROC of 92%. A hierarchical subset of three conditions (hepatocellular
      carcinoma, ascites, and esophageal varices) demonstrated a PPV of 81% and an
      AUROC of 86%. Given the excellent predictive ability of our model, this EHR-based
      automated algorithm may be used to successfully identify patients with
      decompensated cirrhosis. This algorithm may contribute to timely identification
      and treatment of viral hepatitis patients who have progressed to decompensated
      cirrhosis.

PMID- 28744163
TI  - Cesarean section after abdominal mesh repair for pregnancy-related desmoid tumor:
      a case report.
AB  - We report the case of a 32-year-old gravida 2 para 1 woman with a background of
      partially resected desmoid tumor (DT) arising from the previous cesarean section
      (CS) scar. This case details the management of her DT by surgical resection and
      mesh repair and second pregnancy following this. Pregnancy-related DTs are a
      relatively rare entity, and there is a paucity of literature regarding their
      management during pregnancy. There are only five reported cases of DTs arising
      from CS scars. To our knowledge, this is the only report to illustrate that
      subsequent CS is possible after desmoid resection and abdominal mesh repair. It
      provides evidence that CS can be safely accomplished following abdominal wall
      reconstructions and further arguments against elective lower segment CS.

PMID- 28744164
TI  - Phenytoin-induced Stevens-Johnson syndrome with myocarditis: a rare case report.
AB  - Stevens-Johnson syndrome (SJS) is an acute life-threatening mucocutaneous
      reaction caused by excessive necrosis and detachment of the epidermis. It is
      commonly drug induced and phenytoin is a common precipitant. Phenytoin, an
      antiepileptic drug, is also known to cause myocarditis. Phenytoin causing both
      myocarditis and SJS in the same patient is very rare and can lead to increased
      morbidity and mortality. Here, we describe the case of a 43-year-old male who
      developed SJS and myocarditis secondary to phenytoin. In spite of aggressive
      resuscitative efforts, the patient could not be revived. Thus, a combination of
      myocarditis with SJS increases the mortality and should be considered in patients
      with SJS secondary to phenytoin and associated shock.

PMID- 28744165
TI  - Asymptomatic multinodular splenoma (splenic hamartoma) in a child with sickle
      cell anemia.
AB  - Splenoma is a rare and benign malformation usually fortuitously diagnosed during
      imaging, surgery or, unfortunately, at autopsy. Although splenoma was first
      described in 1861, its association with hematological pathology is a very unusual
      condition in children. We report the case of an asymptomatic splenoma in an 8
      year-old boy with sickle cell anemia, whose diagnosis was confirmed after
      conventional splenectomy.

PMID- 28744166
TI  - Intramyocellular lipids of muscle type in athletes of different sport
      disciplines.
AB  - The present study used magnetic resonance spectroscopy (1H-MRS) to examine
      quantitative differences in intramyocellular lipid (IMCL) contents in various
      muscle types at rest for individual athletes from different sport disciplines.
      Five groups consisting of sprinters, alpine skiers, cross-country skiers,
      endurance runners and untrained healthy male subjects volunteered for this study.
      Data were acquired using 1H-MRS from the tibialis anterior (TA), medial
      gastrocnemius (MG) and soleus (SOL) muscles. No significant difference was found
      in the cross-sectional area (CSA) of the TA, MG and SOL muscles, whereas the CSA
      of subcutaneous fat was significantly lower (p<0.01) for each athlete group
      compared with untrained subjects. In both TA and MG, IMCL concentrations in
      endurance runners were significantly higher than those of alpine skiers (p<0.01),
      sprinters (p<0.01) and untrained subjects (p<0.05). The IMCL concentrations in TA
      and MG of cross-country skiers were significantly higher than those of alpine
      skiers (p<0.05) and sprinters (TA, p<0.01; MG, p<0.05). There was no significant
      difference in the IMCL concentrations of TA and MG between alpine skiers or
      sprinters and untrained subjects. The IMCL concentration in SOL was significantly
      greater in endurance runners and showed no difference in cross-country skiers
      compared with that in alpine skiers and sprinters. There was no significant
      difference in the IMCL concentration of SOL between athletes and untrained
      subjects. These results suggest that differences in IMCL contents stored in
      various muscle types for athletes at rest are associated with the muscle cellular
      adaptation for differences in the type of exercise training and/or muscle fiber
      composition.

PMID- 28744167
TI  - Muckle-Wells syndrome: clinical perspectives.
AB  - Muckle-Wells syndrome (MWS) is a rare autoinflammatory disorder. It is due to
      NLRP3 gene mutations, responsible for excessive caspase-1 activation and
      interleukin 1beta processing. MWS is the intermediate phenotype of severity of
      cryopyrin-associated periodic syndrome. Urticarial rash, conjunctivitis,
      recurrent fever, arthralgia, and fatigue are the main clinical manifestations of
      MWS. Yet, sensorineural hearing loss and renal amyloidosis can occur after long
      term evolution. Patients' quality of life has been drastically improved with the
      advent of IL-1 inhibitors. This review reports recent findings in MWS,
      particularly genotype/phenotype correlation, and discusses the clinical
      perspectives of this disease in a time of efficient treatment.

PMID- 28744168
TI  - Spotlight on ramucirumab in the treatment of nonsmall cell lung cancer: design,
      development, and clinical activity.
AB  - The vascular endothelial growth factor (VEGF) and receptor is a therapeutic
      target because of the importance of this pathway in carcinogenesis. This pathway
      regulates and promotes angiogenesis as well as increases endothelial cell
      proliferation, permeability, and cancer survival. Ramucirumab is a new fully
      human monoclonal antibody that targets the VEGF receptor-2, an important key
      receptor implicated in angiogenesis. Ramucirumab has been approved for the
      treatment of second-line advanced or metastatic non-small cell lung cancer
      (NSCLC) in combination with the chemotherapy agent docetaxel. This was based on
      the result of the randomized trial REVEL of 1,253 patients with metastatic NSCLC
      previously treated with a platinum-based combination therapy. The authors
      observed a significant improvement in overall survival (OS) with an acceptable
      toxicities profile. In this study, patients were randomized to receive
      ramucirumab plus docetaxel or placebo with docetaxel. The combination of
      docetaxel and ramucirumab showed an improved OS (hazard ratio [HR]: 0.86; 95% CI:
      0.75, 0.98). Median OS was 10.5 months in the ramucirumab arm versus 9.1 months
      in the placebo arm. Regarding side effects, the toxicity described on the
      ramucirumab arm were principally diarrhea, fatigue, and neutropenia. The most
      common (5%) adverse reactions of grade 3 and 4 in the ramucirumab arm were
      fatigue, neutropenia, febrile neutropenia, leukopenia, and hypertension. Adding
      ramucirumab to docetaxel improves QoL of patients, and does not impair symptoms
      or functioning. There are currently several trials in progress evaluating the
      effects of ramucirumab in combination with other drugs in patients with advanced
      NSCLC.

PMID- 28744169
TI  - Residents-as-teachers across graduate medical education - expanding into the
      undergraduate medical curriculum.

PMID- 28744170
TI  - Improvement of seed shattering and dormancy in Oryza sativa L. 'Hokuriku 193'
      based on genetic information.
AB  - In this study, we investigated the genetic basis of seed shattering and dormancy
      in Hokuriku 193 and bred an NIL improved these traits. Analysis of an F3
      population from Hokuriku 193 * Koshihikari revealed a general correspondence
      between seed shattering and genotypes at the qSH1 locus, suggesting a strong
      influence of this locus on the seed shattering in Hokuriku 193. An F2 population
      from [ms-bo] Nekken 2 * Hokuriku 193 was also analyzed to identify quantitative
      trait loci (QTLs) for seed dormancy as measured by germination rate in the first
      December and March after seed harvest. The results revealed a concurrence QTLs of
      on chromosomes 1, 3, and 6 (qSDo1, qSDo3, qSDo6). In particular, qSDo1 and qSDo6
      were considered regions worthy of active modification because they were QTL
      regions that promoted seed dormancy when carrying Hokuriku 193 genome regions
      around. SSDo_NIL, a near isogenic line (NIL) derived from Hokuriku 193 by
      introgressing Nekken 2 alleles only at the qSH1 locus and qSDo1, did not shatter,
      and its germination rate was significantly higher than that of Hokuriku 193.
      Yield performance was similar between SSDo_NIL and Hokuriku 193, suggesting that
      improvement of seed shattering and dormancy does not affect yield.

PMID- 28744171
TI  - Genetic variation of root angle distribution in rice (Oryza sativa L.) seedlings.
AB  - We developed a new method of using seedling trays to evaluate root angle
      distribution in rice (Oryza sativa. L), and found a wide genetic variation among
      cultivars. The seedling tray method can be used to evaluate in detail the growth
      angles of rice crown roots at the seedling stage by allocating nine scores (10
      degrees  to 90 degrees ). Unlike basket methods, it can handle large plant
      populations over a short growth period (only 14 days). By using the method, we
      characterized the root angle distributions of 97 accessions into two cluster
      groups: A and B. The numbers of accessions in group A were limited, and these
      were categorized as shallow rooting types including soil-surface root. Group B
      included from shallow to deep rooting types; both included Indica and Japonica
      Group cultivars, lowland and upland cultivars, and landraces and improved types.
      No relationship between variation in root vertical angle and total root number
      was found. The variation in root angle distribution was not related to
      differentiation between the Japonica and Indica Groups, among ecosystems used for
      rice cultivation, or among degrees of genetic improvement. The new evaluation
      method and associated information on genetic variation of rice accessions will be
      useful in root architecture breeding of rice.

PMID- 28744172
TI  - Identification of quantitative trait loci for rice grain quality and yield
      related traits in two closely related Oryza sativa L. subsp. japonica cultivars
      grown near the northernmost limit for rice paddy cultivation.
AB  - Quantitative trait loci (QTLs) associated with eating quality, grain appearance
      quality and yield-related traits were mapped in recombinant inbred lines (RILs)
      derived from closely related rice (Oryza sativa L. subsp. japonica) cultivars,
      Yukihikari (good eating quality) and Joiku462 (superior eating quality and high
      grain appearance quality). Apparent amylose content (AAC), protein content (PC),
      brown grain length (BGL), brown grain width (BGWI), brown grain thickness (BGT),
      brown grain weight per plant (BGW) and nine yield-related traits were evaluated
      in 133 RILs grown in four different environments in Hokkaido, near the
      northernmost limit for rice paddy cultivation. Using 178 molecular markers, a
      total of 72 QTLs were detected, including three for AAC, eight for PC, two for
      BGL, four for BGWI, seven for BGT, and six for BGW, on chromosomes 1, 2, 3, 4, 6,
      7, 8, 9, 11 and 12. Fifteen intervals were found to harbor multiple QTLs
      affecting these different traits, with most of these QTL clusters located on
      chromosomes 4, 6, 8, 9 and 12. These QTL findings should facilitate gene
      isolation and breeding application for improvement of eating quality, grain
      appearance quality and yield of rice cultivars.

PMID- 28744173
TI  - Variability of arginine content and yield components in Valencia peanut
      germplasm.
AB  - Peanut seeds are rich in arginine, an amino acid that has several positive
      effects on human health. Establishing the genetic variability of arginine content
      in peanut will be useful for breeding programs that have high arginine as one of
      their goals. The objective of this study was to evaluate the variation of
      arginine content, pods/plant, seeds/pod, seed weight, and yield in Valencia
      peanut germplasm. One hundred and thirty peanut genotypes were grown under field
      condition for two years. A randomized complete block design with three
      replications was used for this study. Arginine content was analyzed in peanut
      seeds at harvest using spectrophotometry. Yield and yield components were
      recorded for each genotype. Significant differences in arginine content and yield
      components were found in the tested Valencia peanut germplasm. Arginine content
      ranged from 8.68-23.35 MUg/g seed. Kremena was the best overall genotype of high
      arginine content, number of pods/plant, 100 seed weight and pod yield.

PMID- 28744174
TI  - Analysis of cold resistance and identification of SSR markers linked to cold
      resistance genes in Brassica rapa L.
AB  - Currently, cold temperatures are one of the main factors threatening rapeseed
      production worldwide; thus, it is imperative to identify cold-resistant germplasm
      and to cultivate cold-resistant rapeseed varieties. In this study, the cold
      resistance of four Brassica rapa varieties was analyzed. The cold resistance of
      Longyou6 and Longyou7 was better than that of Tianyou2 and Tianyou4. Thus, an F2
      population derived from Longyou6 and Tianyou4 was used to study the correlation
      of cold resistance and physiological indexes. Our results showed that the degree
      of frost damage was related to the relative conductivity and MDA content (r1 =
      0.558 and r2 = 0.447, respectively). In order to identify the markers related to
      cold resistance, 504 pairs of SSR (simple sequence repeats) primers were used to
      screen the two parents and F2 population. Four and five SSR markers had highly
      significant positive correlation to relative conductivity and MDA, respectively.
      In addition, three of these SSR markers had a highly significant positive
      correlation to both of these two indexes. These three SSR markers were
      subsequently confirmed to be used to distinguish between cold-resistant and non
      cold-resistant varieties. The results of this study will lay a solid foundation
      for the mapping of cold-resistant genes and molecular markers assisted selection
      for the cold-resistance.

PMID- 28744175
TI  - Genetic variation of world soybean maturity date and geographic distribution of
      maturity groups.
AB  - The maturity date of soybean (Glycine max (L.) Merr.) is sensitive to
      photoperiod, which varies with latitude and growing seasons. The maturity group
      (MG) system, composed of 13 MGs, is a major approach in characterizing varieties'
      ecological properties and adaptable areas. A total of 512 world soybean
      varieties, including 48 MG checks, were tested at a major site (Nanjing, 32.04
      degrees N) with portions tested in supplementary sites (Heihe, 50.22 degrees N;
      Mudanjiang, 44.60 degrees N; Jining, 35.38 degrees N and Nanning, 22.84 degrees
      N) in China to explore the world-wide MG distribution. The maturity date of the
      world soybean varied greatly (75-201 d) in Nanjing. Along with soybeans
      disseminated to new areas, the MGs further expanded during the last 70 years from
      MG I-VII to the early MG 0-000 in the north continents and to the late MG VIII-X
      in the south continents with the growth period structure differentiated into two
      subgroups in each MG 0-VIII except V. The cluster analysis among MGs and
      subgroups using genome-wide markers validated the MG sequential emergence order
      and the subgroup differentiation in eight MGs. For future evaluation, in addition
      to one major site (Nanjing), one supplementary southern site (Nanning) and one
      supplementary northern site (Heihe) are sufficient.

PMID- 28744176
TI  - Embryo sac chromosome doubling in Populus alba * P. glandulosa induced by high
      temperature exposure to produce triploids.
AB  - To determine the effects of the hours after pollination and the treatment
      durations on triploid production and reveal the effective stages of embryo sac
      chromosome doubling by high temperature exposure. At least three catkins were
      sampled, and 80 ovules were used for the determination of the embryo sac
      developmental process. Catkins (2-74 h after pollination) were treated to induce
      embryo sac chromosome doubling. Cytological observations revealed that the embryo
      sac development was a consecutive and asynchronous process. Fertilization
      occurred 50 h after pollination. In the offspring seedlings, 167 triploids were
      detected and the highest efficiency of triploid production was 87.0%. Among all
      the induced triploids, the most effective treatment period of inducing embryo sac
      chromosome doubling is from 26 to 50 h after pollination, and 121 triploids were
      obtained, representing 72.46% of the sum of all triploids. GLM-Univariate
      analysis indicated significant differences among the hours after pollination (F =
      4.516, p = 0.045). However, the differences between the treatment durations (F =
      0.077, p = 0.791) were not significant. Correlation analysis between the
      proportion of each embryo sac's developmental stage and the percentage of
      triploid production indicated that the third mitotic division may be the most
      effective stage for 2n female gamete induction.

PMID- 28744177
TI  - Analysis of genetic diversity of rapeseed genetic resources in Japan and core
      collection construction.
AB  - Diversity analysis of rapeseed accessions preserved in the Japanese Genebank can
      provide valuable information for breeding programs. In this study, 582 accessions
      were genotyped with 30 SSR markers covering all 19 rapeseed chromosomes. These
      markers amplified 311 alleles (10.37 alleles per marker; range, 3-39). The
      genetic diversity of Japanese accessions was lower than that of overseas
      accessions. Analysis of molecular variance indicated significant genetic
      differentiation between Japanese and overseas accessions. Small but significant
      differences were found among geographical groups in Japan, and genetic
      differentiation tended to increase with geographical distance. STRUCTURE analysis
      indicated the presence of two main genetic clusters in the NARO rapeseed
      collection. With the membership probabilities threshold, 227 accessions mostly
      originating from overseas were assigned to one subgroup, and 276 accessions
      mostly originating from Japan were assigned to the other subgroup. The remaining
      79 accessions are assigned to admixed group. The core collection constructed
      comprises 96 accessions of diverse origin. It represents the whole collection
      well and thus it may be useful for rapeseed genetic research and breeding
      programs. The core collection improves the efficiency of management, evaluation,
      and utilization of genetic resources.

PMID- 28744178
TI  - Wheat multiple synthetic derivatives: a new source for heat stress tolerance
      adaptive traits.
AB  - Heat stress is detrimental to wheat (Triticum aestivum L.) productivity. In this
      study, we aimed to select heat-tolerant plants from a multiple synthetic
      derivatives (MSD) population and evaluate their agronomic and physiological
      traits. We selected six tolerant plants from the population with the background
      of the cultivar 'Norin 61' (N61) and established six MNH (MSD population of N61
      selected as heat stress-tolerant) lines. We grew these lines with N61 in the
      field and growth chamber. In the field, we used optimum and late sowings to
      ensure plant exposure to heat. In the growth chamber, in addition to N61, we used
      the heat-tolerant cultivars 'Gelenson' and 'Bacanora'. We confirmed that MNH2 and
      MNH5 lines acquired heat tolerance. These lines had higher photosynthesis and
      stomata conductance and exhibited no reduction in grain yield and biomass under
      heat stress compared to N61. We noticed that N61 had relatively good adaptability
      to heat stress. Our results indicate that the MSD population includes the
      diversity of Aegilops tauschii and is a promising resource to uncover useful
      quantitative traits derived from this wild species. Selected lines could be
      useful for heat stress tolerance breeding.

PMID- 28744179
TI  - Determination of drought tolerance related traits in Helianthus argophyllus,
      Helianthus annuus, and their hybrids.
AB  - Drought is a major constraint for sunflower (Helianthus annuus) production
      worldwide. Drought tolerance traits have been identified in the related wild
      species Helianthus argophyllus. This study was initiated to develop sunflower
      drought-tolerant genotypes by crossing cultivated sunflower with this species and
      analyze drought tolerance traits in the H. annuus and H. argophyllus populations,
      H. annuus intraspecific hybrids, and H. annuus * H. argophyllus interspecific
      hybrids along with the commercial hybrid Hysun-33 under three stress regimes:
      exogenous application of ABA, both by foliar spray and irrigation, and 5% PEG
      induced osmotic stress. H. argophyllus populations had a significantly lower leaf
      area and higher water-use efficiency and leaf cuticular wax content under all
      treatments, and maintained a higher net photosynthetic rate and stomatal
      conductance under osmotic stress. Small leaf area and high cuticular waxes
      content of the wild species were, however, not inherited in interspecific hybrids
      which suggested for selection in F2 for these traits. Therefore, transgressive
      plants were selected in the F2 population to establish F3 plant progenies with
      silver-leafed canopy of H. argophyllus which showed higher achene yield under
      stress condition. These results are discussed with a view to using H. argophyllus
      to improve drought tolerance in cultivated sunflower.

PMID- 28744180
TI  - Mutant selection in the self-incompatible plant radish (Raphanus sativus L. var.
      sativus) using two-step TILLING.
AB  - Radish (Raphanus sativus L. var. sativus), a widely cultivated root vegetable
      crop, possesses a large sink organ (the root), implying that photosynthetic
      activity in radish can be enhanced by altering both the source and sink capacity
      of the plant. However, since radish is a self-incompatible plant, improved
      mutation-breeding strategies are needed for this crop. TILLING (Targeting Induced
      Local Lesions IN Genomes) is a powerful method used for reverse genetics. In this
      study, we developed a new TILLING strategy involving a two-step mutant selection
      process for mutagenized radish plants: the first selection is performed to
      identify a BC1M1 line, that is, progenies of M1 plants crossed with wild-type,
      and the second step is performed to identify BC1M1 individuals with mutations. We
      focused on Rubisco as a target, since Rubisco is the most abundant plant protein
      and a key photosynthetic enzyme. We found that the radish genome contains six
      RBCS genes and one pseudogene encoding small Rubisco subunits. We screened 955
      EMS-induced BC1M1 lines using our newly developed TILLING strategy and obtained
      six mutant lines for the six RsRBCS genes, encoding proteins with four different
      types of amino acid substitutions. Finally, we selected a homozygous mutant and
      subjected it to physiological measurements.

PMID- 28744181
TI  - Identification of quantitative trait loci for flowering time by a combination of
      restriction site-associated DNA sequencing and bulked segregant analysis in
      soybean.
AB  - Soybean (Glycine max) has a paleopolyploid genome, and many re-sequencing
      experiments to characterize soybean genotypes have been conducted using next
      generation sequencing platforms. The accumulation of information about single
      nucleotide polymorphisms (SNPs) throughout the soybean genome has accelerated
      identification of genomic regions related to agronomically important traits
      through association studies. However, although many efficient mapping techniques
      that use next-generation sequencing are available, the number of practical
      approaches to identify genes/loci is still limited. In this study, we used a
      combination of restriction site-associated DNA sequencing (RAD-seq) and bulk
      segregant analysis (BSA) to identify quantitative trait locus (QTLs) for
      flowering time in a segregating population derived from a cross between Japanese
      soybean cultivars. Despite the homogeneous genetic background of the parents,
      over 7000 SNPs were identified and can be used to detect QTLs by RAD-seq BSA
      analysis. By comparing genotype frequency between early and late-flowering bulks
      from the F3 segregating population, we identified a QTL on Gm10, which
      corresponds to the previously identified E2 locus, and a QTL on Gm04, which is
      close to the E8 locus. Out of these SNPs, more than 2000 were easily converted to
      conventional DNA markers. Our approach would improve the efficiency of genetic
      mapping.

PMID- 28744182
TI  - Fine mapping of qSKC-1, a major quantitative trait locus for shoot K+
      concentration, in rice seedlings grown under salt stress.
AB  - Shoot K+ concentration (SKC) is an important physiological parameter used to
      evaluate salt tolerance at the seedling stage in rice (Oryza sativa L.). qSKC-1,
      a major quantitative trait locus for SKC in rice under salt stress, was detected
      on chromosome 1 using three F2 populations constructed by crossing 'Nipponbare'
      and its two salt-sensitive mutants (rss2 and rss4) with an indica cultivar
      'Zhaiyeqing8' ('ZYQ8'). In this study, the chromosomal location of qSKC-1 was
      determined precisely by fine mapping. First, the presence of qSKC-1 was confirmed
      by QTL analysis of a re-constructed 'Nipponbare' * 'ZYQ8' F2 population. Then, F2
      plants in which recombination events had occurred near qSKC-1 were identified
      from the 'Nipponbare' * 'ZYQ8' and rss4 * 'ZYQ8' F2 populations, and their
      phenotypic values were confirmed by progeny tests. Eventually, by analyzing
      recombination events in these recombinants, the qSKC-1 locus was mapped precisely
      to 445 kb between markers RM578 and IM8854. These results will facilitate map
      based cloning of the qSKC-1 locus.

PMID- 28744183
TI  - High-density ddRAD linkage and yield-related QTL mapping delimits a chromosomal
      region responsible for oil content in rapeseed (Brassica napus L.).
AB  - Rapeseed (Brassica napus L.) is one of the most important oil crops almost all
      over the world. Seed-related traits, including oil content (OC), silique length
      (SL), seeds per silique (SS), and seed weight (SW), are primary targets for oil
      yield improvement. To dissect the genetic basis of these traits, 192 recombinant
      inbred lines (RILs) were derived from two parents with distinct oil content and
      silique length. High-density linkage map with a total length of 1610.4 cM were
      constructed using 1,329 double-digestion restriction site associated DNA (ddRAD)
      markers, 107 insertion/deletions (INDELs), and 90 well-distributed simple
      sequence repeats (SSRs) markers. A total of 37 consensus quantitative trait loci
      (QTLs) were detected for the four traits, with individual QTL explained 3.1-12.8%
      of the phenotypic variations. Interestingly, one OC consensus QTL (cqOCA10b) on
      chromosome A10 was consistently detected in all three environments, and explained
      9.8% to 12.8% of the OC variation. The locus was further delimited into an
      approximately 614 kb genomic region, in which the flanking markers could be
      further evaluated for marker-assisted selection in rapeseed OC improvement and
      the candidate genes targeted for map-based cloning and genetic manipulation.

PMID- 28744184
TI  - Genetic analysis for rice seedling vigor and fine mapping of a major QTL qSSL1b
      for seedling shoot length.
AB  - Seedling vigor is an important agricultural trait as direct-seeded rice
      technology becomes widely applied. In order to investigate the genetic mechanisms
      underlying seedling vigor in rice, seeds of 132 recombinant inbred lines (RILs)
      derived from 93-11 and PA64s, harvested from Lingshui and Hangzhou were
      cultivated in the nutrient solution, and four indices for seedling vigor were
      measured including seedling shoot length (SSL), seedling root length (SRL),
      seedling wet weight (SWW) and seedling dry weight (SDW). Significant correlations
      were observed among the indices, and also between 1000-seed weight (TSW) and SWW
      or SDW. Combined with a high-resolution genetic map generated from sequencing of
      the RILs, 65 quantitative trait loci (QTLs) were detected on all chromosomes with
      interval of 1.93 Mb on average. Among 57 QTLs for seedling vigor, 28 were
      detected from seeds harvested in both sites and 33 were first identified. With
      BC3F2 derived from 93-11 and a CSSL harboring segments from PA64s in 93-11
      background, a major QTL for SSL, qSSL1b was fine mapped within 80.5 kb between
      two InDel markers. Our study provides a platform for further cloning of the QTL
      and dissecting the molecular basis for seedling vigor at early seedling stage in
      rice.

PMID- 28744185
TI  - Direct quantitative evaluation of disease symptoms on living plant leaves growing
      under natural light.
AB  - Leaf color is an important indicator when evaluating plant growth and responses
      to biotic/abiotic stress. Acquisition of images by digital cameras allows
      analysis and long-term storage of the acquired images. However, under field
      conditions, where light intensity can fluctuate and other factors (shade,
      reflection, and background, etc.) vary, stable and reproducible measurement and
      quantification of leaf color are hard to achieve. Digital scanners provide fixed
      conditions for obtaining image data, allowing stable and reliable comparison
      among samples, but require detached plant materials to capture images, and the
      destructive processes involved often induce deformation of plant materials
      (curled leaves and faded colors, etc.). In this study, by using a lightweight
      digital scanner connected to a mobile computer, we obtained digital image data
      from intact plant leaves grown in natural-light greenhouses without detaching the
      targets. We took images of soybean leaves infected by Xanthomonas campestris pv.
      glycines, and distinctively quantified two disease symptoms (brown lesions and
      yellow halos) using freely available image processing software. The image data
      were amenable to quantitative and statistical analyses, allowing precise and
      objective evaluation of disease resistance.

PMID- 28744186
TI  - Breeding of a new potato variety 'Nagasaki Kogane' with high eating quality, high
      carotenoid content, and resistance to diseases and pests.
AB  - 'Nagasaki Kogane' is a new potato variety bred from a cross between 'Saikai 35'
      as a female parent and 'Saikai 33' as a male. 'Saikai 35' is resistant to
      bacterial wilt, contains the H1 and Rychc genes for resistance to the potato cyst
      nematode (PCN) and potato virus Y (PVY), respectively, and has high carotenoid
      content, while 'Saikai 33' has large and high-yielding tubers and is resistant to
      both bacterial wilt and PCN. The carotenoid content of 'Nagasaki Kogane' is
      higher than that of 'Dejima', a common double cropping variety. The taste quality
      of steamed 'Nagasaki Kogane' is comparable to that of 'Inca-no-mezame' tubers,
      which has high levels of carotenoid, and superior to 'Nishiyutaka', another
      popular double cropping variety. 'Nagasaki Kogane' is suitable for French fries,
      because its tuber has high starch content. The marketable yield of 'Nagasaki
      Kogane' was higher than that of 'Inca-no-mezame' in spring cropping, although it
      was lower than that of 'Nishiyutaka' in double cropping regions. 'Nagasaki
      Kogane' tubers are larger on average than 'Inca-no-mezame' tubers in spring
      cropping. Moreover, the 'Nagasaki Kogane' variety is resistant to PCN and PVY,
      and exhibits a high level of resistance to bacterial wilt.

PMID- 28744187
TI  - Spatiotemporal Relationship of Brain Pathways during Human Fetal Development
      Using High-Angular Resolution Diffusion MR Imaging and Histology.
AB  - In this study, we aimed to identify major fiber pathways and their spatiotemporal
      relationships within transient fetal zones in the human fetal brain by comparing
      postmortem high-angular resolution diffusion MR imaging (HARDI) in combination
      with deterministic streamline tractography and histology. Diffusion weighted
      imaging was performed on postmortem human fetal brains [N = 9, age = 18-34 post
      conceptual weeks (PCW)] that were grossly normal with no pathologic
      abnormalities. After HARDI was performed, the fibers were reconstructed using Q
      ball algorithm and deterministic streamline tractography. The position of major
      fiber pathways within transient fetal zones was identified both on diffusion
      weighted images and on histological sections. Our major findings include: (1) the
      development of massive projection fibers by 18 PCW, as compared to most
      association fibers (with the exception of limbic fibers) which have only begun to
      emerge, (2) the characteristic laminar distribution and sagittal plane geometry
      of reconstructed fibers throughout development, (3) the protracted prenatal
      development shown of the corpus collosum and its' associated fibers, as well as
      the association fibers, and (4) the predomination of radial coherence in the
      telencephalon (i.e., majority of streamlines in the telencephalic wall were
      radially oriented) during early prenatal period (24 PCW). In conclusion,
      correlation between histology and HARDI (in combination with Q-ball
      reconstruction and deterministic streamline tractography) allowed us to detect
      sequential development of fiber systems (projection, callosal, and association),
      their spatial relations with transient fetal zones, and their geometric
      properties.

PMID- 28744188
TI  - Circadian Metabolomics in Time and Space.
AB  - Circadian rhythms are widely known to govern human health and disease, but
      specific pathogenic mechanisms linking circadian disruption to metabolic diseases
      are just beginning to come to light. This is thanks in part to the development
      and application of various "omics"-based tools in biology and medicine. Current
      high-throughput technologies allow for the simultaneous monitoring of multiple
      dynamic cellular events over time, ranging from gene expression to metabolite
      abundance and sub-cellular localization. These fundamental temporal and spatial
      perspectives have allowed for a more comprehensive understanding of how various
      dynamic cellular events and biochemical processes are related in health and
      disease. With advances in technology, metabolomics has become a more routine
      "omics" approach for studying metabolism, and "circadian metabolomics" (i.e.,
      studying the 24-h metabolome) has recently been undertaken by several groups. To
      date, circadian metabolomes have been reported for human serum, saliva, breath,
      and urine, as well as tissues from several species under specific disease or
      mutagenesis conditions. Importantly, these studies have consistently revealed
      that 24-h rhythms are prevalent in almost every tissue and metabolic pathway.
      Furthermore, these circadian rhythms in tissue metabolism are ultimately linked
      to and directed by internal 24-h biological clocks. In this review, we will
      attempt to put these data-rich circadian metabolomics experiments into
      perspective to find out what they can tell us about metabolic health and disease,
      and what additional biomarker potential they may reveal.

PMID- 28744189
TI  - Self-Recalibrating Surface EMG Pattern Recognition for Neuroprosthesis Control
      Based on Convolutional Neural Network.
AB  - Hand movement classification based on surface electromyography (sEMG) pattern
      recognition is a promising approach for upper limb neuroprosthetic control.
      However, maintaining day-to-day performance is challenged by the non-stationary
      nature of sEMG in real-life operation. In this study, we propose a self
      recalibrating classifier that can be automatically updated to maintain a stable
      performance over time without the need for user retraining. Our classifier is
      based on convolutional neural network (CNN) using short latency dimension-reduced
      sEMG spectrograms as inputs. The pretrained classifier is recalibrated routinely
      using a corrected version of the prediction results from recent testing sessions.
      Our proposed system was evaluated with the NinaPro database comprising of hand
      movement data of 40 intact and 11 amputee subjects. Our system was able to
      achieve ~10.18% (intact, 50 movement types) and ~2.99% (amputee, 10 movement
      types) increase in classification accuracy averaged over five testing sessions
      with respect to the unrecalibrated classifier. When compared with a support
      vector machine (SVM) classifier, our CNN-based system consistently showed higher
      absolute performance and larger improvement as well as more efficient training.
      These results suggest that the proposed system can be a useful tool to facilitate
      long-term adoption of prosthetics for amputees in real-life applications.

PMID- 28744191
TI  - Event-Related Potentials in a Cued Go-NoGo Task Associated with Executive
      Functions in Adolescents with Autism Spectrum Disorder; A Case-Control Study.
AB  - Executive functions are often affected in autism spectrum disorders (ASD). The
      underlying biology is however not well known. In the DSM-5, ASD is characterized
      by difficulties in two domains: Social Interaction and Repetitive and Restricted
      Behavior, RRB. Insistence of Sameness is part of RRB and has been reported
      related to executive functions. We aimed to identify differences between ASD and
      typically developing (TD) adolescents in Event Related Potentials (ERPs)
      associated with response preparation, conflict monitoring and response inhibition
      using a cued Go-NoGo paradigm. We also studied the effect of age and emotional
      content of paradigm related to these ERPs. We investigated 49 individuals with
      ASD and 49 TD aged 12-21 years, split into two groups below (young) and above
      (old) 16 years of age. ASD characteristics were quantified by the Social
      Communication Questionnaire (SCQ) and executive functions were assessed with the
      Behavior Rating Inventory of Executive Function (BRIEF), both parent-rated.
      Behavioral performance and ERPs were recorded during a cued visual Go-NoGo task
      which included neutral pictures (VCPT) and pictures of emotional faces (ECPT).
      The amplitudes of ERPs associated with response preparation, conflict monitoring,
      and response inhibition were analyzed. The ASD group showed markedly higher
      scores than TD in both SCQ and BRIEF. Behavioral data showed no case-control
      differences in either the VCPT or ECPT in the whole group. While there were no
      significant case-control differences in ERPs from the combined VCPT and ECPT in
      the whole sample, the Contingent Negative Variation (CNV) was significantly
      enhanced in the old ASD group (p = 0.017). When excluding ASD with comorbid ADHD
      we found a significantly increased N2 NoGo (p = 0.016) and N2-effect (p = 0.023)
      for the whole group. We found no case-control differences in the P3-components.
      Our findings suggest increased response preparation in adolescents with ASD older
      than 16 years and enhanced conflict monitoring in ASD without comorbid ADHD
      during a Go-NoGo task. The current findings may be related to Insistence of
      Sameness in ASD. The pathophysiological underpinnings of executive dysfunction
      should be further investigated to learn more about how this phenomenon is related
      to core characteristics of ASD.

PMID- 28744192
TI  - Macroanatomical Landmarks Featuring Junctions of Major Sulci and Fissures and
      Scalp Landmarks Based on the International 10-10 System for Analyzing Lateral
      Cortical Development of Infants.
AB  - The topographic relationships between the macroanatomical structure of the
      lateral cortex, including sulci and fissures, and anatomical landmarks on the
      external surface of the head are known to be consistent. This allows the
      coregistration of EEG electrodes or functional near-infrared spectroscopy over
      the scalp with underlying cortical regions. However, limited information is
      available as to whether the topographic relationships are maintained in rapidly
      developing infants, whose brains and heads exhibit drastic growth. We used MRIs
      of infants ranging in age from 3 to 22 months old, and identified 20
      macroanatomical landmarks, featuring the junctions of major sulci and fissures,
      as well as cranial landmarks and virtually determined positions of the
      international 10-20 and 10-10 systems. A Procrustes analysis revealed
      developmental trends in changes of shape in both the cortex and head. An analysis
      of Euclidian distances between selected pairs of cortical landmarks at standard
      stereotactic coordinates showed anterior shifts of the relative positions of the
      premotor and parietal cortices with age. Finally, cortical landmark positions and
      their spatial variability were compared with 10-10 landmark positions. The
      results indicate that variability in the distribution of each macroanatomical
      landmark was much smaller than the pitch of the 10-10 landmarks. This study
      demonstrates that the scalp-based 10-10 system serves as a good frame of
      reference in infants not only for assessing the development of the macroanatomy
      of the lateral cortical structure, but also for functional studies of cortical
      development using transcranial modalities such as EEG and fNIRS.

PMID- 28744190
TI  - Hypoxia in CNS Pathologies: Emerging Role of miRNA-Based Neurotherapeutics and
      Yoga Based Alternative Therapies.
AB  - Cellular respiration is a vital process for the existence of life. Any condition
      that results in deprivation of oxygen (also termed as hypoxia) may eventually
      lead to deleterious effects on the functioning of tissues. Brain being the
      highest consumer of oxygen is prone to increased risk of hypoxia-induced
      neurological insults. This in turn has been associated with many diseases of
      central nervous system (CNS) such as stroke, Alzheimer's, encephalopathy etc.
      Although several studies have investigated the pathophysiological mechanisms
      underlying ischemic/hypoxic CNS diseases, the knowledge about protective
      therapeutic strategies to ameliorate the affected neuronal cells is meager. This
      has augmented the need to improve our understanding of the hypoxic and ischemic
      events occurring in the brain and identify novel and alternate treatment
      modalities for such insults. MicroRNA (miRNAs), small non-coding RNA molecules,
      have recently emerged as potential neuroprotective agents as well as targets,
      under hypoxic conditions. These 18-22 nucleotide long RNA molecules are profusely
      present in brain and other organs and function as gene regulators by cleaving and
      silencing the gene expression. In brain, these are known to be involved in
      neuronal differentiation and plasticity. Therefore, targeting miRNA expression
      represents a novel therapeutic approach to intercede against hypoxic and ischemic
      brain injury. In the first part of this review, we will discuss the
      neurophysiological changes caused as a result of hypoxia, followed by the
      contribution of hypoxia in the neurodegenerative diseases. Secondly, we will
      provide recent updates and insights into the roles of miRNA in the regulation of
      genes in oxygen and glucose deprived brain in association with circadian rhythms
      and how these can be targeted as neuroprotective agents for CNS injuries.
      Finally, we will emphasize on alternate breathing or yogic interventions to
      overcome the hypoxia associated anomalies that could ultimately lead to
      improvement in cerebral perfusion.

PMID- 28744193
TI  - On the Origin of the 1,000 Hz Peak in the Spectrum of the Human Tympanic
      Electrical Noise.
AB  - The spectral analysis of the spontaneous activity recorded with an electrode
      positioned near the round window of the guinea pig cochlea shows a broad energy
      peak between 800 and 1,000 Hz. This spontaneous electric activity is called round
      window noise or ensemble background activity. In guinea pigs, the proposed origin
      of this peak is the random sum of the extracellular field potentials generated by
      action potentials of auditory nerve neurons. In this study, we used a non
      invasive method to record the tympanic electric noise (TEN) in humans by means of
      a tympanic wick electrode. We recorded a total of 24 volunteers, under silent
      conditions or in response to stimuli of different modalities, including auditory,
      vestibular, and motor activity. Our results show a reliable peak of spontaneous
      activity at ~1,000 Hz in all studied subjects. In addition, we found stimulus
      driven responses with broad-band noise that in most subjects produced an increase
      in the magnitude of the energy band around 1,000 Hz (between 650 and 1,200 Hz).
      Our results with the vestibular stimulation were not conclusive, as we found
      responses with all caloric stimuli, including 37 degrees C. No responses were
      observed with motor tasks, like eye movements or blinking. We demonstrate the
      feasibility of recording neural activity from the electric noise of the tympanic
      membrane with a non-invasive method. From our results, we suggest that the 1,000
      Hz component of the TEN has a mixed origin including peripheral and central
      auditory pathways. This research opens up the possibility of future clinical non
      invasive techniques for the functional study of auditory and vestibular nerves in
      humans.

PMID- 28744194
TI  - Navigating Monogamy: Nonapeptide Sensitivity in a Memory Neural Circuit May Shape
      Social Behavior and Mating Decisions.
AB  - The role of memory in mating systems is often neglected despite the fact that
      most mating systems are defined in part by how animals use space. Monogamy, for
      example, is usually characterized by affiliative (e.g., pairbonding) and
      defensive (e.g., mate guarding) behaviors, but a high degree of spatial overlap
      in home range use is the easiest defining feature of monogamous animals in the
      wild. The nonapeptides vasopressin and oxytocin have been the focus of much
      attention for their importance in modulating social behavior, however this work
      has largely overshadowed their roles in learning and memory. To date, the
      understanding of memory systems and mechanisms governing social behavior have
      progressed relatively independently. Bridging these two areas will provide a
      deeper appreciation for understanding behavior, and in particular the mechanisms
      that mediate reproductive decision-making. Here, I argue that the ability to mate
      effectively as monogamous individuals is linked to the ability to track
      conspecifics in space. I discuss the connectivity across some well-known social
      and spatial memory nuclei, and propose that the nonapeptide receptors within
      these structures form a putative "socio-spatial memory neural circuit." This
      purported circuit may function to integrate social and spatial information to
      shape mating decisions in a context-dependent fashion. The lateral septum and/or
      the nucleus accumbens, and neuromodulation therein, may act as an intermediary to
      relate socio-spatial information with social behavior. Identifying mechanisms
      responsible for relating information about the social world with mechanisms
      mediating mating tactics is crucial to fully appreciate the suite of factors
      driving reproductive decisions and social decision-making.

PMID- 28744195
TI  - Machine Learning Approach for Classifying Multiple Sclerosis Courses by Combining
      Clinical Data with Lesion Loads and Magnetic Resonance Metabolic Features.
AB  - Purpose: The purpose of this study is classifying multiple sclerosis (MS)
      patients in the four clinical forms as defined by the McDonald criteria using
      machine learning algorithms trained on clinical data combined with lesion loads
      and magnetic resonance metabolic features. Materials and Methods: Eighty-seven MS
      patients [12 Clinically Isolated Syndrome (CIS), 30 Relapse Remitting (RR), 17
      Primary Progressive (PP), and 28 Secondary Progressive (SP)] and 18 healthy
      controls were included in this study. Longitudinal data available for each MS
      patient included clinical (e.g., age, disease duration, Expanded Disability
      Status Scale), conventional magnetic resonance imaging and spectroscopic imaging.
      We extract N-acetyl-aspartate (NAA), Choline (Cho), and Creatine (Cre)
      concentrations, and we compute three features for each spectroscopic grid by
      averaging metabolite ratios (NAA/Cho, NAA/Cre, Cho/Cre) over good quality voxels.
      We built linear mixed-effects models to test for statistically significant
      differences between MS forms. We test nine binary classification tasks on
      clinical data, lesion loads, and metabolic features, using a leave-one-patient
      out cross-validation method based on 100 random patient-based bootstrap
      selections. We compute F1-scores and BAR values after tuning Linear Discriminant
      Analysis (LDA), Support Vector Machines with gaussian kernel (SVM-rbf), and
      Random Forests. Results: Statistically significant differences were found between
      the disease starting points of each MS form using four different response
      variables: Lesion Load, NAA/Cre, NAA/Cho, and Cho/Cre ratios. Training SVM-rbf on
      clinical and lesion loads yields F1-scores of 71-72% for CIS vs. RR and CIS vs.
      RR+SP, respectively. For RR vs. PP we obtained good classification results
      (maximum F1-score of 85%) after training LDA on clinical and metabolic features,
      while for RR vs. SP we obtained slightly higher classification results (maximum
      F1-score of 87%) after training LDA and SVM-rbf on clinical, lesion loads and
      metabolic features. Conclusions: Our results suggest that metabolic features are
      better at differentiating between relapsing-remitting and primary progressive
      forms, while lesion loads are better at differentiating between relapsing
      remitting and secondary progressive forms. Therefore, combining clinical data
      with magnetic resonance lesion loads and metabolic features can improve the
      discrimination between relapsing-remitting and progressive forms.

PMID- 28744196
TI  - Extraocular Motor System Exhibits a Higher Expression of Neurotrophins When
      Compared with Other Brainstem Motor Systems.
AB  - Extraocular motoneurons resist degeneration in diseases such as amyotrophic
      lateral sclerosis. The main objective of the present work was to characterize the
      presence of neurotrophins in extraocular motoneurons and muscles of the adult
      rat. We also compared these results with those obtained from other cranial motor
      systems, such as facial and hypoglossal, which indeed suffer neurodegeneration.
      Immunocytochemical analysis was used to describe the expression of nerve growth
      factor, brain-derived neurotrophic factor and neurotrophin-3 in oculomotor,
      trochlear, abducens, facial, and hypoglossal nuclei of adult rats, and Western
      blots were used to describe the presence of neurotrophins in extraocular, facial
      (buccinator), and tongue muscles, which are innervated by the above-mentioned
      motoneurons. In brainstem samples, brain-derived neurotrophic factor was present
      both in extraocular and facial motoneuron somata, and to a lesser degree, in
      hypoglossal motoneurons. Neurotrophin-3 was present in extraocular motor nuclei,
      while facial and hypoglossal motoneurons were almost devoid of this protein.
      Finally, nerve growth factor was not present in the soma of any group of
      motoneurons, although it was present in dendrites of motoneurons located in the
      neuropil. Neuropil optical density levels were higher in extraocular motoneuron
      nuclei when compared with facial and hypoglossal nuclei. Neurotrophins could be
      originated in target muscles, since Western blot analyses revealed the presence
      of the three molecules in all sampled muscles, to a larger extent in extraocular
      muscles when compared with facial and tongue muscles. We suggest that the
      different neurotrophin availability could be related to the particular resistance
      of extraocular motoneurons to neurodegeneration.

PMID- 28744197
TI  - Neuronal Cholesterol Accumulation Induced by Cyp46a1 Down-Regulation in Mouse
      Hippocampus Disrupts Brain Lipid Homeostasis.
AB  - Impairment in cholesterol metabolism is associated with many neurodegenerative
      disorders including Alzheimer's disease (AD). However, the lipid alterations
      underlying neurodegeneration and the connection between altered cholesterol
      levels and AD remains not fully understood. We recently showed that cholesterol
      accumulation in hippocampal neurons, induced by silencing Cyp46a1 gene
      expression, leads to neurodegeneration with a progressive neuronal loss
      associated with AD-like phenotype in wild-type mice. We used a targeted and non
      targeted lipidomics approach by liquid chromatography coupled to high-resolution
      mass spectrometry to further characterize lipid modifications associated to
      neurodegeneration and cholesterol accumulation induced by CYP46A1 inhibition.
      Hippocampus lipidome of normal mice was profiled 4 weeks after cholesterol
      accumulation due to Cyp46a1 gene expression down-regulation at the onset of
      neurodegeneration. We showed that major membrane lipids, sphingolipids and
      specific enzymes involved in phosphatidylcholine and sphingolipid metabolism,
      were rapidly increased in the hippocampus of AAV-shCYP46A1 injected mice. This
      lipid accumulation was associated with alterations in the lysosomal cargoe,
      accumulation of phagolysosomes and impairment of endosome-lysosome trafficking.
      Altogether, we demonstrated that inhibition of cholesterol 24-hydroxylase, key
      enzyme of cholesterol metabolism leads to a complex dysregulation of lipid
      homeostasis. Our results contribute to dissect the potential role of lipids in
      severe neurodegenerative diseases like AD.

PMID- 28744198
TI  - Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through
      Inhibition of Integrin Signaling and Galectin-3 Phosphorylation.
AB  - Galectin-3, a member of the galectin protein family, has been found to regulate
      cell proliferation, inhibit apoptosis and promote inflammatory responses.
      Galectin-3 is also expressed in the adult rat hippocampus, but its role in
      learning and memory function is not known. Here, we found that contextual fear
      conditioning training, spatial training or injection of NMDA into the rat CA1
      area each dramatically decreased the level of endogenous galectin-3 expression.
      Overexpression of galectin-3 impaired fear memory, whereas galectin-3 knockout
      (KO) enhanced fear retention, spatial memory and hippocampal long-term
      potentiation. Galectin-3 was further found to associate with integrin alpha3, an
      association that was decreased after fear-conditioning training. Transfection of
      the rat CA1 area with small interfering RNA against galectin-3 facilitated fear
      memory and increased phosphorylated focal adhesion kinase (FAK) levels, effects
      that were blocked by co-transfection of the FAK phosphorylation-defective mutant
      Flag-FAKY397F. Notably, levels of serine-phosphorylated galectin-3 were decreased
      by fear conditioning training. In addition, blockade of galectin-3
      phosphorylation at Ser-6 facilitated fear memory, whereas constitutive activation
      of galectin-3 at Ser-6 impaired fear memory. Interestingly galectin-1 plays a
      role in fear-memory formation similar to that of galectin-3. Collectively, our
      data provide the first demonstration that galectin-3 is a novel negative
      regulator of memory formation that exerts its effects through both extracellular
      and intracellular mechanisms.

PMID- 28744199
TI  - Differential Impact of miR-21 on Pain and Associated Affective and Cognitive
      Behavior after Spared Nerve Injury in B7-H1 ko Mouse.
AB  - MicroRNAs (miRNAs) are increasingly recognized as regulators of immune and
      neuronal gene expression and are potential master switches in neuropathic pain
      pathophysiology. miR-21 is a promising candidate that may link the immune and the
      pain system. To investigate the pathophysiological role of miR-21 in neuropathic
      pain, we assessed mice deficient of B7 homolog 1 (B7-H1), a major inhibitor of
      inflammatory responses. In previous studies, an upregulation of miR-21 had been
      shown in mouse lymphocytes. Young (8 weeks), middle-aged (6 months), and old (12
      months) B7-H1 ko mice and wildtype littermates (WT) received a spared nerve
      injury (SNI). We assessed thermal withdrawal latencies and mechanical withdrawal
      thresholds. Further, we performed tests for anxiety-like and cognitive behavior.
      Quantitative real time PCR was used to determine miR-21 relative expression in
      peripheral nerves, and dorsal root ganglia (DRG) at distinct time points after
      SNI. We found mechanical hyposensitivity with increasing age of naive B7-H1 ko
      mice. Young and middle-aged B7-H1 ko mice were more sensitive to mechanical
      stimuli compared to WT mice (young: p < 0.01, middle-aged: p < 0.05). Both
      genotypes developed mechanical and heat hypersensitivity (p < 0.05) after SNI,
      without intergroup differences. No relevant differences were found after SNI in
      three tests for anxiety like behavior in B7-H1 ko and WT mice. Also, SNI had no
      effect on cognition. B7-H1 ko and WT mice showed a higher miR-21 expression (p <
      0.05) and invasion of macrophages and T cells in the injured nerve 7 days after
      SNI without intergroup differences. Our study reveals that increased miR-21
      expression in peripheral nerves after SNI is associated with reduced mechanical
      and heat withdrawal thresholds. These results point to a role of miR-21 in the
      pathophysiology of neuropathic pain, while affective behavior and cognition seem
      to be spared. Contrary to expectations, B7-H1 ko mice did not show higher miR-21
      expression than WT mice, thus, a B7-H1 knockout may be of limited relevance for
      the study of miR-21 related pain.

PMID- 28744201
TI  - Calcium Dynamics in Basal Dendrites of Layer 5A and 5B Pyramidal Neurons Is Tuned
      to the Cell-Type Specific Physiological Action Potential Discharge.
AB  - Layer 5 (L5) is a major neocortical output layer containing L5A slender-tufted
      (L5A-st) and L5B thick-tufted (L5B-tt) pyramidal neurons. These neuron types
      differ in their in vivo firing patterns, connectivity and dendritic morphology
      amongst other features, reflecting their specific functional role within the
      neocortical circuits. Here, we asked whether the active properties of the basal
      dendrites that receive the great majority of synaptic inputs within L5 differ
      between these two pyramidal neuron classes. To quantify their active properties,
      we measured the efficacy with which action potential (AP) firing patterns
      backpropagate along the basal dendrites by measuring the accompanying calcium
      transients using two-photon laser scanning microscopy in rat somatosensory cortex
      slices. For these measurements we used both "artificial" three-AP patterns and
      more complex physiological AP patterns that were previously recorded in
      anesthetized rats in L5A-st and L5B-tt neurons in response to whisker
      stimulation. We show that AP patterns with relatively few APs (3APs) evoke a
      calcium response in L5B-tt, but not L5A-st, that is dependent on the temporal
      pattern of the three APs. With more complex in vivo recorded AP patterns, the
      average calcium response was similar in the proximal dendrites but with a decay
      along dendrites (measured up to 100 MUm) of L5B-tt but not L5A-st neurons.
      Interestingly however, the whisker evoked AP patterns-although very different for
      the two cell types-evoke similar calcium responses. In conclusion, although the
      effectiveness with which different AP patterns evoke calcium transients vary
      between L5A-st and L5B-tt cell, the calcium influx appears to be tuned such that
      whisker-evoked calcium transients are within the same dynamic range for both cell
      types.

PMID- 28744200
TI  - Effect of Neuroinflammation on Synaptic Organization and Function in the
      Developing Brain: Implications for Neurodevelopmental and Neurodegenerative
      Disorders.
AB  - The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic
      cues play important roles in shaping and wiring neural connections. The perinatal
      period constitutes a critical time in central nervous system development with
      extensive refinement of neural connections, which are highly sensitive to fetal
      and neonatal compromise, such as inflammatory challenges. Emerging evidence
      suggests that inflammatory cells in the brain such as microglia and astrocytes
      are pivotal in regulating synaptic structure and function. In this article, we
      will review the role of glia cells in synaptic physiology and pathophysiology,
      including microglia-mediated elimination of synapses. We propose that activation
      of the immune system dynamically affects synaptic organization and function in
      the developing brain. We will discuss the role of neuroinflammation in altered
      synaptic plasticity following perinatal inflammatory challenges and potential
      implications for neurodevelopmental and neurodegenerative disorders.

PMID- 28744202
TI  - RNA Misprocessing in C9orf72-Linked Neurodegeneration.
AB  - A large GGGGCC hexanucleotide repeat expansion in the first intron or promoter
      region of the C9orf72 gene is the most common genetic cause of familial and
      sporadic Amyotrophic lateral sclerosis (ALS), a devastating degenerative disease
      of motor neurons, and of Frontotemporal Dementia (FTD), the second most common
      form of presenile dementia after Alzheimer's disease. C9orf72-associated ALS/FTD
      is a multifaceted disease both in terms of its clinical presentation and the
      misregulated cellular pathways contributing to disease progression. Among the
      numerous pathways misregulated in C9orf72-associated ALS/FTD, altered RNA
      processing has consistently appeared at the forefront of C9orf72 research. This
      includes bidirectional transcription of the repeat sequence, accumulation of
      repeat RNA into nuclear foci sequestering specific RNA-binding proteins (RBPs)
      and translation of RNA repeats into dipeptide repeat proteins (DPRs) by repeat
      associated non-AUG (RAN)-initiated translation. Over the past few years the true
      extent of RNA misprocessing in C9orf72-associated ALS/FTD has begun to emerge and
      disruptions have been identified in almost all aspects of the life of an RNA
      molecule, including release from RNA polymerase II, translation in the cytoplasm
      and degradation. Furthermore, several alterations have been identified in the
      processing of the C9orf72 RNA itself, in terms of its transcription, splicing and
      localization. This review article aims to consolidate our current knowledge on
      the consequence of the C9orf72 repeat expansion on RNA processing and draws
      attention to the mechanisms by which several aspects of C9orf72 molecular
      pathology converge to perturb every stage of RNA metabolism.

PMID- 28744203
TI  - Synaptic Ribbon Active Zones in Cone Photoreceptors Operate Independently from
      One Another.
AB  - Cone photoreceptors depolarize in darkness to release glutamate-laden synaptic
      vesicles. Essential to release is the synaptic ribbon, a structure that helps
      organize active zones by clustering vesicles near proteins that mediate
      exocytosis, including voltage-gated Ca2+ channels. Cone terminals have many
      ribbon-style active zones at which second-order neurons receive input. We asked
      whether there are functionally significant differences in local Ca2+ influx among
      ribbons in individual cones. We combined confocal Ca2+ imaging to measure Ca2+
      influx at individual ribbons and patch clamp recordings to record whole-cell ICa
      in salamander cones. We found that the voltage for half-maximal activation (V50)
      of whole cell ICa in cones averaged -38.1 mV +/- 3.05 mV (standard deviation
      [SD]), close to the cone membrane potential in darkness of ca. -40 mV. Ca2+
      signals at individual ribbons varied in amplitude from one another and showed
      greater variability in V50 values than whole-cell ICa, suggesting that Ca2+
      signals can differ significantly among ribbons within cones. After accounting for
      potential sources of technical variability in measurements of Ca2+ signals and
      for contributions from cone-to-cone differences in ICa, we found that the
      variability in V50 values for ribbon Ca2+ signals within individual cones showed
      a SD of 2.5 mV. Simulating local differences in Ca2+ channel activity at two
      ribbons by shifting the V50 value of ICa by +/-2.5 mV (1 SD) about the mean
      suggests that when the membrane depolarizes to -40 mV, two ribbons could
      experience differences in Ca2+ influx of >45%. Further evidence that local Ca2+
      changes at ribbons can be regulated independently was obtained in experiments
      showing that activation of inhibitory feedback from horizontal cells (HCs) to
      cones in paired recordings changed both amplitude and V50 of Ca2+ signals at
      individual ribbons. By varying the strength of synaptic output, differences in
      voltage dependence and amplitude of Ca2+ signals at individual ribbons shape the
      information transmitted from cones to downstream neurons in vision.

PMID- 28744204
TI  - Differences in Social Decision-Making between Proposers and Responders during the
      Ultimatum Game: An EEG Study.
AB  - The Ultimatum Game (UG) is a typical paradigm to investigate social decision
      making. Although the behavior of humans in this task is already well established,
      the underlying brain processes remain poorly understood. Previous investigations
      using event-related potentials (ERPs) revealed three major components related to
      cognitive processes in participants engaged in the responder condition, the early
      ERP component P2, the feedback-related negativity (FRN) and a late positive wave
      (late positive component, LPC). However, the comparison of the ERP waveforms
      between the responder and proposer conditions has never been studied. Therefore,
      to investigate condition-related electrophysiological changes, we applied the UG
      paradigm and compared parameters of the P2, LPC and FRN components in twenty
      healthy participants. For the responder condition, we found a significantly
      decreased amplitude and delayed latency for the P2 component, whereas the mean
      amplitudes of the LPC and FRN increased compared to the proposer condition.
      Additionally, the proposer condition elicited an early component consisting of a
      negative deflection around 190 ms, in the upward slope of the P2, probably as a
      result of early conflict-related processing. Using independent component analysis
      (ICA), we extracted one functional component time-locked to this deflection, and
      with source reconstruction (LAURA) we found the anterior cingulate cortex (ACC)
      as one of the underlying sources. Overall, our findings indicate that intensity
      and time-course of neuronal systems engaged in the decision-making processes
      diverge between both UG conditions, suggesting differential cognitive processes.
      Understanding the electrophysiological bases of decision-making and social
      interactions in controls could be useful to further detect which steps are
      impaired in psychiatric patients in their ability to attribute mental states
      (such as beliefs, intents, or desires) to oneself and others. This ability is
      called mentalizing (also known as theory of mind).

PMID- 28744205
TI  - Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient
      Mice.
AB  - Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of
      basic leucine zipper transcription factors. We previously reported that ATF5
      deficient (ATF5-/-) mice demonstrated abnormal olfactory bulb development due to
      impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than
      ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the
      regulation of proliferation and development of neurons, the physiological role of
      ATF5 in the higher brain remains unknown. Our objective was to investigate the
      physiological role of ATF5 in the higher brain. We performed a comprehensive
      behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice
      exhibited abnormal locomotor activity in the open field test. They also exhibited
      abnormal anxiety-like behavior in the light/dark transition test and open field
      test. Furthermore, ATF5-/- mice displayed reduced social interaction in the
      Crawley's social interaction test and increased pain sensitivity in the hot plate
      test compared with wild type. Finally, behavioral flexibility was reduced in the
      T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated
      that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in
      several brain regions. These results indicate that ATF5 deficiency elicits
      abnormal behaviors and the disturbance of monoamine neurotransmitter levels in
      the brain. The behavioral abnormalities of ATF5-/- mice may be due to the
      disturbance of monoamine levels. Taken together, these findings suggest that ATF5
      /- mice may be a unique animal model of some psychiatric disorders.

PMID- 28744206
TI  - Reward Draws the Eye, Uncertainty Holds the Eye: Associative Learning Modulates
      Distractor Interference in Visual Search.
AB  - Stimuli in our sensory environment differ with respect to their physical salience
      but moreover may acquire motivational salience by association with reward. If we
      repeatedly observed that reward is available in the context of a particular cue
      but absent in the context of another cue the former typically attracts more
      attention than the latter. However, we also may encounter cues uncorrelated with
      reward. A cue with 50% reward contingency may induce an average reward expectancy
      but at the same time induces high reward uncertainty. In the current experiment
      we examined how both values, reward expectancy and uncertainty, affected overt
      attention. Two different colors were established as predictive cues for low
      reward and high reward respectively. A third color was followed by high reward on
      50% of the trials and thus induced uncertainty. Colors then were introduced as
      distractors during search for a shape target, and we examined the relative
      potential of the color distractors to capture and hold the first fixation. We
      observed that capture frequency corresponded to reward expectancy while capture
      duration corresponded to uncertainty. The results may suggest that within trial
      reward expectancy is represented at an earlier time window than uncertainty.

PMID- 28744207
TI  - Preference for Averageness in Faces Does Not Generalize to Non-Human Primates.
AB  - Facial attractiveness is a long-standing topic of active study in both
      neuroscience and social science, motivated by its positive social consequences.
      Over the past few decades, it has been established that averageness is a major
      factor influencing judgments of facial attractiveness in humans. Non-human
      primates share similar social behaviors as well as neural mechanisms related to
      face processing with humans. However, it is unknown whether monkeys, like humans,
      also find particular faces attractive and, if so, which kind of facial traits
      they prefer. To address these questions, we investigated the effect of
      averageness on preferences for faces in monkeys. We tested three adult male
      rhesus macaques using a visual paired comparison (VPC) task, in which they viewed
      pairs of faces (both individual faces, or one individual face and one average
      face); viewing time was used as a measure of preference. We did find that monkeys
      looked longer at certain individual faces than others. However, unlike humans,
      monkeys did not prefer the average face over individual faces. In fact, the more
      the individual face differed from the average face, the longer the monkeys looked
      at it, indicating that the average face likely plays a role in face recognition
      rather than in judgments of facial attractiveness: in models of face recognition,
      the average face operates as the norm against which individual faces are compared
      and recognized. Taken together, our study suggests that the preference for
      averageness in faces does not generalize to non-human primates.

PMID- 28744208
TI  - Neurodevelopmental Hypothesis about the Etiology of Autism Spectrum Disorders.
AB  - Previous models or hypotheses of autism spectral disorder (ASD) failed to take
      into full consideration the chronological and causal developmental trajectory,
      leading to the emergence of diverse phenotypes through a complex interaction
      between individual etiologies and environmental factors. Those phenotypes include
      persistent deficits in social communication and social interaction (criteria A in
      DSM-5), and restricted, repetitive patterns of behavior, interests, or activities
      (criteria B in DSM-5). In this article, we proposed a domain-general model that
      can explain criteria in DSM-5 based on the assumption that the same etiological
      mechanism would trigger the various phenotypes observed in different individuals
      with ASD. In the model, we assumed the following joint causes as the etiology of
      autism: (1) Hypoplasia of the pons in the brainstem, occurring immediately
      following neural tube closure; and (2) Deficiency in the GABA (gamma-aminobutyric
      acid) developmental switch during the perinatal period. Microstructural
      abnormalities of the pons directly affect both the structural and functional
      development of the brain areas strongly connected to it, especially amygdala. The
      impairment of GABA switch could not only lead to the deterioration of inhibitory
      processing in the neural network, but could also cause abnormal cytoarchitecture.
      We introduced a perspective that atypical development in both brain structure and
      function can give full explanation of diverse phenotypes and pathogenetic
      mechanism of ASD. Finally, we discussed about neural mechanisms underlying the
      phenotypic characteristics of ASD that are not described in DSM-5 but should be
      considered as important foundation: sleep, global precedence, categorical
      perception, intelligence, interoception and motor control.

PMID- 28744209
TI  - Performance Monitoring Applied to System Supervision.
AB  - Nowadays, automation is present in every aspect of our daily life and has some
      benefits. Nonetheless, empirical data suggest that traditional automation has
      many negative performance and safety consequences as it changed task performers
      into task supervisors. In this context, we propose to use recent insights into
      the anatomical and neurophysiological substrates of action monitoring in humans,
      to help further characterize performance monitoring during system supervision.
      Error monitoring is critical for humans to learn from the consequences of their
      actions. A wide variety of studies have shown that the error monitoring system is
      involved not only in our own errors, but also in the errors of others. We
      hypothesize that the neurobiological correlates of the self-performance
      monitoring activity can be applied to system supervision. At a larger scale, a
      better understanding of system supervision may allow its negative effects to be
      anticipated or even countered. This review is divided into three main parts.
      First, we assess the neurophysiological correlates of self-performance monitoring
      and their characteristics during error execution. Then, we extend these results
      to include performance monitoring and error observation of others or of systems.
      Finally, we provide further directions in the study of system supervision and
      assess the limits preventing us from studying a well-known phenomenon: the Out-Of
      the-Loop (OOL) performance problem.

PMID- 28744210
TI  - Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe
      Epilepsy.
AB  - In temporal lobe epilepsy (TLE), the variation of chemical receptor expression
      underlies the basis of neural network activity shifts, resulting in neuronal
      hyperexcitability and epileptiform discharges. However, dynamical mechanisms
      involved in the transitions of TLE are not fully understood, because of the
      neuronal diversity and the indeterminacy of network connection. Hence, based on
      Hodgkin-Huxley (HH) type neurons and Pinsky-Rinzel (PR) type neurons coupling
      with glutamatergic and GABAergic synaptic connections respectively, we propose a
      computational framework which contains dentate gyrus (DG) region and CA3 region.
      By regulating the concentration range of N-methyl-D-aspartate-type glutamate
      receptor (NMDAR), we demonstrate the pyramidal neuron can generate transitions
      from interictal to seizure discharges. This suggests that enhanced endogenous
      activity of NMDAR contributes to excitability in pyramidal neuron. Moreover, we
      conclude that excitatory discharges in CA3 region vary considerably on account of
      the excitatory currents produced by the excitatory pyramidal neuron.
      Interestingly, by changing the backprojection connection, we find that
      glutamatergic type backprojection can promote the dominant frequency of firings
      and further motivate excitatory counterpropagation from CA3 region to DG region.
      However, GABAergic type backprojection can reduce firing rate and block morbid
      counterpropagation, which may be factored into the terminations of TLE. In
      addition, neuronal diversity dominated network shows weak correlation with
      different backprojections. Our modeling and simulation studies provide new
      insights into the mechanisms of seizures generation and connectionism in local
      hippocampus, along with the synaptic mechanisms of this disease.

PMID- 28744211
TI  - Characterization of Spatial Frequency Channels Underlying Disparity Sensitivity
      by Factor Analysis of Population Data.
AB  - It has been suggested that at least two mechanisms mediate disparity processing,
      one for coarse and one for fine disparities. Here we analyze individual
      differences in our previously measured normative dataset on the disparity
      sensitivity as a function of spatial frequency of 61 observers to assess the
      tuning of the spatial frequency channels underlying disparity sensitivity for
      oblique corrugations (Reynaud et al., 2015). Inter-correlations and factor
      analysis of the population data revealed two spatial frequency channels for
      disparity sensitivity: one tuned to high spatial frequencies and one tuned to low
      spatial frequencies. Our results confirm that disparity is encoded by spatial
      frequency channels of different sensitivities tuned to different ranges of
      corrugation frequencies.

PMID- 28744212
TI  - Personalized Offline and Pseudo-Online BCI Models to Detect Pedaling Intent.
AB  - The aim of this work was to design a personalized BCI model to detect pedaling
      intention through EEG signals. The approach sought to select the best among many
      possible BCI models for each subject. The choice was between different processing
      windows, feature extraction algorithms and electrode configurations. Moreover,
      data was analyzed offline and pseudo-online (in a way suitable for real-time
      applications), with a preference for the latter case. A process for selecting the
      best BCI model was described in detail. Results for the pseudo-online processing
      with the best BCI model of each subject were on average 76.7% of true positive
      rate, 4.94 false positives per minute and 55.1% of accuracy. The personalized BCI
      model approach was also found to be significantly advantageous when compared to
      the typical approach of using a fixed feature extraction algorithm and electrode
      configuration. The resulting approach could be used to more robustly interface
      with lower limb exoskeletons in the context of the rehabilitation of stroke
      patients.

PMID- 28744213
TI  - Risk Factors for Post-stroke Depression: A Meta-analysis.
AB  - Background: Stroke not only impacts patients physically but also economically.
      Post-stroke depression (PSD), as a common complication of stroke, always
      obstructs the process of stroke rehabilitation. Accordingly, defining the risk
      factors associated with PSD has extraordinary importance. Although there have
      been many studies investigating the risk factors for PSD, the results are
      inconsistent. Objectives: The objectives of this study were to identify the risk
      factors for PSD by evidence-based medicine. Data sources: A systematic and
      comprehensive database search was performed of PubMed, Medline, CENTRAL,
      EMBASE.com, the Cochrane library and Web of Science for Literature, covering
      publications from January 1, 1998 to November 19, 2016. Study Selection: Studies
      on risk factors for PSD were identified, according to inclusion and exclusion
      criteria. The risk of bias tool, described in the Cochrane Handbook version
      5.1.0, was used to assess the quality of each study. Meta-analysis was performed
      using RevMan 5.3 software. Results: Thirty-six studies were included for review.
      A history of mental illness was the highest ranking modifiable risk factor; other
      risk factors for PSD were female gender, age (<70 years), neuroticism, family
      history, severity of stroke, and level of handicap. Social support was a
      protective factor for PSD. Conclusion: There are many factors that have effects
      on PSD. The severity of stroke is an important factor in the occurrence of PSD.
      Mental history is a possible predictor of PSD. Prevention of PSD requires social
      and family participation.

PMID- 28744214
TI  - Impairments of Speech Comprehension in Patients with Tinnitus-A Review.
AB  - Tinnitus describes the subjective perception of a sound despite the absence of
      external stimulation. Being a sensory symptom the majority of studies focusses on
      the auditory pathway. In the recent years, a series of studies suggested a
      crucial involvement of the limbic system in the manifestation and development of
      chronic tinnitus. Regarding cognitive symptoms, several reviews addressed the
      presence of cognitive impairments in tinnitus as well and concluded that
      attention and memory processes are affected. Despite the importance for social
      communication and the reliance on a highly functional auditory system, speech
      comprehension remains a largely neglected field in tinnitus research. This is why
      we review here the existing literature on speech and language functions in
      tinnitus patients. Reviewed studies suggest that speech comprehension is impaired
      in patients with tinnitus, especially in the presence of competing noise. This is
      even the case in tinnitus patients with normal hearing thresholds. Additionally,
      speech comprehension measures seem independent of other measures such as tinnitus
      severity and perceived tinnitus loudness. According to the majority of authors,
      the speech comprehension difficulties arise as a result of central processes or
      dysfunctional neuroplasticity.

PMID- 28744215
TI  - Safety and Effectiveness of Bivalirudin in Patients Undergoing Percutaneous
      Coronary Intervention: A Systematic Review and Meta-Analysis.
AB  - Recent clinical trials have shown that while bivalirudin exhibits similar
      efficacy with heparin, it offers several advantages over heparin, such as a
      better safety profile. We aimed to evaluate the efficacy and safety of
      bivalirudin use during Percutaneous Coronary Intervention (PCI) in the treatment
      of angina and acute coronary syndrome (ACS). We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, EMBASE,
      and Science Direct from January 1980 to January 2016. Randomized controlled
      trials (RCTs) comparing bivalirudin to heparin during the course of PCI in
      patients with angina or ACS were included. Outcome measures included all-cause
      mortality, myocardial infarction, revascularisation, stent thrombosis, stroke,
      and major bleeding. The selection, quality assessment, and data extraction of the
      included trials were done independently by four authors, and disagreements were
      resolved by consensus. Pooled relative risk (RR) estimates and 95% confidence
      intervals (CIs) were calculated. A total of 12 RCTs involving 44,088 subjects
      were included. Bivalirudin appeared to be non-superior compared to heparin in
      reducing all-cause mortality, myocardial infarction, revascularisation, and
      stroke. Bivalirudin appeared to be related to a higher risk of stent thrombosis
      when compared to heparin plus provisional use of a glycoprotein IIb/IIIa
      inhibitor (GPI) at day 30 (RR 1.94 [1.16, 3.24] p < 0.01). Overall, bivalirudin
      based regimens present a lesser risk of major bleeding (RR 0.56 [0.44-0.71] p <
      0.001), and Thrombolysis In Myocardial Infarction (TIMI) major bleeding (RR 0.56
      [0.43-0.73]) compared with heparin-based regimens either with provisional or
      routine use of a GPI. However, the magnitude of TIMI major bleeding effect varied
      greatly (p < 0.001), depending on whether a GPI was provisionally used (RR 0.42
      [0.34-0.52] p < 0.001) or routinely used (RR 0.60 [0.43 -0.83] p < 0.001), in the
      heparin arm. This meta-analysis demonstrated that bivalirudin is associated with
      a lower risk of major bleeding, but a higher risk of stent thrombosis compared to
      heparin.

PMID- 28744216
TI  - Nuclear Magnetic Resonance-Based Metabolomics Approach to Evaluate the Prevention
      Effect of Camellia nitidissima Chi on Colitis-Associated Carcinogenesis.
AB  - Colorectal cancer (CRC) is one of the most common malignant tumors worldwide,
      occurring in the colon or rectum portion of large intestine. With marked
      antioxidant, anti-inflammation and anti-tumor activities, Camellia nitidissima
      Chi has been used as an effective treatment of cancer. The azoxymethane/dextran
      sodium sulfate (AOM/DSS) induced CRC mice model was established and the
      prevention effect of C. nitidissima Chi extracts on the evolving of CRC was
      evaluated by examination of neoplastic lesions, histopathological inspection,
      serum biochemistry analysis, combined with nuclear magnetic resonance (NMR)-based
      metabolomics and correlation network analysis. C. nitidissima Chi extracts could
      significantly inhibit AOM/DSS induced CRC, relieve the colonic pathology of
      inflammation and ameliorate the serum biochemistry, and could significantly
      reverse the disturbed metabolic profiling toward the normal state. Moreover, the
      butanol fraction showed a better efficacy than the water-soluble fraction of C.
      nitidissima Chi. Further development of C. nitidissima Chi extracts as a potent
      CRC inhibitor was warranted.

PMID- 28744218
TI  - Bioconcentration and Metabolism of Emodin in Zebrafish Eleutheroembryos.
AB  - Emodin is a major active anthraquinone of various herbal laxatives, which can
      exert many pharmacological effects. However, chronic use of anthranoid laxatives,
      even at low dosages, may cause melanosis coli (MC). It has been suggested that
      the accumulation of anthraquinones is a risk factor in the MC process. To
      investigate the accumulation of emodin, we conducted a bioconcentration study of
      emodin in zebrafish eleutheroembryos. Based on the economic cooperation and
      development (OECD) 305 test, zebrafish eleutheroembryos were exposed to emodin at
      a constant concentration for 48 h, before the test media were replaced by the
      blank medium for 24 h of depuration. To eliminate the effect of metabolism of
      emodin for assessment of the bioconcentration factor (BCF), we also conducted a
      modified test for which zebrafish eleutheroembryos were exposed to the non
      renewed test media, whose emodin concentration decreased with time. At different
      exposure time points, zebrafish eleutheroembryos and exposure media were sampled
      for analysis of emodin concentration using HPLC-MS/MS. The results showed rapid
      accumulation of emodin in zebrafish eleutheroembryos to reach a steady-state
      concentration within 24 h. Meanwhile, emodin was actively metabolized by
      zebrafish eleutheroembryos to result in 29.5-40.7% of its elimination. In the
      groups with high or low concentrations of emodin, the standardized BCF (sBCF)
      values in the standard test were 24.0 and 20.0, while those in the modified test
      were 50.4 and 52.0. These results showed that emodin could accumulate in
      zebrafish eleutheroembryos when used for 48 h and beyond, suggesting that the
      accumulation of anthraquinones may be a risk factor in the MC process.
      Accordingly, emodin should be unsuitable for long-term use due to its
      accumulation.

PMID- 28744217
TI  - The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence
      of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative
      Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation.
AB  - Hemorrhagic cystitis (HC) is one of the complications of busulfan
      cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic
      stem cell transplantation (HSCT) in children. Identifying children at high risk
      of developing HC in a HSCT setting could facilitate the evaluation and
      implementation of effective prophylactic measures. In this retrospective analysis
      genotyping of selected candidate gene variants was performed in 72 children and
      plasma Sulfolane (Su, water soluble metabolite of BU) levels were measured in 39
      children following treatment with BU-CY regimen. The cytotoxic effects of Su and
      acrolein (Ac, water soluble metabolite of CY) were tested on human urothelial
      cells (HUCs). The effect of Su was also tested on cytochrome P 450 (CYP) function
      in HepaRG hepatic cells. Cumulative incidences of HC before day 30 post HSCT were
      estimated using Kaplan-Meier curves and log-rank test was used to compare the
      difference between groups in a univariate analysis. Multivariate Cox regression
      was used to estimate hazard ratios with 95% confidence intervals (CIs).
      Multivariate analysis included co-variables that were significantly associated
      with HC in a univariate analysis. Cumulative incidence of HC was 15.3%. In the
      univariate analysis, HC incidence was significantly (p < 0.05) higher in children
      older than 10 years (28.6 vs. 6.8%) or in children with higher Su levels (>40 vs.
      <11%) or in carriers of both functional GSTM1 and CYP2C9 (33.3 vs. 6.3%) compared
      to the other group. In a multivariate analysis, combined GSTM1 and CYP2C9
      genotype status was associated with HC occurrence with a hazards ratio of 4.8
      (95% CI: 1.3-18.4; p = 0.02). Ac was found to be toxic to HUC cells at lower
      concentrations (33 MUM), Su was not toxic to HUC cells at concentrations below 1
      mM and did not affect CYP function in HepaRG cells. Our observations suggest that
      pre-emptive genotyping of CYP2C9 and GSTM1 may aid in selection of more effective
      prophylaxis to reduce HC development in pediatric patients undergoing allogeneic
      HSCT. Article summary: (1) Children carrying functional alleles in GSTM1 and
      CYP2C9 are at high risk for developing hemorrhagic cystitis following treatment
      with busulfan and cyclophosphamide based conditioning regimen. (2) Identification
      of children at high risk for developing hemorrhagic cystitis in an allogeneic
      HSCT setting will enable us to evaluate and implement optimal strategies for its
      prevention. Trial registration: This study is a part of the trail
      "clinicaltrials.gov identifier: NCT01257854."

PMID- 28744219
TI  - MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor.
AB  - Previous research has shown that a single dose of MDMA induce a dissociative
      state, by elevating feelings of depersonalization and derealization. Typically,
      it is assumed that action on the 5-HT2A receptor is the mechanism underlying
      these psychedelic experiences. In addition, other studies have shown associations
      between dissociative states and biological parameters (heart rate, cortisol),
      which are elevated by MDMA. In order to investigate the role of the 5-HT2
      receptor in the MDMA-induced dissociative state and the association with
      biological parameters, a placebo-controlled within-subject study was conducted
      including a single oral dose of MDMA (75 mg), combined with placebo or a single
      oral dose of the 5-HT2 receptor blocker ketanserin (40 mg). Twenty healthy
      recreational MDMA users filled out a dissociative states scale (CADSS) 90 min
      after treatments, which was preceded and followed by assessment of a number of
      biological parameters (cortisol levels, heart rate, MDMA blood concentrations).
      Findings showed that MDMA induced a dissociative state but this effect was not
      counteracted by pre-treatment with ketanserin. Heart rate was the only biological
      parameter that correlated with the MDMA-induced dissociative state, but an
      absence of correlation between these measures when participants were pretreated
      with ketanserin suggests an absence of directional effects of heart rate on
      dissociative state. It is suggested that the 5-HT2 receptor does not mediate the
      dissociative effects caused by a single dose of MDMA. Further research is needed
      to determine the exact neurobiology underlying this effect and whether these
      effects contribute to the therapeutic potential of MDMA.

PMID- 28744220
TI  - Rosmarinic Acid Protects against Inflammation and Cardiomyocyte Apoptosis during
      Myocardial Ischemia/Reperfusion Injury by Activating Peroxisome Proliferator
      Activated Receptor Gamma.
AB  - The cardiac ischemia-reperfusion (I/R) injury greatly influences the therapeutic
      effect and remains an urgent challenge in clinical therapy. Polypharmacology
      opens a new therapeutic opportunity to design drugs with a specific target for
      improving the efficacy. In this study, we first forecasted that Rosmarinic acid
      (RosA) could be used for the treatment of cardiovascular disease using text
      mining, chemometric and chemogenomic methods. Consistent with the effect of the
      positive drug (pioglitazone, PIO), we subsequently validated that RosA
      pretreatment could restore the decreased cardiac hemodynamic parameters (LVDP, +/
      dp/dtmin, +/- dp/dtmax and CF), decreased the infarct size and the cardiomyocyte
      apoptosis in a rat model of cardiac I/R injury. Furthermore, RosA pre-treatment
      inhibited the levels of inflammatory cytokines (IL-6, TNF-alpha and CRP), up
      regulated PPARgamma expression and down-regulated NF-kappaB expression in
      myocardial tissue isolated from the rat model of I/R-induced myocardial injury.
      In addition, the effects of RosA were reversed by co-treatment with PPAR-gamma
      inhibitor GW9662 and T0070907, respectively. These data suggest that RosA
      attenuates cardiac injury through activating PPARgamma and down-regulating NF
      kappaB-mediated signaling pathway, which inhibiting inflammation and
      cardiomyocyte apoptosis in a rat model of cardiac I/R injury.

PMID- 28744221
TI  - Sexual Dimorphism in the Age-Induced Insulin Resistance, Liver Steatosis, and
      Adipose Tissue Function in Rats.
AB  - Age-linked metabolic disturbances, such as liver steatosis and insulin
      resistance, show greater prevalence in men than in women. Thus, our aim was to
      analyze these sex-related differences in male and female Wistar rats (aged 26
      days and 3, 7, and 14 months), and to assess their potential relationship with
      alterations in the capacity of adipose tissue expansion and the dysregulation of
      the main adipokines produced by the adipose tissue, leptin and adiponectin.
      Adiposity-related parameters, blood parameters, the expression of genes related
      to expandability and inflammation (WAT), lipid metabolism (liver), and leptin and
      insulin signaling (both tissues) were measured. In females, adiposity index and
      WAT DNA content gradually increased with age, whereas males peaked at 7 months. A
      similar sex-dependent pattern was observed for leptin expression in WAT, while
      Mest expression levels decreased with age in males but not in females. Females
      also showed increased expression of the proliferation marker PCNA in the inguinal
      WAT compared to males. In males, leptin/adiponectin ratio greatly increased from
      7 to 14 months in a more acute manner than in females, along with an increase in
      HOMA-IR index and hepatic triacylglyceride content, while no changes were
      observed in females. In liver, 14-month-old males displayed decreased mRNA levels
      of Insr, Ampkalpha2, and Cpt1a compared with levels at 7 months. Males also
      showed decreased mRNA levels of Obrb (both tissues), and increased expression
      levels of Cd68 and Emr1 (WAT) with age. In conclusion, females are more protected
      from age-related metabolic disturbances, such as insulin resistance, hepatic
      lipid deposition, and WAT inflammation compared to males. This may be related to
      their greater capacity for WAT expansion-reflected by a greater Mest/leptin mRNA
      ratio-and to their ability to maintain adiponectin levels and preserve leptin
      sensitivity with aging.

PMID- 28744222
TI  - Presence of Functional Neurotrophin TrkB Receptors in the Rat Superior Cervical
      Ganglion.
AB  - Sympathetic neurons express the neurotrophin receptors TrkA, p75NTR, and a non
      functional truncated TrkB isoform (TrkB-Tc), but are not thought to express a
      functional full-length TrkB receptor (TrkB-Fl). We, and others, have demonstrated
      that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF)
      modulate synaptic transmission and synaptic plasticity in neurons of the superior
      cervical ganglion (SCG) of the rat. To clarify whether TrkB is expressed in
      sympathetic ganglia and contributes to the effects of BDNF upon sympathetic
      function, we characterized the presence and activity of the neurotrophin
      receptors expressed in the adult SCG compared with their presence in neonatal and
      cultured sympathetic neurons. Here, we expand our previous study regarding the
      immunodetection of neurotrophin receptors. Immunohistochemical analysis revealed
      that 19% of adult ganglionic neurons expressed TrkB-Fl immunoreactivity (IR), 82%
      expressed TrkA-IR, and 51% expressed p75NTR-IR; TrkB-Tc would be expressed in 36%
      of neurons. In addition, using Western-blotting and reverse transcriptase
      polymerase chain reaction (RT-PCR) analyses, we confirmed the expression of TrkB
      Fl and TrkB-Tc protein and mRNA transcripts in adult SCG. Neonatal neurons
      expressed significantly more TrkA-IR and TrkB-Fl-IR than p75NTR-IR. Finally, the
      application of neurotrophin, and high frequency stimulation, induced the
      activation of Trk receptors and the downstream PI3-kinase (phosphatidyl inositol
      3-kinase) signaling pathway, thus evoking the phosphorylation of Trk and Akt.
      These results demonstrate that SCG neurons express functional TrkA and TrkB-Fl
      receptors, which may contribute to the differential modulation of synaptic
      transmission and long-term synaptic plasticity.

PMID- 28744223
TI  - Modulation of the Plasma Kallikrein-Kinin System Proteins Performed by Heparan
      Sulfate Proteoglycans.
AB  - Human plasma kallikrein-kinin system proteins are related to inflammation through
      bradykinin. In the proximity of its target cells, high molecular weight kininogen
      (H-kininogen) is the substrate of plasma kallikrein, which releases bradykinin
      from H-kininogen. Heparan sulfate proteoglycans (HSPGs) play a critical role in
      either recruiting kinin precursors from the plasma, or in the assembly of
      kallikrein-kinin system components on the cell surface. Furthermore, HSPGs
      mediate the endocytosis and activation of H-kininogen and plasma prekallikrein.
      In the presence of HSPGs (Chinese hamster ovary cell, CHO-K1, wild type cells)
      both heparin and heparan sulfate strongly inhibit the H-kininogen interaction
      with the cell membrane. H-kininogen is internalized in endosomal acidic vesicles
      in CHO-K1 but not in CHO-745 cells (mutant cells deficient in glycosaminoglycan
      biosynthesis). The endocytosis process is lipid raft-mediated and is dependent on
      caveolae. Both types of CHO cells do not internalize bradykinin-free H-kininogen.
      At pH 7.35, bradykinin is released from H-kininogen on the surface of CHO-745
      cells only by serine proteases; however, in CHO-K1 cells either serine or
      cysteine proteases are found to be involved. The CHO-K1 cell lysate contains
      different kininogenases. Plasma prekallikrein endocytosis in CHO-K1 cells is
      independent of H-kininogen, and also prekallikrein is not internalized by CHO-745
      cells. Plasma prekallikrein cleavage/activation is independent of
      glycosaminoglycans but plasma kallikrein formation is more specific on H
      kininogen assembled on the cell surface through glycosaminoglycans. In this mini
      review, the importance of HSPGs in the regulation of plasma kallikrein-kinin
      system proteins is shown.

PMID- 28744224
TI  - Downregulated Translation Initiation Signaling Predisposes Low-Birth-Weight
      Neonatal Pigs to Slower Rates of Muscle Protein Synthesis.
AB  - Low-birth-weight (LBWT) neonates experience restricted muscle growth in their
      perinatal life. Our aim was to investigate the mechanisms that contribute to
      slower skeletal muscle growth of LBWT neonatal pigs. Twenty-four 1-day old male
      LBWT (816 +/- 55 g) and normal-birth-weight (NBWT; 1,642 +/- 55 g) littermates (n
      = 12) were euthanized to collect blood and longissimus dorsi (LD) muscle
      subsamples. Plasma glucose, insulin, and insulin-like growth factor-I (IGF-I)
      were lower in LBWT compared with NBWT pigs. Muscle IGF-I mRNA expression were
      lower in LBWT than NBWT pigs. However, IGF-I receptor mRNA and protein abundance
      was greater in LD of LBWT pigs. Abundance of myostatin and its receptors, and
      abundance and phosphorylation of smad3 were lower in LBWT LD by comparison with
      NBWT LD. Abundance of eukaryotic initiation factor (eIF) 4E binding protein 1 and
      mitogen-activated protein kinase-interacting kinases was lower in muscle of LBWT
      pigs compared with NBWT siblings, while eIF4E abundance and phosphorylation did
      not differ between the two groups. Furthermore, phosphorylation of ribosomal
      protein S6 kinase 1 (S6K1) was less in LBWT muscle, possibly due to lower eIF3e
      abundance. In addition, abundance and phosphorylation of eIF4G was reduced in
      LBWT pigs by comparison with NBWT littermates, suggesting translation initiation
      complex formation is compromised in muscle of LBWT pigs. In conclusion,
      diminished S6K1 activation and translation initiation signaling are likely the
      major contributors to impaired muscle growth in LBWT neonatal pigs. The
      upregulated IGF-I R expression and downregulated myostatin signaling seem to be
      compensatory responses for the reduction in protein synthesis signaling.

PMID- 28744226
TI  - The Mucosal Immune Function Is Not Compromised during a Period of High-Intensity
      Interval Training. Is It Time to Reconsider an Old Assumption?
AB  - Purpose: The aim of the study was to evaluate the mucosal immune function and
      circadian variation of salivary cortisol, Immunoglobin-A (sIgA) secretion rate
      and mood during a period of high-intensity interval training (HIIT) compared to
      long-slow distance training (LSD). Methods: Recreational male runners (n = 28)
      completed nine sessions of either HIIT or LSD within 3 weeks. The HIIT involved 4
      * 4 min of running at 90-95% of maximum heart rate interspersed with 3 min of
      active recovery while the LSD comprised of continuous running at 70-75% of
      maximum heart rate for 60-80 min. The psycho-immunological stress-response was
      investigated with a full daily profile of salivary cortisol and immunoglobin-A
      (sIgA) secretion rate along with the mood state on a baseline day, the first and
      last day of training and at follow-up 4 days after the last day of training.
      Before and after the training period, each athlete's running performance and peak
      oxygen uptake (V.O2peak) was determined with an incremental exercise test.
      Results: The HIIT resulted in a longer time-to-exhaustion (P = 0.02) and
      increased V.O2peak compared to LSD (P = 0.01). The circadian variation of sIgA
      secretion rate showed highest values in the morning immediately after waking up
      followed by a decrease throughout the day in both groups (P < 0.05). With HIIT,
      the wake-up response of sIgA secretion rate was higher on the last day of
      training (P < 0.01) as well as the area under the curve (AUCG) higher on the
      first and last day of training and follow-up compared to the LSD (P = 0.01). Also
      the AUCG for the sIgA secretion rate correlated with the increase in V.O2peak and
      running performance. The AUCG for cortisol remained unaffected on the first and
      last day of training but increased on the follow-up day with both, HIIT and LSD
      (P < 0.01). Conclusion: The increased sIgA secretion rate with the HIIT indicates
      no compromised mucosal immune function compared to LSD and shows the functional
      adaptation of the mucosal immune system in response to the increased stress and
      training load of nine sessions of HIIT.

PMID- 28744225
TI  - Is It Time to Begin a Public Campaign Concerning Frailty and Pre-frailty? A
      Review Article.
AB  - Frailty is a state that encompasses losses in physical, psychological or social
      domains. Therefore, frail people demonstrate a reduced potential to manage
      external stressors and to respond to life incidents. Consequently, such persons
      are prone to various adverse consequences such as falls, cognitive decline,
      infections, hospitalization, disability, institutionalization, and death. Pre
      frailty is a condition predisposing and usually preceding the frailty state.
      Early detection of frailty (i.e., pre-frailty) may present an opportunity to
      introduce effective management to improve outcomes. Exercise training appears to
      be the basis of such management in addition to periodic monitoring of food intake
      and body weight. However, various nutritional supplements and other probable
      interventions, such as treatment with vitamin D or androgen, require further
      investigation. Notably, many societies are not conscious of frailty as a health
      problem. In fact, people generally do not realize that they can change this
      unfavorable trajectory to senility. As populations age, it is reasonable to begin
      treating frailty similarly to other population-affecting disorders (e.g.,
      obesity, diabetes or cardiovascular diseases) and implement appropriate
      preventative measures. Social campaigns should inform societies about age-related
      frailty and pre-frailty and suggest appropriate lifestyles to avoid or delay
      these conditions. In this article, we review current information concerning
      therapeutic interventions in frailty and pre-frailty and discuss whether a
      greater public awareness of such conditions and some preventative and therapeutic
      measures may decrease their prevalence.

PMID- 28744227
TI  - Trauma of the Frontal Region Is Influenced by the Volume of Frontal Sinuses. A
      Finite Element Study.
AB  - Anatomy of frontal sinuses varies individually, from differences in volume and
      shape to a rare case when the sinuses are absent. However, there are scarce data
      related to influence of these variations on impact generated fracture pattern.
      Therefore, the aim of this study was to analyse the influence of frontal sinus
      volume on the stress distribution and fracture pattern in the frontal region. The
      study included four representative Finite Element models of the skull. Reference
      model was built on the basis of computed tomography scans of a human head with
      normally developed frontal sinuses. By modifying the reference model, three
      additional models were generated: a model without sinuses, with hypoplasic, and
      with hyperplasic sinuses. A 7.7 kN force was applied perpendicularly to the
      forehead of each model, in order to simulate a frontal impact. The results
      demonstrated that the distribution of impact stress in frontal region depends on
      the frontal sinus volume. The anterior sinus wall showed the highest fragility in
      case with hyperplasic sinuses, whereas posterior wall/inner plate showed more
      fragility in cases with hypoplasic and undeveloped sinuses. Well-developed
      frontal sinuses might, through absorption of the impact energy by anterior wall,
      protect the posterior wall and intracranial contents.

PMID- 28744228
TI  - Adolescent Major Depressive Disorder: Neuroimaging Evidence of Sex Difference
      during an Affective Go/No-Go Task.
AB  - Compared to female major depressive disorder (MDD), male MDD often receives less
      attention. However, research is warranted since there are significant sex
      differences in the clinical presentation of MDD and a higher rate of suicide in
      depressed men. To the best of our knowledge, this is the first functional
      magnetic resonance imaging (fMRI) study with a large sample addressing putative
      sex differences in MDD during adolescence, a period when one of the most robust
      findings in psychiatric epidemiology emerges; that females are twice as likely to
      suffer from MDD than males. Twenty-four depressed and 10 healthy male
      adolescents, together with 82 depressed and 24 healthy female adolescents, aged
      11-18 years, undertook an affective go/no-go task during fMRI acquisition. In
      response to sad relative to neutral distractors, significant sex differences (in
      the supramarginal gyrus) and group-by-sex interactions (in the supramarginal
      gyrus and the posterior cingulate cortex) were found. Furthermore, in contrast to
      the healthy male adolescents, depressed male adolescents showed decreased
      activation in the cerebellum with a significant group-by-age interaction in
      connectivity. Future research may consider altered developmental trajectories and
      the possible implications of sex-specific treatment and prevention strategies for
      MDD.

PMID- 28744229
TI  - Ultra-High-Field Magnetic Resonance Spectroscopy in Psychiatry.
AB  - The advantages of ultra-high-field (UHF >= 7T) MR have been demonstrated in a
      variety of MR acquisition modalities. Magnetic resonance spectroscopy (MRS) can
      particularly benefit from substantial gains in signal-to-noise ratio (SNR) and
      spectral resolution at UHF, enabling the quantification of numerous metabolites,
      including glutamate, glutamine, glutathione, and gamma-aminobutyric acid that are
      relevant to psychiatric disorders. The aim of this review is to give an overview
      about the advantages and advances of UHF MRS and its application to psychiatric
      disorders. In order to provide a practical guide for potential applications of
      MRS at UHF, a literature review is given, surveying advantages and disadvantages
      of MRS at UHF. Key concepts, emerging technologies, practical considerations, and
      applications of UHF MRS are provided. Second, the strength of UHF MRS is
      demonstrated using some examples of its application in psychiatric disorders.

PMID- 28744230
TI  - Primary Sjogren's Syndrome Associated With Treatment-Resistant Obsessive
      Compulsive Disorder.
AB  - There is an increasing awareness that autoimmune diseases can present with
      neuropsychiatric manifestations. We present the case of a 17-year-old female
      requiring psychiatric hospitalization for obsessive-compulsive disorder and major
      depressive disorder with mixed affective features, who was subsequently diagnosed
      with primary Sjogren's syndrome. Treatment with potent immunosuppression resulted
      in remission of psychiatric illness. Due to a lack of awareness and/or the lack
      of specific biomarkers, clinicians may not associate psychiatric symptoms with
      autoimmune disease, including primary Sjogren's syndrome. This case demonstrates
      that Sjogren's syndrome may be a causative or aggravating factor in mental
      disorders and that autoimmune diseases should be carefully considered in the
      differential diagnosis of psychiatric illness especially in cases of concurrent
      physical symptomatology and severity or treatment resistance of psychiatric
      disease.

PMID- 28744231
TI  - Understanding and Modeling Teams As Dynamical Systems.
AB  - By its very nature, much of teamwork is distributed across, and not stored
      within, interdependent people working toward a common goal. In this light, we
      advocate a systems perspective on teamwork that is based on general coordination
      principles that are not limited to cognitive, motor, and physiological levels of
      explanation within the individual. In this article, we present a framework for
      understanding and modeling teams as dynamical systems and review our empirical
      findings on teams as dynamical systems. We proceed by (a) considering the
      question of why study teams as dynamical systems, (b) considering the meaning of
      dynamical systems concepts (attractors; perturbation; synchronization; fractals)
      in the context of teams, (c) describe empirical studies of team coordination
      dynamics at the perceptual-motor, cognitive-behavioral, and cognitive
      neurophysiological levels of analysis, and (d) consider the theoretical and
      practical implications of this approach, including new kinds of explanations of
      human performance and real-time analysis and performance modeling. Throughout our
      discussion of the topics we consider how to describe teamwork using equations
      and/or modeling techniques that describe the dynamics. Finally, we consider what
      dynamical equations and models do and do not tell us about human performance in
      teams and suggest future research directions in this area.

PMID- 28744232
TI  - Production and Comprehension of Pantomimes Used to Depict Objects.
AB  - Pantomime, gesture in absence of speech, has no conventional meaning.
      Nevertheless, individuals seem to be able to produce pantomimes and derive
      meaning from pantomimes. A number of studies has addressed the use of co-speech
      gesture, but little is known on pantomime. Therefore, the question of how people
      construct and understand pantomimes arises in gesture research. To determine how
      people use pantomimes, we asked participants to depict a set of objects using
      pantomimes only. We annotated what representation techniques people produced.
      Furthermore, using judgment tasks, we assessed the pantomimes' comprehensibility.
      Analyses showed that similar techniques were used to depict objects across
      individuals. Objects with a default depiction method were better comprehended
      than objects for which there was no such default. More specifically, tools and
      objects depicted using a handling technique were better understood. The open
      answer experiment showed low interpretation accuracy. Conversely, the forced
      choice experiment showed ceiling effects. These results suggest that across
      individuals, similar strategies are deployed to produce pantomime, with the
      handling technique as the apparent preference. This might indicate that the
      production of pantomimes is based on mental representations which are
      intrinsically similar. Furthermore, pantomime conveys semantically rich, but
      ambiguous, information, and its interpretation is much dependent on context. This
      pantomime database is available online:
      https://dataverse.nl/dataset.xhtml?persistentId=hdl:10411/QZHO6M. This can be
      used as a baseline with which we can compare clinical groups.

PMID- 28744233
TI  - Vocal Features of Song and Speech: Insights from Schoenberg's Pierrot Lunaire.
AB  - Similarities and differences between speech and song are often examined. However,
      the perceptual definition of these two types of vocalization is challenging.
      Indeed, the prototypical characteristics of speech or song support top-down
      processes, which influence listeners' perception of acoustic information. In
      order to examine vocal features associated with speaking and singing, we propose
      an innovative approach designed to facilitate bottom-up mechanisms in perceiving
      vocalizations by using material situated between speech and song: Speechsong. 25
      participants were asked to evaluate 20 performances of a speechsong composition
      by Arnold Schoenberg, "Pierrot lunaire" op. 21 from 1912, evaluating 20 features
      of vocal-articulatory expression. Raters provided reliable judgments concerning
      the vocal features used by the performers and did not show strong appeal or
      specific expectations in reference to Schoenberg's piece. By examining the
      relationship between the vocal features and the impression of song or speech, the
      results confirm the importance of pitch (height, contour, range), but also point
      to the relevance of register, timbre, tension and faucal distance. Besides
      highlighting vocal features associated with speech and song, this study supports
      the relevance of the present approach of focusing on a theoretical middle
      category in order to better understand vocal expression in song and speech.

PMID- 28744234
TI  - On "Hearing" Voices and "Seeing" Things: Probing Hallucination Predisposition in
      a Portuguese Nonclinical Sample with the Launay-Slade Hallucination Scale
      Revised.
AB  - The experience of hallucinations is a hallmark of psychotic disorders, but they
      are also present in other psychiatric and medical conditions, and may be reported
      in nonclinical individuals. Despite the increased number of studies probing the
      incidence of nonclinical hallucinations, the underlying phenomenological
      characteristics are still poorly understood. This study aimed to examine the
      psychometrics proprieties of the Portuguese adaptation of the 16-item Launay
      Slade Hallucinations Scale (LSHS), the phenomenological characteristics of
      nonclinical hallucinatory experiences in a Portuguese sample, and the
      relationship between clinical symptoms and hallucination predisposition. Three
      hundred-and-fifty-four European Portuguese college students completed the LSHS.
      Of those, 16 participants with high LSHS scores and 14 with low LSHS scores were
      further screened for clinical symptoms. A three-factor solution for the LSHS
      Portuguese version proved to be the most adequate. Intrusive or vivid thoughts
      and sleep-related hallucinations were the most common. Although, fundamentally
      perceived as positive experiences, all types of hallucinations were described as
      uncontrollable and dominating. However, the more pleasant they were perceived,
      the more controllable they were assessed. In addition, hallucination
      predisposition was associated with increased clinical symptoms. These results
      corroborate the lower severity of hallucinations in the general population
      compared to psychotic individuals. Further, they support an association between
      clinical symptoms and increased vulnerability to hallucinations. Specifically,
      increased schizotypal tendencies and negative mood (anxiety and depression) may
      be related to increased psychotic risk.

PMID- 28744235
TI  - Big Hitters: Important Factors Characterizing Team Effectiveness in Professional
      Cricket.
AB  - While organizational psychology attests to the multidimensional nature of team
      effectiveness, insight regarding the most important factors contributing to the
      effectiveness of sports teams, especially elite teams, is lacking. An abductive
      method of qualitative enquiry was adopted to capture participants' construal of
      team effectiveness, drawing on the extant literature in both sport and
      organizational psychology. Semi-structured interviews were conducted with 21
      players, coaches, and psychologists involved in elite cricket, with resultant
      data analyzed inductively initially, before being reanalyzed deductively.
      Although, the narratives endorsed the value of many of the deductively derived
      factors, other constructs more prominent in organizational psychology (e.g.,
      trust and intra-group conflict) appeared to be more important than traditional
      sport psychology group factors. The results revealed six broad themes; culture
      and environment, values, communication, understanding, leadership, and unique
      individuals, with some gender differences apparent throughout. Based on our elite
      sample's construal of team effectiveness, we propose a new model representing a
      practical, parsimonious, and novel conceptualization of the most important
      attributes of team effectiveness in cricket, with conceivable transferability to
      other team sports.

PMID- 28744237
TI  - Editorial: How do Emotions and Feelings Regulate Physical Activity?

PMID- 28744236
TI  - Trimodal Race Model Inequalities in Multisensory Integration: I. Basics.
AB  - The race model inequality has become an important testing tool for the analysis
      of redundant signals tasks. In crossmodal reaction time experiments, the strength
      of violation of the inequality is taken as measure of multisensory integration
      occurring beyond probability summation. Here we extend previous results on
      trimodal race model inequalities and specify the underlying context invariance
      assumptions required for their validity. Some simulation results comparing the
      race model and the superposition model for Erlang distributed random variables
      illustrate the trimodal inequalities.

PMID- 28744238
TI  - Long-Term Prognostic Validity of Talent Selections: Comparing National and
      Regional Coaches, Laypersons and Novices.
AB  - In most sports, the development of elite athletes is a long-term process of
      talent identification and support. Typically, talent selection systems administer
      a multi-faceted strategy including national coach observations and varying
      physical and psychological tests when deciding who is chosen for talent
      development. The aim of this exploratory study was to evaluate the prognostic
      validity of talent selections by varying groups 10 years after they had been
      conducted. This study used a unique, multi-phased approach. Phase 1 involved
      players (n = 68) in 2001 completing a battery of general and sport-specific tests
      of handball 'talent' and performance. In Phase 2, national and regional coaches
      (n = 7) in 2001 who attended training camps identified the most talented players.
      In Phase 3, current novice and advanced handball players (n = 12 in each group)
      selected the most talented from short videos of matches played during the talent
      camp. Analyses compared predictions among all groups with a best model-fit
      derived from the motor tests. Results revealed little difference between regional
      and national coaches in the prediction of future performance and little
      difference in forecasting performance between novices and players. The best model
      fit regression by the motor-tests outperformed all predictions. While several
      limitations are discussed, this study is a useful starting point for future
      investigations considering athlete selection decisions in talent identification
      in sport.

PMID- 28744239
TI  - Social and Cognitive Impressions of Adults Who Do and Do Not Stutter Based on
      Listeners' Perceptions of Read-Speech Samples.
AB  - Stuttering is a neurodevelopmental disorder characterized by frequent and
      involuntary disruptions during speech production. Adults who stutter are often
      subject to negative perceptions. The present study examined whether negative
      social and cognitive impressions are formed when listening to speech, even
      without any knowledge about the speaker. Two experiments were conducted in which
      naive participants were asked to listen to and provide ratings on samples of read
      speech produced by adults who stutter and typically-speaking adults without
      knowledge about the individuals who produced the speech. In both experiments,
      listeners rated speaker cognitive ability, likeability, anxiety, as well as a
      number of speech characteristics that included fluency, naturalness,
      intelligibility, the likelihood the speaker had a speech-and-language disorder
      (Experiment 1 only), rate and volume (both Experiments 1 and 2). The speech of
      adults who stutter was perceived to be less fluent, natural, intelligible, and to
      be slower and louder than the speech of typical adults. Adults who stutter were
      also perceived to have lower cognitive ability, to be less likeable and to be
      more anxious than the typical adult speakers. Relations between speech
      characteristics and social and cognitive impressions were found, independent of
      whether or not the speaker stuttered (i.e., they were found for both adults who
      stutter and typically-speaking adults) and did not depend on being cued that some
      of the speakers may have had a speech-language impairment.

PMID- 28744241
TI  - Commentary: Spontaneous expression of mirror self-recognition in monkeys after
      learning precise visual-proprioceptive association for mirror images.

PMID- 28744240
TI  - Altered Brain Activities Associated with Craving and Cue Reactivity in People
      with Internet Gaming Disorder: Evidence from the Comparison with Recreational
      Internet Game Users.
AB  - Although the neural substrates of cue reactivity in Internet gaming disorder
      (IGD) have been examined in previous studies, most of these studies focused on
      the comparison between IGD subjects and healthy controls, which cannot exclude a
      potential effect of cue-familiarity. To overcome this limitation, the current
      study focuses on the comparison between IGD subjects and recreational Internet
      game users (RGU) who play online games recreationally but do not develop
      dependence. Data from 40 RGU and 30 IGD subjects were collected while they were
      performing an event-related cue reactivity task in the fMRI scanner. The results
      showed that the IGD subjects were associated with enhanced activation in the left
      orbitofrontal cortex (OFC) and decreased activation in the right anterior
      cingulate cortex (ACC), right precuneus, left precentral gyrus and right
      postcentral gyrus in comparison with the RGU subjects. OFC is involved in reward
      evaluation and ACC is implicated in executive control function based on previous
      researches. Moreover, the activation of OFC were correlated with the desire for
      game-playing. Thus, the higher activation in OFC might suggests high desire for
      game playing, and the lower activation in ACC might indicates impaired ability in
      inhibiting the urge to gaming-related stimuli in IGD subjects. Additionally,
      decreased activation in the precuneus, the precentral and postcentral gyrus may
      suggest the deficit in disentangling from game-playing stimuli. These findings
      explain why IGD subjects develop dependence on game-playing while RGU subjects
      can play online games recreationally and prevent the transition from voluntary
      game-playing to eventually IGD.

PMID- 28744242
TI  - Complex Problem Solving: What It Is and What It Is Not.
AB  - Computer-simulated scenarios have been part of psychological research on problem
      solving for more than 40 years. The shift in emphasis from simple toy problems to
      complex, more real-life oriented problems has been accompanied by discussions
      about the best ways to assess the process of solving complex problems.
      Psychometric issues such as reliable assessments and addressing correlations with
      other instruments have been in the foreground of these discussions and have left
      the content validity of complex problem solving in the background. In this paper,
      we return the focus to content issues and address the important features that
      define complex problems.

PMID- 28744243
TI  - The Odyssey of Dental Anxiety: From Prehistory to the Present. A Narrative
      Review.
AB  - Dental anxiety (DA) can be considered as a universal phenomenon with a high
      prevalence worldwide; DA and pain are also the main causes for medical
      emergencies in the dental office, so their prevention is an essential part of
      patient safety and overall quality of care. Being DA and its consequences closely
      related to the fight-or-flight reaction, it seems reasonable to argue that the
      odyssey of DA began way back in the distant past, and has since probably evolved
      in parallel with the development of fight-or-flight reactions, implicit memory
      and knowledge, and ultimately consciousness. Basic emotions are related to
      survival functions in an inseparable psychosomatic unity that enable an immediate
      response to critical situations rather than generating knowledge, which is why
      many anxious patients are unaware of the cause of their anxiety. Archeological
      findings suggest that humans have been surprisingly skillful and knowledgeable
      since prehistory. Neanderthals used medicinal plants; and relics of dental tools
      bear witness to a kind of Neolithic proto-dentistry. In the two millennia BC,
      Egyptian and Greek physicians used both plants (such as papaver somniferum) and
      incubation (a forerunner of modern hypnosis, e.g., in the sleep temples dedicated
      to Asclepius) in the attempt to provide some form of therapy and painless
      surgery, whereas modern scientific medicine strongly understated the role of
      subjectivity and mind-body approaches until recently. DA has a wide range of
      causes and its management is far from being a matter of identifying the ideal
      sedative drug. A patient's proper management must include assessing his/her
      dental anxiety, ensuring good communications, and providing information
      (iatrosedation), effective local anesthesia, hypnosis, and/or a wise use of
      sedative drugs where necessary. Any weak link in this chain can cause avoidable
      suffering, mistrust, and emergencies, as well as having lifelong psychological
      consequences. Iatrosedation and hypnosis are no less relevant than drugs and
      should be considered as primary tools for the management of DA. Unlike
      pharmacological sedation, they allow to help patients cope with the dental
      procedure and also overcome their anxiety: achieving the latter may enable them
      to face future dental care autonomously, whereas pharmacological sedation can
      only afford a transient respite.

PMID- 28744244
TI  - Further Insight into the Effectiveness of a Behavioral Teacher Program Targeting
      ADHD Symptoms Using Actigraphy, Classroom Observations and Peer Ratings.
AB  - Objective: The Positivity and Rules program (PR program), a low-level behavioral
      teacher program targeting symptoms of attention-deficit/hyperactivity disorder
      (ADHD), has shown positive effects on teacher-rated ADHD symptoms and social
      functioning. This study aimed to assess whether program effects could be
      confirmed by instruments assessing classroom behavior other than teacher-ratings,
      given teachers' involvement with the training. Methods: Participants were 114
      primary school children (age = 6-13) displaying ADHD symptoms in the classroom,
      who were randomly assigned to the treatment (n = 58) or control group (n = 65).
      ADHD symptoms were measured using classroom observations and actigraphy, and peer
      acceptance was measured using peer ratings. Intention-to-treat multilevel
      analyses were conducted to assess program effects. Results: No beneficial program
      effects were found for any of the measures. Conclusion: The earlier beneficial
      program effects on both ADHD symptoms and social functioning reported by
      teachers, may be explained by a change in the perception of teachers rather than
      changes in the child's behavior. Other methodological explanations are also
      discussed, such as differences between instruments in the sensitivity to program
      related changes. The current study underlines the importance of using different
      measures of classroom behavior to study program effects. ClinicalTrials.gov
      registration number: NCT02518711.

PMID- 28744245
TI  - Distinguishing Relational Aspects of Character Strengths with Subjective and
      Psychological Well-being.
AB  - Research has shown that character strengths are positively linked with well-being
      in general. However, there has not been a fine-grained analysis up to date. This
      study examines the individual relational aspects between the 24 character
      strengths, subjective well-being (SWB), and different aspects of psychological
      well-being (PWB) at two times of measurement (N = 117). Results showed that
      overall the "good character" was significantly stronger related with PWB than
      with SWB. The character strength "hope" was at least moderately correlated with
      the PWB aspects meaning, optimism and autonomy, and "zest" with the PWB aspects
      relationships and engagement. "Persistence" showed the highest correlation with
      the PWB aspect mastery. Out of the 24 character strengths, the happiness-related
      strengths (hope, zest, gratitude, curiosity, and love) were more likely to
      correlate with PWB and SWB than any other character strength. This study offers a
      more fine-grained and thorough understanding of specific relational aspects
      between the 24 character strengths and a broad range of well-being aspects.
      Future studies should take up a detailed strategy when exploring relationships
      between character strengths and well-being.

PMID- 28744246
TI  - Predictors of Citation Rate in Psychology: Inconclusive Influence of Effect and
      Sample Size.
AB  - In the present article, we investigate predictors of how often a scientific
      article is cited. Specifically, we focus on the influence of two often neglected
      predictors of citation rate: effect size and sample size, using samples from two
      psychological topical areas. Both can be considered as indicators of the
      importance of an article and post hoc (or observed) statistical power, and
      should, especially in applied fields, predict citation rates. In Study 1, effect
      size did not have an influence on citation rates across a topical area, both with
      and without controlling for numerous variables that have been previously linked
      to citation rates. In contrast, sample size predicted citation rates, but only
      while controlling for other variables. In Study 2, sample and partly effect sizes
      predicted citation rates, indicating that the relations vary even between
      scientific topical areas. Statistically significant results had more citations in
      Study 2 but not in Study 1. The results indicate that the importance (or power)
      of scientific findings may not be as strongly related to citation rate as is
      generally assumed.

PMID- 28744247
TI  - How Do Cultural Factors Influence the Teaching and Practice of Mindfulness and
      Compassion in Latin Countries?

PMID- 28744248
TI  - Experience with the Cardinal Coordinate System Contributes to the Precision of
      Cognitive Maps.
AB  - The coordinate system has been proposed as a fundamental and cross-culturally
      used spatial representation, through which people code location and direction
      information in the environment. Here we provided direct evidence demonstrating
      that daily experience with the cardinal coordinate system (i.e., east, west,
      north, and south) contributed to the representation of cognitive maps.
      Behaviorally, we found that individuals who relied more on the cardinal
      coordinate system for daily navigation made smaller errors in an indoor pointing
      task, suggesting that the cardinal coordinate system is an important element of
      cognitive maps. Neurally, the extent to which individuals relied on the cardinal
      coordinate system was positively correlated with the gray matter volume of the
      entorhinal cortex, suggesting that the entorhinal cortex may serve as the
      neuroanatomical basis of coordinate-based navigation (the entorhinal coordinate
      area, ECA). Further analyses on the resting-state functional connectivity
      revealed that the intrinsic interaction between the ECA and two hippocampal sub
      regions, the subiculum and cornu ammonis, might be linked with the representation
      precision of cognitive maps. In sum, our study reveals an association between
      daily experience with the cardinal coordinate system and cognitive maps, and
      suggests that the ECA works in collaboration with hippocampal sub-regions to
      represent cognitive maps.

PMID- 28744249
TI  - Perceived Prejudice and the Mental Health of Chinese Ethnic Minority College
      Students: The Chain Mediating Effect of Ethnic Identity and Hope.
AB  - As a multinational country incorporating 56 officially recognized ethnic groups,
      China is concerned with the mental health of members of minority ethnic groups,
      with an increasing focus on supporting Chinese ethnic minority college students.
      Nevertheless, in daily life, members of minority ethnic groups in China often
      perceive prejudice, which may in turn negatively influence their mental health,
      with respect to relative levels of ethnic identity and hope. To examine the
      mediating effects of ethnic identity and hope on the relationship between
      perceived prejudice and the mental health of Chinese ethnic minority college
      students, 665 students (18-26 years old; 207 males, 458 females; the proportion
      of participants is 95.38%) from nine colleges in the Guangxi Zhuang autonomous
      region and Yunnan and Guizhou provinces of China took part in our study, each
      completing adapted versions of a perceived prejudice scale, a multiethnic
      identity measure, an adult dispositional hope scale, and a general health
      questionnaire. Analysis of the results reveals that perceived prejudice
      negatively influences mental health through both ethnic identity and hope in
      Chinese ethnic minority college students. The total mediation effect was 54.9%.
      Perceived prejudice was found to negatively predict ethnic identity and hope,
      suggesting that perceived prejudice brings about a negative reconstruction of
      ethnic identity and hope mechanisms within the study's Chinese cultural context.
      The relationship between perceived prejudice and mental health was fully mediated
      by hope and the chain of ethnic identity and hope. Ethnic identity partially
      mediated the relationship between perceived prejudice and hope. The relationship
      between perceived prejudice and mental health mediated by ethnic identity was not
      significant, which suggests that the rejection-identification model cannot be
      applied to Chinese ethnic minority college students. This paper concludes by
      considering the limitations of our study and discussing the implications of its
      results for researchers and practitioners.

PMID- 28744250
TI  - Bilateral Patterns of Repetitive Movements in 6- to 12-Month-Old Infants with
      Autism Spectrum Disorders.
AB  - Aim: Some patterns of repetitive movements and their frequency have been proved
      to distinguish infants with Autism Spectrum Disorders (ASD) from infants with
      Typical Development (TD) and Developmental Delay (DD) from 12 months of life on.
      The purpose of this study is to investigate if a specific repertoire of
      repetitive movements is present earlier in life, and if their higher rate and
      duration could differentiate infants with ASD from infants with DD and TD aged
      between 6 and 12 months. Method: We conducted a retrospective analysis of video
      clips taken from home videos to compare the frequency and the duration of
      Repetitive Movement Episodes (RMEs) in a sample of 30 children equally
      distributed among the three groups. Results: Significantly higher total scores in
      bilateral RMEs with arms, hands, fingers, and lower limbs were found to
      distinguish ASD infants from both DD and TD infants, with a satisfactory
      diagnostic efficiency. No significant difference was found between the
      distributions of unilateral RMEs between ASD and DD/TD. Interpretation: Results
      indicate the presence at this age of an ASD-specific pattern of bilateral
      repetitive movements. We hypothesize a continuum between this pattern and the
      lack of variability in finalized and communicative movements and gestures
      observed in children with ASD during the second year of life.

PMID- 28744251
TI  - Ethical Leadership, Leader-Member Exchange and Feedback Seeking: A Double
      Moderated Mediation Model of Emotional Intelligence and Work-Unit Structure.
AB  - This research elucidates the role of ethical leadership in employee feedback
      seeking by examining how and when ethical leadership may exert a positive
      influence on feedback seeking. Using matched reports from 64 supervisors and 265
      of their immediate employees from a hotel group located in a major city in China,
      we proposed and tested a moderated mediation model that examines leader-member
      exchange (LMX) as the mediator and emotional intelligence as well as work-unit
      structure as double moderators in the relationships between ethical leadership
      and followers' feedback-seeking behavior from supervisors and coworkers. Our
      findings indicated that (1) LMX mediated the positive relationship between
      ethical leadership and feedback seeking from both ethical leaders and coworkers,
      and (2) emotional intelligence and work-unit structure served as joint moderators
      on the mediated positive relationship in such a way that the relationship was
      strongest when the emotional intelligence was high and work-unit structure was
      more of an organic structure rather than a mechanistic structure.

PMID- 28744253
TI  - Novel Eye Movement Disorders in Whipple's Disease-Staircase Horizontal Saccades,
      Gaze-Evoked Nystagmus, and Esotropia.
AB  - Whipple's disease, a rare systemic infectious disorder, is complicated by the
      involvement of the central nervous system in about 5% of cases. Oscillations of
      the eyes and the jaw, called oculo-masticatory myorhythmia, are pathognomonic of
      the central nervous system involvement but are often absent. Typical
      manifestations of the central nervous system Whipple's disease are cognitive
      impairment, parkinsonism mimicking progressive supranuclear palsy with vertical
      saccade slowing, and up-gaze range limitation. We describe a unique patient with
      the central nervous system Whipple's disease who had typical features, including
      parkinsonism, cognitive impairment, and up-gaze limitation; but also had
      diplopia, esotropia with mild horizontal (abduction more than adduction)
      limitation, and vertigo. The patient also had gaze-evoked nystagmus and staircase
      horizontal saccades. Latter were thought to be due to mal-programmed small
      saccades followed by a series of corrective saccades. The saccades were
      disconjugate due to the concurrent strabismus. Also, we noted disconjugacy in the
      slow phase of gaze-evoked nystagmus. The disconjugacy of the slow phase of gaze
      evoked nystagmus was larger during monocular viewing condition. We propose that
      interaction of the strabismic drifts of the covered eyes and the nystagmus drift,
      putatively at the final common pathway might lead to such disconjugacy.

PMID- 28744252
TI  - Deficits in Approximate Number System Acuity and Mathematical Abilities in 6.5
      Year-Old Children Born Extremely Preterm.
AB  - Preterm children are at increased risk for poor academic achievement, especially
      in math. In the present study, we examined whether preterm children differ from
      term-born children in their intuitive sense of number that relies on an
      unlearned, approximate number system (ANS) and whether there is a link between
      preterm children's ANS acuity and their math abilities. To this end, 6.5-year-old
      extremely preterm (i.e., <27 weeks gestation, n = 82) and term-born children (n =
      89) completed a non-symbolic number comparison (ANS acuity) task and a
      standardized math test. We found that extremely preterm children had
      significantly lower ANS acuity than term-born children and that these differences
      could not be fully explained by differences in verbal IQ, perceptual reasoning
      skills, working memory, or attention. Differences in ANS acuity persisted even
      when demands on visuo-spatial skills and attention were reduced in the ANS task.
      Finally, we found that ANS acuity and math ability are linked in extremely
      preterm children, similar to previous results from term-born children. These
      results suggest that deficits in the ANS may be at least partly responsible for
      the deficits in math abilities often observed in extremely preterm children.

PMID- 28744254
TI  - Metabolic Characterization of a Novel RORalpha Knockout Mouse Model without
      Ataxia.
AB  - The retinoic acid receptor-related receptor alpha (RORalpha) is a nuclear
      receptor that plays an important role in regulation of metabolism and the immune
      system. Genetic deletion of the receptor yields mice with significant cerebellar
      developmental issues associated with severe ataxia. Although many metabolic
      studies have been performed in these models, the impaired locomotor activity of
      these mice is known to affect their normal mobility and feeding behaviors. This
      creates some difficulty in interpretation of the role of RORalpha in models of
      metabolic disease where feeding and muscle function is a critical component of
      the pathophysiology. We generated a mouse with a floxed Rora allele that we
      crossed with a mouse line expressing Cre recombinase under the control of the
      EIIa promoter to obtain a full body deletion of Rora. This cross led to a partial
      deletion of the Rora locus likely due to mosaic expression of the EIIa-Cre
      transgene. These mice lack any signs of ataxia but display an improved metabolic
      profile relative to normal WT mice. The mice were resistant to diet- and age
      induced metabolic syndrome and exhibited improved glucose tolerance and increased
      insulin sensitivity. Decreased RORalpha expression in the mice was also
      associated with reduced inflammation in models of metabolic syndrome. These data
      indicate that suppression of RORalpha activity improves metabolic function and
      reduces inflammation.

PMID- 28744255
TI  - Glycemic and Metabolic Effects of Two Long Bouts of Moderate-Intensity Exercise
      in Men with Normal Glucose Tolerance or Type 2 Diabetes.
AB  - BACKGROUND: The glycemic and insulinemic responses following 30-60 min of
      exercise have been extensively studied, and a dose-response has been proposed
      between exercise duration, or volume, and improvements in glucose tolerance or
      insulin sensitivity. However, few studies have examined the effects of longer
      bouts of exercise in type 2 diabetes (T2D). Longer bouts may have a greater
      potential to affect glucagon, interleukin-6 (IL-6) and incretin hormones [i.e.,
      glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide
      (GIP)]. AIM: To examine the effect of two bouts of long-duration, moderate
      intensity exercise on incretins, glucagon, and IL-6 responses before and after
      exercise, as well as in response to an oral glucose tolerance test (OGTT)
      conducted the following day. METHODS: Twelve men, six with and six without T2D,
      participated in two separate conditions (i.e., exercise vs. rest) according to a
      randomized crossover design. On day 1, participants either rested or performed
      two 90 min bouts of treadmill exercise (separated by 3.5 h) at 80% of their
      ventilatory threshold. All participants received standardized meals on day 1. On
      day 2 of each condition, glucose and hormonal responses were measured during a 4
      h OGTT. RESULTS: On day 1, exercise increased IL-6 at the end of the first bout
      of exercise (exercise by time interaction p = 0.03) and GIP overall (main effect
      of exercise p = 0.004). Glucose was reduced to a greater extent in T2D following
      exercise (exercise by T2D interaction p = 0.03). On day 2, GIP and active GLP-1
      were increased in the fasting state (p = 0.05 and p = 0.03, respectively), while
      plasma insulin and glucagon concentrations were reduced during the OGTT (p = 0.01
      and p = 0.02, respectively) in the exercise compared to the rest condition for
      both healthy controls and T2D. Postprandial glucose was elevated in T2D compared
      to healthy control (p < 0.05) but was not affected by exercise. CONCLUSION: Long
      duration, moderate-intensity aerobic exercise can increase IL-6. On the day
      following exercise, fasting incretins remained increased but postprandial insulin
      and glucagon were decreased without affecting postprandial glucose. This long
      duration of exercise may not be appropriate for some people, and further research
      should investigate why next day glucose tolerance was unchanged.

PMID- 28744256
TI  - Corticotropin-Releasing Hormone As the Homeostatic Rheostat of Feto-Maternal
      Symbiosis and Developmental Programming In Utero and Neonatal Life.
AB  - A balanced interaction between the homeostatic mechanisms of mother and the
      developing organism during pregnancy and in early neonatal life is essential in
      order to ensure optimal fetal development, ability to respond to various external
      and internal challenges, protection from adverse programming, and safeguard
      maternal care availability after parturition. In the majority of pregnancies,
      this relationship is highly effective resulting in successful outcomes. However,
      in a number of pathological settings, perturbations of the maternal homeostasis
      disrupt this symbiosis and initiate adaptive responses with unpredictable
      outcomes for the fetus or even the neonate. This may lead to development of
      pathological phenotypes arising from developmental reprogramming involving
      interaction of genetic, epigenetic, and environmental-driven pathways, sometimes
      with acute consequences (e.g., growth impairment) and sometimes delayed (e.g.,
      enhanced susceptibility to disease) that last well into adulthood. Most of these
      adaptive mechanisms are activated and controlled by hormones of the hypothalamo
      pituitary adrenal axis under the influence of placental steroid and peptide
      hormones. In particular, the hypothalamic peptide corticotropin-releasing hormone
      (CRH) plays a key role in feto-maternal communication by orchestrating and
      integrating a series of neuroendocrine, immune, metabolic, and behavioral
      responses. CRH also regulates neural networks involved in maternal behavior and
      this determines efficiency of maternal care and neonate interactions. This review
      will summarize our current understanding of CRH actions during the perinatal
      period, focusing on the physiological roles for both mother and offspring and
      also how external challenges can alter CRH actions and potentially impact on
      fetus/neonate health.

PMID- 28744257
TI  - Abundance and Distribution of Microbial Cells and Viruses in an Alluvial Aquifer.
AB  - Viruses are the most abundant biological entity on Earth and their interactions
      with microbial communities are recognized to influence microbial ecology and
      impact biogeochemical cycling in various ecosystems. While the factors that
      control the distribution of viruses in surface aquatic environments are well
      characterized, the abundance and distribution of continental subsurface viruses
      with respect to microbial abundance and biogeochemical parameters have not yet
      been established. In order to begin to understand the factors governing virus
      distribution in subsurface environments, we assessed microbial cell and virus
      abundance in groundwater concurrent with groundwater chemistry in a uranium
      impacted alluvial aquifer adjoining the Colorado River near Rifle, CO. Virus
      abundance ranged from 8.0 * 104 to 1.0 * 106 mL-1 and exceeded cell abundance in
      all samples (cell abundance ranged from 5.8 * 104 to 6.1 * 105 mL-1). The virus
      to microbial cell ratio ranged from 1.1 to 8.1 and averaged 3.0 +/- 1.6 with
      virus abundance most strongly correlated to cell abundance (Spearman's rho =
      0.73, p < 0.001). Both viruses and cells were positively correlated to dissolved
      organic carbon (DOC) with cells having a slightly stronger correlation
      (Spearman's rho = 0.46, p < 0.05 and rho = 0.54, p < 0.05; respectively).
      Groundwater uranium was also strongly correlated with DOC and virus and cell
      abundance (Spearman's rho = 0.62, p < 0.05; rho = 0.46, p < 0.05; and rho = 0.50,
      p < 0.05; respectively). Together the data indicate that microbial cell and virus
      abundance are correlated to the geochemical conditions in the aquifer. As such
      local geochemical conditions likely control microbial host cell abundance which
      in turn controls viral abundance. Given the potential impacts of viral-mediated
      cell lysis such as liberation of labile organic matter from lysed cells and
      changes in microbial community structure, viral interactions with the microbiota
      should be considered in an effort to understand subsurface biogeochemical cycling
      and contaminant mobility.

PMID- 28744258
TI  - Complete Genome Sequence of Streptococcus thermophilus KLDS 3.1003, A Strain with
      High Antimicrobial Potential against Foodborne and Vaginal Pathogens.
AB  - Lactic acid bacteria play increasingly important roles in the food industry.
      Streptococcus thermophilus KLDS 3.1003 strain was isolated from traditional
      yogurt in Inner Mongolia, China. It has shown high antimicrobial activity against
      selected foodborne and vaginal pathogens. In this study, we investigated and
      analyzed its complete genome sequence. The S. thermophilus KLDS 3.1003 genome
      comprise of a 1,899,956 bp chromosome with a G+C content of 38.92%, 1,995 genes,
      and 6 rRNAs. With the exception of S. thermophilus M17TZA496, S. thermophilus
      KLDS 3.1003 has more tRNAs (amino acid coding genes) compared to some S.
      thermophilus strains available on the National Centre for Biotechnology
      Information database. MG-RAST annotation showed that this strain has 317
      subsystems with most genes associated with amino acid and carbohydrate
      metabolism. This strain also has a unique EPS gene cluster containing 23 genes,
      and may be a mixed dairy starter culture. This information provides more insight
      into the molecular basis of its potentials for further applications in the dairy
      and allied industries.

PMID- 28744259
TI  - Development of Human Breast Milk Microbiota-Associated Mice as a Method to
      Identify Breast Milk Bacteria Capable of Colonizing Gut.
AB  - Human breast milk is recognized as one of multiple important sources of commensal
      bacteria for infant gut. Previous studies searched for the bacterial strains
      shared between breast milk and infant feces by isolating bacteria and performing
      strain-level bacterial genotyping, but only limited number of milk bacteria were
      identified to colonize infant gut, including bacteria from Bifidobacterium,
      Staphylococcus, Lactobacillus, and Escherichia/Shigella. Here, to identify the
      breast milk bacteria capable of colonizing gut without the interference of
      bacteria of origins other than the milk or the necessity to analyze infant feces,
      normal chow-fed germ-free mice were orally inoculated with the breast milk
      collected from a mother 2 days after vaginal delivery. According to 16S rRNA gene
      based denaturant gradient gel electrophoresis and Illumina sequencing, bacteria
      at >1% abundance in the milk inoculum were only Streptococcus (56.0%) and
      Staphylococcus (37.4%), but in the feces of recipient mice were Streptococcus
      (80.3 +/- 2.3%), Corynebacterium (10.0 +/- 2.6 %), Staphylococcus (7.6 +/- 1.6%),
      and Propionibacterium (2.1 +/- 0.5%) that were previously shown as dominant
      bacterial genera in the meconium of C-section-delivered human babies; the
      abundance of anaerobic gut-associated bacteria, Faecalibacterium, Prevotella,
      Roseburia, Ruminococcus, and Bacteroides, was 0.01-1% in the milk inoculum and
      0.003-0.01% in mouse feces; the abundance of Bifidobacterium spp. was below the
      detection limit of Illumina sequencing in the milk but at 0.003-0.01% in mouse
      feces. The human breast milk microbiota-associated mouse model may be used to
      identify additional breast milk bacteria that potentially colonize infant gut.

PMID- 28744260
TI  - PipY, a Member of the Conserved COG0325 Family of PLP-Binding Proteins, Expands
      the Cyanobacterial Nitrogen Regulatory Network.
AB  - Synechococcus elongatus PCC 7942 is a paradigmatic model organism for nitrogen
      regulation in cyanobacteria. Expression of genes involved in nitrogen
      assimilation is positively regulated by the 2-oxoglutarate receptor and global
      transcriptional regulator NtcA. Maximal activation requires the subsequent
      binding of the co-activator PipX. PII, a protein found in all three domains of
      life as an integrator of signals of the nitrogen and carbon balance, binds to
      PipX to counteract NtcA activity at low 2-oxoglutarate levels. PII-PipX complexes
      can also bind to the transcriptional regulator PlmA, whose regulon remains
      unknown. Here we expand the nitrogen regulatory network to PipY, encoded by the
      bicistronic operon pipXY in S. elongatus. Work with PipY, the cyanobacterial
      member of the widespread family of COG0325 proteins, confirms the conserved roles
      in vitamin B6 and amino/keto acid homeostasis and reveals new PLP-related
      phenotypes, including sensitivity to antibiotics targeting essential PLP
      holoenzymes or synthetic lethality with cysK. In addition, the related phenotypes
      of pipY and pipX mutants are consistent with genetic interactions in the contexts
      of survival to PLP-targeting antibiotics and transcriptional regulation. We also
      showed that PipY overexpression increased the length of S. elongatus cells. Taken
      together, our results support a universal regulatory role for COG0325 proteins,
      paving the way to a better understanding of these proteins and of their
      connections with other biological processes.

PMID- 28744261
TI  - Antifungal Potential of Copper(II), Manganese(II) and Silver(I) 1,10
      Phenanthroline Chelates Against Multidrug-Resistant Fungal Species Forming the
      Candida haemulonii Complex: Impact on the Planktonic and Biofilm Lifestyles.
AB  - Candida haemulonii, Candida haemulonii var. vulnera and Candida duobushaemulonii,
      which form the C. haemulonii complex, are emerging etiologic agents of fungal
      infections known to be resistant to the most commonly used antifungals. The well
      established anti-Candida potential of metal complexes containing 1,10
      phenanthroline (phen) ligands encouraged us to evaluate different copper(II),
      manganese(II), and silver(I) phen chelates for their ability to inhibit
      planktonic growth and biofilm of C. haemulonii species complex. Two novel
      coordination complexes, {[Cu(3,6,9-tdda)(phen)2].3H2O.EtOH}n and [Ag2(3,6,9
      tdda)(phen)4].EtOH (3,6,9-tddaH2 = 3,6,9-trioxaundecanedioic acid), were
      synthesized in a similar fashion to the other, previously documented, sixteen
      copper(II), manganese(II), and silver(I) chelates employed herein. Three isolates
      of each C. haemulonii species complex were used and the effect of the metal
      chelates on viability was determined utilizing the CLSI standard protocol and on
      biofilm-growing cells using the XTT assay. Cytotoxicity of the chelates was
      evaluated by the MTT assay, employing lung epithelial cells. The majority of the
      metal chelates were capable of interfering with the viability of planktonic
      growing cells of all the fungal isolates. The silver complexes were the most
      effective drugs (overall geometric mean of the minimum inhibitory concentration
      (GM-MIC) ranged from 0.26 to 2.16 MUM), followed by the manganese (overall GM-MIC
      ranged from 0.87 to 10.71 MUM) and copper (overall GM-MIC ranged from 3.37 to >72
      MUM) chelates. The manganese chelates (CC50 values ranged from 234.51 to >512
      MUM) were the least toxic to the mammalian cells, followed by the silver (CC50
      values ranged from 2.07 to 13.63 MUM) and copper (CC50 values ranged from 0.53 to
      3.86 MUM) compounds. When tested against mature biofilms, the chelates were less
      active, with MICs ranging from 2- to 33-fold higher levels when compared to the
      planktonic MIC counterparts. Importantly, manganese(II), copper(II), and
      silver(I) phen chelates are relatively cheap and easy to synthesize and they
      offer significant antifungal chemotherapeutic potential for the treatment of
      highly resistant pathogens.

PMID- 28744262
TI  - Distinct Aeromonas Populations in Water Column and Associated with Copepods from
      Estuarine Environment (Seine, France).
AB  - Aeromonas spp. are ubiquitous bacteria primarily recovered from aquatic
      ecosystems. They are found in fresh water as well as estuarine and marine waters,
      and in association with numerous autochthonous aquatic organisms in these
      environments. However, aeromonads are also etiologic agents of fish diseases and
      are now recognized as emerging pathogens in humans. The estuary is therefore a
      key environment, harboring autochthonous aeromonads, and aeromonads originating
      from humans and animals, mainly released by treated WWTP effluent or watershed
      run-off via tributaries. The present study compares the abundance and the
      diversity of Aeromonas populations. Over 2 years of monitoring (eight campaigns
      from February 2013 to November 2015), the occurrence of Aeromonas was
      investigated within the water column (water and fluid mud) and in association
      with copepods. Moreover, the diversity of Aeromonas populations was ascertained
      by analyzing gyrB and radA sequences, and the antibiotic-resistance phenotypes
      were determined using the disk diffusion method. This study shows, for the first
      time, the presence of Aeromonas spp. in water (1.1 * 102 to 1.2 +/- 0.3 * 103
      CFU.100 mL-1), fluid mud (2.6 +/- 2.6 * 102 to 9.8 +/- 0.9 * 103 CFU.g-1) and in
      association with living copepods (1.9 +/- 0.7 * 102 to >1.1 * 104 CFU.g-1) in the
      Seine estuary. Moreover, the diversity study, conducted on 36 strains isolated
      from the water column and 47 strains isolated from copepods, indicates distinct
      populations within these two compartments. Strains distributed in five clusters
      corresponding to A. bestiarum (n = 6; 5.45%), A. encheleia (n = 1; 0.91%), A.
      media (n = 22; 20.0%), A. rivipollensis (n = 34; 30.91%) and A. salmonicida (n =
      47; 42.73%). A. salmonicida is the most abundant species associated with
      Eurytemora affinis (n = 35; 74.47%). In contrast, A. salmonicida accounts for
      only 30.56% (n = 11) of isolates in the water column. This study shows the
      coexistence of distinct populations of Aeromonas in the oligohaline area of an
      anthropized estuary. Moreover, A. media, a putative human pathogen, present in
      the water column and abundant in the WWTP samples, was not detected in
      association with living copepods.

PMID- 28744264
TI  - Long-Term Rock Phosphate Fertilization Impacts the Microbial Communities of Maize
      Rhizosphere.
AB  - Phosphate fertilization is a common practice in agriculture worldwide, and
      several commercial products are widely used. Triple superphosphate (TSP) is an
      excellent soluble phosphorus (P) source. However, its high cost of production
      makes the long-term use of crude rock phosphate (RP) a more attractive
      alternative in developing countries, albeit its influence on plant-associated
      microbiota remains unclear. Here, we compared long-term effects of TSP and RP
      fertilization on the structure of maize rhizosphere microbial community using
      next generation sequencing. Proteobacteria were dominant in all conditions,
      whereas Oxalobacteraceae (mainly Massilia and Herbaspirillum) was enriched in the
      RP-amended soil. Klebsiella was the second most abundant taxon in the RP-treated
      soil. Burkholderia sp. and Bacillus sp. were enriched in the RP-amended soil when
      compared to the TSP-treated soil. Regarding fungi, Glomeromycota showed highest
      abundance in RP-amended soils, and the main genera were Scutellospora and
      Racocetra. These taxa are already described as important for P
      solubilization/acquisition in RP-fertilized soil. Maize grown on TSP and RP
      treated soil presented similar productivity, and a positive correlation was
      detected for P content and the microbial community of the soils. The results
      suggest changes of the microbial community composition associated to the type of
      phosphate fertilization. Whilst it is not possible to establish causality
      relations, our data highlights a few candidate taxa that could be involved in RP
      solubilization and plant growth promotion. Moreover, this can represent a shorter
      path for further studies aiming the isolation and validation of the taxa
      described here concerning P release on the soil plant system and their use as
      bioinoculants.

PMID- 28744263
TI  - Recombinant Invasive Lactococcus lactis Carrying a DNA Vaccine Coding the Ag85A
      Antigen Increases INF-gamma, IL-6, and TNF-alpha Cytokines after Intranasal
      Immunization.
AB  - Tuberculosis (TB) remains a major threat throughout the world and in 2015 it
      caused the death of 1.4 million people. The Bacillus Calmette-Guerin is the only
      existing vaccine against this ancient disease; however, it does not provide
      complete protection in adults. New vaccines against TB are eminently a global
      priority. The use of bacteria as vehicles for delivery of vaccine plasmids is a
      promising vaccination strategy. In this study, we evaluated the use of, an
      engineered invasive Lactococcus lactis (expressing Fibronectin-Binding Protein A
      from Staphylococcus aureus) for the delivery of DNA plasmid to host cells,
      especially to the mucosal site as a new DNA vaccine against tuberculosis. One of
      the major antigens documented that offers protective responses against
      Mycobacterium tuberculosis is the Ag85A. L. lactis FnBPA+ (pValac:Ag85A) which
      was obtained and used for intranasal immunization of C57BL/6 mice and the immune
      response profile was evaluated. In this study we observed that this strain was
      able to produce significant increases in the amount of pro-inflammatory cytokines
      (IFN-gamma, TNF-alpha, and IL-6) in the stimulated spleen cell supernatants,
      showing a systemic T helper 1 (Th1) cell response. Antibody production (IgG and
      sIgA anti-Ag85A) was also significantly increased in bronchoalveolar lavage, as
      well as in the serum of mice. In summary, these findings open new perspectives in
      the area of mucosal DNA vaccine, against specific pathogens using a Lactic Acid
      Bacteria such as L. lactis.

PMID- 28744265
TI  - Bacterial Community Dynamics and Biocement Formation during Stimulation and
      Augmentation: Implications for Soil Consolidation.
AB  - Microbially-induced CaCO3 precipitation (MICP) is a naturally occurring process
      wherein durable carbonates are formed as a result of microbial metabolic
      activities. In recent years, MICP technology has been widely harnessed for
      applications in civil engineering wherein synthesis of calcium carbonate crystals
      occurs at ambient temperature paving way for low energy biocement. MICP using
      pure urease (UA) and carbonic anhydrase (CA) producing bacteria has been
      promising in laboratory conditions. In the current study we enriched ureolytic
      and carbonic anhydrase communities in calcareous soil under biostimulation and
      bioaugmentation conditions and investigated the effect of microbial dynamics on
      carbonate precipitation, calcium carbonate polymorph selection and consolidation
      of biological sand column under nutrient limited and rich conditions. All
      treatments for stimulation and augmentation led to significant changes in the
      composition of indigenous bacterial population. Biostimulation as well as
      augmentation through the UA route was found to be faster and more effective
      compared to the CA route in terms of extracellular enzyme production and
      carbonate precipitation. Synergistic role of augmented cultures along with
      indigenous communities was recorded via both the routes of UA and CA as more
      effective calcification was seen in case of augmentation compared to stimulation.
      The survival of supplemented isolates in presence of indigenous bacterial
      communities was confirmed through sequencing of total diversity and it was seen
      that both UA and CA isolate had the potential to survive along with native
      communities under high nutrient conditions. Nutrient conditions played
      significant role in determining calcium carbonate polymorph fate as calcitic
      crystals dominated under high carbon supplementation. Finally, the consolidation
      of sand columns via stimulation and augmentation was successfully achieved
      through both UA and CA route under high nutrient conditions but higher
      consolidation in short time period was noticed in UA route. The study reports
      that based upon the organic carbon content in native soils, stimulation can be
      favored at sites with high organic carbon content while augmentation with
      repeated injections of nutrients can be applied on poor nutrient soils via
      different enrichment routes of microbial metabolism.

PMID- 28744266
TI  - Nutrient and Rainfall Additions Shift Phylogenetically Estimated Traits of Soil
      Microbial Communities.
AB  - Microbial traits related to ecological responses and functions could provide a
      common currency facilitating synthesis and prediction; however, such traits are
      difficult to measure directly for all taxa in environmental samples. Past efforts
      to estimate trait values based on phylogenetic relationships have not always
      distinguished between traits with high and low phylogenetic conservatism,
      limiting reliability, especially in poorly known environments, such as soil.
      Using updated reference trees and phylogenetic relationships, we estimated two
      phylogenetically conserved traits hypothesized to be ecologically important from
      DNA sequences of the 16S rRNA gene from soil bacterial and archaeal communities.
      We sampled these communities from an environmental change experiment in
      California grassland applying factorial addition of late-season precipitation and
      soil nutrients to multiple soil types for 3 years prior to sampling. Estimated
      traits were rRNA gene copy number, which contributes to how rapidly a microbe can
      respond to an increase in resources and may be related to its maximum growth
      rate, and genome size, which suggests the breadth of environmental and substrate
      conditions in which a microbe can thrive. Nutrient addition increased community
      weighted mean estimated rRNA gene copy number and marginally increased estimated
      genome size, whereas precipitation addition decreased these community means for
      both estimated traits. The effects of both treatments on both traits were
      associated with soil properties, such as ammonium, available phosphorus, and pH.
      Estimated trait responses within several phyla were opposite to the community
      mean response, indicating that microbial responses, although largely consistent
      among soil types, were not uniform across the tree of life. Our results show that
      phylogenetic estimation of microbial traits can provide insight into how
      microbial ecological strategies interact with environmental changes. The method
      could easily be applied to any of the thousands of existing 16S rRNA sequence
      data sets and offers potential to improve our understanding of how microbial
      communities mediate ecosystem function responses to global changes.

PMID- 28744267
TI  - The Staphylococcus aureus alpha-Acetolactate Synthase ALS Confers Resistance to
      Nitrosative Stress.
AB  - Staphylococcus aureus is a worldwide pathogen that colonizes the human nasal
      cavity and is a major cause of respiratory and cutaneous infections. In the nasal
      cavity, S. aureus thrives with high concentrations of nitric oxide (NO) produced
      by the innate immune effectors and has available for growth slow-metabolizing
      free hexoses, such as galactose. Here, we have used deep sequencing
      transcriptomic analysis (RNA-Seq) and 1H-NMR to uncover how S. aureus grown on
      galactose, a major carbon source present in the nasopharynx, survives the
      deleterious action of NO. We observed that, like on glucose, S. aureus withstands
      high concentrations of NO when using galactose. Data indicate that this
      resistance is, most likely, achieved through a distinct metabolism that relies on
      the increased production of amino acids, such as glutamate, threonine, and
      branched-chain amino acids (BCAAs). Moreover, we found that under NO stress the
      S. aureus alpha-acetolactate synthase (ALS) enzyme, which converts pyruvate into
      alpha-acetolactate, plays an important role. ALS is proposed to prevent
      intracellular acidification, to promote the production of BCAAs and the
      activation of the TCA cycle. Additionally, ALS is shown to contribute to the
      successful infection of murine macrophages. Furthermore, ALS contributes to the
      resistance of S. aureus to beta-lactam antibiotics such as methicillin and
      oxacillin.

PMID- 28744268
TI  - Intestinal Anti-inflammatory Effects of Outer Membrane Vesicles from Escherichia
      coli Nissle 1917 in DSS-Experimental Colitis in Mice.
AB  - Escherichia coli Nissle 1917 (EcN) is a probiotic strain with proven efficacy in
      inducing and maintaining remission of ulcerative colitis. However, the microbial
      factors that mediate these beneficial effects are not fully known. Gram-negative
      bacteria release outer membrane vesicles (OMVs) as a direct pathway for
      delivering selected bacterial proteins and active compounds to the host. In fact,
      vesicles released by gut microbiota are emerging as key players in signaling
      processes in the intestinal mucosa. In the present study, the dextran sodium
      sulfate (DSS)-induced colitis mouse model was used to investigate the potential
      of EcN OMVs to ameliorate mucosal injury and inflammation in the gut. The
      experimental protocol involved pre-treatment with OMVs for 10 days before DSS
      intake, and a 5-day recovery period. Oral administration of purified EcN OMVs (5
      MUg/day) significantly reduced DSS-induced weight loss and ameliorated clinical
      symptoms and histological scores. OMVs treatment counteracted altered expression
      of cytokines and markers of intestinal barrier function. This study shows for the
      first time that EcN OMVs can mediate the anti-inflammatory and barrier protection
      effects previously reported for this probiotic in experimental colitis.
      Remarkably, translation of probiotics to human healthcare requires knowledge of
      the molecular mechanisms involved in probiotic-host interactions. Thus, OMVs, as
      a non-replicative bacterial form, could be explored as a new probiotic-derived
      therapeutic approach, with even lower risk of adverse events than probiotic
      administration.

PMID- 28744269
TI  - Comparative Genomics of Methanopyrus sp. SNP6 and KOL6 Revealing Genomic Regions
      of Plasticity Implicated in Extremely Thermophilic Profiles.
AB  - Methanopyrus spp. are usually isolated from harsh niches, such as high osmotic
      pressure and extreme temperature. However, the molecular mechanisms for their
      environmental adaption are poorly understood. Archaeal species is commonly
      considered as primitive organism. The evolutional placement of archaea is a
      fundamental and intriguing scientific question. We sequenced the genomes of
      Methanopyrus strains SNP6 and KOL6 isolated from the Atlantic and Iceland,
      respectively. Comparative genomic analysis revealed genetic diversity and
      instability implicated in niche adaption, including a number of transporter- and
      integrase/transposase-related genes. Pan-genome analysis also defined the gene
      pool of Methanopyrus spp., in addition of ~120-Kb genomic region of plasticity
      impacting cognate genomic architecture. We believe that Methanopyrus genomics
      could facilitate efficient investigation/recognition of archaeal phylogenetic
      diverse patterns, as well as improve understanding of biological roles and
      significance of these versatile microbes.

PMID- 28744270
TI  - Occurrence of the mcr-1 Colistin Resistance Gene and other Clinically Relevant
      Antibiotic Resistance Genes in Microbial Populations at Different Municipal
      Wastewater Treatment Plants in Germany.
AB  - Seven wastewater treatment plants (WWTPs) with different population equivalents
      and catchment areas were screened for the prevalence of the colistin resistance
      gene mcr-1 mediating resistance against last resort antibiotic polymyxin E. The
      abundance of the plasmid-associated mcr-1 gene in total microbial populations
      during water treatment processes was quantitatively analyzed by qPCR analyses.
      The presence of the colistin resistance gene was documented for all of the
      influent wastewater samples of the seven WWTPs. In some cases the mcr-1
      resistance gene was also detected in effluent samples of the WWTPs after
      conventional treatment reaching the aquatic environment. In addition to the
      occurrence of mcr-1 gene, CTX-M-32, blaTEM, CTX-M, tetM, CMY-2, and ermB genes
      coding for clinically relevant antibiotic resistances were quantified in higher
      abundances in all WWTPs effluents. In parallel, the abundances of Acinetobacter
      baumannii, Klebsiella pneumoniae, and Escherichia coli were quantified via qPCR
      using specific taxonomic gene markers which were detected in all influent and
      effluent wastewaters in significant densities. Hence, opportunistic pathogens and
      clinically relevant antibiotic resistance genes in wastewaters of the analyzed
      WWTPs bear a risk of dissemination to the aquatic environment. Since many of the
      antibiotic resistance gene are associated with mobile genetic elements horizontal
      gene transfer during wastewater treatment can't be excluded.

PMID- 28744271
TI  - Dual Induction of New Microbial Secondary Metabolites by Fungal Bacterial Co
      cultivation.
AB  - The frequent re-isolation of known compounds is one of the major challenges in
      drug discovery. Many biosynthetic genes are not expressed under standard culture
      conditions, thus limiting the chemical diversity of microbial compounds that can
      be obtained through fermentation. On the other hand, the competition during co
      cultivation of two or more different microorganisms in most cases leads to an
      enhanced production of constitutively present compounds or an accumulation of
      cryptic compounds that are not detected in axenic cultures of the producing
      strain under different fermentation conditions. Herein, we report the dual
      induction of newly detected bacterial and fungal metabolites by the co
      cultivation of the marine-derived fungal isolate Aspergillus fumigatus MR2012 and
      two hyper-arid desert bacterial isolates Streptomyces leeuwenhoekii strain C34
      and strain C58. Co-cultivation of the fungal isolate MR2012 with the bacterial
      strain C34 led to the production of luteoride D, a new luteoride derivative and
      pseurotin G, a new pseurotin derivative in addition to the production of terezine
      D and 11-O-methylpseurotin A which were not traced before from this fungal strain
      under different fermentation conditions. In addition to the previously detected
      metabolites in strain C34, the lasso peptide chaxapeptin was isolated under co
      culture conditions. The gene cluster for the latter compound had been identified
      through genome scanning, but it had never been detected before in the axenic
      culture of strain C34. Furthermore, when the fungus MR2012 was co-cultivated with
      the bacterial strain C58, the main producer of chaxapeptin, the titre of this
      metabolite was doubled, while additionally the bacterial metabolite pentalenic
      acid was detected and isolated for the first time from this strain, whereas the
      major fungal metabolites that were produced under axenic culture were suppressed.
      Finally, fermentation of the MR2012 by itself led to the isolation of the new
      diketopiperazine metabolite named brevianamide X.

PMID- 28744272
TI  - Biosurfactant as an Enhancer of Geologic Carbon Storage: Microbial Modification
      of Interfacial Tension and Contact Angle in Carbon dioxide/Water/Quartz Systems.
AB  - Injecting and storing of carbon dioxide (CO2) in deep geologic formations is
      considered as one of the promising approaches for geologic carbon storage.
      Microbial wettability alteration of injected CO2 is expected to occur naturally
      by microorganisms indigenous to the geologic formation or microorganisms
      intentionally introduced to increase CO2 storage capacity in the target
      reservoirs. The question as to the extent of microbial CO2 wettability alteration
      under reservoir conditions still warrants further investigation. This study
      investigated the effect of a lipopeptide biosurfactant-surfactin, on interfacial
      tension (IFT) reduction and contact angle alteration in CO2/water/quartz systems
      under a laboratory setup simulating in situ reservoir conditions. The temporal
      shifts in the IFT and the contact angle among CO2, brine, and quartz were
      monitored for different CO2 phases (3 MPa, 30 degrees C for gaseous CO2; 10 MPa,
      28 degrees C for liquid CO2; 10 MPa, 37 degrees C for supercritical CO2) upon
      cultivation of Bacillus subtilis strain ATCC6633 with induced surfactin secretion
      activity. Due to the secreted surfactin, the IFT between CO2 and brine decreased:
      from 49.5 to 30 mN/m, by ~39% for gaseous CO2; from 28.5 to 13 mN/m, by 54% for
      liquid CO2; and from 32.5 to 18.5 mN/m, by ~43% for supercritical CO2,
      respectively. The contact angle of a CO2 droplet on a quartz disk in brine
      increased: from 20.5 degrees  to 23.2 degrees , by 1.16 times for gaseous CO2;
      from 18.4 degrees  to 61.8 degrees , by 3.36 times for liquid CO2; and from 35.5
      degrees  to 47.7 degrees , by 1.34 times for supercritical CO2, respectively.
      With the microbially altered CO2 wettability, improvement in sweep efficiency of
      injected and displaced CO2 was evaluated using 2-D pore network model
      simulations; again the increment in sweep efficiency was the greatest in liquid
      CO2 phase due to the largest reduction in capillary factor. This result provides
      novel insights as to the role of naturally occurring biosurfactants in CO2
      storage and suggests that biostimulation of biosurfactant production may be a
      feasible technique for enhancement of CO2 storage capacity.

PMID- 28744273
TI  - Oral Probiotics Alter Healthy Feline Respiratory Microbiota.
AB  - Probiotics have been advocated as a novel therapeutic approach to respiratory
      disease, but knowledge of how oral administration of probiotics influences the
      respiratory microbiota is needed. Using 16S rRNA amplicon sequencing of bacterial
      DNA our objective was to determine whether oral probiotics changed the
      composition of the upper and lower airway, rectal, and blood microbiota. We
      hypothesized that oral probiotics would modulate the respiratory microbiota in
      healthy cats, demonstrated by the detection and/or increased relative abundance
      of the probiotic bacterial species and altered composition of the microbial
      population in the respiratory tract. Six healthy young research cats had
      oropharyngeal (OP), bronchoalveolar lavage fluid (BALF), rectal, and blood
      samples collected at baseline and 4 weeks after receiving oral probiotics. 16S
      rRNA gene amplicon libraries were sequenced, and coverage, richness, and relative
      abundance of representative operational taxonomic units (OTUs) were determined.
      Hierarchical and principal component analyses (PCA) demonstrated relatedness of
      samples. Mean microbial richness significantly increased only in the upper and
      lower airways. The number of probiotic OTUs (out of 5 total) that significantly
      increased in relative abundance vs. baseline was 5 in OP, 3 in BAL and 2 in
      feces. Using hierarchical clustering, BALF and blood samples grouped together
      after probiotic administration, and PERMANOVA supported that these two sites
      underwent significant changes in microbial composition. PERMANOVA revealed that
      OP and rectal samples had microbial population compositions that did not
      significantly change. These findings were visualized via PCA, which revealed
      distinct microbiomes in each site; samples clustered more tightly at baseline and
      had more variation after probiotic administration. This is the first study
      describing the effect of oral probiotics on the respiratory microbiota via
      detection of probiotic species in the airways. Finding bacterial species present
      in the oral probiotics in the upper and lower airways provides pilot data
      suggesting that oral probiotics could serve as a tool to target dysbiosis
      occurring in inflammatory airway diseases such as feline asthma, a disease in
      which cats serve as an important comparative and translational model for humans.

PMID- 28744274
TI  - Tobramycin and Amikacin Delay Adhesion and Microcolony Formation in Pseudomonas
      aeruginosa Cystic Fibrosis Isolates.
AB  - Cystic fibrosis (CF) patients are predisposed to chronic colonization of the
      major airways by Pseudomonas aeruginosa biofilms. Pulmonary infections, involving
      sessile bacteria, are the main cause of morbidity and mortality. As the
      eradication of antibiotic-resistant biofilms remains impossible, one key
      objective for the treatment of lung infections is to delay the switch of P.
      aeruginosa to a sessile phenotype. Few tools are currently available in hospital
      laboratories to evaluate the susceptibility of adherent microorganisms to
      antimicrobials. In this study, we used the Biofilm Ring Test(r), for the
      achievement of Antibiofilmograms(r) on CF clinical isolates. In comparison to
      standard antibiograms, these procedures allow the investigation of antibiotic
      effects on the biofilm formation by bacteria. To confirm the inter-assay
      reproducibility, conventional Crystal Violet assays were performed. To mimic the
      pathologic reality of CF, we also used a model allowing the biofilm growth on CF
      derived cells. Results obtained from these three different assays showed that
      amikacin and tobramycin, the two favored aminoglycosides in CF therapies, were
      able to prevent the early adhesion of P. aeruginosa isolates. This promising
      inhibitory effect of antimicrobials confirm that biofilm setting up is governed
      by adaptive responses and depends on environmental conditions, as opposite
      processes of biofilm induction by aminoglycosides were previously described in
      literature. Finally, Antibiofilmograms(r), whose given results are in concordance
      with other in vitro antibiotic susceptibility testing, appear to be useful for
      the optimisation of CF therapies by the selection of antimicrobials able to delay
      chronic infection establishment.

PMID- 28744275
TI  - Staphylococcus aureus Quorum Regulator SarA Targeted Compound, 2
      [(Methylamino)methyl]phenol Inhibits Biofilm and Down-Regulates Virulence Genes.
AB  - Staphylococcus aureus is a widely acknowledged Gram-positive pathogen for forming
      biofilm and virulence gene expressions by quorum sensing (QS), a cell to cell
      communication process. The quorum regulator SarA of S. aureus up-regulates the
      expression of many virulence factors including biofilm formation to mediate
      pathogenesis and evasion of the host immune system in the late phases of growth.
      Thus, inhibiting the production or blocking SarA protein might influence the down
      regulation of biofilm and virulence factors. In this context, here we have
      synthesized 2-[(Methylamino)methyl]phenol, which was specifically targeted toward
      the quorum regulator SarA through in silico approach in our previous study. The
      molecule has been evaluated in vitro to validate its antibiofilm activity against
      clinical S. aureus strains. In addition, antivirulence properties of the
      inhibitor were confirmed with the observation of a significant reduction in the
      expression of representative virulence genes like fnbA, hla and hld that are
      governed under S. aureus QS. Interestingly, the SarA targeted inhibitor showed
      negligible antimicrobial activity and markedly reduced the minimum inhibitory
      concentration of conventional antibiotics when used in combination making it a
      more attractive lead for further clinical tests.

PMID- 28744276
TI  - Differential Antifungal Activity of Human and Cryptococcal Melanins with
      Structural Discrepancies.
AB  - Melanin is a pigment found in all biological kingdoms, and plays a key role in
      protection against ultraviolet radiation, oxidizing agents, and ionizing
      radiation damage. Melanin exerts an antimicrobial activity against bacteria,
      fungi, and parasites. We demonstrated an antifungal activity of synthetic and
      human melanin against Candida sp. The members of the Cryptococcus neoformans and
      C. gattii species complexes are capsulated yeasts, which cause cryptococcosis.
      For both species melanin is an important virulence factor. To evaluate if
      cryptococcal and human melanins have antifungal activity against Cryptococcus
      species they both were assayed for their antifungal properties and physico
      chemical characters. Melanin extracts from human hair and different strains of C.
      neoformans (n = 4) and C. gattii (n = 4) were investigated. The following minimum
      inhibitory concentrations were found for different melanins against C. neoformans
      and C. gattii were (average/range): 13.7/(7.8-15.6) and 19.5/(15.6-31.2) MUg/mL,
      respectively, for human melanin; 273.4/(125->500) and 367.2/(125.5->500) MUg/mL
      for C. neoformans melanin and 125/(62.5-250) and 156.2/(62-250) MUg/mL for C.
      gattii melanin. Using Scanning Electron Microscopy we observed that human melanin
      showed a compact conformation and cryptococcal melanins exposed an amorphous
      conformation. Infrared spectroscopy (FTIR) showed some differences in the signals
      related to C-C bonds of the aromatic ring of the melanin monomers. High
      Performance Liquid Chromatography established differences in the chromatograms of
      fungal melanins extracts in comparison with human and synthetic melanin,
      particularly in the retention time of the main compound of fungal melanin
      extracts and also in the presence of minor unknown compounds. On the other hand,
      MALDI-TOF-MS analysis showed slight differences in the spectra, specifically the
      presence of a minor intensity ion in synthetic and human melanin, as well as in
      some fungal melanin extracts. We conclude that human melanin is more active than
      the two fungal melanins against Cryptococcus. Although some physico-chemical
      differences were found, they do not explain the differences in the antifungal
      activity against Cryptococcus of human and cryptococcal melanins. More detailed
      studies on the structure should be considered to associate structure and
      antifungal activity.

PMID- 28744277
TI  - Anti-adhesion and Anti-biofilm Potential of Organosilane Nanoparticles against
      Foodborne Pathogens.
AB  - Nowadays, modification of surfaces by nanoparticulate coatings is a simple
      process that may have applications in reducing the prevalence of bacterial cells
      both on medical devices and food processing surfaces. To this direction, biofilm
      biological cycle of Salmonella Typhimurium, Listeria monocytogenes, Escherichia
      coli O157:H7, Staphylococcus aureus, and Yersinia enterocolitica on stainless
      steel and glass surfaces, with or without nanocoating was monitored. To achieve
      this, four different commercial nanoparticle compounds (two for each surface)
      based on organo-functionalized silanes were selected. In total 10 strains of
      above species (two for each species) were selected to form biofilms on modified
      or not, stainless steel or glass surfaces, incubated at 37 degrees C for 72 h.
      Biofilm population was enumerated by bead vortexing-plate counting method at four
      time intervals (3, 24, 48, and 72 h). Organosilane based products seemed to
      affect bacterial attachment on the inert surfaces and/or subsequent biofilm
      formation, but it was highly dependent on the species and material of surfaces
      involved. Specifically, reduced bacterial adhesion (at 3 h) of Salmonella and E.
      coli was observed (P < 0.05) in nanocoating glass surfaces in comparison with the
      control ones. Moreover, fewer Salmonella and Yersinia biofilm cells were
      enumerated on stainless steel coupons coated with organosilanes, than on non
      coated surfaces at 24 h (P < 0.05). This study gives an insight to the efficacy
      of organosilanes based coatings against biofilm formation of foodborne pathogens,
      however, further studies are needed to better understand the impact of surface
      modification and the underlying mechanisms which are involved in this phenomenon.

PMID- 28744278
TI  - Fungal Communities in Rhizosphere Soil under Conservation Tillage Shift in
      Response to Plant Growth.
AB  - Conservation tillage is an extensively used agricultural practice in northern
      China that alters soil texture and nutrient conditions, causing changes in the
      soil microbial community. However, how conservation tillage affects rhizosphere
      and bulk soil fungal communities during plant growth remains unclear. The present
      study investigated the effect of long-term (6 years) conservation (chisel plow,
      zero) and conventional (plow) tillage during wheat growth on the rhizosphere
      fungal community, using high-throughput sequencing of the internal transcribed
      spacer (ITS) gene and quantitative PCR. During tillering, fungal alpha diversity
      in both rhizosphere and bulk soil were significantly higher under zero tillage
      compared to other methods. Although tillage had no significant effect during the
      flowering stage, fungal alpha diversity at this stage was significantly different
      between rhizosphere and bulk soils, with bulk soil presenting the highest
      diversity. This was also reflected in the phylogenetic structure of the
      communities, as rhizosphere soil communities underwent a greater shift from
      tillering to flowering compared to bulk soil communities. In general, less
      variation in community structure was observed under zero tillage compared to plow
      and chisel plow treatments. Changes in the relative abundance of the fungal
      orders Capnodiales, Pleosporales, and Xylariales contributed the highest to the
      dissimilarities observed. Structural equation models revealed that the soil
      fungal communities under the three tillage regimes were likely influenced by the
      changes in soil properties associated with plant growth. This study suggested
      that: (1) differences in nutrient resources between rhizosphere and bulk soils
      can select for different types of fungi thereby increasing community variation
      during plant growth; (2) tillage can alter fungal communities' variability, with
      zero tillage promoting more stable communities. This work suggests that long-term
      changes in tillage regimes may result in unique soil fungal ecology, which might
      influence other aspects of soil functioning (e.g., decomposition).

PMID- 28744279
TI  - Role of Inactive and Active Trypanosoma cruzi Trans-sialidases on T Cell Homing
      and Secretion of Inflammatory Cytokines.
AB  - Trans-sialidase from Trypanosoma cruzi (Tc-TS) belongs to a superfamily of
      proteins that may have enzymatic activity. While enzymatically active members (Tc
      aTS) are able to transfer sialic acid from the host cell sialyl-glycoconjugates
      onto the parasite or to other molecules on the host cell surface, the inactive
      members (Tc-iTS) are characterized by their lectinic properties. Over the last 10
      years, several papers demonstrated that, individually, Tc-aTS or Tc-iTS is able
      to modulate several biological events. Since the genes encoding Tc-iTS and Tc-aTS
      are present in the same copy number, and both proteins portray similar substrate
      specificities as well, it would be plausible to speculate that such molecules may
      compete for the same sialyl-glycan structures and govern numerous
      immunobiological phenomena. However, their combined effect has never been
      evaluated in the course of an acute infection. In this study, we investigated the
      ability of both proteins to modulate the production of inflammatory signals, as
      well as the homing of T cells to the cardiac tissue of infected mice, events that
      usually occur during the acute phase of T. cruzi infection. The results showed
      that the intravenous administration of Tc-iTS, but not Tc-aTS protected the
      cardiac tissue from injury caused by reduced traffic of inflammatory cells. In
      addition, the ability of Tc-aTS to modulate the production of inflammatory
      cytokines was attenuated and/or compromised when Tc-iTS was co-injected in the
      same proportions. These results suggest that although both proteins present
      structural similarities and compete for the same sialyl-glycan epitopes, they
      might present distinct immunomodulatory properties on T cells following T. cruzi
      infection.

PMID- 28744280
TI  - Amino Acid Substitution K470R in the Nucleoprotein Increases the Virulence of
      H5N1 Influenza A Virus in Mammals.
AB  - H5N1 is a highly pathogenic influenza A virus (IAV) and poses a major threat to
      the public health. The nucleoprotein (NP) has a multiple functions during the
      viral life cycle, however, the precise role of NP mutants in viral replication
      and pathogenicity is not completely understood. Here, we attempted to identify
      five residues in NP that may contribute to viral replication or pathogenicity. Of
      these, K227R, K229R, and K470R viruses were successfully rescued by reverse
      genetic, but the K91R and K198R viruses were not viable. A mini-genome assay
      demonstrated that the NP mutations K91R and K198R significantly decreased the
      polymerase activity. Moreover, these two mutations resulted in disrupted cellular
      localization in mammalian cells. Importantly, mutation at position 470 of NP
      significantly increased its virulence in vitro and in vivo. These findings
      demonstrated that the NP protein plays a major role in influenza virulence and
      pathogenicity, which adds to the knowledge of IAV virulence determinants and may
      benefit IAV surveillance.

PMID- 28744281
TI  - Age-Related Variations in Intestinal Microflora of Free-Range and Caged Hens.
AB  - Free range feeding pattern puts the chicken in a mixture of growth materials and
      enteric bacteria excreted by nature, while it is typically unique condition
      materials and enteric bacteria in commercial caged hens production. Thus, the
      gastrointestinal microflora in two feeding patterns could be various. However, it
      remains poorly understood how feeding patterns affect development and composition
      of layer hens' intestinal microflora. In this study, the effect of feeding
      patterns on the bacteria community in layer hens' gut was investigated using free
      range and caged feeding form. Samples of whole small intestines and cecal digesta
      were collected from young hens (8-weeks) and mature laying hens (30-weeks). Based
      on analysis using polymerase chain reaction-denaturing gradient gel
      electrophoresis and sequencing of bacterial 16S rDNA gene amplicons, the
      microflora of all intestinal contents were affected by both feeding patterns and
      age of hens. Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and
      Fusobacteria were the main components. Additionally, uncultured environmental
      samples were found too. There were large differences between young hens and adult
      laying hens, the latter had more Firmicutes and Bacteroidetes, and bacterial
      community is more abundant in 30-weeks laying hens of all six phyla than 8-weeks
      young hens of only two phyla. In addition, the differences were also observed
      between free range and caged hens. Free range hens had richer Actinobacteria,
      Bacteroidetes, and Proteobacteria. Most of strains found were detected more
      abundant in small intestines than in cecum. Also the selected Lactic acid
      bacteria from hens gut were applied in feed and they had beneficial effects on
      growth performance and jejunal villus growth of young broilers. This study
      suggested that feeding patterns have an importance effect on the microflora
      composition of hens, which may impact the host nutritional status and intestinal
      health.

PMID- 28744282
TI  - Antiviral Properties of the Natural Polyphenols Delphinidin and Epigallocatechin
      Gallate against the Flaviviruses West Nile Virus, Zika Virus, and Dengue Virus.
AB  - The Flavivirus genus contains important pathogens, such as West Nile virus (WNV),
      Zika virus (ZIKV), and Dengue virus (DENV), which are enveloped plus-strand RNA
      viruses transmitted by mosquitoes and constitute a worrisome threat to global
      human and animal health. Currently no licensed drugs against them are available,
      being, thus, still necessary the search for effective antiviral molecules. In
      this line, a novel antiviral approach (economical, simple to use, and
      environmental friendly) is the use of natural compounds. Consequently, we have
      tested the antiviral potential of different polyphenols present in plants and
      natural products, such as wine and tea, against WNV, ZIKV, and DENV. So that, we
      assayed the effect of a panel of structurally related polyphenols [delphinidin
      (D), cyanidin (Cy), catechin (C), epicatechin (EC), epigallocatechin (EGC), and
      epigallocatechin gallate (EGCG)] on WNV infection, and found that D and EGCG
      inhibited more effectively the virus production. Further analysis with both
      compounds indicated that they mainly affected the attachment and entry steps of
      the virus life cycle. Moreover, D and EGCG showed a direct effect on WNV
      particles exerting a virucidal effect. We showed a similar inhibition of viral
      production of these compounds on WNV variants that differed on acidic pH
      requirements for viral fusion, indicating that their antiviral activity against
      WNV is produced by a virucidal effect rather than by an inhibition of pH
      dependent viral fusion. Both polyphenols also reduced the infectivity of ZIKV and
      DENV. Therefore, D and EGCG impair the infectivity in cell culture of these three
      medically relevant flaviviruses.

PMID- 28744283
TI  - Corrigendum: Why Quorum Sensing Controls Private Goods.
AB  - [This corrects the article on p. 885 in vol. 8, PMID: 28579979.].

PMID- 28744284
TI  - Safety and Side Effects of Using Placenta-Derived Decidual Stromal Cells for
      Graft-versus-Host Disease and Hemorrhagic Cystitis.
AB  - Mesenchymal stromal cells (MSCs) are increasingly used in regenerate medicine.
      Placenta-derived decidual stromal cells (DSCs) are a novel therapy for acute
      graft-versus-host-disease (GVHD) and hemorrhagic cystitis (HC) after allogeneic
      hematopoietic stem cell transplantation (HSCT). DSCs are more immunosuppressive
      than MSCs. We assessed adverse events and safety using DSCs among 44 treated
      patients and 40 controls. The median dose of infused cells was 1.5 (range 0.9
      2.9) * 106 DSCs/kg. The patients were given 2 (1-5) doses, with a total of 82
      infusions. Monitoring ended 3 months after the last DSC infusion. Three patients
      had transient reactions during DSC infusion. Laboratory values, hemorrhages, and
      transfusions were similar in the two groups. The frequency of leukemic relapse
      (2/2, DSC/controls) and invasive fungal infections (6/6) were the same in the two
      groups. Causes of death were those seen in HSCT patients: infections (5/3),
      respiratory failure (1/1), circulatory failure (3/1), thromboembolism (1/0),
      multiorgan failure (0/1), and GVHD and others (2/7). One-year survival for the
      DSC patients with GVHD was 67%, which was significantly better than achieved
      previously at our center. One-year survival was 90% in the DSC-treated HC group.
      DSC infusions appear safe. Randomized studies are required to prove efficacy.

PMID- 28744285
TI  - Placental Growth Factor Contributes to Liver Inflammation, Angiogenesis, Fibrosis
      in Mice by Promoting Hepatic Macrophage Recruitment and Activation.
AB  - Placental growth factor (PlGF), a member of the vascular endothelial growth
      factor (VEGF) family, mediates wound healing and inflammatory responses, exerting
      an effect on liver fibrosis and angiogenesis; however, the precise mechanism
      remains unclear. The aims of this study are to identify the role of PlGF in liver
      inflammation and fibrosis induced by bile duct ligation (BDL) in mice and to
      reveal the underlying molecular mechanism. PlGF small interfering RNA (siRNA) or
      non-targeting control siRNA was injected by tail vein starting 2 days after BDL.
      Liver inflammation, fibrosis, angiogenesis, macrophage infiltration, and hepatic
      stellate cells (HSCs) activation were examined. Our results showed that PlGF was
      highly expressed in fibrotic livers and mainly distributed in activated HSCs and
      macrophages. Furthermore, PlGF silencing strongly reduced the severity of liver
      inflammation and fibrosis, and inhibited the activation of HSCs. Remarkably, PlGF
      silencing also attenuated BDL-induced hepatic angiogenesis, as evidenced by
      attenuated liver endothelial cell markers CD31 and von Willebrand factor
      immunostaining and genes or protein expression. Interestingly, these pathological
      ameliorations by PlGF silencing were due to a marked reduction in the numbers of
      intrahepatic F4/80+, CD68+, and Ly6C+ cell populations, which were reflected by a
      lower expression of these macrophage marker molecules in fibrotic livers. In
      addition, knockdown of PlGF by siRNA inhibited macrophages activation and
      substantially suppressed the expression of pro-inflammatory cytokines and
      chemokines in fibrotic livers. Mechanistically, evaluation of cultured RAW 264.7
      cells revealed that VEGF receptor 1 (VEGFR1) mainly involved in mediating the
      role of PlGF in macrophages recruitment and activation, since using VEGFR1
      neutralizing antibody blocking PlGF/VEGFR1 signaling axis significantly inhibited
      macrophages migration and inflammatory responses. Together, these findings
      indicate that PlGF plays an important role in liver inflammation, angiogenesis,
      and fibrosis by promoting hepatic macrophage recruitment and activation, and
      suggest that blockage of PlGF could be a promising novel therapy for chronic
      fibrotic liver diseases.

PMID- 28744286
TI  - A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of
      Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune
      Encephalomyelitis Model.
AB  - The absence of pathological hallmarks of progressive multiple sclerosis (MS) in
      commonly used rodent models of experimental autoimmune encephalomyelitis (EAE)
      hinders the development of adequate treatments for progressive disease. Work
      reviewed here shows that such hallmarks are present in the EAE model in marmoset
      monkeys (Callithrix jacchus). The minimal requirement for induction of
      progressive MS pathology is immunization with a synthetic peptide representing
      residues 34-56 from human myelin oligodendrocyte glycoprotein (MOG) formulated
      with a mineral oil [incomplete Freund's adjuvant (IFA)]. Pathological aspects
      include demyelination of cortical gray matter with microglia activation,
      oxidative stress, and redistribution of iron. When the peptide is formulated in
      complete Freund's adjuvant, which contains mycobacteria that relay strong
      activation signals to myeloid cells, oxidative damage pathways are strongly
      boosted leading to more intensive pathology. The proven absence of immune
      potentiating danger signals in the MOG34-56/IFA formulation implies that a narrow
      population of antigen-experienced T cells present in the monkey's immune
      repertoire is activated. This novel pathway involves the interplay of
      lymphocryptovirus-infected B cells with MHC class Ib/Caja-E restricted CD8+ CD56+
      cytotoxic T lymphocytes.

PMID- 28744287
TI  - CCR6 Deficiency Impairs IgA Production and Dysregulates Antimicrobial Peptide
      Production, Altering the Intestinal Flora.
AB  - Intestinal immunity exists as a complex relationship among immune cells,
      epithelial cells, and microbiota. CCR6 and its ligand-CCL20 are highly expressed
      in intestinal mucosal tissues, such as Peyer's patches (PPs) and isolated
      lymphoid follicles (ILFs). In this study, we investigated the role of the CCR6
      CCL20 axis in intestinal immunity under homeostatic conditions. CCR6 deficiency
      intrinsically affects germinal center reactions in PPs, leading to impairments in
      IgA class switching, IgA affinity, and IgA memory B cell production and
      positioning in PPs, suggesting an important role for CCR6 in T-cell-dependent IgA
      generation. CCR6 deficiency impairs the maturation of ILFs. In these follicles,
      group 3 innate lymphoid cells are important components and a major source of IL
      22, which stimulates intestinal epithelial cells (IECs) to produce antimicrobial
      peptides (AMPs). We found that CCR6 deficiency reduces IL-22 production, likely
      due to diminished numbers of group 3 innate lymphoid cells within small-sized
      ILFs. The reduced IL-22 levels subsequently decrease the production of AMPs,
      suggesting a critical role for CCR6 in innate intestinal immunity. Finally, we
      found that CCR6 deficiency impairs the production of IgA and AMPs, leading to
      increased levels of Alcaligenes in PPs, and segmented filamentous bacteria in
      IECs. Thus, the CCR6-CCL20 axis plays a crucial role in maintaining intestinal
      symbiosis by limiting the overgrowth of mucosa-associated commensal bacteria.

PMID- 28744288
TI  - Naltrexone Inhibits IL-6 and TNFalpha Production in Human Immune Cell Subsets
      following Stimulation with Ligands for Intracellular Toll-Like Receptors.
AB  - The opioid antagonist naltrexone hydrochloride has been suggested to be a
      potential therapy at low dosage for multiple inflammatory conditions and cancers.
      Little is known about the immune-modulating effects of naltrexone, but an effect
      on the activity of toll-like receptor 4 (TLR4) has been reported. We analyzed the
      effects of naltrexone hydrochloride on IL-6 secretion by peripheral blood
      mononuclear cells (PBMC) in vitro following stimulation with ligands for TLR4 and
      for the intracellular receptors TLR7, TLR8, and TLR9. Naltrexone did not affect
      cell viability or induce apoptosis of PBMC. Intracellular staining demonstrated
      that naltrexone inhibited production of IL-6 and TNFalpha by monocyte and
      plasmacytoid dendritic cell subsets within the PBMC population following
      treatment with ligands for TLR7/8 and TLR9, respectively. No effect of cytokine
      production by PBMC following stimulation of TLR4 was observed. Additionally,
      naltrexone inhibited IL-6 production in isolated monocytes and B cells after
      TLR7/8 and TLR9 stimulation, respectively, but no effect on IL-6 production in
      isolated monocytes after TLR4 stimulation was observed. These findings indicate
      that naltrexone has the potential to modulate the secretion of inflammatory
      cytokines in response to intracellular TLR activity, supporting the hypothesis
      that it may have potential for use as an immunomodulator.

PMID- 28744289
TI  - Identification of QTL Associated with Nitrogen Uptake and Nitrogen Use Efficiency
      Using High Throughput Genotyped CSSLs in Rice (Oryza sativa L.).
AB  - Nitrogen (N) availability is a major factor limiting crop growth and development.
      Identification of quantitative trait loci (QTL) for N uptake (NUP) and N use
      efficiency (NUE) can provide useful information regarding the genetic basis of
      these traits and their associated effects on yield production. In this study, a
      set of high throughput genotyped chromosome segment substitution lines (CSSLs)
      derived from a cross between recipient 9311 and donor Nipponbare were used to
      identify QTL for rice NUP and NUE. Using high throughput sequencing, each CSSL
      were genotyped and an ultra-high-quality physical map was constructed. A total of
      13 QTL, seven for NUP and six for NUE, were identified in plants under hydroponic
      culture with all nutrients supplied in sufficient quantities. The proportion of
      phenotypic variation explained by these QTL for NUP and NUE ranged from 3.16
      13.99% and 3.76-12.34%, respectively. We also identified several QTL for biomass
      yield (BY) and grain yield (GY), which were responsible for 3.21-45.54% and 6.28
      7.31%, respectively, of observed phenotypic variation. GY were significantly
      positively correlated with NUP and NUE, with NUP more closely correlated than
      NUE. Our results contribute information to NUP and NUE improvement in rice.

PMID- 28744291
TI  - A Model of Silicon Dynamics in Rice: An Analysis of the Investment Efficiency of
      Si Transporters.
AB  - Silicon is the second most abundant element in soils and is beneficial for plant
      growth. Although, the localizations and polarities of rice Si transporters have
      been elucidated, the mechanisms that control the expression of Si transporter
      genes and the functional reasons for controlling expression are not well
      understood. We developed a new model that simulates the dynamics of Si in the
      whole plant in rice by considering Si transport in the roots, distribution at the
      nodes, and signaling substances controlling transporter gene expression. To
      investigate the functional reason for the diurnal variation of the expression
      level, we compared investment efficiencies (the amount of Si accumulated in the
      upper leaf divided by the total expression level of Si transporter genes) at
      different model settings. The model reproduced the gradual decrease and diurnal
      variation of the expression level of the transporter genes observed by previous
      experimental studies. The results of simulation experiments showed that a
      considerable reduction in the expression of Si transporter genes during the night
      increases investment efficiency. Our study suggests that rice has a system that
      maximizes the investment efficiency of Si uptake.

PMID- 28744290
TI  - Photoreceptor Mediated Plant Growth Responses: Implications for Photoreceptor
      Engineering toward Improved Performance in Crops.
AB  - Rising temperatures during growing seasons coupled with altered precipitation
      rates presents a challenging task of improving crop productivity for overcoming
      such altered weather patterns and cater to a growing population. Light is a
      critical environmental factor that exerts a powerful influence on plant growth
      and development ranging from seed germination to flowering and fruiting. Higher
      plants utilize a suite of complex photoreceptor proteins to perceive surrounding
      red/far-red (phytochromes), blue/UV-A (cryptochromes, phototropins,
      ZTL/FKF1/LKP2), and UV-B light (UVR8). While genomic studies have also shown that
      light induces extensive reprogramming of gene expression patterns in plants,
      molecular genetic studies have shown that manipulation of one or more
      photoreceptors can result in modification of agronomically beneficial traits.
      Such information can assist researchers to engineer photoreceptors via genome
      editing technologies to alter expression or even sensitivity thresholds of native
      photoreceptors for targeting aspects of plant growth that can confer superior
      agronomic value to the engineered crops. Here we summarize the agronomically
      important plant growth processes influenced by photoreceptors in crop species,
      alongwith the functional interactions between different photoreceptors and
      phytohormones in regulating these responses. We also discuss the potential
      utility of synthetic biology approaches in photobiology for improving
      agronomically beneficial traits of crop plants by engineering designer
      photoreceptors.

PMID- 28744292
TI  - Xylem and Leaf Functional Adjustments to Drought in Pinus sylvestris and Quercus
      pyrenaica at Their Elevational Boundary.
AB  - Climatic scenarios for the Mediterranean region forecast increasing frequency and
      intensity of drought events. Consequently, a reduction in Pinus sylvestris L.
      distribution range is projected within the region, with this species being
      outcompeted at lower elevations by more drought-tolerant taxa such as Quercus
      pyrenaica Willd. The functional response of these species to the projected shifts
      in water availability will partially determine their performance and, thus, their
      competitive success under these changing climatic conditions. We studied how the
      cambial and leaf phenology and xylem anatomy of these two species responded to a
      3-year rainfall exclusion experiment set at their elevational boundary in Central
      Spain. Additionally, P. sylvestris leaf gas exchange, water potential and carbon
      isotope content response to the treatment were measured. Likewise, we assessed
      inter-annual variability in the studied functional traits under control and
      rainfall exclusion conditions. Prolonged exposure to drier conditions did not
      affect the onset of xylogenesis in either of the studied species, whereas xylem
      formation ceased 1-3 weeks earlier in P. sylvestris. The rainfall exclusion had,
      however, no effect on leaf phenology on either species, which suggests that
      cambial phenology is more sensitive to drought than leaf phenology. P. sylvestris
      formed fewer, but larger tracheids under dry conditions and reduced the
      proportion of latewood in the tree ring. On the other hand, Q. pyrenaica did not
      suffer earlywood hydraulic diameter changes under rainfall exclusion, but
      experienced a cumulative reduction in latewood width, which could ultimately
      challenge its hydraulic performance. The phenological and anatomical response of
      the studied species to drought is consistent with a shift in resource allocation
      under drought stress from xylem to other sinks. Additionally, the tighter
      stomatal control and higher intrinsic water use efficiency observed in drought
      stressed P. sylvestris may eventually limit carbon uptake in this species. Our
      results suggest that both species are potentially vulnerable to the forecasted
      increase in drought stress, although P. sylvestris might experience a higher risk
      of drought-induced decline at its low elevational limit.

PMID- 28744293
TI  - TOR-Dependent and -Independent Pathways Regulate Autophagy in Arabidopsis
      thaliana.
AB  - Autophagy is a critical process for recycling of cytoplasmic materials during
      environmental stress, senescence and cellular remodeling. It is upregulated under
      a wide range of abiotic stress conditions and is important for stress tolerance.
      Autophagy is repressed by the protein kinase target of rapamycin (TOR), which is
      activated in response to nutrients and in turn upregulates cell growth and
      translation and inhibits autophagy. Down-regulation of TOR in Arabidopsis
      thaliana leads to constitutive autophagy and to decreased growth, but the
      relationship to stress conditions is unclear. Here, we assess the extent to which
      TOR controls autophagy activation by abiotic stress. Overexpression of TOR
      inhibited autophagy activation by nutrient starvation, salt and osmotic stress,
      indicating that activation of autophagy under these conditions requires down
      regulation of TOR activity. In contrast, TOR overexpression had no effect on
      autophagy induced by oxidative stress or ER stress, suggesting that activation of
      autophagy by these conditions is independent of TOR function. The plant hormone
      auxin has been shown previously to up-regulate TOR activity. To confirm the
      existence of two pathways for activation of autophagy, dependent on the stress
      conditions, auxin was added exogenously to activate TOR, and the effect on
      autophagy under different conditions was assessed. Consistent with the effect of
      TOR overexpression, the addition of the auxin NAA inhibited autophagy during
      nutrient deficiency, salt and osmotic stress, but not during oxidative or ER
      stress. NAA treatment was unable to block autophagy induced by a TOR inhibitor or
      by a mutation in the TOR complex component RAPTOR1B, indicating that auxin is
      upstream of TOR in the regulation of autophagy. We conclude that repression of
      auxin-regulated TOR activity is required for autophagy activation in response to
      a subset of abiotic stress conditions.

PMID- 28744294
TI  - Transcriptome Profiling Using Single-Molecule Direct RNA Sequencing Approach for
      In-depth Understanding of Genes in Secondary Metabolism Pathways of Camellia
      sinensis.
AB  - Characteristic secondary metabolites, including flavonoids, theanine and
      caffeine, are important components of Camellia sinensis, and their biosynthesis
      has attracted widespread interest. Previous studies on the biosynthesis of these
      major secondary metabolites using next-generation sequencing technologies limited
      the accurately prediction of full-length (FL) splice isoforms. Herein, we applied
      single-molecule sequencing to pooled tea plant tissues, to provide a more
      complete transcriptome of C. sinensis. Moreover, we identified 94 FL transcripts
      and four alternative splicing events for enzyme-coding genes involved in the
      biosynthesis of flavonoids, theanine and caffeine. According to the comparison
      between long-read isoforms and assemble transcripts, we improved the quality and
      accuracy of genes sequenced by short-read next-generation sequencing technology.
      The resulting FL transcripts, together with the improved assembled transcripts
      and identified alternative splicing events, enhance our understanding of genes
      involved in the biosynthesis of characteristic secondary metabolites in C.
      sinensis.

PMID- 28744295
TI  - Antarctic Moss Multiprotein Bridging Factor 1c Overexpression in Arabidopsis
      Resulted in Enhanced Tolerance to Salt Stress.
AB  - Polytrichastrum alpinum is one of the moss species that survives extreme
      conditions in the Antarctic. In order to explore the functional benefits of moss
      genetic resources, P. alpinum multiprotein-bridging factor 1c gene (PaMBF1c) was
      isolated and characterized. The deduced amino acid sequence of PaMBF1c comprises
      of a multiprotein-bridging factor (MBF1) domain and a helix-turn-helix (HTH)
      domain. PaMBF1c expression was induced by different abiotic stresses in P.
      alpinum, implying its roles in stress responses. We overexpressed PaMBF1c in
      Arabidopsis and analyzed the resulting phenotypes in comparison with wild type
      and/or Arabidopsis MBF1c (AtMBF1c) overexpressors. Overexpression of PaMBF1c in
      Arabidopsis resulted in enhanced tolerance to salt and osmotic stress, as well as
      to cold and heat stress. More specifically, enhanced salt tolerance was observed
      in PaMBF1c overexpressors in comparison to wild type but not clearly observable
      in AtMBF1c overexpressing lines. Thus, these results implicate the evolution of
      PaMBF1c under salt-enriched Antarctic soil. RNA-Seq profiling of NaCl-treated
      plants revealed that 10 salt-stress inducible genes were already up-regulated in
      PaMBF1c overexpressing plants even before NaCl treatment. Gene ontology
      enrichment analysis with salt up-regulated genes in each line uncovered that the
      terms lipid metabolic process, ion transport, and cellular amino acid
      biosynthetic process were significantly enriched in PaMBF1c overexpressors.
      Additionally, gene enrichment analysis with salt down-regulated genes in each
      line revealed that the enriched categories in wild type were not significantly
      overrepresented in PaMBF1c overexpressing lines. The up-regulation of several
      genes only in PaMBF1c overexpressing lines suggest that enhanced salt tolerance
      in PaMBF1c-OE might involve reactive oxygen species detoxification, maintenance
      of ATP homeostasis, and facilitation of Ca2+ signaling. Interestingly, many salt
      down-regulated ribosome- and translation-related genes were not down-regulated in
      PaMBF1c overexpressing lines under salt stress. These differentially regulated
      genes by PaMBF1c overexpression could contribute to the enhanced tolerance in
      PaMBF1c overexpressing lines under salt stress.

PMID- 28744296
TI  - Metabolomic Analysis of Alfalfa (Medicago sativa L.) Root-Symbiotic Rhizobia
      Responses under Alkali Stress.
AB  - Alkaline salts (e.g., NaHCO3 and Na2CO3) causes more severe morphological and
      physiological damage to plants than neutral salts (e.g., NaCl and Na2SO4) due to
      differences in pH. The mechanism by which plants respond to alkali stress is not
      fully understood, especially in plants having symbotic relationships such as
      alfalfa (Medicago sativa L.). Therefore, a study was designed to evaluate the
      metabolic response of the root-nodule symbiosis in alfalfa under alkali stress
      using comparative metabolomics. Rhizobium-nodulized (RI group) and non-nodulized
      (NI group) alfalfa roots were treated with 200 mmol/L NaHCO3 and, roots samples
      were analyzed for malondialdehydyde (MDA), proline, glutathione (GSH), superoxide
      dismutase (SOD), and peroxidase (POD) content. Additionally, metabolite profiling
      was conducted using gas chromatography combined with time-of-flight mass
      spectrometry (GC/TOF-MS). Phenotypically, the RI alfalfa exhibited a greater
      resistance to alkali stress than the NI plants examined. Physiological analysis
      and metabolic profiling revealed that RI plants accumulated more antioxidants
      (SOD, POD, GSH), osmolytes (sugar, glycols, proline), organic acids (succinic
      acid, fumaric acid, and alpha-ketoglutaric acid), and metabolites that are
      involved in nitrogen fixation. Our pairwise metabolomics comparisons revealed
      that RI alfalfa plants exhibited a distinct metabolic profile associated with
      alkali putative tolerance relative to NI alfalfa plants. Data provide new
      information about the relationship between non-nodulized, rhizobium-nodulized
      alfalfa and alkali resistance.

PMID- 28744297
TI  - DEWAX Transcription Factor Is Involved in Resistance to Botrytis cinerea in
      Arabidopsis thaliana and Camelina sativa.
AB  - The cuticle of land plants is the first physical barrier to protect their aerial
      parts from biotic and abiotic stresses. DEWAX, an AP2/ERF-type transcription
      factor, negatively regulates cuticular wax biosynthesis. In this study, we
      investigated the resistance to Botrytis cinerea in Arabidopsis thaliana and
      Camelina sativa overexpressing DEWAX and in Arabidopsis dewax mutant. Compared to
      wild type (WT) leaves, Arabidopsis DEWAX OX and dewax leaves were more and less
      permeable to toluidine blue dye, respectively. The ROS levels increased in DEWAX
      OX leaves, but decreased in dewax relative to WT leaves. Compared to WT, DEWAX OX
      was more resistant, while dewax was more sensitive to B. cinerea; however,
      defense responses to Pseudomonas syringae pv. tomato DC3000:GFP were inversely
      modulated. Microarray and RT-PCR analyses indicated that the expression of
      defense-related genes was upregulated in DEWAX OX, but downregulated in dewax
      relative to WT. Transactivation assay showed that DEWAX upregulated the
      expression of PDF1.2a, IGMT1, and PRX37. Chromatin immunoprecipitation assay
      revealed that DEWAX directly interacts with the GCC-box motifs of PDF1.2a
      promoter. In addition, ectopic expression of DEWAX increased the tolerance to B.
      cinerea in C. sativa. Taken together, we suggest that increased ROS accumulation
      and DEWAX-mediated upregulation of defense-related genes are closely associated
      with enhanced resistance to B. cinerea in Arabidopsis and C. sativa.

PMID- 28744298
TI  - Poaceae vs. Abiotic Stress: Focus on Drought and Salt Stress, Recent Insights and
      Perspectives.
AB  - Poaceae represent the most important group of crops susceptible to abiotic
      stress. This large family of monocotyledonous plants, commonly known as grasses,
      counts several important cultivated species, namely wheat (Triticum aestivum),
      rice (Oryza sativa), maize (Zea mays), and barley (Hordeum vulgare). These crops,
      notably, show different behaviors under abiotic stress conditions: wheat and rice
      are considered sensitive, showing serious yield reduction upon water scarcity and
      soil salinity, while barley presents a natural drought and salt tolerance. During
      the green revolution (1940-1960), cereal breeding was very successful in
      developing high-yield crops varieties; however, these cultivars were maximized
      for highest yield under optimal conditions, and did not present suitable traits
      for tolerance under unfavorable conditions. The improvement of crop abiotic
      stress tolerance requires a deep knowledge of the phenomena underlying tolerance,
      to devise novel approaches and decipher the key components of agricultural
      production systems. Approaches to improve food production combining both enhanced
      water use efficiency (WUE) and acceptable yields are critical to create a
      sustainable agriculture in the future. This paper analyzes the latest results on
      abiotic stress tolerance in Poaceae. In particular, the focus will be directed
      toward various aspects of water deprivation and salinity response efficiency in
      Poaceae. Aspects related to cell wall metabolism will be covered, given the
      importance of the plant cell wall in sensing environmental constraints and in
      mediating a response; the role of silicon (Si), an important element for
      monocots' normal growth and development, will also be discussed, since it
      activates a broad-spectrum response to different exogenous stresses. Perspectives
      valorizing studies on landraces conclude the survey, as they help identify key
      traits for breeding purposes.

PMID- 28744299
TI  - Responses of Nitrogen Metabolism, Uptake and Translocation of Maize to
      Waterlogging at Different Growth Stages.
AB  - We performed a field experiment using the maize hybrids DengHai605 (DH605) and
      ZhengDan958 (ZD958) to study nitrogen uptake and translocation, key enzyme
      activities of nitrogen metabolism in response to waterlogging at the third leaf
      stage (V3), the sixth leaf stage (V6), and the 10th day after the tasseling stage
      (10VT). Results showed that N accumulation amount was significantly reduced after
      waterlogging, most greatly in the V3 waterlogging treatment (V3-W), with
      decreases of 41 and 37% in DH605 and ZD958, respectively. N accumulation in each
      organ and N allocation proportions in grains decreased significantly after
      waterlogging, whereas N allocation proportions increased in stem and leaf. The
      reduction in stem and leaf N accumulation after waterlogging was mainly caused by
      a decrease in dry matter accumulation, and a reduction in N translocation from
      stems and leaves to grains after waterlogging. Additionally, waterlogging
      decreased the activity of key N metabolism enzymes (nitrate reductase, glutamine,
      glutamate synthase, and glutamate dehydrogenase), and the most significant
      reduction in V3-W with a decrease of 59, 46, 35, and 26% for DH605, and 60, 53,
      31, and 25 for ZD958, respectively. Waterlogging disrupted N metabolism, hindered
      N absorption and transportation, and decreased maize yield.

PMID- 28744300
TI  - Metabolic Effects of Acibenzolar-S-Methyl for Improving Heat or Drought Stress in
      Creeping Bentgrass.
AB  - Acibenzolar-S-methyl (ASM) is a synthetic functional analog of salicylic acid
      which can induce systemic acquired resistance in plants, but its effects on
      abiotic stress tolerance is not well known. The objectives of this study were to
      examine effects of acibenzolar-S-methyl on heat or drought tolerance in creeping
      bentgrass (Agrostis stolonifera) and to determine major ASM-responsive
      metabolites and proteins associated with enhanced abiotic stress tolerance.
      Creeping bentgrass plants (cv. 'Penncross') were foliarly sprayed with ASM and
      were exposed to non-stress (20/15 degrees C day/night), heat stress (35/30
      degrees C), or drought conditions (by withholding irrigation) in controlled
      environment growth chambers. Exogenous ASM treatment resulted in improved heat or
      drought tolerance, as demonstrated by higher overall turf quality, relative water
      content, and chlorophyll content compared to the untreated control. Western
      blotting revealed that ASM application resulted in up-regulation of ATP synthase,
      HSP-20, PR-3, and Rubisco in plants exposed to heat stress, and greater
      accumulation of dehydrin in plants exposed to drought stress. Metabolite
      profiling identified a number of amino acids, organic acids, and sugars which
      were differentially accumulated between ASM treated and untreated plants under
      heat or drought stress, including aspartic acid, glycine, citric acid, malic
      acid, and the sugars glucose, and fructose. Our results suggested that ASM was
      effective in improving heat or drought tolerance in creeping bentgrass, mainly
      through enhancing protein synthesis and metabolite accumulation involved in
      osmotic adjustment, energy metabolism, and stress signaling.

PMID- 28744301
TI  - Three-Dimensional Evaluation on Ecotypic Diversity of Traditional Chinese
      Medicine: A Case Study of Artemisia annua L.
AB  - Artemisinin is the first-line drug for anti-malaria recommended by the World
      Health Organization (WHO). As the sole natural plant source of artemisinin,
      ecotypes of Artemisia annua L. vary widely in artemisinin content between
      nations, and China is the main producing area of A. annua. Here we present a
      three-dimensional evaluation on ecotypic diversity of A. annua from 12 main
      producing areas in China using high-performance liquid chromatography coupled
      with evaporative light scattering detection (HPLC-ELSD) method, DNA barcoding and
      ecological analyses. The results indicated that A. annua exhibited high ecotypic
      diversity. A. annua grown in the South of the Qinling Mountains-Huaihe River Line
      had a high artemisinin content, whereas the northern ones were low. Similar
      pattern was noted in the genetic diversity. The southern A. annua had high
      intraspecific variation in contrast to the northern A. annua. In terms of
      ecological analyses, humidity and sunshine time could be the major limiting
      ecological factors that affect the accumulation of artemisinin. This is the first
      reported three-dimensional evaluation integrating chemical, molecular and
      ecological analyses of the ecotypic diversity of A. annua. The work will
      facilitate exploring the genetic basis of chemical variations and developing
      strategies for the breeding and cultivation of high quality A. annua.

PMID- 28744302
TI  - Nitrogen Fertilizer Deep Placement for Increased Grain Yield and Nitrogen
      Recovery Efficiency in Rice Grown in Subtropical China.
AB  - Field plot experiments were conducted over 3 years (from April 2014 to November
      2016) in a double-rice (Oryza sativa L.) cropping system in subtropical China to
      evaluate the effects of N fertilizer placement on grain yield and N recovery
      efficiency (NRE). Different N application methods included: no N application
      (CK); N broadcast application (NBP); N and NPK deep placement (NDP and NPKDP,
      respectively). Results showed that grain yield and apparent NRE significantly
      increased for NDP and NPKDP as compared to NBP. The main reason was that N deep
      placement (NDP) increased the number of productive panicle per m-2. To further
      evaluate the increase, a pot experiment was conducted to understand the N supply
      in different soil layers in NDP during the whole rice growing stage and a 15N
      tracing technique was used in a field experiment to investigate the fate of urea
      15N in the rice-soil system during rice growth and at maturity. The pot
      experiment indicated that NDP could maintain a higher N supply in deep soil
      layers than N broadcast for 52 days during rice growth. The 15N tracing study
      showed that NDP could maintain much higher fertilizer N in the 5-20 cm soil layer
      during rice growth and could induce plant to absorb more N from fertilizer and
      soil than NBP, which led to higher NRE. One important finding was that NDP and
      NPKDP significantly increased fertilizer NRE but did not lead to N declined in
      soil compared to NBP. Compared to NPK, NPKDP induced rice plants to absorb more
      fertilizer N rather than soil N.

PMID- 28744303
TI  - Corrigendum: Transcriptomic Analysis in Strawberry Fruits Reveals Active Auxin
      Biosynthesis and Signaling in the Ripe Receptacle.
AB  - [This corrects the article on p. 889 in vol. 8, PMID: 28611805.].

PMID- 28744304
TI  - Corrigendum to "Automatic Characterization of the Physiological Condition of the
      Carotid Artery in 2D Ultrasound Image Sequences Using Spatiotemporal and
      Spatiospectral 2D Maps".
AB  - [This corrects the article DOI: 10.1155/2014/876267.].

PMID- 28744305
TI  - MultiP-Apo: A Multilabel Predictor for Identifying Subcellular Locations of
      Apoptosis Proteins.
AB  - Apoptosis proteins play an important role in the mechanism of programmed cell
      death. Predicting subcellular localization of apoptosis proteins is an essential
      step to understand their functions and identify drugs target. Many computational
      prediction methods have been developed for apoptosis protein subcellular
      localization. However, these existing works only focus on the proteins that have
      one location; proteins with multiple locations are either not considered or
      assumed as not existing when constructing prediction models, so that they cannot
      completely predict all the locations of the apoptosis proteins with multiple
      locations. To address this problem, this paper proposes a novel multilabel
      predictor named MultiP-Apo, which can predict not only apoptosis proteins with
      single subcellular location but also those with multiple subcellular locations.
      Specifically, given a query protein, GO-based feature extraction method is used
      to extract its feature vector. Subsequently, the GO feature vector is classified
      by a new multilabel classifier based on the label-specific features. It is the
      first multilabel predictor ever established for identifying subcellular locations
      of multilocation apoptosis proteins. As an initial study, MultiP-Apo achieves an
      overall accuracy of 58.49% by jackknife test, which indicates that our proposed
      predictor may become a very useful high-throughput tool in this area.

PMID- 28744306
TI  - Prevalence and Clinical Profile of Drug Eruptions among Antiretroviral Therapy
      Exposed HIV Infected People in Yaounde, Cameroon.
AB  - BACKGROUND: Prevalence and incidence of drug eruptions vary around the world and
      are influenced by some key factors including HIV infection. OBJECTIVE: This study
      aimed to find the peculiarities of drug eruptions in people living with HIV
      (PLHIV) and on antiretroviral therapy (ART). METHODS: This was a retrospective
      cross-sectional study including ART-taking PLHIV, aged 15+ years, followed up
      between January 2010 and December 2014 at the day-care unit of the Yaounde
      Central Hospital, and who presented with drug eruptions after ART initiation.
      RESULTS: Of 6,829 ART-experiencing PLHIV, 41 presented with drug eruptions,
      giving a prevalence of 0.6%. The M/F sex ratio equaled 0.17. The mean age was
      41.07 +/- 11.36 years. Benign drug eruptions accounted for 83.3%. Milder forms
      were essentially maculopapular exanthema (36.6%), fixed pigmented erythema
      (7.3%), and urticaria (4.9%). Severe forms were represented by multiform erythema
      (4.9%), toxic epidermal necrolysis (2.4%), and drug hypersensitivity syndrome
      (2.4%). The Zidovudine + Lamivudine + Efavirenz ART-protocol was received by
      48.8% of patients and 69% of patients were receiving Cotrimoxazole prophylaxis.
      Nevirapine, Efavirenz, Zidovudine, and Cotrimoxazole were suspected as the
      potential causes in 43.7%, 4.8%, 2.4%, and 26.8% of cases, respectively.
      CONCLUSION: Drug eruptions seem infrequent among ART-exposed HIV infected adult
      Cameroonians.

PMID- 28744307
TI  - Epithelial-Mesenchymal Transition Phenotype, Metformin, and Survival for
      Colorectal Cancer Patients with Diabetes Mellitus II.
AB  - OBJECTIVES: We aimed to explore the association between metformin treatment and
      epithelial-mesenchymal transition (EMT) phenotype and further appraise the
      prognostic values of metformin and EMT markers E-cadherin and vimentin for
      colorectal cancer (CRC) in clinical practice. METHODS: We collected specimens and
      evaluated clinicopathological parameters of 102 stage I to III CRC patients with
      prediagnosed type 2 diabetes mellitus (DM II). Expression of E-cadherin and
      vimentin in tumors was detected by immunohistochemistry (IHC), and statistical
      analysis was performed using SPSS 19.0. RESULTS: In correlation tests, we found a
      lower tumor cell EMT degree (more E-cadherin (P = 0.014) and less vimentin (P =
      0.011) expression in patients who used metformin, and the expression of E
      cadherin and vimentin was associated with serum CA19-9 (P = 0.048, P = 0.009),
      tumor invasive depth (T) (P < 0.001, P = 0.045), and lymph invasion (N) (P =
      0.013, P = 0.001). In Cox multivariate regression analysis, E-cadherin was
      identified as a prognostic factor for disease-free survival (DFS) (P = 0.038) and
      metformin use (P = 0.015P = 0.044) and lymph invasion (P = 0.016P = 0.023) were
      considered as the prognostic factors for both DFS and overall survival (OS).
      CONCLUSION: Our study suggested that metformin may impede the EMT process and
      improve survival for stage I-III CRC patients with DM II.

PMID- 28744308
TI  - Recent Pathophysiological Aspects of Peyronie's Disease: Role of Free Radicals,
      Rationale, and Therapeutic Implications for Antioxidant Treatment-Literature
      Review.
AB  - Peyronie's disease (PD) is a chronic inflammation of tunica albuginea of the
      corpora cavernosa that causes an inelastic plaque resulting in penis deformation.
      Although its etiology is not completely known, there is general consensus that PD
      is genetically transmitted and secondary to penile trauma. In recent years,
      numerous studies demonstrated the role played by oxidative stress in PD
      pathogenesis, and other studies have described successful use of antioxidants in
      PD treatment. Oxidative stress is an integral part of this disease, influencing
      its progression. In the early stages of PD, the inflammatory infiltrate cells
      produce high quantities of free radicals and proinflammatory and profibrotic
      cytokines, with consequent activation of transcription factor NF-kappaB. While
      conservative therapies commonly used in the early stages of PD include oral
      substances (Potaba, tamoxifen, colchicine, and vitamin E), intralesional
      treatment (verapamil, interferon, steroids, and more recently collagenase
      clostridium histolyticum-Xiaflex), and local physical treatment (iontophoresis,
      extracorporeal shock wave therapy, and penile extender), the significant results
      obtained by emerging treatments with the antioxidants cited in this article
      suggest these therapeutic agents interfere at several levels with the disease's
      pathogenetic mechanisms. Antioxidants therapy outcomes are interesting for good
      clinical practice and also confirm the fundamental role played by oxidative
      stress in PD.

PMID- 28744309
TI  - GH Responsiveness to Combined GH-Releasing Hormone and Arginine Administration in
      Obese Patients with Fibromyalgia Syndrome.
AB  - Reportedly, fibromyalgia (FM) is frequently associated with reduced IGF-1 levels
      and GH hyporesponsiveness to different GH stimulation tests. Since there is a
      high prevalence of obesity in FM, and obesity itself is characterized by
      hyposomatotropism, the aim of this study was to assess IGF-1 levels and GH
      responsiveness in sixteen severely obese women suffering from FM, who, subdivided
      into two subgroups on the basis of their age-dependent IGF-1 values (> or <-2
      SDS), underwent the combined GHRH plus arginine test. Four out of 16 obese women
      with FM (25%) had low IGF-1 SDS values, 2 cases of this subgroup (12.5%) failing
      also to normally respond to the test. Among patients with normal GH responses, 4
      showed a delayed GH peak. The subgroup with low IGF-1 SDS values had higher BMI
      than that with normal IGF-1 SDS. GH peak and area under the curve were not
      correlated with CRP, ESR, or tender point score, while significant correlations
      were found with fat-free mass and fat mass. In conclusion, this study shows the
      existence of a high prevalence of GH-IGF-1 dysfunction in patients with both FM
      and obesity, presumably as a consequence of the obese rather than fibromyalgic
      condition.

PMID- 28744310
TI  - Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and
      Carcinoembryonic Antigen Levels in Diabetic Nephropathy.
AB  - OBJECTIVE: We aimed to explore whether squamous cell carcinoma antigen (SCC),
      cytokeratin 19 fragment (Cyfra21-1), neuron-specific enolase (NSE), and
      carcinoembryonic antigen (CEA) are elevated in diabetic nephropathy (DN) and the
      association between urinary albumin-to-creatinine ratio (UACR) and tumor markers
      in diabetic patients. METHODS: Nondialysis patients with diabetes (n = 261) and
      90 healthy controls were enrolled. DN was defined as an UACR >= 30 mg/g in the
      absence of a urinary tract infection or other renal abnormalities. RESULTS:
      Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels
      than those with normoalbuminuria and healthy controls. The rates of positive SCC,
      Cyfra21-1, and CEA significantly increased with increasing urinary albumin
      excretion (all P for trend < 0.001). In contrast, NSE was not affected by DN.
      SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR.
      In logistic regression, after multivariable adjustment, increased UACR was
      associated with increased odds ratio of elevated tumor marker levels (all P for
      trend < 0.05). CONCLUSIONS: Serum levels of SCC, Cyfra21-1, and CEA are markedly
      increased with increasing urinary albumin excretion, which affects the
      specificity for diagnosis for lung cancer. Appropriate interpretation of tumor
      markers in diabetic patients is mandatory to avoid unnecessary and even hazardous
      biopsies.

PMID- 28744311
TI  - Type 2 Diabetes and Cardiovascular Risk in Women 2016.

PMID- 28744312
TI  - Prevalence of EGFR Mutations in Lung Cancer in Uruguayan Population.
AB  - BACKGROUND: Incorporation of molecular analysis of the epidermal growth factor
      receptor (EGFR) gene into routine clinical practice represents a milestone for
      personalized therapy of the non-small-cell lung cancer (NSCLC). However, the
      genetic testing of EGFR mutations has not yet become a routine clinical practice
      in developing countries. In view of different prevalence of such mutations among
      different ethnicities and geographic regions, as well as the limited existing
      data from Latin America, our aim was to study the frequency of major types of
      activating mutations of the EGFR gene in NSCLC patients from Uruguay. METHODS: We
      examined EGFR mutations in exons 18 through 21 in 289 NSCLC Uruguayan patients by
      PCR-direct sequencing. RESULTS: EGFR mutations were detected in 53 of the 289
      (18.3%) patients, more frequently in women (23.4%) than in men (14.5%). The
      distribution by exon was similar to that generally reported in the literature.
      CONCLUSIONS: This first epidemiological study of EGFR mutations in Uruguay
      reveals a wide spectrum of mutations and an overall prevalence of 18.3%. The
      background ethnic structure of the Uruguayan population could play an important
      role in explaining our findings.

PMID- 28744313
TI  - The Prevalence and Risk Factors for Low Birth Weight among Term Newborns in Adwa
      General Hospital, Northern Ethiopia.
AB  - Background. World health organization estimates that 25 million LBW babies are
      born annually worldwide and 95% occur in developing countries. Objective. To
      assess the prevalence and associated factors of low birth weight among term
      neonates delivered in Adwa Hospital, Northern Ethiopia. Methods. A cross
      sectional study was conducted among neonates delivered in Adwa Hospital. All live
      births delivered from July 1, 2014, to June 30, 2016, were included in this
      study. The study participants were selected through systematic sampling technique
      and the data was collected using a structured questionnaire. Data was entered to
      Epi Data version 3.1 and analyzed using SPSS version 20 software. To identify
      independent predictors, bivariate and multivariable binary logistic regressions
      were employed. Adjusted odds ratio and 95% confidence interval were used to
      determine the strength of association. Results. The prevalence of term low birth
      weight was 10%. The risk factors were mothers aged less than 20 years, mothers
      whose pregnancy was desired, mothers with a history of abortion, and mothers with
      normal hemoglobin, iron with folic acid, and HIV status. Conclusion. The burden
      of LBW obtained in this study was in the same range as in some other countries.

PMID- 28744315
TI  - Targeting Adult Mesenchymal Stem Cells Plasticity for Tissue Regeneration.

PMID- 28744314
TI  - Changes of Bone Turnover Markers in Long Bone Nonunions Treated with a
      Regenerative Approach.
AB  - In this clinical trial, we investigated if biochemical bone turnover markers
      (BTM) changed according to the progression of bone healing induced by autologous
      expanded MSC combined with a biphasic calcium phosphate in patients with delayed
      union or nonunion of long bone fractures. Bone formation markers, bone resorption
      markers, and osteoclast regulatory proteins were measured by enzymatic
      immunoassay before surgery and after 6, 12, and 24 weeks. A satisfactory bone
      healing was obtained in 23 out of 24 patients. Nine subjects reached a good
      consolidation already at 12 weeks, and they were considered as the "early
      consolidation" group. We found that bone-specific alkaline phosphatase (BAP), C
      terminal propeptide of type I procollagen (PICP), and beta crosslaps collagen
      (CTX) changed after the regenerative treatment, BAP and CTX correlated to the
      imaging results collected at 12 and 24 weeks, and BAP variation along the healing
      course differed in patients who had an "early consolidation." A remarkable
      decrease in BAP and PICP was observed at all time points in a single patient who
      experienced a treatment failure, but the predictive value of BTM changes cannot
      be determined. Our findings suggest that BTM are promising tools for monitoring
      cell therapy efficacy in bone nonunions, but studies with larger patient numbers
      are required to confirm these preliminary results.

PMID- 28744316
TI  - The Antidepressant and Cognitive Improvement Activities of the Traditional
      Chinese Herb Cistanche.
AB  - More than ten percent of people suffer from at least one episode of depression
      and related mental disorders in a lifetime, and depression and related mental
      disorders are one of the world's greatest public health problems. A multiple
      system theory holds that dysregulation of the multiple systems underlies the
      pathogenesis of depression and related mental disorders, and new therapies based
      on the multiple system dysregulation theory are urgently needed. In this study,
      the antidepressant effect of decoction from herb Cistanche deserticola Y.C.Ma and
      Cistanche tubulosa was examined. Herb Cistanche decoction reduced the immobility
      period significantly in the mouse tail suspension test. Mice treated with herb
      decoction showed an improved ability of spatial learning and memory in the Morris
      water maze test. Groups treated herb decoction displayed a downregulated
      monoamine oxidase (MAO) activity; the dopamine (DA) concentration in the brain
      was upregulated, indicating herb Cistanche decoction improved the nerve
      excitability; the serum concentration of corticosterone (CORT) was downregulated,
      showing that mice benefited from a reduced stress level. Hence, the
      antidepressant efficacy and mechanism of traditional Chinese herb Cistanche were
      explored in this study. Herb Cistanche showed a potential to be developed as a
      complementary and alternative therapy for depression.

PMID- 28744317
TI  - Podophyllotoxin Extracted from Juniperus sabina Fruit Inhibits Rat Sperm
      Maturation and Fertility by Promoting Epididymal Epithelial Cell Apoptosis.
AB  - This study aimed to investigate the antifertility effect of Juniperus sabina
      fruit on male rats and its possible mechanism, and hence it might be developed as
      a potential nonhormonal male contraceptive. Male rats were intragastrically fed
      for consecutive 8-week and 4-week recovery with the fruit of J. Sabina, and sperm
      maturation, serum testosterone level, and histopathology were analyzed.
      Epididymal epithelial cell culture was prepared for detection of podophyllotoxin
      activities. Furthermore, cell proliferation, transmission electron microscopy,
      Annexin V/Propidium iodide, TUNEL, RT-PCR, ELISA, and western blotting were
      examined. The results showed that rat sperm motility and fertility were
      remarkably declined after feeding the fruit. Moreover, the fruit targeted the
      epididymis rather than the testis. After 4-week recovery, more than half of the
      male rats resumed normal fertility. It was found that podophyllotoxin
      significantly inhibited epididymal epithelial cell proliferation, promoted cell
      apoptosis, and increased the mRNA and protein levels of TNF-alpha and the
      expression levels of cytochrome c, caspase-8, caspase-9, and caspase-3. Our
      findings suggest that the fruit of J. sabina could inhibit male rat sperm
      maturation and fertility. The potential mechanism might be related to
      podophyllotoxin, inducing epididymal epithelial cell apoptosis through TNF-alpha
      and caspase signaling pathway.

PMID- 28744318
TI  - Optimization of Classification Strategies of Acetowhite Temporal Patterns towards
      Improving Diagnostic Performance of Colposcopy.
AB  - Efforts have been being made to improve the diagnostic performance of colposcopy,
      trying to help better diagnose cervical cancer, particularly in developing
      countries. However, improvements in a number of areas are still necessary, such
      as the time it takes to process the full digital image of the cervix, the
      performance of the computing systems used to identify different kinds of tissues,
      and biopsy sampling. In this paper, we explore three different, well-known
      automatic classification methods (k-Nearest Neighbors, Naive Bayes, and C4.5), in
      addition to different data models that take full advantage of this information
      and improve the diagnostic performance of colposcopy based on acetowhite temporal
      patterns. Based on the ROC and PRC area scores, the k-Nearest Neighbors and
      discrete PLA representation performed better than other methods. The values of
      sensitivity, specificity, and accuracy reached using this method were 60% (95% CI
      50-70), 79% (95% CI 71-86), and 70% (95% CI 60-80), respectively. The
      acetowhitening phenomenon is not exclusive to high-grade lesions, and we have
      found acetowhite temporal patterns of epithelial changes that are not
      precancerous lesions but that are similar to positive ones. These findings need
      to be considered when developing more robust computing systems in the future.

PMID- 28744319
TI  - [177Lu]pentixather: Comprehensive Preclinical Characterization of a First CXCR4
      directed Endoradiotherapeutic Agent.
AB  - Purpose: Based on the clinical relevance of the chemokine receptor 4 (CXCR4) as a
      molecular target in cancer and on the success of [68Ga]pentixafor as an imaging
      probe for high-contrast visualization of CXCR4-expression, the spectrum of
      clinical CXCR4-targeting was expanded towards peptide receptor radionuclide
      therapy (PRRT) by the development of [177Lu]pentixather. Experimental design:
      CXCR4 affinity, binding specificity, hCXCR4 selectivity and internalization
      efficiency of [177Lu]pentixather were evaluated using different human and murine
      cancer cell lines. Biodistribution studies (1, 6, 48, 96h and 7d p.i.) and in
      vivo metabolite analyses were performed using Daudi-lymphoma bearing SCID mice.
      Extrapolated organ doses were cross-validated with human dosimetry (pre
      therapeutic and during [177Lu]pentixather PRRT) in a patient with multiple
      myeloma (MM). Results: [177Lu]pentixather binds with high affinity, specificity
      and selectivity to hCXCR4 and shows excellent in vivo stability. Consequently,
      and supported by >96% plasma protein binding and a logP=-1.76, delaying whole
      body clearance of [177Lu]pentixather, tumor accumulation was high and persistent,
      both in the Daudi model and the MM patient. Tumor/background ratios (7d p.i.) in
      mice were 499+/-202, 33+/-7, 4.0+/-0.8 and 116+/-22 for blood, intestine, kidney
      and muscle, respectively. In the patient, high tumor/kidney and tumor/liver dose
      ratios of 3.1 and 6.4 were observed during [177Lu]pentixather PRRT (7.8 GBq),
      with the kidneys being the dose-limiting organs. Conclusions: [177Lu]pentixather
      shows excellent in vivo CXCR4-targeting characteristics and a suitable
      pharmacokinetic profile, leading to high tumor uptake and retention and thus high
      radiation doses to tumor tissue during PRRT, suggesting high clinical potential
      of this [68Ga]pentixafor/[177Lu]pentixather based CXCR4-targeted theranostic
      concept.

PMID- 28744320
TI  - Quantification of Tumor Vascular Permeability and Blood Volume by Positron
      Emission Tomography.
AB  - Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum
      albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye
      derived PET tracer, we aimed to establish a strategy for evaluating vascular
      permeability in malignant tumors via non-invasive PET. Experimental design: Sixty
      minute dynamic PET using [18F]FAl-NEB was performed in three xenograft tumor
      models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma
      and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the
      difference of the slopes between tumor and blood time-activity curve (TACs,
      expressed as Ps ). The method was further substantiated by EB extraction and
      colorimetric assay and correlates with that calculated from dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI). The changes in tumor vasculature
      at different time points were assessed with NEB PET in U-87 MG and UM-SCC-22B
      tumor models after treatment with bevacizumab or doxorubicin. Result: The Ps
      values calculated from tumor and blood TACs from multiple time-point static
      images are consistent with those from dynamic images. Moreover, the Ps showed a
      positive and significant correlation with extracted EB concentration and KPS-MRI
      generated from DCE-MRI, which further confirmed the soundness of this
      methodology. The antiangiogenic effect of bevacizumab could be revealed by NEB
      PET in U-87 MG tumors as early as 8 hrs after therapy, demonstrated by a
      substantial decrease of Ps. On the contrary, there was no significant change of
      Ps in bevacizumab treated UM-SCC-22B tumors, compared with control group.
      However, the significant changes of Ps were overestimated in doxorubicin treated
      UM-SCC-22B tumors. Conclusions: We successfully developed a relatively convenient
      and novel strategy to evaluate vascular permeability and blood volume using NEB
      PET. This method will be advantageous in evaluating vascular permeability,
      promoting drug delivery, and monitoring tumor response to therapeutics that
      affect tumor angiogenesis.

PMID- 28744321
TI  - An [18F]-Positron-Emitting, Fluorescent, Cerebrospinal Fluid Probe for Imaging
      Damage to the Brain and Spine.
AB  - Fluorescein is modified to bear 18F so that it can act as both a positron
      emitter, and a fluorophore, allowing detection by positron emission tomography
      (PET), scintillation, and fluorescent imaging (FL). [18F]-2 is injected into the
      intrathecal space of rats and used to observe the cerebrospinal fluid (CSF) that
      bathes the brain and spine. Injury in three different applications is visualized
      with [18F]-2: 1) detection of a 0.7 mm paranasal-sinus CSF leak (CSFL); 2)
      detection of 0.5 mm puncture damage to the thoracic spine (acute spinal cord
      injury); and 3) detection of intracerebral hemorrhage/edema because of traumatic
      brain injury. In all models, the location of injury is visualized with [18F]-2 at
      high resolution. [18F]-2 PET imaging may be a superior alternative to current
      clinical contrast myelography and 131I, 111In or 99mTc radionuclide
      cisternography. Like fluorescein, [18F]-2 may also have other uses in diagnostic
      or fluorescence guided medicine.

PMID- 28744322
TI  - Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9
      Reveals Pre-Metastatic Niche Establishment.
AB  - Background Systemic cancer spread is preceded by the establishment of a
      permissive microenvironment in the target tissue of metastasis - the
      premetastatic niche. As crucial players in establishment of the pre-metastatic
      niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal
      protein that contributes to metastasis, angiogenesis, and immune suppression. We
      report the application of antibody-based single-photon emission computed
      tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for
      pre-metastatic tissue priming. Methods A syngeneic model system for invasive
      breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis
      was established in BALB/c mice. A SPECT-probe has been generated and tested for
      visualization of S100A9 release. Tumor-associated changes in numbers and fuction
      of immune cells in pre-metastatic tissue were evaluated by flow cytometry and
      confocal microscopy. Results S100A8/A9 imaging reflected MDSC abundance and the
      establishment of an immunosuppressive environment in pre-metastatic lung tissue
      (activity 4T1.2 vs. healthy control: 0.95 vs. 0.45 %ID; p<0.001). The S100A8/A9
      imaging signal in the pre-metastatic lung correlated with the subsequent
      metastatic tumor burden in the same organ (r2=0.788; p<0.0001). CCL2 blockade and
      the consecutive inhibition of premetastatic niche establishment was clearly
      depicted by S100A9-SPECT (lung activity untreated vs. treated: 2 vs, 1.4 %ID).
      Conclusion We report S100A8/A9 as a potent imaging biomarker for tumor-mediated
      immune remodeling with potential applications in basic research and clinical
      oncology.

PMID- 28744323
TI  - In-depth Characterization of a TCR-specific Tracer for Sensitive Detection of
      Tumor-directed Transgenic T Cells by Immuno-PET.
AB  - A number of different technologies have been developed to monitor in vivo the
      distribution of gene-modified T cells used in immunotherapy. Nevertheless, in
      depth characterization of novel approaches with respect to sensitivity and
      clinical applicability are so far missing. We have previously described a novel
      method to track engineered human T cells in tumors using 89Zr-Df-aTCRmu-F(ab')2
      targeting the murinized part of the TCR beta domain (TCRmu) of a transgenic TCR.
      Here, we performed an in-depth in vitro characterization of the tracer in terms
      of antigen affinity, immunoreactivity, influence on T-cell functionality and
      stability in vitro and in vivo. Of particular interest, we have developed diverse
      experimental settings to quantify TCR-transgenic T cells in vivo. Local
      application of 89Zr-Df-aTCRmu-F(ab')2-labeled T cells in a spot-assay revealed
      signal detection down to approximately 1.8x104 cells. In a more clinically
      relevant model, NSG mice were intravenously injected with different numbers of
      transgenic T cells, followed by injection of the 89Zr-Df-aTCRmu-F(ab')2 tracer,
      PET/CT imaging and subsequent ex vivo T-cell quantification in the tumor. Using
      this setting, we defined a comparable detection limit of 1.0x104 T cells. PET
      signals correlated well to total numbers of transgenic T cells detected ex vivo
      independently of the engraftment rates observed in different individual
      experiments. Thus, these findings confirm the high sensitivity of our novel
      PET/CT T-cell tracking method and provide critical information about the quantity
      of transgenic T cells in the tumor environment suggesting our technology being
      highly suitable for further clinical translation.

PMID- 28744325
TI  - 3-D Electrochemical Impedance Spectroscopy Mapping of Arteries to Detect
      Metabolically Active but Angiographically Invisible Atherosclerotic Lesions.
AB  - We designed a novel 6-point electrochemical impedance spectroscopy (EIS) sensor
      with 15 combinations of permutations for the 3-D mapping and detection of
      metabolically active atherosclerotic lesions. Two rows of 3 stretchable
      electrodes circumferentially separated by 120 degrees  were mounted on an
      inflatable balloon for intravascular deployment and endoluminal interrogation.
      The configuration and 15 permutations of 2-point EIS electrodes allowed for deep
      arterial penetration via alternating current (AC) to detect varying degrees of
      lipid burden with distinct impedance profiles (Omega). By virtue of the
      distinctive impedimetric signature of metabolically active atherosclerotic
      lesions, a detailed impedance map was acquired, with the 15 EIS permutations
      uncovering early stages of disease characterized by fatty streak lipid
      accumulation in the New Zealand White rabbit model of atherosclerosis. Both the
      equivalent circuit and statistical analyses corroborated the 3-D EIS permutations
      to detect small, angiographically invisible, lipid-rich lesions, with
      translational implications for early atherosclerotic disease detection and
      prevention of acute coronary syndromes or strokes.

PMID- 28744324
TI  - Vibrational Profiling of Brain Tumors and Cells.
AB  - This study reports vibration profiles of neuronal cells and tissues as well as
      brain tumor and neocortical specimens. A contact-free method and analysis
      protocol was designed to convert an atomic force microscope into an ultra
      sensitive microphone with capacity to record and listen to live biological
      samples. A frequency of 3.4 Hz was observed for both cultured rat hippocampal
      neurons and tissues and vibration could be modulated pharmacologically. Malignant
      astrocytoma tissue samples obtained from operating room, transported in
      artificial cerebrospinal fluid, and tested within an hour, vibrated with a much
      different frequency profile and amplitude, compared to meningioma or lateral
      temporal cortex providing a quantifiable measurement to accurately distinguish
      the three tissues in real-time. Vibration signals were converted to audible sound
      waves by frequency modulation, thus demonstrating, acoustic patterns unique to
      meningioma, malignant astrocytoma and neocortex.

PMID- 28744326
TI  - Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine.
AB  - Nitroreductases (NRs) are bacterial enzymes that reduce nitro-containing
      compounds. We have previously reported that NR of intestinal bacteria is a key
      factor promoting berberine (BBR) intestinal absorption. We show here that feeding
      hamsters with high fat diet (HFD) caused an increase in blood lipids and NR
      activity in the intestine. The elevation of fecal NR by HFD was due to the
      increase in either the fraction of NR-producing bacteria or their activity in the
      intestine. When given orally, BBR bioavailability in the HFD-fed hamsters was
      higher than that in those fed with normal chow (by +72%, *P<0.05). BBR (100
      mg/kg/day, orally) decreased blood lipids in the HFD-fed hamsters (**P<0.01) but
      not in those fed with normal diet. Clinical studies indicated that patients with
      hyperlipidemia had higher fecal NR activity than that in the healthy individuals
      (**P<0.01). Similarly, after oral administration, the blood level of BBR in
      hyperlipidemic patients was higher than that in healthy individuals (*P<0.05).
      Correlation analysis revealed a positive relationship between blood BBR and fecal
      NR activity (r=0.703). Thus, the fecal NR activity might serve as a biomarker in
      the personalized treatment of hyperlipidemia using BBR.

PMID- 28744327
TI  - miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide
      Neuroprotection in Huntington's Disease.
AB  - MicroRNAs (miRNAs) play important roles in several neurobiological processes,
      including the development and progression of diseases. Previously, we identified
      that one specific miRNA, miR-196a, provides neuroprotective effects on
      Huntington's disease (HD), although the detailed mechanism is still unclear.
      Based on our bioinformatic analyses, we hypothesize miR-196a might offer
      neuroprotective functions through improving cytoskeletons of brain cells. Here,
      we show that miR-196a could enhance neuronal morphology, further ameliorating
      intracellular transport, synaptic plasticity, neuronal activity, and learning and
      memory abilities. Additionally, we found that miR-196a could suppress the
      expression of RAN binding protein 10 (RANBP10) through binding to its 3'
      untranslated region, and higher expression of RANBP10 exacerbates neuronal
      morphology and intracellular transport. Furthermore, miR-196a enhances neuronal
      morphology through suppressing RANBP10 and increasing the ability of beta-tubulin
      polymerization. Most importantly, we observed higher expression of RANBP10 in the
      brains of HD transgenic mice, and higher expression of RANBP10 might exacerbate
      the pathological aggregates in HD. Taken together, we provide evidence that
      enhancement of neuronal morphology through RANBP10 is one of the neuroprotective
      mechanisms for miR-196a. Since miR-196a has also been reported in other neuronal
      diseases, this study might offer insights with regard to the therapeutic use of
      miR-196a in other neuronal diseases.

PMID- 28744328
TI  - Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon
      Injuries Using Polymer Nanoparticles.
AB  - Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries,
      but it has been challenging to find right diagnosis of minor musculoskeletal
      injuries by conventional ultrasonographic imaging. A large amount of hydrogen
      peroxide (H2O2) are known to be generated during tissue damages such as
      mechanical injury and therefore H2O2 holds great potential as a diagnostic and
      therapeutic marker for mechanical injuries in the musculoskeletal system. We
      previously developed poly(vanillyl alcohol-co-oxalate) (PVAX), which rapidly
      scavenges H2O2 and exerts antioxidant and anti-inflammatory activity in H2O2
      associated diseases. Based on the notion that PVAX nanoparticles generate CO2
      bubbles through H2O2-triggered hydrolysis, we postulated that PVAX nanoparticles
      could serve as ultrasonographic contrast agents and therapeutic agents for
      musculoskeletal injuries associated with overproduction of H2O2. In the agarose
      gel phantom study, PVAX nanoparticles continuously generated CO2 bubbles to
      enhance ultrasonographic echogenicity significantly. Contusion injury
      significantly elevated the level of H2O2 in skeletal muscles and Achilles
      tendons. Upon intramuscular injection, PVAX nanoparticles significantly elevated
      the ultrasound contrast and suppressed inflammation and apoptosis in the
      contusion injury of musculoskeletal systems. We anticipate that PVAX
      nanoparticles hold great translational potential as theranostic agents for
      musculoskeletal injuries.

PMID- 28744329
TI  - PSMA-Targeted Theranostic Nanocarrier for Prostate Cancer.
AB  - Herein, we report the use of a theranostic nanocarrier (Folate-HBPE(CT20p)) to
      deliver a therapeutic peptide to prostate cancer tumors that express PSMA (folate
      hydrolase 1). The therapeutic peptide (CT20p) targets and inhibits the chaperonin
      containing TCP-1 (CCT) protein-folding complex, is selectively cytotoxic to
      cancer cells, and is non-toxic to normal tissue. With the delivery of CT20p to
      prostate cancer cells via PSMA, a dual level of cancer specificity is achieved:
      (1) selective targeting to PSMA-expressing prostate tumors, and (2) specific
      cytotoxicity to cancer cells with minimal toxicity to normal cells. The PSMA
      targeting theranostic nanocarrier can image PSMA-expressing cells and tumors when
      a near infrared dye is used as cargo. Meanwhile, it can be used to treat PSMA
      expressing tumors when a therapeutic, such as the CT20p peptide, is encapsulated
      within the nanocarrier. Even when these PSMA-targeting nanocarriers are taken up
      by macrophages, minimal cell death is observed in these cells, in contrast with
      doxorubicin-based therapeutics that result in significant macrophage death.
      Incubation of PSMA-expressing prostate cancer cells with the Folate-HBPE(CT20p)
      nanocarriers induces considerable changes in cell morphology, reduction in the
      levels of integrin beta1, and lower cell adhesion, eventually resulting in cell
      death. These results are relevant as integrin beta1 plays a key role in prostate
      cancer invasion and metastatic potential. In addition, the use of the developed
      PSMA-targeting nanocarrier facilitates the selective in vivo delivery of CT20p to
      PSMA-positive tumor, inducing significant reduction in tumor size.

PMID- 28744330
TI  - High-Yield Synthesis of Monomeric LMWP(CPP)-siRNA Covalent Conjugate for
      Effective Cytosolic Delivery of siRNA.
AB  - Because of the unparalleled efficiency and universal utility in treating a
      variety of disease types, siRNA agents have evolved as the future drug-of-choice.
      Yet, the inability of the polyanionic siRNA macromolecules to cross the cell
      membrane remains as the bottleneck of possible clinical applications. With the
      cell penetrating peptides (CPP) being discovered lately, the most effective
      tactic to achieve the highest intracellular siRNA delivery deems to be by
      covalently conjugating the drug to a CPP; for instance, the arginine-rich Tat or
      low molecular weight protamine (LMWP) peptides. However, construction of such a
      chemical conjugate has been referred by scientists in this field as the "Holy
      Grail" challenge due to self-assembly of the cationic CPP and anionic siRNA into
      insoluble aggregates that are deprived of the biological functions of both
      compounds. Based on the dynamic motion of PEG, we present herein a concise
      coupling strategy that is capable of permitting a high-yield synthesis of the
      cell-permeable, cytosol-dissociable LMWP-siRNA covalent conjugates. Cell culture
      assessment demonstrates that this chemical conjugate yields by far the most
      effective intracellular siRNA delivery and its corresponded gene-silencing
      activities. This work may offer a breakthrough advance towards realizing the
      clinical potential of all siRNA therapeutics and, presumably, most anionic
      macromolecular drugs such as anti-sense oligonucleotides, gene compounds, DNA
      vectors and proteins where conjugation with the CPP encounters with problems of
      aggregation and precipitation. To this end, the impact of this coupling technique
      is significant, far-reaching and wide-spread.

PMID- 28744331
TI  - Fabrication of Tissue-Engineered Bionic Urethra Using Cell Sheet Technology and
      Labeling By Ultrasmall Superparamagnetic Iron Oxide for Full-Thickness Urethral
      Reconstruction.
AB  - Urethral strictures remain a reconstructive challenge, due to less than
      satisfactory outcomes and high incidence of stricture recurrence. An "ideal"
      urethral reconstruction should establish similar architecture and function as the
      original urethral wall. We fabricated a novel tissue-engineered bionic urethras
      using cell sheet technology and report their viability in a canine model. Small
      amounts of oral and adipose tissues were harvested, and adipose-derived stem
      cells, oral mucosal epithelial cells, and oral mucosal fibroblasts were isolated
      and used to prepare cell sheets. The cell sheets were hierarchically tubularized
      to form 3-layer tissue-engineered urethras and labeled by ultrasmall super
      paramagnetic iron oxide (USPIO). The constructed tissue-engineered urethras were
      transplanted subcutaneously for 3 weeks to promote the revascularization and
      biomechanical strength of the implant. Then, 2 cm length of the tubularized
      penile urethra was replaced by tissue-engineered bionic urethra. At 3 months of
      urethral replacement, USPIO-labeled tissue-engineered bionic urethra can be
      effectively detected by MRI at the transplant site. Histologically, the retrieved
      bionic urethras still displayed 3 layers, including an epithelial layer, a
      fibrous layer, and a myoblast layer. Three weeks after subcutaneous
      transplantation, immunofluorescence analysis showed the density of blood vessels
      in bionic urethra was significantly increased following the initial establishment
      of the constructs and was further up-regulated at 3 months after urethral
      replacement and was close to normal level in urethral tissue. Our study is the
      first to experimentally demonstrate 3-layer tissue-engineered urethras can be
      established using cell sheet technology and can promote the regeneration of
      structural and functional urethras similar to normal urethra.

PMID- 28744332
TI  - Rapid In Situ MRI Traceable Gel-forming Dual-drug Delivery for Synergistic
      Therapy of Brain Tumor.
AB  - Preventing tumor recurrence after surgical resection of a brain tumor is a
      significant clinical challenge because current methods deliver chemotherapeutic
      agents in a rapid manner and are not effective against the residual tumor cells.
      To overcome this drawback, we report a simple method to prepare magnetic
      resonance imaging (MRI) traceable ultra-thermosensitive hydrogels with rapid
      gelation ability from aqueous solution within 4 s at 28  degrees C for
      hydrophilic (epirubicin, EPI) and hydrophobic (paclitaxel, PTX) drugs co-delivery
      with bovine serum albumin nanoparticles (BSA NPs) incorporation. The results
      showed the average survival of gliosarcoma-bearing (MBR 614 or U87) mice
      receiving BSA/PTX NPs incorporated hydrogelGd/EPI increased to 63 days or 69 days
      with no tumor recurrence observed. Our synergistic strategy presents a new
      approach to the development of a local drug delivery system for the prevention of
      brain tumor recurrence.

PMID- 28744333
TI  - Regulation on Toll-like Receptor 4 and Cell Barrier Function by Rab26 siRNA
      loaded DNA Nanovector in Pulmonary Microvascular Endothelial Cells.
AB  - The small GTPase Rab26 is involved in multiple processes, such as vesicle
      mediated secretion and autophagy. However, the mechanisms and functions of Rab26
      in the human pulmonary microvascular endothelial cells (HPMVECs) are not clear.
      In this study, we thoroughly investigated the role and novel mechanism of Rab26
      in permeability and apoptosis of HPMVECs using a self-assembled Rab26 siRNA
      loaded DNA Y-motif nanoparticle (siRab26-DYM) and Rab26 adenovirus. We found that
      siRab26-DYM could be efficiently transfected into HPMVECs in a time- and dose
      dependent manner. Importantly, the siRab26-DYM nanovector markedly aggravated the
      LPS-induced apoptosis and hyper-permeability of HPMVECs by promoting the nuclear
      translocation of Foxo1, and subsequent activation of Toll-like receptor 4 (TLR4)
      signal pathway. Overexpression of Rab26 by Rab26 adenoviruses partially
      inactivated LPS-induced TLR4 signaling pathway, suppressed the cell apoptosis and
      attenuated the hyperpermeability of HPMVECs. These results suggest that the
      permeability and apoptosis of HPMVECs can be modulated by manipulating Rab26
      derived TLR4 signaling pathway, and that Rab26 can be potential therapeutic
      target for the treatment of vascular diseases related to endothelial barrier
      functions.

PMID- 28744334
TI  - Robotic Surgical System for Radical Prostatectomy: A Health Technology
      Assessment.
AB  - BACKGROUND: Prostate cancer is the second most common type of cancer in Canadian
      men. Radical prostatectomy is one of the treatment options available, and
      involves removing the prostate gland and surrounding tissues. In recent years,
      surgeons have begun to use robot-assisted radical prostatectomy more frequently.
      We aimed to determine the clinical benefits and harms of the robotic surgical
      system for radical prostatectomy (robot-assisted radical prostatectomy) compared
      with the open and laparoscopic surgical methods. We also assessed the cost
      effectiveness of robot-assisted versus open radical prostatectomy in patients
      with clinically localized prostate cancer in Ontario. METHODS: We performed a
      literature search and included prospective comparative studies that examined
      robot-assisted versus open or laparoscopic radical prostatectomy for prostate
      cancer. The outcomes of interest were perioperative, functional, and oncological.
      The quality of the body of evidence was examined according to the Grading of
      Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group
      criteria. We also conducted a cost-utility analysis with a 1-year time horizon.
      The potential long-term benefits of robot-assisted radical prostatectomy for
      functional and oncological outcomes were also evaluated in a 10-year Markov model
      in scenario analyses. In addition, we conducted a budget impact analysis to
      estimate the additional costs to the provincial budget if the adoption of robot
      assisted radical prostatectomy were to increase in the next 5 years. A needs
      assessment determined that the published literature on patient perspectives was
      relatively well developed, and that direct patient engagement would add
      relatively little new information. RESULTS: Compared with the open approach, we
      found robot-assisted radical prostatectomy reduced length of stay and blood loss
      (moderate quality evidence) but had no difference or inconclusive results for
      functional and oncological outcomes (low to moderate quality evidence). Compared
      with laparoscopic radical prostatectomy, robot-assisted radical prostatectomy had
      no difference in perioperative, functional, and oncological outcomes (low to
      moderate quality evidence). Compared with open radical prostatectomy, our best
      estimates suggested that robot-assisted prostatectomy was associated with higher
      costs ($6,234) and a small gain in quality-adjusted life-years (QALYs) (0.0012).
      The best estimate of the incremental cost-effectiveness ratio (ICER) was $5.2
      million per QALY gained. However, if robot-assisted radical prostatectomy were
      assumed to have substantially better long-term functional and oncological
      outcomes, the ICER might be as low as $83,921 per QALY gained. We estimated the
      annual budget impact to be $0.8 million to $3.4 million over the next 5 years.
      CONCLUSIONS: There is no high-quality evidence that robot-assisted radical
      prostatectomy improves functional and oncological outcomes compared with open and
      laparoscopic approaches. However, compared with open radical prostatectomy, the
      costs of using the robotic system are relatively large while the health benefits
      are relatively small.

PMID- 28744335
TI  - Left Atrial Appendage Closure Device With Delivery System: A Health Technology
      Assessment.
AB  - BACKGROUND: Atrial fibrillation is a common cardiac arrhythmia, and 15% to 20% of
      those who have experienced stroke have atrial fibrillation. Treatment options to
      prevent stroke in people with atrial fibrillation include pharmacological agents
      such as novel oral anticoagulants or nonpharmacological devices such as the left
      atrial appendage closure device with delivery system (LAAC device). The
      objectives of this health technology assessment were to assess the clinical
      effectiveness and cost-effectiveness of the LAAC device versus novel oral
      anticoagulants in patients without contraindications to oral anticoagulants and
      versus antiplatelet agents in patients with contraindications to oral
      anticoagulants. METHODS: We performed a systematic review and network meta
      analysis. We also conducted an economic literature review, economic evaluation,
      and budget impact analysis to assess the cost-effectiveness and budget impact of
      the LAAC device compared with novel oral anticoagulants and oral antiplatelet
      agents (e.g., aspirin). We also spoke with patients to better understand their
      preferences, perspectives, and values. RESULTS: Seven randomized controlled
      studies met the inclusion criteria for indirect comparison. Five studies assessed
      the effectiveness of novel oral anticoagulants versus warfarin, and two studies
      compared the LAAC device with warfarin. No studies were identified that compared
      the LAAC device with aspirin in patients in whom oral anticoagulants were
      contraindicated. Using the random effects model, we found that the LAAC device
      was comparable to novel oral anticoagulants in reducing stroke (odds ratio [OR]
      0.85; credible interval [Cr.I] 0.63-1.05). Similarly, the reduction in the risk
      of all-cause mortality was comparable between the LAAC device and novel oral
      anticoagulants (OR 0.71; Cr.I 0.49-1.22). The LAAC device was found to be
      superior to novel oral anticoagulants in preventing hemorrhagic stroke (OR 0.45;
      Cr.I 0.29-0.79), whereas novel oral anticoagulants were found to be superior to
      the LAAC device in preventing ischemic stroke (OR 0.67; Cr.I 0.24-1.64). The body
      of clinical evidence was found to be of moderate quality as assed by the Grading
      of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group
      criteria. Results from the economic evaluation indicate that the LAAC device is
      cost-effective compared with aspirin in patients with contraindications to oral
      anticoagulants. In patients without contraindications to oral anticoagulants, we
      found that the LAAC device is not cost-effective compared with novel oral
      anticoagulants. Publicly funding the LAAC device in patients with nonvalvular
      atrial fibrillation with contraindications to oral anticoagulants could result in
      additional funding of $1.1 million to $7.7 million over the first five years.
      Patients interviewed reported on the impact of living with nonvalvular atrial
      fibrillation and were supportive of the LAAC device as a treatment option.
      CONCLUSIONS: Moderate-quality evidence suggests that the LAAC device is as
      effective as novel oral anticoagulants in preventing stroke in people with
      nonvalvular atrial fibrillation. However, our results indicate that the LAAC
      device is cost-effective only in patients with contraindications to oral
      anticoagulants. People with nonvalvular atrial fibrillation with whom we spoke
      reported positive support for the LAAC device.

PMID- 28744336
TI  - Oxidative Phosphorylation System in Gastric Carcinomas and Gastritis.
AB  - Switching of cellular energy production from oxidative phosphorylation (OXPHOS)
      by mitochondria to aerobic glycolysis occurs in many types of tumors. However,
      the significance of this switching for the development of gastric carcinoma and
      what connection it may have to Helicobacter pylori infection of the gut, a
      primary cause of gastric cancer, are poorly understood. Therefore, we
      investigated the expression of OXPHOS complexes in two types of human gastric
      carcinomas ("intestinal" and "diffuse"), bacterial gastritis with and without
      metaplasia, and chemically induced gastritis by using immunohistochemistry.
      Furthermore, we analyzed the effect of HP infection on several key mitochondrial
      proteins. Complex I expression was significantly reduced in intestinal type (but
      not diffuse) gastric carcinomas compared to adjacent control tissue, and the
      reduction was independent of HP infection. Significantly, higher complex I and
      complex II expression was present in large tumors. Furthermore, higher complex II
      and complex III protein levels were also obvious in grade 3 versus grade 2. No
      differences of OXPHOS complexes and markers of mitochondrial biogenesis were
      found between bacterially caused and chemically induced gastritis. Thus,
      intestinal gastric carcinomas, but not precancerous stages, are frequently
      characterized by loss of complex I, and this pathophysiology occurs independently
      of HP infection.

PMID- 28744337
TI  - Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential
      Antioxidant Therapies.
AB  - Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease whose
      incidence has risen worldwide in recent years. Accumulating evidence shows that
      oxidative stress plays an essential role in the pathogenesis and progression of
      IBD. This review highlights the generation of reactive oxygen species (ROS) and
      antioxidant defense mechanisms in the gastrointestinal (GI) tract, the
      involvement of oxidative stress signaling in the initiation and progression of
      IBD and its relationships with genetic susceptibility and the mucosal immune
      response. In addition, potential therapeutic strategies for IBD that target
      oxidative stress signaling are reviewed and discussed. Though substantial
      progress has been made in understanding the role of oxidative stress in IBD in
      humans and experimental animals, the underlying mechanisms are still not well
      defined. Thus, further studies are needed to validate how oxidative stress
      signaling is involved in and contributes to the development of IBD.

PMID- 28744339
TI  - Effect of Cocoa Polyphenolic Extract on Macrophage Polarization from
      Proinflammatory M1 to Anti-Inflammatory M2 State.
AB  - Polyphenols-rich cocoa has many beneficial effects on human health, such as anti
      inflammatory effects. Macrophages function as control switches of the immune
      system, maintaining the balance between pro- and anti-inflammatory activities. We
      investigated the hypothesis that cocoa polyphenol extract may affect macrophage
      proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory
      state on macrophages deriving from THP-1 cells. Chemical composition, total
      phenolic content, and antioxidant capacity of cocoa polyphenols extracted from
      roasted cocoa beans were determined. THP-1 cells were activated with both
      lipopolysaccharides and interferon-gamma for M1 or with IL-4 for M2 switch, and
      specific cytokines were quantified. Cellular metabolism, through mitochondrial
      oxygen consumption, and ATP levels were evaluated. Here, we will show that cocoa
      polyphenolic extract attenuated in vitro inflammation decreasing M1 macrophage
      response as demonstrated by a significantly lowered secretion of proinflammatory
      cytokines. Moreover, treatment of M1 macrophages with cocoa polyphenols
      influences macrophage metabolism by promoting oxidative pathways, thus leading to
      a significant increase in O2 consumption by mitochondrial complexes as well as a
      higher production of ATP through oxidative phosphorylation. In conclusion, cocoa
      polyphenolic extract suppresses inflammation mediated by M1 phenotype and
      influences macrophage metabolism by promoting oxidative pathways and M2
      polarization of active macrophages.

PMID- 28744338
TI  - Role of Kallistatin Treatment in Aging and Cancer by Modulating miR-34a and miR
      21 Expression.
AB  - Kallistatin is an endogenous protein that regulates differential signaling
      pathways and a wide spectrum of biological activities via its two structural
      elements: an active site and a heparin-binding domain. Kallistatin via its
      heparin-binding site inhibits vascular inflammation and oxidative stress by
      antagonizing TNF-alpha-induced NADPH oxidase activity, NF-kappaB activation, and
      inflammatory gene expression in endothelial cells. Moreover, kallistatin via its
      active site inhibits microRNA-34a (miR-34a) synthesis and stimulates eNOS and
      SIRT1 expression in endothelial progenitor cells, whereas its heparin-binding
      site is crucial for blocking TNF-alpha-induced miR-21 expression and oxidative
      stress, thus reducing cellular senescence. By downregulating miR-34a and miR-21
      expression, kallistatin treatment attenuates oxidative damage and aortic
      senescence in streptozotocin-induced diabetic mice and extends Caenorhabditis
      elegans lifespan under stress conditions. Likewise, kallistatin through the
      heparin-binding site inhibits TGF-beta-induced miR-21 synthesis and oxidative
      stress in endothelial cells, resulting in inhibition of endothelial-mesenchymal
      transition, a process contributing to fibrosis and cancer. Furthermore,
      kallistatin's active site is essential for stimulating miR-34a and p53 expression
      and inhibiting the miR-21-Akt-Bcl-2 signaling pathway, thus inducing apoptosis in
      breast cancer cells. These findings reveal novel mechanisms of kallistatin in
      protection against senescence, aging, and cancer development by modulating miR
      34a and miR-21 levels and inhibiting oxidative stress.

PMID- 28744341
TI  - Assessment of the July effect in post-endoscopic retrograde
      cholangiopancreatography pancreatitis: Nationwide Inpatient Sample.
AB  - AIM: To assess incidence of post-endoscopic retrograde cholangiopancreatography
      (post-ERCP) pancreatitis in the early (July/August/September) vs the late
      (April/May/June) academic year and evaluate in-hospital mortality, length of stay
      (LOS), and total hospitalization charge between these time periods. METHODS: This
      was a retrospective cohort study using the 2012 Nationwide Inpatient Sample
      (NIS). Patients with International Classification of Diseases, 9th Revision,
      Clinical Modification (ICD-9 CM) procedure codes for ERCP were included. Patients
      were excluded from the study if they had an ICD-9 CM code for a principal
      diagnosis of acute pancreatitis, if the ERCP was performed before or on the day
      of admission or if they were admitted to non-teaching hospitals. Post-ERCP
      pancreatitis was defined as an ICD-9 CM code for a secondary diagnosis of acute
      pancreatitis in patients who received an ERCP as delineated above. ERCPs
      performed during the months of July, August and September was compared to those
      performed in April, May and June in academic hospitals. ERCPs performed at
      academic hospitals during the early vs late year were compared. Primary outcome
      was incidence of post-ERCP pancreatitis. Secondary outcomes included in-hospital
      mortality, length of stay (LOS), and total hospitalization charge. Proportions
      were compared using fisher's exact test and continuous variables using student t
      test. Multivariable regression was performed. RESULTS: From the 36480032
      hospitalizations in 2012 in the United States, 6248 were included in the study
      (3065 in July/August/September and 3183 in April/May/June) in the 2012 academic
      year. Compared with patients admitted in July/August/September, patients admitted
      in April/May/June had no statistical difference in all variables including mean
      age, percent female, Charleston comorbidity index, race, median income, and
      hospital characteristics including region, bed size, and location. Incidence of
      post-ERCP pancreatitis in early vs late academic year were not statistically
      significant (OR = 1.03, 95%CI: 0.71-1.51, P = 0.415). Similarly, the adjusted
      odds ratio of mortality, LOS, and total hospitalization charge in early compared
      to late academic year were not statistically significant. CONCLUSION: Incidence
      of post-ERCP pancreatitis does not differ at academic institutions depending on
      the time of year. Similarly, mortality, LOS, and total hospital charge do not
      demonstrate the existence of a temporal effect, suggesting that trainee level of
      experience does not impact clinical outcomes in patients undergoing ERCP.

PMID- 28744340
TI  - Commiphora molmol Modulates Glutamate-Nitric Oxide-cGMP and Nrf2/ARE/HO-1
      Pathways and Attenuates Oxidative Stress and Hematological Alterations in
      Hyperammonemic Rats.
AB  - Hyperammonemia is a serious complication of liver disease and may lead to
      encephalopathy and death. This study investigated the effects of Commiphora
      molmol resin on oxidative stress, inflammation, and hematological alterations in
      ammonium chloride- (NH4Cl-) induced hyperammonemic rats, with an emphasis on the
      glutamate-NO-cGMP and Nrf2/ARE/HO-1 signaling pathways. Rats received NH4Cl and
      C. molmol for 8 weeks. NH4Cl-induced rats showed significant increase in blood
      ammonia, liver function markers, and tumor necrosis factor-alpha (TNF-alpha).
      Concurrent supplementation of C. molmol significantly decreased circulating
      ammonia, liver function markers, and TNF-alpha in hyperammonemic rats. C. molmol
      suppressed lipid peroxidation and nitric oxide and enhanced the antioxidant
      defenses in the liver, kidney, and cerebrum of hyperammonemic rats. C. molmol
      significantly upregulated Nrf2 and HO-1 and decreased glutamine and nitric oxide
      synthase, soluble guanylate cyclase, and Na+/K+-ATPase expression in the cerebrum
      of NH4Cl-induced hyperammonemic rats. Hyperammonemia was also associated with
      hematological and coagulation system alterations. These alterations were reversed
      by C. molmol. Our findings demonstrated that C. molmol attenuates ammonia-induced
      liver injury, oxidative stress, inflammation, and hematological alterations. This
      study points to the modulatory effect of C. molmol on glutamate-NO-cGMP and
      Nrf2/ARE/HO-1 pathways in hyperammonemia. Therefore, C. molmol might be a
      promising protective agent against hyperammonemia.

PMID- 28744342
TI  - Efficacy of a newly developed dilator for endoscopic ultrasound-guided biliary
      drainage.
AB  - AIM: To evaluate the efficacy of a newly developed dilator for endoscopic
      ultrasound (EUS)-guided drainage (ES Dilator). METHODS: Fourteen consecutive
      patients who had undergone EUS-guided choledochoduodenostomy (EUS-CDS) with the
      ES Dilator were identified from a prospectively maintained database and enrolled
      in the study group. Fourteen other patients who had undergone EUS-CDS without the
      dilator just prior to its introduction were analyzed as the control group. A
      historical cohort study was carried out comparing the two groups. The main
      outcome measurement was the procedure time. The technical success rate and early
      AE rate were also compared between the two groups. RESULTS: There were no
      significant differences in age, sex and etiology of biliary obstruction. The
      utilization rate of a plastic stent was higher in the control group (36% vs 0%).
      The technical success rate was 100% in both groups. The mean procedure time was
      significantly shorter in the study group than in the control group (27 +/- 7 min
      vs 44 +/- 26 min, P = 0.026). Additionally, there were no patients who required
      more than 40 min for the procedure in the study group. Early adverse events
      occurred in 29% (4/14) of the control group whereas none in the study group. The
      adverse events in all 4 patients was bile peritonitis, including pan-peritonitis
      in one patient. All patients recovered with conservative treatment by medication.
      CONCLUSION: The newly developed dilator was found to be useful for shortening
      procedure time and would prevent adverse events related to bile leakage in EUS
      CDS.

PMID- 28744343
TI  - Use of shape-from-shading to characterize mucosal topography in celiac disease
      videocapsule images.
AB  - AIM: To use a computerized shape-from-shading technique to characterize the
      topography of the small intestinal mucosa. METHODS: Videoclips comprised of 100
      200 images each were obtained from the distal duodenum in 8 celiac and 8 control
      patients. Images with high texture were selected from each videoclip and
      projected from two to three dimensions by using grayscale pixel brightness as the
      Z-axis spatial variable. The resulting images for celiac patients were then
      ordered using the Marsh score to estimate the degree of villous atrophy, and
      compared with control data. RESULTS: Topographic changes in celiac patient three
      dimensional constructs were often more variable as compared to controls. The mean
      absolute derivative in elevation was 2.34 +/- 0.35 brightness units for celiacs
      vs 1.95 +/- 0.28 for controls (P = 0.014). The standard deviation of the
      derivative in elevation was 4.87 +/- 0.35 brightness units for celiacs vs 4.47 +/
      0.36 for controls (P = 0.023). Celiac patients with Marsh IIIC villous atrophy
      tended to have the largest topographic changes. Plotted in two dimensions, celiac
      data could be separated from controls with 80% sensitivity and specificity.
      CONCLUSION: Use of shape-from-shading to construct three-dimensional projections
      approximating the actual spatial geometry of the small intestinal substrate is
      useful to observe features not readily apparent in two-dimensional videocapsule
      images. This method represents a potentially helpful adjunct to detect areas of
      pathology during videocapsule analysis.

PMID- 28744344
TI  - Use of volumetric laser endomicroscopy for dysplasia detection at the
      gastroesophageal junction and gastric cardia.
AB  - AIM: To determine specific volumetric laser endomicroscopy (VLE) imaging features
      associated with neoplasia at the gastroesophageal junction (GEJ) and gastric
      cardia. METHODS: During esophagogastroduodenoscopy for patients with known or
      suspected Barrett's esophagus, VLE was performed before biopsies were taken at
      endoscopists' discretion. The gastric cardia was examined on VLE scan from the
      GEJ (marked by top of gastric folds) to 1 cm distal from the GEJ. The NinePoints
      VLE console was used to analyze scan segments for characteristics previously
      found to correlate with normal or abnormal mucosa. Glands were counted
      individually. Imaging features identified on VLE scan were correlated with biopsy
      results from the GEJ and cardia region. RESULTS: This study included 34 cases.
      Features characteristic of the gastric cardia (gastric rugae, gastric pit
      architecture, poor penetration) were observed in all (100%) scans. Loss of
      classic gastric pit architecture was common and there was no difference between
      those with neoplasia and without (100% vs 74%, P = NS). The abnormal VLE feature
      of irregular surface was more often seen in patients with neoplasia than those
      without (100% vs 18%, P < 0.0001), as was heterogeneous scattering (86% vs 41%, P
      < 0.005) and presence of anomalous glands (100% vs 59%, P < 0.05). The number of
      anomalous glands did not differ between individual histologic subgroups (ANOVA, P
      = NS). CONCLUSION: The transition from esophagus to gastric cardia is reliably
      identified on VLE. Histologically abnormal cardia mucosa produces abnormal VLE
      features. Optical coherence tomography algorithms can be expanded for use at the
      GEJ/cardia.

PMID- 28744345
TI  - All ileo-cecal ulcers are not Crohn's: Changing perspectives of symptomatic
      ileocecal ulcers.
AB  - AIM: To investigated clinical, endoscopic and histopathological parameters of the
      patients presenting with ileocecal ulcers on colonoscopy. METHODS: Consecutive
      symptomatic patients undergoing colonoscopy, and diagnosed to have ulcerations in
      the ileocecal (I/C) region, were enrolled. Biopsy was obtained and their clinical
      presentation and outcome were recorded. RESULTS: Out of 1632 colonoscopies, 104
      patients had ulcerations in the I/C region and were included in the study. Their
      median age was 44.5 years and 59% were males. The predominant presentation was
      lower GI bleed (55, 53%), pain abdomen +/- diarrhea (36, 35%), fever (32, 31%),
      and diarrhea alone (9, 9%). On colonoscopy, terminal ileum was entered in 96
      (92%) cases. The distribution of ulcers was as follows: Ileum alone 40% (38/96),
      cecum alone 33% (32/96), and both ileum plus cecum 27% (26/96). The ulcers were
      multiple in 98% and in 34% there were additional ulcers elsewhere in colon. Based
      on clinical presentation and investigations, the etiology of ulcers was
      classified into infective causes (43%) and non-infective causes (57%). Fourteen
      patients (13%) were diagnosed to have Crohn's disease (CD). CONCLUSION: Non
      specific ileocecal ulcers are most common ulcers seen in ileo-cecal region. And
      if all infections are clubbed together then infection is the most common (> 40%)
      cause of ulcerations of the I/C region. Cecal involvement and fever are important
      clues to infective cause. On the contrary CD account for only 13% cases as a
      cause of ileo-cecalulcers. So all symptomatic patients with I/C ulcers on
      colonoscopy are not Crohn's.

PMID- 28744346
TI  - Endoscopic submucosal dissection of gastric adenomas using the clutch cutter.
AB  - AIM: To evaluate the efficacy and safety of endoscopic submucosal dissection
      (ESD) using the clutch cutter (CC) (ESD-CC) for gastric adenoma (GA). METHODS:
      From June 2007 to August 2015, 122 consecutive patients with histological
      diagnoses of GA from specimens resected by ESD-CC were enrolled in this
      prospective study. The CC was used for all ESD steps (marking, mucosal incision,
      submucosal dissection, and hemostatic treatment), and its therapeutic efficacy
      and safety were assessed. RESULTS: Both the en-bloc resection rate and the R0
      resection rate were 100% (122/122). The mean surgical time was 77.4 min, but the
      time varied significantly according to tumor size and location. No patients
      suffered perforation. Post-ESD-CC bleeding occurred in six cases (4.9%) that were
      successfully resolved by endoscopic hemostatic treatment. CONCLUSION: ESD-CC is a
      technically efficient, safe, and easy method for resecting GA.

PMID- 28744347
TI  - Management of hyperplastic gastric polyp following upper gastrointestinal
      bleeding in infant with Menkes' disease.
AB  - We report a case of an infant with Menkes' disease (MD) presented at the age of
      five months, with coffee ground vomiting, melaena with a significant drop of
      haemoglobin. Urgent endoscopic assessment revealed a friable bleeding trans
      pyloric multi-lobulated sessile polyp. Due to further significant upper
      gastrointestinal bleeding, polypectomy occurred. Endoscopic mucosal resection was
      performed with a grasp-and-snare technique using a dual channel operating
      gastroscope. Haemostasis was achieved by application of argon plasma coagulation
      where required. No perforation occurred. Repeated debridement was required 6 wk
      after which the growth was excised completely with no further blood transfusion
      required after that procedure. Histological examination confirmed ulcerated and
      inflamed hyperplastic polyp. We discuss our endoscopic technique and discuss the
      reported gastrointestinal manifestation of MD in the literature.

PMID- 28744348
TI  - In Silico Prediction of Organ Level Toxicity: Linking Chemistry to Adverse
      Effects.
AB  - In silico methods to predict toxicity include the use of (Quantitative) Structure
      Activity Relationships ((Q)SARs) as well as grouping (category formation)
      allowing for read-across. A challenging area for in silico modelling is the
      prediction of chronic toxicity and the No Observed (Adverse) Effect Level
      (NO(A)EL) in particular. A proposed solution to the prediction of chronic
      toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL
      itself. This review has focussed on the use of structural alerts to identify
      potential liver toxicants. In silico profilers, or groups of structural alerts,
      have been developed based on mechanisms of action and informed by current
      knowledge of Adverse Outcome Pathways. These profilers are robust and can be
      coded computationally to allow for prediction. However, they do not cover all
      mechanisms or modes of liver toxicity and recommendations for the improvement of
      these approaches are given.

PMID- 28744349
TI  - AAALAC International Standards and Accreditation Process.
AB  - AAALAC International is a private, nonprofit organization that promotes humane
      treatment of animals in science through a voluntary international accreditation
      program. AAALAC International accreditation is recognized around the world as a
      symbol of high quality animal care and use for research, teaching and testing, as
      well as promoting animal welfare. Animals owned by the institution that are used
      for research, teaching and testing are included as part of an accredited program.
      More than 990 animal care and use institutions in 42 countries around the world
      (more than 170 programs in 13 countries in the Pacific Rim region) have earned
      AAALAC International accreditation. The AAALAC International Council on
      Accreditation evaluates overall performance and all aspects of an animal care and
      use program, involving an in-depth, multilayered, confidential peer-review
      process. The evaluators (site visitors) consider compliance with applicable local
      animal legislation of the host country, institutional policies, and employ a
      customized approach for evaluating overall program performance using a series of
      primary standards that include the Guide for the Care and Use of Laboratory
      Animals, the Guide for the Care and Use of Agricultural Animals in Research and
      Teaching, or the European Convention for the Protection of Vertebrate Animals
      Used for Experimental and Other Purposes, Council of Europe (ETS 123), and
      supplemental Reference Resources, as applicable.

PMID- 28744350
TI  - Alternatives to In Vivo Draize Rabbit Eye and Skin Irritation Tests with a Focus
      on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models.
AB  - Human eyes and skin are frequently exposed to chemicals accidentally or on
      purpose due to their external location. Therefore, chemicals are required to
      undergo the evaluation of the ocular and dermal irritancy for their safe handling
      and use before release into the market. Draize rabbit eye and skin irritation
      test developed in 1944, has been a gold standard test which was enlisted as OECD
      TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare
      due to invasive and cruel procedure. To replace it, diverse alternatives have
      been developed: (i) For Draize eye irritation test, organotypic assay, in vitro
      cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D
      reconstructed human cornea-like epithelium (RhCE); (ii) For Draize skin
      irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed
      human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight
      as a promising alternative with a wide applicability domain covering cosmetics
      and personal care products. In this review, we overviewed the current
      alternatives to Draize test with a focus on 3D human epithelium models to provide
      an insight into advancing and widening their utility.

PMID- 28744351
TI  - TMEM39A and Human Diseases: A Brief Review.
AB  - Transmembrane Protein 39A (TMEM39A) is a member of TMEM family. The understanding
      about this protein is still limited. The earlier studies indicated that TMEM39A
      was a key mediator of autoimmune disease. TMEM39A seems to be involved in
      systemic lupus erythematosus and multiple sclerosis in numerous of populations.
      All of these works stop at insufficient information by using gene functioning
      methods such as: Genome-wide association studies (GWASs) and/or follow-up study.
      It is the fact that the less understood of TMEM39A actually is the attraction to
      the scientist in near future. In this review the current knowledge about TMEM39A
      and its possible roles in cell biology, physiology and pathology will be
      described.

PMID- 28744352
TI  - CYP1B1 Activates Wnt/beta-Catenin Signaling through Suppression of Herc5-Mediated
      ISGylation for Protein Degradation on beta-Catenin in HeLa Cells.
AB  - Cytochrome P450 1B1 (CYP1B1) acts as a hydroxylase for estrogen and activates
      potential carcinogens. Moreover, its expression in tumor tissues is much higher
      than that in normal tissues. Despite this association between CYP1B1 and cancer,
      the detailed molecular mechanism of CYP1B1 on cancer progression in HeLa cells
      remains unknown. Previous reports indicated that the mRNA expression level of
      Herc5, an E3 ligase for ISGylation, is promoted by CYP1B1 suppression using
      specific small interfering RNA, and that ISGylation may be involved in
      ubiquitination related to beta-catenin degradation. With this background, we
      investigated the relationships among CYP1B1, Herc5, and beta-catenin. RT-PCR and
      western blot analyses showed that CYP1B1 overexpression induced and CYP1B1
      inhibition reduced, respectively, the expression of Wnt/beta-catenin signaling
      target genes including beta-catenin and cyclin D1. Moreover, HeLa cells were
      treated with the CYP1B1 inducer 7,12-dimethylbenz[alpha]anthracene (DMBA) or the
      CYP1B1 specific inhibitor, tetramethoxystilbene (TMS) and consequently DMBA
      increased and TMS decreased beta-catenin and cyclin D1 expression, respectively.
      To determine the correlation between CYP1B1 expression and ISGylation, the
      expression of ISG15, a ubiquitin-like protein, was detected following CYP1B1
      regulation, which revealed that CYP1B1 may inhibit ISGylation through suppression
      of ISG15 expression. In addition, the mRNA and protein expression levels of Herc5
      were strongly suppressed by CYP1B1. Finally, an immunoprecipitation assay
      revealed a direct physical interaction between Herc5 and beta-catenin in HeLa
      cells. In conclusion, these data suggest that CYP1B1 may activate Wnt/beta
      catenin signaling through stabilization of beta-catenin protein from Herc5
      mediated ISGylation for proteosomal degradation.

PMID- 28744353
TI  - Induction of Lipin1 by ROS-Dependent SREBP-2 Activation.
AB  - Lipin1 was identified as a phosphatidate phosphatase enzyme, and it plays a key
      role in lipid metabolism. Since free radicals contribute to metabolic diseases in
      the liver, this study investigated the effects of free radicals on the regulation
      of Lipin1 expression in Huh7 and AML12 cells. Hydrogen peroxide induced mRNA and
      protein expression of Lipin1 in Huh7 cells, which was assayed by quantitative RT
      PCR and immunoblotting, respectively. Induction of Lipin1 by hydrogen peroxide
      was confirmed in AML12 cells. Hydrogen peroxide treatment significantly increased
      expression of sterol regulatory element-binding protein (SREBP)-2, but not SREBP
      1. Moreover, nuclear translocation of SREBP-2 was detected after hydrogen
      peroxide treatment. Hydrogen peroxide-induced Lipin1 or SREBP-2 expression was
      significantly reduced by N-acetyl-l-cysteine treatment, indicating that reactive
      oxygen species (ROS) were implicated in Lipin1 expression. Next, we investigated
      whether the hypoxic environments that cause endogenous ROS production in
      mitochondria in metabolic diseases affect the expression of Lipin1. Exposure to
      hypoxia also increased Lipin1 expression. In contrast, pretreatment with
      antioxidants attenuated hypoxia-induced Lipin1 expression. Collectively, our
      results show that ROS activate SREBP-2, which induces Lipin1 expression.

PMID- 28744354
TI  - Stability Evaluation of National Reference Standards for Blood Products in Korea.
AB  - National reference standards (NRSs) for biologics are established through potency
      estimation by a multicenter joint study of standard materials used in the
      approval process for national lot release and quality control of vaccines, blood
      products, and other biologics. In this study, a stability evaluation was
      conducted to determine whether the potency of NRSs for six blood products was
      being maintained at a consistent level in Korea. The present study conducted real
      time stability tests via in-vivo/in-vitro bioassay on NRSs for blood coagulation
      factor VIII concentrate (2nd standard), antithrombin concentrate, prekallikrein
      activator, anti-hepatitis B immunoglobulin, blood coagulation factor IX
      concentrate, and anti-tetanus human immunoglobulin, as well as a trend analysis
      using cumulative annual results. The real-time stability test results showed that
      the mean potency of six NRSs was all within the control limit. In the trend
      analysis, the potency of NRS for blood coagulation factor VIII concentrate (2nd
      standard) showed a decreasing trend, while the potency of all other products had
      been stably maintained. The present study confirmed that the mean potency of NRSs
      for six blood products had been stably maintained in Korea. The findings of the
      present study establish a foundation that can ensure the quality of NRSs for
      biologics in Korea, and it is expected to make a major contribution to the supply
      of high-quality biologics.

PMID- 28744355
TI  - Xylene Induces Oxidative Stress and Mitochondria Damage in Isolated Human
      Lymphocytes.
AB  - Xylene is a cyclic hydrocarbon and an environmental pollutant. It is also used in
      medical technology, paints, dyes, polishes and in many industries as a solvent;
      therefore, an understanding of the interaction between xylene and human
      lymphocytes is of significant interest. Biochemical assessment was used to
      demonstrate that exposure of lymphocytes to xylene induces cytotoxicity (at 6
      hr), generates intracellular reactive oxygen species, collapse of mitochondrial
      membrane potential, lysosomal injury, lipid peroxidation and depletion of
      glutathione (at 3 hr). The findings show that xylene triggers oxidative stress
      and organelle damage in lymphocytes. The results of our study suggest that the
      use of antioxidant, mitochondrial and lysosomal protective agents can be helpful
      for individuals subject to chronic exposure to xylene.

PMID- 28744356
TI  - Twenty-Eight-Day Repeated Inhalation Toxicity Study of Nano-Sized Neodymium Oxide
      in Male Sprague-Dawley Rats.
AB  - Neodymium is a future-oriented material due to its unique properties, and its use
      is increasing in various industrial fields worldwide. However, the toxicity
      caused by repeated exposure to this metal has not been studied in detail thus
      far. The present study was carried out to investigate the potential inhalation
      toxicity of nano-sized neodymium oxide (Nd2O3) following a 28-day repeated
      inhalation exposure in male Sprague-Dawley rats. Male rats were exposed to nano
      sized Nd2O3-containing aerosols via a nose-only inhalation system at doses of 0
      mg/m3, 0.5 mg/m3, 2.5 mg/m3, and 10 mg/m3 for 6 hr/day, 5 days/week over a 28-day
      period, followed by a 28-day recovery period. During the experimental period,
      clinical signs, body weight, hematologic parameters, serum biochemical
      parameters, necropsy findings, organ weight, and histopathological findings were
      examined; neodymium distribution in the major organs and blood, bronchoalveolar
      lavage fluid (BALF), and oxidative stress in lung tissues were analyzed. Most of
      the neodymium was found to be deposited in lung tissues, showing a dose-dependent
      relationship. Infiltration of inflammatory cells and pulmonary alveolar
      proteinosis (PAP) were the main observations of lung histopathology. Infiltration
      of inflammatory cells was observed in the 2.5 mg/m3 and higher dose treatment
      groups. PAP was observed in all treatment groups accompanied by an increase in
      lung weight, but was observed to a lesser extent in the 0.5 mg/m3 treatment
      group. In BALF analysis, total cell counts, including macrophages and
      neutrophils, lactate dehydrogenase, albumin, interleukin-6, and tumor necrosis
      factor-alpha, increased significantly in all treatment groups. After a 4-week
      recovery period, these changes were generally reversed in the 0.5 mg/m3 group,
      but were exacerbated in the 10 mg/m3 group. The lowest-observed-adverse-effect
      concentration of nano-sized Nd2O3 was determined to be 0.5 mg/m3, and the target
      organ was determined to be the lung, under the present experimental conditions in
      male rats.

PMID- 28744357
TI  - Evaluation of the Effect of Pentoxifylline on Cisplatin-Induced Testicular
      Toxicity in Rats.
AB  - Chemotherapy is associated with male infertility. Cisplatin (cis-diamminedichloro
      platinum (II) (CDDP) as a chemotherapy medication used to treat a number of
      cancers has been reported to most likely induce testicular toxicity.
      Administration of antioxidants, such as pentoxifylline (PTX) may reduce some
      Adverse Drug Reactions (ADRs) of CDDP. Therefore, this study investigated the
      potentially protective effects of PTX on CDDP-induced testicular toxicity in
      adult male rats. For this purpose, 42 male rats were randomly divided into 7
      groups. The rats were orally pretreated with PTX at the 3 doses of 75, 150, and
      300 mg/kg once a day for 14 successive days. On the 14th day of the study, they
      were intraperitoneally (IP) administered with a single dose of CDDP (7 mg/kg).
      Finally, the sperm/testis parameters, serum levels of reproductive hormones,
      including testosterone, Luteinizing Hormone (LH), and Follicle Stimulating
      Hormone (FSH) as the pivotal endocrine factors controlling testicular functions,
      and histopathological changes of testis tissue were examined. Pretreatment with
      the two doses of 75 and 150 mg/kg PTX indicated significant increases in the
      sperm count and motility induced by CDDP administration. The right and
      significantly left testis weights were decreased following the treatment with 300
      mg/kg of PTX plus CDDP. However, 75 mg/kg of PTX plus CDDP showed the best near
      to-normal histopathological features. The results demonstrated that PTX alone
      enhanced some parameters, such as the sperm count, while reducing other
      parameters, including sperm fast motility and germ layer thickness. Furthermore,
      despite testosterone or LH levels, the mean serum FSH level was significantly
      augmented by the doses of 75 and 150 mg/kg. It was concluded that PTX
      administration cannot reduce CDDP-induced testicular toxicity even at high doses
      (e.g., 300 mg/kg), while it seemed to partially intensify CDDP toxicity effects
      at a dose of 75 mg/kg. Thus, further research is required in this regard.

PMID- 28744358
TI  - Oral squamous cell cancer protein-protein interaction network interpretation in
      comparison to esophageal adenocarcinoma.
AB  - AIM: The aim of this study is to present the oral Squamous Cell Cancer protein
      protein interaction network interpretation in comparison to esophageal
      adenocarcinoma. BACKGROUND: Oral squamous cell cancer (OSCC) is a common disease
      worldwide, with poor prognosis and limited treatment. Thus, introducing molecular
      markers through network analysis can be helpful. METHODS: STRING database (DB)
      was applied for network construction through Cytoscape 3.4.0. Clue GO handled the
      gene annotation for the retrieved clusters. Eight proteins were indicated to be
      differential in the network constitution. RESULTS: The centrality and clustering
      analysis indicate that TP53 plays an over-significant role in network integrity
      among eight most central proteins including TP53, AKT1, EGFR, MYC, JUN, CDH1,
      CCND1, and CTNNB1. The suggested biomarker set is very similar to the related
      biomarker panel of esophageal adenocarcinoma. CONCLUSION: The ontology analysis
      implies that the prominent proteins are involved in regulation of smooth muscle
      cell proliferation, regulation of fibroblast proliferation, and response to UV-A
      processes. In conclusion, these proteins and their associated biological
      processes may be more critical compared to other reported biomarkers for OSCC.
      Nevertheless, validation studies are required for confirming the pivotal role of
      potential candidates. Similar biomarker panel of this disease and esophagus
      adenocarcinoma is corresponded to the origin of the two malignancies.

PMID- 28744359
TI  - Influence of hydrogen-occluding-silica on migration and apoptosis in human
      esophageal cells in vitro.
AB  - In the last decade, many studies have shown that hydrogen gas or hydrogen water
      can reduce the levels of reactive oxygen species in the living body. Molecular
      hydrogen has antioxidant and antiapoptotic effects and a preventive effect on
      oxidative stress-induced cell death. In the present study, we investigated
      solidified hydrogen-occluding-silica (H2-silica) that can release molecular
      hydrogen into cell culture medium because the use of hydrogen gas has strict
      handling limitations in hospital and medical facilities and laboratories, owing
      to its physicochemical characteristics. Human esophageal squamous cell carcinoma
      (KYSE-70) cells and normal human esophageal epithelial cells (HEEpiCs) were used
      to investigate the effects of H2-silica on cell viability and proliferation. Cell
      migration was examined with wound healing and culture-insert migration assays.
      The intracellular levels of reactive oxygen species were evaluated with a
      nitroblue tetrazolium assay. To assess the apoptotic status of the cells, the
      Bax/Bcl-2 ratio and cleaved caspase-3 were analyzed by western blot. The results
      showed that KYSE-70 cells and HEEpiCs were generally inhibited by H2-silica
      administration, and there was a significant proliferation-inhibitory effect in an
      H2-silica concentration-dependent manner compared with the control group (P <
      0.05) in KYSE-70. Apoptosis-inducing effect on KYSE-70 cells was observed in 10,
      300, 600, and 1,200 ppm H2-silica, and only 1,200 ppm H2-silica caused a 2.4-fold
      increase in apoptosis in HEEpiCs compared with the control group as the index of
      Bax/Bcl-2. H2 silica inhibited cell migration in KYSE-70 cells, and high
      concentrations had a cytotoxic effect on normal cells. These findings should
      provide insights into the mechanism of inhibition of H2-silica on human cancer
      cells in vitro.

PMID- 28744360
TI  - Effect of intravenous anesthesia with propofol versus isoflurane inhalation
      anesthesia in postoperative pain of inguinal herniotomy: a randomized clinical
      trial.
AB  - Postoperative pain is a common problem after inguinal herniotomy. We aimed to
      compare the intravenous anesthesia effects of propofol and isoflurane inhalation
      anesthesia on postoperative pain after inguinal herniotomy. In a randomized
      clinical trial, 102 eligible patients were selected based on inclusion and
      exclusion criteria and were randomly divided in two groups. In the first group,
      propofol was used for the maintenance of anesthesia, while isoflurane was used in
      the second group. The patient's heart rate, systolic and diastolic blood pressure
      and oxygen saturation before, during and after surgery, recovery time and
      postoperative pain were measured immediately, 2, 4 and 6 hours after surgery and
      compared between two groups. T-test, and repeated measurement test were used for
      statistical analysis. No statistically significant differences were observed in
      heart rate, blood pressure and oxygen saturation levels between the two groups (P
      > 0.05). Propofol has higher effect in easing postoperative pain of patients than
      isoflurane, but no difference in postoperative complications, including chills,
      nausea and vomiting, occurs in both two groups. Propofol is effective in
      declining the postoperative pain of patients after anesthesia in comparison with
      isoflurane. Moreover, due to the antioxidant, anti-inflammatory and analgesic
      properties of propofol, it is preferred to isoflurane and the authors recommended
      it to be used.

PMID- 28744362
TI  - Protective effects of hydrogen rich water on the intestinal ischemia/reperfusion
      injury due to intestinal intussusception in a rat model.
AB  - This study aimed to investigate the protective effects of hydrogen rich water on
      the intestinal ischemia/reperfusion (I/R) injury in a rat intestinal
      intussusception (II) model. Ninety Sprague-Dawley rats were randomly assigned
      into three groups (n = 30 per group). In sham group, rats received laparotomy,
      and the intestine was exposed for 15 minutes without II. In I/R + saline group
      and I/R + hydrogen group, rats received II after laparotomy and then intestine
      was relocated 8 hours later, followed by immediately intraperitoneal injection of
      normal saline and hydrogen rich water (HRW) (5 mL/kg), respectively. One hour
      later, the intestine was collected for hematoxylin-eosin staining and
      immunohistochemistry for apoptotic cells and 8-oxo-deoxyguanosine, and blood was
      harvested for detection of tumor necrosis factor-alpha, malondialdehyde and
      superoxide dismutase. Hematoxylin-eosin staining showed the intestinal mucosa was
      significantly damaged in I/R + saline group, which was markedly attenuated after
      HRW treatment. The serum tumor necrosis factor-alpha content increased
      significantly in I/R + saline group, but HRW treatment reduced serum tumor
      necrosis factor-alpha content as compared to I/R + saline group (P < 0.05). Serum
      malondialdehyde content and 8-oxo-deoxyguanosine positive cells in the intestine
      increased dramatically after II, but HRW significantly reduced them in
      I/R+hydrogen group (P < 0.05). In addition, superoxide dismutase activity reduced
      markedly and apoptotic cells increased in I/R + saline group as compared to sham
      group, but they HRW increased superoxide dismutase activity and reduced apoptotic
      cells significantly in I/R + hydrogen group (P < 0.05). Our results indicate
      hydrogen rich water is able to attenuate II induced intestinal I/R injury via
      inhibiting intestinal inflammation, attenuating intestinal/serum oxidative stress
      and reducing apoptotic intestinal cells.

PMID- 28744361
TI  - Argon attenuates the emergence of secondary injury after traumatic brain injury
      within a 2-hour incubation period compared to desflurane: an in vitro study.
AB  - Despite years of research, treatment of traumatic brain injury (TBI) remains
      challenging. Considerable data exists that some volatile anesthetics might be
      neuroprotective. However, several studies have also revealed a rather neurotoxic
      profile of anesthetics. In this study, we investigated the effects of argon 50%,
      desflurane 6% and their combination in an in vitro TBI model with incubation
      times similar to narcotic time slots in a daily clinical routine. Organotypic
      hippocampal brain slices of 5- to 7-day-old mice were cultivated for 14 days
      before TBI was performed. Slices were eventually incubated for 2 hours in an
      atmosphere containing no anesthetic gas, argon 50% or desflurane 6% or both.
      Trauma intensity was evaluated via fluorescent imagery. Our results show that
      neither argon 50% nor desflurane 6% nor their combination could significantly
      reduce the trauma intensity in comparison to the standard atmosphere. However, in
      comparison to desflurane 6%, argon 50% displayed a rather neuroprotective profile
      within the first 2 hours after a focal mechanical trauma (P = 0.015). A 2-hour
      incubation in an atmosphere containing both gases, argon 50% and desflurane 6%,
      did not result in significant effects in comparison to the argon 50% group or the
      desflurane 6% group. Our findings demonstrate that within a 2-hour incubation
      time neither argon nor desflurane could affect propidium iodide-detectable cell
      death in an in vitro TBI model in comparison to the standard atmosphere, although
      cell death was less with argon 50% than with desflurane 6%. The results show that
      within this short time period processes concerning the development of secondary
      injury are already taking place and may be manipulated by argon.

PMID- 28744363
TI  - Medical gases for stroke therapy: summary of progress 2015-2016.
AB  - Stroke is a cerebrovascular disease with high mortality and morbidity. Despite
      extensive research, there are only a very limited number of therapeutic
      approaches suitable for treatment of stroke patients as yet. Mounting evidence
      has demonstrated that such gases as oxygen, hydrogen and hydrogen sulfide are
      able to provide neuroprotection after stroke. In this paper, we will focus on the
      recent two years' progress in the development of gas therapies of stroke and in
      understanding the molecular mechanisms underlying protection induced by medical
      gases. We will also discuss the advantages and challenges of these approaches and
      provide information for future study.

PMID- 28744364
TI  - Hydrogen sulfide therapy in brain diseases: from bench to bedside.
AB  - Hydrogen sulfide (H2S) has been recognized and studied for nearly 300 years, but
      past researches mainly focus on its toxicity effect. During the past two decades,
      the majority of researches have reported that H2S is a novel endogenous gaseous
      signal molecule in organisms, and play an important role in various systems and
      diseases. H2S is mainly produced by three enzymes, including cystathionine beta
      synthase, cystathionine gamma-lyase and 3-mercaptopyruvate sulfurtransferase
      along with cysteine aminotransferase. H2S had been firstly reported as a
      neuromodulator in the brain, because of its essential role in the facilitating
      hippocampal long-term potentiation at physiological concentration. It is
      subsequently reported that H2S may have relevance to neurologic disorders through
      antioxidative, anti-inflammatory, anti-apoptotic and additional effects. Recent
      basic medical studies and preclinical studies on neurologic diseases have
      demonstrated that the administration of H2S at physiological or pharmacological
      levels attenuates brain injury. However, the neuroprotective effect of H2S is
      concentration-dependent, only a comparatively low dose of H2S can provide
      beneficial effect. Herein, we review the neuroprotevtive role of H2S therapy in
      brain diseases from its mechanism to clinical application in animal and human
      subjects, and therefore provide the potential strategies for further clinical
      treatment.

PMID- 28744365
TI  - Comments and hypotheses on the mechanism of methane against ischemia/reperfusion
      injury.
AB  - As we all know, methane is a kind of fuel. Previous studies have shown that
      methanogens in the colon can react with carbon dioxide and hydrogen to produce
      methane. In a recent study, the anti-inflammatory effects of methane were shown
      in a dog model of small intestinal ischemia/reperfusion. The mechanism of this
      anti-inflammatory effect needs further investigation. Recently, studies have
      shown anti-inflammatory, anti-apoptotic and anti-oxidative effects of methane on
      different organic injuries. According to the results of these studies, we
      hypothesize that the initial effects of methane are to react with free radicals
      and enhance expression of antioxidase through forkhead box transcription factor
      class O pathway. The anti-inflammatory effect is following the anti-oxidative
      effect, and the anti-apoptotic effect relies on anti-inflammatory and anti
      oxidative effects.

PMID- 28744366
TI  - Advances in molecular mechanism of cardioprotection induced by helium.
AB  - Helium has been classified as a kind of inert gas that is not effortless to spark
      chemical reactions with other substances in the past decades. Nevertheless, the
      cognition of scientists has gradually changed accompanied with a variety of
      studies revealing the potential molecular mechanism underlying organ-protection
      induced by helium. Especially, as a non-anesthetic gas which is deficient of
      relevant cardiopulmonary side effects, helium conditioning is recognized as an
      emerging and promising approach to exert favorable effects by mimicking the
      cardioprotection of anesthetic gases or xenon. In this review we will summarize
      advances in the underlying biological mechanisms and clinical applicability with
      regards to the cardioprotective effects of helium.

PMID- 28744367
TI  - Hyperbaric oxygen therapy of spinal cord injury.
AB  - Spinal cord injury (SCI) is a complex disease process that involves both primary
      and secondary mechanisms of injury and can leave patients with devastating
      functional impairment as well as psychological debilitation. While no curative
      treatment is available for spinal cord injury, current therapeutic approaches
      focus on reducing the secondary injury that follows SCI. Hyperbaric oxygen (HBO)
      therapy has shown promising neuroprotective effects in several experimental
      studies, but the limited number of clinical reports have shown mixed findings.
      This review will provide an overview of the potential mechanisms by which HBO
      therapy may exert neuroprotection, provide a summary of the clinical application
      of HBO therapy in patients with SCI, and discuss avenues for future studies.

PMID- 28744368
TI  - Subacute normobaric oxygen and hyperbaric oxygen therapy in drowning, reversal of
      brain volume loss: a case report.
AB  - A 2-year-old girl experienced cardiac arrest after cold water drowning. Magnetic
      resonance imaging (MRI) showed deep gray matter injury on day 4 and cerebral
      atrophy with gray and white matter loss on day 32. Patient had no speech, gait,
      or responsiveness to commands on day 48 at hospital discharge. She received
      normobaric 100% oxygen treatment (2 L/minute for 45 minutes by nasal cannula,
      twice/day) since day 56 and then hyperbaric oxygen treatment (HBOT) at 1.3
      atmosphere absolute (131.7 kPa) air/45 minutes, 5 days/week for 40 sessions since
      day 79; visually apparent and/or physical examination-documented neurological
      improvement occurred upon initiating each therapy. After HBOT, the patient had
      normal speech and cognition, assisted gait, residual fine motor and temperament
      deficits. MRI at 5 months after injury and 27 days after HBOT showed near
      normalization of ventricles and reversal of atrophy. Subacute normobaric oxygen
      and HBOT were able to restore drowning-induced cortical gray matter and white
      matter loss, as documented by sequential MRI, and simultaneous neurological
      function, as documented by video and physical examinations.

PMID- 28744369
TI  - Novel complement factor H gene mutation causing atypical haemolytic uraemic
      syndrome: early Eculizumab prevents acute dialysis.
AB  - We describe the clinical course and response to treatment of atypical haemolytic
      uraemic syndrome (aHUS) in two sisters presenting to our hospital 6 years apart
      with a novel complement factor H mutation that has not been described previously
      in literature and demonstrates the genetic complexity of this ultra-rare disease.
      The contrast in course and outcome of disease between the two sisters highlights
      the rapid evolution of management of aHUS, the importance of rapidly establishing
      a diagnosis, and how minimizing time to eculizumab therapy significantly reduces
      associated morbidity and mortality.

PMID- 28744370
TI  - Unexpected differences in the population genetics of phasmavirids (Bunyavirales)
      from subarctic ponds.
AB  - Little is known of the evolution of RNA viruses in aquatic systems. Here, we
      assess the genetic connectivity of two bunyaviruses (Kigluaik phantom
      orthophasmavirus or KIGV and Nome phantom orthophasmavirus or NOMV) with
      zooplanktonic hosts from subarctic ponds. We expected weak genetic structure
      among populations as the hosts (phantom midges) have a terrestrial winged
      dispersal stage. To test whether their respective viruses mirror this structure,
      we collected and analyzed population datasets from 21 subarctic freshwater ponds
      and obtained sequences from all four genes in the viral genomes. Prevalence
      averaged 66 per cent for 514 host specimens and was not significantly different
      between recently formed thaw ponds and glacial ponds. Unexpectedly, KIGV from
      older ponds showed pronounced haplotype divergence with little evidence of
      genetic connectivity. However, KIGV populations from recent thaw ponds appeared
      to be represented by a closely related haplotype group, perhaps indicating a
      genotypic dispersal bias. Unlike KIGV, NOMV had modest structure and diversity in
      recently formed thaw ponds. For each virus, we found elevated genetic diversity
      relative to the host, but similar population structures to the host. Our results
      suggest that non-random processes such as virus-host interactions, genotypic
      bias, and habitat effects differ among polar aquatic RNA viruses.

PMID- 28744372
TI  - COLQ-mutant Congenital Myasthenic Syndrome with Microcephaly: A Unique Case with
      Literature Review.
AB  - Congenital Myasthenic Syndrome (CMS) is a group of inherited neuromuscular
      junction disorders caused by defects in several genes. Clinical features include
      delayed motor milestones, recurrent respiratory illnesses and variable fatigable
      weakness. The central nervous system involvement is typically not part of the
      CMS. We report here a Saudi girl with genetically proven Collagen Like Tail
      Subunit Of Asymmetric Acetylcholinesterase (COLQ) mutation type CMS who has
      global developmental delay, microcephaly and respiratory failure. We have
      reviewed the literature regarding COLQ-type CMS and to the best of our knowledge
      this is the first ever reported association of congenital myasthenia syndrome
      with microcephaly.

PMID- 28744371
TI  - Diverse and highly recombinant anelloviruses associated with Weddell seals in
      Antarctica.
AB  - The viruses circulating among Antarctic wildlife remain largely unknown. In an
      effort to identify viruses associated with Weddell seals (Leptonychotes
      weddellii) inhabiting the Ross Sea, vaginal and nasal swabs, and faecal samples
      were collected between November 2014 and February 2015. In addition, a Weddell
      seal kidney and South Polar skua (Stercorarius maccormicki) faeces were
      opportunistically sampled. Using high throughput sequencing, we identified and
      recovered 152 anellovirus genomes that share 63-70% genome-wide identities with
      other pinniped anelloviruses. Genome-wide pairwise comparisons coupled with
      phylogenetic analysis revealed two novel anellovirus species, tentatively named
      torque teno Leptonychotes weddellii virus (TTLwV) -1 and -2. TTLwV-1 (n = 133,
      genomes encompassing 40 genotypes) is highly recombinant, whereas TTLwV-2 (n =
      19, genomes encompassing three genotypes) is relatively less recombinant. This
      study documents ubiquitous TTLwVs among Weddell seals in Antarctica with frequent
      co-infection by multiple genotypes, however, the role these anelloviruses play in
      seal health remains unknown.

PMID- 28744373
TI  - Quantitative Analysis of Macular Inner Retinal Layer Using Swept-Source Optical
      Coherence Tomography in Patients with Optic Tract Syndrome.
AB  - OBJECTIVE: To evaluate macular inner retinal layers using swept-source optical
      coherence tomography (SS-OCT) in patients with homonymous hemianopia due to optic
      tract syndrome (OTS). METHODS: Sixteen eyes of 8 patients with OTS were studied.
      The macular retinal nerve fiber layer (mRNFL), ganglion cell layer and inner
      plexiform layer (GCL + IPL), and mRNFL and GCL + IPL (GCC) were measured by SS
      OCT (DRI OCT-1 Atlantis(r)).The scanned area was divided into eight regions and
      two hemiretinae. Each retinal thickness of the OTS group was compared with that
      of the 25 control subjects. RESULTS: The GCC thickness in the ipsilateral eyes
      was significantly reduced in all regions, although predominant thinning of the
      GCC in the contralateral eyes was found in the nasal region. The GCC + IPL
      thickness was preferentially reduced at the temporal regions in the ipsilateral
      eyes and at the nasal regions in the contralateral eyes. The reduction rate of
      the GCL + IPL thickness was 29.6% at the temporal hemiretina in the ipsilateral
      eyes and 35.2% at the nasal hemiretina in the contralateral eyes. CONCLUSION: We
      found preferential loss of the GCC + IPL thickness corresponding to the hemifield
      defects in each eye. Quantitative analysis by SS-OCT is capable of detecting the
      characteristic RGC loss due to OTS.

PMID- 28744374
TI  - Effect of the Holiday Season on Weight Gain: A Narrative Review.
AB  - Several studies suggest that the holiday season, starting from the last week of
      November to the first or second week of January, could be critical to gaining
      weight. This study aims to review the literature to determine the effects of the
      holidays on body weight. In studies of adults, a significant weight gain was
      consistently observed during this period (0.4 to 0.9 kg, p < 0.05). The only
      study in college students found an effect on body fat but not on weight (0.1 kg,
      p = 0.71). The only study found in children did not show an effect on BMI
      percentile (-0.4%, p > 0.05) during this period. Among individuals with obesity
      who attempt to lose weight, an increase in weight was observed (0.3 to 0.9 kg,
      significant in some but not in all studies), as well as increase in weight in
      motivated self-monitoring people (0.4 to 0.6%, p < 0.001). Programs focused on
      self-monitoring during the holidays (phone calls and daily mailing) appeared to
      prevent weight gain, but information is limited. The holiday season seems to
      increase body weight in adults, even in participants seeking to lose weight and
      in motivated self-monitoring people, whereas in children, adolescents, and
      college students, very few studies were found to make accurate conclusions.

PMID- 28744375
TI  - Determinants of Walking among Middle-Aged and Older Overweight and Obese Adults:
      Sociodemographic, Health, and Built Environmental Factors.
AB  - BACKGROUND: This study examined the association between selected
      sociodemographic, health, and built environmental factors and walking behaviors
      of middle-aged and older overweight/obese adults. METHODS: Subjective data were
      obtained from surveys administered to community-dwelling overweight/obese adults
      aged >=50 years residing in four Texas cities from October 2013 to June 2014,
      along with objective data on neighborhood walkability (Walk ScoreTM).
      Multivariate logistic regression identified factors predicting the odds of
      walking the recommended >=150 minutes per week for any purpose. RESULTS: Of 253
      participants, the majority were non-Hispanic white (81.8%), married (74.5%), and
      male (53.4%) and reported an annual income of >=$50,000 (65.5%). Approximately,
      half were employed (49.6%) or had at least a college degree (51.6%). Walking the
      recommended >=150 minutes per week for any purpose (n = 57, 22.5%) was
      significantly associated with having at least a college degree (OR = 5.55, 95% CI
      = 1.79-17.25), having no difficulty walking a quarter of a mile (OR = 5.18, 95%
      CI = 1.30-20.83), and being unemployed (OR = 3.25, 95% CI = 1.18-8.93) as well as
      perceived presence of sidewalks/protected walkways (OR = 3.56, 95% CI = 1.10
      11.50) and perceived absence of distracted drivers in the neighborhood (OR =
      4.08, 95% CI = 1.47-11.36). CONCLUSION: Addressing neighborhood conditions
      related to distracted drivers and pedestrian infrastructure may promote walking
      among middle-aged and older overweight/obese individuals.

PMID- 28744376
TI  - Prevalence of the Metabolic Syndrome in Central and South American Immigrant
      Residents of the Washington, DC, Area.
AB  - The objective of this study was to estimate the prevalence of Metabolic Syndrome
      (MetS) and its risk components and then compare differences in the risk
      components among low-income, uninsured Central and South American recent
      immigrants to the USA. This cross-sectional survey sampled 1,042 adult patients
      from a medical clinic in metropolitan Washington, DC. The overall prevalence of
      the MetS was 26.9% estimated using the modified harmonized definition. The most
      common abnormal metabolic indicator for women was an elevated BMI >= 30 kg/m2
      (36.1%), while, for men, it was an elevated triglyceride level (46.5%). The risk
      of abnormal MetS indicators increased steadily with increasing BMI. The abnormal
      indicator combination identifying the most subjects with the MetS included the
      following: high triglycerides, low HDL cholesterol, and obesity. MetS rates were
      highest among subjects from El Salvador and Honduras, 31.3% and 28.0%,
      respectively, and lowest among subjects from Bolivia (21.7%). Dyslipidemia and
      high BMI increased the likelihood of having the MetS, which is consistent with
      studies on Mexican Americans in the San Antonio Heart Study and studies within
      Central and South American countries. This study adds new baseline
      epidemiological data for largely understudied, low-income, and mostly recent
      immigrant groups.

PMID- 28744377
TI  - Missed Testing Opportunities for HIV Screening and Early Diagnosis in an Urban
      Tertiary Care Center.
AB  - Newark, New Jersey, is disproportionally affected by HIV with one of the highest
      prevalence rates in the United States. Rutgers New Jersey Medical School is a
      major healthcare provider to Newark's underserved population and has implemented
      a HIV testing program that can diagnose and link newly diagnosed individuals to
      care. We conducted a retrospective chart review of all new patients seen in the
      Infectious Disease Practice from January 1, 2013, to December 31, 2014, to
      determine the proportion of patients with a missed testing opportunity (MTO)
      (patients with a new HIV diagnosis with an encounter at the institution in the 1
      year prior to their first appointment). 117 newly diagnosed patients were
      identified. 36 (31%) had at least one MTO. A total of 34 (29%) of newly diagnosed
      patients had AIDS at presentation and 17% had CD4 counts of 50 cells/MUL (p value
      0.5). The two most common locations of a missed testing opportunity were the
      hospital ED (45%) and subspecialty clinics (37%). This study demonstrates that,
      even in a high prevalence institution with HIV counseling, testing, and referral
      service, HIV screening is lacking at multiple points of care and patients are
      missing opportunities for earlier diagnosis and treatment.

PMID- 28744378
TI  - Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal
      Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats.
AB  - Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of
      muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal
      sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve
      electrical stimulation (TANES) has been shown to activate the central pattern
      generator (CPG) and improve the locomotion recovery of spinal contused rats.
      Electroacupuncture (EA) is a traditional Chinese medical practice which has been
      proven to have a neural protective effect. Here, we examined the effects of TANES
      and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats,
      respectively. From the third day postsurgery, rats in the TANES group were
      treated 5 times a week and those in the EA group were treated once every other
      day. Four weeks later, both TANES and EA showed a significant impact in promoting
      survival of lumbar motor neurons and expression of choline acetyltransferase
      (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the
      expression of neurotrophin-3 (NT-3) in the same spinal cord segment was
      significantly increased. These findings suggest that TANES and EA can augment the
      expression of NT-3 in the lumbar spinal cord that appears to protect the motor
      neurons as well as alleviate muscle atrophy.

PMID- 28744379
TI  - Differences in Healing of a Horizontal Root Fracture as Seen on Conventional
      Periapical Radiography and Cone-Beam Computed Tomography.
AB  - Different locations and healing patterns of horizontal root fractures bear
      different prognoses. Conventional periapical radiographs have been routinely used
      for the evaluation of the locations and healing of horizontal root fractures,
      with the limitation of presenting two-dimensional images. The three-dimensional
      imaging technology, cone-beam computed tomography (CBCT), has recently gained
      interest in dental traumatology, in particular for locating and diagnosing root
      fractures. However, the assessment of healing patterns of horizontal root
      fracture using CBCT compared to conventional radiographs has not been
      established. This case report describes the different healing patterns evaluated
      by two-dimensional radiographs and CBCT of a horizontally root-fractured
      maxillary right central incisor treated with mineral trioxide aggregate (MTA)
      with a two-year follow-up. The findings suggest that the healing patterns of
      horizontal root fractures seen on conventional radiographs and CBCT may be
      different.

PMID- 28744380
TI  - Orthodontic Treatment and Maxillary Anterior Segmental Distraction Osteogenesis
      of a Subject with Williams-Beuren Syndrome and Isolated Cleft Palate: A Long-Term
      Follow-Up from the Age of 5 to 24 Years.
AB  - Williams-Beuren syndrome (WBS) is a rare multisystem disorder caused by a
      hemizygous deletion of the elastin gene on chromosome 7q11.23. WBS patients have
      characteristic skeletal features and dental anomalies accompanied by mental
      retardation, a friendly outgoing personality, and mild to moderate intellectual
      disability or learning problems. In this case report, we present the combined
      orthodontic and surgical treatment of a WBS patient with an isolated cleft palate
      through a long-term follow-up from the age of 5 to 24 years. During the period of
      active treatment, comprehensive orthodontic treatment combined with maxillary
      anterior segmental distraction osteogenesis and prosthetic treatment using dental
      implants were effective in dramatically improving the patient's malocclusion. The
      patient's mental abilities and the cooperation shown by the patient and her
      family were crucial for the success of this complex and long-term treatment
      course.

PMID- 28744381
TI  - A Case of Strongyloidiasis: An Immigrant Healthcare Worker Presenting with
      Fatigue and Weight Loss.
AB  - BACKGROUND: Strongyloides stercoralis is an intestinal nematode parasite
      classified as a soil-transmitted helminth, endemic in tropical and subtropical
      regions. Strongyloides stercoralis can remain dormant for decades after the
      initial infection. CASE: We describe a patient who was diagnosed with
      Strongyloides stercoralis infection three weeks after a left inguinal hernia
      repair and discuss approaches to prevention, diagnosis, and treatment.
      CONCLUSIONS: Physicians in the United States often miss opportunities to identify
      patients with chronic strongyloidiasis. Symptoms may be vague and screening tests
      have limitations. We review current strategies for diagnosis and treatment of
      chronic intestinal strongyloidiasis in immigrant patients who have significant
      travel history to tropical regions and discuss the clinical features and
      management of the infection.

PMID- 28744382
TI  - Multimodal Imaging in a Patient with Hemidystonia Responsive to GPi Deep Brain
      Stimulation.
AB  - BACKGROUND: Dystonia is a syndrome with varied phenomenology but our
      understanding of its mechanisms is deficient. With neuroimaging techniques, such
      as fiber tractography (FT) and magnetoencephalography (MEG), pathway connectivity
      can be studied to that end. We present a hemidystonia patient treated with deep
      brain stimulation (DBS). METHODS: After 10 years of left axial hemidystonia, a 45
      year-old male underwent unilateral right globus pallidus internus (GPi) DBS.
      Whole brain MEG before and after anticholinergic medication was performed prior
      to surgery. 26-direction diffusion tensor imaging (DTI) was obtained in a 3 T MRI
      machine along with FT. The patient was assessed before and one year after surgery
      by using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: In the
      eyes-closed MEG study there was an increase in brain coherence in the gamma band
      after medication in the middle and inferior frontal region. FT demonstrated over
      50% more intense ipsilateral connectivity in the right hemisphere compared to the
      left. After DBS, BFMDRS motor and disability scores both dropped by 71%.
      CONCLUSION: Multimodal neuroimaging techniques can offer insights into the
      pathophysiology of dystonia and can direct choices for developing therapeutics.
      Unilateral pallidal DBS can provide significant symptom control in axial
      hemidystonia poorly responsive to medication.

PMID- 28744383
TI  - Previable Preeclampsia Diagnosed by Renal Biopsy in Setting of Novel Diagnosis of
      C4 Glomerulopathy.
AB  - BACKGROUND: Preeclampsia diagnosed before 20 weeks' gestational age is a rare
      entity, particularly without any predisposing factors. We report a case of
      preeclampsia occurring prior to 20 weeks' gestational age in the setting of a
      novel diagnosis of C4 glomerulopathy. CASE: A G3P0020 at 18 weeks presented with
      new onset hypertension and proteinuria, requiring multiple antihypertensive
      agents to maintain control. Renal biopsy demonstrated thrombotic microangiopathic
      lesions and glomerular endotheliosis. C4-dominant staining and numerous
      subendothelial and mesangial electron dense deposits were found within the
      glomerulus. With no other definable etiologies, preeclampsia was diagnosed. She
      developed posterior reversible encephalopathic syndrome and pregnancy termination
      was recommended. CONCLUSION: The lectin complement pathway may play a role in the
      pathophysiology of severe, early onset preeclampsia. Renal biopsy may play an
      integral role in diagnosis.

PMID- 28744384
TI  - A Unique Case of Muscle-Invasive Metastatic Breast Cancer Mimicking Myositis.
AB  - Breast cancer rarely metastasizes to the muscles, and it is even more unusual for
      this phenomenon to result in airway compromise. We present a unique case of an 84
      year-old female who presented with neck swelling and upper airway obstruction due
      to metastatic breast cancer invading the sternocleidomastoid muscles. After
      establishing the diagnosis and discussing possible treatment options, the patient
      elected for antiestrogen therapy, palliative tracheostomy, radiation therapy, and
      hospice services.

PMID- 28744385
TI  - Everolimus Implicated in Case of Severe Gastrointestinal Hemorrhage.
AB  - Breast cancer remains the leading cause of cancer and the third leading cause of
      cancer related deaths among our population with an estimated number of 246,660
      new cases and 40,450 deaths in 2016. With treatment advancements, including
      targeted agents such as Everolimus, a mammalian target of rapamycin (mTOR)
      inhibitor, survivability and quality of life continue to improve. However, with
      the use of these agents come adverse effects, some of which are still being
      characterized. Our case demonstrates recurrent episodes of gastrointestinal
      bleeding in a 60-year-old woman being treated with Everolimus for progressive
      metastatic breast cancer. On endoscopy, bleeding was secondary to erosive
      gastritis. Previous case reports have described bleeding due to gastric antral
      vascular ectasia (GAVE), which was described in two prior reported cases. In our
      case, bleeding also occurred on a reduced dose of Everolimus compared to what is
      previously reported (5 mg versus 10 mg). As a result of her gastrointestinal
      bleeding, she required multiple endoscopic interventions including argon plasma
      coagulation and multipolar heater probe to achieve hemostasis. This is the first
      case reported of gastrointestinal bleeding not consistent with GAVE and occurring
      while being on a reduced dose of Everolimus. It is important to document our case
      so that the Gastroenterology and Hematology communities can be educated and made
      aware for their patient populations on Everolimus.

PMID- 28744386
TI  - Idiopathic Bilateral Suprachoroidal Haemorrhage: A Rare Case Presentation.
AB  - 55-year-old male presented with sudden onset painful diminution of vision in both
      eyes. On local examination, his visual acuity was FC at 2 metres in right eye and
      FC at 1 m in left eye. The IOP in right eye was 46 mm Hg and 44 mm Hg in left
      eye. The patient was admitted and started on injection mannitol, oral syrup
      glycerol, and oral acetazolamide. Locally, timolol maleate and brimonidine were
      also started. The next day, his IOP was 17 mm Hg bilaterally but his visual
      acuity deteriorated to FC 1 m in right eye and hand movement in left eye with
      inaccurate projection of rays in both eyes. USG B-scan was performed which
      revealed bilateral choroidal detachment. The echotexture of fluid was suggestive
      of haemorrhage. As the IOP was controlled, systemic hyperosmotic/antiglaucoma
      agents were withdrawn in stepwise fashion over next two days. The patient was
      started on oral prednisolone. At 2 weeks, the visual acuity in both eyes was only
      perception of light, with inaccurate PR. IOP was 10 mm Hg in both eyes. USG B
      scan revealed resorption of the hemorrhage, with partial resolution of the
      choroidal detachment. The final BCVA was 6/18 and 6/12 in right and left eye.

PMID- 28744387
TI  - A Case of an Insufficiency Fracture of the Medial Proximal Tibia Secondary to
      Osteomalacia Associated with Long-Term Saccharated Ferric Oxide Administration.
AB  - This article presents a case of insufficiency fracture of medial proximal tibia
      caused by long-term administration of saccharated ferric oxide (SFO) in a 77-year
      old female. In this case, 2-year administration of SFO for iron deficit anemia
      induced hypophosphatemic osteomalacia and finally resulted in an insufficiency
      fracture of medial proximal tibia. Hypophosphatemia and pain due to the
      insufficiency fracture were recovered promptly by withdrawing SFO administration
      and rest. This case represented varus deformity of the knee associated with
      osteoarthritis, which may also cause the insufficiency fracture of medial
      proximal tibia in addition to osteomalacia due to long-term administration of
      SFO. Long-term SFO administration should be avoided because of a definitive risk
      of osteomalacia and fragile fracture.

PMID- 28744388
TI  - Limb Amputation after Multiple Treatments of Tenosynovial Giant Cell Tumour:
      Series of 4 Dutch Cases.
AB  - In Tenosynovial Giant Cell Tumours (TGCT), previously named Pigmented
      Villonodular Synovitis (PVNS), a distinction is made between a single nodule
      (localized-type) and multiple nodules (diffuse-type). Diffuse-type is considered
      locally aggressive. Onset and extermination of this orphan disease remain
      unclear. Surgical resection is the most commonly performed treatment.
      Unfortunately, recurrences often occur (up to 92%), necessitating reoperations
      and adjuvant treatments. Once all treatments fail or if severe complications
      occur, limb amputation may become unavoidable. We describe four cases of above
      knee amputation after TGCT diagnosis.

PMID- 28744389
TI  - Tubercular Ulcer of Tongue in an Elderly Patient Masquerading as a Traumatic
      Ulcer.
AB  - Tuberculosis is still one of the most prevalent diseases in developing countries
      like Nepal. However, due to the effectiveness of DOTS therapy, vaccination, and
      education, the prevalence of tuberculosis has fallen in recent years. Although
      the pulmonary and extrapulmonary tuberculosis, especially the tubercular
      lymphadenitis, is still very common in our country, the tuberculosis of oral
      cavity is an uncommon condition. We present a case of an elderly male who
      presented with the complaint of nonhealing ulcer of lateral border of tongue for
      2-month duration which was masquerading as a traumatic ulcer due to sharp teeth
      adjacent to the lesion. Deep biopsy was taken under local anesthesia.
      Histopathological examination revealed that it was tuberculosis. Antitubercular
      therapy was then started which cured the lesion.

PMID- 28744390
TI  - Corrigendum to "New and Emerging Therapies for Osteoporosis".
AB  - [This corrects the article DOI: 10.4061/2010/318320.].

PMID- 28744391
TI  - Thyroid Disorders in Central Ghana: The Influence of 20 Years of Iodization.
AB  - BACKGROUND: Ghana began mandatory iodization of salt in 1996. This study compares
      the prevalence of thyroid disorders before and after the introduction of
      iodization. METHODS: This is a retrospective study of thyroid cases from the
      middle belt of Ghana between 1982 and 2014. To demonstrate a link between
      iodization and hyperthyroidism and autoimmunity, we compared the prevalence of
      hyperthyroidism and autoimmune thyroid disorders before and after the iodization
      programme. RESULTS: A total of 10,484 (7548 females, 2936 males) cases were
      recorded. The rate of thyroid cases seen was 343/100,000. Nontoxic nodular
      goiters (25.7%) and toxic nodular goiters (22.5%) represented the second
      commonest thyroid disorders recorded. The prevalence of hyperthyroid disorders
      seen after 1996 was significantly higher than the prevalence seen before the
      iodization (40.0 versus 21.1%, p < 0.001). The prevalence of autoimmune disorders
      recorded after iodization was significantly higher than that before the
      iodization programme started (22.3% versus 9.6%, p < 0.001). CONCLUSIONS: This
      study has revealed a significant increase in thyroid admissions in Central Ghana
      over the decades. A connection between iodine fortification and iodine-induced
      hyperthyroidism and between iodine fortification and autoimmune thyroiditis has
      been shown in this study.

PMID- 28744392
TI  - Ultrasound Risk Categories for Thyroid Nodules and Cytology Results: A Single
      Institution's Experience after the Adoption of the 2016 Update of Medical
      Guidelines by the American Association of Clinical Endocrinologists and
      Associazione Medici Endocrinologi.
AB  - OBJECTIVES: In 2016, the American Association of Clinical Endocrinologists (AACE)
      and Associazione Medici Endocrinologi (AME) released updated guidelines for the
      diagnosis and management of thyroid nodules. The aim of this study was to
      evaluate the AACE/AME recommendations for FNA in clinical practice, by comparing
      the (US) stratification risk and indications for FNA with cytologic results.
      METHODS: From May to December 2016, we collected the cytologic results from FNAs
      of nodules that were classified using a three-tier US category system (low,
      intermediate, and high risk). RESULTS: We obtained 859 FNAs from 598 patients:
      341 (39.7%) from low, 489 (56.9%) from intermediate, and 29 (3.4%) from high risk
      nodules. Of these, 88.5% and 74.9% of low and intermediate risk nodules,
      respectively, were cytologically benign, whereas 84.6% of high risk nodules had a
      moderate-to-elevated risk of malignancy or were malignant. If FNAs had been
      limited to intermediate risk nodules >20 mm, we would have missed 13/17 (76.5%)
      nodules that had moderate-to-elevated risk of malignancy or were malignant (11/13
      were malignant based on histology). CONCLUSIONS: A nonnegligible number of
      cytologically malignant nodules or nodules that were suspected to be malignant
      would be missed if intermediate US risk nodules <20 mm were not biopsied.

PMID- 28744393
TI  - Autophagic degradation of FOXO3a represses the expression of PUMA to block cell
      apoptosis in cisplatin-resistant osteosarcoma cells.
AB  - Autophagy and apoptosis are the two major modes of cell death, and autophagy
      usually inhibits apoptosis. The current understanding has shown that there is a
      complex crosstalk between the components of these two pathways. Here, we describe
      a transcriptional mechanism that links autophagy to apoptosis. We show that the
      cisplatin-resistant MG63-R12 and U2OS-R5 osteosarcoma sublines, in comparison to
      their parental MG63 and U2OS cells, respectively, exhibit increased autophagy but
      decreased apoptosis levels after treatment with cisplatin. We then used a
      microarray assay to examine the gene expression changes in these two cisplatin
      resistant sublines and found that the expression of the transcription factor
      FOXO3a was dramatically decreased. Pharmacological treatment with either 3
      methyladenine to inhibit autophagy or with rapamycin to activate autophagy in
      these two cisplatin-resistant sublines resulted in the accumulation or
      degradation of FOXO3a, respectively. Ectopic expression of FOXO3a in MG63-R12 and
      U2OS-R5 cells significantly enhanced cell sensitivity to cisplatin through a
      mechanism in which FOXO3a directly binds to the PUMA promoter and activates its
      expression, as well as its downstream event, the intrinsic apoptosis pathway.
      Importantly, this overexpression resulted in tumor growth inhibition in vivo. In
      conclusion, our results provide new insights into the molecular link between
      autophagy and apoptosis that involves a FOXO3a-mediated transcriptional
      mechanism. Importantly, our results may facilitate the development of therapeutic
      strategies for osteosarcoma patients who have become resistant to cisplatin
      therapy.

PMID- 28744394
TI  - A positive feedback loop of long noncoding RNA CCAT2 and FOXM1 promotes
      hepatocellular carcinoma growth.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies around the
      world. Long noncoding RNAs (lncRNAs) are greater than 200 nucleotides without
      protein-coding potential and play critical roles in tumorigenesis, cell
      differentiation, and cancer metastasis. Colon cancer-associated transcript 2
      (CCAT2), a newly identified lncRNA, was shown to be dysregulated in cancers.
      However, the functional role of CCAT2 in HCC remains questionable. In the present
      study, we found a significant upregulation of CCAT2 in HCC tissues as compared to
      non-tumor tissues. Functional assays showed that CCAT2 promotes cell growth in
      vivo and in vitro. In addition, we found a positive feedback loop between CCAT2
      and FOXM1. CCAT2 upregulates FOXM1 expression through interaction with, and
      suppression of, miR-34a, and FOXM1 activates CCAT2 transcription. We evaluated
      the therapeutic potential of ultrasound-targeted microbubble destruction (UTMD)
      mediated siRNA delivery to specifically target CCAT2. UTMD-mediated siCCAT2
      delivery significantly suppressed tumor growth in vivo. Thus, CCAT2-FOXM1 may be
      a novel target for the treatment of HCC.

PMID- 28744395
TI  - A bispecific antibody targeting IGF-IR and EGFR has tumor and metastasis
      suppressive activity in an orthotopic xenograft osteosarcoma mouse model.
AB  - Osteosarcoma is a highly aggressive bone cancer and the second most frequent
      cause of cancer-associated death in childhood and adolescence. Pulmonary
      metastases account for the high mortality rate in osteosarcoma patients.
      Therefore, novel therapeutic approaches, efficiently restraining the metastatic
      disease, are mandatory for a significant improvement of the currently poor
      patients' survival. Although initial studies with antibodies targeting insulin
      like growth factor receptor (IGF-IR) showed promising potential for the treatment
      of patients with bone and soft tissue sarcomas, phase II clinical trials revealed
      variable results, which implied activation of alternative signaling pathways
      leading to therapy resistance. Since a cross-talk between IGF-IR and the
      epidermal growth factor receptor (EGFR) has been demonstrated in several cancer
      types, co-targeting of these two receptors was considered in the present study as
      a valuable therapeutic strategy to overcome single-agent treatment resistance in
      osteosarcoma. The effects of IGF-IR and/or EGFR targeting by intraperitoneal
      administration of the monospecific IGF-IR antibody R1507 or the EGFR antibody
      Cetuximab or the bispecific IGF-IR/EGFR antibody XGFR* on primary tumor growth
      and pulmonary metastasis were investigated in an intratibial human xenograft
      osteosarcoma mouse model. In vitro functional assays demonstrated that targeting
      IGF-IR and EGFR didn't affect osteosarcoma cell viability, but inhibited ligand
      activated intracellular signaling and cell migratory capacity. The blocking
      potential of ligand-induced signaling in vitro was similar for all antibodies,
      but, in vivo, only XGFR* treatment significantly inhibited intratibial primary
      tumor growth and pulmonary metastasis. The therapeutic response to XGFR* was
      associated with an infiltration of innate immune system effector cells into the
      tumor microenvironment. Taken together, our study highlights the bispecific anti
      IGF-IR/EGFR antibody XGFR* as an innovative promising effective candidate for the
      treatment of metastatic osteosarcoma and provides the rationale for future
      clinical studies.

PMID- 28744396
TI  - LncRNA ZFAS1 promotes growth and metastasis by regulating BMI1 and ZEB2 in
      osteosarcoma.
AB  - Osteosarcoma (OS) is the most common malignant bone tumor in children and
      adolescents. LncRNAs have recently gained widespread attention and have been
      shown to have crucial roles in various biological regulatory processes. ZFAS1, a
      newly identified lncRNA, was shown to be dysregulated in several cancers.
      However, little is known about the alteration and functional significance of
      ZFAS1 in OS. In the present study, for the first time, we revealed a functional
      role of ZFAS1 on OS growth and metastasis. The expression of ZFAS1 was
      significantly overexpressed in OS samples and cell lines, and upregulation of
      ZFAS1 is significantly associated with unfavorable prognosis of OS patients.
      Functional assays also demonstrated that ZFAS1 enhanced the growth and metastatic
      ability of OS cells in vitro and in vivo. Mechanistically, we found that ZFAS1
      positively regulated malignant phenotypes by competitively binding the miR-200b
      and miR-200c and upregulating BMI1. ZFAS1 also interacted with ZEB2 and regulated
      ZEB2 protein stability. Furthermore, we demonstrated that SP1 functions as an
      upstream activated factor of ZFAS1. ZFAS1 may be a potential therapeutic target
      for OS tumorigenesis and progression.

PMID- 28744397
TI  - Long non-coding RNA DGCR5 is involved in the regulation of proliferation,
      migration and invasion of lung cancer by targeting miR-1180.
AB  - Accumulating studies have demonstrated that non-coding RNAs (ncRNAs), including
      small non-coding RNAs (small ncRNAs) and long non-coding RNAs (lncRNAs), are
      involved in tumor growth in lung cancer (LC). However, the specific role of DGCR5
      in LC progression is not yet clear. In the present study, we found that DGCR5 was
      downregulated and miR-1180 was upregulated in the sera and tissues of LC patients
      and was correlated with poor prognosis. We also found that DGCR5 suppressed
      proliferation, migration and invasion of LC cell lines H520 and H1299. In
      addition, a luciferase reporter gene assay was used to investigate the regulatory
      relationship between DGCR5 and miR-1180. Furthermore, we suggested that DGCR5
      inhibited the expression of AKT, GSK-3beta, and beta-catenin by targeting miR
      1180. Based on these findings, DGCR5 might serve as a potential target for the
      development of effective anti-neoplastic therapies in lung cancer.

PMID- 28744398
TI  - Kinase inhibitors of HER2/AKT pathway induce ERK phosphorylation via a FOXO
      dependent feedback loop.
AB  - Inhibitors of the HER2/PI3K/AKT pathway are being developed, and shown promise in
      clinical trials for various types of cancers. However, development of drug
      resistance is a challenging problem for therapy. Elucidating various adaptive
      pathways leading to resistance or reduced sensitivity to drugs targeting the
      HER2/PI3K/AKT pathway may provide new insights into countering the resistance.
      Epidermal growth factor receptor (EGFR, aka HER1), which can dimerize with HER2,
      can activate a cascade consisting of Ras/RAF/MEK/ERK, promoting tumorigenesis.
      Lapatinib inhibits the kinase activity of both HER1 and HER2. In the current
      study, we found that repeated treatment of HER2+ breast cancer cells with HER1/2
      inhibitor Lapatinib led to increased phosphorylation of RAF, MEK, and ERK, while
      suppressing HER1 phosphorylation and reduced the active form of Ras, indicating
      existence of factor(s) activating RAF/MEK/ERK by bypassing RAS activation.
      Notably, the Lapatinib treatment-induced phosphorylation of ERK was dependent on
      FOXO transcription factors, which are also activated by Lapatinib-mediated
      suppression of AKT. Moreover, the Lapatinib-induced phosphorylation of RAF and
      ERK is inhibited by a pan-PKC inhibitor. Furthermore, the Lapatinib induced
      increased ERK phosphorylation is correlated with increased stability of c-Myc,
      which is known to be stabilized by ERK-mediated phosphorylation. Together, these
      results suggest that chronic inhibition of the HER1/2 by Lapatinib triggers a
      feedback loop to activate RAF/MEK/ERK pathway, in a FOXO dependent but Ras
      independent manner.

PMID- 28744399
TI  - The addition of calcitriol or its synthetic analog EB1089 to lapatinib and
      neratinib treatment inhibits cell growth and promotes apoptosis in breast cancer
      cells.
AB  - In breast cancer the use of small molecule inhibitors of tyrosine kinase activity
      of the ERBB family members improves survival thus represents a valuable
      therapeutic strategy. The addition of calcitriol, the most active metabolite of
      vitamin D, or some of its analogs, to conventional anticancer drugs, including
      tyrosine kinase inhibitors (TKIs), has shown an increased effect on the
      inhibition of cancer cell growth. In this work, we have evaluated the effects and
      the mechanism of action of the combination of calcitriol or its analog EB1089
      with lapatinib or neratinib on EGFR and/or HER2 positive breast cancer cell
      lines. Lapatinib, neratinib, calcitriol and EB1089 inhibited breast cancer cell
      proliferation in a concentration-dependent manner. Addition of calcitriol or
      EB1089 to TKIs treatment induced more effective inhibiting effect on cell growth
      and AKT and MAPK phosphorylation than all compounds alone. The combined
      treatments incremented also the expression of active caspase 3 and induced cell
      death in two and three-dimensional cell culture and significantly inhibited
      anchorage-independent colony formation. Our results suggest that the addition of
      calcitriol or its analog EB1089 to conventional targeted therapies, including
      lapatinib or neratinib might be of benefit to patients with breast cancer,
      particularly those with an EGFR and/or HER2 positive phenotype.

PMID- 28744400
TI  - Hispidulin suppresses tumor growth and metastasis in renal cell carcinoma by
      modulating ceramide-sphingosine 1-phosphate rheostat.
AB  - Sphingosine 1-phosphate (S1P) rheostat is considered as a key signal that
      determines cell fate. This study aimed to report that hispidulin, a polyphenolic
      flavonoid, exerted anti-growth and anti-metastasis effects against renal cell
      carcinoma (RCC) by modulating the balance of ceramide-S1P. In vitro studies
      showed that hispidulin could effectively inhibit cell proliferation, cell
      migration, cell invasion, and epithelial-mesenchymal transition, and promote cell
      apoptosis in Caki-2 and A498 cell lines. Moreover, it also increased the
      ceramide/S1P ratio. Consistent with the in vitro findings, the efficacy of
      hispidulin in vivo showed that it effectively suppressed tumor growth and lung
      metastasis. Furthermore, the results revealed that hispidulin significantly
      suppressed the activity of sphingosine kinase 1 (Sphk1) in RCC cells; however, no
      significant change was observed in the mRNA or protein expression of Sphk1. The
      overexpression of Sphk1 could significantly abrogate the anti-growth and anti
      metastasis effects of hispidulin, whereas the siRNA-targeting Sphk1 or Sphk1
      inhibitor was able to augment the anticancer effects of hispidulin against RCC.
      Moreover, hispidulin interfered with the phosphorylation and translocation of
      Sphk1, leading to inhibitory effects of Sphk1 activity. In summary, the findings
      suggested that hispidulin suppressed tumor growth and metastasis by inhibiting
      the Sphk1 activity and consequently modulating ceramide-S1P rheostat. It also
      presented a new explanation for the antitumor mechanisms of hispidulin against
      RCC.

PMID- 28744401
TI  - Polyisoprenylated cysteinyl amide inhibitors induce caspase 3/7- and 8-mediated
      apoptosis and inhibit migration and invasion of metastatic prostate cancer cells.
AB  - Metastatic castration-resistant prostate cancer (mCRPC) is the most aggressive
      and deadly form of prostate cancer. It is characterized by the overexpression of
      epidermal growth factor receptors whose signals are mediated by small monomeric G
      proteins of the Ras superfamily. These require polyisoprenylation for functional
      activity. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) of
      polyisoprenylated methylated protein methyl esterase (PMPMEase) were developed as
      potential targeted therapies to mitigate excessive growth signaling in mCRPC
      either by inhibiting PMPMEase and/or perturbing the polyisoprenylation-dependent
      functional interactions. We investigated the effects of PCAIs on the viability of
      prostate cancer PC 3, DU 145, MDA PCa 2b, LNCaP and 22Rv1 cells, determined the
      effect of the PCAIs on PC 3 cell proliferation, survival and caspase-mediated
      apoptotic cell death. Metastatic PC 3 and DU 145 cell migration and invasion in
      the presence of NSL-BA-040 were determined using the scratch and matrigel
      invasion assays. We further investigated the effect of NSL-BA-040 on F-actin
      organization in TagRFP F-actin marker-transfected metastatic PC 3 cells. The
      PCAIs suppress mCRPC cell viability with EC50 values ranging from 1.3 to 4.0 uM
      for the most potent of the PCAIs against PC 3, DU 145, MDA PCa 2b, LNCaP and 22Rv
      cells. PCAIs induced apoptotic cell death in PC 3 and DU 145 cells as determined
      by annexin V/propidium iodide flow cytometry analysis through the activation of
      caspases 3 and 8 while also inhibiting migration and invasion through the
      disruption of F-actin organization. Taken together, our studies show the anti
      cancer effects on mCRPC cells through induction of caspase-mediated apoptosis and
      F-actin-mediated inhibition of cell motility and invasion thereby indicating the
      anti-tumor and anti-metastatic potential of the PCAIs.

PMID- 28744402
TI  - MiR-520b inhibits the development of glioma by directly targeting MBD2.
AB  - MicroRNAs play important roles in the process of cancer, which microRNA-520b (miR
      520b) has been reported to play critical roles in tumor progression in many types
      of cancers. However, its role in glioma remains unknown. In this study, we found
      that miR-520b could inhibit growth and progression in glioma by targeting methyl
      CpG-binding domain 2 (MBD2). First, we analyzed the expression of miR-520b in
      different glioma grades and different cell lines (U87, U251 and astrocyte). Then
      we assessed the effect of miR-520b on glucose metabolism, invasion, angiogenesis
      and chemosensitivity in U87 and U251 cells. By using an online database, miR-520b
      was found to directly bind to the 3'-untranslated regions (3'-UTR) of MBD2 and
      reduce its expression at the protein level, which further inhibits the
      development of glioma. MBD2 was also found to be over-expressed in human glioma
      tissues and in U87 and U251 cells and its level was inversely correlated with
      that of miR-520b. Furthermore, restoration of MBD2 partially rescued the miR-520b
      induced inhibitory effect on glucose metabolism, invasion, angiogenesis and
      chemosensitivity in glioma cells. In summary, to date, this is the first study to
      demonstrate that miR-520b functions as a tumor suppressor in glioma by directly
      targeting MBD2, suggesting that MBD2 may be a potential therapeutic target for
      glioma.

PMID- 28744403
TI  - Genomic alterations in advanced gastric cancer endoscopic biopsy samples using
      targeted next-generation sequencing.
AB  - Gastric cancer (GC) remains the second tumor caused death threat worldwide, and
      personalized medicine for GC is far from expectation. Finding novel, recurrently
      mutated genes through next-generation sequencing (NGS) is a powerful and
      productive approach. However, previous genomic data for GC are based on surgical
      resected samples while a large proportion of advanced gastric cancer (AGC)
      patients have already missed the chance for operation. The aim of this study is
      to assess frequent genomic alteration in AGC via biopsy samples. Here we
      performed targeted genomic sequencing of 78 AGC patients' tumor biopsies along
      with matched lymphocyte samples based on a 118 cancer related gene panel. In
      total, we observed 301 somatic nonsynonymous genomic alterations in 92 different
      genes, as well as 37 copy number gain events among 15 different genes (fold
      change 2-12), and validated the fold changes of ERBB2 copy number gains with IHC
      and FISH test showed an accuracy of 81.8%. Previously reported driver genes for
      gastric cancer (TP53, KMT2D, KMT2B, EGFR, PIK3CA, GNAQ, and ARID1A), and several
      unreported mutations (TGFBR2, RNF213, NF1, NSD1, and LRP2) showed high non-silent
      mutation prevalence (7.7%-34.6%). When comparing intestinal-type gastric cancer
      (IGC) with diffuse-type gastric cancer (DGC), TP53 and GNAQ appear to be more
      frequently mutated in IGC (P=0.028 and P=0.023, respectively), whereas LRP2,
      BRCA2 and FGFR3 mutations are not observed in IGC, but have 12.8%, 7.7% and 7.7%
      mutation rates, respectively, in DGC patients. Patients with one or more
      mutations in adherens junction pathway (CREBBP, EP300, CDH1, CTNNB1, EGFR, MET,
      TGFBR2 and ERBB2) or TGF-beta signaling pathway (CREBBP, EP300, MYST4, KRAS and
      TGFBR2) showed significantly better overall survival (P=0.007 and P=0.014,
      respectively), consistent with The Cancer Genome Atlas (TCGA) cohort data.
      Importantly, 57 (73.1%) patients harbored at least one genomic alteration with
      potential treatments, making NGS-based drug target screening a viable option for
      AGC patients. Our study established a comprehensive genomic portrait of AGC, and
      identified several mutation signatures highly associated with clinical features,
      survival outcomes, which may be used to design future personalized treatments.

PMID- 28744404
TI  - UHRF1 promotes breast cancer progression by suppressing KLF17 expression by
      hypermethylating its promoter.
AB  - UHRF1 is an epigenetic regulator and perform pivotal functions in cell
      tumorigenesis. We found UHRF1 is increased in breast cancer and patients with
      high UHRF1 levels have poorer prognoses than those with low UHRF1 levels.
      However, the underlying mechanisms remain largely unknown. Here, we found
      overexpression UHRF1 indeed promoted cell proliferation and migration, whereas
      its downregulation had the opposite functions. In vivo, UHRF1 also accelerated
      tumor growth. Mechanistically, microarrays were performed in MDA-MB-231 sh-UHRF1
      and NC cells and KLF17, with rich CpG islands on its promoter region, finally
      caused our attention. Then, the expression of UHRF1 and KLF17 was testified
      negatively correlated in breast cancer cell lines and tissues. Additionally, the
      inhibition of cell proliferation and migration by UHRF1 depletion can be rescued
      by KLF17 silencing, suggesting KLF17 is downstream gene of UHRF1. The potential
      mechanism is that overexpression UHRF1 increased methylation of CpG nucleotides
      on KLF17 promoter, while UHRF1 silence decreased methylation. Collectively, our
      results demonstrated that increased UHRF1 can promote breast cancer cell
      proliferation and migration via silencing of KLF17 expression through CpG island
      methylation on its promoter.

PMID- 28744405
TI  - Circular RNA circ-ABCB10 promotes breast cancer proliferation and progression
      through sponging miR-1271.
AB  - Circular RNA (circRNA) is a key regulator in the development and progression of
      human cancers, however its role in breast cancer tumorigenesis is not well
      understood. The present study aims to investigate the expression profiles and
      potential modulation of circRNA on breast cancer carcinogenesis. Human circRNA
      microarray was performed to screen for abnormally expressed circRNA in breast
      cancer tissue. Results found circ-ABCB10, was significantly up-regulated in
      breast cancer tissue. And results were replicated in a larger sample size. In
      vitro, loss-of-function experiments showed circ-ABCB10 knockdown suppressed the
      proliferation and increased apoptosis of breast cancer cells. Bioinformatics
      prediction program predicted the complementary sequence within circ-ABCB10 and
      miR-1271, which was validated by luciferase reporter assay. Finally, miR-1271
      rescued the function of circ-ABCB10 on breast cancer cells, confirming the sponge
      effect of circ-ABCB10 on miR-1271. Overall, results identified a new functional
      circ-ABCB10 in breast cancer tumorigenesis, and reveal the important regulatory
      role of circ-ABCB10 through sponging miR-1271, providing a novel insight for
      breast cancer pathogenesis.

PMID- 28744406
TI  - Long noncoding RNA LeXis promotes osteosarcoma growth through upregulation of
      CTNNB1 expression.
AB  - Osteosarcoma (OS) is the most common primary bone cancer in adolescents and
      children. Long noncoding RNAs (lncRNAs) contain > 200 nucleotides and do not have
      protein-coding ability. Liver-expressed LXR-induced sequence (LeXis) is a newly
      identified functional lncRNA. However, its expression pattern, biological
      function, and molecular mechanism in OS progression are unclear. The present
      study is the first to show that LeXis expression was upregulated in OS tissues.
      Increased LeXis expression was significantly correlated with high tumor stage,
      large tumor size, and poor prognosis. Our findings highlight the oncogenic
      activity of lncRNA LeXis in OS growth. Results of functional assays showed that
      LeXis promoted OS growth both in vitro and in vivo. Mechanistic investigation
      showed that LeXis directly interacted with miR-199a and suppressed its
      expression. Moreover, LeXis increased CTNNB1 expression by functioning as a ceRNA
      of CTNNB1 against miR-199a. These findings may have important implications for
      developing novel therapeutic strategies for OS.

PMID- 28744407
TI  - The use of natural products to target cancer stem cells.
AB  - The cancer stem cell hypothesis has been used to explain many cancer
      complications resulting in poor patient outcomes including induced drug
      resistance, metastases to distant organs, and tumor recurrence. While the
      validity of the cancer stem cell model continues to be the cause of much
      scientific debate, a number of putative cancer stem cell markers have been
      identified making studies concerning the targeting of cancer stem cells possible.
      In this review, a number of identifying properties of cancer stem cells have been
      outlined including properties contributing to the drug resistance and metastatic
      potential commonly observed in supposed cancer stem cells. Due to cancer stem
      cells' numerous survival mechanisms, the diversity of cancer stem cell markers
      between cancer types and tissues, and the prevalence of cancer stem cell markers
      among healthy stem and somatic cells, it is likely that currently utilized
      treatments will continue to fail to eradicate cancer stem cells. The successful
      treatment of cancer stem cells will rely upon the development of anti-neoplastic
      drugs capable of influencing many cellular mechanisms simultaneously in order to
      prevent the survival of this evasive subpopulation. Natural compounds represent a
      historically rich source of novel, biologically active compounds which are able
      to interact with a large number of cellular targets while limiting the painful
      side-effects commonly associated with cancer treatment. A brief review of select
      natural products that have been demonstrated to diminish the clinically
      devastating properties of cancer stem cells or to induce cancer stem cell death
      is also presented.

PMID- 28744408
TI  - The role of thiazolidinediones in hepatocellular carcinoma risk reduction: a
      population-based cohort study in Taiwan.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of
      thiazolidinediones (TZDs) on the risk of hepatocellular carcinoma (HCC)
      development among diabetes mellitus (DM) patients. METHODS: We conducted a
      population-based case-control study in Taiwan based on data from the Taiwan
      National Health Insurance Research Database. A total of 76,349 newly diagnosed DM
      patients were identified from claims between 2000 and 2010. Among diabetics,
      3,026 and 12,104 patients respectively, received or did not receive TZDs.
      Comparison frequency was matched with age, sex, and index date, excluding those
      with cancer at baseline. The incidence of HCC at the end of 2010 and the risks
      associated with the presence of hepatitis B and C infections were analyzed. The
      effect of TZDs use on the reduction of HCC risk was also assessed. RESULTS: The
      incidence of HCC was lower in the TZD cohort compared with the non-TZD cohort
      (418.3 vs. 484.6 per 100,000 person-years), with an adjusted hazard ratio (HR) of
      0.53 (95% confidence interval = 0.38-0.77) using multivariable Cox proportional
      hazard regression. In the stratified analysis, HCC risk reduction was greater for
      diabetics without the comorbidities of cirrhosis, hepatitis B, hepatitis C,
      nonalcoholic fatty liver disease, end-stage renal disease, and hyperlipidemia, in
      the TZD cohort than in the non-TZD cohort. Male sex, cirrhosis, hepatitis B, and
      hepatitis C were significant independent factors predicting HCC (HRs of 1.43,
      13.96, 2.31, and 2.15, respectively). CONCLUSIONS: This study suggests that the
      use of TZDs may reduce the risk of developing HCC among DM patients. Comorbidity
      with cirrhosis and/or hepatitis B/C infection appears to be associated with an
      extremely increased risk of developing HCC in this patient subset. These high
      risk patients should be closely monitored.

PMID- 28744409
TI  - In the Field Feasibility of a Simple Method to Check for Radioactivity in
      Commodities and in the Environment.
AB  - INTRODUCTION: Some release of radionuclides into the environment can be expected
      from the growing number of nuclear plants, either in or out of service. The
      citizen and the big organization could be both interested in simple and
      innovative methods for checking the radiological safety of their environment and
      of commodities, starting from foods. METHODS: In this work three methods to
      detect radioactivity are briefly compared  focusing on the most recent, which
      converts a smartphone into a radiation counter. RESULTS: The results of a simple
      sensitivity test are presented showing the measure of the activity of reference
      sources put at different distances from each sensor. DISCUSSION: The three
      methods are discussed in terms of availability, technology, sensitivity,
      resolution and usefulness. The reported results can be usefully transferred into
      a radiological emergency scenario and they also offer some interesting
      implication for our current everyday life, but show that the hardware of the
      tested smart-phone can detect only high levels of radioactivity. However the
      technology could be interesting to build a working detection and measurement
      chain which could start from a diffused and networked first screening before the
      final high resolution analysis.

PMID- 28744410
TI  - Pilot Testing and Implementation of a mHealth tool for Non-communicable Diseases
      in a Humanitarian Setting.
AB  - INTRODUCTION: Given the protracted nature of the crisis in Syria, national and
      international assistance agencies face immense challenges in providing for the
      needs of refugees and the host Lebanese due to the high burden of noncommunicable
      diseases (NCDs) among both populations. These are complex conditions to manage,
      and the resources for refugee care limited, having dramatic implications for
      Lebanon's health system. METHODS: A longitudinal cohort study was implemented
      from January 2015 through August 2016 to evaluate the effectiveness of treatment
      guidelines and an mHealth application on quality of care and health outcomes for
      patients in primary health care facilities in Lebanon serving Syrian refugees and
      host communities. RESULTS: Overall, reporting in clinic medical records remained
      low, however, during the mHealth phase recording of BMI and blood pressure were
      significantly greater in the mHealth application as compared to clinic medical
      records. Patient exit interviews reported a much more frequent measurement of
      weight, height, blood pressure, and blood glucose, suggesting these may be
      assessed more often than they are recorded. Satisfaction with the clinic visit
      improved significantly during implementation of the mHealth application as
      compared to both baseline and guidelines implementation in all measures. Despite
      positive changes, provider uptake of the application was low; patients indicated
      that the mHealth application was used in a minority (21.7%) of consultations.
      Provider perspectives on how the application changed patient interactions were
      mixed. DISCUSSION: Similar to previous evidence, this study further demonstrates
      the need to incorporate new interventions with existing practices and reporting
      requirements to minimize duplication of efforts and, consequently, strengthen
      provider usage. Additional research is needed to identify organizational and
      provider-side factors associated with uptake of similar applications,
      particularly in complex settings, to optimize the benefit of such tools.

PMID- 28744411
TI  - The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and
      Adrenal Suppression.
AB  - Duchenne muscular dystrophy (DMD or Duchenne) is a progressive, life-limiting
      muscle-wasting disease that requires comprehensive, multidisciplinary care. This
      care, at minimum, should include neuromuscular, respiratory, cardiac, orthopedic,
      endocrine and rehabilitative interventions that address both the primary and
      secondary manifestations of the disease. The care needs of patients evolve over
      the cdourse of the disease and as they transition from childhood into young
      adulthood. In the past two decades, life expectancy has increased significantly
      by the use of corticosteroids and enhanced clinical management. Nevertheless,
      each year, patients with Duchenne muscular dystrophy are admitted to emergency
      departments and intensive care units where medical expertise thrives, but where
      expertise in rare diseases, such as Duchenne, may not. Emergency care for
      patients with Duchenne can be as complex as the disease process itself. While any
      illness or injury may occur in a person with Duchenne, some acute scenarios are
      much more common in the context of the disease. Making decisions about the
      clinical care of a person with Duchenne who presents with an acute illness can be
      quite difficult - in part, because of the extensive use of corticosteroids, which
      can lead to adrenal suppression. The life of a person with Duchenne needing
      emergency care may therefore depend upon the ability of the clinician on duty in
      the emergency department to recognize and mitigate adrenal suppression resulting
      from corticosteroid dependence. With this in mind, and drawing from expertise and
      experience with other steroid-dependent diseases, the 'PJ Nicholoff Steroid
      Protocol' was developed. The purpose of this protocol is to provide clinicians
      information regarding the safe management of corticosteroid during emergency
      situations in patients who may have accompanying adrenal suppression. The
      protocol explains how to recognize the signs and symptoms of acute adrenal
      crisis, how to prevent it with supplemental stress doses of corticosteroids, and
      how to taper doses after emergency care in order to prevent corticosteroid
      withdrawal.

PMID- 28744412
TI  - A Rare Case of Carcinoma in the Thyroglossal Duct Cyst of an Elderly Patient.
AB  - Thyroglossal duct cysts are the most common congenital abnormalities of the neck,
      constituting about 70% of all cervical neck masses in children and 7% of the
      adult population. The occurrence of carcinoma in a thyroglossal duct cyst is very
      rare (less than 1%). Malignancy of the thyroglossal duct cyst usually presents in
      the third or fourth decade of life. We report a case of carcinoma in the
      thyroglossal duct cyst, which presented for the first time in our elderly
      patient.  A 76-year-old male presented with a 6 x 5 cm swelling in the anterior
      aspect of the neck. The swelling had been present for three months and had a
      variegated consistency. It moved with deglutition as well as with protrusion of
      the tongue. Intra-operatively, the lesion was cystic and was adherent to the
      hyoid bone. Sistrunk operation was done. The post-operative histopathology showed
      papillary carcinoma in the thyroglossal duct cyst.  The standard treatment is
      Sistrunk procedure with close follow-up of the patient. Patients with metastatic
      disease require a total thyroidectomy and in the presence of neck secondaries,
      neck dissection has to be done. The diagnosis can be missed because of the rarity
      of this condition. Carcinoma should be suspected in a thyroglossal duct cyst when
      presenting for the first time in the elderly age group.

PMID- 28744413
TI  - More Than Meets the Eye: The Contributions of John Dalrymple (1803-1852).
AB  - Having authored two major ophthalmology textbooks and honored with the eponym,
      the "Dalrymple sign," many are familiar with the works of Dr. John Dalrymple when
      it comes to the eye. However, few are aware of his other, numerous and wide
      ranging contributions to the fields of science and medicine. In this article, we
      discuss the life and work of a man dedicated to the pursuit and advancement of
      knowledge and education.

PMID- 28744414
TI  - Diagnostic Work-Up of a Giant Calcified Intracranial Aneurysm: Comparing 4D-CTA
      and Cerebral Angiogram Findings.
AB  - The risks associated with unruptured intracranial aneurysms can be neurologically
      debilitating and even fatal. Evaluation of these aneurysms is critical for
      determining what type of intervention is warranted, if at all. Cerebral
      angiography has long been the gold standard in the evaluation of intracranial
      aneurysms. However, this diagnostic modality is accompanied by several risks that
      are made clear to the patient before they consent to the procedure. These risks
      include the possibility of stroke, groin hematomas, contrast-induced anaphylaxis,
      contrast nephropathy, and catheter-associated infections. Dynamic CT angiography
      (4D-CTA) has been studied as an assessment tool for cerebral vasculopathies such
      as stroke, arteriovenous malformations, and aneurysms. It has been shown that 4D
      CTA has the advantage of being less invasive and has a shorter examination time
      than cerebral angiography. In this article, we present a rare case of a giant
      calcified aneurysm and compare the findings of a cerebral angiogram and a 4D-CTA
      study.

PMID- 28744415
TI  - A Long Survival Woman with Primary Small-Cell Carcinoma of the Gallbladder: Role
      of Chemotherapy Maintenance.
AB  - Gallbladder small-cell carcinoma (SCC) is an extremely rare cancer characterized
      by early metastases and associated with poor survival outcomes. The therapeutic
      options are limited in this indication and dedicated prospective trials are
      difficult to achieve. Maintenance chemotherapy is an evolving concept in medical
      oncology whose goal is to prolong chemotherapy-induced response. The role of
      maintenance therapy has been demonstrated especially in many cancers but the
      results remain controversial in small cell cancer. We report a case of a 49-year
      old woman admitted in our institution with biliary colic, postprandial bilious
      vomiting, right hypochondrial mass, and deteriorated general condition. Abdominal
      computed tomography (CT) revealed a mass of the gallbladder with lymphadenopathy
      in the hepatic hilum and multiple liver metastases. CT-guided biopsy was
      performed that showed small, round cells with high nuclear-to-cytoplasmic ratio,
      and frequent atypical mitosis, which is consistent with high-grade small cell
      neuroendocrine carcinoma. Tumor cells were positive for chromogranin A,
      synaptophysin, and CD56. Ki-67 shows a high proliferation rate with 90% tumor
      cell staining and the diagnosis of gallbladder SCC was confirmed. The treatment
      used a combination of carboplatin and etoposide, interrupted by the generalized
      discomfort and shortness of breath during the second course of the etoposide.
      Repeated CT scan showed a partial radiological response in the order of 35% and
      carboplatin monotherapy was maintained with good tolerance and stability of the
      disease until the 11th cure. Thrombocytopenia at 70,000 per mm3 appeared, and its
      persistence forced the cessation of this treatment. Five months later, the
      disease progressed and second-line chemotherapy by irinotecan was given weekly.
      The death occurred 18 months after initiation of medical treatment due to
      hepatocellular insufficiency. Maintenance therapy in SCC should be considered as
      a promising therapeutic option when it is well tolerated.

PMID- 28744416
TI  - Immune Reconstitution Inflammatory Syndrome Associated Thrombocytopenia in a
      Patient with Human Immunodeficiency Virus Infection: A Rare Hematological
      Manifestation.
AB  - Human immunodeficiency virus (HIV) associated thrombocytopenia was commonly
      encountered in the era prior to the advent of antiretroviral therapy (ART). With
      the widespread use of ART, its incidence has significantly declined. Immune
      reconstitution inflammatory syndrome (IRIS) is an immune dysregulation phenomenon
      that reveals itself clinically as paradoxical deterioration after the
      commencement of ART in HIV infected patients. It has a wide variety of clinical
      manifestations. However, hematologic involvement is rare. Here, we present a very
      rare case of IRIS associated thrombocytopenia. With this case we intend to create
      mindfulness of the possibility of IRIS being one of the explanations for
      thrombocytopenia.

PMID- 28744417
TI  - Acute Myocardial Infarction in Young Systemic Lupus Erythematosus Patient with
      Normal Coronary Arteries.
AB  - A 34-year-old female with a past medical history of systemic lupus erythematosus
      (SLE) and a deep venous thrombosis experienced substernal chest pain for 24
      hours. Her physical exam was remarkable for brown macular rash over the face. Her
      initial electrocardiogram showed ST depression in lead V3-V6 along with an
      elevated troponin I level of 1.23 ng/dl (normal 0.0-0.4) that increased to 2.33
      ng/dl in a four-hour duration. Cardiac catheterization revealed mild 10-20% focal
      plaque in the mid left anterior descending artery and otherwise normal coronary
      arteries. Laboratory data revealed an erythrocyte sedimentation rate of 98
      mm/hour (normal 1-20), C-reactive protein of 25 mg/L (normal 0.0-2.9), and
      positive antinuclear antibody. In the absence of a significant coronary
      atherosclerosis along with elevated inflammatory markers, inflammation of
      coronary microcirculation was considered as an underlying pathophysiology of
      myocardial infarction. The patient was started on immunosuppression therapy with
      hydroxychloroquine and prednisone. Her chest pain improved and she was discharged
      in a stable condition. The patient remained stable and symptom-free over a follow
      up period of nine months.

PMID- 28744418
TI  - Lumbar Spinal Candida Glabrata Treated Without Surgical Intervention: A Case
      Report.
AB  - Candida glabrata is a low virulent commensal fungal organism that, rarely, can
      cause osteomyelitis. Diagnosis of such an infection is often difficult as the
      case typically presents with an insidious onset of back pain and minimally
      elevated biomarkers of inflammation. Furthermore, it is difficult to eradicate
      and often resistant to common antifungals.  A 61-year-old man presented with an
      eight-month history of persistent low back pain which had unsuccessfully been
      managed by his primary care physician. He had a past surgical history of gastric
      by-pass complicated by adhesions, ulceration, and perforation with an infection
      of Candida glabrata that had been treated with intravenous micafungin.
      Radiological examination showed degenerative changes with suspicion of
      osteomyelitis and a computerized tomography (CT)-guided biopsy provided tissue
      samples with subsequent positive cultures for Candida glabrata. The patient was
      admitted for fungal osteomyelitis with Candida glabrata, treated with intravenous
      micafungin, and his infection was resolved after six months. At two-year follow
      up his back pain has been resolved and no infection was present. In a patient
      with osteoarticular pain and a previous history of candidal infection with
      possible candidemia, one should maintain suspicion for fungal osteomyelitis.

PMID- 28744419
TI  - Role of Speckle Tracking Echocardiography in Dilated Cardiomyopathy: A Review.
AB  - Dilated cardiomyopathy (DCM) is an important cause of the heart failure. Timely
      diagnosis and optimal management decrease morbidity and mortality in heart
      failure patients. Although transthoracic echocardiography is used as the
      diagnostic test of choice in these patients, new modalities like speckle tracking
      echocardiography (STE) have promising results in diagnosing these patients in the
      earlier course of the disease. Advancements in cardiac imaging are expected as
      more clinical studies on the role of STE in different cardiac diseases that
      emerge. In this review article, we will discuss the basics of STE and its role in
      diagnosing DCM.

PMID- 28744420
TI  - A Rare Case of Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma Transforming
      into Diffuse Large B-Cell Lymphoma.
AB  - Mucosa-associated lymphoid tissue lymphoma (MALToma) is a low grade B-cell
      lymphoma that develops from the lungs, intestinal tract, salivary gland, and
      other organs and is included under extranodal marginal zone lymphoma. When a
      primary pulmonary MALToma develops from bronchus-associated lymphoid tissue
      (BALT), it is called BALT lymphoma (BALToma). The etiology of MALToma is not
      clear; however, an association between chronic inflammatory conditions and
      BALToma has been observed. Transformation of MALToma to high grade lymphoma is
      very rare. We experienced a case of MALToma that had developed from the lungs in
      a patient who was undergoing treatment for latent tuberculosis and rapidly
      transformed into high grade B-cell lymphoma.

PMID- 28744421
TI  - Polyparaneoplastic Manifestations of Malignant Thymoma: A Unique Case of
      Myasthenia, Autoimmune Hepatitis, Pure Red Cell Aplasia, and Keratoconjunctivitis
      Sicca.
AB  - Thymomas are relatively uncommon malignancies of the anterior mediastinum and
      present with four distinct histological types based on the specific epithelial to
      lymphocyte ratio: spindle cell, epithelial predominant, lymphocyte predominant,
      or mixed. Each histologic type of thymoma has a propensity for local invasion and
      metastasis and can have a wide variety of paraneoplastic manifestations,
      myasthenia being the most common. We present a unique case of a 34-year-old
      African-American female who initially presented with a history of profound
      weakness with repetitive motion, shortness of breath, horizontal nystagmus,
      persistent anemia, keratoconjunctivitis sicca, and what was initially thought to
      be azithromycin-induced hepatitis. Upon left anterior thoracotomy with biopsy of
      the mediastinal mass, pathology yielded a lymphocyte-predominant (B1), Masaoka
      stage IVA invasive thymoma with pericardial extension. This case illustrates the
      clinical significance of considering a multitude of extrathymic paraneoplastic
      manifestations, each with a unique physiological mechanism.

PMID- 28744422
TI  - Rectal Carcinoma: Demographics and Clinicopathological Features from Pakistani
      Population Perspective.
AB  - BACKGROUND: Colorectal carcinoma is ranked as the second most common cancer
      diagnosis in females and third in males. It is the third leading cause of cancer
      related deaths worldwide. Disease burden has been attributed to a myriad of
      factors comprising genetic, environmental, and dietary factors. Rectal cancer has
      been shown to demonstrate variance according to the geographical location.
      METHODS: A retrospective review of 477 rectal cancer patients treated at Shaukat
      Khanum Memorial Cancer Hospital & Research Centre from 2006 to 2014 was
      performed. Demographic and clinicopathological features were compared between the
      two age groups (<=40 or >40 years). These included sex, ethnicity, family history
      of cancer, the location of tumor, clinical staging, histopathological type, and
      response to chemoradiation. Chi-square was used to compare the frequencies
      between the two age groups. p-value < 0.05 was taken as significant. RESULTS:
      Mean age of the study group was 44.62 +/- 16.11 years. 43.8% were <=40 years of
      age, and 70.2% were male. 50.3% patients belong to Punjab province, 287 (60.2%)
      had lower rectal cancer, family history of cancer was present in 82 (17.2%)
      patients. 432 (90.5%) patients had T1/T2 disease and 296 (62.1%) had N2 disease.
      Metastatic disease at presentation was observed in 37 (7.8%). Progressive disease
      was found in 90 (18%) patients. CONCLUSION: High frequency of young onset rectal
      cancers and the lack of family history emphasize the need of indigenous
      strategies and national awareness of this disease for an early identification of
      these patients.

PMID- 28744423
TI  - A Successful Therapeutic Challenge: Local Reirradiation of Breast Cancer with a
      Single Dose of 18 Gy Intraoperative Radiation Therapy (IORT).
AB  - After standard treatment of primary breast cancer, local relapse can develop in a
      previously irradiated region. The decision to refer a patient for a second
      radiotherapy must be thoroughly evaluated due to the increased risk of side
      effects. We report a case of a 43-year-old Caucasian female with a history of
      left breast lumpectomy and radiation treatment in 1990 for an invasive ductal
      carcinoma who presented with a locoregional recurrence 19 years later. After
      careful evaluation, the patient has undergone a second breast-conserving surgery
      and successful reirradiation with 18 Gy single dose of intraoperative radiation
      therapy (IORT).

PMID- 28744424
TI  - Single-molecule fluorescence imaging of RalGDS on cell surfaces during signal
      transduction from Ras to Ral.
AB  - RalGDS is one of the Ras effectors and functions as a guanine nucleotide exchange
      factor for the small G-protein, Ral, which regulates membrane trafficking and
      cytoskeletal remodeling. The translocation of RalGDS from the cytoplasm to the
      plasma membrane is required for Ral activation. In this study, to understand the
      mechanism of Ras-Ral signaling we performed a single-molecule fluorescence
      analysis of RalGDS and its functional domains (RBD and REMCDC) on the plasma
      membranes of living HeLa cells. Increased molecular density of RalGDS and RBD,
      but not REMCDC, was observed on the plasma membrane after EGF stimulation of the
      cells to induce Ras activation, suggesting that the translocation of RalGDS
      involves an interaction between the GTP-bound active form of Ras and the RBD of
      RalGDS. Whereas the RBD played an important role in increasing the association
      rate constant between RalGDS and the plasma membrane, the REMCDC domain affected
      the dissociation rate constant from the membrane, which decreased after Ras
      activation or the hyperexpression of Ral. The Y64 residue of Ras and clusters of
      RalGDS molecules were involved in this reduction. From these findings, we infer
      that Ras activation not merely increases the cell-surface density of RalGDS, but
      actively stimulates the RalGDS-Ral interaction through a structural change in
      RalGDS and/or the accumulation of Ral, as well as the GTP-Ras/RalGDS clusters, to
      induce the full activation of Ral.

PMID- 28744425
TI  - Domain-to-domain coupling in voltage-sensing phosphatase.
AB  - Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and
      a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2
      domains, is structurally similar to the tumor suppressor phosphatase PTEN, and
      catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage
      sensor is connected to the phosphatase through a short linker region, and
      phosphatase activity is induced upon membrane depolarization. Although the
      detailed molecular characteristics of the voltage sensor domain and the enzyme
      region have been revealed, little is known how these two regions are coupled. In
      addition, it is important to know whether mechanism for coupling between the
      voltage sensor domain and downstream effector function is shared among other
      voltage sensor domain-containing proteins. Recent studies in which specific amino
      acid sites were genetically labeled using a fluorescent unnatural amino acid have
      enabled detection of the local structural changes in the cytoplasmic region of
      Ciona intestinalis VSP that occur with a change in membrane potential. The
      results of those studies provide novel insight into how the enzyme activity of
      the cytoplasmic region of VSP is regulated by the voltage sensor domain.

PMID- 28744426
TI  - Role of stereospecific nature of germinants in Bacillus megaterium spores
      germination.
AB  - The present study was undertaken with the objective to assess the effect of
      distinct stereoisomeric forms of nutrient germinants (selected sugars and amino
      acids) on the process of germination onset in dormant spores of Bacillus
      megaterium MTCC 2949. In this respect, epimers of glucose and enantiomers of
      alanine were employed in current work. When supplemented with these
      stereoisomers, spores were found germinated only with d-glucose and d-mannose
      among epimers of glucose and only with l-alanine among enantiomers of alanine.
      Interestingly, germination in spores was observed to negligible extent with d
      galactose and d-alanine. These findings were obtained on the basis of four type
      of germination assays, namely reduction in absorbance measured at 600 nm (<=5 to
      >=30%), refractility examination (phase bright and dark), esterase assay
      [fluorescence units 0.455-94.62 (*103)] and fluorescent staining (fluorescent/non
      fluorescent signals). Understanding of spores germination process and efficacy of
      different forms of germinants to trigger germination is of immense importance. It
      aids in development of sensing and sterilization indicating tools employing
      chiefly spores as biorecognition elements and in uncovering the mechanism of
      diseases, food contamination and spoilages resulting from the germination of
      spores. The findings of current work support the possibility to explore such
      germination mechanism by significantly giving the clue for potential existence of
      stereospecific receptor sites on the surface of B. megaterium spores. Perhaps,
      these sites can specifically differentiate and recognize stereoisomerically
      diverse forms of germinants for induction of germination.

PMID- 28744427
TI  - A sequential pretreatment of lignocelluloses in bamboo biomass to fermentable
      sugars by acid/enzymatic hydrolysis.
AB  - A sequential pretreatment method for hydrolyzing rigid hemicelluloses and
      cellulose content in the bamboo biomass was investigated in this study. The
      effects of different parameters, such as nature of biomass, type of acid, acid
      and biomass concentration, were studied. Under the optimum condition of 5% (v/v)
      HCl-treated biomass and biomass concentration (8%, w/v), the maximum yield of
      sugar (619 mg/g of biomass) was obtained. The enzymatic hydrolysis parameter
      conditions were further optimized by response surface methodology-based central
      composite method. According to the results, the highest yield of sugar (515 mg/g
      of biomass) was obtained at hydrolysis temperature 50  degrees C, biomass
      concentration 8.9%, w/v, enzyme concentration (199.8 mg/g of biomass) and time 60
      h, respectively. The effects of untreated, pretreated and enzymatically
      hydrolyzed biomass structure and complexity were investigated by field emission
      scanning electron microscopy and X-ray diffraction techniques.

PMID- 28744428
TI  - Bioengineering of Dioscorea nipponica with rhizospheric Proteus spp. for enhanced
      tuber size and diosgenin content.
AB  - Rhizobacterial production of plant hormones, ACC deaminase, fixation of nitrogen,
      solubilization of phosphate and antimicrobial metabolites play very important
      role in the health and growth of plants. Hence exploration of plant probiotic
      prospectives of promising rhizobacterial isolates from biodiversity rich areas
      can have enormous applications to engineer both the biomass and active
      ingredients of plants. In the present study, rhizospheric Proteus spp. R6 and R60
      isolated from Pseudarthria viscida and Glycosmis arborea were analyzed for tuber
      and diosgenin enhancement effects in Dioscorea nipponica under field conditions
      for 1 year. Among the two Proteus spp. selected, both were positive for ACC
      deaminase, siderophore, nitrogen fixation, IAA and ammonia production. However,
      the isolate R6 was found to have additional phosphate solubilizing activity.
      Quantitative analysis of IAA by HPTLC showed its maximum production by Proteus
      sp. R60 (714.47 +/- 8.7 ug/mL) followed by Proteus sp. R6 (588.06 +/- 7.0 ug/mL).
      The tubers formed from the Proteus sp. R6 treated samples were identified to have
      significant enhancement in size, root number and diosgenin content when compared
      to control. Interestingly, HPLC analysis has confirmed twofold higher diosgenin
      content in Proteus sp. R6 treated samples than control during 1 year period of
      its field growth. The obtained results are of great importance as it involved the
      utilization of rhizospheric bacteria to improve tuber size which suggests its
      potential use in developing cost-effective, eco-friendly and multifunctional
      biofertilizer.

PMID- 28744429
TI  - Efficient biodegradation of acephate by Pseudomonas pseudoalcaligenes PS-5 in the
      presence and absence of heavy metal ions [Cu(II) and Fe(III)], and humic acid.
AB  - The present study was intended to investigate the biodegradation of acephate in
      aqueous media in the presence and in the absence of metal ions [Fe(III) and
      Cu(II)], and humic acid (HA). Biodegradations were performed using Pseudomonas
      pseudoalcaligenes PS-5 (PS-5) isolated from the heavy metal polluted site.
      Biodegradations were monitored by UV-Visible, FTIR, and electron spray ionization
      mass spectrometry (ESI-MS) analyses. ESI-MS analysis revealed that PS-5 degraded
      acephate to two metabolites showing intense ions at mass-to-charge ratios (m/z)
      62 and 97. The observed kinetic was the pseudo-first order, and half-life periods
      (t1/2) were 2.79 d-1 (of PS-5 + acephate), 3.45 d-1 [of PS-5 + acephate +
      Fe(III)], 3.16 d-1 [of PS-5 + acephate + Cu(II)], and 5.54 d-1 (of PS-5 +
      acephate + HA). A significant decrease in degradation rate of acephate was
      noticed in the presence of HA, and the same was confirmed by UV-Visible and TGA
      analyses. Strong aggregation behavior of acephate with humic acid in aqueous
      media was the major cause behind the slow degradation rate of acephate . New
      results on acephate metabolism by strain PS-5 in the presence and in the absence
      of metal ions [Fe(III) and Cu(II)] and humic acid were obtained. Results
      confirmed that Pseudomonas pseudoalcaligenes strain PS-5 was capable of
      mineralization of the acephate without formation of toxic metabolite
      methamidophos. More significantly, the Pseudomonas pseudoalcaligenes strain PS-5
      could be useful as potential biological agents in effective bioremediation
      campaign for multi-polluted environments.

PMID- 28744430
TI  - Data collection using open access technology in multicentre operational research
      involving patient interviews.
AB  - Conducting multicentre operational research is challenging due to issues related
      to the logistics of travel, training, supervision, monitoring and troubleshooting
      support. This is even more burdensome in resource-constrained settings and if the
      research includes patient interviews. In this article, we describe an innovative
      model that uses open access tools such as Dropbox, TeamViewer and CamScanner for
      efficient, quality-assured data collection in an ongoing multicentre operational
      research study involving record review and patient interviews. The tools used for
      data collection have been shared for adaptation and use by other researchers.

PMID- 28744431
TI  - What was the effect of the West African Ebola outbreak on health programme
      performance, and did programmes recover?

PMID- 28744432
TI  - The influence of the Ebola outbreak on presumptive and active tuberculosis in
      Bombali District, Sierra Leone.
AB  - Setting: Bombali District, rural Sierra Leone. Objective: To compare the number
      of patients with presumptive tuberculosis (TB), the number of patients registered
      with TB (including testing for the human immunodeficiency virus [HIV] and
      initiation on antiretroviral therapy [ART]) and treatment outcomes during the pre
      Ebola, Ebola and post-Ebola disease outbreak periods between 2013 and 2016.
      Design: This was a cross-sectional study and retrospective cohort analysis of
      treatment outcomes. Results: The mean monthly number of patients with presumptive
      TB before, during and post-Ebola was respectively 169, 145 and 210. The mean
      monthly number of registered TB cases was respectively 57, 57 and 96. Smear
      positive TB was the most frequent type of TB, at 75%, 66% and 77%. The proportion
      of TB patients tested for HIV was 82% pre-Ebola, 74% Ebola and 99% post-Ebola.
      The proportion of HIV-positive patients with TB initiated on ART was respectively
      46%, 85% and 100%. Treatment success among TB patients was 71% in the pre-Ebola
      period and 89% in the Ebola period (P < 0.001). Conclusion: During the Ebola
      outbreak, there were decreases in the number of presumptive TB patients and in
      the proportions of patients diagnosed with smear-positive TB and tested for HIV.
      The initiation of ART in HIV-infected TB patients and treatment outcomes remained
      acceptable. Pre-emptive actions are needed to maintain adequate control
      activities in future outbreaks.

PMID- 28744433
TI  - The Ebola outbreak: effects on HIV reporting, testing and care in Bonthe
      district, rural Sierra Leone.
AB  - Setting: All public health facilities in Bonthe District, rural Sierra Leone.
      Objective: To compare, in the periods before and during the Ebola virus disease
      outbreak, 1) the submission and completeness of monthly human immunodeficiency
      virus (HIV) reports, and 2) the uptake of HIV testing and care for pregnant women
      and the general population. Design: A cross-sectional study using routine
      programme data. Results: Of the 627 HIV reports expected in each period, 406
      (65%) were submitted in the pre-Ebola period and 376 (60%) during the Ebola
      outbreak (P = 0.08), of which respectively 318 (78%) and 335 (89%) had complete
      information (P < 0.001). In the pre-Ebola period, 5012 pregnant women underwent
      testing for HIV, of whom 25 were HIV-positive, compared to 4254 during the Ebola
      period, of whom 21 were HIV-positive (P < 0.001). Of those who were HIV-positive,
      respectively 14 (56%) and 21 (100%) received antiretroviral prophylaxis or
      antiretroviral therapy (ART) (P < 0.001). In the general population, 5770 persons
      underwent HIV testing pre-Ebola vs. 3095 in the Ebola period (P < 0.001); of
      those who tested positive for HIV, respectively 62% (33/53) and 81% (33/41) were
      started on ART (P = 0.06). Conclusion: There was suboptimal reporting on
      HIV/acquired immune-deficiency disease syndrome activities before and during the
      Ebola virus disease outbreak. HIV testing decreased during the Ebola outbreak,
      while the uptake of prevention of mother-to-child transmission and ART increased.
      Pre-emptive actions are needed to maintain the levels of HIV testing in any
      future outbreak.

PMID- 28744434
TI  - Non-communicable diseases in the Western Area District, Sierra Leone, before and
      during the Ebola outbreak.
AB  - Setting: Twenty-seven peripheral health units, five secondary hospitals and one
      tertiary hospital, Western Area District, Sierra Leone. Objectives: To describe
      reporting systems, monthly attendances and facility-based patterns of six non
      communicable diseases (NCDs) in the pre-Ebola and Ebola virus disease outbreak
      periods. Design: A cross-sectional study using programme data. Results: Reporting
      was 89% complete on the six selected NCDs pre-Ebola and 86% during the Ebola
      outbreak (P < 0.01). Overall, marked declining trends in NCDs were reported
      during the Ebola period, with a monthly mean of 342 cases pre-Ebola and 164
      during the Ebola outbreak. The monthly mean number of cases per disease in the
      pre-Ebola and Ebola outbreak periods was respectively 228 vs. 85 for
      hypertension, 43 vs. 27 for cardiovascular diseases, 36 vs. 18 for diabetes and
      25 vs. 29 for peptic ulcer disease; this last condition increased during the
      outbreak. There were higher proportions of NCDs among females during the Ebola
      outbreak compared with the pre-Ebola period. Except for peptic ulcer disease, the
      number of patients with NCDs declined by 25% in peripheral health units, 91% in
      the secondary hospitals and 70% in the tertiary hospital between the pre-Ebola
      and the Ebola outbreak periods. Conclusion: Comprehensive reporting of NCDs was
      suboptimal, and declined during the Ebola epidemic. There were decreases in
      reported attendances for NCDs between the pre-Ebola and the Ebola outbreak
      periods, which were even more marked in the hospitals. This study has important
      policy implications.

PMID- 28744435
TI  - Management of malaria in children with fever in rural Sierra Leone in relation to
      the 2014-2015 Ebola outbreak.
AB  - Setting: Sixty-eight primary health facilities, Koinadugu District, rural Sierra
      Leone. Objectives: Sierra Leone, a country with one of the highest burdens of
      malaria, was severely affected by the 2014-2015 Ebola virus disease outbreak. In
      under-five children, we compared trends in the completeness of malaria reports
      sent to the district office during the pre-Ebola, Ebola and post-Ebola periods,
      including the number of children with reported fever, malaria diagnostic testing
      performed and treatment for malaria initiated with artemisinin-based combination
      therapy (ACT). Design: A cross-sectional study. Results: Of 1904 expected malaria
      reports, 1289 (68%) were received. Completeness of reporting was 61% pre-Ebola,
      increased to 88% during the outbreak and dropped to 44% post-Ebola (P = 0.003).
      Total malaria testing (n = 105 558) exceeded the number of fever cases (n = 105
      320). Pre-Ebola, 75% (n = 43 245) of all reported fever cases received malaria
      treatment, dropping to 34% (n = 50 453) during the Ebola outbreak. Of 36 804
      confirmed malaria cases during Ebola, 17 438 (47%) were treated, significantly
      fewer than in the pre-Ebola period (96%, P < 0.001). Of the fever cases, 95% in
      both the pre- and post-Ebola periods received ACT, a rate that increased to 99%
      during the Ebola outbreak. Conclusion: Pre-existing gaps in malaria reporting
      worsened after the Ebola outbreak. Reassuringly, malaria testing matched fever
      cases, although only half of all confirmed cases received treatment during the
      outbreak, possibly explained by outbreak-related operational difficulties. These
      findings could be useful to guide health systems strengthening and recovery.

PMID- 28744436
TI  - Increase in acute malnutrition in children following the 2014-2015 Ebola outbreak
      in rural Sierra Leone.
AB  - Setting: All health facility and community malnutrition screening programmes in
      Tonkolili, a rural Ebola-affected district in Sierra Leone. Objectives: Before
      the Ebola disease outbreak, Sierra Leone had set a goal to reduce the prevalence
      of severe acute malnutrition (SAM) in children aged <5 years to <0.2%. We
      compared the number of children screened, diagnosed and treated for malnutrition
      before, during and after the outbreak (2013-2016). Design: This was a
      retrospective cross-sectional study. Results: Health facility screening declined
      from 16 805 children per month pre-outbreak to 13 510 during the outbreak (P =
      0.02), and returned to pre-outbreak levels after the outbreak. Community-based
      screening remained stable during the outbreak, and increased by 30% post-outbreak
      (P < 0.001). The proportion diagnosed with moderate acute malnutrition using mid
      upper arm circumference increased from respectively 3.6% and 5.1% pre-outbreak in
      the community and health facilities to 8.2% and 7.9% post-outbreak (P < 0.001, P
      = 0.003). The proportion of children diagnosed with SAM using a weight-for-age
      ratio at health facilities increased from 1.5% pre-outbreak to 3.5% post-outbreak
      (P = 0.003). On average, for every four children diagnosed with SAM per month,
      one child completed SAM treatment. Conclusion: After a decline in screening
      during the Ebola outbreak, diagnoses of acute malnutrition increased post
      outbreak. Nutrition programmes need to be strengthened to pre-empt such effects
      in the event of future Ebola outbreaks.

PMID- 28744437
TI  - Paediatric care in relation to the 2014-2015 Ebola outbreak and general reporting
      of deaths in Sierra Leone.
AB  - Setting: All peripheral health units countrywide in Sierra Leone and one hospital
      in Port Loko. Objectives: Sierra Leone was severely affected by the 2014-2015
      Ebola outbreak, whose impact on paediatric care and mortality reports merits
      assessment. We sought to compare the periods before, during and after the Ebola
      outbreak, the countrywide trend in morbidities in children aged < 5 years and
      exit outcomes in one district hospital (Port Loko). During the Ebola outbreak
      period, gaps in district death reporting within the routine Health Management
      Information System (HMIS) were compared with the Safe and Dignified Burials (SDB)
      database in Port Loko. Design: This was a retrospective records analysis.
      Results: The average number of monthly consultations during the Ebola outbreak
      period declined by 27% for malaria and acute respiratory infections and 38% for
      watery diarrhoea, and did not recover to the pre-Ebola levels. For measles, there
      was an 80% increase during Ebola, which multiplied by 6.5-fold post-Ebola. The
      number of unfavourable hospital exit outcomes was 52/397 (13%) during Ebola,
      which was higher than pre-Ebola (47/496, 9%, P = 0.04). Of 6565 deaths reported
      in the Port Loko SDB database, only 2219 (34%) appeared in the HMIS, a reporting
      deficit of 66%. Conclusion: The Ebola disease outbreak was associated with
      reduced utilisation of health services, and appears to have triggered a measles
      epidemic. Almost 70% of deaths were missed by the HMIS during the Ebola outbreak
      period. These findings could guide health system responses in future outbreaks.

PMID- 28744438
TI  - Life goes on: the resilience of maternal primary care during the Ebola outbreak
      in rural Sierra Leone.
AB  - Setting: All 100 health facilities providing maternal services in Moyamba, Sierra
      Leone, a rural district that experienced a smaller Ebola outbreak than other
      areas. Objective: To compare trends in antenatal care (the first and fourth visit
      [ANC1 and ANC4]), delivery, and postnatal care (PNC1) service utilisation before,
      during and after the Ebola outbreak (2014-2016). Design: Cross-sectional study
      using secondary programme data. Results: A total of 211 Ebola cases occurred in
      Moyamba District. The mean number of monthly ANC visits remained stable over
      time, except for the subset of care provided via outreach visits where, compared
      with before the outbreak (n = 390), ANC1 visits declined during (n = 331, P =
      0.002) and after the outbreak (n = 342, P = 0.03). Most (>97%) deliveries
      occurred in health facilities, assisted by maternal and child health aides
      (>80%). During the outbreak, the mean number of community-based deliveries per
      month declined from 31 to 21 (P = 0.03), and the mean number of deliveries
      performed by midwives increased from 49 to 78 (P < 0.001) compared with before
      the outbreak. Before, during and after Ebola, there was no significant change in
      the mean number of live births (respectively n = 1134, n = 1110, n = 1162),
      maternal PNC1 (respectively n = 1110, n = 1105, n = 1165) or neonatal PNC1
      (respectively n = 1028, n = 1050, n = 1085). Conclusion: In a rural district less
      affected by Ebola transmission than other areas, utilisation of maternal primary
      care remained robust, despite the outbreak.

PMID- 28744439
TI  - The Ebola outbreak and staffing in public health facilities in rural Sierra
      Leone: who is left to do the job?
AB  - Setting: The 82 public health facilities of rural Kailahun District, Sierra
      Leone. Objective: The 2014-2015 Ebola virus disease outbreak in Sierra Leone led
      the Ministry of Health and Sanitation and stakeholders to set minimum standards
      of staffing (medical/non-medical) for a basic package of essential health
      services (BPEHS). No district-level information exists on staffing levels in
      relation to the Ebola outbreak. We examined the staffing levels before the Ebola
      outbreak, during the last month of the outbreak and 4 months after the outbreak,
      as well as Ebola-related deaths among health care workers (HCWs). Design: This
      was a retrospective cross-sectional study. Results: Of 805 recommended medical
      staff (the minimum requirement for 82 health facilities), there were deficits of
      539 (67%) pre-Ebola, 528 (65%) during the Ebola outbreak and 501 (62%) post
      Ebola, hovering at staff shortages of >50% at all levels of health facilities. Of
      the 569 requisite non-medical staff, the gap remained consistent, at 92%, in the
      three time periods. Of the 1374 overall HCWs recommended by the BPEHS, the
      current staff shortage is 1026 (75%). Of 321 facility-based HCWs present during
      Ebola, there were 15 (14 medical and one non-medical staff) Ebola-related and
      three non-Ebola related deaths among HCWs. Conclusion: The post-Ebola health
      related human resource deficit is alarmingly high, with very few staff available
      to work. We call for urgent political will, resources and international
      collaboration to address this situation.

PMID- 28744440
TI  - Ebola and community health worker services in Kenema District, Sierra Leone:
      please mind the gap!
AB  - Setting: All community health workers (CHWs) in rural Kenema District, Sierra
      Leone. Objective: CHW programmes provide basic health services to fill gaps in
      human health resources. We compared trends in the reporting and management of
      childhood malaria, diarrhoea and pneumonia by CHWs before, during and after the
      Ebola outbreak (2014-2016). Design: Retrospective cross-sectional study using
      programme data. Results: CHW reporting increased from 59% pre-outbreak to 95%
      during the outbreak (P < 0.001), and was sustained at 98% post-outbreak. CHWs
      stopped using rapid diagnostic tests for malaria mid-outbreak, and their use had
      not resumed post-outbreak. The average monthly number of presumptive treatments
      for malaria increased from 2931 pre-outbreak to 5013 during and 5331 post
      outbreak (P < 0.001). The average number of monthly treatments for diarrhoea and
      pneumonia decreased from respectively 1063 and 511 pre-outbreak to 547 and 352
      during the outbreak (P = 0.01 and P = 0.04). Post-outbreak pneumonia treatments
      increased (mean 1126 compared to pre-outbreak, P = 0.003), and treatments for
      diarrhoea returned to pre-outbreak levels (P = 0.2). Conclusion: The CHW
      programme demonstrated vulnerability, but also resilience, during and in the
      early period after the Ebola outbreak. Investment in CHWs is required to
      strengthen the health care system, as they can cover pre-existing gaps in
      facility-based health care and those created by outbreaks.

PMID- 28744441
TI  - Influence of Ebola on tuberculosis case finding and treatment outcomes in
      Liberia.
AB  - Setting: National Leprosy and Tuberculosis (TB) Control Programme, Liberia.
      Objectives: To assess TB case finding, including human immunodeficiency virus
      (HIV) associated interventions and treatment outcomes, before (January 2013-March
      2014), during (April 2014-June 2015) and after (July-December 2015) the Ebola
      virus disease outbreak. Design: A cross-sectional study and retrospective cohort
      analysis of outcomes. Results: The mean quarterly numbers of individuals with
      presumptive TB and the proportion diagnosed as smear-positive were: pre-Ebola (n
      = 7032, 12%), Ebola (n = 6147, 10%) and post-Ebola (n = 6795, 8%). For all forms
      of TB, stratified by category and age group, there was a non-significant decrease
      in the number of cases from the pre-Ebola to the Ebola and post-Ebola periods.
      There were significant decreases in numbers of cases with smear-positive
      pulmonary TB (PTB) from the pre-Ebola period (n = 855), to the Ebola (n = 640, P
      < 0.001) and post-Ebola (n = 568, P < 0.001) periods. The proportions of patients
      tested for HIV, found to be HIV-positive and started on antiretroviral therapy
      decreased as follows: pre-Ebola (respectively 72%, 15% and 34%), Ebola (69%, 14%
      and 30%) and post-Ebola (68%, 12% and 26%). Treatment success rates among TB
      patients were: 80% pre-Ebola, 69% Ebola (P < 0.001) and 73% post-Ebola (P <
      0.001). Loss to follow-up was the main contributing adverse outcome. Conclusion:
      The principal negative effects of Ebola were the significant decreases in
      diagnoses of smear-positive PTB, the declines in HIV testing and antiretroviral
      therapy uptake and poor treatment success. Ways to prevent these adverse effects
      from recurring in the event of another Ebola outbreak need to be found.

PMID- 28744442
TI  - Did the 2014 Ebola outbreak in Liberia affect HIV testing, linkage to care and
      ART initiation?
AB  - Setting: Health facilities providing human immunodeficiency virus (HIV) testing,
      care and treatment in Liberia. Objective: To evaluate individuals aged ?15 years
      who were tested, diagnosed and enrolled into HIV care before (2013), during
      (2014) and after the Ebola outbreak (2015). Design: A cross-sectional descriptive
      study. Results: A median of 6930 individuals aged ?15 years per county were
      tested for HIV before the Ebola outbreak; this number declined by 35% (2444/6930)
      during the outbreak. HIV positivity remained similar before (7028/207 314, 3.4%)
      and during the outbreak (4146/121 592, 3.5%). During Ebola, HIV testing declined
      more in highly affected counties (68 035/127 468, 47%) than in counties that were
      less affected (16 444/23 955, 31%, P < 0.001). Compared to the pre-Ebola period,
      HIV testing in less-affected counties recovered more quickly during the post
      outbreak period, with a 19% increase in testing, while medium and highly affected
      counties remained at respectively 38% and 48% below pre-outbreak levels.
      Enrolment for HIV care increased during and after the outbreak compared to the
      pre-Ebola period. Conclusion: HIV testing and diagnosis were significantly
      limited during the Ebola outbreak, with the most severe effects occurring in
      highly affected counties. However, enrolment for HIV care and treatment were
      resilient throughout the outbreak. Pro-active measures are needed to sustain HIV
      testing rates in future epidemics.

PMID- 28744443
TI  - Knockdown and recovery of malaria diagnosis and treatment in Liberia during and
      after the 2014 Ebola outbreak.
AB  - Setting: The malaria-endemic country of Liberia, before, during and after the
      2014 Ebola outbreak. Objective: To describe the consequences of the Ebola
      outbreak on Liberia's National Malaria Programme and its post-Ebola recovery.
      Design: A retrospective cross-sectional study using routine countrywide programme
      data. Results: Malaria caseloads decreased by 47% during the Ebola outbreak and
      by 11% after, compared to the pre-Ebola period. In those counties most affected
      by Ebola, a caseload reduction of >20% was sustained for 12 consecutive months,
      while this lasted for only 4 consecutive months in the counties least affected by
      Ebola. Linear regression of monthly proportions of confirmed malaria cases-as a
      proxy indicator of programme performance-over the pre- and post-Ebola periods
      indicated that the malaria programme could require 26 months after the end of the
      acute phase of the Ebola outbreak to recover to pre-Ebola levels. Conclusions:
      The differential persistence of reduced caseloads in the least- and most-affected
      counties, all of which experienced similar emergency measures, suggest that
      factors other than Ebola-related security measures played a key role in the
      programme's reduced performance. Clear guidance on when to abandon the emergency
      measures after an outbreak may be needed to ensure faster recovery of malaria
      programme performance.

PMID- 28744444
TI  - Did the Ebola outbreak disrupt immunisation services? A case study from Liberia.
AB  - Setting: All health facilities providing routine immunisation services in
      Liberia. Objective: To compare the number of routine facility-based and outreach
      immunisations and measles cases before, during and after the Ebola outbreak.
      Design: A descriptive cross-sectional study. Results: Immunisation coverage for
      fully immunised children before the Ebola outbreak was 73%. Immunisation coverage
      for all antigens declined by half compared to baseline during the outbreak. These
      findings were similar in facility-based and outreach immunisations. During the
      outbreak, the proportion of fully immunised children dropped by respectively 58%,
      33% and 39% in the most, moderately and least Ebola-affected counties.
      Immunisation rate of recovery in the post-Ebola period was respectively 82%, 21%
      and 9% in the most, moderately and least affected counties compared to the Ebola
      outbreak period. Outreach immunisation recovered slowly compared to facility
      based immunisation. The mean number of measles cases reported per month was 12
      pre-Ebola, 16 Ebola and 60 post-Ebola. Conclusion: This study provides insights
      into the possible impact of an Ebola outbreak on countrywide immunisation. The
      outbreak weakened a struggling national immunisation programme, and post-outbreak
      recovery took significant time, which likely contributed to the measles epidemic.
      Recommendations for the improvement of immunisation services that could limit
      further preventable epidemics in Liberia and similar contexts at risk for Ebola
      are provided.

PMID- 28744445
TI  - Effects of the 2014 Ebola outbreak on antenatal care and delivery outcomes in
      Liberia: a nationwide analysis.
AB  - Setting: All health facilities, public and private, in Liberia, West Africa.
      Objectives: To determine access to antenatal care (ANC), deliveries and their
      outcomes before, during and after the 2014-2015 Ebola outbreak. Design: This was
      a descriptive cross-sectional study. Result: During the Ebola outbreak in
      Liberia, overall monthly reporting from health facilities plunged by 43%. Access
      to ANC declined by 50% and reported deliveries fell by one third during the
      outbreak. Reported deliveries by skilled attendants and Caesarian section
      declined by respectively 32% and 60%. Facility-based deliveries dropped by 35%
      and reported community deliveries fell by 47%. There was an overall decline in
      reported stillbirths, maternal and neonatal deaths, by 50%, during the outbreak.
      ANC, reported deliveries and related outcomes returned to pre-outbreak levels
      within one year following the outbreak. Conclusion: The Liberian health system
      was considerably weakened during the Ebola outbreak and had difficulties
      providing basic maternal health services. In the light of the major reporting
      gaps during the Ebola period, and the reduced use of health facilities for
      maternal care, these findings highlight the need for measures to avoid such
      disruptions during future outbreaks.

PMID- 28744446
TI  - Infection prevention and control in health facilities in post-Ebola Liberia:
      don't forget the private sector!
AB  - Setting: Recognising the importance of infection prevention and control (IPC), a
      minimum standards tool (MST) was developed in Liberia to guide the safe (re-)
      opening and provision of care in health facilities. Objectives: To analyse the
      implementation of specific IPC measures after the 2014 Ebola virus outbreak
      between June 2015 and May 2016, and to compare the relative improvements in IPC
      between the public and private sectors. Design: A retrospective comparative
      cohort study. Results: We evaluated 723 (94%) of the 769 health facilities in
      Liberia. Of these, 437 (60%) were public and 286 (40%) were private. There was an
      overall improvement in the MST scores from a median of 13 to 14 out of a maximum
      possible score of 16. While improvements were observed in all aspects of IPC in
      both public and private health facilities, IPC implementation was systematically
      higher in public facilities. Conclusions: We demonstrate the feasibility of
      monitoring IPC implementation using the MST checklist in post-Ebola Liberia. Our
      study shows that improvements were made in key aspects of IPC after 1 year of
      evaluations and tailored recommendations. We also highlight the need to increase
      the focus on the private sector to achieve further improvements in IPC.

PMID- 28744447
TI  - Performance-based financing contributes to the resilience of health services
      affected by the Liberian Ebola outbreak.
AB  - Setting: The Liberian counties of Bong, with performance-based financing (PBF)
      for all 36 public primary-care facilities, and Margibi, with no PBF for its 24
      public primary-care facilities. Objective: To compare whether specific maternal
      and child health indicators changed in the two counties during the pre-Ebola
      (2013), Ebola (2014) and post-Ebola (2015) disease outbreak periods from July to
      September each year. Design: This was a cross-sectional study. Results: For
      pregnant women, the numbers of antenatal visits, intermittent preventive malaria
      treatments, human immunodeficiency virus (HIV) tests and facility-based births
      with skilled attendants all fell during the Ebola period, with decreases being
      significantly more marked in Margibi County. Apart from HIV testing, which
      remained low in both counties, these indicators increased in the post-Ebola
      period, with increases significantly more marked in Bong than in Margibi. The
      number of childhood immunisations decreased significantly in Bong in the Ebola
      period compared with the pre-Ebola period, but increased to above pre-Ebola
      levels in the post-Ebola period. There were markedly larger decreases in
      childhood immunisations in Margibi County during the Ebola period, which remained
      significantly lower in the post-Ebola period compared with Bong County.
      Conclusion: In a PBF-supported county, selected maternal and childhood health
      indicators showed less deterioration during Ebola and better recovery post-Ebola
      than in a non-PBF-supported county.

PMID- 28744448
TI  - Angiogenic Gene Signature Derived from Subtype Specific Cell Models Segregate
      Proneural and Mesenchymal Glioblastoma.
AB  - Intertumoral molecular heterogeneity in glioblastoma identifies four major
      subtypes based on expression of molecular markers. Among them, the two clinically
      interrelated subtypes, proneural and mesenchymal, are the most aggressive with
      proneural liable for conversion to mesenchymal upon therapy. Using two patient
      derived novel primary cell culture models (MTA10 and KW10), we developed a
      minimal but unique four-gene signature comprising genes vascular endothelial
      growth factor A (VEGF-A), vascular endothelial growth factor B (VEGF-B) and
      angiopoietin 1 (ANG1), angiopoietin 2 (ANG2) that effectively segregated the
      proneural (MTA10) and mesenchymal (KW10) glioblastoma subtypes. The cell culture
      preclassified as mesenchymal showed elevated expression of genes VEGF-A, VEGF-B
      and ANG1, ANG2 as compared to the other cell culture model that mimicked the
      proneural subtype. The differentially expressed genes in these two cell culture
      models were confirmed by us using TCGA and Verhaak databases and we refer to it
      as a minimal multigene signature (MMS). We validated this MMS on human
      glioblastoma tissue sections with the use of immunohistochemistry on
      preclassified (YKL-40 high or mesenchymal glioblastoma and OLIG2 high or
      proneural glioblastoma) tumor samples (n = 30). MMS segregated mesenchymal and
      proneural subtypes with 83% efficiency using a simple histopathology scoring
      approach (p = 0.008 for ANG2 and p = 0.01 for ANG1). Furthermore, MMS expression
      negatively correlated with patient survival. Importantly, MMS staining
      demonstrated spatiotemporal heterogeneity within each subclass, adding further
      complexity to subtype identification in glioblastoma. In conclusion, we report a
      novel and simple sequencing-independent histopathology-based biomarker signature
      comprising genes VEGF-A, VEGF-B and ANG1, ANG2 for subtyping of proneural and
      mesenchymal glioblastoma.

PMID- 28744450
TI  - Editorial: Molecular Pathogenesis of Pneumococcus.

PMID- 28744449
TI  - Emerging Tick-Borne Viruses in the Twenty-First Century.
AB  - Ticks, as a group, are second only to mosquitoes as vectors of pathogens to
      humans and are the primary vector for pathogens of livestock, companion animals,
      and wildlife. The role of ticks in the transmission of viruses has been known for
      over 100 years and yet new pathogenic viruses are still being detected and known
      viruses are continually spreading to new geographic locations. Partly as a result
      of their novelty, tick-virus interactions are at an early stage in understanding.
      For some viruses, even the principal tick-vector is not known. It is likely that
      tick-borne viruses will continue to emerge and challenge public and veterinary
      health long into the twenty-first century. However, studies focusing on tick
      saliva, a critical component of tick feeding, virus transmission, and a target
      for control of ticks and tick-borne diseases, point toward solutions to emerging
      viruses. The aim of this review is to describe some currently emerging tick-borne
      diseases, their causative viruses, and to discuss research on virus-tick
      interactions. Through focus on this area, future protein targets for intervention
      and vaccine development may be identified.

PMID- 28744451
TI  - Lipopolysaccharide Upregulated Intestinal Epithelial Cell Expression of Fn14 and
      Activation of Fn14 Signaling Amplify Intestinal TLR4-Mediated Inflammation.
AB  - TLR4 in intestinal epithelial cells has been shown both inflammatory and
      homeostatic roles following binding of its cognate ligand lipopolysaccharide
      (LPS). TWEAK-Fn14 axis plays an important role in pathologies caused by excessive
      or abnormal inflammatory responses. This study aimed to evaluate potential cross
      talk between TLR4 and TWEAK/Fn14 system in porcine small intestinal epithelial
      cells. Our in vivo results showed that, compared with the age-matched normal
      control piglets, increased expression of Fn14 in epithelium and decreased TWEAK
      expression in lamina propria were detected in the small intestinal of piglets
      stimulated with LPS. Consistent with this finding, treatment with LPS increased
      the expression of Fn14 and TLR4 while decreased TWEAK expression in porcine small
      intestinal epithelial cell lines SIEC02. Interestingly, modulating Fn14
      activation using agonistic anti-Fn14 decreased TLR4-mediated TNF-alpha production
      by SIEC02. In addition, pretreatment of LPS-stimulated SIEC02 with recombinant
      TWEAK protein suppresses the expression of Fn14 and TNF-alpha and inhibits the
      negative impact of LPS on the tight junctional protein occludin expression. In
      conclusion, this study demonstrates that the TWEAK-independent Fn14 activation
      augments TLR4-mediated inflammatory responses in the intestine of piglets.
      Furthermore, the TWEAK-dependent suppression of Fn14 signaling may play a role in
      intestinal homeostasis.

PMID- 28744452
TI  - Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on
      Alzheimer's Disease (AD): Detection of Lipopolysaccharide (LPS) in AD
      Hippocampus.
AB  - Although the potential contribution of the human gastrointestinal (GI) tract
      microbiome to human health, aging, and disease is becoming increasingly
      acknowledged, the molecular mechanics and signaling pathways of just how this is
      accomplished is not well-understood. Major bacterial species of the GI tract,
      such as the abundant Gram-negative bacilli Bacteroides fragilis (B. fragilis) and
      Escherichia coli (E. coli), secrete a remarkably complex array of pro
      inflammatory neurotoxins which, when released from the confines of the healthy GI
      tract, are pathogenic and highly detrimental to the homeostatic function of
      neurons in the central nervous system (CNS). For the first time here we report
      the presence of bacterial lipopolysaccharide (LPS) in brain lysates from the
      hippocampus and superior temporal lobe neocortex of Alzheimer's disease (AD)
      brains. Mean LPS levels varied from two-fold increases in the neocortex to three
      fold increases in the hippocampus, AD over age-matched controls, however some
      samples from advanced AD hippocampal cases exhibited up to a 26-fold increase in
      LPS over age-matched controls. This "Perspectives" paper will further highlight
      some very recent research on GI tract microbiome signaling to the human CNS, and
      will update current findings that implicate GI tract microbiome-derived LPS as an
      important internal contributor to inflammatory degeneration in the CNS.

PMID- 28744454
TI  - Staff Perspectives on a Tablet-Based Intervention to Increase HIV Testing in a
      High Volume, Urban Emergency Department.
AB  - Emergency departments (EDs) frequently serve people who have limited, if any,
      additional interactions with health care, yet many ED patients are not offered
      HIV testing, and those who are frequently decline. ED staff (n = 13) at a high
      volume urban ED (technicians, nurses, physicians, and administrators) were
      interviewed to elicit their perspectives on the feasibility and acceptability of
      a tablet-based intervention designed to increase HIV test rates among patients
      who initially decline testing. Content-based thematic analysis of semi-structured
      interviews indicated overall support for interventions to increase HIV testing,
      but a lack of available staff resources emerged as a potential barrier to
      widespread implementation. Also, some ED staff questioned whether it was
      appropriate to shift responsibility for public health services, such as HIV
      testing, to the ED instead of a primary care setting. Although tablet-based
      interventions have been shown effective in high volume ED settings and can
      potentially increase HIV test rates among hard-to-reach populations, additional
      effort is now required to better integrate this type of intervention into
      existing workflows.

PMID- 28744453
TI  - Targeted therapy and personalized medicine in hepatocellular carcinoma: drug
      resistance, mechanisms, and treatment strategies.
AB  - Hepatocellular carcinoma (HCC) is characterized by a growing number of new cases
      diagnosed each year that is nearly equal to the number of deaths from this
      cancer. In a majority of the cases, HCC is associated with the underlying chronic
      liver disease, and it is diagnosed in advanced stage of disease when curative
      treatment options are not applicable. Sorafenib is a treatment of choice for
      patients with performance status 1 or 2 and/or macrovascular invasion or
      extrahepatic spread, and regorafenib is the only systemic treatment found to
      provide survival benefit in HCC patients progressing on sorafenib treatment.
      Other drugs tested in different trials failed to demonstrate any benefit.
      Disappointing results of numerous trials testing the efficacy of various drugs
      indicate that HCC has low sensitivity to chemotherapy that is in great part
      caused by multidrug resistance. Immunotherapy for HCC is a new challenging
      treatment option and involves immune checkpoint inhibitors/antibody-based therapy
      and peptide-based vaccines. Another challenging approach is microRNA-based
      therapy that involves two strategies. The first aims to inhibit oncogenic miRNAs
      by using miRNA antagonists and the second strategy is miRNA replacement, which
      involves the reintroduction of a tumor-suppressor miRNA mimetic to restore a loss
      of function.

PMID- 28744455
TI  - Genetic Control of Ascorbic Acid Biosynthesis and Recycling in Horticultural
      Crops.
AB  - Ascorbic acid (AsA) is an essential compound present in almost all living
      organisms that has important functions in several aspects of plant growth and
      development, hormone signaling, as well as stress defense networks. In recent
      years, the genetic regulation of AsA metabolic pathways has received much
      attention due to its beneficial role in human diet. Despite the great variability
      within species, genotypes, tissues and developmental stages, AsA accumulation is
      considered to be controlled by the fine orchestration of net biosynthesis,
      recycling, degradation/oxidation, and/or intercellular and intracellular
      transport. To date, several structural genes from the AsA metabolic pathways and
      transcription factors are considered to significantly affect AsA in plant
      tissues, either at the level of activity, transcription or translation via
      feedback inhibition. Yet, all the emerging studies support the notion that the
      steps proceeding through GDP-L-galactose phosphorylase and to a lesser extent
      through GDP-D-mannose-3,5-epimerase are control points in governing AsA pool size
      in several species. In this mini review, we discuss the current consensus of the
      genetic regulation of AsA biosynthesis and recycling, with a focus on
      horticultural crops. The aspects of AsA degradation and transport are not
      discussed herein. Novel insights of how this multifaceted trait is regulated are
      critical to prioritize candidate genes for follow-up studies toward improving the
      nutritional value of fruits and vegetables.

PMID- 28744457
TI  - Homeostatic Eosinophils: Characteristics and Functions.
AB  - Eosinophils are typically considered to be specialized effector cells that are
      recruited to the tissues as a result of T helper type 2 (Th2) cell responses
      associated with helminth infections or allergic diseases such as asthma. Once at
      the site of injury, eosinophils release their cytotoxic granule proteins as well
      as preformed cytokines and lipid mediators, contributing to parasite destruction
      but also to exacerbation of inflammation and tissue damage. Accumulating evidence
      indicates that, besides their roles in Th2 responses, eosinophils also regulate
      homeostatic processes at steady state, thereby challenging the exclusive paradigm
      of the eosinophil as a destructive and inflammatory cell. Indeed, under baseline
      conditions, eosinophils rapidly leave the bloodstream to enter tissues, mainly
      the gastrointestinal tract, lungs, adipose tissue, thymus, uterus, and mammary
      glands, where they regulate a variety of important biological functions, such as
      immunoregulation, control of glucose homeostasis, protection against obesity,
      regulation of mammary gland development, and preparation of the uterus for
      pregnancy. This article provides an overview of the characteristics and functions
      of these homeostatic eosinophils.

PMID- 28744458
TI  - Probing Long Non-coding RNA-Protein Interactions.
AB  - Non-coding RNA sequences outnumber the protein-coding genes in the human genome,
      however our knowledge of their functions is still limited. RNA-binding proteins
      follow the transcripts, including non-coding RNAs, throughout their life,
      regulating not only maturation, nuclear export, stability and eventually
      translation, but also RNA functions. Therefore, development of sophisticated
      methods to study RNA-protein interactions are key to the systematic
      characterization of lncRNAs. Although mostly applicable to RNA-protein
      interactions in general, many approaches, especially the computational ones, need
      adjustment to be adapted to the length and complexity of lncRNA transcripts. Here
      we critically review all the wet lab and computational methods to study lncRNA
      protein interactions and their potential to clarify the dark side of the genome.

PMID- 28744456
TI  - New Challenges to Study Heterogeneity in Cancer Redox Metabolism.
AB  - Reactive oxygen species (ROS) are important pathophysiological molecules involved
      in vital cellular processes. They are extremely harmful at high concentrations
      because they promote the generation of radicals and the oxidation of lipids,
      proteins, and nucleic acids, which can result in apoptosis. An imbalance of ROS
      and a disturbance of redox homeostasis are now recognized as a hallmark of
      complex diseases. Considering that ROS levels are significantly increased in
      cancer cells due to mitochondrial dysfunction, ROS metabolism has been targeted
      for the development of efficient treatment strategies, and antioxidants are used
      as potential chemotherapeutic drugs. However, initial ROS-focused clinical trials
      in which antioxidants were supplemented to patients provided inconsistent
      results, i.e., improved treatment or increased malignancy. These different
      outcomes may result from the highly heterogeneous redox responses of tumors in
      different patients. Hence, population-based treatment strategies are unsuitable
      and patient-tailored therapeutic approaches are required for the effective
      treatment of patients. Moreover, due to the crosstalk between ROS, reducing
      equivalents [e.g., NAD(P)H] and central metabolism, which is heterogeneous in
      cancer, finding the best therapeutic target requires the consideration of system
      wide approaches that are capable of capturing the complex alterations observed in
      all of the associated pathways. Systems biology and engineering approaches may be
      employed to overcome these challenges, together with tools developed in
      personalized medicine. However, ROS- and redox-based therapies have yet to be
      addressed by these methodologies in the context of disease treatment. Here, we
      review the role of ROS and their coupled redox partners in tumorigenesis.
      Specifically, we highlight some of the challenges in understanding the role of
      hydrogen peroxide (H2O2), one of the most important ROS in pathophysiology in the
      progression of cancer. We also discuss its interplay with antioxidant defenses,
      such as the coupled peroxiredoxin/thioredoxin and glutathione/glutathione
      peroxidase systems, and its reducing equivalent metabolism. Finally, we highlight
      the need for system-level and patient-tailored approaches to clarify the roles of
      these systems and identify therapeutic targets through the use of the tools
      developed in personalized medicine.

PMID- 28744459
TI  - Utilization of Mechanistic Enzymology to Evaluate the Significance of ADP Binding
      to Human Lon Protease.
AB  - Lon, also known as Protease La, is one of the simplest ATP-dependent proteases.
      It is a homooligomeric enzyme comprised of an ATPase domain and a proteolytic
      domain in each enzyme subunit. Despite sharing about 40% sequence identity, human
      and Escherichia coli Lon proteases utilize a highly conserved ATPase domain found
      in the AAA+ family to catalyze ATP hydrolysis, which is needed to activate
      protein degradation. In this study, we utilized mechanistic enzymology techniques
      to show that despite comparable kcat and Km parameters found in the ATPase
      activity, human and E. coli Lon exhibit significantly different susceptibility to
      ADP inhibition. Due to the low affinity of human Lon for ADP, the conformational
      changes in human Lon generated from the ATPase cycle are also different. The
      relatively low affinity of human Lon for ADP cannot be accounted for by
      reversibility in ATP hydrolysis, as a positional isotope exchange experiment
      demonstrated both E. coli Lon and human Lon catalyzed ATP hydrolysis
      irreversibly. A limited tryptic digestion study however indicated that human and
      E. coli Lon bind to ADP differently. Taken together, the findings reported in
      this research article suggest that human Lon is not regulated by a substrate
      promoted ADP/ATP exchange mechanism as found in the bacterial enzyme homolog. The
      drastic difference in structural changes associated with ADP interaction with the
      two protease homologs offer potential for selective inhibitor design and
      development through targeting the ATPase sites. In addition to revealing unique
      mechanistic differences that distinguish human vs. bacterial Lon, this article
      underscores the benefit of mechanistic enzymology in deciphering the
      physiological mechanism of action of Lon proteases and perhaps other closely
      related ATP-dependent proteases in the future.

PMID- 28744460
TI  - Protein Function Prediction Using Deep Restricted Boltzmann Machines.
AB  - Accurately annotating biological functions of proteins is one of the key tasks in
      the postgenome era. Many machine learning based methods have been applied to
      predict functional annotations of proteins, but this task is rarely solved by
      deep learning techniques. Deep learning techniques recently have been
      successfully applied to a wide range of problems, such as video, images, and
      nature language processing. Inspired by these successful applications, we
      investigate deep restricted Boltzmann machines (DRBM), a representative deep
      learning technique, to predict the missing functional annotations of partially
      annotated proteins. Experimental results on Homo sapiens, Saccharomyces
      cerevisiae, Mus musculus, and Drosophila show that DRBM achieves better
      performance than other related methods across different evaluation metrics, and
      it also runs faster than these comparing methods.

PMID- 28744461
TI  - Integrating Genome-Wide Association and eQTLs Studies Identifies the Genes and
      Gene Sets Associated with Diabetes.
AB  - AIM: To identify novel candidate genes and gene sets for diabetes. METHODS: We
      performed an integrative analysis of genome-wide association studies (GWAS) and
      expression quantitative trait loci (eQTLs) data for diabetes. Summary data was
      driven from a large-scale GWAS of diabetes, totally involving 58,070 individuals.
      eQTLs dataset included 923,021 cis-eQTL for 14,329 genes and 4,732 trans-eQTL for
      2,612 genes. Integrative analysis of GWAS and eQTLs data was conducted by summary
      data-based Mendelian randomization (SMR). To identify the gene sets associated
      with diabetes, the SMR single gene analysis results were further subjected to
      gene set enrichment analysis (GSEA). A total of 13,311 annotated gene sets were
      analyzed in this study. RESULTS: SMR analysis identified 6 genes significantly
      associated with fasting glucose, such as C11ORF10 (p value = 6.04 * 10-8), MRPL33
      (p value = 1.24 * 10-7), and FADS1 (p value = 2.39 * 10-7). Gene set analysis
      identified HUANG_FOXA2_TARGETS_UP (false discovery rate = 0.047) associated with
      fasting glucose. CONCLUSION: Our study provides novel clues for clarifying the
      genetic mechanism of diabetes. This study also illustrated the good performance
      of SMR approach and extended it to gene set association analysis for complex
      diseases.

PMID- 28744462
TI  - Prevalence and Genetic Characterization of Cryptosporidium Infection in Java
      Sparrows (Lonchura oryzivora) in Northern China.
AB  - Cryptosporidiosis is a cosmopolitan parasitosis that affects a wide range of
      hosts including birds. As information concerning Cryptosporidium in birds is
      limited, the present study examined the prevalence and genotypes of
      Cryptosporidium in Java sparrows in Beijing and Shangqiu, northern China. Three
      hundred and fifty fecal samples were collected from Java sparrows (Lonchura
      oryzivora, 225 white Java sparrows and 125 gray Java sparrows) in Beijing and
      Shangqiu in October 2015, and the samples were examined by PCR amplification of
      the small subunit ribosomal RNA (SSU rRNA) gene. The overall Cryptosporidium
      prevalence is 13.42% (47/350), with 16.44% (37/225) in white Java sparrows and
      8.00% (10/125) in gray Java sparrows. Cryptosporidium prevalence was 9.82%
      (16/163) in Java sparrows from Beijing and 16.58% (31/187) in Java sparrows from
      Shangqiu. The prevalence of Cryptosporidium in females and males was 40.63%
      (26/64) and 7.34% (21/286), respectively. The Cryptosporidium prevalence in Java
      sparrows of different ages varied from 10.47% to 16.33%. Sequence analysis of the
      SSU rRNA gene revealed that all the samples represented C. baileyi. This is the
      first report of Cryptosporidium in gray Java sparrows in China, which extend the
      host range for C. baileyi. These results provide baseline information for further
      studies of molecular epidemiology and control of Cryptosporidium infection in
      poultry in China.

PMID- 28744463
TI  - A Measure of Suffering in relation to Anxiety and Quality of Life in IBS
      Patients: Preliminary Results.
AB  - Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder with a
      severe impact on quality of life (QoL). We explored the relationship of a visual
      measure of suffering, the PRISM-RII, with quality of life (QoL) and anxiety
      measures in IBS patients. Participants were 44 IBS patients who completed several
      questionnaires and kept a symptom diary for two weeks. The measures used were
      PRISM-RII (self-illness separation (SIS); illness perception measure (IPM)); IBS
      36 (IBS health related QoL); SF-36 (physical and mental health related QoL);
      State-Trait Anxiety Inventory (STAI-T); Visceral Sensitivity Index (VSI; GI
      specific anxiety); and a symptom diary. SIS was negatively correlated to VSI,
      while IPM was negatively correlated to SIS and the physical component of SF-36
      and positively to VSI and symptom severity. We found significant differences
      between participants who perceive their illness as small and those who perceive
      it as medium in SIS, symptom severity, VSI, and the mental component of SF-36.
      Participants, who perceived their illness as small, represented their illness as
      more distant, showed lower average symptom severity, and had lower GI-specific
      anxiety and higher QoL. The results indicate that IPM and SIS can be useful in
      discriminating patients with more prominent psychological difficulties and QoL
      impairment.

PMID- 28744464
TI  - Method of Improved Fuzzy Contrast Combined Adaptive Threshold in NSCT for Medical
      Image Enhancement.
AB  - Noises and artifacts are introduced to medical images due to acquisition
      techniques and systems. This interference leads to low contrast and distortion in
      images, which not only impacts the effectiveness of the medical image but also
      seriously affects the clinical diagnoses. This paper proposes an algorithm for
      medical image enhancement based on the nonsubsampled contourlet transform (NSCT),
      which combines adaptive threshold and an improved fuzzy set. First, the original
      image is decomposed into the NSCT domain with a low-frequency subband and several
      high-frequency subbands. Then, a linear transformation is adopted for the
      coefficients of the low-frequency component. An adaptive threshold method is used
      for the removal of high-frequency image noise. Finally, the improved fuzzy set is
      used to enhance the global contrast and the Laplace operator is used to enhance
      the details of the medical images. Experiments and simulation results show that
      the proposed method is superior to existing methods of image noise removal,
      improves the contrast of the image significantly, and obtains a better visual
      effect.

PMID- 28744465
TI  - Role of Vascular Endothelial Cells in Disseminated Intravascular Coagulation
      Induced by Seawater Immersion in a Rat Trauma Model.
AB  - Trauma complicated by seawater immersion is a complex pathophysiological process
      with higher mortality than trauma occurring on land. This study investigated the
      role of vascular endothelial cells (VECs) in trauma development in a seawater
      environment. An open abdominal injury rat model was used. The rat core
      temperatures in the seawater (SW, 22 degrees C) group and normal sodium (NS, 22
      degrees C) group declined equivalently. No rats died within 12 hours in the
      control and NS groups. However, the median lethal time of the rats in the SW
      group was only 260 minutes. Among the 84 genes involved in rat VEC biology, the
      genes exhibiting the high expression changes (84.62%, 11/13) on a qPCR array were
      associated with thrombin activity. The plasma activated partial thromboplastin
      time and fibrinogen and vWF levels decreased, whereas the prothrombin time and
      TFPI levels increased, indicating intrinsic and extrinsic coagulation pathway
      activation and inhibition, respectively. The plasma plasminogen, FDP, and D-dimer
      levels were elevated after 2 hours, and those of uPA, tPA, and PAI-1 exhibited
      marked changes, indicating disseminated intravascular coagulation (DIC).
      Additionally, multiorgan haemorrhagia was observed. It indicated that seawater
      immersion during trauma may increase DIC, elevating mortality. VECs injury might
      play an essential role in this process.

PMID- 28744466
TI  - CMIP Promotes Proliferation and Metastasis in Human Glioma.
AB  - Glioma is one of the most common primary malignant brain tumors and the outcomes
      are generally poor. The intrinsic mechanisms involved in glioma development and
      progression remain unclear. Further studies are urgent and necessary. In this
      study, we have proven that CMIP (C-Maf-inducing protein) promotes cell
      proliferation and metastasis in A172 cells through knockdown of CMIP and in U251
      cells through overexpression of CMIP by using MTT assay, cell colony formation
      assay, cell migration assay, and cell invasion assay. Furthermore, we discovered
      that CMIP upregulates MDM2, which is involved in the promoting role of CMIP in
      human glioma cells. For clinical study, 99 glioma tissues and 59 normal tissues
      were analyzed. CMIP expression was higher in glioma tissues than in normal
      tissues. In glioma tissues, CMIP is found to correlate positively with tumor
      grade but no significant correlation is found with patients' age, gender, or
      Karnofsky performance score (KPS). Moreover, CMIP also correlates with low
      relapse-free survival (RFS) rate and overall survival (OS) rate in glioma
      patients. Therefore, CMIP is oncogenic and could be a potential target for human
      glioma diagnosis and therapy.

PMID- 28744467
TI  - Are There Modifiable Risk Factors to Improve AKI?
AB  - Acute kidney injury (AKI) is a common critical syndrome, with high morbidity and
      mortality. Patients with AKI typically have an adverse prognosis, from incident
      chronic kidney disease (CKD), progression to end-stage renal disease (ESRD),
      subsequent cardiovascular disease, and ultimately death. However, there is
      currently no effective therapy for AKI. Early detection of risk factors for AKI
      may offer a good approach to prevention or early intervention. Traditional risk
      factors include extreme age, many common comorbid diseases, such as preexisting
      CKD, some specific exposures, such as sepsis, and exposure to some nephrotoxic
      agents. Recently, several novel risk factors for AKI, such as hyperuricemia,
      hypoalbuminemia, obesity, anemia, and hyperglycemia, have been identified. The
      underlying mechanisms between these nontraditional risk factors and AKI and
      whether their correction can reduce AKI occurrence remain to be clarified. This
      review describes the current epidemiology of AKI, summarizes its outcome,
      outlines the traditional risk profile, and finally highlights some recently
      identified novel risk factors.

PMID- 28744468
TI  - DrugECs: An Ensemble System with Feature Subspaces for Accurate Drug-Target
      Interaction Prediction.
AB  - BACKGROUND: Drug-target interaction is key in drug discovery, especially in the
      design of new lead compound. However, the work to find a new lead compound for a
      specific target is complicated and hard, and it always leads to many mistakes.
      Therefore computational techniques are commonly adopted in drug design, which can
      save time and costs to a significant extent. RESULTS: To address the issue, a new
      prediction system is proposed in this work to identify drug-target interaction.
      First, drug-target pairs are encoded with a fragment technique and the software
      "PaDEL-Descriptor." The fragment technique is for encoding target proteins, which
      divides each protein sequence into several fragments in order and encodes each
      fragment with several physiochemical properties of amino acids. The software
      "PaDEL-Descriptor" creates encoding vectors for drug molecules. Second, the
      dataset of drug-target pairs is resampled and several overlapped subsets are
      obtained, which are then input into kNN (k-Nearest Neighbor) classifier to build
      an ensemble system. CONCLUSION: Experimental results on the drug-target dataset
      showed that our method performs better and runs faster than the state-of-the-art
      predictors.

PMID- 28744469
TI  - The Oxidative Stress Response in Elite Water Polo Players: Effects of Genetic
      Background.
AB  - Acute exercise is known to induce oxidative stress. Here we assessed the effects
      of gene polymorphisms SOD2 A16V, CAT -844 G>A, and GPx-1 rs1800668 C>T on
      oxidative stress markers in 28 elite water polo male players prior to and after a
      routinely programmed friendly match. The mean plasma concentrations of
      derivatives of reactive oxygen metabolites (dROMs), as well as lactic
      dehydrogenase (LDH) activity, creatine kinase (CK) activity, CK-MB, and
      myoglobin, were significantly increased after exercise, while blood antioxidant
      potential (BAP) and total free thiols were significantly decreased, compared with
      those measured before exercise. Advanced oxidation protein products (AOPP) were
      also increased after exercise but not significantly. We observed that water polo
      players having either AV16 or VV16 SOD genotype exhibited a significant increase
      of postexercise AOPP, LDH, CK, and myoglobin plasma levels in comparison with
      wild-type athletes. Water polo players having either CAT -844 GA or GPx1 CT
      genotype showed a significant increase of postexercise dROMs plasma levels and,
      respectively, GPx and CAT enzyme activities in comparison with wild-type
      subjects. These preliminary results suggest that the screening for gene variants
      of antioxidant enzymes could be useful to assess individual susceptibility to
      oxidative stress and muscle damage in water polo players.

PMID- 28744470
TI  - Ethnobotany of Indigenous Saraguros: Medicinal Plants Used by Community Healers
      "Hampiyachakkuna" in the San Lucas Parish, Southern Ecuador.
AB  - This paper reports the results of an ethnobotanical survey on the use of
      medicinal plants by community healers "Hampiyachakkuna" in the San Lucas Parish,
      province of Loja, Ecuador. A particular ethnic group, the indigenous Saraguros,
      inhabits this region. This study reports 183 plant species used in 75 different
      curative therapies by the Saraguro healers.

PMID- 28744471
TI  - Morphological Analysis of Bronchial Arteries and Variants with Computed
      Tomography Angiography.
AB  - The aim of our study was to determine the prevalence of anatomical variants of
      bronchial arteries using computed tomographic angiography in a population of
      northeastern Mexico. An observational, transversal, descriptive, comparative,
      retrospective study was performed using 139 imaging studies of Mexican patients
      in which we evaluated the following parameters from the left and right bronchial
      arteries: artery origin, branching pattern, arterial ostium, vertebral level of
      origin, diameter, and mediastinal trajectory. The anatomies of the bronchial
      arteries were similar in both genders, except distribution for vertebral origin
      level (p  0.006) and the diameter (p  0.013). Left and right arteries were
      similar, except for the mediastinal trajectory in reference to the esophagus (p <
      0.001) as well as the arterial diameter (p < 0.001) and lumen diameter.

PMID- 28744472
TI  - Decreased Cardiovascular Risk after Roux-en-Y Gastric Bypass Surgery in Chinese
      Diabetic Patients with Obesity.
AB  - BACKGROUND: The influence of bariatric surgery on cardiovascular risks in Chinese
      diabetic patients remains unclear. Here, we aimed to explore the impact of Roux
      en-Y gastric bypass surgery (RYGB) on cardiovascular risks in Chinese diabetic
      patients with obesity. METHODS: Twenty Chinese patients with T2DM and obesity
      undergoing RYGB surgery were included in this study. Cardiovascular risk factors
      were measured before and 18 months after surgery. A 10-year cardiovascular risk
      was calculated by the UKPDS risk engine. Linear regression analysis was performed
      on CHD risk, stroke risk, and baseline metabolic parameters. RESULTS: The
      complete remission rate of diabetes was 90% after RYGB surgery, with significant
      improvements in blood pressure, BMI, glucose, and lipid metabolism (P < 0.05).
      The 10-year cardiovascular risk of coronary heart disease reduced from 13.05% to
      3.81% (P = 0.001) and the 10-year risk of stroke reduced from 19.66% to 14.22% (P
      = 0.002). In subgroup analysis, Chinese diabetic patients who were women, <45
      years old, with BMI < 35 kg/m2, and DM duration > 5 years, using noninsulin
      therapy presented more obvious improvements in the 10-year cardiovascular risk
      after RYGB surgery. WHR, age, LDL-C, and HbA1c were the most important factors
      influencing CHD or stroke risk after RYGB surgery (P < 0.01). CONCLUSION: RYGB
      surgery is an effective treatment to reduce cardiovascular risk in Chinese
      diabetic patients with obesity.

PMID- 28744473
TI  - Corrigendum to "Are the Two Human Papillomavirus Vaccines Really Similar? A
      Systematic Review of Available Evidence: Efficacy of the Two Vaccines against
      HPV".
AB  - [This corrects the article DOI: 10.1155/2015/435141.].

PMID- 28744474
TI  - Erratum: Genetically expressed voltage sensor ArcLight for imaging large scale
      cortical activity in the anesthetized and awake mouse (erratum).
AB  - [This corrects the article DOI: 10.1117/1.NPh.4.3.031212.].

PMID- 28744476
TI  - Updates and Changes with JMI.
AB  - This JMI Editorial describes upcoming changes to the journal leadership for 2018.

PMID- 28744475
TI  - Mapping effective connectivity within cortical networks with diffuse optical
      tomography.
AB  - Understanding how cortical networks interact in response to task demands is
      important both for providing insight into the brain's processing architecture and
      for managing neurological diseases and mental disorders. High-density diffuse
      optical tomography (HD-DOT) is a neuroimaging technique that offers the
      significant advantages of having a naturalistic, acoustically controllable
      environment and being compatible with metal implants, neither of which is
      possible with functional magnetic resonance imaging. We used HD-DOT to study the
      effective connectivity and assess the modulatory effects of speech
      intelligibility and syntactic complexity on functional connections within the
      cortical speech network. To accomplish this, we extend the use of a generalized
      psychophysiological interaction (PPI) analysis framework. In particular, we apply
      PPI methods to event-related HD-DOT recordings of cortical oxyhemoglobin activity
      during auditory sentence processing. We evaluate multiple approaches for
      selecting cortical regions of interest and for modeling interactions among these
      regions. Our results show that using subject-based regions has minimal effect on
      group-level connectivity maps. We also demonstrate that incorporating an
      interaction model based on estimated neural activity results in significantly
      stronger effective connectivity. Taken together our findings support the use of
      HD-DOT with PPI methods for noninvasively studying task-related modulations of
      functional connectivity.

PMID- 28744477
TI  - Primal-dual approach to optical tomography with discretized path integral with
      efficient formulations.
AB  - We propose an efficient optical tomography with discretized path integral. We
      first introduce the primal-dual approach to solve the inverse problem formulated
      as a constraint optimization problem. Next, we develop efficient formulations for
      computing Jacobian and Hessian of the cost function of the constraint nonlinear
      optimization problem. Numerical experiments show that the proposed formulation is
      faster ([Formula: see text]) than the previous work with the log-barrier interior
      point method ([Formula: see text]) for the Shepp-Logan phantom with a grid size
      of [Formula: see text], while keeping the quality of the estimation results (root
      mean-square error increasing by up to 12%).

PMID- 28744478
TI  - Efficient orbital structures segmentation with prior anatomical knowledge.
AB  - We present a fully automatic method for segmenting orbital structures (globes,
      optic nerves, and extraocular muscles) in CT images. Prior anatomical knowledge,
      such as shape, intensity, and spatial relationships of organs and landmarks, were
      utilized to define a volume of interest (VOI) that contains the desired
      structures. Then, VOI was used for fast localization and successful segmentation
      of each structure using predefined rules. Testing our method with 30 publicly
      available datasets, the average Dice similarity coefficient for right and left
      sides of [0.81, 0.79] eye globes, [0.72, 0.79] optic nerves, and [0.73, 0.76]
      extraocular muscles were achieved. The proposed method is accurate, efficient,
      does not require training data, and its intuitive pipeline allows the user to
      modify or extend to other structures.

PMID- 28744479
TI  - Evolution of Cost-Free Resistance under Fluctuating Drug Selection in Pseudomonas
      aeruginosa.
AB  - Antibiotic resistance evolves rapidly in response to drug selection, but it can
      also persist at appreciable levels even after the removal of the antibiotic. This
      suggests that many resistant strains can both be resistant and have high fitness
      in the absence of antibiotics. To explore the conditions under which high
      fitness, resistant strains evolve and the genetic changes responsible, we used a
      combination of experimental evolution and whole-genome sequencing to track the
      acquisition of ciprofloxacin resistance in the opportunistic pathogen Pseudomonas
      aeruginosa under conditions of constant and fluctuating antibiotic delivery
      patterns. We found that high-fitness, resistant strains evolved readily under
      fluctuating but not constant antibiotic conditions and that their evolution was
      underlain by a trade-off between resistance and fitness. Whole-genome sequencing
      of evolved isolates revealed that resistance was gained through mutations in
      known resistance genes and that second-site mutations generally compensated for
      costs associated with resistance in the fluctuating treatment, leading to the
      evolution of cost-free resistance. Our results suggest that current therapies
      involving intermittent administration of antibiotics are contributing to the
      maintenance of antibiotic resistance at high levels in clinical settings.
      IMPORTANCE Antibiotic resistance is a global problem that greatly impacts human
      health. How resistance persists, even in the absence of antibiotic treatment, is
      thus a public health problem of utmost importance. In this study, we explored the
      antibiotic treatment conditions under which cost-free resistance arises, using
      experimental evolution of the bacterium Pseudomonas aeruginosa and the quinolone
      antibiotic ciprofloxacin. We found that intermittent antibiotic treatment led to
      the evolution of cost-free resistance and demonstrate that compensatory evolution
      is the mechanism responsible for cost-free resistance. Our results suggest that
      discontinuous administration of antibiotic may be contributing to the high levels
      of antibiotic resistance currently found worldwide.

PMID- 28744480
TI  - The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3
      Kinase on Early Chlamydia trachomatis Vacuoles.
AB  - Chlamydia trachomatis delivers multiple type 3 secreted effector proteins to host
      epithelial cells to manipulate cytoskeletal functions, membrane dynamics, and
      signaling pathways. TepP is the most abundant effector protein secreted early in
      infection, but its molecular function is poorly understood. In this report, we
      provide evidence that TepP is important for bacterial replication in cervical
      epithelial cells, activation of type I IFN genes, and recruitment of class I
      phosphoinositide 3-kinases (PI3K) and signaling adaptor protein CrkL to nascent
      pathogen-containing vacuoles (inclusions). We also show that TepP is a target of
      tyrosine phosphorylation by Src kinases but that these modifications do not
      appear to influence the recruitment of PI3K or CrkL. The translocation of TepP
      correlated with an increase in the intracellular pools of phosphoinositide
      (3,4,5)-triphosphate but not the activation of the prosurvival kinase Akt,
      suggesting that TepP-mediated activation of PI3K is spatially restricted to early
      inclusions. Furthermore, we linked PI3K activity to the dampening of
      transcription of type I interferon (IFN)-induced genes early in infection.
      Overall, these findings indicate that TepP can modulate cell signaling and,
      potentially, membrane trafficking events by spatially restricted activation of
      PI3K. IMPORTANCE This article shows that Chlamydia recruits PI3K, an enzyme
      important for host cell survival and internal membrane functions, to the
      pathogens inside cells by secreting a scaffolding protein called TepP. TepP
      enhances Chlamydia replication and dampens the activation of immune responses.

PMID- 28744481
TI  - Visualizing Antimicrobials in Bacterial Biofilms: Three-Dimensional Biochemical
      Imaging Using TOF-SIMS.
AB  - Bacterial biofilms are groups of bacteria that exist within a self-produced
      extracellular matrix, adhering to each other and usually to a surface. They grow
      on medical equipment and inserts such as catheters and are responsible for many
      persistent infections throughout the body, as they can have high resistance to
      many antimicrobials. Pseudomonas aeruginosa is an opportunistic pathogen that can
      cause both acute and chronic infections and is used as a model for research into
      biofilms. Direct biochemical methods of imaging of molecules in bacterial
      biofilms are of high value in gaining a better understanding of the fundamental
      biology of biofilms and biochemical gradients within them. Time of flight
      secondary-ion mass spectrometry (TOF-SIMS) is one approach, which combines
      relatively high spatial resolution and sensitivity and can perform depth
      profiling analysis. It has been used to analyze bacterial biofilms but has not
      yet been used to study the distribution of antimicrobials (including antibiotics
      and the antimicrobial metal gallium) within biofilms. Here we compared two
      methods of imaging of the interior structure of P. aeruginosa in biological
      samples using TOF-SIMS, looking at both antimicrobials and endogenous
      biochemicals: cryosectioning of tissue samples and depth profiling to give pseudo
      three-dimensional (pseudo-3D) images. The sample types included both simple
      biofilms grown on glass slides and bacteria growing in tissues in an ex vivo pig
      lung model. The two techniques for the 3D imaging of biofilms are potentially
      valuable complementary tools for analyzing bacterial infection. IMPORTANCE Modern
      analytical techniques are becoming increasingly important in the life sciences;
      imaging mass spectrometry offers the opportunity to gain unprecedented amounts of
      information on the distribution of chemicals in samples-both xenobiotics and
      endogenous compounds. In particular, simultaneous imaging of antibiotics (and
      other antimicrobial compounds) and bacterium-derived metabolites in complex
      biological samples could be very important in the future for helping to
      understand how sample matrices impact the survival of bacteria under antibiotic
      challenge. We have shown that an imaging mass spectrometric technique, TOF-SIMS,
      will be potentially extremely valuable for this kind of research in the future.

PMID- 28744482
TI  - Induction of beta-Lactamase Activity and Decreased beta-Lactam Susceptibility by
      CO2 in Clinical Bacterial Isolates.
AB  - Antimicrobial susceptibility testing of clinical isolates is a crucial step
      toward appropriate treatment of infectious diseases. The clinical isolate
      Francisella philomiragia 14IUHPL001, recently isolated from a 63-year-old woman
      with atypical pneumonia, featured decreased susceptibility to beta-lactam
      antibiotics when cultivated in 5% CO2. Quantitative beta-lactamase assays
      demonstrated a significant (P < 0.0001) increase in enzymatic activity between
      bacteria cultivated in 5% CO2 over those incubated in ambient air. The presence
      of beta-lactamase genes blaTEM and blaSHV was detected in the clinical isolate F.
      philomiragia 14IUHPL001 by PCR, and the genes were positively identified by
      nucleotide sequencing. Expression of blaTEM and blaSHV was detected by reverse
      transcription-PCR during growth at 5% CO2 but not during growth in ambient air. A
      statistically significant alkaline shift was observed following cultivation of F.
      philomiragia 14IUHPL001 in both ambient air and 5% CO2, allowing desegregation of
      the previously reported effects of acidic pH from the currently reported effect
      of 5% CO2 on blaTEM and blaSHV beta-lactamases. To ensure that the observed
      phenomenon was not unique to F. philomiragia, we evaluated a clinical isolate of
      blaTEM-carrying Haemophilus influenzae and found parallel induction of blaTEM
      gene expression and beta-lactamase activity at 5% CO2 relative to ambient air.
      IMPORTANCE beta-Lactamase induction and concurrent beta-lactam resistance in
      respiratory tract pathogens as a consequence of growth in a physiologically
      relevant level of CO2 are of clinical significance, particularly given the
      ubiquity of TEM and SHV beta-lactamase genes in diverse bacterial pathogens. This
      is the first report of beta-lactamase induction by 5% CO2.

PMID- 28744483
TI  - Erratum for Linz et al., "Bacterial Community Composition and Dynamics Spanning
      Five Years in Freshwater Bog Lakes".
AB  - [This corrects the article DOI: 10.1128/mSphere.00169-17.].

PMID- 28744484
TI  - The Protein Interactome of Streptococcus pneumoniae and Bacterial Meta
      interactomes Improve Function Predictions.
AB  - The functions of roughly a third of all proteins in Streptococcus pneumoniae, a
      significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid
      approach, we have determined more than 2,000 novel protein interactions in this
      organism. We augmented this network with meta-interactome data that we defined as
      the pool of all interactions between evolutionarily conserved proteins in other
      bacteria. We found that such interactions significantly improved our ability to
      predict a protein's function, allowing us to provide functional predictions for
      299 S. pneumoniae proteins with previously unknown functions. IMPORTANCE
      Identification of protein interactions in bacterial species can help define the
      individual roles that proteins play in cellular pathways and pathogenesis. Very
      few protein interactions have been identified for the important human pathogen S.
      pneumoniae. We used an experimental approach to identify over 2,000 new protein
      interactions for S. pneumoniae, the most extensive interactome data for this
      bacterium to date. To predict protein function, we used our interactome data
      augmented with interactions from other closely related bacteria. The combination
      of the experimental data and meta-interactome data significantly improved the
      prediction results, allowing us to assign possible functions to a large number of
      poorly characterized proteins.

PMID- 28744485
TI  - Combining Genome-Scale Experimental and Computational Methods To Identify
      Essential Genes in Rhodobacter sphaeroides.
AB  - Rhodobacter sphaeroides is one of the best-studied alphaproteobacteria from
      biochemical, genetic, and genomic perspectives. To gain a better systems-level
      understanding of this organism, we generated a large transposon mutant library
      and used transposon sequencing (Tn-seq) to identify genes that are essential
      under several growth conditions. Using newly developed Tn-seq analysis software
      (TSAS), we identified 493 genes as essential for aerobic growth on a rich medium.
      We then used the mutant library to identify conditionally essential genes under
      two laboratory growth conditions, identifying 85 additional genes required for
      aerobic growth in a minimal medium and 31 additional genes required for
      photosynthetic growth. In all instances, our analyses confirmed essentiality for
      many known genes and identified genes not previously considered to be essential.
      We used the resulting Tn-seq data to refine and improve a genome-scale metabolic
      network model (GEM) for R. sphaeroides. Together, we demonstrate how genetic,
      genomic, and computational approaches can be combined to obtain a systems-level
      understanding of the genetic framework underlying metabolic diversity in
      bacterial species. IMPORTANCE Knowledge about the role of genes under a
      particular growth condition is required for a holistic understanding of a
      bacterial cell and has implications for health, agriculture, and biotechnology.
      We developed the Tn-seq analysis software (TSAS) package to provide a flexible
      and statistically rigorous workflow for the high-throughput analysis of insertion
      mutant libraries, advanced the knowledge of gene essentiality in R. sphaeroides,
      and illustrated how Tn-seq data can be used to more accurately identify genes
      that play important roles in metabolism and other processes that are essential
      for cellular survival.

PMID- 28744486
TI  - Multi-omics Analysis of Periodontal Pocket Microbial Communities Pre- and
      Posttreatment.
AB  - Periodontitis is a polymicrobial infectious disease that causes breakdown of the
      periodontal ligament and alveolar bone. We employed a meta-omics approach that
      included microbial 16S rRNA amplicon sequencing, shotgun metagenomics, and tandem
      mass spectrometry to analyze sub- and supragingival biofilms in adults with
      chronic periodontitis pre- and posttreatment with 0.25% sodium hypochlorite.
      Microbial samples were collected with periodontal curettes from 3- to 12-mm-deep
      periodontal pockets at the baseline and at 2 weeks and 3 months. All data types
      showed high interpersonal variability, and there was a significant correlation
      between phylogenetic diversity and pocket depth at the baseline and a strong
      correlation (rho = 0.21; P = 0.008) between metabolite diversity and maximum
      pocket depth (MPD). Analysis of subgingival baseline samples (16S rRNA and
      shotgun metagenomics) found positive correlations between abundances of
      particular bacterial genera and MPD, including Porphyromonas, Treponema,
      Tannerella, and Desulfovibrio species and unknown taxon SHD-231. At 2 weeks
      posttreatment, we observed an almost complete turnover in the bacterial genera
      (16S rRNA) and species (shotgun metagenomics) correlated with MPD. Among the
      metabolites detected, the medians of the 20 most abundant metabolites were
      significantly correlated with MPD pre- and posttreatment. Finally, tests of
      periodontal biofilm community instability found markedly higher taxonomic
      instability in patients who did not improve posttreatment than in patients who
      did improve (UniFrac distances; t = -3.59; P = 0.002). Interestingly, the
      opposite pattern occurred in the metabolic profiles (Bray-Curtis; t = 2.42; P =
      0.02). Our results suggested that multi-omics approaches, and metabolomics
      analysis in particular, could enhance treatment prediction and reveal patients
      most likely to improve posttreatment. IMPORTANCE Periodontal disease affects the
      majority of adults worldwide and has been linked to numerous systemic diseases.
      Despite decades of research, the reasons for the substantial differences among
      periodontitis patients in disease incidence, progressivity, and response to
      treatment remain poorly understood. While deep sequencing of oral bacterial
      communities has greatly expanded our comprehension of the microbial diversity of
      periodontal disease and identified associations with healthy and disease states,
      predicting treatment outcomes remains elusive. Our results suggest that combining
      multiple omics approaches enhances the ability to differentiate among disease
      states and determine differential effects of treatment, particularly with the
      addition of metabolomic information. Furthermore, multi-omics analysis of biofilm
      community instability indicated that these approaches provide new tools for
      investigating the ecological dynamics underlying the progressive periodontal
      disease process.

PMID- 28744487
TI  - Gefitinib versus Docetaxel in Treated Non-small-cell Lung Cancer: A Meta
      analysis.
AB  - : The objective of this study was to perform a meta-analysis to evaluate the
      efficacy and toxicity of gefitinib and docetaxel in treated patients with non
      small-cell lung cancer (NSCLC). METHODS: A literature search was performed using
      PubMed and CNKI databases for relevant keywords and the Medical Subject Headings.
      After further full-text screening, 10 clinical trials were included in the final
      meta-analysis. Specific odds ratios (OR) and confidence intervals were
      calculated. RESULTS: The outcomes of treatment efficacy included disease control
      rates, quality-of-life improvement rates, 3~4 grade adverse events. Comparing
      gefitinib to docetaxel for NSCLC patients, the pooled odds ratios (OR) of disease
      control rates was 1.09, (95% confidential index [CI] = 0.84-1.43), the pooled OR
      of quality-of-life improvement rates was 2.49, (95% CI = 1.77-3.49), the pooled
      OR of 3~4 grade adverse events was 0.49, (95% CI = 0.32-0.75). CONCLUSION:
      Gefitinib was found to significantly improve patients' quality-of-life and
      obviously decrease patients' adverse events of 3~4 grade.There is no difference
      of disease control rates between gefitinib and docetaxel.

PMID- 28744488
TI  - Pathophysiology of Meningioma Growth in Pregnancy.
AB  - Meningioma is among the most frequent brain tumours predominantly affecting
      elderly women. Epidemiological studies have shown that at the age of fertility
      the incidence is relatively low. The biological behaviour of meningioma in
      pregnancy is different from other meningiomas. The possible explanation is rooted
      in the complex physiological changes and hormonal differences during pregnancy.
      The increased meningioma growth observed in pregnancy is presumably the result of
      endocrine mechanisms. These include increase in progesterone, human placental
      lactogen (hPL) and prolactin (PRL) serum levels. In contrast, levels of pituitary
      hormones such as follicle stimulating hormone (FSH), luteinizing hormone (LH) and
      human chorionic gonadotropin (hCG) produced by the placenta are decreasing in the
      mother prior to childbirth. Besides, vascular factors also play a crucial role.
      Peritumoral brain edema (PTBE), with well-known causative association with
      vascular endothelial growth factor (VEGF), can often be seen both with imaging
      and in the surgical specimens. Our aim is to assess published research on this
      topic including diagnostic and therapeutic guidelines, and to provide a
      clinically useful overview on the pathophysiology and biological behaviour of
      this rare complication of pregnancy.

PMID- 28744489
TI  - Galectin-3 Expression in Colorectal Cancer and its Correlation with Clinical
      Pathological Characteristics and Prognosis.
AB  - OBJECTIVE: To explore the expression levels of galectin-3 in colorectal cancer
      and the association between galectin-3 and its clinical pathological parameters,
      as well as the prognosis of colorectal cancer patients. METHODS: An
      immunohistochemistry assay was used to test the expression levels of galectin-3
      in cancer tissues of 61 colorectal cancer cases and in normal intestinal tissues
      adjacent to the cancer tissues of 23 cases. The associations between protein
      expression levels of galectin-3 and the clinicopathological features, such as
      age, sex, pathology type, lymphatic metastasis, and prognosis were also analyzed.
      RESULTS: The positive rate of galectin-3 in cancer tissues was significantly
      higher than that of cancer-adjacent tissues: 62.5% (38/61) versus 13.0% (3/23)
      (P<0.05), respectively. Correlation was found between the protein expression of
      galectin-3 and the tumor size (P<0.05), as well as between the tumor
      differentiation (P<0.05) and Duke staging (P<0.05). The median progression-free
      survival times of patients with galectin-3 positive and negative expression were
      19.2 and 35.1 months, respectively, with significant statistical difference
      (P<0.05). CONCLUSION: Galectin-3 expression was correlated with the genesis and
      development of colorectal cancer and which could be used a biological marker for
      the prognosis of colorectal cancer patients.

PMID- 28744490
TI  - June 2017, JSS.

PMID- 28744491
TI  - Interlaminar endoscopic lateral recess decompression-surgical technique and early
      clinical results.
AB  - BACKGROUND: Lateral recess stenosis is a common pathology causing de-novo or
      residual radicular pain following lumbar spine surgery. Diagnostic criteria and
      treatment strategies for symptomatic lateral recess stenosis are not well
      established. METHODS: We identified ten patients in our prospective patient
      database (n=146) who underwent endoscopic interlaminar decompression for
      unilateral symptomatic lateral recess stenosis. Lateral recess height and angle
      were measured on axial T2-weighted MRI. Values from the symptomatic side were
      compared to the contralateral side which served as asymptomatic control. Oswestry
      Disability Index (ODI) and Visual Analogue Scale (VAS) for back and leg pain were
      collected preoperatively, postoperatively and at last follow-up. RESULTS:
      Preoperative MRI revealed that both lateral recess angle and height were
      significantly smaller on the symptomatic compared to the asymptomatic side
      (angle: 19.3 degrees  vs. 35.7 degrees ; height: 2.9 vs. 5.7 mm; P<0.01). All
      patients tolerated endoscopic interlaminar decompression well and half of the
      patients were discharged on the day of surgery. At last follow-up (12.6+/-1.7
      months), 8 out of 10 patients experienced a minimally clinically important
      improvement of their VAS for ipsilateral leg pain, which improved from 7.2+/-0.5
      preoperatively to 2.5+/-0.8 postoperatively (P=0.001). The back pain VAS also
      improved (preoperatively 5.1+/-1.1 vs. postoperatively 1.7+/-0.9, P<0.05). The
      ODI improved from 50+/-5.8 preoperatively to 22.2+/-5.1 at last follow-up
      (P=0.001). One patient experienced persistent leg pain. CONCLUSIONS: Lateral
      recess height and angle correlate with symptomatic lateral recess stenosis which
      is effectively treated utilizing interlaminar endoscopic lateral recess
      decompression.

PMID- 28744492
TI  - Relationship between depression and clinical outcome following anterior cervical
      discectomy and fusion.
AB  - BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is a commonly
      performed procedure for patients with symptomatic degenerative conditions of the
      cervical spine. The objective is to assess the impact of preoperative depression
      and other baseline characteristics on patient reported clinical outcomes
      following ACDF surgery based on the experience at our institution. METHODS: This
      was a retrospective cohort study of some patients undergoing ACDF at a single
      institution from 2012 to 2014. Ninety-three patients that underwent an ACDF
      procedure were included. The primary outcome measure was post-operative Nurick
      score. RESULTS: Sixteen (17.2%) patients had a formal diagnosis of depression
      compared to 77 (82.8%) patients without depression. On univariate analysis,
      patients with depression had statistically significantly higher Nurick scores
      compared to patients without depression after surgery (coefficient =0.55, 95% CI:
      0.21-0.90, P=0.002). On multivariate analysis, there was a trend toward higher
      postoperative Nurick scores in patients that had depression (coefficient =0.31,
      95% CI: -0.01-0.63, P=0.057). CONCLUSIONS: This small retrospective study reveals
      an inverse relationship between preoperative depression and functional outcome.
      Further research should be performed to investigate this relationship and to
      investigate if treating depression can improve postoperative outcomes.

PMID- 28744493
TI  - Lumbar fusion surgery for degenerative conditions is associated with significant
      resource and narcotic use 2 years postoperatively in the commercially insured: a
      medical and pharmacy claims study.
AB  - BACKGROUND: Chronic back pain is one of the costliest and most complex medical
      conditions to manage, involving physiological, psychological, mechanical, social,
      and environmental factors. An increasing trend of lumbar fusion (LF) surgery for
      chronic back pain continues despite conflicting evidence for pain relief or
      improved long-term outcomes. Our goal was to assess medical and pharmacy
      utilization (including continued use of pain medication) over a 2-year period
      among patients receiving LF to relieve back pain for degenerative conditions
      without instability. METHODS: We conducted a 2-year longitudinal cohort study of
      1,422 commercially insured patients who received LF from January through
      September 2009, and who had continuous benefit eligibility through 2011. We
      assessed resource use among patients with ICD-9-CM diagnostic codes consistent
      with a degenerative condition, identified from Cigna's national claim database
      (CPT codes 22612, 22630 and/or 22558). Patients with fracture, tumor, infection,
      spondylolisthesis, inflammatory arthritis, or deformity diagnostic codes were
      excluded. RESULTS: Over the 2 years following LF, 992 patients (70%) incurred
      $9.0 million in additional medical claims payments which averaged $9,383 per
      patient. These payments included pain management interventions and long term
      therapy services in 30% of patients. A subset of 850 patients (60%) also had
      pharmacy benefits and 829 (97.5%) received multiple pain-related classes of
      medication over the same period. The majority of patients continued on chronic
      narcotic use (62.5%), and 95% of patients on narcotics preoperatively continued
      narcotic utilization at two years. This pharmacy benefit subset incurred an
      additional $2.2 million for pain-related medications at an average cost of $2,600
      per patient. Total average payment for patients with combined medical and
      pharmacy benefits was $12,283. CONCLUSIONS: LF for patients with a degenerative
      lumbar diagnosis incurred significant resources postoperatively, and was followed
      by long-term pain and psychotropic medication utilization.

PMID- 28744494
TI  - Assessing the effectiveness of routine use of post-operative in-patient physical
      therapy services.
AB  - BACKGROUND: The association between functional decline occurring with prolonged
      bed rest after surgery is well-known. Immediate in-patient post-operative
      ambulation with the physical therapy (PT) service has been reported to improve
      pain and disability, while decreasing the incidence of perioperative
      complications. Whether formal PT evaluation prior to hospital discharge leads to
      improved ambulation (number of steps ambulated), shorter duration of hospital
      stay and lower peri-operative complications compared to nurse-assisted ambulation
      protocols remain unknown. METHODS: The medical records of 274 patients (No PT:
      n=87, PT: n=187) undergoing elective spine surgery at a major academic medical
      center were reviewed. Patients were categorized based on whether PT services were
      delivered during the post-operative in-patient stay. Patient demographics,
      comorbidities, and post-operative complication rates were collected and compared.
      Ambulation status and the number of steps ambulated were recorded. RESULTS:
      Baseline characteristics were similar in both cohorts. Operative variables were
      similar between both cohorts, with no significant difference in operative time,
      estimated blood loss (EBL), and number of fusion levels. Peri-operative
      complication rates were similar between the cohorts. Compared to patients in the
      nurse-assisted ambulation cohort (No PT), patients in the PT cohort had a longer
      duration of hospital stay (4.17 vs. 3.39 days, P=0.15). 30-day readmission rates,
      although higher in the PT cohort, was not statistically significantly different
      (PT 6.57% vs. No PT: 2.30%, P=0.13). CONCLUSIONS: Our study suggests that the
      routine use of the PT services compared to nurse-assisted ambulation programs is
      associated with a modest increase in the duration of hospital stay without any
      significant reduction in peri-operative complications profile. In a health
      conscious healthcare climate, appropriate screening mechanisms and risk
      stratification should be performed to optimize utilization of post-operative in
      patient PT services.

PMID- 28744495
TI  - Effects of immediate post-operative pain medication on length of hospital stay:
      does it make a difference?
AB  - BACKGROUND: Patient reported outcomes and length of hospital stay (LOS) are being
      used as a proxy for hospital care. An extra day of hospitalization costs
      thousands of health care dollars. The choice of intraoperative pain medications
      has been associated with decreased pain scores in other surgical subspecialties.
      However, the effects of immediate post-operative patient-controlled analgesics
      (PCA)/intravenous (IV) pain medication on patient care are not well understood in
      spine surgery. The aim of this study is to determine the effects of different
      immediate post-operative pain medications on post-operative complications
      profile, LOS, and patient reported outcomes (PROs) after elective spine surgery.
      METHODS: The medical records of 230 patients (morphine: n=98, fentanyl: n=61,
      hydromorphone: n=71) undergoing elective spine surgery at a major academic
      medical center were reviewed. Patients were categorized by the immediate post
      operative pain medication they were on, with the most common medications being
      PCA/IV morphine, fentanyl, and hydromorphone. Patient demographics,
      comorbidities, and post-operative complication rates were collected. All patients
      had retrospectively collected outcomes measures and a minimum of 6-month follow
      up. Patient reported outcomes instruments [Oswestry Disability Index (ODI), SF-36
      and Neck/Back/Leg-Pain Visual Analog Scale (VAS-NP/BP/LP)] were completed before
      surgery, then at 3- and 6-month after surgery. RESULTS: Baseline characteristics
      were similar in all cohorts. Operative variables were also similar in all
      cohorts, with no difference in operative time, estimated blood loss (EBL), or
      fusion levels. Complication rates were similar between cohorts, with the fentanyl
      cohort having an increased percentage of urinary tract infection (UTI) than the
      morphine and hydromorphone cohorts (16.39% vs. 5.15% vs. 5.63%, P=0.0277). The
      morphine-cohort had a decreased LOS than the fentanyl and hydromorphone cohorts
      (4.18 vs. 5.56 vs. 5.69 days, P=0.0376). There was a significant difference in
      the number of feet first ambulated by the patient post-operatively for the
      morphine and hydromorphone cohorts than the fentanyl-cohort (morphine: 118.44+/
      18.15 vs. fentanyl: 59.26+/-20.78 vs. hydromorphone: 125.91+/-19.85, P=0.0420).
      There was no significant differences in 30-day hospital readmission rates between
      the cohorts, morphine-cohort did trend lower than the other cohorts (morphine:
      5.10 vs. fentanyl: 11.48 vs. hydromorphone: 11.27, P=0.2492). There were no
      significant differences in PROs between the two cohorts in ODI, SF-36, and VAS
      NP/BP/LP at baseline, 3- and 6-month. CONCLUSIONS: Our study demonstrates that
      the choice of immediate post-operative pain medication can make a difference in
      the hospital course for patients. Identifying these types of factors might help
      increase patient care and reduce health care costs.

PMID- 28744496
TI  - Elastic modulus in the selection of interbody implants.
AB  - BACKGROUND: The modulus of elasticity of an assortment of materials used in
      spinal surgery, as well as cortical and cancellous bones, is determined by direct
      measurements and plotting of the appropriate curves. When utilized in spine
      surgery, the stiffness of a surgical implant can affect its material
      characteristics. The modulus of elasticity, or Young's modulus, measures the
      stiffness of a material by calculating the slope of the material's stress-strain
      curve. While many papers and presentations refer to the modulus of elasticity as
      a reason for the choice of a particular spinal implant, no peer-reviewed surgical
      journal article has previously been published where the Young's modulus values of
      interbody implants have been measured. METHODS: Materials were tested under pure
      compression at the rate of 2 mm/min. A maximum of 45 kilonewtons (kN) compressive
      force was applied. Stress-strain characteristics under compressive force were
      plotted and this plot was used to calculate the elastic modulus. RESULTS: The
      elastic modulus calculated for metals was more than 50 Gigapascals (GPa) and had
      significantly higher modulus values compared to poly-ether-ether-ketone (PEEK)
      materials and allograft bone. CONCLUSIONS: The data generated in this paper may
      facilitate surgeons to make informed decisions on their choices of interbody
      implants with specific attention to the stiffness of the implant chosen.

PMID- 28744497
TI  - Subsidence following anterior lumbar interbody fusion (ALIF): a prospective
      study.
AB  - BACKGROUND: Anterior lumbar interbody fusion (ALIF) is a widely used surgical
      technique for disorders of the lumbar spine. One potential complication is the
      subsidence of disc height in the post-operative period. Few studies have reported
      the rate of subsidence in ALIF surgery prospectively. We prospectively evaluated
      the rate of subsidence in adult patients undergoing ALIF. METHODS: Results were
      obtained by reviewing scans of 147 patients. Disc heights were measured on
      radiographic scans taken pre-operatively in addition to post-operatively
      immediately, at 6 weeks and at 18 months. The anterior and posterior
      intervertebral disc heights were measured. Subsidence was defined as greater than
      or equal to 2 mm loss of height. RESULTS: A total of 15 patients (10.2%) had
      subsidence, with 7 being male. Each case was of delayed cage subsidence (DCS) >6
      weeks postoperatively. The mean subsidence was 4.7 mm (range, 2.4-7.8). Mean
      anterior disc height was 8.6+/-0.4 mm preoperatively, which improved to 15.1+/
      0.5 mm at latest follow-up. Mean posterior disc height was 4.7+/-0.2 mm
      preoperatively, which improved to 8.7+/-0.4 mm at latest follow-up. The mean
      lumbar lordosis (LL) angle was 42.5 degrees +/-10.8 degrees  and the mean local
      disc angle (LDA) was 6.7 degrees +/-4.0 degrees . The 91.2% (n=114/125) of
      patients with appropriate radiological follow-up demonstrated fusion by latest
      follow-up. There was no correlation between subsidence rate with patient reported
      outcomes [Visual Analog Scale (VAS), Oswestry Disability Index (ODI) and Short
      Form 12 Item survey (SF-12)] and fusion rates. There was a significant negative
      correlation between LL and extent of subsidence (Pearson correlation =-0.754,
      P=0.012). CONCLUSIONS: In conclusion, we found that the subsidence rate at follow
      up was generally low following standalone ALIF for this patient series. Patient
      clinical outcomes and bony fusion rates were not significantly influenced by
      subsidence.

PMID- 28744498
TI  - Ex vivo 1H MR spectroscopy and histology after experimental chronic spinal cord
      compression.
AB  - BACKGROUND: Proton magnetic resonance imaging (MRS) is used increasingly to image
      the spinal cord in compressive cervical myelopathy (CSM). However, detailed
      analyses of the underlying histomorphological changes leading to MRS alterations
      are still lacking. The aim of our study was to correlate neuroimaging and
      neuropathologic alterations in a rabbit myelopathy model. METHODS: Chronic spinal
      cord compression was induced in a rabbit model (n=16) allowing for a gradual 270
      degrees  compression of the spinal cord. Spinal cord compression core areas were
      divided into two samples for (A) 1H MRS and (B) histopathological analyses.
      Postoperatively the animals underwent a neurological examination twice a day and
      outcome was categorized in pattern of injury and amount of recovery. RESULTS:
      Three groups were observed and categorized: (I) animals with severe deficits and
      no or minimal recovery; (II) animals with severe deficits and complete or almost
      complete recovery; (III) animals with mild to moderate deficits and a complete
      recovery. Significant differences in the lesioned spinal cords between the
      different recovery groups were found for N-acetyl-aspartate and choline. NAA/Cr
      was detected significantly (P<0.001, ANOVA) less in the group that did show
      permanent neurological deficits. To the contrary, choline was detected
      significantly (P<0.001, ANOVA) more in the group that did show permanent
      neurological deficits. Histologically the first group showed more apoptosis and
      necrosis than the second and third group. CONCLUSIONS: MR spectroscopy (MRS) may
      be helpful for clinicians in improving the prognostic accuracy in cervical
      myelopathies since this method nicely reflects the extent and severity of spinal
      cord damage.

PMID- 28744499
TI  - The contribution of the cortical shell to pedicle screw fixation.
AB  - BACKGROUND: A pedicle screw insertion technique known as "hubbing" involves the
      removal of cortical bone around the screw insertion with the aim of improving
      fixation and decreasing screw loosening. However, the efficacy of this procedure
      relative to bone density and early loading have not been fully explored. The
      purpose of this study is to establish the contribution of the cortical layer
      (hubbing), cancellous density, early loading (toggling) in an idealised model.
      This is an in vitro laboratory study. METHODS: Synthetic bone blocks with
      cancellous bulk and a simulated cortical shell were implanted with 6.5 mm pedicle
      screws. Three key variables were evaluated in this study; density of the
      simulated bone (10-20 lb/ft3), toggling (+/-0.5 mm for 10,000 cycles), and the
      presence or absence of the surrounding cortex (hubbing). Pullout testing after
      toggling was performed to determine maximum load, stiffness and energy. Results
      were analyzed to assess interaction and main effects. RESULTS: Removal of the
      cortex decreased the pullout loads by approximately 1,100 N after toggling.
      Toggling in the presence of the cortical shell had no effect. However, once the
      cortical shell is removed damage to the weaker cancellous bone accumulates and
      further compromises the fixation. CONCLUSIONS: The addition of a cortical layer
      in the Sawbone model is significant and provides a more realistic model of load
      sharing. The cortex plays a considerable role in the protection of underlying
      cancellous bone as well as contributing to initial pullout strength. The results
      of this study demonstrate a negative synergistic effect when both toggling and
      hubbing are applied to the weaker bone.

PMID- 28744500
TI  - Accuracy of minimally invasive percutaneous thoracolumbar pedicle screws using 2D
      fluoroscopy: a retrospective review through 3D CT analysis.
AB  - BACKGROUND: In the literature, there is a large variation in the reported
      misplacement rates of pedicle screws. The use of minimally invasive surgical
      techniques is increasing and as such there has only been a small amount of data
      to look at the misplacement rate of percutaneously inserted thoracic and lumbar
      pedicle screws. METHODS: A retrospective analysis of post-operative computed
      tomography (CT) scans were performed on 108 patients who underwent minimally
      invasive percutaneously inserted thoracic and lumbar pedicle screws by a single
      surgeon. Analysis of the screw trajectory using strict guidelines was performed
      using multiplanar reconstruction CT scan data to determine the accuracy of the
      pedicle screws. RESULTS: A total of 614 screws were inserted in vertebral levels
      T2 to S1. Twenty-five (4.07%) screws were considered misplaced having breached
      the pedicular cortex. Thoracic pedicle screws had a statistically higher
      misplacement rate than lumbar pedicle screws (14.67% vs. 2.60% respectively,
      P<0.001). A single screw required replacement (0.16%) and there were no permanent
      neurological deficits. The misplacement rates were lower than those reported for
      open screw placement and equivalent to 3D CT navigated misplacement rates.
      CONCLUSIONS: Percutaneously inserted pedicle screws using 2D fluoroscopy offers a
      safe and accurate option for spinal stabilisation with an extremely low
      misplacement rate and morbidity. Overall, the low misplacement rates were
      equivalent and in most cases lower compared to open and computer assisted
      navigation techniques. However, we would recommend that given a misplacement rate
      of 14.67% for thoracic pedicle screws that computer assisted navigation may be
      able to offer further improvements in accuracy.

PMID- 28744501
TI  - Proximal junctional kyphosis in adult spinal deformity with long spinal fusion
      from T9/T10 to the ilium.
AB  - BACKGROUND: Proximal junctional kyphosis (PJK) is a common complication after
      corrective long spinal fusion for adult spinal deformity. Although some reports
      evaluated PJK after corrective long spinal fusion, there is no report about
      analysis of PJK cases in the same fusion area. The purpose of this study to
      investigated the incidence of and risk factors for PJK in adults undergoing long
      spinal fusion from the distal thoracic vertebrae (T9/T10) to the ilium. METHODS:
      We enrolled 56 adult patients (>40 years of age) who underwent posterior
      corrective surgery with same fusion area from T9 or T10 to the ilium for spinal
      deformity. Pre- and postoperative radiographic measurements included the sagittal
      vertical axis (SVA), lumbar lordosis (LL), thoracic kyphosis (TK), pelvic tilt
      (PT), and pelvic incidence minus LL (PI-LL). The Oswestry disability index (ODI)
      was used to evaluate patient outcomes preoperatively and one year after surgery.
      We analyzed the incidence for PJK and compared PJK and non-PJK cases. RESULTS:
      PJK at the final follow-up occurred in 19 of 56 (33.9%) patients. The mean age
      and ODI were not significantly different between the PJK and non-PJK groups. Both
      two groups had good spinopelvic sagittal alignment after surgery in terms of SVA
      and PI-LL. Only three cases required revision surgery for symptomatic PJK. Three
      cases had history of rheumatoid arthritis and/or total hip arthroplasty surgery.
      CONCLUSIONS: The incidence of PJK was 33.9%, and ODI was not significantly
      different between the PJK and non-PJK groups. Symptomatic PJK was only three
      cases and all of them had lower extremity joint disorders. We should pay
      attention also lower extremity joint to prevent symptomatic PJK at the lower
      thoracic level.

PMID- 28744502
TI  - Static and dynamic cervical MRI: two useful exams in cervical myelopathy.
AB  - BACKGROUND: Cervical magnetic resonance imaging (MRI) is the gold standard exam
      in the assessment of patients affected by cervical myelopathy and is very useful
      in planning the operation. Herein we present a series of patients affected by
      long tract symptoms who underwent dynamic MRI in addition to the static exam.
      METHODS: In the period between March 2010 and March 2012, three-hundred-ten
      patients referred to our department since affected by neck/arm pain or symptoms
      related to cervical myelopathy. Thirty-eight patients complained "long-tract
      symptoms" related to cervical myelopathy. This series of patients was enrolled in
      the study. All patients underwent clinical and neurological exam. In all the
      cases, a static and dynamic cervical MRI was executed using a 3.0-T
      superconducting MR unit (Intera, Philips, Eindhoven, Netherlands). The dynamic
      exam was performed with as much neck flexion and extension the patient could
      achieve alone. On T2-weigthed MRI each level was assessed independently by two
      neuroradiologists and Muhle scale was applied. RESULTS: According to Muhle's
      classification of spinal cord compressions, static MRI demonstrated 156 findings:
      96 (61.54%) anterior and 60 (38.46%) posterior. Dynamic MRI showed 186 spinal
      cord compressions: 81 (43.5%) anterior and 105 (56.5%) posterior. The anterior
      compressions were: grade 1 in 23 cases (28.4%), grade 2 in 52 cases (64.2%),
      grade 3 in 6 cases (7.4%). The posterior compressions were: 32 (30.48%) of grade
      1, 60 (57.14%) of grade 2, 13 (12.38%) of grade 3. CONCLUSIONS: The dynamic MRI
      demonstrated a major number of findings and spinal cord compressions compared to
      the static exam. Finally, we consider the dynamic exam able to provide useful
      information in these patients, but we suggest a careful evaluation of the
      findings in the extension exam since they are probably over-expressed.

PMID- 28744503
TI  - Blunt vertebral vascular injury in trauma patients: ATLS(r) recommendations and
      review of current evidence.
AB  - Blunt cerebrovascular injury (BCVI) encompasses two distinct clinical entities:
      traumatic carotid artery injury (TCAI) and traumatic vertebral artery injury
      (TVAI). The latter is the focus of our review. These are potentially devastating
      injuries which pose a diagnostic challenge in the acute trauma setting. There is
      still debate regarding the optimal screening criteria, diagnostic imaging
      modality and treatment methods. In 2012 the American College of Surgeons proposed
      criteria for investigating patients with suspected TVAI and subsequent treatment
      methods, caveated with the statement that evidence is limited and still evolving.
      Here we review the historical evidence and recent literature relating to these
      recommendations.

PMID- 28744504
TI  - Anterior lumbar vertebrectomy via direct anterior approach: technical note.

PMID- 28744505
TI  - Intraoperative navigation for accurate midline placement of anterior lumbar
      interbody fusion and total disc replacement prosthesis.
AB  - Anterior lumbar approach techniques for the management of discogenic back pain
      and placement of spinal instrumentation such as fusion and disc replacement
      prosthesis is becoming increasingly popular. To date, no studies have reported
      the clinical usage of spinal navigation with anterior lumber interbody fusion
      (ALIF) and total disk replacement (TDR). We describe a surgical procedure of a 35
      year-old patient presenting with discogenic lower back pain treated with an
      anterior lumbar interbody fusion and total disc replacement procedure to
      highlight the clinical advantages of intraoperative CT spinal navigation for
      accurate implant placement, therefore optimising peri- and post-operative
      outcomes.

PMID- 28744506
TI  - Different operative findings of cases predicted to be symptomatic discal
      pseudocysts after percutaneous endoscopic lumbar discectomy.
AB  - Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive
      treatment for lumbar disc herniation (LDH). This report focused on one of the
      rare complications of PELD: symptomatic postoperative discal pseudocyst (PDP). A
      27-year-old male patient (case 1) presented with recurrent radiculopathy in his
      left leg. Twenty days previously, he had undergone PELD for left L4/5 LDH and his
      symptoms temporarily improved. A 14-year-old female patient (case 2) also
      developed recurrent pain in her left leg. Thirty days previously, she had
      undergone PELD for left L4/5 LDH and her symptoms disappeared. On the basis of
      the finding of an expandable round lesion at the evacuated sites of LDH on
      magnetic resonance imaging (MRI), with low intensity of T1-weighted imaging and
      high intensity on T2-weighted imaging, we predicted symptomatic PDP in both
      cases. Given the progressive leg pain in both cases, surgical treatments were
      adopted (case 1: microendoscopic discectomy, case 2: PELD). During the operation,
      we confirmed that case 1 was a simple recurrence of LDH and case 2 was
      symptomatic PDP. Previous studies on symptomatic PDP included cases diagnosed
      without operative findings. Therefore, it should be carefully considered that
      such cases might be a simple recurrence of LDH.

PMID- 28744507
TI  - Minimally invasive fully endoscopic two-level posterior cervical foraminotomy:
      technical note.
AB  - Posterior cervical foraminotomy is an effective surgical treatment method for
      relieving radicular symptoms that result from cervical nerve root compression.
      Minimally invasive techniques and tubular retractor systems are available to
      minimize tissue retraction, but minimally invasive approaches can carry with them
      the surgical challenge of trying to pass instruments through a long narrow
      retractor that is also the port for visualizing the surgical pathology. Herein,
      the authors present a case of a 65-year-old man who presented with symptoms of a
      left C6 and C7 radiculopathy and left C5-6 and left C6-7 foraminal narrowing on
      MRI. A minimally-invasive fully endoscopic left C5-6 and C6-7 posterior
      foraminotomy was performed through a 1cm outer diameter working channel
      endoscopic with a 6 mm working channel. Clinicians should be aware that new
      minimally invasive non-fusion approaches for the treatment of cervical
      radiculopathy that utilize endoscopic visualization are now coming into use in
      clinical practice.

PMID- 28744508
TI  - Streptococcus intermedius: an unusual cause of spinal epidural abscess.
AB  - Spinal epidural abscess (SEA) following dental procedures is a rarely reported
      entity. Here, we present a unique case of a 74-year-old immunocompetent man who
      developed severe lower back pain and bilateral lower extremity weakness 4 days
      following two root canal procedures. Lumbar spine magnetic resonance imaging
      (MRI) showed several pockets of epidural abscesses extending from L1 through L5.
      Blood cultures grew Streptococcus intermedius, an anaerobic commensal bacterium
      of the normal flora of the mouth and upper airways. The patient was treated with
      IV penicillin for 7 days but his symptoms continued to deteriorate. A repeat MRI
      showed extension of the epidural abscess to T10-T11 level. The patient was
      emergently transferred to our hospital where he underwent bilateral decompressive
      laminectomy of T10 through S1 and abscess evacuation. Pus culture was positive
      for Streptococcus intermedius, which confirmed the diagnosis and the treatment
      plan. He was discharged on intravenous (IV) penicillin for 6 weeks. His symptoms
      improved significantly postoperatively as he retained his baseline strength in
      his lower extremity.

PMID- 28744509
TI  - Epithelioid hemangioendothelioma of the spine: case report and review of the
      literature.
AB  - Epithelioid hemangioendothelioma (EHE) has been described as a rare vascular bone
      lesion with histological features between hemangioma and high-grade angiosarcoma.
      Spinal EHE is a quite rare disease with few case reports and series reported in
      the literature. The tumor cells are positive for vimentin, CD31and CD34, factor
      VIII related antigen, ERG, and FLI1. Radiological features are not specific; it
      may appear as an osteolytic lesion. It can present as a multifocal disease in 40%
      of cases. No clear correlation with age and sex; however, it is slightly more
      common in males. Focal neck or back pain is the most common presenting symptom.
      The natural history of spinal EHE is unpredictable, and currently, there is no
      standard of care for treatment. Treatment options include preoperative
      embolization, and surgical resection followed by radiotherapy and/or
      chemotherapy. A 34-year-old previously healthy male presented with mid-thoracic
      back pain. Magnetic resonance imaging (MRI) of the spine revealed a decrease in
      vertebral body height at T5 with an enhancing mass. He underwent T5 balloon
      kyphoplasty and needle vertebral body biopsy. Results of the biopsy samples were
      non-diagnostic. Approximately 3 months after surgery, the patient presented with
      unsteady gait. A subsequent MRI revealed progression of the T5 compression
      fracture with cord compression. The patient subsequently underwent T4-T6
      bilateral posterior decompression for epidural tumor and T3-T7 posterior
      instrumentation with pedicle screws. Pathology of the lesion revealed EHE. The
      patient was started on local radiation therapy (RT). On follow-up, 3 months after
      the second surgery, the thoracic spinal pain had improved dramatically. Our
      review highlights the diagnosis, clinical presentation, and treatment of spinal
      EHE. Complete resection is associated with good outcome. Radiotherapy has been
      used in partially resected lesions. However, the role of radiotherapy as primary
      treatment is not yet defined. Further studies should develop a treatment
      algorithm for this rare tumour.

PMID- 28744510
TI  - Contralateral facet-sparing sublaminar endoscopic foraminotomy for the treatment
      of lumbar lateral recess stenosis: technical note.
AB  - Lumbar lateral recess stenosis that results from a degenerative bulging of the
      disc and overgrowth of the facet is a very common cause for lumbar radiculopathy
      in the elderly. The standard surgical treatment for symptomatic lumbar lateral
      recess stenosis often requires a laminectomy or hemi-laminectomy and medial
      facetectomy which can further destabilize a pathological motion segment. The
      authors present here a novel technique for contralateral endoscopic access to the
      lateral recess pathology that is truly minimally invasive and spares most of the
      facet joint complex: 6 patient cases are described where lateral recess stenosis
      pathology was accessed from a contralateral sublaminar endoscopic approach.

PMID- 28744511
TI  - Sublaminar wire migration into the medulla oblongata: a case report.
AB  - Atlantoaxial procedures have been developed in an effort to ensure solid C1-C2
      fusion. However, techniques that involve sublaminar wiring have the potential for
      neural structure injury. We present the management of a patient who previously
      underwent Gallie fusion 10 years ago and is presenting with a dislodged titanium
      wire that has migrated into the medulla oblongata. A 52-year-old female patient
      known with rheumatoid arthritis presented with truncal ataxia and food
      regurgitation 10 years after undergoing a C1-C2 Gallie fusion. A computerized
      tomography (CT) scan revealed that a wire from her Gallie fusion procedure
      migrated into the medulla oblongata. The patient underwent foramen magnum
      decompression with C1 bilateral laminectomy, instrumentation, and removal of a
      migrated wire. Six months later, a CT scan showed that all occipital screws were
      pulled out. In the revision surgery, new occipital screws were placed with a
      resultant significant improvement in patient's gait postoperatively. Wire
      migration as a differential diagnosis should be considered in patients presenting
      with neurological dysfunction who underwent surgical treatment with sublaminar
      wire fusion techniques.

PMID- 28744512
TI  - Unusual delayed presentation of superior mesenteric artery syndrome following
      scoliosis correction surgery-a case report and review of literature.
AB  - Superior mesenteric artery (SMA) syndrome secondary to extrinsic compression of
      third part of duodenum is an uncommon complication following scoliosis surgery.
      It is imperative to diagnose this presentation at an earlier stage as it can be a
      potentially life threatening complication. If the diagnosis is missed or delayed,
      the mortality rate can be as high as 33% due to fatal complications like
      aspiration pneumonia, acute gastric rupture and cardiovascular collapse. We
      present a 13-year-old patient who was diagnosed with SMA syndrome in the late
      post-operative period (5.1 weeks) following scoliosis correction surgery. A
      barium meal and follow-through confirmed the diagnosis of SMA syndrome. She was
      managed conservatively with which she recovered uneventfully. Such late
      presentations are very uncommon. In addition, we have also briefly reviewed the
      pertinent literature. It is essential that we identify high risk patients
      preoperatively so that we could optimize them with proper intensive dietary
      supplementation. Postoperatively, a high index of suspicion needs to be retained
      to identify this syndrome at an early stage so that conservative management may
      be initiated with good clinical outcome. SMA syndrome can be potentially life
      threatening when the diagnosis is missed or delayed.

PMID- 28744513
TI  - Minimally invasive endoscopic spinal cord untethering: case report.
AB  - Tethered cord syndrome is a constellation of symptoms and signs that include back
      and leg pain, bowel and bladder dysfunction, scoliosis and lower extremity
      weakness and deformity. Tethering may be due to a tight filum terminale or a form
      of spinal dysraphism. The authors present a case of a 40-year-old man who
      presented with symptoms of back pain, bilateral lower extremity radicular pain,
      and bowel and bladder dysfunction. Magnetic resonance imaging showed a sacral
      lipomyelomeningocele, with fat tracking superiorly to the conus, which was
      tethered at the L4-L5 level. A minimally-invasive surgical approach with
      endoscopic visualization and identification of the nerve roots and filum
      terminale was performed. The patient's postoperative clinical course was
      uneventful. This case highlights two important issues. First, minimally invasive
      spine techniques should be considered in the surgical treatment of tethered cord
      especially given the theoretical advantages of minimizing pain, spinal fluid
      leakage, and subsequent scarring. And second, endoscopic techniques are
      advancing. In the case presented here, endoscopic visualization and operative
      techniques made identification and transection of the filum terminale possible
      through a tiny dural opening. The small dural opening could theoretically pose
      the advantage of decreasing the risk of spinal fluid leakage. Clinicians should
      be aware that endoscopic visualization and techniques can serve as minimally
      invasive adjuncts to enhance the traditional approach to many surgical
      pathologies.

PMID- 28744514
TI  - Does sitting versus standing radiographic assessment of odontoid fractures
      matter? A case report.
AB  - Fractures of the odontoid are the most common cervical spine injury in the
      geriatric population. The relationship between odontoid fracture displacement and
      postural change has not been previously described. We present the first described
      case of an elderly female patient with thoracic kyphosis and a type II odontoid
      fracture demonstrating significant fracture displacement with a postural change
      from sitting to standing. Various radiographic parameters are assessed and
      discussed in an attempt to characterize and explain this finding. We highlight
      the importance of regional and global spinal alignment and quantify physiologic
      odontoid fracture behavior with postural changes in this growing demographic.
      Upright radiographs in both sitting and standing positions may be considered when
      concern for odontoid fracture stability is questioned.

PMID- 28744515
TI  - Solitary vertebral metastasis of primary clear cell carcinoma of the liver: a
      case report and review of literature.
AB  - Primary clear cell carcinoma of liver (PCCCL) is an uncommon variant of primary
      hepatocellular carcinoma. Though the literature describes a better prognosis in
      relation to the proportion of clear cells in the tumour when compared to the
      other variants, there is no general consensus in the management due to its rarity
      and unclear clinicopathological and prognostic factors. There is dearth of
      evidence with regard to the metastasizing nature of PCCCL and its management. In
      addition, the management of recurrent spinal tumours both primary and metastatic
      is not clear as the available evidence is mostly based on case reports. We
      describe an unusual presentation of PCCCL with solitary spinal metastasis and
      further complicated by tumour recurrence in a 71-year-old male. Such presentation
      has never been described before. He presented with low back pain and incomplete
      neurological deficits involving both lower limbs. On detailed evaluation, he was
      found to have a solitary metastasis at L3 vertebra secondary to PCCCL. He
      underwent radical excision of tumour and reconstruction for the solitary
      metastasis at L3 vertebral body and trans arterial chemo embolisation (TACE) for
      the hepatic lesion. Pt was asymptomatic until 9 months post operatively when he
      developed tumour recurrence at L3 vertebra. Patient subsequently underwent 2
      stage palliative surgery followed by radiotherapy and chemotherapy. At his latest
      follow-up (1 year), the patient's overall general condition has improved with
      residual neurological deficits in the lower limb. PCCCL is a rare type of
      hepatocellular carcinoma which can present as "solitary metastasis" to the spine.
      Although the literature suggests a good prognosis for this histological type,
      this case did not have a good outcome. In addition to providing information for
      the management of similar cases in the future, this case report highlights that
      every patient has to be managed on a case-by-case basis.

PMID- 28744516
TI  - Thoracic juxtafacet cyst (JFC): a cause of spinal myelopathy.
AB  - Spinal cord compression due to synovial facet cyst in thoracolumbar spine is
      rare. Several etiologies of juxtafacet cysts (JFCs) in this location have been
      discussed, particularly overload of the arthritic facet joints. Due to the narrow
      caliber of the thoracic spine, JFC in this location can present with radicular
      pain or progressive myelopathy. We report an interesting case of a 67 year-old
      woman who presented with the signs and symptoms of thoracic myelopathy. A left
      sided T11/12 JFC was identified on MRI and CT scans correlating with her
      myelopathy. She experienced a substantial improvement in her myelopathic symptoms
      after surgical excision of the JFC. The presentation, etiology, and therapeutic
      aspects of JFC are discussed in detail.

PMID- 28744517
TI  - C5 palsy after insertion of a winged expandable cervical cage: a case report and
      literature review.
AB  - C5 nerve root palsy is a well-known complication after anterior or posterior
      cervical decompression. Many theories have been proposed but the etiology is
      still unclear. The use of a winged expandable cage after single or multiple
      corpectomy is among the used techniques in reconstructing the cervical spine.
      Herein we report a case of C5 palsy after a three-level corpectomy and
      reconstruction using this device for the treatment of cervical spondylosis. In
      our case the preexisting foraminal stenosis, wide anterior decompression and
      partial improvement of cervical alignment were factors supposed contributing to
      the palsy.

PMID- 28744518
TI  - A case of cervical tuberculosis with severe kyphosis treated with a winged
      expandable cage after double corpectomy.
AB  - In this case report, we demonstrate that the use of a winged expandable cage was
      able to obtain good clinical and radiological results in a case of cervical
      tuberculosis with severe kyphosis. However, case series will be necessary to
      affirm its validity as a stand-alone device for similar cases with high risk of
      instability.

PMID- 28744519
TI  - Vertebral hemangiomas: common lesions with still many unknown aspects.

PMID- 28744520
TI  - Revealing the secret life of pre-implantation embryos by time-lapse monitoring: A
      review.
AB  - High implantation success following in vitro fertilization cycles are achieved
      via the transfer of embryos with the highest developmental competence. Multiple
      pregnancies as a result of the transfer of several embryos per cycle accompany
      with various complication. Thus, single-embryo transfer (SET) is the preferred
      practice in assisted reproductive technique (ART) treatment. In order to improve
      the pregnancy rate for SET, embryologists need reliable biomarkers to aid their
      selection of embryos with the highest developmental potential. Time-lapse
      technology is a noninvasive alternative conventional microscopic assessment. It
      provides uninterrupted and continues the survey of embryo development to transfer
      day. Today, there are four time-lapse systems that are commercially available for
      ART centers. In world and Iran, the first time lapse babies were born in 2010 and
      2015, respectively, conceived by SET. Here, we review the use of time-lapse
      monitoring in the observation of embryogenesis as well as its role in SET.
      Although, the findings from our review support common use of time-lapse
      monitoring in ART centers; but, future large studies assessing this system in
      well-designed trials are necessary.

PMID- 28744521
TI  - Protective effects of melatonin and ghrelin on spermatogenesis: A narrative
      review of the literature.
AB  - Spermatocytogenesis starts from lumens of seminiferous cords and after migration
      to the basal membrane ends to the lumens again. We attempt to review the
      protective effects of melatonin and ghrelin on Spermatocytogenesis and in
      particular on spermatogonial stem cells, as two rather newly-discovered hormones.
      Testicular freezing prior to chemotherapy and radiotherapy is one of the ways of
      preserving fertility in children with cancer. The freezing has two methods of
      slow-freezing (cryopreservation) and rapid-freezing (vitrification).
      Administration of melatonin can maintain the quality of the germ cells underwent
      such processes, as well as ghrelin, can protect germ cells from the toxicities
      secondary to ischemic injuries, and pathologic apoptosis. This review indicates
      that in vitro or in vivo administration of melatonin or ghrelin, could be
      effective to preserve fertilization and also they can be used in assisted
      reproductive technologies to improve the quality of sperms. Future original
      studies should be propelled toward human studies, of course with observing the
      ethics.

PMID- 28744522
TI  - The effects of multi mineral-vitamin D and vitamins (C+E) supplementation in the
      prevention of preeclampsia: An RCT.
AB  - BACKGROUND: Several studies have reported the uncertain role of multi-minerals
      and vitamins in the prevention of preeclampsia. OBJECTIVE: The present study aims
      to investigate the effect of multimineral-vitamin D supplements (calcium,
      magnesium, zinc and Vitamin D) and vitamins (C+ E) in the prevention of
      preeclampsia. MATERIALS AND METHODS: In this randomized clinical trial, 90
      pregnant women were divided into three groups: group A received Ferrous sulfate
      (1 tablet/day) + one tablet of Claci-care multimineral-vitamin D containing 800mg
      calcium, 200mg magnesium, 8mg zinc and 400 IU Vitamin D3 per day; group B
      received Ferrous sulfate (1 tablet/day) + 250 mg vitamin C + 55 mg vitamin E; and
      the controls received only one Ferrous sulfate tablet daily. RESULTS: The
      incidence of preeclampsia in group A was significantly lower than the control
      group (p=0.03), while there was no significant difference between group B and
      controls (p=0.50), as well as groups A and B (p=0.063). The incidence of neonatal
      complications in the group A was significantly lower than the control group
      (p=0.01), while there was no significant difference between group B and control
      (p=0.48). CONCLUSION: According to the results, calcium, magnesium, and zinc
      supplements have a significant effect on the prevention of preeclampsia. In
      addition, prescription of multimineral-vitamin D during pregnancy can be a low
      cost and affordable way to reduce the incidence of preeclampsia in women who are
      at high risk of preeclampsia.

PMID- 28744523
TI  - Evaluation of intracellular anion superoxide level, heat shock protein A2 and
      protamine positive spermatozoa percentages in teratoasthenozoospermia.
AB  - BACKGROUND: Teratoasthenozoospermia (TA) is a severe form of male infertility
      with no clear etiology. OBJECTIVE: To compare the level of intracellular anion
      superoxide (O2-), heat shock protein A2 (HSPA2) and protamine deficiencies in
      ejaculated spermatozoa between teratoasthenozoospermic and normozoospermic men.
      MATERIALS AND METHODS: In this case- control study, semen samples of 20 infertile
      men, with TA (with normal morphology lower than 4%_ and total motility lower than
      40% ) as the case group and 20 normozoospermic fertile men as the control group
      were evaluated for intracellular O2- and HSPA2 by flow cytometry and protamine
      deficiency by Chromomycin A3 (CMA3) test. RESULTS: The rate of CMA3+ spermatozoa
      in the case group was higher than controls (p=0.001). The percentages of HSPA2+
      spermatozoa in the cases were significantly lower than controls (p=0.001). Also,
      intracellular O2- levels in the case group were significantly higher than
      controls (p=0.001) and had positive correlations with sperm apoptosis (r=0.79,
      p=0.01) and CMA3 positive sperm (r=0.76, p=0.01), but negative correlations with
      normal morphology (r=-0.81, p=0.01) and motility (r=-0.81, p=0.01). There was no
      significant correlation between intracellular O2- and HSPA2 in the case group
      (r=0.041, p=0.79). CONCLUSION: We suggest that the increase in intracellular O2-,
      decrease in spermatozoa HSPA2+, and high percentages of spermatozoa with immature
      chromatin might be considered as etiologies of infertility in TA patients.

PMID- 28744524
TI  - Evaluating the factor structure, item analyses, and internal consistency of
      hospital anxiety and depression scale in Iranian infertile patients.
AB  - BACKGROUND: The hospital anxiety and depression scale (HADS) is a common
      screening tool designed to measure the level of anxiety and depression in
      different factor structures and has been extensively used in non-psychiatric
      populations and individuals experiencing fertility problems. OBJECTIVE: The aims
      of this study were to evaluate the factor structure, item analyses, and internal
      consistency of HADS in Iranian infertile patients. MATERIALS AND METHODS: This
      cross-sectional study included 651 infertile patients (248 men and 403 women)
      referred to a referral infertility Center in Tehran, Iran between January 2014
      and January 2015. Confirmatory factor analysis was used to determine the
      underlying factor structure of the HADS among one, two, and three-factor models.
      Several goodness of fit indices were utilized such as comparative, normed and
      goodness of fit indices, Akaike information criterion, and the root mean squared
      error of approximation. In addition to HADS, the Satisfaction with Life Scale
      questionnaires as well as demographic and clinical information were administered
      to all patients. RESULTS: The goodness of fit indices through CFAs exposed that
      three and one-factor model provided the best and worst fit to the total, male and
      female datasets compared to the other factor structure models for the infertile
      patients. The Cronbach's alpha for anxiety and depression subscales were 0.866
      and 0.753 respectively. The HADS subscales significantly correlated with SWLS,
      indicating an acceptable convergent validity. CONCLUSION: The HADS was found to
      be a three-factor structure screening instrument in the field of infertility.

PMID- 28744525
TI  - Frequency of chromosomal aneuploidy in high quality embryos from young couples
      using preimplantation genetic screening.
AB  - BACKGROUND: Selection of the best embryo for transfer is very important in
      assisted reproductive technology (ART). Using morphological assessment for this
      selection demonstrated that the correlation between embryo morphology and
      implantation potential is relatively weak. On the other hand, aneuploidy is a key
      genetic factor that can influence human reproductive success in ART. OBJECTIVE:
      The aim of this lab trial study was to evaluate the incidence of aneuploidies in
      five chromosomes in the morphologically high-quality embryos from young patients
      undergoing ART for sex selection. MATERIALS AND METHODS: A total of 97 high
      quality embryos from 23 women at the age of 37or younger years that had
      previously undergone preimplantation genetic screening for sex selection were
      included in this study. After washing, the slides of blastomeres from embryos of
      patients were reanalyzed by fluorescence in-situ hybridization for chromosomes
      13, 18 and 21. RESULTS: There was a significant rate of aneuploidy determination
      in the embryos using preimplantation genetic screening for both sex and three
      evaluated autosomal chromosomes compared to preimplantation genetic screening for
      only sex chromosomes (62.9% vs. 24.7%, p=0.000). The most frequent detected
      chromosomal aneuploidy was trisomy or monosomy of chromosome 13. CONCLUSION:
      There is considerable numbers of chromosomal abnormalities in embryos generated
      in vitro which cause in vitro fertilization failure and it seems that
      morphological characterization of embryos is not a suitable method for choosing
      the embryos without these abnormalities.

PMID- 28744526
TI  - Relative frequency of human papillomavirus genotypes and related sociodemographic
      characteristics in women referred to a general hospital in Tehran, 2014-2015: A
      cross-sectional study.
AB  - BACKGROUND: Human papilloma virus (HPV) is one of the major public health
      problems and the main causes of cervical cancer. The prevalence HPV infection in
      developing countries with low financial resources is high. OBJECTIVE: This study
      aimed to determine the relative frequency of HPV genotypes and its
      sociodemographic characteristics in women referred to a general hospital in
      Tehran, Iran from 2014-2015. MATERIALS AND METHODS: This cross-sectional study
      was performed in 400 women with Pap smear samples, referring to to a general
      hospital in Tehran, Iran from 2014-2015. The detection of 28 HPV genotypes was
      performed by using the Multiplex PCR technique. The sociodemographic survey was
      conducted for each HPV positive woman. RESULTS: HPV-positive infection was
      detected in 155 (38.75%) women aged 17-85 years. HPV 16 (19.1%) was the most
      prevalent type, followed by HPV 39 (12.5%) and HPV 18 (8.9%). The highest rate of
      HPV infection was observed at the age of 36 years (7.7%). The level of education
      and economic situation of each woman were showed most of HPV-positive women had a
      high school diploma (34.6%) and average economic situation (67,9%). 60.9% of
      these women were a housewife, and 67.3% lived in the capital . CONCLUSION:
      Determination of HPV genotype and risk factor related to HPV infection in each
      geographical region can lead to the production of effective vaccines against the
      HPV virus. It can also be useful for disease management and high sensitivity
      diagnosis of cervical intraepithelial neoplasia.

PMID- 28744527
TI  - Design and characterization of hydrogel nanoparticles with tunable network
      characteristics for sustained release of a VEGF-mimetic peptide.
AB  - Peptides that mimic the bioactivity of growth factors are rapidly emerging as
      therapeutics for a variety of drug delivery applications including therapeutic
      neovascularization. Neovascularization requires controlled and sustained delivery
      of proangiogenic factors to stimulate reperfusion of ischemic tissues. To this
      end, hydrogel nanoparticles were designed to provide sustained and tunable
      diffusion-based release of a pro-angiogenic peptide, QK. Inverse phase mini
      emulsion polymerization (IPMP) was used to generate crosslinked poly(ethylene)
      glycol (PEG) hydrogel nanoparticles entrapped with the QK peptide. Peptide
      release kinetics were tuned through adjustments in nanoparticle crosslink
      density. This was achieved by altering the mole fraction of the crosslinking
      agent which allowed for the synthesis of low crosslink density (0.754 mmol cm-3)
      and high crosslink density (0.810 mmol cm-3) nanoparticles. Nanoparticle tracking
      analysis revealed narrow particle size distributions and similar particle sizes
      regardless of crosslink density (225 +/- 75 nm and 233 +/- 73 nm, for low and
      high crosslink density nanoparticles, respectively). The zeta potential was found
      to be -26 mV for blank nanoparticles and +4 mV in the case of QK-loaded
      nanoparticles. The resulting nanoparticle crosslink density impacted both peptide
      loading as well as release kinetics. In terms of cumulative fractional release
      and weight of peptide released per mass of nanoparticle, higher crosslink density
      nanoparticles resulted in slower peptide release kinetics. The IPMP process
      preserved the QK secondary structure and its bioactivity as confirmed using
      circular dichroism spectroscopy and a Matrigel tubulogenesis assay, respectively,
      with released peptide. The presented nanoparticles hold great potential for use
      as drug delivery carriers for stimulation of therapeutic neovascularization of
      ischemic tissues.

PMID- 28744528
TI  - Copper-catalyzed trifluoromethylazidation and rearrangement of aniline-linked 1,7
      enynes: access to CF3-substituted azaspirocyclic dihydroquinolin-2-ones and
      furoindolines.
AB  - A set of reactions involving copper-catalyzed trifluoromethylazidation and then
      rearrangement of aniline-linked 1,7-enynes with the relatively poorly reactive
      Togni reagent I and TMSN3 was developed, and provided facile access to
      structurally diverse and useful CF3-substituted azaspirocyclic dihydroquinolin-2
      ones bearing two adjacent quaternary carbon centers. We were also able to obtain
      these products on a large scale. Moreover, the obtained products were further
      transformed into a range of synthetically valuable furoindolines bearing three
      consecutive quaternary carbon centers after reduction by NaBH4. Also, the
      delivery of multi-functionalized aziridines as a result of alcoholysis and LiAlH4
      reduction of corresponding dihydroquinolin-2-ones 2ba demonstrated the synthetic
      value of this newly developed protocol.

PMID- 28744529
TI  - Direct monitoring of lipid transfer on exposure of citrem nanoparticles to an
      ethanol solution containing soybean phospholipids by combining synchrotron SAXS
      with microfluidics.
AB  - Lipid exchange among citrem nanoparticles and an ethanol micellar solution
      containing soy phosphatidylcholine was investigated in situ by coupling small
      angle X-ray scattering with a microfluidic device. The produced soy
      phosphatidylcholine/citrem nanoparticles have great potential in the development
      of hemocompatible nanocarriers for drug delivery.

PMID- 28744530
TI  - Enzyme-free, signal-amplified nucleic acid circuits for biosensing and bioimaging
      analysis.
AB  - Enzyme-free, signal-amplified nucleic acid circuits utilize programmed assembly
      reactions between nucleic acid substrates to transduce a chemical input into an
      amplified detection signal. These circuits have shown great potential for
      developing biosensors for high-sensitivity and high-selectivity detection of
      varying targets including nucleic acids, small molecules and proteins in vitro
      and for high-contrast in situ visualization and imaging of these targets in
      tissues and living cells. We review the background of the enzyme-free, signal
      amplified nucleic acid circuits, including their mechanism, significance, types
      and development. We also review current applications of these circuits for
      biosensors and bioimaging.

PMID- 28744531
TI  - Flow-induced nanostructuring of gelled emulsions.
AB  - Although the phase behavior of emulsions has been thoroughly investigated, the
      effect of flow on emulsion morphology, which is relevant for many applications,
      is far from being fully elucidated. Here, we investigate an emulsion based on two
      common nonionic surfactants in a range of water concentration where complex and
      diverse microstructures are found at rest, such as multilamellar and bicontinuous
      phases. In spite of such complexity, once subjected to shear flow, all the
      emulsions investigated are characterized by thinning filaments which eventually
      break up into a concentrated suspension of micro-sized water-based droplets
      dispersed in a continuous oil phase. The so-formed droplets tend to align in
      string-like structures. The emulsions exhibit a yield stress, whose value can be
      estimated by the plug-core velocity profiles in pressure-driven capillary flow,
      thus providing evidence of weakly attractive interdroplet interactions. The
      latter are consistent with droplet clustering and percolation observed at rest.
      These results can also be relevant to the flow behavior of other liquid-liquid
      systems, such as polymer blends, where the flow-induced microstructure is under
      debate as well.

PMID- 28744532
TI  - Oxidation-induced C-H amination leads to a new avenue to build C-N bonds.
AB  - In this work, we develop an oxidation-induced C-H functionalization strategy,
      which not only leads to a new avenue to build C-N bonds, but also leads to
      different site-selectivity compared with "classic directing-groups". The high
      selectivity of our new catalytic system originates from the heterogeneous
      electron-density distribution of the radical cation species which are induced by
      single electron transfer between the aromatics and oxidant-Cu(ii) species.

PMID- 28744533
TI  - Synergistic therapy of chemotherapeutic drugs and MTH1 inhibitors using a pH
      sensitive polymeric delivery system for oral squamous cell carcinoma.
AB  - MutT homolog 1 (MTH1) is an essential sanitizer of the free nucleotide pool that
      prevents lethal DNA damage in cancer cells, which has been validated as an
      anticancer target in recent years. Small molecule TH287 potently and selectively
      inhibits the MTH1 protein in cells. Here, we developed an effective
      chemotherapeutic system for oral squamous cell carcinoma (OSCC) based on
      polymeric nanoparticles that achieve co-delivery of anticancer drug sodium
      arsenite (NaAsO2) and MTH1 inhibitor TH287. Cationic hyperbranched poly(amine
      ester) (HPAE), an amphiphilic and pH-sensitive polymer with a highly branched
      structure, self-assembled into nanoparticles in aqueous solution. Both NaAsO2 and
      TH287 could be loaded into HPAE nanoparticles with the help of electrostatic
      attraction and hydrophobic interaction. The release of NaAsO2 and TH287 from
      HPAE(NaAsO2 + TH287) nanoparticles was pH-dependent. In vitro evaluation
      demonstrated that the HPAE(NaAsO2 + TH287) nanoparticles rapidly entered cancer
      cells and released NaAsO2 and TH287 in response to acidic intracellular
      environments. In comparison with NaAsO2, TH287, HPAE(NaAsO2) nanoparticles,
      HPAE(TH287) nanoparticles, and the physical mixture of HPAE(NaAsO2) nanoparticles
      and TH287, the HPAE(NaAsO2 + TH287) nanoparticles exhibited more effective
      inhibition of tumor cell proliferation, illustrating the synergistic effect of
      NaAsO2 and TH287. The experimental results show that TH287 is likely to inhibit
      MTH1 in tumor cells, rendering them more sensitive to NaAsO2.

PMID- 28744534
TI  - A surface plasmon field-enhanced fluorescence reversible split aptamer biosensor.
AB  - Surface plasmon field-enhanced fluorescence is reported for the readout of a
      heterogeneous assay that utilizes low affinity split aptamer ligands. Weak
      affinity ligands that reversibly interact with target analytes hold potential for
      facile implementation in continuous monitoring biosensor systems. This
      functionality is not possible without the regeneration of more commonly used
      assays relying on high affinity ligands and end-point measurement. In
      fluorescence-based sensors, the use of low affinity ligands allows avoiding this
      step but it imposes a challenge associated with the weak optical response to the
      specific capture of the target analyte which is also often masked by a strong
      background. The coupling of fluorophore labels with a confined field of surface
      plasmons is reported for strong amplification of the fluorescence signal emitted
      from the sensor surface and its efficient discrimination from the background.
      This optical scheme is demonstrated for time-resolved analysis of chosen model
      analytes - adenoside and adenosine triphosphate - with a split aptamer that
      exhibits an equilibrium affinity binding constant between 0.73 and 1.35 mM. The
      developed biosensor enables rapid and specific discrimination of target analyte
      concentration changes from low MUM to mM in buffer as well as in 10% serum.

PMID- 28744535
TI  - Core and surface microgel mechanics are differentially sensitive to alternative
      crosslinking concentrations.
AB  - Microgel mechanics are central to the swelling of stimuli-responsive materials
      and furthermore have recently emerged as a novel design space for tuning the
      uptake of nanotherapeutics. Despite this importance, the techniques available to
      assess mechanics, at the sub-micron scale, remain limited. In this report, all
      mechanical moduli for a series of air-dried, polystyrene-co-poly(N
      isopropylacrylamide) (pS-co-NIPAM) microgels of varying composition in monomer
      and crosslinker (N,N'-methylene-bisacrylamide (BIS)) mol% have been determined
      using Brillouin light scattering (BLS) and AFM nanoindentation. These techniques
      sample the material through distinct means and provide complementary
      nanomechanical data. An initial demonstration of this combined approach is used
      to evaluate size-dependent nanomechanics in pS particles of varying diameter. For
      the pS-co-NIPAM series, our BLS results demonstrate an increase in Young's (E)
      and shear moduli with increasing NIPAM and/or BIS mol%, while the Poisson's ratio
      decreased. The same rank order in E was observed from AFM and the two techniques
      correlate well. However, at low BIS crosslinking, an inverted particle structure
      persists and small increases in BIS yield a higher increase in E from AFM
      relative to BLS, consistent with a higher density at the particle surface. At
      higher BIS incorporation, the microgel reverts to a typical, dense-core structure
      and further increasing BIS yields changes to core-particle mechanics reflected in
      BLS. Lastly, at 75 mol% NIPAM, the microgels displayed a broad volume phase
      transition and increased crosslinking resulted in a minor, yet unexpected,
      increase in swelling ratio. This complementary approach offers new insight into
      nanomechanics critical for microgel design and application.

PMID- 28744536
TI  - Chevrons, filaments, spinning clusters and phase coexistence: emergent dynamics
      of 2- and 3-d particle suspensions driven by multiaxial magnetic fields.
AB  - In recent years a rich variety of emergent phenomena have been observed when
      suspensions of magnetic particles are subjected to alternating magnetic fields.
      These particle assemblies often exhibit vigorous dynamics due to the injection of
      energy from the field. These assemblies include surface and interface phenomena,
      such as highly organized, segmented "snakes" that can be induced to swim by
      structural symmetry breaking, and "asters" and "anti-asters," particle assemblies
      that can be manipulated to capture and transport cargo. In bulk suspensions of
      magnetic platelets subjected to multiaxial alternating fields, advection lattices
      and even vortex lattices have been created, and a variety of biomimetic dynamics 
      serpents, bees and amoebas - have been discovered in magnetic fluids suspended
      in an immiscible liquid. In this paper several new driven phases are presented,
      including flying chevrons, dense spinning clusters, filaments, and examples of
      phase coexistence in driven phases. These observations broaden the growing field
      of driven magnetic suspensions and present new challenges to those interested in
      simulating the dynamics of these complex systems.

PMID- 28744537
TI  - Initiation of wetting, filmwise condensation and condensate drainage from a
      surface in a gravity field.
AB  - The zeta adsorption isotherm is based on the hypothesis that a vapour adsorbed on
      a solid surface consists of a collection of molecular clusters. We use this
      isotherm to propose a method for determining the wetting condition on a
      vertically oriented silicon surface exposed to heptane in a gravity field.
      Measurements indicate the amount adsorbed is larger at positions of smaller
      potential energy. The wetting condition is taken to be reached when the adsorbed
      vapour is transformed into the adsorbed liquid phase: adsorption lowers the
      surface tension of Si from the value in the absence of adsorption to that of
      liquid heptane at wetting, and then as the Si-heptane is cooled further it is
      reduced to zero, at a subcooling of 3.7 K. The expectation is that when this
      subcooling is reached, gravity would cause the larger molecular clusters to drain
      down the surface. This prediction is supported by experimental observations.

PMID- 28744538
TI  - Chiral phosphoric acid-catalyzed desymmetrizative glycosylation of 2
      deoxystreptamine and its application to aminoglycoside synthesis.
AB  - This work describes chiral phosphoric acid (CPA)-catalyzed desymmetrizative
      glycosylation of meso-diol derived from 2-deoxystreptamine. The chirality of CPA
      dictates the outcome of the glycosylation reactions, and the use of enantiomeric
      CPAs results in either C4-glycosylated (67 : 33 d.r.) or C6-glycosylated (86 : 14
      d.r.) 2-deoxystreptamines. These glycosylated products can be converted to
      aminoglycosides, and the application of this strategy to the synthesis of
      protected iso-neamine and iso-kanamycin B with inverted connection at the C4 and
      C6 positions is described.

PMID- 28744539
TI  - Drop-on-coilable-fibre systems exhibit negative stiffness events and transitions
      in coiling morphology.
AB  - We investigate the mechanics of elastic fibres carrying liquid droplets. In such
      systems, buckling may localize inside the drop cavity if the fibre is thin
      enough. This so-called drop-on-coilable-fibre system exhibits a surprising liquid
      like response under compression and a solid-like response under tension. Here we
      analyze this unconventional behavior in further detail and find theoretical,
      numerical and experimental evidence of negative stiffness events. We find that
      the first and main negative stiffness regime owes its existence to the transfer
      of capillary-stored energy into mechanical curvature energy. The following
      negative stiffness events are associated with changes in the coiling morphology
      of the fibre. Eventually coiling becomes tightly locked into an ordered phase
      where liquid and solid deformations coexist.

PMID- 28744540
TI  - Naphthalene amine support for G-quadruplex isolation.
AB  - G-quadruplex (G4) is involved in many biological processes, such as telomere
      function, gene expression and DNA replication. The selective isolation of G4
      using affinity ligands that bind tightly and selectively is a valuable strategy
      for discovering new G4 binders for the separation of G4 from duplexes or the
      discrimination of G4 structures. In this work, one affinity chromatographic
      support was prepared using a naphthalene amine as a G4 binder. The ligand was
      immobilized on epoxy-activated Sepharose CL-6B using a long spacer arm and was
      characterized by HR-MAS spectroscopy. The supercoiled (sc) isoform of pVAX1-LacZ
      and pVAX1-G4 was isolated from a native sample. Also, the recovery and isolation
      of the plasmid isoforms from Escherichia coli lysate samples were achieved using
      an ionic gradient with different concentrations of NaCl in 10 mM Tris-HCl (pH
      7.4). The retention times of different DNA/single strand sequences that can form
      G4, such as, c-MYC, c-kit1, c-kit2, tetrameric, telomeric (23AG), thrombin
      aptamer (TBA) and 58Sgamma3 in this support were evaluated. Our experimental
      results suggest that the support exhibits selectivity for parallel c-MYC and c
      kit1 G4s. In vitro transcription was performed using purified sc pVAX1-G4 and
      pPH600 to induce G4 formation and circular dichroism (CD) analysis confirmed that
      both transcripts adopt a parallel G4 topology.

PMID- 28744541
TI  - Silver-gold alloy nanoparticles as tunable substrates for systematic control of
      ion-desorption efficiency and heat transfer in surface-assisted laser
      desorption/ionization.
AB  - Systematically controlling heat transfer in the surface-assisted laser
      desorption/ionization (SALDI) process and thus enhancing the analytical
      performance of SALDI-MS remains a challenging task. In the current study, by
      tuning the metal contents of Ag-Au alloy nanoparticle substrates (AgNPs,
      Ag55Au45NPs, Ag15Au85NPs and AuNPs, ?: ~2.0 nm), it was found that both SALDI ion
      desorption efficiency and heat transfer can be controlled in a wide range of
      laser fluence (21.3 mJ cm-2 to 125.9 mJ cm-2). It was discovered that ion
      detection sensitivity can be enhanced at any laser fluence by tuning up the Ag
      content of the alloy nanoparticle, whereas the extent of ion fragmentation can be
      reduced by tuning up the Au content. The enhancement effect of Ag content on ion
      desorption was found to be attributable to the increase in laser absorption
      efficiency (at 355 nm) with Ag content. Tuning the laser absorption efficiency by
      changing the metal composition was also effective in controlling the heat
      transfer from the NPs to the analytes. The laser-induced heating of Ag-rich alloy
      NPs could be balanced or even overridden by increasing the Au content of NPs,
      resulting in the reduction of the fragmentation of analytes. In the correlation
      of experimental measurement with molecular dynamics simulation, the effect of
      metal composition on the dynamics of the ion desorption process was also
      elucidated. Upon increasing the Ag content, it was also found that phase
      transition temperatures, such as melting, vaporization and phase explosion
      temperature, of NPs could be reduced. This further enhanced the desorption of
      analyte ions via phase-transition-driven desorption processes. The significant
      cooling effect on the analyte ions observed at high laser fluence was also
      determined to be originated from the phase explosion of the NPs. This study
      revealed that the development of alloy nanoparticles as SALDI substrates can
      constitute an effective means for the systematic control of ion-desorption
      efficiency and the extent of heat transfer, which could potentially enhance the
      analytical performance of SALDI-MS.

PMID- 28744542
TI  - Competitive multicomponent anion exchange adsorption of proteins at the single
      molecule level.
AB  - We use single molecule spectroscopy to study a multicomponent, competitive
      protein adsorption system. Fluorescently-labeled alpha-lactalbumin proteins are
      super-resolved adsorbing to cationic anion-exchange ligands in the presence of a
      competitor, insulin. We find that the competitor reduces the number of binding
      events by blocking ligands throughout the observed measurement time while the
      single-site adsorption kinetics are unchanged.

PMID- 28744543
TI  - Entrapment of interfacial nanobubbles on nano-structured surfaces.
AB  - Spherical-cap-shaped interfacial nanobubbles (NBs) forming on hydrophobic
      surfaces in aqueous solutions have extensively been studied both from a
      fundamental point of view and due to their relevance for various practical
      applications. In this study, the nucleation mechanism of spontaneously generated
      NBs at solid-liquid interfaces of immersed nanostructured hydrophobic surfaces is
      studied. Depending on the size and density of the surface nanostructures, NBs
      with different size and density were reproducibly and deterministically obtained.
      A two-step process can explain the NB nucleation, based on the crevice model,
      i.e., entrapped air pockets in surface cavities which grow by diffusion. The
      results show direct evidence for the spontaneous formation of NBs on a surface at
      its immersion. Next, the influence of size and shape of the nanostructures on the
      nucleated NBs are revealed. In particular, on non-circular nanopits we obtain NBs
      with a non-circular footprint, demonstrating the strong pinning forces at the
      three-phase contact line.

PMID- 28744544
TI  - Impedance investigation of the highly efficient polymer solar cells with
      composite CuBr2/MoO3 hole transport layer.
AB  - Developing an air-stable, low-cost, non-toxic, and high-transparency charge
      buffer layer is a critical strategy to achieve the high photoelectric conversion
      efficiency of polymer photovoltaic cells. This paper reports the remarkable
      improvement of device performance by employing a combination of copper bromide
      (CuBr2) and molybdenum trioxide (MoO3) (CuBr2/MoO3) as the hole transport layer
      (HTL) of inverted-type polymer solar cells (PSCs). The bulk transport processes
      and resistive capacitance elements in the operating PTB7:PC71BM bulk
      heterojunction PSCs were characterized using impedance spectroscopy. The
      impedance response was modeled using two equivalent circuital models, which are
      the general transmission line circuit (GTLC) model and the electrochemical
      polarization model. The effective carrier lifetime, conductivity, and mobility
      for both devices were extracted from the models. The improved hole transport at
      the anode and the efficient electron transport blocking decreased interface
      recombination and contact resistance, resulting in improved power conversion
      efficiency (PCE) values ranging from 7.30% to 9.56%. These results suggest that
      quantitative interpretation and modeling of the impedance spectroscopy results
      provide an effective way to unravel the operating mechanism of photovoltaic
      devices.

PMID- 28744545
TI  - The correspondence between the conformational and chromophoric properties of
      amorphous conjugated polymers in mesoscale condensed systems.
AB  - For pi-conjugated polymers, the notion of spectroscopic units or "chromophores"
      provides illuminating insights into the experimentally observed
      absorption/emission spectra and the mechanisms of energy/charge transfer. To
      date, however, no statistical analysis has revealed a direct correspondence
      between chromophoric and conformational properties-with the latter being
      fundamental to polymer semiconductors. Herein, we propose a "persistence length"
      calculation to re-evaluate chain conformation over a full conjugation length. The
      mesoscale condensed systems of MEH-PPV and MEH-PPV/C60 hybrid (system size ~10 *
      10 * 10 nm3) are utilized as two prototypical model systems, along with a full
      range of segmental lengths (2-20-mer) and five lowest singlet excited states to
      hint at the generality of the features presented. We demonstrate, for the first
      time, that two properly re-defined conformational factors that characterize chain
      folding and planarity, respectively, capture excellently the population
      distribution of chromophores in both systems investigated. In contrast, the
      conventional strategy of utilizing two adjacent monomer units to characterize
      (local) chain conformation results in only an inconspicuous correlation between
      the two, as previously reported. It is further shown that chain folding-and not
      chain planarity-is more relevant in capturing the associated oscillator strength
      for the first excited state, where the transient dipole moments are known to
      align with the chain conformation, although the corresponding excitation energy
      and exciton size seem relatively unaffected. The observed effects of C60 on the
      MEH-PPV adsorption spectra also agree with recent experimental trends. Overall,
      the present findings are expected to aid future multiscale computer simulations
      and spectroscopy-data interpretations for polymer semiconductors and their hybrid
      systems.

PMID- 28744546
TI  - Distinct solvent- and temperature-dependent packing arrangements of anti-parallel
      beta-sheet polyalanines studied with solid-state 13C NMR and MD simulation.
AB  - Polyalanine (polyA) sequences are well known as the simplest sequence that
      naturally forms anti-parallel beta-sheets and constitute a key element in the
      structure of spider and wild silkworm silk fibers. We have carried out a
      systematic analysis of the packing of anti-parallel beta-sheets for (Ala)n, n =
      5, 6, 7 and 12, using primarily 13C solid-state NMR and MD simulation. HFIP and
      TFA are frequently used as the dope solvents for recombinant silks, and polyA was
      solidified from both HFIP and TFA solutions by drying. An analysis of Ala Cbeta
      peaks in the 13C CP/MAS NMR spectra indicated that polyA from HFIP was mainly
      rectangular but polyA from TFA was mainly staggered. The transition from the
      rectangular to the staggered arrangement in (Ala)6 was observed for the first
      time from the change in the Ala Cbeta peak through heat treatment at 200  degrees
      C for 4 h. The removal of the bound water was confirmed by thermal analysis. This
      transition could be reproduced by MD simulation of (Ala)6 molecules at 200 
      degrees C after removal of the bound water molecules. In this way, the origin of
      the stability of the different packing arrangements of polyA was clarified.

PMID- 28744547
TI  - Broad spectrum infrared thermal desorption of wipe-based explosive and narcotic
      samples for trace mass spectrometric detection.
AB  - Wipe collected analytes were thermally desorbed using broad spectrum near
      infrared heating for mass spectrometric detection. Employing a twin tube filament
      based infrared emitter, rapid and efficiently powered thermal desorption and
      detection of nanogram levels of explosives and narcotics was demonstrated. The
      infrared thermal desorption (IRTD) platform developed here used multi-mode
      heating (direct radiation and secondary conduction from substrate and subsequent
      convection from air) and a temperature ramp to efficiently desorb analytes with
      vapor pressures across eight orders of magnitude. The wipe substrate experienced
      heating rates up to (85 +/- 2)  degrees C s-1 with a time constant of (3.9 +/-
      0.2) s for 100% power emission. The detection of trace analytes was also
      demonstrated from complex mixtures, including plastic-bonded explosives and
      exogenous narcotics, explosives, and metabolites from collected artificial latent
      fingerprints. Manipulation of the emission power and duration directly controlled
      the heating rate and maximum temperature, enabling differential thermal
      desorption and a level of upstream separation for enhanced specificity.
      Transitioning from 100% power and 5 s emission duration to 25% power and 30 s
      emission enabled an order of magnitude increase in the temporal separation
      (single seconds to tens of seconds) of the desorption of volatile and semi
      volatile species within a collected fingerprint. This mode of operation reduced
      local gas-phase concentrations, reducing matrix effects experienced with high
      concentration mixtures. IRTD provides a unique platform for the desorption of
      trace analytes from wipe collections, an area of importance to the security
      sector, transportation agencies, and customs and border protection.

PMID- 28744548
TI  - XUV/X-ray light and fast ions for ultrafast chemistry.
AB  - The deposition of large amounts of energy in a molecule by XUV/X-ray photon
      absorption or fast-ion collision, triggers a set of complex ultrafast electronic
      and nuclear dynamics that allow a deep understanding and control of chemical
      reactivity. This themed issue showcases the research performed in the
      understanding, monitoring and control of these processes.

PMID- 28744549
TI  - Fit-to-Targets for the Desired Sensation Level Version 5.0a Hearing Aid
      Prescription Method for Children.
AB  - Purpose: The purpose of this study was to measure the range of fit to Desired
      Sensation Level version 5.0 (DSL v5.0) targets in pediatric practice
      environments. Results will be used in the future to develop clinical-aided speech
      intelligibility index typical performance data. Method: Clinical partners
      collected data from 161 final hearing aid settings for children aged <= 10 years.
      Measured data were obtained by performing 2-cm3 coupler-simulated real-ear
      measurements using the DSL v5.0 implementation on the Audioscan VF-1 (Etymonic
      Design Inc., Dorchester, ON, Canada) for soft, average, and loud speech inputs
      and maximum hearing aid output levels. Results: Fittings were within +/- 5-dB
      root-mean-square (RMS) error of target for 77%, 80%, and 82% of fittings for the
      soft, medium, and loud speech test levels, respectively. Aided maximum power
      output measures were within +/- 5-dB RMS error in 72% of cases. Degree of hearing
      loss, test frequency, and frequency by test level were significant factors in
      deviation from target. The range of aided speech intelligibility index values
      exhibited a strong correlation with the hearing levels of the children tested.
      Conclusion: This study provides evidence that typical hearing aid fittings for
      children can be achieved within +/- 5-dB RMS error of the DSL v5.0 target.
      Greater target deviations were observed at extreme frequencies and as the
      severity of hearing loss increased.

PMID- 28744550
TI  - Working Memory and Speech Recognition in Noise Under Ecologically Relevant
      Listening Conditions: Effects of Visual Cues and Noise Type Among Adults With
      Hearing Loss.
AB  - Purpose: This study evaluated the relationship between working memory (WM) and
      speech recognition in noise with different noise types as well as in the presence
      of visual cues. Method: Seventy-six adults with bilateral, mild to moderately
      severe sensorineural hearing loss (mean age: 69 years) participated. Using a
      cross-sectional design, 2 measures of WM were taken: a reading span measure, and
      Word Auditory Recognition and Recall Measure (Smith, Pichora-Fuller, & Alexander,
      2016). Speech recognition was measured with the Multi-Modal Lexical Sentence Test
      for Adults (Kirk et al., 2012) in steady-state noise and 4-talker babble, with
      and without visual cues. Testing was under unaided conditions. Results: A linear
      mixed model revealed visual cues and pure-tone average as the only significant
      predictors of Multi-Modal Lexical Sentence Test outcomes. Neither WM measure nor
      noise type showed a significant effect. Conclusion: The contribution of WM in
      explaining unaided speech recognition in noise was negligible and not influenced
      by noise type or visual cues. We anticipate that with audibility partially
      restored by hearing aids, the effects of WM will increase. For clinical practice
      to be affected, more significant effect sizes are needed.

PMID- 28744551
TI  - Neural Responses to Multielectrode Stimulation of Healthy and Degenerate Retina.
AB  - Purpose: Simultaneous stimulation of multiple retinal electrodes in normally
      sighted animals shows promise in improving the resolution of retinal prostheses.
      However, the effects of simultaneous stimulation on degenerate retinae remain
      unknown. Therefore, we investigated the characteristics of cortical responses to
      multielectrode stimulation of the degenerate retina. Methods: Four adult cats
      were bilaterally implanted with retinal electrode arrays in the suprachoroidal
      space after unilateral adenosine triphosphate (ATP)-induced retinal photoreceptor
      degeneration. Functional and structural changes were characterized by using
      electroretinogram a-wave amplitude and optical coherence tomography. Multiunit
      activity was recorded from both hemispheres of the visual cortex. Responses to
      single- and multielectrode stimulation of the ATP-injected and fellow control
      eyes were characterized and compared. Results: The retinae of ATP-injected eyes
      displayed structural and functional changes consistent with mid- to late-stage
      photoreceptor degeneration and remodeling. Responses to multielectrode
      stimulation of the ATP-injected eyes exhibited shortened latencies, lower
      saturated spike counts, and higher thresholds, compared to stimulation of the
      fellow control eyes. Electrical receptive field sizes were significantly larger
      in the ATP-injected eye than in the control eye, and positively correlated with
      the extent of degeneration. Conclusions: Significant differences exist between
      cortical responses to stimulation of healthy and degenerate retinae. Our results
      highlight the importance of using a retinal degeneration model when evaluating
      the efficacy of novel stimulation paradigms.

PMID- 28744552
TI  - Macular Vascular Fractal Dimension in the Deep Capillary Layer as an Early
      Indicator of Microvascular Loss for Retinopathy in Type 2 Diabetic Patients.
AB  - Purpose: To determine the ability of fractal dimension to detect early changes in
      the retinal microvascular network imaged by optical coherence tomography
      angiography (OCT-A) in type 2 diabetic patients. Methods: Sixty-seven patients
      with type 2 diabetic mellitus (DM) (48 with no diabetic retinopathy [DR], 19 with
      minimal DR) and 40 control subjects. Macular OCT-A images of the superficial and
      deep retinal capillary layers in a 2.5-mm diameter concentric annular zone
      (excluding the foveal avascular zone) were subdivided into six annular rings and
      four quadrants. A custom automated algorithm was developed to quantify the
      complexity and density of the two retinal capillary layers by fractal analysis.
      Results: Compared to controls, the fractal dimensional parameter (Dbox) of the
      two retinal capillary layers in most regions was significantly lower in diabetic
      patients with minimal DR (P < 0.05). The Dbox of the diabetic patients with no DR
      was also decreased in most regions of the deep retinal capillary layer (P <
      0.05), but not in the superficial retinal capillary layer (P > 0.05). Based on
      the receiver operating characteristic curve analysis, the Dbox values for the
      deep retinal capillary layer had the highest index to discriminate diabetic
      patients with and without minimal DR from controls. Conclusions: Fractal
      dimension based on OCT-A has the potential to quantitatively characterize retinal
      microvascular changes in the early stage of DM. Changes in the fractal dimension
      in the deep retinal capillary layer could be an early indicator of
      microvasculature changes associated with retinopathy in type 2 diabetic patients.

PMID- 28744553
TI  - BRAG2a, a Guanine Nucleotide Exchange Factor for Arf6, Is a Component of the
      Dystrophin-Associated Glycoprotein Complex at the Photoreceptor Terminal.
AB  - Purpose: Mutations in genes encoding the dystrophin-associated glycoprotein
      complex (DGC) can cause muscular dystrophy and disturb synaptic transmission in
      the photoreceptor ribbon synapse. However, the molecular composition and specific
      functions of the photoreceptor DGC remain unknown. Brefeldin A-resistant Arf-GEF
      2 (BRAG2), also known as IQSEC1, is a guanine nucleotide exchange factor for ADP
      ribosylation factor 6 (Arf6), a critical GTPase that regulates endosomal
      trafficking and actin cytoskeleton remodeling. In the present study, we
      characterized the expression of BRAG2a, an alternative splicing isoform of BRAG2,
      in the adult mouse photoreceptor. Methods: Immunofluorescence and immunoelectron
      microscopic analyses of adult mouse retinas were performed using a novel anti
      BRAG2a antibody. Pull-down, immunoprecipitation, and in situ proximity ligation
      assays were performed to examine the interaction between BRAG2a and the DGC in
      vivo. Results: Immunofluorescence demonstrated punctate colocalization of BRAG2a
      with beta-dystroglycan in the outer plexiform layer. Immunoelectron microscopy
      revealed the localization of BRAG2a at the plasma membrane of lateral walls and
      processes of photoreceptor terminals within the synaptic cavity. Pull-down and
      immunoprecipitation assays using retinal lysates demonstrated the protein complex
      formation between BRAG2a with the DGC. In situ proximity ligation assays further
      detected a close spatial relationship between BRAG2a and beta-dystroglycan in the
      outer plexiform layer. Conclusions: The present study provided evidence that
      BRAG2a is a novel component of the photoreceptor DGC, suggesting functional
      involvement of the BRAG2a-Arf6 pathway downstream of the DGC.

PMID- 28744555
TI  - Bacillus catenulatus sp. nov., an alkalitolerant bacterium isolated from a soda
      lake.
AB  - Two novel (18CT and 6C) Gram-stain-positive, rod shaped, motile and endospore
      forming bacterial strains were isolated from Lonar soda lake, India. Based on 16S
      rRNA gene sequence analysis, strains 18CT and 6C were identified as belonging to
      the class Firmibacteria, and were most closely related to Bacillus cohnii KCTC
      3572T (99.3 and 99.9%, respectively), Bacillus zhanjiangensis KCTC 13713T (97.4
      and 98.0%, respectively), Bacillus halmapalus LMG 17950T (97.0 and 97.6%,
      respectively) and other members in the genus Bacillus (<97.0%). However, the DNA
      DNA relatedness between 18CT and 6C and B. cohnii KCTC 3572T (49.6 +/- 0.9 and
      51.6 +/- 0.7, respectively), B. zhanjiangensis KCTC 13713T (42.9 +/- 0.8 and 47.1
      +/- 0.3, respectively) and B. halmapalus LMG 17950T (39.9 +/- 0.8 and 40.8 +/-
      0.3, respectively) indicated that the novel strains were distantly related to
      these strains. Further, the high 16S rRNA gene sequence similarity (100%) and DNA
      DNA relatedness (90 +/- 5%) suggested that strains 18CT and 6C were members of a
      genomospecies. The strains grew optimally at a pH of 7.5 with 2-3% (w/v) NaCl and
      temperature of 37  degrees C. Strains 18CT and 6C were catalase and oxidase
      negative. The cell wall of strain 18CT contained meso-diaminopimelic acid as the
      diagnostic diamino acid, which was in contrast with its nearest neighbour B.
      cohnii KCTC 3572T, which contained ornithine and aspartic acid. Polar lipids
      include diphosphatidylglycerol (DPG), phosphatidylglycerol (PG),
      phosphatidylethanolamine (PE), an unknown phospholipid (PL) and three unknown
      lipids (L1-3). The predominant isoprenoid quinone was MK-7. iso-C15:0 (32.5%) was
      the predominant fatty acid and significant proportions of anteiso-C15:0 (19.5%),
      C16:0 (11.5%), iso-C17:0 (9.5%) and anteiso-C17:0 (6.3%) were also detected. The
      DNA G + C content of strains 18CT and 6C were 39.3 and 39.2 mol%, respectively.
      The results of molecular, biochemical and chemotaxonomic tests showed a clear
      differentiation of strains 18CT and 6C from all other members of the genus
      Bacillus, for which the name Bacillus catenulatus sp. nov. is proposed. The type
      strain is 18CT (=KCTC 33781T = CGMCC 1.15475T).

PMID- 28744554
TI  - Age-Related Alterations in the Retinal Microvasculature, Microcirculation, and
      Microstructure.
AB  - Purpose: To characterize age-related alterations in the retinal microcirculation,
      microvascular network, and microstructure in healthy subjects. Methods: Seventy
      four healthy subjects aged from 18 to 82 years were recruited and divided into
      four age groups (G1 with age <35 years, G2 with age 35 ~ 49 years, G3 with age 50
      ~ 64 years, and G4 with age >=65 years). Custom ultra-high resolution optical
      coherence tomography (UHR-OCT) was used to acquire six intraretinal layers of the
      macula. OCT angiography (OCTA) was used to image the retinal microvascular
      network. The retinal blood flow velocity (BFV) was measured using a Retinal
      Function Imager (RFI). Results: Compared to G1, G2 had significant thinning of
      the retinal nerve fiber layer (RNFL) (P < 0.05), while G3 had thinning of the
      RNFL and ganglion cell and inner plexiform layer (GCIPL) (P < 0.05), in addition
      to thickening of the outer plexiform layer (OPL) and photoreceptor layer (PR) (P
      < 0.05). G4 had loss in retinal vessel density, thinning in RNFL and GCIPL, and
      decrease in venular BFV, in addition to thickening of the OPL and PR (P < 0.05).
      Age was negatively related to retinal vessel densities, the inner retinal layers,
      and venular BFV (P < 0.05). By contrast, age was positively related to OPL and PR
      (P < 0.05). Conclusions: During aging, decreases in retinal vessel density, inner
      retinal layer thickness, and venular BFV were evident and impacted each other as
      observed by simultaneous changes in multiple retinal components.

PMID- 28744557
TI  - Patients' perception and satisfaction with pulsed magnetic stimulation for
      treatment of female stress urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: We evaluated patients' perception and satisfaction
      with nonsurgical pulsed magnetic stimulation (PMS) for treatment of female stress
      urinary incontinence (SUI) in a randomized, double-blind, sham-controlled trial.
      METHODS: Women with SUI (n = 120) were randomized to either active or sham PMS
      for 8 weeks (twice/week). Patients answered seven questions on their perception
      and acceptability, each measured on a 5-point Likert scale. Treatment
      satisfaction was assessed using two parameters: (i) the single-item question
      "Overall, please rate how satisfied you are with the treatment" and (ii) Patient
      Global Impression of Improvement (PGI-I). All adverse events were documented.
      RESULTS: A total of 115 patients completed treatments (active: n = 57, sham: n =
      58). There were no significant differences between groups in all parameters
      regarding perception and acceptability (p > 0.05). In terms of treatment
      satisfaction, a significantly higher proportion of patients in the active group
      (n = 47/57, 82.4%) were either mostly or completely satisfied compared with those
      in the sham group (n = 27/58, 46.6%) ((p = 0.001). Similarly, a statistically
      significantly higher percentage of patients in the active group (n = 39/57,
      68.4%) felt much or very much better compared with patients in the sham group (n
      = 11/58, 19.0%) as measured using the PGI-I (p < 0.001). Three (5.3%) patients in
      the active group and five (8.6%) in the sham group experienced adverse events (p
      = 0.72). Regardless of treatment arms, 109 (94.8%) patients would not consider
      surgical options even if they required further treatment for their condition.
      CONCLUSION: PMS was well accepted, well tolerated, and resulted in a high
      treatment satisfaction among women with SUI.

PMID- 28744559
TI  - Surface tuning laser desorption/ionization mass spectrometry (STLDI-MS) for the
      analysis of small molecules using quantum dots.
AB  - In most applications of quantum dots (QDs) for surface-assisted laser
      desorption/ionization mass spectrometry (SALDI-MS), one side of QDs is supported
      by a solid substrate (stainless - steel plate), whereas the other side is in
      contact with the target analytes. Therefore, the surface capping agent of QDs is
      a key parameter for laser desorption/ionization mass spectrometry (LDI-MS).
      Cadmium telluride quantum dots (CdTe QDs) modified with different capping agents
      are synthesized, characterized, and applied for surface tuning laser
      desorption/ionization mass spectrometry (STLDI-MS). Data shows that CdTe quantum
      dot modified cysteine (cys@CdTe QDs) has an absorption that matches with the
      wavelength of the N2 laser (337 nm). The synergistic effect of large surface area
      and absorption of the laser irradiation of cys@CdTe QDs enhances the LDI-MS
      process for small - molecule analysis, including alpha-, beta-, and gamma
      cyclodextrin, gramicidin D, perylene, pyrene, and triphenylphosphine. Cys@CdTe
      QDs are also applied using Al foils as substrates. Aluminum foil combined with
      cys@CdTe QDs enhances the ionization efficiency and is cheap compared to
      traditional matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) with a stainless - steel plate.

PMID- 28744558
TI  - Fatigability, oxygen uptake kinetics and muscle deoxygenation in incomplete
      spinal cord injury during treadmill walking.
AB  - PURPOSE: The purpose of the present study was to characterize hypothesized
      relationships among fatigability and cardiorespiratory fitness in individuals
      with chronic motor-incomplete SCI (iSCI) during treadmill walking. The
      theoretical framework was that exacerbated fatigability would occur concomitantly
      with diminished cardiorespiratory fitness in people with iSCI. METHODS: Subjects
      with iSCI (n = 8) and an able-bodied reference group (REF) (n = 8) completed a 6
      min walking bout followed by a walking bout of 30-min or until volitional
      exhaustion, both at a self-selected walking speed. Fatigability was assessed
      using both perceived fatigability and performance fatigability measures.
      Pulmonary oxygen uptake kinetics (VO2 on-kinetics) was measured breath-by-breath
      and changes in deoxygenated hemoglobin/myoglobin concentration (?[HHb]) of the
      lateral gastrocnemius was measured by near-infrared spectroscopy. Adjustment of
      VO2 and ?[HHb] on-kinetics were modeled using a mono-exponential equation.
      RESULTS: Perceived fatigability and performance fatigability were 52% and 44%
      greater in the iSCI group compared to the REF group (p = 0.003 and p = 0.004).
      Phase II time constant (taup) of VO2 on-kinetics and ?[HHb] 1/2 time during
      resting arterial occlusion were 55.4% and 16.3% slower in iSCI vs REF (p < 0.01
      and p = 0.047, respectively). CONCLUSIONS: The results of the present study may
      suggest that compromised O2 delivery and/or utilization may have contributed to
      the severity of fatigability in these individuals with iSCI. The understanding of
      the extent to which fatigability and VO2 and Delta[HHb] on-kinetics impacts
      locomotion after iSCI will assist in the future development of targeted
      interventions to enhance function.

PMID- 28744560
TI  - Social impact of analytical chemistry.

PMID- 28744561
TI  - Development of an LC-MS/MS method for the detection of traces of peanut allergens
      in chili pepper.
AB  - The recent detection of nuts (including peanut) in spices across the globe has
      led to enormous recalls of several spices and food products in the last two
      years. The lack of validated detection methods specific for spices makes it
      difficult to assess allergen presence at trace levels. Because of the urgent need
      for confirmation of possible peanut presence in chili peppers, an LC-MS/MS method
      was optimized and developed for this particular food matrix. Although several
      studies optimized LC-MS detection strategies specific for peanuts, the presence
      of complex components in the spices (e.g., phenolic components) makes method
      optimization and validation necessarily. Focus was laid on validation of the
      method with real incurred chili peppers (whereby a known amount of peanut is
      added) at low concentrations, to deal with possible matrix interferences. LC
      MS/MS proves to be a good alternative to the currently most applied methods
      (ELISA and RT-PCR) and can be used as a complementary method of analysis when
      results are unclear. Peanut marker peptides were selected based on their
      abundancy in digested incurred chili peppers. The limit of detection was
      determined to be 24 ppm (mg peanut/kg), a level whereby the risk for potential
      allergic reactions is zero, considering the typical portion size of spices. The
      chili pepper powder under investigation proved to contain low levels of peanuts
      after LC-MS/MS, ELISA, and RT-PCR testing. Graphical abstract Standard curve of
      the detected peanuts in chili pepper samples using the novel LC-MS/MS method.

PMID- 28744562
TI  - Alterations in glutamatergic signaling in the brain of dopamine supersensitivity
      psychosis and non-supersensitivity psychosis model rats.
AB  - BACKGROUND: The long-term administration of antipsychotics is known to induce
      dopamine supersensitivity psychosis (DSP). Although the mechanism of DSP involves
      mainly a compensatory upregulation of dopamine D2 receptors, the precise
      mechanisms underlying DSP are unknown. It is known that glutamatergic signaling
      plays a key role in psychosis. We thus conducted this study to investigate
      whether glutamatergic signaling plays a role in the development of DSP. METHODS:
      Haloperidol (0.75 mg/kg/day for 14 days) or vehicle was administered to rats via
      osmotic mini-pump. Haloperidol-treated rats were divided into groups of DSP rats
      and non-DSP rats based on locomotion data. Tissue levels of glutamate, glutamine,
      glycine, L-serine, D-serine, and GABA and the protein expressions of N-methyl-D
      aspartate receptors (NMDAR), glutamic acid decarboxylase (GAD), and serine
      hydroxymethyltransferase (SHMT) in the rat brain regions were examined. RESULTS:
      In the DSP rats, the ratio of GABA to glutamate was significantly increased. In
      addition, the ratio of L-serine to glycine was increased. The striatal
      expressions of GAD and SHMT2 in the DSP rats were significantly increased. In
      contrast, the striatal expression of NMDAR2B in the non-DSP rats was
      significantly decreased. CONCLUSIONS: The present study suggests that
      glutamatergic signaling is relatively decreased to GABA in DSP rats. Our results
      also showed that excessive doses of haloperidol can induce striatal NMDAR
      hypofunction in non-DSP rats, which could prevent the formation of tardive
      dyskinesia but cause treatment resistance. In view of the need for therapeutic
      strategies for treatment-resistant schizophrenia, further research exploring our
      present findings is necessary.

PMID- 28744564
TI  - Nuance Lost in Translation : Interpretations of J. F. Blumenbach's Anthropology
      in the English Speaking World.
AB  - Johann Friedrich Blumenbach has been called 'The Father of Physical Anthropology'
      because of his pioneering publications describing human racial variation. He
      proposed a racial typology consisting of five 'major varieties/races' of
      humanity. Since the 1990s, Londa Schiebinger and other Anglophone scholars have
      argued that Blumenbach's writings on race show evidence that he was significantly
      influenced by nineteenth-century race supremacist beliefs which held
      Europeans/Caucasians to be the highest ranked and most beautiful race. However,
      these modern authors relied largely on Thomas Bendyshe's 1865 English
      translations of Blumenbach's Latin and German texts. As documented herein,
      Bendyshe's publication includes numerous translation errors which form a pattern
      indicating that he employed two translators. The first translator was consistent
      with five earlier English translations. The second translator was not consistent
      with the earlier translators. This second translator also used English terms that
      denigrated extra-Europeans while adulating Europeans. Furthermore, Bendyshe's1865
      translation regularly used the term 'beauty' to translate different Latin words
      that Blumenbach used to express his nuanced view of aesthetics and structural
      symmetry. Given the inconsistency and errors in Bendyshe's 1865 translations,
      they should not be unquestionably accepted as an accurate reflection of
      Blumenbach's views.

PMID- 28744563
TI  - MAM-E17 rat model impairments on a novel continuous performance task: effects of
      potential cognitive enhancing drugs.
AB  - RATIONALE: Impairments in attention and inhibitory control are endophenotypic
      markers of neuropsychiatric disorders such as schizophrenia and represent key
      targets for therapeutic management. Robust preclinical models and assays
      sensitive to clinically relevant treatments are crucial for improving cognitive
      enhancement strategies. OBJECTIVES: We assessed a rodent model with neural and
      behavioral features relevant to schizophrenia (gestational day 17
      methylazoxymethanol acetate treatment (MAM-E17)) on a novel test of attention and
      executive function, and examined the impact of putative nootropic drugs. METHODS:
      MAM-E17 and sham control rats were trained on a novel touchscreen-based rodent
      continuous performance test (rCPT) designed to closely mimic the human CPT
      paradigm. Performance following acute, systemic treatment with an array of
      pharmacological compounds was investigated. RESULTS: Two cohorts of MAM-E17 rats
      were impaired on rCPT performance including deficits in sensitivity (d') and
      increased false alarm rates (FARs). Sulpiride (0-30 mg/kg) dose-dependently
      reduced elevated FAR in MAM-E17 rats whereas low-dose modafinil (8 mg/kg) only
      improved d' in sham controls. ABT-594 (5.9-19.4 MUg/kg) and modafinil (64 mg/kg)
      showed expected stimulant-like effects, while LSN2463359 (5 mg/kg), RO493858 (10
      mg/kg), atomoxetine (0.3-1 mg/kg), and sulpiride (30 mg/kg) showed expected
      suppressant effects on performance across all animals. Donepezil (0.1-1 mg/kg)
      showed near-significant enhancements in d', and EVP-6124 (0.3-3 mg/kg) exerted no
      effects in the rCPT paradigm. CONCLUSION: The MAM-E17 model exhibits robust and
      replicable impairments in rCPT performance that resemble attention and inhibitory
      control deficits seen in schizophrenia. Pharmacological profiles were highly
      consistent with known drug effects on cognition in preclinical and clinical
      studies. The rCPT is a sensitive and reliable tool with high translational
      potential for understanding the etiology and treatment of disorders affecting
      attention and executive dysfunction.

PMID- 28744565
TI  - The general relationship between internalizing psychopathology and chronic
      physical health conditions: a population-based study.
AB  - Studies have consistently demonstrated a reciprocal relationship between
      internalizing disorders and several chronic physical health conditions. Yet, much
      of the extant literature fails to take into account the role of comorbidity among
      internalizing disorders when examining the relationship with poor physical
      health. The current study applied latent variable modelling to investigate the
      shared and specific relationships between internalizing (fear and distress
      factors) and a range of physical health conditions. Data comprised 8841
      respondents aged 16-85 years who took part in the 2007 Australian National Survey
      of Mental Health and Wellbeing. Multiple indicator, multiple causes models were
      used to parse the shared and specific relationships between internalizing
      disorders and variables associated with poor physical health. The study found
      that several physical conditions were significantly related to mean levels of
      fear and distress. The results were broadly similar but minor differences emerged
      depending on whether lifetime or past 12 months indicators of mental disorders
      and physical conditions were utilized in the model. Finally, the results
      demonstrated that the association between individual mental disorders and
      physical health conditions are better accounted for by indirect relationships
      with broad transdiagnostic dimensions rather than including additional disorder
      specific relationships. The results indicate that researchers should focus on
      common mechanisms across multiple internalizing disorders and poor physical
      health when developing prevention and treatment initiatives.

PMID- 28744566
TI  - Association between renal function and cardiovascular and all-cause mortality in
      the community-based elderly population: results from the Specific Health Check
      and Guidance Program in Japan.
AB  - BACKGROUND: Chronic kidney disease is a significant risk factor for end-stage
      kidney disease, cardiovascular events, and premature death. However, the
      prognostic value of low estimated glomerular filtration rate (eGFR) in the
      elderly is debatable. METHODS: We determined eGFR using the Japanese equation in
      132,160 elderly subjects (65-75 years) who attended the special health checkup
      (Tokutei-Kenshin) in 2008 and investigated the association between baseline eGFR
      and 5-year all-cause and cardiovascular mortality. RESULTS: The median (SD) eGFR
      was 70.5 +/- 15.3 mL/min/1.73 m2. During follow-up, we noted 2045 all-cause
      deaths including 408 from cardiovascular events. A J-shaped curve was obtained
      when all-cause and cardiovascular mortality rates were compared with decreases in
      eGFR, with the highest mortality observed for eGFR <45 mL/min/1.73 m2. These
      trends were statistically significant in the Kaplan-Meier analysis (P < 0.001).
      In the Cox proportional hazard analysis, after adjusting for possible
      confounders, those with eGFR <45 mL/min/1.73 m2, but not eGFR 45-59 mL/min/1.73
      m2 showed a higher all-cause and cardiovascular mortality than those with eGFR
      >90 mL/min/1.73 m2 [hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.06
      1.91 for all-cause mortality, HR 2.28, 95% CI 1.28-4.03 for cardiovascular
      mortality]. Sex-based subgroup analyses showed similar results for both men and
      women. CONCLUSIONS: We conclude that eGFR <45 mL/min/1.73 m2 is an independent
      risk factor for all-cause and cardiovascular mortality in the elderly population.

PMID- 28744567
TI  - Response to the reply by C. J. Portier and P. Clausing, concerning our review
      "Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the
      European Union assessment and its differences with IARC".

PMID- 28744568
TI  - Enhanced hydrolysis of cellulose hydrogels by morphological modification.
AB  - Cellulose is one of the most abundant bio-renewable materials on earth, yet the
      potential of cellulosic bio-fuels is not fully exploited, primarily due to the
      high costs of conversion. Hydrogel particles of regenerated cellulose constitute
      a useful substrate for enzymatic hydrolysis, due to their porous and amorphous
      structure. This article describes the influence of several structural aspects of
      the cellulose hydrogel on its hydrolysis. The hydrogel density was shown to be
      directly proportional to the cellulose concentration in the initial solution,
      thus affecting its hydrolysis rate. Using high-resolution scanning electron
      microscopy, we show that the hydrogel particles in aqueous suspension exhibit a
      dense external surface layer and a more porous internal network. Elimination of
      the external surface layer accelerated the hydrolysis rate by up to sixfold and
      rendered the process nearly independent of cellulose concentration. These
      findings may be of practical relevance to saccharification processing costs, by
      reducing required solvent quantities and enzyme load.

PMID- 28744569
TI  - UV-C Adaptation of Shigella: Morphological, Outer Membrane Proteins, Secreted
      Proteins, and Lipopolysaccharides Effects.
AB  - Water UV disinfection remains extremely important, particularly in developing
      countries where drinking and reclaimed crop irrigation water may spread
      devastating infectious diseases. Enteric bacterial pathogens, among which
      Shigella, are possible contaminants of drinking and bathing water and foods. To
      study the effect of UV light on Shigella, four strains were exposed to different
      doses in a laboratory-made irradiation device, given that the ultraviolet
      radiation degree of inactivation is directly related to the UV dose applied to
      water. Our results showed that the UV-C rays are effective against all the tested
      Shigella strains. However, UV-C doses appeared as determinant factors for
      Shigella eradication. On the other hand, Shigella-survived strains changed their
      outer membrane protein profiles, secreted proteins, and lipopolysaccharides.
      Also, as shown by electron microscopy transmission, morphological alterations
      were manifested by an internal cytoplasm disorganized and membrane envelope
      breaks. Taken together, the focus of interest of our study is to know the
      adaptive mechanism of UV-C resistance of Shigella strains.

PMID- 28744571
TI  - What determines the importance of a species for ecosystem processes? Insights
      from tropical ant assemblages.
AB  - Biodiversity is known to increase ecosystem functioning. However, species vary in
      their contributions to ecosystem processes. Here, we investigated seven ecosystem
      functions based on the consumption of different resources in tropical ant
      communities. We analysed how different species influence site-level resource
      consumption, and determined how each species influenced performance and stability
      of these functions. Based on simulated extinctions, we identified 'key species'
      with significant functional contributions. We then investigated which traits,
      such as biomass, abundance, and specialisation, characterized them, and compared
      trait distributions across four sites to analyse differences in functional
      redundancy. Only few species significantly influenced ecosystem functions. Common
      generalist species tended to be the most important drivers of many ecosystem
      functions, though several specialist species also proved to be important in this
      study. Moreover, species-specific ecological impacts varied across sites. In
      addition, we found that functional redundancy varied across sites, and was
      highest in sites where the most common species did not simultaneously have the
      greatest functional impacts. Furthermore, redundancy was enhanced in sites where
      species were less specialised and had more even incidence distributions. Our
      study demonstrates that the ecological importance of a species depends on its
      functional traits, but also on the community context. It cannot be assessed
      without investigating its species-specific performance across multiple functions.
      Hence, to assess functional redundancy in a habitat and the potential for
      compensation of species loss, researchers need to study species-specific traits
      that concern functional performance as well as population dynamics and tolerance
      to environmental conditions.

PMID- 28744570
TI  - Strategies for Biofilm Inhibition and Virulence Attenuation of Foodborne Pathogen
      Escherichia coli O157:H7.
AB  - Enterohemorrhagic Escherichia coli (E. coli) O157:H7, a gram-negative bacteria
      identified as a foodborne pathogen causing severe disease is of great concern
      worldwide. The pathogenicity of E. coli O157:H7 is due to the presence of some
      virulence factors and its ability to form biofilm which resist antimicrobial
      compounds, withstand harsh environmental condition and protects from the host
      immune responses. Formation of biofilm is a multistep process such as adhesion,
      cellular aggregation and productions of extracellular matrix in which colonies
      are embedded. There are high numbers of research in the discovery of natural and
      synthetic compounds which can attenuate the E. coli O157:H7 biofilm formation as
      well as suppress virulence-related genes. The present review article focuses on
      the steps involved in E. coli O157:H7 biofilm formation, factors associated with
      virulence and attenuation.

PMID- 28744572
TI  - Does the presence of coronary artery disease affect the outcome of aortic valve
      replacement?
AB  - The purpose of this study is to compare the late outcome of aortic valve
      replacement with or without preoperative coronary artery disease, and with or
      without coronary artery bypass. Between 2014 and 2015, 291 patients underwent
      aortic valve replacement. Average follow-up term was 2.5 +/- 2.2 years. The
      retrospective comparative study was performed between the patients with (n = 115)
      or without (n = 176) preoperative coronary artery disease (Study 1) and with (n =
      93) or without (n = 198) coronary artery bypass grafting (Study 2). Study 1: male
      patients were more, and diabetes was more in the patients with coronary artery
      disease. Long-term survival rate was significantly low in the patients with
      coronary artery disease (p = 0.0002 by log rank test). Freedom from repeat
      coronary revascularization rate was lower in the patients with coronary artery
      disease (p = 0.02 by log rank test). Study 2: operation time (419 +/- 130 vs 290
      +/- 101; p = 0.0001) was longer in the patients with coronary artery bypass
      grafting. Improvement of ejection fraction at follow-up was more in the patients
      with coronary artery bypass(114 +/- 43 vs 104 +/- 26%; p = 0.03). Long-term
      survival rate and freedom from major adverse cardiac event rater were not
      different with or without coronary artery bypass grafting (p = 0.26 and p = 0.59,
      respectively, by log rank test). Although prevalence of coronary artery disease
      inversely affected the long-term outcome of the aortic valve replacement,
      simultaneous coronary artery bypass did not. Aggressive simultaneous coronary
      revascularization would be important to improve the long-term outcome of aortic
      valve replacement.

PMID- 28744574
TI  - Response to Letter.

PMID- 28744573
TI  - Dietary patterns and changes in frailty status: the Rotterdam study.
AB  - PURPOSE: To determine the associations between a priori and a posteriori derived
      dietary patterns and a general state of health, measured as the accumulation of
      deficits in a frailty index. METHODS: Cross-sectional and longitudinal analysis
      embedded in the population-based Rotterdam Study (n = 2632) aged 45 years. Diet
      was assessed at baseline (year 2006) using food frequency questionnaires. Dietary
      patterns were defined a priori using an existing index reflecting adherence to
      national dietary guidelines and a posteriori using principal component analysis.
      A frailty index was composed of 38 health deficits and measured at baseline and
      follow-up (4 years later). Linear regression analyses were performed using
      adherence to each of the dietary patterns as exposure and the frailty index as
      outcome (all in Z-scores). RESULTS: Adherence to the national dietary guidelines
      was associated with lower frailty at baseline (beta -0.05, 95% CI -0.08, -0.02).
      Additionally, high adherence was associated with lower frailty scores over time
      (beta -0.08, 95% CI -0.12, -0.04). The PCA revealed three dietary patterns that
      we named a "Traditional" pattern, high in legumes, eggs and savory snacks; a
      "Carnivore" pattern, high in meat and poultry; and a "Health Conscious" pattern,
      high in whole grain products, vegetables and fruit. In the cross-sectional
      analyses adherence to these patterns was not associated with frailty. However,
      adherence to the "Traditional" pattern was associated with less frailty over time
      (beta -0.09, 95% CI -0.14, -0.05). CONCLUSION: No associations were found for
      adherence to a "healthy" pattern or "Carnivore" pattern. However, Even in a
      population that is relatively young and healthy, adherence to dietary guidelines
      or adherence to the Traditional pattern could help to prevent, delay or reverse
      frailty levels.

PMID- 28744575
TI  - All-treatment array of hepatocellular carcinoma from initial diagnosis to death:
      observation of cumulative treatments.
AB  - PURPOSE: In clinical practice, most patients with hepatocellular carcinoma
      require subsequent treatments for remaining, progressing, or recurring tumors. We
      investigated all-treatment array and outcomes in an HCC cohort from initial
      diagnosis to death. METHODS: We enrolled 1687 consecutive patients with HCC who
      underwent initial diagnosis and treatment at the National Cancer Center, Korea,
      from January 2004 to December 2009. RESULTS: In total, 1357 patients (80.4%)
      showed RPRTs during median 20.4-month follow-up. Initial transplantation resulted
      in the least rate (32.3%) of RPRTs. Median treatment frequency was 3.0 times
      (range 1-20) and 382 patients (27.3%) received treatments >=6 times. The median
      treatment frequency was different based on four factors (p < 0.05): age, tumor
      stage, tumor type and initial treatment modality. Patients with Barcelona Clinic
      Liver Cancer stage 0 received less frequent treatments. As the stage progressed
      from 0 to B, the median treatment frequency increased. Radiofrequency ablation as
      initial treatment was associated with the longest median treatment interval at
      19.0 weeks, followed by resection at 14.1 weeks. The median treatment interval
      was significantly shorter as the stage progressed (p < 0.01). TACE was most
      frequently performed for RPRTs; the median number of subsequent TACE was 3 (range
      1-19). Subsequent treatment array was very heterogeneous, and no certain pattern
      was found. CONCLUSIONS: Our findings suggest that the survival outcome of
      patients with HCC is based on the results of cumulative multiple treatments
      rather than an initial treatment. It is time to consider prospective studies
      evaluating sequential treatment array of HCC.

PMID- 28744576
TI  - Cytogenetics with flow cytometry in lymph node/extranodal tissue biopsies is
      sensitive to assist the early diagnosis of suspected lymphomas.
AB  - Few studies have examined the value of cytogenetic studies with flow cytometry
      (FC) in lymph node/extranodal tissue biopsies with suspected lymphoma. To
      evaluate this, G-banded karyotyping and/or fluorescence in situ hybridization
      (FISH) with FC immunophenotyping were performed on 185 lymph node or extranodal
      tissue biopsy specimens with suspected lymphoma. Complete cytogenetic analysis of
      lymph node/extranodal tissue was successful in 174 cases (94.1%) and 57.5%
      demonstrated chromosomal abnormalities. In 116 malignant lymphoma cases, 83.8%
      showed abnormalities. In 74 B cell lymphomas (B-NHL), abnormalities were more
      frequent in lymph node/extranodal tissues than in bone marrow by conventional
      cytogenetics (CC, 97.2 vs 26.1%), FISH (70.6 vs 17.6%), and FC (98.6 vs 28.4%).
      Three B-NHL diagnoses were confirmed by re-biopsy of lymph nodes due to the
      presence of abnormalities in the first biopsy, but no evidence of malignancy in
      pathological, FC, or IgH/TCR gene rearrangement analyses. In 29 T cell lymphomas
      (T-NHL), abnormalities were more frequent in lymph nodes than in bone marrow by
      CC (67.9 vs 21.4%) and FC (75.9 vs 27.6%) analyses. As expected, in 13 Hodgkin
      lymphoma cases, abnormalities were more frequent in lymph nodes than bone marrow
      by CC (41.7 vs 16.7%) and FC (30.8 vs 7.7%) analyses. In 56 reactive lymphoid
      hyperplasias (RLH), 7.1% had conventional clonal cytogenetic abnormalities. Two
      of these patients died of disease progression and two had their pathological
      diagnosis revised after the second review. These findings indicate that
      cytogenetic analysis combined with FC in lymph node/extranodal tissue biopsies
      can provide critical information in the auxiliary diagnosis of lymphoma.

PMID- 28744577
TI  - Quantitative metabolomics of a xylose-utilizing Saccharomyces cerevisiae strain
      expressing the Bacteroides thetaiotaomicron xylose isomerase on glucose and
      xylose.
AB  - The yeast Saccharomyces cerevisiae cannot utilize xylose, but the introduction of
      a xylose isomerase that functions well in yeast will help overcome the
      limitations of the fungal oxido-reductive pathway. In this study, a diploid S.
      cerevisiae S288c[2n YMX12] strain was constructed expressing the Bacteroides
      thetaiotaomicron xylA (XI) and the Scheffersomyces stipitis xyl3 (XK) and the
      changes in the metabolite pools monitored over time. Cultivation on xylose
      generally resulted in gradual changes in metabolite pool size over time, whereas
      more dramatic fluctuations were observed with cultivation on glucose due to the
      diauxic growth pattern. The low G6P and F1,6P levels observed with cultivation on
      xylose resulted in the incomplete activation of the Crabtree effect, whereas the
      high PEP levels is indicative of carbon starvation. The high UDP-D-glucose levels
      with cultivation on xylose indicated that the carbon was channeled toward biomass
      production. The adenylate and guanylate energy charges were tightly regulated by
      the cultures, while the catabolic and anabolic reduction charges fluctuated
      between metabolic states. This study helped elucidate the metabolite distribution
      that takes place under Crabtree-positive and Crabtree-negative conditions when
      cultivating S. cerevisiae on glucose and xylose, respectively.

PMID- 28744578
TI  - Synthesis of citramalic acid from glycerol by metabolically engineered
      Escherichia coli.
AB  - Citramalic acid (citramalate) serves as a five-carbon precursor for the chemical
      synthesis of methacrylic acid. We compared citramalate and acetate accumulation
      from glycerol using Escherichia coli strains expressing a modified citramalate
      synthase gene cimA from Methanococcus jannaschii. These studies revealed that
      gltA coding citrate synthase, leuC coding 3-isopropylmalate dehydratase, and
      acetate pathway genes play important roles in elevating citramalate and
      minimizing acetate formation. Controlled 1.0 L batch experiments confirmed that
      deletions in all three acetate-production genes (poxB, ackA, and pta) were
      necessary to reduce acetate formation to less than 1 g/L during citramalate
      production from 30 g/L glycerol. Fed-batch processes using MEC568/pZE12-cimA
      (gltA leuC ackA-pta poxB) generated over 31 g/L citramalate and less than 2 g/L
      acetate from either purified or crude glycerol at yields exceeding 0.50 g
      citramalate/g glycerol in 132 h. These results hold promise for the viable
      formation of citramalate from unrefined glycerol.

PMID- 28744579
TI  - Triple serine loop region regulates the aspartate racemase activity of the
      serine/aspartate racemase family.
AB  - Recently, we cloned and characterized eleven serine and aspartate racemases (SerR
      and AspR, respectively) from animals. These SerRs and AspRs are not separated by
      their racemase functions and form a serine/aspartate racemase family cluster
      based on phylogenetic analysis. Moreover, we have proposed that the AspR-specific
      triple serine loop region at amino acid positions 150-152 may be responsible for
      the large AspR activity. In the present study, to test this hypothesis, we
      prepared and characterized fourteen mutants in this region of animal SerRs and
      AspRs. The large AspR activity in Acropora and Crassostrea AspR was reduced to
      <0.04% of wild-type after substitution of the triple serine loop region.
      Conversely, introducing the triple serine loop region into Acropora, Crassostrea,
      and Penaeus SerR drastically increased the AspR activity. Those mutants showed
      similar or higher substrate affinity for aspartate than serine and showed 11-683
      fold higher k cat and 28-351-fold higher k cat/K m values for aspartate than
      serine racemization. Furthermore, we introduced serine residues in all
      combinations at position 150-152 in mouse SerR. These mutants revealed that a
      change in the enzyme function from SerR to AspR can be caused by introduction of
      Ser151 and Ser152, and addition of the third serine residue at position 150
      further enhances the enzyme specificity for aspartate due to a decrease in the
      serine racemase and serine dehydratase activity. Here, we provide convincing
      evidence that the AspR gene has evolved from the SerR gene by acquisition of the
      triple serine loop region.

PMID- 28744580
TI  - Stabilization of Angiotensin-(1-7) by key substitution with a cyclic non-natural
      amino acid.
AB  - Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin
      aldosterone system, is a promising candidate as a treatment for cancer that
      reflects its anti-proliferative and anti-angiogenic properties. However, the
      peptide's therapeutic potential is limited by the short half-life and low
      bioavailability resulting from rapid enzymatic metabolism by peptidases including
      angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report
      the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide
      synthesis which incorporates the cyclic non-natural delta-amino acid ACCA. The
      analogues containing the ACCA substitution at the site of ACE cleavage exhibit
      complete resistance to human ACE, while substitution at the DDP 3 cleavage site
      provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain
      the anti-proliferative properties of Ang-(1-7) against the 4T1 and HT-1080 cancer
      cell lines. These results suggest that ACCA-substituted Ang-(1-7) analogues which
      show resistance against proteolytic degradation by peptidases known to hydrolyze
      the native heptapeptide may be novel therapeutics in the treatment of cancer.

PMID- 28744581
TI  - Redefining the Practice of Peer Review Through Intelligent Automation-Part 3:
      Automated Report Analysis and Data Reconciliation.
AB  - One method for addressing existing peer review limitations is the assignment of
      peer review cases on a completely blinded basis, in which the peer reviewer would
      create an independent report which can then be cross-referenced with the primary
      reader report of record. By leveraging existing computerized data mining
      techniques, one could in theory automate and objectify the process of report data
      extraction, classification, and analysis, while reducing time and resource
      requirements intrinsic to manual peer review report analysis. Once inter-report
      analysis has been performed, resulting inter-report discrepancies can be
      presented to the radiologist of record for review, along with the option to
      directly communicate with the peer reviewer through an electronic data
      reconciliation tool aimed at collaboratively resolving inter-report discrepancies
      and improving report accuracy. All associated report and reconciled data could in
      turn be recorded in a referenceable peer review database, which provides
      opportunity for context and user-specific education and decision support.

PMID- 28744582
TI  - Redefining the Practice of Peer Review Through Intelligent Automation Part 1:
      Creation of a Standardized Methodology and Referenceable Database.
AB  - Conventional peer review practice is compromised by a number of well-documented
      biases, which in turn limit standard of care analysis, which is fundamental to
      determination of medical malpractice. In addition to these intrinsic biases,
      other existing deficiencies exist in current peer review including the lack of
      standardization, objectivity, retrospective practice, and automation. An
      alternative model to address these deficiencies would be one which is completely
      blinded to the peer reviewer, requires independent reporting from both parties,
      utilizes automated data mining techniques for neutral and objective report
      analysis, and provides data reconciliation for resolution of finding-specific
      report differences. If properly implemented, this peer review model could result
      in creation of a standardized referenceable peer review database which could
      further assist in customizable education, technology refinement, and
      implementation of real-time context and user-specific decision support.

PMID- 28744583
TI  - DICOM Standard Conformance in Veterinary Medicine in Germany: a Survey of Imaging
      Studies in Referral Cases.
AB  - In 2016, the recommendations of the DICOM Standards Committee for the use of
      veterinary identification DICOM tags had its 10th anniversary. The goal of our
      study was to survey veterinary DICOM standard conformance in Germany regarding
      the specific identification tags veterinarians should use in veterinary
      diagnostic imaging. We hypothesized that most veterinarians in Germany do not
      follow the guidelines of the DICOM Standards Committee. We analyzed the metadata
      of 488 imaging studies of referral cases from 115 different veterinary
      institutions in Germany by computer-aided DICOM header readout. We found that 25
      (5.1%) of the imaging studies fully complied with the "veterinary DICOM standard"
      in this survey. The results confirmed our hypothesis that the recommendations of
      the DICOM Standards Committee for the consistent and advantageous use of
      veterinary identification tags have found minimal acceptance amongst German
      veterinarians. DICOM does not only enable connectivity between machines, DICOM
      also improves communication between veterinarians by sharing correct and valuable
      metadata for better patient care. Therefore, we recommend that lecturers,
      universities, societies, authorities, vendors, and other stakeholders should
      increase their effort to improve the spread of the veterinary DICOM standard in
      the veterinary world.

PMID- 28744585
TI  - Metabolite Clearance During Wakefulness and Sleep.
AB  - Mechanisms for elimination of metabolites from ISF include metabolism, blood
      brain barrier transport and non-selective, perivascular efflux, this last being
      assessed by measuring the clearance of markers like inulin. Clearance describes
      elimination. Clearance of a metabolite generated within the brain is determined
      as its elimination rate divided by its concentration in interstitial fluid (ISF).
      However, the more frequently measured parameter is the rate constant for
      elimination determined as elimination rate divided by amount present, which thus
      depends on both the elimination processes and the distribution of the metabolite
      in the brain. The relative importance of the various elimination mechanisms
      depends on the particular metabolite. Little is known about the effects of sleep
      on clearance via metabolism or blood-brain barrier transport, but studies with
      inulin in mice comparing perivascular effluxes during sleep and wakefulness
      reveal a 4.2-fold increase in clearance. Amongst the important brain metabolites
      considered, CO2 is eliminated so rapidly across the blood-brain barrier that
      clearance is blood flow limited and elimination quickly balances production.
      Glutamate is removed from ISF primarily by uptake into astrocytes and conversion
      to glutamine, but also by transport across the blood-brain barrier. Both lactate
      and amyloid-beta are eliminated by metabolism, blood-brain barrier transport and
      perivascular efflux and both show decreased production, decreased ISF
      concentration and increased perivascular clearance during sleep. Taken altogether
      available data indicate that sleep increases perivascular and non-perivascular
      clearances for amyloid-beta which reduces its concentration and may have long
      term consequences for the formation of plaques and cerebral arterial deposits.

PMID- 28744584
TI  - Predictors for unintentional medication reconciliation discrepancies in
      preadmission medication: a systematic review.
AB  - PURPOSE: Discrepancies in preadmission medication (PAM) are common and
      potentially harmful. Medication reconciliation is able to reduce the discrepancy
      rate, yet implementation is challenging. In order for reconciliation efforts to
      be more cost-effective, patients at high risk for reconciliation errors should be
      identified. The purpose of this systematic review is to identify predictors for
      unintentional discrepancies in PAM. METHODS: Medline and Embase were searched
      systematically until June 2017. Only studies concerning adult subjects were
      retained. Quantitative studies were included if predictors for unintentional
      discrepancies in the PAM had been determined on hospital admission. Variables
      were divided into patient-, medication-, and setting-related predictors based on
      a thematic analysis. Studies on identification of predictors for discrepancies
      and potentially harmful discrepancies were handled separately. RESULTS: Thirty
      five studies were eligible, of which 5 studies focused on potentially harmful
      discrepancies. The following 16 significant variables were identified using
      multivariable prediction models: number of preadmission drugs, patient's age,
      availability of a drug list, patients' understanding of medication, usage of
      different outpatient pharmacies, number of high-risk drugs, discipline for which
      the patient is admitted, admitting physician's experience, number and type of
      consulted sources, patient's gender, type of care before admission, number of
      outpatient visits during the past year, class of medication, number of
      reimbursements, use of an electronic prescription system, and type of admission
      (elective vs emergency). The number of preadmission drugs was identified as a
      predictor in 20 studies. Potentially harmful discrepancies were ascertained in 5
      studies with age found to have a predictive value in all 5 studies. CONCLUSION:
      Multiple suitable predictors for PAM-related discrepancies were identified of
      which higher age and polypharmacy were reported most frequently.

PMID- 28744586
TI  - Sigma1 Pharmacology in the Context of Cancer.
AB  - Sigma1 (also known as sigma-1 receptor, Sig1R, sigma1 receptor) is a unique
      pharmacologically regulated integral membrane chaperone or scaffolding protein.
      The majority of publications on the subject have focused on the neuropharmacology
      of Sigma1. However, a number of publications have also suggested a role for
      Sigma1 in cancer. Although there is currently no clinically used anti-cancer drug
      that targets Sigma1, a growing body of evidence supports the potential of Sigma1
      ligands as therapeutic agents to treat cancer. In preclinical models, compounds
      with affinity for Sigma1 have been reported to inhibit cancer cell proliferation
      and survival, cell adhesion and migration, tumor growth, to alleviate cancer
      associated pain, and to have immunomodulatory properties. This review will
      highlight that although the literature supports a role for Sigma1 in cancer,
      several fundamental questions regarding drug mechanism of action and the
      physiological relevance of aberrant SIGMAR1 transcript and Sigma1 protein
      expression in certain cancers remain unanswered or only partially answered.
      However, emerging lines of evidence suggest that Sigma1 is a component of the
      cancer cell support machinery, that it facilitates protein interaction networks,
      that it allosterically modulates the activity of its associated proteins, and
      that Sigma1 is a selectively multifunctional drug target.

PMID- 28744587
TI  - Analysis of root surface properties by fluorescence/Raman intensity ratio.
AB  - The aim of this study is to evaluate the existence of residual calculus on root
      surfaces by determining the fluorescence/Raman intensity ratio. Thirty-two
      extracted human teeth, partially covered with calculus on the root surface, were
      evaluated by using a portable Raman spectrophotometer, and a 785-nm, 100-mW laser
      was applied for fluorescence/Raman excitation. The collected spectra were
      normalized to the hydroxyapatite Raman band intensity at 960 cm-1. Raman spectra
      were recorded from the same point after changing the focal distance of the laser
      and the target radiating angle. In seven teeth, the condition of calculus,
      cementum, and dentin were evaluated. In 25 teeth, we determined the
      fluorescence/Raman intensity ratio following three strokes of debridement. Raman
      spectra collected from the dentin, cementum, and calculus were different. After
      normalization, spectra values were constant. The fluorescence/Raman intensity
      ratio of calculus region showed significant differences compared to the cementum
      and dentin (p < 0.05). The fluorescence/Raman intensity ratio decreased with
      calculus debridement. For this analysis, the delta value was defined as the
      difference between the values before and after three strokes, with the final 2
      delta values close to zero, indicating a gradual asymptotic curve and the change
      in intensity ratio approximating that of individual constants. Fluorescence/Raman
      intensity ratio was effectively used to cancel the angle- and distance-dependent
      fluctuations of fluorescence collection efficiency during measurement. Changes in
      the fluorescence/Raman intensity ratio near zero suggested that cementum or
      dentin was exposed, and calculus removed.

PMID- 28744588
TI  - MAGEA4 expression in bone and soft tissue tumors: its utility as a target for
      immunotherapy and diagnostic marker combined with NY-ESO-1.
AB  - Cancer-testis (CT) antigens have promise as targets for immunotherapy, because of
      their restricted expression in tumor or testis tissue. MAGEA4 is both a MAGE
      family member and a CT antigen, and has attracted attention as a potential
      immunotherapeutic target. We investigated MAGEA4 expression by
      immunohistochemistry in bone and soft tissue tumor specimens that consisted of 35
      malignant or intermediate and 24 benign histological subtypes, in order to
      evaluate its possible utility as an immunotherapy target and its potential use as
      a diagnostic marker when combined with another CT antigen, NY-ESO-1. Among these
      tumors, MAGEA4 was detected in 82.2% of synovial sarcomas, 67.7% of myxoid
      liposarcomas, 43.8% of osteosarcomas, 41.4% of angiosarcomas, 24.6% of malignant
      peripheral nerve sheath tumors (MPNSTs), and 21.4% of chondrosarcomas. NY-ESO-1
      expression was found in 88.2% of myxoid liposarcomas, 61.1% of synovial sarcomas,
      31.3% of osteosarcomas, 21.4% of pleomorphic liposarcomas, 16.7% of desmoplastic
      small round cell tumors, and 14.3% of chondrosarcomas. Benign tumors and non
      tumorous tissue, except for testis tissue, did not express MAGEA4 or NY-ESO-1.
      Combined use of MAGEA4 and NY-ESO-1 increased the sensitivity, specificity,
      positive predictive values, and negative predictive values for distinguishing
      synovial sarcoma from spindle cell tumors and other mimicking tumors, compared to
      individual use of MAGEA4 or NY-ESO-1. Our results support the immunotherapy
      targeting MAGEA4 or NY-ESO-1 can be an ancillary therapy in the above-mentioned
      tumors, and the potential utility of MAGEA4 as an ancillary diagnostic marker for
      synovial sarcoma combined with NY-ESO-1.

PMID- 28744589
TI  - Circulating fibroblast growth factor 21 in patients with liver cirrhosis.
AB  - Fibroblast growth factor 21 (FGF21) is an adipokine and hepatokine, and its
      hepatic expression is induced in the injured liver. Adiponectin, whose systemic
      levels are positively correlated with measures of hepatic injury in patients with
      liver cirrhosis, is a downstream effector of FGF21. The aim of the present study
      was to identify possible associations of serum FGF21 with measures of liver
      function in patients with liver cirrhosis. FGF21 was determined by ELISA in serum
      of 42 patients. FGF21 was not linked to disease severity assessed by the Child
      Pugh and MELD score. Levels were not changed in those patients with varices
      and/or ascites. Systemic FGF21 did not correlate with markers of liver and kidney
      function, inflammatory proteins or adipokines like adiponectin. Levels in hepatic
      and portal vein of 37 patients were also measured, but there was no transhepatic
      FGF21 gradient. Three months after insertion of a transjugular intrahepatic shunt
      hepatic venous pressure gradient was markedly improved, while FGF21 in serum of
      these 13 patients was not changed. The present study shows that hepatic release
      and systemic FGF21 are not linked to measures of liver function in patients with
      liver cirrhosis.

PMID- 28744590
TI  - CSF tapping also improves mental imagery of gait in normal pressure
      hydrocephalus.
AB  - This study aims to compare the changes of Timed Up and Go (TUG) and its imagined
      version (iTUG) after CSF tapping between patients with idiopathic normal pressure
      hydrocephalus (iNPH) and its mimics. TUG and iTUG were performed before and 24 h
      after CSF tapping in 117 patients (75.8 +/- 6.9 years; 35% female) with suspicion
      of iNPH (68 iNPH and 49 mimics). Mental imagery of locomotion was modified after
      CSF tapping in iNPH patients, but not in the mimics.

PMID- 28744591
TI  - The virulence factor PA protein of highly pathogenic H5N1 avian influenza virus
      inhibits NF-kappaB transcription in vitro.
AB  - Nuclear factor kappa B (NF-kappaB) plays a crucial role in inflammation and
      immune responses. Our previous studies have demonstrated that the innate immune
      response affect H5N1 virus virulence in mice. In this study, we first showed that
      the PA protein of the highly pathogenic avian influenza virus strain CK10 had the
      strongest inhibitory effect on NF-kappaB activation when compared with other
      genes, and that it acted in a dose independent-manner. We then determined the
      critical amino acids of PA that contribute to this effect. Furthermore, PA also
      inhibited NF-kappaB-regulated inflammatory factors, including IL-6, IL-2, Nos-2
      and TNF-alpha. However, the inhibitory effect on NF-kappaB activation mediated by
      PA was not associated with nuclear translocation of p65.

PMID- 28744592
TI  - Examining the Effects of Religious Attendance on Resilience for Older Adults.
AB  - Growing older often brings hardship, adversity, and even trauma. Resilience is a
      broad term used to describe flourishing despite adversity. To date, resilience
      and the connections to religion have not been well studied, despite compelling
      evidence that religious practice can promote psychological health. This research
      examines the role that religion plays in promoting resilience among older adults.
      Research questions include: (a) What is the relationship between religion and
      trait resilience? and (b) Does religion promote resilient reintegration following
      traumatic life events? Results indicate that religious service attendance is tied
      to higher levels of trait resilience and that both service attendance and trait
      resilience directly predict lower levels of depression and higher rates of
      resilient reintegration following traumatic life events. Findings suggest that
      religious service attendance has protective properties that are worthy of
      consideration when investigating resilience.

PMID- 28744593
TI  - Post-hospitalization Treatment Regimen and Readmission for C. difficile Colitis
      in Medicare Beneficiaries.
AB  - BACKGROUND: C. difficile (CDI) has surpassed methicillin-resistant staph aureus
      as the most common nosocomial infection with recurrence reaching 30% and the
      elderly being disproportionately affected. We hypothesized that post-discharge
      antibiotic therapy for continued CDI treatment reduces readmissions. STUDY
      DESIGN: We queried a 5% random sample of Medicare claims (2009-2011 Part A and
      Part D; n = 864,604) for hospitalizations with primary or secondary diagnosis of
      CDI. We compared demographics, comorbidities, and post-discharge CDI treatment
      (no CDI treatment, oral metronidazole only, oral vancomycin only, or both)
      between patients readmitted with a primary diagnosis of CDI within 90 days and
      patients not readmitted for any reason using univariate tests of association and
      multivariable models. RESULTS: Of 7042 patients discharged alive, 945 were
      readmitted <=90 days with CDI (13%), while 1953 were not readmitted for any
      reason (28%). Patients discharged on dual therapy had the highest rates of
      readmission (50%), followed by no post-discharge CDI treatment (43%), vancomycin
      only (28%), and metronidazole only (19%). Patients discharged on only
      metronidazole (OR 0.28) or only vancomycin (OR 0.42) had reduced odds of 90-day
      readmission compared to patients discharged on no CDI treatment. Patients
      discharged on dual therapy did not vary in odds of readmission. CONCLUSIONS:
      Thirteen percent of patients discharged with CDI are readmitted within 90 days.
      Patients discharged with single-drug therapy for CDI had lower readmission rates
      compared to patients discharged on no ongoing CDI treatment suggesting that short
      term monotherapy may be beneficial in inducing eradication and preventing
      relapse. Half of patients requiring dual therapy required readmission, suggesting
      patients with symptoms severe enough to warrant discharge on dual therapy may
      benefit from longer hospitalization.

PMID- 28744594
TI  - Tube Thoracostomy Complications: More to Learn.

PMID- 28744595
TI  - Acute Appendicitis: Still a Surgical Disease? Results from a Propensity Score
      Based Outcome Analysis of Conservative Versus Surgical Management from a
      Prospective Database.

PMID- 28744596
TI  - A Novel Prognostic Scoring System Using Inflammatory Response Biomarkers for
      Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: We describe a novel scoring system, namely the inflammatory response
      biomarker (IRB) score. The aim of this study is to evaluate the clinical value of
      IRB score in patients undergoing curative resection for esophageal squamous cell
      carcinoma (SCC). METHODS: We retrospectively reviewed patients who underwent
      curative esophagectomy. We evaluated IRB score in both non-elderly (<70 years)
      and elderly (>=70 years) SCC patients. The IRB score was determined as follows: a
      high lymphocyte-to-monocyte ratio (LMR) (>4), a high neutrophil-to-lymphocyte
      ratio (NLR) (>1.6), and a low platelet-to-lymphocyte ratio (PLR) (<147) were each
      scored as 1, and the remaining values were scored as 0; the individual scores
      were then summed to produce the IRB score (range 0-3). RESULTS: Univariate
      analyses demonstrated that the TNM pStage (p < 0.0001), tumor size (p = 0.002),
      LMR (p = 0.0057), PLR (p = 0.0328) and IRB score (p = 0.0003) were significant
      risk factors for a worse prognosis. On multivariate analysis, the TNM pStage (p <
      0.0001) and IRB score (p = 0.0227) were independently associated with worse
      prognosis in overall patients. Among non-elderly patients, multivariate analyses
      demonstrated that the pStage (p = 0.0015) and IRB score (p = 0.0356) were
      independent risk factors for a worse prognosis. Among elderly patients,
      multivariate analysis demonstrated that the pStage (p = 0.0016), and IRB score (p
      = 0.0102) were independent risk factors for a worse prognosis. CONCLUSION: The
      present study provides evidence that the preoperative IRB score can be considered
      a promising independent prognostic factor of cancer-specific survival in patients
      undergoing curative resection for SCC, and that its predictive ability is useful
      in both non-elderly and elderly patients.

PMID- 28744597
TI  - Non-invasive liver fibrosis assessment and HCV treatment initiation within a
      systematic screening program in HIV/HCV coinfected patients.
AB  - BACKGROUND AND AIM: Hepatitis C virus (HCV) therapy should be considered without
      delay in all patients with significant (SIGFIB) or advanced liver fibrosis
      (ADVFIB). We aimed to investigate the rates of treatment initiation with
      interferon-free regimens within a screening program for SIGFIB/ADVFIB in human
      immunodeficiency virus/HCV coinfected patients (HIV/HCV). METHODS: The FIB-4 was
      calculated in all HIV/HCV from 2014-2016. HIV/HCV were counselled by the HIV
      clinic and referred to the Division of Gastroenterology and Hepatology for
      transient elastography (TE) and evaluation for HCV therapy. Patients were
      stratified by FIB-4 of </>=1.45 (established cut-off for ruling out ADVFIB) and
      SIGFIB/ADVFIB were defined by liver stiffness >7.1 kPa/>9.5 kPa, respectively.
      RESULTS: Among 1348 HIV+ patients, 16% (210/1348) had detectable HCV-RNA. One
      hundred HIV/HCV had a FIB-4 >=1.45. Among these, 57% (57/100) underwent TE. The
      majority of these patients had SIGFIB (75%; 43/57) or ADVFIB (37%; 21/57),
      however, interferon-free treatment was initiated in only 56% (24/43). In
      addition, fifty-two percent (57/110) of HIV/HCV with FIB-4 <1.45 underwent TE.
      Interestingly, 40% (23/57) and 18% (10/57) of these patients showed SIGFIB or
      even ADVFIB, respectively, and 78% (18/23) finally received interferon-free
      treatment. Overall, only 20% (42/210) of HIV/HCV received interferon-free
      treatment. CONCLUSION: FIB-4 was not useful for ruling out SIGFIB/ADVFIB in our
      cohort of HIV/HCV. Treatment was initiated only in a small proportion (20%) of
      HIV/HCV during the first 2 years of interferon-free treatment availability,
      although the observed proportion of patients with SIGFIB (assessed by TE) was
      considerably higher (58%). Thus, it requires the ongoing combined efforts of both
      HIV and HCV specialists to increase treatment uptake rates in this special
      population.

PMID- 28744598
TI  - Prof. Walther H. Wernsdorfer (1928-2016).

PMID- 28744599
TI  - Use of Minicameras to Improve Operative Procedure in Security Forces.
AB  - The aim of the present study was to analyze pistol and compact rifle marksmanship
      in close quarter combat (CQC). There is currently a controversy about what weapon
      is most appropriate to use in CQC, short weapon as pistols or long weapons as
      rifle. Forty two participants conducted two close quarter combat simulations, one
      with pistol and one with compact rifle. Marksmanship and time to cover the
      simulation were measured. Data obtained showed no significant differences between
      pistol and compact rifle. In addition, it was observed a tendency to obtain
      higher scores with compact rifle, probably be due to the higher stability
      provided in the shot action. Compact rifle could be an effective election in
      actual theaters of operation in which asymmetrical and symmetrical combat are
      combined and also in police interventions due to compact rifle provide higher
      fire power and range and obtained the same shooting performance than pistol. To
      the best of our knowledge this is the first study that provides empirical data to
      solve the discussion about the efficiency of the use of rifle and pistol in close
      quarter combat in military and police interventions. These results could be used
      to improve the military and police interventions efficiency.

PMID- 28744600
TI  - Excess of all-cause mortality after a fracture in type 2 diabetic patients: a
      population-based cohort study.
AB  - : Post-fracture mortality in type 2 diabetes mellitus (T2DM) patients has been
      poorly studied. We report an absolute and relative excess all-cause mortality
      following a fracture in these patients compared to non-diabetic patients.
      INTRODUCTION: T2DM and osteoporotic fractures are independently associated with a
      reduced lifespan, but it is unknown if T2DM confers an excess post-fracture
      mortality compared to non-diabetic fracture patients. We report post-fracture all
      cause mortality according to T2DM status. METHODS: This is a population-based
      cohort study using data from the SIDIAP database. All >=50 years old T2DM
      patients registered in SIDIAP in 2006-2013 and two diabetes-free controls matched
      on age, gender, and primary care center were selected. Study outcome was all
      cause mortality following incident fractures. Participants were followed from
      date of any fracture (AF), hip fracture (HF), and clinical vertebral fracture
      (VF) until the earliest of death or censoring. Cox regression was used to
      calculate mortality according to T2DM status after adjustment for age, gender,
      body mass index, smoking, alcohol intake, and previous ischemic heart and
      cerebrovascular disease. RESULTS: We identified 166,106 T2DM patients and 332,212
      non-diabetic, of which 11,066 and 21,564, respectively, sustained a fracture and
      were then included. Post-fracture mortality rates (1000 person-years) were (in
      T2DM vs non-diabetics) 62.7 vs 49.5 after AF, 130.7 vs 112.7 after HF, and 54.9
      vs 46.2 after VF. Adjusted HR (95% CI) for post-AF, post-HF, and post-VF
      mortality was 1.30 (1.23-1.37), 1.28 (1.20-1.38), and 1.20 (1.06-1.35),
      respectively, for T2DM compared to non-diabetics. CONCLUSIONS: T2DM patients have
      a 30% increased post-fracture mortality compared to non-diabetics and a
      remarkable excess in absolute mortality risk. More research is needed on the
      causes underlying such excess risk, and on the effectiveness of measures to
      reduce post-fracture morbi-mortality in T2DM subjects.

PMID- 28744601
TI  - 24-hour profile of serum sclerostin and its association with bone biomarkers in
      men.
AB  - : The osteocyte's role in orchestrating diurnal variations in bone turnover
      markers (BTMs) is unclear. We identified no rhythm in serum sclerostin (osteocyte
      protein). These results suggest that serum sclerostin can be measured at any time
      of day and the osteocyte does not direct the rhythmicity of other BTMs in men.
      INTRODUCTION: The osteocyte exerts important effects on bone remodeling, but its
      rhythmicity and effect on the rhythms of other bone cells are not fully
      characterized. The purpose of this study was to determine if serum sclerostin
      displays rhythmicity over a 24-h interval, similar to that of other bone
      biomarkers. METHODS: Serum sclerostin, FGF-23, CTX, and P1NP were measured every
      2 h over a 24-h interval in ten healthy men aged 20-65 years. Maximum likelihood
      estimates of the parameters in a repeated measures model were used to determine
      if these biomarkers displayed a diurnal, sinusoidal rhythm. RESULTS: No
      discernible 24-h rhythm was identified for sclerostin (p = 0.99) or P1NP (p =
      0.65). CTX rhythmicity was confirmed (p < 0.001), peaking at 05:30 (range 01:30
      07:30). FGF-23 levels were also rhythmic (p < 0.001), but time of peak was
      variable (range 02:30-11:30). The only significant association identified between
      these four bone biomarkers was for CTX and P1NP mean 24-h metabolite levels (r =
      0.65, p = 0.04). CONCLUSIONS: Sclerostin levels do not appear to be rhythmic in
      men. This suggests that in contrast to CTX, serum sclerostin could be measured at
      any time of day. The 24-h profiles of FGF-23 suggest that a component of
      osteocyte function is rhythmic, but its timing is variable. Our results do not
      support the hypothesis that osteocytes direct the rhythmicity of other bone
      turnover markers (CTX), at least not via a sclerostin-mediated mechanism.

PMID- 28744602
TI  - Depression, Metabolic Syndrome, and Locus of Control in Arab Americans Living in
      the DC Metropolitan Area: A Structural Equation Model.
AB  - Arab Americans have high prevalences of metabolic syndrome (MetS) and depression.
      Depression and external locus of control (LOC) may worsen MetS. We examined the
      relationship between depression and MetS with a convenience sample of 136 Arab
      Americans living in the Washington, DC, metropolitan area. Participants were
      surveyed with the Multidimensional Health Locus of Control questionnaire and the
      Center of Epidemiological Studies-Depression scale. Laboratory measurements were
      collected based on the components of MetS. A structural equation model was used
      to explore the relationship between MetS and depression through analysis of LOC.
      MetS was significantly correlated with external LOC (powerful others and chance),
      and depression was correlated with a weak internal LOC. Future study of the
      effect of LOC on health outcomes in Arab Americans may be used to mitigate MetS
      and depression in this population.

PMID- 28744603
TI  - Patterns of metastatic progression after definitive radiation therapy for early
      stage and locally advanced non-small cell lung cancer.
AB  - Current preclinical models of metastatic disease (particularly oligometastases)
      suggest that metastases appear in a hierarchical order. We attempted to identify
      systematic patterns of metastasis in non-small cell lung cancer (NSCLC) after
      radiation therapy (XRT). We analyzed 1074 patients treated from 12/21/1998
      through 8/20/2012 with >=60 Gy definitive radiation for initially non-metastatic
      NSCLC. Location and time of metastases were recorded. Regional nodal failure was
      noted, as was subsequent distal failure. For further analysis, we considered only
      the five most common sites of metastasis (bone, brain, liver, adrenal, and lung).
      Metastatic progression over time was defined and patterns elucidated with Chi
      square tests. Histologic findings were analyzed with Wilcoxon rank sum tests. A
      significant multistep linear progression was not apparent. Having a first
      metastasis in lung or bone was associated with respective 16% (median 2.4 months)
      and 15% likelihoods (median 7.9 months) of secondary brain metastasis. Initial
      metastasis in the brain led to metastasis in another organ 29.3% of the time,
      most often in the lung, bone, and liver (medians 3.6, 7.9, and 3.1 months).
      Adenocarcinoma was more likely than squamous to metastasize to the brain (18 vs.
      9%) and any of the five major sites (41 vs. 27%). We did not appreciate dominant
      patterns suggesting a multi-step hierarchical order of metastasis. Rather, our
      findings suggest that certain subgroups may develop different patterns of spread
      depending on a variety of factors.

PMID- 28744604
TI  - Methylphenidate and Atomoxetine-Responsive Prefrontal Cortical Genetic Overlaps
      in "Impulsive" SHR/NCrl and Wistar Rats.
AB  - Impulsivity, the predisposition to act prematurely without foresight, is
      associated with a number of neuropsychiatric disorders, including attention
      deficit/hyperactivity disorder (ADHD). Identifying genetic underpinnings of
      impulsive behavior may help decipher the complex etiology and neurobiological
      factors of disorders marked by impulsivity. To identify potential genetic factors
      of impulsivity, we examined common differentially expressed genes (DEGs) in the
      prefrontal cortex (PFC) of adolescent SHR/NCrl and Wistar rats, which showed
      marked decrease in preference for the large but delayed reward, compared with
      WKY/NCrl rats, in the delay discounting task. Of these DEGs, we examined drug
      responsive transcripts whose mRNA levels were altered following treatment (in
      SHR/NCrl and Wistar rats) with drugs that alleviate impulsivity, namely, the ADHD
      medications methylphenidate and atomoxetine. Prefrontal cortical genetic overlaps
      between SHR/NCrl and Wistar rats in comparison with WKY/NCrl included genes
      associated with transcription (e.g., Btg2, Fos, Nr4a2), synaptic plasticity
      (e.g., Arc, Homer2), and neuron apoptosis (Grik2, Nmnat1). Treatment with
      methylphenidate and/or atomoxetine increased choice of the large, delayed reward
      in SHR/NCrl and Wistar rats and changed, in varying degrees, mRNA levels of
      Nr4a2, Btg2, and Homer2, genes with previously described roles in
      neuropsychiatric disorders characterized by impulsivity. While further studies
      are required, we dissected potential genetic factors that may influence
      impulsivity by identifying genetic overlaps in the PFC of "impulsive" SHR/NCrl
      and Wistar rats. Notably, these are also drug-responsive transcripts which may be
      studied further as biomarkers to predict response to ADHD drugs, and as potential
      targets for the development of treatments to improve impulsivity.

PMID- 28744605
TI  - Interaction between Parental Education and Twin Correlations for Cognitive
      Ability in a Norwegian Conscript Sample.
AB  - We examine a sample of Norwegian twin conscripts for evidence of an interaction
      between parental education and the heritability of general cognitive ability
      (GA). Ability scores were obtained on 1706 pairs of twins who were conscripted
      into the Norwegian Armed Forces between 1931and 1960. Education scores were
      available for mothers and fathers; the majority of the parents had less than a
      high school education. GA scores were heteroscadistic with respect to mid-parent
      education, with reduced variability at higher levels of education. Both MZ and DZ
      twin correlations for GA were linearly and negatively related to mid-parent
      education, DZ twins substantially more so. When the model was extended to an ACE
      model consisting of standardized positive ACE variance components, the
      modification appeared to disappear. Further analysis revealed that this occurred
      because the steep decline of DZ twin correlations with increasing mid-parent
      education resulted in a violation of the classical twin model for much of the
      parameter space. Other phenomena that might result in large declines in DZ twin
      correlations are considered, along with implications for other studies of
      socioeconomic interactions with the heritability of GA in European samples.

PMID- 28744606
TI  - Rescue bypass for the treatment of pseudoaneurysm on the distal anterior cerebral
      artery: a case report of vertical side-to-side anastomosis of the distal
      callosomarginal artery-pericallosal artery.
AB  - Pseudoaneurysm on the distal anterior cerebral artery (ACA) is rare but
      potentially fatal. It usually cannot be treated with typical treatment
      modalities. A 47-year-old female patient was diagnosed with a ruptured aneurysm
      on the pericallosal artery (PerA). During surgical exploration, it was found to
      be a pseudoaneurysm and could not be treated with clipping. We performed surgical
      trapping of the involved segment of the proximal PerA followed by side-to-side
      anastomosis between the ipsilateral PerA and the callosomarginal artery. The
      patient recovered without any neurologic deficit. This new method of anastomosis
      could be an alternative option.

PMID- 28744607
TI  - Music-space associations are grounded, embodied and situated: examination of
      cello experts and non-musicians in a standard tone discrimination task.
AB  - In recent research, a systematic association of musical pitch with space has been
      described in the so-called Spatial-Pitch-Association-of-Response Codes-effect
      (SPARC). Typically, high pitch is associated with upper/right and low pitch with
      lower/left space. However, a theoretical classification of these associations
      regarding their experiential sources is difficult. Therefore, we applied a
      theoretical framework of numerical cognition classifying similar Space-Associated
      Response Codes (SARC) effects according to their groundedness, embodiedness and
      situatedness. We tested these attributes with a group of non-musicians and with a
      group of highly skilled cello players playing high tones with lower hand
      positions (i.e., reverse SPARC alignment) in a standard SPARC context of a piano
      and a reversed SPARC context of a cello. The results showed that SPARC is
      grounded, in general. However, for cello player SPARC is also situated and
      embodied. We conclude that groundedness, embodiedness and situatedness provide
      general characteristics of mapping cognitive representations to space.

PMID- 28744608
TI  - [Reconstruction of osseous defects using the Masquelet technique].
AB  - The Masquelet procedure or induced membrane technique presents a treatment option
      for relatively large osseous defects, e.g. after trauma, tumour resection or
      osteomyelitis even in the presence of unfavourable soft tissues. Initially
      developed at the end of the last century by the French surgeon Masquelet, the
      technique relies on a bioactive membrane that forms a foreign body reaction
      around a cement spacer. This spacer is implanted in the residual defect after
      rigorous debridement of bone and soft tissue during a first-stage procedure. A
      second-stage intervention is performed 1-2 months later with removal of the
      spacer under preservation of the membrane that has since formed around the
      cement. The membrane acts as an internal bioreactor exerting its effect via a
      rich vascularization and secretion of growth and differentiation factors. The
      void within the membrane is filled with an autologous cancellous graft. After
      adequate stabilisation using standard techniques, a gradual corticalisation of
      the graft can be observed over the duration of several months, with remodelling
      in the long-term course.The following article describes the original technique,
      our preferred approach including indication, surgical technique and postoperative
      follow-up. Additionally, the biological background and clinical tips and tricks
      are presented.

PMID- 28744609
TI  - [Autologous fibula transplantation for reconstruction of bone defects].
AB  - The reconstruction of large bone defects following tumor resection, trauma or
      infection is difficult and subject to individual preferences of each surgeon.
      Free autologous fibula grafts are a reliable biological treatment method, whereas
      both a vascularised and a non-vascularised transplantation is possible. The use
      of either treatment option - vascularised or non-vascularised - is accompanied by
      individual advantages and/or disadvantages that should be taken into
      consideration during the preoperative planning process. Vascularised fibula
      transplants should be used especially for the reconstruction of large segmental
      defects and in patients, in whom adjuvant chemo- and/or radiation therapy is to
      be administered. Non-vascularised fibula grafts - which offer the advantage of a
      certain regeneration potential at the donor site as well as a shorter operation
      time - might be beneficial for bridging hemicortical defects and segmental
      defects with good soft tissue coverage.

PMID- 28744611
TI  - Relationship between heart rate and quiescent interval of the cardiac cycle in
      children using MRI.
AB  - BACKGROUND: Imaging the heart in children comes with the challenge of constant
      cardiac motion. A prospective electrocardiography-triggered CT scan allows for
      scanning during a predetermined phase of the cardiac cycle with least motion.
      This technique requires knowing the optimal quiescent intervals of cardiac cycles
      in a pediatric population. OBJECTIVE: To evaluate high-temporal-resolution cine
      MRI of the heart in children to determine the relationship of heart rate to the
      optimal quiescent interval within the cardiac cycle. MATERIALS AND METHODS: We
      included a total of 225 consecutive patients ages 0-18 years who had high
      temporal-resolution cine steady-state free-precession sequence performed as part
      of a magnetic resonance imaging (MRI) or magnetic resonance angiography study of
      the heart. We determined the location and duration of the quiescent interval in
      systole and diastole for heart rates ranging 40-178 beats per minute (bpm). We
      performed the Wilcoxon signed rank test to compare the duration of quiescent
      interval in systole and diastole for each heart rate group. RESULTS: The duration
      of the quiescent interval at heart rates <80 bpm and >90 bpm was significantly
      longer in diastole and systole, respectively (P<.0001 for all ranges, except for
      90-99 bpm [P=.02]). For heart rates 80-89 bpm, diastolic interval was longer than
      systolic interval, but the difference was not statistically significant (P=.06).
      We created a chart depicting optimal quiescent intervals across a range of heart
      rates that could be applied for prospective electrocardiography-triggered CT
      imaging of the heart. CONCLUSION: The optimal quiescent interval at heart rates
      <80 bpm is in diastole and at heart rates >=90 bpm is in systole. The period of
      quiescence at heart rates 80-89 bpm is uniformly short in systole and diastole.

PMID- 28744612
TI  - Reamer-Irrigator-Aspirator bone graft harvesting for treatment of segmental bone
      loss: analysis of defect volume as independent risk factor for failure.
AB  - INTRODUCTION: The management of segmental bone loss poses a significant clinical
      challenge. The purpose of this study was to conduct a retrospective evaluation of
      our experience in treating segmental bone loss, using Reamer-Irrigator-Aspirator
      (RIA)-harvested autologous bone graft. MATERIALS AND METHODS: Between June 2008
      and March 2015, 81 patients were treated with the RIA technique for multiple
      purposes. Inclusion criteria for this study were skeletal mature patients with
      segmental bone loss, due to acute trauma or non-union, who were treated with RIA
      harvested bone graft. Exclusion criteria were skeletal immaturity, pathological
      fractures and indications for the RIA system other than bone graft harvesting.
      The primary outcome parameter was clinical and radiographical bone healing.
      RESULTS: During the study period, 72 patients met the inclusion criteria. In
      total, 39 patients (54.2%) were classified as having clinical and radiographical
      bone healing. Although univariate analysis could not reveal any significant
      influence of specific risk factors to predict the outcome, there was a trend
      towards statistical significance for defect volume. Further analysis indeed
      revealed that smaller defect volumes (< 8 cm3) had a lower risk of non-union.
      CONCLUSIONS: In approximately half of our study population, the use of the RIA
      technique for autologous bone graft harvesting in cases of segmental bone loss
      resulted in a successful outcome with bone healing. Defect size seems to be a
      critical issue regarding the outcome. Although our results are less promising
      than previously published, the RIA technique has its place in the treatment
      algorithm of segmental bone defects.

PMID- 28744613
TI  - Development of functionalized polyetherimide/polyvinylpyrrolidone membranes for
      application in hemodialysis.
AB  - The present study aimed to synthesize membranes for hemodialysis based on
      polyetherimide (PEI) and polyvinylpyrrolidone (PVP), with chemical immobilization
      of heparin on its surface to increase blood compatibility. The synthesized
      PEI/PVP membranes were characterized by morphological analysis and transport
      properties, as well by infrared spectroscopy (FT-IR), protein adsorption, contact
      angle, activated partial thromboplastin time (aPTT), and platelet adhesion.
      Hydraulic permeability of the synthesized PEI membranes were comparable to those
      of current high flux clinical membranes; values of diffusive permeability and
      rejection for typical solutes were similar to those reported in literature. The
      immobilization of heparin, in turn, resulted in more hydrophilic membranes, with
      insignificant protein adsorption and platelet adhesion (as opposed to actual
      clinical membranes), indicating anti-thrombogenic characteristics as confirmed by
      increased aPTT.

PMID- 28744614
TI  - Enhanced bone formation in the vicinity of porous beta-TCP scaffolds exhibiting
      slow release of collagen-derived tripeptides.
AB  - It has been experimentally proven that orally ingested collagen-derived
      tripeptides (Ctp) are quickly absorbed in the body and effectively promote the
      regeneration of connective tissues including bone and skin. Ctp are capable to
      activate osteoblasts and fibroblasts, which eventually promotes tissue
      regeneration. Based on these findings, a hypothesis was formulated in this study
      that direct delivery of Ctp to bone defect would also facilitate tissue
      regeneration as well as oral administration. To test the hypothesis, we prepared
      a bone augmentation material with the ability to slowly release Ctp, and
      investigated its in vivo bone regeneration efficacy. The implant material was
      porous beta-tricalcium phosphate (beta-TCP) scaffold which was coated with a co
      precipitated layer of bone-like hydroxyapatite and Ctp. The beta-TCP was
      impregnated with approximately 0.8%(w/w) Ctp. Then, the Ctp-modified beta-TCP was
      implanted into bone defects of Wistar rats to evaluate in vivo efficacy of Ctp
      directly delivered from the material to the bone defects. The control was
      pristine porous beta-TCP. In vitro tests showed that Ctp were steadily released
      from the co-precipitated layer for approximately two weeks. The Ctp-modified
      scaffolds significantly promoted new bone formation in vivo in their vicinity as
      compared with pristine beta-TCP scaffolds; 6 weeks after the implantation, Ctp
      modified scaffolds promoted twice as much bone formation as the control implants.
      Consequently, we achieved the slow and steady release of Ctp, and found that
      direct delivery of Ctp from implant materials was effective for bone regeneration
      as well as oral administration. A beta-TCP scaffold capable of slowly releasing
      bone-enhancing substances significantly promoted bone formation.

PMID- 28744616
TI  - Subserosal uterine injection of blue dye for the identification of the sentinel
      node in patients with endometrial cancer: a feasibility study.
AB  - OBJECTIVE: To define the detection rate, sensitivity, and negative predictive
      value (NPV) of the sentinel node technique in patients with endometrial cancer.
      METHODS: Patients with endometrial cancer after informed consent underwent
      subserosal injection of blue dye during hysterectomy in a tertiary gynae/oncology
      department between 2010 and 2014. The procedure was performed in all cases by the
      same team including two gynae/oncologist consultants and one trainee. All
      relevant perioperative clinicopathological characteristics of the population were
      recorded prospectively. The identified sentinel nodes were removed separately and
      a completion bilateral pelvic lymphadenectomy followed in all cases. Simple
      statistics were used to calculate the sensitivity and NPV of the method on per
      patient basis. RESULTS: Fifty-four patients were included in this study. At least
      one sentinel node was mapped in 46 patients yielding a detection rate of 85.2%.
      Bilateral detection of sentinel nodes was accomplished in only 31 patients
      (57.4%). The mean number of sentinel nodes was 2.6 per patient and the commonest
      site of identification was the external iliac artery and vein area (66%). Six
      patients (11%) had a positive lymph node, and in five of them, this was the
      sentinel one yielding a sensitivity of 83.3% and an NPV of 97.5%. The overall
      detection rate improved significantly after the first 15 cases; however, this was
      not the case for the bilateral detection rate. CONCLUSION: Our study is in
      accordance with previous studies of sentinel node in endometrial cancer and
      further demonstrates and enhances the confidence in the technique. In the current
      era of an ongoing debate on whether a systematic lymphadenectomy in patients with
      endometrial cancer is still necessary, we believe that the sentinel node is an
      acceptable alternative and should be applied routinely in tertiary centres
      following a strict algorithm.

PMID- 28744615
TI  - Stem cell-mediated functionalization of titanium implants.
AB  - Prosthetic implants are used daily to treat edentulous people and to restore
      mobility in patients affected by skeletal defects. Titanium (Ti) is the material
      of choice in prosthetics, because it can form a stable bond with the surrounding
      bone following implantation-a process known as osseointegration. Yet, full
      integration of prosthetic implants takes time, and fails in clinical situations
      characterized by limited bone quantity and/or compromised regenerative capacity,
      and in at-risk patients. Intense research efforts are thus made to develop new
      implants that are cost-effective, safe, and suited to every patient in each
      clinical situation. In this study, we tested the possibility to functionalize Ti
      implants using stem cells. Human induced pluripotent stem cell-derived
      mesenchymal progenitor (iPSC-MP) cells were cultured on Ti model disks for 2
      weeks in osteogenic conditions. Samples were then treated using four different
      decellularization methods to wash off the cells and expose the matrix. The
      functionalized disks were finally sterilized and seeded with fresh human iPSC-MP
      cells to study the effect of stem cell-mediated surface functionalization on cell
      behavior. The results show that different decellularization methods produce
      diverse surface modifications, and that these modifications promote proliferation
      of human iPSC-MP cells, affect the expression of genes involved in development
      and differentiation, and stimulate the release of alkaline phosphatase. Cell
      mediated functionalization represents an attractive strategy to modify the
      surface of prosthetic implants with cues of biological relevance, and opens
      unprecedented possibilities for development of new devices with enhanced
      therapeutic potential.

PMID- 28744617
TI  - Palm Olein Emulsion: a Novel Vehicle for Topical Drug Delivery of Betamethasone
      17-Valerate.
AB  - This study aims to investigate the use of palm olein as the oil phase for
      betamethasone 17-valerate (BV) emulsions. The physicochemical properties of the
      formulations were characterized. In vitro drug release study was performed with
      the Hanson Vertical Diffusion Cell System; the samples were quantified with HPLC
      and the results were compared with commercial products. Optimized emulsion
      formulations were subjected to stability studies for 3 months at temperatures of
      4, 25, and 40 degrees C; the betamethasone 17-valerate content was analyzed using
      HPLC. The formulations produced mean particle size of 2-4 MUm, viscosities of 50
      250 mPa.s, and zeta potential between -45 and -68 mV. The rheological analyses
      showed that the emulsions exhibited pseudoplastic and viscoelastic behavior. The
      in vitro release of BV from palm olein emulsion through cellulose acetate was 4.5
      times higher than that of commercial products and more BV molecules deposited in
      rat skin. Less than 4% of the drug was degraded in the formulations during the 3
      month period when they were subjected to the three different temperatures. These
      findings indicate that palm olein-in-water emulsion can be an alternative vehicle
      for topical drug delivery system with superior permeability.

PMID- 28744618
TI  - [Image enhancement for Germany's urologists : From strategy workshop to the
      creation of the "urology brand name"].

PMID- 28744619
TI  - Optimal minimally invasive surgical procedure for gastric submucosal tumors.
AB  - BACKGROUND: Laparoscopic wedge resection (LWR) is widely performed for managing
      gastric submucosal tumors (SMTs). Despite the development of novel procedures
      such as laparoscopy-endoscopy cooperative surgery (LECS) and nonexposed
      endoscopic wall-inversion surgery (NEWS), the most appropriate surgical
      intervention for gastric SMTs remains unclear. METHODS: We retrospectively
      reviewed patient characteristics, surgical outcomes, postoperative courses,
      results of histopathological examinations, and surgical costs of 71 consecutive
      patients who underwent LWR, LECS, or NEWS for gastric SMTs from January 2010 to
      June 2016 in our institute. RESULTS: LWR, LECS, and NEWS were performed in 31,
      14, and 26 cases, respectively. Patient backgrounds were comparable between
      groups. LWR was not performed for esophagogastric (E-G) junction tumors to avoid
      postoperative stricture, and LECS was not performed for ulcerated tumors to
      prevent tumor dissemination. NEWS was considered for tumors smaller than 3 cm for
      transoral extraction. Resected specimen area of the LWR group was significantly
      larger than that of the other groups. Further, the LWR group had a significantly
      higher complication rate. Compared to the LECS group, postoperative serum C
      reactive protein level was significantly lower and postoperative hospitalization
      was significantly shorter in the NEWS group. Also, operation costs were
      significantly lower in the NEWS group. CONCLUSIONS: The surgical procedure for
      gastric SMTs must be carefully chosen according to tumor size, location, and
      presence or absence of ulceration. For selected patients, NEWS is suggested to be
      an appropriate option for the treatment of gastric SMTs.

PMID- 28744620
TI  - Persistent perceptual delay for active head movement onset relative to sound
      onset with and without vision.
AB  - Knowing when the head moves is crucial information for the central nervous system
      to maintain a veridical representation of the self in the world for perception
      and action. Previous studies have shown that active head movement onset has to
      precede a sound by approximately 80 ms to be perceived as simultaneous,
      suggesting that the perceived timing of head movement is slow. However, this
      research was conducted with closed eyes. Given that visual information is
      available for most natural head movements, could perceptual delays in head
      movement onset be related to removing vision? Here, we examined whether visual
      information affects the perceived timing of active head movement onset.
      Participants performed a series of temporal order judgment tasks between their
      active head movement and an auditory tone presented at various stimulus onset
      asynchronies. Visual information was either absent (eyes closed) or present while
      either maintaining fixation on an earth or head-fixed target in the dark or in
      the light. Results show that head movement onset has to precede a sound by ~76 ms
      with eyes closed confirming previous work. The results also suggest that head
      movement onset must still precede a sound when fixating targets in the dark with
      a trend for the head having to move with less lead time with visual information
      and with the vestibulo-ocular reflex active or suppressed (~70 to 48 ms).
      Together, these results suggest that the perception of head movement onset is
      persistently delayed and is not fully resolved even with full field visual input.

PMID- 28744621
TI  - No evidence for toxicity after long-term photobiomodulation in normal non-human
      primates.
AB  - In this study, we explored the effects of a longer term application, up to 12
      weeks, of photobiomodulation in normal, naive macaque monkeys. Monkeys (n = 5)
      were implanted intracranially with an optical fibre device delivering
      photobiomodulation (red light, 670 nm) to a midline midbrain region. Animals were
      then aldehyde-fixed and their brains were processed for immunohistochemistry. In
      general, our results showed that longer term intracranial application of
      photobiomodulation had no adverse effects on the surrounding brain parenchyma or
      on the nearby dopaminergic cell system. We found no evidence for
      photobiomodulation generating an inflammatory glial response or neuronal
      degeneration near the implant site; further, photobiomodulation did not induce an
      abnormal activation or mitochondrial stress in nearby cells, nor did it cause an
      abnormal arrangement of the surrounding vasculature (endothelial basement
      membrane). Finally, because of our interest in Parkinson's disease, we noted that
      photobiomodulation had no impact on the number of midbrain dopaminergic cells and
      the density of their terminations in the striatum. In summary, we found no
      histological basis for any major biosafety concerns associated with
      photobiomodulation delivered by our intracranial approach and our findings set a
      key template for progress onto clinical trial on patients with Parkinson's
      disease.

PMID- 28744622
TI  - Slowing in reading and picture naming: the effects of aging and developmental
      dyslexia.
AB  - We examined the slowing in vocal reaction times shown by dyslexic (compared to
      control) children with that of older (compared to younger) adults using an
      approach focusing on the detection of global, non-task-specific components. To
      address this aim, data were analyzed with reference to the difference engine
      (DEM) and rate and amount (RAM) models. In Experiment 1, typically developing
      children, children with dyslexia (both attending sixth grade), younger adults and
      older adults read words and non-words and named pictures. In Experiment 2, word
      and picture conditions were presented to dyslexic and control children attending
      eighth grade. In both experiments, dyslexic children were delayed in reading
      conditions, while they were unimpaired in naming pictures (a finding which
      indicates spared access to the phonological lexicon). The reading difficulty was
      well accounted for by a single multiplicative factor while only the residual
      effect of length (but not frequency and lexicality) was present after controlling
      for over-additivity using a linear mixed effects model with random slopes on
      critical variables. Older adults were slower than younger adults across reading
      and naming conditions. This deficit was well described by a single multiplicative
      factor. Thus, while slowing of information processing is limited to orthographic
      stimuli in dyslexic children, it cuts across verbal tasks in older adults.
      Overall, speed differences in groups such as dyslexic children and older adults
      can be effectively described with reference to deficits in domains encompassing a
      variety of experimental conditions rather than deficits in single specific
      task/conditions. The DEM and RAM prove effective in teasing out global vs.
      specific components of performance.

PMID- 28744623
TI  - The Shepard-Risset glissando: music that moves you.
AB  - Sounds are thought to contribute to the perceptions of self-motion, often via
      higher-level, cognitive mechanisms. This study examined whether illusory self
      motion (i.e. vection) could be induced by auditory metaphorical motion
      stimulation (without providing any spatialized or low-level sensory information
      consistent with self-motion). Five different types of auditory stimuli were
      presented in mono to our 20 blindfolded, stationary participants (via a loud
      speaker array): (1) an ascending Shepard-Risset glissando; (2) a descending
      Shepard-Risset glissando; (3) a combined Shepard-Risset glissando; (4) a combined
      adjusted (loudness-controlled) Shepard-Risset glissando; and (5) a white-noise
      control stimulus. We found that auditory vection was consistently induced by all
      four Shepard-Risset glissandi compared to the white-noise control. This
      metaphorical auditory vection appeared similar in strength to the vection induced
      by the visual reference stimulus simulating vertical self-motion. Replicating
      past visual vection findings, we also found that individual differences in
      postural instability appeared to significantly predict auditory vection strength
      ratings. These findings are consistent with the notion that auditory
      contributions to self-motion perception may be predominantly due to higher-level
      cognitive factors.

PMID- 28744624
TI  - Severity of bulimia nervosa and its impact on treatment outcome.

PMID- 28744625
TI  - The role of socioeconomic and region disparity on colorectal cancer screening:
      what matters more in developing countries?

PMID- 28744626
TI  - Spontaneous breathing (SB) using airway pressure-release ventilation (APRV) in
      patients under extracorporeal-membrane oxygenation (ECMO) for acute respiratory
      distress syndrome (ARDS).

PMID- 28744627
TI  - Neurocognitive Treatments for Eating Disorders and Obesity.
AB  - PURPOSE OF REVIEW: Recent research has highlighted executive function and
      neurocognitive deficits among individuals with eating and weight disorders,
      identifying a potential target for treatment. Treatments targeting executive
      function for eating and weight disorders are emerging. This review aims to
      summarize the recent literature evaluating neurocognitive/executive function
      oriented treatments for eating and weight disorders and highlights additional
      work needed in this area. RECENT FINDINGS: Cognitive remediation therapy (CRT)
      for anorexia nervosa has been the most extensively studied neurocognitive
      treatment for eating disorders. Results demonstrate that CRT improves executive
      function and may aid in the reduction of eating disorder symptomatology. Computer
      training programs targeting modifying attention and increasing inhibition are
      targeting reduction of binge eating and weight loss with modest success.
      Neurocognitive treatments are emerging and show initial promise for eating and
      weight disorders. Further research is necessary to determine whether these
      treatments can be used as stand-alone treatments or whether they need to be used
      as an adjunct to or in conjunction with other evidence-based treatments to
      improve outcomes.

PMID- 28744628
TI  - Infection-related hospitalizations after kidney transplantation in children:
      incidence, risk factors, and cost.
AB  - BACKGROUND: Infection is the leading cause of death and hospitalization in renal
      transplant recipients. We describe posttransplant infections requiring
      hospitalization, their risk factors and cost in a national pediatric kidney
      transplantation cohort. METHODS: Data on renal transplant recipients <20 years
      were extracted from the French National Medicoadministrative Hospital Discharge
      database between 2008 and 2013 and matched with the Renal Transplant Database. We
      used Cox regression to study risk factors of hospitalization and calculated the
      instantaneous risk of hospitalization per month for all infections and by
      infection type. RESULTS: Five hundred and ninety-three patients were included,
      and 660 infection-related hospitalizations were identified in 260 patients. The
      leading cause of hospitalization was urinary tract infection (UTI), followed by
      viral infection (16.6 and 15.6 per 100 person-years, respectively). Risk factors
      were younger age at transplantation, high number of HLA mismatches, and use
      cyclosporine rather than tacrolimus as first anticalcineurin treatment. Risk
      factors varied by infection type. Female gender, uropathy, cold ischemia time,
      and cyclosporine were associated with increased risk of UTI, while only age at
      transplantation inversely correlated with virus-related hospitalizations.
      Instantaneous risk of all infections decreased with time, except for
      cytomegalovirus (CMV) infection that displayed a peak at 6 months
      posttransplantation after prophylaxis withdrawal. Total cost of infection-related
      hospitalizations was 1600 kilo-euro (k?) (933 ?/person-years). CONCLUSIONS: This
      study highlights the high burden of infection in transplanted pediatric patients,
      especially the youngest. This should be considered both for pretransplantation
      information and designing procedures aiming to decrease hospitalization rate and
      duration.

PMID- 28744629
TI  - Effect of Progressive Heart Failure on Cerebral Hemodynamics and Monoamine
      Metabolism in CNS.
AB  - Compensated and decompensated heart failure are characterized by different
      associations of disorders in the brain and heart. In compensated heart failure,
      the blood flow in the common carotid and basilar arteries does not change.
      Exacerbation of heart failure leads to severe decompensation and is accompanied
      by a decrease in blood flow in the carotid and basilar arteries. Changes in
      monoamine content occurring in the brain at different stages of heart failure are
      determined by various factors. The functional exercise test showed unequal
      monoamine-synthesizing capacities of the brain in compensated and decompensated
      heart failure. Reduced capacity of the monoaminergic systems in decompensated
      heart failure probably leads to overstrain of the central regulatory mechanisms,
      their gradual exhaustion, and failure of the compensatory mechanisms, which
      contributes to progression of heart failure.

PMID- 28744630
TI  - Effects of Chronic Tobacco Smoking on the Distribution of Tachykinin Receptors in
      Rat Pial Arteries.
AB  - Pial arteries of different diameter were studied in intact rats and after 6-month
      modeling of chronic tobacco smoking in rats. Expression of tachykinin NK1
      receptors in pial arteries was studied by biomicroscopy and immunohistochemical
      methods. Chronic tobacco smoking induced considerable reorganizations of the
      arterial bed. The intensity of changes depended on the diameter of vessels. In
      small pial vessels that directly participate in the blood supply to the brain,
      pronounced vasodilatation and enhanced expression of NK1 receptors in the
      endothelium mediating the effects of substance P were observed; the number of
      these vessels also increased. The intensity of the response to tobacco smoke
      components decreased with increasing vessel diameter.

PMID- 28744631
TI  - Effects of Fullerene Derivatives on Activity of Ca2+-ATPase of the Sarcoplasmic
      Reticulum and cGMP Phosphodiesterase.
AB  - We studied the effects of new water-soluble polysubstituted fullerene C60 (PFD)
      derivatives on activity of Ca2+-Mg2+ ATPase of the sarcoplasmic reticulum and
      cGMP phosphodiesterase. All examined fullerene derivatives inhibited activity of
      both enzymes. For instance, PFD-I, PFD-II, PFD-III, PFD-V, PFD-IX, PFD-X, and PFD
      XI in a concentration of 5*10-5 M completely inhibited hydrolytic and transport
      functions of Ca2+-ATPase. These compounds in a concentration of 5*10-6 suppressed
      active transport of calcium ions by 51+/-5, 77+/-8, 52+/-5, 52+/-5, 100+/-10,
      80+/-8, and 100+/-10%, respectively, and inhibited ATP hydrolysis by 31+/-3, 78+/
      8, 18+/-2, 29+/-3, 78+/-8, 63+/-7, and 73+/-9%, respectively, uncoupling the
      hydrolytic and transport functions of the enzyme. PFD-I noncompetitive and
      reversibly reduced activity of Ca2+-ATPase (Ki=2.3*10-6 M). All the studied
      fullerene derivatives (except for PFD-VII) inhibited cGMP phosphodiesterase by
      more than 80% in concentration of 10-4 M and higher and by more than 50% in
      concentration of 10-5 M. PFD-I is a non-competitive reversible inhibitor of cGMP
      phosphodiesterase (Ki=7*10-6 M). These results allow us to expect antimetastatic,
      antiaggregatory, antihypertensive and vasodilative activity of the studied
      compounds.

PMID- 28744632
TI  - Combinatorial Screening of Peptides, Specific Ligands of Death Receptor DR5.
AB  - Death receptors, in particular DR5, are highly attractive targets of antitumor
      therapy. The major limitation to application of natural death receptor ligands
      (TRAIL) is their non-specific cytotoxicity against normal cells. Since TRAIL can
      also bind decoy receptors (DcR) and prevent induction of apoptosis, the search
      for new DR-specific ligands is a topical issue. In the present study, we used
      combinatorial phage display peptide libraries to select a panel of DR5-binding
      amino acid sequences. A comparative analysis of the selected peptides enabled
      identification of the consensus sequence responsible for binding to DR5.
      Integration of this motif into polypeptide cytotoxic agents may provide targeted
      elimination of malignantly transformed cells.

PMID- 28744633
TI  - The Effectiveness of Cyclic Hydroxamic Acid CHA-5 against Drug-Resistant P388
      Leukemia Strains.
AB  - We studied the effectiveness of cyclic hydroxamic acid CHA-5 against drug
      resistant and multidrug-resistant murine P388 leukemia strains. More than 60%
      mice receiving transplantation of rubomycin-resistant leukemia P388 strain
      survived after CHA-5 monotherapy; combined therapy with CHA-5 and cisplatin was
      also highly effective. Vincristine-resistant tumor was highly sensitive to
      combined treatment with CHA-5 and cyclophosphamide. It should be emphasized that
      standard antitumor agents were used in very low doses in combination therapy and
      CHA-5 significantly potentiated their effect.

PMID- 28744634
TI  - Nephroprotective Effect of EDL Peptide at Acute Injury of Kidneys of Different
      Genesis.
AB  - EDL peptide produced a nephroprotective effect on experimental models gentamycin
      induced nephropathy and ischemia/reperfusion kidney injury in rats. The
      nephroprotective effect of EDL peptide manifested in prevention of oliguria and
      retention azotemia, a decrease in proteinuria and sodium excretion, prevention of
      critical decrease in activities of antioxidant enzymes, suppression of LPO, and
      normalization of energy supply to kidneys cells. Our findings confirm the
      prospects of further studies of the nephroprotective properties of peptide EDL in
      various pathologies of the kidneys.

PMID- 28744635
TI  - Express Estimation of the Biological Age by the Parameters of Body Composition in
      Men and Women over 50 Years.
AB  - Original formulas for rapid assessment of biological age in men and women over 50
      were developed using factor analysis. The proposed technique is mainly based on
      the parameters of the body component composition (fat, musculoskeletal, and
      active cell mass, and specific metabolism) obtained using bioimpedance recording
      widely used in modern medicine and anthropology. The proposed formulas were
      tested on other samples (481 examined subjects). The developed method of express
      estimation of biological age differs from other models by its convenience,
      simplicity, low financial and time costs, and the possibility of using it in mass
      medico-anthropological examinations for identification of individuals/groups with
      accelerated rates of aging.

PMID- 28744636
TI  - NLR2 and TLR3, TLR4, TLR5 Ligands, Injected In Vivo, Improve after 1 h the
      Efficiency of Cloning and Proliferative Activity of Bone Marrow Multipotent
      Stromal Cells and Reduce the Content of Osteogenic Multipotent Stromal Cells in
      CBA Mice.
AB  - Ligands NLR2 (muramyldipeptide) and TLR (bacterial LPS, flagellin, CpG
      dinucleotide, and Poly I:C) and S. typhimurium antigenic complex by 1.5-3-fold
      increase the efficiency of cloning and content of multipotent stromal cells (MSC)
      in the bone marrow of CBA mice as soon as 1 h postinjection. The counts of large
      colonies (150-500 cells) increased by 2.5-3.3 times in comparison with intact
      bone marrow cultures at the expense of a decrease in the number of smaller
      colonies, which attests to enhanced proliferation of stromal cells in the
      colonies. The efficiency of cloning and hence, MSC content in the femoral bone
      decreased by 1.2-1.9 times after 3 h and increased again after 24 h to the level
      1.3-1.5 times higher than the level 1 h postinjection (LPS, Poly I:C, and S.
      typhimurium antigenic complex). The dynamics of bone marrow MSC cloning
      efficiency after 1-3 h corresponded to the dynamics of serum cytokine
      concentrations during the same period. However, the levels of serum cytokines
      after 24 h in general were similar to those in intact mice or were lower. The
      concentrations of osteogenic multipotent stromal cells in the bone marrow
      decreased 2-3-fold after 3 h and thus persisted by 24 h postinjection. Twofold
      (at 24-h interval) and a single injection of S. typhimurium antigenic complex to
      mice led to a significant increase of cloning efficiency, observed as early as
      just 1 h postinjection (1.9 and 1.5 times, respectively). The same picture was
      observed for serum cytokines. On the whole, injections of TLR and NLR ligands and
      of S. typhimurium antigenic complex led to stromal tissue activation within 1 h
      postinjection, this activation consisting in a significant increase of the
      efficiency of cloning and of MSC count in the bone marrow, and also in an
      increase in their proliferative activity and a decrease (after 3 h) of osteogenic
      MSC concentration.

PMID- 28744637
TI  - Antiviral Activity of Lady's Mantle (Alchemilla vulgaris L.) Extracts against
      Orthopoxviruses.
AB  - We studied toxicity and antiviral activity of bioactive substances extracted from
      the roots (ethylacetate extracts) and aerial parts (ethanol extracts) of lady's
      mantle (Alchemilla vilgaris L.). Plant extracts are characterized by low toxicity
      for continuous Vero cell culture, but inhibit the reproduction of orthopoxviruses
      (vaccinia virus and ectromelia virus) in these cells. Of all studied extracts,
      ethylacetate extract from lady's mantle roots characterized by the highest
      content of catechins in comparison with other samples demonstrated the highest
      activity in vitro towards the studied viruses (neutralization index for vaccinia
      and ectromelia viruses were 4.0 and 3.5 lg, respectively). The antiviral effect
      of Alchemilla vulgaris L. extracts was shown to be dose dependent.

PMID- 28744638
TI  - Counts of MSC in the Bone Marrow of Young and Old CBA Mice after a Single
      Exposure to Osteogenic Stimuli (Curettage, BMP-2 Injection) or Antigens (S.
      typhimurium Antigenic Complex) and in Heterotopic Bone Marrow Transplants.
AB  - The efficiency of cloning and the content of multipotent stromal cells (MSC) in
      the femoral bone marrow of intact CBA mice was 1.5 times less in old mice (24-36
      months) than in young ones (2-3 months). The concentration of osteogenic MSC was
      higher in old vs. young mice (42+/-3 vs. 22+/-2%, respectively). Changes in the
      total counts of MSC and concentrations of osteogenic MSC in response to
      osteogenic (curettage, BMP-2) and immunogenic stimuli (S. typhimurium antigenic
      complex) were similar in young and old mice in comparison with intact controls of
      respective age. The counts of the total pool of bone marrow MSC and pool of
      osteogenic MSC in response to osteogenic stimuli were 1.5-2 times less in old vs.
      young mice. This difference seemed to be a result of age-specific decrease of
      their bone marrow count but not of age-specific decrease of the MSC functional
      activity, this leading to a decrease in the transplantability of bone marrow
      stromal tissue of old mice. Comparison of transplantations "old donor - young
      recipient" vs. "young donor - young recipient" demonstrated a decrease in the
      count of nuclear cells (1.8 times), size of bone capsule (2-fold), efficiency of
      MSC cloning (1.6 times), count of MSC per transplant (2.9 times), and count of
      osteogenic MSC per transplant (3.3 times). The concentrations of osteogenic MSC
      in transplants from young and old donors leveled in young recipients, that is,
      seemed to be regulated by the host. Serum concentrations of IL-10 and TNF-alpha
      in intact old mice were at least 2.9 and 2 times higher than in young animals,
      while the concentrations of almost all the rest studied cytokines (IL-2, IL-5, GM
      CSF, IFN-gamma, IL-4, IL-12) were lower. Presumably, the decrease in the content
      of bone marrow MSC and in transplantability of bone marrow stromal tissue in old
      mice were caused by exhaustion of the MSC pool as a result of age-specific
      chronic inflammation. These data indicated a close relationship between age
      specific changes in the stromal tissue and immune system.

PMID- 28744639
TI  - Expression of IFN-Inducible Genes with Antiviral Function OAS1 and MX1 in Health
      and under Conditions of Recurrent Herpes Simplex Infection.
AB  - We studied the expression of IFN-inducible genes OAS1 and Mx1 in lysates of
      peripheral blood mononuclear cells from patients suffering from recurrent Herpes
      simplex infections in comparison with healthy people. To induce the expression of
      the studied genes, blood mononuclears were incubated with recombinant IFN-alpha2b
      in concentrations of 1, 10, and 100 U/ml for 3 h and then the content of the
      studied transcripts was evaluated. Relative expression of OAS1 and Mx1 in
      patients with recurrent forms of Herpes simplex both during the acute stage and
      clinical remission did not differ significantly from that in healthy people after
      stimulation with IFN-alpha2b in a concentration of 1 U/ml and in higher
      concentrations (10 and 100 U/ml). It was concluded that intracellular signal
      transduction in IFN-alpha-activated cells in vitro was not disturbed in patients
      with recurrent forms of Herpes simplex infection. Thus, the reported phenomenon
      of IFN-signalling distortion by Herpes simplex virus proteins observed in
      experiments on model cell lines infected with Herpes simplex virus was not
      confirmed in our experiments on peripheral blood mononuclear cells from patients
      with Herpes simplex infection.

PMID- 28744640
TI  - Features of Lipoperoxidation, Antioxidant Defense, and Thiol/Disulfide System in
      the Pathogenesis of Infertility in Males, Carriers of Nonfunctional Variants of
      GSTT1 and GSTM1 Gene Polymorphisms.
AB  - Comparative analysis of the parameters of LPO, antioxidant defense (AOD), and the
      thiol/disulfide system was performed in fertile and infertile males of
      reproductive age carrying different genotypes of the glutathione system genes.
      Blood plasma, blood hemolysate, and ejaculate served as specimens for biochemical
      studies. A decrease in glutathione S-transferase activity was found in blood and
      ejaculate specimens from fertile and infertile carriers of nonfunctional
      GSTT1(0/0)/GSTM1(0/0) genotypes. In infertile carriers of nonfunctional
      GSTT1(0/0)/GSTM1(0/0) genotypes determining reduced glutathione S-transferase
      activity, a decrease in the concentration of low-molecular-weight cell
      antioxidant (reduced glutathione) and an increase in the concentration of
      secondary LPO products (TBA-reactive substances) were revealed. Identification of
      carriers the polymorphic GSTT1 and GSTM1 variants and analysis of activity of the
      thiol/disulfide system enzymes can be recommended for additional evaluation of
      the risk for reproductive dysfunction in men.

PMID- 28744641
TI  - Effect of Chronic Administration of Obestatin and Its Fragment FNAP-NH2 on
      Behavioral Activity and Nociceptive Threshold in Rats with Normal and Excess Body
      Weight.
AB  - The effects of chronic intranasal administration of 300 nmol/kg obestatin and its
      fragment FNAP-NH2 on behavioral activity and nociceptive threshold were examined
      in male Wistar rats with normal body weight or alimentary obesity. In normal
      rats, obestatin produced no effect on behavior and nociception, whereas FNAP-NH2
      fragment enhanced risk-taking behavior. Rats with excess body weight demonstrated
      less pronounced risk-taking behavior and elevated nociceptive threshold in
      comparison with normal animals, but these differences were abolished by chronic
      administration of FNAP-NH2.

PMID- 28744642
TI  - Effect of Noradrenergic Neurotoxin DSP-4 and Maprotiline on Heart Rate Spectral
      Components in Stressed and Resting Rats.
AB  - The effects of intraperitoneal DSP-4 (N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine, a noradrenergic neurotoxin) and maprotiline (an inhibitor of
      norepinephrine reuptake in synapses) on spectral components of heart rhythm
      variability were examined in outbred male and female rats treated with these
      agents in daily doses of 10 mg/kg for 3 days. At rest, DSP-4 elevated LF and VLF
      spectral components in male and female rats. Maprotiline elevated LF and VLF
      components in males at rest, increased HR and reduced all spectral components in
      resting females. Stress against the background of DSP-4 treatment sharply
      increased heart rate and reduced the powers of all spectral components
      (especially LF and VLF components). In maprotiline-treated rats, stress increased
      the powers of LF and VLF components. Thus, the central noradrenergic system
      participates in the formation of LF and VLF spectral components of heart rate
      variability at rest and especially during stressful stimulation, which can
      determine the phasic character of changes in the heart rate variability observed
      in stressed organism.

PMID- 28744643
TI  - Involvement of Autonomic Nervous System in Antiarrhythmic Effect of Intermittent
      Hypobaric Hypoxia.
AB  - We studied the involvement of the autonomic nervous system in the antiarrhythmic
      effect of intermittent hypobaric hypoxia modeled by daily placing the rats into
      an altitude chamber at 405 mm Hg (5000 m above sea level). The antiarrhythmic
      effect of hypoxia was observed on the model of acute coronary
      occlusion/reperfusion in vivo, but not during simulation of total
      ischemia/reperfusion of the isolated myocardium. Intravenous injection of
      ganglionic blocker hexamethonium (30 mg/kg) 15 min prior to in vivo coronary
      occlusion modeling abolished the antiarrhythmic effect of intermittent hypobaric
      hypoxia, which suggests that this effect is mediated via activation of the
      autonomic nervous system.

PMID- 28744644
TI  - Effect of GlcNAc-, Man- and Gal-Specific Lectins of the Cytosol, Nuclear
      Membrane, and Nuclear Matrix of Calf Brain Cortex on Proliferation Activity of
      Peripheral Blood Lymphocyte.
AB  - We studied the effect of GlcNAc-, Man-, and Gal-specific lectins isolated from
      cell cytosol, nuclear membrane, and nuclear matrix of calf brain cortex,
      lyophilized, and stored for 5 years on proliferation activity of human peripheral
      blood lymphocytes and on hemagglutination activity of trypsinized rabbit
      erythrocytes. Human peripheral blood lymphocytes treated lyophilized lectins
      demonstrated lower proliferation activity than lymphocytes treated with
      concanavalin A (positive control), but higher than control lymphocytes (incubated
      with saline). Lectins produced no effect on hemagglutination activity.

PMID- 28744645
TI  - Effect of Hypothermia on Kinetic Characteristics of Lactate Dehydrogenase in Rat
      Brain under Conditions of Global Ischemia and Reperfusion.
AB  - We studied activity and kinetic characteristics of lactate dehydrogenase (LDH) in
      rat brain under conditions of incomplete global ischemia followed by reperfusion
      against the background of mild hypothermia. It was found that hypothermia leads
      to a decrease in LDH activity in the ischemic brain; the maximum velocity of the
      enzyme-catalyzed activity decreased and Michaelis constant increased, due to
      which the efficiency of catalysis decreased to the level observed in control
      rats. Ischemia against the background of hypothermia was accompanied by a
      decrease in the inhibition constant and narrowing of effective pyruvate
      concentration range. Blood flow resumption in the ischemic brain against the
      background of mild hypothermia led to an increase in LDH activity, the maximum
      reaction velocity increased, and Michaelis constant decreased, which lead to a
      significant increase in the efficiency of catalysis. This was accompanied by an
      increase in enzyme inhibition constant and a shift of the optimum on the
      concentration curve towards lower pyruvate concentrations.

PMID- 28744646
TI  - Peptides Selected Using Phage Library Variants, Effectively Inhibit Trypanosoma
      cruzi Infection.
AB  - Four peptide sequences characterized by high content of hydrophobic, charged, and
      polar amino acids were obtained from 23 clones of M13 phage. Peptides P2 and P4
      exhibited highest binding affinity for immobilized trypomastigotes. The
      inhibitory effects of peptides seemed to be due to blockade of certain epitopes
      on T. cruzi surface proteins responsible for interactions with the respective
      receptors of host cells.

PMID- 28744647
TI  - Antioxidant and Antiamnestic Effects of Potassium Comenate and Comenic Acid under
      Conditions of Normobaric Hypoxia with Hypercapnia.
AB  - Potassium comenate and comenic acid exhibit manifest and virtually identical
      antioxidant activity under conditions of hypoxia with hypercapnia. The effects of
      these drugs on conditioned reflex training with positive reinforcement differ
      significantly. Potassium comenate promotes retention of the learning capacity and
      memory in hypoxic rats at the level of intact control, that is, exhibits a
      pronounced protective antiamnestic effect, while comenic acid only facilitates
      training of the conditioned reflex with positive reinforcement.

PMID- 28744648
TI  - Dynamics of the Development of Depressive-Like State in Rats Stressed by Chronic
      Exposure of Ultrasound of Variable Frequency.
AB  - We studied the effect of ultrasonic waves with a frequency of 20-45 kHz on
      behavioral reactions of rats after 7, 14 and 21 days of continuous exposure. A
      decrease in the number of social contacts in the social interest test was
      recorded in all groups, while lengthening of immobility time in Porsolt test was
      found only in the groups exposed to ultrasound for 2 and 3 weeks. Memory
      impairment in the new object recognition test was recorded only after 21 days of
      stressing. Chronic exposure to ultrasound of variable frequencies leads to the
      development of a depressive-like state in rats and the duration of exposure
      affects the specificity of the observed disorders. Different protocols of using
      of this model help to determine the stages of depressive-like condition in rats
      that can serve as a basis for the development of new methods of depressive
      disorders treatment.

PMID- 28744649
TI  - Electrophysiological Features of Single Store-Operated Calcium Channels in HEK S4
      Cell Line with Stable STIM1 Protein Knockdown.
AB  - An important role in intracellular calcium signaling is played by store-operated
      channels activated by STIM proteins, calcium sensors of the endoplasmic
      reticulum. In stable STIM1 knockdown HEK S4 cells, single channels activated by
      depletion of intracellular calcium stores were detected by cell-attached patch
      clamp technique and their electrophysiological parameters were described.
      Comparison of the properties of single channels in HEK293 and HEK S4 cells
      revealed no significant differences in their current-voltage curves, while
      regulation of store-operated calcium channels in these cell lines depended on the
      level of STIM1 expression. We can conclude that electrophysiological
      peculiarities of store-regulated calcium entry observed in different cells can be
      explained by differences in STIM1 expression.

PMID- 28744650
TI  - Role of NF-kappaB, PI3K, MAPK/ERK 1/2, and p38 in Erythropoietin Production by
      Bone Marrow Nuclears under Conditions of Immobilization Stress.
AB  - The involvement of the studied signal cascades in the regulation of
      erythropoietin production by bone marrow nuclears under conditions of
      immobilization stress depends on the type of the hemopoiesis-inducing
      microenvironment cells and the period of blood system reaction to stress
      exposure. Secretory activity of monocytes is regulated mainly by PI3K improving
      cell resistance to disturbances. The functional role of signal cascades involved
      in the production of erythropoietin by T cells is determined by the stage of the
      common adaptation syndrome.

PMID- 28744651
TI  - High Antimetastatic Activity of Platin Liposomal Form after Lyophilization and
      Storage.
AB  - Antimetastatic activity of Platin in lyophilized liposomes stored for 7 years
      after fabrication was evaluated. The main flaw of liposomes as vehicles for drug
      delivery to the tumors is their high affinity for the liver, which accumulates a
      great amount thereof. This property of liposomes can be used for adjuvant therapy
      of operable primary tumors metastasizing to the liver. It is shown on the model
      of mouse GA-1 tumor metastases in the liver that platinum(II) complex compound
      Platin in phosphatidylcholine-cholesterol liposomes, stored for 7 years after
      lyophilization, causes complete cure of 40% animals, while free Platin prolongs
      the lifespan of mice with tumors by only 31.7% vs. control (no treatment).

PMID- 28744652
TI  - Effects of Chitosan Derivative N-[(2-Hydroxy-3-Trimethylammonium)Propyl]Chloride
      on Anticoagulant Activity of Guinea Pig Plasma.
AB  - Intravenous injection of protamine sulfate or quarternized chitosan derivative to
      guinea pigs after injection of 70 aIIa U/kg non-fractionated heparin shortened
      plasma clotting time (shown by partial activated thromboplastin time, thrombin
      time, and prothrombin time). Intravenous injection of protamine sulfate or
      quarternized chitosan derivative to guinea pigs after injection of 1 mg/kg (100
      aXa U/kg) low-molecular-weight heparin (clexane) led to shortening of plasma
      clotting time in the ReaClot Heparin test and to prolongation of plasma
      amidolytic activity in the factor Xa chromogenic substrate test.

PMID- 28744653
TI  - Lipoxygenase Inhibitors Nordihydroguaiaretic Acid and Fungus Lecanicillum lecanii
      Extract Induce Death of Lymphoid Leukemia Cells.
AB  - We studied the effect of lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA)
      and fungus Lecanicillum lecanii extract on lymphatic leukemia P388 cells. The
      cells grown in the abdominal cavity of DBA2 mice for 7 days were transferred into
      a nutrient medium. The effect of lipoxygenase inhibitors was evaluated by changes
      in cell number, trypan blue staining, nucleus damage, and changes in cell
      distribution by DNA content after 22-h incubation. NDGA and fungus extract
      induced apoptotic death of lymphatic leukemia cells, which was seen from nucleus
      damage and reduced DNA content in cells. IC50 for NDGA and fungus extract was
      0.66 and 5.5 MUg/ml, respectively.

PMID- 28744654
TI  - Metabolic Restructuring in the Liver under Conditions of Endogenous Intoxication.
AB  - Significant metabolic alterations in the liver were observed in dogs with modeled
      acute peritonitis. These changes significantly impaired detoxification function
      of the liver, which was seen from the increase in the titer of toxic products in
      the early post-surgery period not only in the lymph, but also in the blood
      plasma. The key pathogenic mechanism leading to acute liver failure is
      destabilization of cell membrane resulting from LPO, phospholipase activity, and
      tissue hypoxia. Activation of LPO and increase in phospholipase activity in the
      liver tissues were observed within 12 h after peritonitis modeling.

PMID- 28744655
TI  - Whose Turn? Chromosome Research and the Study of the Human Genome.
AB  - A common account sees the human genome sequencing project of the 1990s as a
      "natural outgrowth" of the deciphering of the double helical structure of DNA in
      the 1950s. The essay aims to complicate this neat narrative by putting the
      spotlight on the field of human chromosome research that flourished at the same
      time as molecular biology. It suggests that we need to consider both endeavors -
      the human cytogeneticists who collected samples and looked down the microscope
      and the molecular biologists who probed the molecular mechanisms of gene function
      - to understand the rise of the human genome sequencing project and the current
      genomic practices. In particular, it proposes that what has often been described
      as the "molecularization" of cytogenetics could equally well be viewed as the
      turn of molecular biologists to human and medical genetics - a field long
      occupied by cytogeneticists. These considerations also have implications for the
      archives that are constructed for future historians and policy makers.

PMID- 28744656
TI  - ARMS2 A69S polymorphism is associated with the number of ranibizumab injections
      needed for exudative age-related macular degeneration in a pro re nata regimen
      during 4 years of follow-up.
AB  - PURPOSE: To investigate whether single-nucleotide polymorphisms (SNPs) known to
      be strongly associated with the development of age-related macular degeneration
      (AMD) have an influence on recurrence rate of choroidal neovascularization (CNV)
      activity during 4-year ranibizumab treatment for exudative AMD. METHODS: This
      prospective study included 103 treatment-naive patients (103 eyes) that received
      initially a loading dose of 3 monthly ranibizumab injections and thereafter, were
      treated according to an as-needed regimen for a 4-year follow-up period. Baseline
      values, visual outcome, and recurrence rate were examined. CFH Y402H and ARMS2
      A69S polymorphisms were determined and their association with lesion recurrence
      and visual outcome was analyzed using a one-way analysis of variance (ANOVA) with
      post hoc comparison tested by Fisher's LSD method. Multivariate linear regression
      analysis was then used to identify factors associated with recurrence rate.
      RESULTS: The cumulative total mean number of ranibizumab injections at the end of
      each year of the follow-up was 5.3 +/- 1.8, 9.2 +/- 2.9, 12.6 +/- 4.6, and 15.7
      +/- 6.1. There was great inter-patient variability. Nineteen eyes (18.5%) did not
      experience recurrence during the first year, and five (4.8%) still displayed
      inactive CNV after 4 years of follow-up. No significant association was found
      between the number of injections and mean best corrected visual acuity (BCVA)
      change or final BCVA at the end of the study period. Genotypes had no influence
      on baseline characteristics or visual outcome but a significant association was
      found between the A69S polymorphism and the number of injections needed by the
      patients. Homozygous for the T risk allele required more retreatments over the 48
      month follow-up. CONCLUSIONS: The ARMS2 A69S polymorphism was associated with CNV
      recurrence rate in our patient cohort. Prediction of a greater risk of recurrence
      could help to design more appropriate follow-up treatment strategies for patients
      with neovascular AMD.

PMID- 28744657
TI  - Ranibizumab versus dexamethasone implant for central retinal vein occlusion: the
      Ranidex study.

PMID- 28744658
TI  - Characteristics of retinal vessels in surgically closed macular hole: an optical
      coherence tomography angiography study.
AB  - PURPOSE: The purpose of our study was to investigate characteristics of retinal
      vessels in eyes with surgically closed macular holes (MH). METHODS: We included
      patients who underwent surgery for idiopathic MH and a follow-up examination
      using optical coherence tomography angiography (OCTA). The area of the foveal
      avascular zone (FAZ) and retinal vascular densities of the superficial capillary
      plexus (SCP) and deep capillary plexus (DCP) were calculated on the postoperative
      OCTA images and compared with those of age-matched normal controls. RESULTS:
      Twenty-eight patients with MH and 28 controls were included. Mean postoperative
      FAZ areas of SCP and DCP (0.317 +/- 0.129 mm2 and 0.500 +/- 0.174 mm2) were
      smaller than those of normal controls (0.406 +/- 0.131 mm2 and 0.687 +/- 0.147
      mm2) (P = 0.013 and P < 0.001, respectively). Retinal vascular densities of SCP
      and DCP in the MH group (32.23 +/- 1.45% and 31.85 +/- 1.28%) were lower than
      those of the control group (33.26 +/- 1.71% and 33.18 +/- 1.89%) (P = 0.019 and P
      = 0.003, respectively). The retinal vascular densities of SCP and DCP were
      associated with postoperative mean ganglion cell-inner plexiform layer (GC-IPL)
      thickness (P = 0.033 and P = 0.035, respectively). The vascular densities were
      horizontally asymmetric and related to asymmetric distribution of GC-IPL
      thickness in the MH group. CONCLUSIONS: Surgically closed MH eyes had remodeled
      retinal vascular patterns, which were related to morphologic changes in the inner
      retinal layer. The healing process after MH surgery may be involved in asymmetric
      change in anatomy and hemodynamics of the inner retina.

PMID- 28744659
TI  - Multifactorial assessment is essential to maximize the likelihood of good
      outcomes after endoscopic dacryocystorhinostomy.

PMID- 28744660
TI  - Assessment of laryngopharyngeal reflux and the shape of the Eustachian tube
      should be considered in chronic rhinosinusitis with nasal polyps and chronic
      otitis media.

PMID- 28744661
TI  - Commentary on "Clinical and audiologic characteristics of patients with
      sensorineural tinnitus and its association with psychological aspects: an
      analytic retrospective study".

PMID- 28744662
TI  - Letter to editor: Current and future techniques for human papilloma virus (HPV)
      testing in oropharyngeal squamous cell carcinoma.

PMID- 28744663
TI  - Serotypes of Streptococcus pneumoniae in Egyptian children: are they covered by
      pneumococcal conjugate vaccines?
AB  - In Egypt, pneumococcal vaccines have not yet been introduced as being compulsory.
      Identification of the circulating serotypes in Egypt is mandatory to determine
      whether or not the pneumococcal vaccines will be beneficial. The current study
      aims to identify the serotypes, vaccine coverage, and antimicrobial resistance of
      Streptococcus pneumoniae colonizing the nasopharynx of Egyptian children younger
      than 5 years old. The study was conducted in two successive winter seasons
      (December 2012-February 2013 and December 2013-February 2014). Two hundred
      children were enrolled, aged from 6 months to 5 years, excluding those with
      fever, signs of infection, history of antibiotic intake, and hospitalization in
      the preceding month. Nasopharyngeal (NP) secretions were collected, subjected to
      culture, and underwent antibiotic susceptibility testing if positive for
      pneumococci. Real-time polymerase chain reaction (PCR) and serotyping by
      sequential multiplex PCR for positive cases were included as well. Streptococcus
      pneumoniae was isolated from 62 subjects. All isolates were sensitive to
      vancomycin and levofloxacin, but the majority showed resistance to multiple
      antibiotics. PCR was positive for pneumococci in 113 subjects (56.5%). The most
      commonly detected serotypes (st) were 6A6B6C (n = 21, 20.8%), 19F (n = 19,
      18.8%), 1 (n = 11, 10.9%), 34 (n = 8, 7.9%), and 19A (n = 6, 5.9%). The
      theoretical coverage of the PCV13 vaccine for the detected serotypes was 72.4%,
      while that of PCV10 was 65.5%. Based on these percentages, we recommend including
      pneumococcal conjugate vaccines in the Egyptian national vaccination program.

PMID- 28744664
TI  - Evaluation of the Carba NP test for carbapenemase detection in
      Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp., and its practical
      use in the routine work of a national reference laboratory for susceptibility
      testing.
AB  - The aim of this study was to evaluate the Carba NP test (and CarbAcineto) for the
      detection of carbapenemases in Enterobacteriaceae, Pseudomonas spp. and
      Acinetobacter spp., and to assess its usefulness in the routine work of the
      National Reference Centre for Susceptibility Testing (NRCST) in Poland. The
      evaluation of the Carba NP/CarbAcineto tests was carried out on a group of 81
      Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp. isolates producing
      KPC-, NDM-, VIM-, IMP- or OXA-48, -23, -24/40, -58-type carbapenemases, and on 26
      carbapenemase-negative strains cultivated on a broad panel of microbiological
      media. Subsequently, the performance of the Carba NP/CarbAcineto tests was
      assessed on 1282 isolates of Enterobacteriaceae, Pseudomonas spp. and
      Acinetobacter spp. from Polish hospitals, submitted to the NRCST during a 9-month
      period in 2014. The Carba NP/CarbAcineto results were compared with other
      phenotypic tests and/or polymerase chain reaction (PCR). The impact of the media
      on the results of the Carba NP/CarbAcineto tests was observed, with the Columbia
      blood agar yielding the highest sensitivity and clarity of the results.
      Furthermore, the Carba NP/CarbAcineto tests were included in the NRCST routine
      procedure for carbapenemase identification. The sensitivity and specificity of
      the Carba NP test were 95.8% and 93.3%, respectively, for Enterobacteriaceae, and
      97.5% and 99.0%, respectively, for Pseudomonas spp. The sensitivity of the
      CarbAcineto test for Acinetobacter spp. was 88.9%. This study confirmed the
      usefulness of the Carba NP/CarbAcineto tests for the rapid detection of various
      types of carbapenemases.

PMID- 28744665
TI  - Perceived discrimination and health-related quality-of-life: gender differences
      among older African Americans.
AB  - PURPOSE: Emerging data suggest that African-American women may fare worse than
      African-American men in health-related quality-of-life (HRQOL). Perceived
      discrimination is an important contributor to poor health overall among African
      Americans, but few studies examined the intersecting effects of perceived
      discrimination and gender in explaining HRQOL disparities. We investigated gender
      differences in HRQOL and tested whether perceived discrimination accounted for
      these differences. METHODS: We examined data from the Chicago Health and Aging
      Project in which 5652 African-American adults aged 65 and older completed
      structured questionnaires about demographic and socioeconomic characteristics,
      HRQOL, perceived discrimination, and health-related variables. Logistic
      regression models were used to identify associations between perceived
      discrimination and gender differences in poor HRQOL outcomes (defined as 14+
      unhealthy days in overall, physical, or mental health over the past 30 days) when
      controlling for the other variables. RESULTS: More women reported poor overall
      HRQOL than men (24 vs. 16% respectively). Higher perceived discrimination was
      significantly associated with worse overall HRQOL (OR 1.11; 95% CI 1.08, 1.15),
      with stronger effects for women in overall and mental HRQOL. These gender
      disparities remained significant until controlling for potentially confounding
      variables. Perceived discrimination did not account for gender differences in
      poor physical HRQOL. CONCLUSIONS: Perceived discrimination is associated with
      poor HRQOL in older African Americans, with this association appearing stronger
      in women than men for mental HRQOL. These findings warrant further investigation
      of effects of perceived discrimination in gender disparities in overall health,
      and such research can inform and guide efforts for reducing these disparities.

PMID- 28744666
TI  - Lessons for Patient Education Around Long-Acting Injectable PrEP: Findings from a
      Mixed-Method Study of Phase II Trial Participants.
AB  - This study aimed to identify patients' physical and psychosocial experiences of
      an investigational long-acting injectable PrEP product to aid in the development
      of patient and provider education materials. Twenty-eight participants of a Phase
      2 safety, tolerability, and acceptability study of long-acting integrase
      inhibitor cabotegravir (CAB-LA) were interviewed on their physical and
      psychosocial experiences of the injections. Five themes emerged through a
      framework analysis on these interview transcripts: (1) injection-related pain is
      highly variable across individuals; (2) pain is more impactful after the
      injections than during; (3) patient anxiety is critical, but does not determine
      the experience of injections and decreases over time; (4) intimacy and
      awkwardness of gluteal injections impacts patients' experiences; (5) patient
      education and care strategies can mitigate the above factors. These findings can
      inform further sociobehavioral research within Phase 3 efficacy trials of CAB-LA,
      as well as patient education and provider guidance for future injectable PrEP
      products.

PMID- 28744667
TI  - Exposure-response relationship of ramucirumab in patients with advanced second
      line colorectal cancer: exploratory analysis of the RAISE trial.
AB  - PURPOSE: To characterize ramucirumab exposure-response relationships for efficacy
      and safety in patients with metastatic colorectal cancer (mCRC) using data from
      the RAISE study. METHODS: Sparse pharmacokinetic samples were collected; a
      population pharmacokinetic analysis was conducted. Univariate and multivariate
      Cox proportional hazards models analyzed the relationship between predicted
      ramucirumab minimum trough concentration at steady state (C min,ss) and survival.
      Kaplan-Meier analysis was used to evaluate survival from patients in the
      ramucirumab plus folinic acid, 5-fluorouracil, and irinotecan (FOLFIRI) treatment
      arm stratified by C min,ss quartiles (Q). An ordered categorical model analyzed
      the relationship between C min,ss and safety outcomes. RESULTS: Pharmacokinetic
      samples from 906 patients were included in exposure-efficacy analyses; samples
      from 905 patients were included in exposure-safety analyses. A significant
      association was identified between C min,ss and overall survival (OS) and
      progression-free survival (PFS) (p < 0.0001 for both). This association remained
      significant after adjusting for baseline factors associated with OS or PFS (p <
      0.0001 for both). Median OS was 11.5, 12.9, 16.4, and 16.7, and 12.4 months for
      ramucirumab C min,ss Q1, Q2, Q3, Q4, and placebo group, respectively. Median PFS
      was 5.4, 4.6, 6.8, 8.5, and 5.2 months for ramucirumab C min,ss Q1, Q2, Q3, Q4,
      and placebo group, respectively. The risk of Grade >=3 neutropenia was associated
      with an increase in ramucirumab exposure. CONCLUSIONS: Exploratory exposure
      response analyses suggested a positive relationship between efficacy and
      ramucirumab exposure with manageable toxicities in patients from the RAISE study
      with mCRC over the ranges of exposures achieved by a dose of 8 mg/kg every 2
      weeks in combination with FOLFIRI.

PMID- 28744668
TI  - Single-port thoracoscopic lung wedge resection using the Endo GIA Radial Reload.
AB  - The GIA Radial Reload is a surgical stapler with a curved cut line that is
      perpendicular to the direction of instrument insertion. We used the GIA Radial
      Reload in three cases of single-port thoracoscopic lung wedge resection. The
      operations were performed through a 3.0-4.5-cm incision. For the first stapler,
      we selected the GIA Radial Reload. The orientation of this device's cut line
      enabled us to easily cut the lung behind the lesion during single-port
      thoracoscopic surgery.

PMID- 28744669
TI  - Adsorption of ammonium from simulated wastewater by montmorillonite nanoclay and
      natural vermiculite: experimental study and simulation.
AB  - In this research, montmorillonite nanoclay (MNC) and vermiculite were used to
      adsorb ammonium (NH4+) from simulated wastewater. The effect of organic acids,
      cations, and anions on adsorption of NH4+ was also studied using batch
      experiments. The presence of organic acids significantly decreased the NH4+
      adsorption using both adsorbents and the reduction followed the order of citric
      acid > malic acid > oxalic acid. The presence of cations in wastewater could
      decrease the adsorption of NH4+ and the ion exchange selectivity on the MNC and
      vermiculite followed the orders Mg > Ca >= K > Na and Mg > > Ca > Na > K,
      respectively. Adsorption of NH4+ by adsorbents in the presence of sulfate (SO4)
      was higher than those in the presence of phosphate (PO4) and chloride (Cl)
      anions. Results indicated that MNC and vermiculite had good potential for NH4+
      removal depending on adsorbent dosage, pH, contact time, and initial NH4+
      concentration. The effect of pH on removal of NH4+ indicated that MNC would be
      more appropriate as the adsorbent than vermiculite at low pH values. Kinetic
      analysis demonstrated that the rate-controlling step adsorption for NH4+ by MNC
      and vermiculite was heterogeneous chemisorption and followed the pseudo-second
      order model. The desorption experiments indicated that the adsorption of NH4+ by
      adsorbents was not fully reversible, and the total recovery of adsorbed NH4+ for
      MNC and vermiculite varied in the range of 72 to 94.6% and 11.5 to 45.7%,
      respectively. Cation exchange model (CEM) in PHREEQC program was used to simulate
      NH4+ adsorption. Agreement between measured and simulated data suggested that CEM
      was favored in simulating adsorption of NH4+ by clay minerals. The results
      indicated that MNC and vermiculite have good performance as economic and nature
      friendly adsorbents that can ameliorate the water and environment quality.

PMID- 28744670
TI  - RNA-binding protein HuR enhances mineralocorticoid signaling in renal KC3AC1
      cells under hypotonicity.
AB  - Mineralocorticoid receptor (MR) mediates the sodium-retaining action of
      aldosterone in the distal nephron. Herein, we decipher mechanisms by which
      hypotonicity increases MR expression in renal principal cells. We identify HuR
      (human antigen R), an mRNA-stabilizing protein, as an important
      posttranscriptional regulator of MR expression. Hypotonicity triggers a rapid and
      reversible nuclear export of HuR in renal KC3AC1 cells, as quantified by high
      throughput microscopy. We also identify a key hairpin motif in the 3'
      untranslated region of MR transcript, pivotal for the interaction with HuR and
      its stabilizing function. Next, we show that hypotonicity increases MR
      recruitment onto Sgk1 promoter, a well-known MR target gene, thereby enhancing
      aldosterone responsiveness. Our data shed new light on the crucial role of HuR as
      a stabilizing factor for the MR transcript and provide evidence for a short
      autoregulatory loop in which expression of a nuclear receptor transcriptionally
      regulating water and sodium balance is controlled by osmotic tone.

PMID- 28744672
TI  - Unresolved Issues in Thrombectomy.
AB  - PURPOSE OF REVIEW: Trials demonstrating marked benefit of mechanical thrombectomy
      (MT) for acute stroke caused by large vessel occlusion (LVO) in the anterior
      circulation have been the most significant advance in acute ischemic stroke in
      the past 20 years. However, despite this marked advance, there are still many
      hurdles to improving access to thrombectomy worldwide. Additionally, despite
      these advances, a substantial portion of patients with LVO still are left
      disabled. RECENT FINDINGS: The major randomized trials focused on patients within
      6 h from symptom onset, with occlusion of the ICA or proximal MCA, small amount
      of permanently damaged brain, and a moderate to large clinical deficit. We will
      explore the role of thrombectomy outside of these areas, but also explore larger
      issues as they pertain to re-organization of stroke systems of care to improve
      access to this remarkable therapy. Now that we have proven, without a shadow of
      doubt, that rapid revascularization with mechanical thrombectomy improves
      outcomes in LVO stroke, we must reorganize our systems of care to improve access
      and assess the role for MT outside of the patients who meet trial criteria.

PMID- 28744673
TI  - Utilization of MR angiography in perfusion imaging for identifying arterial input
      function.
AB  - OBJECTIVE: This research utilizes magnetic resonance angiography (MRA) to
      identify arterial locations during the parametric evaluation of concentration
      time curves (CTCs), and to prevent shape distortions in arterial input function
      (AIF). MATERIALS AND METHODS: We carried out cluster analysis with the CTC
      parameters of voxels located within and around the middle cerebral artery (MCA).
      Through MRA, we located voxels that meet the AIF criteria and those with
      distorted CTCs. To minimize partial volume effect, we re-scaled the time integral
      of CTCs by the time integral of venous output function (VOF). We calculated the
      steady-state value to area under curve ratio (SS:AUC) of VOF and used it as a
      reference in selecting AIF. CTCs close to this reference value (selected AIF) and
      those far from it were used (eliminated AIF) to compute cerebral blood flow
      (CBF). RESULTS: Eliminated AIFs were found to be either on or anterior to MCA,
      whereas selected AIFs were located superior, inferior, posterior, or anterior to
      MCA. If the SS:AUC of AIF was far from the reference value, CBF was either under-
      or over-estimated by a maximum of 41.1 +/- 14.3 and 36.6 +/- 19.2%, respectively.
      CONCLUSION: MRA enables excluding voxels on the MCA during cluster analysis, and
      avoiding the risk of shape distortions.

PMID- 28744674
TI  - Liquid droplets on a free-standing glassy membrane: Deformation through the glass
      transition.
AB  - In this study, micro-droplets are placed on thin, glassy, free-standing films
      where the Laplace pressure of the droplet deforms the free-standing film,
      creating a bulge. The film's tension is modulated by changing temperature
      continuously from well below the glass transition into the melt state of the
      film. The contact angle of the liquid droplet with the planar film as well as the
      angle of the bulge with the film are measured and found to be consistent with the
      contact angles predicted by a force balance at the contact line.

PMID- 28744671
TI  - Mechanisms regulating immune surveillance of cellular stress in cancer.
AB  - The purpose of this review is to explore immune-mediated mechanisms of stress
      surveillance in cancer, with particular emphasis on the idea that all cancers
      have classical hallmarks (Hanahan and Weinberg in Cell 100:57-70, 67; Cell
      144:646-674, 68) that could be interrelated. We postulate that hallmarks of
      cancer associated with cellular stress pathways (Luo et al. in Cell 136:823-837,
      101) including oxidative stress, proteotoxic stress, mitotic stress, DNA damage,
      and metabolic stress could define and modulate the inflammatory component of
      cancer. As such, the overarching goal of this review is to define the types of
      cellular stress that cancer cells undergo, and then to explore mechanisms by
      which immune cells recognize, respond to, and are affected by each stress
      response.

PMID- 28744675
TI  - Potentially inappropriate medication at hospital admission in patients with
      palliative care needs.
AB  - Background Potentially inappropriate medications (PIMs) are common in older
      patients with polypharmacy, and are related to negative clinical results. Little
      information is available on the characteristics and consequences of PIMs in
      patients with advanced chronic conditions and palliative care needs. Objective To
      evaluate, for this population: (i) the prevalence of PIMs; (ii) the possible risk
      factors associated with its onset; and (iii) the related clinical consequences.
      Setting Acute-hospital care Geriatric Unit (AGU) in County of Osona, Spain.
      Method Ten-month prospective cross-sectional study. Patients with palliative care
      needs were identified according to the NECPAL CCOMS-ICO(r) test. Upon hospital
      admission, a multidisciplinary team consisting of a pharmacist and two AGU
      physicians determined the PIMs of the routine chronic medication of the patients.
      Sociodemographic and pharmacological data were collected with the objective of
      determining possible risk factors related to the existence of PIMs. Main outcome
      measure Prevalence and type of PIMs according to STOPP version 2 and MAI criteria
      at the time of hospital admission. Furthermore, days of hospital admission,
      destination at hospital discharge and survival analysis at 12 months related to
      PIMs were evaluated. Results Two hundred thirty-five patients (mean age 86.80, SD
      5.37; 65.50% women) were recruited. According to the STOPP criteria, 88.50% of
      patients had >=1 criterion (mainly 'indication of medication', followed by those
      that affect the nervous system and psychotropic drugs and risk drugs in people
      suffering from falls), and according to the MAI tool, 97.40% of the patients had
      some criterion related to inappropriate medication (mainly, duration of therapy).
      The following conditions were identified as risk factors for the existence of
      PIMs: insomnia, anxiety-depressive disorder, falls, pain, excessive polypharmacy
      and therapeutic complexity. There were no differences among patients in days of
      hospital stay, discharge's destination or survival at 12 months, regardless of
      the tool used. Conclusion The presence of PIMs is high in patients requiring
      palliative care. Some potentially modifiable risk factors such as the
      pharmacological ones are associated with a greater presence of inappropriate
      medication. The presence of PIMs does not affect this population in terms of
      mortality.

PMID- 28744676
TI  - Anti-oviposition activities of used sock media against a dengue vector: prospects
      of eco-friendly control and solutions to pollution.
AB  - Yearly, huge amounts of sock refuse are discarded into the environment. Socks
      contain many molecules, and worn ones, which are rich in smell-causing bacteria,
      have a strong influence on animals' behaviors. But the impacts of sock odor on
      the oviposition behavior of dengue vectors are unknown. We assessed whether Aedes
      albopictus changes its oviposition activity in response to the presence of used
      socks extract (USEx) in potential breeding grounds, using choice and no-choice
      bioassays (NCB). When furnished even chances to oviposit in two sites holding
      USEx and two others containing water (control), Ae. albopictus deposited
      significantly less eggs in USEx than in water sites. A similar pattern of
      oviposition preference was also observed when there were more oviposition options
      in water. When there were greater oviposition opportunities in USEx sites, Ae.
      albopictus oviposited preferentially in water. Females laid significantly more
      eggs during the NCB involving water than USEx. Also, significantly more mature
      eggs were retained by females in the NCB with USEx than in that with water. These
      observations strongly suggest the presence of molecules with either repellent or
      deterrent activities against Ae. albopictus females and provide an impetus to
      advocate the integration of used socks in dengue control programs. Such
      applications could be a realistic end-of-life recourse to reroute this waste from
      landfills.

PMID- 28744677
TI  - Light absorption by water-soluble organic carbon in atmospheric fine particles in
      the central Tibetan Plateau.
AB  - Brown carbon (BrC) has recently received much attention because of its light
      absorption features. The chemical compositions, optical properties, and sources
      of fine aerosol at a high-elevation mountain observatory (4730 m a.s.l.) in the
      central Tibetan Plateau were measured between 31 May and 1 July 2015. A low flow
      rate sampler was used to collect 24-h average fine particulate matter (PM2.5)
      filter samples. Water-soluble ions, organic carbon (OC), elemental carbon, water
      soluble organic carbon (WSOC), and light absorption by water-soluble BrC were
      determined for 26 filter samples. The mean (+/- 1sigma) OC and WSOC
      concentrations were 0.76 +/- 0.43 and 0.39 +/- 0.15 MUgC/m3, respectively, and
      the mean WSOC/OC mass ratio was 0.59 +/- 0.22. The OC and WSOC concentrations
      were relatively higher (0.59-1.80 and 0.33-0.83 MUgC/m3, respectively) during the
      pre-monsoon period (2-13 June) and were relatively lower (0.27-0.77 and 0.12-0.50
      MUgC/m3, respectively) during the monsoon period (14 June to 1 July), probably
      because of wet scavenging of aerosols during long-range transport and the
      presence of cleaner marine air masses during the monsoon period. The absorption
      spectra of PM2.5 water extracts smoothly increase from visible range to
      ultraviolet range. The absorption Angstrom exponent, which describes the
      wavelength dependence of water-soluble BrC, was 2.74-10.61 (mean 6.19 +/- 1.70),
      and its value was similar in the pre-monsoon period (6.57 +/- 0.56) to that in
      the monsoon period (5.91 +/- 2.14). The water-soluble BrC mass absorption
      efficiency, 0.38 +/- 0.16 m2/(g C), was much lower than those observed in most
      urban areas but similar to those in other remote sites. Absorption coefficient at
      365 nm, typically used as a proxy for water-soluble BrC, correlated well with the
      WSOC concentration (R 2  = 0.57), K+ concentration (R 2  = 0.75), and organic
      aerosol biomass burning markers characterized by an Aerodyne aerosol mass
      spectrometer (C2H4O2+ + C3H5O2+, R 2  = 0.60). It can be inferred that biomass
      burning was an important source of water-soluble BrC in the study area combined
      with air mass back trajectory analysis using the NOAA HYSPLIT as well as MODIS
      data of fire dots and aerosol optical depths. The water-soluble BrC to BC light
      absorption (at 365 nm) coefficient ratios were 9-27%.

PMID- 28744678
TI  - Variation of preserving organic matter bound in interlayer of montmorillonite
      induced by microbial metabolic process.
AB  - This paper aimed to investigate the variation of preserving organic matter bound
      in the interlayer space of montmorillonite (Mt) induced by a microbe metabolic
      process. We selected Bacillus pumilus as the common soil native bacteria. The
      alteration of d 001 value, functional group, and C,N organic matter contents
      caused by bacteria were analyzed by XRD, FTIR, and elementary analyzer,
      respectively. XRD results showed that the d 001 value of montmorillonite
      increased with the concentration decreasing and decreased with the culture time
      increasing after interacting with bacteria indicating the interlayer space of
      montmorillonite was connected with the organic matter. The findings of long-term
      interaction by resetting culture conditions implied that the montmorillonite
      buffered the organic matter when the nutrition was enough and released again when
      the nutrition was lacking. The results of the elementary analyzer declared the
      content of organic matter was according to the d 001 value of montmorillonite and
      N organic matter which played a major impact. FTIR results confirmed that the Si
      O stretching vibrations of Mt were affected by the functional group of organic
      matter. Our results showed that the montmorillonite under the influence of soil
      bacteria has a strong buffering capacity for preserving organic matter into the
      interlayer space in a short-term. It might provide critical implications for
      understanding the evolution process and the preservation of fertilization which
      was in the over-fertilization or less-fertilization conditions on farmland.

PMID- 28744679
TI  - Environmental monitoring of water resources around a municipal landfill of the
      Rio Grande do Sul state, Brazil.
AB  - In Brazil, landfills are commonly used as a method for the final disposal of
      waste that is compliant with the legislation. This technique, however, presents a
      risk to surface water and groundwater resources, owing to the leakage of metals,
      anions, and organic compounds. The geochemical monitoring of water resources is
      therefore extremely important, since the leachate can compromise the quality and
      use of surface water and groundwater close to landfills. In this paper, the
      results of analyses of metals, anions, ammonia, and physicochemical parameters
      were used to identify possible contamination of surface water and groundwater in
      a landfill area. A statistical multivariate approach was used. The values found
      for alkali metals, nitrate, and chloride indicate contamination in the regional
      groundwater and, moreover, surface waters also show variation when compared to
      the other background points, mainly for ammonia. Thus, the results of this study
      evidence the landfill leachate influence on the quality of groundwater and
      surface water in the study area.

PMID- 28744680
TI  - The effect of corn distiller's dried grains with solubles (DDGS) fortified with
      enzyme on growth performance of broiler.
AB  - The objective of the current study was to investigate the effect of corn
      distiller's dried grains with solubles (DDGS) and enzyme supplementation on
      growth performance and carcass yield in broiler chickens. The experiment was a 5
      * 3 factorial design with 450 broiler chickens and with diets containing five
      levels of DDGS (0, 6, 12, 18, and 24%) and three levels of the enzymes (no
      supplementation, Rovabio(r) enzyme, and Tomoko(r) enzyme). Five pens with six
      chicks were fed an experimental diet from 0 to 35 days of age. Diets containing
      12, 18, and 24% DDGS decreased performance (P < 0.05) at the start of the trial
      at 0-10 days. Inclusion of enzyme during 0-10 days improved body weight gain
      (BWG) and European production efficiency factor (EPEF) (P < 0.05). During the
      grower (11-24 days) and finisher (25-35 days) periods, chickens which had
      received 0, 6, or 12% DDGS converted feed to body weight more efficiently (P <
      0.05). Enzyme supplementation improved feed conversion ratio (FCR) for the
      periods (11-24 and 25-35 days, respectively) (P < 0.05). The cumulative
      performance results (0 to 35 days of age) showed that Tomoko enzyme improved FCR
      as compared to no enzyme while Rovabio was intermediate (P < 0.05). Chickens
      which had received 0, 6, or 12% had better FCR (P < 0.05) compared to 18 or 24%
      DDGS. Chick's performance was depressed at early age when the diet contained 12%
      DDGS but later, they were able to tolerate higher levels of DDGS. The study
      indicate that a maximum level of DDGS to use in the starter diets is 6% and it
      could be increased in the grower and finisher period to 12% and enzyme
      supplementation to diets containing DDGS can improve FCR and growth performance
      in broilers.

PMID- 28744681
TI  - An analysis of variable dissolution rates of sacrificial zinc anodes: a case
      study of the Hamble estuary, UK.
AB  - Sacrificial anodes are intrinsic to the protection of boats and marine structures
      by preventing the corrosion of metals higher up the galvanic scale through their
      preferential breakdown. The dissolution of anodes directly inputs component
      metals into local receiving waters, with variable rates of dissolution evident in
      coastal and estuarine environments. With recent changes to the Environmental
      Quality Standard (EQS), the load for zinc in estuaries such as the Hamble, UK,
      which has a large amount of recreational craft, now exceeds the zinc standard of
      7.9 MUg/l. A survey of boat owners determined corrosion rates and estimated zinc
      loading at between 6.95 and 7.11 t/year. The research confirms the variable anode
      corrosion within the Hamble and highlighted a lack of awareness of anode
      technology among boat owners. Monitoring and investigation discounted metal
      structures and subterranean power cables as being responsible for these
      variations but instead linked accelerated dissolution to marina power supplies
      and estuarine salinity variations.

PMID- 28744682
TI  - Environmental risk assessment of blight-resistant potato: use of a crop model to
      quantify nitrogen cycling at scales of the field and cropping system.
AB  - Environmental risk assessment of GM crops in Europe proceeds by step-wise
      estimation of effect, first in the plant, then the field plot (e.g. 10-100 m-2),
      field (1000-10,000 m-2) and lastly in the environment in which the crop would be
      grown (100-10,000 km2). Processes that operate at large scales, such as cycling
      of carbon (C) and nitrogen (N), are difficult to predict from plot scales. Here,
      a procedure is illustrated in which plot scale data on yield (offtake) and N
      inputs for blight resistant (both GM and non-GM) and blight-susceptible potato
      are upscaled by a model of crop resource use to give a set of indicators and
      metrics defining N uptake and release in realistic crop sequences. The greatest
      potential damage to environment is due to loss of N from the field after potato
      harvest, mainly because of the large quantity of mineral and plant matter, high
      in N, that may die or be left in the field. Blight infection intensifies this
      loss, since less fertiliser N is taken up by plants and more (as a proportion of
      plant mass) is returned to the soil. In a simulation based on actual crop
      sequences, N returns at harvest of potato were raised from 100 kg ha-1 in
      resistant to 150 kg ha-1 in susceptible varieties subject to a 40% yield loss.
      Based on estimates that blight-resistant types would require ~20% of the
      fungicide applied to susceptible types, introduction of resistant types into a
      realistic 6-year cropping sequence would reduce overall fungicide use to between
      72 and 54% depending on the inputs to other crops in the sequence.

PMID- 28744683
TI  - Sources and toxicities of phenolic polychlorinated biphenyls (OH-PCBs).
AB  - Polychlorinated biphenyls (PCBs), a group of 209 congeners that differ in the
      number and position of chlorines on the biphenyl ring, are anthropogenic
      chemicals that belong to the persistent organic pollutants (POPs). For many
      years, PCBs have been a topic of interest because of their biomagnification in
      the food chain and their environmental persistence. PCBs with fewer chlorine
      atoms, however, are less persistent and more susceptible to metabolic attack,
      giving rise to chemicals characterized by the addition of one or more hydroxyl
      groups to the chlorinated biphenyl skeleton, collectively known as hydroxylated
      PCBs (OH-PCBs). In animals and plants, this biotransformation of PCBs to OH-PCBs
      is primarily carried out by cytochrome P-450-dependent monooxygenases. One of the
      reasons for infrequent detection of lower chlorinated PCBs in serum and other
      biological matrices is their shorter half-lives, and their metabolic
      transformation, resulting in OH-PCBs or their conjugates, such as sulfates and
      glucuronides, or macromolecule adducts. Recent biomonitoring studies have
      reported the presence of OH-PCBs in human serum. The occurrence of OH-PCBs, the
      size of this group (there are 837 mono-hydroxyl PCBs alone), and their wide
      spectra of physical characteristics (pKa's and log P's ranging over 5 to 6 orders
      of magnitude) give rise to a multiplicity of biological effects. Among those are
      bioactivation to electrophilic metabolites that can form covalent adducts with
      DNA and other macromolecules, interference with hormonal signaling, inhibition of
      enzymes that regulate cellular concentrations of active hormones, and
      interference with the transport of hormones. This new information creates an
      urgent need for a new perspective on these often overlooked metabolites.

PMID- 28744684
TI  - The chemistry and toxicity of discharge waters from copper mine tailing
      impoundment in the valley of the Apuseni Mountains in Romania.
AB  - Copper mining generates large quantities of waste, tailings, and acid outflows
      causing long-term environmental impacts and potential threats to human health.
      Valea Sesei is the largest tailing impoundment in Romania, created by flooding
      the valley (known as Valea Sesei) of the Metalliferous Mountains (a division of
      the Apuseni Mountains) with copper mining waste. The present study (i) estimated
      the total volume of tailings in this area; (ii) screened the concentration of 65
      elements (rare earth and platinum group elements, alkali metals and alkali earth
      metals, transition and post-transition metals and metalloids) and cyanide
      concentrations in wastewater samples collected from tailing impoundment; (iii)
      evaluated the toxicity of these water samples using five in vitro bioassays
      employing human cells isolated from healthy donors and a short-term (1 h)
      exposure model. The sampled waters were highly acidic (pH 2.1-4.9) and had high
      electrical conductivity (2.80-15.61 mS cm-1). No cyanides were detected in any
      sample. Water samples collected from the stream (AMD) inflowing to the tailing
      impoundment were characterized by the greatest concentrations of alkali metals,
      alkaline earth metals, transition and post-transition metals, metalloids, rare
      earth elements, and noble metal group. At other sites, the elemental
      concentrations were lower but remained high enough to pose a relevant risk. The
      greatest magnitude of in vitro toxic effects was induced by AMD. Observed
      alterations included redox imbalance in human neutrophils followed by lipid
      peroxidation and decreased cell survival, significant aggregation of red blood
      cells, and increased prothrombin time. The study highlights that Valea Sesei is a
      large sink for toxic elements, posing environmental and health risks, and
      requiring action to prevent further release of chemicals and to initiate
      restoration of the area.

PMID- 28744685
TI  - Hydrochemical evaluation and identification of geochemical processes in the
      shallow and deep wells in the Ramganga Sub-Basin, India.
AB  - Groundwater samples were collected from 44 wells in the Ramganga Sub-Basin (RSB),
      India, and analysed for major ions, nutrients and trace metals. The primary goal
      of this study is to evaluate the hydrochemistry and to identify the geochemical
      processes that govern the water chemistry in the shallow and deep tube wells in
      the study area using geochemical methods. The knowledge of changes in
      hydrochemistry of the aquifers is important for both groundwater recharge and use
      in the region. This study found that there are substantial differences of water
      chemistry between shallow and deep wells. In the shallow wells, the average
      concentrations of total dissolved solid (TDS), Na, K, Ca, Mg, HCO3, Cl, SO4, NO3,
      PO4, F, Cu, Mn, Fe and Cr are twofold higher than the deep wells. The
      concentrations of dissolved silica in the groundwater do not vary with the depth,
      which implies that the variation in the water chemistry is not due to mineral
      dissolution alone. Major ion ratios and saturation indices suggest that the water
      chemistry is predominantly controlled by dissolution of carbonate minerals,
      silicate weathering and ion exchange reactions. Thermodynamic evaluation (ion
      activity ratios and stability filed diagrams) indicates that the kaolinite and
      gibbsite controlled the water chemistry in the both shallow and deep wells. In
      addition, the groundwater chemistry in the shallow wells is affected by the
      vertical infiltration of contaminated water from surface contamination sources
      and nitrification process. In the deep wells, absence of NO3 and low
      concentrations of Cl, SO4, PO4 and F imply the role of regional flow and
      denitrification in the groundwater. Results concluded that proper management plan
      is necessary to protect the shallow aquifer in the RSB since shallow aquifer
      pumping is less expensive than the deeper one.

PMID- 28744686
TI  - Polycondensation of Asparagine-comprising Dipeptides in Aqueous Media-A
      Simulation of Polypeptide Formation in Primordial Earth Hydrosphere.
AB  - Asparagine and aspartic acid might have mutually transformed in the primordial
      hydrosphere of the earth, if ammonia and aspartic acid had existed in
      equilibrium. These amino acids seem to contribute to polypeptides, while the
      simple amino acids glycine and alanine easily form cyclic dipeptides and do not
      achieve long peptide chains. Asparagine-comprising dipeptides contribute some
      kinds of activation forms of dipeptides because these can polymerize faster than
      asparagine only. The new finding of polypeptide formation suggests a pathway of
      sequential polypeptides to evolve a diversity of polypeptides.

PMID- 28744687
TI  - LIN28A, a sensitive immunohistochemical marker for Embryonal Tumor with
      Multilayered Rosettes (ETMR), is also positive in a subset of Atypical
      Teratoid/Rhabdoid Tumor (AT/RT).
AB  - INTRODUCTION: CNS embryonal tumors comprise a group of highly malignant neoplasms
      with a wide spectrum of histomorphological entities that includes Medulloblastoma
      (MB), Atypical Teratoid/Rhabdoid Tumor (AT/RT), Neuroblastoma (NB),
      Ganglioneuroblastoma (GNB), Embryonal Tumor with Multilayered Rosettes (ETMR),
      and the embryonal tumor-Not Otherwise Specified (NOS). The entity ETMR includes
      previously described histopathologic patterns-Embryonal Tumor with Abundant
      Neuropil and True Rosettes (ETANTR), Ependymoblastoma (EBL), and
      Medulloepithelioma (MEPL). Based on the histopathological similarities
      (multilayered rosettes) among ETANTR, EBL, and MEPL, as well as uniform clinical
      behavior and common molecular genetic characteristics, the WHO revision has
      created a new entity, "ETMR." Immunoreactivity of LIN28A has been identified as a
      sensitive tool for the diagnosis of this entity. Since there is a paucity of
      literature regarding immunoreactivity of LIN28A across all embryonal CNS tumors,
      the present study was undertaken. MATERIALS AND METHODS: During the 5-year study
      period (2012 to 2016), all the embryonal tumors (MB, AT/RT, other embryonal
      tumors-ETANTR, MEPL, PNET) that had been earlier diagnosed in the department of
      neuropathology (cases operated in our institute as well as received as referral)
      were reviewed. The archived Hematoxylin and Eosin (H&E) and the available
      immunohistochemistry (IHC) sections were studied. Further, for the other
      embryonal tumors where the paraffin blocks were available, an extended panel of
      IHC was performed for confirming the diagnosis of embryonal tumor and only
      confirmed cases were included in the study. The demographic details of the study
      cohort were noted. IHC for LIN28A was performed on conventional sections.
      RESULTS: A total of 396 cases of embryonal tumors including 302 MB, 72 AT/RT, and
      22 other embryonal tumors were diagnosed during the study period. Among these, 80
      MB, 35 AT/RT, 4 ETANTR, 1 MEPL, 4 NB, 2 GNB, and 1 CNS embryonal tumor-NOS (total
      127) were included for the study. LIN28A immunoreactivity was absent in all MB,
      GNB, NB, and CNS embryonal tumors-NOS whereas all cases of ETMR (4 ETANTR, 1
      MEPL) and 8/35 (23%) of AT/RT showed immunopositivity for LIN28A, which was
      patchy and distinct in most of the cases of ETMR. CONCLUSION: Our study
      reiterates that LIN28A is a sensitive IHC marker for the diagnosis of ETMR. We
      also show that among CNS embryonal tumors, LIN28A is not specific to ETMRs and
      such immunoreactivity can also be seen in a proportion of AT/RTs.

PMID- 28744688
TI  - Intracranial extradural arachnoid cyst in a child.
AB  - INTRODUCTION: Arachnoid cysts are benign developmental anomalies of arachnoid
      membrane origin that can occur anywhere along the neuro-axis. They are believed
      to develop from the splitting or duplication of the arachnoid membrane by CSF
      that is trapped by a ball-valve mechanism. Intracranial arachnoid cysts have only
      been described as intradural lesions while spinal arachnoid cysts can be both
      intradural or extradural. CASE REPORT: After an extensive literature review, we
      report the first case of an intracranial, extradural arachnoid cyst in a 5
      yearold girl. The child presented with a 2-week history of suspected seizure-like
      activity and imaging revealed a large midline extradural CSF-containing arachnoid
      cyst causing severe compression of the superior sagittal sinus and underlying
      brain. Venous flow through the sagittal sinus was nearly obliterated. Osseous
      changes and bone growth adjacent to the cyst was also noted on imaging and
      intraoperatively. She underwent a bifrontal craniotomy and cyst excision with
      decompression of underlying brain and reestablishment of venous flow through the
      sagittal sinus.

PMID- 28744689
TI  - Pediatric cerebellar giant cavernous malformation: case report and review of
      literature.
AB  - BACKGROUND AND IMPORTANCE: Giant cavernous malformations (GCM) are low flow,
      angiographically occult vascular lesions, with a diameter >4 cm. Cerebellar GCMs
      are extremely rare, with only seven cases reported based on English literature.
      These lesions are most commonly seen in the pediatric age group, which is known
      to have an increased risk of hemorrhage, being surgery clearly recommended.
      CLINICAL PRESENTATION: An 18-month-old girl presented with a 6-month history of
      cervical torticollis and upper extremities clumsiness. An MRI revealed a 57 * 46
      * 42 mm multi-cystic, left cerebellar hemisphere mass, showing areas of
      hemorrhages and cysts with various stages of thrombus. There was no enhancement
      with contrast. Cerebral angiography ruled out an arteriovenous malformation. She
      underwent a left paramedian occipital craniotomy, and macroscopic gross total
      resection was accomplished. Histopathologic examination was consistent with a
      cavernous malformation. After surgery, the patient had no new neurological
      deficit and an uneventful postoperative recovery. Follow-up MRI confirmed total
      removal of the lesion. CONCLUSION: Cerebellar GCMs in children are symptomatic
      lesions, which prompt immediate surgical treatment. These are rare lesions, which
      can radiologically and clinically mimic a tumor with bleed, having to be
      considered in the differential diagnosis of neoplastic lesions. Cerebellar GCMs
      might be suspected in the presence of large hemorrhagic intra-axial mass with
      "bubbles of blood," multi-cystic appearance, surrounded by hemosiderin ring,
      fluid-fluid levels, and accompanying edema-mass effect. Careful radiological
      study provides a preoperative diagnosis, but its confirmation requires
      histopathological examination. Complete surgical removal should be attempted when
      possible.

PMID- 28744690
TI  - Giant occipital aneurysmal bone cyst caused to hydrocephalus in a child.

PMID- 28744691
TI  - Safety of intravitreal clindamycin in albino rabbit eyes.
AB  - PURPOSE: To study the potential toxic effects of intravitreal clindamycin on the
      retina of albino rabbits, by assessing functional and morphological retinal
      changes. METHODS: Eight albino rabbits were included in the study. In each
      rabbit, 1 mg/0.1 ml clindamycin was injected into the vitreous of the right
      (experimental) eye, and 0.1 ml saline was injected into the vitreous of the left
      (control) eye. The electroretinogram (ERG) was recorded before injection, 3 days,
      1, 2, and 4 weeks post-injection. The visual evoked potential (VEP) was recorded
      4 weeks post-injection. Clinical examination was conducted at all time points.
      The eyes were enucleated at the termination of the follow-up period in order to
      prepare the retinas for histology in order to assess retinal structure. RESULTS:
      ERG and VEP responses that were recorded from the experimental eye at different
      times following intravitreal clindamycin injection were very similar to the
      corresponding responses that were recorded from the control eyes. Clinical
      examination was normal in all eyes, and no histological damage was observed.
      CONCLUSIONS: Intravitreal injection of 1 mg clindamycin does not cause functional
      or morphological signs of retinal toxicity in albino rabbits, during a period of
      4 weeks post-injection. These findings support the clinical use of 1 mg
      intravitreal clindamycin.

PMID- 28744692
TI  - Frequency of acute longus colli tendinitis on CT examinations.
AB  - PURPOSE: We attempted to determine the frequency of acute longus colli tendinitis
      on diagnostic CT imaging performed at a large multicenter health care system. By
      correlating with the pre-imaging clinical information, we investigated which
      patient presentations should lead the radiologist to increased suspicion for this
      condition. METHODS: Images from a total of 8101 adult CT examinations of the neck
      and cervical spine performed over a 3-month period were evaluated by researchers
      independent of the original clinical report. Clinical information available at
      the time of imaging was reviewed and assigned to one of five categories.
      Frequency of the condition was calculated by sex and clinical presentation. This
      retrospective study with waiver of consent and waiver of HIPPA was approved by
      our IRB. RESULTS: Nine positive scans were found for an overall frequency of 1.1
      per 1000 examinations. The frequency was significantly higher (11.4 per thousand)
      on scans performed of patients presenting without history of recent trauma,
      concern for tumor, suspected postoperative complication, or clinical signs of
      infection localized to the neck. Although frequency in males was higher than in
      females, this did not reach statistical significance. In no positive or negative
      case was longus colli tendinitis considered in the pre-imaging documentation.
      CONCLUSIONS: Findings of acute longus colli tendinitis on CT examination
      generally occur in the absence of prior mention of this condition in the medical
      record. The radiologist should be particularly alert for this diagnosis when a
      patient presents with rapid-onset neck pain without a clear history of recent
      trauma or other etiologies.

PMID- 28744693
TI  - VEGFA Involves in the Use of Fluvastatin and Zoledronate Against Breast Cancer.
AB  - Our study aimed to identify key genes involved in the use of fluvastatin and
      zoledronate against breast cancer, as well as to investigate the roles of
      vascular endothelial growth factor A (VEGFA) in the malignant behaviors of breast
      cancer cells. The expression data GSE33552 was downloaded from Gene Expression
      Omnibus database, including mocked-, fluvastatin- and zoledronate-treated MDA-MB
      231 cells. Differentially expressed genes (DEGs) were identified in fluvastatin-
      and zoledronate-treated cells using limma package, respectively. Pathway
      enrichment analysis and protein-protein interaction (PPI) network analysis were
      then performed. Then we used shRNA specifically targeting VEGFA (shVEGFA) to
      knock down the expression of VEGFA in MDA-MB-231 cells. Cell viability assay,
      scratch wound healing assay, Transwell invasion assay and flow cytometry were
      performed to explore the effects of VEGFA knockdown on the malignant behaviors of
      breast cancer cells. VEGFA was up-regulated in both fluvastatin- and zoledronate
      treated breast cancer cells. Moreover, VEGFA was a hub node in PPI network. In
      addition, VEGFA was successfully knocked down in MDA-MB-231 cells by shVEGFA.
      Suppression of VEGFA promoted the migration and invasion of breast cancer MDA-MB
      231 cells. Suppression of VEGFA inhibited the apoptosis of MDA-MB-231 cells. Our
      results indicate that up-regulation of VEGFA may prevent the progression of
      breast cancer after fluvastatin and zoledronate treatment via inducing cell
      apoptosis and inhibiting migration and invasion. VEGFA may serve as a potential
      prognostic indicator for clinical outcome in the management of breast cancer.

PMID- 28744694
TI  - Structural and functional diversity of caspase homologues in non-metazoan
      organisms.
AB  - Caspases, the proteases involved in initiation and execution of metazoan
      programmed cell death, are only present in animals, while their structural
      homologues can be found in all domains of life, spanning from simple prokaryotes
      (orthocaspases) to yeast and plants (metacaspases). All members of this wide
      protease family contain the p20 domain, which harbours the catalytic dyad formed
      by the two amino acid residues, histidine and cysteine. Despite the high
      structural similarity of the p20 domain, metacaspases and orthocaspases were
      found to exhibit different substrate specificities than caspases. While the
      former cleave their substrates after basic amino acid residues, the latter
      accommodate substrates with negative charge. This observation is crucial for the
      re-evaluation of non-metazoan caspase homologues being involved in processes of
      programmed cell death. In this review, we analyse the structural diversity of
      enzymes containing the p20 domain, with focus on the orthocaspases, and summarise
      recent advances in research of orthocaspases and metacaspases of cyanobacteria,
      algae and higher plants. Although caspase homologues were initially proposed to
      be involved in execution of cell death, accumulating evidence supports the role
      of metacaspases and orthocaspases as important contributors to cell homeostasis
      during normal physiological conditions or cell differentiation and ageing.

PMID- 28744695
TI  - Update of the ICUD-SIU consultation on stone technology behind ureteroscopy.
AB  - INTRODUCTION: Ureteroscopy is now the most frequent treatment used around the
      world for stone disease. Technological advancement, efficiency, safety, and
      minimally invasiveness of this procedure are some of the reasons for this change
      of trend. MATERIALS AND METHODS: In this review of the literature, a search of
      the PubMed database was conducted to identify articles related to ureteroscopy
      and accessories. The committee assigned by the International Consultation on
      Urological Disease reviewed all the data and produced a consensus statement
      relating to the ureteroscopy and all the particularities around this procedure.
      CONCLUSION: This manuscript provides literatures and recommendations for
      endourologists to keep them informed in regard to the preoperative,
      intraoperative, and postoperative consideration in regard of a ureteroscopy.

PMID- 28744696
TI  - A letter of reply to: Salehmohamed, M.R., Griffin, M., Branigan, T. et al.
      Patients treated with immunosuppressive steroids are less aware of sick day rules
      than those on endocrine replacement therapy and may be at greater risk of adrenal
      crisis. Ir J Med Sci (2017). doi:10.1007/s11845-017-1607-y.

PMID- 28744697
TI  - Prospective validation of neutrophil-to-lymphocyte ratio as a diagnostic and
      management adjunct in acute appendicitis.
AB  - BACKGROUND: No optimal biomarker exists that accurately diagnoses appendicitis or
      predicts severity, estimates post-operative complications or total length of
      hospital stay (LOS). AIM: To prospectively validate the utility of neutrophil-to
      lymphocyte (NLR) ratio in predicting the severity of appendicitis, LOS, and 30
      day complication rates. METHODS: Patients who were admitted with a provisional
      diagnosis of acute appendicitis over a period of 18 months (Oct 2014-April 2016)
      were included. Patient demographics and blood results were prospectively
      collected. Details of imaging, operative intervention, severity of appendicitis,
      length of stay, and 30-days post admission complications were recorded.
      Recommended cut-off values of NLR and C-reactive protein for severity of
      appendicitis were determined using receiver operating characteristic analysis
      (ROC). These cut-off values were compared with C-reactive protein levels. Mann
      Whitney test was performed to assess the correlations between LOS and 30-day
      complications to NLR. RESULTS: Four hundred fifty-three patients were included in
      the study; 55.2% (n = 245) were female with mean patient age of 23 years. Two
      thirds (n = 281, 62.03%) underwent operative management. Histologically,
      appendicitis was confirmed in 214 (76%) patients. A NLR of >6.36 or CRP of >28
      were statistically associated with complicated acute appendicitis, with a median
      of one extra hospital day (p < 0.0001). Mean NLR was statistically higher in
      patients with post-operative complications (14.42 vs. 7.29 for simple
      appendicitis group, p < 0.001). CONCLUSION: This confirms previous reports that
      NLR is a simple, readily available adjunct in predicting severity of
      appendicitis. Additionally, it can aid delineating severe appendicitis that
      should proceed to surgery without substantial delay.

PMID- 28744698
TI  - Association of basal serum androgen levels with ovarian response and ICSI cycle
      outcome.
AB  - BACKGROUND: The purpose of this study was to assess the predictive value of basal
      serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during
      follicular phase for ovarian response and outcome in intracytoplasmic sperm
      injection (ICSI) cycles of women with diminished ovarian reserve. METHODS: We
      prospectively gathered data of basal serum androgen levels and ICSI cycle
      characteristics of 120 women with diminished ovarian reserve. Association of
      basal serum T and DHEAS levels with ovarian response was analyzed. RESULTS: Basal
      T and DHEAS levels were similar between pregnant and non-pregnant cases (P >
      0.05). There were significant differences between groups with and without
      successful embryo implantation in terms of serum follicle-stimulating hormone
      (FSH), anti-Mullerian hormone (AMH), gonadotropin starting and total dose, and
      peak estradiol level (P < 0.05). There were 58 (49.2%) cases who did not reach to
      the embryo transfer stage due to several reasons including cancelation of
      stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup
      (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or
      embryo development (n = 15, 12.5%). Basal androgen levels were not significant
      predictors for any of the cycle outcome. AMH level was a significant predictor
      for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and
      cancelation of stimulation (AUC 0.801, P < 0.001). FSH was a significant
      predictor for cancelation of stimulation (AUC 0.774, P < 0.001). CONCLUSION: In
      women with diminished ovarian reserve, basal T and DHEAS levels have no value in
      predicting any of the cycle outcome parameters.

PMID- 28744699
TI  - Evaluating Iowa Severe Maternal Morbidity Trends and Maternal Risk Factors: 2009
      2014.
AB  - Objectives To describe statewide SMM trends in Iowa from 2009 to 2014 and
      identify maternal characteristics associated with SMM, overall and by age group.
      Methods We used 2009-2014 linked Iowa birth certificate and hospital discharge
      data to calculate SMM based on a 25-condition definition and 24-condition
      definition. The 24-condition definition parallels the 25-condition definition,
      but excludes blood transfusions. We calculated SMM rates for all delivery
      hospitalizations (N = 196,788) using ICD-9-CM diagnosis and procedure codes. We
      used log-binomial regression to assess the association of SMM with maternal
      characteristics, overall and stratified by age groupings. Results In contrast to
      national rates, Iowa's 25-condition SMM rate decreased from 2009 to 2014. Based
      on the 25-condition definition, SMM rates were significantly higher among women
      <20 years and >34 years compared to women 25-34 years. Blood transfusion was the
      most prevalent indicator, with hysterectomy and disseminated intravascular
      coagulation (DIC) among the top five conditions. Based on the 24-condition
      definition, younger women had the lowest SMM rates and older women had the
      highest SMM rates. SMM rates were also significantly higher among racial/ethnic
      minorities compared to non-Hispanic white women. Payer was the only risk factor
      differentially associated with SMM across age groups. First trimester prenatal
      care initiation was protective for SMM in all models. Conclusions High rates of
      blood transfusion, hysterectomy, and DIC indicate a need to focus on reducing
      hemorrhage in Iowa. Both younger and older women and racial/ethnic minorities are
      identified as high risk groups for SMM that may benefit from special
      consideration and focus.

PMID- 28744700
TI  - Evaluation of the Completeness, Data Quality, and Timeliness of Fetal Mortality
      Surveillance in Wyoming, 2006-2013.
AB  - Purpose The number of fetal deaths in the United States each year exceeds that of
      infant deaths. High quality fetal death certificate data are necessary for states
      to effectively address preventable fetal deaths. We evaluated completeness of
      detection of fetal deaths among Wyoming residents that occur out-of-state,
      quality of cause-of-death data, and timeliness of Wyoming fetal death certificate
      registration during 2006-2013. Description The numbers of out-of-state fetal
      deaths among Wyoming residents recorded by Wyoming surveillance and reported by
      the National Vital Statistics System were compared. Quality of cause-of-death
      data was assessed by calculating percentage of fetal death certificates completed
      in Wyoming with ill-defined, unknown, or missing cause-of-death entries.
      Timeliness was determined using the time between the fetal death and filing of
      the fetal death certificate with the Wyoming Department of Health Vital
      Statistics Service. Assessment Wyoming surveillance detected none of the 76 out
      of-state fetal deaths among Wyoming residents reported by the National Vital
      Statistics System. Among 263 fetal death certificates completed in Wyoming and
      collected by Wyoming surveillance, 108 (41%) contained ill-defined, unknown, or
      missing cause-of-death entries. Median duration between the fetal death and
      filing with the Wyoming Vital Statistics Service was 33 days. Conclusion Wyoming
      fetal mortality surveillance is limited by failure to register out-of-state fetal
      deaths among residents, poor quality of cause-of-death data, and lack of
      timeliness. Strategies to improve surveillance include automating
      interjurisdictional sharing of fetal death data, certifier education, and
      electronic fetal death registration.

PMID- 28744701
TI  - Aging and visual 3-D shape recognition from motion.
AB  - Two experiments were conducted to evaluate the ability of younger and older
      adults to recognize 3-D object shape from patterns of optical motion. In
      Experiment 1, participants were required to identify dotted surfaces that rotated
      in depth (i.e., surface structure portrayed using the kinetic depth effect). The
      task difficulty was manipulated by limiting the surface point lifetimes within
      the stimulus apparent motion sequences. In Experiment 2, the participants
      identified solid, naturally shaped objects (replicas of bell peppers, Capsicum
      annuum) that were defined by occlusion boundary contours, patterns of specular
      highlights, or combined optical patterns containing both boundary contours and
      specular highlights. Significant and adverse effects of increased age were found
      in both experiments. Despite the fact that previous research has found that
      increases in age do not reduce solid shape discrimination, our current results
      indicated that the same conclusion does not hold for shape identification. We
      demonstrated that aging results in a reduction in the ability to visually
      recognize 3-D shape independent of how the 3-D structure is defined (motions of
      isolated points, deformations of smooth optical fields containing specular
      highlights, etc.).

PMID- 28744702
TI  - Visuo-haptic integration in object identification using novel objects.
AB  - Although some studies have shown that haptic and visual identification seem to
      rely on similar processes, few studies have directly compared the two. We
      investigated haptic and visual object identification by asking participants to
      learn to recognize (Experiments 1, and 3), or to match (Experiment 2) novel
      objects that varied only in shape. Participants explored objects haptically,
      visually, or bimodally, and were then asked to identify objects haptically and/or
      visually. We demonstrated that patterns of identification errors were similar
      across identification modality, independently of learning and testing condition,
      suggesting that the haptic and visual representations in memory were similar. We
      also demonstrated that identification performance depended on both learning and
      testing conditions: visual identification surpassed haptic identification only
      when participants explored the objects visually or bimodally. When participants
      explored the objects haptically, haptic and visual identification were
      equivalent. Interestingly, when participants were simultaneously presented with
      two objects (one was presented haptically, and one was presented visually),
      object similarity only influenced performance when participants were asked to
      indicate whether the two objects were the same, or when participants had learned
      about the objects visually-without any haptic input. The results suggest that
      haptic and visual object representations rely on similar processes, that they may
      be shared, and that visual processing may not always lead to the best
      performance.

PMID- 28744703
TI  - Pathways of Intergenerational Transmission of Advantages during Adolescence:
      Social Background, Cognitive Ability, and Educational Attainment.
AB  - Educational attainment in adolescence is of paramount importance for attaining
      higher education and for shaping subsequent life chances. Sociological accounts
      focus on the role of differences in socioeconomic resources in intergenerational
      reproduction of educational inequalities. These often disregard the
      intergenerational transmission of cognitive ability and the importance of
      children's cognitive ability to educational attainment. Psychological
      perspectives stress the importance of cognitive ability for educational
      attainment but underemphasize potentially different roles of specific
      socioeconomic resources in shaping educational outcomes, as well as individual
      differences in cognitive ability. By integrating two strands of research, a
      clearer picture of the pathways linking the family of origin, cognitive ability,
      and early educational outcomes can be reached. Using the population-based
      TwinLife study in Germany, we investigated multidimensional pathways linking
      parental socioeconomic position to their children's cognitive ability and
      academic track attendance in the secondary school. The sample included twins (N =
      4008), respectively ages 11 and 17, and siblings (N = 801). We observed strong
      genetic influences on cognitive ability, whereas shared environmental influences
      were much more important for academic tracking. In multilevel analyses, separate
      dimensions of socioeconomic resources influenced child cognitive ability,
      controlling parental cognitive ability. Controlling adolescent cognitive ability
      and parental cognitive ability, parental socioeconomic resources also directly
      affected track attendance. This indicated that it is crucial to investigate the
      intertwined influences on educational outcomes in adolescence of both cognitive
      ability and the characteristics of the family of origin.

PMID- 28744704
TI  - Subjective cognitive decline in patients with migraine and its relationship with
      depression, anxiety, and sleep quality.
AB  - BACKGROUND: Cognitive decline is a major concern in patients with migraine.
      Depression, anxiety, and/or poor sleep quality are well-known comorbidities of
      migraine, but available evidence on the subjective cognitive decline (SCD) is
      limited. This study aimed to investigate the presence and frequency of SCD and
      its relationship with anxiety, depression and sleep quality in patients with
      migraine. METHODS: We enrolled patients with migraine who scored within the
      normal range of the Korean-Mini Mental State Examination and the Korean-Montreal
      Cognitive Assessment. Using the Subjective Cognitive Decline Questionnaire (SCD
      Q), participants with >=7 were assigned to the SCD group. The Headache Impact
      Test-6, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and
      Pittsburgh Sleep Quality Index were used and analyzed between the two groups.
      RESULTS: A total of 188 patients with migraine, aged 38.1 +/- 9.9 years, were
      enrolled. The mean SCD-Q score was 6.5 +/- 5.5, and 44.7% of participants were
      identified as SCD. Migraineurs with SCD reported higher headache pain intensity
      and headache impact, as well as greater prevalence of anxiety, depression,
      reduced quality of sleep, and shorter sleep duration during weekdays compared to
      migraineurs without SCD. There were no significant differences in terms of age,
      sex, migraine type (chronic/episodic), medication, or sleep duration during
      weekends between the two groups. Upon multivariate logistic analysis adjusted for
      age, sex, headache characteristics, and psychological variables, depression was
      associated with increased risk of SCD (Odds ratio 1.31, 95% confidence interval
      1.16-1.49) and sleep duration during weekdays was associated with decreased risk
      of SCD (Odds ratio 0.66, 95% confidence interval 0.44-0.97). CONCLUSIONS: A non
      negligible number of patients with migraine complained of SCD. Depression and
      short sleep duration during weekdays were related to SCD among adult migraineurs.

PMID- 28744705
TI  - The Growth of Hospitalists and the Future of the Society of General Internal
      Medicine: Results from the 2014 Membership Survey.
AB  - According to the most recent annual membership surveys, hospitalists are a
      rapidly growing component of the Society of General Internal Medicine (SGIM).
      Should this trend continue, hospitalists could increase from 22% of SGIM
      membership in 2014 to nearly 33% by 2020. Only 34% of hospitalists who responded
      to the survey, however, consider SGIM their academic home, compared to 54% of non
      hospitalist respondents. Based on these survey findings, it is clear that the
      landscape of general internal medicine is changing with the growth of
      hospitalists, and SGIM will need to strategize to keep these hospitalist members
      actively engaged in the organization.

PMID- 28744706
TI  - The evolution of a G1/S transcriptional network in yeasts.
AB  - The G1-to-S cell cycle transition is promoted by the periodic expression of a
      large set of genes. In Saccharomyces cerevisiae G1/S gene expression is regulated
      by two transcription factor (TF) complexes, the MBF and SBF, which bind to
      specific DNA sequences, the MCB and SCB, respectively. Despite extensive research
      little is known regarding the evolution of the G1/S transcription regulation
      including the co-evolution of the DNA binding domains with their respective DNA
      binding sequences. We have recently examined the co-evolution of the G1/S TF
      specificity through the systematic generation and examination of chimeric
      Mbp1/Swi4 TFs containing different orthologue DNA binding domains in S.
      cerevisiae (Hendler et al. in PLoS Genet 13:e1006778. doi:
      10.1371/journal.pgen.1006778 , 2017). Here, we review the co-evolution of G1/S
      transcriptional network and discuss the evolutionary dynamics and specificity of
      the MBF-MCB and SBF-SCB interactions in different fungal species.

PMID- 28744707
TI  - Aortic dissection, a diagnostic challenge.

PMID- 28744708
TI  - Topics of nuclear medicine research in Europe.
AB  - Last year in the European Journal of Nuclear Medicine and Molecular Imaging, we
      introduced some recent nuclear medicine research conducted in Japan. This was
      favorably received by European readers in the main. This year we wish to focus on
      the Annals of Nuclear Medicine on some of the fine nuclear medicine research work
      executed in Europe recently. In the current review article, we take up five
      topics: prostate-specific membrane antigen imaging, recent advances in
      radionuclide therapy, [18F]fluorodeoxyglucose positron-emission tomography (PET)
      for dementia, quantitative PET assessment of myocardial perfusion, and iodine-124
      (124I). Just at the most recent annual meeting of the European Association of
      Nuclear Medicine 2016, Kyoto was selected as the host city for the 2022 Congress
      of the World Federation of Nuclear Medicine and Biology. We hope that our
      continuous efforts to strengthen scientific cooperation between Europe and Japan
      will bring many European friends and a great success to the Kyoto meeting.

PMID- 28744709
TI  - Is it Useful to Look into Airways in Non-Resolving Pneumonia?

PMID- 28744710
TI  - Outcome of Extreme Preterm Babies Treated with Ventriculo-Peritoneal Shunt for
      Post Hemorrhagic Hydrocephalus.

PMID- 28744711
TI  - Calcitriol Ameliorates AngiotensinII-Induced Renal Injury Partly via Upregulating
      A20.
AB  - Inflammation and reactive oxygen species (ROS) play crucial roles in the
      progression of chronic kidney diseases. Vitamin D has been shown anti
      inflammatory effects, but the underlying mechanism is not fully understood. Here,
      we investigated whether calcitriol exerts protective effects via upregulating A20
      in angiotensinII (AngII)-induced renal injury. Male C57BL/6 mice were infused
      with vehicle or AngII for 10 days. Calcitriol reduced infiltration of T
      lymphocytes and macrophages. This reduction of inflammatory cells was accompanied
      by elevated A20 and decreased pro-inflammatory cytokines (PICs) and reactive
      oxygen species (ROS). Calcitriol could inhibit NF-kappaB activation and
      necroptotic pathway. Induction of A20 was located primarily to the tubular
      epithelial cells. In rat proximal tubular epithelial cells (NRK-52E), calcitriol
      stably upregulated A20 and reduced the PICs and ROS. Inhibitory effect of A20 on
      PICs and ROS depended on suppressing NF-kappaB pathway and necroptotic pathway,
      respectively. A20 knockdown diminished the effect of calcitriol on suppressing NF
      kappaB and necroptotic pathways. However, A20 deficiency could not abrogate the
      inhibitory effect of calcitriol on NF-kappaB and necroptotic pathways. Our
      results established that A20 is involved in the renoprotective effect by
      calcitriol via negatively modulating the NF-kappaB pathway and necroptotic
      pathway in AngII-induced renal injury.

PMID- 28744712
TI  - Vacuolar Protein Sorting 4B (VPS4B) Regulates Apoptosis of Chondrocytes via p38
      Mitogen-Activated Protein Kinases (MAPK) in Osteoarthritis.
AB  - To aim of this study is to investigate the expression of VPS4B (vacuolar protein
      sorting 4B) in articular cartilage with osteoarthritis (OA) and to analyze the
      relationship between VPS4B and chondrocyte apoptosis. We established an OA rat
      model by the MLI (meniscal/ligamentous injury) modeling method, and we observed
      the expression of VPS4B in articular cartilage through immunohistochemistry and
      reverse transcription polymerase chain reaction (RT-PCR). Human SW1353
      chondrosarcoma cells were treated with IL-1beta to mimic the OA-like chondrocyte
      injury in vitro, and Western blot was employed to examine the IL-1beta-induced
      expression of VPS4B, phosphorylated p38, and apoptotic markers, namely active
      caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP). The co-localization of
      VPS4B and active caspase 3 was confirmed through immunofluorescence. We knocked
      down VPS4B expression through RNA interference. Western blot was carried out to
      detect the knockdown efficiency of VPS4B and evaluate its effects on IL-1beta
      stimulated expression of apoptotic markers and phosphorylated p38 in SW1353
      cells. Annexin V/propidium iodide (PI) staining was used to detect chondrocyte
      apoptosis. VPS4B expression was significantly upregulated in articular cartilage
      of OA rat model. IL-1beta stimulation increased the expression of VPS4B,
      apoptotic markers, and phosphorylated p38 in SW1353 cells. VPS4B co-localized
      with active caspase 3 in IL-1beta-treated SW1353 cells. VPS4B inhibition
      significantly reduced IL-1beta-stimulated expression of apoptotic markers and
      phosphorylated p38 in SW1353 cells. Moreover, flow cytometry assay demonstrated
      that VPS4B knockdown alleviated IL-1beta-induced apoptosis. Our results suggested
      that VPS4B might facilitate chondrocyte apoptosis in OA via p38 MAPK signaling
      pathway. This study may provide a novel insight into the pathophysiology of OA
      and a potential therapeutic target for its treatment.

PMID- 28744713
TI  - Genome-wide analysis of gene expression profiling revealed that COP9 signalosome
      is essential for correct expression of Fe homeostasis genes in Arabidopsis.
AB  - In plant cells, either excess or insufficient iron (Fe) concentration triggers
      stress responses, therefore it is strictly controlled. Proteasome-mediated
      degradation through ubiquitination of Fe homeostasis proteins has just become the
      focus of research in recent years. Deactivating ubiquitin ligases, COP9
      signalosome has a central importance in the translational control of various
      stress responses. The aim of the study was to investigate COP9 signalosome in Fe
      deficiency response of Strategy I plants. In silico analysis of a set of Fe
      deficiency-responsive genes was conducted against the transcriptome of
      Arabidopsis csn mutant lines using Genevestigator software. Induced and
      suppressed genes were clustered in a hierarchical way and gene ontology
      enrichment categories were identified. In wild-type Arabidopsis, CSN genes did
      not respond to iron deficiency. In csn mutant lines, under Fe-sufficient
      conditions, hundreds of Fe-deficiency-responsive genes were misregulated. Among
      the ones previously characterized for their physiological roles under Fe
      deficiency IRT1, NAS4, BTS, NRAMP1 were down-regulated while AHA2, MTP8, FRD3
      were up-regulated. Unexpectedly, from those which were regulated in opposite
      ways, some had been repeatedly shown to be tightly co-regulated by the same
      transcription factor, FIT. Two proteins from DELLA family, which were reported to
      interact with FIT to repress its downstream, were found to be strikingly
      repressed in csn mutants. Overall, the study underlined that the absence of a
      functional CSN greatly impacted the regulation of Fe homeostasis-related genes,
      in a manner which cannot be explained simply by the induction of the master
      transcription factor, FIT. Correct expression of Fe deficiency-responsive genes
      requires an intact COP9 signalosome in Arabidopsis.

PMID- 28744714
TI  - Erratum to: Chronic Paroxetine Treatment Prevents the Emergence of Abnormal
      Electroencephalogram Oscillations in Huntington's Disease Mice.

PMID- 28744715
TI  - Thermal Pretreatment of Harvest Residues and Their Use in Anaerobic Co-digestion
      with Dairy Cow Manure.
AB  - Several batch experiments were conducted on the anaerobic co-digestion of dairy
      cow manure (DCM) with three harvest residues (HR) (soybean straw, sunflower
      stalks, and corn stover). The influence of thermal pretreatment of HR on biogas
      production was investigated, where the HR were thermally pretreated at two
      different temperatures: T = 121  degrees C and T = 175  degrees C, during t = 30
      and t = 90 min, respectively. All anaerobic co-digestion batch experiments were
      performed simultaneously under thermophilic regime, at T = 55  degrees C. Biogas
      and methane yields were significantly improved in experiments performed with corn
      stover thermally pretreated at 175  degrees C for 30 min (491.37 cm3/g VS and
      306.96 cm3/g VS, respectively), if compared to experiments performed with
      untreated corn stover. The highest VS and COD removal rates were also observed in
      the same group of experiments and were 34.5 and 50.1%, respectively. The highest
      biogas and methane yields with soybean straw (418.93 cm3/g VS and 261.44 cm3/g
      VS, respectively) were obtained when soybean straw pretreated at 121  degrees C
      during 90 min. The highest biogas and methane yields with sunflower stalk (393.28
      cm3/g VS and 245.02 cm3/g VS, respectively) were obtained when sunflower stalk
      was pretreated at 121  degrees C during 90 min.

PMID- 28744716
TI  - Predictors of Colorectal Cancer Screening Prior to Implementation of a Large
      Pragmatic Trial in Federally Qualified Health Centers.
AB  - : Colorectal cancer screening can prevent cancer deaths. Federally qualified
      health centers serve a unique patient population that often is not screened.
      Knowing who in this environment is getting screened via fecal testing and via
      colonoscopy can assist in tailoring intervention to raise rates of colorectal
      cancer screening. We examined patient-level and neighborhood-level
      characteristics associated with being up to date with colorectal cancer screening
      guidelines. We also examined associations between these factors and being
      screened with a fecal test. We observed an increase in colorectal cancer
      screening rates from 2010 to 2015. Adjusted analyses revealed that the following
      factors were significantly associated with colorectal cancer screening: aged 65
      or older, having any type of insurance, previous outpatient visits, and current
      or other preventive screenings. Among adults aged 50-75 who were up to date with
      colorectal cancer screening, factors associated with use of fecal testing, as
      opposed to colonoscopy, were: being younger, speaking a non-English language,
      being uninsured, having prior office visits, and having had a flu shot in past
      year. Our findings may inform clinic-based effort to raise rates of colorectal
      cancer screening, especially in the community clinic setting. TRIAL REGISTRATION:
      ClinicalTrials.gov , NCT01742065.

PMID- 28744718
TI  - At least one more reason why.

PMID- 28744717
TI  - Novel Regenerative Therapies Based on Regionally Induced Multipotent Stem Cells
      in Post-Stroke Brains: Their Origin, Characterization, and Perspective.
AB  - Brain injuries such as ischemic stroke cause severe neural loss. Until recently,
      it was believed that post-ischemic areas mainly contain necrotic tissue and
      inflammatory cells. However, using a mouse model of cerebral infarction, we
      demonstrated that stem cells develop within ischemic areas. Ischemia-induced stem
      cells can function as neural progenitors; thus, we initially named them
      injury/ischemia-induced neural stem/progenitor cells (iNSPCs). However, because
      they differentiate into more than neural lineages, we now refer to them as
      ischemia-induced multipotent stem cells (iSCs). Very recently, we showed that
      putative iNSPCs/iSCs are present within post-stroke areas in human brains.
      Because iNSPCs/iSCs isolated from mouse and human ischemic tissues can
      differentiate into neuronal lineages in vitro, it is possible that a clearer
      understanding of iNSPC/iSC profiles and the molecules that regulate iNSPC/iSC
      fate (e.g., proliferation, differentiation, and survival) would make it possible
      to perform neural regeneration/repair in patients following stroke. In this
      article, we introduce the origin and traits of iNSPCs/iSCs based on our reports
      and recent viewpoints. We also discuss their possible contribution to
      neurogenesis through endogenous and exogenous iNSPC/iSC therapies following
      ischemic stroke.

PMID- 28744719
TI  - Optimization of Extrusion Process of Directly Expanded Snacks Based on Potato
      Starch in a Single Step for the Formation of Type IV Resistant Starch.
AB  - Resistant starch type IV (RSIV) can be produced by chemical modifications
      (etherized or esterified) such as conversion, substitution, or cross-linking,
      which can prevent its digestion by blocking enzyme access and forming atypical
      linkages. In this research, the effects of barrel temperature (145.86-174.14 
      degrees C), the screw speed (42.93-57.07 Hz) and derivatization (esterification)
      in the formation of RSIV content of directly expanded snacks (second generation
      snacks) were studied. Potato starch was chemically modified by phosphorylation
      and succinylation, and expanded by using the extrusion cooking process. Snacks
      with phosphorylated starch showed expansion index from 2.57 to 3.23, bulk density
      from 306.19 to 479.00 kg/m3 and RSIV from 43.27 to 55.81%. Snacks with
      succinylated starch had expansion index from 3.52 to 3.82, bulk density from
      99.85 to 134.51 kg/m3 and RSIV from 23.17 to 35.01%. The results found in this
      work showed that it is possible to manufacture extruded directly expanded snacks
      (second-generation snacks) such as a ready-to-eat (RTE) with good physicochemical
      properties and without substantial loss of extrusion functionality, which could
      bring a healthy benefit due to the presence of RSIV.

PMID- 28744720
TI  - Lycodine-Type Lycopodium Alkaloids from the Whole Plants of Huperzia serrata.
AB  - Three new lycodine-type Lycopodium alkaloids, namely 1-methyllycodine (1), 8alpha
      hydroxy-15,16-dehydro-des-N-methyl-alpha-obscurine (2), N-methyl-16
      hydroxyhuperzine B (3), and one new natural lycodine-type Lycopodium alkaloid, N
      methylhuperzine A (4), along with 11 known analogues (5-15), were isolated from
      the whole plants of club moss Huperzia serrata. The structures of 1-4 were
      elucidated on the basis of NMR spectroscopic and mass spectrometry data. Among
      them, compound 1 was the first lycodine-type alkaloid possessing a methyl group
      at C-1. In addition, the structure of 5 was confirmed by the single-crystal X-ray
      crystallography data and its 13C NMR was reported for the first time in current
      study. Compounds 1-5 were tested their BACE1 inhibitory activity.

PMID- 28744723
TI  - [Body modifications and sexual health : Impact of tattoos, body piercing and
      esthetic genital plastic surgery on the sexual health of women and men].
AB  - The present paper addresses the psychological impact of body modifications (e.g.
      tattoos, body piercing and esthetic genital plastic surgery) on the sexual health
      of individuals and refers to past and present research insights. Body
      modifications are understood as invasive interventions on the human body,
      especially interventions on the human skin which result in (semi-)permanent
      changes. Tattoos and body piercing (in particular genital piercing) positively
      affect the sexual satisfaction and the sexual appeal of men and women but there
      is a controversial association with high risk sexual behavior. Moreover, this
      article focuses on esthetic genital plastic surgery based on the increasing
      interest and insights of the impact on female genital self-perception and sexual
      behavior.

PMID- 28744722
TI  - Temporal encoding strategies result in boosts to final free recall performance
      comparable to spatial ones.
AB  - The method of loci is a highly effective mnemonic that recruits existing salient
      memory for spatial locations and uses the information as a scaffold for
      remembering a list of items (Yates, 1966). One possible account for the
      effectiveness of the spatial method of loci comes from the perspective that it
      utilizes evolutionarily preserved mechanisms for spatial navigation within the
      hippocampus (Maguire et al. in Proceedings of the National Academy of Sciences,
      97(8), 4398-4403, 2000; O'Keefe & Nadel, 1978; Rodriguez et al. in Brain Research
      Bulletin, 57(3), 499-503, 2002). Recently, though, neurons representing temporal
      information have also been described within the hippocampus (Eichenbaum in Nature
      Reviews Neuroscience, 15(11), 732-744, 2014; Itskov, Curto, Pastalkova, & Buzsaki
      in The Journal of Neuroscience, 31(8), 2828-2834, 2011; MacDonald, Lepage, Eden,
      & Eichenbaum in Neuron, 71(4), 737-749, 2011; Mankin et al. in Proceedings of the
      National Academy of Sciences, 109(47), 19462-19467, 2012; Meck, Church, & Matell
      in Behavioral Neuroscience, 127(5), 642, 2013), challenging the primacy of
      spatial-based functions to hippocampal processing. Given the presence of both
      spatial and temporal coding mechanisms within the hippocampus, we predicted that
      primarily temporal encoding strategies might also enhance memory. In two
      different experiments, we asked participants to learn lists of unrelated nouns
      using the (spatial) method of loci (i.e., the layout of their home as the
      organizing feature) or using two novel temporal methods (i.e., autobiographical
      memories or using the steps to making a sandwich). Participants' final free
      recall performance showed comparable boosts to the method of loci for both
      temporal encoding strategies, with all three scaffolding approaches demonstrating
      performance well above uninstructed free recall. Our findings suggest that
      primarily temporal representations can be used effectively to boost memory
      performance, comparable to spatial methods, with some caveats related to the
      relative ease with which participants appear to master the spatial versus
      temporal methods.

PMID- 28744724
TI  - Concordance of clinical diagnosis of T classification among physicians for
      locally advanced unresectable thoracic esophageal cancer.
AB  - BACKGROUND: We conducted a multicenter phase II trial assessing chemoselection
      with docetaxel plus 5-fluorouracil and cisplatin induction chemotherapy and
      subsequent conversion surgery for locally advanced, unresectable esophageal
      cancer. The aim of this study was to validate the concordance of clinical T
      diagnosis among physicians in the cases of this trial. METHODS: Computed
      tomography scans and esophagoscopic images of 48 patients taken at baseline were
      centrally reviewed by 6 senior physicians with experience in esophageal oncology.
      Individual reviewers voted for definitive T4, relative T4, relative T3, or
      definitive T3. Discordant diagnoses between reviewers were resolved by the
      majority opinion. The reviewers were blinded to patient clinical outcome data and
      to the vote of the other reviewers. RESULTS: Ninety percent of cases were
      diagnosed as clinical T4 by investigators, while 33.3-75.0% (median 70.8%) of
      cases were judged to be T4 by 6 reviewers. Discordant diagnosis between
      investigators and reviewers occurred in 33% (16/48) of all cases (Cohen's kappa
      coefficient 0.0519), including 12 cases where curative resection was considered
      possible (48%, n = 25) and 4 cases where curative resection was considered
      impossible (17%, n = 23). Critical discordance (one reviewer voted for definitive
      T3 but the other voted for definitive T4, and vice versa) between reviewers
      occurred in 0-12.5% of cases (median 2.1%). CONCLUSIONS: There were inter
      observer variations in clinical diagnosis of the T category of locally advanced,
      unresectable esophageal cancer. Accurate clinical diagnosis of T classification
      is required for determining the optimum treatment for each patient.

PMID- 28744725
TI  - Impact of major different variants of papillary thyroid microcarcinoma on the
      clinicopathological characteristics: the study of 1041 cases.
AB  - BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) has been
      increasing globally in the past few decades. PTMC does not have a distinctive
      morphology that results in differences in biological behavior. The aim of this
      study was to classify PTMCs according to the morphological features and explore
      the relationship with clinicopathological characteristics. Additionally, we
      sought to evaluate whether different variants of PTMC can be an independent
      predictor for lymph mode metastasis when considering other risk factors. METHODS:
      Between December 2014 and December 2015, 1041 PTMC cases undergoing surgical
      resection at Tianjin Medical University Cancer Institute and Hospital were
      reviewed retrospectively. Statistical analysis was performed to investigate the
      independent factors for lymph node metastasis in PTMC. RESULTS: Conventional
      variant PTMC (CPTMC), follicular variant PTMC (FPTMC), and encapsulated variant
      PTMC (EnPTMC) were major variants in PTMC, collectively accounting for 96.7% of
      the entire PTMC cohort.There were significant differences in clinicopathological
      characteristics among the three major variants. The frequency of aggressive
      parameters was significantly different among the three variants, including tumor
      size, minimal extrathyroidal extension (minimal ETE), and lymph node metastasis
      (all P < 0.05), being highest in CPTMC, lowest in EnPTMC, and intermediate in
      FPTMC. FPTMC (OR = 0.642, P = 0.003) and EnPTMC (OR = 0.540, P = 0.041) were
      independent protective factors for lymph node metastasis (LNM). In contrast, male
      gender (OR = 1.836, P = 0.000), age less than 45 years (OR = 1.457, P = 0.009),
      tumor size greater than 0.5 cm (OR = 1.453, P = 0.007), calcification (OR =
      1.465, P = 0.016), minimal ETE (OR = 1.801, P = 0.001), and multifocality (OR =
      1.721, P = 0.000) were independent risk factors for LNM. CONCLUSIONS: The present
      study demonstrates the distinct biological behaviors of the three major PTMC
      variants and establishes an aggressive order of CPTMC ? FPTMC > EnPTMC. It is
      necessary to take into consideration variant-related risks and other independent
      predictors for the determination of lymphadenectomy in patients with PTMC.

PMID- 28744726
TI  - Evaluation of purified recombinant spike fragments for assessment of the presence
      of serum neutralizing antibodies against a variant strain of porcine epidemic
      diarrhea virus.
AB  - Since 2010, variant strains of porcine epidemic diarrhea virus (PEDV) have caused
      disasters in the pork industry. The spike (S) protein, as the major immunity
      eliciting antigen, has previously been used for serological testing and has been
      found to correlate significantly with the results of the serum neutralization
      (SN) test. However, further evaluation of this method is needed as new epidemic
      strains of PEDV emerge. Hence, the main objective of this study was to assess sow
      sera and determine the correlation between enzyme-linked immunosorbent assay
      (ELISA) results (involving a newly isolated GDS01 virus-based ELISA and ELISAs
      based on seven recombinant fragments comprising overlapping S1 and partial S2
      sequences) and SN titers. Furthermore, we determined the reliability of the
      ELISAs based on receiver operating characteristics (ROC) curve analyses. For the
      most promising ELISA, i.e., the SP4 ELISA, the correlation coefficient (r) and
      the area under curve (AUC) were determined to be 0.6113 and 0.8538, respectively.
      In addition, we analyzed the homology of the SP4 sequences obtained from
      different strains (including vaccine strains) and found that various strains
      showed a high degree of homology in this region. Thus, we conclude that SP4 is a
      promising serological testing protein for use in the field.

PMID- 28744727
TI  - Host protein atlastin-1 promotes human immunodeficiency virus (HIV-1)
      replication.

PMID- 28744728
TI  - The non-invasive search for the carotid-cavernous fistula: the added value of the
      4D-CTA.

PMID- 28744729
TI  - Low-angled microcatheter approach for coil embolization of the anterior choroidal
      artery aneurysm.
AB  - PURPOSE: Thromboembolic complication is a serious concern following coil
      embolization for aneurysms involving the anterior choroidal artery (AChA). To
      minimize this complication and to improve packing density, we present a technical
      concept of coil embolization. METHODS: We attempted packing of the aneurysmal sac
      by lowering the microcatheter approach angle into an aneurysm to secure AChA
      origin as well as to improve coil packing density of the aneurysm. This technical
      concept involves approaching the aneurysm sac with an adjusted shaping of the
      microcatheter tip to achieve the effect which was not obtained when the
      microcatheter approach angle into the aneurysm sac was high (>=90 degrees ). We
      evaluated immediate angiographic outcome by the Raymond classification, coil
      packing density, and follow-up results (modified Rankin Scale (mRS) and
      recurrence) in seven aneurysms involving AChA in six patients. RESULTS: We
      achieved immediate angiographic outcome of the Raymond classes I or II with 31%
      mean packing density. The AChA origin was preserved without any procedure-related
      complication. There was neither clinical event (mRS = 0) nor aneurysm recurrence
      confirmed on the source image of magnetic resonance angiography during 6-9 months
      follow-up. CONCLUSIONS: The technical concept of low-angled microcatheter
      approach can be useful to improve coil packing density and to secure AChA origin
      when AChA arises near the aneurysm.

PMID- 28744730
TI  - Relationships between the integrity and function of lumbar nerve roots as
      assessed by diffusion tensor imaging and neurophysiology.
AB  - PURPOSE: Diffusion tensor imaging (DTI) has shown promise in the measurement of
      peripheral nerve integrity, although the optimal way to apply the technique for
      the study of lumbar spinal nerves is unclear. The aims of this study are to use
      an improved DTI acquisition to investigate lumbar nerve root integrity and
      correlate this with functional measures using neurophysiology. METHODS: Twenty
      healthy volunteers underwent 3 T DTI of the L5/S1 area. Regions of interest were
      applied to L5 and S1 nerve roots, and DTI metrics (fractional anisotropy, mean,
      axial and radial diffusivity) were derived. Neurophysiological measures were
      obtained from muscles innervated by L5/S1 nerves; these included the slope of
      motor-evoked potential input-output curves, F-wave latency, maximal motor
      response, and central and peripheral motor conduction times. RESULTS: DTI metrics
      were similar between the left and right sides and between vertebral levels.
      Conversely, significant differences in DTI measures were seen along the course of
      the nerves. Regression analyses revealed that DTI metrics of the L5 nerve
      correlated with neurophysiological measures from the muscle innervated by it.
      CONCLUSION: The current findings suggest that DTI has the potential to be used
      for assessing lumbar spinal nerve integrity and that parameters derived from DTI
      provide quantitative information which reflects their function.

PMID- 28744731
TI  - Plant Community Chemical Composition Influences Trembling Aspen (Populus
      tremuloides) Intake by Sheep.
AB  - Nutrients and plant secondary compounds in aspen (Populus tremuloides) may
      interact with nutrients in the surrounding vegetation to influence aspen use by
      herbivores. Thus, this study aimed to determine aspen intake and preference by
      sheep in response to supplementary nutrients or plant secondary compounds (PSC)
      present in aspen trees. Thirty-two lambs were randomly assigned to one of four
      molasses-based supplementary feeds to a basal diet of tall fescue hay (N = 8)
      during three experiments. The supplements were as follows: (1) high-protein (60%
      canola meal), (2) a PSC (6% quebracho tannins), (3) 25% aspen bark, and (4)
      control (100% molasses). Supplements were fed from 0700 to 0900, then lambs were
      fed fresh aspen leaves collected from stands containing high (Experiment 1, 2) or
      low (Experiment 3) concentrations of phenolic glycosides (PG). In Experiment 2,
      lambs were simultaneously offered aspen, a forb (Lathyrus pauciflorus), and a
      grass (Bromus inermis) collected from the aspen understory. Animals supplemented
      with high protein or tannins showed greater intake of aspen leaves than animals
      supplemented with bark or the control diet (P < 0.05), likely because some
      condensed tannins have a positive effect on protein nutrition and protein aids in
      PSC detoxification. Overall, animals supplemented with bark showed the lowest
      aspen intake, suggesting PSC in bark and aspen leaves had additive inhibitory
      effects on intake. In summary, these results suggest that not only the
      concentration but also the types and proportions of nutrients and chemical
      defenses available in the plant community influence aspen use by herbivores.

PMID- 28744732
TI  - Medicago truncatula Oleanolic-Derived Saponins Are Correlated with Caterpillar
      Deterrence.
AB  - Plant resistance mechanisms to insect herbivory can potentially be bred into
      crops as an important strategy for integrated pest management. Medicago
      truncatula ecotypes inoculated with the rhizobium Ensifer medicae (Sinorhizobium
      medica) WSM419 were screened for resistance to herbivory by caterpillars of the
      beet armyworm, Spodoptera exigua, through leaf and whole plant choice studies;
      TN1.11 and F83005.5 are identified as the least and most deterrent ecotypes,
      respectively. In response to caterpillar herbivory, both ecotypes mount a robust
      burst of plant defensive jasmonate phytohormones. Restriction of caterpillars to
      either of these ecotypes does not adversely affect pest performance. This argues
      for an antixenosis (deterrence) resistance mechanism associated with the F83005.5
      ecotype. Unbiased metabolomic profiling identified strong ecotype-specific
      differences in metabolite profile, particularly in the content of oleanolic
      derived saponins that may act as antifeedants. Compared to the more susceptible
      ecotype, F83005.5 has higher levels of oleanolic-type zanhic acid- and
      medicagenic acid-derived compounds. Together, these data support saponin-mediated
      deterrence as a resistance mechanism of the F83005.5 ecotype and implicates these
      compounds as potential antifeedants that could be used in agricultural
      sustainable pest management strategies.

PMID- 28744733
TI  - Arthropods Associate with their Red Wood ant Host without Matching Nestmate
      Recognition Cues.
AB  - Social insect colonies provide a valuable resource that attracts and offers
      shelter to a large community of arthropods. Previous research has suggested that
      many specialist parasites of social insects chemically mimic their host in order
      to evade aggression. In the present study, we carry out a systematic study to
      test how common such chemical deception is across a group of 22 arthropods that
      are associated with red wood ants (Formica rufa group). In contrast to the
      examples of chemical mimicry documented in some highly specialized parasites in
      previous studies, we find that most of the rather unspecialized red wood ant
      associates surveyed did not use mimicry of the cuticular hydrocarbon recognition
      cues to evade host detection. Instead, we found that myrmecophiles with lower
      cuticular hydrocarbon concentrations provoked less host aggression. Therefore,
      some myrmecophiles with low hydrocarbon concentrations appear to evade host
      detection via a strategy known as chemical insignificance. Others showed no
      chemical disguise at all and, instead, relied on behavioral adaptations such as
      particular defense or evasion tactics, in order to evade host aggression.
      Overall, this study indicates that unspecialized myrmecophiles do not require the
      matching of host recognition cues and advanced strategies of chemical mimicry,
      but can integrate in a hostile ant nest via either chemical insignificance or
      specific behavioral adaptations.

PMID- 28744734
TI  - CORR Insights(r): High Interspecimen Variability in Engagement of the
      Anterolateral Ligament: An In Vitro Cadaveric Study.

PMID- 28744735
TI  - Fast-Slow Bursters in the Unfolding of a High Codimension Singularity and the
      Ultra-slow Transitions of Classes.
AB  - Bursting is a phenomenon found in a variety of physical and biological systems.
      For example, in neuroscience, bursting is believed to play a key role in the way
      information is transferred in the nervous system. In this work, we propose a
      model that, appropriately tuned, can display several types of bursting behaviors.
      The model contains two subsystems acting at different time scales. For the fast
      subsystem we use the planar unfolding of a high codimension singularity. In its
      bifurcation diagram, we locate paths that underlie the right sequence of
      bifurcations necessary for bursting. The slow subsystem steers the fast one back
      and forth along these paths leading to bursting behavior. The model is able to
      produce almost all the classes of bursting predicted for systems with a planar
      fast subsystem. Transitions between classes can be obtained through an ultra-slow
      modulation of the model's parameters. A detailed exploration of the parameter
      space allows predicting possible transitions. This provides a single framework to
      understand the coexistence of diverse bursting patterns in physical and
      biological systems or in models.

PMID- 28744736
TI  - Management of bone health in postmenopausal women on aromatase inhibitors (AIs):
      a single health care system experience.
AB  - INTRODUCTION: Aromatase inhibitors (AIs) are the preferred therapy for
      postmenopausal women with early-stage estrogen receptor-positive breast cancers.
      However, their use causes bone loss and increased risks of osteoporosis and
      fractures. METHODS: This is a retrospective review of all postmenopausal women
      with breast cancer diagnosed and treated with AI between 2010 and 2015. Of the
      564 women identified, 319 were eligible. RESULTS: The median age at AI initiation
      was 65 years (range 51-85 years), and the median duration of AI therapy was 28
      months (1-72 months). The median number of DEXA scans per woman was 1 (0-4),
      performed at a median frequency of 24 months (1-48 months). Recommendations for
      calcium and vitamin D were in 66 and 59% of women, respectively. There were 52
      (16%) women who received antiresorptive treatments with bisphosphonates (69%),
      denosumab (25%), or both drugs (6%). Based on guideline recommendations from six
      societies, starting antiresorptive treatment was unnecessary in 15-54% of women.
      CONCLUSIONS: In this single health system experience, women start antiresorptive
      drugs that are unnecessary in 15-52%. These results highlight the nonuniformity
      in guideline recommendations, and this has implications for quality of care, cost
      effectiveness, and value-of-care analyses for preventing fractures.

PMID- 28744738
TI  - Reply to "Comment to Sparrelid, E. et al. Dynamic Evaluation of Liver Volume and
      Function in Associating Liver Partition and Portal Vein Ligation for Staged
      Hepatectomy. Journal of Gastrointestinal Surgery (2017)".

PMID- 28744737
TI  - Neuroendocrine Liver Metastasis: Prognostic Implications of Primary Tumor Site on
      Patients Undergoing Curative Intent Liver Surgery.
AB  - BACKGROUND: Neuroendocrine tumors typically arise from pancreatic (PNET) vs.
      gastrointestinal or thoracic origins (non-PNET). The impact of primary tumor site
      on long-term prognosis following resection of neuroendocrine liver metastasis
      (NELM) remains poorly defined. The objective of the current study was to define
      the association of primary tumor location on prognosis of patients undergoing
      curative intent liver resection for NELM. METHODS: Between 1990 and 2014, 421
      patients who underwent resection of NELM were identified from a multi
      institutional database. Clinicopathological characteristics, operative details,
      and outcomes were stratified and analyzed by location of the primary tumor (PNET
      vs. non-PNET). A propensity score-matched analysis was utilized to assess the
      impact of primary tumor location on long-term survival. RESULTS: Among the 421
      patients, 197 (46.8%) patients had NELM from a PNET primary while 224 (53.2%) had
      a non-PNET primary (small bowel, n = 145; rectal, n = 10; bronchial, n = 22;
      other, n = 47). There were no differences in tumor burden and tumor site, while
      presence of extrahepatic disease was more common among patients with non-PNET
      NELM (extrahepatic disease, PNET NELM, n = 11 27.5% vs. non-PNET NELM, n = 29
      72.5%; p = 0.010). Patients with PNET NELM were more likely to have non
      functional disease compared with patients who had non-PNET NELM (non-functional,
      PNET NELM, n = 117 54.9% vs. non-PNET NELM, n = 96 45.1%; p = 0.011). On the
      final pathological specimen of the resected NELM, patients with PNET NELM were
      more likely to have a moderately differentiated tumor (59.3%), while patients
      with non-PNET NELM were more likely to have a poorly differentiated tumor (67.8%)
      (p = 0.005). Patients with PNET NELM had a worse 5-year DFS and 5-year OS
      compared with patients who had non-PNET NELM (DFS, PNET 36.2% vs. non-PNET 55.2%;
      p = 0.001 and OS, PNET 79.5% vs. non-PNET 83.4%; p = 0.008). After propensity
      score matching, both 5-year DFS and 5-year OS of the PNET and non-PNET groups
      were comparable (DFS, PNET 46.2% vs. non-PNET 55.9%; p = 0.22 and OS, PNET 81.5%
      vs. non-PNET 84.3%; p = 0.19). CONCLUSION: PNET patients more often present with
      non-functional NELM and moderately differentiated tumors. On propensity-matched
      analysis, factors such as extrahepatic disease and tumor grade, but not primary
      tumor location, were associated with prognosis of patients undergoing curative
      intent liver surgery for NELM.

PMID- 28744739
TI  - Perforated Meckel's Diverticulitis.
AB  - A Meckel's diverticulum is a vestigial remnant present in approximately 2% of the
      population. Fewer than 10% of patients with a Meckel's diverticulum develop
      clinical complications, and such findings are exceedingly rare in the geriatric
      population. We present a case of perforated Meckel's diverticulitis with a
      fistulous tract involving the anterior abdominal wall in an 85-year-old male.

PMID- 28744740
TI  - Acute Cholangitis After Bilioenteric Anastomosis for Bile Duct Injuries.
AB  - BACKGROUND/PURPOSE: The study aims to describe the clinical features,
      microbiology, and associated factors of acute cholangitis (AC) after bilioenteric
      anastomosis (BEA) for biliary duct injury (BDI). Additionally, we assessed the
      performance of the Tokyo Guidelines 2013 (TG13) recommendations in these
      patients. METHODS: We conducted a case-control study of 524 adults with a history
      of BEA for BDI from January 2000 to January 2014. A propensity score adjustment
      was performed for the analysis of the independent role of the main factors
      identified during the univariate logistic regression procedure. RESULTS: We
      identified 117 episodes of AC in 70 patients; 51.3% were definitive AC according
      to the TG13 diagnostic criteria, and 39.3% did not fulfill the imaging criteria
      of AC. A history of post-operative biliary complications (OR 2.55, 95% CI 1.38
      4.70) and the bile duct confluence preservation (OR 0.46, 95% CI 0.24-0.87) were
      associated with AC. Eighty-nine percent of the microorganisms were
      Enterobacteriaceae; of them, 28% were extended spectrum beta-lactamase (ESBL)
      producers. CONCLUSIONS: AC is a common complication after BEA and must be
      suspected even in the absence of imaging findings, particulary in patients with a
      history of post-operative biliary complications, and/or without bile duct
      confluence preserved. An empirical treatment for ESBL-producing
      Enterobacteriaceae may be appropriate in patients living in countries with a high
      rate of bacterial drug resistance.

PMID- 28744741
TI  - Perioperative and Long-Term Outcome for Intrahepatic Cholangiocarcinoma: Impact
      of Major Versus Minor Hepatectomy.
AB  - BACKGROUND: The objective of the current study was to investigate both short- and
      long-term outcomes of patients undergoing curative-intent resection for
      intrahepatic cholangiocarcinoma (ICC) stratified by extent of hepatic resection
      relative to overall final pathological margin status. METHODS: One thousand
      twenty-three patients with ICC who underwent curative-intent resection were
      identified from a multi-institutional database. Demographic, clinicopathological,
      and operative data, as well as overall (OS) and recurrence-free survival (RFS)
      were compared among patients undergoing major and minor resection before and
      after propensity score matching. RESULTS: Overall, 608 (59.4%) patients underwent
      major hepatectomy, while 415 (40.6%) had a minor resection. Major hepatectomy was
      more frequently performed among patients who had large, multiple, and bilobar
      tumors. Roughly half of patients (n = 294, 48.4%) developed a postoperative
      complication following major hepatectomy versus only one fourth of patients (n =
      113, 27.2%) after minor resection (p < 0.001). In the propensity model, patients
      who underwent major hepatectomy had an equivalent OS and RFS versus patients who
      had a minor hepatectomy (median OS, 38 vs. 37 months, p = 0.556; and median RFS,
      20 vs. 18 months, p = 0.635). Patients undergoing major resection had comparable
      OS and RFS with wide surgical margin (>=10 and 5-9 mm), but improved RFS when
      surgical margin was narrow (1-4 mm) versus minor resection in the propensity
      model. In the Cox regression model, tumor characteristics and surgical margin
      were independently associated with long-term outcome. CONCLUSIONS: Major
      hepatectomy for ICC was not associated with an overall survival benefit, yet was
      associated with increased perioperative morbidity. Margin width, rather than the
      extent of resection, affected long-term outcomes. Radical parenchymal-sparing
      resection should be advocated if a margin clearance of >=5 mm can be achieved.

PMID- 28744742
TI  - The Primary Result of Prospective Randomized Multicenter Trial of New Spray-Type
      Bio-absorbable Adhesion Barrier System (TCD-11091) Against Postoperative Adhesion
      Formation.
AB  - BACKGROUND: Postoperative adhesions are the major cause of postoperative
      complications including intestinal obstruction, infertility, and chronic pelvic
      pain. In order to reduce postoperative adhesions, Terumo Corporation (Tokyo,
      Japan) has developed an adhesion barrier system (TCD-11091) which is easy to use
      at the treatment site in various surgical procedures including laparoscopic
      surgeries. We conducted a prospective randomized single-blind study in patients
      who underwent laparotomy with ileostomy. METHODS AND RESULTS: One hundred twenty
      six patients were randomly assigned to TCD-11091 group (n = 62) or non-treatment
      group (n = 62). Patient backgrounds were similar between the groups. At the time
      of ileostomy closure (the second-look surgery), the observation was performed on
      55 in the TCD-11091 group and 43 in the control group. The incidence of adhesions
      observed at the second-look surgery was significantly lower in the TCD-11091
      group (52.7 versus 90.7%; p < 0.001). For the secondary endpoints, the incidence
      of wide extent adhesions (grade 2 or higher) was significantly reduced (38.2
      versus 79.1%; p < 0.001). Regarding the severity of adhesions, the incidence of
      grade 2 or higher adhesions was also significantly lower in the TCD-11091 group
      (47.3 versus 88.4%; p < 0.001). No differences in the incidence of adverse events
      were found between the TCD-11091 group and the non-treatment group (85.2 versus
      75.4%; p = 0.225). CONCLUSIONS: Use of TCD-11091 was safe and associated with
      significantly lower incidence of adhesion and severity of adhesions compared with
      non-treatment procedure.

PMID- 28744743
TI  - The Impact of Surgeon Volume on Outcomes After Pancreaticoduodenectomy: a Meta
      analysis.
AB  - BACKGROUND: Despite significant improvement in operative mortality rates
      following pancreaticoduodenectomy (PD), morbidity remains high. Outcomes
      following PD may be improved in high-volume centers and with high-volume
      surgeons. We sought to evaluate the association between surgeon experience and
      postoperative outcomes after PD. METHODS: An online database search of MEDLINE
      and EMBASE was performed; key bibliographies were reviewed. Studies comparing
      operative outcomes of high-volume surgeon (HVS) and low-volume surgeon (LVS)
      performing PD were included. Odds ratios with the corresponding 95% confidence
      intervals (CI) by random fixed effects models of pooled data were calculated.
      Definition of HVS varied among the studies, ranging from 6 to >20 PD/year. The
      primary endpoint was 30-day mortality, and secondary outcomes were complication
      rates, length of stay (LOS), hospital costs, and readmission rates. Study quality
      was assessed using STROBE (Strengthening the Reporting of Observational Studies
      in Epidemiology) criteria. RESULTS: Search strategy yielded 360 publications.
      Eleven studies met the inclusion criteria comprising 36,449 patients. Among these
      patients, 12,512 (34.3%) PDs were performed by HVS and 23,937 (65.7%) by LVS.
      Meta-analysis of included studies showed that HVS had significantly lower
      mortality rates than LVS (2.4 vs. 6.7%, OR 2.88; 95% CI 2.51-3.27, p < 0.001).
      They also had significantly lower overall complication rates (36.3 vs. 50.3%, OR
      1.71; 95% CI 1.62-1.81, p < 0.001), hospital costs (range $10,818-141,322 vs.
      $12,114-198,678, OR 0.13; 95% CI 0.07-0.19, p < 0.001), and LOS (range 11-35 vs.
      14-38 days, OR 2.86; 95% CI 2.03-3.68, p < 0.001). CONCLUSIONS: HVS performing PD
      have significantly better outcomes than LVS in terms of decreased mortality,
      morbidity, LOS, and hospital costs. Efforts toward increased regionalization of
      care should be discussed. Consensus regarding definition of HVS needs to be
      undertaken.

PMID- 28744744
TI  - The Effect of Neoadjuvant Chemoradiation on Anastomotic Leak and Additional 30
      Day Morbidity and Mortality in Patients Undergoing Total Gastrectomy for Gastric
      Cancer.
AB  - INTRODUCTION: In addition to increased perioperative morbidity, anastomotic leak
      following gastric resection for gastric cancer can have detrimental effects on
      overall and disease-free survival. The risk of anastomotic leak following
      neoadjuvant therapy remains unknown. The purpose of this study is to investigate
      the association of preoperative chemotherapy and radiation therapy with
      postoperative anastomotic leak and additional 30-day morbidity and mortality
      outcomes following total gastrectomy with reconstruction for gastric cancer using
      the American College of Surgeons National Surgical Quality Improvement Program
      (ACS-NSQIP). METHODS: Patients who underwent total gastrectomy with
      reconstruction for gastric cancer from 2005 to 2012 were identified. Within the
      NSQIP database, anastomotic leak is captured as an organ space infection. The
      association of preoperative chemotherapy and radiation therapy with anastomotic
      leak and additional 30-day morbidity and mortality outcomes was investigated
      using chi-squared analysis, Fisher's exact test, and Student's t test. RESULTS: A
      total of 1135 patients met inclusion criteria; 121 (10.7%) patients underwent
      preoperative chemotherapy within 30 days of surgery, and 53 (4.7%) patients
      underwent preoperative radiation therapy within 90 days of surgery. Neither
      preoperative chemotherapy nor radiation therapy was associated with an increased
      risk of anastomotic leak (p = 0.12 and p = 0.58, respectively). When compared to
      patients who did not undergo neoadjuvant therapy, patients who underwent either
      preoperative chemotherapy or radiation therapy did not experience a higher
      frequency of 30-day mortality (p = 0.41), cardiac (p = 0.49), wound (p = 0.76),
      renal (p = 0.13), septic (p = 0.55), or venous thromboembolism (p = 0.19) events
      and were significantly less likely to experience a pulmonary event (p = 0.02).
      CONCLUSION: Neoadjuvant therapy prior to gastric resection for gastric cancer is
      not associated with an increased risk of anastomotic leak or other additional
      short-term morbidity or mortality.

PMID- 28744745
TI  - Circulating mRNA in Maternal Plasma at the Second Trimester of Pregnancy: A
      Possible Screening Tool for Cardiac Conotruncal and Left Ventricular Outflow
      Tract Abnormalities.
AB  - OBJECTIVE: Maternal plasma is a source of circulating placental nucleic acids.
      This study was designed to detect aberrantly expressed placental mRNA genes
      circulating in the maternal plasma of pregnancies affected with fetal conotruncal
      anomalies (CNTRA) and left-ventricular outflow tract (LVOT) obstruction in the
      second trimester of pregnancy. METHODS: This was a retrospective monocentric
      study conducted from 1 Jan 2016 to 31 Dec 2016. NanoString technology was used to
      identify aberrantly expressed genes, comparing 36 women carrying a fetus with
      CNTRA or LVOT obstruction to 42 controls at 19-24 weeks of gestation. The genes
      with differential expression were subsequently tested using real-time polymerase
      chain reaction. Linear discriminant analysis was used to combine all the mRNA
      species with discriminant ability for CNTRA and LVOT obstruction. A multivariable
      receiver operating characteristic (ROC) curve having the estimated discriminant
      score as an explanatory variable was generated for the two affected groups versus
      controls. RESULTS: Three genes with differential expression, namely MAPK1, IQGAP1
      and Visfatin were found. The ROC curves yielded detection rates of 60 and 62.5%
      at a false-positive rate of 5% for CNTRA and LVOT, respectively. CONCLUSIONS:
      These data suggested that molecular screening of CNTRA and LVOT obstruction in
      the second trimester is feasible. Prospective studies are needed to test the
      discriminant ability of these genes and to calculate the predictive positive
      value in the general population.

PMID- 28744746
TI  - A computational study of ANTA and NTO derivatives.
AB  - This work is a study of 5-amino-3-nitro-1,2,4-triazole (ANTA), 3-nitro-1,2,4
      triazol-5-one (NTO), and nitrated derivatives of ANTA and NTO. RDX and TNT were
      studied for comparison. ANTA and NTO are low-sensitive high explosives with
      detonation properties comparable to 2,4,6-trinitrotoluene (TNT) and 1,3,5
      trinitroperhydro-1,3,5-triazine (RDX). We showed previously that nitrated NTO and
      ANTA compounds, when used in a glycidyl azide polymer (GAP) matrix in rocket
      propellants, could give impulses above 2600 m/s and that the oxygen balance is
      positive. If used in aluminized explosives, the heat of detonation may be
      increased to a practical level significantly above RDX/aluminum compositions.
      Here, we use two different methods for sensitivity and two density functional
      theory functionals, B3LYP and M06-2X with the 6-31G(d) basis set, together with
      the complete basis set method CBS-4M. Calculations indicate that most of the
      nitrated derivatives have nearly equal sensitivity to RDX. Significantly
      different bond dissociation energies in the nitrimino functional group are
      predicted, although most models give much the same result.

PMID- 28744747
TI  - Structural and inhibition analysis of novel sulfur-rich 2-mercaptobenzothiazole
      and 1,2,3-triazole ligands against Mycobacterium tuberculosis DprE1 enzyme.
AB  - Mycobacterium tuberculosis decaprenylphosphoryl-beta-D-ribose oxidase (MtbDprE1)
      acts in concert with decaprenylphosphoryl-beta-D-ribose 2-epimerase (MtbDprE2)
      and catalyzes the epimerization of DPR into DPA. DPA is the sole precursor for
      synthesis of arabinogalactan and lipoarabinomannan in the mycobacterial cell
      wall. MtbDprE1 is a unique antimalarial drug target and many covalent and non
      covalent inhibitors against MtbDprE1 have been studied for their antituberculosis
      activities. In the current study, we have purified MtbDprE1 enzyme and
      synthesized six sulfur-rich 2-mercaptobenzothiazole and 1, 2, 3-triazole
      conjugated ligands and performed binding analysis with MtbDprE1. All ligands have
      shown competitive binding, as observed for other covalently and noncovalently
      bound MtbDprE1 inhibitors. Molecular docking analysis of six ligands with
      MtbDprE1 shows that they occupy the substrate binding pocket of MtbDprE1 and are
      stabilized by hydrogen bonds and van der Waals interactions. Our study shows that
      sulfur-rich 2-mercaptobenzothiazole ligands act as specific inhibitors against
      MtbDprE1 and could be used as antituberculosis agents.

PMID- 28744748
TI  - Biliary complications after living donor liver transplantation: A retrospective
      analysis of the Kyoto experience 1999-2004.
AB  - BACKGROUND AND AIM: In living donor liver transplantation (LDLT), biliary
      complications continue to be the most frequent cause of morbidity and may
      contribute to mortality of recipients although there are advances in surgical
      techniques. This study will evaluate retrospectively the short-term and long-term
      management of biliary complications. METHODS: During the period from May 1999, to
      May 2004, 505 patients underwent 518 LDLT in the Department of Liver
      Transplantation and Immunology, Kyoto University Hospital, Japan. The data was
      collected and analyzed retrospectively. RESULTS: The recipients were 261 males
      (50.4%) and 257 females (49.6%). Biliary complications were reported in 202/518
      patients (39.0%), included; biliary leakage in 79/518 (15.4%) patients, leakage
      followed by biloma in 13/518 (2.5%) patients, leakage followed by stricture in
      9/518 (1.8%) patients, and biliary strictures in 101/518 (19.3%) patients. Proper
      management of the biliary complications resulted in a significant (p value 0.002)
      success rate of 96.5% compared to the failure rate which was 3.5%. CONCLUSION:
      Careful preoperative evaluation and the proper intraoperative techniques in
      biliary reconstruction decrease biliary complications. Early diagnosis and proper
      management of biliary complications can decrease their effect on both the patient
      and the graft survival over the long period of follow up.

PMID- 28744749
TI  - A functional BRCA1 coding sequence genetic variant contributes to prognosis of
      triple-negative breast cancer, especially after radiotherapy.
AB  - PURPOSE: As a subtype of breast cancer, triple-negative breast cancer (TNBC)
      shows poor prognosis and high heterogeneity. Precise identification of TNBC
      subgroups relevant to clinical prognosis is crucial in the design and
      administration of individualized treatments. This study aimed to evaluate the
      prognostic value of the functional BRCA1 rs799917 genetic variant in TNBC.
      METHODS: Associations between the rs799917 polymorphism and progression risk were
      investigated after genotyping 370 TNBC patients. Hazard ratios (HRs) and 95%
      confidence intervals (CIs) were estimated by Cox regression.  RESULTS: We found
      that the rs799917T allele was associated with a significantly increased risk of
      disease progression and shortened progression-free survival time (PFS) (P = 0.001
      for log-rank test). Notably, TNBC patients with the rs799917 CC genotype showed
      about 22 months prolonged PFS compared to the TT genotype after radiotherapy (HR
      4.44, 95% CI 1.98-9.93; P = 2.9 * 10-4). Additionally, in overweight patients,
      the mean PFS of the rs799917TT genotype was 10 months shorter than that of the CC
      genotype (HR 3.57, 95% CI 1.46-8.73, P = 0.005). CONCLUSIONS: Our findings
      demonstrate that the functional BRCA1 genetic variant contributes to prognosis of
      TNBC. Our study also highlights the clinical potential of this polymorphism in
      the screening of high-risk TNBC patients for recurrence and the possibility of
      patient-tailored decisions especially during radiotherapy.

PMID- 28744750
TI  - Comments on "Primary tumor location predicts the site of local relapse after
      nipple-areola complex (NAC) sparing mastectomy" by Cont et al. Breast Cancer Res
      Treat, 2017.

PMID- 28744751
TI  - Functional importance of PP2A regulatory subunit loss in breast cancer.
AB  - PURPOSE: Protein phosphatase 2A (PP2A) is a family of serine/threonine
      phosphatases that regulate multiple cellular signalling pathways involved in
      proliferation, survival and apoptosis. PP2A inhibition occurs in many cancers and
      is considered a tumour suppressor. Deletion/downregulation of PP2A genes has been
      observed in breast tumours, but the functional role of PP2A subunit loss in
      breast cancer has not been investigated. METHODS: PP2A subunit expression was
      examined by immunohistochemistry in human breast tumours, and by qPCR and
      immunoblotting in breast cancer cell lines. PP2A subunits were inhibited by
      shRNA, and mutant PP2A genes overexpressed, in MCF10A and MCF7 cells, and growth
      and signalling in standard and three-dimensional cultures were assessed. RESULTS:
      Expression of PP2A-Aalpha, PP2A-Balpha and PP2A-B'alpha subunits was
      significantly lower in primary human breast tumours and lymph node metastases,
      compared to normal mammary tissue. PP2A-Aalpha and the regulatory subunits PP2A
      Balpha, -Bdelta and -B'gamma were also reduced in breast cancer cell lines
      compared to normal mammary epithelial cells. Functionally, shRNA-mediated
      knockdown of PP2A-Balpha, -B'alpha and -B'gamma, but not PP2A-Aalpha, induced
      hyper-proliferation and large multilobular acini in MCF10A 3D cultures,
      characterised by activation of ERK. Expression of a breast cancer-associated PP2A
      A mutant, PP2A-Aalpha-E64G, which inhibits binding of regulatory subunits to the
      PP2A core, induced a similar hyper-proliferative phenotype. Knockdown of PP2A
      Balpha also induced hyper-proliferation in MCF7 breast cancer cells. CONCLUSION:
      These results suggest that loss of specific PP2A regulatory subunits is
      functionally important in breast tumourigenesis, and support strategies to
      enhance PP2A activity as a therapeutic approach in breast cancer.

PMID- 28744752
TI  - Radiotherapy for ductal carcinoma in situ and risk of second non-breast cancers.
AB  - PURPOSE: Radiotherapy for ductal carcinoma (DCIS) is increasing, but the risks
      and benefits of the treatment remain uncertain. We aimed to investigate the
      relationship between radiotherapy for DCIS and risk of second non-breast cancers
      in a large US cohort. METHODS: We conducted a retrospective cohort study of
      52,556 women in 12 U.S. population-based cancer registries diagnosed with first
      primary DCIS during 1992-2008 at age 25-79 years. We estimated relative risks
      (RRs), attributable risks (AR), and excess absolute risks (EAR) of second non
      breast cancers associated with radiotherapy using Poisson regression adjusted for
      age at year of diagnosis, grade, hormonal therapy (yes/no or unknown), and time
      since diagnosis. RESULTS: Approximately half of the women (46.3%) received
      radiotherapy. Radiotherapy was associated with an increased risk of all second
      non-breast cancers combined [RR 1.17, 95% confidence interval (CI) 1.08-1.28] and
      all in-field, radiation-related second cancers combined (RR 1.37, 95% CI 1.15
      1.63), driven by second lung cancers (RR 1.33, 95% CI 1.10-1.60) and non-CLL
      leukemia (RR 1.71, 95% CI 1.02-2.86). The estimated cumulative excess risk of all
      second non-breast cancers was 0.8% by 15 years after DCIS diagnosis. CONCLUSIONS:
      Radiotherapy was associated with an increased risk of second non-breast cancers.
      The specific excess of cancers at sites likely in/near the radiotherapy field
      suggests the findings are unlikely due exclusively to confounding, but further
      research into factors related to receipt of radiotherapy is needed. Our risk
      estimates can be used to help assess the balance of the risks and benefits of
      radiotherapy for DCIS and to inform clinical practice.

PMID- 28744753
TI  - Erratum to: Decreasing the Stigma of Mental Illness Through a Student-Nurse
      Mentoring Program: A Qualitative Study.

PMID- 28744754
TI  - Erratum to: Exogenous Adipokine Peptide Resistin Protects Against Focal Cerebral
      Ischemia/Reperfusion Injury in Mice.

PMID- 28744755
TI  - Resveratrol Protects Against Vacuous Chewing Movements Induced by Chronic
      Treatment with Fluphenazine.
AB  - Typical antipsychotics, which are commonly used to treat schizophrenia, cause
      motor disorders such as tardive dyskinesia (TD) in humans and orofacial
      dyskinesia (OD) in rodents. The disease mechanisms as well as treatment
      effectiveness are still unknown. In this study, we investigated the effect of
      resveratrol, a polyphenol with neuroprotective properties, on behavioral changes
      induced by chronic treatment with fluphenazine in rats and the possible
      relationship between monoamine oxidase (MAO) activity and vacuous chewing
      movements (VCMs). Rats were treated for 18 weeks with fluphenazine enantate [25
      mg/kg, intramuscularly (i.m.), every 21 days] and/or resveratrol (20 mg/kg,
      offered daily in drinking water). Next, body weight gain, behavioral parameters
      (VCMs and open field tests-locomotor and rearing activity), and MAO activity were
      evaluated. Fluphenazine treatment reduced body weight gain, number of crossings
      and rearings, and the co-treatment with resveratrol did not affect these
      alterations. Fluphenazine increased the prevalence and intensity of VCMs and the
      co-treatment with resveratrol reduced the VCMs. Furthermore, a negative
      correlation was found between the number of VCMs and MAO-B activity in the
      striatum of rats. Our data suggest that resveratrol could be promissory to
      decrease OD. Moreover, MAO-B activity in the striatum seems to be related to VCMs
      intensity.

PMID- 28744756
TI  - Short-term outcome of unicompartmental knee arthroplasty in the octogenarian
      population.
AB  - PURPOSE: Unicompartmental knee arthroplasty (UKA) provides significant benefits
      to patients with anteromedial osteoarthritis, with good long-term results.
      Morbidity and mortality rates are lower, and recovery is quicker. These benefits
      would be advantageous to the octogenarian population whom carry significant
      comorbidities. The primary aim was to compare the short-term functional outcome
      at 2 years of UKA in the octogenarian population against a stratified younger
      cohort of patients. We hypothesised that the octogenarian population would have
      equally significant improved patient-reported outcome measures. METHODS:
      Prospective patient-reported outcome measures, including Oxford Knee Score (OKS),
      satisfaction rates and Euro-Quol (EQ-5D) scores at 1-year and 2-year post
      operative data, were collected and analysed. Three hundred and ninety-five medial
      Oxford Phase 3 UKA implants were evaluated. Mean follow-up was 4.7 years (range
      2.1-7.7). Secondary outcomes including revision rates, length of stay,
      complications and mortality were recorded. Our patient population was stratified
      into three cohort groups based on age: 60-69, 70-79 and 80-89 years. RESULTS: The
      OKS and EQ-5D score improved significantly in all three groups at all post
      operative time periods and maintained at 2 years. The OKS at 2 years post
      operatively by age was 39.5 (SD 18.6), 39.2 (SD 17.7) and 39.3 (SD 15.9),
      respectively. No significant difference of implant survival was found between the
      groups. The overall revision rate was 28/395 (7%). The 90-day mortality in the
      present series was one patient. CONCLUSION: The 2-year short-term functional
      outcome, revision rates and satisfaction of UKA in the octogenarian population
      did not differ statistically from other age groups. LEVEL OF EVIDENCE: III.

PMID- 28744757
TI  - Six-implant-supported immediate fixed rehabilitation of atrophic edentulous
      maxillae with tilted distal implants.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate the treatment
      outcome of six Bredent blueSkyTM implants (Bredent GmbH, Senden, Germany)
      immediately loaded with a fixed full-arch prosthesis (two tilted posterior and
      four axial frontal and premolar implants). METHODS: All 10 patients with atrophic
      edentulous maxillae being treated with a standardized procedure from 09/2009 to
      01/2013, who had a follow-up of at least 3 years, were included. Sixty implants
      were placed to support 10 screwed prostheses. Twenty-one of them were inserted in
      fresh extraction sockets. Lab-side-prepared provisional fixed prostheses were
      placed at the day of implantation. Periotest (PT) values and implant stability
      quotient (ISQ) were measured after implant surgery and after 3 months of healing
      in all patients. RESULTS: The analyzed implants were in function in mean 64 +/-
      13 months (range 42 to 84 months). One axial and two tilted implants failed in
      three patients. The mean PT values decreased, and ISQ increased significantly
      after the first 3 months at the osseointegrated tilted and axial implants. With
      an area under the curve of 0.503 and 0.506 in the receiver operating
      characteristic, the PT values and the ISQ were unspecific parameters and
      unsuitable as a predictor for the risk of non-osseointegration. CONCLUSIONS:
      Within the limits of this small group (n = 10 patients/60 implants), the failure
      rate of the analyzed implant system (n = 3 respective 5% implant loss) seems to
      be comparable with other immediate-loading protocols. The failure rate of tilted
      implants in the atrophic upper jaw was quite high, but the aimed treatment
      concept could be achieved in every patient. The rehabilitation of the posterior
      region in edentulous maxilla remains a challenge.

PMID- 28744758
TI  - Gitelman syndrome: an analysis of the underlying pathophysiologic mechanisms of
      acid-base and electrolyte abnormalities.
AB  - Gitelman syndrome is the most common inherited tubular disease resulting from
      mutations of the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride
      cotransporter in the early distal convoluted tubules. The review presents the
      underlying pathophysiologic mechanisms of acid-base and electrolyte abnormalities
      observed in patients with Gitelman syndrome. The syndrome is usually
      characterized by hypokalemic metabolic alkalosis in combination with
      hypomagnesemia and hypocalciuria. Additionally, increased chloride excretion and
      renin/aldosterone levels, hypophosphatemia (occasionally), hyponatremia (rarely)
      and glucose intolerance/insulin resistance have been reported. The knowledge of
      the pathophysiologic mechanisms is useful for the treatment of patients with
      Gitelman syndrome as well as for the understanding of other tubular diseases.

PMID- 28744759
TI  - Do Verbal Children with Autism Comprehend Gesture as Readily as Typically
      Developing Children?
AB  - Gesture comprehension remains understudied, particularly in children with autism
      spectrum disorder (ASD) who have difficulties in gesture production. Using a
      novel gesture comprehension task, Study 1 examined how 2- to 4-year-old typically
      developing (TD) children comprehend types of gestures and gesture-speech
      combinations, and showed better comprehension of deictic gestures and reinforcing
      gesture-speech combinations than iconic/conventional gestures and supplementary
      gesture-speech combinations at each age. Study 2 compared verbal children with
      ASD to TD children, comparable in receptive language ability, and showed similar
      patterns of comprehension in each group. Our results suggest that children
      comprehend deictic gestures and reinforcing gesture-speech combinations better
      than iconic/conventional gestures and supplementary combinations-a pattern that
      remains robust across different ages within TD children and children with ASD.

PMID- 28744760
TI  - Development and Psychometric Evaluation of the Autism Stigma and Knowledge
      Questionnaire (ASK-Q).
AB  - ASD knowledge deficits contribute to disparities in the timing and quality of ASD
      services. To address the limitations with existing measures of ASD knowledge, we
      developed and examined the Autism Stigma and Knowledge Questionnaire (ASK-Q),
      which comprehensively assesses multiple subdomains of ASD knowledge while
      maintaining strong psychometric support and cross-cultural utility. ASK-Q items
      derived from the published research are organized into four subscales: (i)
      diagnosis, (ii) etiology, (iii) treatment, and (iv) stigma. ASK-Q items were
      selected based on ratings of face, construct, and cross-cultural validity by a
      group of 16 international researchers. Using Diagnostic Classification Modeling
      we confirmed the proposed factor structure and evaluated the statistical validity
      of each item among a lay sample of 617 participants.

PMID- 28744761
TI  - Olfactory Processing in Male Children with Autism: Atypical Odor Threshold and
      Identification.
AB  - Sensory issues are of great interest in ASD diagnosis. However, their
      investigation is mainly based on external observation (parent reports), with
      methodological limitations. Unobtrusive olfactory assessment allows studying
      autism neurosensoriality. Here, 20 male children with high-functioning ASD and 20
      matched controls were administered a complete olfactory test battery, assessing
      olfactory threshold, identification and discrimination. ASD children show lower
      sensitivity (p = 0.041), lower identification (p = 0.014), and intact odor
      discrimination (p = 0.199) than controls. Comparing olfactory and clinical
      scores, a significant correlation was found in ASD between olfactory threshold
      and the CBCL social problems (p = 0.011) and aggressive behavior (p = 0.012) sub
      scales. The pattern featuring peripheral hyposensitivity, high-order difficulties
      in odor identification and regular subcortical odor discrimination is discussed
      in light of hypo-priors hypothesis for autism.

PMID- 28744762
TI  - Mortality after primary intracerebral hemorrhage in relation to post-stroke
      seizures.
AB  - Seizures after intracerebral hemorrhage are repeatedly seen. Whether the
      development of seizures after intracerebral hemorrhage affects survival in the
      long term is unknown. This study aims to determine the relation between seizures
      (i.e., with and without anti-epileptic therapy) and long-term mortality risk in a
      large patient population with intracerebral hemorrhage. We retrospectively
      included patients with a non-traumatic ICH in all three hospitals in the South
      Limburg region in the Netherlands between January 1st 2004 and December 31st
      2009, and we assessed all-cause mortality until March 14th 2016. Patient who did
      not survive the first seven days after intracerebral hemorrhage were excluded
      from analyses. We used Cox multivariate analyses to determine independent
      predictors of mortality. Of 1214 patients, 783 hemorrhagic stroke patients
      fulfilled the inclusion criteria, amongst whom 37 (4.7%) patients developed early
      seizures (within 7 days after hemorrhage) and 77 (9.8%) developed late seizures
      (more than 7 days after hemorrhage). Seizure development was not significantly
      related to mortality risk after correction for conventional vascular risk factors
      and hemorrhage severity. However, we found a small but independent relation
      between the use of anti-epileptic drugs and a lower long-term mortality (HR =
      0.32, 95% CI 0.11-0.91). In our large population, seizures and epilepsy did not
      relate independently to an increased mortality risk after hemorrhage.

PMID- 28744763
TI  - A case of colonic stenosis caused by cold snare polypectomy for the removal of a
      colonic polyp.
AB  - A 78-year-old woman with hypertension had a positive fecal immunochemical test
      and underwent colonoscopy, which revealed a 4 mm sessile polyp (Paris type; 0-Is)
      in the transverse colon. Based on low magnification colonoscopy with narrow band
      imaging, the polyp was Type 2 according to the NBI International Colorectal
      Endoscopic classification, diagnosed as an adenoma, and then resected via cold
      snare polypectomy (CSP). Five days after CSP, she complained of right-sided
      abdominal pain. Abdominal CT showed focal wall thickening of the transverse colon
      and focal infiltration of tissues surrounding the transverse colon. The
      inflammatory lesion was considered to coincide with the location of the polyp
      resected with CSP. However, no inflammatory findings were seen in other parts of
      the colon, and intraperitoneal free air and ascites were not identified.
      Moreover, no inflammatory findings and no infectious signs in other organs were
      present. She was administered intravenous antibiotics and, 19 days later, she was
      discharged from our hospital. Approximately 3 months later, colonoscopy revealed
      colonic stenosis associated with red mucosa and ulceration in the transverse
      colon where the polyp had been resected with CSP. Contrast-enhanced X-ray
      revealed an approximately 1 cm-long colonic stenosis in the transverse colon near
      the hepatic flexure.

PMID- 28744764
TI  - The Miracle Baby Grows Up: Hypoplastic Left Heart Syndrome in the Adult.
AB  - PURPOSE OF REVIEW: Hypoplastic left heart syndrome (HLHS) is characterized by
      underdevelopment of the mitral valve, left ventricle, and aorta and is ultimately
      palliated with a single-ventricle repair. Universally fatal in infancy prior to
      the advent of modern surgical techniques, the majority of HLHS patients will now
      reach adulthood. However, despite improvements in early survival, the HLHS
      population continues to face significant morbidity and early mortality. This
      review delineates common sources of patient morbidity and highlights areas in
      need of additional research for this growing segment of the adult congenital
      heart disease population. RECENT FINDINGS: It has become increasingly clear that
      palliated adult single ventricle patients, like those with HLHS, face significant
      life-long morbidity from elevated systemic venous pressures as a consequence of
      the Fontan procedure. Downstream organ dysfunction secondary to elevated Fontan
      pressures has the potential to significantly impact long-term management
      decisions, including strategies of organ allocation. Because of the presence of a
      morphologic systemic right ventricle, HLHS patients may be at even higher risk
      than other adult patients with a Fontan. Because the adult HLHS population
      continues to grow, recognition of common sources of patient morbidity and
      mortality is becoming increasingly important. A coordinated effort between
      patients and providers is necessary to address the many remaining areas of
      clinical uncertainty to help ensure continued improvement in patient prognosis
      and quality of life.

PMID- 28744765
TI  - Participant Nonnaivete and the reproducibility of cognitive psychology.
AB  - Many argue that there is a reproducibility crisis in psychology. We investigated
      nine well-known effects from the cognitive psychology literature-three each from
      the domains of perception/action, memory, and language, respectively-and found
      that they are highly reproducible. Not only can they be reproduced in online
      environments, but they also can be reproduced with nonnaive participants with no
      reduction of effect size. Apparently, some cognitive tasks are so constraining
      that they encapsulate behavior from external influences, such as testing
      situation and prior recent experience with the experiment to yield highly robust
      effects.

PMID- 28744766
TI  - A meta-analysis of the survival-processing advantage in memory.
AB  - The survival-processing advantage occurs when processing words for their survival
      value improves later performance on a memory test. Due to the interest in this
      topic, we conducted a meta-analysis to review the literature regarding the
      survival-processing advantage, in order to estimate a bias-corrected effect size.
      Traditional meta-analytic methods were used, as well as the test of excess
      significance, p-curve, p-uniform, trim and fill, PET-PEESE, and selection models,
      to reevaluate previous effect sizes while controlling for forms of small-study
      size effects. The average effect sizes for survival processing ranged between eta
      p2 = .06 and .09 for between-subjects experiments and between eta p2 = .15 and
      .18 for within-subjects experiments, after correcting for potential bias and
      selective reporting. Overall, researchers can expect to find medium to large
      survival-processing effects, with selective reporting and bias-correcting
      techniques typically estimating lower effect sizes than traditional meta-analytic
      techniques.

PMID- 28744767
TI  - Mind, rationality, and cognition: An interdisciplinary debate.

PMID- 28744768
TI  - Causal learning is collaborative: Examining explanation and exploration in social
      contexts.
AB  - Causal learning in childhood is a dynamic and collaborative process of
      explanation and exploration within complex physical and social environments.
      Understanding how children learn causal knowledge requires examining how they
      update beliefs about the world given novel information and studying the processes
      by which children learn in collaboration with caregivers, educators, and peers.
      The objective of this article is to review evidence for how children learn causal
      knowledge by explaining and exploring in collaboration with others. We review
      three examples of causal learning in social contexts, which elucidate how
      interaction with others influences causal learning. First, we consider children's
      explanation-seeking behaviors in the form of "why" questions. Second, we examine
      parents' elaboration of meaning about causal relations. Finally, we consider
      parents' interactive styles with children during free play, which constrains how
      children explore. We propose that the best way to understand children's causal
      learning in social context is to combine results from laboratory and natural
      interactive informal learning environments.

PMID- 28744769
TI  - Association Between Candiduria and Candidemia: A Clinical and Molecular Analysis
      of Cases.
AB  - The risk of developing candidemia after candiduria is reportedly very low, but it
      has not been adequately investigated. The aim of this study was to examine the
      molecular relatedness between Candida strains isolated from adult patients with
      candidemia and concomitant candiduria in association with the clinical
      characteristics of the cases. All episodes of candidemia occurring in a tertiary
      care academic hospital during a 5-year period were recorded prospectively.
      Patients with episodes of candiduria occurring two weeks preceding to or one week
      following a positive for Candida blood culture were included in the study. The
      genotypic relatedness of Candida strains isolated from blood and urine was
      investigated by pulsed-field gel electrophoresis after digestion with the BssHII
      restriction endonuclease. We recorded 141 candidemia episodes, occurring in 134
      patients. Twelve episodes of candidemia with concomitant candiduria occurred in
      11 patients (8% of all candidemias). In six of these episodes, the strains in the
      blood-urine pairs belonged to different species. In two episodes, the isolates
      belonged to the same species but were not genetically related, and only in four
      (2.8% of all candidemias), the strains were related. All four patients were
      severely ill and had multiple risk factors for candidemia. These findings
      indicate that in hospitalized patients with candidemia, concomitant candiduria is
      rare and usually an independent event, confirming previous reports. In the
      critically ill, however, the existence of genetically related strains in blood
      and urine appears to be more frequent, with more probable the hematogenous
      dissemination.

PMID- 28744770
TI  - The Evolution of Electrospray Generated Droplets is Not Affected by Ionization
      Mode.
AB  - Ionization efficiency and mechanism in ESI is strongly affected by the properties
      of mobile phase. The use of mobile-phase properties to accurately describe
      droplets in ESI source is convenient but may be inadequate as the composition of
      the droplets is changing in the plume due to electrochemical reactions occurring
      in the needle tip as well as continuous drying and fission of droplets.
      Presently, there is paucity of research on the effect of the polarity of the ESI
      mode on mobile phase composition in the droplets. In this paper, the change in
      the organic solvent content, pH, and droplet size are studied in the ESI plume in
      both ESI+ and ESI- ionization mode. We introduce a rigorous way - the absolute pH
      (pHabsH2O) - to describe pH change in the plume that takes into account organic
      solvent content in the mobile phase. pHabsH2O enables comparing acidities of ESI
      droplets with different organic solvent contents. The results are surprisingly
      similar for both ionization modes, indicating that the dynamics of the change of
      mobile-phase properties is independent from the ESI mode used. This allows us to
      conclude that the evolution of ESI droplets first of all proceeds via the
      evaporation of the organic modifier and to a lesser extent via fission of smaller
      droplets from parent droplets. Secondly, our study shows that qualitative
      findings related to the ESI process obtained on the ESI+ mode can almost directly
      be applied also in the ESI- mode. Graphical Abstract ?.

PMID- 28744771
TI  - Anti-Inflammatory Effects of Stearidonic Acid Mediated by Suppression of NF
      kappaB and MAP-Kinase Pathways in Macrophages.
AB  - Stearidonic acid (SDA, 18:4n-3) is an omega-3 polyunsaturated fatty acid present
      in oils derived from plants of the Boraginaceae family. In this study, we
      determined the anti-inflammatory effects of SDA isolated from echium oil on
      lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages.
      SDA significantly downregulated the levels of the inducible nitric oxide synthase
      (iNOS) protein, thereby suppressing the production of nitric oxide (NO) in LPS
      stimulated RAW 264.7 cells. In addition, SDA inhibited the nuclear translocation
      and promoter activity of nuclear factor kappaB (NFkappaB) and the phosphorylation
      of mitogen-activated protein kinases (MAPK) such as extracellular signal
      regulated kinase 1/2, c-jun N terminal kinase, and p38 in LPS-stimulated RAW
      264.7 cells. Our results showed that SDA exerted anti-inflammatory effects by
      suppressing iNOS-mediated NO production via inactivation of NFkappaB and MAPK
      signaling pathways.

PMID- 28744772
TI  - Breakthrough Pain Management with Sublingual Fentanyl Tablets in Patients with
      Cancer: Age Subgroup Analysis of a Multicenter Prospective Study.
AB  - INTRODUCTION: Breakthrough pain (BTP) management in patients with cancer is
      challenging, especially in the elderly. However, no studies examining the
      influence of age on BTP medication have been conducted. The aim of this work was
      to investigate the effect of sublingual fentanyl tablets (SFTs) in terms of
      efficacy, safety, and quality of life in two age categories. METHODS: We
      performed age subgroup analyses (<65 and >=65 years) from a recently completed
      study conducted in Spain. Pain intensity (PI), onset of pain relief, frequency
      and duration of BTP episodes, and adverse events (AEs) were assessed at 3, 7, 15,
      and 30 days. Health-status instruments used were the Short Form 12, version 2 (SF
      12v2) questionnaire, and the Hospital Anxiety and Depression Scale (HADS-A and
      HADS-D). RESULTS: Twenty-six patients were aged <65 years and 54 were aged >=65
      years. SF-12v2 scores did not enhance significantly from baseline. HADS scores
      and PI decreased significantly at the end of the study, particularly in younger
      patients (HADS-A: 19.05 vs. 14.41%; HADS-D: 21.35 vs. 18.57%; PI: 67.23 vs.
      56.30%). Onset of analgesia began in 2-5 min in 63.3% of subjects aged <65 years
      and in 36.4% of subjects aged >65 years. Most patients experienced one to five
      daily episodes after 30 days, and <5% needed a treatment change. AEs were less
      frequently reported in older individuals (20.5 vs. 36.4%). CONCLUSION: Age
      subgroup analyses suggest that SFTs are an effective and safe treatment for the
      management of BTP in cancer patients of all ages. SFTs may offer a well-tolerated
      and efficient option to control cancer BTP in the elderly.

PMID- 28744773
TI  - Alveolar soft part sarcoma: the new primary intracranial malignancy : A case
      report and review of the literature.
AB  - The purpose of this paper is to serve as a reference to aid in the management of
      this poorly understood intracranial malignancy. The authors report their
      experience treating the eighth ostensible case of a primary intracranial alveolar
      soft part sarcoma (ASPS). A 21-year-old man presented to hospital after
      collapsing. He gave a 1-year history of headache, a 2-month history of reduced
      visual acuity and on examination had left facial paraesthesia with left-sided
      incoordination. MRI of the brain revealed a large left posterior fossa mass. The
      patient underwent resection of the tumour with good recovery in function.
      Immunohistochemical analysis of the tumour specimen confirmed an ASPS, and
      multimodal imaging in search of an extra-cranial disease primary was negative. A
      review of the literature yielded only seven other cases of primary intracranial
      ASPS. A variety of diagnostic imaging modalities were employed in search of a
      disease primary, as were various combinations of surgical resection, chemotherapy
      and radiotherapy as treatment. Half of the cases documented delayed disease
      recurrence. The authors discuss the following: the unique radiological and
      immunohistological characteristics of this disease including the potential for
      its misdiagnosis; the investigations required to diagnose a primary intracranial
      ASPS; the efficacy of current medical and surgical treatment options and the
      factors that will aid in prognostication. This is the first review of this new
      primary intracranial malignancy. From our analysis, we offer a joint radiological
      and immunohistochemical algorithm for the diagnosis of primary intracranial ASPS
      and specific operative considerations prior to resection.

PMID- 28744774
TI  - Early onset of efficacy in patients with functional and motility-related
      gastrointestinal disorders : A noninterventional study with Iberogast(r).
AB  - STW 5 (Iberogast(r); Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany)
      contains nine plant extracts and possesses well-documented overall efficacy in
      functional gastrointestinal disorders (FGID). Little is known about the onset of
      symptom relief. Twenty-nine centers in Germany recruited 272 patients with
      established FGID. These patients were treated with STW 5 for approximately 3
      weeks in this noninterventional study. Patients assessed the severity of their
      gastrointestinal complaints before and at defined times after the intake of STW 5
      (10 cm visual analogue scale; VAS). Fifteen minutes after the first dose, the
      severity of gastrointestinal complaints had decreased by 1.4 cm (mean; initial
      mean: 5.2 of 10 cm). After 1 h, more than 90% of the maximum effect of 3.2 cm on
      the 10 cm VAS had been reached. Most patients with symptoms experienced a marked
      improvement within 5, 15 or 30 min of taking STW 5. Absolute improvements were
      larger in patients with more pronounced baseline complaints. Subgroups with upper
      (80% of the study population) and lower FGID (20%) did not present major
      differences. Neither did subgroups by age and duration of complaints. Treatment
      with STW 5 resulted in rapid improvement of symptoms.

PMID- 28744775
TI  - [Bio-psycho-socio or psychotherapeutic medicine - actual development of
      psychosomatics in clinical practice].
AB  - In Germany a model of Psychosomatic Medicine has developed, which integrated
      several psychotherapeutic methods in clinical practice. The concept, which
      focused on disease mechanisms in the human body and the interaction between
      diseased individuals and their environment became a basic psychosomatic research
      strategy and was imlemented in medical care. In this paper the result of a
      psychosomatic development in clinical health care and research and possible
      deficiences are described. Perspectives of development and future tasks of
      Psychosomatic Medicine will be reviewed.

PMID- 28744776
TI  - Between history, art and medicine: the Dresden-Friedrichstadt hospital, its
      Neptune fountain and connections to Vienna.
AB  - The Dresden-Friedrichstadt hospital originated from Marcolini's summer palace. It
      was founded in 1845 and opened in 1849. It is a place where history and art of
      European importance mixes with technical and medical innovations. We reflect on
      the meetings of Napoleon Bonaparte and Metternich in 1812, the creation of the
      famous Neptune fountain by Longuelune and Matielli and two outstanding physicians
      of the 19th century, the surgeon Eduard Zeis, who coined the medical term
      "plastic surgery", and Maximilian Nitze, inventor of the first "modern"
      cystoscope and the father of urology.

PMID- 28744778
TI  - Acute osteomyelitis and septic arthritis in children : A referral hospital-based
      study in Iran.
AB  - Information concerning the epidemiology of acute osteomyelitis (OM), septic
      arthritis (SA) and concurrent OM and SA in children is limited. The aim of this
      study was to describe the epidemiology of OM, SA and concurrent OM and SA in
      children. During the 4 years of the study, 63,999 patients were admitted to the
      Children's Hospital, Tehran, Iran. We identified 111 patients with OM and/or SA
      during the 4-year period. There were 72 cases of OM (11 cases per 10,000
      children) and 90 cases of SA (11 cases per 10,000 children). Concurrent OM and SA
      accounted for 0.17% of all cases (n = 51). The erythrocyte sedimentation rate and
      C-reactive protein were elevated in the majority of both infections.
      Staphylococcus aureus was the most frequent pathogen responsible for both OM and
      SA in any age group. The lower limb was the most frequently affected (femur:
      33/72, 46%; tibia or fibula: 22/72, 31%; foot: 5/72, 7%). The most frequent
      involved joints were hips (n = 31, 34%) and knees (n = 31, 34%). The present
      study showed high frequency of patients with concurrent SA and OM. Therefore,
      prompt recognition and proper diagnosis of pediatric OM and SA is highly
      recommended.

PMID- 28744777
TI  - [Recent standards in management of obstetric anesthesia].
AB  - The following article contains information not only for the clinical working
      anaesthesiologist, but also for other specialists involved in obstetric affairs.
      Besides a synopsis of a German translation of the current "Practice Guidelines
      for Obstetric Anaesthesia 2016" [1], written by the American Society of
      Anesthesiologists, the authors provide personal information regarding major
      topics of obstetric anaesthesia including pre-anaesthesia patient evaluation,
      equipment and staff at the delivery room, use of general anaesthesia, peridural
      analgesia, spinal anaesthesia, combined spinal-epidural anaesthesia, single shot
      spinal anaesthesia, and programmed intermittent epidural bolus.

PMID- 28744779
TI  - Congenital fiber-type disproportion in an ambulatory rehabilitation setting : A
      case report.
AB  - Congenital fiber-type disproportion is a rare condition, histologically
      characterized by a relative type 1 fiber hypotrophy. The main clinical feature is
      mild-to-severe muscle weakness. In this report, we present the case of a 21-year
      old patient with congenital fiber-type disproportion in an outpatient
      rehabilitative setting to evaluate the feasibility and results of an assessment
      battery, including bioimpedance analysis (BIA), dynamometry, 3D gait analysis, 6
      min walk test (6MWT), and the timed up and go test (TUG). The patient had a
      notable decrease in all functional scores. BIA: lean body mass, 38.4 kg (50.2 +/-
      5.3), body fat, 1.6% (12.4 +/- 4.4); hand dynamometry: 18.5 kg left/20.0 kg right
      (44.8 +/- 6.6); walking speed, 58 cm/s (122.7 +/- 11.1), step length, 43.0 cm
      (61.6 +/- 3.5); 6MWT: 478.5 m (638 +/- 44); TUG: 9.4 s (8.1 +/- 1.0). No adverse
      events were reported. The tests used were easily applicable in clinical routine
      and well tolerated by our patient.

PMID- 28744780
TI  - Cloning, overexpression, and characterization of a thermostable nitrilase from an
      Antarctic Pyrococcus sp.
AB  - Nitriles are important chemical building blocks for the synthesis of
      intermediates in fine chemical and pharmaceutical industries. Here, we report a
      new highly thermostable nitrilase from an Antarctic Pyrococcus sp. MC-FB, a
      hyperthermophilic archaeon. A gene that encoded a nitrilase was identified and
      subsequently cloned and overexpressed in Escherichia coli. The recombinant
      nitrilase, named NitMC-FB, is active as a homodimer (60 kDa) with an optimal
      temperature and pH of 90  degrees C and 7.0, respectively. NitMC-FB hydrolyzes
      preferentially aromatic nitriles, being the first aromatic nitrilase from an
      archaeon described so far. The K M and V max parameters were determined to be
      13.9 mM and 3.7 MUmol/min*mg, respectively, with 2-cyanopyridine as the
      substrate. Additionally, the recombinant nitrilase is highly thermostable with a
      half-life of 8 h at 90  degrees C.

PMID- 28744781
TI  - Lung Function in Pregnancy in Langerhans Cell Histiocytosis.
AB  - Pulmonary Langerhans cell histiocytosis (LCH) is a rare disease, affecting
      usually young people. The course of the disease is variable. In some pulmonary
      LCH patients a severe lung destruction and progression in spite of chemotherapy
      is observed, but in others just a cessation of smoking induces a regression of
      the disease. In the present study we seek to determine the influence of pregnancy
      on pulmonary function in LCH patients, an unchartered area of research. We
      addressed the issue by investigating eight pregnant women out of the 45 women
      hospitalized with the diagnosis of pulmonary LCH in the period from 2000 to 2015.
      For five of the eight pregnant women it was the second gestation. The median
      follow-up period was 120 months (range 72-175 months). Ten healthy children were
      born by a C-section. Two spontaneous miscarriages in the seventh week of
      gestation, and one tubal ectopic pregnancy were recorded. We found that pregnancy
      did not significantly influence pulmonary function assessed by the following
      indices: forced expiratory volume in 1 s (FEV1), lung vital capacity (VC), total
      lung capacity (TLC), residual volume (RV), diffusing capacity of the lungs for
      carbon monoxide (DLCO), and the distance and arterial oxygen saturation in 6-min
      walk test. Only one patient in the third trimester of pregnancy experienced
      bilateral pneumothorax, with persistent air leak. In all patients, delivery and
      postpartum period were uneventful. We conclude that pregnancy in pulmonary LCH
      patients is safe and not associated with deterioration of pulmonary function or
      blood oxygenation.

PMID- 28744782
TI  - Storage of nitroglycerin (NTG) admixed with HBOC-201 for 30 days in polyolefin
      plastic bags: a pilot study.
AB  - Hemorrhaged animals have benefited from resuscitation with the hemoglobin-based
      oxygen carrier (HBOC-201). Co-infusion of nitric oxide (NO) via separate
      intravascular lines is effective in attenuating HBOC-induced elevation of blood
      pressure. We tested whether nitroglycerin (NTG) and HBOC-201 can be packaged
      together as a single drug for resuscitation. Since NTG binds easily to plastics
      such as polyvinylchloride, we assessed the stability of this combination in
      oxygen barrier double-layer ethylene-vinyl alcohol/polyolefin bags over a 30-day
      period. Outcome measures indicative of the stability of HBOC/NTG were reported as
      changes in levels of hemoglobin (Hb), methemoglobin (MetHb), NTG, and nitrite
      over time. Individual tightly sealed small aliquots of HBOC/NTG were prepared
      under nitrogen and analyzed in a timely fashion from 0 to 30 days using
      hematology instruments, HPLC, FPLC, and chemiluminescence. The level of NTG in
      the HBOC/NTG mixture was reduced significantly over time whereas it was stable in
      control mixtures of NTG/saline. The level of total Hb in the HBOC/NTG and
      HBOC/saline mixtures remained stable over time. MetHb formed and increased to 6%
      up to day 1 and then slowly decreased in the HBOC/NTG mixture whereas it remained
      unchanged in the HBOC/saline mixture. Nitrite was produced in the HBOC/NTG group
      upon mixing, was increased at day 1, and then became undetectable. The reaction
      between HBOC-201 and NTG occurring upon mixing and developing over time in
      polyolefin bags makes the long-term storage of this mixed combination
      inappropriate.

PMID- 28744783
TI  - Towards the Identification of Hemodynamic Parameters Involved in Arteriovenous
      Fistula Maturation and Failure: A Review.
AB  - Native arteriovenous fistulas have a high failure rate mainly due to the lack of
      maturation and uncontrolled neo-intimal hyperplasia development. Newly
      established hemodynamics is thought to be central in driving the fistula fate,
      after surgical creation. To investigate the effects of realistic wall shear
      stress stimuli on endothelial cells, an in vitro approach is necessary in order
      to reduce the complexity of the in vivo environment. After a systematic review,
      realistic WSS waveforms were selected and analysed in terms of magnitude,
      temporal gradient, presence of reversing phases (oscillatory shear index, OSI)
      and frequency content (hemodynamics index, HI). The effects induced by these
      waveforms in cellular cultures were also considered, together with the materials
      and methods used to cultivate and expose cells to WSS stimuli. The results show a
      wide heterogeneity of experimental approaches and WSS waveform features that
      prevent a complete understanding of the mechanisms that regulate
      mechanotransduction. Furthermore, the hemodynamics derived from the carotid
      bifurcation is the most investigated (in vitro), while the AVF scenario remains
      poorly addressed. In conclusion, standardisation of the materials and methods
      employed, as well as the decomposition of realistic WSS profiles, are required
      for a better understanding of the hemodynamic effects on AVF outcomes. This
      standardisation may also lead to a new classification of WSS features according
      to the risk associated with vascular dysfunction.

PMID- 28744784
TI  - Modeling Left Ventricular Blood Flow Using Smoothed Particle Hydrodynamics.
AB  - This study aims to investigate the capability of smoothed particle hydrodynamics
      (SPH), a fully Lagrangian mesh-free method, to simulate the bulk blood flow
      dynamics in two realistic left ventricular (LV) models. Three dimensional
      geometries and motion of the LV, proximal left atrium and aortic root are
      extracted from cardiac magnetic resonance imaging and multi-slice computed
      tomography imaging data. SPH simulation results are analyzed and compared with
      those obtained using a traditional finite volume-based numerical method, and to
      in vivo phase contrast magnetic resonance imaging and echocardiography data, in
      terms of the large-scale blood flow phenomena usually clinically measured. A
      quantitative comparison of the velocity fields and global flow parameters between
      the in silico models and the in vivo data shows a reasonable agreement, given the
      inherent uncertainties and limitations in the modeling and imaging techniques.
      The results indicate the capability of SPH as a promising tool for predicting
      clinically relevant large-scale LV flow information.

PMID- 28744785
TI  - The Distribution of Miniature Impala Elements and SIX Genes in the Fusarium Genus
      is Suggestive of Horizontal Gene Transfer.
AB  - The mimp family of miniature inverted-repeat transposable elements was previously
      found only in genomes of Fusarium oxysporum and is contextually associated with
      virulence genes in this species. Through extensive comparative analysis of 83 F.
      oxysporum and 52 other Fusarium genomes, we uncovered the distribution of
      different mimp families throughout the genus. We show that (i) mimps are not
      exclusive to F. oxysporum; (ii) pathogenic isolates generally possess more mimps
      than non-pathogenic strains and (iii) two isolates of F. hostae and one F.
      proliferatum isolate display evidence for horizontal transfer of genetic material
      to or from F. oxysporum. Multiple instances of mimp elements identical to F.
      oxysporum mimps were encountered in the genomes of these isolates. Moreover,
      homologs of effector genes (SIX1, 2, 6, 7, 11 and FomAVR2) were discovered here,
      several with very high (97-100%) pairwise nucleotide sequence identity scores.
      These three strains were isolated from infected flower bulbs (Hyacinthus and
      Lilium spp.). Their ancestors may thus have lived in close proximity to
      pathogenic strains of F. oxysporum f. sp. hyacinthi and f. sp. lilii. The Fo f.
      sp. lycopersici SIX2 effector gene was found to be widely distributed (15/18
      isolates) throughout the F. fujikuroi species complex, exhibiting a predominantly
      vertical inheritance pattern. These findings shed light on the potential
      evolutionary mechanism underlying plant-pathogenicity in Fusarium and show that
      interspecies horizontal gene transfer may have occurred.

PMID- 28744786
TI  - Genetic Basis of Exploiting Ecological Opportunity During the Long-Term
      Diversification of a Bacterial Population.
AB  - Adaptive diversification is an essential evolutionary process, one that produces
      phenotypic innovations including the colonization of available ecological niches.
      Bacteria can diverge in sympatry when ecological opportunities allow, but the
      underlying genetic mechanisms are often unknown. Perhaps, the longest-lasting
      adaptive diversification seen in the laboratory occurred during the long-term
      evolution experiment, in which 12 populations of Escherichia coli have been
      evolving independently for more than 65,000 generations from a common ancestor.
      In one population, two lineages, S and L, emerged at ~6500 generations and have
      dynamically coexisted ever since by negative frequency-dependent interactions
      mediated, in part, by acetate secretion by L. Mutations in spoT, arcA, and gntR
      promoted the emergence of the S lineage, although they reproduced only partially
      its phenotypic traits. Here, we characterize the evolved mechanism of acetate
      consumption by the S lineage that enabled invasion and coexistence with the L
      lineage. We identified an additional mutation in acs that, together with the arcA
      mutation, drove an early restructuring of the transcriptional control of central
      metabolism in S, leading to improved acetate consumption. Pervasive epistatic
      interactions within the S genome contributed to the exploitation of this new
      ecological opportunity. The emergence and maintenance of this long-term
      polymorphism is a complex multi-step process.

PMID- 28744787
TI  - On the Possibility of an Early Evolutionary Origin for the Spliced Leader Trans
      Splicing.
AB  - Trans-splicing is a process by which 5'- and 3'-ends of two pre-RNA molecules
      transcribed from different sites of the genome can be joined together to form a
      single RNA molecule. The spliced leader (SL) trans-splicing is mediated by the
      spliceosome and it allows the replacement of 5'-end of pre-mRNA by 5'(SL)-end of
      SL-RNA. This form of splicing has been observed in many phylogenetically
      unrelated eukaryotes. Either the SL trans-splicing (SLTS) originated in the last
      eukaryotic common ancestor (LECA) (or even earlier) and it was lost in most
      eukaryotic lineages, or this mechanism of RNA processing evolved several times
      independently in various unrelated eukaryotic taxa. The bioinformatic comparisons
      of SL-RNAs from various eukaryotic taxonomic groups have revealed the
      similarities of secondary structures of most SL-RNAs and a relative conservation
      of their splice sites (SSs) and Sm-binding sites (SmBSs). We propose that such
      structural and functional similarities of SL-RNAs are unlikely to have evolved
      repeatedly many times. Hence, we favor the scenario of an early evolutionary
      origin for the SLTS and multiple losses of SL-RNAs in various eukaryotic
      lineages.

PMID- 28744788
TI  - Extended high-frequency audiometry as early detection of hearing loss in primary
      Sjogren syndrome.
AB  - The aim of the study is to evaluate hearing function by extended high-frequency
      audiometry in primary Sjogren Syndrome (pSS) and to correlate it with disease
      activity. All patients diagnosed with pSS were recruited within 1 year. Patients
      underwent otologic evaluation, extended high-frequency audiometry, tympanogram,
      and the ESSPRI scale evaluation. A total of 63 (60 female and 3 male) patients
      with mean age 49.5 +/- 9.9 years with pSS were included. We detected a hearing
      loss prevalence of 95.2% (60 patients) in both ears in very high frequencies
      (10000-16,000 Hz). The hearing loss of all patients was sensorineural. There was
      no significant difference between the degree of disease activity and the hearing
      thresholds. We enrolled 188 subjects with a mean age of 47.20 +/- 9.7 years as a
      healthy control group. We compared the hearing thresholds of both ears of
      patients with pSS versus the healthy control group and observed a significant
      difference in frequencies above 500 Hz. Sensorineural hearing loss was found in
      pSS patients in frequencies above 4000 Hz. Sensorineural hearing loss was highly
      prevalent in pSS patients, predominantly in very high frequencies. We claim that
      sensorineural hearing loss could be an associated symptom of primary Sjogren
      syndrome and suggest further research to support this conclusion.

PMID- 28744789
TI  - Decreased olfactory bulb volumes in patients with fibromyalgia syndrome.
AB  - Among the other symptoms, impaired olfactory function such as odor
      identification, threshold, and discrimination have been reported in patients with
      fibromyalgia syndrome (FMS). To investigate olfactory bulb (OB) volumes in FMS,
      by using magnetic resonance imaging (MRI), and to make reasonable suggestions are
      the goals of the present study. The study included 62 individuals as the FMS
      group (n = 30) and the control group (n = 32). MRI examinations were performed by
      a 1.5-T scanner and a standard head coil was used for the images. The coronal T2
      weighted images were used for to measure OB volumes. Right, left, and total OB
      volumes were calculated with the aid of these images. The mean age of the FMS
      group was 44.2 +/- 8.3 years and the control group was 41.7 +/- 3.53 years. The
      mean volume of the right OB was 74.9 +/- 12.4 mm3 in the FMS group and was 92.6
      +/- 12.9 mm3 in the control group. The mean value of the left OB volume was 74.3
      +/- 10.8 mm3 in the FMS group and 92.8 +/- 12.6 mm3 in the control group. The
      mean of the total OB volume was 146.6 +/- 20.81 mm3 in the FMS group and 186.5 +/
      23.5 mm3 in the control group. Left, right, and total OB volumes were
      significantly lower in the FMS group than in the control group (all p < 0.05).
      Female patients with FMS are under the risk of the decreased olfactory bulb
      volumes. This situation should be kept in mind for proper and reasonable
      management of this tough syndrome.

PMID- 28744790
TI  - Cognitive evaluation of patients with glaucoma and its comparison with
      individuals with Alzheimer's disease.
AB  - PURPOSE: To evaluate the cognitive performance of patients with glaucoma and
      compare it to individuals with Alzheimer's disease (AD). METHODS: This is a
      prospective, cross-sectional and case-control study. All subjects were assessed
      using the Mini-Mental State Examination (MMSE) and its subtests verbal fluency,
      word list memory, delayed recall of the word list, word list recognition test,
      Boston naming and constructive praxis from Consortium to Establish a Registry for
      Alzheimer's Disease (CERAD). The results were compared among the groups. RESULTS:
      A total of 50 healthy elderly with a mean age of 71.2 +/- 5.2 years; 41 patients
      with glaucoma (72.2 +/- 4.4 years); and 21 patients with AD (79.0 +/- 7.6 years)
      were included. There was a reduction in all cognitive assessment tests evaluated,
      both for patients with glaucoma, and for those with AD compared with controls (p
      < 0.001 for all). Comparing the patients with glaucoma and AD, it was noted that
      the last had lower cognitive function (p < 0.001), except for the CERAD tests
      Boston (p = 0.1) and praxis (p = 0.6). Glaucoma patients, however, presented
      results of cognitive tests similar to those described for patients with mild AD,
      including lower values for MMSE (21.9 +/- 3.7), Boston (10.6 +/- 2.6) and praxis
      (5.9 +/- 2.3). CONCLUSION: Glaucoma patients had reduction in cognition when
      compared to normal individuals. They were similar to the values reported in the
      literature for patients with mild AD, mostly, and also in some subjects with the
      presence of advanced AD.

PMID- 28744791
TI  - Automatic allograft bone selection through band registration and its application
      to distal femur.
AB  - Clinical reports suggest that large bone defects could be effectively restored by
      allograft bone transplantation, where allograft bone selection acts an important
      role. Besides, there is a huge demand for developing the automatic allograft bone
      selection methods, as the automatic methods could greatly improve the management
      efficiency of the large bone banks. Although several automatic methods have been
      presented to select the most suitable allograft bone from the massive allograft
      bone bank, these methods still suffer from inaccuracy. In this paper, we propose
      an effective allograft bone selection method without using the contralateral
      bones. Firstly, the allograft bone is globally aligned to the recipient bone by
      surface registration. Then, the global alignment is further refined through band
      registration. The band, defined as the recipient points within the lifted and
      lowered cutting planes, could involve more local structure of the defected
      segment. Therefore, our method could achieve robust alignment and high
      registration accuracy of the allograft and recipient. Moreover, the existing
      contour method and surface method could be unified into one framework under our
      method by adjusting the lift and lower distances of the cutting planes. Finally,
      our method has been validated on the database of distal femurs. The experimental
      results indicate that our method outperforms the surface method and contour
      method.

PMID- 28744792
TI  - Expression of 3beta-Hydroxysteroid Dehydrogenase Type 1 in Breast Cancer is
      Associated with Poor Prognosis Independent of Estrogen Receptor Status.
AB  - BACKGROUND: Human 3beta-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a
      vital role in steroidogenesis in breast tumors and may therefore be a suitable
      target for treatment of breast cancer. This study investigated the role of HSD3B1
      in the pathogenesis of breast cancer in clinical and experimental settings.
      METHODS: Expression of HSD3B1 in primary tumors of 258 breast cancer patients was
      evaluated by immunohistochemistry. Screening of breast cancer cell lines
      indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects
      from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in
      vivo. RESULTS: The findings showed that 44% of the 258 breast cancers were HSD3B1
      positive. The HSD3B1-positivity was associated with advanced-stage disease (p =
      0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor
      subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an
      HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells.
      Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a
      murine xenograft tumor model indicated that trilostane significantly slowed tumor
      growth. CONCLUSIONS: Expression of HSD3B1 in breast cancer is negatively
      associated with prognosis. The study found HSD3B1 to be a potential therapeutic
      target for breast cancer independent of estrogen receptor status.

PMID- 28744793
TI  - Application of liquid biopsy in precision medicine: opportunities and challenges.
AB  - Precision medicine for cancer patients aims to adopt the most suitable treatment
      options during diagnosis and treatment of individuals. Detecting circulating
      tumor cell (CTC) or circulating tumor DNA (ctDNA) in plasma or serum could serve
      as liquid biopsy, which would be useful for numerous diagnostic applications.
      Liquid biopsies can help clinicians screen and detect cancer early, stratify
      patients to the most suitable treatment and real-time monitoring of treatment
      response and resistance mechanisms in the tumor, evaluate the risk for metastatic
      relapse, and estimate prognosis.We summarized the advantages and disadvantages of
      tissue and liquid biopsies.We also further compared and analyzed the advantages
      and limitations of detecting CTCs, ctDNAs, and exosomes. Furthermore, we reviewed
      the literature related with the application of serum or plasma CTCs, ctDNAs, and
      exosomes for diagnosis and prognosis of cancer.We also analyzed their
      opportunities and challenges as future biomarkers. In the future, liquid biopsies
      could be used to guide cancer treatment. They could also provide the ideal scheme
      to personalize treatment in precision medicine.

PMID- 28744794
TI  - Propensity score-matched study and meta-analysis of cumulative outcomes of day
      2/3 versus day 5/6 embryo transfers.
AB  - The superiority of the cumulative outcomes of day 5/6 embryo transfer to those of
      day 2/3 embryo transfer in infertile couples has been debated. This retrospective
      study included data collected from 1051 patients from July 2011 to June 2014.
      Multiple maternal baseline covariates were subjected to propensity score matching
      analysis, and each day 5/6 group woman was matched to one day 2/3 group woman. A
      systematic meta-analysis was conducted to validate the results. After matching
      was completed, 217 patients on the day 2/3 group were matched with those on the
      day 5/6 group, and no significant differences in the baseline characteristics
      were observed between the two groups. The cumulative pregnancy rate (57.14% vs.
      53.46%, OR 1.16, 95% CI 0.79-1.70) and cumulative live birth rate (53.00% vs.
      49.77%, OR 1.14, 95% CI 0.78-1.66) of day 5/6 embryo transfers were higher than
      those of day 2/3 embryo transfers, but this difference was not significant. The
      mean cycles per live birth and mean days per live birth in the day 5/6 group were
      significantly lower than those in the day 2/3 group. This study demonstrated that
      day 5/6 embryo transfer is a more cost-effective and time-efficient policy than
      day 2/3 embryo transfer to produce a live baby.

PMID- 28744795
TI  - Prediction of Fetal Darunavir Exposure by Integrating Human Ex-Vivo Placental
      Transfer and Physiologically Based Pharmacokinetic Modeling.
AB  - BACKGROUND: Fetal antiretroviral exposure is usually derived from the cord-to
      maternal concentration ratio. This static parameter does not provide information
      on the pharmacokinetics in utero, limiting the assessment of a fetal exposure
      effect relationship. OBJECTIVE: The aim of this study was to incorporate
      placental transfer into a pregnancy physiologically based pharmacokinetic model
      to simulate and evaluate fetal darunavir exposure at term. METHODS: An existing
      and validated pregnancy physiologically based pharmacokinetic model of maternal
      darunavir/ritonavir exposure was extended with a feto-placental unit. To
      parameterize the model, we determined maternal-to-fetal and fetal-to-maternal
      darunavir/ritonavir placental clearance with an ex-vivo human cotyledon perfusion
      model. Simulated maternal and fetal pharmacokinetic profiles were compared with
      observed clinical data to qualify the model for simulation. Next, population
      fetal pharmacokinetic profiles were simulated for different maternal
      darunavir/ritonavir dosing regimens. RESULTS: An average (+/-standard deviation)
      maternal-to-fetal cotyledon clearance of 0.91 +/- 0.11 mL/min and fetal-to
      maternal clearance of 1.6 +/- 0.3 mL/min was determined (n = 6 perfusions).
      Scaled placental transfer was integrated into the pregnancy physiologically based
      pharmacokinetic model. For darunavir 600/100 mg twice a day, the predicted fetal
      maximum plasma concentration, trough concentration, time to maximum plasma
      concentration, and half-life were 1.1, 0.57 mg/L, 3, and 21 h, respectively. This
      indicates that the fetal population trough concentration is higher or around the
      half-maximal effective darunavir concentration for a resistant virus (0.55 mg/L).
      CONCLUSIONS: The results indicate that the population fetal exposure after oral
      maternal darunavir dosing is therapeutic and this may provide benefits to the
      prevention of mother-to-child transmission of human immunodeficiency virus.
      Moreover, this integrated approach provides a tool to prevent fetal toxicity or
      enhance the development of more selectively targeted fetal drug treatments.

PMID- 28744796
TI  - Pharmacokinetics of ABT-122, a TNF-alpha- and IL-17A-Targeted Dual-Variable
      Domain Immunoglobulin, in Healthy Subjects and Patients with Rheumatoid
      Arthritis: Results from Three Phase I Trials.
AB  - BACKGROUND AND OBJECTIVE: ABT-122 is a dual-variable domain immunoglobulin that
      neutralizes both tumor necrosis factor-alpha and interleukin-17A, with the goal
      of achieving greater clinical efficacy than can be achieved by blocking either
      cytokine alone. This work characterized the pharmacokinetics of ABT-122 in
      healthy subjects and in patients with rheumatoid arthritis. METHODS: ABT-122
      pharmacokinetics was evaluated in three phase I studies. In Study 1, single
      intravenous (0.1, 0.3, 1, 3, and 10 mg/kg) and subcutaneous (0.3, 1, and 3 mg/kg)
      doses were evaluated in healthy subjects. In Studies 2 and 3, multiple
      subcutaneous doses (1 mg/kg every other week or 0.5-3 mg/kg every week) were
      evaluated for 8 weeks in patients with rheumatoid arthritis on stable
      methotrexate therapy. Pharmacokinetic data were available from 48 healthy
      subjects and 31 patients with rheumatoid arthritis. RESULTS: ABT-122 showed multi
      exponential disposition with more than dose-proportional exposures at the 0.1-1
      mg/kg doses and approximately dose-proportional exposures at doses >=1 mg/kg. ABT
      122 absolute subcutaneous bioavailability was approximately 50% with maximum
      serum concentrations observed 3-4 days after dosing. Steady state was achieved by
      week 6 of subcutaneous dosing. ABT-122 maximum serum concentration-to-trough
      concentration ratio was 2.6 for every other week dosing and 1.3 for every week
      dosing, corresponding to an effective half-life of 10-18 days. ABT-122 median
      area under the serum concentration-time curve accumulation ratio was 3.8-4.8 with
      every week dosing. Measureable antidrug antibodies were observed in all 48
      subjects in Study 1 by day 15 post-dose and 19 of 31 ABT-122-treated patients in
      Studies 2 and 3 [median time to appearance of antidrug antibodies of 64 days
      (range 15-92 days)]. No dose-limiting toxicities were observed in these studies
      and the maximum tolerated dose was not identified. CONCLUSIONS: Results from
      these three phase I studies supported testing ABT-122 every week and every other
      week regimens in phase II trials in subjects with rheumatoid and psoriatic
      arthritis. Study 2 (EudraCT: 2012-003448-54); Study 3 (NCT01853033).

PMID- 28744797
TI  - Reconstructing the immune system with lentiviral vectors.
AB  - Lentiviral vectors (LVs) developed in the past two decades for research and pre
      clinical purposes have entered clinical trials with remarkable safety and
      efficacy performances. Development and clinical testing of LVs for improvement of
      human immunity showed major advantages in comparison to other viral vector
      systems. Robust and persisted transduction efficiency of blood cells with LVs,
      resulted into a broad range of target cells for immune therapeutic approaches:
      from hematopoietic stem cells and precursor cells for correction of immune
      deficiencies, up to effector lymphoid and myeloid cells. T cells engineered for
      expression of chimeric antigen receptors (CARs) or epitope-specific transgenic T
      cell receptors (TCRs) are in several cancer immune therapy clinical trials
      worldwide. Development of engineered dendritic cells is primed for clinical
      trials for cancer and chronic infections. Technological adaptations for ex vivo
      cell manipulations are here discussed and presented based on properties and uses
      of the target cell. For future development of off-shelf immune therapies, direct
      in vivo administration of lentiviral vectors is warranted and intended.
      Approaches for lentiviral in vivo targeting to maximize immune therapeutic
      success are discussed.

PMID- 28744798
TI  - Ultrasound-guided hydrostatic enema for meconium obstruction in extremely low
      birth weight infants: a preliminary report.
AB  - Meconium obstruction (MO) in extremely low birth weight (ELBW) infants is a
      challenging disease to treat. We performed ultrasound-guided hydrostatic enema on
      six ELBW infants diagnosed with MO. We consider this procedure to be safe and
      effective, and recommend it as a treatment for MO in ELBW infants.

PMID- 28744799
TI  - Changes in the brain antioxidant profile after chronic vanadium administration in
      mice.
AB  - Vanadium is known to induce reactive oxygen species (ROS) in biological systems.
      Exposure to vanadium has been linked to neurological defects affecting the
      central nervous system (CNS) early in life and culminates later to
      neurodegeneration. This study was designed to evaluate the effects of chronic
      vanadium exposure on antioxidant profile in mice, and progressive changes after
      withdrawal from treatment. A total of 85 male BALB/c mice (4 weeks old) were used
      for the experiment and were divided into three groups of vanadium exposed (3
      mg/kg i.p at 3-18 months treatment), matched controls, and animals exposed to
      vanadium for three months and thereafter vanadium was withdrawn. Vanadium
      exposure caused significant increases (p<0.05) in levels of malondialdehyde
      (MDA), hydrogen peroxide (H2O2) generation and nitric oxide with a concomitant
      decrease (p<0.05) in the activities of superoxide dismutase (SOD), glutathione
      peroxidase (GPx), glutathione-S-transferase and a decline in the level of reduced
      glutathione (GSH) after 6 months of vanadium exposure in the brain. This trend
      continued in all vanadium-exposed groups (9, 12, 15 and 18 months) relative to
      the matched controls. Withdrawal after 3 months of vanadium exposure
      significantly reversed oxidative stress in intoxicated mice from 9 to 15 months
      after vanadium withdrawal. We have shown that chronic administration of vanadium
      led to oxidative stress in the brain which is reversible only after a long period
      of vanadium withdrawal.

PMID- 28744801
TI  - A retrospective comparison between delayed and early hip fracture surgery in
      patients taking clopidogrel: same total bleeding but different timing of blood
      transfusion.
AB  - PURPOSE: Managing hip fracture surgery in patients taking clopidogrel is
      challenging. The optimal timing for surgery remains unclear. Early surgery in
      such patients potentially increases peri-operative bleeding, whereas delayed
      surgery has been shown to be associated with worse postoperative outcomes. The
      aim of this study was to investigate whether a delay to surgery affects total
      blood loss, bleeding kinetics, blood transfusion requirements, or post-operative
      outcomes. METHODS: A retrospective monocentric study including all hip fracture
      patients treated with clopidogrel between 2011 and 2016 (39 patients) was carried
      out. Patients who underwent delayed surgery after withholding clopidogrel for
      five days or more, from 2011 to 2013, were compared to patients who benefited
      from earlier surgical procedures (within 48 hours of admission) from 2014 to
      2016. RESULTS: Total blood loss, amount of blood transfusion and rate of
      postoperative complications did not differ between the two groups. However, the
      timing of bleeding was significantly different; blood loss occurred during the
      pre-operative phase in the delayed surgery group (p < 0.0001), whereas it
      occurred during the intra-operative phase in the early surgery group (p = 0.005).
      The length of the hospital stay was significantly shorter for the early surgery
      group than for the delayed surgery group: 11 +/- three versus 15 +/- four days (p
      = 0.004). CONCLUSIONS: Early surgical treatment of hip fracture in patients
      receiving clopidogrel does not increase the overall red blood cell loss or the
      transfusion requirement, but may affect the timing of blood transfusion. Hip
      fracture surgery should preferably be performed without delay in patients taking
      clopidogrel.

PMID- 28744800
TI  - Risk factors for infectious complications after open fractures; a systematic
      review and meta-analysis.
AB  - PURPOSE: The purpose of this study was to identify risk factors for the
      development of infection after open fracture fixation. METHODS: A comprehensive
      search in all scientific literature of the last 30 years was performed in order
      to identify patient-, trauma-, diagnosis- and treatment-related risk factors.
      Studies were included when infectious complications were assessed in light of one
      or more risk factors. A meta-analysis was performed. Risk ratios (RR) or risk
      differences (RD) with 95% confidence intervals were calculated. RESULTS: A total
      of 116 manuscripts were included. Male gender (RR 1.42), diabetes mellitus (DM)
      (RR 1.72), smoking (RR1.29), a lower extremity fracture (RR 1.94), Gustilo
      Anderson grade III open fracture (RR 3.01), contaminated fracture (RR 7.85) and
      polytrauma patients (RR 1.49) were identified as statistically significant risk
      factors for the development of infectious complications. Of the treatment-related
      risk factors, only pulsatile lavage was associated with a higher infectious
      complication rate (RR 2.70). CONCLUSION: A number of risk factors for the
      development of infections after open fractures have been identified in the
      available literature. These factors should still be tested for independence in a
      multivariable model. Prospective, observational studies are needed to identify
      and quantify individual risk factors for infection after open fracture fixation.

PMID- 28744802
TI  - Survival of the Scandinavian total ankle replacement (STAR): results of ten to
      nineteen years follow-up.
AB  - PURPOSE: The purpose of this study was to evaluate survival and clinical outcome
      of the Scandinavian total ankle replacement (STAR) prosthesis after a minimum of
      ten years up to a maximum of 19 years. METHODS: Fifty STAR prostheses in 46
      patients with end stage ankle osteoarthritis operated between 1996 and 2006 by
      the same surgeon (MH) were included. Minimal follow-up was ten years (median 14.6
      years, 95% confidence interval [CI] 12.9-16.4). Clinical (Kofoed score) and
      radiological assessments were taken before the operation and at one, ten (+2),
      and 16 (+/-3) years after implantation. The primary endpoint was defined as
      exchange of the whole prosthesis or conversion to arthrodesis (def. 1), exchange
      of at least one metallic component (def. 2), or exchange of any component
      including the inlay (due to breakage or wear) (def. 3). Survival was estimated
      according to Kaplan-Meier. Further reoperations related to STAR were also
      recorded. RESULTS: The ten year survival rate was (def. 1) 94% (CI 82-98%), (def.
      2) 90% (CI, 77-96%), and (def. 3) 78% (CI 64-87%). The 19-year survival rate was
      (def. 1) 91% (CI 78-97%), (def. 2) 75% (CI 53-88%), and (def. 3) 55% (CI 34-71%).
      Considering any re-operations related to STAR, 52% (26/50) of prostheses were
      affected by re-operations. Mean pre-operative Kofoed score was 49, which improved
      to 84 after one year (n = 50), to 90 after ten years (n = 46), and to 89 after 16
      years (n = 28). CONCLUSIONS: The survival rate for def. 1 and 2 was high.
      However, re-operations occurred in 52% of all STAR prosthesis. STUDY DESIGN:
      Retrospective cohort study, evidence Level 4.

PMID- 28744804
TI  - Affective symptoms and determinants of health-related quality of life in Mexican
      people with epilepsy.
AB  - Epilepsy is known to be associated with multiple psychiatric comorbidities, such
      as depression, sleep-disorders, and anxiety. The objective of this study was to
      determine the prevalence and impact of affective symptoms over health-related
      quality of life (QOL) in Mexican people with epilepsy (PWE). We performed a cross
      sectional observational study on 73 consecutive PWE and corresponding age- and
      sex-matched controls. HrQOL was assessed using the QOLIE-10 (QOL in Epilepsy-10)
      instrument. Clinical and demographic characteristics were recorded, and
      instruments evaluating depressive/anxiety symptoms, sleep quality, and insomnia
      were completed. PWE had more depressive/anxiety symptoms when compared with
      controls. QOLIE-10 scores were significantly inversely correlated with poor sleep
      quality, insomnia symptoms, depressive/anxiety symptoms, and number of anti
      epileptic drugs used, but not with seizure type or number of seizures per month.
      A poor QOL was independently associated only with anti-epileptic drug
      polytherapy. PWE are burdened with depressive/anxiety symptoms at alarming rates.
      The presence of depressive symptoms along with sleep disturbances and more
      significantly, anti-epileptic drug polytherapy, appears to negatively impact QOL,
      to a greater degree than short-term seizure control.

PMID- 28744803
TI  - Xanthoceraside modulates neurogenesis to ameliorate cognitive impairment in
      APP/PS1 transgenic mice.
AB  - Neuronal loss is reported to be an important pathological process in Alzheimer's
      disease (AD). Neurogenesis is a process of generation of new neurons to fill the
      neuronal loss. Xanthoceraside has been shown to attenuate the cognitive deficits
      in several AD animal models. However, little is known about the effect of
      xanthoceraside on neurogenesis in APP/PS1 transgenic mice. Thus, in this study,
      we investigated whether xanthoceraside can ameliorate learning and memory
      impairment by promoting NSCs proliferation and neuronal differentiation. The
      results suggested that xanthoceraside significantly ameliorated the cognitive
      impairment and induced NSCs proliferation and neuronal differentiation in APP/PS1
      transgenic mice. Meanwhile, in vitro study revealed that xanthoceraside increased
      the size of NSCs and induced NSCs differentiation into neurons compared with
      amyloid beta-peptide (25-35) (Abeta25-35) treatment. Furthermore, we found that
      xanthoceraside significantly increased the expression of Wnt3a and p-GSK3beta,
      decreased the expression of p-beta-catenin, and induced nuclear translocation of
      beta-catenin in APP/PS1 transgenic mice. Furthermore, in vitro study found that
      the effect of xanthoceraside on inducing NSCs proliferation and neuronal
      differentiation were inhibited by Wnt pathway inhibitor Dickkopf-1 (Dkk-1). Our
      data demonstrated that xanthoceraside may promote the proliferation and
      differentiation of NSCs into neurons by up-regulating the Wnt/beta-catenin
      pathway to fill the neuronal loss, thereby improving learning and memory
      impairment in APP/PS1 transgenic mice.

PMID- 28744805
TI  - Combination mode of physiological signals for diagnosis of OSAS using portable
      monitor.
AB  - PURPOSE: Portable respiratory monitor (PRM) has been proposed for pre-diagnosis
      of obstructive sleep apnea syndrome (OSAS). However, discrepant physiological
      signal combinations were rarely studied for diagnostic assessment of OSAS. This
      study was designed to evaluate combination modes of key physiological signals
      collected by portable sensor modules for OSAS screening in comparison with
      polysomnography (PSG). METHODS: People with suspected OSAS were submitted to PRM
      at a sleep laboratory monitoring concurrently with PSG. The diagnostic accuracy
      was assessed by sensitivity, specificity, Pearson correlation coefficients, kappa
      statistic, and Bland-Altman plot. Four combination modes of PRM, including mode 1
      with single nasal airflow, mode 2 with airflow plus body activity, mode 3 with
      airflow plus SpO2, tri-combination mode 4 with airflow plus SpO2 plus activity
      were studied. RESULTS: Thirty-five subjects (69% men, mean age +/- SD, 49 +/- 12
      years) with averaged apnea-hypopnea index (AHI) of 36 +/- 29 events/h were
      tested. Excluding incomplete recordings, 33 valid samples were analyzed. All PRM
      modes demonstrated good concordances with PSG in diagnostic outcomes. Tri
      combination mode had optimum with sensitivity of 96.5%, specificity of 100%, +LR
      of 4, -LR of 0.03, and kappa coefficient of 0.85 for screening OSAS holding AHI
      >=5. Its Bland-Altman plots also showed the smallest dispersion. CONCLUSIONS:
      This study used clinical comparison to demonstrate diagnostic accuracy of PRM
      with different physiological signal combination. The combination of respiratory
      airflow, oxygen saturation, and body activity provided sufficiently high accuracy
      for diagnosing OSAS. Single respiratory airflow sensor as the simplest PRM was
      also feasible for pre-screening OSAS.

PMID- 28744806
TI  - Interleukin-10 production and T cell-suppressive capacity in B cell subsets from
      atherosclerotic apoE -/- mice.
AB  - The evidence regarding the role of regulatory B cells (Breg) in atherosclerosis
      are scarce, and there are contradictory data about their atheroprotective
      properties. Due to the demonstrated protective function of Breg in different
      inflammatory diseases mainly through interleukin-10 (IL-10) production, the
      knowledge of their participation in atherosclerosis immunopathology would be very
      valuable. To further study which B cell subsets participate in IL-10 production
      and their regulatory role, splenocytes from apolipoprotein-E-deficient mice were
      evaluated by ex vivo and in vitro cultures. Atherosclerotic mice had increased
      frequency of IL-10+ B cells, which presented high CD1d, CD19, and IgM, but
      variable CD5, CD21, and CD23 expression. IL-10+ B cells were not enriched in B
      cell subsets previously reported as Breg. Increased frequency of IL-10+ B cells
      with transitional 1-like (T1-like) and follicular (FO) and reduced CD5+ and
      marginal zone (MZ) phenotypes were observed ex vivo. Increased frequency of IL
      10+ B cells with T1-like and MZ, and decreased IL-10+ FO and T2 phenotypes were
      also observed in vitro. To determine regulatory capacity of B cells in the
      atherosclerotic model, each subset were co-cultured with CD4+CD25- T cells. CD5+,
      FO, MZ, and T1-like cells from atherosclerotic mice exhibited regulation in an IL
      10-dependent manner. However, only FO cells decreased both frequency of
      interferon gamma (IFN-gamma)+ and tumor necrosis factor alpha (TNF-alpha)+ and
      proliferation of T cells. Finally, splenocytes showed increased frequency of IFN
      gamma+ and TNF-alpha+ cells only when FO-depleted B cells were evaluated. These
      results suggest that mainly FO B cells can modulate in some level the
      inflammatory responses observed in atherosclerosis.

PMID- 28744807
TI  - The effectiveness of low-dose and high-dose tranexamic acid in posterior lumbar
      interbody fusion: a double-blinded, placebo-controlled randomized study.
AB  - PURPOSE: Tranexamic acid is a proven drug used for reduction of intraoperative
      blood loss in spinal surgery. However, optimal dosing considering risk/benefits
      is not well established owing to the heterogeneity in patient selection and
      surgical procedures of previous studies. This study aimed to evaluate the
      effectiveness and safety of various tranexamic acid regimens in reducing
      perioperative blood loss in single-level posterior lumbar interbody fusion
      (PLIF). METHODS: Patients were randomly grouped into three different
      interventions: low-dose tranexamic acid (LD), high-dose tranexamic acid (HD), and
      placebo-controlled (PC) groups. The HD and LD groups received 10 and 5 mg/kg of
      bolus loading dose and 2 and 1 mg/kg of continuous infusion until 5 h after
      surgery, respectively. Data on patient demographics and preoperative and 24-h
      postoperative laboratory values were collected. Outcome parameters include
      intraoperative blood loss, 24-h postoperative blood loss, and blood loss during
      removal of the last drain. RESULTS: Seventy-two patients (mean age 63.3 +/- 7.6
      years) showed similar baseline characteristics. Intraoperatively, blood loss was
      reduced by the administration of tranexamic acid (P = 0.04), contributed
      predominantly by a difference between the LD and HD groups (123 mL; P < 0.01).
      The 24-h postoperative blood loss was reduced (P < 0.01), contributed
      predominantly by a difference between the PC and LD groups (144 mL; P = 0.02).
      During the removal of the last drain, statistical difference was found between
      the PC and HD groups (125 mL; P = 0.00). No complications or side effects from
      tranexamic acid use were noted. CONCLUSION: Tranexamic acid administration for
      single-level PLIF was effective and safe in reducing perioperative blood loss in
      a dose-dependent manner. An HD regimen comprising 10 mg/kg of bolus loading dose
      and 2 mg/kg/h of continuous infusion is recommended. LEVEL OF EVIDENCE: Level 1
      study according to Oxford Centre for Evidence-Based Medicine 2011 Levels of
      Evidence.

PMID- 28744808
TI  - Answer to the Letter to the Editor of A. Piazzolla et al. concerning "Normative
      values for the spine shape parameters using 3D standing analysis from a database
      of 268 asymptomatic Caucasian and Japanese subjects" by J. C. Le Huec et al. Eur
      Spine J (2016) 25:3630-3637.

PMID- 28744809
TI  - Vimentin is a crucial target for anti-metastasis therapy of nasopharyngeal
      carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck cancer, with
      tendency to spread to regional lymph nodes and distant organs at early stage.
      Vimentin, a major cytoskeletal protein constituent of the intermediate filament,
      plays a critical role in the epithelial-mesenchymal transition. Overexpression of
      vimentin is considered to be a critical prerequisite for metastasis in numerous
      human cancers. Therefore, targeting vimentin for cancer therapy has gained a lot
      of interest. In the present study, we detected vimentin expression in NPC tissues
      and found that overexpression of vimentin is associated with poor prognosis of
      NPC patients. Silencing of vimentin in NPC CNE2 cells by RNAi suppresses cells
      migration and invasion in vitro. However, blocking vimentin did not affect cell
      proliferation of CNE2 cells. In addition, the in vivo metastatic potential of
      CNE2 cells transfected with Vimentin shRNA was suppressed in a nude mouse model
      of pulmonary metastasis. Silencing of Vimentin in CNE2 cells leads to a decrease
      of microvessel density and VEGF, CD31, MMP2, and MMP9 expressions in pulmonary
      metastatic tumors. Importantly, we found that it is easier for the tumor cells
      from the high vimentin-expressing pulmonary metastatic tumors to reinvade the
      microvessel and to form stable tumor plaques attached to the endothelial cells,
      which resemble the resource of circulating tumor cells and are very hard to
      eliminate. However, depletion of vimentin inhibits the formation of vascular
      tumor plaques. Our findings suggest that RNAi-based vimentin silencing may be a
      potential and promising anti-metastatic therapeutic strategy for NPC.

PMID- 28744810
TI  - Kruppel-like factor 4 regulates the expression of inducible nitric oxide synthase
      induced by TNF-alpha in human fibroblast-like synoviocyte MH7A cells.
AB  - Kruppel-like factor 4 (KLF4), a zinc finger transcription factor, has been
      implicated in the inflammation mediated by macrophages and endothelial cells by
      regulating the expression of inflammatory mediators. Here, we investigated
      whether KLF4 affects the expression of inducible nitric oxide synthase (iNOS), an
      important inflammatory mediator, in the human RA fibroblast-like synovial cell
      line MH7A. A pcDNA3.1-KLF4 plasmid or short interfering RNA KLF4 was transfected
      into MH7A cells, and the iNOS expression and nitric oxide (NO) production were
      analyzed by quantitative PCR, immunoblotting, and nitrite measurement. The iNOS
      promoter activity was determined by luciferase assay. The results showed
      overexpression of KLF4 increased iNOS expression and NO production in the
      presence or absence of TNF-alpha. Conversely, KLF4 knockdown markedly reduced
      iNOS expression and NO production induced by TNF-alpha. KLF4 activated the
      transcription activity of iNOS promoter in MH7A cells stimulated by TNF-alpha.
      This study indicates that KLF4 is important for regulating the expression of iNOS
      by TNF-alpha in human synoviocytes.

PMID- 28744811
TI  - Evidence of vanillin binding to CAMKIV explains the anti-cancer mechanism in
      human hepatic carcinoma and neuroblastoma cells.
AB  - Human calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of
      Ser/Thr kinase family, and is associated with different types of cancer and
      neurodegenerative diseases. Vanillin is a natural compound, a primary component
      of the extract of the vanilla bean which possesses varieties of pharmacological
      features including anti-oxidant, anti-inflammatory, anti-bacterial and anti
      tumor. Here, we have investigated the binding mechanism and affinity of vanillin
      to the CAMKIV which is being considered as a potential drug target for cancer and
      neurodegenerative diseases. We found that vanillin binds strongly to the active
      site cavity of CAMKIV and stabilized by a large number of non-covalent
      interactions. We explored the utility of vanillin as anti-cancer agent and found
      that it inhibits the proliferation of human hepatocyte carcinoma (HepG2) and
      neuroblastoma (SH-SY5Y) cells in a dose-dependent manner. Furthermore, vanillin
      treatment resulted into the significant reduction in the mitochondrial membrane
      depolarization and ROS production that eventually leads to apoptosis in HepG2 and
      SH-SY5Y cancer cells. These findings may offer a novel therapeutic approach by
      targeting the CAMKIV using natural product and its derivative with a minimal side
      effect.

PMID- 28744812
TI  - In vivo effects of dexamethasone on blood gene expression in ataxia
      telangiectasia.
AB  - Ataxia telangiectasia (AT) is a rare incurable genetic disease caused by
      biallelic mutations in the Ataxia telangiectasia-mutated gene. Intra-erythrocyte
      infusion of dexamethasone improves clinical outcomes in AT patients; however, the
      molecular mechanisms that lead to this improvement remain unknown. Hence, to gain
      a better understanding of these mechanisms, we assessed the effects of
      glucocorticoid administration on gene expression in the blood of AT patients.
      Whole blood was obtained from nine children enrolled in a phase two clinical
      trial, who were being treated with dexamethasone (AT Dexa), from six untreated AT
      patients (AT) and from six healthy volunteers (WT). CodeLink Whole Genome
      Bioarrays were used to assess transcript expression. The reliability of the
      differentially expressed genes (DEGs) was verified by qRT-PCR analysis. The
      enriched Gene Ontology (GO) terms and the pathways of the Kyoto Encyclopedia of
      Genes and Genomes (KEGG) of DEGs obtained by group comparisons were achieved
      using the Database for Annotation, Visualization and Integrated Discovery
      (DAVID). Functional network analyses were computed by Reactome FI. The likely
      involved transcription factors were revealed by iRegulon. Among the identified
      DEGs influenced by the pathology and restored by dexamethasone, we detected 522
      upregulated probes coding for known proteins, while 22 probes were downregulated,
      as they were in healthy subjects. These results provide useful information and
      represent a first step towards gaining a better understanding of the underlying
      mechanisms of the effects of dexamethasone on AT patients.

PMID- 28744813
TI  - Inhibition of protein kinase CK2 sensitizes non-small cell lung cancer cells to
      cisplatin via upregulation of PML.
AB  - Non-small cell lung carcinoma (NSCLC), a malignancy of lungs, is very aggressive
      and usually ends up with a dismal prognosis. Cisplatin (CDDP)-based systemic
      chemotherapy is the main pharmaceutical approach for treating NSCLC, but its
      effect is discounted by some hitherto unknown reasons. Thus, this study is
      dedicated to improving the efficacy of CDDP. Our results show that combining use
      of CDDP with CK2 siRNA or inhibitor is more efficient in suppressing cancer cell
      growth and promoting apoptosis than use of CDDP alone. The underlying mechanism
      is that CDDP has two pathways to go: one is that it directly induces apoptosis
      and the other is that it activates CK2, which suppresses proapoptosis gene
      promyelocytic leukemia (PML). In conclusion, inhibiting CK2 can enhance
      sensitivity of CDDP to NSCLC cancer cells through PML.

PMID- 28744814
TI  - Arg913Gln of SLC12A3 gene promotes development and progression of end-stage renal
      disease in Chinese type 2 diabetes mellitus.
AB  - Whether the Arg913Gln variation (rs11643718, G/A) of SLC12A3 contributes to
      diabetic nephropathy (DN) remains controversial. We undertook a case-control
      study to evaluate the association of the SLC12A3-Arg913Gln variation with the
      risk of end-stage renal disease (ESRD) in Chinese type 2 diabetes mellitus (T2DM)
      patients undergoing hemodialysis, and analyzed the genotype-phenotype
      interaction. Unrelated Chinese T2DM patients (n = 372) with diabetic retinopathy
      were classified into the non-DN (control) group (n = 151; duration of T2DM >15
      years, no signs of renal involvement) and the DN-ESRD group (n = 221; ESRD due to
      T2DM, receiving hemodialysis). Polymerase chain reaction-direct sequencing was
      used to genotype the SLC12A3-Arg913Gln variation for all participants. The
      frequency of the GA+AA genotype in the DN-ESRD group was significantly higher
      than that of the non-DN group (23.1 vs. 9.9%; adjusted OR 2.2 (95% CI 1.3-4.5), P
      = 0.019). In the non-DN group, GA+AA carriers had a significantly higher urinary
      albumin excretion rate (UAER) and diastolic blood pressure compared with GG
      carriers (both P < 0.05). The SLC12A3-Arg913Gln variation may be associated with
      increased blood pressure and UAER and, therefore, could be used to predict the
      development and progression of DN-ESRD in Chinese T2DM patients undergoing
      hemodialysis.

PMID- 28744815
TI  - Mammalian Diaphanous-related formin-1 restricts early phases of influenza
      A/NWS/33 virus (H1N1) infection in LLC-MK2 cells by affecting cytoskeleton
      dynamics.
AB  - Viruses depend on cellular machinery to efficiently replicate. The host
      cytoskeleton is one of the first cellular systems hijacked by viruses in order to
      ensure their intracellular transport and promote the development of infection.
      Our previous results demonstrated that stable microfilaments and microtubules
      interfered with human influenza A/NWS/33 virus (H1N1) infection in semi
      permissive LLC-MK2 cells. Although formins play a key role in cytoskeletal
      remodelling, few studies addressed a possible role of these proteins in
      development of viral infection. Here, we have demonstrated that mammalian
      Diaphanous-related formin-1 (mDia1) is involved in the control of cytoskeleton
      dynamics during human influenza A virus infection. First, by employing
      cytoskeleton-perturbing drugs, we evidenced a cross-talk occurring between
      microtubules and microfilaments that also has implications on the intracellular
      localization of mDia1. In influenza A/NWS/33 virus-infected LLC-MK2 cells, mDia1
      showed a highly dynamic intracellular localization and partially co-localized
      with actin and tubulin. A depletion of mDia1 by RNA-mediated RNA interference was
      found to improve the outcome of influenza A/NWS/33 virus infection and to
      increase the dynamics of microfilament and microtubule networks in LLC-MK2 cells.
      Consistent with these findings, observations made in epithelial respiratory cells
      from paediatric patients with acute respiratory disease assessed that the
      expression of mDia1 is stimulated by influenza A virus but not by respiratory
      syncytial virus. Taken together, the obtained results suggest that mDia1
      restricts the initiation of influenza A/NWS/33 virus infection in LLC-MK2 cells
      by counteracting cytoskeletal dynamics.

PMID- 28744816
TI  - ACE2, CALM3 and TNNI3K polymorphisms as potential disease modifiers in
      hypertrophic and dilated cardiomyopathies.
AB  - The marked clinical and genetic heterogeneity seen in hypertrophic (HCM) and
      dilated cardiomyopathies (DCM) suggests involvement of disease modifiers and
      environmental factors in the pathophysiology of these diseases. In the current
      study, we examined association of single nucleotide polymorphisms (SNPs) of three
      candidate genes, ACE2 (rs6632677), TNNI3K (rs49812611) and CALM3 (rs13477425)
      with clinical phenotypes of HCM and DCM patients of North Indian ethnicity.
      Prevalence of ACE2 (7160726 C>G) variant genotypes (CG and GG) was significantly
      higher in DCM subjects as compared to controls. Prevalence of TNNI3K (3784 C>T)
      and CALM3 (-34T>A) variant homozygous genotype were significantly higher in HCM
      and DCM subjects as compared to controls. DCM patients with CT genotype showed
      significant decrease in LVEF as compared to CC genotype (p < 0.03). There was
      significant gene-gene interaction between these SNPs and three-way SNP
      combination of ACE2 C>G, TNN13K C>T, CALM3 A>T gene variants and was associated
      with high risk of HCM and DCM. Presence of ACE2 (7160726 C>G) and CALM3 (-34T>A)
      variant genotypes in HCM Patients with mutations (sarcomeric or non sarcomeric
      genes) was associated with increased mean septal thickness, further suggesting a
      role of these gene variants in modifying disease phenotype. Our results suggest
      that ACE2, TNNI3K and CALM3 polymorphisms are associated with increased risk of
      HCM and DCM and may act as disease modifiers of these diseases.

PMID- 28744817
TI  - Knockdown of PRMT1 suppresses IL-1beta-induced cartilage degradation and
      inflammatory responses in human chondrocytes through Gli1-mediated Hedgehog
      signaling pathway.
AB  - Osteoarthritis (OA) is characterized by articular cartilage degradation and joint
      inflammation. The purpose of the present study is to elucidate the role of the
      specific function of PRMT1 in chondrocytes and its association with the
      pathophysiology of OA. We observed that the expression of PRMT1 was apparently
      upregulated in OA cartilage, as well as in chondrocytes stimulated with IL-1beta.
      Additionally, knockdown of PRMT1 suppressed interleukin 1 beta (IL-1beta)-induced
      extracellular matrix (ECM) metabolic imbalance by regulating the expression of
      MMP-13, ADAMTS-5, COL2A1, and ACAN. Furthermore, silencing of PRMT1 dramatically
      declined the production of prostaglandin E2 (PGE2) and nitric oxide as well as
      the level of pro-inflammatory cytokine IL-6 and TNF-alpha. Mechanistic analyses
      further revealed that IL-1beta-induced activation of the Hedgehog/Gli-1 signaling
      is suppressed upon PRMT1 knockdown. However, the effects of inhibition of PRMT1
      mediated IL-1beta-induced cartilage matrix degradation and inflammatory response
      in OA chondrocytes were obviously abolished by Hedgehog agonist Purmorphamine
      (Pur). Our data collectively suggest that silencing of PRMT1 exerts anti
      catabolic and anti-inflammatory effects on IL-1beta-induced chondrocytes via
      suppressing the Gli-1 mediated Hedgehog signaling pathway, indicating that PRMT1
      plays a critical role in OA development and serves as a promising therapeutic
      target for OA.

PMID- 28744819
TI  - Advancing by retreat.

PMID- 28744818
TI  - Epigenetic modification of TLE1 induce abnormal differentiation in diabetic mice
      intestinal epithelium.
AB  - The intestinal epithelium cells (IECs) in diabetes mellitus (DM) patients have
      been proven to be abnormally differentiated. During the differentiation of IECs,
      epigenetic modification acts as an important regulator. In this study, we aimed
      to examine the epigenetic alteration of Transducin-like Enhancer of Split 1
      (TLE1), a multitask transcriptional co-repressor, contributing to the
      differentiation homeostasis in IECs of DM mice. The IECs of type 2 diabetic mice
      model were isolated and collected. Methylation states of whole genomic DNA
      promoter regions were investigated by microarray. Methylated-specific PCR was
      used to detect the methylation state of TLE1 promoter in DM mice IECs. The
      expression of TLE1, Hes1, and differentiated cell markers were measured through
      real-time PCR, Western blots, and immunohistochemistry; by transfection assay,
      TLE1 or Hes1 was independently down-regulated in intestinal epithelium cell line,
      IEC-6. Subsequent modulation on TLE1, Hes1, and differentiated intestinal cell
      markers were detected. Global gene promoter regions in DM intestinal epithelium
      were less methylated comparing to normal control. The expression of TLE1 was
      significantly increased via hypomethylated activation in DM mice IECs. Hes1 was
      significantly suppressed and the terminal cell markers abnormally expressed in DM
      mice IECs (P < 0.05). Inhibition or induction on the abundance of TLE1 in IEC-6
      cell line resulted in the corresponding dysregulation of Hes1 and intestinal
      epithelium differentiation (P < 0.05). Demethylation of TLE1 promoter region
      activates the self-expression in diabetic mice IECs. Subsequently, TLE1, through
      the transcriptional suppression on expression of Hes1, contributes to the
      aberrant differentiation of IECs in DM mice.

PMID- 28744820
TI  - Dedicated cardiac CZT SPECT is steadily moving to achieve its destiny.

PMID- 28744821
TI  - Evaluating the effect of instruction and practice schedule on the acquisition of
      ECG interpretation skills.
AB  - INTRODUCTION: Evidence of the benefit of distributed instruction and interleaved
      practice comes from studies using simple materials (e. g. word pairs).
      Furthermore, there is currently no evidence of the combined impact of these
      strategies in undergraduate medical education. The present study evaluated the
      impact of varying both instruction and practice schedules for the acquisition of
      ECG interpretation skills. METHODS: We conducted a 2 * 2 factorial study with two
      levels of instruction (massed and distributed) and two levels of practice
      (interleaved and blocked). A three-module introductory course in ECG
      interpretation was delivered to 80 first year medical undergraduate students.
      Students were assigned to one of four Instruction-Practice conditions: Massed
      Interleaved, Massed-Blocked, Distributed-Interleaved and Distributed-Blocked.
      Learning was evaluated by a multiple choice quiz at the end of each module and a
      final multiple choice quiz at the end of the course. RESULTS: End of module mean
      scores showed that distributed instruction was consistently superior to massed
      instruction (52% vs 42%, p < 0.01). However, there was no effect of practice and
      no interaction between teaching and practice methods. The delayed final test
      scores revealed an advantage for blocked over mixed practice (34% vs 24%, p <
      0.05) and distributed over massed instruction (34% vs 24%, p < 0.05). DISCUSSION:
      These results suggest that these popular strategies may have varying effects with
      complex learning materials. Further research is required to understand how these
      strategies affect the learning of simple and very complex skills.

PMID- 28744822
TI  - Magnitude and direction of the association between Clostridium difficile
      infection and proton pump inhibitors in adults and pediatric patients: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is a cause of increased
      morbidity and health care costs among hospitalized patients. Proton pump
      inhibitors (PPIs) are mainly used for the treatment of acid-related upper
      gastrointestinal diseases. The aim of the study was to assess the risks
      associated with initial and recurrent CDI in adult and pediatric patients treated
      with PPIs. METHODS: A systematic search was performed using PubMed (Medline),
      Embase, and Web of Science with the following search terms: ("proton pump
      inhibitor," "PPI," or "acid suppression") AND ("infection," "diarrhea,"
      "diarrhoea," "colitis," or "disease") AND ("Clostridium difficile"). Meta
      analysis was performed using Revman5.3 software. Pooled odds ratios (ORs)
      presented as standard plots with 95% confidence intervals (CIs) were determined.
      RESULTS: Sixty-seven eligible studies were selected. PPI use was significantly
      associated with risk of CDI (OR 2.34, 95% CI 1.94-2.82; P < 0.00001). Pooled data
      from twelve studies demonstrated a significant association between PPI use and
      recurrent CDI (OR 1.73, 95% CI 1.39-2.15; P = 0.02). Subgroup analysis revealed
      significant associations between PPI use and an increased incidence of CDI among
      adult (OR 2.30, 95% CI 1.89-2.80; P < 0.00001) and pediatric (OR 3.00, 95% CI
      1.44-6.23; P < 0.00001) patients. CONCLUSIONS: PPI use was associated with CDI in
      adult and pediatric patients, and with recurrent CDI. Although many risk factors
      are associated with the occurrence and recurrence of CDI, consideration should be
      given to not administering PPIs at any age if they are unnecessary.

PMID- 28744823
TI  - Combination of PNPLA3 and TLL1 polymorphism can predict advanced fibrosis in
      Japanese patients with nonalcoholic fatty liver disease.
AB  - BACKGROUND: Hepatic fibrosis is an independent risk factor for mortality and
      liver-related events in patients with nonalcoholic fatty liver disease (NAFLD).
      PNPLA3 rs738409 has been associated with fibrosis in viral and non-viral
      hepatitis. TLL1 rs17047200 also has been associated with developing
      hepatocellular carcinoma probably via hepatic fibrogenesis. We estimated the
      impact of these genetic polymorphisms on hepatic fibrosis in Japanese patients
      with NAFLD. METHODS: We analyzed the association between these genetic variants
      and the backgrounds of 817 individuals who received health checkups (health check
      cohort) from 2012 to 2014. Then, we investigated the relationship between genetic
      variants and liver histology in 258 consecutive patients with biopsy-proven NAFLD
      in Japan (NAFLD cohort) from 2012 to 2017 (UMIN000027399). RESULTS: The
      prevalence of PNPLA3 CG/GG in the NAFLD cohort was higher than that in the health
      check cohort (p < 0.001). The prevalence of patients with advanced fibrosis
      (stages 3-4) was higher for PNPLA3 genotype CG/GG than CC (p = 0.048) and for
      TLL1 genotype AT/TT than AA (p = 0.044). The high-risk group which had at least
      two risk alleles of these variants was more likely to have advanced fibrosis (p =
      0.004). Multivariate analysis identified body mass index [odds ratio (OR) 1.123,
      serum AST (OR 1.037, p = 0.004], serum albumin (OR 0.247, p = 0.032), and genetic
      high risk (OR 2.632, p = 0.026) as predictors of advanced fibrosis. CONCLUSIONS:
      In Japanese patients with NAFLD, individuals with risk alleles of PNPLA3 and TLL1
      may have a risk of advanced fibrosis.

PMID- 28744824
TI  - Erratum to: Virological and Clinical Characteristics of Hepatitis B Virus
      Genotype A.

PMID- 28744825
TI  - Erratum to: Hemispheric activation differences in novice and expert clinicians
      during clinical decision making.

PMID- 28744826
TI  - Erratum to: Working memory, reasoning, and expertise in medicine-insights into
      their relationship using functional neuroimaging.

PMID- 28744827
TI  - Mortality and morbidity from infectious disease in the Egyptian Expeditionary
      Force (1916-1918).

PMID- 28744829
TI  - Early initiation of chemoradiation following index craniotomy is associated with
      decreased survival in high-grade glioma.
AB  - The Stupp protocol of post-resection external beam radiation therapy and
      concomitant temozolomide is the standard of care for patients with newly
      diagnosed glioblastoma, with expanded use in anaplastic astrocytoma. However, the
      optimal interval between surgery and these adjuvant therapies, and its impact on
      survival, is unknown. To investigate this, de-identified claims from a large,
      private health insurance database were queried to identify adult patients who
      underwent index craniotomy for resection of a supratentorial neoplasm during the
      period 2005-2014 and began postoperative radiation and temozolomide within 13
      weeks of surgery. A total of 2535 patients were assigned to groups based on
      interval from surgery to first radiation treatment of up to 4 weeks, 4-6 weeks,
      or 6-13 weeks. Of these, 1098 patients began radiation treatment within 4 weeks
      of craniotomy, 1019 between 4 and 6 weeks, and 418 between 6 and 13 weeks. There
      was significant regional variation in treatment schedule in the United States.
      Survival was calculated based on time from first craniotomy to death. Kaplan
      Meier plot and multivariate Cox proportional hazard regression demonstrated a
      statistically significant association between earliest postoperative radiation
      and decreased survival (hazard ratio 1.31), along with older age and male sex.
      Earlier initiation of postoperative radiation for high-grade glioma is not
      associated with increased survival. Rather, beginning radiation treatment within
      4 weeks of craniotomy was associated with significantly worse survival compared
      to initiation of treatment 4-13 weeks after craniotomy. This is the largest
      population-based study to date regarding timing of Stupp protocol initiation.

PMID- 28744828
TI  - Review of numerical methods for simulation of mechanical heart valves and the
      potential for blood clotting.
AB  - Even though the mechanical heart valve (MHV) has been used routinely in clinical
      practice for over 60 years, the occurrence of serious complications such as blood
      clotting remains to be elucidated. This paper reviews the progress that has been
      made over the years in terms of numerical simulation method and the contribution
      of abnormal flow toward blood clotting from MHVs in the aortic position. It is
      believed that this review would likely be of interest to some readers in various
      disciplines, such as engineers, scientists, mathematicians and surgeons, to
      understand the phenomenon of blood clotting in MHVs through computational fluid
      dynamics.

PMID- 28744830
TI  - Dabrafenib for cutaneous melanoma infiltrating the vitreous: regression of
      metastasis and occurrence of uveitis as a secondary effect.
AB  - Intraocular metastasis of cutaneous melanoma is extremely infrequent. This
      typically occurs in advanced metastatic disease and has a poor survival
      prognosis. The most frequent reported treatment is radiotherapy. BRAF inhibitors
      are new, orally administered and very effective drugs used for metastatic
      cutaneous melanoma. Herein, we report a case of a 58-year-old patient with a
      recent diagnosis of cutaneous melanoma who consulted for floaters and presented
      vitreous opacities in both eyes. A diagnostic vitrectomy of his left eye was
      performed and pathologic analysis disclosed infiltrating melanoma cells in the
      vitreous. Treatment with dabrafenib (a type of BRAF inhibitor) achieved the
      regression of the intraocular metastasis in the right eye. Moreover, the patient
      presented a severe anterior uveitis due to dabrafenib, a well-known secondary
      effect of this drug.

PMID- 28744831
TI  - 25-Hydroxyvitamin D levels of children are inversely related to adiposity
      assessed by body mass index.
AB  - Vitamin D deficiency is associated with wide range of pathologies. Some evidences
      have shown that low vitamin D circulating levels in children and adolescent are
      related to fat mass and obesity. The objectives of the present study were to
      characterize vitamin D status in children and adolescents and to determine if
      serum 25-hydroxyvitamin D (25(OH)D) concentration is related to adiposity
      assessed by body mass index (BMI). Serum 25(OH)D levels were measured by LIAISON
      method in 471 children and adolescents (2 to 18 years age) and analyzed according
      to gender, pubertal period, age, and BMI. An overall prevalence of 25(OH)D
      insufficiency and deficiency was present in the 67.1%. Lower 25(OH)D levels were
      found in females (25.56 +/- 14.03 vs 29.71 +/- 17.10 ng ml-1; P = 0.004) and
      pubertal children (25.52 +/- 13.97 vs 29.21 +/- 16.83 ng ml-1; P = 0.011). In
      addition, an inverse relation of BMI and age on 25(OH)D concentrations was
      observed in children. In conclusion, low vitamin D status was highly prevalent
      among children and adolescents. Of note, a non-lineal regression model showed
      that 39.6% of vitamin D levels variability was explained by BMI. These results
      indicate that adiposity assessed by BMI impacts vitamin D status.

PMID- 28744832
TI  - Isolation and Selection of Potential Probiotic Bacteria from the Pig
      Gastrointestinal Tract.
AB  - The present study aimed to isolate bacterial strains from the pig
      gastrointestinal tract that have antagonistic activity against potential
      pathogens and are able to produce antimicrobial compounds. That ability would be
      a first requirement for the strains' possible use as probiotics. Samples obtained
      from pig intestinal mucosa and contents were screened for the presence of
      antagonistic activity against pathogenic indicator strains of Escherichia coli,
      Salmonella, and Listeria by means of the double-layer technique. Samples
      displaying the largest inhibitory halos were further studied for the production
      of inhibitory substances using the agar diffusion and microtitration methods. The
      three most promising isolates were identified by sequencing of the 16S rRNA gene
      and showed highest affiliation to Lactobacillus salivarius. Optimal growth
      conditions and bacteriocin production were recorded in de Man, Rogosa, and Sharpe
      broth under anaerobic conditions at 37  degrees C. The antimicrobial substances
      were found to be sensitive to proteolytic enzymes but showed good stability at pH
      values below 6. Our findings suggest that these three intestinal strains are able
      to produce antimicrobial substances capable of inhibiting the growth of potential
      enteric pathogens and might have potential as probiotic feed additives for the
      prevention of gastrointestinal diseases.

PMID- 28744833
TI  - Evaluation of In Vivo Probiotic Efficiency of Bacillus amyloliquefaciens in Labeo
      rohita Challenged by Pathogenic Strain of Aeromonas hydrophila MTCC 1739.
AB  - Diseases in aquatic organisms, including fish, are a major concern in aquaculture
      production. In this present investigation, we have evaluated the beneficial
      effects of dietary Bacillus amyloliquefaciens CCF7 (GenBank Acc. No. KP256501)
      supplementation in rohu (Labeo rohita) challenged by a pathogenic strain of
      Aeromonas hydrophila MTCC 1739. Four experimental diets were formulated: control
      diet (no probiotics) and three experimental diets (different concentrations of
      probiotic candidate B. amyloliquefaciens CCF7 at 105 (T1), 107 (T2), 109 (T3)
      CFU/g). Further, we have divided the feeding trial into pre-challenge (70 days)
      and post-challenge (28 days) periods and various immune parameters (serum
      protein, globulin, albumin, lysozyme, and IgM), and stress parameters
      (malondialdehyde, catalase, and superoxide dismutase) were examined during both
      the periods. Throughout the entire experiment, control group was fed with
      probiotic free basal diet, while the treatment groups received probiotic
      supplemented diets (PSD). After challenge test, serum aspartate transaminase
      (AST), serum alanine transaminase (ALT) activity, and liver malondialdehyde level
      have increased significantly in control groups; however, level of these
      parameters were considerably lower in fish fed with PSD. In contrast, liver
      catalase and superoxide dismutase activities and serum globulin concentration was
      significantly higher in the group fed with T3 diet followed by T2. Furthermore,
      an elevated level of serum IgM and higher activity of serum lysozyme was also
      recorded in PSD fed groups, especially for T3 group which confirmed the probiotic
      efficiency of the bacterium B. amyloliquefaciens CCF7. We strongly believe that
      B. amyloliquefaciens CCF7 will be a good probiotic candidate in aquaculture
      industries.

PMID- 28744834
TI  - Extra-adrenal glucocorticoids contribute to the postprandial increase of
      circulating leptin in mice.
AB  - Leptin, an adipokine secreted by white adipocytes, is known for its function in
      regulating food intake and energy expenditure, but the mechanisms regulating its
      circulating levels is not fully understood. Our previous findings suggest that as
      yet unidentified humoral factors released from enterocytes are involved. The
      present study tested glucocorticoids (GCs) as candidate factors. Supplementation
      of corticosterone and cortisol promoted leptin production in murine adipocytes
      from the 3T3-L1 cell strain and human adipocytes from the Simpson Golabi-Behmel
      syndrome (SGBS) cell strain, respectively. These changes were observed in the
      absence but not presence of the GC-receptor antagonist mifepristone. The cortisol
      concentration in conditioned medium (CM) of human enterocyte-like Caco-2 cells
      was increased by phorbol-12-myristate 13-acetate and decreased by metyrapone.
      When SGBS adipocytes were cultured in these CMs, leptin production was positively
      associated with cortisol concentrations. During a 2-h refeeding after fasting,
      plasma leptin levels continued to increase in sham-operated mice, transiently
      increased at 60 min in adrenalectomized mice, and were unchanged in mifepristone
      administered mice. These results suggest that extra-adrenal GCs contribute to the
      GC-receptor signaling-dependent increase of postprandial circulating leptin,
      whereas further studies will be required to determine whether enterocytes
      participate in the GCs-mediated increase of postprandial circulating leptin.

PMID- 28744835
TI  - Advantages of Laparoscopic Radiofrequency Ablation Over Percutaneous
      Radiofrequency Ablation in Hepatocellular Carcinoma.
AB  - BACKGROUND: Inoperable hepatocellular carcinoma (HCC) can be treated with
      laparoscopic radiofrequency ablation (LRFA), which is generally a more accurate
      and accessible procedure than percutaneous RFA (PRFA). However, few studies have
      compared survival outcomes between LRFA and PRFA in patients with HCC. AIMS: This
      study aimed to compare the efficacy of LRFA and PRFA for HCC treatment. METHODS:
      Patients who underwent PRFA or LRFA as an initial treatment modality between
      April 2005 and April 2016 were enrolled in this study. The overall and recurrence
      free survival rates were examined for each patient. Additionally, propensity
      score matching was performed for both groups. RESULTS: The baseline
      characteristics of patients in the PRFA and LRFA groups showed several minor
      differences. Multivariate analysis showed that the RFA method was not a critical
      determinant of recurrence-free or overall survival (p = 0.069 and p = 0.406).
      Among patients who underwent RFA as the initial treatment modality, there was no
      significant effect between either RFA procedures on survival. After propensity
      score matching, univariate analysis showed a significant difference in overall
      survival between PRFA and LRFA (p = 0.031). Multivariate analysis showed that
      LRFA is a strong factor that contributed to an improved overall survival in HCC
      patients (hazard ratio 0.108, p = 0.040). Furthermore, our data showed that LRFA
      was able to limit multiple intrahepatic recurrences, as well as prevent marginal
      recurrence. CONCLUSIONS: LRFA appears to be superior to PRFA in terms of
      survival. LRFA may help reduce mortality in HCC patients.

PMID- 28744836
TI  - Liver Transplantation for Nonalcoholic Steatohepatitis in the US: Temporal Trends
      and Outcomes.
AB  - BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is a rapidly growing
      etiology of end-stage liver disease in the US. Temporal trends and outcomes in
      NASH-related liver transplantation (LT) in the US were studied. METHODS: A
      retrospective cohort study utilizing the United Network for Organ Sharing and
      Organ Procurement and Transplantation (UNOS/OPTN) 2003-2014 database was
      conducted to evaluate the frequency of NASH-related LT. Etiology-specific post
      transplant survival was evaluated with Kaplan-Meier methods and multivariate Cox
      proportional hazards models. RESULTS: Overall, 63,061 adult patients underwent LT
      from 2003 to 2014, including 20,782 HCV (32.96%), 9470 ALD (15.02%), and 8262
      NASH (13.11%). NASH surpassed ALD and became the second leading indication for LT
      beginning in 2008, accounting for 17.38% of LT in 2014. From 2003 to 2014, the
      number of LT secondary to NASH increased by 162%, whereas LT secondary to HCV
      increased by 33% and ALD increased by 55%. Due to resurgence in ALD, the growth
      in NASH and ALD was comparable from 2008 to 2014 (NASH +50.15% vs. ALD +41.87%).
      The post-transplant survival in NASH was significantly higher compared to HCV (5
      year survival: NASH -77.81%, 95% CI 76.37-79.25 vs. HCV -72.15%, 95% CI 71.37
      72.93, P < .001). In the multivariate Cox proportional hazards model, NASH
      demonstrated significantly higher post-transplant survival compared to HCV (HR
      0.75; 95% CI 0.71-0.79, P < .001). CONCLUSIONS: Currently, NASH is the most
      rapidly growing indication for LT in the US. Despite resurgence in ALD, NASH
      remains the second leading indication for LT.

PMID- 28744837
TI  - Guest editorial of the IJCARS MICCAI 2016 special issue.

PMID- 28744838
TI  - Effects of Hydroxyurea Exposure on the Rat Cerebellar Neuroepithelium: an
      Immunohistochemical and Electron Microscopic Study Along the Anteroposterior and
      Mediolateral Axes.
AB  - We present a histological study of the cell death of cerebellar neuroepithelial
      neuroblasts following treatment with the cytotoxic agent hydroxyurea (HU) during
      the embryonic life. Pregnant rats were treated with a single dose of HU (300
      mg/kg) at embryonic days 13, 14, or 15 of gestation, and their fetuses were
      studied from 5 to 35 h after treatment to elucidate the mechanisms of HU-induced
      fetotoxicity. Quantification of several parameters such as the density of
      pyknotic, mitotic, and PCNA-immunoreactive cells indicated that HU compromises
      the survival of the cerebellar neuroepithelium neuroblasts. On the other hand,
      our light and electron microscopic investigations during the course of prenatal
      development indicated that HU leads to two types of cell death: apoptosis and
      cells presenting cytoplasmic vacuolization, altered organelles, and a
      recognizable cell nucleus. Both modalities of cell death resulted in a
      substantial loss of cerebellar neuroepithelium cells. Current results suggest
      that HU exposure during gestation is toxic to the cerebellar neuroepithelium.
      Moreover, they allow to examine the mechanisms of HU-induced toxicity during the
      early development of the central nervous system. Our data also suggest that it is
      essential to avoid underestimating the adverse effects of HU when administered
      during early prenatal life.

PMID- 28744839
TI  - Methodology to Produce Specimen-Specific Models of Vertebrae: Application to
      Different Species.
AB  - Image-based continuum-level finite element models have been used for bones to
      evaluate fracture risk and the biomechanical effects of diseases and therapies,
      capturing both the geometry and tissue mechanical properties. Although models of
      vertebrae of various species have been developed, an inter-species comparison has
      not yet been investigated. The purpose of this study was to derive species
      specific modelling methods and compare the accuracy of image-based finite element
      models of vertebrae across species. Vertebral specimens were harvested from
      porcine (N = 12), ovine (N = 13) and bovine (N = 14) spines. The specimens were
      experimentally loaded to failure and apparent stiffness values were derived.
      Image-based finite element models were generated reproducing the experimental
      protocol. A linear relationship between the element grayscale and elastic modulus
      was calibrated for each species matching in vitro and in silico stiffness values,
      and validated on independent sets of models. The accuracy of these relationships
      were compared across species. Experimental stiffness values were significantly
      different across species and specimen-specific models required species-specific
      linear relationship between image grayscale and elastic modulus. A good agreement
      between in vitro and in silico values was achieved for all species, reinforcing
      the generality of the developed methodology.

PMID- 28744840
TI  - Organ Dynamics and Fluid Dynamics of the HH25 Chick Embryonic Cardiac Ventricle
      as Revealed by a Novel 4D High-Frequency Ultrasound Imaging Technique and
      Computational Flow Simulations.
AB  - Past literature has provided evidence that a normal mechanical force environment
      of blood flow may guide normal development while an abnormal environment can lead
      to congenital malformations, thus warranting further studies on embryonic
      cardiovascular flow dynamics. In the current study, we developed a non-invasive
      4D high-frequency ultrasound technique, and use it to analyze cardiovascular
      organ dynamics and flow dynamics. Three chick embryos at stage HH25 were scanned
      with high frequency ultrasound in cine-B-mode at multiple planes spaced at 0.05
      mm. 4D images of the heart and nearby arteries were generated via temporal and
      spatial correlation coupled with quadratic mean ensemble averaging. Dynamic mesh
      CFD was performed to understand the flow dynamics in the ventricle of the 2
      hearts. Our imaging technique has sufficiently high resolution to enable organ
      dynamics quantification and CFD. Fine structures such as the aortic arches and
      details such as the cyclic distension of the carotid arteries were captured. The
      outflow tract completely collapsed during ventricular diastole, possible serving
      the function of a valve to prevent regurgitation. CFD showed that ventricular
      wall shear stress (WSS) were in the range of 0.1-0.5 Pa, and that the left side
      of the common ventricle experienced lower WSS than the right side. The pressure
      gradient from the inlet to the outlet of the ventricle was positive over most of
      the cardiac cycle, and minimal regurgitation flow was observed, despite the
      absence of heart valves. We developed a new image-based CFD method to elucidate
      cardiac organ dynamics and flow dynamics of embryonic hearts. The embryonic heart
      appeared to be optimized to generate net forward flow despite the absence of
      valves, and the WSS environment appeared to be side-specific.

PMID- 28744841
TI  - Cell Mechanosensors and the Possibilities of Using Magnetic Nanoparticles to
      Study Them and to Modify Cell Fate.
AB  - The use of magnetic nanoparticles (MNPs) is a promising technique for future
      advances in biomedical applications. This idea is supported by the availability
      of MNPs that can target specific cell components, the variety of shapes of MNPs
      and the possibility of finely controlling the applied magnetic forces. To examine
      this opportunity, here we review the current developments in the use of MNPs to
      mechanically stimulate cells and, specifically, the cell mechanotransduction
      systems. We analyze the cell components that may act as mechanosensors and their
      effect on cell fate and we focus on the promising possibilities of controlling
      stem-cell differentiation, inducing cancer-cell death and treating nervous-system
      diseases.

PMID- 28744842
TI  - The Quantitative Structural and Compositional Analyses of Degenerating
      Intervertebral Discs Using Magnetic Resonance Imaging and Contrast-Enhanced Micro
      Computed Tomography.
AB  - The intervertebral disc (IVD) is susceptible to degenerative changes that are
      associated with low back pain. Murine models are often used to investigate the
      mechanistic changes in the development, aging, and diseased states of the IVD,
      yet the detection of early degenerative changes in structure is challenging
      because of the minute size of the murine IVDs. Histology is the gold standard for
      examining the IVD structure, but it is susceptible to sectioning artifacts,
      spatial biases, and requires the destructive preparation of the sample. We have
      previously demonstrated the feasibility of using Ioversol for the contrast
      enhanced micro-computed tomography (microCT) to visualize and quantitate the
      intact healthy murine IVD. In this work, we demonstrate utility of this approach
      to monitor the longitudinal changes of in vitro nucleolytic- and mechanical
      injury- degeneration models of the murine discs and introduce novel quantitative
      metrics to characterize the structure and composition of the IVD. Moreover, we
      compared the imaging quality and quantitation of these in vitro models to
      magnetic resonance imaging (MRI) and histology. Stab puncture, trypsin injection,
      and collagenase injection all induced detectable and significant changes in
      structure and composition of the discs overtime. Compared to MRI and histology,
      contrast-enhanced microCT produced superior images that capture the degenerative
      progression in these models. Contrast-enhanced microCT was also capable of
      monitoring the structural deteriorations via the changes in disc height and
      volume, and novel the nucleus pulposus intensity/disc intensity (NI/DI) parameter
      provides a surrogate measure of proteoglycan composition (R = 0.96). Overall,
      this approach allows for the nondestructive monitoring of the structure and
      composition of the IVD at very high resolutions.

PMID- 28744844
TI  - Suspected Adverse Effects After Human Papillomavirus Vaccination: A Temporal
      Relationship Between Vaccine Administration and the Appearance of Symptoms in
      Japan.
AB  - INTRODUCTION: In Japan, after receiving human papillomavirus vaccination, a
      significant number of adolescent girls experienced various symptoms, the vast
      majority of which have been ascribed to chronic regional pain syndrome,
      orthostatic intolerance, and/or cognitive dysfunction. However, a causal link has
      not been established between human papillomavirus vaccination and the development
      of these symptoms. OBJECTIVE: The aim of this study was to clarify the temporal
      relationship between human papillomavirus vaccination and the appearance of post
      vaccination symptoms. METHODS: Between June 2013 and December 2016, we examined
      symptoms and objective findings in 163 female patients who had received human
      papillomavirus vaccination. We used newly defined diagnostic criteria for
      accurate inclusion of patients who experienced adverse symptoms after human
      papillomavirus vaccination; these diagnostic criteria were created for this
      study, and thus their validity and reliability have not been established.
      RESULTS: Overall, 43 female patients were excluded. Among the remaining 120
      patients, 30 were diagnosed as having definite vaccine-related symptoms, and 42
      were diagnosed as probable. Among these 72 patients, the age at initial
      vaccination ranged from 11 to 19 years (average 13.6 +/- 1.6 years), and the age
      at appearance of symptoms ranged from 12 to 20 years (average 14.4 +/- 1.7
      years). The patients received the initial human papillomavirus vaccine injection
      between May 2010 and April 2013. The first affected girl developed symptoms in
      October 2010, and the last two affected girls developed symptoms in October 2015.
      The time to onset after the first vaccine dose ranged from 1 to 1532 days
      (average 319.7 +/- 349.3 days). CONCLUSIONS: The period of human papillomavirus
      vaccination considerably overlapped with that of unique post-vaccination symptom
      development. Based on these sequential events, it is suggested that human
      papillomavirus vaccination is related to the transiently high prevalence of the
      previously mentioned symptoms including chronic regional pain syndrome and
      autonomic and cognitive dysfunctions in the vaccinated patients.

PMID- 28744845
TI  - Drug-Induced Dental Caries: A Disproportionality Analysis Using Data from
      VigiBase.
AB  - INTRODUCTION: Dental caries is defined as a pathological breakdown of the tooth.
      It is an infectious phenomenon involving a multifactorial aetiology. The impact
      of drugs on cariogenic risk has been poorly investigated. OBJECTIVES: In this
      study, we identified drugs suspected to induce dental caries as adverse drug
      reactions (ADRs) and then studied a possible pathogenic mechanism for each drug
      that had a statistically significant disproportionality. METHODS: We extracted
      individual case safety reports of dental caries associated with drugs from
      VigiBase(r) (the World Health Organization global individual case safety report
      database). We calculated disproportionality for each drug with a reporting odds
      ratio (ROR) and 99% confidence interval. We analysed the pharmacodynamics of each
      drug that had a statistically significant disproportionality. RESULTS: In
      VigiBase(r), 5229 safety reports for dental caries concerning 733 drugs were
      identified. Among these drugs, 88 had a significant ROR, and for 65 of them
      (73.9%), no information about dental caries was found in the summaries of the
      product characteristics, the Micromedex(r) DRUGDEX, or the Martindale databases.
      Regarding the pharmacological classes of drugs involved in dental caries, we
      identified bisphosphonates, atropinic drugs, antidepressants, corticoids,
      immunomodulating drugs, antipsychotics, antiepileptics, opioids and beta2
      adrenoreceptor agonist drugs. Regarding possible pathogenic mechanisms for these
      drugs, we identified changes in salivary flow/composition for 54 drugs (61.4%),
      bone metabolism changes for 31 drugs (35.2%), hyperglycaemia for 32 drugs (36.4%)
      and/or immunosuppression for 23 drugs (26.1%). For nine drugs (10.2%), the
      mechanism was unclear. CONCLUSION: We identified 88 drugs with a significant
      positive disproportionality for dental caries. Special attention has to be paid
      to bisphosphonates, atropinic drugs, immunosuppressants and drugs causing
      hyperglycaemia.

PMID- 28744846
TI  - Extubation Failure and Tracheostomy Placement in Children with Acute
      Neurocritical Illness.
AB  - BACKGROUND: There is a lack of data describing the risk factors for extubation
      failure (EF) or tracheostomy placement in pediatric neurocritical care (NCC)
      patients. METHODS: A retrospective chart review of children admitted to the
      pediatric intensive care unit who were intubated for >24 h with an acute
      neurocritical illness and had an extubation attempt. Bivariate and multivariate
      statistical analysis was performed to determine significant associations of
      demographic, neurologic, pulmonary, and clinical variables with EF and
      tracheostomy placement. Analysis of predictive factors for EF (within 48 h) and
      tracheostomy placement during the hospitalization was conducted on a first
      extubation attempt group (n = 193) and a second attempt group (n = 23) who
      experienced either EF or a "late re-intubation" (>48 h-7 days). RESULTS:
      Traumatic brain injury (37.3%) and seizures/status epilepticus (31.4%) were the
      most common diagnoses with neuromuscular weakness patients having the highest
      risk for EF and tracheostomy placement. EF occurred in 20/193 (10.4%) patients
      after their first attempt and 6/23 (26.1%) after a second attempt. Compared to
      those with a fair/strong cough, patients with a weak/absent cough had a relative
      risk (RR) of 9.4 for EF (95% CI, 4.9-17.9, p < 0.001) and 6.7 (95% CI, 2.3-18.9,
      p = 0.01) for tracheostomy placement on the first and second attempts,
      respectively. Glasgow Coma Score (GCS), endotracheal tube (ETT) secretion
      characteristics, and pulmonary variables were not associated with EF or
      tracheostomy placement. CONCLUSIONS: A weak/absent cough reflex is associated
      with an increased risk of failing extubation and placement of a tracheostomy in
      intubated pediatric NCC patients.

PMID- 28744847
TI  - Factors Considered by Clinicians when Prognosticating Intracerebral Hemorrhage
      Outcomes.
AB  - BACKGROUND: The early subjective clinical judgment of clinicians outperforms
      formal prognostic scales for accurate determination of outcome after
      intracerebral hemorrhage (ICH), with the judgment of physicians and nurses having
      equivalent accuracy. This study assessed specific decisional factors that
      physicians and nurses incorporate into early predictions of functional outcome.
      METHODS: This prospective observational study enrolled 121 ICH patients at five
      US centers. Within 24 h of each patient's admission, one physician and one nurse
      on the clinical team were each surveyed to predict the patient's modified Rankin
      Scale (mRS) at 3 months and to list up to 10 subjective factors used in
      prognostication. Factors were coded and compared between (1) physician and nurse
      and (2) accurate and inaccurate surveys, with accuracy defined as an exact
      prediction of mRS. RESULTS: Aside from factors that are components of the ICH or
      FUNC scores, surveys reported pre-existing comorbidities (40.0%), other clinical
      or radiographic factors not in clinical scales (43.0%), and non
      clinical/radiographic factors (21.9%) as important. Compared to physicians,
      nurses more frequently listed neurologic examination components (Glasgow Coma
      Scale motor, 27.3 vs. 5.8%, p < 0.0001; GCS verbal, 12.4 vs. 0.0%, p < 0.0001)
      and non-clinical/radiographic factors (31.4 vs. 12.4%, p = 0.0005). Physicians
      more frequently listed neuroimaging factors (ICH location, 33.9 vs. 7.4%, p <
      0.0001; intraventricular hemorrhage, 13.2 vs. 2.5%, p = 0.003). There was no
      difference in listed factors between accurate versus inaccurate surveys.
      CONCLUSIONS: Clinicians frequently utilize factors outside of the components of
      clinical scales for prognostication, with physician and nurses focusing on
      different factors despite having similar accuracy.

PMID- 28744848
TI  - Systems and precision medicine approaches to diabetes heterogeneity: a Big Data
      perspective.
AB  - Big Data, and in particular Electronic Health Records, provide the medical
      community with a great opportunity to analyze multiple pathological conditions at
      an unprecedented depth for many complex diseases, including diabetes. How can we
      infer on diabetes from large heterogeneous datasets? A possible solution is
      provided by invoking next-generation computational methods and data analytics
      tools within systems medicine approaches. By deciphering the multi-faceted
      complexity of biological systems, the potential of emerging diagnostic tools and
      therapeutic functions can be ultimately revealed. In diabetes, a multidimensional
      approach to data analysis is needed to better understand the disease conditions,
      trajectories and the associated comorbidities. Elucidation of multidimensionality
      comes from the analysis of factors such as disease phenotypes, marker types, and
      biological motifs while seeking to make use of multiple levels of information
      including genetics, omics, clinical data, and environmental and lifestyle
      factors. Examining the synergy between multiple dimensions represents a
      challenge. In such regard, the role of Big Data fuels the rise of Precision
      Medicine by allowing an increasing number of descriptions to be captured from
      individuals. Thus, data curations and analyses should be designed to deliver
      highly accurate predicted risk profiles and treatment recommendations. It is
      important to establish linkages between systems and precision medicine in order
      to translate their principles into clinical practice. Equivalently, to realize
      their full potential, the involved multiple dimensions must be able to process
      information ensuring inter-exchange, reducing ambiguities and redundancies, and
      ultimately improving health care solutions by introducing clinical decision
      support systems focused on reclassified phenotypes (or digital biomarkers) and
      community-driven patient stratifications.

PMID- 28744849
TI  - Response to "PNPLA3 rs738409 and Hepatotoxicity in Children With B-cell Acute
      Lymphoblastic Leukemia: A Validation Study in a Spanish Cohort".

PMID- 28744850
TI  - The expression of hematopoietic progenitor cell antigen CD34 is regulated by DNA
      methylation in a site-dependent manner in gastrointestinal stromal tumours.
AB  - The anatomic site-dependent expression of hematopoietic progenitor cell antigen
      CD34 is a feature of gastrointestinal stromal tumours (GISTs). The basis for the
      differential CD34 expression is only incompletely understood. This study aimed at
      understanding the regulation of CD34 in GISTs and clarification of its site
      dependent expression. Two sample sets of primary GISTs were interrogated
      including 52 fresh-frozen and 134 paraffin-embedded and formalin-fixed specimens.
      DNA methylation analysis was performed by HumanMethylation450 BeadChip array in
      three cell lines derived from gastric and intestinal GISTs, and differentially
      methylated CpG sites were established upstream of CD34. The methylation degree
      was further quantified by pyrosequencing, and inverse correlation with CD34 mRNA
      and protein abundance was revealed. The gene's expression could be activated upon
      induction of DNA hypomethylation with 5-aza-2'-deoxycytidine in GIST-T1 cells. In
      patient samples, a strong inverse correlation of DNA methylation degree with
      immunohistochemically evaluated CD34 expression was documented. Both CD34
      expression and DNA methylation levels were specific to the tumours' anatomic
      location and mutation status. A constant decrease in methylation levels was
      observed ranging from almost 100% hypermethylation in intestinal GISTs from
      duodenum to hypomethylation in rectum. CD34 was heavily methylated in gastric
      PDGFRA-mutant GISTs in comparison to hypomethylated KIT-mutant counterparts. Next
      to CD34 hypermethylation, miR-665 was predicted and experimentally confirmed to
      target CD34 mRNA in GIST-T1 cells. Our results suggest that CD34 expression in
      GISTs may undergo a complex control by DNA methylation and miR-665. Differential
      methylation and expression of CD34 in GISTs along the gastrointestinal tract axis
      and in tumours that harbour different gain-of-function mutations suggest the
      origin from different cell populations in the gastrointestinal tract.

PMID- 28744851
TI  - Post-translational regulation of antiviral innate signaling.
AB  - The innate immune system initiates immune responses by pattern-recognition
      receptors (PRR). Virus-derived nucleic acids are sensed by the retinoic acid
      inducible gene I (RIG-I)-like receptor (RLR) family and the toll-like receptor
      (TLR) family as well as the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS).
      These receptors activate IRF3/7 and NF-kappaB signaling pathways to induce the
      expression of type I interferons (IFNs) and other cytokines firing antiviral
      responses within the cell. However, to achieve a favorable outcome for the host,
      a balanced production of IFNs and activation of antiviral responses is required.
      Post-translational modifications (PTMs), such as the covalent linkage of
      functional groups to amino acid chains, are crucial for this immune homeostasis
      in antiviral responses. Canonical PTMs including phosphorylation and
      ubiquitination have been extensively studied and other PTMs such as methylation,
      acetylation, SUMOylation, ADP-ribosylation and glutamylation are being
      increasingly implicated in antiviral innate immunity. Here we summarize our
      recent understanding of the most important PTMs regulating the antiviral innate
      immune response, and their role in virus-related immune pathogenesis.

PMID- 28744852
TI  - Phenomenological network models: Lessons for epilepsy surgery.
AB  - The current opinion in epilepsy surgery is that successful surgery is about
      removing pathological cortex in the anatomic sense. This contrasts with recent
      developments in epilepsy research, where epilepsy is seen as a network disease.
      Computational models offer a framework to investigate the influence of networks,
      as well as local tissue properties, and to explore alternative resection
      strategies. Here we study, using such a model, the influence of connections on
      seizures and how this might change our traditional views of epilepsy surgery. We
      use a simple network model consisting of four interconnected neuronal
      populations. One of these populations can be made hyperexcitable, modeling a
      pathological region of cortex. Using model simulations, the effect of surgery on
      the seizure rate is studied. We find that removal of the hyperexcitable
      population is, in most cases, not the best approach to reduce the seizure rate.
      Removal of normal populations located at a crucial spot in the network, the
      "driver," is typically more effective in reducing seizure rate. This work
      strengthens the idea that network structure and connections may be more important
      than localizing the pathological node. This can explain why lesionectomy may not
      always be sufficient.

PMID- 28744853
TI  - Poor Appetite and Dietary Intake in Community-Dwelling Older Adults.
AB  - BACKGROUND/OBJECTIVES: Poor appetite in older adults leads to sub-optimal food
      intake and increases the risk of undernutrition. The impact of poor appetite on
      food intake in older adults is unknown. The aim of this study was to examine the
      differences in food intake among older community-dwelling adults with different
      reported appetite levels. DESIGN: Cross-sectional analysis of data from a
      longitudinal prospective study. SETTING: Health, aging, and body composition
      study performed in the USA. PARTICIPANTS: 2,597 community-dwelling adults aged 70
      79. MEASUREMENTS: A semi-quantitative, interviewer-administered, 108-item food
      frequency questionnaire designed to estimate dietary intake. Poor appetite was
      defined as the report of a moderate, poor, or very poor appetite in the past
      month and was compared with good or very good appetite. RESULTS: The mean age of
      the study sample was 74.5 +/- 2.8 years; 48.2% were men, 37.7% were black, and
      21.8% reported a poor appetite. After adjustment for total energy intake and
      potential confounders (including biting/chewing problems), participants with a
      poor appetite had a significantly lower consumption of protein and dietary fiber,
      solid foods, protein rich foods, whole grains, fruits, and vegetables, but a
      higher consumption of dairy foods, fats, oils, sweets, and sodas compared to
      participants with very good appetite. In addition, they were less likely to
      report consumption of significant larger portion sizes. CONCLUSION: Older adults
      reporting a poor appetite showed a different dietary intake pattern compared to
      those with (very) good appetite. Better understanding of the specific dietary
      intake pattern related to a poor appetite in older adults can be used for
      nutrition interventions to enhance food intake, diet variety, and diet quality.

PMID- 28744854
TI  - BOK displays cell death-independent tumor suppressor activity in non-small-cell
      lung carcinoma.
AB  - As the genomic region containing the Bcl-2-related ovarian killer (BOK) locus is
      frequently deleted in certain human cancers, BOK is hypothesized to have a tumor
      suppressor function. In the present study, we analyzed primary non-small-cell
      lung carcinoma (NSCLC) tumors and matched lung tissues from 102 surgically
      treated patients. We show that BOK protein levels are significantly downregulated
      in NSCLC tumors as compared to lung tissues (p < 0.001). In particular, we found
      BOK downregulation in NSCLC tumors of grades two (p = 0.004, n = 35) and three (p
      = 0.031, n = 39) as well as in tumors with metastases to hilar (pN1) (p = 0.047,
      n = 31) and mediastinal/subcarinal lymph nodes (pN2) (p = 0.021, n = 18) as
      opposed to grade one tumors (p = 0.688, n = 7) and tumors without lymph node
      metastases (p = 0.112, n = 51). Importantly, in lymph node-positive patients, BOK
      expression greater than the median value was associated with longer survival (p =
      0.002, Mantel test). Using in vitro approaches, we provide evidence that BOK
      overexpression is inefficient in inducing apoptosis but that it inhibits TGFbeta
      induced migration and epithelial-to-mesenchymal transition (EMT) in lung
      adenocarcinoma-derived A549 cells. We have identified epigenetic mechanisms, in
      particular BOK promoter methylation, as an important means to silence BOK
      expression in NSCLC cells. Taken together, our data point toward a novel
      mechanism by which BOK acts as a tumor suppressor in NSCLC by inhibiting EMT.
      Consequently, the restoration of BOK levels in low-BOK-expressing tumors might
      favor the overall survival of NSCLC patients.

PMID- 28744855
TI  - Seizure outcome after hippocampal deep brain stimulation in patients with
      refractory temporal lobe epilepsy: A prospective, controlled, randomized, double
      blind study.
AB  - OBJECTIVE: We designed a prospective, randomized, controlled, double-blind study
      to evaluate the efficacy of hippocampal deep brain stimulation (Hip-DBS) in
      patients with refractory temporary lobe epilepsy (TLE). METHODS: Sixteen adult
      patients with refractory TLE were studied. Patient's workup included medical
      history, interictal and ictal electroencephalography (EEG), and high-resolution
      1.5T magnetic resonance imaging (MRI). Patients were randomized on a 1:1
      proportion to an active (stimulation on) or to a control (no stimulation) arm.
      After implantation, patients were allowed to recover for 1 month, which was
      followed by a 1-month titration (or sham) period. The 6-month blinded phase
      started immediately afterward. A postoperative MRI confirmed the electrode's
      position in all patients. All patients received bipolar continuous stimulation.
      Stimulus duration was 300 MUs and frequency was 130 Hz; final intensity was 2 V.
      Patients were considered responders when they had at least 50% seizure frequency
      reduction. RESULTS: All patients had focal impaired awareness seizures (FIAS,
      complex partial seizures), and 87% had focal aware seizures (FAS, simple partial
      seizures). Mean preoperative seizure frequency was 12.5 +/- 9.4 (mean +/-
      standard deviation) per month. MRI findings were normal in two patients,
      disclosed bilateral mesial temporal sclerosis (MTS) in three, left MTS in five,
      and right MTS in six patients. An insertional effect could be noted in both
      control and active patients. In the active group (n = 8), four patients became
      seizure-free; seven of eight were considered responders and one was a
      nonresponder. There was a significant difference regarding FIAS frequency between
      the two groups from the first month of full stimulation (p < 0.001) until the end
      of the blinded phase (p < 0.001). This was also true for FAS, except for the
      third month of the blinded phase. SIGNIFICANCE: Hip-DBS was effective in
      significantly reducing seizure frequency in patients with refractory TLE in the
      active group, as compared to the control group. Fifty-percent of the patients in
      the active group became seizure-free. The present study is the larger
      prospective, controlled, double-blind study to evaluate the effects of Hip-DBS
      published to date.

PMID- 28744857
TI  - The effect of pre-operative methylprednisolone on early endothelial damage after
      total knee arthroplasty: a randomised, double-blind, placebo-controlled trial.
AB  - We wished to evaluate whether inhibition of the systemic inflammatory response by
      a single pre-operative dose of methylprednisolone reduced markers of early
      endothelial damage after fast-track total knee arthroplasty. We randomly
      allocated 70 patients undergoing elective unilateral total knee arthroplasty
      (1:1) to receive either pre-operative intravenous methylprednisolone 125 mg
      (methylprednisolone group) or isotonic saline (control group). All procedures
      were performed under spinal anaesthesia without a tourniquet, using a
      standardised multimodal analgesic regime. The outcomes included changes in
      Syndecan-1 concentrations, a marker of glycocalyx degradation, markers of
      endothelial cell damage and activation (plasma soluble thrombomodulin and sE
      Selectin), and permeability by vascular endothelial growth factor, as well as C
      reactive protein concentrations. Blood samples were collected at baseline and 2
      h, 6 h and 24 h after surgery, with complete sampling from 63 patients for
      analyses. Methylprednisolone significantly reduced markers of endothelial damage
      at 24 h following surgery compared with saline (methylprednisolone group vs.
      control group, adjusted means (SEM)) expressed by circulating Syndecan-1: 11.6
      (1.0) ng.ml-1 vs. 13.4 (1.1) ng.ml-1 p = 0.046; soluble thrombomodulin: 5.1 (0.1)
      ng.ml-1 vs. 5.7 (0.2) ng.ml-1 , p = 0.009; sE-Selectin: 64.8 (1.8) ng.ml-1 vs.
      75.7 (1.9) ng.ml-1 , p = 0.001, and vascular endothelial growth factor: 35.3
      (2.7) ng.ml-1 vs. 58.5 (2.8) ng.ml-1 , p < 0.001. The effect of the intervention
      increased with time for soluble thrombomodulin, sE-Selectin and vascular
      endothelial growth factor, and was more pronounced in patients with high baseline
      values. Finally, methylprednisolone reduced the C-reactive protein response 24 h
      postoperatively; 31.1 (1.1) mg.l-1 vs. 68.4 (1.1) mg.l-1 , p < 0.001. Pre
      operative administration of methylprednisolone 125 mg reduced circulating markers
      of endothelial activation and damage, as well as the systemic inflammatory
      response (C-reactive protein) early after fast-track total knee arthroplasty.
      These findings may have a positive effect on surgical outcome, but require
      studies in major surgery.

PMID- 28744858
TI  - D-Malate decreases renal content of alpha-ketoglutarate, a driving force of
      organic anion transporters OAT1 and OAT3, resulting in inhibited tubular
      secretion of phenolsulfonphthalein, in rats.
AB  - d-Malate inhibits a Krebs cycle enzyme and the tubular transport of alpha
      ketoglutarate, an intermediate of the Krebs cycle and the driving force for rat
      organic anion transporter 1 (rOAT1) and rOAT3 in the kidney. This study examined
      the effects of d-malate on the rat organic anion transport system. The uptake of
      6-carboxyfluorescein by HEK293 cells expressing rOAT1 or rOAT3 was not affected
      by d-malate and l-malate. Up to 60 min after the intravenous injection of
      phenolsulfonphthalein (PSP), a typical substrate of the renal organic anion
      transporters, as a bolus to rats, 47.1% of the dose was recovered in the urine,
      and its renal clearance was estimated to be 8.60 ml/min/kg. d-Malate but not l
      malate interfered with its renal excretion, resulting in the delayed elimination
      of PSP from plasma. No effect of d-malate was recognized on creatinine clearance
      or the expression level of rOAT3 in the kidney cortex. d-Malate increased the
      plasma concentration of alpha-ketoglutarate. In addition, the compound greatly
      stimulated the renal excretion of alpha-ketoglutarate, implying that d-malate
      inhibited its reabsorption. The content of alpha-ketoglutarate was significantly
      decreased in the kidney cortex of rats administered d-malate. Collectively, this
      study shows that d-malate abrogates the tubular secretion of PSP, and the
      reduction of the renal content of alpha-ketoglutarate was proposed to be one of
      the mechanisms. A relationship between the reabsorption of alpha-ketoglutarate
      and the basolateral uptake of organic anion in the kidney is suggested.

PMID- 28744856
TI  - Age has a role in driving host immunopathological response to alphavirus
      infection.
AB  - Alphaviruses are a group of arthropod-borne pathogens capable of causing a wide
      spectrum of clinical symptoms, ranging from milder symptoms like rashes, fever
      and polyarthralgia, to life-threatening encephalitis. This genus of viruses is
      prevalent globally, and can infect patients across a wide age range.
      Interestingly, disease severity of virus-infected patients is wide-ranging.
      Definitions of the pathogenesis of alphaviruses, as well as the host factors
      influencing disease severity, remain limited. The innate and adaptive immune
      systems are important host defences against alphavirus infections. Several
      reports have highlighted the roles of specific immune subsets in contributing to
      the immune pathogenesis of these viruses. However, immunosenescence, a gradual
      deterioration of the immune system brought about by the natural advancement of
      age, affects the functional roles of these immune subsets. This phenomenon
      compromises the host's ability to defend against alphavirus infection and
      pathogenesis. In addition, the lack of maturity in the immune system in newborns
      and infants also results in more severe disease outcomes. In this review, we will
      summarize the subtle yet diverse physiological changes in the immune system
      during aging, and how these changes underlie the differences in disease severity
      for common alphaviruses.

PMID- 28744859
TI  - Lateral and axial cutting efficiency of instruments manufactured with
      conventional nickel-titanium and novel gold metallurgy.
AB  - AIM: To isolate the effect of metallurgy in lateral and axial cutting efficacy
      against plastic and bovine dentine substrates by comparing two rotary systems
      with identical design but manufactured with either conventional nickel-titanium
      or heat-treated gold alloy. METHODOLOGY: A total of 258 ProTaper Universal (PTU)
      and ProTaper Gold (PTG) Shaping instruments were used. Bending behaviour was
      assessed to determine the appropriate displacement associated with a 2 N force in
      lateral cutting. Ten instruments of each type were used in lateral action for 60
      s against bovine dentine or plastic substrates four consecutive times producing
      four notches in each specimen. Ten further instruments of each type were used in
      on axial action in four standardized simulated root canals fabricated from 4-mm
      thick plastic or dentine discs. Both tests were performed at 300 rpm in a
      computer-controlled testing platform. Notch area and torsional load were compared
      with Student's t-tests. Repeated measures ANOVA was used to compare cutting
      efficiency across the four different time-points. Pearson correlation
      coefficients between substrates were also determined. RESULTS: For lateral
      action, all three PTG instruments cut significantly more effectively (P < 0.05)
      than PTU on the plastic substrate. S1 and S2 PTG cut significantly more after 120
      and 180 s (P < 0.05) on bovine dentine substrate. For axial action, S1 and S2 PTG
      were significantly more efficient in cutting at 180 s on plastic and 120 s on
      bovine dentine (P < 0.05). CONCLUSION: Instruments made from heat-treated nickel
      titanium gold alloy had equal or greater cutting efficiency when compared to
      those made from conventional nickel-titanium.

PMID- 28744860
TI  - Echinocandins in antifungal pharmacotherapy.
AB  - OBJECTIVES: Echinocandins are the newest addition of the last decade to the
      antifungal armamentarium, which, owing to their unique mechanism of action,
      selectively target the fungal cells without affecting mammalian cells. Since the
      time of their introduction, they have come to occupy an important niche in the
      antifungal pharmacotherapy, due to their efficacy, safety, tolerability and
      favourable pharmacokinetic profiles. This review deals with the varying facets of
      echinocandins such as their chemistry, in-vitro and in-vivo evaluations, clinical
      utility and indications, pharmacokinetic and pharmacodynamic profiles, and
      pharmacoeconomic considerations. KEY FINDINGS: Clinical studies have demonstrated
      that the echinocandins - caspofungin, micafungin and anidulafungin - are
      equivalent, if not superior, to the mainstay antifungal therapies involving
      amphotericin B and fluconazole. Moreover, echinocandin regimen has been shown to
      be more cost-effective and economical. Hence, the echinocandins have found favour
      in the management of invasive systemic fungal infections. CONCLUSIONS: The subtle
      differences in echinocandins with respect to their pharmacology, clinical therapy
      and the mechanisms of resistance are emerging at a rapid pace from the current
      pool of research which could potentially aid in extending their utility in the
      fungal infections of the eye, heart and nervous system.

PMID- 28744861
TI  - Gonadal morphogenesis and sex differentiation in cultured Ussuri catfish
      Tachysurus ussuriensis.
AB  - The objective of this study was to investigate the optimal developmental time to
      perform sex reversal in Ussuri catfish Tachysurus ussuriensis, to develop monosex
      breeding in aquaculture. Systematic observations of gonadal sex differentiation
      of P. ussiriensis were conducted. The genital ridge formed at 9 days post
      fertilization (dpf) and germ cells begin to proliferate at 17 dpf. The ovarian
      cavity began forming on 21 dpf and completed by 25 dpf while presumptive testis
      remained quiescent. The primary oocytes were at the chromatin nucleolus stage by
      30 dpf, the peri-nucleolus stage by 44 dpf and the cortical alveoli stage by 64
      dpf. The germinal vesicle migrated towards the animal pole (polarization) at 120
      dpf. In presumptive testis, germ cells entered into mitosis and blood vessels
      appeared in the proximal gonad on 30 dpf. The efferent duct anlage appeared on 36
      dpf and formation of seminal lobules with spermatogonia and lobules interstitium
      occurred at 120 dpf. Therefore, gonadal sex differentiation occurred earlier in
      females than in males, with the histological differentiation preceding cytologic
      differentiation in T. ussuriensis. This indicates that undifferentiated gonads
      directly differentiate into ovary or testis between 17 and 21 dpf and artificial
      induction of sexual reversal by oral steroid administration must be conducted
      before 17 dpf.

PMID- 28744862
TI  - Mixed cryoglobulinaemia in a rhesus macaque (Macaca mulatta).
AB  - We report cryoglobulinaemia (CG) in a rhesus macaque whose serum sample was gel
      like at <37 degrees C and resolubilised upon warming. Mixed CG was diagnosed
      using serum protein electrophoresis and serum immunofixation electrophoresis.
      Renal damage and arthrophyma were observed during necropsy. This is the first
      report of CG in a non-human primate.

PMID- 28744863
TI  - Classification of changes occurring in lung patient during radiotherapy using
      relative gamma analysis and hidden Markov models.
AB  - PURPOSE: To present a new automated patient classification method based on
      relative gamma analysis and hidden Markov models (HMM) to identify patients
      undergoing important anatomical changes during radiation therapy. METHODS: Daily
      EPID images of every treatment field were acquired for 52 patients treated for
      lung cancer. In addition, CBCT were acquired on a regular basis. Gamma analysis
      was performed relative to the first fraction given that no significant anatomical
      change was observed on the CBCT of the first fraction compared to the planning
      CT. Several parameters were extracted from the gamma analysis (e.g., average
      gamma value, standard deviation, percent above 1). These parameters formed
      patient-specific time series. Data from the first 24 patients were used as a
      training set for the HMM. The trained HMM was then applied to the remaining 28
      patients and compared to manual clinical evaluation and fixed thresholds.
      RESULTS: A three-category system was used for patient classification ranging from
      minor deviations (category 1) to severe deviations (category 3) from the
      treatment plan. Patient classified using the HMM lead to the same result as the
      classification made by a human expert 83% of the time. The HMM overestimate the
      category 10% of the time and underestimate 7% of the time. Both methods never
      disagree by more than one category. In addition, the information provided by the
      HMM is richer than the simple threshold-based approach. HMM provides information
      on the likelihood that a patient will improve or deteriorate as well as the
      expected time the patient will remain in that state. CONCLUSION: We showed a
      method to classify patients during the course of radiotherapy based on relative
      changes in EPID images and a hidden Markov model. Information obtained through
      this automated classification can complement the clinical information collected
      during treatment and help identify patients in need of a plan adaptation.

PMID- 28744864
TI  - Impact of timing of recurrence following catheter ablation of scar-related
      ventricular tachycardia on subsequent mortality.
AB  - BACKGROUND: Catheter ablation (CA) has an established role in scar-related
      ventricular tachycardia (VT), but the risk of recurrences is substantial and the
      appropriate intensity of postablation monitoring unknown. The implication of
      timing of postablation VT recurrence has not been adequately investigated.
      METHODS: We studied 120 consecutive patients with scar-related VT (age 60 +/- 15
      years, left ventricular ejection fraction 39 +/- 16%, 52% ischemic etiology) with
      at least 2 years of follow-up. Timing of VT recurrence was classified as very
      early (<1 month), early (1-6 months), or late (>6 months). RESULTS: At 24 months
      follow-up, 53 (44%) patients had recurrent VT, with eight (15%) having very early
      recurrence, 17 (32%) early recurrence, and 28 (53%) late recurrence. Mortality
      rates at 2 years were significantly higher in patients with very early VT
      recurrence (38%) compared to those with early (12%), late (7%), and no (3%)
      recurrences (log-rank P < 0.001). Very early VT recurrence was associated with an
      increased risk of death (odds ratio = 5.68, 95% confidence interval = 1.06-30.62,
      P = 0.04), while recurrent VT beyond 6 months was not associated with increased
      risk of mortality (P = 0.94). CONCLUSIONS: Timing of VT recurrence following CA
      of scar-related VT impacts subsequent risk of mortality. Patients experiencing VT
      recurrence within 1-6 months from the procedure are at particularly high risk.
      These data support the importance of intense postablation monitoring for at least
      6 months after the procedure to identify patients with early VT recurrence who
      may benefit from additional therapeutic interventions to improve outcomes.

PMID- 28744865
TI  - A unique invertase is important for sugar absorption of an obligate biotrophic
      pathogen during infection.
AB  - An increased invertase activity in infected plant tissue has been observed in
      many plant-pathogen interactions. However, the origin of this increased invertase
      activity (plant and/or pathogen) is still under debate. In addition, the role of
      pathogen invertases in the infection process is also unclear. We identified and
      cloned a gene with homology to invertases from Puccinia striiformis f. sp.
      tritici (Pst). Transcript levels of PsINV were analyzed by quantitative reverse
      transcription PCR in both compatible and incompatible Pst-wheat interactions .
      Function of the gene product was confirmed by heterologous expression, and its
      function in Pst infection was analyzed by host-induced gene silencing (HIGS). Pst
      abundantly secretes invertase during its invasion attempts whether in a
      compatible or incompatible interaction with wheat. Further research into the
      different domains of this protein indicated that the rust-specific sequence
      contributes to a higher efficiency of sucrose hydrolysis. With PsINV silenced by
      HIGS during the infection process, growth of Pst is inhibited and conidial
      fructification incomplete. Finally, pathogenicity of Pst is impaired and spore
      yield significantly reduced. Our results clearly demonstrate that this Pst
      invertase plays a pivotal role in this plant-pathogen interaction probably by
      boosting sucrose hydrolysis to secure the pathogen's sugar absorption.

PMID- 28744866
TI  - Effect of moderate, 30 percent global maternal nutrient reduction on fetal and
      postnatal baboon phenotype.
AB  - BACKGROUND: Most developmental programming studies on maternal nutrient reduction
      (MNR) are in altricial rodents whose maternal nutritional burden and offspring
      developmental trajectory differ from precocial non-human primates and humans.
      METHODS: Control (CTR) baboon mothers ate ad libitum; MNR mothers ate 70% global
      control diet in pregnancy and lactation. RESULTS: We present offspring
      morphometry, blood cortisol, and adrenocorticotropin (ACTH) during second half of
      gestation (G) and first three postnatal years. Moderate MNR produced intrauterine
      growth restriction (IUGR). IUGR males (n=43) and females (n=28) were smaller than
      CTR males (n=50) and females (n=47) in many measurements at many ages. In CTR,
      fetal ACTH increased 228% and cortisol 48% between 0.65G and 0.9G. IUGR ACTH was
      elevated at 0.65G and cortisol at 0.9G. 0.9G maternal gestational weight gain,
      fetal weight, and placenta weight were correlated. CONCLUSIONS: Moderate IUGR
      decreased body weight and morphometric measurements at key time points and
      altered hypothalamo-pituitary-adrenal function.

PMID- 28744868
TI  - A new diminutive genus and species of catfish from Lake Tanganyika (Siluriformes:
      Clariidae).
AB  - The examination of material representing one of Lake Tanganyika's six previously
      recognized endemic catfish lineages, has revealed the presence of an additional
      genus of clariid, described here as Pseudotanganikallabes new genus. This genus
      is represented by a single species, Pseudotanganikallabes prognatha sp. nov.,
      which is distinguished from all other clariids by its lack of an infraorbital
      series, the presence of multiple osseous connections between the swim bladder
      capsules and elements of the neurocranium, the absence of an ethmoid notch, the
      presence of a very large, egg-shaped occipital fontanelle and the extension of
      the lower lip beyond the margin of the upper jaw. A combination of additional
      external and molecular characters serves to further distinguish this taxon from
      all currently recognized clariid species. Phylogenetic analysis of mitochondrial
      (cytb) and nuclear (18S-ITS1-5.8S-ITS2-28S) sequence data supports the creation
      of a new genus for this species, as it appears to represent an independent,
      monophyletic lineage within the family Clariidae.

PMID- 28744869
TI  - A meta-analysis on growth, physiological, and biochemical responses of woody
      species to ground-level ozone highlights the role of plant functional types.
AB  - The carbon-sink strength of temperate and boreal forests at midlatitudes of the
      northern hemisphere is decreased by ozone pollution, but knowledge on subtropical
      evergreen broadleaved forests is missing. Taking the dataset from Chinese studies
      covering temperate and subtropical regions, effects of elevated ozone
      concentration ([O3 ]) on growth, biomass, and functional leaf traits of different
      types of woody plants were quantitatively evaluated by meta-analysis. Elevated
      mean [O3 ] of 116 ppb reduced total biomass of woody plants by 14% compared with
      control (mean [O3 ] of 21 ppb). Temperate species from China were more sensitive
      to O3 than those from Europe and North America in terms of photosynthesis and
      transpiration. Significant reductions in chlorophyll content, chlorophyll
      fluorescence parameters, and ascorbate peroxidase induced significant injury to
      photosynthesis and growth (height and diameter). Importantly, subtropical species
      were significantly less sensitive to O3 than temperate ones, whereas deciduous
      broadleaf species were significantly more sensitive than evergreen broadleaf and
      needle-leaf species. These findings suggest that carbon-sink strength of Chinese
      forests is reduced by present and future [O3 ] relative to control (20-40 ppb).
      Given that (sub)-tropical evergreen broadleaved species dominate in Chinese
      forests, estimation of the global carbon-sink constraints due to [O3 ] should be
      re-evaluated.

PMID- 28744867
TI  - Antiepileptic drug discontinuation by people with epilepsy in the general
      population.
AB  - OBJECTIVE: Rate, reasons, and predictors of antiepileptic drug (AED)
      discontinuation were investigated in a well-defined cohort of people with
      epilepsy to verify efficacy and tolerability of treatment up to 20 years from
      treatment initiation. METHODS: The history of AED usage in children and adults
      with epilepsy registered with 123 family physicians in an area of Northern Italy
      between 2000 and 2008 was recorded. Cumulative probabilities of AED withdrawal
      for specific reasons were estimated using cumulative incidence functions. The
      probabilities of withdrawing for terminal remission, and of achieving sustained
      remission while still on treatment, were also evaluated. The roles of sex, age at
      diagnosis, seizure types, duration at diagnosis, and syndrome were assessed with
      hazard ratios and 95% confidence intervals. RESULTS: Seven hundred thirty-one of
      747 individuals were treated with one or more AEDs during the disease course. The
      three commonest drugs were valproate, carbamazepine, and phenobarbital. Reported
      reasons for AED withdrawal were, in decreasing order, terminal remission,
      ineffectiveness, and adverse events. The probability of withdrawing the first AED
      for terminal remission was 1.0% at 1 year and increased to 20.0% at 20 years.
      Corresponding rates were 2.9% and 12.6% for ineffectiveness and 0.5% and 3.3% for
      adverse events. Reasons for withdrawal varied with individuals' age, sex, disease
      characteristics, and drugs. SIGNIFICANCE: The initial AED given was retained in
      the majority of cases. Terminal remission, lack of efficacy, and adverse effects
      were, in decreasing order, the commonest reasons for AED discontinuation.
      Withdrawal could be predicted by age at diagnosis, sex, and clinical
      characteristics and varies among drugs.

PMID- 28744870
TI  - Fast dose optimization for rotating shield brachytherapy.
AB  - PURPOSE: To provide a fast computational method, based on the proximal graph
      solver (POGS) - A convex optimization solver using the alternating direction
      method of multipliers (ADMM), for calculating an optimal treatment plan in
      rotating shield brachytherapy (RSBT). RSBT treatment planning has more degrees of
      freedom than conventional high-dose-rate brachytherapy due to the addition of
      emission direction, and this necessitates a fast optimization technique to enable
      clinical usage. METHODS: The multi-helix RSBT (H-RSBT) delivery technique was
      investigated for five representative cervical cancer patients. Treatment plans
      were generated for all patients using the POGS method and the commercially
      available solver IBM ILOG CPLEX. The rectum, bladder, sigmoid colon, high-risk
      clinical target volume (HR-CTV), and HR-CTV boundary were the structures included
      in our optimization, which applied an asymmetric dose-volume optimization with
      smoothness control. Dose calculation resolution was 1 * 1 * 3 mm3 for all cases.
      The H-RSBT applicator had 6 helices, with 33.3 mm of translation along the
      applicator per helical rotation and 1.7 mm spacing between dwell positions,
      yielding 17.5 degrees  emission angle spacing per 5 mm along the applicator.
      RESULTS: For each patient, HR-CTV D90 , HR-CTV D100 , rectum D2cc , sigmoid D2cc
      , and bladder D2cc matched within 1% for CPLEX and POGS methods. Also, similar
      EQD2 values between CPLEX and POGS methods were obtained. POGS was around 18
      times faster than CPLEX. For all patients, total optimization times were 32.1
      65.4 s for CPLEX and 2.1-3.9 s for POGS. CONCLUSIONS: POGS reduced treatment plan
      optimization time approximately 18 times for RSBT with similar HR-CTV D90 , organ
      at risk (OAR) D2cc values, and EQD2 values compared to CPLEX, which is
      significant progress toward clinical translation of RSBT.

PMID- 28744871
TI  - Genotyping of Tenacibaculum maritimum isolates from farmed Atlantic salmon in
      Western Canada.
AB  - Mouthrot infections (bacterial stomatitis) have a significant impact on the
      Atlantic salmon aquaculture industry in Western Canada due to economic losses and
      fish welfare. Bacteria isolated from lesions in the field have been identified as
      Tenacibaculum maritimum. Mouthrot is different to classical tenacibaculosis,
      which is most commonly associated with ulcerative lesions, frayed fins and tail
      rot. The marine fish pathogen T. maritimum is found worldwide; however, in
      Western Canada, the knowledge of the genetic profile of T. maritimum is limited.
      This study looked at increasing this knowledge by genotyping T. maritimum
      isolates collected from Atlantic salmon from farms in Western Canada. These
      genotypes were compared to other species of the genus Tenacibaculum, as well as
      other known sequence types within the species. The Western Canadian isolates
      belong to two new sequence types within the T. maritimum species. Phylogenetic
      analysis shows that the isolates form a distinct branch together with T.
      maritimum NCIMB 2154T separate from other Tenacibaculum type strains, and they
      are most closely related to strains from Norway and Chile.

PMID- 28744872
TI  - Antibiotic prescription for endodontic infections: a survey of Brazilian
      Endodontists.
AB  - AIM: To investigate antibiotic prescribing habits reported by Brazilian
      endodontists in specific clinical situations. METHODOLOGY: Brazilian endodontists
      (n = 13 853) were invited to answer an online questionnaire. The questionnaire
      consisted of two parts: the first part contained personal data such as age,
      gender, years of experience and location of endodontic practice; the second part
      included questions regarding their behaviour when prescribing antibiotics in
      dental practice. The subjects provided their registration number in the Regional
      Council of Dentistry (RCD) to prevent duplication of data. Data were collected
      and analysed by SPSS 17.0 (SPSS, Inc., Chicago, IL, USA). Chi-square and Fisher's
      exact tests were used to test the significance of possible associations (P <
      0.05). RESULTS: From the 13 853 questionnaires, a total of 615 were answered
      (4.44%). The first-choice antibiotic was amoxicillin (81.5%), followed by
      amoxicillin + clavulanic acid (30.7%). For acute apical abscesses with intra- and
      extraoral diffuse swelling, fever and trismus, 90.1% reported they would
      prescribe antibiotics, whilst 88.1% reported they would prescribe antibiotics
      even without extraoral swelling, fever and trismus, and 20.5% would prescribe
      antibiotics in cases of chronic apical periodontitis, and sinus tract. The first
      choice antibiotics varied by age of dentist (P < 0.001) and time elapsed since
      their endodontic graduation (P = 0.001). CONCLUSIONS: Many endodontists reported
      prescribing antibiotics in situations where they would not be indicated.
      Likewise, the general administration of antibiotics was longer in duration than
      necessary, reinforcing the need of continuous education regarding the use of
      antibiotics.

PMID- 28744873
TI  - Epicardial ablation of tachyarrhythmia in children: Experience at two academic
      centers.
AB  - BACKGROUND: Experience with percutaneous epicardial ablation of tachyarrhythmia
      in pediatrics is limited. This case series addresses the feasibility, safety, and
      complications of the procedure in children. METHODS: A total of nine patients
      underwent 10 epicardial ablation procedures from 2002 to 2013 at two academic
      centers. Activation mapping was performed in all cases, and electroanatomic map
      was utilized in nine of the 10 procedures. Patients had undergone one to three
      failed endocardial catheter ablations in addition to medical management, and all
      had symptoms, a high-risk accessory pathway (AP), aborted cardiac arrest with
      Wolff-Parkinson-White syndrome (WPW), or ventricular dysfunction. A standard
      epicardial approach was used for access in all cases, using a 7- or 8- Fr sheath.
      Epicardial ablation modality was radiofrequency (RF) in seven, cryoablation
      (CRYO) in one, and CRYO plus RF in one. RESULTS: Median age was 14 (range 8-19)
      years. INDICATIONS: drug refractory ectopic atrial tachycardia (one), ventricular
      tachycardia (VT) (five), high-risk AP (two), and aborted cardiac arrest from WPW 
      (one). Epicardial ablation was not performed in one case despite access due to
      an inability to maneuver the catheter around a former pericardial scar. VT foci
      included the right ventricular outflow tract septum, high posterior left
      ventricle (LV), LV outflow tract, postero-basal LV, and scar from previous
      rhabdomyoma surgery. WPW foci were in the area of the posterior septum and
      coronary sinus in all three cases. Overall procedural success was 70% (7/10),
      with epicardial ablation success in five and endocardial ablation success after
      epicardial mapping in two. The VT focus was close to the left anterior descending
      coronary artery in one of the unsuccessful cases in which both RF and CRYO were
      used. There was one recurrence after a successful epicardial VT ablation, which
      was managed with a second successful epicardial procedure. There were no other
      recurrences at more than 1 year of follow-up. Complications were minimal, with
      one case of inadvertent pleural access requiring no specific therapy. No
      pericarditis or effusion was seen in any of the patients who underwent epicardial
      ablation. CONCLUSION: Epicardial ablation in pediatric patients can be performed
      with low complications and acceptable success. It can be considered for a
      spectrum of tachycardia mechanisms after failed endocardial ablation attempts and
      suspected epicardial foci. Success and recurrence may be related to foci in
      proximity to the epicardial coronaries, pericardial scar, or a distant location
      from the closest epicardial location. Repeat procedures may be necessary.

PMID- 28744874
TI  - Protracted volitional spawning of pinfish Lagodon rhomboides and changes in egg
      quality and fatty-acid composition throughout the spawning season.
AB  - Spawning performance of pinfish Lagodon rhomboides without use of hormonal aids
      was monitored over an extended season. Nearly three million eggs were obtained
      from 75 spawns collected over a 90-day consecutive period from a single
      population of four brood fish (1M:1F). A mean +/- s.d. batch fecundity of 30.27
      +/- 22.64 eggs g-1 female was estimated with 98.0 +/- 0.06% of the batch composed
      of floating eggs which were 1.04 +/- 0.04 mm in diameter and 85.71 +/- 27.59%
      fertile. Floating eggs successfully hatched 54.65 +/- 29.13% of the time which
      yielded larvae that were 2.59 +/- 0.24 mm in length. Fatty acids within floating
      eggs were largely represented by polyunsaturated fatty acids (45.30 +/- 2.14% of
      total fatty acids) of which linoleic acid [(c18:2n-6cis) 3.49 +/- 1.69%
      trifluoroacetic acid (TFA)] and docosahexaenoic acid (DHA) [(c22:6n-3) 28.47 +/-
      1.48% TFA] represented the majority of fatty acids for n-6 and n-3
      polyunsaturated fatty acids, respectively. The strongest correlations between
      fatty acids and hatching success and larval survival to first feeding were
      observed for the DHA:EPA (eicosapentaenoic acid; c20:5n-3) ratio and total n-6
      polyunsaturated fatty-acids levels, respectively. These data demonstrate
      potential for producers to rely on natural spawns for extensive egg production
      and provide a baseline for future development of natural spawning protocols of
      captive L. rhomboides.

PMID- 28744875
TI  - Semiparametric Bayesian analysis of accelerated failure time models with cluster
      structures.
AB  - In this paper, we develop a Bayesian semiparametric accelerated failure time
      model for survival data with cluster structures. Our model allows distributional
      heterogeneity across clusters and accommodates their relationships through a
      density ratio approach. Moreover, a nonparametric mixture of Dirichlet processes
      prior is placed on the baseline distribution to yield full distributional
      flexibility. We illustrate through simulations that our model can greatly improve
      estimation accuracy by effectively pooling information from multiple clusters,
      while taking into account the heterogeneity in their random error distributions.
      We also demonstrate the implementation of our method using analysis of Mayo
      Clinic Trial in Primary Biliary Cirrhosis.

PMID- 28744876
TI  - A semiparametric method for comparing the discriminatory ability of biomarkers
      subject to limit of detection.
AB  - Receiver operating characteristic curves and the area under the curves (AUC) are
      often used to compare the discriminatory ability of potentially correlated
      biomarkers. Many biomarkers are subject to limit of detection due to the
      instrumental limitation in measurements and may not be normally distributed.
      Standard parametric methods assuming normality can lead to biased results when
      the normality assumption is violated. We propose new estimation and inference
      procedures for the AUCs of biomarkers subject to limit of detection by using the
      semiparametric transformation model allowing for heteroscedasticity. We obtain
      the nonparametric maximum likelihood estimators by maximizing the likelihood for
      the observed data with limit of detection. The proposed estimators are shown to
      be consistent, asymptotically normal, and asymptotically efficient. Additionally,
      we propose a Wald type test statistic to compare the AUCs of 2 potentially
      correlated biomarkers with limit of detection. Extensive simulation studies
      demonstrate that the proposed method is robust to nonnormality while performing
      as well as its parametric counterpart when the normality assumption is true. An
      application to an autism study is provided.

PMID- 28744877
TI  - Empirical likelihood-based confidence intervals for mean medical cost with
      censored data.
AB  - In this paper, we propose empirical likelihood methods based on influence
      function and jackknife techniques for constructing confidence intervals for mean
      medical cost with censored data. We conduct a simulation study to compare the
      coverage probabilities and interval lengths of our proposed confidence intervals
      with that of the existing normal approximation-based confidence intervals and
      bootstrap confidence intervals. The proposed methods have better finite-sample
      performances than existing methods. Finally, we illustrate our proposed methods
      with a relevant example.

PMID- 28744878
TI  - Explaining sex differences in lifespan in terms of optimal energy allocation in
      the baboon.
AB  - We provide a quantitative test of the hypothesis that sex role specialization may
      account for sex differences in lifespan in baboons if such specialization causes
      the dependency of fitness upon longevity, and consequently the optimal resolution
      to an energetic trade-off between somatic maintenance and other physiological
      functions, to differ between males and females. We present a model in which
      females provide all offspring care and males compete for access to reproductive
      females and in which the partitioning of available energy between the competing
      fitness-enhancing functions of growth, maintenance, and reproduction is modeled
      as a dynamic behavioral game, with the optimal decision for each individual
      depending upon his/her state and the behavior of other members of the population.
      Our model replicates the sexual dimorphism in body size and sex differences in
      longevity and reproductive scheduling seen in natural populations of baboons. We
      show that this outcome is generally robust to perturbations in model parameters,
      an important finding given that the same behavior is seen across multiple
      populations and species in the wild. This supports the idea that sex differences
      in longevity result from differences in the value of somatic maintenance relative
      to other fitness-enhancing functions in keeping with the disposable soma theory.

PMID- 28744879
TI  - Procarbazine, lomustine and vincristine for recurrent high-grade glioma.
AB  - BACKGROUND: Recurrent high-grade glioma (HGG) carries an extremely poor
      prognosis. There is no current standard of care or guideline-based
      recommendations. Nitrosourea-based multidrug chemotherapy or PCV - procarbazine,
      lomustine (CCNU) and vincristine - is one of the treatment options at recurrence.
      There has been no meta-analysis which looks at the benefits and harms of PCV
      chemotherapy in adults with recurrent HGG. OBJECTIVES: To assess the
      effectiveness and safety of procarbazine, lomustine, and vincristine (PCV)
      chemotherapy with other interventions in adults with recurrent high-grade glioma.
      To investigate whether predefined subgroups of people benefit more or less from
      chemotherapy. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL Issue 4, 2017), MEDLINE (1946 to 22 May 2017), and
      Embase (1980 to 22 May 2017). We searched trial registries including the World
      Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP;
      apps.who.int/trialsearch) and the National Institutes of Health (NIH;
      ClinicalTrials.gov). We searched the reference lists of all identified studies;
      the electronic table of contents of the Journal of Neuro-Oncology (1983 to 2016)
      and Neuro-Oncology (1999 to 2016); and conference abstracts from the Society for
      Neuro-Oncology (SNO) and the American Society of Clinical Oncology (ASCO 2004 to
      2016). We also searched unpublished grey literature and other regional databases.
      There were no language restrictions. SELECTION CRITERIA: Randomised controlled
      trials (RCTs), quasi-randomised trials (QRCTs), or controlled clinical trials
      (CCTs) where PCV was used to treat adults with recurrent HGG. Comparison arm
      included no chemotherapy, other second line chemotherapy or best supportive care.
      DATA COLLECTION AND ANALYSIS: Two review authors extracted the data and undertook
      a 'Risk of bias' assessment and critical appraisal of the studies. MAIN RESULTS:
      We identified two RCTs meeting our inclusion criteria. The two trials tested
      different comparisons.One RCT included 35 participants and compared PCV with
      'eight drugs in one day' multidrug chemotherapy, which is a combination of drugs
      with different mechanisms of action. Median survival was 6 months for the PCV
      group and 6.5 months for the 'eight drugs in one day' group. Adverse event
      outcomes were not graded or quantified. Progression-free survival (PFS) and
      quality of life (QoL) were not described in the methods and were not an outcome
      of interest. The sample size in this study was small, which lead to insufficient
      statistical power to detect clinical differences. According to the GRADE approach
      we judged the quality of evidence to be low for survival outcome and very low for
      chemotherapy toxicityThe second multi-institutional RCT included 447 participants
      and compared PCV with Temozolomide (TMZ). Participants were randomised into three
      arms to receive PCV, and two different regimens of TMZ in a 2:1:1 ratio at first
      recurrence. The trial reported a median overall survival of 6.7 months and 7.2
      months for the PCV and TMZ group respectively. It reported a PFS of 3.6 months
      for the PCV group and 4.7 months for the TMZ group. There was no observed
      difference of effect on overall survival (hazard ratio (HR) 0.91, 95% CI 0.74 to
      1.11; P = 0.35) or PFS (HR 0.89, 95% CI 0.73 to 1.08; P = 0.23) in participants
      receiving PCV or TMZ chemotherapy. The proportion of people with at least one
      grade 3 or 4 adverse event was not clinically important at 9.2% versus 12.2% in
      PCV and TMZ arms respectively. Mean QoL scores calculated at baseline, 12 weeks
      and 24 weeks was 51.9 versus 59.8 favouring TMZ (P = 0.04) which is statistically
      but not clinically significant and was less than the pre-defined 10 point change
      for moderate improvement. We judged the GRADE quality of evidence to be moderate
      for overall survival, PFS, and chemotherapy toxicity and low for QoL. AUTHORS'
      CONCLUSIONS: Evidence is based on a single large trial analysis as the other
      trial was small, with inadequate power to detect survival difference.
      Chemotherapy-naive patients with HGG at first recurrence when treated with PCV or
      TMZ have similar survival and time-to-progression outcomes. Adverse events are
      similar and QoL scores are statistically but not clinically significant between
      TMZ and PCV. Further RCTs should be conducted with adequate power following
      CONSORT guidelines with emphasis on QoL outcomes.

PMID- 28744880
TI  - Chemical composition and diuretic, natriuretic and kaliuretic effects of extracts
      of Mimosa bimucronata (DC.) Kuntze leaves and its majority constituent methyl
      gallate in rats.
AB  - OBJECTIVES: Some species of the genus Mimosa showed promising results in previous
      investigations, which include diuretic effect; however, no chemical analyses or
      animal model has been conducted so far to evaluate the biological properties of
      M. bimucronata. METHODS: Male Wistar rats received the oral treatment with
      vehicle; hydrochlorothiazide; methanolic extract from M. bimucronata (MEMB),
      dichloromethane (DCM) and ethyl acetate (EA) fractions or methyl gallate (MG).
      The cumulative urine volume, electrolytes excretion, pH and osmolality were
      determined at the end of the experiment. KEY FINDINGS: The chemical studies
      demonstrated that the phenolic compounds are the majorities in the plant, with
      the MG being the main substance identified. We showed that MEMB and EA fraction,
      but not DCM, exhibited diuretic and saluretic effects. Similarly, the MG also
      revealed diuretic, natriuretic and kaliuretic properties to both normotensive and
      spontaneously hypertensive rats. Atropine, a muscarinic receptor antagonist,
      fully prevented MG-induced diuresis and saluresis. In addition, MG did not alter
      the viability of A7r5 and L929 cell lines and neither stimulated nitric oxide
      generation. CONCLUSIONS: These findings suggest that M. bimucronata extracts and
      its majority compound MG present diuretic, natriuretic and kaliuretic properties,
      which was dependent on the activation of muscarinic acetylcholine receptor.

PMID- 28744881
TI  - New common program requirements for the resident physician workforce and the
      omission of strategic napping: A missed opportunity.
AB  - OBJECTIVES: Napping has known benefits for fatigue mitigation and improved
      alertness. However the Accreditation Council for Graduate Medical Education
      (ACGME) New Common Program Requirements recently removed the 16 h work limit for
      PGY1 residents and removed any suggestions of napping. METHODS: We utilized a
      cross-sectional study design to administer a 44-item questionnaire in June 2016
      to 858 residents and fellows at one large urban academic medical center. We
      assessed: 1) resident physician sentiment of work environment supportiveness for
      napping at work; and 2) agreement with 2011 ACGME guidelines on workweek hour
      limitations and strategic napping recommendations. RESULTS: While 89% of
      residents reported access to an on-call room at work, only 20% felt their work
      environment supported a culture of napping while at work. Over 76% expressed
      agreement with the 2011 ACGME work-hour restrictions. CONCLUSIONS: Strategies to
      support napping and well-being within the resident physician workforce and
      organizational setting are warranted.

PMID- 28744882
TI  - Epstein-Barr virus positivity is associated with angiogenesis in, and poorer
      survival of, patients receiving standard treatment for classical Hodgkin's
      lymphoma.
AB  - Epstein-Barr virus (EBV) is a significant contributor to the development of
      classical Hodgkin's lymphoma (cHL). Recent studies have documented associations
      between angiogenesis and EBV-associated malignancies. No study has yet examined
      the associations among, and prognostic implications of, EBV infection, vascular
      endothelial growth factor (VEGF) expression, and microvessel density (MVD) in cHL
      patients. Diagnostic tissues from 135 cHL patients treated with adriamycin,
      bleomycin, vinblastine, and dacarbazine (ABVD) were retrospectively evaluated by
      in situ hybridization of EBV-encoded small RNA (EBER) and immunohistochemical
      staining for VEGF and CD31 (a measure of MVD). EBER and VEGF expression were
      positively correlated (P = 0.038). The mean MVD value of EBER-positive tumors was
      significantly higher than that of EBER-negative tumors (P = 0.034). The mean MVD
      of tumors positive for both EBER and VEGF was significantly higher than that of
      tumors negative for both markers (P = 0.008). EBER-positive patients had a lower
      5-year overall survival (OS) rate than EBER-negative patients (P = 0.046). A high
      MVD was also associated with a poorer OS (P = 0.01); multivariate analysis showed
      that this was a significant and independent prognostic factor (P = 0.026). We
      found positive correlations between EBER and VEGF levels, and the MVD, indicating
      that EBV plays an important role in tumor angiogenesis. Targeting of both
      angiogenesis and EBV may be important when treating cHL patients who are EBER
      positive and/or have a high MVD.

PMID- 28744883
TI  - Doubly robust inference for targeted minimum loss-based estimation in randomized
      trials with missing outcome data.
AB  - Missing outcome data is a crucial threat to the validity of treatment effect
      estimates from randomized trials. The outcome distributions of participants with
      missing and observed data are often different, which increases bias. Causal
      inference methods may aid in reducing the bias and improving efficiency by
      incorporating baseline variables into the analysis. In particular, doubly robust
      estimators incorporate 2 nuisance parameters: the outcome regression and the
      missingness mechanism (ie, the probability of missingness conditional on
      treatment assignment and baseline variables), to adjust for differences in the
      observed and unobserved groups that can be explained by observed covariates. To
      consistently estimate the treatment effect, one of these nuisance parameters must
      be consistently estimated. Traditionally, nuisance parameters are estimated using
      parametric models, which often precludes consistency, particularly in moderate to
      high dimensions. Recent research on missing data has focused on data-adaptive
      estimation to help achieve consistency, but the large sample properties of such
      methods are poorly understood. In this article, we discuss a doubly robust
      estimator that is consistent and asymptotically normal under data-adaptive
      estimation of the nuisance parameters. We provide a formula for an asymptotically
      exact confidence interval under minimal assumptions. We show that our proposed
      estimator has smaller finite-sample bias compared to standard doubly robust
      estimators. We present a simulation study demonstrating the enhanced performance
      of our estimators in terms of bias, efficiency, and coverage of the confidence
      intervals. We present the results of an illustrative example: a randomized,
      double-blind phase 2/3 trial of antiretroviral therapy in HIV-infected persons.

PMID- 28744884
TI  - Shear Stress-Induced Total Blood Trauma in Multiple Species.
AB  - The common complications in heart failure patients with implanted ventricular
      assist devices (VADs) include hemolysis, thrombosis, and bleeding. These are
      linked to shear stress-induced trauma to erythrocytes, platelets, and von
      Willebrand factor (vWF). Novel device designs are being developed to reduce the
      blood trauma, which will need to undergo in vitro and in vivo preclinical testing
      in large animal models such as cattle, sheep, and pig. To fully understand the
      impact of device design and enable translation of preclinical results, it is
      important to identify any potential species-specific differences in the VAD
      associated common complications. Therefore, the purpose of this study was to
      evaluate the effects of shear stress on cells and proteins in bovine, ovine, and
      porcine blood compared to human. Blood from different species was subjected to
      various shear rates (0-8000/s) using a rheometer. It was then analyzed for
      complete blood counts, hemolysis by the Harboe assay, platelet activation by flow
      cytometry, vWF structure by immunoblotting, and function by collagen binding
      activity ELISA (vWF : CBA). Overall, increasing shear rate caused increased total
      blood trauma in all tested species. This analysis revealed species-specific
      differences in shear-induced hemolysis, platelet activation, and vWF structure
      and function. Compared to human blood, porcine blood was the most resilient and
      showed less hemolysis, similar blood counts, but less platelet activation and
      less vWF damage in response to shear. Compared to human blood, sheared bovine
      blood showed less hemolysis, similar blood cell counts, greater platelet
      activation, and similar degradation of vWF structure, but less impact on its
      activity in response to shear. The shear-induced effect on ovine blood depended
      on whether the blood was collected via gravity at the abattoir or by venepuncture
      from live sheep. Overall, ovine abattoir blood was the least resilient in
      response to shear and bovine blood was the most similar to human blood. These
      results lay the foundations for developing blood trauma evaluation standards to
      enable the extrapolation of in vitro and in vivo animal data to predict safety
      and biocompatibility of blood-handling medical devices in humans. We advise using
      ovine venepuncture blood instead of ovine abattoir blood due to the greater
      overall damage in the latter. We propose using bovine blood for total blood
      damage in vitro device evaluation but multiple species could be used to create a
      full understanding of the complication risk profile of new devices. Further, this
      study highlights that choice of antibody clone for evaluating platelet activation
      in bovine blood can influence the interpretation of results from different
      studies.

PMID- 28744885
TI  - Water Infused Surface Protection as an Active Mechanism for Fibrin Sheath
      Prevention in Central Venous Catheters.
AB  - Protein adhesion in central venous catheters (CVCs) leads to fibrin sheath
      formation, the precursor to thrombotic and biofilm-related CVC failures. Advances
      in material properties and surface coatings do not completely prevent fibrin
      sheath formation and post-formation treatment options are limited and expensive.
      We propose water infused surface protection (WISP), an active method for
      prevention of fibrin sheath formation on CVCs, which creates a blood-free
      boundary layer on the inner surface of the CVC, limiting blood contact with the
      CVC lumen wall. A hollow fiber membrane (HFM) in a benchtop device served as a
      CVC testing model to demonstrate the WISP concept. Porcine blood was pumped
      through the HFM while phosphate buffered saline (PBS) was infused through the HFM
      wall, creating the WISP boundary layer. Protein adherences on model CVC surfaces
      were measured and imaged. Analytical and finite volume lubrication models were
      used to justify the assumption of a blood-free boundary layer. We found a 92.2%
      reduction in average adherent protein density when WISP is used, compared with
      our model CVC without WISP flow. Lubrication models matched our experimental
      pressure drop measurements suggesting that a blood-free boundary layer was
      created. The WISP technique also provides a novel strategy for drug
      administration for biofilm treatment. Reduction in adherent protein indicates a
      restriction on long-term fibrin sheath and biofilm formation making WISP a
      promising technology which improves a wide range of vascular access treatments.

PMID- 28744886
TI  - Development and validation of an LC-MS/MS method for the simultaneous
      quantification of seven constituents in rat plasma and application in a
      pharmacokinetic study of the Zaoren Anshen prescription.
AB  - A sensitive, specific and accurate liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method was developed and validated for the simultaneous determination
      of seven constituents of the Zaoren Anshen prescription (ZAP) in rat plasma after
      oral administration of the ZAP: spinosin, salvianic acid A, 6'''
      feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and
      deoxyschisandrin. The plasma samples and the internal standard (IS)
      sulfamethoxazole were extracted using acetonitrile. Chromatographic separation
      was performed with an Agilent HC-C18 column using a gradient elution profile and
      a mobile phase consisting of 0.01% formic acid in water (A) and acetonitrile (B).
      The analytes were quantified simultaneously in a single run using an ion trap
      mass spectrometer operated in the multiple reaction monitoring mode and
      electrospray ion-source polarity in the positive and negative modes. The
      calibration curves for spinosin, salvianic acid A, 6'''-feruloylspinosin,
      protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin were
      linear over the concentration ranges of 2.90-1160, 2.50-1000, 1.80-720, 0.65-260,
      2.50-1000, 8.00-1600 and 1.30-520 ng/mL, respectively. The intra- and inter-day
      precisions in terms of relative standard deviation were <18.9%, and the
      accuracies in terms of relative error were within +/-14.2%. Consequently, the
      proposed method was successfully applied to the pharmacokinetic analysis of these
      seven major active compounds in rats administered ZAP. These results will
      facilitate research aiming to predict the effectiveness of the optimal dose of
      ZAP and might be beneficial for the therapeutic use of ZAP in the clinical
      setting.

PMID- 28744887
TI  - In vitro evaluation of the internalization and toxicological profile of silica
      nanoparticles and submicroparticles for the design of dermal drug delivery
      strategies.
AB  - The use of colloidal silica nanoparticles and sub-microparticles (SiPs) have been
      considered a very interesting strategy for drug delivery applications. In the
      present study, we have focused our attention on the suitability of these
      nanomaterials as potential carriers for dermal drug delivery, thus studying their
      toxicological profile in vitro, cellular uptake and intracellular localization in
      both human keratinocytes (K17) and human dermal fibroblasts (HDF) as a function
      of their particle size (SiPs of 20, 70, 200 and 500 nm). Full characterization of
      these aspects enabled us to observe a strong cell-type dependency in terms of
      cytotoxicity and cell internalization, whereas particle size was only relevant
      for ultra-small SiPs (20 nm), being the most toxic SiPs. For 70, 200 and 500 nm
      SiPs, the differences in uptake and intracellular trafficking determined the
      different toxicological profiles in K17 and HDF. In addition, these
      characteristics can further define different drug delivery strategies. Hence,
      phagocytosis has been identified as the main internalization mechanism for K17,
      and caveolae-mediated endocytosis for HDF. This relevant information led us to
      conclude that fibroblasts would be optimal targets for delivering delicate
      therapeutic molecules such as proteins or genetic material using SiPs while
      maintaining a low toxicity profile, whereas keratinocytes could enable
      accelerated drug release therapies based on SiPs.

PMID- 28744888
TI  - Meta-analysis of gene-environment interaction exploiting gene-environment
      independence across multiple case-control studies.
AB  - Multiple papers have studied the use of gene-environment (G-E) independence to
      enhance power for testing gene-environment interaction in case-control studies.
      However, studies that evaluate the role of G-E independence in a meta-analysis
      framework are limited. In this paper, we extend the single-study empirical Bayes
      type shrinkage estimators proposed by Mukherjee and Chatterjee (2008) to a meta
      analysis setting that adjusts for uncertainty regarding the assumption of G-E
      independence across studies. We use the retrospective likelihood framework to
      derive an adaptive combination of estimators obtained under the constrained model
      (assuming G-E independence) and unconstrained model (without assumptions of G-E
      independence) with weights determined by measures of G-E association derived from
      multiple studies. Our simulation studies indicate that this newly proposed
      estimator has improved average performance across different simulation scenarios
      than the standard alternative of using inverse variance (covariance) weighted
      estimators that combines study-specific constrained, unconstrained, or empirical
      Bayes estimators. The results are illustrated by meta-analyzing 6 different
      studies of type 2 diabetes investigating interactions between genetic markers on
      the obesity related FTO gene and environmental factors body mass index and age.

PMID- 28744889
TI  - Health beliefs regarding pediatric cerebral palsy among caregivers in Botswana: A
      qualitative study.
AB  - BACKGROUND: Cerebral palsy (CP) is the most common motor disability worldwide
      with an incidence of 2.5 per 1,000 births globally. Health beliefs among
      caregivers may be major drivers of health-related behaviours and service
      utilization, but little is known regarding health beliefs around CP in Africa.
      METHODS: Between July 2013 and September 2015, children with CP were identified
      in Gaborone, Botswana, and their caregivers were invited to participate in a
      qualitative study utilizing semistructured in-person one-on-one interviews.
      Interview questions addressed their understanding of CP, challenges of caring for
      a handicapped child, and community response to children with CP. RESULTS: Sixty
      two caregivers participated in the study. Common themes elicited were variable
      knowledge about CP, financial and physical burden, lack of therapies and
      educational resources, and the impact of stigma. Caregivers in Botswana generally
      subscribed to a biomedical explanation of CP but expressed concerns regarding
      more stigmatizing folks beliefs expressed in the community. CONCLUSION: Health
      beliefs regarding CP in Botswana likely have a significant impact on utilization
      of healthcare resources. Information from this study should inform future
      educational interventions for caregivers of children with CP.

PMID- 28744890
TI  - Quantitative determination of trigonelline in mouse serum by means of hydrophilic
      interaction liquid chromatography-MS/MS analysis: Application to a
      pharmacokinetic study.
AB  - Trigonelline is a pyridine alkaloid found in fenugreek seeds and coffee beans.
      Most of the previous studies are concerned with the quantification of
      trigonelline along with other constituents in coffee herbs or beverages. Only a
      few have focused on its determination in animal or human tissues by applying
      different modes of HPLC with UV or MS detection. The aim of the study was to
      develop and validate a fast and simple method for trigonelline determination in
      serum by the use of hydrophilic interaction liquid chromatography (HILIC) with
      ESI-MS/MS detection. Separation of trigonelline was achieved on a Kinetex HILIC
      column operated at 35 degrees C with acetonitrile-ammonium formate (10 mm, pH =
      3) buffer mixture (55:45, v/v) as the mobile phase. The developed method was
      successfully applied to determine trigonelline concentration in mouse serum after
      intravenous administration of 10 mg/kg. The developed assay is sensitive (limit
      of detection = 1.5 ng/mL, limit of quantification = 5.0 ng/mL) and linear in a
      concentration range from 5.0 to 250.0 ng/mL. Sample preparation is limited to
      deproteinization, centrifugation and filtration. The application of the HILIC
      mode of chromatography with MS detection and selection of deuterated trigonelline
      as internal standard allowed a rapid and precise method of trigonelline
      quantification to be to developed.

PMID- 28744891
TI  - Qualitative research using realist evaluation to explain preparedness for
      doctors' memorable 'firsts'.
AB  - CONTEXT: Doctors must be competent from their first day of practice if patients
      are to be safe. Medical students and new doctors are acutely aware of this, but
      describe being variably prepared. OBJECTIVES: This study aimed to identify causal
      chains of the contextual factors and mechanisms that lead to a trainee being
      capable (or not) of completing tasks for the first time. METHODS: We studied
      three stages of transition: anticipation; lived experience, and post hoc
      reflection. In the anticipation stage, medical students kept logbooks and audio
      diaries and were interviewed. Consenting participants were followed into their
      first jobs as doctors, during which they made audio diaries to capture the lived
      experiences of transition. Reflection was captured using interviews and focus
      groups with other postgraduate trainee doctors. All materials were transcribed
      and references to first experiences ('firsts') were analysed through the lens of
      realist evaluation. RESULTS: A total of 32 medical students participated. Eleven
      participants were followed through the transition to the role of doctor. In
      addition, 70 postgraduate trainee doctors from three local hospitals who were
      graduates of 17 UK medical schools participated in 10 focus groups. We identified
      three categories of firsts (outcomes): firsts that were anticipated and
      deliberately prepared for in medical school; firsts for which total prior
      preparedness is not possible as a result of the step change in responsibility
      between the student and doctor identities, and firsts that represented
      experiences of failure. Helpful interventions in preparation (context) were
      opportunities for rehearsal and being given responsibility as a student in the
      clinical team. Building self-efficacy for tasks was an important mechanism.
      During transition, the key contextual factor was the provision of appropriate
      support from colleagues. CONCLUSIONS: Transition is a step change in
      responsibility for which total preparedness is not achievable. This transition is
      experienced as a rite of passage when the newly qualified doctor first makes
      decisions alone. This study extends the existing literature by explaining the
      mechanisms involved in preparedness for firsts.

PMID- 28744892
TI  - Decision-theoretic designs for a series of trials with correlated treatment
      effects using the Sarmanov multivariate beta-binomial distribution.
AB  - The motivation for the work in this article is the setting in which a number of
      treatments are available for evaluation in phase II clinical trials and where it
      may be infeasible to try them concurrently because the intended population is
      small. This paper introduces an extension of previous work on decision-theoretic
      designs for a series of phase II trials. The program encompasses a series of
      sequential phase II trials with interim decision making and a single two-arm
      phase III trial. The design is based on a hybrid approach where the final
      analysis of the phase III data is based on a classical frequentist hypothesis
      test, whereas the trials are designed using a Bayesian decision-theoretic
      approach in which the unknown treatment effect is assumed to follow a known prior
      distribution. In addition, as treatments are intended for the same population it
      is not unrealistic to consider treatment effects to be correlated. Thus, the
      prior distribution will reflect this. Data from a randomized trial of severe
      arthritis of the hip are used to test the application of the design. We show that
      the design on average requires fewer patients in phase II than when the
      correlation is ignored. Correspondingly, the time required to recommend an
      efficacious treatment for phase III is quicker.

PMID- 28744893
TI  - Tonotopic alterations in inhibitory input to the medial nucleus of the trapezoid
      body in a mouse model of Fragile X syndrome.
AB  - Hyperexcitability and the imbalance of excitation/inhibition are one of the
      leading causes of abnormal sensory processing in Fragile X syndrome (FXS). The
      precise timing and distribution of excitation and inhibition is crucial for
      auditory processing at the level of the auditory brainstem, which is responsible
      for sound localization ability. Sound localization is one of the sensory
      abilities disrupted by loss of the Fragile X Mental Retardation 1 (Fmr1) gene.
      Using triple immunofluorescence staining we tested whether there were alterations
      in the number and size of presynaptic structures for the three primary
      neurotransmitters (glutamate, glycine, and GABA) in the auditory brainstem of
      Fmr1 knockout mice. We found decreases in either glycinergic or GABAergic
      inhibition to the medial nucleus of the trapezoid body (MNTB) specific to the
      tonotopic location within the nucleus. MNTB is one of the primary inhibitory
      nuclei in the auditory brainstem and participates in the sound localization
      process with fast and well-timed inhibition. Thus, a decrease in inhibitory
      afferents to MNTB neurons should lead to greater inhibitory output to the
      projections from this nucleus. In contrast, we did not see any other significant
      alterations in balance of excitation/inhibition in any of the other auditory
      brainstem nuclei measured, suggesting that the alterations observed in the MNTB
      are both nucleus and frequency specific. We furthermore show that glycinergic
      inhibition may be an important contributor to imbalances in excitation and
      inhibition in FXS and that the auditory brainstem is a useful circuit for testing
      these imbalances.

PMID- 28744894
TI  - External national validation of the Leicester Self-Assessment score for Type 2
      diabetes using data from the English Longitudinal Study of Ageing.
AB  - AIMS: To validate the Leicester Self-Assessment score using a representative
      English dataset for detecting prevalent non-diabetic hyperglycaemia or
      undiagnosed Type 2 diabetes (defined as HbA1c >=6.0%) and for identifying those
      who may go on to develop Type 2 diabetes within 10 years. METHODS: Data were
      taken from the English Longitudinal Study of Ageing, a nationally representative
      dataset of people aged >=50 years. The area under the receiver-operator curve and
      performance metrics for the score at the recommended score threshold (>=16), were
      calculated for the outcomes of HbA1c >=42 mmol/mol (6.0%) at baseline and self
      reported Type 2 diabetes within 10 years in those aged 50-75 years at baseline.
      RESULTS: A total of 3203 individuals had a baseline HbA1c measurement, of whom
      247 (7.7%) had an HbA1c concentration >=42 mmol/mol (6.0%). The area under the
      receiver-operator curve was 69.4% (95% CI 66.0-72.9) for baseline HbA1c >=42
      mmol/mol. A total of 3550 individuals had diabetes status recorded at 10 years,
      of whom 324 (9.1%) were diagnosed with Type 2 diabetes within this time; the area
      under the receiver-operator curve for this outcome was 74.9% (95% CI 72.4-77.5).
      The score threshold of >=16 had a sensitivity of 89.2% (95% CI 85.3-92.4) and a
      specificity of 42.3% (95% CI 40.5-44.0) for Type 2 diabetes within 10 years.
      CONCLUSIONS: The Leicester Self-Assessment score is validated for use across
      England to identify people with non-diabetic hyperglycaemia or undiagnosed Type 2
      diabetes. Those with a high score are at high risk of developing diabetes in the
      future.

PMID- 28744895
TI  - Standing intraoral extractions of cheek teeth aided by partial crown removal in
      165 horses (2010-2016).
AB  - BACKGROUND: Diseased cheek teeth in horses often require invasive extraction
      techniques that carry a high rate of complications. Techniques and
      instrumentation were developed to perform partial crown removal to aid standing
      intraoral extraction of diseased cheek teeth in horses. OBJECTIVES: To analyse
      success rates and post-surgical complications in horses undergoing cheek teeth
      extraction assisted by partial crown removal. STUDY DESIGN: Retrospective cohort
      study. METHODS: This study included 165 horses with 194 diseased cheek teeth that
      were extracted orally assisted by partial crown removal between 2010 and 2016.
      Medical records were analysed, including case details, obtained radiographs,
      surgical reports and follow-up information. Follow-up information (>=2 months)
      was obtained for 151 horses (91.5%). There were 95 horses examined post
      operatively by the authors and, 16 horses by the referring veterinarian; in 40
      horses, post-operative follow up was obtained by informal telephone interviews
      with the owner. RESULTS: Successful standing intraoral extraction of cheek teeth
      was obtained in 164/165 horses (99.4%). Twenty-five of these horses (15.2%)
      required additional intraoral extraction methods to complete the extraction,
      including minimally invasive transbuccal approach (n = 21) and tooth sectioning
      (n = 4). There was one (0.6%) horse with intraoral extraction failure that
      required standing repulsion to complete the extraction. The intraoperative
      complication of fractured root tips occurred in 11/165 horses (6.7%). Post
      operative complications occurred in 6/165 horses (3.6%), including alveolar
      sequestra (n = 4), mild delay of alveolar healing at 2 months (n = 1), and
      development of a persistent draining tract secondary to a retained root tip (n =
      1). MAIN LIMITATIONS: Specialised instrumentation and additional training in the
      technique are recommended to perform partial crown removal in horses. CONCLUSION:
      Horses with cheek teeth extraction by partial crown removal have an excellent
      prognosis for a positive outcome. The term partial coronectomy is proposed for
      this technique.

PMID- 28744896
TI  - Elective repeat caesarean section versus induction of labour for women with a
      previous caesarean birth.
AB  - BACKGROUND: When a woman has had a previous caesarean birth and requires
      induction of labour for a subsequent pregnancy, two options are available for her
      care: an elective repeat caesarean and planned induction of labour. Although
      risks and benefits are associated with both elective repeat caesarean birth and
      planned induction of labour, current sources of information are limited to non
      randomised cohort studies, and studies designed in this way have significant
      potential for bias. Consequently, any conclusions based on results of these
      studies are limited in their reliability and should be interpreted with caution.
      OBJECTIVES: To assess, using the best available evidence, the benefits and harms
      of a policy of planned elective repeat caesarean section versus a policy of
      induction of labour for women with a previous caesarean birth who require
      induction of labour for a subsequent pregnancy. Primary outcomes include success
      of induction of labour, need for caesarean section, maternal and neonatal
      mortality, and maternal and neonatal morbidity. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Trials Register (31 May 2017) and planned to
      search reference lists of retrieved studies. SELECTION CRITERIA: Randomised
      controlled trials with reported data on comparison of outcomes in mothers and
      babies between women who planned an elective repeat caesarean section and women
      who planned induction of labour when a previous birth was performed by caesarean.
      Cluster trials and quasi-randomised trials were also eligible for inclusion. We
      would consider trials published only as abstracts if they provided enough
      information to meet review inclusion criteria. DATA COLLECTION AND ANALYSIS: We
      performed no data extraction. For future updates, if randomised controlled trials
      are identified, two review authors will independently assess trials for inclusion
      and risk of bias, and will extract data and check extracted data for accuracy.
      Review authors will assess the quality of the evidence using the GRADE approach.
      MAIN RESULTS: Review authors identified no randomised controlled trials. AUTHORS'
      CONCLUSIONS: Both planned elective repeat caesarean section and planned induction
      of labour for women with a prior caesarean birth are associated with benefits and
      harms. Evidence for these care practices has been drawn from non-randomised
      studies, which are associated with potential bias. Therefore, any results and
      conclusions presented must be interpreted with caution. Randomised controlled
      trials are required to provide the most reliable evidence regarding the benefits
      and harms of both planned elective repeat caesarean section and planned induction
      of labour for women with a previous caesarean birth.

PMID- 28744897
TI  - Furosemide suppresses ileal and colonic contractility via interactions with GABA
      A receptor in mice.
AB  - The loop diuretic furosemide has an action to inhibit Na+ -K+ -2Cl- co
      transporter at the thick ascending limb of Henle's loop resulting in diuresis.
      Furosemide also has the non-diuretic effects by binding to GABA-A receptor which
      may involve the gastrointestinal tract. The aim of this study was to investigate
      the effects of furosemide on smooth muscle contractions in mice ileum and
      proximal colon. Each intestinal segment suspended in an organ bath was connected
      to a force transducer. Signal output of mechanical activity was amplified and
      recorded for analysis using PowerLab System. After equilibration, the intestine
      was directly exposed to furosemide, GABA, GABA-A receptor agonist (muscimol), or
      muscarinic receptor antagonist (atropine). Furosemide (50, 100 and 500 MUmol L-1
      ) acutely reduced the amplitude of ileal and colonic contraction. In the ileum, 1
      mmol L-1 GABA and 10-60 MUmol L-1 muscimol significantly increased the amplitude,
      whereas in the colon, 50-100 mmol L-1 GABA and 60 MUmol L-1 muscimol decreased
      the contractions. The contractions were also significantly suppressed by
      atropine. To investigate the mechanisms underlying the inhibiting effect of
      furosemide, furosemide was added to the organ bath prior to the addition of
      muscimol or atropine. A comparison of furosemide combined with muscimol or
      atropine group and furosemide group showed no significant difference of the ileal
      contraction, but the amplitude of colonic contraction significantly decreased
      when compared to adding furosemide alone. These results suggest that furosemide
      can reduce the ileal and proximal colonic contraction mediated by blocking and
      supporting of GABA-A receptor, respectively, resulting in decreased acetylcholine
      release.

PMID- 28744898
TI  - Effect of chewing or compressing food on autonomic nervous activity in older
      adults.
AB  - OBJECTIVE: To determine if autonomic nervous activity increases in older people
      during mastication and how this activity is related to the softness of food. We
      hypothesised that the coefficient of variation of R-R intervals (CVRR), high
      frequency (HF) power, low-frequency (LF) power, LF/HF ratio and total power
      increase during chewing foods within the range of softness from moderate food to
      extremely soft food in older adults. MATERIALS AND METHODS: Participants were 20
      older volunteers (71-90 year old). CVRR and HF on the electrocardiogram (ECG)
      were used as indices of parasympathetic nervous activity. LF and the LF/HF ratio
      on the ECG were used as indices of sympathetic nervous activity. Total power,
      reflecting the level of autonomic nervous activity, was also measured.
      Participants were asked to chew gum with three different degrees of softness, or
      to compress extremely soft gum between their palate and tongue. RESULTS: There
      were significant differences in HF between at resting and all chewing/compressing
      conditions, but no significant differences relating to food softness. There were
      significant differences in total power between at resting and all
      chewing/compressing conditions, but no significant differences relating to food
      softness. There were no significant differences in LF, LF/HF and CVRR among all
      conditions. CONCLUSION: Autonomic nervous activity, especially parasympathetic
      activity in older adults, increased during chewing and compressing food when
      compared to activity while at rest. Within the range of food's softness from
      moderate to extreme soft, food's softness had no measurable effect on autonomic
      nervous activity.

PMID- 28744899
TI  - Selective serotonin reuptake inhibitors and dental implant failure-A significant
      concern in elders?
AB  - OBJECTIVE: Depression is a significantly prevalent health concern in geriatric
      populations. Selective serotonin reuptake inhibitor drugs (SSRI) are the most
      commonly prescribed antidepressant agents, with increasing rates of prescription.
      The present report aimed to present a concise review of the current understanding
      regarding SSRI effects on bone and dental implant outcomes. MATERIALS AND
      METHODS: A broad-based review and summary of literature pertaining to the effects
      of SSRI on bone metabolism and on dental implant survival was performed. RESULTS:
      The available literature indicates that serotonin plays a significant role in
      bone metabolism and experimental reports demonstrate adverse impacts of SSRI on
      multiple pathways of bone metabolism. Early clinical reports suggest detrimental
      effects of SSRI on dental implant survival. The type of SSRI drug, dosage and
      host-related genetic and metabolic factors could be potential modulating factors.
      There is a paucity of data regarding SSRI usage and dental implant survival
      specific to geriatric cohorts. CONCLUSION: As older individuals comprise a high
      risk group for both high oral rehabilitation and SSRI use, clinicians should be
      aware the potential association between SSRI and dental implant failures. Well
      designed investigations specific to geriatric cohorts are essential to understand
      the implications of SSRI use on dental implant prognosis.

PMID- 28744900
TI  - Mechanical and tactile incompatibilities cause reproductive isolation between two
      young damselfly species.
AB  - External male reproductive structures have received considerable attention as a
      cause of reproductive isolation (RI), because the morphology of these structures
      often evolves rapidly between populations. This rapid evolution presents the
      potential for mechanical incompatibilities with heterospecific female structures
      during mating and could thus prevent interbreeding between nascent species.
      Although such mechanical incompatibilities have received little empirical support
      as a common cause of RI, the potential for mismatch of reproductive structures to
      cause RI due to incompatible species-specific tactile cues has not been tested.
      We tested the importance of mechanical and tactile incompatibilities in RI
      between Enallagma anna and E. carunculatum, two damselfly species that diverged
      within the past ~250,000 years and currently hybridize in a sympatric region. We
      quantified 19 prezygotic and postzygotic RI barriers using both naturally
      occurring and laboratory-reared damselflies. We found incomplete mechanical
      isolation between the two pure species and between hybrid males and pure species
      females. Interestingly, in mating pairs for which mechanical isolation was
      incomplete, females showed greater resistance and refusal to mate with hybrid or
      heterospecific males compared to conspecific males. This observation suggests
      that tactile incompatibilities involving male reproductive structures can
      influence female mating decisions and form a strong barrier to gene flow in early
      stages of speciation.

PMID- 28744901
TI  - Input and Age-Dependent Variation in Second Language Learning: A Connectionist
      Account.
AB  - Language learning requires linguistic input, but several studies have found that
      knowledge of second language (L2) rules does not seem to improve with more
      language exposure (e.g., Johnson & Newport, 1989). One reason for this is that
      previous studies did not factor out variation due to the different rules tested.
      To examine this issue, we reanalyzed grammaticality judgment scores in Flege,
      Yeni-Komshian, and Liu's (1999) study of L2 learners using rule-related
      predictors and found that, in addition to the overall drop in performance due to
      a sensitive period, L2 knowledge increased with years of input. Knowledge of
      different grammar rules was negatively associated with input frequency of those
      rules. To better understand these effects, we modeled the results using a
      connectionist model that was trained using Korean as a first language (L1) and
      then English as an L2. To explain the sensitive period in L2 learning, the
      model's learning rate was reduced in an age-related manner. By assigning
      different learning rates for syntax and lexical learning, we were able to model
      the difference between early and late L2 learners in input sensitivity. The
      model's learning mechanism allowed transfer between the L1 and L2, and this
      helped to explain the differences between different rules in the grammaticality
      judgment task. This work demonstrates that an L1 model of learning and processing
      can be adapted to provide an explicit account of how the input and the sensitive
      period interact in L2 learning.

PMID- 28744902
TI  - Abstraction and the (Misnamed) Language Familiarity Effect.
AB  - Talkers are recognized more accurately if they are speaking the listeners' native
      language rather than an unfamiliar language. This "language familiarity effect"
      has been shown not to depend upon comprehension and must instead involve language
      sound patterns. We further examine the level of sound-pattern processing
      involved, by comparing talker recognition in foreign languages versus two
      varieties of English, by (a) English speakers of one variety, (b) English
      speakers of the other variety, and (c) non-native listeners (more familiar with
      one of the varieties). All listener groups performed better with native than
      foreign speech, but no effect of language variety appeared: Native listeners
      discriminated talkers equally well in each, with the native variety never
      outdoing the other variety, and non-native listeners discriminated talkers
      equally poorly in each, irrespective of the variety's familiarity. The results
      suggest that this talker recognition effect rests not on simple familiarity, but
      on an abstract level of phonological processing.

PMID- 28744903
TI  - Activity-dependent astrocyte swelling is mediated by pH-regulating mechanisms.
AB  - During neuronal activity in the mammalian brain, the K+ released into the
      synaptic space is initially buffered by the astrocytic compartment. In parallel,
      the extracellular space (ECS) shrinks, presumably due to astrocytic cell
      swelling. With the Na+ /K+ /2Cl- cotransporter and the Kir4.1/AQP4 complex not
      required for the astrocytic cell swelling in the hippocampus, the molecular
      mechanisms underlying the activity-dependent ECS shrinkage have remained
      unresolved. To identify these molecular mechanisms, we employed ion-sensitive
      microelectrodes to measure changes in ECS, [K+ ]o and [H+ ]o /pHo during
      electrical stimulation of rat hippocampal slices. Transporters and receptors
      responding directly to the K+ and glutamate released into the extracellular space
      (the K+ /Cl- cotransporter, KCC, glutamate transporters and G protein-coupled
      receptors) did not modulate the extracellular space dynamics. The HCO3-
      transporting mechanism, which in astrocytes mainly constitutes the electrogenic
      Na+ / HCO3- cotransporter 1 (NBCe1), is activated by the K+ -mediated
      depolarization of the astrocytic membrane. Inhibition of this transporter reduced
      the ECS shrinkage by ~25% without affecting the K+ transients, pointing to NBCe1
      as a key contributor to the stimulus-induced astrocytic cell swelling. Inhibition
      of the monocarboxylate cotransporters (MCT), like-wise, reduced the ECS shrinkage
      by ~25% without compromising the K+ transients. Isosmotic reduction of
      extracellular Cl- revealed a requirement for this ion in parts of the ECS
      shrinkage. Taken together, the stimulus-evoked astrocytic cell swelling does not
      appear to occur as a direct effect of the K+ clearance, as earlier proposed, but
      partly via the pH-regulating transport mechanisms activated by the K+ -induced
      astrocytic depolarization and the activity-dependent metabolism.

PMID- 28744904
TI  - Do mandibular complete dentures made using a neutral zone technique improve
      speech?-A pilot study.
AB  - OBJECTIVE: The aim of this study was to evaluate speech sound production (SSP) in
      older edentulous patients provided with two different types of mandibular
      complete dentures (MCDs; conventional vs neutral zone). BACKGROUND: Regarding the
      fact that complete dentures (CDs) affect SSP, it is unknown whether the set-up of
      the artificial teeth resulting from the neutral zone technique leads to a
      negative impact on SSP. MATERIALS AND METHODS: For 21 participants, a
      conventional MCD and a MCD using a modified neutral zone technique (neutral zone
      dentures) were fabricated. The SSP was described using a phonetically balanced
      text, which was recorded digitally and evaluated. RESULTS: No significant
      difference in SSP was observed. CONCLUSION: Within the limits of this study, it
      can be concluded that the application of the neutral zone technique in the
      mandible has no considerable impact on SSP.

PMID- 28744905
TI  - PNPLA3 rs738409 and Hepatotoxicity in Children With B-cell Acute Lymphoblastic
      Leukemia: A Validation Study in a Spanish Cohort.

PMID- 28744906
TI  - Effects of combination of mitiglinide with various oral antidiabetic drugs in
      streptozotocin-nicotinamide-induced type 2 diabetic rats and Zucker fatty rats.
AB  - We examined the effects of combining the rapid insulin secretagogue, mitiglinide,
      with various oral hypoglycaemic drugs including biguanides, pioglitazone, alpha
      glucosidase inhibitors, and sodium-glucose co-transporter 2 inhibitors in a rat
      model of type 2 diabetes. The oral glucose tolerance test (OGTT) using glucose,
      sucrose, or a liquid meal was used to compare the effects of mitiglinide with
      those of the four oral hypoglycaemic drugs and examine their combined effects on
      blood glucose levels and insulin secretion in the rat model. The combination of
      mitiglinide with other oral hypoglycaemic drugs suppressed the plasma glucose
      levels more than either agent did alone. Furthermore, the combination of these
      agents decreased insulin secretion more than mitiglinide did alone. These results
      indicate that mitiglinide is suitable for use in combination with other
      hypoglycaemic drugs because it inhibits postprandial hyperglycaemia by rapidly
      stimulating insulin secretion.

PMID- 28744907
TI  - Design and Hemocompatibility Analysis of a Double-Suction Injection Suspension
      Blood Pump Using Computational Fluid Dynamics Methods.
AB  - The blood pump has become a possible solution to heart diseases. For the
      prevention of device failure and hemocompatibility problems, a rotary pump with
      suspended bearing is a preferred solution. In our previous work, a novel
      injection suspension method has been introduced to levitate the rotor. The
      suspension method is totally passive. This study aims to apply this suspension
      method to a double-suction pump, and the property of the pump was investigated
      using computational fluid dynamics (CFD) methods. The flow field of the pump is
      simulated based on the SST k-omega turbulent model. The characteristic curves of
      the pump were calculated. At the nominal working point of 5 L/min, 100 mm Hg, the
      suspension force acting on the rotor was detected, which could reach 0.46 N with
      a gap of 150 um. We compared the pump with a previously developed single-suction
      injection pump to evaluate the blood compatibility of the double-suction design.
      The average scalar shear stress values were 3.13 Pa for the double-suction pump
      and 7.10 Pa for the single-suction pump. Larger volumes in the single-suction
      pump were exposed to shear stresses higher than 10 Pa. Thresholds for the von
      Willebrand factor cleavage, platelet activation, and hemolysis were defined to be
      9 Pa, 50 Pa, and 150 Pa, respectively. The volume fractions for the double
      suction pump are lower for all thresholds. The normalized index of hemolysis
      (NIH) values for the two pumps were calculated to be 0.008 g/100 L and 0.016
      g/100 L. Results proved that the double-suction pump has a better
      hemocompatibility compared with the single-suction pump.

PMID- 28744908
TI  - Lung cancer in a patient with predominantly short tremolite fibers in his lung.
AB  - The carcinogenicity of short tremolite fibers in human has not been cleared and
      has been argued hitherto. A lung cancer patient had worked at a gabbro quarry.
      Particles isolated from the excised lung parenchyma of the patient were measured
      for asbestos bodies (ABs) and asbestos fibers (AFs). The concentrations of ABs
      were 3964 AB/g dry lung, and AFs were 5.60 * 106 fibers/g dry lung (>5 um in
      length) and 22.5 * 106 fibers/g dry lung (>1 um in length). AFs were mostly
      tremolite fibers and under 7 um in length (mean length 4.0 um, standard deviation
      2.8 um). Almost all fibers were <10 um in length and an aspect ratio (AR) of
      <20:1 and >=3:1. The patient had never smoked. His wife, who had worked with him
      in the quarry, had died of pleural mesothelioma. This study strongly indicates
      that such short tremolite fibers will induce lung cancer and possibly
      mesothelioma in human.

PMID- 28744909
TI  - High diversity in neuropeptide immunoreactivity patterns among three closely
      related species of Dinophilidae (Annelida).
AB  - Neuropeptides are conserved metazoan signaling molecules, and represent useful
      markers for comparative investigations on the morphology and function of the
      nervous system. However, little is known about the variation of neuropeptide
      expression patterns across closely related species in invertebrate groups other
      than insects. In this study, we compare the immunoreactivity patterns of 14
      neuropeptides in three closely related microscopic dinophilid annelids
      (Dinophilus gyrociliatus, D. taeniatus and Trilobodrilus axi). The brains of all
      three species were found to consist of around 700 somata, surrounding a central
      neuropil with 3-5 ventral and 2-5 dorsal commissures. Neuropeptide
      immunoreactivity was detected in the brain, the ventral cords, stomatogastric
      nervous system, and additional nerves. Different neuropeptides are expressed in
      specific, non-overlapping cells in the brain in all three species. FMRFamide,
      MLD/pedal peptide, allatotropin, RNamide, excitatory peptide, and FVRIamide
      showed a broad localization within the brain, while calcitonin, SIFamide,
      vasotocin, RGWamide, DLamide, FLamide, FVamide, MIP, and serotonin were present
      in fewer cells in demarcated regions. The different markers did not reveal
      ganglionic subdivisions or physical compartmentalization in any of these
      microscopic brains. The non-overlapping expression of different neuropeptides may
      indicate that the regionalization in these uniform, small brains is realized by
      individual cells, rather than cell clusters, representing an alternative to the
      lobular organization observed in several macroscopic annelids. Furthermore,
      despite the similar gross brain morphology, we found an unexpectedly high
      variation in the expression patterns of neuropeptides across species. This
      suggests that neuropeptide expression evolves faster than morphology,
      representing a possible mechanism for the evolutionary divergence of behaviors.

PMID- 28744910
TI  - The illusion of informed consent.

PMID- 28744911
TI  - Antiproliferative Activity of Phenylpropanoids Isolated from Lagotis brevituba
      Maxim.
AB  - The aim of the present study was to evaluate the antiproliferative effect of
      phenylpropanoids isolated from the n-BuOH-soluble fraction of an ethanolic
      extract of Lagotis brevituba Maxim. The phenylpropanoids were identified as
      echinacoside, lagotioside, glucopyranosyl(1-6)martynoside, plantamoside, and
      verbascoside. Three of the compounds, lagotioside, glucopyranosyl(1
      6)martynoside, and plantamoside, were isolated from L. brevituba for the first
      time. The antiproliferative activity of the isolates was evaluated in human
      gastric carcinoma (MGC-803), human colorectal carcinoma (HCT116), human
      hepatocellar carcinoma (HepG2), and human lung cancer (HCT116) cells using an 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Plantamoside
      showed promising activity against MGC-803 cells, with a half maximal inhibitory
      concentration value of 37.09 MUM. The mechanism of the pro-apoptosis effect of
      plantamoside was then evaluated in MGC-803 cells. Changes in cell morphology,
      including disorganization of the architecture of actin microfilaments and
      formation of apoptotic bodies, together with cell cycle arrest in G2/M phases,
      were observed after treatment of plantamoside. The antiproliferative and pro
      apoptotic effects were associated with a decrease in the ratio of Bcl-2/Bax and
      reduced mitochondrial membrane potential, which was accompanied by the release of
      reactive oxygen species and Ca2+ into the cytoplasm. Taken together, the results
      indicated that plantamoside promotes apoptosis via a mitochondria-dependent
      mechanism. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28744912
TI  - Using the method of triads in the validation of a food frequency questionnaire to
      assess the consumption of fatty acids in adults.
AB  - BACKGROUND: It is of great value to develop valid instruments to estimate food
      consumption; for this purpose, the triads method has been applied in validation
      studies of dietary intake to evaluate the correlation between three measurements
      [food frequency questionnaire (FFQ), reference method and biomarker]. The main
      aim of the present study was to validate a FFQ for Brazilian adults by means of
      the method of triads by estimating the ingestion of total fatty acids based on
      the level of saturation. METHODS: The present study enrolled 152 Brazilian adults
      of both sexes, who were residents in the city of Vicosa, Brazil. The ingestion of
      total saturated, monounsaturated, polyunsaturated, trans, linoleic and linolenic
      fatty acids was assessed by means of a FFQ, two food records, and biomarkers,
      which were detected by gas chromatography. The validation coefficients were
      calculated using the method of triads and concordance was determined by Kappa
      statistics. RESULTS: The FFQ was considered an adequate dietary method, because,
      based on the validation coefficients, it estimates the intake of total fat
      (0.84), as well as linolenic (0.90) and linoleic acids (0.31). A high concordance
      rate was confirmed for all nutrients assessed by the FFQ and food records.
      Regarding the biomarkers, linolenic acid and linoleic acid presented greater
      concordance. CONCLUSIONS: According to the validation coefficients, the FFQ
      precisely estimated total fat, linolenic acid and linoleic acid contents.

PMID- 28744913
TI  - Aggression-related brain function assessed with the Point Subtraction Aggression
      Paradigm in fMRI.
AB  - The Point Subtraction Aggression Paradigm (PSAP) measures aggressive behavior in
      response to provocations. The aim of the study was to implement the PSAP in a
      functional neuroimaging environment (fMRI) and evaluate aggression-related brain
      reactivity including response to provocations and associations with aggression
      within the paradigm. Twenty healthy participants completed two 12-min PSAP
      sessions within the scanner. We evaluated brain responses to aggressive behavior
      (removing points from an opponent), provocations (point subtractions by the
      opponent), and winning points. Our results showed significant ventral and dorsal
      striatal reactivity when participants won a point and removed one from the
      opponent. Provocations significantly activated the amygdala, dorsal striatum,
      insula, and prefrontal areas. Task-related aggressive behavior was positively
      correlated with neural reactivity to provocations in the insula, the dorsal
      striatum, and prefrontal areas. Our findings suggest the PSAP within an fMRI
      environment may be a useful tool for probing aggression-related neural pathways.
      Activity in the amygdala, dorsal striatum, insula, and prefrontal areas during
      provocations is consistent with the involvement of these brain regions in
      emotional and impulsive behavior. Striatal reactivity may suggest an involvement
      of reward during winning and stealing points.

PMID- 28744914
TI  - Linguistic Constraints on Statistical Word Segmentation: The Role of Consonants
      in Arabic and English.
AB  - Statistical learning is often taken to lie at the heart of many cognitive tasks,
      including the acquisition of language. One particular task in which probabilistic
      models have achieved considerable success is the segmentation of speech into
      words. However, these models have mostly been tested against English data, and as
      a result little is known about how a statistical learning mechanism copes with
      input regularities that arise from the structural properties of different
      languages. This study focuses on statistical word segmentation in Arabic, a
      Semitic language in which words are built around consonantal roots. We
      hypothesize that segmentation in such languages is facilitated by tracking
      consonant distributions independently from intervening vowels. Previous studies
      have shown that human learners can track consonant probabilities across
      intervening vowels in artificial languages, but it is unknown to what extent this
      ability would be beneficial in the segmentation of natural language. We assessed
      the performance of a Bayesian segmentation model on English and Arabic, comparing
      consonant-only representations with full representations. In addition, we
      examined to what extent structurally different proto-lexicons reflect adult
      language. The results suggest that for a child learning a Semitic language,
      separating consonants from vowels is beneficial for segmentation. These findings
      indicate that probabilistic models require appropriate linguistic representations
      in order to effectively meet the challenges of language acquisition.

PMID- 28744916
TI  - Dioxygen Binding to Protonated Heme in the Gas Phase, an Intermediate Between
      Ferric and Ferrous Heme.
AB  - With a view to characterizing the influence of the electronic structure of the Fe
      atom on the nature of its bond with dioxygen (O2 ) in heme compounds, a study of
      the UV/Vis action spectra and binding energies of heme-O2 molecules has been
      undertaken in the gas phase. The binding reaction of protonated ferrous heme
      [FeII -hemeH]+ with O2 has been studied in the gas phase by determining the
      equilibrium of complexed [FeII -hemeH(O2 )]+ with uncomplexed protonated heme in
      an ion trap at controlled temperatures. The binding energy of O2 to the Fe atom
      of protonated ferrous heme was obtained from a van't Hoff plot. Surprisingly,
      this energy (1540+/-170 cm-1 , 18.4+/-2 kJ mol-1 ) is intermediate between those
      of ferric heme and ferrous heme. This result is interpreted in terms of a
      delocalization of the positive charge over the porphyrin cycle, such that the Fe
      atom bears a fractional positive charge. The resulting electron distribution on
      the Fe atom differs notably from that of a purely low-spin ferrous heme [FeII 
      heme(O2 )] complex, as deduced from its absorption spectrum. It also differs from
      that of ferric heme [FeIII -heme(O2 )]+ , as evidenced by the absorption spectra.
      Protonated heme creates a specific bond that cannot accommodate strong sigma
      donation.

PMID- 28744915
TI  - Characterization of Glcci1 expression in a subpopulation of lateral ganglionic
      eminence progenitors in the mouse telencephalon.
AB  - BACKGROUND: The lateral ganglionic eminence (LGE) in the ventral telencephalon is
      a diverse progenitor domain subdivided by distinct gene expression into a dorsal
      region (dLGE) that gives rise to olfactory bulb and amygdalar interneurons and a
      ventral region (vLGE) that gives rise to striatal projection neurons. The
      homeobox gene, Gsx2, is an enriched marker of the LGE and is expressed in a high
      dorsal to low ventral gradient in the ventricular zone (VZ) as development
      proceeds. Aside from Gsx2, markers restricted to the VZ in the dLGE and/or vLGE
      remain largely unknown. RESULTS: Here, we show that the gene and protein
      expression of Glucocorticoid-induced transcript 1 (Glcci1) has a similar dorsal
      to ventral gradient of expression in the VZ as Gsx2. We found that Glcci1 gene
      and protein expression are reduced in Gsx2 mutants, and are increased in the
      cortex after early and late Gsx2 misexpression. Moreover, Glcci1 expressing cells
      are restricted to a subpopulation of Gsx2 positive cells on the basal side of the
      VZ and co-express Ascl1, but not the subventricular zone dLGE marker, Sp8.
      CONCLUSIONS: These findings suggest that Glcci1 is a new marker of a
      subpopulation of LGE VZ progenitor cells in the Gsx2 lineage. Developmental
      Dynamics 247:222-228, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 28744917
TI  - The vocal sac of Hylodidae (Amphibia, Anura): Phylogenetic and functional
      implications of a unique morphology.
AB  - Anuran vocal sacs are elastic chambers that recycle exhaled air during
      vocalizations and are present in males of most species of frogs. Most knowledge
      of the diversity of vocal sacs relates to external morphology; detailed
      information on internal anatomy is available for few groups of frogs. Frogs of
      the family Hylodidae, which is endemic to the Atlantic Forest of Brazil and
      adjacent Argentina and Paraguay, have three patterns of vocal sac morphology-that
      is, single, subgular; paired, lateral; and absent. The submandibular musculature
      and structure of the vocal sac mucosa (the internal wall of the vocal sac) of
      exemplar species of this family and relatives were studied. In contrast to
      previous accounts, we found that all species of Crossodactylus and Hylodes
      possess paired, lateral vocal sacs, with the internal mucosa of each sac being
      separate from the contralateral one. Unlike all other frogs for which data are
      available, the mucosa of the vocal sacs in these genera is not supported
      externally by the mm. intermandibularis and interhyoideus. Rather, the vocal sac
      mucosa projects through the musculature and is free in the submandibular
      lymphatic sac. The presence of paired, lateral vocal sacs, the internal
      separation of the sac mucosae, and their projection through the m. interhyoideus
      are synapomorphies of the family. Furthermore, the specific configuration of the
      m. interhyoideus allows asymmetric inflation of paired vocal sacs, a feature only
      reported in species of these diurnal, stream-dwelling frogs.

PMID- 28744918
TI  - Essential oils and hydrophilic extracts from the leaves and flowers of Succisa
      pratensis Moench. and their biological activity.
AB  - OBJECTIVES: This study was undertaken to evaluate the antioxidant activity of
      methanol and water extracts from Succisa pratensis Moench (Dipsacaceae) leaves
      and flowers as well as the chemical composition of the essential oils found in
      them and the antimicrobial activity of the oils and extracts thereof. METHODS:
      The essential oils from S. pratensis leaves and flowers were analysed by the GC
      MS. The total phenolic content was determined with Folin-Ciocalteu, that of
      flavonoids with aluminium chloride and that of phenolic acids with Arnov's
      reagent. The antioxidant activity was investigated by the DPPH radical scavenging
      assay. Antimicrobial activity was studied in vitro against G-positive and G
      negative bacteria, and fungi using disc diffusion and broth microdilution
      methods. KEY FINDINGS: Eighty-six components of the leaf essential oil and 50 of
      the flower essential oil were identified. The main components of the leaf
      essential oil were 2-hexyl-1-octanol (5.76%) and heptacosane (5.53%), whereas
      hexadecanoic acid (16.10%), 8-octadecen-1-ol acetate (9.86%), methyl linolenate
      (8.58%), pentacosane (6.63%) and heptacosane (5.50%) were found in the flower
      essential oil. The essential oils exerted high antimicrobial activity (range:
      0.11 to >3.44mg/ml) against the following bacteria: Pseudomonas aeruginosa,
      Staphylococcus aureus and fungi: Trichophyton mentagrophytes, Candida albicans,
      whereas the methanol and water extracts showed moderate or weak activity. The
      strongest antioxidant activity was shown by methanol extracts from S. pratensis
      leaves, IC50 = 0.09 mg/ml. There was a positive correlation between the total
      phenolic content and the antimicrobial activity, while for the antioxidant
      effect, it was not observed. CONCLUSIONS: The results suggest great antibacterial
      activity of the oils and high antioxidant activity of the methanol extract and
      may justify the application in treating infections.

PMID- 28744919
TI  - Differential expression of insulin-like growth factor family members in immature
      cumulus-oocyte complexes from dairy cows with different genotypes.
AB  - It has been evident the improvement of in vitro embryo production (IVEP) in dairy
      cows. Nevertheless, it is known that differences in the number and quality of
      oocytes between taurine and zebu females impact the efficiency and economic
      viability of IVEP. As the insulin-like growth factor (IGF) system is related to
      follicular and oocyte development, we aimed to quantify mRNA abundance of IGF
      system members and pregnancy-associated plasma protein-A (PAPPA) in the cumulus
      oocyte complexes (COCs) of Gir, 1/2 Holstein * 1/2 Gir and Holstein cows. Four
      pools of 30 immature COCs from Gir, 1/2 Holstein * 1/2 Gir and Holstein cows were
      obtained by ovum pickup (OPU), and the oocytes and cumulus cells (CC) were
      mechanically separated and stored at -80 degrees C. Total RNA was extracted from
      pools of 30 oocytes and their respective CC. Expression of target genes was
      assessed by real-time RT-PCR. In oocytes, the abundance of IGFR1 mRNA was higher
      (p < .05) in Gir cows compared with the other breeds. In contrast, in CC, mRNA
      encoding IGF2 (p < .05), IGFR2 (p < .05) and IGFBP4 (p < .01) was higher in
      Holstein donors compared with Gir and 1/2 Holstein * 1/2 Gir cows. Additionally,
      the abundance of PAPPA mRNA was higher in oocytes (p < .001) and CC (p < .01) in
      Gir and 1/2 Holstein * 1/2 Gir cows compared with the Holstein donors. In
      conclusion, the higher abundance of PAPPA mRNA in the oocytes and CC from Gir and
      cross-breed donors combined with the low expression of IGFBP4 in the CC suggests
      an enhancement of the bioavailability of IGF-free when compared with Holstein
      COCs.

PMID- 28744921
TI  - Highly Transparent, Stretchable, and Self-Healing Ionic-Skin Triboelectric
      Nanogenerators for Energy Harvesting and Touch Applications.
AB  - Recently developed triboelectric nanogenerators (TENGs) act as a promising power
      source for self-powered electronic devices. However, the majority of TENGs are
      fabricated using metallic electrodes and cannot achieve high stretchability and
      transparency, simultaneously. Here, slime-based ionic conductors are used as
      transparent current-collecting layers of TENG, thus significantly enhancing their
      energy generation, stretchability, transparency, and instilling self-healing
      characteristics. This is the first demonstration of using an ionic conductor as
      the current collector in a mechanical energy harvester. The resulting ionic-skin
      TENG (IS-TENG) has a transparency of 92% transmittance, and its energy-harvesting
      performance is 12 times higher than that of the silver-based electronic current
      collectors. In addition, they are capable of enduring a uniaxial strain up to
      700%, giving the highest performance compared to all other transparent and
      stretchable mechanical-energy harvesters. Additionally, this is the first
      demonstration of an autonomously self-healing TENG that can recover its
      performance even after 300 times of complete bifurcation. The IS-TENG represents
      the first prototype of a highly deformable and transparent power source that is
      able to autonomously self-heal quickly and repeatedly at room temperature, and
      thus can be used as a power supply for digital watches, touch sensors, artificial
      intelligence, and biointegrated electronics.

PMID- 28744920
TI  - Anti-myocardial Ischemia Effect and Components of Litchi Pericarp Extracts.
AB  - Litchi (Litchi chinensis Sonn.) is a famous fruit in south China, and it is also
      effective for chest tightness or chest pain, irritability, flatulence, epigastric
      pain and neuralgic pain, hernia pain and testicular swelling, cough, etc. It is
      valued because a great amount of polyphenol was found in litchi pericarp. In this
      paper, we got litchi pericarp pure extract by a simple purification method, then
      evaluated its activity to clear oxygen free radicals in vitro, and evaluated its
      myocardial protection effect in vivo through acute myocardial ischemia rat model.
      The results showed that the pure extract had protective effect on myocardial
      ischemia injury in a certain dose-effect relationship, which reflected in the
      electrocardiogram, myocardial pathological morphology and other indicators such
      as cardiac function enzymes, serum and myocardial antioxidant capacity, and eNOS,
      Bcl-2 and Bax gene expression. Furthermore, we analyzed the components of pure
      extract by UPLC-MS, ESI-MS and NMR. The main components of PLPE were procyanidin
      which were identified as procyanidin B2(1), (-)-epicatechin(2), epicatechin
      (4beta -> 8,2beta -> O -> 7)-epicatechin-(4beta -> 8)-epicatechin(3), A-type
      procyanidin trimer(4), B-type procyanidin dimer(5) and procyanidin A2(6).This
      study proved that litchi pericarp extract may have antioxidant activity and
      cardioprotection effect. It suggested that litchi pericarp may be good for
      cardiovascular disease. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28744922
TI  - IFN-gammaR1 defects: Mutation update and description of the IFNGR1 variation
      database.
AB  - IFN-gamma signaling is essential for the innate immune defense against
      mycobacterial infections. IFN-gamma signals through the IFN-gamma receptor, which
      consists of a tetramer of two IFN-gammaR1 chains in complex with two IFN-gammaR2
      chains, where IFN-gammaR1 is the ligand-binding chain of the interferon-gamma
      receptor and IFN-gammaR2 is the signal-transducing chain of the IFN-gamma
      receptor. Germline mutations in the gene IFNGR1 encoding the IFN-gammaR1 cause a
      primary immunodeficiency that mainly leads to mycobacterial infections. Here, we
      review the molecular basis of this immunodeficiency in the 130 individuals
      described to date, and report mutations in five new individuals, bringing the
      total number to 135 individuals from 98 kindreds. Forty unique IFNGR1 mutations
      have been reported and they exert either an autosomal dominant or an autosomal
      recessive effect. Mutations resulting in premature stopcodons represent the
      majority of IFNGR1 mutations (60%; 24 out of 40), followed by amino acid
      substitutions (28%, 11 out of 40). All known mutations, as well as 287 other
      variations, have been deposited in the online IFNGR1 variation database
      (www.LOVD.nl/IFNGR1). In this article, we review the function of IFN-gammaR1 and
      molecular genetics of human IFNGR1.

PMID- 28744924
TI  - Breastfeeding as a public health responsibility: a review of the evidence.
AB  - BACKGROUND: Although intention to breastfeed in Western culture is high, many
      women stop breastfeeding before they are ready. From a physiological perspective,
      rates of primary milk insufficiency or contraindications to breastfeed should be
      low. However, numerous women encounter numerous barriers to breastfeeding, many
      of which occur at the social, cultural and political level and are therefore
      outside of maternal control. This review identifies and examines the impact of
      these barriers and considers how public health services should play a central
      role in creating a supportive breastfeeding environment. METHODS: A narrative
      review to synthesise themes in the literature was conducted, using Web of
      Science, PubMed and Science Direct. Barriers to breastfeeding at the societal
      rather than individual level were identified (e.g. in relation to health
      services, policies and economic factors). Only English language papers were
      included. RESULTS: Many barriers to breastfeeding exist at the societal rather
      than individual level. These influences are typically outside mothers' control.
      Five core themes were identified; the need for investment in (i) health services;
      (ii) population level health promotion; (iii) supporting maternal legal rights;
      (iv) protection of maternal wellbeing; and (v) reducing the reach of the breast
      milk substitute industry. CONCLUSIONS: Although individual support is important,
      breastfeeding must be considered a public health issue that requires investment
      at a societal level. Focusing solely on solving individual issues will not lead
      to the cultural changes needed to normalise breastfeeding. Countries that have
      adopted a multicomponent public heath strategy to increase breastfeeding levels
      have had significant success. These strategies must be emulated more widely.

PMID- 28744923
TI  - The role of T-type calcium channels in the subiculum: to burst or not to burst?
AB  - KEY POINTS: Pharmacological, molecular and genetic data indicate a prominent role
      of low-voltage-activated T-type calcium channels (T-channels) in the firing
      activity of both pyramidal and inhibitory interneurons in the subiculum.
      Pharmacological inhibition of T-channels switched burst firing with lower
      depolarizing stimuli to regular spiking, and fully abolished hyperpolarization
      induced burst firing. Our molecular studies showed that CaV 3.1 is the most
      abundantly expressed isoform of T-channels in the rat subiculum. Consistent with
      this finding, both regular-spiking and burst firing patterns were profoundly
      depressed in the mouse with global deletion of CaV 3.1 isoform of T-channels.
      Selective inhibition of T-channels and global deletion of CaV 3.1 channels
      completely suppressed development of long-term potentiation (LTP) in the CA1
      subiculum, but not in the CA3-CA1 pathway. ABSTRACT: Several studies suggest that
      voltage-gated calcium currents are involved in generating high frequency burst
      firing in the subiculum, but the exact nature of these currents remains unknown.
      Here, we used selective pharmacology, molecular and genetic approaches to
      implicate Cav3.1-containing T-channels in subicular burst firing, in contrast to
      several previous reports discounting T-channels as major contributors to
      subicular neuron physiology. Furthermore, pharmacological antagonism of T
      channels, as well as global deletion of CaV3.1 isoform, completely suppressed
      development of long-term potentiation (LTP) in the CA1-subiculum, but not in the
      CA3-CA1 pathway. Our results indicate that excitability and synaptic plasticity
      of subicular neurons relies heavily on T-channels. Hence, T-channels may be a
      promising new drug target for different cognitive deficits.

PMID- 28744925
TI  - Pharmacokinetic evaluation of oral itraconazole for antifungal prophylaxis in
      children.
AB  - Itraconazole is a first-generation triazole agent with an extended spectrum of
      activity; it is licensed in adults for superficial and systemic fungal
      infections; no recommendation has been yet established for use in children
      patients. Its variable and unpredictable oral bioavailability make it difficult
      to determine the optimal dosing regimen. Hence, therapeutic drug monitoring,
      highly available in clinical practice, may improve itraconazole treatment success
      and safety. The aim of the study was to describe in paediatrics the oral
      itraconazole pharmacokinetics, used for prophylaxis. Moreover, we evaluated the
      utility of its therapeutic drug monitoring in this cohort. A fully validated
      chromatographic method was used to quantify itraconazole concentration in plasma
      collected from paediatric patients, at the end of dosing interval. Associations
      between variables were tested using the Pearson test. Mann-Whitney U test has
      been used to probe the influence of categorical variables on continuous ones. Any
      predictive power of the considered variables was finally evaluated through
      univariate and multivariate linear and logistic regression analyses. A high inter
      individual variability was shown; ethnicity (beta coefficient, beta -0.161 and
      interval of confidence at 95%, IC -395.035; -62.383) and gender (beta 0.123 and
      IC 9.590; 349.395) remained in the final linear regression model with P value of
      .007 and .038, respectively. This study highlights that therapeutic drug
      monitoring is required to achieve an adequate target itraconazole serum exposure.

PMID- 28744926
TI  - Structural empowerment and burnout among Portuguese nursing staff: An explicative
      model.
AB  - AIMS: Kanter's structural empowerment model was used to assess the influence of
      access to opportunities, resources, information and support on core burnout
      through global empowerment in a nursing sample in Portugal. BACKGROUND: The
      empowerment experience increases the levels of nursing professionals'
      satisfaction and performance preventing the emergence of burnout. However, the
      relationship between structural empowerment and burnout has been scarcely studied
      in Portugal. METHODS: We conducted a cross-sectional correlational study
      assessing a final sample of 297 participants (62.13% response rate, 63.64%
      women). Model fit and mediation test were examined using structural equation
      modelling (path analysis). RESULTS: Access to opportunities and access to support
      had direct impact, through global empowerment, on core burnout, whereas access to
      resources had both direct and indirect impact on core burnout. CONCLUSIONS: The
      results validated the structural empowerment model and its application in nursing
      staff in Portugal. IMPLICATIONS FOR NURSING MANAGEMENT: Professional training
      plans, the development of formal and informal support networks, and the
      availability of resources increase the levels of empowerment and decrease the
      likelihood of experiencing burnout in nursing professionals.

PMID- 28744927
TI  - Hyphessobrycon platyodus (Teleostei: Characiformes), a new species from the Rio
      Madeira basin, Brazil, with comments on how multicuspid teeth relate to feeding
      habits in Characidae.
AB  - A new species of Hyphessobrycon is described from the Rio Juma, a tributary of
      the lower Rio Aripuana-Rio Madeira basin, Amazonas, Brazil. Hyphessobrycon
      platyodus can be distinguished from its congeners by the: presence of an
      elongated dorsal fin in adult males, 25-28 branched anal-fin rays and absence of
      dark blotches from the dorsal fin and caudal peduncle. The presence of
      multicuspid teeth in species of Characidae and its relation with feeding habits
      are briefly commented on.

PMID- 28744928
TI  - Evaluation of left atrial thrombus prior to catheter ablation of atrial
      fibrillation: Is it time for an individualized approach?

PMID- 28744929
TI  - Safety of union home care aides in Washington State.
AB  - INTRODUCTION: A rate-based understanding of home care aides' adverse occupational
      outcomes related to their work location and care tasks is lacking. METHODS:
      Within a 30-month, dynamic cohort of 43 394 home care aides in Washington State,
      injury rates were calculated by aides' demographic and work characteristics.
      Injury narratives and focus groups provided contextual detail. RESULTS: Injury
      rates were higher for home care aides categorized as female, white, 50 to <65
      years old, less experienced, with a primary language of English, and working
      through an agency (versus individual providers). In addition to direct
      occupational hazards, variability in workload, income, and supervisory/social
      support is of concern. CONCLUSIONS: Policies should address the roles and
      training of home care aides, consumers, and managers/supervisors. Home care
      aides' improved access to often-existing resources to identify, manage, and
      eliminate occupational hazards is called for to prevent injuries and address
      concerns related to the vulnerability of this needed workforce.

PMID- 28744930
TI  - What endocardial right ventricular pacing site shows better contractility and
      synchrony in children and adolescents?
AB  - AIMS: Right ventricular (RV) apical (RVA) pacing can induce left ventricular (LV)
      dyssynchrony, remodeling, and dysfunction in children with complete
      atrioventricular block (CAVB). We compared the functional outcome of RVA with RV
      alternative pacing sites (RVAPS), including para-Hisian, septal, and outflow
      tract sites. METHODS: This is a single-center, retrospective study. Data were
      collected before pacemaker implantation (transvenous leads), postoperatively, at
      6 months, and at 1-2-3-4 years. Electrocardiogram evaluation included QRS
      duration, axis, QTc/JTc, and QTc dispersion. Echocardiographic evaluation
      included 2-D/3-D assessment of ventricular dimensions (Z-score of LV end
      diastolic dimension), function (ejection fraction), and synchrony. RESULTS: From
      2009 to 2015, 55 patients with CAVB, aged 3-17 years, with or without other
      congenital heart defects, underwent RVAPS (30 patients, median age 11 years) or
      RVA (25 patients, median 12 years). All leads were positioned into the septum.
      Before implantation, no significant differences in parameters were observed,
      except for higher Z-score in RVAPS than in RVA. After implantation, at a median
      follow-up of 2.5 (range 1-6) years, the two groups showed no significant
      differences in LV dimensions, contractility, and synchrony. QRS intervals of
      RVAPS were significantly shorter than RVA. Clinical status was good and
      contractility/synchrony indexes were normal or adequate in all patients.
      CONCLUSIONS: In pediatric patients, RVAPS and RVA showed no significant
      differences in LV dimensions, contractility, and synchrony. Preimplantation
      dilated patients showed LV reverse remodeling. RVAPS demonstrated shorter QRS
      intervals. Therefore, septal pacing sites, either RVA or RVAPS, seem to determine
      good contractility and synchrony at a mid-term follow-up.

PMID- 28744931
TI  - Breakfast choice: An experiment combining a nutritional training workshop
      targeting adolescents and the promotion of unhealthy products.
AB  - A randomised control trial was conducted to determine changes in the food and
      drink choices of adolescents following their participation in a 50-min nutrition
      workshop. The experiment was conducted at 104 schools in Barcelona (126 classes,
      3,291 adolescents). Schools were randomly selected and stratified by district and
      by public or private status. The students were given three types of vouchers with
      different options regarding the type of food for which the vouchers could be
      exchanged (standard for healthy food and drink, two for one for unhealthy food,
      and two for one for unhealthy drink). Difference-in-differences linear models
      that control for individual, family, school or neighbourhood characteristics, and
      the influence of peers were applied. The probability of students' choosing
      unhealthy food and drink fell by 7.1% and 4.4%, respectively, following
      participation in the nutrition workshop. The promotion of unhealthy beverages
      counteracted the positive impact of the workshop on beverage choice.

PMID- 28744932
TI  - Introduction to graphene special edition.

PMID- 28744933
TI  - Do physical activity and body mass index modify the association between chronic
      musculoskeletal pain and insomnia? Longitudinal data from the HUNT study, Norway.
AB  - We investigated the prospective association between chronic musculoskeletal pain
      and risk of insomnia, and if leisure-time physical activity and body mass index
      modify this association. The study comprised historical data on 11 909 women and
      9938 men in the Norwegian HUNT study without sleep problems at baseline in 1995
      97 and followed-up for insomnia in 2006-08. Poisson regression was used to
      estimate adjusted risk ratios (RRs) with 95% confidence intervals (CIs). Compared
      to pain-free participants, any chronic pain was associated with a RR of insomnia
      of 2.27 (95% CI: 1.93, 2.66) in women and 1.58 (95% CI: 1.28, 1.95) in men,
      whereas reporting >=5 chronic pain sites gave RRs of 3.20 (95% CI: 2.60, 3.95)
      and 2.40 (95% CI: 1.76, 3.27), respectively. Analysis of joint effects showed
      that: (i) compared to pain-free physically active people, RRs in people with >=5
      chronic pain sites were 3.77 (95% CI: 2.42-5.85) if they were inactive and 2.76
      (95% CI: 2.29, 3.31) if they were active; and (ii) compared to pain-free people
      with normal weight, RRs in people with >=5 chronic pain sites were 3.52 (95% CI:
      2.81, 4.40) if they were obese and 2.93 (95% CI: 2.24, 3.84) if they had normal
      weight. In conclusion, chronic musculoskeletal pain increases the risk of
      insomnia, particularly among those who report several pain sites. Although there
      was no clear evidence of modifying effects, our results suggest that a healthy
      active lifestyle reduces the risk of insomnia in people with chronic
      musculoskeletal pain.

PMID- 28744934
TI  - Buttressing Effect as a Key Design Principle towards Highly Efficient Palladium/N
      Heterocyclic Carbene Buchwald-Hartwig Amination Catalysts.
AB  - The backbone substitution of the standard 1,3-bis(2,6-diisopropylphenyl)-2H
      imidazol-2-ylidene (IPr) ligand by dimethylamino groups was previously shown to
      induce a dramatic improvement in the catalytic efficiency of the corresponding Pd
      PEPPSI (pyridine-enhanced pre-catalyst preparation, stabilization, and
      initiation) pre-catalysts in N-arylation reactions. Herein, a thorough
      structure/activity study towards rationalizing this beneficial effect has been
      described. In addition to the previously reported IPrNMe2 and IPr(NMe2)2 ligands,
      the new IPrNiPr2 and IPr(NMe2,Cl) ligands, which bear one bulkier
      diisopropylamino group and a combination of dimethylamino and chloro
      substituents, respectively, have been designed and analyzed in the study. The
      influence of the backbone substitution was found to be steric in origin and is
      related to the well-known buttressing effect encountered in arene chemistry. The
      usefulness and versatility of this approach was demonstrated through the
      development of a highly efficient catalytic system for the challenging arylation
      of bulky alpha,alpha,alpha-trisubstituted primary amines. The optimized system
      based on the [PdCl(eta3 -cinnamyl)(IPr(NMe2)2 )] or [PdCl(eta3 
      cinnamyl)(IPrNiPr2 )] pre-catalysts operates under unprecedented mild conditions
      (catalyst loadings: 0.5-2 mol %, reaction temperatures: 40-60  degrees C) with a
      wide substrate scope.

PMID- 28744935
TI  - Emergency department presentations in infants: Predictors from an Australian
      birth cohort.
AB  - AIM: Infants under 12 months of age are disproportionately represented amongst
      emergency department (ED) presentations, and infants are more likely to be
      frequent ED users. This study aimed to describe and identify psychosocial
      predictors of ED presentation in infants. METHODS: A prospective birth cohort
      from Queensland and New South Wales (Environments for Healthy Living) was used to
      understand infant health service use. Baseline and 12-month questionnaire data
      pertaining to children born between 2006 and 2011 were used to identify
      predictors of ED presentation, using multiple regression analysis. RESULTS: Of
      the 2184 children in the cohort with available baseline and 12-month data, 579
      (27%) presented at least once to an ED during their first 12 months of life.
      Statistically significant predictors of ED presentation in the multivariate
      analysis included the mother having asthma (odds ratio (OR) 1.67, 95% confidence
      interval (CI) 1.15-2.39) and a higher Kessler-6 score (a measure of psychological
      distress) of the primary carer at baseline (OR 1.04, 95% CI 1.01-1.08). Maternal
      education level was not associated with ED presentations of infants. CONCLUSIONS:
      This study describes maternal and child factors of children who present to the ED
      in the first year of life. Factors related to an infant's support system were
      found to be predictors for an ED presentation in the first year of life. This
      study emphasises the need to review the maternal medical history and psychosocial
      situation. There may be benefits for health-care practitioners to take the
      opportunity (such as during routine childhood immunisation) to perform a brief
      screening tool (such as the Kessler-6) to understand psychological distress
      experienced by mothers. This may influence the likelihood of a child presenting
      to an ED within the first 12 months of life.

PMID- 28744936
TI  - Molecular combing reveals complex 4q35 rearrangements in Facioscapulohumeral
      dystrophy.
AB  - Facioscapulohumeral dystrophy (FSHD), one of the most common hereditary
      neuromuscular disorders, is associated with a complex combination of genetic
      variations at the subtelomeric 4q35 locus. As molecular diagnosis relying on
      Southern blot (SB) might be challenging in some cases, molecular combing (MC) was
      recently developed as an additional technique for FSHD diagnosis and exploration
      of the genomic organization of the 4q35 and 10q26 regions. In complement to the
      usual SB, we applied MC in a large cohort of 586 individuals with clinical FSHD.
      In 332 subjects, the two 4q alleles were normal in size, allowing exclusion of
      FSHD1 while we confirmed FSHD1 in 230 patients. In 14 patients from 10 families,
      we identified a recurrent complex heterozygous rearrangement at 4q35 consisting
      of a duplication of the D4Z4 array and a 4qA haplotype, irresolvable by the SB
      technique. In five families, we further identified variations in the SMCHD1 gene.
      Impact of the different mutations was tested using a minigene assay and we
      analyzed DNA methylation after sodium bisulfite modification and NGS sequencing.
      We discuss the involvement of this rearrangement in FSHD since all mutations in
      SMCHD1 are not associated with D4Z4 hypomethylation and do not always segregate
      with the disease.

PMID- 28744937
TI  - Differences in clinical intrusive thoughts between obsessive-compulsive disorder,
      generalized anxiety disorder, and hypochondria.
AB  - Differences and similarities between intrusive thoughts typical of obsessive
      compulsive disorder, generalized anxiety disorder, and hypochondriasis are
      relevant for their differential diagnosis, formulation, and psychological
      treatment. Previous research in non-clinical samples pointed out the relevance of
      some process variables, such as responsibility, guilt, or neutralization
      strategies. This research is aimed to investigate the differences and
      similarities between clinical obsessions, worries, and illness intrusions in some
      of these process variables. A second aim is to identify models based on these
      variables that could reliably differentiate between them. Three groups of
      patients with obsessive-compulsive disorder (n = 35; 60% women, mean age 38.57),
      generalized anxiety disorder (n = 36; 61.1% women, mean age 41.50), and
      hypochondriasis (n = 34; 70.6% women, mean age 31.59) were evaluated using the
      Cognitive Intrusions Questionnaire-Transdiagnostic Version (Romero-Sanchiz,
      Nogueira-Arjona, Godoy-Avila, Gavino-Lazaro, & Freeston, ). The results showed
      that some appraisals (e.g., responsibility or egodystonicity), emotions (e.g.,
      guilt or insecurity), neutralization strategies, and other variables (e.g.,
      verbal content or trigger from body sensation) are relevant for the
      discrimination between obsessions, worries, and illness intrusions. The results
      also showed 3 stable models based on these variables for the discrimination
      between these thoughts. The implication of these results in the diagnosis,
      formulation, and psychological treatment of obsessive-compulsive disorder,
      generalized anxiety disorder, and hypochondriasis is discussed.

PMID- 28744938
TI  - Integrative body-mind-spirit intervention for concurrent sleep and mood
      disturbances: sleep-specific daytime functioning mediates sleep and mood
      improvements.
AB  - Sleep disturbances and depressive symptoms are associated closely with daytime
      dysfunctions, yet few studies have investigated their temporal relationship in a
      randomized controlled trial. We investigated the inter-relationships among sleep,
      depressive symptoms and daytime functioning following an integrative body-mind
      spirit (I-BMS) intervention. One hundred and eighty-five participants (mean age
      55.28 years, 75.1% female) with co-existing sleep and depressive symptoms were
      randomized to I-BMS or waiting-list. Daytime functioning variables included the
      daytime dysfunction items of the Pittsburg Sleep Quality Index (PSQI-day),
      Somatic Symptom Inventory, Hospital Anxiety Depression Scale and Short Form
      Health Survey collected at baseline, post-treatment and 3-month follow-up. Sleep
      and depressive symptoms were measured by the sleep items of the PSQI (PSQI-night)
      and Center for Epidemiological Studies Depression Scale (excluding the sleep
      item) (CESD-M). Regression and path analyses were used to understand the role of
      daytime functioning in sleep and depressive symptoms. We found significant group
      and time effects on almost all daytime variables and significant group * time
      interactions on PSQI-day and somatic symptoms. The adjusted regression model
      showed that CESD-M was associated with all daytime variables. However, PSQI-night
      was associated only with PSQI-day. Path analyses indicated that PSQI-day bridged
      PSQI-night and CESD-M in a two-way direction after the I-BMS intervention. The
      conclusion was that, following I-BMS intervention, improvement in daytime
      functioning was related predominantly to improvement in depressive symptoms.
      Night-time sleep related only to daytime dysfunction that was specific to sleep
      disturbances. Therefore, 'sleep-specific daytime impairment' could be regarded as
      a major link from night-time sleep to depressive symptoms. More studies are
      required to understand the concept of 'sleep-specific daytime impairment'.

PMID- 28744939
TI  - Neural substrates of context- and person-dependent altruistic punishment.
AB  - Human altruistic behaviors are heterogeneous across both contexts and people,
      whereas the neural signatures underlying the heterogeneity remain to be
      elucidated. To address this issue, we examined the neural signatures underlying
      the context- and person-dependent altruistic punishment, conjoining event-related
      fMRI with both task-based and resting-state functional connectivity (RSFC).
      Acting as an impartial third party, participants decided how to punish norm
      violators either alone or in the presence of putative others. We found that the
      presence of others decreased altruistic punishment due to diffusion of
      responsibility. Those behavioral effects paralleled altered neural responses in
      the dorsal anterior cingulate cortex (dACC) and putamen. Further, we identified
      modulation of responsibility diffusion on task-based functional connectivity of
      dACC with the brain regions implicated in reward processing (i.e., posterior
      cingulate cortex and amygdala/orbital frontal cortex). Finally, the RSFC results
      revealed that (i) increased intrinsic connectivity strengths of the putamen with
      temporoparietal junction and dorsolateral PFC were associated with attenuated
      responsibility diffusion in altruistic punishment and (ii) increased putamen
      dorsomedial PFC connectivity strengths were associated with reduced
      responsibility diffusion in self-reported responsibility. Taken together, our
      findings elucidate the context- and person-dependent altruistic behaviors as well
      as associated neural substrates and thus provide a potential neurocognitive
      mechanism of heterogeneous human altruistic behaviors. Hum Brain Mapp 38:5535
      5550, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28744940
TI  - Report of the international symposiums at the 93rd Congress of Japan
      Gastroenterological Endoscopy Society in Osaka, 2017.

PMID- 28744941
TI  - Removal of Cell-Activating Substances Using Dialyzers With Various Permeability
      Profiles.
AB  - Despite multiple efforts to target an improvement in clinical outcomes of
      patients with end-stage renal disease, several challenges must still be
      addressed. Dialysis patients are at a high risk for complications, as reflected
      by increasing mortality rates. The objective of this study is to assess the
      impact of the application of dialyzers with varying permeability profiles on the
      removal of cell-activating substances from the blood of hemodialysis (HD)
      patients. Dialysate samples were collected using Revaclear 400 (RC) and MCO-Ci400
      (MCO-CI). Total protein and solute marker concentrations were determined for the
      concentrated sample. The response of tubular epithelial cells (TECs) to the
      dialysate samples was assessed via measurement of interleukin 6, cell viability,
      and morphology. Proteomic analysis of the dialysate samples was performed using
      liquid chromatography coupled to tandem mass spectrometry. Treatment of TECs with
      the MCO-CI dialysate resulted in significantly decreased cell viability compared
      with the RC dialysate. TECs incubated with samples from MCO-CI lost their typical
      brick-like shape and cell-cell connections. Proteomic analysis of dialysate
      samples indicated multiple pro-apoptotic and pro-inflammatory proteins,
      supporting the observed phenotype. Additionally, application of the MCO-CI
      dialyzer allowed for more efficient removal of proteins associated with advanced
      chronic kidney disease stages. Collectively, the use of dialyzer with a higher
      permeability profile enabled more efficient removal of cell-activating and toxic
      substances from the blood of HD patients. However, a further large-scale study is
      needed to address benefits and associated risks for patients.

PMID- 28744942
TI  - Utilization of Western medicine and traditional Chinese medicine among patients
      with Alzheimer's disease in Taiwan: a nationwide population-based study.
AB  - BACKGROUND AND PURPOSE: Large-scale studies of utilization of medical services
      among patients with Alzheimer's disease (AD) are lacking. We aimed to investigate
      the usage of Western medicine and traditional Chinese medicine (TCM) among these
      patients in Taiwan. METHODS: We analyzed one million samples from the National
      Health Insurance Research Database in Taiwan. Patients (n = 1814) newly diagnosed
      with AD in 2001-2010 were divided into TCM users (n = 528) and non-TCM users (n =
      1286). RESULTS: Compared with non-TCM users, TCM users were younger, had a higher
      female:male ratio and higher utilization rate of Western medicine. The median
      interval between diagnosis and the first TCM consultation was 7.92 months.
      Donepezil and rivastigmine were commonly prescribed medications. Chinese herbal
      medicine was the most popular treatment among TCM users. CONCLUSIONS: This study
      revealed the specific usage patterns of TCM and non-TCM medical services among
      patients with AD. The information could be used for improving the healthcare of
      patients with AD.

PMID- 28744943
TI  - Internal carotid, external carotid and vertebral artery blood flow responses to 3
      days of head-out dry immersion.
AB  - NEW FINDINGS: What is the central question of this study? The extent to which
      weightlessness associated with a fluid shift from the peripheral to the central
      circulation influences the blood flow in each cerebral artery remains unknown.
      The present study was designed to explore the effect of short-term weightlessness
      conditions on both anterior and posterior cerebral blood flow. What is the main
      finding and its importance? Short-term weightlessness affects both anterior and
      posterior cerebral vasculature. However, a heterogeneous cerebral blood flow
      response in each cerebral artery did not occur during 3 days of dry immersion. We
      have recently demonstrated that a heterogeneous cerebral blood flow (CBF)
      response in each cerebral artery might contribute to the maintenance of
      circulatory homeostasis in the brain. However, the extent to which weightlessness
      associated with a fluid shift from the peripheral to the central circulation
      influences the distribution of CBF in each cerebral artery remains unknown. We
      hypothesized that a dry immersion-induced fluid shift (weightlessness conditions)
      would cause a heterogeneous CBF response in each cerebral artery. During and
      after 3 days of dry immersion, the blood flows in the internal carotid (ICA),
      external carotid (ECA) and vertebral arteries (VA) were measured by Doppler
      ultrasonography using an 8 MHz linear transducer. Although the 3 days of dry
      immersion and the 2 days recovery period did not change the blood flow in each
      cerebral artery, the conductance in both ICA and VA decreased during dry
      immersion on days 2 and 3 (ICA, 2.95 and 3.23 ml min-1  mmHg-1 ; VA, 1.10 and
      1.05 ml min-1  mmHg-1 , respectively) from the baseline (ICA, 3.47 ml min-1  mmHg
      1 , P = 0.027; VA, 1.23 ml min-1  mmHg-1 , P = 0.004). In addition, Pearson
      correlation analysis demonstrated that the 3 days of dry immersion induced a
      decrease in cardiac output (P = 0.004) that was associated with changes in ICA (P
      = 0.046) and VA blood flow (P = 0.021), but not ECA blood flow (P = 0.466). These
      findings suggest that short exposures to weightlessness, acting via a cephalad
      redistribution of fluid volume and blood flow in the human body, influenced the
      cerebral vasculature in each cerebral artery but did not cause a heterogeneous
      CBF response in each cerebral artery.

PMID- 28744944
TI  - Violacein antimicrobial activity on Staphylococcus epidermidis and synergistic
      effect on commercially available antibiotics.
AB  - AIMS: The study aimed to assess whether violacein has antimicrobial activity on
      Staphylococcus epidermidis and synergistically modulates the action of
      commercially available antimicrobial drugs. METHODS AND RESULTS: Violacein showed
      excellent antimicrobial activity on biofilm-forming and nonbiofilm-forming S.
      epidermidis strains (ATCC 35984) (ATCC 12228), with bacteriostatic (MIC = 20 MUg
      ml-1 and 10 MUg ml-1 respectively) and bactericidal effects (MBC = 20 MUg ml-1
      for both strains), observed in short periods of exposure. The violacein
      bactericidal concentration led to S. epidermidis death after 2-3 h of exposure.
      Additionally, violacein synergistically modulated the activity of different
      antimicrobial classes on S. epidermidis ATCC 12228 (81.8%; n = 9) and on S.
      epidermidis ATCC 35984 (54.5%; n = 6), reducing the MIC of these antibiotics by
      up to 16-fold. CONCLUSION: Violacein shows excellent antimicrobial activity on S.
      epidermidis strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Violacein shows the
      potential for the development of a new drug for the treatment of infections
      caused by S. epidermidis.

PMID- 28744945
TI  - E-Mobility and the Energy Transition.
AB  - Since the reduction of greenhouse gases is the top priority of the Energy
      Transition, primary electricity should be converted to material energy carriers.
      In this way electricity can be "stored" and made accessible for other
      applications. This Essay focuses on the integration of mobility in the Energy
      Transition and the development of sustainable alternatives to electricity-based
      transportation.

PMID- 28744946
TI  - The effect of tocopheryl phosphates (TPM) on the development of atherosclerosis
      in apolipoprotein-E deficient mice.
AB  - alpha-Tocopheryl phosphate (TP) is a naturally occurring form of vitamin E found
      in the body. In the present study we compared the ability of an alpha-TP mixture
      (TPM) against a standard vitamin E supplement, alpha-tocopherol acetate (TA) on
      the development of atherosclerotic lesions in ApoE-deficient mice. Mice were
      maintained on either a normal chow diet for 24 weeks (Normal Diet), vs a group in
      which the final 8 weeks of the 24-week period mice were placed on a high fat
      (21%), high cholesterol (0.15%) challenge diet (HFHC), to exacerbate
      atherosclerotic lesion development.. The difference in these two control groups
      established the extent of the diet-induced atherosclerotic lesion development.
      Mice in the various treatment groups received either TA (300 mg/kg chow) or TPM
      (6.7-200 mg/kg chow) for 24 weeks, with TPM treatment resulting in dose-dependent
      significant reductions in atherosclerotic lesion formation and plasma levels of
      pro-inflammatory cytokines. TA-treated mice, with the tocopherol equivalent TPM
      dose (200 mg/kg chow), showed no significant reduction in plasma lipid levels or
      evidence for aortic lesion regression. At this TPM equivalent TA dose, a 44%
      reduction in aortic lesion formation was observed. In addition, these TPM treated
      mice, also showed a marked reduction in aortic superoxide formation and decreased
      circulating plasma levels of known pro-inflammatory markers IL-6, MCP-1, IL
      1beta, IFN-gamma and TNF-alpha. These findings indicate that TPM treatment slows
      progression of atherosclerotic lesions in ApoE-deficient mice with this effect
      potentially involving reduced oxidative stress and decreased inflammation.

PMID- 28744947
TI  - BMP-2 gene activated muscle tissue fragments for osteochondral defect
      regeneration in the rabbit knee.
AB  - BACKGROUND: Previously published data indicate that BMP-2 gene activated muscle
      tissue grafts can repair large bone defects in rats. This innovative abbreviated
      ex vivo gene therapy is appealing because it does not require elaborative and
      time-consuming extraction and expansion of cells. Hence, in the present study, we
      evaluated the potential of this expedited tissue engineering approach for
      regenerating osteochondral defects in rabbits. METHODS: Autologous muscle tissue
      grafts from female White New Zealand rabbits were directly transduced with an
      adenoviral BMP-2 vector or remained unmodified. Osteochondral defects in the
      medial condyle of rabbit knees were treated with either BMP-2 activated muscle
      tissue implants or unmodified muscle tissue or remained empty. After 13 weeks,
      repair of osteochondral defects was examined by biomechanical indentation testing
      and by histology/imunohistochemistry applying an extended O'Driscoll scoring
      system and histomorphometry. RESULTS: Biomechanical investigations revealed a
      trend towards slightly improved mechanical properties of the group receiving BMP
      2 activated muscle tissue compared to unmodified muscle treatment and empty
      defect controls. However, a statistically significant difference was noted only
      between BMP-2 muscle and unmodified muscle treatment. Also, histological
      evaluation resulted in slightly higher histological scores and improved collagen
      I/II ratio without statistical significance in the BMP-2 treatment group.
      Histomorphometry indicated enhanced repair of subchondral bone after treatment
      with BMP-2 muscle, with a significantly larger bone area compared to untreated
      defects. CONCLUSIONS: Gene activated muscle tissue grafts showed potential for
      osteochondral defect repair. There is room for improvement via the use of
      appropriate growth factor combinations.

PMID- 28744948
TI  - A subset of high Gleason grade prostate carcinomas contain a large burden of
      prostate cancer syndecan-1 positive stromal cells.
AB  - BACKGROUND: There is a pressing need to identify prognostic and predictive
      biomarkers for prostate cancer to aid treatment decisions in both early and
      advanced disease settings. Syndecan-1, a heparan sulfate proteoglycan, has been
      previously identified as a potential prognostic biomarker by multiple studies at
      the tissue and serum level. However, other studies have questioned its utility.
      METHODS: Anti-Syndecan-1 immunohistochemistry was carried out on 157 prostate
      tissue samples (including cancerous, adjacent normal tissue, and non-diseased
      prostate) from three independent cohorts of patients. A population of Syndecan-1
      positive stromal cells was identified and the number and morphological parameters
      of these cells quantified. The identity of the Syndecan-1-positive stromal cells
      was assessed by multiplex immunofluorescence using a range of common cell lineage
      markers. Finally, the burden of Syndecan-1 positive stromal cells was tested for
      association with clinical parameters. RESULTS: We identified a previously
      unreported cell type which is marked by Syndecan-1 expression and is found in the
      stroma of prostate tumors and adjacent normal tissue but not in non-diseased
      prostate. We call these cells Prostate Cancer Syndecan-1 Positive (PCSP) cells.
      Immunofluorescence analysis revealed that the PCSP cell population did not co
      stain with markers of common prostate epithelial, stromal, or immune cell
      populations. However, morphological analysis revealed that PCSP cells are often
      elongated and displayed prominent lamellipodia, suggesting they are an
      unidentified migratory cell population. Analysis of clinical parameters showed
      that PCSP cells were found with a frequency of 20-35% of all tumors evaluated,
      but were not present in non-diseased normal tissue. Interestingly, a subset of
      primary Gleason 5 prostate tumors had a high burden of PCSP cells. CONCLUSIONS:
      The current study identifies PCSP cells as a novel, potentially migratory cell
      type, which is marked by Syndecan-1 expression and is found in the stroma of
      prostate carcinomas, adjacent normal tissue, but not in non-diseased prostate. A
      subset of poor prognosis high Gleason grade 5 tumors had a particularly high PCSP
      cell burden, suggesting an association between this unidentified cell type and
      tumor aggressiveness.

PMID- 28744949
TI  - Identification of a new mineralized tissue in the notochord of reared Siberian
      sturgeon (Acipenser baerii).
AB  - In a study aiming to improve knowledge on the mineralization of the axial
      skeleton in reared Siberian sturgeon (Acipenser baerii Brandt, 1869), we
      discovered a new mineralized tissue within the notochord. To our knowledge, such
      a structure has never been reported in any vertebrate species with the exception
      of the pathological mineralization of the notochord remains in degenerative
      intervertebral disks of mammals. Here, we describe this enigmatic tissue using X
      ray microtomography, histological analyses and solid state NMR-spectroscopy. We
      also performed a 1-year monitoring of the mineral content (MC) of the notochord
      in relation with seasonal variations of temperature. In all specimens studied
      from 2-year-old juveniles onwards, this mineralized structure was found within a
      particular region of the notochord called funiculus. This feature first appears
      in the abdominal region then extends posteriorly with ageing, while the notochord
      MC also increases. The mineral phase is mainly composed of amorphous calcium
      phosphate, a small amount of which changes into hydroxyapatite with ageing. The
      putative role of this structure is discussed as either a store of minerals
      available for the phosphocalcic metabolism, or a mechanical support in a species
      with a poorly mineralized axial skeleton. A pathological feature putatively
      related to rearing conditions is also discussed.

PMID- 28744950
TI  - Neural signature of inattentional deafness.
AB  - Inattentional deafness is the failure to hear otherwise audible sounds (usually
      alarms) that may occur under high workload conditions. One potential cause for
      its occurrence could be an attentional bottleneck that occurs when task demands
      are high, resulting in lack of resources for processing of additional tasks. In
      this fMRI experiment, we explore the brain regions active during the occurrence
      of inattentional deafness using a difficult perceptual-motor task in which the
      participants fly through a simulated Red Bull air race course and at the same
      time push a button on the joystick to the presence of audio alarms. Participants
      were instructed to focus on the difficult piloting task and to press the button
      on the joystick quickly when they noticed an audio alarm. The fMRI results
      revealed that audio misses relative to hits had significantly greater activity in
      the right inferior frontal gyrus IFG and the superior medial frontal cortex.
      Consistent with an attentional bottleneck, activity in these regions was also
      present for poor flying performance (contrast of gates missed versus gates passed
      for the flying task). A psychophysiological interaction analysis from the IFG
      identified reduced effective connectivity to auditory processing regions in the
      right superior temporal gyrus for missed audio alarms relative to audio alarms
      that were heard. This study identifies a neural signature of inattentional
      deafness in an ecologically valid situation by directly measuring differences in
      brain activity and effective connectivity between audio alarms that were not
      heard compared to those that were heard. Hum Brain Mapp 38:5440-5455, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28744951
TI  - A meso-meso beta-beta beta-beta Triply Linked Subporphyrin Dimer.
AB  - A meso-meso beta-beta beta-beta triply linked subporphyrin dimer 6 was
      synthesized by stepwise reductive elimination of beta-to-beta doubly PtII 
      bridged subporphyrin dimer 9. Dimer 6 was characterized by spectroscopic and
      electrochemical measurements, theoretical calculations, and picosecond time
      resolved transient absorption spectroscopy. X-ray diffraction analysis reveals
      that 6 has a bowl-shaped structure with a positive Gaussian curvature. Despite
      the curved structure, 6 exhibits a remarkably red-shifted absorption band at 942
      nm and a small electrochemical HOMO-LUMO gap (1.35 eV), indicating an effectively
      conjugated pi-electronic network.

PMID- 28744952
TI  - Effects of free radical initiators on polyethylene glycol dimethacrylate hydrogel
      properties and biocompatibility.
AB  - Many studies have utilized Irgacure 2959 photopolymerized poly(ethylene glycol)
      (PEG) hydrogels for tissue engineering application development. Due to the
      limited penetration of ultraviolet light through tissue, Irgacure 2959
      polymerized hydrogels are not suitable for use in tissues where material
      injection is desirable, such as the spinal cord. To address this, several free
      radical initiators (thermal initiator VA044, ammonium persulfate (APS)/TEMED
      reduction-oxidation reaction, and Fenton chemistry) are evaluated for their
      effects on the material and mechanical properties of PEG hydrogels compared with
      Irgacure 2959. To emulate the effects of endogenous thiols on in vivo
      polymerization, the effects of chain transfer agent (CTA) dithiothreitol on
      gelation rates, material properties, Young's and shear modulus, are examined.
      Mouse embryonic stem cells and human induced pluripotent stem cell derived neural
      stem cells were used to investigate the cytocompatibility of each polymerization.
      VA044 and Fenton chemistry polymerization of PEG hydrogels both had gelation
      rates and mechanical properties that were highly susceptible to changes in CTA
      concentration and showed poor cytocompatibility. APS/TEMED polymerized hydrogels
      maintained consistent gelation rates and mechanical properties at high CTA
      concentration and had a similar cytocompatibility as Irgacure 2959 when cells
      were encapsulated within the PEG hydrogels. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 105A: 3059-3068, 2017.

PMID- 28744953
TI  - A Three-Year Longitudinal Study of Reading and Spelling Difficulty in Chinese
      Developmental Dyslexia: The Matter of Morphological Awareness.
AB  - In the present study, we used a three-time point longitudinal design to
      investigate the associations of morphological awareness to word reading and
      spelling in a small group of those with and without dyslexia taken from a larger
      sample of 164 Hong Kong Chinese children who remained in a longitudinal study
      across ages 6, 7 and 8. Among those 164 children, 15 had been diagnosed as having
      dyslexia by professional psychologists, and 15 other children manifested average
      reading ability and had been randomly selected from the sample for comparison.
      All children were administered a battery of tasks including Chinese character
      recognition, word dictation, morphological awareness, phonological awareness and
      rapid automatized naming. Multivariate analysis of variance and predictive
      discriminate analysis were performed to examine whether the dyslexic children
      showed differences in the cognitive-linguistic tasks in comparison with controls.
      Results suggested that the dyslexic groups had poorer performance in
      morphological awareness and RAN across all 3 years. However, phonological
      awareness was not stable in distinguishing the groups. Findings suggest that
      morphological awareness is a relatively strong correlate of spelling difficulties
      in Chinese, but phonological awareness is not. Copyright (c) 2017 John Wiley &
      Sons, Ltd.

PMID- 28744954
TI  - Lichen amyloidosis involving the scalp.

PMID- 28744955
TI  - Cortical connectivity modulation during sleep onset: A study via graph theory on
      EEG data.
AB  - Sleep onset is characterized by a specific and orchestrated pattern of frequency
      and topographical EEG changes. Conventional power analyses of
      electroencephalographic (EEG) and computational assessments of network dynamics
      have described an earlier synchronization of the centrofrontal areas rhythms and
      a spread of synchronizing signals from associative prefrontal to posterior areas.
      Here, we assess how "small world" characteristics of the brain networks, as
      reflected in the EEG rhythms, are modified in the wakefulness-sleep transition
      comparing the pre- and post-sleep onset epochs. The results show that sleep onset
      is characterized by a less ordered brain network (as reflected by the higher
      value of small world) in the sigma band for the frontal lobes indicating stronger
      connectivity, and a more ordered brain network in the low frequency delta and
      theta bands indicating disconnection on the remaining brain areas. Our results
      depict the timing and topography of the specific mechanisms for the maintenance
      of functional connectivity of frontal brain regions at the sleep onset, also
      providing a possible explanation for the prevalence of the frontal-to-posterior
      information flow directionality previously observed after sleep onset. Hum Brain
      Mapp 38:5456-5464, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28744956
TI  - Care of the dying: a qualitative exploration of Foundation Year doctors'
      experiences.
AB  - CONTEXT: Foundation Year doctors (FYs), who are newly qualified, are expected to
      provide care for dying patients. Experiences at this early mandatory stage of
      training may form the foundation for future encounters, but little is documented
      about what these experiences involve. The aim of this research was to explore the
      experiences of FYs in caring for the dying, using the recently published
      Priorities for Care of the Dying Person as a conceptual framework, to identify
      areas for improvement in education and clinical practice. METHODS: Semi
      structured group and individual interviews were conducted to explore the
      experiences of FYs and how these relate to the five aspects of Priorities for
      Care of the Dying Person: 'recognise', 'communicate', 'involve', 'support' and
      'plan and do'. All FYs in the North Yorkshire and East Coast Foundation School
      (n=335) were invited to participate and 47 FYs were recruited from five sites
      through convenience sampling and snowballing. Recordings were transcribed
      verbatim and a framework analysis approach was used with the published Priorities
      for Care of the Dying Person guidelines as a conceptual framework. RESULTS: Five
      main themes and 13 subthemes emerged from the data. The five main themes, which
      mapped to the conceptual framework, were: recognition that the patient is dying;
      communication with the patient, family and other staff; involvement of the
      patient and family in their care; support for the dying person and their family;
      and planning and carrying out good care of the dying. Examples of when things are
      done poorly or done well were shared, giving context to experience. CONCLUSIONS:
      Areas for improvement were identified around all five main themes. These will be
      useful for informing those involved in undergraduate and foundation training on
      how to improve the experiences of Foundation Year doctors and thereby improve
      patient care.

PMID- 28744957
TI  - Glandular odontogenic cyst: An updated analysis of 169 cases reported in the
      literature.
AB  - OBJECTIVE: To integrate the available data published on glandular odontogenic
      cyst (GOC) into a comprehensive analysis of its clinical/radiological and
      histopathological features. METHODS: An electronic search was undertaken in
      May/2017. Eligibility criteria included publications having enough
      clinical/radiological/histological information to confirm the diagnosis. RESULTS:
      Fifty-eight publications (169 GOCs) were included. The lesion was slightly more
      prevalent in men than in women. There was a high prevalence in the fifty/sixth
      decades of life, in the anterior regions, and in mandibles. Lesions were commonly
      associated with bone expansion (73%) and unilocular radiological appearance
      (61.5%). GOC was found to be associated with tooth displacement or an unerupted
      tooth (30.9%), cortical bone perforation (26%), presence of clinical symptoms
      (24.3%), root resorption (13.9%). Microscopic parameters most commonly were
      observed in GOCs-in at least 95% of the lesions: presence of hobnail cells,
      intraepithelial microcysts, epithelial lining with variable thickness. The
      presence of apocrine snouting was the microscopic parameter less often found
      (40.4%). CONCLUSION: Although the recurrence rate of GOCs is not as high as
      previously believed, it is a relevant phenomenon (21.6%). Adjunctive procedures
      after enucleation should be considered. None of the clinical/radiological and
      histopathological features evaluated had a statistically significant effect on
      the recurrence rate.

PMID- 28744958
TI  - Post-extraction implant placement into infected versus non-infected sites: A
      multicenter retrospective clinical study.
AB  - PURPOSE: The aim of this study was to assess whether immediate implant placement
      into post-extraction sites presenting a chronic infection poses a greater risk of
      implant failure than immediate placement in non-infected sites. MATERIALS AND
      METHODS: Records of patients who underwent extraction and immediate implant
      placement into both infected and non-infected sites from January 1998 to
      September 2014 at 5 different dental centers were considered for inclusion.
      Included records were subjected to statistical analysis of survival rates, along
      with a number of other patient-, implant-, surgery-, and prosthesis-related
      variables. RESULTS: The inclusion criteria were met by 369 patients who received
      a total of 527 implants. The follow-up averaged 53.2 months (range 0.9-158.3) for
      implants placed into non-infected sockets (N = 334) and 50.1 months (range 1.6
      146.1) for those placed into infected sites (N = 193). Seven implants failed in
      non-infected sites and 3 in infected ones. All failures occurred within 1 year of
      placement. Cumulative implant survival rate for non-infected and infected sites
      was, respectively, 97.9% +/- 0.8% and 98.4% +/- 0.9%, being not significantly
      different (P = .66). None of the investigated variables affected the outcome.
      CONCLUSIONS: Placement of implants into periodontally or endodontically infected
      sites immediately after tooth extraction is a safe option, even when the implants
      are loaded immediately or early.

PMID- 28744960
TI  - Emerging combination endocrine therapies for advanced breast cancer.

PMID- 28744959
TI  - Predicting appropriate shocks in patients with heart failure: Patient level meta
      analysis from SCD-HeFT and MADIT II.
AB  - BACKGROUND: No precise tools exist to predict appropriate shocks in patients with
      a primary prevention ICD. We sought to identify characteristics predictive of
      appropriate shocks in patients with a primary prevention implantable cardioverter
      defibrillator (ICD). METHODS: Using patient-level data from the Multicenter
      Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac
      Death in Heart Failure Trial (SCD-HeFT), we identified patients with any
      appropriate shock. Clinical and demographic variables were included in a logistic
      regression model to predict appropriate shocks. RESULTS: There were 1,463
      patients randomized to an ICD, and 285 (19%) had >=1 appropriate shock over a
      median follow-up of 2.59 years. Compared with patients without appropriate ICD
      shocks, patients who received any appropriate shock tended to have more severe
      heart failure. In a multiple logistic regression model, predictors of appropriate
      shocks included NYHA class (NYHA II vs. I: OR 1.65, 95% CI 1.07-2.55; NYHA III
      vs. I: OR 1.74, 95% CI 1.10-2.76), lower LVEF (per 1% change) (OR 1.04, 95% CI
      1.02-1.06), absence of beta-blocker therapy (OR 1.61, 95% CI 1.23-2.12), and
      single chamber ICD (OR 1.67, 95% CI 1.13-2.45). CONCLUSION: In this meta-analysis
      of patient level data from MADIT-II and SCD-HeFT, higher NYHA class, lower LVEF,
      no beta-blocker therapy, and single chamber ICD (vs. dual chamber) were
      significant predictors of appropriate shocks.

PMID- 28744961
TI  - The LexA transcription factor regulates fatty acid biosynthetic genes in the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - Specific transcription factors have been identified in various heterotrophic
      bacterial species that regulate the sets of genes required for fatty acid
      metabolism. Here, we report that expression of the fab genes, encoding fatty acid
      biosynthetic enzymes, is regulated by the global regulator LexA in the
      photoautotrophic cyanobacterium Synechocystis sp. PCC 6803. Sll1626, an ortholog
      of the well-known LexA repressor involved in the SOS response in heterotrophic
      bacteria, was isolated from crude extracts of Synechocystis by DNA affinity
      chromatography, reflecting its binding to the upstream region of the acpP-fabF
      and fabI genes. An electrophoresis mobility shift assay revealed that the
      recombinant LexA protein can bind to the upstream region of each fab gene tested
      (fabD, fabH, fabF, fabG, fabZ and fabI). Quantitative RT-PCR analysis of the wild
      type and a lexA-disrupted mutant strain suggested that LexA acts as a repressor
      of the fab genes involved in initiation of fatty acid biosynthesis (fabD, fabH
      and fabF) and the first reductive step in the subsequent elongation cycle (fabG)
      under normal growth conditions. Under nitrogen-depleted conditions,
      downregulation of fab gene expression is partly achieved through an increase in
      LexA-repressing activity. In contrast, under phosphate-depleted conditions, fab
      gene expression is upregulated, probably due to the loss of repression by LexA.
      We further demonstrate that elimination of LexA largely increases the production
      of fatty acids in strains modified to secrete free fatty acids.

PMID- 28744962
TI  - Inverse estimation of cardiac activation times via gradient-based optimization.
AB  - Computational modeling may provide a quantitative framework for integrating
      multiscale data to gain insight into mechanisms of heart disease, identify and
      test pharmacological and electrical therapy and interventions, and support
      clinical decisions. Patient-specific computational cardiac models can help guide
      such procedures, and cardiac inverse modeling is a promising alternative to
      adequately personalize these models. Indeed, full cardiac inverse modeling is
      currently becoming computationally feasible; however, fundamental work to assess
      the feasibility of emerging techniques is still needed. In this study, we use a
      partial differential equation-constrained optimal control approach to numerically
      investigate the identifiability of an initial activation sequence from synthetic
      (partial) observations of the extracellular potential using the bidomain
      approximation and 2D representations of cardiac tissue. Our results demonstrate
      that activation times and duration of several stimuli can be recovered even with
      high levels of noise, that it is sufficient to sample the observations at the
      electrocardiogram-relevant sampling frequency of 1 kHz, and that spatial
      resolutions that are coarser than the standard in electrophysiological
      simulations can be used. The optimization of activation times is still effective
      when synthetic data are generated with a different cell membrane kinetics model
      than optimized for. The findings thus indicate that the presented approach has
      potential for finding activation sequences from clinical data modalities, as an
      extension to existing cardiac imaging approaches.

PMID- 28744963
TI  - Association of incretin receptors genetic polymorphisms with type 2 diabetes
      mellitus in Egyptian patients.
AB  - BACKGROUND: Incretins have opened a new era in type 2 diabetes mellitus (T2DM)
      pathogenesis. The present study aimed to assess whether there is an association
      between GIPR rs2302382, GIPR rs1800437 and GLP-1R rs367543060 polymorphisms with
      T2DM or not and also to determine the effect of these polymorphisms on gastric
      inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels. METHODS:
      One hundred and fifty T2DM patients and 150 healthy controls were included in the
      study. Polymorphisms of GIPR rs1800437, GIPR rs2302382 and GLP-1R rs367543060
      were genotyped using restriction fragment length polymorphism (RFLP)-polymerase
      chain reaction (PCR), multiplex allele-specific PCR and RFLP-PCR respectively.
      GIP and GLP levels were measured by an enzyme-linked immunosorbent assay.
      RESULTS: We found a significant association of both the homozygous AA and the
      minor allele A of GIPR rs2302382 with T2DM. The frequency of haplotype
      C(rs2302382) G(rs1800437) was significantly higher in controls than in diabetics;
      odds ratio (95% confidence interval): 1.99 (1.44-2.75) (p < 0.001), whereas the
      haplotype A(rs2302382) C(rs1800437) was significantly higher in patients than
      controls. We did not find any association of GLP-1R rs367543060 polymorphism with
      T2DM. We found a significant increase in serum total GIP and a significant
      decrease of GLP-1 levels in T2DM patients. CONCLUSIONS: We reveal for the first
      time an association between the GIPR rs2302382 polymorphism and T2DM in
      Egyptians. Yet, there was no significant association of GIPR rs1800437 or GLP-1R
      rs367543060 with T2DM risk. The haplotype A (rs2302382) C (rs1800437) was
      associated with an increased risk of T2DM. Furthermore, there was a significant
      increase of GIP and a significant decrease of GLP-1 levels when diabetic patients
      were compared with controls. An important finding was that there was a
      relationship between both GIPR rs2302382 and rs1800437 variants and their cognate
      ligand levels.

PMID- 28744964
TI  - Specification of Larval Axes of Partial Embryos in the Temnopleurid Temnopleurus
      toreumaticus and the Strongylocentroid Hemicentrotus pulcherrimus.
AB  - Many sea urchins, including the strongylocentroid Hemicentrotus pulcherrimus,
      produce an amniotic cavity on the left for adult rudiment formation at the late
      larval stage. In contrast, temnopleurids form a cell mass at the early larval
      stage instead of an amniotic cavity. Although the mechanisms establishing left
      right polarity of the amniotic cavity involve cell-cell interactions and
      signaling pathways, corresponding pathways for the cell mass are unknown. We
      analyzed the effects of blastomere isolation on the specification of larval axes
      in the temnopleurid Temnopleurus toreumaticus and compared them to those in H.
      pulcherrimus. Blastomere isolation at the two- or four-cell stages in T.
      toreumaticus disturbed the location of the cell mass and adult rudiment in
      approximately 10-20% of specimens. In contrast, isolation at the two-cell stage
      in H. pulcherrimus caused the left-right polarity to become random. When
      blastomeres isolated at the two-cell stage were cultured as pairs, approximately
      20% of pairs had atypical polarity in both species. Following isolation at the
      four-cell stage, 71.4% of quartets produced larvae with atypical polarity in T.
      toreumaticus. Thus, cell-cell interaction between two daughter blastomeres after
      the second cleavage may be involved in the mechanism determining left-right
      polarity. Dye injection into a blastomere and subsequent observations indicated
      that the location of the boundary of the first cleavage showed similar patterns
      in both species. These observations suggest that species-specific mechanisms
      establish the larval axes and blastomeres at the two- and four-cell stages
      redistribute their cytoplasm, forming gradients that establish left-right
      polarity.

PMID- 28744965
TI  - Expression of BrpA in Streptococcus mutans is regulated by FNR-box mediated
      repression.
AB  - Our previous studies showed that brpA in Streptococcus mutans, which encodes a
      member of the LytR-CpsA-Psr family of proteins, can be co-transcribed with brpB
      upstream as a bicistronic operon, and the intergenic region also has strong
      promoter activity. To elucidate how brpA expression is regulated, the promoter
      regions were analyzed using polymerase chain reaction-based deletions and site
      directed mutagenesis and a promoterless luciferase gene as a reporter. Allelic
      exchange mutagenesis was also used to examine genes encoding putative trans
      acting factors, and the impact of such mutations on brpA expression was analyzed
      by reporter assays. Multiple elements in the short brpA promoter (nucleotide -1
      to -344 relative to start cordon ATG) were shown to have a major impact on brpA
      expression, including an FNR-box, for a putative binding site of an FNR-type of
      transcriptional regulator. When compared with the intact brpA promoter, mutations
      of the highly conserved nucleotides in FNR-box from TTGATgtttAcCtt to
      TTACAgaaaGtTac resulted in 1362-fold increases of luciferase activity (P < .001),
      indicative of the FNR-box-mediated repression as a major mechanism in regulation
      of brpA expression. When luciferase reporter was fused to the upstream brpBA
      promoter (nucleotides -784 to -1144), luciferase activity was decreased by 4.5
      fold (P < .001) in the brpA mutant, TW14D, and by 67.7-fold (P < .001) in the
      brpB mutant, JB409, compared with the wild-type, UA159. However, no such effects
      were observed when the reporter gene was fused to the short brpA promoter and its
      derivatives. These results also suggest that brpA expression in S. mutans is auto
      regulated through the upstream brpBA promoter.

PMID- 28744966
TI  - Social media and organ donation: Ethically navigating the next frontier.
AB  - As the organ shortage continues to grow, the creation of social media communities
      by transplant hospitals and the public is rapidly expanding to increase the
      number of living donors. Social media communities are arranged in myriad ways and
      without standardization, raising concerns about transplant candidates' and
      potential donors' autonomy and quality of care. Social media communities magnify
      and modify extant ethical issues in deceased and living donation related to
      privacy, confidentiality, professionalism, and informed consent, and increase the
      potential for undue influence and coercion for potential donors and transplant
      candidates. Currently, no national ethical guidelines have been developed in the
      United States regarding the use of social media to foster organ transplantation.
      We provide an ethical framework to guide transplant stakeholders in using social
      media for public and patient communication about transplantation and living
      donation, and offer recommendations for transplant clinical practice and future
      research.

PMID- 28744967
TI  - Compression therapy - cross-sectional observational survey about knowledge and
      practical treatment of specialised and non-specialised nurses and therapists.
AB  - Knowledge about methods and materials and their correct usage is the basis for
      compression therapy. This study compares knowledge and practical skills of
      participants with further training with those who had no training. This
      comparison provides information on whether further qualifications have an impact
      on knowledge and practical skills. In seminars for compression therapy, data on
      specific and non-specific expertise were acquired. A practical test determined
      the participants' skills for creating a compression bandage in a pressure value
      range of 50-60 mmHg. In total, 1338 participants with specific expertise and 138
      participants with non-specific expertise took part. Knowledge evaluation showed
      that 7.9% of the specific expertise group had knowledge regarding padding, 10%
      regarding multi-component systems and 13.6% regarding ulcer stocking systems. In
      the practical test, 12.3% of all participants achieved the target range. The
      majority of users in both groups is not familiar with the different compression
      materials or their appropriate usage. In the non-specific expertise group,
      knowledge concerning up-to-date materials and methods is one-third lower. The
      practical test showed major deficits on both sides. Appropriate exercises, for
      example, with pressure-measuring devices, should be mandatory for all
      professional groups who perform compression bandaging.

PMID- 28744968
TI  - Benchmark problems for numerical treatment of backflow at open boundaries.
AB  - In computational fluid dynamics, incoming velocity at open boundaries, or
      backflow, often yields unphysical instabilities already for moderate Reynolds
      numbers. Several treatments to overcome these backflow instabilities have been
      proposed in the literature. However, these approaches have not yet been compared
      in detail in terms of accuracy in different physiological regimes, in particular
      because of the difficulty to generate stable reference solutions apart from
      analytical forms. In this work, we present a set of benchmark problems in order
      to compare different methods in different backflow regimes (with a full reversal
      flow and with propagating vortices after a stenosis). The examples are
      implemented in FreeFem++, and the source code is openly available, making them a
      solid basis for future method developments.

PMID- 28744969
TI  - Abnormal functional activation and maturation of ventromedial prefrontal cortex
      and cerebellum during temporal discounting in autism spectrum disorder.
AB  - People with autism spectrum disorder (ASD) have poor decision-making and temporal
      foresight. This may adversely impact on their everyday life, mental health, and
      productivity. However, the neural substrates underlying poor choice behavior in
      people with ASD, or its' neurofunctional development from childhood to adulthood,
      are unknown. Despite evidence of atypical structural brain development in ASD,
      investigation of functional brain maturation in people with ASD is lacking. This
      cross-sectional developmental fMRI study investigated the neural substrates
      underlying performance on a temporal discounting (TD) task in 38 healthy (11-35
      years old) male adolescents and adults with ASD and 40 age, sex, and IQ-matched
      typically developing healthy controls. Most importantly, we assessed group
      differences in the neurofunctional maturation of TD across childhood and
      adulthood. Males with ASD had significantly poorer task performance and
      significantly lower brain activation in typical regions that mediate TD for
      delayed choices, in predominantly right hemispheric regions of
      ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex,
      striatolimbic regions, and cerebellum. Importantly, differential activation in
      ventromedial frontal cortex and cerebellum was associated with abnormal
      functional brain maturation; controls, in contrast to people with ASD, showed
      progressively increasing activation with increasing age in these regions; which
      furthermore was associated with performance measures and clinical ASD measures
      (stereotyped/restricted interests). Findings provide first cross-sectional
      evidence that reduced activation of TD mediating brain regions in people with ASD
      during TD is associated with abnormal functional brain development in these
      regions between childhood and adulthood, and this is related to poor task
      performance and clinical measures of ASD. Hum Brain Mapp 38:5343-5355, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28744970
TI  - Evaluation of a professional development training programme for mental health
      clinicians specializing in early psychosis.
AB  - The Early Psychosis Prevention and Intervention Centre Statewide Services (ESW)
      team provides training for multidisciplinary clinicians that specialise in early
      psychosis across the State of Victoria, Australia. The aim of this paper is to
      describe the 4-phase approach utilised by ESW to prepare for and deliver
      workshops, to report on participants' ratings of the ESW workshops, and to make
      recommendations for other trainers of early psychosis clinicians. Between March
      2009 and September 2014, ESW provided 85 training workshops that had a strong
      focus on evidence-based approaches and international guidelines, and utilized
      clinical examples of early psychosis interventions. At the conclusion of each
      workshop, participants were asked to complete a questionnaire that comprised
      qualitative and quantitative elements. These assessed perceived trainer
      knowledge, learning, interactivity and specific topic feedback. The focus of this
      paper will be on describing the quantitative data resulting from these
      questionnaires. A total of 1708 clinicians provided feedback on the 85 workshops.
      There was a high level of compliance, with 83.0% of workshop participants
      completing the questionnaires. Feedback was positive across all areas, with the 2
      areas that were most highly endorsed being that presenters "appeared to know
      their subject matter well" (endorsed by 98.4% of participants) and that "topics
      were explained well" (endorsed by 96.8% of participants). Training for early
      psychosis clinicians that focusses on core clinical topics, is well planned,
      incorporates feedback from previous training, and is based on adult learning
      principles, is likely to be effective and well received by early psychosis
      clinicians.

PMID- 28744971
TI  - Predicted factors for older Taiwanese to be healthy octogenarians: Results of an
      18-year national cohort study.
AB  - AIM: To identify factors that predict the 62-69 years old Taiwanese to be healthy
      octogenarians. METHODS: We analyzed the 1989 (baseline), and 2003 and 2007 (end
      point) datasets of the Taiwan Longitudinal Survey on Aging, a national cohort
      study. A total of 1977 participants aged 62-69 years at baseline were tracked for
      14-18 years. The outcome measure was "being healthy octogenarians", defined as
      participants who were aged >=80 years, free from activities of daily living
      dependency, depressive symptoms or cognitive impairment, and able to provide
      social support. A logistic regression model was used to identify the predictors.
      RESULTS: The results showed that higher educational level, conjugal living,
      absence of smoking or betel quid chewing, moderate alcohol drinking, routine
      physical activity, more leisure activities, no hypertension, no diabetes,
      sleeping well and satisfied with economic condition were the positive predictors
      for becoming a healthy octogenarian. CONCLUSIONS: Using a multidimensional
      criterion, the present study identified a list of factors in predicting older
      Taiwanese becoming healthy octogenarians. The findings highlight the need to
      identify potential factors for various populations. Many of the predictors are
      modifiable factors. The present results would be valuable for planning effective
      health promotion strategies to achieve healthy aging for older adults. Geriatr
      Gerontol Int 2017; 17: 2579-2585.

PMID- 28744972
TI  - Aggregating behaviour, social interactions and possible spawning in the deep
      water fish Coryphaenoides rupestris.
AB  - A dense aggregation of the roundnose grenadier Coryphaenoides rupestris was
      observed with a towed camera at a depth of 1500 m in the Rockall Trough during
      September. The density of fish was 100 times greater than other sites. Within the
      aggregation the fish showed directional alignment, rapid swimming actions, mid
      water swimming and social interactions similar to those associated with spawning
      in other Gadiformes.

PMID- 28744973
TI  - Addressing Chirality in the Structure and Synthesis of [18 F]5-Fluoroaminosuberic
      Acid ([18 F]FASu).
AB  - An increasing number of positron emission tomography (PET) radiotracers are being
      developed that are modelled on various amino acids to better understand disease
      in a manner that is complementary to traditional glycolysis-targeting [18 F]
      fluorodeoxyglucose. Since chiral centers are ubiquitous in amino acids,
      generating an optically pure radiolabeled amino acid is important for patient
      dose, image quality and understanding the physiology behaviour. Past studies on
      the radiosynthesis of amino acid radiotracers seldom address the impact of
      reaction conditions on their chirality. The amino acid PET tracer, [18 F]5
      fluoroaminosuberic acid ([18 F]FASu), has two chiral centers at the 2- and 5
      positions and is being developed as a specific tracer for the cystine transporter
      (system xC- ), a biomarker for oxidative stress. Herein we report a method for
      synthesizing pure 2S,5R/S-FASu. We have resolved the 5-position configuration by
      applying Mosher's method combined with 2D NMR, which has enabled the synthesis of
      18 FASu with fully known configuration. Our study serves as an example of a
      systematic method to identify and characterize amino acid tracers with chiral
      centers.

PMID- 28744975
TI  - Factors related to teamwork performance and stress of operating room nurses.
AB  - AIM: To evaluate operating room nurses' perception of teamwork performance and
      their level of mental stress and to identify related factors. BACKGROUND: Little
      is known about the factors affecting teamwork and the mental stress of surgical
      nurses, although the performance of the surgical team is essential for patient
      safety. METHODS: The questionnaire survey for operation room nurses consisted of
      simple questions about teamwork performance and mental stress. Multivariate
      analyses were used to identify factors causing a sense of teamwork performance or
      mental stress. RESULTS: A large number of surgical nurses had a sense of teamwork
      performance, but 30-40% of operation room nurses were mentally stressed during
      surgery. Neither the patient nor the operation factors were related to the sense
      of teamwork performance in both types of nurses. Among scrub nurses, endoscopic
      and abdominal surgery, body mass index, blood loss and the American Society of
      Anesthesiologists physical status class were related to their mental stress.
      Conversely, circulating nurses were stressed about teamwork performance.
      CONCLUSIONS: The factors related to teamwork performance and mental stress during
      surgery differed between scrub and circulating nurses. IMPLICATIONS FOR NURSING
      MANAGEMENT: Increased support for operation room nurses is necessary. The
      increased support leads to safer surgical procedures and better patient outcomes.

PMID- 28744974
TI  - Obestatin regulates cardiovascular function and promotes cardioprotection through
      the nitric oxide pathway.
AB  - Patients with ischaemic heart disease or chronic heart failure show altered
      levels of obestatin, suggesting a role for this peptide in human heart function.
      We have previously demonstrated that GH secretagogues and the ghrelin gene
      derived peptides, including obestatin, exert cardiovascular effects by modulating
      cardiac inotropism and vascular tone, and reducing cell death and contractile
      dysfunction in hearts subjected to ischaemia/reperfusion (I/R), through the
      Akt/nitric oxide (NO) pathway. However, the mechanisms underlying the cardiac
      actions of obestatin remain largely unknown. Thus, we suggested that obestatin
      induced activation of PI3K/Akt/NO and PKG signalling is implicated in protection
      of the myocardium when challenged by adrenergic, endothelinergic or I/R stress.
      We show that obestatin exerts an inhibitory tone on the performance of rat
      papillary muscle in both basal conditions and under beta-adrenergic
      overstimulation, through endothelial-dependent NO/cGMP/PKG signalling. This
      pathway was also involved in the vasodilator effect of the peptide, used both
      alone and under stress induced by endothelin-1. Moreover, when infused during
      early reperfusion, obestatin reduced infarct size in isolated I/R rat hearts,
      through an NO/PKG pathway, comprising ROS/PKC signalling, and converging on
      mitochondrial ATP-sensitive potassium [mitoK(ATP)] channels. Overall, our results
      suggest that obestatin regulates cardiovascular function in stress conditions and
      induces cardioprotection by mechanisms dependent on activation of an NO/soluble
      guanylate cyclase (sGC)/PKG pathway. In fact, obestatin counteracts exaggerated
      beta-adrenergic and endothelin-1 activity, relevant factors in heart failure,
      suggesting multiple positive effects of the peptide, including the lowering of
      cardiac afterload, thus representing a potential candidate in pharmacological
      post-conditioning.

PMID- 28744976
TI  - Patient experiences of adjusting to life in the first 2 years after bariatric
      surgery: a qualitative study.
AB  - There is currently little research into the experiences of those who have
      undergone bariatric surgery, or how surgery affects their lives and social
      interactions. Adopting a constructivist grounded theory methodological approach
      with a constant comparative analytical framework, semi-structured interviews were
      carried out with 18 participants (11 female, 7 male) who had undergone permanent
      bariatric surgical procedures 5-24 months prior to interview. Findings revealed
      that participants regarded social encounters after bariatric surgery as
      underpinned by risk. Their attitudes towards social situations guided their
      social interaction with others. Three profiles of attitudes towards risk were
      constructed: Risk Accepters, Risk Contenders and Risk Challengers. Profiles were
      based on participant-reported narratives of their experiences in the first two
      years after surgery. The social complexities which occurred as a consequence of
      bariatric surgery required adjustments to patients' lives. Participants reported
      that social aspects of bariatric surgery did not appear to be widely understood
      by those who have not undergone bariatric surgery. The three risk attitude
      profiles that emerged from our data offer an understanding of how patients adjust
      to life after surgery and can be used reflexively by healthcare professionals to
      support both patients pre- and post-operatively.

PMID- 28744977
TI  - Supraventricular premature beats and risk of new-onset atrial fibrillation in
      coronary artery disease.
AB  - INTRODUCTION: The significance of premature atrial contraction (PAC) count and
      supraventricular runs (SVR) for the risk of development of new-onset atrial
      fibrillation (AF) in patients with coronary artery disease (CAD) is not well
      established. METHODS: The Innovation to Reduce Cardiovascular Complications of
      Diabetes at the Intersection (ARTEMIS) study cohort consisted of 1,946 patients
      with CAD who underwent clinical and echocardiographic examinations, 24-hour
      ambulatory ECG monitoring, and laboratory tests. After excluding patients who
      were not in sinus rhythm at baseline or were lost from the follow-up, the present
      study included 1,710 patients. SVR was defined as at least four PACs in a row
      with a duration <30 seconds. RESULTS: During a follow-up for an average 5.6 +/-
      1.5 years, new-onset AF was identified in 143 (8.4%) patients. In the univariate
      analysis, both SVR and PAC count were associated with the development of new
      onset AF. When SVR and PAC count were adjusted with the established AF risk
      markers of the modified CHARGE-AF model in the Cox multivariate regression
      analysis, both parameters remained significant predictors of the occurrence of
      new-onset AF (HR = 2.529, 95 % CI = 1.763-3.628, P ? 0.001 and HR = 8.139 for
      >=1,409 PACs [the fourth quartile] vs. <=507 PACs [the first quartile], 95 % CI =
      3.967-16.696, P ? 0.001, respectively). Together these parameters improved the C
      index of the established AF risk model from 0.649 to 0.718, P < 0.001.
      CONCLUSION: Including SVR and PAC count to the established AF risk model improves
      the discrimination accuracy in predicting AF in patients with CAD.

PMID- 28744978
TI  - The role of prolactin in the suppression of Crh mRNA expression during pregnancy
      and lactation in the mouse.
AB  - Maternal stress is associated with negative health consequences for both the
      mother and her offspring. To prevent these adverse outcomes, activity of the
      hypothalamic-pituitary-adrenal (HPA) axis is attenuated during pregnancy and
      lactation. Although the mechanisms generating this adaptive change have not been
      defined fully, the anterior pituitary hormone prolactin may play a significant
      role. The present study investigated the role of prolactin in regulating the
      basal activity of the HPA axis during pregnancy and lactation in the mouse,
      focussing upon the corticotrophin-releasing hormone (CRH) neurones. Using in situ
      hybridisation, a decrease in Crh mRNA-expressing cell number in pregnant (55.6+/
      9.0 cells per section) and lactating (97.4+/-4.9) mice compared to virgin
      controls was characterised (186.8+/-18.7, P<.01 Tukey-Kramer test; n=6-7 per
      group). Removal of the pups (24 hours) and thus the associated suckling-induced
      prolactin secretion, restored CRH neurone number (180.1+/-19.7). To specifically
      test the role of prolactin in suppressing Crh mRNA expression in lactation,
      prolactin levels were selectively manipulated in lactating mice. Lactating mice
      were treated with ovine prolactin (1500 MUg day-1 , osmotic minipump, s.c.; n=7)
      or vehicle (n=6) for 24 hours following pup removal. This was sufficient to
      suppress Crh mRNA expression from 108.0+/-13.5 to 53.7+/-16.7 cells per section
      (P<.05 Student's t-test). Additional cohorts of lactating mice were treated with
      bromocriptine (300 MUg over 24 hours, s.c.; n=7) or vehicle (n=5) to suppress
      endogenous prolactin secretion; however, no change in Crh mRNA expression was
      detected. Thus, although prolactin was sufficient to suppress Crh mRNA expression
      in the paraventricular nucleus, it does not appear to be required for the ongoing
      regulation of the CRH neurones in lactation.

PMID- 28744979
TI  - Development and validation of a subcritical 1,1,1,2-tetrafluoroethane extraction
      technique: Gas chromatography-mass spectrometry method for the simultaneous
      determination of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and
      polybrominated biphenyl ethers in aquatic products.
AB  - A simple, rapid, and green method was developed for the simultaneous analysis of
      polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and polybrominated
      biphenyl ethers in aquatic products using subcritical 1,1,1,2-tetrafluoroethane
      extraction coupled with gas chromatography and mass spectrometry. Effects of the
      extraction temperature, pressure, and cosolvent volume on the extraction
      efficiency were investigated by extracting spiked oyster samples. The results
      show that the maximum extraction efficiency was obtained at 40 degrees C, 12 MPa,
      and a cosolvent (dichloromethane) volume of 5.0 mL. Under these conditions, the
      calibration curves had good linearity with square of the correlation larger than
      0.998 in the concentration range of 5-800 ng/mL; limit of detection and limit of
      quantitation were 0.16-2.83 and 0.55-9.43 ng/g, respectively. At spiked levels of
      10, 30, and 50 ng/g, the average recoveries were 70.4-80.4% for polycyclic
      aromatic hydrocarbons, 74.0-83.6% for polychlorinated biphenyls, and 66.9-78.0%
      for polybrominated biphenyl ethers, with average relative standard deviations of
      less than 16.3%. The established method has no significant differences in
      recovery compared to traditional methods and is suitable for the analysis of real
      samples.

PMID- 28744980
TI  - Building a comprehensive team for the longitudinal care of single ventricle heart
      defects: Building blocks and initial results.
AB  - INTRODUCTION: With increasing survival of children with HLHS and other single
      ventricle lesions, the complexity of medical care for these patients is
      substantial. Establishing and adhering to best practice models may improve
      outcome, but requires careful coordination and monitoring. METHODS: In 2013 our
      Heart Center began a process to build a comprehensive Single Ventricle Team
      designed to target these difficult issues. RESULTS: Comprehensive Single
      Ventricle Team in 2014 was begun, to standardize care for children with single
      ventricle heart defects from diagnosis to adulthood within our institution. The
      team is a multidisciplinary group of providers committed to improving outcomes
      and quality of life for children with single ventricle heart defects, all
      functioning within the medical home of our heart center. Standards of care were
      developed and implemented in five target areas to standardize medical management
      and patient and family support. Under the team 100 patients have been cared for.
      Since 2014 a decrease in interstage mortality for HLHS were seen. Using a team
      approach and the tools of Quality Improvement they have been successful in
      reaching high protocol compliance for each of these areas. CONCLUSIONS: This
      article describes the process of building a successful Single Ventricle team, our
      initial results, and lessons learned. Additional study is ongoing to demonstrate
      the effects of these interventions on patient outcomes.

PMID- 28744981
TI  - The concordance between self-reported medication use and pharmacy records in
      pregnant women.
AB  - PURPOSE: Several studies have been conducted to assess determinants affecting the
      performance or accuracy of self-reports. These studies are often not focused on
      pregnant women, or medical records were used as a data source where it is unclear
      if medications have been dispensed. Therefore, our objective was to evaluate the
      concordance between self-reported medication data and pharmacy records among
      pregnant women and its determinants. METHODS: We conducted a population-based
      cohort study within the Generation R study, in 2637 pregnant women. The
      concordance between self-reported medication data and pharmacy records was
      calculated for different therapeutic classes using Yule's Y. We evaluated a
      number of variables as determinant of discordance between both sources through
      univariate and multivariate logistic regression analysis. RESULTS: The
      concordance between self-reports and pharmacy records was moderate to good for
      medications used for chronic conditions, such as selective serotonin reuptake
      inhibitors or anti-asthmatic medications (0.88 and 0.68, respectively).
      Medications that are used occasionally, such as antibiotics, had a lower
      concordance (0.51). Women with a Turkish or other non-Western background were
      more likely to demonstrate discordance between pharmacy records and self-reported
      data compared with women with a Dutch background (Turkish: odds ratio, 1.63; 95%
      confidence interval, 1.16-2.29; other non-Western: odds ratio, 1.33; 95%
      confidence interval, 1.03-1.71). CONCLUSIONS: Further research is needed to
      assess how the cultural or ethnic differences may affect the concordance or
      discordance between both medication sources. The results of this study showed
      that the use of multiple sources is needed to have a good estimation of the
      medication use during pregnancy.

PMID- 28744982
TI  - mcp, aer, cheB, and cheV contribute to the regulation of Vibrio alginolyticus (ND
      01) adhesion under gradients of environmental factors.
AB  - Adhesion is a key virulence factor of pathogens and can be affected by the
      environment. Our previously research with RNA-seq indicated that mcp, aer, cheB,
      and cheV might play roles in the regulation of adhesion in Vibrio alginolyticus
      (ND-01). In order to determine whether and how environmental factors affect
      adhesion through these genes, gene silencing was performed followed by
      quantitative real-time PCR (qRT-PCR), RNAi, transmission electron microscopy, and
      adhesion, capillary, and motility assays to verify how these genes influence
      adhesion. Silencing these genes led to deficiencies in adhesion, chemotaxis,
      flagellar assembly, and motility. The expression levels of cheA, cheW, and cheY,
      which are important genes closely related to the functions of mcp, aer, cheV, and
      cheB, were significantly downregulated in all of the RNAi groups. The expression
      of mcp, aer, cheV, and cheB under different gradients of temperature, pH, and
      salinity and after starvation for various durations was also detected, which
      showed that these genes were sensitive to certain environmental stresses,
      particularly pH and starvation. Our results indicated that mcp, aer, cheB, and
      cheV: (1) are necessary for ND-01 adhesion; (2) play key roles in the bacterial
      chemotaxis pathway by controlling the expression of downstream genes; (3) might
      affect adhesion by impacting motility, though motility is not the only route
      through which adhesion is affected; and (4) contribute to the regulation of ND-01
      adhesion in natural environments with different temperatures, pH levels, and
      salinities as well as after various starvation periods.

PMID- 28744983
TI  - An Evaluation of a Clinical Pre-Exposure Prophylaxis Education Intervention among
      Men Who Have Sex with Men.
AB  - OBJECTIVE: To evaluate the impact of an HIV pre-exposure prophylaxis (PrEP)
      education intervention on PrEP awareness and use among men who have sex with men
      (MSM) attending a sexually transmitted diseases (STD) clinic. DATA SOURCES/STUDY
      SETTING: Men who have sex with men STD clinic patients. STUDY DESIGN: We
      estimated a difference-in-differences linear regression model, comparing MSM
      whose first visit to the clinic was before ("control") or after ("treatment")
      intervention implementation and controlling for patient. DATA
      COLLECTION/EXTRACTION: We used self-reported data on PrEP awareness and use from
      STD clinic intake forms. PRINCIPAL FINDINGS: Pre-exposure prophylaxis awareness
      between first and second clinic visits increased 27.2 percentage points (pp) in
      the treatment group, relative to 13.7 pp in the control group. Similarly, PrEP
      use increased 7.1 pp in the treatment group versus 2.4 pp in the control group.
      Based on adjusted estimates, the PrEP intervention increased PrEP awareness by 24
      pp (p < .01) and PrEP use by 5 pp (p = .01), increases of 63 percent and 159
      percent relative to the 6 months prior to the intervention. CONCLUSION: A brief,
      scalable STD clinic PrEP education intervention led to significantly increased
      PrEP awareness and use among MSM. Health care providers should consider
      implementing brief PrEP education interventions in sexual health care settings.

PMID- 28744985
TI  - Diffuse dermal angiomatosis mimicking inflammatory breast carcinoma.
AB  - Diffuse dermal angiomatosis (DDA) is a rare pathologically distinct subtype of
      reactive angioendotheliomatosis. In the literature, few biopsy-proven cases
      involving breast skin have been reported. We present a case of a 49-year-old
      female who presented with an indurated, erythematous, weeping, puckered and
      tender lesion with focal ulceration. Mammography demonstrated diffuse cutaneous
      and trabecular thickening concerning for inflammatory breast carcinoma. A punch
      biopsy demonstrated findings consistent with DDA. To our knowledge, this is the
      first reported case of DDA mimicking inflammatory carcinoma of the breast by
      clinical and radiologic examination.

PMID- 28744986
TI  - Complete recovery of fulminant peripartum cardiomyopathy on mechanical
      circulatory support combined with high-dose bromocriptine therapy.
AB  - Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with
      heart failure due to left ventricular systolic dysfunction towards the end of
      pregnancy or in the months following delivery, where no other cause of heart
      failure is found. We report a case of a woman with PPCM who developed a critical
      cardiogenic shock with repeated cardiopulmonary resuscitation. We show for the
      first time that mechanical circulatory support combined with high-dose
      bromocriptine therapy to suppress systemic prolactin levels may serve as an
      effective therapeutic option in patients with fulminant PPCM and cardiogenic
      shock. Myocardial cathepsin D was overexpressed in our patient underscoring a
      potential role of cathepsin D-induced cleavage of prolactin in the
      pathophysiology of PPCM.

PMID- 28744987
TI  - Is modified brief assertiveness training for nurses effective? A single-group
      study with long-term follow-up.
AB  - AIM: To evaluate the long-term effectiveness of modified brief assertiveness
      training (with cognitive techniques) for nurses. BACKGROUND: Most assertiveness
      training takes a long time to conduct; thus, briefer training is required for
      universal on-the-job training in the workplace. METHODS: In this single-group
      study, nurses received two 90-min training sessions with a 1-month interval
      between sessions. The degree of assertiveness was assessed by using the Rathus
      Assertiveness Schedule as the primary outcome, at four time points: pre- and post
      training, 3-month follow-up and 6-month follow-up. RESULTS: A total of 33 nurses
      received the training, and the mean Rathus Assertiveness Schedule score improved
      from -14.2 (SD = 16.5) pre-training to -10.5 (SD = 18.0) post-training (p < .05).
      These improvements were maintained until the 6-month follow-up. The pre-post
      effect size of 0.22 (indicating small effect) was larger than the effect sizes
      ranging from -0.56 to 0.17 (no effect) reported in previous studies that used
      brief training. CONCLUSIONS: Modified brief assertiveness training seems feasible
      and may achieve long-term favourable outcomes in improving assertiveness among
      nurses. IMPLICATIONS FOR NURSING MANAGEMENT: The ease of implementation of
      assertiveness training is important because creating an open environment for
      communication leads to improved job satisfaction, improved nursing care and
      increased patient safety.

PMID- 28744988
TI  - Adherence to evidence-based pressure injury prevention guidelines in routine
      clinical practice: a longitudinal study.
AB  - The aim of this longitudinal study was to describe adherence to evidence-based
      pressure injury (PI) prevention guidelines in routine clinical practice in
      Australian hospitals. Data were analysed from four control sites of a larger
      cluster randomised trial of a PI intervention. The sample of 799 included 220
      (27.5%) Not at risk, 344 (43.1%) At risk and 110 (13.8%) At high risk patients. A
      total of 84 (10.5%) patients developed a PI during the study: 20 (9.0% of 220) in
      the Not at risk group, 45 (13.1% of 344) in the At risk group, 15 (13.6% of 110)
      in the At high risk group and 4 (3.2% of 125) patients who did not have a risk
      assessment completed. Of all patients, 165 (20.7%) received only one PI
      prevention strategy, and 494 (61.8%) received >=2 strategies at some point during
      the study period. There was no statistical difference in the proportion of time
      the three risk groups received >=1 and >=2 strategies; on average, this was less
      than half the time they were in the study. Thus, patients were not receiving PI
      prevention strategies consistently throughout their hospital stay, although it is
      possible patients' risk changed over the study period.

PMID- 28744984
TI  - Redox homeostasis and age-related deficits in neuromuscular integrity and
      function.
AB  - Skeletal muscle is a major site of metabolic activity and is the most abundant
      tissue in the human body. Age-related muscle atrophy (sarcopenia) and weakness,
      characterized by progressive loss of lean muscle mass and function, is a major
      contributor to morbidity and has a profound effect on the quality of life of
      older people. With a continuously growing older population (estimated 2 billion
      of people aged >60 by 2050), demand for medical and social care due to functional
      deficits, associated with neuromuscular ageing, will inevitably increase. Despite
      the importance of this 'epidemic' problem, the primary biochemical and molecular
      mechanisms underlying age-related deficits in neuromuscular integrity and
      function have not been fully determined. Skeletal muscle generates reactive
      oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age
      associated oxidative damage has been suggested to be a major factor contributing
      to the initiation and progression of muscle atrophy inherent with ageing. RONS
      can modulate a variety of intracellular signal transduction processes, and
      disruption of these events over time due to altered redox control has been
      proposed as an underlying mechanism of ageing. The role of oxidants in ageing has
      been extensively examined in different model organisms that have undergone
      genetic manipulations with inconsistent findings. Transgenic and knockout rodent
      studies have provided insight into the function of RONS regulatory systems in
      neuromuscular ageing. This review summarizes almost 30 years of research in the
      field of redox homeostasis and muscle ageing, providing a detailed discussion of
      the experimental approaches that have been undertaken in murine models to examine
      the role of redox regulation in age-related muscle atrophy and weakness.

PMID- 28744989
TI  - Impact of rurality and substance use on young people at ultra high risk for
      psychosis.
AB  - BACKGROUND: Longitudinal research into early intervention for youth at ultra high
      risk (UHR) for psychosis demonstrates beneficial outcomes including increased
      treatment compliance and greater participation in education and the workforce.
      Despite known barriers for rural youth accessing mental health services, research
      comparing urban and rural UHR youth is lacking. The study included an examination
      of the impact of substance use on functioning of UHR youth. METHODS: Youth aged
      12 to 25 years were recruited from the urban area of Newcastle or the rural area
      of Orange, New South Wales, Australia, and identified as UHR by the Comprehensive
      Assessment of At Risk Mental States. Rural and urban youth were compared on
      clinical profiles, social and occupational functioning and substance use.
      RESULTS: The rural youth showed different help-seeking behaviours and had greater
      functional impairment than urban youth. Substance use was common across the
      sample of 57 youth (mean age 16.5 years, 56% female) and a history of hazardous
      substance use was associated with higher levels of depression. Rural youth (n =
      32) were more likely than urban youth to be taking antidepressants at baseline
      (44% compared with 16%). CONCLUSION: Different patterns of help seeking by rural
      UHR youth suggest a need for greater access to psychosis informed primary care
      early intervention services. Interventions should target functional decline to
      prevent adverse outcomes such as reduced community participation and
      unemployment. In addition, interventions for substance use should be a priority
      for UHR youth, who should also be screened and monitored for depressive symptoms
      and treated for depression if indicated.

PMID- 28744990
TI  - Biotechnological application of yeasts in food science: Starter cultures,
      probiotics and enzyme production.
AB  - This review is an account of experiences of two research teams (from Italy to
      Spain); the leading idea is the following: yeasts represent valuable sources in
      food science and microbiology and are a kind of food factories, because of the
      potentiality of whole cells or for their produced compounds. This review covers
      three major areas: the first section addresses the role of yeasts as starter
      cultures with a special focus on wine. The second section is an update on
      probiotic yeasts. Finally, the focus of the last section is on enzymes produced
      by yeasts, with a short description of the removal of mycotoxin.

PMID- 28744991
TI  - Utility of high density multielectrode mapping during ablation of scar-related
      ventricular tachycardia.
AB  - INTRODUCTION: Multielectrode mapping catheters (MEMC) allow the performance of
      high resolution and density maps but the utility of these catheters in
      ventricular tachycardia (VT) ablation procedures has not been yet widely
      described. We sought to evaluate the utility of a MEMC during scar-related VT
      ablation procedures. METHODS: Eighty-five consecutive scar-related VT ablation
      procedures were performed in 81 patients. In the first 26 procedures, a standard
      3.5-mm tip linear catheter was employed for endocardial/epicardial mapping
      (control group). In the following 59 procedures mapping was performed with a MEMC
      (study group). Procedural time, LV endocardial and epicardial mapping time,
      complications and ablation outcomes were compared. RESULTS: The use of the MEMC
      resulted in a significant shortening of the endocardial and epicardial mapping
      times (38 +/- 15 minutes vs. 56 +/- 24 minutes for endocardial LV mapping in the
      study and control group, respectively, P = 0.001; and 28 +/- 9 minutes vs 41 +/-
      16 minutes, for epicardial mapping, P = 0.011) as well as the total procedural
      time (177 +/- 53 minutes vs. 206 +/- 50 minutes, respectively, P = 0.02). The
      mapping density was also significantly increased in the study group (mean
      endocardial LV points: 2,143 +/- 1,419 vs. 485 +/- 174, for the study and control
      group, respectively, P < 0.0001), specially within the scar area (49.6 +/- 34
      points/cm2 vs. 8.4 +/- 4.6 points/cm2 , P < 0.001). No differences in acute and
      long-term follow-up outcomes were observed. CONCLUSIONS: High-density
      multielectrode mapping is associated with a significant reduction of procedural
      and mapping times and a significant increase of mapping density without affecting
      outcomes in patients with scar-related VT.

PMID- 28744992
TI  - The effect of 12 weeks carnosine supplementation on renal functional integrity
      and oxidative stress in pediatric patients with diabetic nephropathy: a
      randomized placebo-controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Oxidative stress is a significant contributor to the
      pathogenesis of diabetic nephropathy. Carnosine is a natural radical oxygen
      species scavenger. We investigated the effect of carnosine as an adjuvant therapy
      on urinary albumin excretion (UAE), the tubular damage marker alpha 1
      microglobulin (A1M), and oxidative stress in pediatric patients with type 1
      diabetes and nephropathy. METHODS: This randomized placebo-controlled trial
      included 90 patients with diabetic nephropathy, despite oral angiotensin
      converting enzyme inhibitors (ACE-Is), who were randomly assigned to receive
      either 12 weeks of carnosine 1 g/day (n = 45), or matching placebo (n = 45). Both
      groups were followed-up with assessment of hemoglobin A1c (HbA1c), UAE, A1M,
      total antioxidant capacity (TAC) and malondialdhyde (MDA). RESULTS: Baseline
      clinical and laboratory parameters were consistent between carnosine and placebo
      groups (P > .05). After 12 weeks, carnosine treatment resulted in significant
      decrease of HbA1c (8.2 +/- 2.1% vs 7.4 +/- 1.3%), UAE (91.7 vs 38.5 mg/g
      creatinine), A1M (16.5 +/- 6.8 mg/L vs 9.3 +/- 6.6 mg/L), MDA levels (25.5 +/-
      8.1 vs 18.2 +/- 7.7 nmol/mL) while TAC levels were increased compared with
      baseline levels (P < .001) and compared with placebo (P < .001). No adverse
      reactions due to carnosine supplementation were reported. Baseline TAC was
      inversely correlated to HbA1c (r = -0.58, P = .04) and A1M (r = -0.682, P = .015)
      among carnosine group. CONCLUSIONS: Oral supplementation with L-Carnosine for 12
      weeks resulted in a significant improvement of oxidative stress, glycemic control
      and renal function. Thus, carnosine could be a safe and effective strategy for
      treatment of pediatric patients with diabetic nephropathy.

PMID- 28744993
TI  - Clinical, radiological, and gene expression analyses in smokers and non-smokers,
      Part 2: RCT on the late healing phase of osseointegration.
AB  - BACKGROUND: The mechanisms behind the impact of smoking on osseointegration are
      not fully understood. PURPOSE: To investigate the initial clinical and molecular
      course of osseointegration of different implants in smokers and non-smokers in a
      randomized controlled trial (RCT). MATERIALS AND METHODS: Smoking (n = 16) and
      non-smoking (n = 16) patients received 3 implant types: machined, oxidized, and
      laser-modified surfaces. Baseline bone biopsies were retrieved from the implant
      sites. After 60 and 90 days, the pain score, implant stability quotient (ISQ),
      and peri-implant crevicular fluid (PICF) gene expression were analyzed.
      Furthermore, radiological and clinical assessments were made at 90 days. RESULTS:
      At 90 days, no pain was reported, irrespective of smoking habit. A higher ISQ was
      found in smokers compared with non-smokers. Marginal bone loss (MBL) was greater
      in smokers than in non-smokers. The comparison of implant surfaces revealed
      greater MBL exclusively at the machined implants in smokers. At 90 days in
      smokers, the PICF around machined implants revealed a higher expression of the
      proinflammatory cytokine, interleukin-6 (IL-6), and a lower expression of the
      osteogenic gene, osteocalcin (OC), compared with the PICF around modified
      implants. Furthermore, OC expression was lower at machined implants in smokers
      compared with machined implants in non-smokers. After adjustment for age and
      implant location (maxilla/mandible), multivariate regression revealed the
      following predictors of MBL: smoking, bleeding on probing at 90 days, hypoxia
      inducible factor 1 alpha (HIF-1alpha) expression at baseline and IL-6 expression
      in PICF at 90 days. CONCLUSIONS: During the early phase of osseointegration, non
      smokers and smokers present a similar, high implant survival. In contrast,
      smokers present a greater MBL, particularly at machined implants. HIF-1alpha
      baseline expression in the recipient bone and IL-6 expression in PICF cells are
      important molecular determinants for MBL after 90 days. It is concluded that
      smoking has an early effect on osseointegration, which is dependent on the
      implant surface properties and the local host response.

PMID- 28744994
TI  - Socially Desirable Responding and College Students with Dyslexia: Implications
      for the Assessment of Anxiety and Depression.
AB  - We investigated self-reported depressive and anxiety-related symptoms among
      college students with dyslexia, with emphasis on the role of socially desirable
      responding (SDR) in understanding these reports. Analyses included examination of
      differences in self-reported depressive symptoms, anxiety-related symptoms, and
      SDR. We also examined the relationships among SDR, depressive symptoms, anxiety
      related symptoms, and reading skills. Participants with dyslexia demonstrated
      significantly higher SDR than did participants without dyslexia, and higher SDR
      was significantly associated with lower self-reported depressive and anxiety
      related symptoms. Moreover, higher SDR was significantly associated with lower
      reading skills. There was no group difference on anxiety-related symptoms, but
      participants with dyslexia had higher depressive symptoms than did participants
      without dyslexia when SDR was controlled. Implications for the assessment of
      anxiety and depression among college students with dyslexia are discussed.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28744995
TI  - Idiopathic sudden sensorineural hearing loss and meniere syndrome: The role of
      cerebral venous drainage.
AB  - OBJECTIVES: To evaluate the influence of cerebral venous drainage on the
      pathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL) and Meniere
      syndrome (MD). DESIGN: Observational, prospective, cohort study. SETTING: ENT and
      Cardiology Departments (University of Bari, Policlinico Hospital, Bari, Italy).
      PARTICIPANTS: We enrolled 59 consecutive patients (32 males, mean age 53.05 +
      15.37 years): 40 ISSHL and 19 MD. MAIN OUTCOME MEASURE: All patients underwent
      physical examination, biochemical evaluation (glycemic and lipid profile, viral
      serology, C reactive protein, etc), audiometric (tonal, vocal, vestibular evoked
      myogenic potentials and auditory brainstem response test) and impedentiometric
      examination. The pure tone average (PTA) was calculated for the following
      frequencies: 250, 500, 1000, 2000, 3000, 4000, 8000. An echo-color Doppler
      evaluation of the venous cerebral veins, internal jugular (IJV) and vertebral
      veins (VV) at supine and 90 degrees  position was performed. RESULTS: No
      morphological alterations were found both in patients and controls. There were no
      signs of stenosis, blocked flow, membranes, etc. We found lower minimum, mean and
      maximum velocities in distal IJVs (P = .019; P = .013; P = .022; respectively)
      and left VVs (P = .027; P = .008; P = .001; respectively) in supine (0 degrees )
      position in both MD and ISSHL patients as compared to controls. The same was for
      orthostatic position (90 degrees ). We found negative correlations between the
      velocities in extracranial veins and PTA values: therefore, the worst the
      audiometric performance of the subjects, the lower the velocities in the venous
      cerebral drainage. CONCLUSIONS: Idiopathic sudden sensorineural hearing loss and
      Meniere syndrome patients showed altered venous flow in IJVs and VVs as compared
      to controls, independently from posture. This different behavior of venous tone
      control can influence the ear performance and may have a role in the pathogenesis
      of both diseases.

PMID- 28744996
TI  - Ion-pair switchable-hydrophilicity solvent-based homogeneous liquid-liquid
      microextraction for the determination of paraquat in environmental and biological
      samples before high-performance liquid chromatography.
AB  - An approach involving ion-pair switchable-hydrophilicity solvent-based
      homogeneous liquid-liquid microextraction coupled to high-performance liquid
      chromatography has been applied for the preconcentration and separation of
      paraquat in a real sample. A mixture of triethylamine and water was used as the
      switchable-hydrophilicity solvent. The pH was regulated using carbon dioxide;
      hence the ratio of the ionized and non-ionized form of triethylamine could
      control the optimum conditions. Sodium dodecyl sulfate was utilized as an ion
      pairing agent. The ion-associate complex formed between the cationic paraquat and
      sodium dodecyl sulfate was extracted into triethylamine. The separation of the
      two phases was carried out by the addition of sodium hydroxide, which changed the
      ionization state of triethylamine. The effects of some important parameters on
      the extraction recovery were investigated. Under the optimum conditions (500 MUL
      of the extraction solvent, 1 mg sodium dodecyl sulfate, 2.0 mL of 10 mol/L sodium
      hydroxide, and pH 4), the limit of detection and the limit of quantification were
      0.2 and 0.5 MUg/L, respectively, with preconcentration factor of 74. The
      precision (RSD, n = 10) was  <5%. The recovery of the analyte in environmental
      and biological samples was in the range of 90.0-92.3%.

PMID- 28744997
TI  - Severe depression as a neuropsychiatric side effect induced by dolutegravir.

PMID- 28744998
TI  - Science or popular media: What drives breast cancer online activity?
AB  - Google Trends is reflective of international awareness. Since its launch in 2004,
      there have been several landmark publications, international awareness campaigns,
      and mainstream-media events that involve breast cancer. The aim of this study was
      to assess the impact of landmark academic publications vs mainstream-media
      announcements in driving online breast cancer activity via Google Trends. Ten
      breast cancer-related themes or landmark publications (five academic publications
      and five media-related events) were used to compare the impact of online search
      activity. This activity was determined by retrospectively analyzing Google Trends
      data over a 12-year period (2004-2016) and calculating the relative search
      volume. Breast cancer searches showed a slight decrease in the twelve-year
      period. Since 2004, eight of top 10 Breast Cancer searches were in October. This
      coincides with breast cancer awareness month. The major five academic
      publications were all published in the New England Journal of Medicine or the
      Lancet. Interestingly, only one publication (Tailor-X trial) made the top 10
      spikes in relative search volume. Academic publications as expected generate
      lower rates of public awareness and Internet searching. However, if academic
      publications are coupled with media releases, there is considerable potential for
      achieving increased public awareness.

PMID- 28744999
TI  - When I say ... resilience.

PMID- 28745000
TI  - SYCP3 regulates strand invasion activities of RAD51 and DMC1.
AB  - The synaptonemal complex is a higher-ordered proteinaceous architecture formed
      between homologous chromosomes. SYCP3 is a major component of the lateral/axial
      elements in the synaptonemal complex and is essential for meiotic recombination.
      Previous genetic studies showed that SYCP3 functions in meiotic homologous
      recombination biased to interhomologous chromosomes, by regulating the strand
      invasion activities of the RAD51 and DMC1 recombinases. However, the mechanism by
      which SYCP3 regulates RAD51- and DMC1-mediated strand invasion remains elusive.
      In this study, we found that SYCP3 significantly suppresses the RAD51-mediated,
      but not the DMC1-mediated, strand invasion reaction by competing with HOP2-MND1,
      which is an activator for both RAD51 and DMC1. A SYCP3 mutant with defective
      RAD51 binding does not inhibit the RAD51-mediated homologous recombination in
      human cells. Therefore, SYCP3 may promote the DMC1-driven homologous
      recombination by attenuating the RAD51 activity during meiosis.

PMID- 28745001
TI  - Investigation of the interaction of aurantio-obtusin with human serum albumin by
      spectroscopic and molecular docking methods.
AB  - The interaction between human serum albumin (HSA) and aurantio-obtusin was
      investigated by spectroscopic techniques combined with molecular docking. The
      Stern-Volmer quenching constants (KSV ) decreased from 8.56 * 105  M-1 to 5.13 *
      105  M-1 with a rise in temperatures from 289 to 310 K, indicating that aurantio
      obtusin produced a static quenching of the intrinsic fluorescence of HSA. Time
      resolved fluorescence studies proved again that the static quenching mechanism
      was involved in the interaction. The sign and magnitude of the enthalpy change as
      well as the entropy change suggested involvement of hydrogen bonding and
      hydrophobic interaction in aurantio-obtusin-HSA complex formation. Aurantio
      obtusin binding to HSA produced significant alterations in secondary structures
      of HSA, as revealed from the time-resolved fluorescence, Fourier transform
      infrared (FT-IR) spectroscopy, three-dimensional (3D) fluorescence and circular
      dichroism (CD) spectral results. Molecular docking study and site marker
      competitive experiment confirmed aurantio-obtusin bound to HSA at site I
      (subdomain IIA).

PMID- 28745002
TI  - Dimensional changes of the maxillary sinus following tooth extraction in the
      posterior maxilla with and without socket preservation.
AB  - BACKGROUND: Sinus pneumatization is commonly observed following tooth extraction
      in the posterior maxilla, however, the role of this pneumatization in the overall
      changes in the vertical bone height is not clear. PURPOSE: To compare dimensional
      changes in the alveolar ridge and corresponding maxillary sinus following tooth
      extraction, with or without socket preservation. MATERIALS AND METHODS: 42
      patients underwent tooth extraction (control group) and 21 patients underwent
      tooth extraction with socket preservation using DBBM (study group). Panoramic
      radiographs, prior to and approximately 1 year post extractions were superimposed
      and matched using a fixed reference unit. The following measurements were
      performed in the midline of the tooth site: distance of the bone crest to the
      sinus floor; distance of the sinus floor to the sinus roof and the sagittal
      circumference of the maxillary. RESULTS: The mean change in the distance from the
      sinus floor to the sinus roof pre and post operatively was 0.30 mm (+/-0.10 SE)
      in the study group and 1.30 mm (+/-0.27 SE) in the control group (P = .0221). The
      mean change in the distance from the bone crest to the sinus floor was 0.32 mm
      (+/-0.09 SE) in the study group and 1.26 mm (+/-0.28 SE) in the control group (P
      = .0019), and the mean change in the sinus sagittal circumference was 37.34 mm
      (+/-6.10 SE) and 125.95 mm (+/-15.60 SE), respectively (P = .0001). CONCLUSIONS:
      Ridge preservation using bovine derived xenograft might reduce sinus
      pneumatization along with minimizing crestal bone resorption.

PMID- 28745003
TI  - An evolutionary perspective on the systems of adaptive immunity.
AB  - We propose an evolutionary perspective to classify and characterize the diverse
      systems of adaptive immunity that have been discovered across all major domains
      of life. We put forward a new function-based classification according to the way
      information is acquired by the immune systems: Darwinian immunity (currently
      known from, but not necessarily limited to, vertebrates) relies on the Darwinian
      process of clonal selection to 'learn' by cumulative trial-and-error feedback;
      Lamarckian immunity uses templated targeting (guided adaptation) to internalize
      heritable information on potential threats; finally, shotgun immunity operates
      through somatic mechanisms of variable targeting without feedback. We argue that
      the origin of Darwinian (but not Lamarckian or shotgun) immunity represents a
      radical innovation in the evolution of individuality and complexity, and propose
      to add it to the list of major evolutionary transitions. While transitions to
      higher-level units entail the suppression of selection at lower levels, Darwinian
      immunity re-opens cell-level selection within the multicellular organism, under
      the control of mechanisms that direct, rather than suppress, cell-level evolution
      for the benefit of the individual. From a conceptual point of view, the origin of
      Darwinian immunity can be regarded as the most radical transition in the history
      of life, in which evolution by natural selection has literally re-invented
      itself. Furthermore, the combination of clonal selection and somatic receptor
      diversity enabled a transition from limited to practically unlimited capacity to
      store information about the antigenic environment. The origin of Darwinian
      immunity therefore comprises both a transition in individuality and the emergence
      of a new information system - the two hallmarks of major evolutionary
      transitions. Finally, we present an evolutionary scenario for the origin of
      Darwinian immunity in vertebrates. We propose a revival of the concept of the
      'Big Bang' of vertebrate immunity, arguing that its origin involved a 'difficult'
      (i.e. low-probability) evolutionary transition that might have occurred only
      once, in a common ancestor of all vertebrates. In contrast to the original
      concept, we argue that the limiting innovation was not the generation of somatic
      diversity, but the regulatory circuitry needed for the safe operation of
      amplifiable immune responses with somatically acquired targeting. Regulatory
      complexity increased abruptly by genomic duplications at the root of the
      vertebrate lineage, creating a rare opportunity to establish such circuitry. We
      discuss the selection forces that might have acted at the origin of the
      transition, and in the subsequent stepwise evolution leading to the modern immune
      systems of extant vertebrates.

PMID- 28745004
TI  - Inference on network statistics by restricting to the network space: applications
      to sexual history data.
AB  - Analysis of sexual history data intended to describe sexual networks presents
      many challenges arising from the fact that most surveys collect information on
      only a very small fraction of the population of interest. In addition, partners
      are rarely identified and responses are subject to reporting biases. Typically,
      each network statistic of interest, such as mean number of sexual partners for
      men or women, is estimated independently of other network statistics. There is,
      however, a complex relationship among networks statistics; and knowledge of these
      relationships can aid in addressing concerns mentioned earlier. We develop a
      novel method that constrains a posterior predictive distribution of a collection
      of network statistics in order to leverage the relationships among network
      statistics in making inference about network properties of interest. The method
      ensures that inference on network properties is compatible with an actual
      network. Through extensive simulation studies, we also demonstrate that use of
      this method can improve estimates in settings where there is uncertainty that
      arises both from sampling and from systematic reporting bias compared with
      currently available approaches to estimation. To illustrate the method, we apply
      it to estimate network statistics using data from the Chicago Health and Social
      Life Survey. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28745005
TI  - Can a Morel-Lavallee lesion be misdiagnosed as a mass like lesion?
AB  - The Morel-Lavallee lesion (MLL) is a post-traumatic closed soft tissue degloving
      injury. Common complaints of MLL patients are a haematoma or fluid collection on
      the trunk or the lower extremity. However, the authors introduce unique cases of
      MLL that present an atypical appearance. The fluid collection was not apparent,
      and the capsule formation was not detected on preoperative image study. The main
      complaint of patients was the uncomfortable mass-like lesion that was regarded as
      a simple benign lump. The purpose of this case study is to introduce the atypical
      cases of MLL and to help other physicians make accurate diagnosis based on trial
      and error of our cases.

PMID- 28745006
TI  - Nevus of Ota (oculodermal melanocytosis) in a dog.
AB  - A 5-year-old, female, spayed Rhodesian Ridgeback presented with ocular
      melanocytosis and skin hyperpigmentation involving the distribution of the first
      and second divisions of the trigeminal nerve on the right side of the face. The
      dermatomal pattern of the hyperpigmentation was similar to nevus of Ota or
      oculodermal melanocytosis reported in humans. This condition has been associated
      with increased risk of developing secondary glaucoma and melanoma transformation
      in skin, ocular, orbital tissues, and the central nervous system. The clinical
      investigation and description of oculodermal melanocytosis (nevus of Ota) are
      presented for the first time in the dog.

PMID- 28745007
TI  - Better arthritis care: What training do community-based health professionals need
      to improve their care of people with arthritis? A Delphi study.
AB  - OBJECTIVE: The aim of the present study was to identify the competencies that non
      specialist community-based nurses and allied health professionals (AHPs) need to
      enable them to assess, care for and manage arthritis appropriately. METHODS: A
      Delphi survey with an expert panel of 43 rheumatology specialists and expert
      patients was used to identify the competencies needed by community-based nurses
      and AHPs to enable them to improve their care of people with arthritis. The
      process was informed by feedback from focus groups with arthritis patients,
      community-based nurses and AHPs. RESULTS: The core competencies in arthritis care
      needed by non-specialist community-based nurses and AHPs were identified. The key
      goals identified were to increase the understanding of arthritis and its impact
      on patients' lives, and to increase the ability to help patients to self-manage
      their condition and access support. Competencies included an understanding of the
      pathology underlying inflammatory and non-inflammatory arthritis, the ability to
      distinguish between the two and the ability to recognize early warning signs,
      with an emphasis on osteoarthritis (OA), rheumatoid arthritis, gout and septic
      arthritis. Essential competencies included the ability to engage in shared
      decision making, goal setting and signposting, to provide patients with education
      and information and to make appropriate referrals. CONCLUSIONS: Health
      professionals working in the community commonly encounter arthritis as a
      presenting problem or as a co-morbidity. The quality of care provided to people
      with inflammatory arthritis and OA in the community is currently variable. The
      present study identified the core competencies that all community-based nurses
      and AHPs should have in relation to OA and inflammatory arthritis.

PMID- 28745008
TI  - "You Cannot Collect Data Using Your Own Resources And Put It On Open Access":
      Perspectives From Africa About Public Health Data-Sharing.
AB  - Data-sharing is a desired default in the field of public health and a source of
      much ethical deliberation. Sharing data potentially contributes the largest, most
      efficient source of scientific data, but is fraught with contextual challenges
      which make stakeholders, particularly those in under-resourced contexts hesitant
      or slow to share. Relatively little empirical research has engaged stakeholders
      in discussing the issue. This study sought to explore relevant experiences,
      contextual, and subjective explanations around the topic to provide a rich and
      detailed presentation of what it means to different stakeholders and contexts to
      share data and how that can guide practice and ethical guidance. A qualitative
      design involving interviews was undertaken with professionals working in public
      health institutions endowed with data (HDSS), ethics committees, and advisory
      agencies which help shape health research in Africa. A descriptive form of
      thematic analysis was used to summarize results into six key themes: (1) The role
      of HDSSs in research using public health data and data-sharing; (2) Ownership and
      funding are critical factors influencing data-sharing; (3) Other factors
      discourage data-sharing; (4) Promoting and sustaining data-sharing; (5) Ethical
      guidance structures; and (6) Establishing effective guidance. The themes reveal
      factors regarding the willingness or not to share and an intricate ethical system
      that current discourse could reflect. Many of the concerns resonate with the
      literature, but a whole other gamut of people and process issues; commitments,
      investments, careers, and the right ethical guidance are needed to realize a
      sustainable goal of reaching 'share' as a default.

PMID- 28745009
TI  - Perfluoroalkylated Calix[4]pyrroles: Fluoride Ion Extraction from an Aqueous
      Medium.
AB  - Octaalkenyl calix[4]pyrrole ((CH2 =CH(CH2 )2 )8 C4P) is highly useful for the
      postfunctionalization of different calix[4]pyrroles with desired functionalities.
      Functionalization with perfluoroalkyl chains [CF3 (CF2 )n ; Rfn ] gave
      perfluoroalkyl calix[4]pyrroles (Rfn (CH2 )4 )8 C4P; n=6, 8), having >60 %
      fluorine content, which created a hydrophobic environment inside the
      calix[4]pyrrole cavity and recognized fluoride and chloride ions in solution as
      well as in the solid state. The fluoride ion is extracted efficiently from
      aqueous CsF and TBAF solutions by using (Rf6 (CH2 )4 )8 C4P, as droplets. The
      fluorinated chain generated a hydrophobic environment which broke the hydration
      shell associated with the anion and separated out fluoride ions as droplets from
      aqueous medium. Furthermore, the fluoride ions competitively replaced chloride
      ions from the (Rf6 (CH2 )4 )8 C4P cavity.

PMID- 28745010
TI  - The detrimental impact of extracellular bacterial proteases on wound healing.
AB  - In addition to clinical signs of infection (e.g. inflammation, purulence and
      pain), a microbial count of >=105 colony-forming units/g has historically been
      used to define wound infection. However, it is increasingly recognised that,
      rather than a high bioburden level alone being detrimental to wound healing, it
      is the virulence of the invading microorganism and the host's immune status that
      can affect clinical outcomes. Bacteria, such as Pseudomonas aeruginosa,
      Staphylococcus aureus and Staphylococcus epidermidis, have developed a range of
      virulence factors to help them overcome host defences and proliferate within the
      underlying soft tissue. More specifically, bacterial proteases are one such
      virulence factor that has been implicated in promoting the invasion and
      destruction of the host tissue. Because of the complexities of microorganisms,
      the proteases can negatively impact the wound environment, leading to delayed
      wound healing. The aim of the present paper is to describe various extracellular
      bacterial proteases; review the impact they have on the wound environment, the
      host immune response and biofilms; and discuss potential wound management
      strategies against them. The evidence discussed suggests that proteases may play
      a profound role in wound infections, contribute to the development of an
      inflammatory response and impede wound healing.

PMID- 28745011
TI  - Enhancing prevention and intervention for youth concurrent mental health and
      substance use disorders: The Research and Action for Teens study.
AB  - BACKGROUND: Concurrent mental health and substance use disorders among youth are
      associated with functional impairment in developmentally salient domains, yet
      research on prevention and intervention for this vulnerable population is sparse.
      This paper describes the rationale and design of the Research and Action for
      Teens study, an initiative designed to strengthen the evidence base for
      prevention, screening, treatment and service delivery for youth concurrent mental
      health and substance use concerns. METHODS: Four sub-studies were developed: (1)
      a cohort study examining the emergence of mental health and substance use
      concerns from early to mid-adolescence; (2) a screening and diagnosis study
      validating screening tools with a diagnostic interview; (3) a treatment study
      examining the feasibility and effectiveness of dialectical behaviour therapy
      skills training interventions for youth and family members; and (4) a systems
      study implementing cross-sectoral collaborative networks of youth-serving
      agencies using a common screening tool. RESULTS: Multiple stakeholders, including
      service providers from youth-serving agencies across sectors, consumer groups and
      family members participated in an initial consultation, and in the implementation
      of 4 sub-studies. CONCLUSIONS: Collaboration with community stakeholders across
      sectors and disciplines throughout the research process is challenging but
      feasible, and is important for the production of applicable knowledge across the
      continuum of care.

PMID- 28745012
TI  - Validation of the "early detection Primary Care Checklist" in an Italian
      community help-seeking sample: The "checklist per la Valutazione dell'Esordio
      Psicotico".
AB  - BACKGROUND: To establish the concordant validity of the "Checklist per la
      Valutazione dell'Esordio Psicotico" (CVEP) in an Italian help-seeking population.
      The CVEP is the Italian adaptation of the "early detection Primary Care
      Checklist," a 20-item tool specifically designed to assist primary care
      practitioners in identifying young people in the early stages of psychosis.
      METHODS: The checklist was completed by the referring practitioners of 168 young
      people referred to the "Reggio Emilia At Risk Mental States" Project, an early
      detection infrastructure developed under the aegis of the Regional Project on
      Early Detection of Psychosis in the Reggio Emilia Department of Mental Health.
      The concordant validity of the CVEP was established by comparing screen results
      with the outcome of the "Comprehensive Assessment of At Risk Mental States"
      (CAARMS), a gold standard assessment for identifying young people who may be at
      risk of developing psychosis. RESULTS: The simple checklist as originally
      conceived had excellent sensitivity (98%), but lower specificity (58%). Using
      only a CVEP total score of 20 or above as cut-off, the tool showed a slightly
      lower sensitivity (93%) with a substantial improvement in specificity (87%).
      Simple cross-tabulations of the individual CVEP item scores against CAARMS
      outcome to identify the more discriminant item in terms of sensitivity and
      specificity were carried out. CONCLUSIONS: In comparison to other, much longer,
      screening tools, the CVEP performed well to identify young people in the early
      stages of psychosis. Therefore, the CVEP is well suited to optimize appropriate
      referrals to specialist services, building on the skills and knowledge already
      available in primary care settings.

PMID- 28745013
TI  - Moving alcohol prevention research forward-Part II: new directions grounded in
      community-based system dynamics modeling.
AB  - BACKGROUND AND AIMS: Given the complexity of factors contributing to alcohol
      misuse, appropriate epistemologies and methodologies are needed to understand and
      intervene meaningfully. We aimed to (1) provide an overview of computational
      modeling methodologies, with an emphasis on system dynamics modeling; (2) explain
      how community-based system dynamics modeling can forge new directions in alcohol
      prevention research; and (3) present a primer on how to build alcohol misuse
      simulation models using system dynamics modeling, with an emphasis on stakeholder
      involvement, data sources and model validation. Throughout, we use alcohol misuse
      among college students in the United States as a heuristic example for
      demonstrating these methodologies. METHODS: System dynamics modeling employs a
      top-down aggregate approach to understanding dynamically complex problems. Its
      three foundational properties-stocks, flows and feedbacks-capture non-linearity,
      time-delayed effects and other system characteristics. As a methodological
      choice, system dynamics modeling is amenable to participatory approaches; in
      particular, community-based system dynamics modeling has been used to build
      impactful models for addressing dynamically complex problems. RESULTS: The
      process of community-based system dynamics modeling consists of numerous stages:
      (1) creating model boundary charts, behavior-over-time-graphs and preliminary
      system dynamics models using group model-building techniques; (2) model
      formulation; (3) model calibration; (4) model testing and validation; and (5)
      model simulation using learning-laboratory techniques. CONCLUSIONS: Community
      based system dynamics modeling can provide powerful tools for policy and
      intervention decisions that can result ultimately in sustainable changes in
      research and action in alcohol misuse prevention.

PMID- 28745015
TI  - Exploring the provision of alcohol advice by clinicians to breast cancer
      patients.
AB  - Interactions between clinicians and patients along the cancer trajectory provide
      an opportunity to deliver key messages regarding drinking behaviours and long
      term health. This study aimed to explore the extent and nature of clinician
      patient discussions regarding alcohol intake and cancer outcomes in the clinical
      breast cancer setting, using a qualitative research design involving semi
      structured interviews. Purposive sampling was used to recruit 27 breast cancer
      clinicians (eight dietitians, nine breast care nurses, 10 oncologists) across
      Victoria, Australia. Interview data were analysed using descriptive statistics
      and a content analysis approach. Clinicians' knowledge of national alcohol
      recommendations was found to be inconsistent. Clinicians reported a lack of
      patient awareness of the link between alcohol and breast cancer. Current
      frameworks for assessing and advising on patient alcohol intake were felt to be
      impractical. The extent and nature of advice provided about alcohol was
      influenced by several patient and clinician factors. The provision of alcohol
      advice in the clinical breast cancer setting is not practiced systematically by
      any professional group. New approaches are needed to support patient education
      about alcohol intake and survivorship in the clinical oncology setting.

PMID- 28745014
TI  - The hidden burden of influenza: A review of the extra-pulmonary complications of
      influenza infection.
AB  - Severe influenza infection represents a leading cause of global morbidity and
      mortality. Although influenza is primarily considered a viral infection that
      results in pathology limited to the respiratory system, clinical reports suggest
      that influenza infection is frequently associated with a number of clinical
      syndromes that involve organ systems outside the respiratory tract. A
      comprehensive MEDLINE literature review of articles pertaining to extra-pulmonary
      complications of influenza infection, using organ-specific search terms, yielded
      218 articles including case reports, epidemiologic investigations, and autopsy
      studies that were reviewed to determine the clinical involvement of other organs.
      The most frequently described clinical entities were viral myocarditis and viral
      encephalitis. Recognition of these extra-pulmonary complications is critical to
      determining the true burden of influenza infection and initiating organ-specific
      supportive care.

PMID- 28745016
TI  - Associations between self-reported sleep quality and white matter in community
      dwelling older adults: A prospective cohort study.
AB  - Both sleep disturbances and decline in white matter microstructure are commonly
      observed in ageing populations, as well as in age-related psychiatric and
      neurological illnesses. A relationship between sleep and white matter
      microstructure may underlie such relationships, but few imaging studies have
      directly examined this hypothesis. In a study of 448 community-dwelling members
      of the Whitehall II Imaging Sub-Study aged between 60 and 82 years (90 female,
      mean age 69.2 +/- 5.1 years), we used the magnetic resonance imaging technique
      diffusion tensor imaging to examine the relationship between self-reported sleep
      quality and white matter microstructure. Poor sleep quality at the time of the
      diffusion tensor imaging scan was associated with reduced global fractional
      anisotropy and increased global axial diffusivity and radial diffusivity values,
      with small effect sizes. Voxel-wise analysis showed that widespread frontal
      subcortical tracts, encompassing regions previously reported as altered in
      insomnia, were affected. Radial diffusivity findings remained significant after
      additional correction for demographics, general cognition, health, and lifestyle
      measures. No significant differences in general cognitive function, executive
      function, memory, or processing speed were detected between good and poor sleep
      quality groups. The number of times participants reported poor sleep quality over
      five time-points spanning a 16-year period was not associated with white matter
      measures. In conclusion, these data demonstrate that current sleep quality is
      linked to white matter microstructure. Small effect sizes may limit the extent to
      which poor sleep is a promising modifiable factor that may maintain, or even
      improve, white matter microstructure in ageing. Hum Brain Mapp 38:5465-5473,
      2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28745017
TI  - Activation of Engineered Protein Tyrosine Phosphatases with the Biarsenical
      Compound AsCy3-EDT2.
AB  - Methods for activating signaling enzymes hold significant potential for the study
      of cellular signal transduction. Here we present a strategy for engineering
      chemically activatable protein tyrosine phosphatases (actPTPs). To generate
      actPTP1B, we introduced three cysteine point mutations in the enzyme's WPD loop.
      Biarsenical compounds were screened for the capability to bind actPTP1B's WPD
      loop and increase its phosphatase activity. We identified AsCy3-EDT2 as a robust
      activator that selectively targets actPTP1B in proteomic mixtures and intact
      cells. Introduction of the corresponding mutations in T-cell PTP also generates
      an enzyme (actTCPTP) that is strongly activated by AsCy3-EDT2 . Given the
      conservation of WPD-loop structure among the classical PTPs, our results
      potentially provide the groundwork of a widely generalizable approach for
      generating actPTPs as tools for elucidating PTP signaling roles as well as
      connections between dysregulated PTP activity and human disease.

PMID- 28745018
TI  - A comparison between linguistic skills and socio-communicative abilities in
      Williams syndrome.
AB  - BACKGROUND: Individuals with Williams syndrome (WS) show a disharmonic linguistic
      profile with a clear pattern of strengths and weaknesses. Despite their sociable
      nature, atypical socio-communicative abilities and deficits in communication and
      relationship with others have been found. AIM: The aim of the present study was
      to investigate whether linguistic skills (LS) were in line with the pragmatic and
      social use of language and the cognitive development of 32 individuals with WS
      (18 boys and 14 girls) with a mean chronological age of 12.3 (+/-4.4) years. To
      examine the relationship between language and mental age (MA) at different ages,
      the issue was investigated in children and adolescents/young adults with WS.
      METHOD: Measures of LS, including lexical and morphosyntactic competences, and
      adaptive socio-communicative abilities (ASCA), pertaining to the use of language
      in daily living social context, were compared with the MA of participants. In a
      second step, participants with WS were split into two subgroups based on age, and
      the relationship between LS, ASCA and MA was studied. RESULTS: Although
      expressive and receptive LS were generally found to be in line with or better
      than would be expected for MA, specific deficits in receptive ASCA were
      documented. LS and ASCA appeared to have a different evolution during the
      different time windows considered. CONCLUSIONS: Our results underlined the
      importance of assessing linguistic abilities in the context of adaptive
      functioning, to guide educational and rehabilitative strategies for individuals
      with WS.

PMID- 28745019
TI  - Identifying cancer drug regimens in French health insurance database: An
      application in multiple myeloma patients.
AB  - PURPOSE: There is no consensus on how to handle complex drug combinations of
      cancer drugs through medico-administrative databases. Our objective was to
      develop an algorithm for identifying the nature and patterns of treatment lines
      in a cohort of newly treated multiple myeloma patients. METHODS: A cohort of
      multiple myeloma patients starting a first treatment line was built using both
      ambulatory and hospital data from regional data of the French national healthcare
      system database (SNIIRAM). Patients were identified from January 2011 to
      September 2013 using ICD-10 codes for multiple myeloma ('C90') within long-term
      conditions or diagnosis from hospital data. Drugs of interest for cycle
      identification included bortezomib, imids (thalidomide, lenalidomide), alkylating
      drugs (cyclophosphamide, melphalan, bendamustine, doxorubicin) and dexamethasone.
      An algorithm was applied to define combinations of treatment received in the
      first 6 months of treatment. RESULTS: Among the 236 patients included, 45%
      received bortezomib-melphalan-prednisone (VMP: n = 107), 22% bortezomib
      thalidomide-dexamethasone (VTD/VTD-PACE: n = 52) and 21% melphalan-prednisone
      thalidomide (MPT: n = 49). Other drug regimens consisted in melphalan-prednisone
      (MP: 7%, n = 17), lenalidomide-dexamethasone (RD) (4%, n = 9), bortezomib
      cyclophosphamide-dexamethasone (VCD: n = 1) and bortezomib-bendamustine
      dexamethasone (VBD: n = 1). Type of drug regimens and allocation by age class (+/
      65 years) were in accordance with current recommendations. CONCLUSIONS: This
      study demonstrates the feasibility of identifying complex drug regimens in onco
      haematology, using both outpatient and inpatient drug records in French health
      insurance databases.

PMID- 28745020
TI  - Distinct roles of the 7-transmembrane receptor protein Rta3 in regulating the
      asymmetric distribution of phosphatidylcholine across the plasma membrane and
      biofilm formation in Candida albicans.
AB  - Fungal pathogens such as Candida albicans exhibit several survival mechanisms to
      evade attack by antifungals and colonise host tissues. Rta3, a member of the Rta1
      like family of lipid-translocating exporters has a 7-transmembrane domain
      topology, similar to the G-protein-coupled receptors and is unique to the fungal
      kingdom. Our findings point towards a role for the plasma membrane localised Rta3
      in providing tolerance to miltefosine, an analogue of alkylphosphocholine, by
      maintaining mitochondrial energetics. Concurrent with miltefosine susceptibility,
      the rta3Delta/Delta strain displays increased inward translocation (flip) of
      fluorophore-labelled phosphatidylcholine (PC) across the plasma membrane
      attributed to enhanced PC-specific flippase activity. We also assign a novel role
      to Rta3 in the Bcr1-regulated pathway for in vivo biofilm development.
      Transcriptome analysis reveals that Rta3 regulates expression of Bcr1 target
      genes involved in cell surface properties, adhesion, and hyphal growth. We show
      that rta3Delta/Delta mutant is biofilm-defective in a rat venous catheter model
      of infection and that BCR1 overexpression rescues this defect, indicating that
      Bcr1 functions downstream of Rta3 to mediate biofilm formation in C. albicans.
      The identification of this novel Rta3-dependent regulatory network that governs
      biofilm formation and PC asymmetry across the plasma membrane will provide
      important insights into C. albicans pathogenesis.

PMID- 28745022
TI  - Characterized cantharidin distribution and related gene expression patterns in
      tissues of blister beetles, Epicauta chinensis.
AB  - Cantharidin (CTD), a terpenoid defensive toxin mainly produced by blister
      beetles, is widely known by its toxicity to both cancer cells and pests. However,
      little information is known about its biosynthesis in blister beetles. In this
      study, first we determined the CTD content in various tissues of adult blister
      beetles on different days after mating, and then detected the temporal and
      spatial expression patterns of genes related to CTD biosynthesis in Epicauta
      chinensis. Results revealed that the accessory gland is the source of the highest
      CTD production. The second highest level was in the fat body in male blister
      beetles after mating. In females, the highest CTD content was in the reproductive
      system except the ovary after mating. As revealed by messenger RNA expression
      level analysis, the highest levels of 3-hydroxy-3-methylglutary-CoA reductase
      (HMGR) and juvenile hormone epoxide hydrolase (JHEH) transcripts of E. chinensis
      were observed in the fat body in males after mating. However, the highest
      transcript level of EcHMGR was in the ovary and EcJHEH was maintained at a nearly
      similar level in females. The transcript level of methyl-farnesoate epoxide was
      significantly higher in the head and that of CYP4BM1 in the midgut in both male
      and female E. chinensis. We speculate that the fat body may play a more important
      role than other tissues on the CTD biosynthesis in male E. chinensis after
      mating. There may be multiple tissues involved in the process of CTD
      biosynthesis. These four genes probably play regulatory roles in different
      tissues in males.

PMID- 28745021
TI  - The impact of T1 versus EPI spatial normalization templates for fMRI data
      analyses.
AB  - Spatial normalization of brains to a standardized space is a widely used approach
      for group studies in functional magnetic resonance imaging (fMRI) data. Commonly
      used template-based approaches are complicated by signal dropout and distortions
      in echo planar imaging (EPI) data. The most widely used software packages
      implement two common template-based strategies: (1) affine transformation of the
      EPI data to an EPI template followed by nonlinear registration to an EPI template
      (EPInorm) and (2) affine transformation of the EPI data to the anatomic image for
      a given subject, followed by nonlinear registration of the anatomic data to an
      anatomic template, which produces a transformation that is applied to the EPI
      data (T1norm). EPI distortion correction can be used to adjust for geometric
      distortion of EPI relative to the T1 images. However, in practice, this EPI
      distortion correction step is often skipped. We compare these template-based
      strategies empirically in four large datasets. We find that the EPInorm approach
      consistently shows reduced variability across subjects, especially in the case
      when distortion correction is not applied. EPInorm also shows lower estimates for
      coregistration distances among subjects (i.e., within-dataset similarity is
      higher). Finally, the EPInorm approach shows higher T values in a task-based
      dataset. Thus, the EPInorm approach appears to amplify the power of the sample
      compared to the T1norm approach when not using distortion correction (i.e., the
      EPInorm boosts the effective sample size by 12-25%). In sum, these results argue
      for the use of EPInorm over the T1norm when no distortion correction is used. Hum
      Brain Mapp 38:5331-5342, 2017. (c) 2017 The Authors Human Brain Mapping Published
      by Wiley Periodicals, Inc.

PMID- 28745023
TI  - Is Fatty Liver a Risk Marker for Heart Failure?

PMID- 28745024
TI  - Diet Quality in Midadulthood Predicts Visceral Adiposity and Liver Fatness in
      Older Ages: The Multiethnic Cohort Study.
AB  - OBJECTIVE: The relationship of diet quality assessed by established indices (HEI
      2010, AHEI-2010, aMED, DASH) with adiposity measures was examined, especially
      visceral adipose tissue (VAT) and nonalcoholic fatty liver (NAFL). METHODS: Close
      to 2,000 participants of the Multiethnic Cohort completed validated food
      frequency questionnaires at cohort entry (1993-1996) and clinic visit (2013-2016)
      when they underwent whole-body dual-energy x-ray absorptiometry and abdominal
      magnetic resonance imaging scans. Linear regression was used to estimate mean
      values of adiposity measures by dietary index tertiles at baseline and
      standardized regression coefficients (betas ) after adjusting for total adiposity
      and other covariates. Logistic regression of VAT and NAFL on dietary indices was
      also performed. RESULTS: Higher dietary quality scores at cohort entry were
      inversely related to all adiposity measures, with the strongest associations for
      percent liver fat (betas  = -0.14 to -0.08), followed by VAT (betas  = -0.11 to 
      0.05), BMI (betas  = -0.11 to -0.06), and total body fat (betas  = -0.09 to 
      0.05). Odds ratios adjusted for total adiposity ranged between 0.57 and 0.77 for
      NAFL and between 0.41 and 0.65 for high VAT when comparing the highest versus
      lowest tertiles of diet quality. CONCLUSIONS: These longitudinal findings
      indicate that maintaining a high-quality diet during mid-to-late adulthood may
      prevent adverse metabolic consequences related to VAT and NAFL.

PMID- 28745025
TI  - Nonalcoholic Steatohepatitis is Associated with Cardiac Remodeling and
      Dysfunction.
AB  - OBJECTIVE: Preliminary data suggest that nonalcoholic fatty liver disease is
      associated with early heart failure (HF). However, whether nonalcoholic
      steatohepatitis (NASH) is directly associated with echocardiographic changes in
      cardiac structure or function remains unknown. METHODS: A retrospective cohort
      was identified of individuals (N = 65) without known heart disease, undergoing
      elective bariatric surgery with perioperative liver biopsy, and available recent
      transthoracic echocardiography (TTE). TTE measures were evaluated by NASH status
      using correlation coefficients, ANOVA, and linear regression, accounting for
      cardiometabolic factors. RESULTS: Median age was 47 years; 22% (n = 14) had NASH.
      NASH patients had increased median left atrial (LA) volume (28.6 mL/m2 vs. 24.8
      mL/m2 ; P < 0.0001) and left ventricular (LV) mass (82.6 g/m2 vs. 78.6 g/m2 ; P <
      0.0001), indexed for height. NASH was inversely correlated with indices of
      diastolic function, including septal E' (r = -0.90 [95% CI: -1.21 to -0.42]; P =
      0.020) and E:A (r = -0.31 [95% CI: -0.51 to -0.09]; P = 0.037). In adjusted
      analyses, NASH remained associated with increased LV mass index (beta1  = 7.16
      [SE: 4.95]; P = 0.001) and LA volume index (beta1  = 0.19 [SE: 0.08]; P = 0.001)
      and reduced lateral and septal E' (beta1  = -0.91, P = 0.015; beta1  = -0.89, P =
      0.047, respectively). CONCLUSIONS: In this bariatric cohort, NASH was associated
      with changes in myocardial structure and in load-dependent indices of LV
      diastolic function, suggestive of subclinical HF.

PMID- 28745026
TI  - Resistance, tolerance and environmental transmission dynamics determine host
      extinction risk in a load-dependent amphibian disease.
AB  - While disease-induced extinction is generally considered rare, a number of
      recently emerging infectious diseases with load-dependent pathology have led to
      extinction in wildlife populations. Transmission is a critical factor affecting
      disease-induced extinction, but the relative importance of transmission compared
      to load-dependent host resistance and tolerance is currently unknown. Using a
      combination of models and experiments on an amphibian species suffering
      extirpations from the fungal pathogen Batrachochytrium dendrobatidis (Bd), we
      show that while transmission from an environmental Bd reservoir increased the
      ability of Bd to invade an amphibian population and the extinction risk of that
      population, Bd-induced extinction dynamics were far more sensitive to host
      resistance and tolerance than to Bd transmission. We demonstrate that this is a
      general result for load-dependent pathogens, where non-linear resistance and
      tolerance functions can interact such that small changes in these functions lead
      to drastic changes in extinction dynamics.

PMID- 28745027
TI  - Histologic and histomorphometric assessment of sinus-floor augmentation with beta
      tricalcium phosphate alone or in combination with pure-platelet-rich plasma or
      platelet-rich fibrin: A randomized clinical trial.
AB  - BACKGROUND: The potential effects of adding pure platelet-rich plasma (P-PRP) or
      platelet-rich fibrin (PRF) to beta-tricalcium phosphate (beta-TCP) graft
      substitute on bone formation and regeneration after maxillary sinus-floor
      elevation remains unclear. PURPOSE: To compare the histologic and
      histomorphometric outcomes of maxillary sinus-floor augmentation among beta-TCP
      alone, P-PRP-mixed beta-TCP, and PRF-mixed beta-TCP. MATERIAL AND METHODS: In
      this randomized clinical trial, elevated sinus cavities were grafted with beta
      TCP (the control group), P-PRP-mixed beta-TCP (the P-PRP group), and PRF-mixed
      beta-TCP (PRF group). The sample was composed of 26 patients: 9 subjects in
      control and P-PRP groups, and 8 subjects in PRF group. After a 6-month, healing
      period, bone graft biopsies were harvested prior to implant placement, and the
      specimens were analyzed. The main outcome variables included findings of
      histologic and histomorphometric analyses of the bone graft biopsies. The data
      were analyzed by ANOVA and Tukey HSD tests. RESULTS: The mean percentages of new
      bone formations were 33.40 +/- 10.43%, 34.83 +/- 10.12%, and 32.03 +/- 6.34% in
      control, P-PRP, and PRF groups, respectively, with no significant differences (P
      > .05). Mean percentages of residual graft particle area were 30.39 +/- 10.29%,
      28.98 +/- 7.94%, and 32.66 +/- 7.46% in control, P-PRP, and PRF groups,
      respectively, with no significant differences (P > .05). The mean percentages of
      soft-tissue area were 36.21 +/- 10.59%, 36.19 +/- 13.94%, and 35.31 +/- 10.81% in
      control, P-PRP, and PRF groups, respectively, with no significant differences (P
      > .05). Mean densities of osteoblasts, osteoclasts, osteocytes, and capillary
      vessels showed insignificant difference between groups (P > .05), but
      osteoprogenitor cells were lower and inflammatory cells were higher in the PRF
      group than those in other groups (P < .01). Biopsies of P-PRP, PRF, and control
      groups showed similar composition and distribution of histologic structures.
      CONCLUSION: These findings suggested that adding P-PRP or PRF to beta-TCP graft
      substitute was not beneficial on new bone formation and regeneration, and P-PRP
      plus beta-TCP or PRF plus beta-TCP is not superior to beta-TCP alone.

PMID- 28745028
TI  - Chemical communication, sexual selection, and introgression in wall lizards.
AB  - Divergence in communication systems should influence the likelihood that
      individuals from different lineages interbreed, and consequently shape the
      direction and rate of hybridization. Here, we studied the role of chemical
      communication in hybridization, and its contribution to asymmetric and sexually
      selected introgression between two lineages of the common wall lizard (Podarcis
      muralis). Males of the two lineages differed in the chemical composition of their
      femoral secretions. Chemical profiles provided information regarding male
      secondary sexual characters, but the associations were variable and inconsistent
      between lineages. In experimental contact zones, chemical composition was weakly
      associated with male reproductive success, and did not predict the likelihood of
      hybridization. Consistent with these results, introgression of chemical profiles
      in a natural hybrid zone resembled that of neutral nuclear genetic markers
      overall, but one compound in particular (tocopherol methyl ether) matched closely
      the introgression of visual sexual characters. These results imply that
      associations among male chemical profiles, sexual characters, and reproductive
      success largely reflect transient and environmentally driven effects, and that
      genetic divergence in chemical composition is largely neutral. We therefore
      suggest that femoral secretions in wall lizards primarily provide information
      about residency and individual identity rather than function as sexual signals.

PMID- 28745029
TI  - ADAM10 and Notch1 on murine dendritic cells control the development of type 2
      immunity and IgE production.
AB  - BACKGROUND: Allergy and allergic asthma are significant health burdens in
      developed countries and are increasing in prevalence. Dendritic cells (DCs)
      initiate immune responses to common aeroallergens, and ADAM10 has been
      demonstrated to be important for the development of adaptive responses. This
      study's objective was to understand the role of ADAM10 on DCs in the development
      of allergic and anaphylactic responses. METHODS: In this study, we used mouse
      models of allergic airway inflammation (house dust mice and Alternaria alternata)
      and OVA-induced models of active anaphylaxis to determine the DC-specific
      function of ADAM10 and Notch signaling. To examine TH 1 and TH 17 immunity
      infection with Anaplasma phagocytophilum and Citrobacter rodentium respectively,
      were used. RESULTS: Mice, which have ADAM10 deleted from DCs, have dramatic
      reductions in IgE production and do not develop significant TH 2 immune
      responses. Further, ADAM10DC-/- mice are resistant to IgE-mediated anaphylaxis.
      This response is selective for TH 2 immunity as TH 1 and TH 17 immunity is
      largely unaffected. Notch1, a known ADAM10 substrate, when knocked out of DCs
      (Notch1DC-/- ) demonstrated a similar reduction in anaphylaxis and IgE. Without
      ADAM10 and Notch1 signaling, DCs were unable to make cytokines that stimulate TH
      2 cells and cytokines. Anaphylaxis and allergic lung inflammation were restored
      in ADAM10DC-/- with the overexpression of the Notch1-intracellular domain,
      confirming the role of Notch signaling. CONCLUSIONS: Targeting ADAM10 and Notch1
      on DCs represent a novel strategy for modulating TH 2 immune responses and IgE
      production.

PMID- 28745030
TI  - Cause-specific mortality and cancer morbidity in 390 male workers exposed to high
      purity talc, a six-decade follow-up.
AB  - BACKGROUND: This study updates information on mortality and cancer morbidity in a
      cohort of Norwegian talc workers. METHODS: Follow-up was extended with 24 years,
      covering 1953-2011. Comparisons were made with the general population and between
      subgroups within the cohort. RESULTS: Standardized mortality ratio for non
      malignant respiratory disease (NMRD) was 0.38 (95%CI: 0.18, 0.69) and for
      diseases of the circulatory system (CVD) 0.98 (95%CI: 0.82, 1.16). A non
      significantly increased NMRD risk was observed at high dust exposures. There were
      no deaths from pneumoconiosis. CONCLUSIONS: With the clear limitations of a small
      cohort, our results do hint at an effect of talc dust on mortality from NMRD
      other than pneumoconiosis, covered by a strong and persisting healthy worker
      effect. Also, an effect on CVD mortality, masked by a healthy worker selection
      into the cohort cannot be ruled out. Excess mortality from pneumoconiosis seen in
      other studies, may reflect exposure to quartz and, possibly, bias due to
      comparability problems.

PMID- 28745031
TI  - A tale of two tails: The importance of unstructured termini in the aggregation
      pathway of beta2-microglobulin.
AB  - The identification of intermediate states for folding and aggregation is
      important from a fundamental standpoint and for the design of novel therapeutic
      strategies targeted at conformational disorders. Protein human beta2
      microglobulin (HB2m) is classically associated with dialysis-related amyloidosis,
      but the single point mutant D76N was recently identified as the causative agent
      of a hereditary systemic amyloidosis affecting visceral organs. Here, we use D76N
      as a model system to explore the early stage of the aggregation mechanism of HB2m
      by means of an integrative approach framed on molecular simulations. Discrete
      molecular dynamics simulations of a structured-based model predict the existence
      of two intermediate states populating the folding landscape. The intermediate I1
      features an unstructured C-terminus, while I2 , which is exclusively populated by
      the mutant, exhibits two unstructured termini. Docking simulations indicate that
      I2 is the key species for aggregation at acidic and physiological pH contributing
      to rationalize the higher amyloidogenic potential of D76N relative to the wild
      type protein and the DeltaN6 variant. The analysis carried out here recapitulates
      the importance of the DE-loop in HB2m self-association at a neutral pH and
      predicts a leading role of the C-terminus and the adjacent G-strand in the
      dimerization process under acidic conditions. The identification of aggregation
      hot-spots is in line with experimental results that support the importance of
      Phe56, Asp59, Trp60, Phe62, Tyr63, and Tyr66 in HB2m amyloidogenesis. We further
      predict the involvement of new residues such as Lys94 and Trp95 in the
      aggregation process.

PMID- 28745032
TI  - Stable megadalton TOC-TIC supercomplexes as major mediators of protein import
      into chloroplasts.
AB  - Preproteins are believed to be imported into chloroplasts through membrane
      contact sites where the translocon complexes of the outer (TOC) and inner (TIC)
      envelope membranes are assembled together. However, a single TOC-TIC supercomplex
      containing preproteins undergoing active import has not yet been directly
      observed. We optimized the blue native polyacrylamide gel electrophoresis (PAGE)
      (BN-PAGE) system to detect and resolve megadalton (MD)-sized complexes. Using
      this optimized system, the outer-membrane channel Toc75 from pea chloroplasts was
      found in at least two complexes: the 880-kD TOC complex and a previously
      undetected 1-MD complex. Two-dimensional BN-PAGE immunoblots further showed that
      Toc75, Toc159, Toc34, Tic20, Tic56 and Tic110 were all located in the 880-kD to
      1.3-MD region. During active preprotein import, preproteins were transported
      mostly through the 1-MD complex and a smaller amount of preproteins was also
      detected in a complex of 1.25 MD. Antibody-shift assays showed that the 1-MD
      complex is a TOC-TIC supercomplex containing at least Toc75, Toc159, Toc34 and
      Tic110. Results from crosslinking and import with Arabidopsis chloroplasts
      suggest that the 1.25-MD complex is also a supercomplex. Our data provide direct
      evidence supporting that chloroplast preproteins are imported through TOC-TIC
      supercomplexes, and also provide the first size estimation of these
      supercomplexes. Furthermore, unlike in mitochondria where translocon
      supercomplexes are only transiently assembled during preprotein import, in
      chloroplasts at least some of the supercomplexes are preassembled stable
      structures.

PMID- 28745033
TI  - Psychometric investigation of the specific phobia of vomiting inventory: A new
      factor model.
AB  - Well-validated, standardized measures are lacking for the assessment of
      emetophobia, the specific phobia of vomiting. The Specific Phobia of Vomiting
      Inventory (SPOVI) was recently developed and shows promise as a useful measure of
      emetophobia. The goal of the present study was to further examine and investigate
      the psychometric properties of the SPOVI in a large student sample (n = 1626),
      specifically focusing on its factor structure, measurement invariance across
      gender, and convergent/divergent validity. Confirmatory factor analysis results
      provide support for a one-factor model of the SPOVI, in contrast to the
      previously proposed two-factor model. Internal consistency of the SPOVI was good
      (alpha = 0.89) and measurement invariance across gender invariance was supported.
      The SPOVI also demonstrated good psychometric properties with respect to
      convergent and divergent validity. The present study's demonstration of the
      reliability and validity of the SPOVI suggests that the instrument may be a
      valuable tool for assessing emetophobia symptoms based on its one-factor
      structure.

PMID- 28745034
TI  - Transglutaminase antibodies and celiac disease in children with type 1 diabetes
      and in their family members.
AB  - OBJECTIVES: We set out to determine the prevalence of tissue transglutaminase
      antibodies (anti-tTG) and celiac disease (CD) in children with newly diagnosed
      type 1 diabetes (T1D) and their first-degree relatives (FDR). The hypothesis was
      that the individuals with both diabetes and CD form a distinct subgroup in terms
      of human leukocyte antigen (HLA) class II genetics, islet autoantibodies, and
      clinical characteristics at diabetes diagnosis. SUBJECTS AND METHODS: This
      population-based observational study included 745 index children with T1D and
      their 2692 FDR from the Finnish Pediatric Diabetes Register. CD was ascertained
      by registers, patient records, and screening anti-tTG positive individuals for
      further testing. RESULTS: Among the index children, 4.8% had anti-tTG at diabetes
      diagnosis, and at the end of the study 3.2% had CD. Among the relatives, 2.9% had
      anti-tTG (4.8% mothers, 2.4% fathers, and 2.1% siblings), and 2.5% had CD (4.6%
      mothers, 2.1% fathers, and 1.4% siblings). Anti-tTG and CD associated with the
      HLA DR3-DQ2 haplotype. The usual female predominance of CD patients was observed
      in relatives (70%) but not among index children (46%). The index children with
      both diseases had a lower number of detectable islet autoantibodies than those
      with diabetes alone. CONCLUSIONS: The children with double diagnosis differed
      from those with diabetes alone in HLA genetics, humoral islet autoimmunity
      directed against fewer antigens, and in the lack of usual female preponderance
      among CD patients. Compared with 61% of the anti-tTG positive relatives, only 36%
      of anti-tTG positive index children developed CD implicating transient anti-tTG
      positivity at diagnosis of T1D.

PMID- 28745035
TI  - Evaluation of complication rates and vertical bone gain after guided bone
      regeneration with non-resorbable membranes versus titanium meshes and resorbable
      membranes. A randomized clinical trial.
AB  - BACKGROUND: The partial edentulous posterior mandible is often a challenge area
      that requires a bone reconstructive surgery for implants placement. PURPOSE: This
      RCT was aimed to evaluate complications rate and vertical bone gain after Guided
      Bone Regeneration (GBR) with dense non-resorbable d-PTFE titanium-reinforced
      membranes (Group A) versus titanium meshes covered by cross-linked collagen
      membranes (Group B). MATERIAL AND METHODS: 40 partially edentulous patients with
      atrophic posterior mandible, were randomly divided into two study group: 20
      patients were treated with one stage GBR by means of non-resorbable d-PTFE
      titanium-reinforced membranes (Group A); and 20 patients, by means of titanium
      mesh covered by cross-linked collagen membranes (Group B). All complications were
      recorded, distinguishing between "surgical" and "healing" and between "minor" or
      "major.". Primary implants stability and vertical bone gain were also evaluated.
      RESULTS: In the group A, surgical and healing complication rates were 5.0% and
      15.0%, respectively. In the group B, surgical and healing complication rates were
      15.8% and 21.1%, respectively. No significant differences between two study group
      were observed regarding complications rate implant stability and vertical bone
      gain. CONCLUSIONS: Both GBR approaches for the restoration of atrophic posterior
      mandible achieved similar results regarding complications, vertical bone gain and
      implant stability.

PMID- 28745036
TI  - Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for
      Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World
      Study in an Endemic Area.
AB  - Purpose: The purpose of this study was to investigate the effect of neutropenia
      during the first cycle of induction chemotherapy (IC-1) on survival in
      locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods:
      Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy
      were included. Based on nadir neutrophil afterIC-1, all patientswere categorized
      into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival
      (OS) and disease-free survival (DFS) were compared between groups and subgroups
      stratified by IC regimen. We also explored the occurrence of IC-1-induced
      myelosuppression events and the minimal value of post-treatment neutrophil-to
      lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed
      to investigate the effect of IC-1-induced neutropenia, timing of neutropenia,
      number of myelosuppression events, and high post-NLRmin on OS/DFS. Results: Grade
      1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia
      (all p < 0.05); OS/DFS were not significantly different between patients
      experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect
      on OS/DFS in patients receiving docetaxel-cisplatin-5-fluorouracil (TPF). Grade 1
      2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving
      cisplatin-5-fluorouracil (PF) (PF and docetaxel-cisplatin [TP]; all p < 0.05).
      Neutropenia, two/three myelosuppression events, and high post-NLRmin (>= 1.33)
      was most frequent on days 5-10, second and third week of IC-1, respectively.
      After adjustment for covariates, IC-1-induced neutropenia, two/three
      myelosuppression events, and post-NLRmin >= 1.33were validated as negative
      predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant
      effect. Conclusion: Occurrence of neutropenia, number of myelosuppression events,
      and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in
      LANPC.

PMID- 28745037
TI  - Risky Lifestyle Behaviors among Gastric Cancer Survivors Compared with Matched
      Non-cancer Controls: Results from Baseline Result of Community Based Cohort
      Study.
AB  - Purpose: This study investigated the prevalence of smoking, drinking, and
      physical inactivity and the associated factors of these behaviors in gastric
      cancer survivors. Materials and Methods: The baseline data from the nationwide
      cohort study was used. Four hundred thirty-seven gastric cancer survivors who
      survived >= 2 years from diagnosis and reported completion of treatment were
      matched with 4,370 controls according to age, sex, education, and household
      income. Results: The prevalence rates of current smoking and drinking among
      gastric cancer survivors were 8.7% and 38.3%, which were significantly lower than
      those among matched controls (p <= 0.001), but the prevalence rates of physical
      inactivity were not significantly different (55.8% vs. 59.9%, p=0.248). In
      gastric cancer survivors, >= 5 years since cancer diagnosis and current drinking
      contributed to more current smoking; otherwise, age increment and femalewere
      associatedwith lower current smoking. Thosewith household income >= $2,000 and
      current smokers were more likely to drink and female showed less drinking.
      Female, currently employed state, and self-rated health status were associated
      with more physical inactivity. Conclusion: Although gastric cancer survivors
      showed better health behaviors than controls, suggesting that the diagnosis of
      cancer may motivate individuals towards healthy behaviors, their current
      prevalence rates of smoking and drinking were still high, and more than 50% of
      them were physically inactive. Tailored interventions to improve their health
      behaviors considering associated factors for the gastric cancer survivors are
      necessary.

PMID- 28745038
TI  - Bilateral endoscopic surgery for renal stones: a systematic review of the
      literature.
AB  - INTRODUCTION: The aim of this study was to evaluate the current literature on
      single-session bilateral endoscopic surgery for renal stones, analyzing their
      effectiveness and safety. EVIDENCE ACQUISITION: A systematic literature review
      was performed to identify articles published between 1995 and July 2016 that
      reported data on bilateral single-session endoscopic surgery for renal stones.
      Articles were separated into the following categories: bilateral PCNL, bilateral
      FURS and bilateral PCNL with contralateral FURS. We used a narrative synthesis
      for the analyses of the studies. EVIDENCE SYNTESIS: Five reports of bilateral
      FURS were identified in the literature search. These studies included a total of
      218 patients that underwent bilateral FURS for renal stones. The primary SFR
      ranged from 64% to 92.8%. Postoperative complications were mostly described as
      minor complications; one major complication (0.5%) (grade V) was reported.
      Thirteen reports of bilateral PCNL were identified. These case studies included a
      total of 729 patients undergoing bilateral PCNL for renal stones. The primary SFR
      ranged from 24% to 100%. In all the studies a total of 29 (4%) major
      complications were described: 28 of them grade III while one was grade IV. One
      single study of bilateral PCNL with contralateral FURS for renal stones was
      identified. This report included 26 patients and the primary SFR was 92.3%. Two
      major complications (7.7%) (Grade III) were described. CONCLUSIONS: Bilateral
      single-session endoscopic procedures for bilateral renal stones are effective and
      safe. It should be considered a viable treatment option in carefully selected
      patients, performed by experienced urologists in high-volume centers. Key to
      success is the proper selection of patients and extending surgery on the second
      side only when the first side has been uneventful.

PMID- 28745039
TI  - Life-threatening complications: "the dark side" of ureteroscopy.

PMID- 28745040
TI  - Rough Electrode Creates Excess Capacitance in Thin-Film Capacitors.
AB  - The parallel-plate capacitor equation is widely used in contemporary material
      research for nanoscale applications and nanoelectronics. To apply this equation,
      flat and smooth electrodes are assumed for a capacitor. This essential assumption
      is often violated for thin-film capacitors because the formation of nanoscale
      roughness at the electrode interface is very probable for thin films grown via
      common deposition methods. In this work, we experimentally and theoretically show
      that the electrical capacitance of thin-film capacitors with realistic interface
      roughness is significantly larger than the value predicted by the parallel-plate
      capacitor equation. The degree of the deviation depends on the strength of the
      roughness, which is described by three roughness parameters for a self-affine
      fractal surface. By applying an extended parallel-plate capacitor equation that
      includes the roughness parameters of the electrode, we are able to calculate the
      excess capacitance of the electrode with weak roughness. Moreover, we introduce
      the roughness parameter limits for which the simple parallel-plate capacitor
      equation is sufficiently accurate for capacitors with one rough electrode. Our
      results imply that the interface roughness beyond the proposed limits cannot be
      dismissed unless the independence of the capacitance from the interface roughness
      is experimentally demonstrated. The practical protocols suggested in our work for
      the reliable use of the parallel-plate capacitor equation can be applied as
      general guidelines in various fields of interest.

PMID- 28745041
TI  - Correlation of Low-Frequency Noise to the Dynamic Properties of the Sensing
      Surface in Electrolytes.
AB  - Low-frequency noise (LFN) is of significant implications in ion sensing. As a
      primary component of LFN for ion sensing in electrolytes, the solid/liquid
      interfacial noise remains poorly explored especially regarding its relation to
      the surface binding/debinding dynamic properties. Here, we employ impedance
      spectroscopy to systematically characterize this specific noise component for its
      correlation to the dynamic properties of surface protonation (i.e., hydrogen
      binding) and deprotonation (i.e., hydrogen debinding) processes. This correlation
      is facilitated by applying our recently developed interfacial impedance model to
      ultrathin TiO2 layers grown by means of atomic layer deposition (ALD) on a TiN
      metallic electrode. With an excellent fitting of the measured noise power density
      spectra by the model for the studied TiO2 layers, we are able to extract several
      characteristic dynamic parameters for the TiO2 sensing surface. The observed
      increase of noise with TiO2 ALD cycles can be well accounted for with an
      increased average binding site density. This study provides insights into how
      detailed surface properties may affect the noise performance of an ion sensor
      operating in electrolytes.

PMID- 28745042
TI  - Single Palladium Nanoparticle Collisions Detection through Chronopotentiometric
      Method: Introducing a New Approach to Improve the Analytical Signals.
AB  - In the present research, the chronopotentiometric method and hydrazine, as a
      suitable probe, were used to detect single Pd nanoparticle (Pd-NP) collisions to
      the surface of a carbon fiber ultramicroelectrode (CFUME). The change in the
      potential, which is due to the electrocatalytic oxidation of hydrazine exactly at
      the time of Pd-NP collision to the CFUME surface, was used to detect each
      collide. It was shown that the amplitude and the frequency of the potential
      steps, produced through the nanoparticles collisions at the CFUME surface, are
      respectively proportional to their radius and concentration in an analytical
      solution. For the first time, a new approach is introduced for extraction of
      current-time plots (chronoamperograms) from experimental potential-time plots
      (chronopotentiograms). It is demonstrated that the signal-to-noise ratio (S/N)
      increases significantly based on the proposed method. Also, by using the
      chronoamperograms that resulted from the experimental chronopotentiograms, a
      higher number of collisions is achievable and, thus, the collision frequency, f,
      increases and the limit of detection decreases. Interestingly, the collision
      frequency resulted from the chronoamperograms, that has been derived from
      chronopotentiograms, is closer to the collision frequency calculated by using the
      theoretical model.

PMID- 28745043
TI  - Ehrlich Reaction Evoked Multiple Spectral Resonances and Gold Nanoparticle
      Hotspots for Raman Detection of Plant Hormone.
AB  - Surface-enhanced Raman scattering (SERS) by use of noble metal nanoparticles has
      become a powerful tool to determine a low-concentration target by unique spectral
      fingerprints, but it is still limited to the Raman-inactive and nonresonant
      biomolecules such as amine acids, proteins, and hormones. Here, we report an
      Ehrlich reaction based derivative strategy in combination with gold nanoparticles
      (Au NPs) hotspots for the selective detection of indole-like plant hormones by
      SERS spectroscopy. Ehrlich reaction of p-(dimethylamino)benzaldehyde (PDAB) with
      the indole ring chemically transformed plant hormone indole-3-butyric acid (IBA)
      into a Raman-active and resonant derivative with an extended pi-conjugated system
      in the form of a cation, which produced a new absorption band at 626 nm. On the
      other hand, cationic IBA-PDAB highly evoked the aggregation of Au NPs with
      negative citrate ligands to form the effective Raman hotspots and gave rise to
      the new absorption ranging from 600 to 800 nm. Significantly, the spectral
      overlap among IBA-PDAB, aggregated Au NPs, and the exciting laser initiated the
      multiple optical resonances to generate the ultrahigh Raman scattering with a
      sensitive limit of 2.0 nM IBA. The IBA in the whole sprouts and various parts of
      pea, mungbean, soybean, and black bean has been identified and quantified. The
      reported method opens a novel avenue for the SERS detection of Raman-inactive
      analyte by a proper derivation.

PMID- 28745044
TI  - Dynamically Cross-linked Elastomer Hybrids with Light-Induced Rapid and Efficient
      Self-Healing Ability and Reprogrammable Shape Memory Behavior.
AB  - Pristine carbon nanotubes (CNTs) were activated to exhibit Diels-Alder (DA)
      reactivity in a polymer matrix, which was modified with monomers containing furan
      groups. The DA-active polymer matrix was transferred into a dynamic reversible
      cross-linked inorganic-organic network via a Diels-Alder reaction with CNTs,
      where pristine CNTs were used as dienophile chemicals and furan-modified SBS
      acted as the macromolecular diene. In this system, the mechanical properties as
      well as resilience and solvent resistance were greatly improved even with the
      presence of only 1 wt % CNTs. Meanwhile, the hybrids retained recyclability and
      exhibited some smart behaviors, including self-healing and reprogrammable shape
      memory properties. Furthermore, due to the photothermal effect of CNTs, a retro
      Diels-Alder (rDA) reaction was activated under laser irradiation, and healing of
      a crack on the hybrid surface was demonstrated in approximately 10 s with almost
      complete recovery of the mechanical properties. Such fast and efficient self
      healing performance provides a new concept in designing self-healing
      nanocomposites with tunable structures and mechanical properties. Furthermore,
      the DA and rDA reactions could be combined to reprogram the shape memory behavior
      under laser irradiation or thermal treatment, wherein the temporary shape of the
      sample could be transferred to a permanent shape via the rDA reaction at high
      temperature.

PMID- 28745045
TI  - Versatile Solution-Processed Synthesis of Two-Dimensional Ultrathin Metal
      Chalcogenides Following Frank-van der Merwe Growth.
AB  - Two-dimensional (2D) ultrathin metal chalcogenides represent a class of promising
      materials for various applications thanks to attractive physicochemical
      properties. However, a reliable pathway for fabricating ultrathin metal
      chalcogenides nanosheets, regardless of the bulk crystals of their 3D
      counterparts, still remains a challenge. Herein, we present a versatile solution
      processed template synthesis strategy, in which a single molecular-level
      precursor anneals to ultrathin single-crystal nanosheets with the aid of lattice
      matching templates, following the Frank-van der Merwe growth mode and featuring
      high quality, low cost, scalability, and processability. Following this strategy,
      Sb2S3, MoS2, and ZnS nanosheets are successfully prepared as representatives for
      materials whose bulk counterparts possess 1D, 2D, and 3D crystal structures,
      respectively, and the growth mechanism is confirmed by crystal mode analysis. As
      a proof-of-concept application, MoS2 and Sb2S3 nanosheets are used for gas sensor
      and flexible photodetector applications, respectively, which exhibit excellent
      performance. The method can also be easily extended to other ultrathin nanosheets
      like single metals, metal oxide, metal nitride, and heterostructures.

PMID- 28745047
TI  - Photocontrolled Interconversion of Cationic and Radical Polymerizations.
AB  - The ability to combine two polymerization mechanisms in a one-pot setup and
      switch the monomer selectivity via an external stimulus provides an excellent
      opportunity to control polymer sequence and structure. We report a strategy that
      enables monomer incorporation to be determined via the selection of the
      wavelength of light through selective activation of either cationic or radical
      processes. This method enables the synthesis of varying polymeric structures
      under identical solution conditions but with simple modulation of the external
      stimulus. Additionally, changes in the ratios of the two photocatalysts afford
      complementary chemical control over these reactions to design elaborated
      polymeric structures. Our strategy takes advantage of the unique regulation that
      can be accessed through light.

PMID- 28745046
TI  - All-Atom MD Predicts Magnesium-Induced Hairpin in Chemically Perturbed RNA Analog
      of F10 Therapeutic.
AB  - Given their increasingly frequent usage, understanding the chemical and
      structural properties which allow therapeutic nucleic acids to promote the death
      of cancer cells is critical for medical advancement. One molecule of interest is
      a 10-mer of FdUMP (5-fluoro-2'-deoxyuridine-5'-O-monophosphate) also called F10.
      To investigate causes of structural stability, we have computationally restored
      the 2' oxygen on each ribose sugar of the phosphodiester backbone, creating
      FUMP[10]. Microsecond time-scale, all-atom, simulations of FUMP[10] in the
      presence of 150 mM MgCl2 predict that the strand has a 45% probability of folding
      into a stable hairpin-like secondary structure. Analysis of 16 MUs of data
      reveals phosphate interactions as likely contributors to the stability of this
      folded state. Comparison with polydT and polyU simulations predicts that
      FUMP[10]'s lowest order structures last for one to 2 orders of magnitude longer
      than similar nucleic acid strands. Here we provide a brief structural and
      conformational analysis of the predicted structures of FUMP[10], and suggest
      insights into its stability via comparison to F10, polydT, and polyU.

PMID- 28745048
TI  - Tautomerism-Induced Cis-Trans Isomerization of Pyridylethenyl N-Confused
      Porphyrin.
AB  - Pyridylethenyl-substituted N-confused porphyrins (NCPs) were synthesized, and
      their cis-trans isomerization was studied. Among four possible isomers, trans-3H
      and cis-2H types of structures, of which aromaticity and absorption/emission
      properties differ largely, were isolated. The cis-isomer was largely stabilized
      by the intramolecular hydrogen bonding between the pyrrolic-NH and the pyridinic
      N in the vicinity. The thermal cis-trans isomerization proceeded even at 30 
      degrees C, which was significantly accelerated by the pyridine added to the
      system. The kinetic studies revealed that the isomerization reaction was second
      order and the activation energy of the thermal isomerization from cis to trans
      isomer was DeltaG0?cis->trans = 35.7 kcal/mol at 298 K, which is significantly
      smaller than that of Ni complex (42.3 kcal/mol). An intermolecular proton
      transfer induced cis-trans isomerization mechanism was proposed.

PMID- 28745049
TI  - Removing Cross-Linked Telopeptides Enhances the Production of Low-Molecular
      Weight Collagen Peptides from Spent Hens.
AB  - The low-molecular-weight (LMW) peptides derived from collagen have shown a
      potential for various nutritional and pharmaceutical applications. However,
      production of LMW peptides from vertebrate collagen remains a challenge. Herein,
      we report a new method to produce LMW collagen peptides using pepsin pretreatment
      that removed cross-linked telopeptides in collagen molecules. After the
      pretreatment, the proportion of LMW collagen peptides (<1.4 kDa) that were
      obtained from pepsin-soluble collagen increased to 32.59% compared to heat
      soluble collagen peptides (16.10%). Fourier transform infrared spectroscopy
      results indicated that telopeptide cleavage retained the triple-helical
      conformation of collagen. Liquid chromatography-tandem mass spectrometry analysis
      suggested that Gly-X-Y (X is often proline, while Y is either hydroxyproline or
      hydroxylysine) repeats were not the main factors that hindered the enzymatic
      hydrolysis of collagen molecules. However, cross-link quantification demonstrated
      that trivalent cross-links that included pyridinolines and pyrroles were the
      primary obstacles to producing small peptides from collagen of spent hens. This
      study demonstrated for the first time that removing cross-linked telopeptides
      could enhance the production of LMW peptides from spent hen collagen, which is
      also of interest to manufacturers who produce LMW collagen peptides from other
      vertebrate animals, such as bovids and porcids.

PMID- 28745050
TI  - Fibronectin Conformation and Assembly: Analysis of Fibronectin Deletion Mutants
      and Fibronectin Glomerulopathy (GFND) Mutants.
AB  - To study fibronectin (FN) conformation and assembly, we generated several
      deletion mutants: FNDeltaI1-5, FNDeltaIII1-3, FNDeltaIII4-8, and FNDeltaIII11-14.
      A monomeric form, FNmono, which lacked the C-terminal dimerization region, was
      also created. FNtnA-D was generated by swapping FNIII domains 1-8 in FNDeltaIII11
      14 with seven FNIII domains from tenascin-C. The conformations of these mutants
      were analyzed by glycerol gradient sedimentation under low-salt (20 mM NaCl) and
      high-salt (200 mM NaCl) conditions. Surprisingly, most of the mutants showed a
      compact conformation under low-salt conditions, except for FNtnA-D. When we
      tested these mutants in cell culture, FNDeltaI1-5, FNDeltaIII1-3, and FNtnA-D
      were unable to form a matrix. Interestingly, FNDeltaIII1-3 and FNtnA-D were
      capable of co-assembly with full-length FN, while FNDeltaI1-5 was not. This
      indicates that the segment I1-5 is crucial for matrix assembly and segment III1-3
      is also important. Mutations in FN are associated with glomerulopathy, but when
      we studied mutant proteins, the single-nucleotide mutations had only minor
      effects on conformation and matrix assembly. The mutations may destabilize their
      FNIII domains or generate dimers of dimers by disulfide cross-linking.

PMID- 28745051
TI  - High-Performance Polymer Solar Cells Employing Rhodamines as Cathode Interfacial
      Layers.
AB  - The development of simple and water-/alcohol-soluble interfacial materials is
      crucial for the cost-effective fabrication process of polymer solar cells (PSCs).
      Herein, highly efficient PSCs are reported employing water-/alcohol-soluble and
      low-cost rhodamines as cathode interfacial layers (CILs). The results reveal that
      rhodamine-based CILs can reduce the work function of the Al cathode and
      simultaneously increase the open-circuit voltage, current density, fill factor,
      and power conversion efficiency (PCE) of PSCs. The solution-processed rhodamine
      based PSCs demonstrated a remarkable PCE of 10.39%, which is one of the best
      efficiencies reported for thieno[3,4-b]thiophene/benzodithiophene:[6,6]-phenyl
      C71-butyric acid methyl ester-based PSCs so far. The efficiency is also 42.3%
      higher than that of the vacuum-deposited Ca-based device (PCE of 7.30%) and 21.5%
      higher than that of the complicated solution-processable polymeric electrolyte
      poly[(9,9-bis(3-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9
      dioctylfluorene)]-based device (PCE of 8.55%). Notably, rhodamines are very
      economical and have been extensively used as dyes in industries. Our work
      indicates that rhodamines have shown a strong potential as CILs compared to their
      counterparts in the large-area fabrication process of PSCs.

PMID- 28745052
TI  - Identification of the TyrOH*+ Radical Cation in the Flavoenzyme TrmFO.
AB  - Tyrosine (TyrOH) and tryptophan radicals play important roles as intermediates in
      biochemical charge-transfer reactions. Tryptophanyl radicals have been observed
      both in their protonated cation form and in their unprotonated neutral form, but
      to date, tyrosyl radicals have only been observed in their unprotonated form.
      With a genetically modified form of the flavoenzyme TrmFO as a suitable model
      system and using ultrafast fluorescence and absorption spectroscopy, we
      characterize its protonated precursor TyrOH*+, and we show this species to have a
      distinct visible absorption band and a transition moment that we suggest to lie
      close to the phenol symmetry axis. TyrOH*+ is formed in ~1 ps by electron
      transfer to excited flavin and decays in ~3 ps by charge recombination. These
      findings imply that TyrOH oxidation does not necessarily induce its concerted
      deprotonation. Our results will allow disentangling of photoproduct states in
      flavoproteins in often-encountered complex situations and more generally are
      important for understanding redox chains relying on tyrosyl intermediates.

PMID- 28745053
TI  - Development of a MALDI-TOF MS-Based Protein Fingerprint Database of Common Food
      Fish Allowing Fast and Reliable Identification of Fraud and Substitution.
AB  - Fish substitution and fish fraud are widely observed in the global food market.
      To detect and prevent substitution, DNA-based methods do not always meet the
      demand of being time- and cost-efficient; therefore, methodology improvements are
      needed. The use of species-specific protein patterns, as determined by matrix
      assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry, has recently improved species identification of prokaryotes both
      time- and cost-wise. We used the method to establish a database containing
      protein patterns of common food fish prone to substitution. The database
      currently comprises 54 fish species. Aspects such as the sensitivity of
      identification on the species level and the impact of bacterial contamination of
      fish filets are assessed. Most database entries are characterized by low
      intraspecies but high interspecies variability. Hitherto, 118 validation samples
      were successfully determined. The results presented herein underline the
      potential and reliability of eukaryotic species identification via MALDI-TOF mass
      spectrometry.

PMID- 28745054
TI  - Chemically Functionalized Phosphorene: Two-Dimensional Multiferroics with
      Vertical Polarization and Mobile Magnetism.
AB  - In future nanocircuits based on two-dimensional (2D) materials, the ideal
      nonvolatile memories (NVMs) would be based on 2D multiferroic materials that can
      combine both efficient ferroelectric writing and ferromagnetic reading, which
      remain hitherto unreported. Here we show first-principles evidence that a halogen
      intercalated phosphorene bilayer can be multiferroic with most long-sought
      advantages: its "mobile" magnetism can be controlled by ferroelectric switching
      upon application of an external electric field, exhibiting either an "on" state
      with spin-selective and highly p-doped channels, or an "off" state, insulating
      against both spin and electron transport, which renders efficient electrical
      writing and magnetic reading. Vertical polarization can be maintained against a
      depolarizing field, rendering high-density data storage possible. Moreover, all
      those functions in the halogenated regions can be directly integrated into a 2D
      phosphorene wafer, similar to n/p channels formed by doping in a silicon wafer.
      Such formation of multiferroics with vertical polarization robust against a
      depolarizing field can be attributed to the unique properties of covalently
      bonded ferroelectrics, distinct from ionic-bonded ferroelectrics, which may be
      extended to other van der Waals bilayers for the design of NVM in future 2D
      wafers. Every intercalated adatom can be used to store one bit of data: "0" when
      binding to the upper layer and "1" when binding to the down layer, giving rise to
      a possible approach of realizing single atom memory for high-density data
      storage.

PMID- 28745055
TI  - Accurate Determination of the Absolute Isotopic Composition and Atomic Weight of
      Molybdenum by Multiple Collector Inductively Coupled Plasma Mass Spectrometry
      with a Fully Calibrated Strategy.
AB  - A fully calibrated strategy has been investigated for the first time for the
      accurate determination of absolute isotopic composition and atomic weight of
      molybdenum using multiple-collector inductively coupled plasma mass spectrometry.
      The correction for instrumental mass bias was performed using synthetic isotope
      mixtures, which were gravimetrically prepared with all of the seven high-purity
      and isotopically enriched molybdenum isotope materials together. Six natural
      molybdenum materials, including molybdenum standard solution NIST SRM 3134, were
      accurately measured and yielded the absolute isotopic composition (in atom %, k =
      1) of 92Mo-14.690(18), 94Mo-9.173(6), 95Mo-15.865(5), 96Mo-16.666(3), 97Mo
      9.588(4), 98Mo-24.307(16), and 100Mo-9.711(13). These isotopic data enable an
      atomic weight Ar(Mo) of 95.9466(34) (k = 2) to be calculated, which is slightly
      lower than the current standard atomic weight 95.95(1) and with a much improved
      uncertainty. The associated uncertainties were evaluated according to the Guide
      to Expression of Uncertainty in Measurement of ISO/BIPM and Monte Carlo
      simulation to ensure that all sources of uncertainty were fully accounted for. A
      particular characteristic of the proposed new approach is that mass bias
      correction factor K for each isotope ratio of molybdenum can be achieved via
      fully experimental determination without using the traditional semiempirical
      correction mathematical models. In addition, the relationship between mass of
      isotope and bias per mass unit beta was investigated based on the thorough
      measurement data.

PMID- 28745056
TI  - Ion-Pairing and Electrical Conductivity in the Ionic Liquid 1-n-Butyl-3
      methylimidazolium Methylsulfate [Bmim][MeSO4]: Molecular Dynamics Simulation
      Study.
AB  - Molecular dynamics simulations are performed on ionic liquid (IL) 1-n-butyl-3
      methylimidazolium methylsulfate. The calculated densities, diffusion
      coefficients, and electrical conductivities are in very good agreement with the
      experiment. While the Nernst-Einstein equation largely overestimates the
      electrical conductivities compared to experiment, its correction for the joint
      translation of counterions substantially improves its accuracy. Taking into
      account the role of correlated motions of ions, expressed in terms of the
      collective mean-squared-displacement, predicts electrical conductivities in close
      agreement with the experiment. An examination of different dynamical processes
      shows that three types of motions occur in this IL. Short relaxation times (<1
      ps) and low activation energies (~4 kJ mol-1) are associated with local
      structural properties such as hydrogen bonding. The second class, such as
      structural relaxation of hydrogen bonds, has longer relaxation times (a few ten
      picoseconds) and higher activation energies (~10 kJ mol-1). The slowest motions
      (relaxation times of a few ten nanoseconds and activation energies of ~35 kJ mol
      1) belong to the correlated motions of counterions. Ion-pairing, diffusion, and
      electrical conductivity belong to this third class. Closeness of the relaxation
      times and activation energies of the third class processes reveal that exchange
      of counterions in an ion's solvation shell governs the macroscopic dynamic
      properties of IL.

PMID- 28745057
TI  - Nanoscale Ion Pump Derived from a Biological Water Channel.
AB  - Biological molecular machines perform the work of supporting life at the smallest
      of scales, including the work of shuttling ions across cell boundaries and
      against chemical gradients. Systems of artificial channels at the nanoscale can
      likewise control ionic concentration by way of ionic current rectification,
      species selectivity, and voltage gating mechanisms. Here, we theoretically show
      that a voltage-gated, ion species-selective, and rectifying ion channel can be
      built using the components of a biological water channel aquaporin. Through all
      atom molecular dynamics simulations, we show that the ionic conductance of a
      truncated aquaporin channel nonlinearly increases with the bias magnitude,
      depends on the channel's orientation, and is highly cation specific but only for
      one polarity of the transmembrane bias. Further, we show that such an unusually
      complex response of the channel to transmembrane bias arises from mechanical
      motion of a positively charged gate that blocks cation transport. By combining
      two truncated aquaporins, we demonstrate a molecular system that pumps ions
      against their chemical gradients when subject to an alternating transmembrane
      bias. Our work sets the stage for future biomimicry efforts directed toward
      reproducing the function of biological ion pumps using synthetic components.

PMID- 28745058
TI  - Impact of Influenza A Virus Infection on the Proteomes of Human Bronchoepithelial
      Cells from Different Donors.
AB  - Susceptibility to influenza A virus is determined by a balance of viral and host
      factors. The genetic background of the host contributes to the severity of
      disease, but the influenza-related proteomes of cells from different individuals
      have not been compared. We used high-resolution mass spectrometry to identify
      proteins in normal human bronchial epithelial (NHBE) cells isolated from three
      different donors. Infection of each NHBE cell culture with influenza
      A/California/07/2009 (H1N1) resulted in expression of viral proteins and a
      variety of host proteins, including interferons, interferon-stimulated genes, and
      secreted chemokines/cytokines. The expression level of viral proteins
      corresponded to the level of host proteins that support influenza infection
      (i.e., pro-viral proteins); however, production of infectious virus was inversely
      related to the levels of antiviral proteins, suggesting that a balance of pro
      viral proteins and the antiviral response controls virus replication. In summary,
      our results demonstrate that expression levels of pro-viral as well as antiviral
      factors are different for each donor and suggest that relative quantitation of
      these factors may provide a way to identify individuals or population groups who
      are susceptible to severe influenza disease.

PMID- 28745059
TI  - Near-Infrared Neodymium Tag for Quantifying Targeted Biomarker and Counting Its
      Host Circulating Tumor Cells.
AB  - Quantitative information on a targeted analyte in a complex biological system is
      the most basic premise for understanding its involved mechanisms, and thus
      precise diagnosis of a disease if it is a so-called biomarker. Here, we designed
      and synthesized a neodymium (Nd)-cored tag [1,4,7,10-tetraazacyclododecane-1,4,7
      trisacetic acid (DOTA)-Nd complex together with a light-harvesting antenna
      aminofluorescein (AMF, lambdaex/em = 494/520 nm), AMF-DOTA-Nd] with duplex
      signals, second near-infrared (NIR) window luminescence (lambdaem = 1065 nm, 2.5
      MUs), and stable isotopic mass (142Nd). AMF-DOTA-Nd covalently linked with a urea
      based peptidomimetic targeting group, 2-[3-(1,3-dicarboxypropyl)
      ureido]pentanedioic acid (DUPA)-8-Aoc-Phe-Phe-Cys (DUPAaFFC) (DUPAaFFC-AMF-DOTA
      Nd), allowing us to detect and quantify prostate-specific membrane antigen (PSMA)
      and its splice variants (total PSMA, tPSMA), which was set as an example of
      targeted biomarkers in this study, using NIR and inductively coupled plasma mass
      spectrometry (ICPMS) with the limit of detection (LOD) (3sigma) of 0.3 ng/mL.
      When it was applied to the analysis of 80 blood samples from prostate cancer
      (PCa) and benign prostatic hyperplasia (BPH) patients as well as healthy
      volunteers, we found that 320 and 600 ng/mL tPSMA could be recommended as the
      threshold values to differentiate BPH from PCa and for the diagnosis of PCa.
      Moreover, PSMA-positive circulating tumor cells (CTCs) were counted using ICPMS
      being from 134 to 773 CTCs in the PCa blood samples of the Gleason score from 6
      to 9 when the cell membrane-spanning mPSMA was tagged. Such a methodology
      developed could be expected to be applicable to other clinic-meaningful
      biomolecules and their host CTCs in liquid biopsy, when other specific targeting
      groups are modified to the NIR Nd tag.

PMID- 28745060
TI  - Tunable Fluorescence of a Semiconducting Polythiophene Positioned on DNA Origami.
AB  - A novel approach for the integration of pi-conjugated polymers (CPs) into DNA
      based nanostructures is presented. Using the controlled Kumada catalyst-transfer
      polycondensation, well-defined thiophene-based polymers with controllable
      molecular weight, specific end groups, and water-soluble oligoethylene glycol
      based side chains were synthesized. The end groups were used for the easy but
      highly efficient click chemistry-based attachment of end-functionalized
      oligodeoxynucleotides (ODNs) with predesigned sequences. As demonstrated by
      surface plasmon resonance spectroscopy, the prepared block copolymers (BCPs),
      P3(EO)3T-b-ODN, comprising different ODN lengths and specific or repetitive
      sequences, undergo specific hybridization with complementary, thiol
      functionalized ODNs immobilized on a gold surface. Furthermore, the site-specific
      attachment of the BCPs to DNA origami structures is studied. We demonstrate that
      a nanoscale object, that is, a single BCP with a single ODN handle, can be
      directed and bound to the DNA origami with reasonable yield, site-specificity,
      and high spatial density. On the basis of these results, we are able to
      demonstrate for the first time that optical properties of CP molecules densely
      immobilized on DNA origami can be locally fine-tuned by controlling the
      attractive pi-pi-stacking interactions between the CPs. In particular, we show
      that the fluorescence of the immobilized CP molecules can be significantly
      enhanced by surfactant-induced breakup of pi-pi-stacking interactions between the
      CP's backbones. Such molecular control over the emission intensity of the CPs can
      be valuable for the construction of sophisticated switchable nanophotonic devices
      and nanoscale biosensors.

PMID- 28745061
TI  - Two-Dimensional Intrinsic Half-Metals With Large Spin Gaps.
AB  - Through a systematic search of all layered bulk compounds combined with density
      functional calculations employing hybrid exchange-correlation functionals, we
      predict a family of three magnetic two-dimensional (2D) materials with half
      metallic band structures. The 2D materials, FeCl2, FeBr2, and FeI2, are all
      sufficiently stable to be exfoliated from bulk layered compounds. The Fe2+ ions
      in these materials are in a high-spin octahedral d6 configuration leading to a
      large magnetic moment of 4 MUB. Calculations of the magnetic anisotropy show an
      easy-plane for the magnetic moment. A classical XY model with nearest neighbor
      coupling estimates critical temperatures, Tc, for the Berezinskii-Kosterlitz
      Thouless transition ranging from 122 K for FeI2 to 210 K for FeBr2. The quantum
      confinement of these 2D materials results in unusually large spin gaps, ranging
      from 4.0 eV for FeI2 to 6.4 eV for FeCl2, which should defend against spin
      current leakage even at small device length scales. Their purely spin-polarized
      currents and dispersive interlayer interactions should make these materials
      useful for 2D spin valves and other spintronic applications.

PMID- 28745062
TI  - Social Cost Bias, Probability Bias, and Self-Efficacy as Correlates of Behavioral
      Action in Social Anxiety.
AB  - The present study investigated the role of social cost bias, probability bias,
      and self-efficacy as correlates of behavioral action in a nonclinical sample of
      197 individuals, using a series of vignettes and self-report measures. The
      findings indicated that, as hypothesized, social cost bias, probability bias, and
      self-efficacy were associated with social anxiety. While social anxiety was
      associated with behavioral action, the three cognitive factors were associated
      with behavioral action above and beyond the contribution of social anxiety.
      However, contrary to the hypothesis, self-efficacy was the only cognitive factor
      directly associated with behavioral action when all variables were in the model.
      This information has implications for potential methods and target mechanisms for
      increasing client engagement with exposures and behavioral experiments in
      treatments for social anxiety.

PMID- 28745063
TI  - Home-based step training using videogame technology in people with Parkinson's
      disease: a single-blinded randomised controlled trial.
AB  - OBJECTIVES: To determine whether 12-week home-based exergame step training can
      improve stepping performance, gait and complementary physical and
      neuropsychological measures associated with falls in Parkinson's disease. DESIGN:
      A single-blinded randomised controlled trial. SETTING: Community (experimental
      intervention), university laboratory (outcome measures). SUBJECTS: Sixty
      community-dwelling people with Parkinson's disease. INTERVENTIONS: Home-based
      step training using videogame technology. MAIN MEASURES: The primary outcomes
      were the choice stepping reaction time test and Functional Gait Assessment.
      Secondary outcomes included physical and neuropsychological measures associated
      with falls in Parkinson's disease, number of falls over six months and self
      reported mobility and balance. RESULTS: Post intervention, there were no
      differences between the intervention ( n = 28) and control ( n = 25) groups in
      the primary or secondary outcomes except for the Timed Up and Go test, where
      there was a significant difference in favour of the control group ( P = 0.02).
      Intervention participants reported mobility improvement, whereas control
      participants reported mobility deterioration-between-group difference on an 11
      point scale = 0.9 (95% confidence interval: -1.8 to -0.1, P = 0.03). Interaction
      effects between intervention and disease severity on physical function measures
      were observed ( P = 0.01 to P = 0.08) with seemingly positive effects for the low
      severity group and potentially negative effects for the high-severity group.
      CONCLUSION: Overall, home-based exergame step training was not effective in
      improving the outcomes assessed. However, the improved physical function in the
      lower disease severity intervention participants as well as the self-reported
      improved mobility in the intervention group suggest home-based exergame step
      training may have benefits for some people with Parkinson's disease.

PMID- 28745064
TI  - Therapeutic potential of investigational CHK-1 inhibitors for the treatment of
      solid tumors.
AB  - INTRODUCTION: For several decades' cancer treatment targeting DNA repair pathways
      incorporated both chemo- and radiotherapy only. However, over the last decade
      improved knowledge of DNA repair processes has paved the way for the development
      of novel targeted drugs abrogating DNA repair signaling. Checkpoint kinase
      inhibitors are exciting molecules and hold promise in the treatment of both solid
      and hematologic malignancies. Herein, we discuss preclinical and clinical studies
      with this class of molecules. Areas covered: In this review, we discuss the role
      of check point kinase 1 (CHK-1) in DNA repair and provide a comprehensive summary
      of pre-clinical and early phase clinical trials with CHK-1 inhibitors. We also
      provide molecular structural basis of CHK-1inhibitors binding to CHK-1. Expert
      opinion: Available data from both pre-clinical and early clinical studies
      illustrates potential efficacy of this class of molecules when combined with
      antimetabolites in treating both solid and hematologic malignancies. In addition,
      there might be an additive role in combining this class of molecules to PARP
      inhibitors, platinum chemotherapy, or radiation therapy in p53 or BRCA mutated
      tumors. The safety of the aforementioned combination needs to be closely
      evaluated in the ongoing clinical trials.

PMID- 28745065
TI  - Assessment of Oral Anticoagulant Use in Residents of Long-Term Care Homes:
      Evidence for Contemporary Suboptimal Use.
AB  - OBJECTIVE: To describe the quality of warfarin use in residents of long-term care
      facilities and investigate potential predictors oral anticoagulant use. DESIGN:
      Retrospective chart review (August 2013 to September 2014). SETTING: Thirteen
      long-term care (LTC) and assisted living facilities (ALF). PARTICIPANTS:
      Residents from LTC or ALF settings who ( a) received warfarin or direct-acting
      oral anticoagulants (DOACs) and ( b) residents with a valid indication for oral
      anticoagulants such as atrial fibrillation, venous thromboembolism, but were not
      receiving these drugs. PRIMARY OUTCOME: Time in therapeutic international
      normalized ratio (INR) range (TTR). RESULTS: A total of 563 residents (70%
      female) with an average age of 85 years were identified. Participants had an
      average of 7.5 comorbidities and 9 medications. A total of 391 (69%) residents
      with indications for OACs were receiving such medications. Indications were
      atrial fibrillation (63%), venous or pulmonary embolism (16%), cardiac valves
      (0.4%); 26% did not have documented indications. Warfarin and DOACs were
      prescribed for 213 (38%) and 178 (32%) respectively, and 172 (31%) received no
      OACs The TTR ranged from 56%-75% (mean 63%). The frequency of INR determinations
      ranged from every 7 to 20 days, (mean 13 days) with no apparent relationship
      between frequency of testing and TTR. CONCLUSION: The TTR was higher (63.8%) than
      literature average (50%), but remains suboptimal given expected benefits of TTRs
      >75% versus TTRs circa 60%. Documentation of indications for OACs needs
      improvement, and it is possible that OACs are underused. Further work is
      necessary to understand how OAC use may be optimized in these facilities.

PMID- 28745067
TI  - Participants' Understanding of Informed Consent for Biobanking: A Systematic
      Review.
AB  - Nurses are increasingly asked to obtain consent from participants for biobanking
      studies. Biobanking has added unique complexities to informed consent. The
      purpose of this systematic review was to evaluate participants' level of
      understanding of the information presented during the informed consent process
      unique to the donation of biological specimens for research. The Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were
      utilized to conduct the review. PubMed, EMBASE, CINAHL, PsycINFO, Scopus, Web of
      Science, and ProQuest bibliographic databases were searched. Results indicated
      that elements of informed consent unique to biobanking were poorly understood.
      Most studies had authors or funding associated with a biobank. Only one study
      disclosed and assessed participants' understanding of moral risks. Increased
      disclosures, values-clarification, and presenting information via multiple
      modalities may facilitate understanding. There is a need to improve the quality
      of informed consent for biobanking studies by utilizing standardized instruments,
      definitions, and encouraging research about informed choice outside the
      biobanking industry.

PMID- 28745066
TI  - A Comparison of the Efficacy and Tolerability of the Treatments for Sciatica: A
      Network Meta-Analysis.
AB  - BACKGROUND: There remains a lack of a systematic summary of the efficacy and
      safety of various medicines for sciatica, and discrepancies among these exist.
      OBJECTIVE: The aim of this study is to comprehensively assess the efficacy of and
      tolerance to several medical options for the treatment of sciatica. METHODS: We
      performed a network meta-analysis and illustrated the results by the mean
      difference or odds ratio. The surface under the cumulative ranking curve (SUCRA)
      was used for indicating the preferable treatments. All data analyses and graphs
      were achieved via R 3.3.2 and Stata 13.0. RESULTS: The subcutaneous anti-tumor
      necrosis factor-alpha (anti-TNF-alpha) was superior to the epidural steroid +
      anesthetic in reducing lumbar pain in both acute + chronic sciatica patients and
      acute sciatica patients. The epidural steroid demonstrated a better ability
      regarding the Oswestry disability score (ODI) compared to the subcutaneous anti
      TNF-alpha. In addition, for total pain relief, the use of nonsteroidal
      antiinflammatory drugs was inferior to the epidural steroid + anesthetic. The
      epidural anesthetic and epidural steroid + anesthetic both demonstrated
      superiority over the epidural steroid and intramuscular steroid. The intravenous
      anti-TNF-alpha ranked first in leg pain relief, while the subcutaneous anti-TNF
      alpha ranked first in lumbar pain relief, and the epidural steroid ranked first
      in the ODI on the basis of SUCRA. In addition, their safety outcome (withdrawal)
      rankings were all medium to high. CONCLUSIONS: Intravenous and subcutaneous anti
      TNF-alpha were identified as the optimal treatments for both acute + chronic
      sciatica patients and acute sciatica patients. In addition, the epidural steroid
      was also recommended as a good intervention due to its superiority in reducing
      ODI.

PMID- 28745068
TI  - Arthroscopic Capsular Shrinkage for Treatment of Chronic Lateral Ankle
      Instability.
AB  - BACKGROUND: Capsular shrinkage is an arthroscopic stabilization technique that
      can be used in patients with chronic ankle instability (CAI), if desired in
      addition to primary arthroscopic procedures. Despite positive short-term results,
      long-term follow-up of these patients has not yet been performed. Therefore, our
      objective was to assess whether capsular shrinkage still provided functional
      outcome after 12-14 years compared to preoperative scores. METHODS: This study
      was a retrospective long-term follow-up of a prospectively conducted longitudinal
      multicenter trial. The study duration was from February 2002 to September 2016,
      including a preoperative assessment and short-, mid-, and long-term follow-up. At
      the time of inclusion, patients were diagnosed with CAI, >18 years old, were
      unresponsive to conservative treatment, and had confirmed mechanical ankle joint
      laxity. Patients were excluded if the talar tilt was greater than 15 degrees, if
      they had received previous operative treatment, or had constitutional
      hyperlaxity, systemic diseases, or osteoarthritis grade II or III. The primary
      outcome was the change in functional outcome as assessed by the Karlsson score.
      RESULTS: Twenty-five patients of the initial 39 were available for this follow
      up. This group had a mean age of 43.2 years (SD+/-11.1) and included 15 males. A
      statistically significant improvement was found in the Karlsson score at 12-14
      years (76.6 points; SD+/-25.5) relative to the preoperative status (56.4 points;
      SD +/-13.3; P < .0005). Although 17 patients (68%) reported recurrent sprains, 23
      patients (92%) stated that they were satisfied with the procedure. CONCLUSIONS:
      Despite improved functional outcome and good satisfaction in patients with CAI
      after capsular shrinkage, recurrence rates and residual symptoms were high. For
      this reason, arthroscopic capsular shrinkage is not recommended as joint
      stabilization procedure in patients with CAI. LEVEL OF EVIDENCE: Level IV, case
      series.

PMID- 28745069
TI  - A case series of PLS patients with frontotemporal dementia and overview of the
      literature.
AB  - OBJECTIVE: Primary lateral sclerosis (PLS) is a rare form of motor neuron disease
      characterised by UMN degeneration leading to slowly progressive spasticity.
      Whether it is a separate disease or a subtype of ALS has been debated. In ALS
      comorbid frontotemporal dementia (FTD) is frequently seen (+/-15%). However,
      cognitive and behavioural changes are generally not considered to be a part of
      PLS. METHODS: To report the clinical findings and frequency of PLS patients that
      developed FTD in a referral-based cohort and provide an overview of the
      literature. RESULTS: In our cohort six out of 181 (3.3%) PLS patients developed
      FTD. In the literature a few cases of PLS with FTD have been reported and only a
      limited number of small studies have investigated cognition in PLS. However, when
      these studies are summarised a pattern emerges with FTD diagnoses in +/-2% and
      frontotemporal impairment in 22% of patients. CONCLUSIONS: These findings suggest
      that PLS is part of the FTD-MND continuum and would favour viewing it as a
      subtype of ALS. It is, however, not a restricted (isolated UMN involvement)
      phenotype.

PMID- 28745070
TI  - Management options for cholestatic liver disease in children.
AB  - INTRODUCTION: Due to a peculiar age-dependent increased susceptibility, neonatal
      cholestasis affects the liver of approximately 1 in every 2500 term infants. A
      high index of suspicion is the key to an early diagnosis, and to implement
      timely, often life-saving treatments. Even when specific treatment is not
      available or curative, prompt medical management and optimization of nutrition
      are of paramount importance to survival and avoidance of complications. Areas
      covered: The present article will prominently focus on a series of newer
      diagnostic and therapeutic options of cholestasis in neonates and infants blended
      with consolidated established paradigms. The overview of strategies for the
      management reported here is based on a systematic literature search published in
      English using accessible databases (PubMed, MEDLINE) with the keywords biliary
      atresia, choleretics and neonatal cholestasis. References lists from retrieved
      articles were also reviewed. Expert commentary: A large number of uncommon and
      rare hepatobiliary disorders may present with cholestasis during the neonatal and
      infantile period. Potentially life-saving disease-specific pharmacological and
      surgical therapeutic approaches are currently available. Advances in
      hepatobiliary transport mechanisms have started clarifying fundamental aspects of
      inherited and acquired cholestasis, laying the foundation for the development of
      possibly more effective specific therapies.

PMID- 28745071
TI  - Olaratumab for the treatment of soft-tissue sarcoma.
AB  - The outcome for patients with unresectable/metastatic soft tissue sarcoma remains
      poor with few treatment options. In the first line setting, a number of
      randomized trials have shown no difference in overall survival between
      combination anthracycline schedules and single agent doxorubicin. A Phase
      Ib/randomized Phase II trial of doxorubicin with or without the monoclonal
      antibody to PDGFR-alpha, olaratumab, demonstrated a significant difference in
      median overall survival in favor of the olaratumab arm. The results of this trial
      led to approval of olaratumab in combination with doxorubicin in adult
      anthracycline-naive unresectable soft tissue sarcoma. In this review, we describe
      some of the preclinical and early clinical data of olaratumab in sarcomas, the
      Phase Ib/II trial and ongoing trials with olaratumab in sarcomas.

PMID- 28745073
TI  - Current and future options for cytomegalovirus reactivation in hematopoietic cell
      transplantation patients.
AB  - Report from the 43rd Annual Meeting of the European Society for Blood & Marrow
      Transplantation 2017, 26-29 March 2017, Marseille, France Cytomegalovirus (CMV)
      reactivation is a potentially life-threatening complication in immunocompromised
      recipients of hematopoietic cell transplantation (HCT). Its management was
      therefore a key topic for over 5000 delegates from 85 countries attending the
      43rd Annual Meeting of the European Society for Blood & Marrow Transplantation
      2017. The currently available anti-CMV armamentarium is seldom used to prevent
      CMV reactivation due to the associated myelosuppression and renal toxicity.
      Following HCT, CMV reactivation is generally managed pre-emptively using
      sensitive assays for early detection of viral DNA (and to a lesser extent
      antigenemia) and, where necessary, treatment with antiviral drugs with the aim of
      preventing CMV disease. However, any degree of CMV reactivation increases the
      risk of mortality, and novel antiviral therapies may offer the possibility of
      prophylaxis to prevent CMV reactivation and improve survival after HCT.

PMID- 28745072
TI  - Assessment of Somatization and Medically Unexplained Symptoms in Later Life.
AB  - The assessment of medically unexplained symptoms and "somatic symptom disorders"
      in older adults is challenging due to somatic multimorbidity, which threatens the
      validity of somatization questionnaires. In a systematic review study, the
      Patient Health Questionnaire-15 (PHQ-15) and the somatization subscale of the
      Symptom Checklist 90-item version (SCL-90 SOM) are recommended out of 40
      questionnaires for usage in large-scale studies. While both scales measure
      physical symptoms which in younger persons often refer to unexplained symptoms,
      in older persons, these symptoms may originate from somatic diseases. Using
      empirical data, we show that PHQ-15 and SCL-90 SOM among older patients correlate
      with proxies of somatization as with somatic disease burden. Updating the
      previous systematic review, revealed six additional questionnaires. Cross
      validation studies are needed as none of 46 identified scales met the criteria of
      suitability for an older population. Nonetheless, specific recommendations can be
      made for studying older persons, namely the SCL-90 SOM and PHQ-15 for population
      based studies, the Freiburg Complaint List and somatization subscale of the Brief
      Symptom Inventory 53-item version for studies in primary care, and finally the
      Schedule for Evaluating Persistent Symptoms and Somatic Symptom Experiences
      Questionnaire for monitoring treatment studies.

PMID- 28745074
TI  - Dementia looming!
AB  - Background I, the 45-year-old scientist, the PhD, the sublime researcher, now
      subject to dementia? I felt confused, very ashamed and told no one, until they
      found out. I suffer from brain atrophy, associated with multiple sclerosis I am
      suffering from for years. My cognitive impairment is the result of my shrinking
      brain! Objectives With my personal view 'Dementia Looming!', I hope to contribute
      to and support healthcare professionals and scientists in understanding the
      meaning of dementia. Although not scientific, my paper gives a unique behind-the
      scenes view into what it means to experience dementia symptoms.

PMID- 28745075
TI  - Outcomes of Lisfranc Injuries in an Active Duty Military Population.
AB  - BACKGROUND: Traumatic injuries to the tarsometatarsal or Lisfranc joints can be
      complex problems associated with long-term morbidity. Currently there is no clear
      consensus regarding optimal fixation methods. The purpose of this study was to
      evaluate the association between time from injury to treatment and treatment
      method with outcome. It is hypothesized that patients who underwent open
      reduction internal fixation (ORIF) more acutely would have higher return to duty
      rates. METHODS: This study is a retrospective review of 171 low-energy closed
      tarsometatarsal dislocations and fracture dislocations in patients identified
      using a Department of Defense trauma registry. Outcomes were defined as return to
      active duty and separation from service. Patients were categorized into cohorts
      by surgical treatment: ORIF, primary arthrodesis (PA), or having required a
      salvage arthrodesis (SA). RESULTS: The data demonstrate no significant difference
      between ORIF and PA as well as significantly lower return to duty rates in those
      who underwent SA. There was no association between increased time from injury to
      treatment and the observed outcomes. CONCLUSION: This study not only reinforces
      the importance of initial anatomic reduction and the poor outcomes of
      posttraumatic osteoarthritis but also suggests that SA portends poor outcomes in
      a highly active population. Most notably it found no significant difference in
      return to duty rates between ORIF and PA despite the inclusion of more "missed"
      and chronic injuries in the PA group. This suggests that PA may be a viable
      option in a young and active population regardless of treatment timing. LEVEL OF
      EVIDENCE: Level III, retrospective comparative series.

PMID- 28745076
TI  - Effects of ICI204,448, naloxone methiodide and levocetirizine on the scratching
      behavior induced by a kappa-opioid antagonist, nor-BNI, in ICR mice.
AB  - OBJECTIVE: In this study, we aimed to study the effects of ICI204,448, naloxone
      methiodide and levocetirizine on the scratching behavior induced by intradermal
      injection of a ?-opioid antagonist, nor-binaltorphimine (nor-BNI), into the
      rostral back of ICR mice were investigated. MATERIALS AND METHODS: Male ICR mice
      weighing 30?35 g were used. The number of scratching episodes were counted for 60
      min after i.d. injection of nor-BNI. RESULTS: nor-BNI dose dependently increased
      in the number of scratching episodes in ICR mice. nor-BNI-induced scratching
      behavior was inhibited by not only nalfurafine but also ICI204,448, a
      peripherally selective ?-opioid agonist. Naloxone and naloxone methiodide, a
      peripherally restricted ?-opioid antagonist, also inhibited nor-BNI-induced
      scratching behavior. Scratching behavior induced by nor-BNI was inhibited by
      chlorpheniramine as well as levocetirizine, a third-generation H1 antagonist that
      does not cross into the CNS. CONCLUSION: These results suggest that scratching
      behavior induced by this ?-opioid antagonist, nor-BNI, is related to not only
      central but also peripheral opioid and H1 receptors.

PMID- 28745077
TI  - Validity of a protocol to estimate patients' pre-morbid basal blood pressure.
AB  - PURPOSE: The pre-illness basal mean arterial BP (MAP) is an important reference
      point to gauge the degree of relative hypotension among unwell patients. We aimed
      to assess mean bias, correlation, and agreement between basal MAP measured during
      nighttime ambulatory BP monitoring (ABPM) and basal MAP estimated using a
      standardized protocol. MATERIALS AND METHODS: For a cohort of 137 consecutive
      patients, aged >=40 years, who recently underwent ABPM, a blinded investigator
      estimated basal MAP from up to five most recent clinic BP measurements. Both
      basal MAP values, measured and estimated, were compared pairwise for each
      participant. RESULTS: We traced a median of 4 [interquartile range 3-5] previous
      BP measurements per patient over a median period of 132 [interquartile range 55
      277] days up until the ABPM test. The estimated basal MAP (mean 88 +/- 8 mmHg)
      was linearly related (Pearson's r = 0.41, p = 0.0001) to the measured basal MAP
      (mean 88 +/- 12 mmHg). Bland-Altman plot revealed a mean bias of 0.3 mmHg with
      agreement limits of +/-22 mmHg. CONCLUSIONS: The mean bias between estimated and
      measured values for basal MAP was insignificant and modest. When a recent
      nighttime ABPM is unavailable, a protocol based on recent clinic BP readings can
      be used to estimate patient's basal MAP. STUDY REGISTRATION: Australian New
      Zealand Clinical Trials Registry ACTRN12613001382763.

PMID- 28745078
TI  - Hair cortisol in relation to acute and post-traumatic stress symptoms in children
      and adolescents.
AB  - BACKGROUND: We report on the preliminary results of two independent studies that
      (1) compare the hair cortisol concentrations (HCC) of healthy controls with
      patients displaying post-traumatic stress symptoms (PTSS, study 1+2), (2)
      investigate whether pre-trauma HCC are predictive for the development of acute
      stress symptoms (ASS) and PTSS (study 1) and (3) determine whether HCC correlate
      with PTSS in a clinical sample of children (study 2). METHODS: In study 1, the
      clinical symptoms of 35 minors were examined one (T1) and seven weeks (T2) after
      surgery following an accident. Hair samples were taken after the accident that
      reflect cortisol secretion over the past three months before the accident
      (healthy controls). In study 2, HCC and PTSS symptoms were cross-sectionally
      assessed in 22 minors who had experienced a psychological trauma. RESULTS: The
      HCC of patients with PTSS were lower than the HCC of healthy controls (study
      1+2). Secondary analyses showed that HCC were significantly lower in male PTSS
      patients than in male healthy controls, whereas the HCC in females were
      comparably low in both groups. Pre-trauma HCC did not predict the total ASS and
      PTSS scores (study 1) and HCC were not directly related to the total PTSS scores
      (study 2).

PMID- 28745079
TI  - Cytokine production in mammary adenocarcinoma and its microenvironmental cells in
      patients with or without metastases in regional lymph nodes.
AB  - In recent years, the concept of formation of a sufficiently autonomous cytokine
      network in a malignant tumour has emerged. In this regard, the data on the role
      of this network and its signalling pathways in the process of metastasis are an
      interesting topic. The aim of this study was to evaluate the in vitro cytokine
      producing potential of mammary adenocarcinoma (MAC; and cells of its
      microenvironment) from patients with or without metastases in regional lymph
      nodes (LNs). By enzyme-linked immunosorbent assays of culture supernatants, we
      studied the cytokine production by biopsy samples of MAC: spontaneous and
      stimulated by polyclonal activators (PAs: phytohaemagglutinin, concanavalin A and
      lipopolysaccharide). The levels of spontaneous production of interleukin (IL)-10
      and granulocyte colony-stimulating factor (G-CSF) and the amounts of IL-2, IL-10,
      G-CSF and monocyte chemoattractant protein-1 (MCP-1) produced during stimulation
      by PAs, as well as the index of stimulation by polyclonal activators (ISPA) for
      IL-2 production, were lower for MAC with LN metastasis than for MAC without LN
      metastasis. The levels of spontaneous production of IL-2 and interferon (IFN)
      gamma and the ISPA for granulocyte-macrophage colony-stimulating factor (GM-CSF)
      production were higher for MAC with LN metastasis. There were only three pairwise
      correlations between the produced cytokines that were specific to MAC with LN
      metastasis: IL-2 and IFN-gamma, IL-6 and GM-CSF, and IL-8 and GM-CSF. There were
      10 pairwise correlations between the produced cytokines that were specific to
      nonmetastasising MAC: IL-6 and IL-10, IL-6 and MCP-1, IL-8 and IL-10, IL-8 and
      MCP-1, IL-10 and G-CSF, IL-10 and MCP-1, IFN-gamma and MCP-1, MCP-1 and G-CSF, G
      CSF and IL-1Ra, and GM-CSF and tumour necrosis factor (TNF)-alpha. Our data
      indicate that metastatic tumours show desynchronisation of many pathways of
      induction and synthesis of cytokines that are characteristic of nonmetastatic
      tumours.

PMID- 28745080
TI  - Improving understanding of trigger points and widespread pressure pain
      sensitivity in tension-type headache patients: clinical implications.
AB  - INTRODUCTION: The underlying etiology of tension type headache (TTH) is not
      understood. The current paper highlights the etiologic role of muscle trigger
      points (TrPs) to the development and maintenance of central sensitization in TTH
      and its clinical repercussion for proper management of these patients. Areas
      covered: A literature search on Pub Med for English-language published papers
      between 1990 and May 2017 to provide the most updated data on the topic was
      conducted. Current literature suggests that the referred pain elicited by active
      trigger points (TrPs) contributes to the manifestations of TTH. There is also
      evidence supporting that TrPs represent a peripheral source of nociception and
      thereby a driver in the development of central sensitization. In fact, TrPs have
      been found to be associated with widespread pressure pain sensitivity in TTH.
      Temporal and spatial summation of TrP nociception suggests that inactivating TrP
      in the neck, head and shoulder muscles could help these patients; however,
      current evidence supporting the therapeutic role of TrPs in TTH is conflicting.
      Expert commentary: Understanding the role of TrPs in TTH in widespread pain
      sensitization may help to develop better management regimes and possibly prevent
      TTH from developing into more chronic conditions.

PMID- 28745081
TI  - Ethnobotanical, Ethnopharmacological, and Phytochemical Studies of Myrtus
      communis Linn: A Popular Herb in Unani System of Medicine.
AB  - Myrtus communis L (Myrtaceae) is one of the popular drugs being used in the Unani
      system of phytomedicine since ancient Greece period. From time immemorial,
      different parts of this plant and essential oil have been used for a variety of
      purposes such as cosmetics (hair fall control), flavoring of food and drinks as
      well as extensive therapeutic purposes. Ethnobotanical information revealed that
      M communis L has been a folkloric repute for the treatment of several diseases
      like gastric ulcer, diarrhea, dysentery, cancer, rheumatism, hemorrhage, deep
      sinuses, leucorrhoea, hemorrhoid, inflammation, dyspepsia, anxiety, insomnia,
      diabetes, hypertension, pulmonary disorders, and skin diseases. Moreover,
      ethnopharmacological studies revealed that the plant is endowed with extensive
      pharmacological activities, including antimicrobial, antidiarrheal, antidiabetic,
      antispasmodic, vasodilator, antiulcer, antioxidant, anticancer, anxiolytic,
      sedative-hypnotic, and anti-inflammatory activities, among others. The plant has
      been known to contain phenolic acids, tannins, flavonoids, glycosides, and
      terpenes. The myrtle oil was also found to be rich in a variety of bioactive
      monoterpenes and sesquiterpenes with their derivatives. Most of these studies
      validate the aforementioned traditional claims of this medicinal plant. Further
      studies are needed to unravel other pharmacological activities of this plant in
      the long run.

PMID- 28745082
TI  - Chinese Herbal Medicine, Jian Pi Li Gan Decoction, Improved Survival of
      Nonresectable Hepatocellular Cancer After Radiofrequency Ablation: A
      Retrospective Study.
AB  - OBJECTIVE: To observe the effect of Jian Pi Li Gan Decoction (JPLGD) on long-term
      survival of nonresectable hepatocellular cancer (HCC) after radiofrequency
      ablation (RFA). METHODS: Between January 2010 and February 2013, 95 patients with
      nonresectable HCC treated by RFA in our hospital were enrolled, of whom 47
      patients received JPLGD accompanying RFA (JPLGD group), and 48 patients received
      RFA alone (control group). Medical records of these patients were retrospectively
      analyzed. Long-term survival, complication, and treatment event were compared.
      RESULTS: Baseline characteristics did not differ between the 2 groups. No
      significant adverse effects or toxicities related to herbal medicine were found.
      The JPLGD group had significantly less liver failure (3/47 vs 10/48, P = .0405)
      and a higher treatment success rate than the control group (44/47 vs 37/48, P =
      .0230). The 3-year overall survival probability was significantly higher in the
      JPLGD group ( P = .0175). CONCLUSION: JPLGD has the potential to effectively and
      safely improve long-term survival of nonresectable HCC by increasing treatment
      success of RFA.

PMID- 28745083
TI  - Elemental Diet Accelerates the Recovery From Oral Mucositis and Dermatitis
      Induced by 5-Fluorouracil Through the Induction of Fibroblast Growth Factor 2.
AB  - Mucositis and dermatitis induced by anticancer agents are common complications of
      anticancer therapies. In this study, we evaluated the efficacy of Elental
      (Ajinomoto Pharmaceutical Ltd, Tokyo, Japan), an elemental diet with glutamine in
      the treatment of 5-fluorouracil (5-FU)-induced oral mucositis and dermatitis in
      vivo and tried to clarify the underlying mechanisms of its action. Oral mucositis
      and dermatitis was induced through a combination of 5-FU treatment and mild
      abrasion of the cheek pouch in hamsters and the dorsal skin in nude mice
      respectively. These animals received saline, dextrin or Elental suspension (18
      kcal/100 g) by a gastric tube daily until sacrifice. Elental reduced oral
      mucositis and dermatitis more effectively than dextrin in the animal model.
      Moreover, growth facilitating effects of Elental on HaCaT cells were examined in
      vitro. MTT assay, wound healing assay, and migration assay revealed that Elental
      could enhance the growth, invasion, and migration ability of HaCaT. ELISA and
      Western blotting showed upregulated FGF2 in Elental-treated HaCaT. These findings
      suggest that Elental is effective for the treatment of mucositis and dermatitis,
      and may accelerate mucosal and skin recovery through FGF2 induction and
      reepithelization.

PMID- 28745084
TI  - Patient With Unresectable Cholangiocarcinoma Treated With Radiofrequency
      Hyperthermia in Combination With Chemotherapy: A Case Report.
AB  - Hyperthermia, which is a noninvasive treatment that causes tumor cells to become
      heated and that works in synergy with anticancer drugs and radiation therapy, is
      emerging as a promising treatment for patients with cancer. The purpose of this
      study is to report the efficacy of hyperthermia combined with chemotherapy
      (gemcitabine/cisplatin) for the treatment of a patient with unresectable
      cholangiocarcinoma. A 54-year-old man was diagnosed as hilar cholangiocarcinoma
      (Klatskin tumor) and was administered neoadjuvant and preoperative radiation with
      chemotherapy. However, because the treatment with radiation and chemotherapy was
      not successful, he decided to undergo hyperthermia combined with chemotherapy as
      a second treatment option. He was suffering from fatigue, dyspepsia,
      epigastralgia, and jaundice. Hyperthermia combined with chemotherapy was
      administered 32 times over a period of 4 months. The patient experienced no
      critical complications, and the patient's condition improved, with the
      carbohydrate antigen 19-9 (CA 19-9) and the total bilirubin levels being
      relatively lowered. In addition, the computed tomography scan showed that the
      cholangiocarcinoma had not progressed. In conclusion, this case report suggests
      radiofrequency hyperthermia combined with chemotherapy may be a promising
      treatment option for patients with unresectable cholangiocarcinoma.

PMID- 28745085
TI  - Deep Lancing or Overmanipulation?

PMID- 28745086
TI  - Fog Computing and Edge Computing Architectures for Processing Data From Diabetes
      Devices Connected to the Medical Internet of Things.
AB  - The Internet of Things (IoT) is generating an immense volume of data. With cloud
      computing, medical sensor and actuator data can be stored and analyzed remotely
      by distributed servers. The results can then be delivered via the Internet. The
      number of devices in IoT includes such wireless diabetes devices as blood glucose
      monitors, continuous glucose monitors, insulin pens, insulin pumps, and closed
      loop systems. The cloud model for data storage and analysis is increasingly
      unable to process the data avalanche, and processing is being pushed out to the
      edge of the network closer to where the data-generating devices are. Fog
      computing and edge computing are two architectures for data handling that can
      offload data from the cloud, process it nearby the patient, and transmit
      information machine-to-machine or machine-to-human in milliseconds or seconds.
      Sensor data can be processed near the sensing and actuating devices with fog
      computing (with local nodes) and with edge computing (within the sensing
      devices). Compared to cloud computing, fog computing and edge computing offer
      five advantages: (1) greater data transmission speed, (2) less dependence on
      limited bandwidths, (3) greater privacy and security, (4) greater control over
      data generated in foreign countries where laws may limit use or permit unwanted
      governmental access, and (5) lower costs because more sensor-derived data are
      used locally and less data are transmitted remotely. Connected diabetes devices
      almost all use fog computing or edge computing because diabetes patients require
      a very rapid response to sensor input and cannot tolerate delays for cloud
      computing.

PMID- 28745087
TI  - Accuracy Evaluation of a Blood Glucose Monitoring System According to EN ISO
      15197:2015.

PMID- 28745088
TI  - Replacement of Blood Glucose Measurements by Measurements With Systems for Real
      Time Continuous Glucose Monitoring (rtCGM) or CGM With Intermittent Scanning
      (iscCGM): A German View.

PMID- 28745089
TI  - Barriers to Patient Use of Control Solution for Glucose Meters: Surveys of
      Patients, Pharmacists, and Providers in a Metropolitan Area.
AB  - BACKGROUND: An important factor in controlling diabetes is self-monitoring of
      blood glucose. Manufacturers of glucose meters recommend routine use of control
      solution to ensure accuracy. Previous studies have demonstrated that glucose
      meters vary in accuracy and that patients are not using control solution as
      recommended. The purpose of this study is to identify potential barriers to
      control solution use from multiple perspectives including patient, pharmacist,
      and provider. METHODS: This study was a prospective, observational survey design.
      First, 25 randomly selected chain and independent pharmacies in the Tulsa
      metropolitan area were audited for control solution accessibility. These
      pharmacies were then used to survey pharmacists, via telephone, regarding control
      solution inventory and perception of importance of use. Next, providers were
      electronically surveyed on their routine practice recommendations, while 60
      patients with diabetes were randomly selected for telephone survey on use and
      perceptions of control solution. RESULTS: Twenty-five pharmacies were audited and
      23 pharmacists, 60 patients, and 29 providers were surveyed. Only 39% of
      pharmacies stated they supplied control solution, however, only 1 pharmacy
      visibly stocked it. The only patient factor that appeared to have an impact on
      control solution usage was having type 1 versus type 2 diabetes (38% vs 15%).
      Providers are aware of what control solution is (62%), but only half felt it
      should be routine practice with 44% of those never recommending it. CONCLUSION:
      This study raises awareness for the need to educate patients, providers, and
      pharmacists about use of control solution to ensure glucose meter accuracy.

PMID- 28745090
TI  - If SMBG Accuracy Is Critical to Patient Safety, Why Are Inaccurate Meters Still
      on the Market?
AB  - In this issue of Journal of Diabetes Science and Technology, Christiansen and
      colleagues report results from two studies, laboratory and clinical, that
      assessed the accuracy of a new blood glucose monitoring system, the
      Contour(r)Next ONE (Ascensia Diabetes Care, Parsippany, NJ, USA). The new system
      comprises a blood glucose meter that can link (via Bluetooth(r)) to the ContourTM
      Diabetes app, which operates on a smartphone or tablet. Results from both studies
      showed that the system exceeded the accuracy standards defined by the
      International Organization for Standardization (ISO) 15197:2013. It is worrisome,
      however, that many FDA-cleared (and marketed) blood glucose monitoring systems do
      not meet ISO accuracy criteria. Significant improvements in regulatory oversight
      and enforcement are needed.

PMID- 28745091
TI  - Continuous Glucose Monitoring Use in Type 1 Diabetes: Longitudinal Analysis
      Demonstrates Meaningful Improvements in HbA1c and Reductions in Health Care
      Utilization.
AB  - BACKGROUND: Real-time continuous glucose monitoring (rtCGM) improves glycemic
      control in type 1 diabetes (T1D) patients treated with continuous subcutaneous
      insulin infusion (CSII). However, the benefits of rtCGM in T1D patients treated
      with multiple daily insulin injection (MDI) therapy has not been well studied. We
      explored the effects of rtCGM versus self-monitoring of blood glucose (SMBG) on
      clinical outcomes within a large T1D population treated with either CSII or MDI
      therapy. METHODS: This retrospective, longitudinal analysis utilized datasets
      from T1D patients enrolled in a commercial health plan to assess changes in HbA1c
      in 187 naive to rtCGM users and 6260 SMBG users. Propensity score modeling was
      used to assess inpatient admissions, emergency room (ER) visits in 1130 patients
      (565 rtCGM, 565 SMBG). Differences in HbA1c reduction (rtCGM+MDI vs rtCGM+CSII)
      were evaluated. RESULTS: Larger, clinically meaningful HbA1c reductions were seen
      among rtCGM versus SMBG users: -0.5% ( P = .004) versus -0.2% ( P < .0001); 0.3%
      diff in diff, P = .03. All-cause inpatient admissions were lower for rtCGM users:
      -42%, P = .013. Emergency room visits coded for diabetic ketoacidosis (DKA) were
      four times higher for SMBG patients than rtCGM patients: 17 versus 4, P = .0318.
      HbA1c reductions were most notable with rtCGM+MDI versus rtCGM+CSII treatment: 
      0.6% ( P = .01) versus -0.3% ( P = .16). CONCLUSIONS: Use of rtCGM in T1D
      patients facilitates greater HbA1c improvements and reduced health care system
      utilization compared with traditional SMBG use regardless of insulin
      administration method. Treatment with rtCGM in conjunction with MDI confers
      similar or greater glycemic benefits without the additional costs associated with
      CSII therapy.

PMID- 28745092
TI  - Impact of Xylose on Glucose-Dehydrogenase-Based Blood Glucose Meters for Patient
      Self-Testing.
AB  - The pentose xylose is enriched in edible algae, and is increasingly used as a
      slowly metabolized carbohydrate in functional food. It is known to interfere with
      glucose-dehydrogenase-based (GDH) blood glucose measurement systems for patients
      self-testing. The aim of our study was to investigate the extent of xylose
      interference in commercially available blood glucose meters. A heparinized whole
      blood sample was manipulated to contain 3 different glucose concentrations (50-80
      mg/dL, 130-160 mg/dL, and 250-300 mg/dL) and 4 different xylose concentrations (0
      mg/dL, 25 mg/dL, 50 mg/dL, and 100 mg/dL). Each sample was measured 3 times with
      2 different strip lots per test meter (AccuChek Aviva, AccuChek Connect, Contour
      Next, FreeStyle Freedom Lite, FreeStyle Insulinx, MyStar Extra, OneTouch Verio
      IQ, and Wellion Calla, reference: YSI GlucoStat analyzer). For analysis, we
      calculated the xylose capture rate, that is, the xylose amount wrongly displayed
      as glucose. No xylose interference was seen with 4 meters: AccuChek Aviva (mean
      capture rate 0%), AccuChek Connect (-2%), MyStar Extra (10%), and Wellion Calla
      (8%). In contrast, substantial interference was observed with Contour Next
      (100%), FreeStyle Freedom Lite (104%), FreeStyle Insulinx (120%), and OneTouch
      Verio IQ (162%). We observed xylose interference in several GDH-based meters.
      This may become important with increased use of xylose in dietary and functional
      food products, in particular in products designed for weight loss. Our findings
      may affect the meter selection for patients who are consuming such food products
      as part of their lifestyle treatment regimen.

PMID- 28745093
TI  - Optimal Use of Diabetes Devices: Clinician Perspectives on Barriers and Adherence
      to Device Use.
AB  - BACKGROUND: Insulin pumps and continuous glucose monitors (CGM) can improve
      glycemic control for individuals with type 1 diabetes (T1D). Device uptake rates
      continue to show room for improvement, and consistent adherence is needed to
      achieve better outcomes. Diabetes health care providers have important roles to
      play in promoting device use and adherence. METHODS: We surveyed 209 clinicians
      who treat people with type 1 diabetes to examine perceptions of barriers to
      device uptake, attitudes toward diabetes technology, and resources needed for
      clinicians to improve device uptake. We compared findings with our survey of
      adults with T1D. RESULTS: Younger clinicians treated more patients using insulin
      pumps ( r = -.26, P < .001) and CGM ( r = -.14, P = .02), and had more positive
      attitudes about diabetes technology ( r = -.23, P = .001). The most frequently
      endorsed modifiable barriers were perceptions that patients dislike having the
      device on their body (73% pump; 63% CGM), dislike the alarms (61% CGM), and do
      not understand what to do with device information or features (40% pump; 46%
      CGM). Clinicians wanted lower cost and better insurance coverage for their
      patients, and they recommended counseling and education to help address barriers
      and improve adherence to devices. CONCLUSION: Clinicians perceive many barriers
      to their patients initiating and adhering to diabetes devices. Findings highlight
      opportunities for intervention to improve clinician-patient communication around
      device barriers to help address them.

PMID- 28745094
TI  - NICH at Its Best for Diabetes at Its Worst: Texting Teens and Their Caregivers
      for Better Outcomes.
AB  - BACKGROUND: There is growing evidence for the feasibility of text-based
      interventions for pediatric patients with type 1 diabetes (T1D). However, less is
      known regarding whether the use of personalized text messages with high-risk
      youth and their caregivers is associated with improvements in youth health. This
      study examines the use of diabetes-specific texts and associated health outcomes
      for participants of the Novel Interventions in Children's Healthcare (NICH)
      program. METHODS: Text messages sent to youth with T1D and their caregivers
      during NICH intervention were coded regarding diabetes relevance and adherence
      related content. Health outcome data (eg, HbA1c values, hospital admissions)
      prior to and following NICH program enrollment were collected. RESULTS: Fewer
      than half (43%) of texts sent to patients and their caregivers were identified as
      being related to diabetes, and over 95% of diabetes-related texts were identified
      as adherence-related. Participants in the NICH program demonstrated a significant
      decrease in HbA1c values, t(23) = 2.78, p <= .05, and DKA-related hospital
      visits, t(24) = 2.78, p <= .01, during program involvement. Although no
      relationships were identified between patient-recipient text characteristics and
      health outcomes, the frequency and type of text messaging with caregivers was
      significantly associated with changes in health outcomes. CONCLUSIONS: This study
      represents the most extensive evaluation of diabetes-related SMS use and health
      outcomes for NICH participants to date. Findings demonstrate improvements in
      patient health during NICH program involvement. Implications include that sending
      frequent, personalized, and adherence-reinforcing texts to patients' caregivers
      may result in improved patient health, decreased utilization, and, potentially,
      associated reductions in health care costs.

PMID- 28745095
TI  - An Enhanced Model Predictive Control for the Artificial Pancreas Using a
      Confidence Index Based on Residual Analysis of Past Predictions.
AB  - BACKGROUND: Model predictive control (MPC) performance depends on the accuracy of
      the prediction model implemented by the controller. Complex physiology and
      modeling limitations often prevent the ability to provide long and accurate
      glucose predictions, which results in the need to account for prediction errors.
      METHOD: Optimal insulin dosage by Zone-MPC is calculated by solving an
      optimization problem in which a scalar index is minimized by penalizing relative
      input deviations and glucose predictions out of the reference zone. The
      controller's tuning parameters are the penalties on the input variable (insulin).
      Positive and negative relative inputs are penalized differently. A dynamic
      adaptation of the tuning parameters based on the accuracy of the model in recent
      history is implemented in this article and compared in silico to aggressive and
      conservative tunings of the same controller structure. RESULTS: Similar average
      glucose and time in the safe glucose range (70-180 mg/dL) are achieved for the
      adaptive design and traditional controller configurations. However, percentage
      time under 70 mg/dL is significantly reduced, both for announced meals using
      bolus compensation and unannounced meals with a meal detection algorithm
      triggered bolus. No differences in the average insulin delivered were observed
      between the adaptive design and the conservative or aggressive tuning for the
      bolus strategy, and the adaptive controller delivered less insulin in the other
      scenario considered. CONCLUSIONS: The adaptive strategy provides safe and
      effective glucose management as well as significant reduction of hypoglycemia
      events. No abnormal insulin delivery profiles were observed upon the application
      of the adaptive strategy.

PMID- 28745096
TI  - White Coat Adherence Occurs in Adolescents With Type 1 Diabetes Receiving
      Intervention to Improve Insulin Pump Adherence Behaviors.
AB  - BACKGROUND: To assess the occurrence of white coat adherence, defined as an
      increase in adherence to treatment regimens prior to a study appointment, in
      adolescents with type 1 diabetes (T1D) using insulin pumps and participating in a
      randomized adherence intervention trial. METHODS: Blood glucose monitoring (BGM)
      readings, carbohydrate inputs, and insulin boluses delivered were downloaded from
      the insulin pumps of adolescents, aged 10-18 years, at 3 consecutive T1D study
      visits. Linear mixed models were used to analyze patterns of BGM, carbohydrate
      inputs, and insulin boluses delivered in patients who had 40 consecutive days of
      data stored in their insulin pumps prior to the study visit. RESULTS: Stratified
      linear mixed models revealed that adolescents randomized to the Tailored Feedback
      Intervention group increased their blood glucose monitoring ( P < .01),
      carbohydrate inputs ( P < .0001), and insulin bolusing ( P < .0001) prior to
      study appointments. In contrast, white coat adherence did not occur in
      adolescents randomized to the Treatment as Usual group ( Ps > .42). CONCLUSIONS:
      White coat adherence may occur in adolescents participating in clinical trials.
      Meter and insulin pump data downloads representing the 1- to 2-week period prior
      to a study visit are likely to overestimate actual adherence during the time
      frame between study visits.

PMID- 28745097
TI  - A Mobile App for Synchronizing Glucometer Data: Impact on Adherence and Glycemic
      Control Among Youths With Type 1 Diabetes in Routine Care.
AB  - BACKGROUND: Many individuals with type 1 diabetes (T1D) upload and review blood
      glucose data between clinic visits. Mobile phone applications that receive data
      from a "connected" glucometer and that support pattern management are available
      and have the capacity to make data upload and review less burdensome. Whether
      mobile apps can improve diabetes self-management among individuals with type 1
      diabetes remains unknown. METHOD: We analyzed retrospective data on 81 youths
      with T1D who were trained to use a glucometer-connected mobile app in their self
      management. To assess the effect of glucometer synchronization ("sync") rate on
      hemoglobin A1c (HbA1c), mean blood glucose (mBG), and daily frequency of SMBG, we
      regressed those clinical outcomes on the frequency of glucometer syncs with the
      mobile app after controlling for other clinical care variables. RESULTS: Median
      age was 14.0 (IQR 10.4-15.9) years, median duration of diabetes was 4.9 (2.7,
      7.5) years, and median baseline HbA1c was 8.6% (7.9, 9.8). The sample was 49%
      male and 86% white. Youths with T1D synchronized glucometer data with the mobile
      app an average of 0.22 times per week (range 0-2.25). The glucometer sync rate
      did not have a statistically significant association with HbA1c or mean BG; in
      contrast, data sync frequency was associated with the frequency of self
      monitoring of blood glucose (SMBG) such that each additional sync was associated
      with a 2.3-fold increase in SMBG frequency ( P < .01). CONCLUSION: A glucometer
      connected mobile app may increase an individual's engagement with other aspects
      of care (eg, SMBG frequency). Whether diabetes device-connected mobile apps can
      improve glycemic control remains to be determined.

PMID- 28745098
TI  - Analysis of the Accuracy and Performance of a Continuous Glucose Monitoring
      Sensor Prototype: An In-Silico Study Using the UVA/PADOVA Type 1 Diabetes
      Simulator.
AB  - BACKGROUND: Computer simulation has been shown over the past decade to be a
      powerful tool to study the impact of medical devices characteristics on clinical
      outcomes. Specifically, in type 1 diabetes (T1D), computer simulation platforms
      have all but replaced preclinical studies and are commonly used to study the
      impact of measurement errors on glycemia. METHOD: We use complex mathematical
      models to represent the characteristics of 3 continuous glucose monitoring
      systems using previously acquired data. Leveraging these models within the
      framework of the UVa/Padova T1D simulator, we study the impact of CGM errors in 6
      simulation scenarios designed to generate a wide variety of glycemic conditions.
      Assessment of the simulated accuracy of each different CGM systems is performed
      using mean absolute relative deviation (MARD) and precision absolute relative
      deviation (PARD). We also quantify the capacity of each system to detect
      hypoglycemic events. RESULTS: The simulated Roche CGM sensor prototype (RCGM)
      outperformed the 2 alternate systems (CGM-1 & CGM-2) in accuracy (MARD = 8% vs
      11.4% vs 18%) and precision (PARD = 6.4% vs 9.4% vs 14.1%). These results held
      for all studied glucose and rate of change ranges. Moreover, it detected more
      than 90% of hypoglycemia, with a mean time lag less than 4 minutes (CGM-1: 86%/15
      min, CGM-2: 57%/24 min). CONCLUSION: The RCGM system model led to strong
      performances in these simulation studies, with higher accuracy and precision than
      alternate systems. Its characteristics placed it firmly as a strong candidate for
      CGM based therapy, and should be confirmed in large clinical studies.

PMID- 28745099
TI  - A New, Wireless-enabled Blood Glucose Monitoring System That Links to a Smart
      Mobile Device: Accuracy and User Performance Evaluation.
AB  - BACKGROUND: These studies investigated the accuracy of the new Contour(r)Next ONE
      blood glucose monitoring system (BGMS) that is designed to sync with the
      ContourTM Diabetes app on a smartphone or tablet. METHODS: A laboratory study
      tested fingertip capillary blood samples from 100 subjects in duplicate using 3
      test strip lots, based on ISO 15197:2013 Section 6.3 analytical accuracy
      standards. A clinical study assessed accuracy per ISO 15197:2013 Section 8
      criteria. Subjects with (n = 333) or without (n = 43) diabetes and who had not
      used the BGMS previously were enrolled. Each subject performed a self-test using
      the BGMS, which was repeated by a site staff member. Alternate site tests and
      venipunctures were also performed for analysis. A questionnaire was provided to
      assess user feedback on ease of use. RESULTS: In the laboratory study, 100%
      (600/600) of combined results for all 3 test strip lots met ISO 15197:2013
      Section 6.3 accuracy criteria. In the clinical study, among subjects with
      diabetes, 99.4% (327/329) of subject self-test results, 99.7% (331/332) of
      results obtained by study staff, 97.2% (309/318) of subject palm results, and
      100% (330/330) of venous results met ISO 15197:2013 Section 8 accuracy criteria.
      Moreover, 97.6% (321/329) of subject self-test results were within +/-10 mg/dl
      (+/-0.6 mmol/L) or +/-10% of the YSI reference result. Questionnaire results
      indicated that most subjects considered the system easy to use. CONCLUSIONS: The
      BGMS exceeded ISO 15197:2013 accuracy criteria in the laboratory and in a
      clinical setting.

PMID- 28745100
TI  - Patient- and Provider-Centered Design of an Outpatient Diabetes Technology
      Clinic.
AB  - The number of US patients using diabetes technology is increasing, and
      sophisticated technologies continue to emerge. Patients using diabetes technology
      require access to providers prepared to offer care in this rapidly changing
      field. The authors sought to identify factors important to both patients using
      diabetes technology and providers caring for such patients. They redesigned the
      Diabetes Technology Clinic at an academic group practice in response to the needs
      of patients and providers. Ongoing analysis of best practices, patient
      experience, and provider feedback is essential to structuring diabetes technology
      clinics to meet the complex needs of patients requiring diabetes technology. To
      our knowledge, this is the first report describing a systems engineering approach
      to develop a diabetes technology clinic.

PMID- 28745102
TI  - Inheritance and Bulked Segregant Analysis of Leaf Rust and Stem Rust Resistance
      in Durum Wheat Genotypes.
AB  - Leaf rust, caused by Puccinia triticina, and stem rust, caused by P. graminis f.
      sp. tritici, are important diseases of durum wheat. This study determined the
      inheritance and genomic locations of leaf rust resistance (Lr) genes to P.
      triticina race BBBQJ and stem rust resistance (Sr) genes to P. graminis f. sp.
      tritici race TTKSK in durum accessions. Eight leaf-rust-resistant genotypes were
      used to develop biparental populations. Accessions PI 192051 and PI 534304 were
      also resistant to P. graminis f. sp. tritici race TTKSK. The resulting progenies
      were phenotyped for leaf rust and stem rust response at seedling stage. The Lr
      and Sr genes were mapped in five populations using single-nucleotide
      polymorphisms and bulked segregant analysis. Five leaf-rust-resistant genotypes
      carried single dominant Lr genes whereas, in the remaining accessions, there was
      deviation from the expected segregation ratio of a single dominant Lr gene. Seven
      genotypes carried Lr genes different from those previously characterized in
      durum. The single dominant Lr genes in PI 209274, PI 244061, PI387263, and PI
      313096 were mapped to chromosome arms 6BS, 2BS, 6BL, and 6BS, respectively. The
      Sr gene in PI 534304 mapped to 6AL and is most likely Sr13, while the Sr gene in
      PI 192051 could be uncharacterized in durum.

PMID- 28745101
TI  - Acidosis counteracts itch tachyphylaxis to consecutive pruritogen exposure
      dependent on acid-sensing ion channel 3.
AB  - Tachyphylaxis of itch refers to a markedly reduced scratching response to
      consecutive exposures of a pruritogen, a process thought to protect against
      tissue damage by incessant scratching and to become disrupted in chronic itch.
      Here, we report that a strong stimulation of the Mas-related G-protein-coupled
      receptor C11 by its agonist, Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SL-NH2) or bovine
      adrenal medulla 8-22 peptide, via subcutaneous injection in mice induces
      tachyphylaxis to the subsequent application of SL-NH2 to the same site. Notably,
      co-application of acid and SL-NH2 following the initial injection of the
      pruritogen alone counteracted itch tachyphylaxis by augmenting the scratching
      behaviors in wild-type but not in acid-sensing ion channel 3-null, animals. Using
      an activity-dependent silencing strategy, we identified that acid-sensing ion
      channel 3-mediated itch enhancement mainly occurred via the Mas-related G-protein
      coupled receptor C11-responsive sensory neurons. Together, our results indicate
      that acid-sensing ion channel 3, activated by concomitant acid and certain
      pruritogens, constitute a novel signaling pathway that counteracts itch
      tachyphylaxis to successive pruritogenic stimulation, which likely contributes to
      chronic itch associated with tissue acidosis.

PMID- 28745103
TI  - Computer Vision for High-Throughput Quantitative Phenotyping: A Case Study of
      Grapevine Downy Mildew Sporulation and Leaf Trichomes.
AB  - Quantitative phenotyping of downy mildew sporulation is frequently used in plant
      breeding and genetic studies, as well as in studies focused on pathogen biology
      such as chemical efficacy trials. In these scenarios, phenotyping a large number
      of genotypes or treatments can be advantageous but is often limited by time and
      cost. We present a novel computational pipeline dedicated to estimating the
      percent area of downy mildew sporulation from images of inoculated grapevine leaf
      discs in a manner that is time and cost efficient. The pipeline was tested on
      images from leaf disc assay experiments involving two F1 grapevine families, one
      that had glabrous leaves (Vitis rupestris B38 * 'Horizon' [RH]) and another that
      had leaf trichomes (Horizon * V. cinerea B9 [HC]). Correlations between computer
      vision and manual visual ratings reached 0.89 in the RH family and 0.43 in the HC
      family. Additionally, we were able to use the computer vision system prior to
      sporulation to measure the percent leaf trichome area. We estimate that an
      experienced rater scoring sporulation would spend at least 90% less time using
      the computer vision system compared with the manual visual method. This will
      allow more treatments to be phenotyped in order to better understand the genetic
      architecture of downy mildew resistance and of leaf trichome density. We
      anticipate that this computer vision system will find applications in other
      pathosystems or traits where responses can be imaged with sufficient contrast
      from the background.

PMID- 28745104
TI  - pH-sensitive nanoparticles for improved oral delivery of dapsone: risk
      assessment, design, optimization and characterization.
AB  - AIM: To optimize the production of pH-sensitive dapsone (DAP) nanoparticles based
      on Eugradit L100 (NPs-EL100-DAP) for oral delivery. MATERIALS & METHODS: NPs
      EL100-DAP were optimized using a Plackett-Burman design and a Box-Behnken design.
      The physicochemical properties of the obtained nanoparticles were monitored by
      microscopy, dynamic light scattering, Fourier transform infrared spectroscopy,
      differential scanning calorimetry, in vitro release assays, and examined for
      cytotoxicity and permeation across intestinal barrier. RESULTS: The in vitro
      release assay of NPs-EL100-DAP confirmed the nanoparticles' pH sensitivity and
      the ability to deliver DAP at intestinal environment. NPs-EL100-DAP demonstrated
      enhanced intestinal interactions in comparison to free DAP, across Caco-2
      monolayers. CONCLUSION: These studies demonstrate the potential of NPs-EL100-DAP
      as a therapeutic platform for oral treatment of leprosy.

PMID- 28745105
TI  - Honey flavonoids inhibit hOATP2B1 and hOATP1A2 transporters and hOATP-mediated
      rosuvastatin cell uptake in vitro.
AB  - 1. Some flavonoids contained in the common diet have been shown to interact with
      important membrane uptake transporters, including organic anion transporting
      polypeptides (OATPs). OATP2B1 and OATP1A2 expressed in the apical membrane of
      human enterocytes may significantly contribute to the intestinal absorption of
      drugs, e.g. statins. This study is aimed at an evaluation of the inhibitory
      potency of selected food honey flavonoids (namely galangin, myricetin,
      pinocembrin, pinobanksin, chrysin and fisetin) toward hOATP2B1 and hOATP1A2 as
      well as at examining their effect on the cellular uptake of the known OATP
      substrate rosuvastatin. 2. Cell lines overexpressing the hOATP2B1 or hOATP1A2
      transporter were employed as in vitro model to determine the inhibitory potency
      of the flavonoids toward the OATPs. 3. Chrysin, galangin and pinocembrin were
      found to inhibit both hOATP2B1 and hOATP1A2 in lower or comparable concentrations
      as the known flavonoid OATP inhibitor quercetin. Galangin, chrysin and
      pinocembrin effectively inhibited rosuvastatin uptake by hOATP2B1 with IC50 ~1-10
      MUM. The inhibition of the hOATP1A2-mediated transport of rosuvastatin by these
      flavonoids was weaker. 4. The found data indicate that several of the tested
      natural compounds could potentially affect drug cellular uptake by hOATP2B1
      and/or hOATP1A2 at relative low concentrations, a finding which suggests their
      potential for food-drug interactions.

PMID- 28745106
TI  - Why Should We Use Online Research Methods? Four Doctoral Health Student
      Perspectives.
AB  - The growth of the Internet has led to an increase in researchers utilizing online
      methods. Online communities such as forums, blogs, and video platforms are
      particularly useful for research involving populations that are Internet savvy,
      seldom heard or discussing sensitive or illicit behavior. Drawing upon the
      experiences of four doctoral health students who are using online methods, this
      article discusses the value and benefits of conducting online research as well as
      the limitations and difficulties encountered. Consideration is given to the
      methodological and ethical implications of online research. Our own research
      leads us to reflect on participants' perceptions of what is public, preserving
      anonymity and protecting participants from harm.

PMID- 28745107
TI  - Effectiveness of Psychotherapy in Adult ADHD: What Do Patients Think? Results of
      the COMPAS Study.
AB  - OBJECTIVE: In the multicenter study Comparison of Methylphenidate and
      Psychotherapy in Adult ADHD (COMPAS), the efficacy of treatments has been
      primarily evaluated by observer-rated symptom change. Here, we additionally
      analyzed the patients' subjective evaluation of therapy effects. METHOD: COMPAS
      compared ADHD-specific group therapy with unspecific clinical management
      with/without concomitant pharmacotherapy in a four-armed design. Evaluation
      through the patients' retrospective perspective was performed after 1 year (post
      treatment) and after another 1.5 years (follow-up). RESULTS: In respect to
      patients' subjective ratings, ADHD-specific group psychotherapy outperformed
      unspecific management post-treatment ( z = 4.88, p < .0001) and at follow-up ( z
      = 2.90, p = .004). Rank correlations with rater-based symptom change were small
      to moderate (post-treatment: rs = 0.28, follow-up: rs = 0.16). CONCLUSION:
      Therapy evaluation based on the patients' perspective supports the concept of
      ADHD-specific group psychotherapy as a potentially useful therapy option in ADHD.

PMID- 28745108
TI  - Comparison of drug survival and clinical outcome in patients with ankylosing
      spondylitis treated with etanercept or adalimumab.
AB  - OBJECTIVE: To compare rates of drug survival and clinical response during 2 years
      of follow-up in ankylosing spondylitis (AS) patients treated with etanercept or
      adalimumab in routine care. METHOD: Biological-naive consecutive AS patients
      treated with etanercept (n = 163) or adalimumab (n = 82) were followed. Treatment
      discontinuation was due to inefficacy, adverse events, loss to follow-up,
      planning a pregnancy, or uveitis. Disease activity was assessed by the Ankylosing
      Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP). Moderate
      disease activity was defined as an ASDAS-CRP < 2.1. RESULTS: Twenty-seven
      patients (32.9%) treated with adalimumab and 30 (18.4%) with etanercept
      discontinued treatment. Cox regression analysis demonstrated a significant
      difference in survival rate between discontinuation of the drug in adalimumab
      patients compared with etanercept patients [hazard ratio (HR) 2.1, 95% confidence
      interval (CI) 1.3-4.5, p = 0.005; corrected for confounding factors: HR 2.5, 95%
      CI 1.3-4.5, p = 0.006]. There was no significant difference at 2 years of follow
      up between the adalimumab- and the etanercept-treated patients in mean +/- sd
      ASDAS-CRP (1.9 +/- 1.1 and 2.0 +/- 0.9, respectively, p = 0.624), and 23 out of
      34 (67.6%) compared to 71 out of 117 (60.7%) reached ASDAS-CRP moderate disease
      activity (odds ratio 0.738, 95% CI 0.329-1.657, p = 0.530). CONCLUSION: No
      significant difference was found between AS patients treated with etanercept and
      those treated with adalimumab in mean ASDAS-CRP and reaching ASDAS-CRP minimal
      disease activity at 2 year follow-up. Drug survival rate was higher in etanercept
      compared to adalimumab-treated patients. However, this should be interpreted
      cautiously as the risk of allocation bias cannot be excluded.

PMID- 28745109
TI  - An unusual "preexcited" cause of presyncope.

PMID- 28745110
TI  - ?

PMID- 28745111
TI  - ?

PMID- 28745112
TI  - ?

PMID- 28745113
TI  - ?

PMID- 28745114
TI  - ?

PMID- 28745115
TI  - ?

PMID- 28745116
TI  - ?

PMID- 28745117
TI  - ?

PMID- 28745118
TI  - ?

PMID- 28745119
TI  - ?

PMID- 28745120
TI  - ?

PMID- 28745121
TI  - Ineffective initiation contributes to deficient verbal and non-verbal fluency in
      patients with schizophrenia.
AB  - AIMS: Patients with schizophrenia (SCH) show impaired verbal and non-verbal
      fluency. However, these individuals' fluctuations in words or designs generation
      efficiency over time, a phenomenon that may significantly affect fluency, have
      never been studied. Thus, the aim of this research was to investigate if
      individuals with SCH may present with alternations in the dynamics of the
      information production and its control as well as to test if the potential
      abnormalities in this regard might affect these patients' overall performance on
      both verbal and non-verbal fluency tasks. METHOD: Forty-four patients with SCH
      and 40 healthy controls (HC) completed both verbal (phonological, semantic) and
      non-verbal fluency tests. To analyse processing efficiency changes over time, the
      period in which subjects had to generate words or designs (60 s) has been divided
      into 15-s sections. RESULTS: In comparison to HCs, individuals with SCH obtained
      significantly lower total scores for all fluency measures. Furthermore, group
      differences in the dynamics of the test performance also emerged, with SCH
      patients having a significantly worse production during the initial 15 s of each
      fluency task. Additionally, the initial production deficiency seen in patients
      with SCH has accounted for these individuals' total performance. Moreover,
      comparisons of errors distribution over time during the phonemic and figural
      fluency performance also revealed differences, suggesting there was a rapid
      depletion in maintaining of cognitive control in the SCH sample. CONCLUSIONS:
      Inefficient fluency in SCH may arise from a more general initiation deficits that
      may partly account for these patients' cognitive problems.

PMID- 28745122
TI  - Cell membrane-derived nanoparticles: emerging clinical opportunities for targeted
      drug delivery.
AB  - Biofunctionalization of nanoparticles (NPs) is an essential component in targeted
      drug delivery. However, current nanotechnology remains inadequate to imitate
      complex intercellular interactions existing in physiological conditions in human
      bodies. Emerging concepts have been explored to utilize human cells to generate
      cell membrane-formed NPs because cells retain inherent abilities to interact with
      human tissues compared with synthetic nanomaterials. Neutrophils, red blood cells
      (RBCs), platelets and monocytes have been employed to form therapeutic NPs to
      treat vascular disease and cancer, and these novel drug delivery platforms show
      the translation potential to improve patient quality of life. In this review, we
      will discuss the concept of cell membrane-formed NPs, the molecular mechanisms of
      their disease targeting and the potential of personalized nanomedicine.

PMID- 28745124
TI  - Dysfunction of the foetal arterial duct results in a wide spectrum of
      cardiovascular pathology.
AB  - OBJECTIVE: Foetal ductal problems may have various cardiopulmonary consequences.
      This study aimed to identify the spectrum of ductus arteriosus (DA) dysfunction
      (closure, constriction, kinking, aneurysm and thrombosis) and the resultant
      clinical and echocardiographic presentation in foetuses and neonates. METHODS AND
      RESULTS: This is a retrospective analysis of serial pre- and post-natal data of
      27 cases of foetal ductal dysfunction diagnosed at a median gestational age of 33
      weeks (range 20-39). The most common abnormalities observed were premature
      closure of the DA in 56% (15/27) and constriction in 29% (8/27). Right
      ventricular hypertrophy was present in 75% (n = 11/15) of foetuses with premature
      DA closure, while ventricular dilation (4/7, 57%) was a more common feature in
      foetuses with ductal constriction. After birth, 63% (17/27) of new borns
      presented with cyanosis and pulmonary hypertension that required active
      treatment. Three infants died after birth. Abnormalities resolved spontaneously
      after birth in about 50% of patients. In some children, pulmonary valve stenosis
      and regurgitation was progressive and required further treatment. CONCLUSIONS: An
      abnormal right heart on foetal four-chamber ultrasound view should alert the
      sonographer to the possible presence of foetal ductal dysfunction. Ductal
      occlusion, transient or fixed constriction, kinking and aneurysm formation are
      associated with foetal cardiopulmonary sequelae. Symptoms and pathology is
      probably related to the type, foetal age, rapidity of progression and duration of
      intrauterine ductal dysfunction. Correspondingly, clinical outcomes vary ranging
      from little or no symptoms to severe respiratory distress and even foetal or
      neonatal death.

PMID- 28745125
TI  - A fulminant case of idiopathic giant cell myocarditis.

PMID- 28745123
TI  - iRGD-functionalized PEGylated nanoparticles for enhanced colon tumor accumulation
      and targeted drug delivery.
AB  - AIM: To enhance the tumor accumulation and targeted drug delivery for colon
      cancer therapy, iRGD peptide was introduced to the surface of PEGylated
      camptothecin-loaded nanoparticles (NPs). METHODS: Cellular uptake, targeting
      specificity, biodistribution and antitumor capacity were evaluated. RESULTS: The
      functionalization of iRGD facilitated tumor accumulation and cellular uptake of
      NPs by Colon-26 cells. Furthermore, the resultant iRGD-PEG-NPs remarkably
      improved the therapeutic efficacy of camptothecin in vitro and in vivo by
      inducing a higher degree of tumor cell apoptosis compared with PEG-NPs.
      CONCLUSION: iRGD-PEG-NP is a desired drug delivery system to facilitate the drug
      accumulation in orthotopic colon tumor tissues and further drug internalization
      by colon cancer cells.

PMID- 28745126
TI  - An unusual cause of cardiac tamponade following pericardial window formation.

PMID- 28745127
TI  - Modified gold-based siRNA nanotherapeutics for targeted therapy of triple
      negative breast cancer.
AB  - AIM: In this study, we aimed to therapeutically target eukaryotic elongation
      factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor
      model. MATERIALS & METHODS: We synthesized a highly monodisperse nanoformulation
      using polyethylenimine-modified gold nanoparticles (AuNP-PEI) as siRNA delivery
      vehicle and evaluated gene downregulation. RESULTS: We found that AuNP-PEI/eEF-2K
      nanoformulation was highly effective for in vitro and in vivo gene downregulation
      and showed remarkable antitumor efficacy that was associated with eEF-2K
      knockdown, inhibition of Src and MAPK-ERK signaling pathways in a TNBC orthotopic
      tumor model. CONCLUSION: Our study suggests that eEF-2K plays an important role
      in TNBC tumorigenesis and its inhibition by AuNP-PEI/eEF-2K siRNA-based
      nanotherapeutics may be a potential therapeutic strategy for TNBC.

PMID- 28745128
TI  - The permeability characteristics and interaction of main components from Si-Ni
      San in a MDCK epithelial cell monolayer model.
AB  - 1. Si-Ni-San (SNS) possesses extensive therapeutic effects, however, the extent
      to which main components are absorbed and the mechanisms involved are
      controversial. 2. In this study, MDCK cell model was used to determine the
      permeability characteristics and interaction between the major components of Si
      Ni-San, including saikosaponin a, paeoniflorin, naringin and glycyrrhizic acid.
      3. The transport of the major components was concentration-dependent in both
      directions. Moreover, the transport of paeoniflorin, naringin and glycyrrhizic
      acid was significantly reduced at 4 degrees C or in the presence of NaN3.
      Additionally, the efflux of paeoniflorin and naringin were apparently reduced in
      the presence of P-gp inhibitor verapamil. The transport of glycyrrhizic acid was
      clearly inhibited by the inhibitors of MRP2, indicating that MRP2 may be involved
      in the transport of glycyrrhizic acid. However, the results indicated that
      saikosaponin a was absorbed mainly by passive diffusion. Furthermore, the
      combined incubation of four major components had a powerful sorbefacient effect
      than a single drug used alone which may be regulated by tight junctions. 4. Taken
      together, our study provides useful information for pharmacological applications
      of Si-Ni-San and offers new insights into this ancient decoction for further
      researches, especially in drug synergism.

PMID- 28745130
TI  - Longitudinal Association Between Subjective Fatigue and Future Falls in Community
      Dwelling Older Adults: The Locomotive Syndrome and Health Outcomes in the Aizu
      Cohort Study (LOHAS).
AB  - OBJECTIVE: We examined the longitudinal association between the severity of
      fatigue and falls in community-dwelling older adults. METHOD: Subjective fatigue
      was assessed using the Short Form 36 Health Survey (SF-36) Vitality subscale and
      classified into four categories by quartile (mildest, mild, moderate, severe).
      The main outcome was the incidence of any falls during the 2-year follow-up
      period. RESULTS: Of the 751 participants, 236 (31.4%) experienced falls during
      the 2-year period. In multivariable logistic regression analysis with adjustment
      for possible confounding factors, the adjusted odds ratios (and 95% confidence
      intervals) for mild, moderate, and severe categories (vs. mildest category) of
      1.60 (0.94-2.75), 1.87 (1.12-3.11), and 2.15 (1.23-3.76), respectively ( p for
      trend = .007). DISCUSSION: Our results suggest that the severity of fatigue is
      associated with the risk of subsequent falls for community-dwelling older adults
      even after adjustment for possible confounding factors.

PMID- 28745129
TI  - Complex effects of tumor microenvironment on the tumor disposition of carrier
      mediated agents.
AB  - Major advances in carrier-mediated agents, including nanoparticle, conjugates and
      antibody-drug conjugates, have created revolutionary drug delivery systems in
      cancer over the past two decades. While these agents provide several advantages,
      such as greater duration of exposure and solubility, compared with their small
      molecule counterparts, there is substantial variability in delivery of these
      agents to tissues and especially tumors. This review provides an overview of
      tumor microenvironment factors that affect the pharmacokinetics and
      pharmacodynamics of carrier-mediated agents observed in preclinical models and
      patients.

PMID- 28745132
TI  - Joint incorporation of randomised and observational evidence in estimating
      treatment effects.
AB  - In evidence-based medicine, randomised trials are regarded as a gold standard in
      estimating relative treatment effects. Nevertheless, a potential gain in
      precision is forfeited by ignoring observational evidence. We describe a simple
      estimator that combines treatment estimates from randomised and observational
      data and investigate its properties by simulation. We show that a substantial
      gain in estimation accuracy, compared with the estimator based solely on the
      randomised trial, is possible when the observational evidence has low bias and
      standard error. In the contrasting scenario where the observational evidence is
      inaccurate, the estimator automatically discounts its contribution to the
      estimated treatment effect. Meta-analysis extensions, combining estimators from
      multiple observational studies and randomised trials, are also explored.

PMID- 28745131
TI  - The effects of a home-based physical activity intervention on cardiorespiratory
      fitness in breast cancer survivors; a randomised controlled trial.
AB  - The aim of this current randomised controlled trial was to evaluate the effects
      of a home-based physical activity (PA) intervention on cardiorespiratory fitness
      in breast cancer survivors. Thirty-two post-adjuvant therapy breast cancer
      survivors (age = 52 +/- 10 years; BMI = 27.2 +/- 4.4 kg?m2) were randomised to a
      six-month home-based PA intervention with face-to-face and telephone PA
      counselling or usual care. Cardiorespiratory fitness and self-reported PA were
      assessed at baseline and at six-months. Participants had a mean relative VO2max
      of 25.3 +/- 4.7 ml?kg-1?min-1, which is categorised as "poor" according to age
      and gender matched normative values. Magnitude-based inference analyses revealed
      likely at least small beneficial effects (effect sizes >=.20) on absolute and
      relative VO2 max (d = .44 and .40, respectively), and total and moderate PA (d =
      .73 and .59, respectively) in the intervention compared to the usual care group.
      We found no likely beneficial improvements in any other outcome. Our home-based
      PA intervention led to likely beneficial, albeit modest, increases in
      cardiorespiratory fitness and self-reported PA in breast cancer survivors. This
      intervention has the potential for widespread implementation and adoption, which
      could considerably impact on post-treatment recovery in this population.

PMID- 28745133
TI  - Bioprosthetic mitral valve thrombosis: complete resolution by anticoagulation.

PMID- 28745134
TI  - Giant left circumflex coronary artery aneurysm with fistula to the right atrium.
AB  - Coronary artery fistulae are rare cardiac anomalies with a prevalence of 0.2% of
      all the patients undergoing coronary angiography. The majority of them are
      congenital and generally origin from the right coronary artery. Occasionally
      acquired (mostly iatrogenic) fistulae can develop. Although frequently
      subclinical, symptoms of angina and congestive heart failure may occur. We
      present an unusual well-illustrated case of a strongly dilated circumflex
      coronary artery with formation of two giant aneurysms and fistulous communication
      towards the right atrium.

PMID- 28745135
TI  - A rare emboligenic origin of ischaemic stroke.

PMID- 28745136
TI  - Different CKD aetiologies and duration of ACE inhibitor/ARB use can also affect
      left ventricular functions.

PMID- 28745137
TI  - Exploring the Value Proposition of Primary Care for Safety-Net Patients Who
      Utilize Emergency Departments to Address Unmet Needs.
AB  - BACKGROUND: An underlying assumption of strategies intended to promote
      appropriate primary care over emergency department (ED) use for ongoing health
      care needs is that patients will understand the "value proposition" of primary
      care: that they will receive specific benefits from primary care providers over
      and above what they receive from EDs. However, there is evidence that this value
      proposition may be unclear to safety-net patients. The goals of this study are to
      describe factors motivating ED use for low-acuity conditions; describe
      similarities and differences in usual source of care (USOC) experiences, by ED
      versus non-ED setting; and assess awareness and perceptions of the patient
      centered medical home (PCMH) concept among safety-net patients. METHODS: We
      conducted a cross-sectional descriptive study of adult patients (n = 329) at 3
      safety-net hospitals in the Southwest. RESULTS: Key reasons for ED use were
      perceived urgency, lack of awareness about other options for care, payment
      flexibility, and perceived quality and convenience. Approximately half of
      participants indicated they would seek treatment in non-ED settings, if
      available, but agreement differed by group (non-ED USOC, 60.2%; ED USOC, 50.7%;
      no USOC, 45.3%; P = .025). Agreement that providers coordinated access to needed
      medical services was significantly higher among patients with non-ED USOCs;
      agreement that providers coordinated non-medical services that facilitate access
      to care was similar (approximately 45%) for patients with ED and non-ED USOCs.
      Approximately 70% of participants in both groups agreed that every person should
      have a medical home. CONCLUSIONS: Perceived experiences of care in ED and non-ED
      USOC settings suggest challenges and opportunities for increasing the value
      proposition of primary care for safety-net patients. Although patients are
      receptive to the PCMH concept, effective strategies to better highlight the value
      of primary care in coordinating both medical and related nonmedical services and
      other PCMH benefits warrant further investigation.

PMID- 28745138
TI  - Fluid mud consolidation delayed by extracellular polymer substances.
AB  - A strain of bacterium identified as Burkholderia vietnamiensis was newly isolated
      and screened from mud deposited in a harbour basin. The effects of B.
      vietnamiensis on the fluid mud consolidation and the extracellular polymer
      substances (EPS) secreted by the microorganisms were examined in laboratory
      experiments. The experiments revealed the important characteristics of the EPS
      and their critical contents for nautical-depth applications. The self-weight
      consolidations in the settling and permeability regimes were best predicated by
      an exponential equation and a logarithmic equation, respectively. EPS cannot
      change the trend of sediment settling and consolidation, but its content is
      negatively correlated with the velocity of sediment consolidation. EPS with high
      polysaccharide/protein ratio is a potential reference to select bacteria for
      nautical-depth applications. The critical EPS content that would effectively
      extend the usage time of nautical depths was estimated as 2.34 g/l.

PMID- 28745139
TI  - Role of miR-29 as marker of risk of acute rejection after heart transplant.
AB  - BACKGROUND: Circulating miRNAs are potential biomarkers of the pathogenesis of
      certain diseases and in monitoring therapeutic responses. We hypothesized that
      serum miR-29 can determine risk of acute cardiac allograft rejection. METHODS:
      Peripheral vein blood was collected from 50 healthy volunteers and 506 patients
      during post-transplant surveillance. Serum cardiac troponin I (cTnI) and miR-29
      was detected by ELISA and qRT-PCR assay respectively. Rejection risk was defined
      as International Society of Heart and Lung Transplant score from leukocyte
      infiltration of an endomyocardial biopsy. No evidence of rejection was defined as
      grade R0, mild as R1, moderate as 2R and severe as 3R. Specificity and
      sensitivity of miR-29 to discriminate rejection was determined by the area under
      the curve (AUC) of receiver operating characteristic curve analysis. Correlations
      between miR29 and rejection grade were compared. RESULTS: Serum miR-29 was 100.8
      +/- 42.4 copies/MUl in R0 groups (P = 0.164 versus controls), 537.5 +/- 84.3
      copies/MUl in R1 groups (P = 0.024) and 1478.4 +/- 198.7 copies/MUl in the joint
      R2/R3 groups (P = 0.001). MiR-29 was 1963.5 +/- 214.7 six months after
      transplantation, 1242.5 +/- 103.8 after a year, 825.6 +/- 58.2 after 2 years,
      413.8 +/- 61.9 after 3 years and 270.6 +/- 34.6 ng/mL after 4 years (P < 0.001).
      The level of miR-29 correlated positively with cTnI, NT-proBNP, white blood cell
      counts, and negatively with lymphocyte counts (all P < 0.001). The AUC values
      (95% CI) for discriminating R0 and R1 was 0.81 (0.75-0.89), and was 0.79 (0.72
      0.86) for R0 and R2/R3 (both P < 0.01). CONCLUSION: miR-29 is a promising
      predictor of the risk of heart transplant rejection.

PMID- 28745140
TI  - Effect of CuO nanoparticles on ammonia removal and EPS secretion of CANON sludge
      in the presence of nitrite suppression.
AB  - Completely autotrophic nitrogen removal over nitrite (CANON) process was an
      innovative technology for nitrogen removal from wastewater. It is necessary to
      clear the impact of CuO nanoparticles (CuO NPs) on CANON process since the
      widespread utilize increased their opportunity for entering into wastewater. In
      this study, the short-term and long-term effects of CuO NPs on the ammonia
      removal and extracellular polymeric substance (EPS) secretion were analyzed in
      the presence of nitrite, with the CuO NPs of 0, 5, 10, 20, 50, 100, 200, and 500
      mg L-1, respectively. Results suggested that low concentration of CuO NPs could
      enhance the ammonia removal. The inhibition threshold of CuO NPs on CANON sludge
      within short-term exposure was 20 mg L-1, while that of long-term exposure was 10
      mg L-1. Both short-term and long-term exposure within CuO NPs significantly
      impacted the ammonia removal, and both the nitrite and CuO NPs influenced the EPS
      secretion.

PMID- 28745141
TI  - Comparison of the long-term reproducibility of the walk test and of exercise peak
      oxygen consumption in patients with preserved exercise capacity.
AB  - : Short-term and long-term reproducibility of the cardiopulmonary (CPX) exercise
      test have been established. Though short and mid-term reproducibility of the walk
      test has been ascertained, this was not extensively done for the long-term
      reproducibility. The aim of the study was to examine the long-term
      reproducibility of distance walked in an allotted time and to check the stability
      of the relationship between walked distance and exercise peak VO2 (pVO2).
      METHODS: Forty six subjects (33 men; 57 +/- 14 years), referred for functional
      capacity assessment, were studied twice by CPX and walking test. On the same day,
      CPX was performed on a bicycle or a treadmill and walk test in a corridor as
      required by specific guidelines. We performed a 12-minute walk test and the
      distance covered in six minutes was systematically taken down. A free time
      interval of 1.5 hours was observed between the exercise tests. Distance walked in
      the allotted time and pVO2 were analysed. Reproducibility was assessed according
      to Bland and Altman plots and intra-class coefficient correlation (ICC). The
      relationship between distance ambulated and pVO2 was analysed by the Spearman
      coefficient correlation. RESULTS: The time interval between the two evaluations
      was 290 +/- 10 days. During this meantime, for those subjects having drug
      treatment, no change was recorded in their regimen. BMI remained stable for the
      entire studied population (28 +/- 5 kg/m2). Minute walked distance was
      respectively 522 +/- 83 and 527 +/- 76 m in six minutes, 1033 +/- 182 and 1041 +/
      153 m in 12 minutes. pVO2 was 21 +/- 7 and 22 +/- 7 ml/kg/min (all p = NS). The
      walk test was reproducible in the long-term, regardless of the modality (6 or 12
      minute walk) as shown by the Bland-Altman plots and the high ICC of .89.
      Spearman's rho coefficient between distance ambulated and pVO2 was modest and
      remained stable over time whatever the allotted time: Spearman's r = .54; p =
      .0011 (1st evaluation) and Spearman's r = .51; p = .0019 (2nd evaluation) between
      6-minute distance walked and pVO2. CONCLUSIONS: The walking distance in an
      allotted time seems highly reproducible in the long-term. Its relationship with
      pVO2 remains stable over time. It could be of value for repeated assessment of
      patients' exercise capacity in a first step. Further evaluation in a larger
      population is needed to confirm our result and its usefulness in clinical
      practice.

PMID- 28745142
TI  - Pharmacological effects of protocatechuic acid and its therapeutic potential in
      neurodegenerative diseases: Review on the basis of in vitro and in vivo studies
      in rodents and humans.
AB  - Protocatechuic acid has very promising properties potentially useful in the
      inhibition of neurodegenerative diseases progression. It is the main metabolite
      of the complex polyphenolic compounds and is believed to be responsible for
      beneficial effects associated with consumption of the food products rich in
      polyphenols. Protocatechuic acid is present in the circulation significantly
      longer and at higher concentrations than parent compounds and easily crosses the
      blood brain barrier. The aim of the following paper is to provide an extensive
      and actual report on protocatechuic acid and its pharmacological potential in
      prevention and/or treatment of neurodegenerative diseases in humans based on
      existing data from both in vitro and in vivo studies. Experimental studies
      strongly support the role of protocatechuic acid in the prevention of
      neurodegenerative processes, including Alzheimer's and Parkinson's diseases, due
      to its favorable influence on processes underlying cognitive and behavioral
      impairment, namely accumulation of the beta-amyloid plaques in brain tissues,
      hyperphosphorylation of tau protein in neurons, excessive formation of reactive
      oxygen species and neuroinflammation. There is a growing evidence that
      protocatechuic acid may become in the future efficacious and safe substance that
      protects against neurodegenerative disorders.

PMID- 28745143
TI  - High-fat simple carbohydrate (HFSC) diet impairs hypothalamic and corpus striatal
      serotonergic metabolic pathway in metabolic syndrome (MetS) induced C57BL/6J
      mice.
AB  - OBJECTIVES: To study the effect of specially formulated high-fat simple
      carbohydrate diet (HFSC) on the serotonin metabolic pathway in male C57BL/6J
      mice. METHODS: Previous studies from our laboratory have shown that specially
      formulated HFSC induces metabolic syndrome in C57BL/6J mice. In the present
      investigation, 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid were
      analyzed in two brain regions (hypothalamus, corpus striatum), urine and plasma
      of HFSC-fed mice on a monthly basis up to 5 months using high-performance liquid
      chromatography fitted with electrochemical detector. The data were analyzed using
      Graph pad Prism v7.3 by two-way ANOVA and post hoc Tukey's test (to assess the
      effect of time on the serotonergic metabolic pathway). RESULTS: HFSC feed was
      observed to lower the hypothalamic serotonergic tone as compared to the age
      matched control-fed C57BL/6J mice. Although the hypothalamic serotonergic tone
      was unaltered over time due to consumption of diet per se, hypothalamic 5-HTP
      levels were observed to be lower on consumption of HFSC feed over duration of 5
      months as compared to 1st month of consumption of HFSC feed. The striatal 5-HTP
      levels were lowered in the HFSC-fed mice after 4 months of feeding as compared to
      the age-matched control-fed mice. The striatal 5-HTP levels were also lower in
      both control and HFSC-fed mice due to consumption of the respective diet over a
      duration of 5 months. Increased plasma 5-HTP levels were observed due to
      consumption of HFSC feed over duration of 5 months in the HFSC-fed group.
      However, higher breakdown of serotonin was observed in both the plasma and urine
      of HFSC-fed C57BL/6J mice as per the turnover studies. DISCUSSION: The central
      and peripheral serotonergic pathway is affected differentially by both the type
      of diet consumed and the duration for which the diet is consumed. The
      hypothalamic, striatal and plasma serotonergic pathway were altered both by the
      type of feed consumed and the duration of feeding. The urine serotonergic pathway
      was affected by mainly the duration for which a particular diet was consumed.
      These findings may have implications in the feeding behavior, cognitive decline
      and depression associated with metabolic syndrome patients.

PMID- 28745144
TI  - Relative resistance index (RRI) - a scoring system for antibiotic resistance in
      Pseudomonas aeruginosa.
AB  - BACKGROUND: There is a need to measure antibiotic resistance of Pseudomonas
      aeruginosa (PA) in cystic fibrosis (CF), either qualitatively or quantitatively,
      to inform patient management. The aim of this study was to develop a simple
      method by which resistance can be quantified by calculating a relative resistance
      index (RRI), and to assess correlation of RRIs with clinical variables. METHODS:
      In our model, RRIs were calculated based on resistance to aztreonam, ceftazidime,
      ciprofloxacin, colistin, meropenem, tazocin, temicillin and tobramycin. Eighty
      five adults with CF and chronic PA colonisation were identified. For each, all PA
      cultures were allocated a score of 0 for susceptible, 0.5 for intermediate
      resistance or 1 for resistance for each antibiotic listed above, and the RRI
      calculated by dividing the sum of these by the number of antibiotics, giving a
      maximum score of 1. The mean RRIs for all cultures were correlated with key
      clinical variables monitored in CF patients (including age, FEV1, IV antibiotic
      days and BMI). RESULTS: RRIs for non-mucoid PA exhibited moderate positive
      correlation with total number of IV days (r = 0.405; p < 0.001) and moderate
      negative correlation with FEV1 % predicted (r = -0.437; p < 0.001). RRIs were not
      significantly correlated with duration of colonisation, typing (clonal vs other
      strain) or BMI. Median RRIs were significantly higher for females (0.26, IQR 0.13
      0.54) than males (0.18, IQR 0.07-0.37) for non-mucoid PA only (p = 0.03).
      CONCLUSIONS: RRI is an easily calculated measure that correlates with other
      clinical variables in CF patients and enables quantitative monitoring of
      resistance.

PMID- 28745145
TI  - Magnetic Compression Stricturoplasty For Treatment of Refractory Esophageal
      Strictures in Children: Technique and Lessons Learned.
AB  - INTRODUCTION: Esophageal stricture is the most common complication following
      repair of esophageal atresia (EA). In general, these strictures are successfully
      managed using endoscopic techniques including bougie and balloon dilation,
      stenting, and chemotherapeutic agent application. If these techniques are
      unsuccessful, patients require segmental esophageal resection and reanastomosis
      or esophageal replacement. Magnetic compression anastomosis has been described in
      children. Herein we report our experience with magnetic compression
      stricturoplasty to treat refractory strictures after EA repair. METHODS: We
      reviewed our experience using magnets to treat refractory strictures in 2
      patients. Both patients failed multiple standard interventions. Because of near
      complete esophageal obstruction, both patients were candidates for esophageal
      replacement or segmental resection/anastamosis. In both patients, we applied
      neodymium-iron-boron magnets using fluoroscopic and endoscopic guidance. RESULTS:
      The magnets were successfully positioned in both cases. Magnets were left in
      place for 7 and 10 days allowing for gradual compression
      stricturoplasty/anastamosis. Upon removal of the magnets, recanalization was
      visualized endoscopically and self-expanding stents were placed. There were no
      leaks or significant early complications. By 31 months post-magnetic
      stricturoplasty, both patients achieved durable esophageal patency without
      dysphagia. CONCLUSION: Magnetic stricturoplasty was successful at establishing
      early patency of the esophagus in 2 patients with recalcitrant EA strictures.
      Fundamental knowledge of magnetism was critical in configuring magnet arrays for
      surgery. In both cases, early follow-up is promising. Further follow-up will
      define the long-term success of this technique.

PMID- 28745147
TI  - Early Birds by Light at Night: Effects of Light Color and Intensity on Daily
      Activity Patterns in Blue Tits.
AB  - Artificial light at night disturbs the daily rhythms of many organisms. To what
      extent this disturbance depends on the intensity and spectral composition of
      light remain obscure. Here, we measured daily activity patterns of captive blue
      tits ( Cyanistes caeruleus) exposed to similar intensities of green, red, or
      white light at night. Birds advanced their onset of activity in the morning under
      all light colors but more under red and white light than under green light.
      Offset of activity was slightly delayed in all light colors. The total activity
      over a 24-h period did not change but birds moved a part of their daily activity
      into the night. Since the effect of red and white lights are comparable, we
      tested the influence of light intensity in a follow-up experiment, where we
      compared the activity of the birds under different intensities of green and white
      light only. While in the higher range of intensities, the effects of white and
      green light were comparable; at lower intensities, green light had a less
      disturbing effect as compared with white light on daily rhythms in blue tits. Our
      results show that the extent of this disturbance can be mitigated by modulating
      the spectral characteristics and intensity of outdoor lighting, which is now
      feasible through the use of LED lighting.

PMID- 28745148
TI  - Special Issue on biopsychosocial perspectives on the menopause.

PMID- 28745146
TI  - Disorganized attachment in infancy: a review of the phenomenon and its
      implications for clinicians and policy-makers.
AB  - Disorganized/Disoriented (D) attachment has seen widespread interest from policy
      makers, practitioners, and clinicians in recent years. However, some of this
      interest seems to have been based on some false assumptions that (1) attachment
      measures can be used as definitive assessments of the individual in
      forensic/child protection settings and that disorganized attachment (2) reliably
      indicates child maltreatment, (3) is a strong predictor of pathology, and (4)
      represents a fixed or static "trait" of the child, impervious to development or
      help. This paper summarizes the evidence showing that these four assumptions are
      false and misleading. The paper reviews what is known about disorganized infant
      attachment and clarifies the implications of the classification for clinical and
      welfare practice with children. In particular, the difference between
      disorganized attachment and attachment disorder is examined, and a strong case is
      made for the value of attachment theory for supportive work with families and for
      the development and evaluation of evidence-based caregiving interventions.

PMID- 28745149
TI  - Antenatal support for obese women cuts complication risk.
AB  - Antenatal clinics for severely obese pregnant women can cut pregnancy
      complications.

PMID- 28745150
TI  - Device offers fast measurement of immune system response in sepsis.
AB  - A new portable device can rapidly find markers of a life-threatening sepsis
      infection from a single drop of blood.

PMID- 28745151
TI  - New guidance on oxygen use in adults.
AB  - Essential facts The 2015 British Thoracic Society (BTS) emergency oxygen audit
      report found one in seven of the 55,000 patients in UK hospitals at the time of
      the audit received oxygen therapy for their condition. Of these, 40% were
      receiving oxygen without a prescription or written order.

PMID- 28745152
TI  - Get ready for revalidation.
AB  - Revalidation study days are taking place across the UK throughout 2017. As well
      as offering nurses and midwives the opportunity to discuss their individual
      concerns with revalidation experts, they enable attendees to complete part of
      their revalidation.

PMID- 28745153
TI  - Health education is key to all I do.
AB  - Staff nurse Anne Thomas won the RCNi Nurse Awards community category for her
      health promotion outreach work supporting men in her rural community. She trained
      as a nurse and midwife in south London in the early 1980s. Moving to north Wales
      in 1985, she worked on Dolgellau Hospital's medical ward before becoming a
      district nursing and community midwifery sister. Anne went to Dolgellau's
      midwifery unit in 1992 but was transferred to her current role in outpatients in
      1998 following an epilepsy diagnosis.

PMID- 28745154
TI  - Using telehealth in the management of hypertension.
AB  - Telehealth is a recent concept in hypertension management, and involves using
      electronic technology to monitor patients' vital signs, such as blood pressure,
      in their homes. This article presents the findings of a literature review that
      explored the issues associated with implementing telehealth in the primary care
      setting. It outlines the challenges associated with telehealth, as well as the
      potential benefits in terms of improving hypertension management. Aim To explore
      the usefulness of, and evidence for, telehealth in the management of hypertension
      in the primary care setting. Method The population, intervention, comparison and
      outcome (PICO) tool was used to define the research question for the literature
      review, which was: 'Do adults with hypertension being monitored with
      telehealth/telemonitoring have a higher quality of life and improved management
      compared with standard care?' Findings The literature review identified that a
      common challenge in implementing telehealth in patients with hypertension was the
      requirement to improve patients' compliance with and participation in telehealth
      systems. Conclusion Ongoing challenges with the implementation of telehealth
      include suboptimal feedback, and reduced patient interest in and compliance with
      telehealth systems. It was also noted that patients involved in longer trials had
      a higher withdrawal rate than those enrolled on shorter intense studies. In
      addition, patient lifestyle choices, including outdoor working, and lack of Wi-Fi
      proved a challenge to self-monitoring. If not resolved, such challenges could
      adversely affect the widespread use of telehealth.

PMID- 28745155
TI  - Single dose intravenous paracetamol or intravenous propacetamol for postoperative
      pain.
AB  - statement The mission of the Cochrane Nursing Care Field (CNCF) is to improve
      health outcomes through increasing the use of the Cochrane Library and supporting
      Cochrane's role by providing an evidence base for nurses and healthcare
      professionals who deliver, lead or research nursing care. The CNCF produces
      Cochrane Corner columns, summaries of recent nursing-care-relevant Cochrane
      Reviews that are regularly published in collaborating nursing-related journals.
      Information on the processes CNCF has developed can be accessed at:
      cncf.cochrane.org/evidence-transfer-program-review-summaries . This is a Cochrane
      review summary of: McNicol ED, Ferguson MC, Haroutounian S et al (2016) Single
      dose intravenous propacetamol or intravenous paracetamol for postoperative pain.
      Cochrane Database of Systematic Reviews. Issue 10. CD007126. doi:
      10.1002/14651858.CD007126.pub3.

PMID- 28745156
TI  - Recognising and diagnosing depression in children and young people.
AB  - This article focuses on the recognition and diagnosis of depression in children
      and young people. Depression in children and young people is underdiagnosed and
      has been linked to long-term harm. Effective recognition of the condition is
      crucial in reducing its burden, and supports appropriate management to prevent
      potential long-term harm. This article explores the causes, risk factors, and
      signs and symptoms of depression in children and young people, and the role of
      nurses and other healthcare practitioners in identifying the condition in this
      patient group.

PMID- 28745157
TI  - Exceptional nurse saved my life after mental health diagnosis.
AB  - When I first met Karen Coutts at a mental health inpatient unit in Lancashire, I
      was at the lowest point of my life, having been diagnosed with dissociative
      identity disorder.

PMID- 28745159
TI  - Pilot programme eases transition to nursing for staff trained overseas.
AB  - A university is offering London NHS trusts the opportunity to 'tap into the
      unrecognised talent' of nurses trained overseas by running a course designed to
      help them work as nurses in the UK.

PMID- 28745160
TI  - Student life - Prospect of police interview daunted me, but was my duty.
AB  - I was involved in an investigation of the death of a patient following a
      medication error.

PMID- 28745161
TI  - NHS homes fund could offer a glimmer of hope.
AB  - Buried in the recent avalanche of negative news about nursing shortages and
      Brexit is a glimmer of hope - perhaps. The NHS Confederation has floated the idea
      of setting up a L10 billion NHS homes fund to enable the health service to
      provide staff housing.

PMID- 28745162
TI  - Ministers call on NHS employers to boost stop-smoking support for staff.
AB  - NHS staff who smoke will be given more support to quit under government plans to
      cut smoking rates in England.

PMID- 28745163
TI  - When parents no longer trust the professionals.
AB  - Away from the media spotlight, nurses in neonatal and intensive care units across
      the UK continue to do their jobs. Difficult ethical cases in these units, such as
      the one at the centre of the High Court challenge by the parents of baby Charlie
      Gard (pictured), are more common than people might think.

PMID- 28745164
TI  - There are so many reasons to be proud of our nursing workforce.
AB  - Nursing and midwifery staff provide highly skilled and compassionate care, which
      I see on visits to front-line services. I remain immensely proud of what we do
      for those we care for.

PMID- 28745166
TI  - Register suspension for 'sickness' scam.
AB  - A nurse team leader whose role included investigating sick leave was suspended
      from the register for claiming sick pay while working.

PMID- 28745169
TI  - Specialties valued.
AB  - In your article on the NMC education consultation (feature, 12 July), Dame June
      Clark says 'nurses who support premature specialisation are not patient-centred -
      their selfish aim is to protect their specialty'.

PMID- 28745170
TI  - Regulator reveals reasons registrants face FtP panels.
AB  - Fewer than one in five referrals to fitness to practise proceedings concern
      patient care, the Nursing and Midwifery Council has revealed.

PMID- 28745171
TI  - Neutropenic sepsis.
AB  - What was the nature of the CPD activity, practice-related feedback and/or event
      and/or experience in your practice? The article discussed the prevention,
      identification and treatment of neutropenic sepsis, which is a potentially life
      threatening complication of chemotherapy.

PMID- 28745172
TI  - Gambling with standards.
AB  - A year ago I predicted that applications to nursing degrees would fall, and they
      have. Meanwhile, the government, universities and the Council of Deans of Health
      rush headlong into implementing the associate nurse role - a role that may
      undermine the prospects of registered nurses, as employers choose the cheaper
      salary of the associate nurse.

PMID- 28745173
TI  - Hospital parking.
AB  - Nurses are among staff at the University Hospital of Wales in Cardiff who were
      'devastated' by a court ruling over parking fines that has left many owing
      hundreds of pounds.

PMID- 28745177
TI  - Assisted dying debate highlights need to prioritise palliative care.
AB  - Nurse Alison Pickard's experience makes for difficult reading. She has been
      diagnosed with motor neurone disease (MND) and gave evidence in support of a
      change to the law on assisted dying in a High Court case in London.

PMID- 28745175
TI  - Put weight in perspective.
AB  - Your readers' panel question (19 July) asked 'should weight problems be raised in
      a nurse's appraisal?'.

PMID- 28745178
TI  - Managing and Leading in Inter-agency Settings (second edition) Dickinson Helen
      and Carey Gemma Managing and Leading in Inter-agency Settings (second edition)
      304pp L12.99 Policy Press 9781447329848 1447329848 [Formula: see text].
AB  - In a climate of national and international health and social care reform, there
      is increased emphasis on the role of partnership working across public, private
      and third-sector services.

PMID- 28745179
TI  - Nurse backs challenge to law on assisted dying.
AB  - When Alison Pickard was diagnosed with motor neurone disease (MND), she had
      established a nursing career that spanned five decades. Now, more than five years
      on from her diagnosis, she has given written evidence backing a High Court bid to
      challenge current legislation and make assisted dying legal.

PMID- 28745180
TI  - Aromatherapy, Massage and Relaxation in Cancer Care Carter Ann and Mackereth
      Peter A (Eds) Aromatherapy, Massage and Relaxation in Cancer Care 232pp L25
      Singing Dragon 9781848192812 1848192819 [Formula: see text].
AB  - As a devotee of complementary therapies, I loved this book. It offers an overview
      of how three complementary therapies integrate with modern healthcare, and will
      be useful for anyone who wants to learn about the therapies available, how they
      work, their evidence base and how they can be incorporated into NHS treatment.

PMID- 28745181
TI  - Praise for mental health staff, despite safety fears.
AB  - A fall in the number of mental health nurses has been linked to increased risk to
      patient safety, in an England-wide Care Quality Commission (CQC) report.

PMID- 28745182
TI  - Emergency put my skills to the test.
AB  - During a clinical placement on a general medical ward in my third year of
      training, I started managing a caseload of my own patients.

PMID- 28745183
TI  - 'Red carding' for relatives.
AB  - My colleagues and I recently looked after a patient on our acute trauma ward. The
      patient was well looked after, however her daughter made life very difficult for
      the nurses - to the point where the head of nursing visited daily to appease her.

PMID- 28745184
TI  - Immune T-cell discovery may inform lung cancer therapy.
AB  - A newly discovered immune cell could predict which patients with lung cancer
      would benefit most from immunotherapy.

PMID- 28745185
TI  - Readers' panel - Should GP surgeries introduce 'black alert' reporting systems?
AB  - Our experts consider a hot topic of the day.

PMID- 28745186
TI  - There's nothing like a bit of research to give flagging spirits a boost.
AB  - A recent study in Spain suggests that our month of birth can make us more
      susceptible to certain health conditions.

PMID- 28745187
TI  - Fresh focus on stroke care.
AB  - When 36-year-old company director Nathan Ridgard went to the emergency department
      with an excruciating headache and neck pain he was told he had a severe migraine
      and was admitted for tests.

PMID- 28745188
TI  - RCN plans 'biggest-ever rally' for pay cap protest.
AB  - The RCN is planning a rally in London to follow its summer of protest in a bid to
      force the government to scrap the public sector pay cap.

PMID- 28745190
TI  - Giving equal care to the 'difficult' patient.
AB  - One of our dogs, Ben, is a timid little thing. On a lead he can bark and growl,
      and to the untrained eye he must appear aggressive at times.

PMID- 28745191
TI  - Digital literacy.
AB  - Healthcare has been slower than many other sectors to embrace new technologies,
      with some nursing staff feeling anxious, fearful and sceptical about the digital
      revolution.

PMID- 28745192
TI  - Rescheduling of meals may ease the effects of jet lag.
AB  - Altering mealtimes could be a drug-free way to deal with the effects of jet lag
      and shift work.

PMID- 28745193
TI  - Support when it matters most.
AB  - A healthcare assistant's work to improve the experience of patients with a rare
      cancer was highly commended at the RCNi Nurse Awards 2017. Elaine Cooney, of
      Hampshire Hospitals NHS Foundation Trust, was recognised in the RCN Healthcare
      Assistant category for her work supporting patients with pseudomyxoma peritonei
      and their families.

PMID- 28745194
TI  - Mistakes happen, but we can change our response to them.
AB  - It's a heart-sinking feeling when you realise an error has been made, either by
      yourself or a colleague.

PMID- 28745195
TI  - NMC chief receives almost L20,000 pay rise after regulator conducts salary
      review.
AB  - Nursing and Midwifery Council chief executive Jackie Smith (pictured) received a
      pay rise of almost L20,000 in the past year, according to the regulator's annual
      report.

PMID- 28745196
TI  - Acid reflux treatment linked to higher risk of premature death.
AB  - Drugs used to treat acid reflux are linked to a heightened risk of premature
      death.

PMID- 28745204
TI  - Developing Family Medicine through education - the next steps.

PMID- 28745206
TI  - Sudden unexplained cardiac deaths in young adults: a call for multidisciplinary
      approach.
AB  - The investigation of death in young (<35 years), previously fit individuals,
      calls for a detailed autopsy with emphasis placed upon the examination of the
      heart. In most instances, the cause of cardiac death can be identified during
      autopsy. However, a large percentage of sudden deaths remain unexplained even
      after comprehensive medicolegal investigation, including autopsy, and are
      labelled as autopsy-negative sudden unexplained cardiac death (SUD). Still, when
      you look to the law, an autopsy, a much needed truth-finding-instrument, usually
      is not mandatory and is left up to the discretion of various medical or legal
      authorities, which when making a decision, balance various, often conflicting
      interests of the state and society on the one hand and of the deceased and his
      family on the other. Cardiac molecular autopsy calls for a close cooperation
      between medical examiner, pathologist, family physician, cardiologist,
      geneticist, and the relatives. Multidisciplinary approach and the identification
      of genetic cause of SUD enable proper genetic counselling for surviving relatives
      as well as for implementing specific preventive/therapeutic strategies, e.g.
      implantable cardioverter-defibrillator (ICD) implantation.

PMID- 28745207
TI  - HIV Drug Resistance Testing in a Resource Limited Setting with High Viral
      Diversity: The First Twenty Eight Months Experience.
AB  - BACKGROUND: First line antiretroviral therapy in a resource-limited setting
      consists of nucleotide and non-nucleotide reverse transcriptase inhibitors.
      Protease inhibitors are the hub of second line therapy. The decision to change
      antiretroviral therapy for a patient is frequently presumptive because of the
      lack of genotypic resistance tests in routine follow-up. We describe here the
      resistance profiles observed in patients with varying terms of antiretroviral
      therapy in Cameroon after implementation of HIV genotypic resistance testing in
      routine practice. METHODS: HIV genotypic resistance testing was carried out on
      consecutive samples received between August 2013 and November 2015. Protease
      (Prot) and reverse transcriptase (Rt) genes of the HIV genome were amplified,
      sequenced and analyzed for drug resistance mutations following the algorithm set
      up by the French National Agency for research on HIV/AIDS and viral hepatitis.
      RESULTS: Specimens from a total of 167 patients infected with non-B HIV subtypes
      were received during the study period. Overall 61.7% patients had viral loads of
      more than 3log copies/ml, suggesting treatment failure. Among the 72 patients on
      first line, 56 (77.8%) were resistant to Lamivudine, 57 (79.1%) to Efavirenz and
      58 (80.6%) to Nevirapine. Overall, more patients (75.0%) on first line
      antiretroviral therapy harbored multi-drug resistance compared to their
      counterparts on second line (25.8%). CONCLUSION: This study revealed that a group
      of patients with antiretroviral therapy failure harbored multi-drug resistance
      mutations related to the majority of drugs in the first line regimen. Therefore,
      HIV resistance testing could be a useful tool to improve HIV care in resource
      limited settings like Cameroon where treatment options are limited.

PMID- 28745208
TI  - Thiazole Containing Heterocycles with CNS Activity.
AB  - BACKGROUND: Thiazoles are promising scaffolds in the area of medicinal and
      pharmaceutical chemistry and have accounted to show different pharmacophoric
      properties. For the last years, thiazole derivatives have focused too much
      attention to develop different new CNS active agents. It has been broadly used to
      generate diverse therapeutic agents against various CNS targets. Histamine H3
      receptors are seriously involved in the pathophysiology of numerous disorders of
      the central nervous system. METHOD: The literature survey has been done using
      different database from peerreviewed journals. The quality of repossessed papers
      was evaluated using standard tools. The details of important papers were
      described to focus on the potency of thiazole containing heterocycles with CNS
      activity. RESULT: Eighty nine papers were included in the review indicating
      thiazole containing heterocycles with CNS activity. (1) to (30) papers included
      different thiazole derivatives impregnated withCNS activity. Different CNS agents
      have been shown in references (37) to (56). The remaining papers have been
      searched for anticonvulsant agents (57) to (78) and other miscellaneous
      activities from (79) to (89). CONCLUSION: A detailed investigation has been
      carried out on thiazoles and its derivatives to judge its efficacy to overcome
      several CNS disorders. This article covers the recent updates of thiazole and its
      derivative with CNS activity already present in literature and will definitely
      provide a better platform for the production and development of potent thiazole
      based CNS vigorous drugs in near future.

PMID- 28745209
TI  - Thiazole Containing Heterocycles with Antimalarial Activity.
AB  - BACKGROUND: Heterocyclic compounds are the main class of medicinally important
      compounds. Many heterocyclic compounds bearing a five-membered ring in their
      structure have a good spectrum of biological activities. Thiazole is an important
      class of five-membered heterocyclic compounds. Thiazole and its derivatives
      exhibited a broad range of biological activities due to the presence of various
      reaction posseses. Thiazole, heterocyclic nucleus is present in several potent
      pharmacologically active molecules such as Sulfathiazole (antimicrobial drug),
      Ritonavir (antiretroviral drug), Tiazofurin (antineoplastic drug) and Abafungin
      (antifungal drug) etc. The search for some novel biologically active thiazoles is
      to be continued in the field of medicinal chemistry for investigators. An aim of
      this review is to identify and try making a SAR (Structure Activity Relationship)
      of substituted thiazole nucleus as possible new antimalarials. METHOD: Author
      undertook a structured search of bibliographic databases for peerreviewed
      research literature using a focused review question and inclusion/exclusion
      criteria. The quality of retrieved papers was appraised using standard tools. The
      characteristics of screened papers were described, and a deductive qualitative
      content analysis methodology was applied to analyse the interventions and
      findings of included studies using a conceptual framework. RESULT: Fifteen papers
      were included in the review; the majority were described about many biological
      activity of thiazole nucleus. Seven papers were find that had impacted upon the
      thaizoles as antimalarials. Some papers focused on the design, synthesis and
      antimalarial activity evaluation of thiazole derivatives. This review identified
      and made a SAR (Structure Activity Relationship) of substituted thiazole nucleus
      as possible new antimalarials. CONCLUSION: This review describes ongoing research
      in the search for novel thiazoles as targets and new antimalarial drug molecules.

PMID- 28745210
TI  - Variability in Threshold for Medication Error Reporting Between Physicians,
      Nurses, Pharmacists, and Families.
AB  - BACKGROUND: Voluntary medication error reporting is an imperfect resource used to
      improve the quality of medication administration. It requires judgment by front
      line staff to determine how to report enough to identify opportunities to improve
      patients' safety but not jeopardize that safety by creating a culture of "report
      fatigue." OBJECTIVE: This study aims to provide information on interpretability
      of medication error and the variability between the subgroups of caregivers in
      the hospital setting. METHODS: Survey participants included nursing, physician
      (trainee and graduated), patient/families, pharmacist across a large academic
      health system, including an attached free-standing pediatric hospital.
      Demographics and survey questions were collected and analyzed using Fischer's
      exact testing with SAS v9.3. RESULTS: Statistically significant variability
      existed between the four groups for a majority of the questions. This included
      all cases designated as administration errors and many, but not all, cases of
      prescribing events. Commentary provided in the free-text portion of the survey
      was sub-analyzed and found to be associated with medication allergy reporting and
      lack of education surrounding report characteristics. CONCLUSION: There is
      significant variability in the threshold to report specific medication errors in
      the hospital setting. More work needs to be done to further improve the education
      surrounding error reporting in hospitals for all noted subgroups.

PMID- 28745211
TI  - The Lipid-lowering Effects and Associated Mechanisms of Dietary Phytosterol
      Supplementation.
AB  - Phytosterols (PS) are plant-based structural analogous of mammalian cholesterol
      that have been shown to lower blood cholesterol concentrations by ~10%, although
      inter-individual response to PS supplementation due to subject-specific metabolic
      and genetic factors is evident. Recent work further suggests that PS may act as
      effective triglyceride (TG)-lowering agents with maximal TG reductions observed
      in hypertriglyceridemic subjects. Although PS have been demonstrated to interfere
      with cholesterol and perhaps TG absorption within the intestine, they also have
      the capacity to modulate the expression of lipid regulatory genes through liver X
      receptor (LXR) activation. Identification of single-nucleotide polymorphisms
      (SNP) in key cholesterol and TG regulating genes, in particular adenosine
      triphosphate binding cassette G8 (ABCG8) and apolipoprotein E (apoE) have
      provided insight into the potential of utilizing genomic identifiers as an
      indicator of PS responsiveness. While PS supplementation is deemed safe,
      expanding research into the atherogenic potential of oxidized phytosterols
      (oxyphytosterols) has emerged with their identification in arterial lesions. This
      review will highlight the lipid-lowering utility and associated mechanisms of PS
      and discuss novel applications and future research priorities for PS pertaining
      to in utero PS exposure for long-term cardiovascular disease risk protection and
      combination therapies with lipidlowering drugs.

PMID- 28745212
TI  - MiRNA-based Therapeutic Strategy in Lung Cancer.
AB  - Lung cancer is one of the most common malignant tumors in the world. Although
      advanced therapies have been applied for the treatment of lung cancer, the
      prolongation of overall survival is limited due to treatment resistance.
      MicroRNAs (miRNAs) are a class of small non-coding, endogenous RNA molecules
      (about 19-23 nucleotides in length), which could regulate numerous human genes
      and play key roles in a variety of diseases. MiRNAs are dysregulated in lung
      cancer and participate in tumor initiation, development and drug resistance.
      Recent studies showed a new therapeutic strategy for cancer therapy based on
      miRNAs. In this review, we briefly summarize one classic pathway of miRNAs in
      lung cancer, and discuss a new miRNA-based therapeutic strategy to manage lung
      cancer.

PMID- 28745213
TI  - Emerging Roles of Meis1 in Cardiac Regeneration, Stem Cells and Cancer.
AB  - BACKGROUND: Meis1 is a member of three-amino-acid loop extension (TALE)
      homeodomain transcription factors. Studies in the last decade have shown that
      Meis1 has crucial roles in cardiac regeneration, stem cell function, and
      tumorigenesis. OBJECTIVE: We have recently demonstrated that knocking out of
      Meis1 in adult cardiomyocytes resulted in the induction of cardiomyocyte
      proliferation. This suggests that targeting of Meis1 might be utilized in the
      manipulation of cardiomyocyte cell cycle post cardiac injuries. In addition,
      hematopoietic stem cell (HSC) specific deletion of Meis1 leads to in vivo
      expansion of HSCs pool. Thus, targeting Meis1 may lead to not only cell cycle
      entry but also ex vivo and in vivo expansion of HSCs. On the other hand, Meis1
      transcriptionally regulates the expression of hypoxic tumor markers, namely Hif
      1alpha and Hif-2alpha. Hif-1alpha and Hif-2alpha are involved in the induction of
      cytoplasmic glycolysis and scavenging of reactive oxygen species (ROS),
      respectively. CONCLUSION: Studies highlight emerging roles of Meis1 towards
      development of new therapeutic approaches in the treatment of myocardial
      injuries, bone failure, and cancer.

PMID- 28745214
TI  - Nailfold Capillaroscopy of Fingers and Toes - Variations of Normal.
AB  - BACKGROUND: Nailfold capillaroscopy is the only method for morphological
      assessment of nutritive capillaries. The literature data about capillaroscopic
      findings in healthy individuals are scarce. OBJECTIVE: To evaluate and compare
      the capillaroscopic findings of fingers and toes in healthy subjects. MATERIALS
      AND METHODS: 22 healthy individuals were included in the study. Capillaroscopic
      examination was performed with videocapillaroscope Videocap 3.0 (DS Medica).
      Exclusion criteria were as follows: history of vasospasm, presence of
      accompanying diseases, taking any medications, arterial hypertension in first
      degree relatives, overweight or obesity (body mass index > 25kg/m2) and presence
      of chronic arterial or venous insufficiency. RESULTS: Poor visibility of nailfold
      capillaries was found significantly more frequently in the toes (22.7%, 5/22) as
      compared with fingers (0/22). Slight irregularities in capillary distribution and
      orientation to their parallel axis were significantly more common in the toes
      (31.8%, 7/22) as compared with fingers (9%, 2/22), (p<0.05). The mean diameter of
      the arterial (0.012+/-0.002mm) and the venous limb (0.017+/-0.002mm) of the toes
      did not differ significantly as compared to the respective parameters in the
      fingers (0.013+/-0.002mm for the arterial limb, p=0.46 and 0.018+/-0.002mm for
      the venous limb, p=0.25). The mean capillary density also did not differ
      significantly in the fingers and toes. The mean capillary length of the toes
      (0.165+/-0.096mm) was shorter as compared with hands (0.220+/-0.079mm), but the
      difference was not statistically significant (p=0.37). Presence of tortuous
      capillaries (>10%) was found significantly more often in the toes (12/22) as
      compared with fingers (6/22, chi2=6.769, p<0.05). Short capillary loops
      (length<100um) were observed significantly more often in the toes (11/22 - toes,
      1/22 - fingers, chi2=14.666, p<0.05). CONCLUSION: Capillaroscopic examination of
      the toes shows some differences as compared to those of the fingers such as
      greater number of cases with poor visibility and slight irregularities of
      distribution, greater number of shorter capillaries and increased tortuosity,
      which might be related to the thicker epidermis of the toes and increased
      capillary pressure due to gravity. The values of the major capillaroscopic
      parameters such as capillary diameters and capillary density in fingers and toes
      do not differ significantly.

PMID- 28745215
TI  - Nitroxyl Anion Mediates Relaxation in Mesenteric Arteries from Angiotensin II
      Hypertensive Mice.
AB  - AIMS: Nitroxyl anion (HNO) has recently become an emerging candidate in vascular
      regulation. NO- is a potent vasodilator of both conduit and small resistance
      vessels and mediates relaxation in a soluble guanylate cyclase-dependent manner.
      Interestingly, HNO activates voltage-dependent K+ (K+ V) channels, whereas Nitric
      Oxide (NO) activates calcium-activated K+ Ca channels. To date, there are few
      studies investigating the role of HNO in hypertension, and the possible
      mechanisms, which may be altered during this condition. We hypothesized that
      mesenteric arteries from angiotensin II-induced (AngII) hypertensive mice would
      exhibit an increased dependence upon NO- for relaxation, which may be mediated
      through K+ V channels. Methods and Key Results: C57/Bl6 mice, aged 12-14 weeks
      were implanted with mini-pumps containing angiotensin II (AngII, 3600ng/kg/min)
      for 14 days. For this study, we proposed to investigate the role of HNO in the
      resistance vasculature, and so first order mesenteric arteries were isolated and
      used in functional studies, or were frozen for Western blot analysis. We observed
      that mesenteric arteries from AngII mice (AngII) exhibited a decrease in HNO
      mediated relaxation, which was endotheliumindependent. With HNO scavenging by L
      cysteine [3mM], the maximal acetylcholine (ACh)-mediated relaxation response was
      decreased in sham, whereas mesenteric arteries from AngII exhibited a decrease in
      sensitivity. Incubation with the K+ V channel inhibitor, 4-aminopyridine [1mM],
      decreased AChmediated relaxation responses in sham, but almost completely
      abolished relaxation in AngII. CONCLUSION: We reveal that exogenous HNO-mediated
      relaxation, via Angeli's Salt, is impaired in mesenteric arteries from AngII
      treated mice, yet endogenous HNO-mediated relaxation may be more important during
      hypertension.

PMID- 28745216
TI  - Insights in Developmental Coordination Disorder.
AB  - BACKGROUND: Developmental Coordination Disorder (DCD) is a neurological
      impairment occurring in nearly 6% of general population, and sometimes mimics
      other developmental disorders like Attention Deficit Hyperactivity Disorder
      (ADHD) or, in the most severe cases, intellectual deficiency. OBJECTIVES: To
      review the general portrait of DCD, the physiology, the clinical assessments, and
      to provide an overview of functional studies on the subject. We finally report
      some proposed DCD managements which vary depending on the manifestation of the
      disorder and on the goals of the therapy. RESULTS: DCD can be stated as a sum of
      fine motor, perceptual visual and executive difficulties, emerging during
      childhood brain development and lasting throughout adulthood. Even if DCD can be
      isolated from other co-morbidities in certain individuals, it is still difficult
      to categorize it in delimited subclasses of characteristics, e.g. problems of
      vision or language. The findings in functional imaging also diverge in locating
      the cerebral deficit for a given motor task. CONCLUSION: Finding a single
      explanation seems difficult as many cerebral regions are associated with DCD and
      many clinical aspects are involved, but, further studies could explore genetic
      (or epigenetic) explanation for the prevalence of DCD in population.

PMID- 28745217
TI  - Evaluation of Salivary Melatonin Levels in HIV-positive Patients: A Historical
      Cohort Study.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) affects lymphocytes, resulting in
      acquired immunodeficiency syndrome. Oxidative stress may play an important role
      in HIV pathogenesis. Melatonin has antioxidant, antiinflammatory and
      immunomodulatory effects. OBJECTIVE: The aim of this study was to evaluate
      salivary melatonin levels in HIV-positive patients and a healthy control group.
      METHODS: Forty-nine HIV-positive and 49 healthy subjects were included in this
      study. Patients' drug consumption and clinical examination results were
      registered in questionnaires. Unstimulated whole saliva was collected in the
      morning. The melatonin levels were measured by melatonin ELISA kits. Statistical
      analyses were performed with STATA 12, using t-test and chi-squared test.
      RESULTS: Salivary melatonin levels were significantly lower in the case group in
      comparison with the healthy control group (P=0.001). Age was significantly higher
      in the case group. Chi-squared test showed no statistically significant
      difference between the case and control groups in smoking (P=0.591) and addiction
      (P=0.204) but gender differences were observed (P=0.001). CONCLUSION: Salivary
      melatonin level as an antioxidant was lower in HIV-positive patients. Further
      studies are necessary to understand the exact role of melatonin in HIV-positive
      patients and its therapeutic effects.

PMID- 28745218
TI  - Ventricular Extrasystoles after First Dose of Sofosbuvir in a Patient Treated
      with Propranolol but not with Amiodarone: A Case Report.
AB  - BACKGROUND: Sofosbuvir is a direct-acting antiviral drug used to treat chronic
      hepatitis C infection. In 2015, Gilead Sciences, the manufacturer of sofosbuvir,
      warned that bradycardia could occur when sofosbuvir is administered in
      combination with amiodarone. Interestingly, among the reported cases of patients
      with sofosbuvir and amiodarone related bradycardia, some of them were also
      treated with propranolol. OBJECTIVE: We herein report a case of ventricular
      extrasystoles within three hours after the coadministration of sofosbuvir
      containing regimen with propranolol. This patient had never been treated with
      amiodarone. After the sofosbuvir-containing regimen was stopped, ventricular
      extrasystoles disappeared within 24 hours. This observation suggests that the
      association of sofosbuvir with propranolol may have a role in the emergence of
      cardiac arrhythmia. CONCLUSION: Patients treated with amiodarone and/or
      propranolol should be continuously monitored within the early hours following the
      initiation of sofosbuvir.

PMID- 28745219
TI  - The Influence of Vaccine on Febrile Seizure.
AB  - BACKGROUND: The protective value of vaccines to the public has made vaccines
      among the major public health prophylactic measures through the entire history.
      However, there has been some controversy about their safety; particularly
      concerns have been rising about febrile seizures (FS). Vaccination was found to
      be the second most common cause of FS. METHODS: We research and collect relative
      online content for reviewing the effects of vaccine in FS. RESULTS: there is no
      causal relationship between FS and vaccination. This relationship is complex by
      other factors, such as age, genetic inheritance, type of vaccine, combination of
      different types of vaccines and the timing of vaccination. CONCLUSION: In order
      to reduce FS after vaccination, it is important to understand the mechanism of
      epilepsy and relationship between specific vaccines and FS. Parents should be
      informed that some vaccines could be associated with an increased risk of FS,
      particularly, in children with personal and family history of FS. Children with
      genetic epilepsy syndrome are prone to seizures and certain vaccinations should
      be avoided in these children. It is highly recommended to choose vaccines with
      lower risk of developing FS and to administer these vaccines during the low risk
      window of immunizations schedule.

PMID- 28745220
TI  - Tuftsin - Properties and Analogs.
AB  - BACKGROUND: Immunomodulation is one of the significant therapeutic strategies. It
      includes both stimulation and suppression of the immune system by a variety of
      substances called immunomodulators, designed to regulate the immune response of
      the organism against infections of varying etiology. An example of such a
      substance is tuftsin (TKPA) 3 (Fig. (1)). In this paper were included tuftsin
      derivatives, which were described over the years, their together with biological
      activity and clinical potential. METHODS: We reviewed a bibliographic database to
      gather all the important information about the tuftsin peptide. We have
      delineated the significant information on the activity of the tetrapeptide itself
      and its derivatives. Analogs were divided because of their anti-tumor, anti
      inflammatory, antimicrobial and anti-viral activity. RESULTS: This paper
      describes eighty-six documents. Thirty-two of them concern on activity of tuftsin
      in the human organism. The remaining fifty-four describe peptide analogues and
      their properties, including eleven papers about the tuftsin-based peptides
      contained in the vaccines, nine papers representing anticancer activity of the
      tuftsin derivatives, twenty-six about antiinflammatory compounds, and five papers
      describing the antitumor activity of the tuftsin analogs. CONCLUSION: The
      findings of this review confirm the importance of the tuftsin and their
      derivatives. Most of these substances showed anti-tumor, anti-inflammatory or
      antibacterial activities. A large amount of the compounds may find use in
      vaccines. Tuftsin can also be used to prepare fusion proteins in the treatment of
      cancer and as carriers of many biologically active substances.

PMID- 28745221
TI  - Rheumatic Heart Disease: Pathogenesis and Vaccine.
AB  - Rheumatic fever (RF) and rheumatic heart disease (RHD) follow untreated S.
      pyogenes throat infections in children who present susceptible genes that favor
      the development of autoimmune reactions. In this review, we focus on the genes
      that confer susceptibility and on the autoimmune reactions that occur due to
      molecular mimicry between human-tissue proteins and streptococcal M protein.
      Polyarthritis is the initial manifestation, which can evolve to carditis and
      severe valve damage; these culminate in rheumatic heart disease (RHD) or
      Sydenham's chorea, which affects the central nervous system. A perspective on
      vaccine development to prevent the disease is also discussed.

PMID- 28745222
TI  - Impact of Hydroxyl Radical Modified-Human Serum Albumin Autoantigens in Systemic
      Lupus Erythematosus.
AB  - Free radicals are important mediators for cell toxicity and pathogenesis of
      diseases. Reactive oxygen species (ROS) have been generated broadly in
      inflammatory diseases including autoimmune diseases. ROS have been not only
      associated with the initiation and progression of the autoimmune response but
      also in amplification and exploring to novel epitopes, through the unveiling of
      antigenic determinants. This review explores the involvement of ROS in the
      pathophysiology of non-organ specific autoimmune diseases like systemic lupus
      erythematosus (SLE). The modification of human serum albumin through hydroxyl
      radical is thought to be responsible for the induction of autoantibodies against
      modified human serum albumin. In the light of overwhelming evidence suggesting
      the association with oxidative damage in autoimmunity, the administration of
      antioxidants could be a viable alternative for the neutralization of free
      radicals that are involved in eliciting autoimmune disease. In this review, we
      have discussed their pro-oxidant as well anti-oxidant properties which are
      capable of differentially modulating the autoimmune response.

PMID- 28745223
TI  - Structure, Function of Serine and Metallo-beta-lactamases and their Inhibitors.
AB  - Antibiotic resistance in gram-negative bacteria has emerged as a major health
      threat that occurs because these bacteria actively produce beta-lactamases
      responsible for the inactivation of beta-lactam antibiotics. The first beta
      lactamase was reported in E. coli back in 1940, before the release of the first
      antibiotic penicillin in clinical settings. Later on, large numbers of beta
      lactamases have been discovered in Gram-positive, Gram-negative bacteria as well
      as mycobacteria. Currently, numerous three-dimensional structures of serine and
      metallo-beta-lactamases have been solved. The serine beta-lactamases essentially
      consist of two structural domains (an all alpha and an alpha/beta domain) and the
      active site is located at the groove between the two domains. The catalysis of
      serine beta-lactamase proceeds via acylation and deacylation reactions. The three
      dimensional structure of metallo-beta-lactamases displayed a common four layer
      "alphabeta/betaalpha" motif, with a central "betabeta"- sandwich by Zn2+ ion(s),
      and two alpha-helices are located on the either side. The active site of metallo
      beta-lactamases contain either 1 or 2 Zn2+ ions, which is coordinated to metal
      ligating amino acids and polarized water molecule(s) necessary for the hydrolysis
      of beta-lactam antibiotics. Keeping the above views in mind, in this review we
      have shed light on the current knowledge of the structures and mechanisms of
      catalysis of serine and metallo-beta-lactamases. Moreover, mutational studies on
      beta-lactamases highlight the importance of the active site residues and residues
      in the vicinity to the active site pocket in the catalysis. To combat bacterial
      infections more effeciently novel inhibitors of beta-lactamase in combination
      with antibiotics have been used which also form the theme of the review.

PMID- 28745224
TI  - Editorial: Research and Selection of Multitarget Compounds in Medicinal
      Chemistry.

PMID- 28745225
TI  - Preface.

PMID- 28745226
TI  - Spatiotemporal Gait Characteristics Associated with Cognitive Impairment: A
      Multicenter Cross-Sectional Study, the Intercontinental "Gait, cOgnitiOn &
      Decline" Initiative.
AB  - BACKGROUND: The study aims to determine the spatiotemporal gait parameters and/or
      their combination(s) that best differentiate between cognitively healthy
      individuals (CHI), patients with mild cognitive impairment (MCI) and those with
      mild and moderate dementia, regardless of the etiology of cognitive impairment.
      METHODS: A total of 2099 participants (1015 CHI, 478 patients with MCI, 331
      patients with mild dementia and 275 with moderate dementia) were selected from
      the intercontinental "Gait, cOgnitiOn & Decline" (GOOD) initiative, which merged
      different databases from seven cross-sectional studies. Mean values and
      coefficients of variation (CoV) of spatiotemporal gait parameters were recorded
      during usual walking with the GAITRite(r) system. RESULTS: The severity of
      cognitive impairment was associated with worse performance on all gait
      parameters. Stride velocity had the strongest association with cognitive
      impairment, regardless of cognitive status. High mean value and CoV of stride
      length characterized moderate dementia, whereas increased CoV of stride time was
      specific to MCI status. CONCLUSION: The findings support the existence of
      specific cognitive impairment-related gait disturbances with differences related
      to stages of cognitive impairment, which may be used to screen individuals with
      cognitive impairment.

PMID- 28745227
TI  - Frontotemporal Lobar Degeneration (FTLD): Review and Update for Clinical
      Neurologists.
AB  - BACKGROUND: Frontotemporal Dementia (FTD) is a heterogeneous group of disorders
      and the second most frequent cause of early onset dementia making it the highest
      number of inherited cases. REVIEW SUMMARY: FTD is characterized by considerable
      variability in clinical, genetic and histopathologic features. Patients may
      present symptoms ranging from behavioural disturbances to different language
      disorders, with or without motor neuron disorders or associated parkinsonism.
      Atrophy in frontal and temporal lobes is the most relevant radiological finding.
      In the last 10 years, the knowledge of this clinical entity has undergone
      remarkable changes both genetically and histopathologically, which have served to
      establish more consistent clinical criteria. Until now, 10 genes causative of
      FTLD have been described and up to four different proteins causative of atrophy
      have been detected in aggregates. CONCLUSION: This review is mostly addressed to
      clinicians and aims to provide basic knowledge of these neurodegenerative
      disorders and clarify the complex FTD scenario.

PMID- 28745228
TI  - Advances in the Delivery of Cancer Therapeutics: A Comprehensive Review.
AB  - BACKGROUND: The effects of various chemotherapeutic agents have been assessed for
      their capacity to inhibit the cell replication in variety of cancer cases. At
      present there are more than hundred chemotherapeutic agents capturing worth 42
      billion dollar of drug market. The major obstacle in the successful treatment of
      cancer is the obnoxious side effects of chemotherapeutics and multi drug
      resistance, which deteriorates the quality of life of cancer patient. OBJECTIVE:
      This article attempts to summarize different novel chemotherapeutic delivery
      systems which aim to circumvent these unwanted effects. Areas Covered: Outcomes
      of different tumor directed carrier systems have been discussed with special
      emphasis on nanocarriers systems, drug polymer conjugation, directly implantable
      matrices and others. In addition, combination therapy and immunotherapy are also
      discussed as a revolutionary alternative. CONCLUSION: Even though significant
      contributions have been made in the development of carrier systems for the
      chemotherapeutic agents, merits and demerits of all the avenues should be
      critically examined. Potential of all novel strategies should be exploited by
      critically evaluating their strength, weakness, opportunities and threats.
      Further, clinical trials based on revised and critically scrutinized frameworks
      and protocols are needed so that the efficiency and safe action of these new
      systems can be guaranteed in cancer patients.

PMID- 28745229
TI  - Delivering Resveratrol on the Buccal Mucosa Using Mucoadhesive Tablets: A
      Potential Treatment Strategy for Inflammatory Oral Lesions.
AB  - BACKGROUND: Resveratrol is a polyphenol that has gained momentum in therapeutics
      in the last few years. OBJECTIVE: In this study, we hypothesised that resveratrol
      could act prophylactically and/or treat inflammatory lesions of the oral cavity
      after being delivered by two different formulations of buccal mucoadhesive
      tablets (F1 and F2, which differed in terms of viscosity agents used). METHODS:
      This hypothesis was assessed through permeation studies, to verify diffusion of
      the drug through the buccal mucosa using a porcine model to predict human in vivo
      behaviour. RESULTS: F2 (tablet with less viscosity agent) presented better
      permeation than F1, but the amount of drug that crossed the mucosa was still low
      compared to the amount retained within it (35.90 ug found in the receptor medium
      and 15.63 mg quantified within the mucosa). CONCLUSION: This accounted for a
      local effect rather than a systemic one, which is desirable for local processes,
      such as oral mucositis, lichen planus, erythema multiforme, nicotinic stomatitis,
      recurrent aphthous stomatitis, among others. In this sense, resveratrol-loaded
      mucoadhesive tablets appear to be a prominent alternative to prevent and/or cure
      inflammatory lesions of the oral cavity.

PMID- 28745230
TI  - Bupivacaine (S75:R25) Loaded in Nanostructured Lipid Carriers: Factorial Design,
      HPLC Quantification Method and Physicochemical Stability Study.
AB  - BACKGROUND: Bupivacaine is the most used local anesthetic in surgical procedures,
      producing prolonged anesthesia. The major limiting factor for the clinical use of
      bupivacaine comes from its systemic toxicity. Nanostructured lipid carriers (NLC)
      are vehicles for sustained drug delivery that are able to minimize the toxicity
      and to increase the action time of lipophilic drugs. METHODS: This work reports a
      22 factorial design, which elucidates the role of the lipids mixture in the NLC,
      towards an optimized formulation. It also provides a new method for bupivacaine
      S75:R25 (BVCS75) quantification in NLC. Moreover, physicochemical stability
      studies on the prepared NLC formulations were carried out by monitoring particle
      size, polydispersity, Zeta potential and BVCS75 encapsulation efficiency for 90
      days, at 25 degrees C. RESULTS: The factorial design showed that the liquid lipid
      Capryol 90(r) has a negative effect over particle size and PDI values while cetyl
      palmitate presented a positive effect in size. The analytical method was
      accurate, reproducible, specific and linear over the concentration range of 0.16
      54.00 ug.mL-1 BVCS75 with limits of quantification and detection of 0.10 and 0.03
      ug.mL-1, respectively. The validated method was used to quantify the BVCS75
      encapsulation (55.5 +/-2.8 %). Encapsulation did not affect the nanoparticles
      morphology (confirmed by Transmission Electron Microscopy), but increased their
      Zeta potential (from -15.7 to -37.0 mV). The NLC physical stability was
      maintained (particles: size < 170 nm, polydispersity <0.16, and number = 8.85 +/
      0.11 x 1013 particles.mL-1) during storage. CONCLUSION: These results support
      further investigations on the use of BVCS75-in-NLC formulation for surgical
      anesthesia, aiming the development of a potent and less toxic nanostructured
      lipid carrier formulation for BVCS75.

PMID- 28745231
TI  - Synthesis and Antimalarial Activity of New Enantiopure Aminoalcoholpyrrolo[ 1,2
      a]quinoxalines.
AB  - BACKGROUND: We prepared a novel series of enantiopure mefloquine analogues with
      pyrrolo[ 1,2-a]quinoxaline core in order to fight Plasmodium falciparum resistant
      strain. OBJECTIVES: To observe the influence of pyrrolo[1,2-a]quinoxaline core
      versus quinoline core on the antimalarial activity. METHOD: Four enantiopure
      aminoalcoholpyrrolo[1,2-a]quinoxalines 2 were synthetized via Sharpless
      asymmetric dihydroxylation reaction in eight steps. Their antimalarial activity
      was evaluated on two Plasmodium falciparum strains 3D7 and W2 with a SYBR Green I
      fluorescence-based method and their cytotoxicity was measured on four cell lines
      HepG2, THP-1, CHO and HFF. RESULTS: IC50 values of the four compounds 2 were
      close to the micromolar against the two P. falciparum strains. They were more
      active against P. falciparum strain W2 vs. P. falciparum strain 3D7. (R)-
      enantiomers were always more active than their (S)-counterpart whatever the
      strain. Selectivity indexes of compounds 2 were lower than 100. CONCLUSION: A
      novel series of enantiopure aminoalcohols with pyrrolo[1,2-a]quinoxaline core
      were synthesized in eight steps. They displayed IC50 values close to the
      micromolar against two P. falciparum strains 3D7 and W2. Although, In this
      series, 2,8-bistrifluoromethylquinoline was a best core than pyrrolo[1,2
      a]quinoxaline for an optimal antimalarial activity, the pyrroloquinoxaline 2b
      showed an interesting antimalarial activity.

PMID- 28745232
TI  - In vitro alpha-Glucosidase Inhibition by Non-sugar based Triazoles of
      Dibenzoazepine, their Structure-Activity Relationship, and Molecular Docking.
AB  - BACKGROUND: alpha-Glucosidase inhibitors (AGIs) have been reported for their
      clinical potential against postprandial hyperglycemia, which is responsible for
      the risks associated with diabetes mellitus 2 and cardiovascular diseases (CVDs).
      Besides, a number of compounds have been reported as potent AGIs, several side
      effects are associated with them. METHODS: The aim of present work is to explore
      new and potent molecules as AGIs. Therefore, a library of dibenzoazepine linked
      triazoles (1-15) was studied for their in vitro alpha-glucosidase inhibitory
      activity. The binding modes of potent compounds in the active site of alpha
      glucosidase enzyme were also explored through molecular docking studies. RESULTS
      AND CONCLUSION: Among the reported triazoles, compounds 3-9, 11, and 13 (IC50 =
      6.0 +/- 0.03 to 19.8 +/- 0.28 uM) were found to be several fold more active than
      the standard drug acarbose (IC50 = 840 +/- 1.73 uM). Compound 5 (IC50 = 6.0 +/-
      0.03 uM) was the most potent AGIs in the series, about 77- fold more active than
      acarbose. Therefore, dibenzoazepine linked-triazoles described here can serve as
      leads for further studies as new non-sugar AGIs.

PMID- 28745233
TI  - Foreword.

PMID- 28745234
TI  - Editorial: Bioactive Proteins and Peptides.

PMID- 28745235
TI  - Effects of Ascorbic Acid on Tax, NF-kappaB and MMP-9 in Human T-cell Lymphotropic
      Virus Type 1 Positive Malignant T-Lymphocytes.
AB  - BACKGROUND: HTLV1 is a retrovirus that infects CD4-positive cells and leads to
      Adult T-cell leukemia by constitutive activation of nuclear factor kappa B.
      Ascorbic acid (AA) is an essential nutrient that possess anti-proliferative and
      pro-apoptotic activity against a number of malignant cell lines. This study
      delineates the effect of AA on Tax protein expression as well as NF-kappaB and
      MMP9 activity in two HTLV1-positive leukemia cells (HuT-102 and C91-PL). METHODS:
      The cytotoxic and antiproliferative effect of AA were studied by LDH release and
      MTT tests, respectively. The proteins expression level was assessed by western
      blotting. RT-PCR was used to study mRNAs level. Finally, ELISA/EMSA and
      Zymography were used to evaluate NF-kappaB and MMP-9 activities, respectively.
      RESULTS: Cell lines were treated with non-cytotoxic concentrations of AA for 48h
      and 96h, which resulted in a significant inhibition of proliferation at a
      concentration of 50ug/ml at 96h in both cell lines. The same concentration
      inhibited Tax protein expression as well as the NF-kappaB nuclearization and DNA
      binding activity. The inhibitory effect of AA on MMP9 protein expression and
      activity started at 100ug/ml and 50ug/ml in HuT-102 and C91-PL cells
      respectively, with no effect at the transcriptional levels of MMP-9 in either one
      of the two cell lines. CONCLUSION: These results indicated that while AA exerted
      its anti-proliferative effect on the NF- kappaB activation pathway by suppressing
      Tax expression, its effects on MMP9 seemed to be independent of this mechanism
      and follow a different approach.

PMID- 28745236
TI  - Synthesis of Pyridine and Spiropyridine Derivatives Derived from 2-aminoprop- 1
      ene-1,1,3-tricarbonitrile Together with their c-Met Kinase and Antiproliferative
      Evaluations.
AB  - BACKGROUND: Among a wide range of pyridines, 3-cyanopyridines acquired a special
      attention due to their wide range of pharmacological activities especially the
      therapeutic activities. Many pharmacological drugs containing the pyridine
      nucleus were known in the market. OBJECTIVE: The aim of this work was to
      synthesize target molecules not only possess anti-tumor activities but also
      kinase inhibitors. To achieve this goal, our strategy was to synthesize a series
      of 3-cyanopyridine derivatives using 2-aminoprop-1-ene-1,1,3-tricarbonitrile (1)
      as the key starting material for many heterocyclization reactions. METHOD:
      Muticoponent reactions were adopted using compound 1 to get different pyridine
      derivatives that were capable for different heterocyclization reactions. RESULTS:
      Antiproliferative evaluations and c-Met kinase, Pim-1 kinse inhibitions were
      perform where some compounds gave high activities. CONCLUSION: Compounds that
      showed high antiprolifeative activity were tested gor c-Met-independent and the
      results showed that compounds 5c, 5e, 5f, 7c, 7f and 16d were more active than
      foretinib. The Pim-1 kinase inhibition activity of some selected compounds showed
      that compounds 5e and 16c were high potent to inhibit Pim-1 activity.

PMID- 28745237
TI  - Anethole Inhibits the Proliferation of Human Prostate Cancer Cells via Induction
      of Cell Cycle Arrest and Apoptosis.
AB  - BACKGROUND: Prostate cancer-associated mortality is increasing at an alarming
      rate, which highlights the inevitability for unearthing novel agent for the
      management of this disease. Anethole, a major constituent of Foeniculum vulgare
      (fennel) essential oil, is widely used in folk medicine; it possesses anti
      oxidant, antiinflammatory, anti-proliferative and tumoricidal potentialities.
      OBJECTIVE: The current research was conducted to assess the impact of anethole on
      prostate cancer cell line, PC- 3, and to delineate the molecular mechanism of
      action. METHODS: To achieve this aim, the growth-inhibitory effect of anethole
      was evaluated by MTT assay. Apoptotic death and cell cycle analyses were assessed
      by flow cytometry and alterations in gene expression were investigated by qPCR
      and Western blot analyses. RESULTS: The observations indicated that anethole
      inhibited proliferation, clonal growth and migration of PC-3 cells. It also
      suppressed growth of PC-3 derived cancer stem cells (tumorspheres). Pro-apoptotic
      potential of anethole was accompanied by generation of ROS, permeabilization of
      the mitochondrial and lysosomal membranes, activation of caspase-3 and -9, DNA
      damage, PARP cleavage and induction of Bax/Bcl-2 protein ratio. Further, anethole
      induced G2/M phase arrest, downregulation of cyclins D1, CDK-4 and c-Myc proteins
      and upregulation of p21 and p27. Anethole suppressed nuclear localization of NF
      kappaB protein and downregulated transcription of NF-kappaB-dependent genes.
      CONCLUSION: Overall, the above findings highlight the effectiveness of anethole
      as a potential candidate for prostate cancer therapy.

PMID- 28745238
TI  - Effect of Number of Bifunctional Chelating Agents on the Pharmacokinetics and
      Immunoreactivity of 177Lu-labeled Rituximab: A Systemic Study.
AB  - OBJECTIVE: Monoclonal antibodies (mAbs) have been radiolabeled with a variety of
      radioisotopes utilizing various kinds of bi-functional chelating agents (BFCAs)
      with an aim to develop suitable agents for radioimmunotherapy. The number of BFCA
      moieties present per antibody molecule plays a significant role in determining
      the pharmacokinetics and immunoreactivity exhibited by the radiolabeled
      antibodies. The objective of the present study is to evaluate the effect of the
      number of BFCA moieties present per antibody molecule on the pharmacokinetics and
      immunoreactivity of the 177Lu-labeled Rituximab. METHODS: Three different mAb
      BFCA conjugates were prepared using different molar ratios of Rituximab (mAb) to
      p-NCS-benzyl-DOTA (BFCA) viz. 1:5, 1:10 and 1:50 employing different reaction
      conditions. Studies were carried out to determine the average number of BFCAs
      attached per mAb molecule. All the three mAb-BFCA conjugates were labeled with
      177Lu(III) and were subsequently evaluated in normal Swiss mice to ascertain
      their respective pharmacokinetic behavior. In-vitro studies were also performed
      in Raji cell lines (human burkitt's lymphoma) for determining the effect of
      increasing number of BFCAs attached per mAb molecule on the immunoreactivity of
      the resultant 177Lu-labeled mAb-BFCA complexes. RESULTS: 177Lu-labeled mAb-BFCA
      complex prepared corresponding to 1:50 mAb to BFCA ratio exhibited the least non
      specific uptake and rapid clearance from majority of the organs, but also
      exhibited least immunoreactive fraction (IRF = 19.37%). On the other hand, 177Lu
      labeled mAb-BFCA complex prepared corresponding to 1:5 mAb to BFCA ratio
      exhibited the highest non-specific uptake and slower clearance pattern, but
      highest IRF (71.17%). 177Lu-labeled mAb-BFCA complex prepared corresponding to
      1:10 mAb:BFCA ratio exhibited intermediate pharmacokinetic behaviour with
      moderate IRF (53.05%). CONCLUSIONS: The present study indicates that antibody to
      BFCA ratio plays a crucial role in determining the immunoreactivity and
      pharmacokinetic behavior of the radiolabeled antibodies and must be prudently
      chosen for their successful therapeutic application.

PMID- 28745240
TI  - Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-kappaB) - a
      Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis
      of Alzheimer's Disease.
AB  - BACKGROUND: NF-kappaB is a ubiquitous transcription factor that was discovered
      three decades ago. Since its discovery, this protein complex has been implicated
      in numerous physiological and pathophysiological processes such as synaptic
      plasticity, learning and memory, inflammation, insulin resistance, and oxidative
      stress among other factors that are intricately involved and dysregulated in
      Alzheimer's disease (AD). METHODS: We embarked on a methodical and an objective
      review of contemporary literature to integrate the indispensable physiological
      functions of NF-kappaB in neuronal phsyiology with the undesirable
      pathophysiological attributes of NF-kappaB in the etiopathogenesis of Alzheimer's
      disease. In our approach, we first introduced Alzheimer's disease and
      subsequently highlighted the multifaceted roles of NF-kappaB in the biological
      processes altered in the progression of Alzheimer's disease including synaptic
      transmission, synaptic plasticity, learning, and memory, neuronal survival and
      apoptosis, adult neurogenesis, regulation of neural processes and structural
      plasticity, inflammation, and Amyloid-beta production and toxicity. RESULTS: Our
      comprehensive review highlights and dissects the physiological role of NF-kappaB
      from its pathological role in the brain and delineates both, its beneficial as
      well as deleterious, role in the etiopathogenesis of Alzheimer's disease.
      CONCLUSION: In light of our understanding of the duality of the role of NF-kappaB
      in the pathogenesis of Alzheimer's disease, further studies are warranted to
      dissect and understand the basis of the dichotomous effects of NF-kappaB, so that
      certain selective benevolent and benign attributes of NF-kappaB can be spared
      while targeting its deleterious attributes and facets that are integral in the
      pathogenesis of Alzheimer's disease.

PMID- 28745241
TI  - The Role of Innate Immune System Receptors in Epilepsy Research.
AB  - BACKGROUND & OBJECTIVE: Epilepsy is one of the most complex neurological
      disorders and its study requires a broad knowledge of neurology and neuroscience.
      It comprises a diverse group of neurological disorders that share the central
      feature of spontaneous recurrent seizures, and are often accompanied by cognitive
      deficits and mood disorder. This condition is one of the most common neurological
      disorders. Until recently, alterations of neuronal activities had been the focus
      of epilepsy research. This neurocentric emphasis did not address issues that
      arise in more complex models of epileptogenesis. An important factor in epilepsy
      that is not regulated directly by neurons is inflammation and the immune response
      of the brain. Recent evidence obtained in rodent epilepsy models supports the
      role of immune responses in the initiation and maintenance of epilepsy.
      Recognition of exogenous pathogens by the innate immune system is mediated by
      some pattern recognition receptors such as Toll-like receptors leading to cell
      activation and cytokine production. Currently, these receptors have been the
      focus of epilepsy studies looking to determine whether the innate immune
      activation is neuroprotective or neurotoxic for the brain. CONCLUSION: Here, we
      present the evidence in the literature of the involvement of key innate immune
      receptors in the development of epilepsy. We address some of the contradictory
      findings in these studies and also mention possible avenues for research into
      epilepsy treatments that target these receptors.

PMID- 28745242
TI  - Leber's Hereditary Optic Neuropathy: Novel Views and Persisting Challenges.
AB  - BACKGROUND & OBJECTIVE: Leber's hereditary optic neuropathy is an inherited form
      of optic neuropathy, genetically and pathophysiologically based on mitochondrial
      insufficiency causing bilateral loss of central vision mostly amongst young
      adults. Despite being one of the most common mitochondrial diseases, the
      explanation for its pathophysiological background and effective clinical
      solutions remain elusive. Widening the scope in the search for pathological
      findings beyond the optic system has yielded several non-ophthalmologic findings,
      which might imply that Leber's hereditary optic neuropathy is in fact a multi
      systemic disease. CONCLUSION: The aim of this review is to provide an overview of
      literature regarding the epidemiology, etiology, pathogenesis, clinical features,
      diagnostics and possible treatment options and drug targets, as well as
      presenting challenges related to the disease and proposing a diagnostic algorithm
      based on current clinical experience.

PMID- 28745243
TI  - [An image says more than a thousand words; standardising video registration in
      the operating theatre].
AB  - Today, video imaging is a major part of laparoscopic surgery. Despite continuous
      efforts to improve or innovate laparoscopic techniques, the registration of
      laparoscopic imaging for quality of care purposes remains an afterthought. By
      recording the essential steps of a surgical procedure, it is possible to inquire
      in more detail about what actually occurred in the operating theatre. However, it
      is necessary to take the legal framework into account. Questions concerning
      patient consent, permission from healthcare providers, whether video
      documentation should enter the patient record, and the length of the period it is
      retained must be answered. Also, the prevention of the misuse of information is
      important and therefore the purpose of documentation needs to be put on record
      beforehand. Video documentation is a promising method of registering surgical
      quality. However, the first priority is to demonstrate the actual quality
      improvement of video documentation and the formulation of precise guidelines.

PMID- 28745244
TI  - [Large part of The Hague children taking too little vitamin D].
AB  - OBJECTITVE: To investigate the extent to which 0-15-year-old children in The
      Hague are complying with Dutch Health Council vitamin D supplementation advice,
      and whether there are differences between ethnic groups. DESIGN: Cross-sectional
      study. METHOD: From November 2014 up to and including October 2015, The Hague
      organisations for youth health care (YHC) have recorded intake of vitamin D
      supplementation during standard consultations. YHC 0-4 recorded whether vitamin D
      supplementation intake was sufficient. YHC 4-18 recorded whether vitamin D
      supplementation was recommended for the child (aged 4 and older, in case of
      coloured skin or insufficient time spent outdoors) and whether this child took
      sufficient vitamin D supplementation. Information on ethnic origin was taken from
      the digital YHC records. RESULTS: A large majority of those aged 0-3 received
      sufficient vitamin D supplementation. Intake was unknown for most 4-year-olds.
      Vitamin D supplementation was recommended for half of the children aged 5 or
      older, but a substantial number of them received no (50%) or insufficient (18%)
      supplementation. Among children for whom extra vitamin D was recommended, there
      was little difference in vitamin D use between ethnic groups. CONCLUSION: The
      Dutch Health Council recommendation on vitamin D supplementation is intended to
      prevent vitamin D deficiencies, but there is insufficient compliance by children
      in The Hague, especially those aged five and older.

PMID- 28745245
TI  - [Bariatric surgery: who, when and where?; an overview for the referring
      physician].
AB  - - Bariatric surgery is performed in patients with a body mass index (BMI) >
      40kg/m2, or BMI > 35 kg/m2 with obesity-related comorbidities. The Roux-en-Y
      gastric bypass and sleeve gastrectomy are the most frequently used procedures.-
      On average, patients have lost 25-27% of their original weight 10 years after
      surgery.- Obesity-related comorbidities improve dramatically in many patients
      following surgery. The effect is most noticeable in patients with diabetes
      mellitus type 2 and obstructive sleep apnoea syndrome. - The prevalence of 30-day
      complications is < 5%. Mortality is < 0.2% in centres with a lot of experience. -
      Commonly occurring long-term complications of bariatric surgery include
      deficiencies, particularly of iron and vitamin B12, along with gallstone disease
      and sagging skin. - Specific complications can arise following Roux-en-Y gastric
      bypass, such as internal herniation and hypoglycaemia, and these are often not
      recognised.

PMID- 28745246
TI  - [A skin lesion with ghost cells].
AB  - An 83-year-old woman presented with painful erythematous nodules on her feet and
      legs. Recently, she had been admitted several times because of pancreatitis of
      unknown cause. A biopsy showed fat cell necrosis with ghost cells and the
      diagnosis of pancreatic panniculitis was made.

PMID- 28745247
TI  - [Georg Friedrich Nicolai: war physician against war].
AB  - Georg Friedrich Nicolai was a German professor and heart specialist who was one
      of the few who protested against the war at the beginning of World War I. As a
      result, he lost his job and was convicted. After the war, right-wing nationalist
      students and lack of support from his university superiors made it impossible for
      him to teach. He left Germany in 1922, never to return. In his book, Die Biologie
      des Krieges (The Biology of War), which was published in neutral Switzerland in
      1917, he contradicted the social Darwinist idea - supported by many physicians as
      well - that war strengthened humanity, people and races, physically and mentally.
      On the contrary, he argued, war is biologically counterproductive.

PMID- 28745248
TI  - [Diagnosis and treatment of orbital cellulitis].
AB  - Orbital cellulitis is a rare disease usually caused by sinusitis. Generally, the
      prognosis of both preseptal cellulitis and orbital cellulitis is favourable.
      Radiological distinction should be made between an orbital abscess and
      subperiosteal empyema. Theoretically, empyema is more accessible to antibiotics
      and, as it arises in a pre-existing anatomical space, it needs less aggressive
      treatment than an abscess. In contrast, the wall of an abscess created by the
      bacteria is scarcely permeable to antibiotics. Indications for surgical drainage
      should be based on clinical findings and not on Chandler's classification. Loss
      of vision, an unresponsive pupil or a densely packed orbit are indications for
      immediate surgical drainage. Drainage of an orbital abscess may speed up
      recovery.

PMID- 28745249
TI  - [A hardening in the forearm after an olecranon fracture].
AB  - A 77-year-old male who had had an olecranon fracture 15 years ago presented
      himself with mild pain of the right elbow. Physical examination revealed painless
      hardening of the finger and wrist flexors in an area of 10 cm from the origin.
      Conventional radiographs showed a mature myositis ossificans.

PMID- 28745250
TI  - [Recognising positional asphyxia: not always the cause of death in victims in an
      unusual position].
AB  - Deceased individuals may be found in a position that raises the question of
      whether or not the individual died from being in that position. We describe 3
      victims of 35, 84 and 54 years of age, respectively. All were found in an unusual
      position that may have impeded breathing. Breathing may be impaired by
      compression of the thoracic wall or by extrathoracic airway obstruction caused by
      the position. Reduced independence, with causes varying from dementia to
      inebriation, is a risk factor for positional asphyxia. Restraining a person in
      the so-called "hogtie position" does not lead to positional asphyxia. Positional
      asphyxiation in individuals dying in the hogtie position must not be confused
      with excited delirium syndrome (EDS). On the other hand, the diagnosis of
      positional asphyxia must be seriously considered in deceased individuals found in
      a position that may impede breathing.

PMID- 28745251
TI  - [Using thromboelastography to measure coagulation following massive blood loss].
AB  - Thromboelastography is becoming increasingly important for diagnosing coagulation
      disorders in patients with massive blood loss. This whole-blood measurement
      provides information about the speed of clot formation, clot strength, and degree
      of fibrinolysis. The result can be used as a basis for making a faster and better
      choice of a suitable blood product for the patient with severe blood loss. This
      technique can be carried out simply and quickly as a rapid test ('point-of-care
      test') or in a central laboratory. Use of thromboelastography in patients
      undergoing cardiac surgery results in reduced use of blood products and is proven
      to be cost effective. A reduction in the use of blood products was also seen in
      trauma patients and patients undergoing liver transplantation when this technique
      was used. Studies on other groups of patients with massive blood loss are being
      conducted at the moment.

PMID- 28745252
TI  - [Culturally sensitive communication in end-of-life care: the care for Muslim
      patients as an example].
AB  - Suffering and death are an inevitable part of life. In our increasingly
      multicultural society, healthcare professionals are frequently confronted with
      ideas on suffering and death that are different from their own. As Muslims are
      the largest migrant group in the Netherlands, this article focuses specifically
      on their perspective, illustrated by a clinical case. The different experience of
      these phenomena, influenced by culture and religion, can lead to confusion and
      frustration for patients, their relatives, and healthcare professionals alike. It
      is essential that healthcare professionals are aware of both their own views and
      those of the patient, and have some knowledge of other cultures and religions.
      Healthcare professionals can use cultural (self-)reflection and culturally
      sensitive communication, examples of which are provided in this article, to build
      mutual trust and understanding. This may improve the patient-physician
      relationship and may make end-of-life communication, complex as it will ever be,
      a little more comprehensive.

PMID- 28745253
TI  - [Gastrointestinal symptoms with meningococcal infection. Emergence of Neisseria
      meningitidis serogroup W.]
AB  - BACKGROUND: Meningococcal disease usually presents as meningitis and/or
      septicaemia, but can also present as pneumonia or arthritis. Since 2000, a
      worldwide increase in meningococcal disease is reported which is caused by a new
      virulent clone of serogroup W (MenW:cc11). This subtype is more likely to give an
      atypical clinical presentation and results in high mortality rates. CASE
      DESCRIPTION: A 68-year-old woman with polymyalgia rheumatica, managed with
      prednisone, developed an acute gastrointestinal syndrome of nausea, diarrhoea,
      vomiting, fever and chills. She presented at the Emergency Department and was
      admitted to intensive care for septic shock. Blood cultures revealed MenW:cc11
      infection. She received antibiotic treatment and left the hospital in good
      condition 8 days after admission. CONCLUSION: MenW:cc11 is associated with
      gastrointestinal symptoms and sepsis. Recognition of this atypical clinical
      presentation is important for a timely and adequate treatment and for antibiotic
      prophylaxis of family members and close contacts.

PMID- 28745254
TI  - [A man with abdominal pain and subsequently a periumbilical haematoma].
AB  - A 71-year-old male presented with periumbilical ecchymosis formed after acute
      onset of abdominal pain and near collapse. At the time of presentation the
      haematoma was the only symptom. Following a CT scan, the diagnosis of a contained
      rupture of an iliac artery aneurysm was made. The patient was successfully
      treated with an endovascular stent graft.

PMID- 28745255
TI  - [Zika virus and sexual transmission; when and for how long does one need to use a
      condom?]
AB  - - More evidence has become available concerning the sexual transmission of Zika
      virus and viral shedding in semen, which has led to the expansion of
      international guidelines for prevention of sexual transmission; Dutch guidelines
      have not been altered.- Internationally, the use of condoms during sex or sexual
      abstinence is advised for the duration of the pregnancy. Furthermore, when
      actively trying to conceive one should use a condom for six months.- In the Dutch
      guidelines, men who have visited a Zika virus epidemic area are advised to use a
      condom for 2 months upon return, irrespective of their partner possibly being
      pregnant or their wish to conceive.- Based on reports to the World Health
      Organisation and patient reports, the serial interval between disease onsets of
      both sexual partners is 4-44 days (median: 15).- Zika virus RNA is often no
      longer detectable in semen 2-3 months after disease onset.- International
      guidelines are based on the maximum detection period of Zika virus RNA and on
      virus isolation. Dutch prevention guidelines, on the other hand, are based on the
      longest serial interval known for sexual transmission (44 days).- Detection of
      Zika virus RNA in semen does not give a definitive answer on contagiousness.
      Currently, following the Dutch prevention advice is the best option in order to
      prevent sexual transmission.

PMID- 28745256
TI  - [Video recording and data collection in the operating room: the way to a 'just
      culture' in the OR].
AB  - The Academic Medical Center, Amsterdam, has started a trial to evaluate the
      usefulness to team debriefings of performance reports generated by a medical data
      recorder (MDR) in the operating room (OR). Outcome performance reports in
      structured debriefings in a secure, non-punitive environment are likely to
      heighten the level of situational awareness of OR teams. This may prevent future
      error. In addition, the use of video and - even more likely - use of an MDR may
      contribute to establishing a 'just culture' in the OR. MDRs offer a wealth of
      data, but only if these data are processed well do the resulting outcome reports
      reveal insights useful for structured debriefings. The implementation of video
      recordings or MDRs must be preceded by carefully addressing privacy and
      litigation issues relating to both OR staff and patients. In this article, we
      address viewpoints and discuss implementation strategy and the legal
      considerations involved in enabling the use of video and data registration in the
      OR.

PMID- 28745257
TI  - [Deciding on surgery for acute subdural haematoma; does a neurosurgeon rather
      fill nursing homes or cemeteries?]
AB  - Acute subdural haematoma is a life-threatening condition that can sometimes be
      mitigated by decompressive craniotomy. However, it can also increase misery when
      patients survive but are left with severe disabilities. A recent publication
      shows that neurosurgeons in Belgium and the Netherlands vary considerably in
      their opinion regarding if, and when, to perform this surgery. This may be due to
      the fact that this type of intervention asks the question whether the life saved
      is more favourable than the death averted. This requires a value judgement that
      has to be informed by the flawed and incomplete medical literature and by the
      perhaps even more flawed and incomplete (relayed) accounts of the wishes and
      attitudes of the unconscious patient. However, in the end, the surgeon also
      evaluates his own convictions in the whole issue and this will inevitably
      introduce subjectivity and practice variation. A structured moral debate may help
      to improve the extremely difficult decision-making process around the management
      of acute subdural haematoma.

PMID- 28745258
TI  - [A fact-free medicine? Report by Dutch Council for Public Health and Society is
      slap in the face].
AB  - A recently released report by the Dutch Council for Public Health and Society
      ('Raad voor Volksgezondheid en Samenleving') is subtitled "About the illusion of
      evidence-based practice in healthcare". The author argues that this report is a
      sign of the times, a period of "post-truth medicine" and "alternative facts", in
      which "science offers nothing but a reduction". Although the report rightly - but
      superfluously - argues that having an evidence base is insufficient for
      delivering quality care (no decisions without considering context), its depiction
      of the illusory nature of evidence-based practice represents a brutal slap in the
      face of all those who turn to sound clinical and biomedical research to back up
      or refute claims about the effectiveness of healthcare interventions.

PMID- 28745259
TI  - Serum and tissue 25-OH vitamin D3 concentrations do not predict bone
      abnormalities and molecular markers of vitamin D metabolism in the
      hypovitaminosis D kyphotic pig model.
AB  - The hypovitaminosis D kyphotic pig provides a model to study maternal vitamin D
      (D) carryover on gross and molecular characteristics of bone abnormalities in
      offspring. Excess maternal D is proposed to protect offspring under nutritional
      challenges from developing bone abnormalities. Relationships between D
      sufficiency parameters and bone abnormalities were characterised. Sows (n 37)
      were fed diets with 0 (-D), 8.125 (+D) or 43.750 (++D) ug D3/kg throughout
      gestation and lactation. At weaning (3 weeks) pigs were fed diets with 0 (-D) or
      7.0 (+D) ug D3/kg, each with 75 and 95 % (LCaP) or 150 and 120 % (HCaP) of the Ca
      and P requirements. Pigs were euthanised before colostrum consumption at birth (n
      27), 3 weeks (n 27) or after the nursery period (7 weeks, n 71) for tissue
      analysis. At 7 weeks, differences due to maternal D were detected (P<=0.05) in
      pig growth, serum parameters and mRNA expression regardless of nursery diet.
      Prevalence of kyphosis in pigs at 13 weeks was affected by maternal D, but not
      prevented by only HCaP or +D nursery diets. Increased (P<=0.05) serum 25-OH-D3
      concentrations in sows fed +D or ++D diets were not reflected by similar
      magnitudes of 25-OH-D3 in colostrum, 18-d milk, or serum and tissue
      concentrations in pigs. The mode of action by which maternal dietary D influences
      development of skeletal abnormalities warrants further investigation.

PMID- 28745261
TI  - Examining bidirectional relationships between parenting and child maladjustment
      in youth with autism spectrum disorder: A 9-year longitudinal study-CORRIGENDUM.

PMID- 28745260
TI  - Implementation of an Antimicrobial Stewardship Program in a Neonatal Intensive
      Care Unit.
AB  - OBJECTIVE To evaluate antimicrobial utilization and prescription practices in a
      neonatal intensive care unit (NICU) after implementation of an antimicrobial
      stewardship program (ASP). DESIGN Quasi-experimental, interrupted time-series
      study. SETTING A 54-bed, level IV NICU in a regional academic and tertiary
      referral center. PATIENTS AND PARTICIPANTS All neonates prescribed antimicrobials
      from January 1, 2011, to June 30, 2016, were eligible for inclusion. INTERVENTION
      Implementation of a NICU-specific ASP beginning July 2012. METHODS We convened a
      multidisciplinary team and developed guidelines for common infections, with a
      focus on prescriber audit and feedback. We conducted an interrupted time-series
      analysis to evaluate the effects of our ASP. Our primary outcome measure was days
      of antibiotic therapy (DOT) per 1,000 patient days for all and for select
      antimicrobials. Secondary outcomes included provider-specific antimicrobial
      prescription events for suspected late-onset sepsis (blood or cerebrospinal fluid
      infection at >72 hours of life) and guideline compliance. RESULTS Antibiotic
      utilization decreased by 14.7 DOT per 1,000 patient days during the stewardship
      period, although this decrease was not statistically significant (P=.669). Use of
      ampicillin, the most commonly antimicrobial prescribed in our NICU, decreased
      significantly, declining by 22.5 DOT per 1,000 patient days (P=.037). Late-onset
      sepsis evaluation and prescription events per 100 NICU days of clinical service
      decreased significantly (P<.0001), with an average reduction of 2.65 evaluations
      per year per provider. Clinical guidelines were adhered to 98.75% of the time.
      CONCLUSIONS Implementation of a NICU-specific antimicrobial stewardship program
      is feasible and can improve antibiotic prescribing practices. Infect Control Hosp
      Epidemiol 2017;38:1137-1143.

PMID- 28745262
TI  - Food advertising on Argentinean television: are ultra-processed foods in the
      lead?
AB  - OBJECTIVE: To describe the number of processed and ultra-processed food (PUPF)
      advertisements (ads) targeted to children on Argentinean television (TV), to
      analyse the advertising techniques used and the nutritional quality of the foods
      advertised, and to determine the potential exposure of children to unhealthy food
      advertising in our country. DESIGN: Five free-to-air channels and the three most
      popular children's cable networks were recorded from 07.00 to 22.00 hours for 6
      weeks. Ads were classified by target audience, type of product, advertised food
      categories and advertising strategies used. The NOVA system was used to classify
      food products according to industrial food processing level. Nutritional quality
      was analysed using the Pan American Health Organization's nutrient profile model.
      SETTING: Buenos Aires, Argentina. Results are considered applicable to most of
      the country. SUBJECTS: The study did not involve human subjects. RESULTS: Of the
      sample of food ads, PUPF products were more frequently advertised during
      children's programmes (98.9 %) v. programmes targeted to the general audience
      (93.7 %, chi 2=45.92, P<0.01). The top five food categories were desserts, dairy
      products, non-alcoholic sugary beverages, fast-food restaurants, and salty
      snacks. Special promotions and the appearance of cartoon characters were much
      more frequent in ads targeting children. Argentinean children are estimated to be
      exposed to sixty-one ads for unhealthy PUPF products per week. CONCLUSIONS: Our
      study showed that Argentinean children are exposed to a high number of unhealthy
      PUPF ads on TV. The Argentinean Government should build on this information to
      design and implement a comprehensive policy to reduce exposure to unhealthy food
      marketing that includes TV and other communication channels and places.

PMID- 28745263
TI  - Externalizing behavior severity in youths with callous-unemotional traits
      corresponds to patterns of amygdala activity and connectivity during judgments of
      causing fear-CORRIGENDUM.

PMID- 28745264
TI  - Shared genetic influences do not explain the association between parent-offspring
      relationship quality and offspring internalizing problems: results from a
      Children-of-Twins study.
AB  - BACKGROUND: Associations between parenting and child outcomes are often
      interpreted as reflecting causal, social influences. However, such associations
      may be confounded by genes common to children and their biological parents. To
      the extent that these shared genes influence behaviours in both generations, a
      passive genetic mechanism may explain links between them. Here we aim to quantify
      the relative importance of passive genetic v. social mechanisms in the
      intergenerational association between parent-offspring relationship quality and
      offspring internalizing problems in adolescence. METHODS: We used a Children-of
      Twins (CoT) design with data from the parent-based Twin and Offspring Study of
      Sweden (TOSS) sample [909 adult twin pairs and their offspring; offspring mean
      age 15.75 (2.42) years], and the child-based Swedish Twin Study of CHild and
      Adolescent Development (TCHAD) sample [1120 adolescent twin pairs; mean age 13.67
      (0.47) years]. A composite of parent-report measures (closeness, conflict,
      disagreements, expressions of affection) indexed parent-offspring relationship
      quality in TOSS, and offspring self-reported internalizing symptoms were assessed
      using the Child Behavior Checklist (CBCL) in both samples. RESULTS: A social
      transmission mechanism explained the intergenerational association [r = 0.21
      (0.16-0.25)] in our best-fitting model. A passive genetic transmission pathway
      was not found to be significant, indicating that parental genetic influences on
      parent-offspring relationship quality and offspring genetic influences on their
      internalizing problems were non-overlapping. CONCLUSION: These results indicate
      that this intergenerational association is a product of social interactions
      between children and parents, within which bidirectional effects are highly
      plausible. Results from genetically informative studies of parenting-related
      effects should be used to help refine early parenting interventions aimed at
      reducing risk for psychopathology.

PMID- 28745265
TI  - When the Rising Tide Impacts the World: Addressing the Global Challenge of
      Dementia.

PMID- 28745266
TI  - Adolescents from upper middle class communities: Substance misuse and addiction
      across early adulthood-CORRIGENDUM.

PMID- 28745267
TI  - Revisiting subcortical brain volume correlates of autism in the ABIDE dataset:
      effects of age and sex.
AB  - BACKGROUND: Autism spectrum disorders (ASD) are characterized by substantial
      clinical, etiological and neurobiological heterogeneity. Despite this
      heterogeneity, previous imaging studies have highlighted the role of specific
      cortical and subcortical structures in ASD and have forwarded the notion of an
      ASD specific neuroanatomy in which abnormalities in brain structures are present
      that can be used for diagnostic classification approaches. METHOD: A large (N =
      859, 6-27 years, IQ 70-130) multi-center structural magnetic resonance imaging
      dataset was examined to specifically test ASD diagnostic effects regarding
      (sub)cortical volumes. RESULTS: Despite the large sample size, we found virtually
      no main effects of ASD diagnosis. Yet, several significant two- and three-way
      interaction effects of diagnosis by age by gender were found. CONCLUSION: The
      neuroanatomy of ASD does not exist, but is highly age and gender dependent.
      Implications for approaches of stratification of ASD into more homogeneous
      subtypes are discussed.

PMID- 28745268
TI  - Assessing body image in anorexia nervosa using biometric self-avatars in virtual
      reality: Attitudinal components rather than visual body size estimation are
      distorted.
AB  - BACKGROUND: Body image disturbance (BID) is a core symptom of anorexia nervosa
      (AN), but as yet distinctive features of BID are unknown. The present study aimed
      at disentangling perceptual and attitudinal components of BID in AN. METHODS: We
      investigated n = 24 women with AN and n = 24 controls. Based on a three
      dimensional (3D) body scan, we created realistic virtual 3D bodies (avatars) for
      each participant that were varied through a range of +/-20% of the participants'
      weights. Avatars were presented in a virtual reality mirror scenario. Using
      different psychophysical tasks, participants identified and adjusted their actual
      and their desired body weight. To test for general perceptual biases in
      estimating body weight, a second experiment investigated perception of weight and
      shape matched avatars with another identity. RESULTS: Women with AN and controls
      underestimated their weight, with a trend that women with AN underestimated more.
      The average desired body of controls had normal weight while the average desired
      weight of women with AN corresponded to extreme AN (DSM-5). Correlation analyses
      revealed that desired body weight, but not accuracy of weight estimation, was
      associated with eating disorder symptoms. In the second experiment, both groups
      estimated accurately while the most attractive body was similar to Experiment 1.
      CONCLUSIONS: Our results contradict the widespread assumption that patients with
      AN overestimate their body weight due to visual distortions. Rather, they
      illustrate that BID might be driven by distorted attitudes with regard to the
      desired body. Clinical interventions should aim at helping patients with AN to
      change their desired weight.

PMID- 28745269
TI  - Hepatitis B virus prevents excessive viral production via reduction of cell death
      inducing DFF45-like effectors.
AB  - The relationship between hepatitis B virus (HBV) infection and lipid accumulation
      remains largely unknown. In this study, we investigated the effect of HBV
      propagation on lipid droplet growth in HBV-infected cells and HBV-producing cell
      lines, HepG2.2.15 and HBV-inducible Hep38.7-Tet. The amount of intracellular
      triglycerides was significantly reduced in HBV-infected and HBV-producing cells
      compared with HBV-lacking control cells. Electron and immunofluorescent
      microscopic analyses showed that the average size of a single lipid droplet (LD)
      was significantly less in the HBV-infected and HBV-producing cells than in the
      HBV-lacking control cells. Cell death-inducing DFF45-like effectors (CIDEs) B and
      C (CIDEB and CIDEC), which are involved in LD expansion for the improvement of
      lipid storage, were expressed at a significantly lower level in HBV-infected or
      HBV-producing cells than in HBV-lacking control cells, while CIDEA was not
      detected in those cells regardless of HBV production. The activity of the CIDEB
      and CIDEC gene promoters was impaired in HBV-infected or HBV-producing cells
      compared to HBV-lacking control cells, while CIDEs potentiated HBV core promoter
      activity. The amount of HNF4alpha, that can promote the transcription of CIDEB
      was significantly lower in HBV-producing cells than in HBV-lacking control cells.
      Knockout of CIDEB or CIDEC significantly reduced the amount of supernatant HBV
      DNA, intracellular viral RNA and nucleocapsid-associated viral DNA, while the
      expression of CIDEB or CIDEC recovered HBV production in CIDEB- or CIDEC-knockout
      cells. These results suggest that HBV regulates its own viral replication via
      CIDEB and CIDEC.

PMID- 28745270
TI  - Chromosomal and Nuclear Alterations in the Root Tip Cells of Vicia faba Induced
      by Sodium Chloride.
AB  - Despite the well-known toxic effect of chloride sodium (NaCl), only few studies
      analyze its genotoxic effect on crops. Micronucleus assay is an efficient tool
      for the measure of chromosomal DNA damages. Based on this test, the effects of
      salt on micronucleus induction, and on chromosome and nucleus changes, were
      investigated in Vicia faba root tips treated with NaCl (electrical conductivity =
      25 dS/m) during 24 hours. V. faba meristematic cells showed a significant
      increase in the number of micronuclei compared with the control. Micronucleus
      size varied from small to large and appeared at different stages of mitosis.
      Moreover, different chromosomal aberrations like breaks, bridges, rings, vagrant,
      and lagging chromosomes, were observed in the metaphase, the anaphase, and the
      telophase. In addition, nuclear alterations in the interphase were characterized
      by the presence of binucleated cells, strap nuclei with lesions, hyperchromasia,
      buds, and nuclei with irregular shapes and lesions.

PMID- 28745271
TI  - Nuclear domain 10 components upregulated via interferon during human
      cytomegalovirus infection potently regulate viral infection.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that causes life
      threatening disease in immunocompromised and immunonaive individuals. Type I
      interferons (IFNs) are crucial molecules in the innate immune response to HCMV
      and are also known to upregulate several components of the interchromosomal
      multiprotein aggregates collectively referred to as nuclear domain 10 (ND10). In
      the context of herpesvirus infection, ND10 components are known to restrict gene
      expression. This raises the question as to whether key ND10 components (PML,
      Sp100 and hDaxx) act as anti-viral IFN-stimulated genes (ISGs) during HCMV
      infection. In this study, analysis of ND10 component transcription during HCMV
      infection demonstrated that PML and Sp100 were significantly upregulated whilst
      hDaxx expression remained unchanged. In cells engineered to block the production
      of, or response to, type I IFNs, upregulation of PML and Sp100 was not detected
      during HCMV infection. Furthermore, pre-treatment with an IFN-beta neutralizing
      antibody inhibited upregulation of PML and Sp100 during both infection and
      treatment with HCMV-infected cell supernatant. The significance of ND10
      components functioning as anti-viral ISGs during HCMV infection was determined
      through knockdown of PML, Sp100 and hDaxx. ND10 knockdown cells were
      significantly more permissive to HCMV infection, as previously described but, in
      contrast to control cells, could support HCMV plaque formation following IFN-beta
      pre-treatment. This ability of HCMV to overcome the potently anti-viral effects
      of IFN-beta in ND10 expression deficient cells provides evidence that ND10
      component upregulation is a key mediator of the anti-viral activity of IFN-beta.

PMID- 28745272
TI  - Long Noncoding RNA HOTAIR: An Oncogene in Human Cervical Cancer Interacting With
      MicroRNA-17-5p.
AB  - Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are a class
      of significant regulators in various tumorigenesis processes. The lncRNA homeobox
      transcript antisense RNA (HOTAIR) has been reported to act as a functional lncRNA
      in cervical cancer development. The present study investigated the underlying
      mechanism of HOTAIR and miR-17-5p in cervical cancer tumorigenesis. The results
      showed that HOTAIR expression was significantly upregulated in both cervical
      cancer tissues and cell lines. Loss-of-function experiments showed that HOTAIR
      knockdown inhibited the proliferation, migration, and invasion of cervical cells.
      In addition, miR-17-5p expression was downregulated in cervical cancer tissues
      and cell lines. Pearson's correlation analysis indicated that miR-17-5p
      expression was negatively correlated to that of HOTAIR. Luciferase reporter assay
      revealed that miR-17-5p directly targeted HOTAIR 3'-UTR. Rescue experiments
      showed that miR-17-5p knockdown could reverse the tumor-suppressing effect caused
      by si-HOTAIR transfection. In summary, our results reveal the tumor-promoting
      role of HOTAIR in cervical cancer via sponging miR-17-5p, providing a novel
      therapeutic target for future treatment of cervical cancer.

PMID- 28745273
TI  - Performance and Kinetics of Nitrification of Low Ammonia Wastewater at Low
      Temperature.
AB  - The objective of this study was to investigate the effect of dissolved oxygen
      on nitrification in a sequencing batch reactor (SBR) treating low ammonia
      wastewater (40 mg N/L) at a low temperature (14  degrees C). During the 130 days
      of operation, three dissolved oxygen levels (5-6 mg dissolved oxygen/L, 2-3 mg
      dissolved oxygen/L, and 0.8-1.0 mg dissolved oxygen/L) were tested. Dissolved
      oxygen reduction resulted in lower ammonia oxidizing bacteria (AOB) and nitrite
      oxidizing bacteria (NOB) activity, with decreasing ammonia conversion ratio and
      increasing nitrite accumulation ratio. The maximum growth rates of AOB and NOB
      determined in this study (0.28 and 0.38 d-1) were below the median values from
      the literature (0.47 and 0.62 d-1), whereas the oxygen half-saturation
      coefficients of AOB and NOB (1.36 and 2.79 mg/L) were higher than those found in
      the literature. The kinetic model explained the SBR performance well. Low
      dissolved oxygen, together with long solids retention time, was recommended for
      partial nitrification at a low temperature.

PMID- 28745274
TI  - A Multivariate Analysis of the Composition and Properties of Extra Virgin Olive
      Oils Produced from Different Cultivars Grown in Iran.
AB  - The present study investigated variations in extra virgin olive oils in relation
      to fatty acid (FA) composition and the characteristics of 10 olive cultivars. The
      findings demonstrated that their oil yield properties, including refractive
      index, acid value, peroxide value, saponification value, iodine value, and
      composition, were significantly different. Moreover, based on GC-MS analysis, the
      presence of oleic acid [C18:1(9)] was identified as one of the major components.
      The highest amount of 18:1(9) was found in four major varieties of cultivars,
      namely Zard, Roghani, Karidolia, and Korfolia. Hierarchical cluster analysis of
      principal component analysis revealed two distinct categories of cultivars based
      on their FAs. The first category (cluster I), consisted of Arbequina, Karydolia,
      Roghani, and Zard cultivars, which can be considered cultivars with good
      commercial cultivation potential due to their high contents of unsaturated FAs
      and oil quantities produced.

PMID- 28745275
TI  - Hyaluronic Acid and Periodontitis.
AB  - Hyaluronic acid (HA; synonyms- Hyaluronan, Hyaluronate) is a glycosaminoglycan
      found in the connective tissue of vertebrates. It is the most abundant
      glycosaminoglycan of higher molecular weight in the extracellular matrix of soft
      periodontal tissues. The use of HA in the treatment of inflammatory process is
      established in medical areas such as orthopedics, dermatology and ophthalmology.
      In the field of dentistry, it has shown anti-inflammatory and anti-bacterial
      effects in gingivitis and periodontitis therapy. Due to its tissue healing
      properties, it could be used as an adjunct to mechanical therapy in the treatment
      of periodontitis.

PMID- 28745276
TI  - Surface Activation Leukocyte Markers and Humoral Factors in Cord Blood of
      Newborns at Risk of Early Infection.
AB  - Due to immaturity of both specific and non-specific immune mechanisms, neonates
      are at risk of serious infections. The risk group definition is vague, clinical
      signs are non-specific and common laboratory markers are not as useful as in
      later ages, especially due to delayed reactions. In an attempt to find early,
      sensitive and specific markers, we assessed a defined set of surface leukocyte
      markers and humoral factors in cord blood. Several differences were noted -
      children in the risk group had a higher proportion of CD19+/23+, CD16+/64+,
      CD45RO cells and higher levels of IL-6. We find it promising that already at
      birth there are notable signs of reaction to infection and that a follow-up of a
      set of infectious markers could be useful to identify the children in need of
      antibiotic treatment and for diminishing unnecessary treatment.

PMID- 28745277
TI  - The Inflammatory Radicular Cysts Have Higher Concentration of TNF-alpha in
      Comparison to Odontogenic Keratocysts (Odontogenic Tumour).
AB  - TNF-alpha is a pleiotropic cytokine that is considered as a primary modifier of
      inflammatory and immune reaction in response to various inflammatory diseases and
      tumour. We investigated levels of TNF-alpha in 43 radicular cysts and 15
      odontogenic keratocysts, obtained from patients undergoing surgery, under local
      anaesthesia, and after aspiration of cystic fluid from non-ruptured cysts. TNF
      alpha is elevated in both cysts' fluid, but higher values were found in radicular
      cysts in comparison to keratocysts. The significantly higher concentration of TNF
      alpha was associated with smaller radicular cysts, higher protein concentration,
      higher presence of inflammatory cells in peri cystic tissues, and the degree of
      vascularisation and cysts wall thickness (Mann-Whitney U-test, p<0.05). No
      correlation was found based on these parameters in odontogenic keratocyst, but
      all cysts have detectable concentrations of TNF-alpha. We here for the first time
      present that a difference in the concentration of TNF-alpha exists between these
      two cystic types.

PMID- 28745278
TI  - Amperometric Biosensor for Pesticide Methamidophos Assay.
AB  - Amperometric biosensor based on enzyme acetylcholinesterase (AChE; EC 3.1.1.7)
      was tested for pesticide methamidophos assay. Biosensor consists from four screen
      printed platinum electrodes on ceramic strip. AChE was physically adsorbed onto
      the electrode surface. The measuring principle was based on the inhibition of
      AChE activity in the presence of methamidophos. The proposed method limit of
      detection was 2.45 nM, responding to 3.46 pg of methamidophos detected absolutely
      when we consider the sample volume.

PMID- 28745279
TI  - Paediatric nanofibrous bioprosthetic heart valve.
AB  - The search for an optimal aortic valve implant with durability, calcification
      resistance, excellent haemodynamic parameters and ability to withstand mechanical
      loading is yet to be met. Thus, there has been struggled to fabricate bio
      prosthetics heart valve using bioengineering. The consequential product must be
      resilient with suitable mechanical features, biocompatible and possess the
      capacity to grow. Defective heart valves replacement by surgery is now common,
      this improves the value and survival of life for a lot of patients. The recent
      paediatric heart valve implant is suboptimal due to their inability of somatic
      growth. They usually have multiple surgeries to change outgrown valves. Short
      lived valve bio-prostheses occurring in older patients and younger ones who more
      usually need the replacement of its damaged heart with prosthesis led to a new
      invasive surgical interventions with an improved quality of life. The authors
      propose that nanofibre scaffold for paediatric tissue-engineered heart valve will
      meet most of these conditions, most particularly those related to somatic growth,
      and, as the nanofibre scaffold is eroded, new valve is produced, the valve
      matures in the child until adulthood.

PMID- 28745280
TI  - Antimicrobial properties of nanorods: killing bacteria via impalement.
AB  - Silver is known to possess anti-microbial properties that are of chemical origin.
      It is believed that either Ag atoms bind to thiol groups in bacterial enzymes or
      Ag+ ions enter bacterial cells and denature the DNA molecule to kill bacteria.
      Silver nanorods, however, may kill bacteria by another mechanism: it is possible
      that the sharp tips of the nanorods puncture bacterial cells and kill bacteria
      via impalement-a physical mechanism. To test if this can indeed happen, we have
      compared the anti-microbial properties of silver and CdS nanorods. No significant
      difference is found between the two even though CdS does not possess the chemical
      properties of silver. This indicates that the physical kill mechanism is indeed
      likely and therefore nanorods of any material may possess anti-microbial
      properties. In that case, it is possible to overcome serious short- and long-term
      health hazard issues which have been posed by silver nanoparticles by replacing
      them with nanorods of innocuous elements or compounds. A surface containing
      nanorods of varying heights presents an undulating bed of spikes to microbes and
      is most inhospitable to bacteria.

PMID- 28745281
TI  - Antibacterial potential of silver nanoparticles biosynthesised using Canarium
      ovatum leaves extract.
AB  - Silver nanoparticles (AgNPs) have been extensively used as antibacterial agents,
      owing to their ease of preparation. In the present study, leaves extract of
      Canarium ovatum have been employed for the biosynthesis of silver nanoparticles
      (CO-AgNPs). CO-AgNPs were synthesised under very mild, eco-friendly manner where
      the plant extract acted both as reducing and capping agent. These AgNPs were
      synthesised by taking into account several parameters, that included, time of
      reaction, concentration of AgNO3, amount of extract and temperature of reaction.
      The optimisation studies suggested efficient synthesis of CO-AgNPs at 25 degrees
      C when 1.5 mM AgNO3 was reduced with 1:20 ratio of plant extract for 40 min. Size
      determination studies done on dynamic light scattering and scanning electron
      microscope suggested of spherical shape nanoparticles of size 119.7 +/- 7 nm and
      50-80 nm, respectively. Further, characterisations were done by Fourier transform
      infrared and energy-dispersive X-ray spectroscopy to evaluate the functional
      groups and the purity of CO-AgNPs. The antibacterial efficacy of CO-AgNPs was
      determined against the bacterial strain Pseudomonas aeruginosa. As evident from
      disc diffusion method studies, CO-AgNPs remarkably inhibited the growth of the
      tested microorganism. This study suggested that C. ovatum extract efficiently
      synthesises CO-AgNPs with significant antibacterial properties and can be good
      candidates for therapeutics.

PMID- 28745282
TI  - Methanobactin-mediated synthesis of bimetallic Au-Pd/Al2O3 toward an efficient
      catalyst for glucose oxidation.
AB  - A green bioreductive approach with methanobactin was adopted to fabricate
      bimetallic Au-Pd/Al2O3 catalysts for solvent-free oxidation of glucose to
      gluconic acid with H2O2 at atmospheric pressure. The catalyst was characterised
      by diffuse reflectance UV-vis spectroscopy, transmission electron microscopy, X
      ray photoelectron spectroscopy, and X-ray diffraction techniques to understand
      synergistic interactions between Au and Pd. Effects of Au to Pd molar ratio on
      the catalytic activity of Au-Pd/Al2O3 were investigated. The Au-Pd/Al2O3 catalyst
      with Au/Pd molar ratio of 0.8:0.2 exhibited excellent catalytic performance. With
      the catalyst, the oxidation activities of glucose to gluconic acid 2856 mmol min
      1 g-1 and selectivity 99.6% were attained at 323 K with H2O2. The results
      indicated the activity and selectivity was affected by the ratio of Au/Pd on the
      Al2O3. The formation of Au0.8Pd0.2/Al2O3 was favourable for the catalytic
      reaction.

PMID- 28745283
TI  - Fabrication of biopolymer based nanocomposite wound dressing: evaluation of wound
      healing properties and wound microbial load.
AB  - The aim of this study is to introduce natural-based polymers, chitosan and
      starch, to design a remedial nanocomposite, comprising of cerium oxide
      nanoparticles and silver nanoparticles, to investigate their effects in
      accelerating wound healing and in wound microbial load. Cerium oxide
      nanoparticles synthesized in starch solution added to the colloidal dispersion of
      synthesized silver nanoparticles in chitosan to make a three-component
      nanomaterial. Mice were anaesthetized and two parallel full-thickness round
      wounds were excised under aseptic conditions with the help of sterile dermal
      biopsy punch. Furthermore, effects of silver-chitosan and silver-cerium-chitosan
      nanocomposite had evaluated on rate of wound closure and collagen density and on
      microbial load of wound in full-thickness model. Results showed that both silver
      chitosan and silver-cerium-chitosan had significant impact on acceleration of
      wound closure and collagen content and on reduction of wound microbial load in
      comparison with control group, which was, received no treatments. However, the
      silver-cerium-chitosan nanocomposite is more potent than silver-chitosan group
      and control group in wound closure. The wound healing effects of silver-cerium
      chitosan nanocomposite are due to unique features of its three components and
      this nanocomposite promises impressive remedies for clinical application.

PMID- 28745284
TI  - Green synthesis of gold nanoparticles using Citrus maxima peel extract and their
      catalytic/antibacterial activities.
AB  - The peel of Citrus maxima (C. maxima) is the primary byproducts during the
      process of fruit or juice in food industries, and it was always considered as
      biomass waste for further treatments. In this study, the authors reported a
      simple and eco-friendly method to synthesise gold nanoparticles (AuNPs) using C.
      maxima peel extract as reducing and capping agents. The synthesised AuNPs were
      characterised by UV-visible spectrum, X-ray diffraction (XRD), transmission
      electron microscope (TEM) and Fourier-transform infrared spectroscopy (FTIR). The
      UV-visible spectrum of the AuNPs colloid showed a characteristic peak at 540 nm.
      The peaks of XRD analysis at (2theta) 38.30 degrees , 44.28 degrees , 64.62
      degrees , 77.57 degrees  and 81.75 degrees  were assigned to (111), (200), (220),
      (311) and (222) planes of the face-centered cubic (fcc) lattice of gold. The TEM
      images showed that AuNPs were nearly spherical in shape with the size of 8-25 nm.
      The FTIR spectrum revealed that some bioactive compounds capped the surface of
      synthesised AuNPs. The biosynthesised AuNPs performed strong catalytic activity
      in degradation of 4-nitrophenol to 4-aminophenol and good antibacterial activity
      against both gram negative (Escherichia coli) and gram positive (Staphylococcus
      aureus) bacterium. The synthesis procedure was proved simple, cost effective and
      environment friendly.

PMID- 28745285
TI  - Biosynthesised silver nanoparticles using aqueous leaf extract of Tagetes patula
      L. and evaluation of their antifungal activity against phytopathogenic fungi.
AB  - In the recent decades, nanotechnology is gaining tremendous impetus due to its
      capability of modulating metals into their nanosize, which drastically changes
      the chemical, physical, biological and optical properties of metals. In this
      study, silver nanoparticles (AgNPs) synthesis using aqueous leaf extracts of
      Tagetes patula L. which act as reducing agent as well as capping agent is
      reported. Synthesis of AgNPs was observed at different parameters like
      temperature, concentration of silver nitrate, leaf extract concentration and time
      of reduction. The AgNPs were characterized using UV-vis spectroscopy, scanning
      electron microscope with energy dispersive spectroscopy, transmission electron
      microscopy with selected area electron diffraction, X-ray diffraction, Fourier
      transform infrared and dynamic light scattering analysis. These analyses revealed
      the size of nanoparticles ranging from 15 to 30 nm as well revealed their
      spherical shape and cubic and hexagonal lattice structure. The lower zeta
      potential (-14.2mV) and the FTIR spectra indicate that the synthesized AgNPs are
      remarkably stable for a long period due to the capped biomolecules on the surface
      of nanoparticles. Furthermore, these AgNPs were found to be highly toxic against
      phytopathogenic fungi Colletotrichum chlorophyti by both in vitro and in vivo and
      might be a safer alternative to chemical fungicides.

PMID- 28745286
TI  - In situ green synthesis of Cu nanoparticles supported on natural Natrolite
      zeolite for the reduction of 4-nitrophenol, congo red and methylene blue.
AB  - This study demonstrates a clean, non-toxic and environment friendly synthetic
      strategy for the preparation of the Natrolite zeolite/Cu nanoparticles (NPs)
      using Natrolite zeolite as a natural support and Anthemis xylopoda flowers
      aqueous extract as a reducing and stabilising agent for the synthesis of Cu NPs.
      Cu NPs with 20 nm diameter were immobilised homogeneously on the surface of
      Natrolite zeolite. The synthesised Natrolite zeolite/Cu NPs was used as an
      environmentally benign catalyst for the reduction of 4-nitrophenol, congo red and
      methylene blue in aqueous media at an ambient temperature. It has been found that
      the catalyst can be reused several times without any decrease in activity.

PMID- 28745287
TI  - Copper nanoflowers as effective antifungal agents for plant pathogenic fungi.
AB  - Flower-shaped copper nanoparticles were synthesised by a green and ecofriendly
      chemical reduction approach using copper sulphate and cytyltrimethal ammonium
      bromide. The UV-vis spectrophotometer analysis showed maximum absorption at about
      552 nm, which is specifically reported for copper nanoparticles. The crystal
      lattice structure of copper nanoflowers was confirmed by X-ray diffraction
      analysis. Further, the transmission electron microscopic studies revealed the
      flower shape copper nanoparticles in the size range of 100-500 nm. The stability
      of thus synthesised copper nanoflowers was assessed by zeta potential analysis,
      which was found to be 35 mV indicating the most stable nature of nanoflowers. The
      antifungal activity of these copper nanoflowers was evaluated by Kirby-Bauer disk
      diffusion method against selected common plant pathogenic fungi. It was found
      that the chemosynthesised copper nanoflowers demonstrated significant inhibitory
      activity against the plant pathogenic Aspergillus niger, Fusarium moniliforme, F.
      culmorum, F. oxysporum and F. tricinctum. The maximum antifungal activity was
      shown against A. niger followed by F. moniliforme, F. oxysporum and F.
      tricinctum, whereas the minimum activity was reported against F. culmorum.
      Similarly, the effect of the copper nanoflowers was also evaluated in combination
      with commercial antifungal agent (ketoconazole), which demonstrated the enhanced
      activity of antifungal agent.

PMID- 28745288
TI  - Production, stabilisation and characterisation of silver nanoparticles coated
      with bioactive polymers pluronic F68, PVP and PVA.
AB  - The increasing and alarming panorama of bacterial infections and associated
      morbidities that occur during medical and hospital procedures makes the
      development of technologies that aid in controlling such bacterial infections of
      utmost importance. Recent studies have shown that formulations with metal
      nanoparticles exhibit good antibacterial properties against a broad spectrum of
      microorganisms. Moreover, it was demonstrated that some biologically active
      polymeric materials, when applied in combination with chemical antimicrobial
      agents, enhance the therapeutic action of the latter. The research effort
      entertained herein aimed at the physico-chemical characterisation of silver
      nanoparticles obtained by chemical reduction, stabilised by bioactive polymers
      polyvinyl alcohol and polyvinylpyrrolidone, and further co-stabilised by pluronic
      F68. Scanning electron microscopy images of the nanoparticles produced, coated
      with different stabilisers, have shown that the chemical nature of the
      stabilisation effect promoted incorporation of pluronic in the nanoparticles and
      was closely related to an increase in the silver concentration in the
      nanoparticle samples obtained via energy-dispersive X-ray spectroscopy. The study
      described herein also shows that the nature of the stabiliser favours the
      interaction of pluronic F68 with samples containing silver nanoparticles.

PMID- 28745289
TI  - Biosynthesis and characterisation of nano-silica as potential system for carrying
      streptomycin at nano-scale drug delivery.
AB  - A growing trend within nanomedicine has been the fabrication of self-delivering
      supramolecular nanomedicines containing a high and fixed drug content ensuring
      eco-friendly conditions. This study reports on green synthesis of silica
      nanoparticles (Si-NPs) using Azadirachta indica leaves extract as an effective
      chelating agent. X-ray diffraction analysis and Fourier transform-infra-red
      spectroscopic examination were studied. Scanning electron microscopy analysis
      revealed that the average size of particles formed via plant extract as reducing
      agent without any surfactant is in the range of 100-170 nm while addition of
      cetyltrimethyl ammonium bromide were more uniform with 200 nm in size.
      Streptomycin as model drug was successfully loaded to green synthesised Si-NPs,
      sustain release of the drug from this conjugate unit were examined. Prolong
      release pattern of the adsorbed drug ensure that Si-NPs have great potential in
      nano-drug delivery keeping the environment preferably biocompatible, future
      cytotoxic studies in this connection is helpful in achieving safe mode for nano
      drug delivery.

PMID- 28745290
TI  - Bacterial detection based on polymerase chain reaction and microbead
      dielectrophoresis characteristics.
AB  - In this study, an electrical DNA detection method was applied to bacterial
      detection. DNA was extracted from bacteria and amplified by polymerase chain
      reaction. The microbeads were labelled with amplicons, altering their surface
      conductance and therefore their dielectrophoresis characteristics. Amplicon
      labelled microbeads could thus be trapped within a high-strength electric field,
      where they formed a pearl chain between the electrodes, resulting in an increased
      conductance between the electrodes. This method reduces the amplicon detection
      time from 1-2 h to 15 min, compared with the conventional method. The presented
      method realised quantitative detection of specific bacteria at concentrations
      above 1 * 105 and 2.4 * 104 CFU/ml for bacterial solutions with and without other
      bacterial presence, respectively.

PMID- 28745291
TI  - Biogenic fabrication of CuNPs, Cu bioconjugates and in vitro assessment of
      antimicrobial and antioxidant activity.
AB  - In the present study, the authors synthesised copper nanoparticles (CuNPs) by
      using extract of Zingiber officinale (ginger) and later the NPs were
      bioconjugated with nisin, which shows antimicrobial activity against food
      spoilage microorganisms. CuNPs and its bioconjugate were characterised by
      ultraviolet-vis spectroscopy, NP tracking analysis, Zetasizer, transmission
      electron microscopy analysis, X-ray diffraction and Fourier transform infra-red
      (FTIR) spectroscopy. Zeta potential of CuNPs and its bioconjugate were found to
      be very stable. They evaluated in vitro efficacy of CuNPs and its bioconjugate
      against selected food spoilage bacteria: namely, Staphylococcus aureus,
      Pseudomonas fluorescens, Listeria monocytogenes and fungi including Fusarium
      moniliforme and Aspergillus niger. Antimicrobial activity of CuNPs was found to
      be maximum against F. moniliforme (18 mm) and the least activity was noted
      against L. monocytogenes (13 mm). Antioxidant activity of CuNPs and ginger
      extract was performed by various methods such as total antioxidant capacity
      reducing power assay, 1-1-diphenyl-2-picryl-hydrazyl free radical scavenging
      assay and hydrogen peroxide assay. Antioxidant activity of CuNPs was higher as
      compared with ginger extract. Hence, CuNPs and its bioconjugate can be used
      against food spoilage microorganisms.

PMID- 28745292
TI  - Biomimetic synthesis of AgNPs from Penicillium chrysogenum strain FGCC/BLS1 by
      optimising physico-cultural conditions and assessment of their antimicrobial
      potential.
AB  - Biomimetic synthesis of metal nanoparticles (NPs) is safe and eco-friendly;
      therefore, find diverse applications. Considering this, the soil fungi
      Penicillium chrysogenum strain Fungal germplasm collection centre/ BLS1 was
      isolated, characterized and explored to synthesize extracellular silver NPs
      (AgNPs) under optimised conditions. The synthesis of AgNPs was investigated using
      ultraviolet (UV)-visible spectroscopy, Fourier-transform infra-red spectroscopy
      (FTIR), transmission electron microscope (TEM) and dynamic light scattering (DLS)
      analysis. Process optimisation exhibited AgNPs synthesis within 8 h using 2 mM
      AgNO3 at pH 11 and temperature 70 degrees C. TEM analysis revealed polydispersed
      ellipsoidal shaped AgNPs with average particle size 96.8 nm as measured by DLS.
      AgNPs showed negative zeta potential that confers surface stability in solution.
      FTIR spectra confirmed the presence of protein bound to AgNPs. Antibacterial
      activity against Escherichia coli, Klebsiella pneumoniae and Staphylococcus
      aureus by the AgNPs (100 ppm) was demonstrated by counting colony forming unit ,
      disc diffusion, and growth kinetics assay. Additionally radial assay revealed
      antifungal activity of AgNPs (100 ppm) against phytopathogenic fungi Sclerotinia
      sclerotiorum Microbial type culture collection 8785. Furthermore, AgNPs (100 ppm)
      did not show any cytotoxic effects on human Red blood cells. Therefore, this
      novel fungal strain can be utilised for biofabrication of AgNPs under optimised
      conditions and have shown strong antimicrobial property.

PMID- 28745293
TI  - Biosynthesis of silver nanoparticles by Pseudomonas spp. isolated from effluent
      of an electroplating industry.
AB  - The aim of this study was to isolate and screen bacteria from soil and effluent
      of electroplating industries for the synthesis of silver nanoparticles and
      characterize the potential isolate. Soil and effluent of electroplating
      industries from Mumbai were screened for bacteria capable of synthesizing silver
      nanoparticles. From two soils and eight effluent samples 20 bacterial isolates
      were obtained, of these, one was found to synthesize silver nanoparticles.
      Synthesis of silver nanoparticle by bacteria was confirmed by undertaking
      characterization studies of nanoparticles that involved spectroscopy and electron
      microscopic techniques. The potential bacteria was found to be Gram-negative
      short rods with its biochemical test indicating Pseudomonas spp. Molecular
      characterization of the isolate by 16S r DNA sequencing was carried out which
      confirmed its relation to Pseudomonas hibiscicola ATCC 19867. Stable
      nanoparticles synthesized were 50 nm in size and variable shapes as seen in SEM
      micrographs. The XRD and FTIR confirmed the crystalline structure of
      nanoparticles and presence of biomolecules mainly proteins as agents for
      reduction and capping of nanoparticles. The study demonstrates synthesis of
      nanoparticles by bacteria from effluent of electroplating industry. This can be
      used for large scale synthesis of nanoparticles by cost effective and
      environmentally benign mode of synthesis.

PMID- 28745294
TI  - Controllable synthesis and characterisation of palladium (II) anticancer complex
      loaded colloidal gelatin nanoparticles as a novel sustained-release delivery
      system in cancer therapy.
AB  - Over the past few years, there have been several attempts to deliver anticancer
      drugs into the body. It has been shown that compared to other available carriers,
      colloidal gelatin nanoparticles (CGNPs) have distinct properties due to their
      exceptional physico-chemical and biological characteristics. In this study, a
      novel water-soluble palladium (II) anticancer complex was first synthesised, and
      then loaded into CGNPs. The CGNPs were synthesised through a two-step desolvation
      method with an average particle size of 378 nm. After confirming the stability of
      the drug in the nanoparticles, the drug-loaded CGNPs were tested for in vitro
      cytotoxicity against human breast cancer cells. The results showed that the
      average drug encapsulating efficiency and drug loading of CGNPs were 64 and 10 +/
      2.1% (w/w), respectively. There was a slight shift to higher values of
      cumulative release, when the samples were tested in lower pH values. In addition,
      the in vitro cytotoxicity test indicated that the number of growing cells
      significantly decreased after 48 h in the presence of different concentrations of
      drug. The results also demonstrated that the released drug could bind to DNA by a
      static mechanism at low concentrations (0.57 uM) on the basis of hydrophobic and
      hydrogen binding interactions.

PMID- 28745295
TI  - Determination of heavy metals in skin-whitening cosmetics using microwave
      digestion and inductively coupled plasma atomic emission spectrometry.
AB  - In this study, the determination of noxious heavy metals, cadmium (Cd), bismuth
      (Bi), mercury (Hg), titanium (Ti), lead (Pb) and metalloid arsenic (As) in skin
      whitening cosmetics were examined using microwave digestion and inductively
      coupled plasma atomic emission spectrometry method. A complete digestion of
      cosmetics samples was achieved using a mixture of hydrofluoric acid/hydrogen
      peroxide/nitric acid. The quantification of the target compounds was done by
      standard addition method. The excellent quality parameters for instance,
      detection limits, As (4.6 ppb), Bi (7.9 ppb), Cd (0.45 ppb), Hg (3.3 ppb), Pb
      (3.8 ppb), Ti (4.3 ppb), linearity (r2 > 0.999) and run-to-run and day-to-day
      precisions with relative standard deviations <3% were obtained. The recovery
      rates for standard reference materials were found between 90 and 105%. The
      average concentration of heavy metals in cosmetics samples were in the range of
      1.0-12.3 (MUg g-1, As), 33-7097 (MUg g-1, Bi), 0.20-0.6 (MUg g-1, Cd), 0.70-2700
      (MUg g-1, Hg), 1.20-143 (MUg g-1, Pb) and 2.0-1650 (MUg g-1, Ti).

PMID- 28745296
TI  - BBN conjugated GNPs: a new targeting contrast agent for imaging of breast cancer
      in radiology.
AB  - Using of targeted contrast agents in X-ray imaging of breast cancer can improve
      the accuracy of diagnosis, staging, and treatment planning by providing early
      detection and superior definition of tumour volume. This study demonstrates a new
      class of X-ray contrast agents based on gold nanoparticles (GNPs) and bombesin
      (BBN) for imaging of breast cancer in radiology. GNPs were synthesised in
      spherical shape in the size range of 15 +/- 2 nm and conjugated with BBN followed
      by coating with polyethyleneglycol (PEG). The in vitro and in vivo behaviour of
      PEG-coated GNPs-BBN conjugate was investigated performing cytotoxicity, binding,
      and internalisation assays as well as biodistribution and X-ray imaging studies
      in mouse bearing breast tumour. Cytotoxicity study showed biocompatibility of the
      prepared bioconjugate. The binding and internalisation studies using T47D cell
      line approved the targeting ability of new agent. The biodistribution study
      showed the considerable accumulation of prepared conjugate in breast tumour in
      mouse model. The breast tumour was clearly visualised in X-ray images taken from
      the mouse model. The results showed the potential of PEG-coated GNPs-BBN
      conjugate as a contrast agent in X-ray imaging of breast tumour in humans that
      need further investigations.

PMID- 28745297
TI  - Foley catheters functionalised with a synergistic combination of antibiotics and
      silver nanoparticles resist biofilm formation.
AB  - Foley catheters are inevitable in health care unit. Pathogens colonise and form
      biofilm on catheter causing catheter-associated urinary tract infection.
      Therefore, the authors aimed to functionalise catheter to resist biofilm
      formation. The authors impregnated urinary catheters with a synergistic
      combination of antibiotics and silver nanoparticles (SNPs) to evaluate
      antibiofilm efficacy in vitro and in vivo. SNPs were synthesised using Spirulina
      platensis. Synergy between the SNPs and antibiotics was determined by the checker
      board method. In vivo efficacy of the functionalised catheters was assessed in
      mice. Liver and kidney function tests of mice were performed. The in vitro anti
      adherence activity of the functionalised catheters was evaluated after 2 years.
      Nanoparticle sizes were 42-75 nm. Synergistic activity was observed among SNPs (2
      ug/ml), amikacin (6.25 ug/ml), and nitrofurantoin (31.25 ug/ml). In mice,
      catheters functionalised with combinations of antibiotics and SNPs exhibited no
      colonisation until Day 14. Blood, liver, and kidney tests were normal. After 2
      years, catheters functionalised with antibiotics exhibited 25% inhibition of
      bacterial adhesion, and catheters functionalised with the nanoparticle-antibiotic
      combination exhibited 90% inhibition. Impregnation of urinary catheters with a
      synergistic combination of antibiotics and SNPs is an efficient and promising
      method for preventing biofilm formation.

PMID- 28745298
TI  - Gender differences in severity of desaturation events following hypopnea and
      obstructive apnea events in adults during sleep.
AB  - OBJECTIVE: Severity estimation of obstructive sleep apnea (OSA) is currently
      based on the apnea-hypopnea index (AHI), which ignores individual breathing
      cessation event characteristics. Gender differences in the relationship between
      the breathing cessation event duration and the related desaturation event
      severity could mean that the severity of OSA is different in males and females
      despite a similar AHI. The aim of this work was to evaluate gender differences in
      the severity of peripheral oxygen desaturation events following obstructive
      apneas or hypopneas. APPROACH: Type I polysomnographic recordings of 220 males
      and 175 females were analyzed. The obstructive apnea and hypopnea events were
      divided into eight different durational categories from 10 s to 45 s with 5 s
      interval and  >45 s. The desaturation event severities following obstructive
      apneas or hypopneas were compared between genders within these durational
      categories. MAIN RESULTS: Desaturations following obstructive apneas with a
      duration of 30-45 s were substantially more severe (p  <  0.05) in females
      compared to males. In contrast, areas of desaturations following hypopneas (with
      related hypopnea event durations  ?30 s) were smaller (p  <  0.05) in females
      compared to males. In general, desaturation events following obstructive apneas
      were more severe compared to desaturations following hypopneas and the increase
      in the duration of obstructive apnea and hypopnea events led to an increase in
      the related desaturation severity in both genders. SIGNIFICANCE: We found gender
      differences in the desaturation event severities following obstructive apneas and
      hypopneas. The results indicate that in females longer obstructive apneas (>30 s)
      could be more detrimental compared to those of males. As severe health
      consequences are related to the desaturation severity these aspects should be
      considered when estimating the severity of OSA.

PMID- 28745299
TI  - Inferring imagined speech using EEG signals: a new approach using Riemannian
      manifold features.
AB  - OBJECTIVE: In this paper, we investigate the suitability of imagined speech for
      brain-computer interface (BCI) applications. APPROACH: A novel method based on
      covariance matrix descriptors, which lie in Riemannian manifold, and the
      relevance vector machines classifier is proposed. The method is applied on
      electroencephalographic (EEG) signals and tested in multiple subjects. MAIN
      RESULTS: The method is shown to outperform other approaches in the field with
      respect to accuracy and robustness. The algorithm is validated on various
      categories of speech, such as imagined pronunciation of vowels, short words and
      long words. The classification accuracy of our methodology is in all cases
      significantly above chance level, reaching a maximum of 70% for cases where we
      classify three words and 95% for cases of two words. SIGNIFICANCE: The results
      reveal certain aspects that may affect the success of speech imagery
      classification from EEG signals, such as sound, meaning and word complexity. This
      can potentially extend the capability of utilizing speech imagery in future BCI
      applications. The dataset of speech imagery collected from total 15 subjects is
      also published.

PMID- 28745300
TI  - On robust parameter estimation in brain-computer interfacing.
AB  - OBJECTIVE: The reliable estimation of parameters such as mean or covariance
      matrix from noisy and high-dimensional observations is a prerequisite for
      successful application of signal processing and machine learning algorithms in
      brain-computer interfacing (BCI). This challenging task becomes significantly
      more difficult if the data set contains outliers, e.g. due to subject movements,
      eye blinks or loose electrodes, as they may heavily bias the estimation and the
      subsequent statistical analysis. Although various robust estimators have been
      developed to tackle the outlier problem, they ignore important structural
      information in the data and thus may not be optimal. Typical structural elements
      in BCI data are the trials consisting of a few hundred EEG samples and indicating
      the start and end of a task. APPROACH: This work discusses the parameter
      estimation problem in BCI and introduces a novel hierarchical view on robustness
      which naturally comprises different types of outlierness occurring in structured
      data. Furthermore, the class of minimum divergence estimators is reviewed and a
      robust mean and covariance estimator for structured data is derived and evaluated
      with simulations and on a benchmark data set. MAIN RESULTS: The results show that
      state-of-the-art BCI algorithms benefit from robustly estimated parameters.
      SIGNIFICANCE: Since parameter estimation is an integral part of various machine
      learning algorithms, the presented techniques are applicable to many problems
      beyond BCI.

PMID- 28745301
TI  - Automatic detection of T wave alternans using tensor decompositions in multilead
      ECG signals.
AB  - OBJECTIVE: T wave alternans (TWA) is a promising non-invasive risk stratification
      tool for sudden cardiac death which can be detected from surface ECG. This paper
      proposes a novel method to automatically detect TWA based on tensor decomposition
      methods. APPROACH: Two different tensor decomposition approaches are examined and
      compared, namely canonical polyadic decomposition and the more generalized
      variation PARAFAC2 which allows the T waves to shift in time. RESULTS AND
      SIGNIFICANCE: Results on different artificial and clinical signals show that the
      presented methods are a robust and reliable way for TWA detection, and show the
      potential benefit of tensors in ECG signal processing.

PMID- 28745302
TI  - Advanced carbon nanotubes functionalization.
AB  - Similar to graphene, carbon nanotubes are materials made of pure carbon in its
      sp2 form. Their extended conjugated pi-network provides them with remarkable
      quantum optoelectronic properties. Frustratingly, it also brings drawbacks. The
      pi-pi stacking interaction makes as-produced tubes bundle together, blurring all
      their quantum properties. Functionalization aims at modifying and protecting the
      tubes while hindering pi-pi stacking. Several functionalization strategies have
      been developed to circumvent this limitation in order for nanotubes applications
      to thrive. In this review, we summarize the different approaches established so
      far, emphasizing the balance between functionalization efficacy and the
      preservation of the tubes' properties. Much attention will be given to a
      functionalization strategy overcoming the covalent-noncovalent dichotomy and to
      the implementation of two advanced functionalization schemes: (a) conjugation
      with molecular switches, to yield hybrid nanosystems with chemo-physical
      properties that can be tuned in a controlled and reversible way, and; (b)
      plasmonic nanosystems, whose ability to concentrate and enhance the
      electromagnetic fields can be taken advantage of to enhance the optical response
      of the tubes.

PMID- 28745303
TI  - Extracellular pH monitoring for use in closed-loop vagus nerve stimulation.
AB  - OBJECTIVE: Vagal nerve stimulation (VNS) has shown potential benefits for obesity
      treatment; however, current devices lack physiological feedback, which limit
      their efficacy. Changes in extracellular pH (pHe) have shown to be correlated
      with neural activity, but have traditionally been measured with glass
      microelectrodes, which limit their in vivo applicability. APPROACH: Iridium oxide
      has previously been shown to be sensitive to fluctuations in pH and is
      biocompatible. Iridium oxide microelectrodes were inserted into the
      subdiaphragmatic vagus nerve of anaesthetised rats. Introduction of the gut
      hormone cholecystokinin (CCK) or distension of the stomach was used to elicit
      vagal nerve activity. MAIN RESULTS: Iridium oxide microelectrodes have sufficient
      pH sensitivity to readily detect changes in pHe associated with both CCK and
      gastric distension. Furthermore, a custom-made Matlab script was able to use
      these changes in pHe to automatically trigger an implanted VNS device.
      SIGNIFICANCE: This is the first study to show pHe changes in peripheral nerves in
      vivo. In addition, the demonstration that iridium oxide microelectrodes are
      sufficiently pH sensitive as to measure changes in pHe associated with
      physiological stimuli means they have the potential to be integrated into closed
      loop neurostimulating devices.

PMID- 28745304
TI  - Multi-class chemical exposure in rural Peru using silicone wristbands.
AB  - Exposure monitoring with personal silicone wristband samplers was demonstrated in
      Peru in four agriculture and urban communities where logistic and practical
      constraints hinder use of more traditional approaches. Wristbands and associated
      methods enabled quantitation of 63 pesticides and screening for 1397 chemicals
      including environmental contaminants and personal care products. Sixty-eight
      wristbands were worn for approximately one month by volunteers from four
      communities of Alto Mayo, Peru. We identified 106 chemicals from eight chemical
      classes among all wristbands. Agricultural communities were characterized by
      pesticides and PAHs, while the urban communities had more personal care products
      present. Multiple linear regressions explained up to 40% of variance in
      wristbands from chlorpyrifos, cypermethrin, and DDT and its metabolites (DDx)
      (r2=0.39, 0.30, 0.40, respectively). All three pesticides were significantly
      different between communities, and cypermethrin and DDx were associated with
      participant age. The calculated relative age of DDT suggested some communities
      had more recent exposure than others. This work aids health research in the Alto
      Mayo and beyond by identifying typical mixtures and potential sources of exposure
      to organic chemicals in the personal environment. Silicone wristband sampling
      with chemical screening is a candidate for widespread use in exposure monitoring
      in remote areas.

PMID- 28745305
TI  - Preparation and performance features of wristband samplers and considerations for
      chemical exposure assessment.
AB  - Wristbands are increasingly used for assessing personal chemical exposures.
      Unlike some exposure assessment tools, guidelines for wristbands, such as
      preparation, applicable chemicals, and transport and storage logistics, are
      lacking. We tested the wristband's capacity to capture and retain 148 chemicals
      including polychlorinated biphenyls (PCBs), pesticides, flame retardants,
      polycyclic aromatic hydrocarbons (PAHs), and volatile organic chemicals (VOCs).
      The chemicals span a wide range of physical-chemical properties, with log octanol
      air partitioning coefficients from 2.1 to 13.7. All chemicals were quantitatively
      and precisely recovered from initial exposures, averaging 102% recovery with
      relative SD <=21%. In simulated transport conditions at +30  degrees C, SVOCs
      were stable up to 1 month (average: 104%) and VOC levels were unchanged (average:
      99%) for 7 days. During long-term storage at -20  degrees C up to 3 (VOCs) or 6
      months (SVOCs), all chemical levels were stable from chemical degradation or
      diffusional losses, averaging 110%. Applying a paired wristband/active sampler
      study with human participants, the first estimates of wristband-air partitioning
      coefficients for PAHs are presented to aid in environmental air concentration
      estimates. Extrapolation of these stability results to other chemicals within the
      same physical-chemical parameters is expected to yield similar results. As we
      better define wristband characteristics, wristbands can be better integrated in
      exposure science and epidemiological studies.

PMID- 28745307
TI  - A Longitudinal Study of Violent Behavior in a Psychosis-Risk Cohort.
AB  - There is a lack of insight into the relationships between violent ideation,
      violent behavior, and early, particularly attenuated, psychosis. Our aims were to
      examine the relationships between baseline violent behavior and violent ideation
      and outcome violent behavior and conversion to psychosis in at-risk individuals.
      We longitudinally assessed 200 individuals at clinical high risk for psychosis
      for violent ideation and violent behavior using the Structured Interview for
      Psychosis-Risk Syndromes (SIPS), and rated these according to MacArthur Community
      Violence categories. Fifty-six individuals (28%) reported violent ideation at
      baseline, 12 (6%) reported violent behavior within 6 months pre-baseline, and 8
      (4%) committed acts of violence during the follow-up time period. Information
      about violent ideation was obtained only by indirect, but not direct, inquiry
      about violent ideation. Both violent ideation and violent behavior at baseline
      significantly predicted violent behavior (RR=13.9, p=0.001; RR=8.3, p=0.003,
      respectively) during follow-up, as well as a diagnosis of psychosis (RR=2.3 and
      2.4, respectively; both p<0.001), independent of more than 40 clinical and
      demographic variables. The targets of the subjects' violent ideation at baseline
      were completely different than their subsequent targets of violent behavior.
      Violent behavior occurred within 7 days (SD 35 days) of a diagnosis of syndromal
      psychosis. These data suggest that checking carefully for violent ideation and
      behavior in clinical high-risk patients is essential, as these have predictive
      value for conversion to psychosis and likelihood of violence in the future.

PMID- 28745308
TI  - Coxsackievirus A16 utilizes cell surface heparan sulfate glycosaminoglycans as
      its attachment receptor.
AB  - Coxsackievirus A16 (CVA16) is one of the major pathogens responsible for hand,
      foot and mouth disease, which affects more than two million children in the Asian
      Pacific region annually. Previous studies have shown that scavenger receptor B2
      is a functional receptor for CVA16 that facilitates the uncoating process.
      However, it remains unclear whether other receptors are required for efficient
      CVA16 infection. In this study, by using a variety of assays we demonstrated that
      CVA16 utilizes surface heparan sulfate glycosaminoglycans as its attachment
      receptor. We further showed that five surface-exposed positively charged residues
      located in a cluster at the five-fold vertex of the virion are critical to
      heparan sulfate binding and cellular attachment of CVA16. Among the five
      residues, the arginine at position 166 (R166) of VP1 capsid protein appeared to
      be the most important for the interaction between CVA16 and heparan sulfate.
      Alanine substitution at this site (R166A) almost completely abolished heparan
      sulfate binding and cellular attachment of the virus. Our work achieves insight
      into the early events of CVA16 infection, thereby providing information that may
      facilitate the rational design of antiviral drugs and vaccines against CVA16
      infection.

PMID- 28745306
TI  - Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and
      Treatment of Posttraumatic Stress Disorder.
AB  - Exposure to stress is an undeniable, but in most cases surmountable, part of
      life. However, in certain individuals, exposure to severe or cumulative stressors
      can lead to an array of pathological conditions including posttraumatic stress
      disorder (PTSD), characterized by debilitating trauma-related intrusive thoughts,
      avoidance behaviors, hyperarousal, as well as depressed mood and anxiety. In the
      context of the rapidly changing political and legal landscape surrounding use of
      cannabis products in the USA, there has been a surge of public and research
      interest in the role of cannabinoids in the regulation of stress-related
      biological processes and in their potential therapeutic application for stress
      related psychopathology. Here we review the current state of knowledge regarding
      the effects of cannabis and cannabinoids in PTSD and the preclinical and clinical
      literature on the effects of cannabinoids and endogenous cannabinoid signaling
      systems in the regulation of biological processes related to the pathogenesis of
      PTSD. Potential therapeutic implications of the reviewed literature are also
      discussed. Finally, we propose that a state of endocannabinoid deficiency could
      represent a stress susceptibility endophenotype predisposing to the development
      of trauma-related psychopathology and provide biologically plausible support for
      the self-medication hypotheses used to explain high rates of cannabis use in
      patients with trauma-related disorders.

PMID- 28745309
TI  - A quantitative and efficient approach to select MIRU-VNTR loci based on
      accumulation of the percentage differences of strains for discriminating
      divergent Mycobacterium tuberculosis sublineages.
AB  - Although several optimal mycobacterial interspersed repetitive units-variable
      number tandem repeat (MIRU-VNTR) loci have been suggested for genotyping
      homogenous Mycobacterium tuberculosis, including the Beijing genotype, a more
      efficient and convenient selection strategy for identifying optimal VNTR loci is
      needed. Here 281 M. tuberculosis isolates were analyzed. Beijing genotype and non
      Beijing genotypes were identified, as well as Beijing sublineages, according to
      single nucleotide polymorphisms. A total of 22 MIRU-VNTR loci were used for
      genotyping. To efficiently select optimal MIRU-VNTR loci, we established
      accumulations of percentage differences (APDs) between the strains among the
      different genotypes. In addition, we constructed a minimum spanning tree for
      clustering analysis of the VNTR profiles. Our findings showed that eight MIRU
      VNTR loci displayed disparities in h values of >=0.2 between the Beijing genotype
      and non-Beijing genotype isolates. To efficiently discriminate Beijing and non
      Beijing genotypes, an optimal VNTR set was established by adding loci with APDs
      ranging from 87.2% to 58.8%, resulting in the construction of a nine-locus set.
      We also found that QUB11a is a powerful locus for separating ST10s (including
      ST10, STF and STCH1) and ST22s (including ST22 and ST8) strains, whereas a
      combination of QUB11a, QUB4156, QUB18, Mtub21 and QUB26 could efficiently
      discriminate Beijing sublineages. Our findings suggested that two nine-locus sets
      were not only efficient for distinguishing the Beijing genotype from non-Beijing
      genotype strains, but were also suitable for sublineage genotyping with different
      discriminatory powers. These results indicate that APD represents a quantitative
      and efficient approach for selecting MIRU-VNTR loci to discriminate between
      divergent M. tuberculosis sublineages.

PMID- 28745310
TI  - A two-step algorithm for rapid diagnosis of active pulmonary tuberculosis in
      entry applicants using the T-SPOT.TB and Xpert MTB/RIF assays in Shanghai, China.

PMID- 28745312
TI  - Splicing: Phasing alternative exons.

PMID- 28745313
TI  - Adult stem cells: Fat cells promote blood regeneration.

PMID- 28745311
TI  - Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and
      virulence in Francisella tularensis LVS.
AB  - Francisella tularensis is a highly infectious intracellular pathogen that infects
      a wide range of host species and causes fatal pneumonic tularemia in humans. ftlA
      was identified as a potential virulence determinant of the F. tularensis live
      vaccine strain (LVS) in our previous transposon screen, but its function remained
      undefined. Here, we show that an unmarked deletion mutant of ftlA was avirulent
      in a pneumonia mouse model with a severely impaired capacity to infect host
      cells. Consistent with its sequence homology with GDSL lipase/esterase family
      proteins, the FtlA protein displayed lipolytic activity in both E. coli and F.
      tularensis with a preference for relatively short carbon-chain substrates. FtlA
      thus represents the first F. tularensis lipase to promote bacterial infection of
      host cells and in vivo fitness. As a cytoplasmic protein, we found that FtlA was
      secreted into the extracellular environment as a component of outer membrane
      vesicles (OMVs). Further confocal microscopy analysis revealed that the FtlA
      containing OMVs isolated from F. tularensis LVS attached to the host cell
      membrane. Finally, the OMV-associated FtlA protein complemented the genetic
      deficiency of the DeltaftlA mutant in terms of host cell infection when OMVs
      purified from the parent strain were co-incubated with the mutant bacteria. These
      lines of evidence strongly suggest that the FtlA lipase promotes F. tularensis
      adhesion and internalization by modifying bacterial and/or host molecule(s) when
      it is secreted as a component of OMVs.

PMID- 28745314
TI  - A muscle-specific protein 'myoferlin' modulates IL-6/STAT3 signaling by
      chaperoning activated STAT3 to nucleus.
AB  - Myoferlin, a member of ferlin family of proteins, was first discovered as a
      candidate gene for muscular dystrophy and cardiomyopathy. Recently, myoferlin was
      shown to be also expressed in endothelial and cancer cells where it was shown to
      modulate vascular endothelial growth factor (VEGFR)-2 and epidermal growth factor
      receptor (EGFR) signaling by enhancing their stability and recycling. Based on
      these reports, we hypothesized that myoferlin might be regulating IL-6 signaling
      by modulating IL-6R stabilization and recycling. However, in our
      immunoprecipitation (IP) experiments, we did not observe myoferlin binding with
      IL-6R. Instead, we made a novel discovery that in resting cells myoferlin was
      bound to EHD2 protein and when cells were treated with IL-6, myoferlin
      dissociated from EHD2 and binds to activated STAT3. Interestingly, myoferlin
      depletion did not affect STAT3 phosphorylation, but completely blocked STAT3
      translocation to nucleus. In addition, inhibition of STAT3 phosphorylation by
      phosphorylation-defective STAT3 mutants or JAK inhibitor blocked STAT3 binding to
      myoferlin and nuclear translocation. Myoferlin knockdown significantly decreased
      IL-6-mediated tumor cell migration, tumorsphere formation and ALDH-positive
      cancer stem cell population, in vitro. Furthermore, myoferlin knockdown
      significantly decreased IL-6-meditated tumor growth and tumor metastasis. Based
      on these results, we have proposed a novel model for the role of myoferlin in
      chaperoning phosphorylated STAT3 to the nucleus.

PMID- 28745315
TI  - miR-302/367/LATS2/YAP pathway is essential for prostate tumor-propagating cells
      and promotes the development of castration resistance.
AB  - Clinical intervention for patients with advanced prostate cancer (PCa) remains
      challenging due to the inevitable recurrence of castration-resistant prostate
      cancer (CRPC) after androgen deprivation therapy (ADT). Cancer stem cells (CSCs)
      with serial tumor-propagating capacity are considered to be the driving force for
      PCa progression and recurrence. In this study, we report that the miR-302/367
      cluster, a previously identified potent pluripotency regulator, is upregulated in
      prostate tumors. Specifically, the forced expression of the miR-302/367 cluster
      accelerates the in vitro and in vivo growth of PCa cells and their resistance to
      androgen ablation, whereas the knockdown of the miR-302/367 cluster using anti
      sense RNA suppresses the incidence of formation, growth rate and endpoint weight
      of PCa cell tumors. Mechanistically, we find that LATS2, a key component of the
      tumor-suppressive Hippo signaling pathway, acts as a direct target of the miR
      302/367 cluster in PCa cells. The downregulation of LATS2 by the miR-302/367
      cluster reduces the phosphorylation and enhances the nuclear translocation of the
      YAP oncoprotein. Conversely, the restoration of LATS2 expression abrogates the
      tumor-promoting effects of forced miR-302/367 cluster expression. Collectively,
      the potent pluripotency regulator-triggered miR-302/367/LATS2/YAP pathway is
      essential for prostate tumor-propagating cells and promotes castration
      resistance. Thus, targeting this signaling axis may represent a promising
      therapeutic strategy for CRPC.

PMID- 28745316
TI  - Elevation of adenylate energy charge by angiopoietin-like 4 enhances epithelial
      mesenchymal transition by inducing 14-3-3gamma expression.
AB  - Metastatic cancer cells acquire energy-intensive processes including increased
      invasiveness and chemoresistance. However, how the energy demand is met and the
      molecular drivers that coordinate an increase in cellular metabolic activity to
      drive epithelial-mesenchymal transition (EMT), the first step of metastasis,
      remain unclear. Using different in vitro and in vivo EMT models with clinical
      patient's samples, we showed that EMT is an energy-demanding process fueled by
      glucose metabolism-derived adenosine triphosphate (ATP). We identified
      angiopoietin-like 4 (ANGPTL4) as a key player that coordinates an increase in
      cellular energy flux crucial for EMT via an ANGPTL4/14-3-3gamma signaling axis.
      This augmented cellular metabolic activity enhanced metastasis. ANGPTL4 knockdown
      suppresses an adenylate energy charge elevation, delaying EMT. Using an in vivo
      dual-inducible EMT model, we found that ANGPTL4 deficiency reduces cancer
      metastasis to the lung and liver. Unbiased kinase inhibitor screens and Ingenuity
      Pathway Analysis revealed that ANGPTL4 regulates the expression of 14-3-3gamma
      adaptor protein via the phosphatidylinositol-3-kinase/AKT and mitogen-activated
      protein kinase signaling pathways that culminate to activation of transcription
      factors, CREB, cFOS and STAT3. Using a different mode of action, as compared with
      protein kinases, the ANGPTL4/14-3-3gamma signaling axis consolidated cellular
      bioenergetics and stabilized critical EMT proteins to coordinate energy demand
      and enhanced EMT competency and metastasis, through interaction with specific
      phosphorylation signals on target proteins.

PMID- 28745317
TI  - Reticulocalbin-2 enhances hepatocellular carcinoma proliferation via modulating
      the EGFR-ERK pathway.
AB  - Hepatocellular carcinoma (HCC) is a major health threat worldwide. Although the
      involvement of reticulocalbin-2 (RCN2) in cell differentiation has been reported,
      its function in oncogenesis is poorly understood. Here, we showed that RCN2 was
      upregulated in tumors compared with adjacent non-tumorous tissues in HCC patients
      and RCN2 expression clinically correlated with tumor size, disease recurrence and
      survival rate. Both knockdown and knockout of RCN2 significantly inhibited HCC
      cell proliferation by inducing G1/S transition arrest and downregulating cyclin
      D1 expression, while the proliferative ability was restored in knockout HCC cells
      with exogenously expressed RCN2. Mechanistically, we demonstrated that RCN2
      interacted with the epidermal growth factor receptor (EGFR). Knockout of RCN2 in
      HCC cells not only inhibited activation of the EGFR-ERK pathway by blocking EGF
      mediated EGFR dimerization and internalization but also suppressed cell
      proliferation and EGFR phosphorylation under long exposure to EGF. We further
      showed that knockout of RCN2 inhibited EGFR phosphorylation, Ki-67 expression and
      tumor growth in nude mice. Moreover, we demonstrated that RCN2 knockout
      sensitized HCC cells to tyrosine kinase inhibitors, including erlotinib,
      lapatinib and sunitinib. Taken together, our results indicate that RCN2 plays a
      pivotal role in HCC cell proliferation and tumor growth presumably through
      regulating activation of the EGFR-ERK pathway. Our work also suggests that RCN2
      is a potential therapeutic target of HCC.

PMID- 28745318
TI  - Core 3 mucin-type O-glycan restoration in colorectal cancer cells promotes
      MUC1/p53/miR-200c-dependent epithelial identity.
AB  - The attachment of cell-surface carbohydrates to proteins mediated by the amino
      acids serine or threonine (O-glycan) is involved in tumor metastasis; the roles
      of O-glycans vary depending on their structure, but the detailed mechanisms by
      which O-glycans trigger signaling to control tumor metastasis are largely
      unknown. In this study, we found that the reduced expression of core 3 synthase
      correlated with metastasis to lymph nodes and distant organs, resulting in poor
      prognosis for colorectal cancer (CRC) patients. Mechanically, we revealed that
      mucin-type core 3 O-glycan was synthesized at the membrane-tethered MUC1 N
      terminus because of core 3 synthase expression in colon cancer cells. This
      further inhibited the translocation of MUC1-C to the nucleus, initiated p53 gene
      transcription that was dependent on the inhibition of MUC1-C nucleus
      translocation, activated p53-mediated miR-200c expression and resulted in
      mesenchymal-epithelial transition (MET). Inhibition of MUC1 via small interfering
      RNA (siRNA) in re-expressed core 3 synthase colon cancer cells further inhibited
      MUC1-C nucleus translocation, increased p53 and miR-200c expression, and enhanced
      MET. However, inhibition of p53 via siRNA or miR-200c via miR-200c inhibitor in
      re-expressed core 3 synthase colon cancer cells promoted the epithelial
      mesenchymal transition (EMT) in a reversible manner. Core 3 synthase mRNA levels
      and the p53 mRNA levels or miR-200c levels in the colon cancerous samples were
      positively correlated. Our findings suggest a novel mechanism linking mucin-type
      core 3 O-glycan to the EMT-MET plasticity of CRC cells via MUC1/p53/miR-200c
      dependent signaling cascade and shed light on therapeutic strategies to treat
      this malignancy.

PMID- 28745319
TI  - The androgen receptor is a negative regulator of eIF4E phosphorylation at S209:
      implications for the use of mTOR inhibitors in advanced prostate cancer.
AB  - The antiandrogen bicalutamide is widely used in the treatment of advanced
      prostate cancer (PCa) in many countries, but its effect on castration-resistant
      PCa (CRPC) is limited. We previously showed that resistance to bicalutamide
      results from activation of mechanistic target of rapamycin (mTOR). Interestingly,
      clinical trials testing combinations of the mTOR inhibitor RAD001 with
      bicalutamide were effective in bicalutamide-naive CRPC patients, but not in
      bicalutamide-pretreated ones. Here we investigate causes for their difference in
      response. Evaluation of CRPC cell lines identified resistant vs sensitive in
      vitro models, and revealed that increased eIF4E(S209) phosphorylation is
      associated with resistance to the combination. We confirmed using a human-derived
      tumor xenograft mouse model that bicalutamide pre-treatment is associated with an
      increase in eIF4E(S209) phosphorylation. Thus, AR suppressed eukaryotic
      initiation factor 4E (eIF4E) phosphorylation, while the use of antiandrogens
      relieved this suppression, thereby triggering its increase. Additional
      investigation in human prostatectomy samples showed that increased eIF4E
      phosphorylation strongly correlated with the cell proliferation marker Ki67.
      Small interfering RNA-mediated knockdown (k/d) of eIF4E-sensitized CRPC cells to
      RAD001+bicalutamide, whereas eIF4E overexpression induced resistance. Inhibition
      of eIF4E phosphorylation by treatment with CGP57380 (an inhibitor of mitogen
      activated protein kinase-interacting serine-threonine kinases MAP kinase
      interacting kinase 1 (Mnk1/2), the eIF4E upstream kinase) or inhibitors of
      extracellular signal-regulated kinase 1/2 (ERK1/2), the upstream kinase
      regulating Mnk1/2, also sensitized CRPC cells to RAD001+bicalutamide. Examination
      of downstream targets of eIF4E-mediated translation, including survivin,
      demonstrated that eIF4E(S209) phosphorylation increased cap-independent
      translation, whereas its inhibition restored cap-dependent translation, which
      could be inhibited by mTOR inhibitors. Thus, our results demonstrate that while
      combinations of AR and mTOR inhibitors were effective in suppressing tumor growth
      by inhibiting both AR-induced transcription and mTOR-induced cap-dependent
      translation, pre-treatment with AR antagonists including bicalutamide increased
      eIF4E phosphorylation that induced resistance to combinations of AR and mTOR
      inhibitors by inducing cap-independent translation. We conclude that this
      resistance can be overcome by inhibiting eIF4E phosphorylation with Mnk1/2 or
      ERK1/2 inhibitors.

PMID- 28745320
TI  - Surfactant protein D inhibits activation of non-small cell lung cancer-associated
      mutant EGFR and affects clinical outcomes of patients.
AB  - Tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant mutations of
      epidermal growth factor receptor (EGFR) are associated with lung adenocarcinoma.
      EGFR mutants were previously shown to exhibit ligand-independent activation. We
      have previously demonstrated that pulmonary surfactant protein D (SP-D, SFTPD)
      suppressed wild-type EGFR signaling by blocking ligand binding to EGFR. We herein
      demonstrate that SFTPD downregulates ligand-independent signaling in cells
      harboring EGFR mutations such as TKI-sensitive exon 19 deletion (Ex19del) and
      L858R mutation as well as TKI-resistant T790M mutation, subsequently suppressing
      cellular growth and motility. Lectin blotting and ligand blotting in lung cancer
      cell lines suggested that EGFR mutants express oligomannose-type N-glycans and
      interact with SFTPD directly. Cross-linking assay indicated that SFTPD inhibits
      ligand-independent dimerization of EGFR mutants. We also demonstrated that SFTPD
      reduced dimerization-independent phosphorylation of Ex19del and T790M EGFR
      mutants using point mutations that disrupted the asymmetric dimer interface. It
      was confirmed that SFTPD augmented the viability-suppressing effects of EGFR
      TKIs. Furthermore, retrospective analysis of 121 patients with lung
      adenocarcinoma to examine associations between serum SFTPD levels and clinical
      outcome indicated that in TKI-treated patients with lung cancer harboring EGFR
      mutations, including Ex19del or L858R, high serum SFTPD levels correlated with a
      lower number of distant metastases and prolonged overall survival and progression
      free survival. These findings suggest that SFTPD downregulates both TKI-sensitive
      and -resistant EGFR mutant signaling, and SFTPD level is correlated with clinical
      outcome. These findings illustrate the use of serum SFTPD level as a potential
      marker to estimate the efficacy of EGFR-TKIs.

PMID- 28745321
TI  - Conditional expression of Ki-RasG12V in the mammary epithelium of transgenic mice
      induces estrogen receptor alpha (ERalpha)-positive adenocarcinoma.
AB  - Appropriate 'in vivo' models are crucial for studying breast cancer biology and
      evaluating the efficacy of therapeutic agents. Thus we engineered a novel
      transgenic mouse line expressing the human Ki-Ras bearing an activating mutation
      (Ki-Ras(G12V)) selectively in the mammary epithelium after lactation. These mice
      develop invasive ductal adenocarcinomas with 100% incidence within 3-9 months
      after Ki-Ras(G12V) induction. Immunophenotyping revealed that the mammary tumors
      express luminal markers, are positive for estrogen and progesterone receptors,
      negative for HER2 and have a low proliferation index. Moreover, cell lines
      derived from such tumors are estrogen-responsive and, when transplanted into nude
      mice, form tumors that respond to the antiestrogen ICI 182780. In conclusion, the
      mammary tumors of these transgenic mice and the derived cell lines exhibit key
      features of the major form of human breast cancer, that is, luminal A subtype and
      thus have a high potential for breast cancer research and treatment.

PMID- 28745323
TI  - Dysphagia Due to Kindler Syndrome.

PMID- 28745322
TI  - p53 loss does not permit escape from BrafV600E-induced senescence in a mouse
      model of lung cancer.
AB  - Lung cancer arises through the acquisition of a number of genetic lesions, with a
      preponderance of activating mutations in the canonical mitogen-activated protein
      kinase (MAPK) cascade (RTK-RAS-RAF-MEK). BrafV600E expression induces benign lung
      adenomas that fail to progress to adenocarcinoma because of oncogene-induced
      senescence (OIS). BrafV600E expression, coupled with simultaneous p53 ablation,
      permits bypass of senescence and progression to lung adenocarcinoma. However,
      spontaneous human tumors sustain mutations in a temporally separated manner.
      Here, we use a mouse lung cancer model where oncogene activation (BrafV600E
      expression) and tumor suppressor loss (p53 ablation) are independently controlled
      through the actions of Flp and Cre recombinase, respectively. We show that p53
      loss before OIS is permissive for the transition from lung adenoma to
      adenocarcinoma. In contrast, p53 loss after senescence is established fails to
      enable escape from senescence and disease progression. This study demonstrates
      that BrafV600E induced senescence is irreversible in vivo and suggests that
      therapy-induced senescence would halt further tumor progression.

PMID- 28745324
TI  - A committed postselection precursor to natural TCRalphabeta+ intraepithelial
      lymphocytes.
AB  - The intestine is a major immune organ with several specialized lymphoid
      structures and immune cells. Among these are thymus-derived natural
      intraepithelial lymphocytes (IELs) that lack expression of the classical co
      receptors CD4 or CD8alphabeta (double negative (DN)). Natural IELs are both
      alphabeta+ and gammadelta+ T cells that play important roles in the maintenance
      of the epithelial barrier at steady state and during inflammation. The
      transcription factor T-bet is essential for the peripheral development of natural
      IELs, but its role during thymic development has remained less clear. Here we
      show that a T-bet gradient in DN TCRalphabeta+NK1.1- thymocytes (IEL precursors
      (IELPs)) determines IEL fate in natural TCRalphabeta+ IELs. Employing T-bet
      ZsGreen reporter mice in in vitro cultures and in vivo transfer experiments, we
      demonstrate that with increasing expression of T-bet, DN TCRalphabeta+NK1.1-
      thymocytes are gradually restricted to a DN IEL fate. Furthermore, we show that
      the natural TCRalphabeta+ IELs seed the intestine within the first month of life.
      This in turn is preceded by the appearance of T-bet- and T-bet+ IELPs that egress
      from the thymus in a sphingosine-1-phosphate (S1P)-dependent manner. In summary,
      the use of T-bet reporter mice has enabled us to identify and refine an immediate
      and clearly committed postselection precursor of natural TCRalphabeta+ IELs.

PMID- 28745326
TI  - Defective positioning in granulomas but not lung-homing limits CD4 T-cell
      interactions with Mycobacterium tuberculosis-infected macrophages in rhesus
      macaques.
AB  - Protection against Mycobacterium tuberculosis (Mtb) infection requires CD4 T
      cells to migrate into the lung and interact with infected macrophages. In mice,
      less-differentiated CXCR3+ CD4 T cells migrate into the lung and suppress growth
      of Mtb, whereas CX3CR1+ terminally differentiated Th1 cells accumulate in the
      blood vasculature and do not control pulmonary infection. Here we examine CD4 T
      cell differentiation and lung homing during primary Mtb infection of rhesus
      macaques. Mtb-specific CD4 T cells simultaneously appeared in the airways and
      blood ~21-28 days post exposure, indicating that recently primed effectors are
      quickly recruited into the lungs after entering circulation. Mtb-specific CD4 T
      cells in granulomas display a tissue-parenchymal CXCR3+CX3CR1-PD-1hiCTLA-4+
      phenotype. However, most granuloma CD4 T cells are found within the outer
      lymphocyte cuff and few localize to the myeloid cell core containing the bacilli.
      Using the intravascular stain approach, we find essentially all Mtb-specific CD4
      T cells in granulomas have extravasated across the vascular endothelium into the
      parenchyma. Therefore, it is unlikely to be that lung-homing defects introduced
      by terminal differentiation limit the migration of CD4 T cells into granulomas
      following primary Mtb infection of macaques. However, intralesional positioning
      defects within the granuloma may pose a major barrier to T-cell-mediated immunity
      during tuberculosis.

PMID- 28745325
TI  - The regulation of gut mucosal IgA B-cell responses: recent developments.
AB  - The majority of activated B cells differentiate into IgA plasma cells, with the
      gut being the largest producer of immunoglobulin in the body. Secretory IgA
      antibodies have numerous critical functions of which protection against
      infections and the role for establishing a healthy microbiota appear most
      important. Expanding our knowledge of the regulation of IgA B-cell responses and
      how effective mucosal vaccines can be designed are of critical importance. Here
      we discuss recent developments in the field that shed light on the uniqueness and
      complexity of mucosal IgA responses and the control of protective IgA responses
      in the gut, specifically.

PMID- 28745327
TI  - Seminal vesicle fluid increases the efficacy of intravaginal HSV-2 vaccination.
AB  - Once considered merely as a vehicle for spermatozoa, it is now clear that seminal
      plasma (SP) induces a variety of biological actions on the female reproductive
      tissues able to modulate the immune response against paternal antigens. To our
      knowledge, the influence of SP on the immune response against sexually
      transmitted pathogens has not been yet evaluated. We here analyzed whether the
      seminal vesicle fluid (SVF), which contributes almost 60% of the SP volume in
      mice, could modulate the immune response against herpes simplex virus type 2 (HSV
      2). We found that SVF does not modify the course of primary infection, but
      markedly improved protection conferred by vaginal vaccination with inactivated
      HSV-2 against a lethal challenge. This protective effect was shown to be
      associated to a robust memory immune response mediated by CD4+ and CD8+ T cells
      in both the lymph nodes draining the vagina and the vaginal mucosa, the site of
      viral replication. In contrast with the widespread notion that SP acts as an
      immunosuppressive agent, our results suggest that SVF might improve the female
      immune response against sexually transmitted pathogens.

PMID- 28745328
TI  - Diacylglycerol kinase synthesized by commensal Lactobacillus reuteri diminishes
      protein kinase C phosphorylation and histamine-mediated signaling in the
      mammalian intestinal epithelium.
AB  - Lactobacillus reuteri 6475 (Lr) of the human microbiome synthesizes histamine and
      can suppress inflammation via type 2 histamine receptor (H2R) activation in the
      mammalian intestine. Gut microbes such as Lr promote H2R signaling and may
      suppress H1R proinflammatory signaling pathways in parallel by unknown
      mechanisms. In this study, we identified a soluble bacterial enzyme known as
      diacylglycerol kinase (Dgk) from Lr that is secreted into the extracellular
      milieu and presumably into the intestinal lumen. DgK diminishes diacylglycerol
      (DAG) quantities in mammalian cells by promoting its metabolic conversion and
      causing reduced protein kinase C phosphorylation (pPKC) as a net effect in
      mammalian cells. We demonstrated that histamine synthesized by gut microbes (Lr)
      activates both mammalian H1R and H2R, but Lr-derived Dgk suppresses the H1R
      signaling pathway. Phospho-PKC and IkappaBalpha were diminished within the
      intestinal epithelium of mice and humans treated by wild-type (WT) Lr, but pPKC
      and IkappaBalpha were not decreased in treatment with DeltadgkA Lr. Mucosal IL-6
      and systemic interleukin (IL)-1alpha, eotaxin, and granulocyte colony-stimulating
      factor (G-CSF) were suppressed in WT Lr, but not in DeltadgkA Lr colonized mice.
      Collectively, the commensal microbe Lr may act as a "microbial antihistamine" by
      suppressing intestinal H1R-mediated proinflammatory responses via diminished pPKC
      mediated mammalian cell signaling.

PMID- 28745329
TI  - Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF
      patients.
AB  - Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by
      hyperplastic megakaryopoiesis and myelofibrosis. We recently described the
      upregulation of MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene
      homolog) in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to healthy
      donor. Here we demonstrated that MAF is also upregulated in PMF compared with the
      essential thrombocytemia (ET) and polycytemia vera (PV) HPCs. MAF overexpression
      and knockdown experiments shed some light into the role of MAF in PMF
      pathogenesis, by demonstrating that MAF favors the megakaryocyte and
      monocyte/macrophage commitment of HPCs and leads to the increased expression of
      proinflammatory and profibrotic mediators. Among them, we focused our further
      studies on SPP1 and LGALS3. We assessed SPP1 and LGALS3 protein levels in 115
      PMF, 47 ET and 24 PV patients plasma samples and we found that SPP1 plasma levels
      are significantly higher in PMF compared with ET and PV patients. Furthermore, in
      vitro assays demonstrated that SPP1 promotes fibroblasts and mesenchymal stromal
      cells proliferation and collagen production. Strikingly, clinical correlation
      analyses uncovered that higher SPP1 plasma levels in PMF patients correlate with
      a more severe fibrosis degree and a shorter overall survival. Collectively our
      data unveil that MAF overexpression contributes to PMF pathogenesis by driving
      the deranged production of the profibrotic mediator SPP1.

PMID- 28745331
TI  - CD47 blockade enhances therapeutic activity of TCR mimic antibodies to ultra-low
      density cancer epitopes.

PMID- 28745330
TI  - Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a
      distinct clinical and biological entity in the era of immunotherapy.
AB  - In diffuse large B-cell lymphoma (DLBCL), the clinical and biological
      significance of concordant and discordant bone marrow (BM) involvement have not
      been well investigated. We evaluated 712 de novo DLBCL patients with front-line
      rituximab-containing treatment, including 263 patients with positive and 449 with
      negative BM status. Compared with negative BM disease, concordant BM adversely
      impacted overall and progression-free survival, independent of the International
      Prognostic Index (IPI) and cell-of-origin classification. Once BM is concordantly
      involved, poor prognosis was not associated with the extent of BM involvement.
      Conversely, patients with discordant BM showed favorable overall survival similar
      to stage I-II DLBCL. A BM-adjusted IPI, using three parameters: concordant BM
      involvement, age >60 years, and performance status >1, improves the risk
      stratification for DLBCL with positive BM. Intensive immunochemotherapy seemingly
      rendered survival benefit for patients with concordant BM, as did rituximab
      maintenance for the discordant BM group. Frequently revealing adverse clinical
      and molecular characteristics, patients with concordant BM demonstrated gene
      expression signatures relevant to tumor cell proliferation, migration and immune
      escape. In conclusion, clinical and biological heterogeneity is seen in DLBCL
      with positive BM but concordant BM involvement represents a distinct subset with
      unfavorable gene signatures, high-risk clinicopathologic features and poor
      prognosis.

PMID- 28745332
TI  - Impact of gender on outcome after chemoimmunotherapy in patients with chronic
      lymphocytic leukemia: a meta-analysis by the German CLL study group.

PMID- 28745333
TI  - Breakfast quality and cardiometabolic risk profiles in an upper middle-aged
      German population.
AB  - BACKGROUND/OBJECTIVES: Little is known about relation of overall breakfast
      quality with cardiometabolic risk factors. Therefore, this study aimed to explore
      sex-specific associations between breakfast quality and cardiometabolic risk
      profiles in a sample of an upper middle-aged German population. SUBJECTS/METHODS:
      Cardiometabolic profiles of 339 men and 329 women were cross-sectionally assessed
      using an overall biomarker score (BScore), glycated hemoglobin (HbA1c), high
      density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL
      C), triglycerides (TG), blood pressure, body mass index (BMI) and waist
      circumference (WC). Overall breakfast quality was assessed by using (i) an a
      priori defined breakfast quality score (BQS) and (ii) data-driven breakfast
      patterns based on principal component analysis (PCA). Multiple linear regression
      models for association of breakfast quality with all outcomes were adjusted for
      all potential confounders including overall diet quality. RESULTS: After
      adjustment for all potential confounders the BQS was inversely associated with
      the BScore (regression beta with 95% Confidence Interval: -0.29 (052-0.06)) and
      HbA1c (-0.12 (-0.21, -0.04)) in men; whereas no such associations were observed
      in women. Four breakfast (B) patterns were identified: B-processed-food pattern,
      B-cereal pattern, B-high fat pattern and B-dairy & cereal pattern. The B
      processed-food pattern was positively associated with HbA1c (0.09(0.01, 0.18)),
      BMI (0.16 (0.06, 0.26)), and WC (0.17 (0.8, 0.26)) in men, and BMI (0.13 (0.1,
      0.25)) and WC (0.11(0.01.0.22)) in women. The B-cereal pattern was inversely
      associated with BScore (-0.23 (-0.45, -0.01)) and BMI (-0.11 (-0.20, -0.01)) in
      men and WC(-0.16 (-0.27, -0.05)) in women. The B-dairy & cereal pattern was also
      inversely associated with BScore (-0.26 (-0.48, -0.04)) in men but not in women.
      CONCLUSIONS: The overall breakfast quality was cross-sectionally associated with
      a healthier cardiometabolic profile, especially in upper-middle age men,
      independent of overall dietary quality. Such analyses should be supplemented by
      studies investigating the circadian sequence of food intake and metabolic
      consequences including hard disease endpoints.

PMID- 28745334
TI  - Evaluation of the wrist-worn ActiGraph wGT3x-BT for estimating activity energy
      expenditure in preschool children.
AB  - BACKGROUND/OBJECTIVES: Easy-to-use and accurate methods to assess free-living
      activity energy expenditure (AEE) in preschool children are required. The aims of
      this study in healthy preschool children were to (a) evaluate the ability of the
      wrist-worn ActiGraph wGT3x-BT to predict free-living AEE and (b) assess wear
      compliance using a 7-day, 24-h protocol. SUBJECTS/METHODS: Participants were 40
      Swedish children (5.5+/-0.2 years) in the Mobile-based intervention intended to
      stop obesity in preschoolers (MINISTOP) obesity prevention trial. Total energy
      expenditure (TEE) was assessed using the doubly labeled water method during 14
      days. AEE was calculated as (TEEx0.9) minus predicted basal metabolic rate. The
      ActiGraph accelerometer was worn on the wrist for 7 days and outputs used were
      mean of the daily and awake filtered vector magnitude (mean VM total and mean VM
      waking). RESULTS: The ActiGraph was worn for 7 (n=34, 85%), 6 (n=4, 10%), 5 (n=1,
      2.5%) and 4 (n=1, 2.5%) days (a valid day was ?600 awake minutes). Alone, mean VM
      total and mean VM waking were able to explain 14% (P=0.009) and 24% (P=0.001) of
      the variation in AEE, respectively. By incorporating fat and fat-free mass in the
      models 58% (mean VM total) and 62% (mean VM waking) in the variation of AEE was
      explained (P<0.001). CONCLUSIONS: The wrist-worn ActiGraph wGT3x-BT in
      combination with body composition variables explained up to the 62% of the
      variation in AEE. Given the high wear compliance, the wrist-worn ActiGraph has
      the potential to provide useful information in studies where physical activity in
      preschool children is measured.

PMID- 28745335
TI  - To vegan or not to vegan when pregnant, lactating or feeding young children.

PMID- 28745336
TI  - Human embryonic stem cells and good manufacturing practice: Report of a 1- day
      workshop held at Stem Cell Biology Research Center, Yazd, 27th April 2017.
AB  - This report explains briefly the minutes of a 1-day workshop entitled; "human
      embryonic stem cells (hESCs) and good manufacturing practice (GMP)" held by Stem
      Cell Biology Research Center based in Yazd Reproductive Sciences Institute at
      Shahid Sadoughi University of Medical Sciences, Yazd, Iran on 27th April 2017. In
      this workshop, in addition to the practical sessions, Prof. Harry D. Moore from
      Centre for Stem Cell Biology, University of Sheffield, UK presented the
      challenges and the importance of the biotechnology of clinical-grade human
      embryonic stem cells from first derivation to robust defined culture for
      therapeutic applications.

PMID- 28745337
TI  - Understanding the metabolism of the anticancer drug Triapine: electrochemical
      oxidation, microsomal incubation and in vivo analysis using LC-HRMS.
AB  - alpha-N-Heterocyclic thiosemicarbazones are among the most promising
      ribonucleotide reductase inhibitors identified so far. Triapine, the most
      prominent representative of this class of substances, has been investigated in
      multiple phase I and II clinical trials. With regard to clinical practice,
      Triapine showed activity against hematological diseases, but ineffectiveness
      against a variety of solid tumors. However, the reasons are still vague and the
      amount of ADME (absorption, distribution, metabolism and excretion) data for
      Triapine available in the literature is very limited. Therefore, different
      analytical tools were used to investigate the metabolism of Triapine including
      electrochemical oxidations, liver microsomes and in vivo samples from mice. The
      main metabolic reactions, observed by all three methods, were dehydrogenation and
      hydroxylations, confirming that electrochemistry, as a purely instrumental
      approach, can be applied for the simulation of metabolic pathways. The
      dehydrogenated metabolite M1 was identified as a thiadiazole ring-closed
      oxidation product of Triapine. From a biological point of view, M1, as a key
      metabolite, is of interest since the crucial chemical property of alpha-N
      heterocyclic thiosemicarbazones to bind metal ions is lost and cytotoxicity
      studies showed no anticancer activity of M1. The in vivo data of the urine
      samples revealed very high levels of the metabolites and Triapine itself already
      15 min after treatment. This clearly indicates that Triapine is rapidly
      metabolised and excreted, which represents an important step forward to
      understand the possible reason for the inefficiency of Triapine against solid
      tumors.

PMID- 28745339
TI  - Sensitization of NIR luminescence of Yb3+ by Zn2+ chromophores in heterometallic
      complexes with a bridging Schiff-base ligand.
AB  - Herein, complexes [ZnL]2 (1), {(H2O)Zn(MU-L)Yb[OCH(CF3)2]3} (2),
      {[(CF3)2HCO]Zn(MU-L)Yb[OCH(CF3)2](MU-OH)}2 (3), and [(H2O)Ln2(L)3] (Ln = Yb (4)
      and Gd (5)) containing a bridging Schiff-base ligand (H2L = N,N'-bis(3-methoxy
      salicylidene)phenylene-1,2-diamine) were synthesized. The compounds 1-4 were
      structurally characterized. The ytterbium derivatives 2-4 exhibited bright NIR
      metal-centred photoluminescence (PL) of Yb3+ ion under one- (lambdaex = 380 nm)
      and two-photon (lambdaex = 750 nm) excitation. The superior luminescence
      properties of complex 2, which was suggested as a marker for NIR bioimaging, were
      explained via the strong absorption of the 375 nm LMCT state of the ZnL
      chromophore, efficient energy transfer from ZnL towards Yb3+ through a reversible
      ligand-to-lanthanide electron transfer process, and absence of luminescence
      quenchers (C-H and O-H groups) in the first coordination sphere of the rare-earth
      atom.

PMID- 28745340
TI  - Toward a quantitative description of microscopic pathway heterogeneity in protein
      folding.
AB  - How many structurally different microscopic routes are accessible to a protein
      molecule while folding? This has been a challenging question to address
      experimentally as single-molecule studies are constrained by the limited number
      of observed folding events while ensemble measurements, by definition, report
      only an average and not the distribution of the quantity under study. Atomistic
      simulations, on the other hand, are restricted by sampling and the inability to
      reproduce thermodynamic observables directly. We overcome these bottlenecks in
      the current work and provide a quantitative description of folding pathway
      heterogeneity by developing a comprehensive, scalable and yet experimentally
      consistent approach combining concepts from statistical mechanics, physical
      kinetics and graph theory. We quantify the folding pathway heterogeneity of five
      single-domain proteins under two thermodynamic conditions from an analysis of 100
      000 folding events generated from a statistical mechanical model incorporating
      the detailed energetics from more than a million conformational states. The
      resulting microstate energetics predicts the results of protein engineering
      experiments, the thermodynamic stabilities of secondary-structure segments from
      NMR studies, and the end-to-end distance estimates from single-molecule force
      spectroscopy measurements. We find that a minimum of ~3-200 microscopic routes,
      with a diverse ensemble of transition-path structures, are required to account
      for the total folding flux across the five proteins and the thermodynamic
      conditions. The partitioning of flux amongst the numerous pathways is shown to be
      subtly dependent on the experimental conditions that modulate protein stability,
      topological complexity and the structural resolution at which the folding events
      are observed. Our predictive methodology thus reveals the presence of rich
      ensembles of folding mechanisms that are generally invisible in experiments,
      reconciles the contradictory observations from experiments and simulations and
      provides an experimentally consistent avenue to quantify folding heterogeneity.

PMID- 28745341
TI  - Size dependent behavior of Fe3O4 crystals during electrochemical (de)lithiation:
      an in situ X-ray diffraction, ex situ X-ray absorption spectroscopy, transmission
      electron microscopy and theoretical investigation.
AB  - The iron oxide magnetite, Fe3O4, is a promising conversion type lithium ion
      battery anode material due to its high natural abundance, low cost and high
      theoretical capacity. While the close packing of ions in the inverse spinel
      structure of Fe3O4 enables high energy density, it also limits the kinetics of
      lithium ion diffusion in the material. Nanosizing of Fe3O4 to reduce the
      diffusion path length is an effective strategy for overcoming this issue and
      results in improved rate capability. However, the impact of nanosizing on the
      multiple structural transformations that occur during the electrochemical
      (de)lithiation reaction in Fe3O4 is poorly understood. In this study, the
      influence of crystallite size on the lithiation-conversion mechanisms in Fe3O4 is
      investigated using complementary X-ray techniques along with transmission
      electron microscopy (TEM) and continuum level simulations on electrodes of two
      different Fe3O4 crystallite sizes. In situ X-ray diffraction (XRD) measurements
      were utilized to track the changes to the crystalline phases during
      (de)lithiation. X-ray absorption spectroscopy (XAS) measurements at multiple
      points during the (de)lithiation processes provided local electronic and atomic
      structural information. Tracking the crystalline and nanocrystalline phases
      during the first (de)lithiation provides experimental evidence that (1) the
      lithiation mechanism is non-uniform and dependent on crystallite size, where
      increased Li+ diffusion length in larger crystals results in conversion to Fe0
      metal while insertion of Li+ into spinel-Fe3O4 is still occurring, and (2) the
      disorder and size of the Fe metal domains formed when either material is fully
      lithiated impacts the homogeneity of the FeO phase formed during the subsequent
      delithiation.

PMID- 28745342
TI  - Defense contracts: molecular protection in insect-microbe symbioses.
AB  - Insects cope with environmental threats using a broad array of strategies. A key
      strategy, widespread among insects but unappreciated until recently, is the use
      of molecular defenses from symbiotic microbes. Insect-microbe defensive symbioses
      span the diversity of insect lineages and microbial partners and use molecules
      ranging from reactive oxygen species to small molecules to protein toxins to
      defend against predators, parasites, and microbial pathogens. These systems have
      a strong initial track record as sources of novel biologically active compounds
      with therapeutic potential. This review surveys the molecular basis for insect
      microbe defensive symbioses with a focus on the ecological contexts for defense
      and on emerging lessons about molecular diversity from bacterial genomes.

PMID- 28745343
TI  - A comparative study of the influence of N,N'-dialkyl vs. N,N'-diaryl-based
      electron donor ancillary ligands on photocurrent and photovoltage in dye
      sensitized solar cells (DSSCs).
AB  - In this study, we report the synthesis of a novel heteroleptic Ru(ii)-sensitizer,
      (Ru(2,2'-bipyridine-4,4'-dicarboxylic acid)-4,4'-bis(4-piperidin-1-yl)phenyl
      ethenyl)-(2,2'-bipyridine) (NCS)2, denoted as SD-1; moreover, its photophysical,
      electrochemical, and photovoltaic performances were compared with those of N719
      and K77-7 (N,N'-diaryl Ru-sensitizer, namely Ru(2,2'-bipyridine-4,4'-dicarboxylic
      acid)-4,4'-bis(2-(4-N,N'-diphenylaminophenyl)ethenyl)-2,2'-bipyridine (NCS)2).
      The photovoltaic performance of SD-1 outperformed those of N-719 and K77-7,
      particularly in the red region, and the overall efficiency of SD-1 was 8.5% as
      compared to 8.0% of K77-7 and 7.7% of N719 under the same experimental device
      conditions. The superior light harvesting efficiency of SD-1 can be attributed to
      the strong electron donor sp3-nitrogen, which is attached to two sp3-carbons
      (dialkyl), whereas in the case of K77-7, all carbon atoms attached to the sp3
      nitrogen are sp2, which decrease the electron density on the latter and minimize
      the electron-donating power of the ancillary ligand in K77-7. To gain a
      quantitative understanding of the electron density on nitrogen in SD-1 and K77-7,
      first-principle calculations using molecular and thermodynamic descriptors, such
      as frontier molecular orbitals, ground-state oxidation potential (GSOP), excited
      state oxidation potential (ESOP), optical gap (E0-0), and charge distributions,
      were conducted in solution. In addition, for understanding the anchored
      structures of dyes on Ti24O48, density functional theory (DFT) and time-dependent
      density functional theory (TD-DFT) were utilized. Results of computational
      studies are in excellent agreement with the experimental results, which can be
      used as a screening tool for the design of more efficient molecular motifs for
      DSSCs.

PMID- 28745344
TI  - Fixation of atmospheric CO2 as novel carbonate-(water)2-carbonate cluster and
      entrapment of double sulfate within a linear tetrameric barrel of a neutral bis
      urea scaffold.
AB  - A meta-phenylenediamine-based disubstituted bis-urea receptor L1 with electron
      withdrawing 3-chloro and electron-donating 4-methylphenyl terminals has been
      established as a potential system to fix and efficiently capture atmospheric CO2
      as air-stable entrapment of an unprecedented {CO32--(H2O)2-CO32-} cluster
      (complex 1a) within its tetrameric long straight pillar-like assembly entirely
      sealed by n-TBA cations via formation of a barrel-type architecture. L1 and its
      isomeric 4-bromo-3-methyl disubstituted bis-urea receptor L2 have been found to
      entrap similar kinds of water-free naked sulfate-sulfate double anion (complexes
      1b and 2a) by cooperative binding of urea moieties inside the two pairs of the
      inversion-symmetric linear tetrameric barrel of L1 and L2, respectively. On the
      other hand, in the presence of excess halides, L1 self-assembles to form hexa
      coordinated fluoride complex 1c and tetra-coordinated bromide complex 1d, while
      L2 self-assembles to form penta-coordinated fluoride complex 2b in the solid
      state via semicircular receptor architectures and non-cooperative H-bonding
      interactions of urea moieties.

PMID- 28745345
TI  - High enrichment and ultra-trace analysis of aflatoxins in edible oils by a
      modified hollow-fiber liquid-phase microextraction technique.
AB  - An improved approach for the ultra-trace analysis of aflatoxins B1, B2, G1 and G2
      in edible oils was developed for the first time by a hollow-fiber liquid-phase
      microextraction (HF-LPME) technique. Good linearity, low limits of detection,
      high enrichment factors and good repeatability were obtained, which ensured the
      application of the method for ultra-trace detection of AFTs in edible oils.

PMID- 28745349
TI  - Photo-induced proton-coupled electron transfer and dissociation of isolated
      flavin adenine dinucleotide mono-anions.
AB  - The intrinsic optical absorption spectrum and photo-dissociation pathways of
      flavin adenine dinucleotide (FAD) mono-anions isolated in vacuo are probed using
      photo-induced dissociation (PID) action spectroscopy. The main photo-products are
      lumichrome and formylmethylflavin. Evidence is presented that the dissociation
      pathway leading to these products is non-statistical i.e. occurs during the
      excited state lifetime. This suggests that the stacking of the adenine and
      alloxazine chromophores, which enables ultra-fast quenching of the flavin excited
      state by photo-induced electron transfer in aqueous solution, is inhibited in
      vacuo. These results provide firm experimental confirmation that lumichrome
      formation from flavins proceeds via photo-induced, intra-molecular proton-coupled
      electron transfer.

PMID- 28745350
TI  - Tailoring the magnetic properties of FexCo(1-x) nanopowders prepared by a polyol
      process.
AB  - Precise control over the magnetic properties of FeCo alloys is of scientific
      significance, due to their high Curie points and saturation magnetizations, and
      of broad interest for applications such as transformer cores, induction motors,
      switching devices, and hyperthermia. The magnetic properties of FexCo(1-x) alloy
      based nanopowders prepared by polyol synthesis and their relationship with
      morphological features and the evolution of the microstructure were investigated
      using a design of experiments (DoE) approach. Proportionalities related to the
      magnetic properties, saturation magnetization (Ms) and coercivity (Hc), were
      identified where Ms ? (110) crystallite size of FeCo (bcc) and Hc ? particle
      diameter for the as-synthesized FexCo(1-x) nanopowders. Adjusting the reaction
      composition allows for control of the FeCo (bcc) (110) crystallite size from 20
      45 nm represented by a response surface model. Morphological features of the as
      synthesized nanopowders include particles interlinked as chains, and particles
      either in the form of cuboids or spheroids, all with diameters ranging from 75
      175 nm. FexCo(1-x) alloy was confirmed by XRD in each nanopowder while few
      contained a combination of phases which include Co (fcc), or ferrite (CoFe2O4),
      or both. Depending on composition, particle dimension, and microstructure, the Ms
      ranged from 90-215 emu g-1 with Hc from 90-400 Oe for all nanopowders synthesized
      by the sub-reflux, isothermal condition (150  degrees C). Tailoring the magnetic
      properties of FexCo(1-x) alloy-based nanopowders is accomplished chemically by
      identifying and regulating significant reaction parameters and conditions.

PMID- 28745351
TI  - Atmospheric concentrations and gas-particle partitioning of polycyclic aromatic
      hydrocarbons (PAHs) and nitro-PAHs at Indo-Gangetic sites.
AB  - Aerosol samples in the dual-phase (gaseous and particulate) were collected
      simultaneously for the first time in Agra at a rural and a traffic dominated site
      during post-monsoon and winter seasons to investigate the gas-particle
      partitioning of polycyclic aromatic hydrocarbons (PAHs). The samples were
      collected using a high volume sampler on quartz micro-fiber filter papers and
      polyurethane foam plugs for particulate and gas phases respectively. The samples
      were extracted in a mixture of DCM and n-hexane. 16 priority PAHs and two nitro
      PAHs were analyzed using gas chromatograph-mass spectrometry. The total
      concentration of PAHs (gas + particulate) was 4015 and 624 ng m-3 at the traffic
      and rural sites respectively. Two and three ring PAHs were dominant in the gas
      phase while four, five and six ring PAHs were abundant in the particle phase. A
      statistically significant correlation (r2 = 0.69-0.98, p < 0.001) for log Kpvs.
      was obtained for individual PAHs at both sites where slopes varied between -2.83
      and -0.04 at the traffic site and from -3.15 to -0.06 at the rural site.
      Regression statistics of Clausius-Clapeyron plots suggest that the concentration
      of highly volatile PAHs in the atmosphere is influenced by temperature. The gas
      particle partitioning coefficient Kp in its logarithmic form correlated with 1/T
      (r2 = 0.5-0.95, p < 0.001) and a positive slope for individual PAHs was found. In
      health risk assessment DbA was found to be the most carcinogenic and mutagenic as
      compared to other PAHs followed by BaP. 1-NPyr had a larger contribution to BaP
      TEQ than 3-NFla.

PMID- 28745352
TI  - Airborne persistent toxic substances (PTSs) in China: occurrence and its
      implication associated with air pollution.
AB  - In recent years, China suffered from extensive air pollution due to the rapidly
      expanding economic and industrial developments. Its severe impact on human health
      has raised great concern currently. Persistent toxic substances (PTSs), a large
      group of environmental pollutants, have also received much attention due to their
      adverse effects on both the ecosystem and public health. However, limited studies
      have been conducted to reveal the airborne PTSs associated with air pollution at
      the national scale in China. In this review, we summarized the occurrence and
      variation of airborne PTSs in China, especially in megacities. These PTSs
      included polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs),
      polychlorinated biphenyls (PCBs), halogenated flame retardants (HFRs),
      perfluorinated compounds (PFCs), organochlorine pesticides (OCPs), polycyclic
      aromatic hydrocarbons (PAHs) and heavy metals. The implication of their
      occurrence associated with air pollution was discussed, and the emission source
      of these chemicals was concluded. Most reviewed studies have been conducted in
      east and south China with more developed economy and industry. Severe
      contamination of airborne PTSs generally occurred in megacities with large
      populations, such as Guangzhou, Shanghai and Beijing. However, the summarized
      results suggested that industrial production and product consumption are the
      major sources of most PTSs in the urban environment, while unintentional emission
      during anthropogenic activities is an important contributor to airborne PTSs. It
      is important that fine particles serve as a major carrier of most airborne PTSs,
      which facilitates the long-range atmospheric transport (LRAT) of PTSs, and
      therefore, increases the exposure risk of the human body to these pollutants.
      This implied that not only the concentration and chemical composition of fine
      particles but also the absorbed PTSs are of particular concern when air pollution
      occurs.

PMID- 28745354
TI  - Soybean isoflavones ameliorate ischemic cardiomyopathy by activating Nrf2
      mediated antioxidant responses.
AB  - Ischemic cardiomyopathy (IC) is the major cause of heart failure. Conventional
      medicine has been proved ineffective with adverse effects. Soybean presents
      exciting adjunctive therapies and shows protective benefits for IC. However, the
      molecular mechanisms remain unclear. Isoflavones are the main bioactive
      components of soybean and may be protective against heart disease. Isoflavones
      were extracted by using an acidic-ethanol method and analyzed by HPLC. All
      patients with ischemic stroke were randomly and evenly assigned to two groups:
      the isoflavone group (80 mg day-1, n = 100) and control group (80 mg day-1
      placebo, n = 100), and the whole period of the experiment was 24 weeks. The
      effects of soybean isoflavone on brachial flow-mediated dilatation (FMD) were
      measured. HPLC fractionation shows that isoflavone extracts are mainly composed
      of 55% genistein, 23% daidzein, and 14% glycitein. Isoflavone therapy reduced
      more levels of triglyceride and LDL-c in females than in males. FMD was higher in
      the isoflavone group than in the control group after 24-week therapy (treatment
      effect 2.0%, 95% CI 0.18-3.0, P = 0.01). The baseline differences were adjusted
      in FMD and the isoflavone therapies were closely associated with the reduction of
      FMD impairment at 24 weeks (odds ratio 0.30, 95% CI 0.14-0.85, P = 0.01). The
      effects of isoflavone on brachial FMD were negatively associated with base FMD (r
      = -0.65, P < 0.01). Furthermore, isoflavone therapy caused a significant increase
      in the levels of erythroid-derived 2-like 2 (Nrf2), superoxide dismutase (SOD)
      and a significant decrease in serum levels of C-reactive protein, 8-isoprostane,
      malondialdehyde, interleukin-6 and tumor necrosis factor alpha. In contrast, the
      isoflavones had no effects on the levels of oxidation-related molecules when Nrf2
      was silenced. These results suggest that soybean isoflavones ameliorate IC
      patients by improving their antioxidant capacities via the upregulation of Nrf2.

PMID- 28745355
TI  - Half-sandwich iron(ii) complexes with protic acyclic diaminocarbene ligands:
      synthesis, deprotonation and metalation reactions.
AB  - A variety of half-sandwich iron(ii) complexes with diprotic acyclic
      diaminocarbene ligands (pADCs) have been obtained by reaction of the cationic
      complexes [Fe(Cp)(CO)2(CNR)]+ and [Fe(Cp)(CO)(CNR)2]+ with methylamine, and their
      acid-base behaviour was studied, revealing an easy reversible deprotonation
      reaction of both N-H moieties of the carbene ligands. The deprotonation process
      is frequently followed by a nucleophilic attack of the nitrogen atom on a vicinal
      carbonyl or isocyanide ligand, affording the corresponding metallacycles.
      Metalation of one or two N-H groups of the pADC ligands can be accomplished by
      reaction of the carbene complexes with either [AuCl(PPh3)] or [Ru(p-cym)Cl2]2 in
      the presence of KOH or LiHMDS as deprotonating agents. A number of Fe(ii)/Au(i)
      and Fe(ii)/Ru(ii) heterometallic complexes have been prepared in this way, some
      of them formally containing unique metalla-N-heterocyclic carbene ligands.

PMID- 28745356
TI  - An anionic Cd(ii) boron imidazolate framework with reversible structural
      transformation and biomolecular sensing properties.
AB  - An anionic Cd(ii) boron imidazolate framework (BIF-82) with gra topology has been
      synthesized by the targeted assembly of Cd(ii), the 1,3,5-benzenetricarboxylate
      ligand and the tetradentate boron imidazolate ligand, which shows reversible
      structural transformation, and it can encapsulate Ag nanoparticles into its
      structure for further sensing of cysteine.

PMID- 28745357
TI  - Defect induced p-type conductivity in zinc oxide at high temperature: electron
      paramagnetic resonance spectroscopy.
AB  - High-temperature electron paramagnetic resonance (EPR) measurements were applied
      to a ZnO nanocrystalline (50 nm) sample, synthesized via a solid co-precipitation
      method, in order to understand the behavior of intrinsic defect centers at high
      temperatures. It has been observed that the defect centers on the surface play a
      crucial role in the conductivity behavior of ZnO. Above 300  degrees C only
      surface defects can be visible in EPR spectra for ZnO nanocrystals which indicate
      p-type conductivity.

PMID- 28745358
TI  - Cross-talk between 10-gingerol and its anti-cancerous potential: a recent update.
AB  - Since time immortal, ginger, as an ancient herb, has been used throughout the
      world in foods and beverages due to its typical strong and pungent flavor.
      Besides its use as a spice, it also serves as an excellent source of several
      bioactive phenolics, including nonvolatile pungent compounds, such as gingerols,
      paradols, shogaols, and gingerones. Gingerols constitute key ingredients in fresh
      ginger, with the most abundant being 6-gingerol (6-G), 8-gingerol (8-G), and 10
      gingerol (10-G). Many studies have investigated the various valuable
      pharmacological properties of these ingredients and experimentally verified the
      mechanistic aspects of their health effects; however, to date, most research on
      the anti-cancerous activities of gingerols have focused largely on 6-G. Thus, the
      present article deals with the number of recent studies that have indicated and
      highlighted the role of 10-G with respect to its cancer prevention attributes in
      particular and its anti-inflammatory, anti-oxidant, anti-microbial, and
      gastrointestinal tract protective potential in general. The purpose of this
      review is to provide an overview of all the experimentally validated health
      benefits of 10-G for nutraceutical applications. The various findings have
      warranted the further investigation of 10-G and its possible use in various
      cancer treatments as well as its promising role as a chemo-preventive agent.

PMID- 28745359
TI  - Sequentially surface modified hematite enables lower applied bias
      photoelectrochemical water splitting.
AB  - Hematite (alpha-Fe2O3) is a suitable candidate for photoelectrochemical water
      splitting due to its well-suited band structure, stability, and availability.
      However, water splitting using a low external potential is the major challenge
      that limits the practical application of hematite. Here, we achieve a very low
      onset potential using a sequential surface treatment approach to overcome two
      fundamental limiting factors, sluggish hole transfer, and interfacial
      recombination, independently. First, a heavily doped Fe2-xSnxO3 surface
      passivation layer was created by Sn4+ surface treatment which can robustly
      inhibit interfacial recombination. Then, an NiOOH catalyst layer was deposited
      that greatly enhances the charge transfer process across the passivated
      electrode/electrolyte interface. By exploiting this approach, the optimized
      sequentially treated photoanode (Fe2O3/Fe2-xSnxO3/NiOOH) exhibits a low
      photocurrent onset potential of 0.49 V vs. RHE and a saturated photocurrent
      density of 2.4 mA cm-2 V at 1.5 V vs. RHE. Transient photocurrent and impedance
      spectroscopy measurements further reveal that the combined Fe2-xSnxO3/NiOOH
      layers reduce interfacial recombination and enhance charge transfer across the
      electrode/electrolyte interface. The results provide convincing evidence that it
      is possible to address the problems of surface trap recombination and sluggish
      catalysis independently by employing surface passivation layers first and
      catalysts later sequentially.

PMID- 28745360
TI  - Investigating synergistic interactions of group 4, 5 and 6 metals with gold
      nanoparticles for the catalysis of the electrochemical hydrogen evolution
      reaction.
AB  - An investigation of the catalysis of the electrochemical hydrogen evolution
      reaction (HER, 2H+ + 2e- -> H2) in aqueous 0.5 M H2SO4 electrolyte using
      composites consisting of gold nanoparticles (AuNP), carbon (Black Pearl 2000) and
      group 4, 5, and 6 metals is presented. This study is a continuation of our
      earlier work (Phys. Chem. Chem. Phys., 2016, 18, 21548-21553) on molybdenum and
      AuNP, which we found to interact synergistically to enhance the HER. We
      demonstrate here that tungsten not only also showed synergy with AuNP, but the
      extent of synergy is even larger than that of the Mo-AuNP composite. The average
      overpotential needed by the tungsten-based composite catalyst to drive a H2
      current density (jH2) of 10 mA cm-2 was 300 mV. In contrast, other metals such as
      Ti, Zr, V, Nb and Ta did not have any observable synergy with AuNP. Our
      experimental results indicate that the absence of synergy with these non
      performing composites could be related to the absorption of hydrogen into the
      bulk lattice of the metals to give hydrides. The strong binding of H to these
      metals could have also prevented their further reaction. We also propose that the
      aforementioned metal hydrides suppressed HER because they are ineffective for the
      initial proton discharge step.

PMID- 28745361
TI  - In silico genotoxicity of coumarins: application of the Phenol-Explorer food
      database to functional food science.
AB  - Coumarins are a group of phytochemicals that may be beneficial or harmful to
      health depending on their type and dosage and the matrix that contains them. Some
      of these compounds have been proven to display pro-oxidant and clastogenic
      activities. Therefore, in the current work, we have studied the coumarins that
      are present in food sources extracted from the Phenol-Explorer database in order
      to predict their clastogenic activity and identify the structure-activity
      relationships and genotoxic structural alerts using alternative methods in the
      field of computational toxicology. It was necessary to compile information on the
      type and amount of coumarins in different food sources through the analysis of
      databases of food composition available online. A virtual screening using a
      clastogenic model and different software, such as MODESLAB, ChemDraw and
      STATISTIC, was performed. As a result, a table of food composition was prepared
      and qualitative information from this data was extracted. The virtual screening
      showed that the esterified substituents inactivate molecules, while the methoxyl
      and hydroxyl substituents contribute to their activity and constitute, together
      with the basic structures of the studied subclasses, clastogenic structural
      alerts. Chemical subclasses of simple coumarins and furocoumarins were classified
      as active (xanthotoxin, isopimpinellin, esculin, scopoletin, scopolin and
      bergapten). In silico genotoxicity was mainly predicted for coumarins found in
      beer, sherry, dried parsley, fresh parsley and raw celery stalks. The results
      obtained can be interesting for the future design of functional foods and dietary
      supplements. These studies constitute a reference for the genotoxic
      chemoinformatic analysis of bioactive compounds present in databases of food
      composition.

PMID- 28745362
TI  - Superior acidic catalytic activity and stability of Fe-doped HTaWO6 nanotubes.
AB  - Fe-doped HTaWO6 (H1-3xFexTaWO6, x = 0.23) nanotubes as highly active solid acid
      catalysts were prepared via an exfoliation-scrolling-exchange process. The
      specific surface area and pore volume of undoped nanotubes (20.8 m2 g-1, 0.057
      cm3 g-1) were remarkably enhanced through Fe3+ ion-exchange (>100 m2 g-1, 0.547
      cm3 g-1). Doping Fe ions into the nanotubes endowed them with improved thermal
      stability due to the stronger interaction between the intercalated Fe3+ ions and
      the host layers. This interaction also facilitated the preservation of effective
      Bronsted acid sites and the generation of new acid sites. The integration of
      these functional roles resulted in Fe-doped nanotubes with high acidic catalytic
      activities in the Friedel-Crafts alkylation of anisole and the esterification of
      acetic acid. Facile accessibility to active sites, generation of effective
      Bronsted acid sites, high stability of the tubular structure and strong acid
      sites were found to synergistically contribute to the excellent acidic catalytic
      efficiency. Additionally, the activity of cycled nanocatalysts can be easily
      recovered through annealing treatment.

PMID- 28745363
TI  - Novel nanosensing technologies for exosome detection and profiling.
AB  - Exosomes have recently emerged as highly promising cancer biomarkers because they
      are abundant in biofluids, carry proteins and RNA reflecting their originating
      cells and are stable over weeks. Beyond abundance and stability, detailed exosome
      analyses could be clinically useful for diagnosing and profiling cancers. Despite
      their clinical potential, simple, reliable and sensitive approaches for rapidly
      quantifying exosomes and their molecular information has been challenging.
      Therefore, there is a clear need to develop next-generation sensing technologies
      for exosome detection and analysis. In this critical review, we will describe
      three nanotechnology sensing platforms developed for analysis of exosomal
      proteins and RNAs directly from clinical specimens and discuss future development
      to facilitate their translation into routine clinical use.

PMID- 28745364
TI  - Expediting dynamics approach to understand the influence of 14-3-3zeta causing
      metastatic cancer through the interaction of YAP1 and beta-TRCP.
AB  - The 14-3-3zeta protein acts as a molecular switch in regulating the TGF-beta
      pathway, which alters from a tumor suppressor in the early stage of breast cancer
      to a promoter of metastasis in the late stage. This change is due to the binding
      of 14-3-3zeta with YAP1 and beta-TRCP in premalignant and cancer cells,
      respectively. Owing to this inappropriate role of 14-3-3zeta when involved in
      cancer and metastasis, we predicted that Gln15, Glu17, Tyr211, and Gln219 are
      hotspot residues of 14-3-3zeta during its interaction with YAP1 protein.
      Similarly, we identified Gln15, Tyr211, Leu216, and Leu220 as hotspot residues of
      14-3-3zeta during its interaction with beta-TRCP protein. Targeting these
      residues of 14-3-3zeta can prevent cancer and metastasis caused by malfunctioning
      of the TGF-beta pathway. In this work, we also predicted that YAP1 is an
      intrinsically disordered protein (IDP), and such proteins bind with other
      proteins via either an induced fit or a conformational selection mechanism.
      Intuitively, we found that 14-3-3zeta has high affinity towards phosphorylated
      YAP1 at Ser127 rather than unphosphorylated YAP1, which is in close agreement
      with previously reported experimental works. Thus, we performed an analysis by
      molecular dynamics simulations to reveal the conformational changes in YAP1 after
      phosphorylation at the atomistic level. Our work clearly illustrates the effect
      of phosphorylation on YAP1 in terms of conformational changes and the regulation
      of its function.

PMID- 28745365
TI  - Elemental bio-imaging of PEGylated NaYF4:Yb/Tm/Gd upconversion nanoparticles in
      mice by laser ablation inductively coupled plasma mass spectrometry to study
      toxic side effects on the spleen, liver and kidneys.
AB  - Rare-earth upconversion nanoparticles (UCNPs) are considered stable nanoprobes
      with low toxicity and deep tissue penetration. However, the increasing use of
      UCNPs has raised concerns about their potential toxicity in living organisms.
      Very few studies have reported the toxicity of UCNPs; hence, it is not possible
      to conclude yet that UCNPs are safe. In this study, the distribution of PEGylated
      NaYF4:Yb/Tm/Gd nanoparticles (PEG-UCNPs) in female Balb/c mice following
      intravenous administration, and imaging in the spleen, liver and kidney was
      examined by laser ablation inductively coupled plasma mass spectrometry (LA-ICP
      MS). PEG-UCNPs distributed primarily to the liver and spleen, with significant
      but lower levels being noted in the kidneys, heart, and lungs. At the sub-organ
      level, PEG-UCNPs mainly accumulated within the red pulp of the spleen instead of
      the white pulp, which indicated that PEG-UCNPs are poorly immunogenic, or not
      immunogenic at all. The imaging of Cu in the liver and spleen showed that the
      primary clearance organ for PEG-UCNPs is the liver, although they are accumulated
      in the spleen rather than the liver. This can be explained by the fact that
      excess superoxide anions produced by phagocytosis of the PEG-UCNPs need Cu-Zn
      superoxide dismutase to be converted to hydrogen peroxide. From the Fe, Cu, and
      Zn imaging of the kidney, it was concluded that PEG-UCNPs do not exhibit
      nephrotoxicity.

PMID- 28745369
TI  - Chlorogenic acid protects against aluminium-induced cytotoxicity through
      chelation and antioxidant actions in primary hippocampal neuronal cells.
AB  - Chlorogenic acid (CGA), a major polyphenolic component of many plants, displays
      antioxidant and neuroprotective properties in neurodegenerative diseases. To
      investigate whether CGA may influence aluminium (Al) induced cytotoxicity,
      aluminium chloride (50 MUM Al) was administered in primary hippocampal neuronal
      cells presupplemented with CGA (10, 50 and 100 MUM). Our study shows that the
      exposure to Al caused cell death, Al3+ accumulation, reactive oxygen species
      generation and mitochondrial damage in cells. The administration of CGA (50 MUM)
      increased cell viability by 37.5%, decreased the levels of Al3+ by 26.0%,
      together with significantly weakening the oxidative damage compared with Al
      treatment alone. CGA protected neurons against Al-induced oxidative stress by
      increasing the expression of nuclear factor-E2-related factor 2 and its target
      phase 2 enzymes. The administration of CGA remarkably promoted the activities of
      superoxide dismutase, catalase, glutathione peroxidase, glutathione S
      transferase, creatine kinase and acetylcholinesterase and attenuated the rate of
      ATP hydrolysis. Our finding shows that CGA has neuroprotective effects against Al
      induced cytotoxicity by chelation and antioxidant activation.

PMID- 28745370
TI  - Bora-amidinate as a cooperative ligand in group 2 metal catalysis.
AB  - Syntheses and crystal structures of the monomeric bora-amidinate (bam) complexes
      DIPPNBN-Mg.(THF)3 and DIPPNBN-Ca.(THF)4 are presented; DIPPNBN = HB[N(2,6-iPr2
      C6H3)]2. The simplicity of their 1H NMR spectra in THF-d8 suggest that their
      monomeric solid state structures are retained in solution. DIPPNBN-Mg.(THF)3 in
      C6D6, however, is in equilibrium with a dimeric species. Calculations (B3PW91/6
      311++G**) reveal a very high localized negative charge (NPA: -1.103) on the N
      atoms in DIPPNBN-Mg. The strongly basic properties of the bam ligand are in
      agreement with catalytic activity of these complexes in the intramolecular alkene
      hydroamination. A mechanism is proposed in which the bam ligand is non-innocent
      and cooperative, playing an active role in substrate deprotonation and product
      protonation.

PMID- 28745371
TI  - Protein-induced fluorescence enhancement of two-photon excitable water-soluble
      diketopyrrolopyrroles.
AB  - Fluorescent contrast agents are important tools in cell biology and medical
      imaging due to their high sensitivity and relative availability.
      Diketopyrrolopyrrole (DPP) derivatives have been recently studied for
      applications in bioimaging, but certain drawbacks due to their inherent structure
      have stifled progress towards their widespread implementation. Aggregation caused
      quenching (ACQ) associated with pi-pi stacking in relatively rigid extended
      conjugation systems as well as hydrophobicity of previously reported DPPs make
      most unsuitable for biological imaging applications. Addressing these
      deficiencies, we report the synthesis and photophysical characterization of two
      new water-soluble diketopyrrolopyrole (DPP) probes that exhibit pronounced
      protein-induced fluorescence enhancement (PIFE) upon binding serum albumin
      protein. In vitro studies were also performed showing low cytotoxicity for the
      new DPP probes. Two-photon fluorescence microscopy (2PFM) images were obtained
      via excitation at 810 nm and emission in the NIR window of biological
      transparency, illustrating the potential of these compounds as nonlinear optical
      bioimaging probes.

PMID- 28745372
TI  - Systems-level organization of non-alcoholic fatty liver disease progression
      network.
AB  - Non-Alcoholic Fatty Liver Disease (NAFLD) is a complex spectrum of diseases
      ranging from simple steatosis to Non-Alcoholic Steatohepatitis (NASH) with
      fibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The
      pathogenesis of NAFLD is complex, involving crosstalk between multiple organs,
      cell-types, and environmental and genetic factors. Dysfunction of the adipose
      tissue plays a central role in NAFLD progression. Here, we analysed
      transcriptomics data obtained from the Visceral Adipose Tissue (VAT) of NAFLD
      patients to understand how the VAT metabolism is altered at the genome scale and
      co-regulated with other cellular processes during the progression from obesity to
      NASH with fibrosis. For this purpose, we performed Weighted Gene Co-expression
      Network Analysis (WGCNA), a method that organizes the disease transcriptome into
      functional modules of cellular processes and pathways. Our analysis revealed the
      coordination of metabolic and inflammatory modules (termed "immunometabolism") in
      the VAT of NAFLD patients. We found that genes of arachidonic acid, sphingolipid
      and glycosphingolipid metabolism were upregulated and co-expressed with genes of
      proinflammatory signalling pathways and hypoxia in NASH/NASH with fibrosis. We
      hypothesize that these metabolic alterations might play a role in sustaining VAT
      inflammation. Furthermore, immunometabolism related genes were also co-expressed
      with genes involved in Extracellular Matrix (ECM) degradation. Our analysis
      indicates that upregulation of both ECM degrading enzymes and their inhibitors
      (incoherent feedforward loop) potentially leads to the ECM deposition in the VAT
      of NASH with fibrosis patients.

PMID- 28745373
TI  - Facile synthesis of benzo[b]thiophenes via metal-free radical-triggered
      intramolecular C-S bond formation.
AB  - A facile method for the synthesis of benzo[b]thiophenes with good to excellent
      yields via metal-free intramolecular C-S bond formation has been developed by
      utilizing I2 as a catalyst and O2 from air as an oxidant (20 examples). Its
      notable features such as catalytic I2, intramolecular C-S bond formation, short
      reaction times, and broad functional group tolerance make this strategy highly
      attractive. The purification of products only needs washing with solvents,
      thereby avoiding traditional chromatography and recrystallization, which belongs
      to group-assisted purification (GAP) chemistry.

PMID- 28745376
TI  - Stereoselective synthesis of conformationally restricted KOR agonists based on
      the 2,5-diazabicyclo[2.2.2]octane scaffold.
AB  - It has been postulated that the KOR affinity depends on the dihedral angle of the
      ethylenediamine pharmacophore. Herein, 2,5-diazabicyclooctanes bearing a
      pyrrolidino moiety in the 7-position were envisaged to study KOR agonists with a
      conformationally rigid ethylenediamine pharmacophore and thus a defined
      N(pyrrolidine)-C7-C1-N2 dihedral angle. The first approach with an intramolecular
      addition at the chiral sulfinylimines 9 failed to give bicyclic products. The key
      step in the second approach was a Dieckmann analogous cyclization providing mixed
      methyl silyl ketals 11a-e as key intermediates. The highest KOR affinity was
      found for the 2,5-dibenzyl substituted derivatives (S,R,S)-16a (Ki = 31 nM) and
      (R,S,R)-16a (Ki = 74 nM) with the pyrrolidine ring oriented towards N-5. The high
      KOR affinity of (S,R,S)-16a is unexpected, since the KOR pharmacophoric
      ethylenediamine system adopts a dihedral angle of about 160 degrees , which is
      quite different from the angle of the energetically most favored conformer of the
      flexible and potent KOR agonist 2. (S,R,S)-16a represents a KOR agonist with
      moderate selectivity over MOR (8-fold) and DOR (5-fold), but high selectivity
      over both sigma receptor subtypes. In the [35S]GTPgammaS assay (S,R,S)-16a
      reacted as a full KOR agonist with an EC50 value of 240 nM.

PMID- 28745377
TI  - Ratcheting rotation or speedy spinning: EPR and dynamics of Sc3C2@C80.
AB  - Besides their technological applications, endohedral fullerenes provide ideal
      conditions for investigating molecular dynamics in restricted geometries. A
      representative of this class of systems, Sc3C2@C80 displays complex
      intramolecular dynamics. The motion of the 45Sc trimer has a remarkable effect on
      its electron paramagnetic resonance (EPR) spectrum, which changes from a
      symmetric 22-peak pattern at high temperature to a single broad lineshape at low
      temperature. The scandium trimer consists of two equivalent and one inequivalent
      metal atom, due to the carbon dimer rocking through the Sc3 triangle. We
      demonstrate through first-principles molecular dynamics (MD), EPR parameter
      tensor averaging, and spectral modelling that, at high temperatures, three
      dimensional movement of the enclosed Sc3C2 moiety takes place, which renders the
      metal centers equivalent and their magnetic parameters effectively isotropic. In
      contrast, at low temperatures the dynamics becomes restricted to two dimensions
      within the equatorial belt of the Ih symmetric C80 host fullerene. This restores
      the inequivalence of the scandium centers and causes their anisotropic hyperfine
      couplings to broaden the experimental spectrum.

PMID- 28745378
TI  - Cyanidin-3-O-beta-glucoside combined with its metabolite protocatechuic acid
      attenuated the activation of mice hepatic stellate cells.
AB  - Previous studies indicated that cyanidin-3-O-beta-glucoside (C3G) as a classical
      anthocyanin exerted an anti-fibrotic effect in the liver, but its bioavailability
      was quite low. This study was undertaken to explore the restraining effect of C3G
      and its metabolite protocatechuic acid (PCA) on the activation of hepatic
      stellate cells (HSCs). Our data demonstrated that the treatment of a carbon
      tetrachloride-treated mice model with C3G inhibited liver fibrosis and HSC
      activation. In vitro, both C3G and PCA preserved the lipid droplets and retinol
      in primary HSCs, and additionally inhibited the mRNA expression of alpha-smooth
      muscle actin and collagen I, but elevated the level of matrix metalloproteinase-2
      and liver X receptors. Only PCA suppressed the levels of tumor necrosis factor
      alpha (TNF-alpha) and interleukin-6 (IL-6) secreted from HSCs significantly. In
      addition, C3G and PCA inhibited the proliferation and migration of HSCs. In
      conclusion, PCA mainly explained the in vivo inhibiting effect of C3G on HSC
      activation and liver fibrosis.

PMID- 28745380
TI  - Bioactivity and chemical characterization of Opuntia macrorhiza Engelm. seed oil:
      potential food and pharmaceutical applications.
AB  - In the food industry, there is a continuous search for ingredients that might
      provide advantageous properties to food products, either considering their
      nutritional value or bioactivity, as well as flavouring and technological
      aspects. Crude oils are good examples of this type of ingredient, especially if
      obtained from nonconventional sources. Accordingly, the Opuntia macrorhiza
      Engelm. seed oil (OMSO) was chemically characterized and evaluated for different
      in vitro and in vivo bioactivities. OMSO presented physicochemical
      characteristics appropriate to be considered as an edible oil, namely low acidity
      value, stability to oxidation (high peroxide value and low K232 and K270 values),
      and high contents of unsaturated fatty acids (as shown by the iodine value) and
      saponifiable matter. Furthermore, this natural oil, owing to its rich
      phytochemical profile, showed relevant antioxidant activity (especially in lipid
      peroxidation inhibition assays), alpha-glucosidase inhibitory activity,
      cytotoxicity against human tumour cell lines, antibacterial (mainly against Gram
      positive species) and antifungal properties, as well as anti-inflammatory and
      analgesic activities. Furthermore, OMSO did not show any sign of acute toxicity
      on animals, highlighting its possible use in different applications, considering
      that this natural product is not expected to induce the adverse effects typically
      associated with synthetic bioactive agents (e.g., ampicillin, amphotericin B, or
      lysine acetylsalicilate).

PMID- 28745381
TI  - Toward a reverse hierarchy of halogen bonding between bromine and iodine.
AB  - We compare here the halogen bond characteristics of bimolecular adducts involving
      either N-bromo- or N-iodosaccharin as strong halogen bond donors, with 4-picoline
      as a common XB acceptor. In the NBSac.Pic system, the bromine atom of NBSac is
      displaced toward the picoline, almost at a median position between the two
      nitrogen atoms, NSac and N'Pic, with NSacBr and BrN'Pic distances at 2.073(6) and
      2.098(6) A respectively. This extreme situation contrasts with the analogous
      iodine derivative, NISac.Pic, where the NSac-I and IN'Pic distances amount to
      2.223(4) and 2.301(4) A respectively. Periodic DFT calculations, and molecular
      calculations of adducts (PBEPBE-D2 aug-cc-pVTZ) either at the experimental frozen
      geometry or with optimization of the halogen position, indicate a more important
      degree of covalency (i.e. shared-shell character) in the adduct formed with the
      bromine atom. A stronger charge transfer to the picoline is also found for the
      bromine (+0.27 |e|) than for the iodine (+0.18 |e|) system. This inversion of
      halogen bond strength between I and Br finds its origin in the strong covalent
      character of the interaction in these adducts, in line with the strength of
      covalent N-Br and N-I bonds. Detailed characterization of the critical points
      (CPs) of the L(r) = -?2rho(r) function along bonding directions has permitted the
      adducts to be distinguished and they can be respectively described as "neutral"
      NISac/Pic and "intermediate" NSac/Br/Pic, the latter with Br being close to
      formal equivalent NSacBr and BrN'Pic interactions but still more associated to
      the XB donor than to the picoline, as indicated by the topological and energetic
      properties of the rho(r) function at the bond critical points (BCPs).

PMID- 28745382
TI  - Complexation of sesquiterpene lactones with cyclodextrins: synthesis and effects
      on their activities on parasitic weeds.
AB  - Allelochemicals are safer, more selective and more active alternatives than
      synthetic agrochemicals for weed control. However, the low solubility of these
      compounds in aqueous media limits their use as agrochemicals. Herein, we propose
      the application of alpha-, beta- and gamma-cyclodextrins to improve the
      physicochemical properties and biological activities of three sesquiterpene
      lactones: dehydrocostuslactone, costunolide and (-)-alpha-santonin. Complexation
      was achieved by kneading and coprecipitation methods. Aqueous solubility was
      increased in the range 100-4600% and the solubility-phase diagrams suggested that
      complex formation had been successful. The results of the PM3 semiempirical
      calculations were consistent with the experimental results. The activities on
      etiolated wheat coleoptiles, Standard Target Species and parasitic weeds were
      improved. Cyclodextrins preserved or enhanced the activity of the three
      sesquiterpene lactones. Free cyclodextrins did not show significant activity and
      therefore the enhancement in activity was due to complexation. These results are
      promising for applications in agrochemical design.

PMID- 28745383
TI  - Reactivity of N-heterocyclic carbene-pyridine palladacyclopentadiene complexes
      toward halogen addition. The unpredictable course of the reaction.
AB  - As an extension of a previously published work we have reacted some
      palladacyclopentadiene complexes stabilized by bidentate N-heterocyclic carbene
      pyridine or monodentate N-heterocyclic carbene-pyridine and isocyanide ligands
      with the halogens I2 and Br2. All the bidentate and monodentate complexes react
      with halogens to give at first the expected sigma-coordinated butadienyl
      fragment. However, two of the less hindered NHC carbene-pyridine bidentate
      butadienyl iodo derivatives undergo a further rearrangement and novel Pd(ii)
      complexes characterized by a ten term coordinative ring were isolated and
      characterized. In the most favorable case we were able to carry out the kinetics
      of rearrangement and measure its reaction rate. Moreover, we have surmised a
      plausible mechanism on the basis of a dedicated computational approach and in one
      case the surprising structure characterized by the ten term coordinative ring was
      resolved by X-ray diffraction.

PMID- 28745385
TI  - Multiview Hilbert transformation in full-ring transducer array-based
      photoacoustic computed tomography.
AB  - Based on the photoacoustic (PA) effect, PA tomography directly measures specific
      optical absorption, i.e., absorbed optical energy per unit volume. We recently
      developed a full-ring ultrasonic transducer array-based photoacoustic computed
      tomography (PACT) system for small-animal whole-body imaging. The system has a
      full-view detection angle and high in-plane resolution (~100  MUm). However, due
      to the bandpass frequency response of the piezoelectric transducer elements and
      the limited elevational detection coverage of the full-ring transducer array, the
      reconstructed images present bipolar (i.e., both positive and negative) pixel
      values, which cause ambiguities in image interpretation for physicians and
      biologists. We propose a multiview Hilbert transformation method to recover the
      unipolar initial pressure for full-ring PACT. The effectiveness of the proposed
      algorithm was first validated by numerical simulations and then demonstrated with
      ex vivo mouse brain structural imaging and in vivo mouse whole-body imaging.

PMID- 28745386
TI  - Adaptation of the Nomophobia Questionnaire (NMP-Q) to Spanish in a sample of
      adolescents.
AB  - INTRODUCTION: Nomophobia is the fear of being out of mobile phone contact. People
      suffering from this anxiety disorder have feelings of stress and nervousness when
      access to their mobiles or computers is not possible. This work is an adaptation
      and validation study of the Spanish version of the Nomophobia Questionnaire (NMP
      Q). METHODOLOGY: The study included 306 students (46.1% males and 53.9% females)
      with ages ranging 13 to 19 years (Md=15.41+/-1.22). RESULTS: Exploratory factor
      analysis revealed four dimensions that accounted for 64.4% of total variance. The
      ordinal &#945;-value was 0.95, ranging from 0.75 to 0.92 across factors. Measure
      of stability was calculated by the testretest method (r=0.823). Indicators of
      convergence with the Spanish versions of the &#8220;Mobile Phone Problem Use
      Scale&#8221; (r=0.654) and the &#8220;Generalized Problematic Internet Use
      Scale&#8221; (r=0.531) were identified. Problematic mobile phone use patterns
      were examined taking the 15P, 80P and 95P percentiles as cut-off points. Scores
      of 39, 87 and 116 on NMP-Q corresponded to occasional, at-risk and problematic
      users, respectively. CONCLUSIONS: Psychometric analysis shows that the Spanish
      version of the NMP-Q is a valid and reliable tool for the study of nomophobia.

PMID- 28745387
TI  - Clinical and Psychosocial Characterization of At-Risk Mental State and Recent
      Onset Psychosis Patients from an Early Psychosis Program in Barcelona (Spain).
AB  - INTRODUCTION: This study aimed to describe and compare socio-demographic,
      background, treatment history, and service use, psychopathological and
      psychosocial characteristics of At-Risk Mental States (ARMS) and First-Episode
      Psychosis (FEP) patients from the Sant Pere Claver-Early Psychosis Program (SPC
      EPP) in Barcelona. METHODS: 43 ARMS-patients and 40 FEP-patients were assessed
      with several clinical and psychosocial measures at study baseline. RESULTS:
      Clinical and psychosocial characteristics of the SPC-EPP sample were comparable
      to those of previous early psychosis studies. Overall, the socio-demographic and
      clinical background characteristics appeared to be mostly similar between ARMS
      and FEP patients. As expected, groups differed on history of previous psychiatric
      hospitalizations and current psychiatric treatment. The age at onset of both
      unspecific and prodromal symptoms, and age of first specialized
      psychiatric/psychological treatment were earlier in ARMS than in FEP-patients.
      FEP-patients showed higher scores on positive symptoms, cognitive and greater
      overall symptom severity than ARMS-patients. ARMS-patients showed higher scores
      on mania, general psychopathology and a slightly lower premorbid functioning
      since earlyadolescence than FEP-patients. CONCLUSIONS: Findings support the
      notion that ARMSpatients who seek for help can be considered as already highly
      dysfunctional and in need of treatment, given that they already suffer from
      multiple mental and functional disturbances. This supports current health care
      efforts in providing early access to treatment to this population and signals the
      need to sustain pilot early detection efforts.

PMID- 28745388
TI  - Suicidal ideation and self-injurious behavior in adolescents with eating
      disorders.
AB  - INTRODUCTION: The presence of suicidal thoughts and self-injurious behaviors in
      patients with eating disorders (ED) is well-known; however, this association is
      currently not defined empirically. The aim of the study is to determine the
      prevalence of suicidal ideation and self-harm in adolescents with eating
      disorders. A second objective is to study the association between self-injurious
      behavior and suicidal ideation, severity of eating disorder symptoms and symptoms
      of depression and anxiety, motivation to change and perfectionism. METHODOLOGY:
      We evaluated 109 patients (mean age, 14.74 years (SD: 1.53); 87.2% female) using
      the Eating Disorder Inventory (EDI-2), the Beck Depression Inventory (BDI-II),
      the State-Trait Anxiety Inventory (STAI), the Child and Adolescent Perfectionism
      Scale (CAPS) and the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ).
      RESULTS: Forty-seven patients (43.1%) had suicidal ideation and 34 (31.2%), self
      injurious behavior. The presence of suicidal ideation did not discriminate
      between patients with or without self-injurious behavior. Patients who self-harm
      had significantly higher scores on all scales of the EDI-2, except for
      &#8220;maturity fears&#8221;, in the total scores of BDI-II, STAI and CAPS. An
      association between selfinjurious behavior and motivation to change was found.
      CONCLUSIONS: A significant percentage of adolescents with eating disorders
      present suicidal ideation and selfinjurious behavior, making the
      psychopathological profile of these patients more severe. The presence of
      suicidal ideation in adolescents with eating disorders does not necessarily imply
      that they have self-injurious behavior; rather, such behavior could be a result
      of the need to regulate intense negative emotions.

PMID- 28745389
TI  - Efficacy of cognitive rehabilitation of attention, executive functions, and
      working memory in psychotic disorders: A systematic review.
AB  - dies have postulated that it is the basis of the disease as evidenced by its
      independent and persistent quality and its relation to prognosis. Research on
      cognitive deficits in psychotic disorders has led to the development of
      intervention strategies for the cognitive rehabilitation of these patients.
      Attention, working memory, and executive functions are among the most widely
      affected functions and are closely related to the functionality of these
      patients. This work aims to study the effectiveness of cognitive rehabilitation
      targeting attention, executive functions, and working memory in people diagnosed
      with a psychotic disorder (mostly schizophrenia). An exhaustive search in PubMed
      and PsycINFO was conducted up to January 2016. All research papers that were
      included studied a therapeutic technique to improve one or more of the
      aforementioned functions in patients over age 16 years diagnosed with psychotic
      disorder. Studies with methodological diversity were included, which were
      afterwards organized by levels of evidence. Thirty-four papers were studied, from
      which we can conclude that cognitive rehabilitation of the aforementioned
      cognitive functions brings about improvements in cognition. As a result of the
      influence of cognitive rehabilitation on other variables such as social
      functioning and symptoms of the disease, the results are promising.

PMID- 28745390
TI  - Dandy-Walker variant and refractory psychosis.

PMID- 28745391
TI  - Radiosurgery in Obsessive-compulsive disorder, a case report.

PMID- 28745392
TI  - [Standard diagnostic and therapeutic approach to chronic hepatitis C virus (HCV)
      infection - guidelines].

PMID- 28745393
TI  - Beyond an oncogene, Lin28 is a master regulator of cancer progression.
AB  - The RNA binding protein Lin28 is increased in most human malignancies, and
      elevated Lin28 is a biomarker for poor prognosis and contributes to cancer
      progression. Lin28 functions as a master oncogene and is involved in almost all
      hallmarks of cancer. In this review, we summarize the aberrant molecular
      expression mechanisms and pathological roles of Lin28 in cancer progression.
      Moreover, we elaborate on the established molecular mechanisms, from the
      transcriptional level to the post-transcriptional and translational levels, by
      which Lin28 regulates cancer progression.

PMID- 28745394
TI  - Opioids for chronic non-cancer pain in children and adolescents.
AB  - BACKGROUND: Pain is a common feature of childhood and adolescence around the
      world, and for many young people, that pain is chronic. The World Health
      Organization guidelines for pharmacological treatments for children's persisting
      pain acknowledge that pain in children is a major public health concern of high
      significance in most parts of the world. While in the past, pain was largely
      dismissed and was frequently left untreated, views on children's pain have
      changed over time, and relief of pain is now seen as importantWe designed a suite
      of seven reviews on chronic non-cancer pain and cancer pain (looking at
      antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs,
      opioids, and paracetamol as priority areas) in order to review the evidence for
      children's pain utilising pharmacological interventions in children and
      adolescents.As the leading cause of morbidity in children and adolescents in the
      world today, chronic disease (and its associated pain) is a major health concern.
      Chronic pain (lasting three months or longer) can arise in the paediatric
      population in a variety of pathophysiological classifications: nociceptive,
      neuropathic, idiopathic, visceral, nerve damage pain, chronic musculoskeletal
      pain, and chronic abdominal pain, and other unknown reasons.Opioids are used
      worldwide for the treatment of pain. They bind to opioid receptors in the central
      nervous system (mu, kappa, delta, and sigma) and can be agonists, antagonists,
      mixed agonist-antagonists, or partial agonists. Opioids are generally available
      in healthcare settings across most high-income countries, but access may be
      restricted in low- and middle-income countries. For example, opioids currently
      available in the UK include: buprenorphine, codeine, fentanyl, hydromorphone,
      methadone, morphine, oxycodone, and tramadol. Opioids are used in varying doses
      (generally based on body weight for paediatric patients) by means of parenteral,
      transmucosal, transdermal, or oral administration (immediate release or modified
      release). To achieve adequate pain relief in children using opioids, with an
      acceptable grade of adverse effects, the recommended method is a lower dose
      gradually titrated to effect in the child. OBJECTIVES: To assess the analgesic
      efficacy and adverse events of opioids used to treat chronic non-cancer pain in
      children and adolescents aged between birth and 17 years, in any setting. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)
      via the Cochrane Library, MEDLINE via Ovid, and Embase via Ovid from inception to
      6 September 2016. We also searched the reference lists of retrieved studies and
      reviews, and searched online clinical trial registries. SELECTION CRITERIA:
      Randomised controlled trials, with or without blinding, of any dose and any
      route, treating chronic non-cancer pain in children and adolescents, comparing
      opioids with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed studies for eligibility. We planned to use
      dichotomous data to calculate risk ratio and number needed to treat, using
      standard methods. We assessed GRADE (Grading of Recommendations Assessment,
      Development and Evaluation) and planned to create a 'Summary of findings' table.
      MAIN RESULTS: No studies were eligible for inclusion in this review. We rated the
      quality of the evidence as very low. We downgraded the quality of evidence by
      three levels due to the lack of data reported for any outcome. AUTHORS'
      CONCLUSIONS: There was no evidence from randomised controlled trials to support
      or refute the use of opioids to treat chronic non-cancer pain in children and
      adolescents. We are unable to comment about efficacy or harm from the use of
      opioids to treat chronic non-cancer pain in children and adolescents.We know from
      adult randomised controlled trials that some opioids, such as morphine and
      codeine, can be effective in certain chronic pain conditions.This means that no
      conclusions could be made about efficacy or harm in the use of opioids to treat
      chronic non-cancer pain in children and adolescents.

PMID- 28745395
TI  - The Foreseeable Harms of Trump's Global Gag Rule.
AB  - As one of his first acts as President of the United States, Donald Trump signed
      an executive order reinstating a version of the global gag rule. Under this rule,
      US grantees are barred from receiving global health funding if they engage in
      abortion-related work: not only abortion services, but also abortion referrals
      and counseling or advocacy for the liberalization of abortion laws. Critics of
      the Trump global gag rule generally raise three classes of objections: (1) that
      the rule fails to accomplish its presumed objective of reducing the number of
      abortions; (2) that it negatively affects the health and well-being of
      individuals and populations in affected countries; and (3) that it interferes
      with governments' ability to meet their international obligations. In this
      commentary, we examine the scientific and policy bases for these criticisms.

PMID- 28745396
TI  - Alcohol intake and risk of nonmelanoma skin cancer: a systematic review and dose
      response meta-analysis.
AB  - Nonmelanoma skin cancer (NMSC) comprises mainly basal cell carcinoma (BCC) and
      cutaneous squamous cell carcinoma (cSCC). The association between alcohol intake
      and NMSC has been inconclusive; therefore the objective of this study is to
      quantify the relationship between alcohol intake and NMSC using meta-analyses. A
      systematic literature search of PubMed and Embase was performed on 30 October
      2016. Eligible articles were case-control or cohort studies that examined alcohol
      intake and risk of BCC or cSCC and reported relative risks (RRs) with 95%
      confidence intervals (CIs). Of the 307 articles identified, 13 case-control and
      cohort studies were included in the systematic review, including 95 241 NMSC
      cases (91 942 BCC and 3299 cSCC cases). A random-effects model was used to obtain
      summary RRs and 95% CIs for dose-response meta-analyses. For every 10-gram
      increase in ethanol intake per day, a positive association was found for both BCC
      (summary RR of 1.07; 95% CI 1.04-1.09) and cSCC (summary RR of 1.11; 95% CI 1.06
      1.16). While there was evidence suggesting a nonlinear association for BCC, it
      may be due to the sparse data at higher alcohol intake levels. This meta-analysis
      found evidence that alcohol drinking is positively associated with both BCC and
      cSCC risk in a dose-dependent manner. These results should be interpreted with
      caution due to potential residual confounding. Nonetheless, because alcohol
      drinking is a prevalent and modifiable behaviour, it could serve as an important
      public health target to reduce the global health burden of NMSC.

PMID- 28745397
TI  - Tempo and mode of performance evolution across multiple independent origins of
      adhesive toe pads in lizards.
AB  - Understanding macroevolutionary dynamics of trait evolution is an important
      endeavor in evolutionary biology. Ecological opportunity can liberate a trait as
      it diversifies through trait space, while genetic and selective constraints can
      limit diversification. While many studies have examined the dynamics of
      morphological traits, diverse morphological traits may yield the same or similar
      performance and as performance is often more proximately the target of selection,
      examining only morphology may give an incomplete understanding of evolutionary
      dynamics. Here, we ask whether convergent evolution of pad-bearing lizards has
      followed similar evolutionary dynamics, or whether independent origins are
      accompanied by unique constraints and selective pressures over macroevolutionary
      time. We hypothesized that geckos and anoles each have unique evolutionary tempos
      and modes. Using performance data from 59 species, we modified Brownian motion
      (BM) and Ornstein-Uhlenbeck (OU) models to account for repeated origins estimated
      using Bayesian ancestral state reconstructions. We discovered that adhesive
      performance in geckos evolved in a fashion consistent with Brownian motion with a
      trend, whereas anoles evolved in bounded performance space consistent with more
      constrained evolution (an Ornstein-Uhlenbeck model). Our results suggest that
      convergent phenotypes can have quite distinctive evolutionary patterns, likely as
      a result of idiosyncratic constraints or ecological opportunities.

PMID- 28745399
TI  - Average treatment effect of hepatic resection versus locoregional therapies for
      hepatocellular carcinoma.
AB  - BACKGROUND: When comparing the efficacy of surgical and non-surgical therapies
      for hepatocellular carcinoma (HCC), a major limitation is the causal inference
      problem. This concerns the impossibility of seeing both outcomes of two different
      treatments for the same individual at the same time because one is inevitably
      missing. This aspect can be addressed methodologically by estimating the so
      called average treatment effect (ATE). METHODS: To estimate the ATE of hepatic
      resection over locoregional therapies for HCC, data from patients treated in two
      tertiary care settings between August 2000 and December 2014 were used to obtain
      counterfactual outcomes using an inverse probability weight survival adjustment.
      RESULTS: A total of 1585 patients were enrolled: 815 underwent hepatic resection,
      337 radiofrequency ablation (RFA) and 433 transarterial chemoembolization (TACE).
      The option of operating on all patients who had tumour ablation returned an ATE
      of +9.8 months for resection (effect size 0.111; adjusted P = 0.064). The option
      of operating on all patients who had TACE returned an ATE of +27.9 months (effect
      size 0.383; adjusted P < 0.001). The ATE of surgery was negligible in patients
      undergoing ablation for very early HCCs (effect size 0.027; adjusted P = 0.627),
      independently of albumin-bilirubin (ALBI) grade; or in patients with ALBI liver
      function grade 2 (effect size 0.083; adjusted P = 0.213), independently of tumour
      stage. In all other instances, the ATE of surgery was notably greater. Operating
      on patients who had TACE with multinodular HCC beyond the Milan criteria resulted
      in a mild ATE (effect size 0.140; adjusted P = 0.037). CONCLUSION: ATE estimation
      suggests that hepatic resection is a better treatment option than ablation and
      TACE in patients with HCC.

PMID- 28745400
TI  - Voxel-based magnetic resonance image postprocessing in epilepsy.
AB  - OBJECTIVE: Although the general utility of voxel-based processing of structural
      magnetic resonance imaging (MRI) data for detecting occult lesions in focal
      epilepsy is established, many differences exist among studies, and it is unclear
      which processing method is preferable. The aim of this study was to compare the
      ability of commonly used methods to detect epileptogenic lesions in magnetic
      resonance MRI-positive and MRI-negative patients, and to estimate their
      diagnostic yield. METHODS: We identified 144 presurgical focal epilepsy patients,
      15 of whom had a histopathologically proven and MRI-visible focal cortical
      dysplasia; 129 patients were MRI negative with a clinical hypothesis of seizure
      origin, 27 of whom had resections. We applied four types of voxel-based
      morphometry (VBM), three based on T1 images (gray matter volume, gray matter
      concentration, junction map [JM]) and one based on normalized fluid-attenuated
      inversion recovery (nFSI). Specificity was derived from analysis of 50 healthy
      controls. RESULTS: The four maps had different sensitivity and specificity
      profiles. All maps showed detection rates for focal cortical dysplasia patients
      (MRI positive and negative) of >30% at a strict threshold of p < 0.05 (family
      wise error) and >60% with a liberal threshold of p < 0.0001 (uncorrected), except
      for gray matter volume (14% and 27% detection rate). All maps except nFSI showed
      poor specificity, with high rates of false-positive findings in controls. In the
      MRI-negative patients, absolute detection rates were lower. A concordant nFSI
      finding had a significant positive odds ratio of 7.33 for a favorable
      postsurgical outcome in the MRI-negative group. Spatial colocalization of JM and
      nFSI was rare, yet showed good specificity throughout the thresholds.
      SIGNIFICANCE: All VBM variants had specific diagnostic properties that need to be
      considered for an adequate interpretation of the results. Overall, structural
      postprocessing can be a useful tool in presurgical diagnostics, but the low
      specificity of some maps has to be taken into consideration.

PMID- 28745401
TI  - Trimethylamine N-oxide: breathe new life.
AB  - : Association between elevated levels of systemic trimethylamine N-oxide (TMAO)
      and increased risk for adverse cardiovascular events have been proposed in recent
      years. Increasing experimental and clinical evidence in the last decade has
      implicated TMAO as an important contributor to the pathogenesis of cardiovascular
      diseases. TMAO, the oxygenated product of trimethylamine (TMA), belongs to the
      class of amine oxides. Most of the TMA derived from the metabolism of choline and
      L-carnitine by gut bacteria is absorbed into the bloodstream and gets rapidly
      oxidized to TMAO by the hepatic enzyme, flavin-containing monooxgenase-3. Here,
      we discussed the biosynthesis of TMAO and clinical studies that have assessed
      TMAO as a biomarker for various cardiovascular and other diseases such as kidney
      failure, thrombosis, atherosclerosis, obesity, diabetes and cancer. We also
      summarized the interaction of TMAO with synthetic and traditional molecules that
      together affect circulating TMAO levels. LINKED ARTICLES: This article is part of
      a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To
      view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

PMID- 28745402
TI  - Fat-based registration of breast dynamic contrast enhanced water images.
AB  - PURPOSE: In this study, a 3D fat-based deformable registration algorithm was
      developed for registering dynamic contrast-enhanced breast images. METHODS: The
      mutual information similarity measure with free-form deformation motion
      correction in rapidly enhancing lesions can introduce motion. However, in Dixon
      based fat-water separated acquisitions, the nonenhancing fat signal can directly
      be used to estimate deformable motion, which can be later used to deform the
      water images. Qualitative comparison of the fat-based registration method to a
      water-based registration method, and to the unregistered images, was performed by
      two experienced readers. Quantitative analysis of the registration was evaluated
      by estimating the mean-squared signal difference on the fat images. RESULTS:
      Using a scale of 0 (no motion) to 2 ( > 4 voxels of motion), the average image
      quality score of the fat-based registered images was 0.5 +/- 0.6, water-based
      registration was 0.8 +/- 0.8, and the unregistered dataset was 1.6 +/- 0.6. The
      mean-squared-signal-difference metric on the fat images was significantly lower
      for fat-based registered images compared with both water-based registered and
      unregistered images. CONCLUSIONS: Fat-based registration of breast dynamic
      contrast-enhanced images is a promising technique for performing deformable
      motion correction of breast without introducing new motion. Magn Reson Med
      79:2408-2414, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 28745403
TI  - Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
AB  - BACKGROUND: The UK abdominal aortic aneurysm (AAA) screening programmes currently
      invite only men for screening because the benefit in women is uncertain.
      Perioperative risk is critical in determining the effectiveness of screening, and
      contemporary estimates of these risks in women are lacking. The aim of this study
      was to compare mortality following AAA repair between women and men in the UK.
      METHODS: Anonymized data from the UK National Vascular Registry (NVR) for
      patients undergoing AAA repair (January 2010 to December 2014) were analysed. Co
      variables were extracted for analysis by sex. The primary outcome measure was in
      hospital mortality. Secondary outcome measures included mortality by 5-year age
      groups and duration of hospital stay. Logistic regression was performed to adjust
      for age, calendar time, AAA diameter and smoking status. NVR-based outcomes were
      checked against Hospital Episode Statistics (HES) data. RESULTS: A total of 23
      245 patients were included (13.0 per cent women). Proportionally, more women than
      men underwent open repair. For elective open AAA repair, the in-hospital
      mortality rate was 6.9 per cent in women and 4.0 per cent in men (odds ratio (OR)
      1.48, 95 per cent c.i. 1.08 to 2.02; P = 0.014), whereas for elective
      endovascular AAA repair it was 1.8 per cent in women and 0.7 per cent in men (OR
      2.86, 1.72 to 4.74; P < 0.001); the results in HES were similar. For ruptured
      AAA, there was no sex difference in mortality within the NVR; however, in HES,
      for ruptured open AAA repair, the in-hospital mortality rate was higher in women
      (33.6 versus 27.1 per cent; OR 1.36, 1.16 to 1.59; P < 0.001). CONCLUSION: Women
      have a higher in-hospital mortality rate than men after elective AAA repair even
      after adjustment. This higher mortality may have an impact on the benefit offered
      by any screening programme offered to women.

PMID- 28745405
TI  - Streptococcus agalactiae Multilocus sequence type 261 is associated with
      mortalities in the emerging Ghanaian tilapia industry.

PMID- 28745404
TI  - Testicular oocytes in smallmouth bass in northeastern Minnesota in relation to
      varying levels of human activity.
AB  - Testicular oocytes (TOs) have been found in black bass (Micropterus spp.) from
      many locations in North America. The presence of TOs is often assumed to imply
      exposure to estrogenic endocrine disrupting compounds (EDCs); however, a
      definitive causal relationship has yet to be established, and TO prevalence is
      not consistently low in fish from areas lacking evident EDC sources. This might
      indicate any of a number of situations: 1) unknown or unidentified EDCs or EDC
      sources, 2) induction of TOs by other stressors, or 3) testicular oocytes
      occurring spontaneously during normal development. In the present study, we
      analyzed TO occurrence in smallmouth bass (Micropterus dolomieu) from 8
      populations in northeastern Minnesota watersheds with differing degrees of human
      development and, hence, presumed likelihood of exposure to anthropogenic
      chemicals. Three watersheds were categorized as moderately developed, based on
      the presence of municipal wastewater discharges and higher human population
      density (4-81 per km2 ), and 5 watersheds were minimally developed, with very low
      human population density (0-1 per km2 ) and minimal built environment. Testicular
      tissues from mature fish were evaluated using a semiquantitative method that
      estimated TO density, normalized by cross-sectional area. Testicular oocyte
      prevalence and density among populations from moderately developed watersheds was
      higher than in populations from minimally developed watersheds. However, TO
      prevalence was unexpectedly high and variable (7-43%) in some populations from
      minimally developed watersheds, and only weak evidence was found for a
      relationship between TO density and watershed development, suggesting alternative
      or more complex explanations for TO presence in smallmouth bass from this region.
      Environ Toxicol Chem 2017;36:3424-3435. (c) 2017 SETAC.

PMID- 28745406
TI  - Highly Luminescent 2D-Type Slab Crystals Based on a Molecular Charge-Transfer
      Complex as Promising Organic Light-Emitting Transistor Materials.
AB  - A new 2:1 donor (D):acceptor (A) mixed-stacked charge-transfer (CT) cocrystal
      comprising isometrically structured dicyanodistyrylbenzene-based D and A
      molecules is designed and synthesized. Uniform 2D-type morphology is manifested
      by the exquisite interplay of intermolecular interactions. In addition to its
      appealing structural features, unique optoelectronic properties are unveiled.
      Exceptionally high photoluminescence quantum yield (PhiF ~ 60%) is realized by
      non-negligible oscillator strength of the S1 transition, and rigidified 2D-type
      structure. Moreover, this luminescent 2D-type CT crystal exhibits balanced
      ambipolar transport (uh and ue of ~10-4 cm2 V-1 s-1 ). As a consequence of such
      unique optoelectronic characteristics, the first CT electroluminescence is
      demonstrated in a single active-layered organic light-emitting transistor (OLET)
      device. The external quantum efficiency of this OLET is as high as 1.5% to
      suggest a promising potential of luminescent mixed-stacked CT cocrystals in OLET
      applications.

PMID- 28745407
TI  - Catalytic Dehydrogenative Coupling of Hydrosilanes with Alcohols for the
      Production of Hydrogen On-demand: Application of a Silane/Alcohol Pair as a
      Liquid Organic Hydrogen Carrier.
AB  - The compound [Ru(p-cym)(Cl)2 (NHC)] is an effective catalyst for the room
      temperature coupling of silanes and alcohols with the concomitant formation of
      molecular hydrogen. High catalyst activity is observed for a variety of
      substrates affording quantitative yields in minutes at room temperature and with
      a catalyst loading as low as 0.1 mol %. The coupling reaction is
      thermodynamically and, in the presence of a Ru complex, kinetically favourable
      and allows rapid molecular hydrogen generation on-demand at room temperature,
      under air, and without any additive. The pair silane/alcohol is a potential
      liquid organic hydrogen carrier (LOHC) for energy storage over long periods in a
      safe and secure way. Silanes and alcohols are non-toxic compounds and do not
      require special handling precautions such as high pressure or an inert
      atmosphere. These properties enhance the practical applications of the pair
      silane/alcohol as a good LOHC in the automotive industry. The variety and
      availability of silanes and alcohols permits a pair combination that fulfils the
      requirements for developing an efficient LOHC.

PMID- 28745408
TI  - A case of frontotemporal dementia with sexual disinhibition controlled by
      aripiprazole.

PMID- 28745409
TI  - Assessment of Reynolds stress components and turbulent pressure loss using 4D
      flow MRI with extended motion encoding.
AB  - PURPOSE: To measure the Reynolds stress tensor using 4D flow MRI, and to evaluate
      its contribution to computed pressure maps. METHODS: A method to assess both
      velocity and Reynolds stress using 4D flow MRI is presented and evaluated. The
      Reynolds stress is compared by cross-sectional integrals of the Reynolds stress
      invariants. Pressure maps are computed using the pressure Poisson equation-both
      including and neglecting the Reynolds stress. RESULT: Good agreement is seen for
      Reynolds stress between computational fluid dynamics, simulated MRI, and MRI
      experiment. The Reynolds stress can significantly influence the computed pressure
      loss for simulated (eg, -0.52% vs -15.34% error; P < 0.001) and experimental (eg,
      306 +/- 11 vs 203 +/- 6 Pa; P < 0.001) data. A 54% greater pressure loss is seen
      at the highest experimental flow rate when accounting for Reynolds stress (P <
      0.001). CONCLUSION: 4D flow MRI with extended motion-encoding enables
      quantification of both the velocity and the Reynolds stress tensor. The
      additional information provided by this method improves the assessment of
      pressure gradients across a stenosis in the presence of turbulence. Unlike
      conventional methods, which are only valid if the flow is laminar, the proposed
      method is valid for both laminar and disturbed flow, a common presentation in
      diseased vessels. Magn Reson Med 79:1962-1971, 2018. (c) 2017 International
      Society for Magnetic Resonance in Medicine.

PMID- 28745410
TI  - Short- and medium-term outcomes following primary ileocaecal resection for
      Crohn's disease in two specialist centres.
AB  - BACKGROUND: Despite improvements in medical therapy, the majority of patients
      with Crohn's disease still require surgery. The aim of this study was to report
      safety, and clinical and surgical recurrence rates, including predictors of
      recurrence, after ileocaecal resection for Crohn's disease. METHODS: This was a
      cohort analysis of consecutive patients undergoing a first ileocaecal resection
      for Crohn's disease between 1998 and 2013 at one of two specialist centres.
      Anastomotic leak rate and associated risk factors were assessed. Kaplan-Meier
      estimates were used to describe long-term clinical and surgical recurrence.
      Univariable and multivariable regression analyses were performed to identify risk
      factors for both endpoints. RESULTS: In total, 538 patients underwent primary
      ileocaecal resection (40.0 per cent male; median age at surgery 31 (i.q.r. 24-42)
      years). Median follow-up was 6 (2-9) years. Fifteen of 507 patients (3.0 per
      cent) developed an anastomotic leak. An ASA fitness grade of III (odds ratio (OR)
      4.34, 95 per cent c.i. 1.12 to 16.77; P = 0.033), preoperative antitumour
      necrosis factor therapy (OR 3.30, 1.09 to 9.99; P = 0.035) and length of resected
      bowel specimen (OR 1.06, 1.03 to 1.09; P < 0.001) were significant risk factors
      for anastomotic leak. Rates of clinical recurrence were 17.6, 45.4 and 55.0 per
      cent after 1, 5 and 10 years respectively. Corresponding rates of requirement for
      further surgery were 0.6, 6.5 and 19.1 per cent. Smoking (hazard ratio (HR) 1.67,
      95 per cent c.i. 1.14 to 2.43; P = 0.008) and a positive microscopic resection
      margin (HR 2.16, 1.46 to 3.21; P < 0.001) were independent risk factors for
      clinical recurrence. Microscopic resection margin positivity was also a risk
      factor for further surgery (HR 2.99, 1.36 to 6.54; P = 0.006). CONCLUSION:
      Ileocaecal resection achieved durable medium-term remission, but smoking and
      resection margin positivity were risk factors for recurrence.

PMID- 28745411
TI  - A Hollow-Structured CuS@Cu2 S@Au Nanohybrid: Synergistically Enhanced
      Photothermal Efficiency and Photoswitchable Targeting Effect for Cancer
      Theranostics.
AB  - It is of great importance in drug delivery to fabricate multifunctional
      nanocarriers with intelligent targeting properties, for cancer diagnosis and
      therapy. Herein, hollow-structured CuS@Cu2 S@Au nanoshell/satellite nanoparticles
      are designed and synthesized for enhanced photothermal therapy and
      photoswitchable targeting theranostics. The remarkably improved photothermal
      conversion efficiency of CuS@Cu2 S@Au under 808 nm near-infrared (NIR) laser
      irradiation can be explained by the reduced bandgap and more circuit paths for
      electron transitions for CuS and Cu2 S modified with Au nanoparticles, as
      calculated by the Vienna ab initio simulation package, based on density
      functional theory. By modification of thermal-isomerization RGD targeting
      molecules and thermally sensitive copolymer on the surface of nanoparticles, the
      transition of the shielded/unshielded mode of RGD (Arg-Gly-Asp) targeting
      molecules and shrinking of the thermally sensitive polymer by NIR photoactivation
      can realize a photoswitchable targeting effect. After loading an anticancer drug
      doxorubicin in the cavity of CuS@Cu2 S@Au, the antitumor therapy efficacy is
      greatly enhanced by combining chemo- and photothermal therapy. The reported
      nanohybrid can also act as a photoacoustic imaging agent and an NIR thermal
      imaging agent for real-time imaging, which provides a versatile platform for
      multifunctional theranostics and stimuli-responsive targeted cancer therapy.

PMID- 28745412
TI  - Edge Sites with Unsaturated Coordination on Core-Shell Mn3 O4 @Mnx Co3-x O4
      Nanostructures for Electrocatalytic Water Oxidation.
AB  - Transition-metal oxides are extensively investigated as efficient
      electrocatalysts for the oxygen evolution reaction (OER). However, large-scale
      applications remain challenging due to their moderate catalytic activity.
      Optimized regulation of surface states can lead to improvement of catalytic
      properties. Here, the design of Mn@Cox Mn3-x O4 nanoparticles with abundant edge
      sites via a simple seed-mediated growth strategy is described. The unsaturated
      coordination generated on the edge sites of Cox Mn3-x O4 shells makes a positive
      contribution to the surface-structure tailoring. Density functional theory
      calculations indicate that the edge sites with unsaturated coordination exhibit
      intense affinity for OH- in the alkaline electrolyte, which greatly enhances the
      electrochemical OER performance of the catalysts. The resulting Mn@Cox Mn3-x O4
      catalysts yield a current density of 10 mA cm-2 at an overpotential of 246 mV and
      a relatively low Tafel slope of 46 mV dec-1 . The successful synthesis of these
      metal oxides nanoparticles with edge sites may pave a new path for rationally
      fabricating efficient OER catalysts.

PMID- 28745413
TI  - A Simple Optoelectronic Tongue Discriminates Amino Acids.
AB  - A self-assembled nine-element optoelectronic tongue consisting of a positively
      charged water-soluble poly(para-phenyleneethynylene) and three metal ions (Fe2+ ,
      Co2+ , and Cu2+ ) at three different pH values (7, 10, and 13) discriminates all
      of the 20 natural amino acids in water. Unknown identification was not ideal.
      Addition of a highly positively charged green fluorescent protein in the presence
      of Fe2+ , Co2+ , and Cu2+ increased the unknown identification to above 86 %.
      Linear discriminant analysis (LDA) orders the responses according to the amino
      acid type, that is, hydrophobic, polar, anionic, or cationic.

PMID- 28745414
TI  - Right and left ventricular 24-segment sphericity index is abnormal in small-for
      gestational-age fetuses.
AB  - OBJECTIVE: Fetuses with growth restriction have been reported to have an abnormal
      sphericity index (SI), which is indicative of the shape of the ventricular
      chambers of the heart. Our aim was to evaluate the SI for 24 transverse segments
      distributed from base to apex of the right (RV) and left (LV) ventricles to
      determine whether, in small-for-gestational-age (SGA) fetuses, the SI is abnormal
      at locations other than the basal segment. METHODS: We evaluated 30 SGA fetuses
      between 25 and 37 weeks of gestation. SI was computed for both ventricles by
      dividing the end-diastolic mid-basal-apical length by each of 24 end-diastolic
      transverse segmental widths, from base (Segment 1) to apex (Segment 24). For each
      ventricle, the Z-score and centile for the SI from each of the 24 segments were
      computed using the mean and SD from published equations. The 24-segment method,
      defining abnormal SI as values < 10th centile or > 90th centile, was compared
      with that of using only the basal segment by chi-square analysis to determine the
      number of fetuses identified with an abnormal SI. RESULTS: In 23 of the 30 (77%)
      SGA fetuses, at least one of the 24 transverse segments in one or both ventricles
      had an abnormal SI; in 17% of cases, both ventricles were affected, in 23% of
      cases only the RV was involved and in 37% of cases only the LV was involved.
      Compared with the 24-segment model, significantly fewer fetuses with an abnormal
      SI were identified using only basal Segment 1, from the RV base (58%, 7/12; P <
      0.01) or only Segment 12, in the mid portion of the RV (50%, 6/12; P < 0.005).
      Combining measurements of Segment 1 and Segment 12 from the RV identified 83% of
      fetuses with at least one abnormal SI and was not significantly different from
      using the 24-segment model. Similarly, significantly fewer fetuses with an
      abnormal SI were identified using only LV basal Segment 1 (63%, 10/16; P < 0.006)
      or only Segment 12, in the mid portion of the LV (75%, 12/16; P < 0.03), when
      compared with the 24-segment model. Combining measurements of both LV Segment 1
      and Segment 12 identified 81% (13/16) of fetuses with an abnormal SI and was not
      significantly different from using the 24-segment model. CONCLUSION: The 24
      segment SI of RV and LV provides a comprehensive method with which to examine the
      shape of the ventricular chambers and identifies more SGA fetuses with an
      abnormal SI than are identified using only the basal segment SI. Copyright (c)
      2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28745415
TI  - Self-reported psychiatric symptoms associated with anticipated close psychiatry
      follow-up and/or hospitalization status in geriatric psychiatry patients: a
      preliminary study.

PMID- 28745416
TI  - A role for host cell exocytosis in InlB-mediated internalisation of Listeria
      monocytogenes.
AB  - The bacterial surface protein InlB mediates internalisation of Listeria
      monocytogenes into human cells through interaction with the host receptor
      tyrosine kinase, Met. InlB-mediated entry requires localised polymerisation of
      the host actin cytoskeleton. Apart from actin polymerisation, roles for other
      host processes in Listeria entry are unknown. Here, we demonstrate that
      exocytosis in the human cell promotes InlB-dependent internalisation. Using a
      probe consisting of VAMP3 with an exofacial green fluorescent protein tag, focal
      exocytosis was detected during InlB-mediated entry. Exocytosis was dependent on
      Met tyrosine kinase activity and the GTPase RalA. Depletion of SNARE proteins by
      small interfering RNA demonstrated an important role for exocytosis in Listeria
      internalisation. Depletion of SNARE proteins failed to affect actin filaments
      during internalisation, suggesting that actin polymerisation and exocytosis are
      separable host responses. SNARE proteins were required for delivery of the human
      GTPase Dynamin 2, which promotes InlB-mediated entry. Our results identify
      exocytosis as a novel host process exploited by Listeria for infection.

PMID- 28745417
TI  - Secondary Metabolite Production from Industrially Relevant Bacteria is Enhanced
      by Organic Nanofibers.
AB  - Streptomycetes are exploited for the production of a wide range of secondary
      metabolites, including antibiotics. Therefore, both academic and industrial
      research efforts are focused on enhancing production of these precious
      metabolites. So far, this has been mostly achieved by classical or recombinant
      genetic techniques, in association with process optimization for either submerged
      or solid state fermentation. New cultivation approaches addressing the natural
      mycelial growth and life cycle would allow the biosynthetic potential of
      filamentous strains to be much better exploited. We developed a cultivation
      system for antibiotic-producing microorganisms which involves electrospun organic
      nanofibers deposited onto agar plates or immersed in liquid media. Dense
      filamentous networks of branched hyphae formed by bacterial colonies were found
      to wrapped around the fibers. We analyzed the effects of fibers on growth and
      antibiotic production in Streptomyces lividans, and found that the actinorhodin,
      undecylprodigiosin and calcium dependent antibiotic productions were positively
      modulated, with a two- to sixfold enhancement compared to standard culture
      conditions. Highlighting the secondary metabolism-promoting role of nanofibers in
      bacterial cultures, these results open a route to the design of improved culture
      systems for microorganisms based on organic nanostructures.

PMID- 28745418
TI  - Insights into the Hydrogen-Atom Transfer of the Blue Aroxyl.
AB  - An experimental and theoretical study on hydrogen-atom transfer dynamics in the
      hydrogen-bonded substituted phenol/phenoxyl complex of the blue aroxyl (2,4,6-tri
      tert-butylphenoxyl) is presented. The experimental exchange dynamics is
      determined in different organic solvents from the temperature-dependent
      alternating line-width effect in the continuous-wave ESR spectrum. From bent
      Arrhenius plots, effective tunnelling contributions with parallel heavy-atom
      motion are concluded. To clarify the transfer mechanism, reaction paths for
      different conformers of the substituted phenol/phenoxyl complex are modelled
      theoretically. Various DFT and post-Hartree-Fock methods including multireference
      methods are applied. From the comparison of experimental and theoretical data it
      is concluded that the system favours concerted hydrogen-atom transfer along a
      parabolic reaction path caused by heavy-atom motion.

PMID- 28745419
TI  - Picomolar Traces of Americium(III) Introduce Drastic Changes in the Structural
      Chemistry of Terbium(III): A Break in the "Gadolinium Break".
AB  - The crystallization of terbium 5,5'-azobis[1H-tetrazol-1-ide] (ZT) in the
      presence of trace amounts (ca. 50 Bq, ca. 1.6 pmol) of americium results in 1)
      the accumulation of the americium tracer in the crystalline solid and 2) a
      material that adopts a different crystal structure to that formed in the absence
      of americium. Americium-doped [Tb(Am)(H2 O)7 ZT]2 ZT?10 H2 O is isostructural to
      light lanthanide (Ce-Gd) 5,5'-azobis[1H-tetrazol-1-ide] compounds, rather than to
      the heavy lanthanide (Tb-Lu) 5,5'-azobis[1H-tetrazol-1-ide] (e.g., [Tb(H2 O)8 ]2
      ZT3 ?6 H2 O) derivatives. Traces of Am seem to force the Tb compound into a
      structure normally preferred by the lighter lanthanides, despite a 108 -fold Tb
      excess. The americium-doped material was studied by single-crystal X-ray
      diffraction, vibrational spectroscopy, radiochemical neutron activation analysis,
      and scanning electron microcopy. In addition, the inclusion properties of terbium
      5,5'-azobis[1H-tetrazol-1-ide] towards americium were quantified, and a model for
      the crystallization process is proposed.

PMID- 28745420
TI  - Reasons for (not) discontinuing antipsychotics in dementia.
AB  - BACKGROUND: The gap between high antipsychotic prescription rates for patients
      with dementia and the guidelines' advice to prescribe cautiously indicates that
      barriers to discontinuation exist. This exploratory study used the theory of
      planned behaviour to give a first overview of the factors that influence
      physicians to discontinue antipsychotics in nursing home patients with dementia.
      METHODS: Forty-one physicians in the Netherlands completed an online survey based
      on the theory of planned behaviour. RESULTS: Half of the respondents agreed that
      antipsychotics have positive consequences for patients, such as calming effects.
      Physicians who indicated that they tend not to discontinue antipsychotics believe
      that antipsychotics are associated with positive consequences for nursing home
      staff. Physicians who tend to discontinue antipsychotics had a higher perceived
      behavioural control than those who indicated having a low intention. CONCLUSION:
      To enhance discontinuation of antipsychotics, interventions should focus on both
      patient-related factors and staff-related factors. Prescribing decisions are
      influenced by staff-related factors that need to be addressed as well.

PMID- 28745421
TI  - Catalytic Reductive Pinacol-Type Rearrangement of Unactivated 1,2-Diols through a
      Concerted, Stereoinvertive Mechanism.
AB  - A catalytic pinacol-type reductive rearrangement reaction of internal 1,2-diols
      is reported herein. Several scaffolds not usually amenable to pinacol-type
      reactions, such as aliphatic secondary-secondary diols, undergo the
      transformation well without the need for prefunctionalization. The reaction uses
      a simple boron catalyst and two silanes and proceeds through a concerted,
      stereoinvertive mechanism that enables the preparation of highly enantiomerically
      enriched products. Computational studies have been used to rationalize the
      preference for migration over direct deoxygenation.

PMID- 28745422
TI  - Determination of different arsenic species in food-grade spirulina powder by ion
      chromatography combined with inductively coupled plasma mass spectrometry.
AB  - A "two-step" pressurized microwave-assisted extraction method coupled with ion
      chromatography with inductively coupled plasma mass spectrometry for the
      determination of different arsenic species in spirulina samples was developed.
      The extraction method used H2 O2 /H2 O (1:5, v/v) as solvent to extract all
      arsenic species except arsenite, which was extracted by using water as solvent.
      The extraction method had a satisfactory recovery (>96%) and took a short time
      (20.0 min). With our method, all arsenic species in spirulina samples were
      completely separated and determined with recoveries of 84-105% and relative
      standard deviations of 2-4%. Food-grade spirulina powder samples from seven
      provinces (Inner Mongolia, Zhejiang, Fujian, Hainan, Yunnan, Jiangsu, and
      Guangxi) in China were analyzed using the optimized protocol. Arsenate was
      detected at the concentration range of 170-394 ng/g in all the spirulina samples.
      Dimethylarsinic acid was detected at the concentration range of 32-839 ng/g in
      spirulina from above-six provinces except Guangxi. Monomethylarsonic acid (67 +/-
      3 ng/g) was detected only in spirulina from Yunnan province. Arsenite was
      detected at the concentration range of 28-147 ng/g in spirulina from above five
      provinces except Hainan and Guangxi. Five unknown organic arsenic species were
      found in spirulina from above six provinces except Guangxi.

PMID- 28745423
TI  - Effects of early life factors on the health and quality of life of older adults.
AB  - BACKGROUND: Few studies on the effects of early life factors on the health and
      quality of life of adults have been conducted in Turkey. We aimed to investigate
      the effects of early life factors on the health and quality of life of older
      adults. METHODS: We administered a questionnaire to 350 adults, aged 50-89 years,
      living in Cankaya, Ankara. The questionnaire covered sociodemographic
      characteristics, early life characteristics, health status, and the World Health
      Organization Quality of Life-Ageing scale. Data were analyzed using chi 2 tests,
      independent samples t-tests, one-way anova, and binary logistic regression
      analysis. RESULTS: The analyses showed that the most important risk factors for
      chronic disease were being >=65 years (odds ratio (OR) = 2.34), having a chronic
      health problem before 18 years of age (OR = 2.48), experiencing prolonged
      hospitalization or bed rest before 18 years of age (OR = 2.65), and experiencing
      parental unconcern during early life (OR = 2.13) (P < 0.05). In addition, having
      a high school education or less includes people who have primary or secondary or
      high school diploma (OR = 1.65), having lived in a village (OR = 1.65), having a
      low family economic status (OR = 2.40), and having experienced one negative event
      (OR = 1.41) or two or more negative events (OR = 1.39) during their early lives
      were identified as important risk factors for low quality of life (P < 0.05).
      CONCLUSION: Early life factors are among the important determinants of the health
      and quality of life of older adults in Turkey.

PMID- 28745424
TI  - Orthotopic liver transplantation in a pediatric patient with iatrogenic Budd
      Chiari syndrome complicated by bronchobiliary fistula.
AB  - We report a clinical case of OLT in a 10-year-old boy with iatrogenic BCS and BBF
      following three operations because of traumatic liver rupture and pulmonary
      contusion caused by a traffic accident 4 years ago. On follow-up, the child was
      asymptomatic.

PMID- 28745425
TI  - Experimental Realization of a High-Quality Biochemical XOR Gate.
AB  - We report an experimental realization of a biochemical XOR gate function that
      avoids many of the pitfalls of earlier realizations based on biocatalytic
      cascades. Inputs-represented by pairs of chemicals-cross-react to largely cancel
      out when both are nearly equal. The cross-reaction can be designed to also
      optimize gate functioning for noise handling. When not equal, the residual inputs
      are further processed to result in the output of the XOR type, by biocatalytic
      steps that allow for further gate-function optimization. The quality of the
      realized XOR gate is theoretically analyzed.

PMID- 28745426
TI  - Dual RNA-Seq of Lysobacter capsici AZ78 - Phytophthora infestans interaction
      shows the implementation of attack strategies by the bacterium and unsuccessful
      oomycete defense responses.
AB  - Biological interactions in the microbial communities of the rhizosphere
      continuously shape the gene expression patterns of each individual microorganism.
      A dual RNA-Seq approach was applied to obtain a comprehensive overview of the
      molecular mechanisms activated during the interaction between the biocontrol
      rhizobacterium Lysobacter capsici AZ78 and the soilborne phytopathogenic oomycete
      Phytophthora infestans. The RNA-Seq transcriptional profile of L. capsici AZ78
      was characterized by up-regulation of genes concerned in the biogenesis of type 4
      pilus and lytic enzymes, involved, respectively, in host colonization and
      subsequent attack of the P. infestans cell wall. The activation of detoxification
      processes allowed L. capsici AZ78 to overcome the attempted defense processes of
      P. infestans. Moreover, the genes involved in antibiotic biosynthesis were up
      regulated in L. capsici AZ78 and caused cell death in P. infestans, with the
      activation of putative apoptotic processes. The consequences of P. infestans cell
      death resulted in the down-regulation of primary metabolic pathways, such as
      carbohydrates, nucleic acids and protein metabolisms. Overall, the mechanism of
      action of L. capsici AZ78 was related to parasitism and predatory activities that
      cause the death of P. infestans.

PMID- 28745427
TI  - Relationship between work-family balance and job satisfaction among employees in
      China: A moderated mediation model.
AB  - Previous studies have revealed the association between work-family balance and
      job satisfaction. The present research further explored the underlying mechanism
      of this association and aimed to provide a moderated mediation model to explain
      if personality traits moderate the relationship between work-family balance and
      job satisfaction through work engagement. A cross-sectional study was conducted
      in which 263 employees from a petrochemical enterprise in China completed self
      report questionnaires including the Work-Family Balance Scale, the Utrecht Work
      Engagement Scale, the Big Five Inventory-10, and the Job Satisfaction Scale.
      Hierarchical regression analysis and structural equation modeling showed that
      work engagement partially mediated the relationship between work-family balance
      and job satisfaction, and the indirect effect was further moderated only by
      extraversion. Therefore, an integrative moderated mediation model was proposed
      wherein work-family balance boosts job satisfaction by first enhancing employees'
      work engagement, while the indirect effect was in turn moderated by extraversion.
      The results suggest that interventions for improving job satisfaction may be
      enhanced by targeting work engagement, especially for employees with higher
      extraversion.

PMID- 28745428
TI  - What Are We Missing? The Detergent Triton X-100 Added to Avoid Compound
      Aggregation Can Affect Assay Results in an Unpredictable Manner.
AB  - In this study we show that the detergent Triton X-100, which is widely used in
      screening campaigns, significantly decreases the binding affinities of some known
      specific inhibitors of HIV-1 protease and the well-established model protease
      endothiapepsin in a fluorescence-based assay. Surprisingly, other structurally
      related inhibitors remain entirely unaffected. As a consequence, those compounds
      that were affected would most likely have been misclassified as unspecific
      binders, although they are actually true positives, and thus could be considered
      excellent starting points for further hit optimization.

PMID- 28745429
TI  - Exploring the interior of cuticles and compressions of fossil plants by FIB-SEM
      milling and image microscopy.
AB  - We present the first study of cuticles and compressions of fossil leaves by
      Focused Ion Beam Scanning Electron Microscopy (FIB-SEM). Cavities preserved
      inside fossil leaf compressions corresponding to substomatal chambers have been
      observed for the first time and several new features were identified in the cross
      section cuts. These results open a new way in the investigation of the three
      dimensional structures of both micro- and nanostructural features of fossil
      plants. Moreover, the application of the FIB-SEM technique to both fossils and
      extant plant remains represent a new source of taxonomical, palaeoenvironmental
      and palaeoclimatic information.

PMID- 28745430
TI  - Supplementation of Nucleosides During Selection can Reduce Sequence Variant
      Levels in CHO Cells Using GS/MSX Selection System.
AB  - In the process of generating stable monoclonal antibody (mAb) producing cell
      lines, reagents such as methotrexate (MTX) or methionine sulfoximine (MSX) are
      often used. However, using such selection reagent(s) increases the possibility of
      having higher occurrence of sequence variants in the expressed antibody molecules
      due to the effects of MTX or MSX on de novo nucleotide synthesis. Since MSX
      inhibits glutamine synthase (GS) and results in both amino acid and nucleoside
      starvation, it is questioned whether supplementing nucleosides into the media
      could lower sequence variant levels without affecting titer. The results show
      that the supplementation of nucleosides to the media during MSX selection
      decreased genomic DNA mutagenesis rates in the selected cells, probably by
      reducing nucleotide mis-incorporation into the DNA. Furthermore, addition of
      nucleosides enhance clone recovery post selection and does not affect antibody
      expression. It is further observed that nucleoside supplements lowered DNA
      mutagenesis rates only at the initial stage of the clone selection and do not
      have any effect on DNA mutagenesis rates after stable cell lines are established.
      Therefore, the data suggests that addition of nucleosides during early stages of
      MSX selection can lower sequence variant levels without affecting titer or clone
      stability in antibody expression.

PMID- 28745431
TI  - Trabectedin is a promising antitumor agent potentially inducing melanocytic
      differentiation for clear cell sarcoma.
AB  - Clear cell sarcoma is an aggressive soft tissue sarcoma and highly resistant to
      conventional chemotherapy and radiation therapy. This devastating disease is
      defined by EWSR1-ATF1 fusion gene resulting from chromosomal translocation
      t(12;22)(q13;q12) and characterized by melanocytic differentiation. A marine
      derived antineoplastic agent, trabectedin, inhibits the growth of myxoid
      liposarcoma and Ewing sarcoma by causing adipogenic differentiation and neural
      differentiation, respectively. In this study, we examined the antitumor effects
      and mechanism of action of trabectedin on human clear cell sarcoma cell lines. We
      showed that trabectedin decreased the cell proliferation of five clear cell
      sarcoma cell lines in a dose-dependent manner in vitro and reduced tumor growth
      of two mouse xenograft models. Flow cytometry and immunoblot analyses in vitro
      and immunohistochemical analysis in vivo revealed that trabectedin-induced G2/M
      cell cycle arrest and apoptosis. Furthermore, trabectedin increased the
      expression of melanocytic differentiation markers along with downregulation of
      ERK activity in vitro and the rate of melanin-positive cells in vivo. These
      results suggest that trabectedin has potent antitumor activity against clear cell
      sarcoma cells by inducing cell cycle arrest, apoptosis, and, in part, by
      promoting melanocytic differentiation through inactivation of ERK signaling. Our
      present study indicates that trabectedin is a promising differentiation-inducing
      agent for clear cell sarcoma.

PMID- 28745432
TI  - An Ectosteric Inhibitor of Cathepsin K Inhibits Bone Resorption in Ovariectomized
      Mice.
AB  - The potent cathepsin K (CatK) inhibitor, Tanshinone IIA sulfonic sodium (T06),
      was tested for its in vitro and in vivo antiresorptive activities. T06 binds in
      an ectosteric site of CatK remote from its active site and selectively inhibits
      collagen degradation with an IC50 value of 2.7 +/- 0.2 MUM (CatK:T06 molar ratio
      of 1:5). However, it does not suppress fluorogenic peptide cleavage and
      gelatinolysis at a 2500-fold molar excess. Contrary to active site-directed CatK
      inhibitors, such as odanacatib, T06 suppresses bone resorption in both human and
      mouse osteoclasts equally well (IC50 value for human and mouse osteoclasts: 237
      +/- 60 nM and 245 +/- 55 nM, respectively) and its antiresorptive activity is
      fully reversible in both cell types. Moreover, T06 affects neither the metabolic
      activity of osteoclasts nor osteoclastogenesis. In in vivo studies, 40 mg
      T06/kg/d given to 12-week-old ovariectomized (OVX) mice for 3 months reduced
      plasma CTx-1 by 20% and increased osteoblast numbers and plasma P1NP by ~28% when
      compared with the OVX control. MUCT analysis of T06-treated OVX mice showed a 35%
      increase in bone mineral density and other femoral trabecular bone parameters
      when compared with OVX animals. T06 did not alter the number of osteoclasts, had
      no estrogenic effect on the uterus, did not change plasma estradiol levels, and
      did not inhibit fibroblast-mediated TGF-beta1 processing or degradation and
      cognitive functions in OVX mice. This study indicates that the ectosteric
      inhibitor, T06, is a selective antiresorptive CatK inhibitor that may overcome
      the shortcomings of side effect-prone active site-directed drugs, which all
      failed in clinical trials. (c) 2017 American Society for Bone and Mineral
      Research.

PMID- 28745433
TI  - Transcriptome analysis in primary colorectal cancer tissues from patients with
      and without liver metastases using next-generation sequencing.
AB  - Colorectal cancer (CRC) is the third most common cancer worldwide and liver
      metastases are the leading cause of death in patients with CRC. In this study, we
      performed next-generation sequencing profiling on primary colorectal tumor
      tissues obtained from three CRC patients with liver metastases and three CRC
      patients without liver metastases to identify differentially expressed genes
      (DEGs) that might be responsible for the metastases process. After filtering 2690
      DEGs, comprising 996 upregulated and 1694 downregulated RNAs, 22 upregulated and
      73 downregulated DEGs were identified. Gene ontology (GO) and pathway analyses
      were performed to determine the underlying mechanisms. Single-organism process
      (biological process), cell (cellular component), and binding (molecular function)
      were the most related terms in the GO analysis. We selected the top 13
      upregulated and top 12 downregulated genes by fold change to verify their
      differential expression using quantitative real-time reverse transcription PCR
      (qRT-PCR) and immunohistochemistry (IHC). The validation showed that three most
      significantly upregulated DEGs were HOXD10, UGT2A3, and SLC13A2, whereas the five
      most significantly downregulated DEGs were SPP1, CXCL8, MMP3, OSM, and CXCL6,
      respectively. These aberrantly expressed genes may play pivotal roles in
      promoting or inhibiting metastases. Further studies are required to determine the
      functions of DEGs to promote the diagnosis of metastases and provide novel
      chemotherapy targets.

PMID- 28745434
TI  - Dark personality profiles: Estimating the cluster structure of the Dark Triad.
AB  - We estimated the number of possible dark personality profiles in a large
      population (N = 18,088) using a subtractive clustering method, which suggested
      three cluster or dark personality profiles: high malevolent, intermediate
      malevolent, and low malevolent or benevolent. While the three profiles differed
      significantly in each dark trait, there was a considerably large cluster overlap.

PMID- 28745435
TI  - MAPK-15 is a ciliary protein required for PKD-2 localization and male mating
      behavior in Caenorhabditis elegans.
AB  - Cilia are conserved cellular structures that facilitate sensory-based processes,
      including those required for neuronal and kidney functions. Here, we show that
      the human mitogen activated kinase-15 (MAPK-15) ortholog in Caenorhabditis
      elegans encodes a ciliary protein. A strain harboring a mutation in the catalytic
      site of the kinase domain results in ciliary-specific defects in tail neurons of
      both hermaphrodite and male worms, manifesting in dye uptake, dendrite extension,
      and male mating behavior defects. Transgenic-fusion constructs for two mapk-15
      isoforms (A and C) with full-length kinase domains were generated. Expression of
      either the A- or C-specific isoform rescues the dye-filling and male-mating
      defective phenotypes, confirming the ciliary function of mapk-15. Expression of
      mapk-15 occurs in many ciliated-sensory neurons of the head and tail in
      hermaphrodite and male worms. Localization of MAPK-15 isoforms A and C occurs in
      the cell body, dendritic processes, and cilia. A C. elegans ortholog of
      polycystin-2, a protein that when defective in mammals results in autosomal
      dominant polycystic kidney disease, is mislocalized in the male ray neurons of
      mapk-15 mutant worms. Expression of the mapk-15 gene by the pkd-2 promoter
      partially rescues the male-mating defects observed in mapk-15 mutant animals.
      Expression of mapk-15 is DAF-19/RFX dependent in some CSNs and DAF-19/RFX
      independent in others. Collectively, these data suggest that MAPK-15 functions
      upstream of PKD-2 localization to modulate ciliary sensory functions.

PMID- 28745436
TI  - Comparison of four different fuller's earth formulations in skin decontamination.
AB  - Industrial accidents, wars and terrorist threats are potential sources of skin
      contamination by highly toxic chemical warfare agents and manufacturing
      compounds. We have compared the time-dependent adsorption capacity and
      decontamination efficiency of fuller's earth (FE) for four different formulations
      for the molecular tracer, 4-cyanophenol (4-CP), in vitro and ex vivo using water
      decontamination as standard. The adsorption capacity of FE was assessed in vitro
      for 4-CP aqueous solutions whereas decontamination efficiency was investigated ex
      vivo by tracking porcine skin 4-CP content using attenuated total reflectance
      Fourier transform infrared spectroscopy. Decontamination was performed on short
      time, exposed porcine skin to 4-CP by application of FE: (1) as free powder; (2)
      loaded on adhesive tape; (3) on powdered glove; or (4) in suspension. Removal
      rate of 4-CP from aqueous solutions correlates with the amount of FE and its
      contact time. Decontamination efficiency estimated by the percentage of 4-CP
      recovery from contaminated porcine skin, achieved 54% with water, ranged between
      ~60 and 70% with dry FE and reached ~90% with FE suspension. Successful
      decontamination of the FE suspension, enabling a dramatic reduction of skin
      contamination after a brief exposure scenario, appears to be rapid, reliable and
      should be formulated in a new device ready to use for self-application.

PMID- 28745437
TI  - Vascularized ulnar periosteal pedicled flap for forearm reconstruction:
      Anatomical study and a case report.
AB  - PURPOSE: Through an anatomical review, the aim of this study is to define the
      ulnar periosteal branches of the posterior interosseous vessels (PIV). In
      addition, we report the clinical utility of a vascularized ulnar periosteal
      pedicled flap (VUPPF), supplied by the investigated PIV, in a complex case of
      radial nonunion. METHODS: Ten upper limbs latex colored from fresh human cadavers
      were used. Branches of the PIV were dissected under 2.5* loupe magnification,
      noting the periosteal, muscular, and cutaneous branches arising distal to the
      interosseous recurrent artery. The VUPPF was measured in length (cm) and width
      (cm). RESULTS: The PIV provided a mean 12.8 periosteal branches to the ulna
      distributed along the most distal 15 cm, with a mean distance between branches of
      1 cm, allowing for the design of a VUPPF which measured a mean 12 cm in length
      and 1.7 cm in width. We used a VUPPF of 7.8 cm in length and 2 cm in width to
      treat extensive nonvascularized bone graft nonunion with a defect of 2 cm of the
      left radius in a 6-year-old girl, secondary to previous Ewing's Sarcoma
      reconstruction. Successfully consolidation was achieved 6-months after surgery.
      The patient did not present postoperative complications. At 2-years of follow-up
      after surgery, active supination was 80 degrees  and pronation 0 degrees  (due an
      incomplete interosseous ossification); grip strength was 80% that of the opposite
      hand. The patient had resumed all her daily activities. CONCLUSIONS: VUPPF may be
      considered a valuable and reliable surgical option for forearm reconstruction in
      complex clinical scenarios.

PMID- 28745438
TI  - Functional donor site morbidity longer than one year after fibula free flap: A
      prospective biomechanical analysis.
AB  - OBJECTIVES: The fibula free flap is the workhorse procedure for osseous
      reconstruction. The objective of this study was to investigate long-term
      functional outcomes of the harvesting site. PATIENTS AND METHODS: About 19
      patients (10 male, 9 female, mean age 58.1 years) were available for the long
      term analysis 13-51 months after surgery. Jumping mechanography and balance
      testing on a ground force reaction plate (Leonardo Mechanograph GFRP) were
      performed before and surgery. The Esslinger Fitness Index (EFI, maximum peak
      power in W/kg normalized for age and gender) was considered as primary endpoint.
      Secondary outcomes were maximum force, range of motion in the ankle joint,
      sensory limitations, the American Orthopedic Foot and Ankle Society Score (AOFAS
      Score), and subjective perceptions. RESULTS: We found no significant difference
      between pre- and postoperative EFI (70.4% versus 66.0%, P = 0.07) and body sway
      (1.72 cm2 versus 2.60 cm2 , P = 0.093). The AOFAS-Score was reduced by 8.8 points
      (99.1 points versus 90.3 points, P < 0.001). Dorsal extenstion (31.6 degrees 
      versus 24.1 degrees , P < 0.001) and flexion (32.3 versus 25.6 degrees  flexion,
      P = 0.011) were significantly reduced and 6 patients had chronic pain.
      CONCLUSIONS: Reduced peak power and balance ability seem to be reversible short
      term effects after fibula harvesting. We recommend preoperative patient education
      and standardized protocols for physiotherapy.

PMID- 28745439
TI  - A Double-Stimuli-Responsive Fluorescent Center for Monitoring of Food Spoilage
      based on Dye Covalently Modified EuMOFs: From Sensory Hydrogels to Logic Devices.
AB  - Unsafe food is a huge threat to human health and the economy, and detecting food
      spoilage early is an ongoing and imperative need. Herein, a simple and effective
      strategy combining a fluorescence sensor and one-to-two logic operation is
      designed for monitoring biogenic amines, indicators of food spoilage. Sensors
      (methyl red@lanthanide metal-organic frameworks (MR@EuMOFs)) are created by
      covalently modifying MR into ?NH2 -rich EuMOFs, which have a high quantum yield
      (48%). A double-stimuli-responsive fluorescence center is produced via energy
      transfer from the ligands to Eu3+ and MR. Portable sensory hydrogels are obtained
      by dispersing and solidifying MR@EuMOFs in water-phase sodium salt of carboxy
      methyl cellulose (CMC-Na). The hydrogels exhibit a color transition upon
      "smelling" histamine (HI) vapor. This transition and shift in the MR-based
      emission peak are closely related to the HI concentration. Using the HI
      concentration as the input signal and the two fluorescence emissions as output
      signals, an advanced analytical device based on a one-to-two logic gate is
      constructed. The four output combinations, NOT (0, 1), YES (1, 0), PASS 1 (1, 1),
      and PASS 0 (0, 0), allow the direct analysis of HI levels, which can be used for
      real-time food-freshness evaluation. The novel strategy suggested here may be a
      new application for a molecular logic system in the sensing field.

PMID- 28745440
TI  - Design Rules for Oxygen Evolution Catalysis at Porous Iron Oxide Electrodes: A
      1000-Fold Current Density Increase.
AB  - Nanotubular iron(III) oxide electrodes are optimized for catalytic efficiency in
      the water oxidation reaction at neutral pH. The nanostructured electrodes are
      prepared from anodic alumina templates, which are coated with Fe2 O3 by atomic
      layer deposition. Scanning helium ion microscopy, X-ray diffraction, and Raman
      spectroscopy are used to characterize the morphologies and phases of samples
      submitted to various treatments. These methods demonstrate the contrasting
      effects of thermal annealing and electrochemical treatment. The electrochemical
      performances of the corresponding electrodes under dark conditions are quantified
      by steady-state electrolysis and electrochemical impedance spectroscopy. A rough
      and amorphous Fe2 O3 with phosphate incorporation is critical for the
      optimization of the water oxidation reaction. For the ideal pore length of 17
      MUm, the maximum catalytic turnover is reached with an effective current density
      of 140 MUA cm-2 at an applied overpotential of 0.49 V.

PMID- 28745441
TI  - Clinical staff nurse leadership: Identifying gaps in competency development.
AB  - BACKGROUND: To date, there has been no development of a complete, applicable
      inventory of clinical staff nurse (CSN) leadership role competencies through a
      valid and reliable methodology. Further, the CSN has not been invited to engage
      in the identification, definition, or development of their own leadership
      competencies. OBJECTIVE: Compare existing leadership competencies to identify and
      highlight gaps in clinical staff nurse leadership role competency development and
      validation. METHOD: Literature review. RESULTS: The CSN has not participated in
      the development of CSN leadership role competencies, nor have the currently
      identified CSN leadership role competencies been scientifically validated through
      research. Finally, CSN leadership role competencies are incomplete and do not
      reflect the CSN perspective.

PMID- 28745442
TI  - Modification of pedicle lengthening through perforator transposition in free
      anterolateral thigh flaps with pedicle size discrepancy: A case report.
AB  - In spite of thorough presurgical planning, emergency situations requiring longer
      pedicle length may arise during anterolateral thigh (ALT) free flap surgeries.
      While performing vessel graft for pedicle lengthening, discrepancy may occur
      because of a certain genetic predisposition or vascular variation at the
      anastomosis site of the graft vessel and the flap pedicle. A 76-year-old male
      patient with neurofibromatosis type I had a 15 x 10 cm defect, which was caused
      by radical excision of a malignant peripheral nerve sheath tumor on his back. A
      15 x 10 cm sized free ALT flap was obtained. The distance between the recipient
      vessels and the defect area was 20 cm. The diameters of vessels in the harvested
      flap were as follows: proximal end of the descending branch of the lateral
      circumflex femoral artery (LCFA)-artery/vein: 3.0/2.5 mm, distal end of the
      descending branch of the LCFA-artery/vein: 1.0/1.0 mm, and perforator in the ALT
      flap-artery/vein: 0.8/1.0 mm. The conventional method requires transfer of the
      distal portion of the LCFA (below the bifurcation) which mandates us to perform
      anastomoses with a vessel diameter discrepancy of 2 mm. As an alternative, a
      bifurcating perforator-including flap was transposed to the most distal part of
      the descending branch of the LCFA. An ALT flap with a pedicle having a total
      length of 20 cm was constructed. The flap survived without any complications.
      This technique may provide an option for resolving size discrepancy between the
      graft vessel and the ALT pedicle.

PMID- 28745443
TI  - Discrimination between patients with mild Alzheimer's disease and healthy
      subjects based on cerebral blood flow images of the lateral views in xenon
      enhanced computed tomography.
AB  - BACKGROUND: Quantitative cerebral blood flow (CBF) measurement is expected to
      help early detection of functional abnormalities caused by Alzheimer's disease
      (AD) and enable AD treatment to begin in its early stages. Recently, a technique
      of layer analysis was reported that allowed CBF to be analyzed from the outer to
      inner layers of the brain. The aim of this work was to develop methods for
      discriminating between patients with mild AD and healthy subjects based on CBF
      images of the lateral views created with the layer analysis technique in xenon
      enhanced computed tomography. METHODS: Xenon-enhanced computed tomography using a
      wide-volume CT was performed on 17 patients with mild AD aged 75 or older and on
      15 healthy age-matched volunteers. For each subject, we created CBF images of the
      right and left lateral views with a depth of 10-15 mm from the surface of the
      brain. Ten circular regions of interest (ROI) were placed on each image, and CBF
      was calculated for each ROI. We determined discriminant ROI that had CBF that
      could be used to differentiate between the AD and volunteer groups. AD patients'
      CBF range (mean - SD to mean + SD) and healthy volunteers' CBF range (mean - SD
      to mean + SD) were obtained for each ROI. Receiver-operator curves were created
      to identify patients with AD for each of the discriminant ROI and for the AD
      patients' and healthy volunteers' CBF ranges. RESULTS: We selected an ROI on both
      the right and left temporal lobes as the discriminant ROI. Areas under the
      receiver-operator curve were 93.3% using the ROI on the right temporal lobe,
      95.3% using the ROI on the left temporal lobe, and 92.4% using the AD patients'
      and healthy volunteers' CBF ranges. CONCLUSIONS: We could effectively
      discriminate between patients with mild AD and healthy subjects using ROI placed
      on CBF images of the lateral views in xenon-enhanced computed tomography.

PMID- 28745444
TI  - Comparison of the proteomes of mouse Skin Derived Precursors (SKPs) and SKP
      derived fibroblasts (SFBs) by iTRAQ.
AB  - Skin-derived precursors (SKPs) can differentiate into fibroblasts. However,
      little is known about the molecular mechanism of the differentiation process. Our
      previous study has compared the transcriptomes of mouse SKPs and SKP-derived
      fibroblasts (SFBs) by RNA-Seq analysis and found some genes and signal pathways
      that might play important roles in the transition from SKPs to SFBs. Here, to
      further investigate the process by which SKPs differentiate into fibroblasts, we
      compared the proteomes between SKPs and SFBs using iTRAQ. Our results showed that
      243 differentially expressed proteins (DEPs) were identified. Among the 28 DEPs
      which were related to the functional group of cell differentiation, Down
      regulated DEPs collagen XVIII, keratin 10, keratin 5, keratin 14, and TIFIbeta,
      up-regulated DEPs Thy-1, ANXA1, alpha-catenin, and calreticulin might play
      important roles in the transition of SKPs to fibroblasts. Further study is needed
      to clarify the roles of these proteins in the differentiation process of SKPs
      into fibroblasts, which could facilitate investigations of the detailed molecular
      mechanisms in the process and make it possible to take advantage of the potential
      therapeutic applications of SKPs in skin regeneration in the future.

PMID- 28745445
TI  - Switchable Stereoselectivity in Bromoaminocyclization of Olefins: Using Bronsted
      Acids of Anionic Chiral Cobalt(III) Complexes.
AB  - Bronsted acids of anionic chiral CoIII complexes act as bifunctional phase
      transfer catalysts to shuttle the substrates across the solvent interface and
      control stereoselectivity. The diastereomeric chiral CoIII -templated Bronsted
      acids, with the same chiral ligands, enabled a switch in the enantioselective
      bromoaminocyclization of olefins to afford the two enantiomers of 2-substituted
      pyrrolidines with high enantioselectivities (up to 99:1 e.r.).

PMID- 28745446
TI  - Conclusion: Special issue on genetic and alcohol use disorder research with
      diverse racial/ethnic groups: Key findings and potential next steps.
AB  - BACKGROUND AND OBJECTIVES: This special issue brings together papers focusing on
      a wide range of topics relevant to the research and understanding of the role of
      race/ethnicity and genetic variation for the susceptibility of developing an
      alcohol use disorder (AUD). METHODS: The key findings from the issue's 10
      articles are reviewed and organized here around three topics: I: addictive
      behaviors and potential environmental influences; II: a focus on four
      racial/ethnic groups; and III: special methodologies. RESULTS: Several potential
      next steps in improving effective research strategies are highlighted: (1)
      implementing best practices for outreach and community engagement may reduce
      reluctance to participate; (2) recruiting adequately sized and
      racially/ethnically diverse samples will require new collaborations with
      investigators who successfully work in diverse communities; (3) identifying and
      assessing environmental influences that are both unique to, and common among,
      racial/ethnic groups may inform preventions for AUD; (4) use of standardized
      measures will facilitate the generation of larger samples and meta-analysis of
      research findings; and (5) use of better analytic approaches and experimental
      methods will improve replication in gene finding research and help advance new
      areas of research. CONCLUSIONS: Genetic research of AUD in diverse racial/ethnic
      populations is advancing. The articles in this issue examined the general theme
      of including diverse population groups in genetic studies and offered potential
      strategies for addressing some common problems. SCIENTIFIC SIGNIFICANCE: Greater
      inclusion of diverse racial/ethnic populations in this research is important to
      ensure that the benefits of new knowledge and technology are equally shared. (Am
      J Addict 2017;26:532-537).

PMID- 28745448
TI  - Issue Information - ToC.

PMID- 28745447
TI  - Commentary: Perspectives on alcohol-related gene and environment interplay in
      diverse populations.
AB  - BACKGROUND AND OBJECTIVES: Racial/ethnic groups comprise more than 20% of the
      U.S. population, but many experience disproportionately high risk for alcohol
      misuse, often resulting in higher rates of alcohol-associated consequences.
      Completion of mapping the human genome has launched rapidly evolving research
      methods aimed at improved understanding of genetic contribution to disease.
      Despite decades of research on the influence of genetic and environmental risks
      on alcohol use disorders and outcomes, few studies have included racial/ethnic
      subpopulations in sufficient numbers to allow for proper statistical analysis.
      METHODS: The papers in this special issue help to elucidate current knowledge on
      the etiology of genetic and environmental contributors and potential moderators
      of alcohol use and associated problems among racial/ethnic populations. The lack
      of racial/ethnic diversity across many genetic studies contributes to challenges
      in interpretation of findings and eventually applications to precision medicine.
      RESULTS: Proposed approaches to overcome disparities in racial/ethnic participant
      recruitment in genetic studies include methods to address population
      stratification in allele frequency, improve transparency in subjects' consenting
      to participate, and engaging interdisciplinary research teams and community
      involvement to improve recruitment of racial/ethnic minorities. DISCUSSION AND
      CONCLUSIONS: The reviews presented underscore various gaps in our knowledge of
      the genetic influences on alcohol use disorders due to the failure to include
      racially and ethnically diverse populations in genetic and epigenetic study
      samples. New directions are suggested to overcome the resulting research
      challenges and ultimately to inform future personalized intervention approaches
      for racial/ethnic populations. SCIENTIFIC SIGNIFICANCE: Inclusion of
      heterogeneous populations in genomic research will provide a better comprehension
      of possible unique genetic factors in the broader general population that may be
      missed due to exclusion of unique and common variants that may be present in
      racial/ethnic populations. (Am J Addict 2017;26:526-531).

PMID- 28745449
TI  - Special Issue on Diversity, Alcohol, and Genetics.

PMID- 28745450
TI  - Issue Information - Editorial Board.

PMID- 28745451
TI  - Analysis of Reaction Processes On the Basis of the Evolution of Dynamic Orbital
      Forces: Examples of Cycloadditions, SN 2 Substitution, Nucleophilic Addition, and
      Hydrogen Transposition.
AB  - The derivative of the energy of a canonical molecular orbital (MO) [or dynamical
      orbital forces (DOFs)] with respect to a bond length provides a reliable index of
      the bonding/antibonding character of this MO on this bond. The DOFs of selected
      MOs as a function of the reaction coordinate were computed for a panel of model
      reaction mechanisms: [2+4] (Diels-Alder) cycloaddition, [2+2] cycloaddition,
      second-order nucleophilic substitution (SN 2), nucleophilic addition to a
      carbonyl group, and [1,2] hydrogen transposition. The results highlight the
      nature of the reorganization of the main MOs and the stage of the reaction
      coordinate (RC) at which it occurs. For instance, in the Diels-Alder reaction,
      one can identify a part of the reaction that is dominated by repulsive four
      electron interactions and another part dominated by attractive two-electron
      interactions. Also, the shape of the DOF as a function of the reaction coordinate
      reveals the existence of avoided MO crossings and their location on the RC. Even
      for spontaneous reactions with monotonic variation in the potential energy,
      extrema of the MO energy and sudden electron rearrangements can be put into
      evidence. This study provides quantitative support to classical MO analyses of
      reactivity such as correlation diagrams and frontier approximation.

PMID- 28745452
TI  - Recent Progress in Application of Graphene Supported Metal Nanoparticles in C-C
      and C-X Coupling Reactions.
AB  - The carbon-carbon and carbon-heteroatom bonds catalytic formation is among the
      most significant reactions in organic synthesis which extensively applied for
      synthesis of natural products, heterocycles, dendrimers, biologically active
      molecules and useful compounds. This review provides the latest advances in the
      preparation of graphene supported metal nanoparticles and their application in
      the catalytic formation of both carbon-carbon (C-C) and carbon-heteroatom (C-X)
      bonds including the Suzuki, Heck, Hiyama, Ullmann, Buchwald and Sonogashira
      coupling reactions. Numerous examples are given concerning the use of these
      catalysts in C-C and C-X coupling reactions along with the reliable and simple
      preparation methods of these catalysts, their characterization and catalytic
      properties and also the recycling possibilities.

PMID- 28745453
TI  - Conscious awareness and time perception.
AB  - This paper examines Zhou, Poppel, and Bao's 2014 proposal ("In the Jungle of
      Time: The Concept of Identity as a Way Out,"
      https://doi.org/10.3389/fpsyg.2014.00844) to unify the psychology of time through
      a biological principle concerning identity and homeostasis. Although the present
      analysis largely agrees with their proposal, it argues that a Dual Model of time
      (see Montemayor's 2013 monograph, Minding Time: A Philosophical and Theoretical
      Approach to the Psychology of Time) is needed to account for two important roles
      in time cognition, one related to navigation and the other to conscious
      awareness. In a Dual Model, the homeostatic principle plays a critical role with
      respect to conscious awareness, but a different principle is needed for
      integrating the metric constraints on navigation.

PMID- 28745454
TI  - Metal-based antimicrobial strategies.
AB  - Metal based-antimicrobials have potential for profiling sustainability solutions
      to infection care and health; with biotechnological applications providing novel
      compounds. Yet they must be used wisely for sustainable use in human and
      agricultural health with thoughts towards bioremediation for recovery should be
      considered.

PMID- 28745455
TI  - Identification and characterization of a gene involved in the encapsulation
      response of Helicoverpa armigera haemocytes.
AB  - Encapsulation is a kind of cellular immune response of insect haemocytes, which
      results in the formation of capsules around invading parasites. However, the
      molecular mechanism of this response is largely unknown. In this study, we
      identified a potential immune-related gene in the cotton bollworm, Helicoverpa
      armigera, called defence protein 1 (Ha-DFP1). A tissue distribution analysis
      revealed that Ha-DFP1 protein was expressed in haemocytes and secreted into the
      haemolymph of Helic. armigera larvae. The Ha-DFP1 mRNA transcript level in
      haemocytes and the concentration of the Ha-DFP1 protein in haemolymph both
      increased after injecting chromatography beads. Purified recombinant Ha-DFP1
      bound to the surface of haemocytes and promoted haemocyte encapsulation on
      chromatography beads in vitro. The spreading ability of haemocytes was inhibited
      when Ha-DFP1 expression in Helic. armigera larval haemocytes decreased in
      response to the injection of double-stranded RNA specific to Ha-DFP1, and the
      encapsulation ability of haemocytes was impaired. Based on these results, we
      speculate that Ha-DFP1 plays an important role in the Helic. armigera
      encapsulation response, possibly by binding to the haemocyte surface and
      mediating spreading behaviour.

PMID- 28745456
TI  - Pediatric T-ALL complicated by irreversible nelarabine neurotoxicity.

PMID- 28745457
TI  - Discrimination of Diamond-Blackfan anemia from parvovirus B19 infection by RBC
      glutathione.

PMID- 28745458
TI  - Novel PRKAR1A mutation in Carney complex with cardiac myxoma.

PMID- 28745459
TI  - Swimming attendance during childhood and development of asthma: Meta-analysis.

PMID- 28745460
TI  - Lobar occlusion of pulmonary arteriovenous malformations with Amplatzer vascular
      plug.

PMID- 28745461
TI  - Neonatal perforated appendicitis in incarcerated inguinal hernia in the
      differential diagnosis of testis torsion.
AB  - Appendicitis in newborns is uncommon and difficult to diagnose. Reports on
      neonatal appendicitis subsequent to inguinal hernia incarceration are
      exceptionally rare. We present the case of a 26-day-old infant with perforated
      appendicitis due to incarceration of a right inguinal hernia, mimicking right
      testicular torsion.

PMID- 28745462
TI  - Swimming pool attendance during childhood and development of asthma: Reply.

PMID- 28745463
TI  - Synthetic microbiology: from analogy to methodology.

PMID- 28745464
TI  - Elite athletes and pubertal delay.
AB  - Intensive physical training and participation in competitive sports during
      childhood and early adolescence may affect athletes' pubertal development. On the
      other hand, pubertal timing, early or late, may impact on an athlete selection
      for a particular sport. Genetic predisposition, training load, nutritional status
      and psychological stress determine athletes' pubertal timing. Athletes that
      practice esthetic sports, especially gymnasts, are predisposed to a delay in
      pubertal development. The growing evidence indicates that energy deficiency, not
      a systemic training per se, plays a crucial role in the pathogenesis of
      functional hypothalamic hypogonadism in female athletes. Metabolic and
      psychologic stress activate hypothalamic-pituitary-adrenal axis and suppress
      hypothalamic-pituitary-ovarian axis. Female athletes who do not begin secondary
      sexual development by the age of 14 or menstruation by the age of 16 warrant a
      comprehensive evaluation and a targeted treatment. Somatic growth and sexual
      maturation of elite female athletes are largely sport-specific since each sport
      favors a particular somatotype and requires a specific training. Chronic negative
      energy balance resulting from a systemic physical training and inadequate energy
      intake may delay pubertal development in elite athletes. Youth athletes,
      especially those engaged in competitive sports that emphasize prepubertal or lean
      appearance, are at risk of developing relative energy deficiency in sport
      associated with disordered eating or eating disorders. Management strategies
      should address the complex conditions underlying functional hypothalamic
      hypogonadism.

PMID- 28745465
TI  - Premature ventricular complexes in children with structurally normal hearts:
      clinical review and recommendations for diagnosis and treatment.
AB  - Premature ventricular complexes (PVCs) have always been a matter of debate among
      physicians and a cause for concern for family members of affected patients. The
      available literature on isolated PVCs in children is limited to case reports and
      small single-center retrospective series that are consistent in demonstrating the
      benign course of PVCs and their frequent disappearance during childhood, though
      many questions remain unanswered. Nevertheless, two key actions should be
      undertaken in pediatric patients with documented PVCs: 1) to rule out the
      presence of structural heart disease; 2) to determine whether symptoms are due to
      PVCs, or whether PVC frequency is responsible for left ventricular dysfunction.
      This document aims to provide concise and easy to understand recommendations on
      the diagnostic work-up of healthy children with simple PVCs and the appropriate
      clinical and therapeutic approach.

PMID- 28745466
TI  - Dilated cardiomyopathy in celiac disease: what is the plot of the story?

PMID- 28745467
TI  - Ictal and interictal electroencephalogram of benign infantile seizures associated
      with mild gastroenteritis.

PMID- 28745468
TI  - Short stature and high serum transaminase levels: growth hormone deficiency in a
      child with Becker muscular dystrophy.

PMID- 28745469
TI  - Reliability of bounce drop jump parameters within elite male rugby players.
AB  - BACKGROUND: The aims of the study were to investigate the number of
      familiarization sessions required to establish reliability of the bounce drop
      jump (BDJ) and subsequent reliability once familiarization is achieved. METHODS:
      Seventeen trained male athletes completed 4 BDJs in 4 separate testing sessions.
      Force-time data from a 20 cm BDJ was obtained using two force plates (ensuring
      ground contact <250 ms). Subjects were instructed to "jump for maximal height and
      minimal contact time" while the best and average of four jumps were compared. A
      series of performance variables were assessed in both eccentric and concentric
      phases including jump height, contact time, flight time, Reactive Strength Index
      (RSI), peak power, rate of force development (RFD) and actual dropping height
      (ADH). Reliability was assessed using the intraclass correlation coefficient
      (ICC) and coefficient of variation (CV) while familiarization was assessed using
      a repeated-measures analysis of variance (ANOVA). RESULTS: The majority of DJ
      parameters exhibited excellent reliability with no systematic bias evident, while
      the average of 4 trials provided greater reliability. With the exception of
      vertical stiffness (CV: 12.0%) and RFD (CV: 16.2%), all variables demonstrated
      low within subject variation (CV range: 3.1-8.9%). Relative reliability was very
      poor for ADH, with heights ranging from 14.87-29.85 cm. CONCLUSIONS: High levels
      of reliability can be obtained from the BDJ with the exception of vertical
      stiffness and RFD, however, extreme caution must be taken when comparing DJ
      results between individuals and squads due to large discrepancies between actual
      drop height and platform height.

PMID- 28745470
TI  - Effects of taurine on markers of muscle damage, inflammatory response and
      physical performance in triathletes.
AB  - BACKGROUND: The practice of prolonged exercise with high intensity, as seen in
      triathlon training, can cause physiological imbalances that might result in
      muscle fatigue, muscle damage and changes in systemic inflammatory response, thus
      reduce the athletes' physical performance, therefore, both adequate total caloric
      and macronutrient intake also the use of a specific ergogenic aid, as taurine
      supplementation would be an alternative to prevent inflammation and muscle
      damage. In order to verify the effects of 8 weeks of taurine and chocolate milk
      supplementation, markers of muscle damage, inflammation, and aerobic capacity
      were quantified in triathletes. METHODS: A double-blind, crossover, randomized
      study was conducted with 9 male long-distance triathletes, aged 25-35 years.
      Supplementation of 3 g of taurine (TAU) or placebo (PLA) associated with 400 mL
      low fat chocolate milk was performed during an 8-week period. In order to verify
      the effects of the supplementation protocol markers of muscle damage as lactate
      dehydrogenase (LDH) and creatine kinase (CK), and inflammatory markers tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were quantified, also
      triathletes' performance was evaluated by exhaust test on a treadmill. RESULTS:
      It was observed a significant increase in taurine and CK plasma levels after TAU
      supplementation (P=0.02 and P=0.01, respectively). However, LDH concentrations
      did not differ significantly after the supplementations performed, and there were
      no changes in physical performance parameters; anaerobic threshold, perceived
      exertion, heart rate, and the concentrations of IL-6 and TNF-alpha. CONCLUSIONS:
      Taurine supplementation did not provide benefits on performance and muscle damage
      in triathletes.

PMID- 28745471
TI  - Visual control in basketball shooting under exertion conditions.
AB  - BACKGROUND: This study examined the effect of physical exertion on gaze behavior
      during basketball shooting in both stationary and dynamic conditions. METHODS:
      Thirteen skilled basketball players performed two-point shooting during a 60
      second fatigue protocol. Before and after a jump shot test, players performed two
      free throws. Eye movements were registered using an SMI Mobile EyeTracker. The
      frequency of all fixation points (number) and fixation duration during the motor
      phases of shooting were determined using frame-by-frame analysis. RESULTS: The
      type of basketball shot differentiated gaze control: 1) fixations were longer and
      more frequent during free throws as compared to jump shots; 2) shooting accuracy
      was positively influenced by less frequent and longer fixations; 3) physical
      exertion resulted in significantly more frequent fixations during free throws;
      and 4) exertion conditions resulted in a high variation in the patterns of total
      fixation times during jump shots. CONCLUSIONS: The findings suggest that physical
      exertion may reduce oculomotor efficiency during aiming at a distant target.
      Moreover, stationary and dynamic shots require different gaze behavior
      strategies.

PMID- 28745472
TI  - Effect of eight weeks of upper-body plyometric training during the competitive
      season on professional female volleyball players.
AB  - BACKGROUND: The purpose of this study was to assess the effect of incorporating
      specific upper-body plyometric training for the spike into the competitive season
      of a women's professional volleyball team. METHODS: A professional team from the
      Spanish first division participated in the study. An A-B-A' quasi-experimental
      design with experimental and control groups was used. The independent variable
      was the upper-body plyometric training for eight weeks during the competitive
      season. The dependent variables were the spiked ball's speed (km/h); the player's
      body weight (kg), BMI (kg/m2), and muscle percentage in arms (%); 1 repetition
      maximum (1RM) in the bench press (kg); 1RM in the pullover (kg); and overhead
      medicine ball throws of 1, 2, 3, 4, and 5 kg (m). Inter-player and inter-group
      statistical analyses of the results were carried out (Wilcoxon test and linear
      regression model). RESULTS: The experimental group significantly improved their
      spike speed 3.8% from phase A to phase B, and they maintained this improvement
      after the retention phase. No improvements were found in the control group. The
      experimental group presented a significant improvement from phase A to phase B in
      dominant arm muscle area (+10.8%), 1RM for the bench press (+8.41%), 1RM for the
      pullover (+14.75%), and overhead medicine ball throws with 1 kg (+7.19%), 2 kg
      (+7.69%), and 3 kg (+5.26%). The control group did not present differences in
      these variables. CONCLUSIONS: Data showed the plyometric exercises that were
      tested could be used by performance-level volleyball teams to improve spike
      speed. The experimental group increased their upper-body maximal strength, their
      power application, and spike speed.

PMID- 28745473
TI  - Does the aerobic threshold correlate with the maximal fat oxidation rate in short
      stage treadmill tests?
AB  - BACKGROUND: The aim of this study was to identify the exercise intensity that
      elicited the highest rate of fat utilization (FATmax) and to assess its
      relationship with the aerobic threshold (AeT) in male athletes. We hypothesized
      existence of high correlation of these two parameters when a short-staged graded
      treadmill test with AeT identified through breath-by-breath gas exchange analysis
      was used. METHODS: Fifty-six trained male athletes (age 25.6+/-3.4 y, height
      197.8+/-5.6 cm, body mass 98.5+/-6.6 kg) participated in the study. Pearson
      correlation coefficient (r) and effect size (R2) were used to evaluate the
      existence of connection between VO2 at AeT and at FATmax. Maximal oxygen
      consumption (VO2max) and substrate oxidation were determined using breath-by
      breath indirect calorimetry during a short-staged graded treadmill test to
      exhaustion. RESULTS: Mean VO2max was 52.12+/-9.02 mL.kg-1.min-1. FATmax and AeT
      occurred at 47.47+/-10.59% of VO2max and 45.95+/-10.21% of VO2max, respectively.
      Fat utilization at FATmax was 0.59+/-0.24 g.min-1. A high correlation was found
      between VO2 at FATmax and at AeT (r=0.88, P<0.01, 95% CI: 0.80 to 0.93). The
      effect size was 77.44%. CONCLUSIONS: Our results confirm the hypothesis of an
      existence of a high correlation between AeT and FATmax allowing implementation of
      more accurate training approach.

PMID- 28745474
TI  - The use of metabolic power to assess physical demands in soccer: how does it
      differ from the traditional approach through speed running?
AB  - BACKGROUND: Metabolic power and speed running are in the top-10-ranked variables
      used to quantify the physical demand in soccer matches or training practices. The
      main purpose of this study was to compare metabolic power (MP) and the
      traditional approach using speed running during soccer matches in absolute values
      and in zones of intensity in function of the playing positions. METHODS: Thirty
      eight professional soccer players were analyzed during 18 friendly matches from 4
      preseasons (N.=300) and divided into 5 groups of playing positions: central
      defender (CD) (N.=64), wide defender (WD) (N.=55), central midfielder (CM)
      (N.=58), wide attacker (WA) (N.=70), and attacker (AT) (N.=53). The individual
      profiles to each playing positions were assessed using MP and speed running
      approaches. The magnitude of change was substantial when there was a >=75%
      likelihood of the effect. The effect size was also calculated using a confidence
      interval of 90%. RESULTS: In absolute values, CMs and WAs had substantially
      greater values than did the other positions, with CMs having the highest values
      in both approaches and an identical relationship between the positions in both
      approaches. In categories of intensity, medium-low intensity displayed
      differences between the approaches; the physical demands of ATs and CDs were
      lower using the traditional approach but were higher than the other playing
      positions when assessed using MP. No differences were found at low, medium or
      high intensities. CONCLUSIONS: The MP and energy expenditure reported differences
      at medium-low intensity compared to the speed running traditional approach
      between playing positions. However, the other intensities did not report
      differences compared to the traditional approach in the different playing
      positions.

PMID- 28745475
TI  - BodyPump versus traditional heavy load resistance training on changes in resting
      metabolic rate in overweight untrained women.
AB  - BACKGROUND: Moderate to heavy load resistance training (RT) is advocated for
      overweight and obese individuals. One of the beneficial effects of RT is
      increased resting metabolic rate (RMR), which typically makes up the majority of
      the total daily energy expenditure. It is, however, unclear if low to moderate
      load RT affects RMR. Hence, the present study aimed to examine the effects of
      twelve weeks of BodyPump, on RMR in previous untrained women with BMI>=25.0, and
      to compare the results with individual heavy load RT. METHODS: Eighteen
      overweight women participated in the study (mean age 35.4+/-10.2 years, BMI 30.4
      kg/m2+/-4.8), ten allocated to BodyPump (high-repetition, low to moderate load
      RT) and 8 to heavy load RT (linear periodization with 3-6, 8-10 and 13-15
      repetitions, 2-4 series). Both groups exercised 3 times/week for 12 weeks. RMR
      was assessed with indirect calorimetry at baseline, midway (after 6 weeks) and at
      post-test. RESULTS: Adherence to exercise were 62% and 93% in the BodyPump and
      heavy load RT group, respectively (P=0.003). RMR in the BodyPump increased with
      8.5% (+/-10.8) from baseline to post-test (P=0.041). The heavy load RT group
      increased 10.5% (+/-10.4) from baseline to post-test (P=0.025). There was no
      significant group difference in RMR from baseline to post-test (P=0.593).
      CONCLUSIONS: BodyPump and heavy load RT resulted in a similar increase in RMR
      after 12 weeks of training. Assuming that elevation of RMR is important for
      combating overweight and obesity, BodyPump appears to have the same potential as
      heavy load RT.

PMID- 28745476
TI  - Extending Marketplace Tax Credits Would Make Coverage More Affordable for Middle
      Income Adults.
AB  - ISSUE: Affordability of health coverage is a growing challenge for Americans
      facing rising premiums, deductibles, and copayments. The Affordable Care Act's
      tax credits make marketplace insurance more affordable for eligible lower-income
      individuals. However, individuals lose tax credits when their income exceeds 400
      percent of the federal poverty level, creating a steep cliff. GOALS: To analyze
      the effects of extending eligibility for tax credits to individuals with incomes
      above 400 percent of the federal poverty level. METHODS: We used RAND's COMPARE
      microsimulation model to examine changes in insurance coverage and health care
      spending. KEY FINDINGS AND CONCLUSIONS: Extending tax-credit eligibility
      increases insurance enrollment by 1.2 million, at a total federal cost of $6.0
      billion. Those who would benefit from the tax-credit extension are mostly middle
      income adults ages 50 to 64. These new enrollees would be healthier than current
      enrollees their age, which would improve the risk pool and lower premiums.
      Eliminating the cliff at 400 percent of the federal poverty level is one policy
      option that may be considered to increase affordability of insurance.

PMID- 28745477
TI  - Comparison of the Responsivity of Solution-Suspended and Surface-Bound Poly(N
      isopropylacrylamide)-Based Microgels for Sensing Applications.
AB  - In this submission, the phase transition behavior for poly(N-isopropylacrylamide
      co-acrylic acid) (pNIPAm-co-AAc) microgels and their assemblies was investigated
      as a function of temperature and pH using UV-vis spectroscopy (to probe light
      scattering behavior) and quartz crystal microbalance with dissipation (QCM-D)
      measurements. PNIPAm-co-AAc microgels were "painted" onto Au-coated glass
      substrates (for UV-vis) and the Au electrode of a QCM crystal to generate
      monolayers. The subsequent deposition of another Au layer on top of the pNIPAm-co
      AAc microgel layer yields what is known as an etalon. UV-vis/QCM-D measurements
      revealed that the temperature and pH responsivities for the microgel assemblies
      match well with their solution behavior. UV-vis spectroscopy shows that the
      transmittance of the microgel monolayers decreased with increasing solution
      temperature at pH 3.0. At pH 6.5, the AAc groups in the microgels were
      deprotonated, leading to strong Coulombic repulsive forces inside the microgels
      that prevented their collapse and lead to minimal change in the transmitted light
      intensity. However, QCM-D analysis reveals more complex behavior as it is
      sensitive to the viscosity/viscoelasticity and thickness changes of the microgel
      layer, which ultimately depends on the microgel chemical composition and the
      interaction of the etalon's Au layer with the crystal. The maximum sensitivity to
      temperature is 0.8 * 10-3  degrees C.Hz-1, which is the most sensitive pNIPAm
      microgel-based QCM temperature sensor thus far reported in the literature.
      Finally, we exploit this new understanding to characterize the pH and ionic
      strength of a solution using pNIPAm-co-XAAc microgel-based etalon coated
      crystals. The research results and the sensing demonstration can inspire new and
      improved sensor designs for a variety of analytes.

PMID- 28745478
TI  - Improving Dispersion and Barrier Properties of Polyketone/Graphene Nanoplatelet
      Composites via Noncovalent Functionalization Using Aminopyrene.
AB  - A series of polyketone (PK) nanocomposite films with varying content of
      noncovalently functionalized graphene nanoplatelet with 1-aminopyrene (GNP/APy)
      is prepared by solution blending with a solvent of hexafluoro-2-propanol.
      GNP/APy, prepared by a facile method, can effectively induce specific interaction
      such as hydrogen bonding between the amine functional group of GNP/APy and the
      carbonyl functional group of the PK matrix. With comparison of GNP and GNP/Py as
      reference materials, intensive investigation on filler-matrix interaction is
      achieved. In addition, the dispersion state of the functionalized GNP (f-GNPs;
      GNP/Py and GNP/APy) in the PK matrix is analyzed by three-dimensional
      nondestructive X-ray microcomputed tomography, and the increased dispersion state
      of those fillers results in significant improvement in the water vapor
      transmission rate (WVTR). The enhancement in WVTR of the PK/GNP/APy nanocomposite
      film at 1 wt % loading of filler leads to a barrier performance approximately 2
      times larger compared to that of PK/GNP nanocomposite film and an approximately
      92% reduction in WVTR compared to the case of pristine PK film. We expect that
      this facile method of graphene functionalization to enhance graphene
      dispersibility as well as interfacial interaction with the polymer matrix will be
      widely utilized to expand the potential of graphene materials to barrier film
      applications.

PMID- 28745479
TI  - Visualizing Local Morphology and Conductivity Switching in Interface-Assembled
      Nanoporous C60 Thin Films.
AB  - Carbon materials promise a revolution in optoelectronics, medical applications,
      and sensing provided that their morphology can be controlled down to the
      nanometer scale. Nanoporous materials are particularly appealing as they offer a
      drastically enlarged interfacial area compared to the corresponding planar
      materials. Entire fields such as organic solar cells, catalysis, or sensing may
      profit from an enlarged interface and facilitated molecular interaction between a
      carbon material and the environment. Nanoporous fullerene thin films obtained by
      the deposition of suspended nanoclusters of fullerene were already reported but
      suffered from the limitation of the size of these particles to over 100 nm. We
      study here a complementary method based on interfacial self-assembly forcing C60
      clusters to spontaneously form 2D percolating monolayers with most morphological
      features in the 5-20 nm range. Analysis of these films by means of electron
      microscopy and scanning probe microscopy proved their morphology to be a
      nanocomposite of crystalline beads embedded in an amorphous matrix of fullerenes.
      When contacted between two gold electrodes, these films show an intrinsic
      conductivity switching behavior. Their electrical conductivity could be
      reversibly switched on by applying a threshold electrical current and switched
      off by exposure to oxygen. Interestingly, the on-state exhibits an astonishing
      conductivity of over 10-3 S/m. Kelvin probe force microscopy (KFM) was used to
      observe local changes in the distribution of electrical potential upon switching,
      on the relevant length scale of a few nanometers.

PMID- 28745480
TI  - Controllable Photovoltaic Effect of Microarray Derived from Epitaxial Tetragonal
      BiFeO3 Films.
AB  - Recently, the ferroelectric photovoltaic (FePV) effect has attracted great
      interest due to its potential in developing optoelectronic devices such as solar
      cell and electric-optical sensors. It is important for actual applications to
      realize a controllable photovoltaic process in ferroelectric-based materials. In
      this work, we prepared well-ordered microarrays based on epitaxially tetragonal
      BiFeO3 (T-BFO) films by the pulsed laser deposition technique. The polarization
      dependent photocurrent image was directly observed by a conductive atomic force
      microscope under ultraviolet illumination. By choosing a suitable buffer
      electrode layer and controlling the ferroelectric polarization in the T-BFO
      layer, we realized the manipulation of the photovoltaic process. Moreover, based
      on the analysis of the band structure, we revealed the mechanism of manipulating
      the photovoltaic process and attributed it to the competition between two key
      factors, i.e., the internal electric field caused by energy band alignments at
      interfaces and the depolarization field induced by the ferroelectric polarization
      in T-BFO. This work is very meaningful for deeply understanding the photovoltaic
      process of BiFeO3-based devices at the microscale and provides us a feasible
      avenue for developing data storage or logic switching microdevices based on the
      FePV effect.

PMID- 28745481
TI  - Fluorine Doping Strengthens the Lithium-Storage Properties of the Mn-Based Metal
      Organic Framework.
AB  - The electrochemical properties of the metal-organic framework (MOF)-based
      composite as electrode material can be significantly improved by means of partial
      destruction of the full coordination of linkers to metal ions and replacing with
      other small ions, which make metal centers become more accostable and
      consequently more effective for the lithiation/delithiation process. In this
      paper, F- was chosen to replace some of the benzenedicarboxylate (BDC) linkers
      because of its better interaction with the Li+ than the oxide ion. What's more,
      the formed M-F bond promotes the Li+ to transfer at the active material interface
      and protects the surface from HF attacking. The as-synthesized F-doped Mn-MOF
      electrode maintains a reversible capacity of 927 mA h g-1 with capacity retention
      of 78.5% after 100 cycles at 100 mA g-1 and also exhibits a high discharge
      capacity of 716 mA h g-1 at 300 mA g-1 and 620 mA h g-1 at 500 mA g-1 after 500
      cycles. Even at 1000 mA g-1, the electrode still maintains a high reversible
      capacity of 494 mA h g-1 after 500 cycles as well as a Coulombic efficiency of
      nearly 100%, which is drastically increased compared with pure Mn-MOF material as
      expected.

PMID- 28745482
TI  - Near-Infrared Triggered Upconversion Polymeric Nanoparticles Based on Aggregation
      Induced Emission and Mitochondria Targeting for Photodynamic Cancer Therapy.
AB  - Photodynamic therapy (PDT) is an auspicious strategy for cancer therapy by
      yielding reactive oxygen species (ROS) under light irradiation. Here, we have
      developed near-infrared (NIR) triggered polymer encapsulated upconversion
      nanoparticles (UCNPs) based on aggregation-induced emission (AIE) characteristics
      and mitochondria target ability for PDT. The coated AIE polymer as a
      photosensitizer can be photoactivated by the up-converted energy of UCNPs upon
      980 nm laser irradiation, which could generate ROS efficiently in mitochondria
      and induce cell apoptosis. Moreover, a "sheddable" poly(ethylene glycol) (PEG)
      layer was easily conjugated at the surface of NPs. The pH-responsive PEG layer
      shields the surface positive charges and shows stronger protein-resistance
      ability. In the acidic tumor environment, PEGylated NPs lose the PEG layer and
      show the mitochondria-targeting ability by responding to tumor acidity. A
      cytotoxicity study indicated that these NPs have good biocompatibility in the
      dark but exert severe cytotoxicity to cancer cells, with only 10% cell viability,
      upon being irradiated with an NIR laser. The AIE nanoparticles are a good
      candidate for effective mitochondria targeting photosensitizer for PDT.

PMID- 28745483
TI  - Postsynthetic Modification of ZIF-90 for Potential Targeted Codelivery of Two
      Anticancer Drugs.
AB  - Combination therapy has been regarded as a promising strategy for cancer
      treatment due to the enhanced anticancer efficacy achieved by blocking multiple
      drug resistance pathways. In this work, a drug carrier based on nanoscale ZIF-90
      for the codelivery of two anticancer drugs has been synthesized by covalently
      attaching doxorubicin (DOX) to the surface of ZIF-90 via Schiff base reaction of
      amino group in DOX and aldehyde group of imidazole-2-carboxaldehyde (ICA) ligand
      and encapsulating 5-fluorouracil (5-FU) into the pores of the framework. The
      results of drug loading measurements show that the loading amount of drugs was
      estimated as high as 36.35 and 11-13.5 wt % for 5-FU and DOX, respectively.
      Moreover, we demonstrated that the carrier had the potential of cancer-targeted
      delivery of drugs for the collapse of framework under the pH environment around
      cancer cells and subsequently releasing drugs. Drug release at pH 5.5, imitating
      the environment of tumor, can reach over 95%, and the release time is less 16 h,
      meaning a more effective and faster release of drugs around tumoral cells than
      that in a normal environment. This is the first report for cancer-targeted
      codelivery of two different chemical drugs based on nanoscale metal-organic
      frameworks (NMOFs).

PMID- 28745484
TI  - Spinels: Controlled Preparation, Oxygen Reduction/Evolution Reaction Application,
      and Beyond.
AB  - Spinels with the formula of AB2O4 (where A and B are metal ions) and the
      properties of magnetism, optics, electricity, and catalysis have taken
      significant roles in applications of data storage, biotechnology, electronics,
      laser, sensor, conversion reaction, and energy storage/conversion, which largely
      depend on their precise structures and compositions. In this review, various
      spinels with controlled preparations and their applications in oxygen
      reduction/evolution reaction (ORR/OER) and beyond are summarized. First, the
      composition and structure of spinels are introduced. Then, recent advances in the
      preparation of spinels with solid-, solution-, and vapor-phase methods are
      summarized, and new methods are particularly highlighted. The physicochemical
      characteristics of spinels such as their compositions, structures, morphologies,
      defects, and substrates have been rationally regulated through various
      approaches. This regulation can yield spinels with improved ORR/OER catalytic
      activities, which can further accelerate the speed, prolong the life, and narrow
      the polarization of fuel cells, metal-air batteries, and water splitting devices.
      Finally, the magnetic, optical, electrical, and catalytic applications beyond the
      OER/ORR are also discussed. The future applications of spinels are considered to
      be closely related to environmental and energy issues, which will be aided by the
      development of new species with precise preparations and advanced
      characterizations.

PMID- 28745485
TI  - Nanoparticle Analysis by Online Comprehensive Two-Dimensional Liquid
      Chromatography combining Hydrodynamic Chromatography and Size-Exclusion
      Chromatography with Intermediate Sample Transformation.
AB  - Polymeric nanoparticles have become indispensable in modern society with a wide
      array of applications ranging from waterborne coatings to drug-carrier-delivery
      systems. While a large range of techniques exist to determine a multitude of
      properties of these particles, relating physicochemical properties of the
      particle to the chemical structure of the intrinsic polymers is still
      challenging. A novel, highly orthogonal separation system based on comprehensive
      two-dimensional liquid chromatography (LC * LC) has been developed. The system
      combines hydrodynamic chromatography (HDC) in the first-dimension to separate the
      particles based on their size, with ultrahigh-performance size-exclusion
      chromatography (SEC) in the second dimension to separate the constituting polymer
      molecules according to their hydrodynamic radius for each of 80 to 100 separated
      fractions. A chip-based mixer is incorporated to transform the sample by
      dissolving the separated nanoparticles from the first-dimension online in
      tetrahydrofuran. The polymer bands are then focused using stationary-phase
      assisted modulation to enhance sensitivity, and the water from the first
      dimension eluent is largely eliminated to allow interaction-free SEC. Using the
      developed system, the combined two-dimensional distribution of the particle-size
      and the molecular-size of a mixture of various polystyrene (PS) and polyacrylate
      (PACR) nanoparticles has been obtained within 60 min.

PMID- 28745486
TI  - High Crystallization of Perovskite Film by a Fast Electric Current Annealing
      Process.
AB  - High-efficiency organic-inorganic hybrid perovskite solar cells have experienced
      rapid development and attracted significant attention in recent years. Crystal
      growth as an important factor would significantly influence the quality of
      perovskite films and ultimately the device performance, which usually requires
      thermal annealing for 10 min or more. Herein, we demonstrate a new method to get
      high crystallization of perovskite film by electric current annealing for just 5
      s. In contrast to conventional thermal annealing, a homogeneous perovskite film
      was formed with larger grains and fewer pinholes, leading to a better performance
      of the device with higher open-circuit voltage and fill factor. An average power
      conversion efficiency of 17.02% with electric current annealing was obtained,
      which is higher than that of devices with a conventional thermal annealing
      process (16.05%). This facile electric current annealing process with less energy
      loss and time consumption shows great potential in the industrial mass production
      of photovoltaic devices.

PMID- 28745487
TI  - Self-Climbed Amorphous Carbon Nanotubes Filled with Transition Metal Oxide
      Nanoparticles for Large Rate and Long Lifespan Anode Materials in Lithium Ion
      Batteries.
AB  - A composed material of amorphous carbon nanotubes (ACNTs) and encapsulated
      transition metal oxide (TMOs) nanoparticles was prepared by a common
      thermophysics effect, which is named the Marangoni effect, and a simple anneal
      process. The prepared ropy solution would form a Marangoni convection and climb
      into the channel of anodic aluminum oxide template (AAO) spontaneously. The
      ingenious design of the preparation method determined a distinctive structure of
      TMOs nanoparticles with a size of ~5 nm and amorphous carbon coated outside full
      in the ACNTs. Here we prepared the ferric oxide (Fe2O3) nanoparticles and Fe2O3
      mixed with manganic oxide (Fe2O3&Mn2O3) nanoparticles encapsulated in ACNTs as
      two anode materials of lithium ion batteries' the TMOs-filled ACNTs presented an
      evolutionary electrochemical performance in some respects of highly reversible
      capacity and excellent cycling stability (880 mA h g-1 after 150 cycles).

PMID- 28745488
TI  - Fabrication of TiO2-Reduced Graphene Oxide Nanorod Composition Spreads Using
      Combinatorial Hydrothermal Synthesis and Their Photocatalytic and
      Photoelectrochemical Applications.
AB  - This study is the first to employ combinatorial hydrothermal synthesis and facile
      spin-coating technology to fabricate TiO2-reduced graphene oxide (rGO) nanorod
      composition spreads. The features of this study are (1) the development of a self
      designed spin-coating wedge, (2) the systemic investigation of the structure
      property relationship of the system, (3) the high-throughput screening of the
      optimal ratio from a wide range of compositions for photocatalytic and
      photoelectrochemical (PEC) applications, and (4) the effective coupling between
      the density gradient TiO2 nanorod array and the thickness gradient rGO. The
      formation of rGO in the fabricated TiO2-rGO sample was monitored through Fourier
      transform infrared spectrometry. Transmission electron microscopy images also
      suggested that the TiO2 nanorod surfaces were covered with a thin layer of
      amorphous rGO. The rutile TiO2 plane evolution along the composition variation
      was verified through X-ray diffraction. 7% TiO2-93% rGO on the nanorod
      composition spread exhibited the most promising photocatalytic ability; the
      corresponding photodegradation kinetics, denoted by the photodegradation rate
      constant (k), was determined to be approximately 12.7 * 10-3 min-1. The excellent
      performance was attributed to the effective coupling between the TiO2 and rGO,
      which improved the charge carrier transport, thus inhibiting electron-hole pair
      recombination. A cycling test implied that 7% TiO2-93% rGO is a reliable
      photocatalyst. A photoluminescence spectroscopy study also supported the superior
      photocatalytic ability of the sample, which was attributed to its markedly poorer
      recombination behavior. In addition, without further treatment, the sample
      exhibited excellent PEC stability; the photocurrent density was more than three
      times higher than that exhibited by the density gradient TiO2 nanorods.

PMID- 28745490
TI  - Switchable Target-Responsive 3D DNA Hydrogels As a Signal Amplification Strategy
      Combining with SERS Technique for Ultrasensitive Detection of miRNA 155.
AB  - Usually, SERS technology requires labeling of the Raman reporter to obtain
      characteristic spectra for detection of biological samples. However, the number
      of labeled Raman reporters is often limited, resulting in the restricted
      improvement for sensitivity of SERS biosensor. In this work, switchable target
      responsive 3D DNA hydrogels were introduced to precisely control trapping and
      release of Raman reporter toluidine blue (TB), which not only avoid labeling
      signal molecule but also improve the sensitivity of miRNA detection due to
      immobilization of abundant TB. In the absence of target miRNA, the DNA hydrogel
      presented a weak Raman signal because TB was far away from SERS substrates with
      an "OFF" status. However, the DNA hydrogel can be opened by the target miRNA to
      release TB producing strong Raman signal with an "ON" status. On the basis of
      this sensitive strategy, this switchable DNA hydrogel-based SERS platform can
      achieve quantitative detection of miRNA 155. Simultaneously, flexible SERS
      substrate (leaf@nafion@Ag) and target miRNA-induced duplex-specific nuclease
      signal amplification strategy were employed to significantly improve the
      sensitivity of the SERS platform. As a result, the as-proposed SERS platform can
      sensitively and selectively detect miRNA 155 with a wide linear range of 0.1 fM
      to 100 pM and low detection limit of 0.083 fM, which indicated that the platform
      has great potential to be applied in miRNA-related clinical diagnostics and
      biochemical researches.

PMID- 28745489
TI  - The Dihydroxy Metabolite of the Teratogen Thalidomide Causes Oxidative DNA
      Damage.
AB  - Thalidomide [alpha-(N-phthalimido)glutarimide] (1) is a sedative and antiemetic
      drug originally introduced into the clinic in the 1950s for the treatment of
      morning sickness. Although marketed as entirely safe, more than 10 000 babies
      were born with severe birth defects. Thalidomide was banned and subsequently
      approved for the treatment of multiple myeloma and complications associated with
      leprosy. Although known for more than 5 decades, the mechanism of teratogenicity
      remains to be conclusively understood. Various theories have been proposed in the
      literature including DNA damage and ROS and inhibition of angiogenesis and
      cereblon. All of the theories have their merits and limitations. Although the
      recently proposed cereblon theory has gained wide acceptance, it fails to explain
      the metabolism and low-dose requirement reported by a number of groups. Recently,
      we have provided convincing structural evidence in support of the presence of
      arene oxide and the quinone-reactive intermediates. However, the ability of these
      reactive intermediates to impart toxicity/teratogenicity needs investigation.
      Herein we report that the oxidative metabolite of thalidomide,
      dihydroxythalidomide, is responsible for generating ROS and causing DNA damage.
      We show, using cell lines, the formation of comet (DNA damage) and ROS. Using DNA
      cleavage assays, we also show that catalase, radical scavengers, and desferal are
      capable of inhibiting DNA damage. A mechanism of teratogenicity is proposed that
      not only explains the DNA-damaging property but also the metabolism, low
      concentration, and species-specificity requirements of thalidomide.

PMID- 28745491
TI  - Controlled Construction of Supported Cu+ Sites and Their Stabilization in MIL
      100(Fe): Efficient Adsorbents for Benzothiophene Capture.
AB  - Cu+-containing materials have drawn much attention in various applications
      because they are versatile, nontoxic, and low-cost. However, the difficulty of
      selective reduction and the poor stability of Cu+ species are now pretty much the
      agendas. Here, controlled construction of supported Cu+ sites in MIL-100(Fe) was
      realized under mild conditions (200  degrees C, 5 h) via a vapor-reduction
      strategy (VRS). Remarkably, the yield of Cu+ reaches 100%, which is quite higher
      than the traditional high-temperature autoreduction method with a yield less than
      50% even at 700  degrees C for 12 h. More importantly, during the treatment via
      VRS some Fe3+ in MIL-100(Fe) are reduced to Fe2+, which prevent the frequently
      happened oxidation of Cu+ due to the higher oxidation potential of Fe2+. These
      properties make Cu+/MIL-100(Fe) efficient in the capture of typical aromatic
      sulfur, benzothiophene, with regard to both adsorption capacity and stability. To
      our knowledge, the stabilization of Cu+ using the oxidation tendency of supports
      is achieved for the first time, which may offer a new idea to utilize active
      sites with weak stability.

PMID- 28745492
TI  - Amphiphilic Polysaccharide Block Copolymers for pH-Responsive Micellar
      Nanoparticles.
AB  - A full polysaccharide amphiphilic block copolymer was prepared from end group
      functionalized dextrans using copper-mediated azide-alkyne click chemistry.
      Sufficient modification of the reducing end in both blocks was achieved by
      microwave-enhanced reductive amination in a borate-buffer/methanol solvent
      system. The combination of a hydrophilic dextran block with a hydrophobic
      acetalated dextran block results in an amphiphilic structure that turns water
      soluble upon acid treatment. The material has a low critical micelle
      concentration and self-assembles in water to spherical micellar nanoparticles.
      The formed nanoparticles have a narrow size distribution below 70 nm in diameter
      and disassemble in slightly acidic conditions. The amphiphilic polysaccharide
      system shows low toxicity and can stabilize the hydrophobic model drug curcumin
      in aqueous solutions over extended time periods.

PMID- 28745493
TI  - Sortase-Mediated Surface Functionalization of Stimuli-Responsive Microgels.
AB  - In this work we explored an enzyme-mediated method for selective and efficient
      decoration of aqueous microgels with biomolecules. Poly(N-vinylcaprolactam) (VCL)
      microgels with varied amounts of glycidyl methacrylate (GMA) as comonomer
      incorporated in the microgel shell were synthesized and characterized in regard
      to their size, swelling degree, and temperature-responsiveness in aqueous
      solutions. The surface of the PVCL/GMA microgel containing 5 mol % glycidyl
      methyacrylate was modified by grafting of a specific recognition peptide sequence
      (LPETG) for Sortase A from Staphylococcus aureus (Sa-SrtADelta59). Sortase
      mediated conjugation of the enhanced Green Fluorescent Protein (eGFP) carrying a
      N-terminal triglycine tag to LPETG-modified microgels was successfully performed.
      Conjugation of eGFP to the microgel surface was qualitatively proven by confocal
      microscopy and by fluorescence intensity measurements. The developed protocol
      enables a precise control of the amount of eGFP grafted to the microgel surface
      as evidenced by the linear increase of fluorescence intensity of modified
      microgel samples. The kinetic of the sortase-mediated coupling reaction was
      determined by time-dependent fluorescence intensity measurements. In summary,
      sortase-mediated coupling reactions are a simple and powerful technique for
      targeted surface functionalization of stimuli-responsive microgels with
      biomolecules.

PMID- 28745494
TI  - Surface-Anchored Thiol-Reactive Soft Interfaces: Engineering Effective Platforms
      for Biomolecular Immobilization and Sensing.
AB  - Fabrication of antibiofouling, specifically reactive polymeric coatings that
      undergo facile functionalization with thiol-bearing small molecules and ligands,
      yields effective platforms for biomolecular immobilization and sensing.
      Poly(ethylene glycol) (PEG)-based copolymers containing alkoxysilyl groups to
      enable surface-anchoring and furan-protected maleimide groups as latent thiol
      reactive moieties as side-chains were synthesized. Reactive interfaces were
      obtained by coating these copolymers onto Si/SiO2 or glass surfaces and
      activating the maleimide groups to their thiol-reactive forms via thermal
      treatment. A series of surfaces modified with copolymers containing varying
      amounts of maleimide groups were synthesized. Effectiveness of surface
      modification was probed using Fourier transform infrared spectroscopy, contact
      angle goniometry, ellipsometry and X-ray photoelectron spectroscopy. Facile
      surface modification through thiol-maleimide conjugation was established by
      attachment of a thiol-containing fluorescent dye, namely BODIPY-SH. It was
      demonstrated that these surfaces allow spatially localized modification through
      microcontact printing. Importantly, the extent of surface modification could be
      tuned by varying the initial composition of the copolymer used for coating. Using
      fluorescence microscopy, it was observed that increasing amount of fluorescent
      dye was attached onto surfaces fabricated with copolymers with increasing amount
      of masked maleimide groups. Thereafter, the thiol-maleimide conjugation was
      utilized to decorate these surfaces with biotin, a protein-binding ligand. It was
      observed that though these biotinylated surfaces were able to bind Streptavidin
      effectively, some nonspecific binding was observed on places that were not in
      conformal contact with the stamp during microcontact printing. This nonspecific
      binding was eliminated upon neutralizing the residual maleimide units on the
      printed surface using thiol-containing PEG. Notably, fluorescence analysis of
      Streptavidin immobilized onto biotinylated surfaces fabricated using varying
      amounts of maleimide demonstrated that the amount of immobilized protein could be
      tuned by varying surface composition. It can be envisioned that facile
      fabrication of these maleimide-containing polymeric surfaces, their effective
      functionalization in a tunable manner to engineer interfaces for effective
      immobilization or sensing of biomolecules in a spatially controlled manner would
      make them attractive candidates for various biotechnological applications.

PMID- 28745495
TI  - Kinetic Switching of the Concentration/Separation Behavior of Microdroplets.
AB  - This work demonstrates that the solute concentration inside 100 micrometer-sized
      aqueous microdroplets can be controlled by adjusting the time required for the
      aqueous nanometer-sized droplets (nanodroplet) or reverse micelles to pass over
      the surface of the microdroplet. The kinetics of molecular transport between the
      microdroplets and the nanodroplets was investigated by utilizing a microdroplet
      array, and on the basis of these results, a control over the concentration
      selectivity of the contents of the microdroplet was achieved. This method is
      operationally simple and can be potentially applied as a pretreatment method for
      microanalytical systems that require high-density microdroplet arrays. This
      method can also be utilized for parallel small sample analyses such as single
      cell analysis.

PMID- 28745496
TI  - Freshwater Vulnerability beyond Local Water Stress: Heterogeneous Effects of
      Water-Electricity Nexus Across the Continental United States.
AB  - Human health and economic prosperity are vulnerable to freshwater shortage in
      many parts of the world. Despite a growing literature that examines the
      freshwater vulnerability in various spatiotemporal contexts, existing knowledge
      has been conventionally constrained by a territorial perspective. On the basis of
      spatial analyses of monthly water and electricity flows across 2110 watersheds
      and three interconnected power systems, this study investigates the water
      electricity nexus (WEN)'s transboundary effects on freshwater vulnerability in
      the continental United States in 2014. The effects are shown to be considerable
      and heterogeneous across time and space. For at least one month a year, 58
      million people living in water-abundant watersheds were exposed to additional
      freshwater vulnerability by relying on electricity generated by freshwater-cooled
      thermal energy conversion cycles in highly stressed watersheds; for 72 million
      people living in highly stressed watersheds, their freshwater vulnerability was
      mitigated by using imported electricity generated in water-abundant watersheds or
      power plants running dry cooling or using nonfreshwater for cooling purposes. On
      the country scale, the mitigation effects were the most significant during
      September and October, while the additional freshwater vulnerability was more
      significant in February, March, and December. Due to the WEN's transboundary
      effects, overall, the freshwater vulnerability was slightly worsened within the
      Eastern Interconnection, substantially improved within the Western
      Interconnection, and least affected within the ERCOT Interconnection.

PMID- 28745497
TI  - Activity of Isoliensinine in Improving the Symptoms of Type 2 Diabetic Mice via
      Activation of AMP-Activated Kinase and Regulation of PPARgamma.
AB  - This study was designed to explore the effects and mechanism of isoliensinine
      (isolie) from embryos of Nelumbo nucifera on type 2 diabetes and dyslipidemia in
      vivo and in vitro. The in vitro study showed that isolie increased the GLUT4
      translocation by 2.5-fold in L6 cells. Furthermore, after 4 weeks of treatment,
      the in vivo biochemical study indexes revealed that isolie had a positive effect
      on decreasing serum insulin level (42.2 +/- 5.10 vs 55.7 +/- 6.33 mU/L, P < 0.05)
      and reducing fast blood glucose (9.4 +/- 1.5 vs 18.7 +/- 2.3 mmol/L, P < 0.001)
      and body weight (37.8 +/- 2.9 vs 46.9 +/- 5.4 g, P < 0.05) compared with the KK
      Ay model mice. Isolie treatment led to significant increases in GLUT4 proteins
      (~2.7-fold in skeletal muscle and ~2.4-fold in WAT) and phosphorylated AMP
      activated protein kinase (~1.4-fold in skeletal muscle, ~3.1-fold in WAT, and
      ~2.3-fold in liver). However, isolie caused a significant decrease in lipogenesis
      protein expressions of PPARgamma and SREBP-1c, and decreased the activity of ACC
      by increasing the phospho-ACC level. Our findings showed that isolie has the
      potential to alleviate type 2 diabetes associated with hyperlipidemia in KK-Ay
      mice. Regulation of GLUT4, SREBP-1c, PPARgamma, AMPK phosphorylation, and ACC
      phosphorylation is implicated in the antidiabetic effects of isolie.

PMID- 28745498
TI  - Curcumin and Salsalate Suppresses Colonic Inflammation and Procarcinogenic
      Signaling in High-Fat-Fed, Azoxymethane-Treated Mice.
AB  - High-fat diets (HFDs) and excess adiposity increase proinflammatory cytokines in
      the colon, altering gene expression in a manner that promotes the development of
      colorectal cancer (CRC). Thus, compounds that reduce this biochemical
      inflammation are potential chemopreventive agents. Curcumin (CUR), a dietary
      polyphenol, and salsalate (SAL), a non-steroidal anti-inflammatory drug, are both
      anti-inflammatories. We investigated the inhibitory effects of CUR with or
      without SAL on inflammatory cytokines and procarcinogenic signaling in
      azoxymethane (AOM)-treated A/J mice. A sub-tumorigenic AOM dose was chosen to
      produce a biochemical and molecular procarcinogenic colonic environment without
      tumors. Mice were fed either a HFD (60% of kilocalories) or low-fat diet (LFD)
      (10% of kilocalories). One HFD treatment group received 0.2% CUR in the diet; one
      received 0.2% CUR + 0.15% SAL; and one received 0.4% CUR + 0.3% SAL. The HFD mice
      developed 30% greater fat mass than the LFD mice (p < 0.05). The colonic
      concentrations of interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in the
      HFD mice were decreased by 50-69% by the high-dose combination regimen (p <
      0.015). Only the combination regimens significantly suppressed phosphorylation of
      protein kinase B (Akt) and nuclear factor-kappaB (NF-kappaB) p65 (p < 0.044). The
      combination of CUR and SAL reduces the concentration of proinflammatory cytokines
      and diminishes activation of Akt and NF-kappaB more effectively than CUR alone,
      providing a scientific basis for examining whether this combination mitigates the
      risk of CRC in obese individuals.

PMID- 28745499
TI  - Valuing the Air Quality Effects of Biochar Reductions on Soil NO Emissions.
AB  - While it is clear that biochar can alter soil N2O emissions, data on NO impacts
      are scarce. Reports range from 0 to 67% soil NO emission reductions postbiochar
      amendment. We use regional air quality and health cost models to assess how these
      soil NO reductions could influence U.S. air quality and health costs. We find
      that at 67% soil NO reduction, widespread application of biochar to fertilized
      agricultural soils could reduce O3 by up to 2.4 ppb and PM2.5 by up to 0.15
      MUg/m3 in some regions. Modeled biochar-mediated health benefits are up to $4.3
      million/county in 2011, with impacts focused in the Midwest and Southwest. These
      potential air quality and health cobenefits of biochar use highlight the need for
      an improved understanding of biochar's impacts on soil NO emissions. The benefits
      reported here should be included with estimates of other biochar benefits, such
      as crop yield increase, soil water management, and N2O reductions.

PMID- 28745500
TI  - Discriminating Catalytically Active FeNx Species of Atomically Dispersed Fe-N-C
      Catalyst for Selective Oxidation of the C-H Bond.
AB  - Nanostructured Fe-N-C materials represent a new type of "platinum-like" non-noble
      metal catalyst for various electrochemical reactions and organic transformations.
      However, no consensus has been reached on the active sites of the Fe-N-C
      catalysts because of their heterogeneity in particle size and composition. In
      this contribution, we have successfully prepared atomically dispersed Fe-N-C
      catalyst, which exhibited high activity and excellent reusability for the
      selective oxidation of the C-H bond. A wide scope of substrates, including
      aromatic, heterocyclic, and aliphatic alkanes, were smoothly oxidized at room
      temperature, and the selectivity of corresponding products reached as high as
      99%. By using sub-angstrom-resolution HAADF-STEM in combination with XPS, XAS,
      ESR, and Mossbauer spectroscopy, we have provided solid evidence that Fe is
      exclusively dispersed as single atoms via forming FeNx (x = 4-6) and that the
      relative concentration of each FeNx species is critically dependent on the
      pyrolysis temperature. Among them, the medium-spin FeIIIN5 affords the highest
      turnover frequency (6455 h-1), which is at least 1 order of magnitude more active
      than the high-spin and low-spin FeIIIN6 structures and 3 times more active than
      the FeIIN4 structure, although its relative concentration in the catalysts is
      much lower than that of the FeIIIN6 structures.

PMID- 28745501
TI  - Free Energy Methods in Drug Design: Prospects of "Alchemical Perturbation" in
      Medicinal Chemistry.
AB  - Underpinning all drug discovery projects is the interaction between a drug and
      its target, usually a protein. Thus, improved methods for predicting the
      magnitude of protein-ligand interactions have the potential to improve the
      efficiency of drug development. In this review, we describe the principles of
      free energy methods used for the calculation of protein-ligand binding free
      energies, the challenges associated with these methods, and recent advances
      developed to address these difficulties. We then present case studies from 2005
      to 2017, each demonstrating that alchemical free energy methods can assist
      rational drug design projects. We conclude that alchemical methods are becoming a
      feasible reality in medicinal chemistry research due to improved computational
      resources and algorithms and that alchemical free energy predictions methods are
      close to becoming a mainstream tool for medicinal chemists.

PMID- 28745502
TI  - Versatile Luminescent Europium(III)-beta-Diketonate-imidazo-bipyridyl Complexes
      Intended for White LEDs: A Detailed Photophysical and Theoretical Study.
AB  - Three ancillary ligands based on imidazo-bipyridyl with phenyl (Ph), naphthyl
      (Np), and triphenylamine (TPA) substitution were synthesized and secondhand to
      formulate the consistent europium(III) ternary complexes using
      thenoyltrifluoroacetone as an anionic ligand. The complete investigation of
      spectroscopic, photophysical, and electrochemical properties was carried out. The
      attained results for all the ancillary ligands and their corresponding Eu
      complexes were compared with one another. All the Eu complexes reveal a broad
      excitation band ranging from the near-UV to blue region, along with high intense
      emission and apposite color purity. To further understand the ligand-to-metal
      energy transfer (ET) process, the geometry of the ligand was optimized and the
      energy level location (singlet and triplet) was calculated by using DFT and TD
      DFT calculations. On the basis of the theoretical calculation, the ET mechanism
      was proposed. From PL emission spectra in the solid state, complete ET occurs
      from Ph, Np based ancillary ligands to the Eu3+ ion, which yields a pure red
      emission, whereas the TPA functionalized based Eu complex shows incomplete ET.
      Fortunately, white emission was observed in the TPA based Eu complex in the solid
      state. The white LED was fabricated by using a white emitting complex integrated
      with 395 nm emitted LED (InGaN) chips under 20 mA forward-bias current. The
      excitation source from LED was fully observed by the complex shown for 3Eu and
      showed yellowish emission in different concentrations (the similar observation
      also reflected in solid). However, in the case of 1Eu and 2Eu complexes, they
      showed close to white emission. The Commission International de I'Eclairage (CIE)
      chromaticity coordinates are close to the National Television Standard Committee
      standard value for white emission, and in addition, the complex 3Eu coated with
      the blue LED chip (460 nm) by PMMA (1:10) showed bright white emission with CIE
      x, y values of 0.30, 0.33, respectively.

PMID- 28745503
TI  - Correction to "Experimental and Theoretical Investigations of Infrared Multiple
      Photon Dissociation Spectra of Asparagine Complexes with Zn2+ and Cd2+ and Their
      Deamidation Processes".

PMID- 28745504
TI  - Xanthohumol Restores Hepatic Glucolipid Metabolism Balance in Type 1 Diabetic
      Wistar Rats.
AB  - Diabetes exhibits increased inflammation, angiogenesis, and apoptosis, three
      processes attenuated by xanthohumol (XN). Herein, we evaluate the effect of XN
      enriched stout beer consumption in hepatic glucolipid metabolism imbalance seen
      in type 1 diabetes (T1D). Five groups of Wistar rats were established:
      streptozotocin-induced diabetic rats drinking water, treated with 5% ethanol,
      stout beer, and stout beer supplemented with 10 mg of XN/L and healthy rats
      drinking water. Hepatic periodic acid-Schiff, reticulin, sirius red, and oil red
      O histological staining was performed. Lipogenic enzymes and glucose transporter
      2 (GLUT2) expression was evaluated by western blotting. Increased fibrosis in T1D
      animals was significantly decreased to control levels by XN (3.85 +/- 0.38 in T1D
      beer versus 1.78 +/- 0.27 in controls, p < 0.05; 2.27 +/- 0.69 in T1D-beer + XN
      versus 1.78 +/- 0.27 in controls, p > 0.05). XN reduced T1D hepatic reticulin
      staining (9.74 +/- 3.78 in T1D-beer, p < 0.05 versus control) to healthy levels
      (4.45 +/- 1.05 in T1D-beer + XN versus 4.60 +/- 0.20 in healthy controls, p >
      0.05). XN consumption interfered with the T1D liver catabolic state, reversing
      glycogen depletion (22.09 +/- 7.70 in T1D-beer + XN versus 4.68 +/- 4.84 in T1D
      beer, p < 0.05) and GLUT2 upregulation (1.71 +/- 0.46 in T1D-beer + XN versus
      2.13 +/- 0.34 in T1D-beer, p < 0.05) and enhancing lipogenesis (1.19 +/- 0.11 in
      T1D-beer + XN versus 1.96 +/- 0.36 in T1D, p < 0.05 for acetyl-CoA carboxylase;
      1.10 +/- 0.04 in T1D-beer + XN versus 0.44 +/- 0.31 in T1D, p < 0.05 for fatty
      acid synthase). These findings reveal that XN can be a therapeutic agent against
      liver metabolic changes in T1D, playing a possible role in the insulin receptor
      pathways.

PMID- 28745505
TI  - Iron-Catalyzed Direct C3-Benzylation of Indoles with Benzyl Alcohols through
      Borrowing Hydrogen.
AB  - We present the coupling of primary and secondary benzyl alcohols with indoles to
      form 3-benzylated indoles and H2O that is catalyzed, for the first time, by a
      complex of earth-abundant iron. This transformation accommodates a variety of
      substrates and is distinguished by its operational simplicity, sustainability,
      high functional-group tolerance, and amenability to gram-scale synthesis. On the
      basis of the preliminary experimental observations, we propose that the reaction
      proceeds through a borrowing hydrogen process.

PMID- 28745506
TI  - Structure-Dependent Hematological Effects of Per- and Polyfluoroalkyl Substances
      on Activation of Plasma Kallikrein-Kinin System Cascade.
AB  - Per- and polyfluoroalkyl substances (PFASs) are a global concern because of their
      ubiquitous occurrence and high persistence in human blood, and increasing amounts
      of unidentified fluorinated compounds are now becoming new exposure issues. This
      study aims to investigate the structure-related effects of PFASs on the
      activation of the plasma kallikrein-kinin system (KKS). The effects of 20 PFASs
      and the related long-chain aliphatic compounds were screened, and their binding
      affinities for the initial zymogen, Hagmen factor XII (FXII) in the KKS, were
      evaluated by molecular docking analysis. PFASs were demonstrated to activate the
      KKS in a structure-dependent mode. More specifically, PFASs with longer carbon
      chain length, higher fluorine atom substitution degree, and terminal acid group
      exhibited relatively higher activities in activating the KKS. The binding
      affinities of PFASs with FXII determined their capabilities for inducing KKS
      activation. The alternative binding modes of PFASs with FXII, together with van
      der Waals and hydrogen bonds, specifically accommodated the distinctive chemical
      structures. To our knowledge, PFASs, for the first time, were found to induce the
      activation of the KKS in plasma, and their chemical structure-related effects
      would be extremely important for risk assessment on emerging PFASs in addition to
      the listing in Stockholm Convention.

PMID- 28745507
TI  - Discovery of Potent Orally Active Protease-Activated Receptor 1 (PAR1)
      Antagonists Based on Andrographolide.
AB  - Protease-activated receptor-1 (PAR1), a G-protein-coupled receptor, plays a
      critical role in thrombin-mediated platelet aggregation. It is regarded as a
      promising antithrombosis target that is unlikely to result in bleeding. Here, we
      describe the synthesis of a series of novel PAR1 antagonists by borrowing the
      chiral fragment of andrographolide, an easily accessible natural molecule from
      Andrographis paniculata, to produce natural product/synthesis hybrids. An in
      vitro PAR1 inhibition assay and an in vivo pharmacokinetic profile led to the
      identification of compound 39 as the best PAR1 inhibitor. The further in vitro
      and ex vivo antiplatelet aggregation assays of compound 39 indicated that
      compound 39 was a potent antiplatelet agent. In addition, this compound is
      metabolically stable and displays a favorable pharmacokinetic profile with an
      elimination half-life of 3.1 h, which could be treated as a promising candidate
      for further clinical development.

PMID- 28745508
TI  - Assessment of Local Heterogeneity in Mechanical Properties of Nanostructured
      Hydrogel Networks.
AB  - Our current understanding of the mechanical properties of nanostructured
      biomaterials is rather limited to invasive/destructive and low-throughput
      techniques such as atomic force microscopy, optical tweezers, and shear rheology.
      In this report, we demonstrate the capabilities of recently developed dual
      Brillouin/Raman spectroscopy to interrogate the mechanical and chemical
      properties of nanostructured hydrogel networks. The results obtained from
      Brillouin spectroscopy show an excellent correlation with the conventional
      uniaxial and shear mechanical testing. Moreover, it is confirmed that, unlike the
      macroscopic conventional mechanical measurement techniques, Brillouin
      spectroscopy can provide the elasticity characteristic of biomaterials at a
      mesoscale length, which is remarkably important for understanding complex cell
      biomaterial interactions. The proposed technique experimentally demonstrated the
      capability of studying biomaterials in their natural environment and may
      facilitate future fabrication and inspection of biomaterials for various
      biomedical and biotechnological applications.

PMID- 28745509
TI  - Contact Angle and Adhesion Dynamics and Hysteresis on Molecularly Smooth
      Chemically Homogeneous Surfaces.
AB  - Measuring truly equilibrium adhesion energies or contact angles to obtain the
      thermodynamic values is experimentally difficult because it requires
      loading/unloading or advancing/receding boundaries to be measured at rates that
      can be slower than 1 nm/s. We have measured advancing-receding contact angles and
      loading-unloading adhesion energies for various systems and geometries involving
      molecularly smooth and chemically homogeneous surfaces moving at different but
      steady velocities in both directions, +/-V, focusing on the thermodynamic limit
      of +/-V -> 0. We have used the Bell Theory (1978) to derive expressions for the
      dynamic (velocity-dependent) adhesion energies and contact angles suitable for
      both (i) dynamic adhesion measurements using the classic Johnson-Kendall-Roberts
      (JKR, 1971) theory of "contact mechanics" and (ii) dynamic contact angle
      hysteresis measurements of both rolling droplets and syringe-controlled (sessile)
      droplets on various surfaces. We present our results for systems that exhibited
      both steady and varying velocities from V ~ 10 mm/s to 1 nm/s, where in all cases
      but one, the advancing (V > 0) and receding (V < 0) adhesion energies and/or
      contact angles converged toward the same theoretical (thermodynamic) values as V 
      > 0. Our equations for the dynamic contact angles are similar to the classic
      equations of Blake & Haynes (1969) and fitted the experimental adhesion data
      equally well over the range of velocities studied, although with somewhat
      different fitting parameters for the characteristic molecular length/dimension or
      area and characteristic bond formation/rupture lifetime or velocity. Our
      theoretical and experimental methods and results unify previous kinetic theories
      of adhesion and contact angle hysteresis and offer new experimental methods for
      testing kinetic models in the thermodynamic, quasi-static, limit. Our analyses
      are limited to kinetic effects only, and we conclude that hydrodynamic, i.e.,
      viscous, and inertial effects do not play a role at the interfacial velocities of
      our experiments, i.e., V < (1-10) mm/s (for water and hexadecane, but for viscous
      polymers it may be different), consistent with previously reported studies.

PMID- 28745510
TI  - Statistical Models for the Analysis of Isobaric Tags Multiplexed Quantitative
      Proteomics.
AB  - Mass spectrometry is being used to identify protein biomarkers that can
      facilitate development of drug treatment. Mass spectrometry-based labeling
      proteomic experiments result in complex proteomic data that is hierarchical in
      nature often with small sample size studies. The generalized linear model (GLM)
      is the most popular approach in proteomics to compare protein abundances between
      groups. However, GLM does not address all the complexities of proteomics data
      such as repeated measures and variance heterogeneity. Linear models for
      microarray data (LIMMA) and mixed models are two approaches that can address some
      of these data complexities to provide better statistical estimates. We compared
      these three statistical models (GLM, LIMMA, and mixed models) under two different
      normalization approaches (quantile normalization and median sweeping) to
      demonstrate when each approach is the best for tagged proteins. We evaluated
      these methods using a spiked-in data set of known protein abundances, a systemic
      lupus erythematosus (SLE) data set, and simulated data from multiplexed labeling
      experiments that use tandem mass tags (TMT). Data are available via
      ProteomeXchange with identifier PXD005486. We found median sweeping to be a
      preferred approach of data normalization, and with this normalization approach
      there was overlap with findings across all methods with GLM being a subset of
      mixed models. The conclusion is that the mixed model had the best type I error
      with median sweeping, whereas LIMMA had the better overall statistical properties
      regardless of normalization approaches.

PMID- 28745511
TI  - Stress-Induced Cubic-to-Hexagonal Phase Transformation in Perovskite Nanothin
      Films.
AB  - The strong coupling between crystal structure and mechanical deformation can
      stabilize low-symmetry phases from high-symmetry phases or induce novel phase
      transformation in oxide thin films. Stress-induced structural phase
      transformation in oxide thin films has drawn more and more attention due to its
      significant influence on the functionalities of the materials. Here, we
      discovered experimentally a novel stress-induced cubic-to-hexagonal phase
      transformation in the perovskite nanothin films of barium titanate (BaTiO3) with
      a special thermomechanical treatment (TMT), where BaTiO3 nanothin films under
      various stresses are annealed at temperature of 575  degrees C. Both high
      resolution transmission electron microscopy and Raman spectroscopy show a higher
      density of hexagonal phase in the perovskite thin film under higher tensile
      stress. Both X-ray photoelectron spectroscopy and electron energy loss
      spectroscopy does not detect any change in the valence state of Ti atoms, thereby
      excluding the mechanism of oxygen vacancy induced cubic-to-hexagonal (c-to-h)
      phase transformation. First-principles calculations show that the c-to-h phase
      transformation can be completed by lattice shear at elevated temperature, which
      is consistent with the experimental observation. The applied bending plus the
      residual tensile stress produces shear stress in the nanothin film. The thermal
      energy at the elevated temperature assists the shear stress to overcome the
      energy barriers during the c-to-h phase transformation. The stress-induced phase
      transformation in perovskite nanothin films with TMT provides materials
      scientists and engineers a novel approach to tailor nano/microstructures and
      properties of ferroelectric materials.

PMID- 28745512
TI  - Speed Limit for Triplet-Exciton Transfer in Solid-State PbS Nanocrystal
      Sensitized Photon Upconversion.
AB  - Hybrid interfaces combining inorganic and organic materials underpin the
      operation of many optoelectronic and photocatalytic systems and allow for
      innovative approaches to photon up- and down-conversion. However, the mechanism
      of exchange-mediated energy transfer of spin-triplet excitons across these
      interfaces remains obscure, particularly when both the macroscopic donor and
      acceptor are composed of many separately interacting nanoscopic moieties. Here,
      we study the transfer of excitons from colloidal lead sulfide (PbS) nanocrystals
      to the spin-triplet state of rubrene molecules. By reducing the length of the
      carboxylic acid ligands on the nanocrystal surface from 18 to 4 carbon atoms,
      thinning the effective ligand shell from 13 to 6 A, we are able to increase the
      characteristic transfer rate by an order of magnitude. However, we observe that
      the energy transfer rate asymptotes for shorter separation distances (<=10 A)
      which we attribute to the reduced Dexter coupling brought on by the increased
      effective dielectric constant of these solid-state devices when the aliphatic
      ligands are short. This implies that the shortest ligands, which hinder long-term
      colloidal stability, offer little advantage for energy transfer. Indeed, we find
      that hexanoic acid ligands are already sufficient for near-unity transfer
      efficiency. Using nanocrystals with these optimal-length ligands in an improved
      solid-state device structure, we obtain an upconversion efficiency of (7 +/- 1)%
      with excitation at lambda = 808 nm.

PMID- 28745513
TI  - Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products.
AB  - Serotonin (5-HT) receptors are important in health and disease, but the existence
      of 14 subtypes necessitates selective ligands. Previously, the pulicatins were
      identified as ligands that specifically bound to the subtype 5-HT2B in the 500 nM
      to 10 MUM range and that exhibited in vitro effects on cultured mouse neurons.
      Here, we examined the structure-activity relationship of 30 synthetic and natural
      pulicatin derivatives using binding, receptor functionality, and in vivo assays.
      The results reveal the 2-arylthiazoline scaffold as a tunable serotonin receptor
      targeting pharmacophore. Tests in mice show potential antiseizure and
      antinociceptive activities at high doses without motor impairment.

PMID- 28745514
TI  - Bitumen Emulsion Destabilization Kinetics: Importance of the Crystallized Wax
      Content.
AB  - We study the kinetics of bitumen emulsion destabilization after the addition of
      sodium hydroxide (NaOH) using macroscopic observations and rheology.
      Destabilization occurs in a two-step process: first, emulsion flocculates,
      forming a percolated network of contacting drops, and then coalescence provokes
      the irreversible connection of bitumen drops, leading to a bitumen continuous
      network that further relaxes the shape. We show that the destabilization kinetics
      exhibits a rheological easily identifiable signature allowing reproducible and
      accurate measurement of the connection/coalescence time trc (which corresponds to
      the time, determined by rheology, required to form the network made of drops
      connected by nonrelaxed coalescence). Using this powerful tool, we show that,
      even if viscosity is thought to govern the shape relaxation of the connected
      network it does not determine the connection kinetics. Indeed, emulsions with
      similar rheological behaviors exhibit very different destabilization times.
      Instead, we evidence a good correlation between the bitumen crystallized wax
      content and trc. From these experimental results, we discuss the stabilizing
      effect against coalescence of crystals in bitumen emulsions.

PMID- 28745515
TI  - Hydrology of the North Klondike River: carbon export, water balance and inter
      annual climate influences within a sub-alpine permafrost catchment.
AB  - Arctic and sub-arctic watersheds are undergoing significant changes due to recent
      climate warming and degrading permafrost, engendering enhanced monitoring of
      arctic rivers. Smaller catchments provide understanding of discharge, solute flux
      and groundwater recharge at the process level that contributes to an
      understanding of how larger arctic watersheds are responding to climate change.
      The North Klondike River, located in west central Yukon, is a sub-alpine
      permafrost catchment, which maintains an active hydrological monitoring station
      with a record of >40 years. In addition to being able to monitor intra-annual
      variability, this data set allows for more complex analysis of streamflow
      records. Streamflow data, geochemistry and stable isotope data for 2014 show a
      groundwater-dominated system, predominantly recharged during periods of snowmelt.
      Radiocarbon is shown to be a valuable tracer of soil zone recharge processes and
      carbon sources. Winter groundwater baseflow contributes 20 % of total annual
      discharge, and accounts for up to 50 % of total river discharge during the spring
      and summer months. Although total stream discharge remains unchanged, mean annual
      groundwater baseflow has increased over the 40-year monitoring period. Wavelet
      analysis reveals a catchment that responds to El Nino and longer solar cycles, as
      well as climatic shifts such as the Pacific Decadal Oscillation. Dedicated to
      Professor Peter Fritz on the occasion of his 80th birthday.

PMID- 28745516
TI  - Antibiotic stewardship from toolkit to local implementation: the 'gutta cavat
      lapidem' strategy.

PMID- 28745517
TI  - It is all about location: how to pinpoint microorganisms and their functions in
      multispecies biofilms.
AB  - Multispecies biofilms represent the dominant mode of life for the vast majority
      of microorganisms. Bacterial spatial localization in such biostructures governs
      ecological interactions between different populations and triggers the overall
      community functions. Here, we discuss the pros and cons of fluorescence-based
      techniques used to decipher bacterial species patterns in biofilms at single cell
      level, including fluorescence in situ hybridization and the use of genetically
      modified bacteria that express fluorescent proteins, reporting the significant
      improvements of those techniques. The development of tools for spatial and
      temporal study of multispecies biofilms will allow live imaging and spatial
      localization of cells in naturally occurring biofilms coupled with metabolic
      information, increasing insight of microbial community and the relation between
      its structure and functions.

PMID- 28745518
TI  - A Qualitative Study of How Preschoolers' Problematic Sleep Impacts Mothers.
AB  - BACKGROUND: Sleep disturbances are common among preschool-aged children. As
      children's problematic sleep is commonly defined by subjective reports from
      parents as to how the issue affects them, we took a qualitative approach to
      explore the perceptions and experiences of mothers and main caregivers of
      preschoolers with problematic sleep. The aim was to understand their firsthand
      experiences. METHODS: Purposive sampling was used to identify mothers of 3- to 4
      year-olds whose sleep was a problem for them. Semistructured interviews were
      conducted with 16 mothers. The interviews were analyzed for anticipated and
      emergent themes, the latter generated from exploring the impact of the child's
      sleep problems on the mother herself. RESULTS: Mothers described difficulties
      mainly with bedtime resistance and night waking and the adverse consequences
      affecting siblings and partners. Predominant themes falling under the umbrella of
      emotional responses (e.g., resignation, guilt or shame, confusion or frustration,
      and defeat) and daytime functioning (e.g., exhaustion, moodiness, poorer
      concentration, less socializing) emerged from mothers describing the impact the
      child's sleep problem had on her personally. CONCLUSIONS: This study highlights
      the overwhelming impact a child's sleep problems can have on a mother both
      emotionally and physically, and expressions of shame and guilt suggest some
      mothers assume much of the responsibility for their child's sleep problem. The
      findings provide insight into understanding mothers' personal responses in
      dealing with their preschoolers' sleep that could be useful to assist health
      professionals in history taking and establishing a treatment plan.

PMID- 28745519
TI  - An optimized protocol for anthraquinones isolation from Rhamnus frangula L.
AB  - Different from works described in the literature, which use expansive analytical
      methods to separation of anthraquinones derivatives (AQs), this communication
      reported a simple and inexpensive methodology to get them. In this way, the
      expensive commercial AQs: Chrysophanol, physcione and emodine were extracted from
      plant material (Rhamnus frangula L.) and isolated by classical column
      chromatography technique under optimised binary mobile phase gradients (CHCl3 :
      AcOEt(a), a = 1 to 5%) in excellent yields.

PMID- 28745520
TI  - Effects of Cognitive Behavioral Therapy for Insomnia on Sleep-Related Cognitions
      Among Patients With Stable Heart Failure.
AB  - OBJECTIVE/BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) improves
      insomnia and fatigue among chronic heart failure (HF) patients, but the extent to
      which sleep-related cognitions explain CBT-I outcomes in these patients is
      unknown. We examined the effects of CBT-I on sleep-related cognitions,
      associations between changes in sleep-related cognitions and changes in sleep and
      symptoms after CBT-I, and the extent to which cognitions mediated the effects of
      CBT-I. PARTICIPANTS: Stable New York Heart Association Class II-III HF patients
      (total n = 51; n = 26 or 51.0% women; M age = 59.1 +/- 15.1 years). METHODS: HF
      patients were randomized in groups to group CBT-I (n = 30) or attention control
      (HF self-management education, n = 21) and completed actigraphy, the Insomnia
      Severity Index, Pittsburgh Sleep Quality Index, Dysfunctional Beliefs and
      Attitudes about Sleep (DBAS) and Sleep Disturbance Questionnaires (SDQ), and self
      reported fatigue, depression, anxiety, and sleepiness (baseline, immediately
      after treatment, six months). We used mixed-effects modeling, mediation analysis
      with a bootstrapping approach, and Pearson correlations. RESULTS: There was a
      statistically significant group * mult time effect on DBAS. DBAS mediated the
      effects of CBT-I on insomnia severity and partially mediated CBT-I effects on
      fatigue. Improvements in dysfunctional cognitions were associated with improved
      sleep quality, insomnia severity, sleep latency and decreased fatigue,
      depression, and anxiety, with sustained effects at six months. CONCLUSIONS:
      Improvement in dysfunctional sleep-related cognitions is an important mechanism
      for CBT-I effects among HF patients who are especially vulnerable to poor sleep
      and high symptom burden.

PMID- 28745521
TI  - Dynamic value assessments in oncology supported by the PACE Continuous Innovation
      Indicators.
AB  - AIM: Several recently developed frameworks aim to assess the value of cancer
      treatments, but the most appropriate metrics remain uncertain. METHODS: We use
      data from the Patient Access to Cancer care Excellence Continuous Innovation
      Indicators to examine the relationship between hazard ratios (HRs) from clinical
      trials and dynamic therapeutic value accumulating over time. RESULTS: Our
      analysis shows that HRs from initial clinical trials poorly predict the eventual
      therapeutic value of cancer treatments. CONCLUSION: Relying strongly on HRs from
      registration trials to predict the long-term success of treatments leaves a lot
      of the variance unexplained. The Continuous Innovation Indicators offer a
      complementing, dynamic method to track the therapeutic value of cancer treatments
      and continuously update value assessments as additional evidence accumulates.

PMID- 28745522
TI  - Pharmacological characterization of the interaction between tiotropium and
      olodaterol administered at 5:5 concentration-ratio in equine bronchi.
AB  - Equine airways represent a suitable ex vivo model to study the functional impact
      of pharmacological treatments on human chronic obstructive pulmonary disorders,
      such as asthma and chronic obstructive pulmonary disease (COPD). We aimed to
      characterize the pharmacological interaction between the long-acting muscarinic
      antagonist (LAMA) tiotropium and the long-acting beta2-agonist (LABA) olodaterol
      in equine airways. The effect of tiotropium and olodaterol, administered alone
      and in combination at the ratio of concentrations reproducing ex vivo the
      concentration-ratio delivered by the currently available fixed-dose combination
      (FDC) (5:5), was investigated on the cholinergic contractile tone induced by the
      parasympathetic activation of equine isolated airways. The drug interaction was
      analysed by using the Bliss Independence and Unified Theory models. Both
      tiotropium and olodaterol induced a sub-maximal concentration-dependent
      inhibition of bronchial contractility (Emax: tiotropium 83.6 +/- 14.8%,
      olodaterol 76.9 +/- 17.9%; pEC50: tiotropium 8.2 +/- 0.5; olodaterol 8.3 +/-
      0.6). When administered at 5:5 concentration-ratio, tiotropium plus olodaterol
      completely inhibited the bronchial contractility (Emax 102.7 +/- 8.4%; pEC50 9.0
      +/- 0.7). Strong synergistic interaction was detected for tiotropium/olodaterol
      combination (combination index 0.011). When administered at low concentrations,
      the drug mixture elicited up to 94.6 +/- 9.5% effect that was 36.0 +/- 8.1%
      greater than the expected additive effect. The results of this study demonstrate
      that the co-administration of tiotropium plus olodaterol at 5:5 concentration
      ratio leads to synergistic inhibition of equine bronchial contractility when
      compared with either drug administered alone. These findings suggest that the
      currently available LABA/LABA FDC may be effective in delivering
      tiotropium/olodaterol combination at equipotency concentrations of each
      monocomponent into the lung and, thus, inducing synergistic effect in the
      airways.

PMID- 28745523
TI  - Affective Temperaments, Mood, and Insomnia Symptoms in a Nonclinical Sample.
AB  - OBJECTIVE: The aim of the study was to understand the relationship between
      affective temperaments and insomnia symptoms and to examine mood state as a
      mediator in this relationship. PARTICIPANTS: The sample consisted of 659 adults
      (428 women and 231 men), aged 18-77 years old, derived from a nonclinical
      population. METHODS: Affective temperaments were assessed using the Temperament
      Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A).
      Mood was measured using the UWIST Mood Adjective Checklist (UMACL). Insomnia was
      evaluated by the Athens Insomnia Scale. RESULTS: We found positive correlations
      among anxious, cyclothymic, depressive, and irritable affective temperaments and
      insomnia symptoms. Negative correlation with insomnia symptoms was found for
      hyperthymic temperament. Energetic arousal and tense arousal, as mood dimensions,
      positively correlated with insomnia symptoms. Hierarchical regression analysis
      indicated that anxious, cyclothymic, and hyperthymic temperaments were
      significant predictors of insomnia symptoms. Mediation analyses indicated that
      anxious, cyclothymic, and hyperthymic temperaments affected insomnia symptoms,
      both directly and indirectly, through energetic arousal as a mediator.
      CONCLUSIONS: The results showed a relationship between affective temperaments and
      insomnia symptoms and included the role of energetic arousal, a mood state
      dimension, as a mediator.

PMID- 28745524
TI  - Should Patients Switched from D to B in the GOLD 2017 Classification be
      Discontinued from Inhaled Corticosteroids?
AB  - Inhaled corticosteroids (ICSs) are the cornerstone of the treatment of asthma,
      but their role in COPD is limited. Several guidelines recommend their use in
      patients with severe airflow limitation, frequent exacerbations and asthma-COPD
      overlap (ACO), while the previous GOLD document recommended ICS for patients with
      high risk of exacerbations and a high level of symptoms (group D). Following the
      changes in the GOLD document 2017 update, in which impaired lung function is no
      longer considered as a determinant of exacerbation risk, a high number of COPD
      patients can now be labeled as group B (low risk of exacerbations and high level
      of symptoms) instead of D, and hence, no longer fulfill the indication for ICS.
      Since long-term therapy with ICS can entail secondary effects, the withdrawal of
      this treatment should be considered in this group of patients. In this article,
      we summarize the evidence for discontinuation of ICS in this subgroup of patients
      and provide suggestions for clinicians on the appropriate use on ICS in patients
      moving from D to B.

PMID- 28745525
TI  - Balance and Falls in Acute Exacerbation of Chronic Obstructive Pulmonary Disease:
      A Prospective Study.
AB  - Individuals with chronic obstructive pulmonary disease (COPD) have demonstrated
      balance impairment and a higher fall incidence. However, these have not been
      investigated in acute exacerbations of the disease (ECOPD). This study evaluates
      balance in patients during an ECOPD compared to stable COPD and healthy controls,
      and examines the fall incidence rate after hospitalisation due to ECOPD compared
      to individuals with stable COPD. Balance performance of 26 hospitalised patients
      with ECOPD was compared to 26 community-dwelling participants with stable COPD
      and 25 matched healthy controls. Balance was evaluated using computerised
      posturography and the Berg Balance Scale (BBS). Prospective falls were monitored
      by monthly calendars for 12 months in both COPD groups. Compared to controls,
      greater balance impairment was observed during ECOPD for most posturography
      variables across standing conditions (p <= 0.05). Both COPD groups had worse BBS
      scores (p <= 0.05) compared to controls. Increased dyspnoea and reduced
      quadriceps' strength were associated with impaired balance performance. A higher
      fall incidence (1.76 falls/person/year) was observed following hospitalisation in
      patients with ECOPD compared to stable COPD (0.53 falls/person/year) at 12
      months. Patients with ECOPD demonstrate balance impairments which are associated
      with increased dyspnoea and reduced muscle strength. Balance impairment during
      ECOPD may contribute to a high incidence of falls following hospitalisation.

PMID- 28745526
TI  - MMP-8 C-799T and MMP-8 C+17G polymorphisms in mild and severe preeclampsia:
      Association between MMP-8 C-799T with susceptibility to severe preeclampsia.
AB  - OBJECTIVE: The aim of present study was to determine the role of matrix
      metalloproteinase-8 (MMP-8) C-799T (rs11225395) and C+17 (rs2155052)
      polymorphisms in susceptibility to preeclampsia. STUDY DESIGN: In a case-control
      study, 256 pregnant women including 152 women with preeclampsia (86 women with
      mild preeclampsia and 66 women with severe preeclampsia) and 104 women with
      normal pregnancy from Western Iran with Kurdish ethnic background were
      investigated for MMP-8 C-799T and C + 17G polymorphisms using polymerase chain
      reaction-restriction fragment length polymorphism method. RESULTS: Comparing the
      MMP-8 TT genotype with the combined genotype of CC+CT (recessive model) indicated
      a significantly higher frequency of the MMP-8 TT genotype (47%) in severe
      preeclamptic patients than that in healthy pregnant women (30.8%) that was
      associated with 1.99-fold increased risk of severe preeclampsia (95% CI = 1.05
      3.77, p = 0.034). The frequency of MMP-8 G allele was 27.3% in all preeclamptic
      patients compared to 30.2% in controls (p = 0.56). Also, no significant
      difference was detected comparing the frequency of G allele in mild (26.6%, p =
      0.46) and severe preeclamptic patients (28.4%, p = 0.75) with controls (30.2%).
      CONCLUSIONS: Our study demonstrated that the MMP-8 C-799T is associated with the
      risk of developing severe preeclampsia during pregnancy. However, the MMP-8 C +
      17G polymorphism might not be a risk factor for susceptibility to preeclampsia.

PMID- 28745527
TI  - Human Agency and Global Catastrophic Biorisks.

PMID- 28745528
TI  - Predicting One-year Mortality After a "First" Hospitalization for Chronic
      Obstructive Pulmonary Disease: An Eight-Variable Assessment Score Tool.
AB  - Several authors have studied predictors of outcomes following a hospitalization
      for chronic obstructive pulmonary disease (COPD); however, few have reported
      outcomes following a first hospitalization for COPD. The objective is to develop
      a predictive mortality risk model in patients surviving a first hospitalization
      for COPD. This is a retrospective cohort study using linked administrative and
      clinical data. The cohort included 1129 patients of 40-84 years, discharged alive
      from a hospitalization for COPD in a regional hospital (Sherbrooke, Canada)
      between 04/2006 and 03/2013 and to whom were prescribed at least two COPD drugs
      during their hospitalization. One-year mortality was analysed using logistic
      regression on a derivation sample and validated on a testing sample. In total,
      141 (12.5%) patients died within one year from discharge of their first
      hospitalization for COPD. Predictors were: older age (OR (95% CI): 1.055 (1.026
      1.085)), male sex (OR (95% CI): 1.474 (0.921-2.358)), having a severe COPD
      exacerbation (OR (95% CI): 2.548 (1.571-4.132)), higher hospital length of stay
      (OR (95% CI): 1.024 (0.996-1.053)), higher Charlson co-morbidity index (OR (95%
      CI): 1.262 (1.099-1.449)), being diagnosed of cancer (OR (95% CI): 2.928 (1.456
      5.885)), the number of prior all-cause hospitalizations (OR (95% CI): 1.323
      (1.097-1.595)), and a COPD duration exceeding 3 years (OR (95% CI): 1.710 (1.058
      2.763)). A simple clinical prognosis tool is proposed and shows good
      discrimination in both the derivation and validation cohorts (c-statistic >0.78).
      One over eight patients discharged alive from a first COPD hospitalization will
      die the following year. It is thus important to identify higher-risk patients in
      order to plan and manage appropriate treatment.

PMID- 28745529
TI  - Sleepiness and Behavioral Risk-Taking: Do Sleepy People Take More or Less Risk?
AB  - BACKGROUND: Although sleep loss has been implicated in risk-taking behavior, it
      is unclear how individuals' current propensity to fall asleep, known as
      sleepiness, influences risk-taking. Because sleepiness is not only driven by
      recent sleep but also by factors such as circadian rhythm and current
      stimulation, it may be an important contributor to risk-taking as it reflects the
      more immediate sleep-wake state. PARTICIPANTS: One hundred thirty participants
      were recruited from a large Midwestern U.S. university. METHODS: Participants
      completed a short personality survey, reported their current sleepiness on the
      Stanford Sleepiness Scale, and then completed the Balloon Analog Risk Task, a
      computerized risk-taking measure in which participants earned real money for
      their performance. RESULTS: There was little support for a linear relation
      between sleepiness and risk-taking, but the evidence indicated a robust
      curvilinear relation. Even after controlling for important individual differences
      in sleep and risk-taking, participants who were moderately sleepy took longer to
      complete the risk-taking task, pumped balloons more, and exploded more balloons
      than those who were either low or high on sleepiness. CONCLUSIONS: The
      curvilinear relation between sleepiness and risk-taking sheds light on
      inconsistencies in prior findings linking sleepiness and sleep loss to risk
      taking behavior. Moreover, current sleepiness appears to have unique implications
      for risk-taking.

PMID- 28745530
TI  - Agomelatine-based in situ gels for brain targeting via the nasal route:
      statistical optimization, in vitro, and in vivo evaluation.
AB  - Agomelatine (AGM) is an antidepressant drug with a low absolute bioavailability
      due to the hepatic first pass metabolism. AGM-loaded solid lipid nanoparticles
      were formulated in the form of an in situ gel to prolong the intranasal retention
      time and subsequently to increase the absorbed amount of AGM. The optimized in
      situ gel formula had a sol-gel transition temperature of 31  degrees C +/- 1.40,
      mucociliary transport time of 27 min +/-1.41%, released after 1 and 8 h of 46.3%
      +/- 0.85 and 70.90% +/- 1.48. The pharmacokinetic study of the optimized in situ
      gel revealed a significant increase in the peak plasma concentration, area under
      plasma concentration versus time curve and absolute bioavailability compared to
      that of the oral suspension of Valdoxan(r) with the values of 247 +/- 64.40
      ng/mL, 6677.41 +/- 1996 ng.min/mL, and 37.89%, respectively. It also gave drug
      targeting efficiency index of 141.42 which revealed more successful brain
      targeting by the intranasal route compared to the intravenous route and it had
      direct transport percent index of 29.29 which indicated a significant
      contribution of the direct nose to brain pathway in the brain drug delivery.

PMID- 28745531
TI  - Risk of underdiagnosis of hypertension in schizophrenia patients.
AB  - AIM: Arterial hypertension requires proper screening and management, and its
      underdiagnosis in patients with schizophrenia (SZ) and/or antipsychotic treatment
      has been postulated. The objective of the study is to assess whether there are
      differences in the proportion of screened patients with a blood pressure >140/90
      mmHg that are undiagnosed or not confirmed later (risk of underdiagnosis).
      METHODS: Cross-sectional study of clinical records from SIDIAPQ (Spain) during
      the 2006-2011 period. Three groups were studied: SZ, no SZ but under
      antipsychotic treatment, and control groups. Patients with established
      hypertension, cardiovascular disease, dementia, or diagnosis of SZ or starting
      with antipsychotic treatment during this period were excluded. RESULTS: The SZ
      group had a lower risk of underdiagnosis than the control group (OR 0.91; 95% CI:
      0.83-0.99; p < 0.05), at the expense of men (OR 0.8; 95% CI: 0.71-0.9; p < 0.001)
      and patients younger than 50 years of age (OR: 0.84; 95% CI: 0.74-0.93; p <
      0.003). In the no SZ but under antipsychotic treatment group there were some
      differences, but not in the overall results. CONCLUSION: Preventive management of
      hypertension seemed to be sufficient for SZ and antipsychotic treatment patients.
      The lower prevalence of hypertension found in these groups may be due to other
      factors (blood pressure-lowering effect of psychoactive drugs or smoking) but
      these hypotheses must be evaluated with specific studies.

PMID- 28745532
TI  - Regulatory T-Cell Distribution within Lung Compartments in COPD.
AB  - The importance of the adaptive immune response, specifically the role of
      regulatory T (Treg) cells in controlling the obstruction progression in smokers,
      has been highlighted. To quantify the adaptive immune cells in different lung
      compartments, we used lung tissues from 21 never-smokers without lung disease, 22
      current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex
      smokers with chronic obstructive pulmonary disease (COPD) for histological
      analysis. We observed increased T, B, IL-17 and BAFF+ cells in small and large
      airways of COPD individuals; however, in the NOS, we only observed increase in T
      and IL-17+ cells only in small airways. A decrease in the density of Treg+, TGF
      beta+ and IL-10+ in small and large airways was observed only in COPD
      individuals. In the lymphoid tissues, Treg, T,B-cells and BAFF+ cells were also
      increased in COPD; however, changes in Treg inhibitory associated cytokines were
      not observed in this compartment. Therefore, our results suggest that difference
      in Treg+ cell distributions in lung compartments and the decrease in TGF-beta+
      and IL-10+ cells in the airways may lead to the obstruction in smokers.

PMID- 28745533
TI  - Anterior discectomy could still be an alternative to corpectomy in highly
      migrated cervical disc herniation.
AB  - OBJECTIVE: For cases of cervical disc herniation, highly migrated cervical disc
      (HMCD) is clinically rare and usually treated with anterior cervical corpectomy
      and fusion (ACCF). This study aims to analyze the feasibility of anterior
      cervical discectomy and fusion (ACDF) for the patients with HMCD. METHOD:
      Clinical data of 32 patients with HMCD treated with ACDF or ACCF were
      retrospectively reviewed. Migration distances of the disc prolapses were
      measured. The mJOA score was used to evaluate surgical effect. RESULTS: ACDF was
      successful in 27 patients while ACCF was used for the remaining 5 because of
      epidural disc prolapse adhesion or unreachable migrated fragments. Complete
      spinal cord decompression without residual disc fragments was observed in
      postoperative MRI of all cases. The mean migration distance of the disc prolapses
      in ACDF group was 7.3 mm, comparing to 11.4 mm in ACCF group. No disc prolapse in
      ACDF group exceeded the axial length of the vertebral bodies while three of five
      in ACCF group did. Preoperative mean mJOA scores in ACDF group and ACCF group
      were 8.20 +/- 2.75 and 6.10 +/- 2.15, respectively. Postoperative mean mJOA
      scores in those two groups were significantly improved to 14.70 +/- 1.55 (p <
      .001) and 12.80 +/- 1.72 (p < .001), with an improvement rate of 72.80 +/- 4.76%
      and 62.90 +/- 9.46%, respectively. CONCLUSION: ACDF is feasible for patients with
      HMCD except for cases of epidural disc prolapse adhesion or huge disc prolapse
      which migrates over the axial length of the vertebral body. Clinical symptoms can
      be significantly improved with few serious complications in those patients
      including ones underwent alternative ACCF due to a failed ACDF.

PMID- 28745534
TI  - Reply: A dynamic approach for outpatient scheduling.

PMID- 28745535
TI  - Re: Saint-Laurent Thibault C, Moorjaney D, Ganz ML, et al. Cost-effectiveness of
      combination daclatasvir-sofosbuvir for treatment of genotype 3 chronic hepatitis
      C infection in the United States. J Med Econ 2017;20:692-702.

PMID- 28745536
TI  - Reply: Cost-effectiveness of combination daclatasvir-sofosbuvir for treatment of
      genotype 3 chronic hepatitis C infection in the United States.

PMID- 28745537
TI  - Spatial genetic structure and body size divergence in endangered Gymnogobius
      isaza in ancient Lake Biwa.
AB  - Gymnogobius isaza is a freshwater goby endemic to ancient Lake Biwa, the largest
      lake in Japan. The species is now listed as 'Critically Endangered' in the Red
      Data Book of Japan. Nevertheless, it remains subject to fishing without any
      specific management strategies. Previous studies using mitochondrial DNA markers
      showed that this fish species has two cryptic lineages. However, little is known
      about spatial genetic structure and ecological differences across the broad
      lakescape. In this study, we collected fish samples at nine locations along the
      lakeshore during the breeding season and tested for the presence of spatial
      heterogeneity in the lineage's composition while measuring body size as the most
      fundamental biological trait. The results showed that the major lineage dominated
      all the sampling locations whereas the minor lineage consisted of only 11%
      (16/143) of samples. Furthermore, although their spatial distributions overlapped
      (i.e. the two lineages may be well mixed), we found it possible that the minor
      lineage may have a potentially narrower distribution than the major lineage. In
      addition, we found that the two lineages differ in body size; specifically, the
      minor lineage is smaller in size. From the viewpoint of genetic diversity
      conservation and sustainable resource use, this fish should be managed as two
      genetic stocks and spatial and/or body size-based fishery management is
      desirable, with particular attention to the minor (smaller sized) lineage.

PMID- 28745538
TI  - Sinorhizobium meliloti Chemotaxis to Multiple Amino Acids Is Mediated by the
      Chemoreceptor McpU.
AB  - The legume symbiont Sinorhizobium meliloti is chemoattracted to compounds exuded
      by germinating seeds of its host alfalfa. This response is mainly mediated by the
      S. meliloti chemoreceptor McpU. McpU also has a prominent contribution in sensing
      a synthetic amino acid (aa) mixture mimicking the amounts and composition
      observed in seed exudate. Here, we used the hydrogel capillary assay to quantify
      chemotactic responses of S. meliloti to individual aa exuded by germinating
      alfalfa seeds and to define the role of McpU in this behavior. S. meliloti
      exhibited positive chemotaxis responses to all proteinogenic aa, except for
      aspartate, and to citrulline, cystine, gamma-aminobutyric acid, and ornithine.
      Wild-type responses were diverse in intensity, while a strain lacking mcpU
      displayed strongly diminished responses. Differential scanning fluorimetry
      demonstrated interaction of the purified periplasmic region of McpU (McpU-PR)
      with the aa, except glutamate and aspartate. We additionally tested organic acids
      and sugars, but there were no significant interactions with the McpU ligand
      binding domain, except for citrate. Using ligand displacement, we confirmed the
      interaction of McpU-PR with aa representing strong and weak attractants. Our
      results show that S. meliloti McpU is a broad-range aa receptor mediating
      differential responses to individual attractants, which does not bind negatively
      charged aa.

PMID- 28745539
TI  - Congenital heart disease and genetic syndromes: new insights into molecular
      mechanisms.
AB  - INTRODUCTION: Advances in genetics allowed a better definition of the role of
      specific genetic background in the etiology of syndromic congenital heart defects
      (CHDs). The identification of a number of disease genes responsible for different
      syndromes have led to the identification of several transcriptional regulators
      and signaling transducers and modulators that are critical for heart
      morphogenesis. Understanding the genetic background of syndromic CHDs allowed a
      better characterization of the genetic basis of non-syndromic CHDs. In this
      sense, the well-known association of typical CHDs in Down syndrome, 22q11.2
      microdeletion and Noonan syndrome represent paradigms as chromosomal aneuploidy,
      chromosomal microdeletion and intragenic mutation, respectively. Area covered:
      For each syndrome the anatomical features, distinctive cardiac phenotype and
      molecular mechanisms are discussed. Moreover, the authors include recent genetic
      findings that may shed light on some aspects of still unclear molecular
      mechanisms of these syndromes. Expert commentary: Further investigations are
      needed to enhance the translational approach in the field of genetics of CHDs.
      When there is a well-established definition of genotype-phenotype (reverse
      medicine) and genotype-prognosis (predictive and personalized medicine)
      correlations, hopefully preventive medicine will make its way in this field.
      Subsequently a reduction will be achieved in the morbidity and mortality of
      children with CHDs.

PMID- 28745540
TI  - p53 and Mdm2 act synergistically to maintain cardiac homeostasis and mediate
      cardiomyocyte cell cycle arrest through a network of microRNAs.
AB  - Defining the roadblocks responsible for cell cycle arrest in adult cardiomyocytes
      lies at the core of developing cardiac regenerative therapies. p53 and Mdm2 are
      crucial mediators of cell cycle arrest in proliferative cell types, however,
      little is known about their function in regulating homeostasis and proliferation
      in terminally differentiated cell types, like cardiomyocytes. To explore this, we
      generated a cardiac-specific conditional deletion of p53 and Mdm2 (DKO) in adult
      mice. Herein we describe the development of a dilated cardiomyopathy, in the
      absence of cardiac hypertrophy. In addition, DKO hearts exhibited a significant
      increase in cardiomyocyte proliferation. Further evaluation showed that
      proliferation was mediated by a significant increase in Cdk2 and cyclin E with
      downregulation of p21Cip1 and p27Kip1. Comparison of miRNA expression profiles
      from DKO mouse hearts and controls revealed 11 miRNAs that were downregulated in
      the DKO hearts and enriched for mRNA targets involved in cell cycle regulation.
      Knockdown of these miRNAs in neonatal rat cardiomyocytes significantly increased
      cytokinesis with an upregulation in the expression of crucial cell cycle
      regulators. These results illustrate the importance of the cooperative activities
      of p53 and Mdm2 in a network of miRNAs that function to impose a barrier against
      aberrant cardiomyocyte cell cycle re-entry to maintain cardiac homeostasis.

PMID- 28745541
TI  - Chaperone proteins as single component reagents to assess antibody
      nonspecificity.
AB  - Early stage assays that evaluate monoclonal antibody drug-like properties serve
      as valuable tools for selection of lead candidates. One liability for clinical
      development, off-target reactivity, is often assessed by binding to a mixture or
      panel of noncognate proteins. While robust, these mixes are often ill-defined,
      and can suffer from issues such as lot-to-lot variability. In this study, we
      discovered in immunoprecipitation experiments that certain chaperones are present
      in one of these mixtures;we then explored the use of recombinant chaperone
      proteins as well-characterized agents to predict antibody nonspecificity.
      Antibody binding to the heat shock proteins HSP70, HSP90, or trigger factor all
      served as predictors of cross-interaction propensity, with HSP90 providing the
      greatest ability to predict antibody clearance rates in mouse. Individual
      chaperone binding correlates surprisingly closely with binding to complex cell
      extracts, with the exception of a few "false negatives" (assuming a complex cell
      extract as the "true" value). As defined reagents, these chaperone reagents
      present advantages for high throughput assays of nonspecificity.

PMID- 28745542
TI  - The 4D nucleome in Krakow - Prospects for an emerging field.
AB  - asbtract It may seem obvious that the structural complexity of the cell nucleus
      should be investigated by microscopy methods. However, the researchers' toolbox
      has been enriched enormously in recent years by ideas arriving from a number of
      fields unrelated to microscopy. The recent conference 4D Nucleome: The Cell
      Nucleus in Space and Time, which was held in Krakow in May 2017, was an
      opportunity to appreciate the growing number of conceptual approaches and newly
      emerging analytical techniques that are revolutionizing our understanding of the
      structure of chromatin and the nucleus.

PMID- 28745543
TI  - Enhanced adhesion of blood platelets to intact endothelium of mesenteric vascular
      bed in mice with streptozotocin-induced diabetes is mediated by an up-regulated
      endothelial surface deposition of VWF - In vivo study.
AB  - Numerous in vitro experiments have confirmed that a dysfunctional endothelium is
      characterized by, inter alia, a higher affinity for binding of platelets and
      leukocytes. However, there is still no direct evidence for greater interaction
      between platelets and intact endothelium in in vivo animal models of diabetes.
      Therefore, the present study examines the pro-adhesive properties of endothelium
      change in vivo as an effect of streptozotocin (STZ)-induced diabetes and the role
      of two key platelet receptors: GPIb-IX-V and GPIIb/IIIa. Mice of C57BL strain
      with streptozotocin-induced diabetes were used in the study. Flow cytometry was
      used to assess basal activation and reactivity of platelets. Adhesion of
      platelets to the vascular wall was visualized with the use of intravital
      microscopy in mesentery. The contribution of GPIIb/IIIa and GPIb-IX-V was
      evaluated by the injection of Fab fragments of respective antibodies. The
      integrity of the endothelium and vWf expression were evaluated histochemically.
      Basal activation and reactivity of platelets in streptozotocin-diabetic mice were
      elevated. Blood platelets adhered more often to the vascular wall of diabetic
      mice than nondiabetic animals: 11.9 (6.4; 32.8) plt/min/mm2 (median [IQR]) vs 2.7
      (1.3; 6.4) plt/min/mm2. The injection of anti-GPIbalpha antibodies decreased the
      number of adhering platelets from 89.5 (34.0; 113.1) plt/min/mm2 (median [IQR])
      in mice treated with isotype antibodies to 3.1 (1.7; 5.6) plt/min/mm2 in mice
      treated with blocking antibodies. The effect of GPIIb/IIIa blockage was not
      significant. Immunohistochemistry revealed a higher expression of vWF in the
      endothelium of STZ mice, but no substantial changes in endothelial morphology
      were detected. To conclude, the study shows that the platelets interact more
      frequently with the mesenteric vascular bed in mice with 1-month STZ-induced
      diabetes than in healthy mice. These interactions are mediated via platelet GPIb
      IX-V and are driven by increased expression of vWF in endothelial cells.

PMID- 28745545
TI  - A link between very long chain fatty acid elongation and mating-specific yeast
      cell cycle arrest.
AB  - Ceramides and sphingolipid intermediates are well-established regulators of the
      cell cycle. In the budding yeast Saccharomyces cerevisae, the complex
      sphingolipid backbone, ceramide, comprises a long chain sphingoid base, a polar
      head group, and a very long chain fatty acid (VLCFA). While ceramides and long
      chain bases have been extensively studied as to their roles in regulating cell
      cycle arrest under multiple conditions, the roles of VLCFAs are not well
      understood. Here, we used the yeast elo2 and elo3 mutants, which are unable to
      elongate fatty acids, as tools to explore if maintaining VLCFA elongation is
      necessary for cell cycle arrest in response to yeast mating. We found that both
      elo2 and elo3 cells had severely reduced mating efficiencies and were unable to
      form polarized shmoo projections that are necessary for cell-cell contact during
      mating. They also lacked functional MAP kinase signaling activity and were
      defective in initiating a cell cycle arrest in response to pheromone. Additional
      data suggests that mislocalization of the Ste5 scaffold in elo2 and elo3 mutants
      upon mating initiation may be responsible for the inability to initiate a cell
      cycle arrest. Moreover, the lack of proper Ste5 localization may be caused by the
      inability of mutant cells to mobilize PIP2. We suggest that VLCFAs are required
      for Ste5 localization, which is a necessary event for initiating MAP kinase
      signaling and cell cycle arrest during yeast mating initiation.

PMID- 28745544
TI  - Euptox A Induces G1 Arrest and Autophagy via p38 MAPK- and PI3K/Akt/mTOR-Mediated
      Pathways in Mouse Splenocytes.
AB  - Euptox A (9-oxo-10, 11-dehydroageraphorone), the main toxin isolated from
      Eupatorium adenophorum, is known to induce immunotoxicity in animals. However,
      the precise mechanism underlying the effects of Euptox A on splenocytes is
      unclear. Here, we aimed to investigate the molecular mechanisms underlying the
      effect of Euptox A in mouse spleens after its intragastric administration and
      found that Euptox A exhibits proautophagic effects in splenocytes. Euptox A
      markedly arrested the splenocytes in the G0/G1 phase, which was accompanied by
      inhibition of the expression of the positive regulators CDK4, CDK2, cyclin D1,
      PCNA, and E2F1, and promotion of the expression of the negative regulators p53,
      p21 Waf1/Cip1, p27 Kip1, and Chk1. We also found that Euptox A did not markedly
      induce splenocyte apoptosis, but induced autophagy while increasing the
      subcellular localization of punctate LC3, ratio of LC3-II/LC3-I, and Beclin 1
      levels, and decreasing p62 levels. Euptox A also significantly inhibited p-PI3K,
      p-p38 MAPK, p-Akt, and p-mTOR expression, but increased PTEN and p-AMPK
      expression. These results indicated that Euptox A induced splenocyte autophagy by
      inhibiting the PI3K/Akt/mTOR pathway, suppressing p38 MAPK expression, and
      activating AMPK. These findings provide new insights into the mechanisms involved
      in spleen toxicity caused by Euptox A in mice.

PMID- 28745546
TI  - Using a Modified Bookmark Procedure to Help Identify Reasonable Consequences for
      Academic Integrity Violations.
AB  - It is recommended that institutions develop academic conduct policies to help
      preserve academic integrity, enforce compliance, and aid in legal defensibility.
      These policies should also articulate reasonable consequences for persons found
      in violation. The problem, however, is that all academic misconduct offenses are
      not created equal, and determining reasonable consequences for these violations
      can be particularly challenging due to their subjective nature. Thus, the purpose
      of this study was to introduce a novel method for more objectively determining
      reasonable sanctions for several academic misconduct offenses of varying degrees
      of severity. We utilized a variation of the Bookmark procedure, a popular
      standard-setting technique used primarily by psychometricians in high-stakes
      testing environments, to investigate empirical survey data and develop policy
      recommendations. We encourage others to use this procedure, where appropriate, to
      identify appropriate cut scores and ranges to aid in policy development across a
      variety of contexts.

PMID- 28745547
TI  - Pharmacogenetics may influence the impact of inflammation on voriconazole trough
      concentrations.
AB  - How pharmacogenetics modulates the inhibitory effects of inflammation on
      voriconazole trough concentration (Cmin) remains unknown. In 29 recipients of
      allogeneic hematopoietic stem cell transplantation retrospectively studied, both
      a genetic score (which aggregated CYP2C19 and CYP3A genotypes) and inflammation
      significantly influenced voriconazole Cmin (n = 260). A trend toward (p = 0.03) a
      greater impact of inflammation in patients with the highest genetic score
      (corresponding to ultra-rapid metabolizers) was observed. Further researches are
      needed to confirm these data.

PMID- 28745548
TI  - Toward Gender Equality in Outcomes After Percutaneous Coronary Intervention.

PMID- 28745550
TI  - Improvising 5-HT7R homology model for design of high affinity ligands: model
      validation with docking, embrace minimization, MM-GBSA, and molecular dynamic
      simulations.
AB  - The subtype, 5-HT7R has been implicated in neurological disorders and presents
      itself as a promising target for antidepressant drugs. Design of targeted
      selective ligands, require a sound knowledge of 3D-receptor structure. In absence
      of receptor structure, structure-based design of targeted ligands relies on
      generation of 5-HT7R homology model. In this study, the impact of template
      choice, alignment, and model building methods on the homology model of 5-HT7R is
      addressed. The compactness and model quality due to the presence of cholesterol
      (lipidic receptor) have also been observed. The results suggest good
      stereochemical quality of the final model. Ramachandran Plot Analysis indicated
      more than 97.5% amino acid residues in the favorable region. The overall quality
      factor was 91.8% using ERRAT. The Z-score for backbone confirmation and packing
      quality were -1.248 and -1.427, respectively, using WHATCHECK. The RMS Z-score
      for side chain planarity was .711. Other validation results for the final model
      include binding site analysis in which Asp162, Val163, Phe343, Phe344, Arg350,
      Arg367, and Leu370 conserved residues were found in the active site, correlation
      coefficient of .82 in ligand-based screening and .85 in embrace minimization.
      Further, the model showed good correlation for agonist and antagonist in docking
      ([Formula: see text] ~ .76, [Formula: see text] ~ .82), embrace minimization
      ([Formula: see text] ~ .73, [Formula: see text] ~ .72), and MM-GBSA ([Formula:
      see text] ~ .69, [Formula: see text] ~ .75) studies. The model was subjected to
      Molecular Dynamics (MD) simulation of 20 ns both in ligand-free and ligand-bound
      receptor (agonist and antagonist) system in order to assess its stability.

PMID- 28745549
TI  - Prior opioid exposure influences parents' sharing of their children's CYP2D6
      research results.
AB  - AIM: To determine parents' use of their children's CYP2D6 research result. We
      hypothesized that perceived utility, likelihood of sharing and actual sharing of
      results would differ between parents with children previously exposed (cases) or
      unexposed (controls) to opioids. METHODS: We returned results by phone
      (baseline). We surveyed parents about perceived utility and likelihood of sharing
      their child's research result at baseline, and actual sharing at 3 and 12 months.
      RESULTS: Cases were more likely than controls to agree that they (p = 0.022) and
      the doctors (p = 0.041) could use the results to care for their child, to report
      higher likelihood of sharing (p = 0.042) and to actually share results with the
      child's doctor (p = 0.026). CONCLUSION: Prior opioid exposure influenced
      perceived clinical utility and sharing behaviors.

PMID- 28745551
TI  - Institutional profile of pharmacogenetics within University of Michigan College
      of Pharmacy.
AB  - The University of Michigan College of Pharmacy has made substantial investment in
      the area of pharmacogenomics to further bolster its activity in pharmacogenomics
      research, implementation and education. Four tenure-track faculty members have
      active research programs that focus primarily on the discovery of functional
      polymorphisms (HJ Zhu), and genetic associations with treatment outcomes in
      patients with cancer (DL Hertz), cardiovascular disease (JA Luzum) and
      psychiatric conditions (VL Ellingrod). Recent investments from the University and
      the College have accelerated the implementation of pharmacogenetics broadly
      across the institution and in targeted therapeutic areas. Students within the
      PharmD and other health science professions receive substantial instruction in
      pharmacogenomics, in preparation for careers in biomedical health in which they
      can contribute to the generation, dissemination and utilization of
      pharmacogenomics knowledge to improve patient care.

PMID- 28745552
TI  - Human interaction with robotic systems: performance and workload evaluations.
AB  - We first tested the effect of differing tactile informational forms (i.e.
      directional cues vs. static cues vs. dynamic cues) on objective performance and
      perceived workload in a collaborative human-robot task. A second experiment
      evaluated the influence of task load and informational message type (i.e. single
      words vs. grouped phrases) on that same collaborative task. In both experiments,
      the relationship of personal characteristics (attentional control and spatial
      ability) to performance and workload was also measured. In addition to objective
      performance and self-report of cognitive load, we evaluated different
      physiological responses in each experiment. Results showed a performance-workload
      association for directional cues, message type and task load. EEG measures
      however, proved generally insensitive to such task load manipulations. Where
      significant EEG effects were observed, right hemisphere amplitude differences
      predominated, although unexpectedly these latter relationships were negative.
      Although EEG measures were partially associated with performance, they appear to
      possess limited utility as measures of workload in association with tactile
      displays. Practitioner Summary: As practitioners look to take advantage of
      innovative tactile displays in complex operational realms like human-robotic
      interaction, associated performance effects are mediated by cognitive workload.
      Despite some patterns of association, reliable reflections of operator state can
      be difficult to discern and employ as the number, complexity and sophistication
      of these respective measures themselves increase.

PMID- 28745553
TI  - The role of midgut symbiotic bacteria in resistance of Anopheles stephensi
      (Diptera: Culicidae) to organophosphate insecticides.
AB  - In the current study, the effects of the presence of symbiotic bacteria on the
      activity of the enzymes involved in An. stephensi resistance to temephos are
      evaluated for the first time. Four different strains (I. susceptible strain, II.
      resistant strain, III. resistant strain + antibiotic, and IV. resistant strain +
      bacteria) were considered in order to determine the possible effects of the
      symbiotic bacteria on their hosts' resistance to temephos. The median values of
      all enzymes of susceptible strain were compared with those of other resistant
      strains. The results of this study indicated a direct relationship between the
      presence of bacteria in the symbiotic organs of An. stephensi and resistance to
      temephos. The profile of enzymatic activities in the resistant strain changed to
      a susceptible status after adding antibiotic. The resistance of An. stephensi to
      temephos could be completely broken artificially by removing their bacterial
      symbionts in a resistant population.

PMID- 28745554
TI  - Anaplastic lymphoma kinase rearrangements in non-small-cell lung cancer: novel
      applications in diagnostics and treatment.
AB  - The ALK gene, first identified as an anaplastic large cell lymphoma driver
      mutation, is dysregulated in nearly 20 different human malignancies, including 3
      7% of non-small-cell lung cancers (NSCLC). In NSCLC, ALK commonly fuses with the
      EML4, forming a constitutively active tyrosine kinase that drives oncogenic
      progression. Recently, several ALK-inhibiting drugs have been developed that are
      more effective than standard chemotherapeutic regimens in treating advanced ALK
      positive NSCLC. For this reason, molecular diagnostic testing for dysregulated
      ALK expression is a necessary part of identifying optimal NSCLC treatment
      options. Here, we review the molecular pathology of ALK-positive NSCLC, ALK
      molecular diagnostic techniques, ALK-targeted NSCLC treatments, and drug
      resistance mechanisms to ALK-targeted therapies.

PMID- 28745555
TI  - The effect of rs5758550 on CYP2D6*2 phenotype and formation of endoxifen in
      breast cancer patients using tamoxifen.
AB  - AIM: CYP2D6*2 is considered fully active, but it has been suggested that it only
      happens in the presence of rs5758550. This study aims to elucidate the impact of
      this enhancer. MATERIALS & METHODS: DNA and blood samples from women enrolled in
      the CYPTAM study (NTR1509) were analyzed. Fourteen CYP2D6*2 carriers without the
      enhancer were reclassified. The relationship of CYP2D6 phenotypes and drug levels
      was studied. RESULTS: After correction for the absence of the enhancer, the
      correlation between CYP2D6 phenotypes and endoxifen did not improve (R2: 0.290 vs
      0.279). No difference was observed in mean concentrations between CYP2D6*2
      individuals with and without the enhancer. CONCLUSION: The rs5758550 enhancer
      does not lead to improved prediction of endoxifen levels in breast cancer
      patients.

PMID- 28745556
TI  - Gonorrhoea in Greenland, incidence and previous preventive measures: a review to
      improve future strategies.
AB  - Gonorrhoea continues to be a significant health challenge in Greenland. The aim
      of this study was to describe the development of gonorrhoea in Greenland through
      time including incidence rates and previous measures taken to address the
      challenge. A systematic literature search in PubMed, Embase and The Cochrane
      Library was conducted. Furthermore, local archives were searched in the Health
      Clinic in Nuuk for relevant literature. From the 1940s the incidence of
      gonorrhoea increased steadily with a steep incline around 1970, possibly as a
      consequence of changes in living conditions and urbanisation. Significant
      declines in the incidence were seen the late 1970s and again in the late 1980s,
      most likely in the wake of an outbreak of ulcus molle/chancroid in the 1970s and
      as a result of focused education in venereology for Greenlandic nurses in the
      late 1980s combined with the stop-AIDS campaign. Since the early 1990s the
      incidence of gonorrhoea in Greenland has not risen to previously high levels.
      However, the incidence remains high and with a gradually increasing trend.
      Prevention intervention strategies such as peer-to-peer sexual education,
      storytelling and involvement of parent/guardian in sexual education of the youth
      could be appropriate approaches to improve sexual health in Greenland.

PMID- 28745557
TI  - Building Capacity for Evidence-Based Practice Together.
AB  - Social workers are increasingly called to implement evidence-based practices and
      systematically evaluate efficacy. As healthcare reform magnifies these mandates
      for a growing population of service users, social work educators are positioned
      to play important roles in helping organizations build capacity for this work.
      This article presents two examples of faculty members successfully filling this
      role; one developed a teaching model for evidence-based practice that
      synchronized classroom and field continuing education, and the other linked
      curricular goals with an agency's need for program evaluation. The success of
      these initiatives identifies opportunities for educators to meet growing needs in
      health services.

PMID- 28745558
TI  - Considering the effects of ambient particulate matter on the lung function of
      motorcycle taxi drivers in Bangkok, Thailand.
AB  - : The motorcycle taxi drivers of Bangkok have been heavily exposed to high
      concentrations of PM10 (particulate matter with an aerodynamic diameter <=10
      MUm), and the impact of this on their lungs has been neither documented nor
      studied. This study examines the association between exposure to PM10 and lung
      function decline among motorcycle taxi drivers. A cross-sectional study was
      conducted in Bangkok between two groups: a subject group of motorcycle taxi
      drivers and control group of enclosed vehicle taxi drivers. The findings of the
      Thailand Pollution Control Department were used to estimate the annual ambient
      PM10 concentration levels in the metropolis. Pulmonary functions of motorcycle
      taxi drivers and enclosed vehicle taxi drivers were measured and compared using
      the Mann-Whitney test. Multiple linear regression analysis was applied to
      estimate the effects of PM10 exposure on the lung function of motorcycle taxi
      drivers. A total of 1283 motorcycle taxi drivers and 600 taxi drivers were
      investigated. The mean forced expiratory volume in 1 sec/forced vital capacity
      (FEV1/FVC) of the motorcycle taxi drivers was significantly lower than that of
      the taxi drivers (P < 0.001). The mean FEV1/FVC of motorcycle taxi drivers
      exposed to >=50 ug/m3 PM10 was statistically lower (-2.82%; 95% confidence
      interval [CI]: -4.54% to -1.09%) and the mean % vital capacity (%VC) of those
      exposed to 40-49.9 ug/m3 PM10 was statistically lower than that of motorcycle
      taxi drivers exposed to <30 ug/m3 PM10 (-3.33%; 95% CI: -5.79% to -0.87%).
      Motorcycle taxi drivers were directly exposed to air pollution in their working
      environment. As a result, their lung function might decrease more than that of
      enclosed vehicle taxi drivers. With the possible exposure to >=50 ug/m3 PM10, the
      vehicular emission standards should be vigorously enforced. Further investigation
      is warranted to clarify the effect of lung dysfunction on the work and lifestyle
      of motorcycle taxi drivers. IMPLICATIONS: Motorcycle taxi drivers are directly
      exposed to air pollution in their work environment; therefore, their lung
      function might decrease more than that of enclosed vehicle taxi drivers,
      especially when exposed to >=50 ug/m3 PM10. World Health Organization (WHO)
      vehicular emission standards should be recognized and eventually enforced.

PMID- 28745559
TI  - Dyadic Qualitative Analysis of Condom Use Scripts Among Emerging Adult Gay Male
      Couples.
AB  - Sexual risk reduction among gay male couples has received increasing attention in
      light of evidence that primary partners account for many-and possibly most-new
      HIV infections. This study examined the content of condom use scripts in
      interviews conducted with both members of 17 HIV-negative gay male couples. In
      each couple, at least one partner was an emerging adult (aged 18 to 29). Three
      scripts were identified: romantic love, unanticipated condomless anal intercourse
      (CAI), and negotiated safety. Scripts varied in their emphasis on emotional
      factors versus HIV risk reduction, the salience of sexual agreements, and the
      presence of an explicit communication goal. Results indicated that condom use may
      vary for couples as a result of script content and from the fluid adoption of
      scripts across contexts. Results highlighted potential tensions between emotional
      closeness and HIV prevention. Condom use cessation and sexual agreements-a
      potential mechanism for HIV risk reduction-may also serve as expressions of
      intimacy. This implies interventions that facilitate direct communication about
      sexual and relational goals-as well as those that expand couples' repertoires for
      expressing emotional closeness-may enhance sexual health for gay couples,
      particularly during the period of emerging adulthood.

PMID- 28745560
TI  - Genetic perspective of uniparental mitochondrial DNA landscape on the Punjabi
      population, Pakistan.
AB  - To investigate the uniparental genetic structure of the Punjabi population from
      mtDNA aspect and to set up an appropriate mtDNA forensic database, we studied
      maternally unrelated Punjabi (N = 100) subjects from two caste groups (i.e. Arain
      and Gujar) belonging to territory of Punjab. The complete control region was
      elucidated by Sanger sequencing and the subsequent 58 different haplotypes were
      designated into appropriate haplogroups according to the most recently updated
      mtDNA phylogeny. We found a homogenous dispersal of Eurasian haplogroup
      uniformity among the Punjab Province and exhibited a strong connotation with the
      European populations. Punjabi castes are primarily a composite of substantial
      South Asian, East Asian and West Eurasian lineages. Moreover, for the first time
      we have defined the newly sub-haplogroup M52b1 characterized by 16223 T, 16275 G
      and 16438 A in Gujar caste. The vast array of mtDNA variants displayed in this
      study suggested that the haplogroup composition radiates signals of extensive
      genetic conglomeration, population admixture and demographic expansion that was
      equipped with diverse origin, whereas matrilineal gene pool was
      phylogeographically homogenous across the Punjab. This context was further fully
      acquainted with the facts supported by PCA scatterplot that Punjabi population
      clustered with South Asian populations. Finally, the high power of discrimination
      (0.8819) and low random match probability (0.0085%) proposed a worthy
      contribution of mtDNA control region dataset as a forensic database that
      considered a gold standard of today to get deeper insight into the genetic
      ancestry of contemporary matrilineal phylogeny.

PMID- 28745561
TI  - Epidemiology of Hip Flexor and Hip Adductor Strains in National Collegiate
      Athletic Association Athletes, 2009/2010-2014/2015.
AB  - BACKGROUND: Little research has examined the rates and patterns of hip flexor or
      hip adductor strains in student-athletes in the National Collegiate Athletic
      Association (NCAA). PURPOSE: To describe the epidemiology of hip flexor and
      adductor strains in NCAA athletes during the 2009/2010-2014/2015 academic years.
      STUDY DESIGN: Descriptive epidemiology study. METHODS: Rates and patterns of hip
      flexor and adductor strains in collegiate sports were examined in a convenience
      sample of NCAA varsity teams from 25 sports. Rates and distributions of strains
      by mechanism, recurrence, and participation restriction time were examined.
      Injury rate ratios (IRRs) and proportion ratios were calculated to compare rates
      within and between sports by event type, sex, mechanism, recurrence, and
      participation restriction time. RESULTS: A total of 770 hip flexor and 621 hip
      adductor strains were reported, resulting in overall injury rates of 1.60 and
      1.29 per 10,000 athlete-exposures (AEs), respectively. In men, the rate of hip
      flexor strains was 1.81 per 10,000 AEs, and that for hip adductor strains was
      1.71 per 10,000 AEs. In women, the rate of hip flexor strains was 1.59 per 10,000
      AEs, and the rate of hip adductor strains was 1.15 per 10,000 AEs. The highest
      rates of strains were found in men's soccer and men's ice hockey (range, 2.47
      3.77 per 10,000 AEs). Most hip flexor and hip adductor strains occurred in
      practice, but both had higher rates in competition. In sex-comparable sports, hip
      flexor strain rates did not differ between the sexes (IRR = 1.14; 95% CI, 0.96
      1.36), but the rate of hip adductor strains was higher in men than women (IRR =
      1.49; 95% CI, 1.22-1.81). Noncontact was the most common mechanism for both types
      of strains (hip flexor strains, 59.4%; hip adductor strains, 62.5%); 10.1% of hip
      flexor strains and 11.1% of hip adductor strains were recurrent. The highest
      rates of recurrence of both types of strain were found in men's and women's ice
      hockey (range, 16.0%-30.6%). Most hip flexor and hip adductor strains resulted in
      <1 week of participation restriction (hip flexor strains, 83.8%; hip adductor
      strains, 82.9%). CONCLUSION: The NCAA sports with the highest rates of hip flexor
      and hip adductor strains were men's soccer and men's ice hockey. In sex
      comparable sports, men had a higher rate of hip adductor, but not hip flexor,
      strains. Recurrence rates were remarkably high in ice hockey. Male sports teams,
      especially soccer and ice hockey, should place an emphasis on prevention programs
      for hip adductor strains. Secondary prevention programs involving thorough
      rehabilitation and strict return-to-play criteria should be developed and
      implemented to curb the high recurrence rate of these injuries, particularly in
      ice hockey.

PMID- 28745562
TI  - Evaluation of the awareness and effectiveness of IT security programs in a large
      publicly funded health care system.
AB  - BACKGROUND: Electronic health records are becoming increasingly common in the
      health care industry. Although information technology (IT) poses many benefits to
      improving health care and ease of access to information, there are also security
      and privacy risks. Educating health care providers is necessary to ensure proper
      use of health information systems and IT and reduce undesirable outcomes.
      OBJECTIVE: This study evaluated employees' awareness and perceptions of the
      effectiveness of two IT educational training modules within a large publicly
      funded health care system in Canada. METHOD: Semi-structured interviews and focus
      groups included a variety of professional roles within the organisation.
      Participants also completed a brief demographic data sheet. With the consent of
      participants, all interviews and focus groups were audio recorded. Thematic
      analysis and descriptive statistics were used to evaluate the effectiveness of
      the IT security training modules. RESULTS: Five main themes emerged: (i)
      awareness of the IT training modules, (ii) the content of modules, (iii) staff
      perceptions about differences between IT security and privacy issues, (iv) common
      breaches of IT security and privacy, and (v) challenges and barriers to
      completing the training program. Overall, nonclinical staff were more likely to
      be aware of the training modules than were clinical staff. We found e-learning
      was a feasible way to educate a large number of employees. However, health care
      providers required a module on IT security and privacy that was relatable and
      applicable to their specific roles. CONCLUSION: Strategies to improve staff
      education and mitigate against IT security and privacy risks are discussed.
      Future research should focus on integrating health IT competencies into the
      educational programs for health care professionals.

PMID- 28745563
TI  - Validity of routinely collected data in identifying hip fractures at a major
      tertiary hospital in Australia.
AB  - OBJECTIVES: To examine the validity of routinely collected data in identifying
      hip fractures (HFs) and to identify factors associated with incorrect coding.
      METHOD: In a prospective cohort study between January 2014 and June 2016, HFs
      were identified using physician diagnosis and diagnostic imaging and were
      recorded in a Registry. Records of HFs in the health information exchange (HIE)
      were identified using International Statistical Classification of Diseases and
      Related Health Problems, Tenth Revision, Australian Modification/Australian
      Classification of Health Interventions/Australian Coding Standards codes. New HFs
      were estimated by episode of care, hospital admission and with an algorithm. Data
      from the HIE and the Registry were compared. RESULTS: The number of HFs as the
      principal diagnosis (PD) recorded by episode (864) was higher than by admission
      (743), by algorithm (711) and in the Registry (638). The sensitivity was high for
      all methods (90-93%) but the positive predictive value was lower for episode
      (68%) than for admission (80%) or algorithm (81%). The number of HFs with surgery
      recorded in the PD by episode (639), algorithm (630) and in the Registry (623)
      was similar but higher than by admission (589). The episode and algorithm methods
      also had higher sensitivity (91-92%) than the admission method (84%) for HFs with
      surgery. Factors associated with coding errors included subsequent HF, long
      hospital stay, intracapsular fracture, younger age, male, HF without surgery and
      death in hospital. CONCLUSIONS: When it is not practical to use the algorithm for
      regular monitoring of HFs, using PD by admission to estimate total HFs and PD by
      episode in combination with a procedure code to estimate HFs with surgery can
      produce robust estimations.

PMID- 28745564
TI  - Patient and clinician perspectives of an integrated electronic medication
      prescribing and dispensing system: A qualitative study at a multisite Australian
      hospital network.
AB  - BACKGROUND: While clinician attitudes towards electronic prescribing (e
      prescribing) systems have been widely studied, little is known about the
      perspectives of patients, despite being the primary beneficiaries of these
      systems. OBJECTIVE: The objective of this study is to explore and compare patient
      and clinician attitudes towards an integrated e-prescribing and dispensing
      system, in order to guide improvements in system implementation, service delivery
      and enhancements to system functionality. METHOD: A cross-sectional survey was
      developed and administered to patients and multidisciplinary clinicians at a
      multisite Australian metropolitan teaching hospital network in all areas where e
      prescribing was fully implemented. Participants' views on perceived impact and
      valued features of the e-prescribing system were elucidated. RESULTS: Overall,
      783 participants (400 patients and 383 clinicians) completed the survey. Although
      98% of clinicians were aware of the transition to e-prescriptions, only 36% of
      patients were aware prior to the study. Over 80% of patients and clinicians
      perceived improvements in prescribing and dispensing safety and clinician
      workflow; 90% of patients were comfortable with information privacy associated
      with e-prescriptions; and 86% of patients preferred e-prescriptions to
      handwritten prescriptions. Although over 80% of patients valued features that
      improved access to information and medication safety, clinicians were more
      discerning about valued system features. CONCLUSION: The majority of patients and
      clinicians reported a positive impact of e-prescribing on safety and efficiency.
      Both groups valued safe and effective use of medicines, although differences
      existed in the importance placed on key system features. A greater focus on
      patient engagement and communication is needed to optimise the delivery of
      patient-centred care.

PMID- 28745565
TI  - Advances in adult acute lymphoblastic leukemia therapy.
AB  - Progress in adult acute lymphoblastic leukemia (ALL) treatment has been met with
      challenge until recently. A steady improvement in outcomes is being witnessed
      among adults with ALL, and it will be enhanced further with early referral of
      newly diagnosed ALL patients to specialized centers, enrolling more ALL adults in
      clinical trials, adopting pediatric-inspired ALL regimens in younger adults,
      tailoring treatments according to minimal residual disease response and disease
      genetics, incorporating novel therapies and tyrosine kinase inhibitors in
      frontline regimens, early referral to transplant when indicated, expanding the
      donor pool, and developing more effective salvage therapies for
      relapsed/refractory ALL. In this review, we will discuss the most significant
      advances in treating adult ALL observed in the last five years that have the
      potential to enhance adult ALL treatment and outcome.

PMID- 28745566
TI  - Best Practices in Immunohistochemistry in Surgical Pathology and Cytopathology.

PMID- 28745567
TI  - Immunohistochemistry in Gynecologic Pathology: An Example-Based Practical Update.
AB  - CONTEXT: - Immunohistochemical stains are routinely applied in the pathology
      diagnostic workup of gynecologic lesions. The rapidly expanding repertoire of
      available markers helps in refining the diagnostic criteria for each disease
      entity; however, limitations and pitfalls exist. OBJECTIVE: - To provide a
      practical, relevant update on the use of immunohistochemistry for commonly
      encountered differential diagnoses in gynecologic pathology. DATA SOURCES: -
      Literature review and authors' diagnostic experience. CONCLUSIONS: -
      Immunohistochemistry is a helpful adjunct tool in gynecologic pathology. Although
      the primary application is in the diagnostic workup, novel prognostic and
      predictive markers, and immunostains to screen for genetic cancer syndromes, have
      also been recently introduced in the field.

PMID- 28745568
TI  - Application of Immunohistochemistry in Undifferentiated Neoplasms: A Practical
      Approach.
AB  - CONTEXT: - Advances in interventional technology have enhanced the ability to
      safely sample deep-seated suspicious lesions by fine-needle aspiration
      procedures. These procedures often yield scant amounts of diagnostic material,
      yet there is an increasing demand for the performance of more ancillary tests,
      especially immunohistochemistry and, not infrequently, molecular assays, to
      increase diagnostic sensitivity and specificity. A systematic approach to
      conserving diagnostic material is the key, and our previously proposed algorithm
      can be applied aptly in this context. OBJECTIVE: - To elaborate a simple stepwise
      approach to the evaluation of cytology fine-needle aspiration specimens and small
      biopsy tissue specimens, illustrating the algorithmic application of small panels
      of immunohistochemical stains in providing an accurate diagnosis with scant
      amounts of tissue, including the potential pitfalls that may arise while using
      immunohistochemical staining on small quantities of tissue. DATA SOURCES: - The
      sources include literature (PubMed), the first Chinese American Pathologists
      Association Diagnostic Pathology Course material, and the review authors'
      research data as well as practice experience. Seven examples selected from the
      CoPath database at Geisinger Medical Center (Danville, Pennsylvania) are
      illustrated. CONCLUSIONS: - A stepwise approach to the evaluation of fine-needle
      aspiration and small biopsy tissue specimens in conjunction with a small panel of
      select immunohistochemical stains has been successful in accurately assessing the
      lineage/origin of the metastatic tumors of unknown primaries. The awareness of
      the common pitfalls of these biomarkers is essential in many instances.

PMID- 28745569
TI  - Fabry Nephropathy.
AB  - Fabry disease is a rare X-linked recessive lysosomal storage disease. Multiple
      mutations of the GLA gene lead to a deficient or absent activity of the lysosomal
      enzyme alpha-galactosidase A, resulting in progressive glycotriaosylceramide
      accumulation in many organs. Low alpha-galactosidase A activity and mutations in
      the GLA gene confirm the diagnosis. Clinical signs are multisystemic,
      heterogeneous, and progressive. Renal, cardiac, and neurovascular involvements
      are the main life-threatening complications, highlighting the importance of an
      early initiation of enzyme replacement therapy improving long-term outcome. Fabry
      nephropathy lesions are characterized by a cell vacuolization of glomeruli,
      tubules, interstitium, and arteries and by ultrastructural myelin bodies. The
      main histologic differential diagnoses are toxicity of lysosomal inhibitors and
      other renal lipidoses. Renal biopsies are not necessary for diagnosis but have an
      important role in the evaluation of disease evolution and treatment efficiency,
      which is a major challenge for improving outcome and quality of life.

PMID- 28745570
TI  - Soft Tissue Tumor Immunohistochemistry Update: Illustrative Examples of
      Diagnostic Pearls to Avoid Pitfalls.
AB  - CONTEXT: - Current 2013 World Health Organization classification of tumors of
      soft tissue arranges these tumors into 12 groups according to their histogenesis.
      Tumor behavior is classified as benign, intermediate (locally aggressive),
      intermediate (rarely metastasizing), and malignant. In our practice, a general
      approach to reaching a definitive diagnosis of soft tissue tumors is to first
      evaluate clinicoradiologic, histomorphologic, and cytomorphologic features of the
      tumor to generate some pertinent differential diagnoses. These include the
      potential line of histogenesis and whether the tumor is benign or malignant, and
      low or high grade. Although molecular/genetic testing is increasingly finding its
      applications in characterizing soft tissue tumors, currently immunohistochemistry
      still not only plays an indispensable role in defining tumor histogenesis, but
      also serves as a surrogate for underlining molecular/genetic alterations.
      Objective- To provide an overview focusing on the current concepts in the
      classification and diagnosis of soft tissue tumors, incorporating
      immunohistochemistry. This article uses examples to discuss how to use the
      traditional and new immunohistochemical markers for the diagnosis of soft tissue
      tumors. Practical diagnostic pearls, summary tables, and figures are used to show
      how to avoid diagnostic pitfalls. DATA SOURCES: - Data were obtained from
      pertinent peer-reviewed English-language literature and the authors' first-hand
      experience as bone and soft tissue pathologists. CONCLUSIONS: - -The ultimate
      goal for a pathologist is to render a specific diagnosis that provides
      diagnostic, prognostic, and therapeutic information to guide patient care.
      Immunohistochemistry is integral to the diagnosis and management of soft tissue
      tumors.

PMID- 28745571
TI  - The initial level of MLL-partial tandem duplication affects the clinical outcomes
      in patients with acute myeloid leukemia.
AB  - This study aimed to analyze the effects of the initial MLL-partial tandem
      duplication (PTD) expression levels on clinical outcomes in 36 MLL-PTD-positive
      acute myeloid leukemia (AML) patients between 2014 and 2016. ROC curves showed
      1.0% MLL-PTD as the optimal diagnostic cutoff for complete remission (CR).
      Nineteen and 17 cases had MLL-PTD <1.0% (low-level group) and >=1.0% (high-level
      group), respectively. The FAB type distribution (M2 incidence, 100% vs. 53%, p =
      .003) and double-CEBPA-mutation incidence (37% vs. 0%, p = .008) significantly
      differed between the groups, as did the CR rates after the first (78.9% vs.
      35.3%, p = .008) and second chemotherapies (84.2% vs. 47.1%, p = .001). High MLL
      PTD level was the only independent factor affecting the CR rate (odds ratio =
      0.16, p = .024). The 24-month overall survival was significantly lower in the
      high-level group (52.6% vs. 29.4%, p = .043). In conclusion, AML patients with
      high initial MLL-PTD levels have lower induction CR and survival rates.

PMID- 28745572
TI  - Prevalence of Thalassemia Traits and Iron Deficiency Anemia in Sindh, Pakistan.
AB  - Among microcytic hypochromic anemias, the most common disorders are iron
      deficiency anemia and co-pathological conditions such as alpha- or beta
      thalassemia (alpha- or beta-thal) traits. The aim of the present study was to
      determine the frequency and prevalence of iron deficiency anemia and alpha- or
      beta-thal traits based on clinical laboratory data across different ethnic groups
      in five districts of Sindh Province, Pakistan. The present retrospective study
      analyzed 3 years (2012-2015) of encoded and unlinked clinical laboratory data,
      and identified 3030 microcytic hypochromic anemia cases. The data contained
      complete blood counts (CBCs) with smear morphology examinations, serum ferritin
      levels, and hemoglobin (Hb) electrophoreses. After reviewing the data, 994
      confirmed subjects (iron deficiency anemia and alpha- and beta-thal traits) were
      then selected for the present study. The prevalence of alpha- and beta-thal
      traits was highest in Badin district (35.27%), while the prevalence of iron
      deficiency anemia was highest in Larkana district (30.73%). According to the
      ethnic-wise distribution, higher numbers of alpha- and beta-thal trait cases were
      seen in the Sindhi ethnic group [375 (64.21%) and 283 (69.02%), respectively]
      than in the other ethnic groups. In addition, a higher distribution of beta-thal
      trait cases was observed in the Sindhi ethnic group [n = 327 (56%)] in alpha- and
      beta-thal cases overall. Findings from the present study strongly suggested that
      screening is important not only for beta-thal trait but also other traits as
      well. However, careful monitoring of CBC parameters, including red blood cell
      (RBC) indices and morphology, along with clinical findings are essential to
      diagnose carrier cases, especially in high prevalence areas.

PMID- 28745573
TI  - Lives and choices, give and take: Altruism and organ procurement.
AB  - In 2015, Wales introduced a deemed consent: soft opt-out system for organ
      procurement in order to address the chronic shortage of organs for transplant.
      Early statistical evidence suggests that this has had a positive impact on
      cadaveric organ donation. Such a system for procurement has previously been
      dismissed by the Organ Donation Taskforce, who suggested that opting out could
      potentially undermine the concept of donated organs as gifts and this could then
      negatively impact the number of organs offered for transplant. Considerable
      weight was placed upon the need to retain the altruistic gift element associated
      with an opt-in system. This article will consider the role of altruism in an
      organ procurement policy. A broad utilitarian approach will be taken when putting
      forward the arguments in favour of adopting a weak altruism position in a soft
      opt-out system for procurement with a combined registry.

PMID- 28745574
TI  - Age discrimination in healthcare institutions perceived by seniors and students.
AB  - BACKGROUND: Old age-based discrimination is observed as the most tolerated
      prejudice in society and has also been witnessed in healthcare institutions.
      AIMS: The aim of this study is to explore age-based discrimination in healthcare
      institutions as perceived by seniors and students of Medicine and Nursing.
      RESEARCH DESIGN: A multi-method study design, by involving a triangulation
      design. Participants and research context: A purposeful sample of individuals
      aged 65+ (n = 80) and medical and nursing students (n = 100) in the eastern
      region of Poland. Ethical considerations: Ethical approval of the research
      protocol was received from the Ethics Committee at the Medical University of
      Lublin. FINDINGS: 'Old age' was perceived by groups of participants based on
      three themes: (a) positive, (b) negative and (c) neutral connotations. The
      negative connotations predominated. The beginning of old age was defined by the
      metric of age and described by showing the complexity of the ageing process
      involving subjective, objective and societal aspects. Experience of age
      discrimination in healthcare institutions was reported by 24 (30%) seniors and
      witnessed by 47 (47%) students surveyed and for both groups occurred mainly at
      the hospital level and by physicians. Only 48 students (48%) declared a
      willingness to work with the older people in the future, and barriers were
      reported at the personal and professional levels, and also in some visions of
      older people. CONCLUSION: The conceptualization of old age as reported by seniors
      and students mainly carried negative connotations, reflecting the profoundly
      based stereotypes within society regarding the older people. Seniors have
      reported being exposed to ageism and have witnessed ageism episodes in HCIs;
      also, students have faced ageism episodes during their clinical education. There
      is a need for ethical education within medical and nursing courses to shape
      positive attitudes towards the older people. A positive vision of ageing should
      be promoted not only among young people but also among adults and older people to
      avoid self-stereotyping of older people and seeing old age from negative
      perspective.

PMID- 28745575
TI  - Use of exome sequencing to determine the full profile of genetic variants in the
      fluoropyrimidine pathway in colorectal cancer patients affected by severe
      toxicity.
AB  - AIM: To identify genetic variants associated with capecitabine toxicity in
      fluoropyrimidine pathway genes using exome sequencing. PATIENTS & METHODS: Exomes
      from eight capecitabine-treated patients with severe adverse reactions (grade
      >2), among a population of 319, were sequenced (Ion Proton). SNPs in genes
      classified as potentially damaging (Sorting Intolerant from Tolerant and
      Polymorphism Phenotyping v2) were tested for association with toxicity in a
      validation cohort of 319 capecitabine-treated patients. RESULTS: A total of 17
      nonsynonymous genetic variants were identified. Of these, five putative damaging
      SNPs in DPYD, ABCC4 and MTHFR were genotyped in the validation cohort. DPYD
      rs1801160 was associated with the risk of toxicity (p = 0.029) and MTHFR
      rs1801133 with delayed administration of chemotherapy due to toxicity (p =
      0.047). CONCLUSION: Exome sequencing revealed two specific biomarkers of the risk
      of toxicity to capecitabine.

PMID- 28745576
TI  - Association of CYP2C19*2 polymorphism with clopidogrel response and 1-year major
      adverse cardiovascular events in a multiethnic population with drug-eluting
      stents.
AB  - BACKGROUND: Patients undergoing elective percutaneous coronary intervention (PCI)
      with drug-eluting stents (DES) who have impaired clopidogrel response, have a
      higher risk of subsequent major adverse cardiovascular events (MACE). AIM OF THE
      STUDY: To establish the relationship between CYP2C19 genotype, clopidogrel
      responsiveness and 1-year MACE. MATERIALS & METHODS: Aspirin/clopidogrel
      responses were assessed with Multiplate Analyzer and CYP2C19*2 allele by
      SpartanRx. RESULTS: A total of 42.0% carried >=1 CYP2C19*2 allele. Prevalences of
      aspirin and clopidogrel high on-treatment platelet reactivity (HPR; local
      cutoffs: 300 AU*min for aspirin and 600 AU*min for clopidogrel) were 11.5% and
      19.8% respectively. In multivariate ana-lysis, clopidogrel HPR was found to be an
      independent predictor for 1-year MACE (adj HR: 3.48, p = 0.022 ). CONCLUSION:
      Having clopidogrel HPR could be a potentially modifiable risk factor guided by
      phenotyping.

PMID- 28745577
TI  - Advanced cancer pain: the search for genetic factors correlated with
      interindividual variability in opioid requirement.
AB  - AIM: To assess association between genetic variants and opioid requirement in
      cancer patients. MATERIALS & METHODS: A prospective observational trial of 243
      advanced cancer patients with inadequate analgesia treated by the palliative care
      team was analyzed for ABCB1, ARRB2, COMT, GCH1, IL1RN, KCNJ6, OPRM1, RHBDF2,
      SCN9A and Stat6 polymorphisms. RESULTS: For patients carrying OPRM1 118AG/GG and
      COMT 472GG (Val158Val) or these genotypes alone, a significant higher median
      percentage dose increase was observed (95.2% [32.8-345]) compared with OPRM1
      118AA and COMT 472GA/AA (158Met allele carriers; 48.5% [0-98.8]; p = 0.0016). No
      associations were found with morphine equivalent dose after consultation
      palliative care team or ketamine use. CONCLUSION: Patients with the combined
      OPRM1 118AG/GG and COMT 472GG genotype required 50% higher dose increase for
      sufficient analgesia.

PMID- 28745578
TI  - Cost-effectiveness of G5 Mobile continuous glucose monitoring device compared to
      self-monitoring of blood glucose alone for people with type 1 diabetes from the
      Canadian societal perspective.
AB  - AIMS: To evaluate the cost-effectiveness of real-time continuous glucose
      monitoring (CGM) compared to self-monitoring of blood glucose (SMBG) alone in
      people with type 1 diabetes (T1DM) using multiple daily injections (MDI) from the
      Canadian societal perspective. METHODS: The IMS CORE Diabetes Model (v.9.0) was
      used to assess the long-term (50 years) cost-effectiveness of real-time CGM (G5
      Mobile CGM System; Dexcom, Inc., San Diego, CA) compared with SMBG alone for a
      cohort of adults with poorly-controlled T1DM. Treatment effects and baseline
      characteristics of patients were derived from the DIAMOND randomized controlled
      clinical trial; all other assumptions and costs were sourced from published
      research. The accuracy and clinical effectiveness of G5 Mobile CGM is the same as
      the G4 Platinum CGM used in the DIAMOND randomized clinical trial. Base case
      assumptions included (a) baseline HbA1c of 8.6%, (b) change in HbA1c of -1.0% for
      CGM users vs -0.4% for SMBG users, and (c) disutilities of -0.0142 for non-severe
      hypoglycemic events (NSHEs) and severe hypoglycemic events (SHEs) not requiring
      medical intervention, and -0.047 for SHEs requiring medical resources. Treatment
      costs and outcomes were discounted at 1.5% per year. RESULTS: The incremental
      cost-effectiveness ratio for the base case G5 Mobile CGM vs SMBG was $33,789
      CAD/quality-adjusted life-year (QALY). Sensitivity analyses showed that base case
      results were most sensitive to changes in percentage reduction in hypoglycemic
      events and disutilities associated with hypoglycemic events. The base case
      results were minimally impacted by changes in baseline HbA1c level, incorporation
      of indirect costs, changes in the discount rate, and baseline utility of
      patients. CONCLUSIONS: The results of this analysis demonstrate that G5 Mobile
      CGM is cost-effective within the population of adults with T1DM using MDI,
      assuming a Canadian willingness-to-pay threshold of $50,000 CAD per QALY.

PMID- 28745579
TI  - Re: A dynamic approach for outpatient scheduling.

PMID- 28745580
TI  - Pharmacogenomic considerations in the treatment of muscle-invasive bladder
      cancer.
AB  - Recent advances in next-generation sequencing techniques have greatly improved
      our understanding of the genomic alterations in bladder cancer. Cisplatin-based
      chemotherapy provides a viable treatment option in the neoadjuvant, adjuvant and
      metastatic setting in a selected group of patients, but chemoresistance is a
      major problem. The underlying mechanisms of treatment resistance are poorly
      understood and elucidating these pathways will subsequently lead to improved
      patient selection, less unnecessary drug-related toxicity, improved patient
      outcome and decreased healthcare costs. This review provides an overview of
      mechanisms of chemoresistance and describes the current knowledge on how the
      genomic landscape influences therapy outcome in muscle-invasive bladder cancer
      patients.

PMID- 28745581
TI  - Clinical correlates and prognostic value of different metastatic sites in
      patients with malignant melanoma of the skin: a SEER database analysis.
AB  - BACKGROUND: Population-based data on the clinical correlates and prognostic value
      of the pattern of metastases among patients with cutaneous melanoma are needed.
      METHODS: Surveillance, Epidemiology and End Results (SEER) database (2010-2013)
      has been explored through SEER*Stat program. For each of six distant metastatic
      sites (bone, brain, liver, lung, distant lymph nodes, and skin/subcutaneous),
      relevant correlation with baseline characteristics were reported. Survival
      analysis has been conducted through Kaplan-Meier analysis, and multivariate
      analysis has been conducted through a Cox proportional hazard model. RESULTS: A
      total of 2691 patients with metastatic cutaneous melanoma were identified in the
      period from 2010 to 2013. Patients with isolated skin/subcutaneous metastases
      have the best overall and melanoma-specific survival (MSS) followed by patients
      with isolated distant lymph node metastases followed by patients with isolated
      lung metastases. Patients with isolated liver, bone, or brain metastases have the
      worst overall and MSS (p < .0001 for both end points). Multivariate analysis
      revealed that age more than 70 at diagnosis (p = .012); multiple sites of
      metastases (p <.0001), no surgery to the primary tumor (p <.0001), and no surgery
      to the metastatic disease (p < .0001) were associated with worse overall survival
      (OS). For MSS, nodal positivity (p = .038), multiple sites of metastases (p <
      .0001), no surgery to the primary tumor (p < .0001), and no surgery to the
      metastatic disease (p < .0001) were associated with worse survival. CONCLUSIONS:
      The prognosis of metastatic cutaneous melanoma patients differs considerably
      according to the site of distant metastases. Further prospective studies are
      required to evaluate the role of local treatment in the management of metastatic
      disease.

PMID- 28745582
TI  - CYP2C19-guided antiplatelet therapy: a cost-effectiveness analysis of 30-day and
      1-year outcomes following percutaneous coronary intervention.
AB  - AIM: Determine whether using CYP2C19 genotype to optimize antiplatelet therapy
      selection is cost effective over the initial 30 days and 1-year following
      percutaneous coronary intervention. MATERIALS & METHODS: A cost-effectiveness
      analysis compared 30-day and 1-year outcomes and cost across three treatment
      strategies (universal clopidogrel, universal prasugrel, genotype-guided) in a
      hypothetical cohort. RESULTS: Base-case scenario results at 30 days indicated
      that the incremental cost per major cardiovascular or bleeding event avoided for
      genotype-guided treatment was US$8525 and US$42,198 compared with universal
      clopidogrel and prasugrel, respectively. Probabilistic sensitivity analysis
      demonstrated that genotype-guided treatment was cost effective over 30 days and 1
      year in 62 and 70% of simulations, respectively. CONCLUSION: Implementing a
      CYP2C19 genotype-guided approach to antiplatelet therapy could have a positive
      economic impact by preventing readmissions following percutaneous coronary
      intervention.

PMID- 28745583
TI  - Early health technology assessments in pharmacogenomics: a case example in
      cardiovascular drugs.
AB  - AIM: To assess the required characteristics (cost, sensitivity and specificity)
      of a pharmacogenomic test for being a cost-effective prevention of angiotensin
      converting enzyme inhibitors induced angioedema. Furthermore, we assessed the
      influence of only testing high-risk populations. MATERIALS & METHODS: A decision
      tree was used. RESULTS: With a willingness-to-pay threshold of ?20,000 and
      ?80,000 per quality adjusted life year, a 100% sensitive and specific test may
      have a maximum cost of ?1.30 and ?1.95, respectively. When only genotyping high
      risk populations, the maximum test price would be ?5.03 and ?7.55, respectively.
      CONCLUSION: This theoretical pharmacogenomic test is only cost-effective at high
      specificity, high sensitivity and a low price. Only testing high-risk populations
      yields more realistic maximum test prices for cost-effectiveness of the
      intervention.

PMID- 28745584
TI  - The heritability of multi-modal connectivity in human brain activity.
AB  - Patterns of intrinsic human brain activity exhibit a profile of functional
      connectivity that is associated with behaviour and cognitive performance, and
      deteriorates with disease. This paper investigates the relative importance of
      genetic factors and the common environment between twins in determining this
      functional connectivity profile. Using functional magnetic resonance imaging
      (fMRI) on 820 subjects from the Human Connectome Project, and
      magnetoencephalographic (MEG) recordings from a subset, the heritability of
      connectivity among 39 cortical regions was estimated. On average over all
      connections, genes account for about 15% of the observed variance in fMRI
      connectivity (and about 10% in alpha-band and 20% in beta-band oscillatory power
      synchronisation), which substantially exceeds the contribution from the
      environment shared between twins. Therefore, insofar as twins share a common
      upbringing, it appears that genes, rather than the developmental environment,
      have the dominant role in determining the coupling of neuronal activity.

PMID- 28745585
TI  - Maturation of selected human mitochondrial tRNAs requires deadenylation.
AB  - Human mitochondria contain a genome (mtDNA) that encodes essential subunits of
      the oxidative phosphorylation system. Expression of mtDNA entails multi-step
      maturation of precursor RNA. In other systems, the RNA life cycle involves
      surveillance mechanisms, however, the details of RNA quality control have not
      been extensively characterised in human mitochondria. Using a mitochondrial
      ribosome profiling and mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq)
      assay, we identify the poly(A)-specific exoribonuclease PDE12 as a major factor
      for the quality control of mitochondrial non-coding RNAs. The lack of PDE12
      results in a spurious polyadenylation of the 3' ends of the mitochondrial (mt-)
      rRNA and mt-tRNA. While the aberrant adenylation of 16S mt-rRNA did not affect
      the integrity of the mitoribosome, spurious poly(A) additions to mt-tRNA led to
      reduced levels of aminoacylated pool of certain mt-tRNAs and mitoribosome
      stalling at the corresponding codons. Therefore, our data uncover a new,
      deadenylation-dependent mtRNA maturation pathway in human mitochondria.

PMID- 28745587
TI  - The global HIV/AIDS epidemic-progress and challenges.

PMID- 28745586
TI  - Unexpected sequences and structures of mtDNA required for efficient transcription
      from the first heavy-strand promoter.
AB  - Human mtDNA contains three promoters, suggesting a need for differential
      expression of the mitochondrial genome. Studies of mitochondrial transcription
      have used a reductionist approach, perhaps masking differential regulation. Here
      we evaluate transcription from light-strand (LSP) and heavy-strand (HSP1)
      promoters using templates that mimic their natural context. These studies reveal
      sequences upstream, hypervariable in the human population (HVR3), and downstream
      of the HSP1 transcription start site required for maximal yield. The carboxy
      terminal tail of TFAM is essential for activation of HSP1 but not LSP. Images of
      the template obtained by atomic force microscopy show that TFAM creates loops in
      a discrete region, the formation of which correlates with activation of HSP1;
      looping is lost in tail-deleted TFAM. Identification of HVR3 as a transcriptional
      regulatory element may contribute to between-individual variability in
      mitochondrial gene expression. The unique requirement of HSP1 for the TFAM tail
      may enable its regulation by post-translational modifications.

PMID- 28745589
TI  - Medical education reform in China.

PMID- 28745588
TI  - Growing concerns of hepatitis E in Europe.

PMID- 28745590
TI  - Saving lives with equity-the efficient route to the SDGs.

PMID- 28745591
TI  - 90-90-90 and ending AIDS: necessary and feasible.

PMID- 28745592
TI  - The International AIDS Society-Lancet Commission on the future of the HIV
      response and global health.

PMID- 28745593
TI  - Offline: NCDs-why are we failing?

PMID- 28745594
TI  - The HIV response in Ukraine: at a crossroads.

PMID- 28745595
TI  - Public health commissioner appointed to lead US CDC.

PMID- 28745596
TI  - Putting LGBTQ people back on the canvas of history.

PMID- 28745597
TI  - Ending AIDS: myth or reality?

PMID- 28745598
TI  - Nelly Mugo and the response to HIV: more than just PrEP advocacy.

PMID- 28745599
TI  - The sun is shining on Cyprus's National Health Service.

PMID- 28745600
TI  - NHS manifesto: the missing piece of the puzzle.

PMID- 28745601
TI  - NHS manifesto: the missing piece of the puzzle - Authors' reply.

PMID- 28745602
TI  - Diagnostic accuracy of the PROMIS study.

PMID- 28745603
TI  - Diagnostic accuracy of the PROMIS study - Authors' reply.

PMID- 28745604
TI  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. A new drug
      class for the treatment of hypercholesterolemia.

PMID- 28745605
TI  - Sex and age affect agreement between fasting plasma glucose and glycosylated
      hemoglobin for diagnosis of dysglycemia.
AB  - AIM: To assess agreement between fasting plasma glucose (FPG) and hemoglobin A1c
      (HbA1c) levels for diagnosis of dysglycemia (diabetes and risk of diabetes),
      overall and depending on clinical characteristics. METHODS: The study enrolled
      1020 adult subjects without drug-treated diabetes who underwent a laboratory test
      at a Spanish health care center. The criteria for dysglycemia of the American
      Diabetes Association were used. A logistic regression analysis was used to
      predict de novo diagnosis of dysglycemia based on sex, age, body mass index,
      anemia, and iron levels. RESULTS: Overall prevalence of dysglycemia was 28.04%,
      and was identified by FPG only in 13.63% of subjects, by both FPG and HbA1c in
      7.65%, and by HbA1c only in 6.76% (de novo diagnoses). Independent predictors of
      de novo diagnoses based on HbA1c were female sex (odds ratio [OR]: 2.119, 95%
      confidence interval [CI]: 1.133-4.020; p<0.020), age (OR for 42-56 years: 2.541,
      95% CI: 0.634-17.140; OR for >=57 years: 5.656, 95% CI: 1.516-36.980; overall
      p<0.007), and serum ferritin levels (borderline significance). CONCLUSIONS: In
      this study population, agreement between FPG and HbA1c for diagnosis of
      dysglycemia was poor, with FPG being the test that identified more subjects. De
      novo diagnoses based on HbA1c were more common in females and increased with age.

PMID- 28745606
TI  - Ghrelin levels could be involved in the improvement of insulin resistance after
      bariatric surgery.
AB  - BACKGROUND AND OBJECTIVE: Ghrelin is a gastrointestinal peptide involved in
      regulation of body weight and energy balance. However, its behavior after
      bariatric surgery and its relationship to insulin resistance are still
      controversial. A simultaneous assessment was made of the association between
      changes in ghrelin levels and different variables after three types of bariatric
      surgery. PATIENTS AND METHODS: Ghrelin levels were measured in 103 morbidly obese
      subjects before and 6 months after bariatric surgery (Roux-en-Y gastric bypass
      (RYGB), biliopancreatic diversion of Scopinaro (BPD), and sleeve gastrectomy
      (SG)), and in 21 non-obese subjects. RESULTS: Ghrelin levels increased after RYGB
      (p<0.05), were unchanged after BPD, and decreased after SG (p<0.05). The percent
      change in ghrelin levels (Delta-ghrelin) was associated to the type of surgery in
      a multiple linear regression model (p=0.017). When the same analysis was only
      performed in subjects in whom the gastric fundus was maintained (RYGB and BPD),
      Delta-ghrelin was negatively associated to Delta-HOMA-IR (p=0.001). In morbidly
      obese subjects who underwent RYGB and BPD, the odds ratio of a lower Delta-HOMA
      IR in patients with Delta-ghrelin in the Q1 quartile versus those with Delta
      ghrelin in the Q4 quartile was 8.74 (1.73-44.06) (p=0.009). CONCLUSIONS: Changes
      in ghrelin levels after bariatric surgery are associated to the presence or
      absence of the gastric fundus. After bariatric surgery, the decrease in insulin
      resistance was associated to increased ghrelin levels in procedures in which the
      fundus is not excluded.

PMID- 28745607
TI  - Glucose metabolism before and after treatment in patients with acromegaly.
AB  - INTRODUCTION: The aim of this study was to ascertain the prevalence of
      carbohydrate changes in patients diagnosed with acromegaly, and to evaluate what
      happens two years after treatment. It was also intended to assess which factors
      are associated to the occurrence of such changes. MATERIAL AND METHODS: Sixty-six
      patients diagnosed with acromegaly at our center were enrolled and divided into
      groups with normal glucose metabolism, prediabetes, and diabetes. After 2 years
      of treatment of acromegaly, prevalence carbohydrate changes was assessed again
      depending on the patient condition (cured, controlled with medical treatment, or
      uncontrolled). RESULTS: At the time of diagnosis of acromegaly, 27.3% of the
      patients had diabetes (n=18), 39.4% had prediabetes (n=26), and 33.3% had no
      changes (n=22). Significant differences were found in IGF-1 and z-score of IGF-1
      (median of 18.1 in diabetics and 10.6 in non-diabetics, P=.005). Two years after
      treatment, there was a significant decrease in the prevalence of diabetes and
      prediabetes in cured patients (from 29.2% to 8.3% and from 45.8% to 16.7%,
      respectively, P=.003), but not in patients controlled with medical treatment or
      not controlled. CONCLUSION: At our center, 66.6% of patients with acromegaly had
      changes in carbohydrate metabolism at diagnosis, with a prevalence of diabetes of
      27.3%. Two years after treatment of acromegaly, prevalence of diabetes and
      prediabetes decreased in cured patients.

PMID- 28745608
TI  - Metabolic syndrome in Mexican children: Low effectiveness of diagnostic
      definitions.
AB  - BACKGROUND: Early identification of children with metabolic syndrome (MS) is
      essential to decrease the risk of developing diabetes and cardiovascular disease
      in adulthood. Detection of MS is however challenging because of the different
      definitions for diagnosis; as a result, preventive actions are not taken in some
      children at risk. The study objective was therefore to compare prevalence of MS
      in children according to the IDF, NCEP-ATP-III, Cook, de Ferranti and Weiss
      definitions, considering insulin resistance (IR) markers such as HOMA-IR and/or
      metabolic index (MI). METHODS: A total of 508 Mexican children (aged 9 to 13
      years) from seven schools were enrolled in a cross-sectional study. Somatometric,
      biochemical, and hormonal measurements were evaluated. RESULTS: Frequency of MS
      was 2.4-45.9% depending on the definition used. Frequency of IR in children not
      diagnosed with MS was 12.4-25.2% using HOMA-IR and 4.0-16.3% using MI. When HOMA
      IR or MI was included in each of the definitions, frequency of MS was 8.5-50.2%
      and 7.7-46.9% respectively. The kappa value including HOMA-IR and/or MI was
      greater than 0.8. CONCLUSIONS: This study demonstrated the poor effectiveness of
      the current criteria used to diagnose MS in Mexican children, as shown by the
      variability in the definitions and by the presence of IR in children who not
      diagnosed with MS. Inclusion of HOMA-IR and/or MI in definitions of MS (thus
      increasing agreement between them) decreases the chance of excluding children at
      risk and allows for MS prevalence between populations.

PMID- 28745609
TI  - Budget impact of continuous subcutaneous insulin infusion therapy in patients
      with type 1 diabetes who experience severe recurrent hypoglycemic episodes in
      Spain.
AB  - OBJECTIVE: Hypoglycemia is one of the most common complications to achieve a good
      metabolic control, and has been listed by several scientific associations as a
      common indication to start treatment with continuous subcutaneous insulin
      infusion (CSII). Use of CSII is still residual in Spain as compared to
      neighbouring countries, and cost of acquisition cost is one of the main reasons.
      This study estimates the budget impact of treatment with CSII, as compared to
      multiple daily insulin injections, of patients with type 1 diabetes mellitus who
      experience recurrent severe hypoglycemia episodes from the National Healthcare
      System perspective. METHODS: Budget impact was based on a retrospective,
      observational study evaluating the efficacy of CSII in patients with type 1
      diabetes mellitus conducted at Hospital Clinic i Universitari in Barcelona, where
      one of the main indications for switching to CSII were recurrent severe
      hypoglycemia episodes. The mean number of annual episodes was 1.33 in the two
      years prior to CSII start and 0.08 in the last two years of follow up (p=0.003).
      Costs of treatment and major hypoglycemic events over a four-year period were
      considered. Costs were taken from different Spanish data sources and expressed in
      ? of 2016. RESULTS: Treatment with CSII increased costs by ?9,509 per patient as
      compared to multiple daily insulin injections (?11,902-?2,393). Cost associated
      to severe hypoglycemic events decreased by ?19,330 per patient treated with CSIII
      (?1,371-?20,701). Results suggest mean total savings of ?9,821 per patient during
      the four-year study period. CONCLUSION: The higher costs associated to CSII
      therapy may be totally offset by the severe hypoglycemic events prevented.

PMID- 28745610
TI  - Clinically non-functioning pituitary adenomas: Pathogenic, diagnostic and
      therapeutic aspects.
AB  - Clinically non-functioning pituitary adenomas (NFPAs) are among the most common
      tumors in the sellar region. These lesions do not cause a hormonal hypersecretion
      syndrome, and are therefore found incidentally (particularly microadenomas) or
      diagnosed based on compressive symptoms such as headache and visual field
      defects, as well as clinical signs of pituitary hormone deficiencies.
      Immunohistochemically, more than 45% of these adenomas stain for gonadotropins or
      their subunits and are therefore called gonadotropinomas, while 30% of them show
      no immunostaining for any hormone and are known as null cell adenomas. The
      diagnostic approach to NFPAs should include visual field examination, an
      assessment of the integrity of all anterior pituitary hormone systems, and
      magnetic resonance imaging of the sellar region to define tumor size and
      extension. The treatment of choice is transsphenoidal resection of the adenoma,
      which in many instances cannot be completely accomplished. The recurrence rate
      after surgery may be up to 30%. Persistent or recurrent adenomas are usually
      treated with radiation therapy. In a small proportion of these cases, drug
      treatment with dopamine agonists and, to a lesser extent, somatostatin analogs
      may achieve reduction or at least stabilization of the tumor.

PMID- 28745611
TI  - Limitations of current thyroid function tests.

PMID- 28745612
TI  - PEMETREXED-INDUCED PSEUDOCELLULITIS - A RARE CUTANEOUS ADVERSE REACTION TO MULTI
      TARGETED ANTIFOLATE THERAPY.
AB  - Pemetrexed is a multi-targeted folate antagonists approved for non-small cell
      lung cancer and other malignancies. Adverse cutaneous reactions have been
      reported in up to 1/3 of patients treated. A rare cutaneous adverse reaction is
      pseudocellulitis. We report about a 62-year-old male patient treated with a
      combination of cisplatin and pemetrexed for non-small cell lung cancer stage IV
      who developed about 4 months after initiation of treatment painful, non-febrile
      erythematous lesions on feet and lower legs. There was no lymphadenopathy and no
      general malaise. Laboratory investigations detected increased level of C-reactive
      protein but normal values of procalcitonin. A skin biopsy revealed a mild
      interface dermatitis. Antifolate treatment was stopped and he received oral and
      topical corticosteroids, compression therapy and supplementation with folate and
      vitamin B. A complete remission of skin eruptions was achieved. Pemetrexed
      induced pseudocellulitis is a possible, but rare complication of treatment that
      oncologists and dermatologists should know. Systemic antibiosis is unnecessary.

PMID- 28745613
TI  - Scalable transfer of vertical graphene nanosheets for flexible supercapacitor
      applications.
AB  - Vertical graphene nanosheets (VGN) are the material of choice for application in
      next-generation electronic devices. The growing demand for VGN-based flexible
      devices for the electronics industry brings in restriction on VGN growth
      temperature. The difficulty associated with the direct growth of VGN on flexible
      substrates can be overcome by adopting an effective strategy of transferring the
      well-grown VGN onto arbitrary flexible substrates through a soft chemistry route.
      In the present study, we report an inexpensive and scalable technique for the
      polymer-free transfer of VGN onto arbitrary substrates without disrupting its
      morphology, structure, and properties. After transfer, the morphology, chemical
      structure, and electrical properties are analyzed by scanning electron
      microscopy, Raman spectroscopy, x-ray photoelectron spectroscopy, and four-probe
      resistive methods, respectively. The wetting properties are studied from the
      water contact angle measurements. The observed results indicate the retention of
      morphology, surface chemistry, structure, and electronic properties. Furthermore,
      the storage capacity of the transferred VGN-based binder-free and current
      collector-free flexible symmetric supercapacitor device is studied. A very low
      sheet resistance of 670 Omega/? and excellent supercapacitance of 158 MUF cm-2
      with 86% retention after 10 000 cycles show the prospect of the damage-free VGN
      transfer approach for the fabrication of flexible nanoelectronic devices.

PMID- 28745614
TI  - Engineering magnetism at functional oxides interfaces: manganites and beyond.
AB  - The family of transition metal oxides (TMOs) is a large class of magnetic
      materials that has been intensively studied due to the rich physics involved as
      well as the promising potential applications in next generation electronic
      devices. In TMOs, the spin, charge, orbital and lattice are strongly coupled, and
      significant advances have been achieved to engineer the magnetism by different
      routes that manipulate these degrees of freedom. The family of manganites is a
      model system of strongly correlated magnetic TMOs. In this review, using
      manganites thin films and the heterostructures in conjunction with other TMOs as
      model systems, we review the recent progress of engineering magnetism in TMOs. We
      first discuss the role of the lattice that includes the epitaxial strain and the
      interface structural coupling. Then we look into the role of charge, focusing on
      the interface charge modulation. Having demonstrated the static effects, we
      continue to review the research on dynamical control of magnetism by electric
      field. Next, we review recent advances in heterostructures comprised of high T c
      cuprate superconductors and manganites. Following that, we discuss the emergent
      magnetic phenomena at interfaces between 3d TMOs and 5d TMOs with strong spin
      orbit coupling. Finally, we provide our outlook for prospective future
      directions.

PMID- 28745615
TI  - Topological phases in double layers of bismuthene and antimonene.
AB  - Two-dimensional topological insulators show great promise for spintronic
      applications. Much attention has been placed on single atomic or molecular
      layers, such as bismuthene. The selections of such materials are, however,
      limited. To broaden the base of candidate materials with desirable properties for
      applications, we report herein an exploration of the physics of double layers of
      bismuthene and antimonene. The electronic structure of a film depends on the
      number of layers, and it can be modified by epitaxial strain, by changing the
      effective spin-orbit coupling strength, and by the manner in which the layers are
      geometrically stacked. First-principles calculations for the double layers reveal
      a number of phases, including topological insulators, topological semimetals,
      Dirac semimetals, trivial semimetals, and trivial insulators. Their phase
      boundaries and the stability of the phases are investigated. The results
      illustrate a rich pattern of phases that can be realized by tuning lattice strain
      and effective spin-orbit coupling.

PMID- 28745616
TI  - Non-classical behaviour of higher valence dopants in chromium (III) oxide by a Cr
      vacancy compensation mechanism.
AB  - Modification of metal oxides with dopants that have a stable oxidation in their
      parent oxides which is higher than the host system is expected to introduce extra
      electrons into the material to improve carrier mobility. This is essential for
      applications in catalysis, SOFCs and solar energy materials. Density functional
      theory calculations are used to investigate the change in electronic and
      geometric structure of chromium (III) oxide by higher valence dopants, namely;
      Ce, Ti, V and Zr. For single metal doping, we find that the dopants with variable
      oxidation states, Ce, Ti and V, adopt a valence state of  +3, while Zr dopant has
      a  +4 oxidation state and reduces a neighbouring Cr cation. Chromium vacancy
      formation is greatly enhanced for all dopants, and favoured over oxygen vacancy
      formation. The Cr vacancies generate holes which oxidise Ce, Ti and V from  +3 to
      +4, while also oxidising lattice oxygen sites. For Zr doping, the generated
      holes oxidise the reduced Cr2+ cation back to Cr3+ and also two lattice oxygen
      atoms. Three metal atoms in the bulk lattice facilitate spontaneous Cr vacancy
      from charge compensation. A non-classical compensation mechanism is observed for
      Ce, Ti and V; all three metals are oxidised from  +3 to  +4, which explains
      experimental observations that these metals have a  +4 oxidation state in Cr2O3.
      Charge compensation of the three Zr metals proceeds by a classical higher valence
      doping mechanism; the three dopants reduce three Cr cations, which are
      subsequently charge compensated by a Cr vacancy oxidising three Cr2+ to Cr3+. The
      compensated structures are the correct ground state electronic structure for
      these doped systems, and used as a platform to investigate cation/anion vacancy
      formation. Unlike the single metal doped bulks, preference is now given for
      oxygen vacancy formation over Cr vacancy formation, indicating that the dopants
      increase the reducibility of Cr2O3 with Ce doping showing the strongest
      enhancement. The importance of the correct ground state in determining the
      formation of defects is emphasised.

PMID- 28745617
TI  - Influence of swift heavy ion irradiation on the photoluminescence of Si
      nanoparticles and defects in SiO2.
AB  - The influence of swift heavy ion (SHI) irradiation on the photoluminescence (PL)
      of silicon nanoparticles (SiNPs) and defects in SiO2-film is investigated. SiNPs
      were formed by implantation of 70 keV Si+ and subsequent thermal annealing to
      produce optically active SiNPs and to remove implantation-induced defects. Seven
      different ion species with energy between 3-36 MeV and fluence from 1011-1014 cm
      2 were employed for irradiation of the implanted samples prior to the thermal
      annealing. Induced changes in defect and SiNP PL were characterized and
      correlated with the specific energy loss of the employed SHIs. We find that SHI
      irradiation, performed before the thermal annealing process, affects both defect
      and SiNP PL. The change of defect and SiNP PL due to SHI irradiation is found to
      show a threshold-like behaviour with respect to the electronic stopping power,
      where a decrease in defect PL and an anticorrelated increase in SiNP PL after the
      subsequent thermal annealing are observed for electronic stopping exceeding 3-5
      keV nm-1. PL intensities are also compared as a function of total energy
      deposition and nuclear energy loss. The observed effects can be explained by ion
      track formation as well as a different type of annealing mechanisms active for
      SHI irradiation compared to the thermal annealing.

PMID- 28745618
TI  - Few-layer MoS2 as nitrogen protective barrier.
AB  - We report experimental and theoretical investigations of the observed barrier
      behavior of few-layer MoS2 against nitrogenation. Owing to its low-strength
      shearing, low friction coefficient, and high lubricity, MoS2 exhibits the
      demeanor of a natural N-resistant coating material. Raman spectroscopy is done to
      determine the coating capability of MoS2 on graphene. Surface morphology of our
      MoS2/graphene heterostructure is characterized by using optical microscopy,
      scanning electron microscopy, and atomic force microscopy. In addition, density
      functional theory-based calculations are performed to understand the energy
      barrier performance of MoS2 against nitrogenation. The penetration of nitrogen
      atoms through a defect-free MoS2 layer is prevented by a very high vertical
      diffusion barrier, indicating that MoS2 can serve as a protective layer for the
      nitrogenation of graphene. Our experimental and theoretical results show that
      MoS2 material can be used both as an efficient nanocoating material and as a
      nanoscale mask for selective nitrogenation of graphene layer.

PMID- 28745619
TI  - Quantification of Drosophila Grooming Behavior.
AB  - Drosophila grooming behavior is a complex multi-step locomotor program that
      requires coordinated movement of both forelegs and hindlegs. Here we present a
      grooming assay protocol and novel chamber design that is cost-efficient and
      scalable for either small or large-scale studies of Drosophila grooming. Flies
      are dusted all over their body with Brilliant Yellow dye and given time to remove
      the dye from their bodies within the chamber. Flies are then deposited in a set
      volume of ethanol to solubilize the dye. The relative spectral absorbance of dye
      ethanol samples for groomed versus ungroomed animals are measured and recorded.
      The protocol yields quantitative data of dye accumulation for individual flies,
      which can be easily averaged and compared across samples. This allows
      experimental designs to easily evaluate grooming ability for mutant animal
      studies or circuit manipulations. This efficient procedure is both versatile and
      scalable. We show work-flow of the protocol and comparative data between WT
      animals and mutant animals for the Drosophila type I Dopamine Receptor (DopR).

PMID- 28745620
TI  - Identification Of Erythromyeloid Progenitors And Their Progeny In The Mouse
      Embryo By Flow Cytometry.
AB  - Macrophages are professional phagocytes from the innate arm of the immune system.
      In steady-state, sessile macrophages are found in adult tissues where they act as
      front line sentinels of infection and tissue damage. While other immune cells are
      continuously renewed from hematopoietic stem and progenitor cells (HSPC) located
      in the bone marrow, a lineage of macrophages, known as resident macrophages, have
      been shown to be self-maintained in tissues without input from bone marrow HSPCs.
      This lineage is exemplified by microglia in the brain, Kupffer cells in the liver
      and Langerhans cells in the epidermis among others. The intestinal and colon
      lamina propria are the only adult tissues devoid of HSPC-independent resident
      macrophages. Recent investigations have identified that resident macrophages
      originate from the extra-embryonic yolk sac hematopoiesis from progenitor(s)
      distinct from fetal hematopoietic stem cells (HSC). Among yolk sac definitive
      hematopoiesis, erythromyeloid progenitors (EMP) give rise both to erythroid and
      myeloid cells, in particular resident macrophages. EMP are only generated within
      the yolk sac between E8.5 and E10.5 days of development and they migrate to the
      fetal liver as early as circulation is connected, where they expand and
      differentiate until at least E16.5. Their progeny includes erythrocytes,
      macrophages, neutrophils and mast cells but only EMP-derived macrophages persist
      until adulthood in tissues. The transient nature of EMP emergence and the
      temporal overlap with HSC generation renders the analysis of these progenitors
      difficult. We have established a tamoxifen-inducible fate mapping protocol based
      on expression of the macrophage cytokine receptor Csf1r promoter to characterize
      EMP and EMP-derived cells in vivo by flow cytometry.

PMID- 28745621
TI  - Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web.
AB  - We demonstrate the usage of Bio3D-web for the interactive analysis of
      biomolecular structure data. The Bio3D-web application provides online
      functionality for: (1) The identification of related protein structure sets to
      user specified thresholds of similarity; (2) Their multiple alignment and
      structure superposition; (3) Sequence and structure conservation analysis; (4)
      Inter-conformer relationship mapping with principal component analysis, and (5)
      comparison of predicted internal dynamics via ensemble normal mode analysis. This
      integrated functionality provides a complete online workflow for investigating
      sequence-structure-dynamic relationships within protein families and
      superfamilies.

PMID- 28745622
TI  - A Graphical User Interface for Software-assisted Tracking of Protein
      Concentration in Dynamic Cellular Protrusions.
AB  - Filopodia are dynamic, finger-like cellular protrusions associated with migration
      and cell-cell communication. In order to better understand the complex signaling
      mechanisms underlying filopodial initiation, elongation and subsequent
      stabilization or retraction, it is crucial to determine the spatio-temporal
      protein activity in these dynamic structures. To analyze protein function in
      filopodia, we recently developed a semi-automated tracking algorithm that adapts
      to filopodial shape-changes, thus allowing parallel analysis of protrusion
      dynamics and relative protein concentration along the whole filopodial length.
      Here, we present a detailed step-by-step protocol for optimized cell handling,
      image acquisition and software analysis. We further provide instructions for the
      use of optional features during image analysis and data representation, as well
      as troubleshooting guidelines for all critical steps along the way. Finally, we
      also include a comparison of the described image analysis software with other
      programs available for filopodia quantification. Together, the presented protocol
      provides a framework for accurate analysis of protein dynamics in filopodial
      protrusions using image analysis software.

PMID- 28745623
TI  - A Standardized Approach for Multispecies Purification of Mammalian Male Germ
      Cells by Mechanical Tissue Dissociation and Flow Cytometry.
AB  - Fluorescence-activated cell sorting (FACS) has been one of the methods of choice
      to isolate enriched populations of mammalian testicular germ cells. Currently, it
      allows the discrimination of up to 9 murine germ cell populations with high yield
      and purity. This high-resolution in discrimination and purification is possible
      due to unique changes in chromatin structure and quantity throughout
      spermatogenesis. These patterns can be captured by flow cytometry of male germ
      cells stained with fluorescent DNA-binding dyes such as Hoechst-33342 (Hoechst).
      Herein is a detailed description of a recently developed protocol to isolate
      mammalian testicular germ cells. Briefly, single cell suspensions are generated
      from testicular tissue by mechanical dissociation, double stained with Hoechst
      and propidium iodide (PI) and processed by flow cytometry. A serial gating
      strategy, including the selection of live cells (PI negative) with different DNA
      content (Hoechst intensity), is used during FACS sorting to discriminate up to 5
      germ cell types. These include, with corresponding average purities (determined
      by microscopy evaluation): spermatogonia (66%), primary (71%) and secondary (85%)
      spermatocytes, and spermatids (90%), further separated into round (93%) and
      elongating (87%) subpopulations. Execution of the entire workflow is
      straightforward, allows the isolation of 4 cell types simultaneously with the
      appropriate FACS machine, and can be performed in less than 2 h. As reduced
      processing time is crucial to preserve the physiology of ex vivo cells, this
      method is ideal for downstream high-throughput studies of male germ cell biology.
      Moreover, a standardized protocol for multispecies purification of mammalian germ
      cells eliminates methodological sources of variables and allows a single set of
      reagents to be used for different animal models.

PMID- 28745624
TI  - Cardiac Muscle-cell Based Actuator and Self-stabilizing Biorobot - PART 1.
AB  - Biological machines often referred to as biorobots, are living cell- or tissue
      based devices that are powered solely by the contractile activity of living
      components. Due to their inherent advantages, biorobots are gaining interest as
      alternatives to traditional fully artificial robots. Various studies have focused
      on harnessing the power of biological actuators, but only recently studies have
      quantitatively characterized the performance of biorobots and studied their
      geometry to enhance functionality and efficiency. Here, we demonstrate the
      development of a self-stabilizing swimming biorobot that can maintain its pitch,
      depth, and roll without external intervention. The design and fabrication of the
      PDMS scaffold for the biological actuator and biorobot followed by the
      functionalization with fibronectin is described in this first part. In the second
      part of this two-part article, we detail the incorporation of cardiomyocytes and
      characterize the biological actuator and biorobot function. Both incorporate a
      base and tail (cantilever) which produce fin-based propulsion. The tail is
      constructed with soft lithography techniques using PDMS and laser engraving.
      After incorporating the tail with the device base, it is functionalized with a
      cell adhesive protein and seeded confluently with cardiomyocytes. The base of the
      biological actuator consists of a solid PDMS block with a central glass bead
      (acts as a weight). The base of the biorobot consists of two composite PDMS
      materials, Ni-PDMS and microballoon-PDMS (MB-PDMS). The nickel powder (in Ni
      PDMS) allows magnetic control of the biorobot during cells seeding and stability
      during locomotion. Microballoons (in MB-PDMS) decrease the density of MB-PDMS,
      and enable the biorobot to float and swim steadily. The use of these two
      materials with different mass densities, enabled precise control over the weight
      distribution to ensure a positive restoration force at any angle of the biorobot.
      This technique produces a magnetically controlled self-stabilizing swimming
      biorobot.

PMID- 28745625
TI  - A Protocol for Multiple Gene Knockout in Mouse Small Intestinal Organoids Using a
      CRISPR-concatemer.
AB  - CRISPR/Cas9 technology has greatly improved the feasibility and speed of loss-of
      function studies that are essential in understanding gene function. In higher
      eukaryotes, paralogous genes can mask a potential phenotype by compensating the
      loss of a gene, thus limiting the information that can be obtained from genetic
      studies relying on single gene knockouts. We have developed a novel, rapid
      cloning method for guide RNA (gRNA) concatemers in order to create multi-gene
      knockouts following a single round of transfection in mouse small intestinal
      organoids. Our strategy allows for the concatemerization of up to four individual
      gRNAs into a single vector by performing a single Golden Gate shuffling reaction
      with annealed gRNA oligos and a pre-designed retroviral vector. This allows
      either the simultaneous knockout of up to four different genes, or increased
      knockout efficiency following the targeting of one gene by multiple gRNAs. In
      this protocol, we show in detail how to efficiently clone multiple gRNAs into the
      retroviral CRISPR-concatemer vector and how to achieve highly efficient
      electroporation in intestinal organoids. As an example, we show that simultaneous
      knockout of two pairs of genes encoding negative regulators of the Wnt signaling
      pathway (Axin1/2 and Rnf43/Znrf3) renders intestinal organoids resistant to the
      withdrawal of key growth factors.

PMID- 28745626
TI  - Quantifying Branching Density in Rat Mammary Gland Whole-mounts Using the Sholl
      Analysis Method.
AB  - An increasing number of studies are utilizing the rodent mammary gland as an
      endpoint for assessing the developmental toxicity of a chemical exposure. The
      effects these exposures have on mammary gland development are typically evaluated
      using either basic dimensional measurements or by scoring morphological
      characteristics. However, the broad range of methods for interpreting
      developmental changes could lead to inconsistent translations across
      laboratories. A common method of assessment is needed so that proper
      interpretations can be formed from data being compared across studies. The
      present study describes the application of the Sholl analysis method to quantify
      mammary gland branching characteristics. The Sholl method was originally
      developed for use in quantifying neuronal dendritic patterns. By using ImageJ, an
      open-source image analysis software package, and a plugin developed for this
      analysis, the mammary gland branching density and the complexity of a mammary
      gland from a peripubertal female rat were determined. The methods described here
      will enable the use of the Sholl analysis as an effective tool for quantifying an
      important characteristic of mammary gland development.

PMID- 28745627
TI  - Spinal Cord Neurons Isolation and Culture from Neonatal Mice.
AB  - We present a protocol for the isolation and culture of spinal cord neurons. The
      neurons are obtained from neonatal C57BL/6 mice and are isolated on postnatal day
      1-3. A mouse litter, usually 4-10 pups born from one breeding pair, is gathered
      for one experiment, and spinal cords are collected individually from each mouse
      after euthanasia with isoflurane. The spinal column is dissected out and then the
      spinal cord is released from the column. The spinal cords are then minced to
      increase the surface area of delivery for an enzymatic protease that allows for
      the neurons and other cells to be released from the tissue. Trituration is then
      used to release the cells into solution. This solution is subsequently
      fractionated in a density gradient to separate the various cells in solution,
      allowing for neurons to be isolated. Approximately 1-2.5 x 106 neurons can be
      isolated from one litter group. The neurons are then seeded onto wells coated
      with adhesive factors that allow for proper growth and maturation. The neurons
      take approximately 7 days to reach maturity in the growth and culture medium and
      can be used thereafter for treatment and analysis.

PMID- 28745628
TI  - A Method to Test the Effect of Environmental Cues on Mating Behavior in
      Drosophila melanogaster.
AB  - An individual's sexual drive is influenced by genotype, experience and
      environmental conditions. How these factors interact to modulate sexual behaviors
      remains poorly understood. In Drosophila melanogaster, environmental cues, such
      as food availability, affect mating activity offering a tractable system to
      investigate the mechanisms modulating sexual behavior. In D. melanogaster,
      environmental cues are often sensed via the chemosensory gustatory and olfactory
      systems. Here, we present a method to test the effect of environmental chemical
      cues on mating behavior. The assay consists of a small mating arena containing
      food medium and a mating couple. The mating frequency for each couple is
      continuously monitored for 24 h. Here we present the applicability of this assay
      to test environmental compounds from an external source through a pressurized air
      system as well as manipulation of the environmental components directly in the
      mating arena. The use of a pressurized air system is especially useful to test
      the effect of very volatile compounds, while manipulating components directly in
      the mating arena can be of value to ascertain a compound's presence. This assay
      can be adapted to answer questions about the influence of genetic and
      environmental cues on mating behavior and fecundity as well as other male and
      female reproductive behaviors.

PMID- 28745629
TI  - Intrarenal Injection of Escherichia coli in a Rat Model of Pyelonephritis.
AB  - Pyelonephritis is a bacterial infection of the kidney and is most commonly caused
      by Escherichia coli. Recurrent infections can cause significant renal
      inflammation and fibrosis ultimately resulting in declining kidney function.
      Before improved clinical management and prevention of pyelonephritis can be
      instituted, a reliable animal model must be established in order to study the
      mechanisms of progression, recurrence, and therapeutic efficacy. The
      transurethral infection model closely mimics human pyelonephritis but exhibits
      considerable variation due to its reliance on urethral reflux to transport the
      bacteria to the kidney. Herein, a detailed surgical protocol for performing
      bacterial injections into the rat renal pelvis is provided and confirmed by non
      invasive Magnetic Resonance Imaging (MRI). Using this protocol, animals receive
      direct exposure to a desired concentration of E. coli bacteria and can fully
      recover from the surgical procedure with adequate post-operative care. This
      facilitates subsequent longitudinal MRI assessments of the experimental animal
      models for comparison with saline (sham) controls. Using this direct delivery
      approach, the severity of infection is controllable and applicable for
      mechanistic studies of progression as well as development of novel treatment
      strategies.

PMID- 28745630
TI  - Subpial Adeno-associated Virus 9 (AAV9) Vector Delivery in Adult Mice.
AB  - The successful development of a subpial adeno-associated virus 9 (AAV9) vector
      delivery technique in adult rats and pigs has been reported on previously. Using
      subpially-placed polyethylene catheters (PE-10 or PE-5) for AAV9 delivery, potent
      transgene expression through the spinal parenchyma (white and gray matter) in
      subpially-injected spinal segments has been demonstrated. Because of the wide
      range of transgenic mouse models of neurodegenerative diseases, there is a strong
      desire for the development of a potent central nervous system (CNS)-targeted
      vector delivery technique in adult mice. Accordingly, the present study describes
      the development of a spinal subpial vector delivery device and technique to
      permit safe and effective spinal AAV9 delivery in adult C57BL/6J mice. In
      spinally immobilized and anesthetized mice, the pia mater (cervical 1 and lumbar
      1-2 spinal segmental level) was incised with a sharp 34 G needle using an XYZ
      manipulator. A second XYZ manipulator was then used to advance a blunt 36G needle
      into the lumbar and/or cervical subpial space. The AAV9 vector (3-5 uL; 1.2 x
      1013 genome copies (gc)) encoding green fluorescent protein (GFP) was then
      injected subpially. After injections, neurological function (motor and sensory)
      was assessed periodically, and animals were perfusion-fixed 14 days after AAV9
      delivery with 4% paraformaldehyde. Analysis of horizontal or transverse spinal
      cord sections showed transgene expression throughout the entire spinal cord, in
      both gray and white matter. In addition, intense retrogradely-mediated GFP
      expression was seen in the descending motor axons and neurons in the motor
      cortex, nucleus ruber, and formatio reticularis. No neurological dysfunction was
      noted in any animals. These data show that the subpial vector delivery technique
      can successfully be used in adult mice, without causing procedure-related spinal
      cord injury, and is associated with highly potent transgene expression throughout
      the spinal neuraxis.

PMID- 28745631
TI  - Integration of Miniaturized Solid Phase Extraction and LC-MS/MS Detection of 3
      Nitrotyrosine in Human Urine for Clinical Applications.
AB  - Free 3-nitrotyrosine (3-NT) has been extensively used as a possible biomarker for
      oxidative stress. Increased levels of 3-NT have been reported in a wide variety
      of pathological conditions. However, existing methods lack the sufficient
      sensitivity and/or specificity necessary to measure the low endogenous level of 3
      NT reliably and are too cumbersome for clinical applications. Hence, analytical
      improvement is urgently needed to accurately quantify the levels of 3-NT and
      verify the role of 3-NT in pathological conditions. This protocol presents the
      development of a novel liquid chromatography tandem mass spectrometry (LC-MS/MS)
      detection combined with a miniaturized solid phase extraction (SPE) for the rapid
      and accurate measurement of 3-NT in human urine as a non-invasive biomarker for
      oxidative stress. SPE using a 96-well plate markedly simplified the process by
      combining sample cleanup and analyte enrichment without tedious derivatization
      and evaporation steps, reducing solvent consumption, waste disposal, risk of
      contamination and overall processing time. The employment of 25 mM ammonium
      acetate (NH4OAc) at pH 9 as the SPE elution solution substantially enhanced the
      selectivity. Mass spectrometry signal response was improved through adjustment of
      the multiple reaction monitoring (MRM) transitions. Use of 0.01% HCOOH as
      additive on a pentafluorophenyl (PFP) column (150 mm x 2.1 mm, 3 um) improved
      signal response another 2.5-fold and shortened the overall run time to 7 min. A
      lower limit of quantitation (LLOQ) of 10 pg/mL (0.044 nM) was achieved,
      representing a significant sensitivity improvement over the reported assays. This
      simplified, rapid, selective and sensitive method allows two plates of urine
      samples (n = 192) to be processed in a 24 h time-period. Considering the markedly
      improved analytical performance, and non-invasive and inexpensive urine sampling,
      the proposed assay is beneficial for pre-clinical and clinical studies.

PMID- 28745632
TI  - Differentiating Chondrocytes from Peripheral Blood-derived Human Induced
      Pluripotent Stem Cells.
AB  - In this study, we used peripheral blood cells (PBCs) as seed cells to produce
      chondrocytes via induced pluripotent stem cells (iPSCs) in an integration-free
      method. Following embryoid body (EB) formation and fibroblastic cell expansion,
      the iPSCs are induced for chondrogenic differentiation for 21 days under serum
      free and xeno-free conditions. After chondrocyte induction, the phenotypes of the
      cells are evaluated by morphological, immunohistochemical, and biochemical
      analyses, as well as by the quantitative real-time PCR examination of
      chondrogenic differentiation markers. The chondrogenic pellets show positive
      alcian blue and toluidine blue staining. The immunohistochemistry of collagen II
      and X staining is also positive. The sulfated glycosaminoglycan (sGAG) content
      and the chondrogenic differentiation markers COLLAGEN 2 (COL2), COLLAGEN 10
      (COL10), SOX9, and AGGRECAN are significantly upregulated in chondrogenic pellets
      compared to hiPSCs and fibroblastic cells. These results suggest that PBCs can be
      used as seed cells to generate iPSCs for cartilage repair, which is patient
      specific and cost-effective.

PMID- 28745633
TI  - Determination of the Glycogen Content in Cyanobacteria.
AB  - Cyanobacteria accumulate glycogen as a major intracellular carbon and energy
      storage during photosynthesis. Recent developments in research have highlighted
      complex mechanisms of glycogen metabolism, including the diel cycle of
      biosynthesis and catabolism, redox regulation, and the involvement of non-coding
      RNA. At the same time, efforts are being made to redirect carbon from glycogen to
      desirable products in genetically engineered cyanobacteria to enhance product
      yields. Several methods are used to determine the glycogen contents in
      cyanobacteria, with variable accuracies and technical complexities. Here, we
      provide a detailed protocol for the reliable determination of the glycogen
      content in cyanobacteria that can be performed in a standard life science
      laboratory. The protocol entails the selective precipitation of glycogen from the
      cell lysate and the enzymatic depolymerization of glycogen to generate glucose
      monomers, which are detected by a glucose oxidase-peroxidase (GOD-POD) enzyme
      coupled assay. The method has been applied to Synechocystis sp. PCC 6803 and
      Synechococcus sp. PCC 7002, two model cyanobacterial species that are widely used
      in metabolic engineering. Moreover, the method successfully showed differences in
      the glycogen contents between the wildtype and mutants defective in regulatory
      elements or glycogen biosynthetic genes.

PMID- 28745634
TI  - Synthesis and Testing of Supported Pt-Cu Solid Solution Nanoparticle Catalysts
      for Propane Dehydrogenation.
AB  - A convenient method for the synthesis of bimetallic Pt-Cu catalysts and
      performance tests for propane dehydrogenation and characterization are
      demonstrated here. The catalyst forms a substitutional solid solution structure,
      with a small and uniform particle size around 2 nm. This is realized by careful
      control over the impregnation, calcination, and reduction steps during catalyst
      preparation and is identified by advanced in situ synchrotron techniques. The
      catalyst propane dehydrogenation performance continuously improves with
      increasing Cu:Pt atomic ratio.

PMID- 28745635
TI  - A Practical Guide on Coupling a Scanning Mobility Sizer and Inductively Coupled
      Plasma Mass Spectrometer (SMPS-ICPMS).
AB  - A large variety of analytical methods are available to characterize particles in
      aerosols and suspensions. The choice of the appropriate technique depends on the
      properties to be determined. In many fields information about particle size and
      chemical composition are of great importance. While in aerosol techniques
      particle size distributions of gas-borne particles are determined online, their
      elemental composition is commonly analyzed offline after an appropriate sampling
      and preparation procedure. To obtain both types of information online and
      simultaneously, a hyphenated setup was recently developed, including a Scanning
      Mobility Particle Sizer (SMPS) and an Inductively Coupled Plasma Mass
      Spectrometer (ICPMS). This allows first to classify the particles with respect to
      their mobility diameter, and then to determine their number concentration and
      elemental composition in parallel. A Rotating Disk Diluter (RDD) is used as the
      introduction system, giving more flexibility regarding the use of different
      aerosol sources. In this work, a practical guide is provided describing the
      different steps for establishing this instrumentation, and how to use this
      analysis tool. The versatility of this hyphenated technique is demonstrated in
      example measurements on three different aerosols generated out of a) a salt
      solution, b) a suspension, and c) emitted by a thermal process.

PMID- 28745636
TI  - 20 mJ, 1 ps Yb:YAG Thin-disk Regenerative Amplifier.
AB  - This is a report on a 100 W, 20 mJ, 1 ps Yb:YAG thin-disk regenerative amplifier.
      A homemade Yb:YAG thin-disk, Kerr-lens mode-locked oscillator with turn-key
      performance and microjoule-level pulse energy is used to seed the regenerative
      chirped-pulse amplifier. The amplifier is placed in airtight housing. It operates
      at room temperature and exhibits stable operation at a 5 kHz repetition rate,
      with a pulse-to-pulse stability less than 1%. By employing a 1.5 mm-thick beta
      barium borate crystal, the frequency of the laser output is doubled to 515 nm,
      with an average power of 70 W, which corresponds to an optical-to-optical
      efficiency of 70%. This superior performance makes the system an attractive pump
      source for optical parametric chirped-pulse amplifiers in the near-infrared and
      mid-infrared spectral range. Combining the turn-key performance and the superior
      stability of the regenerative amplifier, the system facilitates the generation of
      a broadband, CEP-stable seed. Providing the seed and pump of the optical
      parametric chirped-pulse amplification (OPCPA) from one laser source eliminates
      the demand of active temporal synchronization between these pulses. This work
      presents a detailed guide to set up and operate a Yb:YAG thin-disk regenerative
      amplifier, based on chirped-pulse amplification (CPA), as a pump source for an
      optical parametric chirped-pulse amplifier.

PMID- 28745637
TI  - Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal
      Cancer.
AB  - Despite the advantages of easy applicability and cost-effectiveness, subcutaneous
      mouse models have severe limitations and do not accurately simulate tumor biology
      and tumor cell dissemination. Orthotopic mouse models have been introduced to
      overcome these limitations; however, such models are technically demanding,
      especially in hollow organs such as the large bowel. In order to produce uniform
      tumors which reliably grow and metastasize, standardized techniques of tumor cell
      preparation and injection are critical. We have developed an orthotopic mouse
      model of colorectal cancer (CRC) which develops highly uniform tumors and can be
      used for tumor biology studies as well as therapeutic trials. Tumor cells from
      either primary tumors, 2-dimensional (2D) cell lines or 3-dimensional (3D)
      organoids are injected into the cecum and, depending on the metastatic potential
      of the injected tumor cells, form highly metastatic tumors. In addition, CTCs can
      be found regularly. We here describe the technique of tumor cell preparation from
      both 2D cell lines and 3D organoids as well as primary tumor tissue, the surgical
      and injection techniques as well as the isolation of CTCs from the tumor-bearing
      mice, and present tips for troubleshooting.

PMID- 28745638
TI  - Localization of Odorant Receptor Genes in Locust Antennae by RNA In Situ
      Hybridization.
AB  - Insects have evolved sophisticated olfactory reception systems to sense exogenous
      chemical signals. These chemical signals are transduced by Olfactory Receptor
      Neurons (ORNs) housed in hair-like structures, called chemosensilla, of the
      antennae. On the ORNs' membranes, Odorant Receptors (ORs) are believed to be
      involved in odor coding. Thus, being able to identify genes localized to the ORNs
      is necessary to recognize OR genes, and provides a fundamental basis for further
      functional in situ studies. The RNA expression levels of specific ORs in insect
      antennae are very low, and preserving insect tissue for histology is challenging.
      Thus, it is difficult to localize an OR to a specific type of sensilla using RNA
      in situ hybridization. In this paper, a detailed and highly effective RNA in situ
      hybridization protocol particularly for lowly expressed OR genes of insects, is
      introduced. In addition, a specific OR gene was identified by conducting double
      color fluorescent in situ hybridization experiments using a co-expressing
      receptor gene, Orco, as a marker.

PMID- 28745639
TI  - A Lipid Extraction and Analysis Method for Characterizing Soil Microbes in
      Experiments with Many Samples.
AB  - Microbial communities are important drivers and regulators of ecosystem
      processes. To understand how management of ecosystems may affect microbial
      communities, a relatively precise but effort-intensive technique to assay
      microbial community composition is phospholipid fatty acid (PLFA) analysis. PLFA
      was developed to analyze phospholipid biomarkers, which can be used as indicators
      of microbial biomass and the composition of broad functional groups of fungi and
      bacteria. It has commonly been used to compare soils under alternative plant
      communities, ecology, and management regimes. The PLFA method has been shown to
      be sensitive to detecting shifts in microbial community composition. An
      alternative method, fatty acid methyl ester extraction and analysis (MIDI-FA) was
      developed for rapid extraction of total lipids, without separation of the
      phospholipid fraction, from pure cultures as a microbial identification
      technique. This method is rapid but is less suited for soil samples because it
      lacks an initial step separating soil particles and begins instead with a
      saponification reaction that likely produces artifacts from the background
      organic matter in the soil. This article describes a method that increases
      throughput while balancing effort and accuracy for extraction of lipids from the
      cell membranes of microorganisms for use in characterizing both total lipids and
      the relative abundance of indicator lipids to determine soil microbial community
      structure in studies with many samples. The method combines the accuracy achieved
      through PLFA profiling by extracting and concentrating soil lipids as a first
      step, and a reduction in effort by saponifying the organic material extracted and
      processing with the MIDI-FA method as a second step.

PMID- 28745640
TI  - Determination of Sialic Acids in Liver and Milk Samples of Wild-type and CMAH
      Knock-out Mice.
AB  - CMAH (cytidine monophosphate-N-acetylneuraminic acid hydroxylase) is responsible
      for the oxidation of cytidine monophosphate-N-acetylneuraminic acids in mammals.
      However, humans cannot oxidize cytidine monophosphate-N-acetylneuraminic acid to
      cytidine monophosphate-N-glycolylneuraminic acid due to a primary exon deletion
      of the CMAH gene. To understand the effects and implications of the lack of CMAH
      activity in more detail, a Cmah knock-out model in mice is of keen interest in
      basic and applied research. The analysis method to determine the phenotype of
      this mouse model is herein described in detail, and is based on the detection of
      both N-acetylneuraminic acid and N-glycolylenuraminic acid in the liver and milk
      of wild-type and Cmah knock-out mice. Endogenous sialic acids are released and
      derivatized with o-phenylenediamine to generate fluorogenic derivatives, which
      can be subsequently analyzed by HPLC. The presented protocol can be also applied
      for the analysis of milk and tissue samples from various other origins, and may
      be of use to investigate the nutritional and health effects of N
      glycolylneuraminic acid.

PMID- 28745641
TI  - Automated Analysis of a Nematode Population-based Chemosensory Preference Assay.
AB  - The nematode, Caenorhabditis elegans' compact nervous system of only 302 neurons
      underlies a diverse repertoire of behaviors. To facilitate the dissection of the
      neural circuits underlying these behaviors, the development of robust and
      reproducible behavioral assays is necessary. Previous C. elegans behavioral
      studies have used variations of a "drop test", a "chemotaxis assay", and a
      "retention assay" to investigate the response of C. elegans to soluble compounds.
      The method described in this article seeks to combine the complementary strengths
      of the three aforementioned assays. Briefly, a small circle in the middle of each
      assay plate is divided into four quadrants with the control and experimental
      solutions alternately placed. After the addition of the worms, the assay plates
      are loaded into a behavior chamber where microscope cameras record the worms'
      encounters with the treated regions. Automated video analysis is then performed
      and a preference index (PI) value for each video is generated. The video
      acquisition and automated analysis features of this method minimizes the
      experimenter's involvement and any associated errors. Furthermore, minute amounts
      of the experimental compound are used per assay and the behavior chamber's multi
      camera setup increases experimental throughput. This method is particularly
      useful for conducting behavioral screens of genetic mutants and novel chemical
      compounds. However, this method is not appropriate for studying stimulus gradient
      navigation due to the close proximity of the control and experimental solution
      regions. It should also not be used when only a small population of worms is
      available. While suitable for assaying responses only to soluble compounds in its
      current form, this method can be easily modified to accommodate multimodal
      sensory interaction and optogenetic studies. This method can also be adapted to
      assay the chemosensory responses of other nematode species.

PMID- 28745642
TI  - Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury
      Using a Radial Water Tread Maze.
AB  - Despite the recent increase in use of mouse models in scientific research,
      researchers continue to use cognitive tasks that were originally designed and
      validated for rat use. The Radial Water Tread (RWT) maze test of spatial memory
      (designed specifically for mice and requiring no swimming) has been shown
      previously to successfully distinguish between controlled cortical impact-induced
      TBI mice and sham controls. Here, a detailed protocol for this task is presented.
      The RWT maze capitalizes on the natural tendency of mice to avoid open areas in
      favor of hugging the sides of an apparatus (thigmotaxis). The walls of the maze
      are lined with nine escape holes placed above the floor of the apparatus, and
      mice are trained to use visual cues to locate the escape hole that leads out of
      the maze. The maze is filled with an inch of cold water, sufficient to motivate
      escape but not deep enough to require that the mouse swim. The acquisition period
      takes only four training days, with a test of memory retention on day five and a
      long-term memory test on day 12. The results reported here suggest that the RWT
      maze is a feasible alternative to rat-validated, swimming-based cognitive tests
      in the assessment of spatial memory deficits in mouse models of TBI.

PMID- 28745643
TI  - Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult
      Mouse Skin.
AB  - The keratinocyte (KC) is the predominant cell type in the epidermis, the
      outermost layer of the skin. Epidermal KCs play a critical role in providing skin
      defense by forming an intact skin barrier against environmental insults, such as
      UVB irradiation or pathogens, and also by initiating an inflammatory response
      upon those insults. Here we describe methods to isolate KCs from neonatal mouse
      skin and from adult mouse tail skin. We also describe culturing conditions using
      defined growth supplements (dGS) in comparison to chelexed fetal bovine serum
      (cFBS). Functionally, we show that both neonatal and adult KCs are highly
      responsive to high calcium-induced terminal differentiation, tight junction
      formation and stratification. Additionally, cultured adult KCs are susceptible to
      UVB-triggered cell death and can release large amounts of TNF upon UVB
      irradiation. Together, the methods described here will be useful to researchers
      for the setup of in vitro models to study epidermal biology in the neonatal mouse
      and/or the adult mouse.

PMID- 28745644
TI  - Profiling Anti-Neu5Gc IgG in Human Sera with a Sialoglycan Microarray Assay.
AB  - Cells are covered with a cloak of carbohydrate chains (glycans) that is commonly
      altered in cancer and that includes variations in sialic acid (Sia) expression.
      These are acidic sugars that have a 9-carbon backbone and that cap vertebrate
      glycans on cell surfaces. Two of the major Sia forms in mammals are N
      acetylneuraminic acid (Neu5Ac) and its hydroxylated form, N-glycolylneuraminic
      acid (Neu5Gc). Humans cannot produce endogenous Neu5Gc due to the inactivation of
      the gene encoding cytidine 5'monophosphate-Neu5Ac (CMP-Neu5Ac) hydroxylase
      (CMAH). Foreign Neu5Gc is acquired by human cells through the dietary consumption
      of red meat and dairy and subsequently appears on diverse glycans on the cell
      surface, accumulating mostly on carcinomas. Consequently, humans have circulating
      anti-Neu5Gc antibodies that play diverse roles in cancer and other chronic
      inflammation-mediated diseases and that are becoming potential diagnostic and
      therapeutic targets. Here, we describe a high-throughput sialoglycan microarray
      assay to assess such anti-Neu5Gc antibodies in the human sera. Neu5Gc-containing
      glycans and their matched pairs of controls (Neu5Ac-containing glycans), each
      with a core primary amine, are covalently linked to epoxy-coated glass slides. We
      exemplify the printing of 56 slides in a 16-well format using a specific nano
      printer capable of generating up to 896 arrays per print. Each slide can be used
      to screen 16 different human sera samples for the evaluation of anti-Neu5Gc
      antibody specificity, intensity, and diversity. The protocol describes the
      complexity of this robust tool and provides a basic guideline for those aiming to
      investigate the response to Neu5Gc dietary carbohydrate antigen in diverse
      clinical samples in an array format.

PMID- 28745645
TI  - A Simple Neuronal Mechanical Injury Methodology to Study Drosophila Motor Neuron
      Degeneration.
AB  - The degeneration of neurons occurs during normal development and in response to
      injury, stress, and disease. The cellular hallmarks of neuronal degeneration are
      remarkably similar in humans and invertebrates as are the molecular mechanisms
      that drive these processes. The fruit fly, Drosophila melanogaster, provides a
      powerful yet simple genetic model organism to study the cellular complexities of
      neurodegenerative diseases. In fact, approximately 70% of disease-associated
      human genes have a Drosophila homolog and a plethora of tools and assays have
      been described using flies to study human neurodegenerative diseases. More
      specifically the neuromuscular junction (NMJ) in Drosophila has proven to be an
      effective system to study neuromuscular diseases because of the ability to
      analyze the structural connections between the neuron and the muscle. Here, we
      report on an in vivo motor neuron injury assay in Drosophila, which reproducibly
      induces neurodegeneration at the NMJ by 24 h. Using this methodology, we have
      described a temporal sequence of cellular events resulting in motor neuron
      degeneration. The injury method has diverse applications and has also been
      utilized to identify specific genes required for neurodegeneration and to dissect
      transcriptional responses to neuronal injury.

PMID- 28745646
TI  - Reducing State Anxiety Using Working Memory Maintenance.
AB  - The purpose of this protocol is to explain how to examine the relationship
      between working memory processes and anxiety by combining the Sternberg Working
      Memory (WM) and the threat of shock paradigms. In the Sternberg WM paradigm,
      subjects are required to maintain a series of letters in the WM for a brief
      interval and respond by identifying whether the position of a given letter in the
      series matches a numerical prompt. In the threat of shock paradigm, subjects are
      exposed to alternating blocks where they are either at risk of receiving
      unpredictable presentations of a mild electric shock or are safe from the shock.
      Anxiety is probed throughout the safe and threat blocks using the acoustic
      startle reflex, which is potentiated under threat (Anxiety-Potentiated Startle
      (APS)). By conducting the Sternberg WM paradigm during the threat of shock and
      probing the startle response during either the WM maintenance interval or the
      intertrial interval, it is possible to determine the effect of WM maintenance on
      APS.

PMID- 28745647
TI  - Utilization of Capsules for Negative Staining of Viral Samples within
      Biocontainment.
AB  - Transmission electron microscopy (TEM) is used to observe the ultrastructure of
      viruses and other microbial pathogens with nanometer resolution. Most biological
      materials do not contain dense elements capable of scattering electrons to create
      an image; therefore, a negative stain, which places dense heavy metal salts
      around the sample, is required. In order to visualize viruses in suspension under
      the TEM they must be applied to small grids coated with a transparent surface
      only nanometers thick. Due to their small size and fragility, these grids are
      difficult to handle and easily moved by air currents. The thin surface is easily
      damaged, leaving the sample difficult or impossible to image. Infectious viruses
      must be handled in a biosafety cabinet (BSC) and some require a biocontainment
      laboratory environment. Staining viruses in biosafety levels (BSL)-3 and -4 is
      especially challenging because these environments are more turbulent and
      technicians are required to wear personal protective equipment (PPE), which
      decreases dexterity. In this study, we evaluated a new device to assist in
      negative staining viruses in biocontainment. The device is a capsule that works
      as a specialized pipette tip. Once grids are loaded into the capsule, the user
      simply aspirates reagents into the capsule to deliver the virus and stains to the
      encapsulated grid, thus eliminating user handling of grids. Although this
      technique was designed specifically for use in BSL-3 or -4 biocontainment, it can
      ease sample preparation in any lab environment by enabling easy negative staining
      of virus. This same method can also be applied to prepare negative stained TEM
      specimens of nanoparticles, macromolecules and similar specimens.

PMID- 28745648
TI  - Fizzy Extraction of Volatile Organic Compounds Combined with Atmospheric Pressure
      Chemical Ionization Quadrupole Mass Spectrometry.
AB  - Chemical analysis of volatile and semivolatile compounds dissolved in liquid
      samples can be challenging. The dissolved components need to be brought to the
      gas phase, and efficiently transferred to a detection system. Fizzy extraction
      takes advantage of the effervescence phenomenon. First, a carrier gas (here,
      carbon dioxide) is dissolved in the sample by applying overpressure and stirring
      the sample. Second, the sample chamber is decompressed abruptly. Decompression
      leads to the formation of numerous carrier gas bubbles in the sample liquid.
      These bubbles assist the release of the dissolved analyte species from the liquid
      to the gas phase. The released analytes are immediately transferred to the
      atmospheric pressure chemical ionization interface of a triple quadrupole mass
      spectrometer. The ionizable analyte species give rise to mass spectrometric
      signals in the time domain. Because the release of the analyte species occurs
      over short periods of time (a few seconds), the temporal signals have high
      amplitudes and high signal-to-noise ratios. The amplitudes and areas of the
      temporal peaks can then be correlated with concentrations of the analytes in the
      liquid samples subjected to fizzy extraction, which enables quantitative
      analysis. The advantages of fizzy extraction include: simplicity, speed, and
      limited use of chemicals (solvents).

PMID- 28745649
TI  - High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism
      Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility
      Assessment.
AB  - Complement receptor 1 (CR1), a transmembrane glycoprotein that plays a key role
      in the innate immune system, is expressed on many cell types, but especially on
      red blood cells (RBCs). As a receptor for the complement components C3b and C4b,
      CR1 regulates the activation of the complement cascade and promotes the
      phagocytosis of immune complexes and cellular debris, as well as the amyloid-beta
      (Abeta) peptide in Alzheimer's disease (AD). Several studies have confirmed AD
      associated single nucleotide polymorphisms (SNPs), as well as a copy-number
      variation (CNV) in the CR1 gene. Here, we describe an innovative method for
      determining the length polymorphism of the CR1 receptor. The receptor includes
      three domains, called long homologous repeats (LHR)-LHR-A, LHR-C, and LHR-D-and
      an n domain, LHR-B, where n is an integer between 0 and 3. Using a single pair of
      specific primers, the genetic material is used to amplify a first fragment of the
      LHR-B domain (the variant amplicon B) and a second fragment of the LHR-C domain
      (the invariant amplicon). The variant amplicon B and the invariant amplicon
      display differences at five nucleotides outside of the hybridization areas of
      said primers. The numbers of variant amplicons B and of invariant amplicons is
      deduced using a quantitative tool (high-resolution melting (HRM) curves), and the
      ratio of the variant amplicon B to the invariant amplicon differs according to
      the CR1 length polymorphism. This method provides several advantages over the
      canonical phenotype method, as it does not require fresh material and is cheaper,
      faster, and therefore applicable to larger populations. Thus, the use of this
      method should be helpful to better understand the role of CR1 isoforms in the
      pathogenesis of diseases such as AD.

PMID- 28745650
TI  - [Comparative analysis of corneal aberrations after intrastromal segments and
      MyoRing implantation using femtosecond laser in patients with keratoconus].
AB  - AIM: to comparatively analyze corneal aberrations after intrastromal corneal
      segments (ICS) and MyoRing implantation using femtosecond laser in patients with
      stage II-III keratoconus (KC) by Pentacam examination. MATERIAL AND METHODS: We
      have operated on 135 patients (145 eyes) with stage II or III KC. Depending on
      surgical technique, all patients were divided into two groups. Group I consisted
      of patients with KC, who received optimized femtosecond laser-assisted MyoRing
      implantation, group II - of those, who received femtosecond laser-assisted ICS
      implantation. Depending on the stage of the disease, each group was further
      divided into two subgroups, for stage II and stage III KC, respectively. Before
      and after surgery, all patients underwent visometry, biomicroscopy, corneal
      topography, and corneal aberrations measurement under photopic and mesopic
      conditions on Pentacam. The follow-up period averaged 30 months (from 6 to 34
      months). RESULTS: In both groups corneal aberrations significantly decreased
      after surgery, which was confirmed by an improvement in parameters of refraction
      and keratometry readings. CONCLUSION: Implantation of intrastromal MyoRings leads
      to a greater reduction in the total corneal aberration, higher-order aberrations
      under photopic and mesopic conditions, and spherical aberration under photopic
      conditions as compared to ICS in patients with stage III KC; a comparable
      reduction in the total corneal, higher-order, and spherical aberrations under
      photopic conditions as compared to ICS in patients with stage II KC; a comparable
      increase in spherical aberration under mesopic conditions as compared to ICS in
      patients with stage III KC.

PMID- 28745651
TI  - [Studying the association between genetic polymorphism of growth factors and the
      development of primary open-angle glaucoma].
AB  - : Primary open-angle glaucoma (POAG) is a multifactorial disease,
      etiopathogenesis of which largely depends on growth factors. Possessing a variety
      of medical and biological effects, these cytokines may influence the development
      and progression of POAG. AIM: to reveal the role of genetic polymorphisms of
      growth factors in predisposition to developing POAG that is refractory to local
      hypotensive therapy. MATERIAL AND METHODS: The object of the study were 162
      patients with stage II-III POAG, in whom local hypotensive therapy was
      inefficient, 90 patients with stage II-III POAG well controlled on local
      hypotensive therapy, and 191 controls. The material for the study was venous
      blood taken from the cubital vein of a proband. Isolation of genomic DNA was
      performed by phenol-chloroform extraction. Analysis of genetic polymorphisms of
      growth factors was performed through allelic discrimination. For that, synthesis
      of DNA was carried out via polymerase chain reaction (PCR). RESULTS: It is found
      that the T IGFR-1 genetic variant (OR=1.34) and a combination of the C VEGF-A and
      T IGFR-1 genetic variants (OR=1.90) are risk factors of developing POAG that is
      refractory to local hypotensive therapy. A statistical model for predicting such
      a risk has been proposed that includes: VEGF-A s.-958C>T genetic marker (rs
      833,061), age, concomitant non-inflammatory ocular diseases, microvascular
      changes in the conjunctiva, the degree of pigmentation of the angle of the
      anterior chamber, and pseudoexfoliative syndrome. Recognition accuracy of the
      model is 90.42%. CONCLUSION: The T IGFR-1 genetic variant and a combination of
      the C VEGF-A and T IGFR-1 genetic variants increase the risk of developing POAG
      that is refractory to local hypotensive therapy.

PMID- 28745652
TI  - [Microcirculatory blood and lymph flow examination in eyelid skin by laser
      Doppler flowmetry].
AB  - AIM: to study normal blood and lymph microcirculation of the upper and lower
      eyelids in different age groups. MATERIAL AND METHODS: The study included 108
      volunteers (216 eyes) aged from 20 to 80 years with no signs of changes in
      anterior segment structures, who were grouped by age ranges (20-30 years, 31-40
      years, 41-50 years, 51-60 years, 61-70 years, and 71-80 years) into 6 groups
      equal in gender and quantitative composition. In all volunteers, microcirculation
      of the upper and lower eyelids was examined by laser Doppler flowmetry (LDF)
      ('LASMA MC-1' peripheral blood and lymph flow analyzer and 'LASMA MC' laser
      diagnostic complex, LASMA LLC). The average perfusion changes in blood and lymph
      flow as well as blood and lymph flow oscillations were analyzed. RESULTS: Blood
      and lymph flow in the microvasculature of the upper and lower eyelids is variable
      and depends on neither the age, nor gender of the test subject. On LDF-gram,
      every increase in amplitude of blood flow corresponds to a decrease in that of
      lymph flow. CONCLUSION: The non-invasive method of LDF expands our diagnostic
      capabilities as it enables assessment of not only blood, but also lymph flow. The
      data obtained can serve as a starting point for exploring microcirculation in
      different age groups in the presence of different pathological processes.

PMID- 28745653
TI  - [Electrophysiological studies of the retina in antiphospholipid syndrome].
AB  - AIM: to evaluate the functional state of the retina in patients with
      antiphospholipid syndrome (APS) through different types of electroretinography
      (ERG). MATERIAL AND METHODS: The total ERG (t-ERG), local macular ERG (m-ERG),
      and oscillatory potentials (OP) were recorded in 56 patients with verified APS.
      RESULTS: In most patients with APS, ERG was of abnormal appearance, particularly,
      t-ERG was notable for reliably lower a- and b-wave amplitudes (70% of cases), m
      ERG - for lower amplitudes and shorter latency (64% of cases). Pathological
      changes of t-ERG and m-ERG components were equally common in patients with and
      without retinal vascular occlusions. Linear dependence was established between
      the decrease in b-wave amplitude of subnormal t-ERG and the Vs value in the
      central retinal artery. A decrease in the OP index and OP configuration
      distortion were found in 82% of patients. At that, OP indices tended to be lower
      in patients from the retinal vascular occlusions group. CONCLUSION: The use of
      different types of ERG enable detection of not only local, but also generalized
      retinal changes in APS. Regardless of the presence of retinal occlusion, APS
      patients show suppression of biopotential in most of cellular elements of the
      retina due to ischemia. Despite high visual acuity, the local macular potential
      gets significantly reduced in more than half of APS patients. Oscillatory
      potentials recording is a highly sensitive method for diagnosis of retinal
      ischmia in APS.

PMID- 28745654
TI  - [Analysis of corneal biomechanical changes after femtosecond laser-assisted laser
      in situ keratomileusis in children with hyperopic anisometropia].
AB  - AIM: to analyze corneal hysteresis (CH) and corneal resistance factor (RF)
      readings obtained with the Reichert Ocular Response Analyzer (ORA) before and
      after hyperopic femtolaser-assisted laser in situ keratomileusis (FS-LASIK) in
      children with anisometropia as well as to establish factors that may cause
      changes in these parameters. MATERIAL AND METHODS: CH and RF were evaluated
      before and 1.5 years after FS-LASIK performed on amblyopic eyes of 28 patients
      aged 6-14 years. Preoperatively, there was a correlation between CH and RF
      (r=0.41, p=0.03). No correlation was found between CH and age (r=-0.02, p=0.82)
      or between CH (r=0.00, p=0.98), RF (r=0.04, p=0.83), and cornea thickness.
      RESULTS: The mean preoperative CH was 12.56+/-1.21 mmHg, RF 12.31+/-1.57 mmHg.
      Postoperatively, a statistically significant change occurred to both CH (by
      0.97+/-1.51 mmHg, p=0.002) and RF (by 1.42+/-1.55 mmHg, p=0.000). No correlation
      was found between CH before and after surgery (r=0.11, p=0.57) as well as between
      the ablation depth and changes in CH (r=0,04, p=0.83) and RF (r=0.21, p=0.28).
      Regression analysis showed that the extent of CH (r2=0.52, p=0.00) and RF
      (r2=0,48, p=0.00) changes was closely related to their preoperative values.
      CONCLUSION: The statistically significant relative change in CH and RF after
      hyperopic FS-LASIK was 8% and 12%, respectively. CH and RF changes correlated
      with their preoperative values, but not with the ablation depth or cornea
      thickness.

PMID- 28745655
TI  - [Significance of anti-myelin basic protein antibodies for ocular hydrodynamic
      disturbances in primary open-angle glaucoma].
AB  - The aim of the study was to investigate the significance of anti-myelin basic
      protein (MBP) antibodies (AB) for ocular hydrodynamic disturbances in primary
      open-angle glaucoma (POAG). The study was conducted using the enzyme-linked
      immunosorbent assay (ELISA). The patients included had either high-tension (82
      cases), or normal-tension (62 patients) glaucoma (HTG and NTG). In 46.3% of HTG
      patients and 38.7% of NTG patients, anti-MBP antibodies were lower than in the
      controls. There were also some cases (12.9%) of increased AB production at NTG
      onset. According to the canons of immunology, a decrease in anti-MBP antibodies
      can be explained by their binding to the protein and an increase - by stimulation
      of AB production through antigen release. In other words, antigen release must
      precede an increase in antibodies, which, in turn, must be followed by a
      subsequent decrease. In this aspect, an increase in anti-MBP antibody production
      at the stage of early hydrodynamic disturbances (NTG) and its decrease at the
      stage of pronounced changes (HTG) are perfectly natural. The level of anti-MBP
      antibodies correlated with the following indicators of ocular hydrodynamics:
      aqueous humor secretion (r=0.20841, p<0.05), intraocular pressure (r=-0.24046,
      r<0.05), ease of outflow (r=-0, 21552; r<0.05), and Becker's coefficient that
      reflects dissociation of control mechanisms in the regulation of hydrodynamics
      (r=-0.21683, p<0.05). The authors came to the conclusion that catalytic
      antibodies to MBP (also able to cause destruction of the myelin sheath of axons)
      play an important role in the pathogenesis of open-angle glaucoma. A decrease as
      well as an increase in anti-MBP antibodies has an unfavorable effect on ocular
      hydrodynamics. A theory has been put forward that these disorders may be induced
      by demyelination of peripheral nervous system axons involved in the regulation of
      intraocular fluid secretion and outflow.

PMID- 28745656
TI  - [Effect of medicinal treatment on epithelial wound healing after
      phacoemulsification].
AB  - AIM: to compare the dynamics of epithelial wound healing under two different post
      op treatments in patients after uncomplicated phacoemulsification. MATERIAL AND
      METHODS: This prospective randomized clinical trial included 40 eyes of 40
      patients aged 66.4+/-8.2 years who underwent uncomplicated phacoemulsification
      with flexible intraocular lens implantation through a 2.2-mm corneal incision.
      Patients were randomized to receive either dexamethasone 0.1% and diclofenac 0.1%
      (n=20 eyes, Group I), or bromfenac 0.09% (n=20 eyes, Group II). Also, all
      patients instilled levofloxacin 0.5%. The dynamics of epithelial wound healing
      was assessed with the RTVue-100 spectral domain optical coherence tomograph with
      CAM-L corneal module in the 3D CORNEA mode 2 hours after surgery and on days 1,
      3, 5, and 10. RESULTS: The postoperative period was uneventful in all cases. Two
      hours after surgery, epithelial defects were found in all eyes and their length
      did not differ statistically p=0.47. On the first day after surgery, complete
      epithelization was observed in 30% of cases from Group I and 60% of cases from
      Group II. The average length of epithelial defects was reliably smaller in Group
      II than in Group I (p=0.04 respectively). On postoperative day 3, 20% eyes from
      Group I still had epithelial defects with the average length of 0.45+/-0.13 mm,
      while there was only one eye with a 0.2-mm epithelial defect in Group II.
      Finally, on postoperative day 5, there was a single 0.3-mm epithelial defect in
      one eye from Group I. On day 10, none of the patients had epithelial defects in
      either group. CONCLUSION: Epithelial wound healing at the site of corneal
      incision after non-complicated phacoemulsification was found to be faster in
      patients instilled with bromfenac twice daily than in patients receiving
      dexamethasone and diclofenac four times daily as anti-inflammatory therapy and
      given topical fluoroquinolones for antibacterial purpose.

PMID- 28745657
TI  - [Surgical treatment of rhegmatogenous retinal detachments with high risk of
      proliferative vitreoretinopathy].
AB  - AIM: to analyze the effect of internal limiting membrane (ILM) peeling in
      patients undergoing 23-gauge pars plana vitrectomy for the treatment of
      rhegmatogenous retinal detachment (RRD) with a high risk of proliferative
      vitreoretinopathy (PVR). MATERIAL AND METHODS: This was a prospective consecutive
      study of 231 eyes of 227 patients. All eyes underwent vitrectomy with silicone
      oil/gas tamponade for RRD with a high risk of PVR: in 42 eyes the ILM was peeled
      (group 1) and in the remaining 189 eyes - was not (group 2). The follow-up period
      was at least 3 months. RESULTS: In group 1, single-surgery anatomic success was
      achieved in 85.4% and definitive reattachment - in 95.2% of patients. In group 2,
      single-surgery anatomic success was achieved in 67.2% and definitive reattachment
      - in 89.4% of patients. None of the patients from group 1, who had their ILM
      peeled, developed epiretinal membrane. Final BCVA in groups 1 and 2 was 1.2+/-0.5
      logMAR and 1.34+/-0.82 logMAR respectively (p=0.297). CONCLUSION: ILM peeling
      during vitrectomy in RRD patients at high risk of PVR provides high primary
      anatomic success rate.

PMID- 28745658
TI  - [Results of corneal crosslinking for pellucid marginal corneal degeneration].
AB  - AIM: to evaluate the clinical effectiveness of crosslinking in patients with
      progressive pellucid marginal corneal degeneration (PMCD). MATERIAL AND METHODS:
      A total of 9 patients (16 eyes) with progressive PMCD were treated by standard
      crosslinking. The cornea was saturated with Dextralink solution and UV-A
      irradiated at 3 mW/cm2 for 30 minutes. The follow-up period was 12 months.
      RESULTS: One month after treatment, there was a slight decrease in uncorrected
      and best corrected visual acuity (UCVA and BCVA) - from 0.08+/-0.03 and 0.4+/
      0.15 preoperatively down to 0.06+/-0.02 and 0.3+/-0.07, respectively, caused by
      pseudohaze of the cornea. Keratometric parameters (the average refractive power
      of the cornea, corneal astigmatism, and corneal thickness) did not change
      significantly. The demarcation line was identified in 56% of cases. By the 3
      month follow-up, UCVA and BCVA improved up to 0.1+/-0.07 and 0.52+/-0.1,
      respectively. The refractive power of the cornea decreased by 2.0 diopters and
      corneal astigmatism - by 0.7 diopters reaching 46.8+/-2.7 and 5.1+/-1.3 diopters,
      respectively (p<=0.04). Central corneal thickness decreased by an average of 29
      microns. The demarcation line remained visible in 25% of cases. At 6 months, BCVA
      averaged 0.58+/-0.13, at that, 56% of eyes gained 1 line and 31% - 2 lines. The
      refractive power of the cornea decreased down to 45.7+/-1.6 diopters, corneal
      astigmatism - down to 4.8+/-1.5 diopters. The demarcation line was not detected.
      At 1 year, there were no significant changes in the average values of optometric
      indices as compared to the 6-month period. Sonclusion. Pellucid marginal corneal
      degeneration should be regarded as a kind of primary ectasia, often bilateral and
      notable for its characteristic clinical picture and late onset. In progressive
      disease, photochemical crosslinking of the cornea contributes to the improvement
      of optometric parameters and stabilization of the process.

PMID- 28745659
TI  - [Current approach and the role of laser photocoagulation in the treatment of
      retinal vein occlusions].
AB  - Despite the emergence of new approaches in the treatment of retinal vein
      thrombosis and post-thrombotic complications, namely, intravitreal
      pharmacotherapy and surgical treatment, laser photocoagulation continues to play
      a significant role in the management of patients with this pathology. Although
      the method of laser photocoagulation has been used for quite a long time,
      different views exist on its indications and execution in specific clinical
      situations. At that, not all opinions regarding the use of laser photocoagulation
      in thrombosis are based on convincing clinical studies. The aim of this work was
      to summarize current literature data on the use of laser photocoagulation in the
      integrated treatment of retinal vein occlusions and, also, to show which aspects
      of the treatment of thromboses can be considered well-established and reasonable
      and which remain a subject of debate.

PMID- 28745660
TI  - [Influence of vascular endothelial growth factor on angiogenesis and
      neurogenesis].
AB  - Vascular endothelial growth factor (VEGF) is known as a key mediator of
      angiogenesis, but there is also evidence of its broad significance in
      neurogenesis and neuroprotection. Cytokines of the VEGF family affect
      neovascularization and neural development in the brain, particularly during
      cerebral ischemia, in which there is a coordinated interaction of angiogenesis
      and neurogenesis that contributes to rapid functional recovery. This review
      examines the involvement of VEGF family members and their receptors in
      physiological and pathophysiological processes as well as the relationship
      between VEGF-A plasma levels and ischemic stroke.

PMID- 28745661
TI  - [n.s.i.n.i.V. Biomechanical aspects of anterior capsulotomy in cataract surgery].
AB  - This paper reviews studies on biomechanical properties of the anterior lens
      capsule. Early experiments in this field were more fundamental. Later studies
      were aimed mainly at assessing the mechanical stability of the capsule edge after
      manual or femtosecond laser capsulorhexis (capsulotomy) - an important step in
      modern minimally invasive phaco surgery. For biomechanical tests, ex vivo samples
      of human and animal anterior capsules were used. The results of the studies
      presented here are quite heterogeneous, which suggests the necessity of gaining
      further insight into the issue.

PMID- 28745662
TI  - [Atropine use for progressive myopia in children and adolescents].
AB  - The worldwide prevalence of myopia varies within the range of 20-50% among the
      adult population of Europe and the United States reaching 60-90% in Asian
      countries. Reduction of pediatric myopia rates is an important task of medicine.
      From many reported conservative methods for stabilization of myopia, those that
      involve pharmaceutical measures are worth paying attention to. This review covers
      publications dated 1964 or later that contain the results of atropine use at
      different concentrations in children and adolescents with a minimum follow-up
      period of 5 years. Atropine mechanisms of action and side effects at different
      concentrations of the drug are also analyzed. The authors point out potential
      health hazards for patients on atropine therapy. The principal conclusion: low
      dose atropine (0.01%) makes a good compromise between potential negative effects
      and statistically significant slowing of myopia progression proved in numerous
      studies. It is recommended that children at the age of 8-13 years undergo at
      least a 2-year course of atropine therapy.

PMID- 28745663
TI  - [Differential diagnosis of paroxysms of tonic muscle tension in children of early
      age with delay of psychomotor development and abnormal neurologic status].
AB  - AIM: To study neurologic status, results of video-EEG monitoring and magnetic
      resonance imaging in children under 3 years old with paroxysms of tonic muscle
      tension. MATERIAL AND METHODS: One hundred and forty-six infants and young
      children with motor disturbances and different variants of clinically similar
      epileptic seizures, hyperkinesis and stereotypes were examined. RESULTS AND
      CONCLUSION: Cerebral palsy (91%), genetic and chromosomal abnormalities (6%),
      brain malformations (2%) were identified. Neurological status was characterized
      by pseudobulbar syndrome (100% of cases), hemiparesis (1%), tetraparesis (81%),
      diffuse muscular hypotonia (18%), intellectual and speech development delay
      (76%), autistic behavior (16%). During the prolong video-EEG monitoring,
      paroxysmal tonic muscle tensions were recorded in all patients: epileptic
      seizures were observed in 113 patients (77.40%), non-epileptic paroxysms in 51
      (34.93%). The combination of epileptic and non-epileptic paroxysms was observed
      in 18 patients (12.33%). In 4 patients (2.75%), it was not possible to determine
      the genesis of paroxysms even during the prolong video-EEG-monitoring because of
      myographic artefacts. Five clinical and electroencephalographic combinations of
      dystonic attacks, epileptic seizures and epileptiform activity were identified.
      These data allow improving the diagnosis of epilepsy and avoiding unnecessary
      treatment with antiepileptic drugs. Our study has shown a high diagnostic value
      of video-EEG monitoring with the inclusion of sleep in patients with paroxysmal
      conditions in infancy and early childhood.

PMID- 28745664
TI  - [Predictors of cerebral complications during carotid endarterectomy].
AB  - AIM: To evaluate the prognostic value of parameters of cerebral oxygenation in
      estimation of the risk of ischemic stroke (IS) in perioperative and early
      postoperative phase of carotid endarterectomy (CEE). MATERIAL AND METHODS: Four
      hundred and sixty-six patients with hemodynamically significant atherosclerotic
      lesion of arteries of the brachiocephalic system, who underwent CEE with
      bilateral monitoring of cerebral oxygenation (rSO2), were enrolled. The end-point
      of the study was cerebral complications in perioperative and early postoperative
      phase. RESULTS: The perioperative level of rSO2 <50% (AUC 0.85 (0.73-0.96),
      p<0.05) and the reduction in rSO2 in the operated side during the temporary
      occlusion of the inner carotid artery (ICA) by >=20% (AUC 0.74 (0.51-0.97)
      p<0.05) were the best predictors of the risk of IS. The risk group with the
      reduction in rSO2 by >=20% at the main stage of CEE included patients with
      collateral stenosis and ICA occlusion, occlusion of the circle of Willis and the
      history of myocardial infarction. CONCLUSION: The reduction in rSO2 in the stage
      of ICA occlusion by >=20% increased the risk of IS by >10 times, the
      perioperative level of rSO2 <50% increased the risk of IS in perioperative and
      early postoperative phase of CEE by 6 times.

PMID- 28745665
TI  - [A role of clinical, psychological and social factors in the formation of hetero 
      and self-aggressive behavior of women serving time in a correctional facility].
AB  - AIM: To define a role of clinical, psychological and social factors in the
      development of aggressive behavior in women. MATERIAL AND METHODS: A total of
      1054 women serving their sentence in a penal colony were stratified into three
      groups: group 1 - 435 women with heteroaggressive behavior, group 2 - 298 women
      with self-aggressive behavior, group 3 (control group) - 321 woman without
      aggressive behavior. Clinical, psychological, sociological, and statistical
      methods were used. RESULTS AND CONCLUSION: The groups differed by the presence,
      severity and form of mental disorder and by psychological and social
      characteristics. It has been concluded that clinical and psychopathological
      factors play the most important role in the formation of aggression in women. The
      importance of psychological factors is ambiguous. They often play a secondary
      role but may be on parity or priority. The impact of social factors is often
      mediated.

PMID- 28745666
TI  - [Detection of effective treatment of amnestic mild cognitive impairement with
      cereton by testing of lipids markers].
AB  - AIM: Determination of effectivity and safety of Cereton (Choline alfoscerate,
      production by Sotex) 1200 mg/day in the treatment of cognitive functioning
      disorders in patients with amnestic mild cognitive impairment (aMCI) and
      determining its influence in the process (after a 3 month course of taking the
      drug) and 3 months after the end of treatment of aMCI on the change in the
      content of phosphatidylcholine, sphingomyelin, ceramide-metabolite sphingolipids
      and the activity of genes controlling the synthesis of enzymes, which control
      ithe metabolism of sphingomyelin and ceramide (sphingomyelinase and ceramidase).
      MATERIAL AND METHODS: The study involved a group of elderly patients (20 people),
      consisting of 14 women and 6 men, aged 51 to 82 years (mean age 70.3+/-9.1
      years). The patients' condition met the criteria for diagnosing aMCI syndrome.
      Analysis of phosphatidylcholine, sphingomyelin and ceramide in the blood plasma
      of patients was carried out by thin layer chromatography, expression of
      sphingomyelinase and ceramidase genes by RtPCR. RESULTS AND CONCLUSION: A sharp
      increase in the content of phosphatidylcholine and ceramide, the product of
      sphingomyelin hydrolysis, was detected. Expression of genes (acidic
      sphingomyelinase and ceramidase), controlling the metabolism of ceramide, is
      significantly reduced in the majority of patients in the treatment with ceretone.
      An increase in the level of phosphatidylcholine and a decrease in the expression
      level of the ceramide metabolism genes during treatment with ceretone and other
      drugs that affect the metabolism of phosphatidylchodine and sphingolipids can be
      used as markers of the effectiveness of therapy.

PMID- 28745667
TI  - [Prevention and correction of cognitive dysfunction after general anesthesia].
AB  - AIM: To evaluate clinical efficacy of intraoperative use of cytoflavin in the
      prevention and correction of cognitive functions in surgical patients with no
      history of neurological and psychosomatic disorders. MATERIAL AND METHODS: The
      study included 60 female patients who underwent surgery on the thyroid gland.
      Patients were stratified into two equal groups matched for main indices. Patients
      of the main group received infusions of cytoflavin (20 ml in 200 ml of 5% glucose
      solution). Patients underwent thyroidectomy with general inhalation anesthesia
      using desflurane. Cognitive testing was performed one day before operation and 6,
      24 and 48 h after. Waking time after stopping desflurane administration and time
      prior tracheal extubation were recorded. RESULTS AND CONCLUSION: The use of
      cytoflavin promoted the early post anesthesia adaptation and more rapid recovery
      of initial cognitive status of the patients.

PMID- 28745668
TI  - [An interim analysis of the results of treatment program implementation with the
      use of injectable extended-release naltrexone for opioid addicted patients].
AB  - AIM: To analyze outcomes of treatment in the 'Point of soberness' program for
      opioid addicted patients (2015-2016 gg.). MATERIAL AND METHODS: The results of
      treatment of 83 opioid addicted patients were analyzed. Seventy-four (89.16%)
      patients received treatment course of injections of extended-release naltrexone
      (from 4 to 6 injections), maintaining their participation in the outpatient
      medical rehabilitation program. Thirty-six (43.37%) patients completed a full
      course of injections of extended-release naltrexone. RESULTS AND CONCLUSION: The
      high efficacy of complex treatment with naltrexone injections was demonstrated.
      89% of patients achieved remission during the course of treatment.

PMID- 28745669
TI  - [Stenosis of the carotid artery in women with ischemic stroke and markers of
      inflammation].
AB  - AIM: To assess the relationship between the severity of stenosis of the carotid
      arteries, the level of female sex hormones and markers of subclinical
      inflammation in women with ischemic stroke (IS). MATERIAL AND METHODS: Two
      hundred and eleven women (mean age 68.9+/-9.23 years) were examined. A history of
      cardiovascular disease, previous cardiovascular events, type and subtype of
      stroke were recorded. Neurological status was assessed using neurological scales.
      Atherosclerosis was diagnosed by color duplex scanning of brachiocephalic
      arteries and laboratory testing (estradiol, markers of subclinical inflammation).
      RESULTS: Carotid artery stenosis of >=50% was found in 13.3% of patients, less
      severe stenosis in 36.0%. Stenosis of >=50% was positively correlated with the
      level of IL-18, TNF-alpha, and negatively correlated with the level of IL-6, IL
      4, and MMSE score. In dynamics, there was a decrease in the level of TNF-alpha in
      all groups of patients, and an increase in the IL-4 level in women with carotid
      artery stenosis of >=50%. CONCLUSION: Study of the influence of markers of
      subclinical inflammation on the atherosclerosis progression and recurrent
      disorders of cerebral circulation in women with IS should be continued.

PMID- 28745670
TI  - [The administration of neurocytoprotectors in a rat model of experimental spinal
      cord ischemia].
AB  - AIM: To study an effect of cortexin on functional recovery and morphology of the
      spinal cord of rats with spinal cord ischemia. MATERIAL AND METHODS: Spinal cord
      ischemia was achieved by ligation of the infrarenal abdominal aorta in 16 rats
      stratified into two equal groups: the ligation of infrarenal aorta was performed
      in the control group, aorta ligation was performed also in the experimental group
      with preliminary intraperitoneally administration of cortexin in a dose of 0.15
      mg/kg 30 min before procedure. Evaluation of neurologic deficit was performed by
      the Tarlov's scale. Morphological evaluation was made by analyzing the
      histological sections of the lumbar and sacral cord using the Nissl's method of
      coloring. Statistical analysis was performed as well. RESULTS AND CONCLUSION: A
      pronounced and significant effect of cortexin, which was clinically expressed in
      a decrease in neurological deficit (p=0.0095), morphologically in an increase in
      the number of normochromic neurons (r=0.01), and a decrease in shrunken neurons
      (r=0.0001) and shadow cells (r=0.0003), was noted. The results suggest a
      potential myeloprotective effect of cortexin. The drug can be considered in the
      context of treatment of vascular myelopathy.

PMID- 28745671
TI  - [A role of interactions between N-methyl-D-aspartate and dopamine receptors in
      facial emotion recognition impairment in schizophrenia].
AB  - AIM: To search for genetic mechanisms of facial emotion recognition (FER)
      impairment, one of the features of schizophrenia that affects social adaptation
      of patients. Based on the view implicating the interplay between dopaminergic and
      glutamatergic systems into the pathogenesis of schizophrenia, authors explored
      the interaction effects of the C366G polymorphism in the GRIN2B gene encoding
      NMDA receptor subunit NR2B with ANKK1/DRD2 Taq1A and 48-VNTR DRD4 polymorphisms
      on FER. MATERIAL AND METHODS: GRIN2B -DRD2 interaction effects were studied in a
      sample of 237 patients and 235 healthy controls, GRIN2B - DRD4 in 268 patients
      and 208 controls. RESULTS AND CONCLUSION: Both effects were significant in
      combined samples of patients and controls (GRIN2B X DRD2, F=4.12, p=0.043; GRIN2B
      X DRD4, F=6.43, p=0.012). Further analysis confirmed the interaction effect of
      GRIN2B and DRD2 polymorphisms on FER in patients with schizophrenia. In patients
      with a less efficient allele of the DRD2 in the absence of the minor allele of
      the GRIN2B C366G polymorphism, the results were close to normal values while
      patients with minor alleles of both polymorphisms showed the worst results. This
      finding is in line with the conceptions on a possible role of NMDA-receptor
      hypofunction and D2-mediated regulation of NMDA-receptor activity in FER
      impairments in schizophrenia.

PMID- 28745672
TI  - [Gender aspects of medico-social adaptation in adults with early onset of
      epilepsy].
AB  - AIM: To study the relationship between indicators of clinical picture and social
      adaptation in idiopathic and symptomatic epilepsies with onset before adulthood
      depending on patient's gender. MATERIAL AND METHODS: The cross-sectional study
      was carried out. The study group included 212 women and 171 men, aged 24-60
      years, with confirmed diagnosis of epilepsy with onset before 18 years. Seventy
      three patients were diagnosed with symptomatic epilepsy, 310 with idiopathic
      epilepsy. In 120 patients, the frequency of seizures was rarer than once a year.
      All patients had secondary education and were on treatment with antiepileptic
      drugs. RESULTS AND CONCLUSION: In symptomatic epilepsy with early onset, gender
      differences in family and educational status were not identified. Regardless of
      gender, patients with myoclonus had higher education more frequently than
      patients with absence and tonic-clonic seizures. Patients with the combination of
      different types of seizures, irrespective from etiology and gender, had secondary
      education more frequently. Women with rare generalized seizures more frequently
      had higher education and were married. Unmarried men with rare generalized
      seizures lived separately from their relatives more frequently. To author's
      opinion, the contradiction in indicators of social adaptation in men with rare
      generalized seizures, to the great extent, is related to the phenomenon of self
      stigmatization than to the influence of disease. The results can be used in
      rehabilitation of patients with idiopathic epilepsy syndromes.

PMID- 28745673
TI  - [Doctrine of psychopathy typology: E. Kretschmer's concept of 'key experience'
      and inherited defect].
AB  - The author analyzes the first concept of E. Kretschmer which preceded his famous
      concept of cycloid and schizoid temperaments: specific 'root' or 'key' experience
      characteristic of the personality type. This concept was built on the clinical
      data of patients with delusions but E. Kretschmer assumed that the difference in
      the degree of disease was not essential ('neurosis of reference' and 'sensitive
      delusion of reference' were more close than 'sensitive delusion of reference' and
      'expansive delusion'). For a sensitive psychopath, the key and specific
      experience is 'shameful defeat', for expansive psychopath - 'the violence over
      will by the common will'. Explanations of the phenomenon of psychopathic
      personalities made by E. Kraepelin and E. Kretschmer are compared as well as the
      relationship of psychopathic types determined by E. Kretschmer to 'the general
      psychopathic constitution'.

PMID- 28745674
TI  - [Gene mutations in patients with hereditary cavernous malformations].
AB  - AIM: To identify mutations in cerebral cavernous malformation (CCM) genes in
      patients with hereditary and sporadic CCMs in the Russian population. MATERIAL
      AND METHODS: Blood samples from 73 randomly selected patients, including 29 MRI
      confirmed familial cases, 8 clinically confirmed familial cases and 38 so-called
      sporadic cases, were examined. A search for large deletions/duplications was
      performed using multiplex ligation-dependent probe amplification (MPLA). For MLPA
      negative samples, the whole genome sequencing was performed to search for single
      nucleotide polymorphisms (SNP). RESULTS: Deletions in three genes (SSM1, SSM2,
      SSM3) were identified in 14 patients, including 5 without definitely established
      familial type, in whom the familial character of disease was not confirmed by
      clinical and neuroimaging results. SNP mutations were found in 13 patients, CCM
      gene mutations in 27. Mutations were detected in 91.7% of familial cases. In two
      patients, new CCM3 deletions were identified. Gene distribution was as follows:
      60.7 for CCM1, 32.2 for CCM2 and 7.1% for CCM3. In two members of a family with
      hereditary CCMs, no high effect mutations in the known CCM genes were found.
      Patients with mutations had greater severity of disease. Two patients with CCM3
      mutations demonstrated the most aggressive clinical course. De novo formation and
      growth of CCM were observed only in patients with mutations. CONCLUSION: The
      distribution of pathogenic mutations in known CCM genes is consistent with other
      large-scale studies. Familial CCMs are associated with more severe disease course
      and may be caused by mutations beyond the known CCM genes.

PMID- 28745675
TI  - [A rare case of rapidly progressing primary diffuse meningeal sarcomatosis of the
      brain and spinal cord].
AB  - Currently the differential diagnosis of anaplastic meningiomas often is quite
      complex. An interpretation of the data of radiological studies does not allow the
      exclusion of diseases with similar clinical course and character of a lesion,
      such as primary lymphoma and tuberculosis of the central nervous system,
      neurosarcoidosis and others. The article presents a clinical case, representing a
      rare and difficult to diagnose variant of anaplastic meningioma with extremely
      aggressive nature of the current and widespread involvement of the brain and
      spinal cord.

PMID- 28745676
TI  - [Anxiety in women undergoing surgical treatment of breast cancer].
AB  - AIM: To assess anxiety level and factors contributing to its development in
      patients undergoing surgical treatment for breast cancer. MATERIAL AND METHODS:
      The subjects of the study were 72 women, aged 20-80 years, with the diagnosis of
      primary breast cancer. The Basic Psycho-Oncological Documentation Scale (PO
      BADO), the European Organization for Research, and the Treatment of Cancer
      Quality of Life Questionnaire and its Breast Cancer Module (EORTC QLQ-C30; BR
      23), the Hospital Anxiety and Depression Scale (HADS) were used. RESULTS AND
      CONCLUSION: The anxiety score showed negative correlation with EORTC QLQ-C30
      'physical functioning', 'cognitive functioning', 'emotional functioning', 'global
      health status/quality of life' subscales (p<=0,002). Anxiety is a highly
      prevalent in women with breast cancer and has a marked negative impact, in
      particular on younger patients.

PMID- 28745677
TI  - [The agonist of dopamine receptors piribedil in treatment of Parkinson's
      disease].
AB  - In this paper, the authors review the current foreign and domestic literature on
      a role of the agonist of dopamine receptors piribedil in the treatment of
      Parkinson's disease. The results of the main studies of the efficacy and safety
      of piribedil, mechanisms of actions and a comparative characteristics with other
      dopamine receptors agonist are reviewed.

PMID- 28745678
TI  - [Functional (psychogenic) vertigo].
AB  - Psychogenic (functional) vertigo is in second place by frequency after benign
      positional paroxysmal vertigo. It is often difficult to make the diagnosis,
      diagnostic program is expensive and traditional treatment often is not effective.
      This literature review covers current concepts on the terminology, clinical
      signs, pathogenesis and treatment approaches with regard to functional vertigo.
      Special attention is given to cerebral mechanisms of the pathogenesis including
      cognitive aspects.

PMID- 28745679
TI  - [Low back pain and Modic changes].
AB  - Modic changes (MCh) are pathological changes in the bone marrow and the endplates
      of adjacent vertebrae characterized by bone marrow edema, fatty degeneration or
      osteosclerosis that are revealed by high-power field magnetic resonance imaging
      (MRI). The dominant disease pattern is a persistent back pain syndrome with
      varying intensity. It leads to difficulties in the interpretation of clinical
      data, evaluation of MRI data and treatment. The article presents a modern
      conception of the pathogenesis, classification, clinical implications and
      treatment of MCh based on national and foreign sources as well and the author's
      view on the osteogenic mechanism of the pathogenesis and treatment of MCh using
      intraosseous blockades.

PMID- 28745680
TI  - [The decreased level of plasma carnitine in patients with epilepsy].
AB  - Antiepileptic drugs (AEDs) have long been known to affect carnitine metabolism,
      dropping the plasma free carnitine. Valproate (VPA) was considered to be the
      strongest carnitine-reducing agent. VPA-induced hyperammonemic encephalopathy and
      hepatotoxicity are well known, and pre-existing carnitine deficiency can be a
      predisposing factor, especially in congenital metabolic disorders. Several
      studies have shown that carnitine supplementation in patients receiving VPA to
      result in subjective and objective improvements and to prevent VPA-induced
      hepatotoxicity and encephalopathy, in parallel with increases in carnitine serum
      concentrations. Level of free plasma carnitine <20 micromol/l (syn. carnitine
      deficiency) in patients with epilepsy (in 15-30% of cases) may occur not only
      with administration of VPA but with administration of other AEDs (phenobarbital,
      phenytoin, carbamazepine) and low nutritional intake of carnitine. Some findings
      indicate that the number of AEDs used is a risk factor for carnitine deficiency.
      It was established that body weight, height and multidrug therapy are
      significantly associated with low level of free plasma in epileptic patients.
      Carnitine deficiency can have severe consequences; but most epileptic patients
      suffering from it are asymptomatic. Although carnitine deficiency is not uncommon
      among patients receiving AEDs, it seems not necessary to routinely monitor
      carnitine levels in epileptic ambulatory patients, this is reasonable only in
      groups of risk. L-carnitine supplementation is clearly indicated in case of VPA
      induced hepatotoxicity (i.v. administration) VPA overdose (i.v. administration),
      primary carnitine-transporter defect and is strongly recommended in specific
      secondary carnitine deficiency syndromes, symptomatic VPA-associated
      hyperammonemia, infants and young children receiving VPA, especially those
      younger than 2 years, patients with a complex neurologic disorder, who are
      receiving multiple AEDs, patients who have risk factors for hepatotoxicity and
      carnitine insufficiency. In the absence of double blind trials, clinical practice
      is based on empiric observation, clinical experience, and theory. Well-designed
      studies of specific and general uses of L-carnitine replacement therapy in
      patients with epilepsy are needed.

PMID- 28745681
TI  - [Organization of out-patient psychiatric care in dementia and cognitive
      impairment. Part I: Memory clinics and Alzheimer's disease centers].
AB  - The review of publications on an influence of demographic changes in the
      population on the prevalence of old age dementias and a scale of burden of
      dementias in modern society are presented. This paper is the first part of the
      review. It presents the necessity of new forms of out-patient care to the aged
      with cognitive impairment. The author reviews the history of creation of memory
      clinics and Alzheimer's disease centers.

PMID- 28745682
TI  - [Risk factors and prevention of recurrent dynamics of depression].
AB  - The existing literature in the field demonstrates that in the majority of cases
      depressive disorder has a recurrent course that resulted in negative
      consequences: an increase in a number of chronic and marked episodes, a higher
      risk of suicide and stable cognitive deficit. An analysis of predictors promoting
      the formation of recurrent depressive disorder allows an identification of a
      constellation of biological, psychological, therapeutic, social factors which
      should be taken into account in the choice of methods of prevention of the next
      episode of depression. Currently, the prolonged supporting psychopharmacotherapy,
      including antidepressant therapy, is a main tactics in the prevention of
      recurrent dynamics of depressive disorder though its efficacy is understudied.

PMID- 28745683
TI  - [Genetic aspects of schizophrenia].
AB  - Schizophrenia is a disease with a complex non-Mendelian inheritance mechanism in
      most cases involving the combined action of a large number of genes. Identifying
      of genomic variations associated with schizophrenia endophenotypes has a great
      potential. This review describes genetic markers of the disease, current methods
      of their analysis, including genome-wide association study (GWAS). Certain genes
      with mutations that increase the risk of schizophrenia are described. Functional
      polymorphisms with phenotypic expression, which are significantly associated with
      clinical manifestation of schizophrenia, can serve as useful genetic markers. The
      authors highlight that currently there are no certain susceptibility genes.
      Further global research and search for markers in different population groups are
      needed.

PMID- 28745684
TI  - [Autoinflammatory diseases and kidney involvement].
AB  - Autoinflammatory disease (AID) is a new concept formulated from the results of
      studying the pathogenesis of familial periodic fevers, a heterogeneous group of
      genetically determined diseases characterized by causelessly recurrent
      exacerbations of the inflammatory process due to genetically determined disorders
      of innate immunity and accompanied by uncontrolled hypersecretion of interleukin
      1 (IL-1). These mechanisms were a basic model for understanding a wide range of
      rheumatologic and other inflammatory diseases of the internal organs. The late
      diagnosis of AIDs and their ineffective treatment increase the risk for the
      development and progression of secondary AA amyloidosis. Elaboration of both
      clinical and effective laboratory criteria for diagnosing autoinflammation is of
      great importance for determining the tactics of anti-inflammatory therapy and
      prevention of complications.

PMID- 28745685
TI  - [Membranous nephropathy in a Russian population].
AB  - AIM: To analyze the clinical and morphological manifestations of membranous
      nephropathy (MN) and to evaluate the efficiency of its therapy. MATERIAL AND
      METHODS: MN cases in 2009 to 2016 were retrospectively detected with a subsequent
      analysis of patients with primary MN (PMN). The titer of IgG-autoantibodies to
      phospholipase A2 receptor (anti-PLA2R Ab) was determined by an indirect
      immunofluorescence assay. Treatment outcomes, such as the time course of changes
      in proteinuria, nephrotic syndrome (NS), and the development of complete and
      partial remissions (CR and PR), were assessed. RESULTS: MN was detected in 201
      cases; the secondary etiology of the disease was established in 24.9%. The
      prevalence of MN among morphologically confirmed glomerulopathies was 14%; that
      of PMN was 10.4%. The median period to diagnosis PMN was 8 (5; 19) months. 150
      patients with PMN (66.7% were men; age was 50+/-15 years) were distributed
      according to the following morphological stages: Stages I (23.9%), II (48.5%),
      III (26.1%), and IV (1.5%). Elevated anti-PLA2R Ab levels were found in 51.6% of
      cases; NS in the presence of proteinuria was detected in 85.6% of patients. An
      estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 was seen in 25%
      of cases. Treatment outcomes were evaluated in 80 cases; the median follow-up
      period was 19 (8; 40) months. 68% of cases had CR (32%) or PR (36%) with a median
      follow-up of 26 (13; 44) months. Spontaneous CRs or PRs were observed in 7.5% of
      the patients. Multivariate analysis showed that the probability of CR or PR
      increased 3.2-fold in the use of cyclophosphamide and/or cyclosporine and
      decreased as eGFR dropped. CONCLUSION: In Russia, PMN is a common type of
      glomerulopathy, the specific features of which should include the low rates of
      spontaneous remissions and detection of anti-PLA2R Abs. For renal protection, the
      majority of patients with PMN require timely diagnosis and treatment;
      individualization of the choice of treatment and its enhanced efficiency call for
      further investigations.

PMID- 28745686
TI  - [Effects of keto/amino acids and a low-protein diet on the nutritional status of
      patients with Stages 3B-4 chronic kidney disease].
AB  - AIM: To evaluate the efficacy of keto/amino acids in maintaining protein balance
      and preventing mineral metabolic disturbances and the development of uremic
      hyperparathyroidism in the long-term use of a low-protein diet (LPD) in patients
      with Stages 3B-4 chronic kidney disease (CKD). SUBJECTS AND METHODS: Ninety
      patients with CKD caused by chronic latent glomerulonephritis in 65 patients and
      chronic tubulointerstitial nephritis of various etiologies (gout, drug-induced,
      and infection) in 25 were examined. The investigators conducted clinical,
      laboratory, and instrumental examinations, including bioelectrical impedance
      analysis (body mass index (BMI), the percentages of lean and fat mass),
      echocardiography and radiography of the abdominal aorta in the lateral projection
      (the presence of cardiac valvular and aortic calcification), and pulse wave
      velocity measurements using a Sphygmocor apparatus (vessel stiffness estimation).
      The stages of CKD were defined according to the 2012 Kidney Disease: Improving
      Global Outcomes (KDIGO) criteria; glomerular filtration rate was calculated using
      the CKD EPI equation. According to the diet used, all the patients were divided
      into 3 groups: 1) 30 patients who took LPD (0.6 g of protein per kg of body
      weight/day) in combination with the keto/amino acid ketosteril (1 tablet per 5 kg
      of body weight/day; Diet One); 2) 30 patients who used LPD in combination with
      the other keto/amino acid ketoaminol at the same dose (Diet Two); 3) 30 patients
      had LPD without using the keto/amino acids (Diet Three) (a control group).
      RESULTS: During a follow-up, there were no signs of malnutrition in Groups 1 and
      2 patients receiving LPD (0.6 g protein per kg/day) in combination with the
      keto/amino acids ketosteril and ketaminol, respectively. At the same time, 11
      (36.6%) patients in Group 3 (a control group) who did not take the keto/amino
      acids showed a BMI decrease from 24 (23; 26) kg/m2 to 18.5 (17; 19.2) kg/m2 (p <
      0.05), including that of lean body mass from 37.4 (36; 38.8) to 30 (29.1; 34.7)%
      in the men (p<0.05) and from 29.8 (26.8; 31) to 23.9 (22; 25.7)% in the women
      (p<0.01). In addition, at the end of the study, there were elevated serum
      phosphorus levels (p<0.05) and mainly higher parathyroid hormone concentrations
      in Group 3 patients who received LPD without using the amino/keto acids than in
      Groups 1 and 2. As compared to Group 3, Groups 1 and 2 displayed no differences
      in the quantity of cardiac and aortic calcification and in the augmentation index
      (arterial stiffness). The ketosteril and ketaminol groups versus the control
      group had also higher s-Klotho levels (p<0.01) that were inversely correlated
      with glomerular filtration rate (r =-0.467; p<0.01). CONCLUSION: The keto/amino
      acids ketosteril or ketoaminol are an important component of LPD, which prevents
      malnutrition and an additional source of calcium that inhibits hyperphosphatemia
      and slows the development of uremic hyperparathyroidism. Incorporation of
      keto/amino acids into LPD leads to a less pronounced reduction in s-Klotho
      protein in relation to the degree of renal failure than does LPD without
      keto/amino acids.

PMID- 28745687
TI  - [Nephrological aspects of complement-mediated thrombotic microangiopathy].
AB  - AIM: To analyze cases of complement-mediated thrombotic microangiopathy (C-TMA)
      in the daily practice of a hospital nephrology department, relative to the
      general aspects of the clinical course, therapy, and short-term outcomes.
      SUBJECTS AND METHODS: The prospective study conducted in the period June 1, 2015
      to June 1, 2016 included 10 patients with C-TMA newly diagnosed during
      hospitalization. Standard demographic parameters, generally accepted clinical
      data showing the severity of TMA and the involvement of vital organs were
      recorded at admission. Short-term outcomes of therapy (plasma therapy and/or
      eculizumab therapy), such as achievement of hematological remission and the need
      for maintenance therapy and renal replacement therapy (RRT), were evaluate.
      RESULTS: The median time from the onset of symptoms of the disease to diagnosis
      in the analyzed cases was 5 months (range 1 week to 26 months). The incidence of
      C-TMA among the inpatients of nephrology departments was 6.4 per 1,000 patients
      per year. Five patients were admitted to a clinic with symptoms of obvious
      extrarenal organ disorders; 4 of them had multiple organ dysfunction. Evident
      clinical symptoms of renal dysfunction were detected in all the patients, which
      necessitated RRT in 8 out of the 10 patients. Renal biopsy was performed in 7
      patients. All were found to have typical morphological manifestations of acute
      and chronic TMA. All the patients received plasma therapy; most of them had
      plasma exchanges; 4 patients took eculizumab. There were no fatal outcomes. All
      achieved hematological remission. Three of the 8 cases could achieve varying
      recovery of kidney function and stop dialysis. CONCLUSION: Analysis of this
      series of cases confirms the idea about the severity of TMA due to multiple organ
      dysfunction and the high risk of end-stage renal failure at late diagnosis. The
      key points of better renal prognosis are the earliest detection and treatment of
      the disease.

PMID- 28745688
TI  - [Risk factors for anemia in the early stages of chronic kidney disease].
AB  - AIM: To identify the early markers of anemia in chronic kidney disease (CKD) in
      patients with chronic glomerulonephritis (CGN) and glomerulonephritis (GN) in
      systemic diseases. SUBJECTS AND METHODS: Seventy-nine patients with some male
      preponderance who were aged 21 to 65 years (45.3+/-11.1 years) and had CKD (CGN
      and GN) in systemic diseases (systemic lupus erythematosus and Wegener's
      granulomatosis) in the early stages (Stages I-II) of CKD were examined. GN was
      diagnosed by a lifetime renal biopsy. Systemic diseases were diagnosed according
      to the criteria for each nosological entity. The stages of CKD were defined
      according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) criteria;
      the glomerular filtration rate (GFR) was calculated using the CKD EPI equation
      (2012). According to the presence or absence of anemia, all the patients included
      in the study were divided into 2 groups: 1) 43 (54.4%) anemic patients; 2) 36
      (45.6%) non-anemic patients (a control group). In addition to general clinical
      examination adopted for a nephrology department, special studies, such as
      determination of the serum levels of hepcidin, interferon-gamma (IFN-gamma),
      soluble Klotho protein (s-Klotho), as well as iron, ferritin, and transferrin
      saturation (TSAT) ratio, were performed to solve the set tasks. RESULTS: Forty
      three anemic patients who had a hemoglobin level of 110 (100; 119) g/l and 36
      control patients who had the similar values were noted to have statistically
      significantly (p<0.001) higher levels of IFN-gamma (11 (10; 14) and 0.2 (0.09;
      0.6) ng/ml), hepcidin (26 (25; 27) and 5.1 (3.8; 5.9) ng/ml) and C-reactive
      protein (1.5 (1.1; 2.1) and 0.3 (0.2; 0.6) mg/dl), and lower levels of s-Klotho
      protein (12 (10; 18) pg/ml) and TSAT (18 (14; 19)%. Forty-three patients with
      anemia were also found to have a statistically significantly (p<0.01) lower GFR
      (65 (62; 87) and 80.5 (62; 90) ml/min) and higher systolic blood pressure (145
      (125; 160) and 120 (115; 16) mm Hg) as compared with those in 36 control
      patients. At the same time, the compared groups displayed no statistically
      significant differences in serum ferritin levels (123 (110; 150) and 115 (100;
      140) ug/l). Among 43 CKD patients with anemia, its detection rate in the presence
      of systemic diseases was 3.2 times higher than that in CGN patients (41.7 and
      12.7%). ROC analysis revealed that in the CKD patients with CGN and GN, the serum
      hepcidin level >= 25 ng/ml, with the sensitivity and specificity being of 89.7%
      and 74%, respectively (p > 0.001), was associated with the development of anemia.
      Moreover, the hemoglobin level of<120 g/ l was found to have an independent
      impact on the risk of reducing serum s-Klotho production. CONCLUSION: In Stage I
      II CKD patients with CGN and GN in the presence of systemic diseases, elevated
      serum hepcidin levels should be regarded as a predictor for anemia of chronic
      disease (ACD). Herewith, the decrease in hemoglobin levels <120 g/l is associated
      with the reduced production of the nephroprotective factor s-Klotho. The
      treatment of ACD for Stages I-II CKD should encompass intravenous administration
      of iron in order to increase its content and availability for erythropoiesis.

PMID- 28745689
TI  - [Kidney injury molecules (KIM-1, MCP-1) and type IV collagen in the assessment of
      activity of antineutrophil cytoplasmic antibody-associated glomerulonephritis].
AB  - AIM: To assess the significance of determining the serum and urinary
      concentrations of monocyte chemotactic protein-1 (MCP-1), kidney injury molecule
      1 (KIM-1), and type IV collagen in patients with antineutrophil cytoplasmic
      antibody (ANCA)-associated vasculitis (AAV) to estimate the activity of renal
      involvement in AAV. SUBJECTS AND METHODS: 78 patients (32 men and 46 women)
      (median age 55 (45; 61) years) with AAV were examined. The patients were divided
      into 3 groups according to the AAV activity estimated using the Birmingham
      vasculitis activity Score (BVAS): 1) 25 patients with active ANCA-associated
      glomerulonephritis (GN); 2) 26 patients with active AAV without renal
      involvement; 3) 27 patients in sustained AAV remission. The serum and urinary
      concentrations of the markers were measured by enzyme immunoassay. RESULTS: The
      urinary concentration of all 3 biomarkers was higher in patients with renal
      involvement (Group 1); the differences in the levels of MCP-1 and type IV
      collagen were statistically significant as compared to Groups 2 and 3 (p<0.01),
      while that in KIM-1 level was only in Group 2. There were statistically
      significant correlations between the urinary concentration of these biomarkers
      and the traditional GN activity indices (erythrocyturia, daily proteinuria (DPU),
      total BVAS scores that reflect renal involvement, as well as serum creatinine
      levels and estimated glomerular filtration rate (p<0.05). ROC curve analysis
      showed that the urinary MCP-1 excretion of >=159 pg/ml had the highest (92%)
      sensitivity and urinary type IV collagen excretion of >=3.09 ug/l had the highest
      (86%) specificity in assessing the activity of ANCA-associated GN. At the same
      time, their diagnostic value increased in terms of a combination of DPU and ESR
      (96% sensitivity, 84.9% specificity). CONCLUSION: The urinary excretion of MCP-1,
      KIM-1, and type IV collagen reflects the severity of local renal inflammation in
      AAV patients and a study of these indicators is a promising diagnostic tool for
      assessing the activity of ANCA-associated GN.

PMID- 28745690
TI  - [Gender features of cardiovascular events in patients with chronic
      glomerulonephritis at the pre-dialysis stage of the disease].
AB  - AIM: To identify the gender differences of cardiovascular events in patients with
      chronic glomerulonephritis (CGN) at the pre-dialysis stage of chronic kidney
      disease (CKD). SUBJECTS AND METHODS: A total of 170 patients (median age 40+/-11
      years) with CGN who did not receive hemodialysis were examined. According to
      gender, all patients were divided into 2 groups: 1) 66 female patients with CGN;
      2) 104 male patients with CGN. All the patients underwent general clinical
      examination and transthoracic echocardiography. RESULTS: In the male group, body
      weight (70.2+/-12.3 vs 61.1+/-12.6 kg; p=0.000), daily proteinuria [2.286 (1.230
      3.541) vs. 1.421 (0.703-2.408) g; p=0.021], aortic diameter (3.43+/-0.36 vs
      3.15+/-0.32 cm; p=0.000), left atrial size (3.80+/-0.55 vs 3.52+/-0.49 cm;
      p=0.000), indexed left ventricular mass (LVM) (223.5+/-57.5 vs 205.5+/-54.6 g/m2,
      p=0.044) were significantly higher than those in the female group. Changes
      (atherocalcification) in the aortic valve structures were more common in the men
      than in the women (48% vs 22.7%; p=0.001), whereas the women were more frequently
      observed to have reverse blood flow along the right ventricle. CONCLUSION: In the
      men with CGN at the pre-dialysis stage of CKD, the increment in LVM index is
      associated with proteinuria and increases in right ventricle size, frequency of
      atherosclerotic changes in the aortic valve, and left atrial longitudinal size.

PMID- 28745691
TI  - [Causal relationships in stroke and kidney injury].
AB  - AIM: To assess the frequency, severity, and causes of acute kidney injury (AKI)
      in patients with stroke. SUBJECTS AND METHODS: 272 patients (143 men and 129
      women) (mean age, 66.7+/-11.6 years) with stroke were examined. The 2008 European
      Stroke Organization (ESO) guidelines were used to diagnose stroke, to determine
      indications for and contraindications to thrombolytic therapy, and to evaluate
      its efficiency. Hemorrhagic and ischemic strokes (HS and IS) were diagnosed in 52
      (19%) and 220 (81%) patients, respectively. AKI was diagnosed and classified
      according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO)
      guidelines. RESULTS: AKI was diagnosed in 89 (33%) patients: 19 (36.5%) with HS
      and 70 (31.8%) with IS. The relative risk of death in patients with AKI
      associated stroke was 2.6 (95% confidence interval (CI) 1.6-4.0). A poor outcome
      (the combined endpoint of death or Rankin scale scores of 4-5) was noted in 56
      (62.9%) patients with AKI and in 70 (38.2 %) without AKI (chi2=14.6; p=0.0002).
      The relative risk of a poor outcome in patients with AKI-associated with stroke
      was 1.64 (95% CI 1.3-2.0). Forty-five (50.6%) patients with stroke developed AKI
      in the prehospital period. CONCLUSION: AKI complicates stroke in every three
      patients and increases death rates. 50% of cases develop AKI in the prehospital
      period due to the common causes of stroke and AKI.

PMID- 28745692
TI  - [Changes in the complement system in membranoproliferative glomerulonephritis].
AB  - AIM: To compare the clinical manifestations membranoproliferative
      glomerulonephritis (MPGN) in its idiopathic variant, lupus nephritis (LN), and C3
      glomerulopathy (C3-GP), by comparing them with changes in the complement system.
      SUBJECTS AND METHODS: The clinic of nephrology followed up 42 patients with
      different types of MPGN in 2013 to 2015. The study included 35 patients divided
      into 3 groups: 1) 8 patients with C3-GP, 2) 13 with idiopathic MPGN; 3) 14 with
      Class IV LN. The investigators studied the blood and urine levels of components
      and markers for activation of the classical and alternative pathways (C3 and C4,
      S3a, C5a, CFH, CFB, and CFD) of the terminal complement complex (TCC). RESULTS:
      The detection rate of C3-GP was 19%. The patients with C3-GP were noted to have
      the lowest blood concentration of S3 and the highest urinary level of S3a, C5a,
      TCC, CFH, CFB, and CFD. C3 nephritic factor was detected in 2 patients from the
      C3-GP (dense deposit disease) group. CONCLUSION: Alternative complement pathway
      dysregulation caused by genetic or autoimmune factors plays a leading role in the
      pathogenesis of C3-GP.

PMID- 28745693
TI  - [Efficiency of different celecoxib regimens in patients with active axial
      spondyloarthritis: Results of the 4-week pilot open-label comparative single
      center study 'AIM'].
AB  - AIM: To compare the efficiency and safety of two celecoxib regimens in the short
      term treatment of patients with axial spondyloarthritis (axSpA). SUBJECTS AND
      METHODS: Examinations were made in 40 patients with axSpA (the 2009 ASAS
      criteria; age, 38.5+/-12.1 years; 29 (72.5%) men; axSpA duration, 6.67+/-5.8
      years; BASDAI >=4.0), who were randomly divided into two groups: 1) 20 patients
      who received celecoxib 400 mg/day for 30 days; 2) 20 patients who took celecoxib
      600 mg/day for 7 days, then the drug was continued at a dose of 200 mg/day for 1
      month. High-sensitivity C-reactive protein (CRP) was determined; back pain was
      assessed using a visual analog scale; ASDAS-CRP scores were calculated at
      baseline (day 0) and on days 8 and 30. RESULTS: On days 0, 8, and 30 of taking
      celecoxib 400 mg, the back pain scores were 6.0+/-3.01, 5.06+/-2.04, and 5.53+/
      2.35; CRP levels, 24.13+/-21.46; 27.3+/-29.3%, and 13.1+/-21.3 mg/l; erythrocyte
      sedimentation rate (ESR), 15.25+/-14.36, 11.85+/-13.6, and 9.5+/-6.34 mm/h,
      respectively (p>=0.05 for all differences in all indicators relative to the
      baseline values). ASDAS was 3.34+/-1.02 at baseline, 2.74+/-1.14 on day 8, and
      2.18+/-1.05 on day 30 (p=0.016 and p=0,000 for differences from the baseline
      values). In the patients using the dose de-escalation of celecoxib, the back pain
      scores were 4.95+/-1.6, 4.11+/-1.0, and 4.89+/-2.1 at baseline and on days 8 and
      30, respectively (p=0.38 and p=0.065 for the differences from the baseline
      values); the CRP levels were 15.3+/-12.5, 12.1+/-10.8, and 7.5+/-4.5 mg/l,
      respectively (p=0.3 and p=0.001); ESR, 13.35+/-7.2, 15.7+/-11.6, and 15.16+/-8.9
      mm/h (p>=0.05). At baseline and on days 8 and 30, ASDAS was 3.1+/-0.6, 2.22+/
      0.7, and 3.47+/-0.56, respectively (p=0.02 and p=0.000). No differences were
      found in the rate of adverse events. CONCLUSION: Different regimens using
      nonsteroidal anti-inflammatory drugs demonstrated their feasibility, efficiency,
      and safety in AxSpA patients with high disease activity. The continuous use of
      celecoxib showed a gradual decrease in clinical and laboratory activity. The de
      escalation dose of celecoxib achieved a permanent laboratory activity reduction
      and pain relief when using 600 mg celecoxib, and after reducing its dose to 200
      mg/day, there was a decrease in laboratory disease activity without substantially
      changing the patients' functional activity. The safety of the comparable regimens
      was comparable.

PMID- 28745694
TI  - [Difficulties in the differential diagnosis of kidney injury in a patient with
      infective endocarditis associated with antineutrophil cytoplasmic antibodies].
AB  - Infective endocarditis (IE) may be accompanied by the production of a broad
      spectrum of autoantibodies, including antineutrophil cytoplasmic antibodies
      (ANCA). ANCA detection creates difficulties in the differential diagnosis of IE,
      especially in relation to kidney injury, the determination of the mechanism of
      which is important for choosing a treatment policy and estimating a prognosis.
      The paper describes a clinical case of a 57-year-old man who was found to have
      higher proteinase-3 (PR-3) ANCA titers along with the symptoms of anemia,
      purpura, and kidney injury during his hospitalization; echocardiography revealed
      vegetation on the aortic valve. IE was diagnosed; 2-week antibiotic therapy was
      ineffective; there was progressive aortic insufficiency necessitating aortic
      valve replacement. In the postoperative period, there was progression of renal
      failure and higher PR-3 ANCA titers, which made it possible to regard kidney
      injury as a manifestation of ANCA-associated glomerulonephritis. Intensive
      immunosuppressive therapy with intravenous and oral prednisolone was initiated,
      which showed positive effects in reducing proteinuria, erythrocyturia, serum
      creatinine levels, and simultaneously PR-3 ANCA titers. The paper gives the data
      available in the literature on the frequency of an association of IE with ANCA,
      the clinical features, diagnostic criteria, and treatment approaches. It
      discusses the mechanisms of ANCA formation in patients with IE.

PMID- 28745695
TI  - [MicroRNAs in chronic glomerulonephritis: Promising biomarkers for diagnosis and
      prognosis estimation].
AB  - The review presents the results of recent experimental and clinical studies of
      the expression pattern of a number of miRNAs, a recently described new class of
      noncoding RNAS that are able to regulate the posttranscriptional expression of
      genes and thus to modulate several physiological and pathological processes in
      different morphological types of chronic glomerulonephritis. It considers the
      possibilities of using miRNAs as new biomarkers to diagnose the disease, to
      predict its course and a response to therapy.

PMID- 28745696
TI  - [Obesity-related glomerulopathy: Mechanisms of development, clinical course].
AB  - Obesity and overweight are recognized as epidemics of non-communicable diseases
      in the 21st century. The kidneys are a target organ for obesity, damage to which
      is considered to be an independent risk factor for the development of renal
      failure. Obesity-related glomerulopathy (OGP) is one of the types of renal injury
      in obesity, which is characterized by the development of proteinuria in patients
      with a body mass index (BMI) of >30 kg/m2 in the absence of other causes of
      kidney damage. The pathogenesis of OGP is multifactorial. It is associated with
      intrarenal hemodynamic disorders - the development of renal hyperfiltration, the
      damaging action of adipose tissue hormones (hyperleptinemia, activation of the
      renin-angiotensin-aldosterone system, decreased production of adiponectin); with
      ectopic lipid accumulation in the kidney. The morphological pattern of OGP is
      characterized by a low glomerular density (oligonephronia) that leads to
      glomerular and tubular hypertrophy; by the development of perihilar focal
      segmental glomerulosclerosis (FSGS), obvious podocyte damages, and the
      development of a fatty kidney. The clinical picture of OGP is characterized by
      the slow and gradual development of albuminuria, not exceeding Stage A3 (300-1999
      mg/day). Approximately one-third of patients develop partial nephrotic syndrome
      with massive proteinuria, but without edema and hypoproteinemia. Complete
      nephrotic syndrome is observed in not more than 6% of patients with OGP. In the
      course of the disease, 50% of patients develop hypertension and more than 80% do
      dyslipidemia. Stages IV-V chronic kidney disease may develop 20-30 years after
      the disease occurs.

PMID- 28745697
TI  - [Role of the mechanisms of replicative cellular senescence in structural and
      functional changes of the vascular wall in chronic kidney disease].
AB  - This review considers the mechanisms and risk factors for the development of
      replicative cellular senescence of the vascular wall in patients with CKD and
      discusses therapeutic approaches to slowing the accelerated vascular aging.

PMID- 28745698
TI  - [Telmisartan in the treatment of hypertensive patients].
AB  - The paper highlights the use of telmisartan, one of the currently available
      angiotensin receptor blockers, for the treatment of patients with hypertension,
      metabolic syndrome, and those at high cardiovascular risk. Telmisartan treatment
      allows blood pressure control, provides organ protection at different stages of
      the cardiovascular continuum, and reduces the risk of cardiovascular diseases and
      death. The additional properties and pleiotropic activity of the drug determines
      its wide range of applications in cardiology.

PMID- 28745699
TI  - [Sacral resection in surgical treatment of locally advanced primary and recurrent
      rectal and anal cancer: short-term outcomes].
AB  - AIM: To assess safety of rectum removal with distal sacral resection. MATERIAL
      AND METHODS: The short-term results of surgical treatment of primary and
      recurrent locally advanced rectal and anal cancer with sacral fixation have been
      analyzed. 32 patients underwent combined operations with sacral resection at the
      level of S2-S5. In 12 patients only one point of tumor fixation (F1) was
      revealed, 10 patients had two points of fixation (F2), three patients had three
      fixation points (F3) and in 7 cases the tumor was fixed to four points (F4) of
      fixation to different pelvic structures. RESULTS AND DISCUSSION: Mean
      intraoperative blood loss and surgery time was 551+/-81 ml and 320+/-20 min in
      cases of sacral fixation only that was significantly lower compared with F2 cases
      - 1278+/-551 ml and 433+/-45 min, F3 cases - 2200+/-600 ml and 620+/-88 min, F4
      cases - 2157+/-512.5 ml and 519+/-52,3 min, respectively (r<0.05). Complications
      requiring surgical intervention occurred in 9% patients (n=3). Among 23 patients
      with intact bladder and ureters urinary disorders occurred in 42% (n=10).
      Resection margin was negative along posterior surface of the specimen in all
      cases. CONCLUSION: Advanced surgery with distal sacral resection is advisable for
      radical removal of locally advanced and recurrent rectal and anal canal cancer
      fixed to the sacrum with negative resection margin. These operations are feasible
      in specialized centers and should be performed by specially trained oncological
      or colorectal surgeon.

PMID- 28745700
TI  - [Laparoscopic surgery for colon cancer].
AB  - AIM: To assess laparoscopic surgery in treatment of colon cancer patients.
      MATERIAL AND METHODS: The results of laparoscopic treatment of patients with
      colorectal cancer are presented in the article. It was estimated the influence of
      various clinical parameters including age, gender, comorbidities, tumor
      localization and stage and complications on laparoscopic management of these
      patients. CONCLUSION: It was revealed that efficiency of laparoscopic surgery in
      patients with colon cancer is affected by tumor stage and presence of
      complications.

PMID- 28745701
TI  - [Early reconstruction of brachiocephalic arteries as a prevention of recurrent
      ischemic stroke].
AB  - AIM: To assess an efficacy and safety of brachiocephalic arteries reconstruction
      at the acute stage of stroke. MATERIAL AND METHODS: Early reconstruction of
      brachiocephalic arteries was made in 7 patients (mean age 67+/-9 years). Mean
      terms of brachiocephalic arteries reconstruction after stroke were 4.6 days
      (range 2-7 days). Pre- and postoperative neurological state was assessed by NIHSS
      score (mean preoperative score was 3.9+/-2.7 in these 7 patients, range 0-7). All
      patients had ipsilateral cerebral ischemic lesions with stenosis/occlusion of
      brachiocephalic artery. Their mean dimension was 10 mm (range 4-32 mm). Internal
      carotid artery stenting was made in 2 patients, carotid endarterectomy - in 4
      patients, stenting of the 1st segment of left subclavian artery - in 1 patient.
      RESULTS: There were no deaths and recurrent postoperative ischemic strokes.
      Complications developed in 2 patients: postoperative hematoma and intraoperative
      transient ischemic attack during ICA stenting in 5 days after stroke. There was a
      positive course of neurological state after brachiocephalic arteries
      reconstruction: mean score of neurological deficit decreased by almost 2 times
      (from 3.9+/-2.7 to 2+/-1.7). CONCLUSION: Early surgical prevention (within 7 days
      after stroke) may be effective and safe in certain patients with ischemic stroke
      (neurological deficit by Rankin score <=3 and NIHSS <=7, ischemic focus dimension
      less than 4 cm). Brachiocephalic arteries reconstruction early after stroke
      improves neurological state postoperatively by reducing motor and sensitive
      disorders. However, at present time there are no clear indications for early
      revascularization depending on either neurological deficit severity and ischemic
      focus dimension. So, our data should be confirmed by large trials.

PMID- 28745702
TI  - [Differential approach for chest wall reconstruction for pectus excavatum in
      adults].
AB  - AIM: To perform the prospective non-randomized single-center trial of pectus
      excavatum correction in adults. MATERIAL AND METHODS: For the period March 2012 -
      March 2016 64 patients aged 18-44 years were treated. Median age was 23 years.
      Male/female ratio was 41/23. All patients were included into standard survey
      protocol: chest MDCT, MRI of thoracic spine, pulmonary function test,
      echocardiography. Quality of life and complications rate after the Nuss procedure
      (n=50, 78.1%, group 1) and radical thoracoplasty using nikelid-titanium bar
      (n=14, group 2) were evaluated. RESULTS: There was earlier recovery in the 1st
      group: 3 (2; 4) and 6 (5; 7) days after minimally invasive and radical
      thoracoplasty, respectively. Postoperative Dindo-Clavien I-IIIa complications
      developed in 46 (71.8%) patients. Most of them did not require additional
      procedures. CONCLUSION: Nuss procedure is safe method and can be performed with
      good results in adults.

PMID- 28745703
TI  - [Creative surgery for hiatal hernia].
AB  - AIM: To present an experience of surgical treatment of hiatal hernia. MATERIAL
      AND METHODS: An experience of more than thousand laparoscopic fundoplications in
      various modifications has been accumulated in the Clinic of Bashkir State Medical
      University for the period 2001-2016. RESULTS: An original device for
      intraoperative measurement of hiatal orifice is described. Hiatal orifice repair
      was indicated in case of its dimension over 3.5 cm. 310 patients underwent hiatal
      orifice repair including diaphragmocrurorrhaphy in 189 cases, hiatal orifice
      replacement by using of mesh implant in 121 cases. Simultaneous interventions
      were performed in 211 cases due to hiatal hernia combined with other abdominal
      diseases. CONCLUSION: Thus, selection of hiatal hernia patients for antireflux
      surgery should be clearly indicated according to clinical and instrumental data
      in the context of health care system reforming and widespread use of minimally
      invasive technologies. Laparoscopic operations for hiatal hernia are preferable
      and contribute to decrease of morbidity and improvement of outcomes.

PMID- 28745704
TI  - [The minimally invasive video-assisted parathyroidectomy for primary
      hyperparathyroidism].
AB  - AIM: To study feasibility, effectiveness and safety of minimally invasive video
      assisted parathyroidectomy in patients with primary hyperparathyroidism; to
      define the advantages and disadvantages of this technique compared with
      conventional open surgery. MATERIAL AND METHODS: The study includes the results
      of 33 minimally invasive video-assisted parathyroidectomies performed in patients
      with primary hyperparathyroidism. The control group included 36 patients who
      underwent conventional open surgery. RESULTS: There were significantly increased
      time of surgery in the main group (41.2+/-12.7 min vs. 28.4+/-10.9 min, p<0.05),
      decreased need for postoperative analgesia (1,2+/-0.3 vs. 1.9+/-0.5 days, p<0.05)
      and significantly longer postoperative scar (1.8+/-0.2 vs. 6.2+/-0.5 cm, p<0.01).
      Incidence of complications was similar in both groups (6.1% vs. 8.3%, p>0.05).
      CONCLUSION: Minimally invasive video-assisted parathyroidectomy for primary
      hyperparathyroidism is feasible, safe and effective intervention that improves
      early postoperative course and cosmetic outcomes.

PMID- 28745705
TI  - [The outcomes of lower extremities burn wounds management by using of controlled
      moist environment].
AB  - AIM: To the outcomes of lower extremities burn wounds management by using of
      controlled moist environment. MATERIAL AND METHODS: Burn wounds management by
      using of controlled moist environment in 23 patients is presented in the article.
      Physiological moist conditions on the surface of wounds were created with
      isotonic sodium chloride solution and sterile polyethylene diaphanous containers.
      Sontrol group included 12 patients who were treated with hydrocolloid patch.
      RESULTS: It was shown that burn wounds management with moist environment allows
      to use and improve this method further. This technique gives good analgesic
      effect within the first days after burn trauma, allows to implement permanent
      clinical monitoring of the wound and preserve functional activity of the limbs.

PMID- 28745706
TI  - [The combination of endoscopic techniques in the diagnosis and treatment of
      various forms of infertility in women].
AB  - AIM: To improve the methods of simultaneous laparoscopy and hysteroscopy for the
      diagnosis and treatment of various forms of secondary infertility. MATERIAL AND
      METHODS: 420 women with various forms of infertility were examined and treated at
      the Caspian Hospital (Institute of Obstetrics and Gynecology). Patients were
      divided into three groups: tubal-peritoneal infertility - 212 women, different
      forms of endometriosis - 113 patients, polycystic ovarian disease - 95 women. We
      proposed safer method of laparoscopic surgery. RESULTS: There were no injuries of
      internal organs and bleeding from the puncture site if Veress needle and the
      first 'blind' trocar were deployed according to proposed method. We consider that
      choice of operative hysteroscopy technique should be differentiated in case of
      benign gynecological diseases. Anesthesia-free operative hysteroscopy by S.
      Bettocchi may be performed if diagnostic hysteroscopy is tolerable. Simultaneous
      laparoscopy and hysteroscopy are safe for patients.

PMID- 28745707
TI  - [Treatment of purulent wounds with wound dressing on a foamy basis with
      Hydrofiber technology].
AB  - AIM: to evaluate the effectiveness of modern approaches to the treatment of
      purulent wounds with the use of foam-based wound coatings with the Hydrofiber
      technology in comparison with the traditional method of wounds. MATERIAL AND
      METHODS: An analysis of the results of treatment of 34 patients with purulent
      wounds of various etiologies was performed. Patients were divided into two
      groups: control and basic. In the main group, local treatment of wounds was
      carried out using a foam-based wound coating with Hydrofiber technology. In the
      control group, local treatment of wounds was carried out using traditional
      methods with the use of gauze bandages. RESULTS: With the use of foam-based wound
      coatings with Hydrofiber(r) technology, the inflammation process in the wound and
      surrounding tissues is more rapidly eliminated, the periods of purification and
      microbial decontamination in the purulent focus are reduced.

PMID- 28745708
TI  - [Post-intubation tracheal rupture during transcatheter aortic valve
      implantation].

PMID- 28745709
TI  - [Diverticular disease of small intestine complicated by perforation and advanced
      peritonitis].

PMID- 28745710
TI  - [Autoplasmotherapy in coloproctology].

PMID- 28745711
TI  - [Mesenteric venous thrombosis].

PMID- 28745712
TI  - [Reconstruction of posttraumatic and postoperative defects of lower jaw].

PMID- 28745713
TI  - [Retracted article].

PMID- 28745714
TI  - [Telemedicine consultations in surgery. Analysis of the results and future
      prospects].

PMID- 28745715
TI  - Computer-based video analysis identifies infants with absence of fidgety
      movements.
AB  - BackgroundAbsence of fidgety movements (FMs) at 3 months' corrected age is a
      strong predictor of cerebral palsy (CP) in high-risk infants. This study
      evaluates the association between computer-based video analysis and the temporal
      organization of FMs assessed with the General Movement Assessment
      (GMA).MethodsInfants were eligible for this prospective cohort study if referred
      to a high-risk follow-up program in a participating hospital. Video recordings
      taken at 10-15 weeks post term age were used for GMA and computer-based analysis.
      The variation of the spatial center of motion, derived from differences between
      subsequent video frames, was used for quantitative analysis.ResultsOf 241
      recordings from 150 infants, 48 (24.1%) were classified with absence of FMs or
      sporadic FMs using the GMA. The variation of the spatial center of motion (CSD)
      during a recording was significantly lower in infants with normal (0.320; 95%
      confidence interval (CI) 0.309, 0.330) vs. absence of or sporadic (0.380; 95% CI
      0.361, 0.398) FMs (P<0.001). A triage model with CSD thresholds chosen for
      sensitivity of 90% and specificity of 80% gave a 40% referral rate for
      GMA.ConclusionQuantitative video analysis during the FMs' period can be used to
      triage infants at high risk of CP to early intervention or observational GMA.

PMID- 28745716
TI  - The role of phenotypic plasticity on population differentiation.
AB  - Several evolutionary processes shape the genetic and phenotypic differentiation
      of populations. Among them, the joint effects of gene flow, selection and
      phenotypic plasticity are poorly known, especially when trying to understand how
      maladaptive plasticity affects population divergence. We extended a quantitative
      genetic model of Hendry et al. (2001) to describe these joint effects on
      phenotypic and additive genetic divergence between two populations, and their
      phenotypic and genetic differentiation (PST and QST). With individual-based
      simulations, we tested our model predictions and further modeled allelic
      differentiation at neutral (FST) and adaptive (FSTQ) loci. While adaptive
      phenotypic plasticity allows for large phenotypic divergence and differentiation
      despite high gene flow, maladaptive plasticity promotes genetic divergence and
      generates countergradient variation, under extensive migration with phenotypic
      differences sometimes opposed to genetic differences. Maladaptive plasticity can
      also promote adaptive phenotypic divergence by reducing the effective gene flow.
      Overall, plasticity decouples genetic from phenotypic differences between
      populations, and blurs the correlation between phenotypic divergence and local
      adaptation. By deriving models of population differentiation for three different
      life cycles, we further describe the effect of a species' ecology on evolution in
      structured populations.

PMID- 28745718
TI  - The phenotypic correlates and quantitative genetics of masculinization in the
      rodent, Octodon degus.
AB  - This corrects the article DOI: 10.1038/hdy.2017.20.

PMID- 28745717
TI  - Evolution and conservation of Characidium sex chromosomes.
AB  - Fish species exhibit substantial variation in the degree of genetic
      differentiation between sex chromosome pairs, and therefore offer the opportunity
      to study the full range of sex chromosome evolution. We used restriction-site
      associated DNA sequencing (RAD-seq) to study the sex chromosomes of Characidium
      gomesi, a species with conspicuous heteromorphic ZW/ZZ sex chromosomes. We
      screened 9863 single-nucleotide polymorphisms (SNPs), corresponding to ~1
      marker/100 kb distributed across the genome for sex-linked variation. With this
      data set, we identified 26 female-specific RAD loci, putatively located on the W
      chromosome, as well as 148 sex-associated SNPs showing significant
      differentiation (average FST=0.144) between males and females, and therefore in
      regions of more recent divergence between the Z and W chromosomes. In addition,
      we detected 25 RAD loci showing extreme heterozygote deficiency in females but
      which were in Hardy-Weinberg equilibrium in males, consistent with degeneration
      of the W chromosome and therefore female hemizygosity. We validated seven female
      specific and two sex-associated markers in a larger sample of C. gomesi, of which
      three localised to the W chromosome, thereby providing useful markers for sexing
      wild samples. Validated markers were evaluated in other populations and species
      of the genus Characidium, this exploration suggesting a rapid turnover of W
      specific repetitive elements. Together, our analyses point to a complex origin
      for the sex chromosome of C. gomesi and highlight the utility of RAD-seq for
      studying the composition and evolution of sex chromosomes systems in wild
      populations.

PMID- 28745719
TI  - VIP cortical conductors set the tone for chronic pain.

PMID- 28745720
TI  - Corrigendum: Circuit specificity in the inhibitory architecture of the VTA
      regulates cocaine-induced behavior.

PMID- 28745721
TI  - Helping EGFR inhibition to block cancer.

PMID- 28745722
TI  - Erratum: Persistently active neurons in human medial frontal and medial temporal
      lobe support working memory.

PMID- 28745723
TI  - Corrigendum: Astrocytes mediate neurovascular signaling to capillary pericytes
      but not to arterioles.

PMID- 28745724
TI  - Is the boss watching?

PMID- 28745725
TI  - Corrigendum: A rapidly acting glutamatergic ARC->PVH satiety circuit
      postsynaptically regulated by alpha-MSH.

PMID- 28745726
TI  - CREATEd viruses go global.

PMID- 28745727
TI  - Corrigendum: Dopamine transients are sufficient and necessary for acquisition of
      model-based associations.

PMID- 28745728
TI  - [Quality of life of people with Parkinson's disease in the context of
      professional work and physiotherapy].
AB  - BACKGROUND: Of many diseases and disorders of the nervous system Parkinson's
      disease (PD) deserves a particular attention for its specific effects having an
      impact on the ability to undertake different forms of professional and economic
      activities. Due to the constantly growing incidence rate and the lowering age of
      patients, PD is becoming more and more serious social problem. The aim of this
      study was to determine the effects of professional work and physiotherapy on the
      quality of live in people with Parkinson's disease. MATERIAL AND METHODS: The
      research was carried out on 109 people with diagnosed PD of stage II according to
      the Hoehn and Yahr classification. They were divided into professionally working
      and non-working subjects and those participating and not participating in
      physiotherapy programs. The Unified Parkinson's Disease Rating Scale (UPDRS), was
      used to estimate the patients' clinical status. The Parkinson's Disease
      Questionnaire (PDQ-39), the Quality of Life Short Form (SF-36) Questionnaire and
      the Parkinson's Disease Quality of Life Questionnaire (PDQL) were used to
      estimate the quality of life. RESULTS: In all groups statistically significant
      differences were observed in each of the used scale. The PDQ-39 (F = 5.278, p =
      0.04), SF physical component (F = 4.24, p = 0.005), SF mental component (F =
      3.45, p = 0.021), PDQL (F = 6.57, p = 0.003). The highest quality of life was
      noticed in people working professionally and participating in physiotherapy
      programs. CONCLUSIONS: Professional activity and participation in properly
      planned physiotherapy help reduce the symptoms and improve the quality of life of
      people with Parkinson's disease. The study showed that the quality of life of
      people with PD is determined by professional work and participation in the
      process of rehabilitation. Med Pr 2017;68(6):725-734.

PMID- 28745729
TI  - Highlights of Skin Disease Education Foundation's 41st Annual Hawaii Dermatology
      SeminarTM.
AB  - New therapies, recent pathophysiological findings, and updated guidelines
      combined to create compelling presentations at the Skin Disease Education
      Foundation's 41st Annual Hawaii Dermatology SeminarTM. This educational
      supplement summarizes the highlights of clinical sessions presented during this
      CME/CE conference. A growing understanding of the biology of psoriasis has
      facilitated the development of increasingly efficacious medications. Skin
      clearance used to be regarded as an impractical goal for psoriasis therapy. Now,
      some clinical trials of newer medications report more than half of participants
      attaining Psoriasis Area and Severity Index (PASI) scores of 90. Two leading
      investigators review the latest findings about the treatment of this condition.
      Recent evidence demonstrates that psoriasis and psoriatic arthritis share
      multiple pathological underpinnings. A T helper type 17 (Th17) lymphocyte-based
      pathogenesis, genes, and microbiome changes have been identified in both
      conditions. Many therapeutics used in psoriasis care are efficacious in psoriatic
      arthritis. An expert in psoriatic arthritis updates readers about this condition.
      Cutaneous fungal infections, including onychomycosis, pose diagnostic and
      treatment challenges. New topical therapies and an investigational oral agent
      offer expanded options for management. The American Academy of Dermatology has
      issued new guidelines for the treatment of acne. Appropriate antibiotic use is a
      prominent theme. The US Food and Drug Administration has issued a communication
      about the risk of unintentional injection of soft tissue fillers into facial
      blood vessels-including blindness. The lead author of a recent review about this
      topic discusses how to prevent this serious outcome. The volume of new
      information about pathophysiology, diagnosis, therapy, and safety challenges our
      ability to keep current while enabling us to improve patient care. We hope that
      the highlights of this seminar offer you information that can be applied to your
      busy practices.

PMID- 28745730
TI  - Catalytic enantioselective aza-Diels-Alder reactions of unactivated acyclic 1,3
      dienes with aryl-, alkenyl-, and alkyl-substituted imines.
AB  - A catalytic enantioselective aza-Diels-Alder reaction of unactivated acyclic
      dienes with aryl-, alkenyl-, and alkyl-substituted imines is described. With 5-10
      mol% loadings of a new Bronsted acid catalyst, the aza-Diels-Alder reaction of
      unactivated acyclic dienes proceeded to give the corresponding aza-Diels-Alder
      adducts in high yields (up to 98%) with excellent enantioselectivity (up to 98%
      ee). Preliminary DFT calculations suggest that the reaction proceeds through a
      chiral ion pair intermediate.

PMID- 28745731
TI  - Zinc-coordination and C-peptide complexation: a potential mechanism for the
      endogenous inhibition of IAPP aggregation.
AB  - Aggregation of the highly amyloidogenic IAPP is endogenously inhibited inside
      beta-cell granules at millimolar concentrations. Combining in vitro experiments
      and computer simulations, we demonstrated that the stabilization of IAPP upon the
      formation of zinc-coordinated ion molecular complex with C-peptide might be
      important for the endogenous inhibition of IAPP aggregation.

PMID- 28745732
TI  - An amorphous FeMoS4 nanorod array toward efficient hydrogen evolution
      electrocatalysis under neutral conditions.
AB  - It is highly attractive to develop efficient hydrogen-evolving electrocatalysts
      under neutral conditions. In this communication, we report an amorphous FeMoS4
      nanorod array on carbon cloth (FeMoS4 NRA/CC) prepared by hydrothermal treatment
      of an FeOOH nanorod array on carbon cloth (FeOOH NRA/CC) in (NH4)2MoS4 solution.
      As a 3D electrode for hydrogen evolution electrocatalysis, this FeMoS4 NRA/CC
      demonstrates superior catalytic activity and strong long-term electrochemical
      durability in 1.0 M phosphate buffered saline (pH: 7). It needs an overpotential
      of 204 mV to drive a geometrical current density of 10 mA cm-2, which is 450 mV
      less than that for FeOOH NRA/CC. Density functional theory calculations suggest
      that FeMoS4 has a more favourable hydrogen adsorption free energy than FeOOH.

PMID- 28745733
TI  - Neutrophil extracellular trap formation upon exposure of hydrophobic materials to
      human whole blood causes thrombogenic reactions.
AB  - Neutrophil extracellular trap (NET) formation, a reaction of the innate immune
      system to fight pathogens, was shown to be involved in thrombus formation. In the
      present study blood-contacting biomaterials with graded surface characteristics
      were investigated as a potential cause of NET formation on medical devices.
      Surface properties are known to govern protein adsorption, cell adhesion and
      ultimately the activation of several other host defense pathways - potentially
      also the formation of NETs. Model materials of defined hydrophilic or hydrophobic
      properties (glass, and thin films of poly(ethylene-alt-maleic anhydride), self
      assembled monolayers of methyl terminated alkanethiols, and Teflon AFTM) were
      incubated either with isolated human granulocytes after pre-adsorption with
      plasma proteins or with human whole blood. NET formation - detected as
      extracellular DNA, citrullinated histones, elastase and reactive oxygen species
      (ROS) - was observed on hydrophobic surfaces. Furthermore, NET formation on the
      hydrophobic surface Teflon AFTM resulted in elevated thrombin generation in
      hirudin-anticoagulated whole blood, but not in heparinized whole blood.
      Disintegration of surface-bound NETs by DNase treatment resulted in significantly
      lower pro-coagulant effects. Thus, NET formation can contribute to the
      thrombogenicity of clinically applied hydrophobic materials, suggesting NETosis
      as well as NET surface anchorage as new targets of anticoagulation strategies.

PMID- 28745734
TI  - Charged poly(N-isopropylacrylamide) nanogels for use as differential protein
      receptors in a turbidimetric sensor array.
AB  - Due to the high cost and environmental instability of antibodies, there is
      precedent for developing synthetic molecular recognition agents for use in
      diagnostic sensors. While these materials typically have lower specificity than
      antibodies, their cross-reactivity makes them excellent candidates for use in
      differential sensing routines. In the current work, we design a set of charge
      containing poly(N-isopropylacrylamide) (PNIPAM) nanogels for use as differential
      protein receptors in a turbidimetric sensor array. Specifically, NIPAM was
      copolymerized with methacrylic acid and modified via carbodiimide coupling to
      introduce sulfate, guanidinium, secondary amine, or primary amine groups.
      Modification of the ionizable groups in the network changed the physicochemical
      and protein binding properties of the nanogels. For high affinity protein-polymer
      interactions, turbidity of the nanogel solution increased, while for low affinity
      interactions minimal change in turbidity was observed. Thus, relative turbidity
      was used as input for multivariate analysis. Turbidimetric assays were performed
      in two buffers of different pH (i.e., 7.4 and 5.5), but comparable ionic
      strength, in order to improve differentiation. Using both buffers, it was
      possible to achieve 100% classification accuracy of eleven model protein
      biomarkers with as few as two of the nanogel receptors. Additionally, it was
      possible to detect changes in lysozyme concentration in a simulated tear fluid
      using the turbidimetric sensor array.

PMID- 28745735
TI  - Phosphorescent 2-, 3- and 4-coordinate cyclic (alkyl)(amino)carbene (CAAC) Cu(i)
      complexes.
AB  - The photophysical properties of several Cu(i) complexes coordinated with cyclic
      (alkyl)(amino)carbene (CAAC) ligands were examined. All the compounds were found
      to be phosphorescent, regardless of whether they are 2-, 3- or 4-coordinated.
      Aggregate and excimer emission were observed from 2-coordinate CAAC-CuCl
      derivatives in methylcyclohexane solution. Emission from the complex 4
      coordinated with a trispyrazolylborate ligand is red-shifted with respect to both
      the chloro-derivative and an analogous complex with an NHC ligand.

PMID- 28745736
TI  - Liquid-solid phase transition of physical hydrogels subject to an externally
      applied electro-chemo-mechanical coupled field with mobile ionic species.
AB  - In this study, a model was multiphysically developed for the simulation of the
      phase transition of physical hydrogels between liquid solution and solid gel
      states, subject to an electro-chemo-mechanically coupled field, with the effect
      of the mobile ionic species in the solution. The present model consists of the
      governing equations for the equilibrium of forces and the conservation of mass,
      Maxwell's equations, and an evolution equation for the interface. Based on the
      second law of thermodynamics, the constitutive equations are formulated from the
      energy viewpoint, including a novel formulation of free energy with the effect of
      crosslink density. The present model may be reduced to Suo's non-equilibrium
      thermodynamic theory if the interface is ignored when only a single phase exists.
      It may also be reduced to Dolbow's model for gel-gel phase transition when the
      electric field is ignored. Therefore, the present model becomes more generalized
      since it is able to represent both the bulk phase and the interface behaviors,
      and the mechanical field is simultaneously coupled with both the electric and
      chemical fields. In the first case study, the system at equilibrium state was
      numerically investigated for analysis of the influences of the electrical and
      chemical potentials as well as the mechanical pressure externally imposed on the
      boundary of the system domain. The second case study presents a spherically
      symmetrical solution-gel phase transition at non-equilibrium states, with the
      emphasis on the evolution of both the interface and electrochemical potentials.

PMID- 28745737
TI  - On the use of the Cu2+-iminodiacetic acid complex for double histidine based
      distance measurements by pulsed ESR.
AB  - Cu2+ based distance measurements using the double-histidine (dHis) motif by
      pulsed ESR present an attractive strategy to obtain precise, narrow distance
      distributions that can be easily related to protein backbone structure
      (Cunningham et al., Angew. Chem., Int. Ed., 2015, 54, 633). The Cu2+-ion is
      introduced as a complex with the iminodiacetic acid (IDA) chelating agent, which
      enhances binding selectivity to the two histidine residues that are site
      selectively placed on the protein through mutagenesis. However, initial results
      of this method produced weak dipolar modulations. To enhance applicability of the
      double histidine motif using IDA, we perform a systematic examination of the
      possible causes of these weak dipolar modulations. We examine the efficiency of
      the Cu2+-ion to form the Cu2+-IDA complex in solution. In addition, we analyze
      the selectivity of Cu2+-IDA binding to dHis sites at both alpha-helical and beta
      strand environments. Our results indicate that the dHis motif on the beta-sheet
      sites have high affinity towards Cu2+-IDA while the dHis sites on alpha-helices
      show poor affinity for the metal-ion complex. We are able to use our new findings
      to optimize conditions to maximize dHis loading while minimizing both free Cu2+
      and unbound Cu2+-IDA complex in solution, allowing us to double the sensitivity
      of the Double Electron-Electron Resonance (DEER) experiment. Finally, we
      illustrate how Cu2+-based CW-ESR and DEER can be combined to obtain information
      on populations of different Cu2+-complexes in solution.

PMID- 28745738
TI  - Edges of graphene and carbon nanotubes with high catalytic performance for the
      oxygen reduction reaction.
AB  - We invented a practical and simple wet-grinding method to break conventional
      graphene sheets and CNTs for the production of new graphene/CNTs with adequate
      edge density (about 25 000 atoms per graphene-fragment of about 1 MUm2 in size)
      and no detectable changes in intrinsic defects, extrinsic impurities, and even
      surface-area. Measurements using the standard cyclic voltammetry, rotating disk
      electrode and rotating ring-disk electrode techniques all confirm that such
      mildly fragmented graphene, as well as carbon-nanotubes treated similarly using
      this wet-grinding method, can facilitate the fast 4-electron oxygen reduction
      reaction (ORR) pathway. Our first-principles computational studies of the ORR on
      graphene, as well as the relevant known data in the literature, support an
      intriguing proposition that the ORR can be speeded up simply by increasing the
      edge-density of graphene. The adsorption of O2 involving both oxygen atoms, which
      causes O-O elongation, is best facilitated at the edge of graphene, facilitating
      a multi-step 4-electron ORR process.

PMID- 28745739
TI  - Self-assembly of colloidal molecules that respond to light and a magnetic field.
AB  - This communication reports a novel method to prepare Janus particles with light
      responsive arylazopyrazole (AAP) polymer caps, which can be reversibly cross
      linked to chain-like colloidal oligomers in the presence of cyclodextrin (CD)
      functionalized superparamagnetic nanoparticles. The resulting colloidal molecules
      are light-responsive and can be controlled by an external magnetic field.

PMID- 28745740
TI  - Tuning band gaps and optical absorption of BiOCl through doping and strain:
      insight form DFT calculations.
AB  - Bismuth oxyhalides (BiOX, X = Cl, Br, and I) are a new family of promising
      photocatalysts. BiOCl and BiOBr possess large band gaps and weak absorption in
      visible light regions, which limit their applications. Although the band gap of
      BiOI is suitable to absorb most of the visible light, its redox capability is
      very weak. In this work, the doping and strain effects on the electronic
      structures and optical properties of BiOCl are explored using first principle
      calculations. The results show that doping in BiOCl, especially co-doping of Sb
      and I atoms, can obviously decrease the band gaps along with enhancing the
      optical absorption coefficients of pristine BiOCl because of the
      electronegativity difference between Sb/I atoms and Bi/Cl atoms. Meanwhile the
      band gap of BiOCl can be tuned under strain. This work offers potential
      strategies to enhance BiOCl absorption coefficients in the visible light region
      and its photocatalyst activity.

PMID- 28745741
TI  - Materials space of solid-state electrolytes: unraveling chemical composition
      structure-ionic conductivity relationships in garnet-type metal oxides using
      cheminformatics virtual screening approaches.
AB  - The organic electrolytes of most current commercial rechargeable Li-ion batteries
      (LiBs) are flammable, toxic, and have limited electrochemical energy windows. All
      solid-state battery technology promises improved safety, cycling performance,
      electrochemical stability, and possibility of device miniaturization and enables
      a number of breakthrough technologies towards the development of new high power
      and energy density microbatteries for electronics with low processing cost, solid
      oxide fuel cells, electrochromic devices, etc. Currently, rational materials
      design is attracting significant attention, which has resulted in a strong demand
      for methodologies that can accelerate the design of materials with tailored
      properties; cheminformatics can be considered as an efficient tool in this
      respect. This study was focused on several aspects: (i) identification of the
      parameters responsible for high Li-ion conductivity in garnet structured oxides;
      (ii) development of quantitative models to elucidate composition-structure-Li
      ionic conductivity relationships, taking into account the experimental details of
      sample preparation; (iii) circumscription of the materials space of solid garnet
      type electrolytes, which is attractive for virtual screening. Several candidate
      compounds have been recommended for synthesis as potential solid state
      electrolyte materials.

PMID- 28745744
TI  - Spin dependent interactions catalyse the oxygen electrochemistry.
AB  - The technological interest of oxygen reduction and evolution reactions, ORR and
      OER, for the clean use and storage of energy has resulted in the discovery of
      multiple catalysts; and the physical and catalytic properties of the most active
      compositions are only comprehensible with the consideration of magnetic
      interactions. Spin dependent potentials via exchange interactions, spin-orbit
      coupling or through magneto-electric effects catalyse the oxygen
      electrochemistry. The best catalysts show metal sites with localized spins and
      electron delocalization; a correlation exists between the rate constant for
      charge transfer reactions and spin-dependent electron mobility. Since during the
      OER and ORR the number of unpaired electrons is not conserved, magnetic
      potentials in optimum catalysts act as selective gates to enhance the transport
      of local spin currents. Overall magnetic potentials can reduce the bonding
      properties of the, donor or acceptor, orbitals in the catalyst, and electrons
      more easily transfer over the conduction band. The influence of spin dependent
      forces is generally applicable to oxygen catalysis, and supplements the physical
      interactions relevant for inorganic or organic, electro or photo, artificial or
      natural processes.

PMID- 28745745
TI  - Metal-free intermolecular cyclopropanation between alkenes and iodonium ylides
      mediated by PhI(OAc)2.Bu4NI.
AB  - A rapid, mild and metal-free intermolecular cyclopropanation between iodonium
      ylides and alkene-containing substrates mediated by PhI(OAc)2.Bu4NI is reported.
      Iodonium ylides of cyclic and acyclic 1,3-dicarbonyls were reacted with a variety
      of mono-, di-, tri- and tetra-substituted alkenes of various structural types to
      give 29 cyclopropanes in up to 97% yield.

PMID- 28745749
TI  - Comparison of dairy desserts produced with a potentially probiotic mixed culture
      and dispersions obtained from Gracilaria birdiae and Gracilaria domingensis
      seaweeds used as thickening agents.
AB  - Dairy desserts have emerged as interesting options for the incorporation of
      probiotics, bioactive ingredients and alternative sources of thickeners. This
      shows an opportunity to investigate the use of Gracilaria seaweeds in the
      formulation of potentially probiotic dairy desserts. This study aimed to compare
      the effects of dispersions obtained from Gracilaria domingensis and Gracilaria
      birdiae used as thickening agents on texture properties of dairy desserts
      fermented with SAB 440-A, composed of the starter Streptococcus thermophilus and
      the potential probiotics Bifidobacterium animalis and Lactobacillus acidophilus,
      and also to study their physicochemical characteristics, microbial viability and
      sensory acceptability. No significant differences between desserts with G.
      birdiae or G. domingensis dispersions regarding total solids, ash and fat
      content, as well as pH, titratable acidity, the viability of the microorganisms
      of the mixed culture and sensory acceptability were verified (P > 0.05).
      Nonetheless, the dessert with G. domingensis dispersion showed higher dietary
      fibre content and significantly increased firmness than the one produced with G.
      birdiae (P < 0.05). Moreover, B. animalis was able to maintain higher
      populations, above 7 log cfu g-1 during 21 days of storage of desserts, in the
      presence of either G. birdiae or G. domingensis dispersions, despite the fact
      that L. acidophilus has shown low viability in the final products. Therefore, the
      G. domingensis dispersion is suitable to be used as a thickening agent to produce
      dairy desserts with enhanced firmness and good sensory acceptability, it being
      also advisable to use only B. animalis as a probiotic for this product.

PMID- 28745750
TI  - Asymmetric alkylation of remote C(sp3)-H bonds by combining proton-coupled
      electron transfer with chiral Lewis acid catalysis.
AB  - The catalytic asymmetric alkylation of the remote, unactivated delta-position of
      N-alkyl amides was enabled by the combination of visible-light-induced proton
      coupled electron transfer, 1,5-hydrogen atom transfer, and chiral Lewis acid
      catalysis in up to 82% yield and up to 97% ee.

PMID- 28745751
TI  - Structuring and calorie control of bakery products by templating batter with
      ultra melt-resistant food-grade hydrogel beads.
AB  - We report the use of a temperature insensitive, food-grade hydrogel to reduce the
      caloric density of pancakes that were prepared at temperatures much higher than
      the boiling point of water. This cheap, facile method utilises a mixed agar
      methylcellulose hydrogel, which was blended to produce a slurry of hydrogel
      microbeads. The pancake batter was mixed with a controlled volume percentage of
      slurry of hydrogel beads and cooked. From bomb calorimetry experiments, the
      composites were found to have a reduced caloric density that reflects the volume
      percentage of hydrogel beads mixed with the batter. Using this procedure, we were
      able to reduce the caloric density of pancakes by up to 23 +/- 3% when the volume
      percentage of hydrogel beads initially used was 25%. The method is not limited to
      pancakes and could potentially be applied to various other food products. The
      structure and morphology of the freeze-dried pancakes and pancake-hydrogel
      composites were investigated and pores of a similar size to the hydrogel beads
      were found, confirming that the gel beads maintained their structure during the
      cooking process. There is scope for further development of this method by the
      encapsulation of nutritionally beneficial or flavour enhancing ingredients within
      the hydrogel beads.

PMID- 28745752
TI  - Optical absorption and magnetic circular dichroism spectra of thiouracils: a
      quantum mechanical study in solution.
AB  - The excited electronic states of 2-thiouracil, 4-thiouracil and 2,4-dithiouracil,
      the analogues of uracil where the carbonyl oxygens are substituted by sulphur
      atoms, have been investigated by computing the magnetic circular dichroism (MCD)
      and one-photon absorption (OPA) spectra at the time-dependent density functional
      theory level. Special attention has been paid to solvent effects, included by a
      mixed discrete/continuum model, and to determining how our results depend on the
      adopted DFT functional (CAM-B3LYP and B3LYP). Whereas including solvent effects
      does not dramatically impact the MCD and OPA spectra, though improving the
      agreement with the experimental spectra, the performances of CAM-B3LYP and B3LYP
      are remarkably different. CAM-B3LYP captures well the effect of thionation on the
      uracil excited states and provides spectra in good agreement with the
      experiments, whereas B3LYP shows some deficiency in describing 2-TU and 2,4-DTU
      spectra, despite being more accurate than CAM-B3LYP for 4-TU.

PMID- 28745753
TI  - The long-range convergence of the energetic properties of the water monomer in
      bulk water at room temperature.
AB  - The Interacting Quantum Atoms (IQA) energy partitioning scheme has been applied
      to a set of liquid water largely spherical clusters (henceforth called spheres)
      of up to 9 A radius, with a maximum cluster size of 113 molecules. This
      constitutes half of the commonly used 216 molecules in a typical simulation box
      of a liquid water box, and to our knowledge is the largest analysis of this kind
      ever undertaken. As well as demonstrating the topological analysis of large
      systems, which has only recently become computationally feasible, important long
      range properties of liquid water are obtained. The full topological partitioning
      of each sphere into atomic basins is used to consider the long-range convergence
      of the energetic and multipolar properties of the water molecule at the centre of
      each sphere. It is found that the total molecular energy converges to its 9 A
      value after 7 A, which corresponds to approximately the first three solvation
      shells, while the molecular dipole and quadrupole moments approximately converge
      after 5.5 A, which corresponds to approximately the first two solvation shells.
      The effect of water molecule flexibility is also considered.

PMID- 28745754
TI  - A study on the progress of mutarotation above and below the Tg and the
      relationship between constant rates and structural relaxation times.
AB  - Comprehensive FTIR studies on the progress of mutarotation in d-fructose mixed
      with maltitol have been carried out over a wide range of temperatures, both above
      and below the glass transition temperature Tg. In addition to the analysis of
      single bands, we have developed a completely new approach considering the full
      spectral range to follow the overall progress of the reaction. We have found that
      at the calorimetric Tg, there is a clear change in the temperature dependence of
      constant rates. The activation barrier for mutarotation changes from around 59 kJ
      mol-1 (the supercooled state) to around 249 kJ mol-1 (the glassy state). This
      dramatic variation in the activation barrier is consistent with the change in the
      mechanism of this specific chemical conversion, as theoretically considered by
      Wlodarczyk et al. [Phys. Chem. Chem. Phys., 2014, 16, 4694-4698]. Alternatively,
      it can also be connected to the change in the viscosity of the sample.
      Additionally, we investigated the relationship between constant rates (k) of
      mutarotation, structural relaxation times (taualpha), and dc conductivity
      (sigmadc) above and below the glass transition temperature. It was found that
      there was a linear correlation between all these quantities; they scale with
      various exponents changing at Tg. Our results also indicate that a single
      activation barrier might not be sufficient to describe the mutarotation process.

PMID- 28745755
TI  - Molecular engineering of lanthanide ion chelating phospholipids generating
      assemblies with a switched magnetic susceptibility.
AB  - Lanthanide ion (Ln3+) chelating amphiphiles are powerful molecules for tailoring
      the magnetic response of polymolecular assemblies. Mixtures of 1,2-dimyristoyl-sn
      glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phospho
      ethanolamine-diethylene triaminepentaacetate (DMPE-DTPA) complexed to Ln3+
      deliver highly magnetically responsive bicelles. Their magnetic properties are
      readily tuned by changing the bicellar size or the magnetic susceptibility
      Deltachi of the bilayer lipids. The former technique is intrinsically bound to
      the region of the phase diagram guarantying the formation of bicelles. Methods
      aiming towards manipulating the Deltachi of the bilayer are comparatively more
      robust, flexible and lacking. Herein, we synthesized a new Ln3+ chelating
      phospholipid using glutamic acid as a backbone: DMPE-Glu-DTPA. The chelate
      polyhedron was specifically engineered to alter the Deltachi, whilst remaining
      geometrically similar to DMPE-DTPA. Planar asymmetric assemblies hundreds of
      nanometers in size were achieved presenting unprecedented magnetic alignments.
      The DMPE-Glu-DTPA/Ln3+ complex switched the Deltachi, achieving perpendicular
      alignment of assemblies containing Dy3+ and parallel alignment of those
      containing Tm3+. Moreover, samples with chelated Yb3+ were more alignable than
      the Tm3+ chelating counterparts. Such a possibility has never been demonstrated
      for planar Ln3+ chelating polymolecular assemblies. The physico-chemical
      properties of these novel assemblies were further studied by monitoring the
      alignment behavior at different temperatures and by including 16 mol% of
      cholesterol (Chol-OH) in the phospholipid bilayer. The DMPE-Glu-DTPA/Ln3+ complex
      and the resulting assemblies are promising candidates for applications in
      numerous fields including pharmaceutical technologies, structural
      characterization of membrane biomolecules by NMR spectroscopy, as contrasting
      agents for magnetic resonance imaging, and for the development of smart optical
      gels.

PMID- 28745756
TI  - Frontiers of water oxidation: the quest for true catalysts.
AB  - Development of efficient and economic water oxidation catalysts (WOCs) remains a
      crucial bottleneck on the way to artificial photosynthesis applications. Over the
      past few decades, WOC research has turned into a fascinating interdisciplinary
      field that ranges from bio-inspired molecular design over nanomaterials and thin
      films to solid materials tuning. Under the umbrella of WOC optimization, advanced
      in situ/operando analytical techniques are being developed as increasingly
      powerful tools to elucidate the controversial discussions about the molecular or
      nanoscale nature of many WOCs. More and more of these approaches also enable the
      monitoring of possible key intermediates as an essential prerequisite for
      proposing catalytic mechanisms. This review is organized in three main parts:
      first, recent highlights outline frontiers in WOC development, such as the
      benefits of connecting molecular WOCs with solids along with the introduction of
      molecular concepts into heterogeneous WOC research. Next, a brief overview of
      emerging in situ/operando approaches demonstrates new options for monitoring WOC
      transformations. Finally, selected monitoring studies over the entire WOC
      dimensionality spectrum illustrate interesting cases of catalytic border
      crossings as new input for WOC construction.

PMID- 28745757
TI  - Styryl dye formation promoted by catalytic centers of piperazine bound to a
      silica surface traced by single molecule fluorescence microscopy.
AB  - The styryl dye (E)-2-[3-[4-(diphenylamine) phenyl]-1-(p-tolyl)-allylidene]
      malononitrile (DFTAM) was prepared by Knoevenagel condensation using homogeneous
      and surface bound amino catalysts. The catalysis by surface bound piperazine
      allowed the study of the condensation reaction at a single molecule (SM) level
      using total internal fluorescence microscopy (TIRFM). The turnover rate of the
      surface catalyst is dependent on the presence of the byproduct water of the
      condensation reaction. The addition of zeolite particles as water traps improves
      the catalytic activity indicated by the highest number of emissive centers mapped
      with super resolved fluorescence imaging and longest intensity-time trajectories
      showing SM bursting events. This particular condensation reaction highlights the
      applicability of the method to study multi-step organic reactions in the
      condensed phase in which the product is a fluorescent species.

PMID- 28745758
TI  - Influence of permittivity and energetic disorder on the spatial charge carrier
      distribution and recombination in organic bulk-heterojunctions.
AB  - In bulk-heterojunction organic solar cells the low permittivity in combination
      with the spatial and energetic disorder of the organic materials lead to a
      complex behavior of charge carriers within the active layer. Charges originate
      from exciton splitting at the heterojunction interface and the successive
      interplay between mutual Coulomb interactions and transport through the
      disordered organic can lead to insufficient separation from the interface,
      increased interface densities with respect to the bulk regions and, hence, affect
      recombination. To further understand the mechanisms of recombination, insight
      into the explicit spatial distribution of charge carriers within the blend is
      crucial. We performed kinetic Monte Carlo simulations on a bulk-heterojunction
      organic solar cell to assess the effect of Coulomb interactions and energetic
      disorder on the three-dimensional spatial distribution of charge carriers and
      highlight the correlation with both geminate and non-geminate recombination. We
      show that for materials with low permittivity and large energetic disorder the
      charge distribution is strongly inhomogeneous with accumulation along the
      heterojunction interface. In such cases recombination is not limited by
      recombination partners finding each other but rather an interface controlled
      process where geminate recombination dominates over nongeminate recombination.

PMID- 28745759
TI  - Comparison of the catalytic activity for O2 reduction of Fe and Co MN4 adsorbed
      on graphite electrodes and on carbon nanotubes.
AB  - We have compared the electrocatalytic activity of several substituted and
      unsubstituted Co and Fe N4-macrocyclic complexes (MN4) for the electro-reduction
      of oxygen with the complexes directly adsorbed on the edge plane of pyrolytic
      graphite or adsorbed on carbon nanotubes (CNTs). In the presence of CNTs, one
      order of magnitude higher surface concentrations of MN4 catalysts per geometric
      area unit could be adsorbed leading to a lower overpotential for the oxygen
      electro-reduction and activities in the same order of magnitude as the
      commercially available Pt/C catalysts in basic pH. From Koutecky-Levich
      regression analysis, the total number of electrons transferred was approximately
      2 for all the Co complexes and 4 for all the Fe ones, both in the presence and in
      the absence of the carbon nanotubes. Furthermore, the Tafel slopes did not vary
      due to the presence of the CNTs and presented values in the range of -0.06 V
      decade-1 for the CoN4 compounds and in the range of -0.04 V decade-1 for FeN4.
      When plotting the log of kinetic current densities (i.e. log jk) at a constant
      potential for each complex divided by the surface concentration Gamma, and the
      number of electrons transferred n for the ORR for each catalyst, versus the
      difference between the redox potential of the metal active site of the Co(ii)/(i)
      or Fe(iii)/(ii) catalyst and the reversible potential of the reaction they
      promote, the catalytic activity increases when the formal potential of the
      complex becomes more positive and the data obtained with complexes adsorbed on
      graphite are in agreement with the data obtained when using CNTs indicating that
      the increase in jk when CNTs are present is only due to an increase in the number
      of active sites per geometric area of the electrode.

PMID- 28745760
TI  - Advances in spectroscopy and dynamics of small and medium sized molecules and
      clusters.
AB  - Investigations of the spectroscopy and dynamics of small- and medium-sized
      molecules and clusters represent a hot topic in atmospheric chemistry, biology,
      physics, atto- and femto-chemistry and astrophysics. Nowadays, outstanding
      developments, both theoretical and experimental, have been achieved. The most
      recent results of these achievements are reviewed here. These molecular systems
      are studied by means of high-resolution spectroscopic techniques in either the
      frequency or the time domains. However, they still represent complex molecular
      systems since they may undergo processes that are still not fully understood in
      sufficient details. Indeed, electronic and nuclear motions may lead to complex
      features that are observed experimentally. From a theoretical point of view,
      these features can only be interpreted if the quantum nature of the atomic nuclei
      is considered together with the possible couplings between nuclear and electronic
      degrees of freedom. New developments, from both theoretical and experimental
      sides, are needed for modeling and engineering applications of outstanding
      importance. Possible future research directions are discussed.

PMID- 28745761
TI  - Study of the simulated sunlight photolysis mechanism of ketoprofen: the role of
      superoxide anion radicals, transformation byproducts, and ecotoxicity assessment.
AB  - The aim of this study was to investigate the photolysis mechanism of ketoprofen
      (KET) under simulated sunlight. The results demonstrated that the photolysis of
      KET aligned well with pseudo first-order kinetics. Radical scavenging experiments
      and dissolved oxygen experiments revealed that the superoxide anion radical (O2-)
      played a primary role in the photolytic process in pure water. Bicarbonate
      slightly increased the photodegradation of KET through generating carbonate
      radicals, while DOM inhibited the photolysis via both attenuating light and
      competing radicals. Moreover, Zhujiang river water inhibited KET
      phototransformation. Potential KET degradation pathways were proposed based on
      the identification of products using LC/MS/MS and GC/MS techniques. The
      theoretical prediction of reaction sites was derived from Frontier Electron
      Densities (FEDs), which primarily involved the KET decarboxylation reaction. The
      ecotoxicity of the treated solutions was evaluated by employing Daphnia magna and
      V. fischeri as biological indicators. Ecotoxicity was also hypothetically
      predicted through the "ecological structure-activity relationship" (ECOSAR)
      program, which revealed that toxic products might be generated during the
      photolysis process.

PMID- 28745762
TI  - A smartphone readable colorimetric sensing platform for rapid multiple protein
      detection.
AB  - A simple, visible and smartphone readable strategy has been proposed for the
      sensitive detection and discrimination of multiple proteins. By employing five
      different concentrations of NaCl salt, AuNP exhibited different aggregation
      behavior for different proteins because of differential ion strength, leading to
      diverse color changes. The sensing system could not only discriminate twelve
      proteins at the concentration of 50 nM in aqueous solution, but it could also
      discriminate these proteins at 200 nM in the presence of human urine with an
      accuracy of 100%. More importantly, based on the theory of chromatics, we could
      directly read out the color value using a smartphone to distinguish twelve
      proteins, pure Lys and HSA at various concentrations, and the mixture of these
      two proteins in the presence of human urine with no confusion after a
      hierarchical clustering analysis (HCA). The inexpensive and convenient
      colorimetric sensor array using the ubiquitous smartphone for signal readout has
      great potential for the point-of-care diagnosis without additional devices.

PMID- 28745763
TI  - Cobalt Schiff-base complexes for electrocatalytic hydrogen generation.
AB  - Two cobalt(iii) complexes containing inexpensive Schiff-base ligands have been
      found to be active for proton reduction at low overpotentials. The dinitro and
      tetranitro derivatized Schiff-base complexes show catalytic activity at -0.96 V
      and -1.1 V vs. Fc+/Fc, respectively, resulting in overpotentials of 120 mV and
      280 mV. Foot-of-the-wave analysis is used to examine the kinetic properties of
      these complexes, yielding a theoretical TOFmax of up to 4100 s-1. Experimental
      TOFs of 7 s-1and 3 s-1 are observed. Catalytic Tafel plots are also presented in
      order to benchmark the relationship between turnover frequency and overpotential.

PMID- 28745764
TI  - Control of targeting ligand display by pH-responsive polymers on gold
      nanoparticles mediates selective entry into cancer cells.
AB  - Selective targeting of cells for intracellular delivery of therapeutics
      represents a major challenge for pharmaceutical intervention in disease. Here we
      show pH-triggered receptor-mediated endocytosis of nanoparticles via surface
      ligand exposure. Gold nanoparticles were decorated with two polymers: a 2 kDa PEG
      with a terminal folate targeting ligand, and a di-block copolymer including a pH
      responsive and a hydrophilic block. At the normal serum pH of 7.4, the pH
      responsive block (apparent pKa of 7.1) displayed a hydrophilic extended
      conformation, shielding the PEG-folate ligands, which inhibited cellular uptake
      of the nanoparticles. Under pH conditions resembling those of the extracellular
      matrix around solid tumours (pH 6.5), protonation of the pH-responsive polymer
      triggered a coil-to-globule polymer chain contraction, exposing folate residues
      on the PEG chains. In line with this, endocytosis of folate-decorated polymer
      coated gold nanoparticles in cancer cells overexpressing folate receptor was
      significantly increased at pH 6.5, compared with pH 7.4. Thus, the tumour acidic
      environment and high folate receptor expression were effectively exploited to
      activate cell binding and endocytosis of these nanoparticles. These data provide
      proof-of-concept for strategies enabling extracellular pH stimuli to selectively
      enhance cellular uptake of drug delivery vectors and their associated therapeutic
      cargo.

PMID- 28745765
TI  - Controlled synthesis of high quality scandium-based nanocrystals as promising
      recyclable catalysts for silylcyanation reaction.
AB  - High quality (monodisperse and well-defined) scandium based ternary fluoride
      nanocrystals of NaScF4 and KSc2F7 were successfully fabricated via a one-pot
      colloidal synthesis method. These nanocrystals can play the part of hard Lewis
      acid catalysts by providing Lewis acid sites on account of the unique electronic
      structure, i.e. the ability of polarizing double bonds by coordination. As a
      proof of concept application, NaScF4 and KSc2F7 nanocatalysts were used to
      catalyze the silylcyanation reaction at room temperature, which exhibited
      excellent catalytic activity with outstanding recyclability.

PMID- 28745766
TI  - AC electric field controlled non-Newtonian filament thinning and droplet
      formation on the microscale.
AB  - Monodispersity and fast generation are innate advantages of microfluidic
      droplets. Other than the normally adopted simple Newtonian fluids such as a
      water/oil emulsion system, fluids with complex rheology, namely, non-Newtonian
      fluids, which are being widely adopted in industries and bioengineering, have
      gained increasing research interest on the microscale. However, challenges occur
      in controlling the dynamic behavior due to their complex properties. In this
      sense, the AC electric field with merits of fast response and easiness in
      fulfilling "Lab on a chip" has attracted our attention. We design and fabricate
      flow-focusing microchannels with non-contact types of electrodes for the
      investigation. We firstly compare the formation of a non-Newtonian droplet with
      that of a Newtonian one under an AC electric field and discover that
      viscoelasticity contributes to the discrepancies significantly. Then we explore
      the effect of AC electric fields on the filament thinning and droplet formation
      dynamics of one non-Newtonian fluid which has a similar rheological behavior to
      bio samples, such as DNA or blood samples. We investigate the dynamics of the
      thinning process of the non-Newtonian filament under the influence of an AC
      electric field and implement a systematic exploration of the non-Newtonian
      droplet generation influenced by parameters such as the flow conditions (flow
      rate Q, capillary number Ca), fluid property (Weissenberg number Wi), applied
      voltage (U) and frequency (f) of the AC electric field. We present the
      dependencies of the flow condition and electric field on the non-Newtonian
      droplet formation dynamics, and conclude with an operating diagram, taking into
      consideration all the above-mentioned parameters. Results show that the electric
      field plays a critical role in controlling the thinning process of the filament
      and the size of the generated droplet. Furthermore, for the first time, we
      quantitatively measure the flow field of the non-Newtonian droplet formation
      under the influence of an AC electric field, assisted by a high-speed micro
      particle imaging velocimetry (MUPIV) system. The flow field distributions
      obtained using the correlation algorithm show that the electric field generated
      Maxwell stress deforms the interface, changes the flow recirculation pattern,
      stimulates the instability and hence reduces the size of the non-Newtonian
      droplet. Finally, we analyze the impact of Maxwell stress by means of the
      electric capillary number CaE. Our findings reveal the rich physics of non
      Newtonian fluids and widen the applications of electric field in non-Newtonian
      environments, which could be critical for bioengineering.

PMID- 28745767
TI  - Phosphorus dendrimers for nanomedicine.
AB  - From biomaterials to imaging, and from drug delivery to drugs by themselves,
      phosphorus-containing dendrimers offer a large palette of biological properties,
      depending essentially on their types of terminal functions. The most salient
      examples of phosphorus dendrimers used for the elaboration of bio-chips and of
      supports for cell cultures, for imaging biological events, and for carrying and
      delivering drugs or biomacromolecules are presented in this feature article.
      Several phosphorus dendrimers can be considered also as drugs per se (by
      themselves) in particular to fight against cancers, neurodegenerative diseases,
      and inflammation, both in vitro and in vivo. Toxicity assays are also reported.

PMID- 28745768
TI  - The SOS Chromotest applied for screening plant antigenotoxic agents against
      ultraviolet radiation.
AB  - In this work, we investigated the usefulness of the SOS Chromotest for screening
      plant antigenotoxic agents against ultraviolet radiation (UV). Fifty Colombian
      plant extracts obtained by supercritical fluid (CO2) extraction, twelve plant
      extract constituents (apigenin, carvacrol, beta-caryophyllene, 1,8-cineole,
      citral, p-cymene, geraniol, naringenin, pinocembrin, quercetin, squalene, and
      thymol) and five standard antioxidant and/or photoprotective agents (curcumin,
      epigallocatechin gallate, resveratrol, alpha-tocopherol, and Trolox(r)) were
      evaluated for their genotoxicity and antigenotoxicity against UV using the SOS
      Chromotest. None of the plant extracts, constituents or agents were genotoxic in
      the SOS Chromotest at tested concentrations. Based on the minimal extract
      concentration that significantly inhibited UV-genotoxicity (CIG), five plant
      extracts were antigenotoxic against UV as follows: Baccharis nitida (16 MUg mL-1)
      = Solanum crotonifolium (16 MUg mL-1) > Hyptis suaveolens (31 MUg mL-1) = Persea
      caerulea (31 MUg mL-1) > Lippia origanoides (62 MUg mL-1). Based on CIG values,
      the flavonoid compounds showed the highest antigenotoxic potential as follows:
      apigenin (7 MUM) > pinocembrin (15 MUM) > quercetin (26 MUM) > naringenin (38
      MUM) > epigallocatechin gallate (108 MUM) > resveratrol (642 MUM). UV
      genotoxicity inhibition with epigallocatechin gallate, naringenin and resveratrol
      was related to its capability for inhibiting protein synthesis. A correlation
      analysis between compound antigenotoxicity estimates and antioxidant activity
      evaluated by the oxygen radical absorbance capacity (ORAC) assay showed that
      these activities were not related. The usefulness of the SOS Chromotest for
      bioprospecting of plant antigenotoxic agents against UV was discussed.

PMID- 28745769
TI  - A non-empirical calculation of 2p core-electron excitation in compounds with 3d
      transition metal ions using ligand-field and density functional theory (LFDFT).
AB  - Methodological advents for the calculation of the multiplet energy levels arising
      from multiple-open-shell 2p53dn+1 electron configurations, with n = 0, 1, 2,...
      and 9, are presented. We use the Ligand-Field Density Functional Theory (LFDFT)
      program, which has been recently implemented in the Amsterdam Density Functional
      (ADF) program package. The methodology consists of calculating the electronic
      structure of a central metal ion together with its ligand coordination by means
      of the Density Functional Theory code. Besides, the core-hole effects are treated
      by incorporating many body effects and corrections via the configuration
      interaction algorithm within the active space of Kohn-Sham orbitals with dominant
      2p and 3d characters of the transition metal ions, using an effective ligand
      field Hamiltonian. The Slater-Condon integrals (F2(3d,3d), F4(3d,3d), G1(2p,3d),
      G3(2p,3d) and F2(2p,3d)), spin-orbit coupling constants (zeta2p and zeta3d) and
      parameters of the ligand-field potential (represented within the Wybourne
      formalism) are therefore determined giving rise to the multiplet structures of
      systems with 3dn and 2p53dn+1 configurations. The oscillator strengths of the
      electric-dipole allowed 3dn -> 2p53dn+1 transitions are also calculated allowing
      the theoretical simulation of the absorption spectra of the 2p core-electron
      excitation. This methodology is applied to transition metal ions in the series
      Sc2+, Ti2+,..., Ni2+ and Cu2+ but also to selective compounds, namely SrTiO3 and
      MnF2. The comparison with available experimental data is good. Therefore, a non
      empirical ligand-field treatment of the 2p53dn+1 configurations is established
      and available in the ADF program package illustrating the spectroscopic details
      of the 2p core-electron excitation that can be valuable in the further
      understanding and interpretation of the transition metal L2,3-edge X-ray
      absorption spectra.

PMID- 28745770
TI  - The influence of ionic strength on the characteristics of heat-induced soy
      protein aggregate nanoparticles and the freeze-thaw stability of the resultant
      Pickering emulsions.
AB  - The improvement of the freeze-thaw stability of emulsions by interfacial
      engineering has attracted increasing attention in recent years. The present work
      investigated the potential of using soy protein isolate (SPI) aggregate
      nanoparticles as the Pickering stabilizers to improve the freeze-thaw stability
      of the resultant emulsions. SPI nanoparticles with different particle sizes and
      surface properties were fabricated through heating the SPI solutions (at a
      constant protein concentration of 2%, w/v) at 95  degrees C for 15 min, by
      varying the ionic strength (I) in the range of 0-500 mM. The nanoparticles
      fabricated at I values of 100-500 mM exhibited larger particle sizes and higher
      surface hydrophobicity, but poorer emulsification efficiency than those at I =
      0.05 mM. The presence of NaCl during the nanoparticle fabrication resulted in the
      formation of a kind of gel-like emulsion with a high extent of droplet
      flocculation. The emulsion stabilized by SPI nanoparticles at I = 0.05 mM was
      highly susceptible to coalescence, flocculation and creaming upon freeze-thaw
      treatment, while those in the presence of NaCl exhibited excellent freeze-thaw
      stability. The much better freeze-thaw stability of the emulsions in the presence
      of NaCl (relative to that at I = 0.05 mM) was largely attributed to the gel-like
      network formation, rather than the salt itself. The results indicated that a kind
      of Pickering emulsion with excellent freeze-thaw stability, stabilized by heat
      induced SPI nanoparticles, could be fabricated by heating the SPI solutions at I
      values of 100-500 mM. The findings would be of great relevance for providing
      important information about the development of food grade Pickering emulsions
      stabilized by protein-based particles, with potential applications in frozen
      food, or functional food formulations.

PMID- 28745771
TI  - Activation of the P-H bond by a frustrated Lewis pair and its application in
      catalytic Z-selective hydrophosphonylation of terminal ynones.
AB  - The frustrated Lewis pair (FLP) comprised of B(C6F5)3 and 1,2,2,6,6
      pentamethylpiperidine (PMP) can efficiently catalyze Z-selective
      hydrophosphonylation of terminal ynones with a Z/E selectivity of up to 20 : 1.
      Mechanistic studies suggest that the trans arrangement of the phosphite
      nucleophilic attack and hydrogen bond formation on the alkyne moiety is
      responsible for the observed Z-selectivity.

PMID- 28745772
TI  - Molecular dynamics simulations reveal disruptive self-assembly in dynamic peptide
      libraries.
AB  - There is significant interest in the use of unmodified self-assembling peptides
      as building blocks for functional, supramolecular biomaterials. Recently, dynamic
      peptide libraries (DPLs) have been proposed to select self-assembling materials
      from dynamically exchanging mixtures of dipeptide inputs in the presence of a
      nonspecific protease enzyme, where peptide sequences are selected and amplified
      based on their self-assembling tendencies. It was shown that the results of the
      DPL of mixed sequences (e.g. starting from a mixture of dileucine, L2, and
      diphenylalanine, F2) did not give the same outcome as the separate L2 and F2
      libraries (which give rise to the formation of F6 and L6), implying that
      interactions between these sequences could disrupt the self-assembly. In this
      study, coarse grained molecular dynamics (CG-MD) simulations are used to
      understand the DPL results for F2, L2 and mixed libraries. CG-MD simulations
      demonstrate that interactions between precursors can cause the low formation
      yield of hexapeptides in the mixtures of dipeptides and show that this ability to
      disrupt is influenced by the concentration of the different species in the DPL.
      The disrupting self-assembly effect between the species in the DPL is an
      important effect to take into account in dynamic combinatorial chemistry as it
      affects the possible discovery of new materials. This work shows that combined
      computational and experimental screening can be used complementarily and in
      combination providing a powerful means to discover new supramolecular peptide
      nanostructures.

PMID- 28745773
TI  - Drug design based on pentaerythritol tetranitrate reductase: synthesis and
      antibacterial activity of Pogostone derivatives.
AB  - Our previous work showed that Pogostone exerts antibacterial effects by targeting
      pentaerythritol tetranitrate reductase (PETNR). In order to develop derivatives
      of Pogostone with potent antibacterial activity, we performed molecular docking
      studies of Pogostone with PETNR and analyzed structure-activity relationships,
      which guided the structure design and the subsequent facile organocatalytic
      synthesis of Pogostone derivatives under mild reaction conditions. Several of the
      synthesized compounds showed antibacterial activity in vitro, including one
      compound (3h) that was highly effective against methicillin-resistant
      Staphylococcus aureus. These results suggest that Pogostone derivatives bearing
      functional groups on the side chain may be good leads for antibacterial drug
      development.

PMID- 28745774
TI  - The role of KCl in FeCl3-KCl/Al2O3 catalysts with enhanced catalytic performance
      for ethane oxychlorination.
AB  - Among the vinyl chloride production processes, ethane oxychlorination is the most
      economical and environment-friendly process but constrained by the lack of high
      performance catalysts for industrial applications. In this work, FeCl3-KCl/Al2O3
      catalysts with different molar ratios of K/Fe were prepared by a co-impregnation
      method and applied to ethane oxychlorination. The FeCl3-KCl/Al2O3 catalyst with
      K/Fe = 2 exhibited enhanced catalytic performance with the highest conversion of
      C2H6 (99.1%) and the best selectivity to C2H3Cl (74%) under the optimal
      conditions of 400  degrees C, C2H6 : HCl : air = 1 : 3 : 5.5 (volume ratio) and
      GHSV = 4560 h-1. It was found that the enhanced catalytic performance could be
      attributed to the formation of KFeCl4 from KCl and FeCl3 and the change of the
      reaction process. Besides, KCl is in favor of weakening the interaction between
      the active species and support. The reduction activation energy of Fe(iii) ->
      Fe(ii) is efficiently reduced by KCl addition. The FeCl3-KCl/Al2O3 catalyst may
      be a potential catalyst for industry due to its simple composition and convenient
      preparation.

PMID- 28745775
TI  - A highly stable l-alanine-based mono(aquated) Mn(ii) complex as a T1-weighted MRI
      contrast agent.
AB  - The synthesized lithium (S)-6,6'-(1
      carboxyethylazanediyl)bis(methylene)dipicolinate (Li3cbda) is a new chiral,
      alanine-based ligand bearing two picolinate functionalities. The trianionic form
      of the ligand [(cbda)3-] constitutes a seven-coordinate, water-soluble,
      pentagonal bipyramidal Mn(ii) complex (1). The structural analysis reveals the
      presence of a water coordinating site in the complex. The complex is
      thermodynamically very stable, and the stability is not affected by the presence
      of physiological anions (HCO3-, PO43-, and F-). The pH of the medium exerts a
      small effect on the stability of the complex. The r1 relaxivity of 3.02 mM-1 s-1
      is exhibited by the complex at 1.41 T, pH ~7.4, and 25  degrees C. Phantom images
      obtained via a clinical MRI BRIVO MR355 system established concentration
      dependent signal enhancement by the complex. The cytotoxicity test confirmed
      complex 1 as a biocompatible potential T1-weighted MRI contrast agent.

PMID- 28745776
TI  - Aryepiglottic fold augmentation as treatment for late-onset dysphagia following
      surgical treatment of recurrent laryngeal neuropathy.
AB  - OBJECTIVE: Coughing and dysphagia have been described following prosthetic
      laryngoplasty (LP) with or without ventriculectomy/ventriculocordectomy (VE/VCE)
      for the treatment of recurrent laryngeal neuropathy. All previous case
      descriptions include patients with acute onset of clinical signs after surgery
      that persisted. The authors observed a late-onset of dysphagia and coughing
      months to years after LP +/- VE/VCE. The condition was always associated with an
      abnormality of the aryepiglottic fold (AEF). Treatment options for those patients
      are limited. We suggest augmentation of the AEF as treatment for affected horses.
      The goal of the study was two-fold: Firstly, to describe a new condition of late
      onset dysphagia in horses following LP +/- VE/VCE associated with an abnormal
      appearance of the AEF, and secondly, to offer a minimally invasive and successful
      treatment for those patients. MATERIAL AND METHODS: Six horses were presented
      because of dysphagia and coughing with an onset of months to years after LP +/-
      VE/VCE. Endoscopically, the AEF always appeared thinner and more flaccid to a
      varying degree. The food path was traceable along the AEF into the trachea using
      dyed molasses. An initial injection of hyaluronic acid (HA) into the AEF led to
      immediate improvement of the dysphagia. The procedure was performed in the
      standing sedated horse. The needle was placed through the cricothyroid ligament
      and the injection performed under endoscopic guidance. RESULTS: All horses
      tolerated the injection well. Injection of HA was successful only in the short
      term in all cases and repeated injections were needed for permanent resolution
      using either cross-linked HA, polyacrylamide hydrogel or platelet rich plasma.
      CONCLUSION AND CLINICAL RELEVANCE: Horses may develop dysphagia and coughing
      months to years after LP +/- VE/VCE as a late-onset complication. The condition
      seems to be associated with an abnormal appearance and function of the AEF.
      Successful treatment is possible by augmenting the AEF. However, careful patient
      selection is mandatory.

PMID- 28745777
TI  - Comparison of two cold compression therapy protocols after tibial plateau
      leveling osteotomy in dogs.
AB  - OBJECTIVE: To evaluate two different protocols of cold compression therapy (CCT)
      for pain management and functional recovery in dogs undergoing tibial plateau
      leveling osteotomy (TPLO). MATERIAL AND METHODS: A total of 27 adult dogs (n = 30
      stifles; staged bilateral procedures: n = 3) undergoing routine TPLO were
      randomly allocated to three groups (n = 10/group). Dogs of group I received CCT
      once before and immediately after surgery. In dogs of group II CCT was performed
      postoperatively four times at 6-hour intervals. Dogs of the control group did not
      receive CCT. Circumference of the stifle joint and the following pain-related
      parameters were measured by a single blinded observer before surgery and 1, 10
      and 42 days after surgery: stifle joint range of motion (ROM), subjective degree
      of lameness, and score of a modified Glasgow Pain Scale (GPS). RESULTS: Both CCT
      groups showed significantly greater ROM and lower GPS scores 24 hours after
      surgery compared to the control group. Ten days after surgery there was a
      significantly lower degree of lameness in both CCT groups compared to the control
      group. Fourty-two days after surgery a significantly greater ROM was observed in
      both CCT groups compared to the control group. Group II also showed a significant
      improvement in the degree of lameness and GPS. There were no significant
      differences in any of the parameters between the two CCT groups at any time
      point. CONCLUSION: CCT applied preoperatively and immediately postoperatively
      showed similar short- and long-term beneficial results compared to a previously
      established protocol of applying CCT four times postoperatively. This protocol
      may be more suitable for practical use. CLINICAL SIGNIFICANCE: The reported data
      can be used to establish the new protocol of CCT in a clinical surrounding and to
      support postoperative rehabilitation of the canine patient.

PMID- 28745778
TI  - Conversion of Provider EMR Training from Instructor-Led Training to eLearning at
      an Academic Medical Center.
AB  - This case study overviews the conversion of provider training of the electronic
      medical record (EMR) from an instructor-led training (ILT) program to eLearning
      at an Academic Medical Center (AMC). This conversion provided us with both a
      useful training tool and the opportunity to maximize efficiency within both our
      training and optimization team and organization. eLearning Development Principles
      were created and served as a guide to assist us with designing an eLearning
      curriculum using a five step process. The result was a new training approach that
      allowed learners to complete training at their own pace, and even test out of
      sections based on demonstrated competency. The information we have leads us to
      believe that a substantial return on our investment can be obtained from the
      conversion with positive impacts that have served as the foundation for the
      future of end user EMR training at our AMC.

PMID- 28745779
TI  - [Emissions from dairy industry and the influence of herd management].
AB  - The purpose of this paper is to identify specific emission-reduction
      opportunities in dairy herds arising from aspects of useful herd management with
      the potential to reduce emissions, which are within the scope of veterinary
      activities. In future, it might be one of a veterinarian's advisory capacities to
      deal with the aspect of climate and environmental protection in animal husbandry.
      The models involved are similar to those of the national agricultural emission
      inventory. They allow quantifying the impacts of improved animal health, extended
      productive lifespan and grazing of an entire dairy herd (cows, calves, heifers
      and bulls) on emissions from the herd itself, in addition to those originating
      from the entire production chain, including provision of primary energy, water,
      feed production and processing. Ammonia emissions are the main focus. The
      reductions achieved here are not huge, though noticeable. They do not create
      extra costs. As can be shown, improved animal health and welfare are also
      environmentally beneficial. The reduction of greenhouse gas and air pollutant
      (eutrophying and acidifying gases and particles) emissions is an acknowledged
      political goal. If Germany wants to achieve the emission ceilings it has agreed
      to, agriculture will have to contribute. Planning will have to precede action if
      agriculture is itself to keep control of the processes.

PMID- 28745780
TI  - The ambient pollen distribution in Beijing urban area and its relationship with
      consumption of outpatient anti-allergic prescriptions.
AB  - OBJECTIVE: The impact of pollen exposure on allergy medication is poorly
      characterized. We aim to study the main kind of ambient pollen in Beijing urban
      area and the correlation with outpatient anti-allergic prescriptions throughout
      one year in a tertiary hospital. MATERIALS AND METHODS: With a modified
      volumetric trap, ambient pollens were sampled from January to December 2015.
      Meanwhile, information on 15 anti-allergic medication prescriptions in outpatient
      pharmacy was obtained and analyzed by generalized linear model. RESULTS: The
      total quantity of pollens amounted to 76164 grains in 2015. Two peaks of pollen
      concentration were observed, which happened from March to April 2015, and from
      August to September 2015. Consumption of antihistamines, LATRA, nasal sprays, and
      SABA showed two peaks trend in accordance with pollen distribution (p<0.01).
      ICS+LABA showed no seasonal peak without a significant correlation with pollen
      counts (p>0.05). Medication peak was higher in autumn than spring (p<0.01).
      CONCLUSIONS: The ambient pollen distribution was in accordance with the anti
      allergic prescription amount with the two-peak season. The autumn medication peak
      was higher than spring peak, which clarified that outpatients were more sensitive
      to autumn pollen compared with spring pollen.

PMID- 28745781
TI  - A study on the expression of FGF-21 and NF-kappaB pathway in the tissues of
      atherosclerotic mice.
AB  - OBJECTIVE: To study the relationship between the expressions of fibroblast growth
      factor (FGF)-21 and NF-kappaB signal transduction pathway in the tissues of
      atherosclerotic mice. MATERIALS AND METHODS: A total of 40 apoE-/- male mice at 8
      weeks were selected and randomly divided into 4 groups. 10 mice in group A were
      normally fed with diet. 10 mice in group B were fed with high-fat diet. 10 mice
      in group C were fed with high-fat diet + pravastatin. 10 mice in group D were fed
      with high-fat diet + subcutaneous injection of exogenous recombinant FGF-21
      protein. Another 10 C57BL/6J mice at 8 weeks were normally fed with diet (group
      E). They were killed after 12 weeks to collect retinal venous blood. ELISA method
      was applied to detect the levels of serum FGF-21, NF-kappaB, monocyte chemo
      attractant protein (MCP-1), matrix metalloproteinase (MMP)-9 and TNF-alpha.
      Immunohistochemical staining and RT-PCR method were applied to detect the
      expression of FGF-21 in aortic arch and liver tissues. RT-PCR method and Western
      blot method were applied to detect the expression of NF-kappaB, MCP-1, MMP-9 and
      TNF-alpha in aortic arch and liver tissues. RESULTS: The levels of serum FGF-21,
      NF-kappaB, MCP-1, MMP-9 and TNF-alpha in group B were higher than those of group
      A and group E, and those of group C and group D were lower than those of group B
      (except FGF-21 in group D). The differences had statistical significance
      (p<0.05). The positive staining rates of FGF-21 in endothelial cells of aortic
      arch and liver tissues in group B were higher than those group A and group E, and
      those of group C and group D were lower than those of group B. The differences
      had statistical significance (p<0.05). The expression levels of FGF-21mRNA, NF
      kappaB, MCP-1, MMP-9, TNF-alphamRNA and protein in endothelial cells of aortic
      arch and liver tissues in group B were higher than those group A and group E, and
      those of group C and group D were lower than those of group B. The differences
      had statistical significance (p<0.05). CONCLUSIONS: FGF-21 may participate in the
      occurrence of atherosclerosis (AS), which is related to the activation of the NF
      kappaB pathway. Lipid-lowering therapy can inhibit the activation of FGF-21 and
      NF-kappaB. Exogenous FGF-21 can also lower the activation of NF-kappaB and
      interpose in atherosclerosis process.

PMID- 28745782
TI  - Effects of heparin catheter-sealing solution for implantable venous access ports
      on D-dimer levels in older cancer patients.
AB  - OBJECTIVE: To investigate the effects of different concentrations of heparin
      catheter-sealing solution for implantable venous access ports (VAPs) on D-dimers
      (D-D) in older cancer patients. PATIENTS AND METHODS: A total of 208 older cancer
      patients who received intravenous chemotherapy for the first time were randomly
      divided into four groups: the normal saline group, the low concentration heparin
      group (25 U/ml), the medium concentration heparin group (50 U/ml), and the high
      concentration heparin group (75 U/ml), with 52 patients in each group. VAPs were
      sealed by the positive pressure technique every day before and after perfusion,
      as well as at the end of a course of chemotherapy when the butterfly needle was
      removed. The patients were followed-up for three courses of chemotherapy, and
      comparisons of the clinical effects were conducted. RESULTS: Before treatment and
      at the end of follow-up, no significant differences among groups were found in
      platelet count, prothrombin time, thrombin time, or activated partial
      thromboplastin time (p>0.05). At the end of follow-up, the high concentration
      heparin group had reduced fibrinogen (FIB) and increased D-D compared with the
      other groups, and the differences were statistically significant (p<0.05). The
      other three groups showed no significant differences in FIB or D-D before
      treatment or at the end of follow-up (p>0.05). The high concentration heparin
      group had higher local bleeding rate, while the saline group had higher partial
      and complete prevalence of blockage compared with the other groups. The
      differences were statistically significant (p<0.05). CONCLUSIONS: 25-50 U/ml
      heparin catheter-sealing solution had little effect on blood circulation and
      coagulation. Additionally, it did not increase the risk of local bleeding or
      thrombotic blockage.

PMID- 28745783
TI  - Modified fixation of indwelling intravenous catheter in management of exudate.
AB  - OBJECTIVE: To analyze the clinical efficacy of modified fixation of the
      indwelling intravenous catheter in the management of exudate. PATIENTS AND
      METHODS: From January 2015 to January 2016, 110 patients who underwent surgery
      and management of exudate were enrolled in this study. They were divided into two
      groups using a random number table with 55 patients in each group. Routine
      intravenous catheter fixation was used in the treatment group and modified
      intravenous catheter fixation was used in the control group. General condition
      and complications between 2 groups were compared. RESULTS: Our results showed
      that the off-bed time and nursing frequency in the treatment group were
      significantly shorter and lower than the control group while the indwelling time
      in the treatment group was significantly longer than the control group. The
      prevalence of redness, rash, erosion, and drainage tube infection in the
      treatment group was significantly lower than the control group. CONCLUSIONS: We
      concluded that modified fixation of the indwelling intravenous catheter could
      effectively prolong indwelling time while reducing the significantly the off-bed
      time, nursing frequency and occurrence of post-operative complications. We
      suggest that this method is valuable in clinical applications.

PMID- 28745784
TI  - Clinical research of different analgesia methods on perianesthetic pain of
      patients with moderate and severe craniocerebral injury who have emergency
      operation.
AB  - OBJECTIVE: To compare the effects of two different analgesia methods on
      postoperative pain of patients with moderate and severe craniocerebral injury who
      had an emergency operation. PATIENTS AND METHODS: In this study, 64 patients who
      were treated in our hospital from January 2015 to January 2016 and diagnosed with
      acute craniocerebral injury, were consecutively selected. The patients were
      divided into the propofol total intravenous anesthesia group (the observation
      group) and the isoflurane intravenous-inhalation combined anesthesia group (the
      control group) randomly with 32 cases each. Mean arterial pressure (MAP), partial
      pressure of oxygen (SpO2), and heart rate (HR) were compared and analyzed before
      and after anesthesia. At the first, second, and third day after the operation,
      adopt visual analogue scale (VAS), and sedation-agitation scale (GCS) were used
      to evaluate sedative and analgesic effects of patients. RESULTS: After anesthesia
      had succeeded, HR, SpO2, and MAP of patients in these two groups decreased, but
      the decrease in the observation group was less than that in the control group.
      The differences had statistical differences (p<0.05). At the first, second, and
      third day after the operation, scores of VAS and GCS in the observation group
      were obviously lower than those in the control group, and the differences had
      statistical differences (p<0.05). The total effective rate of anesthesia in the
      observation group was higher than that in the control group, and the differences
      had statistical differences (p<0.05). CONCLUSIONS: For patients with moderate and
      severe craniocerebral injury who had an emergency operation, propofol total
      intravenous anesthesia is more stable and has a better postoperative pain
      comparing with isoflurane intravenous-inhalation combined anesthesia.

PMID- 28745785
TI  - Analysis on the relationship and mechanism of high blood pressure and vascular
      aging on the condition that the gender and age matches.
AB  - OBJECTIVE: The relationship between hypertension and the mechanism of the
      expression of T-lymphocyte Kv1.3 channels in vascular aging has been analyzed in
      this study based on the gender and age matches' principle. PATIENTS AND METHODS:
      Thirty patients have been consecutively chosen with vascular aging caused by
      hypertension (group A), while 30 cases of high blood pressure not merged with
      vascular aging (group B) were chosen, and 30 cases of healthy volunteers (group
      C), conforming to gender and age 1:1 and the closest matching principle, were
      studied. The aim of this study was to separate the peripheral blood mononuclear
      cells and give intervention of 0.2 nmol/L ANGII to CD4 + T-lymphocytes, and store
      them in the incubator 48 h. The difference of Kv1.3 channel current of CD4 + T
      lymphocyte, mRNA, angiotensin receptor (AT1R) protein mRNA, and IFN-gamma density
      has also been compared. RESULTS: The membrane capacitance, peak current, and
      current density of group A, are higher than those of the other two groups, and
      the differences have statistical significance (p<0.05). After adding ANGII
      intervention to group A, the expression levels of T-lymphocyte Kv1.3 potassium
      channels mRNA, AT1R mRNA, and IFN-gamma are significantly increased, so that the
      difference has statistical significance p<0.05, while the other two groups have
      no significant change (p>0.05). The levels of Kv1.3 potassium channels, AT1R
      mRNA, and IFN-gamma of group A before and after the intervention are
      significantly higher than those of the other two groups, and the differences are
      statistically significant (p<0.05). CONCLUSIONS: Vascular aging caused by
      hypertension may be linked to the increase of Kv1.3 potassium channel activity of
      T-lymphocyte, while ANGII can improve the high expression of Kv1.3 potassium
      channel and AT1R, to stimulate lymph cells to secrete IFN-gamma.

PMID- 28745786
TI  - Impacts of serum P-selectin on blood pressure control after PCI in patients with
      coronary heart disease complicated with hypertension.
AB  - OBJECTIVE: We analyzed the impact of potent anti-hypertension or anti-thrombotic
      therapy after PCI in patients with coronary heart disease complicated with
      hypertension, whilst to reflect the prognosis by testing P-selectin. PATIENTS AND
      METHODS: A total of 177 patients with coronary heart disease (CHD) complicated
      with hypertension was continuously enrolled in this study and randomly divided
      into traditional anti-hypertension group (group A: 130/80 mm Hg <= BP <= 140/90
      mm Hg; anti-hypertensive drugs: beta blockers and angiotensin converting enzyme
      inhibitor, n=84) and potent anti-hypertension group (group B: BP <130/80 mm Hg;
      dosage and frequency in group B > group A, n=93). This study was approved by the
      Ethics Committee of Shaoxing People's Hospital. Signed written informed consents
      were obtained from all participants before the study. Patients who need a stent
      placed (CAG shows narrowed vascular diameter >=75%) have to continuously be
      followed-up for one year. Standard anti-hypertension (fluctuation of BP <5 mm Hg
      measured for 3 successive days) was detected respectively at admission and
      inpatient. The blood pressure, low-density lipoprotein cholesterin (LDL-C), high
      sensitivity C-reactive protein (hs-CRP) and P-selectin levels were tested 1 month
      and 1 year after discharge; the time of adverse events (AEs) was also recorded.
      RESULTS: There were no statistical differences between the occurrence times of
      AEs between group A and B (p=0.946). The P-selectin [(83+/-21) vs. (69+/-16)
      MUg/L, p=0.038], systolic pressure [(134+/-8) vs. (119+/-13) mm Hg, p<0.001] and
      diastolic pressure [(85+/-6) vs. (70+/-5) mm Hg] in group A were higher (p=0.001)
      than those of group B. Compared with P-selectin >=50.00 MUg/L, the median
      survival time (>12 vs. 10 months, chi2=3.621, p=0.047) of P-selectin <50.00 MUg/L
      was longer. By comparing P-selectin in different SBP grading (<120 mm Hg, 120-130
      mm Hg, 130-140 mm Hg), the difference was statistically significant (chi2=12.912,
      p=0.002). CONCLUSIONS: Potent anti-hypertension may influence the occurrence time
      of AEs after PCI in patients with coronary heart disease complicated
      hypertension. P-selectin can be a sensitive indicator. SBP has an apparent "J
      curve effect" and an appropriate anti-hypertensive scope (120-130 mm Hg).

PMID- 28745787
TI  - Short-term and long-term effects of covered stent endovascular graft exclusion
      for the treatment of abdominal aortic aneurysm rupture.
AB  - OBJECTIVE: We studied short-term and long-term effects of covered stent
      endovascular graft exclusion for the treatment of abdominal aortic aneurysm
      rupture. PATIENTS AND METHODS: From January 2013 to January 2016, 88 patients
      with fractured abdominal aortic aneurysm were enrolled in this study. Patients
      were divided into the control group or the open abdomen group (n=52) and the
      observation group or the isolated group (n=36). Patients in the control group
      were treated with open abdominal aneurysm resection and artificial blood vessel
      transplant technique, while patients in the observation group were treated with
      percutaneous stent graft endovascular graft exclusion. The outcome of two methods
      was compared. RESULTS: Surgical success rate and the mortality rate after 24 h
      and 30 days in the observation group were not significantly different than those
      in the control group (p>0.05). Short-term total mortality and complication rate
      in the observation group were lower than those in the control group and the
      differences were statistically significant (p<0.05). Operative time and
      intraoperative blood loss in the observation group was significantly less than
      those in the control group and the differences were statistically significant
      (p<0.05). The comparison of follow-up survival rate, recurrence rate, and
      secondary surgery rate in two groups showed no statistically significant
      differences (p>0.05). CONCLUSIONS: Short-term effects of endovascular graft
      exclusion for the treatment of abdominal aortic aneurysm rupture was superior to
      laparotomy, while the long-term effect was similar.

PMID- 28745788
TI  - The application value of continuous nursing for home oxygen therapy of patients
      in the stable phase of chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To analyze the application value of continuous nursing in improving
      the effects of home oxygen therapy for patients in the stable phase of chronic
      obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Patients in the
      stable phase of COPD (n=106) were selected and divided into the control group and
      observation group based on parity digit of their admission number. There were 53
      cases in each group. The patients in the control group received COPD health
      education at discharge, while the observation group received continuous nursing.
      The effect of home oxygen therapy in both groups after 3 months was compared.
      RESULTS: The compliance in the observation group for home oxygen therapy was
      significantly higher than that in the control group. Blood gas analysis and
      various indicators of pulmonary function in the control group at follow-up visits
      were not changed compared with those before. In contrast, partial pressure of
      blood oxygen and blood oxygen saturation of the observation group were lower than
      those before discharge. With the increasing partial pressure of carbon dioxide in
      arterial blood, the indicators of pulmonary function became lower than before.
      Comparing the various indexes between both groups at follow-up visits, the
      differences were statistically significant (p<0.05). The self-care ability and
      quality of life scores of patients in the observation group were higher than
      those of the control group, and the differences were statistically significant
      (p<0.05). CONCLUSIONS: By establishing health records and network platforms,
      continuous nursing can provide continuous health education and supervision for
      patients with COPD, which can effectively improve oxygen therapy compliance, self
      care ability and quality of life. It has good application and promotional value.

PMID- 28745789
TI  - Culture conditions of human embryonic stem cells for differentiation into retinal
      vascular structure.
AB  - OBJECTIVE: This study sought to identify the suitable cell culture conditions for
      the in vitro-induced differentiation of human embryonic stem cells (hESCs) into
      retinal vascular tissue cell types. MATERIALS AND METHODS: To do this, we
      established four treatment groups. Group A was designed to culture hESCs in a
      three-dimensional system. The feeder cells and leukemia inhibitory factor (LIF)
      were removed in Group B. In group C, hESCs were cultured with a variety of pro
      angiogenic growth factors. In group D, hESCs were cultured with intact retinal
      support cells and extracellular matrix. On days 15 and 30, the expression of
      platelet endothelial cell adhesion molecule 1 (PECAM1), alpha-smooth muscle actin
      (alphaSMA), and macrophage marker F4/80 were detected by immunofluorescence
      staining. ELISA was used to detect the expression of stromal cell-derived factor
      1 (SDF-1). RESULTS: At both 15 and 30 day timepoints, the highest PECAM1,
      alphaSMA, and F4/80 positive rates and SDF-1 expression levels were observed in
      group D, followed by group C, group B, with group A presenting the lowest
      expression of these proteins (p<0.05). Also, group D showed obvious angiogenesis
      structures. CONCLUSIONS: Our study indicates that hESCs can differentiate into
      retinal vascular-like structures. The presence of intact retinal support cells, a
      variety of cytokines, and extracellular matrix components were essential to
      facilitate this differentiation.

PMID- 28745790
TI  - The diagnostic value of three detection techniques of ultrasound in the active
      stage of Crohn's disease.
AB  - OBJECTIVE: The widespread availability of Ultrasound machines and their
      relatively low cost and functionality make them an attractive tool to use during
      the treatment of ongoing Crohn's Disease (CD). This study aims at exploring the
      value of conventional, power Doppler and contrast-enhanced ultrasound during the
      active stages of CD. PATIENTS AND METHODS: 24 patients in the active stages of
      Crohn's disease were enrolled in the study. The full, medial and lateral
      intestinal wall thicknesses and the thickness ratio of medial to lateral
      intestinal wall of the segmental lesions were measured by conventional
      ultrasound. The diseased intestinal wall was also examined by power Doppler
      ultrasound to assign Limberg classification types: 3 cases were Limberg II, 9
      cases were Limberg III and 12 cases were Limberg IV type. Importantly, the full
      and medial thicknesses of the intestinal walls with different Limberg types were
      compared, and statistically significant differences were found (p<0.05). Finally,
      images of the diseased segments were taken by contrast-enhanced ultrasound, and
      the contrast agent bolus arrival, the inflow and the peak enhancement times were
      calculated in order to be able to distinguish intestinal wall thickness
      differences according to different Limberg types. RESULTS: Cases with Limberg
      types III and IV mostly showed total intestinal enhancement, while Limberg II
      type cases showed mostly medial intestinal enhancement. When comparing the inflow
      and peak times of contrast-enhanced ultrasound of patients with different Limberg
      types, the differences found were statistically significant (p<0.05).
      CONCLUSIONS: This study confirms incrassation of the intestinal wall being the
      main ultrasonic appearance of active CD. Both power and contrast-enhanced
      ultrasound are effective tools in the management of active CD: while power
      ultrasound can be used to carry out Limberg typing, contrast-enhanced ultrasound
      can analyze and diagnose incrassation segments of the intestinal wall with
      different disease stages.

PMID- 28745791
TI  - The correlation between cognitive impairment and ambulatory blood pressure in
      patients with cerebral small vessel disease.
AB  - OBJECTIVE: The present study was aimed to analyze the correlation between
      cognitive impairment and ambulatory blood pressure in patients with cerebral
      small vessel disease (CSVD). PATIENTS AND METHODS: 108 patients with CSVD
      received in our hospital were selected. Assessment of cognitive impairment was by
      the Montreal Cognitive Assessment (MoCA). 39 cases were established as the
      impairment group and 69 cases were established as the normal group. 24 h
      ambulatory blood pressure was monitored, and changes in ambulatory blood pressure
      parameters between the two groups were compared. Also, the correlation between
      blood pressure parameters and MoCA score were analyzed. RESULTS: Comparisons of
      ambulatory systolic blood pressure, ambulatory pulse pressure and the ratios of
      night blood pressure reduction of patients in both groups showed statistical
      differences (p < 0.05), while the changes in diastolic blood pressure showed no
      statistical differences (p > 0.05). The comparison of the blood pressure curves
      in both groups showed statistical differences (p < 0.05). The ambulatory systolic
      blood pressure, ambulatory pulse pressure and the ratio of night blood pressure
      reduction of patients with CSVD showed prominently negative correlations with
      MoCA score (p < 0.05). CONCLUSIONS: Cognitive impairment and the ambulatory blood
      pressure of patients with CSVD are intimately correlated. The rise of ambulatory
      systolic blood pressure, pulse pressure, and the decline of blood pressure may
      represent risk factors for cognitive impairment in patients with CSVD. Improving
      blood pressure management will reduce the incidence of cognitive impairment
      caused by CSVD.

PMID- 28745792
TI  - Correlation between expression of LRP16, Ki67 and EGFR and breast cancer clinical
      pathologic factors and prognosis.
AB  - OBJECTIVE: To investigate the expression of leukemia-related protein 16 (LRP16),
      proliferating cell nuclear antigen K-67 (Ki67) and epidermal growth factor
      receptor-1 (EGFR-1) in breast cancer tissue and to explore the correlation
      between the expression of those proteins and breast cancer clinical pathologic
      factors and prognosis. PATIENTS AND METHODS: The expressions of LRP16, Ki67 and
      EGFR in breast cancer tissues of 86 cases were detected by the
      immunohistochemical method and the correlations between the expression of LRP16,
      Ki67 and EGFR and clinical pathologic factors and prognosis were investigated.
      RESULTS: Positive expression rates of LRP16, Ki67 and EGFR in breast cancer
      tissue were 52.3%, 70.9% and 16.3%, respectively. There was no statistical
      difference in the expression of RP16, Ki67 and EGFR between different age groups
      (p>0.05). The expression of LRP16 was correlated with clinical stage,
      histological grade, tumor size and lymphatic metastasis (p<0.05); the expression
      of Ki67 was correlated with clinical stage, histological grade, tumor size and
      lymphatic metastasis (p<0.05); the expression of EGFR was correlated with
      histological grade (p<0.05). Comparison of postoperative local recurrence and
      metastasis time between LRP 16 positive group and negative group showed
      statistically significant difference (p<0.05); comparison of postoperative local
      recurrence and metastasis time between Ki67 positive group and negative group
      also showed statistically significant difference (p<0.05); comparison of
      postoperative local recurrence and metastasis time between EGFR positive group
      and negative group showed no statistically significant difference (p<0.05).
      CONCLUSIONS: Detection of expression levels of LPR16, Ki67 and EGFR in breast
      cancer tissue improves the understanding of biological behaviors of breast
      cancer, which in turn provide clinical guidance in diagnosis, treatment and
      prognosis assessment.

PMID- 28745793
TI  - Hypoxia associated biomarkers in lung cancer - an update.
AB  - The high incidence rates of lung cancer have resulted in multiple progressions in
      cancer research leading to the development of novel therapeutic strategies. The
      three main branches of cancer research where improvements are being made are
      surgery, chemotherapy, and radiotherapy. These research developments have
      significantly improved the survival rates of cancer patients as most of these
      therapeutic options target specific molecules involved in cancer progression and
      metastasis. Experimental research has successfully identified potentially
      important molecules responsible for cancer progression. Further, the above
      molecular markers of disease are clinically approved biomolecules of significant
      prognostic value. The above molecular biomolecules also helped in rapid
      identification of subgroups of patients who need immediate emergency treatment.
      Hypoxia is one of such conditions where the human system is deprived of an
      adequate oxygen supply and requires immediate treatment. Hypoxia markers have
      been proved to be beneficial in the timely management of cancer. The present
      review is focused on the latest updates in the area of hypoxia related to markers
      in the prognosis of lung cancer.

PMID- 28745794
TI  - Expression of miR-210 in senile COPD complicating primary lung cancer.
AB  - OBJECTIVE: To analyze the expression and clinical significance of miR-210 in
      patients with senile chronic obstructive pulmonary disease (COPD) complicating
      primary lung cancer. 30 cases of COPD PATIENTS AND METHODS: 30 cases of primary
      lung cancer and 30 cases of COPD complicating lung cancer were selected. MiR-210
      can function as the cancer suppressor gene in progress from COPD to primary lung
      cancer and may be used as an important auxiliary diagnosis index. Analysis of
      correlations between MiR-210 expression with clinical features such as age, sex,
      disease type, COPD disease classification, pathological pattern of neoplasia and
      TNM staging. RESULTS: The expression of miR-210 of COPD Group was significantly
      higher than the Lung Cancer Group. The level of COPD Complicating Lung Cancer was
      the lowest (p < 0.05). There was no remarkable difference among sex, age, smoking
      status, hypertension, diabetes mellitus and pathological type in each group (p >
      0.05). Expression of miR-210 was lower with the aggravation of COPD and an
      increase of TNM staging (p < 0.05). CONCLUSIONS: MiR-210 expression level in the
      diagnosis of COPD complicating lung cancer had the sensitivity of 76.8%,
      specificity of 72.3%, accuracy of 0.73, 95% CI of 0.63-0.85 and critical value of
      0.1825.

PMID- 28745795
TI  - Research on the mechanism of HP mediated PI3K/AKT/GSK3beta pathways in gastric
      cancer.
AB  - OBJECTIVE: This study aimed to investigate the mechanism of Helicobacter pylori
      (HP) mediated PI3K/AKT/GSK3beta signal pathways in the occurrence of gastric
      cancer. PATIENTS AND METHODS: For this purpose, a total of 90 patients were
      selected; 30 were suffering from gastric cancer and gastric ulcer (observation
      group I), 30 were suffering from pure gastric ulcer (observation group II) and 30
      were with chronic gastritis (control group), and the lesion tissues were
      extracted by using endoscopy. Then, rapid urease test, RT-PCR and Western blot
      tests were conducted to detect the positivity rate of HP infection, the
      expression levels of PI3K/AKT/GSK3beta mRNA and protein respectively. RESULTS:
      The results showed that the positivity rate of HP infection, expression level of
      the PI3K/AKT/GSK3beta mRNA and protein from the samples of the observation group
      I were significantly higher than other two groups (p-value <0.05). CONCLUSIONS:
      HP may mediate the PI3K/AKT/GSK3beta signal pathways in the occurrence of gastric
      cancer.

PMID- 28745796
TI  - Safety and efficacy evaluation of laparoscopy in colorectal cancer with liver
      metastasis.
AB  - OBJECTIVE: To study the safety and efficacy of simultaneous completion of
      colorectal cancer resection and liver metastasis resection by total laparoscopy.
      PATIENTS AND METHODS: In the observation group, 40 patients with colorectal
      cancer combined with liver metastasis (CRCLM) were selected to receive total
      laparoscopic surgery. At the same time, 40 cases were selected for laparoscopic
      resection of colorectal cancer and hepatic resection as control group. RESULTS:
      The outcomes of the two methods in the treatment of CRCLM were compared. The
      results showed that the difference in surgery time between the two groups was not
      statistically significant (p>0.05). The blood loss, drainage tube retention time
      and anal exhaust recovery time in the observation group were significantly less
      than those in control group (p<0.05). No significant difference in completion
      rate was found between the two groups (p>0.05); the prevalence rate of
      complications in the observation group was significantly lower than that in
      control group (p<0.05). No significant differences in the median survival period
      and the survival rate at 1 year, 2 years and 3 years after surgery were found
      between the two groups (p>0.05). CONCLUSIONS: The outcomes of total laparoscopy
      in the treatment of CRCLM are not inferior to open surgery.

PMID- 28745797
TI  - Expressions and significances of TTF-1 and PTEN in early endometrial cancer.
AB  - OBJECTIVE: To analyze the expressions and significances of TTF-1 (Thyroid
      transcription factor-1) and PTEN (Phosphatase and tensin homolog) in early
      endometrial cancer. PATIENTS AND METHODS: 41 patients with endometrial cancer, 38
      patients with proliferative endometrium and 13 patients with normal endometrium,
      were selected. The fluorescence quantitative PCR (polymerase chain reaction) was
      used to detect the expression levels of TFF-1 and PTEN mRNAs (Messenger
      ribonucleic acids) in the above three endometria, and their relations with
      clinical pathological characteristics were analyzed. The RT-PCR (reverse
      transcription-polymerase chain reaction) was employed to detect the expression
      levels of miR-135b, miR-125b and Snail mRNAs in the three endometria, and their
      correlations with the expressions of TTF-1 and PTEN mRNAs, were analyzed.
      RESULTS: The expression levels of TFF-1 and PTEN mRNAs in endometrial cancer
      tissues were significantly lower than those in the other two groups, while those
      in normal endometrium tissues were the highest, and the differences were
      statistically significant (p < 0.05). There were no significant differences in
      the menstruation status and the expression levels of TFF-1 and PTEN mRNAs between
      adenocarcinoma and squamous carcinoma (p > 0.05). With the increase of FIGO
      (International Federation of Gynecology and Obstetrics) stage and depth of
      invasion, as well as the metastasis of pelvic lymph nodes, the expression levels
      of TFF-1 and PTEN mRNAs were significantly decreased, and the differences were
      statistically significant (p < 0.05). The expression level of miR-135b mRNA in
      endometrial cancer was significantly higher than that in the other two groups,
      while that in normal endometrium was the lowest. The expression levels of miR
      125b and Snail mRNAs were significantly lower than those in the other two groups,
      while those in normal endometrium were the highest; the differences were
      statistically significant (p < 0.05). Expression levels of TTF-1 and PTEN mRNAs
      were negatively correlated with the expression level of miR-135b mRNA, and
      positively associated with the expression levels of miR-125b and Snail mRNAs (p <
      0.05). The results from the ROC (Receiver Operating Characteristic) model showed
      that, for the diagnosis of endometrial cancer with TTF-1 mRNA, the sensitivity
      was 86.5%, the specificity was 84.2%, the accuracy (area under curve - AUC) was
      0.823, 95% CI (confidence intervals) = 0.762-0.921, p = 0.012. For the diagnosis
      of endometrial cancer with PTEN mRNA, the sensitivity was 85.3%, the specificity
      was 83.6%, the accuracy was 0.842, 95% CI = 0.785-0.936, p = 0.010. CONCLUSIONS:
      TTF-1 and PTEN can be used as molecular markers for the early diagnosis of
      endometrial cancer, which are closely related to clinical features and may affect
      tumor progression by regulating the proliferation activity of tumor cells.

PMID- 28745798
TI  - Research on apoptotic signaling pathways of recurrent spontaneous abortion caused
      by dysfunction of trophoblast infiltration.
AB  - OBJECTIVE: To study the apoptotic signaling pathways of recurrent spontaneous
      abortion caused by dysfunction of trophoblast infiltration. PATIENTS AND METHODS:
      60 patients with recurrent spontaneous abortion and normal abortion were selected
      consecutively as recurrent spontaneous abortion group and abortion group,
      respectively. Villous tissues were obtained and cell apoptosis was observed under
      a microscope; terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end
      labeling (Tunel) method was used to test the apoptosis rate. In situ
      hybridization was adopted to detect expressions of Fas messenger RNA (Fas mRNA)
      and Fas ligand messenger RNA (FasL mRNA); expression of Fas, FasL and protein
      kinase C (PKC) were examined by immunohistochemistry at protein level;
      fluorescence spectrophotometer was used to test Ca2+ level. RESULTS: The
      apoptosis rate, expressions of Fas mRNA, and FasL mRNA, expressions of Fas and
      FasL proteins, as well as Ca2+ level, were significantly higher in the recurrent
      spontaneous abortion group than in abortion group. The level of PKC protein was
      significantly lower in recurrent spontaneous abortion group than in abortion
      group (p<0.05). CONCLUSIONS: Fas-FasL and PKC signaling pathways, as well as
      Ca2+, may mediate the dysfunction of trophoblast infiltration, which leads to
      recurrent spontaneous abortion.

PMID- 28745799
TI  - Efficacy of femoral nail anti-rotation of helical blade in unstable
      intertrochanteric fracture.
AB  - OBJECTIVE: We analyzed the comparative efficacy and long-term prognosis with
      proximal femoral nail anti-rotation (PFNA) and dynamic hip screw (DHS) for the
      treatment of unstable intertrochanteric fractures, retrospectively. We determined
      the independent risk factors to guide subsequent surgery and improve the long
      term quality of life. PATIENTS AND METHODS: We selected 165 patients suffering
      from unstable intertrochanteric fracture from January 2010 to January 2015 in our
      hospital, including 89 treated with PFNA and 76 with DHS surgery. The duration of
      follow-up lasted from 10 months to 56 months (34.7 +/- 8.5) on average. The
      patient demographics included gender, age, reasons for fracture, fracture type
      (Evans-Jensen), fracture time, comorbidities, surgical procedures (PFNA and DHS),
      the number of internal fixations, length, surgical time, blood loss,
      postoperative drug therapy, time for auxiliary external fixation and
      postoperative weight duration. The final indicators included adverse effects
      associated with implants; postoperative complications, clinical healing or bone
      healing time and functional score (Harris hip joint function scale,
      fine/excellent rate). RESULTS: The differences in gender, age, fracture reasons,
      fracture type, fracture time and comorbidities were not statistically significant
      between the groups (p>0.05). However, the number of internal fixations, length,
      surgical time and blood loss, postoperative drug combination, time for auxiliary
      external fixation and postoperative weight duration were statistically
      significant (p<0.05). The effect of PFNA was more significant than that of DHS
      group. The prevalence of complications was reduced significantly. The patients
      treated with PFNA scored significantly higher on the Harris hip joint function
      scale than the DHS group (p<0.05). The independent risk factors affecting healing
      after surgery included fracture type, fracture time, different surgical
      procedures, the number of internal fixations and length. The independent risk
      factors affecting the follow-up Harris hip score included age, fracture type,
      comorbidities, different surgical procedures, postoperative drug combination,
      auxiliary external fixation, application time and postoperative weight duration.
      CONCLUSIONS: Compared with DHS, PFNA resulted in better clinical outcomes and
      long-term prognosis of unstable intertrochanteric fractures.

PMID- 28745800
TI  - Experimental study on repairing skin defect by tissue-engineered skin substitute
      compositely constructed by adipose-derived stem cells and fibrin gel.
AB  - OBJECTIVE: To study the application value of artificial skin substitute
      compositely constructed by adipose-derived stem cells and fibrin gel in skin
      defect. MATERIALS AND METHODS: Adipose-derived stem cells (ADSCs) were obtained
      from healthy pure green fluorescent protein (GFP) transgenic mice and were proved
      to have multiple differentiation potentials. They compositely constructed
      artificial skin substitute in vitro with fibrin gel. 24 SD rats of either gender,
      with the gestational age of 3-5 weeks, were divided into four groups in the
      experiment, namely model group (autologous skin flap transplantation), adipose
      derived stem cell transplantation group, fibrin gel transplantation group and
      compound transplantation group, 6 rats for each group. At the skin blood flow
      (measured by applying laser Doppler rheometer) and survival rate of the flap on
      7d and 21d respectively, the materials were transplanted at back skin injury (1
      cm*1 cm) to prepare tissue slice for routine HE staining. The conditions of wound
      healing were observed, and the angiogenesis of flap neovascularization was
      detected by the immunofluorescent assay. RESULTS: The skin blood flow, the
      survival rate of flap and density of neovascularization 7d and 21d after
      transplantation were significantly higher than those of stem cell group, followed
      by the model group, with the lowest ones in the fibrin gel group. The differences
      had statistical significance (p<0.05). The wound healing time of compound group
      was significantly shorter than that of stem cell group, followed by the model
      group, with the longest one in the fibrin gel group. The differences had
      statistical significance (p<0.05). CONCLUSIONS: The artificial skin substitute
      compositely constructed by adipose-derived stem cells and fibrin gel could
      significantly shorten healing time and improve the survival rate of the flap in
      skin defect, with better application value.

PMID- 28745801
TI  - Flumazenil versus placebo or no intervention for people with cirrhosis and
      hepatic encephalopathy.
AB  - BACKGROUND: Hepatic encephalopathy is a common complication of cirrhosis which
      results in poor brain functioning. The spectrum of changes associated with
      hepatic encephalopathy ranges from the clinically 'indiscernible' or minimal
      hepatic encephalopathy to the clinically 'obvious' or overt hepatic
      encephalopathy. Flumazenil is a synthetic benzodiazepine antagonist with high
      affinity for the central benzodiazepine recognition site. Flumazenil may benefit
      people with hepatic encephalopathy through an indirect negative allosteric
      modulatory effect on gamma-aminobutyric acid receptor function. The previous
      version of this review, which included 13 randomised clinical trials, found no
      effect of flumazenil on all-cause mortality, based on an analysis of 10
      randomised clinical trials, but found a beneficial effect on hepatic
      encephalopathy, based on an analysis of eight randomised clinical trials.
      OBJECTIVES: To evaluate the beneficial and harmful effects of flumazenil versus
      placebo or no intervention for people with cirrhosis and hepatic encephalopathy.
      SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials
      Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and LILACS;
      meeting and conference proceedings; and bibliographies in May 2017. SELECTION
      CRITERIA: We included randomised clinical trials regardless of publication
      status, blinding, or language in the analyses of benefits and harms, and
      observational studies in the assessment of harms. DATA COLLECTION AND ANALYSIS:
      Two review authors extracted data independently. We undertook meta-analyses and
      presented results using risk ratios (RR) with 95% confidence intervals (CI) and
      I2 values as a marker of heterogeneity. We assessed bias control using the
      Cochrane Hepato-Biliary Group domains; determined the quality of the evidence
      using GRADE; evaluated the risk of small-study effects in regression analyses;
      and conducted trial sequential, subgroup, and sensitivity analyses. MAIN RESULTS:
      We identified 14 eligible randomised clinical trials with 867 participants, the
      majority of whom had an acute episode of overt hepatic encephalopathy. In
      addition, we identified one ongoing randomised clinical trial. We were unable to
      gather outcome data from 2 randomised clinical trials with 25 participants. Thus,
      our analyses include 842 participants from 12 randomised clinical trials
      comparing flumazenil versus placebo. We classified one randomised clinical trial
      at low risk of bias in the overall assessment and the remaining randomised
      clinical trials at high risk of bias. The duration of follow-up ranged from a few
      minutes to two weeks, but it was less than one day in the majority of the
      trials.In total, 32/433 (7.4%) participants allocated to flumazenil versus 38/409
      (9.3%) participants allocated to placebo died (RR 0.75, 95% CI 0.48 to 1.16; 11
      randomised clinical trials; low quality evidence). The Trial Sequential Analysis
      and the one randomised clinical trial assessed as low risk of bias (RR 0.76, 95%
      CI 0.37 to 1.53) found no beneficial or harmful effects of flumazenil on all
      cause mortality. The methods used to evaluate hepatic encephalopathy included
      several different clinical scales, electrophysiological variables, and
      psychometric tests. Flumazenil was associated with a beneficial effect on hepatic
      encephalopathy when including all randomised clinical trials (RR 0.75, 95% CI
      0.71 to 0.80; 824 participants; 9 randomised clinical trials; low quality
      evidence), or just the trial at low risk of bias (RR 0.78, 95% CI 0.72 to 0.84;
      527 participants). The Trial Sequential Analysis supported a beneficial effect of
      flumazenil on hepatic encephalopathy. The randomised clinical trials included
      little information about causes of death and little information on non-fatal
      serious adverse events. AUTHORS' CONCLUSIONS: We found low quality evidence
      suggesting a short-term beneficial effect of flumazenil on hepatic encephalopathy
      in people with cirrhosis, but no evidence of an effect on all-cause mortality.
      Additional evidence from large, high quality randomised clinical trials is needed
      to evaluate the potential benefits and harms of flumazenil in people with
      cirrhosis and hepatic encephalopathy.

PMID- 28745802
TI  - Progressive subglottic stenosis in a child with Pallister-Killian syndrome.
AB  - Pallister-Killian syndrome (PKS) is rare genetic disorder caused by tetrasomy 12p
      mosaicism with supernumerary isochromosome 12p that manifests with intellectual
      disability, craniofacial dysmorphism, and epilepsy. Although PKS presents as a
      multisystem morphological defect, respiratory system involvement is rare, except
      for diaphragmatic hernia. We are the first to report a case of PKS with
      progressive subglottic stenosis. Subglottic stenosis is a potentially lethal
      condition due to severe respiratory obstruction and difficult intubation;
      therefore, further accumulation of cases is required to assess the causal link
      between PKS and subglottic stenosis.

PMID- 28745803
TI  - Measuring socioeconomic inequalities in the use of dental care services among
      older adults in Brazil.
AB  - OBJECTIVES: The primary objectives are to assess socioeconomic inequality in the
      use of dental care among older Brazilian adults and to analyse the extent to
      which certain determinants contribute to that inequality. METHODS: A cross
      sectional study using data from the National Oral Health Survey conducted in
      2010. All individuals answered a structured questionnaire containing questions on
      their use of dental care and socioeconomic conditions and underwent a clinical
      oral examination by a dentist. Concentration indices were decomposed to determine
      the contribution of socioeconomic factors to inequalities. RESULTS: Being in the
      fifth wealth, quintile was associated with higher odds of having recently visited
      a dentist (reference: 1st quintile, odds-ratio (OR) 2.26, 95% confidence interval
      (CI) 1.51-3.38). In addition, being in the top two quintiles of wealth was
      negatively associated with the use of public dental services. Having eight or
      more years of schooling was associated with higher odds of both having a recent
      dental visit and receiving preventive care (relative to having 0-3 years of
      education), and negatively associated with using public dental services. Results
      indicate pro-rich inequalities in recent dental visits and preventive dental
      care. Further, there was a pro-poor inequality in the use of public dental care
      services. CONCLUSIONS: The recent use of dental care and the use of preventive
      care are disproportionately concentrated among wealthier older adults, whereas
      the use of public services is more common among poorer individuals. Wealth
      inequalities in dental care use were mainly explained by socioeconomic factors,
      such as wealth and education, rather than oral health factors, such as needing
      treatment or a dental prosthesis.

PMID- 28745804
TI  - Postprostatectomy incontinence is related to pelvic floor displacements observed
      with trans-perineal ultrasound imaging.
AB  - AIMS: To investigate the relationship between post-prostatectomy incontinence and
      dynamic features of activation of specific pelvic floor muscles in addition to
      anatomical parameters of the urethra. METHODS: Forty-two men aged 66 (7) years
      (incontinent [N = 19] and continent [N = 23]) who had undergone prostatectomy
      participated. Transperineal ultrasound imaging was used to record sagittal images
      of pelvic structures during involuntary coughing and sustained maximal voluntary
      contractions. Imaging data were analyzed to calculate displacements of pelvic
      floor landmarks associated with activation of the puborectalis, striated urethral
      sphincter, and bulbocavernosus muscles. Anatomical features of functional
      urethral length and the resting position of the ano-rectal and urethra-vesical
      junctions were calculated. A principal component analysis and multiple logistic
      regression were used to consider which combinations of variables best distinguish
      between men with and without incontinence. RESULTS: Five principal components
      were identified that together explained 72.0% of the data. Two principal
      components that represented (i) striated urethral sphincter activation and (ii)
      bulbocavernosus and puborectalis muscle activation were significantly different
      between participants with and without incontinence. Together these components
      correctly identified 88.1% of incontinent men, with a specificity and sensitivity
      of 91.3% and 84.2%, respectively. Poor function of the bulbocavernosus and
      puborectalis muscles could be compensated by good striated urethral sphincter
      function, but the bulbocavernosus and puborectalis muscles had less potential to
      compensate for poor striated urethral sphincter function. CONCLUSIONS: Dynamic
      features of pelvic floor muscle activation, particularly shortening of the
      striated urethral sphincter during cough and voluntary contraction, are related
      to continence status after prostatectomy.

PMID- 28745805
TI  - TAC-302 promotes neurite outgrowth of isolated peripheral neurons and prevents
      bladder denervation related bladder dysfunctions following bladder outlet
      obstruction in rats.
AB  - AIMS: To evaluate the ability of TAC-302, a cyclohexenoic fatty alcohol
      derivative, to enhance neurite outgrowth in cultured rat dorsal root ganglion
      (DRG) neurons, and the preventive effects of TAC-302 on bladder denervation
      related storage and voiding dysfunctions in rats with bladder outlet obstruction
      (BOO). METHODS: Rat DRG neurons were cultured in the presence of TAC-302. Cell
      numbers and neurite lengths were quantified after a 24 h culture. BOO was
      achieved by partial ligature of the proximal urethra in female rats. BOO rats
      were divided into three groups and orally treated with vehicle of 3 or 30 mg/kg
      TAC-302 twice a day for 4 weeks. Cystometry was performed under conscious
      conditions. Immunohistochemical staining using anti-PGP9.5 of the bladder muscle
      layer was performed, and the innervation area was scored. RESULTS: TAC-302
      significantly and dose-dependently increased neurite outgrowth in cultured DRG
      neurons. BOO rats showed a decreased innervation area in the urinary bladder
      compared to sham-operated rats. BOO-induced denervation of the urinary bladder
      was partially prevented by oral treatment with TAC-302. TAC-302 significantly
      reduced the frequency of non-voiding contraction (NVC) and residual urine volume
      (RUV) compared with the BOO vehicle group (P < 0.05). The innervation area score
      exhibited significant negative correlations with NVC and RUV, indicating that
      they increased according to the progression of denervation. CONCLUSIONS: Our data
      indicate that TAC-302 promotes neurite outgrowth in vitro. In addition, TAC-302
      prevents BOO-induced bladder dysfunction in rats, and has a protective effect on
      bladder denervation.

PMID- 28745806
TI  - Detection and quantification of overactive bladder activity in patients: Can we
      make it better and automatic?
AB  - AIMS: To explore the use of time-frequency analysis as an analytical tool to
      automatically detect pattern changes in bladder pressure recordings of patients
      with overactive bladder (OAB). To provide quantitative data on the bladder's non
      voiding activity which could improve the current diagnosis and potentially the
      treatment of OAB. METHODS: We developed an algorithm, based on time-frequency
      analysis, to analyze bladder pressure during the filling phase of urodynamic
      studies. The algorithm was used to generate a bladder overactivity index (BOI)
      for a quantitative estimation of the average bladder non-voiding-activity. We
      tested the algorithm with one control group and two groups of patients with OAB
      symptoms: one group with detrusor overactivity (DO), assessed by an experienced
      urologist (OAB-with-DO group), and another group for which detrusor overactivity
      was not diagnosed (OAB-without-DO group). RESULTS: The algorithm identified
      diagnostically significant data on the bladder non-voiding activity in a
      specified frequency range. BOI was significantly higher for both OAB groups
      compared to the control group: the median value of BOI was twice as big in OAB
      without-DO and more than four times higher in OAB-with-DO compared to control
      group. Moreover the algorithm was successfully tested to detect episodes of
      detrusor overactivity. CONCLUSIONS: We have shown that a simple algorithm, based
      on time-frequency analysis of bladder pressure, may be a promising tool in the
      clinical setting. The algorithm can provide quantitative data on non-voiding
      bladder activity in patients and quantify the changes according to phenotype.
      Moreover the algorithm can detect DO, showing potential for triggering
      conditional bladder stimulation.

PMID- 28745807
TI  - Long-term outcomes and risks factors for failure of intradetrusor
      onabotulinumtoxin A injections for the treatment of refractory neurogenic
      detrusor overactivity.
AB  - AIMS: Aims of this study were to assess the long-term outcomes of Intradetrusor
      injection of OnabotulinumtoxinA (Botox(r) injection) associated with clean
      intermittent-catheterization (CIC) for the treatment of neurogenic detrusor
      overactivity (NDO) and to identify risk factors for failure. METHODS:
      Neurological patients with NDO using CIC who had received Botox(r) injections
      between January 2001 and September 2013 were included. Clinical, urodynamic and
      radiological data were recorded. Primary endpoint was failure and withdrawal
      rates after 3, 5, and 7 years of management. Survival curves of withdrawals and
      failures of treatment were calculated with a 95-confidence interval using the
      Kaplan-Meier method. Risk factors for failure were determined with univariate
      analysis and multivariate analysis using Cox model. RESULTS: Overall, 292
      patients, mean age of 40 +/- 13, 6 years, were included. Overall, 219 patients
      (80.6%; IC95% [76.3-85.4%]) were still treated with Botox(r) injections after 3
      years, 128 (71.1%; IC95% [65.7%, 76.9%]) after 5 years, and 58 (60.8%, IC95%
      [54.0%, 68.4%]) after 7 years. Failure rate was 12.6% (IC95% [8.6-16.5%]) after 3
      years, 22.2% (IC95% [16.6-27.3%]) after 5 years, and 28.9% (IC95% [21.9%; 35.3%])
      after 7 years of follow-up. Withdrawal rate after 7 years of follow-up was 11.3%
      (n = 33/292). Severe NDO at baseline appears to be a significant risk factor for
      failure. CONCLUSION: This study confirms long-term efficacy and tolerance of
      Botox(r) injection in patients with NDO using CIC. Long-term failure and
      withdrawal rates remain low but significant, and need to be managed.

PMID- 28745808
TI  - Hypophysitis, Panhypopituitarism, and Hypothalamitis in a Scottish Terrier Dog.
AB  - A 6-year old male neutered Scottish Terrier was referred with a 1 week history of
      progressive lethargy and anorexia. Neurological examination localized a lesion to
      the forebrain and hormonal testing showed panhypopituitarism. Magnetic resonance
      imaging (MRI) of the brain revealed a rounded, well-defined, suprasellar central
      mass. The mass was slightly hyperintense to the cortical grey matter on T2
      weighted (T2W), hypointense on T1-weighted (T1W) images and without T2* signal
      void. There was a central fusiform enhancement of the mass after contrast
      administration which raised the suspicion of a pituitary neoplasm. Rapid
      deterioration of the dog prevented further clinical investigations.
      Histopathologic examination revealed a lymphocytic panhypophysitis of unknown
      origin suspected autoimmune involving the hypothalamus (hypothalamitis). This is
      a unique case report of a dog presenting with inflammatory hypophysitis and
      hypothalamitis of suspected autoimmune origin with detailed clinical, MRI,
      histology and immunohistochemistry findings.

PMID- 28745809
TI  - Rural-urban differentials in the rates and factors associated with post-neonatal
      mortality in Nigeria: Evidence from the 2013 national household survey.
AB  - BACKGROUND: The burden of post-neonatal mortality remains considerably high in
      Nigeria. This study examines the rural-urban differences in post-neonatal
      mortality rates (PNMR) and associated factors in Nigeria. METHODS: Dataset from
      the 2013 Nigeria demographic and health survey, disaggregated by rural-urban
      residence, was analyzed. PNMR was reported using frequency tabulation, whereas,
      factors associated were first evaluated using Chi-Square test and further
      examined using multivariable logistic regression analysis. RESULTS: A total of
      30384 singleton livebirths (20449 in rural and 9935 in urban residences) in the
      five years preceding the survey was included in this study. PNMR in rural and
      urban residences were 34 (95%CI: 31 - 38) and 22 (95%CI: 18 - 26) deaths per 1000
      live births (P<0.001), respectively. In rural residence, living in the South-West
      region reduced the odds of post-neonatal mortality by 63% (Adjusted OR [AOR]:
      0.372, 95%CI: 0.187 - 0.732)). In urban residence, poor wealth index (AOR: 1.660,
      95%CI: 1.024 - 2.689), living in the South-East region (AOR: 2.902, 95%CI: 1.470 
      5.726), and home delivery (AOR: 1.539, 95%CI: 1.016 - 2.330) increased the odds
      of post-neonatal mortality. Regardless of residence, the use of solid cooking
      fuels (Rural: AOR: 2.394, 95%CI: 1.211 - 4.734; Urban: AOR: 1.912, 95%CI: 1.206 -
      3.030), birth interval < 24 months (Rural: AOR: 1.880, 95%CI: 1.557 - 2.270;
      Urban: AOR: 1.630, 95%CI: 1.042 - 2.550) and lack of breastfeeding (Rural: AOR:
      2.547, 95%CI: 2.089 - 3.105; Urban: AOR: 2.152, 95%CI: 1.496 - 3.096) increased
      the odds of post-neonatal mortality. CONCLUSION: PNMR and associated factors
      differ in rural and urban Nigeria. Post-neonates in urban areas had better
      survival chances. Intervention efforts would need to prioritize findings in this
      study. This article is protected by copyright. All rights reserved.

PMID- 28745810
TI  - Flow cytometry vs optical microscopy in the evaluation of the genotoxic potential
      of xenobiotic compounds.
AB  - BACKGROUND: It is now recognized that mutational events play a key role in the
      development of pathological processes like cancer, cardiovascular, and
      neurodegenerative disease. Therefore, it is crucial to have Genetics Toxicology
      tests that allow rapid and accurate identification of the mutagenic potential of
      a xenobiotic. Currently the most widely used technique is the "In vitro mammalian
      cell micronucleus test" performed by optical microscopy, but some problems have
      been highlighted, including the number of cells analyzed, the high subjectivity
      of the reading at the microscope and the long analysis times. AIM: The aim of
      this work was to develop a study protocol, for the automation of the "In vitro
      mammalian cell micronucleus test", by flow cytometry (FCM) analysis, to overcome
      the limits that afflict the optical microscopy. METHODS: The study was conducted
      on peripheral blood lymphocytes treated with three known clastogens and three
      known aneugens. RESULTS: The results obtained by the proposed FCM technique
      compared with those obtained through the validated method, demonstrated that the
      increase of micronuclei percentage is perfectly comparable between the two
      methods. CONCLUSIONS: This fact, in view of results supported by a high number of
      cells analyzed and obtained by an accurate and objective reading, with a
      considerable reduction of the analysis time, can support a future request for
      validation of the micronucleus analysis by FCM. (c) 2017 International Clinical
      Cytometry Society.

PMID- 28745811
TI  - Photo- and Thermoresponsive Dehydration of Spiropyran-Functionalized Polymer
      Regulated by Molecular Recognition.
AB  - The photo- and thermoresponse of poly(N-isopropylacrylamide) (pNIPAAm)
      functionalized with spiropyran chromophore is examined with respect to the
      influence of molecular recognition by cyclodextrin (CD). Characterization in
      aqueous solutions of spiropyran-functionalized poly(N,N-dimethylacrylamide) under
      coexistence of alpha-, beta-, or gamma-CD reveals that beta-CD selectively
      includes the ring-closing isomer of the chromophore, which is dominant under
      light irradiation, while no inclusion is observed for the protonated ring-opening
      isomer, which is dominant in the dark before irradiation. As a result, it is
      shown that the selective inclusion of the chromophore at a polymer side chain is
      switched by light irradiation. Further, drastic photoresponsive dehydration of
      spiropyran-functionalized pNIPAAm is inhibited only by beta-CD out of three
      examined CDs, demonstrating that the molecular recognition regulates the
      dehydration of the whole polymer triggered by the photoswitching of the
      chromophore introduced at only 1 mol% functionalization.

PMID- 28745812
TI  - Neuronal control of experimental colitis occurs via sympathetic intestinal
      innervation.
AB  - BACKGROUND: Vagus nerve stimulation is currently clinically evaluated as a
      treatment for inflammatory bowel disease. However, the mechanism by which this
      therapeutic intervention can have an immune-regulatory effect in colitis remains
      unclear. We determined the effect of intestine-specific vagotomy or intestine
      specific sympathectomy of the superior mesenteric nerve (SMN) on dextran sodium
      sulfate (DSS)-induced colitis in mice. Furthermore, we tested the efficacy of
      therapeutic SMN stimulation to treat DSS-induced colitis in rats. METHODS: Vagal
      and SMN fibers were surgically dissected to achieve intestine-specific vagotomy
      and sympathectomy. Chronic SMN stimulation was achieved by implantation of a cuff
      electrode. Stimulation was done twice daily for 5 minutes using a biphasic pulse
      (10 Hz, 200 MUA, 2 ms). Disease activity index (DAI) was used as a clinical
      parameter for colitis severity. Colonic cytokine expression was measured by
      quantitative PCR and ELISA. KEY RESULTS: Intestine-specific vagotomy had no
      effect on DSS-induced colitis in mice. However, SMN sympathectomy caused a
      significantly higher DAI compared to sham-operated mice. Conversely, SMN
      stimulation led to a significantly improved DAI compared to sham stimulation,
      although no other parameters of colitis were affected significantly. CONCLUSIONS
      & INFERENCES: Our results indicate that sympathetic innervation regulates the
      intestinal immune system as SMN denervation augments, and SMN stimulation
      ameliorates DSS-induced colitis. Surprisingly, intestine-specific vagal nerve
      denervation had no effect in DSS-induced colitis.

PMID- 28745813
TI  - Subversion of innate immune responses by Francisella involves the disruption of
      TRAF3 and TRAF6 signalling complexes.
AB  - The success of pathogens depends on their ability to circumvent immune defences.
      Francisella tularensis is one of the most infectious bacteria known. The
      remarkable virulence of Francisella is believed to be due to its capacity to
      evade or subvert the immune system, but how remains obscure. Here, we show that
      Francisella triggers but concomitantly inhibits the Toll-like receptor, RIG-I
      like receptor, and cytoplasmic DNA pathways. Francisella subverts these pathways
      at least in part by inhibiting K63-linked polyubiquitination and assembly of
      TRAF6 and TRAF3 complexes that control the transcriptional responses of pattern
      recognition receptors. We show that this mode of inhibition requires a functional
      type VI secretion system and/or the presence of live bacteria in the cytoplasm.
      The ability of Francisella to enter the cytosol while simultaneously inhibiting
      multiple pattern recognition receptor pathways may account for the notable
      capacity of this bacterium to invade and proliferate in the host without evoking
      a self-limiting innate immune response.

PMID- 28745814
TI  - Ocular localization of mycobacterial lesions in tank-reared juvenile cobia,
      Rachycentron canadum.
AB  - Severe clinical mycobacteriosis with consistent ocular lesion localization was
      diagnosed in a population of 800 juvenile tank-reared Cobia (Rachycentron
      canadum) which experienced a sudden increase in mortality approximately 5 months
      after arriving into Trinidad and Tobago from Florida, USA. Moderate daily
      mortality (15-20 animals per day) persisted for just over 1 month. Moribund fish
      displayed circling behaviour and had an open-mouth gape upon death. Fish
      consistently presented with bilateral exophthalmia, corneal cloudiness and
      hyphema. Non-branching acid-fast rods were detected in aqueous humour touch
      preparations. Histological analysis revealed severe bilateral intra-ocular
      granulomatous responses in all specimens. Mycobacterium sp. was identified using
      a real-time PCR assay detecting the RNA polymerase beta-subunit (rpoB) gene in
      different tissue samples. Specimens did not present with characteristic
      granulomatous responses usually seen in viscera. To the best of our knowledge,
      this represents only the third documentation of piscine mycobacterial infection
      presenting with only localized ocular lesions, and the second documented case of
      mycobacteriosis in cobia. It is, however, the first documentation of an ocular
      presentation of mycobacteriosis in a marine species and is the first
      documentation of such a presentation in cobia.

PMID- 28745815
TI  - Robust Cooperative Photo-oxidation of Sulfides without Sacrificial Reagent under
      Air Using a Dinuclear RuII -CuII Assembly.
AB  - A molecular chromophore-catalyst assembly containing a chromophore ruthenium(II)
      center (RuIIchro ) and a catalytic copper(II) center (CuIIcat ) has been prepared
      easily. The assembly was employed for photocatalytic oxidation of sulfides
      without sacrificial reagent in the presence of dioxygen under blue light
      irradiation. Unprecedented turnover number (TON) up to 32 000 was achieved. It
      was elucidated that an electron transferred from excited state of chromophore
      RuII*chro to CuIIcat along with generation of CuIcat that was further activated
      by O2 . These results demonstrate a promising strategy for efficient cooperative
      photocatalytic reactions under air using the chromophore-catalyst assembly.

PMID- 28745816
TI  - The role of TACC3 in mitotic spindle organization.
AB  - TACC3 regulates spindle organization during mitosis and also regulates centrosome
      mediated microtubule nucleation by affecting gamma-Tubulin ring complexes. In
      addition, it interacts with different proteins (such as ch-TOG, clathrin and
      Aurora-A) to function in mitotic spindle assembly and stability. By forming the
      TACC3/ch-TOG complex, TACC3 acts as a plus end-tracking protein to promote
      microtubule elongation. The TACC3/ch-TOG/clathrin complex is formed to stabilize
      kinetochore fibers by crosslinking adjacent microtubules. Furthermore, the
      phosphorylation of TACC3 by Aurora-A is important for the formation of TACC3/ch
      TOG/clathrin and its recruitment to kinetochore fibers. Recently, the aberrant
      expression of TACC3 in a variety of human cancers has been linked with mitotic
      defects. Thus, in this review, we will discuss our current understanding of the
      biological roles of TACC3 in mitotic spindle organization.

PMID- 28745817
TI  - Solvent-Free Synthesis of Uniform MOF Shell-Derived Carbon Confined SnO2 /Co
      Nanocubes for Highly Reversible Lithium Storage.
AB  - Tin dioxide (SnO2 ) has attracted much attention in lithium-ion batteries (LIBs)
      due to its abundant source, low cost, and high theoretical capacity. However, the
      large volume variation, irreversible conversion reaction limit its further
      practical application in next-generation LIBs. Here, a novel solvent-free
      approach to construct uniform metal-organic framework (MOF) shell-derived carbon
      confined SnO2 /Co (SnO2 /Co@C) nanocubes via a two-step heat treatment is
      developed. In particular, MOF-coated CoSnO3 hollow nanocubes are for the first
      time synthesized as the intermediate product by an extremely simple thermal solid
      phase reaction, which is further developed as a general strategy to successfully
      obtain other uniform MOF-coated metal oxides. The as-synthesized SnO2 /Co@C
      nanocubes, when tested as LIB anodes, exhibit a highly reversible discharge
      capacity of 800 mAh g-1 after 100 cycles at 200 mA g-1 and excellent cycling
      stability with a retained capacity of 400 mAh g-1 after 1800 cycles at 5 A g-1 .
      The experimental analyses demonstrate that these excellent performances are
      mainly ascribed to the delicate structure and a synergistic effect between Co and
      SnO2 . This facile synthetic approach will greatly contribute to the development
      of functional metal oxide-based and MOF-assisted nanostructures in many frontier
      applications.

PMID- 28745818
TI  - Is repeat Botulinum Toxin A injection valuable for neurogenic detrusor
      overactivity-A systematic review and meta-analysis.
AB  - AIM: To investigate the value of repeat botulinum toxin A (BTX-A) injections in
      patients with neurogenic detrusor overactivity (NDO). METHODS: We searched the
      PubMed, EMBASE, and EBSCO databases for articles published until June 2016.
      Studies that reported the efficacy and safety of repeat BTX-A injections for
      adult patients with NDO were eligible. The effect size for each outcome was
      calculated as the standardized mean difference +/- standard error and 95%
      confidence interval, and was graded as small, >0.2; moderate, >0.5; or large,
      >0.8. The outcomes included maximum cystometric capacity (MCC), maximum detrusor
      pressure (MDP), reflex volume (RV), bladder compliance (BC), quality of life
      (QOL), and injection interval. Descriptive reviews were performed for urinary
      incontinence (UI) and adverse events (AEs). RESULTS: Eighteen studies involving
      1533 patients whose level of evidence ranged from 3 to 4 were included in this
      study. We noted non-significant changes in MCC, MDP, RV, and BC between the first
      and last injections. Patients who had received <=4 injections were found to have
      stable QOL improvements after the first and last injections, whereas patients who
      had received >=5 injections were found to have a significant decrease in QOL
      after the last injection. No significant differences in injection intervals were
      noted after repeat BTX-A injections, and the repeat injection failure rate was
      low. CONCLUSION: Our study demonstrated that repeat BTX-A injections allow
      sustained improvements in patients with NDO. The rate of AEs was stable and low.
      However, additional high-quality, large-scale, and long-term trials are necessary
      to establish the efficacy and safety of >=5 repeat BTX-A injections.

PMID- 28745819
TI  - Rapid and sensitive detection of redspotted grouper nervous necrosis virus
      (RGNNV) infection by aptamer-coat protein-aptamer sandwich enzyme-linked apta
      sorbent assay (ELASA).
AB  - Redspotted grouper nervous necrosis virus (RGNNV) is one of the most devastating
      pathogens in the aquaculture of the grouper, Epinephlus sp., worldwide. The early
      and rapid diagnosis of RGNNV is important for the prevention of RGNNV infection.
      In this study, an aptamer (A10)-based sandwich enzyme-linked apta-sorbent assay
      (ELASA) was developed for RGNNV diagnosis. This sandwich ELASA showed high
      specificity for the RGNNV coat protein (CP) and virions in virus-infected cells
      and tissues. At the optimized working concentration of 200 nM of aptamer, the
      ELASA could detect RGNNV in the lysates of as few as 4 * 103 RGNNV-infected GB
      cells. Incubation for 10 min was sufficient to produce accurate results. The
      sandwich ELASA was most stable at incubation temperatures of 4-25 degrees C, but
      could still distinguish RGNNV-infected samples from the controls at 37 degrees C.
      It could detect RGNNV infection in brain lysates diluted 1/10, with results
      consistent with those of reverse transcription PCR, although with 10% less
      sensitivity. The main equipment required includes dissection tools, a water bath,
      PierceTM Streptavidin Coated Plates and a microplate reader. The sandwich ELASA
      has great potential utility for the rapid and sensitive diagnosis of RGNNV in its
      early stages by fish farmers.

PMID- 28745820
TI  - Recovery of Bacillus mycoides, B. pseudomycoides and Aeromonas hydrophila from
      common carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) with gill
      disease.
AB  - During a 3-month period from June to the end of August 2016, ~5% mortalities were
      observed in a farm with rainbow trout (Oncorhynchus mykiss Walbaum) and one farm
      of common carp (Cyprinus carpio L.) in Bulgaria. The disease was manifested by
      gill ulcers/rot, asphyxiation and bloody ascites. Aeromonas hydrophila was
      isolated from the internal organs of all the diseased fish. Bacillus mycoides or
      B. pseudomycoides were recovered from the gill lesions on diseased carp and
      rainbow trout, respectively, with identification achieved by conventional
      phenotyping and by sequencing of the 16S rRNA gene. In vivo experiments confirmed
      that all three organisms were pathogenic to rainbow trout.

PMID- 28745821
TI  - Comparative pathogenesis of piscirickettsiosis in Atlantic salmon (Salmo salar
      L.) post-smolt experimentally challenged with LF-89-like and EM-90-like
      Piscirickettsia salmonis isolates.
AB  - Piscirickettsiosis (SRS) is the most prevalent bacterial disease in Chilean
      salmon aquaculture and is responsible for high economic losses. The aim of this
      study was to comparatively characterize the pathogenesis of SRS in post-smolt
      Atlantic salmon during the early and late stages of infection with
      Piscirickettsia salmonis LF-89-like (PS-LF-89) and EM-90-like (PS-EM-90) using a
      cohabitation challenge. The pathogenesis of cohabitant fish infected with the two
      isolates was relatively different due to cohabitant fish infected with PS-EM-90
      showing higher cumulative mortality and shorter time until death compared with PS
      LF-89 fish. PS-LF-89 caused an SRS infection characterized by kidney and liver
      lesions, whereas PS-EM-90 caused systemic and haemorrhagic disease characterized
      by kidney, liver, heart, brain, skeletal muscle and intestine lesions. Decreased
      serum concentration of total proteins and albumin as well as increased serum ALT,
      AST and creatinine levels in fish infected with both isolates confirmed that
      changes in liver and kidney function occurred during infection. Tissue damage,
      expressed as an SRS histoscore, showed a strong positive correlation with the
      bacterial load expressed as abundance of P. salmonis 16S rRNA transcripts in the
      livers and kidneys of fish affected with either isolate, but the correlation was
      significantly higher in fish infected with PS-EM-90. The results contribute to
      improving the understanding of the bacteria-host interaction.

PMID- 28745822
TI  - DnrI of Streptomyces peucetius binds to the resistance genes, drrAB and drrC but
      is activated by daunorubicin.
AB  - The master regulator, DnrI of Streptomyces peucetius is a member of the family of
      transcriptional activator, Streptomyces antibiotic regulatory proteins (SARP),
      which controls the biosynthesis of antitumor anthracycline, daunorubicin (DNR)
      and doxorubicin (DXR). The binding of DnrI to the heptameric repeat sequence
      found within the -35 promoter region of biosynthetic gene, dpsE activates it. To
      combat the increased level of intracellular DNR, the cell has developed self
      resistance mechanism mediated by drrAB and drrC genes which are regulated by
      regulatory genes. We find that a drug non-producing mutant, DeltadpsA, showed
      sensitive phenotype in plate assay along with an increased level of dnrI
      transcript. Whereas the mutant grown in the presence of DNR showed a resistant
      phenotype with a six and eight folds increase in drrAB and drrC transcripts
      respectively. Computational studies followed by molecular docking showed that
      DnrI bound as a monomer to a slightly modified heptameric DNA motif, 5'-ACACGCA
      in drrA and 5'-ACAACCT in drrC which was also proved by electrophoretic mobility
      shift assay. These findings confirm that DnrI belongs to winged helix-turn-helix
      DNA-binding protein with Tetratricopeptide Repeat domain. The transcriptional
      regulator DnrI binds to the resistance genes at specific sites but they are
      activated only when an increased load of intracellular DNR is sensed.

PMID- 28745823
TI  - Comment on "an endoplasmic reticulum protein, Nogo-B, facilitates alcoholic liver
      disease through regulation of Kupffer cell polarization".

PMID- 28745824
TI  - Gemcitabine combined with cisplatin as adjuvant chemotherapy for non-small cell
      lung cancer: A retrospective analysis.
AB  - BACKGROUND: This study was conducted to evaluate the value of gemcitabine
      combined with cisplatin as adjuvant chemotherapy for radical resection of non
      small cell lung cancer. METHODS: Data of 100 patients who had undergone radical
      resection of non-small cell lung cancer and were treated with
      cisplatin/gemcitabine as adjuvant chemotherapy between June 2007 and December
      2010 at the Chinese Academy of Medical Sciences were reviewed. RESULTS: The
      median age was 59 years (range 36-73); 82% of the patients were male. Forty-two
      percent had adenocarcinoma and 55% had squamous cell carcinoma. Most patients had
      pathologic IIB (29%) and IIIA (44%) stage disease. Eighty-five percent of
      patients completed four cycles of chemotherapy, with 76% completing the planned
      full dose. The main reason for a reduced gemcitabine dose in 13 patients was
      grade 3/4 neutropenia or thrombocytopenia. The median dose and dose intensity
      were 8377.1 mg/m2 and 708 mg/(m2 /week) for gemcitabine and 293.38 mg/m2 and
      25.24 mg/(m2 /week) for cisplatin, respectively. During follow-up the median
      disease-free survival was 33.8 months (95% confidence interval [CI] 15.938
      51.676). Patients with squamous cell carcinoma (hazard ratio [HR] 0.404, 95% CI
      0.241-0.676; P = 0.001) and pathologic stage I (HR 4.379, 95% CI 1.721-11.142; P
      = 0.002) achieved better disease-free survival. The survival rates at one, two,
      and five years were 94%, 77%, and 55%, while the survival rates without
      recurrence were 64%, 53%, and 39%, respectively. CONCLUSION: As an adjuvant
      chemotherapy regimen, gemcitabine with cisplatin is well tolerated. Patients with
      squamous cell carcinomas or pathologic stage I achieve better results.

PMID- 28745825
TI  - Salmonella Choleraesuis outer membrane vesicles: Proteomics and immunogenicity.
AB  - Salmonella enterica serotype Choleraesuis (S. Choleraesuis), Gram-negative
      facultative intracellular pathogen is capable of inducing the cholera in pigs
      whose symptoms manifest as fever, depression, septicemia, arthritis, and
      diarrhea. Infections with S. Choleraesuis has resulted in great economic loss for
      the swine breeding operations. Bacterial outer membrane vesicles (OMVs) play an
      important role in pathogenicity and host-pathogen interaction. In this study, we
      purified OMVs released by S. Choleraesuis strain chi3545 and characterized their
      lipopolysaccharide (LPS) profile. The OMVs contained intact LPS molecules. By
      using LC-MS/MS, we identified 192 proteins in the OMVs. In addition, the
      subcellular location and biological functions of the vesicles was predicted. The
      proteins were mainly derived from outer membranes and cytoplasm. Several proteins
      were immunoreactive and associated with the secretion pathway. Some putative
      multi-drug resistance-associated proteins were also identified. Furthermore,
      immunization experiment via intranasal or intraperitoneal route in mice
      demonstrated that S. Choleraesuis OMVs could elicit strong humoral and mucosal
      immune responses. Although OMVs as vaccine did not provide strong protection
      against clinical strain of wild-type S. Choleraesuis, immunization of OMVs still
      prolonged the survival time of vaccinated mice after high dose of S. Choleraesuis
      infection. Overall, this study provides valuable fundamental information toward
      elucidating the pathogenicity and functions of OMVs secreted from S.
      Choleraesuis.

PMID- 28745826
TI  - Comparison of biuret and refractometry methods for the serum total proteins
      measurement in ruminants.
AB  - BACKGROUND: Determination of serum total protein concentration is commonly
      performed by the biuret method. Refractometric measurement is a faster and less
      expensive alternative but its accuracy has not been determined in ruminants.
      OBJECTIVE: The purpose of the study was to compare the serum total protein
      concentrations in cattle, sheep, and goats measured by the biuret method with
      those obtained by refractometry. METHODS: Serum total protein concentration was
      determined in 120 cattle, 67 sheep, and 58 goat blood samples refractometrically
      and with the biuret method. The data were analyzed with a paired samples t-test,
      and Passing and Bablok regression equations and Bland and Altman plots were
      generated. RESULTS: There was a strong linear relationship between the total
      protein values determined with the refractometer and the biuret method in cattle,
      sheep, and goats. The statistical accuracy, which represents a bias correction
      factor that measures the deviation of the best-fit line from the 45 degrees  line
      through the origin, was 90.63% for cattle, 93.05% for sheep, and 91.76% for
      goats. The mean protein values determined with the refractometer were
      significantly lower than those measured with the biuret method in cattle and
      goats (P < .05) but not in sheep (P > .05). CONCLUSIONS: The evaluated
      refractometer was sufficiently accurate for the determination of serum total
      proteins in cattle, sheep, and goats, although it cannot be used interchangeably
      with the biuret method. The RIs should be corrected for negative bias based on
      the created equations.

PMID- 28745827
TI  - Genetic diversity of catechol 1,2-dioxygenase in the fecal microbial metagenome.
AB  - Catechol 1,2-dioxygenase is the key enzyme that catalyzes the cleavage of the
      aromatic ring of catechol. We explored the genetic diversity of catechol 1,2
      dioxygenase in the fecal microbial metagenome by PCR with degenerate primers. A
      total of 35 gene fragments of C12O were retrieved from microbial DNA in the feces
      of pygmy loris. Based on phylogenetic analysis, most sequences were closely
      related to C12O sequences from Acinetobacter. A full-length C12O gene was
      directly cloned, heterologously expressed in Escherichia coli, and biochemically
      characterized. Purified catPL12 had optimum pH and temperature pH 8.0 and 25 
      degrees C and retained 31 and 50% of its maximum activity when assayed at 0 and
      35  degrees C, respectively. The enzyme was stable at 25 and 37  degrees C,
      retaining 100% activity after pre-incubation for 1 h. The kinetic parameters of
      catPL12 were determined. The enzyme had apparent Km of 67 uM, Vmax of 7.3 U/mg,
      and kcat of 4.2 s-1 for catechol, and the cleavage activities for 3
      methylcatechol, 4-methylcatechol, and 4-chlorocatechol were much less than for
      catechol, and no activity with hydroquinone or protocatechuate was detected. This
      study is the first to report the molecular and biochemical characterizations of a
      cold-adapted catechol 1,2-dioxygenase from a fecal microbial metagenome.

PMID- 28745828
TI  - Incidence of eosinophilic esophagitis in the Netherlands continues to rise: 20
      year results from a nationwide pathology database.
AB  - BACKGROUND: The incidence of eosinophilic esophagitis (EoE) has increased
      rapidly. Most epidemiologic data were gathered in single-center studies over a
      short timeframe, possibly explaining the heterogeneous incidences. AIM: The aim
      of this study was to retrospectively estimate the Dutch nationwide incidence of
      EoE over the last 20 years. METHODS: The Dutch pathology registry (PALGA) was
      queried to identify pathology reports describing esophageal eosinophilia from
      1996 to 2016. Cases were eligible if EoE was confirmed by the pathologist. Using
      the annual Dutch population data, the incidence of EoE was calculated. KEY
      RESULTS: The search yielded 11 288 reports of which 5080 described esophageal
      eosinophilia. Eosinophilic esophagitis was diagnosed in 2161 patients, 1574 (73%)
      males and 365 (17%) children. The incidence increased from 0.01 (95% CI 0-0.02)
      in 1996 to 2.07 (95% CI 2.05-2.23) per 100 000 inhabitants in 2015. The incidence
      was higher in males than in females, 3.02 (95% CI 2.66-3.41) vs 1.14 (95% CI 0.93
      1.38), odds ratio (OR) 2.66 (95% CI 2.10-3.36) and higher in adults than in
      children, 2.23 (95% CI 1.99-2.49) vs 1.46 (95% CI 1.09-1.91), OR 1.78 (95% CI
      1.32-2.40). Incidence of EoE increased more than 200-fold, whereas endoscopy
      rates only tripled, from 30 in 1996 to 105 per 100 000 inhabitants in 2015. We
      observed no seasonal variation. CONCLUSIONS AND INFERENCES: In the last decades,
      the Dutch EoE incidence has increased tremendously and still continues to rise.
      This expansion is only partially driven by increased endoscopy rates.

PMID- 28745829
TI  - Nickel Diselenide Ultrathin Nanowires Decorated with Amorphous Nickel Oxide
      Nanoparticles for Enhanced Water Splitting Electrocatalysis.
AB  - Well-designed hybrid materials based on noble metal-free elements have great
      potential to generate hydrogen (H2 ) and oxygen (O2 ) sustainably via overall
      water splitting for developing practical energy-related technologies. Herein, an
      accessible method is presented to synthesize nickel diselenide (NiSe2 ) ultrathin
      nanowires decorated with amorphous nickel oxide nanoparticles (NiOx NPs) as
      multifunctional electrocatalysts (NSWANs) for hydrogen and oxygen evolution
      reaction (HER and OER). The NSWANs exhibit quite low HER and OER overpotentials
      of 174 and 295 mV, respectively, holding the current density of 20 mA cm-2 for 24
      h continuous operations in alkaline media. Meanwhile, a cell voltage of 1.547 V
      at the current density of 10 mA cm-2 for overall water splitting has been
      achieved by the NSWANs for the practical application, which could maintain
      fascinating activity of 20 mA cm-2 for 72 h without degradation. The decorated
      NiOx NPs not only prevent the NiSe2 from further oxidation but also expose
      requisite active sites for electrocatalytic process. It is believed that this
      study may provide a valuable strategy to design high-efficiency electrocatalysts
      and expand the applications of selenide-based materials.

PMID- 28745830
TI  - Reply.

PMID- 28745832
TI  - A survey of salmon gill poxvirus (SGPV) in wild salmonids in Norway.
AB  - In 2016, the Norwegian health monitoring programme for wild salmonids conducted a
      real-time PCR-based screening for salmon gill poxvirus (SGPV) in anadromous
      Arctic char (Salvelinus alpinus L.), anadromous and non-anadromous Atlantic
      salmon (Salmo salar L.) and trout (Salmo trutta L.). SGPV was widely distributed
      in wild Atlantic salmon returning from marine migration. In addition,
      characteristic gill lesions, including apoptosis, were detected in this species.
      A low amount of SGPV DNA, as indicated by high Ct-values, was detected in
      anadromous trout, but only in fish cohabiting with SGPV-positive salmon. SGPV was
      not detected in trout and salmon from non-anadromous water courses, and thus
      seems to be primarily linked to the marine environment. This could indicate that
      trout are not a natural host for the virus. SGPV was not detected in Arctic char
      but, due to a low sample size, these results are inconclusive. The use of
      freshwater from anadromous water sources may constitute a risk of introducing
      SGPV to aquaculture facilities. Moreover, SGPV-infected Atlantic salmon farms
      will hold considerable potential for virus propagation and spillback to wild
      populations. This interaction should therefore be further investigated.

PMID- 28745831
TI  - Osteopontin is linked with AKT, FoxO1, and myostatin in skeletal muscle cells.
AB  - INTRODUCTION: Osteopontin (OPN) polymorphisms are associated with muscle size and
      modify disease progression in Duchenne muscular dystrophy (DMD). We hypothesized
      that OPN may share a molecular network with myostatin (MSTN). METHODS: Studies
      were conducted in the golden retriever (GRMD) and mdx mouse models of DMD. Follow
      up in-vitro studies were employed in myogenic cells and the mdx mouse treated
      with recombinant mouse (rm) or human (Hu) OPN protein. RESULTS: OPN was increased
      and MSTN was decreased and levels correlated inversely in GRMD hypertrophied
      muscle. RM-OPN treatment led to induced AKT1 and FoxO1 phosphorylation, microRNA
      486 modulation, and decreased MSTN. An AKT1 inhibitor blocked these effects,
      whereas an RGD-mutant OPN protein and an RGDS blocking peptide showed similar
      effects to the AKT inhibitor. RMOPN induced myotube hypertrophy and minimal Feret
      diameter in mdx muscle. DISCUSSION: OPN may interact with AKT1/MSTN/FoxO1 to
      modify normal and dystrophic muscle. Muscle Nerve 56: 1119-1127, 2017.

PMID- 28745833
TI  - Full-layer mucosal histology in achalasia: Histological epithelial wave is
      characteristic in "pinstripe pattern"-positive achalasia.
AB  - BACKGROUND: Previously, the mucosal histology in achalasia has only been
      investigated using superficial biopsy or surgically resected esophageal specimens
      in end-stage cases. We investigated the histology of the full-layer mucosa in
      early and advanced achalasia. METHODS: Endoscopy was performed for the pinstripe
      pattern (PSP) (an early achalasia indicator) and dilation and thickening of the
      mucosa (advanced achalasia indicators). A mucosal entry site for peroral
      endoscopic myotomy was created using cap-fitted endoscopic mucosal resection to
      access the full-layer mucosa and the submucosa. KEY RESULTS: Mucosal histology
      was compared between 32 patients with achalasia and 15 controls. Histological
      esophagitis with findings of inflammatory cell infiltration and dilated
      intercellular spaces was observed more in patients with achalasia than in
      controls (87.5% vs 13.3%, P<.001; 84.4% vs 46.7%, P=.049). Muscularis mucosae
      (MM) atrophy and epithelial wave were only observed in achalasia (40.6% vs 0%,
      P=.005; 28.1% vs 0%, P=.043). Fibrosis was more common in achalasia, but without
      statistical significance (31.3% vs 20.0%, P=.503). In achalasia with endoscopic
      dilation and thickening of the mucosa, MM atrophy was observed histologically,
      and in cases involving endoscopic PSP, the histological epithelial wave was
      observed. CONCLUSIONS & INFERENCES: Histological findings of esophagitis were
      observed endoscopically even in early achalasia. Pinstripe pattern corresponds to
      the epithelial wave observed histologically in achalasia, whereas endoscopic
      findings in advanced achalasia correspond to MM atrophy. Appropriate management
      is necessary during early achalasia to prevent progression to advanced achalasia
      with more severe histological changes.

PMID- 28745834
TI  - What is your diagnosis? Blood film from a Black bear (Ursus americanus).

PMID- 28745835
TI  - Infectious pancreatic necrosis virus (IPNV) serotype Sp is prevalent in Turkish
      rainbow trout farms.
AB  - Infectious pancreatic necrosis virus (IPNV) is a common pathogen of rainbow trout
      (Oncorhynchus mykiss) in Turkey. We found that 455 of 1,676 sample pools tested
      were IPNV positive. Positive samples were found in all geographical regions where
      sampling was conducted. Sequence and phylogenetic analyses of VP2 from 30
      isolates representing all regions showed that the viruses were highly similar in
      sequence and grouped within Genogroup 5 (serotype Sp-A2). No correlations between
      sequences, sampling sites or geographical origins were identified. Although
      clinical disease was evident in several farms, analyses of the amino acid
      sequence of VP2 showed that all virus strains harboured the P217 T221 motif,
      assumed to be associated with low virulence. We conclude that IPNV is prevalent
      in Turkish rainbow trout farms and that the viruses are very homogenous and
      likely to be of European origin. Frequent exchange of eggs and live fish within
      the farming industry may explain the homogeneity of the IPNV.

PMID- 28745836
TI  - Effects of vesical and perfusion pressure on perfusate flow, and flow on vesical
      pressure, in the isolated perfused working pig bladder reveal a potential
      mechanism for the regulation of detrusor compliance.
AB  - AIMS: Although there is evidence that deficits in bladder blood flow negatively
      impact bladder function, the effects of vesical, and perfusion pressures on
      bladder perfusion (perfusate flow), and of perfusate flow on vesical pressure,
      remain poorly understood. The present study used the isolated perfused working
      pig bladder model to examine the relationships between blood flow, and vesical
      and perfusion pressures. METHODS: Vesical arteries of pig bladders obtained from
      a local slaughterhouse were cannulated and perfused with Krebs-Henseleit solution
      at different pressures, and with carbachol to cause bladder contraction. The
      urethra of each bladder was cannulated to permit filling (10 mL/min),
      isovolumetric contraction and emptying. A ureter was cannulated with a pressure
      sensor to monitor vesical pressure. RESULTS: When at rest (50 mL vesical volume),
      bladder vesical pressure was 8.06 +/- 1.5 mmHg and perfusate flow driven by a
      pressure gradient of 105 mmHg was 22.5 +/- 2 mL/min (58.9 +/- 7.8 mL/min-100 g).
      During filling, vesical pressure increased and flow decreased, but not
      necessarily in-parallel. Perfusate flow decreased transiently during
      isovolumetric contraction, and flow increased during emptying. A reduction in
      perfusion pressure from ~105 to ~40 mmHg reduced flow from ~70 to ~20 mL/min
      100g, and reduced flow correlated with reduced vesical pressure. CONCLUSION:
      Perfusate flow is dependent on bladder perfusion pressure, and not necessarily
      reciprocally dependent on vesical pressure. Vesical pressure is highly sensitive
      to the level of perfusate flow, which supports the hypothesis that vesical
      pressure is dependent on the level of detrusor smooth muscle contractile activity
      (tone), and that compliance is dependent on bladder perfusion.

PMID- 28745837
TI  - Prosecretory effect of loperamide in ileal and colonic mucosae of mice displaying
      high or low swim stress-induced analgesia associated with high and low endogenous
      opioid system activity.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is characterized by abdominal pain,
      bloating, and changes in bowel habit. The aim of this study was to characterize
      the effect of loperamide hydrochloride (LOP) and naloxone hydrochloride (NLX), an
      opioid agonist and antagonist, respectively, on electrolyte equilibrium in ileal
      and colonic mucosae and to estimate the possible influence of divergent activity
      of the endogenous opioid system (EOS) on IBS therapy. METHODS: Two mouse lines
      bidirectionally selected for high (HA) and low (LA) swim stress-induced analgesia
      associated with high and low EOS activity were used in this study. To assess the
      effect of LOP and NLX on HA/LA lines in vivo, we used the castor oil-induced
      diarrhea model. Changes in electrolyte equilibrium were determined on the basis
      of short-circuit current (DeltaIsc ) in isolated mouse ileum and colon exposed to
      LOP and NLX and stimulated by forskolin (FSK), veratridine (VER), and bethanechol
      (BET). KEY RESULTS: In vivo, we found that LOP significantly prolonged time to
      appearance of diarrhea in HA and LA lines. In vitro, LOP and NLX increased
      DeltaIsc in FSK- and VER-stimulated colonic tissue, respectively, in HA line. In
      the ileum, LOP increased DeltaIsc in FSK- and VER-stimulated tissue and decreased
      DeltaIsc in BET-stimulated tissues in HA line. CONCLUSIONS & INFERENCES:
      Individual differences in EOS activity may play a crucial role in the response to
      the IBS-D therapy, thus some patients may be at an increased risk of side effects
      such as constipation or diarrhea.

PMID- 28745838
TI  - First record of epizootic ulcerative syndrome from the Upper Congo catchment: An
      outbreak in the Bangweulu swamps, Zambia.
AB  - We report on the first outbreak of epizootic ulcerative syndrome (EUS) amongst
      wild fish populations in the Bangweulu swamps, an inland delta, in the north of
      Zambia during 2014. The area supports a large and diverse fish fauna related to,
      but distinct from, that of the Zambezi River system where EUS outbreaks have
      occurred since 2006. A sizeable artisanal fishery, based on extensive fish weirs,
      is sustained by the annual flooding of the swamps, and observations of the
      disease outbreak by fishermen were recorded. Signs typical of infection with
      Aphanomyces invadans were observed in a number of species. Clinical observations,
      histology and molecular diagnostic methods were used to confirm infection with A.
      invadans in two of the most commonly and severely affected species. Several
      features of the wetland may have contributed to the outbreak and the annual
      recurrence of the disease. Modes by which the disease may have been introduced
      into the swamps are discussed. The outbreak is of great significance as the
      Bangweulu swamps drain into the Congo River in neighbouring Democratic Republic
      of Congo, Africa's largest drainage system with an extensive and diverse fish
      fauna previously unaffected by EUS.

PMID- 28745839
TI  - Transcription factor Agseb1 affects development, osmotic stress response, and
      secondary metabolism in marine-derived Aspergillus glaucus.
AB  - Fungi possess sophisticated regulatory systems to respond to a vast array of
      environmental signals. Among these responsive networks, some genes play critical
      roles in the regulation of various cellular processes. Here, we identified a
      putative transcriptional factor Agseb1 in Aspergillus glaucus, a marine-derived
      filamentous fungus. Agseb1 encodes a protein with two C2 H2 zinc fingers at the C
      terminus, similar to the placement of these motifs in msn2/4 of Saccharomyces
      cerevisia, where they are positioned to allow binding to the CCCCT-box of stress
      specific genes. Agseb1 similarly plays a role in stress response and its deletion
      mutant exhibited decreased sensitivity to hyperosmotic stress (both sorbitol and
      salt). Agseb1 is also important for mediating morphological development, because
      DeltaAgseb1 formed compact colonies and abnormal hyphal cells with hyperbranching
      at new sites. Consistent with the observed defects in conidial yield and
      sporulation, transcription analysis of the central asexual development pathway
      revealed significant activity changes. Additionally, the strain lacking Agseb1
      exhibited a 43% decrease in aspergiolide A biosynthesis. Overall, Agseb1 has
      significant activity in different cellular pathways, the findings in this study
      may be generally applicable to the seb1 orthologs of other filamentous
      ascomycetes.

PMID- 28745840
TI  - Cyclic vomiting syndrome is a prevalent and under-recognized condition in the
      gastroenterology outpatient clinic.
AB  - BACKGROUND: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal
      disorder (FGID) characterized by intermittent episodes of nausea and vomiting.
      Our aim was to report its prevalence and associated features. METHODS: Data
      concerning demographics, symptoms, and psychiatric comorbidity were collected.
      Symptoms compatible with CVS were classified as per Rome III criteria. We
      recorded whether a diagnosis of CVS was considered in patients after negative
      investigation. We compared demographics and association with other FGIDs in
      patients with and without CVS. KEY RESULTS: 920 of 1002 patients provided data.
      Of the 920 patients, 112 (12.2%) had symptoms compatible with CVS. Thirteen
      (11.6%) of these had an organic cause for their symptoms, but 99 patients (88.4%)
      were deemed to have CVS (prevalence=10.8%). Organic causes for symptoms
      compatible with CVS included gastroparesis, large hiatus hernia, achalasia, and
      small bowel obstruction. Only 39.4% of patients with CVS were asked about
      vomiting symptoms at their initial consultation, and a diagnosis of CVS was
      considered in only four (4.0%) of the 99 patients. CVS was associated with
      younger age, tobacco smoking, never having married, psychiatric comorbidity, and
      presence of symptoms compatible with other FGIDs (P<=.01). CONCLUSIONS AND
      INFERENCES: Prevalence of CVS in this outpatient gastroenterology adult
      population was 10.8%. Identified associations included younger age, tobacco
      smoking, psychiatric comorbidity, and symptoms compatible with other FGIDs. The
      condition was considered as a possible diagnosis in <5% of patients who met the
      diagnostic criteria.

PMID- 28745841
TI  - Cervical artery dissection: early recognition and stroke prevention [digest].
AB  - Cervical artery dissections involve the carotid or vertebral arteries. Although
      the overall incidence is low, they remain a common cause of stroke in children,
      young adults, and trauma patients. Symptoms such as headache, neck pain, and
      dizziness are commonly seen in the emergency department, but may not be apparent
      in the obtunded trauma patient. A missed diagnosis of cervical artery dissection
      can result in devastating neurological sequelae, so emergency clinicians must act
      quickly to recognize this event and begin treatment as soon as possible while
      neurological consultation is obtained. This issue reviews the evidence in
      applying advanced screening criteria and choosing imaging and antithrombotic
      treatment strategies for patients with cervical artery dissections to reduce the
      occurrence of ischemic stroke. [Points & Pearls is a digest of Emergency Medicine
      Practice].

PMID- 28745842
TI  - Toxic alcohol ingestion: prompt recognition and management in the emergency
      department [digest].
AB  - Identifying patients with potential toxic alcohol exposure and initiating
      appropriate management is critical to avoid significant patient morbidity.
      Sources of toxic alcohol exposure include ethylene glycol, methanol, diethylene
      glycol, propylene glycol, and isopropanol. Treatment considerations include the
      antidotes fomepizole and ethanol, and hemodialysis for removal of the parent
      compound and its toxic metabolites. Additional interventions include adjunctive
      therapies that may improve acidosis and enhance clearance of the toxic alcohol or
      metabolites. This issue reviews common sources of alcohol exposure, basic
      mechanisms of toxicity, physical examination and laboratory findings that may
      guide rapid assessment and management, and indications for treatment. [Points &
      Pearls is a digest of Emergency Medicine Practice].

PMID- 28745843
TI  - Evidence-based management of potassium disorders in the emergency department
      [digest].
AB  - Hypokalemia and hyperkalemia are the most common electrolyte disorders managed in
      the emergency department. The diagnosis of these potentially life-threatening
      disorders is challenging due to the often vague symptomatology a patient may
      express, and treatment options may be based upon very little data due to the time
      it may take for laboratory values to return. This review examines the most
      current evidence with regard to the pathophysiology, diagnosis, and management of
      potassium disorders. In this review, classic paradigms, such as the use of sodium
      polystyrene and the routine measurement of serum magnesium, are tested, and an
      algorithm for the treatment of potassium disorders is discussed. [Points & Pearls
      is a digest of Emergency Medicine Practice].

PMID- 28745844
TI  - Emergency department management of priapism [digest].
AB  - Priapism is a genitourinary emergency that demands a thorough, time-sensitive
      evaluation. There are 3 types of priapism: ischemic, nonischemic, and recurrent
      ischemic priapism; ischemic priapism accounts for 95% of cases. Ischemic priapism
      must be treated within 4 to 6 hours to minimize morbidity, including impotence.
      The diagnosis of ischemic priapism relies heavily on the history and physical
      examination and may be facilitated by penile blood gas analysis and penile
      ultrasound. This issue reviews current evidence regarding emergency department
      treatment of ischemic priapism using a stepwise approach that begins with
      aspiration of cavernosal blood, cold saline irrigation, and penile injection with
      sympathomimetic agents. Evidence-based management and appropriate urologic follow
      up of nonischemic and recurrent ischemic priapism maximizes patient outcomes and
      resource utilization. [Points & Pearls is a digest of Emergency Medicine
      Practice].

PMID- 28745845
TI  - Sedative-hypnotic drug withdrawal syndrome: recognition and treatment [digest].
AB  - Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such
      as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma
      Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can
      cause tolerance, and abrupt cessation or a reduction in the quantity of the drug
      can precipitate a life-threatening withdrawal syndrome. Benzodiazepines,
      phenobarbital, propofol, and other GABA agonists or analogues can effectively
      control symptoms of withdrawal from GABAergic agents. Managing withdrawal
      symptoms requires a patient-specific approach that takes into account the
      physiologic pathways of the particular drugs used as well as the patient's age
      and comorbidities. Adjunctive therapies include alpha agonists, beta blockers,
      anticonvulsants, and antipsychotics. Newer pharmacological therapies offer
      promise in managing withdrawal symptoms. [Points & Pearls is a digest of
      Emergency Medicine Practice].

PMID- 28745846
TI  - Acute decompensated heart failure: new strategies for improving outcomes
      [digest].
AB  - Acute decompensated heart failure is a common emergency department presentation
      with significant associated morbidity and mortality. Heart failure accounts for
      more than 1 million hospitalizations annually, with a steadily increasing
      incidence as our population ages. This issue reviews recent literature regarding
      appropriate management of emergency department presentations of acute
      decompensated heart failure, with special attention to newer medication options.
      Emergency department management and appropriate interventions are discussed,
      along with critical decision-making points in resuscitation for both hypertensive
      and hypotensive patients. [Points & Pearls is a digest of Emergency Medicine
      Practice].

PMID- 28745847
TI  - Transient global amnesia: emergency department evaluation and management
      [digest].
AB  - Transient global amnesia is a clinically distinct syndrome characterized by the
      acute inability to form new memories. It can last up to 24 hours. The diagnosis
      is dependent on eliminating other more serious etiologies including toxic
      ingestions, acute strokes, complex partial seizures, and central nervous system
      infections. Transient global amnesia confers no known long-term risks; however,
      when abnormal signs or symptoms are present, they take precedence and guide the
      formulation of a differential diagnosis and investigation. In witnessed transient
      global amnesia with classic features, a minimalist approach is reasonable,
      avoiding overtesting, inappropriate medication, and medical interventions in
      favor of observation, ensuring patient safety, and reassuring patients and their
      families. This review provides a detailed framework for distinguishing transient
      global amnesia from its dangerous mimics and managing its course in the emergency
      department. [Points & Pearls is a digest of Emergency Medicine Practice].

PMID- 28745848
TI  - Optimizing survival outcomes for adult patients with nontraumatic cardiac arrest
      [digest].
AB  - Patient survival after cardiac arrest can be improved significantly with prompt
      and effective resuscitative care. This systematic review analyzes the basic life
      support factors that improve survival outcome, including chest compression
      technique and rapid defibrillation of shockable rhythms. For patients who are
      successfully resuscitated, comprehensive postresuscitation care is essential.
      Targeted temperature management is recommended for all patients who remain
      comatose, in addition to careful monitoring of oxygenation, hemodynamics, and
      cardiac rhythm. Management of cardiac arrest in circumstances such as pregnancy,
      pulmonary embolism, opioid overdose and other toxicologic causes, hypothermia,
      and coronary ischemia are also reviewed. [Points & Pearls is a digest of
      Emergency Medicine Practice].

PMID- 28745849
TI  - Pelvic inflammatory disease: diagnosis and treatment in the emergency department
      [digest].
AB  - Pelvic inflammatory disease is a common disease that is associated with
      significant complications including infertility, chronic pelvic pain, ruptured
      tubo-ovarian abscess, and ectopic pregnancy. The diagnosis may be delayed when
      the presentation has nonspecific signs and symptoms. Even when it is properly
      identified, pelvic inflammatory disease is often treated suboptimally. This
      review provides evidence-based recommendations for the diagnosis, treatment,
      disposition, and follow-up of patients with pelvic inflammatory disease.
      Arranging follow-up of patients within 48 to 72 hours and providing clear patient
      education are fundamental to ensuring good patient outcomes. Emerging issues,
      including new pathogens and evolving resistance patterns among pelvic
      inflammatory disease pathogens are reviewed. [Points & Pearls is a digest of
      Emergency Medicine Practice].

PMID- 28745850
TI  - Noninvasive ventilation for patients in acute respiratory distress: an update
      [digest].
AB  - Over the last 20 years, noninvasive ventilation (NIV) strategies have been used
      with increasing frequency. The ease of use of NIV makes it applicable to patients
      presenting in a variety of types of respiratory distress. In this review, the
      physiology of positive pressure ventilation is discussed, including indications,
      contraindications, and options for mask type and fit. Characteristics of patients
      who are most likely to benefit from NIV are reviewed, including those in
      respiratory distress from chronic obstructive pulmonary disease exacerbation and
      cardiogenic pulmonary edema. The literature for other respiratory pathologies
      where NIV may be used, such as in asthma exacerbation, pediatric patients, and
      community-acquired pneumonia, is also reviewed. Controversies and potential
      future applications of NIV are presented. [Points & Pearls is a digest of
      Emergency Medicine Practice].

PMID- 28745851
TI  - Maxillofacial trauma: managing potentially dangerous and disfiguring complex
      injuries [digest].
AB  - Patients with maxillofacial trauma require a careful evaluation due to the
      anatomical proximity of the maxillofacial region to the head and neck. Facial
      injuries can range from soft-tissue lacerations and nondisplaced nasal fractures
      to severe, complex fractures, eye injuries, and possible brain injury. Though the
      Advanced Trauma Life Support (ATLS) guidelines provide a framework for the
      management of trauma patients, they do not provide a detailed reference for many
      subtle or complex facial injuries. This issue adds a more comprehensive and
      systematic approach to the secondary survey of the maxillofacial area and
      emergency department management of injuries to the face. In addition to an
      overall review of maxillofacial trauma pathophysiology, associated injuries, and
      physical examination, this review will also discuss relevant imaging, treatment,
      and disposition plans. [Points & Pearls is a digest of Emergency Medicine
      Practice].

PMID- 28745852
TI  - Vascular access in pediatric patients in the emergency department: types of
      access, indications, and complications [digest].
AB  - Vascular access is a potentially life-saving procedure that is a mainstay of
      emergency medicine practice. There are a number of challenges associated with
      obtaining and maintaining vascular access, and the choice of the route of access
      and equipment used will depend on patient- and provider-specific factors. In this
      issue, the indications and complications of peripheral intravenous access,
      intraosseous access, and central venous access are reviewed. Timely and effective
      assessment and management of difficult-access patients, pain control techniques
      that can assist vascular access, and contraindications to each type of vascular
      access are also discussed. [Points & Pearls is a digest of Pediatric Emergency
      Medicine Practice].

PMID- 28745853
TI  - Pneumothorax in pediatric patients: management strategies to improve patient
      outcomes [digest].
AB  - The clinical presentation of pneumothorax is highly variable. Spontaneous
      pneumothoraces may present with subtle symptoms when a small air leak is present,
      but can progress to hemodynamic instability in the setting of tension physiology.
      The etiologies are broad and the severity can vary greatly. A trauma patient with
      a pneumothorax may also have the added complexity of other potentially life
      threatening injuries. While there is a wealth of evidence-based guidelines for
      the management of pneumothoraces in the adult literature, the approach to
      pediatric patients is largely extrapolated from that literature without a
      significant evidence base. In this issue, aspects of the history and physical
      examination, the use of various diagnostic imaging modalities, and the range of
      interventions available to the emergency clinician are discussed. [Points &
      Pearls is a digest of Pediatric Emergency Medicine Practice].

PMID- 28745854
TI  - Vaccine-preventable diseases in pediatric patients: a review of measles, mumps,
      rubella, and varicella [digest].
AB  - Vaccine-preventable diseases such as measles, mumps, rubella, and varicella
      continue to plague children and adults worldwide. Although public health programs
      have helped decrease the prevalence and sequelae of these diseases, outbreaks
      still occur. To limit the spread of these diseases, emergency clinicians must be
      able to readily identify the characteristic presentations of the rashes
      associated with measles, rubella, and varicella, as well as the common presenting
      features associated with mumps. Diagnostic laboratory studies are not usually
      necessary, as a complete history and physical examination usually lead to an
      accurate diagnosis. Treatment for these vaccine-preventable diseases usually
      consists of supportive care, but, in some cases, severe complications and death
      may occur. This issue provides a review of the clinical features, differential
      diagnoses, potential complications, and treatment options for measles, mumps,
      rubella, and varicella. [Points & Pearls is a digest of Pediatric Emergency
      Medicine Practice].

PMID- 28745855
TI  - Managing acute complications of sickle cell disease in pediatric patients
      [digest].
AB  - Sickle cell disease is a chronic hematologic disease with a variety of acute, and
      often recurring, complications. Vaso-occlusive crisis, a unique but common
      presentation in sickle cell disease, can be challenging to manage. Acute chest
      syndrome is the leading cause of death in patients with sickle cell disease,
      occurring in more than half of patients who are hospitalized with a vaso
      occlusive crisis. Uncommon diagnoses in children, such as stroke, priapism, and
      transient red cell aplasia, occur more frequently in patients with sickle cell
      disease and necessitate a degree of familiarity with the disease process and its
      management. Patients with sickle cell trait generally have a benign course, but
      are also subject to serious complications. This issue provides a current review
      of evidence-based management of the most common acute complications of sickle
      cell disease seen in pediatric patients in the emergency department. [Points &
      Pearls is a digest of Pediatric Emergency Medicine Practice].

PMID- 28745856
TI  - Severe traumatic brain injury in children: an evidence-based review of emergency
      department management [digest].
AB  - More than 1.7 million traumatic brain injuries occur in adults and children each
      year in the United States, with approximately 30% occurring in children aged < 14
      years. Traumatic brain injury is a significant cause of morbidity and mortality
      in pediatric trauma patients. Early identification and management of severe
      traumatic brain injury is crucial in decreasing the risk of secondary brain
      injury and optimizing outcome. The main focus for early management of severe
      traumatic brain injury is to mitigate and prevent secondary injury, specifically
      by avoiding hypotension and hypoxia, which have been associated with poorer
      outcomes. This issue discusses methods to maintain adequate oxygenation, maximize
      management of intracranial hypertension, and optimize blood pressure in the
      emergency department to improve neurologic outcomes following pediatric severe
      traumatic brain injury. [Points & Pearls is a digest of Pediatric Emergency
      Medicine Practice].

PMID- 28745857
TI  - Altered level of consciousness: evidence-based management in the emergency
      department [digest].
AB  - A child who presents to the emergency department with an altered level of
      consciousness can be clinically unstable and can pose a great diagnostic
      challenge. The emergency clinician must quickly develop a wide differential of
      possible etiologies in order to administer potentially life-saving medications or
      interventions. The history, physical examination, and appropriate diagnostic
      tests can aid greatly in rapidly narrowing the differential diagnosis. Once
      initial stabilization, workup, and first-line interventions are completed, most
      patients who present with unresolved or unidentified altered level of
      consciousness should be admitted for further evaluation and close monitoring.
      This issue provides a review of the etiologies of altered level of consciousness
      as well as guidance for the management and disposition of patients with this
      condition. [Points & Pearls is a digest of Pediatric Emergency Medicine
      Practice].

PMID- 28745858
TI  - Correction to Orientation Control of Interfacial Magnetism at
      La0.67Sr0.33MnO3/SrTiO3 Interfaces.

PMID- 28745859
TI  - Quantitative Effects of O-Linked Glycans on Protein Folding.
AB  - Protein O-glycosylation is a diverse, common, and important post-translational
      modification of both proteins inside the cell and those that are secreted or
      membrane-bound. Much work has shown that O-glycosylation can alter the structure,
      function, and physical properties of the proteins to which it is attached. One
      gap remaining in our understanding of O-glycoproteins is how O-glycans might
      affect the folding of proteins. Here, we took advantage of synthetic, homogeneous
      O-glycopeptides to show that certain glycosylation patterns have an intrinsic
      effect, independent of any cellular folding machinery, on the folding pathway of
      a model O-glycoprotein, a carbohydrate binding module (CBM) derived from the
      Trichoderma reesei cellulase TrCel7A. The strongest effect, a 6-fold increase in
      overall folding rate, was observed when a single O-mannose was the glycan, and
      the glycosylation site was near the N-terminus of the peptide sequence. We were
      also able to show that glycosylation patterns affected the kinetics of each step
      in unique ways, which may help to explain the observations made here. This work
      is a first step toward quantitative understanding of how O-glycosylation might
      control, through intrinsic means, the folding of O-glycoproteins. Such an
      understanding is expected to facilitate future investigations into the effects of
      glycosylation on more biological processes related to protein folding.

PMID- 28745860
TI  - Bioluminescent Probes for Imaging Biology beyond the Culture Dish.
AB  - Bioluminescence with luciferase-luciferin pairs is an attractive method for
      surveying cells in live tissues and whole organisms. Recent advances in luciferin
      chemistry and luciferase engineering are further expanding the scope of the
      technology. It is now possible to spy on cells in a variety of deep tissues and
      visualize multicellular interactions, feats that are enabling new questions to be
      asked and new ideas to be explored. This perspective piece highlights recent
      successes in bioluminescent probe development and their applications to imaging
      in live cells, tissues, and animals.

PMID- 28745861
TI  - Mass Spectrometric Imaging of Ceramide Biomarkers Tracks Therapeutic Response in
      Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) is a serious public health problem and the leading
      cause of death in children and young adults. It also contributes to a substantial
      number of cases of permanent disability. As lipids make up over 50% of the brain
      mass and play a key role in both membrane structure and cell signaling, their
      profile is of particular interest. In this study, we show that advanced mass
      spectrometry imaging (MSI) has sufficient technical accuracy and reproducibility
      to demonstrate the anatomical distribution of 50 MUm diameter microdomains that
      show changes in brain ceramide levels in a rat model of controlled cortical
      impact (CCI) 3 days post injury with and without treatment. Adult male Sprague
      Dawley rats received one strike and were euthanized 3 days post trauma. Brain MS
      images showed increase in ceramides in CCI animals compared to control as well as
      significant reduction in ceramides in CCI treated animals, demonstrating
      therapeutic effect of a peptide agonist. The data also suggests the presence of
      diffuse changes outside of the injured area. These results shed light on the
      extent of biochemical and structural changes in the brain after traumatic brain
      injury and could help to evaluate the efficacy of treatments.

PMID- 28745862
TI  - GlcNAc Conjugated Atorvastatin with Enhanced Water Solubility and Cellular
      Internalization.
AB  - Targeting ligands facilitate cell specific drug delivery and improve
      pharmaceutical properties. Herein, we designed two ligand drug conjugates by
      conjugating GlcNAc (N-acetylglucosamine) with atorvastatin. These two conjugates,
      termed G-AT and G-K-AT, exhibited enhanced water solubility and cellular uptake.
      Moreover, both G-AT and G-K-AT were able to release atorvastatin and consequently
      achieve significant inhibition against 3-hydroxy-3-methyl-glutaryl-coenzyme A
      (HMG-CoA) reductase.

PMID- 28745863
TI  - Sandwich-Type NbS2@S@I-Doped Graphene for High-Sulfur-Loaded, Ultrahigh-Rate, and
      Long-Life Lithium-Sulfur Batteries.
AB  - Lithium-sulfur batteries practically suffer from short cycling life, low sulfur
      utilization, and safety concerns, particularly at ultrahigh rates and high sulfur
      loading. To address these problems, we have designed and synthesized a ternary
      NbS2@S@IG composite consisting of sandwich-type NbS2@S enveloped by iodine-doped
      graphene (IG). The sandwich-type structure provides an interconnected conductive
      network and plane-to-point intimate contact between layered NbS2 (or IG) and
      sulfur particles, enabling sulfur species to be efficiently entrapped and
      utilized at ultrahigh rates, while the structural integrity is well maintained.
      NbS2@S@IG exhibits prominent high-power charge/discharge performances. Reversible
      capacities of 195, 107, and 74 mA h g-1 (1.05 mg cm-2) have been achieved after
      2000 cycles at ultrahigh rates of 20, 30, and 40 C, respectively, and the
      corresponding average decay rates per cycle are 0.022%, 0.031% and 0.033%,
      respectively. When the area sulfur loading is increased to 3.25 mg cm-2, the
      electrode still maintains a high discharge capacity of 405 mAh g-1 after 600
      cycles at 1 C. Three half-cells in series assembled with NbS2@S@IG can drive 60
      indicators of LED modules after only 18 s of charging. The instantaneous current
      and power of the device reach 196.9 A g-1 and 1369.7 W g-1, respectively.

PMID- 28745865
TI  - Electroactive Biofilms for Sensing: Reflections and Perspectives.
AB  - Microbial electrochemistry has from the onset been recognized for its sensing
      potential due to the microbial ability to enhance signals through metabolic
      cascades, its relative selectivity toward substrates, and the higher stability
      conferred by the microbial ability to self-replicate. The greatest challenge has
      been to achieve stable and efficient transduction between a microorganism and an
      electrode surface. Over the past decades, a new kind of microbial architecture
      has been observed to spontaneously develop on polarized electrodes: the
      electroactive biofilm (EAB). The EAB conducts electrons over long distances and
      performs quasi-reversible electron transfer on conventional electrode surfaces.
      It also possesses self-regenerative properties. In only a few years, EABs have
      inspired considerable research interest for use as biosensors for environmental
      or bioprocess monitoring. Multiple challenges still need to be overcome before
      implementation at larger scale of this new kind of biosensors can be realized.
      This perspective first introduces the specific characteristics of the EAB with
      respect to other electrochemical biosensors. It summarizes the sensing
      applications currently proposed for EABs, stresses their limitations, and
      suggests strategies toward potential solutions. Conceptual prospects to engineer
      EABs for sensing purposes are also discussed.

PMID- 28745864
TI  - Voltage Imaging: Pitfalls and Potential.
AB  - Optical methods for interrogating membrane potential changes in neurons promise
      to revolutionize our ability to dissect the activity of individual cells embedded
      in neural circuits underlying behavior and sensation. A number of voltage imaging
      strategies have emerged in the past few years. This Perspective discusses
      developments in both small-molecule and genetically encoded fluorescent
      indicators of membrane potential. We survey recent advances in small-molecule
      fluorescent indicators that rely on photoinduced electron transfer to sense
      voltage as well as refinements of voltage-sensitive fluorescent proteins and new
      opsin-based strategies for monitoring voltage changes. We compare the
      requirements of fluorescent voltage indicators to those for more canonical Ca2+
      sensing as a way to illuminate the particular challenges associated with voltage
      imaging.

PMID- 28745866
TI  - Water-Dispersed Hydrophobic Au Nanocrystal Assemblies with a Plasmon Fingerprint.
AB  - Hydrophobic Au nanocrystal assemblies (both ordered and amorphous) were dispersed
      in aqueous solution via the assistance of lipid vesicles. The intertwine between
      vesicles and Au assemblies was made possible through a careful selection of the
      length of alkyl chains on Au nanocrystals. Extinction spectra of Au assemblies
      showed two peaks that were assigned to a scattering mode that red-shifted with
      increasing the assembly size and an absorption mode associated with localized
      surface plasmon that was independent of their size. This plasmon fingerprint
      could be used as a probe for investigating the optical properties of such
      assemblies. Our water-soluble assemblies enable exploring a variety of potential
      applications including solar energy and biomedicine.

PMID- 28745867
TI  - Development of Chemical and Metabolite Sensors for Rhodococcus opacus PD630.
AB  - Rhodococcus opacus PD630 is a nonmodel, Gram-positive bacterium that possesses
      desirable traits for biomass conversion, including consumption capabilities for
      lignocellulose-based sugars and toxic lignin-derived aromatic compounds,
      significant triacylglycerol accumulation, relatively rapid growth rate, and
      genetic tractability. However, few genetic elements have been directly
      characterized in R. opacus, limiting its application for lignocellulose
      bioconversion. Here, we report the characterization and development of genetic
      tools for tunable gene expression in R. opacus, including: (1) six fluorescent
      reporters for quantifying promoter output, (2) three chemically inducible
      promoters for variable gene expression, and (3) two classes of metabolite sensors
      derived from native R. opacus promoters that detect nitrogen levels or aromatic
      compounds. Using these tools, we also provide insights into native aromatic
      consumption pathways in R. opacus. Overall, this work expands the ability to
      control and characterize gene expression in R. opacus for future lignocellulose
      based fuel and chemical production.

PMID- 28745868
TI  - Bioinspired Design of Three-Dimensional Ordered Tribrachia-Post Arrays with Re
      entrant Geometry for Omniphobic and Slippery Surfaces.
AB  - Hydro- and oleophobic (namely, omniphobic) coatings or surfaces have many
      important applications, but tremendous challenges in fabrication aspects still
      remain. Herein, we report a bioinspired design and nanofabrication of three
      dimensional (3D) tribrachia-post arrays with re-entrant geometry (3D TPARG) for
      superhydrophobic and oleophobic polymer films or surfaces. By simply controlling
      the temperatures and time to treat silica colloidal templates, we can readily
      fabricate 3D ordered polymer arrays of tribrachia-posts or hexagonal tribrachia
      posts with re-entrant geometries that resemble the skin of a springtail insect
      after the template is removed. These polymer surfaces exhibit excellent and self
      healing superhydrophobicity and oleophobicity even against temperature, acids,
      alkalis, and mechanical damage. Moreover, their liquid-infused nanostructured
      surfaces still display very good liquid-sliding ability for water and oils. Our
      3D TPARG design strategy may help the development of omniphobic polymer coatings
      or surfaces for practical applications in self-cleaning surfaces, liquid
      transport, antifouling materials, and many other important fields.

PMID- 28745869
TI  - High-Resolution Imaging and Multiparametric Characterization of Native Membranes
      by Combining Confocal Microscopy and an Atomic Force Microscopy-Based Toolbox.
AB  - To understand how membrane proteins function requires characterizing their
      structure, assembly, and inter- and intramolecular interactions in
      physiologically relevant conditions. Conventionally, such multiparametric insight
      is revealed by applying different biophysical methods. Here we introduce the
      combination of confocal microscopy, force-distance curve-based (FD-based) atomic
      force microscopy (AFM), and single-molecule force spectroscopy (SMFS) for the
      identification of native membranes and the subsequent multiparametric analysis of
      their membrane proteins. As a well-studied model system, we use native purple
      membrane from Halobacterium salinarum, whose membrane protein bacteriorhodopsin
      was His-tagged to bind nitrilotriacetate (NTA) ligands. First, by confocal
      microscopy we localize the extracellular and cytoplasmic surfaces of purple
      membrane. Then, we apply AFM to image single bacteriorhodopsins approaching sub
      nanometer resolution. Afterwards, the binding of NTA ligands to
      bacteriorhodopsins is localized and quantified by FD-based AFM. Finally, we apply
      AFM-based SMFS to characterize the (un)folding of the membrane protein and to
      structurally map inter- and intramolecular interactions. The multimethodological
      approach is generally applicable to characterize biological membranes and
      membrane proteins at physiologically relevant conditions.

PMID- 28745870
TI  - Anti-UV Radiation Textiles Designed by Embracing with Nano-MIL (Ti, In)-Metal
      Organic Framework.
AB  - Protective textiles against harmful solar radiation are quite important materials
      for outdoor workers to secure their skin from several diseases. Current report
      focuses on production of anti-ultraviolet radiation (UVR) textiles by
      incorporation of nano-metal-organic frameworks (n-MOFs). Two different MIL-MOFs,
      namely, MIL-68(In)-NH2 and MIL-125(Ti)-NH2, were immediately formed inside
      natural textiles (cotton and silk) matrix in nano size using quite simple and one
      pot process. The formation of n-MIL-MOFs inside textiles were confirmed by using
      electron microscope and X-ray diffraction. Different size and morphology were
      seen depending on textile type reflecting the textiles' chemical composition role
      in the nature of prepared MIL-MOFs. For MIL-68(In)-NH2, particles with size
      distribution of 70.6-44.5 nm in cotton and 81.3-52.2 nm in silk were detected,
      while crystalline disc of MIL-125(Ti)-NH2 was clearly seen inside textiles. The
      natural textiles exhibited full UVR blocking after modification, and the UV
      protection factor (UPF) was linearly proportional with MIL-MOFs and metal
      contents. Whatever metal type, direct incorporation of MIL-MOF contents greater
      than or equal to 10.4 g/kg was sufficient to attain excellent UV blocking
      property. Although 38.5-41.0% of MIL-MOFs was lost during five washings, the
      washed samples showed very good blocking rate (UPF = 26.7-36.2) supporting good
      laundering durability.

PMID- 28745871
TI  - Local Electric Field Facilitates High-Performance Li-Ion Batteries.
AB  - By scrutinizing the energy storage process in Li-ion batteries, tuning Li-ion
      migration behavior by atomic level tailoring will unlock great potential for
      pursuing higher electrochemical performance. Vacancy, which can effectively
      modulate the electrical ordering on the nanoscale, even in tiny concentrations,
      will provide tempting opportunities for manipulating Li-ion migratory behavior.
      Herein, taking CuGeO3 as a model, oxygen vacancies obtained by reducing the
      thickness dimension down to the atomic scale are introduced in this work. As the
      Li-ion storage progresses, the imbalanced charge distribution emerging around the
      oxygen vacancies could induce a local built-in electric field, which will
      accelerate the ions' migration rate by Coulomb forces and thus have benefits for
      high-rate performance. Furthermore, the thus-obtained CuGeO3 ultrathin nanosheets
      (CGOUNs)/graphene van der Waals heterojunctions are used as anodes in Li-ion
      batteries, which deliver a reversible specific capacity of 1295 mAh g-1 at 100 mA
      g-1, with improved rate capability and cycling performance compared to their bulk
      counterpart. Our findings build a clear connection between the
      atomic/defect/electronic structure and intrinsic properties for designing high
      efficiency electrode materials.

PMID- 28745872
TI  - Investigating Limiting Factors in Stretchable All-Carbon Transistors for Reliable
      Stretchable Electronics.
AB  - Stretchable form factors enable electronic devices to conform to irregular 3D
      structures, including soft and moving entities. Intrinsically stretchable devices
      have potential advantages of high surface coverage of active devices, improved
      durability, and reduced processing costs. This work describes intrinsically
      stretchable transistors composed of single-walled carbon nanotube (SWNT)
      electrodes and semiconductors and a dielectric that consists of a nonpolar
      elastomer. The use of a nonpolar elastomer dielectric enabled hysteresis-free
      device characteristics. Compared to devices on SiO2 dielectrics, stretchable
      devices with nonpolar dielectrics showed lower mobility in ambient conditions
      because of the absence of doping from water. The effect of a SWNT band gap on
      device characteristics was investigated by using different SWNT sources as the
      semiconductor. Large-band-gap SWNTs exhibited trap-limited behavior caused by the
      low capacitance of the dielectric. In contrast, high-current devices based on
      SWNTs with smaller band gaps were more limited by contact resistance. Of the
      tested SWNT sources, SWNTs with a maximum diameter of 1.5 nm performed the best,
      with a mobility of 15.4 cm2/Vs and an on/off ratio >103 for stretchable
      transistors. Large-band-gap devices showed increased sensitivity to strain
      because of a pronounced dependence on the dielectric thickness, whereas contact
      limited devices showed substantially less strain dependence.

PMID- 28745873
TI  - Physiological Concentrations of Ascorbate Cannot Prevent the Potentially Damaging
      Reactions of Protein Radicals in Humans.
AB  - The principal initial biological targets of free radicals formed under conditions
      of oxidative stress are the proteins. The most common products of the interaction
      are carbon-centered alkyl radicals which react rapidly with oxygen to form
      peroxyl radicals and hydroperoxides. All these species are reactive, capable of
      propagating the free radical damage to enzymes, nucleic acids, lipids, and
      endogenous antioxidants, leading finally to the pathologies associated with
      oxidative stress. The best chance of preventing this chain of damage is in early
      repair of the protein radicals by antioxidants. Estimate of the effectiveness of
      the physiologically significant antioxidants requires knowledge of the
      antioxidant tissue concentrations and rate constants of their reaction with
      protein radicals. Previous studies by pulse radiolysis have shown that only
      ascorbate can repair the Trp and Tyr protein radicals before they form peroxyl
      radicals under physiological concentrations of oxygen. We have now extended this
      work to other protein C-centered radicals generated by hydroxyl radicals because
      these and many other free radicals formed under oxidative stress can produce
      secondary radicals on virtually any amino acid residue. Pulse radiolysis
      identified two classes of rate constants for reactions of protein radicals with
      ascorbate, a faster one in the range (9-60) * 107 M-1 s-1 and a slow one with a
      range of (0.5-2) * 107 M-1 s-1. These results show that ascorbate can prevent
      further reactions of protein radicals only in the few human tissues where its
      concentration exceeds about 2.5 mM.

PMID- 28745874
TI  - New Molecular Design Concurrently Providing Superior Pure Blue, Thermally
      Activated Delayed Fluorescence and Optical Out-Coupling Efficiencies.
AB  - Simultaneous enhancement of out-coupling efficiency, internal quantum efficiency,
      and color purity in thermally activated delayed fluorescence (TADF) emitters is
      highly desired for the practical application of these materials. We designed and
      synthesized two isomeric TADF emitters, 2DPyM-mDTC and 3DPyM-pDTC, based on
      di(pyridinyl)methanone (DPyM) cores as the new electron-accepting units and
      di(tert-butyl)carbazole (DTC) as the electron-donating units. 3DPyM-pDTC, which
      is structurally nearly planar with a very small DeltaEST, shows higher color
      purity, horizontal ratio, and quantum yield than 2DPyM-mDTC, which has a more
      flexible structure. An electroluminescence device based on 3DPyM-pDTC as the
      dopant emitter can reach an extremely high external quantum efficiency of 31.9%
      with a pure blue emission. This work also demonstrates a way to design materials
      with a high portion of horizontal molecular orientation to realize a highly
      efficient pure-blue device based on TADF emitters.

PMID- 28745875
TI  - Ruthenium-Catalyzed Site-Selective Intramolecular Silylation of Primary C-H Bonds
      for Synthesis of Sila-Heterocycles.
AB  - Incorporating the silicon element into bioactive organic molecules has received
      increasing attention in medicinal chemistry. Moreover, organosilanes are valuable
      synthetic intermediates for fine chemicals and materials. Transition metal
      catalyzed C-H silylation has become an important strategy for C-Si bond
      formations. However, despite the great advances in aromatic C(sp2)-H bond
      silylations, catalytic methods for aliphatic C(sp3)-H bond silylations are
      relatively rare. Here we report a pincer ruthenium catalyst for intramolecular
      silylations of various primary C(sp3)-H bonds adjacent to heteroatoms (O, N, Si,
      Ge), including the first intramolecular silylations of C-H bonds alpha to O, N,
      and Ge. This method provides a general, synthetically efficient approach to novel
      classes of Si-containing five-membered [1,3]-sila-heterocycles, including
      oxasilolanes, azasilolanes, disila-heterocycles, and germasilolane. The trend in
      the reactivity of five classes of C(sp3)-H bonds toward the Ru-catalyzed
      silylation is elucidated. Mechanistic studies indicate that the rate-determining
      step is the C-H bond cleavage involving a ruthenium silyl complex as the key
      intermediate, while a eta2-silene ruthenium hydride species is determined to be
      an off-cycle intermediate.

PMID- 28745876
TI  - Ionic Liquids as Tool to Improve Enzymatic Organic Synthesis.
AB  - Ionic liquids (ILs) have now been acknowledged as reaction media for
      biotransformations. The first three examples were reported in this field in 2000,
      and since then, numerous applications have been reported for biocatalytic
      reactions using ILs. Two topics using ILs for enzymatic reactions have been
      reviewed from the standpoint of biocatalyst mediating organic synthesis; the
      first is "Biocatalysis in Ionic Liquids" which includes various types of
      biocatalytic reactions in ILs (section 2): (1) recent examples of lipase-mediated
      reactions using ILs as reaction media for biodiesel oil production and for sugar
      ester production, (2) oxidase-catalyzed reactions in ILs, (3) laccase-catalyzed
      reactions, (4) peroxidase-catalyzed reactions, (4) cytochrome-mediated reactions,
      (5) microbe-mediated hydrations, (6) protease-catalyzed reactions, (8) whole cell
      mediated asymmetric reduction of ketones, (10) acylase-catalyzed reactions, (11)
      glycosylation or cellulase-mediated hydrolysis of polysaccharides, (12)
      hydroxynitrile lyase-catalyzed reaction, (13) fluorinase or haloalkane
      dehydrogenase-catalyzed reaction, (14) luciferase-catalyzed reactions, and (15)
      biocatalytic promiscuity of enzymatic reactions for organic synthesis using ILs.
      The second is "Enzymes Activated by Ionic Liquids for Organic Synthesis",
      particularly describing the finding story of activation of lipases by the coating
      with a PEG-substituted IL (section 3). The author's opinion toward "Future
      Perspectives of Using ILs for Enzymatic Reactions" has also been discussed in
      section 4.

PMID- 28745877
TI  - Boron "Doped" Polyacetylenes.
AB  - We report the synthesis and characterization of a novel series of main-chain
      boron-containing conjugated polymers (CPs), boron "doped" polyacetylenes (BPAs),
      which represent the first examples of main-chain boron-containing CPs without
      aromatic moieties within the polymer backbone, potentially enhancing electronic
      delocalization along the main-chain. These polymers are characterized by NMR,
      absorption and emission spectroscopy, cyclic voltammetry, theoretical
      calculation, and fluoride titration experiments, providing detailed understanding
      of the effects from different cross-conjugated side-chains on the physical and
      electronic properties of this new class of boron-containing polymers.

PMID- 28745878
TI  - Electronic Transport in Bilayer MoS2 Encapsulated in HfO2.
AB  - The exact nature of the interface between a two-dimensional crystal and its
      environment can have a significant impact on the electronic transport within the
      crystal, and can place fundamental limitations on transistor performance and long
      term functionality. Two-dimensional transition-metal dichalcogenides are a new
      class of transistor channel material with electronic properties that can be
      tailored through dielectric engineering of the material/environmental interface.
      Here, we report electrical transport measurements carried out in the insulating
      regime of bilayer molybdenum disulfide, which has been encapsulated within a high
      kappa hafnium oxide dielectric. Temperature- and carrier-density-dependent
      measurements show that for T < 130 K the transport is governed by resonant
      tunneling, and at T = 4.2 K the tunneling peak lineshape is well-fitted by a
      Lorentzian with an amplitude less than e2/h. Estimates of tunneling time give tau
      ~ 1.2 ps corresponding to a frequency f ~ 0.84 THz. The tunneling processes are
      observable up to T ~ 190 K (more than a factor of 6 higher than that previously
      reported for MoS2 on SiO2) despite the onset of variable range hopping at T ~ 130
      K, demonstrating the coexistence of the two transport processes within the same
      temperature range. At constant temperature, varying the Fermi energy allows
      experimental access to each transport process. The results are interpreted in
      terms of an increase in charge carrier screening length and a decrease in
      electron-phonon coupling induced by the hafnium oxide. Our results represent the
      first demonstration of the intermediate tunneling-hopping transport regime in a
      two-dimensional material. The results suggest that interface engineering may be a
      macroscopic tool for controlling quantum transport within such materials as well
      as for increasing the operating temperatures for resonant-tunneling devices
      derived from such materials, with applications in high-frequency electronics and
      logic devices.

PMID- 28745879
TI  - Plasma-Induced Degradation of Quercetin Associated with the Enhancement of
      Biological Activities.
AB  - Nonthermal plasma is a promising technology to improve the safety and to extend
      the shelf-life of various minimally processed foods. However, research on plasma
      induced systemic degradation related to changes in chemical structure and
      biological activity is still very limited. In this study, the enhancement of
      biological activity and the mechanism of degradation of the most common type of
      flavonol, quercetin, induced by a dielectric barrier discharge (DBD) plasma were
      investigated. Quercetin is dissolved in methanol and exposed to nonthermal DBD
      plasma for 5, 10, 20, and 30 min. The quercetin treated with the plasma for 20
      min showed rapidly increased alpha-glucosidase inhibitory and radical scavenging
      activities compared to those of parent quercetin. The structures of the
      degradation products 1-3 from the quercetin treated with the plasma for 20 min
      were isolated and characterized by interpretation of their spectroscopic data.
      Among the generated products, (+/-)-alphitonin (1) exhibited significantly
      improved antidiabetic and antioxidant properties compared to those of the parent
      quercetin. The antidiabetic and antioxidant properties were measured by alpha
      glucosidase inhibition and 1,1-diphenyl-2-picrylhydrazyl radical scavenging
      assays. These results suggested that structural changes in quercetin induced by
      DBD plasma might be attributable to improving the biological activity.

PMID- 28745880
TI  - Organosilicon Radicals with Si-H and Si-Me Bonds from Commodity Precursors.
AB  - The cyclic alkyl(amino) carbene (cAAC) stabilized biradicals of composition
      (cAAC)2SiH2 (1), (cAAC)SiMe2-SiMe2(cAAC) (2), and (cAAC)SiMeCl-SiMeCl(cAAC) (3)
      have been isolated as molecular species. All the compounds are stable at room
      temperature for more than 6 months under inert conditions in the solid state. All
      radical species were fully characterized by single-crystal X-ray structure
      analysis and EPR spectroscopy. Furthermore, the structure and bonding of
      compounds 1-3 have been investigated by theoretical methods. Compound 1 contains
      the SiH2 moiety and this is the first instance, where we have isolated 1 without
      an acceptor molecule.

PMID- 28745881
TI  - Tunable White-Light Emission in Single-Cation-Templated Three-Layered 2D
      Perovskites (CH3CH2NH3)4Pb3Br10-xClx.
AB  - Two-dimensional (2D) hybrid halide perovskites come as a family (B)2(A)n
      1PbnX3n+1 (B and A= cations; X= halide). These perovskites are promising
      semiconductors for solar cells and optoelectronic applications. Among the
      fascinating properties of these materials is white-light emission, which has been
      mostly observed in single-layered 2D lead bromide or chloride systems (n = 1),
      where the broad emission comes from the transient photoexcited states generated
      by self-trapped excitons (STEs) from structural distortion. Here we report a
      multilayered 2D perovskite (n = 3) exhibiting a tunable white-light emission.
      Ethylammonium (EA+) can stabilize the 2D perovskite structure in EA4Pb3Br10-xClx
      (x = 0, 2, 4, 6, 8, 9.5, and 10) with EA+ being both the A and B cations in this
      system. Because of the larger size of EA, these materials show a high distortion
      level in their inorganic structures, with EA4Pb3Cl10 having a much larger
      distortion than that of EA4Pb3Br10, which results in broadband white-light
      emission of EA4Pb3Cl10 in contrast to narrow blue emission of EA4Pb3Br10. The
      average lifetime of the series decreases gradually from the Cl end to the Br end,
      indicating that the larger distortion also prolongs the lifetime (more STE
      states). The band gap of EA4Pb3Br10-xClx ranges from 3.45 eV (x = 10) to 2.75 eV
      (x = 0), following Vegard's law. First-principles density functional theory
      calculations (DFT) show that both EA4Pb3Cl10 and EA4Pb3Br10 are direct band gap
      semiconductors. The color rendering index (CRI) of the series improves from 66
      (EA4Pb3Cl10) to 83 (EA4Pb3Br0.5Cl9.5), displaying high tunability and versatility
      of the title compounds.

PMID- 28745882
TI  - Monomeric 16-Electron pi-Diborene Complexes of Zn(II) and Cd(II).
AB  - Despite the prevalence of stable pi-complexes of most d10 metals, such as Cu(I)
      and Ni(0), with ethylene and other olefins, complexation of d10 Zn(II) to simple
      olefins is too weak to form isolable complexes due to the metal ion's limited
      capacity for pi-backdonation. By employing more strongly donating pi-ligands,
      namely neutral diborenes with a high-lying pi(B?B) orbital, monomeric 16-electron
      M(II)-diborene (M = Zn, Cd) pi-complexes were synthesized in good yields. Metal
      B2 pi-interactions in both the solid and solution state were confirmed by single
      crystal X-ray analyses and their solution NMR and UV-vis absorption spectroscopy,
      respectively. The M(II) centers adopt a trigonal planar geometry and interact
      almost symmetrically with both boron atoms. The MB2 planes significantly twist
      out of the MX2 planes about the M-centroid(B-B) vector, with angles ranging from
      47.0 degrees  to 85.5 degrees , depending on the steric interactions between the
      diborene ligand and the MX2 fragment.

PMID- 28745883
TI  - Derivatization of Phosphine Ligands with Bulky Deltahedral Zintl Clusters
      Synthesis of Charge Neutral Zwitterionic Tetrel Cluster Compounds
      [(Ge9{Si(TMS)3}2)tBu2P]M(NHCDipp) (M: Cu, Ag, Au).
AB  - Reactions of silylated clusters [Ge9{Si(TMS)3}3]- or [Ge9{Si(TMS)3}2]2- with
      dialkylhalophosphines R2PCl (Cy, iPr, tBu) at ambient temperature yield the first
      tetrel Zintl cluster compounds bearing phosphine moieties. Varying reactivity of
      the dialkylhalophosphines toward the silylated clusters is observed depending on
      the bulkiness of the phosphine's alkyl substituents and on the number of
      hypersilyl groups at the tetrel cluster. Reactions between phosphines with small
      cyclohexyl- (Cy) or isopropyl- (iPr) groups and the tris-silylated cluster
      [Ge9{Si(TMS)3}3]- yield the novel neutral cluster compounds [Ge9{Si(TMS)3}3PR2]
      (R: Cy (1), iPr (2)) with discrete Ge-P exo bonds. By contrast, the bulkier
      phosphine tBu2PCl does not react with [Ge9{Si(TMS)3}3]- due to steric crowding.
      However, the reaction with the bis-silylated cluster [Ge9{Si(TMS)3}2]2- yields
      the novel cluster compound [Ge9{Si(TMS)3}2PtBu2]- (3). Subsequent reactions of
      compound 3 with NHCDippMCl (M: Cu, Ag, Au) yield the charge neutral zwitterionic
      compounds [(Ge9{Si(TMS)3}2)tBu2P]M(NHCDipp) (M: Cu, Ag, Au) (4-6), in which
      compound 3 acts as a phosphine ligand bearing a bulky tetrel Zintl cluster
      moiety. Compounds 4-6 also represent the first uncharged examples for 3-fold
      substituted tetrel Zintl clusters.

PMID- 28745884
TI  - Origins of Small Proton Chemical Shift Differences in Monodeuterated Methyl
      Groups.
AB  - We have recently shown that the small proton chemical shift difference in 2
      methyl-1-(methyl-d)piperidine supports a long-lived nuclear spin state. To
      identify additional candidate molecules with CH2D groups exhibiting accessible
      long-lived states, and to investigate the factors governing the magnitude of the
      shift differences, we report a computational and experimental investigation of
      methyl rotational equilibria and proton chemical shifts in a variety of 2
      substituted 1-(methyl-d)piperidines. The polarity and size of the 2-substituent
      affect the 1,2-stereoisomeric relationship, and consequently, the strength of the
      rotational asymmetry within the CH2D group. Nonpolar and large 2-substituents
      prefer the equatorial position, and relatively large shift differences (i.e., >
      13 ppb) are observed. Polar and small substituents, however, increasingly prefer
      the axial position, and medium to small shift differences (i.e., 0 to 9 ppb) are
      observed. In addition, the diastereotopic CH2D proton chemical shift difference
      for tricarbonyl(1-chloro-2-deuteriomethylbenzene) chromium(0) was computed,
      showing that reasonable predictions of these small shift differences can be
      extended to more complex, organometallic species.

PMID- 28745885
TI  - Chemical Synthesis Demonstrates That Dynamic O-Glycosylation Regulates the
      Folding and Functional Conformation of a Pivotal EGF12 Domain of the Human NOTCH1
      Receptor.
AB  - The interaction of the human NOTCH1 receptor and its ligands is a crucial step in
      initiating the intracellular signal transductions, in which O-glycosylation of
      the extracellular EGF-like domain strongly affects multiple aspects of cell
      differentiation, development, and cancer biology. However, consequences of
      biosynthetic O-glycosylation processes in the endoplasmic reticulum (ER) and
      Golgi on the folding of EGF domains remain unclear. Synthetic human NOTCH1 EGF12
      modules allow for new insight into the crucial roles of O-glycosylation in the
      folding and conformation of this pivotal domain. Here, we show for the first time
      that predominant O-glucosylation at Ser458 facilitates proper folding of the
      EGF12 domain in the presence of calcium ion, while the nonglycosylated linear
      EGF12 peptide affords large amounts of misfolded products (>50%) during in vitro
      oxidative folding. Strikingly, O-fucosylation at Thr466 prior to O-glucosylation
      at Ser458 totally impedes folding of EGF12 independent of calcium ion, whereas
      modification of the Fucalpha1-> moiety with beta-linked GlcNAc dramatically
      enhances folding efficiency. In addition, we elicit that extension of the
      Glcbeta1-> moiety with xyloses is a negative-regulation mechanism in the folding
      of EGF12 when synthesis of a trisaccharide (Xylalpha1->3Xylalpha1->3Glcbeta1->)
      dominates over the posttranslational modification at Thr466. Comprehensive
      nuclear magnetic resonance studies of correctly folded EGF12 modules demonstrate
      that noncovalently bonded bridges between sugars and peptide moieties, namely
      sugar bridges, contribute independently to the stabilization of the antiparallel
      beta-sheet in the ligand-binding region. Our results provide evidence that the
      dynamic O-glycosylation status of the EGF12 domain elaborated in the ER and Golgi
      strongly affects folding and trafficking of the human NOTCH1 receptor.

PMID- 28745886
TI  - Sulfoximidoyl-Containing Hypervalent Iodine(III) Reagents: 1-Sulfoximidoyl-1,2
      benziodoxoles.
AB  - Treatment of NH-sulfoximines with pseudocyclic benziodoxole triflate results in N
      I bond formation leading to a new type of sulfoximidoyl-containing hypervalent
      iodine(III) reagents in high yields. Degradation studies revealed a pronounced
      stability in both the solid state and in solution.

PMID- 28745887
TI  - Phthalazino[1,2-b]quinazolinones as p53 Activators: Cell Cycle Arrest, Apoptotic
      Response and Bak-Bcl-xl Complex Reorganization in Bladder Cancer Cells.
AB  - p53 inactivation is a clinically defined characteristic for cancer treatment
      nonresponsiveness. It is therefore highly desirable to develop anticancer agents
      by restoring p53 function.1 Herein the synthesized phthalazino[1,2
      b]quinazolinones were discovered as p53 activators in bladder cancer cells. 10
      Bromo-5-(2-dimethylamino-ethylamino)phthalazino[1,2-b]quinazolin-8-one (5da) was
      identified as the most promising candidate in view of both its anticancer
      activity and mechanisms of action. 5da exhibited strong anticancer activity on a
      broad range of cancer cell lines and significantly reduced tumor growth in
      xenograft models at doses as low as 6 mg/kg. Furthermore, 5da caused cell cycle
      arrest at S/G2 phase, induced apoptosis, changed cell size, and led to cell death
      by increasing the proportion of sub-G1 cells. Molecular mechanism studies
      suggested that accumulation of phospho-p53 in mitochondria after 5da treatment
      resulted in conformational activation of Bak, thereby evoking cell apoptosis,
      finally leading to irreversible cancer cell inhibition. Our present studies
      furnish new insights into the molecular interactions and anticancer mechanisms of
      phospho-p53-dependent quinazolinone compound.

PMID- 28745888
TI  - Route to Stable Lead-Free Double Perovskites with the Electronic Structure of
      CH3NH3PbI3: A Case for Mixed-Cation [Cs/CH3NH3/CH(NH2)2]2InBiBr6.
AB  - During the past year, halide double perovskites attracted attention as potential
      lead-free alternatives to Pb-based halide perovskites. However, none of the
      compounds discovered so far can match the optoelectronic properties of MAPbI3 (MA
      = CH3NH3). Here we argue that, from the electronic structure viewpoint, the only
      option to make Pb-free double perovskites retaining the remarkable properties of
      MAPbI3 is to combine In and Bi as B+ and B3+ cations, respectively. While
      inorganic double perovskites such as Cs2InBiX6 were found to be unstable due to
      In+ oxidizing into In3+, we show that the +1 oxidation state of In becomes
      progressively more stable as the A-site cation changes from K to Cs. Hence, we
      propose the use of MA and FA [FA = CH(NH2)2] to stabilize A2InBiBr6 double
      perovskites. We show that the optoelectronic properties of MA2InBiBr6 are
      remarkably similar to those of MAPbI3 and explore the mixed-cation
      (Cs/MA/FA)2InBiBr6 halide double perovskites.

PMID- 28745889
TI  - Nanosheet Supported Single-Metal Atom Bifunctional Catalyst for Overall Water
      Splitting.
AB  - Nanosheet supported single-atom catalysts (SACs) can make full use of metal atoms
      and yet entail high selectivity and activity, and bifunctional catalysts can
      enable higher performance while lowering the cost than two separate unifunctional
      catalysts. Supported single-atom bifunctional catalysts are therefore of great
      economic interest and scientific importance. Here, on the basis of first
      principles computations, we report a design of the first single-atom bifunctional
      eletrocatalyst, namely, isolated nickel atom supported on beta12 boron monolayer
      (Ni1/beta12-BM), to achieve overall water splitting. This nanosheet supported SAC
      exhibits remarkable electrocatalytic performance with the computed overpotential
      for oxygen/hydrogen evolution reaction being just 0.40/0.06 V. The ab initio
      molecular dynamics simulation shows that the SAC can survive up to 800 K elevated
      temperature, while enacting a high energy barrier of 1.68 eV to prevent isolated
      Ni atoms from clustering. A viable experimental route for the synthesis of
      Ni1/beta12-BM SAC is demonstrated from computer simulation. The desired nanosheet
      supported single-atom bifunctional catalysts not only show great potential for
      achieving overall water splitting but also offer cost-effective opportunities for
      advancing clean energy technology.

PMID- 28745890
TI  - The Role of Thermal Activation and Molecular Structure on the Reaction of
      Molecular Surfaces.
AB  - Though surface modifications of organic thin films dramatically improve
      optoelectronic device performance, chemistry at organic surfaces presents new
      challenges that are not seen in conventional inorganic surfaces. This work
      demonstrates that the subsurface of pentacene remains highly accessible, even to
      large adsorbates, and that three distinct reaction regimes (surface, subsurface,
      and bulk) are accessed within the narrow thermal range of 30-75  degrees C.
      Progression of this transition is quantitatively measured via polarization
      modulation infrared reflection absorption spectroscopy, and atomic force
      microscopy is used to measure the thin-film morphology. Together, they reveal the
      close relationship between the extent of the reaction and the morphology changes.
      Finally, the reaction kinetics of the pentacene thin film is measured with a
      series of adsorbates that have different reactivity and diffusivity in the thin
      film. The results suggest that reaction kinetics in the thin film is controlled
      by both the reactivity and the adsorbate diffusivity in the thin-film lattice,
      which is very different than the traditional solution kinetics that is dominated
      by the chemical activation barriers. Combined, these experiments guide efforts
      toward rationally functionalizing the surfaces of organic semiconductors to
      enable the next generation of flexible devices.

PMID- 28745891
TI  - Secondary Electron Cloaking with Broadband Plasmonic Resonant Absorbers.
AB  - Scanning electron microscopy (SEM) is one of the most powerful tools for
      nanoscale inspection and imaging. It is broadly used for biomedicine, materials
      science, and nanotechnology, enabling spatial resolution beyond the optical
      diffraction limit. In SEM, a high-energy electron beam illuminates a specimen,
      and the emitted secondary electrons are routed to a positively biased,
      synchronized detector for image creation. Here, for the first time, we
      experimentally demonstrate a cloaking of metallic objects from a secondary
      electron image. We make a metallic disc with a diameter of 300 nm almost
      invisible to a secondary electron detector with <5 nm spatial resolution. The
      secondary electron cloaking is based on broadband optical radiation absorption in
      the near field. Our secondary electron images are in good agreement with full
      wave numerical solution of Maxwell's equations at optical frequencies, confirming
      the concept of secondary electron cloaking based on broadband optical radiation
      absorption.

PMID- 28745892
TI  - Silica-Coated Core-Shell Structured Polystyrene Nanospheres and Their Size
      Dependent Mechanical Properties.
AB  - The core-shell structured PS/SiO2 composite nanospheres were synthesized on the
      basis of a modified Stober method. The mechanical properties of monodisperse
      nanospheres were characterized with nanoindentation on the basis of the atomic
      force microscopy (AFM). The surface morphologies of PS/SiO2 composite nanospheres
      was scanned with the tapping mode of AFM, and the force-distance curves were
      measured with the contact mode of AFM. Different contact models were compared for
      the analyses of experimental data. The elastic moduli of PS/SiO2 composite
      nanosphere (4-40 GPa) and PS nanosphere (~3.4 GPa) were obtained with the Hertz
      and Johnson-Kendall-Roberts (JKR) models, respectively, and the JKR model was
      proven to be more appropriate for calculating the elastic modulus of PS/SiO2
      nanospheres. The elastic modulus of SiO2 shell gradually approached a constant
      value (~46 GPa) with the increase of SiO2 shell thickness. A core-shell model was
      proposed for describing the relationship between PS/SiO2 composite nanosphere's
      elastic modulus and shell thickness. The mechanical properties of the composite
      nanospheres were reasonably explained on the basis of the growth mechanism of
      PS/SiO2 composite nanospheres, in particular the SiO2 shell's formation process.
      Available research data of PS/SiO2 composite nanospheres in this work can provide
      valuable guidance for their effective application in surface engineering,
      micro/nanomanufacturing, lubrication, and so on.

PMID- 28745893
TI  - Microbiota-Host Transgenomic Metabolism, Bioactive Molecules from the Inside.
AB  - Molecular factors from the gut microbiota provide the host with the right
      metabolic, immunological, and neurological components to support health and well
      being. However, certain circumstances can rupture the mutualistic pact with our
      intestinal counterpart, pushing the gut microbiome toward a dysbiotic layout,
      where microbiome-derived molecules may contribute to a disease state. We are now
      beginning to understand the microbiota-host co-regulated pathways underlying
      these processes, paving the way for a new era of rational piloting of the gut
      microbiome functions, through the design of a new generation of microbiome
      targeting drugs. Microbiota-derived metabolites are emerging as promising
      starting hit compounds to modulate human targets, hence triggering certain
      pharmacological responses. In conclusion, drug discovery targeting the gut
      microbiota as well as the characterization of microbiota-derived metabolites can
      represent innovative medicinal chemistry possibilities toward the identification
      of novel drug candidates, targets, and more in general innovative ways for the
      treatment of unmet medical needs.

PMID- 28745894
TI  - Phase Evolution, Crystal Structure, and Microwave Dielectric Properties of Water
      Insoluble (1 - x)LaNbO4-xLaVO4 (0 <= x <= 0.9) Ceramics.
AB  - In the present work, a series of low-temperature firing scheelite structured
      microwave dielectric in water-insoluble La2O3-Nb2O5-V2O5 system was prepared via
      the traditional solid-state reaction method. Backscattering electron diffraction,
      X-ray diffraction (XRD), energy-dispersive analysis, and Rietveld refinements
      were performed to study the phase evolution and crystal structure. In the full
      composition range of (1 - x)LaNbO4-xLaVO4 (0 <= x <= 0.9) ceramics, at least four
      typical phase regions including monoclinic fergusonite, tetragonal sheelite, B
      site ordered sheelite, and composite of monoclinic LaVO4 and tetragonal sheelite
      phases can be detected according to XRD analysis. The variations of relative
      dielectric constant epsilonr, quality factor Q * f, and resonant frequency tauf
      could be attributed to Nb/V-O bond ionicity, lattice energy, and the coefficient
      of thermal expansion. Infrared reflectivity spectra analysis revealed that ion
      polarization contributed mainly to the permittivity in microwave frequencies
      ranges. Furthermore, the 0.7LaNbO4-0.3LaVO4 ceramic sintered at 1160  degrees C
      possessed excellent microwave dielectric properties with an epsilonr of ~17.78, a
      Q * f of ~75 940 GHz, and a tauf of ca. -36.8 ppm/ degrees C. This series of
      materials might be good candidate for microwave devices.

PMID- 28745895
TI  - Reactivity of Triplet Excited States of Dissolved Natural Organic Matter in
      Stormflow from Mixed-Use Watersheds.
AB  - Dissolved organic matter (DOM) quantity and composition control the rate of
      formation (Rf,T) of triplet excited states of dissolved natural organic matter
      (3DOM*) and the efficiency of 3DOM* formation (the apparent quantum yield, AQYT).
      Here, the reactivity of 3DOM* in stormflow samples collected from watersheds with
      variable land covers is examined. Stormflow DOM reflects variability in DOM
      quantity and composition as a function of land cover and may be important in
      controlling the fate of cotransported pollutants. Rf,T and AQYT were measured
      using 2,4,6-trimethylphenol in stormflow samples under simulated sunlight. The
      DOM source and composition was characterized using absorbance and fluorescence
      spectroscopies and high-resolution mass spectrometry. Rf,T and the total rate of
      light absorption by the water samples (Ra) increased with the dissolved organic
      carbon (DOC) concentration. AQYT was independent of DOC concentration, but varied
      with DOM source: developed land cover (4-6%) ~ open water > vegetated land cover
      (3%). AQYT was positively related to an index for microbial/algal DOM content and
      negatively related to DOM molecular weight, DOM aromaticity, and the content of
      polyphenols. This work demonstrates that TMP is an effective probe for the
      determination of Rf,T and AQYT in whole water samples after accounting for the
      inhibition of TMP photodegradation by DOM.

PMID- 28745896
TI  - Carboxymethylpullulan Grafted with Aminoguaiacol: Synthesis, Characterization,
      and Assessment of Antibacterial and Antioxidant Properties.
AB  - Aminoguaiacol, the aminated derivative of guaiacol, a natural phenolic compound,
      was chemically grafted onto a polysaccharide (carboxymethylpullulan, CMP) in the
      presence of the activator agent 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide
      hydrochloride (EDCI). The grafted polysaccharides were characterized by FTIR and
      1H NMR spectroscopy to confirm and quantify the grafting. All polysaccharide
      derivatives (grafting rates of aminoguaiacol between 16% and 58%) were soluble in
      water. Their physicochemical properties were studied in a dilute regime and a
      semidilute regime by light scattering, fluorescence, and rheology, showing
      associative properties with peculiar polysoap behavior. The antibacterial
      activities of the synthesized products against Staphyloccocus aureus were
      assessed using a counting method. The antioxidant activities of the derivatives
      were also highlighted using the alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH)
      method. Finally, the cytotoxicity of the derivatives was studied with fibroblast
      cells and they showed a very good cytocompatibility. Such polymers could be used
      to replace chemical preservatives in food and cosmetic aqueous formulations.

PMID- 28745897
TI  - Incorporating Transgenerational Epigenetic Inheritance into Ecological Risk
      Assessment Frameworks.
AB  - Chronic exposure to environmental contaminants can induce heritable
      "transgenerational" modifications to organisms, potentially affecting future
      ecosystem health and functionality. Incorporating transgenerational epigenetic
      heritability into risk assessment procedures has been previously suggested.
      However, a critical review of existing literature yielded numerous studies
      claiming transgenerational impacts, with little compelling evidence. Therefore,
      contaminant-induced epigenetic inheritance may be less common than is reported in
      the literature. We identified a need for multigeneration epigenetic studies that
      extend beyond what could be deemed "direct exposure" to F1 and F2 gametes and
      also include subsequent multiple nonexposed generations to adequately evaluate
      transgenerational recovery times. Also, increased experimental replication is
      required to account for the highly variable nature of epigenetic responses and
      apparent irreproducibility of current studies. Further, epigenetic end points
      need to be correlated with observable detrimental organism changes before a need
      for risk management can be properly determined. We suggest that epigenetic-based
      contaminant studies include concentrations lower than current "EC10-20" or
      "Lowest Observable Effect Concentrations" for the organism's most sensitive
      phenotypic end point, as higher concentrations are likely already regulated.
      Finally, we propose a regulatory framework and optimal experimental design that
      enables transgenerational epigenetic effects to be assessed and incorporated into
      conventional ecotoxicological testing.

PMID- 28745898
TI  - Development of a Mitochondriotropic Antioxidant Based on Caffeic Acid: Proof of
      Concept on Cellular and Mitochondrial Oxidative Stress Models.
AB  - Targeting mitochondrial oxidative stress is an effective therapeutic strategy. In
      this context, a rational design of mitochondriotropic antioxidants (compounds 22
      27) based on a dietary antioxidant (caffeic acid) was performed. Jointly named as
      AntiOxCINs, these molecules take advantage of the known ability of the
      triphenylphosphonium cation to target active molecules to mitochondria. The study
      was guided by structure-activity-toxicity-property relationships, and we
      demonstrate in this work that the novel AntiOxCINs act as mitochondriotropic
      antioxidants. In general, AntiOxCINs derivatives prevented lipid peroxidation and
      acted as inhibitors of the mitochondrial permeability transition pore. AntiOxCINs
      toxicity profile was found to be dependent on the structural modifications
      performed on the dietary antioxidant. On the basis of mitochondrial and
      cytotoxicity/antioxidant cellular data, compound 25 emerged as a potential
      candidate for the development of a drug candidate with therapeutic application in
      mitochondrial oxidative stress-related diseases. Compound 25 increased GSH
      intracellular levels and showed no toxicity on mitochondrial morphology and
      function.

PMID- 28745899
TI  - An Approach to 3-(Indol-2-yl)succinimide Derivatives by Manganese-Catalyzed C-H
      Activation.
AB  - The manganese-catalyzed addition of C-2 position of indoles to maleimides has
      been achieved under additive-free conditions. The manganese catalyst exhibits
      excellent chemo- and regioselectivity, good functional group compatibility, and
      high catalytic efficiency. The substrate scope can also be extended to maleates,
      ethyl acrylate, 1,4-dihydro-1,4-epoxynaphthalene, pyrroles, and 2-phenylpyridine,
      which further demonstrates the universality of this straightforward approach.

PMID- 28745900
TI  - Full Wave Function Optimization with Quantum Monte Carlo and Its Effect on the
      Dissociation Energy of FeS.
AB  - Diffusion quantum Monte Carlo calculations with partial and full optimization of
      the guide function are carried out for the dissociation of the FeS molecule. For
      the first time, quantum Monte Carlo orbital optimization for transition metal
      compounds is performed. It is demonstrated that energy optimization of the
      orbitals of a complete active space wave function in the presence of a Jastrow
      correlation function is required to obtain agreement with the experimental
      dissociation energy. Furthermore, it is shown that orbital optimization leads to
      a 5Delta ground state, in agreement with experiments but in disagreement with
      other high-level ab initio wave function calculations which all predict a 5Sigma+
      ground state. The role of the Jastrow factor in DMC calculations with
      pseudopotentials is investigated. The results suggest that a large Jastrow factor
      may improve the DMC accuracy substantially at small additional cost.

PMID- 28745901
TI  - Prevalence and Years Lived with Disability of 310 Diseases and Injuries in Iran
      and its Neighboring Countries, 1990-2015: Findings from Global Burden of Disease
      Study 2015.
AB  - BACKGROUND: Due to significant achievements in reducing mortality and increasing
      life expectancy, the issue of disability from diseases and injuries, and their
      related interventions, has become one of the most important concerns of health
      related research. METHODS: Using data obtained from the GBD 2015 study, the
      present report provides prevalence and years lived with disability (YLDs) of 310
      diseases and injuries by sex and age in Iran and neighboring countries over the
      period 1990-2015. Age-standardized rates of all causes of YLDs are presented for
      both males and females in 16 countries for 1990 and 2015. We present the
      percentage of total YLDs for 21 categories of diseases and injuries, the
      percentage of YLDs for age groups, as well as the ranking of the most prevalent
      causes and YLDs from the top 50 diseases and injuries in Iran. RESULTS: In 2015,
      the burden of 310 diseases and injuries among the Iranian population was
      responsible for 8,357,878 loss of all-age total years, which is equal to 10.58%
      of total years lived per year. This differs from the neighboring countries, as it
      ranges from 9.05% in Turkmenistan to 13.36% in Russia. During the past 25 years,
      a remarkable decrease was observed in all-cause YLD rates in all 16 countries.
      Meanwhile, in all countries, the age-standardized rate of all causes of YLDs was
      higher in females than males. CONCLUSION: Based on our findings, one of the
      remarkable changes in NCDs observed among the studied age groups was increased
      rate of YLDs from mental disorders, which was replaced by musculoskeletal
      disorders in older age groups in 2015.

PMID- 28745902
TI  - Disability-Adjusted Life-Years (DALYs) for 315 Diseases and Injuries and Healthy
      Life Expectancy (HALE) in Iran and its Neighboring Countries, 1990-2015: Findings
      from Global Burden of Disease Study 2015.
AB  - BACKGROUND: Summary measures of health are essential in making estimates of
      health status that are comparable across time and place. They can be used for
      assessing the performance of health systems, informing effective policy making,
      and monitoring the progress of nations toward achievement of sustainable
      development goals. The Global Burden of Diseases, Injuries, and Risk Factors
      Study 2015 (GBD 2015) provides disability-adjusted life-years (DALYs) and healthy
      life expectancy (HALE) as main summary measures of health. We assessed the trends
      of health status in Iran and 15 neighboring countries using these summary
      measures. METHODS: We used the results of GBD 2015 to present the levels and
      trends of DALYs, life expectancy (LE), and HALE in Iran and its 15 neighboring
      countries from 1990 to 2015. For each country, we assessed the ratio of observed
      levels of DALYs and HALE to those expected based on socio-demographic index
      (SDI), an indicator composed of measures of total fertility rate, income per
      capita, and average years of schooling. RESULTS: All-age numbers of DALYs reached
      over 19 million years in Iran in 2015. The all-age number of DALYs has remained
      stable during the past two decades in Iran, despite the decreasing trends in all
      age and age-standardized rates. The all-cause DALY rates decreased from 47,200 in
      1990 to 28,400 per 100,000 in 2015. The share of non-communicable diseases in
      DALYs increased in Iran (from 42% to 74%) and all of its neighbors between 1990
      and 2015; the pattern of change is similar in almost all 16 countries. The DALY
      rates for NCDs and injuries in Iran were higher than global rates and the average
      rate in High Middle SDI countries, while those for communicable, maternal,
      neonatal, and nutritional disorders were much lower in Iran. Among men,
      cardiovascular diseases ranked first in all countries of the region except for
      Bahrain. Among women, they ranked first in 13 countries. Life expectancy and HALE
      show a consistent increase in all countries. Still, there are dissimilarities
      indicating a generally low LE and HALE in Afghanistan and Pakistan and high
      expectancy in Qatar, Kuwait, and Saudi Arabia. Iran ranked 11th in terms of LE at
      birth and 12th in terms of HALE at birth in 1990 which improved to 9th for both
      metrics in 2015. Turkey and Iran had the highest increase in LE and HALE from
      1990 to 2015 while the lowest increase was observed in Armenia, Pakistan, Kuwait,
      Kazakhstan, Russia, and Iraq. CONCLUSIONS: The levels and trends in causes of
      DALYs, life expectancy, and HALE generally show similarities between the 16
      countries, although differences exist. The differences observed between countries
      can be attributed to a myriad of determinants, including social, cultural,
      ethnic, religious, political, economic, and environmental factors as well as the
      performance of the health system. Investigating the differences between countries
      can inform more effective health policy and resource allocation. Concerted
      efforts at national and regional levels are required to tackle the emerging
      burden of non-communicable diseases and injuries in Iran and its neighbors.

PMID- 28745903
TI  - Trend of Socio-Demographic Index and Mortality Estimates in Iran and its
      Neighbors, 1990-2015; Findings of the Global Burden of Diseases 2015 Study.
AB  - BACKGROUND: The Global burden of disease and injuries study (GBD 2015) reports
      expected measures for years of life lost (YLL) based on socio-demographic index
      (SDI) of countries, as well as the observed measures. In this extended GBD 2015
      report, we reviewed total and cause-specific deaths and YLL for Iran and all its
      neighboring countries between 1990 and 2015. METHODS: We extracted data from the
      GBD 2015 database. Observed YLL measures were calculated by multiplying the
      number of deaths by standard life expectancy at each age. SDI was a composite
      index, calculated based on income per capita, average years of schooling, and
      total fertility rate. The GBD world population was used for age standardization.
      RESULTS: All-ages crude death rate in Iran reduced from 665.6 per 100,000
      population (95% uncertainty interval: 599.3-731.6) in 1990 to 487.2 (414.9-566.1)
      in 2015. The ratio of observed to expected YLL (O/E ratio) for all-causes ranged
      between 0.54 (Turkey) and 1.95 (Russia) in 2015. For Iran, the all-causes O/E
      ratio was less than 1 in all years (1990-2015), except 2003. However, cause
      specific O/E ratio was more than 1 for some causes, including the top leading
      causes of YLL (ischemic heart disease, road injuries, and cerebrovascular
      disorders). Ischemic heart disease was the first or second cause of YLL in all
      comparator countries except Afghanistan. CONCLUSION: The leading YLL causes with
      high O/E ratios should be prioritized in public health efforts. In addition to
      research evidence, countries with low O/E ratios should be scrutinized to find
      feasible innovative interventions.

PMID- 28745904
TI  - Burden of Skin and Subcutaneous Diseases in Iran and Neighboring Countries:
      Results from the Global Burden of Disease Study 2015.
AB  - BACKGROUND: Iran and its neighboring countries represent four world regions with
      unique cultures and geography. Skin diseases span a wide diversity of etiologies
      including infectious, inflammatory, autoimmune, vascular, neurogenic, and
      oncologic. The Global Burden of Disease Study (GBD) 2015 measures the burden from
      skin diseases in 195 countries. METHODS: Epidemiologic data were collected from
      literature review, survey data, and hospital inpatient/outpatient claims data.
      These raw data entered modeling using a Bayesian meta-regression tool, DisMod MR
      2.1, which yielded prevalence estimates by age/sex/location/year. Prevalence
      estimates were combined with disability weights to yield years lived with
      disability (YLDs). YLDs are combined with years of life lost (YLLs), from
      mortality estimates, to yield disability-adjusted life years (DALYs). DALYs were
      obtained for 16 skin conditions and both sexes in Iran and 15 surrounding
      countries. The sociodemographic index (SDI) for each country was also correlated
      with skin disease DALY rate using the Pearson coefficient (r) with two-tailed P
      value. RESULTS: There was no significant correlation between individual skin
      diseases and SDI. Acne and dermatitis caused the greatest burden and BCC the
      lowest burden of skin diseases in Iran and the other 15 countries. SCC and BCC
      were responsible for the largest discrepancy by sex, with higher burden in males
      compared to females. CONCLUSION: Skin diseases, particularly dermatitis and acne,
      cause considerable burden in Iran and surrounding regions. Objective and
      transparent epidemiologic data such as GBD has the potential to inform and impact
      many facets of healthcare, research prioritization, public policy, and
      international partnerships.

PMID- 28745905
TI  - Seroprevalence of Anti-Toxoplasma Gondii Antibodies in Healthy Voluntary Blood
      Donors from Mashhad City, Iran.
AB  - OBJECTIVE: The present investigation aims to evaluate the prevalence of IgM and
      IgG anti-T. gondii antibodies and the associated risk factors among healthy blood
      donors in Mashhad city, Razavi Khorasan province, Iran. METHODS: We screened a
      total of 500 serum samples by census method from apparently healthy blood donors
      of the Mashhad Blood Transfusion Organization (MBTO) for IgG and IgM anti-T.
      gondii antibodies by enzyme linked immunosorbent assay (ELISA). RESULTS: We found
      that 29.6%, 25%, 1.4%, and 3.2% of tested donors were positive for anti-T. gondii
      antibodies, only IgG antibody, both IgM and IgG, and IgM antibody alone,
      respectively. Several risk factors which were significantly related to T. gondii
      seropositivity in the univariate analysis at P < 0.05 included female gender (OR
      = 3.222, P < 0.001), age more than 40 years (P = 0.026), and sausage/hot dog
      consumption (OR = 4.472, P < 0.001). CONCLUSIONS: The results of this study can
      be a warning for blood transfusion organizations to pay special attention to
      toxoplasmosis among blood donors and also design screening programs for
      prevention of transfusion-transmitted toxoplasmosis.

PMID- 28745906
TI  - Challenges of Family Physician Program in Urban Areas: A Qualitative Research.
AB  - BACKGROUND: Family physicians play an essential role and act as a communicational
      bridge between people and the healthcare system in providing healthcare services
      efficiently and equitably. This study aimed at exploring the challenges of the
      family physician program in urban areas in Iran in 2015. METHODS: This research
      had a descriptive exploratory design with a qualitative content analysis
      approach. Data were collected through semi-structured interviews between 2014 and
      2015. Seventeen physicians enrolling in family physician program for at least two
      years were selected through purposeful sampling. Conventional content analysis
      was used to analyze the data. FINDING: Coding and analysis of the interview data
      generated two categories and seven subcategories related to the challenges of the
      family physician program. The categories were poor infrastructure and poor
      incentive mechanism. CONCLUSION: Our findings captured a good picture of family
      physician program in urban areas to better clarify the challenges of the program
      and provide a foundation to plan and implement appropriate changes. Thus, our
      findings will give policymakers a deeper perception to confront the challenges of
      the family physician program in urban areas.

PMID- 28745907
TI  - Role of FDG PET/CT Scan in Head and Neck Cancer Patients.
AB  - INTRODUCTION: PET/CT scan has an emerging role in head and neck oncology with a
      few well-established indications, including: detection of unknown primary tumor
      site, tumor staging, radiotherapy planning, treatment response assessment and
      detection of recurrent disease. The purpose of this study is reporting PET/CT
      findings in head and neck cancer patients to emphasize its role in head and neck
      oncology. MATERIALS AND METHODS: In a retrospective study, we reviewed our PET/CT
      database and found 94 patients with primary head and neck cancer. This is a
      descriptive report of PET/CT scan findings in head and neck cancer patients
      referred to Masih Daneshvari hospital, Tehran, Iran between 2013 and 2016.
      RESULTS: The most common primary tumor sites were oral cavity (27%) and
      nasopharynx (22%). The most common indication for referral was tumor restaging
      (76%) including treatment response evaluation and differentiation between
      recurrence and post-treatment fibrosis. In 60% of patients with negative primary
      tumor site, PET/CT was able to detect evidence of regional or distant metastasis.
      PET/CT was able to localize the primary tumor site in 66% of patients with
      unknown primary tumor site. We also had 19 patients with primary head and neck
      cancer referred for initial staging, demonstrating evidence of metastasis in 66%
      of all cases. CONCLUSION: Most patients are referred for restaging and
      demonstrate evidence of regional or distant metastasis with significant value for
      further treatment planning. Providing insurance coverage and familiarizing
      referring physicians about correct indications of this relatively new diagnostic
      modality will be to the best interest of head and neck cancer patients in the
      long run.

PMID- 28745908
TI  - The Historical Background of Plaster Cast.
AB  - The pivotal role of plaster of Paris (POP) cast as an immobilization tool to
      promote healing in complex and/or other types of fractures is irrefutable. We
      clearly know that Antonius Mathysen extensively applied plaster cast during
      Crimea and/or other wars and reportedly saved thousands of lives. However, the
      exact origin of using POP in orthopedic cast is yet to be clear. In his famous
      report from Bandar-e Rig, a city in Iran, William Eton paved the way for the
      conclusion that POP cast might have originated from the Persian Empire. In this
      paper, we provide more supporting evidences which make the aforementioned claim
      more probable.

PMID- 28745909
TI  - The Role of Publishers in Prevention of Misconducts in Medical Research: Springer
      and BioMed Central, Victim or Culprit.

PMID- 28745911
TI  - If a Global Catastrophic Biological Risk Materializes, at What Stage Will We
      Recognize It?

PMID- 28745912
TI  - Impact of Psychological Grief Counseling on the Severity of Post-Traumatic Stress
      Symptoms in Mothers after Stillbirths.
AB  - Planned support and interventions are necessary in the care and support of women
      who have experienced stillbirth. The present study was conducted to determine the
      effect of psychological grief counseling on the symptom severity of post
      traumatic stress disorder (PTSD) in mothers after stillbirths. This
      interventional study is semi-experimental. The study was conducted on 100 women
      who had recently had stillbirths. Eligible samples were selected and randomly
      divided into the two groups of intervention and control. The data collection tool
      was the PPQ,1 which was completed as a pre-test and post-test in both groups. The
      intervention group received four sessions of psychological grief counseling over
      two weeks, and the control group received only routine postnatal care. PTSD
      severity was evaluated in both groups at the end of the fourth week after the
      final session. The results showed that there was a statistically significant
      difference in the mean score of the severity of the PTSD symptoms in both groups
      after the intervention (P = 0.0001), which means that psychological grief
      counseling led to the reduction of PTSD severity in mothers. Given the positive
      impact of psychological grief counseling on reducing the severity of PTSD,
      integration of intensive psychological interventions in the maternity care system
      seems essential for faster transition of grief stages and for the prevention of
      severe cases of PTSD.

PMID- 28745913
TI  - A Dry Method for Preserving Tear Protein Samples.
AB  - Tears covering the ocular surface are important biofluids containing thousands of
      molecules, including proteins, lipids, metabolites, nucleic acids, and
      electrolytes. Tears are valuable resources for biomarker research of ocular and
      even systemic diseases. For application in biomarker studies, tear samples should
      ideally be stored using a simple, lowcost, and efficient method along with the
      patient's medical records. For this purpose, we developed a novel Schirmer's
      strip-based dry method that allows for storage of tear samples in vacuum bags at
      room temperature. Using this method, tear protein patterns can also be preserved.
      Liquid chromatography-mass spectrometry/mass spectrometry analysis of proteins
      recovered by the dry method and traditional wet method showed no significant
      difference. Some tissue/organ-enriched proteins were identified in tear samples,
      thus tears might be a good window for monitoring changes of these tissues or
      organs. This dry method facilitates sample transportation and enables the storage
      of tear samples on a large scale, increasing the availability of samples for
      studying disease biomarkers in tears.

PMID- 28745914
TI  - Staying Awake and Aware: The Importance of Sleep in Psychiatric Nursing Practice.
AB  - Given that approximately 70 million Americans suffer from sleep-wake disorders
      and their under-recognized role in practice, psychiatric nurses may see, or may
      be already seeing, patients with undiagnosed sleep disorders. Assessment of sleep
      wake disorders can and should be a part of psychiatric nursing education and
      practice. Many practicing clinicians lack formal training regarding sleep-wake
      issues and treatment. Even as sleep disturbances are common concerns among
      psychiatric populations, sleep-wake issues may go unrecognized. The article
      presents a stylized progression of care to enable clinicians to identify,
      address, and treat underlying sleep-wake disorders in psychiatric settings. The
      article recommends instituting screening procedures for sleep-wake issues and
      follow-up assessments, particularly overnight pulse oximetry and polysomnograms.
      Just as clinicians already screen for physical conditions that would affect
      psychiatric care, practitioners can evaluate patients for potential sleep-wake
      disorders as part of their existing practice and intake procedures. Further, the
      piece details implications for psychopharmacology as well as evidence from
      clinical practice. Psychiatric nurses should stay awake to the importance of
      sleep medicine and aware of how sleep-wake disorders can affect psychiatric
      populations.

PMID- 28745915
TI  - Psychiatric Comorbidities and BMI: An Exploratory Analysis.
AB  - Years of research and clinical practice have demonstrated that individuals with
      certain mental health conditions are at an increased risk of obesity. However, no
      identified research has examined associations between multiple comorbid
      psychiatric disorders and body mass index (BMI). This study uses a secondary
      analysis to examine associations between a large number of combinations of
      various mental health conditions and BMI. Surprisingly, the results of this study
      indicate that the most comorbid psychiatric disorders are not associated with an
      increased risk of elevated BMI. However, bipolar disorder, agoraphobia, attention
      deficit hyperactivity disorder, and panic disorder had the greatest number of
      comorbid disorder associations linked with elevated BMI. The effect sizes ranged
      from a significant but relatively small Cohen's d of 0.3 to a more notable effect
      size of 0.7. The results of this study indicate that practitioners should be
      especially vigilant in helping their patients to avoid weight gain when they have
      one of the four identified disorders in combination with at least one other
      disorder. Future research is needed to understand the mechanisms underlying this
      increased risk and evaluate targeted interventions that would be the most
      effective for people with these diagnoses.

PMID- 28745916
TI  - Experiences and Perceived Social Support among Iranian Men on Methadone
      Maintenance Therapy: A Qualitative Study.
AB  - The use of drugs predominantly among Iranian men leads to health and social
      problems. Iran has established methadone maintenance therapy centres but there is
      limited research exploring the experiences of men who make use of this therapy.
      The aim of this qualitative study was to explore the experiences of men on
      methadone maintenance therapy in Urmia, Iran. Sixteen opioid-dependent males on
      methadone syrup substitution therapy were interviewed. Transcribed data were
      subjected to thematic analysis. Three themes emerged from the data: (1) the role
      of family in drug addiction; (2) the role of environment in drug addiction; and
      (3) the support needed to overcome drug addiction. While drug rehabilitation
      programmes in Iran can help the person, their family is seen as the most
      important support that they need together with sociocultural acceptance to
      overcome stigmatisation.

PMID- 28745917
TI  - The Meaning of Stigma for People with Mental Disorders in Brazil.
AB  - OBJECTIVE: To understand the meaning of stigma for people with mental disorders.
      METHOD: A qualitative study with 46 Brazilian adults with mental disorders. Data
      were collected through semistructured interviews and nonparticipant observation
      and submitted for a thematic analysis with symbolic interactionism. RESULTS:
      Stigma was considered as an experience of incomprehension and suffering. The
      society has difficulty in empathizing, respecting differences and understanding
      the extent of the suffering of people with mental disorders. Participants
      recommended anti-stigma strategies that included promoting knowledge and
      respecting differences. CONCLUSIONS: The present study contributes new insights
      to be addressed in interventions to reduce the suffering and impact of stigma.

PMID- 28745918
TI  - A systematic review about Streptococcus Pneumoniae serotype distribution in
      children in mainland of China before the PCV13 was licensed.
AB  - INTRODUCTION: Streptococcus pneumoniae (S. pneumoniae) is a major pathogen of
      infectious diseases in children. Surveillance of the distribution of pneumococcus
      serotypes is important for immunization strategies of pneumococcal polysaccharide
      conjugate vaccines (PCVs). Areas covered: This article is a systematic review of
      studies conducted from 2006 to 2016 that document serotypes of S. pneumoniae
      isolated from children less than 14 years old in the mainland of China. A total
      of 40 studies were included in this review. Serotypes 19F, 19A, 23F, 14 and 6B
      were the most common. Serotype prevalence and percentage varied by region and
      associated strains. The serotype coverage rate of PCV13 was higher than that of
      PCV10 due to the prevalence of serotype 19A, and there were no significant
      difference between the coverage rate of PCV13 and PPSV23. Expert commentary: To
      prevent Chinese children from S. pneumoniae infection, it is necessary for the
      universal immunization of PCV13 or develop new vaccines that include all the
      prevalent serotypes in China.

PMID- 28745919
TI  - A Risk Typology for Depression in African Americans.
AB  - Studies report that African Americans are likely to experience severe, chronic,
      and disabling depressive symptoms leading to poor depression outcomes. There are
      several psychosocial and sociocultural factors that individually contribute to
      depression in African Americans (i.e. chronic stress, negative life events,
      negative social interaction, social support, and religiosity). However, African
      Americans are a heterogeneous population and the identification of subpopulations
      with distinct constellations of multiple co-occurring risk and protective factors
      may offer greater explanatory potential into depression burden for African
      Americans. This study used data from the American's Changing Lives Survey to
      identify risk types for depression in a national sample of African American
      adults and older adults (n = 1174). Latent class analysis results revealed a risk
      typology that included 3 distinct risk patterns for African Americans.
      Individuals in the High Protective/Low Risk Type (41%) had high levels of
      religiosity and social support. Those in the Moderate Protection/Low Risk Type
      (44%) had moderate levels of religiosity and social support. The Low
      Protection/Low Risk Type (15%) had low organizational and non-organizational
      religiosity and relatively low social support. All three types were marked by
      relatively low risk factors (i.e. negative events, financial stress, and negative
      social interaction). Multinomial logistic regression results suggested
      associations between demographic characteristics (i.e. gender, age, education,
      marital status), depressive symptoms, and risk type. Study results have
      implications for the development of depression interventions that are targeted to
      a specific risk type and tailored to the demographic profile of individuals
      likely to experience poor depression outcomes.

PMID- 28745920
TI  - Reducing Global Catastrophic Biological Risks.

PMID- 28745921
TI  - Recovery-based Training in Mental Health: Effects on Staff Knowledge and
      Attitudes to Recovery.
AB  - This longitudinal study describes the effects of recovery-based training on staff
      knowledge and attitudes to recovery. Mental health staff (n = 101) completed the
      study questionnaire (the Recovery Knowledge Inventory (RKI-20) and Recovery
      Attitudes' Questionnaire (RAQ-16)) before training and after six months. On the
      RKI, significant changes between pre- and post-training scores (p < 0.01) were
      found. On the RAQ, the scores showed significant changes in Factors 1 (p < 0.001)
      and 2 (p < 0.009). The results indicate a significant difference in confidence
      using a recovery model of care following training suggesting that recovery-based
      training positively affects staff knowledge and attitudes to recovery overall.

PMID- 28745922
TI  - Exploration of the Factors Affecting the Choices of Nursing Students Who Choose
      Psychiatric Nursing as the First and Last Choice.
AB  - The aim of this qualitative study was to explore the factors that affect the
      choices of nursing students who chose a psychiatric nursing internship. The
      sample group of the study consisted of 13 students who listed psychiatric nursing
      as their first choice and 11 students who listed psychiatric nursing as their
      last choice. Four themes were determined: personal reasons, stigmatization,
      experiences related to psychiatric nursing, and perception of care. Providing
      activities in nursing education to reduce stigmatization and increasing the time
      allocated for psychiatric nursing theory and practice are recommended.

PMID- 28745923
TI  - Prevalence, Prevention, and Severity of Prescribing Errors in Different Years of
      Residency Training at an Oncology Ward.

PMID- 28745924
TI  - Global Catastrophic Biological Risks: Toward a Working Definition.

PMID- 28745925
TI  - Clinical care of children with primary ciliary dyskinesia.
AB  - INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare heterogeneous disorder,
      usually inherited as an autosomal recessive condition but X-linked inheritance is
      also described. Abnormal ciliary function in childhood leads to neonatal
      respiratory distress in term infants, persistent wet cough, bronchiectasis,
      chronic rhinosinusitis, and hearing impairment; approximately 50% of patients
      have situs inversus. There is a paucity of evidence for treating PCD, hence
      consensus guidelines are predominantly influenced by knowledge from cystic
      fibrosis (CF). Extrapolation of evidence from other diseases is inappropriate
      since differences in pathophysiology, morbidity and prognosis risk treatment
      failure and lack of adherence. Areas covered: Review authors searched PubMed and
      Cochrane databases for publications relating to management of children with PCD.
      Because of the paucity of data, we emphasise the need for well-designed clinical
      trials with PCD patients rather than reliance on evidence from other diseases.
      Expert commentary: The evidence for treatment of PCD is poor, and management is
      often extrapolated from studies of patients with CF or chronic rhinosinusitis.
      However, much work is underway to improve the situation and international
      consortia and networks are conducting well-designed projects to inform the
      management of children with PCD.

PMID- 28745926
TI  - Safety and efficacy of empirical interleukin-1 inhibition using anakinra in AA
      amyloidosis of uncertain aetiology.
AB  - OBJECTIVE: AA amyloidosis is a serious complication of persistent inflammation,
      which, untreated will progress to renal failure and death. Effective suppression
      of the underlying inflammatory disease is the focus of treatment. However, in
      approximately 20% of cases the underlying condition remains uncertain, presenting
      a dilemma as to choice of treatment. METHODS: We conducted a retrospective study
      of a cohort of 11 patients diagnosed with AA amyloidosis of unknown aetiology,
      who had been empirically treated with anakinra. RESULTS: In anakinra-responders,
      median pre-treatment SAA was 74 (IQR 34-190) mg/L, and median on-treatment SAA
      was 6 (4-16) mg/L (p = .0047), with the response having been maintained for a
      median on-treatment follow-up of 1.8 (1-7.6) years. Six dialysis patients were
      treated effectively and safely with 100 mg anakinra three times weekly post
      dialysis. Four patients remained well on daily anakinra post-renal transplant.
      Five anakinra-responders showed regression and three showed stabilization of
      amyloid load on serial SAP scintigraphy. CONCLUSIONS: This small cohort shows
      that even in potentially high risk cases with organ damage secondary to AA
      amyloidosis or in the presence of a renal graft, anakinra, when used
      appropriately and carefully monitored, has proved remarkably effective and well
      tolerated. Longer follow-up of this off-label use is required.

PMID- 28745927
TI  - Urine liver fatty acid binding protein and chronic kidney disease progression.
AB  - Excretion of the tubular protein liver fatty acid binding protein (L-FABP) is a
      potential novel biomarker of renal dysfunction. We examined whether urine L-FABP
      excretion adds prognostic information to the well-established risk markers, blood
      pressure (BP), albumin excretion and baseline GFR, regarding progression of
      chronic kidney disease (CKD). In a prospective study design a cohort of 74 stage
      3-4 CKD patients (age 61 +/- 13 years) were included. Glomerular filtration ratio
      (GFR, 51Cr-EDTA-clearance), 24-hour ambulatory BP, 24-hour urinary
      albumin/creatinine ratio (UAC) and urinary L-FABP/creatinine ratio (U-L-FABP/C)
      were determined at baseline and after 18 months of follow-up. For comparison 25
      age-matched healthy controls were included. The U-L-FABP/C was elevated in CKD
      patients when compared to controls (mean U-L-FABP/C 2.3 [95% CI 1.7-2.9] MUg/mmol
      vs 0.6 [0.5-0.7] MUg/mmol, p < .001). In CKD patients, log U-L-FABP/C at baseline
      and at follow-up were positively associated (Pearson correlation coefficient r =
      0.74, p < .001). Baseline log U-L-FABP/C was negatively correlated with baseline
      GFR (r = -0.32, p < .001) and directly correlated with UAC (r = 0.67, p < .001).
      The relative change in GFR from baseline to follow-up correlated with baseline
      UAC (p < .001), 24-hour systolic BP (p = 0.05) and log U-L-FABP/C (p < .001).
      Using multiple regression analysis adjusting for baseline GFR, UAC, BP, age and
      gender, baseline log U-L-FABP/C was associated with a decline in GFR only in
      patients with UAC <3 mg/mmol (n = 29, p = 0.001) and not in patients with UAC >=3
      mg/mmol (n = 44, p = 0.21). In conclusion urine L-FABP/C is permanently elevated
      in CKD patients, but only associated with GFR decline in those without
      albuminuria.

PMID- 28745928
TI  - Low-dose decitabine enhances chidamide-induced apoptosis in adult acute
      lymphoblast leukemia, especially for p16-deleted patients through DNA damage.
AB  - AIM: To investigate the combined action of decitabine (DAC) with chidamide
      (CS055) on acute lymphoblastic leukemia (ALL) cells. MATERIALS & METHODS: ALL
      cell lines as well as primary cells from 17 ALL patients were subjected to
      different treatments and thereafter cell counting Kit-8 (CCK-8) assay, flow
      cytometry and western blot were employed to determine IC50, apoptosis and
      checkpoint kinase 1 and gammaH2A.X expression. RESULTS: Low-dose DAC combined
      with CS055 could effectively kill ALL cells by the reduction of cell viability
      and induction of apoptosis. This was also observed in primary cells from 17 ALL
      patients, especially for those with p16 gene deletion. Suppression of checkpoint
      kinase 1 phosphorylation and upregulation of gammaH2A.X expression was
      demonstrated to participate in DAC plus CS055-induced apoptosis. CONCLUSION: Low
      dose DAC could enhance chidamide-induced apoptosis in adult ALL, especially for
      patients with p16 gene deletion through DNA damage.

PMID- 28745929
TI  - Molecular and Cellular Mechanisms of Palate Development.
AB  - Development of the mammalian secondary palate involves highly dynamic
      morphogenetic processes, including outgrowth of palatal shelves from the oral
      side of the embryonic maxillary prominences, elevation of the initially
      vertically oriented palatal shelves to the horizontal position above the
      embryonic tongue, and subsequently adhesion and fusion of the paired palatal
      shelves at the midline to separate the oral cavity from the nasal cavity.
      Perturbation of any of these processes could cause cleft palate, a common birth
      defect that significantly affects patients' quality of life even after surgical
      treatment. In addition to identifying a large number of genes required for palate
      development, recent studies have begun to unravel the extensive cross-regulation
      of multiple signaling pathways, including Sonic hedgehog, bone morphogenetic
      protein, fibroblast growth factor, transforming growth factor beta, and Wnt
      signaling, and multiple transcription factors during palatal shelf growth and
      patterning. Multiple studies also provide new insights into the gene regulatory
      networks and/or dynamic cellular processes underlying palatal shelf elevation,
      adhesion, and fusion. Here we summarize major recent advances and integrate the
      genes and molecular pathways with the cellular and morphogenetic processes of
      palatal shelf growth, patterning, elevation, adhesion, and fusion.

PMID- 28745930
TI  - What Does the Eggshell Cuticle Do? A Functional Comparison of Avian Eggshell
      Cuticles.
AB  - The avian eggshell is a highly ordered structure with several layers (mammillae,
      palisades, and vertical crystal layer) composed of calcium carbonate (~96%) and
      minerals within an organic matrix. The cuticle is a noncalcified layer that
      covers the eggshells of most bird species. Eggshells are multifunctional
      structures that have evolved in response to diverse embryonic requirements and
      challenges, including protection from microbial infection, nest flooding, and
      exposure to solar radiation. However, experimental evidence for these functions
      across diverse taxa is currently limited. Here we investigated the effects of
      nanosphere cuticles on (1) bacterial attachment and transshell penetration, (2)
      eggshell wettability, (3) water vapor conductance, and (4) regulation of
      ultraviolet (UV) reflectance in seven ground-nesting bird species. We found
      considerable interspecific variation in ultrastructure and chemical composition
      of cuticles. Experimental removal of the cuticle confirmed that all nanospheres
      were highly effective at decreasing attachment of bacteria to shell surfaces and
      at preventing bacterial penetration. Cuticles also greatly decreased the amount
      of UV reflected by eggshells. In species with particularly small nanospheres, gas
      exchange was reduced by the presence of cuticle. Our results support the
      hypothesis that microbes and solar UV radiation can cause strong selection on
      bird eggs but also show that we need a greater understanding about the effects of
      specific nesting conditions (e.g., hydric and gaseous milieu) on embryo well
      being and eggshell structure variation.

PMID- 28745931
TI  - Prospect for immune checkpoint blockade: dynamic and comprehensive monitorings
      pave the way.
AB  - Immune checkpoint blockade, which releases the brake of the immune system to
      enhance anticancer immune response, stands out in the cancer immunotherapy field
      due to their remarkable and long-lasting effect. However, the overall response
      rate for currently approved immune checkpoint inhibitors is only about 10-40%. We
      have summarized three major components, which are the presence of checkpoints,
      the immune-activation mechanism and the immune-inhibitory mechanism, containing
      six factors to describe the cancer-immune interaction dynamically and
      comprehensively, which shed light on promising biomarkers in immune checkpoint
      therapy.

PMID- 28745932
TI  - Genetic deletion of microglial Panx1 attenuates morphine withdrawal, but not
      analgesic tolerance or hyperalgesia in mice.
AB  - Opioids are among the most powerful analgesics for managing pain, yet their
      repeated use can lead to the development of severe adverse effects. In a recent
      study, we identified the microglial pannexin-1 channel (Panx1) as a critical
      substrate for opioid withdrawal. Here, we investigated whether microglial Panx1
      contributes to opioid-induced hyperalgesia (OIH) and opioid analgesic tolerance
      using mice with a tamoxifen-inducible deletion of microglial Panx1. We determined
      that escalating doses of morphine resulted in thermal pain hypersensitivity in
      both Panx1-expressing and microglial Panx1-deficient mice. In microglial Panx1
      deficient mice, we also found that acute morphine antinociception remained
      intact, and repeated morphine treatment at a constant dose resulted in a
      progressive decline in morphine antinociception and a reduction in morphine
      potency. This reduction in morphine antinociceptive potency was indistinguishable
      from that observed in Panx1-expressing mice. Notably, morphine tolerant animals
      displayed increased spinal microglial reactivity, but no change of microglial
      Panx1 expression. Collectively, our findings indicate microglial Panx1
      differentially contributes to opioid withdrawal, but not the development of
      opioid-induced hyperalgesia or tolerance.

PMID- 28745933
TI  - Does eIF3 promote reinitiation after translation of short upstream ORFs also in
      mammalian cells?
AB  - Reinitiation after translation of short upstream ORFs (uORFs) represents one of
      the means of regulation of gene expression on the mRNA-specific level in response
      to changing environmental conditions. Over the years it has been shown-mainly in
      budding yeast-that its efficiency depends on cis-acting features occurring in
      sequences flanking reinitiation-permissive uORFs, the nature of their coding
      sequences, as well as protein factors acting in trans. We earlier demonstrated
      that the first two uORFs from the reinitiation-regulated yeast GCN4 mRNA leader
      carry specific structural elements in their 5' sequences that interact with the
      translation initiation factor eIF3 to prevent full ribosomal recycling post their
      translation. Actually, this interaction turned out to be instrumental in
      stabilizing the mRNA.40S post-termination complex, which is thus capable to
      eventually resume scanning and reinitiate on the next AUG start site downstream.
      Recently, we also provided important in vivo evidence strongly supporting the
      long-standing idea that to stimulate reinitiation, eIF3 has to remain bound to
      ribosomes elongating these uORFs until their stop codon has been reached. Here we
      examined the importance of eIF3 and sequences flanking uORF1 of the human
      functional homolog of yeast GCN4, ATF4, in stimulation of efficient reinitiation.
      We revealed that the molecular basis of the reinitiation mechanism is conserved
      between yeasts and humans.

PMID- 28745935
TI  - Use of Electronic Health Record Data for Quality Reporting.

PMID- 28745934
TI  - Spinal Cord Injury Clinical Registries: Improving Care across the SCI Care
      Continuum by Identifying Knowledge Gaps.
AB  - Timely access and ongoing delivery of care and therapeutic interventions is
      needed to maximize recovery and function after traumatic spinal cord injury
      (tSCI). To ensure these decisions are evidence-based, access to consistent,
      reliable, and valid sources of clinical data is required. The Access to Care and
      Timing Model used data from the Rick Hansen SCI Registry (RHSCIR) to generate a
      simulation of healthcare delivery for persons after tSCI and to test scenarios
      aimed at improving outcomes and reducing the economic burden of SCI. Through
      model development, we identified knowledge gaps and challenges in the literature
      and current health outcomes data collection throughout the continuum of SCI care.
      The objectives of this article were to describe these gaps and to provide
      recommendations for bridging them. Accurate information on injury severity after
      tSCI was hindered by difficulties in conducting neurological assessments and
      classifications of SCI (e.g., timing), variations in reporting, and the lack of a
      validated SCI-specific measure of associated injuries. There was also limited
      availability of reliable data on patient factors such as multi-morbidity and
      patient-reported measures. Knowledge gaps related to structures (e.g., protocols)
      and processes (e.g., costs) at each phase of care have prevented comprehensive
      evaluation of system performance. Addressing these knowledge gaps will enhance
      comparative and cost-effectiveness evaluations to inform decision-making and
      standards of care. Recommendations to do so were: standardize data element
      collection and facilitate database linkages, validate and adopt more outcome
      measures for SCI, and increase opportunities for collaborations with stakeholders
      from diverse backgrounds.

PMID- 28745937
TI  - Improved Survival with Bevacizumab in Advanced Cervical Cancer.

PMID- 28745936
TI  - 5-hydroxymethylcytosine in DNA repair: A new player or a red herring?
AB  - Active DNA demethylation performed by ten-eleven translocation (TET) enzymes
      produces 5-hydroxymethylcytosines, 5-formylcytosines, and 5-carboxylcytosines.
      Recent observations suggest that 5-hydroxymethylcytosine is a stable epigenetic
      mark rather than merely an intermediate of DNA demethylation. However, the clear
      functional role of this new epigenetic player is elusive. The contribution of 5
      hydroxymethylation to DNA repair is being discussed currently. Recently, Jiang
      and colleagues have demonstrated that DNA damage response-activated ATR kinase
      phosphorylates TET3 in mammalian cells and promotes DNA demethylation and 5
      hydroxymethylcytosine accumulation. Moreover, TET3 catalytic activity is
      important for proper DNA repair and cell survival. Here, we discuss recent
      studies on the potential role of 5-hydroxymethylation in DNA repair and genome
      integrity maintenance.

PMID- 28745938
TI  - Inhibition of NEDD4 inhibits cell growth and invasion and induces cell apoptosis
      in bladder cancer cells.
AB  - The neural precursor cell expressed developmentally downregulated protein 4
      (NEDD4) plays a pivotal oncogenic role in various types of human cancers.
      However, the function of NEDD4 in bladder cancer has not been fully investigated.
      In the present study, we aim to explore whether NEDD4 governs cell proliferation,
      apoptosis, migration, and invasion in bladder cancer cells. Our results showed
      that downregulation of NEDD4 suppressed cell proliferation in bladder cancer
      cells. Moreover, we found that inhibition of NEDD4 significantly induced cell
      apoptosis. Furthermore, downregulation of NEDD4 retarded cell migration and
      invasion. Notably, overexpression of NEDD4 enhanced cell growth and inhibited
      apoptosis. Consistently, upregulation of NEDD4 promoted cell migration and
      invasion in bladder cancer cells. Mechanically, our Western blotting results
      revealed that downregulation of NEDD4 activated PTEN and inhibited Notch-1
      expression, whereas upregulation of NEDD4 reduced PTEN level and increased Notch
      1 level in bladder cancer cells. Our findings indicated that NEDD4 exerts its
      oncogenic function partly due to regulation of PTEN and Notch-1 in bladder cancer
      cells. These results further revealed that targeting NEDD4 could be a useful
      approach for the treatment of bladder cancer.

PMID- 28745939
TI  - Reduced Pineal Volume in Alzheimer Disease: A Retrospective Cross-sectional MR
      Imaging Study.
AB  - Purpose To evaluate pineal volume in patients with Alzheimer disease (AD),
      patients with mild cognitive impairment (MCI), and healthy control subjects and
      to correlate the findings with results of cognitive testing and brain parenchymal
      volumes. Materials and Methods The ethics committee approved this retrospective
      study. The participants included 63 patients with AD, 33 patients with MCI, and
      24 healthy control subjects. There were 36 men and 84 women, with a mean age (+/
      standard deviation) of 76.7 years +/- 7.6. The pineal gland volume and pineal
      parenchymal volume were measured by using three-dimensional volumetric magnetic
      resonance imaging (T1-weighted magnetization-prepared rapid gradient-echo
      sequence; spatial resolution, 0.9 * 0.98 * 0.98 mm). With age and total
      intracranial volume as covariates, analysis of covariance with the Bonferroni
      post hoc test was performed to compare the pineal volume among the AD, MCI, and
      control groups. Multiple regression analyses were used to identify predictor
      variables associated with pineal volume. Results The mean pineal gland volume in
      patients with AD (72.3 mm3 +/- 5.4; 95% confidence interval [CI]: 61.5 mm3, 83.1
      mm3) was significantly smaller than that in control subjects (102.1 mm3 +/- 9.0;
      95% CI: 84.4 mm3, 119.9 mm3) (P = .019). The mean pineal parenchymal volume in
      patients with AD (63.8 mm3 +/- 4.2; 95% CI: 55.4 mm3, 72.1 mm3) was significantly
      smaller than that in patients with MCI (81.7 mm3 +/- 5.8; 95% CI: 70.3 mm3, 93.1
      mm3; P = .044) and control subjects (89.1 mm3 +/- 6.9; 95% CI: 75.4 mm3, 102.9
      mm3; P = .009). Multiple regression analyses demonstrated that the Mini-Mental
      State Examination score and total intracranial volume were significant
      independent predictors of both pineal gland volume and pineal parenchymal volume
      (P < .001). Conclusion Pineal volume reduction showed correlation with cognitive
      decline and thus might be useful to predict cognitive decline in patients with
      AD. (c) RSNA, 2017.

PMID- 28745940
TI  - Intravenous Corticosteroid Premedication Administered 5 Hours before CT Compared
      with a Traditional 13-Hour Oral Regimen.
AB  - Purpose To determine if the allergic-like breakthrough reaction rate of
      intravenous corticosteroid prophylaxis administered 5 hours before contrast
      material-enhanced computed tomography (CT) is noninferior to that of a
      traditional 13-hour oral regimen. Materials and Methods Institutional review
      board approval was obtained and informed consent waived for this retrospective
      noninferiority cohort study. Subjects (n = 202) who completed an accelerated 5
      hour intravenous corticosteroid premedication regimen before low-osmolality
      contrast-enhanced CT for a prior allergic-like or unknown-type reaction to iodine
      based contrast material from June 1, 2008, to June 30, 2016, were identified. The
      breakthrough reaction rate was compared by using the Farrington and Manning
      noninferiority likelihood score to test subjects premedicated with a traditional
      13-hour oral regimen (2.1% [13 of 626]). All subjects were premedicated for a
      prior allergic-like or unknown-type reaction to iodine-based contrast material. A
      noninferiority margin of 4.0% was selected to allow for no more than a clinically
      negligible 6.0% breakthrough reaction rate in the cohort that received 5-hour
      intravenous corticosteroid prophylaxis. Results The breakthrough reaction rate
      for 5-hour intravenous prophylaxis was 2.5% (five of 202 patients; 95% confidence
      interval: 0.8%, 5.7%), which was noninferior to the 2.1% (13 of 626 patients; 95%
      confidence interval: 1.1%, 3.5%) rate for the 13-hour regimen (P = .0181). The
      upper limits of the confidence interval for the difference between the two rates
      was 3.7% (0.4%; 95% confidence interval: -1.6%, 3.7%), which was within the 4.0%
      noninferiority margin. All breakthrough reactions were of equal or lesser
      severity to those of the index reactions (two severe, one moderate, and one mild
      reaction). Conclusion Accelerated intravenous premedication with corticosteroids
      beginning 5 hours before contrast-enhanced CT has a breakthrough reaction rate
      noninferior to that of a 13-hour oral premedication regimen. (c) RSNA, 2017.

PMID- 28745941
TI  - Veterans' Preferences for Remote Management of Chronic Conditions.
AB  - BACKGROUND: The Veterans Health Administration (VA) is investing considerable
      resources into providing remote management care to patients for disease
      prevention and management. Remote management includes online patient portals, e
      mails between patients and providers, follow-up phone calls, and home health
      devices to monitor health status. However, little is known about patients'
      attitudes and preferences for this type of care. This qualitative study was
      conducted to better understand patient preferences for receiving remote care.
      METHODS: Ten focus groups were held comprising 77 patients with hypertension or
      tobacco use history at two VA medical centers. Discussion questions focused on
      experience with current VA remote management efforts and preferences for
      receiving additional care between outpatient visits. RESULTS: Most participants
      were receptive to remote management for referrals, appointment reminders,
      resource information, and motivational and emotional support between visits, but
      described challenges with some technological tools. Participants reported that
      remote management should be personalized and tailored to individual needs. They
      expressed preferences for frequency, scope, continuity of provider, and mode of
      communication between visits. Most participants were open to nonclinicians
      contacting them as long as they had direct connection to their medical team. Some
      participants expressed a preference for a licensed medical professional. All
      groups raised concerns around confidentiality and privacy of healthcare
      information. Female Veterans expressed a desire for gender-sensitive care and an
      interest in complementary and alternative medicine. CONCLUSIONS: The findings and
      specific recommendations from this study can improve existing remote management
      programs and inform the design of future efforts.

PMID- 28745942
TI  - The empirically derived Violence and Aggression Risk Index from the Personality
      Assessment Inventory: Development, validation, and application in general
      psychiatric settings.
AB  - The current study developed a new index of violence risk from scales within the
      Personality Assessment Inventory (PAI). Clinical patients from inpatient and
      outpatient settings completed the PAI along with reports of violence history and
      arrest record. A forward-selection hierarchical logistic regression was employed
      (N = 388) to identify the PAI scales (AGG-P, AGG-A, NON, PAR-H, and ANT-A) that
      could effectively distinguish patients with and without a history of violence.
      These indicators were then aggregated into a single index, labeled the Violence
      and Aggression Risk Index (VARI). The VARI modestly incremented other PAI
      subscales and indices in an independent clinical sample (N = 387). The authors
      discuss how the VARI can be incorporated with the other PAI scales to assess
      violence risk.

PMID- 28745943
TI  - Integrating caring into patient-centered care through interprofessional education
      and ethics: The Caring Project.
AB  - In an era of health care that is driven by biological and technical advances,
      there is a need to safeguard the caring component of care, the humanistic part of
      care. With this in mind, the authors constructed a Patient-Centered Caring model
      consisting of three overlapping constructs: delivering customer service,
      understanding the illness experience, and providing trauma-informed care. These
      practices operate within an interprofessional competency context. The authors
      describe an interprofessional educational project focused on understanding the
      illness experience and providing trauma-informed care to faculty, staff, and
      administrators in an inpatient psychiatric setting. The authors discuss the
      project through a number of ethical lenses that may help explicate the ethics of
      patient-centered care and caring and can be useful in the development of
      interprofessional competence.

PMID- 28745944
TI  - Need to screen for clinical levels of OCD? Four questions are the key.
AB  - The aim of this study was to investigate a new measure, the Wetterneck-Hart OCD
      Screener (WHOS), as a self-report screening tool for obsessive-compulsive
      disorder (OCD). The authors examined relationships between the WHOS and severity
      scores of OCD measures taken via three methods of data collection: online, at OCD
      consumer conferences, and from an intensive, residential OCD program. Severity
      measures included the Yale-Brown Obsessive-Compulsive Scale-Self Report (Y-BOCS
      SR), the Dimensional Obsessive-Compulsive Scale (DOCS), and the Obsessive
      Compulsive Inventory-Revised (OCI-R). A total of 525 participants took the
      measures: 298 from online websites, 100 from OCD conferences, and 127 from a
      residential OCD program. Significant differences were found between the OCD and
      non-OCD groups classified by the WHOS for each of the OCD severity measures. The
      authors conclude that the WHOS is useful in predicting the presence of clinically
      severe OCD symptoms and could be employed in clinical and research endeavors.

PMID- 28745945
TI  - Elena: A case of dissociative identity disorder from the 1920s.
AB  - In 1930, Italian psychiatrist Giovanni Enrico Morselli described the history,
      diagnosis, and treatment of his patient Elena. The case of Elena has been
      considered in literature as one of the most remarkable cases of multiple
      personality ever published. In fact, before treatment, Elena showed alternating
      French- and Italian-speaking personalities, with the Italian personality knowing
      nothing of her French counterparts. After a difficult treatment involving
      recovered memories of incestuous attacks by her father, which were proven to be
      true, Elena fully recovered from her symptoms. In this article, the author
      presents details of the case that were not available in the international
      literature before. He also discusses Elena's psychological and somatoform
      symptoms according to a contemporary perspective on the relationally traumatic
      origins of dissociation and dissociative identity disorder.

PMID- 28745946
TI  - Mentalization-based treatment for borderline personality disorder in adults and
      adolescents: For whom, when, and how?
AB  - Borderline personality disorder (BPD) is common in clinical practice.
      Psychotherapy is the treatment of choice, and mentalization-based treatment (MBT)
      is one of the empirically supported treatments that are currently available. For
      adults, two variants of MBT (MBT day hospital [MBT-DH] and MBT intensive
      outpatient [MBT-IOP]) have been developed and empirically evaluated. The authors
      review research on the development, efficacy, and implementation of MBT. In
      conclusion, the authors focus on the implementation of treatment programs for BPD
      patients. Although there are now different effective treatments, their
      implementation in routine clinical practice has proven to be much more complex
      than initially thought. In addition, treatments such as MBT are multimodal and
      long term. Both societal pressures to increase the cost-effectiveness of
      treatments and new theoretical insights into the role of social learning and
      salutogenesis in the development of BPD force a reconsideration of some
      assumptions concerning the nature of treatment for individuals with BPD.

PMID- 28745947
TI  - Identity Narrative Density: Preliminary findings from scoring emotional valence
      of autobiographical events.
AB  - Autobiographical Memory is a form of declarative episodic memory known to have a
      significant role in identity, self-regulation, and socialization. Conceivably, it
      may also influence outcome of psychopathology. This is a preliminary report in
      which the authors are proposing the notion of Identity Narrative (IdN), a set of
      implicit memories acquired throughout life and consolidated according to a
      gradient of emotional valence. IdN may constitute an implicit scaffolding for
      autobiographical memory. Identity Narrative Density (IND) is a score of emotional
      valence referring to life events that contribute to the construction of an IdN.
      The authors are proposing an equation of IND that provides a quantitative
      assessment of an individual's emotional life experiences and possible resilience
      in the face of trauma and adversities of life.

PMID- 28745948
TI  - The coconstruction of interpersonal recognition in the clinical dialogue of the
      diagnostic process: A multilevel analysis of the verbal content and vocal
      nonverbal dimension.
AB  - The present study is an empirical evaluation of a clinical setting from a
      particular point of view, able to integrate the vocal dimension-used in different
      fields of psychology as an indicator of rational phenomena-with the linguistic
      dimension of contents. Starting from the "interpersonal recognition" extracted
      from the contents of the verbatim transcripts of some diagnostic processes using
      the Strumento di Valutazione del Riconoscimento Interpersonale (Evaluation Tool
      for Interpersonal Recognition), the variation of vocal parameters both in the
      clinician and in the patient were analyzed. The goal consists in identifying
      possible nonverbal vocal micro indicators used in the dyadic process of
      interpersonal recognition. Specific and bidimensional nonverbal vocal patterns
      and strategies are hypothetically matched with different efficacy levels of
      recognition, both for the clinician and the patient.

PMID- 28745949
TI  - Short-term psychodynamic therapy for obsessive-compulsive disorder: A manual
      guided approach to treating the "inhibited rebel".
AB  - Obsessive-compulsive disorder (OCD) is a chronic disabling disorder characterized
      by recurrent obsessions and uncontrolled compulsions. Recent research on anxiety
      disorders suggests that manual-guided short-term psychodynamic therapy (STPP) may
      be a promising approach. Building on this, a model of STPP for OCD was developed
      based on Luborsky's supportive-expressive (SE) therapy. Treatment consists of 12
      modules, which include the characteristic elements of SE therapy, that is, a
      focus on the Core Conflictual Relationship Theme (CCRT) associated with OCD
      symptoms and on establishing a secure alliance. Disorder-specific treatment
      elements were integrated, including addressing ambivalence, differentiating
      between thinking and acting, mitigating the superego, addressing existential
      issues, and, last but not least, implementing Freud's original recommendation to
      induce OCD patients to face the feared situation and to use the aroused
      experiences to work on the underlying conflict (i.e., CCRT). There are reasons to
      assume that the empirically derived model of STPP described here may be
      beneficial in OCD.

PMID- 28745950
TI  - Declaring Conflict of Interest - Current State of Affairs in the Ophthalmic
      Literature.
AB  - The importance of transparency with financial ties in biomedical research is
      widely recognized, and most peer-reviewed journals require declarations of
      Conflicts of Interest (COI). Nonetheless, variability in the consistency of
      declarations of COI has been sparsely assessed. To assess consistency and rates
      of COI declarations in the ophthalmic literature and the effectiveness of journal
      COI policies. We analyzed consistency and completeness of declaration of COI in
      the ophthalmic literature and compared the levels of completeness to specific
      journal requirements. Six-hundred forty-two peer reviewed articles satisfied the
      inclusion criteria. In 64%, COIs were unreported, in 25% declaration of COI was
      incomplete, and 11% of the articles reviewed had complete declaration of COI. Of
      the 33 journals in which the most frequently published authors' articles
      appeared, 10 required the authors to complete the International Committee of
      Medical Journal Editors (ICMJE) form or an equivalent form, but this did not
      affect the rates of COI declaration. In a random sampling of the most frequently
      published authors in the field of ophthalmology, declaration of COI was low and
      highly inconsistent. Requiring a standardized COI form has no significant effect
      on the rate of accurate COI reporting. Our findings lend support to the growing
      body of literature that shows that journals and editors may need to take a more
      active role in ensuring accurate and consistent COI reporting.

PMID- 28745951
TI  - Preventing bloodstream infection in IV therapy.
AB  - Healthcare-associated infections (HAI) are one cause of preventable harm to
      patients, and are a clinical, political and economic concern. Vascular access,
      via a peripheral or central vascular device, is a routine experience for most
      patients receiving hospital care and is increasingly commonplace in health care
      at home. Because it is so common, ensuring safe vascular access is an essential
      focus for all health professionals. All vascular access procedures are invasive,
      regardless of patient group, therapeutic rationale, the device used, route and
      site of insertion and particular technique. As such there are inherent risks of
      patient harm. Many of these risks are well known and include issues such as
      infiltration, extravasation, phlebitis and pain. Of particular importance is the
      relationship between intravenous (IV) therapy and infection and how best to
      prevent HAI, specifically in relation to IV therapy, bloodstream infections,
      catheter-related bloodstream infections and central-line associated blood stream
      infections. This article considers the interrelationship between IV therapy
      bloodstream infections and measures to prevent HAI and summarises key principles
      in this ongoing endeavour.

PMID- 28745952
TI  - Getting hand hygiene right.

PMID- 28745953
TI  - Respiratory challenges.

PMID- 28745955
TI  - Runner up 2017.

PMID- 28745954
TI  - Assessing the impact of a respiratory diagnosis on smoking cessation.
AB  - The aim of this study was to assess the impact of respiratory diagnoses on
      smoking cessation. A total of 229 current and former smokers, with and without
      respiratory diagnoses completed an anonymous online questionnaire assessing how
      their smoking habit changed when diagnosed with various respiratory conditions.
      Among all participants the most common reason for quitting smoking was to reduce
      the risk of health problems in general. In those with a chronic respiratory
      diagnosis, this was their most common reason for quitting. Motivation to quit
      smoking, scored by participants on a scale of 0-10, increased at the time of
      diagnosis then further increased after diagnosis of a chronic respiratory
      condition but declined after diagnosis of an acute respiratory condition. The
      research had a small sample size so further research is required. However,
      important themes are highlighted with the potential to influence clinical
      practice. All clinicians should receive training to promote cessation at the time
      of diagnosing respiratory conditions.

PMID- 28745956
TI  - New standards and framework will map out the future of nursing.
AB  - Duncan Hamilton, Second Year Student, Adult Nursing, University of Surrey, shares
      what he thinks is missing from the Nursing and Midwifery Council's draft
      Standards of Proficiency and Education Framework.

PMID- 28745957
TI  - Understanding the challenges to vascular access in an ageing population.
AB  - At the beginning of the 21st century, one in five of UK residents can expect to
      see their 100th birthday and one in four people are aged 60 years or older. The
      UK has an ageing population. With older age comes an increasing variety of
      comorbidities that have an impact not only on an individual's quality of life but
      also on healthcare resources. Older people account for a rapidly rising cohort of
      individuals admitted to hospital, often with complex needs, and this can require
      achieving venous access. Venepuncture and cannulation are the most commonly
      performed invasive procedures in health care today. This article aims to increase
      awareness of vascular access challenges in older patients so the potential for
      complications relating to venepuncture, cannulation and infusion therapy can be
      minimised, thereby improving their overall quality of care. The article will look
      at the healthcare challenges facing the older population, and the importance of a
      holistic approach to assess their vascular access needs to deliver optimum care.

PMID- 28745958
TI  - Considering the uncompliant patient: a four-step approach.

PMID- 28745959
TI  - Closed arterial lab sampling devices: a study of compliance and best practice.
AB  - As the quality of patient care continues to improve, nursing professionals are
      continuously tasked with researching, implementing, and evaluating best
      practices. The practice of obtaining blood samples from paediatric patients,
      using a conventional three-way stopcock method, has been associated with
      peripheral arterial catheter intraluminal contamination and catheter-related
      bloodstream infections. A paediatric cardiac intensive care unit (PCICU), in a
      large medical centre in the USA, set an objective to mitigate the risk of
      possible contamination by implementing the use of closed arterial lab sampling
      devices. The project extensively reviewed comparative literature of studies
      between conventional three-way stopcock methods and closed arterial lab sampling
      devices. Furthermore, it successfully implemented the recommended best practice
      with sustained compliance. This article discusses appraising current literature,
      translating into practice, and evaluating compliance throughout the PCICU over a
      2-year period.

PMID- 28745960
TI  - Meeting modern students' needs: the use of social media in nurse education.

PMID- 28745961
TI  - The benefits of interprofessional education 10 years on.
AB  - Interprofessional education (IPE) was first conceived in 1973 by a World Health
      Organization (WHO) expert group in Geneva. WHO member states were then charged
      with implementing medical education IPE pilot projects and from then to today
      there has a been a rapid proliferation in the number of publications on the
      subject. IPE has generated research into its use, conferences specific to IPE,
      organisations dedicated to it and policy championing it. The authors question
      whether there has been any major shift in the silos in which different
      professions might be working. The authors published an article on the benefits of
      IPE ( Illingworth and Chelvanayagam, 2007 ). Ten years have now passed and many
      changes have been implemented and experienced in health and social care and
      therefore a review of the literature is required. Also, it is 7 years since the
      publication of WHO's report outlining the role of IPE in the preparation of
      health professionals ( WHO, 2010 ) and, increasingly, UK Government policy
      champions collaborative and integrated working. The conclusions from the 2007
      article acknowledged the development of IPE; however, it highlighted the need for
      empirical evidence to demonstrate the effectiveness of IPE in service user and
      carer outcomes. This article will explore whether IPE has achieved the benefits
      discussed in the previous article and what developments have occurred since it
      was published.

PMID- 28745962
TI  - Innovation Award Runner up 2017.

PMID- 28745963
TI  - The human cost of budget cuts.

PMID- 28745964
TI  - Introduction of a nurse-led intravitreal injection service in ophthalmology.
AB  - Anti-VEGF (anti-vascular endothelial growth factor) agents are useful for a
      variety of previously untreatable eye conditions; indications for their use are
      increasing. As this treatment evolved from cutting-edge to mainstream NHS
      practice, it resulted in a significant increase in appointments for intravitreal
      (IVT) injections, clinical assessment and follow-up, and hence an increasing
      challenge to ensure its timely availability to all who needed it. In addressing
      that challenge, NHS Lothian successfully initiated an advanced nurse practitioner
      IVT service in addition to its medical IVT service, which has increased its
      capacity to provide the requisite high-quality care to this patient group.

PMID- 28745965
TI  - From staff nurse to nurse consultant: Spiritual care part 4: Christianity.
AB  - John Fowler, educational consultant and part-time university chaplain, explores
      the role of clinically based nurses in caring for the spiritual needs of patients
      who are Christians.

PMID- 28745966
TI  - The effects of organisational culture on nurses' perceptions of their work.
AB  - This study aimed to analyse the relationship between the organisational culture
      and feelings of pleasure and suffering among working nursing professionals. This
      was a cross-sectional correlational study conducted in a tertiary hospital with
      214 nursing staff over 3 months using three instruments: professional
      characterisation, the Brazilian Instrument for Assessment of Organisational
      Culture, and the Scale of Pleasure and Suffering at Work. The analysis included
      descriptive statistics and the Spearman correlation test. The external
      integration practice was the domain most frequently found in the organisational
      culture and the feeling of pleasure-gratification predominated among the workers.
      Values of cooperative professionalism and wellbeing, and practices of external
      integration and relationship promotion, were related to increased pleasure and
      decreased suffering at work. These aspects depend on the organisational culture
      of the institution. Investigating organisational culture facilitates the
      understanding of potential collective coping strategies and the organisational
      changes that favour good mental health in nurses.

PMID- 28745967
TI  - Improving patient safety and healthcare quality: examples of good practice.
AB  - John Tingle, Reader in Health Law at Nottingham Trent University, discusses a
      recent report by the Care Quality Commission that showcases eight NHS trusts that
      have improved their patient safety and healthcare quality.

PMID- 28745968
TI  - A guide to vascular access in haemodialysis patients.

PMID- 28745969
TI  - Creating workforce transformation.
AB  - Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, looks at
      opportunities for continuing professional development, which is key for both
      recruitment and retention.

PMID- 28745970
TI  - Are health visiting and school nursing in crisis?
AB  - Emeritus Professor Alan Glasper, from the University of Southampton, discusses a
      report from the Royal College of Nursing on the significant decline in the number
      of school nurses and health visitors.

PMID- 28745971
TI  - Sexuality and the older woman.
AB  - Sexual health is a key public health issue. The older woman faces a number of
      changes to her sexual health, wellbeing and sexuality. These changes result in
      many older women having to adapt to a series of complex transitions that can be
      challenging. This article aims to identify and explore some of these changes and
      how they can have a significant impact on women's quality of life. Nurses play an
      important role in assessing and helping women to manage normal and pathological
      age-related changes in order to improve the sexual health of older women and
      ensure they receive the advice and support needed at this stage of their life.

PMID- 28745972
TI  - A 20-Year Follow-up After First-Generation Autologous Chondrocyte Implantation.
AB  - BACKGROUND: Treating articular cartilage defects is a demanding problem. Although
      several studies have reported durable and improved clinical outcomes after
      autologous chondrocyte implantation (ACI) over a long-term period, there is no
      report with over 20 years' follow-up. PURPOSE: To evaluate clinical outcomes
      after first-generation ACI for the treatment of knees with disabling, large
      single and multiple cartilage defects for which patients wished to avoid
      prosthetic arthroplasty, with a minimum of 20 years' follow-up. STUDY DESIGN:
      Case series; Level of evidence, 4. METHODS: The authors reviewed prospectively
      collected data from 23 patients (24 knees; mean age, 35.4 years [range, 13-52
      years]) undergoing ACI for the treatment of symptomatic, full-thickness articular
      cartilage lesions. A mean of 2.1 lesions per knee were treated over a mean total
      surface area of 11.8 cm2 (range, 2.4-30.5 cm2) per knee. Kaplan-Meier survival
      analysis and functional outcome scores, including the modified Cincinnati Knee
      Rating System, Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC), and Short Form-36 (SF-36), were used. Patients also self-reported an
      improvement in pain with a visual analog scale and a satisfaction survey.
      RESULTS: The 20-year survival rate was 63% (95% CI, 40%-78%). The evaluation of
      the 15 knees with retained grafts demonstrated that all clinical scores except
      the WOMAC subscore for stiffness and SF-36 mental component summary score
      improved significantly and were sustained to 20 years postoperatively. Ninety
      three percent of these patients rated knee-specific outcomes as good or
      excellent. The outcomes for 9 of 24 knees were considered failures, including 5
      undergoing revision ACI and 4 being converted to arthroplasty at a mean of 1.7
      and 5.9 years, respectively. Only 1 of 5 knees that underwent revision ACI was
      converted to arthroplasty at 1.9 years after the index surgery, and the other 4
      patients were able to maintain their biological knee. Overall, 20 years later,
      79% of patients maintained their native knee, for which they initially sought
      treatment, and were satisfied when evaluated. CONCLUSION: First-generation ACI
      provided satisfactory survival rates and significant clinical improvements over a
      20-year follow-up, which offers an important standard for comparison with newer
      generation ACI technologies of the future.

PMID- 28745973
TI  - Working with Families Affected by Mental Distress: Stakeholders' Perceptions of
      Mental Health Nurses Educational Needs.
AB  - Family and informal caregivers provide a substantial amount of care and support
      to people who experience mental health problems. The aim of this study was to
      explore mental health nurses', students' and service users' perceptions of the
      knowledge, skills and attitudes that are required by mental health nurses to work
      with families and carers using a qualitative methodology. Three themes emerged
      from the data: Knowledge of the family and how mental distress affects the
      family; working with the family - support and education; and valuing the role of
      the family. The three themes demonstrate the complexity of preparing mental
      health nurses to work with families and carers, and the article offers
      recommendations about how this might be achieved.

PMID- 28745974
TI  - Role of Total Ankle Arthroplasty in Stiff Ankles.
AB  - BACKGROUND: The decision tree for the operative treatment of end-stage ankle
      arthritis involves either ankle arthrodesis (AA) or total ankle arthroplasty
      (TAA). Although both have documented success providing diminished pain, improved
      patient-centered outcomes, and improved objective measures of function,
      arthroplasty is unique in its ability to preserve motion at the tibiotalar joint.
      Arthroplasty procedures are normally thought of as a motion-sparing surgery
      rather than a motion-producing procedure, which may limit its success in patients
      with stiff ankles. Our hypothesis was that there would be improvements in
      parameters of gait even in patients with a low degree of preoperative total
      sagittal range of motion. METHODS: A retrospective review was conducted on
      patients who underwent total ankle arthroplasty with greater than 1-year follow
      up. Seventy-six patients were available who underwent isolated TAA for end-stage
      ankle arthritis with greater than 1-year follow-up. Patient demographics and
      preoperative and postoperative gait analyses were evaluated. Using a linear
      regression model, the effect sizes for the variables of age, gender, BMI,
      preoperative diagnosis, and preoperative total sagittal range of motion were
      calculated. Multivariate analysis was used to determine the influence each
      individual variable had on the many parameters of preoperative gait,
      postoperative gait, and change in gait after surgery. A post hoc analysis was
      conducted in which patients were divided into 4 quartiles according to
      preoperative range of motion. A 1-way analysis of variance (ANOVA) was used to
      compare improvement in parameters of gait for the 4 subgroups. RESULTS: Although
      a greater degree of preoperative sagittal range of motion was predictive of
      greater postoperative sagittal range of motion, patients with limited
      preoperative range of motion experienced a greater overall improvement in range
      of motion, and clinically meaningful absolute improvements in range of motion,
      and other parameters of gait. The post hoc analysis demonstrated that patients in
      the lowest quartile of preoperative motion had both statistically and clinically
      significant greater improvements across numerous parameters of gait, although the
      absolute values were lower than in the patients with higher preoperative ROM.
      Age, gender, BMI, and preoperative diagnosis did not correlate with changes in
      parameters of gait after total ankle arthroplasty. CONCLUSION: Preoperative range
      of motion was predictive of overall postoperative gait function. On one hand, a
      low preoperative range of motion resulted in a lower absolute postoperative
      function. On the other hand, patients with stiff ankles preoperatively had a
      statistically and clinically greater improvement in function as measured by
      multiple parameters of gait. This suggests that total ankle arthroplasty can
      offer clinically meaningful improvement in gait function and should be considered
      for patients with end-stage tibiotalar arthritis even in the setting of limited
      sagittal range of motion. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 28745975
TI  - Identification of Chemical Compounds That Inhibit the Function of Histidyl-tRNA
      Synthetase from Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa histidyl-tRNA synthetase (HisRS) was selected as a target
      for antibiotic drug development. The HisRS protein was overexpressed in
      Escherichia coli and kinetically evaluated. The KM values for interaction of
      HisRS with its three substrates, histidine, ATP, and tRNAHis, were 37.6, 298.5,
      and 1.5 MUM, while the turnover numbers were 8.32, 16.8, and 0.57 s-1,
      respectively. A robust screening assay was developed, and 800 natural products
      and 890 synthetic compounds were screened for inhibition of activity. Fifteen
      compounds with inhibitory activity were identified, and the minimum inhibitory
      concentration (MIC) was determined for each against a panel of nine pathogenic
      bacteria. Each compound exhibited broad-spectrum activity. Based on structural
      similarity and MIC results, four compounds, BT02C02, BT02D04, BT08E04, and
      BT09C11, were selected for additional analysis. These compounds inhibited the
      activity of HisRS with IC50 values of 4.4, 9.7, 14.1, and 11.3 uM, respectively.
      Time-kill studies indicated a bacteriostatic mode of inhibition for each
      compound. BT02D04 and BT08E04 were noncompetitive with both histidine and ATP,
      BT02C02 was competitive with histidine but noncompetitive with ATP, and BT09C11
      was uncompetitive with histidine and noncompetitive with ATP. These compounds
      were not observed to be toxic to human cell cultures.

PMID- 28745976
TI  - New Approaches to Difficult Drug Targets: The Phosphatase Story.
AB  - The drug discovery landscape is littered with promising therapeutic targets that
      have been abandoned because of insufficient validation, historical screening
      failures, and inferior chemotypes. Molecular targets once labeled as
      "undruggable" or "intractable" are now being more carefully interrogated, and
      while they remain challenging, many target classes are appearing more
      approachable. Protein tyrosine phosphatases represent an excellent example of a
      category of molecular targets that have emerged as druggable, with several small
      molecules and antibodies recently becoming available for further development. In
      this review, we examine some of the diseases that are associated with protein
      tyrosine phosphatase dysfunction and use some prototype contemporary strategies
      to illustrate approaches that are being used to identify small molecules
      targeting this enzyme class.

PMID- 28745978
TI  - Improved Outcomes in Men with Advanced Prostate Cancer.

PMID- 28745977
TI  - Zap70 and downstream RanBP2 are required for the exact timing of the meiotic cell
      cycle in oocytes.
AB  - In previous studies, we observed that Zeta-chain-associated protein kinase 70
      (Zap70) regulates spindle assembly and chromosome alignment in mouse oocyte and
      that Ran binding protein 2 (RanBP2) is a highly associated gene with Zap70 based
      on a microarray analysis. Because RanBP2 is related to nuclear envelope breakdown
      (NEBD) during mitosis, the aim of the present study was to elucidate the
      molecular mechanism of Zap70 with respect to RanBP2 in the germinal vesicle
      breakdown (GVBD) of oocytes. Results indicated that RanBP2 expression was
      regulated by Zap70 and that depletion of RanBP2 using RanBP2 RNAi manifested
      comparable phenotypes to those observed in Zap70 RNAi-treated oocytes, which
      presented faster processing of GVBD. Additionally, Zap70 RNAi-treated oocytes
      showed faster meiotic resumption with premature activation of maturation
      promoting factor (MPF), premature division of chromosomes at approximately 6-8 h
      and more rapid degradation of securin. In conclusion, we report that Zap70 is a
      crucial factor for controlling the exact timing of meiotic progression in mouse
      oocytes.

PMID- 28745980
TI  - Data Authorship as an Incentive to Data Sharing.

PMID- 28745981
TI  - Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction.

PMID- 28745982
TI  - Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction.

PMID- 28745983
TI  - Physical Abuse of Children.

PMID- 28745984
TI  - Physical Abuse of Children.

PMID- 28745985
TI  - Acral Melanoma and Mechanical Stress on the Plantar Surface of the Foot.

PMID- 28745986
TI  - Ventilation in Extremely Preterm Infants and Respiratory Function at 8 Years.
AB  - BACKGROUND: Assisted ventilation for extremely preterm infants (<28 weeks of
      gestation) has become less invasive, but it is unclear whether such developments
      in care are associated with improvements in short-term or long-term lung
      function. We compared changes over time in the use of assisted ventilation and
      oxygen therapy during the newborn period and in lung function at 8 years of age
      in children whose birth was extremely premature. METHODS: We conducted
      longitudinal follow-up of all survivors of extremely preterm birth who were born
      in Victoria, Australia, in three periods - the years 1991 and 1992 (225 infants),
      1997 (151 infants), and 2005 (170 infants). Perinatal data were collected
      prospectively, including data on the duration and type of assisted ventilation
      provided, the duration of oxygen therapy, and oxygen requirements at 36 weeks of
      age. Expiratory airflow was measured at 8 years of age, and values were converted
      to z scores for age, height, ethnic group, and sex. RESULTS: The duration of
      assisted ventilation rose substantially over time, with a large increase in the
      duration of nasal continuous positive airway pressure. Despite the increase in
      the use of less invasive ventilation over time, the duration of oxygen therapy
      and the rate of oxygen dependence at 36 weeks rose, and airflows at 8 years of
      age were worse in 2005 than in earlier periods. For instance, for 2005 versus
      1991-1992, the mean difference in the z scores for the ratio of forced expiratory
      volume in 1 second to forced vital capacity was -0.75 (95% confidence interval
      [CI], -1.07 to -0.44; P<0.001), and for 2005 versus 1997 the mean difference was 
      0.53 (95% CI, -0.86 to -0.19; P=0.002). CONCLUSIONS: Despite substantial
      increases in the use of less invasive ventilation after birth, there was no
      significant decline in oxygen dependence at 36 weeks and no significant
      improvement in lung function in childhood over time. (Funded by the National
      Health and Medical Research Council of Australia and the Victorian Government's
      Operational Infrastructure Support Program.).

PMID- 28745988
TI  - More on Intralymphatic Injection of Autoantigen in Type 1 Diabetes.

PMID- 28745987
TI  - Mobile DNA in Health and Disease.

PMID- 28745989
TI  - The Price of Crossing the Border for Medications.

PMID- 28745990
TI  - Use of Pressure Transducers.

PMID- 28745991
TI  - Use of Pressure Transducers.

PMID- 28745992
TI  - Cholelithiasis.

PMID- 28745993
TI  - All That Wheezes...

PMID- 28745994
TI  - Case 23-2017. A 9-Day-Old Girl with Vomiting, Acidosis, and Azotemia.

PMID- 28745995
TI  - Intralymphatic Injection of Autoantigen in Type 1 Diabetes.

PMID- 28745996
TI  - Nystagmus from Wernicke's Encephalopathy.

PMID- 28745997
TI  - Noninvasive Ventilation in the Premature Newborn - Is Less Always More?

PMID- 28745998
TI  - Giant-Cell Arteritis - More Ecstasy, Less Agony.

PMID- 28745999
TI  - Trial of Tocilizumab in Giant-Cell Arteritis.
AB  - BACKGROUND: Giant-cell arteritis commonly relapses when glucocorticoids are
      tapered, and the prolonged use of glucocorticoids is associated with side
      effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on
      the rates of relapse during glucocorticoid tapering was studied in patients with
      giant-cell arteritis. METHODS: In this 1-year trial, we randomly assigned 251
      patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of
      162 mg) weekly or every other week, combined with a 26-week prednisone taper, or
      placebo combined with a prednisone taper over a period of either 26 weeks or 52
      weeks. The primary outcome was the rate of sustained glucocorticoid-free
      remission at week 52 in each tocilizumab group as compared with the rate in the
      placebo group that underwent the 26-week prednisone taper. The key secondary
      outcome was the rate of remission in each tocilizumab group as compared with the
      placebo group that underwent the 52-week prednisone taper. Dosing of prednisone
      and safety were also assessed. RESULTS: Sustained remission at week 52 occurred
      in 56% of the patients treated with tocilizumab weekly and in 53% of those
      treated with tocilizumab every other week, as compared with 14% of those in the
      placebo group that underwent the 26-week prednisone taper and 18% of those in the
      placebo group that underwent the 52-week prednisone taper (P<0.001 for the
      comparisons of either active treatment with placebo). The cumulative median
      prednisone dose over the 52-week period was 1862 mg in each tocilizumab group, as
      compared with 3296 mg in the placebo group that underwent the 26-week taper
      (P<0.001 for both comparisons) and 3818 mg in the placebo group that underwent
      the 52-week taper (P<0.001 for both comparisons). Serious adverse events occurred
      in 15% of the patients in the group that received tocilizumab weekly, 14% of
      those in the group that received tocilizumab every other week, 22% of those in
      the placebo group that underwent the 26-week taper, and 25% of those in the
      placebo group that underwent the 52-week taper. Anterior ischemic optic
      neuropathy developed in one patient in the group that received tocilizumab every
      other week. CONCLUSIONS: Tocilizumab, received weekly or every other week,
      combined with a 26-week prednisone taper was superior to either 26-week or 52
      week prednisone tapering plus placebo with regard to sustained glucocorticoid
      free remission in patients with giant-cell arteritis. Longer follow-up is
      necessary to determine the durability of remission and safety of tocilizumab.
      (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01791153 .).

PMID- 28746000
TI  - Using pharmacogenetics to prevent severe adverse reactions to capecitabine.

PMID- 28746002
TI  - Sadomasochism or the Art of Loving: Fromm and Feminist Theory.
AB  - Although the work of Erich Fromm is not usually associated with feminist theory,
      his ideas overall are more consonant with contemporary notions of gender than
      usually recognized. This paper identifies three aspects of Fromm's thought worth
      feminist revisiting. The first relates to Fromm's gender-less use of
      sadomasochism to describe relationships based on dominance and subordination;
      this framework can be applied to sexist dynamics, though not limited to this
      context. Second, Fromm's vision of love as presented in The Art of Loving can be
      seen as kindred with Simone de Beauvoir's critique of romantic love and its
      flaws. Third, and relatedly, Fromm's concerns about the need for recognition as
      well as autonomy are compatible with Jessica Benjamin's notion of mutual
      recognition as developed in her book The Bonds of Love. All told, Frommian and
      feminist thought appear to be more connected than antagonistic.

PMID- 28746003
TI  - Erich Fromm's Involvement With Zen Buddhism: Psychoanalysts and the Spiritual
      Quest in Subsequent Decades.
AB  - The first section of this paper covers Erich Fromm's profound involvement with
      Zen Buddhism, culminating in his co-authoring the book Zen Buddhism and
      Psychoanalysis in 1960. It details why this was a groundbreaking endeavor, as it
      countered the pervasive psychoanalytic denigration of spiritual traditions,
      practices, and experiences. The second section describes the effect of Fromm's
      Zen Buddhism and Psychoanalysis on the author of this paper, as he came to
      clinical psychology and psychoanalysis from involvement in Indian philosophy. The
      third section is a case study of a spiritually advanced Hindu woman seen in
      intensive short-term psychoanalytic therapy in Bombay, describing the interface
      of the spiritual with psychoanalytic therapy. The fourth section explains what
      eventually led to a sea change in psychoanalytic attitudes toward spiritual
      traditions and practices, with a small but significant group of psychoanalysts
      becoming involved in one or another spiritual practice, and working with patients
      also so involved.

PMID- 28746004
TI  - Is Fromm Relevant for Relational Approaches in Psychoanalysis?
AB  - This paper provides an overview of how Erich Fromm's work influenced contemporary
      relational and intersubjective approaches. It stresses Fromm's humanistic and
      existential sensibility, his explanation of how different socioeconomic and
      cultural contexts mold different character types, and how his center-to-center
      relatedness in clinical work all contribute to psychic change. The author shows
      how these dimensions intersect and add to current interests in relational
      psychoanalysis.

PMID- 28746005
TI  - When Worlds Collide: Sociology, Disciplinary Nightmares, and Fromm's Revision of
      Freud.
AB  - After decades of neglect, sociology is experiencing a revival of interest in
      psychoanalytic insights, and Erich Fromm's work is uniquely valuable for
      encouraging dialogue between the two fields. A recipient of a PhD in sociology as
      a young man in the 1920s, Fromm was a prominent psychoanalytic theorist and
      clinician, as well as a social researcher and public intellectual in the 1930s,
      up to his death in 1980. After a historical account of the relative neglect of
      Fromm in both disciplines, this paper examines the place of his psychoanalytic
      theory within sociology today as a way of discussing sociology's complicated
      relationship to psychoanalysis and the insights each field can offer the other.

PMID- 28746006
TI  - Erich Fromm and the Making and Unmaking of the Sociocultural.
AB  - This paper addresses issues of continuity and discontinuity regarding the role of
      the sociocultural in psychoanalysis. Starting with Freud's and Fromm's ideas on
      social change, the author discusses the dynamics whereby psychoanalytic culture
      gradually encouraged a process of delinking the psyche from the social. This
      disengagement from the sociocultural has encouraged dissociative mechanisms and
      social narcissism. Using a case study the author shows the importance of
      recapturing formulations that stress an analytic "Social Third."

PMID- 28746007
TI  - Learning and Doing: Working With Fromm and Applying What I Learned.
AB  - From 1960 to 1970 Erich Fromm was my teacher, analyst, and colleague. For the
      next ten years, we regularly corresponded about our work and views of public
      policy. As my analyst, Fromm had strengths and weaknesses. He influenced my
      research and practice on leadership and on transforming organizations to further
      both productivity and human development. His concepts can help us understand the
      current global political and cultural crisis that, while rooted in profound
      historic social, economic, and technological change, calls for depth
      psychological insights.

PMID- 28746008
TI  - Introduction to the Special Issue on Erich Fromm's Legacy.

PMID- 28746009
TI  - Choosing Life: Fromm's Clinical Values.
AB  - This paper explores some of the human values expressed in Erich Fromm's writing.
      Fromm passionately advocated for the importance of courage, integrity, self
      actualization, freedom, the cherishing of truth, and a fully alive presence in
      one's daily life. Some of the clinical implications of these values are
      discussed. The application of Fromm's beliefs to analytically oriented treatment
      is illustrated in a case vignette from the author's practice.

PMID- 28746010
TI  - Beyond Nature and Culture: Fromm's Existentialism.
AB  - Though commonly seen as a member of the so-called "culturistic" school of
      psychoanalysis that rejected Freudian drive theory and embraced an
      "oversocialized" conception of human nature, Fromm's qualified essentialism and
      neo-Marxist existentialism significantly transcend both biological and social
      determinism (although he succumbs to the latter in regard to his theory of the
      Oedipus complex). His existential Freudo-Marxism contributes to the integration
      of psychoanalysis and social science. In place of the authoritarian superego and
      the pseudo-objective stance of the classical Freudians, Fromm offers
      conscientious, egalitarian, personalistic, and humane values.

PMID- 28746011
TI  - Unexpected Gains: Being Overweight Buffers Asian Americans From Prejudice Against
      Foreigners.
AB  - Can being overweight, a factor that commonly leads to stigmatization, ironically
      buffer some people from race-based assumptions about who is American? In 10
      studies, participants were shown portraits that were edited to make the
      photographed person appear either overweight (body mass index, or BMI > 25) or
      normal weight (BMI < 25). A meta-analysis of these studies revealed that
      overweight Asian individuals were perceived as significantly more American than
      normal-weight versions of the same people, whereas this was not true for White,
      Black, or Latino individuals. A second meta-analysis showed that overweight Asian
      men were perceived as less likely to be in the United States without
      documentation than their normal-weight counterparts. A final study demonstrated
      that weight stereotypes about presumed countries of origin shape who is
      considered American. Taken together, these studies demonstrate that perceptions
      of nationality are malleable and that perceived race and body shape interact to
      inform these judgments.

PMID- 28746012
TI  - Screening Needed: Leprosy.

PMID- 28746013
TI  - Teaching About Human Papillomavirus: Lessons Learned.
AB  - Occupational and environmental health nurses play a critical role in educating
      the public about human papillomavirus (HPV). With HPV vaccination rates remaining
      low, creative educational models should be explored.

PMID- 28746014
TI  - Corrigendum.
AB  - Arbury, S., Zankowski, D., Lipscomb, J., & Hodgson, M. (2017). Workplace violence
      training programs for health care workers: an analysis of program elements.
      Workplace Health & Safety, 65(6), 266-272. (Original DOI:
      10.1177/2165079916671534) In this article, the author list was incorrectly
      ordered in the OnlineFirst and print versions. It should have appeared as
      follows: Sheila Arbury, MPH, RN, Donna Zankowski, MPH, RN, COHN, Jane Lipscomb,
      PhD, RN, FAAN, and Michael Hodgson, MPH, MD. This error has been corrected in the
      online article.

PMID- 28746016
TI  - Response.

PMID- 28746017
TI  - Tumor Evolution, Heterogeneity, and Therapy for Our Patients With Advanced
      Cancer: How Far Have We Come?
AB  - The clinical and molecular heterogeneity of various cancer types is well
      documented. In the era of precision oncology whereby molecular profiling of
      tumors is incorporated into clinical care, both intra- and intertumoral molecular
      and genetic heterogeneity have been described. Together, they impact patient
      treatment and outcomes. Host genetics and the tumor microenvironment impact on
      tumor evolution and heterogeneity through variations in immune cell infiltration,
      stromal variations, and selection pressures from hypoxia or nutrient stress,
      among others. Tumor progression and exposure to therapeutic agents lead to
      further molecular evolution and heterogeneity that is clinically relevant.
      Moreover, tumors that evolve after diagnosis and as a function of therapy
      generally become more aggressive and refractory to available therapeutics,
      including targeted agents and immunotherapy. The evolving clinical and molecular
      heterogeneity of patient tumors can be explored with various clinical and
      research-based specimens and testing such as pre- and post-treatment biopsies;
      serial liquid biopsies; single cell analysis; PDX and organoid models; anatomic,
      functional, and molecular imaging; and rapid postmortem studies. Other factors
      that influence tumor heterogeneity include immune checkpoints, cancer stem cells,
      therapy-acquired resistance mechanisms that may occur through secondary
      mutations, and adaptive responses. Modern technologic advances for tumor
      characterization provide opportunities to understand tumor evolution and its
      impact on clinical outcomes to improve therapeutic regimens. Characterization of
      novel targets and development of effective therapeutics are needed to target
      heterogeneity and the evolution of resistance mechanisms.

PMID- 28746018
TI  - Splenic Abscess in Immunocompetent Patients Managed Primarily without
      Splenectomy: A Series of 7 Cases.
AB  - INTRODUCTION: Splenic abscesses are rare in immunocompetent adults. Despite
      advances in diagnosis and treatment, these abscesses are still potentially life
      threatening. Various factors have been reported to predispose otherwise
      immunocompetent adults to splenic abscesses. Splenectomy was once considered the
      "gold standard" treatment. However, the trend is shifting to a conservative
      approach. CASE DESCRIPTION: We describe seven cases of splenic abscess in
      immunocompetent adults, the cause of which ranged from tuberculosis to salmonella
      and was as rare as Plasmodium vivax. All the patients presented with fever
      (median duration = one month; range = one week to six years) and abdominal pain,
      and most also had weight loss. All patients were in their third to fifth decades
      of life. The patients were successfully treated with appropriate antibiotic
      therapy, after which they were clinically normal. DISCUSSION: A microbiological
      diagnosis of splenic abscess is of utmost importance. In this series, all
      patients underwent percutaneous aspiration. This was performed under radiologic
      guidance (either ultrasonography or computed tomography). Only one patient
      required diagnostic splenectomy. Irrespective of whatever surgical or nonsurgical
      drainage measures are employed, appropriate antibiotic therapy is the cornerstone
      of management. The dose and duration of antibiotic therapy depend on the
      causative organism and its sensitivity pattern.

PMID- 28746019
TI  - Evaluation of a "Just-in-Time" Nurse Consultation on Bone Health: A Pilot
      Randomized Controlled Trial.
AB  - CONTEXT: Evidence is inconclusive whether a nurse consultation can improve
      osteoporosis-related patient outcomes. OBJECTIVE: To evaluate whether a nurse
      consultation immediately after dual-energy x-ray absorptiometry (DXA) produced
      better osteoporosis-related outcomes than a simple intervention to activate
      adults in good bone health practices or usual care. DESIGN: Pilot randomized
      controlled trial, conducted within the larger Patient Activation After DXA Result
      Notification (PAADRN) trial (NCT01507662). After DXA, consenting adults age 50
      years or older were randomly assigned to 3 groups: nurse consultation, PAADRN
      intervention (mailed letter with individualized fracture risk and an educational
      brochure), or usual care (control). Nurse consultation included reviewing DXA
      results, counseling on bone health, and ordering needed follow-up tests or
      physician referrals. MAIN OUTCOME MEASURES: Change from baseline to 52 weeks in
      participant-reported osteoporosis-related pharmacotherapy, lifestyle, activation
      and self-efficacy, and osteoporosis care satisfaction. RESULTS: Nurse
      consultation participants (n = 104) reported 52-week improvements in
      strengthening and weight-bearing exercise (p = 0.09), calcium intake (p < 0.01),
      osteoporosis knowledge (p = 0.04), activation (p < 0.01), dietary self-efficacy
      (p = 0.06), and osteoporosis care satisfaction (p < 0.01). Compared with PAADRN
      intervention participants (n = 39), nurse consultation participants had improved
      dietary self-efficacy (p = 0.07) and osteoporosis care satisfaction (p = 0.05).
      No significant improvements in osteoporosis-related outcomes were achieved vs
      PAADRN controls (n = 70). CONCLUSION: "Just-in-time" nurse consultation yielded a
      few improvements over 52 weeks in osteoporosis-related outcomes; however, most
      changes were not different from those obtained through the lower-cost PAADRN
      intervention or usual care.

PMID- 28746020
TI  - Pembrolizumab-Induced Pancytopenia: A Case Report.
AB  - INTRODUCTION: Programmed death receptor-1 blockade with pembrolizumab is approved
      by the US Food and Drug Administration to treat patients with metastatic
      melanoma. Activating T cells to fight cancer may cause immune-mediated adverse
      events. Pembrolizumab-induced pancytopenia has not been previously reported in
      the medical literature, to our knowledge. CASE PRESENTATION: A 52-year-old
      Caucasian woman with a diagnosis of metastatic melanoma of the rectum experienced
      multiple adverse events along her course of therapy with pembrolizumab, ranging
      from colitis, hepatitis, gastritis, and vitiligo after the fifth cycle of
      pembrolizumab; to knee synovitis after the 14th cycle; and to severe pancytopenia
      after the 18th cycle of pembrolizumab. Severe pancytopenia improved after high
      dose corticosteroids and a 5-day course of intravenous immunoglobulin therapy.
      DISCUSSION: In our case, pembrolizumab-induced Grade 4 pancytopenia resolved via
      a combination of corticosteroids and intravenous immunoglobulins. Pancytopenia
      reached a nadir in 10 weeks, and it took 16 weeks for meaningful recovery.

PMID- 28746021
TI  - Use of a Technetium99m-Sestamibi Scan to Detect Ipsilateral Double Adenoma in a
      Patient with Primary Hyperparathyroidism: A Case Report.
AB  - INTRODUCTION: Patients with primary hyperparathyroidism generally have a single
      parathyroid adenoma that causes excessive excretion of parathyroid hormone. For
      about 2% to 15% of these patients, a double adenoma is present that involves one
      lesion on each side of the neck. CASE PRESENTATION: We describe a case of double
      parathyroid adenoma causing asymptomatic hypercalcemia. A presurgical
      technetium99m (Tc99m) sestamibi scan suggested an ipsilateral double adenoma in
      the left thyroid lobe. An intraoperative parathyroid hormone assay confirmed its
      successful removal. DISCUSSION: Although double adenomas are not yet widely
      acknowledged, presurgical imaging and nuclear scans can help to localize multiple
      lesions, and intraoperative parathyroid hormone assays can confirm the diagnosis
      and cure.

PMID- 28746022
TI  - Mortality After Total Knee and Total Hip Arthroplasty in a Large Integrated
      Health Care System.
AB  - CONTEXT: The number of excess deaths associated with elective total joint
      arthroplasty in the US is not well understood. OBJECTIVE: To evaluate one-year
      postoperative mortality among patients with elective primary and revision
      arthroplasty procedures of the hip and knee. DESIGN: A retrospective analysis was
      conducted of hip and knee arthroplasties performed in 2010. Procedure type,
      procedure volume, patient age and sex, and mortality were obtained from an
      institutional total joint replacement registry. An integrated health care system
      population was the sampling frame for the study subjects and was the reference
      group for the study. MAIN OUTCOME MEASURES: Standardized 1-year mortality ratios
      (SMRs) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of
      10,163 primary total knee arthroplasties (TKAs), 4963 primary total hip
      arthroplasties (THAs), 606 revision TKAs, and 496 revision THAs were evaluated.
      Patients undergoing primary THA (SMR = 0.6, 95% CI = 0.4-0.7) and TKA (SMR = 0.4,
      95% CI = 0.3-0.5) had lower odds of mortality than expected. Patients with
      revision TKA had higher-than-expected mortality odds (SMR = 1.8, 95% CI = 1.1
      2.5), whereas patients with revision THA (SMR = 0.9, 95% CI = 0.4-1.5) did not
      have higher-than-expected odds of mortality. CONCLUSION: Understanding excess
      mortality after joint surgery allows clinicians to evaluate current practices and
      to determine whether certain groups are at higher-than-expected mortality risk
      after surgery.

PMID- 28746023
TI  - The Patient-Centered Medical Home as a Community-based Strategy.
AB  - Increasing attention has been devoted to the important role that primary care
      will play in improving population health. One innovation, the patient-centered
      medical home (PCMH), aims to unite a variety of professionals with patients in
      the prevention and treatment of illness. Although patient perspectives are
      critical to this model, this article questions whether the PCMH in practice is
      truly community-based. That is, do physicians, planners, and other health care
      professionals take seriously the value of integrating local knowledge into
      medical care? The argument presented is that community-based philosophy contains
      a foundational principle that the perspectives of health care practitioners and
      community members must be integrated. Although many proponents of the PCMH aim to
      offer patient-centered and sustainable health care, focusing on this
      philosophical shift will ensure that services are organized by communities in
      collaboration with health care professionals.

PMID- 28746024
TI  - Impact of Longitudinal Electronic Health Record Training for Residents Preparing
      for Practice in Patient-Centered Medical Homes.
AB  - INTRODUCTION: Competence in using an electronic health record (EHR) is considered
      a critical skill for physicians practicing in patient-centered medical homes
      (PCMHs), but few studies have examined the impact of EHR training for residents
      preparing to practice in PCMHs. This study explored the educational outcomes
      associated with comprehensive EHR training for family medicine residents.
      METHODS: The PCMH EHR training consisted of case-based routine clinic visits
      delivered to 3 resident cohorts (N = 18). Participants completed an EHR
      competency self-assessment between 2011 and 2016 (N = 127), examining 6 EHR/PCMH
      core skills. We compared baseline characteristics for residents by low vs high
      exposure to EHR training. Multivariate regression estimated whether self-reported
      competencies improved over time and whether high PCMH EHR training exposure was
      associated with incremental improvement in self-reported competencies over time.
      RESULTS: Residents completed an average of 8.2 sessions: low-exposure residents
      averaged 5.3 sessions (standard deviation = 1.5), and high-exposure residents
      averaged 9.0 sessions (standard deviation = 0.9). High-exposed residents had
      higher posttest scores at training completion (84.4 vs 70.7). Over time, adjusted
      mean scores (confidence interval) for both groups improved (p < 0.001) from 12.2
      (9.6-14.8), with low-exposed residents having greater score improvement (p <
      0.001) because of their much lower baseline scores. CONCLUSION: Comprehensive
      training designed to improve EHR competencies among residents practicing in a
      PCMH resulted in improved assessment scores. Our findings indicate EHR training
      as part of resident exposure to the PCMH measurably improves self-assessed
      competencies, even among residents less engaged in EHR training.

PMID- 28746025
TI  - "It Keeps Us from Putting Drugs in Pockets": How a Public-Private Partnership for
      Hospital Management May Help Curb Corruption.
AB  - INTRODUCTION: Health care sector corruption diverts resources that could
      otherwise be used to improve access to health services. Use of private-sector
      practices such as a public-private partnership (PPP) model for hospital
      governance and management may reduce corruption. In 2011, a government-run
      hospital in Lesotho was replaced by a PPP hospital, offering an opportunity to
      compare hospital systems and practices. OBJECTIVE: To assess whether a PPP model
      in a hospital can help curb corruption. METHODS: We conducted 36 semistructured
      interviews with key informants between February 2013 and April 2013. We asked
      about hospital operations and practices at the government-run and PPP hospitals.
      We performed content analysis of interview data using a priori codes derived from
      the Corruption in the Health Sector framework and compared themes related with
      corruption between the hospitals. RESULTS: Corrupt practices that were described
      at the government-run hospital (theft, absenteeism, and shirking) were absent in
      the PPP hospital. In the PPP hospital, anticorruption mechanisms (controls on
      discretion, transparency, accountability, and detection and enforcement) were
      described in four management subsystems: human resources, facility and equipment
      management, drug supply, and security. CONCLUSION: The PPP hospital appeared to
      reduce corruption by controlling discretion and increasing accountability,
      transparency, and detection and enforcement. Changes imposed new norms that
      supported personal responsibility and minimized opportunities, incentives, and
      pressures to engage in corrupt practices. By implementing private-sector
      management practices, a PPP model for hospital governance and management may curb
      corruption. To assess the feasibility of a PPP, administrators should account for
      cost savings resulting from reduced corruption.

PMID- 28746026
TI  - Complementary and Alternative Medicine in an Integrated Health Care Delivery
      System: Users of Chiropractic, Acupuncture, and Massage Services.
AB  - INTRODUCTION: Complementary and alternative medicine research has relied
      primarily on survey data from community populations rather than from patient
      populations receiving these services in integrated health care delivery systems
      (IHDS). OBJECTIVES: To describe patients seeking chiropractic, acupuncture, or
      massage therapy in a dedicated Center for Complementary Medicine (CCM) within an
      IHDS. METHODS: Patient surveys at the initial CCM visit included chief complaint,
      prior treatments, and relief with treatment (0% to 100% relief). A modified Brief
      Pain Inventory assessed average and current pain (0 = no pain; 10 = unbearable
      pain) and interference with life domains (1 = does not interfere; 10 = completely
      interferes). Demographics and CCM provider type were obtained from medical
      records. Analysis included patients who completed the survey. RESULTS: Between
      2007 and 2014, a total of 27,225 patients sought CCM services (median age = 50
      years). Most (62%) were female, and 73% were white. Modalities included
      chiropractic (66.9%), acupuncture (18.1%), and massage (15.0%). Spine/truncal
      pain was most commonly reported (70.5%). A majority of patients (59%) saw their
      physician for their condition, 59% had not used CCM services previously, and 60%
      received medications for their condition. Mean ratings included pain relief with
      prior treatment (30.07%, standard deviation [SD] = 27.01%), current pain (4.33,
      SD = 2.4), and functional impairment ranging from 3.03 (SD = 3.09) for
      relationships to 5.42 (SD = 3.22) for enjoyment of life. CONCLUSION:
      Spine/truncal pain was the most common complaint and chiropractic the most common
      modality among patients receiving CCM services in an IHDS. More than one-third of
      patients self-referred to the CCM.

PMID- 28746027
TI  - Abdominal Distension-An Unexpected Gift.

PMID- 28746028
TI  - The Kaiser Permanente Northern California Enhanced Recovery After Surgery
      Program: Design, Development, and Implementation.
AB  - Complications are common after surgery, highlighting the need for innovations
      that reduce postsurgical morbidity and mortality. In this report, we describe the
      design, development, and implementation of an Enhanced Recovery After Surgery
      program in the Kaiser Permanente Northern California integrated health care
      delivery system. This program was implemented and disseminated in 2014, targeting
      patients who underwent elective colorectal resection and those who underwent
      emergent hip fracture repair across 20 Medical Centers. The program leveraged
      multidisciplinary and broad-based leadership, high-quality data and analytic
      infrastructure, patient-centered education, and regional-local mentorship
      alignment. This program has already had an impact on more than 17,000 patients in
      Northern California. It is now in its fourth phase of planning and
      implementation, expanding Enhanced Recovery pathways to all surgical patients
      across Kaiser Permanente Northern California.

PMID- 28746030
TI  - Searching for epilepsy's crystal ball.
AB  - Multi-modal MRI techniques have identified biomarkers that could help to predict
      whether someone will develop epilepsy.

PMID- 28746029
TI  - Early tissue damage and microstructural reorganization predict disease severity
      in experimental epilepsy.
AB  - Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults
      and is often refractory to medication. So far, resection of the epileptogenic
      focus represents the only curative therapy. It is unknown whether pathological
      processes preceding epilepsy onset are indicators of later disease severity.
      Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue
      reorganization during epileptogenesis in a mouse mTLE model. The prognostic value
      of MRI biomarkers was assessed by retrospective correlations with pathological
      hallmarks Here, we show for the first time that the extent of early hippocampal
      neurodegeneration and progressive microstructural changes in the dentate gyrus
      translate to the severity of hippocampal sclerosis and seizure burden in chronic
      epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the
      extent of sclerosis in human hippocampi. Our findings may allow an early
      prognosis of disease severity in mTLE before its first clinical manifestations,
      thus expanding the therapeutic window.

PMID- 28746031
TI  - Incidence of Biliary Atresia and Timing of Hepatoportoenterostomy in the United
      States.
AB  - OBJECTIVE: To evaluate the incidence, trends, seasonality, and age at the time of
      hepatoportoenterostomy (Kasai procedure) for biliary atresia in the US. STUDY
      DESIGN: The triennial Health Cost and Utilization Project-Kids' Inpatient
      Database for 1997-2012 was used to perform a retrospective analysis of biliary
      atresia in the US. Infants aged <1 year of age with a diagnosis of biliary
      atresia who underwent a Kasai procedure were included. Nationwide infant
      population data were used to calculate incidence and evaluate trends. Age at the
      time of the Kasai procedure and the seasonality of biliary atresia were evaluated
      as well. RESULTS: The incidence of biliary atresia in the US was 4.47 per 100 000
      and was higher in females (risk ratio [RR], 1.43; 95% CI, 1.27-1.62),
      Asian/Pacific Islanders (RR, 1.89; 95% CI, 1.44-2.47), and blacks (RR, 1.30; 95%
      CI, 1.06-1.58) compared with whites. The incidence of biliary atresia increased
      by an average of 7.9% per year from 1997 to 2012 (P <.001). The median age at the
      time of the Kasai procedure was 63 days, with no improvement over the study
      period (P = .64). There was no evidence of seasonality (P = .69). CONCLUSION: The
      incidence of biliary atresia has increased over the past 15 years, with the
      median age at the time of the Kasai procedure now outside the optimal window.
      Implementation of systematic screening measures for biliary atresia in the US are
      needed.

PMID- 28746032
TI  - Early Mortality and Morbidity in Infants with Birth Weight of 500 Grams or Less
      in Japan.
AB  - OBJECTIVE: To assess the short-term prognosis of Japanese infants with a birth
      weight (BW) of <=500 g. STUDY DESIGN: Demographic and clinical data were reviewed
      for 1473 live born infants with a BW <=500 g at gestational age >=22 weeks who
      were treated in the 204 affiliated hospitals of the Neonatal Research Network of
      Japan between 2003 and 2012. RESULTS: Survival to hospital discharge occurred in
      811 of 1473 infants (55%; 95% CI 53%-58%). The survival rates of BW <=300 g, 301
      400 g, and 401-500 g were 18% (95% CI 10%-31%), 41% (95% CI 36%-47%), and 60%
      (95% CI 57%-63%), respectively. In a multivariable Cox proportional hazards
      analysis, antenatal corticosteroid use (adjusted hazard ratio: 0.68; 95% CI 0.58
      0.81; P < .01), cesarean delivery (0.69; 95% CI 0.56-0.85; P < .01), advanced
      gestational age per week (0.94; 95% CI 0.89-0.99; P = .02), BW per 100-g increase
      (0.55; 95% CI 0.49-0.64; P < .01), Apgar score >=4 at 5 minutes (0.51; 95% CI
      0.43-0.61; P < .01), and no major congenital abnormalities (0.38; 95% CI 0.29
      0.51; P < .01) were associated with survival to discharge. Despite the improved
      survival rate over the 10-year study period (from 40% in 2003 [95% CI 30%-51%] to
      68% in 2012 [95% CI 61%-75%]), at least 1 severe morbidity was present in 81%-89%
      of the survivors. CONCLUSIONS: Improvements in perinatal-neonatal medicine have
      improved the survival, but not the rate of major morbidities, of infants with a
      BW <=500 g in Japan.

PMID- 28746033
TI  - The importance of family presence, and how to make it happen.

PMID- 28746034
TI  - The next generation is here now.

PMID- 28746035
TI  - Diet, arsenic, and clinical research.

PMID- 28746036
TI  - Epinephrine in neonatal resuscitation: more information on what works and doesn't
      work.

PMID- 28746038
TI  - Corrections.

PMID- 28746037
TI  - Corticosteroids for children with parapneumonic effusion.

PMID- 28746040
TI  - Laparoscopic surgery in children with congenital heart disease.

PMID- 28746039
TI  - Corrections.

PMID- 28746041
TI  - Barriers to prevent disability due to leprosy in children are breachable.

PMID- 28746042
TI  - 50 Years Ago in The Journal of Pediatrics: Double-Blind Treatment Study of
      Shigellosis Comparing Ampicillin, Sulfadiazine, and Placebo.

PMID- 28746043
TI  - 50 Years Ago in The Journal of Pediatrics: Monarticular Juvenile Rheumatoid
      Arthritis.

PMID- 28746044
TI  - Various glycolysis inhibitor-containing tubes for glucose measurement cannot be
      used interchangeably due to clinically unacceptable biases between them.
AB  - BACKGROUND: The aim of our study was to determine the difference between glucose
      concentration measured 30 min after venipuncture in ice-chilled heparin plasma
      sample and all currently available citrate buffer-containing tubes (Greiner
      Glucomedics, Greiner FC Mix and Sarstedt GlucoEXACT) and still widely used sodium
      fluoride/potassium oxalate (NaF/Kox) tubes from Greiner. METHODS: Blood was
      collected from 20 healthy volunteers and 20 patients with diabetes into LiH,
      NaF/KOx, Glucomedics, FC mix and GlucoEXACT tubes. Glucose was measured within 30
      min from blood sampling in duplicate on the Architect c8000 analyzer. Mean biases
      between all tube types were calculated and compared to the recommended criteria
      (1.95%). Additionally, glucose concentrations measured in all five tube types
      were compared using the Friedman test. RESULTS: In the entire studied population,
      glucose concentrations measured in Glucomedics, FC mix and GlucoEXACT were higher
      (7.3%, 3.2% and 2.0%, respectively) than in the ice-chilled LiH tubes. When all
      glycolysis inhibitor-containing tubes were compared, Glucomedics tubes
      significantly differed from GlucoEXACT and FC mix tubes (biases -4.9% and 4.0%,
      respectively). In addition, there was a significant difference between the
      NaF/KOx tube and Glucomedics, as well as FC mix tubes (biases 7.1% and 3.0%,
      respectively). CONCLUSIONS: Glucose concentrations measured in recommended ice
      chilled lithium heparin- and citrate buffer-containing tubes are not comparable.
      Significant biases exist between various glycolysis inhibitor-containing tubes;
      therefore, they cannot be used interchangeably.

PMID- 28746045
TI  - Applicability of biotechnologically produced insect silks.
AB  - Silks are structural proteins produced by arthropods. Besides the well-known
      cocoon silk, which is produced by larvae of the silk moth Bombyx mori to undergo
      metamorphosis inside their silken shelter (and which is also used for textile
      production by men since millennia), numerous further less known silk-producing
      animals exist. The ability to produce silk evolved multiple independent times
      during evolution, and the fact that silk was subject to convergent evolution gave
      rise to an abundant natural diversity of silk proteins. Silks are used in air,
      under water, or like honey bee silk in the hydrophobic, waxen environment of the
      bee hive. The good mechanical properties of insect silk fibres together with
      their non-toxic, biocompatible, and biodegradable nature renders these materials
      appealing for both technical and biomedical applications. Although nature
      provides a great diversity of material properties, the variation in quality
      inherent in materials from natural sources together with low availability (except
      from silkworm silk) impeded the development of applications of silks. To overcome
      these two drawbacks, in recent years, recombinant silks gained more and more
      interest, as the biotechnological production of silk proteins allows for a
      scalable production at constant quality. This review summarises recent
      developments in recombinant silk production as well as technical procedures to
      process recombinant silk proteins into fibres, films, and hydrogels.

PMID- 28746051
TI  - Stanozolol-soaked grafts enhance new bone formation in rat calvarial critical
      size defects.
AB  - Androgen hormones play a significant role in regulating bone morphogenesis and in
      maintaining bone homeostasis throughout life. This study aimed to investigate the
      local effects of the non-aromatizable androgen stanozolol (ST) on bone
      regeneration in rats. Bilateral critical-size defects were created in the
      parietal bone of 26 male Wistar rats: the defect on one side was filled with a
      deproteinized bovine bone scaffold (DBB) soaked in ST solution (test) and the
      contralateral with DBB alone (control). Samples were collected at one month and
      three months. Histomorphometry revealed a significantly higher new bone formation
      (NB) (24.41% +/- 4.14% versus 15.01% +/- 2.43%, p < 0.05) and mineral apposition
      rate (MAR) (9.20 MUm/day +/- 0.37 versus 6.50 MUm/day +/- 1.09, p < 0.05) in the
      test versus control group at one month. Accordingly, real time-polymerase chain
      reaction revealed a consistently higher Runx2 expression in test samples (fold
      change test/control: 4.50 +/- 1.17, p <= 0.05). No morphometrical differences
      between groups were detected at three months (p > 0.05). However, test samples
      were characterized by an increase in blood capillary density from one month
      (11.43 n mm-2 +/- 2.01) to three months (28.26 n mm-2 +/- 5.62), providing
      evidence of a vital remodeling tissue. Control samples presented a decrease of
      anti-Osterix (SP7)/anti-osteocalcin (BGLAP) (3.9 n mm-2 +/- 0.32 versus 1.01 n mm
      2 +/- 0.20) and alkaline phosphatase (ALP) (12.14 n mm-2 +/- 6.29 versus 6.29 n
      mm-2 +/- 2.73) immunohistochemical-positive elements, which was suggestive of a
      stabilized healing phase. Based on these observations, local ST administration
      boosted bone regeneration in rat calvarial critical-size defects at one month.
      This study showed the potential of local steroid delivery in bone regeneration.

PMID- 28746052
TI  - Detection and characterization of intermittent complexity variations in cardiac
      arrhythmia.
AB  - OBJECTIVE: A frequent observation during cardiac fibrillation is a fluctuation in
      complexity where the irregular pattern of the fibrillation is interrupted by more
      regular phases of varying length. APPROACH: We apply different measures to
      sliding windows of raw ECG signals for quantifying the temporal complexity. The
      methods include permutation entropy, power spectral entropy, a measure for the
      extent of the set of reconstructed states and several wavelet measures. MAIN
      RESULTS: Using these methods, variations of fibrillation patterns over time are
      detected and visualized. SIGNIFICANCE: These quantifications can be used to
      characterize different phases of the ECG during fibrillation and might improve
      diagnosis and treatment methods for heart diseases.

PMID- 28746053
TI  - Bacterial attachment on titanium surfaces is dependent on topography and chemical
      changes induced by nonthermal atmospheric pressure plasma.
AB  - Here, we investigated the antibacterial effects of chemical changes induced by
      nonthermal atmospheric pressure plasma (NTAPP) on smooth and rough Ti. The
      morphologies of smooth and rough surfaces of Ti were examined using scanning
      electron microscopy (SEM). Both Ti specimens were then treated for 10 min by
      NTAPP with nitrogen gas. The surface roughness, chemistry, and wettability were
      examined by optical profilometry, x-ray photoelectron spectroscopy, and water
      contact angle analysis, respectively. Bacterial attachment was measured by
      determining the number of colony forming units and by SEM analysis. The rough Ti
      showed irregular micropits, whereas smooth Ti had a relatively regular pattern on
      the surface. There were no differences in morphology between samples before and
      after NTAPP treatment. NTAPP treatment resulted in changes from hydrophobic to
      hydrophilic properties on rough and smooth Ti; rough Ti showed relatively higher
      hydrophilicity. Before NTAPP treatment, Streptococcus sanguinis (S. sanguinis)
      showed greater attachment on rough Ti, and after NTAPP treatment, there was a
      significant reduction in bacterial attachment. Moreover, the bacterial attachment
      rate was significantly lower on rough Ti, and the structure of S. sanguinis
      colonies were significantly changed on NTAPP-treated Ti. NTAPP treatment
      inhibited bacterial attachment surrounding titanium implants, regardless of
      surface topography. Therefore, NTAPP treatment on Ti is a next-generation tool
      for antibacterial applications in the orthopaedic and dental fields.

PMID- 28746054
TI  - Nutritional Deficiency-Related Oral and Cutaneous Lesions in an Obese Patient.
AB  - The cutaneous and oral lesions related to nutritional deficiencies are scarcely
      reported. Micronutrient deficiencies may significantly affect mouth mucosa and
      skin, causing great morbidity. We report an extraordinary case with detailed
      clinical and microscopic findings affecting the oral cavity and skin. Physicians
      must be familiar with these manifestations to suspect the diagnosis.

PMID- 28746055
TI  - A Verrucous Plaque on the Abdomen: Challenge.

PMID- 28746056
TI  - Volar Papulonodules in a Patient With Seronegative Rheumatoid Arthritis:
      Challenge.

PMID- 28746057
TI  - Solid lipid nanoparticles improve octyl gallate antimetastatic activity and
      ameliorate its renal and hepatic toxic effects.
AB  - Metastasis is the main cause of cancer-related death and requires the development
      of effective treatments with reduced toxicity and effective anticancer activity.
      Gallic acid derivatives have shown significant biological properties including
      antitumoral activity as shown in a previous study with octyl gallate (G8) in
      vitro. Thus, the aim of this work was to evaluate the antimetastatic effect of
      free and solid lipid nanoparticle-loaded G8 in mice in a lung metastasis model.
      Animals inoculated with melanoma cells presented metastasis in lungs, which was
      significantly inhibited by treatment with G8 and solid lipid nanoparticle-loaded
      G8, named G8-NVM. However, G8-treated mice showed an increase in several
      toxicological parameters, which were almost completely circumvented by G8-NVM
      treatment. This study supports the need for pharmacological studies on new
      potential medicinal plants to treat cancer and can provide new perspectives on
      using nanotechnology to improve biological activities while decreasing the
      chemotherapy toxicological effects of anticancer drugs.

PMID- 28746058
TI  - Rapid Number Naming and Quantitative Eye Movements May Reflect Contact Sport
      Exposure in a Collegiate Ice Hockey Cohort.
AB  - BACKGROUND: The King-Devick (K-D) test of rapid number naming is a reliable
      visual performance measure that is a sensitive sideline indicator of concussion
      when time scores worsen (lengthen) from preseason baseline. Within cohorts of
      youth athletes <18 years old, baseline K-D times become faster with increasing
      age. We determined the relation of rapid number-naming time scores on the K-D
      test to electronic measurements of saccade performance during preseason baseline
      assessments in a collegiate ice hockey team cohort. Within this group of young
      adult athletes, we also sought to examine the potential role for player age in
      determining baseline scores. METHODS: Athletes from a collegiate ice hockey team
      received preseason baseline testing as part of an ongoing study of rapid rink
      side performance measures for concussion. These included the K-D test (spiral
      bound cards and tablet computer versions). Participants also performed a
      laboratory-based version of the K-D test with simultaneous infrared-based video
      oculographic recordings using an EyeLink 1000+. This allowed measurement of the
      temporal and spatial characteristics of eye movements, including saccadic
      velocity, duration, and intersaccadic interval (ISI). RESULTS: Among 13 male
      athletes, aged 18-23 years (mean 20.5 +/- 1.6 years), prolongation of the ISI (a
      combined measure of saccade latency and fixation duration) was the measure most
      associated with slower baseline time scores for the EyeLink-paired K-D (mean 38.2
      +/- 6.2 seconds, r = 0.88 [95% CI 0.63-0.96], P = 0.0001), the K-D spiral-bound
      cards (36.6 +/- 5.9 seconds, r = 0.60 [95% CI 0.08-0.87], P = 0.03), and K-D
      computerized tablet version (39.1 +/- 5.4 seconds, r = 0.79 [95% CI 0.42-0.93], P
      = 0.001). In this cohort, older age was a predictor of longer (worse) K-D
      baseline time performance (age vs EyeLink-paired K-D: r = 0.70 [95% CI 0.24
      0.90], P = 0.008; age vs K-D spiral-bound cards: r = 0.57 [95% CI 0.03-0.85], P =
      0.04; age vs K-D tablet version: r = 0.59 [95% CI 0.06-0.86], P = 0.03) as well
      as prolonged ISI (r = 0.62 [95% CI 0.11-0.87], P = 0.02). Slower baseline K-D
      times were not associated with greater numbers of reported prior concussions.
      CONCLUSIONS: Rapid number-naming performance using the K-D at preseason baseline
      in this small cohort of collegiate ice hockey players is best correlated with ISI
      among eye movement-recording measures. Baseline K-D scores notably worsened with
      increasing age, but not with numbers of prior concussions in this small cohort.
      While these findings require further investigation by larger studies of contact
      and noncontact sports athletes, they suggest that duration of contact sports
      exposure may influence preseason test performance.

PMID- 28746059
TI  - Nutrition (Micronutrients) in Child Growth and Development: A Systematic Review
      on Current Evidence, Recommendations and Opportunities for Further Research.
AB  - OBJECTIVE: An important aspect of malnutrition is deficiency of different
      micronutrients during pregnancy or early childhood. We systematically reviewed
      the role of nutrition in child growth (weight or height gain) and development.
      METHODS: A comprehensive literature search was done on PubMed/Cochrane Library
      browsing through 38,795 abstracts until December 31, 2016 to select systematic
      reviews/meta-analyses and individual randomized controlled trials (RCTs) of
      micronutrient supplementation. RESULTS: Micronutrients studied included iron,
      iodine, folate, zinc, calcium, magnesium, selenium, vitamin D, vitamin A, vitamin
      B complex, and multiple micronutrients. We summarize evidence with details and
      results of RCTs, highlight strengths/weaknesses, and critically interpret
      findings. Effects of breastfeeding-promotion, food-supplementation (complementary
      and school feeding), conditional-cash-transfers, and integrated
      nutrition/psychosocial interventions are discussed. CONCLUSION: Based on this
      evidence we make policy and programmatic recommendations for supplementation to
      mothers and children at high-risk of deficiency.

PMID- 28746060
TI  - The Clinical Functional Impairment Scale Development.
AB  - OBJECTIVE: The purpose of the project was to review content validity and assess
      the span of responses for the newly developed Clinical Functional Impairment
      Scale (CFIS). METHODS: A cross-sectional, content validity process using focus
      groups of developmental, behavioral pediatric clinicians was conducted. After
      qualitative analysis of the focus group data, adjustments were made in the CFIS
      based on the recommendations of the content experts. A survey was conducted of
      clinicians participating in the online Society of Developmental and Behavioral
      Pediatrics Discussion Board. Clinicians reviewed 2 case studies and used the CFIS
      to score severity and interval change of predetermined functional impairments.
      The amount of spread in the answers was assessed by calculating the index of
      dispersion. RESULTS: Qualitative analysis of the focus groups resulted in
      adjustment to the CFIS to 20 functional impairments, with a 5-point Likert scale
      of severity and a 7-point Likert scale of interval change. Ninety-four clinicians
      participated in the survey. The index of dispersion ranged from 0.49 to 0.88. The
      interval ratings of severity and interval change had lower dispersion ranges.
      CONCLUSION: The CFIS uses a mutual prioritization by the family and clinician of
      the child's functional impairments. The study demonstrated that the clinicians'
      ratings of the case studies were more variable in the initial symptom severity
      score than their ratings of symptom severity and interval change in symptoms.
      Further testing of the CFIS is planned using face-to-face clinical encounters and
      including parent/caregiver ratings of severity and interval change.

PMID- 28746061
TI  - Lengthening With Monolateral External Fixation Versus Magnetically Motorized
      Intramedullary Nail in Congenital Femoral Deficiency.
AB  - BACKGROUND: Limb lengthening for congenital femoral deficiency (CFD) with or
      without fibular hemimelia can be performed with both external and internal
      devices. The purpose of this study is to compare clinical outcomes of femoral
      lengthening utilizing monolateral external fixation versus a magnetically
      motorized intramedullary nail in patients with CFD with or without fibular
      hemimelia. METHODS: This retrospective review included 62 patients with femoral
      lengthening, 32 patients had monolateral external fixation (group A), 30 patients
      had internal lengthening nail (group B). Mean age in years was 9.4+/-3.8 and
      15.4+/-4.9 for groups A and B, respectively. Mean follow-up in years was 4.47+/
      2.7 and 1.86+/-0.7 years for groups A and B, respectively. RESULTS: Mean
      lengthening achieved was 5.6+/-1.7 and 4.8+/-1.4 cm for group A and group B,
      respectively (P=0.052). Mean distraction index was 0.7+/-0.2 mm/d for group A and
      0.7+/-0.2 mm/d for the group B (P=0.99). Mean consolidation index for group A was
      29.3+/-12.7 and 34.8+/-11.2 d/cm for group B (P=0.08). Mean arc of motion before
      surgery and at final follow-up were similar between groups (P=0.35). Group A had
      significantly less range of motion at the end of distraction (P=0.0007) and at
      consolidation (P<0.0001). Both groups had similar rates of obstacles and
      complications. A significant difference between groups was found in the total
      problems (P<0.001) specifically with pin site/superficial infection (P<0.0001).
      CONCLUSIONS: The intramedullary nail had superior range of motion during the
      lengthening phase and at consolidation and an overall lower problem complication
      rate, while maintaining similar distraction and healing indices to monolateral
      external fixation. Internal lengthening nails represent a significant advance in
      technology for CFD lengthening. LEVEL OF EVIDENCE: Level IV-therapeutic.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- 28746062
TI  - Hyperechoic renal medullary pyramids in a boy with Simpson-Golabi-Behmel
      syndrome.

PMID- 28746063
TI  - Left Atrial Appendage Resection During Minimally Invasive Aortic Valve Surgery
      via Right Minithoracotomy.
AB  - Here, we report concomitant resection of the left atrial appendage through the
      transverse sinus during minimally invasive aortic valve replacement via right
      anterolateral thoracotomy. The left atrial appendage was exposed by raising the
      collapsed ascending aorta and was safely resected using a surgical stapling
      device. This procedure is a feasible option in elderly patients, for whom a
      percutaneous procedure would be inappropriate, and could be useful for preventing
      thromboembolic and hemorrhagic complications.

PMID- 28746064
TI  - Precannulated Fenestrated Endovascular Aneurysm Repair Using Guidewire Fixator: A
      Novel Method Using the Liungman Guidewire Fixator.
AB  - OBJECTIVE: By using a guidewire fixator, the distal guidewire position can be
      secured in an artery. This new principle enables a method for fenestrated
      endovascular aortic repair where the connection between the aortic branches and
      the stent graft fenestrations is made before inserting and deploying the stent
      graft. METHODS: This is conducted using a fenestrated stent graft with preloaded
      catheters, through which the prepositioned and distally secured guidewires from
      the branches are inserted. RESULTS: This report covers the method when
      implementing a single fenestration stent graft in pig. CONCLUSIONS: Successful
      tests with single and dual fenestrated grafts have been conducted in pigs.

PMID- 28746065
TI  - Percutaneous Electrical Neurostimulation of Dermatome T6 for Short-term Weight
      Loss in Overweight and Obese Patients: Effect on Ghrelin Levels, Glucose, Lipid,
      and Hormonal Profile.
AB  - BACKGROUND: Percutaneous electrical neurostimulation of dermatome T6 (PENS T6),
      associated with a low-caloric diet, has previously demonstrated to achieve a
      reduction in the appetite perception, inducing a better compliance of the
      prescribed diet and finally leading to a greater weight loss. Ghrelin has been
      hypothesized to be implicated in the effect of PENS T6. The aim of this study was
      to evaluate the effect of PENS T6 with hypocaloric diet on appetite, weight loss
      and dietary compliance, and its association with plasma ghrelin levels, in
      comparison with PENS T6 associated with normocaloric diet, transcutaneous
      electrical neurostimulation of T11-T12 (placebo) with hypocaloric diet, and only
      hypocaloric diet. PATIENTS AND METHODS: A prospective, randomized study was
      performed. Patients with body mass index >25 kg/m were included. The subjects
      were randomized into 4 groups: patients undergoing PENS T6 in conjunction with a
      1200 kcal/d diet (group 1). Patients undergoing PENS T6 and following a
      normocaloric diet (group 2), patients undergoing transcutaneous electrical
      neurostimulation of dermatomes in right iliac fossa (T11-T12) and following a
      1200 kcal/d diet(group 3) and those patients following only a 1200 kcal/d diet
      (group 4). RESULTS: A total of 200 patients were included, 50 in each group. A
      significantly greater weight loss was obtained in patients following PENS T6
      combined with diet, when compared with the other groups. Patients undergoing PENS
      T6, associated or not to hypocaloric diet, experienced appetite reduction and
      lower ghrelin levels, when compared with the other groups. CONCLUSIONS: The
      greater weight loss experienced in the patients undergoing PENS T6 is associated
      with appetite reduction and greater diet compliance. Appetite reduction is
      associated with ghrelin decrease.

PMID- 28746066
TI  - Automatic honesty forgoing reward acquisition and punishment avoidance: a
      functional MRI investigation.
AB  - Recent neuroimaging investigations into human honesty suggest that honest moral
      decisions in individuals who consistently behave honestly occur automatically,
      without the need for active self-control. However, it remains unclear whether
      this observation can be applied to two different types of honesty: honesty
      forgoing dishonest reward acquisition and honesty forgoing dishonest punishment
      avoidance. To address this issue, a functional MRI study, using an incentivized
      prediction task in which participants were confronted with real and repeated
      opportunities for dishonest gain leading to reward acquisition and punishment
      avoidance, was conducted. Behavioral data revealed that the frequency of
      dishonesty was equivalent between the opportunities for dishonest reward
      acquisition and for punishment avoidance. Reaction time data demonstrated that
      two types of honest decisions in the opportunity for dishonest reward acquisition
      and punishment avoidance required no additional cognitive control. Neuroimaging
      data revealed that honest decisions in the opportunity for dishonest reward
      acquisition and those for punishment avoidance required no additional control
      related activity compared with a control condition in which no opportunity for
      dishonest behavior was given. These results suggest that honesty flows
      automatically, irrespective of the concomitant motivation for dishonesty leading
      to reward acquisition and punishment avoidance.

PMID- 28746067
TI  - Perturbing NR2B-PSD-95 interaction relieves neuropathic pain by inactivating
      CaMKII-CREB signaling.
AB  - Neuropathic pain is characterized by central sensitization. The interaction
      between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein
      95 (PSD-95) plays a major role in central sensitization. Here, we aimed to
      investigate the analgesic effect of disruption of the interaction between NMDAR
      and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic
      sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The
      expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein
      kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured
      using western blotting. A mimetic peptide Myr-NR2B9c was injected intrathecally
      to disrupt the interaction between PSD-95 and NR2B and detected by
      coimmunoprecipitation. Chronic dorsal root ganglia compression surgery induced
      thermal hyperalgesia and mechanical allodynia, and upregulated pain-related
      proteins such as phospho-NR2B, PSD-95, CaMKII, and CREB expressions in the spinal
      cord. Myr-NR2B9c disrupted the interaction between NR2B-containing NMDARs and PSD
      95 in the spinal cord. Intrathecal administration of Myr-NR2B9c attenuated
      neuropathic pain behaviors and downregulated the expressions of phospho-NR2B, PSD
      95, CaMKII, and CREB in the spinal cord. The present study indicates that
      dissociation of NR2B-containing NMDARs from PSD-95 inactivates CaMKII and CREB
      signaling and relieves pain.

PMID- 28746069
TI  - Barriers to Medical Students' Electronic Health Record Access Can Impede Their
      Preparedness for Practice.
AB  - Medical students need hands-on experience documenting clinical encounters as well
      as entering orders to prepare for residency and become competent physicians. In
      the era of paper medical records, students consistently acquired experience
      writing notes and entering orders as part of their clinical experience. Over the
      past decade, however, patient records have transitioned from paper to electronic
      form. This change has had the unintended consequence of limiting medical
      students' access to patient records. This restriction has meant that many
      students leave medical school without the appropriate medical record skills for
      transitioning to residency.In this article, the authors explore medical students'
      current access to electronic health records (EHRs) as well as policy proposals
      from medical societies, innovative models implemented at some U.S. medical
      schools, and other possible solutions to ensure that students have sufficient
      experiential learning opportunities with EHRs in clinical settings. They also
      contend that competence in the use of EHRs is necessary for students to become
      physicians who can harness the full potential of these tools rather than
      physicians for whom EHRs hinder excellent patient care. Finally, the authors
      argue that meaningful experiences using EHRs should be consistently incorporated
      into medical school curricula and that EHR-related skills should be rigorously
      assessed with other clinical skills.

PMID- 28746070
TI  - What the "Nonteaching" Service Can Teach Us.
AB  - "Teaching" services usually incorporate a cadre of learners such as resident
      physicians and medical students as part of the care team, led by a faculty
      physician. "Nonteaching" services, in contrast, are usually defined by the
      absence of resident physicians on the care team. The care for patients on a
      nonteaching service is frequently managed directly by a faculty or nonfaculty
      physician. Nonteaching services have grown in number and size at academic medical
      centers (AMCs) in response to regulatory requirements, operational demands, and
      efforts to improve clinical education. The allocation of patients to teaching and
      nonteaching services is frequently based on perceived teaching value of
      hospitalized patients, which can potentially lead to a number of unintended
      consequences for medical education, professional satisfaction, and patient care.
      Through a series of four lessons, the authors describe how the structure of
      nonteaching services can result in curricular gaps, devalue attending physicians,
      and undermine the educational and clinical missions of AMCs. Anticipating the
      continued expansion and evolution of nonteaching services, the authors propose
      seven design principles for nonteaching services to ensure robust education for
      students and resident physicians, advance quality of care, and enhance attending
      physician and patient experience.

PMID- 28746071
TI  - Toward a Utopian Model for Teaching and Nonteaching Services: Every Journey
      Begins With a First Step.
AB  - Nonteaching services are an imperfect step toward enabling inpatient teaching
      services to transition from an unregulated, natural state, driven solely by the
      exigencies of patient volume and throughput, to one that is more controlled and
      intends to achieve the proper balance between service and education. As career
      educators the authors prefer to view nonteaching services as critical components
      of an integrated system that enables the best possible patient care and learning,
      yet they acknowledge that, to meet the needs of patients and learners, teaching
      and nonteaching services alike must be truly complementary, collaborative, and
      integrated components of a single system.In this Invited Commentary the authors
      offer a "utopian" view of a teaching service in an institution that explicitly
      acknowledges its contract with society to transform health care delivery. In this
      setting, highly engaged teachers and learners are supported by a high-performing
      cast of an advanced practice provider, primary nurses, a social worker, a case
      manager, a clinical pharmacist, and an analyst. This group forms a Clinical
      Learning Unit (CLU) where the curriculum has evolved into an interdependent
      framework of basic, clinical, and systems science. CLUs train tomorrow's health
      care workforce through adaptive service learning made possible because the team
      has a manageable census, time for daily reflection, and inspiring relationships
      with trained teachers. CLUs cannot exist without complementary nonteaching
      services.Elsewhere in this issue Repp and colleagues outline seven design
      principles to improve nonteaching services. These are a good first step toward
      the utopian vision outlined by the authors.

PMID- 28746072
TI  - Accreditation of Medical Education Programs: Moving From Student Outcomes to
      Continuous Quality Improvement Measures.
AB  - Accreditation of undergraduate medical education programs aims to ensure the
      quality of medical education and promote quality improvement, with the ultimate
      goal of providing optimal patient care. Direct linkages between accreditation and
      education quality are, however, difficult to establish. The literature examining
      the impact of accreditation predominantly focuses on student outcomes, such as
      performances on national examinations. However, student outcomes present
      challenges with regard to data availability, comparability, and contamination.The
      true impact of accreditation may well rest in its ability to promote continuous
      quality improvement (CQI) within medical education programs. The conceptual model
      grounding this paper suggests accreditation leads medical schools to commit
      resources to and engage in self-assessment activities that represent best
      practices of CQI, leading to the development within schools of a culture of CQI.
      In line with this model, measures of the impact of accreditation on medical
      schools need to include CQI-related markers. The CQI orientation of organizations
      can be measured using validated instruments from the business and management
      fields. Repeated determinations of medical schools' CQI orientation at various
      points throughout their accreditation cycles could provide additional evidence of
      the impact of accreditation on medical education. Strong CQI orientation should
      lead to high-quality medical education and would serve as a proxy marker for the
      quality of graduates and possibly for the quality of care they provide.It is time
      to move away from a focus on student outcomes as measures of the impact of
      accreditation and embrace additional markers, such as indicators of
      organizational CQI orientation.

PMID- 28746073
TI  - Medicine as a Community of Practice: Implications for Medical Education.
AB  - The presence of a variety of independent learning theories makes it difficult for
      medical educators to construct a comprehensive theoretical framework for medical
      education, resulting in numerous and often unrelated curricular, instructional,
      and assessment practices. Linked with an understanding of identity formation, the
      concept of communities of practice could provide such a framework, emphasizing
      the social nature of learning. Individuals wish to join the community, moving
      from legitimate peripheral to full participation, acquiring the identity of
      community members and accepting the community's norms.Having communities of
      practice as the theoretical basis of medical education does not diminish the
      value of other learning theories. Communities of practice can serve as the
      foundational theory, and other theories can provide a theoretical basis for the
      multiple educational activities that take place within the community, thus
      helping create an integrated theoretical approach.Communities of practice can
      guide the development of interventions to make medical education more effective
      and can help both learners and educators better cope with medical education's
      complexity. An initial step is to acknowledge the potential of communities of
      practice as the foundational theory. Educational initiatives that could result
      from this approach include adding communities of practice to the cognitive base;
      actively engaging students in joining the community; creating a welcoming
      community; expanding the emphasis on explicitly addressing role modeling,
      mentoring, experiential learning, and reflection; providing faculty development
      to support the program; and recognizing the necessity to chart progress toward
      membership in the community.

PMID- 28746074
TI  - Understanding the Multidimensional Effects of Resident Duty Hours Restrictions: A
      Thematic Analysis of Published Viewpoints in Surgery.
AB  - PURPOSE: Individuals representing various surgical disciplines have expressed
      concerns with the impact of resident duty hours (RDH) restrictions on resident
      education and patient outcomes. This thematic review of published viewpoints
      aimed to describe the effects of these restrictions in surgery. METHOD: The
      authors conducted a qualitative systematic review of non-research-based
      literature published between 2003 and 2015. Articles were included if they
      focused on the RDH restrictions in surgery and resident wellness, health
      promotion, resident safety, resident education and/or training, patient safety,
      medical errors, and/or heterogeneity regarding training or disciplines. A
      thematic analysis approach guided data extraction. Contextual data were
      abstracted from the included articles to aid in framing the identified themes.
      RESULTS: Of 1,482 identified articles, 214 were included in the review. Most were
      from authors in the United States (144; 67%) and focused on the 80-hour workweek
      (164; 77%). The emerging themes were organized into three overarching categories:
      (1) impact of the RDH restrictions, (2) surgery has its own unique culture, and
      (3) strategies going forward. Published opinions suggested that RDH restrictions
      alone are insufficient to achieve the desired outcomes and that careful
      consideration of the surgical training model is needed to maintain the integrity
      of educational outcomes. CONCLUSIONS: Opinions from the surgical community
      highlight the complexity of issues surrounding the RDH restrictions and suggest
      that recent changes are not achieving all the desired outcomes and have resulted
      in unintended outcomes. From the perceptions of the various stakeholders in
      surgical education studied, areas for new policies were identified.

PMID- 28746075
TI  - Fatigue in Residency Education: Understanding the Influence of Work Hours
      Regulations in Europe.
AB  - PURPOSE: Although one proposed solution to the problem of fatigued medical
      trainees is the implementation of work hours regulations, concerns about the
      effectiveness of these regulations are growing. Canada remains one of the few
      Western jurisdictions without legislated regulation. Recent research suggests
      that fatigue is a complex social construct, rather than simply a lack of sleep;
      thus, the authors explored how regulations and fatigue are understood in
      countries with established work hours frameworks to better inform other
      jurisdictions looking to address trainee fatigue. METHOD: Using constructivist
      grounded theory methodology, the authors conducted individual, semistructured
      interviews in 2015-2016 with 13 postgraduate medical trainees from four European
      countries with established work hours regulations. Data collection and analysis
      proceeded iteratively, and the authors used a constant comparative approach to
      analysis. RESULTS: Trainees reported that they were commonly fatigued and that
      they violated the work hours restrictions for various reasons, including
      educational pursuits. Although they understood the regulations were legislated
      specifically to ensure safe patient care and optimize trainee well-being, they
      also described implicit meanings (e.g., monitoring for trainee efficiency) and
      unintended consequences (e.g., losing a sense of vocation). CONCLUSIONS: Work
      hours regulations carry multiple, conflicting meanings for trainees that are
      captured by three predominant rhetorics: the rhetoric of patient safety, of well
      being, and of efficiency. Tensions within each of those rhetorics reveal that
      managing fatigue within clinical training environments is complex. These findings
      suggest that straightforward solutions are unlikely to solve the problem of
      fatigue, assure patient safety, and improve trainee well-being.

PMID- 28746076
TI  - Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a
      randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian
      adaptive design (the SPRINT trial).
AB  - Neublastin (BG00010) is a first-in-class, glial cell-derived neurotrophic factor
      shown in preclinical studies and an early clinical trial to have potential for
      the treatment of neuropathic pain. SPRINT was a phase 2, multicenter, double
      blinded, placebo-controlled study to evaluate efficacy/safety of 5 neublastin
      doses (50, 150, 400, 800, and 1200 MUg/kg) administered as an intravenous
      injection 3 times/week for 1 week in patients with chronic painful lumbosacral
      radiculopathy, utilizing Bayesian response-adaptive study design. Primary
      endpoint was change from baseline in mean 24-hour average general pain intensity
      over a 5-day period (week 1) after the last dose, analyzed using a Bayesian
      normal dynamic linear model. One hundred seventy-six patients were randomized and
      received treatment (placebo n = 48, 50 MUg/kg n = 38, 150 MUg/kg n = 13, 400
      MUg/kg n = 16, 800 MUg/kg n = 20, 1200 MUg/kg n = 41). Among the tested
      neublastin doses, the lowest dose (50 MUg/kg) showed the greatest difference from
      placebo for change from baseline in mean average general pain intensity at week 1
      after last dose, followed by the highest dose (1200 MUg/kg) (posterior mean
      difference -1.36 [95% credible interval -2.22 to -0.52] and -0.75 [-1.59 to
      0.08], respectively). Similar trends were observed in secondary efficacy
      endpoints. The most common adverse event in all neublastin dose groups was
      pruritus (79% vs 10% with placebo). There was no dose-response relationship with
      respect to primary/secondary efficacy outcomes or incidence of pruritus, despite
      dose-proportional increases in serum neublastin concentrations. In conclusion,
      while this study showed some evidence of pain relief with neublastin,
      particularly at the lowest dose, there was no clear dose-response relationship
      for pain reduction or the most common adverse event of pruritus.

PMID- 28746077
TI  - Disrupted offset analgesia distinguishes patients with chronic pain from healthy
      controls.
AB  - Offset analgesia (OA) represents a disproportionately large decrease of pain
      perception after a brief, temporary increment of thermal pain stimulus and was
      reported attenuated in patients with neuropathic pain. We examined whether OA
      depends on the increment duration before offset, and whether individual features
      of OA distinguish patients with chronic pain and healthy controls. We used a
      Peltier-type thermal stimulator and OA paradigms including 5-, 10-, or 15-s
      duration of 1 degrees C-increment (T2) over 45 degrees C. We first examined OA
      response, on the left volar forearm, at 3 different T2's in 40 healthy
      volunteers, and OA and constant stimulus responses in 12 patients with chronic
      pain and 12 matched healthy controls. We measured magnitude of OA ([INCREMENT]OA)
      and maximum visual analogue scale (VAS) latency (time to peak VAS) during
      constant stimulus for each individual. Pain perception kinetics were compared
      with analysis of variance and sought for correlations with psychophysical
      parameters with a significance threshold at P < 0.05. In healthy controls, longer
      T2 at 10 or 15 seconds resulted in larger [INCREMENT]OA compared with T2 at 5
      seconds (P = 0.04). In patients, [INCREMENT]OA was significantly smaller than
      controls at T2 = 5 or 10 seconds (P < 0.05) but grew comparable at T2 = 15
      seconds with controls. Maximum VAS latency was longer in patients than in
      controls and negatively correlated with [INCREMENT]OA in patients. An OA index
      ([INCREMENT]OA/[maximum VAS latency]) proved diagnostic of chronic pain with an
      area under the receiver operating characteristic curve at 0.897. Patients with
      chronic pain showed impairment of OA and reduced temporal sharpening of pain
      perception, which might imply possible disturbance of the endogenous pain
      modulatory system.

PMID- 28746078
TI  - Spinal microglia are required for long-term maintenance of neuropathic pain.
AB  - While spinal microglia play a role in early stages of neuropathic pain etiology,
      whether they are useful targets to reverse chronic pain at late stages remains
      unknown. Here, we show that microglia activation in the spinal cord persists for
      >3 months following nerve injury in rodents, beyond involvement of
      proinflammatory cytokine and chemokine signalling. In this chronic phase,
      selective depletion of spinal microglia in male rats with the targeted
      immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor-TrkB
      signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost
      completely reversed pain hypersensitivity. By contrast, local spinal
      administration of Mac1-saporin did not affect nociceptive withdrawal threshold in
      control animals nor did it affect the strength of afferent-evoked synaptic
      activity in the spinal dorsal horn in normal conditions. These findings show that
      the long-term, chronic phase of nerve injury-induced pain hypersensitivity is
      maintained by microglia-neuron interactions. The findings also effectively
      separate the central signalling pathways underlying the maintenance phase of the
      pathology from the early and peripheral inflammatory reactions to injury,
      pointing to different targets for the treatment of acute vs chronic injury
      induced pain.

PMID- 28746079
TI  - Distribution of Esophageal Motor Disorders in Diabetic Patients With Dysphagia.
AB  - BACKGROUND: Diabetes mellitus can cause various gastrointestinal symptoms.
      Assessment of esophageal dysmotility in diabetic patients has been scarcely
      studied. The aim of this study was to determine the esophageal motor
      characteristics of diabetic versus nondiabetic patients who present with
      dysphagia. METHODS: High-resolution esophageal manometries (HREMs) of 83 diabetic
      patients and 83 age and gender-matched nondiabetic patients with dysphagia from 2
      medical centers were included in this study. Demographic information, medical
      comorbidities, and medication usage were recorded for each patient in a single
      registry. HREM of each patient was evaluated and the different functional
      parameters were recorded. KEY RESULTS: Overall, 46% of diabetic patients were
      found to have an esophageal motor disorder. Diabetic patients with dysphagia were
      more likely to have failed swallows on HREM (50.6% vs. 33.7%; P=0.03) as compared
      with nondiabetic patients. Among diabetic patients, those being treated with
      insulin were more likely to have failed (69.0% vs. 40.7%; P=0.01) and weak (65.5%
      vs. 33.3%; P=0.005) swallows as compared with diabetic patients not on insulin.
      Among diabetic patients, those with abnormal manometry were more likely to
      demonstrate diabetic retinopathy (27.0% vs. 8.7%; P=0.04). There was a trend
      toward increased incidence of esophagogastric junction outflow obstruction in
      diabetic patients (10.8% vs. 2.4%; P=0.057) as compared with nondiabetic
      patients. CONCLUSIONS: Nearly half of diabetic patients with dysphagia have some
      type of an esophageal motility disorder. Diabetic retinopathy and the use of
      insulin are predictive of esophageal motor abnormalities among diabetic patients.

PMID- 28746080
TI  - Determination of Optimal Coronary Flow for the Preservation of "Donation after
      Circulatory Death" in Murine Heart Model.
AB  - Donation after circulatory death donors (DCD) have the potential to increase the
      number of heart transplants. The DCD hearts undergo an extended period of warm
      ischemia, which mandates the use of machine perfusion preservation if they are to
      be successfully recovered for transplantation. Because the minimum coronary
      artery flow needed to meet the basal oxygen demand (DCRIT) of a DCD heart during
      machine perfusion preservation is critical and yet unknown, we studied this in a
      DCD rat heart model. Adult male rats were anesthetized, intubated, heparinized,
      and paralyzed with vecuronium. The DCD hearts (n = 9) were recovered 30 minutes
      after circulatory death whereas non-DCD control hearts (n = 12) were recovered
      without circulatory death. Hearts were perfused through the aorta with an
      oxygenated Belzer Modified Machine Perfusion Solution (A3-Bridge to Life Ltd.
      Columbia, SC) at 15 degrees C or 22 degrees C starting at a flow index of 300
      ml/100 g/min and decreasing by 40 ml/100 g/min every 10 minutes. Inflow (aortic)
      and outflow (inferior vena cava) perfusate samples were collected serially to
      assess the myocardial oxygen consumption index (MVO2) and O2 extraction ratio.
      The DCRIT is the minimum coronary flow below which the MVO2 becomes flow
      dependent. The MVO2, DCRIT, and oxygen extraction ratios were higher in DCD
      hearts compared with control hearts. The DCRIT for DCD hearts was achieved only
      at 15 degrees C and was significantly higher (131.6 +/- 7 ml/100 g/min) compared
      with control hearts (107.7 +/- 8.4 ml/100 gm/min). The DCD hearts sustain warm
      ischemic damage and manifest higher metabolic needs during machine perfusion.
      Establishing adequate coronary perfusion is critical to preserving organ function
      for potential heart transplantation.

PMID- 28746081
TI  - Synergism of Electrospun Nanofibers and Pulsed Electromagnetic Field on
      Osteogenic Differentiation of Induced Pluripotent Stem Cells.
AB  - According to the current therapies failure for bone fractures and lesions, tissue
      engineering showed a great potential to help solve these challenges. Because the
      use of growth factors is very limited in the clinic, it could be very useful that
      could be introducing an alternative to it. Extremely low frequency pulsed
      electromagnetic fields (PEMF, 1 mT, 50 Hz) were used for achieving this aim. The
      PEMF potential in combination with electrospun polycaprolactone (PCL) nanofibers
      was used to investigate the osteogenic potential of human induced pluripotent
      stem cells (iPSCs). Several relevant osteogenic markers, such as Alizarin red
      staining, alkaline phosphatase activity, calcium content, gene expression, and
      immunocytochemistry, were used to evaluate osteoinductivity of PEMF. Results were
      shown that PEMF alone can induce osteogenic differentiation, but this capability
      increased when used in combination with PCL nanofibers significantly. In
      addition, simultaneous use of osteogenic medium, PEMF and PCL surprisingly
      increased osteogenic differentiation potential of iPSCs. According to the
      results, PEMF alone, iPSCs-seeded PCL, and both of them could be considered as a
      promising candidate for use in bone tissue engineering applications.

PMID- 28746082
TI  - HeartWare Ventricular Assist Device as a Bridge-to-Transplant in a Small Boy with
      Complicated Kawasaki Disease.
AB  - We report a case of HeartWare ventricular assist device (HVAD) implant as a
      Bridge-to-Transplant in the smallest and the youngest known patient, a 32-month
      old boy (body surface area of 0.66 m2) with known Kawasaki disease and giant
      coronary artery aneurysms. The disease course was complicated by coronary
      thromboembolism resulting in acute myocardial infarction, ventricular
      fibrillation, and cardiac arrest. After short-term support with extracorporeal
      membrane oxygenation for 7 days and long-term support with an HVAD for 5 months,
      he underwent heart transplantation and is doing well 2 months after the
      transplant.

PMID- 28746083
TI  - Novel Cardiac Coordinate Modeling System for Three-Dimensional Quantification of
      Inflow Cannula Malposition of HeartMate II LVADs.
AB  - Optimal function of left ventricular assist devices (LVADs) depends on proper
      alignment of the inflow cannula (IC). Quantitative guidelines for IC angulation
      are lacking because of variation in cardiac geometry and difficulty in analyzing
      three-dimensional (3D) cannula orientation relative to the left ventricle (LV).
      Based on contrast-enhanced computed tomography images from five normal and five
      clinically malpositioned IC cases in patients with HeartMate II LVADs, we
      developed a method for 3D quantification of IC malpositioning. Using Mimics image
      software (Materialise, Leuven, Belgium), the native heart, major arteries, and
      LVAD were segmented to create patient-specific 3D models, allowing LV cavity
      volume and long-axis length to be measured directly. The deviation of the IC was
      quantified in a cylindrical coordinate system at the IC insertion point relative
      to the mitral valve and septum, and IC occlusion was assessed by the distance
      between cannula inlet and the proximal endocardium. Compared with normal cases,
      patients with malpositioned pumps had shorter LV length (p = 0.03) and reduced
      pump pocket depth (p = 0.009). Malpositioned pumps may experience greater
      obstruction by the nearby myocardium. This quantitative 3D modeling tool may help
      identify different modes of pump malalignment and migration and may facilitate
      preoperative planning and minimally invasive approaches via virtual LVAD
      implantation.

PMID- 28746084
TI  - Epidemiology and location of primary retrieval missions in a Scottish aeromedical
      service.
AB  - INTRODUCTION: Prehospital critical care teams comprising an appropriately trained
      physician and paramedic or nurse have been associated with improved outcomes in
      selected trauma patients. These teams are a scarce and expensive resource,
      especially when delivered by rotary air assets. The optimal tasking of
      prehospital critical care teams is therefore vital and remains a subject of
      debate. Emergency Medical Retrieval Service (EMRS) provides a prehospital
      critical care response team to incidents over a large area of Scotland either by
      air or by road. METHODS: A convenience sample of consecutive EMRS missions
      covering a period of 18 months from May 2013 to January 2015 was taken. These
      missions were matched with the ambulance service information on geographical
      location of the incident. In order to assess the appropriateness of tasking,
      interventions undertaken on each mission were analysed and divided into two
      subcategories: 'critical care interventions' and 'advanced medical
      interventions'. A tasking was deemed appropriate if it included either category
      of intervention or if a patient was pronounced life extinct at the scene.
      RESULTS: A total of 1279 primary missions were undertaken during the study
      period. Of these, 493 primary missions met the inclusion criteria and generated
      complete location data. The median distance to scene was calculated as 5.6 miles
      for land responses and 34.2 miles for air responses. Overall, critical care
      interventions were performed on 17% (84/493) of patients. A further 21% (102/493)
      of patients had an advanced medical intervention. Including those patients for
      whom life was pronounced extinct on scene by the EMRS team, a total of 42%
      (206/493) taskings were appropriate. DISCUSSION: Overall, our data show a wide
      geographical spread of tasking for our service, which is in keeping with other
      suburban/rural models of prehospital care. Tasking accuracy is also comparable to
      the accuracy shown by other similar services.

PMID- 28746085
TI  - Impact of screening and antiretroviral therapy on anal cancer incidence in HIV
      positive MSM.
AB  - BACKGROUND: The incidence of anal cancer is high in HIV-positive MSM. We modeled
      the impact of screening strategies and combination antiretroviral therapy (cART)
      coverage on anal cancer incidence in Switzerland. METHODS: Individual-based,
      dynamic simulation model parameterized with Swiss HIV Cohort Study and literature
      data. We assumed all men to be human papillomavirus infected. CD4 cell count
      trajectories were the main predictors of anal cancer. From 2016 we modeled cART
      coverage either as below 100% (corresponding to 2010-2015) or as 100%, and the
      following four screening strategies: no screening, yearly anal cytology
      (Papanicolaou smears), yearly anoscopy and targeted anoscopy 5 years after CD4
      count dropped below 200 cells/MUl. RESULTS: Median nadir CD4 cell count of 6411
      MSM increased from 229 cells/MUl during 1980-1989 to 394 cells/MUl during 2010
      2015; cART coverage increased from 0 to 83.4%. Modeled anal cancer incidence
      peaked at 81.7/100 000 in 2009, plateaued 2010-2015 and will decrease to 58.7 by
      2030 with stable cART coverage, and to 52.0 with 100% cART coverage. With yearly
      cytology, incidence declined to 38.2/100 000 by 2030, with yearly anoscopy to
      32.8 and with CD4 cell count guided anoscopy to 51.3. The numbers needed to
      screen over 15 years to prevent one anal cancer case were 384 for yearly
      cytology, 313 for yearly anoscopy and 242 for CD4 cell count-dependent screening.
      CONCLUSION: Yearly screening of HIV-positive MSM may reduce anal cancer incidence
      substantially, with a number needed to screen that is comparable with other
      screening interventions to prevent cancer.

PMID- 28746086
TI  - HIV drug resistance in infants increases with changing prevention of mother-to
      child transmission regimens.
AB  - OBJECTIVES: The objectives of this study were to determine HIV drug resistance
      (HIVDR) prevalence in Zambian infants upon diagnosis, and to determine how
      changing prevention of mother-to-child transmission (PMTCT) drug regimens affect
      drug resistance. DESIGN: Dried blood spot (DBS) samples from infants in the
      Lusaka District of Zambia, obtained during routine diagnostic screening, were
      collected during four different years representing three different PMTCT drug
      treatment regimens. METHODS: DNA extracted from dried blood spot samples was used
      to sequence a 1493 bp region of the reverse transcriptase gene. Sequences were
      analyzed via the Stanford HIVDRdatabase (http://hivdb.standford.edu) to screen
      for resistance mutations. RESULTS: HIVDR in infants increased from 21.5 in
      2007/2009 to 40.2% in 2014. Nonnucleoside reverse transcriptase inhibitor
      resistance increased steadily over the sampling period, whereas nucleoside
      reverse transcriptase inhibitor resistance and dual class resistance both
      increased more than threefold in 2014. Analysis of drug resistance scores in each
      group revealed increasing strength of resistance over time. In 2014, children
      with reported PMTCT exposure, defined as infant prophylaxis and/or maternal
      treatment, showed a higher prevalence and strength of resistance compared to
      those with no reported exposure. CONCLUSION: HIVDR is on the rise in Zambia and
      presents a serious problem for the successful lifelong treatment of HIV-infected
      children. PMTCT affects both the prevalence and strength of resistance and
      further research is needed to determine how to mitigate its role leading to
      resistance.

PMID- 28746087
TI  - Assisted partner services for HIV: ready to go global.

PMID- 28746088
TI  - The harms of HIV criminalization: responding to the 'association of HIV diagnosis
      rates and laws criminalizing HIV exposure in the United States'.

PMID- 28746089
TI  - Dolutegravir-based regimen maintains virological success in a patient with
      archived mutations to integrase inhibitors.

PMID- 28746094
TI  - Putting ethics into action.

PMID- 28746095
TI  - A nursing protocol for safe IVIG administration.

PMID- 28746098
TI  - Inguinal hernia: A battle of the bulge.

PMID- 28746096
TI  - Teaching compassion for impoverished patients through simulation.

PMID- 28746099
TI  - Encouraging new nurse authorship.

PMID- 28746100
TI  - Medicinal cannabis: A primer for nurses.

PMID- 28746101
TI  - Mammalian meat allergy: Unexpected danger.

PMID- 28746102
TI  - Nurse-to-patient etiquette: It's more than good manners.

PMID- 28746103
TI  - Can direct oral anticoagulants be reversed?

PMID- 28746104
TI  - West Nile virus.

PMID- 28746105
TI  - Ensuring safe discharge with a standardized checklist and discharge pause.

PMID- 28746106
TI  - Documentation drivers for optimal patient outcomes.

PMID- 28746107
TI  - Combination cardiovascular drugs.

PMID- 28746108
TI  - Online resources for gerontology.

PMID- 28746110
TI  - Managing delirium behaviors with one-to-one sitters.

PMID- 28746111
TI  - REVISITING THE PAST AND ENJOYING THE PRESENT.

PMID- 28746112
TI  - Patient Education and Discharge Planning to Prevent Functional Decline in the
      Older Adult.
AB  - The population in the United States is aging, and persons older than 65 years
      account for over 50% of healthcare costs. Preventing functional decline in older
      adults through patient education and optimal discharge planning is one way we can
      succeed in decreasing healthcare costs, readmissions, and mortality in this
      population. The aim of this article is to present viable healthcare policy
      options to prevent or minimize functional decline in the older adult, regardless
      of what health-related facility the person enters. Policy objectives include
      mandating functional screening tests on all persons 65 years and older,
      addressing functional status as a required element of discharge planning,
      tracking and reporting patient outcomes, and utilizing advanced practice nurses
      to the full extent of their education and scope of practice. Three policy options
      are presented, analyzed, and compared. The summary concludes with a recommended
      policy option.

PMID- 28746113
TI  - Effects of Hot Packs on Small-Intestinal Motility Measured by Doppler Ultrasound
      and Subjective Feelings in Normal Adults.
AB  - Constipation is a common problem in patients and the general population. Hot
      packs can relieve constipation, but the effect on small-intestinal motility
      remains unknown. We aimed to determine the effect of hot packs on small
      intestinal motility and subjective feelings associated with bowel activity after
      removing the hot packs. Thirty-four normal adults were assigned to either an
      experimental group (n = 18) or a control group (n = 16). Hot and normal packs
      were applied for 10 minutes to the lumbar regions of the experimental and control
      groups, respectively. Small-intestinal motility was measured by Doppler
      ultrasound before, during, and after pack application. Subjective feelings were
      also evaluated after removing the packs. The number of small-intestinal
      peristalses and subjective feelings of 20 participants showing anechoic areas in
      the small-intestinal lumen were analyzed.

PMID- 28746114
TI  - Differences Across Illness Perceptions in Inflammatory Bowel Disease and Their
      Relationships to Psychological Distress and Quality of Life.
AB  - Patients with greater inflammatory bowel disease activity readily identify poorer
      psychosocial outcomes; however, the role of gender, disease type, and individual
      illness perceptions facets are less well known. This study aimed to characterize
      the role of illness perceptions, gender, and disease type on anxiety, depression,
      and quality of life. Eighty-one patients diagnosed with inflammatory bowel
      disease (39 men, mean age 35 years) attending a tertiary hospital outpatient
      clinic were studied. Questionnaires used included the Manitoba Index, the Brief
      Illness Perceptions Questionnaire, Hospital Anxiety and Depression Scale, and the
      World Health Organization Brief Quality of Life Scale. Female patients with
      active disease tended to report increased anxiety, depression, and reduced
      quality of life. Regarding illness perceptions, patients with Crohn disease
      reported significantly more concerns about its chronicity, while female patients
      reported being significantly more concerned about the impact of their illness on
      identity, chronicity, overall concern, and having a greater emotional impact.
      Hierarchical regression indicated that 36% of depression, 42% of anxiety, and 57%
      of quality of life could be accounted for by disease activity and type, gender,
      and illness perceptions. The findings suggest that in addition to a patient's
      perceived disease status, gastroenterology nurses should also be aware that
      patient gender and their perceptions of illness play a significant impact not
      only on anxiety and depression but also on quality of life. Increased disease
      activity is associated with more severe anxiety and depression and reduced
      quality of life. Female patients are also at a greater risk of reporting negative
      illness perceptions and increased levels of anxiety, depression, and lower
      quality of life.

PMID- 28746115
TI  - Comparison of Two Different Methods for the Measurement of Gastric Residual
      Volume.
AB  - The objective of this study was to determine the difference between gastric
      residual volume measurements without giving air compared to giving 30 ml of air
      via the feeding tube. This experimental study was on 60 subjects fed enterally at
      a university hospital. Data collection was with the 12-item "Gastric Residual
      Volume Measurement Instructions" and "Gastric Residual Volume Observation Form."
      The same subjects composed experimental and control groups. Gastric residual
      volume measurements were taken before feedings at 10:00 a.m., 1:00 p.m., and 4:00
      p.m. with a 60-ml syringe. First measurement was taken without giving air by
      withdrawing the syringe piston at 2-3 ml/second. Second measurement was applied
      by giving 30 ml of air and withdrawing the piston at the same speed. Student's t
      test was used for data analysis. A total of 180 measurements were made for each
      method. Gastric residual volume averages were 3.71 +/- 7.97 ml without air and
      3.78 +/- 8.08 ml with air. The difference between averages was statistically
      significant (p < .05). Difficulties withdrawing the syringe piston without giving
      air occurred in 85% of the intermittently enterally fed patients and 22.8% of
      those fed continuously. Gastric residual volume measurements with air were higher
      than those without air. The aspiration procedure with air was easier. Gastric
      residual volume measurements should be made with 30 ml of air and by withdrawing
      the syringe piston at 2-3 ml/minute.

PMID- 28746116
TI  - Falls in Patients With Liver Cirrhosis.

PMID- 28746117
TI  - Functional Gastrointestinal Disorders Common Among Nurses With Poor Sleep Quality
      in Shanghai, China: A Pilot Study.
AB  - This study aimed to determine whether functional gastrointestinal disorders are
      more common among nurses with self-reported poor sleep. In total, 468 nurses
      working the day shift or rotating shifts completed two questionnaires: the
      questionnaire for irritable bowel syndrome (IBS) using Rome III criteria and the
      Pittsburgh Sleep Quality Index (PSQI). The prevalence of poor sleep was 41.04%
      (95% confidence interval, CI: [36.23, 45.85]), and poor sleep was significantly
      more common among rotating-shift nurses than among day-shift nurses (50.70% vs.
      29.95%; p < .05). Among nurses with poor sleep, the prevalence of IBS and
      functional constipation was 35.15% (95% CI: [27.86, 42.44]) and 11.52% (95% CI:
      [6.65, 16.39]), respectively. After adjusting for age, work schedule, night pain,
      and psychological factors, IBS (odds ratio, OR: 1.88; 95% CI: [1.03, 2.49]) and
      functional constipation (OR: 1.77; 95% CI: [0.64, 2.57]) were significantly more
      common in nurses with poor sleep. We conclude that IBS and functional
      constipation are prevalent in nurses with poor sleep. Poor sleep was
      independently associated with IBS and functional constipation among nurses in
      Shanghai, China.

PMID- 28746118
TI  - ILEUS DUE TO EXTENSIVE AIR INSUFFLATION WITH ENDOSCOPIC RETROGRADE CHOLANGIO
      PANCREATOGRAPHY.

PMID- 28746119
TI  - BEZLOTOXUMAB: A NEW DRUG FOR THE TOXIC EFFECTS OF CLOSTRIDIUM DIFFICILE.

PMID- 28746120
TI  - Bezlotoxumab: A New Drug for the Toxic Effects of Clostridium Difficile.

PMID- 28746121
TI  - Development of a prognostic nomogram for cirrhotic patients with upper
      gastrointestinal bleeding.
AB  - BACKGROUND AND AIM: Upper gastrointestinal bleeding (UGIB) is a complication with
      a high mortality rate in critically ill patients presenting with cirrhosis.
      Today, there exist few accurate scoring models specifically designed for
      mortality risk assessment in critically ill cirrhotic patients with upper
      gastrointestinal bleeding (CICGIB). Our aim was to develop and evaluate a novel
      nomogram-based model specific for CICGIB. PATIENTS AND METHODS: Overall, 540
      consecutive CICGIB patients were enrolled. On the basis of Cox regression
      analyses, the nomogram was constructed to estimate the probability of 30-day, 90
      day, 270-day, and 1-year survival. An upper gastrointestinal bleeding-chronic
      liver failure-sequential organ failure assessment (UGIB-CLIF-SOFA) score was
      derived from the nomogram. Performance assessment and internal validation of the
      model were performed using Harrell's concordance index (C-index), calibration
      plot, and bootstrap sample procedures. UGIB-CLIF-SOFA was also compared with
      other prognostic models, such as CLIF-SOFA and model for end-stage liver disease,
      using C-indices. RESULTS: Eight independent factors derived from Cox analysis
      (including bilirubin, creatinine, international normalized ratio, sodium,
      albumin, mean artery pressure, vasopressin used, and hematocrit decrease>10%)
      were assembled into the nomogram and the UGIB-CLIF-SOFA score. The calibration
      plots showed optimal agreement between nomogram prediction and actual
      observation. The C-index of the nomogram using bootstrap (0.729; 95% confidence
      interval: 0.689-0.766) was higher than that of the other models for predicting
      survival of CICGIB. CONCLUSION: We have developed and internally validated a
      novel nomogram and an easy-to-use scoring system that accurately predicts the
      mortality probability of CICGIB on the basis of eight easy-to-obtain parameters.
      External validation is now warranted in future clinical studies.

PMID- 28746122
TI  - Anterior and Posterior Vertebral Column Resection Versus Posterior-only
      Technique: A Comparison of Clinical Outcomes and Complications in Congenital
      Kyphoscoliosis.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: The purpose of this study is to
      compare the anterior-posterior surgery to posterior-only vertebra resection for
      congenital kyphoscoliosis in pediatric patients. SUMMARY OF BACKGROUND DATA:
      Vertebral column resection is a very powerful correction technique mainly used in
      the treatment of severe and rigid spinal deformities. The technique can be
      applied with combined anterior and posterior vertebral column resection (APVCR)
      or posterior-only vertebral column resection (PVCR) approaches. PVCR has gained
      popularity recently due to several apparent advantages, but APVCR is still
      believed by some to be a viable alternative, despite the use of an anterior
      exposure. MATERIALS AND METHODS: A retrospective chart and radiographic review
      was performed including the patients with congenital kyphoscoliosis up to 16
      years of age who were operated on by a single senior surgeon in our department
      after 2005. The data included surgical time, estimated blood loss, duration of
      hospital and postoperative intensive care unit stay, intraoperative and
      postoperative complications. Preoperative, postoperative, and follow-up
      radiographs were evaluated for scoliosis, kyphosis, and spinal balance. RESULTS:
      Twenty-six patients (20 girls, 6 boys) met the inclusion criteria. APVCR was
      performed on 17 (median age, 13.2 y) and PVCR on 9 (median age, 10.7 y).
      Scoliosis correction at the time of last follow-up was 54.3% and 52.6% for APVCR
      and PVCR, respectively, whereas the average kyphosis correction was 25.4 degrees
      in APVCR and 30.1 degrees in PVCR group. Surgical time, hospital stay, and
      estimated blood loss were all significantly higher in the APVCR group, whereas
      the complication rates were similar. No neurological or vascular complications
      were encountered. CONCLUSIONS: This study showed that although the operative time
      and surgical blood loss were higher with APVCR, there were no major complications
      and the radiologic outcomes were similar between APVCR and PVCR. APVCR should be
      considered as an acceptable technique especially in deformities where PVCR would
      be technically difficult or at the beginning of the spine surgeon's learning
      curve. LEVEL OF EVIDENCE: Level III.

PMID- 28746123
TI  - A Change in Lumbar Sagittal Alignment After Single-level Anterior Lumbar
      Interbody Fusion for Lumbar Degenerative Spondylolisthesis With Normal Sagittal
      Balance.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: The object is to assess the
      correlation between whole lumbar lordosis (LL) and the segmental angle (SA) after
      single-level anterior lumbar interbody fusion for degenerative lumbar
      spondylolisthesis. SUMMARY OF BACKGROUND DATA: The restoration of the SA at lower
      lumbar spine is meaningful, considering it contributes approximately 60% of LL,
      and revision surgery due to flat back or adjacent segment pathology was necessary
      decades after the initial surgery. However, little is known about the change of
      whole lumbar curvature after single-level lower lumbar fusion surgery, especially
      for balanced spine. MATERIALS AND METHODS: We included 41 consecutive patients
      (M:F=9:32; mean age, 59.8+/-9.3 y) with a single-level anterior lumbar interbody
      fusion surgery for low-grade degenerative spinal spondylolisthesis, with C7 plumb
      line of <5 cm and >=2-year follow-up period. The operated levels were L4-L5 in 34
      patients and L5-S1 in 7 patients. Whole LL, SA, pelvic tilt, and sacral slope
      were compared. RESULTS: According to the Macnab criteria, a favorable outcome
      (excellent, 21; good, 15) was achieved in 36/41 (88%; excellent, 21; good, 15)
      patients. LL and SA were significantly changed from -50.8+/-9.9 to -54.6+/-11.1
      degrees and -15.6+/-6.1 to -18.7+/-5.1 degrees (P<0.01), and a positive
      correlation (r=0.43, P=0.01) was observed between LL and SA at postoperative
      month 24. The changes to the pelvic tilt and sacral slope were not significant.
      CONCLUSIONS: Whole lumbar sagittal alignment was influenced by single SA.
      Therefore, obtaining adequate segmental lordosis is desirable considering the
      effect on the whole spine for a long time.

PMID- 28746124
TI  - A Japanese Stretching Intervention Can Modify Lumbar Lordosis Curvature.
AB  - STUDY DESIGN: Eighteen healthy male adults were assigned to either an
      intervention or control group. OBJECTIVES: Isogai dynamic therapy (IDT) is one of
      Japanese stretching interventions and has been practiced for over 70 years.
      However, its scientific quantitative evidence remains unestablished. The
      objective of this study was to determine whether IDT could modify lumbar
      curvature in healthy young adults compared with stretching exercises used
      currently in clinical practice. SUMMARY OF BACKGROUND DATA: None of previous
      studies have provided data that conventional stretching interventions could
      modify spinal curvatures. However, this study provides the first evidence that a
      specific form of a Japanese stretching intervention can acutely modify the spinal
      curvatures. METHODS: We compared the effects of IDT, a Japanese stretching
      intervention (n=9 males), with a conventional stretching routine (n=9 males) used
      widely in clinics to modify pelvic tilt and lumbar lordosis (LL) angle. We
      measured thoracic kyphosis (TK) and LL angles 3 times during erect standing using
      the Spinal Mouse before and after each intervention. IDT consisted of: (1) hip
      joint correction, (2) pelvic tilt correction, (3) lumbar alignment correction,
      and (4) squat exercise stretch. The control group performed hamstring stretches
      while (1) standing and (2) sitting. RESULTS: IDT increased LL angle to 25.1
      degrees (+/-5.9) from 21.2 degrees (+/-6.9) (P=0.047) without changing TK angle
      (pretest: 36.8 degrees [+/-6.9]; posttest: 36.1 degrees [+/-6.5]) (P=0.572). The
      control group showed no changes in TK (P=0.819) and LL angles (P=0.744).
      CONCLUSIONS: IDT can thus be effective for increasing LL angle, hence anterior
      pelvic tilt. Such modifications could ameliorate low back pain and improve
      mobility in old adults with an unfavorable pelvic position.

PMID- 28746125
TI  - Comparison of Pedicle Screw Fixation Strength Among Different Transpedicular
      Trajectories: A Finite Element Study.
AB  - STUDY DESIGN: Comparative biomechanical study by finite element (FE) method.
      OBJECTIVE: To investigate the pullout strength of pedicle screws using different
      insertional trajectories. SUMMARY OF BACKGROUND DATA: Pedicle screw fixation has
      become the gold standard for spinal fusion, however, not much has been done to
      clarify how the fixation strength of pedicle screws are affected by insertional
      trajectories and bone properties. MATERIALS AND METHODS: Three-dimensional FE
      models of 20 L4 vertebrae were constructed from the computed tomographic data.
      Five different transpedicular trajectories were compared: the traditional
      trajectory, the vertical trajectory, and the 3 lateral trajectories with
      different sagittal directions (caudal, parallel, cranial). For a valid
      comparison, screws of the same shape and size were inserted into the same pedicle
      in each subject, and the pullout strength were compared with nonlinear FE
      analyses. In addition, the pullout strength was correlated with bone mineral
      density (BMD). RESULTS: The mean pullout strength showed a 3.9% increase for the
      vertical trajectory relative to the traditional trajectory, 6.1% for the lateral
      caudal trajectory, 21.1% for the lateral-parallel trajectory, and 34.7% for the
      lateral-cranial trajectory. The lateral-cranial trajectory demonstrated the
      highest value among all trajectories (P<0.001). In each trajectory, the
      correlation coefficient between the pullout strength and BMD of the femoral neck
      (r=0.74-0.83, P<0.01) was higher than the mean BMD of all the lumbar vertebrae
      (r=0.49-0.75, P<0.01), BMD of the L4 vertebra (r=0.39-0.64, P<0.01), and regional
      BMD of the L4 pedicle (r=0.53-0.76, P<0.01). CONCLUSIONS: Regional variation in
      the vertebral bone density and the amount of denser bone-screw interface
      contribute to the differences of stiffness among different screw trajectories.
      BMD of the femoral neck is considered to be a better objective predictor of
      pedicle screw stability than that of the lumbar vertebra.

PMID- 28746126
TI  - Kirschner Wire and Bone Cement is a Viable Alternative to Reconstruction of Large
      Iliac Bone Defects After Strut Bone Graft Harvesting.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To assess the safety and efficacy
      of iliac crest defect reconstruction using Kirschner wire (K
      wire)/polymethylmethacrylate (PMMA) versus traditional autologous rib graft
      reconstruction. SUMMARY OF BACKGROUND DATA: The iliac crest has been the
      preferred donor site for strut bone graft for various spinal fusion surgeries.
      METHODS: Seventy-three patients (44 males and 29 females; average age: 57.2 y)
      were divided into 2 groups: the rib group (35 patients) and the K-wire/PMMA group
      (38 patients). All operations involved anterior spinal interbody fusion. Patients
      were followed-up, on average, for 34.2 months using plain radiographs and both
      pain and cosmesis visual analog scales (VAS) to assess the clinical results after
      surgery. RESULTS: Almost all patients had pain VAS scores of <=1 and grade 1
      cosmesis VAS scores with no significant difference between the 2 groups in terms
      of either pain or cosmesis (P=1.00 and 0.505, respectively). In addition, few
      complications were noted in both groups. Radiographic complications in the rib
      group and the K-wire group numbered 4 (11%) and 2 (5%), respectively; however,
      did not significantly differ between the 2 groups (P=0.418). One case required
      intraoperative revision of the length of the K-wire and 1 case needed reoperation
      for iliac ring fracture and K-wire migration. An additional case required
      revision due to a bad fall. CONCLUSIONS: K-wire and bone cement reconstruction is
      an effective and safe alternative method for large iliac bone defect repair when
      autologous rib graft is not available.

PMID- 28746127
TI  - Dysphagia After Occipitothoracic Fusion is Caused by Direct Compression of
      Oropharyngeal Space Due to Anterior Protrusion of Mid-cervical Spine.
AB  - STUDY DESIGN: This was a retrospective study. OBJECTIVE: To investigate the
      relationship among the craniocervical alignment, the oropharyngeal space, and the
      incidence of dysphagia after occipitothoracic fusion (OTF). SUMMARY OF BACKGROUND
      DATA: Craniocervical malalignment after OTF is one of a trigger of dysphagia.
      However, there has been no logical explanation for the etiology yet. METHODS: A
      total of 32 patients who underwent OTF (5 male, 27 female) were reviewed.
      Following 4 parameters on the lateral cervical radiogram, pharyngeal tilt angle
      (PTA); the angle between the McGregor's line and the line that links the center
      of C2 pedicle and the center of vertebral body at the apex of cervical sagittal
      curvature, diameter of oropharyngeal airway space (dPS), O-C2 angle, and C2-C7
      angle were measured at follow-up and then the relationship of these parameters
      and their influence to the incidence of dysphagia were analyzed. RESULTS: Six of
      32 cases (18.8%) exhibited postoperative dysphagia. ROC curves showed that PTA
      and dPS had moderate accuracy for the predictor of the dysphagia after OTF with
      the area under the curve (AUC) of 0.76 and 0.86 respectively, whereas O-C2 angle
      had low accuracy with AUC of 0.69 and C2-C7 angle was almost useless for
      prediction of postoperative dysphagia with AUC of 0.51. A multiple linear
      regression analysis showed that only PTA was significantly correlated with dPS
      (beta=0.822, P=0.014), whereas the O-C2 angle (beta=0.101, P=0.779) and C2-C7
      angle (beta=0.352, P=0.157) had negligibly small influence on dPS. CONCLUSIONS:
      Our results demonstrated strong relationships between PTA and the value of dPS,
      and the incidence of dysphagia. As PTA reflects anterior protrusion of mid
      cervical spine, these results indicated that dysphagia after OTF is caused by
      narrowing of oropharyngeal space due to direct compression from anteirorly
      protruded mid-cervical spine.

PMID- 28746128
TI  - Does the Position of the Aorta Change With the Altered Body Position in
      Ankylosing Spondylitis Patients With Thoracolumbar Kyphosis?: A Magnetic
      Resonance Imaging Investigation.
AB  - STUDY DESIGN: A prospective magnetic resonance imaging study. OBJECTIVE: To
      quantitatively explore the differences in the anatomic position of the aorta
      relative to the spine between supine and prone positions in ankylosing
      spondylitis (AS) patients with thoracolumbar kyphosis. SUMMARY OF BACKGROUND
      DATA: Aortic complications may occur during the lumbar spine osteotomy in
      correcting thoracolumbar kyphosis secondary to AS, and a clear understanding of
      the spatial relationship between the aorta and the vertebrae is essential to
      prevent these iatrogenic complications. However, previous anatomic study was
      performed with AS patients in the supine position, which was different from the
      prone position adopted in surgery. To date, no report has been published to
      investigate the mobility of the aorta relative to the vertebrae between supine
      and prone positions in AS patients with thoracolumbar kyphosis. MATERIALS AND
      METHODS: From March 2013 to September 2014, 22 AS patients (21 males, 1 female)
      with thoracolumbar kyphosis with a mean age of 30.7 years (range, 19-46 y) were
      recruited. Magnetic resonance imaging examinations from T9 to L3 in both the
      supine and prone positions were performed, and the left pedicle-aorta (LtP-Ao)
      angle and LtP-Ao distance were measured at each level. The differences of these
      parameters between the 2 positions were compared by the paired sample t test, and
      the relationships between the shifting of the aorta and the change of global
      kyphosis and lumbar lordosis were evaluated by the Pearson correlation
      coefficient. The level of significance (alpha) was set at 0.05. RESULTS: At T9-L3
      levels, no significant difference was noted in LtP-Ao distances (43.78 vs. 44.42
      mm; P=0.077) and LtP-Ao angles (0.82 vs. 0.22 degrees; P=0.053) between supine
      and prone positions. The correlation analysis also revealed no remarkable
      correlation between the change of LtP-Ao angle and increase of global kyphosis
      and lumbar lordosis in the prone position. CONCLUSIONS: There is no significant
      change of the relative positions between the aorta and the vertebrae at T9-L3
      levels after the patient turned to a prone position, which implied that the
      mobility and range of motion of the aorta is limited in advanced stage of AS.

PMID- 28746129
TI  - Comparison of Posterior Lumbar Interbody Fusion Versus Posterolateral Fusion for
      the Treatment of Isthmic Spondylolisthesis.
AB  - STUDY DESIGN: Systematic review and meta-analysis. BACKGROUND: Posterolateral
      fusion (PLF) and posterior lumbar interbody fusion (PLIF) were widely used in the
      treatment of lumbar isthmic spondylolisthesis (IS). There was a great controversy
      over the preferred fusion method. OBJECTIVE: The purpose of this study is to
      evaluate the clinical outcomes between PLF and PLIF for the treatment of IS.
      MATERIALS AND METHODS: Related studies that compared the clinical effectiveness
      of PLIF and PLF for the treatment of IS were acquired by a comprehensive search
      in 4 electronic databases (PubMed, EMBASE, Cochrane Controlled Trial Register,
      and MEDLINE) from January 1950 through December 2014. Included studies were
      performed according to eligibility criteria. The main endpoints included:
      improvement of clinical satisfaction, complication rate, reoperation rate, fusion
      rate, and reoperation rate. RESULTS: A total of 9 studies were included in the
      meta-analysis; 6 were low-quality evidence and 2 were high-quality evidence as
      indicated by the Jadad scale. Compared with PLIF, PLF patients showed lower
      fusion rates [P=0.005, odds ratio (OR)=0.29 (0.14, 0.58)] and shorter operation
      times [P<0.00001, weighted mean difference (WMD)=-0.5(-0.61, -0.39)]. No
      significant difference was found in the term of postoperative visual analogue
      scale leg score [P=0.92, WMD=0.02 (-0.39, 0.44)] and visual analogue scale back
      score [P=0.41, WMD=0.20 (-0.28, 0.68)], blood loss [P=0.39, WMD=121.17 (-152.68,
      395.01)], complication rate [P=0.42, OR=1.50 (0.56, 4.03)], postoperative
      Oswestry Disability Index [P=0.3, WMD=1.09 (-0.97, 3.15)], and postoperative
      clinical satisfaction [P=0.84, OR=1.06 (0.60, 1.86)]. CONCLUSIONS: In conclusion,
      our meta-analysis suggested that PLF shows significant lower fusion rate compared
      with PLIF. Although PLIF had more operation time than PLF, there was no
      significant difference in global assessment of clinical outcome between the 2
      fusion procedures. However, future well-designed, randomized-controlled trials
      are still needed to further confirm our results.

PMID- 28746130
TI  - Can MRI Predict Flexibility in Scheuermann Kyphosis Patients?
AB  - STUDY DESIGN: Retrospective, blinded analysis of imaging studies. OBJECTIVE: The
      aim of this study is compare the use of magnetic resonance imaging (MRI) to
      lateral radiograph using bolster in the evaluation of Scheuermann kyphosis (SK)
      curve flexibility measurement. SUMMARY AND BACKGROUND DATA: The flexibility of
      the thoracic curve [thoracic kyphosis (TK)] in SK is of primary importance in its
      preoperative planning. Several methods have been described for SK curve
      flexibility measurement. The most commonly used method is lateral hyperextension
      radiography on hard bolster [hyperextension radiograph (HE)]. No current methods
      use MRI for flexibility assessment. MATERIALS AND METHODS: Flexibility of TK in
      SK patients was measured as a difference between standing radiograph and bolster
      assisted lateral HE or supine MRI. The sagittal Cobb angle of the TK was measured
      between the superior endplate of T4 and the inferior endplate of T12 vertebral
      body. Flexibilities measured by these 2 methods were compared and analyzed using
      the generalized estimating equation analysis and the correlation analysis.
      RESULTS: We assessed 18 SK patients (14 males and 4 females) with mean age of
      20.06+/-6.03 years. The standing TK x-rays showed 83.8+/-6.1 degrees. On HE, TK
      curve reduced by 39.3 degrees (95% confidence interval, 35.8-42.9) to 44.5+/-6.2
      degrees (P<0.001). Preoperative MRI images showed TK of 53.8+/-5.9 degrees which
      means reduction by 30 degrees (95% confidence interval, 26.6-33.4) from the
      standing radiographs (P<0.001). Linear dependency between HE and MRI flexibility
      with a mean difference of 9.3 degrees was found (R=0.61, P<0.001). CONCLUSIONS:
      Our study shows that preoperative MRI can be used for SK flexibility assessment
      with similar predictive value as routinely used bolster-assisted hyperextension
      lateral radiograph. Consequently, patient exposure to preoperative hyperextension
      ionizing radiation may be reduced.

PMID- 28746131
TI  - Assessment of the Cross-Sectional Areas of the Psoas Major and Multifidus Muscles
      in Patients With Adult Spinal Deformity: A Case-Control Study.
AB  - STUDY DESIGN: This is a case-control study. OBJECTIVE: The present study aimed to
      compare the cross-sectional areas of the psoas major and multifidus muscles
      between elderly patients with adult spinal deformity (ASD) and age-matched and
      body weight-matched controls, and to evaluate the associations between the cross
      sectional areas of these muscles and the severity of spinal deformity. SUMMARY OF
      BACKGROUND DATA: The study included 49 female kyphosis patients with mild
      scoliosis (Cobb angle <20 degrees; mean age, 70.9 y, group D). The control group
      (group C) included age-matched and body weight-matched female patients who
      underwent abdominal surgery (n=98; mean age, 71.7 y). MATERIALS AND METHODS: The
      cross-sectional areas of the bilateral psoas majors and multifidus muscles were
      calculated using preoperative L4/L5 axial computed tomography images. In group D,
      the following spinopelvic parameters were assessed: sagittal vertical axis,
      pelvic tilt, pelvic incidence, lumbar lordosis, and thoracic kyphosis. The
      relationships between the muscle cross-sectional areas and spinopelvic parameters
      were evaluated. RESULTS: The cross-sectional area of the multifidus muscle was
      lower in group D than in group C. However, the cross-sectional area of the psoas
      major muscle was not different between the 2 groups. In multiple regression
      analysis, the cross-sectional area of the multifidus muscle was significantly
      associated with all spinopelvic parameters. CONCLUSIONS: The cross-sectional area
      of the multifidus muscle might be lower in elderly patients with ASD than in
      controls. In the elderly population, the severity of sagittal spinal deformity
      might be correlated with the cross-sectional area of the multifidus muscle.
      Therefore, muscle imbalances between the flexors and extensors of the spine could
      participate in the pathology of ASD.

PMID- 28746132
TI  - Three-dimensional Cross-Platform Planning for Complex Spinal Procedures: A New
      Method Adaptive to Different Navigation Systems.
AB  - STUDY DESIGN: A feasibility study. OBJECTIVE: To develop a method based on the
      DICOM standard which transfers complex 3-dimensional (3D) trajectories and
      objects from external planning software to any navigation system for planning and
      intraoperative guidance of complex spinal procedures. SUMMARY OF BACKGROUND DATA:
      There have been many reports about navigation systems with embedded planning
      solutions but only few on how to transfer planning data generated in external
      software. MATERIALS AND METHODS: Patients computerized tomography and/or magnetic
      resonance volume data sets of the affected spinal segments were imported to Amira
      software, reconstructed to 3D images and fused with magnetic resonance data for
      soft-tissue visualization, resulting in a virtual patient model. Objects needed
      for surgical plans or surgical procedures such as trajectories, implants or
      surgical instruments were either digitally constructed or computerized tomography
      scanned and virtually positioned within the 3D model as required. As crucial step
      of this method these objects were fused with the patient's original diagnostic
      image data, resulting in a single DICOM sequence, containing all preplanned
      information necessary for the operation. By this step it was possible to import
      complex surgical plans into any navigation system. RESULTS: We applied this
      method not only to intraoperatively adjustable implants and objects under
      experimental settings, but also planned and successfully performed surgical
      procedures, such as the percutaneous lateral approach to the lumbar spine
      following preplanned trajectories and a thoracic tumor resection including
      intervertebral body replacement using an optical navigation system. To
      demonstrate the versatility and compatibility of the method with an entirely
      different navigation system, virtually preplanned lumbar transpedicular screw
      placement was performed with a robotic guidance system. CONCLUSIONS: The
      presented method not only allows virtual planning of complex surgical procedures,
      but to export objects and surgical plans to any navigation or guidance system
      able to read DICOM data sets, expanding the possibilities of embedded planning
      software.

PMID- 28746133
TI  - The Impact of a National Faculty Development Program Embedded Within an Academic
      Professional Organization.
AB  - A sizeable literature describes the effectiveness of institution-based faculty
      development programs in nurturing faculty educators as scholars, but national
      programs are less common and seldom evaluated. To fill this role, the Educational
      Scholars Program (ESP) was created within the Academic Pediatric Association
      (APA) in 2006. It is a national, three-year, cohort-based certification program
      focused on fostering educational scholarship. This article describes the
      development and outcomes of an innovative program embedded within the framework
      of a national professional organization, and offers a model for potential
      adaptation by similar organizations to enhance their support of educators.After
      10 years, 171 scholars have enrolled in the ESP, and 50 faculty have
      participated. Scholars are assigned a faculty advisor and participate in three
      full-day sessions at a national meeting; online, interactive learning modules;
      and a mentored, scholarly project. The program receives support from the APA in
      four organizational frames: structural, human resource, political, and symbolic.
      The self-perceived scholarly proficiency of the scholars in Cohort 1 increased
      significantly over time, and their productivity and collaborations increased
      during and after the program. Scholars wrote enthusiastically about their
      experience in yearly and postprogram evaluations. In interviews, eight past APA
      presidents explained that the ESP strengthened the APA's mission, created new
      leaders, and provided a new model for other APA programs. Outcomes of the ESP
      suggest that a longitudinal faculty development program embedded within a
      national professional organization can create a social enterprise not only within
      the organization but also within the broader national community of educator
      scholars.

PMID- 28746134
TI  - The MD-MEd Joint-Degree Program at Vanderbilt University: Training Future Expert
      Medical Educators.
AB  - PROBLEM: Some medical students are drawn to medical education as an area of
      academic specialization. However, few options exist for medical students who wish
      to build a scholarly foundation for future careers in medical education.
      APPROACH: In 2011, Vanderbilt University School of Medicine (VUSM) and Peabody
      College of Education and Human Development at Vanderbilt University partnered to
      establish a novel dual-degree program that, through transfer of credit, allows
      students to graduate with both an MD and a master of education (MEd) degree in
      five years. The MD-MEd joint-degree program equips students with robust knowledge
      and skills related to general education while providing opportunities through
      independent studies and capstone projects to contextualize these ideas in medical
      education. OUTCOMES: This innovation at Vanderbilt University demonstrates the
      feasibility of an MD-MEd joint-degree program. MD-MEd graduates' demonstrated
      commitment to medical education and credentials will allow them to take on
      greater educational responsibilities earlier in their careers and quickly gain
      experience. The three author participants feel their experiences allowed them to
      achieve desired competencies as educators. They have each gained early experience
      by chairing the Student Curriculum Committee and contributing to major curricular
      reform at VUSM. NEXT STEPS: The authors plan to integrate specific medical
      education competencies into the program, which will require MD-MEd students to
      develop and demonstrate proficiency in the knowledge and skills expected of
      dedicated medical educators. Graduates' career trajectories will be tracked to
      explore whether they become medical educators, conduct educational research, and
      assume leadership positions.

PMID- 28746135
TI  - Encouraging Student Interest in Teaching Through a Medical Student Teaching
      Competition.
AB  - PROBLEM: Clinician educators have realized the value not only of assigning
      teaching roles to medical students but also of offering explicit training in how
      to teach effectively. Despite this interest in the development of medical
      students' teaching skills, formal teaching instruction and opportunities for
      practice are lacking. APPROACH: To encourage medical student interest in
      teaching, the authors developed and implemented a medical student teaching
      competition (MSTC) at Emory University School of Medicine during the summers of
      2014, 2015, and 2016. Each year, eight student finalists were each paired with a
      physician "teaching coach" and given one month to prepare for the MSTC. During
      the competition, each finalist delivered an eight-minute presentation to a panel
      of seven physician and resident judges. The authors describe the development,
      implementation, and assessment of the MSTC. OUTCOMES: Approximately 150 medical
      students and faculty members attended the MSTC each year. The students in
      attendance felt that the MSTC made them more likely to seek out opportunities to
      learn how to teach effectively and to practice teaching. Additionally, some
      students are now more interested in learning about a career in academic medicine
      than they were before the MSTC. NEXT STEPS: Given the need for more formal
      initiatives dedicated to improving the teaching skills of doctors-in-training,
      including medical students, innovative solutions such as the MSTC may enhance a
      medical school's existing curriculum and encourage student interest in teaching.
      The MSTC model may be generalizable to other medical schools.

PMID- 28746136
TI  - Using Organizational Philosophy to Create a Self-Sustaining Compensation Plan
      Without Harming Academic Missions.
AB  - PROBLEM: Academic physician reimbursement has moved to productivity-based
      compensation plans. To be sustainable, such plans must be self-funding.
      Additionally, unless research and education are appropriately valued, faculty
      involved in these efforts will become disillusioned, yet revenue generation in
      these activities is less robust than for clinical care activities. APPROACH:
      Faculty at the Department of Medicine, University of Florida Health, elected a
      committee of junior and senior faculty and division chiefs to restructure the
      compensation plan in fiscal year (FY) 2011. This committee was charged with
      designing a new compensation plan based on seven principles of organizational
      philosophy: equity, compensation coupled to productivity, authority aligned with
      responsibility, respect for all academic missions, transparency, professionalism,
      and self-funding in each academic mission. OUTCOMES: The new compensation plan
      was implemented in FY2013. A survey administered at the end of FY2015 showed that
      61% (76/125) of faculty were more satisfied with this plan than the previous
      plan. Since the year before implementation, clinical relative value units per
      faculty increased 7% (from 3,458 in FY2012 to 3,704 in FY2015, P < .002),
      incentives paid per faculty increased 250% (from $3,191 in FY2012 to $11,153 in
      FY2015, P <= .001), and publications per faculty increased 15% (from 2.6 in
      FY2012 to 3.0 in FY2015, P < .001). Grant submissions, external funding, and
      teaching hours also increased per faculty but did not reach statistical
      significance. NEXT STEPS: An important next step will be to incorporate quality
      metrics into the compensation plan, without affecting costs or throughput.

PMID- 28746137
TI  - The Impact of an Academy of Medical Educators on the Culture of an American
      Health Sciences Campus.
AB  - PURPOSE: During the last two decades in the United States, academies of medical
      educators (AMEs) have proliferated as formal organizations within faculties of
      health professions education to recognize teaching excellence, support faculty
      development, and encourage scholarly activity. AMEs have been effective at
      rewarding faculty for educational excellence and providing faculty development.
      However, the impact of an AME on campus culture remains unclear. METHOD: A
      qualitative case study asked, How has an AME shaped organizational culture? The
      authors investigated the University of Colorado health sciences campus AME given
      its clear mandate to impact organizational culture. The authors interviewed a
      purposeful sample of 26 AME members and non-AME campus faculty and educational
      leaders during the 2014-2015 academic year. Two reviewers employed content
      analysis to code the transcripts. RESULTS: The AME has positively impacted
      organizational culture by being a symbol of institutional commitment to the
      educational mission, and by asserting education as an evidence-based practice. At
      the faculty member level, the AME's impact includes creating a home and community
      for educators to network. Individual faculty influence departments and programs
      across campus through teaching and interpersonal connections. However, the AME
      has not impacted all of campus, due to only reaching self-identified educators,
      and the siloed nature of departments on campus. CONCLUSIONS: Although limited to
      a single campus and an early established AME, this study contributes significant
      insight by describing how an AME as a structural unit impacts individual faculty
      members, who in turn impact organizational campus culture regarding the
      educational mission.

PMID- 28746138
TI  - Faculty-Resident "Co-learning": A Longitudinal Exploration of an Innovative Model
      for Faculty Development in Quality Improvement.
AB  - PURPOSE: To examine the effectiveness of co-learning, wherein faculty and
      trainees learn together, as a novel approach for building quality improvement
      (QI) faculty capacity. METHOD: From July 2012 through September 2015, the authors
      conducted 30 semistructured interviews with 23 faculty participants from the Co
      Learning QI Curriculum of the Department of Medicine, Faculty of Medicine,
      University of Toronto, and collected descriptive data on faculty participation
      and resident evaluations of teaching effectiveness. Interviewees were from 13
      subspecialty residency programs at their institution. RESULTS: Of the 56 faculty
      participants, the Co-Learning QI Curriculum trained 29 faculty mentors, 14 of
      whom taught formally. Faculty leads with an academic QI role, many of whom had
      prior QI training, reinforced their QI knowledge while also developing QI
      mentorship and teaching skills. Co-learning elements that contributed to QI
      teaching skills development included seeing first how the QI content is taught,
      learning through project mentorship, building experience longitudinally over
      time, a graded transition toward independent teaching, and a supportive program
      lead. Faculty with limited QI experience reported improved QI knowledge, skills,
      and project facilitation but were ambivalent about assuming a teacher role.
      Unplanned outcomes for both groups included QI teaching outside of the
      curriculum, applying QI principles to other work, networking, and strengthening
      one's QI professional role. CONCLUSIONS: The Co-Learning QI Curriculum was
      effective in improving faculty QI knowledge and skills and increased faculty
      capacity to teach and mentor QI. Findings suggest that a combination of
      curriculum and contextual factors were critical to realizing the curriculum's
      full potential.

PMID- 28746139
TI  - The Impact of a Scholarly Concentration Program on Student Interest in Career
      Long Research: A Longitudinal Study.
AB  - PURPOSE: Concerns remain regarding the future of the physician-scientist
      workforce. One goal of scholarly concentration (SC) programs is to give students
      skills and motivation to pursue research careers. The authors describe SC and
      student variables that affect students' career plans. METHOD: Medical students
      graduating from the University of Chicago SC program in 2014 and 2015 were
      studied. The authors measured change in interest in career-long research from
      matriculation to graduation, and used ordinal logistic regression to determine
      whether program satisfaction, dissemination of scholarship, publication, and
      gender were associated with increased interest in a research career. RESULTS:
      Among students with low baseline interest in career-long research, a one-point
      higher program satisfaction was associated with 2.49 (95% CI 1.36-4.57, P = .003)
      odds of a one-point-increased interest in a research career from matriculation to
      graduation. Among students with high baseline interest in career-long research,
      both publication (OR 5.46, 95% CI 1.40-21.32, P = .02) and female gender (OR
      4.83, 95% CI 1.11-21.04, P = .04) were associated with increased odds of a one
      point-increased interest in career-long research. CONCLUSIONS: The impact of an
      SC program on change in career plans during medical school was analyzed. Program
      satisfaction, publication, and female gender were associated with increased
      intent to participate in career-long research depending on baseline interest in
      career-long research. Two ways to bolster the physician-scientist workforce are
      to improve satisfaction with existing SC programs and to formally support student
      publication. Future work to track outcomes of SC program graduates is warranted.

PMID- 28746140
TI  - Are There 3D Changes in Spine and Rod Shape in the 2 Years After Adolescent
      Idiopathic Scoliosis Instrumentation?
AB  - STUDY DESIGN: Retrospective analysis of spine and rods 3D shape in the 2 years
      after adolescent idiopathic scoliosis (AIS) posterior surgical instrumentation.
      OBJECTIVE: To evaluate spine and rod shape 3D changes in the 2 years after AIS
      instrumentation with different rod materials. SUMMARY OF BACKGROUND DATA:
      Postoperative loss of correction has been reported with modern segmental
      instrumentation. The postoperative 3D rod shape changes of different rod
      materials and their implication in postoperative loss of correction have never
      been studied. METHODS: A total of 42 Lenke 1 AIS cases who underwent surgery all
      with pedicle screws and 5.5 mm rods of three different materials were
      retrospectively reviewed (14 cases for each of the three rod material subgroups:
      titanium, cobalt-chromium, stainless steel). 3D reconstructions of the spine were
      performed using biplanar radiographs preoperatively, 1-week postoperatively
      (1WPO), and 2 years follow-up (2YFU). Rods 3D shape also was reconstructed at
      1WPO and 2YFU. The spine and rods shapes were analyzed and compared between time
      points. RESULTS: An average of 1.93 implant per vertebra was used. The main
      thoracic curve (61 degrees  +/- 9 degrees ) was corrected on average by 75% (15
      degrees  +/- 6 degrees , P < 0.01) with no change at 2YFU (17 degrees  +/- 7
      degrees , P = 0.14). The apical vertebral rotation (23 degrees  +/- 7 degrees )
      was corrected by 44% (13 degrees  +/- 9 degrees , P < 0.01) with no change at
      2YFU (14 degrees  +/- 9 degrees , P = 0.64). The thoracic kyphosis (24 degrees 
      +/- 12 degrees ) remained unchanged (P = 0.78). The orientation of the planes of
      maximal curvature with respect to the sagittal plane of the main thoracic curve
      (39 degrees  +/- 15 degrees ) and of the rods (concave: 28 degrees  +/- 23
      degrees , convex: 12 degrees  +/- 10 degrees ) at 1WPO was unchanged at 2YFU (all
      P > 0.05). Rod curvature and deflection also remained unchanged (all P > 0.05).
      3D curve correction was maintained in the 2YFU for all rod materials subgroups
      (all P > 0.05). The lumbar lordosis changed from 1WPO (47 degrees  +/- 8 degrees
      ) to 2YFU (56 degrees  +/- 9 degrees , P < 0.01). At preoperatively, 57% of the
      cases had a balanced posture (sacral vertical axis/sacral femoral distance <=0.5
      and sacral vertical axis <=0), 33% at 1WPO and 79% at 2YFU. CONCLUSION: There was
      no significant 3D shape change of the instrumented thoracic spine or of the rods
      postoperatively for any of the segmental pedicle screw constructs with titanium,
      stainless steel, and cobalt-chromium rods. Patients overall unbalanced sagittal
      posture documented immediately after surgery came back to balanced 2 years after
      surgery. LEVEL OF EVIDENCE: 3.

PMID- 28746141
TI  - Advancing Individualized Developmental Care: Context and Substance.

PMID- 28746143
TI  - Supporting Nurses as Lifelong Learners.

PMID- 28746144
TI  - Effects of Cycled Lighting Versus Continuous Near Darkness on Physiological
      Stability and Motor Activity Level in Preterm Infants.

PMID- 28746145
TI  - Treatment and outcomes of type 2 myocardial infarction and myocardial injury
      compared with type 1 myocardial infarction.
AB  - BACKGROUND: Type 2 myocardial infarction (MI) is defined by a rise and fall of
      cardiac biomarkers and evidence of ischemia without unstable coronary artery
      disease (CAD) because of a mismatch in myocardial oxygen supply and demand.
      Myocardial injury is similar but does not fulfill the clinical criteria for MI.
      There is uncertainty in terms of the clinical characteristics, management, and
      outcomes of type 2 MI and myocardial injury in comparison with type 1 MI.
      PATIENTS AND METHODS: Patients admitted to a Veterans Affairs tertiary care
      hospital with a rise and fall in cardiac troponin were identified. MI and injury
      subtypes, presentation, management, and outcomes were determined. RESULTS: Type 1
      MI, type 2 MI, and myocardial injury occurred in 137, 146, and 175 patients,
      respectively. Patients with type 2 MI were older (P=0.02), had lower peak cardiac
      troponin (P<0.001), and were less likely to receive aspirin and statin at
      discharge (P<0.001) than type 1 MI survivors. All-cause mortality (median follow
      up: 1.8 years) was not different between patient groups (type 1 MI mortality:
      29.9%, type 2 MI: 30.8%, myocardial injury: 29.7%; log rank P=0.94). A
      significant proportion of deaths were attributed to cardiovascular causes in all
      subgroups (type 1 MI: 34.1%, type 2 MI: 17.8%, myocardial injury: 30.8%).
      CONCLUSION: Patients with type 2 MI and myocardial injury were less likely to
      receive medical therapy for CAD than those with type 1 MI. No differences in all
      cause mortality among MI subtypes were observed. Additional studies to determine
      optimal medical therapy and risk stratification strategies for these high-risk
      populations are warranted.

PMID- 28746146
TI  - Isolated native tricuspid valve endocarditis due to group A beta-hemolytic
      Streptococcus without drug addiction.

PMID- 28746147
TI  - Aneurysm of Vieussens' arterial ring in a patient studied with coronary computed
      tomography.

PMID- 28746148
TI  - An accordion not to be played.

PMID- 28746149
TI  - Multimodality cardiac imaging of infective endocarditis.

PMID- 28746150
TI  - Refractory idiopathic recurrent pericarditis: treatment with interleukin-1
      receptor antagonist is an option!

PMID- 28746151
TI  - Bilateral Upper Lobe Bronchi Originating from the Trachea.

PMID- 28746152
TI  - Intraoperative Molecular Imaging Combined With Positron Emission Tomography
      Improves Surgical Management of Peripheral Malignant Pulmonary Nodules.
AB  - OBJECTIVE: To determine if intraoperative molecular imaging (IMI) can improve
      detection of malignant pulmonary nodules. BACKGROUND: 18-Fluorodeoxyglucose
      positron emission tomography (PET) is commonly utilized in preoperative
      assessment of patients with solid malignancies; however, false negatives and
      false positives remain major limitations. Using patients with pulmonary nodules
      as a study model, we hypothesized that IMI with a folate receptor targeted near
      infrared contrast agent (OTL38) can improve malignant pulmonary nodule
      identification when combined with PET. METHODS: Fifty patients with pulmonary
      nodules with imaging features suspicious for malignancy underwent preoperative
      PET. Patients then received OTL38 before pulmonary resection. During resection,
      IMI was utilized to evaluate known pulmonary nodules and identify synchronous
      lesions. Tumor size, PET standardized uptake value, and IMI tumor-to-background
      ratios were compared for known and synchronous nodules via paired and unpaired t
      tests, when appropriate. Test characteristics of PET and IMI with OTL38 were
      compared. RESULTS: IMI identified 56 of 59 (94.9%) malignant pulmonary nodules
      identified by preoperative imaging. IMI located an additional 9 malignant lesions
      not identified preoperatively. Nodules only detected by IMI were smaller than
      nodules detected preoperatively (0.5 vs 2.4 cm; P < 0.01), but displayed similar
      fluorescence (tumor-to-background ratio 3.3 and 3.1; P = 0.50). Sensitivity of
      IMI and PET were 95.6% and 73.5% (P = 0.001), respectively; and positive
      predictive values were 94.2% and 89.3%, respectively (P > 0.05). Additionally,
      utilization of IMI clinically upstaged 6 (12%) subjects and improved management
      of 15 (30%) subjects. CONCLUSIONS: These data suggest that combining IMI with PET
      may provide superior oncologic outcomes for patients with resectable lung cancer.

PMID- 28746153
TI  - A Randomized Controlled Trial of Postoperative Thoracic Epidural Analgesia Versus
      Intravenous Patient-controlled Analgesia After Major Hepatopancreatobiliary
      Surgery.
AB  - OBJECTIVES: The primary objective of this randomized trial was to compare
      thoracic epidural analgesia (TEA) to intravenous patient-controlled analgesia (IV
      PCA) for pain control over the first 48 hours after hepatopancreatobiliary (HPB)
      surgery. Secondary endpoints were patient-reported outcomes, total narcotic
      utilization, and complications. BACKGROUND: Although adequate postoperative pain
      control is critical to patient and surgeon success, the optimal analgesia regimen
      in HPB surgery remains controversial. METHODS: Using a 2.5:1 randomization
      strategy, 140 patients were randomized to TEA (N = 106) or intravenous patient
      controlled analgesia (N = 34). Patient-reported pain was measured on a Likert
      scale (0-10) at standard time intervals. Cumulative pain area under the curve was
      determined using the trapezoidal method. RESULTS: Between the study groups key
      demographic, comorbidity, clinical, and operative variables were equivalently
      distributed. The median area under the curve of the postoperative time 0- to 48
      hour pain scores was lower in the TEA group (78.6 vs 105.2 pain-hours, P = 0.032)
      with a 35% reduction in patients experiencing >=7/10 pain (43% vs 62%, P = 0.07).
      Patient-reported outcomes and total opiate use further supported the benefit of
      TEA on patient experience. Anesthesia-related events requiring change in
      analgesic therapy were comparable (12.2% vs 2.9%, respectively, P = 0.187). Grade
      3 or higher surgical complications (6.6% vs 9.4%), median length of stay (6 days
      vs 6 days), readmission (1.9% vs 3.1%), and return to the operating room (0.9% vs
      3.1%) were similar (all P > 0.05). There were no mortalities in either group.
      CONCLUSIONS: In major HPB surgery, TEA provides a superior patient experience
      through improved pain control and less narcotic use, without increased length of
      stay or complications.

PMID- 28746155
TI  - Evaluation of New Classifications for Liver Surgery: Can Anatomic Granularity
      Predict Both Complexity and Outcomes of Hepatic Resection?

PMID- 28746157
TI  - Laparoscopic Hepatectomy for Hepatocellular Carcinoma: The Opportunities, the
      Challenges, and the Limitations.

PMID- 28746156
TI  - Textbook Outcome: A Composite Measure for Quality of Elective Aneurysm Surgery.
AB  - OBJECTIVE: To investigate a new composite quality measurement, which comprises a
      desirable outcome for elective aneurysm surgery, called "Textbook Outcome" (TO).
      BACKGROUND: Single-quality indicators in vascular surgery are often not
      distinctive and insufficiently reflect the quality of care. METHODS: All patients
      undergoing elective abdominal aortic aneurysm repair, registered in the Dutch
      Surgical Aneurysm Audit between 2014 and 2015 were included. TO was defined as
      the percentage of patients who had abdominal aortic aneurysm-repair without
      intraoperative complications, postoperative surgical complications,
      reinterventions, prolonged hospital stay [endovascular aneurysm repair (EVAR) <=4
      d, open surgical repair (OSR) <=10 d], readmissions, and postoperative mortality
      (<=30 d after surgery/at discharge). Case-mix adjusted TO rates were used to
      compare hospitals and to compare individual hospital results for different
      procedures. RESULTS: Five thousand one hundred seventy patients were included, of
      whom 4039 were treated with EVAR and 1131 with OSR. TO was achieved in 71% of
      EVAR and 53% of OSR. Important obstacles for achieving TO were a prolonged
      hospital stay, postoperative complications, and readmissions. Adjusted TO rates
      varied from 38% to 89% (EVAR) and from 0% to 97% (OSR) between individual
      hospitals. Hospitals with a high TO for OSR also had a high TO for EVAR; however,
      a high TO for EVAR did not implicate a high TO for OSR. CONCLUSIONS: TO generates
      additional information to evaluate the overall quality of the care of elective
      aneurysm surgery, which subsequently can be used by hospitals to improve the
      quality of their care.

PMID- 28746154
TI  - Anastomotic Leakage and Chronic Presacral Sinus Formation After Low Anterior
      Resection: Results From a Large Cross-sectional Study.
AB  - OBJECTIVES: Little is known about late detected anastomotic leakage after low
      anterior resection for rectal cancer, and the proportion of leakages that
      develops into a chronic presacral sinus. METHODS: In this collaborative snapshot
      research project, data from registered rectal cancer resections in the Dutch
      Surgical Colorectal Audit in 2011 were extended with additional treatment and
      long-term outcome data. Independent predictors for anastomotic leakage were
      determined using a binary logistic model. RESULTS: A total of 71 out of the
      potential 94 hospitals participated. From the 2095 registered patients, 998
      underwent a low anterior resection, of whom 88.8% received any form of
      neoadjuvant therapy. Median follow-up was 43 months (interquartile range 35-47).
      Anastomotic leakage was diagnosed in 13.4% within 30 days, which increased to
      20.0% (200/998) beyond 30 days. Nonhealing of the leakage at 12 months was 48%,
      resulting in an overall proportion of chronic presacral sinus of 9.5%.
      Independent predictors for anastomotic leakage at any time during follow-up were
      neoadjuvant therapy (odds ratio 2.85; 95% confidence interval 1.00-8.11) and a
      distal (<=3 cm from the anorectal junction on magnetic resonance imaging) tumor
      location (odds ratio 1.88; 95% confidence interval 1.02-3.46). CONCLUSIONS: This
      cross-sectional study of low anterior resection for rectal cancer in the
      Netherlands in 2011, with almost routine use of neoadjuvant radiotherapy, shows
      that one third of anastomotic leakages is diagnosed beyond 30 days, and almost
      half of the leakages eventually do not heal. Chronic presacral sinus is a
      significant clinical problem that deserves more attention.

PMID- 28746158
TI  - Lactate serum concentrations during treatment with nucleos(t)ide analogues in
      hepatitis B with or without cirrhosis.
AB  - OBJECTIVE: The aim of this study is to evaluate the clinical implications of
      lactate concentrations in patients with hepatitis B with or without cirrhosis
      during treatment with nucleos(t)ide analogues. PATIENTS AND METHODS: One hundred
      and seven consecutive patients with chronic hepatitis B and median age 57 (24-85)
      years were prospectively included. Lactate concentrations were measured at
      baseline and at 12, 24, 36, 48, and 60 months following the baseline
      measurements. Eight (n=8, 7.5%) patients received lamivudine, 38 (n=38, 35.5%)
      patients received tenofovir, 34 (n=34, 31.8%) patients received entecavir, and 27
      (n=27, 25.2%) patients received combined therapy. RESULTS: None of the patients
      developed lactic acidosis during follow-up [median: 58 (6-155) months]. Overall,
      no trends of the lactic acid evolution were observed over time; however, there
      was a nonsignificant increasing trend in patients with cirrhosis up to 24 months
      of treatment. This increasing trend was significant in female patients with
      cirrhosis (P=0.016). The age of the patients, the presence of cirrhosis, and
      hepatocellular carcinoma were strongly associated with the survival of all
      patients. In the group of cirrhotic patients, the only independent prognostic
      factor that was associated with patients' survival was the Child-Pugh class.
      CONCLUSION: None of the patients developed lactic acidosis. There is an
      indication of an increasing trend of lactic acid levels up to 24 months of
      therapy in female cirrhotic patients.

PMID- 28746159
TI  - Percutaneous endoscopic gastrostomy: confirming the clinical benefits far beyond
      anthropometry.
AB  - OBJECTIVES: The real benefit of gastrostomy is still a matter of debate. We aimed
      to prospectively evaluate the global impact of percutaneous endoscopic
      gastrostomy (PEG) in patients followed at a specialized multidisciplinary clinic,
      namely, the impact on the need for healthcare resources, anthropometric measures,
      pressure ulcers prevention and healing, and nutritional and hydration status.
      PATIENTS AND METHODS: From the 201 patients who underwent PEG between May 2011
      and September 2014, 60 were included in a prospective study. Anthropometric,
      clinical, and laboratorial variables were collected and compared before and after
      PEG. Follow-up duration, mortality, and number of emergency department visits or
      hospital admissions were also assessed. RESULTS: Thirty-three (55.0%) patients
      were women and the median age was 79 years. The main indications for PEG were
      dementia (43.3%) and poststroke dysphagia (30.0%). Four months following PEG,
      significant decreases in the tricipital skinfold (P=0.002) and brachial perimeter
      (P=0.003) were found. A decrease in the mean number of hospitalizations (1.4 vs.
      0.3; P<0.001) and visits to emergency department (2.2 vs. 1.1; P=0.003) was noted
      in the next 6 months after PEG compared with the previous semester. In 53.8% of
      patients with pressure ulcers, complete healing was observed after PEG. PEG was
      associated with increases in hemoglobin (P=0.024), lymphocytes (P=0.041),
      cholesterol (P=0.008), transferrin (P<0.001), albumin (P<0.001), and total
      proteins (P<0.001), and a decrease in serum sodium (P=0.001). CONCLUSION:
      Anthropometric values may not translate the early benefits of a gastrostomy. PEG
      decreases the need for hospital health care, facilitates healing of pressure
      ulcers, and induces biochemical changes that may reflect better nutrition and
      hydration.

PMID- 28746160
TI  - The impact of genetic polymorphisms on liver diseases: entering the era of
      personalized medicine.

PMID- 28746162
TI  - Lung cancer and annual mean exposure to outdoor air pollution in Crete, Greece.
AB  - The increasing burden of lung cancer (LC) in Crete, Greece, has raised certain
      concerns about the potential association of environmental risk factors with LC.
      The aim of this study was to assess outdoor air pollution (OAP) and the risk for
      LC mortality for the first time in Crete using LC primary data. 5057 LC cases
      (diagnosed from 1992 to 2013) were obtained from the Cancer Registry of Crete
      (http://www.crc.uoc.gr) and followed up until 2014. The age-standardized
      incidence and mortality rates (ASIR) were calculated. Data on OAP indicators
      [particulate matter (PM)2.5, between 2.5 and 10 MUm (PM2.5-10), PM10, PM2.5
      absorbance (black carbon measure), nitrogen dioxide (NO2), and nitrogen oxides
      (NOx)] were collected. Spatial statistics were calculated and the binary logistic
      regression model was constructed at alpha=0.05 in IBM SPSS 24 and ArcMap 10.3.1.
      LC in Crete accounts for 40.2 new cases/100 000/year for both sexes
      (ASIRmales=73.1 new cases/100 000/year; ASIRfemales=11.8 new cases/100 000/year).
      Annual median estimates of environmental concentrations in Crete were as follows:
      PM2.5=20.7 (+/-1.5) ug/m, PM10=38.9 (+/-2.5) ug/m, PM2.5-10=59.6 (+/-3.7) ug/m,
      PM2.5 absorbance=1.2 (+/-0.3)*10/m, NO2=15.2 (+/-3.8) ug/m, and NOx=20.1 (+/-4.9)
      ug/m. A statistically significant association was observed between OAP and LC
      mortality (mean correlation coefficient=0.75; P<0.05). The highest risk for 5
      year LC mortality was found in the major urban centers and several south-east and
      north-west rural regions of Crete (relative risk=3.2, 95% confidence interval=1.6
      4.7). OAP seems to be an important determinant of LC mortality. Targeted
      interventions should be performed in the high-risk areas.

PMID- 28746163
TI  - The potential contribution of dietary factors to breast cancer prevention.
AB  - Breast cancer (BC), the leading cancer in women, is increasing in prevalence
      worldwide, concurrent with western metabolic epidemics, that is, obesity,
      metabolic syndrome, and diabetes, and shares major risk factors with these
      diseases. The corresponding potential for nutritional contributions toward BC
      prevention is reviewed and related to critical stages in the life cycle and their
      implications for carcinogenic and pathometabolic trajectories. BC initiation
      potentially involves diet-related pro-oxidative, inflammatory, and
      procarcinogenic processes, that interact through combined lipid/fatty acid
      peroxidation, estrogen metabolism, and related DNA-adduct/depurination/mutation
      formation. The pathometabolic trajectory is affected by high estrogen, insulin,
      and growth factor cascades and resultant accelerated proliferation/progression.
      Anthropometric risk factors - high birth weight, adult tallness, adiposity/BMI,
      and weight gain - are often reflective of these trends. A sex-based nutritional
      approach targets women's specific risk in western obesogenic environments,
      associated with increasing fatness, estrogen metabolism, n-6 : n-3
      polyunsaturated fatty acid ratio, and n-6 polyunsaturated fatty acid conversion
      to proinflammatory/carcinogenic eicosanoids, and effects of timing of life
      events, for example, ages at menarche, full-term pregnancy, and menopause. Recent
      large-scale studies have confirmed the effectiveness of the evidence-based
      recommendations against BC risk, emphasizing low-energy density diets, highly
      nutritious plant-based regimes, physical activity, and body/abdominal adiposity
      management. Better understanding of dietary inter-relationships with BC, as
      applied to food intake, selection, combination, and processing/preparation, and
      recommended patterns, for example, Mediterranean, DASH, plant-based, low energy
      density, and low glycemic load, with high nutrient/phytonutrient density, would
      increase public motivation and authoritative support for early/timely prevention,
      optimally merging with other dietary/health goals, for lifelong BC prevention.

PMID- 28746164
TI  - Implementation of a Novel Adherence Monitoring Strategy in a Phase III, Blinded,
      Placebo-Controlled, HIV-1 Prevention Clinical Trial.
AB  - BACKGROUND: Placebo-controlled HIV-1 prevention trials of pre-exposure
      prophylaxis (PrEP) have not generally used concurrent measurement of adherence
      because of the potential risk of unblinding. However, several pre-exposure
      prophylaxis trials for HIV-1 prevention among women failed to show effectiveness
      because of low product adherence. Evaluation of product adherence objectively
      during a study provides the opportunity for strengthening adherence activities at
      sites having low adherence. METHODS: During MTN-020/ASPIRE, a phase III, placebo
      controlled trial of the dapivirine intravaginal ring, we implemented an adherence
      monitoring system. Monitoring began in quarter 1 (Q1) 2013 and continued through
      the conclusion of the trial. Blood plasma was collected quarterly and tested for
      dapivirine concentrations while maintaining blinding among study team members
      involved in participant management. Dapivirine concentrations >95 pg/mL,
      reflecting >8 hours of continuous use, were assessed as signaling product use.
      Study leadership monitored results on a monthly basis and provided feedback to
      site investigators. Experiences were shared across sites to motivate staff and
      counsel participants to strive toward higher adherence levels. RESULTS: An upward
      trend in adherence was observed (P < 0.0001); the proportion of samples from
      subjects in the active arm with dapivirine >95 pg/mL increased from 63% in Q1
      2013 to 84% by Q1 2015. CONCLUSIONS: Ongoing drug level testing as a marker of
      adherence in MTN-020/ASPIRE demonstrates the feasibility of real-time adherence
      monitoring while maintaining study blinding at the level of participants, sites,
      and study leadership. This approach is novel for large-scale effectiveness
      studies for HIV-1 prevention.

PMID- 28746165
TI  - Effect of Immediate Initiation of Antiretroviral Treatment in HIV-Positive
      Individuals Aged 50 Years or Older.
AB  - BACKGROUND: Clinical guidelines recommend immediate initiation of combined
      antiretroviral therapy for all HIV-positive individuals. However, those
      guidelines are based on trials of relatively young participants. METHODS: We
      included HIV-positive antiretroviral therapy-naive, AIDS-free individuals aged 50
      70 years after 2004 in the HIV-CAUSAL Collaboration. We used the parametric g
      formula to estimate the 5-year risk of all-cause and non-AIDS mortality under (1)
      immediate initiation at baseline and initiation at CD4 count, (2) <500 cells/mm,
      and (3) <350 cells/mm. Results were presented separately for the general HIV
      population and for a US Veterans cohort with high mortality. RESULTS: The study
      included 9596 individuals (28% US Veterans) with median (interquantile range) age
      of 55 (52-60) years and CD4 count of 336 (182-513) at baseline. The 5-year risk
      of all-cause mortality was 0.40% (95% confidence interval (CI): 0.10 to 0.71)
      lower for the general HIV population and 1.61% (95% CI: 0.79 to 2.67) lower for
      US Veterans when comparing immediate initiation vs initiation at CD4 <350
      cells/mm. The 5-year risk of non-AIDS mortality was 0.17% (95% CI: -0.07 to 0.43)
      lower for the general HIV population and 1% (95% CI: 0.31 to 2.00) lower for US
      Veterans when comparing immediate initiation vs initiation at CD4 <350 cells/mm.
      CONCLUSIONS: Immediate initiation seems to reduce all-cause and non-AIDS
      mortality in patients aged 50-70 years.

PMID- 28746166
TI  - The Association Between Intimate Partner Violence and Women's Distribution and
      Use of HIV Self-Tests With Male Partners: Evidence From a Cohort Study in Kenya.

PMID- 28746167
TI  - Factors Associated With Prevalent HIV Infection Among Kenyan MSM: The Anza Mapema
      Study.
AB  - BACKGROUND: To inform future HIV treatment and care programs for men who have sex
      with men (MSM), we assessed the prevalence of and factors associated with
      previously diagnosed HIV-positive and out-of-care (PDOC) or newly diagnosed HIV
      positive and out-of-care (NDOC) HIV infection among MSM enrolled in the
      prospective Anza Mapema cohort study. METHODS: Participants were aged 18 years
      and older, reported oral or anal sex with a man in the past 6 months and were not
      already in HIV care or taking antiretroviral therapy in the past 3 months. At
      enrollment, men were tested for HIV infection and completed questionnaires
      through audio computer-assisted self-interview. Multinomial logistic regression
      was used to identify associations with PDOC or NDOC HIV infection, relative to
      HIV-negative status. RESULTS: Among 711 enrolled men, 75 (10.5%) were
      seropositive including 21 PDOC and 54 NDOC men. In multivariable modeling, PDOC
      status was more likely than HIV-negative status among men who had experienced
      upsetting sexual experiences during childhood, had recently experienced MSM
      trauma, and did not report harmful alcohol use. NDOC infection status was more
      common among men aged 30 years and older and who had completed <=8 years of
      education, relative to HIV-negative status. CONCLUSIONS: Most HIV-positive men
      were unaware of their infection, indicating that HIV testing and counseling
      services tailored to this population are needed. To improve linkage to and
      retention in care, HIV testing and care services for MSM should screen and
      provide support for those with hazardous alcohol use and those who have
      experienced childhood sexual abuse or MSM trauma.

PMID- 28746168
TI  - HIV Self-Testing in Italy.

PMID- 28746169
TI  - Traditional Long-Term Central Venous Catheters Versus Transhepatic Venous
      Catheters in Infants and Young Children.
AB  - OBJECTIVES: Children with congenital heart disease may require long-term central
      venous access for intensive care management; however, central venous access must
      also be preserved for future surgical and catheterization procedures.
      Transhepatic venous catheters may be an useful alternative. The objective of this
      study was to compare transhepatic venous catheters with traditional central
      venous catheters regarding complication rate and duration of catheter service.
      DESIGN: Retrospective review of 12 congenital heart disease patients from
      September 2013 to July 2015 who underwent placement of one or more transhepatic
      venous catheters. SETTING: Single freestanding pediatric hospital located in the
      central United States. PATIENTS: Pediatric patients with congenital heart disease
      who underwent placement of transhepatic venous catheter. INTERVENTIONS: Cohort's
      central venous catheter complication rates and duration of catheter service were
      compared with transhepatic venous catheter data. MEASUREMENTS AND MAIN RESULTS:
      Twelve patients had a total of 19 transhepatic venous lines. Transhepatic venous
      lines had a significantly longer duration of service than central venous lines (p
      = 0.001). No difference between the two groups was found in the number of
      documented thrombi, thrombolytic burden, or catheter sites requiring wound care
      consultation. A higher frequency of infection in transhepatic venous lines versus
      central venous lines was found, isolated to four transhepatic venous lines that
      had a total of nine infections. All but one was successfully managed without
      catheter removal. The difference in the proportion of infections to catheters in
      transhepatic venous lines versus central venous lines was significant (p =
      0.0001), but no difference in the rate of infection-related catheter removal was
      found. CONCLUSIONS: Without compromising future central venous access sites,
      transhepatic venous lines had superior duration of service without increased
      thrombosis, thrombolytic use, or insertion site complications relative to central
      venous lines. Transhepatic venous catheters had a higher infection rate, and
      further investigation into the etiology is warranted.

PMID- 28746170
TI  - Multiple ectopic hepatocellular carcinomas in the pancreas: A case report.
AB  - RATIONALE: Ectopic liver tissue can develop at various sites near the liver.
      Ectopic hepatocellular carcinomas (HCCs) arising from ectopic liver tissue have a
      rare clinical incidence. A very rare case has been observed to have metastasis
      after operation. PATIENT CONCERNS: We report an extremely rare case with multiple
      masses which were identified in the head and body of the pancreas. DIAGNOSES:
      Ectopic hepatocellular carcinomas. INTERVENTIONS: The masses were removed by
      surgical resection. Histopathological analysis showed that both masses were
      ectopic HCC. OUTCOMES: The patient was still alive and did not have metastasis
      and relapse. LESSONS: The literature review for this rare case is also presented
      to highlight the risk of ectopic HCC and good prognosis of operation for ectopic
      HCC.

PMID- 28746171
TI  - The value of APACHE II in predicting mortality after paraquat poisoning in
      Chinese and Korean population: A systematic review and meta-analysis.
AB  - BACKGROUND: The Acute Physiology and Chronic Health Evaluation II (APACHE II)
      score is used to determine disease severity and predict outcomes in critically
      ill patients. However, the prognostic significance of APACHE after acute paraquat
      (PQ) poisoning remains unclear. The meta-analysis was aimed to study the value of
      APACHE II in predicting mortality in PQ-exposed Chinese and Korean patients.
      METHODS: Databases that included PubMed, Embase, Cochrane Library, and the
      Chinese National Knowledge Infrastructure were searched through August 2016.
      Studies using APACHE II to predict mortality in PQ-poisoned patients were
      selected. The odds ratio and weighted mean difference (WMD) were used to pool
      binary and continuous data. Additionally, we aggregated sensitivity, specificity,
      and other measures of accuracy. Statistical analyses were made using the Stata
      V.13.0 software. RESULTS: This study included 29 studies, and 25 studies
      evaluated APACHE II scores on admission. Pooled data showed that survivors had
      significantly lower total scores than nonsurvivors (WMD = -7.29, and I = 98.2%,
      both P <.05). The pooled sensitivity of an APACHE II score >=5 for predicting
      mortality was 75% and the pooled specificity was 86%. The positive likelihood
      ratio (PLR) was 5.3 and the negative likelihood ratio (NLR) was 0.29. The pooled
      sensitivity of an APACHE II score >=10 for predicting mortality was 88% and the
      pooled specificity was 84%. The pooled PLR and NLR was 5.5 and 0.15,
      respectively. CONCLUSION: This study showed PQ-poisoned nonsurvivors had
      significantly higher APACHE II score than did survivors. APACHE II scores
      satisfactorily predicted mortality.

PMID- 28746172
TI  - A genetic variant in the catechol-O-methyl transferase (COMT) gene is related to
      age-dependent differences in the therapeutic effect of calcium-channel blockers.
AB  - Hypertension is the leading risk factor for cardiovascular disease and one of the
      major health concerns worldwide. Genetic factors impact both the risk for
      hypertension and the therapeutic effect of antihypertensive drugs. Sex- and age
      specific variances in the prevalence of hypertension are partly induced by
      estrogen. We investigated 6 single nucleotide polymorphisms in genes encoding
      enzymes involved in estrogen metabolism in relation to sex- and age-specific
      differences in the systolic and diastolic blood pressure (SBP and DBP) outcome
      under the treatment of diuretics, calcium-channel blockers (CCBs), angiotensin
      converting-enzyme inhibitors, and angiotensin-receptor blockers (ARBs).We
      included 5064 subjects (age: 40-82) from the population-based CoLaus cohort.
      Participants were genotyped for the catechol-O-methyltransferase gene (COMT)
      variants rs4680, rs737865, and rs165599; the uridine-diphospho
      glucuronosyltransferase 1A gene family (UGT1A) variants rs2070959 and rs887829;
      and the aromatase gene (CYP19A1) variant rs10046. Binomial and linear regression
      analyses were performed correcting for age, sex, body mass index, smoking,
      diabetes, and antihypertensive therapy to test whether the variants in focus are
      significantly associated with BP.All investigated COMT variants were strongly
      associated with the effect of diuretics, CCBs, and ARBs on SBP or DBP (P < .05),
      showing an additive effect when occurring in combination. After Bonferroni
      correction the polymorphism rs4680 (ValMet) in COMT was significantly associated
      with lower SBP in participants treated with CCBs (P = .009) with an especially
      strong impact in elderly individuals (age >= 70) alone (Delta = -14.08 mm Hg, P =
      .0005).These results underline the important role of estrogens and catecholamines
      in hypertension and the importance of genotype dependent, age-related adjustments
      of calcium-channel blocker treatment.

PMID- 28746173
TI  - Ultrasonographic diagnosis and minimally invasive treatment of a patent urachus
      associated with a patent omphalomesenteric duct in a newborn: A case report.
AB  - RATIONAL: Patent urachus (PU) is due to an incomplete obliteration of the
      urachus, whereas patent omphalomesenteric duct (POMD) is due to an incomplete
      obliteration of the vitelline duct. These anomalies are very rarely associated
      with one another. We describe a case of a newborn with a PU associated with a
      POMD, who was diagnosed by an abdominal ultrasound (US) and laparoscopy, and
      managed with a minimally invasive excision. PATIENT CONCERN: A 28-day-old male
      neonate was referred to our hospital to investigate a delay in umbilical healing,
      with blood-mucinous material spillage for 3 weeks prior to the referral. The baby
      had no symptoms and was in good general health. DIAGNOSIS: After a thorough
      cleaning of the umbilical stump, a clear granuloma with a suspected fistula was
      evident under the seat of the ligature of the stump. An abdominal US examination
      revealed the formation of a full communication, starting below the umbilical
      stump and developing along the anterior abdominal wall that connected with the
      bladder dome. The US also revealed a tubular formation containing air, which was
      compatible with POMD, in the deepest portion of the same umbilical stump.
      Considering these findings, the rare diagnosis of a PU associated with a POMD
      duct was suspected. INTERVENTIONS: The child was then hospitalized for an
      elective laparoscopy that confirmed the US picture, and a minimally invasive
      excision was performed. OUTCOME: The postoperative course was favorable and
      uneventful. LESSONS: Our case underlines the importance of evaluating all
      persisting umbilical lesions without delay when conventional pharmacological
      therapies fail. Using a US as the first approach is valuable and should be
      supported by laparoscopy to confirm the diagnosis; a minimally invasive excision
      of the remnants appears to be an effective therapeutic approach.

PMID- 28746174
TI  - Traumatic cataract in patient with anterior megalophthalmos: Case report.
AB  - RATIONALE: Megalophthalmos anterior is a rare, bilateral, nonprogressive,
      hereditary, congenital disorder, characterized by the enlargement of all anterior
      segment structures of the eye, with megalocornea, iris atrophy, and zonular
      abnormalities commonly found. Usually almost asymptomatic in young patients, with
      most complaints concerning blurred vision due to the common corneal astigmatism,
      it might in time lead to several complications including premature cataract
      formation and pigmentary glaucoma. PATIENT CONCERNS: This review presents the
      case of a 47-year old patient referred to our clinic for traumatic cataract
      surgery, with striking bilateral megalocornea, somehow overlooked during previous
      ophthalmic examinations in his local outpatient clinic. DIAGNOSIS: We noticed
      markedly enlarged corneas and deepened anterior chambers of his both eyes,
      accompanied by intumescent, white cataract of the right eye, and incipient
      cortical cataract of the left eye. Best corrected visual acuity (BCVA) was
      counting fingers in the right eye and 20/25 in the left eye. Additional
      examination revealed multiple abnormalities of the anterior segment, leading to
      the diagnosis of anterior megalophthalmos. It is astounding the patient remained
      undiagnosed during previous examinations, with his megalocornea and remarkably
      deep anterior chamber so apparent. INTERVENTIONS AND OUTCOMES: We performed
      standard phacoemulsification procedure, with 3 piece posterior chamber
      intraocular lens (PCIOL) implantation into the lens capsule. The surgery was
      uneventful, with postoperative BCVA of 20/20 in the right eye, and no dislocation
      of the lens in 9-month observation period. LESSONS: Complicated cataract in
      patients with anterior megalophthalmos can be successfully treated with standard
      phacoemulsification procedure followed by the bag PCIOL implantation.Care needs
      to be taken during cataract surgery in these patients, as zonular abnormalities
      and lens enlargement are common, resulting in increased rate of intra- and
      postoperative complications. As patients with anterior megalophthalmos require a
      more careful follow-up.

PMID- 28746175
TI  - A phase II clinical study of combining FOLFIRI and bevacizumab plus erlotinib in
      2nd-line chemotherapy for patients with metastatic colorectal cancer.
AB  - We conducted an open-label single-arm phase II study by combining irinotecan
      (FOLFIRI) and bevacizumab (BV) plus erlotinib (ER) in 2nd-line chemotherapy for
      patients with metastatic colorectal cancer (mCRC).Eligible mCRC patients received
      1st-line standard chemotherapy but still had progressive disease. They were given
      FOLFIRI plus BV at 2.5 mg/kg on day 1 per 2-week cycle, and daily 150 mg ER. The
      primary endpoint is progression-free survival (PFS).A total of 122 patients
      enrolled in the study. Among them, 55.7% were male patients and median age was
      58.4 years (29-72 years). Median PFS was 7.1 months (95% CI 4.3-10.2). Median
      overall survival (OS) was 13.5 months (95% CI 9.7-16.4). No patients had complete
      responses, 24 patients had partial response (19.6%) and 59 had stable disease
      (48.4%). The most frequent adverse event (AE) was rash, with 66 patients (54.1%)
      had grade 3/4 rash. Other frequent grade 3/4 AEs were fatigue (n = 36, 29.5%),
      bleeding (n = 31, 25.4%), neutropenia (n = 23, 18.9%), and platelets (n = 14,
      11.5%).Combining FOLFIRI and BV plus ER in 2nd-line chemotherapy is efficient to
      treat mCRC patients with acceptable safety.

PMID- 28746176
TI  - Comparison of clinical outcomes after endoscopic submucosal dissection and
      surgery in the treatment of early gastric cancer: A single-institute study.
AB  - The feasibility of expanding the indications for endoscopic submucosal dissection
      to treat early gastric cancer based on long-term outcomes has shown conflicting
      results. This study aimed to investigate whether outcomes or adverse events
      associated with endoscopic submucosal dissection are comparable to those of
      surgery for early gastric cancer that including the absolute and expanded
      indications.Data of 159 early gastric cancers from 153 patients treated with
      endoscopic submucosal dissection or surgery between January 2004 and October 2014
      were reviewed retrospectively. Early gastric cancers fulfilled the absolute or
      expanded indications with differentiated type adenocarcinoma were included.The
      endoscopic submucosal dissection and surgery group showed no significant
      difference in the incidence of residual disease (P = .48), local recurrence (P =
      .46), and metachronous cancer (P = .22). Kaplan-Meier analysis showed no
      significant difference in 2-year (97.6% versus [vs] 92.4%; P = .45) and 5-year
      (95.8% vs 95.6%; P = .26) overall survival rate between 2 groups. There was also
      no significant difference in 2-year (100% vs 94.1%; P = .98) and 5-year (100% vs
      98.4%; P = .89) disease-free survival rate. Early and late adverse events also
      showed no significant differences.For the treatment of early gastric cancer
      fulfilled absolute and expanded indications, endoscopic submucosal dissection is
      not inferior modality regarding the clinical outcomes and safety, compared with
      surgery.

PMID- 28746177
TI  - Correlation between high-intensity zone on MRI and discography in patients with
      low back pain.
AB  - The aim of this study was to analyze the correlation between high-intensity zone
      (HIZ) on magnetic resonance imaging (MRI) of a lumbar disc and positive pain
      response assessed by discography for the diagnosis and treatment of discogenic
      low back pain (LBP). Thirty-seven patients aged 21 to 59 years with chronic LBP
      but without any neurological symptoms or lumbar disc herniation who underwent MRI
      and subsequent discography were included in this study. During discography,
      concordant pain was regarded as positive, whereas discordant pain and no pain
      were regarded as negative. X-ray and computed tomography (CT) after discography
      with positive pain response were analyzed to correlate with HIZ on MRI. A total
      of 98 discs underwent discography in 37 patients; 21 discs presented positive
      pain response, including 10 with HIZ (47.6%). Seventy-seven discs presented
      negative pain response, including 29 with HIZ (37.6%). The high grade of annular
      disruption group shows a high proportion of HIZ on MRI. A positive correlation
      between HIZ and degree of annular disruption was observed. However, no
      correlation between HIZ and positive pain response was established on
      discography. The findings confirm that the presence of HIZ on MRI is only a
      suggestive and screening iconography indication for the diagnosis of discogenic
      LBP and cannot replace the gold standard of the discography. MRI should be
      closely integrated with those of discography, and thus, they play a crucial role
      in selecting operative segments of multilevel lumbar degenerative disk disease.

PMID- 28746178
TI  - Assessment of cytomegalovirus and cell-mediated immunity for predicting outcomes
      in non-HIV-infected patients with Pneumocystis jirovecii pneumonia.
AB  - The clinical importance of pulmonary cytomegalovirus (CMV) co-infection in
      patients with Pneumocystis jirovecii pneumonia (PCP) is uncertain. We therefore
      determined the association of CMV infection with outcomes in non-HIV-infected
      patients with PCP by assessing CMV viral load and CMV-specific T-cell response.We
      prospectively enrolled all non-HIV-infected patients with confirmed PCP, over a 2
      year period. Real-time polymerase chain reaction from bronchoalveolar lavage was
      performed to measure CMV viral load, and CMV enzyme-linked immunospot assays of
      peripheral blood were used to measure CMV-specific T-cell responses. The primary
      outcome was 30-day mortality.A total of 76 patients were finally analyzed. The
      mortality in patients with high BAL CMV viral load (>2.52 log copies/mL, 6/32
      [18%]) showed a nonsignificant trend to be higher than in those with low CMV
      viral load (2/44 [5%], P = .13). However, the mortality in patients with low CMV
      specific T-cell responses (<5 spots/2.0 * 10 PBMC, 6/29 [21%]) was significantly
      higher than in patients with high CMV-specific T-cell response (2/47 [4%], P =
      .048). Moreover, the 2 strata with high CMV viral load and low CMV-specific T
      cell responses (4/14 [29%]) and low CMV viral load and low CMV-specific T-cell
      responses (2/15 [13%]) had poorer outcomes than the 2 strata with high CMV viral
      load and high CMV-specific T-cell responses (2/18 [11%]) and low CMV viral load
      and high CMV-specific T-cell responses (0/29 [0%]).These data suggest that the
      CMV replication and impaired CMV-specific T-cell responses adversely affect the
      outcomes in non-HIV-infected patients with PCP.

PMID- 28746179
TI  - The efficacy and safety of Dl-3n-butylphthalide on progressive cerebral
      infarction: A randomized controlled STROBE study.
AB  - Progressive cerebral infarction (PCI) is associated with high rates of mortality
      and disability. Many studies have shown that Dl-3n-butylphthalide (NBP) is
      effective against acute ischemic stroke. The administration of NBP can result in
      an increased number of capillaries in the ischemic region, promote the
      establishment of collateral circulation, protect the mitochondria, and narrow the
      infarction area, among other effects. In the present study, we evaluated the
      efficacy and safety of NBP for the treatment of PCI.Between March 2008 and May
      2012, we performed a randomized, double-blind placebo-controlled study including
      304 inpatients with PCI. These patients were randomly assigned to the test (152
      cases) and control groups (152 cases). The test group received 200 mg of NBP soft
      capsules orally, 15 minutes before each meal, 3 times daily. The control group
      received 200 mg of placebo soft capsules orally, 15 minutes before each meal, 3
      times daily. Treatment was administered during 21 days. The National Institute of
      Health Stroke Scale (NIHSS) score was assessed before the treatment and on days
      7, 14, 21, and 30 after treatment. The Barthel index (BI) was assessed on the
      same days and on day 90.In the test group, the NIHSS scores on days 7, 14, 21,
      and 30 were 14.75 +/- 4.85, 11.62 +/- 3.49, 8.87 +/- 5.17, and 6.38 +/- 4.93,
      respectively. In the control group, they were 16.08 +/- 3.76, 13.28 +/- 5.02,
      11.05 +/- 4.25, and 8.43 +/- 5.41 (P < .05), respectively. The BI on days 7, 14,
      21, 30, and 90 were 51.57 +/- 15.11, 61.21 +/- 16.39, 70.48 +/- 18.21, 76.41 +/-
      19.02, and 81.10 +/- 15.52 for the test group and 46.79 +/- 18.42, 55.93 +/-
      19.12, 64.84 +/- 17.67, 70.65 +/- 18.54, and 76.54 +/- 17.05 for the control
      group (P < .05), respectively. Adverse events were elevation of alanine
      aminotransferase and aspartate aminotransferase (P > .05).NBP was useful to
      improve the outcome of patients with PCI and decreased their disability for
      activities of daily living. NBP was an efficacious and safe treatment for PCI.

PMID- 28746180
TI  - A CONSORT-compliant prospective randomized controlled trial: radiation dose
      reducing in computed tomography using an additional lateral scout view combined
      with automatic tube current modulation: Phantom and patient study.
AB  - BACKGROUND: Radiation exposure has been a hot point in research field of computed
      tomography (CT). Recently, automated tube current modulation (ATCM) has emerged
      as an important technique to reduce radiation exposure. Many studies have shown
      that the difference in scout view would affect modulation. This prospective
      randomized controlled study is aimed to investigate the impact of an additional
      lateral scout view on radiation dose and image quality in CT using ACTM. METHODS:
      Combined with ATCM (Care Dose 4D) on multidetector CT, 2 thoracic phantom CT
      image series were acquired in which planning was conducted with either an
      anteroposterior (AP) or an AP-lateral scout view. Also, 410 patients underwent
      thoracic CT examinations using Care Dose 4D modulation and were randomized to
      either a scan planned with an AP-lateral scout or a single AP scout. Effects of
      the different scout views on applied effective milliampere seconds (mAs), volume
      CT dose index (CTDIvol) and dose-length-product (DLP) were analyzed. The quality
      of patient CT images was also assessed. Data were analyzed using independent t
      tests and linear correlation analysis. RESULTS: Compared with AP groups, the mean
      CTDIvol (phantom, 0.89 +/- 0.08 vs 1.36 +/- 0.26 mGy, P < .001; in patients, 1.12
      [0.96, 1.34] vs 2.16 [1.66, 2.64] mGy, P < .001) and DLP (in phantom, 26 [23.25,
      28] vs 40 [34.25, 48] mGy*cm, P < .001; in patients, 41 [33, 41] vs 77 [60.5,
      99.5] mGy*cm, P < .001) were significantly reduced by approximately 50% in AP
      lateral scout view group. With the AP-lateral topogram, the radiation dose on
      different off-center positions was essentially equal (CTDIvol: 0.76-0.99 mGy;
      DLP: 22-28 mGy*cm effective dose: 0.31-0. 39 mSv). For image quality, contrast-to
      noise ratio and signal-to-noise ratio values in the AP group were similar to
      those of AP-lateral scout view group. CONCLUSION: AP combined with an additional
      lateral scout view using ACTM can significantly reduce the radiation dose without
      compromising image quality in chest screening CT.

PMID- 28746181
TI  - Efficacy of cataract surgery in patients with uveitis: A STROBE-compliant
      article.
AB  - To evaluate the visual outcomes of cataract surgery in patients with uveitis, and
      to determine risk factors for the recurrence of uveitis and postoperative
      complications.Eighty patients with uveitis who underwent phacoemulsification with
      intraocular lens (IOL) implantation were included in this retrospective study. We
      analyzed the following data: patient characteristics, medications used, visual
      acuity, and complications of cataract surgery.The mean +/- standard deviation
      time from cataract surgery to the last visit was 20.8 +/- 10.4 months. Best
      corrected visual acuity improved significantly after surgery (P < .001). The
      visual outcome was worse in patients with Behcet disease than in patients with
      other etiologies of uveitis. Gender (P = .018) and IOL type (P = .020) were
      significantly associated with recurrent uveitis after surgery. The incidence of
      recurrent inflammation was not significantly different between patients who did
      or did not receive systemic therapy (P = .43). Perioperative systemic therapies
      (P = .011) and recurrent uveitis within 3 months of surgery (P = .043) were
      associated with posterior capsular opacification. Perioperative systemic
      therapies (P = .026) and recurrent uveitis after surgery (P = .006) were also
      significantly associated with cystoid macular edema.Patients with uveitis could
      benefit from cataract surgery. Patients with Behcet disease had worse
      postoperative prognosis than patients with other etiologies of uveitis. A heparin
      surface-modified IOL may reduce the incidence of recurrent inflammation.

PMID- 28746182
TI  - Plumbagin-loaded aptamer-targeted poly D,L-lactic-co-glycolic acid-b-polyethylene
      glycol nanoparticles for prostate cancer therapy.
AB  - Plumbagin inhibits the growth, metastasis, and invasion of prostate cancer (PCa).
      However, its lower bioavailability limits biopharmaceutical properties due to
      insolubility in water. Prostate-specific membrane antigen (PSMA) aptamer-targeted
      nanoparticles (NPs) significantly enhanced cytotoxicity in prostate epithelial
      cells. This study aimed to investigate the effects of plumbagin-loaded prostate
      specific membrane antigen (PSMA) aptamer-targeted poly D,L-lactic-co-glycolic
      acid-b-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) on prostate cancer
      (PCa) in vitro.PLGA-PEG with a terminal carboxylic acid group (PLGA-PEG-COOH) was
      synthesized, and plumbagin was loaded on PLGA-PEG-COOH NPs using the
      nanoprecipitation method and characterized by field emission scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), and laser light
      scattering. The uptake and distribution of plumbagin-NPs in human PCa LNCaP cells
      were investigated by fluorescent labeling. Subsequently, PSMA antibody-targeted
      PLGA-PEG-COOH NPs (targeted NPs) were prepared by covalent binding and
      characterized by x-ray photoelectron spectroscopy. Furthermore, the anticancer
      activity of plumbagin-loaded, targeted NPs was compared with that of nontargeted
      NPs in LNCaP cells in vitro.Plumbagin-NPs (diameter of 189.4 +/- 30.6 nm and zeta
      potential of -17.1 +/- 3.7 mV) were optimized based on theoretical drug loading
      of 5% and a ratio of water:acetone of 3:1. During the first 2 hours, the
      cumulative release rate of the drug was 66.4 +/- 8.56%. Moreover, plumbagin
      targeted NPs with nitrogen atoms were prepared. The uptake rate was 90% at 0.5
      hours for targeted and nontargeted NPs. The IC50 of targeted NPs and nontargeted
      NPs was 32.59 +/- 8.03 MUM and 39.02 +/- 7.64 MUM, respectively.Plumbagin-loaded
      PSMA aptamer-targeted NPs can be used in targeted chemotherapy against PCa.

PMID- 28746183
TI  - Visual outcomes after balanced salt solution infiltration during lenticule
      separation in small-incision lenticule extraction for myopic astigmatism.
AB  - To evaluate the refractive outcomes of balanced salt solution infiltration during
      small-incision lenticule extraction (SMILE).This randomized prospective study
      enrolled 52 patients (104 eyes) with myopic astigmatism. Patients underwent SMILE
      to correct the myopic astigmatism in Daping Hospital of the Third Military
      Medical University between January and July 2013. One eye of each patient
      received traditional SMILE (control group) and the other received a modified
      SMILE procedure (liquid infiltration group). The corrected distance visual acuity
      (CDVA), postoperative uncorrected distance visual acuity (UDVA), refraction,
      wavefront aberration, intraocular pressure (IOP), modulation transfer function
      (MTF) cut-off frequency, and objective scattering index (OSI) were evaluated.UDVA
      in the liquid infiltration group was significantly higher than that in the
      control group at 1 day postoperatively, but not at 1 month after surgery.
      Moreover, OSI and MTF cut-off frequency in the liquid infiltration group were
      higher than those in the control group at early follow-up. However, no
      significant intergroup difference was observed in the OSI and MTF cut-off
      frequency at 3 months after surgery. In addition, the predictability was better
      in the liquid infiltration group than in the control group. The changes of
      horizontal coma in the liquid infiltration group were lesser than those in the
      control group. However, no intergroup difference was observed in the reduction of
      IOP at 1 month after surgery.The modified SMILE procedure results in better
      visual outcomes than did the traditional SMILE procedure when used for treating
      myopic astigmatism.

PMID- 28746184
TI  - Theoretical mechanism of temporary renal function improvement after abdominal
      aortic aneurysm surgery: Applications for clinical imaging and laboratory data.
AB  - We evaluated the effects of changes in blood flow due to abdominal aortic
      aneurysm (AAA) surgery by using a simple zero-dimension model and applied
      theoretical values to clinical data.The zero-dimension electronic circuit model
      and diagram of blood flow distribution were created by setting the resistance of
      the aorta, bilateral iliac arteries, renal arteries, and aneurysm. Resistance of
      the aneurysm and resistance of the aorta before surgery were compared with that
      of the aorta after surgery. We set the radius length of each anatomical parameter
      to calculate theoretical values.Renal flow increased 13.4% after surgery. Next,
      we analyzed contrast-enhanced computed tomography data of 59 patients who
      underwent AAA surgery. A total of 19 patients were treated with a Y graft and 7
      patients were treated with a straight graft during open surgery. However, 33
      patients were treated with a bifurcated stent graft. A significant linear
      relationship between the increased estimated glomerular filtration rate (eGFR)
      ratio and the decreased aneurysm ratio was found only for the straight graft
      group.Using a circuit model, renal blood flow theoretically increased after AAA
      surgery. Clinically, there was a correlation between volume regression and eGFR
      improvement only in the limited AAA group.

PMID- 28746185
TI  - Clinical significance of delta neutrophil index in the differential diagnosis
      between septic arthritis and acute gout attack within 24 hours after
      hospitalization.
AB  - The most important differential diagnoses of acute monoarticular arthritis are
      septic arthritis and acute gout attack. Identifying infection is crucial in
      preventing the devastating outcome of septic arthritis. The delta neutrophil
      index (DNI) is a value that corresponds to the fraction of circulating immature
      granulocytes. As DNI reflects the burden of infection, we evaluated this index as
      a differentiating marker between septic arthritis and acute gout attack.The
      medical records of 149 patients with septic arthritis and 194 patients with acute
      gout attack were reviewed. A specific cell analyzer, ADVIA 2120, was used to
      measure DNI. Clinical and laboratory markers associated with predicting septic
      arthritis were assessed by using logistic regression.Patients with septic
      arthritis showed higher levels of DNI than those with acute gout attack (3.3 vs
      0.6%, P < .001). Similar results were observed in patients without monosodium
      urate (MSU) crystal confirmation or those with normouricemia (3.3 vs 0.5 and 3.1
      vs 0.7%, respectively; P < .001 for both). A DNI level of 1.9% was determined as
      the cutoff value for predicting septic arthritis. In the multivariate analysis,
      DNI was the most powerful independent value for predicting septic arthritis (odds
      ratio 14.003).This study showed the possibility of using DNI as a differentiating
      marker between septic arthritis and acute gout attack at the crucial early phase.
      DNI showed its relevance regardless of confirmation of MSU crystal deposition or
      serum level of uric acid.

PMID- 28746186
TI  - Laparoscopic-based score assessment combined with a multiple disciplinary team in
      management of recurrent ovarian cancer: A single-center prospective study for
      personalized surgical therapy.
AB  - The aim of the study was to evaluate the effect of laparoscopic-based score
      combined with a multiple disciplinary team (MDT) for predicting optimal
      cytoreduction and perform personalized surgical treatment in recurrent ovarian
      cancer (ROC).The study is a single-center, prospective investigation. From March
      2013 to May 2015, the consecutive treated patients with platinum-sensitive ROC
      were collected in Yangpu Hospital. The appropriated patients were enrolled into
      the study to perform the laparoscopic-based PIV (predictive index value) score
      assessment with an MDT for predicting optimal cytoreduction. The PIV cutoff value
      was confirmed to be 8. Patients of PIV <8 received laparoscopic/laparotomy
      secondary surgery following chemotherapy, and the ones with PIV >=8 did
      chemotherapy alone. Sensitivity, specificity, positive predicted value (PPV),
      negative predicted value (NPV), and overall accuracy for each range of PIV score
      were calculated. All recruited patients participated in follow-up observation.
      Overall survival was recorded.In total, 58 eligible ROC patients received
      laparoscopy assessment. Forty-one patients of PIV <8 received secondary
      cytoreductive surgeries. Twenty-three (23/41 56.1%) attained optimal
      cytoreduction. However, 8 of 23 achieved completed cytoreduction. Also, 17
      patients of PIV >=8 underwent chemotherapy alone. Sensitivity, specificity, PPV,
      NPV, and overall accuracy for PIV >=8 were 60%, 100%, 100%, 25%, and 64.7%,
      respectively. Overall survival in patients performing optimal cytoreduction was
      significantly higher than in those undergoing suboptimal cytoreduction or
      chemotherapy alone (45.9 +/- 2.5 vs 36.7 +/- 4.3 months, P = .047; 45.9 +/- 2.5
      vs 35.8 +/- 3.4 months, P = .027).Laparoscopic-based score assessment plus MDT
      helps to identify the appropriate patients to perform optimal secondary
      cytoreduction and provide a personalized surgical approach in management of ROC.

PMID- 28746187
TI  - Research of cerebral activation in Uygur-speaking and Chinese-speaking
      participants during verb generation task with functional magnetic resonance
      imaging.
AB  - The aims are to investigate and compare the activated cerebral regions of Uygur
      speaking and Chinese-speaking participants during verb generation task.A total of
      31 cases of Uygur and 28 cases of Han healthy volunteers were enrolled. They were
      requested to take verb generation tasks. Blood oxygenation level-dependent
      functional magnetic resonance imaging (BOLD-fMRI) was performed. The fMRI images
      were collected and activated brain regions were analyzed.In Chinese-speaking
      participants, the main activated cerebral regions were as follows: the left
      caudate nucleus, the left occipital gyrus, the left fusiform gyrus, bilateral
      supplementary motor area (BA8/ 6), the left BA32, left precuneus, the left
      superior parietal lobule, the left inferior parietal lobule (BA7), the left
      angular gyrus, the right side of the central gyrus (BA9), the left inferior
      frontal gyrus triangular section, the right pars opercularis gyri frontalis
      inferiorista, and bilateral cerebellum. In Uygur-speaking subjects, the main
      activated cerebral regions included left precentral gyrus (BA9 region), inferior
      frontal gyrus of left opercular part, inferior frontal gyrus of left triangle
      part, and left cerebellum. Left caudate nucleus, left orbital frontal gyrus,
      right caudate nucleus, and bilateral anterior cingulate gyrus (BA32 region) of
      Chinese group were significantly activated compared with Uygur group. By
      contrast, Uygur group showed no region that was more activated than Chinese
      group.The present study demonstrates that activated brain regions in verb
      generation tasks are different between Uygur and Chinese languages. Processing of
      Uygur characters is mainly in the left hemisphere of the brain, while the
      processing of Chinese characters needs more participation by the right hemisphere
      of the brain.

PMID- 28746188
TI  - Antenatal diagnosis and prognostic factors of aneurysmal malformation of the vein
      of Galen: A case report and literature review.
AB  - RATIONALE: Vein of Galen aneurysmal malformation (VGAM) is a rare complex
      malformation of the cerebral vascular system consisting of arteriovenous shunts
      between the vein of Galen and the cerebral arteries. PATIENT CONCERNS: We present
      the case of a 31-year-old pregnant woman, para 1, gravida 1. DIAGNOSES: At 26
      weeks' gestation who was examined for an anechoic mass on the cerebral median
      midline with color and pulsed Doppler. She presented with positive flow on the
      color and pulsed Doppler test, associated with hydrocephalus, cortical
      hypoplasia, cardiomegaly, jugular vein distension. INTERVENTIONS: No intervention
      for VGAM was done. OUTCOMES: This case of a VGAM was associated with negative
      prognostic factors. LESSONS: The ultrasound color Doppler together with the 3D
      power Doppler allowed reconstruction of the vascular connections and of the
      relationship of these with other anatomical structures, which contributed to
      establishing the prognosis.

PMID- 28746189
TI  - Early prediction of infected pancreatic necrosis secondary to necrotizing
      pancreatitis.
AB  - To assess the association between the clinical parameters within 48 hours of
      admission and the occurrence of infected pancreatic necrosis (IPN) during the
      late phase of necrotizing pancreatitis (NP).All patients were divided into 2
      groups, the IPN and non-IPN groups. The clinical data were retrospectively
      analyzed. Univariate and multivariate logistic regression analyses were performed
      to evaluate the relationship between clinical parameters and IPN secondary to NP.
      The performance of each independent variable was plotted by the receiver
      operating characteristic (ROC) curve. Consequently, the cut-off level of each
      independent variable with its sensitivity and specificity was calculated.A total
      of 215 patients were enrolled in our study. Among them, 87 (40.5%) patients
      developed IPNs after a median of 13.5 (9.5-23.0) days from admission.
      Multivariate analysis indicated that the level of hematocrit (HCT) from 40% to
      50% (P=.012, odds ratio (OR) = 2.407), HCT over 50% (P < .009, OR = 6.794), blood
      urea nitrogen (BUN) (P = .040, OR = 1.894), C-reactive protein (CRP) (P = .043,
      OR = 1.837), and procalcitonin (PCT) (P = .002, OR = 2.559) were independent risk
      factors of IPN secondary to NP. The ROC cures revealed that the area under the
      ROC (AUC) of the maximum level of HCT, BUN, CRP, and PCT within 48 hours of
      admission was 0.687, 0.620, 0.630, and 0.674 respectively. Furthermore, the
      combination of these 4 individual parameters contributes to a more preferable AUC
      of 0.789 with a sensitivity of 67.8% and specificity of 77.3%.The maximum levels
      of PCT, CRP, HCT, and BUN within 48 hours of admission are independent factors of
      IPN and their combination might accurately predict the occurrence of IPN
      secondary to NP.

PMID- 28746190
TI  - VASA mRNA (DDX4) detection is more specific than immunohistochemistry using poly-
      or monoclonal antibodies for germ cells in the male urogenital tract.
AB  - VASA, also known as DDX4, is reported to be specifically expressed in cells
      belonging to the germ cell lineage, both in males and females. Therefore, it
      could be an informative protein biomarker to be applied on semen to differentiate
      between obstructive and nonobstructive azoospermia (OA and NOA, respectively). In
      addition, it could be of value to predict sperm retrieval based on testicular
      sperm extraction. Immunocytochemistry of proven OA semen using both polyclonal
      and monoclonal antibodies against VASA showed positive staining of both cells and
      cell sized particles. This is spite of being the absolute negative controls,
      completely lacking germ lineage derived cells and material. In order to identify
      the source of the VASA-positive material, a detailed screen of different
      anatomical parts of the whole male urogenital tract was performed of multiple
      cases using immunohistochemistry.The polyclonal antibody stained, besides the
      expected germ cells in the testis, epithelium of the bladder and the seminal
      vesicles. The monoclonal antibody only stained the latter. To investigate whether
      the immunohistochemical staining is associated with the presence of the
      corresponding VASA mRNA, samples of seminal vesicles, bladder, testis, and semen
      (with and without germ cells) were investigated using the specific quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR) on 42 samples. A
      positive result was detected in testis and semen containing germ cells (n = 10
      and 8), being negative in semen without germ cells (n = 11), bladder (n = 3), and
      seminal vesicles (n = 10).Two commercially available VASA antibodies (mono- and
      polyclonal) are not specific. In contrast, VASA-mRNA evaluation, using qRT-PCR,
      is specific for the presence of germ cells, therefore, is an interesting
      molecular biomarker for germ cell detection in semen.

PMID- 28746191
TI  - Whole exome sequencing unveils a frameshift mutation in CNGB3 for cone dystrophy:
      A case report of an Indian family.
AB  - RATIONALE: Genetic elucidation of cone-dominated retinal dystrophies in Indian
      subcontinent is much needed to identify and catalog underlying genetic defects.
      In this context, the present study recruited a consanguineous Indian family
      affected with autosomal recessive cone dystrophy (CD). Considering the huge
      genetic heterogeneity and recessive inheritance of the disease, we chose to
      dissect out causal variant in this family by whole exome sequencing (WES).
      PATIENT CONCERNS: In the recruited family, three of the six siblings had
      complaints of poor visual acuity, photophobia, and disturbed colour vision since
      early childhood. Fundus examination disclosed vascular attenuation and macular
      retinal pigment epithelium (RPE) changes in all the affected siblings, signifying
      degeneration of photoreceptor cells. DIAGNOSIS: Complete clinical investigation
      and electroretinography studies led to the diagnosis of cone dystrophy in three
      siblings of the family. INTERVENTIONS: Detailed ophthalmic examination, including
      family history, visual function testing, and retinal imaging, was performed. We
      captured and sequenced exomes of 2 affected siblings and their mother using
      SureSelect Human All Exon V5 Kit on Illumina HiSeq 2000/2500 platform with 100 bp
      paired-end sequencing method. Candidates after data analysis were screened by
      segregation analysis and Sanger sequencing. Considering recessive inheritance and
      consanguinity in the pedigree, we attempted to map large loci homozygous by
      descent in the genome of patients using exome sequencing variants. Extensive
      protein modeling was carried out to assess possible consequences of the
      identified variant on the 3-dimensional structure of the protein. OUTCOMES: WES
      generated more than 65,000 variants for each individual. Assuming recessive
      inheritance, 13,026 variants were selected. Further filtering on the basis of
      their position in gene, class, and minor allele frequency constricted the huge
      list to 12 rare variants. Finally, we ascertained a single base deletion
      c.1148delC (p.Thr383fs) in the gene CNGB3 as the causal variant. This is a
      recurrent frameshift mutation resulting in truncated CNGB3 protein. We mapped a
      large 15-Mb stretch of homozygous markers spanning the causal variant in the
      proband. The gene CNGB3 encodes modulatory subunit of cyclic nucleotide-gated
      channels in cone photoreceptors. Protein modeling reveals loss of 2 transmembrane
      helices and conserved CAP_ED domain in truncated CNGB3, which eventually is
      predicted to form nonfunctional channels and hamper phototransduction. LESSONS:
      We have identified a recurrent mutation c.1148delC (p.Thr383fs) in CNGB3 for
      autosomal recessive CD. The present report provides the first description of
      CNGB3 mutation from India. It is also the foremost investigation of familial CD
      in Indian patients; therefore, it presents the primary genetic etiology of CD in
      India.

PMID- 28746192
TI  - Serum vaspin level as a predictive indicator in the amelioration of fatty liver
      and metabolic disturbance in patients with severe obesity after laparoscopic
      vertical banded gastroplasty.
AB  - BACKGROUND: This study is all about predicting the value of serum vaspin level in
      the amelioration of fatty liver and metabolic disturbance in patients with severe
      obesity after laparoscopic vertical banded gastroplasty (LVBG). METHODS: A total
      of 164 patients (from January 2012 to May 2015) with severe obesity were chosen
      and performed LVBG. Enzyme-linked immunosorbent assay was performed to detect the
      serum vaspin level. The patients were given a biochemical automatic analyzer to
      measure the biochemical indicators. Homeostasis model assessment (HOMA) helps in
      the calculation of fasting insulin level (FINS) and insulin resistance (IR). The
      changes in fatty liver were examined by computed tomography (CT). Receiver
      operating characteristic curve is used to increase the predictive value of serum
      vaspin level in the amelioration of liver function and disturbances in the
      metabolism. RESULTS: Weight, BMI, waist circumference, serum vaspin level, and
      triglyceride (TG) decreased, but CT value of liver increased at 4th, 7th, and
      12th month after surgery. After the 7th and 12th month period of surgery, the
      alanine aminotransferase, aspartate aminotransferase, FINS, and HOMA-IR reduced
      in the patients (P <.005). The area under ROC curve (AUC) is about 0.871 +/-
      0.031 with 95%CI of 0.810-0.931 (P <.001). The sensitivity, specificity, and
      accuracy of serum vaspin level <=0.9 were 87.80%, 78.05%, and 83.28%,
      respectively. BMI, FINS, and serum vaspin level <=0.9 were the influencing
      factors of the amelioration of fatty liver and metabolic disturbance. CONCLUSION:
      This study proves that the serum vaspin level serves as a predictive indicator in
      the amelioration of fatty liver and metabolic disturbance in patients with severe
      obesity after LVBG.

PMID- 28746193
TI  - Comparing common doses (double-dose vs usual-dose) of atorvastatin for preventing
      contrast-induced acute kidney injury and mortality after coronary angiography.
AB  - High-dose atorvastatin pretreatment was proved reducing the risk of contrast
      induced acute kidney injury (CI-AKI), especially in patients with high C-reactive
      protein (CRP) levels. We evaluated the effects of common atorvastatin doses
      (double vs usual) on the risk of CI-AKI and mortality.We recorded outcomes from
      1319 patients who were administered periprocedural common doses of atorvastatin.
      The risks of CI-AKI and mortality between double-dose (40 mg/d) and usual-dose
      atorvastatin (20 mg/d) were compared using multivariable regression models in all
      patients or CRP tertile subgroups.Seventy-six (5.8%) patients developed CI-AKI.
      Double-dose atorvastatin compared with usual-dose did not further reduce the risk
      of CI-AKI (adjusted odds ratio [OR]: 2.28, 95% confidence interval [CI]: 0.92
      5.62, P = .074), even for patients in the highest CRP tertile (>8.33 mg/L;
      adjusted OR: 3.76, 95% CI: 0.83-17.05, P = .086). Similar results were observed
      in reducing mortality in all patients (adjusted hazard ratio: 0.47, 95% CI: 0.10
      2.18; P = .339) and in the highest CRP tertiles (P = .424). In the subgroup
      analysis, double-dose atorvastatin increased risk of CI-AKI in patients with
      creatinine clearance (CrCl) < 60 mL/min, anemia, contrast volume > 200 mL and > 2
      stents implanted (P = .046, .009, .024, and .026, respectively).Daily
      periprocedural double-dose atorvastatin was not associated with a reduced risk of
      CI-AKI compared with usual-dose, and did not provide an improved long-term
      prognosis, even in patients with high CRP levels. However, it increased the risk
      of CI-AKI in patients with a high contrast volume/CrCl.

PMID- 28746194
TI  - 18F-FDG PET/CT is an ideal imaging modality for the early diagnosis of relapsing
      polychondritis: A case report.
AB  - BACKGROUND: Relapsing polychondritis (RP) is a rare autoimmune disease of unknown
      etiology that may affect multiple cartilage throughout the body. CASE REPORT: We
      report on a middle-aged man presented with cough, chest tightness, and fever of
      unknown origin, 18F-fluorodeoxyglucose positron emission tomography/computed
      tomography (F-FDG PET/CT) was performed. And the imaging shows multiple increased
      FDG accumulation in tracheobronchial tree and all intercostal cartilages, as well
      as in nasal, right auricule, laryngeal cartilage. Based on the findings, the
      diagnosis of RP was made. CONCLUSION: Our case demonstrates that FDG PET/CT is an
      useful diagnostic tool to accurately determine the extent of inflammation
      throughout the body and to guiding the selection of a biopsy site.

PMID- 28746195
TI  - The immediate effect of facial candling on inflammatory mediators, substance P,
      symptoms severity, and quality of life in allergic rhinitis patients: Study
      protocol for a randomized controlled trial.
AB  - INTRODUCTION: Asian countries have a variety of ethnic groups and culture that
      provide their own traditional treatment in health care. Facial candling appears
      to be one of the popular traditional treatments in Southeast Asian. The
      complementary medicine practitioners promote that the facial candling treatment
      would help in reducing the symptoms of allergic rhinitis and other problems
      related to sinus. Due to the lack of evidence available, the effectiveness of
      this treatment method and its mechanism, however, remains unknown. The objective
      of this research is therefore to study impact of facial candling on inflammatory
      mediators, substance P (SP), symptoms severity, and quality of life (QoL) in
      allergic rhinitis patients. METHOD AND ANALYSIS: A randomized, nonblinded,
      controlled trial will be carried out by recruiting a total of 66 eligible
      allergic rhinitis patients who fulfill the inclusion criteria from a university
      health center. The subjects will be randomly assigned into 2 groups: intervention
      group receiving facial candling treatment and control group (no treatment given).
      Samples of blood and nasal mucus will be collected right before and after
      intervention. Samples collected will be analyzed. The primary outcomes are the
      changes in the level of SP in both blood and mucus samples between both groups.
      The secondary outcomes include the levels of inflammatory mediators (ie, tumor
      necrosis factor alpha, interleukin (IL)-3, IL-5, IL-6, IL-10, and IL-13) and the
      severity of allergic rhinitis symptoms as measured by a visual analogous scale
      and QoL using the Rhinitis Quality of Life Questionnaire (RQLQ). ETHICAL AND
      TRIAL REGISTRATION: The study protocols are approved from the Ethical and
      Research Committee of the Universiti Teknologi MARA (REC/113/15). The trial is
      registered under the Australia New Zealand Clinical Trial Registry
      (ACTRN12616000299404). The trial was registered on 03/07/2016 and the first
      patient was enrolled on 10/12/2016. CONCLUSION: Facial candling is one of the
      unique treatments using candles to reduce the severity of symptoms and
      inflammation. This is the first ever study conducted on facial candling that will
      give rise to new knowledge underlying the effects of facial candling on severity
      of symptoms and inflammation relief mechanism mediated by substance P and
      inflammatory mediators.

PMID- 28746196
TI  - Retrospective review of laparoscopic versus open surgery in the treatment of
      appendiceal abscess in pediatric patients: Laparoscopic versus open surgery for
      appendiceal abscess.
AB  - Laparoscopic appendectomy (LA) has become well accepted, but the role of LA for
      appendicitis upon presentation with an abscess remains undefined. This study was
      to assess the postoperative recovery and complications following LA in pediatric
      patients with appendiceal abscess in comparison with open appendectomy (OA).We
      conducted a retrospective review of patients presented with appendiceal abscess
      between 2005 and 2016. Propensity score matching (PSM) was conducted to adjust
      for any potential selection bias for the surgical approaches. In 108 matched
      patients, operative outcomes and surgical complications were evaluated based on
      LA or OA.The patients with LA experienced prompt postoperative gastrointestinal
      function recovery, like first bowel movement (risk ratio [RR], 0.52; 95%
      confidence interval [CI], 0.44-0.69; P < .001), so spend the lower mean length of
      hospitalization (RR, 0.53; 95% CI, 0.41-0.76; P < .001) in comparison with
      patients with OA. Furthermore, the immunologic and inflammatory variable white
      blood cell (WBC) (RR, 0.56; 95% CI, 0.46-0.73; P < .001) and C-reactive protein
      (CRP) (RR, 0.58; 95% CI, 0.43-0.86; P = .011) on postoperative days (POD) 5 was
      reduced in patients undergone LA compared with that of OA. A lower overall
      postoperative complication rate, including surgical wound infection (odds ratio
      [OR], 0.38; 95% CI, 0.18-0.81; P = .008) and incision dehiscence (OR, 0.06; 95%
      CI, 0.01-0.45; P < .001) was noted in patients with LA compared with OA.LA was
      feasible and effective for appendicitis upon presentation with an abscess and
      associated with beneficial clinical effects, such as postoperative
      gastrointestinal function recovery and reduced postoperative complications. LA
      should be seriously considered as the first line procedure of choice.

PMID- 28746197
TI  - Role of thymic stromal lymphopoietin in the pathogenesis of lumbar disc
      degeneration.
AB  - BACKGROUND: This study aims to investigate the role of thymic stromal
      lymphopoietin (TSLP) in the pathogenesis of lumbar disc degeneration (LDD).
      METHODS: Nucleus pulposus tissues were collected from 77 LDD patients (the case
      group), in addition, normal tissues were extracted from 21 patients suffering
      from lumbar fractures (the control group). Immunohistochemistry was applied in
      order to detect TSLP positive expression. In accordance with varying
      transfection, the cells were divided into TSLP-siRNA, TSLP-siRNA + TSLPR-siRNA,
      control, blank, anti-TSLPR, and IgG groups. Western blotting was used in order to
      detect TSLP expression in tissues, and TSLP and type II collagen (COL2AL) in cell
      culture media were detected using enzyme linked immunosorbent assay (ELISA). Cell
      viability was measured using a MTT assay. Aggrecan levels were detected using
      antonopulos, and cell apoptosis was determined using flow cytometry. RESULTS:
      TSLP-positive expression was found to be significantly higher in the case group
      compared with the control group. LDD patients' Pfirrmann grades and preoperative
      visual analogue scale (VAS) scores were associated with TSLP-positive rate. Cells
      transfected with TSLP-siRNA and TSLPR-siRNA plasmids exhibited lower TSLP and
      thymic stromal lymphopoietin receptor (TSLPR) protein expression compared with
      the control and blank groups. Compared with the control and blank groups, there
      was significantly higher cell viability, lower cell apoptosis, and higher COL2AL
      and Aggrecan levels in the TSLP-siRNA, anti-TSLPR, and TSLP-siRNA+TSLPR-siRNA
      groups; there were significant differences between the TSLP-siRNA, anti-TSLPR,
      and TSLP-siRNA+TSLPR-siRNA groups and IgG group (all P < .05) CONCLUSION:: Our
      study provides evidence for the hypothesis that TSLP could reflect the
      histological severity of LDD, and TSLP-siRNA and, TSLPR-siRNA could inhibit
      apoptosis of nucleus pulposus cells. The evident information obtained from the
      investigation could lead the way for new therapeutic approaches regarding LDD
      treatment.

PMID- 28746198
TI  - Radiation reduction during percutaneous coronary intervention: A new protocol
      with a low frame rate and selective fluoroscopic image storage.
AB  - The percutaneous coronary intervention (PCI) procedure is associated with
      potentially high levels of radiation exposure and therefore increased risk of
      adverse radiation-induced outcomes, ranging from cataract to malignancy. Frame
      rate reduction and selective fluoroscopy storage may help reduce radiation
      exposure. In this study, we evaluated the efficacy of a radiation reduction
      protocol that uses a lower frame rate and selective storage of fluoroscopic
      images in terms of its effect on reducing the radiation dose during PCI.The new
      protocol incorporated a lower frame rate as compared with the conventional
      protocol, and used selective storage of fluoroscopic images. We reviewed the
      medical records of patients who underwent PCI under the conventional protocol
      from January 2013 to December 2013, and compared them with those who underwent
      PCI with the new protocol from January 2015 to December 2015. The primary
      endpoint was radiation dose reduction expressed as cumulative air kerma and dose
      area product (DAP). The image quality was assessed by 3 independent well-trained
      cardiologists.One hundred fifty-five patients were enrolled in the conventional
      protocol group, and 152 were enrolled in the radiation reduction protocol group
      (total, n = 307). There was no statistical significance in terms of the baseline
      characteristics, including body mass index. Overall, the radiation reduction
      protocol group showed a significant reduction in both cumulative air kerma
      (1634.39 +/- 717.95 vs 2074.75 +/- 1003.72 mGy, P < .001) and DAP (12344.86 +/-
      5371.75 vs 15312.19 +/- 7136.58 MUGy m, P < .001). Image quality was acceptable
      in both groups.The radiation reduction protocol, which uses a lower frame rate
      and selective storage of fluoroscopic images, may be an alternative approach to
      reducing PCI radiation dose.

PMID- 28746199
TI  - 18F-FDG PET/CT imaging of atypical subacute thyroiditis in thyrotoxicosis: A case
      report.
AB  - BACKGROUND: In addition to its established role in oncologic imaging, F
      fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG
      PET/CT) is useful for the assessment of inflammatory activity. However, subacute
      thyroiditis (SAT) in thyrotoxicosis is rarely detected during these scans. CASE:
      A 66-year-old man with SAT in thyrotoxicosis demonstrated symptoms of transient
      fatigue, headache, and fever, without typical neck pain. Using F-FDG PET/CT, we
      found increased F-FDG uptake in the thyroid gland, predominantly in the right
      side due to SAT. We also observed a coexisting decrease in F-FDG uptake in the
      liver and increased F-FDG uptake in skeletal muscle due to thyrotoxicosis.
      CONCLUSION: Using F-FDG PET/CT, the combined observations of increased F-FDG
      uptake in the thyroid and skeletal muscle, and decreased F-FDG uptake in the
      liver, even when the typical symptom of neck pain is subtle or absent, may be
      helpful for the differential diagnosis of SAT in thyrotoxicosis.

PMID- 28746200
TI  - Promising significance of the association of miR-204-5p expression with
      clinicopathological features of hepatocellular carcinoma.
AB  - Decreased level of miR-204-5p has been documented in various malignancies.
      However, the expression and clinical significance of miR-204-5p in hepatocellular
      carcinoma has not been investigated. The aim of this study is to examine the
      relationship between miR-204-5p expression and clinicopathological features in
      hepatocellular carcinoma (HCC) as well as to predict the relevant signaling
      pathways. The miR-204-5p expression level was detected in HCC and in matched
      paraneoplastic liver from 95 formalin-fixed paraffin-embedded tissues by the real
      time reverse transcription polymerized chain reaction (qRT-PCR). The association
      of miR-204-5p expression with clinicopathological features as well as the
      prognosis of HCC was examined. Public data portals including the Gene Expression
      Omnibus and The Cancer Genome Atlas were used to retrieve the HCC-related data in
      order to perform a comprehensive meta-analysis. Meanwhile, protein-protein
      interaction (PPI) and enrichment analyses were performed using predicted target
      genes. The relative expression of miR-204-5p was remarkably reduced in HCC than
      that in paraneoplastic hepatic tissues. In HCC, the miR-204-5p expression was
      downregulated in the metastasis, vasoinvasion, and advanced stage (III and IV)
      subgroups compared with their counterparts. Furthermore, the meta-analysis based
      on qRT-PCR data demonstrated that miR-204-5p was markedly downregulated in HCC
      with a standardized mean difference of -5.19 (P < .001). However, no significant
      association was observed between miR-204-5p and survival outcomes. The potential
      target genes of miR-204-5p were significantly enriched in several pathways which
      might be associated with HCC, such as "cell proliferation" from GO terms and
      "pathways in cancer" from the KEGG analysis. A PPI network of miR-204-5p
      potential target genes identified prospective core genes potentially involved in
      the regulation of HCC oncogenesis and progression. Our findings suggested that
      miR-204-5p might act as a tumor-suppressive gene in the tumorigenesis and
      progression of HCC via vital signaling pathways and that miR-204-5p could be
      regarded as a protective factor in HCC.

PMID- 28746201
TI  - A rare case of iron-pill induced gastritis in a female teenager: A case report
      and a review of the literature.
AB  - RATIONALE: The treatment of iron-deficiency anemia with oral iron supplements can
      present side-effects on the GI tract mucosa including necrosis, ulceration, or
      ischemia. The particular endoscopic findings and the histopathological exam will
      establish the diagnosis of erosive gastritis with iron deposits in the gastric
      mucosa. PATIENT CONCERNS: We present the case of a 14-year-old female admitted in
      our clinic for upper digestive hemorrhage, nausea, melena, and abdominal pain.
      Her personal history revealed iron deficiency anemia receiving oral iron
      supplements for approximately 2 weeks. DIAGNOSIS: The laboratory tests at the
      moment of admission pointed out anemia, increased level of serum iron, increased
      liver transaminases, a decreased level of ferritin, but with normal levels of
      both total iron-binding capacity and transferrin. INTERVENTIONS: The eso-gastro
      duodenoscopy revealed multiple brown deposits on the surface of the gastric
      mucosa and multiple hemorrhagic lesions, under the aspect of erosions all over
      the gastric mucosa, but more severe in the antral part, and the histopathological
      exam confirmed the presence of iron deposits at this level. CONCLUSION: Iron-pill
      induced gastritis is a rare, under-diagnosed entity that can be present even at
      pediatric ages with potential severe clinical impact.

PMID- 28746202
TI  - Assessing diagnostic value of contrast-enhanced ultrasound and contrast-enhanced
      computed tomography in detecting small hepatocellular carcinoma: A meta-analysis.
AB  - BACKGROUND: This study aimed to compare the diagnostic values of contrast
      enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) in
      detecting small hepatocellular carcinoma (SHCC). METHODS: A series of related
      articles from 2001 to 2015 were searched in PubMed and Embase databases. Data
      from selected articles were pooled to analyze the sensitivity, specificity,
      positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds
      ratio (DOR), and summary receiver operating characteristic (SROC) curve using
      Meta-DiSc software. Heterogeneity was estimated using chi-based Cochran-Q test
      and I-statistics, and publication bias was estimated using Egger test in Stata
      software. RESULTS: In total, 8 high-quality articles based on 623 subjects
      including 318 SHCC cases were included. For the extracted data, no heterogeneity
      and publication bias were observed among these studies. The following respective
      data on CEUS and CECT were pooled: sensitivities: 0.75 (95% confidence interval
      [CI]: 0.70-0.80) and 0.74 (95% CI: 0.68-0.78); specificity: 0.91 (95% CI: 0.87
      0.94) and 0.92 (95% CI: 0.89-0.95); PLRs: 5.99 (95%CI: 3.28-10.92) and 7.76 (95%
      CI: 3.12-19.28); NLRs: 0.31 (95% CI: 0.20-0.49) and 0.32 (95% CI: 0.20-0.50);
      DORs: 27.38 (95% CI: 14.38-52.11) and 30.02 (95% CI: 9.32-96.62). Area under the
      SROC curve: 0.91 and 0.89 and no significant statistical result was identified
      between them (Z = 0.23, P = .82). CONCLUSION: CEUS showed a diagnostic ability
      comparable to that of CECT in detecting SHCC.

PMID- 28746203
TI  - The FTO rs9939609 polymorphism is associated with short leukocyte telomere length
      in nonobese individuals.
AB  - The fat mass and obesity-associated (FTO) rs9939609 polymorphism have been
      associated with the increased metabolic risk and mortality, irrespective of
      obesity. The mechanism underlying this association is not known. We aimed to
      evaluate whether the FTO rs9939609 risk variant is independently associated with
      metabolic risk factors and/or leukocyte telomere length (LTL). We further aimed
      to investigate whether this relationship is modified by obesity status.A total of
      2133 participants were recruited from the Korean Genome and Epidemiology Study.
      LTL was measured using the real-time quantitative polymerase chain reaction
      methodology. The FTO rs9939609 polymorphism was genotyped using DNA samples
      collected at baseline.The proportions of the TT, TA, and AA genotypes were 76.7%,
      21.5%, and 1.8%, respectively, and obese subjects comprised 44.5% of the total
      subjects. Among the 1184 nonobese subjects, body mass index, waist circumference,
      and visceral fat area were higher in subjects with the FTO risk allele than in
      noncarriers. In contrast, only high-sensitive C-reactive protein level was
      associated with the FTO risk allele in the obese subjects. LTL was significantly
      shorter in carriers of the FTO risk allele compared with noncarriers after
      controlling for several confounding factors (P < .01). Of particular note, this
      significant association between the FTO risk allele and LTL appeared only in
      nonobese subjects (P = .03). Multivariate linear regression analyses identified
      older age, low high-density lipoprotein cholesterol level, and the presence of
      the FTO risk allele as independent risk factors affecting LTL. This finding was
      evident only in nonobese subjects.The FTO rs9939609 polymorphism is an
      independent risk factor for obesity and also for biological aging in the nonobese
      population.

PMID- 28746204
TI  - Direct-acting antiviral agent efficacy and safety in renal transplant recipients
      with chronic hepatitis C virus infection: A PRISMA-compliant study.
AB  - BACKGROUND: The efficacy and safety of direct-acting antivirals (DAAs) for
      treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has
      not been determined. METHODS: We searched PubMed, Embase, and the Cochrane
      Central Register of Controlled Trials and assessed the quality of eligible
      studies using the Joanna Briggs Institute scale. DAA efficacy and safety were
      assessed using standard mean difference (SMD) with 95% confidence intervals
      (95%CIs). RESULTS: Six studies (360 RTRs) were included. Two hundred thirty six
      RTRs (98.3%) achieved sustained virological response within 12 weeks; HCV
      infection was cleared in 239 RTRs after 24-week treatment. Liver function
      differed significantly pre- and posttreatment (alanine aminotransferase, SMD:
      0.96, 95%CIs: 0.65, 1.26; aspartate aminotransferase, SMD: 0.89, 95%CIs: 0.60,
      1.18); allograft function pre- and posttreatment was not statistically different
      (serum creatinine, SMD: -0.13, 95%CIs: -0.38, 0.12; estimated glomerular
      filtration rate, SMD: 0.20, 95%CIs: -0.11, 0.51). General symptoms (fatigue
      nausea dizziness or headache) were the most common adverse events (AEs) (39.3%).
      Severe AEs, that is, anemia, portal vein thrombosis, and streptococcus
      bacteraemia and pneumonia, were present in 1.1%, 0.6%, and 1.1% of RTRs,
      respectively. CONCLUSION: Our findings suggest that DAAs are highly efficacious
      and safe for treating HCV-infected RTRs and without significant AE.

PMID- 28746205
TI  - Nomograms predicting disease-specific regional recurrence and distant recurrence
      of papillary thyroid carcinoma following partial or total thyroidectomy.
AB  - The study aimed to establish effective nomograms for prediction of tumor regional
      recurrence and distant recurrence of papillary thyroid carcinoma (PTC) patients
      after partial or total thyroidectomy.These nomograms were based on a
      retrospective study on 1034 patients who underwent partial or total thyroidectomy
      for PTC. The predictive accuracy and discriminative ability of the nomograms were
      evaluated by the concordance index (C-index) and calibration curve. In addition,
      a validation cohort was included at the same institution.Multivariate analysis
      demonstrated that family history, maximal tumor diameter, capsular invasion, and
      lymph node staging were independent risk factors for regional recurrence-free
      survival; and family history, histological variants, capsular invasion,
      perineuronal invasion, and vascular invasion were independent risk factors for
      distant recurrence-free survival. They were selected into the 2 nomograms,
      respectively, and the C-index for regional recurrence-free survival and distant
      recurrence-free survival prediction were 0.72 and 0.83, respectively. In the
      validation cohort, the 2 nomograms displayed a C-index of 0.72 and 0.89,
      respectively.The nomograms developed in this study demonstrated their
      discrimination capability for predicting 3 and 5-year regional recurrence and
      distant recurrence after partial or total thyroidectomy, and can be used to
      identify high-risk patients.

PMID- 28746206
TI  - Association between relative liver enhancement on gadoxetic acid enhanced
      magnetic resonance images and histologic grade of hepatocellular carcinoma.
AB  - We evaluated the association between histologic grade of hepatocellular carcinoma
      (HCC) and degree of HCC enhancement on Gd-EOB-DTPA (Gadoxetic acid, Primovist)
      enhanced magnetic resonance images (MRI) in HCC patients.A total of 121 patients
      who underwent curative surgical resection for HCC at our institution between
      January 2012 and March 2015 were retrospectively analyzed. Gadoxetic acid
      enhanced MRI was performed in all patients before surgery. Signal intensities of
      HCC and peri-HCC areas were measured using regions of interest. Relative
      intensity ratios of HCC lesions versus the surrounding non-HCC areas on
      unenhanced images (precontrast ratio) and on hepatobiliary phase images
      (postcontrast ratio) were calculated. Relative liver enhancement (RLE) ratios
      (post-contrast ratio/pre-contrast ratio) were also calculated. The Edmondson
      Steiner (E-S) grading system was used to histologically grade HCC.E-S grades I,
      II, III, and IV were observed in 2 (1.7%), 14 (11.6%), 54 (44.6%), and 51 (42.1%)
      of the patients, respectively. For E-S grades I/II (n = 16), III (n = 54), and IV
      (n = 51), mean RLE (%) were 85.5, 84.9, and 71.2, respectively (P = .01), and for
      E-S grades I-III (n = 70) and IV (n = 51), mean RLE (%) were 85.1 and 71.2,
      respectively (P < .01). Barcelona Clinic Liver Cancer (BCLC) stage A (vs 0) (odds
      ratio 4.38, P = .03) and mean RLE (odds ratio 0.05, P < .01) were found to
      predict E-S grade IV.E-S grade IV was associated with a low level mean RLE in the
      gadoxetic acid enhanced MR images of HCC patients.

PMID- 28746207
TI  - Integrating nested PCR with high-throughput sequencing to characterize mutations
      of HBV genome in low viral load samples.
AB  - Due to the low viral load of hepatitis B virus (HBV) in plasma samples,
      conventional techniques have limitations to the detection of antiviral resistance
      mutations. To solve the problem, we developed a fast, highly sensitive, and
      accurate method to sequence the HBV whole-genome sequencing in plasma samples
      which had various viral loads from very low to high.Twenty-one plasma samples
      were collected from patients who were carriers of HBV from the Hangzhou First
      People's Hospital. Two pairs of conserved, overlapping, nested primers were used
      to amplify and sequence the whole HBV genome in 8 plasma samples with different
      viral loads. High-throughput sequencing was performed on Illumina MiSeq platform.
      Concomitantly, 3 samples were directly sequenced without PCR amplification. We
      compared amplicon-sequencing with direct sequencing to develop a method for
      amplifying and characterizing the whole genome of HBV.HBV genome was amplified
      from all samples and verified by Sanger sequencing, regardless of the viral
      loads. Sequencing results revealed that only a few reads were mapped to the HBV
      genome following direct sequencing, while the amplicon-sequencing reads had a
      good coverage and depth. We identified 50 intrahost single nucleotide variations
      (iSNVs), 14 of which were low frequency mutations. Interestingly, iSNVs were more
      common in low viral load samples than in high viral load samples, and mutations
      in the reverse transcriptase (RT) region were most prevalent.We conclude that
      amplicon-sequencing is not only a practical method to detect HBV infection with a
      high sensitivity and accuracy but also enables to detect mutations in the HBV
      genome in low viral load samples from HBV-infected patients. Thus, our findings
      provide a new diagnosis method of HBV infection, which is capable of detection of
      low frequent mutations in low viral load samples.

PMID- 28746208
TI  - Myopathy in hyperthyroidism as a consequence of rapid reduction of thyroid
      hormone: A case report.
AB  - RATIONALE: Myalgia and elevated creatine kinase (CK) are occasionally observed
      during the treatment of hyperthyroid patients. Relative hypothyroidism resulted
      from rapid thyroid hormone reduction had been promoted as a plausible cause of
      these myopathic changes, however rarely reported. PATIENT CONCERNS: We hereby
      presented a 20-year-old female with Grave's disease, who developed myopathy and
      elevated CK during rapid correction of thyroid hormone. DIAGNOSES: Relative
      hypothyroidism-induced myopathy. INTERVENTIONS: Antithyroid drug (ATD) dosage was
      reduced without levothyroxine replacement. OUTCOMES: The muscular symptoms were
      recovered with CK level returned to normal after adoption of the euthyroid
      status. LESSONS: Differentiation of relative hypothyroidism from other causes of
      myopathy, especially with the effect of ATD, is important for clinical practice,
      although difficult in many cases.

PMID- 28746209
TI  - Pedicled buccal fat pad for the augmentation of facial depression deformity: A
      case report.
AB  - RATIONALE: Tissue augmentation of facial depression deformities can be achieved
      by volume replacement with autologous fat injection, dermal filler injection,
      etc. Here, we report a case of tissue augmentation of a facial depression
      deformity using a pedicled buccal fat pad (BFP). PATIENT CONCERNS: A 64-year-old
      woman was referred with a chief complaint of facial depression deformity.
      DIAGNOSES: Her molars had been removed at another hospital 12 years prior to this
      referral, and the patient suffered from a left cheek depression deformity as a
      sequela of a postextraction infection. INTERVENTIONS: An incision was made in the
      left gingivobuccal sulcus under local anesthesia, and BFP was carefully excised
      from its normal location. The subcutaneous scar tissue was dissected, and a
      pocket was created via the same mucosal incision. BFP was then pushed into the
      pocket. OUTCOMES: The depression deformity immediately disappeared
      postoperatively. The transplanted BFP remained unabsorbed and soft 43 months
      postoperatively. The patient did not have any complications. LESSONS: This novel
      procedure has 2 advantages. First, the pedicled BFP is a vascularized tissue and
      is not absorbed postoperatively; control of contour is easy, and only 1 treatment
      session is required. Complications associated with fat necrosis can be avoided.
      Second, only a single intraoral incision is required; the risk of donor-site
      morbidity is very low, and scar formation does not occur on exposed skin. Third,
      this procedure can be performed without special instruments and equipment. The
      main disadvantages are limited rotation arc and volume of pedicled BFP. Despite
      its limited application, this procedure is simple and useful, with low
      invasiveness.

PMID- 28746210
TI  - Anticancer effect of Saussurea lappa extract via dual control of apoptosis and
      autophagy in prostate cancer cells.
AB  - To demonstrate the mechanisms of the curative effect of Saussurea lappa ethanol
      extract (SLE) against prostate cancer, we evaluated the effect of SLE on the
      induction of apoptosis and autophagy and investigated whether SLE-induced
      autophagy exerts a pro-survival or pro-apoptotic effect in lymph node carcinoma
      of the prostate (LNCaP) prostate cancer cells. SLE was prepared using 100%
      ethanol and added to LNCaP cells for 24 hours. Cell viability was determined by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell
      apoptosis was evaluated by Tali assay. The expression of apoptosis-related mRNA
      and proteins was analyzed by quantitative real-time RT-PCR and western blotting.
      SLE treatment decreased the viability of LNCaP cells and increased Bax expression
      while suppressing the expression of pro-caspases-8/9/3, PARP, Bid, and Bcl-2,
      thereby inducing apoptosis in LNCaP cells. Cell proliferation related proteins,
      including p-Akt, androgen receptor, and prostate-specific antigen, were
      suppressed by SLE treatment. SLE also induced autophagy in LNCaP cells, and
      inhibition of autophagy enhanced the apoptosis induced by SLE treatment. These
      results suggest that SLE exerts anticancer effects through the induction of both
      cellular apoptosis and autophagy, and apoptotic cell death can be facilitated by
      blocking autophagy in SLE-treated LNCaP cells. Therefore, SLE might be a
      potential anticancer agent for the treatment of prostate cancer.

PMID- 28746211
TI  - Epidermal growth factor promotes proliferation and maintains multipotency of
      continuous cultured adipose stem cells via activating STAT signal pathway in
      vitro.
AB  - This study aimed to investigate the effects of epidermal growth factor (EGF) on
      the proliferation and differentiation of adipose stem cells (ASC) during the
      repeated passaging and probe the underlying signal pathway. Results showed that
      the Ki67 positive rate remained at a high level, the number of ASCs in G0/G1
      phase reduced significantly, but ASCs in G2/M phase and S phase increased
      markedly in ASCs treated with EGF when compared with ASCs without EGF treatment,
      indicating that EGF made more ASCs in proliferation phase. The adipogenic
      capability of ASCs without EGF was compromised when compared with that of ASCs
      after EGF treatment, although significant difference was not observed. The
      osteogenic and chondrogenic potencies increased significantly in ASC with EGF
      treatment indicating EGF could maintain differentiative capacity of ASCs. Gene
      Set Enrichment Analysis showed EGF upregulated the expression of molecules in the
      epithelial mesenchymal transition and G2/M checkpoint signal pathways. GeneMANIA
      database analysis indicated the network interaction between EGF and STAT. EGF
      receptor (EGFR) inhibitor and STAT3 inhibitor were independently used to validate
      the role of both pathways in these effects. After inhibition of EGFR or STAT3,
      the proliferation of ASCs was significantly inhibited, and Western blotting
      showed EGF was able to markedly increase the expression of EGFR and STAT3. These
      findings suggest EGF not only promotes the proliferation of ASCs and delays their
      senescence, but also maintains the differentiation potency of ASCs, which are
      related to the EGF-induced activation of STAT signal pathway.

PMID- 28746212
TI  - Intermediate-stage hepatocellular carcinoma patients with a high HBV-DNA load may
      benefit from postoperative anti-hepatitis B virus therapy.
AB  - Liver resection may be beneficial in intermediate-stage hepatocellular carcinoma
      (HCC), though the benefit of postoperative anti-hepatitis B virus (HBV) therapy
      in these patients remains unclear. In this study, we sought to evaluate the
      efficacy of postoperative anti-HBV for intermediate-stage HCC patients who
      underwent radical liver resection.According to inclusion and exclusion criteria,
      this study enrolled 202 HCC patients who underwent liver resection and had a high
      HBV-DNA load. The patients were divided into 2 groups on the basis of
      postoperative anti-HBV therapy: group A included patients undergoing
      postoperative anti-HBV therapy, whereas group B patients did not receive any
      postoperative anti-HBV therapy. Factors including baseline demographics, tumor
      characteristics, overall long-term survival, tumor-free survival, and tumor
      recurrence rate were compared between the 2 groups. Moreover, univariate and
      multivariate analyses were used to identify risk factors of HCC
      recurrence.Baseline demographics and tumor characteristics were comparable
      between the groups. The 1-, 3-, and 5-year overall survival rates in group A were
      91.3%, 80.9%, and 66.1%, respectively, values that were significantly increased
      compared with group B (91.7%, 60.7%, and 52.4%, respectively, P = .019). Group A
      patients also exhibited enhanced 1-, 3-, and 5-year tumor-free survival compared
      with group B patients (87.0%, 67.0%, and 62.6%, respectively, in group A; 82.1%,
      50.0%, and 42.9% in group B, P = .002). In addition, the tumor recurrence rate in
      group B was significantly increased compared with group A (P < .01). Univariate
      and multivariate analyses indicated lack of postoperative anti-HBV therapy
      [hazard ratio (HR) = 0.882; 95% confidence interval (CI), 0.712-0.938; P = .042]
      to be a predictor of tumor recurrence.For intermediate-stage [Barcelona Clinic
      Liver Cancer (BCLC) stage B] HCC with a high HBV-DNA load, postoperative anti-HBV
      therapy after curative resection should be routine adjuvant therapy.

PMID- 28746213
TI  - Is combined topical and intravenous tranexamic acid superior to single use of
      tranexamic acid in total joint arthroplasty?: A meta-analysis from randomized
      controlled trials.
AB  - BACKGROUND: To compare the efficacy and safety of the combined application of
      both intravenous and topical tranexamic acid (TXA) versus the single use of
      either application in patients with total knee and hip arthroplasty (TKA and
      THA). METHODS: Potentially relevant studies were identified from electronic
      databases including Medline, PubMed, Embase, ScienceDirect, and the Cochrane
      Library. Randomized control trials (RCTs) of patients prepared for total joint
      arthroplasty that compared combined TXA with placebo were retrieved. The primary
      endpoint was hemoglobin decline or postoperative hemoglobin level, blood loss,
      drainage volume, transfusion requirements. The secondary outcomes were length of
      stay (LOS), and operation time as well as surgery-related adverse effects, such
      as wound infection, deep vein thrombosis (DVT), and pulmonary embolism (PE).
      After testing for publication bias and heterogeneity between studies, data were
      aggregated for random-effects models when necessary. RESULTS: Five RCTs that
      included 604 patients met the inclusion criteria. The present meta-analysis
      indicated significant differences existed in the total blood loss (mean
      difference [MD] = -134.65, 95% CI: -191.66 to -77.64, P < .0001), postoperative
      hemoglobin level (MD = 0.74, 95% CI: 0.39-1.10, P < .0001), drainage volume (MD =
      -47.44, 95% CI: -64.55 to -30.33, P < .00001), and transfusion rate (risk
      difference [RD] = -0.06, 95% CI: -0.10 to -0.02, P = .006) between groups.
      CONCLUSION: Combined administration of TXA in TKA and THA was associated with
      significantly reduced total blood loss, postoperative hemoglobin decline,
      drainage volume, and transfusion requirements. Well-designed, high-quality RCTs
      with long-term follow-up are still required.

PMID- 28746214
TI  - External validation of non-invasive prediction models for identifying
      ultrasonography-diagnosed fatty liver disease in a Chinese population.
AB  - Several prediction models for fatty liver disease (FLD) are available with
      limited externally validation and less comprehensive evaluation. The aim was to
      perform external validation and direct comparison of 4 prediction models (the
      Fatty Liver Index, the Hepatic Steatosis Index, the ZJU index, and the Framingham
      Steatosis Index) for FLD both in the overall population and the obese
      subpopulation.This cross-sectional study included 4247 subjects aged 20 to 65
      years recruited from the north of Shanxi Province in China. Anthropometric and
      biochemical features were collected using standard protocols. FLD was diagnosed
      by liver ultrasonography. We assessed all models in terms of discrimination,
      calibration, and decision curve analysis.The original models performed well in
      terms of discrimination for the overall population, with the area under the
      receiver operating characteristic curves (AUCs) around 0.85, while AUCs for obese
      individuals were around 0.68. Nevertheless, the predicted risks did not match
      well with the observed risks both in the overall population and the obese
      subpopulation. The FLI 2006 was 1 of the 2 best models in terms of discrimination
      (AUCs were 0.87 and 0.72 for the overall population and the obese subgroup,
      respectively) and had the best performance in terms of calibration, and attained
      the highest net benefit.The FLI 2006 is overall the best tool to identify high
      risk individuals and has great clinical utility. Nonetheless, it does not perform
      well enough to quantify the actual risk of FLD, which need to be (re)calibrated
      for clinical use.

PMID- 28746215
TI  - S-1 monotherapy versus S-1 combination therapy in gemcitabine-refractory advanced
      pancreatic cancer: A meta-analysis (PRISMA) of randomized control trials.
AB  - BACKGROUND: Pancreatic cancer (PC) is one of the most lethal digestive system
      tumors. Most new cases are diagnosed based on metastasis or local aggression and
      are known as "advanced PC." Recently, studies investigating S-1 have indicated
      that it has a better clinical curative effect on PC. We conducted a meta-analysis
      to evaluate the efficacy and safety of S-1 monotherapy compared with S-1
      combination regimens in patients with gemcitabine (GEM)-refractory PC. METHODS:
      Trials published between 1978 and 2016 were identified by an electronic search of
      public databases (Medline, Embase, and the Cochrane Library). All prospective
      studies were independently identified by 2 authors for inclusion. The response
      rate (RR), progression-free and overall survival (PFS and OS, respectively), and
      the primary toxicities were extracted for the meta-analysis. RESULTS: Four
      randomized controlled trials consisting of 623 patients were included in the
      analysis, among which 315 patients underwent S-1 monotherapy and 308 patients
      underwent S-1 combination therapy. The pooled data showed a significantly higher
      response rate and longer PFS in the S-1 combination group than in the S-1
      monotherapy group (RR, 1.75; 95% confidence interval [CI], 1.19-2.57; P = .005
      and hazard ration [HR], 0.75; 95% CI, 0.62-0.91; P = .005). There were no
      significant differences in OS or adverse events. CONCLUSIONS: Compared with the S
      1 monotherapy group, the S-1 combination group had a higher response rate and
      longer PFS. Both groups had few adverse events, which were balanced between the
      groups. The subgroup analysis suggested that S-1 combination regimens with
      leucovorin or irinotecan (CPT-11) provided promising efficacy. These promising
      combination regimens should be considered for patients with advanced PC who
      choose S-1 as their second-line therapy.

PMID- 28746216
TI  - The impact of host's genetic susceptibility on Helicobacter pylori infection in
      children.
AB  - The aim of our study was to investigate the impact of interleukin (IL)-6 190C/T,
      IL-6 174G/C, IL-6 572G/C, tumor necrosis factor-alpha (TNF-alpha) 308G/A, and
      angiotensin-converting enzyme (ACE) I/D gene polymorphisms on Helicobacter pylori
      (H. pylori) infection in children.A cross-sectional study was performed on 126
      children (57 children with H. pylori infection and 69 children without H. pylori
      infection) aged between 3 and 18 years presenting to a Pediatrics Tertiary
      Hospital from Romania. Children were assessed clinically, endoscopically,
      histopathologically, and genetically.In our study, we found that the presence of
      the CT and CT+TT genotypes of IL-6 190C/T (P < .002 and P = .04), allele G of IL
      6 572 G/C polymorphism (P = .01), genotypes GA and AA of TNF-alpha 308 G/A
      polymorphism (P = .04, P = .01), and genotype II of ACE I/D polymorphism (P =
      .02) were associated with H. pylori infection, while the CC genotype of IL-6
      174G/C polymorphism was scarcely encountered in children with H. pylori infection
      [P = .02, odds ratio (OR) = 0.06; 95% confidence interval (95% CI): 0.003-0.128].
      Taking under consideration the 4 variant genotypes (IL-6 572G/C, IL-6 190C/T, TNF
      alpha 308G/A, and ACE I/D), we noticed a 2 times higher incidence of H. pylori
      infection (OR = 6.34; 95% CI: 2.15-25.8).We may consider that the IL-6 190C/T, IL
      6 174G/C, IL-6 572G/C, TNF-alpha 308G/A, and ACE I/D gene polymorphisms may
      increase the children's susceptibility for acquiring H. pylori infection;
      therefore, they may contribute to the pathogenesis of H. pylori gastritis.

PMID- 28746217
TI  - 18F-fluoro-deoxy-glucose positron emission tomography combined with computed
      tomography can reliably rule-out infection and cancer in patients with anti
      neutrophil cytoplasmic antibody-associated vasculitis suspected of disease
      relapse.
AB  - Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a
      group of autoimmune diseases characterized by systemic inflammation in small- to
      medium-sized blood vessels. Although immunosuppressive therapy has greatly
      improved the prognosis for these patients, there are still significant
      comorbidities, such as cancer and infection, associated with AAV. These
      comorbidities are often indistinguishable from an underlying AAV disease relapse,
      and create a clinical conundrum, as these conditions are normally
      contraindications for immunosuppressive treatment. Thus, it is important to be
      able to rule out these comorbidities before initiation of immunosuppressive
      treatment. We examined F-fluoro-deoxy-glucose positron emission tomography
      combined with computed tomography (FDG-PET/CT)'s value in ruling out cancer or
      infection in patients with AAV.Data were obtained retrospectively for a
      clinically based cohort of AAV patients who underwent FDG-PET/CT during 2009 to
      2014 owing to a suspicion of cancer, infection, or both cancer and infection
      indistinguishable from disease relapse. FDG-PET/CT conclusions were compared to
      the final diagnoses after follow-up analysis (mean 43 months).A total of 19
      patients were included who underwent a total of 26 scans. The results of FDG
      PET/CT outcome compared to final diagnosis were: 9 true positives, 3 false
      positives, 13 true negatives, and 1 false negative. The diagnostic probabilities
      for FDG-PET/CT with respect to overall comorbidity (i.e., cancer or infection)
      were: sensitivity 90% ( 95% confidence interval [CI] 60%-98%), specificity 81% (
      95% CI 57%-93%), positive predictive value 75% (95% CI 47%-91%), negative
      predictive value 93% (95% CI 68%-99%), and accuracy 84% (95% CI 66%-94%).FDG
      PET/CT had a high negative predictive value and ruled out the comorbidities
      correctly in all but one case of urinary tract infection, a well-known
      limitation. Our study showed FGD-PET/CT's promise as an effective tool for ruling
      out cancer or infection in patients with AAV albeit in a limited population.

PMID- 28746218
TI  - Localized nasopharyngeal amyloidosis mimicking malignancy: A case report.
AB  - RATIONALE: Nasopharyngeal amyloidosis is a benign, slowly progressive disease
      that is characterized by extracellular eosinophilic deposition. PATIENT CONCERNS:
      We report a rare case of localized nasopharyngeal amyloidosis. DIAGNOSES: The
      initial chief complaint of this patient was frequent epistaxis and right aural
      fullness. The initial diagnosis was nasopharyngeal tumor. INTERVENTIONS: There is
      no universally effective medical treatment for nasopharyngeal amyloidosis but
      surgery can be an option. We performed careful observation with regular follow-up
      by nasopharyngoscopy and radiologic study. OUTCOMES: The patient reported no
      further complaints at 1-year follow-up and the lesion from nasopharyngeal
      amyloidosis was still present. LESSONS: Although it is rare, nasopharyngeal
      amyloidosis should be considered in the differential diagnosis of epistaxis,
      nasal obstruction, and otitis media with effusion, which are the main symptoms of
      nasopharyngeal carcinoma. In the absence of systemic disease, localized
      nasopharyngeal amyloidosis may be treated conservatively.

PMID- 28746219
TI  - Clinical outcomes of medial collateral ligament injury in total knee
      arthroplasty.
AB  - : Intraoperative injury to the medial collateral ligament (MCL) during total knee
      arthroplasty (TKA) is a rare but severe complication. The main treatment methods
      are primary repair and revision with a more constrained implant; however, the
      clinical outcomes of primary reconstruction without a constrained implant have
      rarely been reported.A retrospective study was performed to evaluate the
      prevalence of iatrogenic injury to the MCL during primary TKA, and to report the
      clinical outcomes of MCL reconstruction without the use of a constrained device.A
      total of 1749 patients (2054 knees) underwent primary TKA between 2007 and 2013
      and were retrospectively evaluated. Seventeen patients (0.83%) experienced an MCL
      injury intraoperatively, and the remaining 1732 patients (2037 knees) were
      considered as the controls. We attempted to reconstruct the MCL with an
      unconstrained prosthesis in all patients. The Knee Society Score (KSS) was used
      to evaluate knee function after an average 51-month follow-up (range, 36-72
      months).No patients were lost during the follow-up period. In the MCL injury
      group, the mean KSS was 84.7 for function and 87.7 for pain, while the scores
      were 87.9 and 90.6, respectively, in the control group. No patient treated with
      MCL reconstruction without increased prosthetic constraint experienced knee
      instability requiring revision.MCL reconstruction without a constrained implant
      achieved excellent results for MCL injury during TKA. LEVEL OF EVIDENCE: Level
      IV, therapeutic study.

PMID- 28746220
TI  - Copy number variations of neurotrophic tyrosine receptor kinase 3 (NTRK3) may
      predict prognosis of ovarian cancer.
AB  - Platinum resistance is a critical barrier for clinicians to improve the survival
      of ovarian cancer. Our study evaluated the correlation between copy number
      variations (CNVs) of neurotrophic tyrosine receptor kinase 3 (NTRK3) and the
      prognosis of ovarian cancer, which might predict platinum resistance in ovarian
      cancer patients.Array comparative genomic hybridization (CGH) was used to test
      gene backgrounds between platinum-sensitive and platinum-resistant relapsed
      populations and CNVs of NTRK3 were indicated by cluster analysis. Fluorescence in
      situ hybridization (FISH) was adopted in 41 cases for further verification, which
      confirmed the results of array CGH. Spearman's rank correlation analysis and chi
      test were used to evaluate the accuracy of CNVs of NTRK3 which predicted platinum
      sensitive or platinum-resistant recurrence.We detected CNVs of NTRK3 between 2
      groups by array CGH, and amplification of NTRK3 was confirmed by FISH in the
      platinum-sensitive recurrence group with enlarged samples. The test concordance
      of 2 methods was 78.6%. Among 41 cases with satisfied FISH results, the median
      time to recurrence (TTR) of patients with amplified and nonamplified NTRK3 were
      respectively 18 and 5 months (P <.01). The cut-off value of TTR to differentiate
      platinum-sensitive or platinum-resistant recurrence was 6 months in accordance
      with clinical practice. According to the above standard, 15 cases with NTRK3
      amplification were platinum-sensitive and 12 cases without NTRK3 amplification
      were platinum-resistant recurrences which demonstrated that the accuracy of NTRK3
      amplification/nonamplification to predict recurrent types was 65.9% (27/41).CNVs
      of NTRK3 were associated with platinum-sensitive and platinum-resistant
      recurrences. Amplification of NTRK3 perfectly predicted platinum-sensitive
      relapse of ovarian cancer.

PMID- 28746221
TI  - Diagnosis and treatment of hidden lesions in "mild" cervical spondylotic
      myelopathy patients with apparent symptoms.
AB  - Patients with apparent symptoms of cervical spondylotic myelopathy (CSM) may only
      show a mild compressive lesion in ordinary magnetic resonance imaging (MRI). The
      aim of this study was to investigate the characteristics of CSM patients with
      "hidden" lesions on kinetic MRI and to determine an effective treatment.Thirty
      one patients with obvious spinal cord compression only on kinetic MRI were
      included in our study. A variety of parameters were calculated from MRI of the
      cervical spine at different postures. The anterior cervical decompression and
      fusion (ACDF) procedure were used for treatment of CSM. To evaluate the effect of
      surgery, a further 31 age- and gender-matched ordinary CSM patients that received
      ACDF procedures were enrolled as the control group.The diameter of the cervical
      cord at the narrowest level in extension was significantly lower than that in the
      neutral posture (P < .01). The percentage of spinal cord compression was 34.6%.
      The diameter of the cervical canal at the narrowest level in the extension
      posture was significantly lower than that in the neutral posture (P < .01). The
      percentage of cervical canal stenosis was 43.6%. The anteroposterior diameter of
      the cervical canal in the case group was significantly lower than that in the
      control group (P < .01). However, the recovery rate of the Japanese Orthopaedic
      Association score at final follow-up was comparable between the case group and
      the control group (P = .53).Kinetic MRI is useful for the diagnosis of CSM with
      hidden lesions. ACDF is an effective procedure for treatment of CSM.

PMID- 28746222
TI  - The use of tenoxicam to prevent symptoms of discomfort induced by vagotonia
      during uterus manipulation in cesarean sections.
AB  - PURPOSE: Symptoms such as nausea, vomiting, tightness of the chest, bradycardia,
      and shoulder or abdominal discomfort, caused by vagotonia occurring during uterus
      manipulation, have concerned healthcare professionals for some time. Patients
      sometimes report these symptoms when undergoing spinal anesthesia for cesarean
      sections (CSs). We designed a prospective, double-blind study to investigate the
      effectiveness of tenoxicam in preventing these symptoms of discomfort. METHODS: A
      total of 105 American Society of Anesthesiologists (ASA) class I-II nulliparous
      pregnant women, who were scheduled for a CS, were enrolled into this prospective,
      double-blind study. Spinal anesthesia was conducted to reach a peak dermatome
      level of no more than T3. The 100 patients were randomly divided into 2 groups
      having completed study course: Group T (N = 50) received a 20 mg dose of
      tenoxicam in 5 mL of normal saline (NS) immediately after skin incision and Group
      N (N = 50) only received 5 mL NS. The incidence and severity of the symptoms
      experienced by the patients were recorded by a nurse anesthetist who was blinded
      to the injection regimen the patients were receiving. A chi-square test was used
      for statistical analysis t test and P < .05 was defined as significant. RESULTS:
      The incidence and degree of severity of nausea and vomiting were same in both the
      groups. The incidence and degree of severity of bradycardia, nausea, vomiting,
      tightness of the chest, shoulder discomfort, and abdominal discomfort were lower
      in Group T than in Group N. CONCLUSION: Tenoxicam might theoretically block the
      parasympathetic vagus pathway and decrease the visceral pain or visceral-specific
      symptoms, alleviating the symptoms caused by vagotonia. However, the prophylactic
      effect of tenoxicam in reducing the incidence and severity of nausea and vomiting
      was not statistically significant. This could be because nausea and vomiting are
      not solely caused by vagotonia, but also by other mechanisms.

PMID- 28746223
TI  - Decreasing incidence and mortality among hospitalized patients suffering a
      ventilator-associated pneumonia: Analysis of the Spanish national hospital
      discharge database from 2010 to 2014.
AB  - The aim of this study was to describe trends in the incidence and outcomes of
      ventilator-associated pneumonia (VAP) among hospitalized patients in Spain (2010
      2014).This is a retrospective study using the Spanish national hospital discharge
      database from year 2010 to 2014. We selected all hospital admissions that had an
      ICD-9-CM code: 997.31 for VAP in any diagnosis position. We analyzed incidence,
      sociodemographic and clinical characteristics, procedures, pathogen isolations,
      and hospital outcomes.We identified 9336 admissions with patients suffering a
      VAP. Incidence rates of VAP decreased significantly over time (from 41.7
      cases/100,000 inhabitants in 2010 to 40.55 in 2014). The mean Charlson
      comorbidity index (CCI) was 1.08 +/- 0.98 and it did not change significantly
      during the study period. The most frequent causative agent was Pseudomonas and
      there were not significant differences in the isolation of this microorganism
      over time. Time trend analyses showed a significant decrease in in-hospital
      mortality (IHM), from 35.74% in 2010 to 32.81% in 2014. Factor associated with
      higher IHM included male sex, older age, higher CCI, vein or artery occlusion,
      pulmonary disease, cancer, undergone surgery, emergency room admission, and
      readmission.This study shows that the incidence of VAP among hospitalized
      patients has decreased in Spain from 2010 to 2014. The IHM has also decreased
      over the study period. Further investigations are needed to improve the
      prevention and control of VAP.

PMID- 28746224
TI  - Alveolar recruitment maneuver attenuates extravascular lung water in acute
      respiratory distress syndrome.
AB  - BACKGROUND: The alveolar recruitment maneuver (RM) has been reported to improve
      oxygenation in acute respiratory distress syndrome (ARDS) and may be related to
      reduced extravascular lung water (EVLW) in animals. This study was designed to
      investigate the effects of RM on EVLW in patients with ARDS. METHODS: An open
      label, prospective, randomized controlled trial including patients with ARDS was
      conducted in hospitals in North Taiwan between 2010 and 2016. The patients were
      divided into 2 groups (with and without RM). The primary endpoint was the
      comparison of the EVLW index between the 2 groups. RESULTS: Twenty-four patients
      with ARDS on mechanical ventilator support were randomized to receive ventilator
      treatment with RM (RM group, n = 12) or without RM (non-RM group, n = 12).
      Baseline demographic characteristics were similar between the 2 groups. After
      recruitment, the day 3 extravascular lung water index (EVLWI) (25.3 +/- 9.3 vs
      15.5 +/- 7.3 mL/kg, P = .008) and the arterial oxygen tension/fractional inspired
      oxygen ratio (PaO2/FiO2) (132.3 +/- 43.5 vs 185.6 +/- 38.8 mL/kg, P = .003) both
      improved over that of day 1. However, both EVLWI and PaO2/FiO2 did not
      significantly change from day 1 to 3 in the non-RM group. CONCLUSION: RM is a
      feasible method for improving oxygenation and the EVLW index in patients with
      ARDS, as well as for decreasing ventilator days and intensive care unit stay
      duration.

PMID- 28746225
TI  - Ulcerative colitis with acute pleurisy: A case report and review of the
      literature.
AB  - RATIONALE: Inflammatory bowel diseases (IBD), including ulcerative colitis (UC)
      and Crohn's disease, are associated with a large number of extraintestinal
      manifestations. Pulmonary manifestations are infrequently seen in patients with
      IBD. Moreover, serositis including pleural and pericardial manifestations in UC
      is rare. PATIENT CONCERNS: We report a case of UC with acute pleurisy in a 43
      year-old man; review literature; and discuss the diagnosis, differential
      diagnosis, and treatment. DIAGNOSES: Active duodenal ulcer was found using
      gastroscopy. Multiple ulcers in segmented pattern were noticed in the left hemi
      colon using colonoscopy. An UC in active stage was confirmed subsequently by
      histology. INTERVENTION: The patient was treated with bifidobacterium
      tetravaccine tablets, oral mesalazine and mesalazine enemas. The omeprazole and
      mucosal protective agents were given to treat the duodenal ulcer. OUTCOMES: As
      follow-up, the therapy including oral mesalazine and infliximab regularly was
      continued and the patient condition was stabilized. MAIN LESSON: Pulmonary
      involvement should be considered in patients who develop pleurisy in UC.
      Infliximab is considered the better available treatment for patients presenting
      with pleurisy in UC.

PMID- 28746226
TI  - The use of a dorsal double-wing flap without skin grafts for congenital
      syndactyly treatment: A STROBE compliant study.
AB  - Numerous techniques have been developed that use various flaps to treat
      syndactyly. Skin grafts have often been used to cover remaining surgical defects.
      The long-term aim of surgery is to find new methods of separating the digits
      without using skin grafts. This paper describes a new surgical technique for the
      correction of simple, incomplete, and complete syndactyly. The technique consists
      of a dorsal double-wing flap to cover the newly created web space and zigzag
      incisions in the fingers, thus avoiding the use of skin grafts in this space.
      Overall, 35 web spaces in 24 patients were treated using this technique. Patient
      follow-up ranged from 6 months to nearly 5 years. There were no complications
      such as hematoma, infection or flap necrosis, and no fingers needed skin grafts
      after separation. The average operative time for each web space was approximately
      45 minutes. Ninety-seven percent of patients treated with the dorsal double-wing
      flap procedure achieved good function, and superior cosmetic results following a
      single surgery. The technique is simple, rapid, safe, and easily performed and
      does not require the use of skin grafts.

PMID- 28746227
TI  - Diagnostic yield of stool culture and predictive factors for positive culture in
      patients with diarrheal illness.
AB  - We aimed to investigate the diagnostic yield of stool cultures and identify
      predictive factors for positive cultures in patients with diarrheal illness.A
      total of 13,327 patients who underwent stool cultures due to diarrheal illness
      were reviewed. Stool cultures were performed for enteric pathogens, including
      Salmonella, Shigella, Vibrio, Klebsiella oxytoca, and Yersinia. The culture
      positive group was compared with the culture-negative group who were randomly
      selected from culture negative patients.A total of 196 patients (1.47%) were
      diagnosed with positive stool culture. In 196 culture positive patients,
      Salmonella spp. (75.0%) was detected most commonly, followed by Vibrio (19.4%).
      Univariate analyses showed fever (>37.8 degrees C), vomiting, duration and
      frequency of diarrhea, and high C-reactive protein (CRP) were significantly
      associated with positive stool culture. Multivariate analysis showed fever (odds
      ratio [OR], 2.33; 95% confidence interval [CI], 1.25-4.35; P = .008), >=5/day of
      diarrhea (OR, 3.52; 95% CI, 1.93-6.44; P < .001) and >50 mg/L of CRP (OR, 2.27;
      95% CI, 1.18-4.36; P = .014) were independent predictors for positive stool
      culture. OR in patients with all 3 factors was 6.55 (95% CI, 2.56-16.75; P <
      .001). Vomiting (OR, 0.32; 95% CI, 0.17-0.57; P < .001) was a negative predictive
      factor.Diagnostic yield of stool culture in patients with diarrheal illness is
      very low. Fever, frequency of diarrhea, and high CRP are predictors for positive
      stool cultures. These findings may lead to more discerning and cost-effective
      utilization of stool culture by clinicians.

PMID- 28746228
TI  - Randomized, noninferiority study between video versus hand ultrasound with wet
      foam dressing materials to simulate B-lines in lung ultrasound: A CONSORT
      compliant article.
AB  - BACKGROUND: This study evaluated the efficacy of a teaching method using
      simulated B-lines of hand ultrasound with a wet foam dressing material. METHODS:
      This prospective, randomized, noninferiority study was conducted on emergency
      medical technician students without any relevant training in ultrasound.
      Following a lecture including simulated (SG) or real video clips (RG) of B-lines,
      a posttest was conducted and a retention test was performed after 2 months. The
      test consisted of questions about B-lines in 40 randomly mixed video clips (20
      simulated and 20 real videos) with 4 answer scores (R-1 [the correct answer score
      for the real video clips] vs S-1 [the correct answer score for the simulated
      video clips] in the posttest, R-2 [the correct answer score for the real video
      clips] vs S-2 [the correct answer score for the simulated video clips] in the
      retention test). RESULTS: A total of 77 and 73 volunteers participated in the
      posttest (RG, 38; SG, 39) and retention test (RG, 36; SG, 37), respectively.
      There was no significant (P > .05) difference in scores of R-1, S-1, R-2, or S-2
      between RG and SG. The mean score differences between RG and SG were -0.6 (95%
      confidence interval [CI]: -1.49 to 0.11) in R-1, -0.1 (95% CI: -1.04 to 0.86) in
      S-1, 0 (95% CI: -1.57 to 1.50) in R-2, and -0.2 (95% CI: -1.52 to 0.25) in S-2.
      The mean differences and 95% CIs for all parameters fell within the
      noninferiority margin of 2 points (10%). CONCLUSION: Simulated B-lines of hand
      ultrasound with a wet foam dressing material were not inferior to real B-lines.
      They were effective for teaching and simulations. TRIAL REGISTRATION: The study
      was registered with the Clinical Trial Registry of Korea:
      https://cris.nih.go.kr/cris/index.jsp (KCT0002144).

PMID- 28746229
TI  - The prognostic value of preoperative inflammation-based prognostic scores and
      nutritional status for overall survival in resected patients with nonmetastatic
      Siewert type II/III adenocarcinoma of esophagogastric junction.
AB  - BACKGROUND: Immune and nutritional status of patients have been reported to
      predict postoperative complications, recurrence, and prognosis of patients with
      cancer. Therefore, this retrospective study aimed to explore the prognostic value
      of preoperative inflammation-based prognostic scores [neutrophil-lymphocyte ratio
      (NLR), platelet-lymphocyte ratio (PLR)] and nutritional status [prognostic
      nutritional index (PNI), body mass index (BMI), hemoglobin, albumin, and
      prealbumin] for overall survival (OS) in adenocarcinoma of esophagogastric
      junction (AEG) patients. METHODS: A total of 355 patients diagnosed with Siewert
      type II/III AEG and underwent surgery between October 2010 and December 2011 were
      followed up until October 2016. Receiver operating characteristic (ROC) curve
      analysis was used to determine the cutoff values of NLR, PLR, and PNI. Kaplan
      Meier curves and Cox regression analyses were used to calculate the OS
      characteristics. RESULTS: The ideal cutoff values for predicting OS were 3.5 for
      NLR, 171 for PLR, and 51.3 for PNI according to the ROC curve. The patients with
      hemoglobin <120 g/L (P = .001), prealbumin <180 mg/L (P = .000), PNI <51.3 (P =
      .010), NLR >3.5 (P = .000), PLR >171 (P = .006), and low BMI group (P = .000) had
      shorter OS. And multivariate survival analysis using the Cox proportional hazards
      model showed that the tumor-node-metastasis stage, BMI, NLR, and prealbumin
      levels were independent risk factors for the OS. CONCLUSION: Our study
      demonstrated that preoperative prealbumin, BMI, and NLR were independent
      prognostic factors of AEG patients.

PMID- 28746230
TI  - TACE plus percutaneous chemotherapy-lipiodol treatment of unresectable
      pedunculated hepatocellular carcinoma.
AB  - Pedunculated hepatocellular carcinoma (P-HCC) is rare type of HCC. The study
      aimed to evaluate the clinical features and outcomes of unresectable P-HCC
      treated with transcatheter arterial chemoembolization (TACE) and percutaneous
      chemotherapeutic agents lipiodol emulsion (CALE) injection. The clinical features
      and outcomes of 25 patients with unresectable P-HCC treated with TACE plus
      percutaneous CALE injection were retrospectively reviewed, and factors associated
      with outcomes were analyzed. Comparison with nonpedunculated unresectable HCC was
      also performed. Patients underwent a median of 4 TACE sessions and received a
      median of 2 percutaneous CALE injections. The 1-, 2-, 3-, and 5-year actuarial
      survival rates were 78.9%, 52.6%, 42.1%, and 12.0%, respectively, for patients
      with P-HCC, and median survival was 27 months (95% confidence interval, 22.6-43.2
      months). Patients with P-HCC had better overall survival than those with
      nonpedunculated HCC (NP-HCC) (P = .002). Vascular invasion and abdominal lymph
      node metastasis were poor prognostic factors for overall survival in patients
      with P-HCC. TACE plus percutaneous CALE injection is a safe and effective
      treatment for unresectable P-HCC. Patients with unresectable P-HCC might have
      better overall survival than those with NP-HCC after TACE plus percutaneous CALE
      injection. However, their prognosis remains poor.

PMID- 28746231
TI  - A comparative study to evaluate the efficacy of EGF, FGF-2, and 0.3% (w/v)
      ofloxacin drops on eardrum regeneration.
AB  - BACKGROUND: Traumatic tympanic membrane perforations (TMPs) tend to spontaneous
      healing, however, large TMPs usually fail to healing. Clinical and experimental
      studies had demonstrated that growth factors accelerated the healing of large
      TMPs. The aim of this study was to compare the effects of growth factors and 0.3%
      (w/v) ofloxacin drops n the healing of human large TMPs. METHODS: A total of 184
      human large traumatic TMPs were randomly assigned to receive epidermal growth
      factor (EGF) treatment, fibroblast growth factor-2 (FGF-2) treatment, 0.3% (w/v)
      ofloxacin drops treatment, and conservative observation (only). RESULTS: A total
      of 180 patients were analyzed in this study at the 6-month follow-up. The closure
      rates of the perforations in the EGF, FGF-2, 0.3% (w/v) ofloxacin drops, and
      conservative observation groups were 91.11%, 93.18%, 95.65%, and 82.22%,
      respectively, the closure rates did not significantly differ among the groups (P
      = .165). Similarly, pairwise comparisons did not reveal any significant between
      group differences (P > .0083). However, the difference of the mean closure time
      was significant among the 4 groups (P < .001), pairwise comparisons showed that
      closure time was significantly longer in the observational group than in the
      other 3 groups (P < .001). Nevertheless, no significant difference in mean
      closure time was evident between any 2 treated groups (P > .0083). The mean
      hearing gain after 6 months was 11.49 +/- 5.88 dB for the EGF group, 10.89 +/-
      5.16 dB for the FGF-2 group, 10.54 +/- 5.56 dB for the ofloxacin group, and 9.29
      +/- 5.36 dB for the observation group. Differences in hearing improvement rates
      among the 4 groups were not statistically significant (P = .283). CONCLUSION:
      Epidermal growth factor, FGF-2, and 0.3% (w/v) ofloxacin drops accelerated the
      closure of large TMPs compared with conservative treatment. Surprisingly, neither
      the closure rate nor closure time differed significantly among the 3 treated
      groups. Further experimental studies to demonstrate whether 0.3% (w/v) ofloxacin
      per se accelerates the healing of TMPs will be interesting in the future.

PMID- 28746232
TI  - The effect of topical thiocolchicoside in preventing and reducing the increase of
      muscle tone, stiffness, and soreness: A real-life study on top-level road
      cyclists during stage competition.
AB  - In professional road cyclists, the majority of overuse injuries affect the lower
      limbs and are mostly represented by contractures or muscle shortening,
      characterized by an increase of tone and stiffness and a variation of elasticity.
      Treatment and prevention of these specific conditions may include physical,
      supplementary, and pharmacologic support. The aim of this real-life study was to
      determine: first, the alterations of tone, stiffness, elasticity, and soreness of
      rectus femoris (RF) and biceps femoris (BF) in top class cyclists engaged in 3
      multistage races, and second, whether any variable in the management of the
      athletes may affect the prevention and/or reduction of such alterations.Twenty
      three professional cyclists competing in 3 international, cycling stage races
      were assessed. Athletes could receive, upon the approval of the medical staff,
      physical, dietary, and/or pharmacological management which could include
      treatments with topical over-the-counter myorelaxants to prevent and/or reduce
      muscle contractures. MyotonPro was used to daily measure tone, stiffness, and
      elasticity in RF and BF in relaxed and contracted state after every stage. In
      parallel, BF and RF soreness was also assessed with a Likert scale.All athletes
      received the same general massage management; none of them received dietary
      supplements; some of the athletes were treated with a topical myorelaxant
      thiocolchicoside (TCC 0.25%) foam 3 times daily. TCC was identified as the only
      variable able to affect these muscle parameters in the cyclists. Tone, stiffness
      (regardless of the state), and soreness significantly increased over time either
      in BF or RF in all athletes. In the group of athletes that used TCC (n = 11;
      TCC+) the increase in tone, stiffness, and soreness was significantly lower than
      in the group not receiving TCC (n = 12; No-TCC). Elasticity varied coherently
      with tone and stiffness.A very intense and protracted sport activity increases
      muscular tone, stiffness, and soreness over time. Topical TCC foam significantly
      attenuates these alterations and might represent an efficient strategy both to
      prevent and manage contractures and their consequences in professional cyclists
      as well in athletes from other disciplines involving similar workloads.

PMID- 28746233
TI  - Preoperative thromboelastometry for the prediction of increased chest tube output
      in cardiac surgery: A retrospective study.
AB  - Bleeding following cardiac surgery is a serious event with potentially life
      threatening consequences. Preoperative recognition of coagulation abnormalities
      and detection of cardiopulmonary bypass (CPB) related coagulopathy could aid in
      the start of preventive treatment strategies that minimize perioperative blood
      loss. Most algorithms that analyze thromboelastometry coagulation tests in
      elective cardiac surgery do not include test results performed before surgery. We
      evaluated preoperative rotational thromboelastometry test results for their
      ability to predict blood loss during and after cardiac surgery.A total of 114
      adult patients undergoing cardiac surgery with CPB were included in this
      retrospective analysis. Each patient had thromboelastometry tests done twice:
      preoperatively, before the induction of anesthesia and postoperatively, 10
      minutes after heparin reversal with protamine after decannulation.Patients were
      placed into 1 of 2 groups depending on whether preoperative thromboelastometry
      parameters deviated from reference ranges: Group 1 [N = 29; extrinsically
      activated test (EXTEM) or INTEM results out of normal range] or Group 2 (N = 85;
      EXTEM and INTEM results within the normal range). We observed that the total
      amount of chest tube output was significantly greater in Group 1 than in Group 2
      (700 mL vs 570 mL, P = .03). At the same time, the preoperative values of
      standard coagulation tests such as platelet count, aPTT, and INR did not indicate
      any abnormalities of coagulation.Preoperative coagulation abnormalities diagnosed
      with thromboelastometry can predict increased chest tube output in the early
      postoperative period in elective adult cardiac surgery. Monitoring of the
      coagulation system with thromboelastometry allows rapid diagnosis of coagulation
      abnormalities even before the start of the surgery. These abnormalities could not
      always be detected with routine coagulation tests.

PMID- 28746235
TI  - The Anterior Intercostal Artery flap: Anatomical and radiological study.

PMID- 28746234
TI  - Outcome of high-intensity focused ultrasound and uterine artery embolization in
      the treatment and management of cesarean scar pregnancy: A retrospective study.
AB  - The aim of the study was to compare the efficacy and safety between high
      intensity focused ultrasound (HIFU) treatment and uterine artery embolization
      (UAE) treatment; we retrospectively analyzed 152 cases with cesarean scar
      pregnancy (CSP). Based on our inclusion and exclusion criteria, 152 patients
      (average age, 31.8 +/- 4.6 years old) with CSP were eligible for the HIFU group
      (85 patients) or the UAE group (77 patients). All patients in 2 groups received
      the treatment with suction curettage under hysteroscopy prior to HIFU or UAE
      treatment and followed up for 12 months. The assessment criteria of treatment
      efficacy included the success rate, intraoperative blood loss, duration of
      vaginal bleeding, normal menstrual function recovery time, time for beta-human
      chorionic gonadotrophin (beta-HCG) back to normal level, duration of hospital
      stays, and other adverse effects. Following up for 12 months, the HIFU group was
      of less intraoperative blood loss (76.38 +/- 22.89 vs 114.42 +/- 30.34 mL, P =
      .02), shorter duration of postoperative vaginal bleeding (11.28 +/- 3.65 vs 15.77
      +/- 7.24 days, P = .01) and lower adverse effects rate comparing to the UAE
      group. However, the HIFU group have longer time for the beta-HCG recovery to the
      normal level (35.28 +/- 9.86 vs 29.91 +/- 7.29, P = .03). Additionally, there
      were no significantly statistic differences between the 2 groups in baseline
      characteristics, success rate, and average time of gestational sac disappeared
      and menstrual recovery and hospital stay. Thus, we concluded that the method of
      both HIFU and UAE combined with suction curettage under hysteroscopy is safe and
      effective in the management of CSP. Meanwhile, HIFU is a better therapy option
      than UAE for those women who are seeking complete relieve of symptom to gain
      fertility.

PMID- 28746237
TI  - Abdominoplasty with Lymphatic Microsurgery for Patients with Secondary Lower
      Extremity Lymphedema.
AB  - BACKGROUND: Patients with secondary lower extremity lymphedema (LEL) often
      develop suprapubic lymphedema. We developed a novel surgical method of shaping
      the lower abdomen and debulking suprapubic lymphedema with simultaneous
      reconstruction of lymphatic flow in case of LEL. METHODS: A skin incision in a
      fleur-de-lis pattern was performed for horizontal and vertical abdominal skin and
      fat resection. A caudal-based isosceles triangular flap was created on the
      central suprapubic region to reduce wound tension at the intersection of the
      horizontal and vertical incisions. After resection and debulking of the
      suprapubic region, a lymphaticovenular anastomosis (LVA) between the efferent
      lymphatic vessel of the groin node and the superficial inferior epigastric vein
      was created or vascularized lymph node transfer (LNT) to the groin region was
      performed to restore lymphatic flow. LVA and LNT were also performed at the lower
      extremities to improve LEL. Perioperative change in limb volume was evaluated
      using the LEL index, and lymphatic function was evaluated by lymphoscintigraphy.
      RESULTS: Simultaneous abdominoplasty and reconstructive lymphatic microsurgery
      were performed in 11 patients. The LEL index improved perioperatively, with a
      significant difference (p < 0.01). In eight patients who underwent
      lymphoscintigraphy before and after surgery, the lymphatic function was found to
      have not deteriorated in any limb. CONCLUSION: When simultaneous lymphatic
      microsurgeries and careful observation for complications were performed,
      abdominoplasty resulted in good outcomes in patients with LEL and suprapubic
      lymphedema without worsening of lymphedema.

PMID- 28746238
TI  - "Sural nerve splitting in reverse sural artery perforator flap: Anatomical study
      in 40 cadaver legs".
AB  - BACKGROUND: The reverse sural artery perforator flap (RSAPF) has been widely used
      in reconstructions of the lower extremity. However, along with the high rate of
      flap necrosis, sural nerve (SN) injury is one of the most frequent complications.
      This cadaveric study investigated a simple SN preservation technique during
      RSAPF. METHODS: Anatomic dissection of the sural nerve was performed on 40 lower
      legs, from 20 cadavers, to investigate the pattern of SN distribution. The points
      where the lateral sural cutaneous (LSCN) and medial sural cutaneous (MSCN) nerves
      penetrate the deep fascia were measured. The converging point of these nerves
      into the SN was also recorded. Further, the SN was split until no tethering was
      observed, during flap transposition, to simulate SN-sparing RSAPF. RESULTS:
      Twenty-nine legs (72.5%) showed the LSCN and MSCN converging to become the SN
      (combined pattern); 7 (17.5%) and 4 legs (10.0%) demonstrated the diminished and
      parallel types, respectively. The distances between the lateral malleolus and the
      fascia-penetrating point of the LSCN and MSCN were 29.9 +/- 3.3 cm and 18.8 +/-
      5.6 cm, respectively. In the combined type, the point of the LSCN and MSCN
      convergence was 13.6 +/- 4.2 cm from the lateral malleolus. Nerve splitting was
      successfully performed in all combined cases, without injuring the nerve
      fascicles. CONCLUSIONS: The MSCN enters the deep fascia significantly more
      distally than does the LSCN. Further, using nerve splitting, the MSCN can be kept
      intact during RSAPF in cases demonstrating the combined type of SN.

PMID- 28746239
TI  - Late Surgical-Site Infection in Immediate Implant-Based Breast Reconstruction.

PMID- 28746240
TI  - "Does the Organization of Plastic Surgery Units into Independent Departments
      Affect Academic Productivity?"
AB  - BACKGROUND: There is an increased push for plastic surgery units in the United
      States to become independent departments administered autonomously rather than as
      divisions of a multispecialty surgery department. The purpose of this research
      was to determine if there are any quantifiable differences in the academic
      performance of departments versus divisions. METHODS: Using a list of the plastic
      surgery units affiliated with The American Council of Academic Plastic Surgeons
      (ACAPS), unit websites were queried for departmental status and to obtain a list
      of affiliated faculty. Academic productivity was then quantified using the SCOPUS
      database. National Institute of Health (NIH) funding was determined through the
      Research Portfolio Online Reporting Tools database. RESULTS: Plastic surgery
      departments were comparable to divisions in academic productivity, evidenced by a
      similar number of publications per faculty (38.9 versus 38.7; p=0.94), number of
      citations per faculty (692 versus 761; p=0.64), H-indices (9.9 versus 9.9;
      p=0.99), and NIH grants (3.25 versus 2.84; p=0.80), including RO1 grants (1.33
      versus 0.84; p=0.53). There was a trend for departments to have a more equitable
      male to female ratio (2.8 versus 4.1; p=0.06), and departments trained a greater
      number of integrated plastic surgery residents (9.0 versus 5.28; p=0.03).
      CONCLUSIONS: This study demonstrates that the academic performance of independent
      plastic surgery departments is generally similar to divisions, but with nuanced
      distinctions.

PMID- 28746241
TI  - Upper lip reconstruction.
AB  - Reconstruction of an aesthetically acceptable and functional upper lip requires a
      careful consideration of the transverse and vertical soft tissue, muscle and
      skin, deficiency. This review focuses on the reconstructive aspects of the upper
      lip.The functional anatomy of the upper lip is considerably complex and includes
      paired muscles in addition to the orbicularis, elevators of both the upper lip
      and commissure. The muscular action of facial expression recruits different sets
      of these paired muscles. Unlike the aesthetic uniform appearance of the lower lip
      commissure to commissure, the upper lip aesthetics can be divided into a central,
      the philtrum unit, and a lateral upper lip unit. The lateral unit can be further
      subdivided into medial and lateral elements, the medial more fixed and less
      mobile due to attachments superiorly at the alar sill and base. Reconstruction of
      the philtrum is best accomplished with an Abbe flap. Methods to reconstruct the
      lateral unit hinge on location, medial vs. lateral, and defect size.A conceptual
      approach to successful reconstruction of upper lip defects entails the use of a
      classification based on the aesthetic unit, appropriate selection of the
      reconstructive option for a particular defect driven by location and size, and
      careful consideration given to a final result in harmony both transversely and
      vertically with the lower lip and the remainder of the midface.

PMID- 28746242
TI  - Impact of Mindfulness-Based Parenting on Women in Treatment for Opioid Use
      Disorder.
AB  - OBJECTIVES: Mothers with opioid use disorder are at high risk for maladaptive
      parenting. The present observational study aimed to measure the impact of a
      trauma-informed mindfulness-based parenting (MBP) intervention on quality of
      parenting behaviors of mothers primarily with opioid use disorders as well as
      examine associations between exposure to adverse childhood experiences and self
      reported mindful parenting. METHODS: A pretest posttest design was used with
      repeated measures. A total of 160 women were recruited from a substance use
      treatment program into the 12-week-long group-based intervention comprised
      didactic and experiential mindfulness activities. The Keys to Interactive
      Parenting Scale (KIPS) measured quality of parenting behavior, the Adverse
      Childhood Experiences Tool captured history of exposure to childhood trauma, and
      the Interpersonal Mindfulness in Parenting (IM-P) scale measured the degree of
      mindful parenting. Analyses were conducted using multilevel modeling. RESULTS:
      The MBP intervention resulted in clinically significant improvements in KIPS
      total and all subscale scores and an IM-P total score. Data showed higher
      baseline Adverse Childhood Experiences and higher program attendance
      significantly predicted improved overall quality of parenting behaviors at a
      greater rate over time. Higher IM-P scores were associated with greater rate of
      improvement in KIPS total and all subscale scores. CONCLUSIONS: Study findings
      suggest a trauma-informed MBP intervention for parenting women with opioid use
      disorders is associated with significant clinical improvements in quality of
      parenting behavior. Results of this model show promise in supporting parenting of
      mothers receiving treatment for opioid use disorders to enhance bonding and
      parenting.

PMID- 28746243
TI  - Heavy Barbell Hip Thrusts Do Not Effect Sprint Performance: An 8-Week Randomized
      Controlled Study.
AB  - The purpose of this study was to examine the effects of an 8-week barbell hip
      thrust strength training program on sprint performance. Twenty-one collegiate
      athletes (15 males and 6 females) were randomly assigned to either an
      intervention (n = 11, age 27.36 +/- 3.17 years, height 169.55 +/- 10.38 cm,
      weight 72.7+/- 18 kg) or control group (n = 10, age 27.2 +/- 3.36 years, height
      176.2 +/- 7.94 cm, weight 76.39 +/- 11.47 kg). 1RM hip thrust, 40m sprint time,
      and individual 10m split timings: 0-10, 10-20, 20-30, 30-40m, were the measured
      variables; these recorded at both the baseline and post testing time points.
      Following the 8-week hip thrust strength training intervention significantly
      greater 1RM hip thrust scores for the training group were observed (p < 0.001, d
      = 0.77 [mean difference 44.09 kg]), however this failed to translate into changes
      in sprint time for any of the measured distances (all sprint performance
      measures: p > 0.05, r = 0.05 - 0.37). No significant differences were seen for
      the control group for 1RM hip thrust (p = 0.106, d = 0.24 [mean difference 9.4
      kg]) or sprint time (all sprint performance measures: p > 0.05, r = 0.13 - 0.47).
      These findings suggest that increasing maximum hip thrust strength through use of
      the barbell hip thrust does not appear to transfer into improvements in sprint
      performance in collegiate level athletes.

PMID- 28746244
TI  - The effect of unicycle riding course on trunk strength and trunk stability
      functions in children.
AB  - PURPOSE: The aim of the study was to assess the effect of unicycling on trunk
      strength and timing of automatic stability actions of the selected trunk muscles
      (multifidus, obliquus externus, erector spine). METHODS: Twenty healthy 12-year
      old children (12 boys, 8 girls; age 12.1 +/- 0.2 yrs; body height 1.57 +/- 0.05
      m; body mass 52.8 +/- 10.6 kg) were assigned to experimental and control group.
      Experimental group performed a supervised 12-session course of unicycling. Trunk
      strength was measured with a multi-purpose diagnostic machine in frontal and
      sagittal planes in standing position. Trunk reflex responses and anticipatory
      actions were assessed through unexpected loading over the hands and rapid
      shoulder flexion, respectively. RESULTS: After the intervention, strength
      increased significantly (p < 0.01) in the experimental group in all analysed
      positions. A significant interaction effect was observed during trunk extension
      (p < 0.01) and lateral flexion exertions (p < 0.03). Postural reflex latency
      improved significantly (p < 0.001) in the experimental group with a significant
      interaction effect in all analysed muscles (p < 0.001). Anticipatory postural
      adaptations improved significantly (p < 0.05) in multifidus and obliquus externus
      of the experimental group only. CONCLUSION: Unicycling proved to be an effective
      and funny tool to develop proximal stability and strength, which prevents low
      back pain and improves the efficiency of energy transfer between body segments.
      PRACTICAL APPLICATIONS: To improve the efficiency of physical education classes,
      unicycling should be considered a useful tool to increase trunk strength and
      stability among prepubertal children.

PMID- 28746245
TI  - The Physical and Physiological Demands of Elite International Female Field Hockey
      Players During Competitive Match-Play.
AB  - The aim of the current investigation was to quantify the physical and
      physiological demands of elite international female field hockey match-play
      across halves of play. Thirty-eight participants (24 +/- 5 years; 173 +/- 5 cm;
      72 +/- 5 kg) took part in nineteen competitive matches during the 2014 - 2015
      season. Participants were monitored with GPS technology and heart rate monitors.
      Players were categorized based on three different playing positions. Activity was
      categorized into total (m), high-speed running distance (m; >16 km.h) and
      relative distance (m.min) due to the use of rolling substitutions. Heart rate was
      classified based on the percentage of players individual HRpeak determined via a
      Yo-Yo intermittent recovery level 1 test. Players spent on average 44 +/- 7 min
      in match-play. The total distance covered was 5558 +/- 527 m (125 +/- 23 m.min)
      with 589 +/- 160 m (13 +/- 4 m.min) completed at high-speed. Defenders covered a
      greater total distance compared to other positions of play (p <= 0.001). Midfield
      players covered a greater distance at high-speed (p <= 0.001) with the forwards
      having a higher relative distance (p <= 0.001). The HRpeak of the players was 199
      +/- 1 bmin with a mean exercise intensity of 86 +/- 7.8 % of HRpeak. The time
      spent >85% HRpeak decreased significantly across the halves (p = 0.04, eta =
      0.09, Small). Defenders were found to spend more time >85 % HRpeak when compared
      to forwards (p <= 0.001). The current investigation provides normative data that
      coaches should consider when constructing training regimen.

PMID- 28746246
TI  - Acute Effects of Constant-Angle and Constant-Torque Static Stretching on Passive
      Stiffness of the Posterior Hip and Thigh Muscles in Healthy, Young and Old Men.
AB  - The purpose of this study was to examine the acute effects of constant-angle (CA)
      and constant-torque (CT) static stretching on passive stiffness of the posterior
      hip and thigh muscles in healthy, young and old men. Fifteen young (25+/-3 years)
      and 15 old (71+/-4 years) men underwent 2 passive straight-leg raise (SLR)
      assessments before and after 8 min of CA and CT stretching using an isokinetic
      dynamometer. Passive stiffness was calculated during each SLR as the slope of the
      final 10% of the angle-torque curve. The results indicated that passive stiffness
      decreased from pre- to post-stretching for both treatments (P<=0.001-0.002) and
      age groups (P<=0.001-0.046); however, greater decreases were observed for the CT
      than the CA stretching (P=0.045) and for the old than the young men (P<0.001). In
      addition, baseline stiffness was greater for the old compared to the younger men
      (P=0.010) and was also negatively related (r=-0.721;P<0.001) to the changes in
      stiffness from pre- to post-stretching. These findings suggest that holding
      stretches at a constant tension may be a more effective strategy for altering
      passive stiffness of the posterior hip and thigh muscles. The greater stretch
      induced stiffness decreases observed for the older men provide support that acute
      static stretching may be particularly effective for reducing stiffness in the
      elderly. As a result, it may be advantageous to prescribe static stretching prior
      to exercise for older adults, as this may be used to elicit substantial declines
      in passive stiffness, which could help reduce the risk of subsequent injury
      events in this population.

PMID- 28746247
TI  - Do fast older runners pace differently from fast younger runners in the 'new york
      city marathon'?
AB  - Although pacing strategies in the marathon and generally in endurance running
      have been well studied with regards to the effects of age group and performance
      level, little is known for their interaction. Thus, the aim of the present study
      was to examine whether fast runners of different age differ for pacing. Finishers
      (women, n=117,595; men, n=180,487) in the 'New York City' marathon between 2006
      and 2016 were analyzed in 5-year age groups. To examine the effect of
      performance, we created performance groups according to quartiles of average race
      speed (Q1 - the fastest, Q2, Q3 and Q4 - the slowest). A large main effect of
      split on race speed was observed in women and men with the fastest speed in the 5
      10 km split and the slowest in the 35-40 km. Compared to the other performance
      groups, the slowest group had the largest % decrease in speed at 5 km, 10 km, 15
      km and 20 km but the largest % increase in speed at 35 km and 40 km. The fastest
      group had the least decrease during the race and the least increase at 40 km. A
      trivial split*age group interaction on race speed was observed for all
      performance groups in both sexes. This interaction was more pronounced in Q4.
      Based on these findings, coaches should advise their slow master runners to adopt
      age-tailored pacing strategy, whereas their fast master runners should adopt
      similar pacing as the younger fast runners.

PMID- 28746248
TI  - Relationships Between Countermovement Jump Ground Reaction Forces and Jump
      Height, Reactive Strength Index, and Jump Time.
AB  - Barker, LA, Harry, JR, and Mercer, JA. Relationships between countermovement jump
      ground reaction forces and jump height, reactive strength index, and jump time. J
      Strength Cond Res 32(1): 248-254, 2018-The purpose of this study was to determine
      the relationship between ground reaction force (GRF) variables to jump height,
      jump time, and the reactive strength index (RSI). Twenty-six, Division-I, male,
      soccer players performed 3 maximum effort countermovement jumps (CMJs) on a dual
      force platform system that measured 3-dimensional kinetic data. The trial
      producing peak jump height was used for analysis. Vertical GRF (Fz) variables
      were divided into unloading, eccentric, amortization, and concentric phases and
      correlated with jump height, RSI (RSI = jump height/jump time), and jump time
      (from start to takeoff). Significant correlations were observed between jump
      height and RSI, concentric kinetic energy, peak power, concentric work, and
      concentric displacement. Significant correlations were observed between RSI and
      jump time, peak power, unload Fz, eccentric work, eccentric rate of force
      development (RFD), amortization Fz, amortization time, second Fz peak, average
      concentric Fz, and concentric displacement. Significant correlations were
      observed between jump time and unload Fz, eccentric work, eccentric RFD,
      amortization Fz, amortization time, average concentric Fz, and concentric work.
      In conclusion, jump height correlated with variables derived from the concentric
      phase only (work, power, and displacement), whereas Fz variables from the
      unloading, eccentric, amortization, and concentric phases correlated highly with
      RSI and jump time. These observations demonstrate the importance of
      countermovement Fz characteristics for time-sensitive CMJ performance measures.
      Researchers and practitioners should include RSI and jump time with jump height
      to improve their assessment of jump performance.

PMID- 28746249
TI  - Optic Nerve Sheath Meningocele Simulating an Optic Nerve Pit.

PMID- 28746250
TI  - Keratin Horn of the Palpebral Conjunctiva.

PMID- 28746251
TI  - A Case of Lacrimal Sac Septum Presenting With Dacryocystocele.
AB  - Lacrimal sac septum is a rare structural abnormality of the lacrimal system. A 15
      year-old patient presented with epiphora and a mass inferior to the left medial
      canthal tendon. Dacryocystography and CT-dacryocystography revealed a dilated
      lacrimal sac with complete obstruction. A horizontal lacrimal sac septum was
      found in the mid-sac region during endoscopic dacryocystorhinostomy.
      Histopathologic examination of the septum revealed chronic inflammation with
      stratified columnar epithelial cell lining consistent with the lacrimal sac.

PMID- 28746252
TI  - Primary Neuroendocrine Tumor of the Orbit Presenting With Acute Proptosis.
AB  - Primary neuroendocrine tumors of the orbit are exceedingly rare and typically
      present with gradual, progressive exophthalmos. In this report, an otherwise
      healthy 64-year-old woman undergoes resection of a well-differentiated
      neuroendocrine tumor after presenting with acute proptosis. An extensive clinical
      and radiographic evaluation reveals no other evidence of disease, establishing
      the diagnosis of a primary neuroendocrine tumor. The case presentation is
      followed by a brief review of the classification, presentation, and evaluation of
      orbital neuroendocrine tumors.

PMID- 28746253
TI  - A Case of Everolimus-Induced Eyelid Edema.
AB  - Everolimus is a newer generation mammalian target of rapamycin inhibitor approved
      for immunosuppressive use in a number of advanced medical conditions. The authors
      report a unique case of persistent eyelid edema believed to be related to the
      immunosuppressive therapy. The therapy was being well tolerated despite the
      persistent eyelid edema, so the patient underwent a bilateral upper eyelid
      blepharoplasty. The patient responded well with resolution of her eyelid
      dermatochalasis and markedly decreased edema. Everolimus-induced eyelid edema
      should be recognized by clinicians as a potential side effect of the medication.
      Surgical excision of excess eyelid tissue by blepharoplasty can be a successful
      way to manage this side effect.Everolimus (zortress) was initially approved as an
      immunosuppressive agent for renal transplantation patients. Approval for the
      treatment of subependymal giant cell astrocytomas associated with tuberous
      sclerosis, progressive metastatic pancreatic neuroendocrine tumors, human
      epidermal growth factor receptor 2 negative breast cancer in postmenopausal
      woman, liver transplantation patients, and well-differentiated neuroendocrine
      tumors of gastrointestinal or pulmonary origin has followed., Everolimus is a
      derivative of sirolimus (rapamune), and similar to sirolimus acts as an inhibitor
      of mammalian target of rapamycin. Few prior studies have reported eyelid edema
      from sirolomus. Many prior medications have been implicated in eyelid edema
      formation. To date, periocular edema has not been reported as a side effect of
      everolimus. We report a patient with bilateral upper eyelid edema associated with
      everolimus therapy requiring surgical intervention to ameliorate the significant
      skin redundancy and the visual field defect. This report complies with the
      Declaration of Helsinki and Health Insurance Portability and Accountability Act
      regulations.

PMID- 28746254
TI  - Cicatricial Ectropion Secondary to Graft-Versus-Host Disease.
AB  - Ocular complications of graft-versus-host disease are well documented. While skin
      changes due to graft-versus-host disease have been mentioned in the literature,
      cicatricial ectropion has not been previous reported. The authors present a case
      of a 31-year-old male with cicatricial ectropion secondary to graft-versus-host
      disease requiring treatment with a full thickness skin graft.

PMID- 28746255
TI  - Normalization of Congenital Venous Stasis Retinopathy Following Sclerotherapy of
      a Macrocystic Lymphatic Malformation.
AB  - The authors describe, for the first time to their knowledge, a case of a
      congenital macrocystic lymphatic malformation of the orbit with associated venous
      stasis retinopathy that acutely normalized after drainage and sclerotherapy of
      the lesion. Prenatal ultrasound revealed prominence of the left orbital soft
      tissue, and at birth, the patient was noted to have unilateral proptosis,
      tortuous retinal vessels, and intraretinal hemorrhages in all 4 quadrants in the
      left eye. MRI demonstrated a primarily intraconal, multiloculated, T2
      hyperintense mass consistent with a lymphatic malformation. Ultrasound-guided
      cyst aspiration and sclerotherapy was performed, with subsequent improvement of
      the proptosis and resolution of the vessel tortuosity and intraretinal
      hemorrhages. Although venous stasis retinopathy is usually related to central
      retinal vein occlusion or carotid artery occlusive disease, any entity that
      increases orbital venous resistance can generate retinal venous dilation and
      intraretinal hemorrhages, including an orbital lymphatic malformation.

PMID- 28746256
TI  - Successful Treatment of Actinic Granuloma With Pulsed-Dye Laser and Fractionated
      Carbon Dioxide Laser.

PMID- 28746257
TI  - Commentary on Chlorhexidine Keratitis.

PMID- 28746258
TI  - Treatment of Facial Acne Scarring With Fractional Carbon Dioxide Laser in Asians,
      a Retrospective Analysis of Efficacy and Complications.
AB  - BACKGROUND: Fractional carbon dioxide (CO2) laser resurfacing unites the idea of
      fractional photothermolysis with an ablative 10,600-nm wavelength. This
      technology permits effective treatment of acne scarring, with shorter recovery
      and a decreased side effect profile as compared to traditional CO2 laser
      resurfacing. OBJECTIVE: The aims of this study were to study the efficacy and
      safety of fractional CO2 laser for acne scars in Asian patients. METHODS: This
      was a retrospective study of all patients treated with the fractional CO2 laser
      for facial acne scarring between January 2, 2008, and December 31, 2010, at the
      National Skin Centre, Singapore. Data reviewed included sex, age, and severity of
      acne, type of scarring, previous treatment history, frequency of treatments,
      adverse events, and efficacy. RESULTS: Two hundred and ten fractional CO2 laser
      treatments for facial acne scars were performed on 107 patients (65 men and 42
      women, Fitzpatrick skin Types II to V) during the study period. Sixteen of 107
      patients experienced (15.0%) adverse events. The adverse events include
      hyperpigmentation (6.4%), blistering (4.0%), crusting (2.9%), aggravation of
      inflammatory acne lesions (1.7%), and scarring (0.6%). There were no reported
      side effects of hypopigmentation, bacterial or viral infection. Follow-up results
      after final laser treatment showed that 66.4% of patients reported Grade 1 skin
      texture improvement, that is, <25% (n = 71); 30.0% had Grade 2 improvement, that
      is, 25% to 50% improvement (n = 31); 3.7% had Grade 3 improvement, that is, 51%
      to 75% improvement (n = 4); and 0.9% had Grade 4 improvement, that is, >75%
      improvement (n = 1). CONCLUSION: The study demonstrated the efficacy and safety
      of a fractional CO2 laser in the treatment of acne scars in Asian. Future studies
      are required to establish optimum treatment parameters and achieve better
      clinical results.

PMID- 28746259
TI  - Variations in Antibiotic and Azithromycin Prescribing for Children by Geography
      and Specialty-United States, 2013.
AB  - BACKGROUND: Using antibiotics appropriately is critical to slow spread of
      antibiotic resistance, a major public health problem. Children, especially young
      children, receive more antibiotics than other age groups. Our objective was to
      describe antibiotic use in children in the United States and use of azithromycin,
      which is recommended infrequently for pediatric conditions. METHODS: We used
      QuintilesIMS Xponent 2013 data to calculate the number and rate of oral
      antibiotic prescriptions for children by age (0-2, 3-9 and 10-19 years) and
      agent. We used log-binomial regression to calculate adjusted prevalence ratios
      and 95% confidence intervals to determine if specialty and patient age were
      associated with azithromycin selection when an antibiotic was prescribed.
      RESULTS: In 2013, 66.8 million antibiotics were prescribed to US children <=19
      years of age (813 antibiotic prescriptions per 1000 children). Amoxicillin and
      azithromycin were the 2 most commonly prescribed agents (23.1 million courses,
      35% of all antibiotics; 12.2 million, 18%, respectively). Most antibiotics for
      children were prescribed by pediatricians (39%) and family practitioners (15%).
      Family practitioners were more likely to select azithromycin when an antibiotic
      was prescribed in all age groups than pediatricians (for children 0-2 years of
      age: prevalence ratio: 1.79, 95% confidence interval: 1.78-1.80; 3-9 years: 1.40,
      1.40-1.40 and 10-19 years: 1.18, 1.18-1.18). CONCLUSION: Despite infrequent
      pediatric recommendations, variations in pediatric azithromycin use may suggest
      inappropriate antibiotic selection. Public health interventions focused on
      improving antibiotic selection in children as well as reducing antibiotic overuse
      are needed.

PMID- 28746260
TI  - Perinatal HIV Infection and Exposure and Their Association With Dental Caries in
      Nigerian Children.
AB  - BACKGROUND: Although HIV infection is associated with well-known oral
      pathologies, there remains a dearth of comparative studies aimed at determining
      the association between HIV infection/exposure and early childhood caries.
      METHODS: This is a cross-sectional study using a convenience sample of 3 groups
      of children receiving care at a tertiary care hospital in Nigeria. The groups
      include HIV infected (HI), HIV exposed but uninfected and HIV-unexposed and 
      uninfected children 6 through 72 months of age. Medical records were reviewed,
      and caregivers were interviewed for sociodemographic, maternal and birth factors
      as well as early feeding and dietary information. Oral examinations were
      performed by trained dentist examiners. RESULTS: Of 335 children enrolled, 33
      (9.9%) presented with caries. In an adjusted analysis, compared with HIV
      unexposed and -uninfected children, HI children had significantly greater odds of
      having caries (odds ratio = 2.58; 95% confidence interval: 1.04-6.40; P = 0.04),
      but there was no statistically significant difference in HIV exposed but
      uninfected children (odds ratio = 2.01; 95% confidence interval: 0.56-7.23; P =
      0.28). Factors significantly associated with higher caries prevalence include low
      CD4 counts and percentage, older age, longer duration of breastfeeding and
      spontaneous membrane rupture during delivery. CONCLUSIONS: Caries was more
      prevalent in HI children. These findings support the need to target HI children
      for oral health prevention and treatment services particularly in Nigeria and
      other developing countries.

PMID- 28746261
TI  - Rotavirus Infection in the Auckland Region After the Implementation of Universal
      Infant Rotavirus Vaccination: Impact on Hospitalizations and Laboratory
      Implications.
AB  - BACKGROUND: In July 2014, New Zealand introduced universal infant vaccination
      with RotaTeq (Merk & Co.) administered as 3 doses at 6 weeks, 3 and 5 months of
      age. We sought to assess the impact of rotavirus vaccination on gastroenteritis
      (GE) hospitalizations in the greater Auckland region and analyze changes in
      rotavirus testing in the period around vaccine introduction. METHODS:
      Hospitalizations, laboratory testing rates and methods were compared between the
      pre-vaccine period (2009-2013), post-vaccine period (January 2015 to December
      2015) and year of vaccine introduction (2014). RESULTS: There was a 68% decline
      in rotavirus hospitalizations of children <5 years of age after vaccine
      introduction (from 258/100,000 to 83/100,000) and a 17% decline in all-cause
      gastroenteritis admissions (from 1815/100,000 to 1293/100,000). Reductions were
      also seen in pediatric groups too old to have received vaccine. Despite these
      changes, rotavirus testing rates in our region remained static in the year after
      vaccine introduction compared with the 2 prior years, and after vaccine
      introduction, we observed a high rate of false positives 19/58 (33%) in patients
      with reactive rotavirus tests. CONCLUSIONS: Rotavirus vaccine has had a
      significant early impact on gastroenteritis hospitalizations for children in the
      Auckland region. However, continued rotavirus testing at pre-vaccine rates risks
      generating false positive results. Laboratories and clinicians should consider
      reviewing their testing algorithms before vaccine introduction.

PMID- 28746262
TI  - Effect Evaluation of a Randomized Trial to Reduce Infectious Illness and Illness
      related Absenteeism Among Schoolchildren: The Hi Five Study.
AB  - BACKGROUND: Previous school-based hand hygiene interventions have reported to
      successfully reduce infectious illness among schoolchildren. But few studies have
      tested the effect in large populations with adequate statistical power and
      analyses. The aim of this study was to evaluate whether a school-based
      multicomponent intervention to improve handwashing among schoolchildren, the Hi
      Five study, succeeded in reducing infectious illness and illness-related
      absenteeism in schools. METHODS: The Hi Five study was a three-armed cluster
      randomized controlled trial involving 43 randomly selected Danish schools; two
      intervention arms involving 14 schools each, and 15 control schools. Infectious
      illness days, infectious illness episodes and illness-related absenteeism were
      estimated in multilevel regressions, based on available cases of text messages
      answered by parents and based on questionnaire data reported by schoolchildren,
      respectively. RESULTS: At follow-up, children in the intervention schools did not
      differ from the control schools in number of illness days [odds ratio (OR)I-arm
      I: 0.91 (0.77-1.07) and ORI-arm II: 0.94 (0.79-1.12)] and illness episodes [ORI
      arm I: 0.95 (0.81-1.11) and ORI-arm II: 0.98 (0.84-1.16)] or in reporting illness
      related absenteeism [ORI-arm I: 1.09 (0.83-1.43) & ORI-arm II: 1.06 (0.81-1.40)].
      CONCLUSIONS: The multicomponent Hi Five intervention achieved no difference in
      the number of illness days, illness episodes or illness-related absenteeism among
      children in intervention schools compared with control schools. It is noteworthy
      that one of the main components in the intervention, a mandatory daily
      handwashing before lunch, was only implemented by 1 of 3 of teachers in
      intervention schools.

PMID- 28746263
TI  - Treatment Outcomes of Children With HIV Infection and Drug-resistant TB in Three
      Provinces in South Africa, 2005-2008.
AB  - OBJECTIVE: To describe outcomes of HIV-infected pediatric patients with drug
      resistant tuberculosis (DR TB). METHODS: Demographic, clinical and laboratory
      data from charts of pediatric patients treated for DR TB during 2005-2008 were
      collected retrospectively from 5 multi-DR TB hospitals in South Africa. Data were
      summarized, and Pearson chi test or Fisher exact test was used to assess
      differences in variables of interest by HIV status. A time-to-event analysis was
      conducted using days from start of treatment to death. Variables of interest were
      first assessed using the Kaplan-Meier method. Cox proportional hazard models were
      fit to estimate crude and adjusted hazard ratios. RESULTS: Of 423 eligible
      participants, 398 (95%) had culture-confirmed DR TB and 238 (56%) were HIV
      infected. A total of 54% were underweight, 42% were male and median age was 10.7
      years (interquartile range: 5.5-15.3). Of the 423 participants, 245 (58%) were
      successfully treated, 69 (16%) died, treatment failed in 3 (1%), 36 (9%) were
      lost to follow-up and 70 (17%) were still on treatment, transferred or had
      unknown outcomes. Time to death differed by HIV status (P = 0.008), sex (P <
      0.001), year of tuberculosis diagnosis (P = 0.05) and weight status (P = 0.002).
      Over the 2-year risk period, the adjusted rate of death was 2-fold higher among
      participants with HIV compared with HIV-negative participants (adjusted hazard
      ratio = 2.28; 95% confidence interval: 1.11-4.68). CONCLUSIONS: Male, underweight
      and HIV-infected children with DR TB were more likely to experience death when
      compared with other children with DR TB within this study population.

PMID- 28746264
TI  - Trends in Otitis Media and Myringotomy With Tube Placement Among American Indian
      and Alaska Native Children and the US General Population of Children After
      Introduction of the 13-valent Pneumococcal Conjugate Vaccine.
AB  - BACKGROUND: American Indian/Alaska Native (AI/AN) children have experienced
      higher otitis media (OM) outpatient visit rates than other US children. To
      understand recent trends, we evaluated AI/AN OM rates before and after 13-valent
      pneumococcal conjugate vaccine introduction. METHODS: We analyzed outpatient
      visits listing OM as a diagnosis among AI/AN children <5 years of age from the
      Indian Health Service National Patient Information Reporting System for 2010
      2013. OM outpatient visits for the general US child population <5 years of age
      were analyzed using the National Ambulatory Medical Care and National Hospital
      Ambulatory Care Surveys for 2010-2011. RESULTS: The 2010-2011 OM-associated
      outpatient visit rate for AI/AN children (63.5 per 100/year) was similar to 2010
      2011 rate for same-age children in the general US population (62.8) and decreased
      from the 2003 to 2005 AI/AN rate (91.4). Further decline in AI/AN OM visit rates
      was seen for 2010-2011 to 2012-2013 (P < 0.0001). The AI/AN infant OM visit rate
      (130.5) was 1.6-fold higher than the US infant population. For 2010-2011, the
      highest AI/AN OM visit rate for <5 year olds was from Alaska (135.0).
      CONCLUSIONS: AI/AN <5-year-old OM visits declined by one third from 2003-2005 to
      2010-2011 to a rate similar to the US general population <5 years. However, the
      AI/AN infant OM rate remained higher than the US infant population. The highest
      AI/AN <5-year-old OM rate occurred in Alaska.

PMID- 28746265
TI  - Prevalence of Rubella Antibodies Among Children in the Democratic Republic of the
      Congo.
AB  - BACKGROUND: While generally mild in children, rubella infection in early
      pregnancy can lead to miscarriage, fetal death or congenital rubella syndrome.
      Rubella vaccination is not yet available as a part of routine immunization in the
      Democratic Republic of the Congo (DRC), and the burden of infection is unknown.
      METHODS: In collaboration with the 2013-2014 DRC Demographic and Health Survey, a
      serosurvey was carried out to assess population immunity to vaccine-preventable
      diseases. Dry blood spot samples collected from children 6-59 months of age were
      processed using the Dynex Technologies Multiplier FLEX chemiluminescent
      immunoassay platform (Dynex Technologies, Chantilly, VA). RESULTS: Among the 7195
      6- to 59-month-old children, 33% were positive and <1% indeterminate for rubella
      antibodies in weighted analyses. Seroprevalence was positively associated with
      age of the child and province, with seropositivity highest in Bandundu (53%) and
      lowest in Kasai-Oriental (20%). In multivariate analyses, serologic evidence of
      infection was associated with age of the mother and child, socioeconomic status
      and geographic location. CONCLUSIONS: Rubella infection is prevalent among
      children in the DRC, and while most seroconversion occurs in young children, a
      significant proportion of children remain at risk and may enter reproductive age
      susceptible to rubella infection. While not currently in place, implementation of
      a surveillance program will provide improved estimates of both rubella virus
      circulation and the burden of congenital rubella syndrome. Such information will
      play an important role in future policy decisions, vaccine delivery strategies
      and may provide a basis upon which the effectiveness of rubella antigen
      introduction may be assessed.

PMID- 28746266
TI  - Quality-of-Life Outcomes Improve with Nipple-Sparing Mastectomy and Breast
      Reconstruction.
AB  - BACKGROUND: Loss of the nipple-areola complex can be psychologically and sexually
      devastating. Nipple-sparing mastectomy provides robust cosmetic results, but few
      studies have investigated the quality-of-life outcomes associated with it.
      METHODS: The authors performed an institutional review board-approved
      retrospective study of 32 patients who underwent nipple-sparing mastectomy with
      implant-based or autologous reconstruction and 32 control patients who underwent
      non-nipple-sparing mastectomy with reconstruction matched by reconstruction type
      and operative period. They then compared premastectomy and postreconstruction
      responses to the BREAST-Q, a validated and breast reconstruction-specific quality
      of-life questionnaire, within and between their study and control populations.
      RESULTS: The nipple-sparing and non-nipple-sparing mastectomy groups were
      statistically similar in terms of mean age [49.9 +/- 8.5 years (range, 36 to 69
      years) and 47.7 +/- 10.3 years (range, 26 to 68 years) (p = 0.29), respectively]
      and mean body mass index [24.3 +/- 3.5 kg/m (range, 17.9 to 33.7 kg/m) and 25.5
      +/- 5.4 kg/m (range, 19.2 to 39.2 kg/m) (p = 0.29), respectively]. There were no
      significant between-group differences in occurrence of postreconstruction
      complications. The authors found significantly higher mean postreconstruction
      scores in the nipple-sparing mastectomy group within the Satisfaction with
      Breasts (p = 0.039) and the Satisfaction with Outcome (p = 0.017) domains.
      Finally, they noted higher median postreconstruction scores in the nipple-sparing
      mastectomy group within the Psychosocial Well-being (p = 0.043) and Satisfaction
      with Breasts (p = 0.004) domains. CONCLUSIONS: Psychological concerns regarding
      malignancy may negatively impact premastectomy patient quality of life.
      Reconstructive surgery improves patients' postmastectomy quality of life. Nipple
      sparing mastectomy appears to provide significantly better improvement in
      postreconstruction quality of life, specifically in the Satisfaction with Breasts
      and Satisfaction with Outcome domains of the BREAST-Q, compared with non-nipple
      sparing mastectomies. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 28746267
TI  - The Baltodano Breast Reduction Score: A Nationwide, Multi-Institutional,
      Validated Approach to Reducing Surgical-Site Morbidity.
AB  - BACKGROUND: Breast reduction remains associated with significantly higher rates
      of overall morbidity, superficial surgical-site infections, and wound
      disruptions. The authors developed a validated risk model to identify patients at
      higher risk for postoperative surgical-site morbidity after breast reduction.
      METHODS: A retrospective review was performed of all women undergoing breast
      reduction from the American College of Surgeons National Surgical Quality
      Improvement Program 2005 to 2012 data. Surgical-site morbidity included surgical
      site infection and wound disruption events. Stepwise multivariable logistic
      regression identified risk factors associated with surgical-site morbidity. The
      model was validated using bootstrap replications (n = 100) and the Hosmer
      Lemeshow test, and converted into the Baltodano breast reduction score, a
      clinical risk tool predictive of surgical-site morbidity. RESULTS: The authors
      identified 7068 breast reductions. Rate of 30-day surgical-site morbidity was
      3.98 percent. Independent risk factors included resident participation (OR, 1.5;
      95 percent CI, 1.1 to 2.0; p = 0.004), body mass index (for every 5-unit
      increase: OR, 1.3; 95 percent CI, 1.1 to 1.4; p < 0.001), smoking (OR, 1.6; 95
      percent CI, 1.1 to 2.4; p = 0.014), steroid use (OR, 3.5; 95 percent CI, 1.4 to
      8.4; p = 0.006), and operation in the third quarter of the year (OR, 1.5; 95
      percent CI, 1.1 to 1.9; p = 0.014). The factors were integrated into the
      Baltodano score, ranging from 0 to 16. The predicted probability of surgical-site
      morbidity associated with each risk score was estimated. Predicted and observed
      risks of surgical-site morbidity were highly comparable. CONCLUSIONS: The authors
      present the Baltodano breast reduction score, a validated risk-stratification
      tool for predicting 30-day surgical-site morbidity following breast reduction
      using data that are readily available to the clinician. This may allow targeted
      screening and intervention in high-risk patients, better counseling, selective
      resident participation, and ultimately a decrease in overall health care costs.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 28746268
TI  - 101 Consecutive Profunda Artery Perforator Flaps in Breast Reconstruction:
      Lessons Learned with Our Early Experience.
AB  - BACKGROUND: Free and local flaps based on the profunda artery perforators were
      first used for reconstruction of pressure sores, burn contractures, and extremity
      wounds. Recently, a revised profunda artery perforator flap was introduced for
      breast reconstruction. However, despite increasing reports of the use of the
      flap, it remains a rarely used option. The authors present their early experience
      with the first 101 profunda artery perforator flaps used for breast
      reconstruction at their institution. METHODS: The authors conducted a
      retrospective review of the first 101 profunda artery perforator flaps at their
      institution. Patient demographics, perioperative data, and postoperative
      complications were recorded and analyzed. RESULTS: One hundred one consecutive
      profunda artery perforator flaps were used to reconstruct 96 breasts in 56
      patients. In 42 breasts, the flap was used in conjunction with another flap-with
      a deep inferior epigastric perforator flap (n = 36), a superior gluteal artery
      perforator flap (n = 1), or as stacked profunda artery perforator flaps (n = 5).
      Mean flap weight was 425 g (range, 170 to 815 g), and mean patient body mass
      index was 26.8 kg/m (range, 18.2 to 42.3 kg/m). Complications included total flap
      loss (2 percent), donor-site cellulitis (5.9 percent), and donor-site wound
      dehiscence (10.9 percent). CONCLUSIONS: The profunda artery perforator flap is a
      safe and reliable option for breast reconstruction. Flap size is adequate for
      breast reconstruction in appropriately selected patients. Furthermore, it can be
      combined with other flaps when additional volume or skin requirements are
      present. Flap and donor-site complications are comparable to those of other free
      tissue breast reconstruction options. It is a clear second option to the deep
      inferior epigastric perforator flap for autologous tissue reconstruction.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 28746269
TI  - Transversus Abdominis Plane Blocks with Single-Dose Liposomal Bupivacaine in
      Conjunction with a Nonnarcotic Pain Regimen Help Reduce Length of Stay following
      Abdominally Based Microsurgical Breast Reconstruction.
AB  - BACKGROUND: Side effects associated with use of postoperative narcotics for pain
      control can delay recovery after abdominally based microsurgical breast
      reconstruction. The authors evaluated a nonnarcotic pain control regimen in
      conjunction with bilateral transversus abdominis plane blocks on facilitating
      early hospital discharge. METHODS: A retrospective analysis was performed of
      consecutive patients who underwent breast reconstruction using abdominally based
      free flaps, with or without being included in a nonnarcotic protocol using
      intraoperative transversus abdominis plane blockade. During this period, the use
      of locoregional analgesia evolved from none (control), to continuous bupivacaine
      infusion transversus abdominis plane and catheters, to single-dose transversus
      abdominis plane blockade with liposomal bupivacaine solution. Demographic
      factors, length of stay, inpatient opioid consumption, and complications were
      reported for all three groups. RESULTS: One hundred twenty-eight consecutive
      patients (182 flaps) were identified. Forty patients (62 flaps) were in the
      infusion-liposomal bupivacaine group, 48 (66 flaps) were in the single-dose
      blockade-catheter group, and 40 (54 flaps) were in the control group. The
      infusion-liposomal bupivacaine patients had a significantly shorter hospital stay
      compared with the single-dose blockade-catheter group (2.65 +/- 0.66 versus 3.52
      +/- 0.92 days; p < 0.0001) and the control group (2.65 +/- 0.66 versus 4.05 +/-
      1.26 days; p < 0.0001). There was no significant difference in flap loss or major
      complications among groups. CONCLUSIONS: When used as part of a nonnarcotic
      postoperative pain regimen, transversus abdominis plane blocks performed with
      single injections of liposomal bupivacaine help facilitate early hospital
      discharge after abdominally based microsurgical breast reconstruction. A trend
      toward consistent discharge by postoperative day 2 was seen. This could result in
      significant cost savings for health care systems. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, III.

PMID- 28746270
TI  - Facial Nerve Supply to the Orbicularis Oculi around the Lower Eyelid: Anatomy and
      Its Clinical Implications.
AB  - BACKGROUND: The motor innervation of the lower orbicularis oculi has not been
      clearly established. There is a discrepancy between anatomical descriptions and
      clinical outcomes of the motor innervation of the pretarsal orbicularis oculi
      muscle. Therefore, the purposes of this study were to identify every motor and
      sensory nerve of the lower eyelid, and to reveal the detailed motor nerve
      pathways toward the medial canthal area. METHODS: Fresh cadaver dissections were
      performed on 50 hemifaces under a surgical microscope. Submuscular and
      intramuscular nerves of the lower eyelid were identified, and the pathways of
      facial nerves that ran toward the medial canthus were traced. RESULTS: Vertical
      submuscular nerves at the lower eyelid originated from the infraorbital foramen,
      indicating that all were sensory nerves. The zygomatic branch of the facial nerve
      traveled obliquely through the anterior cheek and supplied the orbicularis oculi
      of the lower eyelid and the medial portion of the upper eyelid. Its route was
      defined as a clinically useful line, the medial orbicularis motor line. In
      addition, the nerve innervating the pretarsal orbicularis oculi arose at the
      superomedial preseptal area and extended horizontally and laterally.
      Interestingly, the angular nerve appeared not to innervate the palpebral
      orbicularis oculi. CONCLUSIONS: In the lower eyelid, the vertical sensory and the
      oblique motor nerve supplies are independent and clearly distinguished in aspect
      of their own routes. The medial orbicularis motor line represents the motor route
      to the medial portion of the orbicularis oculi. These results might provide
      valuable knowledge about surgical anatomy for safe lower blepharoplasty with or
      without midface lift.

PMID- 28746271
TI  - Facial Assessment and Injection Guide for Botulinum Toxin and Injectable
      Hyaluronic Acid Fillers: Focus on the Upper Face.
AB  - Techniques for the administration of injectable fillers and neuromodulators for
      facial aesthetic rejuvenation and enhancement continue to evolve. As the number
      of physicians with limited experience in providing aesthetic treatments expands,
      the need for guidance and training from more experienced injectors has become
      apparent. The use of a slow, careful, and methodical injection technique is
      imperative in all treatment settings and for all facial areas. Constant attention
      to local anatomy, particularly arteries, veins, and nerve bundles, is critical
      for minimizing complications. This first article of a three-part series addresses
      techniques and recommendations for aesthetic treatment of the upper face.
      Traditionally, the upper face has been considered a basic area for treatment with
      neuromodulators but an advanced area for treatment with fillers. Injectable
      fillers may be used for temple volumization, eyebrow shaping, and forehead
      contouring. Neuromodulators are well suited for diminishing the appearance of
      dynamic facial lines such as forehead, glabellar, and crow's feet lines, and
      eyebrow lifting and eye-aperture widening. These techniques may be used
      independently or together, sequentially or concurrently, to address rejuvenation
      of individual or multiple facial regions. Overall, this series provides a
      practical framework of techniques for physicians who desire to perform safe and
      effective aesthetic treatments using a multimodal approach.

PMID- 28746272
TI  - Extended Transconjunctival Lower Eyelid Blepharoplasty with Release of the Tear
      Trough Ligament and Fat Redistribution.
AB  - BACKGROUND: The transconjunctival lower eyelid blepharoplasty is advantageous for
      its quick recovery and low complication rates. Conventional techniques rely on
      fat removal to contour the lower eyelid. This article describes the authors'
      extended transconjunctival lower eyelid blepharoplasty technique that takes
      dissection beyond the orbital rim to address aging changes on the midcheek.
      METHODS: From December of 2012 to December of 2015, 54 patients underwent this
      procedure. Through a transconjunctival incision, the preseptal space was entered
      and excess orbital fat pads were excised. Medially, the origins of the palpebral
      part of the orbicularis oculi, the tear trough ligament, and orbital part of the
      orbicularis oculi were sequentially released, connecting the dissection with the
      premaxillary space. More laterally, the orbicularis retaining ligament was
      released, connecting the dissection with the prezygomatic space. Excised orbital
      fat was then grafted under the released tear trough ligament to correct the tear
      trough deformity. When the patients had significant maxillary retrusion,
      structural fat grafting was performed at the same time. RESULTS: The mean follow
      up was 10 months. High satisfaction was noted among the patients treated with
      this technique. The revision rate was 2 percent. Complication rates were low. No
      chemosis, prolonged swelling, lower eyelid retraction, or ectropion was seen in
      any patients. CONCLUSION: The extended transconjunctival lower blepharoplasty
      using the midcheek soft-tissue spaces is a safe and effective approach for
      treating patients presenting with eye bags and tear trough deformity. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 28746273
TI  - Discussion: Extended Transconjunctival Lower Eyelid Blepharoplasty with Release
      of the Tear Trough Ligament and Fat Redistribution.

PMID- 28746274
TI  - Male-to-Female Sex Reassignment Surgery Using the Combined Technique Leads to
      Increased Quality of Life in a Prospective Study.
AB  - BACKGROUND: The authors' previous research showed that various plastic surgical
      procedures can increase a patient's quality of life in its different aspects. In
      a prospective setting, they evaluated whether sex reassignment surgery has
      similar effects for male-to-female transgender patients compared to baseline data
      before sex reassignment surgery. METHODS: All 39 patients who underwent their
      first-stage male-to-female sex reassignment surgery between October of 2012 and
      January of 2014 received one set of questionnaires preoperatively (time 0) and
      approximately 6 months after their final operation (time 1). Each set contained
      self-developed, indication-specific questions combined with the standardized
      validated Questions on Life Satisfaction, Modules (German version) questionnaire,
      the Freiburg Personality Inventory, the Rosenberg Self-Esteem Scale, and the
      Patient Health Questionnaire, which were compared to available norm data.
      RESULTS: The mean patient age was 38.6 years. The majority of the patients were
      highly educated, childless, and single. Significant improvements were found in
      the Questions on Life Satisfaction, Modules (German version), especially for the
      items "partnership," "ability to relax," "energy," "freedom from anxiety,"
      "hair," "breast," and "penis/vagina" (p < 0.01). Furthermore, the patients
      appeared more emotionally stable (p = 0.03), showed higher self-esteem (p =
      0.01), and showed much lower depression/anxiety (p < 0.01). CONCLUSIONS: The
      positive study findings were confirmed with the results from prior retrospective
      studies. However, medical literature focuses largely on surgical and functional
      satisfaction and not overall quality of life. In addition, standardized
      questionnaires are used rarely and solely retrospectively, with the risk of
      recall bias. The increased quality of life of transgender women postoperatively
      endorses sex reassignment surgery as a valuable option for these patients.
      CLINICAL QUESTON/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 28746275
TI  - Finesse in Nasal Tip Refinement.
AB  - Nasal tip refinement is one of the most difficult aspects of rhinoplasty surgery.
      In this article, the senior author (R.J.R.) presents his technique for nasal tip
      analysis and identifies the factors that contribute to nasal tip shape. Various
      techniques for nasal tip modification using both sutures and soft cartilage
      grafts are described to help produce optimal results.

PMID- 28746276
TI  - BFACE: A Framework for Evaluating Breast Aesthetics.
AB  - Although much has been written about breast aesthetics, the literature lacks a
      simple yet systematic and comprehensive approach for preoperative breast
      assessment. With use of the mnemonic "BFACE," the breast surgeon will analyze the
      bony skeleton and the breast footprint, areola, conus, and envelope. The authors
      present a thorough review of the important parameters that define the ideal
      breast, and several techniques for perceiving asymmetries more clearly. Strategic
      surgical planning is enabled by accurate perception.

PMID- 28746277
TI  - Auricular Tissue Engineering Using Osteogenic Differentiation of Adipose Stem
      Cells with Small Intestine Submucosa.
AB  - BACKGROUND: Ear reconstruction remains a challenge for plastic surgeons. A tissue
      engineering approach could provide another route for obtaining shape maintenance
      in neoauricular tissue. METHODS: The authors designed a novel tissue-engineering
      auricular construct by culturing human adipose stem cells, which differentiated
      into osteocytes but not chondrocytes, in small intestine submucosa scaffolds. The
      authors evaluated cell growth potential and mechanical properties. An ear-shaped
      construct was created in vitro and then implanted in the backs of nude mice. The
      histology, cellularity, neovascularization, mechanical properties, and ear shape
      maintenance were investigated. RESULTS: In vitro, human adipose stem cells could
      be successfully seeded in the small intestine submucosa and differentiated toward
      osteogenesis. The ear-shaped human adipose stem cell/small intestine submucosa
      construct could maintain its shape in vivo up to 1 year. Alizarin Red S staining
      confirmed osteogenic differentiation. CD31 stain showed prominent angiogenesis in
      the human adipose stem cell/small intestine submucosa construct at 6 months and
      persistence up to 1 year. h-MHC stain revealed the maintenance of cellularity at
      6 months and persistence up to 1 year. The mechanical properties were similar to
      those of native ear cartilage. CONCLUSION: The authors' study found that the
      combination of human adipose stem cells and small intestine submucosa could
      provide a more durable ear-shaped construct in vivo. The mechanical properties,
      shape, and cellularity were maintained in the constructs for up to 12 months.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 28746278
TI  - TLR4 Inactivation in Myeloid Cells Accelerates Bone Healing of a Calvarial Defect
      Model in Mice.
AB  - BACKGROUND: Toll-like receptor 4 (TLR4) has been implicated in inflammation
      induced bone destruction in various chronic bone diseases; however, its direct
      influence on bone healing is not well understood. The authors' previous study
      showed accelerated bone healing with higher osteoclastogenesis gene expression in
      toll-like receptor 4 knockout mice (TLR4). This study aimed to further elucidate
      the underlying cellular mechanisms during fracture healing by generating a
      myeloid cell-specific toll-like receptor 4 knockout model (Lyz-TLR4 mice).
      METHODS: Calvarial defects, 1.8 mm in diameter, were created in wild-type, TLR4,
      and Lyz-TLR4 mice. Bone healing was investigated using micro-computed tomography
      and histologic, histomorphometric, and immunohistochemistry analyses. Primary
      bone marrow-derived cells were also isolated from wild-type, TLR4, and Lyz-TLR4
      mice to measure their osteoclast differentiation and resorption properties.
      RESULTS: A similar faster bone healing response, with active intramembranous bone
      formation, intense osteopontin staining, and more osteoblast infiltration, was
      observed in TLR4 and Lyz-TLR4 mice. Tartrate-resistant acid phosphatase staining
      showed more osteoclast infiltration in Lyz-TLR4 mice than in wild-type mice at
      day 7. Primary bone marrow-derived cells isolated from TLR4 and Lyz-TLR4 mice
      presented enhanced osteoclastogenesis and resorption activity compared with those
      from wild-type mice. Comparable M0, M1, and M2 macrophage infiltration was found
      among all groups at days 1, 4, and 7. CONCLUSIONS: This study revealed that
      inactivation of toll-like receptor 4 in myeloid cells enhanced osteoclastogenesis
      and accelerated healing response during skull repair. Together with the role of
      toll-like receptor 4 in inflammation-mediated bone destruction, it suggests that
      toll-like receptor 4 might regulate inflammation-induced osteoclastogenesis under
      different clinical settings.

PMID- 28746279
TI  - Thy1 (CD90) Expression Is Elevated in Radiation-Induced Periprosthetic Capsular
      Contracture: Implication for Novel Therapeutics.
AB  - BACKGROUND: Capsular contracture is a devastating complication of postmastectomy
      implant-based breast reconstruction. Unfortunately, capsular contracture rates
      are drastically increased by targeted radiotherapy, a standard postmastectomy
      treatment. Thy1 (also called CD90) is important in myofibroblast differentiation
      and scar tissue formation. However, the impact of radiotherapy on Thy1 expression
      and the role of Thy1 in capsular contracture are unknown. METHODS: The authors
      analyzed Thy1 expression in primary human capsular tissue and primary fibroblast
      explants by real-time quantitative polymerase chain reaction, Western blotting,
      and immunohistochemistry. Thy1 was depleted using RNA interference to determine
      whether Thy1 expression was essential for the myofibroblast phenotype in capsular
      fibroblasts. Furthermore, human capsular fibroblasts were treated with a new
      antiscarring compound, salinomycin, to determine whether Thy1 expression and
      myofibroblast formation were blocked by salinomycin. RESULTS: In this article,
      the authors show that radiation therapy significantly increased Thy1 mRNA and
      protein expression in periimplant scar tissue. Capsular fibroblasts explanted
      from scar tissue retained the ability to make the myofibroblast-produced scar
      forming components collagen I and alpha-smooth muscle actin. Depletion of Thy1
      decreased the fibrotic morphology of capsular fibroblasts and significantly
      decreased alpha-smooth muscle actin and collagen levels. Furthermore, the authors
      show for the first time that salinomycin decreased Thy1 expression and prevented
      myofibroblast formation in capsular fibroblasts. CONCLUSIONS: These data reveal
      that ionizing radiation-induced Thy1 overexpression may contribute to increased
      capsular contracture severity, and fibroblast scar production can be ameliorated
      through targeting Thy1 expression. Importantly, the authors' new results show
      promise for the antiscarring ability of salinomycin in radiation-induced capsular
      contracture. CLINCAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 28746280
TI  - Discussion: Autologous Fat Transfer for Thumb Carpometacarpal Joint
      Osteoarthritis: A Prospective Study.

PMID- 28746281
TI  - Corticosteroid Injections for Carpal Tunnel Syndrome: Long-Term Follow-Up in a
      Population-Based Cohort.
AB  - BACKGROUND: Corticosteroid injection is a recommended treatment option for carpal
      tunnel syndrome, before considering surgery. Nevertheless, injections remain
      controversial because there is strong evidence of only short-term benefits. This
      study aimed to determine the reintervention rate and to identify prognostic
      indicators for subsequent treatment after corticosteroid injection for carpal
      tunnel syndrome. METHODS: This study evaluated residents of Olmsted County
      treated with a corticosteroid injection for carpal tunnel syndrome between 2001
      and 2010. Treatment failure was the primary outcome of interest. Two definitions
      for failure were examined: (1) the patient receiving subsequent procedural
      intervention and (2) the patient undergoing carpal tunnel release. Survival was
      estimated using Kaplan-Meier methods, and association of covariates with
      increased failure was modeled using Cox proportional hazards regression. RESULTS:
      The study included 774 affected hands in 595 patients. The median follow-up
      period was 7.4 years. Reintervention was performed in 68 percent of cases, of
      which 63 percent resulted in eventual surgery. Injectate volume was significant
      for the outcome of any retreatment [hazard ratio, 0.879 (95 percent CI, 0.804 to
      0.96)] and surgery [hazard ratio, 0.906 (95 percent CI, 0.827 to 0.99)].
      Rheumatoid arthritis was also significant in both models, with a hazard ratio of
      0.627 (95 percent CI, 0.404 to 0.97) for any retreatment and 0.493 (95 percent
      CI, 0.292 to 0.83) for surgery. CONCLUSIONS: In this cohort, 32 percent of
      patients did not receive subsequent treatment after a single injection, which
      indicates that there is a therapeutic role for corticosteroid injections in
      treating carpal tunnel syndrome. Further research is necessary to identify those
      patients who will benefit from an injection, to provide more individually
      tailored treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 28746282
TI  - Outcomes of Muscle Brachialis Transfer to Restore Finger Flexion in Brachial
      Plexus Palsy.
AB  - BACKGROUND: In adults with lower trunk brachial plexus injury, proximal nerve
      surgery for restoration of prehension demonstrates poor outcomes secondary to
      long distances required for nerve regeneration and time-dependent degradation of
      motor endplates. Options for reconstruction are limited to distal tendon or nerve
      transfers and free-functioning muscle transfers. In this article, the authors
      describe the long-term outcomes of brachialis muscle-to-flexor digitorum
      profundus transfer to restore prehension in patients with traumatic lower trunk
      brachial plexus injuries. METHODS: Eighteen adult patients with lower trunk
      brachial plexus palsy underwent brachialis muscle-to-flexor digitorum profundus
      transfer with the goal of restoring rudimentary prehensile function at a single
      institution. The patients were followed throughout their recovery with functional
      outcomes and patient satisfaction ratings. RESULTS: Brachialis muscle transfer
      resulted in restoring modified British Medical Research Council grade 3 or better
      function in 11 of 18 patients and grade 4 function in eight of 18 patients.
      Eleven of the 18 patients demonstrated a postoperative functional grasp for
      assistance with activities of daily living. Overall patient satisfaction
      following brachialis muscle transfer was 56 percent. Patient preoperative wrist
      extension (p < 0.018) and finger extension (p < 0.029) strength correlated with
      improved outcomes, whereas concomitant upper extremity fracture (p < 0.023) was
      associated with poorer outcomes. CONCLUSIONS: Brachialis muscle transfer is an
      option for reconstruction of prehensile function in patients with lower trunk
      brachial plexus palsy with preserved wrist extension. Brachialis muscle transfer
      is particularly useful in patients who are poor candidates for microsurgical free
      functioning muscle transfer for grasp; however, its functional outcomes are not
      universally successful. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 28746283
TI  - Head Orthosis Therapy in Positional Plagiocephaly: Influence of Age and Severity
      of Asymmetry on Effect and Duration of Therapy.
AB  - BACKGROUND: Only a few studies investigating the optimal time point at which to
      start orthotic treatment for deformational plagiocephaly take into account the
      severity of skull asymmetry. The present study performs a three-dimensional
      analysis of the effects of age and severity of asymmetry on the final outcome.
      METHODS: A total of 144 patients with deformational plagiocephaly treated by
      molding orthosis were examined and divided into three age groups (group I, <24
      weeks; group II, >=24 to <32 weeks; and group III, >=32 weeks) and two severity
      levels (mild to moderate, 30-degree cranial vault asymmetry >=3 mm to <=12 mm;
      and moderate to severe, 30-degree cranial vault asymmetry >12 mm). The extent of
      the reduction of asymmetry was analyzed using three-dimensional
      stereophotogrammetry. RESULTS: Therapy with molding orthosis led to a significant
      reduction in asymmetry in all defined age groups. Efficacy of reduction decreased
      with increasing age. Successful treatment (cranial vault asymmetry index <3.5
      percent) was achieved in 83, 69, and 40 percent of patients with mild to moderate
      asymmetry in groups I, II, and III, respectively; and in 50, 30, and 7 percent of
      patients with moderate to severe asymmetry in groups I, II, and III,
      respectively. The average duration of treatment increased from 18.6 weeks to 25.3
      weeks (age groups I and III). CONCLUSION: Age at the beginning of treatment and
      severity of asymmetry have a definite impact on the duration and effectiveness of
      molding orthosis therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 28746284
TI  - Discussion: Head Orthosis Therapy in Positional Plagiocephaly: Influence of Age
      and Severity of Asymmetry on Effect and Duration of Therapy.

PMID- 28746285
TI  - A Comparative Analysis of Recombinant Human Bone Morphogenetic Protein-2 with a
      Demineralized Bone Matrix versus Iliac Crest Bone Graft for Secondary Alveolar
      Bone Grafts in Patients with Cleft Lip and Palate: Review of 501 Cases.
AB  - BACKGROUND: Alveolar cleft reconstruction using iliac crest bone graft is
      considered standard of care for children with complete cleft lip and palate at
      the time of mixed dentition. Harvesting bone may result in donor-site morbidity
      and additional operating time and length of hospitalization. Recombinant human
      bone morphogenetic protein (rhBMP)-2 with a demineralized bone matrix is an
      alternative bone source for alveolar cleft reconstruction. The authors
      investigated the outcomes of rhBMP-2/demineralized bone matrix versus iliac crest
      bone graft for alveolar cleft reconstruction by reviewing postoperative surgical
      complications and cleft closure. METHODS: A retrospective chart review was
      conducted for 258 rhBMP-2/demineralized bone matrix procedures (mean follow-up,
      2.9 years) and 243 iliac crest bone graft procedures (mean follow-up, 4.1 years)
      on 414 patients over a 12-year period. The authors compared complications, canine
      eruption, and alveolar cleft closure between the two groups. RESULTS: In the
      rhBMP-2/demineralized bone matrix group, one patient required prolonged
      intubation because of intraoperative airway swelling not thought to be caused by
      rhBMP-2, 36 reported facial swelling and one required outpatient steroids as
      treatment, and 12 had dehiscence; however, half of these complications resolved
      without intervention. Twenty-three of the 228 rhBMP-2/demineralized bone matrix
      patients and 28 of the 242 iliac crest bone graft patients required repeated
      surgery for alveolar cleft repair. Findings for canine tooth eruption into the
      cleft site through the graft were similar between the groups. CONCLUSIONS: The
      rhBMP-2/demineralized bone matrix appears to be an acceptable alternative for
      alveolar cleft repair. The authors found no increase in serious adverse events
      with the use of this material. Local complications, such as swelling and minor
      wound dehiscence, predominantly improved without intervention. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 28746286
TI  - Harvesting the Buccal Fat Pad Does Not Result in Aesthetic Deformity in Cleft
      Patients: A Retrospective Analysis.
AB  - BACKGROUND: Buccal fat is often used as a pedicled flap in cleft palate repairs
      to minimize scarring and fortify tenuous closures. Although many surgeons have
      adopted this technique, others have remained circumspect because of the concern
      for subsequent facial asymmetry. METHODS: Patients who underwent cleft palate
      repair using buccal fat pad flaps for closure between 2007 and 2015 were
      reviewed. Only patients with unilateral buccal fat pad flaps and three
      dimensional photography were included. Volumetric analysis was performed on each
      patient to measure cheek volumes of both the flap and nonflap sides. A subgroup
      analysis on cleft palate and bilateral cleft lip and palate patients was
      performed to eliminate the confounding asymmetries of unilateral cleft lip and
      palate patients. Paired t tests were used to determine differences in cheek
      volumes. In addition, three reviewers examined photographs of patients and were
      asked to determine the side of fat pad harvest. RESULTS: Twenty-four patients met
      inclusion criteria. Mean follow-up was 55 months. The volume difference between
      the flap and nonflap sides was not significant (p = 0.81). Subgroup analysis on
      cleft palate and bilateral cleft lip and palate patients did not reveal a volume
      difference between the flap and nonflap sides (p = 0.98). When asked to determine
      which side buccal fat pads were harvested from based on patient photographs, the
      average percentage correct for three independent reviewers was 57 percent and the
      Cohen's kappa was -0.084, indicating poor agreement. CONCLUSION: Although the
      buccal fat pad is thought to play a role in facial aesthetics, the authors found
      no difference in volume between harvest and nonharvest sides, nor was there a
      clinically detectable difference. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 28746287
TI  - Direct Anthropometry of Repaired Bilateral Complete Cleft Lip: A Long-Term
      Assessment.
AB  - BACKGROUND: Repair of bilateral complete cleft lip requires more than following a
      design in a textbook. The operative strategy should incorporate knowledge of
      anticipated nasolabial changes with growth. METHODS: Direct nasolabial
      anthropometry was recorded in 174 children with bilateral complete cleft lip
      before and immediately after primary repair. Serial measurements were taken in 66
      Caucasian patients between the ages of 6 months and 15 years and compared to
      Farkas' normal values. Data for upper philtral width were unavailable; therefore,
      this dimension was measured in 454 nonsyndromic Caucasian male and female
      subjects aged 1 year to adulthood. Rates and types of revision were also
      documented. RESULTS: Inter-medial canthal width stayed above the mean and within
      normal limits throughout puberty. Interalar width was initially narrowed and
      hovered in the high normal range throughout adolescence. Columellar height and
      nasal projection were constructed slightly long and paralleled normal growth.
      Available cutaneous philtral length was used in the primary repair; however, this
      dimension remained short. The philtrum was made narrow and matched normal values
      throughout adolescence. Normal inferior/superior philtral width ratio was 1.60
      for female subjects and 1.59 for male subjects. A full median tubercle was built
      at primary repair but, sometimes in late childhood, necessitated secondary
      augmentation with a dermal graft in 31 of 174 patients (18 percent), usually
      performed in late childhood or adolescence. CONCLUSIONS: Serial anthropometry
      documented postoperative changes in nasolabial dimensions compared to normal
      growth curves. Repair of bilateral complete cleft lip requires primary correction
      of nasal and labial features based on their differential growth, with special
      attention to nasal width, philtral height and proportions, and size of the median
      tubercle. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 28746288
TI  - Using a Second Free Fibula Osteocutaneous Flap after Repeated Mandibulectomy Is
      Associated with a Low Complication Rate and Acceptable Functional Outcomes.
AB  - BACKGROUND: A significant percentage of patients who undergo segmental
      mandibulectomy for head and neck cancer will develop a new or recurrent cancer or
      osteoradionecrosis, necessitating a second mandibulectomy and reconstruction. In
      this scenario, many surgeons are reluctant to perform a reconstruction with an
      osseous flap because of the presumed increased morbidity and complexity. The
      purpose of this study was to evaluate the safety and efficacy of performing a
      second free fibula flap reconstruction after repeated segmental mandibulectomy.
      METHODS: The authors retrospectively reviewed their prospectively maintained
      departmental database for mandible reconstructions performed between 1991 and
      2016, identifying patients who had two sequential free fibula flap
      reconstructions. Patient, disease, and treatment characteristics were recorded
      and analyzed. RESULTS: Twenty patients underwent a second free fibula flap
      reconstruction after a second mandibulectomy. The median follow-up was 72.5
      months (range, 16 to 243 months). Preoperative virtual planning was used more
      often for the second fibula flap compared with the first (50 percent versus 10
      percent; p = 0.004). The mean operative times were statistically similar for the
      first versus second fibula flap (673 minutes versus 586 minutes, respectively; p
      = 0.13). The postoperative complication rates (50 percent versus 30 percent,
      respectively; p = 0.19) and functional outcomes were similar between the first
      and second fibula flap reconstructions. CONCLUSION: Despite the increased
      technical complexity, the use of a second free fibula flap after repeated
      segmental mandibulectomy appears to be safe and to confer no higher risk than
      that for the first fibula flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      IV.

PMID- 28746289
TI  - Management of Scaphoid Fractures.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Understand the epidemiology, classification, and anatomy pertinent to the
      scaphoid. 2. Appropriately evaluate a patient with suspected scaphoid fracture,
      including appropriate imaging. 3. Understand the indications for operative
      treatment of scaphoid fractures, and be familiar with the various surgical
      approaches. 4. Describe the treatment options for scaphoid nonunion and avascular
      necrosis of the proximal pole. SUMMARY: The goal of this continuing medical
      education module is to present the preoperative assessment and the formation and
      execution of a surgical treatment plan for acute fractures of the scaphoid. In
      addition, secondary surgical options for treatment of scaphoid nonunion and
      avascular necrosis are discussed.

PMID- 28746290
TI  - The Associations of Hospital Volume, Surgeon Volume, and Surgeon Experience with
      Complications and 30-Day Rehospitalization after Free Tissue Transfer: A National
      Population Study.
AB  - BACKGROUND: Greater provider volume is associated with better outcomes. There is,
      however, a paucity of evidence on volume-outcome associations for surgical
      complications and 30-day all-cause rehospitalization after free tissue transfer
      or free flap surgery. Surgical complications and frequent rehospitalization are
      important quality indicators that substantially hinder appropriate health care
      spending. The authors hypothesized that increased provider volume and surgeon
      experience are associated with lower complication and hospital readmission rates.
      METHODS: The authors conducted a retrospective cohort study of adults aged 18 to
      64 years who underwent free tissue transfer. They examined 100 percent of all
      free tissue transfers between 2001 and 2012 using Taiwan's national data, and
      used regression modeling to examine associations between volume and outcome. All
      models were adjusted for patient, surgeon, and hospital characteristics. RESULTS:
      Seventeen percent of free tissue transfer operations (4201 of 25,327) had
      complications. Infection was the most prevalent after free tissue transfer (70
      percent), and the 30-day rehospitalization rate was approximately 20 percent.
      Hospital volume was associated with a small decrease in complications (OR, 0.99;
      95 percent CI, 0.99 to 0.99; p < 0.01). For surgeons, years of experience and not
      annual case volume decreased surgical complications (OR, 0.98; 95 percent CI,
      0.97 to 0.99; p = 0.01). The authors did not find any association between
      hospital or surgeon volume, or surgeon's years of experience and 30-day
      rehospitalization. CONCLUSIONS: Higher-volume hospitals and more experienced
      surgeons were shown to have a lower likelihood of postsurgery complications.
      Hospital process and structure affect outcomes and reduce surgical complications.
      Reducing 30-day rehospitalization may require payment reform, as it demands
      coordinated care before and after hospital discharge. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, III.

PMID- 28746291
TI  - State of the Plastic Surgery Workforce and the Impact of Graduate Medical
      Education Reform on Training of Plastic Surgeons.
AB  - BACKGROUND: Although recent estimates predict a large impending shortage of
      plastic surgeons, graduate medical education funding through the Centers for
      Medicare and Medicaid Services remains capped by the 1997 Balanced Budget Act.
      The authors' aim was to develop a plan to stimulate legislative action. METHODS:
      The authors reviewed responses of the American Society of Plastic Surgeons,
      American College of Surgeons, and American Medical Association from January of
      2015 to a House Energy & Commerce Committee request for input on graduate medical
      education funding. In addition, all program directors in plastic surgery were
      surveyed through the American Council of Academic Plastic Surgeons to determine
      their graduate medical education funding sources. RESULTS: All three
      organizations agree that current graduate medical education funding is inadequate
      to meet workforce needs, and this has a significant impact on specialty selection
      and distribution for residency training. All agreed that funding should be tied
      to the resident rather than to the institution, but disagreed on whether funds
      should be divided between direct (allocated to residency training) and indirect
      (allocated to patient care) pools, as is currently practiced. Program directors'
      survey responses indicated that only 38 percent of graduate medical education
      funds comes from the Centers for Medicare and Medicaid Services. CONCLUSIONS:
      Organized medicine is at risk of losing critically needed graduate medical
      education funding. Specific legislation to support additional graduate medical
      education positions and funding (House Resolutions 1180 and 4282) has been
      proposed but has not been universally endorsed, in part because of a lack of
      collaboration in organized medicine. Collaboration among major organizations can
      reinvigorate these measures and implement real change in funding.

PMID- 28746292
TI  - Discussion: State of the Plastic Surgery Workforce and the Impact of Graduate
      Medical Education Reform on Training of Plastic Surgeons.

PMID- 28746294
TI  - The Indian Nose.

PMID- 28746295
TI  - Reply: The Indian Nose.

PMID- 28746296
TI  - Reply: Hemodynamic Study of Three Patterns of Flaps on Rats with a Novel
      Panoramic Photographing Technique Involved.

PMID- 28746297
TI  - Alveolar Bone Grafting and Cleft Lip and Palate: A Review.

PMID- 28746298
TI  - Reply: Alveolar Bone Grafting and Cleft Lip and Palate: A Review.

PMID- 28746299
TI  - The Importance of Patient Satisfaction: A Blessing, a Curse, or Simply
      Irrelevant?

PMID- 28746300
TI  - Reply: The Importance of Patient Satisfaction: A Blessing, a Curse, or Simply
      Irrelevant?

PMID- 28746301
TI  - Drugs for epilepsy.

PMID- 28746302
TI  - Comparison table: some oral antiepileptic drugs.

PMID- 28746303
TI  - Clinical Significance and Prognostic Implications of Quantifying Pulmonary
      Contusion Volume in Patients with Blunt Chest Trauma.
AB  - BACKGROUND Pulmonary contusion (PC) is the most frequent blunt chest injury which
      could be used to identify patients at high-risk of clinical deterioration. We
      aimed to investigate the clinical correlation between PC volume and outcome in
      patients with blunt chest trauma (BCT). MATERIAL AND METHODS BCT patients with PC
      were identified retrospectively from the prospectively collected trauma registry
      database over a 2-year period. Contusion volume was measured and expressed as
      percentage of total lung (CTCV) volume using three-dimensional reconstruction of
      thoracic CT images on admission. Data included patients' demographics, mechanism
      of injury (MOI) and injury severity, associated injuries, CTCV, mechanical
      ventilation, complications, and mortality. RESULTS A total of 226 BCT patients
      were identified to have PC with a mean age of 35.2 years. Motor vehicle crash
      (54.4%) and falls (16.4%) were the most frequent MOIs. Bilateral PC (61.5%) was
      more prevalent than right-sided (19.5%) and left-sided PC (19%). CTCV had a
      significant positive correlation with ISS; whereas, age and PaO2/FiO2 ratio
      showed a negative correlation (p<0.05 for all). The median CTCV was significantly
      higher in patients who developed in-hospital complications (p=0.02). A CTCV >20%
      was associated with increasedrisk of acute respiratory distress syndrome (ARDS),
      blood transfusion and prolonged mechanical ventilation. However, multiple linear
      regression analysis showed that CTCV alone was not an independent predictor of in
      hospital outcomes. Presence of chest infection, CTCV, and Injury Severity Scores
      were predictors of ARDS. CONCLUSIONS Quantifying pulmonary contusion volume could
      allow identification of patients at high-risk of ARDS. CTCV has a significant
      correlation with injury severity in patients with BCT. Further prospective
      studies are needed to address the validity of CTCV in the patients care.

PMID- 28746304
TI  - Complex cellular logic computation using ribocomputing devices.
AB  - Synthetic biology aims to develop engineering-driven approaches to the
      programming of cellular functions that could yield transformative technologies.
      Synthetic gene circuits that combine DNA, protein, and RNA components have
      demonstrated a range of functions such as bistability, oscillation, feedback, and
      logic capabilities. However, it remains challenging to scale up these circuits
      owing to the limited number of designable, orthogonal, high-performance parts,
      the empirical and often tedious composition rules, and the requirements for
      substantial resources for encoding and operation. Here, we report a strategy for
      constructing RNA-only nanodevices to evaluate complex logic in living cells. Our
      'ribocomputing' systems are composed of de-novo-designed parts and operate
      through predictable and designable base-pairing rules, allowing the effective in
      silico design of computing devices with prescribed configurations and functions
      in complex cellular environments. These devices operate at the post
      transcriptional level and use an extended RNA transcript to co-localize all
      circuit sensing, computation, signal transduction, and output elements in the
      same self-assembled molecular complex, which reduces diffusion-mediated signal
      losses, lowers metabolic cost, and improves circuit reliability. We demonstrate
      that ribocomputing devices in Escherichia coli can evaluate two-input logic with
      a dynamic range up to 900-fold and scale them to four-input AND, six-input OR,
      and a complex 12-input expression (A1 AND A2 AND NOT A1*) OR (B1 AND B2 AND NOT
      B2*) OR (C1 AND C2) OR (D1 AND D2) OR (E1 AND E2). Successful operation of
      ribocomputing devices based on programmable RNA interactions suggests that
      systems employing the same design principles could be implemented in other host
      organisms or in extracellular settings.

PMID- 28746305
TI  - Stimulation of functional neuronal regeneration from Muller glia in adult mice.
AB  - Many retinal diseases lead to the loss of retinal neurons and cause visual
      impairment. The adult mammalian retina has little capacity for regeneration. By
      contrast, teleost fish functionally regenerate their retina following injury, and
      Muller glia (MG) are the source of regenerated neurons. The proneural
      transcription factor Ascl1 is upregulated in MG after retinal damage in zebrafish
      and is necessary for regeneration. Although Ascl1 is not expressed in mammalian
      MG after injury, forced expression of Ascl1 in mouse MG induces a neurogenic
      state in vitro and in vivo after NMDA (N-methyl-d-aspartate) damage in young
      mice. However, by postnatal day 16, mouse MG lose neurogenic capacity, despite
      Ascl1 overexpression. Loss of neurogenic capacity in mature MG is accompanied by
      reduced chromatin accessibility, suggesting that epigenetic factors limit
      regeneration. Here we show that MG-specific overexpression of Ascl1, together
      with a histone deacetylase inhibitor, enables adult mice to generate neurons from
      MG after retinal injury. The MG-derived neurons express markers of inner retinal
      neurons, synapse with host retinal neurons, and respond to light. Using an assay
      for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq),
      we show that the histone deacetylase inhibitor promotes accessibility at key gene
      loci in the MG, and allows more effective reprogramming. Our results thus provide
      a new approach for the treatment of blinding retinal diseases.

PMID- 28746306
TI  - In vivo FRET-FLIM reveals cell-type-specific protein interactions in Arabidopsis
      roots.
AB  - During multicellular development, specification of distinct cell fates is often
      regulated by the same transcription factors operating differently in distinct cis
      regulatory modules, either through different protein complexes, conformational
      modification of protein complexes, or combinations of both. Direct visualization
      of different transcription factor complex states guiding specific gene expression
      programs has been challenging. Here we use in vivo FRET-FLIM (Forster resonance
      energy transfer measured by fluorescence lifetime microscopy) to reveal spatial
      partitioning of protein interactions in relation to specification of cell fate.
      We show that, in Arabidopsis roots, three fully functional fluorescently tagged
      cell fate regulators establish cell-type-specific interactions at endogenous
      expression levels and can form higher order complexes. We reveal that cell-type
      specific in vivo FRET-FLIM distributions reflect conformational changes of these
      complexes to differentially regulate target genes and specify distinct cell
      fates.

PMID- 28746307
TI  - Higher-order interactions stabilize dynamics in competitive network models.
AB  - Ecologists have long sought a way to explain how the remarkable biodiversity
      observed in nature is maintained. On the one hand, simple models of interacting
      competitors cannot produce the stable persistence of very large ecological
      communities. On the other hand, neutral models, in which species do not interact
      and diversity is maintained by immigration and speciation, yield unrealistically
      small fluctuations in population abundance, and a strong positive correlation
      between a species' abundance and its age, contrary to empirical evidence. Models
      allowing for the robust persistence of large communities of interacting
      competitors are lacking. Here we show that very diverse communities could persist
      thanks to the stabilizing role of higher-order interactions, in which the
      presence of a species influences the interaction between other species. Although
      higher-order interactions have been studied for decades, their role in shaping
      ecological communities is still unclear. The inclusion of higher-order
      interactions in competitive network models stabilizes dynamics, making species
      coexistence robust to the perturbation of both population abundance and parameter
      values. We show that higher-order interactions have strong effects in models of
      closed ecological communities, as well as of open communities in which new
      species are constantly introduced. In our framework, higher-order interactions
      are completely defined by pairwise interactions, facilitating empirical
      parameterization and validation of our models.

PMID- 28746308
TI  - Derivation of ground-state female ES cells maintaining gamete-derived DNA
      methylation.
AB  - Inhibitors of Mek1/2 and Gsk3beta, known as 2i, enhance the derivation of
      embryonic stem (ES) cells and promote ground-state pluripotency in rodents. Here
      we show that the derivation of female mouse ES cells in the presence of 2i and
      leukaemia inhibitory factor (2i/L ES cells) results in a widespread loss of DNA
      methylation, including a massive erasure of genomic imprints. Despite this global
      loss of DNA methylation, early-passage 2i/L ES cells efficiently differentiate
      into somatic cells, and this process requires genome-wide de novo DNA
      methylation. However, the majority of imprinting control regions (ICRs) remain
      unmethylated in 2i/L-ES-cell-derived differentiated cells. Consistently, 2i/L ES
      cells exhibit impaired autonomous embryonic and placental development by
      tetraploid embryo complementation or nuclear transplantation. We identified the
      derivation conditions of female ES cells that display 2i/L-ES-cell-like
      transcriptional signatures while preserving gamete-derived DNA methylation and
      autonomous developmental potential. Upon prolonged culture, however, female ES
      cells exhibited ICR demethylation regardless of culture conditions. Our results
      provide insights into the derivation of female ES cells reminiscent of the inner
      cell mass of preimplantation embryos.

PMID- 28746309
TI  - Ecology: Contests between species aid biodiversity.

PMID- 28746310
TI  - Hypothalamic stem cells control ageing speed partly through exosomal miRNAs.
AB  - It has been proposed that the hypothalamus helps to control ageing, but the
      mechanisms responsible remain unclear. Here we develop several mouse models in
      which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are
      ablated, as we observed that ageing in mice started with a substantial loss of
      these hypothalamic cells. Each mouse model consistently displayed acceleration of
      ageing-like physiological changes or a shortened lifespan. Conversely, ageing
      retardation and lifespan extension were achieved in mid-aged mice that were
      locally implanted with healthy hypothalamic stem/progenitor cells that had been
      genetically engineered to survive in the ageing-related hypothalamic inflammatory
      microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed
      greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these
      exosomal miRNAs declined during ageing, whereas central treatment with healthy
      hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing.
      In conclusion, ageing speed is substantially controlled by hypothalamic stem
      cells, partially through the release of exosomal miRNAs.

PMID- 28746311
TI  - Prolonged Mek1/2 suppression impairs the developmental potential of embryonic
      stem cells.
AB  - Concomitant activation of the Wnt pathway and suppression of Mapk signalling by
      two small molecule inhibitors (2i) in the presence of leukaemia inhibitory factor
      (LIF) (hereafter termed 2i/L) induces a naive state in mouse embryonic stem (ES)
      cells that resembles the inner cell mass (ICM) of the pre-implantation embryo.
      Since the ICM exists only transiently in vivo, it remains unclear how sustained
      propagation of naive ES cells in vitro affects their stability and functionality.
      Here we show that prolonged culture of male mouse ES cells in 2i/L results in
      irreversible epigenetic and genomic changes that impair their developmental
      potential. Furthermore, we find that female ES cells cultured in conventional
      serum plus LIF medium phenocopy male ES cells cultured in 2i/L. Mechanistically,
      we demonstrate that the inhibition of Mek1/2 is predominantly responsible for
      these effects, in part through the downregulation of DNA methyltransferases and
      their cofactors. Finally, we show that replacement of the Mek1/2 inhibitor with a
      Src inhibitor preserves the epigenetic and genomic integrity as well as the
      developmental potential of ES cells. Taken together, our data suggest that,
      although short-term suppression of Mek1/2 in ES cells helps to maintain an ICM
      like epigenetic state, prolonged suppression results in irreversible changes that
      compromise their developmental potential.

PMID- 28746313
TI  - Stem cells: The cost of perpetual youth.

PMID- 28746314
TI  - Outcome of Endoscopic Variceal Band Ligation.
AB  - INTRODUCTION: Bleeding from esophageal varices in cirrhosis is an emergent
      condition with high mortality. One of the preferred modality of treating
      esophageal varices is EVL. We aimed to find out the outcome of EVL in controlling
      acute esophageal variceal bleeding, prophylactic banding to prevent future
      bleeding and the number of sessions required for complete eradication of varices.
      METHODS: This descriptive observational study was carried out in Gastroenterology
      and Hepatology unit of Bir Hospital, NAMS from June 2016 to May 2017. Consecutive
      cases who presented in emergency room with acute variceal bleeding due to liver
      cirrhosis and cases of liver cirrhosis with large varices and red color signs on
      endoscopic examination were enrolled. They underwent EVL and subsequent re
      endoscope at one month interval till the eradication of varices was achieved.
      RESULTS: Among 83 patients, 15 (18.1%) were of Child Pugh class A, 29 (34.9%) B
      and 39 (47%) were of C. In 20 (24.1%) cases varices could be eradicated in one
      session of EVL while 57 (68.7%) required two sessions and in 6 (7.2%) cases it
      took three sessions. Total average EVL session required for obliteration of
      esophageal varices was 1.84+/-0.53. There was only one (1.2%) of early re
      bleeding post EVL. CONCLUSIONS: EVL is an effective modality of treatment in
      controlling acute esophageal variceal bleeding, in preventing future variceal
      bleeding as well as in eradicating esophageal varices with very few
      complications.

PMID- 28746312
TI  - Sequencing and de novo assembly of 150 genomes from Denmark as a population
      reference.
AB  - Hundreds of thousands of human genomes are now being sequenced to characterize
      genetic variation and use this information to augment association mapping studies
      of complex disorders and other phenotypic traits. Genetic variation is identified
      mainly by mapping short reads to the reference genome or by performing local
      assembly. However, these approaches are biased against discovery of structural
      variants and variation in the more complex parts of the genome. Hence, large
      scale de novo assembly is needed. Here we show that it is possible to construct
      excellent de novo assemblies from high-coverage sequencing with mate-pair
      libraries extending up to 20 kilobases. We report de novo assemblies of 150
      individuals (50 trios) from the GenomeDenmark project. The quality of these
      assemblies is similar to those obtained using the more expensive long-read
      technology. We use the assemblies to identify a rich set of structural variants
      including many novel insertions and demonstrate how this variant catalogue
      enables further deciphering of known association mapping signals. We leverage the
      assemblies to provide 100 completely resolved major histocompatibility complex
      haplotypes and to resolve major parts of the Y chromosome. Our study provides a
      regional reference genome that we expect will improve the power of future
      association mapping studies and hence pave the way for precision medicine
      initiatives, which now are being launched in many countries including Denmark.

PMID- 28746315
TI  - Colorectal Cancer in Different Age Groups in a Tertiary Hospital in Nepal.
AB  - INTRODUCTION: Some studies have suggested that colorectal cancer at a younger age
      had distinct biological characteristics: different clinical presentations, more
      advanced stage at time of diagnosis and poorly differentiated carcinoma. The aim
      of the study is to analyze clinical and histopathological differences between
      younger (<=40 years of age) and older (>40 years of age) colorectal cancer
      patients. METHODS: A cross-sectional analysis was conducted amongst the
      colorectal cancer patients who visited Bir Hospital between July 2015 and April
      2017. All colonoscopically diagnosed and histopathologically proven cases of
      colon cancer were included. Chi-square test and independent t - test was
      performed to analyze the difference between clinical presentations and
      histopathological findings among two groups of patients and P value of <0.05 was
      considered as significant. RESULTS: Thirty younger patients and thirty older
      patients were enrolled without any differences in gender proportion. There were
      no statistical differences between clinical presentation and histological grade
      and type in younger and older patients. The younger patients had more complaints
      of altered bowel habit (P <0.001) while older patients mostly presented with per
      rectal bleeding (P< 0.008). CONCLUSIONS: In this study, colorectal cancer at
      younger ages showed similar characteristics to those of older patients except
      altered bowel habit was more common in younger patients while per rectal bleeding
      was more common in older patients. Although colorectal cancer incidence increases
      with age, younger patients with altered bowel habits, weight loss, anemia and
      anorexia should also be given due medical attention and undergo evaluation
      promptly.

PMID- 28746316
TI  - Efficacy of Prophylactic use of Ciprofloxacin and Metronidazole in Mild and
      Moderately Severe Acute Pancreatitis.
AB  - INTRODUCTION: There are new concepts and developments in the diagnosis and
      management of acute pancreatitis. Current evidence suggests that there is no role
      of prophylactic antibiotics use in acute pancreatitis. However, it is still a
      common practice to administer prophylactic antibiotics in a country like Nepal.
      So, we have conducted a study in mild and moderately severe acute pancreatitis to
      study the efficacy of prophylactic antibiotics. METHODS: A case control study was
      conducted among 76 patients comparing efficacy of prophylactic antibiotics versus
      no antibiotics in patients with mild and moderately severe acute pancreatitis.
      RESULTS: The two most common etiology of acute pancreatitis in AG and NAG were
      alcohol 21 (55.2%) vs. 24 (63.1%) and biliary 10 (26.3%) vs. 4 (10.5%)
      respectively. Pancreatic necrosis was seen in five (13.1 %) in AG and four
      (10.5%) in NAG. Four (10.5%) developed extra pancreatic complications in AG and
      five (13.1%) in NAG. There was one (2.6%) death in AG and no death in NAG.
      Abdominal pain improvement seen in AG vs. NAG was 3.2 days vs. 2.4 days
      (P=0.002). The hospital stay was 7.7+/-2.23 days in AG and 7.5+/-1.85 days in NAG
      (P=0.65). CONCLUSIONS: The routine use of prophylactic antibiotics for mild and
      moderately severe acute pancreatitis is not associated with improvement in
      meaningful clinical outcomes.

PMID- 28746317
TI  - Acute Upper Gastrointestinal Bleeding in a Tertiary Care Centre of Nepal.
AB  - INTRODUCTION: AUGIB is characterized by hematemesis or melena or both. Peptic
      ulcers and variceal bleed account for majority of cases. Use of proton pump
      inhibitors in current era is associated with a gradual reduction in burden of
      peptic ulcer disease. We conducted this study to look into the cause of AUGIB in
      our community. METHODS: We studied 100 patients in one year period who presented
      to us with hematemesis or melena. The study was conducted in department of
      Gastroenterology, Bir hospital, Kathmandu. We identified the culprit lesions by
      upper gastrointestinal endoscopy. RESULTS: The average age of patients with AUGIB
      was 51.6 years with 59 (59%) males. Duodenal ulcers are most common 29 (29%),
      followed by varices 23 (23%) and gastric ulcers 14 (14%). More than one lesion
      was identified in 38 (38%) patients. Patients with variceal bleed were more
      likely to present with hematemesis alone as compared to those with ulcer bleed
      (P=0.005). Variceal bleed patients presented earlier to the hospital (P=0.005),
      had lower MAP at presentation (P=0.0002), had lower hemoglobin level (P=0.0001)
      and higher serum creatinine level at presentation (P=0.001). Patients with
      variceal bleed were more likely to have consumed alcohol 20 (86.9%) and patients
      with ulcer bleed were more likely to be smokers 29 (67.4%) or consume tobacco 14
      (32.5%) (P=0.006). CONCLUSIONS: Ulcer related bleeding is still the most common
      cause of AUGIB. Many patients with AUGIB have more than one lesions identified
      during upper gastrointestinal endoscopy.

PMID- 28746318
TI  - Correlation of Visual Prostate Symptom Score with International Prostate Symptom
      Score and Uroflowmetry Parameters in Nepalese Male Patients with Lower Urinary
      Tract Symptoms.
AB  - INTRODUCTION: International prostate symptom score is a validated questionnaire
      used to evaluate the lower urinary tract symptoms in benign prostatic
      hyperplasia. Visual prostate symptom score is a new simplified symptom score with
      pictograms to evaluate the same. We evaluated the correlation of visual prostate
      symptom score with international prostate symptom score and uroflowmetry
      parameters in Nepalese male patients with lower urinary tract symptoms. METHODS:
      Male patients aged >=40 years attending the Urology clinic were enrolled in the
      study. They were given international prostate symptom score and visual prostate
      symptom score questionnaires to complete providing assistance whenever needed.
      Demographic data, examination findings and uroflowmetry parameters were noted.
      Correlation and regression analysis was used to identify correlation of the two
      scoring systems and uroflowmetry parameters. RESULTS: Among the 66 patients
      enrolled, only 10 (15.15%) patients were able to understand English language.
      There was a statistically significant correlation between total visual prostate
      symptom score and international prostate symptom score (r= 0.822; P<0.01). The
      correlations between individual scores of the two scoring systems related to
      force of urinary stream, frequency, nocturia and quality of life were also
      statistically significant. There was also a statistically significant correlation
      of both scores with maximum flow rate and average flow rate. CONCLUSIONS: There
      is a statistically significant correlation of visual prostate symptom score with
      international prostate symptom score and uroflowmetry parameters. IPSS can be
      replaced with simple VPSS in evaluation of lower urinary tract symptoms in
      elderly male patients.

PMID- 28746319
TI  - Systemic Inflammatory Response Syndrome following Gastrointestinal Surgery.
AB  - INTRODUCTION: Systemic inflammatory response syndrome symptoms immediately after
      surgery have lately been regarded as potential warnings of impending post
      operative complications and multiple organ failure. This study was conducted to
      find out the clinical significance of systemic inflammatory response syndrome in
      postoperative patients and to investigate the relationship between the duration
      of post-operative systemic inflammatory response syndrome and the post-operative
      morbidity and mortality. METHODS: Total 30 patients who received different
      gastrointestinal surgery and fulfilled the diagnostic criteria for systemic
      inflammatory response syndrome between 2006 and 2008 at Kathmandu Medical College
      Teaching Hospital were included. Patients were analyzed for preoperative
      physiologic status, surgical stress parameters, and postoperative status of
      systemic inflammatory response syndrome, complications, and end-organ
      dysfunction. RESULTS: Duration of systemic inflammatory response syndrome or
      positive criteria's number of systemic inflammatory response syndrome after
      surgery significantly correlated with surgical stress parameters (blood loss/body
      weight and operation time). Septic complications and prolongation of systemic
      inflammatory response syndrome were associated with multiple organ dysfunction
      syndrome and increased mortality. CONCLUSIONS: Systemic inflammatory response
      syndrome is a useful criterion for the recognition of postoperative complications
      and end-organ dysfunctions. Early recovery from systemic inflammatory response
      syndrome may arrest the progression of organ dysfunction, thus reducing the
      mortality.

PMID- 28746320
TI  - C-reactive Protein in Periodontitis and its Comparison with Body Mass Index and
      Smoking Behaviour.
AB  - INTRODUCTION: Chronic periodontitis is an infectious disease resulting in
      inflammation within the supporting tissues of the teeth, progressive attachment
      loss, and bone loss. In addition to declining oral health, there is always low
      grade infection present in periodontitis. Studies show increased levels of
      systemic biomarkers in periodontal disease such as CRP, which is considered a key
      marker of CVD. Research has also shown positive association between BMI and
      smoking with periodontitis and CRP. The objective of the study was to assess the
      levels of CRP in patients with and without periodontitis and their relation with
      BMI and smoking behaviour. METHODS: Patients visiting the Dental department of
      Bir Hospital were invited to participate in the study. Total 31 subjects in each
      group: Case (periodontitis) and Control (without periodontitis) were selected
      using convenience sampling technique. All subjects underwent periodontal
      examination by a single examiner. Serum CRP samples were taken before periodontal
      treatment. Data analysis was done by SPSS 17 software program. RESULTS: Increase
      in mean CRP levels in periodontitis (5.8595mg/L) with high statistical
      significance (P=0.000) in comparison to subjects without periodontitis
      (1.1214mg/L) was observed. BMI showed positive association with periodontitis
      (P=0.046) but not with CRP (0.213). Smoking behaviour showed no significant
      relation with either CRP (P=0.344) or periodontitis (P=0.541). CONCLUSIONS: We
      found highly significant association between periodontitis and CRP levels but not
      always with BMI and smoking. CRP, which is an established marker for CVD was
      significantly increased in periodontal infections. Hence, a close interaction
      among Physician, Periodontist and Patient to prevent adverse health situations is
      recommended.

PMID- 28746321
TI  - Scleral Fixation of Intraocular Lens with Ab Interno Technique.
AB  - INTRODUCTION: Implantation of scleral fixation intraocular lens for the surgical
      management of aphakia cases without capsular support is a safe procedure.
      METHODS: Prospective study was carried out at Lumbini Eye Institute, Bhairahawa.
      A total of 32 patients underwent scleral fixation intraocular lens implantation
      within a period of two years from February 2014 to February 2016. RESULTS: The
      age range was from 15 to 79 years; mean age was 47.56 +/- 20.16 SD. Among them 14
      (43.75%) were male and 18 (56.25%) were female. The follow-up lasted for 24
      months. CONCLUSIONS: SFIOL for the surgical management of aphakia in the absence
      of capsular support is a safe procedure. The long-term follow-up is needed for an
      accurate evaluation of outcomes.

PMID- 28746322
TI  - Approximation of Height of an Individual Using Somatometry of Human Male Skull.
AB  - INTRODUCTION: Numerous population specific studies conducted on skeletal remains
      have aimed to standardize the identification process. Known for ethnic and sexual
      variations, skull bone can also assist the identification process by estimating
      stature of the individual. The present study focuses on estimation of stature
      from skull bone using uni-variate and multi-variate regression models in south
      Indian population. METHODS: Stature and maximum cranial length, maximum cranial
      breadth, bi-pterion breadth, parietal cord and upper facial breadth were measured
      in wet skulls of 113 males, autopsied at Government Hospital of Kudla, Karnataka.
      RESULTS: All five measurements showed significant correlation with stature (P
      value <0.001). MCL showed the highest (r=0.77) and UFB the lowest (r=0.42) degree
      of correlation. Standard error of estimate was lowest for MCL (4.90 cm) in the
      derived uni-variate regression models. In the regression model obtained from the
      multi-variate analysis using all five skull measurements the beta-coefficients
      were significant (P value <0.001) and the Standard Error of Estimation of the
      model was observed to be 4.45 cm. Bland-Altman analysis was conducted to explore
      the agreement between the actual length and the estimated lengths from the
      multivariate regression model. The mean of difference was 0.105 with a standard
      deviation of 4.3 and the upper and lower limits of agreement were 8.5 and -8.3
      respectively. CONCLUSIONS: The study concludes that stature can be estimated from
      skull measurements with reasonable accuracy, observations of multi-variate
      regression models being more precise than the uni-variate regression models. Data
      collected from South India was compared with data available for Nepalese
      population and validates the use of data of Indian population for extrapolation
      in Nepalese population.

PMID- 28746323
TI  - Ocular Morbidity among Children of Government Schools of Kathmandu Valley: A
      Follow-up Study.
AB  - INTRODUCTION: Ocular and vision defects are common among school going children.
      Vision disorders, especially refractive errors are the main disabilities of
      children and the leading cause of handicapping conditions of childhood. The
      present study was conducted to find out ocular morbidity among students of
      government schools of Kathmandu valley. METHODS: In the descriptive and cross
      sectional study, 2412 students, comprising of 1114 (46.2%) males and 1298 (53.8%)
      females were enrolled in to the study from the five government schools of
      Kathmandu valley from 2012 to 2013. Detailed eye examination included distance
      visual acuity testing, anterior and posterior segment examinations, retinoscopy
      and refraction, cover test, near point of convergence, amplitude of accommodation
      and color vision test. The Chi-square test was performed to analyze the
      association between ocular morbidity, age and sex. P value was considered
      significant at 0.05 for 95% confidence interval. RESULTS: Majority of children
      were age group between 11 and 13 years (n= 783, 32.5%). A male to female ratio
      was 0.85. Presenting and best spectacle corrected visual acuity of 6/6 was
      present in 2257 (93.6%) and 2380 (98.7%) respectively. Total ocular morbidity was
      observed in 515 (21.4%) subjects. The most common types of ocular morbidity were
      refractive error in 241 (10%), conjunctivitis in 104 (4.3%) and convergence
      insufficiency in 82 (3.4%). CONCLUSIONS: Refractive error, conjunctivitis and
      convergence insufficiency represent the most common ocular morbidities among
      students of government schools.

PMID- 28746324
TI  - Assessment of Automatic Thoughts in Patients with Depressive Illness at a
      Tertiary Hospital in Nepal.
AB  - INTRODUCTION: Cognitive functions have significant influence on psycho-social and
      general wellbeing. The quality, content and processing of negative thoughts
      initiate depressive symptoms; i.e. low mood, decreased self-worth and diminished
      interest in pleasurable activities. The study assessed the automatic thoughts of
      patients having depressive illness and evaluated and compared the changes after
      therapy; i.e. Psychotherapy and pharmacotherapy. METHODS: Diagnosed cases of
      depressive illness (n=135), according to ICD-10 and study criteria, attending the
      out-patient clinic of Department of Psychiatry and Mental Health, Tribhuvan
      University Teaching Hospital, were included. Beck Depression Inventory was used
      to screen level of depressive symptoms. Automatic thoughts were assessed by the
      Automatic Thought Questionnaire-Revised before initiating therapy and after
      completion of therapy for comparison. Depressive patients received either of the
      three treatment procedures after randomization of the study sample into three
      different treatment groups; i.e. Cognitive behavior therapy, pharmacotherapy or
      combined therapy receiving both cognitive behavior therapy and pharmacotherapy.
      RESULTS: Among the total 135 patients, 53 (39.3%) had moderate, 47 (34.8%) had
      severe depressive and 35 (25.9%) had mild depressive symptoms before therapeutic
      interventions. Negative automatic thoughts were significantly present in
      depressed patients and reduced after all three interventions. Negative automatic
      thoughts of hopelessness, anxiety and inability coping were significantly reduced
      after therapy. CONCLUSIONS: Automatic negative thoughts were significantly
      correlated with depressive disorder. Combined therapy CBT with pharmacotherapy or
      CBT alone was found to be more effective in modifying automatic negative thoughts
      than pharmacotherapy alone, ultimately reducing depressive symptoms to a
      significant degree.

PMID- 28746325
TI  - Effect of Maternal Socio-demographic Factors and Child Feeding Practice on
      Wasting Among Under Five Years Children in Slum Area of Rupandehi District in
      Nepal.
AB  - INTRODUCTION: Childhood wasting although well studied elsewhere, it has not been
      well understood about in slum area of Nepal. This study aimed to assess effect of
      socio-demographic factors and child feeding practice in the determination of
      wasting among the children under five years of age in slum area of Nepal.
      METHODS: A community based cross-sectional study was performed among 150 children
      under five years of age from the slum area of Nepal between 1st January and 28th
      February 2013 using simple random sampling techniques. Multivariate analyses were
      performed to determine factors associated with wasting controlling the potential
      confounders. RESULTS: In a total of 150 under five years children, the prevalence
      of wasting was 56 (37.33%). The current study demonstrated that children of
      mothers from dalit Adjusted Odds Ratio (OR) 11.5; 95% CI: 03.1 - 41.3),
      aadibasi/janajati (AOR 4.6; 95% CI: 1.2 - 17.0), illiterate mothers (AOR 3.6; 95%
      CI: 1.1 - 13.6), laborer mothers (AOR 2.1; 95% CI: 1.1-9.4), child age group 25
      36 months (AOR 2.8; 95% CI: 1.5-5.3), multiple child birth order (AOR 10.0; 95%
      CI: 2.5-25.0), children who were not fed colostrums (AOR 15.0; 95% CI: 1.25-10.0)
      were more likely to develop wasting compared to their counterparts. CONCLUSIONS:
      As incremental childhood wasting is associated with maternal socio-demographic
      factors and child feeding practice, health promotion strategies should focus
      maternal socio-demographic factors, age of children and early initiation of
      breast feeding for the improved child nutrition in slum area of Nepal.

PMID- 28746326
TI  - Giant Sialolith of Submandibular Duct.
AB  - Sialolithiasis is one of the most common diseases of salivary glands and commonly
      involves submandibular gland and ducts. "Giant sialoliths" typically measure more
      than 15 mm in any dimension. Here, an unusual case of sialolith in submandibular
      duct is reported which progressed into a giant sialolith in six months' time is
      reported. A 42-year-old man presented with complaints of recurrent pain and
      swelling in the right submandibular area. A large stone was palpable intraorally
      within the Wharton's duct and intra-operatively, an elongated giant sialolith of
      50 mm length was found which is the second largest to be published till date.

PMID- 28746327
TI  - Regional Anaesthesia in Clavicle Surgery.
AB  - In routine practice, regional anaesthesia is less commonly used for clavicular
      fracture compared to general anaesthesia. We report two cases of clavicle
      fracture for which operative treatment was done under combined superficial
      cervical plexus and interscalene brachial plexus block. In both the cases
      combination of ropivacaine and dexmeditomidine was used for block. Both the
      patients exhibited comfort and there was no additional analgesic demand in both
      the cases. Thus combination of interscalene and superficial cervical plexus block
      can prove to be useful in patients with clavicle fracture where administration of
      general anaesthesia and its adverse effects could be avoided.

PMID- 28746328
TI  - Unresolving Pneumonia with Pleural effusion: Pulmonary Paragonimiasis.
AB  - Paragonimiasis is a zoonosis caused by many species of Paragonimus commonly P.
      westermani. Human get infected by eating raw, salted, pickled, smoked, partially
      cooked crustaceans (crayfish or crabs). Clinical manifestations ranges from non
      specific symptoms like pain abdomen, diarrhea, urticarial rashes, fever to
      pleuropulmonary symptoms like cough, hemoptysis, chest pain and dyspnea. A 48
      years, female presented at TUTH emergency with fever on and off for nine months,
      cough and shortness of breath for three months, lethargy, malaise and urticaria
      with history of raw crab intake one month prior to the onset of symptoms. Blood
      and pleural fluid analysis revealed raised total counts with eosinophilia and x
      ray showed bilateral infiltration of lower lobes with pleural effusion. Diagnosis
      was confirmed by microscopic examination of sputum for Paragonimus. She responded
      well to Praziquantel. Pulmonary paragonimiasis must be considered in the
      differential diagnosis of unresolving pneumonia and unexplained
      hypereosinophilia.

PMID- 28746329
TI  - Plasmablastic Lymphoma.
AB  - Plasmablastic lymphoma is a rare and aggressive lymphoma reported to be commonly
      associated with immunodeficiency state. It possesses a challenge to the clinician
      owing it aggressiveness and poor prognosis. No standard of care treatment is
      available for the disease. Here we report a case of an immunocompetant 67 years
      female who is unique in her presentation as she did not have any of the
      conventional clinical features and had a history of urothelial carcinoma three
      months back.

PMID- 28746330
TI  - Updates on Pharmacological Treatment of Post-Traumatic Stress Disorder.
AB  - Post-Traumatic Stress Disorder affects a significant proportion of those who have
      been exposed to exceptionally threatening or catastrophic events or situations
      such as earthquakes, rape and civil war. The condition can often become chronic
      and disabling. Medical intervention can therefore be of paramount importance.
      There are no national guidelines for trauma disorders in Nepal and there is a
      lack of adequate knowledge regarding drug treatment of PTSD among doctors and
      other service providers. Though psychotherapy is internationally regarded as the
      first line treatment for PTSD, it is often not feasible in Nepal due to lack of
      resources and skilled health workers in this field. The use of right psycho
      pharmacotherapy is therefore important to reduce the burden of disease. A wide
      range of pharmacotherapy has been tested in the treatment of PTSD. This article
      is based on a selected sample of relevant articles from PubMed, PsycINFO,
      national guidelines from other countries and our own clinical experience. We have
      tried to give a concise and practical review regarding the use of drugs, their
      side effects and available evidence in the treatment of PTSD. The main findings
      point to use of Selective Serotonin Reuptake Inhibitors as the first line
      pharmacotherapy, and they can have effect on the full range of symptoms in PTSD.
      SNRIs show similar efficacy. Adjuvant drugs like Alpha-blockers and atypical
      antipsychotics have shown strong evidence in treating partially remitted cases
      and resolving ancillary symptoms.

PMID- 28746331
TI  - Need of The Ministry of Health in Federal Democratic Republic of Nepal.
AB  - The constitution of Nepal provides appointing a council of ministers both at
      federal and provincial levels without defining portfolios. There is a political
      agreement that MOH will be retained at the federal level. This article draws
      evidences around the world to meet health needs of Nepalese, the role of
      provincial ministry of health and coordinating structure at district/local level.
      The constitution emphasises on health and pronounced in 46 articles which
      provides guidance for the creation of federalized governance levels at federal,
      provincial and local levels. Retaining ministry of health at federal level
      without creating devolved structure at province and local levels in health sector
      will create difficulty in translating the spirit of the constitution and may not
      be effective in addressing health issues nationally and meeting global
      achievements like SDGs. It is suggested to establish an elaborate health system
      accordingly in Nepal to ensure constitutional mandate of health as a basic human
      right.

PMID- 28746332
TI  - Proceeding Report of Joint Meeting of Nepalese Association for the Studies of the
      Liver and Nepalese Society of Gastroenterologists on Overcoming the Challenges
      for Hepatitis C Virus Elimination in Nepal by 2030.

PMID- 28746334
TI  - Transient dynamics in trial-offer markets with social influence: Trade-offs
      between appeal and quality.
AB  - We study a trial-offer market where consumers may purchase one of two competing
      products. Consumer preferences are affected by the products quality, their
      appeal, and their popularity. While the asymptotic convergence or stationary
      states of these, and related dynamical systems, has been vastly studied, the
      literature regarding the transitory dynamics remains surprisingly sparse. To fill
      this gap, we derive a system of Ordinary Differential Equations, which is solved
      exactly to gain insight into the roles played by product qualities and appeals in
      the market behavior. We observe a logarithmic tradeoff between quality and appeal
      for medium and long-term marketing strategies: The expected market shares remain
      constant if a decrease in quality is followed by an exponential increase in the
      product appeal. However, for short time horizons, the trade-off is linear.
      Finally, we study the variability of the dynamics through Monte Carlo simulations
      and discover that low appeals may result in high levels of variability. The model
      results suggest effective marketing strategies for short and long time horizons
      and emphasize the significance of advertising early in the market life to
      increase sales and predictability.

PMID- 28746333
TI  - Transmission dynamics of co-endemic Plasmodium vivax and P. falciparum in
      Ethiopia and prevalence of antimalarial resistant genotypes.
AB  - Ethiopia is one of the few African countries where Plasmodium vivax is co-endemic
      with P. falciparum. Malaria transmission is seasonal and transmission intensity
      varies mainly by landscape and climate. Although the recent emergence of drug
      resistant parasites presents a major issue to malaria control in Ethiopia, little
      is known about the transmission pathways of parasite species and prevalence of
      resistant markers. This study used microsatellites to determine population
      diversity and gene flow patterns of P. falciparum (N = 226) and P. vivax (N =
      205), as well as prevalence of drug resistant markers to infer the impact of gene
      flow and existing malaria treatment regimes. Plasmodium falciparum indicated a
      higher rate of polyclonal infections than P. vivax. Both species revealed
      moderate genetic diversity and similar population structure. Populations in the
      northern highlands were closely related to the eastern Rift Valley, but slightly
      distinct from the southern basin area. Gene flow via human migrations between the
      northern and eastern populations were frequent and mostly bidirectional.
      Landscape genetic analyses indicated that environmental heterogeneity and
      geographical distance did not constrain parasite gene flow. This may partly
      explain similar patterns of resistant marker prevalence. In P. falciparum, a high
      prevalence of mutant alleles was detected in codons related to chloroquine (pfcrt
      and pfmdr1) and sulfadoxine-pyrimethamine (pfdhps and pfdhfr) resistance. Over
      60% of the samples showed pfmdr1 duplications. Nevertheless, no mutation was
      detected in pfK13 that relates to artemisinin resistance. In P. vivax, while
      sequences of pvcrt-o were highly conserved and less than 5% of the samples showed
      pvmdr duplications, over 50% of the samples had pvmdr1 976F mutation. It remains
      to be tested if this mutation relates to chloroquine resistance. Monitoring the
      extent of malaria spread and markers of drug resistance is imperative to inform
      policy for evidence-based antimalarial choice and interventions. To effectively
      reduce malaria burden in Ethiopia, control efforts should focus on seasonal
      migrant populations.

PMID- 28746335
TI  - Adjudicating between face-coding models with individual-face fMRI responses.
AB  - The perceptual representation of individual faces is often explained with
      reference to a norm-based face space. In such spaces, individuals are encoded as
      vectors where identity is primarily conveyed by direction and distinctiveness by
      eccentricity. Here we measured human fMRI responses and psychophysical similarity
      judgments of individual face exemplars, which were generated as realistic 3D
      animations using a computer-graphics model. We developed and evaluated multiple
      neurobiologically plausible computational models, each of which predicts a
      representational distance matrix and a regional-mean activation profile for 24
      face stimuli. In the fusiform face area, a face-space coding model with sigmoidal
      ramp tuning provided a better account of the data than one based on exemplar
      tuning. However, an image-processing model with weighted banks of Gabor filters
      performed similarly. Accounting for the data required the inclusion of a
      measurement-level population averaging mechanism that approximates how fMRI
      voxels locally average distinct neuronal tunings. Our study demonstrates the
      importance of comparing multiple models and of modeling the measurement process
      in computational neuroimaging.

PMID- 28746336
TI  - Discovery of novel brain permeable and G protein-biased beta-1 adrenergic
      receptor partial agonists for the treatment of neurocognitive disorders.
AB  - The beta-1 adrenergic receptor (ADRB1) is a promising therapeutic target
      intrinsically involved in the cognitive deficits and pathological features
      associated with Alzheimer's disease (AD). Evidence indicates that ADRB1 plays an
      important role in regulating neuroinflammatory processes, and activation of ADRB1
      may produce neuroprotective effects in neuroinflammatory diseases. Novel small
      molecule modulators of ADRB1, engineered to be highly brain permeable and
      functionally selective for the G protein with partial agonistic activity, could
      have tremendous value both as pharmacological tools and potential lead molecules
      for further preclinical development. The present study describes our ongoing
      efforts toward the discovery of functionally selective partial agonists of ADRB1
      that have potential therapeutic value for AD and neuroinflammatory disorders,
      which has led to the identification of the molecule STD-101-D1. As a functionally
      selective agonist of ADRB1, STD-101-D1 produces partial agonistic activity on G
      protein signaling with an EC50 value in the low nanomolar range, but engages very
      little beta-arrestin recruitment compared to the unbiased agonist isoproterenol.
      STD-101-D1 also inhibits the tumor necrosis factor alpha (TNFalpha) response
      induced by lipopolysaccharide (LPS) both in vitro and in vivo, and shows high
      brain penetration. Other than the therapeutic role, this newly identified,
      functionally selective, partial agonist of ADRB1 is an invaluable research tool
      to study mechanisms of G protein-coupled receptor signal transduction.

PMID- 28746337
TI  - Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that
      genetic drift and soft selective sweeps contribute to loss of drug sensitivity.
AB  - BACKGROUND: Treatment of onchocerciasis using mass ivermectin administration has
      reduced morbidity and transmission throughout Africa and Central/South America.
      Mass drug administration is likely to exert selection pressure on parasites, and
      phenotypic and genetic changes in several Onchocerca volvulus populations from
      Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment
      have raised concern that sub-optimal responses to ivermectin's anti-fecundity
      effect are becoming more frequent and may spread. METHODOLOGY/PRINCIPAL FINDINGS:
      Pooled next generation sequencing (Pool-seq) was used to characterise genetic
      diversity within and between 108 adult female worms differing in ivermectin
      treatment history and response. Genome-wide analyses revealed genetic variation
      that significantly differentiated good responder (GR) and sub-optimal responder
      (SOR) parasites. These variants were not randomly distributed but clustered in
      ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position
      and gene content between the two countries. Published candidate ivermectin SOR
      genes were largely absent in these regions; QTLs differentiating GR and SOR worms
      were enriched for genes in molecular pathways associated with neurotransmission,
      development, and stress responses. Finally, single worm genotyping demonstrated
      that geographic isolation and genetic change over time (in the presence of drug
      exposure) had a significantly greater role in shaping genetic diversity than the
      evolution of SOR. CONCLUSIONS/SIGNIFICANCE: This study is one of the first genome
      wide association analyses in a parasitic nematode, and provides insight into the
      genomics of ivermectin response and population structure of O. volvulus. We argue
      that ivermectin response is a polygenically-determined quantitative trait (QT)
      whereby identical or related molecular pathways but not necessarily individual
      genes are likely to determine the extent of ivermectin response in different
      parasite populations. Furthermore, we propose that genetic drift rather than
      genetic selection of SOR is the underlying driver of population differentiation,
      which has significant implications for the emergence and potential spread of SOR
      within and between these parasite populations.

PMID- 28746339
TI  - OpenMM 7: Rapid development of high performance algorithms for molecular
      dynamics.
AB  - OpenMM is a molecular dynamics simulation toolkit with a unique focus on
      extensibility. It allows users to easily add new features, including forces with
      novel functional forms, new integration algorithms, and new simulation protocols.
      Those features automatically work on all supported hardware types (including both
      CPUs and GPUs) and perform well on all of them. In many cases they require
      minimal coding, just a mathematical description of the desired function. They
      also require no modification to OpenMM itself and can be distributed
      independently of OpenMM. This makes it an ideal tool for researchers developing
      new simulation methods, and also allows those new methods to be immediately
      available to the larger community.

PMID- 28746338
TI  - Detecting epistasis with the marginal epistasis test in genetic mapping studies
      of quantitative traits.
AB  - Epistasis, commonly defined as the interaction between multiple genes, is an
      important genetic component underlying phenotypic variation. Many statistical
      methods have been developed to model and identify epistatic interactions between
      genetic variants. However, because of the large combinatorial search space of
      interactions, most epistasis mapping methods face enormous computational
      challenges and often suffer from low statistical power due to multiple test
      correction. Here, we present a novel, alternative strategy for mapping epistasis:
      instead of directly identifying individual pairwise or higher-order interactions,
      we focus on mapping variants that have non-zero marginal epistatic effects-the
      combined pairwise interaction effects between a given variant and all other
      variants. By testing marginal epistatic effects, we can identify candidate
      variants that are involved in epistasis without the need to identify the exact
      partners with which the variants interact, thus potentially alleviating much of
      the statistical and computational burden associated with standard epistatic
      mapping procedures. Our method is based on a variance component model, and relies
      on a recently developed variance component estimation method for efficient
      parameter inference and p-value computation. We refer to our method as the
      "MArginal ePIstasis Test", or MAPIT. With simulations, we show how MAPIT can be
      used to estimate and test marginal epistatic effects, produce calibrated test
      statistics under the null, and facilitate the detection of pairwise epistatic
      interactions. We further illustrate the benefits of MAPIT in a QTL mapping study
      by analyzing the gene expression data of over 400 individuals from the GEUVADIS
      consortium.

PMID- 28746340
TI  - Effects of tanshinol on markers of bone turnover in ovariectomized rats and
      osteoblast cultures.
AB  - This study was aimed to explore the role of tanshinol in osteoblastic cells, and
      the role in vivo using an ovariectomized (OVX) rat model of osteoporosis. MC3T3
      E1 cells were pretreated with 0-400 MUg/mL tanshinol, and then cell viability,
      apoptosis, alkaline phosphatase (ALP) activity and the expressions of Collagen
      Type I Alpha 1 (Col1A1), Runt Related Transcription Factor 2 (Runx2) and
      osteocalcin (OCN) were respectively detected. Rats underwent OVX surgery was
      intervened with 5 mg/kg tanshinol or 25 MUg/kg beta-estradiol (E2) for 12 weeks.
      The triglycerides (TG), total cholesterol (TC), high and low density lipoprotein
      cholesterol (HDL-C and LDL-C), ALP, OCN and Tartrate-resistant acid phosphatase
      5b (TRACP-5b) contents were measured. Besides, the expressions of main factors in
      nuclear factor-kappa B (NF-kappaB) pathway were detected. The results showed that
      tanshinol significantly promoted MC3T3-E1 cells viability and ALP activity, while
      inhibited apoptosis (P < 0.05); Col1A1, Runx2 and OCN were all up-regulated by
      tanshinol (P < 0.05). In OVX rats, the contents of TG, TC, LDL-C, ALP, OCN and
      TRACP-5b were all increased (P < 0.05), while HDL-C was decreased (P < 0.05).
      Tanshinol significantly alleviated these aberrant regulations (P < 0.05).
      Inhibitory subunit of NF-kappaB (IkappaBalpha) and p65 were both remarkably
      phosphorylated by OVX, while this phosphorylation was partially neutralized by
      tanshinol (P < 0.05). In conclusion, we demonstrated that tanshinol exerted a
      bone-protective function by modulating the markers of bone turnover possibly via
      blocking NF-kappaB pathway. This study will provide new evidence that tanshinol
      is a potential therapeutic option for the relief of estrogen deficiency-induced
      osteoporosis.

PMID- 28746341
TI  - Association of prenatal exposure to benzodiazepines and child internalizing
      problems: A sibling-controlled cohort study.
AB  - BACKGROUND: During pregnancy, many women experience sleep problems and anxiety
      that require treatment. The long-term safety for the child of maternal
      benzodiazepine (BZD) and z-hypnotic use during pregnancy remains controversial.
      METHOD: We conducted a cohort and a sibling control study using data from the
      Norwegian Mother and Child Cohort Study. Data on use of BZD and z-hypnotics,
      internalizing and externalizing outcomes, and covariates were collected from
      mothers at gestational weeks 17 and 30 and when children were 0.5, 1.5, and 3
      years of age. The total sample consisted of 71,996 children (19,297 siblings) at
      1.5 years and 55,081 children (13,779 siblings) at 3 years. Short-term use was
      defined as use in one pregnancy period only. Long-term use was defined as use in
      two or more pregnancy periods. Linear full cohort random-effect and sibling
      matched fixed-effect regression models were used to compare internalizing and
      externalizing behavior in children prenatally exposed compared to those unexposed
      in the full cohort of pregnancies accounting for family clusters, as well as
      within sibling clusters comparing pregnancies with discordant exposures.
      Propensity score (PS) adjustment included variables on indication for use (sleep
      problems, symptoms of anxiety and depression) and other potential confounding
      factors. RESULTS: Long-term prenatal exposure to BZD or z-hypnotics was
      associated with increased internalizing behavior in crude cohort analyses and at
      age 1.5 years after PS adjustment in sibling-matched fixed-effect models [beta
      0.60, 95% confidence interval 0.17-0.95]. Analyses on specific drug groups showed
      that prenatal exposure to BZD-anxiolytics was associated with increased
      internalizing problems at both 1.5 years [beta 0.25, 0.01-0.49] and 3 years [beta
      0.26, 0.002-0.52] while exposure to z-hypnotics was not associated with any
      adverse outcomes after adjustment. CONCLUSION: The findings suggest a moderate
      association between BZD-anxiolytic exposure and child internalizing problems that
      is not likely due to stable familial confounding factors.

PMID- 28746342
TI  - The mechanism of monomer transfer between two structurally distinct PrP
      oligomers.
AB  - In mammals, Prion pathology refers to a class of infectious neuropathologies
      whose mechanism is based on the self-perpetuation of structural information
      stored in the pathological conformer. The characterisation of the PrP folding
      landscape has revealed the existence of a plethora of pathways conducing to the
      formation of structurally different assemblies with different biological
      properties. However, the biochemical interconnection between these diverse
      assemblies remains unclear. The PrP oligomerisation process leads to the
      formation of neurotoxic and soluble assemblies called O1 oligomers with a high
      size heterodispersity. By combining the measurements in time of size distribution
      and average size with kinetic models and data assimilation, we revealed the
      existence of at least two structurally distinct sets of assemblies, termed Oa and
      Ob, forming O1 assemblies. We propose a kinetic model representing the main
      processes in prion aggregation pathway: polymerisation, depolymerisation, and
      disintegration. The two groups interact by exchanging monomers through a
      disintegration process that increases the size of Oa. Our observations suggest
      that PrP oligomers constitute a highly dynamic population.

PMID- 28746343
TI  - An analysis of retrospective and repeat prospective reports of adverse childhood
      experiences from the South African Birth to Twenty Plus cohort.
AB  - Most studies rely on cross-sectional retrospective reports from adult samples to
      collect information about adverse childhood experiences (ACEs) to examine
      relationships with adult outcomes. The problems associated with these reports
      have long been debated, with only a few studies determining their reliability and
      validity and fewer still reaching consensus on the matter. This paper uses repeat
      prospective and retrospective reports of adverse childhood experiences from two
      respondent sources in the South African Birth to Twenty Plus (Bt20+) cohort to
      explore agreement and concordance in the prospective reporting of ACEs by
      caregivers and respective children as adolescents and then as young adults. The
      findings demonstrate little overall agreement between prospective and
      retrospective accounts of childhood experiences, with 80% of kappa values below
      the moderate agreement cutoff (k = .41). The highest levels of agreement were
      found between prospective and retrospective reporting on parental and household
      death (kappas ranging from .519 to .944). Comparisons between prospective
      caregiver reports and retrospective young adult reports yielded high concordance
      rates on sexual and physical abuse and exposure to intimate partner violence
      (91.0%, 87.7% and 80.2%, respectively). The prevalence of reported ACEs varied
      with the age of the respondent, with adolescents reporting much higher rates of
      exposure to violence, physical and sexual abuse than are reported retrospectively
      or by caregivers. This variation may partly reflect actual changes in
      circumstances with maturation, but may be influenced by developmental stage and
      issues of memory, cognition and emotional state more than has been considered in
      previous analyses. More research, across disciplines, is needed to understand
      these processes and their effect on recall. Long-term prospective studies are
      critical for this purpose. In conclusion, methodological research that uses a
      range of information sources to establish the reliability and validity of both
      retrospective and prospective reports - recognizing that the two approaches may
      fundamentally answer different questions - should be encouraged.

PMID- 28746344
TI  - Treatment initiation among persons diagnosed with drug resistant tuberculosis in
      Johannesburg, South Africa.
AB  - BACKGROUND: In South Africa, roughly half of the drug-resistant TB cases
      diagnosed are reported to have been started on treatment. We determined the
      proportion of persons diagnosed with rifampicin resistant (RR-) TB who initiated
      treatment in Johannesburg after the introduction of decentralized RR-TB care in
      2011. METHODS: We retrospectively matched adult patients diagnosed with
      laboratory-confirmed RR-TB in Johannesburg from 07/2011-06/2012 with records of
      patients initiating RR-TB treatment at one of the city's four public sector
      treatment sites (one centralized, three decentralized). Patients were followed
      from date of diagnosis until the earliest of RR-TB treatment initiation, death,
      or 6 months' follow-up. We report diagnostic methods and outcomes, proportions
      initiating treatment, and median time from diagnosis to treatment initiation.
      RESULTS: 594 patients were enrolled (median age 34 (IQR 29-42), 287 (48.3%)
      female). Diagnosis was by GenoType MTBDRplus (Hain-Life-Science) line probe assay
      (LPA) (281, 47.3%), Xpert MTB/RIF (Cepheid) (258, 43.4%), or phenotypic drug
      susceptibility testing (DST) (30, 5.1%) with 25 (4.2%) missing a diagnosis
      method. 320 patients (53.8%) had multi-drug resistant TB, 158 (26.6%) rifampicin
      resistant TB by Xpert MTB/RIF, 102 (17.2%) rifampicin mono-resistance, and 14
      (2.4%) extensively drug-resistant TB. 256/594 (43.0%) patients initiated
      treatment, representing 70.7% of those who were referred for treatment (362/594).
      338/594 patients (57.0%) did not initiate treatment, including 104 (17.5%) who
      died before treatment was started. The median time from sputum collection to
      treatment initiation was 33 days (IQR 12-52). CONCLUSION: Despite decentralized
      RR-TB treatment, fewer than half the patients diagnosed in Johannesburg initiated
      appropriate treatment. Offering treatment at decentralized sites alone is not
      sufficient; improvements in linking patients diagnosed with RR-TB to effective
      treatment is essential.

PMID- 28746345
TI  - Cisplatin resistance in non-small cell lung cancer cells is associated with an
      abrogation of cisplatin-induced G2/M cell cycle arrest.
AB  - The efficacy of cisplatin-based chemotherapy in cancer is limited by the
      occurrence of innate and acquired drug resistance. In order to better understand
      the mechanisms underlying acquired cisplatin resistance, we have compared the
      adenocarcinoma-derived non-small cell lung cancer (NSCLC) cell line A549 and its
      cisplatin-resistant sub-line A549rCDDP2000 with regard to cisplatin resistance
      mechanisms including cellular platinum accumulation, DNA-adduct formation, cell
      cycle alterations, apoptosis induction and activation of key players of DNA
      damage response. In A549rCDDP2000 cells, a cisplatin-induced G2/M cell cycle
      arrest was lacking and apoptosis was reduced compared to A549 cells, although
      equitoxic cisplatin concentrations resulted in comparable platinum-DNA adduct
      levels. These differences were accompanied by changes in the expression of
      proteins involved in DNA damage response. In A549 cells, cisplatin exposure led
      to a significantly higher expression of genes coding for proteins mediating G2/M
      arrest and apoptosis (mouse double minute 2 homolog (MDM2), xeroderma pigmentosum
      complementation group C (XPC), stress inducible protein (SIP) and p21) compared
      to resistant cells. This was underlined by significantly higher protein levels of
      phosphorylated Ataxia telangiectasia mutated (pAtm) and p53 in A549 cells
      compared to their respective untreated control. The results were compiled in a
      preliminary model of resistance-associated signaling alterations. In conclusion,
      these findings suggest that acquired resistance of NSCLC cells against cisplatin
      is the consequence of altered signaling leading to reduced G2/M cell cycle arrest
      and apoptosis.

PMID- 28746346
TI  - Drosophila increase exploration after visually detecting predators.
AB  - Novel stimuli elicit behaviors that are collectively known as specific
      exploration. These behaviors allow the animal to become more familiar with the
      novel objects within its environment. Specific exploration is frequently
      suppressed by defensive reactions to predator cues. Herein, we examine if this
      suppression occurs in Drosophila melanogaster by measuring the response of these
      flies to wild harvested predators. The flies used in our experiments have been
      cultured and had not lived under predator threat for multiple decades. In a
      circular arena with centrally-caged predators, wild type Drosophila actively
      avoided the pantropical jumping spider, Plexippus paykulli, and the Texas unicorn
      mantis, Phyllovates chlorophaena, indicating an innate defensive reaction to
      these predators. Interestingly, wild type Drosophila males also avoided a
      centrally-caged mock spider, and the avoidance of the mock spider became
      exaggerated when it was made to move within the cage. Visually impaired
      Drosophila failed to detect and avoid the Plexippus paykulli and the moving mock
      spider, while the broadly anosmic orco2 mutants were fully capable of detecting
      and avoiding Plexippus paykulli, indicating that these flies principally relied
      upon vison to perceive the predator stimuli. During early exploration of the
      arena, exploratory activity increased in the presence of Plexippus paykulli and
      the moving mock spider. The elevated activity induced by Plexippus paykulli
      disappeared after the fly had finished exploring, suggesting the flies were
      capable of habituating the predator cues. Taken together, these results indicate
      that despite being isolated from predators for decades Drosophila will visually
      detect these predators, retain innate defensive behaviors, respond by increasing
      exploratory activity in the arena rather than suppressing activity, and may
      habituate to normal predator cues.

PMID- 28746347
TI  - Is there a correlation between socioeconomic disparity and functional outcome
      after acute ischemic stroke?
AB  - BACKGROUND: To investigate the impact of low socioeconomic status (SES),
      indicated by low level of education, occupation and income, on 3 months
      functional outcome after ischemic stroke. METHODS: We analyzed data from the
      China National Stroke Registry (CNSR), a multicenter and prospective registry of
      consecutive patients with acute cerebrovascular events occurred between September
      2007 and August 2008. 11226 patients with ischemic stroke had SES and clinical
      characteristics data collected at baseline and mRS measured as indicator of
      functional outcome in 3 months follow up. Multinomial and ordinal logistic
      regression models were performed to examine associations between SES and the
      functional outcome. RESULTS: At 3 months after stroke, 5.3% of total patients had
      mRS scored at 5, 11.3% at score 4, 11.1% at score 3, 14.4% at score 2, 34.2% at
      score 1 and 23.7% at score 0. Compared to patients with educational level of >= 6
      years and non-manual laboring, those < 6 years and manual laboring tended to have
      higher mRS score (P<0.001). Multinomial adjusted odds ratios (ORs) of outcome in
      manual workers were significantly increased (ORs from1.38 to 1.87), but OR in
      patients with less income was not significant. There were similar patterns of
      association The impact may be stronger in patients aged <65 years (P = 0.003,
      P<0.001 respectively) and being male (P = 0.001, P<0.001 respectively).
      CONCLUSIONS: Our study provides evidence that people who are relatively more
      deprived in socioeconomic status suffer poorer outcome after ischemic stroke. The
      influence of low educational level and manual laboring can be more intensive than
      low income level on 3-month outcome. Health policy and service should target the
      deprived populations to reduce the public health burden in the society.

PMID- 28746348
TI  - Adolescent values for immunisation programs in Australia: A discrete choice
      experiment.
AB  - OBJECTIVES: The importance of adolescent engagement in health decisions and
      public health programs such as immunisation is becoming increasingly recognised.
      Understanding adolescent preferences and further identifying barriers and
      facilitators for immunisation acceptance is critical to the success of adolescent
      immunisation programs. This study applied a discrete choice experiment (DCE) to
      assess vaccination preferences in adolescents. METHODS: This study was conducted
      as a cross-sectional, national online survey in Australian adolescents. The DCE
      survey evaluated adolescent vaccination preferences. Six attributes were assessed
      including disease severity, target for protection, price, location of vaccination
      provision, potential side effects and vaccine delivery method. A mixed logit
      model was used to analyse DCE data. RESULTS: This survey was conducted between
      December 2014 and January 2015. Of 800 adolescents aged 15 to 19 years, stronger
      preferences were observed overall for: vaccination in the case of a life
      threatening illness (p<0.001), lower price vaccinations (p<0.001), mild but
      common side effects (p = 0.004), delivery via a skin patch (p<0.001) and being
      administered by a family practitioner (p<0.001). Participants suggested that they
      and their families would be willing to pay AU$394.28 (95%CI: AU$348.40 to
      AU$446.92) more for a vaccine targeting a life threatening illness than a mild
      moderate illness, AU$37.94 (95%CI: AU$19.22 to AU$57.39) more for being
      vaccinated at a family practitioner clinic than a council immunisation clinic,
      AU$23.01 (95%CI: AU$7.12 to AU$39.24) more for common but mild and resolving side
      effects compared to rare but serious side effects, and AU$51.80 (95%CI: AU$30.42
      to AU$73.70) more for delivery via a skin patch than injection. CONCLUSIONS:
      Consideration of adolescent preferences may result in improved acceptance of,
      engagement in and uptake of immunisation programs targeted for this age group.

PMID- 28746349
TI  - New insights on the regulation of the adenine nucleotide pool of erythrocytes in
      mouse models.
AB  - The observation that induced torpor in non-hibernating mammals could result from
      an increased AMP concentration in circulation led our investigation to reveal
      that the added AMP altered oxygen transport of erythrocytes. To further study the
      effect of AMP in regulation of erythrocyte function and systemic metabolism, we
      generated mouse models deficient in key erythrocyte enzymes in AMP metabolism. We
      have previously reported altered erythrocyte adenine nucleotide levels
      corresponding to altered oxygen saturation in mice deficient in both CD73 and
      AMPD3. Here we further investigate how these Ampd3-/-/Cd73-/- mice respond to the
      administered dose of AMP in comparison with the control models of single enzyme
      deficiency and wild type. We found that Ampd3-/-/Cd73-/- mice are more sensitive
      to AMP-induced hypometabolism than mice with a single enzyme deficiency, which
      are more sensitive than wild type. A dose-dependent rightward shift of
      erythrocyte p50 values in response to increasing amounts of extracellular AMP was
      observed. We provide further evidence for the direct uptake of AMP by
      erythrocytes that is insensitive to dipyridamole, a blocker for ENT1. The uptake
      of AMP by the erythrocytes remained linear at the highest concentration tested,
      10mM. We also observed competitive inhibition of AMP uptake by ATP and ADP but
      not by the other nucleotides and metabolites tested. Importantly, our studies
      suggest that AMP uptake is associated with an erythrocyte ATP release that is
      partially sensitive to inhibition by TRO19622 and Ca++ ion. Taken together, our
      study suggests a novel mechanism by which erythrocytes recycle and maintain their
      adenine nucleotide pool through AMP uptake and ATP release.

PMID- 28746350
TI  - Differential effects of N-linked glycosylation of Vstm5 at multiple sites on
      surface expression and filopodia formation.
AB  - V-set and transmembrane domain-containing protein 5 (Vstm5), a newly
      characterized small membrane glycoprotein, can induce membrane protrusions in
      various cells. Vstm5 can modulate both the position and complexity of central
      neurons by altering their membrane morphology and dynamics. In this study, we
      investigated the significance of glycosylation in the expression and function of
      Vstm5. Four N-linked glycosylation sites (Asn43, Asn87, Asn101, and Asn108) are
      predicted to be located in the extracellular N-terminus of mouse Vstm5. Although
      all four sites were glycosylated, their functional roles may not be identical. N
      glycosylation at multiple sites affects differentially the function of Vstm5.
      Glycosylation at individual sites not only played essential roles in surface
      expression of Vstm5 but also in the formation of neuronal dendritic filopodia.
      These results indicate that N-linked glycosylation at multiple sites plays
      important roles by differentially influencing the expression, targeting, and
      biological activity of Vstm5.

PMID- 28746351
TI  - Modelling saliency attention to predict eye direction by topological structure
      and earth mover's distance.
AB  - A saliency attention model for predicting eye direction is proposed in this
      paper. This work is inspired by the success of the topological structure and
      Earth Mover's Distance (EMD) approach. Firstly, we extract visual saliency
      features such as color contrast, intensity contrast, orientation, and texture.
      Then, we eliminate disconnected regions in the feature maps to keep topological
      structure. Secondly, we calculate center surround difference using across-scale
      EMD between different scales feature maps, rather than utilizing the Difference
      of Gaussian (DoG), which is used in many other saliency attention models.
      Thirdly, we across-scale fuse the feature maps in different scale and same
      feature. Lastly, we take advantage of competition function to calculate feature
      maps in same feature to form a saliency map, which is use to predict eye
      direction. Experimental results demonstrated the proposed model outperformed the
      state-of-the-art schemes in eye direction prediction community.

PMID- 28746352
TI  - Eyes versus hands: How perceived stimuli influence motor actions.
AB  - Many studies showed that biological (e.g., gaze-shifts or hand movements) and non
      biological stimuli (e.g., arrows or moving points) redirect attention. Biological
      stimuli seem to be more suitable than non-biological to perform this task.
      However, the question remains if biological stimuli do have different influences
      on redirecting attention and if this property is dependent on how we react to
      those stimuli. In two separate experiments, participants interact either with a
      biological or a non-biological stimulus (experiment 1), or with two biological
      stimuli (gaze-shifts, hand movements)(experiment 2) to which they responded with
      two different actions (saccade, button press), either in a congruent or
      incongruent manner. Results from experiment 1 suggest that interacting with the
      biological stimulus lead to faster responses, compared to the non-biological
      stimulus, independent of the response type. Results from experiment 2 show longer
      reaction times when the depicted stimulus was not matching the response type
      (e.g., reacting with hand movements to a moving object or gaze-shift) compared to
      a matching condition, while especially the gaze-following condition (reacting
      with a gaze shift to a perceived gaze shift) led to the fastest responses. These
      results suggest that redirecting attention is not only dependent on the perceived
      stimulus but also on the way how those stimuli are responded to.

PMID- 28746353
TI  - Delayed breastfeeding initiation and infant survival: A systematic review and
      meta-analysis.
AB  - OBJECTIVE: To assess the existing evidence regarding breastfeeding initiation
      time and infant morbidity and mortality. STUDY DESIGN: We conducted a systematic
      review and meta-analysis. We searched Pubmed, Embase, Web of Science, CINAHL,
      Popline, LILACS, AIM, and Index Medicus to identify existing evidence. We
      included observational studies and randomized control trials that examined the
      association between breastfeeding initiation time and mortality, morbidity, or
      nutrition outcomes from birth through 12 months of age in a population of infants
      who all initiated breastfeeding. Two reviewers independently extracted data from
      eligible studies using a standardized form. We pooled effect estimates using
      fixed-effects meta-analysis. RESULTS: We pooled five studies, including 136,047
      infants, which examined the association between very early breastfeeding
      initiation and neonatal mortality. Compared to infants who initiated
      breastfeeding <=1 hour after birth, infants who initiated breastfeeding 2-23
      hours after birth had a 33% greater risk of neonatal mortality (95% CI: 13-56%,
      I2 = 0%), and infants who initiated breastfeeding >=24 hours after birth had a
      2.19-fold greater risk of neonatal mortality (95% CI: 1.73-2.77, I2 = 33%). Among
      the subgroup of infants exclusively breastfed in the neonatal period, those who
      initiated breastfeeding >=24 hours after birth had an 85% greater risk of
      neonatal mortality compared to infants who initiated <24 hours after birth (95%
      CI: 29-167%, I2 = 33%). CONCLUSIONS: Policy frameworks and models to estimate
      newborn and infant survival, as well as health facility policies, should consider
      the potential independent effect of early breastfeeding initiation.

PMID- 28746354
TI  - Spatio-temporal epidemiology of Japanese encephalitis in Nepal, 2007-2015.
AB  - Japanese encephalitis (JE) is a major public health problem in Nepal. For the
      effective management and surveillance of JE, a clear understanding of its
      epidemiology is essential. Therefore, we conducted descriptive and spatial
      analyses to understand the spatio-temporal distribution of JE in human in Nepal.
      From 2007 to 2015, 1,823 JE cases were reported with a cumulative mean incidence
      of 0.735/100,000 population and a case fatality rate of 6.6%. The death rate in
      the up-to-24 years of age group was 74%. The JE cases were most commonly reported
      in the age group of 1-14 years. There is a strong seasonal pattern of JE
      occurrence in Nepal which peaked in August and declined by October each year,
      which corresponds to the monsoon season. The JE cases were reported in 63 of 75
      districts (84%), expanding in the mountain and hill regions. There was a strong
      clustering of JE incidence in the south-western and south-eastern Terai region,
      which is endemic for JE. Therefore, the JE surveillance system should be improved
      to better understand the drivers of disease expansion in Nepal for instituting a
      control program.

PMID- 28746355
TI  - Multi-AGV path planning with double-path constraints by using an improved genetic
      algorithm.
AB  - This paper investigates an improved genetic algorithm on multiple automated
      guided vehicle (multi-AGV) path planning. The innovations embody in two aspects.
      First, three-exchange crossover heuristic operators are used to produce more
      optimal offsprings for getting more information than with the traditional two
      exchange crossover heuristic operators in the improved genetic algorithm. Second,
      double-path constraints of both minimizing the total path distance of all AGVs
      and minimizing single path distances of each AGV are exerted, gaining the optimal
      shortest total path distance. The simulation results show that the total path
      distance of all AGVs and the longest single AGV path distance are shortened by
      using the improved genetic algorithm.

PMID- 28746356
TI  - Metabolomic profiling of CSF in multiple sclerosis and neuromyelitis optica
      spectrum disorder by nuclear magnetic resonance.
AB  - Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are
      inflammatory diseases of the central nervous system. Although several studies
      have characterized the metabolome in the cerebrospinal fluid (CSF) from MS and
      NMOSD patients, comparative analyses between them and between the relapse and the
      remission of each disease have not been performed. Both univariate and
      multivariate analyses were used to compare 1H-NMR spectra of CSF from MS, NMOSD,
      and healthy controls (HCs). The statistical analysis showed alterations of eight
      metabolites that were dependent on the disease. Levels of 2-hydroxybutyrate,
      acetone, formate, and pyroglutamate were higher and levels of acetate and glucose
      were lower in both MS and NMOSD. Citrate was lower in MS patients, whereas
      lactate was higher in only NMOSD specifically. The shared feature of metabolic
      changes between MS and NMOSD may be related to altered energy metabolism and
      fatty acid biosynthesis in the brain. Another analysis to characterize relapse
      and remission status showed that isoleucine and valine were down-regulated in MS
      relapse compared to MS remission. The other metabolites identified in the disease
      comparison showed the same alterations regardless of disease activity. These
      findings would be helpful in understanding the biological background of these
      diseases, and distinguishing between MS and NMOSD, as well as determining the
      disease activity.

PMID- 28746357
TI  - Microbubble-based enhancement of radiation effect: Role of cell membrane ceramide
      metabolism.
AB  - Ultrasound (US) stimulated microbubbles (MB) is a new treatment approach that
      sensitizes cancer cells to radiation (XRT). The molecular pathways in this
      response remain unelucidated, however, previous data has supported a role for
      cell membrane-metabolism related pathways including an up regulation of UDP
      glycosyltransferase 8 (UGT8), which catalyzes the transfer of galactose to
      ceramide, a lipid that is associated with the induction of apoptotic signalling.
      In this study, the role of UGT8 in responses of prostate tumours to ultrasound
      stimulated microbubble radiation enhancement therapy is investigated. Experiments
      were carried out with cells in vitro and tumours in vivo in which UGT8 levels had
      been up regulated or down regulated. Genetically modified PC3 cells were treated
      with XRT, US+MB, or a combination of XRT+US+MB. An increase in the
      immunolabelling of ceramide was observed in cells where UGT8 was down-regulated
      as opposed to cells where UGT8 was either not regulated or was up-regulated.
      Clonogenic assays have revealed a decreased level of cellular survival with the
      down-regulation of UGT8. Xenograft tumours generated from stably transfected PC3
      cells were also treated with US+MB, XRT or US+MB+XRT. Histology demonstrated more
      cellular damage in tumours with down-regulated UGT8 in comparison with control
      tumours. In contrast, tumours with up-regulated UGT8 had less damage than control
      tumours. Power Doppler imaging indicated a reduction in the vascular index with
      UGT8 down-regulation and photoacoustic imaging revealed a reduction in oxygen
      saturation. This was contrary to when UGT8 was up regulated. The down regulation
      of UGT8 led to the accumulation of ceramide resulting in more cell death
      signalling and therefore, a greater enhancement of radiation effect when vascular
      disruption takes place through the use of ultrasound-stimulated microbubbles.

PMID- 28746358
TI  - (I Can't Get No) Saturation: A simulation and guidelines for sample sizes in
      qualitative research.
AB  - I explore the sample size in qualitative research that is required to reach
      theoretical saturation. I conceptualize a population as consisting of sub
      populations that contain different types of information sources that hold a
      number of codes. Theoretical saturation is reached after all the codes in the
      population have been observed once in the sample. I delineate three different
      scenarios to sample information sources: "random chance," which is based on
      probability sampling, "minimal information," which yields at least one new code
      per sampling step, and "maximum information," which yields the largest number of
      new codes per sampling step. Next, I use simulations to assess the minimum sample
      size for each scenario for systematically varying hypothetical populations. I
      show that theoretical saturation is more dependent on the mean probability of
      observing codes than on the number of codes in a population. Moreover, the
      minimal and maximal information scenarios are significantly more efficient than
      random chance, but yield fewer repetitions per code to validate the findings. I
      formulate guidelines for purposive sampling and recommend that researchers follow
      a minimum information scenario.

PMID- 28746359
TI  - Receiver Operating Characteristic curve analysis determines association of
      individual potato foliage volatiles with onion thrips preference, cultivar and
      plant age.
AB  - Tomato spotted wilt virus (TSWV) causes sporadic but serious disease in
      Australian potato crops. TSWV is naturally spread to potato by thrips of which
      Thrips tabaci is the most important. Prior studies indicated possible non
      preference of potato cultivars to T. tabaci. Select potato cultivars were
      assessed for non-preference to T. tabaci in paired and group choice trials.
      Cultivars 'Bismark', 'Tasman' and 'King Edward' were less preferred than
      'Atlantic', 'Russet Burbank' and 'Shepody'. Green leaf volatiles were sampled
      using solid-phase microextraction from the headspace of potato cultivars of two
      ages that differed in T. tabaci preference. Analysis of headspace volatile data
      using Receiver Operating Characteristic curves identified individual volatiles
      associated with T. tabaci preference and non-preference, young and old plants and
      individual cultivars. These data could be used to inform breeding programs for
      selection of T. tabaci resistance to assist with TSWV management, and biological
      testing of novel thrips management compounds.

PMID- 28746360
TI  - Synergistic effects of cognitive impairment on physical disability in all-cause
      mortality among men aged 80 years and over: Results from longitudinal older
      veterans study.
AB  - OBJECTIVE: We evaluated effects of the interrelationship between physical
      disability and cognitive impairment on long-term mortality of men aged 80 years
      and older living in a retirement community in Taiwan. METHODS: This prospective
      cohort study enrolled older men aged 80 and older living in a Veterans Care Home.
      Those with confirmed diagnosis of dementia were excluded. All participants
      received comprehensive geriatric assessment, including sociodemographic data,
      Charlson's Comorbidity Index (CCI), geriatric syndromes, activities of daily
      living (ADL) using the Barthel index and cognitive function using the Mini-Mental
      State Examination (MMSE). Subjects were categorized into normal cognitive
      function, mild cognitive deterioration, and moderate-to-severe cognitive
      impairment and were further stratified by physical disability status. Kaplan
      Meier log-rank test was used for survival analysis. After adjusting for
      sociodemographic characteristics and geriatric syndromes, Cox proportional
      hazards model was constructed to examine associations between cognitive function,
      disability and increased mortality risk. RESULTS: Among 305 male subjects aged
      85.1 +/- 4.1 years, 89 subjects died during follow-up (mean follow-up: 1.87 +/-
      0.90 years). Kaplan-Meier unadjusted analysis showed reduced survival probability
      associated with moderate-to-severe cognitive status and physical disability.
      Mortality risk increased significantly only for physically disabled subjects with
      simultaneous mild cognitive deterioration (adjusted HR 1.951, 95% CI 1.036-3.673,
      p = 0.038) or moderate-to-severe cognitive impairment (aHR 2.722, 95% CI 1.430
      5.181, p = 0.002) after adjusting for age, BMI, education levels, smoking status,
      polypharmacy, visual and hearing impairment, urinary incontinence, fall history,
      depressive symptoms and CCI. Mortality risk was not increased among physically
      independent subjects with or without cognitive impairment, and physically
      disabled subjects with intact cognition. CONCLUSIONS: Physical disability is a
      major risk factor for all-cause mortality among men aged 80 years and older, and
      risk increased synergistically when cognitive impairment was present. Cognitive
      impairment alone without physical disability did not increase mortality risk in
      this population.

PMID- 28746361
TI  - Identification of transcriptional biomarkers by RNA-sequencing for improved
      detection of beta2-agonists abuse in goat skeletal muscle.
AB  - In this paper, high-throughput RNA-sequencing (RNA-seq) was used to search for
      transcriptional biomarkers for beta2-agonists. In combination with drug
      mechanisms, a smaller group of genes with higher detection accuracy was screened
      out. Unknown samples were first predicted by this group of genes, and liquid
      chromatograph tandem mass spectrometer (LC-MS/MS) was applied to positive samples
      to validate the biomarkers. The results of principal component analysis (PCA),
      hierarchical cluster analysis (HCA) and discriminant analysis (DA) indicated that
      the eight genes screened by high-throughput RNA-seq were able to distinguish
      samples in the experimental group and control group. Compared with the nine genes
      selected from an earlier literature, 17 genes including these nine genes were
      proven to have a more satisfactory effect, which validated the accuracy of gene
      selection by RNA-seq. Then, six key genes were selected from the 17 genes
      according to the variable importance in projection (VIP) value of greater than 1.
      The test results using the six genes and 17 genes were similar, revealing that
      the six genes were critical genes. By using the six genes, three positive samples
      possibly treated with drugs were screened out from 25 unknown samples through DA
      and partial least squares discriminant analysis (PLS-DA). Then, the three samples
      were verified by a standard method, and mapenterol was detected in a sample.
      Therefore, the six genes can be used as biomarkers to detect beta2-agonists.
      Compared with the previous study, accurate detection of beta2-agonists abuse
      using six key genes is an improvement method, which show great significance in
      the monitoring of beta2-agonists abuse in animal husbandry.

PMID- 28746362
TI  - Survival predictors associated with signet ring cell carcinoma of the esophagus
      (SRCCE): A population-based retrospective cohort study.
AB  - PURPOSE: Signet ring cell carcinoma of the esophagus (SRCCE) is an uncommon tumor
      associated with significant morbidity and mortality. There is still no consensus
      regarding cut-off values for tumor size, age and optimal treatment for SRCCE.
      Thus, we elucidated the current survival outcomes of patients with SRCCE and
      analyzed factors associated with prognosis. METHODS: A retrospective cohort study
      based on the SEER (The Surveillance, Epidemiology, and End Results) program
      database was conducted. We identified 537 patients (461 men and 76 women) newly
      diagnosed with SRCCE between January 2004 and December 2014. A multivariate Cox
      proportional hazards model was utilized to measure the mortality-associated risk
      factors in patients with SRCCE after adjusting for various variables. RESULTS:
      The 1-, 2- and 5-year disease-specific mortalities (DSM) were 51.6%, 67.6%, and
      78.4%, respectively, and the median survival time was 12.0 months. The factors
      correlated with mortality hazard were marital status (unmarried versus married,
      Hazard Ratio (HR) = 1.443), tumor size (>= 5 cm versus < 5 cm, HR = 1.444), tumor
      grade (high grade versus low grade, HR = 3.001), condition of primary tumor (T4
      versus T1, HR = 2.178), regional lymph node metastasis (N1 versus N0, HR =
      1.739), further metastasis (M1 versus M0, HR = 1.951) and chemotherapy (receiving
      chemotherapy versus no chemotherapy, HR = 0.464). CONCLUSIONS: The contemporary 5
      year DSM was 78.4%. Being unmarried, having a tumor size >= 5 cm, a high tumor
      grade, a score of T4 for tumor invasion of adjacent organs, a score of N1 for
      regional lymph node metastasis, a score of M1 for distant metastasis and no
      chemotherapy were independent predictors of high DSM.

PMID- 28746363
TI  - MAK33 antibody light chain amyloid fibrils are similar to oligomeric precursors.
AB  - Little structural information is available so far on amyloid fibrils consisting
      of immunoglobulin light chains. It is not understood which features of the
      primary sequence of the protein result in fibril formation. We report here MAS
      solid-state NMR studies to identify the structured core of kappa-type variable
      domain light chain fibrils. The core contains residues of the CDR2 and the beta
      strands D, E, F and G of the native immunoglobulin fold. The assigned core region
      of the fibril is distinct in comparison to the core identified in a previous
      solid-state NMR study on AL-09 by Piehl at. al, suggesting that VL fibrils can
      adopt different topologies. In addition, we investigated a soluble oligomeric
      intermediate state, previously termed the alternatively folded state (AFS), using
      NMR and FTIR spectroscopy. The NMR oligomer spectra display a high degree of
      similarity when compared to the fibril spectra, indicating a high structural
      similarity of the two aggregation states. Based on comparison to the native state
      NMR chemical shifts, we suggest that fibril formation via domain-swapping seems
      unlikely. Moreover, we used our results to test the quality of different amyloid
      prediction algorithms.

PMID- 28746364
TI  - Construction of a high-density genetic map for grape using specific length
      amplified fragment (SLAF) sequencing.
AB  - Genetic maps are important tools in plant genomics and breeding. We report a
      large-scale discovery of single nucleotide polymorphisms (SNPs) using the
      specific length amplified fragment sequencing (SLAF-seq) technique for the
      construction of high-density genetic maps for two elite wine grape cultivars,
      'Chardonnay' and 'Beibinghong', and their 130 F1 plants. A total of 372.53 M
      paired-end reads were obtained after preprocessing. The average sequencing depth
      was 33.81 for 'Chardonnay' (the female parent), 48.20 for 'Beibinghong' (the male
      parent), and 12.66 for the F1 offspring. We detected 202,349 high-quality SLAFs
      of which 144,972 were polymorphic; 10,042 SNPs were used to construct a genetic
      map that spanned 1,969.95 cM, with an average genetic distance of 0.23 cM between
      adjacent markers. This genetic map contains the largest molecular marker number
      of the grape maps so far reported. We thus demonstrate that SLAF-seq is a
      promising strategy for the construction of high-density genetic maps; the map
      that we report here is a good potential resource for QTL mapping of genes linked
      to major economic and agronomic traits, map-based cloning, and marker-assisted
      selection of grape.

PMID- 28746365
TI  - Cbp80 is needed for the expression of piRNA components and piRNAs.
AB  - Cap binding protein 80 (Cbp80) is the larger subunit of the nuclear cap-binding
      complex (nCBC), which is known to play important roles in nuclear mRNA
      processing, export, stability and quality control events. Reducing Cbp80 mRNA
      levels in the female germline revealed that Cbp80 is also involved in defending
      the germline against transposable elements. Combining such knockdown experiments
      with large scale sequencing of small RNAs further showed that Cbp80 is involved
      in the initial biogenesis of piRNAs as well as in the secondary biogenesis
      pathway, the ping-pong amplification cycle. We further found that Cbp80 knockdown
      not only led to the upregulation of transposons, but also to delocalization of
      Piwi, Aub and Ago3, key factors in the piRNA biosynthesis pathway. Furthermore,
      compared to controls, levels of Piwi and Aub were also reduced upon knock down of
      Cbp80. On the other hand, with the same treatment we could not detect significant
      changes in levels or subcellular distribution (nuage localization) of piRNA
      precursor transcripts. This shows that Cbp80 plays an important role in the
      production and localization of the protein components of the piRNA pathway and it
      seems to be less important for the production and export of the piRNA precursor
      transcripts.

PMID- 28746366
TI  - Synthesis, fungicidal evaluation and 3D-QSAR studies of novel 1,3,4-thiadiazole
      xylofuranose derivatives.
AB  - 1,3,4-Thiadiazole and sugar-derived molecules have proven to be promising
      agrochemicals with growth promoting, insecticidal and fungicidal activities. In
      the research field of agricultural fungicide, applying union of active group we
      synthesized a new set of 1,3,4-thiadiazole xylofuranose derivatives and all of
      the compounds were characterized by 1H NMR and HRMS. In precise toxicity
      measurement, some of compounds exhibited more potent fungicidal activities than
      the most widely used commercial fungicide Chlorothalonil, promoting further
      research and development. Based on our experimental data, 3D-QSAR (three
      dimensional quantitative structure-activity relationship) was established and
      investigated using comparative molecular field analysis (CoMFA) and comparative
      molecular similarity indices analysis (CoMSIA) techniques, helping to better
      understand the structural requirements of lead compounds with high fungicidal
      activity and environmental compatibility.

PMID- 28746367
TI  - High-resolution isotopic evidence of specialised cattle herding in the European
      Neolithic.
AB  - Reconstructing stock herding strategies and land use is key to comprehending past
      human social organization and economy. We present laser-ablation strontium and
      carbon isotope data from 25 cattle (Bos taurus) to reconstruct mobility and infer
      herding management at the Swiss lakeside settlement of Arbon Bleiche 3, occupied
      for only 15 years (3384-3370 BC). Our results reveal three distinct isotopic
      patterns that likely reflect different herding strategies: 1) localized cattle
      herding, 2) seasonal movement, and 3) herding away from the site year-round.
      Different strategies of herding are not uniformly represented in various areas of
      the settlement, which indicates specialist modes of cattle management. The
      pressure on local fodder capacities and the need for alternative herding regimes
      must have involved diverse access to grazing resources. Consequently, the
      increasing importance of cattle in the local landscape was likely to have
      contributed to the progress of socio-economic differentiation in early
      agricultural societies in Europe.

PMID- 28746368
TI  - The genome-wide identification and transcriptional levels of DNA
      methyltransferases and demethylases in globe artichoke.
AB  - Changes to the cytosine methylation status of DNA, driven by the activity of C5
      methyltransferases (C5-MTases) and demethylases, exert an important influence
      over development, transposon movement, gene expression and imprinting. Three
      groups of C5-MTase enzymes have been identified in plants, namely MET
      (methyltransferase 1), CMT (chromomethyltransferases) and DRM (domains rearranged
      methyltransferases). Here the repertoire of genes encoding C5-MTase and
      demethylase by the globe artichoke (Cynara cardunculus var. scolymus) is
      described, based on sequence homology, a phylogenetic analysis and a
      characterization of their functional domains. A total of ten genes encoding C5
      MTase (one MET, five CMTs and four DRMs) and five demethylases was identified. An
      analysis of their predicted product's protein structure suggested an extensive
      level of conservation has been retained by the C5-MTases. Transcriptional
      profiling based on quantitative real time PCR revealed a number of differences
      between the genes encoding maintenance and de novo methyltransferases, sometimes
      in a tissue- or development-dependent manner, which implied a degree of
      functional specialization.

PMID- 28746370
TI  - Neogene Proto-Caribbean porcupinefishes (Diodontidae).
AB  - Fossil Diodontidae in Tropical America consist mostly of isolated and fused beak
      like jawbones, and tooth plate batteries. These durophagous fishes are powerful
      shell-crushing predators on shallow water invertebrate faunas from Neogene
      tropical carbonate bottom, rocky reefs and surrounding flats. We use an
      ontogenetic series of high-resolution micro CT of fossil and extant species to
      recognize external and internal morphologic characters of jaws and tooth plate
      batteries. We compare similar sizes of jaws and/or tooth-plates from both extant
      and extinct species. Here, we describe three new fossil species including
      ?Chilomycterus exspectatus n. sp. and ?Chilomycterus tyleri n. sp. from the late
      Miocene Gatun Formation in Panama, and ?Diodon serratus n. sp. from the middle
      Miocene Socorro Formation in Venezuela. Fossil Diodontidae review included
      specimens from the Neogene Basins of the Proto-Caribbean (Brazil: Pirabas
      Formation; Colombia: Jimol Formation, Panama: Gatun and Tuira formations;
      Venezuela: Socorro and Cantaure formations). Diodon is present in both the
      Atlantic and Pacific oceans, whereas the distribution of Chilomycterus is highly
      asymmetrical with only one species in the Pacific. It seems that Diodon was as
      abundant in the Caribbean/Western Atlantic during the Miocene as it is there
      today. We analyze the paleogeographic distribution of the porcupinefishes group
      in Tropical America, after the complete exhumation of the Panamanian isthmus
      during the Pliocene.

PMID- 28746369
TI  - Single and combined effect of retinoic acid and rapamycin modulate the
      generation, activity and homing potential of induced human regulatory T cells.
AB  - Adoptive transfer of CD4+CD25+FOXP3+ regulatory T cells (Treg cells) has been
      successfully utilized to treat graft versus host disease and represents a
      promising strategy for the treatment of autoimmune diseases and transplant
      rejection. The aim of this study was to evaluate the effects of all-trans
      retinoic acid (atRA) and rapamycin (RAPA) on the number, phenotype, homing
      markers expression, DNA methylation, and function of induced human Treg cells in
      short-term cultures. Naive T cells were polyclonally stimulated and cultured for
      five days in the presence of different combinations of IL-2, TGF-beta1, atRA and
      RAPA. The resulting cells were characterized by the expression of FOXP3,
      activation, surface and homing markers. Methylation of the Conserved Non-coding
      Sequence 2 was also evaluated. Functional comparison of the different culture
      conditions was performed by suppression assays in vitro. Culturing naive human T
      cells with IL-2/TGFbeta1 resulted in the generation of 54.2% of Treg cells
      (CD4+CD25+FOXP3+) whereas the addition of 100 nM atRA increased the yield of Treg
      cells to 66% (p = 0.0088). The addition of RAPA did not increase the number of
      Treg cells in any of these settings. Treg cells generated in the presence of atRA
      had an increased expression of the beta7 integrin to nearly 100% of the generated
      Treg cells, while RAPA treated cells showed enhanced expression of CXCR4. The
      differential expression of homing molecules highlights the possibility of
      inducing Treg cells with differential organ-specific homing properties. Neither
      atRA nor RAPA had an effect on the highly methylated CNS2 sites, supporting
      reports that their contribution to the lineage stability of Treg cells is not
      mediated by methylation changes in this locus. Treg cells generated in the
      presence of RAPA show the most potent suppression effect on the proliferation of
      effector cells.

PMID- 28746371
TI  - Ionizing radiation response of primary normal human lens epithelial cells.
AB  - Whilst the cataractogenic potential of ionizing radiation has been known for over
      the past 120 years, little is known about radiation responses of lens cells. Our
      previous work was the first to evaluate the radiosensitivity of lens cells with
      the clonogenic assay, documenting that the survival of HLEC1 human lens
      epithelial cells is comparable to that of WI-38 human lung fibroblasts. Moreover,
      HLEC1 cells were found to contain subsets where irradiation stimulates
      proliferation or facilitates formation of abortive colonies with fewer cells than
      human fibroblasts. This study aims to gain insights into these mechanisms.
      Irradiation of HLEC1 cells with 10% survival dose caused a growth delay but did
      not reduce viability. HLEC1 cells at high cumulative population doubling level
      were more susceptible to radiogenic premature senescence than WI-38 cells.
      Concerning p53 binding protein 1 (53BP1) foci, HLEC1 cells harbored less
      spontaneous foci but more radiogenic foci than in WI-38 cells, and the focus
      number returned to spontaneous levels within 48 h postirradiation both in HLEC1
      and WI-38. The chemical inhibition of DNA repair kinases ataxia telangiectasia
      mutated, DNA-dependent protein kinase or both delayed and attenuated the
      appearance and disappearance of radiogenic 53BP1 foci, increased radiogenic
      premature senescence and enhanced clonogenic inactivation. The DNA microarray
      analysis suggested both radiogenic stimulation and inhibition of cell
      proliferation. Treatment with conditioned medium from irradiated cells did not
      change growth and the plating efficiency of nonirradiated cells. These results
      partially explain mechanisms of our previous observations, such that unrepaired
      or incompletely repaired DNA damage causes a growth delay in a subset of HLEC1
      cells without changing viability through induction of premature senescence,
      thereby leading to clonogenic inactivation, but that growth is stimulated in
      another subset via as yet unidentified mechanisms, warranting further studies.

PMID- 28746372
TI  - Multidrug-resistant gonorrhea: A research and development roadmap to discover new
      medicines.
AB  - Emilie Alirol and colleagues discuss the development of new treatments for
      gonorrhea.

PMID- 28746373
TI  - Zika virus preferentially replicates in the female reproductive tract after
      vaginal inoculation of rhesus macaques.
AB  - Zika virus (ZIKV) is a mosquito-transmitted virus that can cause severe defects
      in an infected fetus. ZIKV is also transmitted by sexual contact, although the
      relative importance of sexual transmission is unclear. To better understand the
      role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP) model
      of vaginal transmission was developed. ZIKV was readily transmitted to mature
      cycling female rhesus macaque (RM) by vaginal inoculation with 104-106 plaque
      forming units (PFU). However, there was variability in susceptibility between the
      individual RM with 1->8 vaginal inoculations required to establish infection.
      After treatment with Depoprovera, a widely used contraceptive progestin, two RM
      that initially resisted 8 vaginal ZIKV inoculations became infected after one
      ZIKV inoculation. Thus, Depoprovera seemed to enhance susceptibility to vaginal
      ZIKV transmission. Unexpectedly, the kinetics of virus replication and
      dissemination after intravaginal ZIKV inoculation were markedly different from RM
      infected with ZIKV by subcutaneous (SQ) virus inoculation. Several groups have
      reported that after SQ ZIKV inoculation vRNA is rapidly detected in blood plasma
      with vRNA less common in urine and saliva and only rarely detected in female
      reproductive tract (FRT) secretions. In contrast, in vaginally inoculated RM,
      plasma vRNA is delayed for several days and ZIKV replication in, and vRNA
      shedding from, the FRT was found in all 6 animals. Further, after intravaginal
      transmission ZIKV RNA shedding from FRT secretions was detected before or
      simultaneously with plasma vRNA, and persisted for at least as long. Thus, ZIKV
      replication in the FRT was independent of, and often preceded virus replication
      in the tissues contributing to plasma vRNA. These results support the conclusion
      that ZIKV preferentially replicates in the FRT after vaginal transmission, but
      not after SQ transmission, and raise the possibility that there is enhanced fetal
      infection and pathology after vaginal ZIKV transmission compared to a mosquito
      transmitted ZIKV.

PMID- 28746374
TI  - Spatial dynamics and control of a crop pathogen with mixed-mode transmission.
AB  - Trade or sharing that moves infectious planting material between farms can, for
      vertically-transmitted plant diseases, act as a significant force for dispersal
      of pathogens, particularly where the extent of material movement may be greater
      than that of infected vectors or inoculum. The network over which trade occurs
      will then effect dispersal, and is important to consider when attempting to
      control the disease. We consider the difference that planting material exchange
      can make to successful control of cassava brown streak disease, an important
      viral disease affecting one of Africa's staple crops. We use a mathematical model
      of smallholders' fields to determine the effect of informal trade on both the
      spread of the pathogen and its control using clean-seed systems, determining
      aspects that could limit the damage caused by the disease. In particular, we
      identify the potentially detrimental effects of markets, and the benefits of a
      community-based approach to disease control.

PMID- 28746375
TI  - Reduced dosage of the chromosome axis factor Red1 selectively disrupts the
      meiotic recombination checkpoint in Saccharomyces cerevisiae.
AB  - Meiotic chromosomes assemble characteristic "axial element" structures that are
      essential for fertility and provide the chromosomal context for meiotic
      recombination, synapsis and checkpoint signaling. Whether these meiotic processes
      are equally dependent on axial element integrity has remained unclear. Here, we
      investigated this question in S. cerevisiae using the putative condensin allele
      ycs4S. We show that the severe axial element assembly defects of this allele are
      explained by a linked mutation in the promoter of the major axial element gene
      RED1 that reduces Red1 protein levels to 20-25% of wild type. Intriguingly, the
      Red1 levels of ycs4S mutants support meiotic processes linked to axis integrity,
      including DNA double-strand break formation and deposition of the synapsis
      protein Zip1, at levels that permit 70% gamete survival. By contrast, the ability
      to elicit a meiotic checkpoint arrest is completely eliminated. This selective
      loss of checkpoint function is supported by a RED1 dosage series and is
      associated with the loss of most of the cytologically detectable Red1 from the
      axial element. Our results indicate separable roles for Red1 in building the
      structural axis of meiotic chromosomes and mounting a sustained recombination
      checkpoint response.

PMID- 28746376
TI  - Expressive intent, ambiguity, and aesthetic experiences of music and poetry.
AB  - A growing number of studies are investigating the way that aesthetic experiences
      are generated across different media. Empathy with a perceived human artist has
      been suggested as a common mechanism [1]. In this study, people heard 30 s
      excerpts of ambiguous music and poetry preceded by neutral, positively valenced,
      or negatively valenced information about the composer's or author's intent. The
      information influenced their perception of the excerpts-excerpts paired with
      positive intent information were perceived as happier and excerpts paired with
      negative intent information were perceived as sadder (although across intent
      conditions, musical excerpts were perceived as happier than poetry excerpts).
      Moreover, the information modulated the aesthetic experience of the excerpts in
      different ways for the different excerpt types: positive intent information
      increased enjoyment and the degree to which people found the musical excerpts to
      be moving, but negative intent information increased these qualities for poetry.
      Additionally, positive intent information was judged to better match musical
      excerpts and negative intent information to better match poetic excerpts. These
      results suggest that empathy with a perceived human artist is indeed an important
      shared factor across experiences of music and poetry, but that other mechanisms
      distinguish the generation of aesthetic appreciation between these two media.

PMID- 28746377
TI  - Evaluating the impact of a mandatory pre-abortion ultrasound viewing law: A mixed
      methods study.
AB  - BACKGROUND: Since mid-2013, Wisconsin abortion providers have been legally
      required to display and describe pre-abortion ultrasound images. We aimed to
      understand the impact of this law. METHODS: We used a mixed-methods study design
      at an abortion facility in Wisconsin. We abstracted data from medical charts one
      year before the law to one year after and used multivariable models,
      mediation/moderation analysis, and interrupted time series to assess the impact
      of the law, viewing, and decision certainty on likelihood of continuing the
      pregnancy. We conducted in-depth interviews with women in the post-law period
      about their ultrasound experience and analyzed them using elaborative and
      modified grounded theory. RESULTS: A total of 5342 charts were abstracted; 8.7%
      continued their pregnancies pre-law and 11.2% post-law (p = 0.002). A
      multivariable model confirmed the law was associated with higher odds of
      continuing pregnancy (aOR = 1.23, 95% CI: 1.01-1.50). Decision certainty (aOR =
      6.39, 95% CI: 4.72-8.64) and having to pay fully out of pocket (aOR = 4.98, 95%
      CI: 3.86-6.41) were most strongly associated with continuing pregnancy.
      Ultrasound viewing fully mediated the relationship between the law and continuing
      pregnancy. Interrupted time series analyses found no significant effect of the
      law but may have been underpowered to detect such a small effect. Nineteen of
      twenty-three women interviewed viewed their ultrasound image. Most reported no
      impact on their abortion decision; five reported a temporary emotional impact or
      increased certainty about choosing abortion. Two women reported that viewing
      helped them decide to continue the pregnancy; both also described preexisting
      decision uncertainty. CONCLUSIONS: This law caused an increase in viewing rates
      and a statistically significant but small increase in continuing pregnancy rates.
      However, the majority of women were certain of their abortion decision and the
      law did not change their decision. Other factors were more significant in women's
      decision-making, suggesting evaluations of restrictive laws should take account
      of the broader social environment.

PMID- 28746378
TI  - High-molecular weight adiponectin/HOMA-IR ratio as a biomarker of metabolic
      syndrome in urban multiethnic Brazilian subjects.
AB  - Metabolic syndrome (MetS) has an important epidemiological relevance due to its
      increasing prevalence and association with type 2 diabetes and cardiovascular
      disease. Insulin resistance is a core feature of the MetS. HOMA-IR is a robust
      clinical and epidemiological marker of MetS. Adiponectin is an adipokine with
      insulin-sensitizing and anti-inflammatory functions; its levels decrease as
      number of components of MetS increases. High-molecular weight adiponectin (HMWA)
      is the multimer responsible for the relationship of adiponectin with insulin
      sensitivity. HOMA-IR and HMWA are suitable candidates for MetS biomarkers. The
      ratio of adiponectin to HOMA-IR has been validated as a powerful index of MetS
      and considered a better marker of its presence, than either HOMA-IR or
      adiponectin alone, in selected homogeneous populations. We compared the strength
      of association between HMWA, HOMA-IR and HMWA/HOMA-IR ratio with MetS and its key
      components. Our data have shown that the median (25th, 75th percentile) of
      HMWA/HOMA-IR ratio was lower in subjects with MetS [0.51 (0.33, 1.31)] as
      compared to those without it [2.19 (1.13, 4.71)]. The correlation coefficient (r)
      was significantly higher for HMWA/HOMA-IR ratio as compared to HMWA for waist
      circumference (-0.65; -0.40, respectively); mean blood pressure (-0.27; -0.14,
      respectively); fasting glucose (-0.38; -0.19, respectively); HDL-cholesterol
      (0.44; 0.40, respectively); and triglycerides (-0.35; -0.18, respectively). In a
      multivariable logistic regression analysis, the HMWA/HOMA-IR ratio was a
      sensitive predictor for MetS, being the only marker that was significantly
      associated with each and all the individual components of the syndrome. These
      results expand on previous studies in that we used the active circulating form of
      adiponectin, i.e. HMWA, and represent a typical Brazilian cohort characterized by
      intense interethnic admixture. Thus, the HMWA/HOMA-IR ratio is a minimally
      invasive biomarker for MetS that could be clinically useful in prognosing patient
      outcome.

PMID- 28746379
TI  - Confirmation of independent introductions of an exotic plant pathogen of Cornus
      species, Discula destructiva, on the east and west coasts of North America.
AB  - Cornus florida (flowering dogwood) and C. nuttallii (Pacific dogwood) are North
      American native tree species that belong to the big-bracted group of dogwoods.
      Cornus species are highly valued for their ornamental characteristics, and have
      fruits that contain high fat content for animals. Also, they are an important
      understory tree in natural forests. Dogwood anthracnose, caused by Discula
      destructiva, was observed in the late 1970s on the east and west coasts of the
      United States and by 1991 had quickly spread throughout most of the native ranges
      of C. florida and C. nuttalli. We investigated the genetic diversity and
      population structure of 93 D. destructiva isolates using 47 microsatellite loci
      developed from the sequenced genome of the type strain of D. destructiva. Clone
      corrected data indicated low genetic diversity and the presence of four genetic
      clusters that corresponded to two major geographic areas, the eastern United
      States and the Pacific Northwest, and to the two collection time periods when the
      isolates were collected (pre- and post-1993). Linkage disequilibrium was present
      in five out of six subpopulations, suggesting that the fungus only reproduced
      asexually. Evidence of population bottlenecks was indicated across four
      identified genetic clusters, and was probably the result of the limited number of
      founding individuals on both coasts. These results support the hypothesis that D.
      destructiva is an exotic pathogen with independent introductions on the east and
      west coasts of North America. We also tested the cross-amplification of these
      microsatellite primers to other Discula species. Genomic DNA from 17 isolates of
      four other Discula species and two isolates of Juglanconis species (formerly
      Melanconis species) were amplified by 17 of 47 primer pairs. These primers may be
      useful for investigating the genetic diversity and population structure of these
      Discula species.

PMID- 28746380
TI  - Paleoproteomics of the Dental Pulp: The plague paradigm.
AB  - Chemical decomposition and fragmentation may limit the detection of ancient host
      and microbial DNA while some proteins can be detected for extended periods of
      time. We applied paleoproteomics on 300-year-old dental pulp specimens recovered
      from 16 individuals in two archeological funeral sites in France, comprising one
      documented plague site and one documented plague-negative site. The dental pulp
      paleoproteome of the 16 teeth comprised 439 peptides representative of 30
      proteins of human origin and 211 peptides representative of 27 proteins of non
      human origin. Human proteins consisted of conjunctive tissue and blood proteins
      including IgA immunoglobulins. Four peptides were indicative of three presumable
      Yersinia pestis proteins detected in 3/8 dental pulp specimens from the plague
      positive site but not in the eight dental pulp specimens collected in the plague
      negative site. Paleoproteomics applied to the dental pulp is a new and innovative
      approach to screen ancient individuals for the detection of blood-borne pathogens
      and host inflammatory response.

PMID- 28746381
TI  - Hedgehogs on the move: Testing the effects of land use change on home range size
      and movement patterns of free-ranging Ethiopian hedgehogs.
AB  - Degradation and alteration of natural environments because of agriculture and
      other land uses have major consequences on vertebrate populations, particularly
      on spatial organization and movement patterns. We used GPS tracking to study the
      effect of land use and sex on the home range size and movement of a typical model
      species, the Ethiopian hedgehogs. We used free-ranging hedgehogs from two areas
      with different land use practices: 24 from an area dominated by irrigated farms
      (12 ??, 12 ??) and 22 from a natural desert environment within a biosphere
      reserve (12 ??, 10 ??). Animals were significantly heavier in the resource-rich
      irrigated farms area (417.71 +/-12.77SE g) in comparison to the natural desert
      area (376.37+/-12.71SE g). Both habitat and sex significantly influenced the home
      range size of hedgehogs. Home ranges were larger in the reserve than in the farms
      area. Total home ranges averaged 103 ha (+/-17 SE) for males and 42 ha (+/-11SE)
      for females in the farms area, but were much larger in the reserve averaging 230
      ha (+/-33 SE) for males and 150 ha (+/-29 SE) for females. The home ranges of
      individuals of both sexes overlapped. Although females were heavier than males,
      body weight had no effect on home range size. The results suggest that resources
      provided in the farms (e.g. food, water, and shelters) influenced animal density
      and space use. Females aggregated around high-resource areas (either farms or
      rawdhats), whereas males roamed over greater distances, likely in search of
      mating opportunities to maximize reproductive success. Most individual home
      ranges overlapped with many other individuals of either sex, suggesting a non
      territorial, promiscuous mating. Patterns of space use and habitat utilization
      are key factors in shaping aspects of reproductive biology and mating system. To
      minimize the impacts of agriculture on local wildlife, we recommend that
      biodiversity-friendly agro-environmental schemes be introduced in the Middle East
      where the transformation from dry lands to 'islands of fertility' is often
      extreme.

PMID- 28746382
TI  - Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene.
AB  - BACKGROUND: Development of an effective non-viral vaccine against hepatitis C
      virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an
      attention and promising approach as a viable carrier for delivery of vaccine,
      gene, drug and other biomolecules in the body. AIM OF WORK: The present study
      aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2)
      gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine
      delivery system. METHODS AND RESULTS: Gel.NPs were synthesized and characterized
      (size: 150+/-2 nm and zeta potential +17.6 mv). NS2 gene was successfully cloned
      and expressed into E. coli M15 using pQE-30 vector. Antigenicity of the
      recombinant NS2 protein was confirmed by Western blotting to verify the
      efficiency of NS2 as a possible vaccine. Then NS2 gene was conjugated to gelatin
      nanoparticles and a successful conjugation was confirmed by labeling and imaging
      using Confocal Laser Scanning Microscope (CLSM). Interestingly, the
      transformation of the conjugated NS2/Gel.NPs complex into E. coli DH5-alpha was
      50% more efficient than transformation with the gene alone. In addition,
      conjugated NS2/Gel.NPs with ratio 1:100 (w/w) showed higher transformation
      efficiency into E. coli DH5-alpha than the other ratios (1:50 and 2:50).
      CONCLUSION: Gel.NPs effectively enhanced the gene delivery in bacterial cells
      without affecting the structure of NS2 gene and could be used as a safe, easy,
      rapid, cost-effective and non-viral vaccine delivery system for HCV.

PMID- 28746383
TI  - Validation of functional calibration and strap-down joint drift correction for
      computing 3D joint angles of knee, hip, and trunk in alpine skiing.
AB  - To obtain valid 3D joint angles with inertial sensors careful sensor-to-segment
      calibration (i.e. functional or anatomical calibration) is required and measured
      angular velocity at each sensor needs to be integrated to obtain segment and
      joint orientation (i.e. joint angles). Existing functional and anatomical
      calibration procedures were optimized for gait analysis and calibration movements
      were impractical to perform in outdoor settings. Thus, the aims of this study
      were 1) to propose and validate a set of calibration movements that were
      optimized for alpine skiing and could be performed outdoors and 2) to validate
      the 3D joint angles of the knee, hip, and trunk during alpine skiing. The
      proposed functional calibration movements consisted of squats, trunk rotations,
      hip ad/abductions, and upright standing. The joint drift correction previously
      proposed for alpine ski racing was improved by adding a second step to reduce
      separately azimuth drift. The system was validated indoors on a skiing carpet at
      the maximum belt speed of 21 km/h and for measurement durations of 120 seconds.
      Calibration repeatability was on average <2.7 degrees  (i.e. 3D joint angles
      changed on average <2.7 degrees  for two repeated sets of calibration movements)
      and all movements could be executed wearing ski-boots. Joint angle precision was
      <4.9 degrees  for all angles and accuracy ranged from -10.7 degrees  to 4.2
      degrees  where the presence of an athlete-specific bias was observed especially
      for the flexion angle. The improved joint drift correction reduced azimuth drift
      from over 25 degrees  to less than 5 degrees . In conclusion, the system was
      valid for measuring 3D joint angles during alpine skiing and could be used
      outdoors. Errors were similar to the values reported in other studies for gait.
      The system may be well suited for within-athlete analysis but care should be
      taken for between-athlete analysis because of a possible athlete-specific joint
      angle bias.

PMID- 28746384
TI  - Detection of brain-directed autoantibodies in the serum of non-small cell lung
      cancer patients.
AB  - Antibodies against brain proteins were identified in the plasma of cancer
      patients and are defined to cause paraneoplastic neurological syndromes. The
      profiles of brain-directed antibodies in non-small cell lung cancer (NSCLC) are
      largely unknown. Here, for the first time, we compared autoantibodies against
      brain proteins in NSCLC (n = 18) against those present in age-matched non-cancer
      control subjects (n = 18) with a similar life-style, habit, and medical history.
      Self-recognizing immunoglobulin (IgG) are primarily directed against cells in the
      cortex (P = 0.008), hippocampus (P = 0.003-0.05), and cerebellum (P = 0.02). More
      specifically, IgG targets were prominent in the pyramidal, Purkinje, and granule
      cell layers. Furthermore, autoimmune IgG signals were localized to neurons (81%),
      astrocytes (48%), and endothelial (29%) cells. While cancer sera yielded overall
      higher intensity signals, autoantigens of 100, 65, 45, 37, and 30 kDa molecular
      weights were the most represented. Additionally, a group of 100 kDa proteins seem
      more prevalent in female adenocarcinoma patients (4/5, 80%). In conclusion, our
      results revealed autoantigen specificity in NSCLC, which implicitly depends on
      patient's demographics and disease history. Patients at risk for lung cancer but
      with no active disease revealed that the immune profile in NSCLC is disease
      dependent.

PMID- 28746385
TI  - Quantification of carotid plaque lipid content with magnetic resonance T2 mapping
      in patients undergoing carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: Techniques to stratify subgroups of patients with
      asymptomatic carotid artery disease are urgently needed to guide decisions on
      optimal treatment. Reliance on estimates of % luminal stenosis has not been
      effective, perhaps because that approach entirely disregards potentially
      important information on the pathological process in the wall of the artery.
      METHODS: Since plaque lipid is a key determinant of plaque behaviour we used a
      newly validated, high-sensitivity T2-mapping MR technique for a systematic survey
      of the quantity and distribution of plaque lipid in patients undergoing
      endarterectomy. Lipid percentage was quantified in 50 carotid endarterectomy
      patients. Lipid distribution was tested, using two imaging indices (contribution
      of the largest lipid deposit towards total lipid (LLD %) and a newly-developed
      LAI 'lipid aggregation index'). RESULTS: The bifurcation contained maximal lipid
      volume. Lipid percentage was higher in symptomatic vs. asymptomatic patients with
      degree of stenosis (DS >= 50%) and in the total cohort (P = 0.013 and P = 0.005,
      respectively). Both LLD % and LAI was higher in symptomatic patients (P = 0.028
      and P = 0.018, respectively), suggesting that for a given plaque lipid volume,
      coalesced deposits were more likely to be associated with symptomatic events.
      There was no correlation between plaque volume or lipid content and degree of
      luminal stenosis measured on ultrasound duplex (r = -0.09, P = 0.53 and r = 
      0.05, P = 0.75), respectively. However, there was a strong correlation in lipid
      between left and right carotid arteries (r = 0.5, P <0.0001, respectively).
      CONCLUSIONS: Plaque lipid content and distribution is associated with symptomatic
      status of the carotid plaque. Importantly, plaque lipid content was not related
      to the degree of luminal stenosis assessed by ultrasound. Determination of plaque
      lipid content may prove useful for stratification of asymptomatic patients,
      including selection of optimal invasive treatments.

PMID- 28746386
TI  - TRACMIT: An effective pipeline for tracking and analyzing cells on micropatterns
      through mitosis.
AB  - The use of micropatterns has transformed investigations of dynamic biological
      processes by enabling the reproducible analysis of live cells using time-lapse
      fluorescence microscopy. With micropatterns, thousands of individual cells can be
      efficiently imaged in parallel, rendering the approach well suited for screening
      projects. Despite being powerful, such screens remain challenging in terms of
      data handling and analysis. Typically, only a fraction of micropatterns is
      occupied in a manner suitable to monitor a given phenotypic output. Moreover, the
      presence of dying or otherwise compromised cells complicates the analysis.
      Therefore, focusing strictly on relevant cells in such large time-lapse
      microscopy dataset poses interesting analysis challenges that are not readily met
      by existing software packages. This motivated us to develop an image analysis
      pipeline that handles all necessary image processing steps within one open-source
      platform to detect and analyze individual cells seeded on micropatterns through
      mitosis. We introduce a comprehensive image analysis pipeline running on Fiji
      termed TRACMIT (pipeline for TRACking and analyzing cells on micropatterns
      through MITosis). TRACMIT was developed to rapidly and accurately assess the
      orientation of the mitotic spindle during metaphase in time-lapse fluorescence
      microscopy of human cells expressing mCherry::histone 2B and plated on L-shaped
      micropatterns. This solution enables one to perform the entire analysis from the
      raw data, avoiding the need to save intermediate images, thereby decreasing data
      volume and thus reducing the data that needs to be processed. We first select
      micropatterns containing a single cell and then identify anaphase figures in the
      time-lapse recording. Next, TRACMIT tracks back in time until metaphase, when the
      angle of the mitotic spindle with respect to the micropattern is assessed. We
      designed the pipeline to allow for manual validation of selected cells with a
      simple user interface, and to enable analysis of cells plated on micropatterns of
      different shapes. For ease of use, the entire pipeline is provided as a series of
      Fiji/ImageJ macros, grouped into an ActionBar. In conclusion, the open source
      TRACMIT pipeline enables high-throughput analysis of single mitotic cells on
      micropatterns, thus accurately and efficiently allowing automatic determination
      of spindle positioning from time-lapse recordings.

PMID- 28746387
TI  - Psychometric properties of the Dresden Body Image Questionnaire: A multiple-group
      confirmatory factor analysis across sex and age in a Dutch non-clinical sample.
AB  - BACKGROUND: Body image has implications for psychosocial functioning and quality
      of life and its disturbance is reported in a broad range of psychiatric
      disorders. In view of the lack of instruments in Dutch measuring body image as a
      broad concept, we set out to make an instrument available that reflects the
      multidimensional character of this construct by including more dimensions than
      physical appearance. The Dresden Korperbildfragebogen (DBIQ, Dresden Body Image
      Questionnaire) particularly served this purpose. The DBIQ consists of 35 items
      and five subscales: body acceptance, sexual fulfillment, physical contact,
      vitality, and self-aggrandizement. The main objective of the present study was to
      evaluate the psychometric properties of the Dutch translation of the Dresden Body
      Image Questionnaire (DBIQ-NL) in a non-clinical sample. METHODS: The psychometric
      properties of the DBIQ-NL were examined in a non-clinical sample of 988
      respondents aged between 18 and 65. We investigated the subscales' internal
      consistency and test-retest reliability. In order to establish construct validity
      we evaluated the association with a related construct, body cathexis, and with
      indices of self-esteem and psychological wellbeing. The factor structure of the
      DBIQ-NL was examined via confirmatory factor analysis (CFA). The equivalence of
      the measurement model across sex and age was evaluated by multiplegroup
      confirmatory factor analyses. RESULTS: Confirmatory factor analyses showed a
      structure in accordance with the original scale, where model fit was improved
      significantly by moving one item to another subscale. Multiple group confirmatory
      factor analysis across sex and age demonstrated partial strong invariance.
      Internal consistency was good with little overlap between the subscales. Temporal
      reliability and construct validity were satisfactory. CONCLUSION: Results
      indicate that the DBIQ-NL is a reliable and valid instrument for non-clinical
      subjects. This provides a sound basis for further investigation of the DBIQ-NL in
      a clinical sample.

PMID- 28746388
TI  - The role of personality in health care use: Results of a population-based
      longitudinal study in Germany.
AB  - OBJECTIVE: To determine the role of personality in health care use
      longitudinally. METHODS: Data were derived from the German Socio-Economic Panel
      (GSOEP), a nationally representative, longitudinal cohort study of German
      households starting in 1984. Concentrating on the role of personality, we used
      data from the years 2005, 2009 and 2013. Personality was measured by using the
      GSOEP Big Five Inventory (BFI-S). Number of physician visits in the last 3 months
      and hospital stays in the last year were used as measures of health care use.
      RESULTS: Adjusting for predisposing factors, enabling resources, and need
      factors, fixed effects regressions revealed that physician visits increased with
      increasing neuroticism, whereas extraversion, openness to experience,
      agreeableness and conscientiousness did not affect physician visits in a
      significant way. The effect of self-rated health on physician visits was
      significantly moderated by neuroticism. Moreover, fixed effects regressions
      revealed that the probability of hospitalization in the past year increased with
      increasing extraversion, whereas the other personality factors did not affect
      this outcome measure significantly. CONCLUSION: Our findings suggest that changes
      in neuroticism are associated with changes in physician visits and that changes
      in extraversion are associated with the probability of hospitalization. Since
      recent studies have shown that treatments can modify personality traits,
      developing interventional strategies should take into account personality
      factors. For example, efforts to intervene in changing neuroticism might have
      beneficial effects for the healthcare system.

PMID- 28746389
TI  - A model for simulating the active dispersal of juvenile sea turtles with a case
      study on western Pacific leatherback turtles.
AB  - Oceanic currents are known to broadly shape the dispersal of juvenile sea turtles
      during their pelagic stage. Accordingly, simple passive drift models are widely
      used to investigate the distribution at sea of various juvenile sea turtle
      populations. However, evidence is growing that juveniles do not drift purely
      passively but also display some swimming activity likely directed towards
      favorable habitats. We therefore present here a novel Sea Turtle Active Movement
      Model (STAMM) in which juvenile sea turtles actively disperse under the combined
      effects of oceanic currents and habitat-driven movements. This model applies to
      all sea turtle species but is calibrated here for leatherback turtles
      (Dermochelys coriacea). It is first tested in a simulation of the active
      dispersal of juveniles originating from Jamursba-Medi, a main nesting beach of
      the western Pacific leatherback population. Dispersal into the North Pacific
      Ocean is specifically investigated. Simulation results demonstrate that, while
      oceanic currents broadly shape the dispersal area, modeled habitat-driven
      movements strongly structure the spatial and temporal distribution of juveniles
      within this area. In particular, these movements lead juveniles to gather in the
      North Pacific Transition Zone (NPTZ) and to undertake seasonal north-south
      migrations. More surprisingly, juveniles in the NPTZ are simulated to swim mostly
      towards west which considerably slows down their progression towards the American
      west coast. This increases their residence time, and hence the risk of
      interactions with fisheries, in the central and eastern part of the North Pacific
      basin. Simulated habitat-driven movements also strongly reduce the risk of cold
      induced mortality. This risk appears to be larger among the juveniles that
      rapidly circulate into the Kuroshio than among those that first drift into the
      North Equatorial Counter Current (NECC). This mechanism might induce marked
      interannual variability in juvenile survival as the strength and position of the
      NECC are directly linked to El Nino activity.

PMID- 28746390
TI  - Homogenized modeling methodology for 18650 lithium-ion battery module under large
      deformation.
AB  - Effective lithium-ion battery module modeling has become a bottleneck for full
      size electric vehicle crash safety numerical simulation. Modeling every single
      cell in detail would be costly. However, computational accuracy could be lost if
      the module is modeled by using a simple bulk material or rigid body. To solve
      this critical engineering problem, a general method to establish a computational
      homogenized model for the cylindrical battery module is proposed. A single
      battery cell model is developed and validated through radial compression and
      bending experiments. To analyze the homogenized mechanical properties of the
      module, a representative unit cell (RUC) is extracted with the periodic boundary
      condition applied on it. An elastic-plastic constitutive model is established to
      describe the computational homogenized model for the module. Two typical packing
      modes, i.e., cubic dense packing and hexagonal packing for the homogenized
      equivalent battery module (EBM) model, are targeted for validation compression
      tests, as well as the models with detailed single cell description. Further, the
      homogenized EBM model is confirmed to agree reasonably well with the detailed
      battery module (DBM) model for different packing modes with a length scale of up
      to 15 * 15 cells and 12% deformation where the short circuit takes place. The
      suggested homogenized model for battery module makes way for battery module and
      pack safety evaluation for full-size electric vehicle crashworthiness analysis.

PMID- 28746391
TI  - Correction: Acute and Chronic Sustained Hypoxia Do Not Substantially Regulate
      Amyloid-beta Peptide Generation In Vivo.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0170345.].

PMID- 28746392
TI  - Design, characterization and experimental validation of a compact, flexible
      pulsed power architecture for ex vivo platelet activation.
AB  - Electric pulses can induce various changes in cell dynamics and properties
      depending upon pulse parameters; however, pulsed power generators for in vitro
      and ex vivo applications may have little to no flexibility in changing the pulse
      duration, rise- and fall-times, or pulse shape. We outline a compact pulsed power
      architecture that operates from hundreds of nanoseconds (with the potential for
      modification to tens of nanoseconds) to tens of microseconds by modifying a Marx
      topology via controlling switch sequences and voltages into each capacitor stage.
      We demonstrate that this device can deliver pulses to both low conductivity
      buffers, like standard pulsed power supplies used for electroporation, and higher
      conductivity solutions, such as blood and platelet rich plasma. We further test
      the effectiveness of this pulse generator for biomedical applications by
      successfully activating platelets ex vivo with 400 ns and 600 ns electric pulses.
      This novel bioelectrics platform may provide researchers with unprecedented
      flexibility to explore a wide range of pulse parameters that may induce phenomena
      ranging from intracellular to plasma membrane manipulation.

PMID- 28746393
TI  - Dynamic hyper-editing underlies temperature adaptation in Drosophila.
AB  - In Drosophila, A-to-I editing is prevalent in the brain, and mutations in the
      editing enzyme ADAR correlate with specific behavioral defects. Here we
      demonstrate a role for ADAR in behavioral temperature adaptation in Drosophila.
      Although there is a higher level of editing at lower temperatures, at 29 degrees
      C more sites are edited. These sites are less evolutionarily conserved, more
      disperse, less likely to be involved in secondary structures, and more likely to
      be located in exons. Interestingly, hypomorph mutants for ADAR display a weaker
      transcriptional response to temperature changes than wild-type flies and a highly
      abnormal behavioral response upon temperature increase. In sum, our data shows
      that ADAR is essential for proper temperature adaptation, a key behavior trait
      that is essential for survival of flies in the wild. Moreover, our results
      suggest a more general role of ADAR in regulating RNA secondary structures in
      vivo.

PMID- 28746394
TI  - Effects of oxidative and thermal stresses on stress granule formation in human
      induced pluripotent stem cells.
AB  - Stress Granules (SGs) are dynamic ribonucleoprotein aggregates, which have been
      observed in cells subjected to environmental stresses, such as oxidative stress
      and heat shock (HS). Although pluripotent stem cells (PSCs) are highly sensitive
      to oxidative stress, the role of SGs in regulating PSC self-renewal and
      differentiation has not been fully elucidated. Here we found that sodium arsenite
      (SA) and HS, but not hydrogen peroxide (H2O2), induce SG formation in human
      induced (hi) PSCs. Particularly, we found that these granules contain the well
      known SG proteins (G3BP, TIAR, eIF4E, eIF4A, eIF3B, eIF4G, and PABP), were found
      in juxtaposition to processing bodies (PBs), and were disassembled after the
      removal of the stress. Moreover, we showed that SA and HS, but not H2O2, promote
      eIF2alpha phosphorylation in hiPSCs forming SGs. Analysis of pluripotent protein
      expression showed that HS significantly reduced all tested markers (OCT4, SOX2,
      NANOG, KLF4, L1TD1, and LIN28A), while SA selectively reduced the expression
      levels of NANOG and L1TD1. Finally, in addition to LIN28A and L1TD1, we
      identified DPPA5 (pluripotent protein marker) as a novel component of SGs.
      Collectively, these results provide new insights into the molecular cues of
      hiPSCs responses to environmental insults.

PMID- 28746395
TI  - The disease burden of human cystic echinococcosis based on HDRs from 2001 to 2014
      in Italy.
AB  - BACKGROUND: Cystic echinococcosis (CE) is an important neglected zoonotic
      parasitic infection belonging to the subgroup of seven Neglected Zoonotic Disease
      (NZDs) included in the World Health Organization's official list of 18 Neglected
      Tropical Diseases (NTDs). CE causes serious global human health concerns and
      leads to significant economic losses arising from the costs of medical treatment,
      morbidity, life impairments and fatality rates in human cases. Moreover, CE is
      endemic in several Italian Regions. The aim of this study is to perform a
      detailed analysis of the economic burden of hospitalization and treatment costs
      and to estimate the Disability Adjusted Life Years (DALYs) of CE in Italy.
      METHODS AND FINDINGS: In the period from 2001 to 2014, the direct costs of 21,050
      Hospital Discharge Records (HDRs) belonging to 12,619 patients with at least one
      CE-related diagnosis codes were analyzed in order to quantify the economic burden
      of CE. CE cases average per annum are 901 (min-max = 480-1,583). Direct costs
      include expenses for hospitalizations, medical and surgical treatment incurred by
      public and private hospitals and were computed on an individual basis according
      to Italian Health Ministry legislation. Moreover, we estimated the DALYs for each
      patient. The Italian financial burden of CE is around ? 53 million; the national
      average economic burden per annum is around ? 4 million; the DALYs of the
      population from 2001 to 2014 are 223.35 annually and 5.26 DALYs per 105
      inhabitants. CONCLUSION: In Italy, human CE is responsible for significant
      economic losses in the public health sector. In humans, costs associated with CE
      have been shown to have a great impact on affected individuals, their families
      and the community as a whole. This study could be used as a tool to prioritize
      and make decisions with regard to a surveillance system for this largely
      preventable yet neglected disease. It demonstrates the need of implementing a CE
      control program aimed at preventing the considerable economic and social losses
      it causes in high incidence areas.

PMID- 28746396
TI  - Recovery of metallo-tolerant and antibiotic resistant psychrophilic bacteria from
      Siachen glacier, Pakistan.
AB  - Cultureable bacterial diversity of previously unexplored Siachen glacier,
      Pakistan, was studied. Out of 50 isolates 33 (66%) were Gram negative and 17
      (34%) Gram positive. About half of the isolates were pigment producers and were
      able to grow at 4-37 degrees C. 16S rRNA gene sequences revealed Gram negative
      bacteria dominated by Proteobacteria (especially gamma-proteobacteria and beta
      proteobacteria) and Flavobacteria. The genus Pseudomonas (51.51%, 17) was
      dominant among gamma- proteobacteria. beta-proteobacteria constituted 4 (12.12%)
      Alcaligenes and 4 (12.12%) Janthinobacterium strains. Among Gram positive
      bacteria, phylum Actinobacteria, Rhodococcus (23.52%, 4) and Arthrobacter
      (23.52%, 4) were the dominating genra. Other bacteria belonged to Phylum
      Firmicutes with representative genus Carnobacterium (11.76%, 2) and 4 isolates
      represented 4 genera Bacillus, Lysinibacillus, Staphylococcus and Planomicrobium.
      Most of the Gram negative bacteria were moderate halophiles, while most of the
      Gram positives were extreme halophiles and were able to grow up to 6.12 M of
      NaCl. More than 2/3 of the isolates showed antimicrobial activity against
      multidrug resistant S. aureus, E. coli, Klebsiella pneumonia, Enterococcus
      faecium, Candida albicans, Aspergillus flavus and Aspergillus fumigatus and ATCC
      strains. Gram positive bacteria (94.11%) were more resistant to heavy metals as
      compared to Gram negative (78.79%) and showed maximum tolerance against iron and
      least tolerance against mercury.

PMID- 28746397
TI  - Biocide-mediated corrosion of coiled tubing.
AB  - Coiled tubing corrosion was investigated for 16 field water samples (S5 to S20)
      from a Canadian shale gas field. Weight loss corrosion rates of carbon steel
      beads incubated with these field water samples averaged 0.2 mm/yr, but injection
      water sample S19 had 1.25+/-0.07 mm/yr. S19 had a most probable number of zero
      acid-producing bacteria and incubation of S19 with carbon steel beads or coupons
      did not lead to big changes in microbial community composition. In contrast other
      field water samples had most probable numbers of APB of 102/mL to 107/mL and
      incubation of these field water samples with carbon steel beads or coupons often
      gave large changes in microbial community composition. HPLC analysis indicated
      that all field water samples had elevated concentrations of bromide (average 1.6
      mM), which may be derived from bronopol, which was used as a biocide. S19 had the
      highest bromide concentration (4.2 mM) and was the only water sample with a high
      concentration of active bronopol (13.8 mM, 2760 ppm). Corrosion rates increased
      linearly with bronopol concentration, as determined by weight loss of carbon
      steel beads, for experiments with S19, with filtered S19 and with bronopol
      dissolved in defined medium. This indicated that the high corrosion rate found
      for S19 was due to its high bronopol concentration. The corrosion rate of coiled
      tubing coupons also increased linearly with bronopol concentration as determined
      by electrochemical methods. Profilometry measurements also showed formation of
      multiple pits on the surface of coiled tubing coupon with an average pit depth of
      60 MUm after 1 week of incubation with 1 mM bronopol. At the recommended dosage
      of 100 ppm the corrosiveness of bronopol towards carbon steel beads was modest
      (0.011 mm/yr). Higher concentrations, resulting if biocide is added repeatedly as
      commonly done in shale gas operations, are more corrosive and should be avoided.
      Overdosing may be avoided by assaying the presence of residual biocide by HPLC,
      rather than by assaying the presence of residual surviving bacteria.

PMID- 28746398
TI  - Tomosyn associates with secretory vesicles in neurons through its N- and C
      terminal domains.
AB  - The secretory pathway in neurons requires efficient targeting of cargos and
      regulatory proteins to their release sites. Tomosyn contributes to synapse
      function by regulating synaptic vesicle (SV) and dense-core vesicle (DCV)
      secretion. While there is large support for the presynaptic accumulation of
      tomosyn in fixed preparations, alternative subcellular locations have been
      suggested. Here we studied the dynamic distribution of tomosyn-1 (Stxbp5) and
      tomosyn-2 (Stxbp5l) in mouse hippocampal neurons and observed a mixed diffuse and
      punctate localization pattern of both isoforms. Tomosyn-1 accumulations were
      present in axons and dendrites. As expected, tomosyn-1 was expressed in about 75%
      of the presynaptic terminals. Interestingly, also bidirectional moving tomosyn-1
      and -2 puncta were observed. Despite the lack of a membrane anchor these puncta
      co-migrated with synapsin and neuropeptide Y, markers for respectively SVs and
      DCVs. Genetic blockade of two known tomosyn interactions with synaptotagmin-1 and
      its cognate SNAREs did not abolish its vesicular co-migration, suggesting an
      interplay of protein interactions mediated by the WD40 and SNARE domains. We
      hypothesize that the vesicle-binding properties of tomosyns may control the
      delivery, pan-synaptic sharing and secretion of neuronal signaling molecules,
      exceeding its canonical role at the plasma membrane.

PMID- 28746399
TI  - Coordination of matrix attachment and ATP-dependent chromatin remodeling regulate
      auxin biosynthesis and Arabidopsis hypocotyl elongation.
AB  - Hypocotyl elongation is extensively controlled by hormone signaling networks. In
      particular, auxin metabolism and signaling play key roles in light-dependent
      hypocotyl growth. The nuclear matrix facilitates organization of DNA within the
      nucleus, and dynamic interactions between nuclear matrix and DNA are related to
      gene regulation. Conserved scaffold/matrix attachment regions (S/MARs) are
      anchored to the nuclear matrix by the AT-HOOK MOTIF CONTAINING NUCLEAR LOCALIZED
      (AHL) proteins in Arabidopsis. Here, we found that ESCAROLA (ESC)/AHL27 and
      SUPPRESSOR OF PHYTOCHROME B-4 #3 (SOB3)/AHL29 redundantly regulate auxin
      biosynthesis in the control of hypocotyl elongation. The light-inducible AHL
      proteins bind directly to an S/MAR region of the YUCCA 9 (YUC9) promoter and
      suppress its expression to inhibit hypocotyl growth in light-grown seedlings. In
      addition, they recruit the SWI2/SNF2-RELATED 1 (SWR1) complex and promote
      exchange of H2A with the histone variant H2A.Z at the YUC9 locus to further
      elaborately control auxin biosynthesis. Consistent with these results, the long
      hypocotyl phenotypes of light-grown genetic mutants of the AHLs and H2A.Z
      exchanging components were suppressed by potent chemical inhibitors of auxin
      transport and YUC enzymes. These results suggest that the coordination of matrix
      attachment and chromatin modification underlies auxin biosynthesis in light
      dependent hypocotyl growth.

PMID- 28746400
TI  - Associations between health culture, health behaviors, and health-related
      outcomes: A cross-sectional study.
AB  - BACKGROUND: To examine the associations between demographic characteristics,
      health behaviors, workplace health culture, and health-related outcomes in
      Chinese workplaces. METHODS: A total of 1508 employees from 10 administrative
      offices and 6 enterprises were recruited for a cross-sectional survey. Self
      administered questionnaires mainly addressed demographic characteristics, health
      behaviors, workplace health culture, and health-related outcomes including self
      rated health, mental health, and happiness. RESULTS: The proportion of
      participants who reported good health-related outcomes was significantly higher
      in those working in administrative offices than those working in enterprises. The
      result of the potential factors related to self-rated health (SRH), mental
      health, and happiness by logistic regression analyses showed that age and income
      were associated with SRH; type of workplace, age, smoking, and health culture at
      the workplace level were associated with mental health; and beneficial health
      effects of direct leadership was positively associated with happiness. Moreover,
      there were some similar results among 3 multivariate regression models. Firstly,
      good SRH (Odds Ratio (OR) = 1.744), mental health (OR = 1.891), and happiness (OR
      = 1.736) were more common among highly physically active participants compared
      with those physical inactive. Furthermore, passive smoking was negatively
      correlated with SRH (OR = 0.686), mental health (OR = 0.678), and happiness (OR =
      0.616), while health culture at the individual level was positively correlated
      with SRH (OR = 1.478), mental health (OR = 1.654), and happiness (OR = 2.916).
      CONCLUSIONS: The present study indicated that workplace health culture, health
      behaviors, and demographic characteristics were associated with health-related
      outcomes. Furthermore, individual health culture, physical activity, and passive
      smoking might play a critical role in workplace health promotion.

PMID- 28746401
TI  - Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with
      monoclonal antibodies.
AB  - This study describes the identification of one linear B-cell epitope on TMUV NS1
      protein with monoclonal antibody (mAb) 3G2 by indirect enzyme-linked
      immunosorbent assay (ELISA). In this study, NS1 protein was expressed in
      prokaryotic expression system and purified. One mAb against NS1 protein was
      generated from Balb/c mice immunized with recombinant protein NS1. A set of 35
      partially-overlapping polypeptides covering the entire NS1 protein was expressed
      with PGEX-6P-1 vector and screened with mAb 3G2. One polypeptide against the mAb
      was acquired and identified by indirect ELISA and western-blot. To map the
      epitope accurately, one or two amino acid residues were removed from the carboxy
      and amino terminal of polypeptide sequentially. A series of truncated
      oligopeptides were expressed and purified. The minimal determinant of the linear
      B cell epitope was recognized and identified with mAb 3G2. The accurate linear B
      cell epitope was 269DEKEIV274 located in NS1 protein. Furthermore, sequence
      alignment showed that the epitope was highly conserved and specific among TMUV
      strains and other flavivirus respectively. The linear B-cell epitope of TMUV NS1
      protein could benefit the development of new vaccines and diagnostic assays.

PMID- 28746402
TI  - Effects of Zn, macronutrients, and their interactions through foliar applications
      on winter wheat grain nutritional quality.
AB  - Although application of Zn combined with macronutrients (K, P, and N) can be used
      to fortify wheat grain with Zn, little is known about their interactions when
      foliar application is employed or the influences of common soil fertility
      management practices (e.g. N and straw management) on their efficiency.
      Therefore, the effects of foliar-applied Zn and N, P, or K on grain nutritional
      quality (especially Zn) were investigated in wheat grown under different soil N
      rates at two sites with (Sanyuan) or without (Yangling) employing straw return. A
      4-year-long field experiment was also conducted to evaluate the environmental
      stability of the foliar formulations. Across 6 site-years, foliar Zn application
      alone or combined with N, P, or K fertilizers resulted in 95.7%, 101%, 67.9% and
      121% increases in grain Zn concentration, respectively. In terms of increasing
      grain Zn concentration, foliar-applied Zn positively interacted with N (at
      Sanyuan) and K (at Yangling), but negatively interacted with P at any condition
      tested, suggesting depressive effects of foliarly-applied P on physiological
      availability of Zn. Although these interaction effects were the major factor that
      governing the efficiency of foliar-applied Zn combined with N, P, or K on grain
      Zn concentration, the magnitude of the increase/decrease in grain Zn (-3.96~5.71
      mg kg-1) due to these interactions was much less than the average increases
      following Zn+K (31.3), Zn+P (18.7), and Zn+N (26.5 mg kg-1) treatments relative
      to that observed in foliar Zn-only treatment. The combined foliar application of
      Zn with N, P, or K did not cause any adverse impact on grain yield and other
      nutritional quality and in some cases slightly increased grain yield and
      macronutrient concentrations. Grain phytic acid:Zn molar ratios were respectively
      52.0%, 53.1%, 43.4% and 63.5% lower in the foliar Zn, Zn+N, Zn+P and Zn+K
      treatments than in the control treatment. These effects were consistent over four
      years and across three soil N rates. Overall, combined foliar application of Zn
      with N, P, or K can successfully fortify wheat grain with Zn (above 40 mg kg-1),
      and including Zn in foliar N or K application are preferred for practically
      increasing dietary Zn intake.

PMID- 28746403
TI  - Change in children's school behavior after mass administration of praziquantel
      for Schistosoma mansoni infection in endemic areas of western Kenya: A pilot
      study using the Behavioral Assessment System for Children (BASC-2).
AB  - BACKGROUND: Schistosomiasis is a parasite-related chronic inflammatory condition
      that can cause anemia, decreased growth, liver abnormalities, and deficits in
      cognitive functioning among children. METHODOLOGY/PRINCIPAL FINDINGS: This study
      used the Behavior Assessment System for Children (BASC-2) to collect data on
      thirty-six 9-12 year old school-attending children's behavioral profiles in an
      Schistosoma mansoni-endemic area of western Kenya, before and after treatment
      with praziquantel for S. mansoni infection. BASC-2 T scores were significantly
      reduced post-treatment (p < 0.05) for each of the 'negative' behavior categories
      including externalizing problems (hyperactivity, aggression, and conduct problems
      that are disruptive in nature), internalizing problems (anxiety, depression,
      somatization, atypicality, and withdrawal), school problems (academic
      difficulties, included attention problems and learning problems), and the
      composite behavioral symptoms index (BSI), signifying improved behavior. While
      the observed improvement in the 'positive' behavior category of adaptive skills
      (adaptability, functional communication, social skills, leadership, and study
      skills) was not statistically significant, there were significant improvements in
      two adaptive skills subcategories: social skills and study skills.
      CONCLUSION/SIGNIFICANCE: Results of this study suggest that children have better
      school-related behaviors without heavy S. mansoni infection, and that infected
      children's behaviors, especially disruptive problem behaviors, improve
      significantly after praziquantel treatment.

PMID- 28746404
TI  - Pitx1 determines characteristic hindlimb morphologies in cartilage micromass
      culture.
AB  - The shapes of homologous skeletal elements in the vertebrate forelimb and
      hindlimb are distinct, with each element exquisitely adapted to their divergent
      functions. Many of the signals and signalling pathways responsible for patterning
      the developing limb bud are common to both forelimb and hindlimb. How disparate
      morphologies are generated from common signalling inputs during limb development
      remains poorly understood. We show that, similar to what has been shown in the
      chick, characteristic differences in mouse forelimb and hindlimb cartilage
      morphology are maintained when chondrogenesis proceeds in vitro away from the
      endogenous limb bud environment. Chondrogenic nodules that form in high-density
      micromass cultures derived from forelimb and hindlimb buds are consistently
      different in size and shape. We described analytical tools we have developed to
      quantify these differences in nodule morphology and demonstrate that
      characteristic hindlimb nodule morphology is lost in the absence of the hindlimb
      restricted limb modifier gene Pitx1. Furthermore, we show that ectopic expression
      of Pitx1 in the forelimb is sufficient to generate nodule patterns characteristic
      of the hindlimb. We also demonstrate that hindlimb cells are less adhesive to the
      tissue culture substrate and, within the limb environment, to the extracellular
      matrix and to each other. These results reveal autonomously programmed
      differences in forelimb and hindlimb cartilage precursors of the limb skeleton
      are controlled, at least in part, by Pitx1 and suggest this has an important role
      in generating distinct limb-type morphologies. Our results demonstrate that the
      micromass culture system is ideally suited to study cues governing morphogenesis
      of limb skeletal elements in a simple and experimentally tractable in vitro
      system that reflects in vivo potential.

PMID- 28746405
TI  - Biophysical characterization of the calmodulin-like domain of Plasmodium
      falciparum calcium dependent protein kinase 3.
AB  - Calcium dependent protein kinases are unique to plants and certain parasites and
      comprise an N-terminal segment and a kinase domain that is regulated by a C
      terminal calcium binding domain. Since the proteins are not found in man they are
      potential drug targets. We have characterized the calcium binding lobes of the
      regulatory domain of calcium dependent protein kinase 3 from the malaria parasite
      Plasmodium falciparum. Despite being structurally similar, the two lobes differ
      in several other regards. While the monomeric N-terminal lobe changes its
      structure in response to calcium binding and shows global dynamics on the sub
      millisecond time-scale both in its apo and calcium bound states, the C-terminal
      lobe could not be prepared calcium-free and forms dimers in solution. If our
      results can be generalized to the full-length protein, they suggest that the C
      terminal lobe is calcium bound even at basal levels and that activation is caused
      by the structural reorganization associated with binding of a single calcium ion
      to the N-terminal lobe.

PMID- 28746406
TI  - Multiple approaches to understanding the taxonomic status of an enigmatic new
      scorpion species of the genus Tityus (Buthidae) from the biogeographic island of
      Paraje Tres Cerros (Argentina).
AB  - Tityus curupi n. sp., belonging to the bolivianus complex, is described from the
      biogeographically distinct area of Paraje Tres Cerros in north-eastern Argentina.
      We also present a molecular species delimitation analysis between Tityus curupi
      n. sp. and its sister species Tityus uruguayensis Borelli 1901 to confirm species
      integrity. Furthermore, a cytogenetic analysis is presented for these two species
      which contain different multivalent associations in meiosis, as a consequence of
      chromosome rearrangements, and the highest chromosome numbers in the genus.

PMID- 28746407
TI  - Prehistoric mitochondrial DNA of domesticate animals supports a 13th century
      exodus from the northern US southwest.
AB  - The 13th century Puebloan depopulation of the Four Corners region of the US
      Southwest is an iconic episode in world prehistory. Studies of its causes, as
      well as its consequences, have a bearing not only on archaeological method and
      theory, but also social responses to climate change, the sociology of social
      movements, and contemporary patterns of cultural diversity. Previous research has
      debated the demographic scale, destinations, and impacts of Four Corners
      migrants. Much of this uncertainty stems from the substantial differences in
      material culture between the Four Corners vs. hypothesized destination areas.
      Comparable biological evidence has been difficult to obtain due to the complete
      departure of farmers from the Four Corners in the 13th century CE and
      restrictions on sampling human remains. As an alternative, patterns of genetic
      variation among domesticated species were used to address the role of migration
      in this collapse. We collected mitochondrial haplotypic data from dog (Canis
      lupus familiaris) and turkey (Meleagris gallopavo) remains from archaeological
      sites in the most densely-populated portion of the Four Corners region, and the
      most commonly proposed destination area for that population under migration
      scenarios. Results are consistent with a large-scale migration of humans,
      accompanied by their domestic turkeys, during the 13th century CE. These results
      support scenarios that suggest contemporary Pueblo peoples of the Northern Rio
      Grande are biological and cultural descendants of Four Corners populations.

PMID- 28746408
TI  - Microwave & magnetic proteomics of macrophages from patients with HIV-associated
      cognitive impairment.
AB  - OBJECTIVE: HIV-infected monocytes can infiltrate the blood brain barrier as
      differentiated macrophages to the central nervous system, becoming the primary
      source of viral and cellular neurotoxins. The final outcome is HIV-associated
      cognitive impairment (HACI), which remain prevalent today, possibly due to the
      longer life-span of the patients treated with combined anti-retroviral therapy.
      Our main goal was to characterize the proteome of monocyte-derived macrophages
      (MDM) from HACI patients, and its association with their cognitive status, to
      find novel targets for therapy. METHODS: MDM were isolated from the peripheral
      blood of 14 HIV-seropositive women characterized for neurocognitive function,
      including: four normal cognition (NC), five asymptomatic (A), and five with
      cognitive impaired (CI). Proteins from macrophage lysates were isobaric-labeled
      with the microwave and magnetic (M2) sample preparation method followed by liquid
      chromatography-tandem mass spectrometry-based protein identification and
      quantification. Differences in protein abundance across groups classified by HACI
      status were determined using analysis of variance. RESULTS: A total of 2,519
      proteins were identified with 2 or more peptides and 28 proteins were quantified
      as differentially expressed. Statistical analysis revealed increased abundance of
      17 proteins in patients with HACI (p<0.05), including several enzymes associated
      to the glucose metabolism. Western blot confirmed increased expression of 6
      Phosphogluconate dehydrogenase and L-Plastin in A and CI patients over NC and HIV
      seronegatives. CONCLUSIONS: This is the first quantitative proteomics study
      exploring the changes in protein abundance of macrophages isolated from patients
      with HACI. Further studies are warranted to determine if these proteins may be
      target candidates for therapy development against HACI.

PMID- 28746409
TI  - High resolution molecular and histological analysis of renal disease progression
      in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy.
AB  - ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and
      diabetes, and have gained interest as a model system with potentially high
      translational value to progressive human disease. To thoroughly characterize this
      model, and to better understand how closely it recapitulates human disease, we
      performed a high resolution longitudinal analysis of renal disease progression in
      ZSF1 rats spanning from early disease to end stage renal disease. Analyses
      included metabolic endpoints, renal histology and ultrastructure, evaluation of a
      urinary biomarker of fibrosis, and transcriptome analysis of glomerular-enriched
      tissue over the course of disease. Our findings support the translational value
      of the ZSF1 rat model, and are provided here to assist researchers in the
      determination of the model's suitability for testing a particular mechanism of
      interest, the design of therapeutic intervention studies, and the identification
      of new targets and biomarkers for type 2 diabetic nephropathy.

PMID- 28746410
TI  - Environmental factors influencing the spatio-temporal distribution of Carybdea
      marsupialis (Lineo, 1978, Cubozoa) in South-Western Mediterranean coasts.
AB  - Jellyfish blooms cause important ecological and socio-economic problems. Among
      jellyfish, cubozoans are infamous for their painful, sometimes deadly, stings and
      are a major public concern in tropical to subtropical areas; however, there is
      little information about the possible causes of their outbreaks. After a bloom of
      the cubomedusa Carybdea marsupialis (Carybdeidae) along the coast of Denia (SW
      Mediterranean, Spain) in 2008 with negative consequences for local tourism, the
      necessity to understand the ecological restrictions on medusae abundance was
      evident. Here we use different models (GAM and zero-inflated models) to
      understand the environmental and human related factors influencing the abundance
      and distribution of C. marsupialis along the coast of Denia. Selected variables
      differed among medusae size classes, showing different environmental restriction
      associated to the developmental stages of the species. Variables implicated with
      dispersion (e.g. wind and current) affected mostly small and medium size classes.
      Sea surface temperature, salinity and proxies of primary production (chl a,
      phosphates, nitrates) were related to the abundances of small and large size
      classes, highlighting the roles of springtime salinity changes and increased
      primary production that may promote and maintain high densities of this species.
      The increased primary (and secondary) production due to anthropogenic impact is
      implicated as the factor enabling high numbers of C. marsupialis to thrive.
      Recommendations for monitoring blooms of this species along the study area and
      applicable to Mediterranean Sea include focus effort in coastal waters where
      productivity have been enriched by anthropogenic activities.

PMID- 28746411
TI  - Selection and validation of reference genes for quantitative real-time PCR
      analysis under different experimental conditions in the leafminer Liriomyza
      trifolii (Diptera: Agromyzidae).
AB  - Liriomyza trifolii is a highly-invasive leafmining insect that causes significant
      damage to vegetables and horticultural crops worldwide. Relatively few studies
      have quantified gene expression in L. trifolii using real-time quantitative PCR
      (RT-qPCR), which is a reliable and sensitive technique for measuring gene
      expression. RT-qPCR requires the selection of reference genes to normalize gene
      expression data and control for internal differences between samples. In this
      study, nine housekeeping genes from L. trifolii were selected for their
      suitability in normalizing gene expression using geNorm, Normfinder, BestKeeper,
      the DeltaCt method and RefFinder. HSP21.7, which encodes heat shock protein 21.7,
      was used as a target gene to validate the expression of candidate reference
      genes. Results indicated that ACTIN and 18S were optimal for developmental stage
      and low temperature, TUB and 18S showed the most stable expression for sex, and
      GAPDH and ACTIN were the best reference genes for monitoring gene expression at
      high temperature. Selection and validation of appropriate reference genes are
      critical steps in normalizing gene expression levels, which improve the accuracy
      and quality of expression data. Results of this study provide vital information
      on reference genes and is valuable in developing a standardized RT-qPCR protocol
      for functional genomics research in L. trifolii.

PMID- 28746412
TI  - The enemy as animal: Symmetric dehumanization during asymmetric warfare.
AB  - Historically, dehumanization has enabled members of advantaged groups to 'morally
      disengage' from disadvantaged group suffering, thereby facilitating acts of
      intergroup aggression such as colonization, slavery and genocide. But is blatant
      dehumanization exclusive to those at the top 'looking down', or might
      disadvantaged groups similarly dehumanize those who dominate them? We examined
      this question in the context of intergroup warfare in which the disadvantaged
      group shoulders a disproportionate share of casualties and may be especially
      likely to question the humanity of the advantaged group. Specifically, we
      assessed blatant dehumanization in the context of stark asymmetric conflict
      between Israelis (Study 1; N = 521) and Palestinians (Study 2; N = 354) during
      the 2014 Gaza war. We observed that (a) community samples of Israelis and
      Palestinians expressed extreme (and comparable) levels of blatant dehumanization,
      (b) blatant dehumanization was uniquely associated with outcomes related to
      outgroup hostility for both groups, even after accounting for political
      ideologies known to strongly predict outgroup aggression, and (c) the strength of
      association between blatant dehumanization and outcomes was similar across both
      groups. This study illuminates the striking potency and symmetry of blatant
      dehumanization among those on both sides of an active asymmetric conflict.

PMID- 28746413
TI  - Insomnia with objective short sleep duration is associated with longer duration
      of insomnia in the Freiburg Insomnia Cohort compared to insomnia with normal
      sleep duration, but not with hypertension.
AB  - STUDY OBJECTIVES: To replicate the association between insomnia with objective
      short sleep duration and hypertension, type 2 diabetes and duration of insomnia.
      DESIGN: Retrospective case-control study. SETTING: Department of Psychiatry and
      Psychotherapy, Medical Center-University of Freiburg. PARTICIPANTS: 328 patients
      with primary insomnia classified according to DSM-IV criteria (125 males, 203
      females, 44.3 +/- 12.2 years). INTERVENTIONS: N/A. MEASUREMENTS: All participants
      were investigated using polysomnography, blood pressure measurements, and fasting
      routine laboratory. RESULTS: Insomnia patients with short sleep duration (< 6
      hours) in the first night of laboratory sleep presented with a longer duration of
      insomnia compared to those with normal sleep duration (>= 6 hours) in the first
      night of laboratory sleep. Insomnia patients who were categorised as short
      sleepers in either night were not more likely to suffer from hypertension
      (systolic blood pressure of >= 140 mm Hg, diastolic blood pressure of >= 90 mm
      Hg, or a previously established diagnosis). Data analysis showed that insomnia
      patients with objective short sleep duration were not more likely to suffer from
      type 2 diabetes (fasting plasma glucose level of >= 126 mg/dl, or a previously
      established diagnosis). However, the diabetes analysis was only based on a very
      small number of diabetes cases. As a new finding, insomnia patients who were
      categorised as short sleepers in either night presented with increases in liver
      enzyme levels. CONCLUSIONS: The finding on insomnia duration supports the concept
      of two distinct sub-groups of insomnia, namely insomnia with, and without,
      objectively determined short sleep duration. However, our data challenges
      previous findings that insomnia patients with short sleep duration are more
      likely to suffer from hypertension.

PMID- 28746414
TI  - When habitat matters: Habitat preferences can modulate co-occurrence patterns of
      similar sympatric species.
AB  - Disentangling the role of competition in regulating the distribution of sympatric
      species can be difficult because species can have different habitat preferences
      or time use that introduce non-random patterns that are not related to
      interspecific interactions. We adopted a multi-step approach to systematically
      incorporate habitat preferences while investigating the co-occurrence of two
      presumed competitors, morphologically similar, and closely related ground
      dwelling birds: the brown tinamou (Crypturellus obsoletus) and the tataupa
      tinamou (C. tataupa). First, we used single-species occupancy models to identify
      the main landscape characteristics affecting site occupancy, while accounting for
      detection probability. We then used these factors to control for the effect of
      habitat while investigating species co-occurrence. In addition, we investigated
      species present-time partitioning by measuring the degree of overlap in their
      activity time. Both species were strictly diurnal and their activity time highly
      overlapped (i.e., the species are not present-time partitioning). The
      distribution of the two species varied across the landscape, and they seemed to
      occupy opposite portions of the study area, but co-occurrence models and species
      interaction factors suggested that the tinamous have independent occupancy and
      detection. In addition, co-occurrence models that accounted for habitat performed
      better than models without habitat covariates. The observed co-occurrence pattern
      is more likely related to habitat preferences, wherein species segregated by
      elevation. These results provide evidence that habitat characteristics can play a
      bigger role than interspecific interactions in regulating co-existence of some
      species. Therefore, exploring habitat preferences while analyzing co-occurrence
      patterns is essential, in addition to being a feasible approach to achieve more
      accurate estimation of parameters reflecting species interactions. Occupancy
      models can be a valuable tool in such modeling.

PMID- 28746415
TI  - The potential dysfunction of otolith organs in patients after mumps infection.
AB  - OBJECTIVE: To investigate the relationship between mumps and the extent of
      hearing impairment and otolith organ damage. METHODS: A total of 27 patients with
      unilateral hearing impairment following mumps were enrolled. The degrees of
      hearing loss and otolith organ damage were confirmed by audiometric and
      vestibular evoked myogenic potential [VEMP] tests. All the results were compared
      and analyzed using Stata 13.0 software for Windows. RESULTS: The VEMP thresholds
      of the affected ears were significantly higher than those of the unaffected ears
      in both tests (cervical VEMP [cVEMP] test and ocular VEMP [oVEMP] test; p = 0.000
      and 0.001, respectively). The mean cVEMP and oVEMP threshold values of the
      affected ears with hearing impairment for <=10 years were significantly lower
      than those of affected ears with hearing impairment for >10 years [p = 0.009 and
      0.004, respectively]. CONCLUSIONS: Deafness resulting from mumps is usually
      profound and permanent, which indicates severe damage to the cochlea due to the
      disease. The functions of otolith organs in the vestibular system are also
      impaired. Over time, the function of the otolith organs or their neural pathway
      may suffer secondary damage.

PMID- 28746416
TI  - Temporal dynamics of ovine airway epithelial cell differentiation at an air
      liquid interface.
AB  - The respiratory tract and lungs are subject to diverse pathologies with wide
      ranging implications for both human and animal welfare. The development and
      detailed characterization of cell culture models for studying such forms of
      disease is of critical importance. In recent years the use of air-liquid
      interface (ALI)-cultured airway epithelial cells has increased markedly, as this
      method of culture results in the formation of a highly representative,
      organotypic in vitro model system. In this study we have expanded on previous
      knowledge of differentiated ovine tracheal epithelial cells by analysing the
      progression of differentiation over an extensive time course at an ALI. We
      observed a pseudo-stratified epithelium with ciliation and a concurrent increase
      in cell layer thickness from 9 days post-ALI with ciliation approaching a maximum
      level at day 24. A similar pattern was observed with respect to mucus production
      with intensely stained PAS-positive cells appearing at day 12. Ultrastructural
      analysis by SEM confirmed the presence of both ciliated cells and mucus globules
      on the epithelial surface within this time-frame. Trans-epithelial electrical
      resistance (TEER) peaked at 1049 Omega * cm2 as the cell layer became confluent,
      followed by a subsequent reduction as differentiation proceeded and stabilization
      at ~200 Omega * cm2. Importantly, little deterioration or de-differentiation was
      observed over the 45 day time-course indicating that the model is suitable for
      long-term experiments.

PMID- 28746417
TI  - Immunological and inflammatory mapping of vascularized composite allograft
      rejection processes in a rat model.
AB  - BACKGROUND: Hand and face vascularized composite allotransplantation (VCA) is an
      evolving and challenging field with great opportunities. During VCA, massive
      surgical damage is inflicted on both donor and recipient tissues, which may
      contribute to the high VCA rejection rates. To segregate between the damage
      induced and rejection phase of post-VCA responses, we compared responses
      occurring up to 5 days following syngeneic versus allogeneic vascularized groin
      flap transplantations, culminating in transplant acceptance or rejection,
      respectively. METHODS: The immune response elicited upon transplantation of a
      syngeneic versus allogeneic vascularized groin flap was compared at Post
      operative days 2 or 5 by histology, immunohistochemistry and by broad-scope gene
      and protein analyses using quantitative real-time PCR and Multiplex respectively.
      RESULTS: Immune cell infiltration began at the donor-recipient interface and
      paralleled expression of a large group of wound healing-associated genes in both
      allografts and syngrafts. By day 5 post-transplantation, cell infiltration spread
      over the entire allograft but remained confined to the wound site in the
      syngraft. This shift correlated with upregulation of IL-18, INFg, CXCL9, 10 and
      11, CCL2, CCL5, CX3CL1 and IL-10 in the allograft only, suggesting their role in
      the induction of the anti-alloantigen adaptive immune response. CONCLUSIONS: High
      resemblance between the cues governing VCA and solid organ rejection was
      observed. Despite this high resemblance we describe also, for the first time, a
      damage induced inflammatory component in VCA rejection as immune cell
      infiltration into the graft initiated at the surgical damage site spreading to
      the entire allograft only at late stage rejection. We speculate that the highly
      inflammatory setting created by the unique surgical damage during VCA may enhance
      acute allograft rejection.

PMID- 28746418
TI  - A user-friendly, low-cost turbidostat with versatile growth rate estimation based
      on an extended Kalman filter.
AB  - For various experimental applications, microbial cultures at defined, constant
      densities are highly advantageous over simple batch cultures. Due to high costs,
      however, devices for continuous culture at freely defined densities still
      experience limited use. We have developed a small-scale turbidostat for research
      purposes, which is manufactured from inexpensive components and 3D printed parts.
      A high degree of spatial system integration and a graphical user interface
      provide user-friendly operability. The used optical density feedback control
      allows for constant continuous culture at a wide range of densities and offers to
      vary culture volume and dilution rates without additional parametrization.
      Further, a recursive algorithm for on-line growth rate estimation has been
      implemented. The employed Kalman filtering approach based on a very general state
      model retains the flexibility of the used control type and can be easily adapted
      to other bioreactor designs. Within several minutes it can converge to robust,
      accurate growth rate estimates. This is particularly useful for directed
      evolution experiments or studies on metabolic challenges, as it allows direct
      monitoring of the population fitness.

PMID- 28746419
TI  - Glass import and production in Hispania during the early medieval period: The
      glass from Ciudad de Vascos (Toledo).
AB  - One hundred and forty-one glass fragments from medieval Ciudad de Vascos (Toledo,
      Spain) were analysed by laser ablation inductively coupled plasma mass
      spectrometry (LA-ICP-MS). The glasses fall into three types according to the
      fluxing agents used: mineral natron, soda-rich plant ash, and a combination of
      soda ash and lead. The natron glasses can be assigned to various established
      primary production groups of eastern Mediterranean provenance. Different types of
      plant ash glasses indicate differences in the silica source as well as the plant
      ash component, reflecting changing supply mechanisms. While the earlier plant ash
      groups can be related to Islamic glasses from the Near East, both in terms of
      typology and composition, the chemical signature of the later samples appear to
      be specific to glass from the Iberian Peninsula. This has important implications
      for our understanding of the emerging glass industry in Spain and the
      distribution patterns of glass groups and raw materials. The plant ash that was
      used for the Vascos glasses is rich in soda with low levels of potash, similar to
      ash produced in the eastern Mediterranean. It could therefore be possible that
      Levantine plant ash was imported and used in Islamic period glass workshops in
      Spain. Unlike central and northern Europe where an independent glass industry
      based on potassium-rich wood ash developed during the Carolingian period, the
      prevalence of soda ash and soda ash lead glass on the Iberian Peninsula indicates
      its commercial and technological interconnection with the Islamic east. Our study
      thus traces several stages leading to the development of a specifically Spanish
      primary glassmaking industry.

PMID- 28746420
TI  - Compositional changes in bee and wasp communities along Neotropical mountain
      altitudinal gradient.
AB  - Climate conditions tend to differ along an altitudinal gradient, resulting in
      some species groups' patterns of lower species richness with increasing altitude.
      While this pattern is well understood for tropical mountains, studies
      investigating possible determinants of variation in beta-diversity at its
      different altitudes are scarce. We sampled bee and wasp communities (Hymenoptera:
      Aculeata) along an altitudinal gradient (1,000-2,000 m.a.s.l.) in a tropical
      mountainous region of Brazil. Trap nests and Moericke traps were established at
      six sampling points, with 200 m difference in altitude between each point. We
      obtained average climate data (1970-2000) from Worldclim v2 for altitudes at each
      sampling site. Nest traps captured 17 bee and wasp species from six families, and
      Moericke traps captured 124 morphospecies from 13 families. We found a negative
      correlation between altitude and species richness and abundance. Temperature,
      precipitation, water vapor pressure, and wind speed influenced species richness
      and abundance, and were correlated with altitude. beta-diversity was primarily
      determined by species turnover as opposed to nestedness, and Aculeate community
      similarity was higher for more similar altitudinal ranges. Moericke traps seem to
      be more efficient for altitudinal surveys compared to nest traps. We found high
      occurrence of singleton and doubleton species at all altitudes, highlighting the
      need for long-term studies to efficiently assess hymenopteran diversity in these
      environments.

PMID- 28746421
TI  - Developmental changes in the levels and redox potentials of main hemolymph
      thiols/disulfides in the Jamaican field cricket Gryllus assimilis.
AB  - Main thiols and disulfides were determined in the hemolymph of the Jamaican field
      cricket Gryllus assimilis at various developmental stages. On the basis of these
      data, redox potentials of the glutathione, cysteine and homocysteine redox
      systems were calculated. The concentrations of all thiols studied decreased
      during development (at a stage of 6 molts) with respect to young crickets, and
      increased again in adult insects. Redox potentials of the glutathione and
      cysteine systems increased from values of -131.0+/-5.6 mV and -86.9+/-17.1 mV,
      respectively in young crickets to -58.0+/-3.6 mV and -36.1+/-4.2 mV,
      respectively, at the stage of 6 molts and decreased to values of -110.4+/-24.8 mV
      and -66.3+/-12.2 mV, respectively, in adult insects. Redox potentials of the
      glutathione and cysteine systems in the hemolymph of young and adult insects were
      similar to those reported for human plasma.

PMID- 28746422
TI  - Patients with Duchenne and Becker muscular dystrophies are not more asymmetrical
      than healthy controls on timed performance of upper limb tasks.
AB  - This study aimed to investigate possible asymmetries and relationships between
      performance of dominant and non-dominant upper limbs (UL) in patients with
      Duchenne and Becker muscular dystrophies (DMD/BMD), to compare UL performance of
      patients and healthy subjects and to investigate the relationship between timed
      performance of UL and age, motor function and muscle strength in DMD/BMD
      patients. Sixteen patients with DMD and 3 with BMD were evaluated with Jebsen
      Taylor Test (timed performance), Vignos scale and Dimension 3 of Motor Function
      Measure (motor function), and Medical Research Council scale (muscle strength) on
      a single session. ANOVA showed no asymmetry between dominant and non-dominant UL,
      except in the writing subtest, in patients and in healthy controls. There were
      relationships between dominant and non-dominant UL performances. Correlations
      between timed performance, motor function and muscle strength were found, but age
      was not correlated with these variables. These findings may reduce the assessment
      time, prevent fatigue and provide more accurate clinical reasoning involving UL
      in DMD/BMD treatment.

PMID- 28746423
TI  - Following the road of progress in acute ischemic stroke care.

PMID- 28746424
TI  - Craniocervical junction abnormalities in northeast Brazilian population.

PMID- 28746425
TI  - The direct first pass aspiration technique in the treatment of acute ischemic
      stroke resulting from large vessel occlusions.
AB  - Methods: Recanalization was assessed using the modified thrombolysis in cerebral
      infarction (mTICI) score. Neurological outcomes were assessed using the National
      Institutes of Health Stroke Scale and modified Rankin Scale. Results: Fifteen
      patients were evaluated. The mTICI score was 2b-3 in 80%, and it was 3 in 60% of
      patients. No intracranial hemorrhage was seen. At three months, modified Rankin
      Scale scores <= 2 were observed in 60% of patients and the mortality rate was
      13.3%. Conclusions: The ADAPT appears to be a safe, effective, and fast
      recanalization strategy for treatment of acute ischemic stroke resulting from
      large vessel occlusions.

PMID- 28746426
TI  - Cranio-vertebral transition assessment by magnetic resonance imaging in a sample
      of a northeast Brazilian population.
AB  - Methods: Cross-sectional analysis of craniometric parameters from individuals
      submitted to magnetic resonance at an outpatient imaging center between 2011 and
      2012. Results: Of 181 analyzed cases, the Welcker basal angle averaged 128.96o
      (SD 6.51), median distance between apex of the odontoid and Chamberlain's line
      was 2.27 mm (IQR -1.23-4.47) and the median clivus-canal angle was 150.5o (IQR
      143.2-157.3). The Welcker basal angle was inversely correlated to the clivus
      canal angle, and correlated to the distance between the apex of the odontoid and
      Chamberlain's line. Conclusion: There was a tendency to platibasia, basilar
      invagination and narrowing of the cranio-vertebral transition.

PMID- 28746427
TI  - Decompressive craniotomy for the treatment of malignant infarction of the middle
      cerebral artery: mortality and outcome.
AB  - Objective: To assess, by Rankin scale, the functional disability of patients who
      had a malignant middle cerebral artery (MCA) ischemic stroke, who underwent
      decompressive craniotomy (DC) within the first 30 days. Methods: A cross
      sectional study in a University hospital. Between June 2007 and December 2014, we
      retrospectively analyzed the records of all patients submitted to DC due to a
      malignant MCA infarction. The mortality rate was defined during the
      hospitalization period. The modified outcome Rankin score (mRS) was measured 30
      days after the procedure, for stratification of the quality of life. Results: The
      DC mortality rate was 30% (95% CI 14.5 to 51.9) for the 20 patients reported. The
      mRS 30 days postoperatively was >= 4 [3.3 to 6] for all patients thereafter.
      Conclusion: DC is to be considered a real alternative for the treatment of
      patients with a malignant ischemic MCA infarction.

PMID- 28746428
TI  - The association of the circle of Willis anomaly and risk of stroke in patients
      with carotid artery disease.
AB  - Results: In this retrospective study, we analyzed 175 patients who presented at
      our outpatient stroke clinic between January, 2013 and June, 2015 with either
      unilateral symptomatic or asymptomatic carotid artery disease, and who had had CT
      angiography imaging performed. Demographic properties, carotid artery stenosis
      and the anomaly of the circle of Willis was recorded. Conclusion: There was no
      statistically significant difference in patients with symptomatic and
      asymptomatic carotid artery disease in terms of the anomaly of the circle of
      Willis.

PMID- 28746429
TI  - Cerebrospinal fluid drainage options for posthemorrhagic hydrocephalus in
      premature neonates.
AB  - Objective: The literature describes various cerebrospinal fluid (CSF) drainage
      techniques to alleviate posthemorrhagic hydrocephalus in preterm newborns;
      however, consensus has not been reached. The scope of this study was describing a
      case series of premature neonates with posthemorrhagic hydrocephalus and
      assessing the outcomes of different approaches used for CSF diversion. Methods: A
      consecutive review of the medical records of neonates with posthemorrhagic
      hydrocephalus treated with CSF drainage was conducted. Results: Forty premature
      neonates were included. Serial lumbar puncture, ventriculosubgaleal shunt, and
      ventriculoperitoneal shunt were the treatments of choice in 25%, 37.5% and 37.5%
      of the cases, respectively. Conclusion: Cerebrospinal fluid diversion should be
      tailored to each case with preference given to temporary CSF drainage in neonates
      with lower age and lower birth-weight, while the permanent ventriculoperitoneal
      shunt should be considered in healthier, higher birth-weight neonates born closer
      to term.

PMID- 28746430
TI  - The intercostobrachial nerve as a sensory donor for hand reinnervation in
      brachial plexus reconstruction is a feasible technique and may be useful for
      restoring sensation.
AB  - Objective: Few donors are available for restoration of sensibility in patients
      with complete brachial plexus injuries. The objective of our study was to
      evaluate the anatomical feasibility of using the intercostobrachial nerve (ICBN)
      as an axon donor to the lateral cord contribution to the median nerve (LCMN).
      Methods: Thirty cadavers were dissected. Data of the ICBN and the LCMN were
      collected, including diameters, branches and distances. Results: The diameters of
      the ICBN and the LCMN at their point of coaptation were 2.7mm and 3.7mm,
      respectively. The ICBN originated as a single trunk in 93.3% of the specimens and
      bifurcated in 73.3%. The distance between the ICBN origin and its point of
      coaptation to the LCMN was 54mm. All ICBNs had enough extension to reach the
      LCMN. Conclusion: Transfer of the ICBN to the LCMN is anatomically feasible and
      may be useful for restoring sensation in patients with complete brachial plexus
      injuries.

PMID- 28746431
TI  - ID-MigraineTM questionnaire and accurate diagnosis of migraine.
AB  - Objective: To analyze the applicability of the Portuguese version of ID
      MigraineTM in a sample of Brazilian patients. Methods: Patients with headache
      were recruited from the neurology outpatient clinic of a tertiary hospital and
      submitted to the ID-MigraineTM questionnaire. The diagnosis of headache was made
      according to the ICHD-2 criteria. Results: Of the 232 patients, 86% had migraine.
      The questionnaire showed a sensitivity of 92% (95%CI, 88% to 95%), specificity of
      60% (95%CI, 43% to 77%) and a positive predictive value of 93% (95%CI, 89% to
      96%). Discussion: Our results were similar to other international studies of the
      ID-MigraineTM application. The Portuguese version is considered easy to use, and
      an appropriate screening tool for migraine diagnosis in our sample. Conclusion:
      Considering the characteristics of our health system, we can infer that this
      questionnaire would be beneficial in a Brazilian primary care setting; however,
      more studies are necessary.

PMID- 28746432
TI  - Late onset multiple sclerosis: concerns in aging patients.
AB  - Late onset multiple sclerosis (LOMS) is when the first symptom starts after 50
      years of age, representing 4.5% of multiple sclerosis (MS) patients. This study
      describes the clinical characteristics of patients with LOMS followed at a
      specialized MS center in Sao Paulo. Data was obtained from medical records of 742
      patients with MS. The LOMS frequency was 4.18%, median age at onset was 54 years
      and the predominant disease course was primary progressive (64.3%). The patients
      reached the disability landmarks of EDSS grades 3.0, 6.0 and 7.0 in the following
      proportion and time: EDSS 3.0: 77.42% of patients in 3.7 years; EDSS 6.0: 58.06%
      in 5.1 years and EDSS 7.0: 32.26% in 5.7 years. The comparative analysis with a
      matched control group of patients with early onset MS showed that late onset,
      associated with a progressive course, were predictors of reaching EDSS 3.0 and
      6.0 in a shorter time.

PMID- 28746433
TI  - Quantitative Myasthenia Gravis Score: a Brazilian multicenter study for
      translation, cultural adaptation and validation.
AB  - Objective: To perform the translation, cross-cultural adaptation and validation
      of the Quantitative Myasthenia Gravis Score (QMGS) to Brazilian Portuguese in
      accordance with international ethical standards. Methods: The following steps
      were taken: (1) implementation of the translation protocol and transcultural
      adaptation, (2) validation of the adapted content, and (3) assessment of
      reliability. To check intra- and inter-observer reproducibility, each patient
      underwent two interviews with interviewer-A and one with B. The QMGS was compared
      to the Myasthenia Gravis Composite Scale and Myasthenia-specific Quality of Life
      Questionnaire. Results: Our study group consisted of 30 patients, with a mean age
      of 47.6+/-11.4 years and a mean duration of illness of 11.33+/-8.49 years.
      Correlation between the QMGS and MGC was very strong (r = 0.928; p < 0.001) and
      substantial between the QMGS and MG-QOL 15 (r = 0.737; p < 0.001). Conclusion:
      The Brazilian Portuguese translation, and validation of the QMGS was successfully
      performed.

PMID- 28746434
TI  - Critical analysis on the present methods for brain volume measurements in
      multiple sclerosis.
AB  - Objective: The treatment of multiple sclerosis (MS) has quickly evolved from a
      time when controlling clinical relapses would suffice, to the present day, when
      complete disease control is expected. Measurement of brain volume is still at an
      early stage to be indicative of therapeutic decisions in MS. Methods: This paper
      provides a critical review of potential biases and artifacts in brain measurement
      in the follow-up of patients with MS. Results: Clinical conditions (such as
      hydration or ovulation), time of the day, type of magnetic resonance machine
      (manufacturer and potency), brain volume artifacts and different platforms for
      volumetric assessment of the brain can induce variations that exceed the
      acceptable physiological rate of annual loss of brain volume. Conclusion:
      Although potentially extremely valuable, brain volume measurement still has to be
      regarded with caution in MS.

PMID- 28746435
TI  - Cerebral hemodynamic and metabolic changes in fulminant hepatic failure.
AB  - Intracranial hypertension and brain swelling are a major cause of morbidity and
      mortality of patients suffering from fulminant hepatic failure (FHF). The
      pathogenesis of these complications has been investigated in man, in experimental
      models and in isolated cell systems. Currently, the mechanism underlying cerebral
      edema and intracranial hypertension in the presence of FHF is multi-factorial in
      etiology and only partially understood. The aim of this paper is to review the
      pathophysiology of cerebral hemodynamic and metabolism changes in FHF in order to
      improve understanding of intracranial dynamics complication in FHF.

PMID- 28746436
TI  - Effect of intra-hippocampal injection of human recombinant growth hormone on
      synaptic plasticity in the nucleus basalis magnocellularis-lesioned aged rats.
AB  - In this study, we proposed that administration of hippocampal growth hormone in
      ageing animals with growth hormone deficiency can compensate long-term
      potentiation and synaptic plasticity in nucleus basalis magnocellularis (NBM)
      lesioned rats. Aged male Wistar rats were randomly divided into six groups (seven
      in each) of sham-operated healthy rats (Cont); NBM-lesioned rats (L); NBM
      lesioned rats and intrahippocampal injection of growth hormone vehicle (L + Veh);
      NBM-lesioned and intrahippocampal injection of growth hormone (10, 20 and 40 ug.2
      ul-1) (L + GH). In vivo electrophysiological recording techniques were used to
      characterize maintenance of long-term potentiation at distinct times (1, 2, 3, 24
      and 48 hours) after high-frequency stimulation. The population spike was enhanced
      significantly for about 48 hours following tetanic stimulation in rats treated
      with a dose-dependent growth hormone compared to the vehicle group (p < 0.05),
      possibly through neuronal plasticity and neurogenesis in affected areas.

PMID- 28746437
TI  - The art and neurology of Paul Richer.
AB  - In the 1890s, one of Charcot's most important proteges, Dr. Paul Richer (1849
      1933), drew and sculpted a series of representations of the main types of nerve
      pathology. That series included drawings of pleomorphic hysterical crises and
      sculptures depicting patients suffering from labio-glosso-laryngeal paralysis and
      myopathy, as well as Parkinson's disease. Richer was a resident at La Salpetriere
      and, in 1882, became head of the Charcot museum. Early in his career, despite
      having no formal artistic training, he could represent masterfully, in drawings
      and sculptures, people's tragic suffering from neurological diseases. Later on,
      with the same tools, he expressed the beauty of human movements in health.

PMID- 28746438
TI  - Magnetic resonance findings in subacute combined degeneration.

PMID- 28746439
TI  - Acute Epstein-Barr virus encephalitis in an immunocompetent adolescent patient.

PMID- 28746440
TI  - Burning pain attacks and red skin in a young woman.

PMID- 28746441
TI  - Economic evaluation and efficacy of strategic-selective treatment of
      gastrointestinal parasites in dairy calves.
AB  - In the Experimental Farm of the Universidade Federal de Lavras (EF-UFLA), state
      of Minas Gerais, Brazil, on their day of birth, female Holstein calves were
      randomly selected and placed into two groups containing fifteen animals each:
      Strategic-Selective Treatment (S-ST) or Conventional Treatment (CT). In the S-ST,
      calves were treated after coproparasitological examinations according to criteria
      established previously by the researchers. Calves in the CT were treated
      according to the opinion of the veterinarian of EF-UFLA. For statistical
      analysis, the frequency (%) of fecal samples with count of eggs per gram of feces
      (EPG) >=300, count of oocysts per gram of feces (OoPG) >=500 and fecal samples
      with count of cysts of Giardia spp. >=1 were conducted. The overall average
      frequency of fecal samples with EPG >=300, OoPG >=500 and Giardia spp. cysts >=1,
      respectively, was similar (p >0.05) between S-ST (20.3%; 17.3%; and 31.5%) and CT
      (26.4%; 23.9%; and 37.3%). The effective operational cost, per animal, in 12
      months, was of R$ 784.58 (US$ 241.41) and R$ 83.90 (US$ 25.81) in S-ST and CT,
      respectively. The S-ST requires adjustments to be used as a technically efficient
      and economically viable alternative for the control of gastrointestinal
      parasitosis in female Holstein calves.

PMID- 28746442
TI  - Parasitic survey on introduced monk parakeets (Myiopsitta monachus) in Santiago,
      Chile.
AB  - Central Chile has been identified as a unique ecosystem with high conservation
      priority because of its high levels of endemism and intensive anthropic pressure.
      Over a period of almost four decades, the monk parakeet has been successful in
      establishing and dispersing in urban Santiago, although little is known about its
      potential impact. Furthermore, nothing is known about its epidemiological risks
      towards animals or even humans. For this reason, we conducted the first parasitic
      survey of monk parakeets in Chile through capture, necropsy and thorough external
      and internal inspection of 92 adult individuals. Among these, 45.7% presented
      lice that were identified as Paragoniocotes fulvofasciatum, 1.1% had
      mesostigmatid acari and 8.9% had free-ranging acari. Among 89 parakeets, 19.1%
      had structures identified as Cryptosporidium sp. This study provides the first
      description of Cryptosporidium sp. in monk parakeets. Along with the presence of
      a mesostigmatid acarus in one parakeet, this serves as a public health warning,
      given that both of these parasites have zoonotic potential.

PMID- 28746443
TI  - Ectoparasites community in Satanoperca jurupari (Cichlidae) from the Jari River,
      a tributary from Amazon River in Northern Brazil.
AB  - The aim of this study was to investigate the gills parasites in Satanoperca
      jurupari from the Jari River, state of Amapa, in eastern Amazon (Brazil). The
      gills of 100% of the hosts were parasitized by Ichthyophthirius multifiliis
      (Protozoa), Sciadicleithrum juruparii (Monogenoidea) Genarchella genarchella,
      Posthodiplostomum sp. (Digenea) Ergasilus coatiarus and Argulus multicolor
      (Crustacea), and a total of 27,043 parasites were collected. However, the
      dominance was of I. multifiliis and there was aggregated dispersion of parasites
      with greater discrepancy for S. juruparii and A. multicolor. Low species richness
      of parasites (3.1 +/- 1.1), low Brillouin diversity index (0.27 +/- 0.23), low
      evenness (0.16 +/- 0.13) and high dominance of Berger-Parker (0.88 +/- 0.15) were
      found. The community of parasites in S. jurupari was characterized by low species
      richness, low diversity and low evenness, with high prevalence and low abundance.
      The size of host did not have any influence on the parasites community, but the
      host behavior and availability of infective stages of the parasites were factors
      structuring the community of ectoparasites found here.

PMID- 28746444
TI  - Metazoan parasites of Plagioscion squamosissimus, an invasive species in the
      Tiete River, Sao Paulo, Brazil.
AB  - This study focused on the characterization and analysis of communities and infra
      communities of metazoan parasites of Plagioscion squamosissimus caught in
      Promissao Reservoir in the Tiete River in Borborema (21 degrees 39'58"S, 49
      degrees 8'49"W), state of Sao Paulo, Brazil. Fifty adult specimens caught by
      professional fishermen in March 2015 were necropsied. The fish presented an
      average standard length of 25.2 +/- 2.2 cm and average weight of 328.82 +/- 89.03
      g. A total of 5,227 specimens of metazoan parasites were collected: 2,880 (55.1%)
      adult Diplectanum piscinarius (Monogenoidea: Diplectanidae) and 2,347 (44.9%)
      Austrodiplostomum compactum metacercariae (Digenea, Diplostomidae), both with
      100% prevalence and mean abundance of 57.6 and 46.9, respectively. Parasite
      diversity was low (species richness = 2), with a Simpson index (D) equal to
      0.505, and low values of Brillouin (HB = 0.687) and Margalef diversity (I =
      0.117) indices. Berger-Parker's index of dominance (p = 0.551) indicated a slight
      dominance of the monogenean parasite D. piscinarius. There was a positive
      correlation, assessed by Pearson coefficient between parasite abundance of D.
      piscinarius and standard length (r = 0.43) and weight (r = 0.51) of hosts.

PMID- 28746445
TI  - Bat trypanosomes from Tapajos-Arapiuns Extractive Reserve in Brazilian Amazon.
AB  - Trypanosoma comprises flagellates able to infect several mammalian species and is
      transmitted by several groups of invertebrates. The order Chiroptera can be
      infected by the subgenera Herpetosoma, Schizotrypanum, Megatrypanum and
      Trypanozoon. In this study, we described the diversity of bat trypanosomes and
      inferred phylogenetic relationships among the trypanosomes from bats caught in
      Tapajos-Arapiuns Extractive Reserve (Resex) in Para state. Trypanosomes from bats
      were isolated by means of hemoculture, and the molecular phylogeny was based on
      the trypanosome barcode (SSUrDNA V7V8 variable region). A total of 111 bats were
      caught in the area, belonging to three families (Emballonuridae, Molossidae and
      Phyllostomidae) and 12 species. The bat trypanosome prevalence, as evaluated
      through hemoculture, was 9% all positive cultures were cryopreserve (100% of
      isolation success). Phylogenetic trees grouped nine isolates in T. cruzi
      marinkellei branch and only one in T. dionisii branch. Studies on bat trypanosome
      diversity are important for identifying pathogenic species and for generating
      support for control measures, especially in such areas where humans inhabit the
      forest with close contact with bat species. In addition, this is the first study
      in Resex Tapajos-Arapiuns extractive reserve and further studies should be
      conducted to elucidate the role of these parasites as environmental degradation
      biomarkers.

PMID- 28746446
TI  - T lymphocytes and macrophages in the intestinal tissues of dogs infected with
      Leishmania infantum.
AB  - This study was about a semi-quantitative analysis of T lymphocytes (CD4+ and
      CD8+, FoxP3+ regulatory T cells), and macrophages in the gut wall of dogs
      naturally infected with Leishmania infantum. Thirteen dogs were divided into
      three groups: group 1 (G1, n=5), dogs with canine visceral leishmaniasis (CVL)
      and infected with L. infantum amastigotes in the intestine; group 2 (G2, n=5),
      dogs with CVL but without intestinal amastigotes; and group 3 (G3, n=3),
      uninfected dogs (control group). There was no significant difference (p >= 0.05)
      on CD4+ and Treg cell numbers among the groups, whereas the levels of CD8+ T
      cells and macrophages were significantly higher in dogs from G1 group than in G2
      and G3 (p <= 0.05), especially in intestinal segments with high parasite burden.
      Parasite burden correlated positively with levels of CD8+ T cells and macrophages
      (p <= 0.05), but was inversely correlated to levels of CD4+ T lymphocytes and
      FoxP3+ Treg cells. In conclusion, in the intestine of dogs with CVL, the increase
      of CD8+ T cells and macrophages population associated with high parasite burdens,
      but no changes of CD4+ T cells and FoxP3+ Treg cells suggest a possible
      immunoregulation by the parasite not dependent on Treg cells.

PMID- 28746447
TI  - The first assessment of the stress inducible defense of Leucaena leucocephala
      with acaricidal potential effect against Rhipicephalus (Boophilus) microplus
      (Acari: Ixodidae).
AB  - Plants respond to wounding caused by mechanical stress or herbivory by
      synthesizing defense proteins. There are no studies reporting the action of
      induced plant proteins against ticks. The aim of this study was to investigate
      the effect of mechanically wounded Leucaena leucocephala leaves against
      Rhipicephalus (Boophilus) microplus. Initially, we carried out time course
      experiments to evaluate the impact of mechanical wounding on the protein content
      and the peroxidase, catalase and protease inhibitor activities in L.
      leucocephala. We then evaluated the acaricidal activity on R. (B.) microplus from
      protein extract collected from L. leucocephala after mechanical wounding. L.
      leucocephala leaves were artificially wounded, and after 6, 12, 24 and 48h, the
      leaves were collected for protein extraction. Quantitative and qualitative
      analyses of the proteins were performed. The protein content and peroxidase and
      protease activities increased 12h after wounding, and the acaricidal activity of
      this protein extract was evaluated using engorged R. (B.) microplus females. The
      protein extract obtained after wounding reduced egg production (8.5%) compared to
      those without wounding. Furthermore, the extract reduced egg hatching by 47.7%
      and showed an overall efficacy of 56.3% at 0.1 mgP/mL of the protein. We
      demonstrated that L. leucocephala defensive proteins could be effective against
      R. (B.) microplus.

PMID- 28746448
TI  - Fatal toxoplasmosis in an immunosuppressed domestic cat from Brazil caused by
      Toxoplasma gondii clonal type I.
AB  - The objective of the study was to report on a fatal case of feline toxoplasmosis
      with coinfection with the feline leukemia virus (FeLV). A domestic cat (Felis
      silvestris catus) presented intense dyspnea and died three days later. In the
      necropsy, the lungs were firm, without collapse and with many white areas;
      moderate lymphadenomegaly and splenomegaly were also observed. The
      histopathological examination showed severe necrotic interstitial
      bronchopneumonia and mild necrotic hepatitis, associated with intralesional cysts
      and tachyzoites of Toxoplasma gondii that were positive by anti-T. gondii
      immunohistochemical (IHC) evaluation. The bone marrow showed chronic myeloid
      leukemia and the neoplastic cells were positive by anti-FeLV IHC evaluation. DNA
      extracted from lungs was positive for T. gondii by PCR targeting REP-529. T.
      gondii was characterized by PCR-RFLP and by the microsatellites technique. ToxoDB
      PCR-RFLP #10, i.e. the archetypal type I, was identified. Microsatellite analysis
      showed that the strain was a variant of type I with two atypical alleles. This
      was the first time that a T. gondii clonal type I genotype was correlated with a
      case of acute toxoplasmosis in a host in Brazil.

PMID- 28746449
TI  - Gut transcriptome analysis on females of Ornithodoros mimon (Acari: Argasidae)
      and phylogenetic inference of ticks.
AB  - Ornithodoros mimon is an argasid tick that parasitizes bats, birds and opossums
      and is also harmful to humans. Knowledge of the transcripts present in the tick
      gut helps in understanding the role of vital molecules in the digestion process
      and parasite-host relationship, while also providing information about the
      evolution of arthropod hematophagy. Thus, the present study aimed to know and
      ascertain the main molecules expressed in the gut of argasid after their blood
      meal, through analysis on the gut transcriptome of engorged females of O. mimon
      using 454-based RNA sequencing. The gut transcriptome analysis reveals several
      transcripts associated with hemoglobin digestion, such as serine, cysteine,
      aspartic proteases and metalloenzymes. The phylogenetic analysis on the
      peptidases confirmed that most of them are clustered with other tick genes. We
      recorded the presence a cathepsin O peptidase-coding transcript in ticks. The
      topology of the phylogenetic inferences, based on transcripts of inferred
      families of homologues, was similar to that of previous reports based on
      mitochondrial genome and nuclear rRNA sequences. We deposited 2,213 sequence of
      O. mimon to the public databases. Our findings may help towards better
      understanding of important argasid metabolic processes, such as digestion,
      nutrition and immunity.

PMID- 28746450
TI  - Anti-Toxoplasma gondii antibodies in beef cattle slaughtered in the metropolitan
      region of Belem, Brazilian Amazon.
AB  - The relevance of consuming raw or undercooked beef in the transmission of
      toxoplasmosis is unclear due to the high resistance of cattle to infection.
      However, this possibility needs to be considered in endemic areas, such as the
      Amazon, where the consumption of beef is frequent. The objective of this study
      was to determine the frequency of anti-Toxoplasma gondii IgG antibodies in beef
      cattle slaughtered in the metropolitan region of Belem, Para state, Brazil. Blood
      samples were collected from 500 animals of both genders in a licensed
      slaughterhouse in Belem. Anti-T. gondii IgG antibodies were detected by an
      indirect immunofluorescence assay (IFA) with a cut-off titer of 1:64. Anti-T.
      gondii antibodies were found in 203 animals (40.6%), with a titer of 64 in 112
      animals (55.2%), 128 in 68 animals (33.5%), 256 in 15 animals (7.4%), 512 in 5
      animals (2.5%), and 1,024 in 3 animals (1.4%). No significant difference was
      observed between males and females (p > 0.05). The high frequency of anti-T.
      gondii antibodies observed in beef cattle slaughtered in Belem indicates that the
      meat of these animals may be an important source of infection for humans and
      carnivorous domestic animals when inadequately cooked beef is consumed.

PMID- 28746451
TI  - Histopathological changes induced by Hysterothylacium deardorffoverstreetorum
      larvae (Nematoda: Raphidascarididae) in Priacanthus arenatus Cuvier, 1829
      (Actinopterygii).
AB  - Priacanthus arenatus is a fish that occurs in the waters of the western Atlantic
      Ocean and has few records of parasitism. This study aimed to report histological
      changes caused by the larvae of Hysterothylacium deardorffoverstreetorum. Between
      July and December, 2013, 30 samples of P. arenatus were obtained from fish
      markets in the cities of Niteroi and Rio de Janeiro, state of Rio de Janeiro,
      Brazil. Fragments of spleen, liver, stomach wall and mesentery tissues containing
      nodules and free parasites were extracted to histopathological study. Through
      histological analysis it was verified that these nodules consisted of connective
      tissue capsules, in which the parasites were located, with granulomatous
      inflammation mainly comprised of macrophages and lymphocytes. These nodules also
      consisted of a central portion of acellular amorphous material, formed by
      concentric layers, which was slightly basophilic and contained tunnels and,
      sometimes, parasite debris. The presence of tunnels in acellular amorphous
      material suggests that the larvae are initially located at the center of the
      nodules and then they migrate to the surface.

PMID- 28746452
TI  - First parasitological study of the African clawed frog (Xenopus laevis, Amphibia)
      in Chile.
AB  - Introduced species can arrive into new territories with parasites; however, these
      species are expected to face lower parasite richness than in their original
      regions. Both introduced hosts and parasites can affect native fauna. Since their
      release into the wild in Chile following laboratory use, Xenopus laevis Daudin,
      1802 has widely spread throughout central Chile. The only pathogen described on
      the host is the fungus Batrachochytrium dendrobatidis Longcore, Pessier, Nichols,
      1999; thus, this is the first parasitological study of this species in Chile. In
      10 localities in central Chile, 179 specimens of X. laevis were captured and
      examined for parasites in the gastrointestinal tube, cavities, lungs, liver, and
      skin. Only nine specimens of the genus Contracaecum Railliet, Henry, 1912 were
      found in six specimens of X. laevis from a private dam in La Patagua. It is
      likely that these parasites originated from species of native birds. This is the
      first record of Contracaecum sp. in Chilean amphibians.

PMID- 28746454
TI  - ?

PMID- 28746453
TI  - Occurrence of Paratanaisia confusa Freitas, 1951 in free-living guira cuckoo
      (Guira guira, Cuculiformes: Crotophagidae).
AB  - This report presents a description of natural infection of an adult free-living
      guira cuckoo with Paratanaisia confusa. Histological and morphological
      evaluations of renal and parasite samples were performed. The morphological
      analysis of the parasites revealed spiny tegument, characteristic of P. confusa
      helminthes. Although macroscopic alterations were absent in the kidneys, the
      histopathology revealed parasites inside the collecting ducts causing dilatation
      and destruction of the lining epithelial cells in addition to small focal
      inflammatory infiltrates in the renal parenchyma. However, as the bird was free
      living and naturally infected it was not possible to confirm if all these
      alterations were directly caused by the parasite presence or if they were related
      to causes other than the parasitism. Nonetheless, such findings indicate that
      these trematodes may have pathogenic potential in this host.

PMID- 28746455
TI  - [Isolation in comunicable diseases: a nursing concept].
AB  - The authors propose a concept about isolation in Communicable Disease Nursing,
      based on the theoretical frame of reference of the experimental - humanistic
      model.

PMID- 28746456
TI  - [Student - centered teaching: orientation to the undergraduate Pediatric Nursing
      Course].
AB  - The authors present the material currently being used in the orientation phase of
      the Pediatric Nursing I Course, which utilizes the student - centered teaching
      methodology, at the Nursing School of the Sao Paulo University.

PMID- 28746457
TI  - [Food intake of female university students].
AB  - Weighted food intake was the precedure adapted by the authors in order to find
      aut the nutritional pattern of female university students. The results revealed
      vitaminic-mineral deficiency (mainly of calcium, iron and thiamine) in relation
      to the recommended dietary allowances.

PMID- 28746458
TI  - [Considerations about the marital relationship of the pregnant woman].
AB  - The author analyses the difficultties a woman faces in her conjugal relationship
      when she is pregnant and emphasize the complexity of the variables involved in
      the origins of the problem. She also discurses the importance of the attitude of
      the personnel in dealing with these patients.

PMID- 28746459
TI  - [Study on nurse performance evaluation: used methodology and obtained results -
      Part II].
AB  - In this second part of this study the methodology, the instruments utilized for
      the data gathering and the criteria used in the discussion of the date are
      presented. Part of the discussion of the results, which, for better
      comprehension, follow a pre-established path, is also presented. The results
      concerning the itens "objectives of the performance evaluation programs" and
      "elements responsible for the performance evaluation" are discussed. This last
      item is subdivided into "profissional characterization", which is totally
      discussed in this part of the study, and "specific professional skill" which will
      be presented in the third part of this paper, The theoretical background related
      to the results is contained in the discussion presented.

PMID- 28746460
TI  - [Teaching communication therapeutic techniques in nurse-patient relationship -
      Part I].
AB  - In this paper the author presents a literature review about communication in
      nursing and psychiatric nursing. She emphasyses the use of therapeutic
      communication by nurse.

PMID- 28746461
TI  - [The use of a vibratory machine in the treatment of breast engorgement].

PMID- 28746462
TI  - [Study of the factores envolved in the hospitalization of surgical patients].

PMID- 28746463
TI  - Speech fluency profile on different tasks for individuals with Parkinson's
      disease.
AB  - Purpose: To characterize the speech fluency profile of patients with Parkinson's
      disease. Methods: Study participants were 40 individuals of both genders aged 40
      to 80 years divided into 2 groups: Research Group - RG (20 individuals with
      diagnosis of Parkinson's disease) and Control Group - CG (20 individuals with no
      communication or neurological disorders). For all of the participants, three
      speech samples involving different tasks were collected: monologue, individual
      reading, and automatic speech. Results: The RG presented a significant larger
      number of speech disruptions, both stuttering-like and typical dysfluencies, and
      higher percentage of speech discontinuity in the monologue and individual reading
      tasks compared with the CG. Both groups presented reduced number of speech
      disruptions (stuttering-like and typical dysfluencies) in the automatic speech
      task; the groups presented similar performance in this task. Regarding speech
      rate, individuals in the RG presented lower number of words and syllables per
      minute compared with those in the CG in all speech tasks. Conclusion:
      Participants of the RG presented altered parameters of speech fluency compared
      with those of the CG; however, this change in fluency cannot be considered a
      stuttering disorder.

PMID- 28746464
TI  - Elaboration of an instrument to investigate the acquisition of minimal contrast
      perception in the Brazilian sign language.
AB  - Purpose: To design an instrument to check the perception of minimal contrasts by
      through pairs of signs, which differ in one the following parameters: handshape,
      hand location, hand movement and hand orientation. Methods: An inventory of
      minimal pairs was made and some pictures were drawn by a visual artist. These
      pictures were organized into three columns, which could be equal or different
      from each other in the pair. A video file with an interpreter making two signs at
      a time was played to the individual taking the test and this was expected to
      watch the signs and point to the pictures that corresponded to them. Raters
      analyzed the pairs and decided whether or not they were accurate. They could
      modify the pairs or ask for particular pairs to be removed; they also checked if
      the pictures were clear and if they were part of the children's vocabulary.
      Results: The analysis of agreement among raters had a significant result for the
      criterion rated as 'not a minimal pair'. Thus, 13 items were removed from the
      instrument because they differed as to more than one parameter, and were
      considered either analogous or not minimal pairs. Additionally, 16 pairs were
      modified, and seven pairs which differed in orientation, were added. As a
      consequence, there was a total of 35 minimal pairs in the final version of the
      instrument. Conclusion: The purpose of designing an instrument for evaluation of
      the perception of minimal contrasts was achieved. Some adjustments were made
      during the assessment of the content of the instrument as suggested by raters.
      The final instrument was composed of 35 pairs which differ from each other in
      only one parameter.

PMID- 28746465
TI  - Orofacial characteristics of functionally independent elders.
AB  - Purpose: to understand the main orofacial characteristics of functionally
      independent elderly individuals and to investigate their association with age,
      gender, socioeconomic level, and dental status. Methods: an observational, cross
      sectional, and analytical study was carried out with a non-probabilistic sample.
      Inclusion criteria: minimum age of 60 years, individual in good health conditions
      according to a pre-established protocol published by the health care service. In
      order to collect the data, we used the validated Orofacial Myofunctional
      Evaluation with Scores for Aged Protocol. Results: The elderly individuals
      presented normal patterns in more than 60% of the appearance and mobility
      parameters. Significant alterations observed were: pronounced nasolabial sulcus;
      flaccid or arched cheeks; labial sealing with tension or absence of sealing; and
      depressed labial commissures. Alterations in mobility were few, between 20.6% and
      33.8%, with higher prevalence of alterations when raising the tongue,
      lateralizing air inflated in cheeks and jaw. There was no relationship between
      these findings and the progression of age and socioeconomic classes. Women were
      more likely to show normal appearance of lips and some alterations in lips
      mobility. The number of teeth was associated with the volume and shape of lips
      and with jaw mobility. In addition, the use of dental prosthesis was shown to be
      significantly related to the nasolabial sulcus aspect and the
      configuration/tension of cheeks. Conclusion: This study suggests normal patterns
      of oromyofacial system in most functionally independent elderly individuals. It
      supports multidisciplinary action for prevention, promotion, and treatment of the
      elderly population's oral functions.

PMID- 28746466
TI  - MicroRNA-143 inhibits cell growth by targeting ERK5 and MAP3K7 in breast cancer.
AB  - This study aimed to investigate the function and mechanism of microRNA-143 (miR
      143) in the occurrence and development of breast cancer (BC). A total of 30 BC
      tissues, 30 corresponding noncancerous tissues, and 10 normal control (NC) breast
      tissues were obtained to detect the levels of miR-143, extracellular signal
      regulated kinase 5 (ERK5) and mitogen-activated protein 3 kinase 7 (MAP3K7) using
      RT-qPCR, western blotting or immunohistochemistry. The correlation of miR-143
      with ERK5 or MAP3K7 was evaluated using Pearson correlation analysis. MCF-7 cells
      were transiently transfected with miR-143 mimic, miR-143 inhibitor, miR-143
      mimic/inhibitor + si-ERK5, si-MAP3K7 or si-cyclin D1. Then, cell growth was
      evaluated by MTT assay and the expressions of phospho-ERK5 (p-ERK5), ERK5, p
      MAP3K7, MAP3K7 and cyclin D1 were detected by western blotting. Results showed
      that, compared with noncancerous tissues or NC breast tissues, miR-143 level was
      decreased, while p-ERK5, ERK5, p-MAP3K7 and MAP3K7 expressions were increased in
      BC tissues (all P<0.01). The miR-143 level was negatively correlated with the
      mRNA level of ERK5 or MAP3K7 (r=-4.231 or r=-4.280, P<0.01). In addition, up
      regulated miR-143 significantly decreased the expressions of p-ERK5, ERK5, p
      MAP3K7, MAP3K7 and cyclin D1 (all P<0.01), as well as cell viability in MCF-7
      cells (all P<0.05) while the effect of down-regulated miR-143 was the opposite.
      In conclusion, both ERK5 and MAP3K7 may be the target genes of miR-143. Increased
      expression of miR-143 can inhibit cell growth, which may be associated with ERK5
      and MAP3K7 expressions in BC.

PMID- 28746467
TI  - Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and
      modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice.
AB  - Asthma is a chronic allergic disease characterized by airway inflammation, airway
      hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved
      in the pathogenesis of asthma, mediating airway inflammatory reactions by
      secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling
      pathways are associated with T cell signaling, proliferation, and
      differentiation, and are important in the progression of asthma. Thus, compounds
      that can modulate T cell proliferation and function may be of clinical value.
      Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in
      experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with
      ovalbumin (OVA). Separate groups of mice (n=18/group) were administered
      tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used
      as a positive control. Tangeretin treatment reduced inflammatory cell
      infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal
      histology of lung tissues. OVA-specific IgE levels in serum and BALF were
      reduced. AHR, as determined by airway resistance and lung compliance, was
      normalized. Flow cytometry analyses revealed a reduced Th17 cell population.
      Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-gamma
      levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and
      its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support
      the possible use of tangeretin for treating allergic asthma.

PMID- 28746468
TI  - Ischemic preconditioning vs adenosine vs prostaglandin E1 for protection against
      liver ischemia/reperfusion injury.
AB  - Ischemia/reperfusion injury is still a major cause of morbidity and mortality
      during liver surgery and transplantation. A variety of surgical and
      pharmacological therapeutic strategies have been investigated to minimize the
      effects of ischemia/reperfusion. The aim of our study was to analyze and compare
      preventive influences of ischemic preconditioning, adenosine and prostaglandin E1
      in the experimental model of hepatic ischemia/reperfusion injury. Adult
      chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver
      ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min
      period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits
      subjected to pre-treatment with intraportal injection of adenosine followed by 45
      min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal
      injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control
      group of 10 rabbits subjected to 45 min of inflow liver ischemia without any
      preconditioning. On the second postoperative day, blood samples were obtained and
      biochemical parameters of liver function were measured and compared. Liver tissue
      samples were also obtained and histopathological changes were compared. Based on
      biochemical and histopathological parameters, it was demonstrated that ischemic
      preconditioning provided the best protection against hepatic ischemia/reperfusion
      injury. This was probably due to a wider range of mechanisms of action of this
      method oriented to reduce oxidative stress and inflammation, and restore liver
      microcirculation and hepatocyte energy compared to the examined pharmacological
      strategies.

PMID- 28746469
TI  - Interleukin-27 augments the inhibitory effects of sorafenib on bladder cancer
      cells.
AB  - Both sorafenib and interleukin-27 (IL-27) are antineoplastic drugs. This study
      aimed to investigate the synergistic effect of these two drugs on bladder cancer
      cells. HTB-9 and T24 cells were stimulated with IL-27 (50 ng/mL), sorafenib (2
      MUM) or the synergistic action of these two drugs. The cells without treatment
      acted as control. Cell proliferation, apoptosis and invasion were measured by
      bromodeoxyuridine assay, flow cytometry and modified Boyden chamber,
      respectively. Simultaneously, both modified Boyden chamber and scratch assay were
      used to assess cell migration. Finally, the phosphorylation levels of key kinases
      in the Akt/mechanistic target of rapamycin (mTOR)/mitogen-activated protein
      kinase (MAPK) pathway, and expression levels of matrix metalloproteinase (MMP)-2
      and MMP-9 were detected by western blot analysis. Stimulation with IL-27 or
      sorafenib repressed proliferation, migration and invasion but promoted apoptosis,
      and the effects were all enhanced by the combination of these two drugs in HTB-9
      cells. The effect of the combined treatment on bladder cancer cells was verified
      in T24 cells. Additionally, the phosphorylation levels of AKT, mTOR and MAPK as
      well as the expression levels of MMP-2 and MMP-9 were all decreased by a single
      treatment of IL-27 or sorafenib, and further decreased by the combined treatment
      of these two drugs. The combination of IL-27 and sorafenib inhibited
      proliferation, migration and invasion and promoted apoptosis of bladder cancer
      cells compared with mono-drug treatment. Additionally, the AKT/mTOR/MAPK pathway
      might be implicated in the functional effects by down-regulations of MMP-2 and
      MMP-9.

PMID- 28746470
TI  - Relationship between ventilation heterogeneity and exercise intolerance in adults
      with sickle cell anemia.
AB  - Sickle cell anemia (SCA) causes dysfunction of multiple organs, with pulmonary
      involvement as a major cause of mortality. Recently, there has been growing
      interest in the nitrogen single-breath washout (N2SBW) test, which is able to
      detect ventilation heterogeneity and small airway disease when the results of
      other pulmonary function tests (PFTs) are still normal. Thus, the objectives of
      the present study were to assess the heterogeneity in the ventilation
      distribution in adults with SCA and to determine the association between the
      ventilation distribution and the clinical, cardiovascular, and radiological
      findings. This cross-sectional study included 38 adults with SCA who underwent
      PFTs, echocardiography, computed tomography (CT), and 6-min walk test. To
      evaluate the ventilation heterogeneity, the patients were categorized according
      to the phase III slope of the N2SBW (SIIIN2). Compared with adults with lower
      SIIIN2 values, adults with higher SIIIN2 values showed lower hemoglobin levels
      (P=0.048), a history of acute chest syndrome (P=0.001), an elevated tricuspid
      regurgitation velocity (P=0.039), predominance of a reticular pattern in the CT
      (P=0.002), a shorter 6-min walking distance (6MWD) (P=0.002), and lower
      peripheral oxygen saturation (SpO2) after exercise (P=0.03). SIIIN2 values
      correlated significantly with hemoglobin (rs=-0.344; P=0.034), forced vital
      capacity (rs=-0.671; P<0.0001), diffusing capacity for carbon monoxide (rs=
      0.376; P=0.019), 6MWD (rs=-0.554; P=0.0003), and SpO2 after exercise (P=0.040).
      Heterogeneity in the ventilation distribution is one of the most common pulmonary
      dysfunctions in adults with SCA. Moreover, relationships exist between
      ventilation heterogeneity, worsening of pulmonary structural damage, and reduced
      tolerance for exercise.

PMID- 28746471
TI  - Impact of extracellular alkalinization on the survival of human CD24-/CD44+
      breast cancer stem cells associated with cellular metabolic shifts.
AB  - Cancer stem cells reside in a distinct region within the tumor microenvironment
      that it is believed to play a fundamental role in regulating stemness,
      proliferation, survival, and metabolism of cancer cells. This study aimed to
      analyze the effect of extracellular alkalinization on metabolism and survival of
      human CD24-/CD44+ breast cancer stem cells (BCSCs). BCSCs were cultured in
      alkalinized DMEM-F12 and incubated at 37 degrees C, 5% CO2, and 20% O2 for 30
      min, 6, 24, and 48 h. After each incubation period, we analyzed the modulation of
      various mRNA expressions related to pH and cellular metabolic regulation using
      the qRT-PCR. Metabolic state was measured using colorimetric and fluorometric
      assays. To examine cell proliferation and apoptosis, we used trypan blue and
      annexin V/propidium iodide assay, respectively. This study demonstrated that
      alkalinization could stimulate extracellular carbonic anhydrase (CAe) activity,
      as well as CA9 and HIF1alpha expression. Under alkaline pH and HIF1alpha
      regulation, glucose consumption, extracellular lactate production, and LDH
      activity of BCSCs were upregulated while O2 consumption was downregulated. These
      metabolic shifts seemed to promote apoptosis and suppress the proliferation of
      BCSCs. To conclude, modulation of the extracellular environment through
      alkalinization could change the metabolic states of BCSCs, which in turn affect
      the cell survival.

PMID- 28746472
TI  - ?

PMID- 28746473
TI  - [Nursing personnel budgeting: a nurse's function].
AB  - The authors analyse the problem faced by the Nursing Service of a hospital when
      budgeting nursing personnel for patient care. They refer that the hospitals, at
      first, may use prestablished calculation in the literature, but they emphasize
      that later on, the estimatis must be corrected by their observation of the daily
      number of hours of care required by the patient in that particular situation and
      other local factors which interfere with nursing assistance.

PMID- 28746474
TI  - [Evaluating the iron nutritional status of female university students].
AB  - A study to evaluate the iron nutritional status was carried out envolving 47
      female university students, whose diets contained the average of 72% of the
      recommented dietary allowances of iron. The results show that, in spite of the
      low consumption of iron, the concentration of hemoglobin and the value of
      hematocrit was within the border line of normality. The possibility of the
      organic iron stores being minimal or absent is discussed.

PMID- 28746475
TI  - [Nursing physical problems of patients in the intensive care unit].
AB  - The nursing problems of patients in intensive care unit about their physical area
      were studied. The parameters to be investigate systematically at physical
      examination were determined. The statistical study revealed nursing problems
      qualitatively significatives in paremeters investigated.

PMID- 28746476
TI  - [Coronary patient and the environment of intensive care unit: an approach of
      invasive procedures].
AB  - This is a study about the influence of the quantity of invasive procedures to
      which the patient of an intensive care unit is submitted, and its relation to his
      perception of his environment. A hundreed patients with medical diagnosis of
      acute heart insufficiency, all of the same unit, have been interviewed. They were
      divided into 2 groups: Group A (submitted to more invasive procedures) and group
      B (submitted to a lesser number of invasive procedures). The statistical analysis
      showed that there was no difference between Group A and Group B in the quantity
      and nature of problems. The majority of the patients of the two groups felt
      mostly the problem of being inside a hospital, away from home. Only a minority
      described problems referring to sounds and images of their environment.

PMID- 28746477
TI  - [Risks and self-protection measures in the handling of anti-neoplasic drugs].
AB  - The authors, undergraduate nursing students, report their observation, in two
      hospitals, of anti-neoplasic drugs handling by nursing personel. Their objective
      was to verify which self-protect ion measures were adopted by them. They also
      describe how such handling should be done.

PMID- 28746478
TI  - [Specialization course in intensive care nursing - part. I: student's prolife].
AB  - This is Part I of a two part papers. After completing five specialization courses
      in intensive care nursing, the authors report their experience in this Part and
      they describe the type of students all graduate nurses, who enrolled in such
      courses.

PMID- 28746479
TI  - [Nursing care to children with burn injuries].
AB  - The author outline the most common causes of burn injuries in children, the
      classification of burns according to the seriousness of the wounds and the
      physical and psychological care of such patients. She also mentions the attention
      to be given to burned children's parents.

PMID- 28746480
TI  - [Nurse patient therapeutic relationship].
AB  - The authors, a nursing student and her instructor, report their experience, in a
      psychiatric hospital, with a patient whose behaviour was characterized by
      suspiciouness and tell how the student succeeded in helping him. They pount out
      the nurse -patient therapeutic relationship as the basis on which psychiatric
      nursing is founded.

PMID- 28746481
TI  - [The teaching of the nursing process to undergraduate students].
AB  - The authors, instructors of Fundamentals of Nursing, describe two experiments in
      teaching nursing process, for which two different types of field of practice were
      used: the nursing personnel of the first hospital did not employ the nursing
      process in the care of their patients, but on the second hospital the utilization
      of this process had been adopted. Two outstanding expected results were obtained:
      1. The group of students, who practised in the first hospital did not believe the
      utilization of the nursing process would be possible in professional practices;
      but the groups who had seen such process being used showed a totally different
      attitude and agreed about the convenience of the adaption of the nursing process
      by the hospitals; 2. the students who are taking Fundamentals of Nursing are not
      get prepared to identify nursing problems and to suggest solution, owing to their
      lack of knowledge of pathology. The authors recommend the teaching of the nursing
      process gradually, througout the undergraduate course, in order to secure more
      effective results.

PMID- 28746482
TI  - [THE NURSES' EMOTIONAL REACTIONS IN THEIR PROFESSIONAL DUTIES].

PMID- 28746483
TI  - Stability of orthodontic treatment and dental extractions.

PMID- 28746484
TI  - Obesity and orthodontic treatment: is there any direct relationship?
AB  - Obesity is a wide-spread condition directly or indirectly connected with an
      increase in the prevalence of a variety of human diseases. It affects over 50% of
      the western overall population. In 2017, a thorough analysis of 204 studies on
      obesity and cancer revealed that the condition increases the risk of the
      following types of cancer: stomach, colon, rectal, bile duct, pancreatic,
      esophagus, breast, endometrial, ovarian, kidney and multiple myeloma. The first
      study aiming at establishing a connection between obesity and the rate of induced
      orthodontic tooth movement was conducted by Saloom et al; however, it could not
      effectively nor significantly reveal any direct influence or effect. Despite
      being identified during the first week, differences could not be explained and
      treatment time remained unchanged. In spite of lack of studies in the literature
      on the connection between obesity and the rate of induced tooth movement, in
      clinical practice, courses or specialized training, we should not have protocols
      changed nor adopt any measures or expect significant differences between normal
      weight and obese individuals. It should be emphasized that unsuccessful cases or
      cases of root resorption associated with treatment should not be assigned to
      obesity, since scientific data is insufficient to do so.

PMID- 28746485
TI  - An interview with Steven J. Lindauer.
AB  - There are so many compliments to Dr. Steven Lindauer that is hard for one to
      figure where to start from... Well, travelling backwards in time, all the way to
      the year 2000, I went to Virginia to study English at Virginia Commonwealth
      University (VCU), in Richmond, Virginia, USA. During my daily walks to the
      English school, I used to pass by the School of Dentistry, where the Department
      of Orthodontics was. That was the place where my very first "contact" with the
      VCU happened. In 2015, 15 years later, I had the pleasure to go back to the VCU
      and spend two days with Dr. Steven Lindauer. I have to confess that I was anxious
      and nervous to get to know not only the Chair of the Department, but also the
      Editor-in-chief of "The Angle Orthodontist". Since the very first moment I could
      experience how incredibly positive and pro-active the environment within the
      Department was. Staff members, Residents and Faculty members used to work very
      gladly and in perfect synergy. After a quick chat with the residents, I heard
      from them: "Dr. Lindauer is an unprecedented human being! Besides a brilliant
      Professor, Researcher and Administrator, he is like a father to all of us!"
      Besides this touching testimony, I also heard flattering compliments from
      workmates to the great friend, leader and partner Dr. Lindauer was. Here goes
      some food for thought, though. Unfortunately, the leader is often compelled to
      resort to unpopular measures in order to enforce compliance. Dr Lindauer is the
      living proof that a boss, a leader, can be a light, humble, friendly and highly
      charismatic human being. In 2016, I was given a second chance to enjoy Dr.
      Lindauer's company when he visited Brazil as a guest lecturer in Salvador, at the
      Federal University of Bahia and the Brazilian Association of Orthodontics (Bahia
      Chapter). I noticed, once again, that besides an excellent lecturer and careful
      clinician, he mastered orthodontic mechanics very proficiently. And needless to
      say at length about his brilliance ahead of "The Angle Orthodontist"... It didn't
      take me long to realize that his virtues by far exceeded the boundaries of the
      professional domain. Despite his utterly busy schedule, he is still able to
      dedicate time to his parents, taking them to trips around the world.
      Interestingly, at every international trip, he always remembers his puppies
      (Memphis, Baxter and Kingston - in memoriam), taking sightseeing pictures to
      immediately Photoshop them into. Having done the well deserved introductions to
      our distinguished interviewee, I would like to offer righteous acknowledgements
      to the colleagues Jorge Faber, David Turpin, Bhavna Shroff and David Normando,
      for having accepted the invitation to take part in this interview. I also would
      like to offer my heartfelt thanks to Dental Press for having entrusted me with
      the honor to conduct this project. I wish all readers as delightful and rich of
      an experience when going through this interview as it's been the scientific path
      that brought us all here in the first place. No doubts, you stand in face of a
      life dedicated to Orthodontics. (Andre Wilson Machado, interview coordinator).

PMID- 28746486
TI  - Normative need for orthodontic treatment and perception of the need for such
      treatment among Brazilian adolescents.
AB  - Objective:: The aim of the present study was to evaluate the normative need for
      orthodontic treatment and the perception of such need among students aged 11-14
      years. Methods:: A cross-sectional study was conducted with a sample of 346
      students, randomly selected from public and private schools. The Dental Aesthetic
      Index (DAI) was used to evaluate the normative need for orthodontic treatment
      (NNOT). The perceived need for treatment among students was assessed by a
      previously validated questionnaire. Data was analyzed by Pearson's Chi-squared
      test (alpha = 5%). Results:: The prevalence of malocclusion and NNOT was 65.6%.
      Of the sample, 73.7% felt they needed treatment, 66.2% wanted orthodontic
      treatment and 62.7% were satisfied with their dental aesthetics. A statistically
      significant association was observed between NNOT and the perception of the need
      for treatment among the students (p < 0.001). Conclusion:: The present study
      demonstrated a high prevalence of malocclusion, which was reflected in the high
      normative need for orthodontic treatment. The opinion of patients regarding their
      expectations of orthodontic treatment should be valued. The students perceived a
      need for orthodontic treatment.

PMID- 28746487
TI  - Fracture strength of orthodontic mini-implants.
AB  - Objective:: This study aimed at evaluating the design and dimensions of five
      different brands of orthodontic mini-implants, as well as their influence on
      torsional fracture strength. Methods: : Fifty mini-implants were divided into
      five groups corresponding to different manufactures (DEN, RMO, CON, NEO, SIN).
      Twenty-five mini-implants were subjected to fracture test by torsion in the neck
      and the tip, through arbors attached to a Universal Mechanical Testing Machine.
      The other 25 mini-implants were subjected to insertion torque test into blocks of
      pork ribs using a torquimeter and contra-angle handpiece mounted in a surgical
      motor. The shape of the active tip of the mini-implants was evaluated under
      microscopy. The non-parametric Friedman test and Snedecor's F in analysis of
      variance (ANOVA) were used to evaluate the differences between groups. Results::
      The fracture torque of the neck ranged from 23.45 N.cm (DEN) to 34.82 N.cm (SIN),
      and of the tip ranged from 9.35 N.cm (CON) to 24.36 N.cm (NEO). Insertion torque
      values ranged from 6.6 N.cm (RMO) to 10.2 N.cm (NEO). The characteristics that
      most influenced the results were outer diameter, inner diameter, the ratio
      between internal and external diameters, and the existence of milling in the
      apical region of the mini-implant. Conclusions: : The fracture torques were
      different for both the neck and the tip of the five types evaluated. NEO and SIN
      mini-implants showed the highest resistance to fracture of the neck and tip. The
      fracture torques of both tip and neck were higher than the torque required to
      insert mini-implants.

PMID- 28746488
TI  - Mandibular dental arch short and long-term spontaneous dentoalveolar changes
      after slow or rapid maxillary expansion: a systematic review.
AB  - Objective:: The aim of this systematic review was to analyze the short and long
      term spontaneous dentoalveolar changes of the mandibular dental arch after slow
      (SME) or rapid (RME) maxillary expansion in the mixed and early permanent
      dentitions. Methods:: An electronic search was performed in the following
      databases: PubMed/Medline, Cochrane Library, Scopus, Embase and Web of Science.
      Eligibility criteria for article selection included randomized controlled trials
      and prospective studies written in English, with no restriction of year of
      publication, involving patients who underwent SME or RME during the mixed or
      early permanent dentitions. A double-blind search of articles was performed by
      two reviewers. Initially, the title and the abstract of the studies were read,
      and their references were also hand-searched for possible missing studies. A
      methodological quality scoring scale was used to analyze the selected articles.
      Results:: The search retrieved 373 articles, but only 6 were selected for review
      after application of the eligibility and exclusion criteria. Non-clinically
      significant spontaneous dentoalveolar changes of approximately 1mm were found in
      the mandibular dental arch in the short and long-term, after slow or rapid
      maxillary expansions. Furthermore, no significant differences were found between
      treated and control groups. Conclusions: : There is enough evidence to conclude
      that negligible short and long-term spontaneous dentoalveolar changes tend to
      occur in the mandibular dental arch after SME or RME in the mixed and early
      permanent dentitions. More randomized studies with appropriate control group are
      required to better evaluate this issue.

PMID- 28746489
TI  - Three-dimensional evaluation of mandibular anterior dental crowding in digital
      dental casts.
AB  - Introduction:: Digital dental models provide a more accurate and comprehensive
      assessment of orthodontic cases. Although this technique is quite promising,
      there are few three-dimensional measurements methods described in the literature.
      Objective:: The aim of this study was to propose a method for assessing the
      degree of mandibular anterior dental crowding in the three planes of space, using
      digital dental models. Methods: : Thirty dental casts were selected and scanned
      by Maestro 3D Dental Scanner and imported by Geomagic Qualify 2013 software. The
      degree of crowding was calculated by two examiners, based on the Little's
      Irregularity Index, by means of the definition of axial, coronal and sagittal
      planes for each model. Intraexaminer analysis was performed with Dahlberg's
      Formula (DF) and Intraclass Correlation Coefficients (ICC), and interexaminer
      analysis was performed with ICC and paired t-test. Results: : The ICC showed an
      excellent agreement (p < 0.05) for all measurements, except for the intraexaminer
      and interexaminer in the Z-axis, in which it was found a moderate agreement. The
      DF showed a satisfactory accuracy with all measurements showing less than 1 mm
      difference. The paired t-test showed statistical difference between the examiners
      in two measurements, although it was clinical irrelevant. Conclusion: : When
      comparing the three planes of space, the Z-axis showed the greatest variation in
      landmarks placement; however, overall, the present method seems precise and
      reproducible.

PMID- 28746490
TI  - Is the main goal of mastication achieved after orthodontic treatment? A
      prospective longitudinal study.
AB  - Objective:: To investigate the masticatory and swallowing performances in
      patients with malocclusions before and after orthodontic treatment, comparing
      them to an age- and gender-matched control group with normal occlusion. Methods:
      : Twenty-three patients with malocclusions requiring orthodontic treatment were
      included in this prospective study. One month after appliance removal, seventeen
      patients completed a follow-up examination and the data were compared with those
      of a control group with thirty subjects with normal occlusion. Masticatory
      performance was determined by the median particle size for the Optocal Plus(r)
      test food after 15 chewing strokes, and three variables related to swallowing
      were assessed: a) time and b) number of strokes needed to prepare the test-food
      for swallowing, and c) median particle size of the crushed particles at the
      moment of swallowing. Results: : At the baseline examination, the malocclusion
      group had a significantly lower masticatory performance and did not reach the
      particle size reduction at the moment of swallowing, when compared with the
      control group. After treatment, the masticatory performance significantly
      improved in the malocclusion group and the particle size reduction at swallowing
      reached the same level as in the control group. Conclusions: : The present
      results showed that the correction of malocclusions with fixed appliances can
      objectively provide positive effects in both mastication and deglutition
      processes, reinforcing that besides aesthetic reasons, there are also functional
      indications for orthodontic treatment.

PMID- 28746491
TI  - Impact of rapid maxillary expansion on nasomaxillary complex volume in mouth
      breathers.
AB  - Objective:: To assess the volumetric changes that occur in the nasomaxillary
      complex of mouth-breathing patients with transverse maxillary deficiency
      subjected to rapid maxillary expansion (RME). Methods:: This was a controlled,
      prospective intervention study involving 38 mouth-breathing patients presenting
      with transverse maxillary deficiency, regardless of malocclusion type or race.
      Twenty-three of them comprised the experimental group, which was composed of 11
      (47.8%) boys, and 12 (52.2%) girls, with a mean age of 9.6 years, ranging from
      6.4 to 14.2 years and standard deviation of 2.3 years; and 15 of them comprised
      the control group, composed of 9 (60%) boys and 6 (40%) girls with an mean age of
      10.5 years, ranging from 8.0 to 13.6 years, and standard deviation of 1.9 years.
      All patients were scanned (CT) according to a standard protocol: Initial CT (T1),
      and CT three months thereafter (T2), and the patients in the experimental group
      were treated with RME using a Hyrax expander for the correction of maxillary
      deficiency during the T1-T2 interval. The CT scans were manipulated using
      Dolphin(r) Imaging version 11.7 software for total and partial volumetric
      assessment of the nasomaxillary complex. Results:: The results revealed that in
      the experimental group there was a significant increase in the size of the
      structures of interest compared to the control group, both in general aspect and
      in specific regions. Conclusions:: Rapid maxillary expansion (RME) provided a
      significant expansion in all the structures of the nasomaxillary complex (nasal
      cavity, oropharynx, right and left maxillary sinuses).

PMID- 28746492
TI  - Relationship between dental calcification and skeletal maturation in a Peruvian
      sample.
AB  - Objective:: the objective of the study was to determine the relationship between
      dental calcification stages and skeletal maturation in a Peruvian sample.
      Methods: : panoramic, cephalometric and carpal radiographs of 78 patients (34
      girls and 44 boys) between 7 and 17 years old (9.90 +/- 2.5 years) were
      evaluated. Stages of tooth calcification of the mandibular canine, first
      premolar, second premolar, and second molar and the skeletal maturation with a
      hand-wrist and a cervical vertebrae method were assessed. The relationships
      between the stages were assessed using Spearman's correlation coefficient.
      Additionally, the associations of mandibular and pubertal growth peak stages with
      tooth calcification were evaluated by Fisher's exact test. Results:: all teeth
      showed positive and statistically significant correlations, the highest
      correlation was between the mandibular second molar calcification stages with
      hand-wrist maturation stages (r = 0.758, p < 0.001) and with vertebrae cervical
      maturation stages (r = 0.605, p < 0.001). The pubertal growth spurt was found in
      the G stage of calcification of the second mandibular molar, and the mandibular
      growth peak was found in the F stage of calcification of the second molar.
      Conclusion: : there was a positive relationship between dental calcification
      stages and skeletal maturation stages by hand-wrist and cervical vertebrae
      methods in the sample studied. Dental calcification stages of the second
      mandibular molar showed the highest positive correlation with the hand-wrist and
      cervical vertebrae stages.

PMID- 28746493
TI  - Miniscrew-assisted rapid palatal expansion for managing arch perimeter in an
      adult patient.
AB  - Introduction:: Etiology of dental crowding may be related to arch constriction in
      diverse dimensions, and an appropriate manipulation of arch perimeter by
      intervening in basal bone discrepancies cases, may be a key for crowding relief,
      especially when incisors movement is limited due to underlying pathology,
      periodontal issues or restrictions related to soft tissue profile. Objectives: :
      This case report illustrates a 24-year old woman, with maxillary transverse
      deficiency, upper and lower arches crowding, Class II, division 1, subdivision
      right relationship, previous upper incisors traumatic episode and straight
      profile. A non-surgical and non-extraction treatment approach was feasible due to
      the miniscrew-assisted rapid palatal expansion technique (MARPE). Methods: : The
      MARPE appliance consisted of a conventional Hyrax expander supported by four
      orthodontic miniscrews. A slow expansion protocol was adopted, with an overall of
      40 days of activation and a 3-month retention period. Intrusive traction
      miniscrew-anchored mechanics were used for correcting the Class II subdivision
      relationship, managing lower arch perimeter and midline deviation before
      including the upper central incisors. Results: : Post-treatment records show an
      intermolar width increase of 5 mm, bilateral Class I molar and canine
      relationships, upper and lower crowding resolution, coincident dental midlines
      and proper intercuspation. Conclusions: : The MARPE is an effective treatment
      approach for managing arch-perimeter deficiencies related to maxillary transverse
      discrepancies in adult patients.

PMID- 28746494
TI  - Angle Class III malocclusion with anteroposterior and vertical discrepancy in the
      final stage of growth.
AB  - Angle Class III malocclusion is characterized by an anteroposterior dental
      discrepancy with or without anteroposterior and vertical skeletal changes.
      Patients usually seek orthodontic treatment because facial appearance is
      compromised in most cases. The present study describes the clinical case of a 12
      year and 6-month-old girl in her final stage of pubertal growth presenting Class
      III malocclusion with anteroposterior and vertical discrepancies. Initial
      treatment consisted of maxillary expansion using a Hass expander followed by the
      use of a Petit facemask for a minimum of 16 hours a day. During corrective
      treatment, Class III elastics were used to complement protraction. At the end of
      the treatment, skeletal discrepancy had improved, and the ANB angle increased
      from 0 to 2o. Angle Class III malocclusion, anterior crossbite and open bite were
      corrected. This case was presented to the Committee of the Brazilian Board of
      Orthodontics and Facial Orthopedics (BBO) as part of the requisites to become a
      BBO Diplomate.

PMID- 28746496
TI  - Hospitalized school children: proposition of a data collection instrument in
      light of Horta's theory.
AB  - Objetivo: To build a data collection tool for hospitalized schoolchildren in
      light of the Theory of Basic Human Needs. Method: Methodological research
      developed in a a Teaching Hospital in Joao Pessoa, with the participation of
      eight teachers and assistant nurses, from July 2014 to March 2015. Statistical
      analysis was used to validate the empirical indicators. Resultados: The
      indicators were identified from the instrument analysis validated for children,
      considering the International Nursing Minimum Data Set, which resulted in version
      1 of the instrument with 301 indicators. The instrument validation resulted in
      288 indicators, which were later revalidated and formatted once the instrument's
      final version was reached. Conclusion: The instrument has contributed to data
      collection in teaching hospitals and has guided the other phases of the nursing
      process, considering the specific needs of these children, collaborating with the
      nursing care, education and research.

PMID- 28746495
TI  - Epithelial rests of Malassez: from latent cells to active participation in
      orthodontic movement.
AB  - Introduction:: The epithelial rests of Malassez (ERM) represent a group of cells
      in the periodontal ligament classically consisting of latent or quiescent
      structures associated with pathological processes. However, recent evidence shows
      that these structures cannot be considered only as cellular debris. The ERM is a
      major tissue structure, with functions in maintaining the homeostasis of
      periodontal tissue, including the maintenance of orthodontic movement.
      Objective:: The present literature review aims at presenting the potential
      functions of ERM, with emphasis on orthodontic movement and the functional
      structure of the periodontium. Conclusion:: ERM cells have a functional activity
      in modulation of orthodontic movement, trough their potential for
      differentiation, maintenance functions and the capacity of repairing
      periodontium.

PMID- 28746497
TI  - Revealing an HIV diagnosis for children and adolescents: subsidy for the practice
      of care.
AB  - Objective: To collectively build a guide for following-up on HIV diagnosis
      disclosure to children and adolescents in a specialized service. Method:
      Convergent-care research approach with observation triangulation, interview and
      groups, conducted from May to June 2015 with seven health professionals in a
      pediatric outpatient clinic for infectious diseases. Thematic content analysis
      was developed. Results: The discussion of understanding the disclosure, its
      triggers, actors involved, used strategies, and limits and possibilities listed
      by the professionals subsidized the construction of a guide to be applied in the
      stages: analyzing children's questions and curiosities; evaluating their
      cognitive ability; discussing the reasons to reveal; listing the professionals
      involved on follow-up process; including family; developing strategies for
      disclosure. Conclusion: This guide may mediate changes in care practice to ensure
      the child's rights and to make the professionals co-accountable.

PMID- 28746498
TI  - Factors associated with the interruption of exclusive breastfeeding in infants up
      to 30 days old.
AB  - Objective: To identify factors associated with the interruption of exclusive
      breastfeeding (EBF) in infants up to 30 days old. Method: A cross-sectional study
      conducted at a university hospital in southern Brazil, from December 2014 to
      September 2015, with 341 infants up to 30 days old and their mothers. A semi
      structured questionnaire was applied consisting of variables related to
      sociodemographic characteristics, obstetric history of the mother, companion's
      education, and data of the infant and of breastfeeding. Collected data were
      subjected to bivariate and multivariate analysis with the estimation of
      Prevalence Ratios (PR). Results: The prevalence of EBF was 79.5%. The factors
      associated with the interruption of EBF were babies >= 21 days, who received
      formula supplementation at the hospital, women with difficulties breastfeeding
      after hospital discharge, and non-white. Conclusion: the factors associated with
      EBF interruption can help health workers create actions for mothers with
      difficulties and prevent interruption of EBF.

PMID- 28746499
TI  - Strengths and weaknesses of the nursing certificate program at the Instituto
      Federal de Santa Catarina (Federal Institute of Santa Catarina).
AB  - Objective: To analyze the strengths and weaknesses found in the implementation
      process of the Nursing Certificate Program at the Instituto Federal de Santa
      Catarina (Federal Institute of Santa Catarina), in the 2000s. Method: Socio
      historical research with a qualitative approach. Oral history as a method source
      for data collection between June/September 2015, with thematic analysis. Seven
      professionals participated in the study, resulting in three categories:
      Recognition of the Nursing Certificate Program in the community and work market;
      Weaknesses faced by the course; Strengths during the implementation of the
      course. Results: The course was accepted by the labor market, resulting in an
      increased demand. As weaknesses: insufficient materials and structure, few
      teachers, course is offered every two years and no understanding of the stages by
      the institution. As strengths: commitment of teachers, management support and
      incentives to perform research. Final considerations: Despite the weaknesses, the
      strengths contributed to the implementation of the Nursing Certificate Program
      overcoming challenges, ensuring improvement in vocational training.

PMID- 28746500
TI  - Domestic violence against children and adolescents: social support network
      perspectives.
AB  - Objective: To identify and analyze the social support network of families
      involved in violence against children and adolescents, from the perspective of
      health professionals and families in a municipality of the state of Sao Paulo,
      Brazil. Methods: This was a qualitative strategic social study, anchored in the
      paradigm of complexity. Data were collected from 41 health professionals and 15
      families using institutional or personal network maps, and semi-structured
      interviews. Analysis was conducted by organizing the data, constructing
      theoretical frameworks, and categorizing resulting information. Results: The
      category "weaving the network" was unveiled, with family experiences and
      professionals focused on a logic of fragmentation of care. Final considerations:
      The creation and implementation of public policy are urgently needed to address
      the needs of this population, by empowering families and communities and
      developing research that respects the multidimensional nature of the phenomenon.

PMID- 28746501
TI  - Social ruptures and the everyday life of homeless people: an ethnographic study.
AB  - Objective: To discover the generators of disruptions in social support networks
      and identify the everyday life and projects of life of homeless people. Method:
      Ethnographic study conducted between 2012 and 2013 in Ribeirao Preto -SP, Brazil.
      The participants were fifteen homeless people. Data were collected through video
      recorded interviews addressing histories of life and a field diary. Data analysis
      was based on Habermas' Theory of Communicative Action. Results: Results revealed
      that the participants' families have faced inequalities for many generations and
      that everyday life is marked by violence and death, poverty and exclusion,
      disrupted social networks, loneliness, alcohol and drug consumption, and other
      socially determined diseases. Conclusion: The situation of living on the streets
      stems from several factors present in the organization of the Brazilian society
      and social determinants condition the life and health of homeless people.

PMID- 28746502
TI  - [First Interamerican Symposium on Qualitative Research in Nursing].

PMID- 28746503
TI  - [Nursing care to patient with diseases of the blood].
AB  - The present paper focuses genera! considerations about the care of the patient
      with diseases of the blood. The autors assess the patient's usual problems and
      present some purposes to solve them.

PMID- 28746504
TI  - [Nursing care given to private pacients by nursing students' - report of an
      experience].
AB  - In this article the author describes her experience with Junior Student Nurses -
      5th semesters - discipline of Medical-Surgical Nursing, at the School of Nursing
      and Obstetrics, Federal University of Minas Gerais. The experiment was to
      introduce the students in the care of private patients in a Surgical Unit. The
      study relates the student's opinions about the importance of the learning
      experience with these different segment of the clientele.

PMID- 28746505
TI  - [Public health nursing in leprosy control: analysis of work done achieved].
AB  - In this paper, the author presents a comparative study of the work done by the
      nursing personnel in Health Center I of the Regional Health Department of
      Ribeirao Preto, State Health Bureau of the State of Sao Paulo, in compliance with
      the recommentaiions set forth by the Sub-program for the Controle of Leprosy. It
      should be stressed that the nurses' work was of a mainly administrative and
      advisory nature.

PMID- 28746506
TI  - [Nursing publication - a survey of priorities].
AB  - The Special Comission on Text-Book of the Nursing Brasilian Association (ABEn)
      developed a survey to stablish priorities for nursing publication in Brazil. A
      questionnaire was sent to three teachers of every brazilian school of nursing and
      the following subjects were emphasized: areas that needed coverage; difficulties
      encountered by professors in the edition of nursing texts; and their preference
      for available vehicles. 47,6% of the schools returned the questionnaires, but
      only 39,5% of the professors answered. A general lack of pertinent literature was
      recognized, but Psychiatric Nursing and Public Health were areas most frequently
      indicated. Professors expressed a general lack of both, the available time and
      financial resources, that were recognized as major difficulties for an effective
      dissemination of professional information.

PMID- 28746507
TI  - [The personalistic instruction system: an expedient for education in nursing].
AB  - The author emphasizes the characteristics and application of the Keller Method, a
      individualized instruction method. Highlights the feasiblilift for Nursing usage,
      either in formal or continued education.

PMID- 28746508
TI  - [The inclusion of Medical Surgical Nursing in the health system].
AB  - The authors analyse the conception of medical surgical based in a social and
      assistencial view besides to discuss the human and institutional recourses in the
      health system.

PMID- 28746509
TI  - [Nursing consultation of the hypertensive patient: analysis of a current
      instrument and development of a new model].
AB  - This is a preliminary study on nursing consultation for hypertensive patients and
      analysis of the instrument used in a cardiology hospital. The development of an
      adequate instrument for this kind of patients, with a specif model for
      assessment, orientation plan, nursing care plan and evolution, was followed by
      the preparation of an orientation guide to be used by nurses, so an uniformed way
      of registration could be obtained.

PMID- 28746510
TI  - [Human leptospirosis - infection in inhabitants of the Aricanduva river valley,
      Sao Paulo city, Brazil, 1984-5; part. 1 - aspects related to the studied group
      and the environment].
AB  - The article approachs the investigation, from the epidemiological point of view,
      of one zone that had been flooded in 1983 by the Aricanduva river and its
      tributaries in the east side of the Sao Paulo city, Brazil. At that time, zone
      was affected by human leptospirosis, confirmed by laboratory tests. For the
      present survey, a population of 61 inhabitants of the region, who dwelled with
      subjects affected by leptospirosis was studied, in order to establish the level
      of infection of leptospira remaining in that population. In this paper, the
      author describes the aspects relatives to the studied group and their
      environment. It was found that eighteen months after the 1983 outbreak of the
      disease (1984-5) there still persisted in the environment, risk factors of
      leptospirotic infection such as floods and the presence of rats. In a next paper,
      the author will describe the sorological aspects of this investigation.

PMID- 28746511
TI  - [Patients with adquired mouth, nose and ear affections: basic needs altered and
      expectations concerning nursing care].
AB  - The study identifies the most basic human needs commonly altered on patients with
      adquired mouth, nose and ear affections, their expectations concerning nursing
      procedures and the relation of those expectations to the expressixe and
      instrumental roles of the nurse.

PMID- 28746512
TI  - [Iatrogeny in intensive care nursing: multidimensional analysis: previous note].
AB  - The nursing care in intensive care unit is to recover vital functions with
      maximum security. Iatrogenic accidents may occur and they will bring many
      injuries to patient. The number of registered occurence is lower than the
      incidence that implies on risk factor with interference in the care of critical
      patient. Iatrogenesis is derived from "iatros" as doctor and "genesis" as
      original. The term has been used amply to identify harmful actions. LACAZ et
      alii3 wrote iatrogenic illness is propagated by doctors, assistants,
      pharmaceutical and nurses. In relation to nursing the iatrogenic illness is
      derived to: drug administration in incorrect administration, burn by hot pouch,
      hemorrhage because disconnection of catheters, asphyxia by endotraqueal
      obstruction, fractures and trauma consequece of fall and others1,2. OGUISSO5
      studied legal aspects of nursing record and obtained, in decrescent order: fall
      of bed, change drug administration, burn, hemorhage as vigilance fault,
      nasogastric ectopic catheter, change of children. She concluded that the events
      are grave, there were incorrect recording and without rubric. These incidents
      will be more possible to occur in special units where there are critical patients
      with sophisticated procedures like the intensive care units. Many questions will
      be asked: how many times the incidents occured in those units? What are risk
      factors associated with these occurence? In this projects, we will study the
      conditions that they occured, analysis with sistemic approach and determine risk
      factors inherent in the iatrogenic illness and other connections.

PMID- 28746513
TI  - [Characteristics of the nursing instructor which facilitate the process of
      becoming a nurse. Preliminary note].
AB  - Our experience as nursing educator allows us to affirm that, as a general rule,
      there is a constant concern on that part of nursing teachers from the various
      schools and universities for the formation of the future professionals. Thus,
      with the purpose of improving the quality of teaching, these educations
      continually analyze and evaluate their programs, planning and implementing new or
      different theoretical and practical activities. However, notwithstanding that
      concern, we have observed that the professional behaviour of most of staff RN's,
      especially those recent graduated, does not reflect much of what was taught to
      them in nursing school. Often staff, nurses manifest dissatisfaction with their
      professional practice, although little or nothing seems to be done by them in
      order to change their professional reality and obtain self-achievement. Without
      any doubt, there are countless number of factors intervening and determining the
      above outlined situation, but, certainly one of them is the quality that these
      nurses attribute to the different learning situations experienced by them while
      students in their nursing programs. The person of the nursing instructor is
      always a relevant component in these situations. It is inquestionable that the
      nursing teacher, as any teacher, exerts a great influence upon the quality of the
      learning experiences of his students, as well as upon their lifes. By way of his
      attitude towards the educational process, particularly with respect to the
      subject of this process - the student - the teacher may, or may not, contribute
      in a consistent and significant way to the emotional maturation and to the
      personal and professional growth of this students, facilitating, therefore, the
      process by which these students become professionals. The lack of studies done in
      our midst on these fundamentals aspects of the nursing teaching - learning
      process, seems to indicate that, in general, nursing teacher confer a greater
      importance to the quality of teaching thin to the quality of learning. Concerned
      with these observations in a time which we consider critical for professional
      nursing in Brazil, we have been intensely motivated to identify the
      characteristics of the nursing teacher that enriches the student's learning
      experiences, and, consequently, facilitate to him the process of becoming a
      nurse.

PMID- 28746514
TI  - Experience of mothers of premature babies from birth to discharge: notes of field
      journals.
AB  - Objective: To describe the maternal care process mediated by nurses during the
      period of hospitalisation and discharge of premature babies. Method: This is a
      descriptive, exploratory, and qualitative study, using the methodological
      framework of convergent care research, with seven mothers of premature babies
      admitted to a hospital in southern Brazil, from October to December 2011. Data
      from the mother's daily journals were submitted to content analysis. Results:
      Analysis resulted in three categories portraying the path and the adaptation
      process of the mothers to the care of their premature babies, from preparation
      for discharge to overcoming her fears and insecurities concerning home care.
      Conclusion: It is important for mothers in this initial and critical stage of
      hospitalisation of preterm infants to receive assistance, especially in terms of
      receptiveness and ongoing care, as a strategy to promote maternal autonomy and
      home adaptation.

PMID- 28746515
TI  - Analysis of intensity, sensory and affective aspects of pain of patients in
      immediate postoperative care.
AB  - Objective: To evaluate the pain of patients in the immediate postoperative period
      during admission, an hour after admission, and at discharge of the post
      anesthesia care unit in terms of intensity, and sensory and affective aspects.
      Methods: Analytical, cross-sectional study with 336 patients. Data were collected
      using a sociodemographic and clinical form, the Numeric Pain Rating Scale, and
      the short-form McGill Pain Questionnaire. Data collection occurred from September
      to October 2015 at the post-anesthesia care unit of a general hospital in the
      north-west of Rio Grande do Sul, Brazil. The significance level of the
      descriptive and statistical analyses was set at p<0.05. Results: According to the
      data, 57.3% of the patients did not report pain and 47% felt pain from admission
      to discharge. Patients submitted to cancer and trauma surgeries reported more
      pain (p<0.01). At admission and maintenance, there was a prevalence of moderate
      and intense pain, and at discharge, a predominance of mild and moderate pain.
      Conclusions: The results showed a high percentage of patients with pain in the
      immediate postoperative period from admission to discharge. These findings can
      encourage researchers and health workers to conduct further investigations with
      the larger number of patients to allow for inferences.

PMID- 28746516
TI  - Lifestyles: social representations construed by patients with myocardial
      infarction and family members.
AB  - Objective: The social representations of lifestyles construed by family members
      and patients diagnosed with myocardial infarction. Method: Exploratory
      qualitative study supported by the theory of social representations, with 70
      patients and 70 family members of two Portuguese hospitals, one on the coast and
      one inland from January to June 2015. Structural analysis was performed using two
      questionnaires relying on the technique called Free Association of Words.
      Results: The evocations of patients and family members indicated weak convergence
      between the two groups in representing Lifestyle, yet showed the existence of
      knowledge that enhances a healthy lifestyle. Conclusions: The categories Eat and
      Change were a consensus among the groups. For patients and family members, it was
      consensual that a poor diet is a harmful lifestyle for health. It was also clear
      that change is fundamental. Such an assumption makes room for the intervention of
      health professionals.

PMID- 28746517
TI  - Ambiguity of care in the experience of drug consumers.
AB  - Objective: To understand the perception of users of a Psychosocial Care Center
      about care in the context of drug use. Methods: Study based on the Phenomenology
      of Maurice Merleau-Ponty, developed in the Center for Psychosocial Care Alcohol
      and Other Drugs. The data has been submitted to the Analytical Technique of
      Ambiguity. Results: The drug use sometimes provides the consumer with pleasurable
      feelings, sometimes contributing to the occurrence of biopsychosocial harm and/or
      new possibilities for relationship with the drug. Conclusions: The drug use is an
      ambiguous process, which corresponds to the perception of different care profiles
      in the relationship between the consumer and the drug. It is up to the health
      professionals to recognize the diverse possibilities of care and to favor the
      construction of therapeutic projects based on listening and respecting the needs
      of drug users.

PMID- 28746518
TI  - Interruptions and their effects on the dynamics of the nursing work.
AB  - Objectives: To investigate the nurses' perception about interruptions during the
      workflow and their implications on the professional practice environment.
      Methods: A survey was conducted with 133 nurses in a school hospital in the state
      of Sao Paulo from October 2015 to March 2016, through the use of a self
      administered questionnaire. For data analysis, Chi-square and Fischer tests have
      been used. Results: Most of the nurses have reported frequent and recurring
      interruptions during their work activities. The interruptive processes are more
      frequent during the documentation process (n=118; 91.5%) and guidance to the
      patient/family (n=58; 45%). They are caused by the ringing of the phone (n=114;
      87%), and by problem solving in the unit (n=107; 81.7%). Conclusions: According
      to the nurses' opinion, the interruptive processes have repercussions on the
      working dynamics, on the caring process and on the patient's safety.

PMID- 28746519
TI  - Single Derivation Fragmented QRS Can Predict Poor Prognosis in Successfully
      Revascularized Acute STEMI Patients.
AB  - BACKGROUND: QRS fragmentation (fQRS) is classically defined as the presence of
      slurred QRS morphology in at least two contiguous leads, and its prognostic
      importance has been shown in ST elevation myocardial infarction (STEMI). However,
      no study has investigated the significance of single lead fQRS (sl-fQRS) in
      surface electrocardiography (ECG). OBJECTIVES: To evaluate whether sl-fQRS is as
      valuable as classical fQRS in patients with acute STEMI who had successful
      revascularization with primary percutaneous coronary intervention (pPCI).
      METHODS: We included 330 patients with a first STEMI who had been successfully
      revascularized with pPCI. The patient's electrocardiography was obtained in the
      first 48 hours, and the patients were divided into three groups according to the
      absence of fQRS (no-fQRS); fQRS presence in a single lead (sl-fQRS); and >=2
      leads with fQRS (classical fQRS). RESULTS: In-hospital mortality was
      significantly higher both in patients with sl-fQRS and in patients with >= 2
      leads with fQRS compared to patients with no-fQRS. In ROC curve analysis, >= 1
      leads with fQRS yielded a sensitivity of 75% and specificity of 57.4% for the
      prediction of in-hospital mortality. Multivariate analysis showed that sl-fQRS is
      an independent predictor of in-hospital mortality (OR: 3.989, 95% CI: 1.237
      12.869, p = 0.021). CONCLUSIONS: Although the concept of at least two derivations
      is mentioned for the classical definition of fQRS, our study showed that fQRS in
      only one lead is also associated with poor outcomes. Therefore, >=1 leads with
      fQRS can be useful when describing the patients under high cardiac risk in acute
      STEMI.

PMID- 28746520
TI  - Relationship between Cardiometabolic Parameters and Elevated Resting and Effort
      Heart Rate in Schoolchildren.
AB  - Background: Little has been studied on heart rate and its relationship with
      metabolic disorders. Objective: To identify possible association between heart
      rate (HR) and metabolic disorders in children and adolescents. Methods: This
      cross-sectional study evaluated 2.098 subjects, aged between 7 and 17 years. The
      variables evaluated were: HR, systolic (SBP) and diastolic blood pressure (DBP),
      pulse pressure (PP), double-product (DP), myocardial oxygen consumption (mVO2),
      lipids, glucose and uric acid levels, body mass index (BMI) and waist
      circumference (WC). The values of HR at rest and effort were divided into
      quartiles. The association between continuous values of HR and cardiometabolic
      indicators was tested by linear regression. Results: LDL cholesterol presented a
      significantly higher mean (p = 0.003) in schoolchildren with resting HR greater
      or equal to 91 bpm, compared to students with less than 75 bpm. Compared with the
      quartiles of effort HR, SBP, DBP, glucose and uric acid presented high values
      when HR was greater or equal than 185 bpm. SBP, glucose and HDL cholesterol
      demonstrated a significant association with resting HR. Uric acid was observed as
      a predictor of increased effort HR. Conclusion: Schoolchildren with a higher
      resting HR have higher mean of LDL cholesterol. For effort HR, there was an
      increase in blood pressure, glucose and uric acid levels. Uric acid has been
      shown to be a predictor of elevated effort HR.

PMID- 28746521
TI  - Playful Interventions Increase Knowledge about Healthy Habits and Cardiovascular
      Risk Factors in Children: The CARDIOKIDS Randomized Study.
AB  - BACKGROUND: Childhood obesity is an important health problem worldwide. In this
      context, there is a need for the development and evaluation of innovative
      educational interventions targeting prevention and formation of health habits.
      OBJECTIVES: To ascertain the impact of ludic workshops on children's knowledge,
      self-care, and body weight. METHODS: This was a randomized, clinical study with
      79 students aged 7-11 years, conducted from March to November 2012.
      Anthropometric measurements were collected and two questionnaires (Typical Day of
      Physical Activities and Food Intake, in Portuguese, and the CARDIOKIDS, a
      questionnaire of knowledge about cardiovascular risk factors) were applied at
      baseline, at the end of intervention, and three months thereafter. The
      intervention consisted of eight playful workshops, which involved the
      presentation of a play. RESULTS: Seventy-nine students were randomized to the
      intervention (n = 40) or the control group (n = 39). Mean age was 10.0 +/- 1.1
      years. After eight weeks, the intervention group showed significant improvement
      in the knowledge score (p < 0.001). There was an increase in physical activity
      scores in both groups, but with no difference between the groups at the end of
      intervention (p = 0.209). A reduction in the BMI percentile was observed in the
      intervention group, but there was no significant statistical difference between
      the two groups after the intervention. CONCLUSIONS: Playful interventions may
      improve knowledge and physical activity levels in children and, when combined
      with other strategies, may be beneficial to prevent child obesity and improve
      self-care.

PMID- 28746522
TI  - BTA distance learning course in pulmonology.

PMID- 28746523
TI  - The paradox of asthma: neglect, burden, and big data.

PMID- 28746524
TI  - Opaque hemithorax.

PMID- 28746525
TI  - Subgroup analysis and interaction tests: why they are important and how to avoid
      common mistakes.

PMID- 28746526
TI  - The impact of asthma in Brazil: a longitudinal analysis of data from a Brazilian
      national database system.
AB  - Objective:: To present official longitudinal data on the impact of asthma in
      Brazil between 2008 and 2013. Methods:: This was a descriptive study of data
      collected between 2008 and 2013 from an official Brazilian national database,
      including data on asthma-related number of hospitalizations, mortality, and
      hospitalization costs. A geographical subanalysis was also performed. Results::
      In 2013, 2,047 people died from asthma in Brazil (5 deaths/day), with more than
      120,000 asthma-related hospitalizations. During the whole study period, the
      absolute number of asthma-related deaths and of hospitalizations decreased by 10%
      and 36%, respectively. However, the in-hospital mortality rate increased by
      approximately 25% in that period. The geographic subanalysis showed that the
      northern/northeastern and southeastern regions had the highest asthma-related
      hospitalization and in-hospital mortality rates, respectively. An analysis of the
      states representative of the regions of Brazil revealed discrepancies between the
      numbers of asthma-related hospitalizations and asthma-related in-hospital
      mortality rates. During the study period, the cost of asthma-related
      hospitalizations to the public health care system was US$ 170 million.
      Conclusions:: Although the numbers of asthma-related deaths and hospital
      admissions in Brazil have been decreasing since 2009, the absolute numbers are
      still high, resulting in elevated direct and indirect costs for the society. This
      shows the relevance of the burden of asthma in middle-income countries.
      Objetivo:: Apresentar dados longitudinais oficiais sobre o impacto da asma no
      Brasil entre 2008 e 2013. Metodos:: Estudo descritivo de dados extraidos de um
      banco de dados do governo brasileiro entre 2008 e 2013, no qual foram analisados
      as hospitalizacoes e obitos por asma, bem como o custo das hospitalizacoes. Foi
      tambem realizada uma subanalise geografica. Resultados:: Em 2013, 2.047 pessoas
      morreram de asma no Brasil (5 obitos/dia), com mais de 120.000 hospitalizacoes
      por asma. Durante o periodo de estudo, o numero absoluto de obitos e
      hospitalizacoes por asma diminuiu 10% e 36%, respectivamente. No entanto, a taxa
      de mortalidade hospitalar aumentou aproximadamente 25%. A subanalise geografica
      mostrou que as regioes Norte/Nordeste e Sudeste apresentaram as maiores taxas de
      hospitalizacao e mortalidade hospitalar por asma, respectivamente. A analise dos
      estados representativos de cada regiao mostrou discrepancias entre as
      hospitalizacoes por asma e as taxas de mortalidade hospitalar por asma. Durante o
      periodo de estudo, as hospitalizacoes por asma custaram US$ 170 milhoes ao
      sistema publico de saude. Conclusoes:: Embora os obitos e hospitalizacoes por
      asma no Brasil estejam diminuindo desde 2009, os numeros absolutos ainda sao
      altos, com elevados custos diretos e indiretos para a sociedade, o que mostra a
      relevancia do impacto da asma em paises de renda media.

PMID- 28746527
TI  - Sleep-disordered breathing in patients with COPD and mild hypoxemia: prevalence
      and predictive variables.
AB  - Objective:: To infer the prevalence and variables predictive of isolated
      nocturnal hypoxemia and obstructive sleep apnea (OSA) in patients with COPD and
      mild hypoxemia. Methods:: This was a cross-sectional study involving clinically
      stable COPD outpatients with mild hypoxemia (oxygen saturation = 90-94%) at a
      clinical center specializing in respiratory diseases, located in the city of
      Goiania, Brazil. The patients underwent clinical evaluation, spirometry,
      polysomnography, echocardiography, arterial blood gas analysis, six-minute walk
      test assessment, and chest X-ray. Results:: The sample included 64 patients with
      COPD and mild hypoxemia; 39 (61%) were diagnosed with sleep-disordered breathing
      (OSA, in 14; and isolated nocturnal hypoxemia, in 25). Correlation analysis
      showed that PaO2 correlated moderately with mean sleep oxygen saturation (r =
      0.45; p = 0.0002), mean rapid eye movement (REM) sleep oxygen saturation (r =
      0.43; p = 0.001), and mean non-REM sleep oxygen saturation (r = 0.42; p = 0.001).
      A cut-off point of PaO2 <= 70 mmHg in the arterial blood gas analysis was
      significantly associated with sleep-disordered breathing (OR = 4.59; 95% CI: 1.54
      13.67; p = 0.01). The model showed that, for identifying sleep-disordered
      breathing, the cut-off point had a specificity of 73.9% (95% CI: 51.6-89.8%), a
      sensitivity of 63.4% (95% CI: 46.9-77.9%), a positive predictive value of 81.3%
      (95% CI: 67.7-90.0%), and a negative predictive value of 53.1% (95% CI: 41.4
      64.4%), with an area under the ROC curve of 0.69 (95% CI: 0.57-0.80), correctly
      classifying the observations in 67.2% of the cases. Conclusions:: In our sample
      of patients with COPD and mild hypoxemia, the prevalence of sleep-disordered
      breathing was high (61%), suggesting that such patients would benefit from sleep
      studies. Objetivo:: Inferir a prevalencia e as variaveis preditivas de hipoxemia
      noturna e apneia obstrutiva do sono (AOS) em pacientes portadores de DPOC com
      hipoxemia leve. Metodos:: Estudo transversal realizado em pacientes
      ambulatoriais, clinicamente estaveis, portadores de DPOC e hipoxemia leve
      (saturacao de oxigenio = 90-94%) em um centro clinico especializado no
      atendimento de doencas respiratorias em Goiania (GO). Os pacientes foram
      submetidos a avaliacao clinica, espirometria, polissonografia, ecocardiografia,
      gasometria arterial, teste de caminhada de seis minutos e radiografia de torax.
      Resultados:: Foram avaliados 64 pacientes com DPOC e hipoxemia leve, e 39 (61%)
      apresentaram disturbios respiratorios do sono (14 com AOS e 25 com hipoxemia
      noturna isolada). A analise de correlacao mostrou moderada correlacao da PaO2 com
      saturacao media do sono (r = 0,45; p = 0,0002), saturacao media do sono rapid eye
      movement (REM; r = 0,43; p = 0,001) e saturacao media do sono nao-REM (r = 0,42;
      p = 0,001). Um ponto de corte de PaO2 <= 70 mmHg (OR = 4,59; IC95%: 1,54-13,67; p
      = 0,01) na gasometria arterial foi significativamente associada com disturbios
      respiratorios do sono. O modelo mostrou que, para identificar disturbios
      respiratorios do sono, o ponto de corte teve uma especificidade de 73,9% (IC95%:
      51,6-89,8%), uma sensibilidade de 63,4% (IC95%: 46,9-77,9%) e valores preditivos
      positivo e negativo de 81,3% (IC95%: 67,7-90,0%) e 53,1% (IC95%: 41,4-64,4%),
      respectivamente. A area sob a curva ROC foi de 0,69 (IC95%: 0,57-0,80), e a
      proporcao de observacoes corretamente classificadas foi de 67,2% dos casos.
      Conclusoes:: A elevada prevalencia de disturbios respiratorios do sono em
      portadores de DPOC e hipoxemia leve nesta amostra (61%) sugere que esses
      pacientes podem se beneficiar da realizacao de estudos do sono.

PMID- 28746528
TI  - Simple motor tasks independently predict extubation failure in critically ill
      neurological patients.
AB  - Objective:: To evaluate the usefulness of simple motor tasks such as hand
      grasping and tongue protrusion as predictors of extubation failure in critically
      ill neurological patients. Methods:: This was a prospective cohort study
      conducted in the neurological ICU of a tertiary care hospital in the city of
      Porto Alegre, Brazil. Adult patients who had been intubated for neurological
      reasons and were eligible for weaning were included in the study. The ability of
      patients to perform simple motor tasks such as hand grasping and tongue
      protrusion was evaluated as a predictor of extubation failure. Data regarding
      duration of mechanical ventilation, length of ICU stay, length of hospital stay,
      mortality, and incidence of ventilator-associated pneumonia were collected.
      Results:: A total of 132 intubated patients who had been receiving mechanical
      ventilation for at least 24 h and who passed a spontaneous breathing trial were
      included in the analysis. Logistic regression showed that patient inability to
      grasp the hand of the examiner (relative risk = 1.57; 95% CI: 1.01-2.44; p <
      0.045) and protrude the tongue (relative risk = 6.84; 95% CI: 2.49-18.8; p <
      0.001) were independent risk factors for extubation failure. Acute Physiology and
      Chronic Health Evaluation II scores (p = 0.02), Glasgow Coma Scale scores at
      extubation (p < 0.001), eye opening response (p = 0.001), MIP (p < 0.001), MEP (p
      = 0.006), and the rapid shallow breathing index (p = 0.03) were significantly
      different between the failed extubation and successful extubation groups.
      Conclusions:: The inability to follow simple motor commands is predictive of
      extubation failure in critically ill neurological patients. Hand grasping and
      tongue protrusion on command might be quick and easy bedside tests to identify
      neurocritical care patients who are candidates for extubation. Objetivo:: Avaliar
      a utilidade de tarefas motoras simples, tais como preensao de mao e protrusao da
      lingua, para predizer extubacao malsucedida em pacientes neurologicos criticos.
      Metodos:: Estudo prospectivo de coorte realizado na UTI neurologica de um
      hospital terciario em Porto Alegre (RS). Pacientes adultos que haviam sido
      intubados por motivos neurologicos e que eram candidatos ao desmame foram
      incluidos no estudo. O estudo avaliou se a capacidade dos pacientes de realizar
      tarefas motoras simples como apertar as maos do examinador e por a lingua para
      fora seria um preditor de extubacao malsucedida. Foram coletados dados referentes
      ao tempo de ventilacao mecanica, tempo de internacao na UTI, tempo de internacao
      hospitalar, mortalidade e incidencia de pneumonia associada a ventilacao
      mecanica. Resultados:: Foram incluidos na analise 132 pacientes intubados que
      haviam recebido ventilacao mecanica durante pelo menos 24 h e que passaram no
      teste de respiracao espontanea. A regressao logistica mostrou que a incapacidade
      dos pacientes de apertar a mao do examinador (risco relativo = 1,57; IC95%: 1,01
      2,44; p < 0,045) e de por a lingua para fora (risco relativo = 6,84; IC95%: 2,49
      18,8; p < 0,001) foram fatores independentes de risco de extubacao malsucedida.
      Houve diferencas significativas entre os pacientes nos quais a extubacao foi
      malsucedida e aqueles nos quais a extubacao foi bem-sucedida quanto a pontuacao
      obtida no Acute Physiology and Chronic Health Evaluation II (p = 0,02), pontuacao
      obtida na Escala de Coma de Glasgow no momento da extubacao (p < 0,001), abertura
      dos olhos em resposta ao comando (p = 0,001), PImax (p < 0,001), PEmax (p =
      0,006) e indice de respiracao rapida e superficial (p = 0,03). Conclusoes:: A
      incapacidade de obedecer a comandos motores simples e preditora de extubacao
      malsucedida em pacientes neurologicos criticos. Preensao de mao e protrusao da
      lingua em resposta ao comando podem ser testes rapidos e faceis realizados a
      beira do leito para identificar pacientes neurologicos criticos que sejam
      candidatos a extubacao.

PMID- 28746529
TI  - Ultrasound-guided intrapleural positioning of pleural catheters: influence on
      immediate lung expansion and pleurodesis in patients with recurrent malignant
      pleural effusion.
AB  - Objective:: To evaluate the role of intrapleural positioning of a pleural
      catheter in early lung expansion and pleurodesis success in patients with
      recurrent malignant pleural effusion (RMPE). Methods:: This was a retrospective
      study nested into a larger prospective cohort study including patients with RMPE
      recruited from a tertiary university teaching hospital between June of 2009 and
      September of 2014. The patients underwent pleural catheter insertion followed by
      bedside pleurodesis. Chest CT scans were performed twice: immediately before
      pleurodesis (iCT) and 30 days after pleurodesis (CT30). Catheter positioning was
      categorized based on iCT scans as posterolateral, anterior, fissural, and
      subpulmonary. We used the pleural volume on iCT scans to estimate early lung
      expansion and the difference between the pleural volumes on CT30 and iCT scans to
      evaluate radiological success of pleurodesis. Clinical pleurodesis success was
      defined as no need for any other pleural procedure. Results:: Of the 131 eligible
      patients from the original study, 85 were included in this nested study (64
      women; mean age: 60.74 years). Catheter tip positioning was subpulmonary in 35
      patients (41%), anterior in 23 (27%), posterolateral in 17 (20%), and fissural in
      10 (12%). No significant differences were found among the groups regarding early
      lung expansion (median residual pleural cavity = 377 mL; interquartile range: 171
      722 mL; p = 0.645), radiological success of pleurodesis (median volume = 33 mL;
      interquartile range: -225 to 257 mL; p = 0.923), and clinical success of
      pleurodesis (85.8%; p = 0.676). Conclusions:: Our results suggest that the
      position of the tip of the pleural catheter influences neither early lung
      expansion nor bedside pleurodesis success in patients with RMPE. Objetivo::
      Avaliar o papel do posicionamento intrapleural do cateter pleural na expansao
      pulmonar precoce e no sucesso da pleurodese em pacientes com derrame pleural
      maligno recorrente (DPMR). Metodos:: Trata-se de um estudo retrospectivo aninhado
      em um estudo prospectivo de coorte maior com pacientes com DPMR recrutados em um
      hospital-escola universitario terciario entre junho de 2009 e setembro de 2014.
      Os pacientes foram submetidos a insercao de cateter pleural e, em seguida,
      pleurodese a beira do leito. A TC de torax foi realizada duas vezes:
      imediatamente antes da pleurodese (TCi) e 30 dias apos a pleurodese (TC30). Com
      base na TCi, a posicao do cateter foi classificada em posterolateral, anterior,
      fissural e subpulmonar. Usamos o volume pleural na TCi para estimar a expansao
      pulmonar precoce e a diferenca entre os volumes pleurais na TC30 e na TCi a fim
      de avaliar o sucesso radiologico da pleurodese. Considerou-se que a pleurodese
      teve exito clinico quando nao foi necessario realizar nenhum outro procedimento
      pleural. Resultados:: Dos 131 pacientes elegiveis do estudo original, 85 foram
      incluidos neste estudo aninhado (64 mulheres; media de idade: 60,74 anos). A
      posicao da ponta do cateter foi subpulmonar em 35 pacientes (41%), anterior em 23
      (27%), posterolateral em 17 (20%) e fissural em 10 (12%). Nao houve diferencas
      significativas entre os grupos quanto a expansao pulmonar precoce (mediana da
      cavidade pleural residual = 377 ml; intervalo interquartil: 171-722 ml; p =
      0,645), sucesso radiologico da pleurodese (mediana do volume = 33 ml; intervalo
      interquartil: -225 a 257 ml; p = 0,923) e sucesso clinico da pleurodese (85,8%; p
      = 0,676). Conclusoes:: Nossos resultados sugerem que a posicao da ponta do
      cateter pleural nao influencia nem a expansao pulmonar precoce nem o sucesso da
      pleurodese a beira do leito em pacientes com DPMR.

PMID- 28746530
TI  - Hearing thresholds in patients with drug-resistant tuberculosis: baseline
      audiogram configurations and associations.
AB  - Objective:: To use baseline audiogram parameters in order to ascertain whether
      drug-resistant tuberculosis (DR-TB) has effects on hearing, as well as to
      describe the configurations of the audiograms and to determine whether there are
      parameters that can be associated with those configurations. Methods:: This was a
      prospective study involving patients diagnosed with DR-TB at a tuberculosis
      treatment center in the state of Ogun, in Nigeria. The patients included in the
      study were submitted to pure tone audiometry at baseline (within two weeks after
      treatment initiation). For comparative analyses, data regarding demographic and
      clinical characteristics were collected from the medical records of the patients.
      Results:: The final sample comprised 132 patients. The mean age of the patients
      was 34.5 +/- 12.6 years (range, 8-82 years), and the male:female ratio was 2:1.
      Of the 132 patients, 103 (78.0%) resided in neighboring states, 125 (94.7%) had
      previously experienced antituberculosis treatment failure, and 18 (13.6%) were
      retroviral-positive. Normal audiograms were found in 12 patients (9.1%), whereas
      sensorineural hearing loss was identified in 104 (78.8%), the two most common
      configurations being ascending, in 54 (40.9%), and sloping, in 26 (19.7%). Pure
      tone averages at low frequencies (0.25-1.0 kHz) and high frequencies (2.0-8.0
      kHz) were 33.0 dB and 40.0 dB, respectively. Regarding the degree of hearing loss
      in the better ear, 36 patients (27.3%) were classified as having normal hearing
      and 67 (50.8%) were classified as having mild hearing loss (26-40 dB), whereas 29
      (21.9%) showed moderate or severe hearing loss. Among the variables studied (age,
      gender, retroviral status, previous treatment outcome, and weight at admission),
      only male gender was associated with audiometric configurations. Conclusions:: In
      this sample of patients with DR-TB, most presented with bilateral, mild,
      suboptimal sensorineural hearing loss, and ascending/sloping audiometric
      configurations were associated with male gender. Objetivo:: Utilizar parametros
      do audiograma basal para verificar se a tuberculose resistente (TB-R) tem efeitos
      na audicao, descrever as configuracoes dos audiogramas e determinar se ha
      parametros que possam ser associados a essas configuracoes. Metodos:: Estudo
      prospectivo com pacientes diagnosticados com TB-R em um centro de tratamento de
      tuberculose no estado de Ogun, Nigeria. Os pacientes incluidos no estudo foram
      submetidos a audiometria de tons puros em ate duas semanas apos o inicio do
      tratamento (audiometria basal). Caracteristicas demograficas e clinicas foram
      coletadas dos prontuarios medicos dos pacientes para analises comparativas.
      Resultados:: A amostra final envolveu 132 pacientes. A media de idade dos
      pacientes foi de 34,5 +/- 12,6 anos (variacao, 8-82 anos), e a razao homem:mulher
      foi de 2:1. A maioria dos pacientes (n = 103; 78,0%) residia nos estados vizinhos
      e tinha historia de falha de tratamento antituberculose (n = 125; 94.7%); 18
      (13.6%) apresentavam status retroviral positivo. Doze pacientes (9,1%)
      apresentaram audiogramas normais, e 104 (78,8%) apresentaram perda auditiva
      neurossensorial, sendo as configuracoes mais comuns do tipo ascendente, em 54
      (40,9%), e descendente, em 26 (19,7%). As medias de tons puros em frequencias
      baixas (0,25-1,0 kHz) e altas (2,0-8,0 kHz) foram de 33,0 dB e 40,0 dB,
      respectivamente. Quanto ao grau de perda auditiva no melhor ouvido, 36 pacientes
      (27,3%) apresentaram audicao normal, e 67 (50,8%) apresentaram perda auditiva
      leve (26-40 dB), enquanto 29 (21,9%) mostraram perda auditiva moderada ou grave.
      Entre as variaveis estudadas (idade, genero, status retroviral, desfecho de
      tratamento anterior e peso na admissao), somente o genero masculino foi associado
      as configuracoes audiometricas. Conclusoes:: Nesta amostra de pacientes com TB-R,
      a maioria apresentou perda auditiva neurossensorial leve e subotima
      bilateralmente, com configuracoes audiometricas ascendentes/descendentes
      associadas ao genero masculino.

PMID- 28746531
TI  - Effective tobacco control measures: agreement among medical students.
AB  - Objective:: To determine the level of agreement with effective tobacco control
      measures recommended by the World Health Organization and to assess the attitudes
      toward, knowledge of, and beliefs regarding smoking among third-year medical
      students at University of Sao Paulo School of Medicine, located in the city of
      Sao Paulo, Brazil. Methods:: Between 2008 and 2012, all third-year medical
      students were invited to complete a self-administered questionnaire based on the
      Global Health Professionals Student Survey and its additional modules. Results::
      The study sample comprised 556 students. The level of agreement with the World
      Health Organization recommendations was high, except for the components "received
      smoking cessation training" and "raising taxes is effective to reduce the
      prevalence of smoking". Most of the students reported that they agree with
      banning tobacco product sales to minors (95%), believe that physicians are role
      models to their patients (84%), and believe that they should advise their
      patients to quit cigarette smoking (96%) and using other tobacco products (94%).
      Regarding smoking cessation methods, most of the students were found to know more
      about nicotine replacement therapy than about non-nicotine therapies (93% vs.
      53%). Only 37% of the respondents were aware of the importance of educational
      antismoking materials, and only 31% reported that they believe in the
      effectiveness of encouraging their patients, during medical visits. In our
      sample, the prevalence of current cigarette smoking was 5.23%; however, 43.82% of
      the respondents reported having experimented with water-pipe tobacco smoking.
      Conclusions:: Our results revealed the need to emphasize to third-year medical
      students the importance of raising the prices of and taxes on tobacco products.
      We also need to make students aware of the dangers of experimenting with tobacco
      products other than cigarettes, particularly water-pipe tobacco smoking.
      Objetivo:: Determinar o grau de concordancia com medidas eficazes de controle do
      tabaco recomendadas pela Organizacao Mundial da Saude e avaliar as atitudes, o
      conhecimento e as crencas a respeito do tabagismo em alunos do terceiro ano de
      medicina da Faculdade de Medicina da Universidade de Sao Paulo, em Sao Paulo
      (SP). Metodos:: Entre 2008 e 2012, todos os alunos do terceiro ano de medicina
      foram convidados a preencher um questionario autoaplicavel baseado na Global
      Health Professions Student Survey e em seus modulos adicionais. Resultados:: A
      amostra consistiu em 556 estudantes. O grau de concordancia com as recomendacoes
      da Organizacao Mundial da Saude foi alto, a excecao de "receberam treinamento a
      respeito de cessacao do tabagismo" e "aumentar os impostos e uma medida eficaz
      para reduzir a prevalencia do tabagismo". A maioria dos estudantes relatou que
      concorda com a proibicao da venda de produtos do tabaco a menores de idade (95%),
      acredita que os medicos sao modelos de comportamento para seus pacientes (84%) e
      acredita que deveriam aconselhar seus pacientes a parar de fumar cigarros (96%) e
      de usar outros produtos do tabaco (94%). No tocante aos metodos de cessacao do
      tabagismo, observamos que a maioria dos estudantes sabe mais sobre terapia de
      reposicao da nicotina do que sobre terapias nao nicotinicas (93% vs. 53%). Apenas
      37% dos participantes estavam cientes da importancia de material educacional
      antitabagismo, e apenas 31% relataram que acreditam na eficacia de incentivar
      seus pacientes, durante as consultas medicas, a parar de fumar. Em nossa amostra,
      a prevalencia de tabagismo atual foi de 5,23%; entretanto, 43,82% dos
      participantes relataram ter experimentado fumar tabaco com um narguile.
      Conclusoes:: Nossos resultados revelaram a necessidade de deixar claro para os
      alunos do terceiro ano de medicina o quao importante e aumentar os precos e
      impostos dos produtos do tabaco. E tambem preciso conscientizar os alunos dos
      perigos de experimentar outros produtos do tabaco que nao os cigarros,
      particularmente o narguile.

PMID- 28746532
TI  - Effects of emissions from sugar cane burning on the trachea and lungs of Wistar
      rats.
AB  - Objective:: To evaluate the effects of exposure to emissions from sugar cane
      burning on inflammatory mechanisms in tissues of the trachea and lung parenchyma
      in Wistar rats after different periods of exposure. Methods:: This was an
      experimental open randomized study. The animals were divided into four groups: a
      control group (CG) underwent standard laboratory conditions, and three
      experimental groups were exposed to emissions from sugar cane burning over
      different periods of time, in days-1 (EG1), 7 (EG7), and 21 (EG21). After
      euthanasia with 200 mg/kg of ketamine/xylazine, fragments of trachea and lung
      were collected and fixed in 10% formalin. Histological analyses were performed
      with H&E and picrosirius red staining. Results:: No inflammatory infiltrates were
      found in the tissues of CG rats. The histological examination of tissues of the
      trachea and lung parenchyma revealed that the inflammatory process was
      significantly more intense in EG7 than in the CG (p < 0.05 and p < 0.01,
      respectively). In comparison with the CG and EG1, angiogenesis in the lung
      parenchyma and collagen deposition in tracheal tissues were significantly greater
      only in EG21 (p < 0.001 and p < 0.01, respectively). Conclusions:: In this
      sample, emissions from sugar cane burning induced acute focal and diffuse
      inflammation in the lamina propria of tracheal tissues, with no loss of ciliated
      epithelial tissue. In the lung parenchyma of the animals in the experimental
      groups, there was interstitial and alveolar edema, together with
      polymorphonuclear cell infiltrates. Objetivo:: Avaliar os efeitos da exposicao a
      fumaca da queima da cana-de-acucar sobre mecanismos inflamatorios em tecidos de
      traqueia e de parenquima pulmonar de ratos Wistar apos diferentes periodos de
      exposicao. Metodos:: Estudo experimental, randomizado, nao cego. Os animais foram
      divididos em quatro grupos: controle (GC), sob condicoes padrao de laboratorio e
      os demais expostos a fumaca da queima da cana-de-acucar por diferentes periodos:
      em 1 (GE1), 7 (GE7) e 21 (GE21) dias. Apos a eutanasia com 200 mg/kg de
      ketamina/xilazina, foram coletados fragmentos de traqueia e pulmao e fixadas em
      formol 10%. Analises histologicas foram realizadas com coloracao com H&E e
      picrosirius. Resultados:: Nao houve infiltrado inflamatorio nos tecidos no GC. O
      processo inflamatorio na analise histologica de tecidos de traqueia e de
      parenquima pulmonar foi significativamente mais intenso no GE7 quando comparado
      ao GC (p < 0,05 e p < 0,01, respectivamente). Em comparacao com os grupos GC e
      GE1, apenas no GE21 foi observada angiogenese significativa no parenquima
      pulmonar e aumento significativo de depositos de colageno em tecido de traqueia
      (p < 0,001 e p < 0,01, respectivamente). Conclusoes:: Nesta amostra, a fumaca da
      queima de cana-de-acucar induziu processo inflamatorio focal, difuso e agudo em
      tecidos de traqueia na lamina propria, sem perda do tecido epitelial ciliado.
      Houve presenca de edemas intersticiais e alveolares e infiltrados de celulas
      polimorfonucleares no parenquima pulmonar nos animais dos grupos experimentais.

PMID- 28746533
TI  - Frequency of indeterminate results from an interferon-gamma release assay among
      HIV-infected individuals.
AB  - Objective:: To evaluate the frequency of and factors associated with
      indeterminate interferon-gamma release assay (IGRA) results in people living with
      HIV/AIDS (PLWHA). Methods:: We tested 81 PLWHA in the central-west region of
      Brazil, using the tuberculin skin test and an IGRA. Information on
      sociodemographic and clinical variables was gathered through the use of
      questionnaires and from medical records. The association of those variables with
      indeterminate results was analyzed by calculating the adjusted ORs in a
      multivariate logistic regression model. Concordance was evaluated by determining
      the kappa statistic. Results:: Among the 81 patients evaluated, the tuberculin
      skin test results were positive in 18 (22.2%) of the patients, and the IGRA
      results were positive in 10 (12.3%), with a kappa of 0.62. The IGRA results were
      indeterminate in 22 (27.1%) of the patients (95% CI: 17.8-38.1%). The odds of
      obtaining indeterminate results were significantly higher in smokers (adjusted OR
      = 6.0; 95% CI: 1.4-26.7) and in samples stored for less than 35 days (adjusted OR
      = 14.0; 95% CI: 3.1-64.2). Patients with advanced immunosuppression (CD4+ T-cell
      count < 200 cells/mm3) were at a higher risk for indeterminate results (OR
      adjusted for smoking and inadequate duration of sample storage = 4.7; 95% CI:
      0.91-24.0), although the difference was not significant. Conclusions:: The high
      prevalence of indeterminate results can be a major limitation for the routine use
      of IGRAs in PLWHA. The need to repeat the test increases its costs and should be
      taken into account in cost-effectiveness studies. The processing of samples can
      significantly alter the results. Objetivo:: Avaliar a frequencia de resultados
      indeterminados de um interferon-gamma release assay (IGRA, ensaio de liberacao de
      interferon-gama) e os fatores relacionados com esses resultados em pessoas
      vivendo com HIV/AIDS (PVHA). Metodos:: Foram avaliadas 81 PVHA na regiao Centro
      Oeste do Brasil, por meio do teste tuberculinico e de um IGRA. Informacoes a
      respeito de variaveis sociodemograficas e clinicas foram obtidas por meio de
      questionarios e prontuarios medicos. A relacao entre essas variaveis e os
      resultados indeterminados foi avaliada por meio do calculo da OR ajustada em um
      modelo de regressao logistica multivariada. A concordancia foi avaliada por meio
      do coeficiente kappa. Resultados:: Os resultados do teste tuberculinico e do IGRA
      foram positivos em 18 (22,2%) e 10 (12,3%), respectivamente, dos 81 pacientes
      avaliados (kappa = 0,62). O resultado do IGRA foi indeterminado em 22 (27,1%) dos
      pacientes (IC95%: 17,8-38,1%). A chance de resultados indeterminados foi
      significativamente maior em fumantes (OR ajustada = 6,0; IC95%: 1,4-26,7) e em
      amostras armazenadas durante menos de 35 dias (OR ajustada = 14,0; IC95%: 3,1
      64,2). Pacientes com imunossupressao avancada (contagem de celulas T CD4+ < 200
      celulas/mm3) apresentaram maior risco de resultados indeterminados (OR ajustada
      para tabagismo e tempo inadequado de armazenamento das amostras = 4,7; IC95%:
      0,91-24,0), embora a diferenca nao tenha sido significativa. Conclusoes:: A alta
      prevalencia de resultados indeterminados pode ser um grande obstaculo ao uso
      rotineiro de IGRAs em PVHA. A necessidade de repetir o teste aumenta seu custo e
      deve ser levada em conta em estudos da relacao entre custo e eficacia. O
      processamento das amostras pode alterar significativamente os resultados.

PMID- 28746535
TI  - A storm of stones in the lungs: an uncommon sequela of varicella pneumonia.

PMID- 28746536
TI  - ?

PMID- 28746537
TI  - ?

PMID- 28746538
TI  - ?

PMID- 28746534
TI  - Brazilian guidelines for the diagnosis and treatment of cystic fibrosis.
AB  - Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by
      dysfunction of the CFTR gene. It is a multisystem disease that most often affects
      White individuals. In recent decades, various advances in the diagnosis and
      treatment of CF have drastically changed the scenario, resulting in a significant
      increase in survival and quality of life. In Brazil, the current neonatal
      screening program for CF has broad coverage, and most of the Brazilian states
      have referral centers for the follow-up of individuals with the disease.
      Previously, CF was limited to the pediatric age group. However, an increase in
      the number of adult CF patients has been observed, because of the greater number
      of individuals being diagnosed with atypical forms (with milder phenotypic
      expression) and because of the increase in life expectancy provided by the new
      treatments. However, there is still great heterogeneity among the different
      regions of Brazil in terms of the access of CF patients to diagnostic and
      therapeutic methods. The objective of these guidelines was to aggregate the main
      scientific evidence to guide the management of these patients. A group of 18 CF
      specialists devised 82 relevant clinical questions, divided into five categories:
      characteristics of a referral center; diagnosis; treatment of respiratory
      disease; gastrointestinal and nutritional treatment; and other aspects. Various
      professionals working in the area of CF in Brazil were invited to answer the
      questions devised by the coordinators. We used the PubMed database to search the
      available literature based on keywords, in order to find the best answers to
      these questions. RESUMO A fibrose cistica (FC) e uma doenca genetica autossomica
      recessiva caracterizada pela disfuncao do gene CFTR. Trata-se de uma doenca
      multissistemica que ocorre mais frequentemente em populacoes descendentes de
      caucasianos. Nas ultimas decadas, diversos avancos no diagnostico e tratamento da
      FC mudaram drasticamente o cenario dessa doenca, com aumento expressivo da
      sobrevida e qualidade de vida. Atualmente, o Brasil dispoe de um programa de
      ampla cobertura para a triagem neonatal de FC e centros de referencia
      distribuidos na maior parte desses estados para seguimento dos individuos.
      Antigamente confinada a faixa etaria pediatrica, tem-se observado um aumento de
      pacientes adultos com FC tanto pelo maior numero de diagnosticos de formas
      atipicas, de expressao fenotipica mais leve, assim como pelo aumento da
      expectativa de vida com os novos tratamentos. Entretanto, ainda se observa uma
      grande heterogeneidade no acesso aos metodos diagnosticos e terapeuticos para FC
      entre as diferentes regioes brasileiras. O objetivo dessas diretrizes foi reunir
      as principais evidencias cientificas que norteiam o manejo desses pacientes. Um
      grupo de 18 especialistas em FC elaborou 82 perguntas clinicas relevantes que
      foram divididas em cinco categorias: caracteristicas de um centro de referencia;
      diagnostico; tratamento da doenca respiratoria; tratamento gastrointestinal e
      nutricional; e outros aspectos. Diversos profissionais brasileiros atuantes na
      area da FC foram convidados a responder as perguntas formuladas pelos
      coordenadores. A literatura disponivel foi pesquisada na base de dados PubMed com
      palavras-chave, buscando-se as melhores respostas as perguntas dos autores.

PMID- 28746539
TI  - [Selection of graduate nurses for admission to graduate programs in
      specialization areas].
AB  - The authors analyse the selection process that is being used at the "Escota de
      Enfermagem da Universidade de Sao Paulo", for selection of graduate nurses the
      enrollment in the specialization program on Intensive Care Nursing. They refer
      the objective and the method used at the selection of candidates, as the results
      obtained.

PMID- 28746540
TI  - [Suggestions for the teaching of public health nursing in undergraduate nursing
      programs].
AB  - The authors describe the role of the University in the preparation of human
      resources of nursing and present the bases for planning of the undergraduate
      curriculum, emphasizing the referencial, conceptual, structural and
      methodological frameworks. The principles which should guide nursing education as
      well as the introduction of public health nursing in the curriculum are
      discussed. At least there are formulated questions about the nursing teacher's
      role and the practitioner nursing's role in the actuality.

PMID- 28746541
TI  - [Psychiatry nursing and mental health team members].
AB  - This paper is based on a study on the functions of the nurse, as a member of the
      multiprofessional team, in one Psychiatric Hospital. The populations interviewed
      was composed of 16 nurses, 17 phisicians, 7 social workers, 3 occupational
      therapists and 3 psychologists. The results showed that not even the nurses had a
      clear idea of their functions. The author's conclusions emphasize the need of a
      good undergraduate program on Psychiatric Nursing and on continuing education.

PMID- 28746542
TI  - [The teaching of the nursing prescription].
AB  - The authors refer the orientation given by the instructors of Medical-Surgical
      Nursing to undergraduate students on the nursing prescription, its basic
      principles and the strategies employed.

PMID- 28746543
TI  - [The used of the nursing laboratory by nursing students].
AB  - The authors describle the results of a small survey of the students' training for
      in the Nursing Laboratory of the School of Nursing the improvment of their
      psychomotor hability classroom laboratory. The students answered questions on the
      motivation for the use of the Laboratory, preferences for training alone or with
      classmates and for using the doll or a classmate to simulate the patient, the
      monitoring of a senior student, the bibliography used and the procedures selected
      for training.

PMID- 28746544
TI  - [Rooming-in experience: feelings, needs and expectations referred by living-in
      mothers].
AB  - This work had the finality of searching elements to improve the living-in mothers
      assistance in our hospitals. The population under study included accompanying
      mothers in two different pediatric units. The differences between the two units
      were with respect to room accomodations for mothers and stipulations as to the
      type of disease pathology being treated. The data was collected by way of
      interviews in which a questionnaire of open questions was used. Results showed
      that the rooming-in mothers of the sample felt more discomfort than confort in
      the hospital, due to many different aspects of the hospital situation; the
      principal need of the studied mothers was to be able to give care to their
      children, while others needs related to receiving information about their child's
      condition. The living-in mothers expected to have personal contact with the
      hospital health team while the hospital personnel would be giving assistance to
      the children. Many reasons were given for the varying needs and expectations of
      the rooming-in mothers, showing the individuality of these women and the
      different ways in which a living-in experience affect different mothers.

PMID- 28746545
TI  - [Primary health care in the National Health Service in Sao Paulo and Rio de
      Janeiro: nurse's contribution].

PMID- 28746546
TI  - [Causes of removal from professional duty due to accident of work in a general
      hospital].

PMID- 28746547
TI  - [The role of the nurse in the "Central of the Hospital Infections Committee"].

PMID- 28746548
TI  - Rocinela signata (Isopoda: Aegidae) parasitizing the gills of the spotted
      goatfish Pseudupeneus maculatus (Actinopterygii: Mullidae) in Northeastern
      Brazil.
AB  - Parasitic isopods of fishes usually show wide distribution and low host
      specificity. This study investigated the occurrence of gill parasites in 120
      specimens of spotted goatfish Pseudupeneus maculatus, marine fish of great
      economic importance for fishery community. The fish were captured monthly in the
      Coast of Pernambuco State, Northeast Brazil, between October 2012 and September
      2013. Eleven isopods were found and identified as Rocinela signata. We observed
      lower infections in the gills of P. maculatus (prevalence 8.3%, mean intensity
      1.6+/-0.3 and mean abundance 0.1+/-0.3) when compared to other studies of
      different host fishes from geographically close locations. This parasite has been
      reported from a wide variety of fish species, not only in Brazil, but also in the
      eastern Atlantic and the Pacific oceans. This is the first report of R. signata
      in spotted goatfish.

PMID- 28746549
TI  - Construction and characterization of a recombinant yellow fever virus stably
      expressing Gaussia luciferase.
AB  - Yellow fever is an arthropod-borne viral disease that still poses high public
      health concerns, despite the availability of an effective vaccine. The
      development of recombinant viruses is of utmost importance for several types of
      studies, such as those aimed to dissect virus-host interactions and to search for
      novel antiviral strategies. Moreover, recombinant viruses expressing reporter
      genes may greatly facilitate these studies. Here, we report the construction of a
      recombinant yellow fever virus (YFV) expressing Gaussia luciferase (GLuc) (YFV
      GLuc). We show, through RT-PCR, sequencing and measurement of GLuc activity, that
      stability of the heterologous gene was maintained after six passages.
      Furthermore, a direct association between GLuc expression and viral replication
      was observed (r2=0.9967), indicating that measurement of GLuc activity may be
      used to assess viral replication in different applications. In addition, we
      evaluated the use of the recombinant virus in an antiviral assay with recombinant
      human alfa-2b interferon. A 60% inhibition of GLuc expression was observed in
      cells infected with YFV-GLuc and incubated with IFN alfa-2b. Previously tested on
      YFV inhibition by plaque assays indicated a similar fold-decrease in viral
      replication. These results are valuable as they show the stability of YFV-GLuc
      and one of several possible applications of this construct.

PMID- 28746550
TI  - Melipona mondury produces a geopropolis with antioxidant, antibacterial and
      antiproliferative activities.
AB  - Geopropolis is a special type of propolis produced by stingless bees. Several
      pharmacological properties have been described for different types of
      geopropolis, but there have been no previous studies of the geopropolis from
      Melipona mondury. In this study, we investigated the antioxidant, antibacterial,
      and antiproliferative activities of M. mondury geopropolis, and determined its
      chemical profile. The antioxidant activity was determined using in vitro ABTS.+,
      .DPPH, and beta-carotene/linoleic acid co-oxidation methods. The antibacterial
      activity was determined using a microdilution method with Pseudomonas aeruginosa,
      Staphylococcus aureus, and methicillin-resistant S. aureus. The antiproliferative
      effect was determined in tumor cell lines using the Alamar Blue assay. The
      chemical profile was obtained using UHPLC-MS and UHPLC-MS/MS. The butanolic
      fraction had the highest concentration of phenolic compounds and more potent
      antioxidant properties in all assays. This fraction also had bacteriostatic and
      bactericidal effects against all bacterial strains at low concentrations,
      especially S. aureus. The hexane fraction had the highest antiproliferative
      potential, with IC50 values ranging from 24.2 to 46.6 ug/mL in HL-60 (human
      promyelocytic leukemia cell) and K562 (human chronic myelocytic leukemia cell),
      respectively. Preliminary chemical analysis indicates the presence of terpenes
      and gallic acid in the geopropolis. Our results indicate the therapeutic
      potential of geopropolis from M. mondury against inflammatory, oxidative,
      infectious, and neoplastic diseases.

PMID- 28746551
TI  - Copper II - polar amino acid complexes: toxicity to bacteria and larvae of Aedes
      aegypti.
AB  - Control strategies using insecticides are sometimes ineffective due to the
      resistance of the insect vectors.In this scenario new products must be proposed
      for the control of insect vectors.The complexes L-aspartate Cu (II) and L
      glutamate-Cu (II) complexes were synthesized and characterized by elemental
      analysis, visible ultraviolet, infrared spectroscopy and potentiometric
      titration. The toxicity of these complexes was analyzed in Aedes aegypti
      (Diptera: Culicidae) larvae and Gram-negative and Gram-positive bacteria. The
      interaction between the ligands and the amino acid balance and the distribution
      of the species as a function of pH were discussed. The lethal concentration
      median (LC50) for Ae. aegypti larvae were: L-glutamic acid-Cu (II) - 53.401 mg L
      1 and L-aspartate-Cu (II) - 108.647 mg L-1. The minimum inhibitory concentration
      (MIC) required for Staphylococcus aureus and Escherichia coli was: L-glutamate-Cu
      (II) 500-2000 mg L-1 and L-aspartate-Cu (II) 1000-2000 mg L-1. The concentrations
      demonstrated toxicity that evidence the potential of the complexes as bactericide
      and insecticide. Metal complexes formed by amino acids and transition metals are
      advantageous because of low environmental toxicity, biodegradability and low
      production cost.

PMID- 28746552
TI  - Growth of the silverside Atherinella brasiliensis in a subtropical estuary with
      some insights concerning the weight-length relationship.
AB  - Specimens of Brazilian silverside (Atherinella brasiliensis, n=9672) with a
      length range of 1.5 to 14.2 cm were captured in the intertidal areas of the
      Estuarine Complex of Paranagua, Brazil, between August 2010 and July 2011. The
      species' weight-length relationship was represented by the equation W=0.00533
      L3.136 with a slightly positive allometry (b>3) and could be divided into two
      growth stanzas: W = W1 + W2; Stanza 1: W1= SW. (0.005239 L3.152); Stanza 2: W2=
      (1 - SW). (0.000699 L3.913); Switch-Function: SW = [1 + e1.204 (L - 11.66)]-1.
      The breakpoint between the first and second stanza (11.66 cm) matches published
      values for the estimated size at first maturity of adult females. Frequency
      distributions indicate that the species is present in the shallow areas of the
      Estuarine Complex of Paranagua during all phases of its ontogenetic development,
      with the recruitment of juveniles taking place between October and November.
      Modal displacement was monitored throughout 12 months. The von Bertalanffy growth
      model and longevity was estimated as follow: asymptotic length (Linfinity) of
      17.5 cm, growth coefficient (K) of 0.89 (year-1) and longevity (A95) of 3.33
      years. We present some considerations with regard to the general methodology for
      adjusting weight-length relationships.

PMID- 28746553
TI  - Gill parasites of fish from two estuaries in northeastern Brazil: new hosts and
      geographical records.
AB  - Parasites are important components of communities and constitute great part of
      the biological diversity found in ecosystems, providing valuable information
      about their hosts and the environment in which they live. However, despite its
      importance, parasitic diversity is still not well known in some regions of
      Brazil, especially with respect to fish parasites in the Northeast Region. The
      present study aims to perform the survey of gill parasites of fish from two
      tropical estuaries located in northeastern Brazil: Paraiba and Mamanguape rivers.
      Two collections were made in each estuary, one during the dry period (November /
      2013) and the other during the rainy season (July / 2014). The fish were caught
      using a beach seine net, dragged along the main channel margin. After the
      identification, biometry and necropsy of the fish, their parasites were
      collected, stored and identified. For each species of parasite, the values of
      prevalence, mean intensity and mean abundance were calculated. Of the 882
      examined fish, belonging to four species, 145 were parasitized by at least one
      species of parasite. In total, 18 taxa of parasites of the groups Monogenea,
      Digenea, Nematoda, Copepoda and Isopoda were recorded, being the copepod
      Acusicola brasiliensis the most abundant species of parasite.

PMID- 28746554
TI  - Phenological characterization and temperature requirements of Annona squamosa L.
      in the Brazilian semiarid region.
AB  - The phenological growth stages of various species of monocotyledonous and
      dicotyledonous plants can be uniformly coded using the Biologische Bundesanstalt,
      Bundessortenamt, und Chemische Industrie (BBCH) scale. The aim of the present
      study was to determine the duration of different phenological stages and the
      temperature requirements of the sugar-apple, Annona squamosa, during two crop
      cycles in the semiarid region of Brazil. Phenological stages were divided into
      eight of ten possible principal stages: (0) bud development, (1) leaf
      development, (3) shoot/branch development, (5) inflorescence emergence, (6)
      flowering, (7) fruit development, (8) fruit maturity and (9) senescence and the
      beginning of dormancy. The phenological cycle of the sugar-apple from having
      closed leaf buds to the fruit ripening stage lasted 149 and 164 days with
      temperature requirements of 1684.5 and 1786.7 degree days (DD) for the first and
      second crop cycles, respectively. The results provided important information that
      will inform the correct timing for crop management practices.

PMID- 28746555
TI  - The color of pain: racial iniquities in prenatal care and childbirth in Brazil.
AB  - Few studies on the influence of race/color on pregnancy and birthcare experiences
      have been carried out in Brazil. Additionally, none of the existing studies are
      of national scope. This study sought to evaluate inequities in prenatal and
      childbirth care according to race/color using propensity score matching. The data
      comes from the study Birth in Brazil: National Survey into Labor and Birth, a
      national population study comprised of interviews and revisions of medical
      records that included 23,894 women in 2011/2012. We used logistic regressions to
      estimate odds ratios (OR) and respective 95% confidence intervals (95%CI) of
      race/color associated with the outcomes were analyzed. When compared with white
      skinned women, black-skinned women were more likely to have inadequate prenatal
      care (OR = 1.6; 95%CI: 1.4-1.9), to not be linked to a maternity hospital for
      childbirth (OR = 1.2 95%CI: 1.1-1.4), to be without a companion (OR = 1.7; 95%CI:
      1.4-2.0), to seek more than one hospital for childbirth (OR =1.3; 95%CI: 1.2
      1.5), and less likely to receive local anesthesia for an episiotomy (OR = 1.5;
      95%CI: 1.1-2.1). Brown-skinned women were also more likely to have inadequate
      prenatal care (OR = 1.2; 95%CI: 1.1-1.4) and to lack a companion (OR = 1.4;
      95%CI: 1.3-1.6) when compared with white-skinned women. We identified racial
      disparities in care during pregnancy and childbirth, which displayed a gradient
      going from worst to best care provided to black, brown and white-skinned women.

PMID- 28746556
TI  - Potential intravenous drug interactions in intensive care.
AB  - OBJECTIVE: To analyze potential intravenous drug interactions, and their level of
      severity associated with the administration of these drugs based on the
      prescriptions of an intensive care unit. METHOD: Quantitative study, with
      aretrospective exploratory design, and descriptive statistical analysis of the
      ICU prescriptions of a teaching hospital from March to June 2014. RESULTS: The
      sample consisted of 319 prescriptions and subsamples of 50 prescriptions. The
      mean number of drugs per patient was 9.3 records, and a higher probability of
      drug interaction inherent to polypharmacy was evidenced. The study identified
      severe drug interactions, such as concomitant administration of Tramadol with
      selective serotonin reuptake inhibitor drugs (e.g., Metoclopramide and
      Fluconazole), increasing the risk of seizures due to their epileptogenic actions,
      as well as the simultaneous use of Ranitidine-Fentanyl(r), which can lead to
      respiratory depression. CONCLUSION: A previous mapping of prescriptions enables
      the characterization of the drug therapy, contributing to prevent potential drug
      interactions and their clinical consequences. OBJETIVO: Analisar as potenciais
      interacoes medicamentosas intravenosas e seu grau de severidade associadas a
      administracao desses medicamentos a partir das prescricoes do Centro de Terapia
      Intensiva. METODO: Estudo quantitativo, tipologia retrospectiva exploratoria, com
      analise estatistica descritiva das prescricoes medicamentosas do Centro de
      Terapia Intensiva de um Hospital Universitario, no periodo de marco-junho/2014.
      RESULTADOS: A amostra foi composta de 319 prescricoes e subamostras de 50
      prescricoes. Constatou-se que a media de medicamentos por paciente foi de 9,3
      registros, e evidenciou-se maior probabilidade para ocorrencia de interacao
      medicamentosa inerente a polifarmacia. O estudo identificou interacoes
      medicamentosas graves, como a administracao concomitante de Tramadol com
      medicamentos inibidores seletivos da recaptacao da serotonina, (exemplo:
      Metoclopramida e Fluconazol), aumentando o risco de convulsoes devido as suas
      acoes epileptogenicas, alem do uso simultaneo de Ranitidina-Fentanil(r), que pode
      ocasionar depressao respiratoria. CONCLUSAO: O mapeamento previo das prescricoes
      possibilita a caracterizacao da terapeutica medicamentosa, contribuindo para
      obstar as potenciais interacoes medicamentosas e suas consequencias clinicas.

PMID- 28746557
TI  - Occupational Burnout Syndrome in the nursing context: an integrative literature
      review.
AB  - OBJECTIVE: To characterize the scientific production on Burnout Syndrome in the
      Nursingcontext, systematizing the location where the studies were carried out,
      the related constructs, the employed methods and their main results. METHOD: An
      integrative review of the literature with a bibliometric approach of articles
      published in Portuguese, Spanish and English between 2005 and 2016. RESULTS: 106
      articles wereincluded. Mostinvolvedprevalence, and were descriptive, quantitative
      studies performed in hospitals.The Southeastern and Southern regions of Brazil
      had the largest number of publications, and stress was the construct most related
      to burnout.Most of the studies used the Maslach Burnout Inventory to investigate
      the presence of the syndrome. CONCLUSION: New case-control and cohort studies
      should be carried out.Qualitative-exploratory studies are necessary to better
      understand Burnout Syndrome among nursing professionals usingfocus groups or
      interviews, as well as comparative causal studies, with the purpose of exploring
      the syndrome'smanifestations. OBJETIVO: Caracterizar a producao cientifica sobre
      a Sindrome do Esgotamento Profissionalno contexto da enfermagem, sistematizando
      os locais onde as pesquisas foram realizadas, os construtos relacionados, os
      metodos empregados e seus principais resultados. METODO: Revisao integrativa da
      literatura, com abordagem bibliometrica, em artigos na lingua portuguesa,
      espanhola e inglesa publicados entre 2005 e 2016. RESULTADOS: Foram selecionados
      106 artigos.A maioria estudos de prevalencia, descritivos, quantitativos e
      realizados em hospitais. Nas regioes Sudeste e Sul do Brasil encontram-se o maior
      numero de publicacoes, sendo o estresse o construto mais relacionado com o
      esgotamento profissional. A maior parte dos estudos utilizou o Maslach Burnout
      Inventory como meio de averiguacao da presenca da sindrome. CONCLUSAO: Novos
      estudos de caso controle e coorte devem ser realizados. Pesquisas de cunho
      qualitativo-exploratorio sao necessarias para poder compreender melhor a Sindrome
      do Esgotamento Profissionalentre os profissionais de enfermagem com grupos focais
      ou entrevistas, como tambem pesquisas causais comparativas, com o intuito de
      explorar as manifestacoes da sindrome.

PMID- 28746558
TI  - Effects of prayer on the vital signs of patients with chronic kidney disease:
      randomized controlled trial.
AB  - OBJECTIVE: To assess the effect of prayer on blood pressure, heart rate and
      respiratory rate in patients with chronic kidney disease and learn their
      perception of the intervention. METHOD: A randomized controlledtrial, double
      blind with a sample of volunteers, randomized into an intervention group (n=42)
      and a control group (n=37). Questionnaires addressing socio-demographic, clinical
      and spiritual characteristics and the Duke University Religious Index were
      applied. Blood pressure, heart rate and respiratory rate were measured. The
      prayer was conducted at three different moments on alternating weeks. The
      qualitative data were organized and analyzed through Thematic Analysis. RESULTS:
      The sample consisted of 95 randomized volunteers. In the intra-group analysis, a
      statistically significant reduction (P<0001) of blood pressure, heart rate and
      respiratory rate was observed in all evaluations of the people who were prayed
      for. The qualitative analysis resulted in the themes Prayer in a "Place of
      Suffering" and Positive Evaluation and in the sub-themes Relief from Suffering,
      Hope for Improvement, and Coping with Hemodialysis. CONCLUSIONPrayer reduced
      blood pressure, heart rate and respiratory rate in patients who suffer from
      chronic kidney disease, and the volunteers' evaluation of the intervention was
      positive.BrazilianClinicalTrials Registry: RBR-2zv39y. OBJETIVO: Avaliar o efeito
      da prece sobre a pressao arterial, a frequencia cardiaca e respiratoria em
      paciente com insuficiencia renal cronica e conhecer sua percepcao a respeito da
      intervencao. METODO: Ensaio clinico controlado, randomizado, duplo cego com uma
      amostra de voluntarios, randomizados em grupo intervencao (n=42) e grupo controle
      (n=37). Foram aplicados, por meio de entrevista, um questionario de
      caracteristicas sociodemograficas, clinicas e espirituais e o Indice de
      Religiosidade da Universidade de Duke, alem da mensuracao da pressao arterial,
      frequencia cardiaca e respiratoria. A prece foi ministrada em tres momentos
      diferentes, durantes semanas alternadas. Os dados qualitativos foram organizados
      e analisados por meio da Analise Tematica. RESULTADOS: A amostra totalizou 95
      voluntarios randomizados.Na analiseintragruposfoi observada uma reducao
      estatisticamente significativa (P<0001) dos valores de pressao arterial,
      frequencia cardiaca e respiratoria em todas as analises das pessoas que receberam
      a prece. Aanalise qualitativa resultou nos temasA Prece em um "Lugar de
      Sofrimento" e Avaliacao Positiva e nos subtemas Alivio do Sofrimento, Esperanca
      de Superacao, Enfrentamento do Tratamento Hemodialitico. CONCLUSAO: A prece
      reduziu os valores da pressao arterial, frequencia cardiaca e respiratoria de
      pacientes com insuficiencia renal cronica e a avaliacao dos voluntarios em
      relacao a intervencao foi positiva. Registro Brasileiro de Ensaios Clinicos: RBR
      2zv39y.

PMID- 28746559
TI  - Factors associated with the risk of falls in hospitalized adult patients.
AB  - OBJECTIVE: Analyzing factors related to the risk of falls in hospitalized adult
      patients. METHOD: A cross-sectional, analytical and quantitative study, developed
      in Clinical and Surgical Hospitalization Units from June to August 2015. Data
      collection instruments were sociodemographic and clinical forms, and the Morse
      Scale. Data were obtained with the patients and from medical records. Absolute
      and relative frequencies were used in the univariate statistical analysis, and
      chi-square test in the bivariate analysis. RESULTS: 612 patients participated in
      the study. An association (p<0.001) was found between the high risk of falls and
      clinical neurological hospitalization, surgical trauma (hospitalization) and
      comorbidities such as diabetes mellitus, systemic arterial hypertension, visual
      impairment, vertigo and fear of falling. CONCLUSION: An association between the
      risk of falls was found due to hospitalization, comorbidities and intrinsic
      factors. Regarding extrinsic factors, an association between mats/carpets and
      risk of falls was found. No association between the risk of falls with other
      extrinsic factors was found. OBJETIVO: Analisar os fatores relacionados ao risco
      de quedas em pacientes adultos internados em um hospital. METODO: Estudo
      transversal, analitico e quantitativo, desenvolvido em Unidades de Internacao
      Clinica e Cirurgica, no periodo de junho a agosto 2015. Os instrumentos de coleta
      de dados foram formularios sociodemografico, clinico e Escala de Morse. Os dados
      foram obtidos com os pacientes e nos prontuarios. Na analise estatistica
      univariada utilizou-se de frequencia absoluta e relativa, e na bivariada utilizou
      se do teste de qui-quadrado. RESULTADOS: Participaram do estudo 612 pacientes.
      Foi encontrada associacao (p<0,001) entre o elevado risco de queda e a internacao
      clinica neurologica, a cirurgica traumatologica e comorbidades como diabetes
      mellitus, hipertensao arterial sistemica, dificuldade visual, vertigens e medo de
      cair. CONCLUSAO: Existe associacao entre o risco de quedas com motivo de
      internacao, comorbidades e fatores intrinsecos. Em relacao aos fatores
      extrinsecos, foi encontrada associacao entre tapetes e risco de quedas. Nao houve
      associacao entre o risco de quedas com outros fatores extrinsecos.

PMID- 28746560
TI  - Developing and validating the Perioperative Thirst Discomfort Scale.
AB  - OBJECTIVE: Developing and validating a scale to assess perioperative thirst
      discomfort. METHOD: A methodological research conducted in 2014 and 2015 at the
      surgical center of a public hospital in the north of Parana, Brazil. The scale
      was developed after literature review, followed by face and content validation,
      and reliability assessment through its internal consistency and inter-observer
      equivalence. RESULTS: Seven items make up the scale: dry mouth; dry lips; thick
      tongue; thick saliva; dry throat, bad taste and desire to drink water. The
      content validity index for attributes and items was 0.98, and the reliability
      index was 1 for the scale attributes and items. Internal consistency assessed by
      Cronbach's alpha was 0.91 and inter-rater equivalence was 1, as measured by
      weighted kappa coefficient. CONCLUSION: ThePerioperative Thirst Discomfort
      Scaleshowed high content and reliability indexes. OBJETIVO: Elaborar e validar
      uma escala para avaliacao do desconforto da sede perioperatoria. METODO: Pesquisa
      metodologica realizada em 2014 e 2015, no centro cirurgico de um hospital publico
      do norte do Parana. A escala foi elaborada apos revisao bibliografica, seguida de
      validacao aparente e de conteudo e avaliacao da fidedignidade atraves de sua
      consistencia interna e da equivalencia inter observadores. RESULTADOS: Sete itens
      compuseram a escala: boca seca; labios ressecados; lingua grossa; saliva grossa;
      garganta seca; gosto ruim e vontade de beber agua. O indice de validade de
      conteudo para atributos e itens foi de 0,98, e o indice de fidedignidade foi de 1
      para os atributos e itens da escala. A consistencia interna avaliada pelo alfa de
      Cronbach foi de 0,91, e a equivalencia interobservadores foi de 1, medida pelo
      coeficiente de kappa ponderado. CONCLUSAO: A escala de desconforto da sede
      perioperatoriademonstrou altos indices de validade de conteudo e fidedignidade.

PMID- 28746561
TI  - ?

PMID- 28746562
TI  - [Nursing theories - International conference].

PMID- 28746563
TI  - [Mothers in the pediatric ward: an analysis of the nurse's behavior].
AB  - The author noticed an indifferent attitude on the part of nurses in the presence
      of mothers in the pediatric ward and reflects upon what she understands to be
      possible reasons for this behavior.

PMID- 28746564
TI  - [Body composition of feed-restricted female rats, at the first estrus].
AB  - At first estrus the feed-restricted rats were older and, proportionally to the
      age, leaner than the well fed animals. They had attained a greater proportion of
      protein and lesser proportion of water and fat; however the animals of the two
      restricted diet groups and the well fed group had the same weight. First estrus
      was simultaneous with vaginal opening in 90% of the well fed animals, in 20% of
      the group I and in 0% of the group II.

PMID- 28746565
TI  - [Theoretical frame of reference].
AB  - The author approaches the theoretical knowledge in nursing, bringing into focus
      some main works published on the theme and makes comments about conceptual
      framework and theories as a frame of reference for professional action.

PMID- 28746566
TI  - [Nursing behavior during the admission of a child to the hospital].
AB  - A qualitative analysis is made of the nursing procedure of admitting a child to a
      governmental general hospital, with emphasis upon to the role of the nurse. The
      purpose of the analysis is to obtain data which could facilitate the
      understanding of the nurse's involvement in this procedure. The data will later
      be used in a participative research project which will be made with the nursing
      team in a pediatric ward.

PMID- 28746567
TI  - [Relactation: bibliografical review].
AB  - In non-industrialized societies, for instance, Bantu and Zulu, relactation is an
      important oportunity of survival for the orphan new-born. In ocidental urban
      societies relactation has been made by multidisciplinary staffs, with the aim of
      promoting good mother-son interation and to flight desnutrition in childhood.
      Cultural influence is emphasized in the natural nursing process and in
      relactation.

PMID- 28746568
TI  - [Preparation to motherhood by the group structure].
AB  - The authors, who are undergraduate nursing students, describe a method they have
      employed to prepare pregnant women and "pregnant comples" for delivery. This
      method, which includes individual and group sessions, is centered on the
      patients' needs and emphasizes the importance of understanding the anatomical,
      physiological and psychological changes occurring in pregnancy.

PMID- 28746569
TI  - ?

PMID- 28746570
TI  - Brazilian guidelines for the clinical management of paracoccidioidomycosis.
AB  - Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America
      that is associated with rural environments and agricultural activities. However,
      the incidence and prevalence of paracoccidiodomycosis is underestimated because
      of the lack of compulsory notification. If paracoccidiodomycosis is not diagnosed
      and treated early and adequately, the endemic fungal infection could result in
      serious sequelae. While the Paracoccidioides brasiliensis ( P. brasiliensis )
      complex has been known to be the causal agent of paracoccidiodomycosis, a new
      species, Paracoccidioides lutzii ( P. lutzii ), has been reported in Rondonia,
      where the disease has reached epidemic levels, and in the Central West and Para.
      Accurate diagnoses and availability of antigens that are reactive with the
      patients' sera remain significant challenges. Therefore, the present guidelines
      aims to update the first Brazilian consensus on paracoccidioidomycosis by
      providing evidence-based recommendations for bedside patient management. This
      consensus summarizes etiological, ecoepidemiological, molecular epidemiological,
      and immunopathological data, with emphasis on clinical, microbiological, and
      serological diagnosis and management of clinical forms and sequelae, as well as
      in patients with comorbidities and immunosuppression. The consensus also includes
      discussion of outpatient treatments, severe disease forms, disease prevalence
      among special populations and resource-poor settings, a brief review of
      prevention and control measures, current challenges and recommendations.

PMID- 28746571
TI  - Insufficient free-time physical activity and occupational factors in Brazilian
      public school teachers.
AB  - OBJECTIVE: To evaluate if perceived occupational factors are associated with
      insufficient free-time physical activity in Brazilian public school teachers.
      METHODS: The relationship between insufficient physical activity (< 150
      minutes/week) and variables related to work was analyzed in 978 elementary and
      high school teachers calculating the prevalence ratio (PR) and 95% confidence
      interval (95%CI) in Poisson regression models, adjusted for sociodemographic and
      health variables. RESULTS: The prevalence of insufficient physical activity was
      71.9%, and this condition was associated independently with the perception of bad
      or regular balance between personal and professional life (PR = 1.09; 95%CI 1.01
      1.18), perception that standing time affects the work (PR = 1.16; 95%CI 1.01
      1.34), low or very low perception of current ability for the physical
      requirements of work (PR = 1.21; 95%CI 1.08-1.35), and temporary employment
      contract (PR = 1.13; 95%CI 1.03-1.25). The teaching of physical education was
      associated with lower prevalence of insufficient physical activity (PR = 0.78;
      95%CI 0.64-0.95). CONCLUSIONS: The perception of adverse working conditions is
      associated with increased prevalence of insufficient physical activity in
      teachers and should be considered for the promotion of physical activity in this
      population. OBJETIVO: Analisar se fatores ocupacionais percebidos estao
      associados a atividade fisica insuficiente no tempo livre em professores de
      escolas publicas. METODOS: A relacao entre atividade fisica insuficiente (< 150
      minutos/semana) e variaveis relacionadas ao trabalho foi analisada em 978
      professores do ensino fundamental e medio mediante o calculo da razao de
      prevalencia (RP) e intervalo de confianca de 95% (IC95%) em modelos de regressao
      de Poisson, ajustados por variaveis sociodemograficas e de saude. RESULTADOS: A
      prevalencia de atividade fisica insuficiente foi de 71,9%, e essa condicao
      associou-se de maneira independente com percepcao de equilibrio entre vida
      pessoal e profissional ruim ou regular (RP = 1,09; IC95% 1,01-1,18), percepcao de
      que o tempo de permanencia em pe afeta o trabalho (RP = 1,16; IC95% 1,01-1,34),
      percepcao de capacidade atual para as exigencias fisicas do trabalho baixa ou
      muito baixa (RP = 1,21; IC95% 1,08-1,35) e contrato de trabalho temporario (RP =
      1,13; IC95% 1,03-1,25). Ministrar disciplina de educacao fisica associou-se com
      menor prevalencia de atividade fisica insuficiente (RP = 0,78; IC95% 0,64-0,95).
      CONCLUSOES: A percepcao de condicoes de trabalho negativas associa-se a maior
      prevalencia de atividade fisica insuficiente em professores e devem ser
      consideradas para a promocao de atividade fisica nessa populacao.

PMID- 28746572
TI  - Effect of the exercise of walkers performed in public squares with spontaneous or
      prescribed intensity on post-exercise hypotension.
AB  - OBJECTIVE: To quantify the intensity adopted by walkers in public squares and
      check the occurrence and magnitude of post-exercise hypotension in the
      spontaneously adopted intensity and in a prescribed intensity. METHODS: In 98
      volunteers (38 of them being hypertensive), walkers in public squares of the city
      of Joao Pessoa, State of Paraiba, Brazil, we have identified the intensity of a
      usual training monitored by heart rate and we have investigated the occurrence
      and magnitude of post-exercise hypotension. Subsequently, participants were
      instructed to walk with moderate intensity. Blood pressure was measured after
      rest and during post-exercise recovery. RESULTS: Of the total participants, 41%
      of the hypertensive and 36% of the normotensive individuals walked with light
      intensity. With the prescription, intensity increased to 55% and 52%, for the
      hypertensive and normotensive individuals, respectively. In the usual and
      prescribed intensity, the hypertensive individuals had post-exercise hypotension
      of -3.7+/-11.6 mmHg and -4.72+/-12.8 mmHg, respectively. There was no correlation
      between post-exercise hypotension and the initial systolic component of the
      hypertensive individuals (r2 = 0.2; p < 0.002). CONCLUSIONS: Walkers in public
      squares choose light intensity for walking. When they exercise with the
      prescribed intensity, they increase the intensity, but the magnitude of the PEH
      is not increase with this guidance. OBJETIVO: Quantificar a intensidade adotada
      por caminhantes em pracas publicas e verificar a ocorrencia e a magnitude da
      hipotensao pos-exercicio na intensidade espontaneamente adotada e em uma
      intensidade prescrita. METODOS: Em 98 voluntarios (38 hipertensos), caminhantes
      em pracas publicas da cidade de Joao Pessoa, PB, identificamos a intensidade de
      um treino habitual monitorada por meio da frequencia cardiaca e averiguamos a
      ocorrencia e magnitude de hipotensao pos-exercicio. Posteriormente, os
      participantes foram instruidos a caminhar com intensidade moderada. A pressao
      arterial foi aferida apos o repouso e durante a recuperacao pos-exercicio.
      RESULTADOS: Do total de participantes, 41% dos hipertensos e 36% dos normotensos
      caminhavam com intensidade leve. Com a prescricao, a intensidade aumentou para
      55% e 52%, para hipertensos e normotensos. Na intensidade habitual e prescrita,
      os hipertensos obtiveram hipotensao pos-exercicio de -3,7+/-11,6 mmHg e -4,72+/
      12,8 mmHg. Houve correlacao entre hipotensao pos-exercicio e o componente
      sistolico inicial dos hipertensos (r2 = 0,2; p < 0,002). CONCLUSOES: Caminhantes
      em pracas publicas selecionam intensidade leve para realizacao de caminhada.
      Quando realizam exercicio com intensidade prescrita, aumentam discretamente a
      intensidade, mas nao obtem aumento da magnitude da HPE com esta orientacao.

PMID- 28746573
TI  - Quality of life, socioeconomic and clinical factors, and physical exercise in
      persons living with HIV/AIDS.
AB  - OBJECTIVE: To analyze whether socioeconomic and clinical aspects and the aspects
      of healthy life habits are associated with the quality of life of persons living
      with HIV/AIDS. METHODS: This is a cross-sectional exploratory quantitative
      research, with 227 persons living with HIV/AIDS, treated at two hospitals of
      reference between April 2012 and June 2014. We used structured questionnaires to
      assess socioeconomic aspects (gender, age, education level, marital status, race,
      socioeconomic status, dependents on family income, employment relationship),
      clinical parameters (time of disease diagnosis, use and time of medication, CD4 T
      cell count, and viral load), and practice of physical exercise. To assess quality
      of life, we used the Quality of Life questionnaire (HAT-QoL). For
      characterization of the socioeconomic and clinical data and domains of quality of
      life, we conducted a descriptive analysis (simple frequency, averages, and
      standard deviations). We applied linear regression, following a hierarchical
      model for each domain of quality of life. RESULTS: The domains that presented
      lower averages for quality of life were financial concern, concern with
      confidentiality, general function, and satisfaction with life. We found
      associations with the variables of socioeconomic status and physical exercise,
      therapy, and physical exercise for the last two domains, consecutively.
      CONCLUSIONS: The quality of life of persons living with HIV/AIDS shows losses,
      especially in the financial and confidentiality areas, followed by general
      function of the body and satisfaction with life, in which socioeconomic and
      clinical aspects and healthy living habits, such as the practice of physical
      exercise, are determining factors for this reality. OBJETIVO: Analisar se
      aspectos socioeconomicos, clinicos e de habitos de vida saudavel estao associados
      a qualidade de vida em pessoas vivendo com HIV/aids. METODOS: Pesquisa
      quantitativa exploratoria de corte transversal, com 227 pessoas vivendo com
      HIV/aids, atendidos em dois hospitais de referencia entre os periodos de abril
      2012 a junho de 2014. Foram utilizados questionarios estruturados para avaliar
      aspectos socioeconomicos (sexo, idade, escolaridade, estado civil, cor de pele,
      status socioeconomico, dependentes da renda familiar, vinculo empregaticio),
      parametros clinicos (tempo de diagnostico da doenca, uso e tempo de medicacao,
      contagem de celulas TCD4 e carga viral) e pratica de exercicio fisico. Para
      avaliar qualidade de vida, utilizou-se o questionario Quality of Life (HAT-QoL).
      Para caracterizacao dos dados socioeconomicos, clinicos e dominios da qualidade
      de vida, conduzimos analise descritiva (frequencia simples, medias e desvios
      padrao). Aplicamos regressao linear, seguindo um modelo hierarquico para cada
      dominio da qualidade de vida. RESULTADOS: Os dominios que apresentaram menores
      medias para a qualidade de vida foram preocupacao financeira, preocupacao com
      sigilo, funcao geral e satisfacao com a vida. Foram encontradas associacoes com
      as variaveis status socioeconomico e exercicio fisico; terapia; e exercicio
      fisico para os dois ultimos dominios, consecutivamente. CONCLUSOES: A qualidade
      de vida de pessoas vivendo com HIV/aids apresentam prejuizos, principalmente nas
      questoes financeiras e de sigilo, seguidos da funcao geral do corpo e satisfacoes
      com a vida, em que os aspectos socioeconomicos, clinicos e habitos de vida
      saudavel, como a pratica de exercicio fisico, sao fatores determinantes para essa
      realidade.

PMID- 28746574
TI  - Institutional violence and quality of service in obstetrics are associated with
      postpartum depression.
AB  - OBJECTIVE: To investigate the association between institutional violence in
      obstetrics and postpartum depression (PP depression) and the potential effect of
      race, age, and educational level in this outcome. METHODS: This is a cross
      sectional study about the health care conditions for the maternal and child
      population of the Federal District, Brazil, carried out in 2011. The study has
      used a probabilistic sample of 432 women, whose children were aged up to three
      months, stratified by clusters. Indicators of institutional violence and
      demographic characteristics have been used in a logistic regression model to
      estimate the probability of occurrence of postpartum depression. RESULTS: The
      model has identified a high prevalence of postpartum depression, being it higher
      among non-white women and adolescent females, besides having a strong positive
      association between the several indicators of obstetric violence and postpartum
      depression. Positive interactions on a multiplicative scale have also been
      observed between: violence by negligence by health care professionals and race
      and age; physical violence from health care professionals and age; and, verbal
      violence from health care professionals and race. CONCLUSIONS: The indicators
      adopted to reflect institutional violence in obstetric care are positively
      associated with postpartum depression, which calls for a reflection on the need
      to make the health care protocols adequate to the precepts of the Brazilian
      humanization of childbirth care policies and changes in the obstetric care model.

PMID- 28746575
TI  - Social determinants of leprosy in a hyperendemic State in North Brazil.
AB  - OBJECTIVE: To identify the socioeconomic, demographic, operational, and health
      service-related factors associated with the occurrence of leprosy in a
      hyperendemic State in North Brazil. METHODS: This is an ecological study based on
      secondary data from the Sistema de Informacoes de Agravos de Notificacao in
      municipalities of the State of Tocantins from 2001 to 2012. Units of analysis
      were the 139 municipalities of the State. Negative binomial log linear regression
      models were used to estimate incidence rate ratios. RESULTS: In bivariate
      analysis, the incidence rate ratios were significantly higher for municipalities
      with higher income ratio of the poorest 20.0% (1.47; 95%CI 1.19-1.81) and better
      Municipal Human Development Index (1.53; 95%CI 1.14-2.06). In multivariate
      analysis, the incidence rate ratios were significantly higher in municipalities
      with higher proportion of immigrants (1.31; 95%CI 1.11-1.55) and higher
      proportion of households with waste collection (1.37; 95%CI 1.11-1.69). There was
      a significant reduction in the incidence rate ratio with increased coverage of
      the Bolsa Familia Program (0.98; 95%CI 0.96-0.99). CONCLUSIONS: Control programs
      need to focus on activities in municipalities of greater social vulnerability
      with intersectoral investment for the improvement of the living conditions of the
      population. OBJETIVO: Identificar fatores socioeconomicos, demograficos,
      operacionais e de servicos de saude associados a ocorrencia da hanseniase em um
      estado hiperendemico do norte do Brasil. METODOS: Estudo ecologico com dados
      secundarios do Sistema de Informacoes de Agravos de Notificacao em municipios do
      estado do Tocantins de 2001 a 2012. As unidades de analise foram os 139
      municipios do estado. Modelos de regressao log linear binomial negativa foram
      utilizados para estimar as razoes de taxas de incidencia. RESULTADOS: Na analise
      bivariada, a razao de taxa de incidencia foi significativamente maior para os
      municipios com maior razao de renda dos 20,0% mais pobres (1,47; IC95% 1,19-1,81)
      e melhor Indice de Desenvolvimento Humano Municipal (1,53; IC95% 1,14-2,06). Na
      multipla, a razao de taxa de incidencia foi significativamente superior em
      municipios com maior concentracao de imigrantes (1,31; IC95% 1,11-1,55) e
      proporcao de domicilios com coleta de lixo (1,37; IC95% 1,11-1,69). Houve reducao
      significativa da razao de taxa de incidencia com o aumento da cobertura do
      programa bolsa familia (0,98; IC95% 0,96-0,99). CONCLUSOES: Os programas de
      controle precisam focar as atividades em municipios de maior vulnerabilidade
      social com investimentos intersetoriais para a melhoria das condicoes de vida da
      populacao.

PMID- 28746577
TI  - ?

PMID- 28746576
TI  - Quality of cervical cancer screening in Brazil: external assessment of the PMAQ.
AB  - OBJECTIVE: To examine whether demographic and socioeconomic variables and the
      variables of the organization of services are associated with the quality of
      cervical cancer screening. METHODS: This is a survey carried out in the health
      services of the five Brazilian regions in 2012. The sample consisted of users of
      basic health units participating in the Program for Improving Access and Quality
      of the Primary Care. The independent variables analyzed were: socioeconomic
      characteristics (municipal context), demographic characteristics (user profile),
      and two domains related to the organization of basic services (work structure and
      process). The low quality of the screening was assessed from the lack of access,
      late examination, and lack of guidance. Crude and adjusted analyses by Poisson
      regression assessed the association between outcomes and independent variables.
      RESULTS: The values of lack of access, late examination, and lack of guidance
      were 6.7%, 11.2%, and 19.2%, respectively. Problems of quality were lower
      according to the increase in Municipal Human Development Index and per capita
      household income, increasing with population size and municipal coverage of the
      Family Health Strategy. The Midwest region of the country presented the highest
      occurrences of low quality outcomes. Indigenous and yellow women had the highest
      prevalence of outcomes. Women with partner, who received the Bolsa Familia
      Program, and who had paid work had less chances of having lack of access, late
      examination, and lack of guidance. The appropriate work process in health
      services decreased the likelihood of low quality in all indicators. CONCLUSIONS:
      Investments in the work process of health teams, social cash transfer programs,
      and social conditions of the population are essential to improve the quality of
      the program of cervical cancer screening in Brazil. OBJETIVO: Analisar se as
      variaveis demograficas, socioeconomicas e da organizacao dos servicos estao
      associadas a qualidade do rastreamento do cancer de colo uterino. METODOS:
      Inquerito realizado em servicos de saude das cinco regioes brasileiras em 2012. A
      amostra foi composta por usuarias de unidades basicas de saude participantes do
      Programa de Melhoria do Acesso e da Qualidade na Atencao Basica. As variaveis
      independentes analisadas foram: caracteristicas socioeconomicas (contexto
      municipal); caracteristicas demograficas (perfil de usuarias); e dois dominios
      relativos a organizacao dos servicos basicos (estrutura e processo de trabalho).
      A baixa qualidade do rastreamento foi avaliada por meio da falta de acesso,
      atraso na realizacao do exame e falta de recebimento de orientacoes. Analises
      bruta e ajustada por meio de regressao de Poisson avaliaram a associacao entre os
      desfechos e as variaveis independentes. RESULTADOS: A falta de acesso, atraso na
      realizacao do exame e falta de recebimento de orientacoes foram de 6,7%, 11,2% e
      19,2%, respectivamente. Os problemas de qualidade foram menores de acordo com o
      aumento do Indice de Desenvolvimento Humano Municipal e da renda familiar per
      capita, aumentando com o porte populacional e a cobertura municipal da Estrategia
      Saude da Familia. A regiao Centro-Oeste do pais apresentou as maiores ocorrencias
      dos desfechos de baixa qualidade. As mulheres de raca indigena e amarela tiveram
      as maiores prevalencias dos desfechos. As mulheres com companheiro, que recebiam
      o beneficio do Programa Bolsa Familia e tinham trabalho remunerado tiveram menos
      falta de acesso, menos atraso na realizacao do exame e menos falta de recebimento
      de orientacoes. O processo de trabalho adequado nos servicos de saude diminuiu a
      probabilidade de baixa qualidade em todos os indicadores. CONCLUSOES:
      Investimentos em processo de trabalho das equipes de saude, programas sociais de
      transferencia de renda e condicoes sociais da populacao sao essenciais para
      melhorar a qualidade do programa de rastreamento de colo de utero no Brasil.

PMID- 28746578
TI  - [The principal contraceptive methods].
AB  - The author presents a summary-table showing the principal contraceptive methods,
      highlighting each one for effectiveness, advantages, disadvantages, collateral
      effects and recommendations for correct use. The author hopes it will he used as
      a guide by the nurses who quite are, frequently, requested to orient persons and
      couples about this subject.

PMID- 28746579
TI  - [Mental health team work in health centers: nurse's contribuition].
AB  - The author suggests that the public health nurse working in health centers, now
      in charge of mental health activities, insert in the actual health programs and
      sub-programs, aspects of mental health. It also refers to the need of including
      such aspects in the training and orientation of the nursing personnel.

PMID- 28746580
TI  - [The teaching of Psychiatry Nursing to undergraduate students in Brazil].
AB  - Historical retrospective of the teaching of Psychiatric Nursing in Brazil, in a
      Psychiatric Hospital of Rio de Janeiro, since the openning, of the first School
      of Nursing, until the present. The authors also try to identify the new concepts
      of this nursing speciality and the new trends of teaching it to undergraduate
      students.

PMID- 28746581
TI  - [Thoughts about the concepts self-care and self-care agency].
AB  - In this paper the author presents some aspects of Orem's self-care theory and
      discusses her views of self-care agency, utilizing a cognitive approach based on
      Perry's theory of cognitive development. Some studies which offer support to her
      approach are reviewed.

PMID- 28746582
TI  - [Specialization course in intensive care nursing of "Escola de Enfermagem da USP"
      - part 2: the learning-teaching process].
AB  - In this article, the authors describe the course's structure, methods and
      strategies applied to the learning-teaching process. Emphasis is given to the
      critical analyses and nursing research, within a proper environment for the
      exchange of experiences between teachers and students, looking for the
      improvement of professionals activing in intensive care units.

PMID- 28746583
TI  - [Reflections about the nurse's role in a pediatric intensive care unit: emotional
      aspects towards the family].
AB  - In this paper the author presents her philosophy of what is to be a nurse and her
      performance in a family - centered nursing approach. The nurse's need to
      experience professional situations and to learn about herself is here emphasized
      as a basic condition to understand the child its family so that together they can
      find solutions to the various situations lived in a pediatric intensive care
      unit.

PMID- 28746584
TI  - [Nursing activities in tne field of mental health].
AB  - It's not uncommon to hear complaints about the lack of speciafication of nursing
      interventions in Mental Health. Now a-days, with the emphasis given to
      multiprofessional work systems in that area, those complaints have increasead due
      to the belief that the system's efficiency also depends on the knowledge that
      each professional has about his share. Literature and this belief support us in
      offering a proposal of nurse's specific activities covering mental health
      approaches. We hope our contribution will help nurses to improve their
      participation when assisting clients.

PMID- 28746585
TI  - [Contents of Revista da Escola de Enfermagem da USP: period of 1967 to 1981].
AB  - The contents of the first fifteen volumes of Revista da Escola de Enfermagem da
      USP, are viewed as to type of matter published, their, themes, as well as the
      author's work field and academic degrees.

PMID- 28746586
TI  - [Contents of Revista da Escola de Enfermagem da USP: period of 1982 to 1986].
AB  - To celebrate the 20th aniversary of the Revista da Escola de Enfermagem da USP,
      the authors decided to extend to the years of 1982 - 1986 the analysis of the
      first fifteen years of the periodical, above published, made by STEFANELLI et
      alii.

PMID- 28746587
TI  - [MICROWAVE OVEN AS STERILIZATION APPLIANCE FOR MEDICAL-SURGICAL SUPPLIES].

PMID- 28746588
TI  - [Health programs text books for elementary and high schools: a critical
      comparative analysis].

PMID- 28746589
TI  - Mediastinal tumor: not always a lymphoma.

PMID- 28746590
TI  - Successful treatment of post-transplant relapsed acute myeloid leukemia with FLT3
      internal tandem duplication using the combination of induction chemotherapy,
      donor lymphocyte infusion, sorafenib and azacitidine. Report of three cases.
AB  - Acute myeloid leukemia is a hematopoietic stem cell neoplastic disease associated
      with high morbidity and mortality. The presence of FLT3 internal tandem
      duplication mutations leads to high rates of relapse and decreased overall
      survival. Patients with FLT3 internal tandem duplication are normally treated
      with hematopoietic stem cell transplantation in first complete remission.
      Nevertheless, the incidence of post-transplant relapse is considerable in this
      group of patients, and the management of this clinical condition is challenging.
      The report describes the outcomes of patients with FLT3 internal tandem
      duplication positive acute myeloid leukemia who relapsed after allogeneic
      hematopoietic stem cell transplantation and were treated with the combination of
      re-induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine.
      Three cases are described and all patients achieved prolonged complete remission
      with the combined therapy. The combination of induction chemotherapy followed by
      donor lymphocyte infusion, and the maintenance with azacitidine and sorafenib can
      be effective approaches in the treatment of post-hematopoietic stem cell
      transplant and relapsed FLT3 internal tandem duplication positive acute myeloid
      leukemia patients. This strategy should be further explored in the context of
      clinical trials.

PMID- 28746591
TI  - The therapeutic challenge of giant splenic artery aneurysm: a case repport.
AB  - Giant splenic artery aneurysm is a rare condition that represents an eminent life
      threatening for the patient, requiring, therefore, urgent surgical correction. A
      61-year-old woman, former smoker, hypertensive, hypercholesterolemic and
      multipara sought our service because of a large tumor in the mesogastrium, which
      was an abdominal ultrasound finding. Despite the size of the tumor, the patient
      was asymptomatic. The angiotomography and the magnetic resonance image of the
      abdomen were suggestive of giant splenic artery aneurysm with more than 10cm in
      diameter that was confirmed by an angiography. She underwent surgery, open
      splenectomy, and partial aneurysmectomy. The approach of the celiac artery, which
      was ligated, was only possible with medialvisceral rotation because there was no
      possibility to view it through the anterior access. The histopathological test of
      aneurysmatic wall revealed atheroma plaques in the intima. The patient progressed
      without complications and she was discharged cured. In general, giant splenic
      artery aneurysms are symptomatic, however, as in the case we report, it may be
      asymptomatic and found in abdominal imaging exam. Although less invasive
      Interventional methods exist, such as laparoscopy and endovascular techniques,
      they were considered inappropriate in this case. Conventional open surgery should
      be the therapy of choice for a giant splenic artery aneurysm.

PMID- 28746592
TI  - Endoscopic surveillance of extensive esophageal papillomatosis not amenable to
      endoscopic therapy.
AB  - We present two cases of esophageal papillomatosis, a very rare reported disease
      leading to dysphagia and did not improve after endoscopic treatment. Both
      patients refused surgery and they were followed-up for 3 years, but no
      significant clinical or endoscopic changes were seen.

PMID- 28746594
TI  - ?

PMID- 28746593
TI  - Ferritin light chain gene mutations in two Brazilian families with hereditary
      hyperferritinemia-cataract syndrome.
AB  - Hereditary hyperferritinemia-cataract syndrome is an autosomal dominant genetic
      disorder associated with mutations in the 5'UTR region of the ferritin light
      chain gene. These mutations cause the ferritin levels to increase even in the
      absence of iron overload. Patients also develop bilateral cataract early due to
      accumulation of ferritin in the lens, and many are misdiagnosed as having
      hemochromatosis and thus not properly treated. The first cases were described in
      1995 and several mutations have already been identified. However, this syndrome
      is still a poorly understood. We report two cases of unrelated Brazilian families
      with clinical suspicion of the syndrome, which were treated in our department.
      For the definitive diagnosis, the affected patients, their parents and siblings
      were submitted to Sanger sequencing of the 5'UTR region for detection of the
      ferritin light gene mutation. Single nucleotide polymorphism-like mutations were
      found in the affected patients, previously described. The test assisted in making
      the accurate diagnosis of the disease, and its description is important so that
      the test can be incorporated into clinical practice.

PMID- 28746595
TI  - [Retrospective analysis of nursing research in critical care nursing: 1975 to
      1984].
AB  - Nursing research in Intensive Care Units as compered to nursing research in other
      medical-surgical units, both in Brasil and in the United States, is the subject
      of this study. Data were collected from articles published in 1975, 1979 and 1984
      in "Revista Brasileira de Enfermagem" (for Brasil) and "Nursing Research" and
      "Heart and Lungs" (for USA). The analysis of data included type of study, its
      depth, metodology employed and selected subject. Increase in number of studies in
      nursing in Intensive Care Units, both descriptive and experimental, was observed.
      The authors also noted the absence of replication of research and of continuity
      studies.

PMID- 28746596
TI  - [Student - centered teaching: evolvement of the initial phase of the basic
      Pediatric Nursing Course].
AB  - The authors present a description of the evolvement of the initial phase of the
      Pediatric Nursing I Course, which, since 1979, utilizes the student - centered
      teaching methodology at the Nursing School of the Sao Paulo University.

PMID- 28746597
TI  - [Systematized evaluation of the teaching-learning process in medical-surgical
      nursing].
AB  - This is a study about the students' about the teaching - apprenticeship process
      used for Medical-Surgical Nursing at the University of Sao Paulo School of
      Nursing, and their evaluation of the program. It also contains students'
      suggestion on the teaching method employed.

PMID- 28746598
TI  - [Study on nurse performance evaluation: theoretical approach - Part I].
AB  - This first part of the study presents the literature on the evolution of
      personnel administration and discussess the organization/individual interaction
      from the mechanistic up to the systemic focusing. The systemic approach is based
      on the organization sociologic concept. The performance evaluation is studied as
      an integral part of human resources administration which in the health area, is
      considered a subsystem of the health system. The objectives of evaluation area
      analysed as well as the methods and techniques used, the training of the
      individuals participating in the evaluation process, the periodicity of the
      evaluation process and the feelings of both the evaluator and the evaluated
      person. As far as nursing is concerned it is underlined what has been done on
      nurse performance evaluation in other countries. The lack of studies on this
      subject in Brasil is stressed.

PMID- 28746599
TI  - [Social relations between the nursing team and the parents of hospitalized
      children].
AB  - By means of partially structured interviews and assistematic observation, the
      authors attempt to identify the types of social relations that occur between the
      nursing team and the parents visiting the hospitalized child.

PMID- 28746600
TI  - [Evaluation of the assistance given by a Nursing Assistance Center].
AB  - The Nursing Assistance was organized by the teachers of Medical-Surgical Nursing
      of the University of Sao Paulo (Brasil) School of Nursing. The evaluation was
      made by both clients-technical, administrative and domestic personnel of the
      School - and teachers responsible for the services. Both groups mentioned
      satisfaction with the attendance received or rendered and made suggestions for
      their improvement.

PMID- 28746602
TI  - ?

PMID- 28746601
TI  - [The risk sources in operating room: identification and evaluation].

PMID- 28746603
TI  - [Systematic orientation of outpatients with arterial hypertension].
AB  - This study was made in an outpatient treatment unit, with two groups of the
      patients with arterial hypertension and the objective was to identify the
      orientations about medications, diet, physical activity, smoke and drink
      alcoholic and to verify the reaction of the clients to systematic orientation by
      nurses. The results obtained had been presented in the tables distributed in the
      absolute and relative frequencies and analysed forward to the objectives of the
      study.

PMID- 28746604
TI  - [A study about a state-anxiety reduction through group dynamics].
AB  - State-anxiety was studied in a group of pediatric nurses who met to discuss their
      worries about work. State-anxiety was verified though the administration of State
      Trait Anxiety Inventory of SPIELBERG; the results indicated a significant
      reduction of state-anxiety at the end of the sessions.

PMID- 28746605
TI  - [Psychiatric nursing program for nurses in clinicai setting].
AB  - Because education is one of the means to bring about the process of change, a
      process extremely necessary in psychiatric nursing, the authors decided to find
      out the opinion of nurses in psychiatric hospitals about the recommended contents
      of a program of specialization on the subject, to be based on the difficulties
      found in their work.

PMID- 28746606
TI  - [Nursing: conceptual approaching].
AB  - The authors discuss some aspects of the concepts of values such as health and
      illness, theory and practice, professional power, image and space whith are the
      determinant factors of the concept of Nursing here presented.

PMID- 28746607
TI  - [The national conjuncture and the situation of the nurse].
AB  - This article introduces some preliminary considerations about Brazilian nursing
      and searches the articulation of the social practice with a specific structure
      and conjuncture. Then it analyses the nursing situation, identifying the
      heterogeneity which characterizes it, pointing out its contradictions; and
      finally it discusses the question of unions of nurses.

PMID- 28746608
TI  - [Considerations on floods and human leptospirosis in Sao Paulo City].
AB  - The occurence of floods in Sao Paulo is analysed in this article after the
      existing data on the 1983 outbreak of hitman leptospirosis. This problem deserves
      the attention and interest of sanitarians and politicians because of its danger
      to the people's health.

PMID- 28746609
TI  - [Study on nurse performance evaluation: obtained results and conclusions - Part
      III].
AB  - In this third part of this study the final part of the analysis, the discussion
      of the results and the conclusions are presented. The discussion involves the
      results regarding the specific professional capability of the evaluating nurses
      and of the respective evaluated nurses; the periodicity of the evaluations, the
      technics and methodology utilized by nurses in the evaluation process; the
      instruments used in the performance evaluation process and the reactions to the
      evaluation. The respective bibliography is presented along with the discussion of
      the results.

PMID- 28746610
TI  - [NURSING STUDENTS' LEARNING EXPERIENCE OF INTERACTION WITH PATIENTS].

PMID- 28746611
TI  - [NURSING STUDANTS' SEXUAL FORMATION, PRAXIS AND INTERESTS: PARTICIPANT RESEARCH
      AS AN EDUCATE PROCESS].

PMID- 28746612
TI  - Oxidative stress responses of juvenile tambaqui Colossoma macropomum after short
      term anesthesia with benzocaine and MS-222.
AB  - The present study aimed to evaluate the effects of benzocaine and tricaine
      methanesulfonate on oxidative stress parameters of juvenile tambaqui tissues.
      Fish (n=80) were anesthetized with benzocaine (100 mg L-1) or tricaine (240 mg L
      1) and two control groups were used (non-anesthetized fish and fish exposed to
      ethanol-only). After anesthetic induction 10 fish/anesthetic were euthanized
      after 3, 12 and 24 hours post-anesthesia and tissue samplings (gills, liver and
      brain) were performed. Samples were submitted to analyses of enzyme activity
      glutathione-S-transferase (GST), cellular lipid peroxidation (TBARS) and total
      antioxidant capacity (ACAP). ACAP increased in gills of benzocaine treatment
      after 12 hours. The liver showed a reduction in ACAP of tricaine treatment after
      12 hours. Both anesthetic treatments showed an increase of ACAP at 24 hours
      compared to control group. The activity of the GST enzyme increased in the gills
      for treatments benzocaine and tricaine after 3 and 12 hours. Liver showed
      increased GST activity (benzocaine after 24 hours and tricaine after 3 and 24
      hours). Lipid damage decreased in gills (both anesthetics) and brain (tricaine)
      after 24 hours. The results demonstrate that benzocaine and tricaine did not
      cause oxidative damage in juvenile tambaqui under the experimental conditions
      herein established.

PMID- 28746613
TI  - Crambe (Crambe abyssinica) and sunflower (Helianthus annuus) protein
      concentrates: production methods and nutritional properties for use in fish feed.
AB  - The purpose of this study was to develop and improve protein concentration
      techniques for two industrial by-products with the potential for use in fish
      feed. In particular, we chemically characterized crambe meal and sunflower meal
      and their protein concentrates. Three different protein concentration methods
      were tested: isoelectric pH (pHi), acid pH and alkaline pH. For crambe and
      sunflower meals extraction using the pHi method was most efficient in terms of
      protein yield and crude protein content in the concentrates; this method also
      increased lysine and methionine content in the concentrates. The water holding
      capacity of the sunflower protein concentrate was greater than that of the crambe
      protein concentrate. The crambe protein concentrate had a foam-formation capacity
      of 15%, which stabilized at 6% after 90 minutes. The protein concentration method
      also reduced total phenolic content by approximately 50% in the concentrates
      compared with the meals. Therefore, we conclude that protein concentration using
      the pHi method is the most efficient technique for crambe and sunflower meals,
      and the use of this technique can decrease total phenolic compounds while
      improving meal quality for fish feeding.

PMID- 28746614
TI  - Effects of nutritional conditions on lipid production by cyanobacteria.
AB  - The present study evaluated the effects of the culturing media and the levels of
      nitrogen and phosphorus on the growth, biomass productivity and lipid production
      of four species of Microcystis (M. novacekii, M. aeruginosa, M panniformis and M.
      protocystis). The lipid extract was obtained by refluxing with dichloromethane
      (Soxhlet). The biomass and biomass productivity yields were maximized with ASM-1
      medium treatment enriched with nitrogen and/or phosphorus (0.25-0.65 g/L and 25
      50.7 mg/L d-1, respectively). The lipid extract yields from M. panniformis and M.
      novacekii were inversely correlated with the concentration of nitrogen and
      directly correlated with the concentration of phosphorus (35.8 % and 31.7 %). The
      lipid extract yield from M. aeruginosa was inversely correlated with the nutrient
      concentration (23.3 %). M. protocystis exhibited a higher lipid content in the
      control medium (41.5 %) than in the nitrogen-enriched media. The recorded results
      show that a nutrient-poor culture medium favours cell growth and stimulates lipid
      accumulation, which directly affects the cost of cultivation by reducing nutrient
      consumption. All studied species may serve as biomass sources for biodiesel
      production, although M. protocystis exhibited the highest lipid production.
      Further studies are necessary to determine the composition of the recorded lipid
      extract.

PMID- 28746615
TI  - Estimated evolution of total pollutant gas emissions associated with vehicle
      activity in the Metropolitan Region of Porto Alegre until 2030.
AB  - In recent years, the majority of economic sectors in Brazil have gone through
      processes of development and transformation. These processes have led to
      increases in environmental pollution of all kinds; air pollution being one of the
      most adverse. The Brazilian transportation sector, which heavily affects the air
      quality, experienced a significant increase in its vehicle fleet thus provoking
      larger emissions of pollutant gases, mainly in regions with high population
      density such as the Metropolitan Region of Porto Alegre (MRPA). Within this
      research, considering mainly the ozone precursor species and Carbon Monoxide and
      using the year 2001 as a base year, scenarios are obtained for vehicular
      emissions of pollutant gases in the MRPA until the year 2030. In addition,
      scenarios related to the evolution of the study region's vehicle fleet were
      estimated. The statistical tool LEAP (Long Range Energy Alternatives Planning
      System) was used. The scenario analysis shows that the vehicle fleet will grow
      exponentially until 2030, considering that the Light Flex vehicles category will
      mainly contribute to this increase. It is also noted that vehicle emissions of
      CO, NOx, and THC decrease in the region. The decrease is caused mainly by the
      renewal of technology in new vehicles and the implementation of emission control
      programs created by the government.

PMID- 28746616
TI  - Biodiversity of Coreoidea and Pentatomidae (Heteroptera) from Atlantic forest
      protected areas. Insights into their conservation.
AB  - Although the majority of threatened species are likely to be tropical insects,
      knowledge of the diversity, ecological role and impact of insect biodiversity
      loss on ecosystem processes is very limited. Specimens belonging to four families
      of Heteroptera: Pentatomidae, Coreidae, Alydidae and Rhopalidae, were collected
      from a protected area in the Parana Forest, the largest ecoregion of the Atlantic
      Forest, in Argentina. The assemblages were characterized and the biodiversity
      estimated, and they were compared with the assemblages found in five other
      protected areas in the Brazilian Atlantic Forest. In our study area, Pentatomidae
      had the greatest richness and diversity; Coreidae was the second most diverse
      family, with highest sampling deficit, highest percentage of singletons, and
      lowest inventory completeness; and Rhopalidae was the best sampled family with
      asymptotic rarefaction curves. We explored the application of the Species
      Conservation Importance index, following four criteria, to evaluate the relative
      importance of the pentatomid species studied and its usefulness for assigning
      conservation values to areas. We found similar Site Conservation Values among the
      six areas and noted that the use of criteria was limited by the lack of
      information, being crucial to increase the knowledge of most of the species.

PMID- 28746617
TI  - Resistance of Xanthomonas euvesicatoria strains from Brazilian pepper to copper
      and zinc sulfates.
AB  - Bacterial spot, caused by Xanthomonas spp., is one of the major bacterial
      diseases in pepper (Capsicum annuum L.). The infection results in reduced crop
      yield, particularly during periods of high rainfall and temperature, due to the
      low efficiency of chemical control with copper bactericides. This study evaluated
      the copper and zinc sulfate sensitivity of 59 pathogenic strains of Xanthomonas
      euvesicatoria isolated from pepper plants produced in various regions throughout
      Brazil. Both the respective sulfates and a mixture thereof was evaluated at 50,
      100, 200 and 400 MUg.mL-1. All the evaluated strains were found to be resistant
      to zinc sulfate (100 MUg.mL-1) and 86.4% were resistant to copper sulfate (200
      MUg.mL-1). The mixture of copper (200 MUg.mL-1) and zinc (200 MUg.mL-1) sulfates
      inhibited the growth of all strains of X. euvesicatoria. To our knowledge this is
      the first study to report the resistance of X. euvesicatoria strains from pepper
      plants to copper and zinc sulfates in Brazil.

PMID- 28746618
TI  - Evidence of the Presence of Thyroid Hormones in Achatina fulica Snails.
AB  - The objective of this study was to identify thyroid hormones and to examine their
      putative site of synthesis in Achatina fulica snails. For this purpose,
      radioimmunoassays were performed for T3 and T4 before and after long starvation
      with or without hemolymph deproteinization. Sodium/iodide symporter activity in
      vivo was analyzed through 125I administration with and without KClO4
      pretreatment. Only T4 was detected, and its concentration decreased due to
      starvation or deproteinization. However, high-performance liquid chromatography
      analysis also showed the presence of T2 and T3 apart from T4, but rT3 was not
      detected in the A. fulica hemolymph. The sodium/iodide symporter activity was
      greater in cerebral ganglia than digestive gland, but KClO4 treatment did not
      inhibit iodide uptake in any of the tissues analyzed. Altogether, our data
      confirm for the first time the presence of thyroid hormones in A. fulica snails
      and suggest their participation in the metabolism control in this species,
      although the putative site of hormone biosynthesis remains to be elucidated.

PMID- 28746619
TI  - Floristic-functional variation of tree component along an altitudinal gradient in
      araucaria forest areas, in Southern Brazil.
AB  - We aimed to investigate the taxonomic and functional variations of tree component
      of Araucaria Forest (AF) areas located along an altitudinal gradient (700, 900
      and 1,600 m asl), in the southern region of Brazil. The functional traits
      determined were leaf area, specific leaf area, wood density, maximum potential
      height and dispersal syndromes and deciduousness. The data were analyzed through
      a functional and taxonomic dissimilarity dendrograms, community-weighted mean
      trait values, parametric and nonparametric tests, and Principal Component
      Analysis. The largest floristic-structural similarity was observed between the
      lower altitude areas (700 and 900 m asl), whose Bray-Curtis distance was 0.63.
      The area at 700 m asl was characterized by a predominance of deciduous and semi
      deciduous species, with a high number of self- and wind-dispersed species,
      whereas the area at 1,600 m asl exhibited a predominance of animal-dispersed and
      evergreen species. It was also observed that there were significant variations
      for leaf traits, basic wood density and maximum potential height. Over all
      altitudinal gradient, the ordinations indicated that there was no evidence of
      functional differentiation among dispersal and deciduousness groups. In
      conclusion, the evaluated Araucaria Forest areas presented high floristic
      functional variation of the tree component along the altitudinal gradient.

PMID- 28746620
TI  - Reproductive biology of the Green Ground Snake Erythrolamprus poecilogyrus
      sublineatus (Serpentes: Dipsadidae) in Subtropical Brazil.
AB  - We investigated reproductive features of the dipsadid snake Erythrolamprus
      poecilogyrus sublineatus in the southernmost Brazilian coast, a subtropical
      region characterized by well-marked seasons. Females are significantly smaller
      than males, have a shorter tail, and reach sexual maturity at later times along
      their development. In contrast to tropical subspecies, E. p. sublineatus females
      presented a seasonal pattern, with secondary follicles occurring from late winter
      to early autumn and egg production restricted to the whole spring and early
      summer. Males presented seasonal variation in testes volume (increase in autumn
      and decrease in winter) while no significant seasonal variation was found in
      ductus deferens width. The number of oviductal eggs varied from two to nine,
      thus, real fecundity is also inferior than that observed in tropical E.
      poecilogyrus forms. Considering the thermal requirements for reproduction, it is
      possible that the colder climatic conditions of the southern Brazilian coast have
      shaped the seasonal reproductive pattern in E. p. sublineatus. The shorter body
      size of this subspecies may also represent a conditioning factor of low
      fecundity.

PMID- 28746621
TI  - Morphological affinities of Homo naledi with other Plio-Pleistocene hominins: a
      phenetic approach.
AB  - Recent fossil material found in Dinaledi Chamber, South Africa, was initially
      described as a new species of genus Homo, namely Homo naledi. The original study
      of this new material has pointed to a close proximity with Homo erectus. More
      recent investigations have, to some extent, confirmed this assignment. Here we
      present a phenetic analysis based on dentocranial metric variables through
      Principal Components Analysis and Cluster Analysis based on these fossils and
      other Plio-Pleistocene hominins. Our results concur that the Dinaledi fossil
      hominins pertain to genus Homo. However, in our case, their nearest neighbors are
      Homo habilis and Australopithecus sediba. We suggest that Homo naledi is in fact
      a South African version of Homo habilis, and not a new species. This can also be
      applied to Australopithecus sediba.

PMID- 28746622
TI  - Holocene history of a lake filling and vegetation dynamics of the Serra Sul dos
      Carajas, southeast Amazonia.
AB  - Down-core changes in sedimentary facies, elemental geochemistry, pollen, spore,
      delta13C, delta15N and radiocarbon records from a filled lake, named R4, of the
      Serra Sul dos Carajas were used to study the relationship between the
      paleomorphological and paleoecological processes and their significance for
      Holocene paleoclimatology of the southeast Amazonia. The sediment deposition of
      the R4 lake started around 9500 cal yr BP. Increase of detrital components from
      9500 to 7000 cal yr BP suggests high weathering of surrounding catchment rocks
      and soils, and deposition into the lake basin under mudflows. At that time,
      montane savanna and forest formation were already established suggesting
      predominance of wet climate. However, from 7000 to 3000 cal yr BP, a decline of
      detrital input occurred. Also, forest formation and pteridophytes were declined,
      while palms and macrophytes were remained relatively stable, indicating that
      water levels of the lake is likely dropped allowing the development of plants
      adapted to subaerial condition under drier climate conditions. After 3000 cal yr
      BP, eutrophication and low accommodation space lead to high lake productivity and
      the final stage of the lake filling respectively, and forest formation may has
      acquired its current structure, which suggests return of wetter climate
      conditions.

PMID- 28746623
TI  - Extreme cultural persistence in eastern-central Brazil: the case of Lagoa Santa
      Paleaeoindians.
AB  - Lapa do Santo rockshelter, a Paleoindian site located in Eastern-Central Brazil,
      presented two main occupations; one during Early Holocene (12,460 to 8700 cal
      BP), and a latter in Middle Holocene (5100 to 4200 cal BP). In spite of this 3600
      year gap, the stratigraphy and general characteristics of the material culture
      did not indicate any visible discontinuity. This led us to hypothesise a
      reoccupation of the rockshelter by the same cultural group, tested by means of
      statistical analyses comparing lithics, bone artifacts, and faunal remains from
      early and middle Holocene layers. No significant differences were found, and our
      results indicate the presence of a cultural tradition that persisted for 8240
      years, or roughly 412 generations.

PMID- 28746624
TI  - In vitro antifungal activity of Myracrodruon urundeuva Allemao against human
      vaginal Candida species.
AB  - Myracrodruon urundeuva is a plant native to Brazil, which is used by the
      indigenous population for the treatment of candidiasis. The aims of this study
      were to evaluate the antifungal activity of extract against human vaginal Candida
      species and evaluate the possible toxicological activities of M. urundeuva.
      Initially, ethanol extracts, ethyl acetate fractions, and hydroalcoholic
      fractions of the bark and leaf of M. urundeuva were used to determine the minimum
      inhibitory concentration. The extracts that showed antifungal activity were
      characterized by liquid chromatography and subjected to toxicity assessment.
      Toxic, cytotoxic, genotoxic, and mutagenic testing were performed using Allium
      cepa and Ames assays with the ethanol extracts of the bark and leaves. Hemolytic
      activity was evaluated in erythrocytes and acute toxicity in rats. The ethanol
      bark extracts showed best activity against Candida albicans, C. krusei, and C.
      tropicalis ATCC (4-512 ug/mL). Chemical characterization indicated the presence
      of flavonoids and tannins in the extracts. Hemolytic activity, genotoxicity, and
      mutagenicity were not observed. The results of the Ames and A. cepa tests were
      also in agreement, ethanol bark extracts and ethanol leaf extracts of M.
      urundeuva showed absence of mutagenic activity. Similar results were observed in
      the A. cepa assay and acute toxicity test in rats. M. urundeuva bark extracts
      showed potential for the treatment of vaginal infections caused Candida species,
      as a topical.

PMID- 28746625
TI  - ?

PMID- 28746626
TI  - [The following of the graduated in nursing].
AB  - In this study the authors identify the nurses' difficulties at the begining of
      their professional activities, and evaluate the type of education offered by
      their undergraduate nursing program.

PMID- 28746627
TI  - [Play: a way to understand the hospitalized child].
AB  - Play in hospitals is a resource that facilitates the child's experience of
      hospitalization. Furthermore it is a valiable instrument of information to the
      health staff. The author presents a study where she can have elements to the
      comprehension of hospitalized child's needs through therapeutic play.

PMID- 28746628
TI  - [Research by rooming-in mothers: reflections upon the results].
AB  - The author presents her reflections upon the results she obtained in research by
      rooming-in mothers, in which assistance and teaching - learning aspects are
      included.

PMID- 28746629
TI  - [Nursing care to the premature some basics procedures].
AB  - The basics procedures of nursing care to the premature are presented here. They
      are: observation of the premature during the first 24 hours of life, hidratation
      by bottle, feeding by nosogastric tube, care of premature after feeding,
      tecnnique of bathing the premature in the incubator, care of premature skin to
      avoid from infection, care of the umbilical stump, care of premature with
      moniliasis, with respiratory distress, with diarrhea, with vomitus, cleaning and
      preservation of the incubator, care of the premature who is receving oxigen
      therapy, control of humidity of the incubator, care of the premature under
      phototherapy, care with the phototherapy equipment.

PMID- 28746630
TI  - [CARI Project - Assistance proposal in children's institutions].
AB  - The authors present a plan they call "CARI Project". "CARI Project" is a work
      with babies and their mothers in children's institutions. Its objective is to
      decrease the infant morbidity and mortality rates by means of: observation of the
      growth measurements, stimulating breast-feeding, oral hydratation and
      immunizations. The teaching of the four techniques to mothers is suggested.

PMID- 28746631
TI  - [The undergraduate course of Pediatric Nursing offered at the School of Nursing
      of the University of Sao Paulo].
AB  - Based upon the motives that led the group of instructors of pediatric nursing to
      adopt a new teaching methodology, the authors present the current characteristics
      of the Pediatric Nursing baccalaureate course of the University of Sao Paulo
      School of Nursing as well as the form in which the course is being implemented.

PMID- 28746632
TI  - [Influence of the factors that raise satisfaction and dissatisfaction to nurses
      motivation on job environment].

PMID- 28746633
TI  - ?

PMID- 28746634
TI  - [Nursing care to the woman in the perinatal period - psychosocial aspect].
AB  - The authors describe the components of obstetrical nursing as the woman in the
      perinatal period, the existent problem, the context where the woman is assisted
      and the nursing care that is given to her. The emphasis is placed in the
      therapeutic nurse-patient relationship. The authors present instruments to
      support nursing care as observation, interviews, domiciliary visit, and the
      record of these three itens. To assure, as far as possible, the well-being of the
      binomial mother-child the nurse has to develope functions as guidance,
      therapeutic nurse-patient relationship, and crisis intervention.

PMID- 28746635
TI  - [Rooming-in: which mothers may remain with their sick children during
      hospitalization in Pediatric Units?]
AB  - Pediatric nurses for decision making about wich mothers may accompany their sick
      children during hospitalization, in a unit that allows rooming-in, are analized
      by the author. Some considerations are also made about accomodations offered to
      these mothers.

PMID- 28746636
TI  - [Empathy - a phenomenological approach].
AB  - The author presents some concepts of empathy according to some authors and the
      difficulties to perform these concepts. The empathy is suggested to study as a
      phenomenon by a phenomenologic method and through the envolvement between nurse
      and patient during the moment the patient passed away.

PMID- 28746637
TI  - [Nursing concept - an attempt of phenomenological approach].
AB  - The authors present a brief literature review about the phenomenological approach
      in nursing research. This issue is an attempt in phenomenological analysis of the
      concept of nursing. The answers to the question "what is nursing?", made by 251
      nurses, were grouped in categories and compared with HENDERSON'S and HORTA's
      nursing concepts.

PMID- 28746638
TI  - [The use of intravenous oxytocin in deliveries nursing assistance].
AB  - This paper emphasizes the importance of specialized nursing assistance to the
      woman in labor when contractions are stimulated by infusion containing oxytocin.
      The author describes the procedures recommended in the litterature for the
      treatment and for control of mother and child conditions during the firts phase
      of delivery.

PMID- 28746639
TI  - [The external reader in specialized Library].
AB  - From the affirmative that the Library is important because it is an essential
      part of knowledge and that the Specialized University Library of a Teaching
      Institution must contain bibliographical material to support the disciplines
      within the studies they have to offer; we have elaborated an users study which
      includes individuals that are not registered as regular students at the
      Institution. The objectives of it have been directed to the users,
      characterization, issues of search, and the use of information and opinions about
      the Library. The instrument that has been used was a questionnaire containing
      subjectives and objectives questions. The results have demonstrated that the
      objectives proposed were attained. We have also presented analized comments about
      the opinions given by the users. We have reached the conclusion that studies of
      such kind should be elaborated and evaluated regarding the necessity of the user
      / informations in the different existing Libraries.

PMID- 28746640
TI  - [Process of decision making in nursing in a University - Hospital. Preliminary
      study].
AB  - This work presents the results obtained on the first of a series of studies about
      the Process of Decision making in nursing. The results herein described are the
      automatic and deliberative decisions made by nurses when attending patients in
      the University Hospital of Santa Catarina Federal University. Brazil.

PMID- 28746641
TI  - [Nursing scientific production presented at the annual meetings of the Brazilian
      Society for the Development of Science].
AB  - The authors have analized the scientific production presented by nurses and other
      professionals associated with the teaching of Nursing, published in the ANNALS of
      the Yearly Meetings of the Brazilian Society for Science Development (SBPC) from
      1949 to 1983. Data showed a prevalence of papers prepared by faculty members over
      those prepared by Nursing Service Staff, as well a tendency for a quantitative
      decrease in the scientific production in the last five years.

PMID- 28746642
TI  - [Emotional envolvement in the nurse-patient relationship].
AB  - This article gives emphasis to the importance of the emotional envolvement during
      the nurse-patient relationship in a Psychiatry Hospital. The author, a nursing
      student, describes her own fears and doubts and how, with the help of her
      instructors, she overcame them and was able to develop a therapeutic
      relationship.

PMID- 28746643
TI  - [Study of intestinal irrigation of colostomy patients: previous note].
AB  - The author relates the problems of colostomy patient during the rehabilitation,
      intestinal control, adequate equipment and skin care. She refers to the control
      of intestinal habit with colostomy irrigation and relates comparative studies
      that demonstrated the efficiency and superiority of this method in relation to
      natural evacuation. She proposes an experimental sistematized study with
      adaptable and cheap equipment which will not interfere in the therapeutic effect
      of colostomy and will be used in hospital, ambulatory and at home. The data of
      this study is being collected in the Proctology Ambulatorial Service of a General
      Hospital.

PMID- 28746644
TI  - ?

PMID- 28746645
TI  - ?

PMID- 28746646
TI  - [Study of nursing teaching in common diseases in Brazil].
AB  - The authors of the given work, present the result of a study (investigation)
      carried out in 27 Schools of Nursing and Obstetrics in Brazil and about how the
      subject 'infections diseases " is taught and administered.

PMID- 28746647
TI  - [Students as proctors: a experience in Fundamental of Nursing].
AB  - Three advanced students were used as proctors in Fundamentals of Nursing for the
      academic periods of 1981 and 1982. Results are presented and the opinions of
      both, the proctors and oriented students, are discussed.

PMID- 28746648
TI  - [Growth rate and development in feed restricted female rats].
AB  - Age and weight were determined by direct measure in 30 feed-restricted female
      rats studied from weaning to first estrus, and compared to well fed controls. At
      the first estrus the average weight of well fed rats did not differ from that of
      the feed-restricted groups. Mean ages at vaginal opening and first estrus in the
      feed-restricted animals were however greater.

PMID- 28746649
TI  - [Continued education in public health nursing].
AB  - This paper deals with the theoretical aspects of continued education: concepts,
      characteristics and relationship to adult education, as well as modalities of
      methods and technics. It also emphasizes some significant aspects of continued
      education in public health nursing.

PMID- 28746650
TI  - [Student-centered teaching: an experience told by nursing studentes being taught
      under this method].
AB  - Four master's degree nursing students tell of their learning experience in a
      pediatric nursing program based on student-centered teaching methodology. The
      students relate their initial doubts about the effectivity of the methodology,
      the difficulties they encountered in formulating a program to be followed, and
      their observations of the behavior and the attitudes presented by their teacher
      facilitator. In order to attain their particular learning objectives for the
      program, the group chose to start an experiment involving maternal-child care in
      a slum area of sao Paulo. The students and their teacher worked with mothers and
      other adults responsible for child care, using nondirective communication In this
      paper it's possible to identify the different necessary elements for a program
      The authors believe that the main result of this experiment on them wor theer
      accomphisment as individuals and as professionals, as well as their own
      development as persons.

PMID- 28746651
TI  - [The learning of basic nursing procedures a comparision of two methods].
AB  - A comparision of the learning of basic nursing procedures was experimentally
      investigated. The main objectives were: a) to verify it students trained in
      nursing laboratory make less mistakes in their first real situation than those
      who had not similar training; b) to evaluate mursin laboratory training through a
      self-instructional strategy as compared with the traditional strategy. Sixty-four
      female students enrolled in the Fundamentals of Nursing Course were investigated
      They had no prior experience with bladder catheterization. All 64 students were
      thoroughly evaluated on the subject taugh after they were exposed both to
      lectures and practical demonstration. Three groups were formed A group A of 25,
      who received no training in the nursing laboratory was taken as control; a second
      group, B of 20 students, received the traditional training in the nursing
      laboratory; group C was composed of 19 students and their nursing laboratory
      training followed a self-instructional strategy. Each nursing student performed a
      bladder catheterization in a patient. A nurse-instructor supervised each student
      performance and assessed her mistakes. Following statistical analysis of the data
      it can be shown that: - No significant higher number of mistakes was made by
      group A (control) as compared with group BC groups B and C togethers and the same
      occurred to group B as compared with group C - Age and scores evaluation test,
      number of mistakes committed, and scores evaluation test or age were not
      statistically associated. - Similar mistakes were made by students of all three
      groups. - Time required for self-instruction varied greatly among students, but
      no association could be established with age, number of mistakes or scores
      evaluation test. - Most students praised highly self-instruction strategy and
      calimed that for better results should be adopted in the reaching of other
      laboratory procedures.

PMID- 28746652
TI  - [The patient in the surgical unit system: study about perceptions and opinions of
      patients relating to the transoperatory period].
AB  - The author made a study about the perceptions and opinions of the patient, during
      the period of transoperatory, in relation with the fisical human surroudings of
      the surgical system in three hospitals in Londrina.

PMID- 28746653
TI  - ?

PMID- 28746654
TI  - [A portuguese THESAURUS for nursing].

PMID- 28746655
TI  - Smoking control in Brazil: a public health success story.

PMID- 28746656
TI  - Mortality due to noncommunicable diseases in Brazil, 1990 to 2015, according to
      estimates from the Global Burden of Disease study.
AB  - CONTEXT AND OBJECTIVE:: Noncommunicable diseases (NCDs) are the leading health
      problem globally and generate high numbers of premature deaths and loss of
      quality of life. The aim here was to describe the major groups of causes of death
      due to NCDs and the ranking of the leading causes of premature death between 1990
      and 2015, according to the Global Burden of Disease (GBD) 2015 study estimates
      for Brazil. DESIGN AND SETTING:: Cross-sectional study covering Brazil and its 27
      federal states. METHODS:: This was a descriptive study on rates of mortality due
      to NCDs, with corrections for garbage codes and underreporting of deaths.
      RESULTS:: This study shows the epidemiological transition in Brazil between 1990
      and 2015, with increasing proportional mortality due to NCDs, followed by
      violence, and decreasing mortality due to communicable, maternal and neonatal
      causes within the global burden of diseases. NCDs had the highest mortality rates
      over the whole period, but with reductions in cardiovascular diseases, chronic
      respiratory diseases and cancer. Diabetes increased over this period. NCDs were
      the leading causes of premature death (30 to 69 years): ischemic heart diseases
      and cerebrovascular diseases, followed by interpersonal violence, traffic
      injuries and HIV/AIDS. CONCLUSION:: The decline in mortality due to NCDs confirms
      that improvements in disease control have been achieved in Brazil. Nonetheless,
      the high mortality due to violence is a warning sign. Through maintaining the
      current decline in NCDs, Brazil should meet the target of 25% reduction proposed
      by the World Health Organization by 2025.

PMID- 28746657
TI  - Characterization of the first symptoms of multiple sclerosis in a Brazilian
      center: cross-sectional study.
AB  - CONTEXT AND OBJECTIVE:: Multiple sclerosis (MS) is a chronic, immune-mediated and
      degenerative central nervous system (CNS) disease with well-established
      diagnostic criteria. Treatment can modify the course of the disease. The
      objective of this study was to describe the initial symptoms of multiple
      sclerosis in a Brazilian medical center. DESIGN AND SETTING:: Descriptive study,
      conducted in a Brazilian reference center for multiple sclerosis treatment.
      METHODS:: Data on 299 patients with confirmed diagnoses of MS were included in
      the study. Their medical files were evaluated and the data were analyzed.
      RESULTS:: The most common symptom involved the cranial nerves (50.83%) and
      unifocal manifestation was presented by the majority of this population (73.91%).
      The mean time between the first symptom and the diagnosis was 2.84 years.
      Unifocal symptoms correlated with longer time taken to establish the diagnosis,
      with an average of 3.20 years, while for multifocal symptoms the average time
      taken for the diagnosis was 1.85 years. Unifocal onset was related to greater
      diagnostic difficulty. CONCLUSIONS:: MS is a heterogeneous disease and its
      initial clinical manifestation is very variable.

PMID- 28746658
TI  - Relationship between periodontal disease and cardiovascular risk factors among
      young and middle-aged Brazilians. Cross-sectional study.
AB  - CONTEXT AND OBJECTIVE:: It has been suggested in the literature that periodontal
      disease (PD) is associated with cardiovascular risk. The objective of this study
      was to appraise the relationship between periodontal disease (gingivitis and
      periodontitis) and traditional cardiovascular risk factors (obesity,
      hypertension, dyslipidemia, diabetes and metabolic syndrome) among young and
      middle-aged adults attended at a health promotion and check-up center in the city
      of Sao Paulo, Brazil. DESIGN AND SETTING:: Cross-sectional study at the Health
      Promotion and Check-up Center of Hospital Sirio-Libanes, Sao Paulo, Brazil.
      METHODS:: We consecutively evaluated 539 subjects without prior cardiovascular
      disease who were seen within a health promotion program that included
      cardiovascular and dental evaluation between February and November 2012. Odds
      ratios (OR) with respective 95% confidence intervals (95% CI) for the association
      between PD and cardiovascular risk factors were ascertained through multinomial
      logistic regression. RESULTS:: In this sample of mean age 45 years (standard
      deviation, SD +/- 8.8), which was 82% male, we found PD in 63.2% (gingivitis
      50.6% and periodontitis 12.6%). Individuals with PD were older, more obese
      (without PD 15.2%; versus gingivitis 22.1% and periodontitis 32.4%) and more
      diabetic (without PD 5.1%; versus gingivitis 4.8% and periodontitis 13.2%),
      compared with those without PD. Among all cardiovascular risk factors evaluated,
      obesity was associated with periodontitis (multivariate OR, 2.36; 95% CI, 1.23
      4.52). However, after additional adjustment for oral hygiene, this finding was no
      longer significant (multivariate OR, 1.63; 95% CI, 0.79-3.37). CONCLUSIONS:: We
      did not find any significant associations between cardiovascular risk factors and
      periodontal disease in this sample.

PMID- 28746659
TI  - Comparison of machine-learning algorithms to build a predictive model for
      detecting undiagnosed diabetes - ELSA-Brasil: accuracy study.
AB  - CONTEXT AND OBJECTIVE:: Type 2 diabetes is a chronic disease associated with a
      wide range of serious health complications that have a major impact on overall
      health. The aims here were to develop and validate predictive models for
      detecting undiagnosed diabetes using data from the Longitudinal Study of Adult
      Health (ELSA-Brasil) and to compare the performance of different machine-learning
      algorithms in this task. DESIGN AND SETTING:: Comparison of machine-learning
      algorithms to develop predictive models using data from ELSA-Brasil. METHODS::
      After selecting a subset of 27 candidate variables from the literature, models
      were built and validated in four sequential steps: (i) parameter tuning with
      tenfold cross-validation, repeated three times; (ii) automatic variable selection
      using forward selection, a wrapper strategy with four different machine-learning
      algorithms and tenfold cross-validation (repeated three times), to evaluate each
      subset of variables; (iii) error estimation of model parameters with tenfold
      cross-validation, repeated ten times; and (iv) generalization testing on an
      independent dataset. The models were created with the following machine-learning
      algorithms: logistic regression, artificial neural network, naive Bayes, K
      nearest neighbor and random forest. RESULTS:: The best models were created using
      artificial neural networks and logistic regression. -These achieved mean areas
      under the curve of, respectively, 75.24% and 74.98% in the error estimation step
      and 74.17% and 74.41% in the generalization testing step. CONCLUSION:: Most of
      the predictive models produced similar results, and demonstrated the feasibility
      of identifying individuals with highest probability of having undiagnosed
      diabetes, through easily-obtained clinical data.

PMID- 28746660
TI  - Somatic maturation and the relationship between bone mineral variables and types
      of sports among adolescents: cross-sectional study.
AB  - CONTEXT AND OBJECTIVE:: Peak height velocity (PHV) is an important maturational
      event during adolescence that affects skeleton size. The objective here was to
      compare bone variables in adolescents who practiced different types of sports,
      and to identify whether differences in bone variables attributed to sports
      practice were dependent on somatic maturation status. DESIGN AND SETTING:: Cross
      sectional study, Sao Paulo State University (UNESP). METHODS:: The study was
      composed of 93 adolescents (12 to 16.5 years old), divided into three groups: no
      sport group (n = 42), soccer/basketball group (n = 26) and swimming group (n =
      25). Bone mineral density and content were measured using dual-energy x-ray
      absorptiometry and somatic maturation was estimated through using peak height
      velocity. Data on training load were provided by the coaches. RESULTS::
      Adolescents whose PHV occurred at an older age presented higher bone mineral
      density in their upper limbs (P = 0.018). After adjustments for confounders, such
      as somatic maturation, the swimmers presented lower values for bone mineral
      density in their lower limbs, spine and whole body. Only the bone mineral density
      in the upper limbs was similar between the groups. There was a negative
      relationship between whole-body bone mineral content and the weekly training
      hours (beta: -1563.967; 95% confidence interval, CI: -2916.484 to -211.450).
      CONCLUSION:: The differences in bone variables attributed to sport practice
      occurred independently of maturation, while high training load in situations of
      hypogravity seemed to be related to lower bone mass in swimmers.

PMID- 28746661
TI  - Postural balance and functional independence of elderly people according to
      gender and age: cross-sectional study.
AB  - CONTEXT AND OBJECTIVE:: Aging causes changes in men and women. Studies have shown
      that women have worse postural balance and greater functional dependence than
      men, but there is no consensus regarding this. The aim of this study was to
      compare the balance and functional independence of elderly people according to
      sex and age, and to evaluate the association between postural balance and the
      number of drugs taken. DESIGN AND SETTING:: Cross-sectional at a state
      university. METHODS:: 202 elderly people were evaluated regarding balance (Berg
      Scale), independence (Barthel Index), age, sex, number of medications and
      physical activity. RESULTS:: The subjects comprised 117 women (70.2 +/- 5.6 years
      old) and 85 men (71.1 +/- 6.9 years old). For balance, there was no significant
      difference regarding sex, but there was a difference regarding age (P < 0.0001).
      For functional independence, there was a difference regarding sex (P = 0.003),
      but not regarding age. The variables of age, medications and physical activity
      were significant for predicting the Berg score. For the Barthel index, only age
      and sex were significant. Elderly people who took three or more medications/day
      showed higher risk of falling than those who took up two drugs/day (odds ratio =
      5.53, P < 0.0001, 95% confidence interval, 2.3-13.0). CONCLUSIONS:: There was no
      sexual difference in relation to postural balance. However, people who were more
      elderly presented a high risk of falling. Functional dependence was worse among
      females. There was an association between the number of medication drugs and risk
      of falling.

PMID- 28746662
TI  - Age at first childbirth and newly diagnosed diabetes among postmenopausal women:
      a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health
      (ELSA-Brasil).
AB  - CONTEXT AND OBJECTIVE:: It has been reported that earlier age at first childbirth
      may increase the risk of adult-onset diabetes among postmenopausal women, a novel
      finding with important public health implications. To date, however, no known
      studies have attempted to replicate this finding. We aimed to test the hypothesis
      that age at first childbirth is associated with the risk of adult-onset diabetes
      among postmenopausal women. DESIGN AND SETTING:: Cross-sectional analysis using
      baseline data from 2919 middle-aged and elderly postmenopausal women in the
      Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS:: Age at
      first childbirth was determined from self-reporting and newly diagnosed diabetes
      through a 2-hour 75-g oral glucose tolerance test and/or glycated hemoglobin.
      Logistic regression was performed to examine associations between age at first
      childbirth and newly diagnosed diabetes among postmenopausal women. RESULTS:: We
      did not find any association between age at first childbirth and diabetes, either
      when minimally adjusted for age, race and study center (odds ratio, OR [95%
      confidence interval, CI]: <= 19 years: 1.15 [0.82-1.59], 20-24 years: 0.90 [0.66
      1.23] and >= 30 years: 0.86 [0.63-1.17] versus 25-29 years; P = 0.36) or when
      fully adjusted for childhood and adult factors (OR [95% CI]: <= 19 years: 0.95
      [0.67-1.34], 20-24 years: 0.78 [0.56-1.07] and >= 30 years: 0.84 [0.61-1.16]
      versus 25-29 years; P = 0.40). CONCLUSION:: Our current analysis does not support
      the existence of an association between age at first childbirth and adult-onset
      diabetes among postmenopausal women, which had been reported previously.

PMID- 28746663
TI  - Hospitalizations due to primary care-sensitive conditions among children under
      five years of age: cross-sectional study.
AB  - CONTEXT AND OBJECTIVE:: Hospitalizations due to primary care-sensitive conditions
      constitute an important indicator for monitoring the quality of primary
      healthcare. This study aimed to describe hospitalizations due to primary care
      sensitive conditions found among children under five years of age (according to
      their age and sex), in two cities in Paraiba, Brazil. DESIGN AND SETTING:: Cross
      sectional study carried out in the municipalities of Cabedelo and Bayeux, in
      Paraiba, Brazil. METHODS:: Data were collected from four public pediatric
      hospitals in Paraiba that receive children from these municipalities. Hospital
      admission authorizations were consulted to gather information on the children's
      profile and the characteristics of their hospitalizations. Differences in the
      causes of admissions and the respective lengths of hospital stay length were
      analyzed according to age group and sex. RESULTS:: The proportion of hospital
      admissions due to primary care-sensitive conditions was 82.4%. The most frequent
      causes were: bacterial pneumonia (59.38%), infectious gastroenteritis and its
      complications (23.59%) and kidney and urinary tract infection (9.67%). Boys had
      higher frequency of hospitalizations due to primary care-sensitive conditions
      than girls. The median hospitalization due to primary care-sensitive conditions
      was found to be four days. The duration of hospital stays due to primary care
      sensitive conditions was significantly longer than those due to conditions that
      were not sensitive to primary care. CONCLUSIONS:: High rates of hospital
      admissions due to primary care-sensitive conditions were highlighted, especially
      among children of male sex, with long periods of hospitalization.

PMID- 28746664
TI  - What do Cochrane systematic reviews say about non-pharmacological interventions
      for treating cognitive decline and dementia?
AB  - BACKGROUND:: Dementia is a highly prevalent condition worldwide. Its chronic and
      progressive presentation has an impact on physical and psychosocial
      characteristics and on public healthcare. Our aim was to summarize evidence from
      Cochrane reviews on non-pharmacological treatments for cognitive disorders and
      dementia. DESIGN AND SETTING:: Review of systematic reviews, conducted in the
      Discipline of Evidence-Based Medicine, Escola Paulista de Medicina, Universidade
      Federal de Sao Paulo. METHODS:: Cochrane reviews on non-pharmacological
      interventions for cognitive dysfunctions and/or type of dementia were included.
      For this, independent assessments were made by two authors. RESULTS:: Twenty-four
      reviews were included. These showed that carbohydrate intake and validation
      therapy may be beneficial for cognitive disorders. For dementia, there is a
      potential benefit from physical activity programs, cognitive training,
      psychological treatments, aromatherapy, light therapy, cognitive rehabilitation,
      cognitive stimulation, hyperbaric oxygen therapy in association with donepezil,
      functional analysis, reminiscence therapy, transcutaneous electrical stimulation,
      structured decision-making on feeding options, case management approaches,
      interventions by non-specialist healthcare workers and specialized care units. No
      benefits were found in relation to enteral tube feeding, acupuncture, Snoezelen
      stimulation, respite care, palliative care team and interventions to prevent
      wandering behavior. CONCLUSION:: Many non-pharmacological interventions for
      patients with cognitive impairment and dementia have been studied and potential
      benefits have been shown. However, the strength of evidence derived from these
      studies was considered low overall, due to the methodological limitations of the
      primary studies.

PMID- 28746665
TI  - ?

PMID- 28746666
TI  - [Causes of emotional stress on nurses assisting critically ill children].
AB  - This is a pilot study on the causes of emotional stress on 13 nurses working in
      Pediatric Intensive Care Units. The Author identified, as extrinsic causes, the
      objectives and the environment of the units, the relations nurse-members of the
      working team, the family and the children's critical condition; and, as intrinsic
      causes, the nurses personal conditions and their attitude towards death.

PMID- 28746667
TI  - [Popular use of medicinal plants in infancy: implications for nursing].
AB  - An exploratory study is made by nurses -with a group of mothers with the purpose
      of identifying reasons for the popular use of medicinal plants by mothers caring
      for their children within the 0-2 years age range. Influence of the social,
      economical and cultural factores involved are considered. The implications of
      this data for nursing care and for teaching it are described.

PMID- 28746668
TI  - [The influence of nutrition on age menarche].
AB  - The onset of menarche is later in Brazilian girls than in American and European
      girls. According to the Author one of the causes is the difference in nutritions
      due to different social-economical levels.

PMID- 28746669
TI  - [Nursing care to patients with obsessive-compulsive symptoms].
AB  - The authors discuss the usual behavior patterns of neurotic patients with
      obsessive-compulsive symptoms, the meaning of this behavior and some of the main
      points in nursing care.

PMID- 28746670
TI  - [Opinion of nursing students about some sexual practices].
AB  - The objectives of this study were to find out about the beliefs of nursing
      students near graduation on some aspects of human sexuality, the sources of their
      information on the subject and the persons they considered as having influenced
      their opinion The data obtained are compared with the results of similar studies
      made among the general population.

PMID- 28746671
TI  - [Preparation of nurses for supervision in health centers].
AB  - The authors describe an experiment on cooperation between a school of nursing 
      through instructors and some students enrollded in the Public Health Nursing
      Program - and from Regional Health Centers. The objective was to experiment the
      application of a "model" of supervision of nursing personnel and of continued
      education. The most important conclusion was the need of close cooperation
      between educational arid service institutions for efficient preparation of the
      working personnel.

PMID- 28746673
TI  - ?

PMID- 28746672
TI  - [Interactions between nurses and parents of hospitalized children].
AB  - With the purpose of supplying subsidies to nurses who work in pediatric wards,
      and using observation as method, the author attempts to analise and comment the
      interactions that occur between nurses and parents of hospitalized children in
      different, but usual situations during the hospitalization of children.

PMID- 28746674
TI  - ?

PMID- 28746675
TI  - ?

PMID- 28746676
TI  - ?

PMID- 28746677
TI  - ?

PMID- 28746678
TI  - ?

PMID- 28746679
TI  - ?
AB  - The purposes of the present study were to: a) assess the nurses' opinions and
      experience (about) with Horta's theory and nursing process, and b) compare the
      current faculty's opinions about nursing process teaching with the faculty's
      opinions gathered in 1979. The sample consisted of 49 nursing faculty members and
      43 nurses who worked at an hospital. The data were collected through a
      questionnaire. The findings showed that the Theory of Basic Human Needs proposed
      by Horta was the model most used in the nursing education and practice settings
      at the Federal University of Santa Catarina.

PMID- 28746680
TI  - ?

PMID- 28746681
TI  - ?

PMID- 28746682
TI  - ?

PMID- 28746683
TI  - ?

PMID- 28746684
TI  - ?

PMID- 28746685
TI  - ?

PMID- 28746686
TI  - ?

PMID- 28746687
TI  - [Nursing care for the newborns with congenital Chagas' disease].
AB  - In Brazil, due to the urbanization of the rural diseases, the health services
      must be prepared to detect precociously the infections, control the propagation
      and attend these sick people. The authors did a bibliographic surveying about
      congenital Chagas' disease, presented a study with a good evolution, tried to
      determine the nursing care to these newborns and the respectives objectives.

PMID- 28746688
TI  - [Teaching communication therapeutic techniques in nurse-patient relationship:
      conceptual basis - Part II].
AB  - The conceptual basis used in this research are presented in this papers. The
      author presents the basis concepts underlying human communication theory,
      therapeutic communication and interpersonal relationship.

PMID- 28746689
TI  - [Research in pediatric nursing].
AB  - This work give informations about modalities of research in pediatric nursing
      realized to obtain academical title from 1975 to 1985, in Brazil.

PMID- 28746690
TI  - [The relationship among theory, research and practice in nursing].
AB  - The present study is an attempt to present a process of relationship among
      theory, research, and practice in nursing. First, the term theory is defined as
      well as each of the theory's basic elements. Secondly, the concepts of research
      and practice are discussed in terms of their potential for stemming, testing, and
      redefining the theory. Thirdly, the concepts of theory, research and practice are
      presented as a triple spiral which works as a dinamic process. Within this
      process the theory, research, and practice interact to improve each other.

PMID- 28746691
TI  - [The pre-operative nursing assessment of patients by the operating room nurses].
AB  - The objective of this survey is to verify how many Sao Paulo hospitals which
      employ operating room nurses, proceed in having pre-operative nursing assessment
      of patients. This procedure is essencial to assure a continuous nursing
      assistance and basic to patient-needs centered nursing care. Results found show
      that the majority of nurses although knowing about the importance of the
      procedure, do not implement it.

PMID- 28746692
TI  - [Nursing performance in an orthopedic and traumatology emergency service].
AB  - To determine the adequary of nursing assistance to population demand, the authors
      developed a brief survey of the actual physical area, nursing personnel,
      equipament and supply of the Orthopedic and Traumatology Emergency Service where
      the study is been done.

PMID- 28746693
TI  - [Public health nursing in leprosy control: knowledge of nursing personal].
AB  - This work is a report of a research carried out in the Sanitary Dermatology 
      Leprosy area of the Health Centers from the Regional Health Department of
      Ribeirao Preto, State Health Bureau of Sao Paulo State. The investigation pointed
      out the knowledge of nursing personal which directly operated in the area,
      establishing that the correct knowledge ranged from 86,8% to 60,4% for "notions
      on the illness" and "notions on experiments and tests" items, having the complete
      answers also presented coefficient superior to the incomplete ones. However, the
      number of "wrong" and "doesn't know" answers were significant, according to the
      classification carried through each item.

PMID- 28746694
TI  - [The research situation in brazilian psychiatric nursing].
AB  - In their practice the authors observed a lack of research results in psychiatric
      nursing, brought to the nurses assistence activities. This fact stimulated them
      to survey the existent studies done in Brazil, in order to verify what has been
      investigated in the area. Data collection covered Brazilian nursing periodicals,
      theses and dissertations. Bringing to focus the themes already researched, the
      objective of this article is twofold: to stimulate nurses to incorporate the
      provided research knowledge to their practice, and to undertake new studies to
      meliorate psychiatric nursing care quality.

PMID- 28746695
TI  - [A nursing Thesaurus in Portuguese: elaboration of a descriptive vocabulary -
      Part one.]
AB  - The relevance of the issue and the publication of descriptive vocabularies by
      several disciplines, as a mean to classify published information, motivated the
      authors to develop a similar experience for the nursing discipline. The objective
      of the present study is the elaboration of a descriptive vocabulary, that can be
      used by the public in the search of information, by librarians when doing the
      classification of bibliographical themes and by documentalists when preparing
      resumees. Procedures are described and long, mediun and short range goals for the
      implementation of a Brazilian Nursing are commented.

PMID- 28746696
TI  - [Occupational stress and the operating room nurse: preliminary not].

PMID- 28746698
TI  - Missing Conflict of Interest Disclosure.

PMID- 28746697
TI  - [Nurse's role concerning the planning of human reproduction: Preliminary note].

PMID- 28746699
TI  - Association of Risk of Suicide Attempts With Methylphenidate Treatment.
AB  - Importance: Patients with attention-deficit/hyperactivity disorder (ADHD) are at
      an increased risk of attempting suicide. Stimulants, such as methylphenidate
      hydrochloride, are the most common treatment for ADHD, but the association
      between their therapeutic use and suicide is unclear. Objective: To investigate
      the association between methylphenidate and the risk of suicide attempts. Design,
      Setting, and Participants: A population-based, electronic medical records
      database from the Hong Kong Clinical Data Analysis & Reporting System was used to
      identify 25 629 individuals aged 6 to 25 years who were treated with
      methylphenidate between January 1, 2001, and December 31, 2015. Those who had
      attempted suicide were included in the analysis. A self-controlled case series
      design was used to control for time-invariant characteristics of the patients.
      Main Outcomes and Measures: Relative incidence of suicide attempt during periods
      when patients were exposed to methylphenidate compared with nonexposed periods.
      Results: Among 25 629 patients with methylphenidate prescriptions, 154 had their
      first recorded suicide attempt within the study period; of these individuals, 111
      (72.1%) were male; mean (SD) age at baseline was 7.15 (2.19) years. The overall
      incidence of suicide attempts during methylphenidate treatment was 9.27 per 10
      000 patient-years. An increased risk of suicide attempts was detected during the
      90-day period before methylphenidate was initiated, with an incidence rate ratio
      (IRR) of 6.55 (95% CI, 3.37-12.72). The IRR remained elevated during the first 90
      days of treatment (IRR, 3.91; 95% CI, 1.62-9.42) before returning to baseline
      levels during ongoing treatment (IRR, 1.35; 95% CI, 0.77-2.38). When the risk
      during the first 90 days of treatment was compared with the 90 days preceding
      first treatment, the incidence of suicide attempts was not elevated (IRR, 0.78;
      95% CI, 0.26-2.35). Conclusions and Relevance: The incidence of suicide attempts
      was higher in the period immediately before the start of methylphenidate
      treatment. The risk remained elevated immediately after the start of
      methylphenidate treatment and returned to baseline levels during continuation of
      methylphenidate treatment. The observed higher risk of suicide attempts before
      treatment may reflect emerging psychiatric symptoms that trigger medical
      consultations that result in a decision to begin ADHD treatment. Therefore, this
      study's results do not support a causal association between methylphenidate
      treatment and suicide attempts.

PMID- 28746700
TI  - Risk Factors for Melanoma in Renal Transplant Recipients.
AB  - Importance: Melanoma risk factors and incidence in renal transplant recipients
      can inform decision making for both patients and clinicians. Objective: To
      determine risk factors and characteristics of renal transplant recipients who
      develop melanoma. Design, Setting, and Participants: This cohort study of a large
      national data registry used a cohort of renal transplant recipients from the
      United States Renal Data System (USRDS) database from the years 2004 through
      2012. Differences in baseline characteristics between those who did and did not
      develop melanoma were examined, and a survival analysis was performed. Patients
      with renal transplants who received a diagnosis of melanoma according to any
      inpatient or outpatient claim associated with a billing code for melanoma were
      included. A history of pretransplant melanoma, previous kidney transplantation,
      or transplantation after 2012 or before 2004 were exclusion criteria. The data
      analysis was conducted from 2015 to 2016. Exposure: Receipt of a renal
      transplant. Main Outcomes and Measures: Incidence and risk factors for melanoma.
      Results: Of 105 174 patients (64 151 [60.7%] male; mean [SD] age, 49.6 [15.3]
      years) who received kidney transplants between 2004 and 2012, 488 (0.4%) had a
      record of melanoma after transplantation. Significant risk factors for developing
      melanoma vs not developing melanoma included older age among recipients (mean
      [SD] age, 60.5 [10.2] vs 49.7 [15.3] years; P < .001) and donors (42.6 [15.0] vs
      39.2 [15.1] years; P < .001), male sex (71.5% vs 60.7%; P < .001), recipient
      (96.1% vs 66.5%; P < .001) and donor (92.4% vs 82.9%; P < .001) white race, less
      than 4 HLA mismatches (44.9% vs 37.1%; P = .001), living donors (44.7% vs 33.7%;
      P < .001), and sirolimus (22.3% vs 13.2%; P < .001) and cyclosporine (4.9% vs
      3.2%; P = .04) therapy. Risk factors significant on survival analysis included
      older recipient age (hazard ratio [HR] per year, 1.06; 95% CI, 1.05-1.06; P <
      .001), recipient male sex (HR, 1.53; 95% CI, 1.25-1.88; P < .001), recipient
      white race, living donors (HR, 1.35; 95% CI, 1.11-1.64; P = .002), and sirolimus
      (HR, 1.54; 95% CI, 1.22-1.94; P < .001) and cyclosporine (HR, 1.93; 95% CI, 1.24
      2.99; P = .004) therapy. The age-standardized relative rate of melanoma in USRDS
      patients compared with Surveillance, Epidemiology, and End Results patients
      across all years was 4.9. A Kaplan-Meier estimate of the median time to melanoma
      among those patients who did develop melanoma was 1.45 years (95% CI, 1.31-1.70
      years). Conclusions and Relevance: Renal transplant recipients had greater risk
      of developing melanoma than the general population. We believe that the risk
      factors we identified can guide clinicians in providing adequate care for
      patients in this vulnerable group.

PMID- 28746701
TI  - Can We Reap the Benefits of Regionalization Without Paying the Price?

PMID- 28746703
TI  - Treatment of Elastosis Perforans Serpiginosa Using a Fractional Carbon Dioxide
      Laser.

PMID- 28746702
TI  - Identifying an Optimal Adjuvant Radiotherapy Dose for Extremity and Trunk Merkel
      Cell Carcinoma Following Resection: An Analysis of the National Cancer Database.
AB  - Importance: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous
      neuroendocrine neoplasm with a high risk of recurrence following resection.
      Despite a rising incidence over the past 3 decades, there is a paucity of
      prospective data owing to the rarity of this disease. Objective: To determine the
      optimal adjuvant radiation therapy (RT) dose following resection of localized MCC
      of the extremities or trunk. Design, Setting, and Participants: Using the
      National Cancer Database, a large national database consisting of a heterogeneous
      population and treatment settings, we retrospectively analyzed a cohort of 2093
      patients 18 years or older with stage I to III MCC of the extremities and/or
      trunk treated with definitive surgery and adjuvant RT between 1998 and 2011.
      Exclusion criteria included receiving treatment with palliative intent,
      preoperative RT, non-external-beam RT, and radiation dose of 30 Gy or lower or 70
      Gy or higher. Cox proportional hazards regression model was used to compare
      overall survival (OS) between RT dose groups, accounting for age, sex, race,
      stage, surgery type, margin status, comorbidities, and use of chemotherapy.
      Exposures: Radiation therapy dose was categorized into 4 groups: group 1 received
      the lowest dose (>30 to <40 Gy); group 2, the next lowest (40 to <50 Gy); group
      3, the second highest dose (50 to 55 Gy); and group 4, the highest dose (>55 to
      70 Gy). Main Outcome and Measure: Overall survival. Results: Data from 2093
      patients were analyzed; there were 1293 men (61.8%) and 800 women (38.2%) (median
      age, 73 years). After a median follow-up of 37 months for the entire cohort, 904
      deaths were reported. The 3-year OS rates for groups 1, 2, 3, and 4 were 41.8%,
      69%, 69.2%, and 66%, respectively (omnibus P < .001). Compared with group 3 (50
      to 55 Gy), equivalent OS was seen in group 2 (40 to <50 Gy; adjusted hazard ratio
      [AHR], 0.89; 95% CI, 0.63-1.27; P = .52) and group 4 (>55 to 70 Gy; AHR, 1.18;
      95% CI, 0.93-1.48; P = .17), but worse OS was found in group 1 (>30 to <40 Gy;
      AHR, 2.63; 95% CI, 1.44-4.80; P < .001). Conclusions and Relevance: Adjuvant RT
      dose from 40 to lower than 50 Gy appears adequate for extremities and/or trunk
      stage I to III MCC, with OS equivalent to that found at higher-dose regimens (>50
      to 70 Gy).

PMID- 28746704
TI  - Role of Preventability in Redefining Failure to Rescue Among Major Trauma
      Patients.

PMID- 28746705
TI  - Risk of Suicide Attempt Among Soldiers in Army Units With a History of Suicide
      Attempts.
AB  - Importance: Mental health of soldiers is adversely affected by the death and
      injury of other unit members, but whether risk of suicide attempt is influenced
      by previous suicide attempts in a soldier's unit is unknown. Objective: To
      examine whether a soldier's risk of suicide attempt is influenced by previous
      suicide attempts in that soldier's unit. Design, Setting, and Participants: Using
      administrative data from the Army Study to Assess Risk and Resilience in
      Servicemembers (STARRS), this study identified person-month records for all
      active-duty, regular US Army, enlisted soldiers who attempted suicide from
      January 1, 2004, through December 31, 2009 (n = 9650), and an equal-probability
      sample of control person-months (n = 153 528). Data analysis was performed from
      August 8, 2016, to April 10, 2017. Main Outcomes and Measures: Logistic
      regression analyses examined the number of past-year suicide attempts in a
      soldier's unit as a predictor of subsequent suicide attempt, controlling for
      sociodemographic features, service-related characteristics, prior mental health
      diagnosis, and other unit variables, including suicide-, combat-, and
      unintentional injury-related unit deaths. The study also examined whether the
      influence of previous unit suicide attempts varied by military occupational
      specialty (MOS) and unit size. Results: Of the final analytic sample of 9512
      enlisted soldiers who attempted suicide and 151 526 control person-months, most
      were male (86.4%), 29 years or younger (68.4%), younger than 21 years when
      entering the army (62.2%), white (59.8%), high school educated (76.6%), and
      currently married (54.8%). In adjusted models, soldiers were more likely to
      attempt suicide if 1 or more suicide attempts occurred in their unit during the
      past year (odds ratios [ORs], 1.4-2.3; P < .001), with odds increasing as the
      number of unit attempts increased. The odds of suicide attempt among soldiers in
      a unit with 5 or more past-year attempts was more than twice that of soldiers in
      a unit with no previous attempts (OR, 2.3; 95% CI, 2.1-2.6). The association of
      previous unit suicide attempts with subsequent risk was significant whether
      soldiers had a combat arms MOS or other MOS (ORs, 1.4-2.3; P < .001) and
      regardless of unit size, with the highest risk among those in smaller units (1-40
      soldiers) (ORs, 2.1-5.9; P < .001). The population-attributable risk proportion
      for 1 or more unit suicide attempts in the past year indicated that, if this risk
      could be reduced to no unit attempts, 18.2% of attempts would not occur.
      Conclusions and Relevance: Risk of suicide attempt among soldiers increased as
      the number of past-year suicide attempts within their unit increased for combat
      arms and other MOSs and for units of any size but particularly for smaller units.
      Units with a history of suicide attempts may be important targets for preventive
      interventions.

PMID- 28746706
TI  - Association Between Preoperative Hemoglobin A1c Levels, Postoperative
      Hyperglycemia, and Readmissions Following Gastrointestinal Surgery.
AB  - Importance: Preoperative hyperglycemia is associated with adverse postoperative
      outcomes among patients who undergo surgery. Whether preoperative hemoglobin A1c
      (HbA1c) or postoperative glucose levels are more useful in predicting adverse
      events following surgery is uncertain in the current literature. Objective: To
      examine the use of preoperative HbA1c and early postoperative glucose levels for
      predicting postoperative complications and readmission. Design, Setting, and
      Participants: In this observational cohort study, inpatient gastrointestinal
      surgical procedures performed at 117 Veterans Affairs hospitals from 2007 to 2014
      were identified, and cases of known infection within 3 days before surgery were
      excluded. Preoperative HbA1c levels were examined as a continuous and categorical
      variable (<5.7%, 5.7%-6.5%, and >6.5%). A logistic regression modeled
      postoperative complications and readmissions with the closest preoperative HbA1c
      within 90 days and the highest postoperative glucose levels within 48 hours of
      undergoing surgery. Main Outcomes and Measures: Postoperative complications and
      30-day unplanned readmission following discharge. Results: Of 21 541
      participants, 1193 (5.5%) were women, and the mean (SD) age was 63.7 (10.6)
      years. The cohort included 23 094 operations with measurements of preoperative
      HbA1c levels and postoperative glucose levels. The complication and 30-day
      readmission rates were 27.2% and 14.7%, respectively. In logistic regression
      models adjusting for HbA1c, postoperative glucose levels, postoperative insulin
      use, diabetes, body mass index (calculated as weight in kilograms divided by
      height in meters squared), and other patient and procedural factors, peak
      postoperative glucose levels of more than 250 mg/dL were associated with
      increased 30-day readmissions (odds ratio, 1.18; 95% CI, 0.99-1.41; P = .07). By
      contrast, a preoperative HbA1c of more than 6.5% was associated with decreased 30
      day readmissions (odds ratio, 0.85; 95% CI, 0.74-0.96; P = .01). As preoperative
      HbA1c increased, the frequency of 48-hour postoperative glucose checks increased
      (4.92, 6.89, and 9.71 for an HbA1c <5.7%, 5.7%-6.4%, and >6.5%, respectively; P <
      .001). Patients with a preoperative HbA1c of more than 6.5% had lower thresholds
      for postoperative insulin use. Conclusions and Relevance: Early postoperative
      hyperglycemia was associated with increased readmission, but elevated
      preoperative HbA1c was not. A higher preoperative HbA1c was associated with
      increased postoperative glucose level checks and insulin use, suggesting that
      heightened postoperative vigilance and a lower threshold to treat hyperglycemia
      may explain this finding.

PMID- 28746707
TI  - Erythematous, Burning and Painful Scrotal Nodules.

PMID- 28746708
TI  - Effectiveness and Safety of Dementia Care Management in Primary Care: A
      Randomized Clinical Trial.
AB  - Importance: Dementia care management (DCM) can increase the quality of care for
      people with dementia. Methodologically rigorous clinical trials on DCM are
      lacking. Objective: To test the effectiveness and safety of DCM in the treatment
      and care of people with dementia living at home and caregiver burden (when
      available). Design, Setting, and Participants: This pragmatic, general
      practitioner-based, cluster-randomized intervention trial compared the
      intervention with care as usual at baseline and at 12-month follow-up. Simple 1:1
      randomization of general practices in Germany was used. Analyses were intent to
      treat and per protocol. In total, 6838 patients were screened for dementia
      (eligibility: 70 years and older and living at home) from January 1, 2012, to
      March 31, 2016. Overall, 1167 (17.1%) were diagnosed as having dementia, and 634
      (9.3%) provided written informed consent to participate. Interventions: Dementia
      care management was provided for 6 months at the homes of patients with dementia.
      Dementia care management is a model of collaborative care, defined as a complex
      intervention aiming to provide optimal treatment and care for patients with
      dementia and support caregivers using a computer-assisted assessment determining
      a personalized array of intervention modules and subsequent success monitoring.
      Dementia care management was targeted at the individual patient level and was
      conducted by 6 study nurses with dementia care-specific qualifications. Main
      Outcomes and Measures: Quality of life, caregiver burden, behavioral and
      psychological symptoms of dementia, pharmacotherapy with antidementia drugs, and
      use of potentially inappropriate medication. Results: The mean age of 634
      patients was 80 years. A total of 407 patients received the intended treatment
      and were available for primary outcome measurement. Of these patients, 248
      (60.9%) were women, and 204 (50.1%) lived alone. Dementia care management
      significantly decreased behavioral and psychological symptoms of dementia (b = 
      7.45; 95% CI, -11.08 to -3.81; P < .001) and caregiver burden (b = -0.50; 95% CI,
      -1.09 to 0.08; P = .045) compared with care as usual. Patients with dementia
      receiving DCM had an increased chance of receiving antidementia drug treatment
      (DCM, 114 of 291 [39.2%] vs care as usual, 31 of 116 [26.7%]) after 12 months
      (odds ratio, 1.97; 95% CI, 0.99 to 3.94; P = .03). Dementia care management
      significantly increased quality of life (b = 0.08; 95% CI, 0 to 0.17; P = .03)
      for patients not living alone but did not increase quality of life overall. There
      was no effect on potentially inappropriate medication (odds ratio, 1.86; 95% CI,
      0.62 to 3.62; P = .97). Conclusions and Relevance: Dementia care management
      provided by specifically trained nurses is an effective collaborative care model
      that improves relevant patient- and caregiver-related outcomes in dementia.
      Implementing DCM in different health care systems should become an active area of
      research. Trial Registration: clinicaltrials.gov Identifier: NCT01401582.

PMID- 28746710
TI  - Clinical Outcomes of Metastatic Melanoma Treated With Checkpoint Inhibitors and
      Multisite Radiotherapy.

PMID- 28746709
TI  - Association of Coronary Artery Calcium Score vs Age With Cardiovascular Risk in
      Older Adults: An Analysis of Pooled Population-Based Studies.
AB  - Importance: Besides age, other discriminators of atherosclerotic cardiovascular
      disease (ASCVD) risk are needed in older adults. Objectives: To examine the
      predictive ability of coronary artery calcium (CAC) score vs age for incident
      ASCVD and how risk prediction changes by adding CAC score and removing only age
      from prediction models. Design, Setting, and Participants: We conducted an
      analysis of pooled US population-based studies, including the Framingham Heart
      Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health
      Study. Results were compared with 2 European cohorts, the Rotterdam Study and the
      Heinz Nixdorf Recall Study. Participants underwent CAC scoring between 1998 and
      2006 using cardiac computed tomography. The participants included adults older
      than 60 years without known ASCVD at baseline. Exposures: Coronary artery calcium
      scores. Main Outcomes and Measures: Incident ASCVD events including coronary
      heart disease (CHD) and stroke. Results: The study included 4778 participants
      from 3 US cohorts, with a mean age of 70.1 years; 2582 (54.0%) were women, and
      2431 (50.9%) were nonwhite. Over 11 years of follow-up (44 152 person-years), 405
      CHD and 228 stroke events occurred. Coronary artery calcium score (vs age) had a
      greater association with incident CHD (C statistic, 0.733 vs 0.690; C statistics
      difference, 0.043; 95% CI of difference, 0.009-0.075) and modestly improved
      prediction of incident stroke (C statistic, 0.695 vs 0.670; C statistics
      difference, 0.025; 95% CI of difference, -0.015 to 0.064). Adding CAC score to
      models including traditional cardiovascular risk factors, with only age being
      removed, provided improved discrimination for incident CHD (C statistic, 0.735 vs
      0.703; C statistics difference, 0.032; 95% CI of difference, 0.002-0.062) but not
      for stroke. Coronary artery calcium score was more likely than age to provide
      higher category-free net reclassification improvement among participants who
      experienced an ASCVD event (0.390; 95% CI, 0.312-0.467 vs 0.08; 95% CI -0.001 to
      0.181) and to result in more accurate reclassification of risk for ASCVD events
      among these individuals. The findings were similar in the 2 European cohorts (n =
      4990). Conclusions and Relevance: Coronary artery calcium may be an alternative
      marker besides age to better discriminate between lower and higher CHD risk in
      older adults. Whether CAC score can assist in guiding the decision to initiate
      statin treatment for primary prevention in older adults requires further
      investigation.

PMID- 28746711
TI  - Suicidal Behaviors Within Army Units: Contagion and Implications for Public
      Health Interventions.

PMID- 28746712
TI  - Half-century After "Summer of Love," Free Clinics Still Play Vital Role.

PMID- 28746713
TI  - Ischemic Postconditioning During Primary Percutaneous Coronary Intervention: Is
      Smoker's Paradox in Play?

PMID- 28746714
TI  - Association of Hospital Market Concentration With Costs of Complex
      Hepatopancreaticobiliary Surgery.
AB  - Importance: Trade-offs involved with market competition, overall costs to payers
      and consumers, and quality of care have not been well defined. Less competition
      within any given market may enable provider-driven increases in charges.
      Objective: To examine the association between regional hospital market
      concentration and hospital charges for hepatopancreaticobiliary surgical
      procedures. Design, Setting, and Participants: This study included all patients
      undergoing hepatic or pancreatic resection in the Nationwide Inpatient Sample
      from January 1, 2003, through December 31, 2011. Hospital market concentration
      was assessed using a variable-radius Herfindahl-Hirschman Index (HHI) in the
      2003, 2006, and 2009 Hospital Market Structure files. Data were analyzed from
      November 19, 2016, through March 2, 2017. Interventions: Hepatic or pancreatic
      resection. Main Outcomes and Measures: Multivariable mixed-effects log-linear
      models were constructed to determine the association between HHI and total costs
      and charges for hepatic or pancreatic resection. Results: Weighted totals of 38
      711 patients undergoing pancreatic resection (50.8% men and 49.2% women; median
      age, 65 years [interquartile range, 55-73 years]) and 52 284 patients undergoing
      hepatic resection (46.8% men and 53.2% women; median age, 59 years [interquartile
      range, 49-69 years]) were identified. Higher institutional volume was associated
      with lower cost of pancreatic resection (-5.4%; 95% CI, -10.0% to -0.5%; P = .03)
      and higher cost of hepatic resection (13.4%; 95% CI, 8.2% to 18.8%; P < .001).
      For pancreatic resections, costs were 5.5% higher (95% CI, 0.1% to 11.1%; P =
      .047) in unconcentrated hospital markets relative to moderately concentrated
      markets, although overall charges were 8.3% lower (95% CI, -14.0% to -2.3%; P =
      .008) in highly concentrated markets. For hepatic resections, hospitals in highly
      concentrated markets had 8.4% lower costs (95% CI, -13.0% to -3.6%; P = .001)
      compared with those in unconcentrated markets and charges that were 13.4% lower
      (95% CI, -19.3% to -7.1%; P < .001) compared with moderately concentrated markets
      and 10.5% lower (95% CI, -16.2% to -4.4%; P = .001) compared with unconcentrated
      markets. Conclusions and Relevance: Higher market concentration was associated
      with lower overall charges and lower costs of pancreatic and hepatic surgery. For
      complex, highly specialized procedures, hospital market consolidation may
      represent the best value proposition: better quality of care with lower costs.

PMID- 28746716
TI  - It's About the Weight Loss.

PMID- 28746717
TI  - An Incidental Hypervascular Retroperitoneal Mass.

PMID- 28746715
TI  - Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the
      Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General
      Cognitive Function.
AB  - Importance: Schizophrenia is associated with widespread cognitive impairments.
      Although cognitive deficits are one of the factors most strongly associated with
      functional outcome in schizophrenia, current treatment strategies largely fail to
      ameliorate these impairments. To develop more efficient treatment strategies in
      patients with schizophrenia, a better understanding of the pathogenesis of these
      cognitive deficits is needed. Accumulating evidence indicates that genetic risk
      of schizophrenia may contribute to cognitive dysfunction. Objective: To identify
      genomic regions jointly influencing schizophrenia and the cognitive domains of
      reaction time and verbal-numerical reasoning, as well as general cognitive
      function, a phenotype that captures the shared variation in performance across
      cognitive domains. Design, Setting, and Participants: Combining data from genome
      wide association studies from multiple phenotypes using conditional false
      discovery rate analysis provides increased power to discover genetic variants and
      could elucidate shared molecular genetic mechanisms. Data from the following
      genome-wide association studies, published from July 24, 2014, to January 17,
      2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort
      (n = 79 757 [cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n =
      36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general
      cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic
      Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27
      888). Main Outcomes and Measures: Genetic loci identified by conditional false
      discovery rate analysis. Brain messenger RNA expression and brain expression
      quantitative trait locus functionality were determined. Results: Among the
      participants in the genome-wide association studies, 21 loci jointly influencing
      schizophrenia and cognitive traits were identified: 2 loci shared between
      schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia
      and reaction time, and 14 loci shared between schizophrenia and general cognitive
      function. One locus was shared between schizophrenia and 2 cognitive traits and
      represented the strongest shared signal detected (nearest gene TCF20; chromosome
      22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 * 10-7),
      general cognitive function (z score, -4.43; P = 9.42 * 10-6), and verbal
      numerical reasoning (z score, -5.43; P = 5.64 * 10-8). For 18 loci, schizophrenia
      risk alleles were associated with poorer cognitive performance. The implicated
      genes are expressed in the developmental and adult human brain. Replicable
      expression quantitative trait locus functionality was identified for 4 loci in
      the adult human brain. Conclusions and Relevance: The discovered loci improve the
      understanding of the common genetic basis underlying schizophrenia and cognitive
      function, suggesting novel molecular genetic mechanisms.

PMID- 28746719
TI  - MACRA and Cardiology-The Devil Is in the Details.

PMID- 28746718
TI  - Association of Incident Amelanotic Melanoma With Phenotypic Characteristics, MC1R
      Status, and Prior Amelanotic Melanoma.
AB  - Importance: We previously reported that survival is poorer from
      histopathologically amelanotic than pigmented melanoma because of more advanced
      stage at diagnosis. Identifying patients at risk of amelanotic melanoma might
      enable earlier diagnosis and improved survival; however, the phenotypic
      characteristics and underlying genetics associated with amelanotic melanoma are
      unknown. Objective: To determine whether phenotypic characteristics, carriage of
      MC1R variants, and history of amelanotic melanoma are associated with
      histopathologically amelanotic melanoma. Design, Setting, and Participants: The
      Genes, Environment, and Melanoma (GEM) study is an international cohort study
      that enrolled patients with incident primary cutaneous melanomas from population
      based and hospital-based cancer registries (1998 to 2003). The GEM participants
      included here were 2387 patients with data for phenotypes, MC1R genotype, and
      primary melanomas scored for histopathologic pigmentation. Of these 2387 patients
      with incident melanomas scored for pigmentation, 527 had prior primary melanomas
      also scored for pigmentation. Main Outcomes and Measures: Associations of
      phenotypic characteristics (freckles, nevi, phenotypic index) and MC1R status
      with incident amelanotic melanomas were evaluated using logistic regression
      models adjusted for age, sex, study center, and primary status (single or
      multiple primary melanoma); odds ratios (ORs) and 95% CIs are reported.
      Association of histopathologic pigmentation between incident and prior melanomas
      was analyzed using an exact logistic regression model. Results: This study
      included 2387 patients (1065 women, 1322 men; mean [SD] age at diagnosis, 58.3
      [16.1] years) and 2917 primary melanomas. In a multivariable model including
      phenotypic characteristics, absence of back nevi, presence of many freckles, and
      a sun-sensitive phenotypic index were independently associated with amelanotic
      melanoma. Carriage of MC1R variants was associated with amelanotic melanoma but
      lost statistical significance in a model with phenotype. Further, patients with
      incident primary amelanotic melanomas were more likely to have had a prior
      primary amelanotic melanoma (OR, 4.62; 95% CI, 1.25-14.13) than those with
      incident primary pigmented melanomas. Conclusions and Relevance: Absence of back
      nevi, presence of many freckles, a sun-sensitive phenotypic index, and prior
      amelanotic melanoma increase odds for development of amelanotic melanoma. An
      increased index of suspicion for melanoma in presenting nonpigmented lesions and
      more careful examination for signs of amelanotic melanoma during periodic skin
      examination in patients at increased odds of amelanotic melanoma might lead to
      earlier diagnosis and improved survival.

PMID- 28746720
TI  - Clinical Care Across Cultures: What Helps, What Hinders, What to Do.

PMID- 28746721
TI  - Association Between Administration of Ticagrelor and Microvascular Endothelial
      Function.

PMID- 28746722
TI  - Ischemic Postconditioning During Primary Percutaneous Coronary Intervention: Is
      Smoker's Paradox in Play?-Reply.

PMID- 28746723
TI  - Factors Associated With Achieving a Body Mass Index of Less Than 30 After
      Bariatric Surgery.
AB  - Importance: Achieving a body mass index (BMI, calculated as weight in kilograms
      divided by height in meters squared) of less than 30 is an important goal of
      bariatric surgery, given the increased risk for weight-related morbidity and
      mortality with a BMI above this threshold. Objective: To identify predictors for
      achieving a BMI of less than 30 after bariatric surgery. Design, Setting, and
      Participants: This retrospective study used data from the Michigan Bariatric
      Surgery Collaborative, a statewide quality improvement collaborative that uses a
      prospectively gathered clinical data registry. A total of 27 320 adults
      undergoing primary bariatric surgery between June 2006 and May 2015 at teaching
      and nonteaching hospitals in Michigan were included. Exposure: Bariatric surgery.
      Main Outcomes and Measures: Logistic regression was used to identify predictors
      for achieving a BMI of less than 30 at 1 year after surgery. Secondary outcome
      measures included 30-day postoperative complications and 1-year self-reported
      comorbidity remission. Results: A total of 9713 patients (36%; mean [SD] age,
      46.9 [11.3] years; 16.6% male) achieved a BMI of less than 30 at 1 year after
      bariatric surgery. A significant predictor for achieving this goal was a
      preoperative BMI of less than 40 (odds ratio [OR], 12.88; 95% CI, 11.71-14.16; P
      < .001). Patients who had a sleeve gastrectomy, gastric bypass, or duodenal
      switch were more likely to achieve a BMI of less than 30 compared with those who
      underwent adjustable gastric banding (OR, 8.37 [95% CI, 7.44-9.43]; OR, 21.43
      [95% CI, 18.98-24.19]; and OR, 82.93 [95% CI, 59.78-115.03], respectively; P <
      .001). Only 8.5% of patients with a BMI greater than 50 achieved a BMI of less
      than 30 after bariatric surgery. Patients who achieved a BMI of less than 30 had
      significantly higher reported rates of medication discontinuation for
      hyperlipidemia (60.7% vs 43.2%, P < .001), diabetes (insulin: 67.7% vs 50.0%, P <
      .001; oral medications: 78.5% vs 64.3%, P < .001), and hypertension (54.7% vs
      34.6%, P < .001), as well as a significantly higher rate of sleep apnea remission
      (72.5% vs 49.3%, P < .001) and higher satisfaction rate (92.8% vs 78.0%, P <
      .001) compared with patients who did not. Conclusions and Relevance: Patients
      with a preoperative BMI of less than 40 are more likely to achieve a BMI of less
      than 30 after bariatric surgery and are more likely to experience comorbidity
      remission. Policies and practice patterns that delay bariatric surgery until the
      BMI is 50 or greater can result in significantly inferior outcomes.

PMID- 28746724
TI  - Undertriage of Firearm-Related Injuries Not Actually Assessed.

PMID- 28746725
TI  - An Acceptability Trial of Desiccated Beef Liver and Meat Powder as Potential
      Fortifiers of Complementary Diets of Young Children in Indonesia.
AB  - The addition of desiccated beef liver to infant and young child complementary
      foods can be used to overcome nutrient deficits, however its acceptability is
      unknown. We conducted a series of studies to test the acceptability of
      complementary foods fortified with either powdered beef liver, beef meat, beef
      liver + meat or placebo among 96 Indonesian children aged 12 to 23 mo. This was
      achieved by determining liking of a single test food with added study powder,
      followed by a 2-wk home trial and focus group discussions to assess liking during
      repeated consumption of the study powders added to daily meals. The test food
      with added beef powders were well liked by mothers, with liking scores never
      falling below neutral on a 7-point scale. After home use, mothers reported that
      their children moderately liked their meals with added powder, with scores
      ranging between 3.3 and 3.5 on a 5-point scale. With the exception of lower
      liking for the combination beef liver + meat powder, there were no detectable
      differences in mothers' overall perception of child's liking between the placebo
      and any of the study powders. The low disappearance rate of the study powders
      during the home trial was a concern, with mothers reporting a strong smell and
      fishy odor as the major reason why children did not like their meals.
      Nonetheless, mothers declared they would continue using the powder on account of
      the nutritional value and perceived health benefits. Strategies are underway to
      minimize the level of fishy odor in the beef liver powder.

PMID- 28746726
TI  - Cauda equina repair in the rat: Part 3. Axonal regeneration across Schwann cell
      Seeded collagen foam.
AB  - INTRODUCTION: Treatments for patients with cauda equina injury are limited.
      METHODS: In this study, we first used retrograde labeling to determine the
      relative contributions of cauda equina motor neurons to intrinsic and extrinsic
      rat tail muscles. Next, we transected cauda equina ventral roots and proceeded to
      bridge the proximal and distal stumps with either a type I collagen scaffold
      coated in laminin (CL) or a collagen-laminin scaffold that was also seeded with
      Schwann cells (CLSC). Regeneration was assessed by way of serial retrograde
      labeling. RESULTS: After accounting for the axonal contributions to intrinsic vs.
      extrinsic tail muscles, we noted a higher degree of double labeling in the CLSC
      group (58.0 +/- 39.6%) as compared with the CL group (27.8 +/- 16.0%; P = 0.02),
      but not the control group (33.5 +/- 18.2%; P = 0.10). DISCUSSION: Our findings
      demonstrate the feasibility of using CLSCs in cauda equina injury repair. Muscle
      Nerve 57: E78-E84, 2018.

PMID- 28746727
TI  - Idiopathic male infertility related to periodontal and caries status.
AB  - OBJECTIVES: This study was undertaken to evaluate the possible correlation
      between the periodontal and dental status and sperm pathology in idiopathic male
      infertility. METHODS: The periodontal and caries status and semen quality of 199
      men presented with unexplained male infertility were examined. Periodontal and
      dental factors were analysed by sperm pathology categories. RESULTS: A total of
      106 men had normal sperm parameters, whereas 93 men had some type of
      spermpathology; 27.95% had oligozoospermia, 23.65% asthenozoospermia, 16.12%
      cryptozoospermia, 32.25% combined oligo-asthenozoospermia. Poor periodontal
      status was found in about half of the study group (45.7%). The DMFT index was not
      a significantly higher in any of the spermpathology groups. The odds ratio of
      calculus, bleeding on probing (BOP) and BOP at >=50% of the teeth were
      significantly higher in the combined group (AOR = 1.04, AOR = 1.13, AOR = 4.92,
      respectively) in multivariate analyses compared to those in the normozoospermia
      group. Gingival bleeding in the history and urban residency were the only
      predictors for pathospermia shown by the logistic regression model (AORs were
      1.82 and 2.26, respectively). CONCLUSIONS: Some features of poor periodontal
      status, as gingival bleeding in the history, presence of calculus and BOP, were
      associated with oligo+asthenozoospermia in men with idiopathic infertility.

PMID- 28746728
TI  - Analysis of the Electronic Structure of the Special Pair of a Bacterial
      Photosynthetic Reaction Center by 13 C Photochemically Induced Dynamic Nuclear
      Polarization Magic-Angle Spinning NMR Using a Double-Quantum Axis.
AB  - The origin of the functional symmetry break in bacterial photosynthesis
      challenges since several decades. Although structurally very similar, the two
      branches of cofactors in the reaction center (RC) protein complex act very
      differently. Upon photochemical excitation, an electron is transported along one
      branch, while the other remains inactive. Photochemically induced dynamic nuclear
      polarization (photo-CIDNP) magic-angle spinning (MAS) 13 C NMR revealed that the
      two bacteriochlorophyll cofactors forming the "Special Pair" donor dimer are
      already well distinguished in the electronic ground state. These previous studies
      are relying solely on 13 C-13 C correlation experiments as radio-frequency-driven
      recoupling (RFDR) and dipolar-assisted rotational resonance (DARR). Obviously,
      the chemical-shift assignment is difficult in a dimer of tetrapyrrole
      macrocycles, having eight pyrrole rings of similar chemical shifts. To overcome
      this problem, an INADEQUATE type of experiment using a POST C7 symmetry-based
      approach is applied to selectively isotope-labeled bacterial RC of Rhodobacter
      (R.) sphaeroides wild type (WT). We, therefore, were able to distinguish
      unresolved sites of the macromolecular dimer. The obtained chemical-shift pattern
      is in-line with a concentric assembly of negative charge within the common center
      of the Special Pair supermolecule in the electronic ground state.

PMID- 28746729
TI  - Pleurotus sajor-caju can be used to synthesize silver nanoparticles with
      antifungal activity against Candida albicans.
AB  - BACKGROUND: Green synthesis of silver nanoparticles (AgNPs) has become widely
      practiced worldwide. In this study, AgNPs were synthesized using a hot-water
      extract of the edible mushroom Pleurotus sajor-caju. The product, PSC-AgNPs, was
      characterized by using UV-visible spectra, dynamic light scattering analysis,
      transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier
      transform infrared (FTIR) spectrometry. To assess its antifungal activity against
      Candida albicans, gene transcription and protein expression analyses were
      conducted for CaICL1 and its product, ICL, using real-time quantitative
      polymerase chain reaction and western blot, respectively. RESULTS: PSC-AgNPs with
      an average particle size of 11.68 nm inhibited the growth of the pathogenic yeast
      C. albicans. Values for minimum inhibitory concentration and minimum fungicidal
      concentration were 250 and 500 mg L-1 , respectively. TEM images revealed that
      the average particle size of PSC-AgNPs was 16.8 nm, with the values for zeta
      potential and the polydispersity index being -8.54 mV and 0.137, respectively.
      XRD and FTIR spectra showed PSC-AgNPs to have a face-centered cubic crystalline
      structure. The polysaccharides and amino acid residues present in P. sajor-caju
      extract were found to be involved in reducing Ag+ to AgNP. Both CaICL1
      transcription and ICL protein expression were found to be suppressed in the cells
      treated with PSC-AgNPs as compared with the control. CONCLUSION: Our PSC-AgNP
      preparation makes for a promising antifungal agent that can downregulate
      isocitrate lyase. (c) 2017 Society of Chemical Industry.

PMID- 28746730
TI  - Fine needle aspiration of abdominal organs: a review of current recommendations
      for achieving a diagnostic sample.
AB  - With the improved accessibility to ultrasound, fine needle aspiration of
      abdominal organs is now performed frequently in many veterinary practices.
      Despite this, there are many 'unknowns' as to the best method to produce a high
      quality sample. This report begins by highlighting recent literature on the risks
      and benefits of abdominal fine needle aspiration. It follows with recommendations
      about the equipment and method best suited to the procedure, including needle and
      syringe size and aspiration versus non-aspiration techniques. Various smear
      preparations and laboratory submission requirements are also discussed. The final
      aspect of the review more specifically discusses fine needle aspiration of
      specific abdominal organs: the liver, kidney, spleen, pancreas, urinary bladder,
      prostate and abdominal lymph nodes.

PMID- 28746731
TI  - Towards Improved Oligonucleotide Therapeutics Through Faster Target Binding
      Kinetics.
AB  - When used as inhibitors of gene expression in vivo, oligonucleotides require
      modification of their structures to boost their binding affinity for
      complementary target RNAs. To date, hundreds of modifications have been designed
      and tested but few have proven to be useful. Among those investigated are mono-
      and polyamino-groups. These are positively charged at physiological pH and have
      been appended to oligonucleotides in an effort to reduce electrostatic repulsion
      during hybridization to RNAs, but have generally shown relatively minor benefits
      to binding. We conjugated spermine to uracils in oligonucleotides via a triazole
      linker so that the polyamine fits in the major groove of a subsequently formed
      RNA-duplex. The modifications produced large increases in target-binding affinity
      of the oligonucleotides. Using surface plasmon resonance-based assays, we showed
      that the increases derived mainly from faster annealing (kon ). We propose that
      the spermine fragments play a similar role to that of natural polyamines during
      oligonucleotide-target interactions in cells, and may be advantageous for
      oligonucleotides that operate catalytic mechanisms.

PMID- 28746732
TI  - Short-term and long-term clinical outcomes of uncommon types of invasive breast
      cancer.
AB  - AIMS: Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are
      predominant and well-documented types of invasive breast cancer (IBC). We
      investigated the clinical outcomes of other types of IBC (i.e. uncommon IBC),
      which collectively account for Sigma20% of all IBC cases, as these are largely
      unknown. METHODS AND RESULTS: We identified all IBC cases diagnosed in 2004-2006
      (n = 159 293) and 2010-2011 (n = 118 822) from the Surveillance, Epidemiology and
      End Results (SEER) database. Uncommon IBCs included mixed IDC and ILC (MDLC), IDC
      mixed with other types of carcinoma, ILC mixed with other types of carcinoma, and
      other-type breast cancers (OCs). We estimated overall survival (OS) and cancer
      specific survival in multivariate regression models. As compared with IDC, MDLC
      was associated with an increased OS [adjusted hazard ratio (aHR) = 0.92, P <
      0.001 at Sigma10 years of follow-up; aHR = 0.88, P = 0.01 at Sigma4 years of
      follow-up], whereas OCs were associated with a decreased OS (aHR = 1.06, P =
      0.005 at Sigma10 years of follow-up; aHR = 1.23, P < 0.001 at Sigma4 years of
      follow-up). Women with other uncommon IBCs had an OS similar to those with IDC.
      Heterogeneity in survival was observed for some subtypes of OC, with better OS
      for women with MDLC and tubular carcinoma. Radiotherapy extended OS for all types
      of IBC in older women (>=50 years). For younger women (<50 years), radiotherapy
      improved OS in women with IDC, but not in those with ILC or uncommon IBC.
      Radiotherapy did not change cancer-specific survival of younger women with any
      IBC. CONCLUSIONS: Uncommon IBCs have distinct patterns of prognosis and survival.
      The effectiveness of radiotherapy in women with uncommon IBC may differ by age.
      The underlying mechanisms warrant further studies.

PMID- 28746733
TI  - Mothers with substance addictions show reduced reward responses when viewing
      their own infant's face.
AB  - Maternal addiction constitutes a major public health problem affecting children,
      with high rates of abuse, neglect, and foster care placement. However, little is
      known about the ways in which substance addiction alters brain function related
      to maternal behavior. Prior studies have shown that infant face cues activate
      similar dopamine-associated brain reward regions to substances of abuse. Here, we
      report on a functional MRI study documenting that mothers with addictions
      demonstrate reduced activation of reward regions when shown reward-related cues
      of their own infants. Thirty-six mothers receiving inpatient treatment for
      substance addiction were scanned at 6 months postpartum, while viewing happy and
      sad face images of their own infant compared to those of a matched unknown
      infant. When viewing happy face images of their own infant, mothers with
      addictions showed a striking pattern of decreased activation in dopamine- and
      oxytocin-innervated brain regions, including the hypothalamus, ventral striatum,
      and ventromedial prefrontal cortex-regions in which increased activation has
      previously been observed in mothers without addictions. Our results are the first
      to demonstrate that mothers with addictions show reduced activation in key reward
      regions of the brain in response to their own infant's face cues. Hum Brain Mapp
      38:5421-5439, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28746734
TI  - Spatial evaluation of Indonesia's 2015 fire-affected area and estimated carbon
      emissions using Sentinel-1.
AB  - Fires raged once again across Indonesia in the latter half of 2015, creating a
      state of emergency due to poisonous smoke and haze across Southeast Asia as well
      as incurring great financial costs to the government. A strong El Nino-Southern
      Oscillation (ENSO) led to drought in many parts of Indonesia, resulting in
      elevated fire occurrence comparable with the previous catastrophic event in
      1997/1998. Synthetic Aperture Radar (SAR) data promise to provide improved
      detection of land use and land cover changes in the tropics as compared to
      methodologies dependent upon cloud- and haze-free images. This study presents the
      first spatially explicit estimates of burned area across Sumatra, Kalimantan, and
      West Papua based on high-resolution Sentinel-1A SAR imagery. Here, we show that
      4,604,569 hectares (ha) were burned during the 2015 fire season (overall accuracy
      84%), and compare this with other existing operational burned area products
      (MCD64, GFED4.0, GFED4.1s). Intersection of burned area with fine-scale land
      cover and peat layer maps indicates that 0.89 gigatons carbon dioxide equivalents
      (Gt CO2 e) were released through the fire event. This result is compared to other
      estimates based on nonspatially explicit thermal anomaly measurements or
      atmospheric monitoring. Using freely available SAR C-band data from the Sentinel
      mission, we argue that the presented methodology is able to quickly and precisely
      detect burned areas, supporting improvement in fire control management as well as
      enhancing accuracy of emissions estimation.

PMID- 28746736
TI  - Defensive repertoire of Drosophila larvae in response to toxic fungi.
AB  - Chemical warfare including insecticidal secondary metabolites is a well-known
      strategy for environmental microbes to monopolize a food source. Insects in turn
      have evolved behavioural and physiological defences to eradicate or neutralize
      the harmful microorganisms. We studied the defensive repertoire of insects in
      this interference competition by combining behavioural and developmental assays
      with whole-transcriptome time-series analysis. Confrontation with the toxic
      filamentous fungus Aspergillus nidulans severely reduced the survival of
      Drosophila melanogaster larvae. Nonetheless, the larvae did not behaviourally
      avoid the fungus, but aggregated at it. Confrontation with fungi strongly
      affected larval gene expression, including many genes involved in detoxification
      (e.g., CYP, GST and UGT genes) and the formation of the insect cuticle (e.g.,
      Tweedle genes). The most strongly upregulated genes were several members of the
      insect-specific gene family Osiris, and CHK-kinase-like domains were over
      represented. Immune responses were not activated, reflecting the competitive
      rather than pathogenic nature of the antagonistic interaction. While internal
      microbes are widely acknowledged as important, our study emphasizes the
      underappreciated role of environmental microbes as fierce competitors.

PMID- 28746735
TI  - Early transcriptional response pathways in Daphnia magna are coordinated in
      networks of crustacean-specific genes.
AB  - Natural habitats are exposed to an increasing number of environmental stressors
      that cause important ecological consequences. However, the multifarious nature of
      environmental change, the strength and the relative timing of each stressor
      largely limit our understanding of biological responses to environmental change.
      In particular, early response to unpredictable environmental change, critical to
      survival and fitness in later life stages, is largely uncharacterized. Here, we
      characterize the early transcriptional response of the keystone species Daphnia
      magna to twelve environmental perturbations, including biotic and abiotic
      stressors. We first perform a differential expression analysis aimed at
      identifying differential regulation of individual genes in response to stress.
      This preliminary analysis revealed that a few individual genes were responsive to
      environmental perturbations and they were modulated in a stressor and genotype
      specific manner. Given the limited number of differentially regulated genes, we
      were unable to identify pathways involved in stress response. Hence, to gain a
      better understanding of the genetic and functional foundation of tolerance to
      multiple environmental stressors, we leveraged the correlative nature of networks
      and performed a weighted gene co-expression network analysis. We discovered that
      approximately one-third of the Daphnia genes, enriched for metabolism, cell
      signalling and general stress response, drives transcriptional early response to
      environmental stress and it is shared among genetic backgrounds. This initial
      response is followed by a genotype- and/or condition-specific transcriptional
      response with a strong genotype-by-environment interaction. Intriguingly,
      genotype- and condition-specific transcriptional response is found in genes not
      conserved beyond crustaceans, suggesting niche-specific adaptation.

PMID- 28746737
TI  - Divergent expression of cytokinin biosynthesis, signaling and catabolism genes
      underlying differences in feeding sites induced by cyst and root-knot nematodes.
AB  - Cyst and root-knot nematodes are obligate parasites of economic importance with a
      remarkable ability to reprogram root cells into unique metabolically active
      feeding sites. Previous studies have suggested a role for cytokinin in feeding
      site formation induced by these two types of nematodes, but the mechanistic
      details have not yet been described. Using Arabidopsis as a host plant species,
      we conducted a comparative analysis of cytokinin genes in response to the beet
      cyst nematode (BCN), Heterodera schachtii, and the root-knot nematode (RKN),
      Meloidogyne incognita. We identified distinct differences in the expression of
      cytokinin biosynthesis, catabolism and signaling genes in response to infection
      by BCN and RKN, suggesting differential manipulation of the cytokinin pathway by
      these two nematode species. Furthermore, we evaluated Arabidopsis histidine
      kinase receptor mutant lines ahk2/3, ahk2/4 and ahk3/4 in response to RKN
      infection. Similar to our previous studies with BCN, these lines were
      significantly less susceptible to RKN without compromising nematode penetration,
      suggesting a requirement of cytokinin signaling in RKN feeding site formation.
      Moreover, an analysis of ahk double mutants using CycB1;1:GUS/ahk introgressed
      lines revealed contrasting differences in the cytokinin receptors mediating cell
      cycle activation in feeding sites induced by BCN and RKN.

PMID- 28746738
TI  - An exploratory trial of a health education programme to promote healthy
      lifestyles through social and emotional competence in young children: Study
      protocol.
AB  - AIM: To implement and evaluate a health education programme based on the
      development of social and emotional competence in young children. BACKGROUND:
      Children's social and emotional skills play a key role in the adoption and
      maintenance of their lifestyles. Currently, a more comprehensive perspective
      dealing with these aspects is needed to promote healthy habits in children and
      develop effective health education programmes. DESIGN: An exploratory randomized
      controlled trial. METHODS: A convenience sample of 30 children (5 and 6 years
      old) will be recruited from a public school in Spain, with 15 participants in the
      experimental group and 15 in the control group. Participants in the experimental
      group will receive the first unit of the programme, consisting of developing
      emotional knowledge skills around daily health habits (eating, hygiene, sleep and
      physical exercise) using different game-based dynamics and an emotional diary,
      while those in the control group will continue with their usual school routine.
      Outcome measures include emotional knowledge ability, basic social skills and
      children's health profile. The perceived impact of the intervention by parents,
      acceptability (by parents and children) and feasibility of the programme will be
      also assessed. Data will be collected at baseline, postintervention and at 7
      month follow-up. DISCUSSION: This study offers an innovative intervention aimed
      at improving children's healthy lifestyles from a holistic perspective by
      addressing social and emotional competence as one of the most influential aspects
      of children's development. This exploratory trial is an essential step to explore
      crucial aspects of the full-scale clinical trial.

PMID- 28746739
TI  - Characterization and Influence of Green Synthesis of Nano-Sized Zinc Complex with
      5-Aminolevulinic Acid on Bioactive Compounds of Aniseed.
AB  - A new water soluble zinc-aminolevulinic acid nano complex (n[Zn(ALA)2 ]), which
      was characterized by TEM, IR, and EDX spectra, has been prepared via sonochemical
      method under green conditions in water. In the current study, the effectiveness
      of foliar Zn amendment using synthetic Zn-ALA nano complex, as a new introduced
      Zn-fertilizer here, was evaluated. As the model plant, Pimpinella anisum, the
      most valuable spice and medicinal plant grown in warm regions, was used. By using
      zinc nano complex, further twenty compounds were obtained in the essential oil of
      anise plants. Application of 0.2% (w/v) Zn-ALA nano complex increased the levels
      of (E)-anethole, beta-bisabolene, germacrene D, methyl chavicol, and alpha
      zingiberene in the essential oil. Nano Zn complex at the rate of 0.2% induced
      considerable high phenolic compounds and zinc content of shoots and seeds.
      Chlorogenic acid had the highest level between four detected phenolic compounds.
      The maximum antioxidant activity was monitored through the application of Zn nano
      complex. According to the results, nanoscale nutrients can be provided with
      further decreased doses for medicinal plants. Using Zn-ALA nano complex is a new
      and efficient method to improve the pharmaceutical and food properties of anise
      plants.

PMID- 28746741
TI  - Rigorous field experiments are essential to understand the genuine severity of
      light pollution and to identify possible solutions.

PMID- 28746740
TI  - CCR6 promotes steady-state mononuclear phagocyte association with the intestinal
      epithelium, imprinting and immune surveillance.
AB  - The intestinal lamina propria (LP) contains antigen-presenting cells with
      features of dendritic cells and macrophages, collectively referred to as
      mononuclear phagocytes (MNPs). Association of MNPs with the epithelium is thought
      to play an important role in multiple facets of intestinal immunity including
      imprinting MNPs with the ability to induce IgA production, inducing the
      expression of gut homing molecules on T cells, facilitating the capture of
      luminal antigens and microbes, and subsequent immune responses in the mesenteric
      lymph node (MLN). However, the factors promoting this process in the steady state
      are largely unknown, and in vivo models to test and confirm the importance of LP
      MNP association with the epithelium for these outcomes are unexplored. Evaluation
      of epithelial expression of chemoattractants in mice where MNP-epithelial
      associations were impaired suggested CCL20 as a candidate promoting epithelial
      association. Expression of CCR6, the only known receptor for CCL20, was required
      for MNPs to associate with the epithelium. LP-MNPs from CCR6-/- mice did not
      display defects in acquiring antigen and stimulating T-cell responses in ex vivo
      assays or in responses to antigen administered systemically. However, LP-MNPs
      from CCR6-deficient mice were impaired at acquiring luminal and epithelial
      antigens, inducing IgA production in B cells, inducing immune responses in the
      MLN, and capturing and trafficking luminal commensal bacteria to the MLN. These
      findings identify a crucial role for CCR6 in promoting LP-MNPs to associate with
      the intestinal epithelium in the steady state to perform multiple functions
      promoting gut immune homeostasis.

PMID- 28746742
TI  - Forging Fluorine-Containing Quaternary Stereocenters by a Light-Driven
      Organocatalytic Aldol Desymmetrization Process.
AB  - Reported herein is a light-triggered organocatalytic strategy for the
      desymmetrization of achiral 2-fluoro-substituted cyclopentane-1,3-diketones. The
      chemistry is based on an intermolecular aldol reaction of photochemically
      generated hydroxy-o-quinodimethanes and simultaneously forges two adjacent fully
      substituted carbon stereocenters, with one bearing a stereogenic carbon-fluorine
      unit. The method uses readily available substrates, a simple chiral
      organocatalyst, and mild reaction conditions to afford an array of highly
      functionalized chiral 2-fluoro-3-hydroxycyclopentanones.

PMID- 28746743
TI  - Incretin concept revised: The origin of the insulinotropic function of glucagon
      like peptide-1 - the gut, the islets or both?
AB  - Incretins comprise a pair of gut hormones, glucose-dependent insulinotropic
      polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which are secreted in
      response to food ingestion and enhance glucose-dependent insulin secretion from
      pancreatic beta-cells. Immediately after secretion, GLP-1 is degraded by
      dipeptidyl peptidase-4 more rapidly than GIP, and circulating levels of
      biologically intact GLP-1 are substantially lower than those of biologically
      intact GIP. Therefore, there has been a debate on how the gut-derived GLP-1
      exerts insulinotropic actions. Recent publications have revealed two novel
      mechanisms by which GLP-1 exerts insulinotropic actions: (i) the gut-derived GLP
      1 activates receptors expressed in nodose ganglions, thereby potentiating glucose
      dependent insulin secretion through the vagus nerves; and (ii) the pancreatic
      alpha-cell-derived GLP-1 activates receptors expressed in beta-cells in a
      paracrine manner. While the relative contributions of the two mechanisms under
      normal and pathological conditions remain unknown and mechanisms regulating GLP-1
      secretion from alpha-cells need to be investigated, the available data strongly
      indicate that the effects of GLP-1 on insulin secretion are far more complex than
      previously believed, and the classical incretin concept regarding GLP-1 should be
      revised.

PMID- 28746744
TI  - Enzyme-Responsive LipoCEST Agents: Assessment of MMP-2 Activity by Measuring the
      Intra-liposomal Water 1 H NMR Shift.
AB  - Mobile proton-containing solutes can be detected by MRI by the chemical exchange
      saturation transfer (CEST) method. CEST sensitivity is dramatically enhanced by
      using, as exchanging protons, the water molecules confined inside liposomes,
      shifted by a paramagnetic shift reagent. The chemical shift of the intraliposomal
      water resonance (deltaIL ) is affected by the overall shape of the supramolecular
      system. deltaIL of a spherical LipoCEST acts as a sensitive reporter of the
      distribution of streptavidin proteins anchored at the liposome surface by
      biotinylated phospholipids. This finding prompted the design of a MMP-2
      responsive LipoCEST agent as the streptavidin moieties can be released from the
      liposome surfaces when a properly tailored enzyme-cleavable peptide is inserted
      on the phospholipids before the terminal biotin residues. deltaIL reports on the
      overall changes in the supramolecular architecture associated to the cleavage
      carried out by MMP-2.

PMID- 28746745
TI  - Apical stress distribution under vertical compaction of gutta-percha and occlusal
      loads in canals with varying apical sizes: a three-dimensional finite element
      analysis.
AB  - AIM: To investigate and compare the effects of two apical canal instrumentation
      protocols on apical stress distribution at the root apex under vertical
      compaction of gutta-percha and occlusal loads using finite element analysis.
      METHODOLOGY: Three finite element analysis models of a mandibular first premolar
      were reconstructed: an original canal model, a size 35, .04 taper apical canal
      enlargement model and a Lightspeed size 60 apical canal enlargement model. A 15 N
      compaction force was applied vertically to the gutta-percha 5 mm from the apex. A
      175 N occlusal load in two directions (vertical and 45 degrees  to the
      longitudinal axis of the tooth) was simulated. Stresses in the apical 2 mm of the
      root were calculated and compared among the three models. RESULTS: Under vertical
      compaction, stresses in the apical canal instrumented by Lightspeed size 60
      (maximal 3.3 MPa) were higher than that of the size 35, .04 taper model (maximal
      1.3 MPa). In the case of the two occlusal forces, the Lightspeed size 60 apical
      enlargement was associated with the greatest stress distribution in the apical
      region. The greatest stress and the most obvious stress difference between the
      models appeared at the tip of the root when occlusal and vertical compaction
      loads were applied. CONCLUSIONS: Apical enlargement caused stress distribution
      changes in the apical region of roots. The larger apical size led to higher
      stress concentration at the root apex.

PMID- 28746746
TI  - Outcomes of patients with metastatic phaeochromocytoma and paraganglioma: A
      systematic review and meta-analysis.
AB  - OBJECTIVE: The outcomes of patients with metastatic phaeochromocytoma (PHEO) and
      paraganglioma (PGL) are unclear. We performed a systematic review and meta
      analysis of baseline characteristics and mortality rates of patients with
      metastatic PHEO and PGL (PPGL). DESIGN: 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, Scopus, Web of
      Science, and references of key articles were searched from inception to 2016.
      PATIENTS: Studies comprised >=20 patients with metastatic PPGL and reported
      baseline characteristics and follow-up data. MEASUREMENTS: Reviewers extracted
      standardized data and assessed risk of bias using a modified Newcastle-Ottawa
      tool. Random-effects meta-analysis was used to pool event rates across studies.
      RESULTS: Twenty retrospective noncomparative studies reported on 1338 patients
      with metastatic PHEO (685/1296, 52.9%) and PGL (611/1296, 47.1%), diagnosed at a
      mean age of 43.9 +/- 5.2 years. Mean follow-up was 6.3 +/- 3.2 years. Of 532
      patients with reported data, 40.4% had synchronous metastases. Five-year (7
      studies, n = 738) and 10-year (2 studies, n = 55) mortality rates for patients
      with metastatic PPGL were 37% (95% CI, 24%-51%) and 29% (95% CI, 17%-42%),
      respectively. Higher mortality was associated with male sex (RR 1.50; 95% CI,
      1.11-2.02) and synchronous metastases (RR 2.43; 95% CI, 1.01-5.85). CONCLUSIONS:
      Available low-quality evidence from heterogeneous studies suggests low mortality
      rates of patients with metastatic PPGL. Male sex and synchronous metastases
      correlated with increased mortality. The outcomes of patients with metastatic
      PPGL have been inadequately assessed, indicating the need for carefully planned
      prospective studies.

PMID- 28746748
TI  - Validation and description of Symbiodinium microadriaticum, the type species of
      Symbiodinium (Dinophyta).
AB  - It has been 55 years since Hugo Freudenthal described Symbiodinium
      microadriaticum (Dinophyceae), the type species of this large and important
      dinoflagellate genus found commonly in mutualistic symbiosis with cnidarians,
      other invertebrates, and certain protists. However, no type specimen was
      designated by Freudenthal, thus S. microadriaticum was invalid, as was
      Symbiodinium and every species subsequently assigned to the genus. The original
      culture was lost, but since 1979, a different culture, CCMP2464/rt-061, had been
      considered to represent S. microadriaticum. From this culture, a preserved
      specimen is herein designated the holotype of S. microadriaticum, validating the
      binomial and Symbiodinium. All binary designations previously considered to
      belong in Symbiodinium also are validated herein.

PMID- 28746747
TI  - Association of Posttraumatic Stress Disorder With rs2267735 in the ADCYAP1R1
      Gene: A Meta-Analysis.
AB  - Recent studies point to the potential role of the (pituitary) adenylate cyclase
      activating polypeptide receptor 1 (ADCYAP1R1) gene, which has been implicated in
      stress response, in posttraumatic stress disorder (PTSD). Multiple genetic
      association studies have examined potential PTSD risk related to this gene, with
      mixed results. We conducted a meta-analysis of rs2267735 in ADCYAP1R1 in PTSD. A
      literature search was conducted using PubMed and PsycINFO, resulting in nine
      studies that met criteria for inclusion in analysis. Biostat's Comprehensive Meta
      Analysis was used to conduct the main meta-analysis on the combined sex sample,
      as well as two subanalyses examining effects separately in female and male
      participants. Results indicated that the C allele of rs2267735 conferred
      significant risk for PTSD in the combined sex data, OR = 1.210, 95% CI [1.007,
      1.454], p = .042, and in the subsample of women and girls, OR = 1.328, 95% CI
      [1.026, 1.719], p = .031; but not in the subsample of men and boys, OR = 0.964,
      95% CI [0.733, 1.269], p = .796. These results provide evidence for an
      association between ADCYAP1R1 and PTSD and indicate that there may indeed be sex
      differences. Implications of these findings, including the role of rs2267735 as
      one modulator of the stress system, are discussed.

PMID- 28746749
TI  - High-throughput Transcriptome Sequencing Reveals the Role of Anthocyanin
      Metabolism in Begonia semperflorens Under High Light Stress.
AB  - Begonia semperflorens is an ornamental perennial herb. The leaves of B.
      semperflorens turn red under increased light, which increases the ornamental
      value of the plant. The color of the leaves is determined by anthocyanin
      metabolism. In B. semperflorens leaves, anthocyanin metabolism is sensitive to
      external environmental conditions such as temperature, light and hormone levels.
      To explore this process in detail and to assess gene expression under high light
      stress, transcriptome analysis was performed by RNA sequencing using the
      sequencing-by-synthesis method. A total of 83 699 unigenes were isolated, and 51
      754 unigenes were annotated using the NR, Swiss-Prot, KEGG, COG, KOG, GO and Pfam
      databases. Furthermore, many of the differentially expressed genes were related
      to factors associated with anthocyanin metabolism, which influences the
      expression of leaf color.

PMID- 28746750
TI  - The emotional impact of errors or adverse events on healthcare providers in the
      NICU: The protective role of coworker support.
AB  - AIMS: To examine the impact of errors or adverse events on emotional distress and
      professional quality of life in healthcare providers in the neonatal intensive
      care unit, and the moderating role of coworker support. BACKGROUND: Errors or
      adverse events can result in negative outcomes for healthcare providers. However,
      the role of coworker support in improving emotional and professional outcomes has
      not been examined. DESIGN: A cross-sectional online survey from a quality
      improvement initiative to train peer supporters in a neonatal intensive care
      unit. METHODS: During 2015, 463 healthcare providers in a neonatal intensive care
      unit completed a survey assessing their experiences with an error or adverse
      event, anxiety, depression, professional quality of life and coworker support.
      RESULTS: Compared with those who did not experience an error or adverse event
      (58%), healthcare providers who observed (23%) or were involved (19%) in an
      incident reported higher levels of anxiety and secondary traumatic stress. Those
      who were involved in an event reported higher levels of depression and burnout.
      Differences between the three groups (no event, observation and involvement) for
      compassion satisfaction were non-significant. Perceived coworker support
      moderated the association between experiencing an event and both anxiety and
      depression. Specifically, experiencing an event was associated with higher levels
      of anxiety and depression when coworkers were perceived as low in supportiveness,
      but not when they were viewed as highly supportive. CONCLUSION: Findings suggest
      that errors or adverse events can have a harmful impact on healthcare providers
      and that coworker support may reduce emotional distress.

PMID- 28746751
TI  - Cancer donor preferences for disposition of their biospecimens after biobank
      closure.
AB  - BACKGROUND: Biobank funding is unstable and biobank administrators are concerned
      about loss of funding and subsequent biobank closure. Nevertheless, only a
      minority of biobanks have policies regarding the distribution or destruction of
      tissue if the biobank were to close. To the authors' knowledge, the current study
      is the first to report on the preferences of oncology biospecimen donors
      regarding the handling of their biospecimens in the event of biobank closure.
      METHODS: A total of 98 biospecimen donors who were diagnosed with cancer at the
      Georgia Cancer Center for Excellence at Grady Memorial Hospital or the Winship
      Cancer Institute were interviewed concerning their preferences for the handling
      of their biospecimens in the event of biobank closure. RESULTS: The majority of
      biospecimen donors who expressed a preference (62 of 83 donors; 75%) wanted their
      biological materials transferred to another biobank, specifically an academic
      bank or a national bank. The most unacceptable options for the handling of tissue
      were transfer to a for-profit/pharmaceutical biobank (39 of 98 donors; 40%) or a
      biobank based outside of the United States (31 of 98 donors; 32%). Nonwhite
      participants were more likely to view the transfer of their tissue to a for
      profit/pharmaceutical tissue bank, international tissue bank, or a national
      tissue bank as unacceptable compared with white participants. CONCLUSIONS:
      According to these biospecimen donors, the most acceptable options for the
      handling of biospecimens after biobank closure were transfer to an academic or
      national bank. The most objectionable options were transfer to a for
      profit/pharmaceutical biobank or a biobank based outside of the United States.
      These findings can be used as the basis for educational interventions directed at
      the public and can inform the policies of biobanks that serve oncology research.
      Cancer 2017;123:4648-4652. (c) 2017 American Cancer Society.

PMID- 28746752
TI  - Immunotherapy for diabetic amyotrophy.
AB  - BACKGROUND: People with diabetes mellitus (DM) sometimes present with acute or
      subacute, progressive, asymmetrical pain and weakness of the proximal lower limb
      muscles. The various names for the condition include diabetic amyotrophy,
      diabetic lumbosacral radiculoplexus neuropathies, diabetic femoral neuropathy or
      Bruns-Garland syndrome. Some studies suggest that diabetic amyotrophy may be an
      immune-mediated inflammatory microvasculitis causing ischaemic damage of the
      nerves. Immunotherapies would therefore be expected to be beneficial. This is the
      second update of a review first published in 2009. OBJECTIVES: To review the
      evidence from randomised trials for the efficacy of any form of immunotherapy in
      the treatment of diabetic amyotrophy. SEARCH METHODS: On 5 September 2016 we
      searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and
      Embase. We also contacted authors of relevant publications and other experts to
      obtain additional references, unpublished trials, and ongoing trials. SELECTION
      CRITERIA: We intended to include all randomised and quasi-randomised trials of
      any immunotherapy in participants with the condition fulfilling all the
      following: diabetes mellitus as defined by internationally recognised criteria;
      acute or subacute onset of pain and lower motor neuron weakness involving
      predominantly the proximal muscles of the lower limbs; weakness that is not
      confined to one nerve or nerve root distribution; and exclusion of other causes
      of lumbosacral radiculopathies and plexopathy. DATA COLLECTION AND ANALYSIS: Two
      authors independently examined all references retrieved by the search to select
      those meeting the inclusion criteria. MAIN RESULTS: We found only one completed
      placebo-controlled trial (N = 75) using intravenous methylprednisolone in
      diabetic amyotrophy (Dyck 2006). The results have not been fully published and
      were not available for analysis. The risk of bias was unclear because there was
      too little information to make a judgement, but we considered the trial at high
      risk of selective reporting. The published abstract did not report adverse
      events. We found no additional trials when the searches were updated in September
      2016. AUTHORS' CONCLUSIONS: There is presently no evidence from randomised trials
      to support a positive or negative effect of any immunotherapy in the treatment in
      diabetic amyotrophy.

PMID- 28746753
TI  - The author's reply "Ultrasonography and cytology as predictors of noninvasive
      follicular thyroid (NIFTP) neoplasm with papillary-like nuclear features:
      importance of the differential diagnosis with the invasive encapsulated
      follicular variant of papillary thyroid cancer".

PMID- 28746754
TI  - Structure and stability of genetic variance-covariance matrices: A Bayesian
      sparse factor analysis of transcriptional variation in the three-spined
      stickleback.
AB  - The genetic variance-covariance matrix (G) is a quantity of central importance in
      evolutionary biology due to its influence on the rate and direction of
      multivariate evolution. However, the predictive power of empirically estimated G
      matrices is limited for two reasons. First, phenotypes are high-dimensional,
      whereas traditional statistical methods are tuned to estimate and analyse low
      dimensional matrices. Second, the stability of G to environmental effects and
      over time remains poorly understood. Using Bayesian sparse factor analysis (BSFG)
      designed to estimate high-dimensional G-matrices, we analysed levels variation
      and covariation in 10,527 expressed genes in a large (n = 563) half-sib breeding
      design of three-spined sticklebacks subject to two temperature treatments. We
      found significant differences in the structure of G between the treatments:
      heritabilities and evolvabilities were higher in the warm than in the low
      temperature treatment, suggesting more and faster opportunity to evolve in warm
      (stressful) conditions. Furthermore, comparison of G and its phenotypic
      equivalent P revealed the latter is a poor substitute of the former. Most
      strikingly, the results suggest that the expected impact of G on evolvability-as
      well as the similarity among G-matrices-may depend strongly on the number of
      traits included into analyses. In our results, the inclusion of only few traits
      in the analyses leads to underestimation in the differences between the G
      matrices and their predicted impacts on evolution. While the results highlight
      the challenges involved in estimating G, they also illustrate that by enabling
      the estimation of large G-matrices, the BSFG method can improve predicted
      evolutionary responses to selection.

PMID- 28746755
TI  - Interaction network of ABA receptors in grey poplar.
AB  - The plant hormone abscisic acid (ABA) is a key player in responses to abiotic
      stress. ABA regulates a plant's water status and mediates drought tolerance by
      controlling stomatal gas exchange, water conductance and differential gene
      expression. ABA is recognized and bound by the Regulatory Component of ABA
      Receptors (RCARs)/PYR1/PYL (Pyrabactin Resistance 1/PYR1-like). Ligand binding
      stabilizes the interaction of RCARs with type 2C protein phosphatases (PP2C),
      which are ABA co-receptors. While the core pathway of ABA signalling has been
      elucidated, the large number of different ABA receptors and co-receptors within a
      plant species generates a complexity of heteromeric receptor complexes that has
      not functionally been resolved in any plant species to date. In this study, we
      characterized ABA receptors and co-receptors of grey poplar (Populus x canescens
      [Ait.] Sm.) and their capacity to regulate ABA responses. We observed a high
      number of regulatory combinations of holo-receptor complexes, but also some
      preferential and selective RCAR-PP2C interactions. Poplar and Arabidopsis ABA
      receptor components revealed a strong structural and functional conservation.
      Heterologous receptor complexes of poplar and Arabidopsis components showed
      functionality in vitro and regulated ABA-responsive gene expression in cells of
      both species. ABA-responsive promoters of Arabidopsis were also active in poplar,
      which was explored to generate poplar reporter lines expressing green fluorescent
      protein in response to ABA. The study presents a detailed analysis of receptor
      complexes of a tree species and shows high conservation of ABA receptor
      components between an annual and a perennial plant.

PMID- 28746756
TI  - De-scenting Extinction: The Promise of De-extinction May Hasten Continuing
      Extinctions.
AB  - Among the most egregious and discouraging problems of conservation is the rapidly
      escalating human-caused species extinction rate. "De-extinction" refers to the
      application of certain cutting-edge techniques for the supposed recovery of lost
      species and gives the impression that scientists, enlightened and empowered by
      the miracles of technology, are coming to the rescue. "De-extinction" is the
      latest example of a long play of language that has given conservation efforts a
      tragically false sense of accomplishment and has worsened the conservation
      crisis. De-extinction is the tip of an intellectual iceberg that sits atop of a
      host of profoundly questionable value systems, expectations, attitudes, and
      priorities that elude and bewitch critical reflection. It gives the impression
      that extinction is reversible and, thus, diminishes the gravity of the human
      annihilation of species. Here, we examine how the language of de-extinction
      influences attitudes, shapes thoughts and imagination, and creates ethical
      blindness. The language developing around "de-extinction" reveals what is in fact
      a profound intellectual crisis at the foundation of conservation. The underlying
      challenge is to find the language that will articulate and inspire the radical
      and indispensable change needed to come to grips with the value of nature.

PMID- 28746757
TI  - De-extinction and Barriers to the Application of New Conservation Tools.
AB  - Decades of globally coordinated work in conservation have failed to slow the loss
      of biodiversity. To do better-even if that means nothing more than failing less
      spectacularly-bolder thinking is necessary. One of the first possible
      conservation applications of synthetic biology to be debated is the use of
      genetic tools to resurrect once-extinct species. Since the currency of
      conservation is biodiversity and the discipline of conservation biology was
      formed around the prevention of species extinctions, the prospect of reversing
      extinctions might have been expected to generate unreserved enthusiasm. But it
      was not universal acclaim that greeted the coming-out party for "de-extinction"
      that was the TEDx conference and accompanying National Geographic feature in
      2013. Why the concern, the skepticism, even the hostility among many
      conservationists about the idea of restoring lost species? And how does this
      professional concern relate to public perception and support for conservation?
      This essay explores the barriers to the acceptance of risky new genomic-based
      conservation tools by considering five key areas and associated questions that
      could be addressed in relation to any new conservation tool. I illustrate these
      using the specific example of de-extinction, and in doing so, I consider whether
      de-extinction would necessarily be the best first point of engagement between
      conservation biology and synthetic biology.

PMID- 28746758
TI  - About The Hastings Center.

PMID- 28746759
TI  - Is De-extinction Special?
AB  - I have been involved with the current interest in de-extinction since early 2012,
      nearly its beginning. I have given a lot of thought to the potential risks and
      benefits of de-extinction. But only recently, after deep immersion in discussions
      around CRISPR-Cas9, the hottest new tool in bioscience since polymerase chain
      reaction, have I thought about a more fundamental question: how, if at all, is de
      extinction special? Are "revived species" just another kind of genetically
      modified organism, raising essentially the same general concerns? I answer, for
      the most part, yes. De-extinction is not (very) special. New biotechnologies are
      giving humans even more power to change the biosphere but more directly, more
      quickly, and more utterly than ever before. De-extinction is just one possible,
      and probably small, use of those technologies. Our attention, for the most part,
      should be on the bigger issues of regulating this power, rather than focusing
      specifically on their application to de-extinction.

PMID- 28746760
TI  - De-extinction and Conservation Genetics in the Anthropocene.
AB  - One interesting feature of de-extinction-particularly with respect to long
      extinct species such as the passenger pigeon, thylacine, and mammoth-is that it
      does not fit neatly into the primary rationales for adopting novel ecosystem
      management and species-conservation technologies and strategies: efficiency and
      necessity. The efficiency rationale is that the new technology or strategy
      enables conservation biologists to do what they already do more effectively. Why
      should researchers embrace novel information technologies? Because they allow
      scientists to better track, monitor, map, aggregate, and analyze species
      behaviors, biological systems, and human-environment interactions. This enables
      better decision-making about how to protect species, which areas to conserve, and
      how to reduce anthropogenic impacts on ecological systems. Many projects in
      conservation genomics are justified in this way. But de-extinction is not a more
      efficient or necessary means to some conservation aim that is already recognized
      as acceptable or important. In fact, because it is focused on reconstituting
      approximations of nonexistent species, rather than maintaining extant ones, the
      social and ethical assessment of de-extinction is not limited to asking whether
      it is a good means. We can ask as well whether de-extinction is a worthwhile
      "conservation" goal in the first place.

PMID- 28746761
TI  - De-extinction and Conservation.
AB  - We are living in what is widely considered the sixth major extinction. Most
      ecologists believe that biodiversity is disappearing at an alarming rate, with up
      to 150 species going extinct per day according to scientists working with the
      United Nations Convention on Biological Diversity. Part of the reason the loss
      signified by biological extinction feels painful is that it seems irremediable.
      These creatures are gone, and there's nothing to be done about it. In recent
      years, however, the possibility has been broached that, just possibly, something
      can be done, in at least some cases. Human ingenuity, a contributing factor in
      the extinction crisis, might achieve their "de-extinction"-in at least some
      cases, and with sometimes significant qualifications about whether the original
      species had been "recreated" and whether it could resume its original place in
      the environment. De-extinction is an entry point into a larger set of questions
      about how biotechnological tools can support, coexist with, or undermine the
      goals of conservation and about the very meaning of conservation. Are we beings
      in control of the world or beings who prosper by accommodating ourselves to webs
      of symbiotic interdependencies? Are we creators or creatures, or both-and if
      both, then how can we achieve the balance between them that might be called
      humility? The interplay of perfecting and accommodating is not unique to human
      beings-perhaps it characterizes all forms of life on Earth-but with humans, these
      modes of being are distinctive, and our technology greatly expands their scale
      and effects. It is such questions that the ten essays in this special report
      explore.

PMID- 28746763
TI  - Reclaiming Hope in Extinction Storytelling.
AB  - Critics often take conservationists to task for delivering a constant barrage of
      bad news without offering a compelling vision of the future. Could recent
      advances in synthetic biology-an optimistic, forward-looking field with a can-do
      attitude-let conservationists develop a new vision and generate some better news?
      Synthetic biology and related gene-editing applications could be used to address
      threats to species. Genetic interventions might also be used in plants to better
      protect biodiversity in U.S. rangelands and forests. One possibility has stood
      out in its ability to capture media attention and the public imagination
      recreating extinct species. And perhaps a de-extinction story could counter the
      seemingly relentless negativity in biodiversity talk. De-extinction proponent
      Stewart Brand writes that resurrecting species could shift the "conservation
      story ... from negative to positive, from constant whining and guilt-tripping to
      high fives and new excitement." So, why do many people in conservation oppose the
      de-extinction narrative? This essay is an inquiry into whether there are
      intrinsic social reactions to these types of conservation solutions that might
      offset their potential benefits. If genetic tools are to be applied to address
      conservation issues in a realistic and responsible way, their broader social
      cultural implications deserve far more attention than they have so far received.

PMID- 28746764
TI  - De-extinction and Taking Control of Earth's "Metabolism".
AB  - In a laboratory on a university campus in Santa Cruz, California, Ben Novak is
      doing everything he can to bring Ectopistes migratorius back from the dead. Using
      techniques now available in genome reading and gene synthesis, he and
      paleogenomicist Beth Shapiro hope that, by 2032, a flock of passenger pigeons ten
      thousand or more strong will have resumed an ecologically significant role in the
      mast forests of the Eastern United States. Novak knows-and the International
      Union for Conservation of Nature (IUCN) affirms-that the challenges involved in
      making de-extinction work are far from solely genetic. Novak is doing an
      ecological risk assessment of passenger pigeon reintroduction to figure out
      whether flocks of the resurrected species would pose any special hazards to
      ecosystems. Ecological harm is one of several worries attending the prospect of
      de-extinction. Among other concerns are the possible harm that individuals born
      through this process might suffer and the possible introduction of disease
      vectors. But I want to step back from these immediate questions and think about
      some conceptual ones that operate in the background. Technology can be a grand
      shaper of cultural norms and expectations, and de-extinction should be looked at
      in relation to a number of emerging technologies. This paper will examine the
      degree to which de-extinction is part of a more widespread restructuring of
      ethical relationships to the surrounding world that are under way at the hands of
      emerging technologies. This restructuring is part of an ongoing shift in how to
      think about conservation in the new epoch of the Anthropocene.

PMID- 28746765
TI  - The Spectacular Garden: Where Might De-extinction Lead?
AB  - The emergence of de-extinction is a study in technological optimism. What has
      already been accomplished in recovering ancient genomes, recreating them, and
      reproducing animals with engineered genomes is amazing but also has a long ways
      to go to achieve "de-extinction" as most people would understand that term.
      Still, with some caveats in place, creating a functional replacement for an
      extinct species may sometimes be doable, and given the right goals, might
      sometimes make sense. The International Union for Conservation of Nature
      guidelines for de-extinction do a reasonable job of keeping the caveats in place
      and clarifying the goals. In fact, given the right caveats about what de
      extinction can accomplish, we should pay a lot of attention to the technology and
      should think carefully about the goals. Not only has the technology been
      advancing, but our environmental standards have been getting looser and more
      flexible, providing less guidance for implementing the technology. The guiding
      ideals for conservation are often explained as a choice between John Muir,
      founder of The Sierra Club, and Gifford Pinchot, who helped create the U.S.
      Forest Service. Muir argued for preserving some places in the world in their
      natural state because of their great value and beauty. Pinchot, by contrast, was
      bluntly utilitarian. He argued for trying to keep some natural places more or
      less undamaged so that we could use them later. There has long been
      dissatisfaction with this choice, and in the last couple of decades, a number of
      prominent voices have proposed a "gardening ethic" as a new standard that
      combines elements of Muir and Pinchot. A gardening ethic is supposed to both
      celebrate the land and declare that it must now be managed. But what would good
      gardening mean when it comes to de-extinction?

PMID- 28746766
TI  - Conservation Genetics, Precision Conservation, and De-extinction.
AB  - It has been estimated that three species on the planet now go extinct every hour
      and that this rate is orders of magnitude higher than the planet has seen in
      previous catastrophic extinction events. We clearly are in the midst of a sixth
      extinction, and this one is different from the previous five. Why? This sixth
      extinction is caused by the activity of a single species-us. If there is any hope
      of ameliorating this extinction, it will entirely be up to us, as the current
      stewards of this planet, to change the course. There are many challenges, though,
      to marshaling this effort. Two primary ones immediately come to mind. The first
      is that we simply haven't found the right biological tools to address this
      crisis. The second is that many humans on this planet don't even admit we have a
      problem. These are two very different problems. The first is primarily
      technological. Only recently has some of the more advanced biologically focused
      technology been available to conservation biology and extinction science. Humans
      are enthralled by cutting-edge technology for the most part, and for the public,
      one of the more exciting possibilities in the realm of conservation biology is
      that some of the more charismatic species that have gone extinct might be
      resurrected through next-generation technologies. While our discussion will
      articulate some weaknesses with the de-extinction approach to conservation
      biology, we suggest that the "sexiness" of the technologies used in de-extinction
      may simultaneously provide a definition of the techniques viable in conservation
      biology and afford a teachable moment.

PMID- 28746767
TI  - The Moral Imagination of De-extinction.
AB  - We live amidst the sixth great extinction of life on Earth, and we live under the
      sign of molecular biology and biotechnology. An ethical maxim that is well-nigh
      universally acknowledged holds that with great power comes great moral
      responsibility. For those who accept the science and embrace the responsibility,
      there are two rather different kinds of moral vision and moral imagination at
      work. Detractors of biotechnology say that we should see ourselves as creaturely
      good citizens of the biotic community, accepting and accommodating what
      evolutionary natural selection has bequeathed to us, warts and all. Boosters of
      biotechnology say that we should see ourselves as its sovereigns, fashioning
      better forms of synthetic life and genetically driving evolution in better ways
      through anthropogenic selection. Faced with biodiversity loss, technology
      boosters, or eco-modernists, tend to respond by upping the ante on technology in
      hopes of increasing the benefits and lessening the impact of human relations with
      nature. The detractors, or eco-communitarians, respond by seeking to restructure
      the relationship between humans and nature by lowering the profile of human power
      so as to hear the voice of nonhuman being and better attune ourselves to it.
      Undergirding both of these moral visions is atonement. As a way of providing
      atonement, however, de-extinction fails.

PMID- 28746768
TI  - De-extinction and the Community of Being.
AB  - Extinction deeply colors the way we think about conservation and the role of
      humans in nature. It is easy to overlook how recently, in fact, it has entered
      our consciousness. Only in the last two centuries has science sought to
      critically study life's origins, development, and diversification. Only in the
      last several generations have we identified and calibrated life's five major
      extinction events and speculated on their causes and effects. And only in recent
      decades have we come to appreciate the still-unfolding fate of life's diversity
      under the increasing influence of humanity. The story of extinction has
      continually changed as this monumental process of interdisciplinary synthesis and
      imagination has unfolded. Geology, paleontology, taxonomy, biogeography, and
      evolutionary biology have allowed us to comprehend the deep temporal and broad
      spatial dynamics of the extinction story. Archaeology, cultural anthropology, and
      environmental and economic history have illuminated the role of humans in
      altering the trajectory of species, landscapes, and ecosystems over the
      millennia. Ecology, genetics, population biology, and conservation biology have
      revealed the more recent patterns in life's vulnerability and resilience. As a
      phenomenon, extinction is as old as life itself. As a story shaping our
      consciousness, values, and intentions, it is still new. And it is uncomfortable.

PMID- 28746769
TI  - Regulation of spindle and kinetochore-associated protein 1 by antitumor miR-10a
      5p in renal cell carcinoma.
AB  - Analysis of our original microRNA (miRNA) expression signature of patients with
      advanced renal cell carcinoma (RCC) showed that microRNA-10a-5p (miR-10a-5p) was
      significantly downregulated in RCC specimens. The aims of the present study were
      to investigate the antitumor roles of miR-10a-5p and the novel cancer networks
      regulated by this miRNA in RCC cells. Downregulation of miR-10a-5p was confirmed
      in RCC tissues and RCC tissues from patients treated with tyrosine kinase
      inhibitors (TKI). Ectopic expression of miR-10a-5p in RCC cell lines (786-O and
      A498 cells) inhibited cancer cell migration and invasion. Spindle and kinetochore
      associated protein 1 (SKA1) was identified as an antitumor miR-10a-5p target by
      genome-based approaches, and direct regulation was validated by luciferase
      reporter assays. Knockdown of SKA1 inhibited cancer cell migration and invasion
      in RCC cells. Overexpression of SKA1 was observed in RCC tissues and TKI-treated
      RCC tissues. Moreover, analysis of The Cancer Genome Atlas database demonstrated
      that low expression of miR-10a-5p and high expression of SKA1 were significantly
      associated with overall survival in patients with RCC. These findings showed that
      downregulation of miR-10a-5p and overexpression of the SKA1 axis were highly
      involved in RCC pathogenesis and resistance to TKI treatment in RCC.

PMID- 28746770
TI  - Unexpected high genetic diversity in small populations suggests maintenance by
      associative overdominance.
AB  - The effective population size (Ne ) is a central factor in determining
      maintenance of genetic variation. The neutral theory predicts that loss of
      variation depends on Ne , with less genetic drift in larger populations. We
      monitored genetic drift in 42 Drosophila melanogaster populations of different
      adult census population sizes (10, 50 or 500) using pooled RAD sequencing. In
      small populations, variation was lost at a substantially lower rate than
      expected. This observation was consistent across two ecological relevant thermal
      regimes, one stable and one with a stressful increase in temperature across
      generations. Estimated ratios between Ne and adult census size were consistently
      higher in small than in larger populations. The finding provides evidence for a
      slower than expected loss of genetic diversity and consequently a higher than
      expected long-term evolutionary potential in small fragmented populations. More
      genetic diversity was retained in areas of low recombination, suggesting that
      associative overdominance, driven by disfavoured homozygosity of recessive
      deleterious alleles, is responsible for the maintenance of genetic diversity in
      smaller populations. Consistent with this hypothesis, the X-chromosome, which is
      largely free of recessive deleterious alleles due to hemizygosity in males, fits
      neutral expectations even in small populations. Our experiments provide
      experimental answers to a range of unexpected patterns in natural populations,
      ranging from variable diversity on X-chromosomes and autosomes to surprisingly
      high levels of nucleotide diversity in small populations.

PMID- 28746771
TI  - Highly Enantioselective Production of Chiral Secondary Alcohols with Candida
      zeylanoides as a New Whole Cell Biocatalyst.
AB  - The increasing demand for biocatalysts in synthesizing enantiomerically pure
      chiral alcohols results from the outstanding characteristics of biocatalysts in
      reaction, economic, and ecological issues. Herein, fifteen yeast strains
      belonging to three food originated yeast species Candida zeylanoides, Pichia
      fermentans, and Saccharomyces uvarum were tested for their capability for
      asymmetric reduction of acetophenone to 1-phenylethanol as biocatalysts. Of these
      strains, C. zeylanoides P1 showed an effective asymmetric reduction ability.
      Under optimized conditions, substituted acetophenones were converted to
      corresponding optically active secondary alcohols in up to 99% enantiomeric
      excess and at high yields. The preparative scale asymmetric bioreduction of 4
      nitroacetophenone (1m) by C. zeylanoides P1 gave (S)-1-(4-nitrophenyl)ethanol
      (2m) with 89% yield and > 99% enantiomeric excess. Compound 2m has been obtained
      in an enantiomerically pure and inexpensive form. Additionally, these results
      indicate that C. zeylanoides P1 is a promising biocatalyst for the synthesis of
      chiral alcohols in industry.

PMID- 28746772
TI  - Enantioselective Tandem Cyclization of Alkyne-Tethered Indoles Using Cooperative
      Silver(I)/Chiral Phosphoric Acid Catalysis.
AB  - Reported is the enantioselective synthesis of tetracyclic indolines using
      silver(I)/chiral phosphoric acid catalysis. A variety of alkyne-tethered indoles
      are suitable for this process. Mechanistic studies suggest that the in situ
      generated silver(I) chiral phosphate activates both the alkyne and the indole
      nucleophile in the initial cyclization step through an intermolecular hydrogen
      bond and the phosphate anion promotes proton transfer. In addition, further
      modifications of the cyclization products enabled stereochemistry-function
      studies of a series of bioactive indolines.

PMID- 28746773
TI  - Overexpression of leucine-rich alpha2-glycoprotein-1 is a prognostic marker and
      enhances tumor migration in gastric cancer.
AB  - Gastric cancer is one of the most common malignant tumors. Although improvement
      in chemotherapy has been achieved, the clinical prognosis of advanced gastric
      cancer remains poor. Therefore, it is increasingly important to predict the
      prognosis and determine whether patients should or should not receive neoadjuvant
      or adjuvant chemotherapy. Leucine-rich alpha2-glycoprotein-1 (LRG1) is
      overexpressed during inflammation and is associated with various malignancies. In
      this study, we assessed LRG1 expression in cancer specimens and in the sera of
      patients with cancer to clarify the usefulness of LRG1 as a biomarker in gastric
      cancer. This study enrolled 239 (for immunohistochemical staining; IHC) and 184
      (for ELISA) patients with gastric cancer. Results of IHC showed that LRG1
      expression was significantly associated with histological type, lymphatic and
      venous invasion, tumor and node factors, and disease stage. Overall survival was
      significantly worse in the high LRG1 expression group than in the low LRG1 group
      (P = 0.0003). Cox multivariate analysis of overall survival revealed that LRG1
      expression was an independent prognostic factor (P = 0.0258). Serum LRG1 was
      significantly higher in gastric cancer patients than in healthy volunteers, and
      increased as the pathological stage progressed. Furthermore, a significant
      correlation was revealed between serum LRG1 level and LRG1 expression with IHC (P
      < 0.0001). Inhibition of LRG1 significantly decreased cell proliferation in vitro
      (migratory and invasive capacity of gastric cancer cells). These results suggest
      that LRG1 expression in tumors and serum may be a useful prognostic marker in
      gastric cancer patients.

PMID- 28746774
TI  - Knowledge, understanding and experiences of peritonitis amongst patients, and
      their families, undertaking peritoneal dialysis: A mixed methods study protocol.
AB  - AIM: This article is a report of a study protocol designed to examine patients'
      and families' knowledge and experiences of peritoneal dialysis-associated
      peritonitis. BACKGROUND: Peritonitis is a considerable problem for people using
      peritoneal dialysis, leading to antibiotics, hospitalization and decreased
      quality of life. For some patients, peritonitis requires changing renal
      replacement therapy and can be fatal. Peritonitis is distressing and some
      patients are unfamiliar with the signs and symptoms. Patients with better
      knowledge of peritonitis and adherence to peritoneal dialysis procedures have
      lower rates of peritonitis. Little is known about patients' and families'
      knowledge and experience of peritoneal dialysis-associated peritonitis in the
      United Kingdom. DESIGN: Ethical approval was gained in March 2017. To meet the
      study aim, a two-phase sequential explanatory mixed methods study is proposed.
      METHODS: Phase One: An author-developed questionnaire will be sent to patients
      using peritoneal dialysis at five sites in England and Wales. Patients will be
      asked to consider inviting a relative to participate. The questionnaire will
      assess peritonitis knowledge and experience. Data will be analysed statistically.
      Phase Two: Semi-structured interviews will be conducted with a purposive sample
      of Phase One participants (n = 30) to explore their experiences of peritonitis in
      further depth. The data will be analysed thematically using Wolcott's (1994)
      approach. DISCUSSION: Data from the two phases will be synthesized to identify
      patients' and families' peritonitis information needs, to ensure they are
      appropriately supported to prevent, monitor, identify and report peritonitis.

PMID- 28746775
TI  - Spatial connectivity in an adult-sedentary reef fish with extended pelagic larval
      phase.
AB  - Understanding the spatial scale of demographic connectivity in marine reef fishes
      dispersing pelagic larvae is a challenging task because of the technical
      difficulties associated with tagging and monitoring the movements of progeny at
      early life stages. Several studies highlighted a strong importance of local
      retention with levels of dispersal of ecological significance restricted to short
      distances. To date little information is available in species where pelagic
      dispersal lasts for long periods of time. In this work, population structure and
      connectivity were studied in the grey triggerfish, Balistes capriscus. Grey
      triggerfish larvae and juveniles remain associated with floating Sargassum sp.
      beds for an estimated period of 4-7 months before settling on benthic habitats
      where they remain sedentary as adults. Analysis of genetic variation among
      populations along the continental shelf of the northern Gulf of Mexico and U.S.
      east coast, encompassing over 3,100 km of coastline, revealed homogeneous allele
      frequencies and a weak isolation-by-distance pattern. Moment and maximum
      likelihood estimates of dispersal parameters both indicated occurrence of large
      neighbourhoods with estimates of the dispersal distribution parameter sigma of
      914 and 780 km, respectively. Simulated distributions of dispersal distances
      using several distribution functions all featured substantial fractions of long
      distance dispersal events with the 90% percentiles of travel distance prior to
      settlement averaging 1,809 km. These results suggest a high dependency of local
      recruitment on the output of nonlocal spawning stocks located hundreds of
      kilometres away and a reduced role of local retention in this species.

PMID- 28746776
TI  - External cervical resorption: a three-dimensional classification.
AB  - This article describes a novel three-dimensional classification for external
      cervical resorption (ECR). The European Society of Endodontology and American
      Association of Endodontists & American Academy of Oral & Maxillofacial Radiology
      position statements advise that Cone beam computed tomography should be
      considered for the assessment and/or management of root resorption if it appears
      to be clinically amenable to treatment following clinical and conventional
      radiographic examination. The new classification takes into account the ECR
      lesion height (1: at CEJ level or coronal to the bone crest (supracrestal), 2:
      extends into the coronal third of the root and apical to the bone crest
      (subcrestal), 3: extends into the mid-third of the root, 4: extends into the
      apical third of the root), circumferential spread (A: <=90 degrees  B: <=180
      degrees  C: <=270 degrees  D: >270 degrees ) and proximity to the root canal (d:
      lesion confined to dentine, p: probable pulpal involvement), thus classifying ECR
      in three dimensions. At present, there is no classification to accurately
      describe ECR. This novel and clinically relevant three-dimensional classification
      should allow effective and accurate communication of ECR lesions between
      colleagues. It will also allow the effect of the nature of ECR on the outcome of
      treatment to be assessed objectively.

PMID- 28746777
TI  - Functionality of intrinsic disorder in tumor necrosis factor-alpha and its
      receptors.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic inflammatory cytokine
      that exerts potent cytotoxic effects on solid tumor cells, while not affecting
      their normal counterparts. It is also known that TNF-alpha exerts many of its
      biological functions via interaction with specific receptors. To understand the
      potential roles of intrinsic disorder in the functioning of this important
      cytokine, we explored the peculiarities of intrinsic disorder distribution in
      human TNF-alpha and its homologs from various species, ranging from zebrafish to
      chimpanzee. We also studied the peculiarities of intrinsic disorder distribution
      in human TNF-alpha receptors, TNFR1 and TNFR2. Analysis revealed that cytoplasmic
      domains of TNF-alpha and its receptors are expected to be highly disordered.
      Furthermore, although the sequence identities of analyzed TNF-alpha homologs
      range from 99.57% (between human and chimpanzee proteins) to 22.33% (between frog
      and fish proteins), their intrinsic disorder profiles are characterized by a
      remarkable similarity. These observations indicate that the peculiarities of
      distribution of the intrinsic disorder propensity within the amino acid sequences
      are evolutionary conserved, and therefore could be of functional importance for
      this family of proteins. We also show that disordered and flexible regions of
      human TNF-alpha and its TNFR1 and TNFR2 receptors are crucial for some of their
      biological activities.

PMID- 28746778
TI  - Diagnostic application of BAP1 immunohistochemistry to differentiate pleural
      mesothelioma from metastatic pleural tumours.

PMID- 28746779
TI  - Hepatic farnesoid X receptor protein level and circulating fibroblast growth
      factor 19 concentration in children with NAFLD.
AB  - BACKGROUND & AIMS: Treatment with the farnesoid X receptor (FXR) agonist
      obeticholic acid is ineffective in some patients with non-alcoholic
      steatohepatitis (NASH) but the explanation is uncertain. We investigated hepatic
      FXR expression, and measurements of fibroblast growth factor 19 (FGF19) and bile
      acids (BAs) in children with NAFLD to investigate relationships with NASH.
      METHODS: 33 children with NAFLD who underwent diagnostic liver biopsy were
      studied. Hepatic FXR protein levels and circulating FGF19 concentrations were
      compared with those analysed in five control subjects with proven normal liver
      histology. NASH was defined by the Paediatric NAFLD Histological Score (PNHS).
      Binary logistic regression with adjustment for covariates and potential
      confounders was undertaken to test factors independently associated with: a) NASH
      and b) hepatic FXR protein levels. RESULTS: Mean +/- SD age was 13.7 +/- 1.9
      years. Nineteen patients had NASH (PNHS >= 85) and 14 did not have NASH (PNHS <
      85). Hepatic FXR level and plasma FGF19 concentration varied ~10-fold and 5-fold,
      respectively, between groups, and was highest in control subjects, intermediate
      in NAFLD without NASH, and lowest in NASH (between group differences P < .001 and
      P < .01 respectively). NASH was independently associated with both FXR protein
      levels (OR = 0.18, 95% CI 0.09, 0.38) and FGF19 concentration (OR = 0.55, 95% CI
      0.20, 0.89). CONCLUSIONS: FXR protein levels vary markedly between normal liver,
      NAFLD without NASH, and NASH. Low levels of FXR are independently associated with
      NASH.

PMID- 28746780
TI  - Kava-241 reduced periodontal destruction in a collagen antibody primed
      Porphyromonas gingivalis model of periodontitis.
AB  - AIM: The aim of this study was to evaluate the effect of Kava-241, an optimized
      Piper methysticum Kava compound, on periodontal destruction in a collagen
      antibody primed oral gavage model of periodontitis. METHODS: Experimental
      periodontitis was induced by oral gavage of Porphyromonas gingivalis (P.
      gingivalis) + type II collagen antibody (AB) in mice during 15 days. Mice were
      treated with Kava-241 concomitantly or prior to P. gingivalis gavage and compared
      to untreated mice. Comprehensive histomorphometric analyses were performed.
      RESULTS: Oral gavage with P. gingivalis induced mild epithelial down-growth and
      alveolar bone loss, while oral gavage with additional AB priming had greater
      tissular destruction in comparison with gavage alone (p < .05). Kava-241
      treatment significantly (p < .05) reduced epithelial down-growth (72%) and
      alveolar bone loss (36%) in P. gingivalis+AB group. This Kava-241 effect was
      associated to a reduction in inflammatory cell counts within soft tissues and an
      increase in fibroblasts (p < .05). CONCLUSION: Priming with type II collagen
      antibody with oral gavage is a fast and reproducible model of periodontal
      destruction adequate for the evaluation of novel therapeutics. The effect of Kava
      241 shows promise in the prevention and treatment of inflammation and alveolar
      bone loss associated with periodontitis. Further experiments are required to
      determine molecular pathways targeted by this therapeutic agent.

PMID- 28746781
TI  - Human herpesvirus-6 encephalitis following chemotherapy induction for acute
      myelogenous leukemia.
AB  - We report a case of human herpesvirus-6 (HHV-6) encephalitis in a neutropenic
      patient who had undergone chemotherapy induction for acute myelogenous leukemia
      while on broad-spectrum antimicrobial therapy. The patient displayed symptoms of
      confusion, amnesia, and lethargy. Diagnosis was made via polymerase chain
      reaction analysis of cerebrospinal fluid. Electroencephalogram and magnetic
      resonance imaging of the brain were unremarkable. Following diagnosis, the
      patient was successfully treated with ganciclovir. HHV-6 encephalitis should be
      considered in immunocompromised patients who become encephalopathic.

PMID- 28746782
TI  - Cytoplasmic rods and rings in mycophenolic acid treatment.

PMID- 28746783
TI  - CD73 expression identifies a subset of IgM+ antigen-experienced cells with memory
      attributes that is T cell and CD40 signalling dependent.
AB  - B-cell memory was long characterized as isotype-switched, somatically mutated and
      germinal centre (GC)-derived. However, it is now clear that the memory pool is a
      complex mixture that includes unswitched and unmutated cells. Further, expression
      of CD73, CD80 and CD273 has allowed the categorization of B-cell memory into
      multiple subsets, with combinatorial expression of the markers increasing with GC
      progression, isotype-switching and acquisition of somatic mutations. We have
      extended these findings to determine whether these markers can be used to
      identify IgM memory phenotypically as arising from T-dependent versus T
      independent responses. We report that CD73 expression identifies a subset of
      antigen-experienced IgM+ cells that share attributes of functional B-cell memory.
      This subset is reduced in the spleens of T-cell-deficient and CD40-deficient mice
      and in mixed marrow chimeras made with mutant and wild-type marrow, the
      proportion of CD73+ IgM memory is restored in the T-cell-deficient donor
      compartment but not in the CD40-deficient donor compartment, indicating that CD40
      ligation is involved in its generation. We also report that CD40 signalling
      supports optimal expression of CD73 on splenic T cells and age-associated B cells
      (ABCs), but not on other immune cells such as neutrophils, marginal zone B cells,
      peritoneal cavity B-1 B cells and regulatory T and B cells. Our data indicate
      that in addition to promoting GC-associated memory generation during B-cell
      differentiation, CD40-signalling can influence the composition of the unswitched
      memory B-cell pool. They also raise the possibility that a fraction of ABCs may
      represent T-cell-dependent IgM memory.

PMID- 28746784
TI  - Whole-genome sequencing approaches for conservation biology: Advantages,
      limitations and practical recommendations.
AB  - Whole-genome resequencing (WGR) is a powerful method for addressing fundamental
      evolutionary biology questions that have not been fully resolved using
      traditional methods. WGR includes four approaches: the sequencing of individuals
      to a high depth of coverage with either unresolved or resolved haplotypes, the
      sequencing of population genomes to a high depth by mixing equimolar amounts of
      unlabelled-individual DNA (Pool-seq) and the sequencing of multiple individuals
      from a population to a low depth (lcWGR). These techniques require the
      availability of a reference genome. This, along with the still high cost of
      shotgun sequencing and the large demand for computing resources and storage, has
      limited their implementation in nonmodel species with scarce genomic resources
      and in fields such as conservation biology. Our goal here is to describe the
      various WGR methods, their pros and cons and potential applications in
      conservation biology. WGR offers an unprecedented marker density and surveys a
      wide diversity of genetic variations not limited to single nucleotide
      polymorphisms (e.g., structural variants and mutations in regulatory elements),
      increasing their power for the detection of signatures of selection and local
      adaptation as well as for the identification of the genetic basis of phenotypic
      traits and diseases. Currently, though, no single WGR approach fulfils all
      requirements of conservation genetics, and each method has its own limitations
      and sources of potential bias. We discuss proposed ways to minimize such biases.
      We envision a not distant future where the analysis of whole genomes becomes a
      routine task in many nonmodel species and fields including conservation biology.

PMID- 28746785
TI  - Half the story: Thermal effects on within-host infectious disease progression in
      a warming climate.
AB  - Immune defense is temperature dependent in cold-blooded vertebrates (CBVs) and
      thus directly impacted by global warming. We examined whether immunity and within
      host infectious disease progression are altered in CBVs under realistic climate
      warming in a seasonal mid-latitude setting. Going further, we also examined how
      large thermal effects are in relation to the effects of other environmental
      variation in such a setting (critical to our ability to project infectious
      disease dynamics from thermal relationships alone). We employed the three-spined
      stickleback and three ecologically relevant parasite infections as a "wild"
      model. To generate a realistic climatic warming scenario we used naturalistic
      outdoors mesocosms with precise temperature control. We also conducted laboratory
      experiments to estimate thermal effects on immunity and within-host infectious
      disease progression under controlled conditions. As experimental readouts we
      measured disease progression for the parasites and expression in 14 immune
      associated genes (providing insight into immunophenotypic responses). Our
      mesocosm experiment demonstrated significant perturbation due to modest warming
      (+2 degrees C), altering the magnitude and phenology of disease. Our laboratory
      experiments demonstrated substantial thermal effects. Prevailing thermal effects
      were more important than lagged thermal effects and disease progression increased
      or decreased in severity with increasing temperature in an infection-specific
      way. Combining laboratory-determined thermal effects with our mesocosm data, we
      used inverse modeling to partition seasonal variation in Saprolegnia disease
      progression into a thermal effect and a latent immunocompetence effect (driven by
      nonthermal environmental variation and correlating with immune gene expression).
      The immunocompetence effect was large, accounting for at least as much variation
      in Saprolegnia disease as the thermal effect. This suggests that managers of CBV
      populations in variable environments may not be able to reliably project
      infectious disease risk from thermal data alone. Nevertheless, such projections
      would be improved by primarily considering prevailing thermal effects in the case
      of within-host disease and by incorporating validated measures of
      immunocompetence.

PMID- 28746786
TI  - Seed origin and warming constrain lodgepole pine recruitment, slowing the pace of
      population range shifts.
AB  - Understanding how climate warming will affect the demographic rates of different
      ecotypes is critical to predicting shifts in species distributions. Here, we
      present results from a common garden, climate change experiment in which we
      measured seedling recruitment of lodgepole pine, a widespread North American
      conifer that is also planted globally. Seeds from a low-elevation provenance had
      more than three-fold greater recruitment to their third year than seeds from a
      high-elevation provenance across sites within and above its native elevation
      range and across climate manipulations. Heating halved recruitment to the third
      year of both low- and high-elevation seed sources across the elevation gradient,
      while watering more than doubled recruitment, alleviating some of the negative
      effects of heating. Demographic models based on recruitment data from the climate
      manipulations and long-term observations of adult populations revealed that
      heating could effectively halt modeled upslope range expansion except when
      combined with watering. Simulating fire and rapid postfire forest recovery at
      lower elevations accelerated lodgepole pine expansion into the alpine, but did
      not alter final abundance rankings among climate scenarios. Regardless of climate
      scenario, greater recruitment of low-elevation seeds compensated for longer
      dispersal distances to treeline, assuming colonization was allowed to proceed
      over multiple centuries. Our results show that ecotypes from lower elevations
      within a species' range could enhance recruitment and facilitate upslope range
      shifts with climate change.

PMID- 28746787
TI  - Serum glypican 4 level in obese children and its relation to degree of obesity.
AB  - OBJECTIVE: Previous adult studies have demonstrated associations of serum
      glypican 4 (Gpc4) and obesity parameters and insulin sensitivity. However, an
      association of serum Gpc4 and glucose metabolism remains contradictory. Study of
      serum Gpc4 in obese children has not been conducted. We aimed to determine serum
      Gpc4 levels in obese children with various degrees of obesity. DESIGN, PATIENTS
      AND MEASUREMENTS: Up to 370 overweight and obese children, aged 6-18 years were
      enrolled in this cross-sectional study. Oral glucose tolerance test (OGTT) was
      performed with fasting serum Gpc4, lipid profiles, aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT) measured. Insulin sensitivity and beta
      cell function indices were calculated from plasma glucose and serum insulin
      levels derived from the OGTT. Bioelectrical impedance analysis was performed for
      body fat determination. Comparisons of serum Gpc4 levels among the groups of
      children with various degrees of obesity were performed. RESULTS: Serum Gpc4
      levels progressively increased in children with increasing body mass index
      standard deviation score (BMI SDS) tertiles [median (interquartile range, IQR):
      2.3 (1.8, 3.2), 2.6 (1.9, 3.4) and 3.2 (2.4, 3.8) MUg/L, P<.001]. There were no
      differences in serum Gpc4 levels among children in the different glucose
      metabolism categories. Log serum Gpc4 levels were positively correlated with SDSs
      of weight and BMI, cholesterol, AST and ALT. No associations of log serum Gpc4
      and insulin sensitivity and beta-cell function indices were demonstrated.
      CONCLUSIONS: Serum Gpc4 levels were increased with increasing degrees of obesity.
      There were no differences in serum Gpc4 levels among glucose metabolism
      categories.

PMID- 28746788
TI  - A randomized placebo-controlled trial of prophylactic dexamethasone for
      transcatheter arterial chemoembolization.
AB  - : This randomized, double-blind, placebo-controlled trial evaluated dexamethasone
      efficacy at preventing fever, anorexia, and nausea/vomiting, the most frequent
      adverse events of transcatheter arterial chemoembolization (TACE) in patients
      with hepatocellular carcinoma (HCC). Child-Pugh class A/B patients with HCC and
      no macrovascular invasion/extrahepatic metastases were randomly assigned to
      either a dexamethasone regimen (day 1, intravenous dexamethasone [20 mg] and
      granisetron [3 mg] before TACE; days 2 and 3, intravenous dexamethasone [8 mg])
      or a control regimen (day 1, intravenous placebo [saline] and granisetron [3 mg];
      days 2 and 3, intravenous placebo). The primary endpoint was complete response,
      defined as the absence of grade >=1 fever, anorexia, or nausea/vomiting according
      to the Common Terminology Criteria for Adverse Events (version 4.0) and no use of
      rescue therapy for 120 hours after TACE. A total of 120 patients between October
      2010 and June 2013 were randomly assigned to treatment groups. Overall the
      complete response rate was greater with the dexamethasone regimen than with the
      control regimen (47.5%, 95% confidence interval 34.3%-60.9%, versus 10.2%, 95%
      confidence interval 3.8%-20.8%; P < 0.001). Cumulative incidences of fever,
      anorexia, and nausea/vomiting were higher in the control regimen group compared
      with the dexamethasone group (P < 0.001, P < 0.001, and P = 0.095, respectively).
      The dexamethasone regimen was generally well tolerated by HCC patients including
      those with well-controlled diabetes mellitus and those with hepatitis B virus
      infection. CONCLUSION: The dexamethasone regimen was more effective than the
      control regimen at preventing TACE-induced fever, anorexia, and nausea/vomiting
      in patients with HCC. (Hepatology 2017).

PMID- 28746789
TI  - Cytogenetic clonal evolution in myelodysplastic syndromes is associated with
      inferior prognosis.
AB  - BACKGROUND: The karyotype of bone marrow cells at the time of diagnosis is a
      strong prognostic parameter for overall survival as well as acute myeloid
      leukemia (AML) progression in patients with myelodysplastic syndromes (MDS).
      However, to the authors' knowledge, few data exist regarding the prognostic
      impact of cytogenetic clonal evolution during the course of MDS. METHODS: The
      authors evaluated follow-up karyotype analyses in 549 patients from the
      Dusseldorf MDS Registry. RESULTS: Clonal evolution was detectable in 24% of the
      entire cohort and in 18% of 294 patients receiving best supportive care. The
      authors noted a clear adverse effect of clonal evolution on the risk of leukemic
      transformation (hazard ratio, 2.233; P = .036) and overall survival (hazard
      ratio, 3.677; P<.001). The authors also analyzed the prognostic influence of
      subclones detectable at the time of diagnosis. Again, such a finding was
      associated with a significantly shorter overall survival and a higher 5-year
      probability of acute myeloid leukemia progression (30% vs 22%). CONCLUSIONS: The
      results of the current study support the belief that follow-up karyotype analyses
      should be performed, especially in patients with lower-risk and intermediate-risk
      MDS, to identify those patients who are at higher risk of disease progression and
      therefore might benefit from earlier or more intensive treatment. Cancer
      2017;123:4608-4616. (c) 2017 American Cancer Society.

PMID- 28746790
TI  - Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin
      6/STAT3 signaling pathway.
AB  - : Long noncoding RNAs can serve as oncogenes or tumor suppressors in human
      cancer; however, their biological functions and underlying mechanism in
      hepatocarcinogenesis are largely unknown. Here, we report a novel tumor
      suppressor long noncoding RNA on chromosome 8p12 (termed TSLNC8) that is
      frequently deleted and down-regulated in hepatocellular carcinoma (HCC) tissues.
      The loss of TSLNC8 is highly associated with the malignant features of HCC and
      serves as a prognostic indicator for HCC patients. TSLNC8 significantly
      suppresses the proliferation and metastasis of HCC cells in vitro and in vivo.
      TSLNC8 exerts its tumor suppressive activity by competitively interacting with
      transketolase and signal transducer and activator of transcription 3 (STAT3) and
      modulating the STAT3-Tyr705 and STAT3-Ser727 phosphorylation levels and STAT3
      transcriptional activity, thus resulting in inactivation of the interleukin-6
      STAT3 signaling pathway in HCC cells. CONCLUSION: TSLNC8 is a promising
      prognostic predictor for patients with HCC, and the TSLNC8-transketolase-STAT3
      axis is a potential therapeutic target for HCC treatment. (Hepatology 2018;67:171
      187).

PMID- 28746791
TI  - Living donor follow-up: Unfunded mandates and the Hippocratic oath where perfect
      may be the enemy of good?

PMID- 28746792
TI  - Rate of warming affects temperature sensitivity of anaerobic peat decomposition
      and greenhouse gas production.
AB  - Temperature sensitivity of anaerobic carbon mineralization in wetlands remains
      poorly represented in most climate models and is especially unconstrained for
      warmer subtropical and tropical systems which account for a large proportion of
      global methane emissions. Several studies of experimental warming have documented
      thermal acclimation of soil respiration involving adjustments in microbial
      physiology or carbon use efficiency (CUE), with an initial decline in CUE with
      warming followed by a partial recovery in CUE at a later stage. The variable CUE
      implies that the rate of warming may impact microbial acclimation and the rate of
      carbon-dioxide (CO2 ) and methane (CH4 ) production. Here, we assessed the
      effects of warming rate on the decomposition of subtropical peats, by applying
      either a large single-step (10 degrees C within a day) or a slow ramping (0.1
      degrees C/day for 100 days) temperature increase. The extent of thermal
      acclimation was tested by monitoring CO2 and CH4 production, CUE, and microbial
      biomass. Total gaseous C loss, CUE, and MBC were greater in the slow (ramp)
      warming treatment. However, greater values of CH4 -C:CO2 -C ratios lead to a
      greater global warming potential in the fast (step) warming treatment. The effect
      of gradual warming on decomposition was more pronounced in recalcitrant and
      nutrient-limited soils. Stable carbon isotopes of CH4 and CO2 further indicated
      the possibility of different carbon processing pathways under the contrasting
      warming rates. Different responses in fast vs. slow warming treatment combined
      with different endpoints may indicate alternate pathways with long-term
      consequences. Incorporations of experimental results into organic matter
      decomposition models suggest that parameter uncertainties in CUE and CH4 -C:CO2 
      C ratios have a larger impact on long-term soil organic carbon and global warming
      potential than uncertainty in model structure, and shows that particular rates of
      warming are central to understand the response of wetland soils to global climate
      change.

PMID- 28746793
TI  - EASI-IMS an expedite and secure technique to screen for 25I-NBOH in blotter
      papers.
AB  - The increasing number of new psychoactive substances (NPS) and their quick
      worldwide spreading, often only slightly modified in the form of new derivatives
      and analogues, have brought the need for fast, wide-ranging, and unequivocal
      identification methods in clinical and forensic investigations. Because it
      usually provides secure results, gas chromatography coupled to mass spectrometry
      (GC-MS) has been routinely employed as the standard technique for the detection
      of NPS in blotter papers. For 25I-NBOH (N-(2-hydroxybenzyl)-2-(4-iodo-2,5
      dimethoxyphenyl)ethan-1-aminium), however, GC-MS analysis of an blotter paper
      extract leads to incorrect results. In this work, we investigated whether easy
      ambient sonic-spray mass spectrometry imaging (EASI-IMS), and ambient ionization
      MS method can be applied directly to the surface of the sample requiring
      therefore no extraction or sample preparations, would serve as an efficient,
      sensitive, and secure alternative for 25I-NBOH screening.

PMID- 28746794
TI  - Response to: shift in paradigm of clinical management of anastomotic leak.

PMID- 28746795
TI  - ICS 2017 Abstracts.

PMID- 28746796
TI  - Association between coffee consumption and all-sites cancer incidence and
      mortality.
AB  - The preventive effect of coffee on cancer at different sites has been reported,
      but the effect on all-sites cancer incidence has not been extensively
      investigated. We evaluated the association between frequency of coffee
      consumption and risk of all-sites cancer incidence and mortality among 39 685 men
      and 43 124 women (age 40-79 years, at baseline), in the Three-Prefecture Cohort
      Study. The association between frequency of coffee consumption and risk of all
      sites cancer incidence and mortality was assessed by a Cox proportional hazards
      regression model, adjusted for potential confounders. During 411 341 person-years
      among men and 472 433 person-years among women, a total of 4244 men and 2601
      women developed cancer at different sites and a total of 3021 men and 1635 women
      died of cancer at different sites. We showed an inverse association between
      frequency of coffee consumption and all-sites cancer incidence in both men and
      women. Comparing participants who consumed coffee with those who never drank
      coffee, the adjusted hazard ratios (95% confidential interval) for all-sites
      cancer incidence was 0.74 (0.62-0.88) for coffee consumption of >=5 cups/day in
      men (P for trend < 0.001) and 0.76 (0.58-1.02) in women (P for trend = 0.020).
      Coffee consumption frequency was inversely associated with mortality from all
      sites cancer. In this population, increasing coffee consumption resulted in a
      decreased risk of all-sites cancer incidence and mortality.

PMID- 28746797
TI  - A novel quantitative volumetric spreading index definition and assessment of
      astrocyte spreading in vitro.
AB  - A novel quantitative volumetric spreading index (VSI) is defined that depends on
      the total distance between object voxels and the contact surface plane in three
      dimensional (3D) space. The VSI, which ranges from 0 to 1, is rotationally
      invariant around the z-axis. VSI can be used to quantify the degree of individual
      cell spreading, which is important for analysis of cell interactions with their
      environment. The VSIs of astrocytes cultured on a nanofibrillar surface and three
      different comparative planar surfaces have been calculated from confocal laser
      scanning microscope z-series images, and the effects of both culture surface and
      immunoreactivity on the degree of cell spreading were investigated. VSI
      calculations indicated a statistical correlation between increased reactivity,
      based on immunolabeling for glial fibrillary acidic protein, and decreased cell
      spreading. Further results provided a quantitative measure for the increased
      spreading of quiescent-like and reactive-like astrocytes on planar substrates
      functionalized with poly-l-lysine. (c) 2017 International Society for Advancement
      of Cytometry.

PMID- 28746798
TI  - Thyroid disease symptoms during early pregnancy do not identify women with
      thyroid hypofunction that should be treated.
AB  - OBJECTIVE: To evaluate whether women during early pregnancy with "hypothyroidism"
      symptoms are at risk of biochemically defined hypothyroidism. The 2017 Guidelines
      of the American Thyroid Association (ATA) recommend case-finding on the basis of
      symptoms to identify these women during pregnancy, while evidence is lacking.
      DESIGN: Construct validation of a thyroid hypofunction symptom checklist during
      the first trimester of pregnancy comparing high scores with biochemically defined
      hypothyroidism. PATIENTS: A total of 2198 healthy pregnant women from an iodine
      sufficient area in 2013-2014. MEASUREMENTS: Completion of a draft questionnaire
      with "classical" symptoms of hypothyroidism at 12 weeks of gestation. The 2.5th
      and 97.5th percentiles of TSH and fT4 during pregnancy in TPO-Ab-negative (<35
      kU/L) women were used to define euthyroid women and those with overt (clinical)
      and subclinical hypothyroidism. The prevalence of overt (subclinical)
      hypothyroidism was compared between women with high symptom scores and those with
      low symptom scores. RESULTS: According to fT4 and TSH cut-offs (0.23-4.0 mIU/L
      and 11.5-18.0 pmol/L, respectively), there were 15 women with "to treat
      hypofunction" (overt hypothyroidism or TSH >10 mIU/L) and 68 women with
      subclinical hypothyroidism. Questionnaire construct validation revealed a 12-item
      hypothyroid checklist with normally distributed scores. The cut-off indicating
      high scores of OH was set at 1 SD > mean. Women with high symptom scores did not
      present more often with biochemically defined thyroid hypofunction. CONCLUSION:
      This study does not support the ATA recommendation that pregnant women who
      require levothyroxine therapy can be identified by case-based screening of women
      with symptoms of thyroid disease.

PMID- 28746799
TI  - Lack of interleukin-6 in the tumor microenvironment augments type-1 immunity and
      increases the efficacy of cancer immunotherapy.
AB  - Conquering immunosuppression in tumor microenvironments is crucial for effective
      cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic
      cytokine, is produced in the tumor-bearing state. In the present study, we
      investigated the precise effects of IL-6 on antitumor immunity and the subsequent
      tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell
      line, were intradermally injected into wild-type and IL-6-deficient mice. As a
      result, we found that tumor growth was decreased significantly in IL-6-deficient
      mice compared with wild-type mice and the reduction was abrogated by depletion of
      CD8+ T cells. We further evaluated the immune status of tumor microenvironments
      and confirmed that mature dendritic cells, helper T cells and cytotoxic T cells
      were highly accumulated in tumor sites under the IL-6-deficient condition. In
      addition, higher numbers of interferon (IFN)-gamma-producing T cells were present
      in the tumor tissues of IL-6-deficient mice compared with wild-type mice. Surface
      expression levels of programmed death-ligand 1 (PD-L1) and MHC class I on CT26
      cells were enhanced under the IL-6-deficient condition in vivo and by IFN-gamma
      stimulation in vitro. Finally, we confirmed that in vivo injection of an anti-PD
      L1 antibody or a Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid,
      effectively inhibited tumorigenesis under the IL-6-deficient condition. Based on
      these findings, we speculate that a lack of IL-6 produced in tumor-bearing host
      augments induction of antitumor effector T cells and inhibits tumorigenesis in
      vivo, suggesting that IL-6 signaling may be a promising target for the
      development of effective cancer immunotherapies.

PMID- 28746800
TI  - The changing nature of relationships between parents and healthcare providers
      when a child dies in the paediatric intensive care unit.
AB  - AIM: To explore bereaved parents' interactions with healthcare providers when a
      child dies in a paediatric intensive care unit. BACKGROUND: Although most
      children admitted to a paediatric intensive care unit will survive, 2-5% will die
      during their stay. The parents of these children interact and form relationships
      with numerous healthcare staff during their child's illness and death. Although
      previous studies have explored the parental experience of child death in
      intensive care generally, the nature of their relationships with healthcare
      providers during this time remains unknown. DESIGN: This study used a
      constructivist grounded theory approach. METHODS: Data were collected via semi
      structured, audio-recorded interviews with 26 bereaved parents from four
      paediatric intensive care units over 18 months in 2015-2016. Constant comparative
      analysis and theoretical memos were used to analyse the data. FINDINGS: The
      theory "Transitional togetherness" demonstrates the changing nature of the parent
      healthcare provider relationship across three key phases of the parents' journey.
      Phase one, "Welcoming expertise," focuses on the child's medical needs, with the
      healthcare provider dominant in the relationship. Phase two, "Becoming a team,"
      centres around the parents' need to recreate a parental role and work
      collaboratively with healthcare providers. Finally, "Gradually disengaging"
      describes the parents' desire for the relationship to continue after the child's
      death as a source of support until no longer needed. CONCLUSIONS: Findings from
      this study offer valuable insights into the changing nature of the parent
      healthcare provider relationship and highlight the key foci of the relationship
      at each stage of the parental journey.

PMID- 28746801
TI  - An automated quantitative image analysis tool for the identification of
      microtubule patterns in plants.
AB  - High throughput confocal imaging poses challenges in the computational image
      analysis of complex subcellular structures such as the microtubule cytoskeleton.
      Here, we developed CellArchitect, an automated image analysis tool that
      quantifies changes to subcellular patterns illustrated by microtubule markers in
      plants. We screened microtubule-targeted herbicides and demonstrate that high
      throughput confocal imaging with integrated image analysis by CellArchitect can
      distinguish effects induced by the known herbicides indaziflam and trifluralin.
      The same platform was used to examine 6 other compounds with herbicidal activity,
      and at least 3 different effects induced by these compounds were profiled. We
      further show that CellArchitect can detect subcellular patterns tagged by actin
      and endoplasmic reticulum markers. Thus, the platform developed here can be used
      to automate image analysis of complex subcellular patterns for purposes such as
      herbicide discovery and mode of action characterisation. The capacity to use this
      tool to quantitatively characterize cellular responses lends itself to
      application across many areas of biology.

PMID- 28746802
TI  - Leading by gaslight? Nursing's academic leadership struggles.

PMID- 28746803
TI  - Topical tocopherol for the treatment of reticular oral lichen planus: Randomized,
      double-blind crossover study - A query.

PMID- 28746804
TI  - A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of
      HDAC6 Inhibitors.
AB  - We herein present broadly useful, readily available and nonintegral hydroxylamine
      linkers for the routine solid-phase synthesis of hydroxamic acids. The developed
      protocols enable the efficient synthesis and release of a wide range of
      hydroxamic acids from various resins, relying on high control and flexibility
      with respect to reagents and synthetic processes. A trityl-based hydroxylamine
      linker was used to synthesize a library of peptide hydroxamic acids. The
      inhibitory effects of the compounds were examined for seven HDAC enzyme subtypes
      using a chemiluminescence-based assay.

PMID- 28746805
TI  - All-Atom MD Simulation of DNA Condensation Using Ab Initio Derived Force Field
      Parameters of Cobalt(III)-Hexammine.
AB  - It is well established that the presence of the trivalent cobalt(III)-hexammine
      cation (CoHex3+) at submillimolar concentrations leads to bundling (condensation)
      of double-stranded DNA molecules, which is caused by DNA-DNA attraction induced
      by the multivalent counterions. However, the detailed mechanism of this process
      is still not fully understood. Furthermore, in all-atom molecular dynamics (MD)
      simulations, spontaneous aggregation of several DNA oligonucleotides in the
      presence of CoHex3+ has previously not been demonstrated. In order to obtain a
      rigorous description of CoHex3+-nucleic acid interactions and CoHex3+-induced DNA
      condensation to be used in MD simulations, we have derived optimized force field
      parameters of the CoHex3+ ion. They were obtained from Car-Parrinello molecular
      dynamics simulation of a single CoHex3+ ion in the presence of 125 water
      molecules. The new set of force field parameters reproduces the experimentally
      known transition of DNA from B- to A-form, and qualitatively describes changes of
      DNA and RNA persistence lengths. We then carried out a 2 MUs long atomistic
      simulation of four DNA oligomers each consisting of 36 base pairs in the presence
      of CoHex3+. We demonstrate that, in this system, DNA molecules display attractive
      interactions and aggregate into bundle-like structures. This behavior depends
      critically on the details of the CoHex3+ interaction with DNA. A control
      simulation with a similar setup but in the presence of Mg2+ does not induce DNA
      DNA attraction, which is also in agreement with experiment.

PMID- 28746806
TI  - Disposable Amperometric Polymerase Chain Reaction-Free Biosensor for Direct
      Detection of Adulteration with Horsemeat in Raw Lysates Targeting Mitochondrial
      DNA.
AB  - A novel electrochemical disposable nucleic acid biosensor for simple, rapid, and
      specific detection of adulterations with horsemeat is reported in this work. The
      biosensing platform involves immobilization of a 40-mer RNA probe specific for a
      characteristic fragment of the mitochondrial DNA D-loop region of horse onto the
      surface of magnetic microcarriers. In addition, signal amplification was
      accomplished by using a commercial antibody specific to RNA/DNA duplexes and a
      bacterial protein conjugated with a horseradish peroxidase homopolymer (ProtA
      HRP40). Amperometric detection at -0.20 V vs Ag pseudoreference electrode was
      carried out at disposable screen-printed carbon electrodes. The methodology
      achieved a limit of detection (LOD) of 0.12 pM (3.0 attomoles) for the synthetic
      target and showed ability to discriminate between raw beef and horsemeat using
      just 50 ng of total extracted mitochondrial DNA (~16 660 bp in length) without
      previous fragmentation. The biosensor also allowed discrimination between 100%
      raw beef and beef meat samples spiked with only 0.5% (w/w) horse meat (levels
      established by the European Commission) using raw mitochondrial lysates without
      DNA extraction or polymerase chain reaction (PCR) amplification in just 75 min.
      These interesting features made the developed methodology an extremely
      interesting tool for beef meat screening, and it can be easily adapted to the
      determination of other meat adulterations by selection of the appropriate
      specific fragments of the mitochondrial DNA region and capture probes.

PMID- 28746807
TI  - Sharpened VO2 Phase Transition via Controlled Release of Epitaxial Strain.
AB  - Phase transitions in correlated materials can be manipulated at the nanoscale to
      yield emergent functional properties, promising new paradigms for nanoelectronics
      and nanophotonics. Vanadium dioxide (VO2), an archetypal correlated material,
      exhibits a metal-insulator transition (MIT) above room temperature. At the
      thicknesses required for heterostructure applications, such as an optical
      modulator discussed here, the strain state of VO2 largely determines the MIT
      dynamics critical to the device performance. We develop an approach to control
      the MIT dynamics in epitaxial VO2 films by employing an intermediate template
      layer with large lattice mismatch to relieve the interfacial lattice constraints,
      contrary to conventional thin film epitaxy that favors lattice match between the
      substrate and the growing film. A combination of phase-field simulation, in situ
      real-time nanoscale imaging, and electrical measurements reveals robust
      undisturbed MIT dynamics even at preexisting structural domain boundaries and
      significantly sharpened MIT in the templated VO2 films. Utilizing the sharp MIT,
      we demonstrate a fast, electrically switchable optical waveguide. This study
      offers unconventional design principles for heteroepitaxial correlated materials,
      as well as novel insight into their nanoscale phase transitions.

PMID- 28746808
TI  - Effects of kisspeptin on diabetic rat platelets.
AB  - Hyperglycemia, hyperlipidemia, and free radicals result in platelet activation
      and atherogenesis. Kisspeptin (KP) is able to regulate metabolism, hemostasis,
      and the development of atherosclerosis. We examined whether platelet aggregation
      of streptozotocin-induced diabetic rats depends on the inducer type and if KP-13
      and RF-9 (a kisspeptin receptor modifier) can influence platelet function. We
      measured the speed and the maximum of aggregation, along with the area under the
      curve. Serum glucose and calcium levels and urine formation of diabetic animals
      increased, while the body mass and platelet count decreased. Collagen was the
      most effective inducer of platelet aggregation. The aggregability of nondiabetic
      platelets was elevated in the presence of 5 * 10-8 mol/L KP-13. This effect was
      less expressed in diabetic animals. The effectivity of RF-9 was stronger than
      that of KP-13 in nondiabetic platelets, however it was ineffective in diabetic
      animals. RF-9 pre-treatment did not change the effects of 5 * 10-8 mol/L KP-13 in
      either animal group. The in vivo activation of diabetic platelets, which may be
      due to elevated serum calcium, induces thrombocytopenia and may lead to reduced
      in vitro aggregability. We could not demonstrate the antagonistic effect of RF-9
      against KP-13 in isolated platelets.

PMID- 28746809
TI  - Diagnosis of fetal alcohol spectrum disorder: current practices and future
      considerations.
AB  - This paper discusses the current state of knowledge and practice for diagnosing
      fetal alcohol spectrum disorder (FASD). The strengths and challenges of different
      models of diagnosis are compared. Some models require a team approach for
      evaluation, while other approaches assume that a clinician in his or her office
      provides a diagnosis based on a review of the patient's medical and social
      history, behaviour, and physical examination. The author reviews the emergence of
      new information from recent advances in genetics, imaging, and electrophysiology
      that has the potential to lead to changes in practice and improved reliability of
      an FASD diagnosis.

PMID- 28746810
TI  - Beat-to-beat variability of cardiac action potential duration: underlying
      mechanism and clinical implications.
AB  - Beat-to-beat variability of cardiac action potential duration (short-term
      variability, SV) is a common feature of various cardiac preparations, including
      the human heart. Although it is believed to be one of the best arrhythmia
      predictors, the underlying mechanisms are not fully understood at present. The
      magnitude of SV is basically determined by the intensity of cell-to-cell coupling
      in multicellular preparations and by the duration of the action potential (APD).
      To compensate for the APD-dependent nature of SV, the concept of relative SV
      (RSV) has been introduced by normalizing the changes of SV to the concomitant
      changes in APD. RSV is reduced by ICa, IKr, and IKs while increased by INa,
      suggesting that ion currents involved in the negative feedback regulation of APD
      tend to keep RSV at a low level. RSV is also influenced by intracellular calcium
      concentration and tissue redox potential. The clinical implications of APD
      variability is discussed in detail.

PMID- 28746811
TI  - The acute effects of different spironolactone doses on cardiac function in
      streptozotocin-induced diabetic rats.
AB  - Currently, cardiovascular diseases are the leading cause of global mortality,
      while diabetes mellitus remains an important cause of cardiovascular morbidity. A
      recent study showed that patients with diabetes mellitus treated with
      mineralocorticoid receptor antagonists have improved coronary microvascular
      function, leading to improved diastolic dysfunction. In this study, we evaluated
      the influence of acute administration of spironolactone on myocardial function in
      rats with streptozotocin-induced diabetes mellitus, with special emphasis on
      cardiodynamic parameters in diabetic rat hearts. The present study was carried
      out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided
      into 4 groups (10 animals per group): healthy rats treated with 0.1 MUmol/L of
      spironolactone, diabetic rats treated with 0.1 MUmol/L of spironolactone, healthy
      rats treated with 3 MUmol/L of spironolactone, and diabetic rats treated with 3
      MUmol/L of spironolactone. Different, dose-dependent, acute responses of
      spironolactone treatment on isolated, working diabetic and healthy rat heart were
      observed in our study. In healthy rats, better systolic function was achieved
      with higher spironolactone dose, while in diabetic rats, similar effects of low
      and high spironolactone dose were observed.

PMID- 28746812
TI  - Intra-articular Injection of Mesenchymal Stem Cells for the Treatment of
      Osteoarthritis of the Knee: A 2-Year Follow-up Study.
AB  - BACKGROUND: The intra-articular injection of mesenchymal stem cells (MSCs) into
      the knee has shown a potential for the treatment of generalized cartilage loss in
      osteoarthritis (OA). However, there have been few midterm reports with clinical
      and structural outcomes. PURPOSE: To assess the midterm safety and efficacy of an
      intra-articular injection of autologous adipose tissue-derived (AD) MSCs for knee
      OA at 2-year follow-up. STUDY DESIGN: Cohort study; Level of evidence, 3.
      METHODS: Eighteen patients with OA of the knee were enrolled (3 male, 15 female;
      mean age, 61.8 +/- 6.6 years [range, 52-72 years]). Patients in the low-, medium
      , and high-dose groups received an intra-articular injection of 1.0 * 107, 5.0 *
      107, and 1.0 * 108 AD MSCs into the knee, respectively. Clinical and structural
      evaluations were performed with widely used methodologies including the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and measurements
      of the size and depth of the cartilage defect, signal intensity of regenerated
      cartilage, and cartilage volume using magnetic resonance imaging (MRI). RESULTS:
      There were no treatment-related adverse events during the 2-year period. An intra
      articular injection of autologous AD MSCs improved knee function, as measured
      with the WOMAC, Knee Society clinical rating system (KSS), and Knee injury and
      Osteoarthritis Outcome Score (KOOS), and reduced knee pain, as measured with the
      visual analog scale (VAS), for up to 2 years regardless of the cell dosage.
      However, statistical significance was found mainly in the high-dose group.
      Clinical outcomes tended to deteriorate after 1 year in the low- and medium-dose
      groups, whereas those in the high-dose group plateaued until 2 years. The
      structural outcomes evaluated with MRI also showed similar trends. CONCLUSION:
      This study identified the safety and efficacy of an intra-articular injection of
      AD MSCs into the OA knee over 2 years, encouraging a larger randomized clinical
      trial. However, this study also showed potential concerns about the durability of
      clinical and structural outcomes, suggesting the need for further studies.
      CLINICAL TRIAL REGISTRATION: NCT01300598.

PMID- 28746814
TI  - Probabilistic Computations for Attention, Eye Movements, and Search.
AB  - The term visual attention immediately evokes the idea of limited resources,
      serial processing, or a zoom metaphor. But evidence has slowly accumulated that
      computations that take into account probabilistic relationships among visual
      forms and the target contribute to optimizing decisions in biological and
      artificial organisms, even without considering these limited-capacity processes
      in covert attention or even foveation. The benefits from such computations can be
      formalized within the framework of an ideal Bayesian observer and can be related
      to the classic theory of sensory cue combination in vision science and context
      driven approaches to object detection in computer vision. The framework can
      account for a large range of behavioral findings across distinct experimental
      paradigms, including visual search, cueing, and scene context. I argue that these
      forms of probabilistic computations might be fundamental to optimizing decisions
      in many species and review human experiments trying to identify scene properties
      that serve as cues to guide eye movements and facilitate search. I conclude by
      discussing contributions of attention beyond probabilistic computations but argue
      that the framework's merit is to unify many basic paradigms to study attention
      under a single theory.

PMID- 28746813
TI  - Binocular Mechanisms of 3D Motion Processing.
AB  - The visual system must recover important properties of the external environment
      if its host is to survive. Because the retinae are effectively two-dimensional
      but the world is three-dimensional (3D), the patterns of stimulation both within
      and across the eyes must be used to infer the distal stimulus-the environment-in
      all three dimensions. Moreover, animals and elements in the environment move,
      which means the input contains rich temporal information. Here, in addition to
      reviewing the literature, we discuss how and why prior work has focused on
      purported isolated systems (e.g., stereopsis) or cues (e.g., horizontal
      disparity) that do not necessarily map elegantly on to the computations and
      complex patterns of stimulation that arise when visual systems operate within the
      real world. We thus also introduce the binoptic flow field (BFF) as a description
      of the 3D motion information available in realistic environments, which can
      foster the use of ecologically valid yet well-controlled stimuli. Further, it can
      help clarify how future studies can more directly focus on the computations and
      stimulus properties the visual system might use to support perception and
      behavior in a dynamic 3D world.

PMID- 28746815
TI  - Higher-Order Areas of the Mouse Visual Cortex.
AB  - The brain has evolved to transform sensory information in the environment into
      neural representations that can be used for perception and action. Higher-order
      sensory cortical areas, with their increasingly complex receptive fields and
      integrative properties, are thought to be critical nodes for this function. This
      is especially true in the primate visual cortex, in which functionally
      specialized areas are engaged in parallel streams to support diverse
      computations. Recent anatomical and physiological studies of the mouse visual
      cortex have revealed a similarly complex network of specialized higher-order
      areas. This structure provides a useful model for determining the synaptic and
      circuit mechanisms through which information is transformed across distinct
      processing stages. In this review, we summarize the current knowledge on the
      layout, connectivity, and functional properties of the higher visual areas in the
      mouse. In addition, we speculate on the contribution of these areas to perception
      and action, and how knowledge of the mouse visual system can inform us about the
      principles that govern information processing in integrated networks.

PMID- 28746816
TI  - Expression of classical mediators in hearts of rats with hepatic dysfunction.
AB  - Liver cirrhosis is associated with impairment of cardiovascular function
      including alterations of the heart innervation, humoral and nervous
      dysregulation, changes in systemic circulation and electrophysiological
      abnormalities. Choline acetyltransferase (ChAT), enzyme forming acetylcholine,
      tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH), enzymes
      participating in noradrenaline synthesis, are responsible for the production of
      classical neurotransmitters, and atrial natriuretic peptide (ANP) is produced by
      cardiomyocytes. The aim of this study was to evaluate the influence of
      experimentally induced hepatic dysfunction on the expression of proANP, ChAT, TH,
      and DBH in the heart. Hepatic dysfunction was induced by application of
      thioacetamide (TAA) or by ligation of bile duct. Biochemical parameters of
      hepatic injury and levels of peroxidation in the liver and heart were measured.
      Liver enzymes measured in the plasma were significantly elevated. Cardiac level
      of peroxidation was increased in operated but not TAA group animals. In the left
      atrium of operated rats, the expression of TH and DBH was lower, while expression
      of ChAT remained unchanged. In TAA group, no significant differences in the
      expression of the genes compared to controls were observed. Liver injury induced
      by ligation leads to an imbalance in the intracardiac innervation, which might
      impair nervous control of the heart.

PMID- 28746817
TI  - Human bone marrow mesenchymal stem cells suppress the proliferation of hepatic
      stellate cells by inhibiting the ubiquitination of p27.
AB  - Bone marrow mesenchymal stem cells (BMSCs) have considerable therapeutic
      potential for the treatment of end-stage liver disease. Previous studies have
      demonstrated that BMSCs secrete growth factors and cytokines that inactivate
      hepatic stellate cells (HSCs), which inhibited the progression of hepatic
      fibrosis. The aim of this study was to determine the mechanism by which BMSCs
      suppress the function of HSCs in fibrosis. Our results showed that co-culture of
      BMSCs and HSCs induced cell cycle arrest at the G10/G1 phase and cell apoptosis
      of HSCs, which finally inhibited the cell proliferation of HSCs. Consistent with
      the cell cycle arrest, co-culture of BMSCs and HSCs increased the abundance of
      the cell cycle protein p27. Mechanistically, we further uncovered that following
      the co-culture with BMSCs, the expression level of the E3 ligase S-phase kinase
      associated protein 2 (SKP2) that is responsible for the ubiquitination of p27 was
      decreased, which attenuated the ubiquitination of p27 and increased the stability
      of p27 in HSCs. Collectively, our results indicated the potential involvement of
      the SKP2-p27 axis for the inhibitory effect of BSMCs on the cell proliferation of
      HSCs.

PMID- 28746818
TI  - The role of paraoxonase 1 in regulating high-density lipoprotein functionality
      during aging.
AB  - Pharmacological interventions to increase the concentration of high-density
      lipoprotein (HDL) have led to disappointing results and have contributed to the
      emergence of the concept of HDL functionality. The anti-atherogenic activity of
      HDLs can be explained by their functionality or quality. The capacity of HDLs to
      maintain cellular cholesterol homeostasis and to transport cholesterol from
      peripheral cells to the liver for elimination is one of their principal anti
      atherogenic activities. However, HDLs possess several other attributes that
      contribute to their protective effect against cardiovascular diseases. HDL
      functionality is regulated by various proteins and lipids making up HDL
      particles. However, several studies investigated the role of paraoxonase 1 (PON1)
      and suggest a significant role of this protein in the regulation of the
      functionality of HDLs. Moreover, research on PON1 attracted much interest
      following several studies indicating that it is involved in cardiovascular
      protection. However, the mechanisms by which PON1 exerts these effects remain to
      be elucidated.

PMID- 28746819
TI  - Humanized Mouse Models for Human Immunodeficiency Virus Infection.
AB  - Human immunodeficiency virus (HIV) remains a significant source of morbidity and
      mortality worldwide. No effective vaccine is available to prevent HIV
      transmission, and although antiretroviral therapy can prevent disease
      progression, it does not cure HIV infection. Substantial effort is therefore
      currently directed toward basic research on HIV pathogenesis and persistence and
      developing methods to stop the spread of the HIV epidemic and cure those
      individuals already infected with HIV. Humanized mice are versatile tools for the
      study of HIV and its interaction with the human immune system. These models
      generally consist of immunodeficient mice transplanted with human cells or
      reconstituted with a near-complete human immune system. Here, we describe the
      major humanized mouse models currently in use, and some recent advances that have
      been made in HIV research/therapeutics using these models.

PMID- 28746820
TI  - The role of damage- and pathogen-associated molecular patterns in inflammation
      mediated vulnerability of atherosclerotic plaques.
AB  - Atherosclerosis is a chronic inflammatory disease resulting in the formation of
      the atherosclerotic plaque. Plaque formation starts with the inflammation in
      fatty streaks and progresses through atheroma, atheromatous plaque, and
      fibroatheroma leading to development of stable plaque. Hypercholesterolemia,
      dyslipidemia, and hyperglycemia are the risk factors for atherosclerosis.
      Inflammation, infection with viruses and bacteria, and dysregulation in the
      endothelial and vascular smooth muscle cells leads to advanced plaque formation.
      Death of the cells in the intima due to inflammation results in secretion of
      damage-associated molecular patterns (DAMPs) such as high mobility group box 1
      (HMGB1), receptor for advanced glycation end products (RAGE), alarmins (S100A8,
      S100A9, S100A12, and oxidized low-density lipoproteins), and infection with
      pathogens leads to secretion of pathogen-associated molecular patterns (PAMPs)
      such as lipopolysaccharides, lipoteichoic acids, and peptidoglycans. DAMPs and
      PAMPs further activate the inflammatory surface receptors such as TREM-1 and toll
      like receptors and downstream signaling kinases and transcription factors leading
      to increased secretion of pro-inflammatory cytokines such as tumor necrosis
      factor alpha, interleukin (IL)-1beta, IL-6, and interferon-gamma and matrix
      metalloproteinases (MMPs). These mediators and cytokines along with MMPs render
      the plaque vulnerable for rupture leading to ischemic events. In this review, we
      have discussed the role of DAMPs and PAMPs in association with inflammation
      mediated plaque vulnerability.

PMID- 28746821
TI  - Cardiopulmonary Exercise Testing.

PMID- 28746822
TI  - Astrocyte-enriched feeder layers from cryopreserved cells support differentiation
      of spontaneously active networks of human iPSC-derived neurons.
AB  - BACKGROUND: Human induced pluripotent stem cell (hiPSC)-derived neuronal cultures
      are a useful tool for studying the mechanisms of neurological disorders and
      developing novel therapeutics. While plating hiPSC-derived neuronal progenitors
      onto glial feeder layers prepared from rodent cortex has been reported to promote
      functional differentiation of neuronal networks, this has not been examined in
      detail. NEW METHOD: Here we describe a method of using cryopreserved cells from
      primary cultures for generation of mouse astrocyte-enriched, neuron-free feeder
      layers that grow from 10% to 100% confluence in 1 week. RESULTS:
      Electrophysiological analysis demonstrated that compared to biochemical
      substrates alone, astrocyte-enriched feeder layers support more rapid
      differentiation of hiPSC-derived progenitors into excitable neurons that form
      spontaneously active networks in culture. There was a positive correlation
      between the degree of astroglial confluence at the time of progenitor plating and
      the average frequency of postsynaptic currents 3 weeks after plating. One
      disadvantage to plating on 100% confluent feeder layers was a high incidence of
      the astroglial layer with the overlying neurons detaching from the coverslips
      during transfer to the recording chamber. COMPARISON WITH EXISTING METHOD(S):
      Prevailing methods using primary glial feeder layers can result in possible
      contamination with rodent neurons and an unpredictable rate of growth. We provide
      a reliable method of generating mouse astroglial feeder layers from cryopreserved
      primary cultures to support differentiation of hiPSC-derived neurons.
      CONCLUSIONS: The ability to make astrocyte-enriched feeder layers of defined
      confluence from cryopreserved primary cultures will facilitate the use of human
      stem cell derived neuronal cultures for disease modeling.

PMID- 28746823
TI  - Irx1 regulates dental outer enamel epithelial and lung alveolar type II
      epithelial differentiation.
AB  - The Iroquois genes (Irx) appear to regulate fundamental processes that lead to
      cell proliferation, differentiation, and maturation during development. In this
      report, the Iroquois homeobox 1 (Irx1) transcription factor was functionally
      disrupted using a LacZ insert and LacZ expression demonstrated stage-specific
      expression during embryogenesis. Irx1 is highly expressed in the brain, lung,
      digits, kidney, testis and developing teeth. Irx1 null mice are neonatal lethal
      and this lethality it due to pulmonary immaturity. Irx1-/- mice show delayed lung
      maturation characterized by defective surfactant protein secretion and Irx1 marks
      a population of SP-C expressing alveolar type II cells. Irx1 is specifically
      expressed in the outer enamel epithelium (OEE), stellate reticulum (SR) and
      stratum intermedium (SI) layers of the developing tooth. Irx1 mediates dental
      epithelial cell differentiation in the lower incisors resulting in delayed growth
      of the lower incisors. Irx1 is specifically and temporally expressed during
      developmental stages and we have focused on lung and dental development in this
      report. Irx1+ cells are unique to the development of the incisor outer enamel
      epithelium, patterning of Lef-1+ and Sox2+ cells as well as a new marker for lung
      alveolar type II cells. Mechanistically, Irx1 regulates Foxj1 and Sox9 to control
      cell differentiation during development.

PMID- 28746824
TI  - Two new species of Simulium (Gomphostilbia) (Diptera: Simuliidae) from Myanmar,
      and their phylogenetic relationships with related species in the S. asakoae
      species-group.
AB  - Two new species of Simulium (Gomphostilbia), S. (G.) myanmarense and S. (G.)
      monglaense, are described from females, males, pupae and larvae from Myanmar. The
      two new species are placed in the S. asakoae species-group, and are similar to
      each other in the female and male but distinguished in the pupa by the presence
      or absence of an anterodorsal projection of the cocoon, and in the larva by a
      unique pattern of colored markings on the abdomen. Taxonomic notes are given to
      separate these species from related species. The COI gene sequences of both
      species are compared with those of eight species of the S. asakoae species-group
      and three species of the S. ceylonicum species-group. Both new species are most
      closely related to each other, further supporting their morphological
      classification in the S. asakoae species-group.

PMID- 28746825
TI  - Differential expression of glucagon-like peptide-2 (GLP-2) is involved in
      pancreatic islet cell adaptations to stress and beta-cell survival.
AB  - Recent studies have confirmed that locally released proglucagon derived gene
      products, other than glucagon, have a major influence on pancreatic endocrine
      function. We assessed the impact of glucagon-like peptide-2 (GLP-2) on beta-cell
      secretory function, proliferation and apoptosis, as well as glucose tolerance,
      feeding behaviour and islet adaptions to chemically-induced insulin deficiency
      and resistance. The GLP-2 receptor was evidenced on cultured rodent and human
      beta-cells, rodent alpha-cells and isolated mouse islets. GLP-2 had no effect on
      insulin secretion from beta-cells, or isolated mouse islets. In vivo, GLP-2
      administration significantly (P<0.05 to P<0.01) decreased food intake in mice.
      Conversely, GLP-2 had no discernible effects on glucose disposal or insulin
      secretion. As expected, streptozotocin treatment decreased and hydrocortisone
      increased beta-cell mass in mice. GLP-2 was visualised in mouse islets and
      intestinal L-cells. Islet GLP-2 co-localisation with glucagon was significantly
      decreased (P<0.01) by both streptozotocin and hydrocortisone. In contrast, both
      interventions increased (P<0.05) co-localisation of GLP-2 with somatostatin.
      Interestingly, GLP-2 positive cells were reduced (P<0.05) in the intestines of
      streptozotocin, but not hydrocortisone, treated mice. Further in vitro
      investigations revealed that GLP-2 protected rodent and human 1.1B4 beta-cells
      against streptozotocin induced DNA damage. Furthermore, GLP-2 augmented (P<0.05)
      BRIN BD11 beta-cell proliferation, but was less efficacious in 1.1B4 cells. These
      data highlight the involvement of GLP-2 receptor signalling in the adaptations to
      pancreatic islet cell stress.

PMID- 28746826
TI  - Electrophysiological properties of neurons and synapses in the lateral habenular
      complex (LHb).
AB  - Animal including human behavior is highly sophisticated. Besides reflective
      actions it is largely based on the desire for magnificent internal feelings,
      which are provided by the reward system. Its counterpart an "anti-reward" system
      is mainly composed of the lateral habenular complex (LHb) and its extensive
      interconnections with the monoaminergic cell groups in the mid- and hindbrain.
      The present review focuses on the neuronal composition and the internal signaling
      in the LHb. Morphologically six distinct types of neurons (spherical, fusiform-1,
      fusiform-2, polymorphic, vertical, neurogliaform) can be identified. In contrast,
      setting aside neurogliaform cells, only three broad categories (silent, tonic
      firing, bursting) can be identified using electrophysiological criteria.
      Functionally, LHb neurons express HCN channels and therefore in an "indifferent"
      situation LHb appears to be tonically active. When the situation takes a turn for
      the better habenular cells become inhibited, releasing dopaminergic VTA neurons
      from continuous damping. In contrast, when the situation takes a turn for the
      worse, LHb neurons are stimulated, completely shutting down the activity of
      dopaminergic cells in the VTA.

PMID- 28746827
TI  - Monocyte depletion early after stroke promotes neurogenesis from endogenous
      neural stem cells in adult brain.
AB  - Ischemic stroke, caused by middle cerebral artery occlusion, leads to long
      lasting formation of new striatal neurons from neural stem/progenitor cells
      (NSPCs) in the subventricular zone (SVZ) of adult rodents. Concomitantly with
      this neurogenic response, SVZ exhibits activation of resident microglia and
      infiltrating monocytes. Here we show that depletion of circulating monocytes,
      using the anti-CCR2 antibody MC-21 during the first week after stroke, enhances
      striatal neurogenesis at one week post-insult, most likely by increasing short
      term survival of the newly formed neuroblasts in the SVZ and adjacent striatum.
      Blocking monocyte recruitment did not alter the volume of the ischemic lesion but
      gave rise to reduced astrocyte activation in SVZ and adjacent striatum, which
      could contribute to the improved neuroblast survival. A similar decrease of
      astrocyte activation was found in and around human induced pluripotent stem cell
      (iPSC)-derived NSPCs transplanted into striatum at one week after stroke in
      monocyte-depleted mice. However, there was no effect on neurogenesis in the graft
      as determined 8weeks after implantation. Our findings demonstrate, for the first
      time, that a specific cellular component of the early inflammatory reaction in
      SVZ and adjacent striatum following stroke, i.e., infiltrating monocytes,
      compromises the short-term neurogenic response neurogenesis from endogenous
      NSPCs.

PMID- 28746828
TI  - Asphyxia after complete avalanche burial: A new paradigm.

PMID- 28746829
TI  - Imaging chemistry inside living cells by stimulated Raman scattering microscopy.
AB  - Stimulated Raman scattering (SRS) microscopy is a vibrational imaging platform
      developed to visualize chemical content of a biological sample based on molecular
      vibrational fingerprints. With high-speed, high-sensitivity, and three
      dimensional sectioning capability, SRS microscopy has been used to study chemical
      distribution, molecular transport, and metabolic conversion in living cells in a
      label-free manner. Moreover, aided with bio-orthogonal small-volume Raman probes,
      SRS microscopy allows direct imaging of metabolic activities of small molecules
      in living cells.

PMID- 28746830
TI  - Biophysical characterization of E. coli TolC interaction with the known blocker
      hexaamminecobalt.
AB  - BACKGROUND: The tripartite efflux pump AcrAB-TolC in E. coli is involved in drug
      resistance by transporting antibiotics out of the cell. The outer membrane
      protein TolC can be blocked by various cations, including hexaamminecobalt,
      thereby TolC represents a potential target for reducing antimicrobial resistance
      as its blockage may improve efficacy of antibiotics. METHODS: We utilized single
      channel electrophysiology measurements for studying TolC conductance in the
      absence and presence of the known TolC blocker hexaamminecobalt. Association and
      dissociation constants of hexaamminecobalt were determined using surface plasmon
      resonance measurements. Minimum inhibitory concentration (MIC) assays in the
      absence and presence of antibiotics were carried out for investigating the
      antibacterial effect of hexaamminecobalt and its potential to reduce MICs.
      RESULTS: TolC gating in the absence of any ligand is voltage dependent and
      asymmetric at high applied voltages. Hexaamminecobalt binds to TolC with high
      affinity and kinetic data revealed fast association and dissociation rates.
      Despite potent binding to TolC, hexaamminecobalt does not possess an intrinsic
      antimicrobial activity against E. coli nor does it reduce MIC values of
      antibiotics erythromycin and fusidic acid. CONCLUSIONS: TolC opening can be
      effectively blocked by small molecules. More potent channel blockers are needed
      in order to investigate the eligibility of TolC as drug target. GENERAL
      SIGNIFICANCE: TolC, a potentially interesting pharmaceutical target can be
      addressed by small molecules, blocking the channel. Biophysical characterization
      of the binding processes will support future identification and optimisation of
      more potent TolC blockers in order to validate TolC as a pharmaceutical target.

PMID- 28746831
TI  - Genome-wide analysis of long non-coding RNAs and their role in postnatal porcine
      testis development.
AB  - A comprehensive and systematic understanding of the roles of lncRNAs in the
      postnatal development of the pig testis has still not been achieved. In the
      present study, we obtained more than one billion clean reads and identified
      15,528 lncRNA transcripts; these transcripts included 5032 known and 10,496 novel
      porcine lncRNA transcripts and corresponded to 10,041 lncRNA genes. Pairwise
      comparisons identified 449 known and 324 novel lncRNAs that showed differential
      expression patterns. GO and KEGG pathway enrichment analyses revealed that the
      targeted genes were involved in metabolic pathways regulating testis development
      and spermatogenesis, such as the TGF-beta pathway, the PI3K-Akt pathway, the
      Wnt/beta-catenin pathway, and the AMPK pathway. Using this information, we
      predicted some lncRNAs and coding gene pairs were predicted that may function in
      testis development and spermatogenesis; these are listed in detail. This study
      has provided the most comprehensive catalog to date of lncRNAs in the postnatal
      pig testis and will aid our understanding of their functional roles in testis
      development and spermatogenesis.

PMID- 28746832
TI  - A dual mechanism underlying alpha lateralization in attentional orienting to
      mental representation.
AB  - Numerous electrophysiological findings support the notion that selective
      attention modulates alpha oscillatory activity. Specifically, alpha enhancement
      and suppression can be dissociated in time and space. It is now accepted that
      selective attention operates in either the perceptual or the representational
      environments. Lateralized alpha activity resulting from directing attention to
      mental representations, might arise from a transient alpha desynchronization, as
      recent proposals hypothesized. However, the contribution of enhancement vs
      suppression, as well as their neural correlates to the lateralized alpha
      modulation remain unstudied. To investigate these questions, we recorded
      magnetoencephalography while participants performed a retrospective cueing
      paradigm. Time-frequency analysis revealed a larger transient alpha
      desynchronization for the sensors contralateral to the relevant items which
      originated from the ventral lateral occipital cortex. Additionally, greater
      ipsilateral alpha enhancement in the medial occipital cortex occurred later and
      was maintained until probe presentation. Based on these differences we reasoned
      that the former would reflect the allocation of selective attention to relevant
      items, while the later might signal the inhibition of the irrelevant external
      hemifield instead of irrelevant WM items. Altogether, our results suggest that
      alpha lateralization does not arise from a unitary phenomenon. Dissociated
      anatomical and temporal alpha activity might be signaling different functional
      roles.

PMID- 28746833
TI  - Can an experimental self-efficacy induction through autobiographical recall
      modulate analogue posttraumatic intrusions?
AB  - BACKGROUND AND OBJECTIVES: Research has shown a link between self-efficacy
      appraisals and PTSD symptoms. Less is known about the relation between perceived
      self-efficacy and specific PTSD symptoms such as intrusions. These two
      experiments tested the causal relationship between perceived self-efficacy and
      intrusions from a trauma film. METHODS: In Experiment I, healthy student
      participants received a self-efficacy manipulation consisting of the recall of
      autobiographical memories of success (high self-efficacy condition), failure (low
      self-efficacy condition) or 'important' memories (control condition). Afterwards,
      they viewed a trauma film and recorded their intrusions of the film in the
      following week. In Experiment II the self-efficacy manipulation was given after
      the film. RESULTS: In contrast to expectations, the high self-efficacy condition
      reported a higher number of intrusions relative to the low self-efficacy
      condition in both experiments. LIMITATIONS: The trauma film provides experimental
      control but precludes generalization to real-life trauma. The effect of the
      experimental manipulation was small. The control condition also affected mood and
      confidence. CONCLUSIONS: The results suggest that the relation between self
      efficacy and intrusions development is causal, but not straightforward. Recalling
      personal memories of success before or after a traumatic event may increase the
      risk of developing intrusions, at least under some circumstances. Conversely,
      recalling past failure experiences may be protective, perhaps by preparing the
      individual for adversity, or prompting them to search for coping strategies that
      have been successful in the past. Overall, autobiographical recall involves
      complex processes related to the self that could be useful but need to be more
      fully understood.

PMID- 28746834
TI  - Development of an analytical method for crystalline content determination in
      amorphous solid dispersions produced by hot-melt extrusion using transmission
      Raman spectroscopy: A feasibility study.
AB  - The development of a quantitative method determining the crystalline percentage
      in an amorphous solid dispersion is of great interest in the pharmaceutical
      field. Indeed, the crystalline Active Pharmaceutical Ingredient transformation
      into its amorphous state is increasingly used as it enhances the solubility and
      bioavailability of Biopharmaceutical Classification System class II drugs. One
      way to produce amorphous solid dispersions is the Hot-Melt Extrusion (HME)
      process. This study reported the development and the comparison of the analytical
      performances of two techniques, based on backscattering and transmission Raman
      spectroscopy, determining the crystalline remaining content in amorphous solid
      dispersions produced by HME. Principal Component Analysis (PCA) and Partial Least
      Squares (PLS) regression were performed on preprocessed data and tended towards
      the same conclusions: for the backscattering Raman results, the use of the
      DuoScanTM mode improved the PCA and PLS results, due to a larger analyzed
      sampling volume. For the transmission Raman results, the determination of low
      crystalline percentages was possible and the best regression model was obtained
      using this technique. Indeed, the latter acquired spectra through the whole
      sample volume, in contrast with the previous surface analyses performed using the
      backscattering mode. This study consequently highlighted the importance of the
      analyzed sampling volume.

PMID- 28746835
TI  - Genetic ataxia telangiectasia porcine model phenocopies the multisystemic
      features of the human disease.
AB  - Ataxia telangiectasia (AT) is a progressive multisystem autosomal recessive
      disorder caused by mutations in the AT-mutated (ATM) gene. Early onset AT in
      children is characterized by cerebellar degeneration, leading to motor
      impairment. Lung disease and cancer are the two most common causes of death in AT
      patients. Accelerated thymic involution may contribute to the cancer, and
      recurrent and/or chronic respiratory infections may be a contributing factor to
      lung disease in AT. AT patients have fertility issues, are highly sensitive to
      ionizing radiation and they present oculocutaneous telangiectasia. Current
      treatments only slightly ameliorate disease symptoms; therapy that alters or
      reverses the course of the disease has not yet been discovered. Previously, we
      have shown that ATM-/- pigs, a novel model of AT, present with a loss of Purkinje
      cells, altered cerebellar cytoarchitecture and motor coordination deficits. ATM-/
      porcine model not only recapitulates the neurological phenotype, but also other
      multifaceted clinical features of the human disease. Our current study shows that
      ATM-/- female pigs are infertile, with anatomical and functional signs of an
      immature reproductive system. Both male and female ATM-/- pigs show abnormal
      thymus structure with decreased cell cycle and apoptosis markers in the gland.
      Moreover, ATM-/- pigs have an altered immune system with decreased CD8+ and
      increased natural killer and CD4+CD8+ double-positive cells. Nevertheless, ATM-/-
      pigs manifest a deficient IgG response after a viral infection. Based on the
      neurological and peripheral phenotypes, the ATM-/- pig is a novel genetic model
      that may be used for therapeutic assessments and to identify pathomechanisms of
      this disease.

PMID- 28746836
TI  - A human induced pluripotent stem cell-based in vitro assay predicts developmental
      toxicity through a retinoic acid receptor-mediated pathway for a series of
      related retinoid analogues.
AB  - The relative developmental toxicity potency of a series of retinoid analogues was
      evaluated using a human induced pluripotent stem (iPS) cell assay that measures
      changes in the biomarkers ornithine and cystine. Analogue potency was predicted,
      based on the assay endpoint of the ornithine/cystine (o/c) ratio, to be all-trans
      retinoic acid>TTNPB>13-cis-retinoic acid~9-cis-retinoic
      acid>acitretin>etretinate>retinol. These rankings correlate with in vivo data and
      demonstrate successful application of the assay to rank a series of related toxic
      and non-toxic compounds. The retinoic acid receptor alpha (RARalpha)-selective
      antagonist Ro 41-5253 inhibited the cystine perturbation caused by all-trans
      retinoic acid, TTNPB, 13-cis-retinoic acid, 9-cis-retinoic acid, and acitretin.
      Ornithine was altered independent of RARalpha in all retinoids except acitretin.
      These results suggest a role for an RARalpha-mediated mechanism in retinoid
      induced developmental toxicity through altered cystine metabolism.

PMID- 28746837
TI  - Vitamin D and breast cancer: Past and present.
AB  - The presence of the vitamin D receptor in mammary gland and breast cancer has
      been recognized since the early 1980s, and multiple pre-clinical studies have
      demonstrated that its ligand 1,25D modulates normal mammary gland development and
      sensitivity to carcinogenesis. Although studies have characterized many 1,25D
      responsive targets in normal mammary cells and in breast cancers, validation of
      relevant targets that regulate cell cycle, apoptosis, autophagy and
      differentiation, particularly in vivo, has been challenging. Vitamin D deficiency
      is common in breast cancer patients and some evidence suggests that low vitamin D
      status enhances the risk for disease development or progression. Model systems of
      carcinogenesis have provided evidence that both VDR expression and 1,25D actions
      change with transformation but clinical data regarding vitamin D responsiveness
      of established tumors is limited and inconclusive. Because breast cancer is
      heterogeneous, analysis of VDR actions in specific molecular subtypes of the
      disease is necessary to clarify the conflicting data. Genomic, proteomic and
      metabolomic analyses of in vitro and in vivo model systems is also warranted to
      comprehensively understand the network of vitamin D regulated pathways in the
      context of breast cancer heterogeneity.

PMID- 28746838
TI  - Whole genome characterization of a novel porcine reproductive and respiratory
      syndrome virus 1 isolate: Genetic evidence for recombination between Amervac
      vaccine and circulating strains in mainland China.
AB  - Genotype 1 porcine reproductive and respiratory syndrome virus (PRRSV 1) have
      been continuously isolated in China in recent years. Complete genome sequences of
      these isolates are important to investigate the prevalence and evolution of
      Chinese PRRSV 1. Herein, we describe the isolation of a novel PRRSV 1 isolate,
      denominated HLJB1, in the Heilongjiang province of China. Complete genome
      sequencing of HLJB1 showed that it shares 90.66% and 58.21% nucleotide identities
      with PRRSV 1 and 2 prototypic strains Lelystad virus and ATCC VR-2332,
      respectively. HLJB1 has a unique 5-amino-acid insertion in nsp2, which has never
      been described in other PRRSV 1 isolates. Whole genome-based phylogenetic
      analysis revealed that all Chinese PRRSV 1 isolates are clustered in pan-European
      subtype 1 and can be divided into four subgroups. HLJB1 resides in the subgroup
      of BJEU06-1-like isolates but is also closely related to the Amervac-like
      isolates. Additionally, recombination analyses suggested that HLJB1 is a
      recombinant from the Amervac vaccine and the BJEU06-1 isolate. To our best
      knowledge, our results provide the first genetic evidence for recombination
      between Amervac vaccine and circulating strains. These findings are also
      beneficial for studying the origin and evolution of PRRSV 1 in China.

PMID- 28746839
TI  - Depletion of 5 hydroxy-triptamine (5-HT) affects the antidepressant-like effect
      of neuronal nitric oxide synthase inhibitor in mice.
AB  - Clinical and experimental evidence indicates that nitric oxide (NO) is involved
      in the genesis of depression as well as in antidepressant drug effects.
      Inhibitors of nitric oxide synthases (NOS) exert antidepressant-like effect in
      several animal models, but also interfere with the locomotor activity. The
      involvement of different isoforms of NOS in the antidepressant-like effects is
      not clearly established. The objective of this study was to investigate the
      effects of acute or repeated administration of selective inhibitors of neuronal
      NOS (nNOS) and induced NOS (iNOS), 7 nitroindazole (7NI) and 1400W, respectively,
      in mice subjected to open field (OF) and forced swim test (FST). We also
      investigated if the antidepressant-like effect of nNOS inhibitor, 7NI, was
      dependent on hippocampal serotonin. The results demonstrated that single or
      repeated (3 and 7days) administration of 7NI resulted in antidepressant-like
      effects in mice, evidenced by a significant decrease in immobility time in the
      FST. However, antidepressant-like effects of the iNOS inhibitor, 1400W, were only
      identified after repeated administration for 3 or 7days. The effects of both
      inhibitors were comparable to those obtained with the classical antidepressant
      fluoxetine. It was also demonstrated that the effect of 7NI was dependent of
      hippocampal serotonin. We concluded that inhibition of nNOS and iNOS result in
      antidepressant-like effects, and that these effects hold up after repeated
      administration.

PMID- 28746840
TI  - Quantitative assessments of extracellular EEG to classify specific features of
      main phases of seizure acquisition based on kindling model in Rat.
AB  - OBJECTIVE: Quantitative assessments of extracellular EEG to identify specific
      features of three main phases of seizure acquisition based on kindling model in
      Rat. METHODS: Male rats were divided into 2 groups including kindled (n=10) and
      sham (n=7) and respectively underwent an amygdala rapid kindling and placebo
      kindling. EEG signals in stages 1-2 (initial seizure stages (ISSs)), 3 (localized
      seizure stage (LSS)), and 4-5 generalized seizure stages (GSSs) were divided into
      5 bands: delta (0-4Hz), theta (4-8Hz), alpha (8-12Hz), beta (12-28Hz), and gamma
      (28-40Hz). Spectral power of the sub bands and the ratios of theta/alpha and
      delta/beta were compared in the three phases and between the sham and kindling
      groups. RESULTS: Beta power significantly increased during kindling acquisition,
      though it was significantly lower than sham. Delta oscillation in ISSs was higher
      than LSS and GSSs, but the difference was significant only with LSS. Moreover,
      delta power was higher in all stages of kindling than sham. Gamma power in all
      stages of kindling was significantly lower than sham. Alpha power was
      significantly reduced in ISSs, compared with sham, but gradually increased during
      epileptogenesis. Theta/alpha and delta/beta increased in all stages, compared
      with sham (p<0.05). Theta/alpha significantly decreased in LSS and GSSs, compared
      with ISSs (p<0.05). Delta/beta decreased during kindling, but it was
      significantly different only between ISSs and LSS (P<0.05). CONCLUSION: Beta and
      alpha oscillations at ISSs significantly decreased, but gradually increased along
      with kindling progression. Furthermore, delta power significantly increased
      during kindling process.

PMID- 28746841
TI  - The antidepressant effect of melatonin and fluoxetine in diabetic rats is
      associated with a reduction of the oxidative stress in the prefrontal and
      hippocampal cortices.
AB  - In the past few years possible mechanisms that link diabetes and depression have
      been found. One of these mechanisms is the increase in lipid peroxidation and
      decrease in antioxidant activity in the hippocampal and prefrontal cortices,
      which are brain areas involved in mood. The goal of the present study was to
      evaluate the effect of an antidepressant and of an antioxidant on behavior and
      oxidative activity in brains of diabetic rats. Rats rendered diabetic after a
      treatment with streptozotocin (STZ) (60mg/kg) were treated with fluoxetine
      (15mg/kg), melatonin (10mg/kg), or vehicle for 4 weeks. All animals were tested
      for signs of depression and anxiety using the elevated plus maze (EPM), open
      field test (OFT) and the forced swim test (FST). Four groups were compared: (1)
      normoglycemic, (2) hyperglycemic vehicle treated, and hyperglycemic (3)
      fluoxetine or (4) melatonin treated rats. On the last day of the study, blood
      samples were obtained to determine the levels of hemoglobin A1c (HbA1c). Also,
      brain samples were collected to measure the oxidative stress in the hippocampal
      and prefrontal cortices using the thiobarbituric acid reactive substances (TBARS)
      assay. The activity of the antioxidant enzymes catalase (CAT), glutathione
      peroxidase (GPx), and glutathione S-transferase (GST) were also measured on the
      brain samples. The results show that both fluoxetine and melatonin decrease the
      signs of depression and anxiety in all tests. Concomitantly, the levels of HbA1c
      were reduced in drug treated rats, and to a greater degree in the fluoxetine
      group. In the cerebral cortex of diabetic rats, TBARS was increased, while the
      activity of CAT, GPx and GST were decreased. Fluoxetine and melatonin treatments
      decreased TBARS in both cortices. In the prefrontal cortex, fluoxetine and
      melatonin restored the activity of CAT, while only melatonin improved the
      activity of GPx and GST. In the hippocampus, the activity of GPx alone was
      restored by melatonin, while fluoxetine had no effect. These results suggest that
      antidepressants and antioxidants can counter the mood and oxidative disorders
      associated with diabetes. While these effects could result from a decreased
      production of reactive oxygen species (ROS) remains to be established.

PMID- 28746842
TI  - The droso4schools project: Long-term scientist-teacher collaborations to promote
      science communication and education in schools.
AB  - Science communication is becoming an increasingly important part of a scientist's
      remit, and engaging with primary and secondary schools is one frequently chosen
      strategy. Here we argue that science communication in schools will be more
      effective if based on good understanding of the realities of school life, which
      can be achieved through structured participation and/or collaboration with
      teachers. For example, the Manchester Fly Facility advocates the use of the fruit
      fly Drosophila as an important research strategy for the discovery processes in
      the biomedical sciences. To communicate this concept also in schools, we
      developed the 'droso4schools' project as a refined form of scientist-teacher
      collaboration that embraces the expertise and interests of teachers. Within this
      project, we place university students as teaching assistants in university
      partner schools to collaborate with teachers and develop biology lessons with
      adjunct support materials. These lessons teach curriculum-relevant biology topics
      by making use of the profound conceptual understanding existing in Drosophila
      combined with parallel examples taken from human biology. By performing easy to
      implement experiments with flies, we bring living organisms into these lessons,
      thus endeavouring to further enhance the pupil's learning experience. In this
      way, we do not talk about flies but rather work with flies as powerful teaching
      tools to convey mainstream curriculum biology content, whilst also bringing
      across the relevance of Drosophila research. Through making these lessons freely
      available online, they have the potential to reach out to teachers and scientists
      worldwide. In this paper, we share our experiences and strategies to provide
      ideas for scientists engaging with schools, including the application of the
      droso4schools project as a paradigm for long-term school engagement which can be
      adapted also to other areas of science.

PMID- 28746843
TI  - The role of the microenvironment in the biophysics of cancer.
AB  - During the last decades, cell mechanics has been recognized as a quantitative
      measure to discriminate between many physiological and pathological states of
      single cells. In the field of biophysics of cancer, a large body of research has
      been focused on the comparison between normal and cancer mechanics and slowly the
      hypothesis that cancer cells are softer than their normal counterparts has been
      accepted, even though in situ tumor tissue is usually stiffer than the
      surrounding normal tissue. This corroborates the idea that the extra-cellular
      matrix (ECM) has a critical role in regulating tumor cell properties and
      behavior. Rearrangements in ECM can lead to changes in cancer cell mechanics and
      in specific conditions the general assumption about cancer cell softening could
      be confuted. Here, we highlight the contribution of ECM in cancer cell mechanics
      and argue that the statement that cancer cells are softer than normal cells
      should be firmly related to the properties of cell environment and the specific
      stage of cancer cell progression. In particular, we will discuss that when
      employing cell mechanics in cancer diagnosis and discrimination, the chemical,
      the topographical and - last but not least - the mechanical properties of the
      microenvironment are very important.

PMID- 28746844
TI  - Heart rate variability reveals that a decrease in parasympathetic ('rest-and
      digest') activity dominates autonomic stress responses in a free-living seabird.
AB  - The autonomic stress response, often referred to as the 'fight-or-flight'
      response, is a highly conserved physiological reaction to stress in vertebrates
      that occurs via a decrease in parasympathetic (PNS) activity, which promotes self
      maintenance 'rest and digest' processes, and an increase in sympathetic (SNS)
      activity, which prepares an animal for danger ('fight-or-flight'). Though the PNS
      and SNS both innervate most organs, they often control different tissues and
      functions within those organs (though the pacemaker of the heart is controlled by
      both). Moreover the PNS and SNS are regulated independently. Yet until now, most
      studies of autonomic stress responses in non-model species focused only on the
      SNS response. We used external electrocardiogram loggers to measure heart rate
      and heart rate variability indexes that reflect PNS and SNS activity in a
      seabird, the Streaked Shearwater (Calonectris leucomelas), during the stress of
      handling, and during recovery in the nest burrow or during restraint in a cloth
      bag. We show for the first time in a free-living animal that the autonomic stress
      response is mediated primarily by a rapid decrease in PNS activity: handling
      stress induced a large and long-lasting depression of PNS 'rest-and-digest'
      activity that required two hours to recover. We also found evidence for a
      substantially smaller and shorter-lasting SNS 'fight-or-flight' response.
      Confinement in a cloth bag was less stressful for birds than handling, but more
      stressful than recovering in nest burrows. We show that quantifying autonomic
      activity from heart rate variability is effective for non-invasively studying
      stress physiology in free-living animals.

PMID- 28746845
TI  - Cooperation between Magnesium and Metabolite Controls Collapse of the SAM-I
      Riboswitch.
AB  - The S-adenosylmethionine (SAM)-I riboswitch is a noncoding RNA that regulates the
      transcription termination process in response to metabolite (SAM) binding. The
      aptamer portion of the riboswitch may adopt an open or closed state depending on
      the presence of metabolite. Although the transition between the open and closed
      states is critical for the switching process, its atomistic details are not well
      understood. Using atomistic simulations, we calculate the effect of SAM and
      magnesium ions on the folding free energy landscape of the SAM-I riboswitch.
      These molecular simulation results are consistent with our previous wetlab
      experiments and aid in interpreting the SHAPE probing measurements. Here,
      molecular dynamics simulations explicitly identify target RNA motifs sensitive to
      magnesium ions and SAM. In the simulations, we observe that, whereas the
      metabolite mostly stabilizes the P1 and P3 helices, magnesium serves an important
      role in stabilizing a pseudoknot interaction between the P2 and P4 helices, even
      at high metabolite concentrations. The pseudoknot stabilization by magnesium, in
      combination with P1 stabilization by SAM, explains the requirement of both SAM
      and magnesium to form the fully collapsed metabolite-bound closed state of the
      SAM-I riboswitch. In the absence of SAM, frequent open-to-closed conformational
      transitions of the pseudoknot occur, akin to breathing. These pseudoknot
      fluctuations disrupt the binding site by facilitating fluctuations in the 5'-end
      of helix P1. Magnesium biases the landscape toward a collapsed state
      (preorganization) by coordinating pseudoknot and 5'-P1 fluctuations. The
      cooperation between SAM and magnesium in stabilizing important tertiary
      interactions elucidates their functional significance in transcription
      regulation.

PMID- 28746846
TI  - Relieving the Pressure on Tissue Development.

PMID- 28746847
TI  - Thermodynamic Bounds on the Ultra- and Infra-affinity of Hsp70 for Its
      Substrates.
AB  - The 70 kDa heat shock protein Hsp70 has several essential functions in living
      systems, such as protecting cells against protein aggregation, assisting protein
      folding, remodeling protein complexes, and driving translocation into organelles.
      These functions require high affinity for nonspecific amino acid sequences that
      are ubiquitous in proteins. It has been recently shown that this high affinity,
      called ultra-affinity, depends on a process driven out of equilibrium by ATP
      hydrolysis. Here, we establish the thermodynamic bounds for ultra-affinity, and
      further show that the same reaction scheme can in principle be used both to
      strengthen and to weaken affinities (leading in this case to infra-affinity). We
      show that cofactors are essential to achieve affinity beyond the equilibrium
      range. Finally, biological implications are discussed.

PMID- 28746848
TI  - Natural Conformational Sampling of Human TNFalpha Visualized by Double Electron
      Electron Resonance.
AB  - Double electron-electron resonance in conjunction with site-directed spin
      labeling has been used to probe natural conformational sampling of the human
      tumor necrosis factor alpha trimer. We suggest a previously unreported,
      predeoligomerization conformation of the trimer that has been shown to be sampled
      at low frequency. A model of this trimeric state has been constructed based on
      crystal structures using the double-electron-electron-resonance distances. The
      model shows one of the protomers to be rotated and tilted outward at the tip end,
      leading to a breaking of the trimerous symmetry and distortion at a receptor
      binding interface. The new structure offers opportunities to modulate the
      biological activity of tumor necrosis factor alpha through stabilization of the
      distorted trimer with small molecules.

PMID- 28746849
TI  - Death Receptor 5 Activation Is Energetically Coupled to Opening of the
      Transmembrane Domain Dimer.
AB  - The precise mechanism by which binding of tumor necrosis factor ligands to the
      extracellular domain of their corresponding receptors transmits signals across
      the plasma membrane has remained elusive. Recent studies have proposed that
      activation of several tumor necrosis factor receptors, including Death Receptor
      5, involves a scissorlike opening of the disulfide-linked transmembrane (TM)
      dimer. Using time-resolved fluorescence resonance energy transfer, we provide, to
      our knowledge, the first direct biophysical evidence that Death Receptor 5 TM
      dimers open in response to ligand binding. Then, to probe the importance of the
      closed-to-open TM domain transition in the overall energetics of receptor
      activation, we designed point-mutants (alanine to phenylalanine) in the
      predicted, tightly packed TM domain dimer interface. We hypothesized that the
      bulky residues should destabilize the closed conformation and eliminate the ~3
      kcal/mol energy barrier to TM domain opening and the ~2 kcal/mol energy
      difference between the closed and open states, thus oversensitizing the receptor.
      To test this, we used all-atom molecular dynamics simulations of the isolated TM
      domain in explicit lipid bilayers coupled to thermodynamic potential of mean
      force calculations. We showed that single point mutants at the interface altered
      the energy landscape as predicted, but were not enough to completely eliminate
      the barrier to opening. However, the computational model did predict that a
      double mutation at i, i+4 positions at the center of the TM domain dimer
      eliminates the barrier and stabilizes the open conformation relative to the
      closed. We tested these mutants in cells with time-resolved fluorescence
      resonance energy transfer and death assays, and show remarkable agreement with
      the calculations. The single mutants had a small effect on TM domain separation
      and cell death, whereas the double mutant significantly increased the TM domain
      separation and more than doubled the sensitivity of cells to ligand stimulation.

PMID- 28746850
TI  - Investigation of N-Terminal Phospho-Regulation of Uracil DNA Glycosylase Using
      Protein Semisynthesis.
AB  - Uracil DNA Glycosylase (UNG2) is the primary enzyme in humans that prevents the
      stable incorporation of deoxyuridine monophosphate into DNA in the form of U/A
      basepairs. During S-phase, UNG2 remains associated with the replication fork
      through its interactions with two proteins, Proliferating Cell Nuclear Antigen
      (PCNA) and Replication Protein A (RPA), which are critical for DNA replication
      and repair. In this work, we used protein semisynthesis and fluorescence
      anisotropy assays to explore the interactions of UNG2 with PCNA and RPA and to
      determine the effects of two UNG2 phosphorylation sites (Thr6 and Tyr8) located
      within its PCNA-interacting motif (PIP-box). In binding assays, we found that
      phosphorylation of Thr6 or Tyr8 on UNG2 can impede PCNA binding without affecting
      UNG2 catalytic activity or its RPA interaction. Our data also suggests that
      unmodified UNG2, PCNA, and RPA can form a ternary protein complex. We propose
      that the UNG2 N-terminus may serve as a flexible scaffold to tether PCNA and RPA
      at the replication fork, and that post-translational modifications on the UNG2 N
      terminus disrupt formation of the PCNA-UNG2-RPA protein complex.

PMID- 28746851
TI  - The Unique Protein-to-Protein Carotenoid Transfer Mechanism.
AB  - Orange Carotenoid Protein (OCP) is known as an effector and regulator of
      cyanobacterial photoprotection. This 35 kDa water-soluble protein provides
      specific environment for blue-green light absorbing keto-carotenoids, which
      excitation causes dramatic but fully reversible rearrangements of the OCP
      structure, including carotenoid translocation and separation of C- and N-terminal
      domains upon transition from the basic orange to photoactivated red OCP form.
      Although recent studies greatly improved our understanding of the OCP photocycle
      and interaction with phycobilisomes and the fluorescence recovery protein, the
      mechanism of OCP assembly remains unclear. Apparently, this process requires
      targeted delivery and incorporation of a highly hydrophobic carotenoid molecule
      into the water-soluble apoprotein of OCP. Recently, we introduced, to our
      knowledge, a novel carotenoid carrier protein, COCP, which consists of dimerized
      C-domain(s) of OCP and can combine with the isolated N-domain to form transient
      OCP-like species. Here, we demonstrate that in vitro COCP efficiently transfers
      otherwise tightly bound carotenoid to the full-length OCP apoprotein, resulting
      in formation of photoactive OCP from completely photoinactive species. We
      accurately analyze the peculiarities of this process that, to the best of our
      knowledge, appears unique, a previously uncharacterized protein-to-protein
      carotenoid transfer mechanism. We hypothesize that a similar OCP assembly can
      occur in vivo, substantiating specific roles of the COCP carotenoid carrier in
      cyanobacterial photoprotection.

PMID- 28746852
TI  - Photo-Cross-Linking of IKs Demonstrates State-Dependent Interactions between
      KCNE1 and KCNQ1.
AB  - The slow delayed rectifier potassium current (IKs) is a key repolarizing current
      during the cardiac action potential. It consists of four KCNQ1 alpha-subunits and
      up to four KCNE1 beta-subunits, which are thought to reside within external
      clefts of the channel. The interaction of KCNE1 with KCNQ1 dramatically delays
      opening of the channel but the mechanisms by which this occur are not yet fully
      understood. Here, we have used unnatural amino acid photo-cross-linking to
      investigate the dynamic interactions that occur between KCNQ1 and KCNE1 during
      activation gating. The unnatural amino acid p-Benzoylphenylalanine was
      successfully incorporated into two residues within the transmembrane domain of
      KCNE1: F56 and F57. UV-induced cross-linking suggested that F56Bpa interacts with
      KCNQ1 in the open state, whereas F57Bpa interacts predominantly in resting
      channel conformations. When UV was applied at progressively more depolarized
      preopen holding potentials, cross-linking of F57Bpa with KCNQ1 was slowed, which
      indicates that KCNE1 is displaced within the channel's cleft early during
      activation, or that conformational changes in KCNQ1 alter its interaction with
      KCNE1. In E1R/R4E KCNQ1, a mutant with constitutively activated voltage sensors,
      F56Bpa and F57Bpa KCNE1 were cross-linked in open and closed states,
      respectively, which suggests that their actions are mediated mainly by modulation
      of KCNQ1 pore function.

PMID- 28746853
TI  - Ions Modulate Stress-Induced Nanotexture in Supported Fluid Lipid Bilayers.
AB  - Most plasma membranes comprise a large number of different molecules including
      lipids and proteins. In the standard fluid mosaic model, the membrane function is
      effected by proteins whereas lipids are largely passive and serve solely in the
      membrane cohesion. Here we show, using supported 1,2-dioleoyl-sn-glycero-3
      phosphocholine lipid bilayers in different saline solutions, that ions can
      locally induce ordering of the lipid molecules within the otherwise fluid bilayer
      when the latter is supported. This nanoordering exhibits a characteristic length
      scale of ~20 nm, and manifests itself clearly when mechanical stress is applied
      to the membrane. Atomic force microscopy (AFM) measurements in aqueous solutions
      containing NaCl, KCl, CaCl2, and Tris buffer show that the magnitude of the
      effect is strongly ion-specific, with Ca2+ and Tris, respectively, promoting and
      reducing stress-induced nanotexturing of the membrane. The AFM results are
      complemented by fluorescence recovery after photobleaching experiments, which
      reveal an inverse correlation between the tendency for molecular nanoordering and
      the diffusion coefficient within the bilayer. Control AFM experiments on other
      lipids and at different temperatures support the hypothesis that the
      nanotexturing is induced by reversible, localized gel-like solidification of the
      membrane. These results suggest that supported fluid phospholipid bilayers are
      not homogenous at the nanoscale, but specific ions are able to locally alter
      molecular organization and mobility, and spatially modulate the membrane's
      properties on a length scale of ~20 nm. To illustrate this point, AFM was used to
      follow the adsorption of the membrane-penetrating antimicrobial peptide Temporin
      L in different solutions. The results confirm that the peptides do not absorb
      randomly, but follow the ion-induced spatial modulation of the membrane. Our
      results suggest that ionic effects have a significant impact for passively
      modulating the local properties of biological membranes, when in contact with a
      support such as the cytoskeleton.

PMID- 28746854
TI  - Effect of Hydrodynamic Interactions on Reaction Rates in Membranes.
AB  - The Brownian motion of two particles in three dimensions serves as a model for
      predicting the diffusion-limited reaction rate, as first discussed by von
      Smoluchowski. Deutch and Felderhof extended the calculation to account for
      hydrodynamic interactions between the particles and the target, which results in
      a reduction of the rate coefficient by about half. Many chemical reactions take
      place in quasi-two-dimensional systems, such as on the membrane or surface of a
      cell. We perform a Smoluchowski-like calculation in a quasi-two-dimensional
      geometry, i.e., a membrane surrounded by fluid, and account for hydrodynamic
      interactions between the particles. We show that rate coefficients are reduced
      relative to the case of no interactions. The reduction is more pronounced than
      the three-dimensional case due to the long-range nature of two-dimensional flows.

PMID- 28746855
TI  - A Versatile Framework for Simulating the Dynamic Mechanical Structure of
      Cytoskeletal Networks.
AB  - Computer simulations can aid in understanding how collective materials properties
      emerge from interactions between simple constituents. Here, we introduce a coarse
      grained model that enables simulation of networks of actin filaments, myosin
      motors, and cross-linking proteins at biologically relevant time and length
      scales. We demonstrate that the model qualitatively and quantitatively captures a
      suite of trends observed experimentally, including the statistics of filament
      fluctuations, and mechanical responses to shear, motor motilities, and network
      rearrangements. We use the simulation to predict the viscoelastic scaling
      behavior of cross-linked actin networks, characterize the trajectories of actin
      in a myosin motility assay, and develop order parameters to measure contractility
      of a simulated actin network. The model can thus serve as a platform for
      interpretation and design of cytoskeletal materials experiments, as well as for
      further development of simulations incorporating active elements.

PMID- 28746856
TI  - Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in
      Actin Polymerization.
AB  - Formins are force-sensing proteins that regulate actin polymerization dynamics.
      Here, we applied stretching tension to individual actin filaments under the
      regulation of formin mDia1 to investigate the mechanical responses in actin
      polymerization dynamics. We found that the elongation of an actin filament was
      accelerated to a greater degree by stretching tension for ADP-G-actin than that
      for ATP-G-actin. An apparent decrease in the critical concentration of G-actin
      was observed, especially in ADP-G-actin. These results on two types of G-actin
      were reproduced by a simple kinetic model, assuming the rapid equilibrium between
      pre- and posttranslocated states of the formin homology domain two dimer. In
      addition, profilin concentration dramatically altered the force-dependent
      acceleration of actin filament elongation, which ranged from twofold to an all-or
      none response. Even under conditions in which actin depolymerization occurred,
      applications of a several-piconewton stretching tension triggered rapid actin
      filament elongation. This extremely high force-sensing mechanism of mDia1 and
      profilin could be explained by the force-dependent coordination of the biphasic
      effect of profilin; i.e., an acceleration effect masked by a depolymerization
      effect became dominant under stretching tension, negating the latter to rapidly
      enhance the elongation rate. Our findings demonstrate that the biphasic effect of
      profilin is controlled by mechanical force, thus expanding the function of mDia1
      as a mechanosensitive regulator of actin polymerization.

PMID- 28746857
TI  - Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a
      Molecular Adjuvant.
AB  - Pulsed electric fields applied to cells have been used as an invaluable research
      tool to enhance delivery of genes or other intracellular cargo, as well as for
      tumor treatment via electrochemotherapy or tissue ablation. These processes
      involve the buildup of charge across the cell membrane, with subsequent
      alteration of transmembrane potential that is a function of cell biophysics and
      geometry. For traditional electroporation parameters, larger cells experience a
      greater degree of membrane potential alteration. However, we have recently
      demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a
      key predictor of response for cells treated with high-frequency irreversible
      electroporation (IRE). In this study, we leverage a targeted molecular therapy,
      ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2
      receptor, to investigate how biophysical cellular changes resulting from NCR
      manipulation affect the response to IRE at varying frequencies. We present
      evidence that the increase in the NCR mitigates the cell death response to
      conventional electroporation pulsed-electric fields (~100 MUs), consistent with
      the previously noted size dependence. However, this same molecular treatment
      enhanced the cell death response to high-frequency electric fields (~1 MUs). This
      finding demonstrates the importance of considering cellular biophysics and
      frequency-dependent effects in developing electroporation protocols, and our
      approach provides, to our knowledge, a novel and direct experimental methodology
      to quantify the relationship between cell morphology, pulse frequency, and
      electroporation response. Finally, this novel, to our knowledge, combinatorial
      approach may provide a paradigm to enhance in vivo tumor ablation through a
      molecular manipulation of cellular morphology before IRE application.

PMID- 28746858
TI  - Modeling of Biomechanics and Biorheology of Red Blood Cells in Type 2 Diabetes
      Mellitus.
AB  - Erythrocytes in patients with type-2 diabetes mellitus (T2DM) are associated with
      reduced cell deformability and elevated blood viscosity, which contribute to
      impaired blood flow and other pathophysiological aspects of diabetes-related
      vascular complications. In this study, by using a two-component red blood cell
      (RBC) model and systematic parameter variation, we perform detailed computational
      simulations to probe the alteration of the biomechanical, rheological, and
      dynamic behavior of T2DM RBCs in response to morphological change and membrane
      stiffening. First, we examine the elastic response of T2DM RBCs subject to static
      tensile forcing and their viscoelastic relaxation response upon release of the
      stretching force. Second, we investigate the membrane fluctuations of T2DM RBCs
      and explore the effect of cell shape on the fluctuation amplitudes. Third, we
      subject the T2DM RBCs to shear flow and probe the effects of cell shape and
      effective membrane viscosity on their tank-treading movement. In addition, we
      model the cell dynamic behavior in a microfluidic channel with constriction and
      quantify the biorheological properties of individual T2DM RBCs. Finally, we
      simulate T2DM RBC suspensions under shear and compare the predicted viscosity
      with experimental measurements. Taken together, these simulation results and
      their comparison with currently available experimental data are helpful in
      identifying a specific parametric model-the first of its kind, to our knowledge
      that best describes the main hallmarks of T2DM RBCs, which can be used in future
      simulation studies of hematologic complications of T2DM patients.

PMID- 28746859
TI  - Release of Applied Mechanical Loading Stimulates Intercellular Calcium Waves in
      Drosophila Wing Discs.
AB  - Mechanical forces are critical but poorly understood inputs for organogenesis and
      wound healing. Calcium ions (Ca2+) are critical second messengers in cells for
      integrating environmental and mechanical cues, but the regulation of Ca2+
      signaling is poorly understood in developing epithelial tissues. Here we report a
      chip-based regulated environment for microorgans that enables systematic
      investigations of the crosstalk between an organ's mechanical stress environment
      and biochemical signaling under genetic and chemical perturbations. This method
      enabled us to define the essential conditions for generating organ-scale
      intercellular Ca2+ waves in Drosophila wing discs that are also observed in vivo
      during organ development. We discovered that mechanically induced intercellular
      Ca2+ waves require fly extract growth serum as a chemical stimulus. Using the
      chip-based regulated environment for microorgans, we demonstrate that not the
      initial application but instead the release of mechanical loading is sufficient,
      but not necessary, to initiate intercellular Ca2+ waves. The Ca2+ response
      depends on the prestress intercellular Ca2+ activity and not on the magnitude or
      duration of the mechanical stimulation applied. Mechanically induced
      intercellular Ca2+ waves rely on IP3R-mediated Ca2+-induced Ca2+ release and
      propagation through gap junctions. Thus, intercellular Ca2+ waves in developing
      epithelia may be a consequence of stress dissipation during organ growth.

PMID- 28746861
TI  - Investigation of the inhibitory potential of phospholipase A2 inhibitor gamma
      from Sinonatrix annularis to snake envenomation.
AB  - SaPLIgamma is a novel gamma phospholipase A2 inhibitor (PLI) recently isolated
      from Sinonatrix annularis, a Chinese endemic non-venomous snake. To explore the
      neutralization effects of saPLIgamma in snakebite envenomation, a dose equivalent
      to LD50 of Deinagkistrodon acutus, Agkistrodon halys and Naja atra venom
      with/without saPLIgamma was inoculated into the gastrocnemius muscle of female
      Kunming mice. The ability of saPLIgamma to inhibit myonecrosis and systemic
      toxicity were evaluated through investigations of muscle histopathology, and
      determination of the serum levels of creatine kinase (CK), lactate dehydrogenase
      isoenzyme1 (LDH1) and aspartate transferase (AST). Edema of the gastrocnemius
      muscle was evaluated by calculating the width difference between the inoculated
      limb and the contralateral leg. Desmin loss in the gastrocnemius muscle was
      determined by Western blot analysis. Co-immunoprecipitation and shotgun LC-MS/MS
      analyses were performed to identify venom proteins that interact with saPLIgamma.
      All the envenomed mice had significantly elevated serum CK, LDH1 and AST levels,
      whereas the levels were decreased significantly in the presence of saPLIgamma.
      Histopathological evaluation of gastrocnemius muscle sections showed severe snake
      venom-induced damage, characterized by leukocyte infiltration and erythrocyte
      leakage, leading to local edema. Myonecrosis, hemorrhage and desmin loss were
      significantly attenuated by saPLIgamma. SaPLIgamma interacted with a wide range
      of venom proteins, including PLA2s, metalloproteinases and C type lectins, which
      may contribute to broad anti-venom effects.

PMID- 28746860
TI  - Integrating RNA sequencing into neuro-oncology practice.
AB  - Malignant tumors of the central nervous system (CNS) cause substantial morbidity
      and mortality, yet efforts to optimize chemo- and radiotherapy have largely
      failed to improve dismal prognoses. Over the past decade, RNA sequencing (RNA
      seq) has emerged as a powerful tool to comprehensively characterize the
      transcriptome of CNS tumor cells in one high-throughput step, leading to improved
      understanding of CNS tumor biology and suggesting new routes for targeted
      therapies. RNA-seq has been instrumental in improving the diagnostic
      classification of brain tumors, characterizing oncogenic fusion genes, and
      shedding light on intratumor heterogeneity. Currently, RNA-seq is beginning to be
      incorporated into regular neuro-oncology practice in the form of precision neuro
      oncology programs, which use information from tumor sequencing to guide
      implementation of personalized targeted therapies. These programs show great
      promise in improving patient outcomes for tumors where single agent trials have
      been ineffective. As RNA-seq is a relatively new technique, many further
      applications yielding new advances in CNS tumor research and management are
      expected in the coming years.

PMID- 28746862
TI  - Generation of monoclonal antibodies and development of an immunofluorometric
      assay for the detection of CUZD1 in tissues and biological fluids.
AB  - BACKGROUND: CUB and zona pellucida-like domain-containing protein 1 (CUZD1) was
      identified as a pancreas-specific protein and was proposed as a candidate
      biomarker for pancreatic related disorders. CUZD1 protein levels in tissues and
      biological fluids have not been extensively examined. The purpose of the present
      study was to generate specific antibodies targeting CUZD1 to assess CUZD1
      expression within tissues and biological fluids. METHODS: Mouse monoclonal
      antibodies against CUZD1 were generated and used to perform immunohistochemical
      analyses and to develop a sensitive and specific enzyme-linked immunosorbent
      assay (ELISA). CUZD1 protein expression was assessed in various human tissue
      extracts and biological fluids and in gel filtration chromatography-derived
      fractions of pancreatic tissue extract, pancreatic juice and recombinant protein.
      RESULTS: Immunohistochemical staining of CUZD1 in pancreatic tissue showed that
      the protein is localized to the acinar cells and the lumen of the acini. Western
      blot analysis detected the protein in pancreatic tissue extract and pancreatic
      juice. The newly developed ELISA measured CUZD1 in high levels in pancreas and in
      much lower but detectable levels in several other tissues. In the biological
      fluids tested, CUZD1 expression was detected exclusively in pancreatic juice. The
      analysis of gel filtration chromatography-derived fractions of pancreatic tissue
      extract, pancreatic juice and recombinant CUZD1 suggested that the protein exists
      in high molecular weight protein complexes. CONCLUSION: This study describes the
      development of tools targeting CUZD1 protein, its tissue expression pattern and
      levels in several biological fluids. These new tools will facilitate future
      investigations aiming to delineate the role of CUZD1 in physiology and
      pathobiology.

PMID- 28746863
TI  - Cortical Interneurons Differentially Regulate the Effects of Acoustic Context.
AB  - Both behavioral and neural responses to sounds are generally modified by the
      acoustic context in which they are encountered. As an example, in the auditory
      cortex, preceding sounds can powerfully suppress responses to later, spectrally
      similar sounds-a phenomenon called forward suppression (FWS). Whether cortical
      inhibitory networks shape such suppression or whether it is wholly regulated by
      common mechanisms such as synaptic depression or spike frequency adaptation is
      controversial. Here, we show that optogenetically suppressing somatostatin
      positive (Sst+) interneurons weakens forward suppression, often revealing
      facilitation in neurons that are normally forward-suppressed. In contrast,
      inactivating parvalbumin-positive (Pvalb+) interneurons strengthens forward
      suppression and alters its frequency dependence. In a simple network model, we
      show that these effects can be accounted for by differences in short-term
      synaptic dynamics of inputs onto Pvalb+ and Sst+ interneurons. These results
      demonstrate separate roles for somatostatin and parvalbumin interneurons in
      regulating the context dependence of auditory processing.

PMID- 28746864
TI  - The Lifespan and Turnover of Microglia in the Human Brain.
AB  - The hematopoietic system seeds the CNS with microglial progenitor cells during
      the fetal period, but the subsequent cell generation dynamics and maintenance of
      this population have been poorly understood. We report that microglia, unlike
      most other hematopoietic lineages, renew slowly at a median rate of 28% per year,
      and some microglia last for more than two decades. Furthermore, we find no
      evidence for the existence of a substantial population of quiescent long-lived
      cells, meaning that the microglia population in the human brain is sustained by
      continuous slow turnover throughout adult life.

PMID- 28746865
TI  - Polycomb Responds to Low Levels of Transcription.
AB  - How is Polycomb (Pc), a eukaryotic negative regulator of transcription, targeted
      to specific mammalian genes? Our genome-wide analysis of the Pc mark H3K27me3 in
      murine cells revealed that Pc is preferentially associated with CpG island
      promoters of genes that are transcribed at a low level and less so with promoters
      of genes that are either silent or more highly expressed. Studies of the CpG
      island promoter of the Kit gene demonstrate that Pc is largely absent when the
      gene is silent in myeloid cells, as well as when the gene is highly expressed in
      mast cells. Manipulations that increase transcription in the former case, and
      reduce it in the latter, increase Pc occupancy. The average negative effect of
      Pc, we infer, is about 2-fold. We suggest possible biological roles for such
      negative effects and propose a mechanism by which Pc might be recruited to weakly
      transcribed genes.

PMID- 28746866
TI  - AIM2 Engages Active but Unprocessed Caspase-1 to Induce Noncanonical Activation
      of the NLRP3 Inflammasome.
AB  - Inflammasomes are multimeric protein complexes that initiate inflammatory
      cascades. Their activation is a hallmark of many infectious or inflammatory
      diseases. Their composition and activity are specified by proinflammatory
      stimuli. For example, the NLRP3 inflammasome is activated in response to cell
      damage and K+ efflux, whereas the AIM2 inflammasome is activated in response to
      cytosolic DNA. We used Legionella pneumophila, an intracellular bacterial
      pathogen that activates multiple inflammasomes, to elucidate the molecular
      mechanisms regulating inflammasome activation during infection. Upon infection,
      the AIM2 inflammasome engaged caspase-1 to induce pore formation in the cell
      membrane, which then caused K+-efflux-mediated activation of NLRP3. Thus, the
      AIM2 inflammasome amplifies signals of infection, triggering noncanonical
      activation of NLRP3. During infection, AIM2 and caspase-11 induced membrane
      damage, which was sufficient and essential for activating the NLRP3 inflammasome.
      Our data reveal that different inflammasomes regulate one another's activity to
      ensure an effective immune response to infection.

PMID- 28746867
TI  - TCR Signal Quality Modulates Fate Decisions of Single CD4+ T Cells in a
      Probabilistic Manner.
AB  - To what extent the lineage decisions of activated CD4+ T cells are determined by
      the quality of T cell receptor (TCR) ligation is incompletely understood. Here,
      we show that individual T cells expressing identical TCRs take highly variable
      fate decisions despite binding the same ligand. We identify a mathematical model
      that correctly captures this probabilistic behavior and allows one to formalize
      changes in TCR signal quality-due to cognate versus altered peptide ligation-as
      changes of lineage-specific proliferation and differentiation rates. We show that
      recall responses also adhere to this probabilistic framework requiring
      recruitment of multiple memory clones to provide reliable differentiation
      patterns. By extending our framework to simulate hypothetical TCRs of distinct
      binding strength, we reconstruct primary and secondary response patterns emerging
      from a polyclonal TCR repertoire in silico. Collectively, these data suggest that
      individual T cells harboring distinct TCRs generate overlapping primary
      differentiation patterns that segregate only upon repetitive immunization.

PMID- 28746868
TI  - DDX6 Represses Aberrant Activation of Interferon-Stimulated Genes.
AB  - The innate immune system tightly regulates activation of interferon-stimulated
      genes (ISGs) to avoid inappropriate expression. Pathological ISG activation
      resulting from aberrant nucleic acid metabolism has been implicated in autoimmune
      disease; however, the mechanisms governing ISG suppression are unknown. Through a
      genome-wide genetic screen, we identified DEAD-box helicase 6 (DDX6) as a
      suppressor of ISGs. Genetic ablation of DDX6 induced global upregulation of ISGs
      and other immune genes. ISG upregulation proved cell intrinsic, imposing an
      antiviral state and making cells refractory to divergent families of RNA viruses.
      Epistatic analysis revealed that ISG activation could not be overcome by deletion
      of canonical RNA sensors. However, DDX6 deficiency was suppressed by disrupting
      LSM1, a core component of mRNA degradation machinery, suggesting that
      dysregulation of RNA processing underlies ISG activation in the DDX6 mutant. DDX6
      is distinct among DExD/H helicases that regulate the antiviral response in its
      singular ability to negatively regulate immunity.

PMID- 28746869
TI  - Cytosolic Pellino-1-Mediated K63-Linked Ubiquitination of IRF5 in M1 Macrophages
      Regulates Glucose Intolerance in Obesity.
AB  - IRF5 is a signature transcription factor that induces M1 macrophage polarization.
      However, little is known regarding cytosolic proteins that induce IRF5 activation
      for M1 polarization. Here, we report the interaction between ubiquitin E3 ligase
      Pellino-1 and IRF5 in the cytoplasm, which increased nuclear translocation of
      IRF5 by K63-linked ubiquitination in human and mouse M1 macrophages. LPS and/or
      IFN-gamma increased Pellino-1 expression, and M1 polarization was attenuated in
      Pellino-1-deficient macrophages in vitro and in vivo. Defective M1 polarization
      in Pellino-1-deficient macrophages improved glucose intolerance in mice fed a
      high-fat diet. Furthermore, macrophages in adipose tissues from obese humans
      exhibited increased Pellino-1 expression and IRF5 nuclear translocation compared
      with nonobese subjects, and these changes are associated with insulin resistance
      index. This study demonstrates that cytosolic Pellino-1-mediated K63-linked
      ubiquitination of IRF5 in M1 macrophages regulates glucose intolerance in
      obesity, suggesting a cytosolic mediator function of Pellino-1 in TLR4/IFN-gamma
      receptor-IRF5 axis during M1 polarization.

PMID- 28746870
TI  - Identification of a Genetic Variation in ERAP1 Aminopeptidase that Prevents Human
      Cytomegalovirus miR-UL112-5p-Mediated Immunoevasion.
AB  - Herein, we demonstrate that HCMV miR-UL112-5p targets ERAP1, thereby inhibiting
      the processing and presentation of the HCMV pp65495-503 peptide to specific CTLs.
      In addition, we show that the rs17481334 G variant, naturally occurring in the
      ERAP1 3' UTR, preserves ERAP1 from miR-UL112-5p-mediated degradation.
      Specifically, HCMV miR-UL112-5p binds the 3' UTR of ERAP1 A variant, but not the
      3' UTR of ERAP1 G variant, and, accordingly, ERAP1 expression is reduced both at
      RNA and protein levels only in human fibroblasts homozygous for the A variant.
      Consistently, HCMV-infected GG fibroblasts were more efficient in trimming viral
      antigens and being lysed by HCMV-peptide-specific CTLs. Notably, a significantly
      decreased HCMV seropositivity was detected among GG individuals suffering from
      multiple sclerosis, a disease model in which HCMV is negatively associated with
      adult-onset disorder. Overall, our results identify a resistance mechanism to
      HCMV miR-UL112-5p-based immune evasion strategy with potential implications for
      individual susceptibility to infection and other diseases.

PMID- 28746871
TI  - The Histone Methyltransferase Ezh2 Controls Mechanisms of Adaptive Resistance to
      Tumor Immunotherapy.
AB  - Immunotherapy and particularly immune checkpoint inhibitors have resulted in
      remarkable clinical responses in patients with immunogenic tumors, although most
      cancers develop resistance to immunotherapy. The molecular mechanisms of tumor
      resistance to immunotherapy remain poorly understood. We now show that induction
      of the histone methyltransferase Ezh2 controls several tumor cell-intrinsic and
      extrinsic resistance mechanisms. Notably, T cell infiltration selectively
      correlated with high EZH2-PRC2 complex activity in human skin cutaneous melanoma.
      During anti-CTLA-4 or IL-2 immunotherapy in mice, intratumoral tumor necrosis
      factor-alpha (TNF-alpha) production and T cell accumulation resulted in increased
      Ezh2 expression in melanoma cells, which in turn silenced their own
      immunogenicity and antigen presentation. Ezh2 inactivation reversed this
      resistance and synergized with anti-CTLA-4 and IL-2 immunotherapy to suppress
      melanoma growth. These anti-tumor effects depended on intratumorally accumulating
      interferon-gamma (IFN-gamma)-producing PD-1low CD8+ T cells and PD-L1
      downregulation on melanoma cells. Hence, Ezh2 serves as a molecular switch
      controlling melanoma escape during T cell-targeting immunotherapies.

PMID- 28746872
TI  - Aberrant Proteostasis of BMAL1 Underlies Circadian Abnormalities in a
      Paradigmatic mTOR-opathy.
AB  - Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder characterized
      by mutations in either the TSC1 or TSC2 genes, whose products form a critical
      inhibitor of the mechanistic target of rapamycin (mTOR). Loss of TSC1/2 gene
      function renders an mTOR-overactivated state. Clinically, TSC manifests with
      epilepsy, intellectual disability, autism, and sleep dysfunction. Here, we report
      that mouse models of TSC have abnormal circadian rhythms. We show that mTOR
      regulates the proteostasis of the core clock protein BMAL1, affecting its
      translation, degradation, and subcellular localization. This results in elevated
      levels of BMAL1 and a dysfunctional clock that displays abnormal timekeeping
      under constant conditions and exaggerated responses to phase resetting.
      Genetically lowering the dose of BMAL1 rescues circadian behavioral phenotypes in
      TSC mouse models. These findings indicate that BMAL1 deregulation is a feature of
      the mTOR-activated state and suggest a molecular mechanism for mitigating
      circadian phenotypes in a neurodevelopmental disorder.

PMID- 28746873
TI  - Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in
      Platelet and Megakaryocyte Function.
AB  - Anucleate platelets circulate in the blood to facilitate thrombosis and diverse
      immune functions. Platelet activation leading to clot formation correlates with
      increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid
      production. Simultaneous deletion of glucose transporter (GLUT) 1 and GLUT3
      (double knockout [DKO]) specifically in platelets completely abolished glucose
      uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic
      substrates, such as glutamate, increased. Thrombosis and platelet activation were
      decreased through impairment at multiple activation nodes, including Ca2+
      signaling, degranulation, and integrin activation. DKO mice developed
      thrombocytopenia, secondary to impaired pro-platelet formation from
      megakaryocytes, and increased platelet clearance resulting from cytosolic calcium
      overload and calpain activation. Systemic treatment with oligomycin, inhibiting
      mitochondrial metabolism, induced rapid clearance of platelets, with circulating
      counts dropping to zero in DKO mice, but not wild-type mice, demonstrating an
      essential role for energy metabolism in platelet viability. Thus, substrate
      metabolism is essential for platelet production, activation, and survival.

PMID- 28746874
TI  - Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress.
AB  - Glycolysis is upregulated under conditions such as hypoxia and high energy demand
      to promote cell proliferation, although the mechanism remains poorly understood.
      We find that hypoxia in Saccharomyces cerevisiae induces concentration of
      glycolytic enzymes, including the Pfk2p subunit of the rate-limiting
      phosphofructokinase, into a single, non-membrane-bound granule termed the
      "glycolytic body" or "G body." A yeast kinome screen identifies the yeast
      ortholog of AMP-activated protein kinase, Snf1p, as necessary for G-body
      formation. Many G-body components identified by proteomics are required for G
      body integrity. Cells incapable of forming G bodies in hypoxia display abnormal
      cell division and produce inviable daughter cells. Conversely, cells with G
      bodies show increased glucose consumption and decreased levels of glycolytic
      intermediates. Importantly, G bodies form in human hepatocarcinoma cells in
      hypoxia. Together, our results suggest that G body formation is a conserved,
      adaptive response to increase glycolytic output during hypoxia or tumorigenesis.

PMID- 28746875
TI  - Kmt5a Controls Hepatic Metabolic Pathways by Facilitating RNA Pol II Release from
      Promoter-Proximal Regions.
AB  - H4K20 monomethylation maintains genome integrity by regulating proper mitotic
      condensation, DNA damage response, and replication licensing. Here, we show that,
      in non-dividing hepatic cells, H4K20Me1 is specifically enriched in active gene
      bodies and dynamically regulated by the antagonistic action of Kmt5a methylase
      and Kdm7b demethylase. In liver-specific Kmt5a-deficient mice, reduced levels of
      H4K20Me1 correlated with reduced RNA Pol II release from promoter-proximal
      regions. Genes regulating glucose and fatty acid metabolism were most sensitive
      to impairment of RNA Pol II release. Downregulation of glycolytic genes resulted
      in an energy starvation condition partially compensated by AMP-activated protein
      kinase (AMPK) activation and increased mitochondrial activity. This metabolic
      reprogramming generated a highly sensitized state that, upon different metabolic
      stress conditions, quickly aggravated into a senescent phenotype due to ROS
      overproduction-mediated oxidative DNA damage. The results illustrate how defects
      in the general process of RNA Pol II transition into a productive elongation
      phase can trigger specific metabolic changes and genome instability.

PMID- 28746876
TI  - WBSCR16 Is a Guanine Nucleotide Exchange Factor Important for Mitochondrial
      Fusion.
AB  - Regulated inter-mitochondrial fusion/fission is essential for maintaining optimal
      mitochondrial respiration and control of apoptosis and autophagy. In mammals,
      mitochondrial fusion is controlled by outer membrane GTPases MFN1 and MFN2 and by
      inner membrane (IM) GTPase OPA1. Disordered mitochondrial fusion/fission
      contributes to various pathologies, and MFN2 or OPA1 mutations underlie
      neurodegenerative diseases. Here, we show that the WBSCR16 protein is primarily
      associated with the outer face of the inner mitochondrial membrane and is
      important for mitochondrial fusion. We provide evidence of a WBSCR16/OPA1
      physical interaction in the intact cell and of a WBSCR16 function as an OPA1
      specific guanine nucleotide exchange factor (GEF). Homozygosity for a Wbscr16
      mutation causes early embryonic lethality, whereas neurons of mice heterozygous
      for the mutation have mitochondria with reduced membrane potential and increased
      susceptibility to fragmentation upon exposure to stress, suggesting roles for
      WBSCR16 deficits in neuronal pathologies.

PMID- 28746877
TI  - Phospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation
      upon Amino Acid Starvation.
AB  - Most cellular stresses induce protein translation inhibition and stress granule
      formation. Here, using Drosophila S2 cells, we investigate the role of
      G3BP/Rasputin in this process. In contrast to arsenite treatment, where
      dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that,
      upon amino acid starvation, only the phosphorylated Ser142 form is recruited.
      Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit
      site, as a Rasputin interactor and stabilizer. Sec16 depletion results in
      Rasputin degradation and inhibition of stress granule formation. However, in the
      absence of Sec16, pharmacological stabilization of Rasputin is not enough to
      rescue the assembly of stress granules. This is because Sec16 specifically
      interacts with phosphorylated Ser142 Rasputin, the form required for stress
      granule formation upon amino acid starvation. Taken together, these results
      demonstrate that stress granule formation is fine-tuned by specific signaling
      cues that are unique to each stress. These results also expand the role of Sec16
      as a stress response protein.

PMID- 28746878
TI  - The Type VI Secretion System Engages a Redox-Regulated Dual-Functional Heme
      Transporter for Zinc Acquisition.
AB  - The type VI secretion system was recently reported to be involved in zinc
      acquisition, but the underlying mechanism remains unclear. Here, we report that
      Burkholderia thailandensis T6SS4 is involved in zinc acquisition via secretion of
      a zinc-scavenging protein, TseZ, that interacts with the outer membrane heme
      transporter HmuR. We find that HmuR is a redox-regulated dual-functional
      transporter that transports heme iron under normal conditions but zinc upon
      sensing extracellular oxidative stress, triggered by formation of an
      intramolecular disulfide bond. Acting as the first line of defense against
      oxidative stress, HmuR not only guarantees an immediate response to the changing
      environment but also provides a fine-tuned mechanism that allows a gradual
      response to perceived stress. The T6SS/HmuR-mediated active zinc transport system
      is also involved in bacterial virulence and contact-independent bacterial
      competition. We describe a sophisticated bacterial zinc acquisition mechanism
      affording insights into the role of metal ion transport systems.

PMID- 28746879
TI  - Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and
      Contributes to Hydrocephalus.
AB  - Motile cilia in ependymal cells, which line the cerebral ventricles, exhibit a
      coordinated beating motion that drives directional cerebrospinal fluid (CSF) flow
      and guides neuroblast migration. At the apical cortex of these multi-ciliated
      cells, asymmetric localization of planar cell polarity (PCP) proteins is required
      for the planar polarization of microtubule dynamics, which coordinates cilia
      orientation. Daple is a disheveled-associating protein that controls the non
      canonical Wnt signaling pathway and cell motility. Here, we show that Daple
      deficient mice present hydrocephalus and their ependymal cilia lack coordinated
      orientation. Daple regulates microtubule dynamics at the anterior side of
      ependymal cells, which in turn orients the cilial basal bodies required for the
      directional cerebrospinal fluid flow. These results demonstrate an important role
      for Daple in planar polarity in motile cilia and provide a framework for
      understanding the mechanisms and functions of planar polarization in the
      ependymal cells.

PMID- 28746880
TI  - TGF-beta Signaling Is Necessary and Sufficient for Pharyngeal Arch Artery
      Angioblast Formation.
AB  - The pharyngeal arch arteries (PAAs) are transient embryonic blood vessels that
      mature into critical segments of the aortic arch and its branches. Although
      defects in PAA development cause life-threating congenital cardiovascular
      defects, the molecular mechanisms that orchestrate PAA morphogenesis remain
      unclear. Through small-molecule screening in zebrafish, we identified TGF-beta
      signaling as indispensable for PAA development. Specifically, chemical inhibition
      of the TGF-beta type I receptor ALK5 impairs PAA development because nkx2.5+ PAA
      progenitor cells fail to differentiate into tie1+ angioblasts. Consistent with
      this observation, we documented a burst of ALK5-mediated Smad3 phosphorylation
      within PAA progenitors that foreshadows angioblast emergence. Remarkably,
      premature induction of TGF-beta receptor activity stimulates precocious
      angioblast differentiation, thereby demonstrating the sufficiency of this pathway
      for initiating the PAA progenitor to angioblast transition. More broadly, these
      data uncover TGF-beta as a rare signaling pathway that is necessary and
      sufficient for angioblast lineage commitment.

PMID- 28746881
TI  - Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4+
      T Cells.
AB  - To characterize susceptibility to HIV infection, we phenotyped infected tonsillar
      T cells by single-cell mass cytometry and created comprehensive maps to identify
      which subsets of CD4+ T cells support HIV fusion and productive infection. By
      comparing HIV-fused and HIV-infected cells through dimensionality reduction,
      clustering, and statistical approaches to account for viral perturbations, we
      identified a subset of memory CD4+ T cells that support HIV entry but not viral
      gene expression. These cells express high levels of CD127, the IL-7 receptor, and
      are believed to be long-lived lymphocytes. In HIV-infected patients, CD127
      expressing cells preferentially localize to extrafollicular lymphoid regions with
      limited viral replication. Thus, CyTOF-based phenotyping, combined with
      analytical approaches to distinguish between selective infection and receptor
      modulation by viruses, can be used as a discovery tool.

PMID- 28746883
TI  - Comparing undergraduate and community-recruited adult non-gamblers' motives for
      not gambling: Do they differ?
AB  - The field of gambling studies has extensively focused on isolating risk factors
      for developing a gambling disorder. Conversely, little attention has been paid to
      identifying protective factors against gambling disorder among people who choose
      to not gamble at all. Moreover, the limited number of studies that have focused
      on non-gamblers have neglected to differentiate current from lifetime non
      gamblers. The purpose of the present study was to examine motives for not
      gambling among a diverse sample of adult lifetime non-gamblers recruited from the
      community and to compare these motives to an undergraduate student sample of non
      gamblers from a previous study. Participants consisted of 219 lifetime non
      gamblers (45.2% male) from the United States recruited via Amazon's Mechanical
      Turk. The previously recruited sample consisted of Canadian undergraduate
      students (n=196). Eight distinct categories of motivations for not gambling were
      identified in the sample of adult community non-gamblers, which corresponded
      closely with previous findings from the student sample. However, comparisons
      between the two samples revealed that adult lifetime non-gamblers were more
      likely to provide financial motives as reasons for not gambling. Whereas, the
      student sample was more likely to mention disinterest and the influence of others
      as reasons to avoid gambling. Results suggest that the choice not to gamble among
      lifetime non-gamblers may reflect a more conscious, values-based decision when
      compared to undergraduate non-gamblers.

PMID- 28746882
TI  - A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals
      Principles for Controlling Tumor Evolution.
AB  - Combinatorial inhibition of effector and feedback pathways is a promising
      treatment strategy for KRAS mutant cancers. However, the particular pathways that
      should be targeted to optimize therapeutic responses are unclear. Using
      CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates
      with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70
      screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers,
      we uncovered universal and tissue-specific sensitizing combinations involving
      inhibitors of cell cycle, metabolism, growth signaling, chromatin regulation, and
      transcription. Furthermore, these screens revealed secondary genetic modifiers of
      sensitivity, yielding a SRC inhibitor-based combination therapy for KRAS/PIK3CA
      double-mutant colorectal cancers (CRCs) with clinical potential. Surprisingly,
      acquired resistance to combinations of growth signaling pathway inhibitors
      develops rapidly following treatment, but by targeting signaling feedback or
      apoptotic priming, it is possible to construct three-drug combinations that
      greatly delay its emergence.

PMID- 28746884
TI  - Effects of single and combined use of bacteriophages and antibiotics to
      inactivate Escherichia coli.
AB  - A major concern of phage therapy is the emergency of phage-resistant mutants.
      This limitation can be overcome by the combined use of phages and antibiotics. It
      has been shown that the combination of antibiotics and phages is an alternative
      that cannot only be effective at reducing bacterial numbers, but also to
      contribute to the management of resistance levels. However, this view has only
      been discussed with regard to antibiotic resistance and not to control phage
      mutant emergence. In our study we compared not only the resistance of the
      bacteria to the four antibiotics tested with and without phages addition, but
      also the resistance to the phages in the presence and absence of antibiotics. The
      aim of this study was to evaluate the potential synergistic effect of phages and
      antibiotics in the inactivation of Escherichia coli in order to control
      infections, namely urinary tract infection (UTI), and to reduce the development
      of bacterial resistance to phages. Phage therapy combined with antibiotics
      (ampicillin, piperacillin, kamanycin, tetracycline, chloramphenicol and
      ciprofloxacin) was evaluated in the inactivation of E. coli, both in saline
      solution and urine samples. Phage and antibiotic combinations could result in
      high synergistic effects in the inactivation of bacteria. The combination of
      phage and ciprofloxacin at sublethal concentration decreased the bacterial counts
      in urine samples by 7.8+/-0.1 log CFU/ml after 8h, but when phages or the
      antibiotic were tested alone, the decrease was of 3.9+/-0.3 log CFU/mL and 1.2+/
      0.1 log CFU/mL, respectively, after the same time. The efficacy of the
      combination of the two therapies depends on the antibiotic resistance status of
      the targeted bacteria to the employed antibiotic and of the antibiotic type
      (bactericide or bacteriostatic), causing the same or less bacterial resistance
      than phages and antibiotics applied alone (1.2+/-1.0*10-5 to 2.4+/-1.5*10-7
      CFU/mL for the combined treatment, 2.7+/-0.2*10-4 CFU/mL for the antibiotics and
      5.0+/-1.5*10-6 CFU/mL for the phages). The addition of antibiotics, at
      subinhibitory concentration, during phage treatment can control the phage-mutant.
      The high bacterial inactivation efficiency of these combined techniques and the
      long periods of phage survival in urine, pave the way for depth studies to
      control UTI and to overcome the development of resistances by bacteria.

PMID- 28746885
TI  - Injectable hydrogel based on quaternized chitosan, gelatin and dopamine as
      localized drug delivery system to treat Parkinson's disease.
AB  - There is still an enormous demand for designing materials to the treatment of
      Parkinson's disease, and dopamine-based injectable polysaccharide hydrogels as
      localized drug delivery system have huge potential. Here, we developed a facile
      approach to prepare dopamine-based and polydopamine crosslinked injectable
      hydrogels by simply oxidizing a mixture of quaternized chitosan, gelatin and
      dopamine under physiological conditions. These injectable hydrogels showed stable
      mechanical strength by rheometer and exhibited good degradability evaluated by in
      vitro degradation test. The chemical structure and morphology of the hydrogels
      were characterized by FT-IR and SEM. Dopamine as a drug for treating Parkinson's
      disease and metronidazole as an anti-inflammatory drug were encapsulated in the
      hydrogel. The release profiles indicated that the injectable hydrogels have great
      capacity as a carrier for long-term localized release system for dopamine and
      metronidazole. Furthermore, the cytocompatibility of the hydrogels was confirmed
      by cell viability and proliferation assays using mouse L929 fibroblast cells.
      This work provides a new and facile approach to prepare dopamine-based injectable
      materials which can be used as long-term injectable sustained release system for
      dopamine as well as anti-inflammatory drug for Parkinson's treatment.

PMID- 28746886
TI  - In vitro enzymatic hydrolysis of amylopectins from rice starches.
AB  - The effects of the molecular structures of amylopectins on the enzymatic
      hydrolysis of waxy-rice amylopectin (WRA) and normal-rice amylopectin (NRA) were
      investigated. The results indicated that compared to NRA, WRA possessed larger
      chain length, number of chains, internal chain length, degree of polymerisation,
      interblock chain length, and lower degree of branching and short:long B-chains,
      which caused WRA was much less susceptible to enzymatic hydrolysis than NRA. The
      digestibility curves for WRA and NRA were well fitted by the first-order kinetic
      equation. WRA and NRA were hydrolyzed in two separates phases in the LOS plots.
      Whether using alpha-amylase alone, or together with amyloglucosidase, WRA and NRA
      exhibited different digestibility rates due to different chain structure of
      amylopectin. The low C1infinity values predicted that WRA and NRA would have
      little impact on blood glucose concentrations in the early digestion stage. HPLC
      results showed that G1~G5 from WRA using alpha-amylase were lower than that from
      NRA, whereas from WRA were higher than that from NRA. There was the synergism
      between alpha-amylase and amyloglucosidase in glucose released from WRA and NRA.

PMID- 28746887
TI  - Optimization of carboxymethyl cellulose hydrogels beads generated by an anionic
      surfactant micelle templating for cationic dye uptake: Swelling, sorption and
      reusability studies.
AB  - Carboxymethyl cellulose hydrogels beads were synthesized by ionotropic gelation
      in Al3+ solutions with or without sodium n-dodecyl sulfate (SDS) surfactant as a
      pore-forming micelle templating and NaCl as porogen agent. FTIR spectroscopy and
      EDX analysis evidenced the formation of hydrogels. The morphology observed by
      Scanning Electron Microscopy (SEM) showed rough porous surfaces. The swelling
      properties in various media were studied. The addition of SDS optimized the
      capacity and initial rate of swelling. The porous beads were assessed as
      adsorbents to remove methylene blue (MB) dye from aqueous solutions by varying
      parameters: pH medium, adsorbent dose, initial MB concentration, and contact
      time. The kinetics obeyed well to pseudo-second-order model and the isotherms
      data followed Langmuir model with a maximum of adsorption capacity of 82mgg-1.
      Thermodynamic studies showed spontaneous and endothermic nature of the process.
      From reusability study, all beads are well regenerated and displayed unexpected
      increase in removal efficiency compared to starting ones, with an optimal
      capacity of 350mgg-1. This fact is due to dye entrapped in the desorbed beads
      that favored subsequent dye access to internal sites. In view of effectiveness of
      adsorption and regeneration, the optimized hydrogels are promising as low cost
      dyes adsorbents.

PMID- 28746888
TI  - Curcumin-loaded chitosan/carboxymethyl starch/montmorillonite bio-nanocomposite
      for reduction of dental bacterial biofilm formation.
AB  - A novel bio nanocomposite of Carboxymethyl Starch (CMS)-Chitosan (CS)
      Montmorillonite (MMT) was developed for Curcumin delivery. To improve Curcumin
      entrapment into Cs-CMS-MMT, different ratios of Chitosan (Cs), Carboxymethyl
      Starch (CMS) and MMT were used. Particle size and Curcumin entrapment efficiency
      (EE) were highly affected by different formulation variables. Polysaccharide
      concentration, Cs-CMS ratio and sonication time had significant effect on
      particle size. MMT addition enhanced the entrapment efficiency. To optimize
      entrapment efficiency of Curcumin, statistical analysis was used, and an
      experiment based on screening design performed with two variants. Morphology and
      structural characterization of nanocomposite and Curcumin entrapment efficiency
      were analyzed. The optimal formulation had the average particles size of 35.9nm
      with Curcumin entrapment efficiency of 91%. Finally, the antibacterial activity
      of bio nanocomposite against Streptococcus mutans was assessed. Curcumin-loaded
      bio nanocomposite hindered the formation of biofilm on dental models very
      effectively.

PMID- 28746889
TI  - Molecular recognition between potential natural inhibitors of the Keap1-Nrf2
      complex.
AB  - Disrupting the Keap1-Nrf2 pathway enhances Nrf2 activity, which has been
      identified as an important approach for the prevention of different chronic
      diseases in which oxidative stress and inflammation are present, such as cancer,
      diabetes, Alzheimer's and Parkinson's. Based on the high potential to modulate
      antioxidant, anti-inflammatory and anticancer properties that the discovery of
      Keap1-Nrf2 protein-protein interaction inhibitors would represent, the
      utilization of some natural compounds has emerged as a promising strategy to
      identify new drugs. To gain insight into the structural and energetic basis of
      the molecular recognition between some natural inhibitors that could work as
      inhibitors of the Keap1-Nrf2 complex, we evaluated the binding properties between
      four natural compounds present in the extract of Geranium schiedeanum (Gs): 3-O-a
      L arabinofuranoside-7-O-a-l-rhamnopyranoside of kaempferol (KAM), gallic acid
      (GAL), ellagic acid (ELL) and geranium acetonitrile (ACE), which based on
      experimental findings have been proposed as possible Keap1-Nrf2 PPI inhibitors.
      Computational studies combining docking and MD simulations accompanied by the
      MMGBSA approach revealed that KAM and ACE directly interact with residues in the
      Kelch domain that participate in the molecular recognition of Nrf2, indicating
      that both natural compounds could act as activators of Nrf2, whereas GAL and ELL
      are possible free radical scavengers.

PMID- 28746890
TI  - Aged-engineered nanoparticles effect on sludge anaerobic digestion performance
      and associated microbial communities.
AB  - To investigate the potential effect of aged engineered nanoparticles (a-ENPs) on
      sludge digestion performance, 150L pilot anaerobic digesters (AD) were fed with a
      blend of primary and waste activated sludge spiked either with a mixture of
      silver oxide, titanium dioxide and zinc oxide or a mixture of their equivalent
      bulk metal salts to achieve a target concentration of 250, 2000, and 2800mgkg-1
      dry weight, respectively. Volatile fatty acids (VFA) were 1.2 times higher in the
      spiked digesters and significantly different (p=0.05) from the control
      conditions. Specifically, isovaleric acid concentration was 2 times lower in the
      control digester compared to the spiked digesters, whereas hydrogen sulfide was 2
      times lower in the ENPs spiked digester indicating inhibitory effect on sulfate
      reducing microorganisms. Based on the ether-linked isoprenoids concentration, the
      total abundance of methanogens was 1.4 times lower in the ENPs spiked digester
      than in the control and metal salt spiked digesters. Pyrosequencing indicated 80%
      decrease in abundance and diversity of methanogens in ENPs spiked digester
      compared to the control digester. Methanosarcina acetivorans and Methanosarcina
      barkeri were identified as nano-tolerant as their relative abundance increased by
      a factor of 6 and 11, respectively, compared to the other digesters. The results
      further provide compelling evidence on the resilience of Fusobacteria,
      Actinobacteria and the Trojan horse-like effect of ENPs which offered a
      competitive advantage to some organisms while reducing microbial abundance and
      diversity.

PMID- 28746891
TI  - Long-term variations in sediment heavy metals of a reservoir with changing
      trophic states: Implications for the impact of climate change.
AB  - Two dated sediment cores from the Miyun Reservoir of Beijing in China were
      analyzed to reconstruct the pollution history of heavy metals including cadmium
      (Cd), chromium (Cr), iron (Fe), nickel (Ni), and zinc (Zn) as well as phosphorus
      (P). Enrichment factor (EF) and geoaccumulation index (Igeo) were applied to
      assess the enrichment status of heavy metals. Average EF and Igeo values
      indicated that the studied heavy metals in the sediments mainly originated from
      non-point source pollution and soil-water erosion, showing low ecological risks.
      In addition, correlation analysis and principal component analysis (PCA)
      identified that Cd, Zn, and P were mainly from agricultural diffusion pollution
      caused by utilization of the phosphate fertilizer; Zn, Ni, and Cr originated from
      soil erosion. PCA analysis was further conducted to investigate the relationships
      among meteorological factors, algae-dominant total organic carbon (TOC), and
      heavy metals. Results showed that algae-dominant TOC had strong positive
      correlation with temperature, which can be explained by that increased
      temperature accelerated the growth of algae. Meanwhile the opposite loadings
      between algae-dominant TOC and heavy metal suggested that primary production
      played an important role in migration and transformation of metals. Moreover,
      stepwise multiple regression models showed that Fe was sensitive to temperature,
      which accounted for approximately 39.0% and 40.1% of the variations in Fe of two
      sediment cores, respectively. Fe showed significant decreasing trends during the
      past 50years. Reductive environment of water-sediment interface caused by
      increasing temperature probably contributed to the restoration of ferric iron,
      resulting in the release of soluble Fe to overlying waters. Future climate change
      with elevated temperature and extreme weather events will aggravate the
      ecological risk of heavy metals in water environment due to the enhanced leaching
      effect and non-point source pollution as well as the release of heavy metals from
      sediments to water environment.

PMID- 28746892
TI  - The impact of two large floods (1993-1994) on sediment deposition in the Rhone
      delta: Implications for sustainable management.
AB  - In October 1993 and January 1994, two large floods with peak discharge of 9800
      and 10,980m3/s and total suspended solid transport of 10.7*106 and 9.7*106 tons,
      respectively, occurred on the Rhone River. Both floods led to multiple levee
      breeches in the Northern part of the delta resulting in the introduction of
      131*106 and 54.9*106m3 of river water, respectively. In both cases, the flood
      water drained to the southern lagoons and was partly pumped directly back to the
      Rhone or to the sea. Most of the 390,000 tons of sediment introduced remained in
      the Northern inundated area with accretion ranging from 70mm near the breaches to
      4mm 6-8km away. This last value is close to the mean accretion value (3.7mm)
      inferred from the water budget and the estimation of the total quantity of
      sediment introduced in the flooded area. In a small area near the mouth of the
      Rhone river still receiving natural overflow from the river, total deposition
      during both floods was as high as 10cm. The Rhone delta is facing an uncertain
      future with projected sea-level rise. The results of this study show that large
      introductions of river water can help sustain the delta in the face of climate
      change. Controlled introductions of river water using riverside closable
      structures, as in being done in other deltas, could be done in a way that
      delivers water and sediments to the places where it is needed most and at the
      same time protect important infrastructure.

PMID- 28746893
TI  - In vitro vascular toxicity of tariquidar, a potential tool for in vivo PET
      studies.
AB  - The P-glicoprotein (P-gp) inhibitor tariquidar is used to detect functional
      alterations of blood brain barrier pumps in PET imaging. The doses required,
      however, up to 4-fold higher than those already used in clinical trials to
      reverse multidrug resistance, cause syncopal episode and hypotension. Therefore,
      the effects of these doses toward the vasculature were investigated and an in
      depth analysis of tariquidar-mediated effects on A7r5 and EA.hy926 cells
      viability, on the mechanical activity of freshly and cultured rat aorta rings and
      on L-type Ca2+ current [ICa(L)] of A7r5 cells has been performed. In both A7r5
      and EA.hy926 cells, tariquidar was not cytotoxic up to 1MUM concentration. On the
      contrary, at 10MUM, it caused apoptosis already after 24h treatment. In fresh
      aorta rings, 10MUM tariquidar partially relaxed phenylephrine-, but not 60mM K+
      (K60)-induced contraction. In rings treated with 10MUM tariquidar for 7days, the
      contractile response to both phenylephrine and K60 remained unchanged. Finally,
      tariquidar did not modify ICa1.2 intensity and kinetics. In conclusion,
      Tariquidar might exert both cytotoxic and acute, weak vascular effects at
      concentrations comparable to those employed in PET imaging. This implies that
      caution should be exercised when using it as diagnostic tool.

PMID- 28746894
TI  - SAMPA: A free software tool for skin and membrane permeation data analysis.
AB  - Skin and membrane permeation experiments comprise an important step in the
      development of a transdermal or topical formulation or toxicological risk
      assessment. The standard method for analyzing these data relies on the linear
      part of a permeation profile. However, it is difficult to objectively determine
      when the profile becomes linear, or the experiment duration may be insufficient
      to reach a maximum or steady state. Here, we present a software tool for Skin And
      Membrane Permeation data Analysis, SAMPA, that is easy to use and overcomes
      several of these difficulties. The SAMPA method and software have been validated
      on in vitro and in vivo permeation data on human, pig and rat skin and model
      stratum corneum lipid membranes using compounds that range from highly lipophilic
      polycyclic aromatic hydrocarbons to highly hydrophilic antiviral drug, with and
      without two permeation enhancers. The SAMPA performance was compared with the
      standard method using a linear part of the permeation profile and a complex
      mathematical model. SAMPA is a user-friendly, open-source software tool for
      analyzing the data obtained from skin and membrane permeation experiments. It
      runs on a Microsoft Windows platform and is freely available as a Supporting file
      to this article.

PMID- 28746895
TI  - Effects on human bronchial epithelial cells following low-dose chronic exposure
      to nanomaterials: A 6-month transformation study.
AB  - The most plausible exposure route to manufactured nanomaterials (MNM) remains
      pulmonary inhalation. Yet, few studies have attempted to assess carcinogenic
      properties in vitro following long-term exposure of human pulmonary cells to low
      and occupationally relevant doses. The most advanced in vitro tests for
      carcinogenicity, the cell transformation assay (CTA), rely mostly on rodent cells
      and short-term exposure. We hypothesized that long-term exposure of human
      bronchial epithelial cells with a normal phenotype could be a valuable assay for
      testing carcinogenicity of nanomaterials. Therefore, this study (performed within
      the framework of the FP7-NANoREG project) assessed carcinogenic potential of
      chronic exposure (up to 6months) to low doses of multi-walled carbon nanotubes
      (MWCNT, NM-400 and NM-401) and TiO2 materials (NM62002 and KC7000). In order to
      harmonize and standardize the experiments, standard operating protocols of MNM
      dispersion (NANOGENOTOX) were used by three different NANoREG project partners.
      All nanomaterials showed low cytotoxicity in short-term tests for the tested
      doses (0.96 and 1.92MUg/cm2). During long-term exposure, however, NM-401 clearly
      affected cell proliferation. In contrast, no cell transformation was observed for
      NM-401 by any of the partners. NM-400 and NM62002 formed some colonies after
      3months. We conclude that agglomerated NM-401 in low doses affect cell
      proliferation but do not cause cell transformation in the CTA assay used.

PMID- 28746896
TI  - Prenatal developmental toxicity testing of petroleum substances: Application of
      the mouse embryonic stem cell test (EST) to compare in vitro potencies with
      potencies observed in vivo.
AB  - Prenatal developmental toxicity (PDT) as observed with some petroleum substances
      (PS) has been associated with the presence of 3-7 ring polycyclic aromatic
      hydrocarbons (PAHs). In the present study, the applicability of ES-D3 cell
      differentiation assay of the EST to evaluate in vitro embryotoxicity potencies of
      PS and gas-to-liquid (GTL) products as compared to their in vivo potencies was
      investigated. DMSO-extracts of a range of PS, containing different amounts of
      PAHs, and GTL-products, which are devoid of PAHs, were tested in the ES-D3 cell
      proliferation and differentiation assays of the EST. The results show that PS
      inhibited the differentiation of ES-D3 cells into cardiomyocytes in a
      concentration-dependent manner at non-cytotoxic concentrations, and that their
      potency was proportional to their PAH content. In contrast, as expected, GTL
      products did not inhibit ES-D3 cell viability or differentiation at all. The in
      vitro PDT potencies were compared to published in vivo PDT studies, and a good
      correlation was found between in vitro and in vivo results (R2=0.97). To
      conclude, our results support the hypothesis that PAHs are the primary inducers
      of the PDT in PS.

PMID- 28746897
TI  - Parkinsonian features in aging GFAP.HMOX1 transgenic mice overexpressing human HO
      1 in the astroglial compartment.
AB  - Epigenetic influences mediating brain iron deposition, oxidative mitochondrial
      injury, and macroautophagy in Parkinson disease and related conditions remain
      enigmatic. Here, we show that selective overexpression of the stress protein,
      heme oxygenase-1 (HO-1) in astrocytes of GFAP.HMOX1 transgenic mice between 8.5
      and 19 months of age results in nigrostriatal hypodopaminergia associated with
      locomotor incoordination and stereotypy; downregulation of tyrosine hydroxylase,
      DAT, LMX1B, Nurr1, Pitx3 and DJ-1 mRNA and/or protein; overproduction of alpha
      synuclein and ubiquitin; oxidative stress; basal ganglia siderosis; mitochondrial
      damage/mitophagy; and augmented GABAergic systems (increased GABA, GAD67 and
      reelin). The neurophenotype of these GFAP.HMOX18.5-19m mice is highly consistent
      with parkinsonism and differs dramatically from the schizophrenia-like features
      previously documented in younger GFAP.HMOX10-12m mice. Common stressors may
      elicit either early-onset developmental (schizophrenia) or later-life
      degenerative (PD) brain disorders depending on whether the glial HO-1 response is
      engaged prior to or following the maturation of dopaminergic circuitry.
      Curtailment of glial HO-1 transduction at strategic points of the life course may
      confer neuroprotection in human degenerative and developmental central nervous
      system disorders.

PMID- 28746898
TI  - Circulating levels of the angiogenesis mediators endoglin, HB-EGF, BMP-9 and FGF
      2 in patients with severe sepsis and septic shock.
AB  - PURPOSE: Endothelial barrier dysfunction is a hallmark of sepsis, and is at least
      partially mediated by pathways that regulate endothelial barrier assembly during
      angiogenesis. Not surprisingly, increased levels of key angiogenic proteins such
      as VEGF-A and Angiopoietin-2 have been described in sepsis. The purpose of this
      study was to investigate if additional pathways that regulate endothelial barrier
      integrity during angiogenesis could also be involved in the host response of
      sepsis. MATERIAL AND METHODS: We evaluated circulating levels of four proteins
      involved in angiogenesis, not previously studied in sepsis, in a cohort of 50
      patients with severe sepsis and septic shock. RESULTS: Circulating levels of BMP
      9 and FGF-2 were similar in patients and healthy volunteers. In contrast,
      patients with septic shock presented 1.5-fold higher levels of endoglin
      (P=0.004), and 2-fold lower levels of Heparin-Binding EGF-like growth factor (HB
      EGF) (P=0.002) when compared to healthy individuals. Of note, HB-EGF deficiency
      has been recently demonstrated to be detrimental to survival in a murine model of
      sepsis. CONCLUSIONS: Endoglin and HB-EGF could be involved in the host response
      of sepsis. Additional studies are warrant to investigate their role as biomarker
      or therapeutic targets in sepsis.

PMID- 28746899
TI  - Hypertonic saline in critical illness - A systematic review.
AB  - INTRODUCTION: The optimal approach to fluid management in critically ill patients
      is highly debated. Fluid resuscitation using hypertonic saline was used in the
      past for more than thirty years, but has recently disappeared from clinical
      practice. Here we provide an overview on the currently available literature on
      effects of hypertonic saline infusion for fluid resuscitation in the critically
      ill. METHODS: Systematic analysis of reports of clinical trials comparing effects
      of hypertonic saline as resuscitation fluid to other available crystalloid
      solutions. A literature search of MEDLINE and the Cochrane Controlled Clinical
      trials register (CENTRAL) was conducted to identify suitable studies. RESULTS:
      The applied search strategy produced 2284 potential publications. After
      eliminating doubles, 855 titles and abstracts were screened and 40 references
      retrieved for full text analysis. At total of 25 scientific studies meet the
      prespecified inclusion criteria for this study. CONCLUSION: Fluid resuscitation
      using hypertonic saline results in volume expansion and less total infusion
      volume. This may be of interest in oedematous patients with intravascular volume
      depletion. When such strategies are employed, renal effects may differ markedly
      according to prior intravascular volume status. Hypertonic saline induced changes
      in serum osmolality and electrolytes return to baseline within a limited period
      in time. Sparse evidence indicates that resuscitation with hypertonic saline
      results in less perioperative complications, ICU days and mortality in selected
      patients. In conclusion, the use of hypertonic saline may have beneficial
      features in selected critically ill patients when carefully chosen. Further
      clinical studies assessing relevant clinical outcomes are warranted.

PMID- 28746900
TI  - In-vivo electrochemical monitoring of H2O2 production induced by root-inoculated
      endophytic bacteria in Agave tequilana leaves.
AB  - A dual-function platinum disc microelectrode sensor was used for in-situ
      monitoring of H2O2 produced in A. tequilana leaves after inoculation of their
      endophytic bacteria (Enterobacter cloacae). Voltammetric experiments were carried
      out from 0.0 to -1.0V, a potential range where H2O2 is electrochemically reduced.
      A needle was used to create a small cavity in the upper epidermis of A. tequilana
      leaves, where the fabricated electrochemical sensor was inserted by using a
      manual three-dimensional micropositioner. Control experiments were performed with
      untreated plants and the obtained electrochemical results clearly proved the
      formation of H2O2 in the leaves of plants 3h after the E. cloacae inoculation,
      according to a mechanism involving endogenous signaling pathways. In order to
      compare the sensitivity of the microelectrode sensor, the presence of H2O2 was
      detected in the root hairs by 3,3-diaminobenzidine (DAB) stain 72h after
      bacterial inoculation. In-situ pH measurements were also carried out with a gold
      disc microelectrode modified with a film of iridium oxide and lower pH values
      were found in A. tequilana leaves treated with bacteria, which may indicate the
      plant produces acidic substances by biosynthesis of secondary metabolites. This
      microsensor could be an advantageous tool for further studies on the
      understanding of the mechanism of H2O2 production during the plant-endophyte
      interaction.

PMID- 28746901
TI  - Enhanced electrocatalytic activity of graphene-gold nanoparticles hybrids for
      peroxynitrite electrochemical detection on hemin-based electrode.
AB  - A simple, ultrasensitive peroxynitrite anion (ONOO-) electrochemical sensing
      platform was developed by immobilizing hemin on a density controllable
      electrochemically reduced graphene oxide-Au nanoparticles (ERGO-AuNPs)
      nanohybrids. The ERGO-AuNPs in situ nanohybrids were produced onto a glass carbon
      electrode (GCE) by one-step electrodeposition, the density of which could be
      easily controlled by electrodeposited time. The morphology of ERGO-AuNPs
      nanohybrids was characterized by a scanning electron microscope (SEM). The ERGO
      AuNPs nanohybrids showed a high electrocatalytic activity for immobilized-hemin,
      because the nanostructures hybrids could effectively promote electron transfer
      rate between hemin and the electrode. Due to nanohybrids-enhanced catalytic
      effect for hemin, they were firstly selected for use as a highly sensitive
      electrochemical platform for ONOO- detection. The resulted sensor showed a high
      electrocatalytic activity toward ONOO- oxidation, being free from the
      electroactive interferents, including nitrite, nitrate, dopamine and uric acid at
      an applied potential of 0.7V. The sensor exhibited a high sensitivity of
      123.1nAMUM-1 and a lower detection limit of 0.1MUM, and a wide linear range of
      2.4*10-6 to 5.5*10-5M, which could be attributed to the synergy between ERGO and
      AuNPs in hybrids. The nanohybrids in situ preparation and ONOO- detection methods
      would be beneficial to developing other sensing interface and have promising
      applications in biological molecules analysis and clinical diagnostic.

PMID- 28746902
TI  - Remembering verbally-presented items as pictures: Brain activity underlying
      visual mental images in schizophrenia patients with visual hallucinations.
AB  - BACKGROUND: Previous research suggests that visual hallucinations in
      schizophrenia consist of mental images mistaken for percepts due to failure of
      the reality-monitoring processes. However, the neural substrates that underpin
      such dysfunction are currently unknown. We conducted a brain imaging study to
      investigate the role of visual mental imagery in visual hallucinations. METHOD:
      Twenty-three patients with schizophrenia and 26 healthy participants were
      administered a reality-monitoring task whilst undergoing an fMRI protocol. At the
      encoding phase, a mixture of pictures of common items and labels designating
      common items were presented. On the memory test, participants were requested to
      remember whether a picture of the item had been presented or merely its label.
      RESULTS: Visual hallucination scores were associated with a liberal response bias
      reflecting propensity to erroneously remember pictures of the items that had in
      fact been presented as words. At encoding, patients with visual hallucinations
      differentially activated the right fusiform gyrus when processing the words they
      later remembered as pictures, which suggests the formation of visual mental
      images. On the memory test, the whole patient group activated the anterior
      cingulate and medial superior frontal gyrus when falsely remembering pictures.
      However, no differential activation was observed in patients with visual
      hallucinations, whereas in the healthy sample, the production of visual mental
      images at encoding led to greater activation of a fronto-parietal decisional
      network on the memory test. CONCLUSIONS: Visual hallucinations are associated
      with enhanced visual imagery and possibly with a failure of the reality
      monitoring processes that enable discrimination between imagined and perceived
      events.

PMID- 28746903
TI  - Outcomes of an online pharmacist-managed anticoagulation clinic for individuals
      on warfarin therapy living in rural communities.

PMID- 28746904
TI  - Prophylactic antidepressant treatment following acute coronary syndrome: A
      systematic review of randomized controlled trials.
AB  - Major depressive disorder is significantly increased in patients following acute
      coronary syndrome resulting in twofold increased mortality compared with patients
      without depression. The depression diagnosis is often missed leading to
      considerable undertreatment. This systematic review assesses the current evidence
      of primary prophylactic treatment of depression in patients after acute coronary
      syndrome. The study protocol was prospectively registered at PROSPERO
      (registration number CRD42015025587). A systematic review were conducted and
      reported according to Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines. PubMed, Embase, PsychINFO, CINAHL, and Cochran
      Library was searched. Two independent reviewers screened the records. The
      inclusion criteria were randomized controlled trials on adult patients with acute
      coronary syndrome treated prophylactically with an antidepressant intervention of
      any kind. A validated assessment tool should measure depression and depressive
      symptoms. Languages were limited to articles written in English. Six articles
      were included. Four studies utilized different components of case and disease
      management, health coaching, or relaxational audiotapes as intervention compared
      with usual care or with no formal program of rehabilitation. None of the studies
      showed any significant prophylactic effect against depression. One study with a
      program of health education and counselling and another study with a
      pharmacological antidepressant showed significant prophylactic effect on
      depression and depressive symptoms. All six included studies were associated with
      high risk of bias. There is not strong evidence of the effects of any type of
      routine antidepressant prophylaxis in patients following acute coronary syndrome.
      Further high quality studies are warranted.

PMID- 28746905
TI  - A PM7 dynamic residue-ligand interactions energy landscape of the BACE1
      inhibitory pathway by hydroxyethylamine compounds. Part I: The flap closure
      process.
AB  - BACE1 is an enzyme of scientific interest because it participates in the
      progression of Alzheimer's disease. Hydroxyethylamines (HEAs) are a family of
      compounds which exhibit inhibitory activity toward BACE1 at a nanomolar level,
      favorable pharmacokinetic properties and oral bioavailability. The first step in
      the inhibition of BACE1 by HEAs consists of their entrance into the protease
      active site and the resultant conformational change in the protein, from Apo to
      closed form. These two conformations differ in the position of an antiparallel
      loop (called the flap) which covers the entrance to the catalytic site. For
      BACE1, closure of this flap is vital to its catalytic activity and to inhibition
      of the enzyme due to the new interactions thereby formed with the ligand. In the
      present study a dynamic energy landscape of residue-ligand interaction energies
      (ReLIE) measured for 112 amino acids in the BACE1 active site and its immediate
      vicinity during the closure of the flap induced by 8 HEAs of different inhibitory
      power is presented. A total of 6.272 million ReLIE calculations, based on the PM7
      semiempirical method, provided a deep and quantitative view of the first step in
      the inhibition of the aspartyl protease. The information suggests that residues
      Asp93, Asp289, Thr292, Thr293, Asn294 and Arg296 are anchor points for the
      ligand, accounting for approximately 45% of the total protein-ligand interaction.
      Additionally, flap closure improved the BACE1-HEA interaction by around 25%.
      Furthermore, the inhibitory activity of HEAs could be related to the capacity of
      these ligands to form said anchor point interactions and maintain them over time:
      the lack of some of these anchor interactions delayed flap closure or impeded it
      completely, or even caused the flap to reopen. The methodology employed here
      could be used as a tool to evaluate future structural modifications which lead to
      improvements in the favorability and stability of BACE1-HEA ReLIEs, aiding in the
      design of better inhibitors.

PMID- 28746906
TI  - Prototyping for the treatment of late zygomatic-orbital fracture: A case report.
AB  - INTRODUCTION: Zygomatic-orbital complex fractures are the most common facial
      traumas that can result in severe esthetic and functional sequelae. Surgical
      correction of these fractures is a delicate approach and prototyping is an
      excellent tool to facilitate this procedure. PRESENTATION OF CASE: A 27-year-old
      man, a motorcycle accident victim, was hospitalized in the intensive care unit
      for 30days. After this period, facial fractures were treated surgically, leaving
      sequelae such as enophthalmos, dystopia and loss of projection of the zygomatic
      arch. A second intervention was planned after one year for reconstruction of the
      orbit with the help of prototyping. Better outcomes were achieved than in the
      first intervention. DISCUSSION: This report permits to compare the result of
      conventional surgery and the use of a prototype in the same patient. Noticeably
      better outcomes were achieved with the second approach. Prototyping made the
      surgical procedure more predictable and reduced operative time because of the
      possibility of using preshaped titanium plates. CONCLUSIONS: Prototyping was
      found to be an excellent option to overcome the deficiencies of the conventional
      technique, recovering the functional and esthetic characteristics of the
      patient's face and ensuring a markedly satisfactory outcome.

PMID- 28746907
TI  - Vibrational microspectroscopy analysis of human lenses.
AB  - In this study we present vibrational analysis of healthy (non-affected by
      cataract) and cataractous human lenses by means of Raman and FTIR spectroscopy
      methods. The performed analysis provides complex information about the secondary
      structure of the proteins and conformational changes of the amino acid residues
      due to the formation of opacification of human lens. Briefly, the changes in the
      conformation of the Tyr and Trp residues and the protein secondary structure
      between the healthy and cataractous samples, were recognized. Moreover, the
      observed spectral pattern suggests that the process of cataract development does
      not occur uniformly over the entire volume of the lens.

PMID- 28746908
TI  - Two-dimensional liquid chromatography in pharmaceutical analysis. Instrumental
      aspects, trends and applications.
AB  - The interest in two-dimensional liquid chromatography (2D-LC) has been growing up
      since the last decades. This promising technique appears as a relevant solution
      for various analytical challenges encountered in pharmaceutical analysis. The
      objective of this review is to give an overview of past, current and emerging
      trends in 2D-LC techniques applied to pharmaceutical compounds. The referenced
      studies cover the late 1980s to the present. Information regarding the different
      aspects of this analytical technique, including chromatographic conditions,
      instrumental setup and compounds of interest, was compiled and summarized into a
      synoptic table. Particular attention is paid to key features including (i) the
      interfaces used for coupling the two dimensions, (ii) the application fields, and
      (iii) the chromatographic modes that can be combined together. Finally an attempt
      is made to predict future advances in two-dimensional separation techniqes for
      pharmaceutical analysis.

PMID- 28746909
TI  - Optoelectronic iron detectors for pharmaceutical flow analysis.
AB  - Compact flow-through optoelectronic detectors fabricated by pairing of light
      emitting diodes have been applied for development of economic flow analysis
      systems dedicated for iron ions determination. Three analytical methods with
      different chromogens selectively recognizing iron ions have been compared.
      Ferrozine and ferene S based methods offer higher sensitivity and slightly lower
      detection limits than method with 1,10-phenantroline, but narrower ranges of
      linear response. Each system allows detection of iron in micromolar range of
      concentration with comparable sample throughput (20 injections per hour). The
      developed flow analysis systems have been successfully applied for determination
      of iron in diet supplements. The utility of developed analytical systems for iron
      release studies from drug formulations has also been demonstrated.

PMID- 28746910
TI  - Role of foam drainage in producing protein aggregates in foam fractionation.
AB  - It is essential to obtain a clear understanding of the foam-induced protein
      aggregation to reduce the loss of protein functionality in foam fractionation.
      The major effort of this work is to explore the roles of foam drainage in protein
      aggregation in the entire process of foam fractionation with bovine serum albumin
      (BSA) as a model protein. The results show that enhancing foam drainage increased
      the desorption of BSA molecules from the gas-liquid interface and the local
      concentration of desorbed molecules in foam. Therefore, it intensified the
      aggregation of BSA in foam fractionation. Simultaneously, it also accelerated the
      flow of BSA aggregates from rising foam into the residual solution along with the
      drained liquid. Because enhancing foam drainage increased the relative content of
      BSA molecules adsorbed at the gas-liquid interface, it also intensified the
      aggregation of BSA during both the defoaming process and the storage of the
      foamate. Furthermore, enhancing foam drainage more readily resulted in the
      formation of insoluble BSA aggregates. The results are highly important for a
      better understanding of foam-induced protein aggregation in foam fractionation.

PMID- 28746917
TI  - Cytological Features of the Large Cell Variant of Small Cell Ovarian Carcinoma in
      Young Patients with Hypercalcemia: Histological Findings and Review of the
      Literature.
AB  - OBJECTIVE: To present the cytological features of a very rare and lethal ovarian
      neoplasm occurring in the young. STUDY DESIGN: We reviewed the cytological
      findings as they presented in touch imprints obtained from an ovarian mass sent
      to our department for frozen section investigation. RESULTS: Smears were highly
      cellular. The cells were of intermediate size with a moderate amount of
      microvacuolated, pale, or eosinophilic cytoplasm with indistinct cell borders.
      The nuclei were of round or oval shape with mild to moderate atypia and
      indistinct nucleoli. CONCLUSIONS: The diagnosis of small cell carcinoma of the
      ovary can be challenging even histologically. Cytology can be an invaluable
      adjunct to hematoxylin-eosin sections both pre- or intraoperatively. Although it
      is a very rare occurrence and cytological results are almost absent in the
      literature, our case can make cytopathologists more acquainted with the
      cytological features of this rare tumor entity especially in association with a
      characteristic clinical profile. Furthermore, the cytological features of small
      cell carcinoma of the ovary, large cell variant, have only rarely been described
      in the literature.

PMID- 28746918
TI  - Differential Role of Rapamycin in Epidermis-Induced IL-15-IGF-1 Secretion via
      Activation of Akt/mTORC2.
AB  - : Backgroud/Aims: The effects of rapamycin (RPM) on wound healing have been
      previously studied. However, reciprocal contradictory data have been reported,
      and the underlying mechanism remains unclear. This study aims to uncover
      differential role of RPM in regulation of wound healing and explore the possible
      mechanism. METHODS: C57BL/6J mice and epidermal cells were treated with different
      doses of RPM. The wound re-epithelialization was observed by hematoxylin and
      eosin (HE) staining. The expression of IL-15 and IGF-1 were detected by
      immunohistochemistry and quantitative real-time PCR. Epidermal cell survival was
      determined by CCK-8 assays. Moreover, the mTORC1 and mTORC2 pathway were examined
      by western blot analysis. RESULTS: This study showed that differential doses of
      RPM could lead to separate consequences in epidermis. Histological analyses
      showed that low-dose RPM promoted wound healing, and enhanced the expression of
      IL-15 and IGF-1. Furthermore, western blot analysis showed that the effect of low
      dose RPM in epidermis were not through mTORC1 pathway. Instead, activation of the
      Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1
      production in epidermis, while high-dose RPM inhibited the expression of IL-15
      and IGF-1 and the activity of mTORC1 and mTORC2 pathway. CONCLUSION: This study
      for the first time demonstrated that RPM-mediated wound healing was dose
      dependent.

PMID- 28746919
TI  - C/EBPalpha Suppresses Lung Adenocarcinoma Cell Invasion and Migration by
      Inhibiting beta-Catenin.
AB  - BACKGROUND/AIMS: The transcription factor CCAAT/enhancer-binding protein alpha
      (C/EBPalpha) is a basic leucine zipper transcription factor that plays essential
      roles in tumor progression. Although decreased or absent C/EBPalpha expression in
      many cancers suggests a possible role for C/EBPalpha as a tumor suppressor, the
      functions of C/EBPalpha in lung adenocarcinoma remain unclear. METHODS: Here,
      C/EBPalpha expression levels in 26 lung adenocarcinoma and para-carcinoma tissue
      samples were detected by qRT-PCR and immunohistochemistry. Cell transwell assays,
      wound healing assay and three-dimensional spheroid invasion assay were performed
      to assess the effects of C/EBPalpha on migration and invasion in lung
      adenocarcinoma cells in vitro. Western blotting was applied to analyze the
      potential mechanisms. RESULTS: C/EBPalpha was found to be decreased in lung
      adenocarcinoma tissues compared to para-carcinoma tissues. Overexpression of
      C/EBPalpha significantly inhibited the migration and invasion of lung
      adenocarcinoma cells. In addition, C/EBPalpha overexpression suppressed the
      epithelial-mesenchymal transition (EMT) that was characterized by a gain of
      epithelial and loss of mesenchymal markers. Further study showed that C/EBPalpha
      suppressed the transcription of beta-catenin and downregulated the levels of its
      downstream targets. CONCLUSION: Our data suggest that C/EBPalpha inhibits lung
      adenocarcinoma cell invasion and migration by suppressing beta-catenin-mediated
      EMT in vitro. Thus, C/EBPalpha may be helpful as a potential target for treatment
      of lung adenocarcinoma.

PMID- 28746920
TI  - Assessing the Clinical Utility of SNP Microarray for Prader-Willi Syndrome due to
      Uniparental Disomy.
AB  - Maternal uniparental disomy (UPD) 15 is one of the molecular causes of Prader
      Willi syndrome (PWS), a multisystem disorder which presents with neonatal
      hypotonia and feeding difficulty. Current diagnostic algorithms differ regarding
      the use of SNP microarray to detect PWS. We retrospectively examined the
      frequency with which SNP microarray could identify regions of homozygosity (ROH)
      in patients with PWS. We determined that 7/12 (58%) patients with previously
      confirmed PWS by methylation analysis and microsatellite-positive UPD studies had
      ROH (>10 Mb) by SNP microarray. Additional assessment of 5,000 clinical
      microarrays, performed from 2013 to present, determined that only a single case
      of ROH for chromosome 15 was not caused by an imprinting disorder or identity by
      descent. We observed that ROH for chromosome 15 is rarely incidental and strongly
      associated with hypotonic infants having features of PWS. Although UPD
      microsatellite studies remain essential to definitively establish the presence of
      UPD, SNP microarray has important utility in the timely diagnostic algorithm for
      PWS.

PMID- 28746921
TI  - Effects of Transobturator Midurethral Sling Surgery on Sexual Functions: One-Year
      Follow-Up.
AB  - AIM: To evaluate sexual functions of women having stress urinary incontinence
      (SUI) preoperatively and 6 months and 12 months after undergoing a transobturator
      tape (TOT) +/- pelvic organ prolapse (POP) surgery. METHODS: One hundred-ninety
      five women with SUI +/- POP were recruited and 150 sexually active women who had
      clinical +/- urodynamic SUI and underwent TOT +/- POP surgery were included in
      this prospective study. Urogynecologic symptoms were evaluated preoperatively, at
      6 months, and 12 months by Female Sexual Function Index (FSFI). RESULTS: One
      hundred fifty women completed the study. Seventy-four underwent TOT-only and 76
      underwent TOT + concomitant surgery. Mean total scores of FSFI were 21.7 +/- 7.8,
      22 +/- 8.7, and 22.1 +/- 8 in the preoperative period, postoperative 6, and 12
      months, respectively. There was significant improvement in desire and total
      scores in the TOT-only group, whereas there was no significant difference in the
      TOT + concomitant surgery group except for significant worsening in the
      lubrication domain. The frequency of sexual intercourse increased while that of
      coital incontinence decreased after surgery. CONCLUSIONS: In our study, TOT was
      associated with decrease in coital incontinence and significant improvement in
      desire. In addition, there was significant improvement in FSFI desire and total
      scores in the TOT-only group, whereas no significant difference was observed in
      the TOT + concomitant surgery group except for the worsening of lubrication.

PMID- 28746922
TI  - Effects of PKM2 Gene Silencing on the Proliferation and Apoptosis of Colorectal
      Cancer LS-147T and SW620 Cells.
AB  - BACKGROUND/AIMS: This paper aims to explore the effects of pyruvate kinase (PK)
      M2 gene silencing on the proliferation and apoptosis of colorectal cancer (CRC)
      LS-147T and SW620 cells. METHODS: CRC LS-147T and SW620 cells highly expressing
      PKM2 were randomly selected by quantitative real-time polymerase chain reaction
      (qRT-PCR) and then assigned into the blank (no transfection), PKM2-shRNA
      (transfection with shRNA) and empty plasmid (transfection with empty plasmid)
      groups. Immunofluorescence was applied to detect PKM2 protein expression. qRT-PCR
      and Western blotting were conducted to assess mRNA and protein expression of
      PKM2, p53 and p21. The cell counting kit-8 (CCK-8) assay was used to assess cell
      proliferation. Flow cytometry was used to assess the cell cycle and apoptosis
      rate, and a senescence-associated beta-galactosidase staining kit was used to
      assess cell senescence. RESULTS: PKM2 exhibited high mRNA expression among CRC LS
      147T and SW620 cells with remarkable protein expression noted in the cytoplasm
      and nucleus. The PKM2-shRNA group exhibited reduced PKM2 mRNA and protein
      expression, whereas p53 and p21 expression was increased compared with the blank
      and empty plasmid groups. Cell proliferation in PKM2-shRNA cells decreased
      significantly compared with the blank group and empty plasmid groups. The PKM2
      shRNA group exhibited more cells in the G1 phase and fewer cells in the G2/M
      phase compared with the blank and empty plasmid groups. In addition, the PKM2
      shRNA group exhibited significantly increased apoptosis rates and beta
      galactosidase activity compared with the blank and empty plasmid groups.
      CONCLUSION: Our study demonstrates that PKM2 gene silencing suppresses
      proliferation and promotes apoptosis in LS-147T and SW620 cells.

PMID- 28746923
TI  - Parkinsonian Patients with Striatal Cribriform State Present Rapidly Progressive
      Axial Parkinsonism.
AB  - OBJECTIVE: To define the significance of striatal cribriform state (SCS) observed
      in patients with primary progressive parkinsonism. METHODS: We reviewed medical
      records and brain magnetic resonance imaging studies of 1,260 patients with
      primary progressive parkinsonism. We identified 23 patients with SCS and analyzed
      their clinical features. RESULTS: All 23 patients had rapidly progressive
      parkinsonism predominated by postural instability and gait disturbance. Clinical
      features of 18 of the 23 patients were compatible with progressive supranuclear
      palsy (PSP); 2 patients were compatible with parkinsonian type multiple system
      atrophy; 2 patients were compatible with mixed clinical features of both; and 1
      patient had PSP-like clinical features. CONCLUSIONS: Most parkinsonian patients
      with SCS present rapidly progressive parkinsonism predominated by postural
      instability and gait disturbance. SCS observed in patients with parkinsonism does
      not seem to be a coincidental finding associated with the generalized
      cerebrovascular process.

PMID- 28746924
TI  - Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1 Facilitates the Development of
      Cardiac Hypertrophy.
AB  - BACKGROUND/AIMS: Adult cardiomyocytes can re-enter cell cycle as stimulated by
      prohypertrophic factors although they withdraw from cell cycle soon after birth.
      p21WAF1/CIP1, a cyclin-dependent kinase inhibitor, has been implicated in cardiac
      hypertrophy, however, its precise contribution to this process remains largely
      unclear. METHODS: The gene expression profile in left ventricle (LV) of
      spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined
      using quantitative PCR array and verified by real-time PCR and Western blotting.
      Hypertrophic response of H9c2 cells and neonatal rat ventricular myocytes (NRVM)
      were induced by angiotensin II (1 umol/L). Cardiac hypertrophy of mice was
      elicited by isoproterenol (ISO) infusion (40 mg/kg per day for 14 days). p21
      adenovirus and p21-siRNA were employed to transfect NRVM, and sterigmatocystin
      (STE, 3 mg/kg, ip, qd) was used to inhibit p21 activity. mRNA and protein
      expression levels of alpha- and beta-myosin heavy chain (MHC), p21WAF1/CIP1,
      calcineurin (CaN) and atrial natriuretic peptide (ANP) were assayed by realtime
      PCR and WB, respectively. RESULTS: Sixteen genes showed two-fold or greater
      changes between SHR and WKY rats, in which the expression of p21WAF1/CIP1 was
      upregulated by 4.15-fold (P=0.002) and reversed by losartan. Surface area,
      protein content, mRNA and protein expressions of beta-MHC, ANP and p21WAF1/CIP1
      in H9c2 cells treated with AngII elevated significantly compared with control
      group. p21-Ad transfection markedly increased the surface area and beta-MHC mRNA
      expression of normal NRVMs, and p21-siRNA transfection decreased them in AngII
      treated NRVMs. STE treatment decreased HW/BW and cross-sectional area, expression
      levels of beta-MHC, ANP and p21 significantly in ISO-treated mice. CONCLUSION:
      Our findings suggest that p21 facilitates the development of cardiac hypertrophy,
      and regulating the expression of p21 may be an approach to attenuate hypertrophic
      growth of cardiomyocytes.

PMID- 28746925
TI  - Pulmonary Arteriovenous Malformations Are Associated with Silent Brain Infarcts
      in Hereditary Hemorrhagic Telangiectasia Patients.
AB  - BACKGROUND AND PURPOSE: There is a high prevalence of right-to-left shunting
      pulmonary arteriovenous malformations (PAVMs), which are stroke risk factors, in
      hereditary hemorrhagic telangiectasia (HHT) patients. While the prevalence of
      ischemic complications in HHT patients is known, the prevalence of silent brain
      infarcts (SBI) remains unknown. The purpose of this study was to determine the
      prevalence and risk factors for SBI in HHT patients. MATERIALS AND METHODS: Our
      institutional HHT database was queried to identify HHT patients who received a
      baseline screening brain MRI from January 2000 to February 2017. This study group
      was further refined by excluding patients who had a history of clinical ischemic
      disease as defined by having a stroke or transient ischemic attack (TIA). Brain
      MRIs were reviewed for SBI. Baseline data on demographics, Curacao criteria,
      presence of PAVMs, and cardiovascular risk factors were collected. The primary
      outcome was SBI prevalence. We also examined which baseline patient
      characteristics were associated with SBI through univariate chi-square and
      Student t tests and multivariate logistic regression analyses. RESULTS: Three
      hundred fifty three consecutive HHT patients from January 2000 to February 2017
      with a screening brain MRI and no prior history of stroke/TIA were included. SBI
      prevalence was 9.9% (35/353). SBI patients were more likely to have PAVMs than
      non-SBI patients (80.6 vs. 53.1%, p = 0.005). The median age was 66 in the SBI
      group and 52 in the non-SBI group (p = 0.006). SBI patients had higher prevalence
      of hyperlipidemia (34.3 vs. 9.8%, p < 0.0001), hypertension (48.6 vs. 22.0%, p =
      0.005), and tobacco use (25.7 vs. 9.8%, p = 0.005). No patients under 30 had SBI.
      In the 60-69 age group, the prevalence of SBI was 18.8% with rates of 28.6% in
      the PAVM group and 10.5% in the non-PAVM group. For patients >=70 years old, the
      prevalence of SBI was 21.4% overall and 27.6% in the PAVM group and 10.5% in the
      non-PAVM group. On multivariate analysis, PAVMs (OR 3.62, 95% CI 1.46-10.40) and
      increasing age (OR 1.04, 95% CI 1.01-1.07) were independently associated with
      SBI. CONCLUSIONS: Overall, a similar 10% SBI prevalence in the HHT cohort was
      noted as compared to the general population. However, the prevalence of SBI was
      higher in HHT patients with PAVMs when compared to that of the general
      population, particularly among patients than 60 years old. These findings
      highlight the need to accurately identify, and when appropriate, treat PAVMs in
      the HHT population especially given the multiple significant, clinical
      consequences of SBI.

PMID- 28746926
TI  - Histamine Iontophoresis as in vivo Model to Study Human Skin Inflammation with
      Minimal Barrier Impairment: Pilot Study Results of Application of the Model to a
      Sensitive Skin Panel.
AB  - BACKGROUND/AIMS: Histamine iontophoresis is known to elicit itch and a wheal-and
      flare reaction; however, its impact on the skin barrier and underlying
      compartments has not been thoroughly evaluated yet. The primary objective of this
      study was to characterize that using immunohistochemistry, biophysical
      measurements, and image analysis, and secondly, to explore whether skin reactions
      to this model differ in sensitive skin (SS). METHODS: Eighteen healthy subjects,
      n = 9 with SS and n = 9 with non-sensitive skin (NSS), were included based on a
      perception-based questionnaire. Histamine iontophoresis was performed on the
      buttock, and skin reactions were evaluated up to 72 h after stimulation. RESULTS:
      The wheal-and-flare peaked at 30 min; after 8 h, no clinical signs were visible.
      No signs of disruption of the stratum corneum, as well as no increase in the
      number of Ki67-positive cells emerged, whereas fewer tryptase-positive mast cells
      and increased epidermal thickness were observed at 1 and 72 h, respectively. SS
      subjects showed higher perception of itch compared to NSS subjects. CONCLUSION:
      Histamine iontophoresis is a well-standardized in vivo model to quantitatively
      study the early stages of cutaneous inflammation with minimal impact on the skin
      barrier. In line with previous studies, it highlighted increased sensory
      perceptions in SS.

PMID- 28746927
TI  - Autologous Adipose Tissue Graft to Treat Hypertensive Leg Ulcer: A Pilot Study.
AB  - BACKGROUND: Adipose tissue is an abundant source of mesenchymal stem cells,
      called adipose-derived stem cells, which have anti-inflammatory and trophic
      effects to enhance overall tissue repair. OBJECTIVE: To determine the healing
      effects of autologous adipose tissue graft on hypertensive leg ulcers. METHODS:
      Prospective pilot study in 1 French dermatology department. Ten patients with a
      hypertensive leg ulcer were enrolled from April 2013 to June 2015. The primary
      end point was the wound closure rate at each follow-up visit. The secondary end
      points were wound characteristics, pain assessment and adverse events. RESULTS:
      One patient, the only smoker, was lost to follow-up at month 5 (M5). For the 9
      non-smokers, wound surfaces constantly and significantly decreased: the median
      wound closure rate was 73.2% at M3 and 93.1% at M6, p < 0.001. The median wound
      closure rate of the 10 patients was 63.2% at M3, p < 0.001. Percentages of fibrin
      and necrosis decreased, granulation tissue increased significantly. Pain rapidly
      and significantly decreased. No recurrence or adverse event was observed.
      CONCLUSION: Our data suggest that autologous adipose tissue grafting induces pain
      relief and promotes wound healing with a good skin quality. Large prospective
      controlled randomized studies are required to confirm these results.

PMID- 28746928
TI  - Diagnostic Performance of Cerebroplacental Ratio Thresholds at Term for
      Prediction of Low Birthweight and Adverse Intrapartum and Neonatal Outcomes in a
      Term, Low-Risk Population.
AB  - OBJECTIVES: To investigate the screening performance and best threshold centile
      (5th vs. 10th) of the cerebroplacental ratio (CPR) in low-risk, term pregnancies
      to predict low birthweight and adverse intrapartum and neonatal outcomes in a
      term, low-risk population. METHODS: This was a blinded, prospective, cross
      sectional study of low-risk singleton pregnancies at term. Women attended
      fortnightly from 36 weeks for CPR and estimated fetal weight assessment.
      Intrapartum and neonatal outcomes were recorded. Primary outcomes assessed were
      low birthweight, cesarean section for intrapartum fetal compromise, and composite
      adverse neonatal outcome. RESULTS: A total of 483 women participated in the
      study. The CPR 10th centile (1.48) threshold resulted in the best screening
      performance. Sensitivities for low birthweight, cesarean section for intrapartum
      fetal compromise, and composite adverse neonatal outcome of 41.9, 61.1, and 38.3%
      were achieved for false-positive rates of 17.7, 17.7, and 15.2%, respectively.
      The corresponding areas under the receiver operating characteristic curves were
      0.62, 0.72, and 0.62. CONCLUSION: The CPR 10th centile resulted in the best
      screening performance, although this would be considered fair at best. The CPR
      10th centile may be useful as part of a risk stratification tool for prediction
      of low birthweight and adverse intrapartum and neonatal outcomes.

PMID- 28746929
TI  - Excessive Maternal Orange Intake - A Reversible Etiology of Fetal Premature
      Ductus Arteriosus Constriction: A Case Report.
AB  - Ductus arteriosus (DA) is a crucial element in the fetal circulation. Therefore,
      premature constriction of DA during the third trimester can have hazardous
      complications such as right ventricular dysfunction, fetal heart failure,
      hydrops, and even in utero demise. Normally, premature constriction is prevented
      by a balance between prostaglandin E2 and fetal oxygenation. Thus, drugs with
      antiprostaglandin effects are well-known causes for fetal DA constriction. A
      similar effect was discovered in eating polyphenol-rich food. Here, we report a
      case of early-detected fetal DA constriction due to a high maternal ingestion of
      fresh oranges, which are known to be rich in polyphenols. This effect was totally
      reversed 2 weeks after eliminating oranges from the maternal diet. From the
      current report, it is concluded that restrictions in the maternal diet regarding
      polyphenol-rich foods such as oranges can be considered during the third
      trimester to prevent the harmful effect on DA.

PMID- 28746930
TI  - Cocultivation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Reveals
      Antiapoptotic and Proangiogenic Effects.
AB  - Integrating bioartificial tissues into the host vasculature is a prerequisite for
      tissue engineering applications. Endothelial progenitor cells (EPCs) display a
      high angiogenic potential and a low donor-site morbidity, making them ideal for
      tissue engineering applications. In our study we used a murine EPC cell line
      (T17b) and rat mesenchymal stem cells (MSCs) for cocultivation experiments. MSCs
      were cocultured with increasing T17b EPC amounts. Furthermore, MSCs in
      monoculture were treated with conditioned medium (CM) from T17b EPCs and T17b
      EPCs were treated with CM from MSCs. Proliferation and apoptosis were quantified
      with a bromodeoxyuridine ELISA and a DNA fragmentation ELISA, respectively.
      Osteogenic differentiation was detected with an alkaline phosphatase assay and
      bone morphogenetic protein-2 ELISA. The production of proangiogenic molecules was
      measured with a matrix metalloproteinase-3 and vascular endothelial growth factor
      ELISA as well as nitric oxide assay. We could show that T17b EPCs stimulated MSC
      proliferation but not vice versa. On the other hand, MSCs promoted the cell
      survival of EPCs. The growth-inducing and antiapoptotic effects were dependent on
      heterotypic cell contacts and paracrine mediators. Moreover, proangiogenic growth
      factors were found in the coculture. Collectively, our results indicate that the
      coapplication of MSCs and T17b EPCs provides new perspectives for tissue
      engineering applications.

PMID- 28746931
TI  - Treatment Outcomes for Metastatic Melanoma of Unknown Primary in the New Era: A
      Single-Institution Study and Review of the Literature.
AB  - BACKGROUND: Metastatic melanoma of unknown primary (MUP) is uncommon,
      biologically ill defined, and clinically understudied. MUP outcomes are seldom
      reported in clinical trials. In this study, we analyze responses of MUP patients
      treated with systemic therapy in an attempt to inform treatment guidelines for
      this unique population. METHODS: New York University (NYU)'s prospective melanoma
      database was searched for MUP patients treated with systemic therapy. PubMed and
      Google Scholar were searched for MUP patients treated with immunotherapy or
      targeted therapy reported in the literature, and their response and survival data
      were compared to the MUP patient data from NYU. Both groups' response data were
      compared to those reported for melanoma of known primary (MKP). RESULTS: The MUP
      patients treated at NYU had better outcomes on immunotherapy but worse on
      targeted therapy than the MUP patients in the literature. The NYU MUP patients
      and those in the literature had worse outcomes than the majority-MKP populations
      in 10 clinical trial reports. CONCLUSIONS: Our study suggests that MUP patients
      might have poorer outcomes on systemic therapy as compared to MKP patients. Our
      cohort was small and limited data were available, highlighting the need for
      increased reporting of MUP outcomes and multi-institutional efforts to understand
      the mechanism behind the observed differences.

PMID- 28746932
TI  - Morbidity and Functional Outcomes following Free Jejunal Flap Reconstruction for
      Head and Neck Cancer.
AB  - AIM: To evaluate the morbidity and fundamental functional outcomes (swallow and
      speech) after free jejunal flap (FJF) reconstruction following total
      pharyngolaryngo-esophagectomy (PLE) in China. METHODS: 18 patients with FJF
      reconstruction after total PLE were retrospectively reviewed. Scheduled barium
      swallow test was performed 7-10 days postoperatively. Rehabilitation of
      swallowing and speech for patients was assessed by the Performance Status Scale
      for Head and Neck Cancer Patients. RESULTS: 8 patients died of tumor recurrence
      and 2 patients died of other reasons (cerebrovascular disease and respiratory
      disease, respectively). The 1-year, 2-year, and 3-year survival rates were 70.5,
      49.4, and 33.8%, respectively. 83.3% of all patients could tolerate soft chewable
      foods, such as cooked vegetables, fish, hamburger, and small pieces of meat. 2
      patients with early stenosis at upper anastomotic sites were with good swallowing
      function; while 2 patients with early stenosis at lower anastomotic sites were
      found to have difficulty in oral diet. 2 (11.1%) patients with larynx-preserving
      pharyngo-esophagectomy showed no compromise in speech. Only 2 (11.1%) patients
      underwent primary tracheoesophageal puncture for inserting an indwelling voice
      prosthesis for speech, and both patients achieved functional tracheoesophageal
      speech. The remaining 14 (77.8%) patients with total PLE did not resume
      functional speech. CONCLUSION: Postoperative barium swallow examination is
      helpful to predict long-term anastomotic stenosis. Good functional swallow
      rehabilitation is achieved following FJF reconstruction after total PLE or a
      larynx-preserving procedure. However, the speech outcomes are not satisfactory.
      It raises the demand of enhancement of functional recovery so that quality of
      life can be improved for these patients in China.

PMID- 28746933
TI  - Androgen Regulates Dimorphic F-Actin Assemblies in the Genital Organogenesis.
AB  - Impaired androgen activity induces defective sexual differentiation of the male
      reproductive tract, including hypospadias, an abnormal formation of the penile
      urethra. Androgen signaling in the urethral mesenchyme cells (UMCs) plays
      essential roles in driving dimorphic urethral development. However, cellular
      events for sexual differentiation remain virtually unknown. In this study,
      histological analyses, fluorescent staining, and transmission electron microscopy
      (TEM) were performed to reveal the cellular dimorphisms of UMCs. F-actin dynamics
      and migratory behaviors of UMCs were further analyzed by time-lapse imaging. We
      observed a prominent accumulation of F-actin with poorly assembled extracellular
      matrix (ECM) in female UMCs. In contrast, thin fibrils of F-actin co-aligning
      with the ECM through membrane receptors were identified in male UMCs. Processes
      for dimorphic F-actin assemblies were temporally identified during an androgen
      regulated masculinization programming window and spatially distributed in several
      embryonic reproductive tissues. Stage-dependent modulation of the F-actin sexual
      patterns by androgen in UMCs was also demonstrated by time-lapse analysis.
      Moreover, androgen regulates coordinated migration of UMCs. These results suggest
      that androgen signaling regulates the assembly of F-actin from cytoplasmic
      accumulation to membranous fibrils. Such alteration appears to promote the ECM
      assembly and the mobility of UMCs, contributing to male type genital
      organogenesis.

PMID- 28746934
TI  - Protective Effects of Salvianolate on Contrast-Induced Nephropathy after Primary
      Percutaneous Coronary Intervention: A Prospective Multicenter Randomized
      Controlled Trial.
AB  - OBJECTIVES: This study's aim was to evaluate the protective effects of
      salvianolate on contrast-induced nephropathy after primary percutaneous coronary
      intervention (PPCI) compared with normal saline (NS) hydration. METHODS: We
      enrolled patients with acute myocardial infarction who underwent PPCI in 3
      centers in Shanghai. The patients were randomly assigned to the salvianolate
      group or the NS group. The incidence of CIN, the changes in renal function
      parameters, and the occurrence of adverse events after the procedure were
      compared between the 2 groups. We used a multivariate logistic regression
      analysis to determine the independent correlates of CIN after PPCI. RESULTS: A
      total of 484 patients were finally included in the statistical analysis. Compared
      with the control group, salvianolate reduced the incidence of CIN (9.1 vs. 16.3%,
      p = 0.018) after PPCI. The renal function parameters after PPCI in the
      salvianolate group were superior to those of the control group (p < 0.05). The
      composite adverse events rate was significantly lower in the salvianolate group
      within 1 month after the procedure (9.5 vs. 15.5%, p = 0.046). A higher peak of
      troponin I and loop diuretic therapy were the independent correlates of CIN after
      PPCI. CONCLUSIONS: Salvianolate reduces the incidence of CIN and protects renal
      function after PPCI, and the effects were superior to those of NS hydration.

PMID- 28746935
TI  - Maintaining Distinctiveness at Increased Speaking Rates: A Comparison between
      Congenitally Blind and Sighted Speakers.
AB  - OBJECTIVES: The effects of increased speaking rates on vowels have been well
      documented in sighted adults. It has been reported that in fast speech, vowels
      are less widely spaced acoustically than in their citation form. Vowel space
      compression has also been reported in congenitally blind speakers. The objective
      of the study was to investigate the interaction of vision and speaking rate in
      adult speakers. PATIENTS AND METHODS: Contrast distances between vowels were
      examined in conversational and fast speech produced by 10 congenitally blind and
      10 sighted French-Canadian adults. Acoustic analyses were carried out. RESULTS:
      Compared with the sighted speakers, in the fast speaking condition, the blind
      speakers produced more vowels with contrast along the height, place of
      articulation, and rounding features located within the auditory target regions
      typical of French vowels. CONCLUSION: Blind speakers relied more heavily than
      sighted speakers on auditory properties of vowels to maintain perceptual
      distinctiveness.

PMID- 28746936
TI  - Defining Standards in Experimental Microsurgical Training: Recommendations of the
      European Society for Surgical Research (ESSR) and the International Society for
      Experimental Microsurgery (ISEM).
AB  - BACKGROUND: Expectations towards surgeons in modern surgical practice are
      extremely high with minimal complication rates and maximal patient safety as
      paramount objectives. Both of these aims are highly dependent on individual
      technical skills that require sustained, focused, and efficient training outside
      the clinical environment. At the same time, there is an increasing moral and
      ethical pressure to reduce the use of animals in research and training, which has
      fundamentally changed the practice of microsurgical training and research.
      Various animal models were introduced and widely used during the mid-20th
      century, the pioneering era of experimental microsurgery. Since then, high
      numbers of ex vivo training concepts and quality control measures have been
      proposed, all aiming to reduce the number of animals without compromising quality
      and outcome of training. SUMMARY: Numerous microsurgical training courses are
      available worldwide, but there is no general agreement concerning the
      standardization of microsurgical training. The major aim of this literature
      review and recommendation is to give an overview of various aspects of
      microsurgical training. We introduce here the findings of a previous survey-based
      analysis of microsurgical courses within our network. Basic principles behind
      microsurgical training (3Rs, good laboratory practice, 3Cs), considerations
      around various microsurgical training models, as well as several skill assessment
      tools are discussed. Recommendations are formulated following intense discussions
      within the European Society for Surgical Research (ESSR) and the International
      Society for Experimental Microsurgery (ISEM), based on scientific literature as
      well as on several decades of experience in the field of experimental
      (micro)surgery and preclinical research, represented by the contributing authors.
      Key Messages: Although ex vivo models are crucial for the replacement and
      reduction of live animal use, living animals are still indispensable at every
      level of training which aims at more than just a basic introduction to
      microsurgical techniques. Modern, competency-based microsurgical training is
      multi-level, implementing different objective assessment tools as outcome
      measures. A clear consensus on fundamental principles of microsurgical training
      and more active international collaboration for the sake of standardization are
      urgently needed.

PMID- 28746937
TI  - Prevalence, Duration and Severity of Parkinson's Disease in Germany: A Combined
      Meta-Analysis from Literature Data and Outpatient Samples.
AB  - BACKGROUND: Epidemiological data on the prevalence of Parkinson's disease (PD) in
      Germany are limited. The aims of this study were to estimate the age- and gender
      specific prevalence of PD in Germany as well as the severity and illness
      duration. SUMMARY: A systematic literature search was performed in 5 different
      databases. European studies were included if they reported age- and gender
      specific numbers of prevalence rates of PD. Meta-analytic approaches were applied
      to derive age- and gender-specific pooled prevalence estimates. Data of 4 German
      outpatient samples were incorporated to calculate the proportion of patients with
      PD in Germany grouped by Hoehn and Yahr (HY) stages and disease duration. In the
      German population, 178,169 cases of PD were estimated (prevalence:
      217.22/100,000). The estimated relative illness duration was 40% with less than 5
      years, 31% with 5-9 years, and 29% with more than 9 years. The proportions for
      different HY stages were estimated at 13% (I), 30% (II), 35% (III), 17% (IV), and
      4% (V), respectively. Key Message: We provide an up-to-date estimation of age-
      and gender-specific as well as severity-based prevalence figures for PD in
      Germany. Further community studies are needed to estimate population-based
      severity distributions and distributions of non-motor symptoms in PD.

PMID- 28746938
TI  - Magnolol Inhibits the Growth of Non-Small Cell Lung Cancer via Inhibiting
      Microtubule Polymerization.
AB  - BACKGROUND: The tubulin/microtubule system, which is an integral component of the
      cytoskeleton, plays an essential role in mitosis. Targeting mitotic progression
      by disturbing microtubule dynamics is a rational strategy for cancer treatment.
      METHODS: Microtubule polymerization assay was performed to examine the effect of
      Magnolol (a novel natural phenolic compound isolated from Magnolia obovata) on
      cellular microtubule polymerization in human non-small cell lung cancer (NSCLC)
      cells. Cell cycle analysis, mitotic index assay, cell proliferation assay, colony
      formation assay, western blotting analysis of cell cycle regulators, Annexin V
      FITC/PI staining, and live/dead viability staining were carried out to
      investigate the Magnolol's inhibitory effect on proliferation and viability of
      NSCLS cells in vitro. Xenograft model of human A549 NSCLC tumor was used to
      determine the Magnolol's efficacy in vivo. RESULTS: Magnolol treatment
      effectively inhibited cell proliferation and colony formation of NSCLC cells.
      Further study proved that Magnolol induced the mitotic phase arrest and inhibited
      G2/M progression in a dose-dependent manner, which were mechanistically
      associated with expression alteration of a series of cell cycle regulators.
      Furthermore, Magnolol treatment disrupted the cellular microtubule organization
      via inhibiting the polymerization of microtubule. We also found treatment with
      NSCLC cells with Magnolol resulted in apoptosis activation through a p53
      independent pathway, and autophgy induction via down-regulation of the Akt/mTOR
      pathway. Finally, Magnolol treatment significantly suppressed the NSCLC tumor
      growth in mouse xenograft model in vivo. CONCLUSION: These findings identify
      Magnolol as a promising candidate with anti-microtubule polymerization activity
      for NSCLC treatment.

PMID- 28746939
TI  - Consistency between Targets Delineated by Angiography, Computed Tomography, and
      Magnetic Resonance Imaging in Stereotactic Radiosurgery for Arteriovenous
      Malformation.
AB  - BACKGROUND: Target identification is important for radiosurgery for arteriovenous
      malformations (AVMs). Targets defined by different imaging modalities may be
      inconsistent in practice. OBJECTIVES: The goal of this study is to review and
      analyze the consistency between targets defined by different imaging modalities
      in radiosurgery for AVMs. METHODS: From March 2007 to June 2011, AVM patients for
      radiosurgery whose targets were delineated by angiography/computed tomography
      (CT)/magnetic resonance imaging (MRI) were reviewed. Spetzler-Martin grades,
      hemorrhage history, and treatment volumes were checked. Dice similarity
      coefficients (DSCs) between targets were calculated and analyzed. RESULTS: Twenty
      three patients were enrolled. The mean DSCs were between 0.37 and 0.51 for
      targets by different modalities. There was no significant difference in DSCs
      regarding Spetzler-Martin grades and hemorrhage history. For CT-delineated target
      volumes <3 cm3, MRI-delineated target volumes <5 cm3, and angiography-delineated
      target volumes <2 cm3, the DSCs between the different image modalities were
      significantly decreased. CONCLUSIONS: Consistency between targets delineated
      using different image modalities was likely to be unsatisfactory and worsen
      significantly in niduses with volumes <5 cm3. An iterative multimodality approach
      to confirm the delineated targets of AVMs is suggested to be indispensable for
      robust treatment in radiosurgery.

PMID- 28746940
TI  - Comparison of the Skin Penetration of 3 Metabolically Stable Chemicals Using
      Fresh and Frozen Human Skin.
AB  - BACKGROUND: The Cosmetics Europe ADME Task Force is developing in vitro and in
      silico tools for predicting skin and systemic concentrations after topical
      application of cosmetic ingredients. There are conflicting reports as to whether
      the freezing process affects the penetration of chemicals; therefore, we
      evaluated whether the storage of human skin used in our studies (8-12 weeks at 
      20 degrees C) affected the penetration of model chemicals. METHODS: Finite doses
      of trans-cinnamic acid (TCA), benzoic acid (BA), and 6-methylcoumarin (6MC) (non
      volatile, non-protein reactive and metabolically stable in skin) were applied to
      fresh and thawed frozen skin from the same donors. The amounts of chemicals in
      different skin compartments were analysed after 24 h. RESULTS: Although there
      were some statistical differences in some parameters for 1 or 2 donors, the
      penetration of TCA, BA, and 6MC was essentially the same in fresh and frozen
      skin, i.e., there were no biologically relevant differences in penetration
      values. Statistical differences that were evident indicated that penetration was
      marginally lower in frozen than in fresh skin, indicating that the barrier
      function of the skin was not lost. CONCLUSION: The penetration of the 3 chemicals
      was essentially unaffected by freezing the skin at -20 degrees C for up to 12
      weeks.

PMID- 28746941
TI  - Occurrence of Cranial Neoplasms in Pediatric Patients with Noonan Syndrome
      Receiving Growth Hormone: Is Screening with Brain MRI prior to Initiation of
      Growth Hormone Indicated?
AB  - Noonan syndrome (NS) is associated with short stature. Growth hormone treatment
      has been FDA approved for use in these patients. Children with NS are at a higher
      risk of developing benign and malignant proliferative disorders, primary brain
      tumors being one of them. Since growth hormone therapy can worsen the tumor
      burden, screening with a brain MRI prior to growth hormone initiation in NS
      patients is strongly recommended. Here we present two NS patients who developed
      different primary brain tumors while being on growth hormone therapy.

PMID- 28746942
TI  - Screening for Retinopathy of Prematurity: Insight into Optimizing Screening.
AB  - PURPOSE: To determine the factors influencing the time from preterm birth and
      retinopathy of prematurity (ROP) detection to optimize the timing of the initial
      screening. METHODS: This multicenter retrospective study enrolled preterm infants
      born before 32 weeks of gestational age (GA) and/or weighing less than 1,500 g
      between January 1, 2011, and December 31, 2015. ROP screening was performed using
      fundus photography with a wide-field camera. Population and follow-up
      characteristics were recorded. RESULTS: Among the 1,266 preterm infants observed,
      795 were retained for analysis. One hundred seventy-four (21.6%) cases of ROP
      were detected with the first examination performed at 32.3 +/- 1.6 weeks of
      postmenstrual age (PMA) and 5.4 +/- 1.0 weeks of postnatal age (PNA). The first
      signs of ROP were detected at 34.0 +/- 1.9 weeks of PMA and 7.2 +/- 1.8 weeks of
      PNA, respectively. In the multivariate analysis, an older GA, a longer duration
      of mechanical ventilation, and a lower birth weight were correlated with a longer
      time between preterm birth and ROP detection (p < 0.0001, p < 0.0001, and p =
      0.0359, respectively). CONCLUSION: The first examination for ROP screening should
      be individualized to fit the first screening examination as closely as possible
      to the first signs of ROP in order to avoid unnecessary examinations without
      missing ROP.

PMID- 28746943
TI  - Identification of 3 Novel Patients with CLCN2-Related Leukoencephalopathy due to
      CLCN2 Mutations.

PMID- 28746944
TI  - Erratum.

PMID- 28746946
TI  - Endocrine Factors Determining Immune Polarization during Perinatal Transition.
AB  - In utero the skewness of the adaptive immune system towards Th2
      ('antiinflammatory') direction and low of Th1/Th2 cell ratio defend the fetus
      against rejection by the maternal immune system. Th2 dominance at birth is also
      of importance as it prevents uncontrolled inflammatory processes during
      parturition. This condition should change rapidly after birth. In an extrauterine
      milieu that is inherent with exposure to microorganisms, Th1 ('proinflammatory')
      polarization (i. e. increased Th1 cytokine production along with high Th1/Th2
      ratio) are required to maintain an efficient immune response. After birth,
      maternal hormone supplies including estrogen, progesterone, testosterone, and
      antiinflammatory prostaglandins cease abruptly. As these hormones have an immune
      modulatory action favoring Th2, and inhibiting Th1 polarization, their low level
      supports the strengthening of Th1-type immunity. During parturition a dramatic
      but transient increase of several hormones (oxytocin, thyorid hormones, and
      catecholamines) occurs. Again, the net effect of high hormone levels favors Th2
      activation, followed by Th1 polarization when hormonal levels reach their
      postnatal levels. The perinatal change of these components results in the quick
      cessation of Th1 inhibition and supports the maturation of adaptive immunity to
      provide an effective response against extrauterine microorganisms.

PMID- 28746947
TI  - [Eccentric Training after a Traumatic Apophysis Fracture at the Spina Iliaca
      Anterior Inferior: Case Study of a Junior Football Player].
AB  - Eccentric training is an established training method in competitive sports. It
      has been used effectively to improve muscle strength during rehabilitation after
      cruciate ligament reconstruction. However, it is still uncertain whether or not
      eccentric training contributes to successful rehabilitation after apophysis
      fractures. A fourteen-year-old soccer player, forward position, presents with an
      apophysis avulsion located at the right spina iliaca anterior inferior. After
      completing an early rehabilitation phase and isokinetic concentric strength
      development, the patient starts an eccentric training programme eight weeks after
      the injury, including training on an isokinetic dynamometer (Biodex) for four
      weeks, followed by a four-week eccentric ergometer training (Eccentron). Before
      and after each eccentric training phase, isokinetic maximum strength tests of the
      knee extensors and flexors are performed with angular velocities of 60 degrees
      per second ( degrees /sec.), 180 degrees /sec. and 240 degrees /sec. In response
      to the eight-week eccentric rehabilitation program, maximum torque increases in
      all angular velocities in the injured (60 degrees /sec. + 14.4 %; 180 degrees
      /sec. + 8.8 %; 240 degrees /sec. + 6.3 %) and the uninjured leg (60 degrees /sec.
      + 15.6 %; 180 degrees /sec. + 1.9 %; 240 degrees /sec. + 8.1 %) between the first
      and the last test. Furthermore, neuromuscular coordination has improved during
      the eccentric training sessions. This case study demonstrates that controlled
      eccentric training in the open and closed kinetic chain increases coordination
      and strength of the trained muscles and therefore should be regarded as a
      valuable contribution toward a safe return to sport after apophysis fractures.

PMID- 28746948
TI  - [Factors Associated with Safety Knowledge on Alpine Ski Slopes].
AB  - Background The jurisdiction after a winter sport accident including a third party
      fault considers the 10 rules for safe skiing/snowboarding introduced by the
      International Ski Federation (FIS) to clarify the question of liability. A
      previous study revealed that beginners, young skiers and those who were not local
      residents displayed insufficient safety knowledge in given situations. The aim of
      this study was to evaluate additional factors associated with safety knowledge on
      ski slopes, e. g. type of winter sport, helmet use, risk taking behavior, and a
      previous injury occurred on a ski slope. Methods People participating in snow
      sports were interviewed in March 2012 during 2 weekends in 5 Austrian ski areas,
      using a standardised questionnaire. Participants had to correctly answer 12
      statements according to safety knowledge based on the 10 FIS rules. Results A
      total of 602 persons (67 % skiers) with a mean age of 32.8 +/- 14.6 (Range: 8 -
      77) years were interviewed. In total, 12 and 11 statements were correctly
      answered by 14 % and 25 % participants, respectively. A total of 19 - 38 % of
      participants did not answer those statements correctly, including appropriate
      behaviour on the ski slope (overtaking, priority, stopping, and adapting speed).
      Significant differences in safety knowledge were found with regard to the type of
      sport performed, gender, age classes, skill level, frequency of winter sport
      participation per season, and previous injury. Conclusion Safety knowledge in
      this study was significantly lower among snowboarders, females, the youngest age
      group, beginners, and persons without a previous injury.

PMID- 28746950
TI  - [Bayes' Theorem and Base Rate Error: On the Predictive Value of Risk Factors and
      Screening Tests].
AB  - Regularly, risk assessments or decisions are based on dichotomous characteristics
      or measures. For instance, critical high values in screening tests may indicate
      an enhanced risk of having a disease. The prevalence of a risk factor (e. g. high
      blood pressure, depression) may indicate the need of a medical treatment or the
      occurrence of a negative consequence (e. g. early retirement). In such situations
      risk assessments are typically based on conditional event rates or conditional
      event probabilities: What is the risk of having a disease under the condition of
      having a symptom, risk factor or a critical screening indication? The valid
      interpretation of conditional event rates poses a considerable challenge for
      practitioners as well as for rehabilitation patients. Typically, for rare events
      the risk of having a disease is considerably overestimated if a critical
      predictor prevails. The Bayes' theorem describes the decision related
      informations structure appropriately. It is shown, which informations have to be
      taken into account to ensure valid risk assessments. Using absolute frequencies
      instead of relative frequencies or proportions may prevent erroneous conclusions.
      Graphical displays of absolute frequencies by area diagrams or decision trees are
      recommended to ensure a better comprehensibility of risk information.

PMID- 28746949
TI  - [Dislocation of the PIP-Joint - Treatment of a common (ball)sports injury].
AB  - Background Fractures or fracture dislocations of the proximal interphalangeal
      joint often occur during sports or accidents. Dislocations of the PIP-joint are
      the most common ligamentary injuries of the hand. As this kind of injury is so
      frequent, hand surgeons and other physicians should be aware of the correct
      treatment. Objectives This paper summarises the most common injury patterns and
      the correct treatment of PIP-joint dislocations. Materials and Methods This paper
      reviews the current literature and describes the standardised treatment of PIP
      joint dislocations. Results What is most important is that reposition is
      anatomically correct, and this should be controlled by X-ray examination.
      Depending on the instability and possible combination with other injuries (e. g.
      injury to the palmar plate), early functional physiotherapy of the joint or a
      short immobilisation period is indicated. Conclusions Early functional treatment
      of the injured PIP-joint, initially using buddy taping, is important to restore
      PIP-joint movement and function. Depending on the injury, joint immobilisation
      using a K-wire may be indicated. Detailed informed consent is necessary to
      explain to the patient the severity of the injury and possible complications,
      such as chronic functional disorders or development of arthrosis.

PMID- 28746951
TI  - [Exercise Therapy in German Medical Rehabilitation - an Analysis based on
      Quantitative Routine Data].
AB  - AIM OF THIS STUDY: This study describes the quantitative importance of exercise
      therapy in German medical rehabilitation based on 2014 routine data of the German
      Pension Insurance. It also shows changes in comparison with data from 2007.
      METHODS: Data from 710012 rehabilitation discharge letters comprising 83677802
      treatments from central indications in medical rehabilitation were analysed
      descriptively. RESULTS: Overall 35.4% of treatments could be classified as
      exercise therapy. Total and relative duration, percentage of individual treatment
      and kind of exercise treatment varied between indications in 2007 as well as in
      2014. There were also differences between sexes, age groups and settings.
      CONCLUSION: During the period examined the high importance of exercise therapy in
      German medical rehabilitation has increased. The results point at a meaningful
      concept behind the composition of exercise therapy taking indications and disease
      related factors into account.

PMID- 28746952
TI  - [Return to Work after Disk Surgery - Influenced by Rehabilitation?]
AB  - OBJECTIVE: The aim of this study was a comparison of treatment results in the
      year after disk surgery between the following treatment groups: rehabilitation
      immediately after discharge from hospital, rehabilitation with a transition time
      (at home) up to twenty days after rehabilitation or no rehabilitation. METHODS:
      On basis of claims data from a statutory health insurance and the German Federal
      Pension Fund the comparison of treatment results was performed. Therefore,
      duration of disability, return to work and early retirement are considered as
      treatment results and are analyzed using general linear models (GLM). Furthermore
      utilization of occupational rehabilitation was compared between the treatment
      groups with logistic regression. RESULTS: Rehabilitants showed a lower risk of
      unemployment. Moreover, rehabilitants utilize more often occupational
      rehabilitation. Both rehabilitation treatment groups had a higher duration of
      disability (including duration of rehabilitation) in the first quarter after
      surgery. Afterwards the duration of disability decreased faster. Risk of early
      retirement was higher in patients that started rehabilitation immediately.
      CONCLUSION: Rehabilitants tend to have better treatment results in the year
      following disc surgery.

PMID- 28746953
TI  - [Outpatient vs. Inpatient Rehabilitation: Findings of a Propensity Score Matched
      Analysis].
AB  - Objective Comparison of outpatient and inpatient rehabilitation concerning
      disability pensions and further work participation outcomes Methods We included
      18-60 years old patients who completed an inpatient or outpatient rehabilitation
      program due to musculoskeletal disorders during the first half of 2007.
      Outpatient and inpatient patients were matched by propensity scores.
      Administrative data were analysed. Results Our primary analyses compared 4752
      outpatient and 7435 inpatient patients. The absolute risks of a disability
      pension were 3.8% and 5.2% in favour of outpatient participants (RR=0.73; 95% CI:
      0.62 to 0.87). The duration of unemployment and sickness benefits were marginally
      lower for outpatient patients. Conclusions Outpatient rehabilitation achieved
      slightly better outcomes. The benefit of outpatient rehabilitation was strongest
      in patients with more severe restrictions of participation. The study explores
      how using administrative data may enable evaluative rehabilitation service
      research.

PMID- 28746954
TI  - [Trends of Tobacco and Alcohol Consumption over 65 Years in Germany].
AB  - AIM: No estimation was available for tobacco and for alcohol consumption in
      Germany based on sales data that were provided for public use and suited for time
      trend analysis. OBJECTIVES: To estimate trends of tobacco and alcohol consumption
      rates for the years 1950-2014. METHODS: Data on tobacco and alcohol consumption
      in the nation were retrieved from reports made by producers of beer, wine, or
      spirits to the Federal Statistics Office of Germany. Time trends over the 65
      years were calculated using the program Joinpoint. RESULTS: Tobacco consumption
      rose from 1950 to 1972. Thereafter it decreased, mostly by 1.2-6.9 percentage
      points per year. Alcohol consumption rose until the year 1974 and decreased
      thereafter by 1.0 percentage points annually until the end of the time period
      under analysis in 2014. CONCLUSIONS: The findings may be explained, among others,
      by changes of social norms according to smoking and alcohol consumption after tax
      increases, nonsmoker and youth protection laws, and legislative measures against
      driving under the influence of alcohol. A steepening of the decrease in tobacco
      consumption occurred after laws including tax increases had come into effect.
      However, the tobacco and alcohol consumption levels were still high at the end of
      the observation period in 2014.

PMID- 28746955
TI  - [Strength and weaknesses of the German digital health economy].
AB  - There are high expectations from digitalization of health care, ehealth and
      telemedicine. Nevertheless, the diffusion of these services falls short of
      expectations. This study analyses the strength and weaknesses of the German
      digital health economy. Thereby, we specially focus on small and medium-sized
      enterprises (SME). The study is based on a literature review, interviews of
      experts and a workshop. The digital health economy is influenced by a
      heterogeneous environment with both promotive and obstructive factors. One of the
      largest weaknesses results from a lack of business models. There is a lack of
      possibilities of reimbursement by the Statutory Health Insurance (SHI). In
      addition, private users only have a small willingness to pay for digital
      services. The large number of regulations makes the implementation even harder,
      especially for SMEs. Thus, the current environment hampers fast diffusion of
      digital services in the German health care market.

PMID- 28746956
TI  - [Advance Directives in Family Practices: Results of a Survey of GP Patients on
      their Care Situation].
AB  - Background Advance directives (AD) are an important tool for documentation of
      patients' wishes and are therefore recommended to the elderly as well as patients
      with chronic diseases. However, there is no standardized procedure in Germany and
      no guideline for counseling patients who wish to write an AD with or without
      health care proxy. The aim of this study was to evaluate the care situation
      concerning the ADs and the role of the primary care physician in drafting the
      document Method We conducted semi-structured interviews with patients in primary
      care in North Rhine-Westphalia using a cross-sectional study design. Result Most
      of the 154 patients who were interviewed (average age: 58 years; 52% female)
      suffered from chronic diseases (79%), and about one-third (32%) already had an
      AD. Fear of "loss of autonomy" was the main reason for preparing an AD. Patients
      without AD were generally not opposed to the concept and named procrastination
      (43%) as the main reason for not having prepared one. The chance for preparing an
      AD increased by the factor 1.08 per life-year (Odds ratio (OR): 1.08; CI: 1.04
      1.11). Patients with AD mostly got advice via the internet (22%), their primary
      care physicians (12%) and relatives (12%). Most patients were satisfied with
      their AD. Conclusion The majority of primary care patients do not make use of
      ADs. The primary care physicians play an important role in counseling and should
      motivate patients to complete ADs. Here, the establishment of quality standards
      would be desirable in the future.

PMID- 28746957
TI  - [Need for Information about Medical Rehabilitation of Persons with German Pension
      Insurance: a Written Survey].
AB  - AIM: In order to acquire target group-specific information on rehabilitation for
      members of the German pension insurance, they were asked about their ideas about
      medical rehabilitation and desired information regarding subjects and kind of
      information transfer. METHOD: The core of the project was a written survey of
      members of the German pension insurance. N=600 insured people were invited to
      participate in the study. The questionnaire was developed in a qualitative pre
      study. RESULTS: N=196 questionnaires were evaluated. Recovery of working ability
      was mentioned by most persons as the aim of medical rehabilitation. The most
      common idea regarding indication for rehabilitation was a specific operation.
      Physiotherapy was most often considered as therapy during medical rehabilitation.
      Information about formal steps, realistic aims and rehabilitation clinics were
      important. A conversation with their physician, written information material and
      a website were the preferred information pathways. Two-thirds of participants
      thought that information about medical rehabilitation was important even though
      they had no rehabilitation indication at the time of survey. CONCLUSION: The
      identified target-related information needs can be considered in a need-oriented
      development of information material. These can contribute to an informed decision
      for members of the German pension insurance for or against medical rehabilitation
      or an application for rehabilitation. Moreover, patient-oriented information can
      contribute to more successful rehabilitation participation, higher satisfaction
      with and a better rating of medical rehabilitation.

PMID- 28746958
TI  - Video Comment on Geir Hoff et al.

PMID- 28746959
TI  - Video Comment on Jiun-Nong Lin et al.

PMID- 28746960
TI  - Video Comment on Adriane Lesne et al.

PMID- 28746962
TI  - Video Comment on Kenichi Takeda et al.

PMID- 28746961
TI  - Video Comment on Osamu Goto et al.

PMID- 28746963
TI  - "Seek and you shall find" The Bible, Matthew 7:7.

PMID- 28746964
TI  - Infection following lower gastrointestinal endoscopy: silent risk or non-event?

PMID- 28746965
TI  - Computer-aided diagnosis: further eliminating the human factor in endoscopy?

PMID- 28746968
TI  - [French comment on article Submucosal fibrosis in achalasia patients is a rare
      cause of aborted peroral endoscopic myotomy procedures].

PMID- 28746969
TI  - [French comment on article Patient-reported adverse events after colonoscopy in
      Norway].

PMID- 28746970
TI  - [French comment on article Risk of infection following colonoscopy and
      sigmoidoscopy in symptomatic patients].

PMID- 28746971
TI  - [French comment on article Adenoma detection with blue-water infusion
      colonoscopy: a randomized trial].

PMID- 28746972
TI  - [French comment on article Cold polypectomy for duodenal adenomas: a prospective
      clinical trial].

PMID- 28746973
TI  - Prenatal Maternal Hyperoxygenation Testing and Implications for Critical Care
      Delivery Planning among Fetuses with Congenital Heart Disease: Early Experience.
AB  - BACKGROUND:  Maternal hyperoxygenation (MH) during fetal ultrasound can
      characterize fetal pulmonary vasoreactivity (PVr) and its associations with
      postnatal physiology. OBJECTIVE:  We explored MH testing to facilitate perinatal
      risk stratification for fetuses with congenital heart disease (CHD). METHODS:  MH
      was performed in 12 fetuses: 2 with Ebstein anomaly, 2 with total anomalous
      pulmonary venous connection (TAPVC), 4 with hypoplastic left heart syndrome
      (HLHS) with (a) restrictive atrial septum (RAS) or (b) intact atrial septum (IAS)
      with decompressing vertical vein (VV), and 4 with D-loop transposition of the
      great arteries (TGA). PVr and physiologic and anatomic changes with MH and
      outcomes were recorded. RESULTS:  Among Ebstein fetuses, pulmonary blood flow
      with MH mirrored postnatal findings. Among TAPVC fetuses, MH VV gradients
      correlated with postnatal gradients. One HLHS/IAS/VV fetus had no PVr and
      decreased pulmonary vein forward to reverse velocity time integral ratio with MH.
      Shortly after delivery, the infant experienced severe low cardiac output and
      required urgent atrial septoplasty. The remaining HLHS fetuses had PVr and
      underwent routine Stage 1 Norwood. Among TGA fetuses, septum primum position,
      foramen ovale flow, and the presence or absence of PVr with MH reflected
      postnatal findings. CONCLUSION:  MH may help identify fetuses with CHD at risk
      for perinatal compromise. Additional study may yield insights into fetal PVr and
      elucidate predictors of perinatal outcomes.

PMID- 28746974
TI  - mRNPs meet stress granules.
AB  - Stress granules are cytoplasmic structures that form in response to a variety of
      cellular stresses. They contain mRNAs and many proteins including numerous types
      of RNA-binding proteins, and have been studied in connection to major cellular
      events such as protein synthesis as well as disease. Despite the well-known fact
      that stress granules encapsulate mRNPs (mRNA-protein complexes), much of the
      research has naturally focused on the protein components of stress granules. The
      specific details of mRNP entry into and exit from stress granules and the
      functional reasons for these dynamics are not fully understood. Here, we review
      studies that have concentrated on the aspects of mRNP accumulation in stress
      granules and produced quantitative data concerning mRNP/stress granule
      interactions.

PMID- 28746975
TI  - Breeding habitat selection across spatial scales: is grass always greener on the
      other side?
AB  - Habitat selection theory predicts that natural selection should favor mechanisms
      allowing individuals to choose habitats associated with the highest fitness
      prospects. However, identifying sources of information on habitat quality that
      individuals use to choose their breeding habitat has proved to be difficult. It
      has also proven difficult to identify dispersal costs that prevent individuals
      from joining the highest-quality sites. A synthesis that integrates dispersal
      costs and habitat selection mechanisms across space has remained elusive. Because
      costs of dispersal are generally distance-dependent, we suggest that a habitat
      selection strategy of sequential proximity search (SPS) can be favored by natural
      selection. This strategy requires that animals make decisions at multiple scales:
      whether to stay or leave the previous breeding site, depending on reproductive
      success; then, if dispersal is chosen, use information on neighborhood habitat
      quality to decide whether to stay in the neighborhood or leave, expanding the
      search area until the nearest suitable site is chosen. SPS minimizes distance
      dependent dispersal costs while maximizing benefits of gaining a better habitat.
      We found evidence of breeding dispersal behavior consistent with this strategy in
      a kittiwake population stratified into a spatial hierarchy from colonies to nest
      sites. We used a mixed sequential regression model to study dispersal decisions,
      indexed by breeding dispersal movement, of 2,558 individuals over 32 yr. Scale
      dependent dispersal propensities of kittiwakes varied according to breeding
      status, breeding experience, sex and individual identity. We suggest that
      distance-dependent dispersal costs result from strong competition among
      kittiwakes for nest sites. Individual decisions regarding dispersal (whether to
      leave or not, and where to go) depend on nesting habitat quality as well as the
      competitive ability required to keep territory ownership in a previous site, or
      to acquire a new site; this ability varies according to distance between sites
      and individual characteristics. Additional studies are needed to establish the
      generality of SPS in habitat selection.

PMID- 28746976
TI  - Glucose-targeted therapy for subjects with type 2 diabetes mellitus: primum non
      nocere.

PMID- 28746977
TI  - Intratumoral stromal morphometry predicts disease recurrence but not response to
      5-fluorouracil-results from the QUASAR trial of colorectal cancer.
AB  - AIMS: The biological importance of tumour-associated stroma is becoming
      increasingly apparent, but its clinical utility remains ill-defined. For stage
      II/Dukes B colorectal cancer (CRC), clinical biomarkers are urgently required to
      direct therapeutic options. We report here prognostic/predictive analyses, and
      molecular associations, of stromal morphometric quantification in the Quick and
      Simple and Reliable (QUASAR) trial of CRC. METHODS AND RESULTS: Relative
      proportions of tumour epithelium (PoT) or stroma (PoS) were morphometrically
      quantified on digitised haematoxylin and eosin (H&E) sections derived from 1800
      patients enrolled in QUASAR, which randomised 3239 (91% stage II) CRC patients
      between adjuvant fluorouracil/folinic acid (FUFA) chemotherapy and observation.
      The prognostic and predictive values of PoT/PoS measurements were determined by
      the use of stratified log-rank analyses. A high proportion of tumour stroma
      (>=50%) was associated with an increased recurrence risk: 31.3% (143/457)
      recurrence for >=50% versus 21.9% (294/1343) for <50% [rate ratio (RR) 1.62; 95%
      confidence interval (CI) 1.30-2.02; P < 0.0001]. Of patients with stromal
      proportions of >=65%, 40% (46/115) had recurrent disease within 10 years. The
      adverse prognostic effect of a high stromal proportion was independent of
      established prognostic variables, and was maintained in stage II/Dukes B patients
      (RR 1.62; 95% CI 1.26-2.08; P = 0.0002). KRAS mutation in the presence of a high
      stromal proportion augmented recurrence risk (RR 2.93; 95% CI 1.87-4.59; P =
      0.0005). Stromal morphometry did not predict response to FUFA chemotherapy.
      CONCLUSIONS: Simple digital morphometry applied to a single representative H&E
      section identifies CRC patients with a >50% higher risk of disease recurrence.
      This technique can reliably partition patients into subpopulations with different
      risks of tumour recurrence in a simple and cost-effective manner. Further
      prospective validation is warranted.

PMID- 28746978
TI  - Digital image analysis of HER2 immunohistochemistry in gastric- and oesophageal
      adenocarcinoma: a validation study on biopsies and surgical specimens.
AB  - AIMS: To test the validity of diagnostics incorporating digital image analysis
      (DIA) for human epidermal growth factor 2 (HER2) immunohistochemistry (IHC) in
      gastro-oesophageal adenocarcinomas, as an alternative to current standard
      diagnostics using manual scoring. METHODS AND RESULTS: We included 319
      consecutive gastro-oesophageal adenocarcinomas (232 biopsies and 87 surgical
      specimens). DIA was applied to determine HER2 IHC classification, using both
      standard breast cancer (BC) and modified gastro-oesophageal cancer (GEC) cut
      offs. Consensus manual scores were established by four independent observers.
      Chromogenic in-situ hybridization (CISH) was performed on all 2+ cases by manual
      scoring, DIA or both. HER2 status was considered positive in 3+ and CISH-positive
      2+ cases. Overall agreement between DIA and consensus manual scores was 76.5%
      (weighted kappa = 0.66, BC cut-offs) and 85.6% (weighted kappa = 0.80, GEC cut
      offs). Agreement was similar for biopsies and surgical specimens. All
      disagreement occurred in the manual IHC equivocal cases. DIA resulted in a
      reduction of 2+ cases: 75.8% with BC cut-offs and 46.5% with GEC cut-offs. HER2
      status was positive in 48 cases (15%) with standard diagnostics and DIA using GEC
      cut-offs, and 46 cases (14.4%) using BC cut-offs (all with CISH in 2+ cases).
      Considering standard diagnostics as a reference, DIA showed 93.8% sensitivity and
      99.6% specificity (BC cut-offs) or 97.9% sensitivity and 99.6% specificity (GEC
      cut-offs). CONCLUSIONS: DIA is a reliable and feasible alternative to manual HER2
      IHC scoring in gastro-oesophageal adenocarcinoma, both in biopsies and surgical
      specimens, leading to a reduction of 2+ cases for which subsequent ISH testing is
      required.

PMID- 28746979
TI  - Feasibility of a new model for early detection of patients with multidrug
      resistant tuberculosis in a developed setting of eastern China.
AB  - OBJECTIVES: The poor detection rate of multidrug-resistant tuberculosis (MDR-TB)
      highlights the urgent need to explore new case finding model to improve the
      detection of MDR-TB in China. The aim of this study was to evaluate the
      feasibility of a new model that combines molecular diagnostics and sputum
      transportation for early detection of patients with MDR-TB in Zhejiang. METHODS:
      From May 2014 to January 2015, TB suspects were continuously enrolled at six
      county-level designated TB hospitals in Zhejiang. Each patient gave three sputum
      samples, which were submitted to laboratory for smear microscopy, solid culture
      and GeneXpert. The specimens from rifampin (RIF)-resistant cases detected by
      GeneXpert, and positive cultures were transported from county-level to prefecture
      level laboratories for line probe analysis (LPA) and drug susceptibility testing
      (DST). The performance and interval of MDR-TB detection of the new model were
      compared with those of conventional model. RESULTS: A total of 3151 sputum
      specimens were collected from TB suspects. The sensitivity of GeneXpert for
      detecting culture-positive cases was 92.7% (405/437), and its specificity was
      91.3% (2428/2659). Of 16 RIF-resistant cases detected by DST, GeneXpert could
      correctly identify 15 cases, yielding a sensitivity of 93.8% (15/16). The
      specificity of GeneXpert for detecting RIF susceptibility was 100.0% (383/383).
      The average interval to diagnosis of the conventional DST model was 56.5 days,
      ranging from 43 to 71 days, which was significantly longer than that of GeneXpert
      plus LPA (22.2 days, P < 0.01). CONCLUSION: Our data demonstrate that the
      combination of improved molecular TB tests and sputum transportation could
      significantly shorten the time required for detection of MDR-TB, which will bring
      benefits for preventing an epidemic of MDR-TB in this high-prevalence setting.

PMID- 28746980
TI  - Single-incision sling operations for urinary incontinence in women.
AB  - BACKGROUND: Urinary incontinence has been shown to affect up to 50% of women.
      Studies in the USA have shown that up to 80% of these women have an element of
      stress urinary incontinence. This imposes significant health and economic burden
      on society and the women affected. Colposuspension and now mid-urethral slings
      have been shown to be effective in treating patients with stress incontinence.
      However, associated adverse events include bladder and bowel injury, groin pain
      and haematoma formation. This has led to the development of third-generation
      single-incision slings, also referred to as mini-slings.It should be noted that
      TVT-Secur (Gynecare, Bridgewater, NJ, USA) is one type of single-incision sling;
      it has been withdrawn from the market because of poor results. However, it is one
      of the most widely studied single-incision slings and was used in several of the
      trials included in this review. Despite its withdrawal from clinical use, it was
      decided that data pertaining to this sling should be included in the first
      iteration of this review, so that level 1a data are available in the literature
      to confirm its lack of efficacy. OBJECTIVES: To assess the effectiveness of mini
      sling procedures in women with urodynamic clinical stress or mixed urinary
      incontinence in terms of improved continence status, quality of life or adverse
      events. SEARCH METHODS: We searched: Cochrane Incontinence Specialised Register
      (includes: CENTRAL, MEDLINE, MEDLINE In-Process) (searched 6 February 2013);
      ClinicalTrials.gov, WHO ICTRP (searched 20 September 2012); reference lists.
      SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in women
      with urodynamic stress incontinence, symptoms of stress incontinence or stress
      predominant mixed urinary incontinence, in which at least one trial arm involves
      one of the new single-incision slings. The definition of a single-incision sling
      is "a sling that does not involve either a retropubic or transobturator passage
      of the tape or trocar and involves only a single vaginal incision (i.e. no exit
      wounds in the groin or lower abdomen)." DATA COLLECTION AND ANALYSIS: Three
      review authors assessed the methodological quality of potentially eligible trials
      and independently extracted data from individual trials. MAIN RESULTS: We
      identified 31 trials involving 3290 women. Some methodological flaws were
      observed in some trials; a summary of these is given in the 'Risk of bias in
      included studies' section.No studies compared single-incision slings versus no
      treatment, conservative treatment, colposuspension, laparoscopic procedures or
      traditional sub-urethral slings. No data on the comparison of single-incision
      slings versus retropubic mid-urethral slings (top-down approach) were available,
      but the review authors believe this did not affect the overall comparison versus
      retropubic mid-urethral slings.Types of single-incision slings included in this
      review: TVT-Secur (Gynecare); MiniArc (American Medical Systems, Minnetonka,
      USA); Ajust (CR Bard Inc., Covington, USA); Needleless (Mayumana Healthcare,
      Lisse, The Netherlands); Ophira (Promedon, Cordoba, Argentina); Tissue Fixation
      System (TFS PTY Ltd, Sydney, Australia) and CureMesh (DMed Co. Inc., Seoul,
      Korea).Women were more likely to remain incontinent after surgery with single
      incision slings than with retropubic slings such as tension-free vaginal tape
      (TVTTM) (121/292, 41% vs 72/281, 26%; risk ratio (RR) 2.08, 95% confidence
      interval (CI) 1.04 to 4.14). Duration of the operation was slightly shorter for
      single-incision slings but with higher risk of de novo urgency (RR 2.39, 95% CI
      1.25 to 4.56). Four of five studies in the comparison included TVT-Secur as the
      single-incision sling.Single-incision slings resulted in higher incontinence
      rates compared with inside-out transobturator slings (30% vs 11%; RR 2.55, 95% CI
      1.93 to 3.36). The adverse event profile was significantly worse, specifically
      consisting of higher risks of vaginal mesh exposure (RR 3.75, 95% CI 1.42 to
      9.86), bladder/urethral erosion (RR 17.79, 95% CI 1.06 to 298.88) and operative
      blood loss (mean difference 18.79, 95% CI 3.70 to 33.88). Postoperative pain was
      less common with single-incision slings (RR 0.29, 95% CI 0.20 to 0.43), and rates
      of long-term pain or discomfort were marginally lower, but the clinical
      significance of these differences is questionable. Most of these findings were
      derived from the trials involving TVT-Secur: Excluding the other trials showed
      that high risk of incontinence was principally associated with use of this device
      (RR 2.65, 95% CI 1.98 to 3.54). It has been withdrawn from clinical use.Evidence
      was insufficient to reveal a difference in incontinence rates with other single
      incision slings compared with inside-out or outside-in transobturator slings.
      Duration of the operation was marginally shorter for single-incision slings
      compared with transobturator slings, but only by approximately two minutes and
      with significant heterogeneity in the comparison. Risks of postoperative and long
      term groin/thigh pain were slightly lower with single-incision slings, but
      overall evidence was insufficient to suggest a significant difference in the
      adverse event profile for single-incision slings compared with transobturator
      slings. Evidence was also insufficient to permit a meaningful sensitivity
      analysis of the other single-incision slings compared with transobturator slings,
      as all confidence intervals were wide. The only significant differences were
      observed in rates of postoperative and long-term pain, and in duration of the
      operation, which marginally favoured single-incision slings.Overall results show
      that TVT-Secur is considerably inferior to retropubic and inside-out
      transobturator slings, but additional evidence is required to allow any
      reasonable comparison of other single-incision slings versus transobturator
      slings.When one single-incision sling was compared with another, evidence was
      insufficient to suggest a significant difference between any of the slings in any
      of the comparisons made. AUTHORS' CONCLUSIONS: TVT-Secur is inferior to standard
      mid-urethral slings for the treatment of women with stress incontinence and has
      already been withdrawn from clinical use. Not enough evidence has been found on
      other single-incision slings compared with retropubic or transobturator slings to
      allow reliable comparisons. A brief economic commentary (BEC) identified two
      studies which reported no difference in clinical outcomes between single-incision
      slings and transobturator mid-urethral slings, but single-incision slings may be
      more cost-effective than transobturator mid-urethral slings based on one-year
      follow-up. Additional adequately powered and high-quality trials with longer-term
      follow-up are required. Trials should clearly describe the fixation mechanism of
      these single-incisions slings: It is apparent that, although clubbed together as
      a single group, a significant difference in fixation mechanisms may influence
      outcomes.

PMID- 28746981
TI  - Predicting life history parameters for all fishes worldwide.
AB  - Scientists and resource managers need to know life history parameters (e.g.,
      average mortality rate, individual growth rate, maximum length or mass, and
      timing of maturity) to understand and respond to risks to natural populations and
      ecosystems. For over 100 years, scientists have identified "life history
      invariants" (LHI) representing pairs of parameters whose ratio is theorized to be
      constant across species. LHI then promise to allow prediction of many parameters
      from field measurements of a few important traits. Using LHI in this way,
      however, neglects any residual patterns in parameters when making predictions. We
      therefore apply a multivariate model for eight variables (seven parameters and
      temperature) in over 32,000 fishes, and include taxonomic structure for residuals
      (with levels for class, order, family, genus, and species). We illustrate that
      this approach predicts variables probabilistically for taxa with many or few
      data. We then use this model to resolve three questions regarding life history
      parameters in fishes. Specifically we show that (1) on average there is a 1.24%
      decrease in the Brody growth coefficient for every 1% increase in maximum size;
      (2) the ratio of natural mortality rate and growth coefficient is not an LHI but
      instead varies systematically based on the timing of maturation, where movement
      along this life history axis is predictably correlated with species taxonomy; and
      (3) three variables must be known per species to precisely predict remaining life
      history variables. We distribute our predictive model as an R package, FishLife,
      to allow future life history predictions for fishes to be conditioned on taxonomy
      and life history data for fishes worldwide. This package also contains
      predictions (and predictive intervals) for mortality, maturity, size, and growth
      parameters for all described fishes.

PMID- 28746982
TI  - Myopia progression control lens reverses induced myopia in chicks.
AB  - PURPOSE: To determine whether lens induced myopia in chicks can be reversed or
      reduced by wearing myopia progression control lenses of the same nominal
      (central) power but different peripheral designs. METHODS: Newly hatched chicks
      wore -10D Conventional lenses unilaterally for 7 days. The myopic chicks were
      then randomly divided into three groups: one fitted with Type 1 myopia
      progression control lenses, the second with Type 2 myopia progression control
      lenses and the third continued to wear Conventional lenses for seven more days.
      All lenses had -10D central power, but Type 1 and Type 2 lenses had differing
      peripheral designs; +2.75D and +1.32D power rise at pupil edge, respectively.
      Axial length and refractive error were measured on Days 0, 7 and 14. Analyses
      were performed on the mean differences between treated and untreated eyes.
      RESULTS: Refractive error and axial length differences between treated and
      untreated eyes were insignificant on Day 0. On Day 7 treated eyes were longer
      (T1; 0.44 +/- 0.07 mm, T2; 0.27 +/- 0.06 mm, C; 0.40 +/- 0.06 mm) and more myopic
      (T1; -9.61 +/- 0.52D, T2; -9.57 +/- 0.61D, C; -9.50 +/- 0.58D) than untreated
      eyes with no significant differences between treatment groups. On Day 14 myopia
      was reversed (+2.91 +/- 1.08D), reduced (-3.83 +/- 0.94D) or insignificantly
      increased (-11.89 +/- 0.79D) in treated eyes of Type 1, Type 2 and Conventional
      treated chicks respectively. Relative changes in axial lengths (T1; -0.13 +/-
      0.09 mm, T2; 0.36 +/- 0.09 mm, C; 0.56 +/- 0.05 mm) were consistent with changes
      in refraction. Refractive error differences were significant for all group
      comparisons (p < 0.001). Type 1 length differences were significantly different
      from Conventional and Type 2 groups (p < 0.001). CONCLUSIONS: Myopia progression
      control lens designs can reverse lens-induced myopia in chicks. The effect is
      primarily due to axial length changes. Different lens designs produce different
      effects indicating that lens design is important in modifying refractive error.

PMID- 28746983
TI  - Sulfation of vitamin D3 -related compounds-identification and characterization of
      the responsible human cytosolic sulfotransferases.
AB  - While 25-hydroxyvitamin D3 3-O-sulfate is known to be present in circulation, how
      it is generated in the body remains unclear. This study aimed to investigate its
      sulfation in major human organs and to unveil the responsible cytosolic
      sulfotransferases (SULTs). Of the vitamin D3 -related compounds tested, 25
      hydroxyvitamin D3 and 7-dehydrocholesterol are preferentially sulfated by human
      organ cytosols. Among the 13 human SULTs, SULT2A1 shows sulfating activity toward
      all vitamin D3 -related compounds, whereas SULT1A1 and SULT2B1a/SULT2B1b show
      sulfating activity exclusively for, respectively, calcitriol and 7
      dehydrocholesterol. These findings suggest that the metabolic pathway leading to
      the formation of 25-hydroxyvitamin D3 3-O-sulfate may be mediated by the
      sulfation of 25-hydroxyvitamin D3 or by the conversion of 7-dehydrocholesterol-3
      O-sulfate in the skin.

PMID- 28746984
TI  - Identical TP53 mutations provide evidence that late-recurring tubo-ovarian high
      grade serous carcinomas do not represent new peritoneal primaries.

PMID- 28746985
TI  - West Nile Virus lineage-2 in Culex specimens from Iran.
AB  - OBJECTIVE: Screening of mosquitoes for viruses is an important forecasting tool
      for emerging and re-emerging arboviruses. Iran has been known to harbour
      medically important arboviruses such as West Nile virus (WNV) and dengue virus
      (DENV) based on seroepidemiological data. However, there are no data about the
      potential mosquito vectors for arboviruses in Iran. This study was performed to
      provide mosquito and arbovirus data from Iran. MATERIALS AND METHODS: A total of
      32 317 mosquitos were collected at 16 sites in five provinces of Iran in 2015 and
      2016. RT-PCR for detection of flaviviruses was performed. The PCR amplicons were
      sequenced, and 109 WNV sequences, including one obtained in this study, were used
      for phylogenetic analyses. RESULTS: The 32 317 mosquito specimens belonging to 25
      species were morphologically distinguished and distributed into 1222 pools. Culex
      pipiens s.l. comprised 56.429%. One mosquito pool (0.08%), containing 46 unfed
      Cx. pipiens pipiens form pipiens (Cpp) captured in August 2015, was positive for
      flavivirus RNA. Subsequent sequencing and phylogenetic analyses revealed that the
      detected Iranian WNV strain belongs to lineage 2 and clusters with a strain
      recently detected in humans. No flaviviruses other than WNV were detected in the
      mosquito pools. CONCLUSION: Cpp could be a vector for WNV in Iran. Our findings
      indicate recent circulation of WNV lineage-2 strain in Iran and provide a solid
      base for more targeted arbovirus surveillance programs.

PMID- 28746986
TI  - The histopathological classification, diagnosis and differential diagnosis of
      mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma
      peritonei.
AB  - The vermiform appendix is the primary site of several distinctive benign and
      malignant neoplasms. Some can produce the clinical syndrome of pseudomyxoma
      peritonei (PMP). A consensus on their terminology was reached by an international
      panel of pathologists and clinicians working under the auspices of the Peritoneal
      Surface Oncology Group International (PSOGI), and this review discusses the
      application of the PSOGI classification to routine reporting. We discuss
      diagnosis and differential diagnosis together with implications for patient
      management, covering low-grade appendiceal mucinous neoplasms, high-grade
      appendiceal mucinous neoplasms, serrated polyps, adenomas and adenocarcinomas. We
      do not cover goblet cell tumours or neuroendocrine neoplasms in this paper.

PMID- 28746987
TI  - Cytosolic redox components regulate protein homeostasis via additional
      localisation in the mitochondrial intermembrane space.
AB  - Oxidative protein folding is confined to the bacterial periplasm, endoplasmic
      reticulum and the mitochondrial intermembrane space. Maintaining a redox balance
      requires the presence of reductive pathways. The major thiol-reducing pathways
      engage the thioredoxin and the glutaredoxin systems which are involved in removal
      of oxidants, protein proofreading and folding. Alterations in redox balance
      likely affect the flux of these redox pathways and are related to ageing and
      diseases such as neurodegenerative disorders and cancer. Here, we first review
      the well-studied oxidative and reductive processes in the bacterial periplasm and
      the endoplasmic reticulum, and then discuss the less understood process in the
      mitochondrial intermembrane space, highlighting its importance for the proper
      function of the cell.

PMID- 28746988
TI  - The association between clinical outcome and CD8+ lymphocytic infiltration in
      advanced stages of colorectal cancer differs by latent virus infection in tumour
      tissue.
AB  - AIMS: In the near future, an immunoscore based on the quantification of
      lymphocytic populations can be expected as a fundamental supplement of colorectal
      cancer (CRC) classification. This study explored whether latent viral infection
      has an influence on prognostically relevant host immunity in CRC. METHODS AND
      RESULTS: CD8+ lymphocytic infiltration in three tumour compartments of 121 CRC
      was compared with clinical data and occurrence of latent infection with herpes
      simplex virus (HSV1, HSV2), cytomegalovirus (CMV), human papillomavirus (HPV16
      and HPV18) in the tumour tissue, which was determined by polymerase chain
      reaction (PCR). Intraepithelial CD8+ lymphocytic infiltration (IECD8+ ) showed a
      trend towards correlation with clinical stage (P = 0.073), significant
      differences between CRC with and without metastases (P = 0.001) and a significant
      correlation with overall survival (OS, P = 0.001). Each of these three clinical
      parameters showed a significant link to IECD8+ in the virus DNA-negative (P
      values: 0.001-0.036), but no significant differences in the virus DNA-positive
      subgroup, which is consistent with a moderating effect of virus DNA on these
      associations. A significant correlation of CD8+ infiltration in the invasive
      margin (IMCD8+ ) with OS (P = 0.016) was also moderated by virus DNA. CONCLUSION:
      Our data suggest a possible influence of latent viral infection on the
      association between clinical outcome and CD8+ lymphocytic infiltration in CRC
      tissue. After confirmation of these results by large cohort studies, a potential
      interaction between microbial pathogens and host immunity in CRC and its impact
      on prognostic immunoscores and/or new therapeutic strategies should be
      investigated further.

PMID- 28746989
TI  - Instability of the IncFII-Type Plasmid Carrying blaNDM-5 in a Klebsiella
      pneumoniae Isolate.
AB  - In this study, we characterized the blaNDM-5-bearing plasmid in a Klebsiella
      pneumoniae isolate that had lost the plasmid during serial passage. We determined
      the complete sequences of the plasmid pCC1410-2, which was extracted from a K.
      pneumoniae ST709 isolate collected at a Korean hospital from which two NDM-5
      producing K. pneumoniae isolates were subsequently isolated. As a result, the
      pCC1410-2 plasmid had a backbone structure that was similar to those of two
      plasmids previously reported from the same hospital, but lacked some antibiotic
      resistance genes (blaTEM-1, rmtB, mphR(A), mrx(A), and mph(A)). A 9-bp repeating
      unit encoding three amino acids (Gln-Gln-Pro) was inserted in TraD in pCC1410-2.
      Thus, the pCC1410-2 plasmid might be transferred from the previously identified
      carbapenem-resistant K. pneumoniae, but some delections and inversions might have
      occurred during the process. We compared the transfer frequency and stability of
      the plasmids. The relative frequency of conjugative transfer and stability in the
      host were significantly lower in pCC1410-2 than in previously reported blaNDM-5
      bearing plasmids in Korea. A low transfer frequency and instability in the host
      may cause underestimation of carbapenemase-producing Enterobacteriaceae in the
      clinical setting and in surveillance studies.

PMID- 28746990
TI  - Identification of a Gene Involved in the Negative Regulation of Pyomelanin
      Production in Ralstonia solanacearum.
AB  - Ralstonia solanacearum causes bacterial wilt in a wide variety of host plant
      species and produces a melanin-like blackish-brown pigment in stationary phase
      when grown in minimal medium supplemented with tyrosine. To study melanin
      production regulation in R. solanacearum, five mutants exhibiting overproduction
      of melanin-like pigments were selected from a transposon (Tn) insertion mutant
      library of R. solanacearum SL341. Most of the mutants, except one (SL341T), were
      not complemented by the original gene or overproduced melanins. SL341T showed Tn
      insertion in a gene containing a conserved domain of eukaryotic transcription
      factor. The gene was annotated as a hypothetical protein, given its weak
      similarity to any known proteins. Upon complementation with its original gene,
      the mutant strains reverted to their wild-type phenotype. SL341T produced 3-folds
      more melanin at 72 h post-incubation compared with wild-type SL341 when grown in
      minimal medium supplemented with tyrosine. The chemical analysis of SL341T
      cultural filtrate revealed the accumulation of a higher amount of homogentisate,
      a major precursor of pyomelanin, and a lower amount of dihydroxyphenylalanine, an
      intermediate of eumelanin, compared with SL341. The expression study showed a
      relatively higher expression of hppD (encoding hydroxyphenylpyruvate dioxygenase)
      and lower expression of hmgA (encoding homogentisate dioxygenase) and nagL
      (encoding maleylacetoacetate isomerase) in SL341T than in SL341. SL341 showed a
      significantly higher expression of tyrosinase gene compared with SL341T at 48 h
      post-incubation. These results indicated that R. solanacearum produced both
      pyomelanin and eumelanin, and the novel hypothetical protein is involved in the
      negative regulation of melanin production.

PMID- 28746991
TI  - Theory, Simulation, and Computation in Nanoscience and Nanotechnology.

PMID- 28746993
TI  - Aging impacts of low molecular weight organic acids (LMWOAs) on furfural
      production residue-derived biochars: Porosity, functional properties, and
      inorganic minerals.
AB  - The aging of biochar by low molecular weight organic acids (LMWOAs), which are
      typical root-derived exudates, is not well understood. Three LMWOAs (ethanoic,
      malic, and citric acids) were employed to investigate their aging impacts on the
      biochars from furfural production residues at 300-600 degrees C (BC300-600). The
      LMWOAs created abundant macropores in BC300, whereas they significantly increased
      the mesoporosity and surface area of BC600 by 13.5-27.0% and 44.6-61.5%,
      respectively. After LMWOA aging, the content of C and H of the biochars increased
      from 51.3-60.2% and 1.87-3.45% to 56.8-69.9% and 2.06-4.45%, respectively, but
      the O content decreased from 13.8-24.8% to 7.82-19.4% (except BC300). For carbon
      fraction in the biochars, the LMWOAs barely altered the bulk and surface
      functional properties during short-term aging. The LMWOAs facilitated the
      dissolution of minerals (e.g., K2Mg(PO3)4, AlPO4, and Pb2P2O7) and
      correspondingly promoted the release of not only plant nutrients (K+, Ca2+, Mg2+,
      Fe3+, PO43-, and SO42-) but also toxic metals (Al3+ and Pb2+). This research
      provided systematic insights on the responses of biochar properties to LMWOAs and
      presented direct evidence for acid activation of inorganic minerals in the
      biochars by LMWOAs, which could enhance the understanding of environmental
      behaviors of biochars in rhizosphere soils.

PMID- 28746994
TI  - Comparison between several reactors with Trametes versicolor immobilized on
      lignocellulosic support for the continuous treatments of hospital wastewater.
AB  - Hospital wastewater is a major source of pharmaceutically active compounds
      (PhACs), which are not all removed in conventional wastewater treatment plants.
      White rot fungi can degrade PhACs, but their application has been limited to non
      sterile conditions due to the competition with other microorganisms for growth.
      In this study, immobilization of Trametes versicolor on different lignocellulosic
      supports was studied as strategy to ensure fungal survival under continuous
      treatment conditions. A fluidized bed reactor and a trickling packed-bed reactor
      with T. versicolor immobilized on pallet wood were employed for the removal of
      ibuprofen, ketoprofen and naproxen. Best results were obtained with the trickling
      packed-bed reactor, which operated for 49days with high removal values in real
      hospital wastewater.

PMID- 28746995
TI  - Desorption of radioactive cesium by seawater from the suspended particles in
      river water.
AB  - In 2011, the accident at the Fukushima-Daiichi nuclear power plant dispersed
      radioactive cesium throughout the environment, contaminating the land, rivers,
      and sea. Suspended particles containing clay minerals are the transportation
      medium for radioactive cesium from rivers to the ocean because cesium is strongly
      adsorbed between the layers of clay minerals, forming inner sphere complexes. In
      this study, the adsorption and desorption behaviors of radioactive cesium from
      suspended clay particles in river water have been investigated. The radioactive
      cesium adsorption and desorption experiments were performed with two kinds of
      suspended particulate using a batch method with 137Cs tracers. In the cesium
      adsorption treatment performed before the desorption experiments, simulated river
      water having a total cesium concentration ([133+137Cs+]total) of 1.3 nM (10-9
      mol/L) was used. The desorption experiments were mainly conducted at a solid-to
      liquid ratio of 0.17 g/L. The desorption agents were natural seawater collected
      at 10 km north of the Fukushima-Daiichi nuclear power plant, artificial seawater,
      solutions of NaCl, KCl, NH4Cl, and 133CsCl, and ultrapure water. The desorption
      behavior, which depends on the preloaded cesium concentration in the suspended
      particles, was also investigated. Based on the cesium desorption experiments
      using suspended particles, which contained about 1000 ng/g loaded cesium, the
      order of cesium desorption ratios for each desorption agent was determined as 1 M
      NaCl (80%) > 470 mM NaCl (65%) > 1 M KCl (30%) ~ seawater (natural seawater and
      Daigo artificial seawater) > 1 M NH4Cl (20%) > 1 M 133CsCl (15%) ? ultrapure
      water (2%). Moreover, an interesting result was obtained: The desorption ratio in
      the 470 mM NaCl solution was much higher than that in seawater, even though the
      Na+ concentrations were identical. These results indicate that the cesium
      desorption mechanism is not a simple ion exchange reaction but is strongly
      related to structural changes in the clay minerals in the suspended particles.
      Hydrated Na+ ions expand the interlayer distance of the clay minerals, resulting
      in the facile desorption of cesium; in contrast, dehydrated K+ ions reduce the
      interlayer distance and inhibit the desorption of cesium. In conclusion, the
      desorption of cesium from the suspended particles is controlled by the presence
      of sodium and potassium ions and the preloaded cesium concentration in the
      suspended particles.

PMID- 28746996
TI  - The influence of bioavailable heavy metals and microbial parameters of soil on
      the metal accumulation in rice grain.
AB  - A field-based study was undertaken to analyze the effects of soil bioavailable
      heavy metals determined by a sequential extraction procedure, and soil microbial
      parameters on the heavy metal accumulation in rice grain. The results showed that
      Cd, Cr, Cu, Ni, Pb and Zn concentrations in rice grain decreases by 65.9%, 78.9%,
      32.6%, 80.5%, 61.0% and 15.7%, respectively in the sites 3 (far-away), compared
      with those in sites 1 (close-to). Redundancy analysis (RDA) indicated that soil
      catalase activity, the MBC/MBN ratio, along with bioavailable Cd, Cr and Ni could
      explain 68.9% of the total eigenvalue, indicating that these parameters have a
      great impact on the heavy metal accumulation in rice grain. The soil bioavailable
      heavy metals have a dominant impact on their accumulation in rice grain, with a
      variance contribution of 60.1%, while the MBC/MBN has a regulatory effect, with a
      variance contribution of 4.1%. Stepwise regression analysis showed that the
      MBC/MBN, urease and catalase activities are the key microbial parameters that
      affect the heavy metal accumulation in rice by influencing the soil bioavailable
      heavy metals or the translocation of heavy metals in rice. RDA showed an
      interactive effect between Cu, Pb and Zn in rice grain and the soil bioavailable
      Cd, Cr and Ni. The heavy metals in rice grain, with the exception of Pb, could be
      predicted by their respective soil bioavailable heavy metals. The results
      suggested that Pb accumulation in rice grain was mainly influenced by the multi
      metal interactive effects, and less affected by soil bioavailable Pb.

PMID- 28746997
TI  - Removal of bisphenol A by electrochemical carbon-nanotube filter: Influential
      factors and degradation pathway.
AB  - Bisphenol A is a chemical with hazardous health effects that is largely used in
      the manufacture of extensively used products including adhesives, plastics,
      powder paints, thermal paper and paper coatings, and epoxy resin, and is reported
      to exist in nature in an accumulative manner. In this study, both pristine and
      boron-doped multiwalled carbon nanotubes (MWNTs) were employed as filtration and
      electrochemical filtration materials, resulting in a significant removal of
      bisphenol A with identical performance for both MWNTs types. It was shown that
      the presence of salt is not critical for the greatest contaminant removal
      efficiency, likely due to the vital role of other electroactive species (e.g.
      reactive oxygen species). Near complete removal of 1 mg L-1 bisphenol A at 2 and
      3 V of applied DC potentials was achieved, indicating that the electrochemical
      filtration process is voltage dependent at both 2 and 3 V. Increasing the
      residence time by 7.4 fold (from 2.0 to 14.9 s) resulted in a significant removal
      of bisphenol A and its toxic byproducts, up to 424 min of electrochemical
      filtration time at 3 V of applied potential. Based on these results,
      electrochemical filtration using MWNTs is considered a promising technology for
      the removal of the accumulative bisphenol A and the reduction of its hazardous
      effects in waters.

PMID- 28746998
TI  - Bioaccumulation, distribution and elimination of chlordecone in the giant
      freshwater prawn Macrobrachium rosenbergii: Field and laboratory studies.
AB  - Chlordecone is a persistent organochlorine pesticide that has been widely used in
      Guadeloupe (French West Indies) to control the banana weevil Cosmopolites
      sordidus from 1972 to 1993. A few years after its introduction, widespread
      contamination of soils, rivers, wild animals and aquatic organisms was reported.
      Although high chlordecone concentrations have been reported in several crustacean
      species, its uptake, internal distribution, and elimination in aquatic species
      have never been described. This study aimed at investigating the accumulation and
      tissue distribution of chlordecone in the giant freshwater prawn Macrobrachium
      rosenbergii, using both laboratory (30 days exposure) and field (8 months
      exposure) approaches. In addition, depuration in chlordecone-free water was
      studied. Results showed that chlordecone bioconcentration in prawns was dose
      dependent and time-dependent. Moreover, females appeared to be less contaminated
      than males after 5 and 7 months of exposure, probably due to successive spawning
      leading in the elimination of chlordecone through the eggs. Chlordecone
      distribution in tissues of exposed prawns showed that cephalothorax organs,
      mainly represented by the hepatopancreas, was the most contaminated. Results also
      showed that chlordecone was accumulated in cuticle, up to levels of 40% of the
      chlordecone body burden, which could be considered as a depuration mechanism
      since chlordecone is eliminated with the exuviae during successive moults.
      Finally, this study underlined the similarity of results obtained in laboratory
      and field approaches, which highlights their complementarities in the chlordecone
      behaviour understanding in M. rosenbergii.

PMID- 28746999
TI  - Thermochemical emission and transformation of chlorinated paraffins in inert and
      oxidizing atmospheres.
AB  - Chlorinated paraffins (CPs) generally function as flame retardants and
      plasticizers in various materials. They are most likely to be processed by
      thermal processes during the entire life cycle. However, data on the formation
      and emission of CPs during thermal processes are still not fully understood. In
      this study, we simulated industrial thermal processes to investigate the emission
      of medium-chain chlorinated paraffins (MCCPs) and short-chain chlorinated
      paraffins (SCCPs) using commercial CP52 as the feedstock. We found that CP52
      decomposed very easily at 210-320  degrees C. The decomposition of CPs generated
      large quantities of MCCPs and SCCPs. These remained in the residue at low
      temperature (~200  degrees C) and were gradually released into the gas phase at
      higher temperatures. MCCPs and SCCPs were not detected in either the residue or
      the gas phase when the temperature exceeded 400  degrees C. However, considerable
      concentrations of aromatic and chlorinated aromatic hydrocarbons (Cl-PAHs) were
      identified in the gas phase, and they were formed as the amount of SCCPs and
      MCCPs decreased. Cl-PAHs were dominated by low-chlorinated chlorobenzenes,
      polychlorinated biphenyls, and polychlorinated naphthalenes. Oxygen promoted the
      release and decomposition of SCCPs in the gas phase. The results of the present
      study revealed the release of MCCPs and SCCPs and their synergistic emission with
      Cl-PAHs when CPs were subjected to heat. This work may also provide data for
      developing multiple techniques to control the emission of CPs and Cl-PAHs.

PMID- 28747000
TI  - Response of soil dissolved organic matter to microplastic addition in Chinese
      loess soil.
AB  - Plastic debris is accumulating in agricultural land due to the increased use of
      plastic mulches, which is causing serious environmental problems, especially for
      biochemical and physical properties of the soil. Dissolved organic matter (DOM)
      plays a central role in driving soil biogeochemistry, but little information is
      available on the effects of plastic residues, especially microplastic, on soil
      DOM. We conducted a soil-incubation experiment in a climate-controlled chamber
      with three levels of microplastic added to loess soil collected from the Loess
      Plateau in China: 0% (control, CK), 7% (M1) and 28% (M2) (w/w). We analysed the
      soil contents of dissolved organic carbon (DOC), dissolved organic nitrogen
      (DON), NH4+, NO3-, dissolved organic phosphorus (DOP), and PO43- and the
      activities of fluorescein diacetate hydrolase (FDAse) and phenol oxidase. The
      higher level of microplastic addition significantly increased the nutrient
      contents of the DOM solution. The lower level of addition had no significant
      effect on the DOM solution during the first seven days, but the rate of DOM
      decomposition decreased in M1 between days 7 and 30, which increased the nutrient
      contents. The microplastic facilitated the accumulation of high-molecular-weight
      humic-like material between days 7 and 30. The DOM solutions were mainly
      comprised of high-molecular-weight humic-like material in CK and M1 and of high
      molecular-weight humic-like material and tyrosine-like material in M2. The
      Microplastic stimulated the activities of both enzymes. Microplastic addition
      thus stimulated enzymatic activity, activated pools of organic C, N, and P, and
      was beneficial for the accumulation of dissolved organic C, N and P.

PMID- 28747001
TI  - Novel thiosemicarbazide derivatives with 4-nitrophenyl group as multi-target
      drugs: alpha-glucosidase inhibitors with antibacterial and antiproliferative
      activity.
AB  - A series of thiosemicarbazides with 4-nitrophenyl group was obtained in the
      reaction of carboxylic acid hydrazides with isothiocyanates. All compounds were
      checked for their antibacterial and antiproliferative activity. Our results have
      shown that derivatives 6-8 possessed antibacterial activity against S. aureus, S.
      epidermidis, S. mutans and S. sanguinis, moderate cytotoxicity and good
      therapeutic safety in vitro. Additionally, compounds 1 and 4 significantly
      inhibited A549, HepG2 and MCF-7 cell division. Moreover, PASS software indicated
      that newly obtained compounds are potential alpha-glucosidase inhibitors. This
      was confirmed by in vitro studies. To investigate the mode of interaction with
      the molecular target compounds were docked to glucose binding site of the enzyme
      and exhibited a similar binding mode as glucose.

PMID- 28747002
TI  - Managing metastatic bone pain: New perspectives, different solutions.
AB  - Bone metastases are the most frequent cause of cancer-induced bone pain (CIBP).
      Although palliative radiotherapy and pharmacotherapy conducted according to World
      Health Organization (WHO) analgesic ladder are the treatment of choice for CIBP
      reduction, these methods are not always successful, especially with regard to
      alleviation of incidental pain. Antiresorptive drugs (bisphosphonates) are able
      to inhibit bone destruction (loss), proliferation of cancer cells and
      angiogenesis, but their prolonged use may lead to a spectrum of adverse effects.
      In this paper, types of bone metastases, their complications, as well as
      diagnostic and therapeutic implications are presented. Moreover, the paper
      discusses presently used CIBP treatment methods and research directions for
      future methods, with special focus on bone metastases.

PMID- 28747003
TI  - Baicalein: A review of its anti-cancer effects and mechanisms in Hepatocellular
      Carcinoma.
AB  - Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) is a flavonoid
      compound derived from the roots of Scutellaria baicalensis. It has historically
      been used in anti-oxidant, anti-virus, anti-bacteria, anti-inflammatory and anti
      allergic therapies. Recently, baicalein has been found to possess anti-cancer
      activities via its effect on a variety of biological processes involving cell
      proliferation, metastasis, apoptosis and autophagy and so on. Hepatocellular
      carcinoma (HCC) is one of the most prevalent malignancies and high fatality rate
      worldwide. Noteworthy, treatment protocols of HCC include conventional resection
      and chemotherapy, all of which may result in enormous mortality rate. Therefore,
      there is extreme interest to find a relatively non-toxic medicine which may
      reduce side effects without compromising therapeutic efficacy. Many studies have
      showed that baicalein is one such potential candidate. In this review, we
      summarized the various anti-cancer effects of baicalein on HCC and their
      underlying molecular mechanisms based on in vitro and in vivo experimental
      evidences discovered so far. Taken together, baicalein may be developed as a
      potential, novel anticancer drug for HCC treatment.

PMID- 28747004
TI  - The stability and removal of water-dispersed CdSe/CdS core-shell quantum dots
      from water.
AB  - The increasingly wide use of semiconductor nanocrystals inevitably leads to their
      release into aquatic environment. The aggregation behaviors of 3
      mercaptopropionic acid-capped CdSe/CdS core-shell quantum dots (MPA-QDs) under
      various water chemistry conditions were examined and their removal using Fe3+ and
      Al3+ coagulants was evaluated. Cationic species rather than concentrations
      affected the stability of MPA-QDs. Adding 2 mM Ca2+ led to a much larger zeta
      potential decrease and particle size increase than adding 150 mM K+ at each
      tested solution pH. This indicated that complexation and depletion of surface
      bound carboxyl groups by divalent Ca2+ has a more pronounced effect than
      compression of the electrical double layer by high concentrations of monovalent
      K+. The presence of humic acid increased the stability of MPA-QDs, which might
      increase negative surface charging via overcoating or bind to the surface of MPA
      QDs. The nanoparticles exhibited similar aggregation kinetics patterns in tap
      water and seawater, but varying patterns in the lake water because of the co
      existence of 2.3 mM total of Ca2+ and Mg2+. MPA-QDs (5 mg L-1) were readily
      coagulated by 2.4 mM Al3+ or 1.2 mM Fe3+ in tap water. Al3+ and Fe3+ can bind
      with carboxyl groups of the surface capping ligands, neutralize the negative
      charges on the surface of MPA-QDs and decrease the electrostatic repulsion forces
      to induce MPA-QDs aggregation. In addition, MPA-QDs could be bound with and
      wrapped into the flocs of hydrolysis products of coagulants. The results reported
      here could help broaden our understanding of the impacts and remediation of water
      dispersed core-shell QD nanoparticles.

PMID- 28747005
TI  - Dermal penetration and resorption of beta-naphthylamine and N-phenyl-beta
      naphthylamine from lubricants in an ex vivo human skin model.
AB  - Dermal Penetration of aromatic amines (AA's), often suspected or known to be
      carcinogenic, can play an important role in the overall human exposure. However,
      information on penetration of certain AA's is poor and inconsistent. Penetration
      of the former lubricant additive N-phenyl-beta-naphthylamine (PBNA) and its
      contaminant beta-naphthylamine (BNA) a known carcinogen was investigated and the
      influence of formulation and co-application characterized. Percutaneous
      penetration of BNA and PBNA through freshly excised human skin (n = 8; 48 h) was
      investigated using an ex vivo diffusion cell model. Both AA's were applied in a
      technical-conform lubricant or dissolved in hexane. The amount of BNA and PBNA
      applied to skin was 0.52 and 259 MUg/0.64 cm2. The analytical determination of
      AA's was performed by GC-MS. Both, BNA and PBNA penetrated through human skin (38
      vs. 5% of applied dose). In contrast to BNA, the percutaneous penetration of PBNA
      continued beyond the end of exposure. Co-exposure of both AA's increased the
      intradermal uptake of BNA and PBNA (p < 0.05). Exposure in lubricant showed the
      least overall penetration (2.9 and 1.9% of applied dose). The results clearly
      reveal that dermal penetration of both AA's depends strongly on the mode of
      application. Co-application and formulation alters the penetration of the AA's.

PMID- 28747006
TI  - Biotoxic impact of heavy metals on growth, oxidative stress and morphological
      changes in root structure of wheat (Triticum aestivum L.) and stress alleviation
      by Pseudomonas aeruginosa strain CPSB1.
AB  - Rapid industrialization and uncontrolled metal discharge into environment is a
      global concern for crop production. Metal tolerant bacterium isolated from chilli
      rhizosphere was identified as Pseudomonas aeruginosa by 16S rDNA sequence
      analysis. Pseudomonas aeruginosa tolerated high concentrations of Cu (1400 MUg ml
      1), Cd (1000 MUg ml-1) and Cr (1000 MUg ml-1). Pseudomonas aeruginosa CPSB1
      produced multiple plant growth promoting biomolecules in the presence and absence
      of metals. Strain CPSB1 solubilized P at 400 MUg ml-1 of Cd, Cr and Cu. The
      strain was positive for indole-3-acetic acid (IAA), siderophores, hydrogen
      cyanide (HCN), ammonia (NH3) and 1-aminocyclopropane-1-carboxylate (ACC)
      deaminase when grown with/without metals. The phytotoxic effects on wheat
      increased with increasing Cd, Cr and Cu rates. The P. aeruginosa CPSB1 inoculated
      wheat in contrast had better growth and yields under Cu, Cd and Cr stress. The
      root dry biomass of inoculated plants was enhanced by 44, 28 and 48% at 2007 mg
      Cu kg-1, 36 mg Cd kg-1 and 204 mg Cr kg-1, respectively. The bioinoculant
      enhanced number of spikes, grain and straw yields by 25, 17 and 12%,
      respectively. Pseudomonas aeruginosa CPSB1 significantly declined the levels of
      catalase (CAT), glutathione reductase (GR) and superoxide dismutase SOD), proline
      and malondialdehyde (MDA), and reduced metal uptake by wheat. The study
      demonstrated that P. aeruginosa CPSB1 possessed plant growth promoting
      potentials, showed metal tolerance capability and had ability to counteract
      deleterious metal impacts. Due to these, P. aeruginosa CPSB1 could be used as
      bioinoculant for enhancing wheat production even in metal contaminated soils.

PMID- 28747007
TI  - Ozone pretreatment of process waste water generated in course of fluoroquinolone
      production.
AB  - During production of active pharmaceutical ingredients, process waste water is
      generated at several stages of manufacturing. Whenever possible, the resulting
      waste water will be processed by conventional waste water treatment plants.
      Currently, incineration of the process waste water is the method to eliminate
      compounds with high biological activity. Thus, ozone treatment followed by
      biological waste water treatment was tested as an alternative method. Two
      prominent representatives of the large group of fluoroquinolone antibiotics
      (ciprofloxacin and moxifloxacin) were investigated, focussing on waste water of
      the bulk production. Elimination of the target compounds and generation of their
      main transformation products were determined by liquid chromatography - high
      resolution mass spectrometry (LC-HRMS). The obtained results demonstrated, that
      the concentration of moxifloxacin and its metabolites can be effectively reduced
      (>99.7%) prior entering the receiving water. On the contrary, the concentration
      of ciprofloxacin and its metabolites remained too high for safe discharge,
      necessitating application of prolonged ozonation for its further degradation. The
      required ozonation time can be estimated based on the determined kinetics. To
      assure a low biological activity the ecotoxicity of the ozonated waste water was
      investigated using three trophic levels. By means of multiple-stage mass
      spectrometry (MSn) experiments several new transformation products of the
      fluoroquinolones were identified. Thus, previously published proposed structures
      could be corrected or confirmed.

PMID- 28747008
TI  - Enhanced robustness in acetone-butanol-ethanol fermentation with engineered
      Clostridium beijerinckii overexpressing adhE2 and ctfAB.
AB  - Clostridium beijerinckii CC101 was engineered to overexpress aldehyde/alcohol
      dehydrogenase (adhE2) and CoA-transferase (ctfAB). Solvent production and acid
      assimilation were compared between the parental and engineered strains expressing
      only adhE2 (CC101-SV4) and expressing adhE2, ald and ctfAB (CC101-SV6). CC101-SV4
      showed an early butanol production from glucose but stopped pre-maturely at a low
      butanol concentration of ~6g/L. Compared to CC101, CC101-SV6 produced more
      butanol (~12g/L) from glucose and was able to re-assimilate more acids, which
      prevented "acid crash" and increased butanol production, under all conditions
      studied. CC101-SV6 also showed better ability in using glucose and xylose present
      in sugarcane bagasse hydrolysate, and produced 9.4g/L solvents (acetone, butanol
      and ethanol) compared to only 2.6g/L by CC101, confirming its robustness and
      better tolerance to hydrolysate inhibitors. The engineered strain of C.
      beijerinckii overexpressing adhE2 and ctfAB should have good potential for
      producing butanol from lignocellulosic biomass hydrolysates.

PMID- 28747009
TI  - Pilot scale repeated fed-batch fermentation processes of the wine yeast Dekkera
      bruxellensis for mass production of resveratrol from Polygonum cuspidatum.
AB  - Resveratrol has long been used as an ingredient in functional foods. Currently,
      Polygonum cuspidatum extract is the greatest natural source for resveratrol
      because of high concentrations of glycosidic-linked resveratrol. Thus, developing
      a cost-effective procedure to hydrolyze glucoside could substantially enhance
      resveratrol production from P. cuspidatum. This study selected Dekkera
      bruxellensis from several microorganisms based on its bioconversion and enzyme
      specific activities. We demonstrated that the cells could be reused at least nine
      times while maintaining an average of 180.67U/L beta-glucosidase activity. The
      average resveratrol bioconversion efficiency within five rounds of repeated usage
      was 108.77+/-0.88%. This process worked effectively when the volume was increased
      to 1200L, a volume at which approximately 35mgL-1h-1 resveratrol per round was
      produced. This repeated fed-batch bioconversion process for resveratrol
      production is comparable to enzyme or cell immobilization strategies in terms of
      reusing cycles, but without incurring additional costs for immobilization.

PMID- 28747010
TI  - Traditional knowledge to clinical trials: A review on therapeutic actions of
      Emblica officinalis.
AB  - Plants are the integral part of the traditional indigenous healthcare system and
      are becoming concrete source of new drug discovery, evident by the increasing
      numbers of modern drugs derived from the phytochemicals. Emblica officinalis
      Gaertn. or Phyllanthus emblica Linn (family Phyllanthaceae) has been explained
      extensively and well documented for its therapeutic efficacies in indigenous
      system of medicine, in India. Every part of this plant possesses high medicinal
      value but fruits are the most valuable part in folklore and therapeutic uses. The
      polyphenols found in E.officinalis, especially tannins and flavonoids are key
      responsible elements for major bioactivities. E.officinalis is one of the major
      component in various health tonics, also exerts synergistic effects in enhancing
      the medicinal efficacy. E.officinalis exhibits broad spectrum of pharmacological
      activities through various mode of actions including antioxidant, anticancer,
      immunomodulator, anti-inflammatory, cyto-protective properties etc. Medical
      practitioners across the globe also advocated its application in managing
      diabetes, dyslipidemia, obesity, several types of cancer, liver disorders,
      arthritis, gingivitis, wound healing etc. The present review analysed and
      summarized the pharmacological actions, experimental studies and clinical trials
      of E. officinalis with emphasis on its immuno-enhancer, antiinflammatory and
      anticancer activities and possible mechanism of actions to provide future
      directions in translating these findings clinically.

PMID- 28747011
TI  - Bioconversion of Scutellaria baicalensis extract can increase recovery of
      auditory function in a mouse model of noise-induced hearing loss.
AB  - In noise-induced hearing loss (NIHL), noise exposure damages cochlear sensory
      hair cells, which lack the capacity to regenerate. Following noise insult,
      intense metabolic activity occurs, resulting in a cochlear free radical
      imbalance. Oxidative stress and antioxidant enzyme alterations, including
      lipoxygenase upregulation, have been linked to chronic inflammation, which
      contributes to hearing impairment. We previously proposed Scutellaria baicalensis
      (SB) extract as an alternative therapeutic for preventing NIHL and attributed its
      pharmacological effects to baicalein. Although baicalein was most effective, its
      concentration in SB extract is much lower compared to baicalin. In this study, we
      performed enzymatic bioconversion using an Sumizyme (SM) enzyme to increase
      baicalein concentration in SB extract and consequently improve its therapeutic
      efficacy. HPLC analysis revealed that baicalein concentration in SB extract after
      bioconversion (BSB) was significantly increased. Moreover, BSB-treated mice
      exhibited significantly improved auditory function compared with control mice and
      tended to have improved auditory function compared with SB-treated mice. We also
      demonstrated that BSB effectively stimulates hair cell regeneration compared to
      SB that did not achieve the same effect in a zebrafish model. Finally, when
      compared the abilities of SB and BSB to inhibit lipoxygenase (LOX), BSB showed a
      greater efficacy. Cumulatively, our data suggest that BSB exhibits improved
      pharmacological properties for treating NIHL compared with SB.

PMID- 28747012
TI  - Immunohistochemical and biochemical alterations following administration of
      proanthocyanidin extract in rats hepatocellular carcinoma.
AB  - Grape seed proanthocyanidin extract (GSPE) is known to be effective on broad
      spectrum of biological pathways in living organisms including oxidative stress.
      The present study aimed to investigate the effects of proanthocyanidin on
      preneoplastic lesions and liver cancer induced in rats by Diethylnitrosamine
      (DEN). 7-8 Week old male Sprague Dawley (S.D.) rats were divided into six groups:
      The 1st group received no treatment and were -ve controls, the 2nd were treated
      with a single dose of DEN 200mg/kg intraperitoneally (i.p.) and served as +ve
      control group. The 3rd and 4th groups were injected with the same dose of DEN as
      in group 2 and then post treated with 300 or 150mg/kg/b.wt./day GSPE by
      intrgastroluminal gavage (i.g.) respectively until the end after the 22 weeks.
      Groups 5 and 6 were treated with the same doses of GSPE as in groups 3 and 4
      respectively without DEN administration. The results showed that the
      immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling indexes
      (PCNA LI%) were significantly inhibited in liver tissues and tumors by both
      treatments of GSPE. Furthermore, treatment with GSPE has modified the liver
      tissue oxidative stress markers levels of SOD, CAT, GSH, GST, GPx, GR and MDA
      changed by DEN. In conclusion, GSPE has a sufficient therapeutic effect against
      liver carcinogenesis through their free radical scavenging, inhibition of
      cellular proliferation.

PMID- 28747013
TI  - Estrogen can restore Tamoxifen sensitivity in breast cancer cells amidst the
      complex network of resistance.
AB  - Breast cancer-related deaths have been on the decline ever since the application
      of systemic therapies. Chiefly, endocrine therapy, such as Tamoxifen, enhances
      the survival of estrogen receptor (ER)-positive patients. More than a decade has
      passed since the introduction of Tamoxifen, however, drug resistance,
      particularly to Tamoxifen, still remains a major challenge. It has been shown
      that not only does chronic Tamoxifen exposures induce resistance, but estrogen
      deprivation can as well. There are two Tamoxifen resistant cell lines, long term
      estrogen deprived (LTED) cells and cells that have acquired resistance due to
      long-term exposure to Tamoxifen (Tam-R). Despite having similar cytosolic
      pathways over-activated in Tam-R and LTED-R cells during the development of
      resistance, the administration of receptor tyrosine kinases (RTKs) inhibitors
      fail to restore Tamoxifen sensitivity in LTED-Rs. This alludes to existing
      differences in the underlying molecular mechanisms of resistance. Surprisingly,
      despite estrogen being recognized as a breast cancer stimulator; it has recently
      been introduced as an apoptotic inducer in unresponsive cells. Furthermore, the
      addition of estrogen to the media of LTED and Tam-R cells triggers cell death,
      perhaps is functioning as an anti-proliferative agent. In this review, we outline
      the molecular pathways potentially facilitating estrogen-induced apoptosis in
      resistant cells.

PMID- 28747014
TI  - MicroRNAs and adipocytokines: Promising biomarkers for pharmacological targets in
      diabetes mellitus and its complications.
AB  - Nowadays, diabetes mellitus (DM) along with its complications is considered as a
      fundamental problem in both developing and industrial countries, and is causing
      millions of people to suffer worldwide. Currently, diabetes mellitus is diagnosed
      traditionally or classically in the world by measuring fasting blood glucose and
      conducting oral glucose tolerance test. New alternatives are required for the
      treatment of diabetes mellitus, especially type 2 diabetes mellitus (T2DM), at
      its early levels due to the ineffective control of its development in patients.
      In recent years, by further identifying of molecular agents such as microRNAs
      (miRNAs), studies have focused on miRNAs in diabetes as well as in other
      diseases. These small non-coding RNA molecules have a significant role in the
      regulation of insulin gene expression and also, obesity problems. White adipose
      tissue, as an important tissue in obese subjects, is directly related to type 2
      diabetes and its complications via synthesis of adipokines. Prevention and
      treatment of obesity should be noted since childhood. Our aim in this review is
      to briefly provide a new glance at types of potential biomarkers, which can be
      used as pharmacological targets for prevention and treatment of prediabetic
      subjects, and patients with T2DM.

PMID- 28747015
TI  - Nardilysin is a promising biomarker for the early diagnosis of acute coronary
      syndrome.
AB  - BACKGROUND: Biomarkers for detection of transient myocardial ischemia in patients
      with unstable angina (UA) or for very early diagnosis of acute myocardial
      infarction (AMI) are not currently available. METHODS AND RESULTS: We performed
      two sequential screenings of autoantibodies elevated shortly after the onset of
      acute coronary syndrome (ACS), and focused on metalloendopeptidase nardilysin
      (NRDC) among 19 identified candidate antigens. In a retrospective analysis among
      93 ACS and 117 non-ACS patients, the serum level of NRDC was significantly
      increased in patients with ACS compared with that in patients with non-ACS
      (2073.5+/-189.8pg/ml versus 775.7+/-63.4pg/ml, P<0.0001). The area under the
      curve of NRDC for the diagnosis of ACS was 0.822 by the receiver operating
      characteristic curves analysis. In the time course analysis in 43 consecutive ACS
      patients (AMI: N=35 and UA: N=8), serum concentration of NRDC was significantly
      increased even in UA patients with a peak serum NRDC levels reached at admission
      both in AMI and UA patients. In a mouse model of AMI, we found an acute increase
      in serum NRDC and reduced NRDC expression in ischemic regions shortly after
      coronary artery ligation. NRDC expression was also reduced in infarcted regions
      in human autopsy samples from AMI patients. Moreover, the short treatment of
      primary culture of rat cardiomyocytes with H2O2 or A23187 induced NRDC secretion
      without cell toxicity. CONCLUSION: NRDC is a promising biomarker for the early
      detection of ACS, even in UA patients without elevation of necrosis markers.

PMID- 28747016
TI  - Unveiling the elephant in the room: The dilemma of patients managed medically
      after Non-ST-segment Elevation Acute Coronary Syndromes.

PMID- 28747017
TI  - Myocardial protection by remote ischemic preconditioning in elective PCI: Effect
      of ageing.

PMID- 28747018
TI  - Reply to letter to the Editor: "Myocardial protection by remote ischemic
      preconditioning in elective PCI: Effect of aging".

PMID- 28747019
TI  - Is microvascular obstruction independent predictor of the major adverse
      cardiovascular events in latecomers after ST-elevation myocardial infarction?

PMID- 28747020
TI  - Microvascular obstruction is an independent predictor of major adverse
      cardiovascular events in latecomers after ST-elevation myocardial infarction.

PMID- 28747021
TI  - Characteristics and outcomes of medically managed patients with non-ST-segment
      elevation acute coronary syndromes: Insights from the multinational EPICOR Asia
      study.
AB  - BACKGROUND: Many patients with non-ST-segment elevation acute coronary syndromes
      (NSTE-ACS) are medically managed without coronary revascularization. The reasons
      vary and may impact prognosis. METHODS: EPICOR Asia (NCT01361386) is a
      prospective study of hospital survivors post-ACS enrolled in 218 hospitals from 8
      countries/regions in Asia (06/2011-05/2012). All medically managed NSTE-ACS
      patients were classified into 3 groups: 1) no coronary angiography (CAG-); 2) non
      significant coronary artery disease (CAD) on angiogram (CAG+ CAD-); and 3)
      significant CAD (CAG+ CAD+). We compared baseline differences between patients
      medically managed and patients undergoing revascularization, and also between the
      medically managed groups. Adverse events were reported and compared up to 2years.
      RESULTS: Of 6163 NSTE-ACS patients, 2272 (37%) were medically managed, with 1339
      (59%), 254 (11%), and 679 (30%) in the CAG-, CAG+ CAD-, and CAG+ CAD+ groups,
      respectively. There were marked differences in the proportion of medically
      managed patients among the 8 countries/regions (13-81%). Medically managed
      patients had higher mortality at 2years compared with revascularization (8.7% vs.
      3.0%, p<0.001). Among medically managed patients, CAG- patients were older, more
      likely to have pre-existing cardiovascular disease, and had the highest 2-year
      mortality (10.5% vs. 4.3% [CAG+ CAD-] and 6.6% [CAG+ CAD+], p<0.001). Mortality
      differences persisted after adjusting for other patient risk factors.
      CONCLUSIONS: Medically managed NSTE-ACS patients are a heterogeneous group with
      different risk stratification and variable prognosis. Identification of reasons
      underlying different management strategies, and key factors adversely influencing
      long-term prognosis, may improve outcomes.

PMID- 28747022
TI  - Patient reported outcomes are associated with physical activity level in adults
      with congenital heart disease.
AB  - BACKGROUND: In general, adults with congenital heart disease (CHD) have impaired
      exercise capacity, and approximately 50% do not reach current recommendations on
      physical activity. Herein we analysed factors associated with physical activity
      level (PAL) in adults with CHD by using patient-reported outcomes (PRO). METHODS:
      Patients with CHD (n=471) were randomly selected from the national register on
      CHD and categorized according to complexity of lesions - simple (n=172, 39.1+/
      14.6years), moderate (n=212, 39+/-14.1years), and severe (n=87, 31.7+/
      10.7years). Participants completed a standardized questionnaire measuring PRO
      domains including PAL. Variables associated with PAL were tested in multivariate
      logistic regression. RESULTS: PAL was categorized into high (>=3 METs
      >=2.5h/week, n=192) and low (>=3 METs <2.5h/week, n=279). Patients with low PAL
      were older (42.6 vs. 35.8years, p<=0.001), had more prescribed medications (51%
      vs. 39%, p=0.009), more symptoms (25% vs. 16%, p=0.02) and comorbidity (45% vs.
      34% p=0.02). Patients with low PAL rated a lower quality of life (76.6 vs. 83.4,
      p<0.001), satisfaction with life (25.6 vs. 27.3, p=0.003), a lower Physical
      Component Summary score (PCS) (78.1 vs. 90.5, p<0.001) and Mental Component
      Summary score (MCS) (73.5 vs. 79.5, p<0.001). Complexity of heart lesion was not
      associated with PAL. The included PROs - separately tested in the model, together
      with age were associated with PAL. CONCLUSIONS: PCS and MCS are stronger
      associated with PAL than age and medical factors. The use of these PROs could
      therefore provide valuable information of benefit for individualized advice
      regarding physical activity to patients with CHD.

PMID- 28747023
TI  - Exercise in Adult with Congenital Heart Disease: Not a chimaera anymore.

PMID- 28747024
TI  - Clinical profile and outcomes in octogenarians with atrial fibrillation: A
      community-based study in a specific European health care area.
AB  - BACKGROUND: Age increases risk of stroke and bleeding. Clinical trial data have
      had relatively low proportions of elderly subjects. We sought to study a Spanish
      population of octogenarians with atrial fibrillation (AF) by combining different
      sources of electronic clinical records from an area where all medical centres
      utilized electronic health record systems. METHODS: Data was derived from the
      Galician Healthcare Service information system. RESULTS: From 383,000 subjects,
      AF was coded in 7990 (2.08%), 3640 (45.6%) of whom were >=80 and 4350 (54.4%)<80.
      All CHA2DS2-VASc's components were more prevalent in the elderly except for
      diabetes. Of those >=80, 2178 (59.8%) were women. Mean CHA2DS2-VASc was 4.2+/
      1.1. Distribution of CHA2DS2-VASc components varied between genders. 2600 (71.4%)
      were on oral anticoagulant (OA). During a median follow up of 696days (124.23),
      all-cause mortality was higher in >=80 (1011/3640 (27.8%) vs 350/4350 (8.05%)
      (p<0.001). There were differences in rate of thromboembolic (TE) and haemorrhagic
      events (2.3% vs 0.9%, p<0.01 and 2.5% vs 1.7%, p=0.01 respectively). In
      octogenarian, differences between genders were observed with regard to TE, but
      not in haemorrhagic or all-cause mortality rates. Age, heart failure, non
      valvular AF, dementia, and OA were independent predictors of all-cause mortality.
      In regard to TE, female gender, hypertension, previous TE and OA were independent
      predictive factors. CONCLUSIONS: Octogenarians with AF had very different
      characteristics and outcomes from their younger counterparts. These results also
      provide reassurance about the effectiveness of OA in preventing TE events and
      maintaining a reasonable haemorrhagic event rate in the extremely elderly.

PMID- 28747025
TI  - Platelet function and microparticle levels in atrial fibrillation: Changes during
      the acute episode.
AB  - BACKGROUND: Thrombotic risk constitutes a major complication of atrial
      fibrillation (AF). Platelets and microparticles (MPs) are important for
      hemostasis and thrombosis, however their participation during AF is not well
      known. The aim of this study was to characterize platelet function and MPs
      procoagulant and fibrinolytic activity in AF patients and to determine the
      effects of an acute-AF episode. METHODS: Blood was collected from paroxysmal (21)
      and persistent (16) AF patients referred for AF catheter ablation. Ten patients
      in sinus rhythm for 10days were induced in AF allowing comparisons of left atrium
      samples before and after induction. Platelet aggregation with ADP, TRAP,
      collagen, and ristocetin was studied. Platelet surface expression of PAR-1,
      alphaIIbbeta3, GPIb and P-selectin were evaluated by flow cytometry, and MPs
      associated procoagulant and fibrinolytic activity levels were determined by
      functional assays. RESULTS: A specific reduction in platelet aggregation to TRAP,
      activating the thrombin receptor PAR-1, was found in all AF patients. No
      differences in platelet receptor expression were found. Yet, after acute-induced
      AF, the platelet response was improved. Furthermore, a significant decrease of
      left atrium tissue factor-dependent procoagulant activity of MPs was observed.
      CONCLUSION: Acute episodes of AF results in a decrease in MPs-associated tissue
      factor activity, possibly corresponding to consumption, which in turn favors
      coagulation and the local production of thrombin. A decreased platelet basal
      aggregation to TRAP may result from PAR1 desensitization, whereas the improved
      response after an induced episode of AF suggests activation of coagulation and
      PAR1 re-sensitization.

PMID- 28747026
TI  - Inferior and anterior QRS fragmentation have different prognostic value in
      patients who received an implantable defibrillator in primary prevention of
      sudden cardiac death.
AB  - AIMS: QRS fragmentation (fQRS) has been proposed as a predictor of sudden cardiac
      death (SCD) and all-cause mortality in ischemic (ICM) and non-ischemic
      cardiomyopathy patients. However the value of fQRS in patients with a LVEF <35%
      is a matter of debate. METHODS: All consecutive patients with an indication for
      an ICD in primary prevention of SCD were included in a retrospective registry
      from 1996 until 2013. Twelve lead electrocardiograms before implant were analyzed
      for the presence of fQRS in different regions. Adjusted Cox regression analysis
      for first appropriate ICD shock (AS) and all-cause mortality was performed.
      RESULTS: In total 407 patients were included with a mean follow-up of 4.2+/-3.3y
      (age 60.6+/-11.9y, 15.7% female and 52.8% ICM). fQRS was present in 46.7% of
      patients, predominantly inferior (30.7%) followed by anterior (21.4%) and lateral
      (11.1%) coronary artery territories. fQRS was significantly more prevalent in ICM
      (p=0.004). Inferior fQRS was an independent predictor of a first AS within 1y (HR
      2.55, 95%CI 1.28-5.07) and 3y (HR 1.90, 95%CI 1.14-3.18) after implantation.
      Whereas, anterior fQRS was an independent predictor of all-cause mortality within
      1y (HR 4.58, 95%CI 1.29-16.19), 3y (HR 3.92, 95%CI 1.77-8.65) and the complete
      follow-up (HR 2.22, 95%CI 1.33-3.69). Lateral fQRS was only a predictor of late
      (>3y of follow-up) all-cause mortality (HR 2.04, 95%CI 1.09-3.81). CONCLUSIONS:
      fQRS in a specific coronary artery territory might be promising to discriminate
      arrhythmic from mortality risk. Inferior fQRS was a predictor of early
      arrhythmia, while anterior fQRS was related to mortality.

PMID- 28747027
TI  - Colchicine for prevention of post-cardiac procedure atrial fibrillation: Meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Development of atrial fibrillation after certain cardiac procedures
      is a common medical problem. The inflammatory process plays an important role in
      the pathogenesis of post-cardiac procedure atrial fibrillation (PCP-AF).
      Colchicine, a potent anti-inflammatory agent, has been used in several studies to
      reduce the risk of PCP-AF. This meta-analysis of randomized controlled trials
      (RCTs) was conducted to assess the efficacy of colchicine in prevention of PC
      PAF. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library
      database and Google Scholar for RCTs, using terms "Atrial fibrillation, atrial,
      or fibrillation and colchicine". The primary end-point was the occurrence of AF
      post cardiac procedure, which includes cardiac surgery or pulmonary vein
      isolation. The safety end point was the occurrence of any side effects. Estimated
      odds ratios (OR) and 95% confidence intervals (CI) were evaluated. RESULTS: A
      total of six RCTs were included in this meta-analysis, enrolling a total of 1257
      patients. Colchicine significantly reduced the odds of PCP-AF (OR 0.52; 95% CI,
      0.40-0.68, P<0.001, I2=0%). However, occurrence of side effects was significantly
      higher with colchicine when compared to placebo (OR 2.10; 95% CI, 1.34-3.30,
      P<0.001, I2=0%). The number needed to treat is 7 and the number needed to harm is
      11.2. The proportion of patients discontinuing treatment was 16%. CONCLUSION:
      This meta-analysis shows that colchicine is an effective drug for prevention of
      PCP-AF. Colchicine could be considered as a prophylaxis to reduce PCP-AF, with
      some risk of treatment discontinuation due to the poor gastrointestinal tolerance
      (diarrhea).

PMID- 28747028
TI  - Atrial fibrillation: Applying evidence out of the box.

PMID- 28747029
TI  - Dynamic balance of platelet reactivity in atrial fibrillation PARtially
      unravelled.

PMID- 28747030
TI  - Prediction of benefits from prophylactic implantable cardioverter-defibrillator
      therapy.

PMID- 28747031
TI  - Role of triggers and substrate in heart failure based atrial fibrillation: Is
      pulmonary vein isolation still the cornerstone of atrial fibrillation therapy?

PMID- 28747032
TI  - A potential and lionhearted soldier for atrial fibrillation accompanied with
      heart failure: Renal denervation.

PMID- 28747033
TI  - Reply to letter to the editor: "A potential and lionhearted soldier for atrial
      fibrillation accompanied with heart failure: Renal denervation".

PMID- 28747034
TI  - Impact of peak provoked left ventricular outflow tract gradients on clinical
      outcomes in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is traditionally classified based
      on a left ventricular outflow tract (LVOT) pressure gradient of 30mmHg at rest or
      with provocation. There are no data on whether 30mmHg is the most informative cut
      off value and whether provoked gradients offer any information regarding
      outcomes. METHODS: Resting and provoked peak LVOT pressure gradients were
      measured by Doppler echocardiography in patients fulfilling guidelines criteria
      for HCM. A composite clinical outcome including new onset atrial fibrillation,
      ventricular tachycardia/fibrillation, heart failure, transplantation, and death
      was examined over a median follow-up period of 2.1years. RESULTS: Among 536
      patients, 131 patients had resting LVOT gradients greater than 30mmHg. Subjects
      with higher resting gradients were older with more cardiovascular events. For
      provoked gradients, a bi-modal risk distribution was found. Patients with
      provoked gradients >90mmHg (HR 3.92, 95% CI 1.97-7.79) or <30mmHg (HR 2.15, 95%
      CI 1.08-4.29) have more events compared to those with gradients between 30 and
      89mmHg in multivariable analysis. The introduction of two cut-off points for
      provoked gradients allowed HCM to be reclassified into four groups: patients with
      "benign" latent HCM (provoked gradient 30-89mmHg) had the best prognosis, whereas
      those with persistent obstructive HCM had the worst outcome. CONCLUSIONS:
      Provoked LVOT pressure gradients offer additional information regarding clinical
      outcomes in HCM. Applying cut-off points at 30 and 90mmHg to provoked LVOT
      pressure gradients further classifies HCM patients into low-, intermediate- and
      high-risk groups.

PMID- 28747035
TI  - Elevated circulating IL-32 presents a poor prognostic outcome in patients with
      heart failure after myocardial infarction.
AB  - BACKGROUND: Interleukin-32 (IL-32) is a newly discovered proinflammatory
      cytokine. However, there are limited data regarding IL-32 as a biomarker for
      heart failure (HF). In this study, we assessed the prognostic value of IL-32 in
      patients with chronic HF after myocardial infarction (MI). METHODS AND RESULTS:
      Over a period of 1.8years, we prospectively enrolled 100 patients with chronic HF
      after MI. IL-32, NT-proBNP, Matrix metallopeptidase 9 (MMP-9), procollagen type I
      (PI) and type III (PIII) were measured at baseline. Study endpoint was adverse
      cardiac events. High IL-32 levels were associated with numerous factors that are
      related to deteriorate cardiac function and cardiac fibrosis. Strong expression
      of IL-32 was detected in human cardiomyocytes from HF tissue. ROC curve revealed
      the area under the curve of IL-32 for predicting negative outcome of HF was 0.72
      (95% CI: 0.60-0.83, P<0.01). Kaplan-Meier statistics showed that the risk of
      adverse cardiac event was 5.75 fold (hazard ratio 5.75, 95% CI 1.53-21.58,
      P=0.009), which increased in the highest quartile (>296pg/mL). Cox regression
      analysis revealed IL-32 was an independent predictor for cardiac events (hazard
      ratio 2.78, 95% CI 1.02-7.57, P=0.046). Recombinant IL-32 significantly
      exacerbated infarct size in a mouse model of MI. IL-32 upregulated expression of
      MMP-9, PIII and transforming growth factor beta in rat fibroblasts. CONCLUSION:
      IL-32 might be a novel predictor of adverse cardiac event in patients with HF
      after MI. The pro-fibrotic effect of IL-32 may contribute to adverse cardiac
      remodeling and progression to HF.

PMID- 28747036
TI  - Long-term outcome of nonobstructive versus obstructive hypertrophic
      cardiomyopathy: A systematic review and meta-analysis.
AB  - BACKGROUND: Prognosis of hypertrophic cardiomyopathy (HCM) is particularly
      heterogeneous. Patients with nonobstructive HCM (NOCM) are thought to be at
      relatively low-risk as compared with obstructive HCM (HOCM) with no need of major
      treatment options. However, available evidence of NOCM comes mainly from tertiary
      centers where a referral bias is likely to occur. Aim of this study was to
      perform a systematic review and meta-analysis of the published literature on
      hypertrophic cardiomyopathy (HCM) in order to outline differences in presenting
      features and long-term outcome between NOCM and HOCM. METHODS: MEDLINE/Pubmed,
      EMBASE and Cochrane databases up to December 31, 2016, and reviewed cited
      references to identify relevant studies were used. The primary endpoints were HCM
      related overall mortality rate and yearly rate of cardiac death. Other endpoints
      were incidences of sudden and congestive heart failure deaths. RESULTS: A total
      of 20 studies entered the meta-analysis on the long-term outcome of NOCM vs HOCM.
      They included a total of 7731 patients, 5058 patients with NOCM (65%) and 2673
      patients with HOCM (35%). During the follow-up, annual mortality related to HCM
      averaged 1.55% in NOCM and 1.77% in HOCM (Relative Risk: 0.89, 95% confidence
      intervals: 0.68 to 1.17, p=0.40). Overall, 5 studies reported significantly
      higher mortality for HOCM, 3 higher mortality for NOCM, and 12 no significant
      differences. CONCLUSION: This large study-level meta-analysis shows that long
      term mortality of patients with NOCM is not negligible and not significantly
      different from HOCM.

PMID- 28747037
TI  - Increased arterial stiffness is an independent risk factor for hemorrhagic
      transformation in ischemic stroke undergoing thrombolysis.
AB  - BACKGROUND: Hemorrhagic transformation (HT) is a multifactorial phenomenon and
      represents a possible complication of ischemic stroke, especially after
      thrombolytic treatment. Increased arterial stiffness has been associated with
      intracranial hemorrhage, but there is no evidence of association with HT after
      thrombolytic therapy. The aim of our study is to investigate a possible link
      between arterial stiffness and HT occurrence after thrombolytic therapy in
      patients with ischemic stroke. METHODS: We enrolled 258 patients (135 males, 123
      females; mean age: 73+/-12years) with acute ischemic stroke undergoing
      intravenous thrombolysis or/and mechanical thrombectomy. All stroke patients
      underwent neuroimaging examination, 24-h heart rate and blood pressure monitoring
      and brain CT-scan after 24-72h to evaluate HT occurrence. The linear regression
      slope of diastolic on systolic blood pressure was obtained and assumed as a
      global measure of arterial compliance, and its complement (1 minus the slope),
      named arterial stiffness index (ASI), has been taken as a measure of arterial
      stiffness. RESULTS: Out of 258, HT occurred in 55 patients. ASI was significantly
      higher in patients with HT than in patients without HT (0.70+/-0.12 vs 0.62+/
      0.14, p<0.001). Logistic regression model showed ASI as independent predictors of
      HT (OR: 1.9, 95% CI: 1.09-3.02, for every 0.2 increase of ASI): in particular, OR
      was 5.2 (CI: 2.22-12.24) when ASI was >0.71, in comparison with ASI lower than
      0.57. CONCLUSIONS: Our results point to arterial stiffness as a novel independent
      risk factor for HT after ischemic stroke treated with thrombolysis, suggesting a
      particularly high bleeding risk when ASI is >0.71.

PMID- 28747038
TI  - Increased arterial stiffness and haemorrhagic transformation in ischaemic stroke
      after thrombolysis: A new marker of risk for cerebrovascular events and
      complications.

PMID- 28747039
TI  - Prior beta blockers use is independently associated with increased inpatient
      mortality in patients presenting with acute myocardial infarction.
AB  - BACKGROUND: Beta blockers (BBs) are recommended for patients presenting with
      acute myocardial infarction. However, the effects of prior BBs use on inpatient
      mortality in patients presenting with acute myocardial infarction (AMI) are
      unknown. METHODS: This was a retrospective cohort study of patients presenting
      with AMI in Florida Hospital Orlando from January 1, 2013 to December 31, 2014.
      Data were collected prospectively, as part of the Acute Coronary Treatment and
      Intervention Outcomes Network (ACTION) Registry. RESULTS: 1128 patients were
      included in the analysis, with 354 (31.4%) patients on home BBs and 774 (68.6%)
      not on home BBs on presentation. Patients in prior BBs group were older, had
      higher incidence of multiple comorbidities, and were more likely to take
      cardiovascular medications. During hospitalization, Patients in prior BBs group
      were more likely to develop decompensated heart failure (9.9% vs. 3.6%, P<0.001),
      less likely to have STEMI (33.9% vs. 54.4%, P<0.001), and subsequently less PCI
      (73.2% vs. 81.3%, P=0.002), but higher inpatient mortality (8.8% vs. 4.8%,
      P=0.009). In multivariable logistic regression analysis, prior BBs use was
      independently associated with increased inpatient mortality (adjusted OR 3.15,
      95% CI 1.44-6.87, P=0.004), as well as in GRACE model (adjusted ratio=1.83, 95%
      CI 1.01-3.34, P<0.047). However, prior BBs use did not contribute significantly
      to predict inpatient mortality on the basis of GRACE model in terms of
      discrimination and calibration. CONCLUSIONS: Prior BBs use was independently
      associated with increased inpatient mortality, and should be considered a high
      risk marker for patients presenting with acute myocardial infarction.

PMID- 28747040
TI  - Glycative and oxidative stress are associated with altered thrombus composition
      in diabetic patients with ST-elevation myocardial infarction.
AB  - BACKGROUND: The role of type 2 diabetes (T2DM) on composition of thrombus has not
      been fully characterized in patients with ST-elevation myocardial infarction
      (STEMI). AIMS: To elucidate the differences between diabetic and non-diabetic
      patients with STEMI in relation to the composition of coronary thrombus, and the
      potential association of these differences with glycated haemoglobin levels and
      markers of oxidative stress. METHODS: Intracoronary thrombi from consecutive
      thrombus aspiration procedures in STEMI patients, 25 diabetic and 28 non
      diabetic, were analyzed by immunofluorescence with confocal microscopy. Plasma
      biomarkers (P-selectin, vWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin
      and CD34+) were measured in peripheral blood, and the oxidative capacity of
      plasma as indirect measure of oxidative stress was measured in parallel. RESULTS:
      Patients with T2DM had higher levels of fibrin (P=0.03), P-selectin (P=0.0001),
      PAI-1 (P=0.03) and vWF (P=0.006) in the thrombus and higher plasma TF activity
      (P=0.01) compared to non-diabetics. TF activity and plasmin correlated with HbA1C
      levels (R2=0.71, P=0.0001; R2=0.46, P=0.04, respectively) and TF was inversely
      correlated with TFPI (R2=-0.44, P=0.008) and tPA (R2=-0.48, P=0.003). Diabetic
      patients showed a higher oxidative response of plasma (26.47+/-6.88% vs 22.06+/
      6.96% of oxidized lipids, P=0.04) (measured by H-NMR spectroscopy) that was
      associated to increased fibrin content into thrombus (R2=0.76, P=0.01).
      CONCLUSION: Diabetic patients with STEMI display an increased thrombogenicity
      that results in a different thrombus composition respect to non-diabetic patients
      with STEMI. The increased thrombogenicity present in T2DM is related to higher
      glycoxidative stress, as quantified by HbA1C levels and oxidative response in
      plasma.

PMID- 28747041
TI  - Influence of commercial inactivated yeast derivatives on the survival of
      probiotic bacterium Lactobacillus rhamnosus HN001 in an acidic environment.
AB  - This study evaluated the influence of three inactivated yeast derivatives (IYDs)
      used in wine production, namely OptiRed(r), OptiWhite(r) and Noblesse(r), on the
      viability of the probiotic strain Lactobacillus rhamnosus HN001 in an acidic
      environment. Addition of the IYDs at 3 g/L significantly enhanced the survival of
      the probiotic bacteria by 2.75-4.05 log cycles after 10-h exposure in a pH 3.0
      buffer. Acid stress assay with IYD components obtained after centrifugation and
      filtration revealed that water-soluble compounds were responsible for improving
      the acid tolerance of L. rhamnosus HN001 for all three preparations. Differences
      in protective effect amongst the IYDs on L. rhamnosus HN001 were observed when
      permeates and retentates of the water-soluble extracts, obtained through
      ultrafiltration with a 2 kDa membrane, were assayed against the lactic acid
      bacterium. Chemical analysis of the water-soluble components suggests that low
      molecular weight polysaccharides, specific free amino acids and/or antioxidants
      in the 2 kDa permeates could have contributed to the enhanced survival of L.
      rhamnosus HN001 during acid stress. The contrast amongst the 2 kDa retentates'
      viability enhancing property may have been attributed to the differences in size
      and structure of the higher molecular weight carbohydrates and proteins, as the
      survival of the probiotic did not relate to the concentration of these compounds.
      These results suggests that oenological IYDs could potentially be applied to
      probiotic foods for enhancing the acid tolerance of the beneficial
      microorganisms, and consequently prolonging the shelf life of these products.

PMID- 28747042
TI  - Broadband Perfect Absorber with Monolayer MoS2 and Hexagonal Titanium Nitride
      Nano-disk Array.
AB  - A broadband metamaterial absorber (MA) composed of hexagonal-arranged single
      sized titanium nitride (TiN) nano-disk array and monolayer molybdenum disulfide
      (MoS2) is studied using finite-difference time-domain (FDTD) simulations. The
      structure of TiN nano-disk array/dielectric silica (SiO2)/aluminum (Al) is
      adopted in our design. By optimizing the dimension parameters of the structure,
      an average absorption of 96.1% is achieved from 400 to 850 nm. In addition, by
      inserting a monolayer MoS2 which has high absorption at the short wavelength side
      underneath the TiN nano-disk array, an average absorption of 98.1% over the
      entire visible regime from 400 to 850 nm was achieved, with a peak absorption
      near 100% and absorption over 99% from 475 to 772 nm. Moreover, the absorber
      presented in this paper is polarization insensitive. This compact and unique
      design with TiN nano-disk/monolayer MoS2/ SiO2/Al structure may have great
      potential for applications in photovoltaics and light trapping.

PMID- 28747043
TI  - Hydrothermal synthesis of In2O3 nanoparticles hybrid twins hexagonal disk ZnO
      heterostructures for enhanced photocatalytic activities and stability.
AB  - In2O3 nanoparticles hybrid twins hexagonal disk (THD) ZnO with different ratios
      were fabricated by a hydrothermal method. The as-obtained ZnO/In2O3 composites
      are constituted by hexagonal disks ZnO with diameters of about 1 MUm and In2O3
      nanoparticles with sizes of about 20-50 nm. With the increase of In2O3 content in
      ZnO/In2O3 composites, the absorption band edges of samples shifted from UV to
      visible light region. Compared with pure ZnO, the ZnO/In2O3 composites show
      enhanced photocatalytic activities for degradation of methyl orange (MO) and 4
      nitrophenol (4-NP) under solar light irradiation. Due to suitable alignment of
      their energy band-gap structure of the In2O3 and ZnO, the formation of type p
      heterostructure can enhance efficient separation of photo-generate electro-hole
      pairs and provides convenient carrier transfer paths.

PMID- 28747044
TI  - Hydrothermal-Assisted Sintering Strategy Towards Porous- and Hollow-Structured
      LiNb3O8 Anode Material.
AB  - Porous- and hollow-structured LiNb3O8 anode material was prepared by a
      hydrothermal-assisted sintering strategy for the first time. The phase evolution
      was studied, and the formation mechanism of the porous and hollow structure was
      proposed. The formation of the unique structure can be attributed to the local
      existence of liquid phase because of the volatilization of Li element. As the
      anode material, the initial discharge capacity is 285.1 mAhg-1 at 0.1 C, the
      largest discharge capacity reported so far for LiNb3O8. Even after 50 cycles, the
      reversible capacity can still maintain 77.6 mAhg-1 at 0.1 C, about 2.5 times of
      that of LiNb3O8 samples prepared by traditional solid-state methods. The
      significant improvement of Li storage capacity can be attributed to the special
      porous and hollow structure, which provides a high density of active sites and
      short parallel channels for fast intercalation of Li+ ions through the surface.

PMID- 28747045
TI  - Molecular Dynamics Modeling and Simulation of Diamond Cutting of Cerium.
AB  - The coupling between structural phase transformations and dislocations induces
      challenges in understanding the deformation behavior of metallic cerium at the
      nanoscale. In the present work, we elucidate the underlying mechanism of cerium
      under ultra-precision diamond cutting by means of molecular dynamics modeling and
      simulations. The molecular dynamics model of diamond cutting of cerium is
      established by assigning empirical potentials to describe atomic interactions and
      evaluating properties of two face-centered cubic cerium phases. Subsequent
      molecular dynamics simulations reveal that dislocation slip dominates the plastic
      deformation of cerium under the cutting process. In addition, the analysis based
      on atomic radial distribution functions demonstrates that there are trivial phase
      transformations from the gamma-Ce to the delta-Ce occurred in both machined
      surface and formed chip. Following investigations on machining parameter
      dependence reveal the optimal machining conditions for achieving high quality of
      machined surface of cerium.

PMID- 28747046
TI  - Great Thermal Conductivity Enhancement of Silicone Composite with Ultra-Long
      Copper Nanowires.
AB  - In this paper, ultra-long copper nanowires (CuNWs) were successfully synthesized
      at a large scale by hydrothermal reduction of divalent copper ion using
      oleylamine and oleic acid as dual ligands. The characteristic of CuNWs is hard
      and linear, which is clearly different from graphene nanoplatelets (GNPs) and
      multi-wall carbon nanotubes (MWCNTs). The thermal properties and models of
      silicone composites with three nanomaterials have been mainly researched. The
      maximum of thermal conductivity enhancement is up to 215% with only 1.0 vol.%
      CuNW loading, which is much higher than GNPs and MWCNTs. It is due to the ultra
      long CuNWs with a length of more than 100 MUm, which facilitates the formation of
      effective thermal-conductive networks, resulting in great enhancement of thermal
      conductivity.

PMID- 28747047
TI  - Novel approach in using ultrasound in treating acute limb ischemia.
AB  - BACKGROUND: It is imperative to gain safe access into the occluded targeted
      vessel and begin treating acute extremity limb ischemia. Often the origin of the
      targeted native artery or bypass graft will have a flush occlusion making it
      difficult to cannulate. This paper looks at the novel use of portable ultrasound
      to evaluate the origin of the artery or bypass graft to help facilitate the start
      of thrombolysis. METHODS: We reviewed our last 2 years of acute limb ischemia in
      our patients with high risk factors and comorbidities. We reviewed the use of
      ultrasound in these cases from the initial use of gaining femoral access to real
      time ultrasound and fluoroscopic guidance into the targeted native artery or
      bypass graft to begin needed thrombolysis. RESULTS: We had 26 acute limb ischemia
      in 10 patients with native arterial circulation and in 16 patients with either
      saphenous or prosthetic bypass grafts. Ultrasound was used in gaining safe access
      with no complications in 22 contralateral and 2 antegrade femoral and 4 direct
      graft accesses. Ultrasound was used in 6 of these cases to help gain access in
      the occluded graft (4 cases) and saphenous veins (2 cases). It was successful in
      all cases but one case which had bleeding. CONCLUSIONS: Ultrasound is increasing
      in its application including acute limb ischemia with flush occlusions of native
      arteries and bypass grafts.

PMID- 28747049
TI  - Hospital mortality and its predictors in patients with infective endocarditis.

PMID- 28747048
TI  - Open-heart surgery in neonates: current practice.

PMID- 28747050
TI  - Density Gradation of Open Metal Sites in the Mesospace of Porous Coordination
      Polymers.
AB  - The prevalence of the condensed phase, interpenetration, and fragility of
      mesoporous coordination polymers (meso-PCPs) featuring dense open metal sites
      (OMSs) place strict limitations on their preparation, as revealed by experimental
      and theoretical reticular chemistry investigations. Herein, we propose a rational
      design of stabilized high-porosity meso-PCPs, employing a low-symmetry ligand in
      combination with the shortest linker, formic acid. The resulting dimeric clusters
      (PCP-31 and PCP-32) exhibit high surface areas, ultrahigh porosities, and high
      OMS densities (3.76 and 3.29 mmol g-1, respectively), enabling highly selective
      and effective separation of C2H2 from C2H2/CO2 mixtures at 298 K, as verified by
      binding energy (BE) and electrostatic potentials (ESP) calculations.

PMID- 28747051
TI  - Oxazine Ring-Related Vibrational Modes of Benzoxazine Monomers Using Fully
      Aromatically Substituted, Deuterated, 15N Isotope Exchanged, and Oxazine-Ring
      Substituted Compounds and Theoretical Calculations.
AB  - Polymerization of benzoxazine resins is indicated by the disappearance of a 960
      900 cm-1 band in infrared spectroscopy (IR). Historically, this band was assigned
      to the C-H out-of-plane bending of the benzene to which the oxazine ring is
      attached. This study shows that this band is a mixture of the O-C2 stretching of
      the oxazine ring and the phenolic ring vibrational modes. Vibrational frequencies
      of 3-phenyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (PH-a) and 3-(tert-butyl)-3,4
      dihydro-2H-benzo[e][1,3]oxazine (PH-t) are compared with isotope-exchanged and
      all-substituted compounds. Deuterated benzoxazine monomers, 15N-isotope exchanged
      benzoxazine monomers, and all-substituted benzoxazine monomers without aromatic C
      H groups are synthesized and studied meticulously. The various isotopic-exchanges
      involved deuteration around the benzene ring of phenol, selective deuteration of
      each CH2 in the O-CH2-N (2) and N-CH2-Ar (4) positions on the oxazine ring, or
      simultaneous deuteration of both positions. The chemical structures were
      confirmed by 1H nuclear magnetic resonance spectroscopy (1H NMR). The IR and
      Raman spectra of each compound are compared. Further analysis of 15N isotope
      exchanged PH-a indicates the influence of the nitrogen isotope on the band
      position, both experimentally and theoretically. This finding is important for
      polymerization studies of benzoxazines that utilize vibrational spectroscopy.

PMID- 28747052
TI  - Diagnostic and therapeutic features of small bowel involvement in portal
      hypertension.
AB  - Enteropathy is a lesser known complication of portal hypertension and consists of
      different changes in the mucosal layer of the small bowel which lead to the
      appearance of vascular and inflammatory lesions. It can be an important co-factor
      in the development of anemia in the cirrhotic population, and nowadays an easy
      and non-invasive diagnosis can be made thanks to capsule endoscopy. However, it
      is rarely considered in the management of patients with portal hypertension. Some
      aspects such as pathogenesis or incidence remain unclear and no specific
      recommendations are included in the guidelines regarding diagnosis or treatment.
      A review of the available literature was performed with regards to the most
      relevant aspects of this entity.

PMID- 28747053
TI  - Eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome.
      The SEPD perspective.
AB  - Functional gut disorders, including diarrhea-predominant irritable bowel
      syndrome, are highly prevalent conditions worldwide that significantly impact
      health economy and patient quality of life, yet lacking fully satisfactory
      therapeutic options. These circumstances fostered research on various molecules
      with more specific therapeutic targets, including opioid receptors. Eluxadoline
      (Allergan's Vibercy(r) in the USA, Truberzi(r) in Europe) is a locally-acting
      mixed mu- and kappa-opioid receptor agonist, and delta-opioid receptor
      antagonist, that was licensed in 2015 by the Food and Drug Administration (FDA)
      and in 2016 by the European Medicines Agency (EMA) for use in diarrhea
      predominant irritable bowel syndrome. Eluxadoline provides, with advantage over
      the current standard of care, control of both stool consistency and abdominal
      pain, good tolerability in most cases, and improved quality of life, hence it
      deserves consideration when approaching a patient with this disorder. As with any
      recently approved therapy, adequate pharmacovigilance is to be expected, as well
      as studies to inform on different scenarios such as on-demand therapy, loss of
      response assessment, use as rescue therapy for other molecules, and cost
      effectiveness, to further characterize and more accurately position eluxadoline
      within the therapeutic spectrum.

PMID- 28747054
TI  - Towards the centralization of digestive oncologic surgery: changes in activity,
      techniques and outcome.
AB  - AIM: The objective of the present study was to examine changes in the activity,
      surgical techniques and results from the process of centralization of complex
      digestive oncologic surgery in 2005-2012 as compared to 1996-2000. MATERIAL AND
      METHODS: A retrospective cohort study employing the minimum basic data set of
      hospital discharge (MBDSHD 1996-2012) from public centers in Catalonia (Spain)
      was performed. The population consisted of individuals aged > 18 who underwent
      digestive oncologic surgery (esophagus, pancreas, liver, stomach or rectum).
      Medical centers were divided into low, medium, and high-volume centers (<= 5, 6
      10, and > 10 interventions/year, respectively). The tendency Chi-squared test was
      used to assess the centralization of patients in high-volume centers and hospital
      mortality evolution during the study period. Logistic regression was performed to
      assess the relationship between volume and outcome. RESULTS: A centralization of
      complex oncologic digestive surgery between 10% (liver) and 46% (esophagus) was
      obtained by means of a reduction in the number of hospitals that perform these
      interventions and a significant rise in the number of patients operated in high
      volume centers (all types p <= 0.0001, except for esophagus). A significant
      decrease in mortality was observed, especially in esophagus (from 15% in
      1996/2000 to 7% in 2009/12, p = 0.003) and pancreas (from 12% in 1996/2000 to 6%
      in 2009/12, p trend < 0.0001). CONCLUSIONS: A centralization of oncologic
      digestive surgery in high-volume centers and a reduction of hospital mortality in
      Catalonia were reported among esophageal and pancreatic cancers. However, no
      significant changes were found for others cancer types.

PMID- 28747055
TI  - Cytomegalovirus: associated ischemic colitis in an immunocompetent patient.
AB  - Cytomegalovirus (CMV) colitis is a common entity in immunocompromised patients,
      being rare among immunocompetent individuals. In addition, its association with
      ischemic colitis is unusual in both groups of population. Rectal bleeding might
      occur in both entities and, occasionally, urgent surgical treatment may be
      required, associating high morbility rates. We report one case of cytomegalovirus
      colitis associated with severe ischemic colitis in a non- immunocompromised
      patient with favourable response to conservative management with antiviral
      therapy.

PMID- 28747056
TI  - Fecal transplantation as a treatment for Clostridium difficile infection in
      patients with ulcerative colitis.
AB  - Clostridium difficile (CD) infection is currently the most frequent etiology of
      nosocomial diarrhea. Besides, its incidence is progressively increasing in
      ambulatory patients. Inflammatory bowel disease (IBD) is a risk factor of CD
      infection itself, but also due to the regular immunosuppressive treatment used in
      these patients. At the present time, fecal transplantation (FT) is a safe and
      cost-effective alternative if the previous antibiotic treatments have failed.
      Similar outcomes between patients with IBD and general population have been
      reported. We present a case of a patient with ulcerative colitis and recurrent CD
      infection successfully treated with FT.

PMID- 28747057
TI  - Prevalence, risk factors and response to treatment of extra-intestinal
      manifestations in patients with inflammatory bowel disease.
AB  - INTRODUCTION: Patients with inflammatory bowel disease can experience extra
      intestinal manifestations that may cause significant morbidity. AIMS: To describe
      the prevalence, characteristics, treatment and evolution of extra-intestinal
      manifestations in inflammatory bowel disease patients treated in our hospital and
      to identify associated risk factors. METHODS: This was a retrospective,
      observational, case-control study. All inflammatory bowel disease patients with
      extra-intestinal manifestations were considered as cases and inflammatory bowel
      disease patients without extra-intestinal manifestations were considered as
      controls. RESULTS: Six hundred and nineteen patients with inflammatory bowel
      disease (327 Crohn's disease, 265 ulcerative colitis, 27 indeterminate colitis)
      were included in the study; 16.5% experienced at least one extra-intestinal
      manifestation (CI 95% 13.5-19.5; n = 102). The most frequent extra-intestinal
      manifestations observed were musculoskeletal (n = 50; 40%) and cutaneous
      manifestations (n = 50; 40%). With regard to treatment, arthropathies were
      treated with non-steroidal anti-inflammatory drugs (31%) and corticosteroids
      (19%, oral or intra-articular), and the majority of the cutaneous manifestations
      were managed with corticosteroids. Overall, the efficacy of extra-intestinal
      manifestation treatment was 90% and only 13% of patients had a recurrence of
      extra-intestinal manifestations. The multivariate analysis showed that female
      gender (p = 0.012; OR = 1.61; 95% CI 1.11-2.34) and the severity of inflammatory
      bowel disease (p = 0.009; OR = 1.65; 95% CI 1.13-2.4 if immunosuppressant therapy
      alone, or p = 0.029; OR = 2.28; 95% CI 1.09-4.78 if in combination with
      adalimumab) were associated with an increased risk of developing extra-intestinal
      manifestations. CONCLUSIONS: The most frequent extra-intestinal manifestations in
      our environment were musculoskeletal and cutaneous manifestations. Female gender
      and a more severe disease were associated with a higher risk of developing extra
      intestinal manifestations. Individualized treatment of extra-intestinal
      manifestations is effective and the risk is low in our series.

PMID- 28747058
TI  - Pancreatic enzyme replacement therapy in cystic fibrosis: dose, variability and
      coefficient of fat absorption.
AB  - OBJECTIVES: Pancreatic enzyme replacement therapy (PERT) remains a backbone in
      the nutritional treatment of cystic fibrosis. Currently, there is a lack of an
      evidence-based tool that allows dose adjustment. To date, no studies have found
      an association between PERT dose and fat absorption. Therefore, the aim of the
      study was to assess the influence of both the PERT dose and the variability in
      this dose on the coefficient of fat absorption (CFA). METHODS: This is a
      retrospective longitudinal study of 16 pediatric patients (192 food records) with
      three consecutive visits to the hospital over a twelve-month period. Dietary fat
      intake and PERT were assessed via a four-day food record and fat content in
      stools was determined by means of a three-day stool sample collection. A beta
      regression model was built to explain the association between the CFA and the
      interaction between the PERT dose (lipase units [LU]/g dietary fat) and the
      variability in the PERT dose (standard deviation [SD]). RESULTS: The coefficient
      of fat absorption increased with the PERT dose when the variability in the dose
      was low. In contrast, even at the highest PERT dose values, the CFA decreased
      when the variability was high. The confidence interval suggested an association,
      although the analysis was not statistically significant. CONCLUSION: The
      variability in the PERT dose adjustment should be taken into consideration when
      performing studies on PERT efficiency. A clinical goal should be the maintenance
      of a constant PERT dose rather than trying to obtain an optimal value.

PMID- 28747059
TI  - Rectal inflammatory stenosis secondary to Chlamydia trachomatis: a case report.
AB  - The rectal inflammatory originated strictures constitute a rare cause of
      intestinal obstruction. We present a 30-year-old male patient with a history of
      HIV and protctitis caused by Chalmydia trachomatis and HSV-2, in which develops a
      low intestinal obstruction refractory to medical treatment. Surgery was performed
      with good clinical evolution. The medical treatment constitutes the fundamental
      basis of the therapy in these patients. Despite that, when fibrotic stenoses are
      not treatable medical or endoscopically, they often require surgical treatment.
      We must pay attention to the proctitis infectious diseases as a cause of rectal
      stenosis, especially by Chlamydia trachomatis, and assess surgical option in
      refractory cases.

PMID- 28747060
TI  - Treatment persistence during therapeutic sequences with adalimumab and infliximab
      in the treatment of Crohn's disease.
AB  - BACKGROUND AND AIM: Tumor necrosis factor (TNF) inhibitors have demonstrated
      efficacy and safety in the treatment Crohn's disease (CD). However, the loss of
      response over time means that they are usually used sequentially. The aim of this
      study was to compare treatment persistence with different sequences of TNF
      inhibitors in patients with active luminal CD. METHODS: A Markov model (3-month
      cycles) was developed to simulate the therapeutic sequences of beginning
      biological treatment with infliximab or adalimumab, with a time horizon of three
      years. Each state of the model represented treatment (induction, standard dose or
      escalated dose) with each TNF inhibitor or the state without biological
      treatment. The transition probabilities between states were determined by the
      clinical response to TNF inhibitors obtained from the literature. The likelihood
      of discontinuation due to adverse effects was also considered. RESULTS: After
      three years, the percentage of CD patients receiving infliximab and adalimumab as
      a first TNF inhibitor that remained in treatment was 52.8% and 59.3% (p = 0.1)
      respectively. Median time to discontinuation of the standard dose was 26.26
      months in patients who started with adalimumab and 24.39 months in patients who
      started with infliximab. CONCLUSION: In the model, there were no significant
      differences in persistence after three years with the initial drug among patients
      with active luminal CD starting treatment with infliximab or adalimumab.

PMID- 28747061
TI  - Endovascular Treatment for Steno-Occlusive Iliac Artery Disease: Safety and Long
      Term Outcome.
AB  - We evaluated safety and long-term outcome of endovascular therapy for steno
      occlusive iliac artery disease. All endovascular procedures of iliac artery
      lesions performed at our institution between 2001 and 2014 (n = 676) were
      retrospectively analyzed. The overall technical success rate was 99% and yielded
      100% for stenoses (n = 596) and 95% for chronic total occlusions (n = 80). Lesion
      complexity defined by the Trans-Atlantic Inter-Society Consensus (TASC) II
      classification had no impact on success rates (TASC A + B vs C + D; 99.5% vs
      98.6%, P = .359). During a median follow-up of 11 months, the overall rate of
      restenosis was 9.4%. After 1 and 3 years, the primary patency rates were 94% and
      86% and the secondary patency rate was 100%, respectively. The TASC II
      classification had no impact on long-term patency rates (TASC A + B vs C + D; 86%
      vs 81%). In a multivariable analysis, stent diameter remained the only
      significant predictor for restenosis (hazard ratio: 0.58; 95% confidence
      interval: 0.41%-0.81%; P = .002). In this single-center retrospective study,
      endovascular therapy for steno-occlusive iliac artery disease was associated with
      high technical and clinical success rates as well as an excellent long-term
      patency rate irrespective of lesion complexity.

PMID- 28747062
TI  - Re: Placebo responses in device studies.

PMID- 28747063
TI  - DPP4 Inhibitors Can Be a Drug of Choice for Type 3 Diabetes: A Mini Review.
AB  - As well known to the scientific community, Alzheimer's disease (AD) is an
      irreversible neurodegenerative disease that ends up with impairment of memory and
      cognition due to neuronal and synapse loss. Patient's quality of life can be
      enhanced by targeting neurogenesis as a therapeutic paradigm. Moreover, several
      research evidences support the concept that AD is a type of metabolic disorder
      mediated by impairment in brain insulin responsiveness and energy metabolism.
      Growing evidence suggests that endogenous peptides such as glucagon-like peptide
      1 (GLP-1) and stromal-derived factor-1alpha (SDF-1alpha) provide neuroprotection
      across a range of experimental models of AD. So, preserving functional activity
      of SDF-1alpha and GLP-1 by dipeptidyl peptidase-4 inhibition will enhance the
      homing/recruitment of brain resident and nonresident circulating stem
      cells/progenitor cells, a noninvasive approach for promoting neurogenesis. So,
      herewith we provide this in support of dipeptidyl peptidase-4 inhibitors as a new
      target of attention for treating AD.

PMID- 28747064
TI  - Graph Lasso-Based Test for Evaluating Functional Brain Connectivity in Sickle
      Cell Disease.
AB  - Sickle cell disease (SCD) is a vascular disorder that is often associated with
      recurrent ischemia-reperfusion injury, anemia, vasculopathy, and strokes. These
      cerebral injuries are associated with neurological dysfunction, limiting the full
      developing potential of the patient. However, recent large studies of SCD have
      demonstrated that cognitive impairment occurs even in the absence of brain
      abnormalities on conventional magnetic resonance imaging (MRI). These
      observations support an emerging consensus that brain injury in SCD is diffuse
      and that conventional neuroimaging often underestimates the extent of injury. In
      this article, we postulated that alterations in the cerebral connectivity may
      constitute a sensitive biomarker of SCD severity. Using functional MRI, a
      connectivity study analyzing the SCD patients individually was performed. First,
      a robust learning scheme based on graphical lasso model and Frechet mean was used
      for estimating a consistent descriptor of healthy brain connectivity. Then, we
      tested a statistical method that provides an individual index of similarity
      between this healthy connectivity model and each SCD patient's connectivity
      matrix. Our results demonstrated that the reference connectivity model was not
      appropriate to model connectivity for only 4 out of 27 patients. After
      controlling for the gender, two separate predictors of this individual similarity
      index were the anemia (p = 0.02) and white matter hyperintensities (WMH) (silent
      stroke) (p = 0.03), so that patients with low hemoglobin level or with WMH have
      the least similarity to the reference connectivity model. Further studies are
      required to determine whether the resting-state connectivity changes reflect
      pathological changes or compensatory responses to chronic anemia.

PMID- 28747065
TI  - Use of granulocyte-colony stimulating factor to prevent recurrent clozapine
      induced neutropenia on drug rechallenge: A systematic review of the literature
      and clinical recommendations.
AB  - BACKGROUND: Clozapine is the most effective medication for treatment-refractory
      schizophrenia; however, its use is contraindicated in people who have had
      previous clozapine-induced neutropenia. Co-prescription of granulocyte-colony
      stimulating factor may prevent recurrent neutropenia and allow continuation or
      rechallenge of clozapine. OBJECTIVE AND METHODS: Systematic review of literature
      reporting the use of granulocyte-colony stimulating factor to allow rechallenge
      or continuation of clozapine in people with previous episodes of clozapine
      induced neutropenia. The efficacy of granulocyte-colony stimulating factor and
      predictors of successful rechallenge will be determined to elucidate whether
      evidence-based recommendations can be made regarding the use of granulocyte
      colony stimulating factor in this context. RESULTS: A total of 17 articles were
      identified that reported on clozapine rechallenge with granulocyte-colony
      stimulating factor support. In all, 76% of cases were able to continue clozapine
      at median follow-up of 12 months. There were no clear clinical or laboratory
      predictors of successful rechallenge; however, initial neutropenia was more
      severe in successful cases compared to unsuccessful cases. Cases co-prescribed
      lithium had lower success rates of rechallenge (60%) compared to those who were
      not prescribed lithium (81%). The most commonly reported rechallenge strategy was
      use of filgrastim 150-480 ug between daily to three times a week. There were no
      medication-specific side effects of granulocyte-colony stimulating factor
      reported apart from euphoria in one case. Three cases who failed granulocyte
      colony stimulating factor had bacterial infection at time of recurrent
      neutropenia. No deaths were reported. CONCLUSION: Preliminary data suggest
      granulocyte-colony stimulating factor is safe and effective in facilitating
      rechallenge with clozapine. Clinical recommendations for use are discussed.

PMID- 28747066
TI  - Mental wellbeing in people with dementia following Cognitive Stimulation Therapy:
      Innovative practice.
AB  - The benefits of Cognitive Stimulation Therapy in supporting cognitive functioning
      for people with dementia are well recognised. It has been proposed that Cognitive
      Stimulation Therapy may offer additional benefits in terms of a person's sense of
      general wellbeing. A service evaluation of 60 participants attending Cognitive
      Stimulation Therapy groups was conducted using the Short Warwick-Edinburgh Mental
      Well-Being Scale. Although this evaluation did not demonstrate a significant
      difference between pre- and post-treatment scores (t = -1.75, df = -59, p = 
      0.085), there was a trend in participants' reported optimism about the future and
      confidence. Recommendations about future research in relation to mental wellbeing
      in dementia care are discussed.

PMID- 28747067
TI  - RAS mutation prevalence among patients with metastatic colorectal cancer: a meta
      analysis of real-world data.
AB  - AIM: A confirmed wild-type RAS tumor status is commonly required for prescribing
      anti-EGFR treatment for metastatic colorectal cancer. This noninterventional,
      observational research project estimated RAS mutation prevalence from real-world
      sources. MATERIALS & METHODS: Aggregate RAS mutation data were collected from 12
      sources in three regions. Each source was analyzed separately; pooled prevalence
      estimates were then derived from meta-analyses. RESULTS: The pooled RAS mutation
      prevalence from 4431 tumor samples tested for RAS mutation status was estimated
      to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to
      54.1% (95% CI: 51.7-56.5%) between sources. CONCLUSION: The RAS mutation
      prevalence estimates varied among sources. The reasons for this are not clear and
      highlight the need for further research.

PMID- 28747068
TI  - A Dual AMPK/Nrf2 Activator Reduces Brain Inflammation After Stroke by Enhancing
      Microglia M2 Polarization.
AB  - AIMS: Microglia-mediated neuroinflammation plays an important role in focal
      ischemic stroke, a disorder with no effective therapeutic agents. Since
      microglial polarization to the M2 phenotype and reduction of oxidative stress are
      mediated through AMP-activated protein kinase (AMPK) and nuclear factor erythroid
      2-related factor 2 (Nrf2) activation, we assessed the dual therapeutic effect of
      AMPK and Nrf2 activation by a novel neuroprotectant HP-1c in the treatment of
      ischemic stroke. RESULTS: We developed a novel class of hybrids (HP-1a-HP-1f) of
      telmisartan and 2-(1-hydroxypentyl)-benzoate (HPBA) as a ring-opening derivative
      of NBP. The most promising hybrid, HP-1c, exhibited more potent anti-inflammatory
      and neuroprotective effects in vitro and reduced brain infarct volume and
      improved neurological deficits in a rat model of transient focal cerebral
      ischemia when compared with telmisartan alone, NBP alone, or a combination of
      telmisartan and NBP. HP-1c had a therapeutic window of up to 24 h, ameliorated
      ischemic cerebral injury in permanent focal cerebral ischemia, and improved motor
      function. The beneficial effects of HP-1c in ischemic stroke were associated with
      microglial polarization to the M2 phenotype and reduced oxidative stress. HP-1c
      also shifted the M1/M2 polarization in a mouse neuroinflammatory model. The anti
      inflammatory and anti-oxidative effects of HP-1c were associated with AMPK-Nrf2
      pathway activation for neuroprotection. We showed that HP-1c penetrates the
      brain, has a plasma half-life of around 3.93 h, and has no toxicity in mice.
      Innovation and Conclusion: Our study results suggest that HP-1c, with dual AMPK-
      and Nrf2-activating properties, may have potential in further studies as a novel
      therapy for ischemic stroke. Antioxid. Redox Signal. 28, 141-163.

PMID- 28747070
TI  - Hooked on a feeling: Repetitive cognition and internalizing symptomatology in
      relation to autism spectrum symptomatology.
AB  - Repetitive cognition, including rumination such as that seen in depression, has
      been shown to correlate with depression symptoms in both typically developing
      individuals and individuals with autism spectrum disorder. Repetitive cognition
      is more common in autism spectrum disorder than in typically developing peers, as
      is depression; thus, this study evaluated the role of repetitive cognition in
      relation between autism spectrum symptomatology and depressive symptomatology. In
      all, 200 typically developing adults completed self-report questionnaires
      measuring autism spectrum symptomatology, different forms of repetitive cognition
      (general perseveration and depressive rumination), depression, and rejection
      sensitivity. Perseveration was found to mediate the relation between autism
      spectrum symptoms and depression, and to partially mediate the relation between
      autism spectrum symptoms and rejection sensitivity. We conclude that it is of
      vital importance to consider cognition when considering depression in autism
      spectrum disorder.

PMID- 28747069
TI  - A Proposal of the Modification of Japanese Society on Thrombosis and Hemostasis
      (JSTH) Disseminated Intravascular Coagulation (DIC) Diagnostic Criteria for
      Sepsis-Associated DIC.
AB  - Sepsis-associated disseminated intravascular coagulation (DIC) carries a high
      risk of death. Thus, a simple tool to quickly establish DIC diagnosis is
      required. The purpose of this study was to introduce the simple and reliable tool
      for the prediction of outcome in patients with sepsis complicated by
      coagulopathy. We investigated the performance of simplified Japanese Society on
      Thrombosis and Hemostasis (JSTH) DIC diagnostic criteria. In this study, we
      conducted a retrospective, multicenter survey in 107 general emergency and
      critical care centers in secondary and tertiary care hospitals. A total of 918
      patients with sepsis-associated coagulopathy who underwent antithrombin
      supplementation were examined. The relationships between patient mortality and
      each of the baseline (ie, before treatment) JSTH-DIC diagnostic criteria were
      examined. A reduced platelet count, increased prothrombin time (PT) ratio, and
      lower antithrombin activity were correlated with 28-day mortality, while
      fibrinogen and fibrin degradation product (FDP) level were not. Thus, the number
      of points assigned to FDP levels was reduced from 3 to 1 (above 20 MUg/mL). The
      simplified JSTH diagnostic criteria combining platelet count, PT ratio,
      antithrombin activity, and FDP level (reduction in the maximum score) strongly
      predicted 28-day mortality and allowed us to diagnose a larger/similar number of
      patients with DIC as compared to the original JSTH-DIC. The simplified JSTH-DIC
      diagnostic criteria show a similar performance to JSTH-DIC criteria in patients
      with septic coagulopathy. The lower number of laboratory markers used in the
      simplified JSTH-DIC score may increase its applicability and routine use in
      emergency and critical care setting.

PMID- 28747071
TI  - A Hibernation-Like State for Transplantable Organs: Is Hydrogen Sulfide Therapy
      the Future of Organ Preservation?
AB  - SIGNIFICANCE: Renal transplantation is the treatment of choice for end-stage
      renal disease, during which renal grafts from deceased donors are routinely cold
      stored to suppress metabolic demand and thereby limit ischemic injury. However,
      prolonged cold storage, followed by reperfusion, induces extensive tissue damage
      termed cold ischemia/reperfusion injury (IRI) and puts the graft at risk of both
      early and late rejection. Recent Advances: Deep hibernators constitute a natural
      model of coping with cold IRI as they regularly alternate between 4 degrees C and
      37 degrees C. Recently, endogenous hydrogen sulfide (H2S), a gas with a
      characteristic rotten egg smell, has been implicated in organ protection in
      hibernation. CRITICAL ISSUES: In renal transplantation, H2S also seems to confer
      cytoprotection by lowering metabolism, thereby creating a hibernation-like
      environment, and increasing preservation time while allowing cellular processes
      of preservation of homeostasis and tissue remodeling to take place, thus
      increasing renal graft survival. FUTURE DIRECTIONS: Although the underlying
      cellular and molecular mechanisms of organ protection during hibernation have not
      been fully explored, mammalian hibernation may offer a great clinical promise to
      safely cold store and reperfuse donor organs. In this review, we first discuss
      mammalian hibernation as a natural model of cold organ preservation with
      reference to the kidney and highlight the involvement of H2S during hibernation.
      Next, we present recent developments on the protective effects and mechanisms of
      exogenous and endogenous H2S in preclinical models of transplant IRI and evaluate
      the potential of H2S therapy in organ preservation as great promise for renal
      transplant recipients in the future. Antioxid. Redox Signal. 28, 1503-1515.

PMID- 28747072
TI  - Regulation of Staphylococcus aureus Infection of Macrophages by CD44, Reactive
      Oxygen Species, and Acid Sphingomyelinase.
AB  - AIMS: Staphylococcus aureus plays an important role in sepsis, pneumonia, and
      wound infections. Acid sphingomyelinase (Asm)-deficient mice are highly
      susceptible to pulmonary S. aureus infections. Here, we investigated the role of
      CD44 as a molecule that mediates important aspects of the infection of
      macrophages with S. aureus. RESULTS: We showed that CD44 activation by S. aureus
      stimulated Asm via the formation of reactive oxygen species, resulting in
      ceramide release, clustering of CD44 in ceramide-enriched membrane platforms,
      CD44/Asm-dependent activation of Rho family GTPases, translocation of phospho
      ezrin/radixin/moesin to the plasma-membrane, and a rapid rearrangement of the
      actin cytoskeleton with cortical actin polymerization. Genetic deficiency of CD44
      or Asm abrogated these signaling events and thereby reduced internalization of S.
      aureus into macrophages by 60-80%. Asm-deficient macrophages also exhibited
      reduced fusion of phagosomes with lysosomes, which prevented intracellular
      killing of S. aureus in macrophages and thereby allowed internalized S. aureus to
      replicate and cause severe pneumonia. Innovation and Conclusion: The CD44-Asm
      ceramide system plays an important role in the infection of macrophages with S.
      aureus. Antioxid. Redox Signal. 00, 000-000.

PMID- 28747073
TI  - The Osler's view: Treating comorbid bipolar disorder and obsessive-compulsive
      disorder.

PMID- 28747074
TI  - Commentary on Grady et al.: Using poor, uninsured minorities to test the safety
      of experimental drugs.

PMID- 28747075
TI  - Current management of spontaneous coronary artery dissection.
AB  - INTRODUCTION: Spontaneous coronary artery dissection (SCAD) remains an infrequent
      and elusive clinical entity of unknown etiology. However, our knowledge of SCAD
      has been significantly enriched in recent years. Large and prospective
      contemporary series have increased the interest in this disease with fewer
      patients misdiagnosed and a growing number of cases recognized in daily clinical
      practice. Classically, SCAD was thought to present mainly in young women without
      traditional atherosclerotic risk factors but, actually, most patients are middle
      aged and are not free from coronary risk factors. A high number of associated
      conditions have been reported. Of these, fibromuscular dysplasia emerges as a
      major association with intriguing pathophysiological implications. Areas covered:
      This review aims to present a contemporary update on SCAD. We concentrate on the
      clinical scenario, related conditions, practical management and treatment
      strategies. Expert commentary: Recognition of SCAD is currently much more
      frequent and accurate as a result of increased clinical awareness and the
      widespread use of intravascular imaging techniques. Hopefully, in the near future
      an improvement in the management of SCAD patients will come not only from
      empirical evidence but also from dedicated clinical trials.

PMID- 28747076
TI  - A global, incremental development method for a web-based prostate cancer
      treatment decision aid and usability testing in a Dutch clinical setting.
AB  - Many new decision aids are developed while aspects of existing decision aids
      could also be useful, leading to a sub-optimal use of resources. To support
      treatment decision-making in prostate cancer patients, a pre-existing evidence
      based Canadian decision aid was adjusted to Dutch clinical setting. After
      analyses of the original decision aid and routines in Dutch prostate cancer care,
      adjustments to the decision aid structure and content were made. Subsequent
      usability testing (N = 11) resulted in 212 comments. Care providers mainly
      provided feedback on medical content, and patients commented most on usability
      and summary layout. All participants reported that the decision aid was
      comprehensible and well-structured and would recommend decision aid use. After
      usability testing, final adjustments to the decision aid were made. The presented
      methods could be useful for cultural adaptation of pre-existing tools into other
      languages and settings, ensuring optimal usage of previous scientific and
      practical efforts and allowing for a global, incremental decision aid development
      process.

PMID- 28747077
TI  - Sandwich Technique for Endovascular Repair of Acute Type A Aortic Dissection.
AB  - OVERVIEW: To describe a new endovascular procedure for acute type A aortic
      dissection (TAAD) repair. METHODS: Between 2013 and 2016, 12 patients (average
      age 54+/-9.6 years; 10 men) with acute TAAD (mean EURO score 11.4%+/-3.2%, range
      5-17) and unfit for surgery underwent thoracic endovascular aortic repair (TEVAR)
      with 2 periscope grafts to preserve blood supply to supra-aortic branches plus
      bypass grafting as needed. If the ascending aorta was dilated to >40 mm,
      sternotomy was performed to wrap the ascending aorta and reduce its diameter to
      accommodate the aortic stent-grafts. RESULTS: All patients were successfully
      treated. Seven patients required bypass grafting, and most of the patients had
      periscope grafts to the innominate/right common carotid artery and left common
      carotid artery; only 3 patients had the left subclavian artery preserved. All
      patients exhibited good hemodynamics and normal pressures after the procedure.
      The mean procedure time and blood loss were 4.5+/-1.0 hours and 217+/-111.5 mL,
      respectively. Two patients treated emergently died shortly after surgery from
      multiorgan failure. The average follow-up duration was 17+/-14.5 months (range 2
      42) in the 10 survivors. The remaining patients recovered and none experienced
      stent-graft thrombosis, stroke, or peripheral artery embolism during follow-up.
      CONCLUSION: A procedure that combines sandwich/periscope grafting with TEVAR,
      wrapping of the aorta, and supra-arch bypass grafting can be used to treat
      patients with acute TAAD.

PMID- 28747078
TI  - Users' perceptions on digital visualization of neuropathic cancer-related pain.
AB  - Quality pain management implies a thorough pain assessment with structured
      communication between patients and healthcare providers. Pain distribution is an
      important dimension of cancer pain. Assessment of pain distribution is commonly
      performed on a pain body map. This study explores how a computerized pain body
      map may function as a communication tool and visualize pain in patients with
      advanced cancer. In previous studies, we have developed a tablet-based
      computerized pain body map for use in cancer patients. The aim of this study was
      to adapt the computerized pain body map program to patients with neuropathic
      cancer-related pain, and to develop a separate interface for healthcare
      providers. We also wanted to investigate the perceived usefulness of this system
      among patients and healthcare providers. Both patients and healthcare providers
      perceived that the visualization of pain in the computerized pain body map system
      had potential to be a positive contribution to clinical pain management, and to
      improve collaboration between healthcare providers.

PMID- 28747079
TI  - Endovascular Repair of a Thoracoabdominal Aortic Aneurysm With a Patient-Specific
      Fenestrated-Branched Stent-Graft.
AB  - PURPOSE: To describe the technical aspects of a thoracoabdominal aortic aneurysm
      (TAAA) repair using a patient-specific fenestrated-branched stent-graft.
      TECHNIQUE: The technique is demonstrated in a 69-year-old man with a 6.2-cm
      asymptomatic type III TAAA. A patient-specific fenestrated-branched stent-graft
      was designed with 2 down-going directional branches for the celiac and superior
      mesenteric arteries and 2 reinforced fenestrations for the renal arteries. The
      procedure was performed under general anesthesia and included sequential stenting
      of the celiac, superior mesenteric, and bilateral renal arteries. The patient was
      discharged from the hospital on postoperative day 5 with no complications. Follow
      up computed tomography angiography demonstrated exclusion of the aneurysm and
      patent target vessels at 12-month follow-up. CONCLUSION: This article and
      illustrated video highlight the steps for procedure planning and implantation of
      fenestrated and branched endografts. As these techniques continue to evolve,
      outcomes are expected to be equivalent or improved as compared to those of long
      established open repair.

PMID- 28747080
TI  - External validation of a rectal cancer outcome prediction model with a cohort of
      patients treated with preoperative radiochemotherapy and deep regional
      hyperthermia.
AB  - PURPOSE: To validate a nomogram for the prediction of treatment outcomes after
      preoperative radiochemotherapy and surgery for locally advanced rectal cancer
      with a cohort of patients treated with additional deep regional hyperthermia.
      PATIENTS AND METHODS: A total of 86 patients were treated with preoperative
      radiochemotherapy and deep regional hyperthermia at our institution. For every
      patient, the 5-year probability for death, distant metastases and local failure
      based on a previously published nomogram were calculated and patients were
      divided into three risk groups. RESULTS: Low-lying and clinically lymph node
      positive tumours were more frequent in the validation cohort. Five-year Kaplan
      Meier estimates for overall survival (OS), distant metastases-free survival
      (DMFS) and local control (LC) were 87.3%, 79.9%, 95.8% (observed) and 75.5%, 71%,
      90% (predicted), respectively. Discrimination between low- and high-risk groups
      was at a significant level for all endpoints. The c-index was 0.81 (OS), 0.67
      (DMFS) and 0.92 (LC), respectively. CONCLUSIONS: The nomogram showed reasonable
      performance when deep regional hyperthermia is incorporated into preoperative
      therapy. The higher than predicted rates seen for OS and DMFS in particular in
      the high-risk groups warrant further prospective validation and subsequent
      investigation of the underlying mechanisms.

PMID- 28747081
TI  - Fabrication, characterization, and in vitro study of zinc substituted
      hydroxyapatite/silk fibroin composite coatings on titanium for biomedical
      applications.
AB  - Zinc substituted hydroxyapatite/silk fibroin composite coatings were deposited on
      titanium substrates at room temperature by electrophoretic deposition.
      Microscopic characterization of the synthesized composite nanoparticles revealed
      that the particle size ranged 50-200 nm, which increased a little after zinc
      substitution. The obtained coatings maintained the phase of hydroxyapatite and
      they could induce fast apatite formation in simulated body fluid, indicating high
      bone activity. The cell culturing results showed that the biomimetic
      hydroxyapatite coatings could regulate adhesion, spreading, and proliferation of
      osteoblastic cells. Furthermore, the biological behavior of the zinc substituted
      hydroxyapatite coatings was found to be better than the bare titanium without
      coatings and hydroxyapatite coatings without zinc, increasing MC3T1-E1 cell
      differentiation in alkaline phosphatase expression.

PMID- 28747082
TI  - Construction of functional pancreatic artificial islet tissue composed of
      fibroblast-modified polylactic- co-glycolic acid membrane and pancreatic stem
      cells.
AB  - Objective To improve the biocompatibility between polylactic- co-glycolic acid
      membrane and pancreatic stem cells, rat fibroblasts were used to modify the
      polylactic- co-glycolic acid membrane. Meanwhile, we constructed artificial islet
      tissue by compound culturing the pancreatic stem cells and the fibroblast
      modified polylactic- co-glycolic acid membrane and explored the function of
      artificial islets in diabetic nude mice. Methods Pancreatic stem cells were
      cultured on the fibroblast-modified polylactic- co-glycolic acid membrane in
      dulbecco's modified eagle medium containing activin-A, beta-catenin, and exendin
      4. The differentiated pancreatic stem cells combined with modified polylactic- co
      glycolic acid membrane were implanted subcutaneously in diabetic nude mice. The
      function of artificial islet tissue was explored by detecting blood levels of
      glucose and insulin in diabetic nude mice. Moreover, the proliferation and
      differentiation of pancreatic stem cells on modified polylactic- co-glycolic acid
      membrane as well as the changes on the tissue structure of artificial islets were
      investigated by immunofluorescence and haematoxylin and eosin staining. Results
      The pancreatic stem cells differentiated into islet-like cells and secreted
      insulin when cultured on fibroblast-modified polylactic- co-glycolic acid
      membrane. Furthermore, when the artificial islet tissues were implanted into
      diabetic nude mice, the pancreatic stem cells combined with polylactic- co
      glycolic acid membrane modified by fibroblasts proliferated, differentiated, and
      secreted insulin to reduce blood glucose levels in diabetic nude mice. Conclusion
      Pancreatic stem cells can be induced to differentiate into islet-like cells in
      vitro. In vivo, the artificial islet tissue can effectively regulate the blood
      glucose level in nude mice within a short period. However, as time increased, the
      structure of the artificial islets was destroyed due to the erosion of blood
      cells that resulted in the gradual loss of artificial islet function.

PMID- 28747083
TI  - A Novel Variant with Positive Natural Selection Influenced Hb A2 Levels in
      Chinese Individuals with beta-Thalassemia.
AB  - beta-Thalassemia (beta-thal) is the most common inherited hemolytic anemia
      worldwide. Elevated Hb A2 is a mark of beta-thal carriers. The aim of this study
      was to identify the pathogenic variants associated with the Hb A2 levels. One
      thousand and thirty beta-thal carriers were recruited for this study. Using
      positive natural expression quantitative trait loci (eQTL) analysis, a
      significant variant was selected. Genotyping for the rs231841 polymorphism was
      performed by the Sequenom MassARRAY IPLEX platform. All genetic association
      analyses were performed with the PLINK program. The linear regression analysis
      showed that rs231841 in the intron region of the potassium voltage-gated channel
      subfamily Q member 1 (KCNQ1) gene on chromosome 11p15 was significantly
      associated with Hb A2 levels. The presence of the C allele was associated with
      elevated Hb A2 levels. Our results suggest that rs231841 on the KCNQ1 gene with
      positive natural selection is related to Hb A2 levels in Chinese beta-thal
      carriers, and KCNQ1 is probably associated with the expression of the beta-like
      globin gene cluster.

PMID- 28747085
TI  - Predictors in starting and stopping Internet use between 2002 and 2012 by Dutch
      adults 65 years and older.
AB  - Research has indicated the need to consider the ageing process with technology
      adoption by older adults. This study examined psychological, health, social and
      demographic predictors with starting and stopping Internet use by older adults
      (2002-2012). Data were used from the Longitudinal Aging Study Amsterdam, and Cox
      regression analyses were done to test predictors over time with starting or
      stopping Internet use. The results indicated that older adults starting to use
      the Internet (11.6%) outnumbered those who stopped (3.1%). Psychological, health,
      social and demographic predictors separately predicted starting and stopping
      Internet use. Starting use was predicted by lower age, higher education, normal
      cognition and living alone. The predictors in stopping use were being younger,
      having a high sense of mastery and being higher educated. The results need to be
      interpreted as indicative due to the small number of stoppers. Suggestions are
      made on how to improve usability.

PMID- 28747084
TI  - MiR-615-5p depresses natural killer cells cytotoxicity through repressing IGF-1R
      in hepatocellular carcinoma patients.
AB  - miR-615-5p was characterized by our group as a tumour suppressor. IGF-1 R
      activates a downstream signalling pathway, well characterized in liver cells,
      however, its role in immunity especially Natural Killer cells (NKs) remains
      vague. This study aimed at investigating the regulatory role of miR-615-5p on IGF
      signalling and its impact on NKs cytotoxicity in HCC. Our results showed an
      upregulation in miR-615-5p and IGF-1 R in NKs of 130 HCC patients compared to 35
      controls. Forcing the expression of miR-615-5p, repressed IGF-IR, attenuated NKs
      cytotoxicity, decreased CD56dim, increased CD56bright NK subsets and reduced the
      cytotoxic markers NKG2D, TNF-alpha and perforins. It repressed NKG2D ligand
      (ULBP2) in Huh-7 cells. In conclusion, miR-615-5p represses IGF-1 R in NKs and
      their target hepatocytes; however, it has a contradicting impact on HCC
      progression on both cell types. These findings might pave the way for better
      understanding the role of microRNAs in NKs function and HCC immune-pathogenesis.

PMID- 28747086
TI  - Menthol enhances nicotine-induced locomotor sensitization and in vivo functional
      connectivity in adolescence.
AB  - Mentholated cigarettes capture a quarter of the US market, and are
      disproportionately smoked by adolescents. Menthol allosterically modulates
      nicotinic acetylcholine receptor function, but its effects on the brain and
      nicotine addiction are unclear. To determine if menthol is psychoactive, we
      assessed locomotor sensitization and brain functional connectivity. Adolescent
      male Sprague Dawley rats were administered nicotine (0.4 mg/kg) daily with or
      without menthol (0.05 mg/kg or 5.38 mg/kg) for nine days. Following each
      injection, distance traveled in an open field was recorded. One day after the
      sensitization experiment, functional connectivity was assessed in awake animals
      before and after drug administration using magnetic resonance imaging. Menthol
      (5.38 mg/kg) augmented nicotine-induced locomotor sensitization. Functional
      connectivity was compared in animals that had received nicotine with or without
      the 5.38 mg/kg dosage of menthol. Twenty-four hours into withdrawal after the
      last drug administration, increased functional connectivity was observed for
      ventral tegmental area and retrosplenial cortex with nicotine+menthol compared to
      nicotine-only exposure. Upon drug re-administration, the nicotine-only, but not
      the menthol groups, exhibited altered functional connectivity of the dorsal
      striatum with the amygdala. Menthol, when administered with nicotine, showed
      evidence of psychoactive properties by affecting brain activity and behavior
      compared to nicotine administration alone.

PMID- 28747087
TI  - Safety and effectiveness of once-daily Hysingla extended-release tablets in
      patients with baseline depression or anxiety.
AB  - AIM: Long-term safety and effectiveness of a once-daily, single-entity, extended
      release formulation of hydrocodone bitartrate (HYD) for the treatment of moderate
      to severe noncancer and nonneuropathic pain among patients with and without
      concurrent depression/anxiety at baseline. MATERIALS & METHODS: Post hoc
      analysis. RESULTS: HYD demonstrated a safety profile consistent with MU-opioid
      agonists: Serious adverse events in 12% patients with depression/anxiety
      including four deaths; 6% without depression/anxiety including one death. All
      pain scores declined by >=2 points and mean daily HYD dose remained stable in
      both subgroups. CONCLUSION: More serious adverse events occurred among patients
      with comorbid depression/anxiety at baseline than among those without. HYD
      provided stable and effective analgesia for 52 weeks among chronic pain patients
      with and without comorbid depression/anxiety at baseline.

PMID- 28747088
TI  - Hierarchical Bayes approach for subgroup analysis.
AB  - In clinical data analysis, both treatment effect estimation and consistency
      assessment are important for a better understanding of the drug efficacy for the
      benefit of subjects in individual subgroups. The linear mixed-effects model has
      been used for subgroup analysis to describe treatment differences among subgroups
      with great flexibility. The hierarchical Bayes approach has been applied to
      linear mixed-effects model to derive the posterior distributions of overall and
      subgroup treatment effects. In this article, we discuss the prior selection for
      variance components in hierarchical Bayes, estimation and decision making of the
      overall treatment effect, as well as consistency assessment of the treatment
      effects across the subgroups based on the posterior predictive p-value. Decision
      procedures are suggested using either the posterior probability or the Bayes
      factor. These decision procedures and their properties are illustrated using a
      simulated example with normally distributed response and repeated measurements.

PMID- 28747089
TI  - Advances in nanopore sensing promises to transform healthcare.
AB  - International Conference on Nanopore Technology (Shenzhen), 30 March-1 April
      2017, Shenzhen, China The International Conference on Nanopore Technology
      (Shenzhen) was held from 30 March to 1 April 2017 in Shenzhen, China. The goal of
      the meeting was threefold: leverage the unique properties of nanopore technology
      to promote transformative advances in medicine, encourage cross-disciplinary
      collaborations in the research community within China and abroad; and discuss
      critical challenges that need to be addressed to rapidly advance the field. The
      meeting was chaired by Peixuan Guo, Endowed chair professor and Director of The
      Center for RNA Nanobiotechnology & Nanomedicine at The Ohio State University, USA
      and co-chaired by Xian-En Zhang, distinguished professor of the Institute of
      Biophysics, Chinese Academy of Sciences, China. The conference was attended by
      more than 300 academic researchers, hospital administrators, government leaders
      and scientists from many disciplines across the country from both academic
      institutions and industry.

PMID- 28747090
TI  - Retrospective evaluation of milk production and culling risk following either
      surgical, toggle-pin suture or conservative treatment of left displaced abomasum
      in Chilean dairy cows.
AB  - AIMS To describe milk yield and culling risk in cows diagnosed with left
      displacement of abomasum (LDA) treated either conservatively, by right flank
      pyloric omentopexy, or rolling and toggling, compared with normal herdmates from
      four Chilean dairy herds. METHODS Historical records were obtained from four
      commercial dairy farms located in Central Chile for cows with a history of LDA
      between 2010 and 2012, and healthy herdmates. Cows with LDA were categorised into
      three groups: cows treated with right omentopexy (ST, n=58), cows treated by
      toggle suturing (TT, n=15) and cows treated conservatively (CT, n=56). Control
      cows (n=129) were selected from unaffected cows, matched by days in milk (DIM),
      parity and herd with affected cows. Groups were compared for risk of culling up
      to 300 DIM and for milk production up to 5 months of lactation using survival and
      Cox proportional hazard models and mixed models for repeated measures,
      respectively. RESULTS Compared with cows in the Control group, the risk of being
      culled up to 300 DIM was 9.1 (SE 0.62) times greater in ST cows, 10.4 (SE 0.68)
      times greater in TT cows, and 37.3 (SE 0.61) times greater in CT cows (p<0.01).
      In the first 5 months of lactation, compared with cows in the Control group, mean
      daily milk production was 23.3 (SE 1.5) kg less in ST cows, 15.3 (SE 1.6) kg less
      in TT cows, and 30.1 (SE 1.3) kg less in CT cows (p<0.001). CONCLUSIONS AND
      CLINICAL RELEVANCE Cows in four dairy herds in central Chile diagnosed and
      treated for LDA produced significantly less milk and had a higher risk of culling
      than healthy herdmates. Although cows treated surgically or with toggle suture
      never recovered to the extent of healthy cows, they produced more milk than cows
      treated conservatively. However, the retrospective nature of the data, the
      inclusion of only four herds and the non-random allocation to treatments means
      that these conclusions cannot be extrapolated to the overall dairy cattle
      population in Chile.

PMID- 28747091
TI  - District nurses' experiences of caring for leg ulcers in accordance with clinical
      guidelines: a grounded theory study.
AB  - This qualitative study used the grounded theory method to investigate district
      nurses' experiences of caring for leg ulcers in accordance with clinical
      guidelines at seven primary health care centres in Stockholm, Sweden. Group
      interviews were conducted with 30 nurses. The results describe how district
      nurses strive to stay on track in order to follow clinical guidelines and remain
      motivated despite prolonged wound treatment and feelings of hopelessness. Three
      main obstacles to following the guidelines were found. District nurses used
      compensating strategies so the obstacles would not lead to negative consequences.
      If the compensating strategies were insufficient, perceived prolonged wound
      treatment and feelings of hopelessness could result. District nurses then used
      motivating strategies to overcome these feelings of hopelessness. Sometimes,
      despite the motivating strategies, treatment in accordance with guidelines could
      not be achieved. With some patients, district nurses had to compromise and follow
      the guidelines as far as possible.

PMID- 28747092
TI  - Clinical Features of a Family with Multiple Endocrine Neoplasia Type 2A Caused by
      the D631Y RET Mutation.
AB  - We describe a family with multiple endocrine neoplasia type 2A (MEN2A) caused by
      the D631Y RET mutation resulting in an atypical phenotype. The index case was a
      24-year-old man with history of recurrent anaplastic ependymoma incidentally
      found to have the D631Y RET mutation. At first assessment, four family members
      had evidence of large pheochromocytomas. One patient was found to have
      micromedullary thyroid cancer at 79 years of age. None of the patients had
      primary hyperparathyroidism. Patients with MEN2A caused by a D631Y RET mutation
      most commonly present with pheochromocytomas. Medullary thyroid cancer is a less
      common part of the syndrome when compared with other RET mutations.

PMID- 28747093
TI  - Prochlorperazine Increases KCC2 Function and Reduces Spasticity after Spinal Cord
      Injury.
AB  - In mature neurons, low intracellular chloride level required for inhibition is
      maintained by the potassium-chloride cotransporter, KCC2. Impairment of Cl-
      extrusion after KCC2 dysfunction has been involved in many central nervous system
      disorders, such as seizures, neuropathic pain, or spasticity, after a spinal cord
      injury (SCI). This makes KCC2 an appealing drug target for restoring Cl-
      homeostasis and inhibition in pathological conditions. In the present study, we
      screen the Prestwick Chemical Library(r) and identify conventional antipsychotics
      phenothiazine derivatives as enhancers of KCC2 activity. Among them,
      prochlorperazine hyperpolarizes the Cl- equilibrium potential in motoneurons of
      neonatal rats and restores the reciprocal inhibition post-SCI. The compound
      alleviates spasticity in chronic adult SCI rats with an efficacy equivalent to
      the antispastic agent, baclofen, and rescues the SCI-induced downregulation of
      KCC2 in motoneurons below the lesion. These pre-clinical data support
      prochlorperazine for a new therapeutic indication in the treatment of spasticity
      post-SCI and neurological disorders involving a KCC2 dysfunction.

PMID- 28747094
TI  - A comparison of socioeconomic status and mental health among inner-city
      Aboriginal and non-Aboriginal women.
AB  - Aboriginal women in urban areas have been reported to experience high rates of
      poverty, homelessness, interpersonal violence, and health problems. However,
      there are few prior ethnocultural comparisons of urban women from similar
      socioeconomic backgrounds. The current study explored the mental and physical
      health of Aboriginal and non-Aboriginal women accessing social services agencies
      and shelters. Half of the sample (n=172) was Aboriginal (48.3%). The lifetime
      rate of physical abuse was significantly higher in Aboriginal women, and they
      were more likely to have been victims of violence or crime in the past year
      (A=50.6%, NA=35.6%, p<0.05). Rates of teenage pregnancy (<18 years of age) were
      significantly higher among Aboriginals (A=51.3%, NA=30.6%, p<0.05) and they
      reported more parental drug/alcohol problems (A=79.2%, NA=56.5%, p<0.05).
      Aboriginal women were also more likely to have previously received treatment for
      a drug or alcohol problem. There were no differences in self-reported physical
      health, medication use, hospitalisations, and current substance misuse.
      Irrespective of ethnicity, lifetime rates of anxiety, depression and suicide
      attempts were extremely high. Future research should explore the effects of
      individual resources (e.g. social support, family relations) and cultural beliefs
      on women's ability to cope with the stress of living with adverse events,
      particularly among low SES women with children.

PMID- 28747095
TI  - Simulation-based sensitivity analysis for non-ignorably missing data.
AB  - Sensitivity analysis is popular in dealing with missing data problems
      particularly for non-ignorable missingness, where full-likelihood method cannot
      be adopted. It analyses how sensitively the conclusions (output) may depend on
      assumptions or parameters (input) about missing data, i.e. missing data
      mechanism. We call models with the problem of uncertainty sensitivity models. To
      make conventional sensitivity analysis more useful in practice we need to define
      some simple and interpretable statistical quantities to assess the sensitivity
      models and make evidence based analysis. We propose a novel approach in this
      paper on attempting to investigate the possibility of each missing data mechanism
      model assumption, by comparing the simulated datasets from various MNAR models
      with the observed data non-parametrically, using the K-nearest-neighbour
      distances. Some asymptotic theory has also been provided. A key step of this
      method is to plug in a plausibility evaluation system towards each sensitivity
      parameter, to select plausible values and reject unlikely values, instead of
      considering all proposed values of sensitivity parameters as in the conventional
      sensitivity analysis method. The method is generic and has been applied
      successfully to several specific models in this paper including meta-analysis
      model with publication bias, analysis of incomplete longitudinal data and mean
      estimation with non-ignorable missing data.

PMID- 28747096
TI  - Preliminary description of aging cats and dogs presented to a New Zealand first
      opinion veterinary clinic at end-of-life.
AB  - AIMS To conduct a preliminary investigation into the chronic disease conditions
      and clinical signs present in aging New Zealand companion animals at end-of-life
      and to describe the timing, circumstances, and manner of death. METHODS The
      medical records database of a first-opinion, companion animal, veterinary
      practice in Auckland, New Zealand was searched to identify all canine and feline
      patients >=7 years of age that were subjected to euthanasia or cremated in the
      period between July 2012-June 2014. The free-text medical notes were analysed for
      information on the circumstances surrounding the death, previous diagnoses of
      chronic disease conditions, and the presence of clinical signs associated with
      decreased quality-of-life at the time of euthanasia. RESULTS The median age at
      death was 15 (max 22) years for the 130 cats and 12 (max 17) years for the 68
      dogs in the study sample. Euthanasia at the clinic was carried out for 119/130
      (91%) cats and 62/68 (91%) dogs, with the remainder recorded as having an
      unassisted death. The frequency of deaths was highest during December for both
      cats and dogs. Cost was mentioned as an issue in the medical records for 39/181
      (21.6%) patients that were subjected to euthanasia. At the time of euthanasia,
      92/119 (77.3%) cats and 43/62 (69.4%) dogs were recorded as having >1 clinical
      sign associated with a decreased quality-of-life. Inappetence and non-specific
      decline were the two most commonly recorded clinical signs for both dogs and
      cats. Cardiovascular disease (44/130, 34%), renal failure (40/130, 31%), and
      malignant neoplasia (36/130, 28%) were the most common chronic disease conditions
      recorded for cats. Degenerative joint disease (22/68, 32%), malignant neoplasia
      (14/68, 21%), and cardiovascular disease (8/68, 12%) were the most common chronic
      disease conditions recorded for dogs. CONCLUSIONS AND CLINICAL RELEVANCE These
      preliminary findings highlight that aging companion animals in New Zealand
      frequently have chronic disease conditions and clinical signs that may
      potentially be associated with decreased quality-of-life at the time of death.
      Further in-depth studies are required to determine whether there is a greater
      role for veterinarians in counselling owners about end-of-life care and
      euthanasia decisions.

PMID- 28747097
TI  - * Tissue Engineering Strategies to Improve Osteogenesis in the Juvenile Swine
      Alveolar Cleft Model.
AB  - Alveolar (gumline) clefts are the most common congenital bone defect in humans,
      affecting 1 in 700 live births. Treatment to repair these bony defects relies on
      autologous, cancellous bone transfer from the iliac crest. This harvest requires
      a second surgical site with increased surgical time associated with potential
      complications, while providing only limited cancellous bone. Improvements in
      treatment protocols that avoid these limitations would be beneficial to patients
      with clefts and other craniofacial bone defects. There have been steady advances
      in tissue-engineered (TE) solutions for long-bone defects and adult patients, but
      advances for the pediatric craniofacial skeleton have been slower to emerge. This
      study utilizes a previously established juvenile swine model with a surgically
      created, critical size alveolar defect to test the efficacy of umbilical cord
      (UC) mesenchymal stem cells (MSCs) treatments on nano-microfiber scaffolds. At 1
      month after implanting our TE construct, mineralized tissue in the surgical gap
      was quantified through computed tomography (CT), and histology, and excised
      tissue was subjected to mechanical testing. Both undifferentiated and
      predifferentiated (toward an osteogenic lineage) UC MSCs generated bone within
      the cleft on a scale comparable to iliac crest cancellous bone, as evidenced by
      histology and CT scans. All of the pigs treated with scaffold/stem cell
      combinations had mineralized tissue within the defect, although without filling
      the entire defect. Several of the experimental animals exhibited poor and/or
      asymmetric maxillary growth 1 month after the initial surgery, especially if the
      surgical defect was located on the smaller side of an already asymmetric pig. Our
      results demonstrate that tissue engineering approaches using UC MSCs are a
      promising alternative for repair of the alveolar cleft. Data in the pig model
      demonstrate that implanted scaffolds are at least as good as the current gold
      standard treatment based on harvesting cancellous bone from the iliac crest,
      regardless of whether the cells seeded on the scaffold are precommitted to an
      osteogenic fate.

PMID- 28747098
TI  - Effect of Mesenchymal Stromal Cells on T Cells in a Septic Context:
      Immunosuppression or Immunostimulation?
AB  - Sepsis is a complex process, including a first wave of damage partially due to
      the body's response to pathogens, followed by a phase of immune cell dysfunction.
      The efficacy of a pharmacological approach facing a rapidly evolving system
      implies a perfect timing of administration-this difficulty could explain the
      recent failure of clinical trials. Mesenchymal stromal cells (MSCs) are usually
      defined as immunosuppressive and their beneficial effects in preclinical models
      of acute sepsis have been shown to rely partly on such ability. If nonregulated,
      this phenotype could be harmful in the immunosuppressed context arising hours
      after sepsis onset. However, MSCs being environment sensitive, we hypothesized
      that they could reverse their immunosuppressive properties when confronted with
      suffering immune cells. Our objective was to evaluate the effect of human MSCs on
      activated human lymphocytes in an in vitro endotoxemia model. Peripheral blood
      mononuclear cells (PBMCs) underwent a 24-h lipopolysaccharide (LPS) intoxication
      and were stimulated with phytohemagglutinin (PHA) in contact with MSCs. MSCs
      induced a differential effect on lymphocytes depending on PBMC intoxication with
      LPS. Unintoxicated lymphocytes were highly proliferative with PHA and were
      inhibited by MSCs, whereas LPS-intoxicated lymphocytes showed a low proliferation
      rate, but were supported by MSCs, even when monocytes were depleted. These data,
      highlighting MSC plasticity in their immunomodulatory activity, pave the way for
      further studies investigating the mechanisms of mutual interactions between MSCs
      and immune cells in sepsis. Thus, MSCs might be able to fight against both early
      sepsis-induced hyperinflammatory response and later time points of immune
      dysfunction.

PMID- 28747099
TI  - * In Vivo Models for the Evaluation of the Osteogenic Potency of Bone Substitutes
      Seeded with Mesenchymal Stem Cells of Human Origin: A Concise Review.
AB  - Research concerning bone substitutes is one of the most challenging fields in
      orthopedic research and has a high clinical relevance, especially since the
      currently available bone substitutes are limited in their osteostimulative
      capabilities. In vitro models for the evaluation of the properties of bone
      substitutes allow the use of human mesenchymal stem cells (hMSCs) seeded onto
      scaffolds, but suffer from the lack of a physiological environment for those
      cells. Most in vivo models include the use of non-hMSC and are therefore lacking
      in clinical relevance. To overcome these issues, in vivo models were created that
      allow the evaluation of hMSC-seeded bone substitutes, combining the advantages of
      the use of human cells with the physiological conditions of an organism in vivo.
      In brief, models usually aim for bone formation in immunocompromised rodents. The
      subcutaneous implantation of scaffolds is most widely performed, showing low
      complication rates along with good results, but suffering from inferior
      vascularization of the implants and the absence of the realistic structural and
      mechanical conditions of bone. Orthotopic implantation, for example in calvarian
      or long bone defects, provides the most appropriate surrounding for hMSC-seeded
      scaffolds. However, parallel host-induced bone formation is a major limitation.
      This review summarizes in vivo models for the evaluation of the osteogenic
      potency of bone substitutes seeded with mesenchymal stem cells of human origin.

PMID- 28747100
TI  - Loading and elution characteristics of quadrasphere microspheres loaded with
      bevacizumab.
AB  - AIM: Super absorbent polyvinyl alcohol-sodium acrylate copolymer microspheres,
      Quadrasphere microspheres (QSM), are commonly used for drug-eluting bead therapy,
      however, the literature only reports its use with small molecule
      chemotherapeutics. This study evaluates the loading and elution characteristics
      of bevacizumab-loaded QSM. METHODS & RESULTS: A single vial of QSM was
      reconstituted with 200 mg of bevacizumab. Drug concentration was determined by
      ELISA immunoassay. At approximately 90 min, there was maximal loading at 59% of
      the starting dose. In vitro elution demonstrated 52% of bound bevacizumab was
      released within the first hour and 68% by 16 h. CONCLUSION: Bevacizumab can load
      onto QSM and elute over time. This targeted delivery vehicle may potentially
      result in more effective treatment and fewer complications related to systemic
      toxicity.

PMID- 28747101
TI  - [5-year course of dyslexia - Persistence, sex effects, performance in reading and
      spelling, and school-related success].
AB  - Objective: The study examines the 5-year course of children with dyslexia with
      regard to their sex. Furthermore, the study investigates the impact of dyslexia
      on the performance in reading and spelling skills and school-related success.
      Method: A group of 995 6- to 16-year-olds were examined at the initial
      assessment. Part of the initial sample was then re-examined after 43 and 63
      months. The diagnosis of dyslexia was based on the double discrepancy criterion
      using a standard deviation of 1.5. Though they had no intellectual deficits, the
      children showed a considerable discrepancy between their reading or writing
      abilities and (1) their nonverbal intelligence and (2) the mean of their grade
      norm. Results: Nearly 70 % of those examined had a persisting diagnosis of
      dyslexia over a period of 63 months. The 5-year course was not influenced by sex.
      Despite average intelligence, the performance in writing and spelling of children
      suffering from dyslexia was one standard deviation below a control group without
      dyslexia with average intelligence and 0.5 standard deviations below a group of
      children suffering from intellectual deficits. Furthermore, the school-related
      success of the dyslexics was significantly lower than those of children with
      average intelligence. Dyslexics showed similar school-related success rates to
      children suffering from intellectual deficits. Conclusions: Dyslexia represents a
      considerable developmental risk. The adverse impact of dyslexia on school-related
      success supports the importance of early diagnostics and intervention. It also
      underlines the need for reliable and general accepted diagnostic criteria. It is
      important to define such criteria in light of the prevalence rates.

PMID- 28747103
TI  - A deliberative framework to identify the need for real-life evidence building of
      new cancer drugs after interim funding decision.
AB  - BACKGROUND: With the rising cost of new oncology treatments, it is no longer
      sustainable to base initial drug funding decisions primarily on prospective
      clinical trials as their performance in real-life populations are often difficult
      to determine. In British Columbia, an approach in evidence building is to
      retrospectively analyse patient outcomes using observational research on an ad
      hoc basis. METHODS: The deliberative framework was constructed in three stages:
      framework design, framework validation and treatment programme characterization,
      and key informant interview. Framework design was informed through a literature
      review and analyses of provincial and national decision-making processes.
      Treatment programmes funded between 2010 and 2013 were used for framework
      validation. A selection concordance rate of 80% amongst three reviewers was
      considered to be a validation of the framework. Key informant interviews were
      conducted to determine the utility of this deliberative framework. RESULTS: A
      multi-domain deliberative framework with 15 assessment parameters was developed.
      A selection concordance rate of 84.2% was achieved for content validation of the
      framework. Nine treatment programmes from five different tumour groups were
      selected for retrospective outcomes analysis. Five contributory factors to
      funding uncertainties were identified. Key informants agreed that the framework
      is a comprehensive tool that targets the key areas involved in the funding
      decision-making process. CONCLUSIONS: The oncology-based deliberative framework
      can be routinely used to assess treatment programmes from the major tumour sites
      for retrospective outcomes analysis. Key informants indicate this is a value
      added tool and will provide insight to the current prospective funding model.

PMID- 28747102
TI  - Irinotecan-induced muscle twitching from a possible drug interaction: A case
      report.
AB  - We report the case of a 50-year-old human immunodeficiency virus-positive patient
      with stage IV KRAS-mutated colorectal cancer who experienced visible muscle
      twitching in the right lateral triceps brachii from irinotecan administration for
      which typical supportive care measures were unsuccessful, including the
      administration of atropine and slowing down the infusion rate. The patient was
      able to tolerate this reaction and received 20 cycles of irinotecan-based
      chemotherapy despite experiencing the muscle twitching with every cycle at the
      same onset, duration, and severity. It is possible that competitive metabolism by
      concomitant medications metabolized by CYP3A4 or UGT1A1 was responsible for this
      event. Due to ethical concerns, we were unable to formally assess the drug
      interaction by discontinuing the suspected interacting medications and re
      initiating them to evaluate the effects. A formal pharmacokinetic study may be
      warranted to better elucidate these potential drug interactions.

PMID- 28747104
TI  - Indigenous Australian women's colonial sexual intimacies: positioning indigenous
      women's agency.
AB  - Colonialist views of Indigenous bodies and sexualities continue to affect
      Indigenous peoples worldwide. For Indigenous Australians, this burden has
      resulted in repression and oppression of power, sex and desire. Focusing on the
      sexual intimacies of Indigenous Australian women, this paper provides an account
      of the dominant Australian historical discourses, finding that Indigenous women
      were viewed as exotic, erotic, something to be desired, yet simultaneously
      something to be feared. Our sexualities were described as savage, promiscuous and
      primitive and we were often viewed as prostitutes with our voices and views
      constrained by patriarchal and imperial regimes of power. But within this
      context, Indigenous women fought back through both individual and collective acts
      of agency. This paper demonstrates how Indigenous Australian women's agency not
      as a new phenomenon but rather as a position that disrupts the popular discourses
      of exploitation and victimhood that have been persistently perpetrated against
      Indigenous women.

PMID- 28747106
TI  - Citation of prior research has increased in introduction and discussion sections
      with time: A survey of clinical trials in physiotherapy.
AB  - BACKGROUND/AIMS: Many clinical trials are reported without reference to the
      existing relevant high-quality research. This study aimed to investigate the
      extent to which authors of reports of clinical trials of physiotherapy
      interventions try to use high-quality clinical research to (1) help justify the
      need for the trial in the introduction and (2) help interpret the trial's results
      in the discussion. METHODS: Data were extracted from 221 clinical trials that
      were randomly selected from the Physiotherapy Evidence Database: 70 published in
      2001 (10% sample) and 151 published in 2015 (10% sample). The Physiotherapy
      Evidence Database score (which rates methodological quality and completeness of
      reporting) for each trial was also downloaded. RESULTS: Overall 41% of trial
      reports cited a systematic review or the results of a search for other evidence
      in the introduction section: 20% for 2001 and 50% for 2015 (relative risk = 2.3,
      95% confidence interval = 1.5-3.8). For the discussion section, only 1 of 221
      trials integrated the results of the trial into an existing meta-analysis, but
      citation of a relevant systematic review did increase from 17% in 2001 to 34% in
      2015. There was no relationship between citation of existing research and the
      total Physiotherapy Evidence Database score. CONCLUSION: Published reports of
      clinical trials of physiotherapy interventions increasingly cite a systematic
      review or the results of a search for other evidence in the introduction, but
      integration with existing research in the discussion section is very rare. To
      encourage the use of existing research, stronger recommendations to refer to
      existing systematic reviews (where available) could be incorporated into
      reporting checklists and journal editorial guidelines.

PMID- 28747107
TI  - Rejoinder.

PMID- 28747108
TI  - An alternative aide-memoire to assist in the clinical assessment of suicidal
      patients: comment on Alyami et al.

PMID- 28747109
TI  - The changing face of posttraumatic stress disorder in modern warfare.
AB  - OBJECTIVES: This study examined aspects of modern warfare and determined whether
      they have changed the clinical presentation of posttraumatic stress disorder
      (PTSD). CONCLUSIONS: The relationship between PTSD, mild traumatic brain injury,
      unmanned aerial vehicle operations and women in combat examined. It was concluded
      that there are significant changes in how contemporary combat veterans may
      present with PTSD.

PMID- 28747110
TI  - No role for benzodiazepines in posttraumatic stress disorder until supported by
      evidence.

PMID- 28747111
TI  - PTSD: the need to use emerging knowledge to improve systems of care and clinical
      practice in Australia.

PMID- 28747113
TI  - Developing a metformin prescribing tool for use in adults with mental illness to
      reduce medication-related weight gain and cardiovascular risk.
AB  - OBJECTIVES: There is considerable evidence that metformin reduces weight gain
      associated with antipsychotic medication. The aim of this study was to develop an
      easy-to-use metformin prescribing tool in order to enable clinicians to prescribe
      metformin safely and confidently. METHODS: The authors undertook a survey of
      clinicians and reviewed the published literature and existing guidelines
      concerning the use of metformin to reduce weight gain in adults with mental
      illness. RESULTS: A metformin prescribing tool was devised based on the
      literature, national cardiovascular and diabetes guidelines and Australian
      metformin prescribing recommendations. The metformin prescribing tool guides
      clinicians through the considerations required for appropriate selection of the
      target patient population and safe prescription of metformin. CONCLUSIONS: A
      novel, easy-to-use, one-page reference has been developed for busy clinicians
      that can be laminated and displayed in consulting rooms and psychiatric inpatient
      units to address weight gain and obesity associated with antipsychotic
      medications in people with mental illness.

PMID- 28747114
TI  - Prevalence, characteristics and management of headache experienced by people with
      schizophrenia and schizoaffective disorder: a cross sectional cohort study.
AB  - OBJECTIVES: Headache is the most common type of pain reported by people with
      schizophrenia. This study aimed to establish prevalence, characteristics and
      management of these headaches. METHODS: One hundred participants with
      schizophrenia/schizoaffective disorder completed a reliable and valid headache
      questionnaire. Two clinicians independently classified each headache as migraine,
      tension-type, cervicogenic or other. RESULTS: The 12-month prevalence of headache
      (57%) was higher than the general population (46%) with no evidence of a
      relationship between psychiatric clinical characteristics and presence of
      headache. Prevalence of cervicogenic (5%) and migraine (18%) was comparable to
      the general population. Tension-type (16%) had a lower prevalence and 19% of
      participants experienced other headache. No one with migraine was prescribed
      migraine specific medication; no one with cervicogenic and tension-type received
      best-practice treatment. CONCLUSIONS: Headache is a common complaint in people
      with schizophrenia/schizoaffective disorder with most fitting recognised
      diagnostic criteria for which effective interventions are available. No one in
      this sample was receiving best-practice care for their headache.

PMID- 28747115
TI  - Where pseudo-hallucinations meet dissociation: a cluster analysis.
AB  - OBJECTIVES: The possible link between cognitive areas of perception and
      integration of consciousness was examined using assessments of hallucinations and
      derealisation/depersonalization. METHODS: Sixty-five subjects in three main
      diagnostic groups - posttraumatic stress disorder (PTSD), borderline personality
      disorder (BPD) and schizophrenia - identified by their treating psychiatrist as
      hearing voices were surveyed regarding characteristics of hallucinations,
      derealisation/depersonalization, delusions and childhood/adult trauma. RESULTS: A
      cluster analysis produced two clusters predominantly determined by variables of
      hallucinations measures, childhood sexual abuse and
      derealisation/depersonalization scores. CONCLUSIONS: History of childhood trauma
      and variability in derealisation/depersonalization scores were better predictors
      of external, negative, uncontrollable voices than diagnosis of BPD or PTSD. The
      potential links between dissociative states and pseudo-hallucinations are
      discussed.

PMID- 28747117
TI  - From the President.

PMID- 28747116
TI  - Upcoming RANZCP conferences.

PMID- 28747119
TI  - New College Literature Review: Powers and duties of psychiatrists in Australia
      and New Zealand Mental Health Acts.

PMID- 28747120
TI  - A perspective on the contribution of animal models to the pharmacological
      treatment of posttraumatic stress disorder.
AB  - OBJECTIVES: Posttraumatic stress disorder (PTSD) is a prevalent, chronic,
      disabling disorder that may develop following exposure to a traumatic event. This
      review summarizes currently used animal models of PTSD and their potential role
      in the development of better therapeutics. Heterogeneity is one of the main
      characteristics of PTSD with the consequence that many pharmacological approaches
      are used to relieve symptoms of PTSD. To address the translational properties of
      the animal models, we discuss the types of stressors used, the rodent correlates
      of human PTSD (DSM-5) symptoms, and the efficacy of approved, recommended and off
      label drugs used to treat PTSD in 'PTSD-animals'. CONCLUSIONS: Currently
      available animal models reproduce most PTSD symptoms and are validated by
      existing therapeutics. However, novel therapeutics are needed for this disorder
      as not one drug alleviates all symptoms and many have side effects that lead to
      non-compliance among PTSD patients. The true translational power of animal models
      of PTSD will only be demonstrated when new therapeutics acting through novel
      mechanisms become available for clinical practice.

PMID- 28747121
TI  - Assessment of yoga as an adjuvant treatment for combat-related posttraumatic
      stress disorder.
AB  - OBJECTIVES: This study assessed yoga as an adjuvant strategy for symptoms of
      combat-related posttraumatic stress disorder (PTSD). METHODS: Subjects had
      significant, combat-related PTSD. Control data were collected during an eight
      week waiting period. Trauma-sensitive yoga sessions of 90 minutes duration were
      provided every seven days for eight weeks. Assessments included the PTSD
      checklist (PCL); the Depression, Anxiety and Stress Scale (DASS); the Pittsburgh
      Sleep Quality Index (PSQI); the Adult/Adolescent Sensory Profile (AASP); the SF36
      Quality of Life instrument; and a brief, structured pre-enrolment assessment of
      attitudes towards yoga. Biomarkers were also assessed. RESULTS: Thirty
      participants were recruited, with 28 completing the protocol ( Mage=63.5 years).
      For most variables, there was no significant change in results after the waiting
      period. Comparing measurements obtained immediately prior to the commencement of
      the intervention to those taken after completion of eight yoga sessions,
      significant changes included an increase in the serum dehydroepiandrosterone
      concentration, decreased total PCL score (and all PCL sub-scales), decreases in
      all DASS sub-scale scores and significant improvements in PSQI and SF36 scores.
      No adverse events were reported. CONCLUSIONS: A range of benefits were observed
      after yoga, consistent with the theoretical construct for the long history of
      yoga as a strategy to reduce stress and promote well-being.

PMID- 28747124
TI  - An interview with Prof A McFarlane on PTSD.

PMID- 28747123
TI  - College releases new position statement on mental health legislation and the role
      of psychiatrists.

PMID- 28747125
TI  - New College resources for managing your practice.

PMID- 28747128
TI  - College opposes 10 year moratorium.

PMID- 28747127
TI  - Thoughts on 'Redefining residential rehabilitation in Australia'.

PMID- 28747129
TI  - Talking with Dr Kym Jenkins.

PMID- 28747131
TI  - Association of preoperative breast MRI features with locoregional recurrence
      after breast conservation therapy.
AB  - Background Locoregional recurrence (LRR) following breast conservation therapy
      (BCT) is associated with an increased risk of distant metastasis and death in
      patients with breast cancer. Purpose To investigate whether preoperative breast
      magnetic resonance imaging (MRI) features are associated with the risk of LRR in
      patients undergoing BCT. Material and Methods A total of 3781 women with primary
      invasive breast cancer underwent preoperative MRI and BCT between 2003 and 2013.
      Forty-eight patients who developed LRR comprised the LRR cohort and one-to-one
      matching (age, tumor stage, grade, and axillary nodal status) of each patient to
      a control participant was performed in patients who did not develop recurrence.
      Three readers independently reviewed MR images of the index cancer and the
      presence of multifocal disease was assessed. Chi2 analysis was used to compare
      imaging and clinical features between LRR and control cohorts, with multivariate
      logistic regression analysis used to identify independent features. Results
      Significant differences were found in the proportion of multifocal disease ( P =
      0.001), background parenchymal enhancement level ( P = 0.007), and breast cancer
      molecular subtype ( P = 0.01) between LRR and control cohorts. Multivariate
      analysis showed that multifocal disease (odds ratio [OR] = 11.9; 95% confidence
      interval [CI] = 1.4-102.5; P = 0.02) and human epidermal growth factor receptor 2
      positive subtype (OR = 12.7; 95% CI = 1.3-127.6; P = 0.03) were both
      independently associated with LRR. Conclusion Multifocal disease on preoperative
      breast MRI may indicate an increased risk of LRR in patients treated with BCT.

PMID- 28747130
TI  - Body composition predictors of therapy response in patients with primary
      extremity soft tissue sarcomas.
AB  - Background Recent studies have suggested that the quantity and quality of adipose
      tissue and muscle, assessed on non-contrast computed tomography (CT), may serve
      as imaging biomarkers of survival in patients with and without neoplasms. Purpose
      To assess body composition measures that could serve as predictors of therapy
      response in patients with extremity soft tissue sarcomas treated with radiation
      therapy and surgery. Material and Methods The study was IRB-approved. Sixty
      patients had a history of extremity soft tissue sarcoma and underwent FDG-PET/CT
      prior to radiation therapy and surgical resection. Cross-sectional areas and CT
      attenuation (HU) of abdominal subcutaneous adipose tissue (SAT), visceral adipose
      tissue (VAT), and psoas muscle were assessed on non-contrast CT. Clinical
      information on predictors of tumor recurrence and post-surgical wound infections
      were recorded. Cox proportional hazard models were used to determine longitudinal
      associations between body composition and tumor recurrence/wound infections.
      Results Twenty-three tumor recurrences occurred over a follow-up period of 43 +/-
      35 months. Higher SAT and lower psoas attenuation were associated with tumor
      recurrence which remained significant after adjustment for covariates ( P <=
      0.01). There were 13 post-surgical wound infections. Higher VAT and SAT
      attenuation were associated with post-surgical wound infections ( P < 0.04);
      however, VAT attenuation lost significance after adjustment for covariates.
      Conclusion Abdominal adipose tissue and psoas muscle attenuation assessed on non
      contrast CT may predict tumor recurrence and post-surgical infections in patients
      with extremity soft tissue sarcomas.

PMID- 28747132
TI  - Prostate cancer: in-bore magnetic resonance guided biopsies at active
      surveillance inclusion improve selection of patients for active treatment.
AB  - Background Active surveillance (AS) of low-risk prostate cancer (PCa) is an
      accepted alternative to active treatment. However, the conventional diagnostic
      trans-rectal ultrasound guided biopsies (TRUS-bx) underestimate PCa
      aggressiveness in almost half of the cases, when compared with the surgical
      specimen. Purpose To investigate if additional multi-parametric magnetic
      resonance imaging (mpMRI) of the prostate and MRI-guided in-bore biopsies (MRGB)
      at AS inclusion would improve selection of patients for active treatment.
      Material and Methods All patients enrolled in AS programs at two Danish centers,
      from October 2014 to January 2016, were offered an mpMRI 8-12 weeks after the
      initial diagnostic TRUS-bx. Candidates had low-risk disease (PSA < 10 ng/mL,
      <cT2b, Gleason score [GS] < 7). Prostate lesions were scored on the five-point
      PIRADS scale (version 1 and 2). MRGB were performed on PIRADS 4 or 5 lesions.
      Significant cancer was defined as GS > 6 or GS 6 (3 + 3) lesions with >= 6 mm
      maximal cancer core length (MCCL). Results A total of 78 patients were included
      and in 21 patients a total of 22 PIRADS-score 4 or 5 lesions were detected. MRGB
      pathology revealed that 17 (81%) of these and 22% of the entire AS population
      harbored significant cancers at AS inclusion. In eight (38%) cases, the GS was
      upgraded. Also, nine patients (43%) had GS 6 (3 + 3) foci with MCCL >= 6 mm.
      Conclusion In an AS cohort based on TRUS and TRUS-bx diagnostic strategies,
      supplemental mpMRI and in-bore MRGB were able to efficiently reclassify a
      substantial number of patients as candidates for immediate active treatment.

PMID- 28747133
TI  - Retroperitoneal Laparoscopic Nephrotomy Along the Brodel Line and Tumor
      Enucleation for Complete Intraparenchymal Renal Tumors: A Single Institution
      Experience.
AB  - PURPOSE: To evaluate the feasibility and outcomes of retroperitoneal laparoscopic
      nephrotomy along the Brodel line and tumor enucleation (TE) for complete
      intraparenchymal renal tumors. PATIENTS AND METHODS: We retrospectively analyzed
      the medical charts of patients with complete endophytic tumors and who underwent
      retroperitoneal laparoscopic nephrotomy along the Brodel line and TE between 2012
      and 2015. Perioperative data, surgical technique, pathologic variables,
      complications, functional, and oncologic outcomes were reviewed. RESULTS: Twenty
      one patients (mean age of 50 years; mean body mass index of 25.8 kg/m2) were
      treated with retroperitoneal laparoscopic TE along the Brodel line incision. The
      mean tumor size was 2.0 cm, and the mean RENAL score was 9.4. The main surgical
      outcomes were mean operative time of 94 minutes, mean estimated blood loss of 63
      mL, and mean warm ischemia time of 28.4 minutes. Pathology showed clear renal
      cell carcinoma (n = 16), papillary renal cell carcinoma (n = 4), and reninoma (n
      = 1). No positive margin was found, and no perioperative complication occurred.
      The mean glomerular filtration rate of the affected kidney was 31.5
      mL/minute/1.73 m2 three months after the surgery. In a median follow-up of 20
      months (range of 4-36 months), no evidence of tumor recurrence or metastasis was
      found. CONCLUSION: For patients with complete intraparenchymal renal tumors,
      retroperitoneal laparoscopic parenchyma incision along the Brodel line and TE can
      be safely and effectively performed in centers with significant laparoscopic
      expertise.

PMID- 28747134
TI  - Reporting medical device safety incidents to regulatory authorities: An analysis
      and classification of technology-induced errors.
AB  - The European Union Medical Device Directive 2007/47/EC1 defines software with a
      medical purpose as a medical device. The implementation of health information
      technology suffers from patient safety problems that require effective post
      market surveillance. The purpose of this study was to review, classify and
      discuss the incident data submitted to a nationwide database of the Finnish
      National Competent Authority with other forms of data. We analysed incident
      reports submitted to the authority database by users of electronic health records
      from 2010 to 2015. We identified 138 valid reports. Adverse events associated
      with electronic health record vulnerabilities, clustered around certain error
      types, cause serious harm and occur in all types of healthcare settings. The low
      rate of reported incidents raises questions about not only the challenges
      associated with medical software oversight but also the obstacles for reporting.

PMID- 28747135
TI  - High Burden and Depression Among Late-Stage Idiopathic Parkinson Disease and
      Progressive Supranuclear Palsy Caregivers.
AB  - OBJECTIVES: Caregivers of patients with late-stage idiopathic Parkinson disease
      (IPD) and late-stage progressive supranuclear palsy (PSP) often suffer from
      severe psychological strain themselves. This study investigates the influence of
      the different kind of symptoms in IPD and PSP on the psychological burden of the
      caregivers. METHODS: Twenty patients with late-stage IPD and 20 patients with
      late-stage PSP and their caregivers were investigated. To measure the degree of
      motor, cognitive, and affective impairment of the patients, the instruments
      Subscale III of the Unified Rating Scale for Parkinsonism (UPDRS-III), a
      shortened 24-item version of the Mini-Mental State Examination, and the Geriatric
      Depression Scale (GDS-30) were used. Psychological burden of the caregivers was
      determined by using the Beck Depression Inventory (BDI-II) and the Zarit
      Caregiver Burden Inventory (ZBI). RESULTS: Patients with IPD suffered from a
      higher level of depression (GDS-30: 15.9 vs 10.2, P = .020), whereas patients
      with PSP showed greater motor impairment (UPDRS-III: 38.3 vs 29.9, P = .002).
      Caregivers of both groups reported high psychological burden (ZBI: 36.5 in IPD vs
      42.8 in PSP) and symptoms of a depression (BDI-II: 12.5 in IPD vs 15.1 in PSP).
      No significant influence of motor impairment, cognitive dysfunction, and
      depressive symptoms of the patient on the burden of the caregiver could be found.
      CONCLUSIONS: Psychological strain and depression among caregivers seem to become
      even more relevant in the late stages of IPD and PSP. Further studies will be
      necessary to investigate the specific determining factors in late-stage
      parkinsonian syndromes.

PMID- 28747136
TI  - The Relationship Between Apolipoprotein epsilon4 Carrier Status and Sleep
      Characteristics in Cognitively Normal Older Adults.
AB  - The apolipoprotein (APOE) epsilon4 allele, a well-described genetic risk factor
      for late-onset Alzheimer disease (AD), is associated with sleep disturbances even
      in cognitively normal older adults, although it is not clear whether this
      association is independent of sleep apnea. We sought to extend previous studies
      by examining whether cognitively normal older adults without self-reported sleep
      apnea who carry the APOE epsilon4 allele have altered sleep characteristics
      compared to noncarriers. Data from N = 36 (APOE epsilon4 carriers [n = 9],
      noncarriers [n = 27]) cognitively normal older adults (Clinical Dementia Rating
      [CDR] scale = 0) without self-reported sleep apnea were used for these analyses.
      Participants wore an actigraph for 7 days to determine sleep characteristics. The
      Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were
      used to assess sleep quality and daytime sleepiness, respectively. The APOE
      epsilon4 carriers had a higher number of awakenings compared to the noncarriers (
      P = .02). There was no significant difference in the PSQI global score and the
      ESS; however, the PSQI subcomponent of daily disturbances was significantly
      higher in APOE epsilon4 carriers ( P = .03), indicating increased daytime
      dysfunction is related to disrupted sleep. This study provides evidence that
      individuals who are cognitively normal and genetically at risk of AD may have
      disrupted sleep. These findings are consistent with prior studies and suggest
      that sleep disruption may be present in the presymptomatic stages of AD.

PMID- 28747137
TI  - Modified Pfeffer Questionnaire for Functional Assessment in Parkinson Disease.
AB  - INTRODUCTION: It was proposed to modify the Pfeffer questionnaire (PQ) for
      functional assessment in patients with Parkinson disease (PD). AIM: To determine
      the cutoff score for diagnosis of functional impairment in patients with PD by
      modified PQ (mPQ). METHODS: A total of 110 patients with PD were enrolled into
      the study, and a neuropsychological test battery was performed to assess their
      cognitive status. Regarding functional assessment, the mPQ has been applied, and
      their results were compared to the functional assessment by Informant
      Questionnaire on Cognitive Decline in the Elderly adapted for use in Brazil
      (IQCODE-BR). The statistical analysis was accomplished through receiver operating
      characteristic (ROC) curve with evaluation of the area under the curve,
      sensitivity, and specificity of the new cutoff point. RESULTS: Eighty-nine
      patients with PD were evaluated with a mean age of 63.69 +/- 9.14 years.
      Cognitive status categorization was 28.10% as normal, 44.94% as mild cognitive
      impairment, and 26.96% of patients as dementia associated with PD. The average
      score on PQ was 3.49 +/- 4.79 and on the mPQ 2.56 +/- 3.49. In IQCODE-BR, the
      average score was 6.75 +/- 32.72. The ROC curve for the new cutoff point
      presented 47.4% sensitivity, 88.10% specificity, and 0.757 of area under the
      curve, with a standard deviation of 0.055 (95% confidence interval: 0.650-0.864).
      CONCLUSION: 3.5 is proposed as the cutoff point to define functional impairment
      in patients with PD by mPQ.

PMID- 28747138
TI  - Perspectives on rehabilitation of children with cerebral palsy: exploring a cross
      cultural view of parents from India and Canada using the international
      classification of functioning, disability and health.
AB  - PURPOSE: To explore parents' perspectives on rehabilitation of their child with
      cerebral palsy and their information needs. METHODS: Semistructured interviews
      were conducted with parents of children with CP from India (n = 11) and Canada (n
      = 7). Data were analyzed through an interpretive description approach using the
      International Classification of Functioning, Disability and Health framework.
      RESULTS: Body Structure and Function: Indian parents were more focused on fixing
      body structure and function challenges, and independent walking, than Canadian
      parents. Activity and Participation: All Canadian children were actively involved
      in school and fun activities in the community. Due to lack of accessible
      services, Indian children had less school and community participation.
      Environmental factors: accessible communities, occupational therapy services and
      greater use of assistive devices enabled Canadian children. Social and cultural
      beliefs, lack of access to services and inaccessible communities were the
      barriers experienced by Indian parents. Information needs: both groups needed
      information to make their child more functional. CONCLUSION: Canadian parents
      experience a more enabling environment and express a more social view of their
      child's health, suggesting both education on the International Classification of
      Functioning, Disability and Health principles and services are needed to better
      enable and empower Indian parents. There remains a need for healthcare
      professionals and services in both countries to be more family-centered.
      Implications for rehabilitation To help parents in rehabilitating their children
      with cerebral palsy (CP), in India, there is a need to (1) incorporate ICF
      education into medical curricula and clinical practice; (2) increase the
      availability of skilled healthcare professionals and centers; (3) make
      infrastructural and policy reforms to make the society more accessible for the
      disabled children. Education, counseling and awareness about CP might help both
      groups of parents, society, and HCPs to change their beliefs and attitudes
      regarding CP and its rehabilitation. Both countries would benefit from user
      friendly and transparent policies. This will help parents to become more aware of
      them and use them in the rehabilitation process.

PMID- 28747139
TI  - A monoclonal antibody against CD86 and its protection in a murine lupus nephritis
      model of chronic graft-versus-host disease.
AB  - CONTEXT: Lupus nephritis is the most common complication that causes the death of
      systemic lupus erythematosus patients. CD28/CTLA4 and their ligands CD80 or CD86
      costimulatory pathway play a pivotal role in autoimmune disease and organ
      transplantation. OBJECTIVES: We generated a monoclonal antibody (clone 1D1)
      against human CD86 (1D1) that could recognize both human and mouse CD86, and
      blocked the CD86/CD28 costimulatory pathway with our mAb on a murine lupus
      nephritis model induced with chronic graft-versus-host disease (cGVHD). MATERIALS
      AND METHODS: Experimental lupus nephritis mice were induced with cGVHD, and
      splenocyte population were analyzed by flow cytometry. Autoantibodies and
      proteinuria were detected to evaluate the severity of lupus nephritis. The change
      of histopathology was observed by microscopy, fluorescence microscopy and
      electron microscopy. RESULTS: we successfully generated a monoclonal antibody
      against human CD86(1D1). 1D1 mAb could recognize not only human CD86, but also
      mouse CD86. 1D1 was applied to the cGVHD-induced experimental lupus nephritis
      model, and our study found the production of ANA and anti-dsDNA in the 1D1
      treated group was lower than those in IgG-treated group after four weeks. The
      pathological injure of kidney in the 1D1-treated group was lighten than that in
      IgG-treated group. DISCUSSION AND CONCLUSIONS: Our data showed that blockade of
      CD86/CD28 with 1D1 induced a significant remission of proteinuria, production of
      autoantibodies, immune complex deposition and renal parenchyma lesions in
      experimental mice. Anti-CD86 Abs might be a potential method for immune therapy
      in autoimmune diseases and transplantation.

PMID- 28747141
TI  - Biochemical and pathological changes in the male rat kidney and bladder following
      exposure to continuous 900-MHz electromagnetic field on postnatal days 22
      59<sup/>.
AB  - PURPOSE: To investigate the effect on male rat kidney and bladder tissues of
      exposure to 900-megahertz (MHz) electromagnetic field (EMF) applied on postnatal
      days 22-59, inclusive. MATERIALS AND METHODS: Twenty-four male Sprague Dawley
      rats, aged 21 days, were used. These were divided equally into one of three
      groups, control (CG), sham (SG) or EMF (EMFG). CG was not exposed to any
      procedure. SG rats were kept inside a cage, without being exposed to the effect
      of EMF, for 1 h a day on postnatal days 22-59, inclusive. EMFG rats were exposed
      to continuous 900-MHz EMF for 1 h a day under the same conditions as those for
      the SG rats. Rats were sacrificed on postnatal day 60, and the kidney and bladder
      tissues were removed. Tissues were stained with hematoxylin and eosin (H&E) and
      Masson trichrome for histomorphological evaluation. The TUNEL method was used to
      assess apoptosis. Transmission electron microscopy (TEM) was also used for the
      kidney tissue. Oxidant/antioxidant parameters were studied in terms of
      biochemical values. RESULTS: The findings showed that tissue malondialdehyde
      increased in EMFG compared to CG and SG in both kidney (p = 0.004 and p = 0.004,
      respectively) and bladder tissue (p = 0.004, p = 0.006, respectively), while
      catalase and glutathione levels decreased compared to CG (p = 0.004; p = 0.004,
      respectively) and SG (p = 0.004; p = 0.004, respectively). In the EMF group,
      pathologies such as dilatation and vacuolization in the distal and proximal
      tubules, degeneration in glomeruli and an increase in cells tending to apoptosis
      were observed in kidney tissue. In bladder tissue, degeneration in the
      transitional epithelium and stromal irregularity and an increase in cells tending
      to apoptosis were observed in EMFG. Additionally, EMFG samples exhibited
      glomerular capillary degeneration with capillary basement membranes under TEM.
      CONCLUSIONS: We conclude that continuous exposure to the effect of 900-MHz EMF
      for 1 h a day on postnatal days 22-59, inclusive, causes an increase in oxidative
      stress and various pathological changes in male rat kidney and bladder tissues.

PMID- 28747140
TI  - Mitochondrial assembly receptor expression is an independent prognosticator for
      patients with oral tongue squamous cell carcinoma.
AB  - INTRODUCTION: Recent evidence suggests that the local renin-angiotensin system
      has been implicated in various malignancies. The mitochondrial assembly receptor
      is a newly identified receptor for angiotensin peptides, angiotensin-(1-7), and
      has an important role in the renin-angiotensin system. However, the role of the
      mitochondrial assembly receptor in the prognosis of cancer patients remains
      unclear. The aim of this study was to evaluate the significance of mitochondrial
      assembly receptor signaling in the prognosis of oral tongue squamous cell
      carcinoma. METHODS: Mitochondrial assembly receptor immunohistochemistry was
      examined in 151 oral tongue squamous cell carcinoma patients and was correlated
      with treatment outcome. The functional relevance of the mitochondrial assembly
      receptor in oral tongue squamous cell carcinoma cell lines was evaluated by 3
      (4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide reduction and
      bromodeoxyuridine incorporation assays. RESULTS: Mitochondrial assembly receptor
      overexpression was significantly correlated with early pathological T
      classification ( p=0.029) and the absence of extracapsular spread ( p=0.039).
      Univariate analyses demonstrated that mitochondrial assembly receptor
      overexpression was significantly associated with superior overall survival (
      p=0.012). In multivariate comparison, mitochondrial assembly receptor
      overexpression remained independently associated with superior overall survival (
      p=0.008, hazard ratio=1.862). In vitro, angiotensin-(1-7) suppressed the cell
      growth in oral tongue squamous cell carcinoma cells, and this response was
      reversed by the mitochondrial assembly receptor antagonist, A779. CONCLUSION:
      Mitochondrial assembly receptor expression is independently associated with the
      prognosis of oral tongue squamous cell carcinoma patients. These findings suggest
      that mitochondrial assembly receptor signaling may be a promising novel target
      for oral tongue squamous cell carcinoma.

PMID- 28747142
TI  - Development of the First World Health Organization Lentiviral Vector Standard:
      Toward the Production Control and Standardization of Lentivirus-Based Gene
      Therapy Products.
AB  - Gene therapy is a rapidly evolving field. So far, there have been >2,400 gene
      therapy products in clinical trials and four products on the market. A
      prerequisite for producing gene therapy products is ensuring their quality and
      safety. This requires appropriately controlled and standardized production and
      testing procedures that result in consistent safety and efficacy. Assuring the
      quality and safety of lentivirus-based gene therapy products in particular
      presents a great challenge because they are cell-based multigene products that
      include viral and therapeutic proteins as well as modified cells. In addition to
      the continuous refinement of a product, changes in production sites and
      manufacturing processes have become more and more common, posing challenges to
      developers regarding reproducibility and comparability of results. This paper
      discusses the concept of developing a first World Health Organization
      International Standard, suitable for the standardization of assays and enabling
      comparison of cross-trial and cross-manufacturing results for this important
      vector platform. The standard will be expected to optimize the development of
      gene therapy medicinal products, which is especially important, given the usually
      orphan nature of the diseases to be treated, naturally hampering reproducibility
      and comparability of results.

PMID- 28747143
TI  - The relationship between physical activity, fitness, physical complaints and BMI
      in German adults - results of a longitudinal study.
AB  - OBJECTIVES: This study's aims were to describe the development of physical
      activity, physical fitness (PF), subjective (physical complaints (PC)) and
      objective (Body mass index (BMI)) health measures and to examine the relationship
      between the development trajectories. In addition, the study also aimed to assess
      the influence of sociodemographic determinants (age, sex, socioeconomic status
      (SES)) in German adults over a period of 18 years. METHODS: The longitudinal
      study population comprises of 721 men and women, aged 33-76 years over the study
      period. There was self-report of physical activity and PC and testing of physical
      fitness and BMI in each study year (1992, 1997, 2002 and 2010). Latent growth
      curve models were used to analyse the development. RESULTS: Physical activity
      slightly increased while fitness, PC and BMI worsened over the course of 18
      years. Sex, age and SES play important roles concerning physical activity,
      fitness and health. Several integrative associations could be detected between
      physical activity, fitness, PC and BMI as well as their trajectories. In
      particular, high initial levels of physical activity and fitness protect from
      high PC and BMI.The slope of physical activity was not significantly associated
      with slopes of fitness, PC and BMI. However, increase of fitness resulted in
      decrease of PC. CONCLUSIONS: A general positive development regarding the amount
      of physical activity could be detected. However, if it is only an unsystematic
      increase of physical activity, this is not in itself enough to achieve health
      benefits. The strengthening of fitness should be focused when increasing physical
      activity, since only then a health benefit is possible.

PMID- 28747144
TI  - ABCG2 c.421C>A Is Associated with Outcomes after Severe Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) is a leading cause of death with no pharmacological
      treatments that improve outcomes. Transporter proteins participate in TBI
      recovery by maintaining the central nervous system (CNS) biochemical milieu.
      Genetic variations in transporters that alter expression and/or function have
      been associated with TBI outcomes. The ATP-binding cassette transporter, ABCG2,
      is a uric acid (UA) transporter that effluxes UA from cells in the CNS and is
      responsible for systemic UA clearance. Uric acid is a CNS antioxidant and/or a
      biomarker that might support TBI recovery. Our objective was to investigate the
      impact of ABCG2 SNP: c.421C>A on TBI outcomes. Two cohorts (discovery [N = 270]
      and replication [N = 166]) were genotyped for ABCG2 c.421C>A. Glasgow Outcome
      Scale (GOS) scores were collected at 3, 6, 12, and 24 months post-injury and
      compared with mixed-effects multiple ordinal regression controlled for time post
      injury, age, sex, time, post-injury imaging determined hemorrhage types, and
      Glasgow Coma Scale score. Variant alleles (genotype) were associated with better
      GOS scores (p = 0.01 [discovery] and p = 0.02 [replication]), whereas
      genotype*age interaction was associated with worse GOS scores (p = 0.03
      [discovery] and p = 0.01 [replication]). Reversed coefficient directionality
      suggests variant allele(s) are protective up to approximately age 34 years.
      Overall, variant alleles at ABCG2 c.421C>A associate with better GOS scores post
      injury in two independently sampled cohorts. This finding is mitigated by
      increasing subject age. This suggests that ABCG2 might have an age-dependent
      effect on TBI recovery and should be explored in future mechanistic studies.

PMID- 28747145
TI  - Human papillomavirus infection among male clients of female sex workers
      soliciting sex in brothels in Peru.
AB  - The prevalence of high-risk human papillomavirus (HR-HPV) has been reported to be
      three times higher in female sex workers (FSWs) in Callao, Peru than in the
      general population of women in Peru. Prevalence of HR-HPV among male clients has
      not yet been reported. A total of 150 men soliciting intercourse in sex work
      venues submitted questionnaires, samples for sexually transmitted infection (STI)
      testing, and self-collected penile samples prior to and following intercourse for
      HPV genotyping. We identified variables associated with pre-coital HR-HPV, and
      compared HR-HPV detection pre- and post-coitus. Prior to intercourse, HR-HPV
      prevalence was 41.9%. Married clients were less likely than unmarried clients to
      have HR-HPV detected ( p = 0.03). While post-coital HR-HPV prevalence was higher
      (47.6%), the difference was not statistically significant. However, there was a
      significant increase in the mean number of HR-HPV DNA strains detected before
      (0.75) and after (0.94) intercourse ( p = 0.02). No cases of gonorrhoea or
      syphilis and six (4.1%) cases of chlamydial infection were detected. Despite low
      prevalence of other STIs, male clients had a high HR-HPV prevalence. The increase
      in detection of HR-HPV following intercourse demonstrates a potential for
      transmission of HR-HPV despite high self-reported condom use.

PMID- 28747147
TI  - Dimethyl fumarate for patients with neuromyelitis optica spectrum disorder.

PMID- 28747146
TI  - Age-Dependent Subchondral Bone Remodeling and Cartilage Repair in a Minipig
      Defect Model.
AB  - After cartilage injury and repair, the subchondral bone plate remodels. Skeletal
      maturity likely impacts both bone remodeling and inherent cartilage repair
      capacity. The objective of this study was to evaluate subchondral bone remodeling
      as a function of injury type, repair scenario, and skeletal maturity in a Yucatan
      minipig model. Cartilage defects (4 mm) were created bilaterally in the trochlear
      groove. Treatment conditions included a full thickness chondral defect (full
      chondral defect, n = 3 adult/3 juvenile), a partial thickness (~50%) chondral
      defect (PCD, n = 3/3), and FCD treated with microfracture (MFX, n = 3/3). At 6
      weeks postoperatively, osteochondral samples containing the lesion site were
      imaged by micro-computed tomography (CT) and analyzed by histology and
      immunohistochemistry. Via micro-CT, FCD and MFX groups showed increased bone loss
      in juveniles compared with adults. Quantification of histology using the ICRS II
      scoring system showed equal overall assessment for the FCD groups and better
      overall assessment in juvenile animals treated with MFX compared with adults. All
      FCD and MFX groups were inferior to control samples. For the PCD injury, both age
      groups had values close to the control values. For the FCD groups, there were
      greater alterations in the subchondral bone in juveniles compared with adults.
      Staining for collagen II showed more intense signals in juvenile FCD and MFX
      groups compared with adults. This large animal study of cartilage repair shows
      the significant impact of skeletal maturity on the propensity of subchondral bone
      to remodel as a result of chondral injury. This will improve selection criteria
      for animal models for studying cartilage injury, repair, and treatment.

PMID- 28747148
TI  - Letter to the editor.

PMID- 28747150
TI  - Reply to letter to the editor: Dimethyl fumarate for patients with neuromyelitis
      optica spectrum disorder by Pitarokoili and Gold.

PMID- 28747149
TI  - Public Health Interventions: School Nurse Practice Stories.
AB  - This study describes and analyzes school nurses' (SN) experiences with
      understanding and using public health interventions from the Public Health
      Intervention Wheel. The Wheel offers a model for naming interventions provided by
      SNs from a public health perspective. Research teams from academic and SN
      practice settings conducted six focus groups with school nurses from Minnesota.
      Participants were asked to share experiences through telling stories from their
      practice that represented a specific wedge of the Wheel. Researchers organized
      data by intervention; often stories represented more than one intervention.
      Stories represented all levels of practice. This study highlights important
      contributions of school nurses to promote the health of school populations
      through the use of Wheel interventions. The integration of Wheel interventions in
      the application of the Framework for 21st-Century School Nursing PracticeTM
      provides SNs with a language to document and communicate their expert
      professional practice.

PMID- 28747151
TI  - Comparative analysis of targeted long read sequencing approaches for
      characterization of a plant's immune receptor repertoire.
AB  - BACKGROUND: The Oxford Nanopore Technologies MinIONTM sequencer is a small,
      portable, low cost device that is accessible to labs of all sizes and attractive
      for in-the-field sequencing experiments. Selective breeding of crops has led to a
      reduction in genetic diversity, and wild relatives are a key source of new
      genetic resistance to pathogens, usually via NLR immune receptor-encoding genes.
      Recent studies have demonstrated how crop NLR repertoires can be targeted for
      sequencing on Illumina or PacBio (RenSeq) and the specific gene conveying
      pathogen resistance identified. RESULTS: Sequence yields per MinION run are lower
      than Illumina, making targeted resequencing an efficient approach. While MinION
      generates long reads similar to PacBio it doesn't generate the highly accurate
      multipass consensus reads, which presents downstream bioinformatics challenges.
      Here we demonstrate how MinION data can be used for RenSeq achieving similar
      results to the PacBio and how novel NLR gene fusions can be identified via a
      Nanopore RenSeq pipeline. CONCLUSION: The described library preparation and
      bioinformatics methods should be applicable to other gene families or any
      targeted long DNA fragment nanopore sequencing project.

PMID- 28747152
TI  - Associations between male infertility and ancestry in South Americans: a case
      control study.
AB  - BACKGROUND: Infertility affects 15% of human couples, with men being responsible
      in approximately 50% of cases.Moreover, the aetiology of male factor infertility
      is poorly understood. The majority of male factor infertility remainsidiopathic
      and potentially genetic in origin. The association of the Y chromosome and
      mitochondrial haplogroupswith male infertility has been previously reported. This
      association differs between studied populations and theirgeographical
      distributions. These effects have been only rarely analysed in mixed populations,
      such as SouthAmericans. METHODS: In this study, we analysed the contributions of
      the Y chromosome and mitochondrial haplogroups tomale infertility in a mixed
      population. A case control study was conducted. Regular PCR and high
      resolutionmelting-real-time PCR were performed to type haplogroups from fertile
      and infertile men.The sperm parameters from infertile men were compared in each
      haplogroup by logistic regression analysis and ANOVA. RESULTS: The genotyping
      confirmed the known admixture characteristic of the Uruguayan population. The
      Europeanpaternal contribution was higher than the maternal contribution in both
      fertile and infertile men. Neither maternal nor paternal ancestry presented
      differences between the cases and controls. Men belonging to the Y
      chromosomehaplogroup F(xK) more frequently presented with an abnormal sperm
      morphology than men from other haplogroups.The sperm parameters were not
      associated with the mitochondrial haplogroups. CONCLUSIONS: The data presented in
      this study showed an association between male infertility and ancestry in
      theUruguayan population. Specifically, abnormal sperm morphology was associated
      with the Y chromosome haplogroup F(xK). Since the Y chromosome lacks
      recombination, these data suggest that some genes that determine sperm morphology
      might be inherited in blocks with the region that determines specific
      haplogroups. However, the possible association between the Y chromosome
      haplogroup F(xK) and sperm morphology requires further confirmatory testing. Data
      linking infertility with ancestry are needed to establish the possible causes of
      infertility and define male populations susceptible to infertility. Whether the
      admixed characteristics of the Uruguayan population exert any pressure on male
      fertility potential must be further investigated.

PMID- 28747153
TI  - Temporal and spatial analysis of psittacosis in association with poultry farming
      in the Netherlands, 2000-2015.
AB  - BACKGROUND: Human psittacosis is a highly under diagnosed zoonotic disease,
      commonly linked to psittacine birds. Psittacosis in birds, also known as avian
      chlamydiosis, is endemic in poultry, but the risk for people living close to
      poultry farms is unknown. Therefore, our study aimed to explore the temporal and
      spatial patterns of human psittacosis infections and identify possible
      associations with poultry farming in the Netherlands. METHODS: We analysed data
      on 700 human cases of psittacosis notified between 01-01-2000 and 01-09-2015.
      First, we studied the temporal behaviour of psittacosis notifications by applying
      wavelet analysis. Then, to identify possible spatial patterns, we applied spatial
      cluster analysis. Finally, we investigated the possible spatial association
      between psittacosis notifications and data on the Dutch poultry sector at
      municipality level using a multivariable model. RESULTS: We found a large spatial
      cluster that covered a highly poultry-dense area but additional clusters were
      found in areas that had a low poultry density. There were marked geographical
      differences in the awareness of psittacosis and the amount and the type of
      laboratory diagnostics used for psittacosis, making it difficult to draw
      conclusions about the correlation between the large cluster and poultry density.
      The multivariable model showed that the presence of chicken processing plants and
      slaughter duck farms in a municipality was associated with a higher rate of human
      psittacosis notifications. The significance of the associations was influenced by
      the inclusion or exclusion of farm density in the model. CONCLUSIONS: Our
      temporal and spatial analyses showed weak associations between poultry-related
      variables and psittacosis notifications. Because of the low number of psittacosis
      notifications available for analysis, the power of our analysis was relative low.
      Because of the exploratory nature of this research, the associations found cannot
      be interpreted as evidence for airborne transmission of psittacosis from poultry
      to the general population. Further research is needed to determine the prevalence
      of C. psittaci in Dutch poultry. Also, efforts to promote PCR-based testing for
      C. psittaci and genotyping for source tracing are important to reduce the
      diagnostic deficit, and to provide better estimates of the human psittacosis
      burden, and the possible role of poultry.

PMID- 28747154
TI  - The interplay between individual social behavior and clinical symptoms in small
      clustered groups.
AB  - BACKGROUND: Mixing patterns of human populations play a crucial role in shaping
      the spreading paths of infectious diseases. The diffusion of mobile and wearable
      devices able to record close proximity interactions represents a great
      opportunity for gathering detailed data on social interactions and mixing
      patterns in human populations. The aim of this study is to investigate how social
      interactions are affected by the onset of symptomatic conditions and to what
      extent the heterogeneity in human behavior can reflect a different risk of
      infection. METHODS: We study the relation between individuals' social behavior
      and the onset of different symptoms, by making use of data collected in 2009
      among students sharing a dormitory in a North America university campus. The
      dataset combines Bluetooth proximity records between study participants with self
      reported daily records on their health state. Specifically, we investigate
      whether individuals' social activity significantly changes during different
      symptomatic conditions, including those defining Influenza-like illness, and
      highlight to what extent possible heterogeneities in social behaviors among
      individuals with similar age and daily routines may be responsible for a
      different risk of infection for influenza. RESULTS: Our results suggest that
      symptoms associated with Influenza-like illness can be responsible of a reduction
      of about 40% in the average duration of contacts and of 30% in the daily time
      spent in social interactions, possibly driven by the onset of fever. However,
      differences in the number of daily contacts were found to be not statistically
      significant. In addition, we found that individuals who experienced clinical
      influenza during the study period were characterized by a significantly higher
      social activity. In particular, both the number of person-to-person contacts and
      the time spent in social interactions emerged as significant risk factors for
      influenza infection. CONCLUSIONS: Our findings highlight that Influenza-like
      illness can remarkably reduce the social activity of individuals and strengthen
      the idea that the heterogeneity in social habits among individuals can
      significantly contribute in shaping differences among the individuals' risk of
      infection.

PMID- 28747155
TI  - Indole 3-acetic acid, indoxyl sulfate and paracresyl-sulfate do not influence
      anemia parameters in hemodialysis patients.
AB  - BACKGROUND: The main reason for anemia in renal failure patients is the
      insufficient erythropoietin production by the kidneys. Beside erythropoietin
      deficiency, in vitro studies have incriminated uremic toxins in the
      pathophysiology of anemia but clinical data are sparse. In order to assess if
      indole 3-acetic acid (IAA), indoxyl sulfate (IS), and paracresyl sulfate (PCS) 
      three protein bound uremic toxins- are clinically implicated in end-stage renal
      disease anemia we studied the correlation between IAA, IS and PCS plasmatic
      concentrations with hemoglobin and Erythropoietin Stimulating Agents (ESA) use in
      hemodialysis patients. METHODS: Between June and July 2014, we conducted an
      observational cross sectional study in two hemodialysis center. Three statistical
      approaches were conducted. First, we compared patients treated with ESA and those
      not treated. Second, we performed linear regression models between IAA, IS, and
      PCS plasma concentrations and hemoglobin, the ESA dose over hemoglobin ratio
      (ESA/Hemoglobin) or the ESA resistance index (ERI). Third, we used a polytomous
      logistic regression model to compare groups of patients with no/low/high ESA dose
      and low/high hemoglobin statuses. RESULTS: Overall, 240 patients were included in
      the study. Mean age +/- SD was 67.6 +/- 16.0 years, 55.4% were men and 42.5% had
      diabetes mellitus. When compared with ESA treated patients, patients with no ESA
      had higher hemoglobin (mean 11.4 +/- 1.1 versus 10.6 +/- 1.2 g/dL; p <0.001),
      higher transferrin saturation (TSAT, 31.1 +/- 16.3% versus 23.1 +/- 11.5%; p <
      0.001), less frequently an IV iron prescription (52.1 versus 65.7%, p = 0.04) and
      were more frequently treated with hemodiafiltration (53.5 versus 36.7%). In
      univariate analysis, IAA, IS or PCS plasma concentrations did not differ between
      the two groups. In the linear model, IAA plasma concentration was not associated
      with hemoglobin, but was negatively associated with ESA/Hb (p = 0.02; R = 0.18)
      and with the ERI (p = 0.03; R = 0.17). IS was associated with none of the three
      anemia parameters. PCS was positively associated with hemoglobin (p = 0.03; R =
      0.14), but negatively with ESA/Hb (p = 0.03; R = 0.17) and the ERI (p = 0.02; R =
      0.19). In multivariate analysis, the association of IAA concentration with ESA/Hb
      or ERI was not statistically significant, neither was the association of PCS with
      ESA/Hb or ERI. Identically, in the subgroup of 76 patients with no inflammation
      (CRP <5 mg/L) and no iron deficiency (TSAT >20%) linear regression between IAA,
      IS or PCS and any anemia parameter did not reach significance. In the third
      model, univariate analysis showed no intergroup significant differences for IAA
      and IS. Regarding PCS, the Low Hb/High ESA group had lower concentrations.
      However, when we compared PCS with the other significant characteristics of the
      five groups to the Low Hb/high ESA (our reference group), the polytomous logistic
      regression model didn't show any significant difference for PCS. CONCLUSIONS: In
      our study, using three different statistical models, we were unable to show any
      correlation between IAA, IS and PCS plasmatic concentrations and any anemia
      parameter in hemodialysis patients. Indolic uremic toxins and PCS have no or a
      very low effect on anemia parameters.

PMID- 28747156
TI  - Influence of chemotherapeutic drug-related gene polymorphisms on toxicity and
      survival of early breast cancer patients receiving adjuvant chemotherapy.
AB  - BACKGROUND: We investigated whether GSTT1 ("null" allele), GSTM1 ("null"allele),
      GSTP1 (A313G), RFC1 (G80A), MTHFR (C677T), TS (2R/3R) polymorphisms were
      associated with toxicity and survival in patients with early breast cancer (EBC)
      treated with adjuvant chemotherapy (CT). METHODS: This prospective trial included
      patients with stage I-III BC subjected to CT with CMF or FEC regimens. PCR-RFLP
      was performed for MTHFR, RFC1 and GSTP1, while PCR for TS, GSTT1 and GSTM1 genes.
      RESULTS: Among the 244 patients consecutively enrolled, 48.7% were treated with
      FEC and 51.3% with CMF. Patients with TS2R/3R genotype showed less frequently
      severe neutropenia (G3/G4) than those with TS2R/2R and 3R/3R genotype (p =
      0.038). Patients with MTHFRCT genotype had a higher probability of developing
      severe neutropenia than those with MTHFR CC genotype (p = 0.043). Patients with
      RFC1GG or GSTT1-null genotype or their combination (GSTT1-null/RFC1GG) were
      significantly associated with a shorter disease free survival (DFS) (p = 0.009, p
      = 0.053, p = 0.003, respectively) and overall survival (OS) (p = 0.036, p =
      0.015, p = 0.005, respectively). Multivariate analysis confirmed the association
      of RFC1GG genotype with a shorter DFS (p = 0.018) and of GSTT1-null genotype of a
      worse OS (p = 0.003), as well as for the combined genotypes GSTT1-null/RFC1GG,
      (DFS: p = 0.004 and OS: p = 0.003). CONCLUSIONS: Our data suggest that TS2R/2R
      and 3R/3R or MTHFR CT genotypes have a potential role in identifying patients
      with greater risk of toxicity to CMF/FEC and that RFC1 GG and GSTT1-null
      genotypes alone or in combination could be important markers in predicting
      clinical outcome in EBC patients.

PMID- 28747157
TI  - Oral health literacy and oral health outcomes in an adult population in Brazil.
AB  - BACKGROUND: To investigate the association between critical and communicative
      oral health literacy (OHL) and oral health outcomes (status, oral health-related
      quality of life and practices) in adults. METHODS: This cross-sectional study
      examined a household probability sample of 248 adults, representing 149,635
      residents (20-64 years old) in Piracicaba-SP, Brazil. Clinical oral health and
      socioeconomic and demographic data, as well as data on oral health-related
      quality of life (OHIP-14) and health practices were collected. The oral
      examinations were carried out in the participants' homes, using the World Health
      Organization criteria for oral diseases. The critical and communicative OHL
      instrument was the primary independent variable, and it was measured using five
      Likert items that were dichotomized as 'high' ('agree' and 'strongly agree'
      responses for the 5 items) and 'low' OHL. Binary and multinomial logistic
      regressions were performed on each outcome (oral health status and practices),
      controlling for age, sex and socioeconomic status (SES). RESULTS: Approximately
      71.5% presented low OHL. When adjusted for age and sex (first model) low OHL was
      associated with untreated caries (Odds Ratio = 1.92, 95% Confidence Interval =
      1.07-3.45), tooth brushing <3 times a day (OR = 2.00, 1.11-3.62) and irregular
      tooth flossing (OR = 2.17, 1.24-3.80). After SES inclusion in the first model,
      significant associations were found for low OHL when the outcomes were: presence
      of biofilm (OR = 1.83, 1.08-3.33), dental care for emergency only (OR = 2.24,
      1.24-4.04) and prevalence of oral health impact on quality of life (OR = 2.06,
      1.15-3.69). CONCLUSION: Adjusting for age, sex and SES, OHL is related to a risk
      factor (biofilm) and a consequence of poor oral health (emergency dental visits)
      and can interfere with the impact of oral diseases on quality of life. As low OHL
      can be modified, the results support oral health promotion strategies directed at
      improving critical and communicative oral health literacy in adult populations.

PMID- 28747158
TI  - Characteristics of disability in activity of daily living in elderly people
      associated with locomotive disorders.
AB  - BACKGROUND: Ageing is associated with a decline of motor function and ability to
      perform daily activities. Locomotive disorders are one of the major disorders
      resulting in adverse health condition in elderly people. Concept of Locomotive
      syndrome (LoS) was proposed to tackle the problems and prolong healthy life
      expectancy of people with locomotive disorders. To develop intervention strategy
      for LoS it is mandatory to investigate impairments, functional disabilities which
      people with locomotive disorder experience and to examine relationships among
      these parameters. For this purpose we have developed Geriatric Locomotive
      Function Scale-25 (GLFS-25). Though several physical performance tests were
      reported for identification or monitoring the severity of LoS, there are few
      studies reported on characteristics of disability which people with locomotive
      disorders experience. The aim of this study was to report the characteristics of
      ADL disabilities in elderly people with locomotive disorders in terms of numbers
      and degree of activity limitations. METHODS: We organized a cohort study and
      recruited 314 participants aged 65 years and over from five orthopedic clinics or
      nursing care facilities. This was a cross-sectional study to use the baseline
      data of such cohort. ADL disabilities were assessed using GLFS-25 scale arranging
      the GLFS-25 scores in ordinal levels using "R language" program. Numbers and
      degrees of activity limitations were determined and compared among the levels.
      Frequency of limitation in activities regarding social activity, housework,
      locomotion, mobility and self-care was compared among across the disability
      level. RESULTS: The GLFS-25 score was mathematically categorized into 7 levels.
      The number of activity limitations and the degrees of each activity limitation
      were significantly greater in high GLFS-25 levels than in low levels.
      Difficulties in mobility appeared in less severe level, difficulties in domestic
      and social life appeared in moderately severe level, and difficulties in self
      care appeared in advanced level. CONCLUSIONS: High GLFS-25 score represented high
      degree of disability on ADLs. Concordant increase of numbers of activity
      limitation and severity progression in activity limitation may contribute to
      progression of disability. Activity limitation may occur in the following order:
      sports activity, walking, transferring, and self-care.

PMID- 28747159
TI  - A case report of CT-diagnosed renal infarct secondary to syphilitic aortitis.
AB  - BACKGROUND: Even though reported cases of syphilis have been increasing, cases of
      tertiary syphilis remain extremely rare. The majority of our knowledge with
      regard to complications of syphilis such as aortitis was acquired before the
      advent of relatively modern technologies such as CT, MRI and PET. This case
      report presents a rare case of syphilitic aortitis associated with a renal
      infarct caused by a peripheral arterial embolism diagnosed by CT. CASE
      PRESENTATION: We present a young man with sudden abdominal pain and flank
      tenderness without fever. Blood tests showed acute kidney failure. Computed
      tomography showed a right renal infarct and a non-circular thickening of the
      descending thoracic aortic wall with intra-luminal thrombus. Serology confirmed
      the diagnosis of syphilis. Treatment with anticoagulant and penicillin resulted
      in a good outcome. Follow-up PET-MRI showed resolution of the thrombus with a
      metabolically inactive atheromatous plaque. CONCLUSION: Technologies, such as CT,
      PET-CT and PET-MRI, that were not present during the pre-antibiotic era, can
      provide new insights into rare presentations of tertiary syphilis such as
      aortitis. These imaging modalities show promise for early radiological diagnosis
      of aortitis in syphilis and may be useful for determining the response to
      treatment in specific cases.

PMID- 28747160
TI  - Adverse events in women and children who have received intrapartum antibiotic
      prophylaxis treatment: a systematic review.
AB  - BACKGROUND: Adverse events from intrapartum antibiotic prophylaxis (IAP) are
      poorly documented yet essential to inform clinical practice for neonatal group B
      Streptococcus (GBS) disease prevention. In this systematic review, we appraised
      and synthesised the evidence on the adverse events of IAP in the mother and/or
      her child. METHODS: We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed
      Citations, EMBASE, Cochrane, and Science Citation Index from date of inception
      until October 16th 2016. Reference lists of included studies and relevant
      systematic reviews were hand-searched. We included primary studies in English
      that reported any adverse events from intrapartum antibiotics for any
      prophylactic purpose compared to controls. The search was not restricted to
      prophylaxis for GBS but excluded women with symptoms of infection or undergoing
      caesarean section. Two reviewers assessed the methodological quality of studies,
      using the Cochrane Risk of Bias tool, and the Risk of Bias Assessment Tool for
      Nonrandomised Studies. Results were synthesised narratively and displayed in text
      and tables. RESULTS: From 2364 unique records, 30 studies were included. Despite
      a wide range of adverse events reported in 17 observational studies and 13
      randomised controlled trials (RCTs), the evidence was inconsistent and at high
      risk of bias. Only one RCT investigated the long-term effects of IAP reporting
      potentially serious outcomes such as cerebral palsy; however, it had limited
      applicability and unclear biological plausibility. Seven observational studies
      showed that IAP for maternal GBS colonisation alters the infant microbiome.
      However, study populations were not followed through to clinical outcomes,
      therefore clinical significance is unknown. There was also observational evidence
      for increased antimicrobial resistance, however studies were at high or unclear
      risk of bias. CONCLUSIONS: The evidence base to determine the frequency of
      adverse events from intrapartum antibiotic prophylaxis for neonatal GBS disease
      prevention is limited. As RCTs may not be possible, large, better quality, and
      longitudinal observational studies across countries with widespread IAP could
      fill this gap. TRIAL REGISTRATION: CRD42016037195 .

PMID- 28747161
TI  - Factors associated with perinatal mortality among public health deliveries in
      Addis Ababa, Ethiopia, an unmatched case control study.
AB  - BACKGROUND: perinatal mortality is the sum of still birth (fetal death) and early
      neonatal death (ENND) i.e. death of live newborn before the age of 7 completed
      days. Perinatal mortality accounts three fourth of the deaths of the neonatal
      period and is one of the major challenges for under-five mortality. Therefore
      this study was conducted to better understand the common and avoidable factors
      that affect perinatal mortality in Addis Ababa, Ethiopia. METHODS: An unmatched
      case control study design using secondary data as a source of information was
      conducted. Cases were still births or early neonatal deaths and controls were
      live births and neonates who were discharged alive from the hospital and did not
      die before the age of 7 days. The study period was from 1st January up to 30th
      February 2015. Epi-Info version 7.0 and SPSS Version 21 were used for data entry
      and analysis. Descriptive statistics, frequencies, proportions and diagrams were
      used to check the distribution of outcome variable and describe the study
      population. Logistic regression model was used to identify the important factors
      that are associated with perinatal mortality. RESULTS: A total of 1113(376 cases
      and 737 controls) maternal charts were reviewed. The mean age of the mothers for
      cases and controls were 26.47 +/- 4.87 and 26.95 +/- 4.68 respectively. Five
      hundred ninety seven (53.6%) mothers delivered for the first time. Factors that
      are significantly associated with increased risk of perinatal mortality were
      birth interval less than 2 years, preterm delivery, anemia, congenital anomaly,
      previous history of early neonatal death and low birth weight. Use of partograph
      was also associated with decreased risk of perinatal mortality. CONCLUSION: From
      factors that are associated with perinatal mortality, some of them can be
      prevented with early investigation of pregnant mothers on their antenatal care
      follow. Appropriate labor follow-up and monitoring with regular use of
      partograph, immediate newborn care and interventions to delay birth interval also
      minimize perinatal mortality.

PMID- 28747162
TI  - Advanced abdominal pregnancy, with live fetus and severe preeclampsia, case
      report.
AB  - BACKGROUND: Abdominal pregnancy may account for up to 1.4% of all ectopic
      pregnancies. The incidence of abdominal pregnancy differs in various literatures
      and ranges between 1:10,000 pregnancies to 1:30, 000 pregnancies. The clinical
      symptoms of an uncomplicated abdominal pregnancy are unspecific. There are
      reports of maternal and fetal survival from advanced abdominal pregnancies. CASE
      PRESENTATION: Our case was a 26 years old gravida 4, para 3 (2 alive, one early
      neonatal death) woman. She presented to Felegehiwot Referal Hospital with a
      principal complaint of vomiting, epigastric pain, headache, and blurring of
      vision. Emergency cesarean delivery was decided with the impression of bicornuate
      uterus with intrauterine pregnancy, intrauterine growth restriction and sever
      preeclampsia.it was found to be advanced abdominal pregnancy. Placenta was
      removed and pack was used to control bleeding. Both the mother and neonate were
      discharged in a good condition. CONCLUSION: Abdominal pregnancy with live fetus
      is an extremely rare condition and requires a high index of suspicion.
      Endometrial cavity may not be required for development of severe preeclampsia and
      packing is effective in controlling bleeding in selected cases.

PMID- 28747164
TI  - Use of cervicovaginal PAMG-1 protein as a predictor of delivery within seven days
      in pregnancies at risk of premature birth.
AB  - BACKGROUND: To investigate the utility of vaginal placental alpha microglobulin-1
      (PAMG-1) protein as a predictor of preterm delivery within 7 days in pregnancies
      at risk of premature birth. METHODS: This prospective study was performed in
      women at risk of premature birth. The levels of vaginal PAMG-1 and foetal
      fibronectin (fFN) and the transvaginal cervical length measurement (CLM) were
      investigated and compared. RESULTS: Seventy-two pregnant women were included in
      this study. The sensitivities of PAMG-1, fFN and CLM were 73.3, 73.6%, and 52.9%,
      respectively, while the specificities of PAMG-1, fFN and CLM were 92.9%, 94.3%,
      and 90.9%, respectively. The positive predictive values of PAMG-1, fFN and CLM
      were 73.3%, 82.3%, and 64.2%, respectively, and the negative predictive values of
      PAMG-1, fFN and CLM were 92.9%, 90.9%, and 86.2%, respectively. CONCLUSION: The
      diagnostic accuracy of PAMG-1 is similar to that of fFN in terms of preterm
      labour detection within 7 days.

PMID- 28747163
TI  - Incident HIV during pregnancy and early postpartum period: a population-based
      cohort study in a rural area in KwaZulu-Natal, South Africa.
AB  - BACKGROUND: The evidence on the effect of pregnancy on acquiring HIV is
      conflicting, with studies reporting both higher and lower HIV acquisition risk
      during pregnancy when prolonged antiretroviral therapy was accessible. The aim of
      this study was to assess the pregnancy effect on HIV acquisition where
      antiretroviral therapy was widely available in a high HIV prevalence setting.
      METHODS: This is a retrospective cohort study nested within a population-based
      surveillance to determine HIV incidence in HIV-uninfected women from 15 to 49
      years from 2010 through 2015 in rural KwaZulu-Natal. HIV incidence per 100 person
      years according to pregnancy status (not pregnant, pregnant, to eight weeks
      postpartum) were measured in 5260 HIV-uninfected women. Hazard ratios (HR) were
      estimated by Cox proportional hazards regression with pregnancy included as a
      time varying variable. RESULTS: Overall, pregnancy HIV incidence was 4.5 per 100
      person-years (95% CI 3.4-5.8), higher than non-pregnancy (4.0; 95% CI 3.7-4.3)
      and postpartum incidences (4.2 per 100 person-years; 95% CI 2.3-7.6). However,
      adjusting for age, and demographic factors, pregnant women had a lower risk of
      acquiring HIV (HR 0.4; 95% CI 0.2-0.9, P = 0.032) than non-pregnant women; there
      were no differences between postpartum and non-pregnant women (HR 1.2; 95% CI 0.4
      3.2; P = 0.744). In models adjusting for the interaction of age and gravidity,
      pregnant women under 25 years with two or more pregnancies had a 2.3 times
      greater risk of acquiring HIV than their older counterparts (95% CI 1.3-4.3; P =
      0.008). CONCLUSIONS: Pregnancy had a protective effect on HIV acquisition.
      Elevated HIV incidence in younger women appeared to be driven by those with
      higher gravidity. The sexual and biological factors in younger women should be
      explored further in order to design appropriate HIV prevention interventions.

PMID- 28747165
TI  - Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor
      biology in prostate cancer.
AB  - BACKGROUND: Animal model experiments have suggested a role of the DNA repair
      protein ERCC1 (Excision Repair Cross-Complementation Group 1) in prostate cancer
      progression. METHODS: To better understand the impact of ERCC1 protein expression
      in human prostate cancer, a preexisting tissue microarray (TMA) containing more
      than 12,000 prostate cancer specimens was analyzed by immunohistochemistry and
      data were compared with tumor phenotype, PSA recurrence and several of the most
      common genomic alterations (TMPRSS2:ERG fusions: deletions of PTEN, 6q, 5q, 3p).
      RESULTS: ERCC1 staining was seen in 64.7% of 10,436 interpretable tissues and was
      considered weak in 37.1%, moderate in 22.6% and strong in 5% of tumors. High
      level ERCC1 staining was linked to advanced pT stage, high Gleason grade,
      positive lymph nodes, high pre-operative serum PSA, and positive surgical margin
      status (p < 0.0001 each). High ERCC1 expression was strongly associated with an
      elevated risk of PSA recurrence (p < 0.0001). This was independent of established
      prognostic features. A subgroup analysis of cancers defined by comparable
      quantitative Gleason grades revealed that the prognostic impact was mostly driven
      by low-grade tumors with a Gleason 3 + 3 or 3 + 4 (Gleason 4: <=5%). High ERCC1
      expression was strongly associated with the presence of genomic alterations and
      expression levels increased with the number of deletions present in the tumor.
      These latter data suggest a functional relationship of ERCC1 expression with
      genomic instability. CONCLUSION: The results of our study demonstrate that
      expression of ERCC1 - a potential surrogate for genomic instability - is an
      independent prognostic marker in prostate cancer with particular importance in
      low-grade tumors.

PMID- 28747166
TI  - Cascade Fumarate Hydratase mutation screening allows early detection of kidney
      tumour: a case report.
AB  - BACKGROUND: Fumarate hydratase (FH) deficiency is a rare autosomal recessive
      disorder which results in a major defect in cellular metabolism. It presents in
      infancy with progressive encephalopathy, hypotonia, seizures and failure to
      thrive and is often fatal in childhood. It is caused by mutations in the FH gene
      (1q42.1) that result in deficiency of the citric acid cycle enzyme fumarate
      hydratase, resulting in accumulation of fumaric acid. Heterozygous germline
      mutations in the FH gene predispose to an aggressive autosomal dominant inherited
      early-onset kidney cancer syndrome: hereditary leiomyomatosis and renal cell
      cancer (HLRCC). CASE PRESENTATION: Cascade FH mutation screening enabled the
      early diagnosis of a renal tumour in an asymptomatic parent of a child with
      fumarate hydratase deficiency, resulting in timely and possibly life-saving
      treatment. CONCLUSION: While the theoretical risk of kidney cancer in parents of
      children with recessive fumarate hydratase deficiency is well recognized, to our
      knowledge this is the first report of a kidney tumour being detected in a parent
      by screening performed for this indication. This underscores the importance of
      offering lifelong kidney surveillance to such parents and other heterozygous
      relatives of children born with fumarate hydratase deficiency.

PMID- 28747167
TI  - Combined interventions to reduce HIV incidence in KwaZulu-Natal: a modelling
      study.
AB  - BACKGROUND: Combined prevention interventions, including early antiretroviral
      therapy initiation, may substantially reduce HIV incidence in hyperendemic
      settings. Our aim was to assess the potential short-term impact of combined
      interventions on HIV spreading in the adult population of Mbongolwane and Eshowe
      (KwaZulu-Natal, South Africa) using sex- and age-specific scenarios, and age
      targeted interventions. METHODS: A mathematical model was used with data on
      adults (15-59 years) from the Mbongolwane and Eshowe HIV Impact in Population
      Survey to compare the effects of various interventions on the HIV incidence rate.
      These interventions included increase in antiretroviral therapy (ART) coverage
      with extended eligibility criteria, increase in voluntary medical male
      circumcision (VMMC), and implementation of pre-exposure prophylaxis (PrEP) among
      women. RESULTS: With no additional interventions to the ones in place at the time
      of the survey (ART at CD4 < 350 and VMMC), incidence will decrease by 24%
      compared to the baseline rate. The implementation of "ART at CD4<500" or "ART for
      all" would reduce further the incidence rate by additional 8% and 15%
      respectively by 4 years and 20% and 34% by 10 years. Impacts would be higher with
      age-targeted scenarios than without. CONCLUSIONS: In Mbongolwane and Eshowe,
      implementation of the new South African guidelines, recommending ART initiation
      regardless of CD4 count, would accelerate incidence reduction. In this setting,
      combining these guidelines, VMMC, and PrEP among young women could be an
      effective strategy in reducing the incidence to low levels.

PMID- 28747168
TI  - The biobank for the molecular classification of kidney disease: research
      translation and precision medicine in nephrology.
AB  - BACKGROUND: Advances in technology and the ability to interrogate disease
      pathogenesis using systems biology approaches are exploding. As exemplified by
      the substantial progress in the personalized diagnosis and treatment of cancer,
      the application of systems biology to enable precision medicine in other
      disciplines such as Nephrology is well underway. Infrastructure that permits the
      integration of clinical data, patient biospecimens and advanced technologies is
      required for institutions to contribute to, and benefit from research in
      molecular disease classification and to devise specific and patient-oriented
      treatments. METHODS AND RESULTS: We describe the establishment of the Biobank for
      the Molecular Classification of Kidney Disease (BMCKD) at the University of
      Calgary, Alberta, Canada. The BMCKD consists of a fully equipped wet laboratory,
      an information technology infrastructure, and a formal operational, ethical and
      legal framework for banking human biospecimens and storing clinical data. The
      BMCKD first consolidated a large retrospective cohort of kidney biopsy specimens
      to create a population-based renal pathology database and tissue inventory of
      glomerular and other kidney diseases. The BMCKD will continue to prospectively
      bank all kidney biopsies performed in Southern Alberta. The BMCKD is equipped to
      perform molecular, clinical and epidemiologic studies in renal pathology. The
      BMCKD also developed formal biobanking procedures for human specimens such as
      blood, urine and nucleic acids collected for basic and clinical research studies
      or for advanced diagnostic technologies in clinical care. The BMCKD is guided by
      standard operating procedures, an ethics framework and legal agreements with
      stakeholders that include researchers, data custodians and patients. The design
      and structure of the BMCKD permits its inclusion in a wide variety of research
      and clinical activities. CONCLUSION: The BMCKD is a core multidisciplinary
      facility that will bridge basic and clinical research and integrate precision
      medicine into renal pathology and nephrology.

PMID- 28747169
TI  - Optimising decision making on illness absenteeism due to fever and common
      infections within childcare centres: development of a multicomponent intervention
      and study protocol of a cluster randomised controlled trial.
AB  - BACKGROUND: Evidence has shown that children 0-4 year-old attending childcare are
      prone to acquire infections compared to children cared for at home, with fever
      being the most common symptom. Illness absenteeism due to fever and common
      infections is substantial and mostly driven by unrealistic concerns and negative
      attitude towards fever of both childcare staff and parents, resulting in illness
      absenteeism from childcare, work absenteeism among parents and healthcare service
      use. The objective of this study is to optimise decision making among childcare
      staff on illness absenteeism due to fever and common infections in childcare.
      Underlying determinants of behavioural change were targeted by means of a
      multicomponent intervention. METHODS: A multicomponent intervention was developed
      to improve decision making, using the stepwise approach of Intervention Mapping,
      and in close collaboration with stakeholders and experts. The intervention
      consisted of 1) a two-hour educational session on fever among childcare staff; 2)
      an online video for childcare staff and parents emphasising key information of
      the educational session; 3) a decision tool for childcare staff and parents in
      the format of a traffic light system to estimate the severity of illness and
      corresponding advices for childcare staff and parents; 4) an information booklet
      regarding childhood fever, common infections, and self-management strategies for
      childcare staff and parents. The multicomponent intervention will be evaluated in
      a cluster randomised trial with a 12-week follow-up period and absenteeism due to
      illness (defined as the percentage of childcare days absent due to illness on the
      total of childcare days during a 12-week period) as primary outcome measure.
      Secondary outcome measures are: incidence rate and duration of illness episodes,
      knowledge, attitude, self-efficacy, and risk perception on fever and common
      infections of childcare staff and parents, healthcare service use in general and
      paracetamol use, and work absenteeism of parents. DISCUSSION: This study aims to
      develop a multicomponent intervention and to evaluate to what extent illness
      absenteeism due to fever and common infections can be affected by implementing a
      multicomponent intervention addressing decision making and underlying
      determinants among childcare staff and parents of children attending daycare.
      TRIAL REGISTRATION: NTR6402 (registered on 21-apr-2017).

PMID- 28747170
TI  - Spatial prediction and validation of zoonotic hazard through micro-habitat
      properties: where does Puumala hantavirus hole - up?
AB  - BACKGROUND: To predict the risk of infectious diseases originating in wildlife,
      it is important to identify habitats that allow the co-occurrence of pathogens
      and their hosts. Puumala hantavirus (PUUV) is a directly-transmitted RNA virus
      that causes hemorrhagic fever in humans, and is carried and transmitted by the
      bank vole (Myodes glareolus). In northern Sweden, bank voles undergo 3-4 year
      population cycles, during which their spatial distribution varies greatly.
      METHODS: We used boosted regression trees; a technique inspired by machine
      learning, on a 10 - year time-series (fall 2003-2013) to develop a spatial
      predictive model assessing seasonal PUUV hazard using micro-habitat variables in
      a landscape heavily modified by forestry. We validated the models in an
      independent study area approx. 200 km away by predicting seasonal presence of
      infected bank voles in a five-year-period (2007-2010 and 2015). RESULTS: The
      distribution of PUUV-infected voles varied seasonally and inter-annually. In
      spring, micro-habitat variables related to cover and food availability in forests
      predicted both bank vole and infected bank vole presence. In fall, the presence
      of PUUV-infected voles was generally restricted to spruce forests where cover was
      abundant, despite the broad landscape distribution of bank voles in general. We
      hypothesize that the discrepancy in distribution between infected and uninfected
      hosts in fall, was related to higher survival of PUUV and/or PUUV-infected voles
      in the environment, especially where cover is plentiful. CONCLUSIONS: Moist and
      mesic old spruce forests, with abundant cover such as large holes and bilberry
      shrubs, also providing food, were most likely to harbor infected bank voles. The
      models developed using long-term and spatially extensive data can be extrapolated
      to other areas in northern Fennoscandia. To predict the hazard of directly
      transmitted zoonoses in areas with unknown risk status, models based on micro
      habitat variables and developed through machine learning techniques in well
      studied systems, could be used.

PMID- 28747171
TI  - Incorporation of causative quantitative trait nucleotides in single-step GBLUP.
AB  - BACKGROUND: Much effort is put into identifying causative quantitative trait
      nucleotides (QTN) in animal breeding, empowered by the availability of dense
      single nucleotide polymorphism (SNP) information. Genomic selection using
      traditional SNP information is easily implemented for any number of genotyped
      individuals using single-step genomic best linear unbiased predictor (ssGBLUP)
      with the algorithm for proven and young (APY). Our aim was to investigate whether
      ssGBLUP is useful for genomic prediction when some or all QTN are known. METHODS:
      Simulations included 180,000 animals across 11 generations. Phenotypes were
      available for all animals in generations 6 to 10. Genotypes for 60,000 SNPs
      across 10 chromosomes were available for 29,000 individuals. The genetic variance
      was fully accounted for by 100 or 1000 biallelic QTN. Raw genomic relationship
      matrices (GRM) were computed from (a) unweighted SNPs, (b) unweighted SNPs and
      causative QTN, (c) SNPs and causative QTN weighted with results obtained with
      genome-wide association studies, (d) unweighted SNPs and causative QTN with
      simulated weights, (e) only unweighted causative QTN, (f-h) as in (b-d) but using
      only the top 10% causative QTN, and (i) using only causative QTN with simulated
      weight. Predictions were computed by pedigree-based BLUP (PBLUP) and ssGBLUP. Raw
      GRM were blended with 1 or 5% of the numerator relationship matrix, or 1% of the
      identity matrix. Inverses of GRM were obtained directly or with APY. RESULTS:
      Accuracy of breeding values for 5000 genotyped animals in the last generation
      with PBLUP was 0.32, and for ssGBLUP it increased to 0.49 with an unweighted GRM,
      0.53 after adding unweighted QTN, 0.63 when QTN weights were estimated, and 0.89
      when QTN weights were based on true effects known from the simulation. When the
      GRM was constructed from causative QTN only, accuracy was 0.95 and 0.99 with
      blending at 5 and 1%, respectively. Accuracies simulating 1000 QTN were generally
      lower, with a similar trend. Accuracies using the APY inverse were equal or
      higher than those with a regular inverse. CONCLUSIONS: Single-step GBLUP can
      account for causative QTN via a weighted GRM. Accuracy gains are maximum when
      variances of causative QTN are known and blending is at 1%.

PMID- 28747172
TI  - Characteristics of the specific humoral response in patients with advanced solid
      tumors after active immunotherapy with a VEGF vaccine, at different antigen doses
      and using two distinct adjuvants.
AB  - BACKGROUND: CIGB-247, a VSSP-adjuvanted VEGF-based vaccine, was evaluated in a
      phase I clinical trial in patients with advanced solid tumors (CENTAURO).
      Vaccination with the maximum dose of antigen showed an excellent safety profile,
      exhibited the highest immunogenicity and was the only one showing a reduction on
      platelet VEGF bioavailability. However, this antigen dose level did not achieve a
      complete seroconversion rate in vaccinated patients. These clinical results led
      us to the question whether a "reserve" of untapped immune response potential
      against VEGF could exist in cancer patients. To address this matter, CENTAURO-2
      clinical trial was conducted where antigen and VSSP dose scale up were studied,
      and also incorporated the exploration of aluminum phosphate as adjuvant. These
      changes were made with the aim to increase immune response against VEGF. RESULTS:
      The present study reports the characterization of the humoral response elicited
      by CIGB-247 from the combining of different antigen doses and adjuvants. Cancer
      patients were immunologically monitored for approximately 1 year. Vaccination
      with different CIGB-247 formulations exhibited a very positive safety profile.
      Cancer patients developed IgM, IgG or IgA antibodies specific to VEGF. Elicited
      polyclonal antibodies had the ability to block the interaction between VEGF and
      its receptors, VEGFR1 and VEGFR2. The highest humoral response was detected in
      patients immunized with 800 MUg of antigen + 200 MUg of VSSP. Off-protocol long
      term vaccination did not produce negative changes in humoral response.
      CONCLUSIONS: Vaccination with a human VEGF variant molecule as antigen in
      combination with VSSP or aluminum phosphate is immunogenic. The results of this
      study could contribute to the investigation of this vaccine therapy in an
      adequately powered efficacy trial. TRIAL REGISTRATION: Trial registration number:
      RPCEC00000155. Cuban Public Clinical Trial Registry. Date of registration: June
      06, 2013. Available from: http://registroclinico.sld.cu/ .

PMID- 28747173
TI  - Uptake of external cephalic version for term breech presentation: an Australian
      population study, 2002-2012.
AB  - BACKGROUND: The safety, efficacy, and cost-effectiveness of external cephalic
      version (ECV) for term breech presentation has been demonstrated. Clinical
      guidelines recommend ECV for all eligible women, but the uptake of this procedure
      in the Australian healthcare setting is unknown. This study aimed to describe ECV
      uptake in New South Wales, the most populous state of Australia, during 2002 to
      2012. METHODS: Data from routine hospital and birth records were used to identify
      ECVs conducted at >=36 weeks' gestation. Women with ECV were compared to women
      who were potentially eligible for but did not have ECV. Eligibility for ECV was
      based on clinical guidelines. For those with ECV, birth outcomes following
      successful and unsuccessful procedures were examined. RESULTS: In N = 32,321
      singleton breech pregnancies, 10.5% had ECV, 22.3% were ineligible, and 67.2%
      were potentially eligible but did not undergo ECV. Compared to women who were
      eligible but who did not attempt ECV, those who had ECV were more likely to be
      older, multiparous, overseas-born, public patients at delivery, and to deliver in
      tertiary hospitals in urban areas (p < 0.01). Fewer women who underwent ECV
      smoked during pregnancy, fewer were morbidly obese, and fewer had a hypertensive
      disorder of pregnancy, compared to those who were eligible. Caesarean section
      occurred in 25.9% of successful compared to 95.6% of unsuccessful ECVs. Infant
      outcomes did not differ by ECV success. CONCLUSIONS: The majority of women with a
      breech presentation did not receive ECV. It is unclear whether this is
      attributable to issues with service provision or low acceptability among women.
      Policies to improve access to and information about ECV appear necessary to
      improve uptake among women with term breech presentation. Improved data
      collection around the diagnosis of breech presentation, ECV attempts, and
      outcomes may help to identify specific barriers to ECV uptake.

PMID- 28747174
TI  - Knowledge and perceptions about Zika virus in a Middle East country.
AB  - BACKGROUND: Zika virus, an emerging serious infectious disease, is a threat to
      persons living or travelling to regions where it is currently endemic, and also
      to contacts of infected individuals. The aim of this study was to assess
      knowledge about this new public health threat to persons residing in a Middle
      Eastern country. METHODS: We conducted a survey at several international
      universities in Qatar to assess knowledge and awareness about this disease. An
      adapted version of the survey was also conducted using online channels from
      Qatar. RESULTS: The median age of the 446 participants, was 25 years, 280 (63%)
      were females, and 32% were from Gulf Cooperation Council (GCC) or other Middle
      East countries. Based upon their knowledge about availability of a vaccine, role
      of mosquitoes and other modes of transmission, and disease complications, we
      classified respondent's knowledge as "poor" (66%), "basic" (27%) or "broad" (7%).
      Forty-five (16%) persons with poor knowledge considered themselves to be well
      informed. CONCLUSIONS: This report from a sample of persons associated with
      Middle East educational complex, reveals inadequate knowledge about Zika virus, a
      serious emerging infectious disease. Although few cases have been reported from
      the region, future cases are possible, since this area is a transit hub
      connecting currently infected regions to North America, Europe and Asia. As a
      preventive measure, an educational program about Zika virus would be valuable,
      especially for individuals or family members travelling to afflicted regions.

PMID- 28747175
TI  - CD133+ cells are associated with ADIPOCYTOKINES and endothelial dysfunction in
      hemodialysis patients.
AB  - BACKGROUND: Hemodialysis (HD) patients have increased risk of cardiovascular
      disease (CVD). Impaired stem cell health and adipocytokine metabolism may play
      important roles in the complex pathophysiological mechanisms of CVD in this
      patient population. We aimed to investigate the relationships between CD133+ cell
      counts, adipocytokines and parameters of endothelial dysfunction and
      atherosclerosis in HD patients. METHODS: In 58 chronic HD patients
      (male/female:28/30, mean age:58 +/- 14 years), serum levels of interleukin-6 (IL
      6), tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin and resistin
      were measured by ELISA. Left ventricular mass index (LVMI), carotid intima-media
      thickness (CIMT), flow-mediated dilatation (FMD) of the brachial artery were
      measured. CD133+ cells were counted by flow cytometry (BD FACSCalibur-BD
      Bioscience,CA). RESULTS: CD133+ cell counts were inversely associated with FMD (r
      = -0.39, p = 0.007) and positively correlated with serum resistin (r = 0.45, p <
      0.001) and serum TNF-alpha (r = 0.31, p = 0.02). Serum leptin levels were higher
      in high CD133 group compared to low CD133 group [32.37(12.74-72.29) vs 15.50(5.38
      37.12)ng/mL, p = 0.03]. Serum leptin levels were correlated with TNF-alpha(r =
      0.35, p = 0.009). Serum adiponectin levels were negatively correlated with serum
      leptin (r = -0.28, p = 0.03). Serum resistin levels were associated with TNF
      alpha (r = 0.54, p < 0.001) and leptin (r = 0.29, p = 0.03). Serum IL-6 levels
      were significantly associated with LVMI (r = 0.31, p = 0.03). Serum IL-6 levels
      were significantly higher in patients with carotid plaque compared to patients
      without plaque [12.75(9.91-28.68) vs 8.27(5.97-14.04) pg/mL, p = 0.02]. In
      multiple linear regression analysis to determine the factors predicting LogFMD;
      dialysis vintage, LVMI and LogCD133+ cell counts were included as independent
      variables(R = 0.57, adjusted R-square = 0.27, p = 0.001). CD133+ cell count and
      LVMI were found to significantly predict FMD (p = 0.03 and p = 0.04
      respectively). CONCLUSION: CD133+ cells were associated with inflammation and
      endothelial dysfunction in HD patients. Serum leptin, resistin and TNF-alpha
      levels were positively related to CD133+ cell count. Impaired regulation of
      undifferentiated stem cells and adipocytokines might contribute to endothelial
      dysfunction in HD patients.

PMID- 28747176
TI  - Comparative RNA-seq based transcriptome profiling of waterlogging response in
      cucumber hypocotyls reveals novel insights into the de novo adventitious root
      primordia initiation.
AB  - BACKGROUND: Waterlogging is a serious abiotic stress to plant growth because it
      results in the decline in the supplement of oxygen to submerged tissues. Although
      cucumber (Cucumis sativus L.) is sensitive to waterlogging, its ability to
      generate adventitious roots (ARs) facilitates gas diffusion and increases plant
      survival when the oxygen concentration is decreased. To gain a better
      understanding of the molecular mechanisms that enable de novo AR primordia
      emergence upon waterlogging, the RNA sequencing-based transcriptomic responses of
      two contrasting cucumber genotypes, Zaoer-N (waterlogging tolerant) and Pepino
      (waterlogging sensitive), which differed in their abilities to form AR were
      compared. RESULTS: More than 27,000 transcripts were detected in cucumber
      hypocotyls, from which 1494 and 1766 genes in 'Zaoer-N' and 'Pepino',
      respectively, were differentially expressed 2 days after waterlogging. The
      significant positive correlation between RNA sequencing data and a qPCR analysis
      indicated that the identified genes were credible. A comparative analysis
      revealed that genes functioning in carbohydrate mobilization, nitrate
      assimilation, hormone production and signaling pathways, transcription factors
      and cell division might contribute to the waterlogging-triggered AR primordia
      initiation. Ethylene was determined to be an important plant hormone responsible
      for the cucumber ARs initiation. Additionally, genes encoding cytochrome P450,
      ankyrin repeat-containing proteins and sulfite oxidases were determined as
      important in waterlogging acclimation. CONCLUSION: This research broadens our
      understanding of the mechanism underlying waterlogging-triggered ARs emergence,
      and provides valuable information for the breeding of cucumber with enhanced
      waterlogging tolerance.

PMID- 28747177
TI  - Acute coronary syndrome and acute kidney injury: role of inflammation in
      worsening renal function.
AB  - BACKGROUND: Acute Kidney Injury (AKI), a common complication of acute coronary
      syndromes (ACS), is associated with higher mortality and longer hospital stays.
      The role of cytokines and other mediators is unknown in AKI induced by an ACS
      (ACS-AKI), leading to several unanswered questions. The worsening of renal
      function is usually seen as a dichotomous phenomenon instead of a dynamic change,
      so evaluating changes of the renal function in time may provide valuable
      information in the ACS-AKI setting. The aim of this study was to explore
      inflammatory factors associated to de novo kidney injury induced by de novo
      cardiac injury secondary to ACS. METHODS: One hundred four consecutive patients
      with ACS were initially included on the time of admission to the Coronary Unit of
      the Instituto Nacional de Cardiologia in Mexico City, from February to May 2016,
      before any invasive procedure, imaging study, diuretic or anti-platelet therapy.
      White blood count, hemoglobin, NT-ProBNP, troponin I, C-reactive protein,
      albumin, glucose, Na+, K+, blood urea nitrogen (BUN), total cholesterol, HDL,
      LDL, triglycerides, creatinine (Cr), endothelin-1 (ET-1), leukotriene-B4, matrix
      metalloproteinase-2 and -9, tissue inhibitor of metalloproteinases-1, resolvin-D1
      (RvD1), lipoxin-A4 (LXA4), interleukin-1beta, -6, -8, and -10 were measured. We
      finally enrolled 78 patients, and subsequently we identified 15 patients with ACS
      AKI. Correlations were obtained by a Spearman rank test. Low-rank regression,
      splines regressions, and also protein-protein/chemical interactions and pathways
      analyses networks were performed. RESULTS: Positive correlations of DeltaCr were
      found with BUN, admission Cr, GRACE score, IL-1beta, IL-6, NT-ProBNP and age, and
      negative correlations with systolic blood pressure, mean-BP, diastolic-BP and
      LxA4. In the regression analyses IL-10 and RvD1 had positive non-linear
      associations with DeltaCr. ET-1 had also a positive association. Significant non
      linear associations were seen with NT-proBNP, admission Cr, BUN, Na+, K+, WBC,
      age, body mass index, GRACE, SBP, mean-BP and Hb. CONCLUSION: Inflammation and
      its components play an important role in the worsening of renal function in ACS.
      IL-10, ET-1, IL-1beta, TnI, RvD1 and LxA4 represent mediators that might be
      associated with ACS-AKI. IL-6, ET-1, NT-ProBNP might represent crossroads for
      several physiopathological pathways involved in "de novo cardiac injury leading
      to de novo kidney injury".

PMID- 28747178
TI  - Anaerobic bacteria growth in the presence of cathelicidin LL-37 and selected
      ceragenins delivered as magnetic nanoparticles cargo.
AB  - BACKGROUND: Cationic antibacterial peptides (CAPs) and synthetic molecules
      mimicking the amphiphilic structure of CAPs, such as ceragenins, are promising
      compounds for the development of new antimicrobials. RESULTS: We tested the in
      vitro activity of ceragenins CSA-13 and CSA-131 against several anaerobic
      bacteria including Bacteroides spp. and Clostridium difficile. We compared
      results to the activity of cathelicidin LL-37, metronidazole and nanosystems
      developed by attachment of CSA-13 and CSA-131 to magnetic nanoparticles (MNPs).
      The antibacterial effect was tested using killing assay and modified CLSI broth
      microdilution assay. Ceragenins CSA-13 and CSA-131 displayed stronger
      bactericidal activity than LL-37 or metronidazole against all of the tested
      bacterial strains. Additionally CSA-131 revealed an enhanced ability to prevent
      the formation of Bacteroides fragilis and Propionibacterium acnes biofilms.
      CONCLUSIONS: These data confirmed that ceragenins display antimicrobial activity
      against a broad range of microorganisms including anaerobic bacteria and deserve
      further investigations as compounds serving to develop new treatment against
      anaerobic and mixed infections.

PMID- 28747179
TI  - New insights into the roles of cucumber TIR1 homologs and miR393 in regulating
      fruit/seed set development and leaf morphogenesis.
AB  - BACKGROUND: TIR1-like proteins act as auxin receptors and play essential roles in
      auxin-mediated plant development processes. The number of auxin receptor family
      members varies among species. While the functions of auxin receptor genes have
      been widely studied in Arabidopsis, the distinct functions of cucumber (Cucumis
      sativus L.) auxin receptors remains poorly understood. To further our
      understanding of their potential role in cucumber development, two TIR1-like
      genes were identified and designated CsTIR1 and CsAFB2. In the present study,
      tomato (Sonanum lycopersicum) was used as a model to investigate the phenotypic
      and molecular changes associated with the overexpression of CsTIR1 and CsAFB2.
      RESULTS: Differences in the subcellular localizations of CsTIR1 and CsAFB2 were
      identified and both genes were actively expressed in leaf, female flower and
      young fruit tissues of cucumber. Moreover, CsTIR1- and CsAFB2-overexpressing
      lines exhibited pleotropic phenotypes ranging from leaf abnormalities to seed
      germination and parthenocarpic fruit compared with the wild-type plants. To
      further elucidate the regulation of CsTIR1 and CsAFB2, the role of the
      miR393/TIR1 module in regulating cucumber fruit set were investigated. Activation
      of miR393-mediated mRNA cleavage of CsTIR1 and CsAFB2 was revealed by qPCR and
      semi-qPCR, which highlighted the critical role of the miR393/TIR1 module in
      mediating fruit set development in cucumber. CONCLUSION: Our results provide new
      insights into the involvement of CsTIR1 and CsAFB2 in regulating various
      phenotype alterations, and suggest that post-transcriptional regulation of CsTIR1
      and CsAFB2 mediated by miR393 is essential for cucumber fruit set initiation.
      Collectively, these results further clarify the roles of cucumber TIR1 homologs
      and miR393 in regulating fruit/seed set development and leaf morphogenesis.

PMID- 28747180
TI  - Self-reported oral and general health in relation to socioeconomic position.
AB  - BACKGROUND: During the past two decades, several scientific publications from
      different countries have shown how oral health in the population varies with
      social determinants. The aim of the present study was to explore the relationship
      between self-reported oral and general health in relation to different measures
      of socioeconomic position. METHODS: Data were collected from a randomly selected
      sample of the adult population in Sweden (n = 3500, mean age 53.4 years, 53.1%
      women). The response rate was 49.7%. Subjects were interviewed by telephone,
      using a questionnaire including items on self-reported oral and general health,
      socioeconomic position and lifestyle. RESULTS: A significant gradient was found
      for both oral and general health: the lower the socioeconomic position, the
      poorer the health. Socioeconomic position and, above all, economic measures were
      strongly associated with general health (OR 3.95) and with oral health (OR 1.76)
      if having an income below SEK 200,000 per year. Similar results were found in
      multivariate analyses controlling for age, gender and lifestyle variables.
      CONCLUSIONS: For adults, there are clear socioeconomic gradients in self-reported
      oral and general health, irrespective of different socioeconomic measures. Action
      is needed to ensure greater equity of oral and general health.

PMID- 28747181
TI  - Advancing the evidence to improve the nutrition of populations: a refreshed
      vision and scope for Nutrition Journal.

PMID- 28747182
TI  - Recurrent primary mediastinal giant cell tumor of soft tissue with radiological
      findings: a rare case report and literature review.
AB  - BACKGROUND: Giant cell tumor of soft tissue (GCT-ST), which histologically
      resembles GCT of bone, is a rare tumor. Usually, it is located in the lower
      extremities and trunk. GCT-ST, occurring in mediastinum, is extremely rare. CASE
      PRESENTATION: We encountered an 18-year-old Chinese woman who had mild dull pain
      on the left side of back. The following chest computed tomography (CT) showed a
      heterogeneous mass deeply situated in the posterior mediastinum with compression
      of the lung and invasion of the adjacent rib. On magnetic resonance imaging
      (MRI), the tumor exhibited predominantly slight hyperintensity on T2-weighted
      images and intensely heterogeneous enhancement on contrast-enhanced T1-weighted
      images. The whole body bone scan showed a mildly increased radiotracer uptake in
      the proximal portion of the left fifth rib, suggestive of local infiltration by
      the tumor. Surgical resection of the tumor was performed; subsequently, the tumor
      was histopathologically proved as GCT-ST. Three months after the operation, the
      patient developed a local recurrence. A brief discussion about the radiological
      findings, histopathological features, clinical behavior, and a detailed review of
      the relevant literature are presented. CONCLUSIONS: To the best of our knowledge,
      this is the first case about recurrent primary mediastinal GCT-ST, moreover, this
      is the first report to introduce the MRI findings of primary mediastinal GCT-ST.
      The present case highlights the ubiquitous distribution of soft tissue giant cell
      tumor and the importance of considering this tumor in the differential diagnosis
      of posterior mediastinal neoplasms. Also, a long-term follow-up is required to
      properly assess the malignant potential of this tumor.

PMID- 28747183
TI  - Harm reduction in name, but not substance: a comparative analysis of current
      Canadian provincial and territorial policy frameworks.
AB  - BACKGROUND: In Canada, funding, administration, and delivery of health services
      including those targeting people who use drugs-are primarily the responsibility
      of the provinces and territories. Access to harm reduction services varies across
      jurisdictions, possibly reflecting differences in provincial and territorial
      policy commitments. We examined the quality of current provincial and territorial
      harm reduction policies in Canada, relative to how well official documents
      reflect internationally recognized principles and attributes of a harm reduction
      approach. METHODS: We employed an iterative search and screening process to
      generate a corpus of 54 provincial and territorial harm reduction policy
      documents that were current to the end of 2015. Documents were content-analyzed
      using a deductive coding framework comprised of 17 indicators that assessed the
      quality of policies relative to how well they described key population and
      program aspects of a harm reduction approach. RESULTS: Only two jurisdictions had
      current provincial-level, stand-alone harm reduction policies; all other
      documents were focused on either substance use, addiction and/or mental health,
      or sexually transmitted and/or blood-borne infections. Policies rarely named
      specific harm reduction interventions and more frequently referred to generic
      harm reduction programs or services. Only one document met all 17 indicators.
      Very few documents acknowledged that stigma and discrimination are issues faced
      by people who use drugs, that not all substance use is problematic, or that
      people who use drugs are legitimate participants in policymaking. A minority of
      documents recognized that abstaining from substance use is not required to
      receive services. Just over a quarter addressed the risk of drug overdose, and
      even fewer acknowledged the need to apply harm reduction approaches to an array
      of drugs and modes of use. CONCLUSIONS: Current provincial and territorial
      policies offer few robust characterizations of harm reduction or go beyond
      rhetorical or generic support for the approach. By endorsing harm reduction in
      name, but not in substance, provincial and territorial policies may communicate
      to diverse stakeholders a general lack of support for key aspects of the
      approach, potentially challenging efforts to expand harm reduction services.

PMID- 28747184
TI  - MEG2 is regulated by miR-181a-5p and functions as a tumour suppressor gene to
      suppress the proliferation and migration of gastric cancer cells.
AB  - BACKGROUND: Protein-tyrosine phosphatase MEG2 (MEG2) is a classic tyrosine
      specific protein tyrosine phosphatase (PTP). It has been reported that MEG2
      participates in the carcinogenesis of the breast and liver. However, functions of
      MEG2 in gastric cancer remain poorly understood. METHODS: We examined the
      expression of MEG2 protein by western blotting and that of miR-181a-5p by qRT
      PCR. We used bioinformatic analyses to search for miRNAs that potentially target
      MEG2. We performed a luciferase reporter assay to investigate the interaction
      between miR-181a-5p and MEG2. In addition, we assessed the effects of MEG2 and
      miR-181a-5p on gastric cancer cells in vitro and in vivo. RESULTS: We found that
      MEG2 is downregulated in human gastric cancer and that miR-181a-5p is predicted
      to be a potential regulator of MEG2. We also observed that expression of MEG2 is
      reversely correlated with that of miR-181a-5p in gastric cancer. Moreover, we
      observed that MEG2 regulation by miR-181a-5p significantly suppresses the
      proliferation and migration of gastric cancer cells in vitro and decelerates
      tumour growth in vivo. CONCLUSIONS: Our results revealed that MEG2 is a tumour
      suppressor gene and negatively regulated by miR-181a-5p in gastric cancer.

PMID- 28747185
TI  - Efficient organisation of intensive care units with a focus on quality: the non
      physician provider.

PMID- 28747187
TI  - General practitioners' views and preferences about quality improvement feedback
      in preventive care: a cross-sectional study in Switzerland and France.
AB  - BACKGROUND: Feedback is widely used as a strategy to improve the quality of care
      in primary care settings. As part of a study conducted to explore the quality of
      preventive care, we investigated general practitioners' (GPs) views on the
      usefulness of feedback and their preferences regarding how feedback is provided.
      METHODS: This cross-sectional study was conducted in 2015 among randomly selected
      community-based GPs in two regions of Switzerland and France. GPs were asked to
      complete an anonymous questionnaire about how often they provided 12 measures of
      preventive care: blood pressure, weight and height measurements, screening for
      dyslipidemia, at-risk drinking (and advice to reduce for at-risk drinkers),
      smoking (and advice to stop for smokers), colon and prostate cancer, and
      influenza immunization for patients >65 years and at-risk patients. They were
      also asked to estimate the usefulness of a feedback regarding their preventive
      care practice, reason(s) for which a feedback could be useful, and finally, to
      state which type of feedback they would like to receive. Chi-square tests were
      used to compare frequencies. Multivariate logistic regression was used to
      identify factors associated with GPs considering feedback as useful. RESULTS:
      Five hundred eighteen of 1100 GPs (47.1%) returned the questionnaire. They were
      predominantly men (62.5%) and most (40.1%) were aged between 55 and 64 years old.
      Overall, 44.3% stated that a feedback would be useful. Younger GPs and those
      carrying out more measures of preventive care were more likely to consider
      feedback useful. The two main reasons for being interested in feedback were to
      receive knowledge about the study results and to modify or improve practice. The
      two preferred feedback interventions were a brief report and a report with
      specific information regarding prevention best practice, whereas less than 1%
      would like to discuss the results face-to-face with the study investigators.
      CONCLUSIONS: These findings suggest that GPs have preferences regarding the types
      of feedback they would like to receive. Because the implementation of guidelines
      is highly related to the acceptance of feedback, we strongly encourage decision
      makers to take GPs' preferences into account when developing strategies to
      implement guidelines, in order to improve the quality of primary care.

PMID- 28747186
TI  - Understanding differences between summer vs. school obesogenic behaviors of
      children: the structured days hypothesis.
AB  - BACKGROUND: Although the scientific community has acknowledged modest
      improvements can be made to weight status and obesogenic behaviors (i.e.,
      physical activity, sedentary/screen time, diet, and sleep) during the school
      year, studies suggests improvements are erased as elementary-age children are
      released to summer vacation. Emerging evidence shows children return to school
      after summer vacation displaying accelerated weight gain compared to the weight
      gained occurring during the school year. Understanding how summer days differ
      from when children are in school is, therefore, essential. DISCUSSION: There is
      limited evidence on the etiology of accelerated weight gain during summer, with
      few studies comparing obesogenic behaviors on the same children during school and
      summer. For many children, summer days may be analogous to weekend days
      throughout the school year. Weekend days are often limited in consistent and
      formal structure, and thus differ from school days where segmented, pre-planned,
      restrictive, and compulsory components exist that shape obesogenic behaviors. The
      authors hypothesize that obesogenic behaviors are beneficially regulated when
      children are exposed to a structured day (i.e., school weekday) compared to what
      commonly occurs during summer. This is referred to as the 'Structured Days
      Hypothesis' (SDH). To illustrate how the SDH operates, this study examines
      empirical data that compares weekend day (less-structured) versus weekday
      (structured) obesogenic behaviors in U.S. elementary school-aged children. From
      190 studies, 155 (~80%) demonstrate elementary-aged children's obesogenic
      behaviors are more unfavorable during weekend days compared to weekdays.
      CONCLUSION: In light of the SDH, consistent evidence demonstrates the structured
      environment of weekdays may help to protect children by regulating obesogenic
      behaviors, most likely through compulsory physical activity opportunities,
      restricting caloric intake, reducing screen time occasions, and regulating sleep
      schedules. Summer is emerging as the critical period where childhood obesity
      prevention efforts need to be focused. The SDH can help researchers understand
      the drivers of obesogenic behaviors during summer and lead to innovative
      intervention development.

PMID- 28747188
TI  - Transmission dynamics of cholera in Yemen, 2017: a real time forecasting.
AB  - BACKGROUND: A large epidemic of cholera, caused by Vibrio cholerae, serotype
      Ogawa, has been ongoing in Yemen, 2017. To improve the situation awareness, the
      present study aimed to forecast the cholera epidemic, explicitly addressing the
      reporting delay and ascertainment bias. METHODS: Using weekly incidence of
      suspected cases, updated as a revised epidemic curve every week, the reporting
      delay was explicitly incorporated into the estimation model. Using the weekly
      case fatality risk as calculated by the World Health Organization, ascertainment
      bias was adjusted, enabling us to parameterize the family of logistic curves
      (i.e., logistic and generalized logistic models) for describing the unbiased
      incidence in 2017. RESULTS: The cumulative incidence at the end of the epidemic,
      was estimated at 790,778 (95% CI: 700,495, 914,442) cases and 767,029 (95% CI:
      690,877, 871,671) cases, respectively, by using logistic and generalized logistic
      models. It was also estimated that we have just passed through the epidemic peak
      by week 26, 2017. From week 27 onwards, the weekly incidence was predicted to
      decrease. CONCLUSIONS: Cholera epidemic in Yemen, 2017 was predicted to soon
      start to decrease. If the weekly incidence is reported in the up-to-the-minute
      manner and updated in later weeks, not a single data point but the entire
      epidemic curve must be precisely updated.

PMID- 28747189
TI  - Harm reduction in the USA: the research perspective and an archive to David
      Purchase.
AB  - The history of harm reduction in the USA has led to the development of some of
      the most important methods for treating persons for drug use disorders, such as
      methadone and buprenorphine for opiate use disorder. However, there has been
      fierce political resistance to implementation and scale-up of harm reduction in
      the USA. This resistance is rooted in historical demonization of particular
      psychoactive drugs that were associated with stigmatized racial/ethnic
      groups.With the discovery of acquired immunodeficiency syndrome (AIDS) in 1981,
      harm reduction became important not only for treating substance use disorders,
      but for reducing transmission of blood-borne infection. However, within the
      context of the crack cocaine epidemic in the 1980s, it was very difficult to
      implement any programs that appeared to "condone" drug use.It was not until the
      late 1980s that syringe exchange programs began at the state and local level in
      the USA. With funding primarily from state and local governments and the support
      of the North American Syringe Exchange Network (NASEN), there are now
      approximately 200 programs for syringe exchange in the USA. Research has shown
      that these programs have been extremely effective in reducing human
      immunodeficiency virus (HIV) transmission among persons who inject drugs (PWID).
      The programs in the USA also offer many additional services for drug users,
      including condom distribution, referrals to substance abuse treatment, HIV,
      hepatitis C virus (HCV), hepatitis B virus (HBV) counseling and testing, overdose
      education and naloxone distribution to reverse for overdose.Currently, the USA is
      experiencing an opioid/heroin epidemic, with significant increases in overdose
      deaths among drug users. Much of this epidemic is occurring in suburban and rural
      of the country without harm reduction services. The current challenges for harm
      reduction and harm reduction research involve expansion of services to suburban
      and rural areas and implementation science on how to effectively and efficiently
      address HCV transmission and overdose. Most importantly, continued research
      efforts are needed to reduce the stigma of psychoactive drug use. While political
      opposition continues, harm reduction activists and researchers have developed a
      highly effective partnership based on a common core values.

PMID- 28747190
TI  - Bone mineral density in people living with HIV: a narrative review of the
      literature.
AB  - Bone health status is largely absent in South Africa, the main reasons being the
      absence and cost-effectiveness of specific screening equipment for assessing bone
      mineral density (BMD). Various risk factors seem to play a role, some of which
      can be modified to change bone health status. Urbanisation is also a public
      health concern. Changing nutritional, as well as social behaviour, play integral
      roles in the prevalence and incidence of decreased BMD. Furthermore, human
      immunodeficiency virus (HIV) specifically, has a negative impact on BMD and
      although highly active antiretroviral therapy increases the prognosis for HIV
      infected individuals, BMD still seem to decrease further. Dual energy X-ray
      absorptiometry is considered the gold standard for BMD assessment; however,
      recent developments have provided more cost-effective screening methods, among
      which heel quantitative ultrasound appears to be the most widely used in resource
      limited countries such as South Africa.

PMID- 28747191
TI  - Implementation findings from a hybrid III implementation-effectiveness trial of
      the Diabetes Prevention Program (DPP) in the Veterans Health Administration
      (VHA).
AB  - BACKGROUND: The Diabetes Prevention Program (DPP) is an effective lifestyle
      intervention to reduce incidence of type 2 diabetes. However, there are gaps in
      knowledge about how to implement DPP. The aim of this study was to evaluate
      implementation of DPP via assessment of a clinical demonstration in the Veterans
      Health Administration (VHA). METHODS: A 12-month pragmatic clinical trial
      compared weight outcomes between the Veterans Affairs Diabetes Prevention Program
      (VA-DPP) and the usual care MOVE!(r) weight management program (MOVE!). Eligible
      participants had a body mass index (BMI) >=30 kg/m2 (or BMI >= 25 kg/m2 with one
      obesity-related condition), prediabetes (glycosylated hemoglobin (HbA1c) 5.7-6.5%
      or fasting plasma glucose (FPG) 100-125 mg/dL), lived within 60 min of their VA
      site, and had not participated in a weight management program within the last
      year. Established evaluation and implementation frameworks were used to guide the
      implementation evaluation. Implementation barriers and facilitators, delivery
      fidelity, participant satisfaction, and implementation costs were assessed. Using
      micro-costing methods, costs for assessment of eligibility and scheduling and
      maintaining adherence per participant, as well as cost of delivery per session,
      were also assessed. RESULTS: Several barriers and facilitators to Reach,
      Adoption, Implementation, Effectiveness and Maintenance were identified; barriers
      related to Reach were the largest challenge encountered by site teams. Fidelity
      was higher for VA-DPP delivery compared to MOVE! for five of seven domains
      assessed. Participant satisfaction was high in both programs, but higher in VA
      DPP for most items. Based on micro-costing methods, cost of assessment for
      eligibility was $68/individual assessed, cost of scheduling and maintaining
      adherence was $328/participant, and cost of delivery was $101/session.
      CONCLUSIONS: Multi-faceted strategies are needed to reach targeted participants
      and successfully implement DPP. Costs for assessing patients for eligibility need
      to be carefully considered while still maximizing reach to the targeted
      population.

PMID- 28747192
TI  - The European ME/CFS Biomarker Landscape project: an initiative of the European
      network EUROMENE.
AB  - Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a common and
      severe disease with a considerable social and economic impact. So far, the
      etiology is not known, and neither a diagnostic marker nor licensed treatments
      are available yet. The EUROMENE network of European researchers and clinicians
      aims to promote cooperation and advance research on ME/CFS. To improve diagnosis
      and facilitate the analysis of clinical trials surrogate markers are urgently
      needed. As a first step for developing such biomarkers for clinical use a
      database of active biomarker research in Europe was established called the ME/CFS
      EUROMENE Biomarker Landscape project and the results are presented in this
      review. Further we suggest strategies to improve biomarker development and
      encourage researchers to take these into consideration for designing and
      reporting biomarker studies.

PMID- 28747193
TI  - Impact of improved recording of work-relatedness in primary care visits at
      occupational health services on sickness absences: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Employment protects and fosters health. Occupational health services,
      particularly in Finland, have a central role in protecting employee health and
      preventing work ability problems. However, primary care within occupational
      health services is currently underused in informing preventive activities. This
      study was designed to assess whether the recording of work ability problems and
      improvement of follow-up of work-related primary care visits can reduce sickness
      absences and work disability pensions after 1 year. METHODS/DESIGN: A pragmatic
      trial will be conducted using patient electronic registers and registers of the
      central pensions agency in Finland. Twenty-two occupational health centres will
      be randomised to intervention and control groups. Intervention units will receive
      training to improve recording of work ability illnesses in the primary care
      setting and improved follow-up procedures. The intervention impact will be
      assessed through examining rates of sickness absence across intervention and
      control clinics as well as before and after the intervention. DISCUSSION: The
      trial will develop knowledge of the intervention potential of primary care for
      preventing work disability pensions and sickness absence. The use of routine
      patient registers and pensions registers to assess the outcomes of a randomised
      controlled trial will bring forward trial methodology, particularly when using
      register-based data. If successful, the intervention will improve the quality of
      occupational health care primary care and contribute to reducing work disability.
      TRIAL REGISTRATION: ISRCTN Registry reference number ISRCTN45728263 . Registered
      on 18 April 2016.

PMID- 28747194
TI  - Obesity in Scotland: a persistent inequality.
AB  - BACKGROUND: Obesity is a health problem in its own right and a risk factor for
      other conditions such as cardiovascular disease. The prevalence of overweight and
      obesity increased in Scotland between 1995 and 2008 with socio-economic
      inequalities persisting in adults over time and increasing in children. This
      paper explores changes in the underlying distribution of body mass index (BMI)
      which is less well understood. METHODS: Using data from the Scottish Health
      Survey (SHeS) between 1995 and 2014 for adults aged 18-64 years, we calculated
      population distributions for BMI for the population overall, and for age, sex and
      deprivation strata. We used SHeS data for children aged 2-15 years between 1998
      and 2014, in addition to data from the Child Health Systems Programme (CHSP)
      collected from primary one (P1) children in participating local authorities, to
      describe the overall trends and to compare trends in inequalities by deprivation
      strata. RESULTS: Amongst adults, the BMI distribution shifted upwards, with a
      large proportion of the population gaining a small amount of weight between 1995
      and 2008 before subsequently stabilising across the distribution. In men the
      prevalence of obesity showed a linear deprivation gradient in 1995 but over time
      obesity declined in the least deprived quintile while the remaining four
      quintiles converged (and stabilised). In contrast, a persistent and generally
      linear gradient is evident among women for most of the 1995-2014 period. For
      those aged 2-15 years, obesity increased between 1998 and 2014 for the most
      deprived 40% of children contrasted with stable trends for the least deprived.
      The surveillance data for P1 children in Scotland showed a persistent inequality
      between 2005/06 and 2014/15 though it was less clear if this is widening.
      CONCLUSIONS: The BMI distribution for adults increased between 1995 and 2008 with
      a large proportion of the population gaining a small amount of weight before
      stabilising across the distribution. Inequalities in obesity persist for adults
      (with different underlying patterns evident for men and women), and may be
      widening for children. Actions to reduce the obesogenic environment, including
      structural changes not dependent on individual agency, are urgently needed if the
      long-term health, social and inequality consequences of obesity are to be
      reduced.

PMID- 28747195
TI  - Oleic acid induces down-regulation of the granulosa cell identity marker FOXL2,
      and up-regulation of the Sertoli cell marker SOX9 in bovine granulosa cells.
AB  - During negative energy balance, the concentration of different fatty acids,
      especially of oleic acid (OA) increases in the follicular fluid of cattle.
      Previously, we showed that OA induced morphological, physiological and molecular
      changes in cultured bovine granulosa cells. In our present study we analyzed
      effects of OA on the expression of markers for granulosa and Sertoli cell
      identity, FOXL2 and SOX9, respectively, in addition to effects on the FOXL2
      regulated genes ESR2, FST, PTGS2 and PPARG. The results showed that OA down
      regulated FOXL2, ESR2, FST and PPARG but up-regulated PTGS2 and SOX9. From these
      data we conclude that OA can compromise granulosa cell functionality and may
      initiate trans-differentiation processes in bovine granulosa cells. This novel
      mechanism may be causally involved in postpartum fertility problems of lactating
      dairy cows.

PMID- 28747196
TI  - "If donors woke up tomorrow and said we can't fund you, what would we do?" A
      health system dynamics analysis of implementation of PMTCT option B+ in Uganda.
AB  - BACKGROUND: In October 2012 Uganda extended its prevention of mother to child HIV
      transmission (PMTCT) policy to Option B+, providing lifelong antiretroviral
      treatment for HIV positive pregnant and breastfeeding women. The rapid changes
      and adoptions of new PMTCT policies have not been accompanied by health systems
      research to explore health system preparedness to implement such programmes. The
      implementation of Option B+ provides many lessons which can inform the shift to
      'Universal Test and Treat', a policy which many sub-Saharan African countries are
      preparing to adopt, despite fragile health systems. METHODS: This qualitative
      study of PMTCT Option B+ implementation in Uganda three years following the
      policy adoption, uses the health system dynamics framework to explore the impacts
      of this programme on ten elements of the health system. Qualitative data were
      gathered through rapid appraisal during in-country field work. Key informant
      interviews and focus group discussions (FGDs) were undertaken with the Ministry
      of Health, implementing partners, multilateral agencies, district management
      teams, facility-based health workers and community cadres. A total of 82
      individual interviews and 16 focus group discussions were completed. We conducted
      a simple manifest analysis, using the ten elements of a health system for
      grouping data into categories and themes. RESULTS: Of the ten elements in the
      health system dynamics framework, context and resources (finances, infrastructure
      & supplies, and human resources) were the most influential in the implementation
      of Option B+ in Uganda. Support from international actors and implementing
      partners attempted to strengthen resources at district level, but had unintended
      consequences of creating dependence and uncertainty regarding sustainability.
      CONCLUSIONS: The health system dynamics framework offers a novel approach to
      analysis of the effects of implementation of a new policy on critical elements of
      the health system. Its emphasis on relationships between system elements,
      population and context is helpful in unpacking impacts of and reactions to
      pressures on the system, which adds value beyond some previous frameworks.

PMID- 28747197
TI  - Prenatal and postnatal bisphenol A exposure and social impairment in 4-year-old
      children.
AB  - BACKGROUND: Prenatal and postnatal exposure to bisphenol A (BPA) may affect early
      brain development. Rodent studies suggest that prenatal and postnatal
      neurodevelopmental toxicity from BPA exposure may manifest as social deficits in
      offspring. We investigated the association between prenatal and postnatal
      exposure to BPA and social impairments in a sample of 4-year-old children.
      METHODS: We recruited second-trimester pregnant women between 2008 and 2011, and
      measured their creatinine-adjusted prenatal urine BPA levels. In 2014-2015, a
      subset of 4-year-old children born to these women underwent neurobehavioral
      assessment and physical examination. We collected urine and blood from the
      children and assessed social impairments, including deficits in social
      interaction, social communication, and other behavior patterns using the Korean
      version of the Social Communication Questionnaire (K-SCQ) (n = 304). We examined
      social impairments associated with prenatal exposure at mid-term pregnancy and
      postnatal exposure to BPA at 4 years of age, using linear and piecewise linear
      regression models. RESULTS: The relationship between prenatal BPA exposure and
      social communication was non-linear and statistically significant at or above the
      flexion point for BPA levels of 3.0 MUg/g creatinine in girls (58.4%, 95%
      confidence interval [CI], 6.5% to 135.8%). Each 2-fold increase in postnatal BPA
      exposure was significantly associated with an 11.8% (95% CI, 0.6% to 24.3%)
      increase in impairment in social communication in 4-year old girls, as indicated
      by the linear regression model. CONCLUSION: Prenatal and postnatal BPA exposure
      is associated with social impairment at 4 years of age, particularly in girls.

PMID- 28747198
TI  - Population-based prevalence survey of follicular trachoma and trachomatous
      trichiasis in the Casamance region of Senegal.
AB  - BACKGROUND: Trachoma, caused by ocular infection with Chlamydia trachomatis, is
      the leading infectious cause of blindness worldwide. We conducted the first
      population-based trachoma prevalence survey in the Casamance region of Senegal to
      enable the Senegalese National Eye Care Programme (NECP) to plan its trachoma
      control activities. The World Health Organization (WHO) guidelines state that any
      individual with trachomatous trichiasis (TT) should be offered surgery, but that
      surgery should be prioritised where the prevalence is >0.1%, and that districts
      and communities with a trachomatous inflammation, follicular (TF) prevalence of
      >=10% in 1-9 year-olds should receive mass antibiotic treatment annually for a
      minimum of three years, along with hygiene promotion and environmental
      improvement, before re-assessing the prevalence to determine whether treatment
      can be discontinued (when TF prevalence in 1-9 year-olds falls <5%). METHODS:
      Local healthcare workers conducted a population-based household survey in four
      districts of the Bignona Department of Casamance region to estimate the
      prevalence of TF in 1-9 year-olds, and TT in >=15 year-olds. Children's facial
      cleanliness (ocular and/or nasal discharge, dirt on the face, flies on the face)
      was measured at time of examination. Risk factor questionnaires were completed at
      the household level. RESULTS: Sixty communities participated with a total
      censused population of 5580 individuals. The cluster-, age- and sex-adjusted
      estimated prevalence of TF in 1-9 year-olds was 2.5% (95% Confidence Interval
      (CI) 1.8-3.6) (38/1425) at the regional level and <5% in all districts, although
      the upper 95%CI exceeded 5% in all but one district. The prevalence of TT in
      those aged >=15 years was estimated to be 1.4% (95%CI 1.0-1.9) (40/2744) at the
      regional level and >1% in all districts. CONCLUSION: With a prevalence <5%, TF
      does not appear to be a significant public health problem in this region.
      However, TF monitoring and surveillance at sub-district level will be required to
      ensure that elimination targets are sustained and that TF does not re-emerge as a
      public health problem. TT surgery remains the priority for trachoma elimination
      efforts in the region, with an estimated 1819 TT surgeries to conduct.

PMID- 28747199
TI  - Malaria epidemiology in low-endemicity areas of the northern coast of Ecuador:
      high prevalence of asymptomatic infections.
AB  - BACKGROUND: The recent scale-up in malaria control measures in Latin America has
      resulted in a significant decrease in the number of reported cases in several
      countries including Ecuador, where it presented a low malaria incidence in recent
      years (558 reported cases in 2015) with occasional outbreaks of both Plasmodium
      falciparum and Plasmodium vivax in the coastal and Amazonian regions. This
      success in malaria control in recent years has led Ecuador to transition its
      malaria policy from control to elimination. RESULTS: This study evaluated the
      general knowledge, attitude and practices (KAP) about malaria, as well as its
      prevalence in four communities of an endemic area in northwest Ecuador. A total
      of 258 interviews to assess KAP in the community indicated that most people in
      the study area have a basic knowledge about the disease but did not use to
      contribute to its control. Six hundred and forty-eight blood samples were
      collected and analysed by thick blood smear and real-time PCR. In addition, the
      distribution of the infections was mapped in the study communities. Although, no
      parasites were found by microscopy, by PCR the total malaria prevalence was 7.5%
      (6.9% P. vivax and 0.6% P. falciparum), much higher than expected and comparable
      to that reported in endemic areas of neighbouring countries with higher malaria
      transmission. Serology using ELISA and immunofluorescence indicated 27%
      respondents for P. vivax and 22% respondents for P. falciparum. CONCLUSIONS:
      Results suggest that despite a great malaria reduction in Ecuador, transition
      from control to elimination would demand further improvement in malaria
      diagnostics, including active case detection to identify and treat parasite
      asymptomatic carriers, as well as community participation in its elimination.

PMID- 28747200
TI  - Rubella, herpes simplex virus type 2 and preeclampsia.
AB  - BACKGROUND: Preeclampsia is a major health problem. Although, the pathophysiology
      of preeclampsia is not fully understood, there are recent studies on association
      between infections and preeclampsia. OBJECTIVE: The aim of the present study was
      to investigate the association between maternal seropositivity of rubella, Herpes
      simplex virus type 2 (HSV-2) and preeclampsia. METHOD: A case -controls study (90
      women in each arm) was conducted at Saad Abualila Maternity Hospital, Khartoum,
      Sudan. The cases were women with preeclampsia and the controls were healthy
      pregnant women. Rubella and HSV-2 IgG antibodies were analysed in the maternal
      sera of all of the participants using ELISA. RESULTS: There was no significant
      difference in the age, parity and gestational age between the two groups.
      Maternal serum IgG seropositivity for rubella (92.2% vs. 34.4%, P < 0.001) and
      HSV-2 (87.8% vs. 57.8%, P < 0.001) were significantly higher in preeclampsia than
      in the controls. There was no significant difference in the maternal serum IgM
      seropositivity for rubella (3.3% vs. 2.2%, P = 0.650) and HSV-2 (2.2% vs. 1.1%, P
      = 0.560). All the IgM seropositive cases were IgG seropositive too. In binary
      logistic regression women with rubella (OR = 4.93; 95% CI = 2.082-11.692, P <
      0.001) and HSV-2 (OR = 5.54; 95% CI = 2.48-12.38, P < 0.001) IgG seropositivity
      were at higher risk for preeclampsia. CONCLUSION: In the current study rubella
      and HSV-2 IgG seropositivity is associated with preeclampsia. Preventive measure
      should be implemented.

PMID- 28747201
TI  - Intravenous superoxide dismutase as a protective agent to prevent impairment of
      lung function induced by high tidal volume ventilation.
AB  - BACKGROUND: Positive-pressure mechanical ventilation is essential in assisting
      patients with respiratory failure in the intensive care unit and facilitating
      oxygenation in the operating room. However, it was also recognized as a primary
      factor leading to hospital-acquired pulmonary dysfunction, in which pulmonary
      oxidative stress and lung inflammation had been known to play important roles.
      Cu/Zn superoxide dismutase (SOD) is an important antioxidant, and possesses anti
      inflammatory capacity. In this study, we aimed to study the efficacy of Cu/Zn
      SOD, administered intravenously during high tidal volume (HTV) ventilation, to
      prevent impairment of lung function. METHODS: Thirty-eight male Sprague-Dawley
      rats were divided into 3 groups: 5 h ventilation with (A) low tidal volume (LTV;
      8 mL/kg; n = 10), (B) high tidal volume (HTV; 18 mL/kg; n = 14), or (C) HTV and
      intravenous treatment of Cu/Zn SOD at a dose of 1000 U/kg/h (HTV + SOD; n = 14).
      Lung function was evaluated both at baseline and after 5-h ventilation. Lung
      injury was assessed by histological examination, lung water and protein contents
      in the bronchoalveolar lavage fluid (BALF). Pulmonary oxidative stress was
      examined by concentrations of methylguanidine (MG) and malondialdehyde (MDA) in
      BALF, and antioxidative activity by protein expression of glutathione peroxidase
      1 (GPx-1) in the lung. Severity of lung inflammation was evaluated by white blood
      cell and differential count in BALF, and protein expression of inducible nitric
      oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis
      factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9), and mRNA expression
      of nuclear factor-kappaB (NF-kappaB) in the lung. We also examined protein
      expression of surfactant protein (SP)-A and D and we measured hourly changes in
      serum nitric oxide (NO) level. RESULTS: Five hours of LTV ventilation did not
      induce a major change in lung function, whereas 5 h of HTV ventilation induced
      apparent combined restrictive and obstructive lung disorder, together with
      increased pulmonary oxidative stress, decreased anti-oxidative activity and
      increased lung inflammation (P < 0.05). HTV ventilation also decreased SP-A and
      SP-D expression and suppressed serum NO level during the time course of
      ventilation. Cu/Zn SOD administered intravenously during HTV ventilation
      effectively reversed associated pulmonary oxidative stress and lung inflammation
      (P < 0.05); moreover, it preserved SP-A and SP-D expressions in the lung and
      increased serum nitric oxide (NO) level, enhancing vascular NO bioavailability.
      CONCLUSIONS: HTV ventilation can induce combined restrictive and obstructive lung
      disorders. Intravenous administration of Cu/Zn SOD during HTV ventilation can
      prevent lung function impairment and lung injury via reducing pulmonary oxidative
      stress and lung inflammation, preserving pulmonary surfactant expression, and
      enhancing vascular NO bioavailability.

PMID- 28747202
TI  - Knowledge of non-communicable diseases and practices related to healthy
      lifestyles among adolescents, in state schools of a selected educational division
      in Sri Lanka.
AB  - BACKGROUND: Behaviors established during the adolescence have life-long
      consequences to the onset of non-communicable diseases (NCDs) in later life.
      Therefore, it is essential to understand adolescents' knowledge and practices
      with the intention of developing preventive programs focusing on this age group.
      The objective of the study was to assess knowledge about selected NCDs, and
      lifestyle choices among school students aged 17-19 years in state schools of the
      Maharagama Educational Division, Sri Lanka. METHODS: A descriptive, cross
      sectional study was conducted among students aged 17-19 years attending state
      schools in Maharagama Education Division. A total of 634 students were selected
      from 9 schools conducting Advance Level classes. Stratified sampling was done
      based on stream of study and the number needed from each stratum was decided
      according to probability proportionate to size which was followed by cluster
      sampling within the strata to select the classes included. Data were collected
      using a self-administered-questionnaire on socio-demographic characteristics and
      economic status; lifestyle-related practices; knowledge on Non-Communicable 
      Diseases. Logistic regression was used to assess the associations. RESULTS:
      Proportion students with good overall knowledge was 43%(n = 272). Forty-three
      percent (n = 275) consumed a healthy diet, and 20%(n = 129) engaged in adequate
      physical activity 3%(n = 18) of students were current smokers and 12%(n = 73)
      current alcohol users 12%(n = 73). Overall "good" knowledge about NCDs was
      associated with being a science stream student(OR = 3.3; 95%CI:2.1-5.2). Healthy
      diet was associated with female sex (OR = 2.1; 95%CI: 1.5-3.0), and adequate
      physical activity with male sex (OR = 2.1; 95% CI:1.4-3.2), non-science-stream
      (OR = 2.1; 95%CI:1.2-3.7) and upper socio economic status (OR = 2.0; 95%CI:1.3
      3.0). Non-smoking was associated with overall good knowledge (OR = 4.1; 95%CI:1.2
      13.7) and female sex (OR = 0;95%CI:1.5-infinity). Abstinence from alcohol was
      associated with being a female (OR = 6.9; 95%CI:3.4-13.9), and with mother and
      fathers' education level of > General-Certificate of Examinations Ordinary Level
      (GCE O/L) (OR = 2.9; 95%CI:1.1-8.4 and OR = 3.5; 95%CI:1.1-11.2 respectively).
      CONCLUSION: Knowledge about NCDs and healthy lifestyle-practices were poor among
      school students aged 17-19 years. Lack of knowledge about healthy and unhealthy
      behaviors highlights the importance of carrying out regular surveillance for NCD
      risk factors, and initiating programs for the prevention of NCDs amongst
      adolescents.

PMID- 28747203
TI  - Migraine and percutaneous patent foramen ovale closure: a systematic review and
      meta-analysis.
AB  - BACKGROUND: The association between patent foramen ovale (PFO) and migraine with
      aura (MA) is well established. However, the benefits of PFO closure are less
      certain in patients with migraine without aura (MwoA). METHODS: We systematically
      searched Pubmed for pertinent clinical studies published from January 2000 to
      July 2015. The primary end-point was the elimination or significant improvement
      of migraine symptoms after PFO closure. RESULTS: Upon screening an initial list
      of 315 publications, we identified eight studies that included 546 patients.
      Overall, our analysis indicated a significant improvement of migraine in 81% of
      MA cases compared to only 63% of MwoA cases. The summary odds ratio was 2.5 (95%
      confidence interval 1.09-5.73), and the benefits of PFO closure were
      significantly greater for patients with MA compared to patients with MwoA (P =
      0.03). CONCLUSIONS: The presence of aura provides a reference standard for the
      clinical selection of patients with migraine for PFO closure intervention.

PMID- 28747204
TI  - Just fun or a prejudice? - physician stereotypes in common jokes and their
      attribution to medical specialties by undergraduate medical students.
AB  - BACKGROUND: Many jokes exist about stereotypical attributes of physicians in
      various specialties, which could lead to prejudices against physicians from a
      specific specialty. It is unknown whether and when medical students are aware of
      stereotypes about different specialties. The goal of this study was to analyze
      the degree of stereotypes that exist about medical specialties amongst
      undergraduate medical students at different stages of their education. METHODS:
      One hundred fifty-two jokes with different content about attributes of physicians
      from different specialties were found by an internet search. In total, 36
      characteristics of the five specialties of anesthesia, general surgery, internal
      medicine, orthopedics, and psychiatry were extracted from the jokes and they
      constituted the basis for the development of an online questionnaire. The
      questionnaire allowed each characteristic to be assigned to one of the five
      specialties and was sent to 999 undergraduate medical students from semester 1,
      7, and 12 at the Medical Faculty of Hamburg University. RESULTS: Three hundred
      eight (30.8%) of the invited students completed the survey. The characteristics
      of general surgeons and psychiatrists were assigned congruently most frequently
      (>50%). For internists and orthopedics, there was a significantly more congruent
      assignment of the characteristics by final year students versus students in their
      first semester. Male students assigned the characteristics of anesthetists and
      internists significantly more congruently than female students. The three
      characteristics "...are a bit slow on the uptake", "...consider income to be
      relatively unimportant", and "...apologize a lot" were not assigned to any of the
      five specialties by more than 50% of the students. CONCLUSIONS: While stereotypes
      about physicians from certain specialties seem to exist commonly, medical
      educators need to be aware that stereotypes about specialties might develop
      during undergraduate medical training. In order to support students in their
      professional identity formation without developing stereotypes, medical educators
      should receive training. Performing a similar study with physicians in
      postgraduate training would shed some light on stereotypes and prejudices that
      might develop at a later stage in medical education.

PMID- 28747205
TI  - Detection of antibiotic resistance is essential for gonorrhoea point-of-care
      testing: a mathematical modelling study.
AB  - BACKGROUND: Antibiotic resistance is threatening to make gonorrhoea untreatable.
      Point-of-care (POC) tests that detect resistance promise individually tailored
      treatment, but might lead to more treatment and higher levels of resistance. We
      investigate the impact of POC tests on antibiotic-resistant gonorrhoea. METHODS:
      We used data about the prevalence and incidence of gonorrhoea in men who have sex
      with men (MSM) and heterosexual men and women (HMW) to calibrate a mathematical
      gonorrhoea transmission model. With this model, we simulated four clinical
      pathways for the diagnosis and treatment of gonorrhoea: POC test with (POC+R) and
      without (POC-R) resistance detection, culture and nucleic acid amplification
      tests (NAATs). We calculated the proportion of resistant infections and cases
      averted after 5 years, and compared how fast resistant infections spread in the
      populations. RESULTS: The proportion of resistant infections after 30 years is
      lowest for POC+R (median MSM: 0.18%, HMW: 0.12%), and increases for culture (MSM:
      1.19%, HMW: 0.13%), NAAT (MSM: 100%, HMW: 99.27%), and POC-R (MSM: 100%, HMW:
      99.73%). Per 100 000 persons, NAAT leads to 36 366 (median MSM) and 1228 (median
      HMW) observed cases after 5 years. Compared with NAAT, POC+R averts more cases
      after 5 years (median MSM: 3353, HMW: 118). POC tests that detect resistance with
      intermediate sensitivity slow down resistance spread more than NAAT. POC tests
      with very high sensitivity for the detection of resistance are needed to slow
      down resistance spread more than by using culture. CONCLUSIONS: POC with high
      sensitivity to detect antibiotic resistance can keep gonorrhoea treatable longer
      than culture or NAAT. POC tests without reliable resistance detection should not
      be introduced because they can accelerate the spread of antibiotic-resistant
      gonorrhoea.

PMID- 28747206
TI  - Laparoscopic sacrocolpopexy versus vaginal sacrospinous fixation for vaginal
      vault prolapse, a randomized controlled trial: SALTO-2 trial, study protocol.
AB  - BACKGROUND: Hysterectomy is one of the most performed surgical procedures during
      lifetime. Almost 10 % of women who have had a hysterectomy because of prolapse
      symptoms, will visit a gynaecologist for a surgical correction of a vaginal vault
      prolapse thereafter. Vaginal vault prolapse can be corrected by many different
      surgical procedures. A Cochrane review comparing abdominal sacrocolpopexy to
      vaginal sacrospinous fixation considered the open abdominal procedure as the
      treatment of first choice for prolapse of the vaginal vault, although operation
      time and hospital stay is longer. Literature also shows that hospital stay and
      blood loss are less after a laparoscopic sacrocolpopexy compared to the abdominal
      technique. To date, it is unclear which of these techniques leads to the best
      operative result and the highest patient satisfaction. Prospective trials
      comparing vaginal sacrospinous fixation and laparoscopic sacrocolpopexy are
      lacking. The aim of this randomized trial is to compare the disease specific
      quality of life of the vaginal sacrospinous fixation and laparoscopic
      sacrocolpopexy as the treatment of vaginal vault prolapse. METHODS: We will
      perform a multicentre prospective randomized controlled trial. Women with a post
      hysterectomy symptomatic, POP-Q stage >=2, vaginal vault prolapse will be
      included. Participants will be randomized to the vaginal sacrospinous fixation
      group or the laparoscopic sacrocolpopexy group. Primary outcome is disease
      specific quality of life at 12 months follow-up. Secondary outcome will be the
      effect of the surgical treatment on prolapse related symptoms, sexual
      functioning, procedure related morbidity, hospital stay, post-operative recovery,
      anatomical results using the POP-Q classification after one and 5 years follow
      up, type and number of re-interventions, costs and cost-effectiveness. Analysis
      will be performed according to the intention to treat principle and not as a per
      protocol analysis. With a power of 90% and a level of 0.05, the calculated sample
      size necessary is 96 patients. Taking into account 10% attrition, a number of 106
      patients (53 in each arm) will be included. DISCUSSION: The SALTO-2 trial is a
      randomized controlled multicentre trial to evaluate whether the laparoscopic
      sacrocolpopexy or vaginal sacrospinous fixation is the first-choice surgical
      treatment in patients with a stage >=2 vault prolapse. TRIAL REGISTRATION:
      Netherlands Trial Register (NTR): NTR3977 ; Registered 28 April 2013.

PMID- 28747207
TI  - Lessons learnt from the MAGNET Malawian-German Hospital Partnership: the German
      perspective on contributions to patient care and capacity development.
AB  - BACKGROUND: Malawi is a low-income country with one of the highest HIV prevalence
      rates worldwide (Kendig et al., Trop Med Health 41:163-170, 2013). The health
      system depends largely on external funding. Official German development aid has
      supported health care in Malawi for many years (German Embassy Lilongwe, The
      German Development Cooperation in Malawi), including placing medical doctors in
      various departments of the Kamuzu Central Hospital (KCH) in Lilongwe. In 2008, a
      hospital partnership called MAGNET (Malawi German Networking for Capacity
      Building in Treatment, Training and Research at KCH) evolved as part of the
      German ESTHER network. The partnership was abruptly terminated in 2015. METHODS:
      We reviewed 35 partnership documents and conducted an online survey of
      partnership stakeholders to retrospectively assess the hospital partnership based
      on the Capacity WORKS model of the German Corporation for International
      Cooperation (GIZ). This model evaluates systems' management and implementation to
      understand and support the functioning of cooperation within societies. Based on
      this model, we considered the five success factors for cooperation management:
      (1) strategy, (2) cooperation, (3) steering, (4) processes, and (5) learning and
      innovation. In an online survey, we used an adapted version of the partnership
      evaluation tool by the Centers for Disease Control and Prevention (CDC). RESULTS:
      From 2008 to 2015, the MAGNET partnership contributed to capacity building and
      improved patient care in the KCH Medical Department through clinical care,
      technical support, teaching and trainings, and operations research based on
      mutually agreed upon objectives. The MAGNET partnership was implemented in three
      phases during which there were changes in leadership in the Medical Department
      and the hospital, contractual policies, funder priorities and the competing
      influences of other actors. Communication and follow up among partners worked
      best during phases when a German doctor was onsite. The partnership was judged as
      a positive driver for change and support within the Medical Department, but
      eventually failed to implement self-sustainable, robust processes within the
      partnership to cope with multiple changes and challenges. CONCLUSION: The MAGNET
      partnership made a considerable contribution to patient care, continuous medical
      education and operations research at KCH, despite its abrupt termination. Changes
      in the institutional infrastructure, donor policy and interpersonal relations
      contributed to the loss of shared expectations and the end of the project.
      Institutional-hospital partnerships, like MAGNET, can make a valuable
      contribution to health care provision and hence a wider health agenda, provided
      there is a flexible, mutually agreed upon strategy, personal commitment,
      continuous communication and robust processes. However, partnership projects
      remain vulnerable to the influences of external actors and structures. Ministries
      of Health and donor agencies should appreciate the particular strength of
      hospital partnerships.

PMID- 28747208
TI  - GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In CLL
      (GALACTIC) trial: study protocol for a phase II/III randomised controlled trial.
AB  - BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common adult
      leukaemia. Achieving minimal residual disease (MRD) negativity in CLL is an
      independent predictor of survival even with a variety of different treatment
      approaches and regardless of the line of therapy. METHODS/DESIGN: GA101
      (obinutuzumab) monocLonal Antibody as Consolidation Therapy In CLL (GALACTIC) is
      a seamless phase II/III, multi-centre, randomised, controlled, open, parallel
      group trial for patients with CLL who have recently responded to chemotherapy.
      Participants will be randomised to receive either obinutuzumab (GA-101)
      consolidation or no treatment (as is standard). The phase II trial will assess
      safety and short-term efficacy in order to advise on continuation to a phase III
      trial. The primary objective for phase III is to assess the effect of
      consolidation therapy on progression-free survival (PFS). One hundred eighty
      eight participants are planned to be recruited from forty research centres in the
      United Kingdom. DISCUSSION: There is evidence that achieving MRD eradication with
      alemtuzumab consolidation is associated with improvements in survival and time to
      progression. This trial will assess whether obinutuzumab is safe in a
      consolidation setting and effective at eradicating MRD and improving PFS. TRIAL
      REGISTRATION: ISRCTN, 64035629 . Registered on 12 January 2015. EudraCT, 2014
      000880-42 . Registered on 12 November 2014.

PMID- 28747209
TI  - Hypoglycemic effects of Acacia nilotica in type II diabetes: a research proposal.
AB  - OBJECTIVE: Diabetes mellitus is a common metabolic disorder throughout the world
      which can negatively affect the function of various body organs. Due to their
      availability and few side effects, herbal medicines have been proposed as
      suitable alternatives in the management of diabetes. Previous studies have
      confirmed the anti diabetic properties of Acacia nilotica. The hypoglycemic
      effects of this plant have been attributed to its role in stimulating the islets
      of Langerhans to produce more insulin. The present paper describes a systematic
      review protocol for the assessment of the hypoglycemic effects of A. nilotica.
      MAIN TEXTS: Randomized and non-randomized placebo-controlled clinical trials,
      performed during 1999-2016 will be included. The outcomes will be measured
      through FBS, GCT, GTT, and OGTT in all of studies and in addition to these tests,
      will be measured 2HPP and HbA1c level in human study. Well-known databases will
      be searched for selected key terms A. nilotica, type II diabetes and
      hypoglycemia. The quality assessment of the selected papers will be evaluated
      based on SYRCLE and Cochrane Risk of Bias Tool. We believe that our findings will
      provide details about difficulties researchers face during the design of
      protocols or implementation of scientific studies. Ultimately, the publication of
      our findings will facilitate the development of effective treatment strategies to
      promote the health of people with type II DM. PROSPERO registration
      CRD42016053141.

PMID- 28747210
TI  - The medical food Souvenaid affects brain phospholipid metabolism in mild
      Alzheimer's disease: results from a randomized controlled trial.
AB  - BACKGROUND: Synaptic dysfunction contributes to cognitive impairment in
      Alzheimer's disease and may be countered by increased intake of nutrients that
      target brain phospholipid metabolism. In this study, we explored whether the
      medical food Souvenaid affects brain phospholipid metabolism in patients with
      Alzheimer's disease. METHODS: Thirty-four drug-naive patients with mild
      Alzheimer's disease (Mini Mental State Examination score >=20) were enrolled in
      this exploratory, double-blind, randomized controlled study. Before and after 4
      week intervention with Souvenaid or an isocaloric control product, phosphorus and
      proton magnetic resonance spectroscopy (MRS) was performed to assess surrogate
      measures of phospholipid synthesis and breakdown (phosphomonoesters [PME] and
      phosphodiesters [PDEs]), neural integrity (N-acetyl aspartate), gliosis (myo
      inositol), and choline metabolism (choline-containing compounds [tCho]). The main
      outcome parameters were PME and PDE signal intensities and the PME/PDE ratio.
      RESULTS: MRS data from 33 patients (60-86 years old; 42% males; Souvenaid arm n =
      16; control arm n = 17) were analyzed. PME/PDE and tCho were higher after 4 weeks
      of Souvenaid compared with control (PME/PDE least squares [LS] mean difference
      [95% CI] 0.18 [0.06-0.30], p = 0.005; tCho LS mean difference [95% CI] 0.01 [0.00
      0.02], p = 0.019). No significant differences were observed in the other MRS
      outcome parameters. CONCLUSIONS: MRS reveals that Souvenaid affects brain
      phospholipid metabolism in mild Alzheimer's disease, in line with findings in
      preclinical studies. TRIAL REGISTRATION: Netherlands Trial Register, NTR3346 .
      Registered on 13 March 2012.

PMID- 28747211
TI  - Fluorodeoxyglucose-positron emission tomography/computed tomography imaging
      features of colloid adenocarcinoma of the lung: a case report.
AB  - BACKGROUND: Colloid adenocarcinoma of the lung is a rare subtype of variants of
      invasive adenocarcinomas. We report the appearance of this unusual entity on 18F
      fluorodeoxyglucose positron emission tomography/computed tomography. CASE
      PRESENTATION: A 60-year-old man of Chinese Han nationality coughed with a little
      white sputum for 1 month. Chest computed tomography showed multiple bilateral
      subpleural nodules and plaques accompanied by air bronchograms, which were most
      concentrated in the lower lobe of his right lung. Positron emission tomography
      indicated increased radioactivity uptake with a maximum standardized uptake value
      of 3.5. Positron emission tomography/computed tomography showed a soft tissue
      density lesion in his left adrenal gland with a maximum standardized uptake value
      of 4.1. The positron emission tomography/computed tomography appearance suggested
      a primary colloid adenocarcinoma in the lower lobe of his right lung accompanied
      by intrapulmonary and left adrenal gland metastases. The diagnostic rate of
      colloid adenocarcinoma can be increased by combining the anatomic and metabolic
      information of lesions. CONCLUSIONS: The advantage of positron emission
      tomography/computed tomography in the diagnosis of colloid adenocarcinoma, as
      with other cancers, is the ability to locate extrapulmonary disease, facilitating
      clinical staging.

PMID- 28747212
TI  - Sublingual misoprostol and hyperpyrexia: case report with temperature curve.
AB  - BACKGROUND: Misoprostol has a wide range of applications in obstetrics and
      gynaecology. It is widely recommended by WHO, FIGO and ACOG for the treatment of
      postpartum haemorrhage due to it safety and cost-effectiveness. However, usage
      might be associated to hyperpyrexia and shivering. CASE PRESENTATION: We present
      a 30 year old Cameroonian female gravida 1 para 1 who had a vaginal delivery at
      40 weeks of gestation complicated by primary postpartum haemorrhage (PPH). PPH
      was managed by sublingual misoprostol that induced shivering and hyperpyrexia
      managed successfully with paracetamol and cooling. CONCLUSIONS: The occurrence of
      fever and shivering should be kept in mind when administering misoprostol for
      PPH.

PMID- 28747213
TI  - Cesarean delivery technique among HIV positive women with sub-optimal antenatal
      care uptake at the Douala General Hospital, Cameroon: case series report.
AB  - BACKGROUND: The human immunodeficiency virus (HIV) pandemic is a serious public
      health problem worldwide, especially in low-income countries of sub-Saharan
      Africa (SSA). The prevention of mother to child transmission of HIV (PMTCT) is a
      major concern to those countries. Cesarean section has been described in the
      literature to be effective in the prevention of mother to child transmission
      (MTCT). CASE SERIES PRESENTATION: We present a series of seven cases of HIV
      positive pregnant women with sub-optimal antenatal care up-take who delivered by
      cesarean section at the Department of Obstetrics and Gynecology of the Douala
      General Hospital. During the cesarean section the fetal head was delivered
      through the uterine incision without rupture of amniotic membranes. The amniotic
      membranes were ruptured after delivery of the fetal head, and then the rest of
      the body was delivered. CONCLUSIONS: Most of the study participants had multiple
      risk factors for preterm labour. When a good cesarean section technique is used
      in women with high viral load and low CD4 counts, risk of MTCT HIV are greatly
      reduced even in low-income countries.

PMID- 28747215
TI  - Sphingolipid metabolism potential in fecal microbiome and bronchiolitis in
      infants: a case-control study.
AB  - OBJECTIVE: Emerging evidence demonstrated that the structure of fecal microbiome
      is associated with the likelihood of bronchiolitis in infants. However, no study
      has examined functional profiles of fecal microbiome in infants with
      bronchiolitis. In this context, we conducted a case-control study. As a part of
      multicenter prospective study, we collected stool samples from 40 infants
      hospitalized with bronchiolitis (cases). We concurrently enrolled 115 age-matched
      healthy controls. RESULTS: First, by applying 16S rRNA gene sequencing to these
      155 fecal samples, we identified the taxonomic profiles of fecal microbiome.
      Next, based on the taxonomy data, we inferred the functional capabilities of
      fecal microbiome and tested for differences in the functional capabilities
      between cases and controls. Overall, the median age was 3 months and 45% were
      female. Among 274 metabolic pathways surveyed, there were significant differences
      between bronchiolitis cases and healthy controls for 37 pathways, including lipid
      metabolic pathways (false discovery rate [FDR] <0.05). Particularly, the fecal
      microbiome of bronchiolitis cases had consistently higher abundances of gene
      function related to the sphingolipid metabolic pathways compared to that of
      controls (FDR <0.05). These pathways were more abundant in infants with
      Bacteroides-dominant microbiome profile compared to the others (FDR <0.001). On
      the basis of the predicted metagenome in this case-control study, we found
      significant differences in the functional potential of fecal microbiome between
      infants with bronchiolitis and healthy controls. Although causal inferences
      remain premature, our data suggest a potential link between the bacteria-derived
      metabolites, modulations of host immune response, and development of
      bronchiolitis.

PMID- 28747214
TI  - Culturing and transcriptome profiling of progenitor-like colonies derived from
      adult mouse pancreas.
AB  - BACKGROUND: Transplantation of insulin-producing cells is considered an important
      diabetes therapy. Many research studies have shown that insulin-producing cells
      can be derived from the in-vitro cultured pancreatic colonies with self-renewal
      ability and multilineage potential. Even though these progenitor-like colonies
      have been prepared from adult pancreas cells, the efficient culture method is
      hardly established and regulation of the colonies is rarely known. We confirmed
      previously that single cells acquired from adult mouse pancreas could form cyst
      like colonies in a 3D semi-solid system containing Matrigel and methylcellulose.
      These colonies could be passaged continuously without losing progenitor-like
      capacity. In the previous culturing system, however, conditioned medium from
      murine embryonic-stem-cell-derived pancreatic-like cells was used. This
      unregulated ingredient may reduce repeatability and affect following study. Thus,
      a new culturing system with certain components needs to be developed. METHODS:
      Single cell suspension was acquired from adult mouse pancreas and cultured in a
      Matrigel-based 3D system with epidermal growth factor, Nicotinamide, B27, and
      Noggin to form ring colonies. Serial-passage assay was performed to evaluate self
      renewal ability. Real-time polymerase chain reaction and immunostaining were used
      to detect the expression of progenitor-related genes. A 2D differentiation method
      was used to testify the multilineage potency of the colonies. High-throughput
      sequencing (HTS) of the colonies was performed to profile the differentially
      expressed genes. RESULTS: We developed a 3D culturing system deprived of
      conditioned medium to propagate those colonies with high proliferative
      efficiency. HTS of the transcriptome of mRNAs, microRNAs (miRNAs) and long
      noncoding RNAs (lncRNAs) showed differentially expressed genes compared to the
      whole pancreas (as control). In mRNAs, several surface marker genes were
      identified in the colonies. Moreover in noncoding RNAs, miR-21a, miR-31 and miR
      155 were upregulated and miR-217, miR-802 and miR-375 were downregulated in
      colonies along with a number of other miRNAs and lncRNAs. CONCLUSIONS: Our
      results offer an efficient culture system for pancreatic progenitor-like colonies
      and HTS of the colonies serves as a target resource for following study of in
      vitro cultured pancreatic progenitors. These findings should also contribute to
      our understanding of the transcriptional regulation of these progenitor-like
      colonies and the mechanisms behind their functions.

PMID- 28747216
TI  - The detection of great crested newts year round via environmental DNA analysis.
AB  - OBJECTIVE: Analysis of environmental DNA (eDNA) is a method that has been used
      for the detection of various species within water bodies. The great crested newt
      (Triturus cristatus) has a short eDNA survey season (mid-April to June). Here we
      investigate whether this season could be extended into other months using the
      current methodology as stipulated by Natural England. RESULTS: Here we present
      data to show that in monthly water samples taken from two ponds (March 2014
      February 2015) we were able to detect great crested newt DNA in all months in at
      least one of the ponds. Similar levels of great crested newt eDNA (i.e. highly
      positive identification) were detected through the months of March-August,
      suggesting it may be possible to extend the current survey window. In order to
      determine how applicable these observations are for ponds throughout the rest of
      the UK, further work in multiple other ponds over multiple seasons is suggested.
      Nevertheless, the current work clearly demonstrates, in two ponds, the efficacy
      and reproducibility of eDNA detection for determining the presence of great
      crested newts.

PMID- 28747217
TI  - Persistence of Candida dubliniensis and lung function in patients with cystic
      fibrosis.
AB  - OBJECTIVES: Candida dubliniensis is an emerging yeast and demonstrated a high
      adherence property to cystic fibrosis respiratory tract. Therefore, it is
      important to determine the persistence of C. dubliniensis and to assess the
      possible relationship to the body mass index (BMI) and forced expiratory volume
      in 1st second (FEV1). RESULTS: Candida isolates were identified by MALDI-TOF MS
      to species level from 40/52 (76.9%) cystic fibrosis patients. C. dubliniensis was
      the most common organism isolated from 50/77 (65%) lower respiratory specimens of
      29 patients. Patients with persistent C. dubliniensis isolates have higher mean
      BMI in comparison to intermittent C. dubliniensis group. However, this difference
      did not reach statistical significance (P = 0.539). In contrast, patients with
      persistent C. dubliniensis isolates have significantly lower FEV1% mean in
      comparison to intermittent C. dubliniensis group particularly at initial two
      visits (P < 0.05); however, at subsequent visit the difference observed was not
      statistically significant (P = 0.456). The persistence of C. dubliniensis is more
      frequent in adults having more advanced disease, co-infections with chronic P.
      aeruginosa, cystic fibrosis related diabetes, long-term nebulized tobramycin and
      oral Zithromax therapy than patients with intermittent C. dubliniensis. Patients
      with persistent C. dubliniensis have lower FEV1 percentage and higher BMI than
      the intermittent C. dubliniensis.

PMID- 28747218
TI  - Risk factors for type 2 diabetes mellitus among out-patients in Ho, the Volta
      regional capital of Ghana: a case-control study.
AB  - BACKGROUND: The prevalence of type 2 diabetes mellitus in developing countries
      like Ghana continues to rise. This study seeks to assess the risk factors of type
      2 diabetes mellitus in a Ghanaian setting. An unmatched case-control study among
      patients receiving care at the out-patient departments of the two major hospitals
      in the Ho Municipality. Patients diagnosed with type 2 diabetes mellitus were
      recruited. Appropriate controls with similar ages who were also patients
      receiving care at the out-patient department of these hospitals were recruited.
      Both cases and controls were administered a questionnaire that comprises of
      standardized and validated tools. These tools include WHO STEPs instrument,
      general practice physical activity questionnaire and rapid eating and activity
      assessment for patients. Additionally, the research participants were made to
      undergo physical examinations for weight, height, waist circumference and
      laboratory testing of fasting venous blood to assess the biochemical factors of
      interest namely fasting blood glucose and fasting lipids. Analysis of data was
      done using STATA version 11. RESULTS: A total of 136 (48 cases and 88 controls)
      participants of which 95 [39 (81.25%) cases and 56 (63.64%) controls] respondents
      underwent laboratory testing for fasting blood glucose and fasting blood lipid
      (total cholesterol, HDL cholesterol and triglycerides). Participants were aged
      between 35 and 62 years. This study reveals a number of risk factors for type 2
      diabetes mellitus. Individuals in the middle socio-economic class have a greater
      risk of developing type 2 diabetes mellitus with an OR of 5.03 (p < 0.003; 95% CI
      1.71-14.74). Eating large quantities/servings of fruits per seating provides
      protection against development of type 2 diabetes mellitus. A low physical
      activity level is a valid determinant of type 2 diabetes mellitus irrespective of
      body mass index, socio-economic level or place of residence. CONCLUSIONS:
      Individuals within the middle socio-economic level, who are physically inactive
      and do not consume large amounts of fruit are at greatest risk of developing type
      2 diabetes mellitus. Living in a rural setting is attendant with high levels of
      physical activity this tends to protect rural residents from type 2 diabetes
      mellitus. Physical activity level confounds the relationship between place of
      residence and development of type 2 diabetes mellitus. Local policies should be
      realigned to attract individual of the middle socio-economic level to live in
      rural areas where they are more likely to be both physically active and consume
      more fruits thus averting the risks of developing T2DM.

PMID- 28747219
TI  - Role of eculizumab in a pediatric refractory gemcitabine-induced thrombotic
      microangiopathy: a case report.
AB  - BACKGROUND: The incidence of gemcitabine-induced hemolytic uremic syndrome has
      already been described in adults. Several approaches have been employed in the
      treatment of gemcitabine-induced hemolytic uremic syndrome with different
      outcomes. One of the most promising agents is eculizumab, which is a monoclonal
      antibody directed against C5 complement protein. CASE PRESENTATION: We reported
      the case of a 3-year-old white boy with medulloblastoma who underwent high-dose
      chemotherapy and craniospinal irradiation. Afterwards he started maintenance
      chemotherapy with gemcitabine and oxaliplatin. After five courses he presented a
      progressive clinical worsening, which resulted in a systemic thrombotic
      microangiopathy. Initially he was treated with rituximab without clinical
      improvement. Therefore he started therapy with repeated cycles of eculizumab.
      After seven infusions he showed a gradual improvement and finally a complete
      remission of gemcitabine-induced hemolytic uremic syndrome. CONCLUSIONS:
      Eculizumab prevents serious complement-mediated vascular damage for chemotherapy
      induced thrombotic microangiopathy in pediatric cases.

PMID- 28747220
TI  - A novel hand-assisted laparoscopic versus conventional laparoscopic right
      hemicolectomy for right colon cancer: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Although conventional laparoscopic and hand-assisted laparoscopic
      surgery for colorectal cancer is widely used today, there remain many technical
      challenges especially for right colon cancer in obese patients. Herein, we
      develop a novel hand-assisted laparoscopic surgery (HALS) with complete mesocolic
      excision (CME), D3 lymphadenectomy, and a total "no-touch" isolation technique
      (HALS-CME) in right hemicolectomy to overcome these issues. According to previous
      clinic practice, this novel procedure is not only feasible and safe but has
      several technical merits. However, the feasibility, short-term minimally invasive
      virtues, long-term oncological superiority, and potential total "no-touch"
      isolation technique benefits of HALS-CME should be confirmed by a prospective
      randomized controlled trial. METHODS/DESIGN: This is a single-center, open-label,
      noninferiority, randomized controlled trial. Eligible participants will be
      randomly assigned to the HALS-CME group or to the laparoscopic surgery with CME,
      D3 lymphadenectomy, and total "no-touch" isolation technique (LAP-CME) group, or
      to conventional laparoscopic surgery with CME and D3 lymphadenectomy (cLAP) group
      at a 1:1:1 ratio using a centralized randomization list. Primary endpoints
      include safety, efficacy, and being oncologically clear, and 3-year disease-free,
      progression-free, and overall survival. Second endpoints include operative
      outcomes (operation time, blood loss, and incision length), pathologic evaluation
      (grading the plane of surgery, length of proximal and distal resection margins,
      distance between the tumor and the central arterial high tie, distance between
      the nearest bowel wall and the same high tie, area of mesentery resected, width
      of the chain of lymph-adipose tissue, length of the central lymph-adipose chain,
      number of harvested lymph nodes), and postoperative outcomes (pain intensity,
      postoperative inflammatory and immune responses, postoperative recovery).
      DISCUSSION: This trial will provide valuable clinical evidence for the
      feasibility, safety, and potential total "no-touch" isolation technique benefits
      of HALS-CME for right hemicolectomy. The hypothesis is that HALS-CME is feasible
      for the radical D3 resection of right colon cancer and offers short-term safety
      and long-term oncological superiority compared with conventional laparoscopic
      surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02625272 . Registered on 8
      December 2015.

PMID- 28747221
TI  - Prevalence of heartworm in dogs and cats of Madrid, Spain.
AB  - BACKGROUND: Dirofilaria immitis causes heartworm disease, a chronic and
      potentially fatal cardiopulmonary disease which mainly affects dogs and cats. It
      is present in most of Spain, due to favourable climatic factors. Madrid, located
      in the centre of the Iberian Peninsula, is the most highly populated city in the
      country. There is a lack of current data on canine heartworm and there are no
      published epidemiological data regarding feline heartworm in this region,
      therefore the aim of this study was to assess the prevalence and current
      distribution of canine and feline dirofilariosis in the province of Madrid.
      METHODS: Serum samples from 1716 dogs and 531 cats, from animals living in the
      metropolitan area of Madrid and adjacent areas, were studied. All the samples,
      either from cats and dogs, were tested for circulating D. immitis antigens using
      a commercial immunochromatographic test kit. Furthermore, to establish the
      seroprevalence of heartworm infection in cats, serological techniques for anti-D.
      immitis and anti-Wolbachia antibody detection were used. RESULTS: Prevalence of
      D. immitis in the canine population of Madrid was 3%, showing an increase in
      comparison to previous data. The presence of heartworm in the city centre could
      be influenced by the presence of Urban Heat Islands, while the positive dogs from
      metropolitan and adjacent areas were mainly located under the influence of
      rivers. Regarding cats, 0.2% were positive to the antigens test and 7.3% were
      seropositive to both anti-D. immitis and Wolbachia surface protein antibodies,
      which demonstrate the presence of feline heartworm in Madrid. Seropositive cats
      were present in the same areas where positive dogs were found. Indoor/outdoor
      cats showed the highest seroprevalence whereas the lowest corresponded to indoor
      cats, demonstrating that prophylactic treatments should be carried out regardless
      of lifestyle. Infection was found in 2.2% of dogs and 6.7% of the cats < 1 year
      old, which indicates that early preventive campaigns in puppies and kittens
      should be implemented. CONCLUSIONS: The results point to the need for adequate
      prophylactic measures through the administration of macrocyclic lactones in
      animals living in Madrid. Veterinarians should be aware of the presence of this
      disease and include heartworm in the differential diagnosis when a pet presents
      with symptoms compatible with D. immitis.

PMID- 28747222
TI  - Prevalence and seasonal transmission of Schistosoma haematobium infection among
      school-aged children in Kaedi town, southern Mauritania.
AB  - BACKGROUND: Mauritania is at the fringe of transmission of human schistosomiasis,
      which mainly occurs in the southern and southeastern parts of the country. This
      study aimed to assess the influence of rainfall seasonality on the prevalence of
      Schistosoma haematobium infection among school-aged children in Kaedi, southern
      Mauritania. METHODS: Cross-sectional surveys (i.e. parasitological, malacological
      and observations on water-related human activities) were carried out in Kaedi
      between September 2014 and May 2015, during both the wet and dry seasons. A total
      of 2162 children aged 5-15 years provided a single urine sample that was
      subjected to S. haematobium diagnosis. Snails were sampled and checked for
      cercarial shedding. Water contact patterns of the local population were recorded
      by direct observation. RESULTS: The prevalence of S. haematobium was 4.0%
      (86/2162, 95% confidence interval (CI): 3.2-4.9%) with a geometric mean egg count
      per 10 ml of urine of 3.7 (95% CI: 2.8-4.3). Being male (adjusted odds ratio
      (aOR) 1.78, 95% CI: 1.13-2.80), being at primary school (aOR 1.73, 95% CI: 1.04
      2.87) and dry season (aOR 0.56, 95% CI: 0.35-0.89) were significantly associated
      with S. haematobium. Among 284 potential intermediate host snail specimens
      collected over the rainy and dry seasons, three species were identified: Bulinus
      senegalensis (n = 13) and B. forskalii (n = 161) in the rainy season, and B.
      truncatus (n = 157) in the wet season. No snail was shedding cercariae. On
      average, seven human water contacts were recorded per hour per observer over a 28
      day observation period. Twelve types of water contact activities were identified
      among which, swimming/bathing was predominant (n = 3788, 36.9%), followed by
      washing clothes (n = 2016, 19.7%) and washing dishes (n = 1322, 12.9%). Females
      (n = 5270, 51.4%) were slightly more in contact with water than males (n = 4983,
      48.6%). The average time spent in the water per person per day was 14.2 min (95%
      CI: 13.8-14.6 min). The frequency and duration of water contact followed a
      seasonal pattern. CONCLUSION: Our findings demonstrate a low prevalence and
      intensity of S. haematobium among school-aged children in Kaedi. Appropriate
      integrated control measures, including health education among at-risk communities
      and snail control may help to interrupt transmission of S. haematobium in Kaedi.

PMID- 28747223
TI  - Return of chloroquine sensitivity to Africa? Surveillance of African Plasmodium
      falciparum chloroquine resistance through malaria imported to China.
AB  - BACKGROUND: Chloroquine (CQ) was the cornerstone of anti-malarial treatment in
      Africa for almost 50 years, but has been widely withdrawn due to the emergence
      and spread of resistance. Recent reports have suggested that CQ-susceptibility
      may return following the cessation of CQ usage. Here, we monitor CQ sensitivity
      and determine the prevalence of genetic polymorphisms in the CQ resistance
      transporter gene (pfcrt) of Plasmodium falciparum isolates recently imported from
      Africa to China. METHODS: Blood samples were collected from falciparum malaria
      patients returning to China from various countries in Africa. Isolates were
      tested for their sensitivity to CQ using the SYBR Green I test ex vivo, and for a
      subset of samples, in vitro following culture adaptation. Mutations at positions
      72-76 and codon 220 of the pfcrt gene were analyzed by sequencing and confirmed
      by PCR-RFLP. Correlations between drug sensitivity and pfcrt polymorphisms were
      investigated. RESULTS: Of 32 culture adapted isolates assayed, 17 (53.1%), 6
      (18.8%) and 9 (28.1%) were classified as sensitive, moderately resistant, and
      highly resistant, respectively. In vitro CQ susceptibility was related to point
      mutations in the pfcrt gene, the results indicating a strong association between
      pfcrt genotype and drug sensitivity. A total of 292 isolates were typed at the
      pfcrt locus, and the prevalence of the wild type (CQ sensitive) haplotype CVMNK
      in isolates from East, South, North, West and Central Africa were 91.4%, 80.0%,
      73.3%, 53.3% and 51.7%, respectively. The only mutant haplotype observed was
      CVIET, and this was almost always linked to an additional mutation at A220S.
      CONCLUSIONS: Our results suggest that a reduction in drug pressure following
      withdrawal of CQ as a first-line drug may lead to a resurgence in CQ sensitive
      parasites. The prevalence of wild-type pfcrt CQ sensitive parasites from East,
      South and North Africa was higher than from the West and Central areas, but this
      varied greatly between countries. Further surveillance is required to assess
      whether the prevalence of CQ resistant parasites will continue to decrease in the
      absence of widespread CQ usage.

PMID- 28747224
TI  - Regions of common inter-individual DNA methylation differences in human
      monocytes: genetic basis and potential function.
AB  - BACKGROUND: There is increasing evidence for inter-individual methylation
      differences at CpG dinucleotides in the human genome, but the regional extent and
      function of these differences have not yet been studied in detail. For
      identifying regions of common methylation differences, we used whole genome
      bisulfite sequencing data of monocytes from five donors and a novel bioinformatic
      strategy. RESULTS: We identified 157 differentially methylated regions (DMRs)
      with four or more CpGs, almost none of which has been described before. The DMRs
      fall into different chromatin states, where methylation is inversely correlated
      with active, but not repressive histone marks. However, methylation is not
      correlated with the expression of associated genes. High-resolution single
      nucleotide polymorphism (SNP) genotyping of the five donors revealed evidence for
      a role of cis-acting genetic variation in establishing methylation patterns. To
      validate this finding in a larger cohort, we performed genome-wide association
      studies (GWAS) using SNP genotypes and 450k array methylation data from blood
      samples of 1128 individuals. Only 30/157 (19%) DMRs include at least one 450k
      CpG, which shows that these arrays miss a large proportion of DNA methylation
      variation. In most cases, the GWAS peak overlapped the CpG position, and these
      regions are enriched for CREB group, NF-1, Sp100 and CTCF binding motifs. In two
      cases, there was tentative evidence for a trans-effect by KRAB zinc finger
      proteins. CONCLUSIONS: Allele-specific DNA methylation occurs in discrete
      chromosomal regions and is driven by genetic variation in cis and trans, but in
      general has little effect on gene expression.

PMID- 28747225
TI  - Epidemiology and outcomes of people with dementia, delirium, and unspecified
      cognitive impairment in the general hospital: prospective cohort study of 10,014
      admissions.
AB  - BACKGROUND: Cognitive impairment of various kinds is common in older people
      admitted to hospital, but previous research has usually focused on single
      conditions in highly-selected groups and has rarely examined associations with
      outcomes. This study examined prevalence and outcomes of cognitive impairment in
      a large unselected cohort of people aged 65+ with an emergency medical admission.
      METHODS: Between January 1, 2012, and June 30, 2013, admissions to a single
      general hospital acute medical unit aged 65+ underwent a structured specialist
      nurse assessment (n = 10,014). We defined 'cognitive spectrum disorder' (CSD) as
      any combination of delirium, known dementia, or Abbreviated Mental Test (AMT)
      score < 8/10. Routine data for length of stay (LOS), mortality, and readmission
      were linked to examine associations with outcomes. RESULTS: A CSD was present in
      38.5% of all patients admitted aged over 65, and in more than half of those aged
      over 85. Overall, 16.7% of older people admitted had delirium alone, 7.9%
      delirium superimposed on known dementia, 9.4% known dementia alone, and 4.5%
      unspecified cognitive impairment (AMT score < 8/10, no delirium, no known
      dementia). Of those with known dementia, 45.8% had delirium superimposed.
      Outcomes were worse in those with CSD compared to those without - LOS 25.0 vs.
      11.8 days, 30-day mortality 13.6% vs. 9.0%, 1-year mortality 40.0% vs. 26.0%, 1
      year death or readmission 62.4% vs. 51.5% (all P < 0.01). There was relatively
      little difference by CSD type, although people with delirium superimposed on
      dementia had the longest LOS, and people with dementia the worst mortality at 1
      year. CONCLUSIONS: CSD is common in older inpatients and associated with
      considerably worse outcomes, with little variation between different types of
      CSD. Healthcare systems should systematically identify and develop care pathways
      for older people with CSD admitted as medical emergencies, and avoid only
      focusing on condition-specific pathways such as those for dementia or delirium
      alone.

PMID- 28747226
TI  - Self-declared stock ownership and association with positive trial outcome in
      randomized controlled trials with binary outcomes published in general medical
      journals: a cross-sectional study.
AB  - BACKGROUND: Describe the prevalence and types of conflicts of interest (COI) in
      published randomized controlled trials (RCTs) in general medical journals with a
      binary primary outcome and assess the association between conflicts of interest
      and favorable outcome. METHODS: Parallel-group RCTs with a binary primary outcome
      published in three general medical journals during 2013-2015 were identified. COI
      type, funding source, and outcome were extracted. Binomial logistic regression
      model was performed to assess association between COI and funding source with
      outcome. RESULTS: A total of 509 consecutive parallel-group RCTs were included in
      the study. COI was reported in 74% in mixed funded RCTs and in 99% in for-profit
      funded RCTs. Stock ownership was reported in none of the non-profit RCTs, in 7%
      of mixed funded RCTs, and in 50% of for-profit funded RCTs. Mixed-funded RCTs had
      employees from the funding company in 11% and for-profit RCTs in 76%.
      Multivariable logistic regression revealed that stock ownership in the funding
      company among any of the authors was associated with a favorable outcome (odds
      ratio = 3.53; 95% confidence interval = 1.59-7.86; p < 0.01). CONCLUSION: COI in
      for-profit funded RCTs is extensive, because the factors related to COI are not
      fully independent, a multivariable analysis should be cautiously interpreted.
      However, after multivariable adjustment only stock ownership from the funding
      company among authors is associated with a favorable outcome.

PMID- 28747227
TI  - High rhesus (Rh(D)) negative frequency and ethnic-group based ABO blood group
      distribution in Ethiopia.
AB  - BACKGROUND: Knowledge of the distribution of ABO-Rh(D) blood groups in a locality
      is vital for safe blood services. However, the distribution of these blood
      systems among Ethiopians in general is little explored. This study was,
      therefore, designed to determine the ABO-Rh(D) blood group distribution among
      patients attending Gambella hospital, southwestern Ethiopia. METHODS: A cross
      sectional study was conducted between November and December 2013 (N = 449). The
      patients were grouped into two broad categories. Those who originally moved from
      different parts of Ethiopia and currently residing in Gambella are named
      'highlanders' (n = 211). The other group consisted of natives (Nilotics) to the
      locality (n = 238). ABO-Rh(D) blood groups were typed by agglutination, open
      slide test method, using commercial antisera (Biotech laboratories Ltd, Ipswich,
      Suffolk, UK). RESULTS: Overall, majority of the participants (41.20%) had blood
      type 'O' followed by types 'A' (34.96%), 'B' (20.48%) and 'AB' (3.34%). However,
      blood type 'A' was the most frequent (44.07%) blood group among the 'highlanders'
      and 50.42% of Nilotic natives had type 'O'. The proportion of participants devoid
      of the Rh factor was 19.37%. CONCLUSIONS: While the ABO blood group distribution
      is similar to previous reports, the Rh(D) frequency is much higher than what was
      reported so far for Ethiopia and continental Africa.

PMID- 28747229
TI  - Vaginal metastasis as the initial presentation of leiomyosarcoma: a case report.
AB  - BACKGROUND: Uterine leiomyosarcomas are very rare and highly aggressive tumors
      that have a high rate of recurrence and poor prognosis, even when early
      diagnosed. Due to their relative rarity, there is limited research on optimal
      management strategies. CASE PRESENTATION: A 60-year-old woman with a history of
      an asymptomatic uterine leiomyoma presented in October 2015 with postmenopausal
      bleeding and a friable vaginal cyst that bled when palpated. A partial cystectomy
      was performed, and malignant-like cystic and solid components were identified.
      Histopathology diagnosed an unclassifiable malignant epithelioid tumor.
      Subsequent imaging studies identified a malignant uterine tumor, a metabolically
      active vaginal lesion, and two benign leiomyomas. An anterior pelvic exenteration
      (colpectomy, hysterectomy, bilateral adnexectomy, total cystectomy, and cutaneous
      ureteroileostomy ad modum Bricker) were performed by laparotomy in March 2016.
      Examination of the surgical specimens identified a 75 * 75-mm leiomyoma, an 80 *
      30-mm infiltrating mesenchymal uterine lesion with vascular invasion and tumor
      emboli, and a 60 * 30-mm perivascular vaginal tumor. Immunohistochemistry
      indicated a phenotypic transition from a uterine leiomyosarcoma to a vaginal
      epithelioid lesion; marker expression changed from the uterine tumor
      actin+/desmin+/caldesmon+/CD10- phenotype, through the tumor emboli, to an actin
      /desmin-/caldesmon-/CD10+ phenotype in the vaginal lesion. A high-grade uterine
      mesenchymal tumor and vaginal metastasis were diagnosed. Adjuvant chemotherapy
      with docetaxel, gemcitabine, and doxorubicin commenced in May 2016 and treatment
      has been well tolerated. CONCLUSIONS: Differentiating leiomyosarcoma from
      leiomyoma is challenging and few tools other than microscopic evaluation are
      available. Vaginal compromise in leiomyosarcoma usually results from tumor
      extension, not hematogenous metastasis. A vaginal metastasis is a very rare
      initial presentation. We have found only two cases like this described on
      published literature. The atypical clinical and histological presentation in our
      case complicated diagnosis and delayed treatment. An early diagnosis and complete
      surgical clearance gives the best chance of survival, and imaging tools should be
      applied early in instances of new suspicious malignant lesions.

PMID- 28747230
TI  - Full-length genome sequence analysis of enzootic nasal tumor virus isolated from
      goats in China.
AB  - BACKGROUND: Enzootic nasal tumor virus (ENTV) is a betaretrovirus of sheep (ENTV
      1) and goats (ENTV-2) associated with neoplastic transformation of epithelial
      cells of the ethmoid turbinate. Confirmation of the role of ENTV in the
      pathogenesis of enzootic nasal adenocarcinoma (ENA) has yet to be resolved due to
      the inability to culture the virus. Very little is known about the prevalence of
      this disease, particularly in China. METHODS: To evaluate the genetic diversity
      of ENTV-2 from Shaanxi province of China, the complete genome sequence of four
      isolates from Shaanxi province was determined by RT-PCR. These sequences were
      analyzed to evaluate their genetic relatedness with other small ruminant
      betaretroviruses. Phylogenetic analyses based on the gag gene and env gene were
      performed. RESULTS: The ENTV-2-Shaanxi1 genome shared 97.0% sequence identity
      with ENTV-2-SC (accession number HM104174.1), and 89.6% sequence identity with
      the ENTV-2 sequences (accession number AY197548.1). ENTV-2 is closely related to
      the ENTV-1 and jaagsiekte retrovirus (JSRV). The main sequence differences
      between these viruses reside in LTR, two small regions of Gag, Orf-x, and the
      transmembrane (TM) region of Env. A stretch of 6 consecutive proline residues
      exists in VR1 of the ENTV-2-Shaanxi1 ~ 4 isolates. All the ENTV-2-Shaanxi
      isolates have the YXXM motif in the cytoplasmic tail of the Env. Phylogenetic
      analysis by nucleotide sequences showed that ENTV-2-Shaanxi1 ~ 4 isolates were
      closest related to two ENTV-2 isolates published in NCBI, especially with ENTV-2
      SC strain. CONCLUSIONS: This finding indicates that ENA most likely was
      introduced to Shaanxi province by the movement of contaminated goats from other
      areas in China. This study adds to understand the circulation, variation and
      distribution of ENTV-2, and may prove beneficial in future control or eradication
      programmes.

PMID- 28747228
TI  - Iodine nutritional status of women in their first trimester of pregnancy in
      Catalonia.
AB  - BACKGROUND: Sufficient iodine intake is needed during pregnancy to ensure proper
      fetal development. The iodine levels of women in their first trimester of
      pregnancy in Catalonia are currently unknown. This data would help to determine
      whether our public health services should establish recommendations or
      interventions in this line. The aim of this study was to investigate the iodine
      nutritional status, prevalence of urinary iodine <150 MUg/L, and tobacco use in
      the first trimester of pregnancy in our setting. METHODS: Cross-sectional study.
      Data were collected during 2008-2009 from women in their first trimester at the
      primary care centers of the province of Barcelona (Spain). Pregnant women
      included in the study completed a questionnaire on eating habits and underwent
      urinary iodine concentration (UIC) assessment. RESULTS: Nine hundred forty five
      women completed the dietary questionnaire and urinary iodine testing. Median UIC
      was 172 MUg/L, with 407 participants (43.1%) showing levels <150 MUg/L. On
      multivariate logistic regression analysis, intake of 1-2 glasses of milk per day,
      OR = 0.636 95% CI (0.45-0.90) or >2 glasses, OR = 0.593 95% CI (0.37-0.95);
      iodized salt consumption, OR = 0.678 95% CI (0.51-0. 90); and use of iodine
      supplementation, OR = 0.410 95% CI (0.31-0.54), protected against the risk of UIC
      <150 MUg/L. Simultaneous consumption of iodized salt and milk (>=1 glass/day)
      showed a larger protective effect: OR = 0.427, 95% CI (0.31-0.54). CONCLUSION:
      The median UIC of the pregnant women surveyed indicated an acceptable iodine
      nutritional status according to the criteria established by the WHO and ICCIDD.
      The risk of urinary iodine <150 MUg/L decreased with simultaneous consumption of
      milk and iodized salt, similar to the decrease seen with iodine supplementation.

PMID- 28747231
TI  - Different patient satisfaction levels between the first and second knee in the
      early stage after simultaneous bilateral total knee arthroplasty (TKA): a
      comparison between subjective and objective outcome assessments.
AB  - BACKGROUND: Simultaneous bilateral total knee arthroplasty (TKA) is an effective
      treatment option and safe for properly selected patients. The purpose of this
      study was to evaluate whether patients have different satisfaction levels between
      the first and second knee in the early stage after simultaneous bilateral TKA.
      METHODS: We retrospectively reviewed 46 patients who underwent simultaneous
      bilateral TKA by a single surgeon in our department between March 2013 and March
      2015. The surgeon typically performed first-side TKA (right knee), followed by
      TKA on the left knee. Tranexamic acid (TXA) (10 mg/kg) was given intravenously,
      and the tourniquet was released after wound closure. The preoperative KSS, ROM,
      and pain visual analog scale (VAS); the objective parameters including drainage
      volume and swelling evaluated by the circumference of the 10 cm above the
      patella; and the preoperative and postoperative (1st, 3rd, and 7th days)
      subjective parameters including pain, satisfaction VAS, and patient satisfaction
      of the first and second surgeries for each knee were analyzed. RESULTS: In
      simultaneous bilateral TKA, compared with the second-side TKA (left knee), the
      first-side TKA (right knee) had a lower mean drainage volume (p < 0.05), but the
      swelling of the knee was higher on the 1st, 3rd, and 7th postoperative days (p <
      0.05). Moreover, the first-side TKA was scored lower in satisfaction VAS but
      higher in pain VAS at the 1st, 3rd, and 7th postoperative days. The patient
      satisfaction scores indicated 2 (4.4%) of the 46 patients scored first-side TKA
      higher than second-side TKA, 34 (73.9%) of the 46 patients scored second-side TKA
      higher than first-side TKA, and 10 (21.7%) of the 46 patients scored their
      satisfaction as the same for both knees. CONCLUSIONS: This research study found
      that there was better patient satisfaction with the second knee in the early
      stage after simultaneous bilateral TKA, which may provide some considerations for
      surgeons choosing simultaneous bilateral total knee arthroplasty for patients
      with osteoarthritis in both knees.

PMID- 28747232
TI  - Development of an accumulation assay and evaluation of the effects of efflux pump
      inhibitors on the retention of chlorhexidine digluconate in Pseudomonas
      aeruginosa and Staphylococcus aureus.
AB  - BACKGROUND: Chlorhexidine digluconate (CHG) is used as a disinfectant. The
      emergence of pathogens resistant to the biocide raises health concern.
      Information on specific efflux mechanisms utilised by bacteria to confer reduced
      susceptibility to the biocide, may be used to develop ways of preventing the
      efflux of the biocide from nosocomial pathogens resulting in higher disinfection
      activity. The aim of the study was to evaluate the role of ATP-binding cassette
      transporters on the transport of CHG in bacteria. METHODS: Clinical strains of
      Pseudomonas aeruginosa, Staphylococcus aureus and their respective laboratory
      strains ATCC 27853 and ATCC 9144 were used for susceptibility tests. The minimum
      inhibitory concentration (MIC) of CHG with or without an efflux pump inhibitor
      [reserpine or carbonyl cyanide m-chlorophenylhydrazone (CCCP)] was determined
      using the broth microdilution method. A spectrophotometric method to quantify the
      amount of chlorhexidine in a sample was developed, validated and used to quantify
      CHG within P. aeruginosa and S. aureus cells. RESULTS: In the presence of
      reserpine, the MIC of CHG against the clinical strains of P. aeruginosa and S.
      aureus decreased from 6.3 to 3.2 ug/ml but showed no change against both ATCC
      isolates. The MIC of CHG in the presence of CCCP for both strains of P.
      aeruginosa remained unchanged but showed a reduction for both isolates of S.
      aureus. The suitability of the spectrophotometric method developed for
      quantifying the amount of CHG accumulated in microbial cells was validated and
      used successfully to quantify CHG accumulated within bacterial cells. CONCLUSION:
      The spectrophotometric determination of CHG within microbial cells may be used to
      quantify CHG in microbial cells. Only the clinical strain of P. aeruginosa showed
      significant efflux of CHG suggesting the participation of efflux transporters in
      the pumping out of CHG from this isolate. The use of efflux pump inhibitors
      together with the biocide may be explored to preventing the efflux of the biocide
      from P. aeruginosa resulting in order to increase disinfection activity.

PMID- 28747233
TI  - Post-mating spermatophore storage strategies in two species of crayfish:
      implications for broodstock management.
AB  - Female crayfish stores male gametes after mating until the beginning of egg
      laying and fertilization. The aim of the present study was to investigate the
      duration of post-mating spermatophore storage as well as the timing and
      temperature of spawning in two crayfish species of economic importance, namely
      the signal crayfish Pacifastacus leniusculus and the noble crayfish Astacus
      astacus. Results showed that the average duration of the post-mating
      spermatophore storage is significantly (P<0.05) longer in the noble crayfish
      (34.6+/-1.7 days, range: 19 to 60 days) than the signal crayfish (3.9+/-0.5 days,
      range: 1 to 18 days). The highest percentages of the post-mating spermatophore
      storage duration in the signal crayfish (46.5%) and the noble crayfish (44.5%)
      were 1 and 31 to 40 days, respectively. While there is an overlap in the timings
      of mating and egg laying in the signal crayfish, these two reproductive processes
      were not observed at the same days in the noble crayfish and there was at least 2
      weeks interval between last mating and first egg laying individuals. Average
      mating and egg laying temperatures were significantly (P<0.05) higher in the
      signal crayfish than the noble crayfish. The average temperatures for mating in
      both species were significantly (P<0.05) higher than the temperatures that they
      utilized for egg laying. In conclusion, female noble crayfish stores post-mating
      spermatophores a longer duration compared with the signal crayfish. Also, the
      signal crayfish mates and lays egg in temperatures that are higher than the noble
      crayfish. Spawning season is shorter in the signal crayfish compared with the
      noble crayfish. The results of present study provide information contributing to
      the crayfish broodstock management in aquaculture.

PMID- 28747234
TI  - Integrating multiple criteria for the characterization of Psammotettix
      populations in European cereal fields.
AB  - The wheat dwarf disease is among the most damaging diseases in cereals. Its
      aetiological agent is the Wheat dwarf virus (WDV), which is exclusively
      transmitted from plant to plant by leafhoppers from the genus Psammotettix
      (Hemiptera, Cicadellidae). The parameters linked to the WDV/Psammotettix
      pathosystem are still poorly understood. We studied Psammotettix individuals
      collected in wheat and barley fields in France and, as a comparison, from
      grassland at agroecological interface in West Slovenia. Species identity of males
      and females has been determined using multiple criteria. In the first step, the
      characterization of the collected individuals included recordings of vibrational
      signals used in mating behaviour and morphometric analyses. In addition, a 442 nt
      sequence of the mitochondrial cytochrome oxydase I (COI) gene was obtained for
      some individuals and compared to COI sequences of the Psammotettix leafhoppers
      available in public databases. In the cereal fields in France, P sammotettix
      alienus was the most numerous species; however, it sometimes occurred together
      with Psammotettix confinis, while in the grasslands in Slovenia, the third
      syntopic species in Psammotettix community was Psammotettix helvolus. The
      temporal parameters of the P. alienus male calling song that were measured in
      this study were very similar to those measured in a previous study. The local
      biotic and/or abiotic parameters most likely influence the life history of
      Psammotettix leafhoppers, and the proportion of viruliferous individuals
      collected in cereal fields was 14.9%, while leafhoppers collected in Slovenia
      were virus-free. Taken together, results show that more detailed information on
      population structure of Psammotettix leafhoppers is crucial for providing an
      insight into the epidemiology of wheat dwarf disease.

PMID- 28747235
TI  - Journalists' Occupational Stress: A Comparative Study between Reporting Critical
      Events and Domestic News.
AB  - Nowadays, journalism is considered a stressful occupation, not only due to the
      stress perceived in journalists' daily work but also due to the critical,
      potentially traumatic events they report. However, research on journalists'
      occupational stress in both these professional settings is still scarce. This
      study aims to characterize and compare occupational stress variables perceived by
      journalists in their daily work and in critical scenarios. Taking the Holistic
      Model of Occupational Stress by Nelson and Simmons (2003) as a framework, 25
      Portuguese journalists, all with experience in reporting critical events, were
      interviewed on their perceptions of some core variables of the model:
      occupational stressors, distress and eustress emotional reactions, and the
      consequences of these experiences on their well-being. Differences among these
      core variables, according to the number of deployments to a critical event, were
      statistically analysed in order to ascertain whether repeated exposure to trauma
      influenced journalists' occupational stress perceptions. The data content
      analysis showed that occupational stressors and emotional reactions differed
      across settings, while the consequences associated with journalists' experiences
      were perceived as being mainly negative in both occupational contexts.
      Significant differences were identified in some of these variables according to
      the number of deployments to a critical event (p < .05). These findings may
      contribute to a reflection on the role of media organizations in preparing and
      supporting journalists in their work performance, and on the promotion of
      occupational health within the scope of journalists' daily work and critical
      events. The article closes with considerations for future studies.

PMID- 28747236
TI  - Broadening End-of-Life Comfort to Improve Palliative Care Practices in Long Term
      Care.
AB  - This study aimed to (1) explore how palliative care in long-term care (LTC)
      addresses the tensions associated with caring for the living and dying within one
      care community, and (2) to inform how palliative care practices may be improved
      to better address the needs of all residents living and dying in LTC as well as
      those of the families and support staff. This article reports findings from 19
      focus groups and 117 participants. Study findings reveal that LTC home staff,
      resident, and family perspectives of end-of-life comfort applied to those who
      were actively dying and to their families. Our findings further suggest that
      eliciting residents' perceptions of end-of-life comfort, sharing information
      about a fellow resident's death more personally, and ensuring that residents,
      families, and staff can constructively participate in providing comfort care to
      dying residents could extend the purview of end-of-life comfort and support
      expanded integration of palliative principles within LTC.

PMID- 28747237
TI  - Mental health care utilisation among internally displaced persons in Ukraine:
      results from a nation-wide survey.
AB  - : Aims There are an estimated 1.5 million internally displaced persons (IDPs) in
      Ukraine because of the armed conflict in the east of the country. The aim of this
      paper is to examine utilisation patterns of mental health and psychosocial
      support (MHPSS) care among IDPs in Ukraine. METHODS: A cross-sectional survey
      design was used. Data were collected from 2203 adult IDPs throughout Ukraine
      between March and May 2016. Data on mental health care utilisation were
      collected, along with outcomes including post-traumatic stress disorder (PTSD),
      depression and anxiety. Descriptive and multivariate regression analyses were
      used. RESULTS: PTSD prevalence was 32%, depression prevalence was 22%, and
      anxiety prevalence was 17%. Among those that likely required care (screened
      positive with one of the three disorders, and also self-reporting a problem)
      there was a large treatment gap, with 74% of respondents who likely required
      MHPSS care over the past 12 months not receiving it. For the 26% (N = 180) that
      had sought care, the most common sources of services/support were pharmacies,
      family or district doctor/paramedic (feldsher), neurologist at a polyclinic,
      internist/neurologist at a general hospital, psychologists visiting communities,
      and non-governmental organisations/volunteer mental health/psychosocial centres.
      Of the 180 respondents who did seek care, 163 could recall whether they had to
      pay for their care. Of these 163 respondents, 72 (44%) recalled paying for the
      care they received despite government care officially being free in Ukraine. The
      average costs they paid for care was US$107 over the previous 12 months. All 180
      respondents reported having to pay for medicines and the average costs for
      medicines was US$109 over the previous 12 months. Among the 74% had not sought
      care despite likely needing it; the principal reasons for not seeking care were:
      thought that they would get better by using their own medications, could not
      afford to pay for health services or medications, no awareness of where to
      receive help, poor understanding by health care providers, poor quality of
      services, and stigma/embarrassment. The findings from multivariate regression
      analysis show the significant influence of a poor household economic situation on
      not accessing care. CONCLUSIONS: The study highlights a high burden of mental
      disorders and large MHPSS treatment gap among IDPs in Ukraine. The findings
      support the need for a scaled-up, comprehensive and trauma-informed response to
      provision of MHPSS care of IDPs in Ukraine alongside broader health system
      strengthening.

PMID- 28747238
TI  - Exploratory factor analysis and reliability of the Primary Health Care Engagement
      (PHCE) Scale in rural and remote nurses: findings from a national survey.
AB  - : Aim The study purpose was to provide evidence of validity for the Primary
      Health Care Engagement (PHCE) Scale, based on exploratory factor analysis and
      reliability findings from a large national survey of regulated nurses residing
      and working in rural and remote Canadian communities. BACKGROUND: There are
      currently no published provider-level instruments to adequately assess delivery
      of community-based primary health care, relevant to ongoing primary health care
      (PHC) reform strategies across Canada and elsewhere. The PHCE Scale reflects a
      contemporary approach that emphasizes community-oriented and community-based
      elements of PHC delivery. METHODS: Data from the pan-Canadian Nursing Practice in
      Rural and Remote Canada II (RRNII) survey were used to conduct an exploratory
      factor analysis and evaluate the internal consistency reliability of the final
      PHCE Scale. Findings The RRNII survey sample included 1587 registered nurses,
      nurse practitioners, licensed practical nurses, and registered psychiatric nurses
      residing and working in rural and remote Canada. Exploratory factor analysis
      identified an eight-factor structure across 28 items overall, and good internal
      consistency reliability was indicated by an alpha estimate of 0.89 for the final
      scale. The final 28-item PHCE Scale includes three of four elements in a
      contemporary approach to PHC (accessibility/availability, community
      participation, and intersectoral team) and most community-oriented/based elements
      of PHC (interdisciplinary collaboration, person-centred, continuity, population
      orientation, and quality improvement). We recommend additional psychometric
      testing in a range of health care providers and settings, as the PHCE Scale shows
      promise as a tool for health care planners and researchers to test interventions
      and track progress in primary health care reform.

PMID- 28747239
TI  - Palaeoparasitology and palaeogenetics: review and perspectives for the study of
      ancient human parasites.
AB  - While some species of parasites can be identified to species level from
      archaeological remains using microscopy (i.e. Enterobius vermicularis, Clonorchis
      sinensis), others can only be identified to family or genus level as different
      species produce eggs with similar morphology (i.e. Taenia sp. and Echinococcus
      sp.). Molecular and immunological approaches offer the possibility to provide
      more precise determination at the species level. They can also identify taxa when
      classic parasite markers such as eggs or cysts have been destroyed over time.
      However, biomolecules can be poorly preserved and modern reference DNA is
      available only for a limited number of species of parasites, leading to the
      conclusion that classic microscopic observation should be combined with molecular
      analyses. Here we present a review of the molecular approaches used over the past
      two decades to identify human pathogenic helminths (Ascaris sp., Trichuris sp.,
      E. vermicularis, Fasciola sp. etc.) or protists (Giardia sp., Trypanosoma sp.,
      Leishmania sp. etc.). We also discuss the prospects for studying the evolution of
      parasites with genetics and genomics.

PMID- 28747240
TI  - Signatures of mito-nuclear discordance in Schistosoma turkestanicum indicate a
      complex evolutionary history of emergence in Europe.
AB  - High levels of molecular diversity were identified in mitochondrial cytochrome c
      oxidase (cox1) gene sequences of Schistosoma turkestanicum from Hungary. These
      cox1 sequences were all specific to Hungary which contrasted with the low levels
      of diversity seen in the nuclear internal transcribed spacer region (ITS)
      sequences, the majority of which were shared between China and Iran isolates.
      Measures of within and between host molecular variation within S. turkestanicum
      showed there to be substantial differences in molecular diversity, with cox1
      being significantly more diverse than the ITS. Measures of haplotype frequencies
      revealed that each host contained its own subpopulation of genetically unique
      parasites with significant levels of differentiation. Pairwise mismatch analysis
      of cox1 sequences indicated S. turkestanicum populations to have a bimodal
      pairwise difference distribution and to be stable unlike the ITS sequences, which
      appeared to have undergone a recent population expansion event. Positive
      selection was also detected in the cox1 sequences, and biochemical modelling of
      the resulting protein illustrated significant mutational events causing an
      alteration to the isoelectric point of the cox1 protein, potentially altering
      metabolism. The evolutionary signature from the cox1 indicates local adaptation
      and long establishment of S. turkestanicum in Hungary with continual
      introgression of nuclear genes from Asian isolates. These processes have led to
      the occurrence of mito-nuclear discordance in a schistosome population.

PMID- 28747241
TI  - Developing a predictive model for the energy content of goat milk as the basis
      for a functional unit formulation to be used in the life cycle assessment of
      dairy goat production systems.
AB  - Recent reports on livestock environmental impact based on life cycle assessment
      (LCA) did not fully consider the case of the dairy goat. Assignment of an
      environmental impact (e.g. global warming potential) to a specific product needs
      to be related to the appropriate 'unitary amount' or functional unit (FU). For
      milk, the energy content may provide a common basis for a definition of the FU.
      To date, no ad hoc formulations for the FU of goat milk have been proposed. For
      these reasons, this study aimed to develop and test one or more predictive models
      (DPMs) for the gross energy (GE) content of goat milk, based on published
      compositional data, such as fat (F), protein, total solids (TS), solid non-fat
      matter (SNF), lactose (Lac) and ash. The DPMs were developed, selected and tested
      using a linear regression approach, as a meta-analysis (i.e. meta-regression) was
      not applicable. However, in the final stage, a control procedure for spurious
      findings was carried out using a Monte Carlo permutation test. Because several
      published predictive models (PPMs) for GE in cow milk and goat milk were found in
      the literature, they were tested on the same data set with which the DPMs were
      developed. The best-performing DPMs and PPMs were compared directly with a subset
      of the individual data retrieved from the literature. Overall, the paucity of
      direct measurements of the GE in goat milk was a limiting factor in collecting
      data from the literature; thus, only a small data set (n=26) was established,
      even though it was considered sufficiently representative of milks from different
      goat breeds. The three best PPMs based on F alone gave more biased estimates of
      the GE content of the goat milk than the three new DPMs based on F, F and SNF and
      F and TS, respectively. Accordingly, three different formulations of FU are
      proposed, depending on the availability of data including both F and TS (or F and
      SNF) or F alone. Even though several metrics can be used in defining the FU for
      milk to be used in LCAs of goat farming systems, the proposed FU formulations
      should be adopted in place of the similar energy-based ones developed for other
      dairy species.

PMID- 28747242
TI  - Identification and characterization of ace1-type acetylcholinesterase in
      insecticide-resistant and -susceptible Propylaea japonica (Thunberg).
AB  - Characterization and gene cloning of acetylecholinesterase (AChE) in the
      insecticide-resistant (R) and -susceptible (S) insects have been reported in the
      past. However, the studies focused mostly on herbivorous pests, rather than
      predacious species, such as ladybird beetles. Using R and S Propylaea japonica
      (thunberg), a full-length cDNA sequence (2928 bp) of the ace1-type AChE gene was
      determined for the first time. The ace1 encoding a protein of 645 amino acids
      contained typical conserved motifs, such as FGESAG domains, catalytic triad, acyl
      pocket, oxyanino hole, choline binding site, peripheral anionic site, omega loop
      and conserved aromatic residues. R P. japonica displayed 50-times greater
      resistance to chlorpyrifos or mathamidophos with a significantly lower AChE
      sensitivity to paraoxon, malaoxon, chlorpyrifos or methamidophos than its S
      counterpart. Five amino acids in the ace1 of R P. japonica differed from those
      found in S P. japonica. One of them, F358S, located in the acyl-binding pocket,
      might play a crucial role in the resistance of the insect to organophosphates
      (OPs). Whereas, K493E and I538V, which were close to some of the conserved
      aromatic amino acids (i.e., H509, Y511, and W499) in the gorge, and G571R and
      T576A near C593 that formed the disulfide bonds with C471, might also involve in
      the change of insecticide resistance in P. japonica. AChE insensitivity and amino
      acid replacements, particularly F358S, might be the determining factors in the
      alteration of OPs-resistance in P. japonica.

PMID- 28747243
TI  - Relative reticulo-rumen pH indicators for subacute ruminal acidosis detection in
      dairy cows.
AB  - Subacute ruminal acidosis (SARA) is usually characterized by abnormal and
      intermittent drops in rumen pH. Nevertheless, high individual animal variability
      in rumen pH and the difference in measurement methods for pH data acquisition
      decrease the sensitivity and accuracy of pH indicators for detecting SARA in
      ruminants. The aim of this study was to refine rumen pH indicators in long-term
      SARA based on individual dairy cow reticulo-rumen pH kinetics. Animal
      performances and rumen parameters were studied weekly in order to validate SARA
      syndrome and rumen pH was continuously measured using reticulo-rumen sensors. In
      total, 11 primiparous dairy cows were consecutively fed two different diets for
      12 successive weeks: a control diet as low-starch diet (LSD; 13% starch for 4
      weeks in period 1), an acidotic diet as high-starch diet (HSD; 32% starch for 4
      weeks in period 2), and again the LSD diet (3 weeks in period 3). There was a 1
      week dietary transition between LSD and HSD. Commonly used absolute SARA pH
      indicators such as daily average, area under the curve (AUC) and time spent below
      pH<5.8 and pH<6 were processed from absolute (raw) daily kinetics. Then signal
      processing was applied to raw pH values in order to calculate relative pH
      indicators by filtering and normalizing data to remove inter-individual
      variability, sensor drift and sensor noise. Normalized AUC, times spent below
      NpH<-0.3 and NpH<-0.5, NpH range and NpH standard deviation were calculated.
      Those relative pH indicators were compared with commonly used pH indicators to
      assess their ability to detect SARA. This syndrome induced by HSD was confirmed
      by consistent expected changes in milk quality, dry matter intake and acetate :
      propionate ratio in the rumen, whereas the ruminal concentration of
      lipopolysaccharide was increased. Commonly used pH SARA indicators were not able
      to discriminate SARA syndrome due to high animal variability and sensor drift and
      noise, whereas relative pH indicators developed in this study appeared more
      relevant for SARA detection as assessed by receiver operating characteristic
      tests. This work shows that absolute pH kinetics should be corrected for drift,
      noise and animal variability to produce relative pH indicators that are more
      robust for SARA detection. These relative pH indicators could be more relevant
      for identifying affected animals in a herd and also for comparing SARA risk among
      studies.

PMID- 28747244
TI  - Are nurses meeting the needs of men in primary care?
AB  - Meeting men's health needs by improving healthcare service access is a key
      objective of comprehensive primary health care. The aims of this qualitative
      study were to explore the perception of nurses in men's health services and to
      describe men's expectation of the nurse. The comparative component identifies the
      barriers and facilitators to improved access to health services. A purposive
      sample of 19 nurses and 20 men was recruited from metropolitan and regional
      settings in the state of Victoria, Australia, and each participant was
      interviewed individually or as part of three focus groups. The main findings
      were: nurses and men were unclear on the role of the nurse in men's health; and
      health promotion provided by nurses was predominantly opportunistic. Both
      participant groups indicated barriers to healthcare access related to: the
      culture and environment in general practice; limitation of Australia's Medicare
      healthcare financing system; out-of-pocket costs, waiting time and lack of
      extended hours; and men not wanting to be perceived as complainers. Facilitators
      related to: positive inter-professional relations; effective communication;
      personal qualities; and level of preparedness of nurse education. The findings
      demonstrate a need for the role to be better understood by both men and nurses in
      order to develop alternative approaches to meeting men's healthcare needs.

PMID- 28747245
TI  - Utilisation of Medicare-funded schemes for people with cardiovascular disease.
AB  - The aim of this study is to investigate the utilisation of Medicare Benefit
      Scheme items for chronic disease in the management of cardiovascular disease
      (CVD) in general practice and to compare characteristics of CVD patients with and
      without a General Practice Management Plan (GPMP). Subgroup analysis of Treatment
      of Cardiovascular Risk using Electronic Decision Support (TORPEDO) baseline data
      was collected in a cohort comprising 6123 patients with CVD. The mean age (s.d.)
      was 71 (+/-13) years, 55% were male, 64% had a recorded diagnosis of coronary
      heart disease, 31% also had a diagnosis of diabetes and the mean number of
      general practice (GP) visits (s.d.) was 11 (+/-9) in 12 months. A total of
      1955/6123 (32%) received a GPMP in the 12 months before data extraction; 1%
      received a Mental Health Plan. Factors associated with greater likelihood of
      receiving a GPMP were: younger age, had a diagnosis of diabetes, BMI > 30kgm-2,
      prescription of blood pressure-lowering therapy and more than ten general
      practice visits. Enhancing utilisation of existing schemes could augment
      systematic follow up and support of patients with CVD.

PMID- 28747246
TI  - Emergency department crowding and sepsis.

PMID- 28747247
TI  - Intravenous fish oil in critically ill and surgical patients - Historical remarks
      and critical appraisal.
AB  - The purpose of this review is to explain the historical and clinical background
      for intravenous fish oil administration, to evaluate its results by using a
      product specific metaanalysis, and to stimulate further research in the immune
      modulatory potential of fish oil. Concerning the immune-modulatory effects of
      fatty acids, a study revealed that omega-3 as well as omega-6 fatty acids would
      prolong transplant survival, and only a mixture with an omega-6:omega-3 ratio of
      2.1:1 would give immune-neutral results. In 1998, the label of a newly registered
      fish oil emulsion also acknowledged this immune-neutral ratio in conjunction with
      omega-6 lipids. Also, two fish oil-supplemented fat emulsions, registered in
      2004, used a similar omega-6:omega-3 ratio. Such an immune-neutral omega-6:omega
      3 ratio denoted progress for most patients compared to pure omega-6 lipid
      emulsions. However, this immune-neutrality might on the other hand be responsible
      for the limited positive clinical results gained so far in critically ill and
      surgical patients where in most cases significance could only be shown for the
      pooled effect of numerous trials. Our product specific metaanalysis also did not
      reveal any differences, neither in infections rates nor in ICU or hospital length
      of stay. To evaluate the immune-modulatory effect of fish oil administered alone,
      new dose finding studies, reporting relevant clinical outcome parameters, are
      required. Precise mechanistic or physiological biomarkers for the indication of
      such a therapy should also be developed and validated.

PMID- 28747248
TI  - Pathways between childhood/adolescent adversity, adolescent socioeconomic status,
      and long-term cardiovascular disease risk in young adulthood.
AB  - OBJECTIVE: The current study investigated mediators between childhood/adolescent
      adversities (e.g., dating violence, maltreatment, homelessness, and parental
      death), low socioeconomic status (SES) during adolescence, and cardiovascular
      disease (CVD) risk in young adulthood. The purpose of these analyses was to
      understand whether SES during adolescence and childhood/adolescent adversities
      affect CVD risk through similar pathways, including maternal relationship
      quality, health behaviors, financial stress, medical/dental care, educational
      attainment, sleep problems, and depressive symptoms. METHODS: Using the National
      Longitudinal Study of Adolescent to Adult Health (N = 14,493), which has followed
      US adolescents (Wave 1; M = 15.9 years) through early adulthood (Wave 4; M = 28.9
      years), associations were examined between childhood/adolescent adversity and SES
      to 30-year CVD risk in young adulthood. The outcome was a Framingham-based
      prediction model of CVD risk that included age, sex, body mass index, smoking,
      systolic blood pressure, diabetes, and antihypertensive medication use at Wave 4.
      Path analysis was used to examine paths through the adolescent maternal
      relationship to young adult mediators of CVD risk. RESULTS: Childhood/adolescent
      adversity significantly predicted greater adult CVD risk through the following
      pathways: maternal relationship, health behaviors, financial stress, lack of
      medical/dental care, and educational attainment; but not through depressive
      symptoms or sleep problems. Lower SES during adolescence significantly predicted
      greater adult CVD risk through the following pathways: health behaviors,
      financial stress, lack of medical/dental care, and educational attainment, but
      not maternal relationship, depressive symptoms, or sleep problems. CONCLUSIONS:
      Childhood/adolescent adversities and SES affected CVD risk in young adulthood
      through both similar and unique pathways that may inform interventions.

PMID- 28747249
TI  - Surrogacy of progression-free survival (PFS) for overall survival (OS) in
      esophageal cancer trials with preoperative therapy: Literature-based meta
      analysis.
AB  - BACKGROUND: There have been no reports evaluating progression-free survival (PFS)
      as a surrogate endpoint in resectable esophageal cancer. This study was conducted
      to evaluate the trial level correlations between PFS and overall survival (OS) in
      resectable esophageal cancer with preoperative therapy and to explore the
      potential benefit of PFS as a surrogate endpoint for OS. METHODS: A systematic
      literature search of randomized trials with preoperative chemotherapy or
      preoperative chemoradiotherapy for esophageal cancer reported from January 1990
      to September 2014 was conducted using PubMed and the Cochrane Library. Weighted
      linear regression using sample size of each trial as a weight was used to
      estimate coefficient of determination (R2) within PFS and OS. The primary
      analysis included trials in which the HR for both PFS and OS was reported. The
      sensitivity analysis included trials in which either HR or median survival time
      of PFS and OS was reported. In the sensitivity analysis, HR was estimated from
      the median survival time of PFS and OS, assuming exponential distribution.
      RESULTS: Of 614 articles, 10 trials were selected for the primary analysis and 15
      for the sensitivity analysis. The primary analysis did not show a correlation
      between treatment effects on PFS and OS (R2 0.283, 95% CI [0.00-0.90]). The
      sensitivity analysis did not show an association between PFS and OS (R2 0.084,
      95% CI [0.00-0.70]). CONCLUSION: Although the number of randomized controlled
      trials evaluating preoperative therapy for esophageal cancer is limited at the
      moment, PFS is not suitable for primary endpoint as a surrogate endpoint for OS.

PMID- 28747250
TI  - Normal neuroanatomical variants that may be misinterpreted as disease entities.
AB  - Variations of normal development and benign incidental anomalies are frequently
      observed on diagnostic neuroimaging. It is important these are recognised for
      what they are, as misinterpretation may result in unnecessary further
      investigation, follow-up imaging and anxiety. In this article, we review benign
      intracranial anomalies commonly referred to our unit for specialist
      neuroradiology advice or multidisciplinary discussion, concerning cysts of the
      pineal gland and pituitary fossa, vascular anomalies, and perivascular spaces.
      This article outlines the embryology and development, the various imaging
      features as well as the clinical relevance and differential diagnoses of each
      normal neuroanatomical variant.

PMID- 28747252
TI  - Analysis of the tractive force pattern on a knot by force measurement during
      laparoscopic knot tying.
AB  - BACKGROUND: Quantifying surgical skills assists novice surgeons when learning
      operative techniques. We measured the interaction force at a ligation point and
      clarified the features of the force pattern among surgeons with different skill
      levels during laparoscopic knot tying. METHODS: Forty-four surgeons were divided
      into three groups based on experience: 13 novice (0-5 years), 16 intermediate (6
      15 years), and 15 expert (16-30 years). To assess the tractive force direction
      and volume during knot tying, we used a sensor that measures six force-torque
      values (x-axis: Fx, y-axis: Fy, z-axis: Fz, and xy-axis: Fxy) attached to a slit
      Penrose drain. All participants completed one double knot and five single knot
      sequences. We recorded completion time, force volume (FV), maximum force (MF),
      time over 1.5 N, duration of non-zero force, and percentage time when vertical
      force exceeded horizontal force (PTz). RESULTS: There was a significant
      difference between groups for completion time (p = 0.007); FV (total: p = 0.002;
      Fx: p = 0.004, Fy: p = 0.007, Fxy: p = 0.004, Fz: p < 0.001, Fxy/Fz: p = 0.003),
      MF (total: p = 0.004; Fx: p = 0.015, Fy: p = 0.035, Fxy: p = 0.009, Fz: p =
      0.001, Fxy/Fz: p = 0.041); time over 1.5 N (p = 0.002); duration of non-zero
      force (p = 0.029); and PTz (p < 0.001). PTz showed the only significant
      difference comparing intermediates with experts (intermediates: 13.7 +/- 9.0,
      experts: 4.9 +/- 3.2; p < 0.001). CONCLUSIONS: We clarified the characteristics
      of the force pattern at the ligation point during suturing by surgeons with three
      levels of experience using a force measurement system. We revealed that both
      force volume and force direction differed depending on surgeons' skill level
      during knot tying.

PMID- 28747251
TI  - SERCA control of cell death and survival.
AB  - Intracellular calcium (Ca2+) is a critical coordinator of various aspects of
      cellular physiology. It is increasingly apparent that changes in cellular Ca2+
      dynamics contribute to the regulation of normal and pathological signal
      transduction that controls cell growth and survival. Aberrant perturbations in
      Ca2+ homeostasis have been implicated in a range of pathological conditions, such
      as cardiovascular diseases, diabetes, tumorigenesis and steatosis hepatitis.
      Intracellular Ca2+ concentrations are therefore tightly regulated by a number of
      Ca2+ handling enzymes, proteins, channels and transporters located in the plasma
      membrane and in Ca2+ storage organelles, which work in concert to fine tune a
      temporally and spatially precise Ca2+ signal. Chief amongst them is the
      sarco/endoplasmic reticulum (SR/ER) Ca2+ ATPase pump (SERCA) which actively re
      accumulates released Ca2+ back into the SR/ER, therefore maintaining Ca2+
      homeostasis. There are at least 14 different SERCA isoforms encoded by three
      ATP2A1-3 genes whose expressions are species- and tissue-specific. Altered SERCA
      expression and activity results in cellular malignancy and induction of ER stress
      and ER stress-associated apoptosis. The role of SERCA misregulation in the
      control of apoptosis in various cell types and disease setting with prospective
      therapeutic implications is the focus of this review. Ca2+ is a double edge sword
      for both life as well as death, and current experimental evidence supports a
      model in which Ca2+ homeostasis and SERCA activity represent a nodal point that
      controls cell survival. Pharmacological or genetic targeting of this axis
      constitutes an incredible therapeutic potential to treat different diseases
      sharing similar biological disorders.

PMID- 28747253
TI  - Ordered mesoporous carbon as sorbent for the extraction of N-nitrosamines in
      wastewater and swimming pool water.
AB  - The analysis and determination of N-nitrosamines (NAs) in water samples are
      challenging and demanding. In this study, a simple, reliable, and practical
      methodology is reported for the quantitative determination by gas chromatography
      tandem mass spectrometry with electron impact ionization (EI) and triple
      quadrupole analyzer (GC-EI-MS/MS) of eight NAs after micro-solid-phase extraction
      (MU-SPE) from wastewater and swimming pool water. Thirty milligram of an ordered
      mesoporous carbonaceous material, oxidative surface-modified CMK-3, enclosed
      within a porous polypropylene membrane bag, were used as sorbent for MU-SPE. A
      central composite design approach was applied to optimize the MU-SPE parameters.
      An isotopically-labeled NA was used as internal standard. Under the optimized
      conditions, MU-SPE-GC-EI-MS/MS was validated for an NA concentration range of
      between 0.1-100ng/mL. The precision of the method was evaluated and an average
      relative standard deviation of 4.8% (n=8) for a standard solution spiked at
      50ng/mL of each NA was obtained. The limits of detection were measured to be in
      the range of 0.005-0.283ng/mL. Domestic wastewater and swimming pool water
      samples were used to evaluate the applicability of the method. NAs were detected
      in swimming pool water and wastewater at concentrations of <2ng/mL and 11ng/mL,
      respectively.

PMID- 28747254
TI  - Simulation of elution profiles in liquid chromatography - II: Investigation of
      injection volume overload under gradient elution conditions applied to second
      dimension separations in two-dimensional liquid chromatography.
AB  - An important research direction in the continued development of two-dimensional
      liquid chromatography (2D-LC) is to improve the detection sensitivity of the
      method. This is especially important in applications where injection of large
      volumes of effluent from the first dimension (1D) column into the second
      dimension (2D) column leads to severe 2D peak broadening and peak shape
      distortion. For example, this is common when coupling two reversed-phase columns
      and the organic solvent content of the 1D mobile phase overwhelms the 2D column
      with each injection of 1D effluent, leading to low resolution in the second
      dimension. In a previous study we validated a simulation approach based on the
      Craig distribution model and adapted from the work of Czok and Guiochon [1] that
      enabled accurate simulation of simple isocratic and gradient separations with
      very small injection volumes, and isocratic separations with mismatched injection
      and mobile phase solvents [2]. In the present study we have extended this
      simulation approach to simulate separations relevant to 2D-LC. Specifically, we
      have focused on simulating 2D separations where gradient elution conditions are
      used, there is mismatch between the sample solvent and the starting point in the
      gradient elution program, injection volumes approach or even exceed the dead
      volume of the 2D column, and the extent of sample loop filling is varied. To
      validate this simulation we have compared results from simulations and
      experiments for 101 different conditions, including variation in injection volume
      (0.4-80MUL), loop filling level (25-100%), and degree of mismatch between sample
      organic solvent and the starting point in the gradient elution program (-20 to
      +20% ACN). We find that that the simulation is accurate enough (median errors in
      retention time and peak width of -1.0 and -4.9%, without corrections for extra
      column dispersion) to be useful in guiding optimization of 2D-LC separations.
      However, this requires that real injection profiles obtained from 2D-LC interface
      valves are used to simulate the introduction of samples into the 2D column. These
      profiles are highly asymmetric - simulation using simple rectangular pulses leads
      to peak widths that are far too narrow under many conditions. We believe the
      simulation approach developed here will be useful for addressing practical
      questions in the development of 2D-LC methods.

PMID- 28747255
TI  - Adjuvant gemcitabine-docetaxel chemotherapy for stage I uterine leiomyosarcoma:
      Trends and survival outcomes.
AB  - OBJECTIVE: To assess recent trends of administering adjuvant gemcitabine
      docetaxel (GD) chemotherapy for Stage I uterine leiomyosarcoma, and to compare
      disease-free and overall survival between women who received and did not receive
      adjuvant GD chemotherapy. METHODS: All patients diagnosed with Stage I uterine
      leiomyosarcoma in a California-Colorado population-based health plan inclusive of
      2006-2013 were included in a retrospective cohort. Adjuvant GD chemotherapy
      rates, clinico-pathologic characteristics and survival estimates were assessed.
      RESULTS: Of 111 women with Stage I uterine leiomyosarcoma, 33 received adjuvant
      GD (median 4cycles), 77 received no chemotherapy, and 1 patient excluded for non
      GD chemotherapy. GD-chemotherapy and no-chemotherapy groups were similar with
      respect to age, stage (IA/IB), uterine weight, mitotic index, body mass index,
      and Charlson comorbidity score. Non-Hispanic white women were twice as likely to
      receive adjuvant chemotherapy as non-white or Hispanic women (37.7 vs. 17.1%,
      P=0.02). The proportion of women receiving adjuvant GD chemotherapy increased
      from 6.5% in 2006-2008 to 46.9% in 2009-2013 (P<0.001). There was no significance
      difference in unadjusted Kaplan-Meyer estimated disease-free (P=0.95) or overall
      survival (P=0.43) between GD-chemotherapy and no-chemotherapy cohorts.
      Corresponding adjusted Cox proportional hazard ratios for adjuvant GD
      chemotherapy compared to no chemotherapy were 1.01 (95% confidence interval [CI]
      0.57-1.80, P=0.97) for recurrence and 1.28 (95% CI 0.69-2.36, P-0.48) for
      mortality. CONCLUSIONS: Use of adjuvant GD chemotherapy for Stage I uterine
      leiomyosarcoma has increased significantly in the last decade, despite unclear
      benefit. Compared to no chemotherapy, 4-6cycles of adjuvant GD chemotherapy does
      not appear to alter survival outcomes.

PMID- 28747256
TI  - Electronic clinical decision support system and multifactorial risk factor
      control in patients with type 2 diabetes in primary health care.

PMID- 28747257
TI  - Cells with Treg-specific FOXP3 demethylation but low CD25 are prevalent in
      autoimmunity.
AB  - Identification of alterations in the cellular composition of the human immune
      system is key to understanding the autoimmune process. Recently, a subset of
      FOXP3+ cells with low CD25 expression was found to be increased in peripheral
      blood from systemic lupus erythematosus (SLE) patients, although its functional
      significance remains controversial. Here we find in comparisons with healthy
      donors that the frequency of FOXP3+ cells within CD127lowCD25low CD4+ T cells
      (here defined as CD25lowFOXP3+ T cells) is increased in patients affected by
      autoimmune disease of varying severity, from combined immunodeficiency with
      active autoimmunity, SLE to type 1 diabetes. We show that CD25lowFOXP3+ T cells
      share phenotypic features resembling conventional CD127lowCD25highFOXP3+ Tregs,
      including demethylation of the Treg-specific epigenetic control region in FOXP3,
      HELIOS expression, and lack of IL-2 production. As compared to conventional
      Tregs, more CD25lowFOXP3+HELIOS+ T cells are in cell cycle (33.0% vs 20.7% Ki
      67+; P = 1.3 * 10-9) and express the late-stage inhibitory receptor PD-1 (67.2%
      vs 35.5%; P = 4.0 * 10-18), while having reduced expression of the early-stage
      inhibitory receptor CTLA-4, as well as other Treg markers, such as FOXP3 and
      CD15s. The number of CD25lowFOXP3+ T cells is correlated (P = 3.1 * 10-7) with
      the proportion of CD25highFOXP3+ T cells in cell cycle (Ki-67+). These findings
      suggest that CD25lowFOXP3+ T cells represent a subset of Tregs that are derived
      from CD25highFOXP3+ T cells, and are a peripheral marker of recent Treg expansion
      in response to an autoimmune reaction in tissues.

PMID- 28747258
TI  - Confidence and clinical judgement in community nurses managing venous leg
      ulceration - A judgement analysis.
AB  - BACKGROUND: The variation in the management of venous leg ulceration in the UK is
      partly attributable to an uncertain clinical environment but the quality of
      judgements is influenced by the how well nurses' confidence and accuracy are
      aligned. OBJECTIVES: To assess UK community nurses' confidence in the accuracy of
      their diagnostic judgements and treatment choices when managing venous leg
      ulceration. DESIGN: Judgement Analysis. SETTING: UK community and primary care
      nursing services. PARTICIPANTS: 18 community non-specialist nurses working in
      district (home) nursing teams and general practitioner services and 18 community
      tissue viability specialist nurses. METHODS: Using judgement analysis methods, 18
      community non-specialist nurses and 18 community tissue viability specialist
      nurses made diagnoses and treatment judgements about compression therapy for 110
      clinical scenarios and indicated their confidence for each judgement. An expert
      panel made consensus judgements for the same scenarios and these judgements were
      used as a standard against which to compare the participants. Confidence analysis
      was used to assess the nurses' confidence about their diagnostic judgements and
      treatment choices. RESULTS: Despite being very experienced, both non-specialist
      nurses' and specialist tissue viability nurses' levels of confidence were not
      well calibrated with their levels of accuracy. CONCLUSION: The results of this
      study are important as errors resulting from both over and under-confidence at
      the diagnostic phase of management may influence treatment choices, and thus
      increase the chances of treatment error.

PMID- 28747259
TI  - Effects of biochar amendment on bacterial and fungal diversity for co-composting
      of gelatin industry sludge mixed with organic fraction of municipal solid waste.
AB  - The aim of the study was to evaluate the bacterial and fungal diversities of
      18contrastivecomposts applied with 17 different sources mad biochars applied
      treatments using 16S rRNA and 18S rDNA technology, while T-1 used as a control.
      The results showed that bacterial species of the phyla Actinobacteria,
      Proteobacteria and Chloroflexi, and fungi of the phylum Ascomycota and
      Basidiomycota were pre-dominant among the all treatments. The bacterial genus
      Subgroup_6_norank, Nocardioides, Pseudonocardia, Sphingomonas, Solirubrobacter
      and RB41_norank are first time identified in composting ecosystem. In addition,
      the fungal genus Ascomycota_unclassified, Aspergillus, Penicillium,
      Pleosporales_unclassified and Herpotrichlellacease_unclassified ubiquitous among
      the all compost. The Shannon and refraction-curve biodiversity indices showed a
      clear heterogeneity among all the treatments, which could be due to isolation of
      new genera in this system. Finally, the principal component analysis of the
      relative number of sequences also confirmed that bacterial and fungal population
      indiscriminate in different sources mad biochar applied treatments.

PMID- 28747260
TI  - Functional connectivity of the left DLPFC to striatum predicts treatment response
      of depression to TMS.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is a non-invasive,
      safe, and efficacious treatment for depression. TMS has been shown to normalize
      abnormal functional connectivity of cortico-cortical circuits in depression and
      baseline functional connectivity of these circuits predicts treatment response.
      Less is known about the relationship between functional connectivity of
      frontostriatal circuits and treatment response. OBJECTIVE/HYPOTHESIS: We
      investigated whether baseline functional connectivity of distinct frontostriatal
      circuits predicted response to TMS. METHODS: Resting-state fMRI (rsfMRI) was
      acquired in 27 currently depressed subjects with treatment resistant depression
      and 27 healthy controls. Depressed subjects were treated with 5 weeks of daily
      TMS over the left dorsolateral prefrontal cortex (DLPFC). The functional
      connectivity between limbic, executive, rostral motor, and caudal motor regions
      of frontal cortex and their corresponding striatal targets were determined at
      baseline using an existing atlas based on diffusion tensor imaging. TMS treatment
      response was measured by percent reduction in the 24-item Hamilton Depression
      Rating Scale (HAMD24). In an exploratory analysis, correlations were determined
      between baseline functional connectivity and TMS treatment response. RESULTS:
      Seven cortical clusters belonging to the executive and rostral motor
      frontostriatal projections had reduced functional connectivity in depression
      compared to healthy controls. No frontostriatal projections showed increased
      functional connectivity in depression (voxel-wise p < 0.01, family-wise alpha <
      0.01). Only baseline functional connectivity between the left DLPFC and the
      striatum predicted TMS response. Higher baseline functional connectivity
      correlated with greater reductions in HAMD24 (Pearson's R = 0.58, p = 0.002).
      CONCLUSION(S): In an exploratory analysis, higher functional connectivity between
      the left DLPFC and striatum predicted better treatment response. Our findings
      suggest that the antidepressant mechanism of action of TMS may require
      connectivity from cortex proximal to the stimulation site to the striatum.

PMID- 28747261
TI  - Enterovirus D68 infection in a cluster of children with acute flaccid myelitis,
      Buenos Aires, Argentina, 2016.
AB  - OBJECTIVE: To report a outbreak of 11 cases of acute asymmetric flaccid
      myelopathy due to spinal motor neuron injury. MATERIAL AND METHODS: Eleven
      children, six male, with a mean age of 3 years presented with acute flaccid
      myelitis. We analyzed clinical features, etiology, neuroradiological images,
      treatment, and outcome. RESULTS: Nine children had bilateral and asymmetric
      flaccid myelitis of the upper limbs, 1 had upper limb monoplegia, and 1 presented
      with hemiparesis. The cranial nerves were involved in 6 patients and 4 required
      mechanical ventilation. In all cases acute flaccid myelitis co-occurred with
      upper airway infection and/or fever. Spinal cord magnetic resonance imaging was
      abnormal in all, showing 2 different patterns: A linear pattern involving the
      anterior horns and another that was more heterogeneous showing spinal cord
      expansion. The lesions were non-enhancing in all. In 5/11 patients involvement of
      the medulla oblongata and pons was also observed. None of the patients presented
      with supratentorial lesions. In 4/11 children, the human enterovirus subtype D68
      (HEV-D68) was identified in the airway and in 1/11 in the cerebrospinal fluid as
      well. In the remaining patients different enterovirus species A, B, and C
      variants were detected, as well as rhinovirus in 1 and influenza in another. Ten
      children received treatment with intravenous immunoglobulin and steroids and 4 of
      these children also underwent plasma exchange. Treatment did not lead to clinical
      improvement. CONCLUSIONS: In a patient with acute flaccid myelitis, HEV-D68
      infection should be ruled out. Cases in which the virus was not detected were
      considered as "false negatives" as samples were collected late in course of the
      disease. The lack of response to anti-inflammatory and immunomodulatory treatment
      suggests a direct viral mechanism. This study is to our knowledge the first on an
      HEV-D68-infection-related cluster in Latin America.

PMID- 28747262
TI  - In reply.

PMID- 28747263
TI  - The validity and reliability of computed tomography orbital volume measurements.
AB  - PURPOSE: Orbital volume calculations allow surgeons to design patient-specific
      implants to correct volume deficits. It is estimated that changes as small as 1
      ml in orbital volume can lead to enophthalmos. Awareness of the limitations of
      orbital volume computed tomography (CT) measurements is critical to differentiate
      between true volume differences and measurement error. The aim of this study is
      to analyze the validity and reliability of CT orbital volume measurements.
      MATERIALS AND METHODS: A total of 12 cadaver orbits were scanned using a standard
      CT maxillofacial protocol. Each orbit was dissected to isolate the extraocular
      muscles, fatty tissue, and globe. The empty bony orbital cavity was then filled
      with sculpting clay. The volumes of the muscle, fat, globe, and clay (i.e., bony
      orbital cavity) were then individually measured via water displacement. The CT
      derived volumes, measured by manual segmentation, were compared to the direct
      measurements to determine validity. RESULTS AND CONCLUSIONS: The difference
      between CT orbital volume measurements and physically measured volumes is not
      negligible. Globe volumes have the highest agreement with 95% of differences
      between -0.5 and 0.5 ml, bony volumes are more likely to be overestimated with
      95% of differences between -1.8 and 2.6 ml, whereas extraocular muscle volumes
      have poor validity and should be interpreted with caution.

PMID- 28747264
TI  - Free-flap surgical correction of facial deformity after anteromedial
      maxillectomy.
AB  - Anteromedial maxillectomy is typically performed in conjunction with low-dose
      radiotherapy and intraarterial chemotherapy. In doing so, the extent of surgical
      defects is reduced. However, nasal deviation and oral incompetence may ensue, due
      to cicatricial contracture of wounds, and may be distressing to these patients.
      Herein, we report a series of eight free perforator flap procedures
      (anterolateral thigh [ALT] flap, 6; thoracodorsal artery perforator [TAP] flap,
      2) used to correct such deformities. The TAP flap was combined with scapular tip
      [ST] osseous flap in patients with added zygomatic prominence defects. Three
      adipocutaneous parts developed from each perforator flap were applied as follows:
      two to reconstruct nasal lining and oral vestibule, and one to augment cheek
      volume. All aesthetic results proved satisfactory, although orbital dystopia and
      contracture of mimic muscles were not resolved completely. These secondary
      interventions are suitable for sequelae of simple anteromedial maxillectomy.
      Immediate reconstruction should be considered if orbital floor and mimic muscles
      are involved.

PMID- 28747265
TI  - Pancreatic adenocarcinoma: effects of neoadjuvant therapy on post-pancreatectomy
      outcomes - an American College of Surgeons National Surgical Quality Improvement
      Program targeted variable review.
AB  - BACKGROUND: As the incidence of pancreatic adenocarcinoma increases, so has the
      utilization of neoadjuvant therapy. The objective of this study was to evaluate
      outcomes in patients undergoing neoadjuvant therapy or surgery first for
      pancreatic adenocarcinoma. METHODS: The ACS-NSQIP 2014-2015 targeted
      pancreatectomy variables were queried for patients with pancreatic adenocarcinoma
      who underwent resection. Outcomes of those receiving neoadjuvant therapy were
      compared to surgery first using a multivariate, logistic regression model.
      RESULTS: 3408 patients underwent pancreatectomy; 2596 proximal pancreatectomies,
      741 distal pancreatectomies, 64 total pancreatectomies and 7 other pancreatic
      procedures were performed. Of the 3408 patients identified, 934 (27.5%) received
      neoadjuvant therapy: 496 chemotherapy alone, 28 radiation alone, and 410 combined
      chemotherapy/radiation therapy. Overall morbidity and mortality were similar
      between patients receiving neoadjuvant therapy versus those who underwent surgery
      first. Neoadjuvant treatment was associated with lower rates of pancreatic
      fistulas (10.2% vs. 13.2%, P = 0.017), but higher intra/postoperative transfusion
      rates (27.4% vs. 20.3%, P < 0.0001). CONCLUSIONS: Neoadjuvant therapy appeared to
      be safe prior to operative intervention as no difference in overall postoperative
      morbidity or mortality rates were identified. There were increased
      intra/postoperative transfusions in the neoadjuvant therapy group, but
      neoadjuvant therapy was associated with lower rates of pancreatic fistulas.

PMID- 28747266
TI  - IgG4, complement, and the mechanisms of blister formation in pemphigus and
      bullous pemphigoid.
AB  - Autoimmune bullous diseases are at the forefront of the research field on
      autoimmune diseases. Pemphigus and pemphigoid were historical entities in the
      world of descriptive dermatology for a long time. Recently, however,
      dermatologists and skin biologists have elegantly explained the novel
      pathomechanism of pemphigus and pemphigoid diseases. IgG4 is the major subclass
      of autoantibodies in autoimmune bullous diseases and is known to have little
      activity to activate complement. It is quite acceptable for pemphigus, because
      acantholysis in pemphigus has been demonstrated to be complement-independent. On
      the other hand, subepidermal blister formation in bullous pemphigoid has been
      believed to be complement-dependent. Therefore, the role of IgG4 autoantibodies
      on blister formation in bullous pemphigoid remains controversial. Here, we
      examine the progress of research on the mechanisms of blister formation in
      autoimmune bullous diseases. We focus on the complement-dependent and independent
      blistering in bullous pemphigoid using comparisons between pemphigus diseases. In
      addition, we review the current understanding of the role of IgG4 antibodies in
      bullous pemphigoid.

PMID- 28747267
TI  - A new femoral fixation device for anterior cruciate ligament reconstruction using
      the outside-in technique and hamstring tendon graft: A comparison between two
      devices in cadaveric human knee models.
AB  - BACKGROUND: A new device (T-anchor) was developed for ACL reconstruction and is
      implanted via the outside-in technique using hamstring grafts. The purpose of
      this study was to compare the T-anchor with the EndoButton Direct. METHODS: This
      study was conducted on 30 cadaveric knees (15 matched pairs). There were two
      groups of 15 each in the T-anchor and EndoButton Direct groups. After the harvest
      of grafts, fixation site profile and graft length were measured by loading the
      grafts onto both devices. They were then tested on a universal testing machine to
      assess elongation after cyclic loading, load to failure, ultimate load, and mode
      of failure. RESULTS: The fixation site profile was lower in the T-anchor group
      than in the EndoButton Direct group (2.3+/-0.4mm vs. 4.7+/-1.0mm, P<0.001). The
      length of the graft-device complex of the T-anchor specimens was longer than that
      of the EndoButton Direct specimens (125.0+/-8.9mm vs. 115.0+/-8.7mm, P<0.001).
      The mean cyclic elongation was lower for the T-anchor group when compared with
      the EndoButton Direct group (2.4+/-0.6mm vs. 3.9+/-2.6mm, P=0.015). There was no
      statistically significant difference in ultimate load and load to failure between
      the T-anchor and EndoButton Direct groups. For mode of failure, the T-anchor
      fared better (P=0.013) with all failures attributed to specimens. CONCLUSIONS: In
      this cadaveric study, the new device, T-anchor, performed better than the
      EndoButton Direct with respect to the above-mentioned study parameters except for
      ultimate load and load to failure.

PMID- 28747268
TI  - Screening of depression in cardiology: A study on 617 cardiovascular patients.
AB  - BACKGROUND: Depression screening in the cardiovascular disease (CVD) care setting
      is under-performed, also because the issue of the optimal screening tools cut-off
      is still open. We analysed which HADS (Hospital Anxiety and Depression Scale)
      total score cut-off value shows the best properties in two groups of 357 Acute
      Coronary Syndrome (ACS) and 260 Chronic Coronary Artery Disease (CAD)
      hospitalized patients. METHODS: A Receiver Operating Characteristics (ROC) curve
      was plotted for both groups using the Montgomery-Asberg Depression Rating Scale
      (MADRS) as the criterion. Accuracy, positive (PPV) and negative (NPV) predictive
      values were computed for different cut-off scores. RESULTS: The ROC curves
      confirmed the excellent/very good accuracy of the HADS in both groups, with an
      area under the curve of 0.911 for the ACS and 0.893 for the CAD patients. The cut
      off of 14 showed the best compromise between high sensitivity and good
      specificity in both groups, with high negative predicted values (95.5% and 92.4%,
      respectively). CONCLUSION: Using a cut-off value of 14, the HADS could be
      considered a good screening tool to identify hospitalized CAD and ACS patients
      requiring a more accurate depression assessment, in order to promptly plan the
      most appropriate treatment strategies and prevent the negative effects of
      depression in CVD patients.

PMID- 28747269
TI  - High-intensity interval training and cardiac autonomic control in individuals
      with metabolic syndrome: A randomised trial.
AB  - BACKGROUND: Insulin resistance has been postulated to play a central role in the
      co-appearance of various cardiovascular disease risk factors constituting the
      metabolic syndrome (MetS). There is evidence that altered cardiac autonomic
      function (CAF) may precede the onset of insulin resistance. Exercise training has
      been shown to improve CAF in different populations, yet little is known regarding
      the exercise dose response for CAF. The aim of this study was to investigate the
      impact of different volumes of high-intensity interval training (HIIT) and
      traditional moderate-intensity continuous training (MICT) on CAF in participants
      with MetS. METHODS: Individuals with MetS (n=56) were randomised into the
      following 16-week training interventions: i) MICT (n=16, 30min at 60-70%HRpeak,
      5*/week); ii) 4HIIT (n=19, 4*4min bouts at 85-95%HRpeak, interspersed with 3min
      of active recovery at 50-70%HRpeak, 3*/week); or iii) 1HIIT (n=21, 1*4min bout at
      85-95%HRpeak, 3*/week). R-R interval recorded for 5min in a supine position at
      pre- and post-intervention was used to derive linear (SDNN, RMSSD, pNN50, LF, HF,
      LF/HF) and non-linear (SD1, SD2, Alpha1, Alpha2, SampEn) heart rate variability
      (HRV) indices as measures of CAF. Group*time interaction effects were examined
      (ANCOVA) and Eta squared (eta2) interaction effect sizes calculated. RESULTS:
      While there were no significant between-group differences in CAF indices, there
      were small-to-medium group*time interaction effects on SDNN [F(2,52)=0.70,
      p=0.50, eta2=0.02], RMSSD [F(2,52)=1.35, p=0.27, eta2=0.03], HF power
      [F(2,52)=1.27, p=0.29, eta2=0.03], SD1 [F(2,52)=0.47, p=0.63, eta2=0.01], and SD2
      [F(2,52)=0.41, p=0.67, eta2=0.01]. The following represent the relative
      percentage increases across these variables for 4HIIT, MICT, and 1HIIT
      respectively (SDNN, +30%, +17%, 9%; RMSSD, +30%, +22%, -2%; HF power, +69%, +18%,
      +7%; SD1, +30%, +22%,-2%; SD2, +22%, +14%, 4%). CONCLUSIONS: There were no
      significant between-group differences for the effects of exercise dose on CAF
      indices, however; high-volume HIIT demonstrated the greatest magnitude of effect
      for improving CAF in individuals with MetS.

PMID- 28747270
TI  - Predictive power of the grace score in population with diabetes.
AB  - INTRODUCTION: Current clinical practice guidelines recommend risk stratification
      in patients with acute coronary syndrome (ACS) upon admission to hospital.
      Diabetes mellitus (DM) is widely recognized as an independent predictor of
      mortality in these patients, although it is not included in the GRACE risk score.
      OBJECTIVES: The objective of this study is to validate the GRACE risk score in a
      contemporary population and particularly in the subgroup of patients with
      diabetes, and to test the effects of including the DM variable in the model.
      MATERIAL AND METHODS: Retrospective cohort study in patients included in the
      ARIAM-SEMICYUC registry, with a diagnosis of ACS and with available in-hospital
      mortality data. We tested the predictive power of the GRACE score, calculating
      the area under the ROC curve. We assessed the calibration of the score and the
      predictive ability based on type of ACS and the presence of DM. Finally, we
      evaluated the effect of including the DM variable in the model by calculating the
      net reclassification improvement. RESULTS: The GRACE score shows good predictive
      power for hospital mortality in the study population, with a moderate degree of
      calibration and no significant differences based on ACS type or the presence of
      DM. Including DM as a variable did not add any predictive value to the GRACE
      model. CONCLUSIONS: The GRACE score has an appropriate predictive power, with
      good calibration and clinical applicability in the subgroup of diabetic patients.

PMID- 28747271
TI  - Diagnostic Accuracy of Split-Bolus Single-Phase Contrast-Enhanced Cone-Beam CT
      for the Detection of Liver Tumors before Transarterial Chemoembolization.
AB  - PURPOSE: To evaluate detectability of hepatocellular carcinoma (HCC) using split
      bolus cone-beam CT in intraindividual comparison between cone-beam CT and
      contrast-enhanced MR imaging. MATERIALS AND METHODS: In a retrospective, single
      center study, 28 patients with 85 HCC tumors were treated with transarterial
      chemoembolization between May 2015 and June 2016. All patients underwent arterial
      and hepatobiliary phase (HBP) MR imaging within 1 month before transarterial
      chemoembolization. Cone-beam CT images were acquired using a split-bolus contrast
      injection with 2 contrast injections and 1 cone-beam CT acquisition. Statistical
      analyses included Friedman 2-way analysis, Kendall coefficient of concordance,
      and Wilcoxon test. Tumor detectability was scored using a 5-point system (1 =
      best; 5 = worst) by 2 independent readers resulting in 170 evaluated tumors.
      Quantitative analysis included signal-to-noise and contrast-to-noise ratio and
      contrast measurements. P values < .05 were considered significant. RESULTS:
      Better tumor detection was provided with split-bolus cone-beam CT (2.91/2.73) and
      HBP MR imaging (2.93/2.21) compared with arterial MR imaging (3.72/3.05; P <
      .001) without statistical difference between cone-beam CT and HBP MR imaging in
      terms of detectability (P = .154) and sensitivity for hypervascularized tumors.
      More tumors were identified on cone-beam CT (n = 121/170) than on arterial MR
      imaging (n = 94/170). Average contrast-to-noise ratio values of arterial and HBP
      MR imaging were higher than for cone-beam CT (7.79, 8.58, 4.43), whereas contrast
      values were higher for cone-beam CT than for MR imaging (0.11, 0.13, 0.97).
      CONCLUSIONS: Split-bolus cone-beam CT showed excellent detectability of HCC.
      Sensitivity is comparable to HBP MR imaging and better than arterial phase MR
      imaging.

PMID- 28747272
TI  - Efficacy and Safety of Radiofrequency Ablation for Focal Hepatic Lesions Adjacent
      to Gallbladder: Reconfiguration of the Ablation Zone through Probe Relocation and
      Ablation Time Reduction.
AB  - PURPOSE: To evaluate the safety and efficacy of radiofrequency (RF) ablation for
      treatment of focal hepatic lesions adjacent to the gallbladder with electrode
      relocation and ablation time reduction. MATERIALS AND METHODS: Thirty-nine
      patients who underwent RF ablation for focal hepatic lesions adjacent to the
      gallbladder (<= 10 mm) were evaluated retrospectively from January 2011 to
      December 2014 (30 men and 9 women; age range, 51-85 y; mean age, 65 y). Of 36
      patients with hepatocellular carcinoma, 3 had a second treatment for recurrence
      (mean tumor size, 15 mm +/- 6). Patients were divided into 2 subgroups based on
      lesion distance from the gallbladder: nonabutting (> 5 mm; n = 19) and abutting
      (<= 5 mm; n = 20). Electrodes were inserted parallel to the gallbladder through
      the center of a tumor in the nonabutting group and through the center of the
      expected ablation zone between a 5-mm safety zone on the liver side and the
      gallbladder in the abutting group. Ablation time was decreased in proportion to
      the transverse diameter of the expected ablation zone. RESULTS: Technical success
      and technical effectiveness rates were 89.7% and 97.4%, respectively, with no
      significant differences between groups (P = 1.00). Local tumor progression was
      observed in 3 patients (1 in the nonabutting group and 2 in the abutting group; P
      = 1.00). There were no major complications. The gallbladder was thickened in 10
      patients, with no significant difference between groups (P = .72). Biloma
      occurred in 1 patient in the nonabutting group. CONCLUSIONS: RF ablation with
      electrode relocation and reduction of ablation time can be a safe and effective
      treatment for focal hepatic lesions adjacent to the gallbladder.

PMID- 28747273
TI  - PrEP on demand or every day?

PMID- 28747275
TI  - Classifying glenohumeral synovitis: a novel intraoperative scoring system.
AB  - BACKGROUND: Synovitis of the shoulder is a common entity that is poorly
      described. This study aims to create a simple and reliable classification system
      for glenohumeral synovitis, which would benefit further research related to
      synovitis and outcomes. METHODS: Twenty 30-second shoulder arthroscopy videos
      were distributed to 19 fellowship-trained orthopedic surgeons. The observers
      responded with their years in practice, fellowship type, whether synovitis
      affects outcomes, and whether synovitis affects plans. The surgeons then rated
      the videos based on the following: color of capsule (pale, pink, or red); villous
      projections (none, few, or extensive); capillaries in capsule (scattered or
      hypertrophied); and axillary recess (normal or contracted). Scores ranging from 0
      to 6 were assigned. The videos were randomized and redistributed at a later date.
      Statistical analysis used an intraclass correlation coefficient with a mixed
      effects model to calculate variability based on observer. RESULTS: Nineteen
      observers completing the survey twice resulted in 760 videos being scored. There
      were 12 shoulder surgeons and 7 sports surgeons. Only 4 surgeons believed that
      synovitis did not affect outcomes, and the remaining 15 believed that it did. The
      intraclass correlation coefficient showed that 68% of the variation in measured
      scores was due to variation among patients and only 4% was due to variation among
      observers. There was no significant variation seen in scores due to surgeon
      experience, surgeon specialty, or first and second viewing. CONCLUSIONS: This
      interclass observer reliability shoulder synovitis study defined a system with
      excellent reliability among a range of surgeons with diverse training and
      experience. In addition, there was excellent reliability for the same surgeon
      between viewings.

PMID- 28747274
TI  - Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure
      prophylaxis for HIV in men who have sex with men: an observational cohort study.
AB  - BACKGROUND: Data for on-demand pre-exposure prophylaxis (PrEP) are scarce. We
      implemented a cohort study to assess its efficacy, safety, and effect on sexual
      behaviour. METHODS: We invited men and transgender women who have sex with men,
      previously enrolled in the randomised placebo-controlled ANRS IPERGAY trial at
      seven sites (six in France and one in Canada), to participate in an open-label
      extension with on-demand tenofovir disoproxil fumarate (300 mg) and emtricitabine
      (200 mg) to be taken before and after sexual intercourse. We assessed the
      incidence of HIV and other sexually transmitted infections (STIs), PrEP
      adherence, safety, and sexual behaviour. Statistical analyses included
      comparisons of proportions and incidence between the randomised phase of the ANRS
      IPERGAY trial and the open-label phase, and all participants were included in
      safety analyses. ANRS IPERGAY is registered with ClinicalTrials.gov, number
      NCT01473472. FINDINGS: Between Nov 4, 2014, and Jan 27, 2015, we enrolled 361
      participants. Median follow-up was 18.4 months (IQR 17.7-19.1). One participant
      who discontinued PrEP acquired HIV infection. HIV incidence was 0.19 per 100
      person-years (95% CI 0.01-1.08), compared with 6.60 per 100 person-years (3.60
      11.05) in the placebo group of the randomised study, indicating a relative
      reduction of 97% (95% CI 81-100) in the incidence of HIV with on-demand PrEP.
      Participants used a median of 18 pills of study drugs per month (IQR 11-25), and
      at the 6 month visit 240 (71%) of 336 participants had tenofovir detected in
      plasma. Drug-related gastrointestinal events were reported in 49 participants
      (14%) but were self-limited. Only four participants (1%) discontinued PrEP, three
      because of an increase in plasma creatinine. The proportion of participants
      reporting condomless sex at their last receptive anal intercourse significantly
      increased from 77% (136 of 176 participants) at baseline to 86% (66 of 77
      participants) at 18 months' follow-up (p for trend=0.0004). The incidence of a
      first bacterial STI during this open-label phase did not change significantly
      compared with the randomised phase (59.0 vs 49.1 per 100 person-years,
      respectively; p=0.11). INTERPRETATION: On-demand oral PrEP is highly effective at
      preventing HIV infection among high-risk men who have sex with men and therefore
      represents an alternative to daily PrEP, expanding choices for HIV prevention.
      High rates of STIs resulting from low condom use did not undermine PrEP efficacy,
      but warrant frequent testing. FUNDING: ANRS (France Recherche Nord and Sud Sida
      HIV Hepatites), the Canadian HIV Trials Network, Fonds Pierre Berge-Sidaction,
      Gilead Sciences, and the Bill & Melinda Gates Foundation.

PMID- 28747276
TI  - Tobacco use predicts a more difficult episode of care after anatomic total
      shoulder arthroplasty.
AB  - BACKGROUND: In the current health care environment, it is becoming increasingly
      important to recognize risks factors that may affect a patient's postoperative
      outcome. To determine the potential impact of tobacco as a risk factor, we
      evaluated postoperative pain, narcotic use, length of stay, reoperations, and
      complications in the global 90-day episode of care for patients undergoing
      anatomic total shoulder arthroplasty (TSA) who were current tobacco users, former
      users, or nonusers. METHODS: Database search identified 163 patients with primary
      anatomic TSA done for glenohumeral arthritis; these were divided into 3 groups:
      current tobacco users (28), nonusers (88), and former users (47). All surgeries
      were done with the same technique and implants. RESULTS: Patients in the current
      tobacco use group had significantly higher visual analog scale scores
      preoperatively and at 12 weeks postoperatively than nonusers and former users.
      Mean improvement in visual analog scale scores was significantly less in current
      tobacco users. Cumulative oral morphine equivalent use at 12 weeks was
      significantly higher in current tobacco users than in nonusers and former users.
      The average oral morphine equivalent per day was also significantly higher in the
      current tobacco users than in nonusers and former users. There were no
      significant differences in length of stay or complications. CONCLUSIONS: Although
      length of stay, complication rates, hospital readmissions, and reoperation rates
      were not significantly different, tobacco users reported increased postoperative
      pain and narcotic use in the global period after TSA. Former tobacco users were
      found to have a postoperative course similar to that of nonusers, suggesting that
      discontinuation of tobacco use can improve a patient's episode of care
      performance after TSA.

PMID- 28747277
TI  - Glenosphere size in reverse shoulder arthroplasty: is larger better for external
      rotation and abduction strength?
AB  - BACKGROUND: The role of glenosphere size in reverse shoulder arthroplasty (RSA)
      may be important in prosthetic stability, joint kinematics, rotator cuff tension
      and excursion, scapular impingement, humeral lateralization, deltoid wrap, and
      the occurrence of "notching." This study compared short- and midterm clinical and
      radiographic outcomes for 2 different glenosphere sizes of a single RSA type with
      respect to implant positioning, glenoid size, and morphology. METHODS: This
      retrospective analysis included 68 RSA procedures that were prospectively
      documented in a local register during a 5-year postoperative period. Two
      glenosphere diameter sizes of 36 mm (n = 33) and 44 mm (n = 35) were used.
      Standard radiographs were made preoperatively (ie, baseline) and at 6, 12, 24,
      and 60 months after surgery. Range of motion, strength, the Constant-Murley
      score, and the Shoulder Pain and Disability Index were also assessed at all
      follow-up visits. The effect of glenosphere size on measured outcomes was
      adjusted for baseline values, patient gender, and humeral head diameter. RESULTS:
      No significant differences were found in the functional scores between treatment
      groups at all follow-up assessments. At the 12-month follow-up, patients with a
      44-mm glenosphere had greater external rotation in adduction (mean difference, 12
      degrees ; P = .001) and abduction strength (mean difference, 1.4 kg; P = .026)
      compared with those with the smaller implant. These differences remained at 60
      months. Scapular notching was observed in 38% of all patients, without any
      relevant difference between the groups. CONCLUSION: An increase in glenosphere
      diameter leads to a clinically moderate but significant increase in external
      rotation in adduction and abduction strength at midterm follow-up.

PMID- 28747278
TI  - Essential tremor then and now: How views of the most common tremor diathesis have
      changed over time.
AB  - BACKGROUND: Essential tremor (ET) is the most prevalent tremor diathesis. In this
      "then" and "now" piece, I detail how views of this disorder have changed over
      time. METHODS: A PubMed search was conducted on June 15, 2017. The term
      "essential tremor" was crossed in sequential order with 14 s search terms (e.g.,
      genetics, clinical). RESULTS: The traditional view of ET was that it was
      monosymptomatic. An emerging view of ET is as a more clinically-complex entity
      with a range of possible motor and non-motor features. Traditionally, ET was
      viewed as autosomal dominant with complete penetrance by age 65. Current thinking
      is that, in addition to monogenic forms of ET, the disease is likely to be
      complex, with incomplete penetrance into advanced age. While non-genetic factors
      were traditionally presumed to exist, epidemiological studies have explored
      several potential environmental toxicants. The traditional olivary model of ET
      posited the existence of a central oscillator; an alternative is the cerebellar
      degenerative model, which is now under consideration. CONCLUSIONS: For ET, there
      is clearly a "then" and "now" when one assesses changes in our understanding of
      the disease with time. Indeed, concepts relating to the clinical features,
      disease etiology and pathogenesis have all changed substantially.

PMID- 28747279
TI  - Portable objective assessment of upper extremity motor function in Parkinson's
      disease.
AB  - INTRODUCTION: Objective, portable measures of motor function for out-of-office
      assessments are needed in Parkinson's Disease (PD). This study had 3 objectives.
      First, to examine change in objective motor measurements in PD (as assessed with
      the Objective PD Measurement (OPDM) system). Second, to correlate objective
      measures with clinical features and putative PD cerebrospinal fluid (CSF) and
      dopaminergic imaging biomarkers. Third, to assess participant compliance with and
      perceptions of serial in-home motor assessments. METHODS: De novo PD subjects
      participating in this pilot study of the Parkinson Progression Markers Initiative
      (PPMI) completed OPDM assessments at home weekly for 3 months and in the clinic
      at baseline and 3-, 6-, and 12-months. Tasks included (i)digitography (ii)a
      repetitive hand tapping task and (iii)timed pegboard task. A global objective
      motor score (OMS) was derived from the latter three. MDS-UPDRS-III score was
      obtained at each time point, and CSF and dopamine transporter (DAT) SPECT at
      baseline. RESULTS: 27 participants, mean age 62.6 years, 19 male were included. A
      mean of 10.5 in-home assessments were completed. There was no significant change
      in in-home OMS over 12 weeks (p = 0.48). There was strong correlation between
      mean baseline OMS and MDS-UPDRS-III scores (spearman's rho = 0.60, p=<0.0001).
      Baseline OMS predicted 6-month MDS-UPDRS-III (beta = 0.80, p = 0.0002) but not
      change in MDS-UPDRS-III score, DAT SPECT, or putative CSF biomarkers.
      CONCLUSIONS: This study suggests that administration of in-home motor tasks as
      part of a large multi-center study is feasible and scores derived from these
      assessments may serve as surrogates of in-person clinician-assessed motor score.

PMID- 28747280
TI  - The evolving definition of essential tremor: What are we dealing with?
AB  - BACKGROUND: Although essential tremor (ET) is commonly encountered in clinical
      practice, historically, there has been considerable disagreement as how to best
      define it, and now with a growing sense of its clinical complexity, how to best
      encapsulate it. Here, I draw attention to five issues of current uncertainty.
      METHODS: A PubMed search conducted on June 19, 2017 crossed "essential tremor"
      with 9 second search terms (e.g., definition, diagnosis). RESULTS: There are
      several major issues of clinical and diagnostic uncertainty. Underlying each
      issue is a larger question about the nature of the underlying pathophysiology of
      ET. Does age of onset of ET matter? How much dystonia is acceptable in ET? How
      much in the way of "cerebellar signs" are acceptable? Are non-motor features due
      to the underlying disease or merely secondary to the clinical features? Is ET a
      single disease entity or something else? CONCLUSIONS: We are learning more about
      ET and, as a by-product of these efforts, are struggling with its definition.
      Further understanding the nature of the underlying disease pathogenesis as well
      as the role the cerebellum and cerebellar relays play in this process will likely
      provide important clues to enable us to bring order to areas of uncertainty.

PMID- 28747281
TI  - Transcutaneous Electrical Nerve Stimulation in Children with Monosymptomatic
      Nocturnal Enuresis: A Randomized, Double-Blind, Placebo Controlled Study.
AB  - PURPOSE: In a third of all children with monosymptomatic nocturnal enuresis their
      condition is refractory to first line treatments. Transcutaneous electrical nerve
      stimulation has been documented to be efficacious in children with daytime
      incontinence. We investigated the effect of transcutaneous electrical nerve
      stimulation in children with monosymptomatic nocturnal enuresis without nocturnal
      polyuria. MATERIALS AND METHODS: Children with monosymptomatic nocturnal enuresis
      (3 or more wet nights per week) and no nocturnal polyuria were randomized to
      treatment with active or sham transcutaneous electrical nerve stimulation
      involving 1-hour sessions twice daily for 10 weeks in a double-blind design.
      RESULTS: Of the 52 children with monosymptomatic nocturnal enuresis included in
      the study 47 completed treatment (mean age 9.5 +/- 2.1 years, 38 males). None of
      the children experienced a full response with complete remission of enuresis.
      Treatment with transcutaneous electrical nerve stimulation did not lead to
      significant changes in number of wet nights, nocturnal urine production on wet or
      dry nights, maximum voided volume with and without first morning voided volume,
      or voiding frequency when comparing parameters before and after treatment.
      CONCLUSIONS: The present study demonstrates no anti-enuretic effect of
      transcutaneous electrical nerve stimulation in children with monosymptomatic
      nocturnal enuresis without nocturnal polyuria. Nocturnal urine production and
      bladder capacity remained unchanged during and after treatment with
      transcutaneous electrical nerve stimulation.

PMID- 28747282
TI  - Editorial Comment.

PMID- 28747283
TI  - A case of lamellar ichthyosis due to a novel TGM1 mutation associated with
      Parkinson's disease.

PMID- 28747284
TI  - Comorbid autoimmune diseases in patients with pemphigus: a nationwide case
      control study in Taiwan.
AB  - Previous studies have proposed the association between pemphigus and several
      autoimmune diseases, but no large-scale study has been reported. To delineate the
      association between pemphigus and autoimmune diseases including psoriasis. A
      total of 1,998 patients with pemphigus and 7,992 control subjects were enrolled
      from the National Health Insurance Research Database in Taiwan from 1997 to 2010.
      The odds of comorbidities between these two groups were analysed by multivariate
      logistic regression. Compared with control subjects, patients with pemphigus were
      much more likely to have Sjogren's syndrome (odds ratio [OR]: 15.0; 95%
      confidence interval [CI]: 3.16-71.5), psoriasis (OR: 7.18; 95% CI: 5.55-9.29),
      systemic lupus erythematosus (OR: 4.46; 95% CI: 1.88-10.6), and alopecia areata
      (OR: 2.68; 95% CI: 1.26-5.67). According to gender-stratified analyses, however,
      the association between pemphigus and Sjogren's syndrome or alopecia areata was
      found to be significant only in the female patients. We confirm the association
      between pemphigus and some autoimmune diseases, including Sjogren's syndrome,
      systemic lupus erythematosus, and alopecia areata. In addition, we present the
      novel finding that patients with pemphigus have an increased risk of psoriasis.

PMID- 28747285
TI  - Awareness and screening attitudes of Portuguese dermatologists on cardiovascular
      risk factors in psoriatic patients.

PMID- 28747286
TI  - Coexistence of EZH2, NOTCH1, IL7R, and PHF6 Mutations in Adult T-cell Acute
      Lymphoblastic Leukemia.

PMID- 28747287
TI  - Three Novel Calreticulin Mutations in Two Turkish Patients.

PMID- 28747288
TI  - Nuclear Projections in Neutrophils for Supporting the Diagnosis of Trisomy 13.

PMID- 28747290
TI  - Acquired Leukocyte Inclusion Bodies Resembling Dohle Bodies During Acute
      Cholangitis.

PMID- 28747291
TI  - Dental Blogs, Podcasts, and Associated Social Media: Descriptive Mapping and
      Analysis.
AB  - BACKGROUND: Studies of social media in both medicine and dentistry have largely
      focused on the value of social media for marketing to and communicating with
      patients and for clinical education. There is limited evidence of how dental
      clinicians contribute to and use social media to disseminate and access
      information relevant to clinical care. OBJECTIVE: The purpose of this study was
      to inventory and assess the entry, growth, sources, and content of clinically
      relevant social media in dentistry. METHODS: We developed an inventory of blogs,
      podcasts, videos, and associated social media disseminating clinical information
      to dentists. We assessed hosts' media activity in terms of their combinations of
      modalities, entry and exit dates, frequency of posting, types of content posted,
      and size of audience. RESULTS: Our study showed that clinically relevant
      information is posted by dentists and hygienists on social media. Clinically
      relevant information was provided in 89 blogs and podcasts, and topic analysis
      showed motives for blogging by host type: 55% (49 hosts) were practicing dentists
      or hygienists, followed by consultants (27 hosts, 30%), media including
      publishers and discussion board hosts (8 hosts, 9%), and professional
      organizations and corporations. CONCLUSIONS: We demonstrated the participation of
      and potential for practicing dentists and hygienists to use social media to share
      clinical and other information with practicing colleagues. There is a clear
      audience for these social media sites, suggesting a changing mode of information
      diffusion in dentistry. This study was a first effort to fill the gap in
      understanding the nature and potential role of social media in clinical
      dentistry.

PMID- 28747292
TI  - Do Physicians Respond to Web-Based Patient Ratings? An Analysis of Physicians'
      Responses to More Than One Million Web-Based Ratings Over a Six-Year Period.
AB  - BACKGROUND: Physician-rating websites (PRWs) may lead to quality improvements in
      case they enable and establish a peer-to-peer communication between patients and
      physicians. Yet, we know little about whether and how physicians respond on the
      Web to patient ratings. OBJECTIVE: The objective of this study was to describe
      trends in physicians' Web-based responses to patient ratings over time, to
      identify what physician characteristics influence Web-based responses, and to
      examine the topics physicians are likely to respond to. METHODS: We analyzed
      physician responses to more than 1 million patient ratings displayed on the
      German PRW, jameda, from 2010 to 2015. Quantitative analysis contained chi-square
      analyses and the Mann-Whitney U test. Quantitative content techniques were
      applied to determine the topics physicians respond to based on a randomly
      selected sample of 600 Web-based ratings and corresponding physician responses.
      RESULTS: Overall, physicians responded to 1.58% (16,640/1,052,347) of all Web
      based ratings, with an increasing trend over time from 0.70% (157/22,355) in 2010
      to 1.88% (6377/339,919) in 2015. Web-based ratings that were responded to had
      significantly worse rating results than ratings that were not responded to (2.15
      vs 1.74, P<.001). Physicians who respond on the Web to patient ratings differ
      significantly from nonresponders regarding several characteristics such as gender
      and patient recommendation results (P<.001 each). Regarding scaled-survey rating
      elements, physicians were most likely to respond to the waiting time within the
      practice (19.4%, 99/509) and the time spent with the patient (18.3%, 110/600).
      Almost one-third of topics in narrative comments were answered by the physicians
      (30.66%, 382/1246). CONCLUSIONS: So far, only a minority of physicians have taken
      the chance to respond on the Web to patient ratings. This is likely because of
      (1) the low awareness of PRWs among physicians, (2) the fact that only a few PRWs
      enable physicians to respond on the Web to patient ratings, and (3) the lack of
      an active moderator to establish peer-to-peer communication. PRW providers should
      foster more frequent communication between the patient and the physician and
      encourage physicians to respond on the Web to patient ratings. Further research
      is needed to learn more about the motivation of physicians to respond or not
      respond to Web-based patient ratings.

PMID- 28747293
TI  - Improving Employee Well-Being and Effectiveness: Systematic Review and Meta
      Analysis of Web-Based Psychological Interventions Delivered in the Workplace.
AB  - BACKGROUND: Stress, depression, and anxiety among working populations can result
      in reduced work performance and increased absenteeism. Although there is evidence
      that these common mental health problems are preventable and treatable in the
      workplace, uptake of psychological treatments among the working population is
      low. One way to address this may be the delivery of occupational digital mental
      health interventions. While there is convincing evidence for delivering digital
      psychological interventions within a health and community context, there is no
      systematic review or meta-analysis of these interventions in an occupational
      setting. OBJECTIVE: The aim of this study was to identify the effectiveness of
      occupational digital mental health interventions in enhancing employee
      psychological well-being and increasing work effectiveness and to identify
      intervention features associated with the highest rates of engagement and
      adherence. METHODS: A systematic review of the literature was conducted using
      Cochrane guidelines. Papers published from January 2000 to May 2016 were searched
      in the PsychINFO, MEDLINE, PubMed, Science Direct, and the Cochrane databases, as
      well as the databases of the researchers and relevant websites. Unpublished data
      was sought using the Conference Proceedings Citation Index and the Clinical
      Trials and International Standard Randomized Controlled Trial Number (ISRCTN)
      research registers. A meta-analysis was conducted by applying a random-effects
      model to assess the pooled effect size for psychological well-being and the work
      effectiveness outcomes. A positive deviance approach was used to identify those
      intervention features associated with the highest rates of engagement and
      adherence. RESULTS: In total, 21 randomized controlled trials (RCTs) met the
      search criteria. Occupational digital mental health interventions had a
      statistically significant effect post intervention on both psychological well
      being (g=0.37, 95% CI 0.23-0.50) and work effectiveness (g=0.25, 95% CI 0.09
      0.41) compared with the control condition. No statistically significant
      differences were found on either outcome between studies using cognitive
      behavioral therapy (CBT) approaches (as defined by the authors) compared with
      other psychological approaches, offering guidance compared with self-guidance, or
      recruiting from a targeted workplace population compared with a universal
      workplace population. In-depth analysis of the interventions identified by the
      positive deviance approach suggests that interventions that offer guidance are
      delivered over a shorter time frame (6 to 7 weeks), utilize secondary modalities
      for delivering the interventions and engaging users (ie, emails and text messages
      [short message service, SMS]), and use elements of persuasive technology (ie,
      self-monitoring and tailoring), which may achieve greater engagement and
      adherence. CONCLUSIONS: This review provides evidence that occupational digital
      mental health interventions can improve workers' psychological well-being and
      increase work effectiveness. It identifies intervention characteristics that may
      increase engagement. Recommendations are made for future research, practice, and
      intervention development.

PMID- 28747294
TI  - Patients' Perspective on Participation in Care With or Without the Support of a
      Smartphone App During Radiotherapy for Prostate Cancer: Qualitative Study.
AB  - BACKGROUND: Patients with prostate cancer are often cared for as outpatients
      during radiotherapy, which can be an aggravating circumstance for patient
      participation. There is a need to evaluate whether an interactive smartphone app
      could enable participation in care, specifically during treatment for prostate
      cancer. The interactive app (Interaktor) used in this study is developed in
      codesign with patients and health care professionals; it includes daily reports
      of symptoms, a risk assessment model, evidence-based self-care advice, along with
      the provision of immediate access to clinicians. OBJECTIVE: The aim of this study
      was to explore how patients with prostate cancer perceived their participation
      with or without the support of the smartphone app during radiotherapy. METHODS: A
      total of 28 prostate cancer patients receiving adjuvant radiotherapy were
      interviewed about their perceived participation in their own care. All the
      patients interviewed in this study participated in an intervention study where
      the control group received standard care that comprised having access to a
      contact nurse to turn to with any concerns during their treatment. In addition to
      standard care, the patients in the intervention group received the app downloaded
      in a smartphone. The patients' age ranged between 57 and 77 years; 17 patients
      used the smartphone app. The interviews were analyzed with directed qualitative
      content analysis. RESULTS: The four dimensions of patient participation, which
      include mutual participation, fight for participation, requirement for
      participation, and participation in getting basic needs satisfied, were confirmed
      as valid perspectives in the interviews with the patients with prostate cancer,
      irrespective of whether they used the smartphone app. However, the patients who
      had used the smartphone app described it as a facilitating factor, especially for
      mutual participation. CONCLUSIONS: Using innovative ways to communicate with
      patients, such as an interactive app for symptom management with contact with
      health care in real time, can successfully help achieve increased patient
      participation in care.

PMID- 28747295
TI  - MotivATE: A Pretreatment Web-Based Program to Improve Attendance at UK Outpatient
      Services Among Adults With Eating Disorders.
AB  - BACKGROUND: In the UK, eating disorders affect upward of 725,000 people per year,
      and early assessment and treatment are important for patient outcomes. Around a
      third of adult outpatients in the UK who are referred to specialist eating
      disorder services do not attend, which could be related to patient factors
      related to ambivalence, fear, and a lack of confidence about change. This lack of
      engagement has a negative impact on the quality of life of patients and has
      implications for service costs. OBJECTIVE: To describe the development of a Web
      based program ("MotivATE") designed for delivery at the point of referral to an
      eating disorder service, with the aim of increasing service attendance. METHODS:
      We used intervention mapping and a person-based approach to design the MotivATE
      program and conducted a needs assessment to determine the current impact of
      service nonattendance on patients (via a review of the qualitative evidence) and
      services (through a service provision survey to understand current issues in UK
      services). Following the needs assessment, we followed the five steps of program
      development outlined by Bartholomew et al (1998): (1) creating a matrix of
      proximal program objectives; (2) selecting theory-based intervention methods and
      strategies; (3) designing and organizing the program; (4) specifying adoption and
      implementation plans; and (5) generating program evaluation plans. RESULTS: The
      needs assessment identified current nonattendance rates of 10%-32%. We defined
      the objective of MotivATE as increasing attendance rates at an eating disorder
      service and considered four key determinants of poor attendance: patient
      ambivalence about change, low patient self-efficacy, recognition of the need to
      change, and expectations about assessment. We chose aspects of motivational
      interviewing, self-determination theory, and the use of patient stories as the
      most appropriate ways to enable change. Think-aloud piloting with people with
      lived experience of an eating disorder resulted in positive feedback on the
      MotivATE program. Participants related well to the stories used. Nonetheless,
      because of feedback, we further modified the program in line with patients' stage
      of change and addressed issues with the language used. A consultation with
      service staff meant that we could make clear implementation plans. Finally, a
      randomized controlled trial is currently underway to evaluate the MotivATE
      program. CONCLUSIONS: Using intervention mapping, we have developed a novel
      pretreatment Web-based program that is acceptable to people with eating
      disorders. To our knowledge, this is the first such program. The model of
      development described here could be a useful template for designing further
      programs for other difficult-to-engage populations.

PMID- 28747296
TI  - Tamper-Resistant Mobile Health Using Blockchain Technology.
AB  - BACKGROUND: Digital health technologies, including telemedicine, mobile health
      (mHealth), and remote monitoring, are playing a greater role in medical practice.
      Safe and accurate management of medical information leads to the advancement of
      digital health, which in turn results in a number of beneficial effects.
      Furthermore, mHealth can help lower costs by facilitating the delivery of care
      and connecting people to their health care providers. Mobile apps help empower
      patients and health care providers to proactively address medical conditions
      through near real-time monitoring and treatment, regardless of the location of
      the patient or the health care provider. Additionally, mHealth data are stored in
      servers, and consequently, data management that prevents all forms of
      manipulation is crucial for both medical practice and clinical trials. OBJECTIVE:
      The aim of this study was to develop and evaluate a tamper-resistant mHealth
      system using blockchain technology, which enables trusted and auditable computing
      using a decentralized network. METHODS: We developed an mHealth system for
      cognitive behavioral therapy for insomnia using a smartphone app. The volunteer
      data collected with the app were stored in JavaScript Object Notation format and
      sent to the blockchain network. Thereafter, we evaluated the tamper resistance of
      the data against the inconsistencies caused by artificial faults. RESULTS:
      Electronic medical records collected using smartphones were successfully sent to
      a private Hyperledger Fabric blockchain network. We verified the data update
      process under conditions where all the validating peers were running normally.
      The mHealth data were successfully updated under network faults. We further
      ensured that any electronic health record registered to the blockchain network
      was resistant to tampering and revision. The mHealth data update was compatible
      with tamper resistance in the blockchain network. CONCLUSIONS: Blockchain serves
      as a tamperproof system for mHealth. Combining mHealth with blockchain technology
      may provide a novel solution that enables both accessibility and data
      transparency without a third party such as a contract research organization.

PMID- 28747297
TI  - Photoaging Mobile Apps as a Novel Opportunity for Melanoma Prevention: Pilot
      Study.
AB  - BACKGROUND: Around 90% of melanomas are caused by ultraviolet (UV) exposure and
      are therefore eminently preventable. Unhealthy tanning behavior is mostly
      initiated in early adolescence, often with the belief that it increases
      attractiveness; the problems related to skin atrophy and malignant melanoma are
      too far in the future to fathom. Photoaging desktop programs, in which an image
      is altered to predict future appearance, have been successful in positively
      influencing behavior in adiposity or tobacco prevention settings. OBJECTIVE: To
      develop and test a photoaging app designed for melanoma prevention. METHODS: We
      harnessed the widespread availability of mobile phones and adolescents' interest
      in appearance to develop a free mobile app called Sunface. This app has the user
      take a self-portrait (ie, a selfie), and then photoages the image based on
      Fitzpatrick skin type and individual UV protection behavior. Afterward, the app
      explains the visual results and aims at increasing self-competence on skin cancer
      prevention by providing guideline recommendations on sun protection and the ABCDE
      rule for melanoma self-detection. The underlying aging algorithms are based on
      publications showing UV-induced skin damage by outdoor as well as indoor tanning.
      To get a first impression on how well the app would be received in a young target
      group, we included a total sample of 25 students in our cross-sectional pilot
      study with a median age of 22 (range 19-25) years of both sexes (11/25, 44%
      female; 14/25, 56% male) attending the University of Essen in Germany. RESULTS:
      The majority of enrolled students stated that they would download the app (22/25,
      88%), that the intervention had the potential to motivate them to use sun
      protection (23/25, 92%) and that they thought such an app could change their
      perceptions that tanning makes you attractive (19/25, 76%). Only a minority of
      students disagreed or fully disagreed that they would download such an app (2/25,
      8%) or that such an app could change their perceptions on tanning and
      attractiveness (4/25, 16%). CONCLUSIONS: Based on previous studies and the
      initial study results presented here, it is reasonable to speculate that the app
      may induce behavioral change in the target population. Further work is required
      to implement and examine the effectiveness of app-based photoaging interventions
      within risk groups from various cultural backgrounds.

PMID- 28747298
TI  - Estimating One-Year Risk of Incident Chronic Kidney Disease: Retrospective
      Development and Validation Study Using Electronic Medical Record Data From the
      State of Maine.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a major public health concern in the
      United States with high prevalence, growing incidence, and serious adverse
      outcomes. OBJECTIVE: We aimed to develop and validate a model to identify
      patients at risk of receiving a new diagnosis of CKD (incident CKD) during the
      next 1 year in a general population. METHODS: The study population consisted of
      patients who had visited any care facility in the Maine Health Information
      Exchange network any time between January 1, 2013, and December 31, 2015, and had
      no history of CKD diagnosis. Two retrospective cohorts of electronic medical
      records (EMRs) were constructed for model derivation (N=1,310,363) and validation
      (N=1,430,772). The model was derived using a gradient tree-based boost algorithm
      to assign a score to each individual that measured the probability of receiving a
      new diagnosis of CKD from January 1, 2014, to December 31, 2014, based on the
      preceding 1-year clinical profile. A feature selection process was conducted to
      reduce the dimension of the data from 14,680 EMR features to 146 as predictors in
      the final model. Relative risk was calculated by the model to gauge the risk
      ratio of the individual to population mean of receiving a CKD diagnosis in next 1
      year. The model was tested on the validation cohort to predict risk of CKD
      diagnosis in the period from January 1, 2015, to December 31, 2015, using the
      preceding 1-year clinical profile. RESULTS: The final model had a c-statistic of
      0.871 in the validation cohort. It stratified patients into low-risk (score 0
      0.005), intermediate-risk (score 0.005-0.05), and high-risk (score >= 0.05)
      levels. The incidence of CKD in the high-risk patient group was 7.94%, 13.7 times
      higher than the incidence in the overall cohort (0.58%). Survival analysis showed
      that patients in the 3 risk categories had significantly different CKD outcomes
      as a function of time (P<.001), indicating an effective classification of
      patients by the model. CONCLUSIONS: We developed and validated a model that is
      able to identify patients at high risk of having CKD in the next 1 year by
      statistically learning from the EMR-based clinical history in the preceding 1
      year. Identification of these patients indicates care opportunities such as
      monitoring and adopting intervention plans that may benefit the quality of care
      and outcomes in the long term.

PMID- 28747299
TI  - Patients cry "whitewash" as NHS refuses to halt use of mesh implants.

PMID- 28747300
TI  - Rise in e-cigarette use linked to increase in smoking cessation rates.

PMID- 28747301
TI  - Pharmaceutical companies' policies on access to trial data, results, and methods:
      audit study.
AB  - Objectives To identify the policies of major pharmaceutical companies on
      transparency of trials, to extract structured data detailing each companies'
      commitments, and to assess concordance with ethical and professional
      guidance.Design Structured audit.Setting Pharmaceutical companies,
      worldwide.Participants 42 pharmaceutical companies.Main outcome measures
      Companies' commitments on sharing summary results, clinical study reports (CSRs),
      individual patient data (IPD), and trial registration, for prospective and
      retrospective trials.Results Policies were highly variable. Of 23 companies
      eligible from the top 25 companies by revenue, 21 (91%) committed to register all
      trials and 22 (96%) committed to share summary results; however, policies
      commonly lacked timelines for disclosure, and trials on unlicensed medicines and
      off-label uses were only included in six (26%). 17 companies (74%) committed to
      share the summary results of past trials. The median start date for this
      commitment was 2005. 22 companies (96%) had a policy on sharing CSRs, mostly on
      request: two committed to share only synopses and only two policies included
      unlicensed treatments. 22 companies (96%) had a policy to share IPD; 14 included
      phase IV trials (one included trials on unlicensed medicines and off-label uses).
      Policies in the exploratory group of smaller companies made fewer transparency
      commitments. Two companies fell short of industry body commitments on
      registration, three on summary results. Examples of contradictory and ambiguous
      language were documented and summarised by theme. 23/42 companies (55%) responded
      to feedback; 7/1806 scored policy elements were revised in light of feedback from
      companies (0.4%). Several companies committed to changing policy; some made
      changes immediately.Conclusions The commitments made by companies to transparency
      of trials were highly variable. Other than journal submission for all trials
      within 12 months, all elements of best practice were met by at least one company,
      showing that these commitments are realistic targets.

PMID- 28747303
TI  - 60 seconds on . . . Black Wednesday.

PMID- 28747305
TI  - Why we must stay in the European Atomic Energy Community.

PMID- 28747304
TI  - Investigating the impact of the English health inequalities strategy: time trend
      analysis.
AB  - Objective To investigate whether the English health inequalities strategy was
      associated with a decline in geographical health inequalities, compared with
      trends before and after the strategy.Design Time trend analysis.Setting Two
      groups of lower tier local authorities in England. The most deprived, bottom
      fifth and the rest of England.Intervention The English health inequalities
      strategy-a cross government strategy implemented between 1997 and 2010 to reduce
      health inequalities in England. Trends in geographical health inequalities were
      assessed before (1983-2003), during (2004-12), and after (2013-15) the strategy
      using segmented linear regression.Main outcome measure Geographical health
      inequalities measured as the relative and absolute differences in male and female
      life expectancy at birth between the most deprived local authorities in England
      and the rest of the country.Results Before the strategy the gap in male and
      female life expectancy between the most deprived local authorities in England and
      the rest of the country increased at a rate of 0.57 months each year (95%
      confidence interval 0.40 to 0.74 months) and 0.30 months each year (0.12 to 0.48
      months). During the strategy period this trend reversed and the gap in life
      expectancy for men reduced by 0.91 months each year (0.54 to 1.27 months) and for
      women by 0.50 months each year (0.15 to 0.86 months). Since the end of the
      strategy period the inequality gap has increased again at a rate of 0.68 months
      each year (-0.20 to 1.56 months) for men and 0.31 months each year (-0.26 to
      0.88) for women. By 2012 the gap in male life expectancy was 1.2 years smaller
      (95% confidence interval 0.8 to 1.5 years smaller) and the gap in female life
      expectancy was 0.6 years smaller (0.3 to 1.0 years smaller) than it would have
      been if the trends in inequalities before the strategy had continued.Conclusion
      The English health inequalities strategy was associated with a decline in
      geographical inequalities in life expectancy, reversing a previously increasing
      trend. Since the strategy ended, inequalities have started to increase again. The
      strategy may have reduced geographical health inequalities in life expectancy,
      and future approaches should learn from this experience. The concerns are that
      current policies are reversing the achievements of the strategy.

PMID- 28747306
TI  - How I treat myeloma with new agents.
AB  - At present, multiple classes of agents with distinct mechanisms of action are
      available for the treatment of patients with multiple myeloma (MM), including
      alkylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors
      (PIs), histone deacetylase inhibitors (DACIs), and monoclonal antibodies (mAbs).
      Over the last 5 years, several new agents, such as the third-generation IMiD
      pomalidomide, the second-generation PIs carfilzomib and ixazomib, the DACI
      panobinostat, and 2 mAbs, elotuzumab and daratumumab, have been approved,
      incorporated into clinical guidelines, and have transformed our approach to the
      treatment of patients. These agents may be part of doublet or triplet
      combinations, or incorporated into intensive strategies with autologous stem cell
      transplantation. In this review, I discuss the different treatment options
      available today for the treatment of MM in frontline and relapse settings.

PMID- 28747308
TI  - Pali Hungin: Racing beyond the boundary.

PMID- 28747307
TI  - Humanitarian leaders call for "redoubling" of aid for crisis engulfing Yemen.

PMID- 28747309
TI  - Five minutes with . . . Paula Bolton-Maggs.

PMID- 28747310
TI  - Advertisements for medical vacancies increase by 8% in a year.

PMID- 28747311
TI  - An N-terminal Pfs230 domain produced in baculovirus as a biological active
      transmission-blocking vaccine candidate.
AB  - Transmission-blocking vaccines have the potential to accelerate malaria parasite
      elimination by inducing antibodies that block parasite transmission from humans
      to mosquitoes. Pfs230, a gametocyte surface protein involved in gamete function,
      has long been a promising candidate. Due to the large size (3,135 amino acids),
      complex domains, and repeating six-cysteine (6-Cys) motifs with a multitude of
      disulfide bonds, the feasibility of expression of a full-length protein has been
      difficult. A priority focus, therefore, has been on the generation of single
      domains, including N-terminal fragments. Here we utilized a heterologous
      expression system, baculovirus, to produce an N-terminal domain of Pfs230
      (Pfs230C1).Pfs230C1 (aa 443-731) was expressed in Super Sf9 cells with a poly
      histidine affinity tag. Since the native host lacks glycosylation machinery, a
      single N585Q mutation was made to eliminate potential N-linked glycosylation. The
      expressed protein, purified by nickel affinity, ion exchange and size exclusion
      chromatography to >90% purity, was present in monomeric form, with an observed
      mass of 33,510 daltons (matching oxidized form). Peptide mapping and disulfide
      analysis confirmed the proper formation of predicted disulfide bonds.Antibodies,
      generated against Pfs230C1 in mice, bound to the gametocyte in immunofluorescence
      assay (IFA) and demonstrated functional activity in both the standard membrane
      feeding assay (SMFA) and the exflagellation assay (EXA).The biochemical,
      biophysical, and immunological results reported herein support the continued
      advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a
      transmission-blocking vaccine. Our results also support the continued use of the
      scalable baculovirus expression system for generation of complex Plasmodium
      proteins.

PMID- 28747312
TI  - "Going the extra mile" endangers doctors, patients, and NHS.

PMID- 28747313
TI  - Long-term complications, reoperations and survival following cardioverter
      defibrillator implant.
AB  - OBJECTIVE: Implantable cardioverter-defibrillators (ICDs) reduce risk of death in
      select populations, but are also associated with harms. We aimed to characterise
      long-term complications and reoperation rate. METHODS: We assessed the rate,
      cumulative incidence and predictors of long-term reoperation and survival using a
      prospective, multicentre registry serving British Columbia in Canada, a universal
      single payer healthcare system with 4.5 million residents. 3410 patients (mean
      63.3 years, 81.7% male) with new primary (n=1854) or secondary prevention
      (n=1556) ICD implant from 2003 to 2012 were followed for a median of 34 months
      (single chamber n=1069, dual chamber n=1905, biventricular n=436). Independent
      predictors of adverse outcomes were defined using Cox regression models. RESULTS:
      The overall reoperation rate was 12.0% per patient-year, and less for single vs
      dual vs biventricular ICDs (9.1% vs 12.5% vs 17.8% per patient-year,
      respectively). The Kaplan-Meier complication estimates (excluding generator end
      of life) at 1, 3 and 5 years were respectively: single chamber 10.2%, 16.2% and
      21.6%; dual 11.7%, 19.1% and 27.4% and biventricular 15.9%, 22.2% and 24.7%.
      Cardiac resynchronisation therapy had the highest rate of early lead
      complications, but lower long-term need for upgrade. Device complexity, age and
      atrial fibrillation were key determinants of complications. Overall mortality at
      1, 3 and 5 years was 5.4%, 17.4% and 32.7%, respectively. In younger patients,
      observed 5-year survival approached the expected survival in the general
      population (relative survival ratio=0.96 (0.90-0.98)). With increasing age,
      observed survival steadily declined relative to expected. CONCLUSIONS: In a
      prospective registry capturing all procedures, complication and reoperation rates
      following de novo ICD implantation were high. Shared decision making must
      carefully consider these factors.

PMID- 28747314
TI  - Severe upper abdominal pain in a 43-year-old woman.
AB  - CLINICAL INTRODUCTION: A 43-year-old healthy woman was transferred to our
      hospital due to severe upper abdominal pain during lunch. On arrival to the
      hospital she lost consciousness, had no pulse and no blood pressure; hence, the
      cardiopulmonary resuscitation was initiated and the patient was intubated.
      Echocardiography performed during the resuscitation revealed ejection fraction of
      5% with global hypokinesia. The patient was put on extracorporeal membrane
      oxygenation and was transferred to the catheterisation laboratory. The initial
      angiography and the post percutaneous coronary intervention (PCI) images are
      shown in figure 1.heartjnl;103/20/1650/F1F1F1Figure 1Images of (A) initial
      angiography and (B) post percutaneous coronary intervention. QUESTION: What is
      the diagnosis?Aortic dissectionEmboli to the left main coronary arteryPlaque
      rupture causing acute ST segment elevation myocardial infarctionSpasmSpontaneous
      coronary artery dissection.

PMID- 28747315
TI  - Renal Tubular Cell-Derived Extracellular Vesicles Accelerate the Recovery of
      Established Renal Ischemia Reperfusion Injury.
AB  - Ischemic renal injury is a complex syndrome; multiple cellular abnormalities
      cause accelerating cycles of inflammation, cellular damage, and sustained local
      ischemia. There is no single therapy that effectively resolves the renal damage
      after ischemia. However, infusions of normal adult rat renal cells have been a
      successful therapy in several rat renal failure models. The sustained broad renal
      benefit achieved by relatively few donor cells led to the hypothesis that
      extracellular vesicles (EV, largely exosomes) derived from these cells are the
      therapeutic effector in situ We now show that EV from adult rat renal tubular
      cells significantly improved renal function when administered intravenously 24
      and 48 hours after renal ischemia in rats. Additionally, EV treatment
      significantly improved renal tubular damage, 4-hydroxynanoneal adduct formation,
      neutrophil infiltration, fibrosis, and microvascular pruning. EV therapy also
      markedly reduced the large renal transcriptome drift observed after ischemia.
      These data show the potential utility of EV to limit severe renal ischemic injury
      after the occurrence.

PMID- 28747316
TI  - Mitotic nuclear pore complex segregation involves Nup2 in Aspergillus nidulans.
AB  - Transport through nuclear pore complexes (NPCs) during interphase is facilitated
      by the nucleoporin Nup2 via its importin alpha- and Ran-binding domains. However,
      Aspergillus nidulans and vertebrate Nup2 also locate to chromatin during mitosis,
      suggestive of mitotic functions. In this study, we report that Nup2 is required
      for mitotic NPC inheritance in A. nidulans Interestingly, the role of Nup2 during
      mitotic NPC segregation is independent of its importin alpha- and Ran-binding
      domains but relies on a central targeting domain that is necessary for
      localization and viability. To test whether mitotic chromatin-associated Nup2
      might function to bridge NPCs with chromatin during segregation, we provided an
      artificial link between NPCs and chromatin via Nup133 and histone H1. Using this
      approach, we bypassed the requirement of Nup2 for NPC segregation. This indicates
      that A. nidulans cells ensure accurate mitotic NPC segregation to daughter nuclei
      by linking mitotic DNA and NPC segregation via the mitotic specific chromatin
      association of Nup2.

PMID- 28747317
TI  - The risk of postoperative hemorrhage and efficacy of heparin for preventing deep
      vein thrombosis and pulmonary embolism in adult patients undergoing neurosurgery:
      a systematic review and meta-analysis.
AB  - The aim of this meta-analysis was to examine the risk of postoperative bleeding
      and efficacy of heparin for preventing deep vein thrombosis (DVT) and pulmonary
      embolism (PE) in adult patients undergoing neurosurgery. MEDLINE, Cochrane, and
      EMBASE databases were searched until October 31, 2016, for randomized controlled
      trials (RCTs) and non-randomized comparative studies that assessed the rates of
      postoperative hemorrhage, DVT, PE, and mortality in adult patients undergoing
      neurosurgery. Nine eligible studies (five RCTs, four retrospective studies)
      including 874 patients treated with either unfractionated heparin (UFH) or low
      molecular-weight heparin (LMWH) and 1033 patients in control group (placebo with
      or without compression device) were analyzed. The overall analysis revealed that
      there was an increase in the risk of postoperative hemorrhage in patients who
      received heparin (pooled OR 1.66, 95% CI 1.01 to 2.72, p=0.046) compared with no
      treatment group. The risk of postoperative hemorrhage was more significant if
      only RCTs were included in analysis. Heparin prophylaxis was associated with a
      decrease in the risk of DVT (pooled OR 0.48, 95% CI 0.36 to 0.65, p<0.001) and PE
      (pooled OR 0.25, 95% CI 0.09 to 0.73, p=0.011) but it did not affect the rate of
      mortality. In conclusion, heparin increased the rate of postoperative bleeding,
      decreased the risk of DVT, PE and venous thromboembolic event (VTE) but it did
      not affect the mortality of patients undergoing neurosurgery. For the heparin
      prophylaxis, the trade-off between the risk of postoperative bleeding and benefit
      of prophylaxis against VTEs requires further investigation.

PMID- 28747318
TI  - Attention and memory impairments in pediatric patients with cystic fibrosis and
      inflammatory bowel disease in comparison to healthy controls.
AB  - The main aim of the study was to analyze and compare attention and memory
      performance in pediatric patients with cystic fibrosis (CF), inflammatory bowel
      disease (IBD) and in healthy controls. 28 patients with CF, 30 patients with IBD
      and 30 healthy subjects took part in the study (all in age range of 7-17). All
      subjects were in intellectual norm. To analyze the functioning of attention, the
      d2 Test of Attention by Brickenkamp (d2 test) was applied. Memory performance was
      assessed using the Benton Visual Retention Test (BVRT) and the Trial of 10 words.
      The CF and IBD groups committed significantly more errors in the d2 test than the
      healthy controls. The CF group also had significantly higher fluctuation rates
      and received significantly lower scores in overall concentration performance than
      the control group. Patients with CF made more mistakes and had fewer correct
      memory projections in BVRT than the healthy controls. Patients with IBD committed
      significantly more errors in BVRT than the control group. Patients with CF and
      IBD also got significantly lower scores in the Trial of 10 words than the control
      group. Pediatric patients with CF and IBD performed more poorly than the healthy
      controls on attention and memory tests. More distinct cognitive impairments were
      observed in the CF group. Further research is needed to find the underlying
      mechanisms and clinical and/or functional significance of observed cognitive
      deficits.

PMID- 28747319
TI  - Frontline Science: A hyporesponsive subset of rat NK cells negative for Ly49s3
      and NKR-P1B are precursors to the functionally mature NKR-P1B+ subset.
AB  - Rat NK cells are divided into major subsets expressing either Ly49 receptors or
      the inhibitory NKR-P1B receptor in conjunction with NKG2A/C/E receptors. A minor
      subset of NKp46+ cells lacking expression of both Ly49 receptors and NKR-P1B is
      present in blood and spleen and is associated with decreased functional
      competence. We hypothesized that this subset may represent precursors to Ly49+
      and/or NKR-P1B+ NK cells. When cultured in vitro in IL-2 and IL-15 or adoptively
      transferred to syngeneic hosts, a portion of NKR-P1B-Ly49s3- cells transformed to
      express NKR-P1B, but very little Ly49s3. Acquisition of NKR-P1B by NKR-P1B-Ly49s3
      cells coincided with increased degranulation. In addition, although NKR-P1B
      Ly49s3- cells highly proliferate, proliferative activity was reduced upon
      acquisition of NKR-P1B at comparable levels to bona fide NKR-P1B+ NK cells. A
      fraction of NKR-P1B-Ly49s3- cells remained negative for NKR-P1B, both in vitro
      and after adoptive transfer in vivo. Most NKR-P1B-Ly49s3- cells expressed the
      transcription factor Eomesodermin and NK cell markers, indicating that these
      cells represent conventional NK cells. Our findings suggest that the NKR-P1B
      Ly49s3- NK cells are precursors to NKR-P1B single-positive cells and that
      functional competence is acquired upon expression of NKR-P1B.

PMID- 28747320
TI  - Microscopy analysis of reconstituted COPII coat polymerization and Sec16
      dynamics.
AB  - The COPII coat and the small GTPase Sar1 mediate protein export from the
      endoplasmic reticulum (ER) via specialized domains known as the ER exit sites.
      The peripheral ER protein Sec16 has been proposed to organize ER exit sites.
      However, it remains unclear how these molecules drive COPII coat polymerization.
      Here, we characterized the spatiotemporal relationships between the Saccharomyces
      cerevisiae COPII components during their polymerization by performing
      fluorescence microscopy of an artificial planar membrane. We demonstrated that
      Sar1 dissociates from the membrane shortly after the COPII coat recruitment, and
      Sar1 is then no longer required for the COPII coat to bind to the membrane.
      Furthermore, we found that Sec16 is incorporated within the COPII-cargo clusters,
      and that this is dependent on the Sar1 GTPase cycle. These data show how Sar1
      drives the polymerization of COPII coat and how Sec16 is spatially distributed
      during COPII coat polymerization.

PMID- 28747321
TI  - The Affordable Care Act Reduced Socioeconomic Disparities In Health Care Access.
AB  - The United States has the largest socioeconomic disparities in health care access
      of any wealthy country. We assessed changes in these disparities in the United
      States under the Affordable Care Act (ACA). We used survey data for the period
      2011-15 from the Behavioral Risk Factor Surveillance System to assess trends in
      insurance coverage, having a personal doctor, and avoiding medical care due to
      cost. All analyses were stratified by household income, education level,
      employment status, and home ownership status. Health care access for people in
      lower socioeconomic strata improved in both states that did expand eligibility
      for Medicaid under the ACA and states that did not. However, gains were larger in
      expansion states. The absolute gap in insurance coverage between people in
      households with annual incomes below $25,000 and those in households with incomes
      above $75,000 fell from 31 percent to 17 percent (a relative reduction of 46
      percent) in expansion states and from 36 percent to 28 percent in nonexpansion
      states (a 23 percent reduction). This serves as evidence that socioeconomic
      disparities in health care access narrowed significantly under the ACA.

PMID- 28747322
TI  - Ribonucleoprotein purification and characterization using RNA Mango.
AB  - The characterization of RNA-protein complexes (RNPs) is a difficult but
      increasingly important problem in modern biology. By combining the compact RNA
      Mango aptamer with a fluorogenic thiazole orange desthiobiotin (TO1-Dtb or TO3
      Dtb) ligand, we have created an RNA tagging system that simplifies the
      purification and subsequent characterization of endogenous RNPs. Mango-tagged RNP
      complexes can be immobilized on a streptavidin solid support and recovered in
      their native state by the addition of free biotin. Furthermore, Mango-based RNP
      purification can be adapted to different scales of RNP isolation ranging from
      pull-down assays to the isolation of large amounts of biochemically defined
      cellular RNPs. We have incorporated the Mango aptamer into the S. cerevisiae U1
      small nuclear RNA (snRNA), shown that the Mango-snRNA is functional in cells, and
      used the aptamer to pull down a U1 snRNA-associated protein. To demonstrate large
      scale isolation of RNPs, we purified and characterized bacterial RNA polymerase
      holoenzyme (HE) in complex with a Mango-containing 6S RNA. We were able to use
      the combination of a red-shifted TO3-Dtb ligand and eGFP-tagged HE to follow the
      binding and release of the 6S RNA by two-color native gel analysis as well as by
      single-molecule fluorescence cross-correlation spectroscopy. Together these
      experiments demonstrate how the Mango aptamer in conjunction with simple
      derivatives of its flurophore ligands enables the purification and
      characterization of endogenous cellular RNPs in vitro.

PMID- 28747323
TI  - Does a lung cancer screening programme promote smoking cessation?

PMID- 28747324
TI  - The personal and the organisational perspective on iatrogenic harm: bridging the
      gap through reconciliation processes.

PMID- 28747325
TI  - Simple example of a practical solution to make patient feedback more useful.

PMID- 28747326
TI  - GRAPPA-OMERACT initiative to standardise outcomes in psoriatic arthritis clinical
      trials and longitudinal observational studies.

PMID- 28747327
TI  - The extensive glycosylation of the ACPA variable domain observed for ACPA-IgG is
      absent from ACPA-IgM.

PMID- 28747328
TI  - Long-term weight-loss maintenance in obese patients with knee osteoarthritis: a
      randomized trial.
AB  - Background: A formula low-energy diet (LED) reduces weight effectively in obese
      patients with knee osteoarthritis, but the role of LED in long-term weight-loss
      maintenance is unclear.Objective: We aimed to determine the effect of
      intermittent LED compared with daily meal replacements on weight-loss maintenance
      and number of knee replacements over 3 y.Design: The design was a randomized
      trial with participants aged >50 y who had knee osteoarthritis and a body mass
      index [BMI (in kg/m2)] >=30. Participants were recruited from the osteoarthritis
      outpatient clinic at Copenhagen University Hospital in Frederiksberg, Denmark;
      they had previously completed a 68-wk lifestyle intervention trial and achieved
      an average weight loss of 10.5 kg (10% of initial body weight). Participants were
      randomly assigned to either the intermittent treatment (IN) group with LED for 5
      wk every 4 mo for 3 y or to daily meal replacements of 1-2 meals for 3 y [regular
      (RE) group]. Attention by dietitians and the amount of formula products were
      similar. Primary outcomes were changes in body weight and proportion of
      participants receiving knee replacements. Outcomes were analyzed on the intention
      to-treat-population with the use of baseline-carried-forward imputation for
      missing data.Results: A total of 153 participants (means +/- SDs: BMI: 33.3 +/-
      4.6; age: 63.8 +/- 6.3 y; 83% women) were recruited between June and December
      2009 and randomly assigned to the IN (n = 76) or RE (n = 77) group. A total of 53
      and 56 participants, respectively, completed the trial. Weight increased by 0.68
      and 1.75 kg in the IN and RE groups, respectively (mean difference: -1.06 kg; 95%
      CI: -2.75, 0.63 kg; P = 0.22). Alloplasty rates were low and did not differ (IN
      group: 8 of 76 participants; RE group: 12 of 77 participants; P =
      0.35).Conclusions: After a mean 10% weight-loss and 1-y maintenance, additional
      use of daily meal replacements or intermittent LED resulted in weight-loss
      maintenance for 3 y. These results challenge the commonly held assumption that
      weight regain in the long term is inevitable. This trial was registered at
      clinicaltrials.gov as NCT00938808.

PMID- 28747329
TI  - Bioavailability of orange juice (poly)phenols: the impact of short-term cessation
      of training by male endurance athletes.
AB  - Background: Physical exercise has been reported to increase the bioavailability
      of citrus flavanones.Objective: We investigated the bioavailability of orange
      juice (OJ) (poly)phenols in endurance-trained males before and after cessation of
      training for 7 d.Design: Ten fit, endurance-trained males, with a mean +/- SD
      maximal oxygen consumption of 58.2 +/- 5.3 mL . kg-1 . min-1, followed a low
      (poly)phenol diet for 2 d before drinking 500 mL of OJ containing 398 MUmol of
      (poly)phenols, of which 330 MUmol was flavanones. After the volunteers stopped
      training for 7 d the feeding study was repeated. Urine samples were collected 12
      h pre- and 24 h post-OJ consumption. Bioavailability was assessed by the
      quantitative analysis of urinary flavanone metabolites and (poly)phenol
      catabolites with the use of high-pressure liquid chromatography-high resolution
      mass spectrometry.Results: During training, 0-24-h urinary excretion of flavanone
      metabolites, mainly hesperetin-3'-O-glucuronide, hesperetin-3'-sulfate,
      naringenin-4'-O-glucuronide, naringenin-7-O-glucuronide, was equivalent to 4.2%
      of OJ flavanone intake. This increased significantly to 5.2% when OJ was consumed
      after the volunteers stopped training for 7 d. Overall, this trend, although not
      significant, was also observed with OJ-derived colonic catabolites, which, after
      supplementation in the trained state, were excreted in amounts equivalent to 51%
      of intake compared with 59% after cessation of training. However, urinary
      excretion of 3 colonic catabolites of bacterial origin, most notably, 3-(3'
      hydroxy-4'-methoxyphenyl)hydracrylic acid, did increase significantly when OJ was
      consumed postcessation compared with precessation of training. Data were also
      obtained on interindividual variations in flavanone bioavailability.Conclusions:
      A 7-d cessation of endurance training enhanced, rather than reduced, the
      bioavailability of OJ flavanones. The biological significance of these
      differences and whether they extend to the bioavailability of other dietary
      (poly)phenols remain to be determined. Hesperetin-3'-O-glucuronide and the
      colonic microbiota-derived catabolite 3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic
      acid are key biomarkers of the consumption of hesperetin-O-glycoside-containing
      OJ and other citrus products. This trial was registered at clinicaltrials.gov as
      NCT02627547.

PMID- 28747330
TI  - Effects of randomized whey-protein loads on energy intake, appetite, gastric
      emptying, and plasma gut-hormone concentrations in older men and women.
AB  - Background: Protein- and energy-rich supplements are used widely for the
      management of malnutrition in the elderly. Information about the effects of
      protein on energy intake and related gastrointestinal mechanisms and whether
      these differ between men and women is limited.Objective: We determined the
      effects of whey protein on energy intake, appetite, gastric emptying, and gut
      hormones in healthy older men and women.Design: Eight older women and 8 older men
      [mean +/- SEM age: 72 +/- 1 y; body mass index (in kg/m2): 25 +/- 1] were studied
      on 3 occasions in which they received protein loads of 30 g (120 kcal) or 70 g
      (280 kcal) or a flavored water control drink (0 kcal). At regular intervals over
      180 min, appetite (visual analog scales), gastric emptying (3-dimensional
      ultrasonography), and blood glucose and plasma gut-hormone concentrations
      [insulin, glucagon, ghrelin, cholecystokinin, gastric inhibitory polypeptide
      (GIP), glucagon-like peptide 1 (GLP-1), and peptide tyrosine tyrosine (PYY)] were
      measured, and ad libitum energy intake was quantified from a buffet meal (180-210
      min; energy intake, appetite, and gastric emptying in the men have been published
      previously).Results: Energy intake at the buffet meal was ~80% higher in older
      men than in older women (P < 0.001). Energy intake was not suppressed by protein
      compared with the control in men or women (P > 0.05). There was no effect of sex
      on gastric emptying, appetite, gastrointestinal symptoms, glucose, or gut
      hormones (P > 0.05). There was a protein load-dependent slowing of gastric
      emptying, an increase in concentrations of insulin, glucagon, cholecystokinin,
      GIP, GLP-1, and PYY, and an increase in total energy intake (drink plus meal: 12%
      increase with 30 g and 32% increase with 70 g; P < 0.001). Energy intake at the
      buffet meal was inversely related to the stomach volume and area under the curve
      of hormone concentrations (P < 0.05).Conclusion: In older men and women, whey
      protein drinks load-dependently slow gastric emptying and alter gut hormone
      secretion compared with a control but have no suppressive effect on subsequent ad
      libitum energy intake. This trial was registered at www.anzctr.org.au as
      ACTRN12612000941864.

PMID- 28747331
TI  - Assessing the causal role of adiposity on disordered eating in childhood,
      adolescence, and adulthood: a Mendelian randomization analysis.
AB  - Background: Observational studies have shown that higher body mass index (BMI) is
      associated with increased risk of developing disordered eating patterns. However,
      the causal direction of this relation remains ambiguous.Objective: We used
      Mendelian randomization (MR) to infer the direction of causality between BMI and
      disordered eating in childhood, adolescence, and adulthood.Design: MR analyses
      were conducted with a genetic score as an instrumental variable for BMI to assess
      the causal effect of BMI at age 7 y on disordered eating patterns at age 13 y
      with the use of data from the Avon Longitudinal Study of Parents and Children
      (ALSPAC) (n = 4473). To examine causality in the reverse direction, MR analyses
      were used to estimate the effect of the same disordered eating patterns at age 13
      y on BMI at age 17 y via a split-sample approach in the ALSPAC. We also
      investigated the causal direction of the association between BMI and eating
      disorders (EDs) in adults via a two-sample MR approach and publically available
      genome-wide association study data.Results: MR results indicated that higher BMI
      at age 7 y likely causes higher levels of binge eating and overeating, weight and
      shape concerns, and weight-control behavior patterns in both males and females
      and food restriction in males at age 13 y. Furthermore, results suggested that
      higher levels of binge eating and overeating in males at age 13 y likely cause
      higher BMI at age 17 y. We showed no evidence of causality between BMI and EDs in
      adulthood in either direction.Conclusions: This study provides evidence to
      suggest a causal effect of higher BMI in childhood and increased risk of
      disordered eating at age 13 y. Furthermore, higher levels of binge eating and
      overeating may cause higher BMI in later life. These results encourage an
      exploration of the ways to break the causal chain between these complex
      phenotypes, which could inform and prevent disordered eating problems in
      adolescence.

PMID- 28747332
TI  - Community hospitals: still a viable option?

PMID- 28747333
TI  - E-cigarette use and associated changes in population smoking cessation: evidence
      from US current population surveys.
AB  - Objective To examine whether the increase in use of electronic cigarettes in the
      USA, which became noticeable around 2010 and increased dramatically by 2014, was
      associated with a change in overall smoking cessation rate at the population
      level.Design Population surveys with nationally representative samples.Setting
      Five of the US Current Population Survey-Tobacco Use Supplement (CPS-TUS) in 2001
      02, 2003, 2006-07, 2010-11, and 2014-15.Participants Data on e-cigarette use were
      obtained from the total sample of the 2014-15 CPS-TUS (n=161 054). Smoking
      cessation rates were obtained from those who reported smoking cigarettes 12
      months before the survey (n=23 270). Rates from 2014-15 CPS-TUS were then
      compared with those from 2010-11 CPS-TUS (n=27 280) and those from three other
      previous surveys.Main outcome measures Rate of attempt to quit cigarette smoking
      and the rate of successfully quitting smoking, defined as having quit smoking for
      at least three months.Results Of 161 054 respondents to the 2014-15 survey, 22
      548 were current smokers and 2136 recent quitters. Among them, 38.2% of current
      smokers and 49.3% of recent quitters had tried e-cigarettes, and 11.5% and 19.0%
      used them currently (every day or some days). E-cigarette users were more likely
      than non-users to attempt to quit smoking, 65.1% v 40.1% (change=25.0%, 95%
      confidence interval 23.2% to 26.9%), and more likely to succeed in quitting, 8.2%
      v 4.8% (3.5%, 2.5% to 4.5%). The overall population cessation rate for 2014-15
      was significantly higher than that for 2010-11, 5.6% v 4.5% (1.1%, 0.6% to 1.5%),
      and higher than those for all other survey years (range 4.3-4.5%).Conclusion The
      substantial increase in e-cigarette use among US adult smokers was associated
      with a statistically significant increase in the smoking cessation rate at the
      population level. These findings need to be weighed carefully in regulatory
      policy making regarding e-cigarettes and in planning tobacco control
      interventions.

PMID- 28747334
TI  - PEDF expression affects retinal endothelial cell proangiogenic properties through
      alterations in cell adhesive mechanisms.
AB  - Pigment epithelium-derived factor (PEDF) is an endogenous inhibitor of
      angiogenesis. Although various ocular cell types including retinal endothelial
      cells (EC) produce PEDF, we know very little about cell autonomous effects of
      PEDF in these cell types. Here we determined how PEDF expression affects retinal
      EC proangiogenic properties. Retinal EC were prepared from wild-type (PEDF+/+)
      and PEDF-deficient (PEDF-/-) mice. The identity of EC was confirmed by staining
      for specific markers including vascular endothelial cadherin, CD31, and B4
      lectin. Retinal EC also expressed VEGF receptor 1 and endoglin, as well as ICAM
      1, ICAM-2, and VCAM-1. PEDF-/- retinal EC were more proliferative, less apoptotic
      when challenged with H2O2, less migratory, and less adherent compared with
      PEDF+/+ EC. These changes could be associated, at least in part, with increased
      levels of tenascin-C, fibronectin, thrombospondin-1 and collagen IV, and lower
      amounts of osteopontin. PEDF-/- EC also exhibited alterations in expression of a
      number of integrins including alpha2, alphav, beta1, beta8, and alphavbeta3, and
      cell-cell adhesion molecules including CD31, zonula occluden-1, and occludin.
      These observations correlated with attenuation of capillary morphogenesis and
      increased levels of oxidative stress in PEDF-/- EC. PEDF-/- EC also produced
      lower levels of VEGF compared with PEDF+/+ cells. Thus, PEDF deficiency has a
      significant impact on retinal EC adhesion and migration, perhaps through altered
      production of extracellular matrix and junctional proteins in response to
      increased oxidative stress affecting their proangiogenic activity.

PMID- 28747336
TI  - An innovative intermittent hypoxia model for cell cultures allowing fast Po2
      oscillations with minimal gas consumption.
AB  - Performing hypoxia-reoxygenation cycles in cell culture with a cycle duration
      accurately reflecting what occurs in obstructive sleep apnea (OSA) patients is a
      difficult but crucial technical challenge. Our goal was to develop a novel device
      to expose multiple cell culture dishes to intermittent hypoxia (IH) cycles
      relevant to OSA with limited gas consumption. With gas flows as low as 200
      ml/min, our combination of plate holders with gas-permeable cultureware generates
      rapid normoxia-hypoxia cycles. Cycles alternating 1 min at 20% O2 followed by 1
      min at 2% O2 resulted in Po2 values ranging from 124 to 44 mmHg. Extending
      hypoxic and normoxic phases to 10 min allowed Po2 variations from 120 to 25 mmHg.
      The volume of culture medium or the presence of cells only modestly affected the
      Po2 variations. In contrast, the nadir of the hypoxia phase increased when
      measured at different heights above the membrane. We validated the physiological
      relevance of this model by showing that hypoxia inducible factor-1alpha
      expression was significantly increased by IH exposure in human aortic endothelial
      cells, murine breast carcinoma (4T1) cells as well as in a blood-brain barrier
      model (2.5-, 1.5-, and 6-fold increases, respectively). In conclusion, we have
      established a new device to perform rapid intermittent hypoxia cycles in cell
      cultures, with minimal gas consumption and the possibility to expose several
      culture dishes simultaneously. This device will allow functional studies of the
      consequences of IH and deciphering of the molecular biology of IH at the cellular
      level using oxygen cycles that are clinically relevant to OSA.

PMID- 28747335
TI  - Cross talk between increased intracellular zinc (Zn2+) and accumulation of
      reactive oxygen species in chemical ischemia.
AB  - Both zinc (Zn2+) and reactive oxygen species (ROS) have been shown to accumulate
      during hypoxic-ischemic stress and play important roles in pathological
      processes. To understand the cross talk between the two of them, here we studied
      Zn2+ and ROS accumulation by employing fluorescent probes in HeLa cells to
      further the understanding of the cause and effect relationship of these two
      important cellular signaling systems during chemical-ischemia, stimulated by
      oxygen and glucose deprivation (OGD). We observed two Zn2+ rises that were
      divided into four phases in the course of 30 min of OGD. The first Zn2+ rise was
      a transient, which was followed by a latent phase during which Zn2+ levels
      recovered; however, levels remained above a basal level in most cells. The final
      phase was the second Zn2+ rise, which reached a sustained plateau called Zn2+
      overload. Zn2+ rises were not observed when Zn2+ was removed by TPEN (a Zn2+
      chelator) or thapsigargin (depleting Zn2+ from intracellular stores) treatment,
      indicating that Zn2+ was from intracellular storage. Damaging mitochondria with
      FCCP significantly reduced the second Zn2+ rise, indicating that the
      mitochondrial Zn2+ accumulation contributes to Zn2+ overload. We also detected
      two OGD-induced ROS rises. Two Zn2+ rises preceded two ROS rises. Removal of Zn2+
      reduced or delayed OGD- and FCCP-induced ROS generation, indicating that Zn2+
      contributes to mitochondrial ROS generation. There was a Zn2+-induced increase in
      the functional component of NADPH oxidase, p47phox, thus suggesting that NADPH
      oxidase may mediate Zn2+-induced ROS accumulation. We suggest a new mechanism of
      cross talk between Zn2+ and mitochondrial ROS through positive feedback processes
      that eventually causes excessive free Zn2+ and ROS accumulations during the
      course of ischemic stress.

PMID- 28747337
TI  - Comparisons of external fixator combined with limited internal fixation and open
      reduction and internal fixation for Sanders type 2 calcaneal fractures: Finite
      element analysis and clinical outcome.
AB  - OBJECTIVES: The aim of this study was to compare the biomechanical stability and
      clinical outcome of external fixator combined with limited internal fixation
      (EFLIF) and open reduction and internal fixation (ORIF) in treating Sanders type
      2 calcaneal fractures. METHODS: Two types of fixation systems were selected for
      finite element analysis and a dual cohort study. Two fixation systems were
      simulated to fix the fracture in a finite element model. The relative
      displacement and stress distribution were analysed and compared. A total of 71
      consecutive patients with closed Sanders type 2 calcaneal fractures were enrolled
      and divided into two groups according to the treatment to which they chose: the
      EFLIF group and the ORIF group. The radiological and clinical outcomes were
      evaluated and compared. RESULTS: The relative displacement of the EFLIF was less
      than that of the plate (0.1363 mm to 0.1808 mm). The highest von Mises stress
      value on the plate was 33% higher than that on the EFLIF. A normal restoration of
      the Bohler angle was achieved in both groups. No significant difference was found
      in the clinical outcome on the American Orthopedic Foot and Ankle Society Ankle
      Hindfoot Scale, or on the Visual Analogue Scale between the two groups (p >
      0.05). Wound complications were more common in those who were treated with ORIF
      (p = 0.028). CONCLUSIONS: Both EFLIF and ORIF systems were tested to 160 N
      without failure, showing the new construct to be mechanically safe to use. Both
      EFLIF and ORIF could be effective in treating Sanders type 2 calcaneal fractures.
      The EFLIF may be superior to ORIF in achieving biomechanical stability and less
      blood loss, shorter surgical time and hospital stay, and fewer wound
      complications.Cite this article: M. Pan, L. Chai, F. Xue, L. Ding, G. Tang, B.
      Lv. Comparisons of external fixator combined with limited internal fixation and
      open reduction and internal fixation for Sanders type 2 calcaneal fractures:
      Finite element analysis and clinical outcome. Bone Joint Res 2017;6:433-438. DOI:
      10.1302/2046-3758.67.2000640.

PMID- 28747338
TI  - Copy number loss in the region of the ASPN gene in patients with acetabular
      dysplasia: ASPN CNV in acetabular dysplasia.
AB  - OBJECTIVES: We have previously investigated an association between the genome
      copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is
      associated with a genetic polymorphism in the aspartic acid repeat in the N
      terminal region of the asporin (ASPN) gene; therefore, the present study aimed to
      investigate whether the CNV of ASPN is involved in the pathogenesis of AD.
      METHODS: Acetabular coverage of all subjects was evaluated using radiological
      findings (Sharp angle, centre-edge (CE) angle, acetabular roof obliquity (ARO)
      angle, and minimum joint space width). Genomic DNA was extracted from peripheral
      blood leukocytes. Agilent's region-targeted high-density oligonucleotide tiling
      microarray was used to analyse 64 female AD patients and 32 female control
      subjects. All statistical analyses were performed using EZR software (Fisher's
      exact probability test, Pearson's correlation test, and Student's t-test).
      RESULTS: CNV analysis of the ASPN gene revealed a copy number loss in
      significantly more AD patients (9/64) than control subjects (0/32; p = 0.0212).
      This loss occurred within a 60 kb region on 9q22.31, which harbours the gene for
      ASPN. The mean radiological parameters of these AD patients were significantly
      worse than those of the other subjects (Sharp angle, p = 0.0056; CE angle, p =
      0.0076; ARO angle, p = 0.0065), and all nine patients required operative therapy
      such as total hip arthroplasty or pelvic osteotomy. Moreover, six of these nine
      patients had a history of operative or conservative therapy for developmental
      dysplasia of the hip. CONCLUSIONS: Copy number loss within the region harbouring
      the ASPN gene on 9q22.31 is associated with severe AD. A copy number loss in the
      ASPN gene region may play a role in the aetiology of severe AD.Cite this article:
      T. Sekimoto, M. Ishii, M. Emi, S. Kurogi, T. Funamoto, Y. Yonezawa, T. Tajima, T.
      Sakamoto, H. Hamada, E. Chosa. Copy number loss in the region of the ASPN gene in
      patients with acetabular dysplasia: ASPN CNV in acetabular dysplasia. Bone Joint
      Res 2017;6:439-445. DOI: 10.1302/2046-3758.67.BJR-2016-0094.R1.

PMID- 28747339
TI  - Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by
      The Cancer Genome Atlas Project.
AB  - Purpose: The Cancer Genome Atlas (TCGA) project recently uncovered four molecular
      subtypes of gastric cancer: Epstein-Barr virus (EBV), microsatellite instability
      (MSI), genomically stable (GS), and chromosomal instability (CIN). However, their
      clinical significances are currently unknown. We aimed to investigate the
      relationship between subtypes and prognosis of patients with gastric
      cancer.Experimental Design: Gene expression data from a TCGA cohort (n = 262)
      were used to develop a subtype prediction model, and the association of each
      subtype with survival and benefit from adjuvant chemotherapy was tested in 2
      other cohorts (n = 267 and 432). An integrated risk assessment model (TCGA risk
      score) was also developed.Results: EBV subtype was associated with the best
      prognosis, and GS subtype was associated with the worst prognosis. Patients with
      MSI and CIN subtypes had poorer overall survival than those with EBV subtype but
      better overall survival than those with GS subtype (P = 0.004 and 0.03 in two
      cohorts, respectively). In multivariate Cox regression analyses, TCGA risk score
      was an independent prognostic factor [HR, 1.5; 95% confidence interval (CI), 1.2
      1.9; P = 0.001]. Patients with the CIN subtype experienced the greatest benefit
      from adjuvant chemotherapy (HR, 0.39; 95% CI, 0.16-0.94; P = 0.03) and those with
      the GS subtype had the least benefit from adjuvant chemotherapy (HR, 0.83; 95%
      CI, 0.36-1.89; P = 0.65).Conclusions: Our prediction model successfully
      stratified patients by survival and adjuvant chemotherapy outcomes. Further
      development of the prediction model is warranted. Clin Cancer Res; 23(15); 1-9.
      (c)2017 AACR.

PMID- 28747340
TI  - Epithelial TNF Receptor Signaling Promotes Mucosal Repair in Inflammatory Bowel
      Disease.
AB  - TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by
      the dramatic therapeutic responses in Crohn's disease (CD) patients induced by
      chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a
      decoy receptor that binds soluble TNF, fails to improve disease. To explore this
      discrepancy, we investigated the role of TNF signaling in Wnt/beta-catenin
      mediated intestinal stem cell and progenitor cell expansion in CD patients, human
      cells, and preclinical mouse models. We hypothesized that TNF exerts beneficial
      effects on intestinal epithelial cell (IEC) responses to injury. In CD patients,
      intestinal stem cell and progenitor cell Wnt/beta-catenin signaling correlates
      with inflammation status. TNF-deficient (Tnf-/-) mice exhibited increased
      apoptosis, less IEC proliferation, and less Wnt signaling when stimulated with
      anti-CD3 mAb. Bone marrow (BM) chimera mice revealed that mucosal repair depended
      on TNF production by BM-derived cells and TNFR expression by radioresistant IECs.
      Wild-type->Tnfr1/2-/- BM chimera mice with chronic dextran sodium sulfate colitis
      exhibited delayed ulcer healing, more mucosal inflammation, and impaired Wnt/beta
      catenin signaling, consistent with the hypothesis that epithelial TNFR signaling
      participates in mucosal healing. The direct effect of TNF on stem cells was
      demonstrated by studies of TNF-induced Wnt/beta-catenin target gene expression in
      murine enteroids and colonoid cultures and TNF-induced beta-catenin activation in
      nontransformed human NCM460 cells (TOPFlash) and mice (TOP-GAL). Together, these
      data support the hypothesis that TNF plays a beneficial role in enhancing
      Wnt/beta-catenin signaling during ulcer healing in IBD. These novel findings will
      inform clinicians and therapeutic chemists alike as they strive to develop novel
      therapies for IBD patients.

PMID- 28747341
TI  - Arginase1 Deficiency in Monocytes/Macrophages Upregulates Inducible Nitric Oxide
      Synthase To Promote Cutaneous Contact Hypersensitivity.
AB  - The innate immune components that modulate allergic contact hypersensitivity
      (CHS) responses are poorly defined. Using human skin from contact dermatitis
      patients and a mouse model of CHS, we find that hapten allergens disrupt the
      Arginase1 (Arg1) and inducible NO synthase (iNOS) dynamic in
      monocytes/macrophages (mono/MPhi), which renders those cells ineffectual in
      suppressing skin inflammation. Mice lacking Arg1 in MPhi develop increased CHS
      characterized by elevated ear thickening, mono/MPhi-dominated dermal
      inflammation, and increased iNOS and IL-6 expression compared with control mice.
      Treatment of Arg1flox/flox; LysMCre+/- mice with a selective NOS inhibitor or
      knockout of Nos2, encoding iNOS, significantly ameliorates CHS. Our findings
      suggest a critical role for Arg1 in mono/MPhi in suppressing CHS through
      dampening Nos2 expression. These results support that increasing Arg1 may be a
      potential therapeutic avenue in treating allergic contact dermatitis.

PMID- 28747342
TI  - sIgM-FcMUR Interactions Regulate Early B Cell Activation and Plasma Cell
      Development after Influenza Virus Infection.
AB  - Previous studies with mice lacking secreted IgM (sIgM) due to a deletion of the
      MUs splice region (MUs-/- ) had shown sIgM involvement in normal B cell
      development and in support of maximal Ag-specific IgG responses. Because of the
      changes to B cell development, it remains unclear to which extent and how sIgM
      directly affects B cell responses. In this study, we aimed to explore the
      underlying mechanisms of sIgM-mediated IgG response regulation during influenza
      virus infection. Generating mice with normally developed MUs-deficient B cells,
      we demonstrate that sIgM supports IgG responses by enhancing early Ag-specific B
      cell expansion, not by altering B cell development. Lack of FcMUR expression on B
      cells, but not lack of Fcalpha/MUR expression or complement activation, reduced
      antiviral IgG responses to the same extent as observed in MUs-/- mice. B cell
      specific Fcmr-/- mice lacked robust clonal expansion of influenza hemagglutinin
      specific B cells early after infection and developed fewer spleen and bone marrow
      IgG plasma cells and memory B cells, compared with controls. However, germinal
      center responses appeared unaffected. Provision of sIgM rescued plasma cell
      development from MUs-/- but not Fcmr-/- B cells, as demonstrated with mixed bone
      marrow chimeric mice. Taken together, the data suggest that sIgM interacts with
      FcMUR on B cells to support early B cell activation and the development of long
      lived humoral immunity.

PMID- 28747343
TI  - The Development of Steady-State Activation Hubs between Adult LTi ILC3s and
      Primed Macrophages in Small Intestine.
AB  - Group 3 innate lymphoid cells (ILC3s) are important for intestinal health,
      particularly in controlling inflammation in response to epithelial dysregulation,
      but their role during homeostasis remains less well understood. We generated IL
      22 reporter mice to assess production of this key cytokine by ILC3s in the small
      intestine during development and under basal conditions. Although IL-22 is
      produced by a variety of lymphocyte populations, constitutively high IL-22
      expression was limited to lymphoid-tissue inducer (LTi) cells residing in lymph
      node-like structures in the gut called solitary intestinal lymphoid tissues
      (SILT). Constitutive IL-22 expression was dependent on the microbiota and MyD88
      signaling, appeared upon weaning, and was present across the spectrum of SILT,
      including in cryptopatches. Activated SILT LTi cells colocalized with a rare
      subpopulation of activated macrophages constitutively positive for IL-12/23 p40
      and capable of activating neonatal LTi cells in response to TLR stimulus. Thus,
      weaning leads to the organization of innate immune activation hubs at SILT that
      mature and are continuously sustained by signals from the microbiota. This
      functional and anatomic organization constitutes a significant portion of the
      steady-state IL-23/IL-22 axis.

PMID- 28747344
TI  - The Small Rho GTPase TC10 Modulates B Cell Immune Responses.
AB  - Rho family GTPases regulate diverse cellular events, such as cell motility,
      polarity, and vesicle traffic. Although a wealth of data exists on the canonical
      Rho GTPases RhoA, Rac1, and Cdc42, several other family members remain poorly
      studied. In B cells, we recently demonstrated a critical role for Cdc42 in plasma
      cell differentiation. In this study, we focus on a close homolog of Cdc42, TC10
      (also known as RhoQ), and investigate its physiological role in B cells. By
      generating a TC10-deficient mouse model, we show that despite reduced total B
      cell numbers, B cell development in these mice occurs normally through distinct
      developmental stages. Upon immunization, IgM levels were reduced and, upon viral
      infection, germinal center responses were defective in TC10-deficient mice. BCR
      signaling was mildly affected, whereas cell migration remained normal in TC10
      deficient B cells. Furthermore, by generating a TC10/Cdc42 double knockout mouse
      model, we found that TC10 can compensate for the lack of Cdc42 in TLR-induced
      cell activation and proliferation, so the two proteins play partly redundant
      roles. Taken together, by combining in vivo and in vitro analysis using TC10
      deficient mice, we define the poorly studied Rho GTPase TC10 as an
      immunomodulatory molecule playing a role in physiological B cell responses.

PMID- 28747345
TI  - ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6alpha-Endoplasmic
      Reticulum Stress-Beclin1 Autophagy Regulatory Pathway.
AB  - The genetic association of orosomucoid-like 3 (ORMDL3) with an array of
      immunoinflammatory disorders has been recently unraveled in multiple ethnic
      groups, and functional exploration has received attention of the particular
      relevance of this gene in endoplasmic reticulum stress, lipid metabolism, and
      inflammatory response. In this study, we demonstrated the upregulation of ORMDL3
      in both patients with systemic lupus erythematosus and lupus mice compared with
      controls. By establishing ORMDL3 knockout mice (Ormdl3-/-), we showed that
      silencing Ormdl3 in vivo significantly decreased the proportions of mature B
      lymphocytes and transitional 2B cells in spleen and B1a cells from abdominal
      cavity perfusion fluid, the secretion of IgG and IgM, and the expression of Baff.
      Additionally, knockdown of Ormdl3 augmented the apoptosis of total splenic cells
      and splenic CD19+ B cells but did not affect B cell proliferation and cell cycle.
      Subsequently, we in vitro and in vivo demonstrated that ORMDL3 potentially
      mediates the autophagy via the ATF 6-Beclin1 autophagy pathway, and it
      facilitates the survival of splenic B cells via promoting autophagy and
      suppressing apoptosis. Taken together, we uncovered a role of ORMDL3 in fine
      tuning B cell development and survival, besides highlighting a potential
      mechanism by which ORMDL3 regulates autophagy via ATF6 pathway.

PMID- 28747346
TI  - Modulation of Roquin Function in Myeloid Cells Reduces Mycobacterium tuberculosis
      Induced Inflammation.
AB  - Damaging inflammation is a hallmark of Mycobacterium tuberculosis infection, and
      understanding how this is regulated is important for the development of new
      therapies to limit excessive inflammation. The E3 ubiquitin ligase, Roquin, is
      involved in immune regulation; however, its role in immunity to M. tuberculosis
      is unknown. To address this, we infected mice with a point mutation in
      Roquin1/Rc3h1 (sanroque). Aerosol-infected sanroque mice showed enhanced control
      of M. tuberculosis infection associated with delayed bacterial dissemination and
      upregulated TNF production in the lungs after 2 wk. However, this early control
      of infection was not maintained, and by 8 wk postinfection sanroque mice
      demonstrated an increased bacterial burden and dysregulated inflammation in the
      lungs. As the inflammation in the lungs of the sanroque mice could have been
      influenced by emerging autoimmune conditions that are characteristic of the mice
      aging, the function of Roquin was examined in immune cell subsets in the absence
      of autoimmune complications. M. bovis bacillus Calmette-Guerin-primed sanroque T
      cells transferred into Rag1-/- mice provided equivalent protection in the spleen
      and liver. Interestingly, the transfer of mycobacteria-specific (P25 CD4+ TCR
      transgenic) wild-type spleen cells into sanroqueRag1-/- mice actually led to
      enhanced protection with reduced bacterial load, decreased chemokine expression,
      and reduced inflammation in the lungs compared with transfers into Rag1-/- mice
      expressing intact Roquin. These studies suggest that modulation of Roquin in
      myeloid cells may reduce both inflammation and bacterial growth during the
      chronic phase of M. tuberculosis infection.

PMID- 28747347
TI  - TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking
      TRIF-TBK1 Interaction.
AB  - TLR-mediated signaling pathways play critical roles in host defense against
      microbials. However, dysregulation of innate immune and inflammatory responses
      triggered by TLRs would result in harmful damage to the host. Using a Trim8 gene
      knockout mouse model, we show that tripartite motif (TRIM) 8 negatively regulates
      TLR3- and TLR4-mediated innate immune and inflammatory responses. TRIM8
      deficiency leads to increased polyinosinic-polycytidylic acid- and LPS-triggered
      induction of downstream anti-microbial genes including TNF, Il6, Rantes, and
      Ifnb, evaluated serum cytokine levels, and increased susceptibility of mice to
      polyinosinic-polycytidylic acid- and LPS-induced inflammatory death as well as
      Salmonella typhimurium infection-induced loss of body weight and septic shock.
      TRIM8 interacted with Toll/IL-1 receptor domain-containing adapter-inducing IFN
      beta and mediated its K6- and K33-linked polyubiquitination, leading to
      disruption of the Toll/IL-1 receptor domain-containing adapter-inducing IFN-beta
      TANK-binding kinase-1 association. Our findings uncover an additional mechanism
      on the termination of TLR3/4-mediated inflammatory and innate immune responses.

PMID- 28747348
TI  - Lactation-Based Maternal Educational Immunity Crosses MHC Class I Barriers and
      Can Impart Th1 Immunity to Th2-Biased Recipients.
AB  - We have previously demonstrated lactational transfer of T cell-based immunity
      from dam to foster pup. In the short term, a significant part of transferred
      immunity is passive cellular immunity. However, as time progresses, this is
      replaced by what we have described as maternal educational immunity such that by
      young adulthood, all immune cells responding to a foster dam immunogen are the
      product of the foster pup's thymus. To reduce confounding factors, this original
      demonstration used congenic/syngeneic dam and foster pup pairs. In this study, we
      investigated lactational transfer of immunity to Mycobacterium tuberculosis in
      MHC class I-mismatched animals, as well as from Th1-biased dams to Th2-biased
      foster pups. Using immunized C57BL/6J dams, lactational transfer to nonimmunized
      BALB/cJ foster pups resulted in much greater immunity than direct immunization in
      5-wk-old pups (ex vivo assay of pup splenocytes). At this age, 82% of immunogen
      responding cells in the pup spleen were produced through maternal educational
      immunity. FVB/NJ nonimmunized foster recipients had a greater number of maternal
      cells in the spleen and thymus but a much larger percentage was Foxp3+, resulting
      in equivalent immunity to direct immunization. Depletion of maternal Foxp3+ cells
      from pup splenocytes illustrated a substantial role for lactationally transferred
      dam regulatory T cells in suppression of the ex vivo response in FVB/NJ, but not
      BALB/cJ, recipients. We conclude that lactational transfer of immunity can cross
      MHC class I barriers and that Th1 immunity can be imparted to Th2-biased
      offspring; in some instances, it can be greater than that achieved by direct
      immunization.

PMID- 28747349
TI  - Outcomes associated with a pediatric clinical diabetes network in Ontario: a
      population-based time-trend analysis.
AB  - BACKGROUND: The Network of Ontario Pediatric Diabetes Programs was implemented in
      2001. The objective of this study was to determine whether implementation of the
      network was associated with a decrease in the risk of acute diabetes-related
      complications and a reduction in the socioeconomic and geographic disparities in
      these outcomes. METHODS: We conducted a population-based time trend analysis of
      children (< 18 yr) with diabetes using health administrative databases in Ontario
      from 1996 to 2011. We determined the relation between network implementation and
      diabetes-related emergency department visits and hospital admissions using linear
      mixed-effects models with a Poisson link function. RESULTS: Data for 13 806
      children with established diabetes were analyzed. After the network was
      implemented, there was a significant decrease in the rate per 100 children of
      emergency department visits (17.0 in 2001 v. 10.00 in 2011, p < 0.001) and
      hospital admissions (8.8 v. 5.0, p < 0.001). The decrease was most significant
      for those in the lowest socioeconomic quintile and in urban areas. After network
      implementation, children in the lowest socioeconomic quintile remained at higher
      risk than those in the highest socioeconomic quintile for emergency department
      visits (adjusted rate ratio [RRafter] 1.77 [95% confidence interval (CI) 1.55 to
      2.03]) and hospital admissions (RRafter 2.11 [95% CI 1.77 to 2.52]). However, the
      yearly decrease in rates of emergency department visits and hospital admissions
      for the lowest compared to the highest socioeconomic quintile shifted toward a
      decreasing disparity after network implementation (p < 0.05). Before the network
      was implemented, geographic location was not associated with outcomes. After
      implementation, the risk of emergency department visits among patients from urban
      areas was significantly lower than that among patients from rural areas.
      INTERPRETATION: The establishment of a pediatric diabetes network was associated
      with better health outcomes, particularly for patients of lower socioeconomic
      status. Further work is needed to address the health care needs of those in rural
      areas.

PMID- 28747350
TI  - Urinary tract infection in the very young: can we avoid voiding cystography?

PMID- 28747351
TI  - Insights from Small-N Studies.

PMID- 28747352
TI  - Increasing Research Productivity in Undergraduate Research Experiences: Exploring
      Predictors of Collaborative Faculty-Student Publications.
AB  - Little attention has been paid to understanding faculty-student productivity via
      undergraduate research from the faculty member's perspective. This study examines
      predictors of faculty-student publications resulting from mentored undergraduate
      research, including measures of faculty-student collaboration, faculty commitment
      to undergraduate students, and faculty characteristics. Generalized estimating
      equations were used to analyze data from 468 faculty members across 13 research
      intensive institutions, collected by a cross-sectional survey in 2013/2014.
      Results show that biomedical faculty mentors were more productive in publishing
      collaboratively with undergraduate students when they worked with students for
      more than 1 year on average, enjoyed teaching students about research, had
      mentored Black students, had received more funding from the National Institutes
      of Health, had a higher H-index scores, and had more years of experience working
      in higher education. This study suggests that college administrators and research
      program directors should strive to create incentives for faculty members to
      collaborate with undergraduate students and promote faculty awareness that
      undergraduates can contribute to their research.

PMID- 28747353
TI  - Effectiveness of a Low-Cost, Graduate Student-Led Intervention on Study Habits
      and Performance in Introductory Biology.
AB  - Institutions have developed diverse approaches that vary in effectiveness and
      cost to improve student performance in introductory science, technology,
      engineering, and mathematics courses. We developed a low-cost, graduate student
      led, metacognition-based study skills course taught in conjunction with the
      introductory biology series at Miami University. Our approach aimed to improve
      performance for underachieving students by combining an existing framework for
      the process of learning (the study cycle) with concrete tools (outlines and
      concept maps) that have been shown to encourage deep understanding. To assess the
      effectiveness of our efforts, we asked 1) how effective our voluntary recruitment
      model was at enrolling the target cohort, 2) how the course impacted performance
      on lecture exams, 3) how the course impacted study habits and techniques, and 4)
      whether there are particular study habits or techniques that are associated with
      large improvements on exam scores. Voluntary recruitment attracted only 11-17% of
      our target cohort. While focal students improved on lecture exams relative to
      their peers who did not enroll, gains were relatively modest, and not all
      students improved. Further, although students across both semesters of our study
      reported improved study habits (based on pre and post surveys) and on outlines
      and concept maps (based on retrospectively scored assignments), gains were more
      dramatic in the Fall semester. Multivariate models revealed that, while changes
      in study habits and in the quality of outlines and concept maps were weakly
      associated with change in performance on lecture exams, relationships were only
      significant in the Fall semester and were sometimes counterintuitive. Although
      benefits of the course were offset somewhat by the inefficiency of voluntary
      recruitment, we demonstrate the effectiveness our course, which is inexpensive to
      implement and has advantage of providing pedagogical experience to future
      educators.

PMID- 28747354
TI  - Mentoring Interventions for Underrepresented Scholars in Biomedical and
      Behavioral Sciences: Effects on Quality of Mentoring Interactions and
      Discussions.
AB  - Mentors rarely receive education about the unique needs of underrepresented
      scholars in the biomedical and behavioral sciences. We hypothesized that mentor
      training and peer-mentoring interventions for these scholars would enrich the
      perceived quality and breadth of discussions between mentor-protege dyads (i.e.,
      mentor-protege pairs). Our multicenter, randomized study of 150 underrepresented
      scholar-mentor dyads compared: 1) mentor training, 2) protege peer mentoring, 3)
      combined mentor training and peer mentoring, and 4) a control condition (i.e.,
      usual practice of mentoring). In this secondary analysis, the outcome variables
      were quality of dyad time and breadth of their discussions. Protege participants
      were graduate students, fellows, and junior faculty in behavioral and biomedical
      research and healthcare. Dyads with mentor training were more likely than those
      without mentor training to have discussed teaching and work-life balance. Dyads
      with peer mentoring were more likely than those without peer mentoring to have
      discussed clinical care and career plans. The combined intervention dyads were
      more likely than controls to perceive that the quality of their time together was
      good/excellent. Our study supports the value of these mentoring interventions to
      enhance the breadth of dyad discussions and quality of time together, both
      important components of a good mentoring relationship.

PMID- 28747355
TI  - The Math-Biology Values Instrument: Development of a Tool to Measure Life Science
      Majors' Task Values of Using Math in the Context of Biology.
AB  - In response to calls to improve the quantitative training of undergraduate
      biology students, there have been increased efforts to better integrate math into
      biology curricula. One challenge of such efforts is negative student attitudes
      toward math, which are thought to be particularly prevalent among biology
      students. According to theory, students' personal values toward using math in a
      biological context will influence their achievement and behavioral outcomes, but
      a validated instrument is needed to determine this empirically. We developed the
      Math-Biology Values Instrument (MBVI), an 11-item college-level self--report
      instrument grounded in expectancy-value theory, to measure life science students'
      interest in using math to understand biology, the perceived usefulness of math to
      their life science career, and the cost of using math in biology courses. We used
      a process that integrates multiple forms of validity evidence to show that scores
      from the MBVI can be used as a valid measure of a student's value of math in the
      context of biology. The MBVI can be used by instructors and researchers to help
      identify instructional strategies that influence math-biology values and
      understand how math-biology values are related to students' achievement and
      decisions to pursue more advanced quantitative-based courses.

PMID- 28747356
TI  - Improving Exam Performance in Introductory Biology through the Use of Preclass
      Reading Guides.
AB  - High-structure courses or flipped courses require students to obtain course
      content before class so that class time can be used for active-learning
      exercises. While textbooks are used ubiquitously in college biology courses for
      content dissemination, studies have shown that students frequently do not read
      their textbooks. To address this issue, we created preclass reading guides that
      provided students with a way to actively engage with the required reading for
      each day of class. To determine whether reading guide completion before class is
      associated with increased performance, we surveyed students about their use of
      reading guides in two sections of a large-enrollment (400+ students) introductory
      biology course and used multiple linear regression models to identify significant
      correlations. The results indicated that greater than 80% of students completed
      the reading guides before class and that full completion of the reading guides
      before class was significantly positively correlated with exam performance.
      Reading guides in most cases were used similarly between different student groups
      (based on gender, ethnicity, and aptitude). These results suggest that optional
      preclass reading guides may help students stay on track to acquire course content
      in introductory biology and thus result in improved exam performance.

PMID- 28747357
TI  - An inhibitor of histone deacetylase 6 activity, ACY-1215, reduces cAMP and cyst
      growth in polycystic kidney disease.
AB  - Adult-onset autosomal-dominant polycystic kidney disease (ADPKD) is caused by
      mutations in either the PKD1 or PKD2 gene, leading to malfunction of their gene
      products, polycystin 1 or 2. Histone deacetylase 6 (HDAC6) expression and
      activity are increased in PKD1 mutant renal epithelial cells. Here we studied the
      effect of ACY-1215, a specific HDAC6 inhibitor, on cyst growth in ADPKD.
      Treatment with ACY-1215 slowed cyst growth in a mouse model of ADPKD that forms
      massive cysts within 3 wk after knockout of polycystin 1 function. It also
      prevented cyst formation in MDCK.2 cells, an in vitro model of cystogenesis, and
      in an ADPKD cell line derived from the proximal tubules from a pkd1-/-.mouse (PN
      cells). In PN cells ACY-1215 also reduced the size of already established cysts.
      We found that ACY-1215 lowered cAMP levels and protein expression of adenylyl
      cyclase 6. Our results suggest that HDAC6 could potentially serve as a
      therapeutic target in ADPKD.

PMID- 28747358
TI  - Urinary renin-angiotensin markers in polycystic kidney disease.
AB  - In autosomal dominant polycystic kidney disease (ADPKD), activation of the renin
      angiotensin aldosterone system (RAAS) may contribute to hypertension and disease
      progression. Although previous studies have focused on circulating RAAS
      components, preliminary evidence suggests that APDKD may increase urinary RAAS
      components. Therefore, our aim was to analyze circulating and urinary RAAS
      components in ADPKD. We cross-sectionally compared 60 patients with ADPKD with 57
      patients with non-ADPKD chronic kidney disease (CKD). The two groups were matched
      by sex, estimated glomerular filtration rate (eGFR), blood pressure, and RAAS
      inhibitor use. Despite similar plasma levels of angiotensinogen and renin,
      urinary angiotensinogen and renin excretion were five- to sixfold higher in ADPKD
      (P < 0.001). These differences persisted when adjusting for group differences and
      were present regardless of RAAS inhibitor use. In multivariable analyses, ADPKD,
      albuminuria, and the respective plasma concentrations were independent predictors
      for urinary angiotensinogen and renin excretion. In ADPKD, both plasma and
      urinary renin correlated negatively with eGFR. Total kidney volume correlated
      with plasma renin and albuminuria but not with urinary renin or angiotensinogen
      excretions. Albuminuria correlated positively with urinary angiotensinogen and
      renin excretions in ADPKD and CKD. In three ADPKD patients who underwent
      nephrectomy, the concentrations of albumin and angiotensinogen were highest in
      plasma, followed by cyst fluid and urine; urinary renin concentrations were
      higher than cyst fluid. In conclusion, this study shows that, despite similar
      circulating RAAS component levels, higher urinary excretions of angiotensinogen
      and renin are a unique feature of ADPKD. Future studies should address the
      underlying mechanism and whether this may contribute to hypertension or disease
      progression in ADPKD.

PMID- 28747359
TI  - Coupling between phosphate and calcium homeostasis: a mathematical model.
AB  - We developed a mathematical model of calcium (Ca) and phosphate (PO4) homeostasis
      in the rat to elucidate the hormonal mechanisms that underlie the regulation of
      Ca and PO4 balance. The model represents the exchanges of Ca and PO4 between the
      intestine, plasma, kidneys, bone, and the intracellular compartment, and the
      formation of Ca-PO4-fetuin-A complexes. It accounts for the regulation of these
      fluxes by parathyroid hormone (PTH), vitamin D3, fibroblast growth factor 23, and
      Ca2+-sensing receptors. Our results suggest that the Ca and PO4 homeostatic
      systems are robust enough to handle small perturbations in the production rate of
      either PTH or vitamin D3 The model predicts that large perturbations in PTH or
      vitamin D3 synthesis have a greater impact on the plasma concentration of Ca2+
      ([Ca2+]p) than on that of PO4 ([PO4]p); due to negative feedback loops, [PO4]p
      does not consistently increase when the production rate of PTH or vitamin D3 is
      decreased. Our results also suggest that, following a large PO4 infusion, the
      rapidly exchangeable pool in bone acts as a fast, transient storage PO4
      compartment (on the order of minutes), whereas the intracellular pool is able to
      store greater amounts of PO4 over several hours. Moreover, a large PO4 infusion
      rapidly lowers [Ca2+]p owing to the formation of CaPO4 complexes. A large Ca
      infusion, however, has a small impact on [PO4]p, since a significant fraction of
      Ca binds to albumin. This mathematical model is the first to include all major
      regulatory factors of Ca and PO4 homeostasis.

PMID- 28747361
TI  - Metabolic acidosis stimulates the production of the antimicrobial peptide
      cathelicidin in rabbit urine.
AB  - Intercalated cells of the collecting duct (CD) are critical for acid-base
      homeostasis and innate immune defense of the kidney. Little is known about the
      impact of acidosis on innate immune defense in the distal nephron. Urinary tract
      infections are mainly due to Escherichia coli and are an important risk factor
      for development of chronic kidney disease. While the effect of urinary pH on
      growth of E. coli is well established, in this study, we demonstrate that
      acidosis increases urine antimicrobial activity due, at least in part, to
      induction of cathelicidin expression within the CD. Acidosis was induced in
      rabbits by adding NH4Cl to the drinking water and reducing food intake over 3
      days or by casein supplementation. Microdissected CDs were examined for
      cathelicidin mRNA expression and antimicrobial activity, and cathelicidin protein
      levels in rabbit urine were measured. Cathelicidin expression in CD cells was
      detected in kidney sections. CDs from acidotic rabbits expressed three times more
      cathelicidin mRNA than those isolated from normal rabbits. Urine from acidotic
      rabbits had significantly more antimicrobial activity (vs. E. coli) than normal
      urine, and most of this increased activity was blocked by cathelicidin antibody.
      The antibody had little effect on antimicrobial activity of normal urine. Urine
      from acidotic rabbits had at least twice the amount of cathelicidin protein as
      did normal urine. We conclude that metabolic acidosis not only stimulates CD acid
      secretion but also induces expression of cathelicidin and, thereby, enhances
      innate immune defense against urinary tract infections via induction of
      antimicrobial peptide expression.

PMID- 28747360
TI  - Cannabinoids and the kidney: effects in health and disease.
AB  - Consumption of cannabis and various related products (cannabinoids) for both
      medicinal and recreational use is gaining popularity. Furthermore, regulatory
      changes are fostering a cultural shift toward increasing liberalization of
      cannabis use, thereby increasing the likelihood of even larger numbers of
      individuals being exposed in the future. The two different types of receptors
      (CB1 and CB2) that are activated by the pharmacologically active ingredients of
      cannabis are found in numerous tissues, including the kidneys. Experimental
      studies suggest that stimulation of these receptors using pharmacologic agents or
      their naturally occurring ligands could have both deleterious and beneficial
      effects on the kidneys, depending on receptor distribution, type of renal insult,
      or the timing of the activation during acute or chronic states of kidney injury.
      To date, the mechanisms by which the CB1 or CB2 receptors are involved in the
      pathology of these renal conditions remain to be fully described. Furthermore, a
      better understanding of the impact of exocannabinoids and endocannabinoids on the
      renal system may lead to the development of new drugs to treat kidney disease and
      its complications. Given the increasing public health relevance of cannabis
      exposure, it is clear that more research is necessary to clarify the various
      physiological and pathophysiological effects of cannabis and related analogs on
      the kidney. This will help limit the deleterious effects of these substances
      while promoting their potential beneficial impact on renal function in various
      types of kidney diseases.

PMID- 28747362
TI  - Alterations of adrenal steroidomic profiles in preterm infants at birth.
AB  - OBJECTIVE: Preterm infants have relative adrenal and kidney immaturity. Recently,
      we linked their urine sodium loss to a hypoaldosteronism at variance with an
      appropriate stimulation of the renin-angiotensin system. To investigate this
      defective aldosterone secretion, we analyse the biosynthesis pathways of adrenal
      steroids in neonates according to gestational age (GA). DESIGN: Multicentre study
      (Premaldo) including 152 neonates classified into three groups: group 1 (very
      preterm (VPT)): <33  gestational weeks (GW); group 2 (preterm (PT)): 33-36 GW and
      group 3 (term (T)): >=GW. METHOD: Steroidomic profiles of mineralocorticoids,
      glucocorticoids and adrenal androgens were established from umbilical cord at
      birth (n=152) and peripheral blood at day 3 (n=70) using a recently developed
      liquid chromatography mass spectrometry method (LC-MS/MS). The enzymatic activity
      of each biosynthesis step was estimated by the product-to-substrate ratio.
      RESULTS: At birth, VPT infants exhibit a global defect in adrenal steroid
      synthesis pathways leading to lower levels of aldosterone, cortisol and
      androstenedione than in term infants. This defect was strongly related to GA. On
      day 3, steroid precursors (progesterone, 11-deoxycorticosterone (DOC), 17
      hydroxyprogesterone(17-OH-P) and 11-deoxycortisol (S)) were higher in VPT and
      negatively correlated with GA. Despite of precursors' accumulation, aldosterone
      and cortisol were similar in the three groups. At birth and day 3, a low
      cortisol/11-deoxycortisol ratio was found in preterm infants, suggesting an 11
      beta-hydroxylase activity (CYP11B1) deficiency. CONCLUSIONS: At birth, VPT
      infants exhibit a global deficit in mineralocorticoids, glucocorticoids and
      adrenal androgens that attenuates on day 3 of life. Steroid profiling using LC
      MS/MS provides evidence for a partial defect in 11-hydroxylase along with
      prematurity.

PMID- 28747363
TI  - Changes in cardiac output and cerebral oxygenation during prone and supine sleep
      positioning in healthy term infants.
AB  - OBJECTIVE: To investigate the changes in systemic and cerebral haemodynamics
      between supine and prone sleep in healthy term infants during the early postnatal
      period. DESIGN/METHODS: Healthy term infants without congenital anomalies, patent
      ductus arteriosus and/or small for gestational age status were enrolled. Infants
      were placed in supine (SP1), prone (PP) and back in supine (SP2) position for 15
      min each while asleep. Cardiac output (CO) and stroke volume (SV) were assessed
      by electrical velocimetry (EV) and echocardiography (echo), and cerebral regional
      oxygen saturation (CrSO2) in the frontal lobes was monitored by near-infrared
      spectroscopy. Heart rate (HR) and SpO2 were continuously monitored by
      conventional monitoring. RESULTS: In 34 healthy term infants (mean age 3.7+/-1.2
      days; 16 females), 66 sets of serial CO measurements (34 EV and 32 echo) in three
      sleep positions were obtained. Mean COEV and COecho were 182+/-57 (SP1), 170+/-50
      (PP) and 177+/-54 (SP2), and 193+/-48 (SP1), 174+/-40 (PP) and 192+/-50 (SP2)
      mL/kg/min, respectively. Mean SVEV and SVecho were 1.46+/-0.47 (SP1), 1.36+/-0.38
      (PP) and 1.37+/-0.39 (SP2), and 1.54+/-40 (SP1), 1.38+/-0.38 (PP) and 1.51+/-0.41
      (SP2) mL/kg, respectively. Repeated measures analysis of variance revealed a
      decrease in CO and SV during prone positions by both EV and echo, while HR, SpO2
      and CrSO2 did not change. Thirty-eight per cent of the CO measurements
      decreased>=10% during prone positioning. CONCLUSIONS: In healthy term infants, CO
      decreases in prone position due to a decrease in SV and not HR. CO recovers when
      placed back in supine. However, frontal lobe CrSO2 does not change in the
      different positions.

PMID- 28747364
TI  - Cerebral oxygenation during skin-to-skin care in preterm infants not receiving
      respiratory support.
AB  - OBJECTIVE: Skin-to-skin care (SSC) has proven benefits in preterm infants, but
      increased hypoxic and bradycardic events have been reported. This may make
      clinicians hesitant to recommend SSC as standard care. We hypothesised that
      regional cerebral oxygenation (rStO2) measured with near infrared spectroscopy is
      not worse during SSC compared with standard incubator care. DESIGN: Prospective,
      observational, non-inferiority study. SETTING: Single tertiary perinatal centre
      in Australia. PATIENTS: Forty preterm infants (median (IQR) 30.6 (29.1-31.7)
      weeks' gestation) not receiving respiratory support were studied on day 14 (8
      38). INTERVENTIONS: Recordings during 90 min of incubator care, followed by 90
      min of SSC. Each infant acted as their own control and caregivers were blinded to
      the rStO2 measurements. MAIN OUTCOME MEASURES: The primary outcome was the mean
      difference in rStO2 between SSC and incubator care. The prespecified margin of
      non-inferiority was -1.5%. Secondary outcomes included heart rate (HR),
      peripheral oxygen saturation (SpO2), time in quiet sleep, temperature and hypoxic
      (SpO2 <80% for >5 s) or bradycardic events (HR <80 bpm for >5 s) and time spent
      in cerebral hypoxia (rStO2<55%) and hyperoxia (rStO2>85%). RESULTS: Mean (SD)
      rStO2 was lower during SSC compared with incubator care: 73.6 (6.0)% vs 74.8
      (4.6)%, mean difference (95% CI) 1.3 (2.2 to 0.4)%. HR was 5 bpm higher, SpO2 1%
      lower and time in quiet sleep 24% longer during SSC. Little evidence of a
      difference was observed in temperature. The number of hypoxic or bradycardic
      events as well as the proportion of time spent in cerebral hypoxia and hyperoxia
      was very low in both periods. CONCLUSIONS: Mean rStO2 was marginally lower during
      SSC without observed differences in hypoxic or bardycardic events but an increase
      in time spent in quiet sleep. TRIAL REGISTRATION NUMBER: This trial is linked to
      Australian New Zealand Clinical Trials Registry: identifier 12616000240448. It
      was registered pre-results.

PMID- 28747365
TI  - The antibiotic course has had its day.

PMID- 28747366
TI  - Cross-Reacting Ustilago maydis Causing False-Positive Cryptococcal Antigen Test
      Results.

PMID- 28747367
TI  - Rapid Detection of Bacillus anthracis Bloodstream Infections by Use of a Novel
      Assay in the GeneXpert System.
AB  - Bacillus anthracis is a tier 1 select agent with the potential to quickly cause
      severe disease. Rapid identification of this pathogen may accelerate treatment
      and reduce mortality in the event of a bioterrorism attack. We developed a rapid
      and sensitive assay to detect B. anthracis bacteremia using a system that is
      suitable for point-of-care testing. A filter-based cartridge that included both
      sample processing and PCR amplification functions was loaded with all reagents
      needed for sample processing and multiplex nested PCR. The assay limit of
      detection (LOD) and dynamic range were determined by spiking B. anthracis DNA
      into individual PCR mixtures and B. anthracis CFU into human blood. One
      milliliter blood samples were added to the filter-based detection cartridge and
      tested for B. anthracis on a GeneXpert instrument. Assay specificity was
      determined by testing blood spiked with non-anthrax bacterial isolates or by
      testing blood samples drawn from patients with concurrent non-B. anthracis
      bacteremia or nonbacteremic controls. The assay LODs were 5 genome equivalents
      per reaction and 10 CFU/ml blood for both the B. anthracis Sterne and V1B
      strains. There was a 6-log10 dynamic range. Assay specificity was 100% for tests
      of non-B. anthracis bacterial isolates and patient blood samples. Assay time was
      less than 90 min. This automated system suitable for point-of-care detection
      rapidly identifies B. anthracis directly from blood with high sensitivity. This
      assay might lead to early detection and more rapid therapy in the event of a
      bioterrorism attack.

PMID- 28747368
TI  - Fusarium Keratitis in Germany.
AB  - Fusarium keratitis is a destructive eye infection that is difficult to treat and
      results in poor outcome. In tropical and subtropical areas, the infection is
      relatively common and associated with trauma or chronic eye diseases. However, in
      recent years, an increased incidence has been reported in temperate climate
      regions. At the German National Reference Center, we have observed a steady
      increase in case numbers since 2014. Here, we present the first German case
      series of eye infections with Fusarium species. We identified Fusarium isolates
      from the eye or eye-related material from 22 patients in 2014 and 2015. Thirteen
      isolates belonged to the Fusarium solani species complex (FSSC), 6 isolates
      belonged to the Fusarium oxysporum species complex (FOSC), and three isolates
      belonged to the Fusarium fujikuroi species complex (FFSC). FSSC was isolated in
      13 of 15 (85%) definite infections and FOSC in 3 of 4 (75%) definite
      contaminations. Furthermore, diagnosis from contact lens swabs or a culture of
      contact lens solution turned out to be highly unreliable. FSSC isolates differed
      from FOSC and FFSC by a distinctly higher MIC for terbinafine. Outcome was often
      adverse, with 10 patients requiring keratoplasty or enucleation. The use of
      natamycin as the most effective agent against keratitis caused by filamentous
      fungi was rare in Germany, possibly due to restricted availability. Keratitis
      caused by Fusarium spp. (usually FSSC) appears to be a relevant clinical problem
      in Germany, with the use of contact lenses as the predominant risk factor. Its
      outcome is often adverse.

PMID- 28747369
TI  - Serum Hepatitis B Virus DNA, RNA, and HBsAg: Which Correlated Better with
      Intrahepatic Covalently Closed Circular DNA before and after Nucleos(t)ide
      Analogue Treatment?
AB  - The study was designed to investigate whether serum hepatitis B virus (HBV) RNA
      is a strong surrogate marker for intrahepatic HBV covalently closed circular DNA
      (cccDNA) compared with serum HBV DNA, hepatitis B surface antigen (HBsAg), and
      hepatitis B e antigen (HBeAg) in HBeAg-positive chronic hepatitis B (CHB)
      patients. Serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA were
      quantitatively detected at baseline (n = 82) and 96 weeks (n = 62) after
      treatment with nucleos(t)ide analogue (NUC) in HBeAg-positive CHB patients. The
      correlations among serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA
      levels were then statistically analyzed. The results showed that pretreatment
      intrahepatic cccDNA levels correlated better with serum HBV DNA levels (r = 0.36,
      P < 0.01) than with serum HBV RNA levels (r = 0.25, P = 0.02), whereas no
      correlations were found between pretreatment intrahepatic cccDNA levels and HBsAg
      (r = 0.15, P = 0.17) or HBeAg (r = 0.07, P = 0.56) levels. At 96 weeks after NUC
      treatment, intrahepatic cccDNA levels correlated well with HBsAg levels (r =
      0.39, P < 0.01) but not with serum HBV RNA, HBV DNA, and HBeAg levels (all P >
      0.05). Besides, the decline in the intrahepatic cccDNA level from baseline to
      week 96 correlated better with the reduction in the serum HBsAg levels than with
      the decreases in the levels of the other markers (for the HBsAg decline, r =
      0.38, P < 0.01; for the HBV DNA decline, r = 0.35, P = 0.01; for the HBV RNA
      decline, r = 0.28, P < 0.05; for the HBeAg decline, r = 0.18, P = 0.19). In
      conclusion, the baseline serum HBV RNA level or its decline after 96 weeks of NUC
      therapy correlated with the corresponding intrahepatic cccDNA level, while it was
      less than that seen with serum HBV DNA at baseline and HBsAg (or its decline) at
      96 weeks after treatment, respectively.

PMID- 28747370
TI  - Survival, Persistence, and Isolation of the Emerging Multidrug-Resistant
      Pathogenic Yeast Candida auris on a Plastic Health Care Surface.
AB  - The emerging multidrug-resistant pathogenic yeast Candida auris represents a
      serious threat to global health. Unlike most other Candida species, this organism
      appears to be commonly transmitted within health care facilities and causes
      health care-associated outbreaks. To better understand the epidemiology of this
      emerging pathogen, we investigated the ability of C. auris to persist on plastic
      surfaces common in health care settings compared with that of Candida
      parapsilosis, a species known to colonize the skin and plastics. Specifically, we
      compiled comparative and quantitative data essential to understanding the
      vehicles of spread and the ability of both species to survive and persist on
      plastic surfaces under controlled conditions (25 degrees C and 57% relative
      humidity), such as those found in health care settings. When a test suspension of
      104 cells was applied and dried on plastic surfaces, C. auris remained viable for
      at least 14 days and C. parapsilosis for at least 28 days, as measured by CFU.
      However, survival measured by esterase activity was higher for C. auris than C.
      parapsilosis throughout the 28-day study. Given the notable length of time
      Candida species survive and persist outside their host, we developed methods to
      more effectively culture C. auris from patients and their environment. Using our
      enrichment protocol, public health laboratories and researchers can now readily
      isolate C. auris from complex microbial communities (such as patient skin,
      nasopharynx, and stool) as well as environmental biofilms, in order to better
      understand and prevent C. auris colonization and transmission.

PMID- 28747371
TI  - Designing HIV Testing Algorithms Based on 2015 WHO Guidelines Using Data from Six
      Sites in Sub-Saharan Africa.
AB  - Our objective was to evaluate the performance of HIV testing algorithms based on
      WHO recommendations, using data from specimens collected at six HIV testing and
      counseling sites in sub-Saharan Africa (Conakry, Guinea; Kitgum and Arua, Uganda;
      Homa Bay, Kenya; Douala, Cameroon; Baraka, Democratic Republic of Congo). A total
      of 2,780 samples, including 1,306 HIV-positive samples, were included in the
      analysis. HIV testing algorithms were designed using Determine as a first test.
      Second and third rapid diagnostic tests (RDTs) were selected based on site
      specific performance, adhering where possible to the WHO-recommended minimum
      requirements of >=99% sensitivity and specificity. The threshold for specificity
      was reduced to 98% or 96% if necessary. We also simulated algorithms consisting
      of one RDT followed by a simple confirmatory assay. The positive predictive
      values (PPV) of the simulated algorithms ranged from 75.8% to 100% using
      strategies recommended for high-prevalence settings, 98.7% to 100% using
      strategies recommended for low-prevalence settings, and 98.1% to 100% using a
      rapid test followed by a simple confirmatory assay. Although we were able to
      design algorithms that met the recommended PPV of >=99% in five of six sites
      using the applicable high-prevalence strategy, options were often very limited
      due to suboptimal performance of individual RDTs and to shared falsely reactive
      results. These results underscore the impact of the sequence of HIV tests and of
      shared false-reactivity data on algorithm performance. Where it is not possible
      to identify tests that meet WHO-recommended specifications, the low-prevalence
      strategy may be more suitable.

PMID- 28747372
TI  - Determination of Disk Diffusion and MIC Quality Control Ranges for Nafithromycin
      (WCK 4873), a New Lactone-Ketolide.
AB  - Disk diffusion and MIC quality control (QC) ranges were determined for
      nafithromycin, a new lactone-ketolide, following the completion of a nine
      laboratory, Clinical and Laboratory Standards Institute (CLSI) document M23
      defined tier 2 study. Five QC strains consistent with the spectrum of activity of
      nafithromycin were tested: Staphylococcus aureus ATCC 25923 (disk only), S.
      aureus ATCC 29213 (broth only), Enterococcus faecalis ATCC 29212 (broth only),
      Streptococcus pneumoniae ATCC 49619 (disk and broth), and Haemophilus influenzae
      ATCC 49247 (disk and broth). Nafithromycin disk diffusion QC ranges were
      determined to be 25 to 31 mm for S. aureus ATCC 25923, 25 to 31 mm for S.
      pneumoniae ATCC 49619, and 16 to 20 mm for H. influenzae ATCC 49247.
      Nafithromycin MIC QC ranges were determined to be 0.06 to 0.25 MUg/ml for S.
      aureus ATCC 29213, 0.016 to 0.12 MUg/ml for E. faecalis ATCC 29212, 0.008 to 0.03
      MUg/ml for S. pneumoniae ATCC 49619, and 2 to 8 MUg/ml for H. influenzae ATCC
      49247. All disk diffusion and MIC QC ranges established in this study were
      approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing at
      their June 2015 meeting and were initially reported in the 2017 M100S document.
      The QC ranges established in this study should be used for determining the in
      vitro activity of nafithromycin in phase 2 and phase 3 human clinical trials and
      subsequently for testing patient isolates and isolates in phase 4 surveillance
      studies.

PMID- 28747373
TI  - Investigation of Respiratory Syncytial Virus Outbreak on an Adult Stem Cell
      Transplant Unit by Use of Whole-Genome Sequencing.
AB  - A viral whole-genome sequencing (WGS) strategy, based on PCR amplification
      followed by next-generation sequencing, was used to investigate a nosocomial
      respiratory syncytial virus-B (RSV-B) outbreak in a hematology-oncology and stem
      cell transplant unit. RSV-B genomes from 16 patients and health care workers
      (HCWs) suspected to be involved in the outbreak were compared to RSV-B genomes
      that were acquired from outpatients during the same time period but
      epidemiologically unrelated to the outbreak. Phylogenetic analysis of the whole
      genome identified a cluster of 11 patients and HCWs who had an identical RSV-B
      strain which was clearly distinct from strains recovered from individuals
      unrelated to the outbreak. Sequence variation of the glycoprotein (G) gene alone
      was insufficient to distinguish the outbreak strains from the outbreak-unrelated
      strains, thereby demonstrating that WGS is valuable for local outbreak
      investigation.

PMID- 28747374
TI  - Babesia microti: from Mice to Ticks to an Increasing Number of Highly Susceptible
      Humans.
AB  - Babesia microti, a zoonotic intraerythrocytic parasite, is the primary
      etiological agent of human babesiosis in the United States. Human infections
      range from subclinical illness to severe disease resulting in death, with
      symptoms being related to host immune status. Despite advances in our
      understanding and management of B. microti, the incidence of infection in the
      United States has increased. Therefore, research focused on eradicating disease
      and optimizing clinical management is essential. Here we review this remarkable
      organism, with emphasis on the clinical, diagnostic, and therapeutic aspects of
      human disease.

PMID- 28747375
TI  - Evaluation of the Rapid Polymyxin NP Test for Polymyxin B Resistance Detection
      Using Enterobacter cloacae and Enterobacter aerogenes Isolates.
AB  - Polymyxin resistance is an increasing problem worldwide. Currently, determining
      susceptibility to polymyxins is problematic and lengthy. Polymyxins diffuse
      poorly into agar, potentially giving inaccurate disk diffusion and Etest results.
      A rapid screening test (2 h) for the detection of polymyxin resistance in
      Enterobacteriaceae, developed by P. Nordmann and L. Poirel (rapid polymyxin NP
      test) in 2016, detects glucose metabolization in the presence of polymyxin E (PE)
      and PB via pH-induced color change. The sensitivity and specificity were 99.3 and
      95.4%, respectively, with results obtained in <=2 h. Our goal was to evaluate
      this test using PB against larger numbers of Enterobacter A total of 143
      nonduplicate Enterobacter isolates (102 E. cloacae complex, 41 E. aerogenes) were
      tested, including 136 collected from Ochsner Health System patients from March to
      May 2016 and 7 previously determined PB-resistant E. cloacae isolates from JMI
      Laboratories. MICs were determined via broth microdilution. For the rapid
      polymyxin NP test, a color change from orange to yellow is positive; a weak/no
      color change is deemed negative after 4 h. Of 143 Enterobacter isolates, 25 were
      determined to be PB resistant by broth microdilution (MIC > 2 MUg/ml), including
      all 7 JMI isolates. Of these 25, 7 were positive by the rapid polymyxin NP test
      (included 3/7 JMI isolates). All 118 isolates determined to be PB susceptible by
      broth microdilution were NP test negative. The sensitivity and specificity for
      the rapid polymyxin NP test were 25 and 100%, respectively, compared to broth
      microdilution. Although the rapid polymyxin NP test is a much faster method (2 to
      4 h) for polymyxin resistance determination compared to broth microdilution (16
      to 20 h), our study indicates that it may be subject to limitations when testing
      Enterobacter.

PMID- 28747376
TI  - Long-term adverse effects of intramuscular oil injection.

PMID- 28747377
TI  - Erratum. Loss of Mbd2 Protects Mice Against High-Fat Diet-Induced Obesity and
      Insulin Resistance by Regulating the Homeostasis of Energy Storage and
      Expenditure. Diabetes 2016;65:3384-3395.

PMID- 28747378
TI  - NADPH Oxidase Nox5 Accelerates Renal Injury in Diabetic Nephropathy.
AB  - NADPH oxidase-derived excessive production of reactive oxygen species (ROS) in
      the kidney plays a key role in mediating renal injury in diabetes. Pathological
      changes in diabetes include mesangial expansion and accumulation of extracellular
      matrix (ECM) leading to glomerulosclerosis. There is a paucity of data about the
      role of the Nox5 isoform of NADPH oxidase in animal models of diabetic
      nephropathy since Nox5 is absent in the mouse genome. Thus, we examined the role
      of Nox5 in human diabetic nephropathy in human mesangial cells and in an
      inducible human Nox5 transgenic mouse exposed to streptozotocin-induced diabetes.
      In human kidney biopsies, Nox5 was identified to be expressed in glomeruli, which
      appeared to be increased in diabetes. Colocalization demonstrated Nox5 expression
      in mesangial cells. In vitro, silencing of Nox5 in human mesangial cells was
      associated with attenuation of the hyperglycemia and TGF-beta1-induced enhanced
      ROS production, increased expression of profibrotic and proinflammatory
      mediators, and increased TRPC6, PKC-alpha, and PKC-beta expression. In vivo,
      vascular smooth muscle cell/mesangial cell-specific overexpression of Nox5 in a
      mouse model of diabetic nephropathy showed enhanced glomerular ROS production,
      accelerated glomerulosclerosis, mesangial expansion, and ECM protein (collagen IV
      and fibronectin) accumulation as well as increased macrophage infiltration and
      expression of the proinflammatory chemokine MCP-1. Collectively, this study
      provides evidence of a role for Nox5 and its derived ROS in promoting progression
      of diabetic nephropathy.

PMID- 28747379
TI  - Advances in the diagnosis of pneumonia in children.
AB  - Pneumonia remains a major cause of childhood mortality and morbidity globally.
      Accurate diagnosis and attribution of the causes of pneumonia are important for
      measuring the burden of disease, implementing appropriate preventive or treatment
      strategies, and developing more effective interventions. This review summarizes
      recent diagnostic advances in radiological techniques, specimen collection, and
      laboratory methods. Although chest ultrasound and chest magnetic resonance
      imaging are promising modalities for radiological diagnosis, their role in
      clinical management and their impact on outcomes need further study. Rapid,
      highly sensitive, multiplex laboratory tests performed on upper respiratory tract
      samples or induced sputum can detect nucleic acid from potential pathogens in
      most children with pneumonia. However, it may be difficult to attribute causality
      because it is often impossible to distinguish between organisms colonizing or
      infecting the upper respiratory tract and those causing pneumonia. Currently
      available host biomarkers lack accuracy for distinguishing bacterial or mixed
      bacterial-viral infections from viral infections. New biomarkers derived from
      host transcriptional profile analysis may be more accurate but require
      validation. Prospective studies with appropriate control populations, including
      studies of clinical impact, are needed to improve our understanding of the role
      of tests. Although progress has been made in radiological techniques and
      laboratory testing, current methods for diagnosing and attributing the causes of
      pneumonia are suboptimal.

PMID- 28747380
TI  - Identification of Differentially Expressed Splice Variants by the Proteogenomic
      Pipeline Splicify.
AB  - Proteogenomics, i.e. comprehensive integration of genomics and proteomics data,
      is a powerful approach identifying novel protein biomarkers. This is especially
      the case for proteins that differ structurally between disease and control
      conditions. As tumor development is associated with aberrant splicing, we focus
      on this rich source of cancer specific biomarkers. To this end, we developed a
      proteogenomic pipeline, Splicify, which can detect differentially expressed
      protein isoforms. Splicify is based on integrating RNA massive parallel
      sequencing data and tandem mass spectrometry proteomics data to identify protein
      isoforms resulting from differential splicing between two conditions. Proof of
      concept was obtained by applying Splicify to RNA sequencing and mass spectrometry
      data obtained from colorectal cancer cell line SW480, before and after siRNA
      mediated downmodulation of the splicing factors SF3B1 and SRSF1. These analyses
      revealed 2172 and 149 differentially expressed isoforms, respectively, with
      peptide confirmation upon knock-down of SF3B1 and SRSF1 compared with their
      controls. Splice variants identified included RAC1, OSBPL3, MKI67, and SYK. One
      additional sample was analyzed by PacBio Iso-Seq full-length transcript
      sequencing after SF3B1 downmodulation. This analysis verified the alternative
      splicing identified by Splicify and in addition identified novel splicing events
      that were not represented in the human reference genome annotation. Therefore,
      Splicify offers a validated proteogenomic data analysis pipeline for
      identification of disease specific protein biomarkers resulting from mRNA
      alternative splicing. Splicify is publicly available on GitHub
      (https://github.com/NKI-TGO/SPLICIFY) and suitable to address basic research
      questions using pre-clinical model systems as well as translational research
      questions using patient-derived samples, e.g. allowing to identify clinically
      relevant biomarkers.

PMID- 28747381
TI  - Rapid evolution of female-biased genes among four species of Anopheles malaria
      mosquitoes.
AB  - Understanding how phenotypic differences between males and females arise from the
      sex-biased expression of nearly identical genomes can reveal important insights
      into the biology and evolution of a species. Among Anopheles mosquito species,
      these phenotypic differences include vectorial capacity, as it is only females
      that blood feed and thus transmit human malaria. Here, we use RNA-seq data from
      multiple tissues of four vector species spanning the Anopheles phylogeny to
      explore the genomic and evolutionary properties of sex-biased genes. We find
      that, in these mosquitoes, in contrast to what has been found in many other
      organisms, female-biased genes are more rapidly evolving in sequence, expression,
      and genic turnover than male-biased genes. Our results suggest that this atypical
      pattern may be due to the combination of sex-specific life history challenges
      encountered by females, such as blood feeding. Furthermore, female propensity to
      mate only once in nature in male swarms likely diminishes sexual selection of
      post-reproductive traits related to sperm competition among males. We also
      develop a comparative framework to systematically explore tissue- and sex
      specific splicing to document its conservation throughout the genus and identify
      a set of candidate genes for future functional analyses of sex-specific isoform
      usage. Finally, our data reveal that the deficit of male-biased genes on the X
      Chromosomes in Anopheles is a conserved feature in this genus and can be directly
      attributed to chromosome-wide transcriptional regulation that de-masculinizes the
      X in male reproductive tissues.

PMID- 28747382
TI  - Just five words... 'How physically active are you?'

PMID- 28747384
TI  - Feeding Releases Endogenous Opioids in Humans.
AB  - The endogenous opioid system supports a multitude of functions related to
      appetitive behavior in humans and animals, and it has been proposed to govern
      hedonic aspects of feeding thus contributing to the development of obesity. Here
      we used positron emission tomography to investigate whether feeding results in
      hedonia-dependent endogenous opioid release in humans. Ten healthy males were
      recruited for the study. They were scanned with the MU-opioid-specific ligand
      [11C]carfentanil three times, as follows: after a palatable meal, a nonpalatable
      meal, and after an overnight fast. Subjective mood, satiety, and circulating
      hormone levels were measured. Feeding induced significant endogenous opioid
      release throughout the brain. This response was more pronounced following a
      nonpalatable meal versus a palatable meal, and independent of the subjective
      hedonic responses to feeding. We conclude that feeding consistently triggers
      cerebral opioid release even in the absence of subjective pleasure associated
      with feeding, suggesting that metabolic and homeostatic rather than exclusively
      hedonic responses play a role in the feeding-triggered cerebral opioid
      release.SIGNIFICANCE STATEMENT The endogenous opioid system supports both hedonic
      and homeostatic functions. It has been proposed that overeating and concomitant
      opioid release could downregulate opioid receptors and promote the development of
      obesity. However, it remains unresolved whether feeding leads to endogenous
      opioid release in humans. We used in vivo positron emission tomography to test
      whether feeding triggers cerebral opioid release and whether this response is
      associated with pleasurable sensations. We scanned volunteers using the MU-opioid
      receptor-specific radioligand [11C]carfentanil three times, as follows: after an
      overnight fast, after consuming a palatable meal, and after consuming a
      nonpalatable meal. Feeding led to significant endogenous opioid release, and this
      occurred also in the absence of feeding-triggered hedonia. Feeding-triggered
      opioid release thus also reflects metabolic and homeostatic responses rather than
      hedonic responses exclusively.

PMID- 28747385
TI  - Spinal RacGAP alpha-Chimaerin Is Required to Establish the Midline Barrier for
      Proper Corticospinal Axon Guidance.
AB  - In the developing CNS, the midline barrier, which comprises guidance molecule
      expressing midline glial somata and processes, plays a pivotal role in midline
      axon guidance. Accumulating evidence has revealed the molecular mechanisms by
      which the midline barrier ensures proper midline guidance for axons. In contrast,
      the mechanisms for establishing the midline barrier remain obscure. Here, we
      report that Rac-specific GTPase-activating protein (RacGAP) alpha-chimaerin is
      required for both axonal repulsion at and establishment of the midline barrier in
      the spinal cord. We generated cortex-specific and spinal-cord-specific alpha
      chimaerin gene (Chn1) knock-out mice (Cx-Chn1KO and Sp-Chn1KO mice, respectively)
      and found that both showed aberrant corticospinal tract (CST) axon midline
      crossing in the spinal cord. Strikingly, Sp-Chn1KO mice had breaks (holes) in the
      ephrinB3(+) spinal midline barrier and EphA4(+) CST axons aberrantly crossed the
      midline through these holes. During normal embryonic development, EphA4(+) spinal
      cells are located in juxta-midline areas but are excluded from the midline. In
      contrast, in Chn1KO embryos, several EphA4(+) cells were aberrantly relocated
      into the midline and the midline barrier was broken around these cells.
      Similarly, the spinal cord midline of Epha4KO mice was invaded by juxta-midline
      EphA4 cells (i.e., Epha4 promoter-active cells) during the embryonic stage and
      holes were formed in the midline barrier. Juxta-midline EphA4 cells in the spinal
      cord expressed alpha-chimaerin. We propose that spinal alpha-chimaerin aids in
      establishing an intact spinal midline barrier by mediating juxta-midline EphA4(+)
      cell repulsion, thus preventing these cells from breaking into the ephrinB3(+)
      midline barrier.SIGNIFICANCE STATEMENT The midline barrier plays a critical role
      in midline axon guidance, which is fundamental to the formation of neural
      circuits that are responsible for proper left-right coordination of the body.
      Studies have revealed some of the mechanisms underlying how the midline barrier
      navigates axons. In contrast, the establishment of the midline barrier during
      embryonic development remains unclear. In this study, we determined that alpha
      chimaerin is required for the formation of an intact midline barrier. Spinal-cord
      specific alpha-chimaerin knock-out mice had spinal midline barriers with numerous
      breaks (holes), through which corticospinal axons aberrantly crossed the midline.
      We propose that alpha-chimaerin protects the midline barrier by mediating cell
      repulsive signaling in juxta-midline cells, which prevents these cells from
      invading the midline.

PMID- 28747383
TI  - Ischemia/Reperfusion Induces Interferon-Stimulated Gene Expression in Microglia.
AB  - Innate immune signaling is important in the pathophysiology of
      ischemia/reperfusion (stroke)-induced injury and recovery. Several lines of
      evidence support a central role for microglia in these processes. Recent work has
      identified Toll-like receptors (TLRs) and type I interferon (IFN) signaling in
      both ischemia/reperfusion-induced brain injury and ischemic preconditioning
      mediated neuroprotection. To determine the effects of "ischemia/reperfusion-like"
      conditions on microglia, we performed genomic analyses on wild-type (WT) and TLR4
      /- cultured microglia after sequential exposure to hypoxia/hypoglycemia and
      normoxia/normoglycemia (H/H-N/N). We observed increased expression of type 1 IFN
      stimulated genes (ISGs) as the predominant transcriptomal feature of H/H-N/N
      exposed WT, but not TLR4-/-, microglia. Microarray analysis on ex vivo sorted
      microglia from ipsilateral male mouse cortex after a transient in vivo ischemic
      pulse also demonstrated robust expression of ISGs. Type 1 IFNs, including the IFN
      alphas and IFN-beta, activate the interferon-alpha/beta receptor (IFNAR) complex.
      We confirmed both in vitro H/H-N/N- and in vivo ischemia/reperfusion-induced
      microglial ISG responses by quantitative real-time PCR and demonstrated that both
      were dependent on IFNAR1. We characterized the effects of hypoxia/hypoglycemia on
      phosphorylation of signal transducer and activator of transcription 1 (STAT1),
      release of type 1 IFNs, and surface expression of IFNAR1 in microglia. We
      demonstrated that IFN-beta induces dose-dependent secretion of ISG chemokines in
      cultured microglia and robust ISG expression in microglia both in vitro and in
      vivo Finally, we demonstrated that the microglial ISG chemokine responses to TLR4
      agonists were dependent on TLR4 and IFNAR1. Together, these data suggest novel
      ischemia/reperfusion-induced pathways for both TLR4-dependent and -independent,
      IFNAR1-dependent, type 1 IFN signaling in microglia.SIGNIFICANCE STATEMENT Stroke
      is the fifth leading cause of death in the United States and is a leading cause
      of serious long-term disability worldwide. Innate immune responses are critical
      in stroke pathophysiology, and microglia are key cellular effectors in the CNS
      response to ischemia/reperfusion. Using a transcriptional analysis approach, we
      identified a robust interferon (IFN)-stimulated gene response within microglia
      exposed to ischemia/reperfusion in both in vitro and in vivo experimental
      paradigms. Using a number of complementary techniques, we have demonstrated that
      these responses are dependent on innate immune signaling components including
      Toll-like receptor-4 and type I IFNs. We have also elucidated several novel
      ischemia/reperfusion-induced microglial signaling mechanisms.

PMID- 28747386
TI  - The association of autoimmune thyroid disease (AITD) with psoriatic disease: a
      prospective cohort study, systematic review and meta-analysis.
AB  - OBJECTIVE: Autoimmune thyroid disease (AITD) and psoriatic disease share auto
      immunological components. Few studies have investigated the link between both,
      yielding inconclusive results. DESIGN: We assessed the association of AITD with
      psoriatic disease in a prospective cohort study and performed a systematic review
      and meta-analysis. METHODS: 8214 participants of the Rotterdam Study (RS) with
      thyroid peroxidase antibodies (TPO-Abs), thyroid-stimulating hormone (TSH) and/or
      free thyroxine (FT4) measurements and information on psoriatic disease were
      included. We performed logistic and Cox regression analyses and a systematic
      literature search in several electronic databases on AITD and psoriatic disease.
      We pooled odds ratios (ORs) of included studies using the Mantel-Haenszel method,
      while adding RS data on prevalent psoriatic disease. RESULTS: Within the RS, we
      found no association between TPO-Ab positivity and psoriatic disease. There was a
      positive trend between TSH and prevalent psoriatic disease, and between FT4 and
      incident psoriatic disease, although not significant. Out of 1850 articles
      identified, seven were included in the systematic review and four in the meta
      analysis. The risk of psoriatic disease (pooled OR) was 1.71 (confidence interval
      (CI): 1.27-2.31) for TPO-Ab positivity, 1.25 (CI: 1.14-1.37) for AITD and 1.34
      (CI: 1.16-1.54) respectively, and 1.17 (CI: 1.03-1.32) for hypothyroidism and
      hyperthyroidism. CONCLUSIONS: Our meta-analysis suggests that TPO-Ab positivity,
      hypothyroidism and hyperthyroidism might be associated with prevalent psoriatic
      disease. However, there are only few studies with large heterogeneity regarding
      psoriatic disease definition and indication of publication bias. Additional
      prospective data are needed to assess the association of AITD with incident
      psoriatic disease.

PMID- 28747387
TI  - Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas.
AB  - The pathophysiology of aldosterone-producing adenomas (APAs) has been
      investigated via genetic approaches and the pathogenic significance of a series
      of somatic mutations, including KCNJ5, has been uncovered. However, how the
      mutational status of an APA is associated with its molecular characteristics,
      including its transcriptome and methylome, has not been fully understood. This
      study was undertaken to explore the molecular characteristics of APAs,
      specifically focusing on APAs with KCNJ5 mutations as opposed to those without
      KCNJ5 mutations, by comparing their transcriptome and methylome status. Cortisol
      producing adenomas (CPAs) were used as reference. We conducted transcriptome and
      methylome analyses of 29 APAs with KCNJ5 mutations, 8 APAs without KCNJ5
      mutations and 5 CPAs. Genome-wide gene expression and CpG methylation profiles
      were obtained from RNA and DNA samples extracted from these 42 adrenal tumors.
      Cluster analysis of the transcriptome and methylome revealed molecular
      heterogeneity in APAs depending on their mutational status. DNA hypomethylation
      and gene expression changes in Wnt signaling and inflammatory response pathways
      were characteristic of APAs with KCNJ5 mutations. Comparisons between
      transcriptome data from our APAs and that from normal adrenal cortex obtained
      from the Gene Expression Omnibus suggested similarities between APAs with KCNJ5
      mutations and zona glomerulosa. The present study, which is based on
      transcriptome and methylome analyses, indicates the molecular heterogeneity of
      APAs depends on their mutational status. Here, we report the unique
      characteristics of APAs with KCNJ5 mutations.

PMID- 28747388
TI  - Neuronal P2X7 Receptors Revisited: Do They Really Exist?
AB  - P2X7 receptors (Rs) constitute a subclass of ATP-sensitive ionotropic receptors
      (P2X1-P2X7). P2X7Rs have many distinguishing features, mostly based on their long
      intracellular C terminus regulating trafficking to the cell membrane, protein
      protein interactions, and post-translational modification. Their C-terminal tail
      is especially important in enabling the transition from the nonselective ion
      channel mode to a membrane pore allowing the passage of large molecules. There is
      an ongoing dispute on the existence of neuronal P2X7Rs with consequences for our
      knowledge on their involvement in neuroinflammation, aggravating stroke, temporal
      lobe epilepsy, neuropathic pain, and various neurodegenerative diseases. Whereas
      early results appeared to support the operation of P2X7Rs at neurons, more
      recently glial P2X7Rs are increasingly considered as indirect causes of neuronal
      effects. Specific tools for P2X7Rs are of limited value because of the poor
      selectivity of agonists, and the inherent failure of antibodies to differentiate
      between the large number of active and inactive splice variants, or gain-of
      function and loss-of-function small nucleotide polymorphisms of the receptor.
      Unfortunately, the available P2RX7 knock-out mice generated by pharmaceutical
      companies possess certain splice variants, which evade inactivation. In view of
      the recently discovered bidirectional dialogue between astrocytes and neurons
      (and even microglia and neurons), we offer an alternative explanation for
      previous data, which assumedly support the existence of P2X7Rs at neurons. We
      think that the unbiased reader will follow our argumentation on astrocytic or
      microglial P2X7Rs being the primary targets of pathologically high extracellular
      ATP concentrations, although a neuronal localization of these receptors cannot be
      fully excluded either.

PMID- 28747390
TI  - beta-Catenin Pathway Is Involved in TREM2-Mediated Microglial Survival.

PMID- 28747389
TI  - Neuronal P2X7 Receptor: Involvement in Neuronal Physiology and Pathology.
AB  - The proposed presence of P2X7 receptor (P2X7R) in neurons has been the source of
      some contention. Initial studies suggested an absence of P2X7R mRNA in neurons,
      and the apparent nonspecificity of the antibodies used to identify P2X7R raised
      further doubts. However, subsequent studies using new pharmacological and
      biomolecular tools provided conclusive evidence supporting the existence of
      functional P2X7Rs in neurons. The P2X7 receptor has since been shown to play a
      leading role in multiple aspects of neuronal physiology, including axonal
      elongation and branching and neurotransmitter release. P2X7R has also been
      implicated in neuronal pathologies, in which it may influence neuronal survival.
      Together, this body of research suggests that P2X7R may constitute an important
      therapeutic target for a variety of neurological disorders.

PMID- 28747391
TI  - Respiration: A New Mechanism for CSF Circulation?

PMID- 28747392
TI  - Evaluation of grading systems in stage I lung adenocarcinomas: a retrospective
      cohort study.
AB  - AIMS: There is no internationally accepted grading system for lung adenocarcinoma
      despite the new WHO classification. The architectural grade, the Kadota grade and
      the Sica score were evaluated and compared with overall (OS) and disease-free
      survival (DFS). METHODS: Comprehensive histological subtyping was used in a
      series of resected stage I lung adenocarcinoma to identify subtypes of
      adenocarcinomas, the architectural grade, the Kadota grade, the Sica grade, the
      mitotic count, nuclear atypia, the presence of lymphovascular, vascular and
      airway propagation, necrosis, and micropapillary or solid growth pattern in any
      percentage. Statistical models fitted included Kaplan-Meier estimates and Cox
      proportional hazard regression models. RESULTS: 261 stage I adenocarcinomas were
      included. The 5-year survivals of different subtypes were as follows: lepidic
      (n=40, OS: 92.5%; DFS 91.6%), acinar (n=54, OS: 81.8%; DFS: 68.6%), papillary
      (n=49, OS: 73.6%; DFS: 61.0%), solid (n=95, OS: 64.7%; DFS: 57.8%) and
      micropapillary (n=23, OS: 34.8%; DFS: 33.5%). Concerning the architectural grade,
      there were significant differences between OS and DFS of low and intermediate
      (pOS=0.005, pDFS<0.001), low and high (pOS<0.001, pDFS<0.001) and intermediate
      and high grades (pOS=0.002, pDFS<0.001). Low-grade and intermediate grade tumours
      did not differ in survival according to Kadota grade and Sica grade. In the
      multivariable model, architectural grade was found to be an independent
      prognostic marker. In another model, architectural pattern proved to be superior
      to architectural grade. CONCLUSIONS: Of the three grading systems compared, the
      architectural grade makes the best distinction between the outcome of low-grade,
      intermediate-grade and high-grade stage I adenocarcinomas.

PMID- 28747393
TI  - Improving validation methods for molecular diagnostics: application of Bland
      Altman, Deming and simple linear regression analyses in assay comparison and
      evaluation for next-generation sequencing.
AB  - AIMS: A standard approach in test evaluation is to compare results of the assay
      in validation to results from previously validated methods. For quantitative
      molecular diagnostic assays, comparison of test values is often performed using
      simple linear regression and the coefficient of determination (R2), using R2 as
      the primary metric of assay agreement. However, the use of R2 alone does not
      adequately quantify constant or proportional errors required for optimal test
      evaluation. More extensive statistical approaches, such as Bland-Altman and
      expanded interpretation of linear regression methods, can be used to more
      thoroughly compare data from quantitative molecular assays. METHODS: We present
      the application of Bland-Altman and linear regression statistical methods to
      evaluate quantitative outputs from next-generation sequencing assays (NGS). NGS
      derived data sets from assay validation experiments were used to demonstrate the
      utility of the statistical methods. RESULTS: Both Bland-Altman and linear
      regression were able to detect the presence and magnitude of constant and
      proportional error in quantitative values of NGS data. Deming linear regression
      was used in the context of assay comparison studies, while simple linear
      regression was used to analyse serial dilution data. Bland-Altman statistical
      approach was also adapted to quantify assay accuracy, including constant and
      proportional errors, and precision where theoretical and empirical values were
      known. CONCLUSIONS: The complementary application of the statistical methods
      described in this manuscript enables more extensive evaluation of performance
      characteristics of quantitative molecular assays, prior to implementation in the
      clinical molecular laboratory.

PMID- 28747394
TI  - Asymmetric drop coalescence launches fungal ballistospores with directionality.
AB  - Thousands of fungal species use surface energy to power the launch of their
      ballistospores. The surface energy is released when a spherical Buller's drop at
      the spore's hilar appendix merges with a flattened drop on the adaxial side of
      the spore. The launching mechanism is primarily understood in terms of energetic
      models, and crucial features such as launching directionality are unexplained.
      Integrating experiments and simulations, we advance a mechanistic model based on
      the capillary-inertial coalescence between the Buller's drop and the adaxial
      drop, a pair that is asymmetric in size, shape and relative position. The
      asymmetric coalescence is surprisingly effective and robust, producing a
      launching momentum governed by the Buller's drop and a launching direction along
      the adaxial plane of the spore. These key functions of momentum generation and
      directional control are elucidated by numerical simulations, demonstrated on
      spore-mimicking particles, and corroborated by published ballistospore
      kinematics. Our work places the morphological and kinematic diversity of
      ballistospores into a general mechanical framework, and points to a generic
      catapulting mechanism of colloidal particles with implications for both biology
      and engineering.

PMID- 28747395
TI  - The role of the leading edge vortex in lift augmentation of steadily revolving
      wings: a change in perspective.
AB  - The presence of a stable leading edge vortex (LEV) on steadily revolving wings
      increases the maximum lift coefficient that can be generated from the wing and
      its role is important to understanding natural flyers and flapping wing vehicles.
      In this paper, the role of LEV in lift augmentation is discussed under two
      hypotheses referred to as 'additional lift' and 'absence of stall'. The
      'additional lift' hypothesis represents the traditional view. It presumes that an
      additional suction/circulation from the LEV increases the lift above that of a
      potential flow solution. This behaviour may be represented through either the
      'Polhamus leading edge suction' model or the so-called 'trapped vortex' model.
      The 'absence of stall' hypothesis is a more recent contender that presumes that
      the LEV prevents stall at high angles of attack where flow separation would
      normally occur. This behaviour is represented through the so-called 'normal
      force' model. We show that all three models can be written in the form of the
      same potential flow kernel with modifiers to account for the presence of a LEV.
      The modelling is built on previous work on quasi-steady models for hovering wings
      such that model parameters are determined from first principles, which allows a
      fair comparison between the models themselves, and the models and experimental
      data. We show that the two models which directly include the LEV as a lift
      generating component are built on a physical picture that does not represent the
      available experimental data. The simpler 'normal force' model, which does not
      explicitly model the LEV, performs best against data in the literature. We
      conclude that under steady conditions the LEV as an 'absence of stall'
      model/mechanism is the most satisfying explanation for observed aerodynamic
      behaviour.

PMID- 28747396
TI  - The mechanics of hydrogel crawlers in confined environment.
AB  - We present theoretical and experimental results regarding the development of
      temperature-sensitive hydrogel particles that can display self-motility in
      confined channels. Inspired by the motility of living organisms such as larva,
      the motion of the particle relies on the combination of two key mechanisms. The
      first, referred to as actuation, is enabled by the cyclic extension and
      retraction of the particle owing to oscillations of its temperature around the so
      called lower critical solution temperature. The second, referred to as symmetry
      breaking, transforms the isotropic particle actuation into a directed motion
      owing to the asymmetric friction properties of the channel's surface. The role of
      particle confinement in these processes is, however, less intuitive and displays
      an optimal value at which the particle's step size is maximum. These observations
      are supported by a model that identifies the underlying locomotion mechanisms and
      predicts the dependency of the particle motion efficiency on the confinement
      condition, as well as frictional properties of the substrate. Our analysis
      suggests that the existence of a lubrication layer around the particle hinders
      its motion at low confinement, while an excessive degree of confinement is
      detrimental to the particle's overall deformation and, thus, to its locomotion
      efficiency.

PMID- 28747397
TI  - Changes and classification in myocardial contractile function in the left
      ventricle following acute myocardial infarction.
AB  - In this research, we hypothesized that novel biomechanical parameters are
      discriminative in patients following acute ST-segment elevation myocardial
      infarction (STEMI). To identify these biomechanical biomarkers and bring
      computational biomechanics 'closer to the clinic', we applied state-of-the-art
      multiphysics cardiac modelling combined with advanced machine learning and
      multivariate statistical inference to a clinical database of myocardial
      infarction. We obtained data from 11 STEMI patients (ClinicalTrials.gov
      NCT01717573) and 27 healthy volunteers, and developed personalized mathematical
      models for the left ventricle (LV) using an immersed boundary method. Subject
      specific constitutive parameters were achieved by matching to clinical
      measurements. We have shown, for the first time, that compared with healthy
      controls, patients with STEMI exhibited increased LV wall active tension when
      normalized by systolic blood pressure, which suggests an increased demand on the
      contractile reserve of remote functional myocardium. The statistical analysis
      reveals that the required patient-specific contractility, normalized active
      tension and the systolic myofilament kinematics have the strongest explanatory
      power for identifying the myocardial function changes post-MI. We further
      observed a strong correlation between two biomarkers and the changes in LV
      ejection fraction at six months from baseline (the required contractility (r = -
      0.79, p < 0.01) and the systolic myofilament kinematics (r = 0.70, p = 0.02)).
      The clinical and prognostic significance of these biomechanical parameters merits
      further scrutinization.

PMID- 28747399
TI  - Cell segregation and border sharpening by Eph receptor-ephrin-mediated
      heterotypic repulsion.
AB  - Eph receptor and ephrin signalling has a major role in cell segregation and
      border formation, and may act through regulation of cell adhesion, repulsion or
      tension. To elucidate roles of cell repulsion and adhesion, we combined
      experiments in cell culture assays with quantitations of cell behaviour which are
      used in computer simulations. Cells expressing EphB2, or kinase-inactive EphB2
      (kiEphB2), segregate and form a sharp border with ephrinB1-expressing cells, and
      this is disrupted by knockdown of N-cadherin. Measurements of contact inhibition
      of locomotion reveal that EphB2-, kiEphB2- and ephrinB1-expressing cells have
      strong heterotypic and weak homotypic repulsion. EphB2 cells have a transient
      increase in migration after heterotypic activation, which underlies a shift in
      the EphB2-ephrinB1 border but is not required for segregation or border
      sharpening. Simulations with the measured values of cell behaviour reveal that
      heterotypic repulsion can account for cell segregation and border sharpening, and
      is more efficient than decreased heterotypic adhesion. By suppressing homotypic
      repulsion, N-cadherin creates a sufficient difference between heterotypic and
      homotypic repulsion, and enables homotypic cohesion, both of which are required
      to sharpen borders.

PMID- 28747398
TI  - A durable and biocompatible ascorbic acid-based covalent coating method of
      polydimethylsiloxane for dynamic cell culture.
AB  - Polydimethylsiloxane (PDMS) is widely used in dynamic biological microfluidic
      applications. As a highly hydrophobic material, native PDMS does not support cell
      attachment and culture, especially in dynamic conditions. Previous covalent
      coating methods use glutaraldehyde (GA) which, however, is cytotoxic. This paper
      introduces a novel and simple method for binding collagen type I covalently on
      PDMS using ascorbic acid (AA) as a cross-linker instead of GA. We compare the
      novel method against physisorption and GA cross-linker-based methods. The
      coatings are characterized by immunostaining, contact angle measurement, atomic
      force microscopy and infrared spectroscopy, and evaluated in static and stretched
      human adipose stem cell (hASC) cultures up to 13 days. We found that AA can
      replace GA as a cross-linker in the covalent coating method and that the coating
      is durable after sonication and after 6 days of stretching. Furthermore, we show
      that hASCs attach and proliferate better on AA cross-linked samples compared with
      physisorbed or GA-based methods. Thus, in this paper, we provide a new PDMS
      coating method for studying cells, such as hASCs, in static and dynamic
      conditions. The proposed method is an important step in the development of PDMS
      based devices in cell and tissue engineering applications.

PMID- 28747400
TI  - Dynamic disorder in simple enzymatic reactions induces stochastic amplification
      of substrate.
AB  - A growing amount of evidence over the last two decades points to the fact that
      many enzymes exhibit fluctuations in their catalytic activity, which are
      associated with conformational changes on a broad range of timescales. The
      experimental study of this phenomenon, termed dynamic disorder, has become
      possible thanks to advances in single-molecule enzymology measurement techniques,
      through which the catalytic activity of individual enzyme molecules can be
      tracked in time. The biological role and importance of these fluctuations in a
      system with a small number of enzymes, such as a living cell, have only recently
      started being explored. In this work, we examine a simple stochastic reaction
      system consisting of an inflowing substrate and an enzyme with a randomly
      fluctuating catalytic reaction rate that converts the substrate into an
      outflowing product. To describe analytically the effect of rate fluctuations on
      the average substrate abundance at steady state, we derive an explicit formula
      that connects the relative speed of enzymatic fluctuations with the mean
      substrate level. Under fairly general modelling assumptions, we demonstrate that
      the relative speed of rate fluctuations can have a dramatic effect on the mean
      substrate, and lead to large positive deviations from predictions based on the
      assumption of deterministic enzyme activity. Our results also establish an
      interesting connection between the amplification effect and the mixing properties
      of the Markov process describing the enzymatic activity fluctuations, which can
      be used to easily predict the fluctuation speed above which such deviations
      become negligible. As the techniques of single-molecule enzymology continuously
      evolve, it may soon be possible to study the stochastic phenomena due to
      enzymatic activity fluctuations within living cells. Our work can be used to
      formulate experimentally testable hypotheses regarding the nature and magnitude
      of these fluctuations, as well as their phenotypic consequences.

PMID- 28747401
TI  - Influence of scene structure and content on visual search strategies.
AB  - When searching for a target within an image, our brain can adopt different
      strategies, but which one does it choose? This question can be answered by
      tracking the motion of the eye while it executes the task. Following many
      individuals performing various search tasks, we distinguish between two competing
      strategies. Motivated by these findings, we introduce a model that captures the
      interplay of the search strategies and allows us to create artificial eye
      tracking trajectories, which could be compared with the experimental ones.
      Identifying the model parameters allows us to quantify the strategy employed in
      terms of ensemble averages, characterizing each experimental cohort. In this way,
      we can discern with high sensitivity the relation between the visual landscape
      and the average strategy, disclosing how small variations in the image induce
      changes in the strategy.

PMID- 28747402
TI  - Default mode network neurodegeneration reveals the remote effects of ischaemic
      stroke.

PMID- 28747403
TI  - Agmatine: multifunctional arginine metabolite and magic bullet in clinical
      neuroscience?
AB  - Agmatine, the decarboxylation product of arginine, was largely neglected as an
      important player in mammalian metabolism until the mid-1990s, when it was re
      discovered as an endogenous ligand of imidazoline and alpha2-adrenergic
      receptors. Since then, a wide variety of agmatine-mediated effects have been
      observed, and consequently agmatine has moved from a wallflower existence into
      the limelight of clinical neuroscience research. Despite this quantum jump in
      scientific interest, the understanding of the anabolism and catabolism of this
      amine is still vague. The purification and biochemical characterization of
      natural mammalian arginine decarboxylase and agmatinase still are open issues.
      Nevertheless, the agmatinergic system is currently one of the most promising
      candidates in order to pharmacologically interfere with some major diseases of
      the central nervous system, which are summarized in the present review.
      Particularly with respect to major depression, agmatine, its derivatives, and
      metabolizing enzymes show great promise for the development of an improved
      treatment of this common disease.

PMID- 28747404
TI  - Galectin-8 regulates targeting of Gp135/podocalyxin and lumen formation at the
      apical surface of renal epithelial cells.
AB  - Establishment of apical-basal polarity, through correct targeting of polarity
      determinants to distinct domains of the plasma membrane, is a fundamental process
      for the development of functioning epithelial tubules. Here we report that
      galectin (Gal)-8 regulates apical-basal polarity of Madin-Darby canine kidney
      (MDCK) cells via apical targeting of 135-kDa glycoprotein (Gp135). Gal-8
      interacts with newly synthesized Gp135 in a glycan-dependent manner. Gal-8
      knockdown induces aberrant lumens at the lateral domain and mistargeting of Gp135
      to this structure, thus disrupting the kidney epithelial polarity of MDCK cells,
      which organize lumens at the apical surface. The O-glycosylation deletion mutant
      of Gp135 phenocopies the effect of Gal-8 knockdown, which suggests that Gal-8 is
      the decoding machinery for the apical sorting signals of Gp135 residing at its O
      glycosylation-rich region. Collectively, our results reveal a new role of Gal-8
      in the development of luminal organs by regulating targeting of apical polarity
      protein Gp135.-Lim, H., Yu, C.-Y., Jou, T.-S. Galectin-8 regulates targeting of
      Gp135/podocalyxin and lumen formation at the apical surface of renal epithelial
      cells.

PMID- 28747405
TI  - NMDA receptor-dependent presynaptic inhibition at the calyx of Held synapse of
      rat pups.
AB  - N-Methyl-d-aspartate receptors (NMDARs) play diverse roles in synaptic
      transmission, synaptic plasticity, neuronal development and neurological
      diseases. In addition to their postsynaptic expression, NMDARs are also expressed
      in presynaptic terminals at some central synapses, and their activation modulates
      transmitter release. However, the regulatory mechanisms of NMDAR-dependent
      synaptic transmission remain largely unknown. In the present study, we
      demonstrated that activation of NMDARs in a nerve terminal at a central
      glutamatergic synapse inhibits presynaptic Ca2+ currents (ICa) in a GluN2C/2D
      subunit-dependent manner, thereby decreasing nerve-evoked excitatory postsynaptic
      currents. Neither presynaptically loaded fast Ca2+ chelator BAPTA nor non
      hydrolysable GTP analogue GTPgammaS affected NMDAR-mediated ICa inhibition. In
      the presence of a glutamate uptake blocker, the decline in ICa amplitude evoked
      by repetitive depolarizing pulses at 20 Hz was attenuated by an NMDAR competitive
      antagonist, suggesting that endogenous glutamate has a potential to activate
      presynaptic NMDARs. Moreover, NMDA-induced inward currents at a negative holding
      potential (-80 mV) were abolished by intra-terminal loading of the NMDAR open
      channel blocker MK-801, indicating functional expression of presynaptic NMDARs.
      We conclude that presynaptic NMDARs can attenuate glutamate release by inhibiting
      voltage-gated Ca2+ channels at a relay synapse in the immature rat auditory
      brainstem.

PMID- 28747406
TI  - lncRNAs in development and disease: from functions to mechanisms.
AB  - Differential expression of long non-coding RNAs (lncRNAs) during differentiation
      and their misregulation in cancer highlight their potential as cell fate
      regulators. While some example lncRNAs have been characterized in great detail,
      the functional in vivo relevance of others has been called into question. Finding
      functional lncRNAs will most probably require a combination of complementary
      approaches that will greatly vary depending on their mode of action. In this
      review, we discuss the different tools available to dissect genetically lncRNA
      requirements and how each is best suited to studies in particular contexts.
      Moreover, we review different strategies used to select candidate lncRNAs and
      give an overview of lncRNAs described to regulate development and cancer through
      different mechanisms.

PMID- 28747407
TI  - Chronic hindbrain administration of oxytocin is sufficient to elicit weight loss
      in diet-induced obese rats.
AB  - Oxytocin (OT) administration elicits weight loss in diet-induced obese (DIO)
      rodents, nonhuman primates, and humans by reducing energy intake and increasing
      energy expenditure. Although the neurocircuitry underlying these effects remains
      uncertain, OT neurons in the paraventricular nucleus are positioned to control
      both energy intake and sympathetic nervous system outflow to interscapular brown
      adipose tissue (BAT) through projections to the hindbrain nucleus of the solitary
      tract and spinal cord. The current work was undertaken to examine whether central
      OT increases BAT thermogenesis, whether this effect involves hindbrain OT
      receptors (OTRs), and whether such effects are associated with sustained weight
      loss following chronic administration. To assess OT-elicited changes in BAT
      thermogenesis, we measured the effects of intracerebroventricular administration
      of OT on interscapular BAT temperature in rats and mice. Because fourth
      ventricular (4V) infusion targets hindbrain OTRs, whereas third ventricular (3V)
      administration targets both forebrain and hindbrain OTRs, we compared responses
      to OT following chronic 3V infusion in DIO rats and mice and chronic 4V infusion
      in DIO rats. We report that chronic 4V infusion of OT into two distinct rat
      models recapitulates the effects of 3V OT to ameliorate DIO by reducing fat mass.
      While reduced food intake contributes to this effect, our finding that 4V OT also
      increases BAT thermogenesis suggests that increased energy expenditure may
      contribute as well. Collectively, these findings support the hypothesis that, in
      DIO rats, OT action in the hindbrain evokes sustained weight loss by reducing
      energy intake and increasing BAT thermogenesis.

PMID- 28747408
TI  - Respiratory muscle endurance training reduces the O2 cost of cycling and
      perceived exertion in obese adolescents.
AB  - In obesity, the increased O2 cost of breathing negatively affects the O2 cost of
      exercise and exercise tolerance. The purpose of the study was to determine
      whether, in obese adolescents, the addition of respiratory muscle endurance
      training (RMET) (isocapnic hyperpnea) to a standard body mass reduction program
      decreases the O2 cost of exercise and perceived exertion. Nine male obese
      adolescents [16.0 +/- 1.4 yr (x +/- SD), body mass 114.4 +/- 22.3 kg] underwent 3
      wk of RMET (5 days/week) in addition to a standard body mass reduction program.
      Eight age- and sex-matched obese adolescents underwent only the standard program
      (CTRL). Before and after interventions, patients performed on a cycle ergometer:
      incremental exercise; 12-min exercises at a constant work rate (CWR) of 65% and
      120% at the gas exchange threshold (GET) determined before the intervention.
      Breath-by-breath pulmonary ventilation (Ve) and O2 uptake (Vo2), heart rate (HR),
      and ratings of perceived exertion for dyspnea/respiratory discomfort (RPER) and
      leg effort (RPEL) were determined. Body mass decreased (by ~3.0 kg) after both
      RMET (P = 0.003) and CTRL (P = 0.002). Peak Vo2 was not affected by both
      interventions. Peak work rate was slightly, but significantly (P = 0.04), greater
      after RMET but not after CTRL. During CWR < GET, no changes were observed after
      both interventions. During CWR > GET, the O2 cost of cycling at the end of
      exercise (P = 0.02), the slope of Vo2 vs. time (3-12 min) (P = 0.01), RPER (P =
      0.01), and RPEL (P = 0.01) decreased following RMET, but not following CTRL. HR
      decreased after both RMET (P = 0.02) and CTRL (P = 0.03), whereas Ve did not
      change. In obese adolescents RMET, superimposed on a standard body mass reduction
      program, lowered the O2 cost of cycling and perceived exertion during constant
      heavy-intensity exercise.

PMID- 28747409
TI  - Spot urine protein measurements in normotensive pregnancies, pregnancies with
      isolated proteinuria and preeclampsia.
AB  - We performed a prospective, longitudinal study of pregnant women presenting to
      their first obstetrics visits to characterize the changes in spot urine protein
      to-creatinine (UPCR) and albumin-to-creatinine ratios (UACR) in normotensive
      pregnancies, as well as identify clinical characteristics associated with
      isolated proteinuria and preeclampsia. We measured spot urinary albumin, protein,
      and creatinine at the first prenatal visit, end of the second trimester, and at
      delivery. In the normotensive pregnancies (n = 142), we found that from the
      beginning of pregnancy to delivery, UACR increased by a median [interquartile
      range (IQR)] of 14.7 mg/g Cr (3.74-51.8) and UPCR by 60 mg/g Cr (30-130) (P <
      0.001 for both changes). Isolated proteinuria (defined as UPCR > 300 mg/g Cr in
      the absence of hypertension) was identified in 19/142 (13.4%) normotensive
      pregnancies. Increases in systolic and diastolic blood pressure from early
      pregnancy to delivery and increases in UACR from early to midpregnancy were
      associated with isolated proteinuria at delivery. Twelve women developed
      preeclampsia. Nulliparity, early, and midpregnancy diastolic blood pressures were
      strongly associated with the development of preeclampsia, but early changes in
      UACR were not. In conclusion, women who develop isolated proteinuria at delivery
      have a larger increase in blood pressure than women without proteinuria and have
      a "microalbuminuric" phase earlier in gestation, unlike women who develop
      preeclampsia. These findings suggest a different mechanism of urine protein
      excretion in women with isolated proteinuria as compared with women with
      preeclampsia, where proteinuria has a more abrupt onset.

PMID- 28747410
TI  - A systematic review and meta-analysis of studies evaluating the performance and
      operational characteristics of dual point-of-care tests for HIV and syphilis.
AB  - BACKGROUND: Mother-to-child transmission (MTCT) of syphilis and HIV continue to
      be important yet preventable causes of perinatal and infant morbidity and
      mortality. OBJECTIVES: To systematically review, critically appraise and perform
      a meta-analysis to evaluate the operational characteristics of dual rapid
      diagnostic tests (RDTs) for HIV/syphilis and evaluate whether they are cost
      effective, acceptable and easy to use. DESIGN: Systematic review and meta
      analysis. DATA SOURCES: We searched seven electronic bibliographic databases from
      2012 to December 2016 with no language restrictions. Search keywords included
      HIV, syphilis and diagnosis. REVIEW METHODS: We included studies that evaluated
      the operational characteristics of dual HIV/syphilis RDTs. Outcomes included
      diagnostic test accuracy, cost effectiveness, ease of use and interpretation and
      acceptability. All studies were assessed against quality criteria and assessed
      for risk of bias. RESULTS: Of 1914 identified papers, 18 were included for the
      meta-analysis of diagnostic accuracy for HIV and syphilis. All diagnostic
      accuracy evaluation studies showed a very high sensitivity and specificity for
      HIV and a lower, yet adequate, sensitivity and specificity for syphilis, with
      some variation among types of test. Dual screening for HIV and syphilis was more
      cost effective than single rapid tests for HIV and syphilis and prevented more
      adverse pregnancy outcomes. Qualitative data suggested dual RDTs were highly
      acceptable to clients, who cited time to result, cost and the requirement of a
      single finger prick as important characteristics of dual RDTs. CONCLUSION: The
      results of this systematic review and meta-analysis can be used by policy-makers
      and national programme managers who are considering implementing dual RDTs for
      HIV and syphilis. TRIAL REGISTRATION NUMBER: PROSPERO 2016:CRD42016049168.

PMID- 28747411
TI  - Stroke of the inferiomedial temporal lobe causing word agnosia.
AB  - A 69-year-old man presented with sudden loss of ability to recognise written
      words and remember the meaning of words and names. He could not name the town he
      lived in nor name his children. It was difficult for him to remember the meaning
      of concrete and abstract nouns. His speech fluency and understanding of casual
      talks were normal. He remembered that he had a conversation with his family that
      morning, but not the exact content. He was referred to the transient ischaemic
      attack clinic by his general practitioner as he scored low on the abbreviated
      mental test score. He underwent a brain MRI scan (T2 weighted, diffusion weighted
      and fluid-attenuated inversion recovery) which showed an acute infarction in the
      left medial temporal region affecting the fusiform and parahippocampal gyri. He
      also noticed that it was easier to retrieve numbers, for example, his mobile
      number. He recovered on waking up the next day.

PMID- 28747413
TI  - Barium aspiration through a tracheo-oesophageal fistula caused by percutaneous
      tracheostomy.

PMID- 28747412
TI  - Severe asymptomatic rhabdomyolysis complicating a mycoplasma pneumonia.
AB  - Rhabdomyolysis is a very rare and serious extrapulmonary manifestation of a
      Mycoplasma pneumoniae infection. We describe a case of a 47-year-old male patient
      who presented with progressive dyspnoea, hypoxaemia and cough during the last 3
      days. He had no relevant muscular complaints but was diagnosed with severe
      rhabdomyolysis for which he was treated with hyperhydration. Molecular
      diagnostics confirmed M. pneumoniae as the causative agent and our patient was
      successfully treated with doxycycline.Only a few cases of rhabdomyolysis
      complicating a M. pneumoniae infection have been described, mostly in infants. In
      this case, typical suggestive complaints of rhabdomyolysis were absent suggesting
      that the complication might be underdiagnosed.

PMID- 28747414
TI  - Muscular sarcocystosis: an index case in a native Malaysian.
AB  - A previously healthy 20-year-old man presented with prolonged intermittent low
      grade fever and cough for 6months. He had bilateral calf pain and lower limb
      weakness 2days prior to admission. Physical examination revealed multiple
      enlarged lymph nodes with hepatomegaly. There was bilateral calf tenderness with
      evidence of proximal myopathy. Full blood picture showed lymphocytosis with
      reactive lymphocytes and eosinophilia. Creatine kinase and lactate dehydrogenase
      were markedly elevated. Over 2 weeks of admission, patient was treated
      symptomatically until the muscle biopsy of right calf revealed eosinophilic
      myositis with muscular sarcocystosis. He was treated with albendazole and high
      dose corticosteroids. Symptoms subsided on reviewed at 2weeks and the dose of
      corticosteroid was tapered down slowly over a month. Due to poor compliance, he
      was readmitted 1month later because of relapsed. High-dose corticosteroid was
      restarted and duration for albendazole was prolonged for 1month. His symptom
      finally resolved over 2weeks.

PMID- 28747415
TI  - Migration of intraocular silicone oil into brain.

PMID- 28747416
TI  - Discitis and Clostridium perfringens bacteraemia.
AB  - The authors present a case involving an 80-year-old man with infectious T10/T11
      discitis on the background of a recent Clostridium perfringens bacteraemia. This
      case report describes a case of probable C. perfringens discitis as further
      investigations failed to identify any causative agents. He was treated with
      intravenous piperacillin/tazobactam to good effect, achieving favourable clinical
      outcome. Diagnosis of discitis/osteomyelitis can often be delayed and mismanaged
      due to its non-specific presentations. Timing of empirical antimicrobial therapy
      requires careful consideration based on haemodynamic stability and neurological
      function to maximise microbiological yield.

PMID- 28747417
TI  - A rare case of an ectopic pregnancy in the rudimentary tube of a patient with an
      isolated unicornuate uterus.
AB  - Uterine anomalies are relatively uncommon and go undiagnosed in many cases.
      Ectopic pregnancies have been reported in such patients, although rarely, in the
      non-communicating rudimentary horns of unicornuate uteri. However, the case
      presented is of an ectopic pregnancy in the rudimentary fallopian tube related to
      an undescended ovary in a patient with an isolated unicornuate uterus, a
      phenomenon which is extremely rare.

PMID- 28747418
TI  - A complication of meningitis and infective endocarditis due to Streptococcus
      pyogenes.
AB  - We described a rare case of meningitis and infective endocarditis (IE) due to
      Streptococcus pyogenes. An 80-year-old woman was admitted to our hospital with
      unconsciousness. Glasgow Coma Scale was E1V3M5. We diagnosed her with acute
      meningitis due to S. pyogenes and started treatment using ceftriaxone. In spite
      of the improvement of her unconscious state, she developed a new-onset systolic
      murmur on day 13, and echocardiography revealed severe mitral valve regurgitation
      with vegetation. Therefore, we also diagnosed her with IE and continued the
      antibiotics for 6 weeks after we confirmed the negative blood cultures. The
      patient was finally transferred to another hospital for rehabilitation 57 days
      after admission. Considering that the number of S. pyogenes infections has been
      reported to increase in Japan and worldwide, we need to be more careful about the
      rare complication of meningitis and IE due to S. pyogenes.

PMID- 28747419
TI  - Unusual case of odontogenic maxillary sinusitis.

PMID- 28747420
TI  - Reply: The BIF Domain Is Structurally and Functionally Distinct from Other Types
      of ACT-Like Domains.

PMID- 28747421
TI  - The BIF Domain in Plant bHLH Proteins Is an ACT-Like Domain.

PMID- 28747423
TI  - Impact of Physician Specialty Mix on the Outcomes of Patients Dually Diagnosed
      With Diabetes and Compensated Cirrhosis.

PMID- 28747422
TI  - Suppressing a Putative Sterol Carrier Gene Reduces Plasmodesmal Permeability and
      Activates Sucrose Transporter Genes during Cotton Fiber Elongation.
AB  - Plasmodesmata (PDs) play vital roles in cell-to-cell communication and plant
      development. Emerging evidence suggests that sterols are involved in PD activity
      during cytokinesis. However, whether sterols contribute to PD gating between
      established cells remains unknown. Here, we isolated GhSCP2D, a putative sterol
      carrier protein gene from elongating cotton (Gossypium hirsutum) fibers. In
      contrast to wild-type fiber PDs, which opened at 5 to 10 d postanthesis (DPA) and
      closed only at 15 to 25 DPA, plants with suppressed GhSCP2D expression had
      reduced sterol contents and closed PDs at 5 through 25 DPA The GhSCP2D-suppressed
      fibers exhibited callose deposition at the PDs, likely due to reduced expression
      of GhPdBG3-2A/D, which encodes a PD-targeting beta-1,3-glucanase. Both GhPdBG3
      2A/D expression and callose deposition were sensitive to a sterol biosynthesis
      inhibitor. Moreover, suppressing GhSCP2D upregulated a cohort of SUT and SWEET
      sucrose transporter genes in fiber cells. Collectively, our results indicate that
      (1) GhSCP2D is required for GhPdBG3-2A/D expression to degrade callose at the PD,
      thereby contributing to the establishment of the symplasmic pathway; and (2)
      blocking the symplasmic pathway by downregulating GhSCP2D activates or increases
      the expression of SUTs and SWEETs, leading to the switch from symplasmic to
      apoplasmic pathways.

PMID- 28747425
TI  - JEM Advisory Editorial Board: Increasing diversity.

PMID- 28747424
TI  - ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control.
AB  - Group 2 innate lymphoid cells (ILC2s) are important effector cells driving the
      initiation of type 2 immune responses leading to adaptive T helper 2 (Th2)
      immunity. Here we show that ILC2s dynamically express the checkpoint inhibitor
      molecule PD-L1 during type 2 pulmonary responses. Surprisingly, PD-L1:PD-1
      interaction between ILC2s and CD4+ T cells did not inhibit the T cell response,
      but PD-L1-expressing ILC2s stimulated increased expression of GATA3 and
      production of IL-13 by Th2 cells both in vitro and in vivo. Conditional deletion
      of PD-L1 on ILC2s impaired early Th2 polarization and cytokine production,
      leading to delayed worm expulsion during infection with the gastrointestinal
      helminth Nippostrongylus brasiliensis Our results identify a novel PD-L1
      controlled mechanism for type 2 polarization, with ILC2s mediating an innate
      checkpoint to control adaptive T helper responses, which has important
      implications for the treatment of type 2 inflammation.

PMID- 28747426
TI  - Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up
      regulation and NKG2D-mediated inflammation.
AB  - Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial
      cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as
      shown by mice with IEC-specific deletion of X-box-binding protein 1 (Xbp1), an
      unfolded protein response-related transcription factor. In this study, Xbp1
      deletion in the epithelium (Xbp1DeltaIEC ) is shown to cause increased expression
      of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding
      protein (ULBP)-like transcript 1 and its human orthologue cytomegalovirus ULBP
      via ER stress-related transcription factor C/EBP homology protein. Increased
      NKG2DL expression on mouse IECs is associated with increased numbers of
      intraepithelial NKG2D-expressing group 1 innate lymphoid cells (ILCs; NK cells or
      ILC1). Blockade of NKG2D suppresses cytolysis against ER-stressed epithelial
      cells in vitro and spontaneous enteritis in vivo. Pharmacological depletion of
      NK1.1+ cells also significantly improved enteritis, whereas enteritis was not
      ameliorated in Recombinase activating gene 1-/-;Xbp1DeltaIEC mice. These
      experiments reveal innate immune sensing of ER stress in IECs as an important
      mechanism of intestinal inflammation.

PMID- 28747427
TI  - A biallelic mutation in IL6ST encoding the GP130 co-receptor causes
      immunodeficiency and craniosynostosis.
AB  - Multiple cytokines, including interleukin 6 (IL-6), IL-11, IL-27, oncostatin M
      (OSM), and leukemia inhibitory factor (LIF), signal via the common GP130 cytokine
      receptor subunit. In this study, we describe a patient with a homozygous mutation
      of IL6ST (encoding GP130 p.N404Y) who presented with recurrent infections,
      eczema, bronchiectasis, high IgE, eosinophilia, defective B cell memory, and an
      impaired acute-phase response, as well as skeletal abnormalities including
      craniosynostosis. The p.N404Y missense substitution is associated with loss of IL
      6, IL-11, IL-27, and OSM signaling but a largely intact LIF response. This study
      identifies a novel immunodeficiency with phenotypic similarities to STAT3 hyper
      IgE syndrome caused by loss of function of GP130.

PMID- 28747428
TI  - Sequence Exchange between Homologous NB-LRR Genes Converts Virus Resistance into
      Nematode Resistance, and Vice Versa.
AB  - Plants have evolved a limited repertoire of NB-LRR disease resistance (R) genes
      to protect themselves against myriad pathogens. This limitation is thought to be
      counterbalanced by the rapid evolution of NB-LRR proteins, as only a few sequence
      changes have been shown to be sufficient to alter resistance specificities toward
      novel strains of a pathogen. However, little is known about the flexibility of NB
      LRR R genes to switch resistance specificities between phylogenetically unrelated
      pathogens. To investigate this, we created domain swaps between the close
      homologs Gpa2 and Rx1, which confer resistance in potato (Solanum tuberosum) to
      the cyst nematode Globodera pallida and Potato virus X, respectively. The genetic
      fusion of the CC-NB-ARC of Gpa2 with the LRR of Rx1 (Gpa2CN/Rx1L) results in
      autoactivity, but lowering the protein levels restored its specific activation
      response, including extreme resistance to Potato virus X in potato shoots. The
      reciprocal chimera (Rx1CN/Gpa2L) shows a loss-of-function phenotype, but exchange
      of the first three LRRs of Gpa2 by the corresponding region of Rx1 was sufficient
      to regain a wild-type resistance response to G. pallida in the roots. These data
      demonstrate that exchanging the recognition moiety in the LRR is sufficient to
      convert extreme virus resistance in the leaves into mild nematode resistance in
      the roots, and vice versa. In addition, we show that the CC-NB-ARC can operate
      independently of the recognition specificities defined by the LRR domain, either
      aboveground or belowground. These data show the versatility of NB-LRR genes to
      generate resistance to unrelated pathogens with completely different lifestyles
      and routes of invasion.

PMID- 28747429
TI  - The hepatic circadian clock fine-tunes the lipogenic response to feeding through
      RORalpha/gamma.
AB  - Liver lipid metabolism is under intricate temporal control by both the circadian
      clock and feeding. The interplay between these two mechanisms is not clear. Here
      we show that liver-specific depletion of nuclear receptors RORalpha and RORgamma,
      key components of the molecular circadian clock, up-regulate expression of
      lipogenic genes only under fed conditions at Zeitgeber time 22 (ZT22) but not
      under fasting conditions at ZT22 or ad libitum conditions at ZT10. RORalpha/gamma
      controls circadian expression of Insig2, which keeps feeding-induced SREBP1c
      activation under check. Loss of RORalpha/gamma causes overactivation of the SREBP
      dependent lipogenic response to feeding, exacerbating diet-induced hepatic
      steatosis. These findings thus establish ROR/INSIG2/SREBP as a molecular pathway
      by which circadian clock components anticipatorily regulate lipogenic responses
      to feeding. This highlights the importance of time of day as a consideration in
      the treatment of liver metabolic disorders.

PMID- 28747431
TI  - Reconfiguring what is owed to patients in planning and delivering health care.

PMID- 28747430
TI  - Ferredoxin reductase is critical for p53-dependent tumor suppression via iron
      regulatory protein 2.
AB  - Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis
      and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To
      determine the biological function of FDXR, we generated a Fdxr-deficient mouse
      model and found that loss of Fdxr led to embryonic lethality potentially due to
      iron overload in developing embryos. Interestingly, mice heterozygous in Fdxr had
      a short life span and were prone to spontaneous tumors and liver abnormalities,
      including steatosis, hepatitis, and hepatocellular carcinoma. We also found that
      FDXR was necessary for mitochondrial iron homeostasis and proper expression of
      several master regulators of iron metabolism, including iron regulatory protein 2
      (IRP2). Surprisingly, we found that p53 mRNA translation was suppressed by FDXR
      deficiency via IRP2. Moreover, we found that the signal from FDXR to iron
      homeostasis and the p53 pathway was transduced by ferredoxin 2, a substrate of
      FDXR. Finally, we found that p53 played a role in iron homeostasis and was
      required for FDXR-mediated iron metabolism. Together, we conclude that FDXR and
      p53 are mutually regulated and that the FDXR-p53 loop is critical for tumor
      suppression via iron homeostasis.

PMID- 28747432
TI  - Ethics briefing.

PMID- 28747433
TI  - Efficient methylation of C2 in l-tryptophan by the cobalamin-dependent radical S
      adenosylmethionine methylase TsrM requires an unmodified N1 amine.
AB  - TsrM catalyzes the methylation of C2 in l-tryptophan (Trp). This reaction is the
      first step in the biosynthesis of the quinaldic acid moiety of the thiopeptide
      antibiotic thiostrepton, which exhibits potent activity against Gram-positive
      pathogens. TsrM is a member of the radical S-adenosylmethionine (SAM) superfamily
      of enzymes, but it does not catalyze the formation of 5'-deoxyadenosin-5'-yl or
      any other SAM-derived radical. In addition to a [4Fe-4S] cluster, TsrM contains a
      cobalamin cofactor that serves as an intermediate methyl carrier in its reaction.
      However, how this cofactor donates a methyl moiety to the Trp substrate is
      unknown. Here, we showed that the unmodified N1 position of Trp is important for
      turnover and that 1-thia-Trp and 1-oxa-Trp serve as competitive inhibitors. We
      also showed that beta-cyclopropyl-Trp undergoes C2 methylation in the absence of
      cyclopropyl ring opening, disfavoring mechanisms that involve unpaired electron
      density at C3 of the indole ring. Moreover, we showed that all other indole
      substituted analogs of Trp undergo methylation at varying but measurable rates
      and that the analog 7-aza-Trp, which is expected to temper the nucleophilicity of
      C2 in Trp, is a very poor substrate. Last, no formation of cob(II)alamin or
      substrate radicals was observed during the reaction with Trp or any molecule
      within a tested panel of Trp analogs. In summary, our results are most consistent
      with a mechanism that involves two polar nucleophilic displacements, the second
      of which requires deprotonation of the indole nitrogen in Trp during its attack
      on methylcobalamin.

PMID- 28747434
TI  - Thrombospondin-1 (TSP-1), a new bone morphogenetic protein-2 and -4 (BMP-2/4)
      antagonist identified in pituitary cells.
AB  - Bone morphogenetic proteins (BMPs) regulate diverse cellular responses during
      embryogenesis and in adulthood including cell differentiation, proliferation, and
      death in various tissues. In the adult pituitary, BMPs participate in the control
      of hormone secretion and cell proliferation, suggesting a potential
      endocrine/paracrine role for BMPs, but some of the mechanisms are unclear. Here,
      using a bioactivity test based on embryonic cells (C3H10T1/2) transfected with a
      BMP-responsive element, we sought to determine whether pituitary cells secrete
      BMPs or BMP antagonists. Interestingly, we found that pituitary-conditioned
      medium contains a factor that inhibits action of BMP-2 and -4. Combining surface
      plasmon resonance and high-resolution mass spectrometry helped pinpoint this
      factor as thrombospondin-1 (TSP-1). Surface plasmon resonance and co
      immunoprecipitation confirmed that recombinant human TSP-1 can bind BMP-2 and -4
      and antagonize their effects on C3H10T1/2 cells. Moreover, TSP-1 inhibited the
      action of serum BMPs. We also report that the von Willebrand type C domain of TSP
      1 is likely responsible for this BMP-2/4-binding activity, an assertion based on
      sequence similarity that TSP-1 shares with the von Willebrand type C domain of
      Crossveinless 2 (CV-2), a BMP antagonist and member of the chordin family. In
      summary, we identified for the first time TSP-1 as a BMP-2/-4 antagonist and
      presented a structural basis for the physical interaction between TSP-1 and BMP
      4. We propose that TSP-1 could regulate bioavailability of BMPs, either produced
      locally or reaching the pituitary via blood circulation. In conclusion, our
      findings provide new insights into the involvement of TSP-1 in the BMP-2/-4
      mechanisms of action.

PMID- 28747435
TI  - Search for DNA damage by human alkyladenine DNA glycosylase involves early
      intercalation by an aromatic residue.
AB  - DNA repair enzymes recognize and remove damaged bases that are embedded in the
      duplex. To gain access, most enzymes use nucleotide flipping, whereby the target
      nucleotide is rotated 180 degrees  into the active site. In human alkyladenine
      DNA glycosylase (AAG), the enzyme that initiates base excision repair of
      alkylated bases, the flipped-out nucleotide is stabilized by intercalation of the
      side chain of tyrosine 162 that replaces the lesion nucleobase. Previous kinetic
      studies provided evidence for the formation of a transient complex that precedes
      the stable flipped-out complex, but it is not clear how this complex differs from
      nonspecific complexes. We used site-directed mutagenesis and transient-kinetic
      approaches to investigate the timing of Tyr162 intercalation for AAG. The
      tryptophan substitution (Y162W) appeared to be conservative, because the mutant
      protein retained a highly favorable equilibrium constant for flipping the 1,N6
      ethenoadenine (epsilonA) lesion, and the rate of N-glycosidic bond cleavage was
      identical to that of the wild-type enzyme. We assigned the tryptophan
      fluorescence signal from Y162W by removing two native tryptophan residues
      (W270A/W284A). Stopped-flow experiments then demonstrated that the change in
      tryptophan fluorescence of the Y162W mutant is extremely rapid upon binding to
      either damaged or undamaged DNA, much faster than the lesion-recognition and
      nucleotide flipping steps that were independently determined by monitoring the
      epsilonA fluorescence. These observations suggest that intercalation by this
      aromatic residue is one of the earliest steps in the search for DNA damage and
      that this interaction is important for the progression of AAG from nonspecific
      searching to specific-recognition complexes.

PMID- 28747436
TI  - The Alzheimer's disease-protective CD33 splice variant mediates adaptive loss of
      function via diversion to an intracellular pool.
AB  - The immunomodulatory receptor Siglec-3/CD33 influences risk for late-onset
      Alzheimer's disease (LOAD), an apparently human-specific post-reproductive
      disease. CD33 generates two splice variants: a full-length CD33M transcript
      produced primarily by the "LOAD-risk" allele and a shorter CD33m isoform lacking
      the sialic acid-binding domain produced primarily from the "LOAD-protective"
      allele. An SNP that modulates CD33 splicing to favor CD33m is associated with
      enhanced microglial activity. Individuals expressing more protective isoform
      accumulate less brain beta-amyloid and have a lower LOAD risk. How the CD33m
      isoform increases beta-amyloid clearance remains unknown. We report that the
      protection by the CD33m isoform may not be conferred by what it does but, rather,
      from what it cannot do. Analysis of blood neutrophils and monocytes and a
      microglial cell line revealed that unlike CD33M, the CD33m isoform does not
      localize to cell surfaces; instead, it accumulates in peroxisomes. Cell
      stimulation and activation did not mobilize CD33m to the surface. Thus, the CD33m
      isoform may neither interact directly with amyloid plaques nor engage in cell
      surface signaling. Rather, production and localization of CD33m in peroxisomes is
      a way of diminishing the amount of CD33M and enhancing beta-amyloid clearance. We
      confirmed intracellular localization by generating a CD33m-specific monoclonal
      antibody. Of note, CD33 is the only Siglec with a peroxisome-targeting sequence,
      and this motif emerged by convergent evolution in toothed whales, the only other
      mammals with a prolonged post-reproductive lifespan. The CD33 allele that
      protects post-reproductive individuals from LOAD may have evolved by adaptive
      loss-of-function, an example of the less-is-more hypothesis.

PMID- 28747437
TI  - Crystal structure of the human Polepsilon B-subunit in complex with the C
      terminal domain of the catalytic subunit.
AB  - The eukaryotic B-family DNA polymerases include four members: Polalpha, Poldelta,
      Polepsilon, and Polzeta, which share common architectural features, such as the
      exonuclease/polymerase and C-terminal domains (CTDs) of catalytic subunits bound
      to indispensable B-subunits, which serve as scaffolds that mediate interactions
      with other components of the replication machinery. Crystal structures for the B
      subunits of Polalpha and Poldelta/Polzeta have been reported: the former within
      the primosome and separately with CTD and the latter with the N-terminal domain
      of the C-subunit. Here we present the crystal structure of the human Polepsilon B
      subunit (p59) in complex with CTD of the catalytic subunit (p261C). The structure
      revealed a well defined electron density for p261C and the phosphodiesterase and
      oligonucleotide/oligosaccharide-binding domains of p59. However, electron density
      was missing for the p59 N-terminal domain and for the linker connecting it to the
      phosphodiesterase domain. Similar to Polalpha, p261C of Polepsilon contains a
      three-helix bundle in the middle and zinc-binding modules on each side.
      Intersubunit interactions involving 11 hydrogen bonds and numerous hydrophobic
      contacts account for stable complex formation with a buried surface area of 3094
      A2 Comparative structural analysis of p59-p261C with the corresponding Polalpha
      complex revealed significant differences between the B-subunits and CTDs, as well
      as their interaction interfaces. The B-subunit of Poldelta/Polzeta also
      substantially differs from B-subunits of either Polalpha or Polepsilon. This work
      provides a structural basis to explain biochemical and genetic data on the
      importance of B-subunit integrity in replisome function in vivo.

PMID- 28747438
TI  - Palmitoylation is a prerequisite for dimerization-dependent raftophilicity of
      rhodopsin.
AB  - The visual photopigment rhodopsin (Rh) is a prototypical G protein-coupled
      receptor (GPCR) responsible for initiation of the phototransduction cascade in
      rod photoreceptors. Similar to other GPCRs, Rh can form dimers or even higher
      oligomers and tends to have a supramolecular organization that is likely
      important in the dim light response. Rh also exhibits high affinity for lipid
      rafts (i.e. raftophilicity) upon light-dependent binding with the cognate G
      protein transducin (Gt), suggesting the presence of lipid raft-like domains in
      the retinal disk membrane and their importance in phototransduction. However, the
      relationship between Rh oligomerization and lipid rafts in the disk membrane
      remains to be explored. Given previous findings that Gt binds to dimeric Rh and
      that Rh is posttranslationally modified with two highly raftophilic palmitoyl
      moieties, we hypothesized that Rh becomes raftophilic upon dimerization. Here,
      using biochemical assays, we found that Rh*-Gt complexes in the detergent
      resistant membrane are partially resistant to cholesterol depletion by methyl
      beta-cyclodextrin and that the Rh-to-Gt stoichiometry in this methyl-beta
      cyclodextrin-resistant complex is 2:1. Next, we found that IgG-mediated Rh-Rh
      cross-linking renders Rh highly raftophilic, supporting the premise that Rh
      becomes raftophilic upon dimerization. Rh depalmitoylation via reduction of
      thioester linkages blocked the translocation of IgG-cross-linked Rh to the
      detergent-resistant membrane, highlighting that the two palmitoyl moieties are
      important for the dimerization-dependent raftophilicity of Rh. These results
      indicate that palmitoylated GPCRs such as Rh can acquire raftophilicity upon G
      protein-stabilized dimerization and thereby organize receptor-cluster rafts by
      recruiting raftophilic lipids.

PMID- 28747439
TI  - Diverse mitotic functions of the cytoskeletal cross-linking protein Shortstop
      suggest a role in Dynein/Dynactin activity.
AB  - Proper assembly and orientation of the bipolar mitotic spindle is critical to the
      fidelity of cell division. Mitotic precision fundamentally contributes to cell
      fate specification, tissue development and homeostasis, and chromosome
      distribution within daughter cells. Defects in these events are thought to
      contribute to several human diseases. The underlying mechanisms that function in
      spindle morphogenesis and positioning remain incompletely defined, however. Here
      we describe diverse roles for the actin-microtubule cross-linker Shortstop (Shot)
      in mitotic spindle function in Drosophila Shot localizes to mitotic spindle
      poles, and its knockdown results in an unfocused spindle pole morphology and a
      disruption of proper spindle orientation. Loss of Shot also leads to chromosome
      congression defects, cell cycle progression delay, and defective chromosome
      segregation during anaphase. These mitotic errors trigger apoptosis in Drosophila
      epithelial tissue, and blocking this apoptotic response results in a marked
      induction of the epithelial-mesenchymal transition marker MMP-1. The actin
      binding domain of Shot directly interacts with Actin-related protein-1 (Arp-1), a
      key component of the Dynein/Dynactin complex. Knockdown of Arp-1 phenocopies Shot
      loss universally, whereas chemical disruption of F-actin does so selectively. Our
      work highlights novel roles for Shot in mitosis and suggests a mechanism
      involving Dynein/Dynactin activation.

PMID- 28747440
TI  - Aligned fibers direct collective cell migration to engineer closing and
      nonclosing wound gaps.
AB  - Cell emergence onto damaged or organized fibrous extracellular matrix (ECM) is a
      crucial precursor to collective cell migration in wound closure and cancer
      metastasis, respectively. However, there is a fundamental gap in our quantitative
      understanding of the role of local ECM size and arrangement in cell emergence
      based migration and local gap closure. Here, using ECM-mimicking nanofibers
      bridging cell monolayers, we describe a method to recapitulate and quantitatively
      describe these in vivo behaviors over multispatial (single cell to cell sheets)
      and temporal (minutes to weeks) scales. On fiber arrays with large interfiber
      spacing, cells emerge (invade) either singularly by breaking cell-cell junctions
      analogous to release of a stretched rubber band (recoil), or in groups of few
      cells (chains), whereas on closely spaced fibers, multiple chains emerge
      collectively. Advancing cells on fibers form cell streams, which support
      suspended cell sheets (SCS) of various sizes and curvatures. SCS converge to form
      local gaps that close based on both the gap size and shape. We document that cell
      stream spacing of 375 um and larger hinders SCS advancement, thus providing
      abilities to engineer closing and nonclosing gaps. Altogether we highlight the
      importance of studying cell-fiber interactions and matrix structural remodeling
      in fundamental and translational cell biology.

PMID- 28747441
TI  - Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds:
      A meta-analysis.
AB  - OBJECTIVE: We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH
      survivors, stratified by the presence, distribution, and number of cerebral
      microbleeds (CMBs) on MRI (i.e., the presumed causal underlying small vessel
      disease and its severity). METHODS: This was a meta-analysis of prospective
      cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We
      estimated annualized recurrent symptomatic ICH rates for each study and compared
      pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed
      etiology based on CMB distribution (strictly lobar CMBs related to probable or
      possible cerebral amyloid angiopathy [CAA] vs non-CAA) and burden (1, 2-4, 5-10,
      and >10 CMBs), using random effects models. RESULTS: We pooled data from 10
      studies including 1,306 patients: 325 with CAA-related and 981 CAA-unrelated ICH.
      The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH
      (7.4%, 95% confidence interval [CI] 3.2-12.6 vs 1.1%, 95% CI 0.5-1.7 per year,
      respectively; p = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none)
      were associated with ICH recurrence during follow-up (range 1-3 years): OR 3.1
      (95% CI 1.4-6.8; p = 0.006), 4.3 (95% CI 1.8-10.3; p = 0.001), and 3.4 (95% CI
      1.4-8.3; p = 0.007) for 2-4, 5-10, and >10 CMBs, respectively. In CAA-unrelated
      ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95%
      CI 2.1-15; p = 0.001). The presence of 1 CMB (versus none) was not associated
      with recurrent ICH in CAA-related or CAA-unrelated cohorts. CONCLUSIONS: CMB
      burden and distribution on MRI identify subgroups of ICH survivors with higher
      ICH recurrence risk, which may help to predict ICH prognosis with relevance for
      clinical practice and treatment trials.

PMID- 28747442
TI  - Chemotherapy-induced peripheral neuropathy clinical trials: Review and
      recommendations.
AB  - OBJECTIVE: To assess the design characteristics and reporting quality of
      published randomized controlled trials (RCTs) for treatments of chemotherapy
      induced peripheral neuropathy (CIPN) initiated before or during chemotherapy.
      METHODS: In this systematic review of RCTs of preventive or symptomatic
      pharmacologic treatments for CIPN initiated before or during chemotherapy
      treatment, articles were identified by updating the PubMed search utilized in the
      CIPN treatment guidelines published in the Journal of Clinical Oncology in 2014.
      RESULTS: Thirty-eight articles were identified. The majority included only
      patients receiving platinum therapies (61%) and used a placebo control (79%).
      Common exclusion criteria were preexisting neuropathy (84%), diabetes (55%), and
      receiving treatments that could potentially improve neuropathy symptoms (45%).
      Ninety-five percent of studies initiated the experimental treatment before CIPN
      symptoms occurred. Although 58% of articles identified a primary outcome measure
      (POM), only 32% specified a primary analysis. Approximately half (54%) of the
      POMs were patient-reported outcome measures of symptoms and functional
      impairment. Other POMs included composite measures of symptoms and clinician
      rated signs (23%) and vibration tests (14%). Only 32% of articles indicated how
      data from participants who prematurely discontinued chemotherapy were analyzed,
      and 21% and 29% reported the number of participants who discontinued chemotherapy
      due to neuropathy or other/unspecified reasons, respectively. CONCLUSIONS: These
      data identify reporting practices that could be improved in order to enhance
      readers' ability to critically evaluate RCTs of CIPN treatments and use the
      findings to inform the design of future studies and clinical practice. Reporting
      recommendations are provided.

PMID- 28747443
TI  - Thiamine-responsive disease due to mutation of tpk1: Importance of avoiding
      misdiagnosis.

PMID- 28747445
TI  - Recurrent ictal asystole: Are we doing enough to prevent and treat it?

PMID- 28747444
TI  - Recurrence risk of ictal asystole in epilepsy.
AB  - OBJECTIVE: To determine the recurrence risk of ictal asystole (IA) and its
      determining factors in people with epilepsy. METHODS: We performed a systematic
      review of published cases with IA in 3 databases and additionally searched our
      local database for patients with multiple seizures simultaneously recorded with
      ECG and EEG and at least one IA. IA recurrence risk was estimated by including
      all seizures without knowledge of the chronological order. Various clinical
      features were assessed by an individual patient data meta-analysis. A random
      mixed effect logistic regression model was applied to estimate the average
      recurrence risk of IA. Plausibility of the calculated IA recurrence risk was
      checked by analyzing the local dataset with available information in
      chronological order. RESULTS: Eighty patients with 182 IA in 537 seizures were
      included. Recurrence risk of IA amounted to 40% (95% confidence interval [CI] 32%
      50%). None of the clinical factors (age, sex, type and duration of epilepsy,
      hemispheric lateralization, duration of IA per patient) appeared to have a
      significant effect on the short-term recurrence risk of IA. When considering the
      local dataset only, IA recurrence risk was estimated to 30% (95% CI 14%-53%).
      Information whether IA coincided with symptoms (i.e., syncope) or not was given
      in 60 patients: 100 out of 142 IAs were symptomatic. CONCLUSION: Our data suggest
      that in case of clinically suspected IA, the recording of 1 or 2 seizures is not
      sufficient to rule out IA. Furthermore, the high short-term recurrence risk
      favors aggressive treatment, including pacemaker implantation if seizure freedom
      cannot be achieved.

PMID- 28747446
TI  - Transcranial magnetic stimulation distinguishes Alzheimer disease from
      frontotemporal dementia.
AB  - OBJECTIVE: To determine whether a transcranial magnetic stimulation (TMS)
      multiparadigm approach can be used to distinguish Alzheimer disease (AD) from
      frontotemporal dementia (FTD). METHODS: Paired-pulse TMS was used to investigate
      short-interval intracortical inhibition (SICI) and facilitation (ICF), long
      interval intracortical inhibition, and short-latency afferent inhibition (SAI) to
      measure the activity of different intracortical circuits in patients with AD,
      patients with FTD, and healthy controls (HC). The primary outcome measures were
      sensitivity and specificity of TMS measures, derived from receiver operating
      curve analysis. RESULTS: A total of 175 participants met the inclusion criteria.
      We diagnosed 79 patients with AD, 64 patients with FTD, and 32 HC. We found that
      while patients with AD are characterized by a specific impairment of SAI, FTD
      shows a remarkable dysfunction of SICI-ICF intracortical circuits. With the use
      of the best indexes, TMS differentiated FTD from AD with a sensitivity of 91.8%
      and specificity of 88.6%, AD from HC with a sensitivity of 84.8% and specificity
      of 90.6%, and FTD from HC with a sensitivity of 90.2% and specificity of 78.1%.
      These results were confirmed in patients with mild disease. CONCLUSIONS: TMS is a
      noninvasive procedure that reliably distinguishes AD from FTD and HC and, if
      these findings are replicated in larger studies, could represent a useful
      additional diagnostic tool for clinical practice. CLASSIFICATION OF EVIDENCE:
      This study provides Class III evidence that TMS measures can distinguish patients
      with AD from those with FTD.

PMID- 28747447
TI  - Long-term AIDS-related PCNSL outcomes with HD-MTX and combined antiretroviral
      therapy.
AB  - OBJECTIVE: To assess the characteristics and outcomes of patients with AIDS
      related primary CNS lymphoma (AR-PCNSL) in the combined antiretroviral therapy
      (cART) era systematically treated with high-dose methotrexate (HD-MTX). METHODS:
      We retrospectively analyzed (intention-to-treat analysis) 51 consecutive patients
      with AR-PCNSL (median age 39 years) who were diagnosed from 1996 to 2014 and
      treated with a median of 6 (range 1-15) infusions of HD-MTX (3 g/m2) combined
      with cART. RESULTS: Median all-patients' and survivors' follow-up lasted 23
      (range 0-186) and 76 (range 23-186) months, respectively. At PCNSL diagnosis, 83%
      of the patients were on cART, median plasma HIV load was 175,600 copies/mL, and
      median CD4+ T-cell count was 24/MUL. Median Eastern Cooperative Oncology Group
      performance status was 2 (range 1-4). Median overall survival (OS) was 5.7 years,
      with 5- and 10-year rates of 48% and 41%. Median time to progression was not
      reached (69% at 10 months). PCNSL was the direct cause of 14 deaths, all observed
      within the 10 months after its diagnosis: 6 patients died before HD-MTX could be
      administered, 4 had refractory disease, and 4 relapsed. Multivariate analyses
      retained time interval between AIDS diagnosis and PCNSL diagnosis, age at AR
      PCNSL diagnosis, and deep brain structure involvement as independent OS
      predictive factors. To restore effective immune function, cART tailored to HIV
      genotypes was started and combined with HD-MTX; no interactions and no immune
      reconstitution inflammatory syndrome occurred. No patient died of acute treatment
      related toxicity, and 21 of 51 (41%) patients experienced grade 3/4 toxicity.
      CONCLUSIONS: Combined short-term HD-MTX monochemotherapy and optimal cART simply
      and effectively treat AR-PCNSL, achieving long-term survival with few relapses.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that short-term
      HD-MTX monochemotherapy improves long-term survival of patients with AIDS with
      primary CNS lymphoma receiving cARTs.

PMID- 28747448
TI  - Movement disorder in GNAO1 encephalopathy associated with gain-of-function
      mutations.
AB  - OBJECTIVE: To define molecular mechanisms underlying the clinical spectrum of
      epilepsy and movement disorder in individuals with de novo mutations in the GNAO1
      gene. METHODS: We identified all GNAO1 mutations reported in individuals with
      epilepsy (early infantile epileptiform encephalopathy 17) or movement disorders
      through April 2016; 15 de novo mutant alleles from 25 individuals were introduced
      into the Galphao subunit by site-directed mutagenesis in a mammalian expression
      plasmid. We assessed protein expression and function in vitro in HEK-293T cells
      by Western blot and determined functional Galphao-dependent cyclic adenosine
      monophosphate (cAMP) inhibition with a coexpressed alpha2A adrenergic receptor.
      RESULTS: Of the 15 clinical GNAO1 mutations studied, 9 show reduced expression
      and loss of function (LOF; <90% maximal inhibition). Six other mutations show
      variable levels of expression but exhibit normal or even gain-of-function (GOF)
      behavior, as demonstrated by significantly lower EC50 values for alpha2A
      adrenergic receptor-mediated inhibition of cAMP. The GNAO1 LOF mutations are
      associated with epileptic encephalopathy while GOF mutants (such as G42R, G203R,
      and E246K) or normally functioning mutants (R209) were found in patients with
      movement disorders with or without seizures. CONCLUSIONS: Both LOF and GOF
      mutations in Galphao (encoded by GNAO1) are associated with neurologic
      pathophysiology. There appears to be a strong predictive correlation between the
      in vitro biochemical phenotype and the clinical pattern of epilepsy vs movement
      disorder.

PMID- 28747449
TI  - Loss of cutaneous large and small fibers in naive and l-dopa-treated PD patients.
AB  - OBJECTIVE: To study small and large fiber pathology in drug-naive and l-dopa
      treated patients affected by Parkinson disease (PD) in early phases, before the
      occurrence of neuropathic electrophysiologic abnormalities. METHODS: We enrolled
      85 patients with idiopathic PD (male/female 49/36, age 61.3 +/- 9.7 years)
      without electrophysiologic signs of neuropathy, including 48 participants naive
      to l-dopa treatment. All patients underwent clinical, functional, and morphologic
      assessment of sensory and autonomic nerves through dedicated questionnaires,
      quantitative sensory testing, sympathetic skin response, dynamic sweat test, and
      punch biopsies from glabrous and hairy skin. Sensory and autonomic innervation
      was visualized with specific antibodies and analyzed by confocal microscopy. Data
      were compared with those obtained from sex- and age-comparable healthy controls.
      In 35 patients, skin biopsies were performed bilaterally to evaluate side-to-side
      differences. RESULTS: Intraepidermal nerve fiber density was lower in patients
      compared to controls in all the examined sites (p < 0.001). The loss was higher
      in the more affected side (p < 0.01). A loss of autonomic nerves to vessels,
      sweat glands, and arrector pili muscles and of Meissner corpuscles and their
      myelinated endings in glabrous skin was found (p < 0.001). Patients showed
      increased tactile and thermal thresholds, impairment of mechanical pain
      perception, and reduced sweat output (p < 0.001). The naive and l-dopa-treated
      groups differed only for Meissner corpuscle density (p < 0.001). CONCLUSIONS:
      Both large and small fiber pathology occurs in the early stages of PD and may
      account for the sensory and autonomic impairment. l-Dopa affects the 2
      populations of fibers differently.

PMID- 28747450
TI  - Magnesium, hemostasis, and outcomes in patients with intracerebral hemorrhage.
AB  - OBJECTIVE: We tested the hypothesis that admission serum magnesium levels are
      associated with hematoma volume, hematoma growth, and functional outcomes in
      patients with intracerebral hemorrhage (ICH). METHODS: Patients presenting with
      spontaneous ICH were enrolled in an observational cohort study that prospectively
      collected demographic, clinical, laboratory, radiographic, and outcome data. We
      performed univariate and adjusted multivariate analyses to assess for
      associations between serum magnesium levels and initial hematoma volume, final
      hematoma volume, and in-hospital hematoma growth as radiographic measures of
      hemostasis, and functional outcome measured by the modified Rankin Scale (mRS) at
      3 months. RESULTS: We included 290 patients for analysis. Admission serum
      magnesium was 2.0 +/- 0.3 mg/dL. Lower admission magnesium levels were associated
      with larger initial hematoma volumes on univariate (p = 0.02), parsimoniously
      adjusted (p = 0.002), and fully adjusted models (p = 0.006), as well as greater
      hematoma growth (p = 0.004, p = 0.005, and p = 0.008, respectively) and larger
      final hematoma volumes (p = 0.02, p = 0.001, and p = 0.002, respectively). Lower
      admission magnesium level was associated with worse functional outcomes at 3
      months (i.e., higher mRS; odds ratio 0.14, 95% confidence interval 0.03-0.64, p =
      0.011) after adjustment for age, admission Glasgow Coma Scale score, initial
      hematoma volume, time from symptom onset to initial CT, and hematoma growth, with
      evidence that the effect of magnesium is mediated through hematoma growth.
      CONCLUSIONS: These data support the hypothesis that magnesium exerts a clinically
      meaningful influence on hemostasis in patients with ICH.

PMID- 28747451
TI  - Epileptic encephalopathy, movement disorder, and the yin and yang of GNAO1
      function.

PMID- 28747452
TI  - MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes.
AB  - OBJECTIVE: To report the 6-month single-blinded results of unilateral thalamotomy
      with MRI-guided focused ultrasound (MRgFUS) in patients with tremors other than
      essential tremor. METHODS: Three patients with tremor due to Parkinson disease, 2
      with dystonic tremor in the context of cervicobrachial dystonia and writer's
      cramp, and 1 with dystonia gene-associated tremor underwent MRgFUS targeting the
      ventro-intermedius nucleus (Vim) of the dominant hemisphere. The primary endpoint
      was the reduction of lateralized items of the Tremor Rating Scale of
      contralateral hemibody assessed by a blinded rater. RESULTS: All patients
      achieved a statistically significant, immediate, and sustained improvement of the
      contralateral tremor score by 42.2%, 52.0%, 55.9%, and 52.9% at 1 week and 1, 3,
      and 6 months after the procedure, respectively. All patients experienced
      transient side effects and 2 patients experienced persistent side effects at the
      time of last evaluation: hemitongue numbness and hemiparesis with
      hemihypoesthesia. CONCLUSIONS: Vim MRgFUS is a promising, incision-free, but
      nevertheless invasive technique to effectively treat tremors other than essential
      tremor. Future studies on larger samples and longer follow-up will further define
      its effectiveness and safety. CLINICALTRIALSGOV IDENTIFIER: NCT02252380.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for
      patients with tremor not caused by essential tremor, MRgFUS of the Vim improves
      the tremor of the contralateral hemibody at 6 months.

PMID- 28747454
TI  - By CyTOF: Heterogeneity of Human Monocytes.

PMID- 28747453
TI  - Serum matrix metalloproteinase-9 levels and prognosis of acute ischemic stroke.
AB  - OBJECTIVE: To examine the association between serum matrix metalloproteinases-9
      (MMP-9) levels and prognosis of acute ischemic stroke. METHODS: We measured serum
      MMP-9 levels in 3,186 participants (2,008 men and 1,178 women) from the China
      Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Study outcome data on
      death, major disability (modified Rankin Scale score >=3), and vascular disease
      were collected at 3 months after stroke onset. RESULTS: During 3 months of follow
      up, 767 participants (24.6%) experienced major disability or died. Serum MMP-9
      was significantly associated with an increased risk of death and major disability
      after adjustment for age, sex, time from onset to randomization, current smoking,
      alcohol drinking, admission NIH Stroke Scale score, diastolic blood pressure,
      plasma glucose, white blood cell counts, use of antihypertensive medications, and
      history of hypertension, coronary heart disease, and diabetes mellitus. For
      example, 1-SD (0.32 ng/mL) higher log-MMP-9 was associated with an odds ratio
      (95% confidence interval) of 1.16 (1.06-1.28) for the combined outcome of death
      and major disability, 1.12 (1.01-1.23) for major disability, and 1.29 (1.01-1.66)
      for death. The addition of serum MMP-9 to conventional risk factors improved risk
      prediction of the combined outcome of death or major disability (net
      reclassification index 9.1%, p = 0.033; integrated discrimination improvement
      0.4%, p = 0.004). CONCLUSIONS: Higher serum MMP-9 levels in the acute phase of
      ischemic stroke were associated with increased risk of mortality and major
      disability, suggesting that serum MMP-9 could be an important prognostic factor
      for ischemic stroke.

PMID- 28747455
TI  - OxPL: Elusive Risk Factor in Calcific Aortic Valve Disease or Another Piece of
      the Puzzle?

PMID- 28747457
TI  - ATVB Named Lecture Review-Insight Into Author: Klaus Ley.

PMID- 28747456
TI  - Do BRD(4)S of a Feather Flock Together? How an Inflammation-Driven Epigenetic
      Regulator May Link Pulmonary Hypertension and Coronary Artery Disease.

PMID- 28747458
TI  - ATVB Named Lecture Review-Insight Into Author: Catherine C. Hedrick.

PMID- 28747459
TI  - Macrophages.

PMID- 28747460
TI  - Carbon Monoxide Preserves Circadian Rhythm to Reduce the Severity of Subarachnoid
      Hemorrhage in Mice.
AB  - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is associated with a
      temporal pattern of stroke incidence. We hypothesized that natural oscillations
      in gene expression controlling circadian rhythm affect the severity of neuronal
      injury. We moreover predict that heme oxygenase-1 (HO-1/Hmox1) and its product
      carbon monoxide (CO) contribute to the restoration of rhythm and neuroprotection.
      METHODS: Murine SAH model was used where blood was injected at various time
      points of the circadian cycle. Readouts included circadian clock gene expression,
      locomotor activity, vasospasm, neuroinflammatory markers, and apoptosis. In
      addition, cerebrospinal fluid and peripheral blood leukocytes from SAH patients
      and controls were analyzed for clock gene expression. RESULTS: Significant
      elevations in the clock genes Per-1, Per-2, and NPAS-2 were observed in the
      hippocampus, cortex, and suprachiasmatic nucleus in mice subjected to SAH at
      zeitgeber time (ZT) 12 when compared with ZT2. Clock gene expression amplitude
      correlated with basal expression of HO-1, which was also significantly greater at
      ZT12. SAH animals showed a significant reduction in cerebral vasospasm, neuronal
      apoptosis, and microglial activation at ZT12 compared with ZT2. In animals with
      myeloid-specific HO-1 deletion (Lyz-Cre-Hmox1fl/fl ), Per-1, Per-2, and NPAS-2
      expression was reduced in the suprachiasmatic nucleus, which correlated with
      increased injury. Treatment with low-dose CO rescued Lyz-Cre-Hmox1fl/fl mice,
      restored Per-1, Per-2, and NPAS-2 expression, and reduced neuronal apoptosis.
      CONCLUSIONS: Clock gene expression regulates, in part, the severity of SAH and
      requires myeloid HO-1 activity to clear the erythrocyte burden and inhibit
      neuronal apoptosis. Exposure to CO rescues the loss of HO-1 and thus merits
      further investigation in patients with SAH.

PMID- 28747461
TI  - Hope Dies Last-Evidence Again Fails to Support a Neuroprotectant: Cerebrolysin
      for Acute Ischemic Stroke.

PMID- 28747462
TI  - Mechanical Thrombectomy Outcomes With and Without Intravenous Thrombolysis in
      Stroke Patients: A Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: Whether prior intravenous thrombolysis provides any
      additional benefits to the patients undergoing mechanical thrombectomy for large
      vessel, acute ischemic stroke remains unclear. METHODS: We conducted a meta
      analysis of 13 studies obtained through PubMed and EMBASE database searches to
      determine whether functional outcome (modified Rankin Scale) at 90 days,
      successful recanalization rate, and symptomatic intracerebral hemorrhage rate
      differed between patients who underwent mechanical thrombectomy with (MT+IVT) and
      without (MT-IVT) pre-treatment with intravenous thrombolysis. RESULTS: MT+IVT
      patients compared with MT-IVT patients had better functional outcomes (modified
      Rankin Scale score, 0-2; summary odds ratio [OR], 1.27 [95% confidence interval
      (CI), 1.05-1.55]; P=0.02; n=1769/1174), lower mortality (OR, 0.71 [95% CI, 0.55
      0.91]; P=0.006; n=1774/1202), and higher rate of successful recanalization (OR,
      1.46 [95% CI, 1.09-1.96]; P=0.01; n=1652/1216) without having increased odds of
      symptomatic intracerebral hemorrhage (OR, 1.11 [95% CI, 0.69-1.77]; P=0.67;
      n=1471/1143). A greater number of MT+IVT patients required <=2 passes with a
      neurothrombectomy device to achieve successful recanalization (OR, 2.06 [95% CI,
      1.37-3.10]; P=0.0005; n=316/231). CONCLUSIONS: Our results demonstrated that
      MT+IVT patients had better functional outcomes, lower mortality, higher rate of
      successful recanalization, requiring lower number of device passes, and equal
      odds of symptomatic intracerebral hemorrhage compared with MT-IVT patients. The
      results support the current guidelines of offering intravenous thrombolysis to
      eligible patients even if they are being considered for mechanical thrombectomy.
      Because the data are compiled from studies where the 2 groups differed based on
      eligibility for intravenous thrombolysis, randomized trials are necessary to
      accurately evaluate the added value of intravenous thrombolysis in patients
      treated with mechanical thrombectomy.

PMID- 28747463
TI  - Impact of Stroke Center Certification on Mortality After Ischemic Stroke: The
      Medicare Cohort From 2009 to 2013.
AB  - BACKGROUND AND PURPOSE: An increasing number of hospitals have been certified as
      primary stroke centers (PSCs). It remains unknown whether the action toward PSC
      certification has improved the outcome of stroke care. This study aimed to
      understand whether PSC certification reduced stroke mortality. METHODS: We
      examined Medicare fee-for-service beneficiaries aged >=65 years who were
      hospitalized between 2009 and 2013 for ischemic stroke. Hospitals were classified
      into 3 groups: new PSCs, the hospitals that received initial PSC certification
      between 2009 and 2013 (n=634); existing PSCs, the PSCs certified before 2009
      (n=785); and non-SCs, the hospitals that have never been certified as PSCs
      (n=2640). Multivariate logistic regression and Cox proportional hazards model was
      used to compare the mortality among the 3 groups. RESULTS: Existing PSCs were
      significantly larger than new PSCs as reflected by total number of beds and
      annual stroke admission (P<0.0001). Compared with existing PSCs, new PSCs had
      lower in-hospital (odds ratio, 0.862; 95% confidence interval [CI], 0.817-0.910)
      and 30-day mortality (hazard ratio [HR], 0.981; 95% CI, 0.968-0.993), after
      adjusting for patient demographics and comorbidities. Compared with non-SCs, new
      PSCs had lower adjusted in-hospital (odds ratio, 0.894; 95% CI, 0.848-0.943), 30
      day (HR, 0.904; 95% CI, 0.892-0.917), and 1-year mortality (HR, 0.907; 95% CI,
      0.898-0.915). Existing PSCs had lower adjusted 30-day (HR, 0.922; 95% CI, 0.911
      0.933) and 1-year mortality (HR, 0.900; 95% CI, 0.892-0.907) than non-SCs.
      CONCLUSIONS: Obtaining stroke certification may reduce stroke mortality and
      overcome the disadvantage of being smaller hospitals. Further study of other
      outcome measures will be useful to improve stroke system of care.

PMID- 28747464
TI  - Lethal digenic mutations in the K+ channels Kir4.1 (KCNJ10) and SLACK (KCNT1)
      associated with severe-disabling seizures and neurodevelopmental delay.
AB  - A 2-yr-old boy presented profound developmental delay, failure to thrive, ataxia,
      hypotonia, and tonic-clonic seizures that caused the death of the patient.
      Targeted and whole exome sequencing revealed two heterozygous missense variants:
      a novel mutation in the KCNJ10 gene that encodes for the inward-rectifying K+
      channel Kir4.1 and another previously characterized mutation in KCNT1 that
      encodes for the Na+-activated K+ channel known as Slo2.2 or SLACK. The objectives
      of this study were to perform the clinical and genetic characterization of the
      proband and his family and to examine the functional consequence of the Kir4.1
      mutation. The mutant and wild-type KCNJ10 constructs were generated and
      heterologously expressed in Xenopus laevis oocytes, and whole cell K+ currents
      were measured using the two-electrode voltage-clamp technique. The KCNJ10
      mutation c.652C>T resulted in a p.L218F substitution at a highly conserved
      residue site. Wild-type KCNJ10 expression yielded robust Kir current, whereas
      currents from oocytes expressing the mutation were reduced, remarkably. Western
      Blot analysis revealed reduced protein expression by the mutation. Kir5.1
      subunits display selective heteromultimerization with Kir4.1 constituting
      channels with unique kinetics. The effect of the mutation on Kir4.1/5.1 channel
      activity was twofold: a reduction in current amplitudes and an increase in the pH
      dependent inhibition. We thus report a novel loss-of-function mutation in Kir4.1
      found in a patient with a coexisting mutation in SLACK channels that results in a
      fatal disease.NEW & NOTEWORTHY We present and characterize a novel mutation in
      KCNJ10 Unlike previously reported EAST/SeSAME patients, our patient was
      heterozygous, and contrary to previous studies, mimicking the heterozygous state
      by coexpression resulted in loss of channel function. We report in the same
      patient co-occurrence of a KCNT1 mutation resulting in a more severe phenotype.
      This study provides new insights into the phenotypic spectrum and to the genotype
      phenotype correlations associated with EAST/SeSAME and MMFSI.

PMID- 28747465
TI  - Unbounded evidence accumulation characterizes subjective visual vertical forced
      choice perceptual choice and confidence.
AB  - Humans can subjectively yet quantitatively assess choice confidence based on
      perceptual precision even when a perceptual decision is made without an immediate
      reward or feedback. However, surprisingly little is known about choice
      confidence. Here we investigate the dynamics of choice confidence by merging two
      parallel conceptual frameworks of decision making, signal detection theory and
      sequential analyses (i.e., drift-diffusion modeling). Specifically, to capture
      end-point statistics of binary choice and confidence, we built on a previous
      study that defined choice confidence in terms of psychophysics derived from
      signal detection theory. At the same time, we augmented this mathematical model
      to include accumulator dynamics of a drift-diffusion model to characterize the
      time dependence of the choice behaviors in a standard forced-choice paradigm in
      which stimulus duration is controlled by the operator. Human subjects performed a
      subjective visual vertical task, simultaneously reporting binary orientation
      choice and probabilistic confidence. Both binary choice and confidence
      experimental data displayed statistics and dynamics consistent with both signal
      detection theory and evidence accumulation, respectively. Specifically, the
      computational simulations showed that the unbounded evidence accumulator model
      fits the confidence data better than the classical bounded model, while bounded
      and unbounded models were indistinguishable for binary choice data. These results
      suggest that the brain can utilize mechanisms consistent with signal detection
      theory-especially when judging confidence without time pressure.NEW & NOTEWORTHY
      We found that choice confidence data show dynamics consistent with evidence
      accumulation for a forced-choice subjective visual vertical task. We also found
      that the evidence accumulation appeared unbounded when judging confidence, which
      suggests that the brain utilizes mechanisms consistent with signal detection
      theory to determine choice confidence.

PMID- 28747466
TI  - Network activity influences the subthreshold and spiking visual responses of
      pyramidal neurons in the three-layer turtle cortex.
AB  - A primary goal of systems neuroscience is to understand cortical function,
      typically by studying spontaneous and stimulus-modulated cortical activity.
      Mounting evidence suggests a strong and complex relationship exists between the
      ongoing and stimulus-modulated cortical state. To date, most work in this area
      has been based on spiking in populations of neurons. While advantageous in many
      respects, this approach is limited in scope: it records the activity of a
      minority of neurons and gives no direct indication of the underlying subthreshold
      dynamics. Membrane potential recordings can fill these gaps in our understanding,
      but stable recordings are difficult to obtain in vivo. Here, we recorded
      subthreshold cortical visual responses in the ex vivo turtle eye-attached whole
      brain preparation, which is ideally suited for such a study. We found that, in
      the absence of visual stimulation, the network was "synchronous"; neurons
      displayed network-mediated transitions between hyperpolarized (Down) and
      depolarized (Up) membrane potential states. The prevalence of these slow-wave
      transitions varied across turtles and recording sessions. Visual stimulation
      evoked similar Up states, which were on average larger and less reliable when the
      ongoing state was more synchronous. Responses were muted when immediately
      preceded by large, spontaneous Up states. Evoked spiking was sparse, highly
      variable across trials, and mediated by concerted synaptic inputs that were, in
      general, only very weakly correlated with inputs to nearby neurons. Together,
      these results highlight the multiplexed influence of the cortical network on the
      spontaneous and sensory-evoked activity of individual cortical neurons.NEW &
      NOTEWORTHY Most studies of cortical activity focus on spikes. Subthreshold
      membrane potential recordings can provide complementary insight, but stable
      recordings are difficult to obtain in vivo. Here, we recorded the membrane
      potentials of cortical neurons during ongoing and visually evoked activity. We
      observed a strong relationship between network and single-neuron evoked activity
      spanning multiple temporal scales. The membrane potential perspective of cortical
      dynamics thus highlights the influence of intrinsic network properties on visual
      processing.

PMID- 28747467
TI  - Isoflurane, ketamine-xylazine, and urethane markedly alter breathing even at
      subtherapeutic doses.
AB  - Anesthetics are widely used for animal research on respiratory control in vivo,
      but their effect on breathing and CO2 chemoreception has not been well
      characterized in mice, a species now often used for these studies. We previously
      demonstrated that 1% isoflurane markedly reduces the hypercapnic ventilatory
      response (HCVR) in adult mice in vivo and masks serotonin [5-hydroxytryptamine (5
      HT)] neuron chemosensitivity in vitro. Here we investigated effects of 0.5%
      isoflurane on breathing in adult mice and also found a large reduction in the
      HCVR even at this subanesthetic concentration. We then tested the effects on
      breathing of ketamine-xylazine and urethane, anesthetics widely used in research
      on breathing. We found that these agents altered baseline breathing and blunted
      the HCVR at doses within the range typically used experimentally. At lower doses
      ventilation was decreased, but mice appropriately matched their ventilation to
      metabolic demands due to a parallel decrease in O2 consumption. Neither ketamine
      nor urethane decreased chemosensitivity of 5-HT neurons. These results indicate
      that baseline breathing and/or CO2 chemoreception in mice are decreased by
      anesthetics widely viewed as not affecting respiratory control, and even at
      subtherapeutic doses. These effects of anesthetics on breathing may alter the
      interpretation of studies of respiratory physiology in vivo.NEW & NOTEWORTHY
      Anesthetics are frequently used in animal research, but their effects on
      physiological functions in mice have not been well defined. Here we investigated
      the effects of commonly used anesthetics on breathing in mice. We found that all
      tested anesthetics significantly reduced the hypercapnic ventilatory response
      (HCVR), even at subtherapeutic doses. In addition, ketamine-xylazine and urethane
      anesthesia altered baseline breathing. These data indicate that breathing and the
      HCVR in mice are highly sensitive to anesthetic modulation.

PMID- 28747468
TI  - Sympathetic neural and hemodynamic responses to head-up tilt during isoosmotic
      and hyperosmotic hypovolemia.
AB  - We hypothesized that muscle sympathetic nerve activity (MSNA) during head-up tilt
      (HUT) would be augmented during exercise-induced (hyperosmotic) dehydration but
      not isoosmotic dehydration via an oral diuretic. We studied 26 young healthy
      subjects (7 female, 19 male) divided into three groups: euhydrated (EUH, n = 7),
      previously exercised in 40 degrees C while maintaining hydration; dehydrated
      (DEH, n = 10), previously exercised in 40 degrees C during which ~3% of body
      weight was lost via sweat loss; and diuretic (DIUR, n = 9), a group that did not
      exercise but lost ~3% of body weight via diuresis (furosemide, 80 mg by mouth).
      We measured MSNA, heart rate (HR), and blood pressure (BP) during supine rest and
      30 degrees  and 45 degrees  HUT. Plasma volume (PV) decreased similarly in DEH (
      8.5 +/- 3.3%) and DIUR (-11.4 +/- 5.7%) (P > 0.05). Plasma osmolality was similar
      between DIUR and EUH (288 +/- 4 vs. 284 +/- 5 mmol/kg, respectively) but was
      significantly higher in DEH (299 +/- 5 mmol/kg) (P < 0.05). Mixed-model ANOVA was
      used with repeated measures on position (HUT) and between-group analysis on
      condition. HR and MSNA increased in all subjects during HUT (main effect of
      position; P < 0.05). There was also a significant main effect of group, such that
      MSNA and HR were higher in DEH compared with DIUR (P < 0.05). Changes in HR with
      HUT were larger in both hypovolemic groups compared with EUH (P < 0.05). The
      differential HUT response "strategies" in each group suggest a greater role for
      hypovolemia per se in controlling HR responses during dehydration, and a stronger
      role for osmolality in control of SNA.NEW & NOTEWORTHY Interactions of volume
      regulation with control of vascular sympathetic nerve activity (SNA) have
      important implications for blood pressure regulation. Here, we demonstrate that
      SNA and heart rate (HR) during hyperosmotic hypovolemia (exercise-induced) were
      augmented during supine and tilt compared with isoosmotic hypovolemia (diuretic),
      which primarily augmented the HR response. Our data suggest that hypovolemia per
      se had a larger role in controlling HR responses, whereas osmolality had a
      stronger role in control of SNA.

PMID- 28747469
TI  - alpha-Motoneurons maintain biophysical heterogeneity in obesity and diabetes in
      Zucker rats.
AB  - Small-diameter sensory dysfunction resulting from diabetes has received much
      attention in the literature, whereas the impact of diabetes on alpha-motoneurons
      (MN) has not. In addition, the chance of developing insulin resistance and
      diabetes is increased in obesity. No study has examined the impact of obesity or
      diabetes on the biophysical properties of MN. Lean Zucker rats and Zucker
      diabetic fatty (ZDF) rats were separated into lean, obese (ZDF fed standard
      chow), and diabetic (ZDF fed high-fat diet that led to diabetes) groups. Glass
      micropipettes recorded hindlimb MN properties from identified flexor and extensor
      MN. MN were separated within their groups on the basis of input conductance,
      which created high- and low-input conductance subpopulations for each. A
      significant shorter (20%) afterhyperpolarization half-decay (AHP1/2) was found in
      low-conductance MN for the diabetic group only, whereas AHP1/2 tended to be
      shorter in the obese group (19%). Significant positive correlations were found
      among rheobase and input conductance for both lean and obese animals. No
      differences were found between the groups for afterhyperpolarization amplitude
      (AHPamp), input conductance, rheobase, or any of the rhythmic firing properties
      (frequency-current slope and spike-frequency adaptation index). MN properties
      continue to be heterogeneous in obese and diabetic animals. Obesity does not seem
      to influence lumbar MN. Despite the resistance of MN to the impact of diabetes,
      the reduced AHP1/2 decay and the tendency for a reduction in AHPamp may be the
      first sign of change to MN function.NEW & NOTEWORTHY Knowledge about the impact
      of obesity and diabetes on the biophysical properties of motoneurons is lacking.
      We found that diabetes reduces the duration of the afterhyperpolarization and
      that motoneuron function is unchanged by obesity. A reduced
      afterhyperpolarization may impact discharge characteristics and may be the first
      sign of change to motoneuron function.

PMID- 28747470
TI  - The third-stimulus temporal discrimination threshold: focusing on the temporal
      processing of sensory input within primary somatosensory cortex.
AB  - The somatosensory temporal discrimination threshold (STDT) has been used in
      recent years to investigate time processing of sensory information, but little is
      known about the physiological correlates of somatosensory temporal
      discrimination. The objective of this study was to investigate whether the time
      interval required to discriminate between two stimuli varies according to the
      number of stimuli in the task. We used the third-stimulus temporal discrimination
      threshold (ThirdDT), defined as the shortest time interval at which an individual
      distinguishes a third stimulus following a pair of stimuli delivered at the STDT.
      The STDT and ThirdDT were assessed in 31 healthy subjects. In a subgroup of 10
      subjects, we evaluated the effects of the stimuli intensity on the ThirdDT. In a
      subgroup of 16 subjects, we evaluated the effects of S1 continuous theta-burst
      stimulation (S1-cTBS) on the STDT and ThirdDT. Results show that ThirdDT is
      shorter than STDT. We found a positive correlation between STDT and ThirdDT
      values. As long as the stimulus intensity was within the perceivable and painless
      range, it did not affect ThirdDT values. S1-cTBS significantly affected both STDT
      and ThirdDT, although the latter was affected to a greater extent and for a
      longer period of time. We conclude that the interval needed to discriminate
      between time-separated tactile stimuli is related to the number of stimuli used
      in the task. STDT and ThirdDT are encoded in S1, probably by a shared tactile
      temporal encoding mechanism whose performance rapidly changes during the
      perception process. ThirdDT is a new method to measure somatosensory temporal
      discrimination.NEW & NOTEWORTHY To investigate whether the time interval required
      to discriminate between stimuli varies according to changes in the stimulation
      pattern, we used the third-stimulus temporal discrimination threshold (ThirdDT).
      We found that the somatosensory temporal discrimination acuity varies according
      to the number of stimuli in the task. The ThirdDT is a new method to measure
      somatosensory temporal discrimination and a possible index of inhibitory activity
      at the S1 level.

PMID- 28747471
TI  - Co-option of a motor-to-sensory histaminergic circuit correlates with insect
      flight biomechanics.
AB  - Nervous systems must adapt to shifts in behavioural ecology. One form of
      adaptation is neural exaptation, in which neural circuits are co-opted to perform
      additional novel functions. Here, we describe the co-option of a motor-to
      somatosensory circuit into an olfactory network. Many moths beat their wings
      during odour-tracking, whether walking or flying, causing strong oscillations of
      airflow around the antennae, altering odour plume structure. This self-induced
      sensory stimulation could impose selective pressures that influence neural
      circuit evolution, specifically fostering the emergence of corollary discharge
      circuits. In Manduca sexta, a pair of mesothoracic to deutocerebral histaminergic
      neurons (MDHns), project from the mesothoracic neuromere to both antennal lobes
      (ALs), the first olfactory neuropil. Consistent with a hypothetical role in
      providing the olfactory system with a corollary discharge, we demonstrate that
      the MDHns innervate the ALs of advanced and basal moths, but not butterflies,
      which differ in wing beat and flight pattern. The MDHns probably arose in
      crustaceans and in many arthropods innervate mechanosensory areas, but not the
      olfactory system. The MDHns, therefore, represent an example of architectural
      exaptation, in which neurons that provide motor output information to
      mechanosensory regions have been co-opted to provide information to the olfactory
      system in moths.

PMID- 28747472
TI  - Disentangling sources of variation in SSU rDNA sequences from single cell
      analyses of ciliates: impact of copy number variation and experimental error.
AB  - Small subunit ribosomal DNA (SSU rDNA) is widely used for phylogenetic inference,
      barcoding and other taxonomy-based analyses. Recent studies indicate that SSU
      rDNA of ciliates may have a high level of sequence variation within a single
      cell, which impacts the interpretation of rDNA-based surveys. However, sequence
      variation can come from a variety of sources including experimental errors,
      especially the mutations generated by DNA polymerase in PCR. In the present
      study, we explore the impact of four DNA polymerases on sequence variation and
      find that low-fidelity polymerases exaggerate the estimates of single-cell
      sequence variation. Therefore, using a polymerase with high fidelity is essential
      for surveys of sequence variation. Another source of variation results from
      errors during amplification of SSU rDNA within the polyploidy somatic macronuclei
      of ciliates. To investigate further the impact of SSU rDNA copy number variation,
      we use a high-fidelity polymerase to examine the intra-individual SSU rDNA
      polymorphism in ciliates with varying levels of macronuclear amplification:
      Halteria grandinella, Blepharisma americanum and Strombidium stylifer We estimate
      the rDNA copy numbers of these three species by single-cell quantitative PCR. The
      results indicate that: (i) sequence variation of SSU rDNA within a single cell is
      authentic in ciliates, but the level of intra-individual SSU rDNA polymorphism
      varies greatly among species; (ii) rDNA copy numbers vary greatly among species,
      even those within the same class; (iii) the average rDNA copy number of Halteria
      grandinella is about 567 893 (s.d. = 165 481), which is the highest record of
      rDNA copy number in ciliates to date; and (iv) based on our data and the records
      from previous studies, it is not always true in ciliates that rDNA copy numbers
      are positively correlated with cell or genome size.

PMID- 28747473
TI  - Dissecting the contributions of time and microbe density to variation in immune
      gene expression.
AB  - Widespread differential expression of immunological genes is a hallmark of the
      response to infection in almost all surveyed taxa. However, several challenges
      remain in the attempt to connect differences in gene expression with functional
      outcomes like parasite killing and host survival. For example, temporal gene
      expression patterns are not always monotonic (unidirectional slope), yielding
      results that qualitatively depend on the time point selected for analysis. They
      may also be correlated to microbe density, confounding the strength of an immune
      response and resistance to parasites. In this study, we analyse these
      relationships in an mRNA-seq time series of Tribolium castaneum infected with
      Bacillus thuringiensis Our results suggest that many extracellular immunological
      components with known roles in immunity, like antimicrobial peptides and
      recognition proteins, are highly correlated to microbe load. On the other hand,
      intracellular components of immunological signalling pathways overwhelmingly show
      non-monotonic temporal patterns of gene expression, despite the underlying
      assumption of monotonicity in most ecological and comparative transcriptomics
      studies that rely on cross-sectional analyses. Our results raise a host of new
      questions, including to what extent variation in host resistance, infection
      tolerance and immunopathology can be explained by variation in the slope or
      sensitivity of these newly characterized patterns.

PMID- 28747474
TI  - Male-female relatedness at specific SNP-linkage groups influences cryptic female
      choice in Chinook salmon (Oncorhynchus tshawytscha).
AB  - In a range of taxa, the relatedness between mates influences both pre- and post
      mating processes of sexual selection. However, relatively little is known about
      the genetic loci facilitating such a bias, with the exception of the major
      histocompatibility complex. Here, we performed tightly controlled replicated in
      vitro fertilization trials to explore the impact of relatedness on two possible
      mechanisms of cryptic female choice (CFC) in Chinook salmon (Oncorhynchus
      tshawytscha). We tested (i) whether relatedness of mates, assessed using 682
      single nucleotide polymorphisms (SNPs) on 29 SNP-linkage groups (LGs), biases a
      male's sperm velocity in ovarian fluid (a parameter previously shown to predict
      male fertilization success), and (ii) whether relatedness of mates governs
      fertilization success via other mechanisms, probably via sperm-egg interactions.
      We found that relatedness on three LGs explained the variation in sperm velocity,
      and relatedness on two LGs explained fertilization success, which might indicate
      the presence of genes important in sperm-ovarian fluid and sperm-egg interactions
      in these genomic regions. Mapping of the SNPs on these LGs to the rainbow trout
      genome revealed two genes that affect fertility in humans and represent candidate
      genes for further studies. Our results thereby provide a novel contribution to
      the understanding of the mechanism of CFC.

PMID- 28747475
TI  - Daphniid zooplankton assemblage shifts in response to eutrophication and metal
      contamination during the Anthropocene.
AB  - Human activities during the Anthropocene result in habitat degradation that has
      been associated with biodiversity loss and taxonomic homogenization of ecological
      communities. Here we estimated effects of eutrophication and heavy metal
      contamination, separately and in combination, in explaining zooplankton species
      composition during the past 125-145 years using analysis of daphniid diapausing
      egg banks from four lakes in the northeastern USA. We then examined how these
      community shifts influenced patterns of diversity and homogenization. Analysis of
      past lake production (via subfossil pigments) and metal contamination (via
      sedimentary metals) demonstrated that eutrophication alone (19-39%) and in
      combination with metal pollution (17-54%) explained 36-79% of historical
      variation in daphniid species relative abundances in heavily fertilized lakes. In
      contrast, metal pollution alone explained the majority (72%) of historical
      variation in daphniid assemblages at the oligotrophic site. Several species
      colonization events in eutrophying lakes resulted in increased species richness
      and gamma diversity through time. At the same time, daphniid assemblages in three
      eutrophied lakes became more similar to each other (homogenized), but this
      pattern was only seen when accounting for species presence/absence. We did not
      observe consistent patterns of divergence between the assemblages in the
      eutrophying lakes and the low-nutrient reference site. Given the pervasive nature
      of fertilization and metal pollution, and the sensitivity of cladocerans to these
      factors, we suggest that many inhabited lake districts may already exhibit
      similar patterns of daphniid assemblage shifts.

PMID- 28747476
TI  - Ancient DNA and morphometric analysis reveal extinction and replacement of New
      Zealand's unique black swans.
AB  - Prehistoric human impacts on megafaunal populations have dramatically reshaped
      ecosystems worldwide. However, the effects of human exploitation on smaller
      species, such as anatids (ducks, geese, and swans) are less clear. In this study
      we apply ancient DNA and osteological approaches to reassess the history of
      Australasia's iconic black swans (Cygnus atratus) including the palaeo-behaviour
      of prehistoric populations. Our study shows that at the time of human
      colonization, New Zealand housed a genetically, morphologically, and potentially
      ecologically distinct swan lineage (C. sumnerensis, Pouwa), divergent from modern
      (Australian) C. atratus Morphological analyses indicate C. sumnerensis exhibited
      classic signs of the 'island rule' effect, being larger, and likely flight
      reduced compared to C. atratus Our research reveals sudden extinction and
      replacement events within this anatid species complex, coinciding with recent
      human colonization of New Zealand. This research highlights the role of
      anthropogenic processes in rapidly reshaping island ecosystems and raises new
      questions for avian conservation, ecosystem re-wilding, and de-extinction.

PMID- 28747477
TI  - Oyster reefs as carbon sources and sinks.
AB  - Carbon burial is increasingly valued as a service provided by threatened
      vegetated coastal habitats. Similarly, shellfish reefs contain significant pools
      of carbon and are globally endangered, yet considerable uncertainty remains
      regarding shellfish reefs' role as sources (+) or sinks (-) of atmospheric CO2
      While CO2 release is a by-product of carbonate shell production (then burial),
      shellfish also facilitate atmospheric-CO2 drawdown via filtration and rapid
      biodeposition of carbon-fixing primary producers. We provide a framework to
      account for the dual burial of inorganic and organic carbon, and demonstrate that
      decade-old experimental reefs on intertidal sandflats were net sources of CO2
      (7.1 +/- 1.2 MgC ha-1 yr-1 (u +/- s.e.)) resulting from predominantly carbonate
      deposition, whereas shallow subtidal reefs (-1.0 +/- 0.4 MgC ha-1 yr-1) and
      saltmarsh-fringing reefs (-1.3 +/- 0.4 MgC ha-1 yr-1) were dominated by organic
      carbon-rich sediments and functioned as net carbon sinks (on par with vegetated
      coastal habitats). These landscape-level differences reflect gradients in
      shellfish growth, survivorship and shell bioerosion. Notably, down-core carbon
      concentrations in 100- to 4000-year-old reefs mirrored experimental-reef data,
      suggesting our results are relevant over centennial to millennial scales,
      although we note that these natural reefs appeared to function as slight carbon
      sources (0.5 +/- 0.3 MgC ha-1 yr-1). Globally, the historical mining of the top
      metre of shellfish reefs may have reintroduced more than 400 000 000 Mg of
      organic carbon into estuaries. Importantly, reef formation and destruction do not
      have reciprocal, counterbalancing impacts on atmospheric CO2 since excavated
      organic material may be remineralized while shell may experience continued
      preservation through reburial. Thus, protection of existing reefs could be
      considered as one component of climate mitigation programmes focused on the
      coastal zone.

PMID- 28747478
TI  - Humans recognize emotional arousal in vocalizations across all classes of
      terrestrial vertebrates: evidence for acoustic universals.
AB  - Writing over a century ago, Darwin hypothesized that vocal expression of emotion
      dates back to our earliest terrestrial ancestors. If this hypothesis is true, we
      should expect to find cross-species acoustic universals in emotional
      vocalizations. Studies suggest that acoustic attributes of aroused vocalizations
      are shared across many mammalian species, and that humans can use these
      attributes to infer emotional content. But do these acoustic attributes extend to
      non-mammalian vertebrates? In this study, we asked human participants to judge
      the emotional content of vocalizations of nine vertebrate species representing
      three different biological classes-Amphibia, Reptilia (non-aves and aves) and
      Mammalia. We found that humans are able to identify higher levels of arousal in
      vocalizations across all species. This result was consistent across different
      language groups (English, German and Mandarin native speakers), suggesting that
      this ability is biologically rooted in humans. Our findings indicate that humans
      use multiple acoustic parameters to infer relative arousal in vocalizations for
      each species, but mainly rely on fundamental frequency and spectral centre of
      gravity to identify higher arousal vocalizations across species. These results
      suggest that fundamental mechanisms of vocal emotional expression are shared
      among vertebrates and could represent a homologous signalling system.

PMID- 28747479
TI  - A nutrient mediates intraspecific competition between rodent malaria parasites in
      vivo.
AB  - Hosts are often infected with multiple strains of a single parasite species.
      Within-host competition between parasite strains can be intense and has
      implications for the evolution of traits that impact patient health, such as drug
      resistance and virulence. Yet the mechanistic basis of within-host competition is
      poorly understood. Here, we demonstrate that a parasite nutrient, para
      aminobenzoic acid (pABA), mediates competition between a drug resistant and drug
      susceptible strain of the malaria parasite, Plasmodium chabaudi We further show
      that increasing pABA supply to hosts infected with the resistant strain worsens
      disease and changes the relationship between parasite burden and pathology. Our
      experiments demonstrate that, even when there is profound top-down regulation
      (immunity), bottom-up regulation of pathogen populations can occur and that its
      importance may vary during an infection. The identification of resources that can
      be experimentally controlled opens up the opportunity to manipulate competitive
      interactions between parasites and hence their evolution.

PMID- 28747480
TI  - Effects of age and reproductive status on individual foraging site fidelity in a
      long-lived marine predator.
AB  - Individual foraging specializations, where individuals use a small component of
      the population niche width, are widespread in nature with important ecological
      and evolutionary implications. In long-lived animals, foraging ability develops
      with age, but we know little about the ontogeny of individuality in foraging.
      Here we use precision global positioning system (GPS) loggers to examine how
      individual foraging site fidelity (IFSF), a common component of foraging
      specialization, varies between breeders, failed breeders and immatures in a long
      lived marine predator-the northern gannet Morus bassanus Breeders (aged 5+)
      showed strong IFSF: they had similar routes and were faithful to distal points
      during successive trips. However, centrally placed immatures (aged 2-3) were far
      more exploratory and lacked route or foraging site fidelity. Failed breeders were
      intermediate: some with strong fidelity, others being more exploratory.
      Individual foraging specializations were previously thought to arise as a
      function of heritable phenotypic differences or via social transmission. Our
      results instead suggest a third alternative-in long-lived species foraging sites
      are learned during exploratory behaviours early in life, which become canalized
      with age and experience, and refined where possible-the exploration-refinement
      foraging hypothesis. We speculate similar patterns may be present in other long
      lived species and moreover that long periods of immaturity may be a consequence
      of such memory-based individual foraging strategies.

PMID- 28747481
TI  - Adaptation to public goods cheats in Pseudomonas aeruginosa.
AB  - Cooperation in nature is ubiquitous, but is susceptible to social cheats who pay
      little or no cost of cooperation yet reap the benefits. The effect such cheats
      have on reducing population productivity suggests that there is selection for
      cooperators to mitigate the adverse effects of cheats. While mechanisms have been
      elucidated for scenarios involving a direct association between producer and
      cooperative product, it is less clear how cooperators may suppress cheating in an
      anonymous public goods scenario, where cheats cannot be directly identified.
      Here, we investigate the real-time evolutionary response of cooperators to cheats
      when cooperation is mediated by a diffusible public good: the production of iron
      scavenging siderophores by Pseudomonas aeruginosa We find that siderophore
      producers evolved in the presence of a high frequency of non-producing cheats
      were fitter in the presence of cheats, at no obvious cost to population
      productivity. A novel morphotype independently evolved and reached higher
      frequencies in cheat-adapted versus control populations, exhibiting reduced
      siderophore production but increased production of pyocyanin-an extracellular
      toxin that can also increase the availability of soluble iron. This suggests that
      cooperators may have mitigated the negative effects of cheats by downregulating
      siderophore production and upregulating an alternative iron-acquisition public
      good. More generally, the study emphasizes that cooperating organisms can rapidly
      adapt to the presence of anonymous cheats without necessarily incurring fitness
      costs in the environment they evolve in.

PMID- 28747482
TI  - Pale and dark morphs of tawny owls show different patterns of telomere dynamics
      in relation to disease status.
AB  - Parasites are expected to exert long-term costs on host fecundity and longevity.
      Understanding the consequences of heritable polymorphic variation in disease
      defence in wild populations is essential in order to predict evolutionary
      responses to changes in disease risk. Telomeres have been found to shorten faster
      in malaria-diseased individuals compared with healthy ones with negative effects
      on longevity and thereby fitness. Here, we study the impact of haemosporidian
      blood parasites on telomere dynamics in tawny owls, which display a highly
      heritable plumage colour polymorphism. Previously, it has been shown that blood
      parasites have morph-specific impact on body mass maintenance. Here, we show that
      telomeres shortened faster in individuals with shorter breeding lifespan.
      Telomere length was negatively associated with the degree of pheomelanic brown
      coloration and shorter in infected than uninfected individuals. The rate of
      telomere shortening between breeding seasons was faster in darker pheomelanic
      individuals and suppression of parasite intensity between seasons was associated
      with faster telomere shortening in the paler individuals but not in darker ones.
      We propose that morph-specific physiological profiles cause differential telomere
      shortening and that this is likely to be a mechanism involved in previously
      documented environment-driven survival selection against the pheomelanic morph in
      this population.

PMID- 28747483
TI  - Multi-functional roles of a soldier-specific volatile as a worker arrestant,
      primer pheromone and an antimicrobial agent in a termite.
AB  - Division of labour in eusocial insects is characterized by efficient
      communication systems based on pheromones. Among such insects, termites have
      evolved specialized sterile defenders, called soldiers. Because they are
      incapable of feeding themselves, it has been suggested that soldiers are
      sustained by workers and emit the pheromone arresting workers. However, such a
      soldier pheromone has not been identified in any termite species, and the details
      of the soldier-worker interaction remain to be explored. Here, we identified a
      soldier-specific volatile sesquiterpene as a worker arrestant, which also acts as
      a primer pheromone regulating soldier differentiation and fungistatic agent in a
      termite Reticulitermes speratus Chemical analyses revealed that (-)-beta-elemene
      is the major component of soldier extract, and its authentic standard exhibited
      arrestant activity to workers and inhibited the differentiation from workers to
      soldiers. This compound also showed fungistatic activity against entomopathogenic
      fungi. These suggest that (-)-beta-elemene secreted by soldiers acts not only as
      a worker arrestant but also as one component of inhibitory primer pheromone and
      an anti-pathogenic agent. Our study provides novel evidence supporting the multi
      functionality of termite soldier pheromone and provides new insights into the
      role of soldiers and the evolutionary mechanisms of pheromone compounds.

PMID- 28747484
TI  - A Simple Plasma Retinol Isotope Ratio Method for Estimating beta-Carotene
      Relative Bioefficacy in Humans: Validation with the Use of Model-Based
      Compartmental Analysis.
AB  - Background: Provitamin A carotenoids are an important source of dietary vitamin A
      for many populations. Thus, accurate and simple methods for estimating carotenoid
      bioefficacy are needed to evaluate the vitamin A value of test solutions and
      plant sources. beta-Carotene bioefficacy is often estimated from the ratio of the
      areas under plasma isotope response curves after subjects ingest labeled beta
      carotene and a labeled retinyl acetate reference dose [isotope reference method
      (IRM)], but to our knowledge, the method has not yet been evaluated for
      accuracy.Objectives: Our objectives were to develop and test a physiologically
      based compartmental model that includes both absorptive and postabsorptive beta
      carotene bioconversion and to use the model to evaluate the accuracy of the IRM
      and a simple plasma retinol isotope ratio [(RIR), labeled beta-carotene-derived
      retinol/labeled reference-dose-derived retinol in one plasma sample] for
      estimating relative bioefficacy.Methods: We used model-based compartmental
      analysis (Simulation, Analysis and Modeling software) to develop and apply a
      model that provided known values for beta-carotene bioefficacy. Theoretical data
      for 10 subjects were generated by the model and used to determine bioefficacy by
      RIR and IRM; predictions were compared with known values. We also applied RIR and
      IRM to previously published data.Results: Plasma RIR accurately predicted beta
      carotene relative bioefficacy at 14 d or later. IRM also accurately predicted
      bioefficacy by 14 d, except that, when there was substantial postabsorptive
      bioconversion, IRM underestimated bioefficacy. Based on our model, 1-d
      predictions of relative bioefficacy include absorptive plus a portion of early
      postabsorptive conversion.Conclusion: The plasma RIR is a simple tracer method
      that accurately predicts beta-carotene relative bioefficacy based on analysis of
      one blood sample obtained at >=14 d after co-ingestion of labeled beta-carotene
      and retinyl acetate. The method also provides information about the contributions
      of absorptive and postabsorptive conversion to total bioefficacy if an additional
      sample is taken at 1 d.

PMID- 28747485
TI  - Developmental Vitamin D Deficiency Affects Spatial Learning in Wistar Rats.
AB  - Background: Vitamin D deficiency is a global problem. Recent evidence suggests
      that vitamin D is involved in brain development and function. Vitamin D
      deficiency has been associated with poor cognitive function in adults, but the
      effect of developmental vitamin D deficiency (DVDD) on cognitive function and
      brain development in children has not been well established.Objective: We
      explored the effects of DVDD on cognitive functions and brain morphology of rat
      pups.Methods: Wistar rat pups born to control and vitamin D-deficient dams were
      divided into 4 groups: control (C), deficient during gestation (dG), deficient
      during lactation (dL), and deficient during gestation and lactation (dGL).
      Spatial learning and memory were assessed by the Morris water maze test at
      postnatal day (PND) 24 and PND 45. Cortical thickness at the level of the
      hippocampus was measured at PND 63, and synapses were counted in specified areas
      of the hippocampus at PND 32 and PND 63.Results: Repeated-measures ANOVA revealed
      that at PND 24, learning (escape latency) was impaired (by 42%) in the dGL group,
      whereas at PND 45, both the dL and the dGL groups showed learning impairment (by
      47% and 45%, respectively) compared with their respective C groups (P < 0.05).
      Short-term or long-term memory was largely unaffected by DVDD either at PND 24 or
      PND 45. Compared with the C group, all the DVDD groups had fewer synapses in the
      molecular layer of the hippocampus (P < 0.001). The synapse number decreased by
      54% in the dGL group at PND 33 and by 70% in the dL and dGL groups at PND 63. All
      the DVDD groups at PND 63 showed a reduced cortical thickness (by 22%) compared
      with the C group (P < 0.05).Conclusion: These results suggest that a combined
      prenatal and postnatal DVDD for >=6 wk in rat pups affects learning but not
      memory.

PMID- 28747486
TI  - Modifying the Dietary Carbohydrate-to-Protein Ratio Alters the Postprandial
      Macronutrient Oxidation Pattern in Liver of AMPK-Deficient Mice.
AB  - Background: Hepatic AMP-activated kinase (AMPK) activity is sensitive to the
      dietary carbohydrate-to-protein ratio. However, the role of AMPK in metabolic
      adaptations to variations in dietary macronutrients remains poorly
      understood.Objective: The objective of this study was to determine the role of
      hepatic AMPK in the adaptation of energy metabolism in response to modulation of
      the dietary carbohydrate-to-protein ratio.Methods: Male 7-wk-old wild-type (WT)
      and liver AMPK-deficient (knockout) mice were fed either a normal-protein and
      normal-carbohydrate diet (NP-NC; 14% protein, 76% carbohydrate on an energy
      basis), a low-protein and high-carbohydrate diet (LP-HC; 5% protein, 85%
      carbohydrate), or a high-protein and low-carbohydrate diet (HP-LC; 55% protein,
      35% carbohydrate) for 3 wk. During this period, after an overnight fast,
      metabolic parameters were measured and indirect calorimetry was performed in mice
      during the first hours after refeeding a 1-g calibrated meal of their own diet in
      order to investigate lipid and carbohydrate metabolism.Results: Knockout mice fed
      an LP-HC or HP-LC meal exhibited 24% and 8% lower amplitudes in meal-induced
      carbohydrate and lipid oxidation changes. By contrast, knockout mice fed an NP-NC
      meal displayed normal carbohydrate and lipid oxidation profiles. These mice
      exhibited a transient increase in hepatic triglycerides and a decrease in hepatic
      glycogen. These changes were associated with a 650% higher secretion of
      fibroblast growth factor 21 (FGF21) 2 h after refeeding.Conclusions: The
      consequences of hepatic AMPK deletion depend on the dietary carbohydrate-to
      protein ratio. In mice fed the NP-NC diet, deletion of AMPK in the liver led to
      an adaptation of liver metabolism resulting in increased secretion of FGF21.
      These changes possibly compensated for the absence of hepatic AMPK, as these mice
      exhibited normal postprandial changes in carbohydrate and lipid oxidation. By
      contrast, in mice fed the LP-HC and HP-LC diets, the lack of adjustment in liver
      metabolism in knockout mice resulted in a metabolic inflexibility, leading to a
      reduced amplitude of meal-induced changes in carbohydrate and lipid oxidation.

PMID- 28747487
TI  - Plasma F2-isoprostanes Are Positively Associated with Glycemic Load, but
      Inversely Associated with Dietary Polyunsaturated Fatty Acids and Insoluble Fiber
      in Postmenopausal Women.
AB  - Background: Dietary factors, such as antioxidant nutrients, contribute
      significantly to the maintenance of an appropriate balance between antioxidant
      defense and free radical production in the body.Objective: The objective of this
      study was to examine the relation between oxidative stress as assessed by plasma
      F2-isoprostane (IsoP) concentration, glycemic load (GL), glycemic index (GI),
      intake of antioxidant nutrients, dietary fiber, and polyunsaturated fatty acids
      (PUFAs).Methods: This study was a cross-sectional secondary analysis of baseline
      data collected from a random sample of 269 postmenopausal women participating in
      the Minnesota Green Tea Trial. GL, GI, and dietary variables were calculated from
      the diet history questionnaire. Subjects filled out surveys about the use of anti
      inflammatory drugs and physical activity. Plasma IsoP concentration was assessed
      by GC-mass spectrometry. IsoP concentrations were compared across quartiles of
      GL, GI, insoluble fiber, PUFAs, and antioxidant nutrients with the use of linear
      regression.Results: Antioxidant supplement intake, including zinc, copper,
      vitamin C and vitamin E, was reported by >60% of the participants. Mean intake of
      PUFAs was 12.5 g. Mean plasma IsoP concentrations increased from 34 to 36.7 pg/mL
      in the lowest quartiles of GL and GI, respectively, to 45.2 and 41.6 pg/mL,
      respectively, in the highest quartiles (P-trend = 0.0014 for GL and P-trend =
      0.0379 for GI), whereas mean IsoP concentrations decreased from 41.8 pg/mL in the
      lowest quartile of PUFAs to 34.9 pg/mL in the highest quartile (P-trend =
      0.0416). Similarly, mean IsoP concentrations decreased from 44.4 pg/mL in the
      lowest quartile of insoluble fiber to 36 pg/mL in the highest quartile (P-trend =
      0.0243) after adjustment for potential confounders.Conclusions: We concluded that
      dietary PUFAs and insoluble fiber are inversely associated with oxidative stress
      whereas GL and GI are positively associated with oxidative stress in
      postmenopausal women. This trial was registered at clinicaltrials.gov as
      NCT00917735.

PMID- 28747488
TI  - Should doctors work 24 hour shifts?

PMID- 28747489
TI  - A Novel Selective Inverse Agonist of the CB2 Receptor as a Radiolabeled Tool
      Compound for Kinetic Binding Studies.
AB  - The endocannabinoid system, and in particular the cannabinoid type 2 receptor
      (CB2R), raised the interest of many medicinal chemistry programs for its
      therapeutic relevance in several (patho)physiologic processes. However, the
      physico-chemical properties of tool compounds for CB2R (e.g., the radioligand
      [3H]CP55,940) are not optimal, despite the research efforts in developing
      effective drugs to target this system. At the same time, the importance of drug
      target binding kinetics is growing since the kinetic binding profile of a ligand
      may provide important insights for the resulting in vivo efficacy. In this
      context we synthesized and characterized [3H]RO6957022, a highly selective CB2R
      inverse agonist, as a radiolabeled tool compound. In equilibrium and kinetic
      binding experiments [3H]RO6957022 showed high affinity for human CB2R with fast
      association (kon) and moderate dissociation (koff) kinetics. To demonstrate the
      robustness of [3H]RO6957022 binding, affinity studies were carried out for a wide
      range of CB2R reference ligands, spanning the range of full, partial, and inverse
      agonists. Finally, we used [3H]RO6957022 to study the kinetic binding profiles
      (i.e., kon and koff values) of selected synthetic and endogenous (i.e., 2
      arachidonoylglycerol, anandamide, and noladin ether) CB2R ligands by competition
      association experiments. All tested ligands, and in particular the
      endocannabinoids, displayed distinct kinetic profiles, shedding more light on
      their mechanism of action and the importance of association rates in the
      determination of CB2R affinity. Altogether, this study shows that the use of a
      novel tool compound, i.e., [3H]RO6957022, can support the development of novel
      ligands with a repertoire of kinetic binding profiles for CB2R.

PMID- 28747490
TI  - Allosteric auto-inhibition and activation of the Nedd4 family E3 ligase Itch.
AB  - The Nedd4 family E3 ligases are key regulators of cell growth and proliferation
      and are often misregulated in human cancers and other diseases. The ligase
      activities of Nedd4 E3s are tightly controlled via auto-inhibition. However, the
      molecular mechanism underlying Nedd4 E3 auto-inhibition and activation is poorly
      understood. Here, we show that the WW domains proceeding the catalytic HECT
      domain play an inhibitory role by binding directly to HECT in the Nedd4 E3 family
      member Itch. Our structural and biochemical analyses of Itch reveal that the WW2
      domain and a following linker allosterically lock HECT in an inactive state
      inhibiting E2-E3 transthiolation. Binding of the Ndfip1 adaptor or JNK1-mediated
      phosphorylation relieves the auto-inhibition of Itch in a WW2-dependent manner.
      Aberrant activation of Itch leads to migration defects of cortical neurons during
      development. Our study provides a new mechanism governing the regulation of Itch.

PMID- 28747491
TI  - Animal regeneration: ancestral character or evolutionary novelty?
AB  - An old question about regeneration is whether it is an ancestral character which
      is a general property of living matter, or whether it represents a set of
      specific adaptations to the different circumstances faced by different types of
      animal. In this review, some recent results on regeneration are assessed to see
      if they can throw any new light on this question. Evidence in favour of an
      ancestral character comes from the role of Wnt and bone morphogenetic protein
      signalling in controlling the pattern of whole-body regeneration in acoels, which
      are a basal group of bilaterian animals. On the other hand, there is some
      evidence for adaptive acquisition or maintenance of the regeneration of
      appendages based on the occurrence of severe non-lethal predation, the existence
      of some novel genes in regenerating organisms, and differences at the molecular
      level between apparently similar forms of regeneration. It is tentatively
      concluded that whole-body regeneration is an ancestral character although has
      been lost from most animal lineages. Appendage regeneration is more likely to
      represent a derived character resulting from many specific adaptations.

PMID- 28747492
TI  - Responsiveness to cigarette prices by different racial/ethnic groups of US
      adults.
AB  - OBJECTIVE: To evaluate the impact of cigarette prices on adult smoking for four
      US racial/ethnic groups: whites, African-Americans, Asians and Hispanics.
      METHODS: We analysed pooled cross-sectional data from the 2006/2007 and 2010/2011
      Tobacco Use Supplement to the Current Population Survey (n=339 921 adults aged
      18+) and cigarette price data from the Tax Burden on Tobacco. Using a two-part
      econometric model of cigarette demand that controlled for sociodemographic
      characteristics, state-level antismoking sentiment, local-level smoke-free air
      laws and monthly indicator, we estimated for each racial/ethnic group the price
      elasticities of smoking participation, smoking intensity and total demand for
      cigarettes. RESULTS: Smoking prevalence for whites, African-Americans, Asians and
      Hispanics during the study period was 18.3%, 16.1%, 8.2% and 11.3%, respectively.
      The price elasticity of smoking participation was statistically significant for
      whites, African-Americans, Asians and Hispanics at -0.26, -0.10, -0.42 and -0.11,
      respectively. The price elasticity of smoking intensity was statistically
      significant among whites (-0.22) and African-Americans (-0.17). Overall, the
      total price elasticity of cigarette demand was statistically significant for all
      racial/ethnic groups: 0.48 for whites, -0.27 for African-Americans, -0.22 for
      Asians and -0.15 for Hispanics. CONCLUSIONS: Our results suggest that raising
      cigarette prices, such as via tobacco tax increases, would result in reduced
      cigarette consumption for all racial/ethnic groups. The magnitude of the effect
      and the impact on cessation and reduced smoking intensity differ across these
      groups.

PMID- 28747493
TI  - Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host
      Transcription.
AB  - Viral hemorrhagic septicemia virus (VHSV) is a pathogenic fish rhabdovirus found
      in discrete locales throughout the Northern Hemisphere. VHSV infection of fish
      cells leads to upregulation of the host's virus detection response, but the virus
      quickly suppresses interferon (IFN) production and antiviral gene expression. By
      systematically screening each of the six VHSV structural and nonstructural genes,
      we identified matrix protein (M) as the virus' most potent antihost protein. Only
      M of VHSV genotype IV sublineage b (VHSV-IVb) suppressed mitochondrial antiviral
      signaling protein (MAVS) and type I IFN-induced gene expression in a dose
      dependent manner. M also suppressed the constitutively active simian virus 40
      (SV40) promoter and globally decreased cellular RNA levels. Chromatin
      immunoprecipitation (ChIP) studies illustrated that M inhibited RNA polymerase II
      (RNAP II) recruitment to gene promoters and decreased RNAP II C-terminal domain
      (CTD) Ser2 phosphorylation during VHSV infection. However, transcription directed
      by RNAP I to III was suppressed by M. To identify regions of functional
      importance, M proteins from a variety of VHSV strains were tested in cell-based
      transcriptional inhibition assays. M of a particular VHSV-Ia strain, F1, was
      significantly less potent than IVb M at inhibiting SV40/luciferase (Luc)
      expression yet differed by just 4 amino acids. Mutation of D62 to alanine alone,
      or in combination with an E181-to-alanine mutation (D62A E181A), dramatically
      reduced the ability of IVb M to suppress host transcription. Introducing either M
      D62A or D62A E181A mutations into VHSV-IVb via reverse genetics resulted in
      viruses that replicated efficiently but exhibited less cytotoxicity and reduced
      antitranscriptional activities, implicating M as a primary regulator of
      cytopathicity and host transcriptional suppression.IMPORTANCE Viruses must
      suppress host antiviral responses to replicate and spread between hosts. In these
      studies, we identified the matrix protein of the deadly fish novirhabdovirus VHSV
      as a critical mediator of host suppression during infection. Our studies
      indicated that M alone could block cellular gene expression at very low
      expression levels. We identified several subtle mutations in M that were less
      potent at suppressing host transcription. When these mutations were engineered
      back into recombinant viruses, the resulting viruses replicated well but elicited
      less toxicity in infected cells and activated host innate immune responses more
      robustly. These data demonstrated that VHSV M plays an important role in
      mediating both virus-induced cell toxicity and viral replication. Our data
      suggest that its roles in these two processes can be separated to design
      effective attenuated viruses for vaccine candidates.

PMID- 28747494
TI  - Bam35 tectivirus intraviral interaction map unveils new function and localization
      of phage ORFan proteins.
AB  - Tectiviridae comprises a group of tail-less, icosahedral, membrane-containing
      bacteriophages that can be divided into two groups by their hosts, either Gram
      negative or Gram-positive bacteria. While the first group is composed of PRD1 and
      nearly identical well characterized lytic viruses, the second one includes more
      variable temperate phages, like GIL16 or Bam35, whose hosts are Bacillus cereus
      and related Gram-positive bacteria.In the genome of Bam35, nearly half of the 32
      annotated open reading frames (ORFs) have no homologs in databases (ORFans),
      being putative proteins of unknown function, which hinders the understanding of
      their biology. With the aim of increasing the knowledge of the viral proteome, we
      carried out a comprehensive yeast two-hybrid analysis among all the putative
      proteins encoded by the Bam35 genome. The resulting protein interactome comprises
      76 unique interactions among 24 proteins, of which 12 have an unknown function.
      These results suggested that the P17 protein is the minor capsid protein of Bam35
      and P24 is the penton protein, being the latter also supported by iterative
      threading protein modeling. Moreover, the inner membrane transglycosylase protein
      P26 could have an additional structural role. We also detected interactions
      involving non-structural proteins, such as the DNA binding protein P1 and the
      genome terminal protein (P4), which was confirmed by co-immunoprecipitation of
      recombinant proteins. Altogether, our results provide a functional view of the
      Bam35 viral proteome, with a focus on the composition and organization of the
      viral particle.IMPORTANCE Tail-less viruses of the family Tectiviridae can infect
      commensal and pathogenic Gram-positive and Gram-negative bacteria. Moreover, they
      have been proposed to be at the evolutionary origin of several groups of large
      eukaryotic DNA viruses and self-replicating plasmids. However, due to their
      ancient origin and complex diversity, many tectiviral proteins are ORFans of
      unknown function.Comprehensive protein-protein interaction (PPI) analysis among
      viral proteins can eventually disclose biological mechanisms and thus provide new
      insights into protein function unattainable by studying proteins one by one. Here
      we comprehensively describe intraviral PPIs among tectivirus Bam35 proteins using
      multi-vector yeast two-hybrid screening that was further supported by co
      immunoprecipitation assays and protein structural models. This approach allowed
      us to propose new functions for known proteins and hypothesize on the biological
      role localization within the viral particle of some viral ORFan proteins that
      will be helpful for understanding the biology of Gram-positive tectivirus.

PMID- 28747495
TI  - Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High
      Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation.
AB  - A highly conserved threonine near the C terminus of gp120 of human
      immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) was
      investigated for its contributions to envelope protein function and virion
      infectivity. When this highly conserved Thr residue was substituted with anything
      other than serine (the other amino acid that can accept O-glycosylation), the
      resulting virus was noninfectious. We found that this Thr was critical for the
      association of gp120 with the virion and that amino acid substitution increased
      the amount of dissociated gp120 in the cell culture supernatant. When HIV virions
      were generated in cells overexpressing polypeptide N
      acetylgalactosaminyltransferase 1 (GalNAcT1), viral infectivity was increased 2.5
      fold compared to that of virus produced in wild-type HEK293T cells; infectivity
      was increased 8-fold when the Thr499Ser mutant was used. These infectivity
      enhancements were not observed when GalNAcT3 was used. Using HEK293T knockout
      cell lines totally devoid of the ability to perform O-linked glycosylation, we
      demonstrated production of normal levels of virions and normal levels of
      infectivity in the complete absence of O-linked carbohydrate. Our data indicate
      that O-glycosylation is not necessary for the natural replication cycle of HIV
      and SIV. Nonetheless, it remains theoretically possible that the repertoire of
      GalNAc transferase isoforms in natural target cells for HIV and SIV in vivo could
      result in O-glycosylation of the threonine residue in question and that this
      could boost the infectivity of virions beyond the levels seen in the absence of
      such O-glycosylation.IMPORTANCE Approximately 50% of the mass of the gp120
      envelope glycoprotein of both HIV and SIV is N-linked carbohydrate. One of the
      contributions of this N-linked carbohydrate is to shield conserved peptide
      sequences from recognition by humoral immunity. This N-linked glycosylation is
      one of the reasons that primary isolates of HIV and SIV are so heavily resistant
      to antibody-mediated neutralization. Much less studied is any potential
      contribution from O-linked glycosylation. The literature on this topic to date is
      somewhat confusing and ambiguous. Our studies described in this report
      demonstrate unambiguously that O-linked glycosylation is not necessary for the
      natural replication cycle of HIV and SIV. However, the door is not totally closed
      because of the diversity of numerous GalNAc transferase enzymes that initiate O
      linked carbohydrate attachment and the theoretical possibility that natural
      target cells for HIV and SIV in vivo could potentially complete such O-linked
      carbohydrate attachment to further increase infectivity.

PMID- 28747496
TI  - Parainfluenza Virus 5 Expressing Wild-Type or Prefusion Respiratory Syncytial
      Virus (RSV) Fusion Protein Protects Mice and Cotton Rats from RSV Challenge.
AB  - Human respiratory syncytial virus (RSV) is the leading cause of pediatric
      bronchiolitis and hospitalizations. RSV can also cause severe complications in
      elderly and immunocompromised individuals. There is no licensed vaccine. We
      previously generated a parainfluenza virus 5 (PIV5)-vectored vaccine candidate
      expressing the RSV fusion protein (F) that was immunogenic and protective in
      mice. In this work, our goal was to improve the original vaccine candidate by
      modifying the PIV5 vector or by modifying the RSV F antigen. We previously
      demonstrated that insertion of a foreign gene at the PIV5 small hydrophobic (SH)
      hemagglutinin-neuraminidase (HN) junction or deletion of PIV5 SH increased
      vaccine efficacy. Additionally, other groups have demonstrated that antibodies
      against the prefusion conformation of RSV F have more potent neutralizing
      activity than antibodies against the postfusion conformation. Therefore, to
      improve on our previously developed vaccine candidate, we inserted RSV F at the
      PIV5 SH-HN gene junction or used RSV F to replace PIV5 SH. We also engineered
      PIV5 to express a prefusion-stabilized F mutant. The candidates were tested in
      BALB/c mice via the intranasal route and induced both humoral and cell-mediated
      immunity. They also protected against RSV infection in the mouse lung. When they
      were administered intranasally or subcutaneously in cotton rats, the candidates
      were highly immunogenic and reduced RSV loads in both the upper and lower
      respiratory tracts. PIV5-RSV F was equally protective when administered
      intranasally or subcutaneously. In all cases, the prefusion F mutant did not
      induce higher neutralizing antibody titers than wild-type F. These results show
      that antibodies against both pre- and postfusion F are important for neutralizing
      RSV and should be considered when designing a vectored RSV vaccine. The findings
      also that indicate PIV5-RSV F may be administered subcutaneously, which is the
      preferred route for vaccinating infants, who may develop nasal congestion as a
      result of intranasal vaccination.IMPORTANCE Despite decades of research, human
      respiratory syncytial virus (RSV) is still a major health concern for which there
      is no vaccine. A parainfluenza virus 5-vectored vaccine expressing the native RSV
      fusion protein (F) has previously been shown to confer robust immunity against
      RSV infection in mice, cotton rats, and nonhuman primates. To improve our
      previous vaccine candidate, we developed four new candidates that incorporate
      modifications to the PIV5 backbone, replace native RSV F with a prefusion
      stabilized RSV F mutant, or combine both RSV F and PIV5 backbone modifications.
      In this work, we characterized the new vaccine candidates and tested their
      efficacies in both murine and cotton rat models of RSV infection. Most
      importantly, we found that PIV5-based RSV vaccine candidates were efficacious in
      preventing lower respiratory tract infection as well as in reducing the nasal
      viral load when administered via the subcutaneous route.

PMID- 28747497
TI  - Genetic Stability of Parainfluenza Virus 5-Vectored Human Respiratory Syncytial
      Virus Vaccine Candidates after In Vitro and In Vivo Passage.
AB  - Human respiratory syncytial virus (RSV) is the leading etiologic agent of lower
      respiratory tract infections in children, but no licensed vaccine exists.
      Previously, we developed two parainfluenza virus 5 (PIV5)-based RSV vaccine
      candidates that protect mice against RSV challenge. PIV5 was engineered to
      express either the RSV fusion protein (F) or the RSV major attachment
      glycoprotein (G) between the hemagglutinin-neuraminidase (HN) and RNA-dependent
      RNA polymerase (L) genes of the PIV5 genome [PIV5-RSV-F (HN-L) and PIV5-RSV-G (HN
      L), respectively]. To investigate the stability of the vaccine candidates in
      vitro, they were passaged in Vero cells at high and low multiplicities of
      infection (MOIs) for 11 generations and the genome sequences, growth kinetics,
      and protein expression of the resulting viruses were compared with those of the
      parent viruses. Sporadic mutations were detected in the consensus sequences of
      the viruses after high-MOI passages, and mutation rates increased under low-MOI
      passage conditions. None of the mutations abolished antigen expression. Increased
      numbers of mutations correlated with increased growth rates in vitro, indicating
      that the viruses evolved through the course of serial passages. We also examined
      the in vivo stability of the vaccine candidates after a single passage in African
      green monkeys. No mutations were detected in the consensus sequences of viruses
      collected from the bronchoalveolar lavage (BAL) fluid of the animals. In vivo,
      mutations in RSV G and PIV5 L were found in individual isolates of PIV5-RSV-G (HN
      L), but plaque isolates of PIV5-RSV-F (HN-L) had no mutations. To improve upon
      the PIV5-RSV-F (HN-L) candidate, additional vaccine candidates were generated in
      which the gene for RSV F was inserted into earlier positions in the PIV5 genome.
      These insertions did not negatively impact the sequence stability of the vaccine
      candidates. The results suggest that the RSV F and G gene insertions are stable
      in the PIV5 genome. However, the function of the foreign gene insertion may need
      to be considered when designing PIV5-based vaccines.IMPORTANCE The genetic
      stability of live viral vaccines is important for safety and efficacy. PIV5 is a
      promising live viral vector and has been used to develop vaccines. In this work,
      we examined the genetic stability of a PIV5-based RSV vaccine in vitro and in
      vivo We found that insertions of foreign genes, such as the RSV F and G genes,
      were stably maintained in the PIV5 genome and there was no mutation that
      abolished the expression of RSV F or G. Interestingly, the function of the
      inserted gene may have an impact on PIV5 genome stability.

PMID- 28747498
TI  - Pseudorabies virus US3-induced tunneling nanotubes contain stabilized
      microtubules, interact with neighbouring cells via cadherins and allow
      intercellular molecular communication.
AB  - Tunneling nanotubes (TNTs) are long bridge-like structures that connect
      eukaryotic cells and mediate intercellular communication. We found earlier that
      the conserved alphaherpesvirus US3 protein kinase induces long cell projections
      that contact distant cells and promote intercellular virus spread. In this
      report, we show that the US3-induced cell projections constitute TNTs. In
      addition, we report that US3-induced TNTs mediate intercellular transport of
      information (i.e. GFP) in the absence of other viral proteins. US3-induced TNTs
      are remarkably stable compared to most TNTs described in literature. In line with
      this, US3-induced TNTs were found to contain stabilized (acetylated and
      detyrosinated) microtubules. Transmission electron microscopy showed that virus
      particles are individually transported in membrane-bound vesicles in US3-induced
      TNTs and are released along the TNT and at the contact area between TNT and
      adjacent cell. Contact between US3-induced TNTs and acceptor cells is very
      stable, which correlated with a marked enrichment in adherens junction components
      beta-catenin and E-cadherin at the contact area. These data provide new
      structural insights in US3-induced TNTs and how they may contribute to
      intercellular communication and alphaherpesvirus spread.IMPORTANCE Tunneling
      nanotubes (TNT) represent an important, yet still poorly understood mode of long
      distance intercellular communication. We and others reported earlier that the
      conserved alphaherpesvirus US3 protein kinase induces long cellular protrusions
      in infected and transfected cells. Here, we show that US3-induced cell
      projections constitute TNTs, based on structural properties and transport of
      biomolecules. In addition, we report on different particular characteristics of
      US3-induced TNTs that aid to explain their remarkable stability compared to
      physiological TNTs. In addition, transmission electron microscopy assays indicate
      that, in infected cells, virions travel in the US3-induced TNTs in membranous
      transport vesicles, and leave the TNT via exocytosis. These data generate new
      fundamental insights in the biology of (US3-induced) TNTs, and how they may
      contribute to intercellular virus spread and communication.

PMID- 28747499
TI  - Effects of Inner Nuclear Membrane Proteins SUN1/UNC-84A and SUN2/UNC-84B on the
      Early Steps of HIV-1 Infection.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of dividing and nondividing
      cells involves regulatory interactions with the nuclear pore complex (NPC),
      followed by translocation to the nucleus and preferential integration into
      genomic areas in proximity to the inner nuclear membrane (INM). To identify host
      proteins that may contribute to these processes, we performed an overexpression
      screen of known membrane-associated NE proteins. We found that the integral
      transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest
      inhibitors of HIV-1 infection, respectively, and that suppression corresponds to
      defects in the accumulation of viral cDNA in the nucleus. While laboratory
      strains (HIV-1NL4.3 and HIV-1IIIB) are sensitive to SUN1-mediated inhibition, the
      transmitted founder viruses RHPA and ZM247 are largely resistant. Using chimeric
      viruses, we identified the HIV-1 capsid (CA) protein as a major determinant of
      sensitivity to SUN1, and in vitro-assembled capsid-nucleocapsid (CANC) nanotubes
      captured SUN1 and SUN2 from cell lysates. Finally, we generated SUN1-/- and SUN2
      /- cells by using CRISPR/Cas9 and found that the loss of SUN1 had no effect on
      HIV-1 infectivity, whereas the loss of SUN2 had a modest suppressive effect.
      Taken together, these observations suggest that SUN1 and SUN2 may function
      redundantly to modulate postentry, nuclear-associated steps of HIV-1
      infection.IMPORTANCE HIV-1 causes more than 1 million deaths per year. The life
      cycle of HIV-1 has been studied extensively, yet important steps that occur
      between viral capsid release into the cytoplasm and the expression of viral genes
      remain elusive. We propose here that the INM components SUN1 and SUN2, two
      members of the linker of nucleoskeleton and cytoskeleton (LINC) complex, may
      interact with incoming HIV-1 replication complexes and affect key steps of
      infection. While overexpression of these proteins reduces HIV-1 infection,
      disruption of the individual SUN2 and SUN1 genes leads to a mild reduction or no
      effect on infectivity, respectively. We speculate that SUN1/SUN2 may function
      redundantly in early HIV-1 infection steps and therefore influence HIV-1
      replication and pathogenesis.

PMID- 28747500
TI  - Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization
      Assessments.
AB  - In the search for effective immunologic interventions to prevent and treat HIV-1
      infection, standardized reference reagents are a cost-effective way to maintain
      robustness and reproducibility among immunological assays. To support planned and
      ongoing studies where clade C predominates, here we describe three virus panels,
      chosen from 200 well-characterized clade C envelope (Env)-pseudotyped viruses
      from early infection. All 200 Envs were expressed as a single round of
      replication pseudoviruses and were tested to quantify neutralization titers by 16
      broadly neutralizing antibodies (bnAbs) and sera from 30 subjects with chronic
      clade C infections. We selected large panels of 50 and 100 Envs either to
      characterize cross-reactive breadth for sera identified as having potent
      neutralization activity based on initial screening or to evaluate neutralization
      magnitude-breadth distributions of newly isolated antibodies. We identified these
      panels by downselection after hierarchical clustering of bnAb neutralization
      titers. The resulting panels represent the diversity of neutralization profiles
      throughout the range of virus sensitivities identified in the original panel of
      200 viruses. A small 12-Env panel was chosen to screen sera from vaccine trials
      or natural-infection studies for neutralization responses. We considered panels
      selected by previously described methods but favored a computationally informed
      method that enabled selection of viruses representing diverse neutralization
      sensitivity patterns, given that we do not a priori know what the neutralization
      response profile of vaccine sera will be relative to that of sera from infected
      individuals. The resulting 12-Env panel complements existing panels. Use of
      standardized panels enables direct comparisons of data from different trials and
      study sites testing HIV-1 clade C-specific products.IMPORTANCE HIV-1 group M
      includes nine clades and many recombinants. Clade C is the most common lineage,
      responsible for roughly half of current HIV-1 infections, and is a focus for
      vaccine design and testing. Standard reference reagents, particularly virus
      panels to study neutralization by antibodies, are crucial for developing cost
      effective and yet rigorous and reproducible assays against diverse examples of
      this variable virus. We developed clade C-specific panels for use as standardized
      reagents to monitor complex polyclonal sera for neutralization activity and to
      characterize the potency and breadth of cross-reactive neutralization by
      monoclonal antibodies, whether engineered or isolated from infected individuals.
      We chose from 200 southern African, clade C envelope-pseudotyped viruses with
      neutralization titers against 16 broadly neutralizing antibodies and 30 sera from
      chronic clade C infections. We selected panels to represent the diversity of bnAb
      neutralization profiles and Env neutralization sensitivities. Use of standard
      virus panels can facilitate comparison of results across studies and sites.

PMID- 28747501
TI  - Murine Gammaherpesvirus 68 Expressing Kaposi Sarcoma-Associated Herpesvirus
      Latency-Associated Nuclear Antigen (LANA) Reveals both Functional Conservation
      and Divergence in LANA Homologs.
AB  - Latency-associated nuclear antigen (LANA) is a multifunctional protein encoded by
      members of the Rhadinovirus genus of gammaherpesviruses. Studies using murine
      gammaherpesvirus 68 (MHV68) demonstrated that LANA is important for acute
      replication, latency establishment, and reactivation in vivo Despite structural
      similarities in their DNA-binding domains (DBDs), LANA homologs from Kaposi
      sarcoma-associated herpesvirus (KSHV) and MHV68 exhibit considerable sequence
      divergence. We sought to determine if KSHV and MHV68 LANA homologs are
      functionally interchangeable. We generated an MHV68 virus that encodes KSHV LANA
      (kLANA) in place of MHV68 LANA (mLANA) and evaluated the virus's capacity to
      replicate, establish and maintain latency, and reactivate. kLANA knock-in (KLKI)
      MHV68 was replication competent in vitro and in vivo but exhibited slower growth
      kinetics and lower titers than wild-type (WT) MHV68. Following inoculation of
      mice, KLKI MHV68 established and maintained latency in splenocytes and peritoneal
      cells but did not reactivate efficiently ex vivo kLANA repressed the MHV68
      promoter for ORF50, the gene that encodes the major lytic transactivator protein
      RTA, while mLANA did not, suggesting a likely mechanism for the KLKI MHV68
      phenotypes. Bypassing this repression by providing MHV68 RTA in trans rescued
      KLKI MHV68 replication in tissue culture and enabled detection of KLKI MHV68
      reactivation ex vivo These data demonstrate that kLANA and mLANA are functionally
      interchangeable for establishment and maintenance of latency and suggest that
      repression of lytic replication by kLANA, as previously shown with KSHV, is a
      kLANA-specific function that is transferable to MHV68.IMPORTANCE Kaposi sarcoma
      associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68) are members
      of the Rhadinovirus genus of gammaherpesviruses. These viruses establish lifelong
      infections that place their respective human and murine hosts at risk for cancer.
      Latency-associated nuclear antigen (LANA) is a conserved Rhadinovirus protein
      that is necessary for long-term chronic infection by these viruses. To better
      understand the conserved functions performed by LANA homologs, we generated a
      recombinant MHV68 virus that encodes the KSHV LANA protein in place of the MHV68
      LANA homolog. We determined that the KSHV LANA protein is capable of supporting
      MHV68 latency in a mouse model of chronic infection but also functions to repress
      viral replication. This work describes an in vivo model system for defining
      evolutionarily conserved and divergent functions of LANA homologs in Rhadinovirus
      infection and disease.

PMID- 28747502
TI  - Permissivity of Dipeptidyl Peptidase 4 Orthologs to Middle East Respiratory
      Syndrome Coronavirus Is Governed by Glycosylation and Other Complex Determinants.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl
      peptidase 4 (DPP4) as an entry receptor. While bat, camel, and human DPP4 support
      MERS-CoV infection, several DPP4 orthologs, including mouse, ferret, hamster, and
      guinea pig DPP4, do not. Previous work revealed that glycosylation of mouse DPP4
      plays a role in blocking MERS-CoV infection. Here, we tested whether
      glycosylation also acts as a determinant of permissivity for ferret, hamster, and
      guinea pig DPP4. We found that, while glycosylation plays an important role in
      these orthologs, additional sequence and structural determinants impact their
      ability to act as functional receptors for MERS-CoV. These results provide
      insight into DPP4 species-specific differences impacting MERS-CoV host range and
      better inform our understanding of virus-receptor interactions associated with
      disease emergence and host susceptibility.IMPORTANCE MERS-CoV is a recently
      emerged zoonotic virus that is still circulating in the human population with an
      ~35% mortality rate. With no available vaccines or therapeutics, the study of
      MERS-CoV pathogenesis is crucial for its control and prevention. However, in vivo
      studies are limited because MERS-CoV cannot infect wild-type mice due to
      incompatibilities between the virus spike and the mouse host cell receptor, mouse
      DPP4 (mDPP4). Specifically, mDPP4 has a nonconserved glycosylation site that acts
      as a barrier to MERS-CoV infection. Thus, one mouse model strategy has been to
      modify the mouse genome to remove this glycosylation site. Here, we investigated
      whether glycosylation acts as a barrier to infection for other nonpermissive
      small-animal species, namely, ferret, guinea pig, and hamster. Understanding the
      virus-receptor interactions for these DPP4 orthologs will help in the development
      of additional animal models while also revealing species-specific differences
      impacting MERS-CoV host range.

PMID- 28747503
TI  - Identification of Vaccinia Virus Replisome and Transcriptome Proteins by
      Isolation of Proteins on Nascent DNA Coupled with Mass Spectrometry.
AB  - Poxviruses replicate within the cytoplasm and encode proteins for DNA and mRNA
      synthesis. To investigate poxvirus replication and transcription from a new
      perspective, we incorporated 5-ethynyl-2'-deoxyuridine (EdU) into nascent DNA in
      cells infected with vaccinia virus (VACV). The EdU-labeled DNA was conjugated to
      fluor- or biotin-azide and visualized by confocal, superresolution, and
      transmission electron microscopy. Nuclear labeling decreased dramatically after
      infection, accompanied by intense labeling of cytoplasmic foci. The nascent DNA
      colocalized with the VACV single-stranded DNA binding protein I3 in multiple
      puncta throughout the interior of factories, which were surrounded by endoplasmic
      reticulum. Complexes containing EdU-biotin-labeled DNA cross-linked to proteins
      were captured on streptavidin beads. After elution and proteolysis, the peptides
      were analyzed by mass spectrometry to identify proteins associated with nascent
      DNA. The known viral replication proteins, a telomere binding protein, and a
      protein kinase were associated with nascent DNA, as were the DNA-dependent RNA
      polymerase and intermediate- and late-stage transcription initiation and
      elongation factors, plus the capping and methylating enzymes. These results
      suggested that the replicating pool of DNA is transcribed and that few if any
      additional viral proteins directly engaged in replication and transcription
      remain to be discovered. Among the host proteins identified by mass spectrometry,
      topoisomerases IIalpha and IIbeta and PCNA were noteworthy. The association of
      the topoisomerases with nascent DNA was dependent on expression of the viral DNA
      ligase, in accord with previous proteomic studies. Further investigations are
      needed to determine possible roles for PCNA and other host proteins
      detected.IMPORTANCE Poxviruses, unlike many well-characterized animal DNA
      viruses, replicate entirely within the cytoplasm of animal cells, raising
      questions regarding the relative roles of viral and host proteins. We adapted
      newly developed procedures for click chemistry and iPOND (Isolation of proteins
      on nascent DNA) to investigate vaccinia virus (VACV), the prototype poxvirus.
      Nuclear DNA synthesis ceased almost immediately following VACV infection,
      followed swiftly by the synthesis of viral DNA within discrete cytoplasmic foci.
      All viral proteins known from genetic and proteomic studies to be required for
      poxvirus DNA replication were identified in the complexes containing nascent DNA.
      The additional detection of the viral DNA-dependent RNA polymerase and
      intermediate and late transcription factors provided evidence for a temporal
      coupling of replication and transcription. Further studies are needed to assess
      the potential roles of host proteins, including topoisomerases IIalpha and IIbeta
      and PCNA, which were found associated with nascent DNA.

PMID- 28747504
TI  - Targeted Genome Sequencing Reveals Varicella-Zoster Virus Open Reading Frame 12
      Deletion.
AB  - The neurotropic herpesvirus varicella-zoster virus (VZV) establishes a lifelong
      latent infection in humans following primary infection. The low abundance of VZV
      nucleic acids in human neurons has hindered an understanding of the mechanisms
      that regulate viral gene transcription during latency. To overcome this critical
      barrier, we optimized a targeted capture protocol to enrich VZV DNA and cDNA
      prior to whole-genome/transcriptome sequence analysis. Since the VZV genome is
      remarkably stable, it was surprising to detect that VZV32, a VZV laboratory
      strain with no discernible growth defect in tissue culture, contained a 2,158-bp
      deletion in open reading frame (ORF) 12. Consequently, ORF 12 and 13 protein
      expression was abolished and Akt phosphorylation was inhibited. The discovery of
      the ORF 12 deletion, revealed through targeted genome sequencing analysis, points
      to the need to authenticate the VZV genome when the virus is propagated in tissue
      culture.IMPORTANCE Viruses isolated from clinical samples often undergo genetic
      modifications when cultured in the laboratory. Historically, VZV is among the
      most genetically stable herpesviruses, a notion supported by more than 60
      complete genome sequences from multiple isolates and following multiple in vitro
      passages. However, application of enrichment protocols to targeted genome
      sequencing revealed the unexpected deletion of a significant portion of VZV ORF
      12 following propagation in cultured human fibroblast cells. While the enrichment
      protocol did not introduce bias in either the virus genome or transcriptome, the
      findings indicate the need for authentication of VZV by sequencing when the virus
      is propagated in tissue culture.

PMID- 28747505
TI  - Insufficient Innate Immunity Contributes to the Susceptibility of the Castaneous
      Mouse to Orthopoxvirus Infection.
AB  - The castaneous (CAST) mouse, a wild-derived inbred strain, is highly susceptible
      to orthopoxvirus infection by intranasal and systemic routes. The 50% lethal
      intraperitoneal dose of vaccinia virus (VACV) was 3 PFU for CAST mice, whereas
      BALB/c mice survived 106 PFU. At all times and in all organs analyzed, virus
      titers were higher in CAST than in BALB/c mice. In individual CAST mice,
      luciferase-expressing VACV was seen to replicate rapidly leading to death,
      whereas virus levels increased for a few days and then declined in BALB/c mice.
      Increases in gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF
      alpha) were delayed and low in CAST mice compared to BALB/c mice following VACV
      infection or poly(I-C) inoculation, consistent with differences in innate immune
      responses. In addition, naive CAST mice had considerably lower numbers of NK and
      T cells than BALB/c mice. The percentage of IFN-gamma-producing CD4+ and CD8+ T
      cells increased following infection of CAST mice only after considerable virus
      spread, and the absolute cell numbers remained low. Administration of exogenous
      IFN-gamma or -alpha to CAST mice before or during the first days of infection
      suppressed virus replication and prolonged survival, allowing the mice to make
      adaptive CD4+ and CD8+ T cell responses that were necessary to clear the virus
      after cessation of interferon treatment. Thus, insufficient innate cytokine and
      cellular immune responses contribute to the unique susceptibility of CAST mice to
      VACV, whereas the adaptive immune response can be protective only if virus
      replication is suppressed during the first several days of infection.IMPORTANCE
      Most inbred mouse strains are relatively resistant to orthopoxviruses. The
      castaneous (CAST) mouse is a notable exception, exhibiting extreme vulnerability
      to monkeypox virus, cowpox virus, and vaccinia virus and thus providing a unique
      model for studying pathogenicity, immunity, vaccines, and antiviral drugs. To
      fully utilize the CAST mouse for such purposes, it is necessary to understand the
      basis for virus susceptibility. We showed that naive CAST mice make low IFN-gamma
      and TNF-alpha responses and have low levels of NK cells and CD4+ and CD8+ T cells
      compared to a resistant classical inbred mouse strain. Attenuating virus
      replication with one or more doses of exogenous IFN-alpha or -gamma before or
      during the first few days of infection enabled the development of adaptive
      cellular immunity and clearance of virus. Further genetic studies may reveal the
      basis for the low innate immunity.

PMID- 28747506
TI  - Hepatitis C Virus Induces the Localization of Lipid Rafts to Autophagosomes for
      Its RNA Replication.
AB  - Autophagy plays important roles in maintaining cellular homeostasis. It uses
      double- or multiple-membrane vesicles termed autophagosomes to remove protein
      aggregates and damaged organelles from the cytoplasm for recycling. Hepatitis C
      virus (HCV) has been shown to induce autophagy to enhance its own replication.
      Here we describe a procedure that combines membrane flotation and affinity
      chromatography for the purification of autophagosomes from cells that harbor an
      HCV subgenomic RNA replicon. The purified autophagosomes had double- or multiple
      membrane structures with a diameter ranging from 200 nm to 600 nm. The analysis
      of proteins associated with HCV-induced autophagosomes by proteomics led to the
      identification of HCV nonstructural proteins as well as proteins involved in
      membrane trafficking. Notably, caveolin-1, caveolin-2, and annexin A2, which are
      proteins associated with lipid rafts, were also identified. The association of
      lipid rafts with HCV-induced autophagosomes was confirmed by Western blotting,
      immunofluorescence microscopy, and immunoelectron microscopy. Their association
      with autophagosomes was also confirmed in HCV-infected cells. The association of
      lipid rafts with autophagosomes was specific to HCV, as it was not detected in
      autophagosomes induced by nutrient starvation. Further analysis indicated that
      the autophagosomes purified from HCV replicon cells could mediate HCV RNA
      replication in a lipid raft-dependent manner, as the depletion of cholesterol, a
      major component of lipid rafts, from autophagosomes abolished HCV RNA
      replication. Our studies thus demonstrated that HCV could specifically induce the
      association of lipid rafts with autophagosomes for its RNA replication.IMPORTANCE
      HCV can cause severe liver diseases, including cirrhosis and hepatocellular
      carcinoma, and is one of the most important human pathogens. Infection with HCV
      can lead to the reorganization of membrane structures in its host cells,
      including the induction of autophagosomes. In this study, we developed a
      procedure to purify HCV-induced autophagosomes and demonstrated that HCV could
      induce the localization of lipid rafts to autophagosomes to mediate its RNA
      replication. This finding provided important information for further
      understanding the life cycle of HCV and its interaction with the host cells.

PMID- 28747507
TI  - Roles of Cellular NSF Protein in Entry and Nuclear Egress of Budded Virions of
      Autographa californica Multiple Nucleopolyhedrovirus.
AB  - In eukaryotic cells, the soluble N-ethylmaleimide-sensitive factor (NSF)
      attachment protein receptor (SNARE) proteins comprise the minimal machinery that
      triggers fusion of transport vesicles with their target membranes. Comparative
      studies revealed that genes encoding the components of the SNARE system are
      highly conserved in yeast, insect, and human genomes. Upon infection of insect
      cells by the virus Autographa californica multiple nucleopolyhedrovirus (AcMNPV),
      the transcript levels of most SNARE genes initially were upregulated. We found
      that overexpression of dominant-negative (DN) forms of NSF or knockdown of the
      expression of NSF, the key regulator of the SNARE system, significantly affected
      infectious AcMNPV production. In cells expressing DN NSF, entering virions were
      trapped in the cytoplasm or transported to the nucleus with low efficiency. The
      presence of DN NSF also moderately reduced trafficking of the viral envelope
      glycoprotein GP64 to the plasma membrane but dramatically inhibited production of
      infectious budded virions (BV). Transmission electron microscopy analysis of
      infections in cells expressing DN NSF revealed that progeny nucleocapsids were
      retained in a perinuclear space surrounded by inner and outer nuclear membranes.
      Several baculovirus conserved (core) proteins (Ac76, Ac78, GP41, Ac93, and Ac103)
      that are important for infectious budded virion production were found to
      associate with NSF, and NSF was detected within the assembled BV. Together, these
      data indicate that the cellular SNARE system is involved in AcMNPV infection and
      that NSF is required for efficient entry and nuclear egress of budded virions of
      AcMNPV.IMPORTANCE Little is known regarding the complex interplay between
      cellular factors and baculoviruses during viral entry and egress. Here, we
      examined the cellular SNARE system, which mediates the fusion of vesicles in
      healthy cells, and its relation to baculovirus infection. Using a DN approach and
      RNA interference knockdown, we demonstrated that a general disruption of the
      SNARE machinery significantly inhibited the production of infectious BV of
      AcMNPV. The presence of a DN NSF protein resulted in low-efficiency entry of BV
      and the retention of progeny nucleocapsids in the perinuclear space during
      egress. Combined with these effects, we also found that several conserved (core)
      baculovirus proteins closely associate with NSF, and these results suggest their
      involvement in the egress of BV. Our findings are the first to demonstrate that
      the SNARE system is required for efficient entry of BV and nuclear egress of
      progeny nucleocapsids of baculoviruses.

PMID- 28747508
TI  - MUTATIONS IN THE E2 GLYCOPROTEIN AND THE 3' UNTRANSLATED REGION ENHANCE
      CHIKUNGUNYA VIRUS VIRULENCE IN MICE.
AB  - Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes
      debilitating musculoskeletal pain and inflammation and can persist for months to
      years after acute infection. Although studies in humans and experimentally
      infected animals suggest that CHIKV infection persists in musculoskeletal
      tissues, the mechanisms for this remain poorly understood. To evaluate this
      further, we isolated CHIKV from the serum of persistently infected Rag1-/- mice
      at day 28. When inoculated into naive WT mice, this persistently circulating
      CHIKV strain displayed a capacity for earlier dissemination and greater
      pathogenicity compared with the parental virus. Sequence analysis revealed a
      nonsynonymous mutation in the E2 glycoprotein (E2 K200R) and a deletion within
      the 3' untranslated region (3' -UTR). Introduction of these changes into the
      parental virus conferred enhanced virulence in mice although a primary tropism
      for musculoskeletal tissues was maintained. The E2 K200R mutation was largely
      responsible for enhanced viral dissemination and pathogenicity, although these
      effects were augmented by the 3' -UTR deletion. Finally, studies in Irf3/Irf7-/-
      and Ifnar1-/- mice suggest that the E2 K200R mutation enhances viral
      dissemination from the site of inoculation independently of IRF3, IRF7, and
      IFNAR1 mediated responses. As our findings reveal viral determinants of CHIKV
      dissemination and pathogenicity, their further study should help to elucidate
      host-virus interactions that determine acute and chronic CHIKV
      infection.IMPORTANCE CHIKV is a globally-spreading, mosquito-transmitted virus
      that causes debilitating acute and chronic musculoskeletal disease in humans. The
      viral genetic determinants that dictate acute and chronic disease severity are
      not understood. To improve our understanding of CHIKV pathogenesis, we evaluated
      a CHIKV strain isolated from the serum of chronically-infected immunocompromised
      mice. Sequence analysis of this persistent CHIKV strain identified two mutations,
      an amino acid change in the E2 viral attachment protein and a deletion within the
      3' -UTR of the viral genome. We identified roles for these mutations in
      enhancement of viral dissemination from the inoculation site and in disease
      severity. These data improve our understanding of the viral determinants of CHIKV
      pathogenesis and adaptive changes that occur during viral persistence.

PMID- 28747509
TI  - A Domain of Herpes Simplex Virus pUL33 Required To Release Monomeric Viral
      Genomes from Cleaved Concatemeric DNA.
AB  - Monomeric herpesvirus DNA is cleaved from concatemers and inserted into preformed
      capsids through the actions of the viral terminase. The terminase of herpes
      simplex virus (HSV) is composed of three subunits encoded by UL15, UL28, and
      UL33. The UL33-encoded protein (pUL33) interacts with pUL28, but its precise role
      in the DNA cleavage and packaging reaction is unclear. To investigate the
      function of pUL33, we generated a panel of recombinant viruses with either
      deletions or substitutions in the most conserved regions of UL33 using a
      bacterial artificial chromosome system. Deletion of 11 amino acids (residues 50
      to 60 or residues 110 to 120) precluded viral replication, whereas the truncation
      of the last 10 amino acids from the pUL33 C terminus did not affect viral
      replication or the interaction of pUL33 with pUL28. Mutations that replaced the
      lysine at codon 110 and the arginine at codon 111 with alanine codons failed to
      replicate, and the pUL33 mutant interacted with pUL28 less efficiently.
      Interestingly, genomic termini of the large (L) and small (S) components were
      detected readily in cells infected with these mutants, indicating that
      concatemeric DNA was cleaved efficiently. However, the release of monomeric
      genomes as assessed by pulsed-field gel electrophoresis was greatly diminished,
      and DNA-containing capsids were not observed. These results suggest that pUL33 is
      necessary for one of the two viral DNA cleavage events required to release
      individual genomes from concatemeric viral DNA.IMPORTANCE This paper shows a role
      for pUL33 in one of the two DNA cleavage events required to release monomeric
      genomes from concatemeric viral DNA. This is the first time that such a phenotype
      has been observed and is the first identification of a function of this protein
      relevant to DNA packaging other than its interaction with other terminase
      components.

PMID- 28747510
TI  - Nonspecific block of voltage-gated potassium channels has greater effect on
      distal schaffer collaterals than proximal schaffer collaterals during periods of
      high activity.
AB  - Previous studies established different responses between proximal and distal
      portions of Schaffer collateral axons during high-frequency and burst
      stimulation, with distal axons demonstrating biphasic changes in excitability
      (hyperexcitability followed by depression), but proximal axons showing only
      monophasic depression. Voltage-dependent potassium (KV) channels are important
      determinants of axonal excitability, and block of KV channels can promote axon
      hyperexcitability. We therefore hypothesized that block of KV channels should
      lead to biphasic response changes in proximal Schaffer collaterals, like those
      seen in distal Schaffer collaterals. To test this hypothesis, we made
      extracellular recordings of distal Schaffer collateral responses in stratum
      radiatum of hippocampal area CA1 and proximal Schaffer collateral responses in
      stratum pyramidale of area CA3 during high-frequency stimulation (HFS) at 100 Hz
      and burst stimulation at 200 msec intervals (5 Hz or theta frequency). We then
      applied a nonselective KV channel blocker, tetraethlylammonium (TEA, 10 mmol/L)
      or 4-aminopyridine (4-AP, 100 MUmol/L), and assessed effects on Schaffer
      collateral responses. Surprisingly, block of KV channels had little or no effect
      on proximal Schaffer collateral responses during high-frequency or burst
      stimulation. In contrast, KV channel blockade caused more rapid depression of
      distal Schaffer collateral responses during both high-frequency and burst
      stimulation. These findings indicate that KV channels are important for
      maintaining distal, but not proximal, Schaffer collateral excitability during
      period of sustained high activity. Differential sensitivity of distal versus
      proximal Schaffer collaterals to KV channel block may reflect differences in
      channel density, diversity, or subcellular localization.

PMID- 28747511
TI  - Autologous minced muscle grafts improve endogenous fracture healing and muscle
      strength after musculoskeletal trauma.
AB  - The deleterious impact of concomitant muscle injury on fracture healing and limb
      function is commonly considered part of the natural sequela of orthopedic trauma.
      Recent reports suggest that heightened inflammation in the surrounding
      traumatized musculature is a primary determinant of fracture healing. Relatedly,
      there are emerging potential therapeutic approaches for severe muscle trauma
      (e.g., volumetric muscle loss [VML] injury), such as autologous minced muscle
      grafts (1 mm3 pieces of muscle; GRAFT), that can partially prevent chronic
      functional deficits and appear to have an immunomodulatory effect within VML
      injured muscle. The primary goal of this study was to determine if repair of VML
      injury with GRAFT rescues impaired fracture healing and improves the strength of
      the traumatized muscle in a male Lewis rat model of tibia open fracture. The most
      salient findings of the study were: (1) tibialis anterior (TA) muscle repair with
      GRAFT improved endogenous healing of fractured tibia and improved the functional
      outcome of muscle regeneration; (2) GRAFT repair attenuated the
      monocyte/macrophage (CD45+CDllb+) and T lymphocyte (CD3+) response to VML injury;
      (3) TA muscle protein concentrations of MCP1, IL-10, and IGF-1 were augmented in
      a proregenerative manner by GRAFT repair; (4) VML injury concomitant with
      osteotomy induced a heightened systemic presence of alarmins (e.g., soluble RAGE)
      and leukocytes (e.g., monocytes), and depressed IGF-1 concentration, which GRAFT
      repair ameliorated. Collectively, these data indicate that repair of VML injury
      with a regenerative therapy can modulate the inflammatory and regenerative
      phenotype of the treated muscle and in association improve musculoskeletal
      healing.

PMID- 28747512
TI  - Charting the "unknown unknowns" of cancer progression.
AB  - Integrated computational and experimental strategies reveal previously unknown
      regulatory programs underlying metastatic disease.

PMID- 28747513
TI  - Repression of BET activity sensitizes homologous recombination-proficient cancers
      to PARP inhibition.
AB  - Strategies to enhance response to poly(adenosine diphosphate-ribose) polymerase
      inhibitor (PARPi) in primary and acquired homologous recombination (HR)
      proficient tumors would be a major advance in cancer care. We used a drug synergy
      screen that combined a PARPi, olaparib, with 20 well-characterized epigenetic
      drugs and identified bromodomain and extraterminal domain inhibitors (BETis; JQ1,
      I-BET762, and OTX015) as drugs that acted synergistically with olaparib in HR
      proficient cancer cells. Functional assays demonstrated that repressed BET
      activity reduces HR and thus enhances PARPi-induced DNA damage in cancer cells.
      We also found that inhibition or depletion of BET proteins impairs transcription
      of BRCA1 and RAD51, two genes essential for HR. Moreover, BETi treatment
      sensitized tumors to PARP inhibition in preclinical animal models of HR
      proficient breast and ovarian cancers. Finally, we showed that the BRD4 gene was
      focally amplified across 20 types of common cancers. Combination with BETi could
      greatly expand the utility of PARP inhibition to patients with HR-proficient
      cancer.

PMID- 28747515
TI  - Erratum for the Research Article: "Targeting KRAS-dependent tumors with AZD4785,
      a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS" by S. J.
      Ross, A. S. Revenko, L. L. Hanson, R. Ellston, A. Staniszewska, N. Whalley, S. K.
      Pandey, M. Revill, C. Rooney, L. K. Buckett, S. K. Klein, K. Hudson, B. P. Monia,
      M. Zinda, D. C. Blakey, P. D. Lyne, A. R. Macleod.

PMID- 28747514
TI  - Mechanoresponsive stem cells to target cancer metastases through biophysical
      cues.
AB  - Despite decades of effort, little progress has been made to improve the treatment
      of cancer metastases. To leverage the central role of the mechanoenvironment in
      cancer metastasis, we present a mechanoresponsive cell system (MRCS) to
      selectively identify and treat cancer metastases by targeting the specific
      biophysical cues in the tumor niche in vivo. Our MRCS uses mechanosensitive
      promoter-driven mesenchymal stem cell (MSC)-based vectors, which selectively home
      to and target cancer metastases in response to specific mechanical cues to
      deliver therapeutics to effectively kill cancer cells, as demonstrated in a
      metastatic breast cancer mouse model. Our data suggest a strong correlation
      between collagen cross-linking and increased tissue stiffness at the metastatic
      sites, where our MRCS is specifically activated by the specific cancer-associated
      mechano-cues. MRCS has markedly reduced deleterious effects compared to MSCs
      constitutively expressing therapeutics. MRCS indicates that biophysical cues,
      specifically matrix stiffness, are appealing targets for cancer treatment due to
      their long persistence in the body (measured in years), making them refractory to
      the development of resistance to treatment. Our MRCS can serve as a platform for
      future diagnostics and therapies targeting aberrant tissue stiffness in
      conditions such as cancer and fibrotic diseases, and it should help to elucidate
      mechanobiology and reveal what cells "feel" in the microenvironment in vivo.

PMID- 28747516
TI  - Redundant and diverse intranodal pacemakers and conduction pathways protect the
      human sinoatrial node from failure.
AB  - The human sinoatrial node (SAN) efficiently maintains heart rhythm even under
      adverse conditions. However, the specific mechanisms involved in the human SAN's
      ability to prevent rhythm failure, also referred to as its robustness, are
      unknown. Challenges exist because the three-dimensional (3D) intramural structure
      of the human SAN differs from well-studied animal models, and clinical electrode
      recordings are limited to only surface atrial activation. Hence, to innovate the
      translational study of human SAN structural and functional robustness, we
      integrated intramural optical mapping, 3D histology reconstruction, and molecular
      mapping of the ex vivo human heart. When challenged with adenosine or atrial
      pacing, redundant intranodal pacemakers within the human SAN maintained
      automaticity and delivered electrical impulses to the atria through sinoatrial
      conduction pathways (SACPs), thereby ensuring a fail-safe mechanism for robust
      maintenance of sinus rhythm. During adenosine perturbation, the primary central
      SAN pacemaker was suppressed, whereas previously inactive superior or inferior
      intranodal pacemakers took over automaticity maintenance. Sinus rhythm was also
      rescued by activation of another SACP when the preferential SACP was suppressed,
      suggesting two independent fail-safe mechanisms for automaticity and conduction.
      The fail-safe mechanism in response to adenosine challenge is orchestrated by
      heterogeneous differences in adenosine A1 receptors and downstream GIRK4 channel
      protein expressions across the SAN complex. Only failure of all pacemakers and/or
      SACPs resulted in SAN arrest or conduction block. Our results unmasked reserve
      mechanisms that protect the human SAN pacemaker and conduction complex from
      rhythm failure, which may contribute to treatment of SAN arrhythmias.

PMID- 28747517
TI  - A soft robotic exosuit improves walking in patients after stroke.
AB  - Stroke-induced hemiparetic gait is characteristically slow and metabolically
      expensive. Passive assistive devices such as ankle-foot orthoses are often
      prescribed to increase function and independence after stroke; however, walking
      remains highly impaired despite-and perhaps because of-their use. We sought to
      determine whether a soft wearable robot (exosuit) designed to supplement the
      paretic limb's residual ability to generate both forward propulsion and ground
      clearance could facilitate more normal walking after stroke. Exosuits transmit
      mechanical power generated by actuators to a wearer through the interaction of
      garment-like, functional textile anchors and cable-based transmissions. We
      evaluated the immediate effects of an exosuit actively assisting the paretic limb
      of individuals in the chronic phase of stroke recovery during treadmill and
      overground walking. Using controlled, treadmill-based biomechanical
      investigation, we demonstrate that exosuits can function in synchrony with a
      wearer's paretic limb to facilitate an immediate 5.33 +/- 0.91 degrees  increase
      in the paretic ankle's swing phase dorsiflexion and 11 +/- 3% increase in the
      paretic limb's generation of forward propulsion (P < 0.05). These improvements in
      paretic limb function contributed to a 20 +/- 4% reduction in forward propulsion
      interlimb asymmetry and a 10 +/- 3% reduction in the energy cost of walking,
      which is equivalent to a 32 +/- 9% reduction in the metabolic burden associated
      with poststroke walking. Relatively low assistance (~12% of biological torques)
      delivered with a lightweight and nonrestrictive exosuit was sufficient to
      facilitate more normal walking in ambulatory individuals after stroke. Future
      work will focus on understanding how exosuit-induced improvements in walking
      performance may be leveraged to improve mobility after stroke.

PMID- 28747518
TI  - Targeted Molecular Radiotherapy of Pediatric Solid Tumors Using a Radioiodinated
      Alkyl-Phospholipid Ether Analog.
AB  - External-beam radiotherapy plays a critical role in the treatment of most
      pediatric solid tumors. Particularly in children, achieving an optimal
      therapeutic index to avoid damage to normal tissue is extremely important.
      Consequently, in metastatic disease, the utility of external-beam radiotherapy is
      limited. Molecular radiotherapy with tumor-targeted radionuclides may overcome
      some of these challenges, but to date there exists no single cancer-selective
      agent capable of treating various pediatric malignancies independently of their
      histopathologic origin. We tested the therapeutic potential of the clinical-grade
      alkyl-phospholipid ether analog CLR1404, 18-(p-iodophenyl)octadecyl
      phosphocholine, as a scaffold for tumor-targeted radiotherapy of pediatric
      malignancies. Methods: Uptake of CLR1404 by pediatric solid tumor cells was
      tested in vitro by flow cytometry and in vivo by PET/CT imaging and dosimetry.
      The therapeutic potential of 131I-CLR1404 was evaluated in xenograft models.
      Results: In vitro, fluorescent CLR1404-BODIPY showed significant selective uptake
      in a variety of pediatric cancer lines compared with normal controls. In vivo
      tumor-targeted uptake in mouse xenograft models using 124I-CLR1404 was confirmed
      by imaging. Single-dose intravenous injection of 131I-CLR1404 significantly
      delayed tumor growth in all rodent pediatric xenograft models and extended animal
      survival while demonstrating a favorable side effect profile. Conclusion:131I
      CLR1404 has the potential to become a tumor-targeted radiotherapeutic drug with
      broad applicability in pediatric oncology. Because 131I-CLR1404 has entered
      clinical trials in adults, our data warrant the development of pediatric clinical
      trials for this particularly vulnerable patient population.

PMID- 28747519
TI  - The Impact of Adding Sentinel Node Biopsy to Extended Pelvic Lymph Node
      Dissection on Biochemical Recurrence in Prostate Cancer Patients Treated with
      Robot-Assisted Radical Prostatectomy.
AB  - The benefit of adding sentinel node biopsy (SNB) to extended pelvic lymph node
      dissection (ePLND) remains controversial. The aim of our study was to evaluate
      biochemical recurrence (BCR) after robot-assisted radical prostatectomy and ePLND
      in prostate cancer patients, stratified by the application of SNB. The results
      were compared with the predictions of the updated Memorial Sloan Kettering Cancer
      Center nomogram. Methods: Between January 2006 and November 2016, 920 patients
      underwent robot-assisted radical prostatectomy and ePLND with or without SNB (184
      and 736 patients, respectively). BCR was defined as 2 consecutive prostate
      specific antigen rises of at least 0.2 ng/mL. The Kaplan-Meier method and Cox
      regression analyses were used to identify predictors of BCR. Results: Median
      follow-up was 28 mo (interquartile range, 13-56.7 mo). The 5-y BCR-free survival
      rate was 80.5% and 69.9% in the ePLND+SNB and ePLND groups, respectively. At
      multivariate analysis, prostate-specific antigen level, primary Gleason grade
      greater than 3, seminal vesicle invasion, and higher number of removed and
      positive nodes were independent predictors of BCR in the ePLND group. In the
      ePLND+SNB group, only the number of positive nodes was an independent predictor
      of BCR. The overall accuracy of the Memorial Sloan Kettering Cancer Center
      nomogram was higher in the ePLND+SNB than in the ePLND group. However, the
      nomogram was underestimating the probability of BCR-free status in the ePLND+SNB
      group, whereas the ePLND group was performing as predicted. Conclusion: Adding
      SNB to ePLND improves BCR-free survival, although the precise explanation of this
      observation remains speculative. Our results should be interpreted cautiously,
      given the nonrandomized nature and the selection bias of the study.

PMID- 28747520
TI  - Impact of 68Ga-Prostate-Specific Membrane Antigen PET/CT on Prostate Cancer
      Management.
AB  - The objective of this study was to assess the impact of 68Ga-prostate-specific
      membrane antigen (68Ga-PSMA) PET/CT on the management of prostate cancer in
      patients with biochemical recurrence (BCR). Methods: Documented management plans
      before and after 68Ga-PSMA PET/CT in 100 patients with BCR were retrospectively
      reviewed, and changes in plans were recorded. Results: Management changed after
      68Ga-PSMA PET/CT in 39 patients (39%). The management changes occurred in 23
      (33.8%) of 68 patients with radical prostatectomy and 16 (50%) of 32 patients
      previously treated with radical radiotherapy. Positive scan results (P < 0.001)
      and higher prostate-specific antigen (PSA) levels (P = 0.024) were associated
      with management changes. No significant association with management change was
      found for Gleason grade, stage, presence of metastatic disease, PSA velocity, or
      PSA doubling time. Conclusion:68Ga-PSMA PET/CT altered management in 39% of
      patients with BCR, and changes occurred more often in patients with radical
      radiotherapy treatment, positive 68Ga-PSMA scan results, and higher PSA levels.

PMID- 28747521
TI  - Novel 18F-Labeled kappa-Opioid Receptor Antagonist as PET Radiotracer: Synthesis
      and In Vivo Evaluation of 18F-LY2459989 in Nonhuman Primates.
AB  - The kappa-opioid receptor (KOR) has been implicated in depression, addictions,
      and other central nervous system disorders and, thus, is an important target for
      drug development. We previously developed several 11C-labeled PET radiotracers
      for KOR imaging in humans. Here we report the synthesis and evaluation of 18F
      LY2459989 as the first 18F-labeled KOR antagonist radiotracer in nonhuman
      primates and its comparison with 11C-LY2459989. Methods: The novel radioligand
      18F-LY2459989 was synthesized by 18F displacement of a nitro group or an iodonium
      ylide. PET scans in rhesus monkeys were obtained on a small-animal scanner to
      assess the pharmacokinetic and in vivo binding properties of the ligand.
      Metabolite-corrected arterial activity curves were measured and used as input
      functions in the analysis of brain time-activity curves and the calculation of
      binding parameters. Results: With the iodonium ylide precursor, 18F-LY2459989 was
      prepared at high radiochemical yield (36% +/- 7% [mean +/- SD]), radiochemical
      purity (>99%), and mean molar activity (1,175 GBq/MUmol; n = 6). In monkeys, 18F
      LY2459989 was metabolized at a moderate rate, with a parent fraction of
      approximately 35% at 30 min after injection. Fast and reversible kinetics were
      observed, with a regional peak uptake time of less than 20 min. Pretreatment with
      the selective KOR antagonist LY2456302 (0.1 mg/kg) decreased the activity level
      in regions with high levels of binding to that in the cerebellum, thus
      demonstrating the binding specificity and selectivity of 18F-LY2459989 in vivo.
      Regional time-activity curves were well fitted by the multilinear analysis 1
      kinetic model to derive reliable estimates of regional distribution volumes. With
      the cerebellum as the reference region, regional binding potentials were
      calculated and ranked as follows: cingulate cortex > insula > caudate/putamen >
      frontal cortex > temporal cortex > thalamus, consistent with the reported KOR
      distribution in the monkey brain. Conclusion: The evaluation of 18F-LY2459989 in
      nonhuman primates demonstrated many attractive imaging properties: fast tissue
      kinetics, specific and selective binding to the KOR, and high specific binding
      signals. A side-by-side comparison of 18F-LY2459989 and 11C-LY2459989 indicated
      similar kinetic and binding profiles for the 2 radiotracers. Taken together, the
      results indicated that 18F-LY2459989 appears to be an excellent PET radiotracer
      for the imaging and quantification of the KOR in vivo.

PMID- 28747522
TI  - PET Imaging Stability Measurements During Simultaneous Pulsing of Aggressive MR
      Sequences on the SIGNA PET/MR System.
AB  - The recent introduction of simultaneous whole-body PET/MR scanners has enabled
      new research taking advantage of the complementary information obtainable with
      PET and MRI. One such application is kinetic modeling, which requires high levels
      of PET quantitative stability. To accomplish the required PET stability levels,
      the PET subsystem must be sufficiently isolated from the effects of MR activity.
      Performance measurements have previously been published, demonstrating sufficient
      PET stability in the presence of MR pulsing for typical clinical use; however,
      PET stability during radiofrequency (RF)-intensive and gradient-intensive
      sequences has not previously been evaluated for a clinical whole-body scanner. In
      this work, PET stability of the GE SIGNA PET/MR was examined during simultaneous
      scanning of aggressive MR pulse sequences. Methods: PET performance tests were
      acquired with MR idle and during simultaneous MR pulsing. Recent system
      improvements mitigating RF interference and gain variation were used. A fast
      recovery fast spin echo MR sequence was selected for high RF power, and an echo
      planar imaging sequence was selected for its high heat-inducing gradients.
      Measurements were performed to determine PET stability under varying MR
      conditions using the following metrics: sensitivity, scatter fraction, contrast
      recovery, uniformity, count rate performance, and image quantitation. A final PET
      quantitative stability assessment for simultaneous PET scanning during functional
      MRI studies was performed with a spiral in-and-out gradient echo sequence.
      Results: Quantitation stability of a 68Ge flood phantom was demonstrated within
      0.34%. Normalized sensitivity was stable during simultaneous scanning within
      0.3%. Scatter fraction measured with a 68Ge line source in the scatter phantom
      was stable within the range of 40.4%-40.6%. Contrast recovery and uniformity were
      comparable for PET images acquired simultaneously with multiple MR conditions.
      Peak noise equivalent count rate was 224 kcps at an effective activity
      concentration of 18.6 kBq/mL, and the count rate curves and scatter fraction
      curve were consistent for the alternating MR pulsing states. A final test
      demonstrated quantitative stability during a spiral functional MRI sequence.
      Conclusion: PET stability metrics demonstrated that PET quantitation was not
      affected during simultaneous aggressive MRI. This stability enables demanding
      applications such as kinetic modeling.

PMID- 28747523
TI  - 18F-Flortaucipir PET/MRI Correlations in Nonamnestic and Amnestic Variants of
      Alzheimer Disease.
AB  - Nonamnestic Alzheimer disease (AD) variants, including posterior cortical atrophy
      and the logopenic variant of primary progressive aphasia, differ from amnestic AD
      in distributions of tau aggregates and neurodegeneration. We evaluated whether
      18F-flortaucipir (also called 18F-AV-1451) PET, targeting tau aggregates, detects
      these differences, and we compared the results with MRI measures of gray matter
      (GM) atrophy. Methods: Five subjects with posterior cortical atrophy, 4 subjects
      with the logopenic variant of primary progressive aphasia, 6 age-matched patients
      with AD, and 6 control subjects underwent 18F-flortaucipir PET and MRI. SUV
      ratios and GM volumes were compared using regional and voxel-based methods.
      Results: The subgroups showed the expected 18F-flortaucipir-binding patterns.
      Group effect sizes were generally stronger with 18F-flortaucipir PET than with
      MRI volumes. There were moderate-to-high correlations between regional GM atrophy
      and 18F-flortaucipir uptake. 18F-flortaucipir binding and GM atrophy correlated
      similarly to cognitive test performance. Conclusion:18F-flortaucipir binding
      corresponds to the expected neurodegeneration patterns in nonamnestic AD, with
      potential for earlier detection of pathology than is possible with MRI atrophy
      measures.

PMID- 28747524
TI  - Treatment Outcomes from 68Ga-PSMA PET/CT-Informed Salvage Radiation Treatment in
      Men with Rising PSA After Radical Prostatectomy: Prognostic Value of a Negative
      PSMA PET.
AB  - 68Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men
      with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to
      triage those who will benefit from salvage radiation treatment (SRT). This study
      examines the value of PSMA-informed SRT in improving treatment outcomes in the
      context of biochemical failure after RP. Methods: We analyzed men with rising PSA
      after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for
      SRT at the time of PSMA. For each patient, clinical and pathologic features as
      well as scan results, including site of PSMA-positive disease, number of lesions,
      and a certainty score, were documented. Subsequent management, including SRT, and
      most recent PSA were recorded using medical records. Treatment response was
      defined as both PSA <= 0.1 ng/mL and >50% reduction in PSA. Multivariate logistic
      regression analysis was performed for association of clinical variables and
      treatment response to SRT. Results: One hundred sixty-four men were included.
      PSMA was positive in 62% (n = 102/164): 38 of 102 in the prostatic fossa, 41 of
      102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received
      androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In
      total, 99 of 146 received SRT with a median follow-up after radiation treatment
      of 10.5 mo (interquartile range, 6-14 mo). Overall treatment response after SRT
      was 72% (n = 71/99). Forty-five percent (n = 27/60) of patients with a negative
      PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who
      received SRT, 85% (n = 23/27) demonstrated a treatment response, compared with a
      further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients
      with disease confined to the prostate fossa on PSMA, 81% (n = 29/36) responded to
      SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% (n = 16/26)
      had treatment response after SRT. On multivariate logistic regression analysis,
      PSMA and serum PSA significantly correlated with treatment response, whereas pT
      stage, Gleason score, and surgical margin status did not. Conclusion: PSMA PET is
      independently predictive of treatment response to SRT and stratifies men into a
      high treatment response to SRT (negative or fossa-confined PSMA) versus men with
      poor response to SRT (nodes or distant-disease PSMA). In particular, a negative
      PSMA PET result predicts a high response to salvage fossa radiotherapy.

PMID- 28747525
TI  - Haemophilus spills its guts to make a biofilm.

PMID- 28747526
TI  - Clash between energy landscape theory and foldon-dependent protein folding.

PMID- 28747527
TI  - Extinction tsunami can be avoided.

PMID- 28747528
TI  - Embryo implantation evolved from an ancestral inflammatory attachment reaction.
AB  - The molecular changes that support implantation in eutherian mammals are
      necessary to establish pregnancy. In marsupials, pregnancy is relatively short,
      and although a placenta does form, it is present for only a few days before
      parturition. However, morphological changes in the uterus of marsupials at term
      mimic those that occur during implantation in humans and mice. We investigated
      the molecular similarity between term pregnancy in the marsupials and
      implantation in eutherian mammals using the gray short-tailed opossum
      (Monodelphis domestica) as a model. Transcriptomic analysis shows that term
      pregnancy in the opossum is characterized by an inflammatory response consistent
      with implantation in humans and mice. This immune response is temporally
      correlated with the loss of the eggshell, and we used immunohistochemistry to
      report that this reaction occurs at the materno-fetal interface. We demonstrate
      that key markers of implantation, including Heparin binding EGF-like growth
      factor and Mucin 1, exhibit expression and localization profiles consistent with
      the pattern observed during implantation in eutherian mammals. Finally, we show
      that there are transcriptome-wide similarities between the opossum attachment
      reaction and implantation in rabbits and humans. Our data suggest that the
      implantation reaction that occurs in eutherians is derived from an attachment
      reaction in the ancestral therian mammal which, in the opossum, leads directly to
      parturition. Finally, we argue that the ability to shift from an inflammatory
      attachment reaction to a noninflammatory period of pregnancy was a key innovation
      in eutherian mammals that allowed an extended period of intimate placentation.

PMID- 28747529
TI  - Detection and quantification of inbreeding depression for complex traits from SNP
      data.
AB  - Quantifying the effects of inbreeding is critical to characterizing the genetic
      architecture of complex traits. This study highlights through theory and
      simulations the strengths and shortcomings of three SNP-based inbreeding measures
      commonly used to estimate inbreeding depression (ID). We demonstrate that
      heterogeneity in linkage disequilibrium (LD) between causal variants and SNPs
      biases ID estimates, and we develop an approach to correct this bias using LD and
      minor allele frequency stratified inference (LDMS). We quantified ID in 25 traits
      measured in [Formula: see text] participants of the UK Biobank, using LDMS, and
      confirmed previously published ID for 4 traits. We find unique evidence of ID for
      handgrip strength, waist/hip ratio, and visual and auditory acuity (ID between 
      2.3 and -5.2 phenotypic SDs for complete inbreeding; [Formula: see text]). Our
      results illustrate that a careful choice of the measure of inbreeding combined
      with LDMS stratification improves both detection and quantification of ID using
      SNP data.

PMID- 28747530
TI  - Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation
      of VRC01-class HIV-1 broadly neutralizing antibodies.
AB  - Variable regions of Ig chains provide the antigen recognition portion of B-cell
      receptors and derivative antibodies. Ig heavy-chain variable region exons are
      assembled developmentally from V, D, J gene segments. Each variable region
      contains three antigen-contacting complementarity-determining regions (CDRs),
      with CDR1 and CDR2 encoded by the V segment and CDR3 encoded by the V(D)J
      junction region. Antigen-stimulated germinal center (GC) B cells undergo somatic
      hypermutation (SHM) of V(D)J exons followed by selection for SHMs that increase
      antigen-binding affinity. Some HIV-1-infected human subjects develop broadly
      neutralizing antibodies (bnAbs), such as the potent VRC01-class bnAbs, that
      neutralize diverse HIV-1 strains. Mature VRC01-class bnAbs, including VRC-PG04,
      accumulate very high SHM levels, a property that hinders development of vaccine
      strategies to elicit them. Because many VRC01-class bnAb SHMs are not required
      for broad neutralization, high overall SHM may be required to achieve certain
      functional SHMs. To elucidate such requirements, we used a V(D)J passenger allele
      system to assay, in mouse GC B cells, sequence-intrinsic SHM-targeting rates of
      nucleotides across substrates representing maturation stages of human VRC-PG04.
      We identify rate-limiting SHM positions for VRC-PG04 maturation, as well as SHM
      hotspots and intrinsically frequent deletions associated with SHM. We find that
      mature VRC-PG04 has low SHM capability due to hotspot saturation but also
      demonstrate that generation of new SHM hotspots and saturation of existing
      hotspot regions (e.g., CDR3) does not majorly influence intrinsic SHM in
      unmutated portions of VRC-PG04 progenitor sequences. We discuss implications of
      our findings for bnAb affinity maturation mechanisms.

PMID- 28747531
TI  - Remarkable size-spectra stability in a marine system undergoing massive invasion.
AB  - The Mediterranean Sea is an invasion hotspot, with non-indigenous species
      suspected to be a major driver behind community changes. We used size spectra, a
      reliable index of food web structure, to examine how the influx of Red Sea fishes
      into the Mediterranean Sea has impacted the indigenous species community. This is
      the first attempt to use changes in the size spectra to reveal the effect of
      biological invasions. We used data from trawl catches along Israel's shoreline
      spanning 20 years to estimate changes in the community size spectra of both
      indigenous and non-indigenous species. We found that the relative biomass of non
      indigenous species increased over the 20 years, especially for small and large
      species, leading to a convergence with the indigenous species size spectra.
      Hence, the biomass of indigenous and non-indigenous species has become identical
      for all size classes, suggesting similar energetic constraints and sensitivities
      to fishing. However, over this time period the size spectrum of indigenous
      species has remained remarkably constant. This suggests that the wide-scale
      invasion of non-indigenous species into the Mediterranean may have had little
      impact on the community structure of indigenous species.

PMID- 28747532
TI  - Negative phenotypic and genetic correlation between natal dispersal propensity
      and nest-defence behaviour in a wild bird.
AB  - Natural selection is expected to favour the integration of dispersal and
      phenotypic traits allowing individuals to reduce dispersal costs. Accordingly,
      associations have been found between dispersal and personality traits such as
      aggressiveness and exploration, which may facilitate settlement in a novel
      environment. However, the determinism of these associations has only rarely been
      explored. Here, we highlight the functional integration of individual personality
      in nest-defence behaviour and natal dispersal propensity in a long-lived colonial
      bird, the Alpine swift (Apus melba), providing insights into genetic constraints
      shaping the coevolution of these two traits. We report a negative association
      between natal dispersal and nest-defence (i.e. risk taking) behaviour at both the
      phenotypic and genetic level. This negative association may result from direct
      selection if risk-averseness benefits natal dispersers by reducing the costs of
      settlement in an unfamiliar environment, or from indirect selection if
      individuals with lower levels of nest defence also show lower levels of
      aggressiveness, reducing costs of settlement among unfamiliar neighbours in a
      colony. In both cases, these results highlight that risk taking is an important
      behavioural trait to consider in the study of dispersal evolution.

PMID- 28747533
TI  - Species integrity enhanced by a predation cost to hybrids in the wild.
AB  - Species integrity can be challenged, and even eroded, if closely related species
      can hybridize and produce fertile offspring of comparable fitness to that of
      parental species. The maintenance of newly diverged or closely related species
      therefore hinges on the establishment and effectiveness of pre- and/or post
      zygotic reproductive barriers. Ecological selection, including predation, is
      often presumed to contribute to reduced hybrid fitness, but field evidence for a
      predation cost to hybridization remains elusive. Here we provide proof-of-concept
      for predation on hybrids being a postzygotic barrier to gene flow in the wild.
      Cyprinid fishes commonly produce fertile, viable hybrid offspring and therefore
      make excellent study organisms to investigate ecological costs to hybrids. We
      electronically tagged two freshwater cyprinid fish species (roach Rutilus rutilus
      and bream Abramis brama) and their hybrids in 2005. Tagged fish were returned to
      their lake of origin, exposing them to natural predation risk from apex avian
      predators (great cormorant, Phalacrocorax carbo). Scanning for regurgitated tags
      under cormorant roosts 3-4 years later identified cormorant-killed individual
      fish and allowed us to directly test for a predation cost to hybrids in the wild.
      Hybrid individuals were found significantly more susceptible to cormorant
      predation than individuals from either parental species. Such ecological
      selection against hybrids contributes to species integrity, and can enhance
      species diversification.

PMID- 28747534
TI  - Heartbeat: New insights in congenital heart disease.

PMID- 28747535
TI  - Palliative care in end-stage valvular heart disease.
AB  - Valvular heart disease (VHD), particularly aortic valve disease, is prevalent
      with increasing incidence. When surgery is not possible, or when risks outweigh
      benefits, percutaneous treatment options may offer effective alternatives.
      However, procedures may not always go as planned, and frail patients or those
      whose symptoms are caused by other comorbidities may not benefit from valve
      intervention at all. Significant effort should be made to assess frailty,
      comorbidities and patient goals prior to intervention. Palliative care (PC)
      should play a critical role in the care of patients with severe valve disease. PC
      is specialised medical care that aims to optimise health-related quality of life
      by managing symptoms and clarifying patient values and goals of care. It should
      be implemented at the time of diagnosis and continue throughout the disease
      course. Because of the paucity of studies dedicated to the provision of PC to
      patients with advanced VHD, further research is needed.

PMID- 28747536
TI  - Identification of adult cardiac arrest using NHS Pathways.

PMID- 28747537
TI  - John Sculley's Noble Cause: Disruptive Innovation to Transform Healthcare.

PMID- 28747538
TI  - Complexing Agents and pH Influence on Chemical Durability of Type I Molded Glass
      Containers.
AB  - Among the factors that affect the glass surface chemical durability, pH and
      complexing agents present in aqueous solution have the main role. Glass surface
      attack can be also related to the delamination issue causing glass particles'
      appearance in the pharmaceutical preparation. A few methods to check for glass
      containers delamination propensity and some control guidelines have been
      proposed. The present study emphasizes the possible synergy between a few
      complexing agents with pH on borosilicate glass chemical durability.Hydrolytic
      attack was performed in small-volume 23 mL type I glass containers autoclaved
      according to the European Pharmacopoeia or United States Pharmacopeia for 1 h at
      121  degrees C, in order to enhance the chemical attack due to time, temperature,
      and the unfavorable surface/volume ratio. Solutions of 0.048 M or 0.024 M (M/L)
      of the acids citric, glutaric, acetic, EDTA (ethylenediaminetetraacetic acid),
      together with sodium phosphate with water for comparison, were used for the
      trials. The pH was adjusted +/-0.05 units at fixed values 5.5, 6.6, 7, 7.4, 8,
      and 9 by LiOH diluted solution.Because silicon is the main glass network former,
      silicon release into the attack solutions was chosen as the main index of the
      glass surface attack and analysed by inductively coupled plasma atomic emission
      spectrophotometry. The work was completed by the analysis of the silicon release
      in the worst attack conditions of molded glass, soda lime type II glass, and
      tubing borosilicate glass vials to compare different glass compositions and
      forming technologies. Surface analysis by scanning electron microscopy was
      finally performed to check for the surface status after the worst chemical attack
      condition by citric acid.LAY ABSTRACT: Glass, like every packaging material, can
      have some usage limits, mainly in basic pH solutions. The issue of glass surface
      degradation particles that appear in vials (delamination) has forced a number of
      drug product recalls in recent years. To prevent such situations, pharmaceutical
      and biopharmaceutical manufacturers need to understand the reasons for accelerate
      surface glass corrosion mainly in the case of injectables.Some drugs can contain
      active components with known ability to corrode glass silica networks. Sometimes
      these ingredients are dissolved in an alkaline medium that dramatically increases
      the glass corrosion and potentially causes the issue. As this action is strongly
      affected by time and temperature, flaking may become visible only after a long
      storage time. The purpose of this investigation is to verify the borosilicate
      glass chemical durability during controlled conditions of time and temperature
      when in contact with testing solutions containing different complexing agents by
      varying the pH. Si concentration in the extract solution is taken as an index of
      glass dissolution during constant autoclaving conditions for 1 h at 121  degrees
      C, which simulates approximately five years of contact at room
      temperature.Acetate, citrate, ethylenediaminetetraacetic acid (EDTA), phosphate,
      and glutarate 0.048 M or 0.024 M solutions were used at increasing pH from 5.5 to
      9.0. The chemical durability of two borosilicate tubing glass vials of different
      glass compositions were compared with the molded one in the worst attack
      conditions by citric acid. Even if no delamination issue has been experienced by
      this study in type I molded and tubing containers, the conclusions developed can
      provide pharmaceutical manufacturers with useful information to prevent glass
      delamination risk in their processes.

PMID- 28747539
TI  - Steroidogenesis in Leydig cells: effects of aging and environmental factors.
AB  - Serum testosterone (TS) levels decrease with aging in both humans and rodents.
      Using the rat as a model system, it was found that age-related reductions in
      serum TS were not due to loss of Leydig cells, but rather to the reduced ability
      of the Leydig cells to produce TS in response to luteinizing hormone (LH).
      Detailed analyses of the steroidogenic pathway have suggested that two defects
      along the pathway, LH-stimulated cAMP production and cholesterol transport to and
      into the mitochondria, are of particular importance in age-related reductions in
      TS production. Although the mechanisms involved in these defects are far from
      certain, increasing oxidative stress appears to play a particularly important
      role. Interestingly, increased oxidative stress also appears to be involved in
      the suppressive effects of endocrine disruptors on Leydig cell TS production.

PMID- 28747541
TI  - Obesity, a serious etiologic factor for male subfertility in modern society.
AB  - Obesity, defined as excessive accumulation of fat in adipose tissue, is a
      metabolic disorder resulting from behavioral, environmental and heritable causes.
      Obesity increases the risks of hypertension, diabetes, cardiovascular disease,
      sleep apnea, respiratory problems, osteoarthritis and cancer. Meanwhile, the
      negative impact of obesity on male reproduction is gradually recognized.
      According to the clinical investigations and animal experiments, obesity is
      correlated with reductions in sperm concentration and motility, increase in sperm
      DNA damage and changes in reproductive hormones. Several mechanisms can elucidate
      the effects of obesity on sperm functions and male subfertility, i.e., the
      excessive conversion of androgens into estrogens in redundant adipose tissue
      causes sexual hormone imbalance, subsequently resulting in hypogonadism.
      Secondly, adipokines produced by adipose tissue induce severe inflammation and
      oxidative stress in male reproductive tract, directly impairing testicular and
      epididymal tissues. Moreover, increased scrotal adiposity leads to increase
      gonadal heat, continuously hurting spermatogenesis. Therefore, obesity alters the
      systematic and regional environment crucial for spermatogenesis in testis and
      sperm maturation in epididymis, and finally results in poor sperm quality
      including decreased sperm motility, abnormal sperm morphology and acrosome
      reaction, changed membrane lipids and increased DNA damage. Furthermore, recent
      studies indicate that epigenetic changes may be a consequence of increased
      adiposity. A major effort to identify epigenetic determinants of obesity revealed
      that sperm DNA methylation and non-coding RNA modification are associated with
      BMI changes and proposed to inherit metabolic comorbidities across generations.
      This review will explain how obesity-related changes in males to influence sperm
      function and male fertility as well.

PMID- 28747540
TI  - Chronicling the discovery of interferon tau.
AB  - It has been 38 years since a protein, now known as interferon tau (IFNT), was
      discovered in ovine conceptus-conditioned culture medium. After 1979,
      purification and testing of native IFNT revealed its unique antiluteolyic
      activity to prevent the regression of corpora lutea on ovaries of nonpregnant
      ewes. Antiviral, antiproliferative and immunomodulatory properties of native and
      recombinant IFNT were demonstrated later. In addition, progesterone and IFNT were
      found to act cooperatively to silence expression of classical interferon
      stimulated genes in a cell-specific manner in ovine uterine luminal and
      superficial glandular epithelia. But, IFNT signaling through a STAT1/STAT2
      independent pathway stimulates expression of genes, such as those for transport
      of glucose and amino acids, which are required for growth and development of the
      conceptus. Further, undefined mechanisms of action of IFNT are key to a
      servomechanism that allows ovine placental lactogen and placental growth hormone
      to affect the development of uterine glands and their expression of genes
      throughout gestation. IFNT also acts systemically to induce the expression of
      interferon stimulated genes that influence secretion of progesterone by the
      corpus luteum. Finally, IFNT has great potential as a therapeutic agent due to
      its low cytotoxicity, anti-inflammatory properties and effects to mitigate
      diabetes, obesity-associated syndromes and various autoimmune diseases.

PMID- 28747582
TI  - An improved genetic algorithm for designing optimal temporal patterns of neural
      stimulation.
AB  - OBJECTIVE: Electrical neuromodulation therapies typically apply constant
      frequency stimulation, but non-regular temporal patterns of stimulation may be
      more effective and more efficient. However, the design space for temporal
      patterns is exceedingly large, and model-based optimization is required for
      pattern design. We designed and implemented a modified genetic algorithm (GA)
      intended for design optimal temporal patterns of electrical neuromodulation.
      APPROACH: We tested and modified standard GA methods for application to designing
      temporal patterns of neural stimulation. We evaluated each modification
      individually and all modifications collectively by comparing performance to the
      standard GA across three test functions and two biophysically-based models of
      neural stimulation. MAIN RESULTS: The proposed modifications of the GA
      significantly improved performance across the test functions and performed best
      when all were used collectively. The standard GA found patterns that outperformed
      fixed-frequency, clinically-standard patterns in biophysically-based models of
      neural stimulation, but the modified GA, in many fewer iterations, consistently
      converged to higher-scoring, non-regular patterns of stimulation. SIGNIFICANCE:
      The proposed improvements to standard GA methodology reduced the number of
      iterations required for convergence and identified superior solutions.

PMID- 28747583
TI  - Plasmonic gold nanostars as optical nano-additives for injection molded polymer
      composites.
AB  - Nanoscale engineering of noble metal particles has provided numerous material
      configurations to selectively confine and manipulate light across the
      electromagnetic spectrum. Transitioning these materials to a composite form while
      maintaining the desired resonance properties has proven challenging. In this
      work, the successful integration of plasmon-focusing gold nanostars (GNSs) into
      polymer nanocomposites (PNCs) is demonstrated. Tailored GNSs are produced with
      over a 90% yield and methods to control the branching structures are shown. A
      protective silica capping shell is employed on the nanomaterials to facilitate
      survivability in the high temperate/high shear processing parameters to create
      optically-tuned injection molded PNCs. The developed GNS PNCs possess dichroic
      scattering and absorption behavior, opening up potential applications in the
      fields of holographic imaging, optical filtering and photovoltaics.

PMID- 28747584
TI  - Codon optimization enables the Zeocin resistance marker's use in the ascomycete
      yeast Debaryomyces occidentalis.

PMID- 28747585
TI  - Amylolytic fungi in starter cakes for rice beer production.
AB  - Two types of starter cakes, viz. amou and perok-kushi, used in the production of
      rice beer in Assam, India, by the Bodo and Deori communities, respectively, were
      used for the isolation of amylolytic fungi. Based on the sequencing of their
      internal transcribed spacer (ITS) regions the fungi were identified as Amylomyces
      rouxii and Rhizopus oryzae, and given the strain names TU460 and TU465,
      respectively. Both the strains showed the ability to degrade and saccharify
      starch. The glucoamylase activity was considerably high in A. rouxii TU460 (14.92
      MUmol/min) as compared to R. oryzae TU465 (1.41 MUmol/min), whereas alpha-amylase
      activity was found to be closely related, i.e. 7.02 and 6.09 unit mL-1,
      respectively. SDS PAGE for the determination of the molecular size of the
      glucoamylase enzymes revealed the production of two distinct units of 59 kDa and
      31 kDa by A. rouxii TU460, and one unit of 72 kDa by R. oryzae TU465. LC MS/MS
      analysis revealed that no mycotoxins were produced by either of the strains. The
      overall study indicated a good amylolytic property of both strains and a
      potential for application in the starch processing industries.

PMID- 28747586
TI  - A novel probiotic Bacillus siamensis B44v isolated from Thai pickled vegetables
      (Phak-dong) for potential use as a feed supplement in aquaculture.
AB  - The use of probiotic bacteria to control bacterial infection in farmed fish is of
      clear practical interest. The aims of this study were to isolate and select a
      probiotic Bacillus sp. and to evaluate the effects of its supplementation on the
      growth and disease resistance of hybrid catfish. Bacillus siamensis strain B44v,
      selectively isolated from Thai pickled vegetables (Phak-dong), displayed a high
      potential as a probiotic in catfish culture. This bacterium produced a
      bacteriocin-like substance and exhibited a broad-spectrum antibacterial activity
      inhibiting both Gram-positive and Gram-negative bacteria, especially the fish
      pathogens Aeromonas hydrophila and Streptococcus agalactiae. The susceptibility
      to all 14 antibiotics tested implies its less possibility to be the antibiotic
      resistant bacterium. Bacillus siamensis strain B44v possessed interesting
      adhesion properties, as shown by its high percentages of hydrophobicity (64.8%),
      auto-agglutination (73.8%), co-aggregation (67.2% with A. hydrophila FW52 and
      63.5% with S. agalactiae F3S), and mucin binding (88.7%). The strain B44v
      survived simulated gastrointestinal conditions and produced protease and
      cellulase enzymes. Hybrid catfish (C. macrocephalus * C. gariepinus) were
      employed in the feed-trial experiments. Fish fed diet containing strain B44v (107
      CFU/g feed) displayed not only no mortality but also growth improvement. At the
      end of the feed trial, fish were challenged by an intraperitoneal injection of
      Aeromonas hydrophila FW52. The Bacillus siamensis strain B44v fed fish survived
      (75.0%; p < 0.05) better than the controls (36.7%; p < 0.05) after a two week
      challenge. These collective results present for the first time the potential of
      Bacillus siamensis strain B44v for use as a bacterial probiotic in aquaculture.

PMID- 28747587
TI  - Distribution of Diverse Escherichia coli between Cattle and Pasture.
AB  - Escherichia coli is widely considered to not survive for extended periods outside
      the intestines of warm-blooded animals; however, recent studies demonstrated that
      E. coli strains maintain populations in soil and water without any known fecal
      contamination. The objective of this study was to investigate whether the niche
      partitioning of E. coli occurs between cattle and their pasture. We attempted to
      clarify whether E. coli from bovine feces differs phenotypically and
      genotypically from isolates maintaining a population in pasture soil over winter.
      Soil, bovine fecal, and run-off samples were collected before and after the
      introduction of cattle to the pasture. Isolates (363) were genotyped by uidA and
      mutS sequences and phylogrouping, and evaluated for curli formation (Rough, Dry,
      And Red, or RDAR). Three types of clusters emerged, viz. bovine-associated,
      clusters devoid of cattle isolates and representing isolates endemic to the
      pasture environment, and clusters with both. All isolates clustered with strains
      of E. coli sensu stricto, distinct from the cryptic species Clades I, III, IV,
      and V. Pasture soil endemic and bovine fecal populations had very different
      phylogroup distributions, indicating niche partitioning. The soil endemic
      population was largely comprised of phylogroup B1 and had a higher average RDAR
      score than other isolates. These results indicate the existence of environmental
      E. coli strains that are phylogenetically distinct from bovine fecal isolates,
      and that have the ability to maintain populations in the soil environment.

PMID- 28747588
TI  - Surgical Site Infection after Malignant Brain Tumor Resection: A Multicenter
      Study for Induction of a Basic Care Bundle.
AB  - Patients with malignant brain tumors are possibly at increased risk for surgical
      site infections (SSIs) considering the various medical situations associated with
      the disease. However, the actual rate of SSI after malignant brain tumor
      resection has not been well established, despite the potential impact of SSI on
      patient outcome. To investigate the incidence of SSI following malignant brain
      tumor surgery, we performed a retrospective study in 3 neurosurgical units.
      Subsequently, aiming at the reduction of incidence of SSI, we performed a
      prospective study using a care bundle technique in the same units. The SSI
      incidence in the retrospective (n = 161) and prospective studies (n = 68) were
      4.3% and 4.4%, respectively, similar to the previously reports on general
      craniotomies. A care bundle does not appear to enhance prevention of SSI.
      However, future, large studies with a new care bundle should be planned based on
      a zero tolerance policy.

PMID- 28747589
TI  - What Is the Most Representative Parameter for Describing the Size of the Atlas?
      CT Morphometric Analysis of the Atlas with Special Reference to Atlas Hypoplasia.
AB  - The spinal canal diameter (SCD) is one of the most studied factors for the
      assessment of cervical spinal canal stenosis. The inner anteroposterior diameter
      (IAP), the SCD, and the cross-sectional area (CSA) of the atlas have been used
      for the evaluation of the size of the atlas in patients with atlas hypoplasia, a
      rare form of developmental spinal canal stenosis, however, there is little
      information on their relationship. The aim of this study was to identify the most
      useful parameter for depicting the size of the atlas. The CSA, the IAP, and the
      SCD were measured on computed tomography (CT) images at the C1 level of 213
      patients and compared in this retrospective study. These three parameters
      increased with increasing patient height and weight. There was a strong
      correlation between IAP and SCD (r = 0.853) or CSA (r = 0.822), while correlation
      between SCD and CSA (r = 0.695) was weaker than between IAP and CSA. Partial
      correlation analysis showed that IAP was positively correlated with SCD (r =
      0.687) and CSA (r = 0.612) when CSA or SCD were controlled. SCD was negatively
      correlated with CSA when IAP was controlled (r = -0.21). The IAP can serve as the
      CSA for the evaluation of the size of the atlas ring, while the SCD does not
      correlate with the CSA. As the patient height and weight affect the size of the
      atlas, analysis of the spinal canal at the C1 level should take into account
      physiologic patient data.

PMID- 28747590
TI  - Self-reported Sleep Duration and Subclinical Atherosclerosis in a General
      Population of Japanese Men.
AB  - AIM: There are few data regarding associations between sleep duration and
      subclinical atherosclerosis in Japan. The aim of this study was to evaluate
      associations of self-reported sleep duration with calcification in the coronary
      arteries (CAC) and carotid intima media thickness (IMT) in Japanese men. METHODS:
      This was a cross-sectional survey of 1093 randomly selected men from Kusatsu
      City, Japan. Average sleep duration on weekdays was estimated through
      questionnaire; CAC by computed tomography; and carotid IMT by ultrasonography.
      RESULTS: The prevalence of CAC was 50.0% for participants with sleep duration
      <5.5 h, 43.9% with 5.5-6.4 h, 50.0% with 6.5-7.4 h, 49.3% with 7.5-8.4 h, and
      62.5% with >=8.5 h. In univariate analysis, participants with sleep duration
      >=8.5 h had significantly higher prevalence of CAC than those with 6.5-7.4 h
      (p=0.043). After adjustment for age and other risk factors, however, the
      association was not significant (p=0.776). The average IMT was 0.85 mm for
      participants with sleep duration <5.5 h, 0.83 mm with 5.5-6.4 h, 0.85 mm with 6.5
      7.4 h, 0.88 mm with 7.5-8.4 h, and 0.90 mm with >=8.5 h. None of the differences
      in IMT observed in crude or multivariable-adjusted analyses was significant (all
      p>0.1). CONCLUSION: Self-reported sleep duration was not associated with
      increased CAC or carotid IMT in a general population of Japanese men.

PMID- 28747591
TI  - Assessment of Genetic and Chemical Variability in Curcumae Longae Rhizoma
      (Curcuma longa) Based on DNA Barcoding Markers and HPLC Fingerprints.
AB  - Curcumae Longae Rhizoma (Curcuma longa L.) is an important traditional Chinese
      medicine with multiple beneficial effects. To elucidate the genetic and chemical
      differences among Curcumae Longae Rhizoma samples, three DNA barcoding markers
      (rbcL, matK, and ITS-LSU D1/D3) and HPLC fingerprinting were employed in this
      study. The discriminatory power of rbcL and matK was low, as they only detected
      one sequence type that showed 100% similarity with more than 20 congeneric
      species in the Barcode of Life Data Systems (BOLD) database. In contrast, ITS-LSU
      D1/D3 showed sufficient discriminatory power to precisely identify all of the
      market samples as C. longa L. in a BLAST search as well as differentiate each
      sample based on 2-10 ITS-LSU D1/D3 haplotypes with intragenomic variability (mean
      p-distance: 0.7%, range: 0-2.6%; mean number of differences: 9.6 sites, range: 0
      38 sites). HPLC fingerprinting of 13 commercial samples showed a similarity that
      ranged from 0.769 to 0.996, indicating that the sample quality varied. A cluster
      analysis based on 5 common peak areas from the HPLC chromatogram resulted in two
      groups. Group I included 9 samples with a relatively high chemical content, and
      group II contained 4 samples with a low chemical content. A Mantel test revealed
      a low correlation (r=0.1721, p=0.047) between genetic and chemical differences.
      Our findings suggest that the integrated approach of ITS-LSU D1/D3 DNA barcoding
      and HPLC fingerprinting provides a comprehensive, precise, and convenient method
      to clarify the genetic and chemical differences in Curcumae Longae Rhizoma.

PMID- 28747592
TI  - Investigation of spinal nerve ligation-mediated functional activation of the rat
      brain using manganese-enhanced MRI.
AB  - To provide clear information on the cerebral regions according to peripheral
      neuropathy, the functional activation was investigated using manganese-enhanced
      magnetic resonance imaging (MEMRI). L5-spinal nerve ligation (SNL) was applied to
      the rats to induce neuropathic pain. Mechanical allodynia and thermal
      hyperalgesia were measured to confirm neuropathic pain induction following before
      and after gabapentin (GBP) treatment. The cerebral regions were investigated
      using a 4.7T MRI system in the sham, SNL, and GBP-treated SNL rats. Neuropathic
      pain was severely induced by SNL on the postoperative day 14, excepting the sham
      group. While MEMRI indicated many activation regions in the brain of SNL rats
      before GBP treatment, the activities were chronologically attenuated after GBP
      treatment. The brain regions relating SNL-induced neuropathic pain were as
      follows: the posterior association area of the parietal region, superior
      colliculus, inferior colliculus, primary somatosensory area, cingulate cortex,
      and cingulum bundle. SNL induced- neuropathic pain is transmitted to the primary
      somatosensory area and parietal region through the cingulum bundle and limbic
      system. These findings would be helpful for the understanding of neuropathic pain
      associated process and be an accurate target for a relief of neuropathic pain.

PMID- 28747593
TI  - Feeding Support Team for Frail, Disabled, or Elderly People during the Early
      Phase of a Disaster.
AB  - Japan was struck by two catastrophic disasters on March 11, 2011 and on April 16,
      2016. The former was the Great East Japan Earthquake (M9.0) and the latter was
      the Kumamoto Earthquake (M7.0). Most inhabitants in the affected areas of both
      disasters were forced to live in evacuation centers right after the earthquake.
      Poor oral hygiene, inactivity, malnourishment, appetite loss, eating problems,
      and swallowing problems due to lack of support for frail, disabled, or elderly
      evacuees occur during the early phases after a disaster. Disaster-related
      sequelae, such as pneumonia and disuse syndrome, may also occur as a result of
      inappropriate nutritional and physical support. Adequate oral intake and physical
      activity are important to the quality of life for evacuees. We learned lessons
      from our experiences of evacuee support after the two disasters, focused on
      feeding support, which consisted of nutritional and physical care. Our
      experiences revealed that more rapid intervention is necessary, particularly for
      frail, disabled, or elderly people. In this study, based on our experiences from
      the two dreadful disasters in Japan, we propose a new concept of medical
      assistance after a disaster, the Disaster Feeding Support Team (D-FST). The D-FST
      is composed of multidisciplinary professionals and provides comprehensive
      nutritional, physical, and health support. The D-FST also performs interventions
      for swallowing exercises, activity, health condition, and cognition that are
      related to eating circumstances. We suggest that D-FSTs are organized nationwide
      and initiate support activities immediately after the onset of a disaster.

PMID- 28747594
TI  - Mechanical and biological effects of infiltration with biopolymers on 3D printed
      tricalciumphosphate scaffolds.
AB  - The aim of this study was to evaluate the influence of infiltrating 3D printed
      (TCP) scaffolds with different biodegradable polymers on their mechanical and
      biological properties. 3D printed TCP scaffolds with interconnecting channels
      measuring 450+/-50 um were infiltrated with four different biodegradable
      copolymers. To determine the average compressive strength, a uniaxial testing
      system was used. Additionally, scaffolds were seeded with MC3T3 cells and cell
      viability was assessed by live/dead-assay. Uninfiltrated TCP had an average
      compression strength of 1.92+/-0.38 MPa. Mechanical stability was considerably
      increased in all infiltrated scaffolds up to a maximum of 7.36+/-0.57 MPa. All
      scaffolds demonstrated high cell survival rates with a maximum of 94+/-10 %
      living cells. In conclusion, infiltration of 3D printed tricalcium phosphate
      scaffolds with biodegradable polymers significantly improved mechanical
      properties and biological properties were comparable to those of uninfiltrated
      TCP scaffolds.

PMID- 28747595
TI  - NAC ameliorates dental composite-induced DNA double-strand breaks and chromatin
      condensation.
AB  - Released (co)monomers from dental composite components can induce DNA damage of
      which DNA double-strand breaks (DSBs) threaten genome integrity. Here, we tested
      whether the administration of the antioxidant N-acetylcysteine (NAC) is able to
      reduce the dental composite-induced DSBs in primary human gingiva fibroblasts.
      The dental composites Bis-GMA (bisphenol-A-glycerolate dimethacrylate), GMA
      (glycidyl methacrylate), HEMA (2-hydroxyethyl methacrylate) and TEGDMA
      (triethyleneglycol dimethacrylate) were found to induce co-localizing microscopic
      nuclear foci numbers of the DSB markers gamma-H2AX and 53BP1 per cell in the
      order: GMA>Bis-GMA>TEGDMA>HEMA. Supplementation of (co)monomer-containing culture
      medium with NAC led to a significant reduction of resin-induced DSBs as well as
      to an amelioration of dental monomer-induced nuclear chromatin condensation in
      gingival fibroblasts. Thus, antioxidant treatment can reduce radical-induced
      chromatin and DNA damage and open avenues to mitigate genotoxic effects of dental
      composite compounds.

PMID- 28747596
TI  - Intraoral electric potential via oral bacterial power generation -A novel
      mechanism of biofilm formation.
AB  - In the early stages of biofilm accumulation, the electric charge of the dental
      enamel and pellicle surfaces is known to be involved. We therefore investigated
      the relationship between oral hygiene and intraoral electric potential (IoP) in
      45 male participants using a double-blind study. IoP, but not body surface
      electric potential, was loosely correlated with oral hygiene condition (Oral
      Hygiene Index; OHI). IoP was also loosely correlated with smartphone use;
      however, there was no significant correlation between smartphone use and OHI. IoP
      elevation might be caused by OHI elevation resulting from biofilm formation as an
      internal factor, with smartphone use as an external factor. This in vitro study
      revealed the generating capacity of Streptococcus mutans accompanied by biofilm
      accumulation using a microbial fuel cell. These results suggest that IoP
      elevation is caused by biofilm accumulation induced by power generation of oral
      bacteria, resulting in elevation of OHI.

PMID- 28747597
TI  - Antimicrobial activity of ethylene-vinyl acetate containing bioactive filler
      against oral bacteria.
AB  - We developed an ethylene vinyl acetate (EVA) containing surface pre-reacted glass
      ionomer (S-PRG) filler, as a new mouthguard material for preventing intraoral
      bacterial infection. We examined its physical properties, antimicrobial activity
      against a major cariogenic bacterium Streptococcus mutans and a
      periodontopathogen Porphyromonas gingivalis, and its cytotoxicity toward human
      gingival epithelial cells. S-PRG filler was added to EVA copolymer at 5, 10, 20,
      or 40 wt% and was processed into disc-shaped test specimens. Only minor
      differences between the Shore hardness and rebound resilience properties of EVA
      materials with and without the S-PRG filler were observed. The specimens with S
      PRG filler showed bacteriostatic activity toward S. mutans and P. gingivalis and
      inhibited S. mutans biofilm formation. No cytotoxicity against the gingival
      epithelial cells was observed. Our findings show that EVA containing S-PRG filler
      has antimicrobial activity toward pathogenic oral bacteria and may be an
      effective material for maintaining the oral health of athletes.

PMID- 28747598
TI  - The effect of crude drugs on the angiogenic property and dynamic viscoelasticity
      of PEMA-based soft polymer materials.
AB  - This study aimed to determine the effect of crude drugs on the dynamic
      viscoelasticity and angiogenic property of soft polymer materials, in vitro. Two
      kinds of polyethyl methacrylates, and crude drugs (Astragalus membranaceus Bunge
      [HQ] and Salvia miltiorrhiza Bunge [DS]) were used in their powdered forms. And,
      acetyl tributyl citrate and ethyl alcohol were used in the liquid form. The
      dynamic viscoelasticity of each specimen was measured after 0, 1, 3, 7, 14 and 28
      days of immersion in distilled water. The CellPlayer angiogenesis PrimeKit assay
      was used to test angiogenesis. Significant differences in dynamic viscoelasticity
      were observed among the materials. Specimens containing 1 wt% HQ showed higher
      angiogenic activity than those containing 5 wt% and 10 wt% HQ, and DS. Our
      results suggest that the addition of low amounts of crude drugs to soft polymer
      materials may promote angiogenesis in human tissues.

PMID- 28747599
TI  - Interstitial pneumonia with autoimmune features.
AB  - Some patients with idiopathic interstitial pneumonias (IIPs) have clinical
      features that suggest autoimmune process but not fulfill established criteria for
      connective tissue disease (CTD). Different terms and criteria have been proposed
      to describe these patients, which includes undifferentiated connective tissue
      disease (UCTD), lung dominant connective tissue disease (LD-CTD), and autoimmune
      featured interstitial lung disease (AIF-ILD). To marshal these ununiform
      classification criteria, the "European Respiratory Society/American Thoracic
      Society Task Force on Undifferentiated Forms of Connective Tissue Disease
      associated Interstitial Lung Disease" proposed a consensus regarding the
      nomenclature and classification criteria for patients with IIP and features of
      autoimmunity with the term "interstitial pneumonia with autoimmune features"
      (IPAF). It was reported that patients with IPAF accounted for 7.3%~34.1% of
      patients with interstitial lung disease (ILD). Survival, rate of progressing to
      CTD, appropriate treatment, and treatment response are not yet elucidated.
      Furthermore, it is not determined whether IPAF is a distinct category of ILD or
      simply a part of IIP. These questions should be elucidated by future prospective
      cohort studies. Hopefully, rheumatologists should participate in not only
      clinical trials but also in multidisciplinary discussions for IPAF.

PMID- 28747600
TI  - Severe combined immunodeficiency: From its discovery to the perspective.
AB  - Severe combined immunodeficiency (SCID) is impaired in lymphocyte development and
      function. Affected children have extreme susceptibility to infections, which are
      fatal in the first year of life without treatment. The estimate of incidence is
      one in approximately 50,000 live birth. The first series of diseases were
      described in 1950s, and all patients died in infancy. The first transplant for
      SCID was carried out in 1968, and it has been described that SCID patients could
      be treated by hematopoietic stem cell transplantation (HSCT) since then.
      Adenosine deaminase and common gamma chain were identified to be causative genes
      for SCID in 1972 and 1993, respectively. SCID arises from a variety of genetic
      defects. The early intervention of healthy SCID infants without infections
      affords higher survival rate, and newborn screening (NBS) was suggested. T-cell
      receptor (TCR) exicision circles (TRECs) are circular DNA formed from the
      leftover fragment generated from the TCR rearrangement. TRECs can be measured
      from a small aliquot of DNA such as Guthrie card by quantitative PCR. SCID
      patients lack TRECs, and TRECs quantification is useful for NBS for SCID. NBS for
      SCID have been already carried out in most of the Unite States, and the early
      introduction is desired in Japan to save SCID children.

PMID- 28747601
TI  - Leptin and autoimmune disease.
AB  - Leptin is secreted from adipocytes and acts mainly on the hypothalamus causing
      weight loss due to suppression of appetite and increased energy expenditure. On
      the other hand, the leptin receptor is also expressed in hematopoietic cells and
      its action on the immune system has become known, and the significance of leptin
      in autoimmune diseases has gradually become clear. It has been shown that leptin
      acts as an exacerbating factor in many autoimmune diseases and it is suggested
      that inhibition of leptin signal may be a novel therapeutic method for autoimmune
      diseases. In this article, we will outline the significance of leptin in the
      immune system based on the current reports.

PMID- 28747602
TI  - Inflammation amplifier and gateway reflex: The regulation of inflammation by
      neuroimmune interaction.
AB  - Central nervous system (CNS), which is made up of brain and spinal cord, is
      protected from the invasion of harmful agents, such as various pathogens,
      chemical products or immune cells by a special structure "Blood Brain Barrier
      (BBB)". BBB highly preserves the homeostasis of CNS environment. On the other
      hand, there are many diseases in CNS regions which is associated with infection
      or autoimmunity, that means there may exist the "gateway" for pathogens or immune
      cells to attack CNS. Until recently, the molecular mechanism of the gateway
      formation has not been elucidated. Through studies in the multiple sclerosis
      model experimental autoimmune encephalomyelitis, we have clarified the mechanism
      of the gateway formation, and also the locations of gateways which depend on the
      regional neural activation. Further more, we have also discovered a massive
      chemokine-inducing mechanism "inflammation amplifier" via co-activation of NF
      kappaB pathway and STAT3 pathway. It is essential for the development of
      inflammation in various diseases and is a molecular basis of BBB breakdown.

PMID- 28747603
TI  - Autoinflammatory diseases in dermatology: DITRA and CAMPS.
AB  - Deficiency of interleukin thirty-six receptor antagonist (DITRA) and CARD14
      mediated psoriasis (CAMPS) are autoinflammatory diseases in dermatology. The
      causative genes of DITRA and CMAPS have been identified recently. In this paper,
      IL36RN and CARD14, the causative gene for DITRA and CAMPS, respectively were
      explained. In addition, clinical features and therapies for generalized pustular
      psoriasis not associated with psoriasis vulgaris (GPP without PsV), and
      pityriasis rubra pilaris type V (PRP type V) were described. GPP without PsV and
      PRP type V are representative diseases of DITRA and CAMPS, respectively.

PMID- 28747604
TI  - Methotrexate-associated lymphoproliferative disorder.
AB  - Methotrexate-associated lymphproliferative disorder (MTX-LPD) is a rare but
      critical complication developing in patients treated with methotrexate. Now that
      methotrexate is an anchor drug in the management of rheumatoid arthritis and
      become commonly used, MTX-LPD cases have increased. Many things has been unclear
      such as incidence, demographic characters, and risk factors. However, as the
      researches increased, several interesting topics has been demonstrated like
      associations with Epsteiin-Barr virus and with cell-mediated immunity. This
      report reviews newly the latest findings and future challenges on MTX-LPD.

PMID- 28747605
TI  - Omenn Syndrome and DNA recombination defects.
AB  - Mutations in the RAG1/RAG2 genes are associated with a broad spectrum of clinical
      phenotypes, ranging from severe combined immunodeficiency to various autoimmune
      diseases. The diversity of the clinical symptoms is determined not only by the
      residual RAG recombinase enzyme activity as determined by the mutations, but also
      by multiple environmental factors and, in rare cases, by second site mutations
      within the RAG1/RAG2 genes. The residual recombinase activity is responsible for
      the oligoclonal expansion of autoreactive T cells. Omenn syndrome is the result
      of intense Th2 type inflammation involving the skin and multiple other organs
      triggered by these T cells. In this review, the molecular pathology of diseases
      caused by RAG1/RAG2 mutations, in particular Omenn syndrome, will be discussed.
      Furthermore, abnormalities in other molecules involved in V(D)J recombination
      will be discussed in relation to Omenn-like syndrome.

PMID- 28747606
TI  - Effective therapy with infliximab for clinically mild encephalitis/encephalopathy
      with a reversible splenial lesion in an infant with Kawasaki disease.
AB  - Kawasaki disease (KD) is a systemic vasculitis in infants. In KD, encephalopathy
      is rarely (0.1%) associated, however, clinically mild encephalitis/encephalopathy
      with a reversible splenial lesion (MERS) has previously been reported in some
      pediatric patients. Here, we report on a 2-year-old girl who had KD complicated
      with MERS. The patient experienced generalized clonic convulsion and prolonged
      consciousness disturbance with fever for 2 days. Her head MRI showed a high
      signal intensity lesion in the splenium of the corpus callosum in diffusion
      weighted images, and low apparent diffusion coefficient (ADC) values on day 3. An
      electroencephalogram showed high voltage slow waves on the occipital and parietal
      head. On the same day, it was confirmed that the patient showed all the main
      symptoms of KD. Based on these findings, we diagnosed her with MERS-complicated
      KD. Even though she was treated with immunoglobulin (total 4 g/kg) and pulsed
      dose methylprednisolone, her fever and consciousness disturbance continued, and
      blood tests showed that inflammation markers remained high. We then treated the
      patient with infliximab on day 9, and within a few hours of the treatment her
      fever dropped and all symptoms of KD and consciousness disturbance disappeared.
      No recurrence of KD or other complications of KD occurred, and she was discharged
      on day 23. We propose that infliximab is an effective optional treatment for
      immunoglobulin/glucocorticoid-resistant KD with MERS. To clarify this
      possibility, further case accumulation is warranted.

PMID- 28747607
TI  - Safety and effectiveness of certolizumab pegol in patients with rheumatoid
      arthritis: Interim analysis of post-marketing surveillance.
AB  - : Objective: To evaluate the safety and effectiveness of certolizumab pegol (CZP)
      in a real-world setting among Japanese patients with rheumatoid arthritis.
      METHODS: Post-marketing surveillance data from 2,579 patients treated with CZP
      were analyzed. Adverse events (AEs) observed during the 24-week CZP treatment
      period were recorded. Disease activity was evaluated using DAS28-ESR and DAS28
      CRP at baseline, Week 12, Week 24, or at withdrawal. RESULTS: The total period of
      exposure to CZP was 1313.8 patient-years (PY). AEs were reported in 658 (25.5%)
      patients, at an event rate (ER) of 73.68/100 PY. The most frequent serious AEs
      were pneumonia, herpes zoster, and interstitial lung disease, at ER per 100 PY of
      2.06, 1.29, and 1.22, respectively. Mean disease activity scores at baseline, as
      measured by DAS28-ESR and DAS28-CRP, were 4.77 +/- 1.34 and 4.21 +/- 1.27,
      respectively. Mean changes from baseline at the last observation were -1.29 +/-
      1.46 and -1.30 +/- 1.42, respectively. EULAR good or moderate responses were
      achieved in 65% of patients. Longer disease duration, prior biologics use, and
      treatment without MTX co-therapy were associated with EULAR no response.
      CONCLUSION: In this interim analysis, no new safety signals were observed.
      Clinical response to CZP was observed in approximately two thirds of patients.

PMID- 28747608
TI  - IgG4-related disease -Mechanistic insights from both clinical and immunologic
      understanding of this condition.
AB  - IgG4-related disease (IgG4-RD) is a chronic inflammatory disease characterized by
      tumescent lesions with characteristic storiform fibrosis, obliterative phlebitis
      and a marked lymphoplasmacytic infiltrate that includes a large number of IgG4
      positive plasma cells. It's widely accepted that rituximab-mediated B cell
      depletion therapy is effective for this disease. Important mechanistic insights
      correlated with the pathogenesis of IgG4-RD have been gradually disclosed from
      studies of patients treated by B cell depletion. 1) IgG4-RD patients have the
      large clonal expansion of activated plasmablasts and CD4+CTLs, so this disease
      might be antigen-driven. 2) CD4+CTLs are the dominant population in affected
      tissues, on the other hands direct examination of TH1 and TH2 cells in tissues
      reveal that these subsets are sparse. 3) CD4+CTLs into affected lesions secret
      cytotoxic, inflammatory, and pro-fibrotic cytokines, indicating reactivation by
      antigen in tissue sites. 4) The decline in CD4+CTLs number by B cell depletion is
      associated with clinical remission of IgG4-RD patients. 5) CD4+CXCR5+TFH cells
      that express IL-4 are located outside germinal centers and specialized TFH cells
      that expanded dramatically in conditions with polarized class switching to IgG4.
      These results suggested that the disease pathogenesis might be based on
      orchestrating of activated plasmablasts, CD4+CTLs, and TFH cells.

PMID- 28747609
TI  - Increased SUMO-2/3-ylation mediated by SENP3 degradation is protective against
      cadmium-induced caspase 3-dependent cytotoxicity.
AB  - Increased post-translational modification of proteins by SUMO-2/3 is a
      cytoprotective response against cell stress induced by ischaemia and reperfusion.
      However, it is still unclear what other cell stressors trigger protein
      SUMOylation, what mechanisms enhance and maintain the enhanced SUMOylation, and
      if it is a general protective mediator against other cytotoxic stresses. Here, we
      show increased levels of SUMOylation and decreased levels of the SUMO
      deconjugating enzyme SENP3 in PC12 cells treated with the toxic heavy metal
      cadmium. In addition, SENP3 knockdown reduced cadmium-induced caspase 3 cleavage
      and cell death in PC12 cells, while SENP3 overexpression enhanced cell death.
      These results suggest that SENP3 is an important regulator of the cellular
      response to cadmium stress in PC12 cells. Our findings are consistent with
      previous reports of decreased SENP3 and increased SUMOylation in ischaemia, and
      imply that the regulation of SENP3 levels and subsequent changes in SUMOylation
      could be a cytoprotective mechanism against caspase 3-mediated cell death.

PMID- 28747610
TI  - Retraction: Protective effect of SENP3-mediated SUMOylation against cadmium
      toxicity.
AB  - [This retracts the article DOI: 10.2131/jts.42.233.].

PMID- 28747611
TI  - Histone Deacetylase 1 Inhibition Protects Against Hypoxia-Induced Swelling in
      H9c2 Cardiomyocytes Through Regulating Cell Stiffness.
AB  - BACKGROUND: The process of cardiomyocyte swelling involves changes of
      biomechanical properties and profiles of cellular genes. Although many genes have
      been proved to regulate cell edema of cardiomyocyte, the mechanisms involved in
      this event, as well as the biomechanical properties of swelling cell, remain
      unknown.Methods and Results:Whether histone deacetylase 1 (HDAC1) inhibition
      protects against hypoxia-induced H9c2 cardiomyocyte swelling is examined in this
      study. Hypoxia-induced changes in the biomechanical properties and cytoskeletal
      structure that are relevant to cell swelling were also determined. H9c2 cells
      were treated under a chemical hypoxia situation (cobalt chloride) with HDAC1
      inhibition (chemical inhibitor or siRNA) for 5 h, followed by in vitro biological
      and mechanical characterization. The results showed that expression of HDAC1
      instead of HDAC4 was upregulated by chemical hypoxia. HDAC1 inhibition protects
      H9c2 cells against chemical hypoxia-induced hypoxic injury and cell swelling.
      HDAC1 inhibition improved cell viability, decreased lactate dehydrogenase
      leakage, cell apoptosis, malondialdehyde concentration, cell volume, and
      particles on the cell surface, and increased superoxide dismutase activity.
      Moreover, chemical hypoxia induced a decrease of Young's modulus, accompanied by
      alterations in the integrity of acetylated histone and organization of the
      cytoskeletal network. HDAC1 inhibition significantly reversed these processes.
      CONCLUSIONS: Based on the ideal physical model, HDAC1 inhibition protects against
      hypoxia-induced swelling in H9c2 cardiomyocytes through enhancing cell stiffness.
      Overall, HDAC1 is a potential therapeutic target for myocardial edema.

PMID- 28747612
TI  - Effectiveness and Outcome of Pulmonary Arterial Hypertension-Specific Therapy in
      Japanese Patients With Pulmonary Arterial Hypertension.
AB  - BACKGROUND: The trend of the initial treatment strategy for pulmonary arterial
      hypertension (PAH) has changed from monotherapies to upfront combination
      therapies. This study analyzed treatments and outcomes in Japanese patients with
      PAH, using data from the Japan PH Registry (JAPHR), which is the first organized
      multicenter registry for PAH in Japan.Methods and Results:We studied 189
      consecutive patients (108 treatment-naive and 81 background therapy patients)
      with PAH in 8 pulmonary hypertension (PH) centers enrolled from April 2008 to
      March 2013. We performed retrospective survival analyses and analyzed the
      association between upfront combination and hemodynamic improvement, adjusting
      for baseline NYHA classification status. Among the 189 patients, 1-, 2-, and 3
      year survival rates were 97.0% (95% CI: 92.1-98.4), 92.6% (95% CI: 87.0-95.9),
      and 88.2% (95% CI: 81.3-92.7), respectively. In the treatment-naive cohort, 33%
      of the patients received upfront combination therapy. In this cohort, 1-, 2-, and
      3-year survival rates were 97.6% (95% CI: 90.6-99.4), 97.6% (95% CI: 90.6-99.4),
      and 95.7% (95% CI: 86.9-98.6), respectively. Patients on upfront combination
      therapy were 5.27-fold more likely to show hemodynamic improvement at the first
      follow-up compared with monotherapy (95% CI: 2.68-10.36). CONCLUSIONS: According
      to JAPHR data, initial upfront combination therapy is associated with improvement
      in hemodynamic status.

PMID- 28747613
TI  - Increased Carotid Artery Lesion Inflammation Upon Treatment With the CD137
      Agonistic Antibody 2A.
AB  - BACKGROUND: Increased inflammatory activity destabilizes the atherosclerotic
      lesion and may lead to atherothrombosis and symptomatic cardiovascular disease.
      Co-stimulatory molecules, such as CD137, are key regulators of inflammation, and
      CD137 activity regulates inflammation in experimental atherosclerosis. Here, we
      hypothesized that CD137 activation promotes carotid artery inflammation and
      atherothrombosis.Methods and Results:In a model of inducible atherothrombosis
      with surgical ligation of the right carotid artery and a subsequent placement of
      a polyethene cuff, elevated levels of CD137 and CD137 ligand mRNA in
      atherothrombotic vs. non-atherothrombotic murine carotid lesions was observed.
      Mice treated with the CD137 agonistic antibody 2A showed signs of increased
      inflammation in the aorta and a higher proportion of CD8+T cells in spleen and
      blood. In carotid lesions of 2A-treated mice, significantly higher counts of
      CD8+and major histocompatibility (MHC)-class II molecule I-Ab+cells were
      observed. Treatment with the CD137 agonistic antibody 2A did not significantly
      affect the atherothrombosis frequency in 16-week-old mice in this model.
      CONCLUSIONS: Levels of CD137 and CD137 ligand mRNA were higher in advanced
      atherosclerotic disease compared to control vessels, and treatment with the CD137
      agonistic antibody 2A, in a murine model for inducible atherothrombosis promoted
      vascular inflammation, but had no significant effect on atherothrombosis
      frequency at this early disease stage.

PMID- 28747614
TI  - Pyogenic Aortitis - Role of 18F-FDG Positron Emission Tomography/Computed
      Tomography in Aortic Infection Imaging.

PMID- 28747615
TI  - Isolated congenital megacystis with spontaneous resolution: a case report.
AB  - The patient was a male infant with an antenatal diagnosis of huge intraabdominal
      mass. Prenatal ultrasound at 35 weeks gestation revealed a markedly enlarged
      cystic mass in the lower abdomen. After birth at 38 weeks, the infant was allowed
      to void spontaneously and passed meconium. Ultrasonography showed an enlarged
      bladder with wall thickness of 2.9 mm and no hydronephrosis. Voiding
      cystourethrograms showed no evidence of vesicoureteral reflex and posterior
      urethral valve. The post-void residuals were 15 mL at 11 days of life, 5 mL at 1
      month and 0 mL at 5 months. Over 10 years' follow-up, the patient remains
      completely well without any urinary or gastrointestinal symptoms. In sporadic
      isolated congenital megacystis, which is not so rare in fetuses but is quite rare
      in neonates, gastrointestinal symptoms may be masked in the neonatal period;
      however, the present patient has never presented any symptoms.

PMID- 28747616
TI  - Assessment of non-invasive chronic fungal rhinosinusitis by cone beam CT:
      comparison with multidetector CT findings.
AB  - OBJECTIVE: To investigate the accuracy of cone beam CT (CBCT) to diagnose non
      invasive chronic fungal rhinosinusitis. METHODS: Preoperative CT evaluation of
      non-invasive chronic fungal rhinosinusitis was performed by CBCT (3D Accuitomo
      170(r)) and traditional multidetector CT (MDCT) (Aquilion 32(r)) in 13 and 38
      patients with non-invasive chronic fungal maxillary sinusitis, respectively, in
      different facilities. Detection of intrasinus calcification was compared between
      these two groups. RESULTS: Detection of intrasinus calcification in patients with
      non-invasive chronic fungal maxillary sinusitis was higher in the MDCT group
      (84.2%) than the CBCT group (46.2%). CONCLUSION: CBCT is inferior to MDCT in
      detection of intrasinus calcification in patients with non-invasive chronic
      fungal maxillary sinusitis. CBCT is frequently used in the screening of the
      paranasal lesion, but it is not enough to evaluate non-invasive chronic fungal
      maxillary sinusitis alone. STUDY DESIGN: Retrospective study.

PMID- 28747617
TI  - Prolonged infection at the tibial bone tunnel after anterior cruciate ligament
      reconstruction.
AB  - A 24-year-old man with severe atopic dermatitis underwent anterior cruciate
      ligament (ACL) reconstruction of the right knee seven years earlier but developed
      a surgical site infection. The infection did not heal after removal of the metal
      implants, and a fistula eventually developed. This condition was left untreated
      for six years before he was referred to our hospital. Magnetic resonance imaging
      showed fluid in the tibial bone tunnel and extensive bone marrow edema
      surrounding the bone tunnel. Based on these findings, abscess formation within
      the tibial bone tunnel and osteomyelitis spreading to the proximal tibia were
      suspected. During the surgery, a portion of artificial ligament and non
      absorbable suture were observed in the bone tunnel, and the infection healed
      immediately after removal of this complex. When surgical site infection occurs
      after ACL reconstruction, it is important to completely remove all artificial
      materials as early as possible.

PMID- 28747619
TI  - Comparison of Commercially Available Blood Collection Tubes Containing Sodium
      Citrate and Hirudin in Platelet Aggregation Testing.
AB  - BACKGROUND Platelet reactivity assessment is an important tool in both the causal
      determination of bleeding diathesis as well as in the evaluation of the efficacy
      of anti-platelet therapy in patients at risk of thrombosis. Sodium citrate is the
      most widely used anticoagulant for hemostasis investigations. However, some doubt
      exists over the suitability of sodium citrate in platelet function testing.
      Hirudin has been suggested as a superior replacement. Nevertheless, only 1 study
      compared citrated and hirudin treated samples with light transmission
      aggregometry. Therefore, limited evidence exists to conclusively prove the
      supremacy of hirudin over sodium citrate in light transmission aggregometry. The
      aim of our study was to compare citrated and hirudin treated samples, collected
      in commercially available blood collection tubes, using the 5 most common
      agonists, with light transmission aggregometry. MATERIAL AND METHODS Blood was
      obtained from 20 healthy volunteers. Platelet counts were performed on platelet
      rich plasma. Light transmission aggregometry was performed within 4 h of sample
      collection using ADP, collagen, arachidonic acid, epinephrine, and ristocetin as
      agonists. RESULTS Platelet counts for the respective anticoagulants did not
      differ significantly. ADP-induced aggregation was comparable between the samples.
      However, among all the agonists, hirudin-treated platelets had significantly
      weaker aggregatory responses. CONCLUSIONS Commercially available sodium citrate
      should remain the anticoagulant of choice for routine platelet function testing
      in our setting. However, the time limitation associated with the use of sodium
      citrate in platelet function testing remains a concern. Thus, alternative
      anticoagulants should still be explored.

PMID- 28747618
TI  - Comprehensive approach for post-prostatectomy incontinence in the era of robot
      assisted radical prostatectomy.
AB  - Robot-assisted radical prostatectomy (RARP) has enabled steady and stable
      surgical procedures due to both meticulous maneuvers and magnified, clear, 3
      dimensional vision. Therefore, better surgical outcomes have been expected with
      RARP than with other surgical modalities. However, even in the RARP era, post
      prostatectomy incontinence has a relatively high incidence as a bothersome
      complication. To overcome post-prostatectomy incontinence, it goes without saying
      that meticulous surgical procedures and creative surgical procedures, i.e.,
      "Preservation", "Reconstruction", and "Reinforcement" of the anatomical
      structures of the pelvis, are most important. In addition, medication and
      appropriate pad usage might sometimes be helpful for patients with post
      prostatectomy incontinence. However, patients who have 1) BMI > 26 kg/m2, 2)
      prostate volume > 70 mL, 3) eGFR < 60 mL/min, or a 4) Charlson comorbidity index
      > 2 have a tendency to develop post-prostatectomy incontinence despite undergoing
      the same surgical procedures. It is important for patients who have a high risk
      for post-prostatectomy incontinence to be given information about delayed
      recovery of post-prostatectomy incontinence. Thus, not only the surgical
      procedures, but also a comprehensive approach, as mentioned above, are important
      for post-prostatectomy incontinence.

PMID- 28747620
TI  - Chronic Inflammatory Demyelinating Polyneuropathy Variant with Creatine-Kinase
      Elevation and Vanishing Effect of Immunoglobulins.
AB  - BACKGROUND Whether creatine-kinase (CK) is elevated or not in chronic
      inflammatory demyelinating polyneuropathy (CIDP) and its variants is not
      comprehensively investigated. CASE REPORT We report the case of a 47-year-old
      male who developed weakness of the left lower leg and the right index finger at
      age 42 years. At age 44 years, paresthesias and dysesthesias of both lower legs
      and mild right lower leg weakness additionally developed. CK was recurrently
      elevated since age 42 years but paraprotein and anti-myelin-associated
      glycoprotein (MAG)-antibodies were negative. Nerve conduction studies at age 43
      years showed an axonal and demyelinating lesion with conduction blocks.
      Cerebrospinal fluid (CSF) investigations revealed mild pleocytosis and elevated
      protein, which is why CIDP variant was diagnosed. Immunoglobulins were
      administered with success. Because of recurrent relapses, immunoglobulins were
      increased at age 45 years, resulting in stabilization. Currently, the patient is
      infusing immunoglobulins subcutaneously himself. CONCLUSIONS CIDP variants may go
      along with CK elevation, an axonal lesion, pleocytosis, and asymmetry of the
      lesion. A vanishing effect of immunoglobulins over time may be characteristic of
      CIDP variants.

PMID- 28747621
TI  - Evaluation of Biomechanical Changes in Myopia Patients with Unsatisfactory
      Corneas After Femto Second-Laser In Situ Keratomileusis (FS-LASIK) Concurrent
      with Accelerated Corneal Collagen Cross-Linking Using Corvis-ST: Two-Year Follow
      Up Results.
AB  - BACKGROUND Some myopia patients with unsatisfactory corneas consider corneal
      refractive surgery for different reasons. Accelerated corneal collagen
      crosslinking (ACXL) is an effective method to enhance the resistance of the
      cornea. The present investigation was designed to evaluate the changes of
      biomechanical properties in patients with myopia and thin corneas after
      femtosecond-laser in situ keratomileusis (FS-LASIK) concurrent with ACXL.
      MATERIAL AND METHODS A prospective study was designed. A total of 22 eyes of 11
      myopia astigmatism patients with unsatisfactory corneas were enrolled. The
      patients were assigned to femtosecond-laser in situ keratomileusis concurrent
      with accelerated corneal collagen crosslinking (FS-LASIK-ACXL). The follow-up
      duration was 24 months. Manifest refraction, uncorrected (UDVA), and corrected
      distance visual acuity (CDVA), ultra-high-speed camera (Corvis-ST), corneal
      topography, anterior segment OCT (AS-OCT), Pentacam, and endothelial cell density
      (ECD) were examined before and after the operation. The corneal biomechanical and
      refractive data was analyzed using SAS9.3. Data were analyzed through normal
      distribution test and variance of analysis. The difference was considered as
      statistically significant when p<0.05. RESULTS The steep K (Ks) values, flat K
      (Kf) values, average keratometry values (Avek) values, and central corneal
      thickness (CCT) declined significantly after FS-LASIK-ACXL operation. The values
      of first applanation length (A1L), the second applanation length (A2L), the first
      applanation velocity (A1V), the second applanation velocity (A2V), deformation
      amplitude (DA), highest concavity peak distance (PD), and radius of curvature at
      the time of highest concavity (HCR) did not show significant difference after the
      operation. CONCLUSIONS FS-LASIK-ACXL is an effective and safe surgery for
      improving visual acuity for myopic patients with thin corneas, and it does not
      increase the risk of iatrogenic keratectasia.

PMID- 28747622
TI  - Coupled symmetric and asymmetric circuits underlying spatial orientation in fruit
      flies.
AB  - Maintaining spatial orientation when carrying out goal-directed movements
      requires an animal to perform angular path integration. Such functionality has
      been recently demonstrated in the ellipsoid body (EB) of fruit flies, though the
      precise circuitry and underlying mechanisms remain unclear. We analyze recently
      published cellular-level connectomic data and identify the unique characteristics
      of the EB circuitry, which features coupled symmetric and asymmetric rings. By
      constructing a spiking neural circuit model based on the connectome, we reveal
      that the symmetric ring initiates a feedback circuit that sustains persistent
      neural activity to encode information regarding spatial orientation, while the
      asymmetric rings are capable of integrating the angular path when the body
      rotates in the dark. The present model reproduces several key features of EB
      activity and makes experimentally testable predictions, providing new insight
      into how spatial orientation is maintained and tracked at the cellular
      level.Ellipsoid body (EB) neurons in the fruit fly represent the animal heading
      through a bump-like activity dynamics. Here the authors report a connectome
      driven spiking neural circuit model of the EB and the protocerebral bridge (PB)
      that can maintain and update an activity bump related to the spatial orientation.

PMID- 28747623
TI  - Anterior cingulate is a source of valence-specific information about value and
      uncertainty.
AB  - Anterior cingulate cortex (ACC) is thought to control a wide range of reward,
      punishment, and uncertainty-related behaviors. However, how it does so is
      unclear. Here, in a Pavlovian procedure in which monkeys displayed a diverse
      repertoire of reward-related, punishment-related, and uncertainty-related
      behaviors, we show that many ACC-neurons represent expected value and uncertainty
      in a valence-specific manner, signaling value or uncertainty predictions about
      either rewards or punishments. Other ACC-neurons signal prediction information
      about rewards and punishments by displaying excitation to both (rather than
      excitation to one and inhibition to the other). This diversity in valence
      representations may support the role of ACC in many behavioral states that are
      either enhanced by reward and punishment (e.g., vigilance) or specific to either
      reward or punishment (e.g., approach and avoidance). Also, this first
      demonstration of punishment-uncertainty signals in the brain suggests that ACC
      could be a target for the treatment of uncertainty-related disorders of
      mood.Rewards or punishments elicit diverse behavioral responses; however, the
      neural circuits underlying such flexibility are unclear. Here Monosov shows that
      this diversity could be supported by neurons in the anterior cingulate that
      represent expected value and uncertainty in a valence-specific manner.

PMID- 28747624
TI  - Number of infection events per cell during HIV-1 cell-free infection.
AB  - HIV-1 accumulates changes in its genome through both recombination and mutation
      during the course of infection. For recombination to occur, a single cell must be
      infected by two HIV strains. These coinfection events were experimentally
      demonstrated to occur more frequently than would be expected for independent
      infection events and do not follow a random distribution. Previous mathematical
      modeling approaches demonstrated that differences in target cell susceptibility
      can explain the non-randomness, both in the context of direct cell-to-cell
      transmission, and in the context of free virus transmission (Q. Dang et al.,
      Proc. Natl. Acad. Sci. USA 101:632-7, 2004: K. M. Law et al., Cell reports
      15:2711-83, 2016). Here, we build on these notions and provide a more detailed
      and extensive quantitative framework. We developed a novel mathematical model
      explicitly considering the heterogeneity of target cells and analysed datasets of
      cell-free HIV-1 single and double infection experiments in cell culture.
      Particularly, in contrast to the previous studies, we took into account the
      different susceptibility of the target cells as a continuous distribution.
      Interestingly, we showed that the number of infection events per cell during cell
      free HIV-1 infection follows a negative-binomial distribution, and our model
      reproduces these datasets.

PMID- 28747625
TI  - The regulation of Hh/Gli1 signaling cascade involves Gsk3beta- mediated mechanism
      in estrogen-derived endometrial hyperplasia.
AB  - The present study was undertaken to explore the functional involvement of Hh
      signaling and its regulatory mechanism in endometrial hyperplasia. Differential
      expression of Hh signaling molecules i.e., Ihh, Shh, Gli1 or Gsk3beta was
      observed in endometrial hyperplasial (EH) cells as compared to normal endometrial
      cells. Estradiol induced the expression of Hh signaling molecules and attenuated
      the expression of Gsk3beta whereas anti-estrogen (K1) or progestin (MPA)
      suppressed these effects in EH cells. Cyclopamine treatment or Gli1 siRNA
      knockdown suppressed the growth of EH cells and reduced the expression of
      proliferative markers. Estradiol also induced the nuclear translocation of Gli1
      which was suppressed by both MPA and K1 in EH cells. While exploring non
      canonical mechanism, LY-294002 (Gsk3beta activator) caused a decrease in Gli1
      expression indicating the involvement of Gsk3beta in Gli1 regulation. Further,
      Gsk3beta silencing promoted the expression and nuclear translocation of Gli1
      demonstrating that Gsk3beta serves as a negative kinase regulator of Gli1 in EH
      cells. Similar attenuation of Hh signaling molecules was observed in rats with
      uterine hyperplasia undergoing anti-estrogen treatment. The study suggested that
      Hh/Gli1 cascade (canonical pathway) as well as Gsk3beta-Gli1 crosstalk (non
      canonical pathway) play crucial role in estrogen-dependent cell proliferation in
      endometrial hyperplasia.

PMID- 28747626
TI  - Rap2a serves as a potential prognostic indicator of renal cell carcinoma and
      promotes its migration and invasion through up-regulating p-Akt.
AB  - Rap2a, a member of the small GTPase superfamily, belongs to Ras superfamily, and
      its function in cancer progression is still poorly understood. Our previous study
      indicated that the ectopic expression of Rap2a enhanced the migration and
      invasion ability of lung cancer cells. However, its expression and molecular
      mechanism on renal cell carcinoma (RCC) have not been characterized. This study
      explored the clinical significance and biological function of Rap2a in human RCC.
      The clinical relevance of Rap2a in RCC was evaluated by immunohistochemical
      staining using tissue microarray. Our data showed that Rap2a expression was
      dramatically increased in RCC tissues compared with normal renal tissues. The
      ectopic expression of Rap2a enhanced the migration and invasive ability of cancer
      cells. In contrast, downregulation of Rap2a inhibited cell invasion. Rap2a had no
      effect on the proliferation of RCC cell lines. Meanwhile, Rap2a can regulate the
      phosphorylation level of Akt in vitro. In vivo studies also showed that Rap2a
      positively regulated metastasis of renal cancer cells and the expression of p
      Akt. These findings indicate that Rap2a promotes RCC metastasis and may serve as
      a candidate RCC prognostic marker and a potential therapeutic target.

PMID- 28747627
TI  - Metacognitive impairments extend perceptual decision making weaknesses in
      compulsivity.
AB  - Awareness of one's own abilities is of paramount importance in adaptive decision
      making. Psychotherapeutic theories assume such metacognitive insight is impaired
      in compulsivity, though this is supported by scant empirical evidence. In this
      study, we investigate metacognitive abilities in compulsive participants using
      computational models, where these enable a segregation between metacognitive and
      perceptual decision making impairments. We examined twenty low-compulsive and
      twenty high-compulsive participants, recruited from a large population-based
      sample, and matched for other psychiatric and cognitive dimensions. Hierarchical
      computational modelling of the participants' metacognitive abilities on a visual
      global motion detection paradigm revealed that high-compulsive participants had a
      reduced metacognitive ability. This impairment was accompanied by a perceptual
      decision making deficit whereby motion-related evidence was accumulated more
      slowly in high compulsive participants. Our study shows that the compulsivity
      spectrum is associated with a reduced ability to monitor one's own performance,
      over and above any perceptual decision making difficulties.

PMID- 28747628
TI  - The anti-cancer effects of itraconazole in epithelial ovarian cancer.
AB  - We assessed the anti-proliferative activity of itraconazole using an EOC cell
      line (SKOV3ip1) and endothelial cell lines (HUVEC & SVEC4-10). We also examined
      angiogenesis (VEGFR2, p-ERK, p-PLCr1/2), hedgehog (Gli1, Ptch1, SMO), and mTOR
      (pS6K1) signaling pathways to determine the mechanism of action of itraconazole.
      Furthermore, we evaluated the synergistic effects of itraconazole and paclitaxel
      using orthotopic mouse models with established EOC cells (SKOV3ip1 or HeyA8) as
      well as patient-derived xenografts (PDXs). Itraconazole treatment inhibited
      proliferation of endothelial cells in a dose-dependent manner, but had no effect
      on EOC cells. The endothelial cell antiproliferative effect was associated with
      inhibition of hedgehog, and mTOR pathways and angiogenesis. In xenograft models
      of EOC using SKOV3ip1 or HeyA8, mice treated with the combination of itraconazole
      and paclitaxel had significantly decreased tumor weight than the control,
      paclitaxel-alone, or itraconazole-alone groups. Tissue derived from these tumors
      had significantly lower microvessel density than tissue from the other groups as
      well as hedgehog and mTOR pathway inhibition. We confirmed those effects in two
      EOC PDX models. These results suggest that itraconazole selectively inhibits
      endothelial cells rather than cancer cells by targeting multiple pathways
      including hedgehog, and mTOR pathways and angiogenesis.

PMID- 28747629
TI  - Clownfish in hypoxic anemones replenish host O2 at only localised scales.
AB  - The clownfish-anemone association exemplifies a symbiosis where both members
      benefit from nutrient exchange and protection from predators. Clownfish also
      perform aeration-like behaviour in their host anemones at night, but it is not
      yet known whether this is stimulated by the onset of hypoxia, and whether both
      members benefit from O2 replenishment. Oxygen at 3 distances above the sea
      anemone Entacmaea quadricolor (0.2, 1.2 and 2.2 cm) therefore was measured under
      3 light levels (photon flux density = 0, 55 and 110 umol m-2 s-1), with and
      without the anemonefish Amphiprion frenatus. Hypoxia (O2 < 50% air saturation)
      was recorded in the anemone, but only at 0.2 cm away from the anemone surface
      under dark conditions when A. frenatus was absent. This localised layer of
      hypoxia was eliminated by the presence of A. frenatus exhibiting aeration-like
      behaviour. Respirometry revealed that A. frenatus is extremely hypoxia tolerant
      (S crit = 14.3% at 25  degrees C), suggesting that aeration behaviour does not
      provide a major metabolic advantage to clownfish because they do not breathe
      water at 0.2 cm and are not metabolically constrained by O2 at distances >= 1.2
      cm. That the aeration behaviour of A. frenatus facilitates only the metabolism of
      its O2-conforming host reveals a unique aspect of this symbiotic relationship.

PMID- 28747630
TI  - Multiple uprising invasions of Pelophylax water frogs, potentially inducing a new
      hybridogenetic complex.
AB  - The genetic era has revolutionized our perception of biological invasions. Yet,
      it is usually too late to understand their genesis for efficient management.
      Here, we take the rare opportunity to reconstruct the scenario of an uprising
      invasion of the famous water frogs (Pelophylax) in southern France, through a
      fine-scale genetic survey. We identified three different taxa over less than 200
      km2: the autochthonous P. perezi, along with the alien P. ridibundus and P.
      kurtmuelleri, which have suddenly become invasive. As a consequence, the latter
      hybridizes and may now form a novel hybridogenetic complex with P. perezi, which
      could actively promote its replacement. This exceptional situation makes a
      textbook application of genetics to early-detect, monitor and understand the
      onset of biological invasions before they pose a continental-wide threat. It
      further emphasizes the alarming rate of amphibian translocations, both at global
      and local scales, as well as the outstanding invasive potential of Pelophylax
      aliens.

PMID- 28747632
TI  - Ring-like N-fold Models of Abeta42 fibrils.
AB  - When assembling as fibrils Abeta40 peptides can only assume U-shaped
      conformations while Abeta42 can also arrange as S-shaped three-stranded chains.
      We show that this allows Abeta42 peptides to assemble pore-like structures that
      may explain their higher toxicity. For this purpose, we develop a scalable model
      of ring-like assemblies of S-shaped Abeta1-42 chains and study the stability and
      structural properties of these assemblies through atomistic molecular dynamics
      simulations. We find that the proposed arrangements are in size and symmetry
      compatible with experimentally observed Abeta assemblies. We further show that
      the interior pore in our models allows for water leakage as a possible mechanism
      of cell toxicity of Abeta42 amyloids.

PMID- 28747631
TI  - JMJD3 and NF-kappaB-dependent activation of Notch1 gene is required for
      keratinocyte migration during skin wound healing.
AB  - It has been shown that epigenetic regulation plays an important role in skin
      wound healing. We previously found that histone H3K27me3 demethylase JMJD3
      regulates inflammation and cell migration in keratinocyte wound healing. In this
      study, we identified Notch1 as a direct target of JMJD3 and NF-kappaB in wounded
      keratinocytes using in vitro cell and in vivo animal models. We found that Notch1
      is up-regulated in the wound edge and its expression is dependent on JMJD3 and NF
      kappaB in wounded keratinocytes. We also found that Notch1 activates the
      expression of RhoU and PLAU gene, which are critical regulators of cell
      migration. Consistently, depletion or inactivation of Notch1 resulted in
      decreased filopodia formation, increased focal adhesion and actin stress fiber,
      leading to reduced keratinocyte migration and skin wound healing. Thus, our
      findings provide the molecular mechanism involving JMJD3/NF-kappaB-Notch pathway
      in keratinocyte wound healing.

PMID- 28747633
TI  - A room temperature continuous-wave nanolaser using colloidal quantum wells.
AB  - Colloidal semiconductor nanocrystals have emerged as promising active materials
      for solution-processable optoelectronic and light-emitting devices. In
      particular, the development of nanocrystal lasers is currently experiencing rapid
      progress. However, these lasers require large pump powers, and realizing an
      efficient low-power nanocrystal laser has remained a difficult challenge. Here,
      we demonstrate a nanolaser using colloidal nanocrystals that exhibits a threshold
      input power of less than 1 MUW, a very low threshold for any laser using
      colloidal emitters. We use CdSe/CdS core-shell nanoplatelets, which are efficient
      nanocrystal emitters with the electronic structure of quantum wells, coupled to a
      photonic-crystal nanobeam cavity that attains high coupling efficiencies. The
      device achieves stable continuous-wave lasing at room temperature, which is
      essential for many photonic and optoelectronic applications. Our results show
      that colloidal nanocrystals are suitable for compact and efficient optoelectronic
      devices based on versatile and inexpensive solution-processable
      materials.Colloidal nanocrystals are a promising material for easy-to-fabricate
      nanolasers, but suffer from high threshold powers. Here, the authors combine
      colloidal quantum wells with a photonic-crystal cavity into a stable, continuous
      wave room-temperature nanolaser with a threshold below one microwatt.

PMID- 28747634
TI  - Changes of corneal tomography in patients with congenital blepharoptosis.
AB  - The study aimed to evaluate the effect of drooped eyelid on corneal tomography in
      congenital blepharoptosis patients. Sixty-four patients with congenital
      blepharoptosis and 64 age- and sex- matched healthy subjects were included.
      According to the eyelid margin to corneal light reflex distance (MRD), eyes with
      congenital blepharoptosis were categorized as mild, moderate, or severe. The eyes
      were scanned using the rotating Scheimpflug camera. Increased topometric
      parameters were observed in moderate and severe blepharoptosis. Back corneal
      elevations at the thinnest point were significant higher for mild (P = 0.009),
      moderate (P < 0.001), and severe (P < 0.001) congenital blepharoptosis compared
      with controls. Maximum Ambrosio's relational thickness (ART) was decreased in
      eyes with severe blepharoptosis (P < 0.001). Fnal D values were significantly
      higher in moderate (P < 0.001) and severe blepharoptosis (P < 0.001) groups than
      that of controls. There were significant correlations between MRD and most
      corneal tomographic parameters. Our findings indicated there was a trend toward
      subclinical keratoconus-like changes in the corneas of congenital blepharoptosis,
      with the increase of ptosis severity.

PMID- 28747636
TI  - Label-free Electrochemical Detection of ATP Based on Amino-functionalized Metal
      organic Framework.
AB  - A sensitive, selective and recyclable electrochemical sensor is designed for ATP
      detection based on amino-functionalized metal-organic framework. The functional
      MOF as the sensor is constructed by one-step synthesis Ce-MOF and sequentially
      modified on the Au electrode and conjugated with the aptamer of ATP. The presence
      of target ATP leads to the conformational change of aptamer strands and strong
      electrochemical impedance. The electrochemical sensor can detect ATP down to 5.6
      nM with the linear range of 10 nm to 1000 MUM. The present study is the first
      report on the use of MOF as an electrochemical sensor for ATP at nM level. This
      strategy has been successfully applied in detection of ATP in serum of cancer
      patients, which reveals its potential application in clinical diagnosis.

PMID- 28747635
TI  - AIM1 is an actin-binding protein that suppresses cell migration and
      micrometastatic dissemination.
AB  - A defining hallmark of primary and metastatic cancers is the migration and
      invasion of malignant cells. These invasive properties involve altered dynamics
      of the cytoskeleton and one of its major structural components beta-actin. Here
      we identify AIM1 (absent in melanoma 1) as an actin-binding protein that
      suppresses pro-invasive properties in benign prostate epithelium. Depletion of
      AIM1 in prostate epithelial cells increases cytoskeletal remodeling,
      intracellular traction forces, cell migration and invasion, and anchorage
      independent growth. In addition, decreased AIM1 expression results in increased
      metastatic dissemination in vivo. AIM1 strongly associates with the actin
      cytoskeleton in prostate epithelial cells in normal tissues, but not in prostate
      cancers. In addition to a mislocalization of AIM1 from the actin cytoskeleton in
      invasive cancers, advanced prostate cancers often harbor AIM1 deletion and
      reduced expression. These findings implicate AIM1 as a key suppressor of invasive
      phenotypes that becomes dysregulated in primary and metastatic prostate cancer.

PMID- 28747637
TI  - Erratum: Human pressures and ecological status of European rivers.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has not been fixed in the paper.

PMID- 28747638
TI  - PUMA gene delivery to synoviocytes reduces inflammation and degeneration of
      arthritic joints.
AB  - In rheumatoid arthritis (RA), the proliferation of fibroblast-like synoviocytes
      (FLS) is the cause of chronic inflammation in joints and of joint damage.
      Delivery of the pro-apoptotic gene PUMA to FLS via human adenovirus type 5
      (HAdV5) vectors has been tested as a therapeutic approach, but efficiency is
      hampered by low transduction, as FLS do not express HAdV5 receptors on the cell
      surface. Here we show that efficient transduction of PUMA in FLS can be achieved
      by conjugating HAdV5 to a baculovirus, which binds to the cell surface via the
      envelope glycoprotein Gp64. Intra-articular injection in an adjuvant-induced rat
      model of RA induces apoptosis of FLS, leading to significant decrease in joint
      inflammation, joint damage, and bone loss with improvement in joint function and
      mobility. Our results demonstrate the therapeutic potential of PUMA gene therapy
      as a local treatment in various forms of arthritis in which abnormal FLS
      proliferation is implicated.Proliferation of synoviocytes contributes to joint
      damage in rheumatoid arthritis. Here the authors show that targeting of these
      cells by a vector, consisting of a baculovirus conjugated to an adenovirus
      carrying the pro-apoptotic gene PUMA, has therapeutic efficacy in a rat arthritis
      model.

PMID- 28747639
TI  - Molecular profiling of single organelles for quantitative analysis of cellular
      heterogeneity.
AB  - Recent developments in Raman spectroscopy instrumentation and data processing
      algorithms have led to the emergence of Ramanomics - an independent discipline
      with unprecedented capabilities to map the distribution of distinct molecular
      groups in live cells. Here, we introduce a method for probing the absolute
      concentrations of proteins, RNA and lipids in single organelles of live cultured
      cells by biomolecular component analysis using microRaman data. We found
      significant cell-to-cell variations in the molecular profiles of organelles, thus
      providing a physiologically relevant set of markers of cellular heterogeneity. At
      the same cell the molecular profiles of different organelles can strongly
      correlate, reflecting tight coordination of their functions. This correlation was
      significant in WI-38 diploid fibroblasts and weak in HeLa cells, indicating
      profound differences in the regulation of biochemical processes in these cell
      lines.

PMID- 28747640
TI  - Structural and physical determinants of the proboscis-sucking pump complex in the
      evolution of fluid-feeding insects.
AB  - Fluid-feeding insects have evolved a unique strategy to distribute the labor
      between a liquid-acquisition device (proboscis) and a sucking pump. We
      theoretically examined physical constraints associated with coupling of the
      proboscis and sucking pump into a united functional organ. Classification of
      fluid feeders with respect to the mechanism of energy dissipation is given by
      using only two dimensionless parameters that depend on the length and diameter of
      the proboscis food canal, maximum expansion of the sucking pump chamber, and
      chamber size. Five species of Lepidoptera - White-headed prominent moth
      (Symmerista albifrons), White-dotted prominent moth (Nadata gibosa), Monarch
      butterfly (Danaus plexippus), Carolina sphinx moth (Manduca sexta), and Death's
      head sphinx moth (Acherontia atropos) - were used to illustrate this
      classification. The results provide a rationale for categorizing fluid-feeding
      insects into two groups, depending on whether muscular energy is spent on moving
      fluid through the proboscis or through the pump. These findings are relevant to
      understanding energetic costs of evolutionary elaboration and reduction of the
      mouthparts and insect diversification through development of new habits by fluid
      feeding insects in general and by Lepidoptera in particular.

PMID- 28747641
TI  - Evolution of Phase, Microstructure and ZrC Lattice Parameter in Solid-solution
      treated W-ZrC Composite.
AB  - Zirconium carbide (ZrC) reinforced tungsten (W) composite was hot-pressed at 2200
      degrees C for 1 h in vacuum, which was subsequently heat treated in the
      temperature range of 2200 to 2500  degrees C for 1.5 or 2 h. The relative ratios
      of ZrC phase were 21.0, 23.3 and 25.9 mol.% for the mixture of starting powders,
      composites sintered for 1 h and solid-solution treated at 2500  degrees C for 1.5
      h, respectively. The solid solubility of W in ZrC increased with the increment in
      heat-treating temperature and time to a maximum value of 18.9 mol.% at 2500 
      degrees C for 1.5 h. The lattice parameter of cubic ZrC phase diminished from
      0.4682 nm in the starting powder to 0.4642 nm in the solid-solution composite
      treated at 2500  degrees C for 1.5 h. This work demonstrated that the
      relationship between the solid solubility of W in ZrC and the lattice parameter
      of ZrC is linear, with a slope of -1.93 * 10-4 nm/at.%. Overall, more W atoms
      diffused into ZrC lattice after heat treatment, meanwhile, the previous
      precipitated nano-sized W dissolved in the supersaturated (Zr,W)C solid-solution,
      as detected by SEM and TEM.

PMID- 28747642
TI  - A preliminary study of 18F-FES PET/CT in predicting metastatic breast cancer in
      patients receiving docetaxel or fulvestrant with docetaxel.
AB  - The present explorative study was initiated to evaluate the clinical value of 18F
      FES PET/CT in monitoring the change of estrogen receptor (ER) expression and
      potential predictive value in metastatic breast cancer patients. Twenty-two
      pathology-confirmed breast cancer patients were prospectively enrolled and
      randomly divided into two groups (T: docetaxel, n = 14 and TF: docetaxel +
      fulvestrant, n = 8). The percentage of patients without disease progression after
      12 months (PFS > 12 months) was 62.5% in group TF compared with 21.4% in group T
      (P = 0.08). According to 18F-FES PET/CT scans, the SUVmax (maximum standard
      uptake value) of all the metastatic lesions decreased in group TF after 2 cycles
      of treatment (6 weeks +/- 3 days). However, 6 of 9 patients in group T had at
      least one lesion with higher post-treatment SUVmax. There was a significant
      difference in the reduction of ER expression between these two groups (P =
      0.028). In group TF, the patients with PFS > 12 months had significantly greater
      SUVmax changes of 18F-FES than those with PFS < 12 months (PFS > 12 months: 91.0
      +/- 12.0% versus PFS < 12 months: 20.7 +/- 16.2%; t = -4.64, P = 0.01). Our
      preliminary study showed that 18F-FES PET/CT, as a noninvasive method to monitor
      ER expression, could be utilized to predict prognosis based on changes in SUVmax.

PMID- 28747643
TI  - Generation of ribosome imprinted polymers for sensitive detection of
      translational responses.
AB  - Whilst the profiling of the transcriptome and proteome even of single-cells
      becomes feasible, the analysis of the translatome, which refers to all messenger
      RNAs (mRNAs) engaged with ribosomes for protein synthesis, is still an elaborate
      procedure requiring millions of cells. Herein, we report the generation and use
      of "smart materials", namely molecularly imprinted polymers (MIPs) to facilitate
      the isolation of ribosomes and translated mRNAs from merely 1,000 cells. In
      particular, we show that a hydrogel-based ribosome imprinted polymer could
      recover ribosomes and associated mRNAs from human, simian and mice cellular
      extracts, but did not selectively enrich yeast ribosomes, thereby demonstrating
      selectivity. Furthermore, ribosome imprinted polymers enabled the sensitive
      measurement of an mRNA translational regulatory event, requiring 1,000-fold less
      cells than current methodologies. These results provide first evidence for the
      suitability of MIPs to selectively recover ribonucleoprotein complexes such as
      ribosomes, founding a novel means for sensitive detection of gene regulation.

PMID- 28747644
TI  - Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism
      for early neutrophil response to Mycobacterium marinum.
AB  - The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain
      poorly understood. In this study we utilise biotagging, a novel genome-wide
      profiling approach based on cell type-specific in vivo biotinylation in zebrafish
      to analyse the initial response of neutrophils to Mycobacterium marinum, a close
      genetic relative of M. tuberculosis used to model tuberculosis. Differential
      expression analysis following nuclear RNA-seq of neutrophil active transcriptomes
      reveals a significant upregulation in both damage-sensing and effector components
      of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and
      il1beta. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic
      processing of il1beta, results in increased bacterial burden and less
      infiltration of macrophages to sites of mycobacterial infection, thus impairing
      granuloma development. We also show that a number of immediate early response
      genes (IEGs) are responsible for orchestrating the initial neutrophil response to
      mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key
      transcriptional regulator controlling il1beta transcription.

PMID- 28747645
TI  - Quantum Parametric Mode Sorting: Beating the Time-Frequency Filtering.
AB  - Selective detection of signal over noise is essential to measurement and signal
      processing. Time-frequency filtering has been the standard approach for the
      optimal detection of non-stationary signals. However, there is a fundamental
      tradeoff between the signal detection efficiency and the amount of undesirable
      noise detected simultaneously, which restricts its uses under weak signal yet
      strong noise conditions. Here, we demonstrate quantum parametric mode sorting
      based on nonlinear optics at the edge of phase matching to improve the tradeoff.
      By tailoring the nonlinear process in a commercial lithium-niobate waveguide
      through optical arbitrary waveform generation, we demonstrate highly selective
      detection of picosecond signals overlapping temporally and spectrally but in
      orthogonal time-frequency modes as well as against broadband noise, with
      performance well exceeding the theoretical limit of the optimized time-frequency
      filtering. We also verify that our device does not introduce any significant
      quantum noise to the detected signal and demonstrate faithful detection of pico
      second single photons. Together, these results point to unexplored opportunities
      in measurement and signal processing under challenging conditions, such as photon
      starving quantum applications.

PMID- 28747646
TI  - Metabolic Biomarkers for Prognostic Prediction of Pre-diabetes: results from a
      longitudinal cohort study.
AB  - To investigate the metabolic biomarkers of predicting the transition from pre
      diabetes (pre-DM) to normal glucose regulation (NGR) and diabetes (DM) in a
      longitudinal cohort study. 108 participants with pre-DM were followed up for ten
      years and divided into 3 groups according to different glycemic outcomes. 20
      participants progressed to DM, 20 regressed to NGR, and 68 remained at pre-DM.
      Alterations in plasma metabolites in these groups were evaluated by untargeted
      ultra-performance liquid chromatography-quadrupole time-of-flight mass
      spectrometry (UPLC-QTOF-MS). Twenty three metabolites related to
      glycerophospholipid metabolism, oxidation and antioxidation were associated with
      the process from pre-DM to NGR, while twenty two metabolites related to amino
      acid metabolism, glycerophospholipid metabolism and mitochondrial beta-oxidation
      played important roles in the progression to DM. Results from stepwise logistic
      regression analysis showed that five biomarkers (20-Hydroxy-leukotriene E4,
      Lysopc(20:4), 5-methoxytryptamine, Endomorphin-1, Lysopc(20:3)) were good
      prediction for the restoration to NGR, and five biomarkers (Iso-valeraldehyde,
      linoleic acid, Lysopc(18:1), 2-Pyrroloylglycine, Dityrosine) for the development
      of DM. The findings suggest that the combination of these potential metabolites
      may be used for the prognosis of pre-DM. Targeting the pathways that involved in
      these prognostic biomarkers would be beneficial for the regression to NGR and the
      early prevention of DM among pre-DM.

PMID- 28747647
TI  - Delivery of intracavernosal therapies using needle-free injection devices.
AB  - ED affects a significant proportion of males worldwide. With an ever-aging
      population the prevalence of ED is predicted to double in the next decade. Oral
      PDE-5 inhibitors are the first-line treatment for ED and have revolutionised its
      management. These agents are however ineffective in some men. Intracavernosal
      injection (ICI) of vasoactive agents is an effective second-line therapy for ED.
      Despite proven efficacy, needle phobia and anxiety with self-needling limit the
      use of intracavernosal (IC) therapies. Needle-free injection (NFI) devices allow
      delivery of parenteral therapies through the skin, without a needle. Although
      these devices have been available for decades, early studies investigating their
      use for ICI showed inferiority compared to standard needle-tip syringe delivery.
      Advances in engineering of these systems have lead to functional improvements of
      many aspects of fluid delivery. Our research demonstrates that modern NFI devices
      are better equipped to deliver ICI, and, in the cadaver models examined, achieved
      successful IC delivery. These findings support the potential feasibility of NFI
      devices to deliver ICI, and may broaden the utility of these devices to patients
      who refuse or discontinue IC therapy because of needle phobia or other issues
      with standard needle-tip syringes.

PMID- 28747648
TI  - Resting-state brain connectivity changes in obese women after Roux-en-Y gastric
      bypass surgery: A longitudinal study.
AB  - Bariatric surgery is an effective method to rapidly induce weight loss in
      severely obese people, however its impact on brain functional connectivity after
      longer periods of follow-up is yet to be assessed. We investigated changes in
      connectivity in 16 severely obese women one month before, one month after and one
      year after Roux-en-Y gastric bypass surgery (RYGB). 12 lean controls were also
      enrolled. Resting-state fMRI was acquired for all participants following an
      overnight fast and after a 260 kcal load. Connectivity between regions involved
      in food-related saliency attribution and reward-driven eating behavior was
      stronger in presurgery patients compared to controls, but progressively weakened
      after follow-up. At one year, changes in networks related to cognitive control
      over eating and bodily perception also occurred. Connectivity between regions
      involved in emotional control and social cognition had a temporary reduction
      early after treatment but had increased again after one year of follow-up.
      Furthermore, we could predict the BMI loss by presurgery connectivity in areas
      linked to emotional control and social interaction. RYGBP seems to reshape brain
      functional connectivity, early affecting cognitive control over eating, and these
      changes could be an important part of the therapeutic effect of bariatric
      surgery.

PMID- 28747649
TI  - Magnetocapacitance in La0.7Sr0.3MnO3/Pb(Zr0.2Ti0.8)O3/La0.7Sr0.3MnO3 multiferroic
      heterostructures.
AB  - Measurements of the magnetocapacitance effect in epitaxial
      La0.7Sr0.3MnO3/Pb(Zr0.2Ti0.8)O3/La0.7Sr0.3MnO3 heterostructures have been
      performed using a quasi-static method. Through capacitance-voltage measurements
      carried out under variable magnetic field it has been found that the magneto
      capacitance depends on the orientation of the ferroelectric polarization. The
      value of magneto-capacitance can be as high as 1% in the voltage range near the
      ferroelectric coercive field. This has been attributed to a variation of the
      apparent built-in voltage of the PZT-LSMO Schottky barriers on applied magnetic
      field.

PMID- 28747650
TI  - Removal of back-reflection noise at ultrathin imaging probes by the single-core
      illumination and wide-field detection.
AB  - Thin waveguides such as graded-index lenses and fiber bundles are often used as
      imaging probes for high-resolution endomicroscopes. However, strong back
      reflection from the end surfaces of the probes makes it difficult for them to
      resolve weak contrast objects, especially in the reflectance-mode imaging. Here
      we propose a method to spatially isolate illumination pathways from detection
      channels, and demonstrate wide-field reflectance imaging free from back
      reflection noise. In the image fiber bundle, we send illumination light through
      individual core fibers and detect signals from target objects through the other
      fibers. The transmission matrix of the fiber bundle is measured and used to
      reconstruct a pixelation-free image. We demonstrated that the proposed imaging
      method improved 3.2 times on the signal to noise ratio produced by the
      conventional illumination-detection scheme.

PMID- 28747651
TI  - Critical Behavior and Macroscopic Phase Diagram of the Monoaxial Chiral
      Helimagnet Cr1/3NbS2.
AB  - Cr1/3NbS2 is a unique example of a hexagonal chiral helimagnet with high
      crystalline anisotropy, and has generated growing interest for a possible
      magnetic field control of the incommensurate spin spiral. Here, we construct a
      comprehensive phase diagram based on detailed magnetization measurements of a
      high quality single crystal of Cr1/3NbS2 over three magnetic field regions. An
      analysis of the critical properties in the forced ferromagnetic region yields 3D
      Heisenberg exponents beta = 0.3460 +/- 0.040, gamma = 1.344 +/- 0.002, and T C =
      130.78 K +/- 0.044, which are consistent with the localized nature the of Cr3+
      moments and suggest short-range ferromagnetic interactions. We exploit the
      temperature and magnetic field dependence of magnetic entropy change (DeltaS M)
      to accurately map the nonlinear crossover to the chiral soliton lattice regime
      from the chiral helimagnetic phase. Our observations in the low field region are
      consistent with the existence of chiral ordering in a temperature range above the
      Curie temperature, T C < T < T*, where a first-order transition has been
      previously predicted. An analysis of the universal behavior of DeltaS M(T,H)
      experimentally demonstrates for the first time the first-order nature of the
      onset of chiral ordering.

PMID- 28747652
TI  - Non-aqueous selective synthesis of orthosilicic acid and its oligomers.
AB  - Orthosilicic acid (Si(OH)4) and its small condensation compounds are among the
      most important silicon compounds but have never been isolated, due to their
      instability. These compounds would be highly useful building blocks for advanced
      materials if they became available at high purity. Here we show a simple
      procedure to selectively synthesize orthosilicic acid and its dimer, cyclic
      trimer and tetramer in organic solvents. Isolation of orthosilicic acid, the
      dimer and the cyclic tetramer as hydrogen-bonded crystals with tetrabutylammonium
      halides and the cyclic trimer as solvent-containing crystals is also described.
      The solid-state structures of these compounds are unambiguously clarified by
      single crystal X-ray and neutron diffraction studies. The usefulness of
      orthosilicic acid and its oligomers prepared by the new procedure is demonstrated
      by the synthesis of functionalized oligosiloxanes.Orthosilicic acid is essential
      to many natural and synthetic materials but notoriously difficult to isolate,
      limiting its use in materials synthesis. Here, the authors successfully
      synthesize and stabilize orthosilicic acid and its oligomers, making available a
      new family of building blocks for silicon oxide-based materials.

PMID- 28747653
TI  - Amino group in Leptothrix sheath skeleton is responsible for direct deposition of
      Fe(III) minerals onto the sheaths.
AB  - Leptothrix species produce microtubular organic-inorganic materials that encase
      the bacterial cells. The skeleton of an immature sheath, consisting of organic
      exopolymer fibrils of bacterial origin, is formed first, then the sheath becomes
      encrusted with inorganic material. Functional carboxyl groups of polysaccharides
      in these fibrils are considered to attract and bind metal cations, including
      Fe(III) and Fe(III)-mineral phases onto the fibrils, but the detailed mechanism
      remains elusive. Here we show that NH2 of the amino-sugar-enriched exopolymer
      fibrils is involved in interactions with abiotically generated Fe(III) minerals.
      NH2-specific staining of L. cholodnii OUMS1 detected a terminal NH2 on its sheath
      skeleton. Masking NH2 with specific reagents abrogated deposition of Fe(III)
      minerals onto fibrils. Fe(III) minerals were adsorbed on chitosan and NH2-coated
      polystyrene beads but not on cellulose and beads coated with an acetamide group.
      X-ray photoelectron spectroscopy at the N1s edge revealed that the terminal NH2
      of OUMS1 sheaths, chitosan and NH2-coated beads binds to Fe(III)-mineral phases,
      indicating interaction between the Fe(III) minerals and terminal NH2. Thus, the
      terminal NH2 in the exopolymer fibrils seems critical for Fe encrustation of
      Leptothrix sheaths. These insights should inform artificial synthesis of highly
      reactive NH2-rich polymers for use as absorbents, catalysts and so on.

PMID- 28747654
TI  - Analytical investigation of nonreciprocal response in 1D nonlinear photonic
      crystals.
AB  - The nonreciprocal response of the SHG process in 1D periodical nonlinear photonic
      crystals with a defect embedded has been theoretically studied by solving the
      nonlinear coupled equations. The nonreciprocal response has been deduced
      analytically with the solution of non-reciprocity parameters obtained. The result
      shows that as the non-reciprocity approaches 100%, the crystal length and the
      input power needed increase at a logarithmic rate. Any target nonreciprocal
      response can be reached in this structure by adjusting the structure parameters.

PMID- 28747655
TI  - Strategies to Mitigate Variability in Engineering Human Nasal Cartilage.
AB  - Skin cancer and its associated treitments can have devastating consequences for
      survivors; this is particularly true when cancer occurs on the nose. Recent work
      has applied cell-based tissue engineering (TE) strategies to develop nasal
      cartilage constructs for reconstruction of the nose. In this study, we have
      generated human nasal cartilage on a clinically approved collagen scaffold to
      investigate the donor-to-donor variability of TE cartilage and evaluated
      strategies to mitigate it. We also evaluated the gene expression of the family of
      fibroblast growth factor receptors (FGFR1-4) and their association with tissue
      quality. FGFR 1 was significantly positively correlated with GAG/DNA; a measure
      of chondrogenic capacity. We implemented two strategies: hypoxic culture and co
      culture with mesenchymal stromal cells (MSCs) to increase tissue quality. Total
      glycosaminoglycan (GAG) content varied significantly between donors initially,
      with >10-fold difference between the best and worst donor tissue. Our co-culture
      strategy was able to increase TE construct quality from poor quality donor tissue
      while supressing hypertrophy relative to MSCs alone. However, no differences were
      observed with the use of hypoxic culture. Tissues generated using co-culture with
      MSCs became vascularized and calcified in vivo, demonstrating a non-stable
      cartilage phenotype in co-culture and MSCs cartilage constructs.

PMID- 28747656
TI  - Modification of the contact surfaces for improving the puncture resistance of
      laminar structures.
AB  - Uncovering energy absorption and surface effects of various penetrating
      velocities on laminar structures is essential for designing protective
      structures. In this study, both quasi-static and dynamic penetration tests were
      systematical conducted on the front surfaces of metal sheets coated with a
      graphene oxide (GO) solution and other media. The addition of a GO fluid film to
      the front impact surface aided in increasing the penetration strength, improving
      the failure extension and dissipating additional energy under a wide-range of
      indentation velocity, from 3.33 * 10-5 m/s to 4.42 m/s. The coated -surfaces
      improved the specific energy dissipation by approximately 15~40% relative to the
      dry-contact configuration for both single-layer and double-layer configurations,
      and specific energy dissipations of double-layer configurations were 20~30%
      higher than those of the single-layer configurations. This treatment provides a
      facile strategy in changing the contact state for improving the failure load and
      dissipate additional energy.

PMID- 28747657
TI  - Comparisons of three different methods for defining sarcopenia: An aspect of
      cardiometabolic risk.
AB  - Appraisal of muscle mass is important when considering the serious consequences
      of sarcopenia in an aging society. However, the associations between sarcopenia
      and its clinical outcomes might vary according to the method applied in its
      diagnosis. We compared the relationships between cardiometabolic risk parameters
      and sarcopenia defined according to three different diagnostic methods using dual
      energy X-ray absorptiometry (DXA) and computed tomography (CT). Appendicular
      skeletal muscle mass (ASM) adjusted by height squared and BMI (ASM/height2 and
      ASM/BMI) measured using DXA and thigh muscle cross-sectional area (tmCSA)
      adjusted by weight (tmCSA/weight) measured using CT were used as indices of
      muscle mass. Sarcopenia was defined as two standard deviations below either the
      mean ASM/height2, ASM/BMI, or tmCSA/weight of a young reference group. ASM/BMI
      and tmCSA/weight showed a negative relationship with several components of
      metabolic syndrome and HOMA-IR, whereas ASM/height2 was positively associated
      with theses cardiometabolic risk factors. Logistic regression analyses
      demonstrated that ASM/BMI-defined sarcopenia was significantly associated with
      increased HOMA-IR (P = 0.01) and prevalence of visceral obesity (P = 0.03) and
      metabolic syndrome (P = 0.025), while ASM/height2- and tmCSA/weight-defined
      sarcopenia were not. ASM/BMI-defined sarcopenia exhibits a closer relationship
      with cardiometabolic risk factors than does ASM/height2- or tmCSA/weight-defined
      sarcopenia.

PMID- 28747658
TI  - A single amino acid substitution confers B-cell clonogenic activity to the HIV-1
      matrix protein p17.
AB  - Recent data highlight the presence, in HIV-1-seropositive patients with lymphoma,
      of p17 variants (vp17s) endowed with B-cell clonogenicity, suggesting a role of
      vp17s in lymphomagenesis. We investigated the mechanisms responsible for the
      functional disparity on B cells between a wild-type p17 (refp17) and a vp17 named
      S75X. Here, we show that a single Arginine (R) to Glycine (G) mutation at
      position 76 in the refp17 backbone (p17R76G), as in the S75X variant, is per se
      sufficient to confer a B-cell clonogenic potential to the viral protein and
      modulate, through activation of the PTEN/PI3K/Akt signaling pathway, different
      molecules involved in apoptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ,
      Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8,
      CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha). Moreover, the only R to G
      mutation at position 76 was found to strongly impact on protein folding and
      oligomerization by altering the hydrogen bond network. This generates a
      conformational shift in the p17 R76G mutant which enables a functional
      epitope(s), masked in refp17, to elicit B-cell growth-promoting signals after its
      interaction with a still unknown receptor(s). Our findings offer new
      opportunities to understand the molecular mechanisms accounting for the B-cell
      growth-promoting activity of vp17s.

PMID- 28747659
TI  - Porcine familial adenomatous polyposis model enables systematic analysis of early
      events in adenoma progression.
AB  - We compared gene expression in low and high-grade intraepithelial dysplastic
      polyps from pigs carrying an APC 1311 truncating mutation orthologous to human
      APC 1309 , analysing whole samples and microdissected dysplastic epithelium. Gene
      set enrichment analysis revealed differential expression of gene sets similar to
      human normal mucosa versus T1 stage polyps. Transcriptome analysis of whole
      samples revealed many differentially-expressed genes reflecting immune
      infiltration. Analysis of microdissected dysplastic epithelium was markedly
      different and showed increased expression in high-grade intraepithelial neoplasia
      of several genes known to be involved in human CRC; and revealed possible new
      roles for GBP6 and PLXND1. The pig model thus facilitates analysis of CRC
      pathogenesis.

PMID- 28747660
TI  - 4-dimensional functional profiling in the convulsant-treated larval zebrafish
      brain.
AB  - Functional neuroimaging, using genetically-encoded Ca2+ sensors in larval
      zebrafish, offers a powerful combination of high spatiotemporal resolution and
      higher vertebrate relevance for quantitative neuropharmacological profiling. Here
      we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with
      light sheet microscopy and a novel image processing pipeline, for the 4D
      profiling of chemoconvulsant action in multiple brain regions. In untreated
      larvae, regions associated with autonomic functionality, sensory processing and
      stress-responsiveness, consistently exhibited elevated spontaneous activity. The
      application of drugs targeting different convulsant mechanisms (4-Aminopyridine,
      Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct
      spatiotemporal patterns of activity. These activity patterns showed some
      interesting parallels with what is known of the distribution of their respective
      molecular targets, but crucially also revealed system-wide neural circuit
      responses to stimulation or suppression. Drug concentration-response curves of
      neural activity were identified in a number of anatomically-defined zebrafish
      brain regions, and in vivo larval electrophysiology, also conducted in 4dpf
      larvae, provided additional measures of neural activity. Our quantification of
      network-wide chemoconvulsant drug activity in the whole zebrafish brain
      illustrates the power of this approach for neuropharmacological profiling in
      applications ranging from accelerating studies of drug safety and efficacy, to
      identifying pharmacologically-altered networks in zebrafish models of human
      neurological disorders.

PMID- 28747661
TI  - Into the Dynamics of a Supramolecular Polymer at Submolecular Resolution.
AB  - To rationally design supramolecular polymers capable of self-healing or
      reconfiguring their structure in a dynamically controlled way, it is imperative
      to gain access into the intrinsic dynamics of the supramolecular polymer (dynamic
      exchange of monomers) while maintaining a high-resolution description of the
      monomer structure. But this is prohibitively difficult at experimental level.
      Here we show atomistic, coarse-grained modelling combined with advanced
      simulation approaches to characterize the molecular mechanisms and relative
      kinetics of monomer exchange in structural variants of a synthetic supramolecular
      polymer in different conditions. We can capture differences in supramolecular
      dynamics consistent with the experimental observations, revealing that monomer
      exchange in and out the fibres originates from the defects present in their
      supramolecular structure. At the same time, the submolecular resolution of this
      approach offers a molecular-level insight into the dynamics of these bioinspired
      materials, and a flexible tool to obtain structure-dynamics relationships for a
      variety of polymeric assemblies.Accessing the dynamics of soft self-assembled
      materials at high resolution is very difficult. Here the authors show atomistic
      and coarse-grained modelling combined with enhanced sampling to characterize the
      molecular mechanisms and kinetics of monomer exchange in synthetic supramolecular
      polymers.

PMID- 28747662
TI  - Inference of neuronal functional circuitry with spike-triggered non-negative
      matrix factorization.
AB  - Neurons in sensory systems often pool inputs over arrays of presynaptic cells,
      giving rise to functional subunits inside a neuron's receptive field. The
      organization of these subunits provides a signature of the neuron's presynaptic
      functional connectivity and determines how the neuron integrates sensory stimuli.
      Here we introduce the method of spike-triggered non-negative matrix factorization
      for detecting the layout of subunits within a neuron's receptive field. The
      method only requires the neuron's spiking responses under finely structured
      sensory stimulation and is therefore applicable to large populations of
      simultaneously recorded neurons. Applied to recordings from ganglion cells in the
      salamander retina, the method retrieves the receptive fields of presynaptic
      bipolar cells, as verified by simultaneous bipolar and ganglion cell recordings.
      The identified subunit layouts allow improved predictions of ganglion cell
      responses to natural stimuli and reveal shared bipolar cell input into distinct
      types of ganglion cells.How a neuron integrates sensory information requires
      knowledge about its functional presynaptic connections. Here the authors report a
      new method using non-negative matrix factorization to identify the layout of
      presynaptic bipolar cell inputs onto retinal ganglion cells and predict their
      responses to natural stimuli.

PMID- 28747663
TI  - Four dimensional material movies: High speed phase-contrast tomography by
      backprojection along dynamically curved paths.
AB  - We present an approach towards four dimensional (4d) movies of materials, showing
      dynamic processes within the entire 3d structure. The method is based on
      tomographic reconstruction on dynamically curved paths using a motion model
      estimated by optical flow techniques, considerably reducing the typical motion
      artefacts of dynamic tomography. At the same time we exploit x-ray phase contrast
      based on free propagation to enhance the signal from micron scale structure
      recorded with illumination times down to a millisecond (ms). The concept is
      demonstrated by observing the burning process of a match stick in 4d, using high
      speed synchrotron phase contrast x-ray tomography recordings. The resulting
      movies reveal the structural changes of the wood cells during the combustion.

PMID- 28747664
TI  - Mutations targeting the coagulation pathway are enriched in brain metastases.
AB  - Brain metastases (BMs) are the most common malignancy of the central nervous
      system. Recently it has been demonstrated that plasminogen activator inhibitor
      serpins promote brain metastatic colonization, suggesting that mutations in
      serpins or other members of the coagulation cascade can provide critical
      advantages during BM formation. We performed whole-exome sequencing on matched
      samples of breast cancer and BMs and found mutations in the coagulation pathway
      genes in 5 out of 10 BM samples. We then investigated the mutational status of 33
      genes belonging to the coagulation cascade in a panel of 29 BMs and we identified
      56 Single Nucleotide Variants (SNVs). The frequency of gene mutations of the
      pathway was significantly higher in BMs than in primary tumours, and SERPINI1 was
      the most frequently mutated gene in BMs. These findings provide direction in the
      development of new strategies for the treatment of BMs.

PMID- 28747665
TI  - Associations of statin use with motor performance and myalgia may be modified by
      25-hydroxyvitamin D: findings from a British birth cohort.
AB  - The objective was to examine whether: (1) statin use was associated with muscle
      related outcomes at age 60-64, (2) these associations were modified by 25
      hydroxyvitamin D (25(OH)D) status and explained by inflammation, body-size or
      lifestyle in a British birth cohort. Markers of myalgia (intrusive body pain) and
      myopathy (self-reported and performance-based measures) were examined in 734 men
      and 822 women (MRC National Survey of Health and Development). Statin use was
      associated with intrusive body pain, difficulty climbing stairs and slower chair
      rise speed. Some associations were modified by 25(OH)D e.g. the association with
      intrusive body pain was evident in the insufficient (13-20 ng/l) and deficient
      (<13 ng/l) 25(OH)D status groups (OR = 2.6,95% CI 1.7-1.1; OR = 1.8,95% CI 1.2
      2.8, respectively) but not in those with status >20 ng/l (OR = 0.8,95% CI 0.5
      1.4) (p = 0.003 for interaction). Associations were maintained in fully adjusted
      models of intrusive body pain and difficulty climbing stairs, but for chair rise
      speed they were fully accounted for by inflammation, body-size and lifestyle. In
      a nationally representative British population in early old age, statin use was
      associated with lower limb muscle-related outcomes, and some were only apparent
      in those with 25(OH)D status below 20 ng/l. Given 25(OH)D is modifiable in
      clinical practice, future studies should consider the links between 25(OH)D
      status and muscle related outcomes.

PMID- 28747666
TI  - Comparative Analysis of Four Buckwheat Species Based on Morphology and Complete
      Chloroplast Genome Sequences.
AB  - Buckwheat is a nutritional and economically crop belonging to Polygonaceae,
      Fagopyrum. To better understand the mutation patterns and evolution trend in the
      chloroplast (cp) genome of buckwheat, and found sufficient number of variable
      regions to explore the phylogenetic relationships of this genus, two complete cp
      genomes of buckwheat including Fagopyrum dibotrys (F. dibotrys) and Fagopyrum
      luojishanense (F. luojishanense) were sequenced, and other two Fagopyrum cp
      genomes were used for comparative analysis. After morphological analysis, the
      main difference among these buckwheat were height, leaf shape, seeds and flower
      type. F. luojishanense was distinguishable from the cultivated species easily.
      Although the F. dibotrys and two cultivated species has some similarity, they
      different in habit and component contents. The cp genome of F. dibotrys was
      159,320 bp while the F. luojishanense was 159,265 bp. 48 and 61 SSRs were found
      in F. dibotrys and F. luojishanense respectively. Meanwhile, 10 highly variable
      regions among these buckwheat species were located precisely. The phylogenetic
      relationships among four Fagopyrum species based on complete cp genomes was
      showed. The results suggested that F. dibotrys is more closely related to
      Fagopyrum tataricum. These data provided valuable genetic information for
      Fagopyrum species identification, taxonomy, phylogenetic study and molecular
      breeding.

PMID- 28747667
TI  - RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to
      inflammation mediated by the selective jumonji H3K27 demethylase inhibitor.
AB  - Persistent microglial activation is associated with the production and secretion
      of various pro-inflammatory genes, cytokines and chemokines, which may initiate
      or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27
      (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exert
      immunosuppressive activities in macrophages. However, a genome-wide search for
      GSK-J4 molecular targets has not been undertaken in microglia. To study the
      immuno-modulatory effects of GSK-J4 at the transcriptomic level, triplicate RNA
      sequencing and quantitative real-time PCR analyses were performed with resting,
      GSK-J4-, LPS- and LPS + GSK-J4-challenged primary microglial (PM) and BV-2
      microglial cells. Among the annotated genes, the transcriptional sequencing of
      microglia that were treated with GSK-J4 revealed a selective effect on LPS
      induced gene expression, in which the induction of cytokines/chemokines,
      interferon-stimulated genes, and prominent transcription factors TFs, as well as
      previously unidentified genes that are important in inflammation was suppressed.
      Furthermore, we showed that GSK-J4 controls are important inflammatory gene
      targets by modulating STAT1, IRF7, and H3K27me3 levels at their promoter sites.
      These unprecedented results demonstrate that the histone demethylase inhibitor
      GSK-J4 could have therapeutic applications for neuroinflammatory diseases.

PMID- 28747668
TI  - Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic
      Separation of Leukocytes Directly from Whole Blood.
AB  - The separation of leukocytes from whole blood is a prerequisite for many
      biological assays. Traditional methods require significant sample volumes and are
      often undesirable because they expose leukocytes to harsh physical or chemical
      treatment. Existing microfluidic approaches can work with smaller volumes, but
      lack selectivity. In particular, the selectivity of microfluidic systems based on
      microfiltration is limited by fouling due to clogging. Here, we developed a
      method to separate leukocytes from whole blood using the microfluidic ratchet
      mechanism, which filters the blood sample using a matrix of micrometer-scale
      tapered constrictions. Deforming single cells through such constrictions requires
      directionally asymmetrical forces, which enables oscillatory flow to create a
      ratcheting transport that depends on cell size and deformability. Simultaneously,
      oscillatory flow continuously agitates the cells to limit the contact time with
      the filter microstructure to prevent adsorption and clogging. We show this device
      is capable of isolating leukocytes from whole blood with 100% purity (i.e. no
      contaminant erythrocytes) and <2% leukocytes loss. We further demonstrate the
      potential to phenotypically sort leukocytes to enrich for granulocytes and
      lymphocytes subpopulations. Together, this process provides a sensitive method to
      isolate and sort leukocytes directly from whole blood based on their biophysical
      properties.

PMID- 28747669
TI  - Compressive sampling based on frequency saliency for remote sensing imaging.
AB  - In saliency-based compressive sampling (CS) for remote sensing image signals, the
      saliency information of images is used to allocate more sensing resources to
      salient regions than to non-salient regions. However, the pulsed cosine transform
      method can generate large errors in the calculation of saliency information
      because it uses only the signs of the coefficients of the discrete cosine
      transform for low-resolution images. In addition, the reconstructed images can
      exhibit blocking effects because blocks are used as the processing units in CS.
      In this work, we propose a post-transform frequency saliency CS method that
      utilizes transformed post-wavelet coefficients to calculate the frequency
      saliency information of images in the post-wavelet domain. Specifically, the
      wavelet coefficients are treated as the pixels of a block-wise megapixel sensor.
      Experiments indicate that the proposed method yields better-quality images and
      outperforms conventional saliency-based methods in three aspects: peak signal-to
      noise ratio, mean structural similarity index, and visual information fidelity.

PMID- 28747671
TI  - Erratum: Perfluorooctanesulfonate (PFOS)-induced Sertoli cell injury through a
      disruption of F-actin and microtubule organization is mediated by Akt1/2.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 28747670
TI  - PKC-? is dispensable for OX40L-induced TCR-independent Treg proliferation but
      contributes by enabling IL-2 production from effector T-cells.
AB  - We have previously shown that OX40L/OX40 interaction is critical for TCR
      independent selective proliferation of Foxp3+ Tregs, but not Foxp3- effector T
      cells (Teff), when CD4+ T-cells are co-cultured with GM-CSF derived bone marrow
      dendritic cells (G-BMDCs). Events downstream of OX40L/OX40 interaction in Tregs
      responsible for this novel mechanism are not understood. Earlier, OX40L/OX40
      interaction has been shown to stimulate CD4+ T-cells through the formation of a
      signalosome involving TRAF2/PKC-? leading to NF-kB activation. In this study,
      using CD4+ T-cells from WT and OX40-/- mice we first established that OX40
      mediated activation of NF-kB was critical for this Treg proliferation. Although
      CD4+ T-cells from PKC-?-/- mice were also defective in G-BMDC induced Treg
      proliferation ex vivo, this defect could be readily corrected by adding exogenous
      IL-2 to the co-cultures. Furthermore, by treating WT, OX40-/-, and PKC-?-/- mice
      with soluble OX40L we established that OX40L/OX40 interaction was required and
      sufficient to induce Treg proliferation in vivo independent of PKC-? status.
      Although PKC-? is dispensable for TCR-independent Treg proliferation per se, it
      is essential for optimum IL-2 production by Teff cells. Finally, our findings
      suggest that OX40L binding to OX40 likely results in recruitment of TRAF1 for
      downstream signalling.

PMID- 28747672
TI  - Fast switching cholesteric liquid crystal optical beam deflector with
      polarization independence.
AB  - Optical beam deflectors based on the combination of cholesteric liquid crystals
      and polymer micro gratings are reported. Dual frequency cholesteric liquid
      crystal (DFCh-LC) is adopted to accelerate the switching from the homeotropic
      state back to the planar state. Polarization independent beam steering components
      are realized whose transmission versus the polarizing angle only varies 4.4% and
      2.6% for the planar state and the homeotropic state, respectively. A response
      time of 451 ms is achieved for DFCh-LC-grating beam deflectors, which is fast
      compared to other nematic LC beam steerers with similar LC thickness.

PMID- 28747673
TI  - Engineered isopeptide bond stabilized fibrin inspired nanoscale peptide based
      sealants for efficient blood clotting.
AB  - Designing biologically inspired nanoscale molecular assembly with desired
      functionality is a challenging endeavour. Here we report the designing of fibrin
      inspired nanostructured peptide based sealants which facilitate remarkably fast
      entrapping of blood corpuscles (~28 seconds) in contrast to fibrin (~56 seconds).
      Our engineered sealants are stabilized by lysine-aspartate ionic interactions and
      also by Nepsilon(gamma-glutamyl) lysine isopeptide bond mediated covalent
      interaction. Each sealant is formed by two peptides having complementary charges
      to promote lysine-aspartate ionic interactions and designed isopeptide bond
      mediated interactions. Computational analysis reveals the isopeptide bond
      mediated energetically favourable peptide assemblies in sealants 1-3. Our
      designed sealants 2 and 3 mimic fibrin-mediated clot formation mechanism in
      presence of transglutaminase enzyme and blood corpuscles. These fibrin-inspired
      peptides assemble to form sealants having superior hemostatic activities than
      fibrin. Designed sealants feature mechanical properties, biocompatibility,
      biodegradability and high adhesive strength. Such nature-inspired robust sealants
      might be potentially translated into clinics for facilitating efficient blood
      clotting to handle traumatic coagulopathy and impaired blood clotting.

PMID- 28747674
TI  - Increased Prevalence of Severe Fever with Thrombocytopenia Syndrome in Eastern
      China Clustered with Multiple Genotypes and Reasserted Virus during 2010-2015.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne viral
      disease with high mortality. Since January 2010, we have conducted an
      epidemiological surveillance and etiological study of SFTS in Jiangsu and Anhui
      provinces. From January 2010 through December 2015, a total of 286 SFTS cases
      were confirmed in Jiangsu and Anhui provinces with a case fatality rate of 16.1%.
      The majority of confirmed SFTS cases were distributed in the border area of
      Jiangsu and Anhui provinces. Our findings suggest that the SFTS prevalence rate
      rose since 2010 and reached its highest in 2015. Phylogenetic analysis
      demonstrated that the majority of the SFTSV strains (83.6%) from Jiangsu and
      Anhui provinces belonged to genotypes A and D. Notably, we identified three
      strains of SFTSV clustered into the genotype E. This is the first report of the
      genotype E SFTSV strains in mainland of China. A reassortment between genotype A
      and D was found in the central region of the endemic areas, where three SFTSV
      genotypes (A, C and D) were co-circulating.

PMID- 28747675
TI  - High-energy mid-infrared sub-cycle pulse synthesis from a parametric amplifier.
AB  - High-energy phase-stable sub-cycle mid-infrared pulses can provide unique
      opportunities to explore phase-sensitive strong-field light-matter interactions
      in atoms, molecules and solids. At the mid-infrared wavelength, the Keldysh
      parameter could be much smaller than unity even at relatively modest laser
      intensities, enabling the study of the strong-field sub-cycle electron dynamics
      in solids without damage. Here we report a high-energy sub-cycle pulse
      synthesiser based on a mid-infrared optical parametric amplifier and its
      application to high-harmonic generation in solids. The signal and idler combined
      spectrum spans from 2.5 to 9.0 um. We coherently synthesise the passively carrier
      envelope phase-stable signal and idler pulses to generate 33 MUJ, 0.88-cycle,
      multi-gigawatt pulses centred at ~4.2 MUm, which is further energy scalable. The
      mid-infrared sub-cycle pulse is used for driving high-harmonic generation in thin
      silicon samples, producing harmonics up to ~19th order with a continuous spectral
      coverage due to the isolated emission by the sub-cycle driver.Stable sub-cycle
      pulses in the mid-infrared region allow damage-free investigation of electron
      dynamics in solids. Here, the authors develop a suitable source to this end which
      is based on an optical parametric amplifier.

PMID- 28747676
TI  - Uremia does not affect neointima formation in mice.
AB  - Atherosclerotic cardiovascular disease is a major complication of chronic kidney
      disease (CKD). CKD leads to uremia, which modulates the phenotype of aortic
      smooth muscle cells (SMCs). Phenotypic modulation of SMCs plays a key role in
      accelerating atherosclerosis. We investigated the hypothesis that uremia
      potentiates neointima formation in response to vascular injury in mice. Carotid
      wire injury was performed on C57BL/6 wt and apolipoprotein E knockout (Apoe -/-)
      mice two weeks after induction of uremia by 5/6 nephrectomy. Wire injury led to
      neointima formation and downregulation of genes encoding classical SMC markers
      (i.e., myocardin, alpha-smooth muscle actin, SM22-alpha, and smooth muscle myosin
      heavy chain) in both wt and Apoe -/- mice. Contrary to our expectations, uremia
      did not potentiate neointima formation, nor did it affect intimal lesion
      composition as judged from magnetic resonance imaging and histological analyses.
      Also, there was no effect of uremia on SMC marker gene expression in the injured
      carotid arteries, suggesting that there may be different effects of uremia on
      SMCs in different vascular beds. In conclusion, uremia does not accelerate
      neointima formation in response to wire injury of the carotid artery in mice.

PMID- 28747677
TI  - Comprehensive analysis of human protein N-termini enables assessment of various
      protein forms.
AB  - Various forms of protein (proteoforms) are generated by genetic variations,
      alternative splicing, alternative translation initiation, co- or post
      translational modification and proteolysis. Different proteoforms are in part
      discovered by characterizing their N-terminal sequences. Here, we introduce an N
      terminal-peptide-enrichment method, Nrich. Filter-aided negative selection formed
      the basis for the use of two N-blocking reagents and two endoproteases in this
      method. We identified 6,525 acetylated (or partially acetylated) and 6,570 free
      protein N-termini arising from 5,727 proteins in HEK293T human cells. The protein
      N-termini included translation initiation sites annotated in the UniProtKB
      database, putative alternative translational initiation sites, and N-terminal
      sites exposed after signal/transit/pro-peptide removal or unknown processing,
      revealing various proteoforms in cells. In addition, 46 novel protein N-termini
      were identified in 5' untranslated region (UTR) sequence with pseudo start
      codons. Our data showing the observation of N-terminal sequences of mature
      proteins constitutes a useful resource that may provide information for a better
      understanding of various proteoforms in cells.

PMID- 28747678
TI  - The liver-enriched lnc-LFAR1 promotes liver fibrosis by activating TGFbeta and
      Notch pathways.
AB  - Long noncoding RNAs (lncRNAs) play important roles in various biological
      processes such as proliferation, cell death and differentiation. Here, we show
      that a liver-enriched lncRNA, named liver fibrosis-associated lncRNA1 (lnc
      LFAR1), promotes liver fibrosis. We demonstrate that lnc-LFAR1 silencing impairs
      hepatic stellate cells (HSCs) activation, reduces TGFbeta-induced hepatocytes
      apoptosis in vitro and attenuates both CCl4- and bile duct ligation-induced liver
      fibrosis in mice. Lnc-LFAR1 promotes the binding of Smad2/3 to TGFbetaR1 and its
      phosphorylation in the cytoplasm. Lnc-LFAR1 binds directly to Smad2/3 and
      promotes transcription of TGFbeta, Smad2, Smad3, Notch2 and Notch3 which, in
      turn, results in TGFbeta and Notch pathway activation. We show that the
      TGFbeta1/Smad2/3/lnc-LFAR1 pathway provides a positive feedback loop to increase
      Smad2/3 response and a novel link connecting TGFbeta with Notch pathway. Our work
      identifies a liver-enriched lncRNA that regulates liver fibrogenesis and suggests
      it as a potential target for fibrosis treatment.Activated hepatic stellate cells
      are the principal contributors to liver fibrosis by secreting a variety of pro
      fibrogenic cytokines . Here Zhang et al. demonstrate that a liver-enriched
      lncRNA, lnc-LFAR1, promotes liver fibrosis and HSC activation by activating
      TGFbeta and Notch signaling.

PMID- 28747679
TI  - Gambling-like behavior in pigeons: 'jackpot' signals promote maladaptive risky
      choice.
AB  - Individuals often face choices that have uncertain outcomes and have important
      consequences. As a model of this environment, laboratory experiments often offer
      a choice between an uncertain, large reward that varies in its probability of
      delivery against a certain but smaller reward as a measure of an individual's
      risk aversion. An important factor generally lacking from these procedures are
      gambling related cues that may moderate risk preferences. The present experiment
      offered pigeons choices between unreliable and certain rewards but, for the
      Signaled group on winning choices, presented a 'jackpot' signal prior to reward
      delivery. The Unsignaled group received an ambiguous stimulus not informative of
      choice outcomes. For the Signaled group, presenting win signals effectively
      blocked value discounting for the large, uncertain outcome as the probability of
      a loss increased, whereas the Unsignaled group showed regular preference changes
      similar to previous research lacking gambling related cues. These maladaptive
      choices were further shown to be unaffected by more salient loss signals and
      resistant to response cost increases. The results suggest an important role of an
      individual's sensitivity to outcome-correlated cues in influencing risky choices
      that may moderate gambling behaviors in humans, particularly in casino and other
      gambling-specific environments.

PMID- 28747680
TI  - Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum,
      Eph receptor therapeutic antagonist.
AB  - Eph receptors have emerged as targets for therapy in both neoplastic and non
      neoplastic disease, however, particularly in non-neoplastic diseases, redundancy
      of function limits the effectiveness of targeting individual Eph proteins. We
      have shown previously that a soluble fusion protein, where the EphA4 ectodomain
      was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and
      demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist. However, a
      very short in vivo half-life effectively limited its therapeutic development. We
      report a unique glycoengineering approach to enhance the half-life of EphA4 Fc.
      Progressive deletion of three demonstrated N-linked sites in EphA4 progressively
      increased in vivo half-life such that the triple mutant protein showed
      dramatically improved pharmacokinetic characteristics. Importantly, protein
      stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was
      fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin
      antagonist for use in both acute and chronic diseases.

PMID- 28747681
TI  - Template-free synthesis of polystyrene monoliths for the removal of oil-in-water
      emulsion.
AB  - Oil-in-water emulsions are harmful to both humankind and environment. Frequent
      oil spill disasters make it urgent to develop low cost and high-efficiency
      materials for the treatment of oil-in-water emulsions. In this study, we report
      the facile template-free synthesis of macroporous polystyrene (PS) monolith from
      PS solution using a thermally-induced phase separation (TIPS) technique. The
      fabricated monolith showed high hydrophobicity, superoleophilicity, and
      macroporous structure. Moreover, the monolith exhibited high removal efficiency
      toward different oil-in-water emulsions. The monolith can be fabricated from
      cheap and commonly-used plastic. Thus, we anticipate that this research will
      contribute to both the recycling of PS and the treatment of oil spill accidents.

PMID- 28747682
TI  - Quantum optical measurements with undetected photons through vacuum field
      indistinguishability.
AB  - Quantum spectroscopy and imaging with undetected idler photons have been
      demonstrated by measuring one-photon interference between the corresponding
      entangled signal fields from two spontaneous parametric down conversion (SPDC)
      crystals. In this Report, we present a new quantum optical measurement scheme
      utilizing three SPDC crystals in a cascading arrangement; here, neither the
      detection of the idler photons which interact with materials of interest nor
      their conjugate signal photons which do not interact with the sample is required.
      The coherence of signal beams in a single photon W-type path-entangled state is
      induced and modulated by indistinguishabilities of the idler beams and crucially
      the quantum vacuum fields. As a result, the optical properties of materials or
      objects interacting with the idler beam from the first SPDC crystal can be
      measured by detecting second-order interference between the signal beams
      generated by the other two SPDC crystals further down the set-up. This
      gedankenexperiment illustrates the fundamental importance of vacuum fields in
      generating an optical tripartite entangled state and thus its crucial role in
      quantum optical measurements.

PMID- 28747683
TI  - Failure in Cognitive Suppression of Negative Affect in Adolescents with
      Generalized Anxiety Disorder.
AB  - Hyperactivity of limbic (e.g., amygdalar) responses to negative stimuli has been
      implicated in the pathophysiology of generalized anxiety disorder (GAD). Evidence
      has also suggested that even a simple cognitive task involving emotionally
      salient stimuli can modulate limbic and prefrontal neural activation. However,
      whether neural modulation of emotional stimulus processing in a cognitive task is
      defective in adolescents with GAD has not yet been investigated. In this study,
      20 adolescents with GAD and 14 comparable healthy controls underwent event
      related functional magnetic resonance imaging (fMRI) coupled with an emotional
      valence evaluation task. During the evaluation of negative versus neutral
      stimuli, we found significant activation of the right inferior frontal gyrus
      (IFG) in healthy controls, while the bilateral amygdala was activated in GAD
      patients. Between-group analyses showed dramatically reduced task-activation of
      the right IFG in GAD patients, and the magnitude of IFG activity negatively
      correlated with symptom severity. Psychophysiological interaction analysis
      further revealed significantly decreased functional interaction between right IFG
      and anterior cingulate cortex and ventromedial prefrontal cortex in GAD patients
      compared with healthy controls. Taken together, our findings show failure to
      suppress negative affect by recruiting a cognitive distraction in adolescents
      with GAD, providing new insights into the pathophysiology of GAD.

PMID- 28747684
TI  - Generation and validation of novel adeno-associated viral vectors for the
      analysis of Ca2+ homeostasis in motor neurons.
AB  - A finely tuned Ca2+ homeostasis in restricted cell domains is of fundamental
      importance for neurons, where transient Ca2+ oscillations direct the proper
      coordination of electro-chemical signals and overall neuronal metabolism. Once
      such a precise regulation is unbalanced, however, neuronal functions and
      viability are severely compromised. Accordingly, disturbed Ca2+ metabolism has
      often been claimed as a major contributor to different neurodegenerative
      disorders, such as amyotrophic lateral sclerosis that is characterised by
      selective motor neuron (MN) damage. This notion highlights the need for probes
      for the specific and precise analysis of local Ca2+ dynamics in MNs. Here, we
      generated and functionally validated adeno-associated viral vectors for the
      expression of gene-encoded fluorescent Ca2+ indicators targeted to different cell
      domains, under the transcriptional control of a MN-specific promoter. We
      demonstrated that the probes are specifically expressed, and allow reliable local
      Ca2+ measurements, in MNs from murine primary spinal cord cultures, and can also
      be expressed in spinal cord MNs in vivo, upon systemic administration to newborn
      mice. Preliminary analyses using these novel vectors have shown larger cytosolic
      Ca2+ responses following stimulation of AMPA receptors in the cytosol of primary
      cultured MNs from a murine genetic model of ALS compared to the healthy
      counterpart.

PMID- 28747685
TI  - Fast modal decomposition for optical fibers using digital holography.
AB  - Eigenmode decomposition of the light field at the output end of optical fibers
      can provide fundamental insights into the nature of electromagnetic-wave
      propagation through the fibers. Here we present a fast and complete modal
      decomposition technique for step-index optical fibers. The proposed technique
      employs digital holography to measure the light field at the output end of the
      multimode optical fiber, and utilizes the modal orthonormal property of the basis
      modes to calculate the modal coefficients of each mode. Optical experiments were
      carried out to demonstrate the proposed decomposition technique, showing that
      this approach is fast, accurate and cost-effective.

PMID- 28747686
TI  - Memory and Perception-based Facial Image Reconstruction.
AB  - Visual memory for faces has been extensively researched, especially regarding the
      main factors that influence face memorability. However, what we remember exactly
      about a face, namely, the pictorial content of visual memory, remains largely
      unclear. The current work aims to elucidate this issue by reconstructing face
      images from both perceptual and memory-based behavioural data. Specifically, our
      work builds upon and further validates the hypothesis that visual memory and
      perception share a common representational basis underlying facial identity
      recognition. To this end, we derived facial features directly from perceptual
      data and then used such features for image reconstruction separately from
      perception and memory data. Successful levels of reconstruction were achieved in
      both cases for newly-learned faces as well as for familiar faces retrieved from
      long-term memory. Theoretically, this work provides insights into the content of
      memory-based representations while, practically, it may open the path to novel
      applications, such as computer-based 'sketch artists'.

PMID- 28747687
TI  - Protected surface state in stepped Fe (0 18 1).
AB  - Carbon (C) surface segregation from bulk stabilizes the Fe(0 18 1) vicinal
      surface by forming a c(3[Formula: see text] * [Formula: see text] reconstruction
      with C zig-zag chains oriented at 45 degrees  with respect to the iron surface
      steps. The iron surface electronic states as measured by high resolution ARPES at
      normal emission with polarized synchrotron radiation split in two peaks that
      follow distinct energy dispersion curves. One peak follows the dispersion of the
      carbon superstructure and is photoexcited only when the polarization vector is
      parallel to the steps, the second peak disperses similarly to the pristine Fe(0 0
      1) surface. Such surface electronic structure is robust as it persists even after
      coating with an Ag overlayer. The robustness of this surface electronic structure
      and its similarity with that of the clean Fe(0 0 1) surface make this system of
      interest for magnetic and spintronic properties such as magneto tunnel junctions
      based on Fe/MgO interface.

PMID- 28747688
TI  - Spleen contributes to restraint stress induced changes in blood leukocytes
      distribution.
AB  - Psychological stress has great impacts on the immune system, particularly the
      leukocytes distribution. Although the impacts of acute stress on blood leukocytes
      distribution are well studied, however, it remains unclear how chronic stress
      affects leukocytes distribution in peripheral circulation. Furthermore, there is
      no report about the role of spleen in the blood leukocytes distribution induced
      by stress. Here we show that spleen contributes to the alteration of restraint
      stress induced blood leukocytes distribution. Our data confirmed that restraint
      stress induced anxiety-like behavior in mice. Furthermore, we found that
      restraint stress decreased the CD4/CD8 ratio and elevated the percentages of
      natural killer cells, monocytes and polymorphonuclear myeloid-derived suppressor
      cell. We demonstrated that activation of hypothalamic-pituitary-adrenal axis
      (HPA) and sympathetic nervous system (SNS) contributes to restraint stress
      induced alteration of blood leukocyte distribution. Interestingly, we found that
      splenectomy could reverse the change of CD4/CD8 ratio induced by restraint
      stress. Together, our findings suggest that activation of HPA axis and SNS was
      responsible for the blood leukocyte subsets changes induced by restraint stress.
      Spleen, at least in part, contributed to the alteration in peripheral circulation
      induced by restraint stress.

PMID- 28747689
TI  - Niches and Interspecific Associations of Dominant Populations in Three Changed
      Stages of Natural Secondary Forests on Loess Plateau, P.R. China.
AB  - Ecological niches remain central to explaining community structure, and niche
      based studies have helped us to better understand species interactions,
      distributions, coexistence and associated mechanisms. Quercus wutaishansea
      populations on Loess Plateau are currently expanding their dominance in natural
      secondary forest types. In the present paper, we focused on the dynamic changes
      of niches and interspecific association among different changed stages. The
      overall interspecies association of the three communities exhibited positive
      association for Variance Ratio (VR) >1; the value of chi2 significance test
      further revealed that the overall association had reached the level of
      significant association. Among the total of 45 species pairs composed of 10
      dominant species, in the Pinus tabulaeformis forest, the ratio of positive and
      negative associations was below 1, which 19 pairs showing positive association,
      25 pairs showing negative association, and 1 pair showing no association; in
      contrast, in another forests, the ratios of positive and negative associations
      were above 1. The timing and consequences of these associations may illuminate
      how interaction mechanisms such as competition and alleopathy, structure changes.
      Then differences of species features in niches and associations should receive
      greater attention when planning forest management and developing restoration
      strategies.

PMID- 28747690
TI  - Postmortem genetic analysis of sudden unexpected death in infancy: neonatal
      genetic screening may enable the prevention of sudden infant death.
AB  - Tandem mass screening has recently been started in Japan, but genetic screening
      has yet to be widely performed in neonates and many unexpected deaths are still
      being reported. We previously reported two cases of sudden infant death that may
      have been prevented had newborn screening been performed. In this study, we
      retrospectively reviewed 71 cases of sudden infant death for 66 arrhythmia- and
      63 metabolic disease-related genes to identify how many cases of sudden infant
      death may have been prevented had mass screening been performed. Next-generation
      sequencing revealed that six cases had arrhythmia-related gene variants and five
      cases had metabolic disease-related gene variants. Had genetic screening been
      performed in addition to biochemical and physiological screening during the
      neonatal period to identify those at risk of arrhythmia or metabolic disease,
      these infants could have been diagnosed and treated, preventing their deaths. As
      such, screening of newborns may prevent sudden infant death.

PMID- 28747691
TI  - The absence that makes the difference: choroidal abnormalities in Legius
      syndrome.
AB  - Neurofibromatosis type 1 (NF1) is an hereditary disorder characterized by
      abnormal proliferation of multiple tissues of neural crest origin, and presents
      mainly with multiple cafe-au-lait macules, axillary freckling and neurofibromas.
      Choroidal involvement in NF1 patients has been studied, thanks to the development
      of non-invasive tools such as infrared monochromatic light during fundus
      examination, which showed bright patchy lesions consistent with choroidal
      nodules. Choroidal abnormalities identified with near-infrared reflectance have
      reported with a frequency of up to 100% in NF1, and have been recently been
      proposed as a novel diagnostic criterion for NF1. Legius syndrome can be
      clinically indistinguishable from NF1 and results in a small percentage of
      individuals being misdiagnosed. We investigated the presence of choroidal
      abnormalities in Legius syndrome to determine their specificity to NF1 and their
      potential usefulness as a novel diagnostic criterion for NF1. We examined the
      fundus of 16 eyes by confocal scanning laser ophthalmoscopy with infrared
      monochromatic light in eight patients with molecularly confirmed Legius syndrome.
      No abnormalities were observed, confirming the diagnostic value of choroidal
      abnormalities for the diagnosis of NF1.

PMID- 28747692
TI  - New criteria for the molecular identification of cereal grains associated with
      archaeological artefacts.
AB  - The domestication and transmission of cereals is one of the most fundamental
      components of early farming, but direct evidence of their use in early culinary
      practices and economies has remained frustratingly elusive. Using analysis of a
      well-preserved Early Bronze Age wooden container from Switzerland, we propose
      novel criteria for the identification of cereal residues. Using gas
      chromatography mass spectrometry (GC-MS), we identified compounds typically
      associated with plant products, including a series of phenolic lipids
      (alkylresorcinols) found only at appreciable concentration in wheat and rye bran.
      The value of these lipids as cereal grain biomarkers were independently
      corroborated by the presence of macrobotanical remains embedded in the deposit,
      and wheat and rye endosperm peptides extracted from residue. These findings
      demonstrate the utility of a lipid-based biomarker for wheat and rye bran and
      offer a methodological template for future investigations of wider range of
      archaeological contexts. Alkylresorcinols provide a new tool for residue analysis
      which can help explore the spread and exploitation of cereal grains, a
      fundamental component of the advent and spread of farming.

PMID- 28747693
TI  - Expression profile of intestinal stem cell markers in colitis-associated
      carcinogenesis.
AB  - The intestinal epithelium has two distinct two stem cell populations, namely,
      crypt base columnar (CBC) cells and +4 cells. Several specific markers have been
      identified for each stem cell population. In this study, we examined the
      expression profiles of these markers in colitis-associated carcinogenesis (CAC)
      to investigate whether they can be used as biomarkers for the early detection of
      dysplasia. The expression of intestinal stem cell (ISC) markers was measured by
      real-time polymerase chain reaction during CAC that was induced by azoxymethane
      and dextran sodium sulfate treatment. CBC stem cell markers increased
      continuously with tumor development, whereas a +4 cell expression profile was not
      present. CBC stem cell population was suppressed in the acute colitis and then
      expanded to repopulate the crypts during the regeneration period. Notably, RNA in
      situ hybridization revealed that all dysplasia and cancer samples showed
      increased expression of CBC stem cell markers in more than one-third of the tumor
      height, whereas regenerative glands had CBC stem cell markers confined to the
      lower one-third of the crypt. These results suggest that CBC stem cell markers
      could be a useful tool for the early detection of colitis-induced tumors.

PMID- 28747694
TI  - Decreasing parental task specialization promotes conditional cooperation.
AB  - How much to invest in parental care and by who remain puzzling questions fomented
      by a sexual conflict between parents. Negotiation that facilitates coordinated
      parental behaviour may be key to ease this costly conflict. However,
      understanding cooperation requires that the temporal and sex-specific variation
      in parental care, as well as its multivariate nature is considered. Using a
      biparental bird species and repeated sampling of behavioural activities
      throughout a major part of reproduction, we show a clear division of tasks
      between males and females in provisioning, brooding and foraging. Such
      behavioural specializations fade with increasing nestling age, which stimulates
      the degree of alternated feeding visits, as a recently promoted form of
      conditional cooperation. However, such cooperation is thought to benefit
      offspring development, which is not supported by our data. Thus, from a proximate
      point of view, conditional cooperation via alternation critically depends on the
      division of parental tasks, while the ultimate benefits have yet to be shown.

PMID- 28747695
TI  - Compounds that enhance the tailing activity of Moloney murine leukemia virus
      reverse transcriptase.
AB  - In a previous study, we showed that MMLV-RT has a strong terminal transferase
      activity, and that the C-, G-, and T-tailing activities are enhanced by dGMP,
      dCMP, and dAMP, respectively. In this study, to achieve faster reaction and
      higher tailing efficiency, we screened other compounds for the ability to enhance
      the tailing activities of MMLV-RT, and determined the corresponding optimal
      concentrations. The C-, G-, and T-tailing activities were enhanced by guanine,
      cytosine, and adenine, respectively, and by derivatives thereof, suggesting a
      transient Watson-Click base pairing between an enhancer molecule and the
      nucleotide to be incorporated. In the presence of some additives (GMP and GDP for
      C-tailing and CMP for G-tailing), the tail length increased continuously,
      resulting in tail lengths of 7 to 15 (GMP and GDP) or 13 to 22 (CMP) nucleotides.
      Among the compounds that do not induce continuous addition, adenosine,
      deoxycytidine, and deoxyguanosine mostly enhanced T-, G-, and C-tailings,
      respectively. The enhancing chemicals described here will improve the feasibility
      of N-tailing by MMLV-RT in various biotechnological applications.

PMID- 28747697
TI  - Live reef fish displaying physiological evidence of cyanide poisoning are still
      traded in the EU marine aquarium industry.
AB  - The illegal use of cyanide poisoning to supply live reef fish to several markets
      is one of the main threats to coral reefs conservation in the Indo-Pacific. The
      present study performed the first survey ever monitoring the marine aquarium
      trade in the EU for the presence of physiological evidence consistent with
      cyanide poisoning in live reef fish. This survey was also the first one worldwide
      employing a non-invasive sampling approach. Nearly 15% of the fish screened
      displayed physiological evidence of being illegally collected using cyanide
      poisoning (by testing positive for the presence of the thiocyanate anion (SCN-)
      in their urine). The efforts promoted so far to completely eradicate cyanide
      caught fish from the marine aquarium trade have not been effective, as our
      results suggest that their prevalence in the trade is in line with data reported
      nearly two decades ago. A new paradigm is urgently needed to effectively ban
      cyanide caught fish from the marine aquarium trade.

PMID- 28747696
TI  - Underestimated Male Prevalence of Primary Biliary Cholangitis in China: Results
      of a 16-yr cohort study involving 769 patients.
AB  - For primary biliary cholangitis (PBC), a sex ratio was reported to be
      significantly lower than previously cited in the West; we sought to evaluate sex
      ratio and long-term outcomes in PBC by studying a PBC cohort at a high-volume
      hospital from January 2001 to July 2016. A retrospective analysis including 769
      PBC patients was conducted. The gender ratio was 6.1:1. Of the patients, 30.6%
      had one or more extrahepatic autoimmune (EHA) conditions. The proportion of
      patients with decompensated PBC at diagnosis increased from 25.0% in period 1 to
      47.0% in period 4 (p < 0.05). Of the 420 patients without complications on
      presentation, the Kaplan-Meier estimate revealed distinct outcomes between non
      cirrhotic PBC and cirrhotic PBC, with estimated mean survival times of 145.1
      months and 104.5 months, respectively (p < 0.001). According to a subgroup
      analysis, gender and anti-mitochondrial antibody (AMA) status did not affect long
      term prognosis, whereas patients with EHA conditions showed better prognoses.
      This study reveals evolving trends in male prevalence similar to their Western
      counterparts. Cirrhotic PBC patients were distinct from those with non-cirrhotic
      PBC at diagnosis based on difference in long-term outcome.

PMID- 28747698
TI  - Adjustable multicolor up-energy conversion in light-luminesce in Tb3+/Tm3+/Yb3+
      co-doped oxyfluorifFde glass-ceramics containing Ba2LaF7 nanocrystals.
AB  - Transparent oxyfluoride glasses with highly efficient up-energy conversion (UEC)
      luminescence were developed in the 45SiO2-15Al2O3-12Na2CO3-21BaF2-7LaF3-xTbF3
      yTmF3-zYbF3 composition (in mol%), and structural investigation by X-ray
      diffraction (XRD) and transmission electron microscopy (TEM) confirmed the
      formation of face-centered cubic Ba2LaF7 nanocrystals. The colors of UEC
      luminescences could be tuned easily by adjusting the concentration of doped rare
      earth ions and the excitation power of laser simultaneously. The relationship
      between the emission intensity of Tb3+/Tm3+/Yb3+ co-doped oxyfluoride glass
      ceramics and the excitation pump power revealed that three-photon and two-photon
      absorptions predominated in the conversion process from the infrared into blue
      and red luminescences, respectively. A novel UEC mechanism of red emission from
      Tm3+ was proposed, energy transfers from Yb3+ to Tm3+ and Tb3+ and from Tm3+ to
      Tb3+ were evidenced. The possible mechanism responsible for the color variation
      of UEC in Tb3+/Tm3+/Yb3+ co-doped was discussed.

PMID- 28747699
TI  - OsFH15, a class I formin, interacts with microfilaments and microtubules to
      regulate grain size via affecting cell expansion in rice.
AB  - Grain size is an important agronomic trait determining rice yield and is mainly
      restricted by spikelet hull size. However, it remains largely unknown how the
      spikelet hull size is regulated. In this study, OsFH15, a class I formin protein
      in Oryza sativa, was found to be able to regulate the size of cells and spikelet
      hull. OsFH15-Cas9 and OsFH15-RNAi mutants had decreased grain size with reduced
      cell length, cell width and cell area of inner epidermal cells of the lemma
      compared with wild-type plants. By contrast, OsFH15-overexpressed plants had
      increased grain size with larger cells, as well as more abundant microtubules
      (MTs) and actin filaments (AFs) arrays. OsFH15 was mainly expressed in shoot
      apical meristem (SAM), spikelets, spikelet hulls and seeds in rice. In vitro
      biochemical experiments showed that OsFH15 can efficiently nucleate actin
      polymerization with or without profilin, can cap the barbed end of AFs, and can
      bind and bundle both AFs and MTs. OsFH15 can also crosslink AFs with MTs, and
      preferentially bind MTs to AFs. These results demonstrated that OsFH15 played an
      important role in grain-size control by affecting cell expansion through
      regulating AFs and MTs.

PMID- 28747700
TI  - Association of pre-operative estimated GFR on post-operative pulmonary
      complications in laparoscopic surgeries.
AB  - Despite a large body of evidence showing the pandemic of chronic kidney disease,
      the impact of pre-operative kidney function on the risk of post-operative
      pulmonary complications (PPCs) is not well known. We used multivariable logistic
      regression analyses with 3-level hierarchical adjustments to identify the
      association of pre-operative estimated glomerular filtration rate (eGFR) with
      PPCs in laparoscopic surgeries. Among 452,213 patients between 2005 and 2013 in
      the American College of Surgeons National Surgical Quality Improvement Program
      (ACS-NSQIP) Database, a total of 3,727 patients (0.9%) experienced PPCs. We found
      a gradient association between lower eGFR and higher likelihood of PPCs in the
      unadjusted model. In the case-mix adjusted model, a reverse-J-shaped association
      was observed; a small albeit significant association with the highest eGFR
      category emerged. Further adjustment slightly attenuated these associations, but
      the PPCs risk in the eGFR groups of <30, 30-60, and >=120 mL/min/1.73 m2 remained
      significant: odds ratios (95% confidence intervals) of 1.82 (1.54-2.16), 1.38
      (1.24-1.54), and 1.28 (1.07-1.53), respectively (reference: 90-120 mL/min/1.73
      m2). Our findings propose a need for careful pre-operative evaluation of
      cardiovascular and pulmonary functions and post-operative fluid management among
      patients with not only lower but also very high eGFR.

PMID- 28747701
TI  - Dietary patterns reflecting healthy food choices are associated with lower serum
      LPS activity.
AB  - Gram-negative bacteria-derived lipopolysaccharides (LPS) are associated with
      various negative health effects. Whether diet is associated with LPS, is an
      understudied phenomenon. We investigated the association between diet and serum
      LPS activity in 668 individuals with type 1 diabetes in the FinnDiane Study.
      Serum LPS activity was determined using the Limulus Amoebocyte Lysate assay. Diet
      was assessed with a food frequency questionnaire (FFQ) section of a diet
      questionnaire and a food record. The food record was used to calculate energy,
      macronutrient, and fibre intake. In a multivariable model, energy, macronutrient,
      or fibre intake was not associated with the LPS activity. Using factor analysis,
      we identified seven dietary patterns from the FFQ data ("Sweet", "Cheese",
      "Fish", "Healthy snack", "Vegetable", "Traditional", and "Modern"). In a
      multivariable model, higher factor scores of the Fish, Healthy snack, and Modern
      patterns predicted lower LPS activity. The validity of the diet questionnaire was
      also investigated. The questionnaire showed reasonable relative validity against
      a 6-day food record. The two methods classified participants into the dietary
      patterns better than expected by chance. In conclusion, healthy dietary choices,
      such as consumption of fish, fresh vegetables, and fruits and berries may be
      associated with positive health outcomes by reducing systemic endotoxaemia.

PMID- 28747702
TI  - Movement Pattern of Scapular Dyskinesis in Symptomatic Overhead Athletes.
AB  - This study investigated the characteristics of arm elevation via principal
      component analysis in symptomatic overhead athletes with scapular dyskinesis. One
      hundred-thirty-four overhead athletes with scapular dyskinesis [24: inferior
      angle prominence (pattern I); 46: medial border prominence (pattern II), 64:
      pattern I + II] were evaluated by three-dimensional electromagnetic motion and
      electromyography to record the scapular kinematics (upward rotation/posterior
      tipping/exterior rotation) and muscle activation (upper trapezius: UT; middle
      trapezius: MT; lower trapezius: LT; serratus anterior: SA) during lowering phase
      of arm elevation. The results showed: (1) for pattern I and II, the first 3
      principal component (PCs) explained 41.4% and 42.6% of total variance of
      movement; (2) the first PCs were correlated with MT, LT activity (r = 0.41~0.61)
      and upward rotation, posterior tipping (r = -0.59~-0.33) in pattern I, and UT,
      MT, SA (r = 0.30~0.70) activity in pattern II; (3) contour plots of muscle
      activity demonstrated that muscle activities varied with dyskinesis patterns. In
      summary, for the pattern I, the major characteristics are coactivation of MT and
      LT and corresponding scapular posterior tipping and upward rotation. For the
      pattern II, the major characteristics are coactivation of UT, MT and SA without
      corresponding scapular external rotation.

PMID- 28747703
TI  - Linking the morphological and metabolomic response of Lactuca sativa L exposed to
      emerging contaminants using GC * GC-MS and chemometric tools.
AB  - The occurrence of contaminants of emerging concern (CECs) in irrigation waters
      (up to low MUg L-1) and irrigated crops (ng g-1 in dry weight) has been reported,
      but the linkage between plant morphological changes and plant metabolomic
      response has not yet been addressed. In this study, a non-targeted metabolomic
      analysis was performed on lettuce (Lactuca sativa L) exposed to 11 CECs
      (pharmaceuticals, personal care products, anticorrosive agents and surfactants)
      by irrigation. The plants were watered with different CEC concentrations (0-50 ug
      L-1) for 34 days under controlled conditions and then harvested, extracted,
      derivatised and analysed by comprehensive two-dimensional gas chromatography
      coupled to a time-of-flight mass spectrometer (GC * GC-TOFMS). The resulting raw
      data were analysed using multivariate curve resolution (MCR) and partial least
      squares (PLS) methods. The metabolic response indicates that exposure to CECs at
      environmentally relevant concentrations (0.05 ug L-1) can cause significant
      metabolic alterations in plants (carbohydrate metabolism, the citric acid cycle,
      pentose phosphate pathway and glutathione pathway) linked to changes in
      morphological parameters (leaf height, stem width) and chlorophyll content.

PMID- 28747704
TI  - Comprehensive molecular analysis of arginase-encoding genes in common wheat and
      its progenitor species.
AB  - Arginase (ARG) contributes to nitrogen remobilization by conversion of arginine
      to ornithine and urea. However, wheat ARG genes have not yet been identified.
      Here we isolated and characterized ARG genes from wheat and its progenitor
      species and found that a single copy was present in wheat progenitors. Three
      common wheat ARG genes of TaARG-2AS, TaARG-2BS, and TaARG-2DS were experimentally
      assigned to the short arms of the group 2 chromosomes. We found an in-frame stop
      codon in TaARG-2AS, but not in the other two genes. The highest expression was
      detected in stems and sheaths for TaARG-2BS and in leaves for TaARG-2DS. Both
      genes have similar expression trend in different developmental stages, peaking at
      booting and grain filling stages. TaARG-2BS transcript was induced by high
      salinity and drought, whereas TaARG-2DS was induced by drought only, but neither
      of them were induced by low temperature. In addition, both genes showed analogous
      expression pattern upon powdery mildew (PM) infection in the resistant line
      Pm97033, with TaARG-2BS induced greatly at 72 h post PM infection. In contrast,
      no obvious transcripts were accumulated for TaARG-2DS in the PM susceptible line
      Wan7107. Monocot ARGs have more conserved mitochondrion-targeting signals and are
      more evolutionarily conserved than dicot ARGs.

PMID- 28747705
TI  - Soil nutritional status and biogeography influence rhizosphere microbial
      communities associated with the invasive tree Acacia dealbata.
AB  - Invasiveness and the impacts of introduced plants are known to be mediated by
      plant-microbe interactions. Yet, the microbial communities associated with
      invasive plants are generally poorly understood. Here we report on the first
      comprehensive investigation of the bacterial and fungal communities inhabiting
      the rhizosphere and the surrounding bulk soil of a widespread invasive tree,
      Acacia dealbata. Amplicon sequencing data indicated that rhizospheric microbial
      communities differed significantly in structure and composition from those of the
      bulk soil. Two bacterial (Alphaproteobacteria and Gammaproteobacteria) and two
      fungal (Pezizomycetes and Agaricomycetes) classes were enriched in the
      rhizosphere compared with bulk soils. Changes in nutritional status, possibly
      induced by A. dealbata, primarily shaped rhizosphere soil communities. Despite a
      high degree of geographic variability in the diversity and composition of
      microbial communities, invasive A. dealbata populations shared a core of
      bacterial and fungal taxa, some of which are known to be involved in N and P
      cycling, while others are regarded as plant pathogens. Shotgun metagenomic
      analysis also showed that several functional genes related to plant growth
      promotion were overrepresented in the rhizospheres of A. dealbata. Overall,
      results suggest that rhizosphere microbes may contribute to the widespread
      success of this invader in novel environments.

PMID- 28747706
TI  - Titanium Dioxide Engineered for Near-dispersionless High Terahertz Permittivity
      and Ultra-low-loss.
AB  - Realising engineering ceramics to serve as substrate materials in high
      performance terahertz(THz) that are low-cost, have low dielectric loss and near
      dispersionless broadband, high permittivity, is exceedingly demanding. Such
      substrates are deployed in, for example, integrated circuits for synthesizing and
      converting nonplanar and 3D structures into planar forms. The Rutile form of
      titanium dioxide (TiO2) has been widely accepted as commercially economical
      candidate substrate that meets demands for both low-loss and high permittivities
      at sub-THz bands. However, the relationship between its mechanisms of dielectric
      response to the microstructure have never been systematically investigated in
      order to engineer ultra-low dielectric-loss and high value, dispersionless
      permittivities. Here we show TiO2 THz dielectrics with high permittivity (ca.
      102.30) and ultra-low loss (ca. 0.0042). These were prepared by insight gleaned
      from a broad use of materials characterisation methods to successfully engineer
      porosities, second phase, crystallography shear-planes and oxygen vacancies
      during sintering. The dielectric loss achieved here is not only with negligible
      dispersion over 0.2-0.8 THz, but also has the lowest value measured for known
      high-permittivity dielectrics. We expect the insight afforded by this study will
      underpin the development of subwavelength-scale, planar integrated circuits,
      compact high Q-resonators and broadband, slow-light devices in the THz band.

PMID- 28747707
TI  - The cryo-EM structure of gastric H+,K+-ATPase with bound BYK99, a high-affinity
      member of K+-competitive, imidazo[1,2-a]pyridine inhibitors.
AB  - The gastric proton pump H+,K+-ATPase acidifies the gastric lumen, and thus its
      inhibitors, including the imidazo[1,2-a]pyridine class of K+-competitive acid
      blockers (P-CABs), have potential application as acid-suppressing drugs. We
      determined the electron crystallographic structure of H+,K+-ATPase at 6.5 A
      resolution in the E2P state with bound BYK99, a potent P-CAB with a restricted
      ring structure. The BYK99 bound structure has an almost identical profile to that
      of a previously determined structure with bound SCH28080, the original P-CAB
      prototype, but is significantly different from the previously reported P-CAB-free
      form, illustrating a common conformational change is required for P-CAB binding.
      The shared conformational changes include a distinct movement of transmembrane
      helix 2 (M2), from its position in the previously reported P-CAB-free form, to a
      location proximal to the P-CAB binding site in the present BYK99-bound structure.
      Site-specific mutagenesis within M2 revealed that D137 and N138, which face the P
      CAB binding site in our model, significantly affect the inhibition constant (K i)
      of P-CABs. We also found that A335 is likely to be near the bridging nitrogen at
      the restricted ring structure of the BYK99 inhibitor. These provide clues to
      elucidate the binding site parameters and mechanism of P-CAB inhibition of
      gastric acid secretion.

PMID- 28747708
TI  - Singularity in the matrix of the coupled Gross-Pitaevskii equations and the
      related state-transitions in three-species condensates.
AB  - An approach is proposed to solve the coupled Gross-Pitaevskii equations (CGP) of
      the 3-species BEC in an analytical way under the Thomas-Fermi approximation
      (TFA). It was found that, when the strength of a kind of interaction increases
      and crosses over a critical value, a specific type of state-transition will occur
      and will cause a jump in the total energy. Due to the jump, the energy of the
      lowest symmetric state becomes considerably higher. This leaves a particular
      opportunity for the lowest asymmetric state to replace the symmetric states as
      the ground state. It was further found that the critical values are related to
      the singularity of either the matrix or a sub-matrix of the CGP. These critical
      values are not arising from the TFA but inherent in the CGP, and they can be
      analytically expressed. Furthermore, a model (in which two kinds of atoms
      separated from each other asymmetrically) has been proposed for the evaluation of
      the energy of the lowest asymmetric state. With this model the emergence of the
      asymmetric ground state is numerically confirmed under the TFA. The theoretical
      formalism of this paper is quite general and can be generalized for BEC with more
      than three species.

PMID- 28747709
TI  - Trimethylamine N-oxide abolishes the chaperone activity of alpha-casein: an
      intrinsically disordered protein.
AB  - Osmolytes (small molecules that help in circumventing stresses) are known to
      promote protein folding and prevent aggregation in the case of globular proteins.
      However, the effect of such osmolytes on the structure and function of
      intrinsically disordered proteins (IDPs) has not been clearly understood. Here we
      have investigated the effect of methylamine osmolytes on alpha-casein (an IDP
      present in mammalian milk) and discovered that TMAO (Trimethylamine-N-oxide) but
      not other methylamines renders alpha-casein functionless. We observed that the
      loss of chaperone activity of alpha-casein in presence of TMAO was due to the
      induction of an unstable aggregation-prone intermediate. The results indicate
      that different osmolytes may have different structural and functional
      consequences on IDPs, and therefore might have clinical implications for a large
      number of human diseases (e.g., amyloidosis, cancer, diabetes, and
      neurodegeneration) where IDPs are involved.

PMID- 28747710
TI  - A high-content image analysis approach for quantitative measurements of
      chemosensitivity in patient-derived tumor microtissues.
AB  - Organotypic, three-dimensional (3D) cancer models have enabled investigations of
      complex microtissues in increasingly realistic conditions. However, a drawback of
      these advanced models remains the poor biological relevance of cancer cell lines,
      while higher clinical significance would be obtainable with patient-derived cell
      cultures. Here, we describe the generation and data analysis of 3D microtissue
      models from patient-derived xenografts (PDX) of non-small cell lung carcinoma
      (NSCLC). Standard of care anti-cancer drugs were applied and the altered
      multicellular morphologies were captured by confocal microscopy, followed by
      automated image analyses to quantitatively measure phenotypic features for high
      content chemosensitivity tests. The obtained image data were thresholded using a
      local entropy filter after which the image foreground was split into local
      regions, for a supervised classification into tumor or fibroblast cell types.
      Robust statistical methods were applied to evaluate treatment effects on growth
      and morphology. Both novel and existing computational approaches were compared at
      each step, while prioritizing high experimental throughput. Docetaxel was found
      to be the most effective drug that blocked both tumor growth and invasion. These
      effects were also validated in PDX tumors in vivo. Our research opens new avenues
      for high-content drug screening based on patient-derived cell cultures, and for
      personalized chemosensitivity testing.

PMID- 28747711
TI  - A systems approach to a spatio-temporal understanding of the drought stress
      response in maize.
AB  - Crops are often subjected to periods of drought stress during their life cycle.
      However, how stress response mechanisms contribute to the crosstalk between
      stress signaling pathways and developmental signaling pathways is still unknown.
      We built a gene co-expression network from a spatio-temporal transcriptomic map
      of the drought stress response in maize (Zea mays), profiled from three tissues
      and four developmental stages and characterized hub genes associated with
      duplication events, selection, and regulatory networks. Co-expression analysis
      grouped drought-response genes into ten modules, covering 844 highly connected
      genes (hub genes). Of these, 15.4% hub genes had diverged by whole-genome
      duplication events and 2.5% might then have been selected during natural
      domestication and artificial improvement processes, successively. We identified
      key transcription factor hubs in a transcriptional regulatory network, which may
      function as a crosstalk mechanism between drought stress and developmental
      signalling pathways in maize. Understanding the evolutionary biases that have
      evolved to enhance drought adaptation lays the foundation for further dissection
      of crosstalk between stress signalling pathways and developmental signalling
      pathways in maize, towards molecular design of new cultivars with desirable yield
      and greater stress tolerance.

PMID- 28747712
TI  - 2-Oxoadenosine induces cytotoxicity through intracellular accumulation of 2-oxo
      ATP and depletion of ATP but not via the p38 MAPK pathway.
AB  - 2-Oxoadenosine (2-oxo-Ado), an oxidized form of adenosine, is cytotoxic and
      induces growth arrest and cell death, which has potential as an anti-cancer drug.
      However, it is not well understood how 2-oxo-Ado exerts its cytotoxicity. We
      examined the effects of 2-oxo-Ado on non-tumour cells, namely immortalized mouse
      embryonic fibroblast lines, and investigated mechanisms by which 2-oxo-Ado exerts
      its cytotoxicity. We found that cell death induced by 2-oxo-Ado is classical
      caspase-dependent apoptosis, and requires its sequential intracellular
      phosphorylation catalysed by adenosine kinase (ADK) and adenylate kinase 2,
      resulting in intracellular accumulation of 2-oxo-ATP accompanied by accumulation
      of 2-oxo-Ado in RNA and depletion of ATP. Moreover, we showed that overexpression
      of MTH1, an oxidized purine nucleoside triphosphatase, prevents 2-oxo-Ado-induced
      cytotoxicity accompanied by suppression of accumulation of both intracellular 2
      oxo-ATP and 2-oxo-Ado in RNA and recovery of ATP levels. We also found that 2-oxo
      Ado activates the p38 MAPK pathway. However, siRNAs against Mkk3 and Mkk6, or
      treatment with several p38 MAPK inhibitors, except SB203580, did not prevent the
      cytotoxicity. SB203580 prevented intracellular phosphorylation of 2-oxo-Ado to 2
      oxo-AMP, and an in vitro ADK assay revealed that SB203580 directly inhibits ADK
      activity, suggesting that some of the effects of SB203580 may depend on ADK
      inhibition.

PMID- 28747713
TI  - Overcoming blood brain barrier with a dual purpose Temozolomide loaded
      Lactoferrin nanoparticles for combating glioma (SERP-17-12433).
AB  - Targeted delivery of drugs to the brain is challenging due to the restricted
      permeability across the blood brain barrier (BBB). Gliomas are devastating
      cancers and their positive treatment outcome using Temozolomide (TMZ) is limited
      due to its short plasma half-life, systemic toxicity and limited access through
      the blood-brain barrier (BBB). Nanoparticles made of Lactoferrin (Lf) protein,
      have been shown to enhance the pharmacological properties of drugs. Here, we
      report the specific ability of Lf nanoparticles to cross BBB and target over
      expressed Lf receptors on glioma for enhanced TMZ delivery. TMZ-loaded Lf
      nanoparticles (TMZ-LfNPs) were prepared by our previously reported sol-oil
      method. While the Lf protein in the NP matrix aids in transcytosis across the BBB
      and preferential tumor cell uptake, the pH responsiveness leads to TMZ release
      exclusively in the tumor microenvironment. Delivery through LfNPs results in an
      enhanced and sustained intracellular concentration of TMZ in GL261 cells in vitro
      along with improving its in vivo pharmacokinetics and brain accumulation. TMZ
      LfNPs treatment results in a significant reduction of tumor volume, higher tumor
      cell apoptosis and improved median survival in glioma bearing mice. These results
      demonstrate that LfNPs present an efficient TMZ delivery platform for an
      effective treatment of gliomas.

PMID- 28747714
TI  - Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection
      in Adults Hospitalized with Respiratory Illness.
AB  - Lower respiratory tract infection (LRTI) commonly causes hospitalization in
      adults. Because bacterial diagnostic tests are not accurate, antibiotics are
      frequently prescribed. Peripheral blood gene expression to identify subjects with
      bacterial infection is a promising strategy. We evaluated whole blood profiling
      using RNASeq to discriminate infectious agents in adults with microbiologically
      defined LRTI. Hospitalized adults with LRTI symptoms were recruited. Clinical
      data and blood was collected, and comprehensive microbiologic testing performed.
      Gene expression was measured using RNASeq and qPCR. Genes discriminatory for
      bacterial infection were identified using the Bonferroni-corrected Wilcoxon test.
      Constrained logistic models to predict bacterial infection were fit using
      screened LASSO. We enrolled 94 subjects who were microbiologically classified; 53
      as "non-bacterial" and 41 as "bacterial". RNAseq and qPCR confirmed significant
      differences in mean expression for 10 genes previously identified as
      discriminatory for bacterial LRTI. A novel dimension reduction strategy selected
      three pathways (lymphocyte, alpha-linoleic acid metabolism, IGF regulation)
      including eleven genes as optimal markers for discriminating bacterial infection
      (naive AUC = 0.94; nested CV-AUC = 0.86). Using these genes, we constructed a
      classifier for bacterial LRTI with 90% (79% CV) sensitivity and 83% (76% CV)
      specificity. This novel, pathway-based gene set displays promise as a method to
      distinguish bacterial from nonbacterial LRTI.

PMID- 28747715
TI  - ATP-dependent modulation of MgtE in Mg2+ homeostasis.
AB  - Magnesium is an essential ion for numerous physiological processes. MgtE is a
      Mg2+ selective channel involved in the maintenance of intracellular Mg2+
      homeostasis, whose gating is regulated by intracellular Mg2+ levels. Here, we
      report that ATP binds to MgtE, regulating its Mg2+-dependent gating. Crystal
      structures of MgtE-ATP complex show that ATP binds to the intracellular CBS
      domain of MgtE. Functional studies support that ATP binding to MgtE enhances the
      intracellular domain affinity for Mg2+ within physiological concentrations of
      this divalent cation, enabling MgtE to function as an in vivo Mg2+ sensor. ATP
      dissociation from MgtE upregulates Mg2+ influx at both high and low intracellular
      Mg2+ concentrations. Using site-directed mutagenesis and structure based
      electrophysiological and biochemical analyses, we identify key residues and main
      structural changes involved in the process. This work provides the molecular
      basis of ATP-dependent modulation of MgtE in Mg2+ homeostasis.MgtE is an Mg2+
      transporter involved in Mg2+ homeostasis. Here, the authors report that ATP
      regulates the Mg+2-dependent gating of MgtE and use X-ray crystallography
      combined with functional studies to propose the molecular mechanisms involved in
      this process.

PMID- 28747716
TI  - Burn-induced muscle metabolic derangements and mitochondrial dysfunction are
      associated with activation of HIF-1alpha and mTORC1: Role of protein
      farnesylation.
AB  - Metabolic derangements are a clinically significant complication of major trauma
      (e.g., burn injury) and include various aspects of metabolism, such as insulin
      resistance, muscle wasting, mitochondrial dysfunction and hyperlactatemia.
      Nonetheless, the molecular pathogenesis and the relation between these diverse
      metabolic alterations are poorly understood. We have previously shown that burn
      increases farnesyltransferase (FTase) expression and protein farnesylation and
      that FTase inhibitor (FTI) prevents burn-induced hyperlactatemia, insulin
      resistance, and increased proteolysis in mouse skeletal muscle. In this study, we
      found that burn injury activated mTORC1 and hypoxia-inducible factor (HIF)
      1alpha, which paralleled dysfunction, morphological alterations (i.e.,
      enlargement, partial loss of cristae structure) and impairment of respiratory
      supercomplex assembly of the mitochondria, and ER stress. FTI reversed or
      ameliorated all of these alterations in burned mice. These findings indicate that
      these burn-induced changes, which encompass various aspects of metabolism, may be
      linked to one another and require protein farnesylation. Our results provide
      evidence of involvement of the mTORC1-HIF-1alpha pathway in burn-induced
      metabolic derangements. Our study identifies protein farnesylation as a potential
      hub of the signaling network affecting multiple aspects of metabolic alterations
      after burn injury and as a novel potential molecular target to improve the
      clinical outcome of severely burned patients.

PMID- 28747717
TI  - Contextual connectivity: A framework for understanding the intrinsic dynamic
      architecture of large-scale functional brain networks.
AB  - Investigations of the human brain's connectomic architecture have produced two
      alternative models: one describes the brain's spatial structure in terms of
      static localized networks, and the other describes the brain's temporal structure
      in terms of dynamic whole-brain states. Here, we used tools from connectivity
      dynamics to develop a synthesis that bridges these models. Using resting fMRI
      data, we investigated the assumptions undergirding current models of the human
      connectome. Consistent with state-based models, our results suggest that static
      localized networks are superordinate approximations of underlying dynamic states.
      Furthermore, each of these localized, dynamic connectivity states is associated
      with global changes in the whole-brain functional connectome. By nesting
      localized dynamic connectivity states within their whole-brain contexts, we
      demonstrate the relative temporal independence of brain networks. Our assay for
      functional autonomy of coordinated neural systems is broadly applicable, and our
      findings provide evidence of structure in temporal state dynamics that
      complements the well-described static spatial organization of the brain.

PMID- 28747718
TI  - Predicting the functional consequences of non-synonymous single nucleotide
      polymorphisms in IL8 gene.
AB  - Here we report an in-silico approach for identification, characterization and
      validation of deleterious non-synonymous SNPs (nsSNPs) in the interleukin-8 gene
      using three steps. In first step, sequence homology-based genetic analysis of a
      set of 50 coding SNPs associated with 41 rsIDs using SIFT (Sorting Intolerant
      from Tolerant) and PROVEAN (Protein Variation Effect Analyzer) identified 23
      nsSNPs to be putatively damaging/deleterious in at least one of the two tools
      used. Subsequently, structure-homology based PolyPhen-2 (Polymorphism
      Phenotyping) analysis predicted 9 of 23 nsSNPs (K4T, E31A, E31K, S41Y, I55N,
      P59L, P59S, L70P and V88D) to be damaging. According to the conditional
      hypothesis for the study, only nsSNPs that score damaging/deleterious prediction
      in both sequence and structural homology-based approach will be considered as
      'high-confidence' nsSNPs. In step 2, based on conservation of amino acid
      residues, stability analysis, structural superimposition, RSMD and docking
      analysis, the possible structural-functional relationship was ascertained for
      high-confidence nsSNPs. Finally, in a separate analysis (step 3), the IL-8
      deregulation has also appeared to be an important prognostic marker for detection
      of patients with gastric and lung cancer. This study, for the first time,
      provided in-depth insights on the effects of amino acid substitutions on IL-8
      protein structure, function and disease association.

PMID- 28747719
TI  - Multi-year predictability of climate, drought, and wildfire in southwestern North
      America.
AB  - Past severe droughts over North America have led to massive water shortages and
      increases in wildfire frequency. Triggering sources for multi-year droughts in
      this region include randomly occurring atmospheric blocking patterns, ocean
      impacts on atmospheric circulation, and climate's response to anthropogenic
      radiative forcings. A combination of these sources translates into a difficulty
      to predict the onset and length of such droughts on multi-year timescales. Here
      we present results from a new multi-year dynamical prediction system that
      exhibits a high degree of skill in forecasting wildfire probabilities and drought
      for 10-23 and 10-45 months lead time, which extends far beyond the current
      seasonal prediction activities for southwestern North America. Using a state-of
      the-art earth system model along with 3-dimensional ocean data assimilation and
      by prescribing the external radiative forcings, this system simulates the
      observed low-frequency variability of precipitation, soil water, and wildfire
      probabilities in close agreement with observational records and reanalysis data.
      The underlying source of multi-year predictability can be traced back to
      variations of the Atlantic/Pacific sea surface temperature gradient, external
      radiative forcings, and the low-pass filtering characteristics of soils.

PMID- 28747720
TI  - Mitochondrial Genomes of Two Bombycoidea Insects and Implications for Their
      Phylogeny.
AB  - The mitochondrial genome (mt genome) provides important information for
      understanding molecular evolution and phylogenetics. As such, the two complete mt
      genomes of Ampelophaga rubiginosa and Rondotia menciana were sequenced and
      annotated. The two circular genomes of A. rubiginosa and R. menciana are 15,282
      and 15,636 bp long, respectively, including 13 protein-coding genes (PCGs), two
      rRNA genes, 22 tRNA genes and an A + T-rich region. The nucleotide composition of
      the A. rubiginosa mt genome is A + T rich (81.5%) but is lower than that of R.
      menciana (82.2%). The AT skew is slightly positive and the GC skew is negative in
      these two mt genomes. Except for cox1, which started with CGA, all other 12PCGs
      started with ATN codons. The A + T-rich regions of A. rubiginosa and R. menciana
      were 399 bp and 604 bp long and consist of several features common to Bombycoidea
      insects. The order and orientation of A. rubiginosa and R. menciana mitogenomes
      with the order trnM-trnI-trnQ-nad2 is different from the ancestral insects in
      which trnM is located between trnQ and nad2 (trnI-trnQ-trnM-nad2). Phylogenetic
      analyses indicate that A. rubiginosa belongs in the Sphingidae family, and R.
      menciana belongs in the Bombycidae family.

PMID- 28747721
TI  - Downregulation of Interferon-beta and Inhibition of TLR3 Expression are
      associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome.
AB  - Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious
      disease with high mortality and increasing prevalence in the East Asia. Though
      the etiological agent has been identified as a novel Bunyavirus, cellular
      mechanisms of viral pathogenesis and host immune response to SFTS virus infection
      remain unknown. A comprehensive study was conducted on a cohort of 70 patients on
      clinical manifestations, viral loads, modulation of cytokines, serum interferon
      level, immune related gene expression in peripheral blood cells, and dynamic
      changes of circulating dendritic cells during the acute phase of SFTSV infection.
      We found that high level viremia, reduced platelets, coagulation dysfunction,
      multi-organ injuries, elevated IL-6 and TNF-alpha were closely associated with
      the aggravation of SFTS. In addition, we demonstrated strong correlations between
      disease severity and the decline of serum IFN-beta and IL-1beta level, reduction
      of myeloid dendritic cells (mDCs) and suppressed Toll like receptor 3 expression
      in monocytes and mDCs. In general, dysfunction of innate immune response and
      cytokine storm are both involved in the pathogenesis of SFTS. Reduction of
      myeloid DCs contributes to the fatal outcome of SFTS virus infection, and the
      regulation of TLR3 could probably be the mechanism.

PMID- 28747722
TI  - Assessing Screening Guidelines for Cardiovascular Disease Risk Factors using
      Routinely Collected Data.
AB  - This study investigates if laboratory data can be used to assess whether
      physician-retesting patterns are in line with established guidelines, and if
      these guidelines identify deteriorating patients in a timely manner. A total of
      7594 patients with high cholesterol were studied, along with 2764 patients with
      diabetes. More than 90% of borderline high cholesterol patients are retested
      within the 3 year recommended period, however less than 75% of pre-diabetic
      patients have repeated tests within the suggested 1-year time frame. Patients
      with borderline high cholesterol typically progress to full high cholesterol in 2
      3 years, and pre-diabetic patients progress to full diabetes in 1-2 years. Data
      from routinely ordered laboratory tests can be used to monitor adherence to
      clinical guidelines. These data may also be useful in the design of adaptive
      testing strategies that reduce unnecessary testing, while ensuring that patient
      deterioration is identified in a timely manner. Established guidelines for
      testing of total serum cholesterol for hypercholesterolemia are appropriate and
      are well-adhered to, whereas guidelines for glycated hemoglobin A1c testing for
      type 2 diabetes mellitus could be improved to bring them in line with current
      practice and avoid unnecessary testing.

PMID- 28747723
TI  - Thermal management of micro-scale inorganic light-emittng diodes on an
      orthotropic substrate for biointegrated applications.
AB  - The orthotropic material with the in-plane thermal conductivity much larger than
      the off-plane one can control the heat flow direction. This feature provides
      unique benefits in thermal management of micro-scale inorganic light-emitting
      diodes (MU-ILEDs) device for biointegrated applications by helping the heat
      dissipation from MU-ILEDs along the in-plane directions to lower the MU-ILED
      temperature and prevent the heat dissipation to the tissue along the off-plane
      direction to ensure a low tissue temperature. Three-dimensional analytical
      models, accounting for the coupling between the Fourier heat conduction in the MU
      ILED device and the Pennes bioheat transfer in the human skin, are established to
      investigate the thermal behaviors of MU-ILEDs on an orthotropic substrate
      integrated with the human skin. Both the operations of MU-ILEDs in a constant
      mode and pulsed mode are studied. The maximum temperature increases of MU-ILED
      and in the tissue are derived and their dependences on various parameters such as
      the thermal conductivities of the orthotropic substrate, substrate thickness, and
      loading parameters (e.g., duty cycle, pulse period) are investigated. These
      results pave the theoretical foundation for the thermal management of MU-ILED
      devices for biointegrated applications.

PMID- 28747724
TI  - Effects of testosterone and flutamide on reproduction in Brachionus calyciflorus.
AB  - The effects of testosterone and flutamide on reproduction in Brachionus
      calyciflorus were studied. Asexual reproduction in B. calyciflorus was not
      affected by testosterone at different concentrations of flutamide. Flutamide in
      combination with 0, 25, 50, or 75 ug L-1 testosterone had a significant effect on
      mixis rate. The combination of 5 ug L-1 flutamide with 25 ug L-1 or 50 ug L-1
      testosterone resulted in a mixis rate that was 2.2* lower than that with
      flutamide alone. Fertilization rate was significantly decreased by 7.5 ug L-1
      flutamide in combination with 25, 50, or 75 ug L-1 testosterone. The number of
      resting eggs produced per mictic female was significantly lower at all
      concentrations of testosterone. A low concentration of flutamide in combination
      with testosterone resulted in antagonism, increasing the number of resting eggs
      produced. However, when testosterone was combined with a higher concentration of
      flutamide, resting egg production declined. Therefore, long-term exposure to
      either testosterone, flutamide, or a combination of these two compounds may
      significantly reduce resting egg production in rotifers. This implies that
      resting egg production is affected differently by hormone pathways.

PMID- 28747725
TI  - Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner.
AB  - Obesity is a risk factor for many diseases including diabetes, cancer,
      cardiovascular disease, and chronic kidney disease. Obesity is characterized by
      the expansion of white adipose tissue (WAT). Hypertrophy and hyperplasia of
      adipocytes cause tissue hypoxia followed by inflammation and fibrosis. Its
      trigger, preadipocyte differentiation into mature adipocytes, is finely regulated
      by transcription factors, signal molecules, and cofactors. We found that
      echinomycin, a potent HIF-1 inhibitor, completely inhibited adipogenesis in 3T3
      L1 WAT preadipocytes by affecting the early phase of mitotic clonal expansion.
      The dose required to exert the effect was surprisingly low and the time was
      short. Interestingly, its inhibitory effect was independent of HIF-1 pathways.
      Time-course DNA microarray analysis of drug-treated and untreated preadipocytes
      extracted a major transcription factor, CCAAT/enhancer-protein beta, as a key
      target of echinomycin. Echinomycin also inhibited adipogenesis and body weight
      gain in high fat diet mice. These findings highlight a novel role of echinomycin
      in suppressing adipocyte differentiation and offer a new therapeutic strategy
      against obesity and diabetes.

PMID- 28747726
TI  - Association of microRNAs with Argonaute proteins in the malaria mosquito
      Anopheles gambiae after blood ingestion.
AB  - Drastic changes in gene expression occur after adult female mosquitoes take a
      blood meal and use the nutrients for egg maturation. A growing body of evidence
      indicates that microRNAs (miRNAs) contribute to this tightly controlled tissue-
      and stage-specific gene expression. To investigate the role of miRNAs, we
      monitored miRNA expression in the mosquito Anopheles gambiae during the 72-h
      period immediately after blood feeding. We also measured the association of
      miRNAs with Argonaute 1 (Ago1) and Argonaute 2 (Ago2) to assess the functional
      status of individual miRNA species. Overall, 173 mature miRNAs were precipitated
      with Ago1 and Ago2, including 12 new miRNAs, the orthologs of which are found
      thus far only in other Anopheles species. Ago1 is the predominant carrier of
      miRNAs in Anopheles gambiae. The abundance and Ago loading of most of the mature
      miRNAs were relatively stable after blood ingestion. However, miRNAs of the miR
      309/286/2944 cluster were considerably upregulated after blood feeding. Injection
      of the specific antagomir for miR-309 resulted in smaller developing oocytes and
      ultimately fewer eggs. In addition, the Ago association of some miRNAs was not
      proportional to their cellular abundance, suggesting that integration of miRNAs
      into the Ago complexes is regulated by additional mechanisms.

PMID- 28747727
TI  - Metal-free Ternary BCN Nanosheets with Synergetic Effect of Band Gap Engineering
      and Magnetic Properties.
AB  - Introducing the synergy effect of magnetic properties and band gap engineering is
      highly desired for two-dimensional (2D) nanosheets. Here, we prepare metal-free
      ternary 2D carbon (C) doped boron nitride (BN) nanosheets (BCN) with band gap
      engineering and magnetic properties by a synergetic way. The substitutional
      occupation of C atoms, as revealed by X-ray absorption spectrum, in BCN
      nanosheets induces tunable band gap reduction (5.5 eV to 2.6 eV) and intensive
      intrinsic ferromagnetism at room temperature. First-principle calculations also
      reveal that substituted C atoms in BCN nanosheets can broaden the light
      adsorption region and reduce the optical band gap, and ferromagnetic ordering is
      energetically more favorable than antiferromagnetic. This design opens up new
      possibility for synergetic manipulation of exchange interactions and band gap
      engineering in 2D nanostructures.

PMID- 28747728
TI  - Next Generation Ceramic Substrate Fabricated at Room Temperature.
AB  - A ceramic substrate must not only have an excellent thermal performance but also
      be thin, since the electronic devices have to become thin and small in the
      electronics industry of the next generation. In this manuscript, a thin ceramic
      substrate (thickness: 30-70 um) is reported for the next generation ceramic
      substrate. It is fabricated by a new process [granule spray in vacuum (GSV)]
      which is a room temperature process. For the thin ceramic substrates, AlN GSV
      films are deposited on Al substrates and their electric/thermal properties are
      compared to those of the commercial ceramic substrates. The thermal resistance is
      significantly reduced by using AlN GSV films instead of AlN bulk-ceramics in
      thermal management systems. It is due to the removal of a thermal interface
      material which has low thermal conductivity. In particular, the dielectric
      strengths of AlN GSV films are much higher than those of AlN bulk-ceramics which
      are commercialized, approximately 5 times. Therefore, it can be expected that
      this GSV film is a next generation substrate in thermal management systems for
      the high power application.

PMID- 28747729
TI  - Conformational preludes to the latency transition in PAI-1 as determined by
      atomistic computer simulations and hydrogen/deuterium-exchange mass spectrometry.
AB  - Both function and dysfunction of serine protease inhibitors (serpins) involve
      massive conformational change in their tertiary structure but the dynamics
      facilitating these events remain poorly understood. We have studied the dynamic
      preludes to conformational change in the serpin plasminogen activator inhibitor 1
      (PAI-1). We report the first multi-microsecond atomistic molecular dynamics
      simulations of PAI-1 and compare the data with experimental hydrogen/deuterium
      exchange data (HDXMS). The simulations reveal notable conformational flexibility
      of helices D, E and F and major fluctuations are observed in the W86-loop which
      occasionally leads to progressive detachment of beta-strand 2 A from beta-strand
      3 A. An interesting correlation between Calpha-RMSD values from simulations and
      experimental HDXMS data is observed. Helices D, E and F are known to be important
      for the overall stability of active PAI-1 as ligand binding in this region can
      accelerate or decelerate the conformational inactivation. Plasticity in this
      region may thus be mechanistically linked to the conformational change, possibly
      through facilitation of further unfolding of the hydrophobic core, as previously
      reported. This study provides a promising example of how computer simulations can
      help tether out mechanisms of serpin function and dysfunction at a spatial and
      temporal resolution that is far beyond the reach of any experiment.

PMID- 28747730
TI  - Epidemiology and characterization of avian infectious bronchitis virus strains
      circulating in southern China during the period from 2013-2015.
AB  - Two hundred and six strains of avian infectious bronchitis virus (IBV) were
      isolated from chickens showing signs of disease in southern China during the
      period from 2013-2015. The nucleotide and amino acid sequences from the isolated
      field strains were compared to 42 published references. Nucleotide homologies
      ranged from 63.1-99.9% and amino acid homologies ranging from 60.2-100%. At least
      seven IBV genotypes were co-circulating in commercial chicken farms in southern
      China. The IBV isolates were genetically diverse and underwent continuing
      evolution. The QX-type, TW I-type, and 4/91-type were the most common genotypes
      during the three-year observation period and accounted for 88.8% of the isolated
      strains. Notably, the prevalence of the TW I-type strains has been increasing in
      recent years and has become the most common genotype in China. The emergence of
      variant IBV strains can be attributed to recombination. Serologic analysis and
      antigenic 3D cartography of 4 reference and 14 field isolated strains indicated
      the surveyed IBVs had diverse serology types and that the serotype of the
      isolated QX-type and TW I-type strains was distinct from the vaccines strains.
      Therefore, long-term continuing surveillance is necessary for IBV prevention and
      control.

PMID- 28747731
TI  - Dynamical sensitivity control of a single-spin quantum sensor.
AB  - The Nitrogen-Vacancy (NV) defect in diamond is a unique quantum system that
      offers precision sensing of nanoscale physical quantities at room temperature
      beyond the current state-of-the-art. The benchmark parameters for nanoscale
      magnetometry applications are sensitivity, spectral resolution, and dynamic
      range. Under realistic conditions the NV sensors controlled by conventional
      sensing schemes suffer from limitations of these parameters. Here we
      experimentally show a new method called dynamical sensitivity control (DYSCO)
      that boost the benchmark parameters and thus extends the practical applicability
      of the NV spin for nanoscale sensing. In contrast to conventional dynamical
      decoupling schemes, where pi pulse trains toggle the spin precession abruptly,
      the DYSCO method allows for a smooth, analog modulation of the quantum probe's
      sensitivity. Our method decouples frequency selectivity and spectral resolution
      unconstrained over the bandwidth (1.85 MHz-392 Hz in our experiments). Using
      DYSCO we demonstrate high-accuracy NV magnetometry without |2pi| ambiguities, an
      enhancement of the dynamic range by a factor of 4 . 103, and interrogation times
      exceeding 2 ms in off-the-shelf diamond. In a broader perspective the DYSCO
      method provides a handle on the inherent dynamics of quantum systems offering
      decisive advantages for NV centre based applications notably in quantum
      information and single molecule NMR/MRI.

PMID- 28747732
TI  - Possibly scalable solar hydrogen generation with quasi-artificial leaf approach.
AB  - Any solar energy harvesting technology must provide a net positive energy
      balance, and artificial leaf concept provided a platform for solar water
      splitting (SWS) towards that. However, device stability, high photocurrent
      generation, and scalability are the major challenges. A wireless device based on
      quasi-artificial leaf concept (QuAL), comprising Au on porous TiO2 electrode
      sensitized by PbS and CdS quantum dots (QD), was demonstrated to show sustainable
      solar hydrogen (490 +/- 25 umol/h (corresponds to 12 ml H2 h-1) from ~2 mg of
      photoanode material coated over 1 cm2 area with aqueous hole (S2-/SO32-)
      scavenger. A linear extrapolation of the above results could lead to hydrogen
      production of 6 L/h.g over an area of ~23 * 23 cm2. Under one sun conditions, 4.3
      mA/cm2 photocurrent generation, 5.6% power conversion efficiency, and spontaneous
      H2 generation were observed at no applied potential (see S1). A direct coupling
      of all components within themselves enhances the light absorption in the entire
      visible and NIR region and charge utilization. Thin film approach, as in DSSC,
      combined with porous titania enables networking of all the components of the
      device, and efficiently converts solar to chemical energy in a sustainable
      manner.

PMID- 28747733
TI  - Non-ionising UV light increases the optical density of hygroscopic self assembled
      DNA crystal films.
AB  - We report on ultraviolet (UV) light induced increases in the UV optical density
      of thin and optically transparent crystalline DNA films formed through self
      assembly. The films are comprised of closely packed, multi-faceted and sub micron
      sized crystals. UV-Vis spectrophotometry reveals that DNA films with surface
      densities up to 0.031 mg/mm2 can reduce the transmittance of incident UVC and UVB
      light by up to 90%, and UVA transmittance by up to 20%. Subsequent and
      independent film irradiation with either UVA or UVB dosages upwards of 80 J/cm2
      both reduce UV transmittance, with reductions scaling monotonically with UV
      dosage. To date the induction of a hyperchromic effect has been demonstrated
      using heat, pH, high salt mediums, and high energy ionising radiation. Both
      hyperchromicity and increased light scattering could account for the increased
      film optical density after UV irradiation. Additional characterisation of the
      films reveal they are highly absorbent and hygroscopic. When coated on human
      skin, they are capable of slowing water evaporation and keeping the tissue
      hydrated for extended periods of time.

PMID- 28747734
TI  - Reducing Animal Use with a Biotelemetry-Enhanced Murine Model of Sepsis.
AB  - Animal models of sepsis exhibit considerable variability in the temporal
      development of the physiologic response, which reduces the power of studies,
      particularly if interventions are tested at arbitrary time points. We developed a
      biotelemetry-based model of cecal ligation and puncture (CLP) that standardizes
      the testing of time-sensitive therapies to specific criteria of physiologic
      deterioration. In this study we seek to further define the variability in
      physiologic response to CLP sepsis and conduct a cost analysis detailing the
      potential for reducing animal usage. We have further characterized the
      variability in physiologic response after CLP in mice and determined peaks in the
      temporal distribution of points of physiologic decline. Testing therapies at
      physiologic thresholds reduces the variability found in historical fixed time
      based models. Though initial cost is higher with biotelemetry, this is eventually
      offset by the significantly reduced number of mice needed to conduct
      physiologically relevant sepsis experiments.

PMID- 28747735
TI  - Major histocompatibility complex genes partly explain early survival in house
      sparrows.
AB  - Environmental factors and genetic incompatibilities between parents have been
      suggested as important determinants for embryonic mortality and survival. The
      genetic set-up of the immune system, specifically the highly polymorphic major
      histocompatibility complex (MHC) may also influence individual resistance to
      infections. MHC proteins are important for an appropriate adaptive immune
      response and enable T-cells to separate 'self' from 'non-self'. Here we
      investigate the importance of MHC functional diversity for early development in
      birds, more specifically, if offspring survival and body mass or size depends on
      number of different functional MHC alleles, specific functional MHC alleles or
      similarity of MHC alleles in the parents. Unhatched eggs are common in clutches
      of many bird species. In house sparrows (Passer domesticus), embryo and nestling
      mortality can exceed 50%. To control for environmental factors, our study was
      carried out on an aviary population. We found that one specific functional MHC
      allele was associated with reduced nestling survival, which was additionally
      supported by lower body mass and a smaller tarsus when nestlings have been 6 days
      old. Another allele was positively associated with tarsus length at a later
      nestling stage (nestlings 12 days old). These results indicate that MHC alleles
      might influence pathogen resistance or susceptibility.

PMID- 28747736
TI  - Association of UBASH3A gene polymorphism and atopic dermatitis in the Chinese Han
      population.
AB  - Genome-wide association studies have revealed a large number of genetic-risk loci
      for many autoimmune diseases. One clear finding emerging from the published
      genetic studies of autoimmunity is that different autoimmune diseases share
      susceptibility loci. Recent evidence has demonstrated that UBASH3A gene was
      associated with multiple autoimmune diseases. The aim of this study was to
      explore the association between UBASH3A single-nucleotide polymorphisms (SNPs)
      and atopic dermatitis (AD) in a Chinese Han population. In total, three UBASH3A
      SNPs (rs11203203, rs3788013 and rs1893592) were genotyped using TaqMan genotyping
      assays in a Chinese Han population (1012 cases and 1362 controls). Among these
      SNPs, we selected the SNP rs1893592 with association values of P<5 * 10-2 for AD
      in the TaqMan genotyping assay data for further replication in the independent
      Chinese replication samples (1080 cases and 1367 controls) using a Sequenom
      MassARRAY system. We combined the association results in two stages using meta
      analysis. We found that rs1893592 in UBASH3A showed association with AD (P=1.29 *
      10-3, odds ratio=1.16). These results showed that UBASH3A gene SNP is associated
      with susceptibility to AD. Further fine mapping and functional studies will be
      required to identify true causal variant in the UBASH3A gene and its exact role
      in the pathogenesis of AD.

PMID- 28747737
TI  - Open source software for automatic detection of cone photoreceptors in adaptive
      optics ophthalmoscopy using convolutional neural networks.
AB  - Imaging with an adaptive optics scanning light ophthalmoscope (AOSLO) enables
      direct visualization of the cone photoreceptor mosaic in the living human retina.
      Quantitative analysis of AOSLO images typically requires manual grading, which is
      time consuming, and subjective; thus, automated algorithms are highly desirable.
      Previously developed automated methods are often reliant on ad hoc rules that may
      not be transferable between different imaging modalities or retinal locations. In
      this work, we present a convolutional neural network (CNN) based method for cone
      detection that learns features of interest directly from training data. This cone
      identifying algorithm was trained and validated on separate data sets of confocal
      and split detector AOSLO images with results showing performance that closely
      mimics the gold standard manual process. Further, without any need for
      algorithmic modifications for a specific AOSLO imaging system, our fully
      automated multi-modality CNN-based cone detection method resulted in comparable
      results to previous automatic cone segmentation methods which utilized ad hoc
      rules for different applications. We have made free open-source software for the
      proposed method and the corresponding training and testing datasets available
      online.

PMID- 28747738
TI  - Small fire refugia in the grassy matrix and the persistence of Afrotemperate
      forest in the Drakensberg mountains.
AB  - Afrotemperate forests situated in the Drakensberg mountains of South Africa are
      characteristically small (1-10 s ha) and widely dispersed in a vast fire-prone
      grassland. Compared with lowland forests, they are typically species poor with
      low levels of endemism and species turnover, patterns that are to date
      unexplained. Here we show that the richness, composition and functional traits of
      tree species distributed on extremely small (10-100 s m2) rocky fire-refugia
      situated in grassland are indistinguishable from that in forest. Afrotemperate
      forest tree species in the Drakensberg are widely dispersed and conform to the
      habitat generalist strategy. Most forest trees are bird dispersed; wind dispersal
      is rare and is associated only with species that resprout in response to fire. We
      present the 'matrix refuge hypothesis', which proposes that fire and extreme
      conditions associated with exposed rocky outcrops have filtered the Afrotemperate
      forest tree composition resulting in convergence in functional traits essential
      for trees to arrive, establish and persist on fire refugia in the grassland
      matrix. Most Afrotemperate forest tree diversity in the Drakensberg thus resides
      in the matrix where it may function as a recolonisation reservoir during climatic
      bottlenecks.

PMID- 28747739
TI  - Spin pump and probe in lanthanum strontium manganite/platinum bilayers.
AB  - Ferromagnetic resonance driven spin pumping (FMR-SP) is a novel method to
      transfer spin current from the ferromagnetic (FM) layer into the adjacent normal
      metal (NM) layer in an FM/NM bilayer system. Consequently, the spin current could
      be probed in NM layer via inverse spin Hall effect (ISHE). In spite of numerous
      ISHE studies on FM/Pt bilayers, La0.7Sr0.3MnO3(LSMO)/Pt system has been less
      explored and its relevant information about interface property (characterized by
      spin mixing conductance) and spin-charge conversion efficiency (characterized by
      spin Hall angle) is a matter of importance for the possible applications of
      spintronic devices. In this work, the technique of FMR-SP has been applied on two
      series of LSMO/Pt bilayers with the thickness of each layer being varied. The
      thickness dependences of ISHE voltage allow to extract the values of spin mixing
      conductance and spin Hall angle of LSMO/Pt bilayers, which are (1.8 +/- 0.4) *
      1019 m-2 and (1.2 +/- 0.1) % respectively. In comparison with other FM/Pt
      systems, LSMO/Pt has comparable spin current density and spin mixing conductance,
      regardless its distinct electronic structure from other ferromagnetic metals.

PMID- 28747740
TI  - Effects of Ni doping on various properties of NbH phases: A first-principles
      investigation.
AB  - Changes in the stability, hydrogen diffusion, and mechanical properties of the
      NbH phases from Ni-doping was studied by using first-principles methods. The
      calculation results reveal that the single H atom adsorption is energetically
      favorable at the tetrahedral interstitial site (TIS) and octahedral interstitial
      site (OIS). The preferred path of H diffusion is TIS-to-TIS, followed by TIS-to
      OIS in both Nb16H and Nb15NiH. Ni-doping in the Nb15NiH alloy lowers the energy
      barrier of H diffusion, enhances the H-diffusion coefficient (D) and mechanical
      properties of the Nb16H phase. The value of D increases with increasing
      temperature, and this trend due to Ni doping clearly becomes weaker at higher
      temperatures. At the typical operating temperature of 400 K, the D value of
      Nb15NiH (TIS) is about 1.90 * 10-8 m2/s, which is about 80 times higher than that
      of Nb16H (TIS) (2.15 * 10-10 m2/s). Our calculations indicated that Ni-doping can
      greatly improve the diffusion of H in Nb.

PMID- 28747741
TI  - The Microdamage and Expression of Sclerostin in Peri-implant Bone under One-time
      Shock Force Generated by Impact.
AB  - Osseointegration is the key to implant stability and occlusal support.
      Biomechanical response and remodeling of peri-implant bone occurs under impact
      loading. Sclerostin participates in bone formation and resorption through Wnt and
      RANKL pathways. However the mechanism of microdamage and expression of sclerostin
      in peri-implant bone under impact load is still unclear. In present study,
      specific impact forces were applied to the implants with favorable
      osseointegration in rabbits. The microdamage of peri-implant bone and the
      expression of sclerostin, beta-catenin and RANKL during the process of bone
      damage and remodeling were investigated by micro-CT, histology,
      immunofluorescence and RT-qPCR analysis. Interface separation and trabecular
      fracture were found histologically, which were consistent with micro-CT analyses.
      Throughout remodeling, bone resorption was observed during the first 14 days
      after impact, and osseointegration and normal trabecular structure were found by
      28 d. The expression of sclerostin and RANKL increased after impact and reached a
      maximum by 14 d, then decreased gradually to normal levels by 28 d. And beta
      catenin expression was opposite. Results indicated that sclerostin may involve in
      the peri-implant bone damage caused by impact and remodeling through Wnt/beta
      catenin and RANKL/RANK pathways. It will provide a new insight in the diagnosis
      and treatment for patients suffering impact.

PMID- 28747742
TI  - Mid-infrared femtosecond laser-induced damages in As2S3 and As2Se3 chalcogenide
      glasses.
AB  - In this paper, we report the first measurements of mid-infrared (MIR) femtosecond
      laser-induced damage in two typical chalcogenide glasses, As2S3 and As2Se3.
      Damage mechanism is studied via optical microscopy, scanning electron microscopy
      and elemental analysis. By irradiating at 3, 4 and 5 MUm with 150 fs ultrashort
      pulses, the evolution of crater features is presented with increasing laser
      fluence. The dependence of laser damage on the bandgap and wavelength is
      investigated and finally the laser-induced damage thresholds (LIDTs) of As2S3 and
      As2Se3 at 3 and 4 MUm are calculated from the experimental data. The results may
      be a useful for chalcogenide glasses (ChGs) applied in large laser instruments to
      prevent optical damage.

PMID- 28747743
TI  - Food Protective Effects of 3-Methylbenzaldehyde Derived from Myosotis arvensis
      and Its Analogues against Tyrophagus putrescentiae.
AB  - The potential abilities of 3-methylbenzaldehyde derived from Myosotis arvensis
      oil and its structural analogues to act as new acaricide and mite kit (mite color
      deformation) against Tyrophagus putrescentiae (Schrank) were evaluated in the
      present study. Based on the LD50 values, 2,4,5-trimethylbenzaldehyde (0.78
      MUg/cm3) had highest vapor action against T. putrescentiae, followed by 2,4
      methylbenzaldehyde (1.14 MUg/cm3), 2,5-dimethylbenzaldehyde (1.29 MUg/cm3), 2
      methylbenzaldehyde (1.32 MUg/cm3), 2,3-dimethylbenzaldehyde (1.55 MUg/cm3), 3
      methylbenzaldehyde (1.97 MUg/cm3), and 4-methylbenzaldehyde (2.34 MUg/cm3). The
      color deformation of seven methylbenzaldehyde analogues mixed with 2,3
      dihydroxybenzaldehyde against T. putrescentiae showed mite color deformation,
      from coloress to reddish brown, and valuable to distinguish with the naked eye.
      In addition, there was no antagonistic interactions between 2,3
      dihydroxybenzaldehyde and the methylbenzaldehyde analogues. These finding
      suggests that the methylbenzaldehyde analogues could be developed as dual
      functional agent to protect from fall in the commercial value of stored food
      products.

PMID- 28747744
TI  - Predicting trend of early childhood caries in mainland China: a combined meta
      analytic and mathematical modelling approach based on epidemiological surveys.
AB  - Early childhood caries (ECC) is the most common chronic disease in young
      children. A reliable predictive model for ECC prevalence is needed in China as a
      decision supportive tool for planning health resources. In this study, we first
      established the autoregressive integrated moving average (ARIMA) model and grey
      predictive model (GM) based on the estimated national prevalence of ECC with meta
      analysis from the published articles. The pooled data from 1988 to 2010 were used
      to establish the model, while the data from 2011 to 2013 were used to validate
      the models. The fitting and prediction accuracy of the two models were evaluated
      by mean absolute error (MAE) and mean absolute percentage error (MAPE). Then, we
      forecasted the annual prevalence from 2014 to 2018, which was 55.8%, 53.5%,
      54.0%, 52.9%, 51.2% by ARIMA model and 52.8%, 52.0%, 51.2%, 50.4%, 49.6% by GM.
      The declining trend in ECC prevalence may be attributed to the socioeconomic
      developments and improved public health service in China. In conclusion, both
      ARIMA and GM models can be well applied to forecast and analyze the trend of ECC;
      the fitting and testing errors generated by the ARIMA model were lower than those
      obtained from GM.

PMID- 28747745
TI  - Towards water-free biobanks: long-term dry-preservation at room temperature of
      desiccation-sensitive enzyme luciferase in air-dried insect cells.
AB  - Desiccation-tolerant cultured cells Pv11 derived from the anhydrobiotic midge
      embryo endure complete desiccation in an ametabolic state and resume their
      metabolism after rehydration. These features led us to develop a novel dry
      preservation technology for enzymes as it was still unclear whether Pv11 cells
      could preserve an exogenous enzyme in the dry state. This study shows that Pv11
      cells protect an exogenous desiccation-sensitive enzyme, luciferase (Luc),
      preserving the enzymatic activity even after dry storage for 372 days at room
      temperature. A process including preincubation with trehalose, dehydration,
      storage, and rehydration allowed Pv11 (Pv11-Luc) cells stably expressing
      luciferase to survive desiccation and still emit luminescence caused by
      luciferase after rehydration. Luminescence produced by luciferase in Pv11-Luc
      cells after rehydration did not significantly decrease in presence of a
      translation inhibitor, showing that the activity did not derive from de novo
      enzyme synthesis following the resumption of cell metabolism. These findings
      indicate that the surviving Pv11 cells almost completely protect luciferase
      during desiccation. Lacking of the preincubation step resulted in the loss of
      luciferase activity after rehydration. We showed that preincubation with
      trehalose associated to induction of desiccation tolerance-related genes in Pv11
      cells allowed effective in vivo preservation of enzymes in the dry state.

PMID- 28747746
TI  - One-step purification and immobilization of extracellularly expressed sortase A
      by magnetic particles to develop a robust and recyclable biocatalyst.
AB  - Sortase A (SrtA) is a transpeptidase widely used to site-specifically modify
      peptides and proteins and shows promise for industrial applications. In this
      study, a novel strategy was developed for constructing immobilized-SrtA as a
      robust and recyclable enzyme via direct immobilization of extracellularly
      expressed SrtA in the fermentation supernatant using magnetic particles.
      Efficient extracellular SrtA expression was achieved in Escherichia coli through
      molecular engineering, including manipulation of the protein transport pathway,
      codon optimization, and co-expression of molecular chaperones to promote
      expressed SrtA secretion into the medium at high levels. Subsequently, a simple
      one-step protocol was established for the purification and immobilization of SrtA
      containing a His-tag from the fermentation supernatant onto a nickel-modified
      magnetic particle. The immobilized SrtA was proved to retain full enzymatic
      activity for peptide-to-peptide ligation and protein modification, and was
      successfully reused for five cycles without obvious activity loss.

PMID- 28747747
TI  - Involvement of Monocyte Subsets in the Immunopathology of Giant Cell Arteritis.
AB  - Monocytes/macrophages are critical in systemic and local inflammation in giant
      cell arteritis (GCA) and possibly in clinically overlapping polymyalgia
      rheumatica (PMR). Therefore, we aimed to understand the contribution of monocyte
      subsets and the CX3CR1-CX3CL1 and CCR2-CCL2 migratory pathways, to the pathology
      of GCA. Peripheral blood monocytes were enumerated in samples from newly
      diagnosed, untreated GCA and PMR patients and after prednisone-induced remission.
      The distribution of classical (CD14brightCD16neg) and the more pro-inflammatory,
      intermediate (CD14brightCD16+) and non-classical (CD14dimCD16+) monocyte subsets
      was analysed by flow cytometry. The phenotype of macrophages in temporal artery
      biopsies (TABs) from GCA patients was studied by immunohistochemistry and
      immunofluorescence. A clear monocytosis was seen in newly diagnosed GCA and PMR
      patients caused by elevated numbers of classical monocytes. Prednisone treatment
      suppressed numbers of non-classical monocytes. Both chemokine CX3CL1 and CCL2
      were highly expressed in the TAB. Most macrophages in the TAB of GCA patients
      expressed non-classical monocyte markers CD16 and CX3CR1 whereas co-localisation
      of CD16 with classical monocyte marker CCR2 was infrequent. In conclusion, we
      report an altered distribution of monocyte subsets in both GCA and PMR patients.
      The majority of macrophages in TABs of GCA patients were CD68 + CD16 + CX3CR1 +
      CCR2- and thereby resembled the phenotype of non-classical monocytes.

PMID- 28747748
TI  - The Epigenetic Landscape of Promoter Genome-wide Analysis in Breast Cancer.
AB  - Breast cancer is a heterogeneous disease due to its clinico-pathological features
      and response to therapy. The classification of breast tumors based on their
      hormone receptor status and pathologic features. Post-translational histone
      modifications come into prominence for regulation of gene expression in cancer
      pathogenesis. Here, we analyzed dysregulation of H3K9ac and H3K27me3-enriched
      subtype-specific genes using ChIP-on-chip assay in breast cancer tumors and
      matched normal tissue samples. Breast cancer tumors were classified according to
      St Gallen Consensus 2013. Our results indicated that the promoter regions of
      genes modified by H3K9ac epi-mark are commonly associated with tumors with HER2
      positive and TNBC subtype. H3K27me3-enriched genes were comprised of Luminal A
      and B1 subtypes. We constructed a network structure to elicit epigenetically
      regulated genes related with breast cancer progression. The central genes of the
      network (RUNX1, PAX3, GATA4 and DLX5) were subjected for epigenetically
      dysregulation in association with different breast cancer subtypes. Our study
      submits epigenetic mechanisms are crucial to elicit subtype-specific regulation
      in breast cancer and ChIP-on-chip assay provides a better understanding for
      breast tumorigenesis and new approaches for prevention and treatment.

PMID- 28747749
TI  - Necessary complexity.

PMID- 28747750
TI  - The osteoarthritis and height GDF5 locus yields its secrets.
AB  - A new study reports molecular characterization of the GDF5 locus, which is
      associated with osteoarthritis risk and adult height in humans. This study
      provides evidence of positive selection for short stature at GDF5 in modern
      humans, as well as in archaic Neandertals and Denisovans.

PMID- 28747751
TI  - Monogenic immune disorders and severe atopic disease.
AB  - Severe allergic disease is common, and few monogenic causes of atopy have been
      described. A new study that convincingly links severe atopic dermatitis to
      heterozygous CARD11 mutations with dominant-interfering activity serves as a
      timely reminder that clinicians should consider the possibility of an underlying
      monogenic immune disorder when caring for patients suffering from severe allergic
      disease.

PMID- 28747753
TI  - Corrigendum: Protein-structure-guided discovery of functional mutations across 19
      cancer types.

PMID- 28747752
TI  - Erratum: Large-scale analyses of common and rare variants identify 12 new loci
      associated with atrial fibrillation.

PMID- 28747754
TI  - Corrigendum: Whole-genome sequencing identifies rare genotypes in COMP and CHADL
      associated with high risk of hip osteoarthritis.

PMID- 28747755
TI  - Hacking DNA copy number for circuit engineering.
AB  - DNA copy number represents an essential parameter in the dynamics of synthetic
      gene circuits but typically is not explicitly considered. A new study
      demonstrates how dynamic control of DNA copy number can serve as an effective
      strategy to program robust oscillations in gene expression circuits.

PMID- 28747756
TI  - Combinatorial Extracellular Matrix Microenvironments for Probing Endothelial
      Differentiation of Human Pluripotent Stem Cells.
AB  - Endothelial cells derived from human pluripotent stem cells are a promising cell
      type for enhancing angiogenesis in ischemic cardiovascular tissues. However, our
      understanding of microenvironmental factors that modulate the process of
      endothelial differentiation is limited. We examined the role of combinatorial
      extracellular matrix (ECM) proteins on endothelial differentiation systematically
      using an arrayed microscale platform. Human pluripotent stem cells were
      differentiated on the arrayed ECM microenvironments for 5 days. Combinatorial
      ECMs composed of collagen IV + heparan sulfate + laminin (CHL) or collagen IV +
      gelatin + heparan sulfate (CGH) demonstrated significantly higher expression of
      CD31, compared to single-factor ECMs. These results were corroborated by
      fluorescence activated cell sorting showing a 48% yield of CD31+/VE-cadherin+
      cells on CHL, compared to 27% on matrigel. To elucidate the signaling mechanism,
      a gene expression time course revealed that VE-cadherin and FLK1 were upregulated
      in a dynamically similar manner as integrin subunit beta3 (>50 fold). To
      demonstrate the functional importance of integrin beta3 in promoting endothelial
      differentiation, the addition of neutralization antibody inhibited endothelial
      differentiation on CHL-modified dishes by >50%. These data suggest that optimal
      combinatorial ECMs enhance endothelial differentiation, compared to many single
      factor ECMs, in part through an integrin beta3-mediated pathway.

PMID- 28747757
TI  - TGFbeta-induced osteogenic potential of human amniotic fluid stem cells via CD73
      generated adenosine production.
AB  - The human amniotic fluid stem cell (hAFSC) population consists of two
      morphologically distinct subtypes, spindle-shaped and round-shaped cells (SS
      hAFSCs and RS-hAFSCs). Whilst SS-hAFSCs are routinely expanded in mesenchymal
      type (MT) conditions, we previously showed that they acquire broader
      differentiation potential when cultured under embryonic-type (ET) conditions.
      However, the effects of culture conditions on RS-hAFSCs have not been determined.
      Here, we show that culturing RS-hAFSCs under ET conditions confers faster
      proliferation and enhances the efficiency of osteogenic differentiation of the
      cells. We show that this occurs via TGFbeta-induced activation of CD73 and the
      associated increase in the generation of extracellular adenosine. Our data
      demonstrate that culture conditions are decisive for the expansion of hAFSCs and
      that TGFbeta present in ET conditions causes the phenotype of RS-hAFSCs to revert
      to an earlier state of stemness. Cultivating RS-hAFSCs in ET conditions with
      TGFbeta may therefore increase their therapeutic potential for clinical
      applications.

PMID- 28747758
TI  - How vegetation in flows modifies the turbulent mixing and spreading of jets.
AB  - While studies on vegetated channel flows have been developed in many research
      centers, studies on jets interacting with vegetation are still rare. This study
      presents and analyzes turbulent jets issued into an obstructed cross-flow, with
      emergent vegetation simulated with a regular array of cylinders. The paper
      presents estimates of the turbulence diffusion coefficients and the main
      turbulence variables of jets issued into a vegetated channel flow. The
      experimental results are compared with jets issued into unobstructed cross-flow.
      In the presence of the cylinder array, the turbulence length-scales in the
      streamwise and transverse directions were reduced, relative to the unobstructed
      crossflow. This contributed to a reduction in streamwise turbulent diffusion,
      relative to the unobstructed conditions. In contrast, the transverse turbulent
      diffusion was enhanced, despite the reduction in length-scale, due to enhanced
      turbulent intensity and the transverse deflection of flow around individual
      cylinders. Importantly, in the obstructed condition, the streamwise and
      transverse turbulent diffusion coefficients are of the same order of magnitude.

PMID- 28747759
TI  - Slow conformational exchange and overall rocking motion in ubiquitin protein
      crystals.
AB  - Proteins perform their functions in solution but their structures are most
      frequently studied inside crystals. Here we probe how the crystal packing alters
      microsecond dynamics, using solid-state NMR measurements and multi-microsecond MD
      simulations of different crystal forms of ubiquitin. In particular, near-rotary
      resonance relaxation dispersion (NERRD) experiments probe angular backbone
      motion, while Bloch-McConnell relaxation dispersion data report on fluctuations
      of the local electronic environment. These experiments and simulations reveal
      that the packing of the protein can significantly alter the thermodynamics and
      kinetics of local conformational exchange. Moreover, we report small-amplitude
      reorientational motion of protein molecules in the crystal lattice with an ~3-5
      degrees  amplitude on a tens-of-microseconds time scale in one of the crystals,
      but not in others. An intriguing possibility arises that overall motion is to
      some extent coupled to local dynamics. Our study highlights the importance of
      considering the packing when analyzing dynamics of crystalline proteins.X-ray
      crystallography is the main method for protein structure determination. Here the
      authors combine solid-state NMR measurements and molecular dynamics simulations
      and show that crystal packing alters the thermodynamics and kinetics of local
      conformational exchange as well as overall rocking motion of protein molecules in
      the crystal lattice.

PMID- 28747760
TI  - Early functional network alterations in asymptomatic elders at risk for
      Alzheimer's disease.
AB  - Amyloid-beta (Abeta) deposition is known to starts decades before the onset of
      clinical symptoms of Alzheimer's disease (AD), however, the detailed
      pathophysiological processes underlying this preclinical period are not well
      understood. This study aimed to investigate functional network alterations in
      cognitively intact elderly individuals at risk for AD, and assessed the
      association between these network alterations and changes in Abeta deposition,
      glucose metabolism, and brain structure. Forty-five cognitively normal elderly
      subjects, who were classified into Abeta-positive (CN+) and Abeta-negative (CN-)
      groups using 11C-Pittsburgh compound B PET, underwent resting state
      magnetoencephalography measurements, 18F-fluorodeoxyglucose PET (FDG-PET) and
      structural MRI. Results demonstrated that in the CN+ group, functional
      connectivity (FC) within the precuneus was significantly decreased, whereas it
      was significantly enhanced between the precuneus and the bilateral inferior
      parietal lobules in the low-frequency bands (theta and delta). These changes were
      suggested to be associated with local cerebral Abeta deposition. Most of Abeta+
      individuals in this study did not show any metabolic or anatomical changes, and
      there were no significant correlations between FC values and FDG-PET or MRI
      volumetry data. These results demonstrate that functional network alterations,
      which occur in association with Abeta deposition, are detectable using
      magnetoencephalography before metabolic and anatomical changes are seen.

PMID- 28747761
TI  - BMP2-modified injectable hydrogel for osteogenic differentiation of human
      periodontal ligament stem cells.
AB  - This is the first report on the development of a covalently bone morphogenetic
      protein-2 (BMP2)-immobilized hydrogel that is suitable for osteogenic
      differentiation of human periodontal ligament stem cells (hPLSCs). O-propargyl
      tyrosine (OpgY) was site-specifically incorporated into BMP2 to prepare BMP2-OpgY
      with an alkyne group. The engineered BMP2-OpgY exhibited osteogenic
      characteristics after in vitro osteogenic differentiation of hPLSCs, indicating
      the osteogenic ability of BMP2-OpgY. A methoxy polyethylene glycol
      (polycaprolactone-(N3)) block copolymer (MC-N3) was prepared as an injectable in
      situ-forming hydrogel. BMP2 covalently immobilized on an MC hydrogel (MC-BMP2)
      was prepared quantitatively by a simple biorthogonal reaction between alkyne
      groups on BMP2-OpgY and azide groups on MC-N3 via a Cu(I)-catalyzed click
      reaction. The hPLSCs-loaded MC-BMP2 formed a hydrogel almost immediately upon
      injection into animals. In vivo osteogenic differentiation of hPLSCs in the MC
      BMP2 formulation was confirmed by histological staining and gene expression
      analyses. Histological staining of hPLSC-loaded MC-BMP2 implants showed evidence
      of mineralized calcium deposits, whereas hPLSC-loaded MC-Cl or BMP2-OpgY mixed
      with MC-Cl, implants showed no mineral deposits. Additionally, MC-BMP2 induced
      higher levels of osteogenic gene expression in hPLSCs than in other groups. In
      conclusion, BMP2-OpgY covalently immobilized on MC-BMP2 induced osteogenic
      differentiation of hPLSCs as a noninvasive method for bone tissue engineering.

PMID- 28747762
TI  - Molecular mechanisms of Charcot-Marie-Tooth neuropathy linked to mutations in
      human myelin protein P2.
AB  - Charcot-Marie-Tooth (CMT) disease is one of the most common inherited
      neuropathies. Recently, three CMT1-associated point mutations (I43N, T51P, and
      I52T) were discovered in the abundant peripheral myelin protein P2. These
      mutations trigger abnormal myelin structure, leading to reduced nerve conduction
      velocity, muscle weakness, and distal limb atrophy. P2 is a myelin-specific
      protein expressed by Schwann cells that binds to fatty acids and membranes,
      contributing to peripheral myelin lipid homeostasis. We studied the molecular
      basis of the P2 patient mutations. None of the CMT1-associated mutations alter
      the overall folding of P2 in the crystal state. P2 disease variants show
      increased aggregation tendency and remarkably reduced stability, T51P being most
      severe. In addition, P2 disease mutations affect protein dynamics. Both fatty
      acid binding by P2 and the kinetics of its membrane interactions are affected by
      the mutations. Experiments and simulations suggest opening of the beta barrel in
      T51P, possibly representing a general mechanism in fatty acid-binding proteins.
      Our findings demonstrate that altered biophysical properties and functional
      dynamics of P2 may cause myelin defects in CMT1 patients. At the molecular level,
      a few malformed hydrogen bonds lead to structural instability and misregulation
      of conformational changes related to ligand exchange and membrane binding.

PMID- 28747763
TI  - Efficacy and Safety of Very Early Mobilization in Patients with Acute Stroke: A
      Systematic Review and Meta-analysis.
AB  - Whether very early mobilization (VEM) improves outcomes in stroke patients and
      reduces immobilization-related complications (IRCs) is currently unknown. The
      objective of this systematic review and meta-analysis was to evaluate the
      efficacy and safety of VEM in acute stroke patients following admission. Medline,
      Embase, and Cochrane Central Register of Controlled Trials databases were
      searched for randomized controlled trials (RCTs) that examined the efficacy or
      safety of VEM in patients with acute stroke. VEM was defined as out of bed
      activity commencing within 24 or 48 hours after the onset of stroke. A total of 9
      RCTs with 2,803 participants were included. Upon analysis, VEM was not associated
      with favorable functional outcomes (modified Ranking Scale: 0-2) at 3 months
      [relative risk (RR): 0.96; 95% confidence interval (CI): 0.86-1.06]; VEM did not
      reduce the risk of IRCs during follow up. With respect to safety outcomes, VEM
      was not associated with a higher risk of death (RR: 1.04; 95% CI: 0.52-2.09) and
      did not increase the risk of neurological deterioration or incidence of falls
      with injury. In conclusion, pooled data from RCTs concluded that VEM is not
      associated with beneficial effects when carried out in patients 24 or 48 hours
      after the onset of a stroke.

PMID- 28747764
TI  - Super-strong dislocation-structured high-carbon martensite steel.
AB  - High-carbon martensite steels (with C > 0.5 wt.%) are very hard but at the same
      time as brittle as glass in as-quenched or low-temperature-tempered state. Such
      extreme brittleness, originating from a twin microstructure, has rendered these
      steels almost useless in martensite state. Therefore, for more than a century it
      has been a common knowledge that high-carbon martensitic steels are intrinsically
      brittle and thus are not expected to find any application in harsh loading
      conditions. Here we report that these brittle steels can be transformed into
      super-strong ones exhibiting a combination of ultrahigh strength and significant
      toughness, through a simple grain-refinement treatment, which refines the grain
      size to ~4 MUm. As a result, an ultra-high tensile strength of 2.4~2.6 GPa, a
      significant elongation of 4~10% and a good fracture toughness (K1C) of 23.5~29.6
      MPa m1/2 were obtained in high-carbon martensitic steels with 0.61-0.65 wt.% C.
      These properties are comparable with those of "the king of super-high-strength
      steels"-maraging steels, but achieved at merely 1/30~1/50 of the price. The
      drastic enhancement in mechanical properties is found to arise from a transition
      from the conventional twin microstructure to a dislocation one by grain
      refinement. Our finding may provide a new route to manufacturing super-strong
      steels in a simple and economic way.

PMID- 28747765
TI  - Troponin I and T in relation to cardiac injury detected with electrocardiography
      in a population-based cohort - The Maastricht Study.
AB  - Interest in high-sensitivity cardiac troponin I(hs-cTnI) and T(hs-cTnT) has
      expanded from acute cardiac care to cardiovascular disease(CVD) risk
      stratification. Whether hs-cTnI and hs-cTnT are interchangeable in the ambulant
      setting is largely unexplored. Cardiac injury is a mechanism that may underlie
      the associations between troponin levels and mortality in the general population.
      In the population-based Maastricht Study, we assessed the correlation and
      concordance between hs-cTnI and hs-cTnT. Multiple regression analyses were
      conducted to assess the association of hs-cTnI and hs-cTnT with
      electrocardiographic (ECG) changes indicative of cardiac abnormalities. In 3016
      eligible individuals(mean age,60 +/- 8years;50.6%,men) we found a modest
      correlation between hs-cTnI and hs-cTnT(r = 0.585). After multiple adjustment,
      the association with ECG changes indicative of cardiac abnormalities was similar
      for both hs-cTn assays(OR,hs-cTnI:1.72,95%CI:1.40-2.10;OR,hs-cTnT:1.60,95%CI:1.22
      2.11). The concordance of dichotomized hs-cTnI and hs-cTnT was kappa =
      0.397(>=sex-specific 75th percentile). Isolated high levels of hs-cTnI were
      associated with ECG changes indicative of cardiac
      abnormalities(OR:1.93,95%CI:1.01-3.68), whereas isolated high levels of hs-cTnT
      were not(OR:1.07,95%CI:0.49-2.31). In conclusion, there is a moderate correlation
      and limited concordance between hs-cTnI and hs-cTnT under non-acute conditions.
      These data suggest that associations of hs-cTnI and hs-cTnT with cardiac injury
      detected by ECG are driven by different mechanisms. This information may benefit
      future development of CVD risk stratification algorithms.

PMID- 28747766
TI  - DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells
      of patients undergoing alcohol treatment.
AB  - Several studies have shown an association of alcohol dependence with DNA
      methylation (DNAm), suggesting that environmentally-induced changes on epigenomic
      variation may play an important role in alcohol dependence. In the present study,
      we analysed genome-wide DNAm profiles of purified CD3+ T-cells from pre- and post
      treatment alcohol dependent patients, as well as closely matched healthy
      controls. We identified 59 differentially methylated CpG sites comparing patients
      prior to treatment with healthy controls and were able to confirm 8 of those
      sites in additional analyses for differentially methylated regions. Comparing
      patients before and after a 3-week alcohol treatment program we revealed another
      unique set of 48 differentially methylated CpG sites. Additionally, we found that
      the mean global DNAm was significantly lower in patients prior to treatment
      compared to controls, but reverted back to levels similar to controls after
      treatment. We validated top-ranked hits derived from the epigenome-wide analysis
      by pyrosequencing and further replicated two of them in an independent cohort and
      confirmed differential DNAm of HECW2 and SRPK3 in whole blood. This study is the
      first to show widespread DNAm variation in a disease-relevant blood cell type and
      implicates HECW2 and SRPK3 DNAm as promising blood-based candidates to follow up
      in future studies.

PMID- 28747767
TI  - Quality assessment of Chinese liquor with different ages and prediction analysis
      based on gas chromatography and electronic nose.
AB  - The economic value of Chinese liquor is closely related with its age. Results
      from gas chromatograph (GC) analysis indicated that 8 dominant compounds were
      decreased with the increase of liquor age (0 to 5 years) while ethyl lactate was
      found to be the most stable dominant compound as no significant change was
      observed in it during the aging process. Liquor groups with different ages were
      well-discriminated by principal component analysis (PCA) based on electronic nose
      signals. High-accurate identification of liquor ages was realized using linear
      discriminant analysis (LDA) with the accuracy of 98.3% of the total 120 samples
      from six age groups. Partial least squares regression (PLSR) exhibited satisfying
      ability for liquor age prediction (R2: 0.9732 in calibration set and 0.9101 in
      validation set). The feasibility of volatile compounds prediction using PLSR
      combined with electronic nose was also verified by this research. However, the
      accuracies of PLSR models can be further promoted in future researches, perhaps
      by using more suitable sensors or modeling approaches.

PMID- 28747768
TI  - Controlling Adult Stem Cell Behavior Using Nanodiamond-Reinforced Hydrogel:
      Implication in Bone Regeneration Therapy.
AB  - Nanodiamonds (NDs) have attracted considerable attention as drug delivery
      nanocarriers due to their low cytotoxicity and facile surface functionalization.
      Given these features, NDs have been recently investigated for the fabrication of
      nanocomposite hydrogels for tissue engineering. Here we report the synthesis of a
      hydrogel using photocrosslinkable gelatin methacrylamide (GelMA) and NDs as a
      three-dimensional scaffold for drug delivery and stem cell-guided bone
      regeneration. We investigated the effect of different concentration of NDs on the
      physical and mechanical properties of the GelMA hydrogel network. The inclusion
      of NDs increased the network stiffness, which in turn augmented the traction
      forces generated by human adipose stem cells (hASCs). We also tested the ability
      of NDs to adsorb and modulate the release of a model drug dexamethasone (Dex) to
      promote the osteogenic differentiation of hASCs. The ND-Dex complexes modulated
      gene expression, cell area, and focal adhesion number in hASCs. Moreover, the
      integration of the ND-Dex complex within GelMA hydrogels allowed a higher
      retention of Dex over time, resulting in significantly increased alkaline
      phosphatase activity and calcium deposition of encapsulated hASCs. These results
      suggest that conventional GelMA hydrogels can be coupled with conjugated NDs to
      develop a novel platform for bone tissue engineering.

PMID- 28747769
TI  - Response of cotton phenology to climate change on the North China Plain from 1981
      to 2012.
AB  - To identify countermeasures for the impacts of climate change on crop production,
      exploring the changes in crop phenology and their relationship to climate change
      is required. This study was based on cotton phenology and climate data collected
      from 13 agro-meteorological experimental stations and 13 meteorological stations
      on the North China Plain from 1981 to 2012. Spatiotemporal trends in the cotton
      phenology data, lengths of the different growing phases, mean temperatures, and
      rainfall were analyzed. These results indicated that warming accelerated cotton
      growth, advanced cotton phenology, and shortened the growing period of cotton.
      However, harvest dates were significantly delayed at 8 (61.5%) stations, the
      length of both the flowering-boll opening and boll opening-harvest periods
      increased at 10 (77.0%) stations, and a positive correlation was found between
      the mean temperature and the length of the whole growing period at 10 (77.0%)
      stations. Therefore, cotton practices and cultivars on the North China Plain
      should be adjusted accordingly. The response of cotton phenology to climate
      change, as shown here, can further guide the development of options for the
      adaptation of cotton production in the near future.

PMID- 28747770
TI  - The Distribution Characteristics and Applications for Maternal Cells on Chicken
      Egg Vitelline Membrane.
AB  - The major components of vitelline membrane (VM) are ovomucin, VM outer (VMO) I
      and VMO II. At present, the distribution pattern of maternal cells on the VM has
      not been described in detail. In this study, the existence and distribution
      characteristics of maternal cells on VM were observed. There were more than 3.2 *
      105 somatic cells on VM, which were uneven distributed. The calcein AM/PI
      staining of the maternal cells on the VM showed that the cells' viability changed
      with the freshness of the eggs, and that the maternal cells gradually underwent
      apoptosis and became degraded. The results of morphology of different tissues
      indicated that the most of maternal cells on the VM were granulosa cells.
      Moreover, the karyotype of the cultured granulosa cells, which is the main source
      of cells on VM, were identified as the normal diploid karyotype of chicken.
      Furthermore, the VM DNA extracted from chickens and quails, which represent the
      eggs of different size, was adequate for further genetic analysis. The VM DNA was
      easily accessible and relatively constant, without cross-contamination.
      Therefore, the VM DNA could potentially be applied for the molecular traceability
      between eggs and chickens, and be beneficial in avian ecology research studies.

PMID- 28747771
TI  - Different Potential of Extracellular Vesicles to Support Thrombin Generation:
      Contributions of Phosphatidylserine, Tissue Factor, and Cellular Origin.
AB  - Cells release diverse types of vesicles constitutively or in response to
      proliferation, injury, inflammation, or stress. Extracellular vesicles (EVs) are
      crucial in intercellular communication, and there is emerging evidence for their
      roles in inflammation, cancer, and thrombosis. We investigated the
      thrombogenicity of platelet-derived EVs, which constitute the majority of
      circulating EVs in human blood, and assessed the contributions of
      phosphatidylserine and tissue factor exposure on thrombin generation. Addition of
      platelet EVs to vesicle-free human plasma induced thrombin generation in a dose
      dependent manner, which was efficiently inhibited by annexin V, but not by anti
      tissue factor antibodies, indicating that it was primarily due to the exposure of
      phosphatidylserine on platelet EVs. Platelet EVs exhibited higher thrombogenicity
      than EVs from unstimulated monocytic THP-1 cells, but blockade of contact
      activation significantly reduced thrombin generation by platelet EVs. Stimulation
      of monocytic cells with lipopolysaccharide enhanced their thrombogenicity both in
      the presence and in the absence of contact activation, and thrombin generation
      was efficiently blocked by anti-tissue factor antibodies. Our study provides
      evidence that irrespective of their cellular origin, EVs support the propagation
      of coagulation via the exposure of phosphatidylserine, while the expression of
      functional tissue factor on EVs appears to be limited to pathological conditions.

PMID- 28747773
TI  - Deciphering mechanisms of acquired T790M mutation after EGFR inhibitors for NSCLC
      by computational simulations.
AB  - Metastatic non-small-cell lung cancer (NSCLC) with activating EGFR mutations
      responds very well to first and second generation tyrosine-kinase inhibitors
      (TKI) including gefitinib, erlotinib and afatinib. Unfortunately, drug resistance
      will eventually develop and about half of the cases are secondary to the
      emergence of acquired T790M somatic mutation. In this work, we prospectively
      recruited 68 patients with metastatic EGFR-mutated NSCLC who have developed
      progressive disease after first-line TKI with or without subsequent TKI and/or
      other systemic therapy. Liquid biopsy after progression to their last line of
      systemic therapy were taken for detection of acquired T790M mutation. By
      performing attribute ranking we found that several attributes, including the
      initial EGFR mutational type, had a high correlation with the presence of
      acquired T790M mutation. We also conducted computational studies and discovered
      that the EGFR mutation delE746_A750 had a lower stability around the residue T790
      than delS752_I759 and L858R, which was consistent with our clinical observation
      that patients with delE746_A750 were more likely to acquire T790M mutation than
      those with delS752_I759 or L858R. Our results provided new insight to future
      direction of research on investigating the mechanisms of acquired T790M mutation,
      which is essential to the development of novel mutation-specific TKIs.

PMID- 28747774
TI  - A room-temperature refuelable lithium, iodine and air battery.
AB  - We demonstrate a new refuelable lithium cell using lithium solvated electron
      solution (Li-SES) as anolyte and iodine solutions as catholyte. This cell shows a
      high OCV (~3 V). Unlike conventional rechargeable Li batteries, this kind of cell
      can be re-fueled in several minutes by replacing the spent liquids. We also show
      for the first time, that Li-SES/I2 cells which operate at room temperature, can
      be prepared in a fully discharged state (~0 V OCV) for safe handling,
      transportation and storage. Li-SES and iodine are then electrochemically
      generated during charge as is confirmed by UV-VIS and a qualitative test. We have
      also conducted proof-of-concept tests for an "indirect lithium-air" cell in which
      iodine is reduced at the cathode and subsequently is catalytically re-oxidized by
      oxygen dissolved in the catholyte.

PMID- 28747775
TI  - Curcumin and Curcuma longa L. extract ameliorate lipid accumulation through the
      regulation of the endoplasmic reticulum redox and ER stress.
AB  - For this study, we examined the effects of curcumin against acute and chronic
      stress, paying specific attention to ROS. We also aimed to clarify the
      differences between acute and chronic stress conditions. We investigated the
      effects of curcumin against acute stress (once/1 day CCl4 treatment) and chronic
      stress (every other day/4week CCl4 treatment). Compared with acute stress, in
      which the antioxidant system functioned properly and aspartate transaminase (AST)
      and ROS production increased, chronic stress increased AST, alanine
      aminotransferase (ALT), hepatic enzymes, and ROS more significantly, and the
      antioxidant system became impaired. We also found that ER-originated ROS
      accumulated in the chronic model, another difference between the two conditions.
      ER stress was induced consistently, and oxidative intra-ER protein folding
      status, representatively PDI, was impaired, especially in chronic stress. The PDI
      associated client protein hepatic apoB accumulated with the PDI-binding status in
      chronic stress, and curcumin recovered the altered ER folding status, regulating
      ER stress and the resultant hepatic dyslipidemia. Throughout this study, curcumin
      and curcumin-rich Curcuma longa L. extract promoted recovery from CCl4-induced
      hepatic toxicity in both stress conditions. For both stress-associated hepatic
      dyslipidemia, curcumin and Curcuma longa L. extract might be recommendable to
      recover liver activity.

PMID- 28747777
TI  - Sleep and memory: Spindles take charge.

PMID- 28747778
TI  - Psychiatric disorders: Splitting depression apart.

PMID- 28747776
TI  - Animal models of alpha-synucleinopathy for Parkinson disease drug development.
AB  - A major challenge in Parkinson disease (PD) will be to turn an emerging and
      expanding pipeline of novel disease-modifying candidate compounds into
      therapeutics. Novel targets need in vivo validation, and candidate therapeutics
      require appropriate preclinical platforms on which to define potential efficacy
      and target engagement before advancement to clinical development. We propose that
      alpha-synuclein (alpha-syn)-based mammalian models will be crucial for this
      process. Here, we review alpha-syn transgenic mouse models, viral vector models
      of alpha-syn overexpression and models of 'prion-like' spread of alpha-syn, and
      describe how each of these model types may contribute to PD drug discovery. We
      conclude by presenting our opinion on how to use a combination of these models
      through the late-stage preclinical, proof-of-principle investigation of novel
      therapeutics.

PMID- 28747779
TI  - Fungal root symbionts of high-altitude vascular plants in the Himalayas.
AB  - Arbuscular mycorrhizal fungi (AMF) and dark septate endophytes (DSE) form
      symbiotic relationships with plants influencing their productivity, diversity and
      ecosystem functions. Only a few studies on these fungi, however, have been
      conducted in extreme elevations and none over 5500 m a.s.l., although vascular
      plants occur up to 6150 m a.s.l. in the Himalayas. We quantified AMF and DSE in
      roots of 62 plant species from contrasting habitats along an elevational gradient
      (3400-6150 m) in the Himalayas using a combination of optical microscopy and next
      generation sequencing. We linked AMF and DSE communities with host plant
      evolutionary history, ecological preferences (elevation and habitat type) and
      functional traits. We detected AMF in elevations up to 5800 m, indicating it is
      more constrained by extreme conditions than the host plants, which ascend up to
      6150 m. In contrast, DSE were found across the entire gradient up to 6150 m. AMF
      diversity was unimodally related to elevation and positively related to the
      intensity of AMF colonization. Mid-elevation steppe and alpine plants hosted more
      diverse AMF communities than plants from deserts and the subnival zone. Our
      results bring novel insights to the abiotic and biotic filters structuring AMF
      and DSE communities in the Himalayas.

PMID- 28747780
TI  - Novel strategies to mimic transmembrane tumor necrosis factor-dependent
      activation of tumor necrosis factor receptor 2.
AB  - Tumor necrosis factor receptor 2 (TNFR2) is known to mediate immune suppression
      and tissue regeneration. Interestingly, the transmembrane form of tumor necrosis
      factor (tmTNF) is necessary to robustly activate TNFR2. To characterize the
      stoichiometry and composition of tmTNF during TNFR2 activation, we constructed
      differently oligomerized single chain TNF ligands (scTNF) comprised of three TNF
      homology domain (THD) protomers that mimic tmTNF. Using a variety of cellular and
      in vivo assays, we can show that higher oligomerization of the scTNF trimers
      results in more efficient TNF/TNFR2 clustering and subsequent signal
      transduction. Importantly, the three-dimensional orientation of the scTNF trimers
      impacts the bioactivity of the oligomerized scTNF ligands. Our data unravel the
      organization of tmTNF-mimetic scTNF ligands capable of robustly activating TNFR2
      and introduce novel TNFR2 agonists that hold promise as therapeutics to treat a
      variety of diseases.

PMID- 28747781
TI  - Targeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal
      squamous cell carcinoma mouse model.
AB  - Although conventional chemoradiotherapy is effective for most anal squamous cell
      carcinoma (ASCC) patients, HPV-negative ASCC patients respond poorly to this
      treatment and new therapeutic approach is required. Our group has previously
      established an HPV-negative ASCC mouse model and demonstrated that signal
      transducer and activation of transcription 3 (STAT3) is hyper-activated in the
      model. Here, we show that in vivo inhibition of STAT3 by S3I-201 effectively
      delays tumor growth in ASCC mouse model indicated by significantly smaller tumor
      size and burden in the treatment group compared with control group at the same
      point. Further analysis shows that survivin and Ki67, important biomarkers for
      tumor cell survival and proliferation, are significantly reduced after S3I-201
      treatment. Additionally, flow cytometry and immunohistofluorescent assays reveal
      decreased Myeloid-derived suppressor cell (MDSC) and tumor-associated macrophage
      (TAM) populations in the S3I-201 treatment group, which indicates a reversion of
      the immunosuppressive environment, unraveling the potential role for S3I-201 in
      immunosuppression in ASCC. Together these results for the first time demonstrated
      the anti-tumor effects of STAT3 inhibitor S3I-201 in HPV-negative ASCC mouse
      model and its multiple effects on cancer cells and immune system. Thus we
      conclude that S3I-201 may be a novel therapeutic approach for HPV-negative ASCC
      patients.

PMID- 28747782
TI  - Hybrid High-order Functional Connectivity Networks Using Resting-state Functional
      MRI for Mild Cognitive Impairment Diagnosis.
AB  - Conventional functional connectivity (FC), referred to as low-order FC, estimates
      temporal correlation of the resting-state functional magnetic resonance imaging
      (rs-fMRI) time series between any pair of brain regions, simply ignoring the
      potentially high-level relationship among these brain regions. A high-order FC
      based on "correlation's correlation" has emerged as a new approach for
      abnormality detection of brain disease. However, separate construction of the low
      and high-order FC networks overlooks information exchange between the two FC
      levels. Such a higher-level relationship could be more important for brain
      diseases study. In this paper, we propose a novel framework, namely "hybrid high
      order FC networks" by exploiting the higher-level dynamic interaction among brain
      regions for early mild cognitive impairment (eMCI) diagnosis. For each sliding
      window-based rs-fMRI sub-series, we construct a whole-brain associated high-order
      network, by estimating the correlations between the topographical information of
      the high-order FC sub-network from one brain region and that of the low-order FC
      sub-network from another brain region. With multi-kernel learning, complementary
      features from multiple time-varying FC networks constructed at different levels
      are fused for eMCI classification. Compared with other state-of-the-art methods,
      the proposed framework achieves superior diagnosis accuracy, and hence could be
      promising for understanding pathological changes of brain connectome.

PMID- 28747783
TI  - Engineering the geometrical shape of mesenchymal stromal cells through defined
      cyclic stretch regimens.
AB  - Stem cells have been predicted to improve disease outcomes and patient lives.
      Steering stem cell fate - through controlling cell shape - may substantially
      accelerate progress towards this goal. As mesenchymal stromal cells (MSCs) are
      continuously exposed in vivo to a dynamically changing biomechanical environment,
      we hypothesized that exogenous forces can be applied for engineering a variety of
      significantly different MSC shapes. We applied specific cyclic stretch regimens
      to human MSCs and quantitatively measured the resulting cell shape, alignment,
      and expression of smooth muscle (SMC) differentiation markers, as those have been
      associated with elongated morphology. As proof of principle, a range of different
      shapes, alignments, and correlating SMC marker levels were generated by varying
      strain, length, and repetition of stretch. However, the major determinant of
      biomechanically engineering cellular shape was the repetition of a chosen stretch
      regimen, indicating that the engineered shape and associated differentiation were
      complex non-linear processes relying on sustained biomechanical stimulation.
      Thus, forces are key regulators of stem cell shape and the targeted engineering
      of specific MSC shapes through biomechanical forces represents a novel
      mechanobiology concept that could exploit naturally occurring in vivo forces for
      improving stem cell fate in clinical regenerative therapies.

PMID- 28747784
TI  - Elevated CO2 and nitrogen addition have minimal influence on the rhizospheric
      effects of Bothriochloa ischaemum.
AB  - The influence of elevated CO2 and nitrogen (N) addition on soil microbial
      communities and the rhizospheric effects of Bothriochloa ischaemum were
      investigated. A pot-cultivation experiment was conducted in climate-controlled
      chambers under two levels of CO2 (400 and 800 MUmol mol-1) and three levels of N
      addition (0, 2.5, and 5 g N m-2 y-1). Soil samples (rhizospheric and bulk soil)
      were collected for the assessment of soil organic carbon (SOC), total N (TN),
      total phosphorus (TP), basal respiration (BR), and phospholipid fatty acids
      (PLFAs) 106 days after treatments were conducted. Elevated CO2 significantly
      increased total and fungal PLFAs in the rhizosphere when combined with N
      addition, and N addition significantly increased BR in the rhizosphere and total,
      bacterial, fungal, Gram-positive (G+), and Gram-negative (G-) PLFAs in both
      rhizospheric and bulk soil. BR and total, bacterial, G+, and G+/G- PLFAs were
      significantly higher in rhizospheric than bulk soil, but neither elevated CO2 nor
      N addition affected the positive rhizospheric effects on bacterial, G+, or G+/G-
      PLFAs. N addition had a greater effect on soil microbial communities than
      elevated CO2, and elevated CO2 and N addition had minor contributions to the
      changes in the magnitude of the rhizospheric effects in B. ischaemum.

PMID- 28747785
TI  - Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K.
      pneumoniae O3.
AB  - Klebsiella pneumoniae is responsible for nosocomial infections causing
      significant morbidity and mortality. Treatment of newly emerging multi-drug
      resistant strains is hampered due to severely limited antibiotic choices. Passive
      immunization targeting LPS O-antigens has been proposed as an alternative
      therapeutic option, given the limited variability of Klebsiella O-antigens. Here
      we report that the O3 serogroup, previously considered to have uniform O-antigen
      built of mannan, represents three different subtypes differing in the number of
      mannose residues within the O-antigen repeating units. Genetic analysis of the
      genes encoding mannose polymerization revealed differences that underline the
      observed structural alterations. The O3 variants represent antigenically
      different types based on the different reactivity pattern of murine monoclonal
      antibodies raised against a K. pneumoniae O3 strain. Typing of a collection of K.
      pneumoniae O3 clinical isolates showed that strains expressing the novel O3b
      antigen, the tri-mannose form, were more prevalent than those having the penta
      mannose form, traditionally called O3, while the tetra-mannose variant, termed
      here O3a, seems to be rare. A monoclonal antibody cross-reacting with all three
      O3 sub-serogroups was also selected and shown to bind to the surface of various
      K. pneumoniae strains expressing different O3 subtypes and capsular antigens.

PMID- 28747786
TI  - Highly Efficient Photocatalytic Z-Scheme Hydrogen Production over Oxygen
      Deficient WO3-x Nanorods supported Zn0.3Cd0.7S Heterostructure.
AB  - The demand for clean renewable energy is increasing due to depleting fossil fuels
      and environmental concerns. Photocatalytic hydrogen production through water
      splitting is one such promising route to meet global energy demands with carbon
      free technology. Alternative photocatalysts avoiding noble metals are highly
      demanded. Herein, we fabricated heterostructure consist of oxygen-deficient WO3-x
      nanorods with Zn0.3Cd0.7S nanoparticles for an efficient Z-Scheme photocatalytic
      system. Our as obtained heterostructure showed photocatalytic H2 evolution rate
      of 352.1 MUmol h-1 with apparent quantum efficiency (AQY) of 7.3% at lambda = 420
      nm. The photocatalytic hydrogen production reaches up to 1746.8 MUmol after 5
      hours process in repeatable manner. The UV-Visible diffuse reflectance spectra
      show strong absorption in the visible region which greatly favors the
      photocatalytic performance. Moreover, the efficient charge separation suggested
      by electrochemical impedance spectroscopy and photocurrent response curves
      exhibit enhancement in H2 evolution rate. The strong interface contact between
      WO3-x nanorods and Zn0.3Cd0.7S nanoparticles ascertained from HRTEM images also
      play an important role for the emigration of electron. Our findings provide
      possibilities for the design and development of new Z-scheme photocatalysts for
      highly efficient hydrogen production.

PMID- 28747787
TI  - Hydro-dynamic Solute Transport under Two-Phase Flow Conditions.
AB  - There are abundant examples of natural, engineering and industrial applications,
      in which "solute transport" and "mixing" in porous media occur under multiphase
      flow conditions. Current state-of-the-art understanding and modelling of such
      processes are established based on flawed and non-representative models.
      Moreover, there is no direct experimental result to show the true hydrodynamics
      of transport and mixing under multiphase flow conditions while the saturation
      topology is being kept constant for a number of flow rates. With the use of a
      custom-made microscope, and under well-controlled flow boundary conditions, we
      visualized directly the transport of a tracer in a Reservoir-on-Chip (RoC)
      micromodel filled with two immiscible fluids. This study provides novel insights
      into the saturation-dependency of transport and mixing in porous media. To our
      knowledge, this is the first reported pore-scale experiment in which the
      saturation topology, relative permeability, and tortuosity were kept constant and
      transport was studied under different dynamic conditions in a wide range of
      saturation. The critical role of two-phase hydrodynamic properties on non-Fickian
      transport and saturation-dependency of dispersion are discussed, which highlight
      the major flaws in parametrization of existing models.

PMID- 28747788
TI  - Klebsiella pneumoniae Isolates from Meningitis: Epidemiology, Virulence and
      Antibiotic Resistance.
AB  - Klebsiella pneumoniae (KP) resistance to broad-spectrum cephalosporin (BSC) in
      meningitis is important because of limited therapeutic options. To investigate
      the antibiotic resistance, virulence and epidemiology of KP in meningitis, we
      conducted a retrospective study for 33 non-metastatic isolates, including primary
      meningitis (n = 20) and post-craniotomy meningitis (n = 13) collected from 1999
      to 2013. BSC resistance was found in 9 (27.3%) isolates, all from post-craniotomy
      meningitis, harboring bla SHV-5 (n = 6), bla CMY-2 (n = 2), bla DHA-1 (n = 2),
      and bla TEM-1B (n = 1). Positive virulence factors were hypermucoviscosity (n =
      22), larger bacterial size (n = 24), virulent capsule serotypes (n = 24, K2, 11;
      K1, 5; K57, 3; K5, 2; K20, 2 and K54, 1), rmpA (n = 23), rmpA 2 (n = 20),
      aerobactin gene (n = 22) and high-grade serum resistance (n = 23, 69.7%). Higher
      mouse lethality (LD50 < 106) was found in 16 isolates (48.5%). Post-craniotomy
      isolates were significantly less virulent than primary meningitis isolates,
      except for similar serum resistance capability. The pulsotype and sequence typing
      (ST) results were diverse. A minor cluster with pulsotype C and ST23 (n = 5) was
      identified in primary meningitis isolates. In conclusion, virulence factors and
      BSC resistance corresponded to about 70% and 30% of KP meningitis isolates
      respectively. BSC remains appropriate for treating primary meningitis, whereas
      meropenem is indicated for post-craniotomy meningitis empirically.

PMID- 28747789
TI  - Pressure Induced Liquid-to-Liquid Transition in Zr-based Supercooled Melts and
      Pressure Quenched Glasses.
AB  - Through high-energy x-ray diffraction and atomic pair density function analysis
      we find that Zr-based metallic alloy, heated to the supercooled liquid state
      under hydrostatic pressure and then quenched to room temperature, exhibits a
      distinct glassy structure. The PDF indicates that the Zr-Zr distances in this
      glass are significantly reduced compared to those quenched without pressure.
      Annealing at the glass transition temperature at ambient pressure reverses
      structural changes and the initial glassy state is recovered. This result
      suggests that pressure causes a liquid-to-liquid phase transition in this
      metallic alloy supercooled melt. Such a pressure induced transition is known for
      covalent liquids, but has not been observed for metallic liquids. The High
      Pressure Quenched glasses are stable in ambient conditions after decompression.

PMID- 28747790
TI  - Involvement of the leptin-adiponectin axis in inflammation and oxidative stress
      in the metabolic syndrome.
AB  - The aim of the present work was to study whether the leptin-adiponectin axis may
      have a pathophysiological role in the increased systemic inflammation and
      oxidative stress observed in patients with the metabolic syndrome (MS). Leptin,
      adiponectin, and markers of inflammation and oxidative stress were measured in a
      sample of 140 Caucasian subjects (74 males/66 females), aged 28-82 years, 60 with
      and 80 without the MS. Total concentrations of adiponectin as well as its
      multimeric forms HMW, MMW and LMW were significantly lower in individuals with
      the MS. The ratio adiponectin/leptin, a marker of dysfunctional adipose tissue,
      was dramatically decreased in the MS group. Systemic oxidative stress, as
      evidenced by levels of thiobarbituric acid reactive substances (TBARS), as well
      as markers of inflammation such as serum amyloid A (SAA), C-reactive protein
      (CRP) and osteopontin were significantly increased in subjects with the MS. Total
      adiponectin concentrations were negatively correlated with levels of TBARS and
      CRP levels. Furthermore, the ratio adiponectin/leptin was negatively correlated
      with SAA concentrations as well as with CRP levels. We concluded that a
      dysfunctional adipose tissue as suggested by a low adiponectin/leptin ratio may
      contribute to the increased oxidative stress and inflammation, hallmarks of the
      MS.

PMID- 28747791
TI  - Molecular imaging of aberrant crypt foci in the human colon targeting glutathione
      S-transferase P1-1.
AB  - Aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancers
      (CRCs), are a good surrogate marker for CRC risk stratification and
      chemoprevention. However, the conventional ACF detection method with dye-spraying
      by magnifying colonoscopy is labor- and skill-intensive. We sought to identify
      rat and human ACF using a fluorescent imaging technique that targets a molecule
      specific for ACF. We found that glutathione S-transferase (GST) P1-1 was
      overexpressed in ACF tissues in a screening experiment. We then synthesized the
      fluorogenic probe, DNAT-Me, which is fluorescently quenched but is activated by
      GSTP1-1. A CRC cell line incubated with DNAT-Me showed strong fluorescence in the
      cytosol. Fluorescence intensities correlated significantly with GST activities in
      cancer cell lines. When we sprayed DNAT-Me onto colorectal mucosa excised from
      azoxymethane-treated rats and surgically resected from CRC patients, ACF with
      strong fluorescent signals were clearly observed. The ACF number determined by
      postoperative DNAT-Me imaging was almost identical to that determined by
      preoperative methylene blue staining. The signal-to-noise ratio for ACF in DNAT
      Me images was significantly higher than that in methylene blue staining. Thus, we
      sensitively visualized ACF on rat and human colorectal mucosa by using a GST
      activated fluorogenic probe without dye-spraying and magnifying colonoscopy.

PMID- 28747792
TI  - Tailoring seed oil composition in the real world: optimising omega-3 long chain
      polyunsaturated fatty acid accumulation in transgenic Camelina sativa.
AB  - There is considerable interest in the de novo production of omega-3 long chain
      polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), not least of all given the importance of these fatty
      acids in both aquaculture and human nutrition. Previously we have demonstrated
      the feasibility of using metabolic engineering in transgenic plants (Camelina
      sativa) to modify the seed oil composition to now include EPA and/or DHA. In this
      study, we further tailored the seed oil profile to reduce the omega-6 content,
      and evaluated the performance of such GM plants under field conditions (i.e.
      environmental releases), in terms of agronomic performance and also the lipidomic
      profile of seed oil. We used MALDI- mass spectrometry imaging to identify
      discrete tissue-types in the seed in which these non-native fatty acids
      preferentially accumulated. Collectively, these data provide new insights into
      the complexity of plant lipid metabolism and the challenges associated with
      predictive manipulation of these pathways. However, this study identified the
      likely dispensable nature of a Delta12-desturase activity in our omega-3
      metabolic engineering rationales for Camelina.

PMID- 28747793
TI  - Bone matrix components activate the NLRP3 inflammasome and promote osteoclast
      differentiation.
AB  - The NLRP3 inflammasome senses a variety of signals referred to as danger
      associated molecular patterns (DAMPs), including those triggered by crystalline
      particulates or degradation products of extracellular matrix. Since some DAMPs
      confer tissue-specific activation of the inflammasomes, we tested the hypothesis
      that bone matrix components function as DAMPs for the NLRP3 inflammasome and
      regulate osteoclast differentiation. Indeed, bone particles cause exuberant
      osteoclastogenesis in the presence of RANKL, a response that correlates with
      NLRP3 abundance and the state of inflammasome activation. To determine the
      relevance of these findings to bone homeostasis, we studied the impact of Nlrp3
      deficiency on bone using pre-clinical mouse models of high bone turnover,
      including estrogen deficiency and sustained exposure to parathyroid hormone or
      RANKL. Despite comparable baseline indices of bone mass, bone loss caused by
      hormonal or RANKL perturbations is significantly reduced in Nlrp3 deficient than
      in wild type mice. Consistent with the notion that osteolysis releases DAMPs from
      bone matrix, pharmacologic inhibition of bone resorption by zoledronate
      attenuates inflammasome activation in mice. Thus, signals originating from bone
      matrix activate the NLRP3 inflammasome in the osteoclast lineage, and may
      represent a bone-restricted positive feedback mechanism that amplifies bone
      resorption in pathologic conditions of accelerated bone turnover.

PMID- 28747794
TI  - Visual perception in dyslexia is limited by sub-optimal scale selection.
AB  - Readers with dyslexia are purported to have a selective visual impairment but the
      underlying nature of the deficit remains elusive. Here, we used a combination of
      behavioural psychophysics and biologically-motivated computational modeling to
      investigate if this deficit extends to object segmentation, a process implicated
      in visual word form recognition. Thirty-eight adults with a wide range of reading
      abilities were shown random-dot displays spatially divided into horizontal
      segments. Adjacent segments contained either local motion signals in opposing
      directions or analogous static form cues depicting orthogonal orientations.
      Participants had to discriminate these segmented patterns from stimuli containing
      identical motion or form cues that were spatially intermingled. Results showed
      participants were unable to perform the motion or form task reliably when segment
      size was smaller than a spatial resolution (acuity) limit that was independent of
      reading skill. Coherence thresholds decreased as segment size increased, but for
      the motion task the rate of improvement was shallower for readers with dyslexia
      and the segment size where performance became asymptotic was larger. This
      suggests that segmentation is impaired in readers with dyslexia but only on tasks
      containing motion information. We interpret these findings within a novel
      framework in which the mechanisms underlying scale selection are impaired in
      developmental dyslexia.

PMID- 28747795
TI  - Tricritical point from high-field magnetoelastic and metamagnetic effects in UN.
AB  - Uranium nitride (UN) is one of the most studied actinide materials as it is a
      promising fuel for the next generation of nuclear reactors. Despite large
      experimental and theoretical efforts, some of the fundamental questions such as
      degree of 5 f-electron localization/delocalization and its relationship to
      magneto-vibrational properties are not resolved yet. Here we show that the
      magnetostriction of UN measured in pulsed magnetic fields up to 65 T and below
      the Neel temperature is large and exhibits complex behavior with two transitions.
      While the high field anomaly is a field-induced metamagnetic-like transition and
      affects both magnetisation and magnetostriction, the low field anomaly does not
      contribute to the magnetic susceptibility. Our data suggest a change in the
      nature of the metamagnetic transition from first to second order-like at a
      tricritical point at T tri  ~ 24 K and H tri  ~ 52 T. The induced magnetic moment
      at 60 T might suggest that only one subset of magnetic moments has aligned along
      the field direction. Using the results obtained here we have constructed a
      magnetic phase diagram of UN. These studies demonstrate that dilatometry in high
      fields is an effective method to investigate the magneto-structural coupling in
      actinide materials.

PMID- 28747796
TI  - Corrigendum: Iminimycin A, the new iminium metabolite produced by Streptomyces
      griseus OS-3601.
AB  - This corrects the article DOI: 10.1038/ja.2015.142.

PMID- 28747797
TI  - Molecular Characterization of Viral Responsive Protein 15 and Its Possible Role
      in Nuclear Export of Virus in Black Tiger Shrimp Penaeus monodon.
AB  - A viral responsive protein 15 from Penaeus monodon (PmVRP15) has been reported to
      be important for white spot syndrome virus (WSSV) infection in vivo. This work
      aims to characterize PmVRP15 and investigate its possible role in nuclear
      import/export of the virus. Circular dichroism spectra showed that PmVRP15
      contains high helical contents (82%). Analytical ultracentrifugation suggested
      that PmVRP15 could possibly form oligomers in solution. A subcellular
      fractionation study showed that PmVRP15 was found in heavy and light membrane
      fractions, indicating that PmVRP15 may be associated with endoplasmic reticulum.
      Double-stranded RNAi-mediated knockdown of PmVRP15 gene expression in vitro
      showed no effect on WSSV copy number in whole hemocyte cells. However, PmVRP15
      silencing resulted in an accumulation of WSSV DNA in the nucleus of PmVRP15
      silenced hemocytes. Immunofluorescence confocal microscopy showed that PmVRP15
      knockdown hemocytes had a much lower level of VP28 (WSSV envelope protein), in
      comparison to that in the control. It is likely that PmVRP15 may play a role in
      viral nuclear egress.

PMID- 28747799
TI  - Inflammation: Resolving - rather than suppressing - inflammation in RA might be
      the answer.

PMID- 28747798
TI  - Microbial planktonic communities in the Red Sea: high levels of spatial and
      temporal variability shaped by nutrient availability and turbulence.
AB  - The semi-enclosed nature of the Red Sea (20.2 degrees N-38.5 degrees N) makes it
      a natural laboratory to study the influence of environmental gradients on
      microbial communities. This study investigates the composition and structure of
      microbial prokaryotes and eukaryotes using molecular methods, targeting ribosomal
      RNA genes across different regions and seasons. The interaction between spatial
      and temporal scales results in different scenarios of turbulence and nutrient
      conditions allowing for testing of ecological theory that categorizes the
      response of the plankton community to these variations. The prokaryotic reads are
      mainly comprised of Cyanobacteria and Proteobacteria (Alpha and Gamma), with
      eukaryotic reads dominated by Dinophyceae and Syndiniophyceae. Periodic increases
      in the proportion of Mamiellophyceae and Bacillariophyceae reads were associated
      with alterations in the physical oceanography leading to nutrient increases
      either through the influx of Gulf of Aden Intermediate Water (south in the fall)
      or through water column mixing processes (north in the spring). We observed that
      in general dissimilarity amongst microbial communities increased when nutrient
      concentrations were higher, whereas richness (observed OTUs) was higher in
      scenarios of higher turbulence. Maximum abundance models showed the differential
      responses of dominant taxa to temperature giving an indication how taxa will
      respond as waters become warmer and more oligotrophic.

PMID- 28747800
TI  - Regenerative medicine: Breaking Prometheus's curse for cartilage regeneration.

PMID- 28747801
TI  - Osteoarthritis: Time to put steroid injections behind us?

PMID- 28747802
TI  - Rashba spin-orbit coupling in graphene monolayer coated by periodic magnetic
      stripes.
AB  - We investigate theoretically the effects of a modulated periodic perpendicular
      magnetic fields and the Rashba spin-orbit coupling (RSOC) on the electronic
      states and optical absorption spectrum in a graphene monolayer. The magnetic
      fields and supperlattice geometry give rise to distinct Dirac cone shift and open
      a finite bandgap at the Dirac point. In contrast to the energy spectrum without
      the RSOC interaction, we find that the RSOC term will develop a spin-splitting
      energy-momentum dispersion relation in this graphene magnetic supperlattice.
      Anisotropic and spin-split group velocities, effective masses and the momentum
      dependent carrier distributions along the magnetic strips are demonstrated. And
      the manipulations of these exotic properties by tuning the magnetic fields and
      the RSOC are addressed systematically. Accordingly, we find bright-to-dark
      transitions in the electron-hole pairs transition rate spectrum and absorption
      peak splitting in the optical absorption spectrum tuned by the RSOC interaction.
      This feature offers us a practical way to detect these band engineering effects
      especially the exotic spin splitting states by using the conductance and optical
      technique.

PMID- 28747803
TI  - Phylogeny of locusts and grasshoppers reveals complex evolution of density
      dependent phenotypic plasticity.
AB  - Locusts are grasshoppers that can form dense migrating swarms through an extreme
      form of density-dependent phenotypic plasticity, known as locust phase
      polyphenism. We present a comprehensive phylogeny of the genus Schistocerca,
      which contains both non-swarming grasshoppers and swarming locusts. We find that
      the desert locust, S. gregaria, which is the only Old World representative of the
      genus, is the earliest diverging lineage. This suggests that the common ancestor
      of Schistocerca must have been a swarming locust that crossed the Atlantic Ocean
      from Africa to America approximately 6 million years ago, giving rise to the
      current diversity in the New World. This also implies that density-dependent
      phenotypic plasticity is an ancestral trait for the genus. Through ancestral
      character reconstruction of reaction norms, we show that colour plasticity has
      been largely retained in most species in the genus, but behavioural plasticity
      was lost and regained at least twice. Furthermore, we show that swarming species
      do not form a monophyletic group and non-swarming species that are closely
      related to locusts often express locust-like plastic reaction norms. Thus, we
      conclude that individual reaction norms have followed different evolutionary
      trajectories, which have led to the evolutionary transition between grasshoppers
      and locusts - and vice versa.

PMID- 28747804
TI  - Differential Signalling and Kinetics of Neutrophil Extracellular Trap Release
      Revealed by Quantitative Live Imaging.
AB  - A wide variety of microbial and inflammatory factors induce DNA release from
      neutrophils as neutrophil extracellular traps (NETs). Consensus on the kinetics
      and mechanism of NET release has been hindered by the lack of distinctive methods
      to specifically quantify NET release in time. Here, we validate and refine a semi
      automatic live imaging approach for quantification of NET release. Importantly,
      our approach is able to correct for neutrophil input and distinguishes NET
      release from neutrophil death by other means, aspects that are lacking in many
      NET quantification methods. Real time visualization shows that opsonized S.
      aureus rapidly induces cell death by toxins, while actual NET formation occurs
      after 90 minutes, similar to the kinetics of NET release by immune complexes and
      PMA. Inhibition of SYK, PI3K and mTORC2 attenuates NET release upon challenge
      with physiological stimuli but not with PMA. In contrast, neutrophils from
      chronic granulomatous disease patients show decreased NET release only in
      response to PMA. With this refined method, we conclude that NET release in
      primary human neutrophils is dependent on the SYK-PI3K-mTORC2 pathway and that
      PMA stimulation should be regarded as mechanistically distinct from NET formation
      induced by natural triggers.

PMID- 28747805
TI  - An atomic carbon source for high temperature molecular beam epitaxy of graphene.
AB  - We report the use of a novel atomic carbon source for the molecular beam epitaxy
      (MBE) of graphene layers on hBN flakes and on sapphire wafers at substrate growth
      temperatures of ~1400  degrees C. The source produces a flux of predominantly
      atomic carbon, which diffuses through the walls of a Joule-heated tantalum tube
      filled with graphite powder. We demonstrate deposition of carbon on sapphire with
      carbon deposition rates up to 12 nm/h. Atomic force microscopy measurements
      reveal the formation of hexagonal moire patterns when graphene monolayers are
      grown on hBN flakes. The Raman spectra of the graphene layers grown on hBN and
      sapphire with the sublimation carbon source and the atomic carbon source are
      similar, whilst the nature of the carbon aggregates is different - graphitic with
      the sublimation carbon source and amorphous with the atomic carbon source. At MBE
      growth temperatures we observe etching of the sapphire wafer surface by the flux
      from the atomic carbon source, which we have not observed in the MBE growth of
      graphene with the sublimation carbon source.

PMID- 28747806
TI  - Brown Algae and Basalt Meal in Maintaining the Activity of Arylsulfatase of Soil
      Polluted with Cadmium.
AB  - This study analysed the effectiveness of innovative (basalt meal, brown algae
      extract) and conventional (barley straw) substances which hypothetically
      alleviate the inhibiting effect of Cd2+ on biochemical properties of soil, with
      particular regard to the activity of arylsulfatase. An analysis of their
      potential was carried out based on the activity of arylsulfatase and the number
      of Pseudomonas sp. determined on the 25th and 50th days of the study. Cd2+ was
      applied in the following doses: 0, 4, 40, 80, 120, 160, 200 mg Cd2+ kg-1 of DM
      soil, in the form of CdCl2.2.5H2O. A complex formulation of the issue was
      obtained from the presentation of biochemical properties using the RS (resistance
      of soil) index. Cadmium caused permanent adverse effects in the soil environment,
      inhibiting the activity of arylsulfatase and the yield of spring barley. The
      consequences of stress connected with increasing Cd2+ pollution were intensified
      by an elongation of the accumulation time of the tested metal in the soil.
      Chances for regeneration of the soil may be sought, most of all, with the
      application of straw and, to a lesser degree, with basalt meal. Brown algae did
      not meet the expectations for its potential. An increase in the studied
      parameters also resulted from sowing the soil with spring barley.

PMID- 28747807
TI  - Sensitivity to change in perception of speech.
AB  - Perceptual systems in all modalities are predominantly sensitive to stimulus
      change, and many examples of perceptual systems responding to change can be
      portrayed as instances of enhancing contrast. Multiple findings from perception
      experiments serve as evidence for spectral contrast explaining fundamental
      aspects of perception of coarticulated speech, and these findings are consistent
      with a broad array of known psychoacoustic and neurophysiological phenomena.
      Beyond coarticulation, important characteristics of speech perception that extend
      across broader spectral and temporal ranges may best be accounted for by the
      constant calibration of perceptual systems to maximize sensitivity to change.

PMID- 28747808
TI  - Leveraging output term co-occurrence frequencies and latent associations in
      predicting medical subject headings.
AB  - Trained indexers at the National Library of Medicine (NLM) manually tag each
      biomedical abstract with the most suitable terms from the Medical Subject
      Headings (MeSH) terminology to be indexed by their PubMed information system.
      MeSH has over 26,000 terms and indexers look at each article's full text while
      assigning the terms. Recent automated attempts focused on using the article title
      and abstract text to identify MeSH terms for the corresponding article. Most of
      these approaches used supervised machine learning techniques that use already
      indexed articles and the corresponding MeSH terms. In this paper, we present a
      new indexing approach that leverages term co-occurrence frequencies and latent
      term associations computed using MeSH term sets corresponding to a set of nearly
      18 million articles already indexed with MeSH terms by indexers at NLM. The main
      goal of our study is to gauge the potential of output label co-occurrences,
      latent associations, and relationships extracted from free text in both
      unsupervised and supervised indexing approaches. In this paper, using a novel and
      purely unsupervised approach, we achieve a micro-F-score that is comparable to
      those obtained using supervised machine learning techniques. By incorporating
      term co-occurrence and latent association features into a supervised learning
      framework, we also improve over the best results published on two public
      datasets.

PMID- 28747809
TI  - Costs, Benefits, and Adoption of Additive Manufacturing: A Supply Chain
      Perspective.
AB  - There are three primary aspects to the economics of additive manufacturing:
      measuring the value of goods produced, measuring the costs and benefits of using
      the technology, and estimating the adoption and diffusion of the technology. This
      paper provides an updated estimate of the value of goods produced. It then
      reviews the literature on additive manufacturing costs and identifies those
      instances in the literature where this technology is cost effective. The paper
      then goes on to propose an approach for examining and understanding the societal
      costs and benefits of this technology both from a monetary viewpoint and a
      resource consumption viewpoint. The final section discusses the trends in the
      adoption of additive manufacturing. Globally, there is an estimated $667 million
      in value added produced using additive manufacturing, which equates to 0.01 % of
      total global manufacturing value added. US value added is estimated as $241
      million. Current research on additive manufacturing costs reveals that it is cost
      effective for manufacturing small batches with continued centralized production;
      however, with increased automation distributed production may become cost
      effective. Due to the complexities of measuring additive manufacturing costs and
      data limitations, current studies are limited in their scope. Many of the current
      studies examine the production of single parts and those that examine assemblies
      tend not to examine supply chain effects such as inventory and transportation
      costs along with decreased risk to supply disruption. The additive manufacturing
      system and the material costs constitute a significant portion of an additive
      manufactured product; however, these costs are declining over time. The current
      trends in costs and benefits have resulted in this technology representing 0.02 %
      of the relevant manufacturing industries in the US; however, as the costs of
      additive manufacturing systems decrease, this technology may become widely
      adopted and change the supplier, manufacturer, and consumer interactions. An
      examination in the adoption of additive manufacturing reveals that for this
      technology to exceed $4.4 billion in 2020, $16.0 billion in 2025, and $196.8
      billion in 2035 it would need to deviate from its current trends of adoption.

PMID- 28747810
TI  - Differences in social preference between the sexes during ontogeny drive
      segregation in a precocial species.
AB  - ABSTRACT: Hypotheses for why animals sexually segregate typically rely on adult
      traits, such as differences in sexual roles causing differential habitat
      preferences, or size dimorphism inducing differences in diet or behaviour.
      However, segregation can occur in juveniles before such roles or size dimorphism
      is well established. In young humans, leading hypotheses suggest that (1) sexes
      differ in their activity and the synchronisation of behaviour causes segregation
      and (2) sexes separate in order to learn and maximise future reproductive roles.
      We reared pheasants, Phasianus colchicus, from hatching in the absence of adults
      in a controlled environment. Females aggregated with their own sex from hatching,
      whereas males initially exhibited random association, but segregation became
      pronounced with age. The increase in segregation corresponded to an increase in
      sexual size dimorphism. By standardising habitat availability and diet and by
      removing predation risk, we could disregard the Predation Risk and the Forage
      Selection Hypotheses operating at this age. Activity budgets did not differ
      between the sexes, providing no support for the Behavioural Synchrony or the
      Activity Budget Hypotheses. Both sexes preferentially approached groups of
      unfamiliar, same-sex birds in binary choice tests, providing support for the
      Social Preference Hypothesis. Females may segregate to avoid male aggression.
      Sexual segregation may become established early in development, especially in
      precocial species, such as pheasants. A clear understanding of ontogenetic
      factors is essential to further our understanding of adult assortment patterns.
      Assortment by sex may not be inherent, but rather emerge as a consequence of
      social interactions early in life. SIGNIFICANCE STATEMENT: Hypotheses pertaining
      to the force driving sexual segregation typically rely on adult traits, such as
      size dimorphism or differences in sexual roles. However, in some species, animals
      segregate as juveniles, so that most hypotheses previously invoked to explain
      sexual segregation in adults are irrelevant. We reared pheasants, Phasianus
      colchicus, from hatching and monitored multiple aspects of the chicks' life
      history in an effort to determine what causes sexual segregation. Females
      aggregate with their own sex from hatching, whereas males initially have a more
      random association, but segregation becomes pronounced as both sexes got older,
      coinciding with greater sexual dimorphism. We controlled for influences of
      predation risk and dietary/habitat choice and found that activity budgets did not
      differ between the sexes. Instead, we found that both sexes preferred their own
      sex when presented with a binary choice, providing evidence that social
      preference could drive sexual segregation in pheasants.

PMID- 28747811
TI  - Sharp [Formula: see text] Law for the Minimizers of the Edge-Isoperimetric
      Problem on the Triangular Lattice.
AB  - We investigate the edge-isoperimetric problem (EIP) for sets of n points in the
      triangular lattice by emphasizing its relation with the emergence of the Wulff
      shape in the crystallization problem. By introducing a suitable notion of
      perimeter and area, EIP minimizers are characterized as extremizers of an
      isoperimetric inequality: they attain maximal area and minimal perimeter among
      connected configurations. The maximal area and minimal perimeter are explicitly
      quantified in terms of n. In view of this isoperimetric characterizations, EIP
      minimizers [Formula: see text] are seen to be given by hexagonal configurations
      with some extra points at their boundary. By a careful computation of the
      cardinality of these extra points, minimizers [Formula: see text] are estimated
      to deviate from such hexagonal configurations by at most [Formula: see text]
      points. The constant [Formula: see text] is explicitly determined and shown to be
      sharp.

PMID- 28747812
TI  - Numerical Analysis of the Influence of Low Frequency Vibration on Bubble Growth.
AB  - Numerical simulation of bubble growth during pool boiling under the influence of
      low frequency vibration was performed to understand the influence of common
      vibrations such as those induced by wind, highway transportation, and nearby
      mechanical devices on the performance of thermal systems that rely on boiling.
      The simulations were done for saturated R123 boiling at 277.6 K with a 15 K wall
      superheat. The numerical volume-of-fluid method (fixed grid) was used to define
      the liquid-vapor interface. The basic bubble growth characteristics including the
      bubble departure diameter and the bubble departure time were determined as a
      function of the bubble contact angle (20 degrees -80 degrees ), the vibration
      displacement (10 um-50 um), the vibration frequency (5 Hz-25 Hz), and the initial
      vibration direction (positive or negative). The bubble parameters were shown to
      be strongly dependent on the bubble contact angle at the surface. For example,
      both the bubble departure diameter and the bubble departure time increased with
      the contact angle. At the same vibration frequency and the initial vibration
      direction, the bubble departure diameter and the bubble departure time both
      decreased with increasing vibration displacement. In addition, the vibration
      frequency had a greater effect on the bubble growth characteristics than did the
      vibration displacement. The vibration frequency effect was strongly influenced by
      the initial vibration direction. The pressure contour, the volume fraction of
      vapor phase, the temperature profile, and the velocity vector were investigated
      to understand these dynamic bubble behaviors. The limitation of the computational
      fluid dynamics approach was also described.

PMID- 28747813
TI  - Stress among Parents of Children with and without Autism Spectrum Disorder: A
      Comparison Involving Physiological Indicators and Parent Self-Reports.
AB  - Parents of children with Autism Spectrum Disorder (ASD) have been reported as
      experiencing higher levels of stress and poorer physical health than parents of
      typically developing children. However, most of the relevant literature has been
      based on parental self-reports of stress and health. While research on
      physiological outcomes has grown in recent years, gaps still exist in our
      understanding of the physiological effects, if any, of stress related to
      parenting a child with ASD. The present study compared parent-reported stress,
      anxiety, and depression, as well as selected physiological measures of stress
      (i.e., cortisol, alpha-amylase, and ambulatory blood pressure and heart rate)
      between matched groups of parents of children with (N = 38) and without (N = 38)
      ASD. Participants completed questionnaires, collected saliva samples for the
      purpose of measuring cortisol and alpha-amylase, and wore an ambulatory blood
      pressure monitor for 24 h. Parents of children with ASD reported significantly
      higher levels of parental distress, anxiety, and depression than parents of
      typically developing children. Parent-reported distress, anxiety, depression, and
      health were not correlated with physiological measures. With the exception that
      parents of children with ASD had significantly lower cortisol levels 30 min after
      waking, no other significant group differences were found for physiological
      measures. Parents of children with ASD reported significantly higher use of a
      number of adaptive coping strategies (e.g., emotional support) in comparison to
      parents of typically developing children. Results are discussed in the context of
      implications for future research directions, stress research, and practical
      implications for parental support.

PMID- 28747814
TI  - The Treatment of Anxiety in Autism Spectrum Disorder (TAASD) Study: Rationale,
      Design and Methods.
AB  - This paper describes the rationale, design, and methods of the Treatment for
      Anxiety in Autism Spectrum Disorders study, a three-site randomized controlled
      trial investigating the relative efficacy of a modular CBT protocol for anxiety
      in ASD (Behavioral Interventions for Anxiety in Children with Autism) versus
      standard CBT for pediatric anxiety (the Coping Cat program) and a treatment-as
      usual control. The trial is distinct in its scope, its direct comparison of
      active treatments for anxiety in ASD, and its comprehensive approach to assessing
      anxiety difficulties in youth with ASD. The trial will evaluate the relative
      benefits of CBT for children with ASD and investigate potential moderators (ASD
      severity, anxiety presentation, comorbidity) and mediators of treatment response,
      essential steps for future dissemination and implementation.

PMID- 28747815
TI  - Identification of very small open reading frames in the genomes of Holmes Jungle
      virus, Ord River virus, and Wongabel virus of the genus Hapavirus, family
      Rhabdoviridae.
AB  - Viruses of the family Rhabdoviridae infect a broad range of hosts from a variety
      of ecological and geographical niches, including vertebrates, arthropods, and
      plants. The arthropod-transmitted members of this family display considerable
      genetic diversity and remarkable genomic flexibility that enable coding for
      various accessory proteins in different locations of the genome. Here, we
      describe the genome of Holmes Jungle virus, isolated from Culex annulirostris
      mosquitoes collected in northern Australia, and make detailed comparisons with
      the closely related Ord River and Wongabel viruses, with a focus on identifying
      very small open reading frames (smORFs) in their genomes. This is the first
      systematic prediction of smORFs in rhabdoviruses, emphasising the intricacy of
      the rhabdovirus genome and the knowledge gaps. We speculate that these smORFs may
      be of importance to the life cycle of the virus in the arthropod vector.

PMID- 28747816
TI  - Prediction With Dimension Reduction of Multiple Molecular Data Sources for
      Patient Survival.
AB  - Predictive modeling from high-dimensional genomic data is often preceded by a
      dimension reduction step, such as principal component analysis (PCA). However,
      the application of PCA is not straightforward for multisource data, wherein
      multiple sources of 'omics data measure different but related biological
      components. In this article, we use recent advances in the dimension reduction of
      multisource data for predictive modeling. In particular, we apply exploratory
      results from Joint and Individual Variation Explained (JIVE), an extension of PCA
      for multisource data, for prediction of differing response types. We conduct
      illustrative simulations to illustrate the practical advantages and
      interpretability of our approach. As an application example, we consider
      predicting survival for patients with glioblastoma multiforme from 3 data sources
      measuring messenger RNA expression, microRNA expression, and DNA methylation. We
      also introduce a method to estimate JIVE scores for new samples that were not
      used in the initial dimension reduction and study its theoretical properties;
      this method is implemented in the R package R.JIVE on CRAN, in the function
      jive.predict.

PMID- 28747817
TI  - Conducting Systematic Outcome Assessment in Private Addictions Treatment
      Settings.
AB  - Systematic outcome assessment is central to ascertaining the impact of treatment
      services and to informing future treatment initiatives. This project was designed
      to be conducted within the clinical operations of 4 private addictions treatment
      centers. A structured interview was used to assess patients' alcohol and other
      drug use and related variables (on treatment entry and at 1, 3, and 6 months
      following treatment discharge). The primary outcomes were percentage of days
      abstinent (PDA) from alcohol and drugs, PDA from alcohol, and PDA from other
      drugs. Collateral reports during follow-up also were gathered. A total of 280
      patients (56% men) across the 4 programs participated. Percentage of days
      abstinent for each outcome increased significantly from baseline to the 1-month
      follow-up assessment, and this change was maintained at the 3- and 6-month follow
      up assessments. Collateral reports mirrored the patient follow-up reports.
      Secondary outcomes of patient ratings of urges/cravings, depression, anxiety, and
      general life functioning all indicated significant improvement from baseline over
      the course of the follow-up. The results suggest the feasibility of conducting
      systematic outcome assessment in freestanding private addictions treatment
      environments.

PMID- 28747818
TI  - An Insight of Meat Industry in Pakistan with Special Reference to Halal Meat: A
      Comprehensive Review.
AB  - Livestock is considered central component in agricultural sector of Pakistan,
      provides employment to more than 8 million families. Meat and meat products holds
      pivotal significance in meeting dietary requirements serving as major protein
      source and provide essential vitamins and minerals. Globally, consumer demand is
      increasing for healthy, hygienic and safe meat and meat products due to growing
      population, income level and food choices. As, food choices are mainly influenced
      by region, religion and economic level. However, religion is one of the major
      factor to influence the food choices. In this context, halal foods a growing
      trend, trade estimated to cross USD $ 3 trillion and among this, meat sector
      contribute about US$ 600 billion. Halal meat and allied products is requirement
      from Muslims but it is also accepted by non-Muslims due to safe and hygienic
      nature, nutritious value and superior quality. Pakistan meat industry is vibrant
      and has seen rigorous developments during last decade as government also showed
      interest to boost livestock production and processing facilities to meet
      increasing local and global demand. The industry has potential to grow owing to
      its natural animal rearing capability, muslim majority country (96% of total
      population), improvisation of market and consumer preference towards halal meat.
      Current review debates Pakistan meat industry scenario, production trend, global
      trade as well as future potential with respect to modernization, processing,
      distribution and trade. The data presented here is useful for meat producers,
      processors and people involved in export of Pakistani meat and meat based
      products.

PMID- 28747819
TI  - Physicochemical, Microbial, and Sensory Properties of Queso Blanco Cheese
      Supplemented with Powdered Microcapsules of Tomato Extracts.
AB  - The present study examined the physical, chemical, microbial, and sensory
      characteristics of Queso Blanco cheese supplemented with powdered microcapsules
      containing tomato extracts (0.5-2.0%) during storage at 7 degrees C for 60 d. The
      lactic acid bacterial count and lycopene concentrations in Queso Blanco cheese
      supplemented with powdered microcapsules were significantly higher than those of
      the control. In a texture analysis, the gumminess, chewiness, and hardness values
      for Queso Blanco cheese were significantly higher with increasing concentrations
      of the powdered microcapsules containing tomato extracts. Total short-chain fatty
      acids in Queso Blanco cheese supplemented with powdered microcapsules containing
      tomato extracts were not significantly altered compared to the control. Sensory
      evaluation scores for the yellowness, tomato taste, and firmness of Queso Blanco
      cheese were significantly higher after supplementation with powdered
      microcapsules containing tomato extracts.

PMID- 28747820
TI  - Physicochemical Properties of Meat Batter Added with Edible Silkworm Pupae
      (Bombyx mori) and Transglutaminase.
AB  - This study was conducted to investigate the physicochemical properties of meat
      batters prepared with fresh pork meat, back fat, water, and salt and formulated
      with three different amounts (5%, 10%, and 15%) of silkworm pupae (Bombyx mori)
      powder and transglutaminase (TG). Meat batters formulated with silkworm pupae
      powder showed significantly higher contents of protein and ash than control
      batter. Addition of silkworm pupae to batter also showed significantly lower
      cooking loss than the control. Moreover, meat batter containing 15% silkworm
      pupae showed no significant difference in redness value compared to the control.
      In addition, pH, viscosity, hardness, gumminess, and chewiness were improved
      after the addition of silkworm pupae. Furthermore, meat batter formulated with TG
      and silkworm pupae showed improved hardness, gumminess, chewiness and viscosity
      compared to control batter. Addition of 1% TG with 15% silkworm pupae to meat
      batter resulted in significantly higher pH, textures, and viscosity. Our data
      suggest that both silkworm pupae and TG can be added to meat batter to improve
      its physicochemical properties. Therefore, combination of silkworm pupae and TG
      could be a new nutritional and functional source for meat products.

PMID- 28747821
TI  - Effect of the Duck Skin on Quality Characteristics of Duck Hams.
AB  - This study was conducted to investigate the effect of duck skin on cooking loss,
      emulsion stability, pH, color, protein solubility, texture profile analysis
      (TPA), apparent viscosity, and sensory characteristics of press type duck ham
      with different ratio of duck breast meat and duck skin. Five duck ham
      formulations were produced with the following compositions: T1 (duck breast 70% +
      duck skin 30%), T2 (duck breast 60% + duck skin 40%), T3 (duck breast 50% + duck
      skin 50%), T4 (duck breast 40% + duck skin 60%), and T5 (duck breast 30% + duck
      skin 70%). The cooking loss and fat separation were lower in T1, and the total
      expressible fluid separations were lower in T1 and T2 than others. The pH ranged
      from 6.48 to 6.59, with the highest values in T4 and T5. T5 had the highest CIE
      L*-value, and T1 and T2 had the highest CIE a*-values; however, CIE b*-values did
      not differ significantly between the duck ham samples. The protein solubility and
      TPA (hardness, springiness, cohesiveness, gumminess, and chewiness) were the
      highest in T1. T1 and T2 had higher scores for color, tenderness, and overall
      acceptability. T1, T2, and T3 showed significantly higher values, but there were
      no significant differences for flavor and juiciness. Regarding apparent viscosity
      properties, T1 and T2 had higher viscosity values than the other formulations. In
      conclusion, the T1 (duck breast 70% + duck skin 30%) and T2 (duck breast 60% +
      duck skin 40%) duck hams show the highest quality characteristics.

PMID- 28747822
TI  - Beneficial Effect of Bifidobacterium longum ATCC 15707 on Survival Rate of
      Clostridium difficile Infection in Mice.
AB  - Clostridium difficile infection (CDI) is the main cause of hospital-acquired
      diarrhea that can cause colitis or even death. The medical-treatment cost and
      deaths caused by CDI are increasing annually worldwide. New approaches for
      prevention and treatment of these infections are needed, such as the use of
      probiotics. Probiotics, including Bifidobacterium spp. and Lactobacillus, are
      microorganisms that confer a health benefit to the host when administered in
      adequate amounts. The effect of Bifidobacterium longum ATCC 15707 on infectious
      disease caused by C. difficile 027 was investigated in a mouse model. The
      survival rates for mice given the pathogen alone, and with live cells, or dead
      cells of B. longum were 40, 70, and 60%, respectively. In addition, the
      intestinal tissues of the B. longum-treated group maintained structural integrity
      with some degree of damage. These findings suggested that B. longum ATCC 15707
      has a function in repressing the infectious disease caused by C. difficile 027.

PMID- 28747823
TI  - Effects of Beef Fat Replacement with Gelled Emulsion Prepared with Olive Oil on
      Quality Parameters of Chicken Patties.
AB  - The objective of this study was to investigate the effect of using gelled
      emulsion (olive oil 46%, inulin 9%, gelatin 3%) as fat replacer on some quality
      parameters of chicken patties. For this purpose GE, prepared with olive oil,
      gelatin and inulin was replaced with beef fat at a level of 0%, 25%, 50%, 100%
      (C, G25, G50, G100). In this study syneresis, thermal stability, centrifuge and
      creaming stability of gelled emulsion were analyzed. Chemical composition,
      technological paramerers (cooking yield, water holding capacity, diameter
      reduction, fat and moisture retention) and textural and sensory properites were
      evaluated in comparision to control patties. High thermal stability was recorded
      in GE (93%), also creaming stability results showed that GE protected its
      stability without any turbidity and separation of the layer. The complete
      replacement of beef fat with GE showed detrimental effect on all investigated
      cooking characteristics except fat retention. Replacement of beef fat with GE at
      a level of 50% resulted similar cooking characteristics with C samples. Color
      parameters of samples were affected by GE addition, higher CIE b* values observed
      with respect to GE concentration. The presence of GE significantly affected
      textural behaviors of samples (p<0.05). Our results showed that GE prepared with
      inulin and olive oil is a viable fat replacer for the manufacture of chicken
      patty.

PMID- 28747824
TI  - Effects of Carcass Weight and Back-fat Thickness on Carcass Properties of Korean
      Native Pigs.
AB  - Our study analyzed the carcass properties of 170 Korean native pigs in relation
      to carcass weight and back-fat thickness to provide general data for the
      production and distribution of high quality pig meat. The 70-74 kg group showed
      highest yield (73.41%). The >=80 kg group showed the highest thickest back-fat
      (24.13 mm) (p<0.05). The >=80 kg group showed the best quality grade (1.00). Back
      fat thickness showed significant differences in the weight among groups (p<0.05).
      The >=25 mm group showed the highest carcass weight (75.93 kg). The thickest back
      fat group (>=25 mm) showed the highest yield (73.03%). There were significant
      differences in back-fat thickness among groups (p<0.05), and the >=25 mm group
      showed the highest thickness back-fat (27.60 mm). We found a strong positive
      correlation between carcass weight and back-fat thickness (r=0.346) as well as
      meat quality grade (r=0.739). Back-fat thickness had a relatively strong positive
      correlation with meat quality grade (r=0.444). Therefore, there are required to
      manage the breeding through selection of excellent native species for increasing
      their carcass weight and enhance meat quality.

PMID- 28747825
TI  - Biological Differences between Hanwoo longissimus dorsi and semimembranosus
      Muscles in Collagen Synthesis of Fibroblasts.
AB  - Variations in physical toughness between muscles and animals are a function of
      growth rate and extend of collagen type I and III. The current study was designed
      to investigate the ability of growth rate, collagen concentration, collagen
      synthesizing and degrading genes on two different fibroblast cells derived from
      Hanwoo m. longissimus dorsi (LD) and semimembranosus (SM) muscles. Fibroblast
      cell survival time was determined for understanding about the characteristics of
      proliferation rate between the two fibroblasts. We examined the collagen
      concentration and protein expression of collagen type I and III between the two
      fibroblasts. The mRNA expression of collagen synthesis and collagen degrading
      genes to elucidate the molecular mechanisms on toughness and tenderness through
      collagen production between the two fibroblast cells. From our results the growth
      rate, collagen content and protein expression of collagen type I and III were
      significantly higher in SM than LD muscle fibroblast. The mRNA expressions of
      collagen synthesized genes were increased whereas the collagen degrading genes
      were decreased in SM than LD muscle. Results from confocal microscopical
      investigation showed increased fluorescence of collagen type I and III appearing
      stronger in SM than LD muscle fibroblast. These results implied that the
      locomotion muscle had higher fibroblast growth rate, leads to produce more
      collagen, and cause tougher than positional muscle. This in vitro study mirrored
      that background toughness of various muscles in live animal is likely associated
      with fibroblast growth pattern, collagen synthesis and its gene expression.

PMID- 28747826
TI  - Identification and Characterization of a Novel Antioxidant Peptide from Bovine
      Skim Milk Fermented by Lactococcus lactis SL6.
AB  - A novel peptide having free radical scavenging activity was separated, using an
      on-line high-performance liquid chromatography (HPLC) - ABTS screening method,
      from bovine skim milk fermented by Lactococcus lactis SL6 (KCTC 11865BP). It was
      further purified using reverse phase-HPLC (RP-HPLC) and sequenced by RP-HPLC
      tandem mass spectrometry. The amino acid sequence of the identified peptide was
      determined to be Phe-Ser-Asp-Ile-Pro-Asn-Pro-Ile-Gly-Ser-Glu-Asn-Ser-Glu-Lys-Thr
      Thr-Met-Pro-Leu-Trp (2,362 Da), which is corresponding to the C-terminal fragment
      of bovine alphas1-casein (f179-199). The hydroxyl radicals scavenging activity
      (IC50 28.25+/-0.96 MUM) of the peptide chemically synthesized based on the MS/MS
      data showed a slightly lower than that of the natural antioxidant Trolox (IC50
      15.37+/-0.52 MUM). Furthermore, derivatives of the antioxidant peptide were
      synthesized. The antioxidative activity of the derivatives whose all three
      proline residues replaced by alanine significantly decreased, whereas replacement
      of two proline residues in N-terminal region did not affect its antioxidative
      activity, indicating that 3rd proline in C-terminal region is critical for the
      antioxidative activity of the peptide identified in this study. In addition, N
      terminal region of the antioxidant peptide did not show its activity, whereas C
      terminal region maintained antioxidative activity, suggesting that C-terminal
      region of the peptide is important for antioxidative activity.

PMID- 28747827
TI  - Effect of Dietary Fiber Enrichment and Different Cooking Methods on Quality of
      Chicken Nuggets.
AB  - The effect of dietary fiber enrichment (wheat bran) and cooking methods (oven,
      steam and microwave) on functional and physico-chemical properties of raw nuggets
      formulation as well as nutritional, color and textural properties of chicken
      nuggets were analyzed in this study. Among different cooking methods used for
      nuggets preparation, steam cooked nuggets had significantly (p<0.05) higher water
      holding capacity (56.65%), cooking yield (97.16%) and total dietary fiber content
      (4.32%) in comparison to oven and microwave cooked nuggets. The effect of cooking
      methods and wheat bran incorporation was also noticed on textural properties of
      the nuggets. Hardness, firmness and toughness values of oven and steam cooked
      nuggets were significantly (p<0.05) higher than microwave cooked nuggets. Among
      nuggets prepared by different cooking methods, cohesiveness of microwave cooked
      nuggets was found to be significantly (p<0.05) highest, whereas, oven cooked
      nuggets had significantly (p<0.05) highest gumminess and chewiness values. Steam
      cooked nuggets were found to be better among all nuggets due to their higher
      cooking yield and dietary fiber content.

PMID- 28747828
TI  - Effect of Swiss Chard (Beta vulgaris var. cicla) as Nitrite Replacement on Color
      Stability and Shelf-Life of Cooked Pork Patties during Refrigerated Storage.
AB  - In this study, the effects of pre-converted nitrite from Swiss chard powder (PS)
      on the color stability and shelf-life of cooked pork patties during refrigerated
      storage for 28 d were investigated. Nitrite was added at a concentration of
      approximately 120 ppm. Five treatments were formulated as follows: Control (120
      ppm nitrite), T1 (2% PS), T2 (2% pre-converted nitrite from celery powder; PC),
      T3 (1% PS + 60 ppm nitrite), and NC (nitrite-free). The T1 and T3 samples had
      higher nitrosoheme pigment contents, which were associated with the redness of
      the samples (p<0.05). T1 resulted in the highest redness value (p<0.05). The
      redness and yellowness of the cooked pork patties increased with increasing PS
      levels. The pH of the samples subjected to all treatments decreased with progress
      of the storage period (p<0.05). The pH of the T1 and T3 samples treated with PS
      was lower (p<0.05) than that obtained with other treatments, as PS has a lower pH
      value. The treatments in which PS was added were most effective for reducing the
      level of thiobarbituric acid reactive substances (TBARS) and the residual nitrite
      content relative to the control. T1 resulted in the highest flavor, off-flavor,
      and overall acceptability scores during storage (p<0.05). The total viable
      bacterial count for all treatments was below 1 Log CFU/g, and E. coli and
      coliform bacteria were not detected during storage. Therefore, these results
      suggested that pre-converted nitrite from Swiss chard powder is a potential
      replacement for nitrite in meat products.

PMID- 28747829
TI  - Effects of Grapefruit Seed Extract on Oxidative Stability and Quality Properties
      of Cured Chicken Breast.
AB  - This study investigated the antioxidative and functional effects of a curing
      agent containing grapefruit seed extract (GSE) on the quality and storage
      characteristics of chicken breast. The total polyphenol and total flavonoid
      contents of GSE were 45.06 mg/g and 36.06 mg/g, respectively. The IC50 value of
      2,2-diphenyl-1-picrylhydrazyl hydroxyl scavenging of GSE was 333.33 MUg/mL. The
      chicken breast comprised six groups: no-treatment (N), 0.2% ascorbic acid + 70
      ppm sodium nitrite (C), 0.05% GSE (G0.05), 0.1% GSE (G0.1), 0.3% GSE (G0.3), and
      0.5% GSE (G0.5). The pH and cooking loss of cured chicken breast decreased with
      increasing GSE levels, and the water holding capacity increased with increasing
      GSE levels. The hardness and chewiness of GSE-treated chicken breast were higher
      than those of N and C. Hunter's L and a color values increased significantly
      after GSE addition. Moreover, 0.1% GSE (G0.1) increased the flavor and total
      acceptability scores. The 2-thiobarbituric acid and volatile basic nitrogen
      values of the 0.5% GSE group decreased significantly compared with those of C
      group. Total microbial counts of GSE-treated chicken breast were higher than
      those of C, but that lower than those of N. Adding GSE to chicken breast delayed
      lipid peroxidation and had antimicrobial effects during cold storage. GSE
      improved shelf life and palatability; therefore, it could be used as a natural
      antioxidant and functional curing agent ingredient in meat products.

PMID- 28747830
TI  - Effect of Aging and Freezing Conditions on Meat Quality and Storage Stability of
      1++ Grade Hanwoo Steer Beef: Implications for Shelf Life.
AB  - This study was conducted to establish the shelf life of 1++ grade Hanwoo beef by
      evaluating the changes in meat quality and storage stability under distribution
      conditions similar to those during export to Hong Kong and China. Four muscles of
      the loin, striploin, tenderloin, and top round muscles were obtained from 10
      animals of 1++ grade Hanwoo steers. The distribution conditions were 0, 7, or 14
      d of aging at 2 degrees C and continuous storage at -18 degrees C for 0, 3, 6, or
      9 mon. The lightness (CIE L*) values decreased as the duration of freezer storage
      increased (p<0.05). The water-holding capacity of 4 muscles increased as the
      aging time increased when they were frozen for 3 mon (p<0.05). The cooking loss
      values of the four muscles were significantly increased as the duration of
      freezer storage increased (p<0.05). The Warner-Bratzler shear force values were
      significantly decreased in the loin, striploin, and top round muscles as the
      aging time increased (p<0.05). The changes in volatile basic nitrogen (16.67
      18.49 mg%) and thiobarbituric reactive substance values (0.75-0.82 mg MA/kg meat)
      were significantly increased when the meat was frozen for 9 mon after 14 d of
      aging. On the basis of these observations, the shelf life of 1++ grade Hanwoo
      beef during distribution should be limited to less than 9 mon of freezer storage
      at -18 degrees C after 14 d of aging at 2 degrees C.

PMID- 28747831
TI  - Optimization of Sugar Replacement with Date Syrup in Prebiotic Chocolate Milk
      Using Response Surface Methodology.
AB  - Chocolate milk is one of the most commonly used non-fermentative dairy products,
      which, due to high level of sucrose, could lead to diabetes and tooth decay among
      children. Therefore, it is important to replace sucrose with other types of
      sweeteners, especially, natural ones. In this research, response surface
      methodology (RSM) was used to optimize the ingredients formulation of prebiotic
      chocolate milk, date syrup as sweetener (4-10%w/w), inulin as prebiotic
      texturizer (0-0.5%w/w) and carrageenan as thickening agent (0-0.04%w/w) in the
      formulation of chocolate milk. The fitted models to predict the variables of
      selected responses such as pH, viscosity, total solid, sedimentation and overall
      acceptability of chocolate milk showed a high coefficient of determination. The
      independent effect of carrageenan was the most effective parameter which led to
      pH and sedimentation decrease but increased viscosity. Moreover, in most
      treatments, date syrup and inulin variables had significant effects which had a
      mutual impact. Optimization of the variables, based on the responses surface 3D
      plots showed that the sample containing 0.48% (w/w) of inulin, 0.04% (w/w) of
      carrageenan, and 10% of date syrup was selected as the optimum condition.

PMID- 28747832
TI  - Effects of Various Calcium Powders as Replacers for Synthetic Phosphate on the
      Quality Properties of Ground Pork Meat Products.
AB  - The aim of this study was to identify the optimal and superior type of natural
      calcium for replacing phosphate in cooked ground pork products. To achieve this,
      0.5% eggshell calcium (ESC), oyster shell calcium (OSC), marine algae calcium
      (MAC), or milk calcium (MC) was added to ground pork meat products. The effect of
      this substitution was studied by comparing the substituted products with products
      containing 0.3% phosphate blend (control). ESC was considered an ideal phosphate
      replacer for minimizing the cooking loss, which likely resulted from the increase
      in the pH of the product. Among the other natural calcium types, OSC treatment
      did not cause a significant increase in pH, but it lowered the cooking loss. CIE
      L* values were higher (p<0.05) in products treated with OSC or MC than the
      control, and lowest (p<0.05) in the products with ESC. However, products with ESC
      had higher (p<0.05) CIE a* and CIE b* values than the control and products
      treated with other powders. Compared to the control, products treated with ESC
      and OSC had similar substitution effects on the textural properties of the
      products. Therefore, the results of this study suggested that the combined use of
      ESC and OSC could be a potentially effective method for replacing synthetic
      phosphate in ground pork products.

PMID- 28747833
TI  - Identification of Pork Adulteration in Processed Meat Products Using the
      Developed Mitochondrial DNA-Based Primers.
AB  - The identification of pork in commercially processed meats is one of the most
      crucial issues in the food industry because of religious food ethics, medical
      purposes, and intentional adulteration to decrease production cost. This study
      therefore aimed to develop a method for the detection of pork adulteration in
      meat products using primers specific for pig mitochondrial DNA. Mitochondrial DNA
      sequences for pig, cattle, chicken, and sheep were obtained from GenBank and
      aligned. The 294-bp mitochondrial DNA D-loop region was selected as the pig
      target DNA sequence and appropriate primers were designed using the MUSCLE
      program. To evaluate primer sensitivity, pork-beef-chicken mixtures were prepared
      as follows: i) 0% pork-50% beef-50% chicken, ii) 1% pork-49.5% beef-49.5%
      chicken, iii) 2% pork-49% beef-49% chicken, iv) 5% pork-47.5% beef-47.5% chicken,
      v) 10% pork-45% beef-45% chicken, and vi) 100% pork-0% beef-0% chicken. In
      addition, a total of 35 commercially packaged products, including patties,
      nuggets, meatballs, and sausages containing processed chicken, beef, or a mixture
      of various meats, were purchased from commercial markets. The primers developed
      in our study were able to detect as little as 1% pork in the heat treated pork
      beef-chicken mixtures. Of the 35 processed products, three samples were pork
      positive despite being labeled as beef or chicken only or as a beef-chicken mix.
      These results indicate that the developed primers could be used to detect pork
      adulteration in various processed meat products for application in safeguarding
      religious food ethics, detecting allergens, and preventing food adulteration.

PMID- 28747834
TI  - Analysis of Consumers' Preferences and Price Sensitivity to Native Chickens.
AB  - This study analyzed consumers' preferences and price sensitivity to native
      chickens. A survey was conducted from Jan 6 to 17, 2014, and data were collected
      from consumers (n=500) living in Korea. Statistical analyses evaluated the
      consumption patterns of native chickens, preference marketing for native chicken
      breeds which will be newly developed, and price sensitivity measurement (PSM). Of
      the subjects who preferred broilers, 24.3% do not purchase native chickens
      because of the dryness and tough texture, while those who preferred native
      chickens liked their chewy texture (38.2%). Of the total subjects, 38.2%
      preferred fried native chickens (38.2%) for processed food, 38.4% preferred
      direct sales for native chicken distribution, 51.0% preferred native chickens to
      be slaughtered in specialty stores, and 32.4% wanted easy access to native
      chickens. Additionally, the price stress range (PSR) was 50 won and the point of
      marginal cheapness (PMC) and point of marginal expensiveness (PME) were 6,980 won
      and 12,300 won, respectively. Evaluation of the segmentation market revealed that
      consumers who prefer broiler to native chicken breeds were more sensitive to the
      chicken price. To accelerate the consumption of newly developed native chicken
      meat, it is necessary to develop a texture that each consumer needs, to increase
      the accessibility of native chickens, and to have diverse menus and recipes as
      well as reasonable pricing for native chickens.

PMID- 28747835
TI  - Non epileptic paroxysmal events in childhood.
AB  - Non epileptic paroxysmal events are recurrent movement disorders with acute onset
      and ending, which may mimic epilepsy. The duration, place, timing of the attacks,
      and state of conciousness may confuse pediatricians about the diagnosis of
      epilepsy and non epileptic paroxysmal events. The key point in the diagnosis is
      taking an accurate and detailed history. Wrong diagnosis can give rise to anxiety
      of both the family and the child, interruptions in the child's education,
      limitations in career planning, and irreversible damages in the long term. The
      diagnosis can prevent unnecessary drug use and psychological damage. This review
      aims to discuss the clinical findings, treatment, and differential diagnoses of
      non epileptic paroxysmal events, and to increase awareness about non epileptic
      paroxysmal events among pediatricians.

PMID- 28747836
TI  - The evaluation of burnout and job satisfaction levels in residents of pediatrics.
AB  - AIM: The aim of the study was to examine the level of job-related burnout and the
      level of job satisfaction among residents of pediatrics. MATERIAL AND METHODS: A
      total of 102 residents of pediatrics who were trained in two Ministry of Health
      teaching and research hospitals and in two university hospitals in Izmir were
      included in the study. Demographic data (age, sex), lifestyle (living with
      parents or not, marital status, number of children) and professional
      characteristics (total time spent in profession, time spent in residency, number
      of night shifts per month, institution type: teaching hospital/university) were
      collected. Maslach Burnout Inventory (subscales: emotional exhaustion,
      desensitization, personal accomplishment) and Minnesota Satisfaction
      Questionnaire were used. RESULTS: High levels of emotional exhaustion and
      desensitization, and low levels of personal accomplishment and job satisfaction
      were found in residents of pediatrics. Low levels of emotional exhaustion in
      teaching and research hospitals and low levels of desensitization in university
      hospitals were determined (p<0.05). We found a positive correlation between age
      and job satisfaction levels and a negative correlation between age and emotional
      exhaustion levels (p<0.05). There were negative correlations between the length
      of time in education and desensitization and between the number of night shifts
      per month and desensitization (p<0.05). CONCLUSIONS: In residents of pediatrics,
      there is a high-level burnout and low-level of job satisfaction. Emotional
      exhaustion is more common in teaching and research hospitals and desensitization
      is more common in universities. Younger age, lower seniority, and the higher
      number of work-shift increases the burnout.

PMID- 28747837
TI  - Evaluation of pulmonary functions in preschool children born late-preterm.
AB  - AIM: The aim of this study was to evaluate the pulmonary functions of preschool
      children born late-preterm. MATERIAL AND METHODS: Children aged between 3-7 years
      who were born at 340/7-366/7 weeks' gestation represented the target sample.
      Patients with a diagnosis of congenital cardiac, pulmonary and/or muscle diseases
      were excluded. Respiratory symptoms were evaluated using the modified asthma
      predictive index and International Study of Asthma and Allergies in Childhood
      criteria for children aged under and over 6 years, respectively. Skin prick tests
      were performed. Age-matched healthy controls were chosen according to the
      criteria proposed by the American Thoracic Society. Lung functions were evaluated
      using impulse oscillometry study in both groups. Data were recorded in the SPSS
      program. RESULTS: A total of 139 late-preterms and 75 healthy controls
      participated in the study. The mean gestational week of the late-preterms was
      35.3+/-0.9 weeks. The main admission diagnosis to neonatal intensive care unit
      was respiratory distress. In the postdischarge period, 54.1% were hospitalized
      for pulmonary infections at least once, and 57.8% were passive smoking currently.
      Aeroallergen sensitivity was detected as 25.8% in the late-preterm group; 34.5%
      and 15.1% were diagnosed as having asthma and non-asthmatic atopy, respectively.
      Impulse oscillometry study parameters of R5, R10, and Z5 were higher and X10 and
      X15 were lower in late-preterms than in controls (p<0.05). Late-preterms with and
      without respiratory distress in the postnatal period revealed no statistical
      differences for any parameters. CONCLUSIONS: Our findings suggest that presence
      of increased peripheral airway resistance in late-preterms as compared to term
      born controls.

PMID- 28747838
TI  - Evaluation of nasal fluid beta-defensin 2 levels in children with allergic
      rhinitis.
AB  - AIM: Knowledge about the role of the innate immune system in the pathogenesis of
      allergic diseases has been expanding in recent years. Defensins are antimicrobial
      peptides that are components of the innate immune system. Defensins have strong
      efficacy against bacterial, viral, and fungal infections. Moreover, they have
      regulatory functions in many physiologic processes such as antitumoral immunity,
      chemotaxis, inflammation, and wound healing. In this study, we aimed to
      investigate beta-defensin 2 levels in the nasal fluids of children with allergic
      rhinitis. MATERIAL AND METHODS: Study and control groups consisted of 28 patients
      with newly diagnosed allergic rhinitis who were not taking any medication, and 23
      healthy children. Skin prick tests were performed on patients with allergic
      rhinitis and disease severity was assessed using the total symptom score. Nasal
      fluid samples were obtained using a modified polyurethane sponge absorption
      method from patients and control subjects. Nasal fluid beta-defensin 2 levels
      were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The
      median value of nasal fluid beta-defensin 2 levels were 173.8 pg/mL
      (interquartile range; 54.8-205.9 pg/mL) in allergic rhinitis group and 241.6
      pg/mL (163.5-315.2 pg/mL) in the control group. There was a statistically
      significant difference between the two groups (p=0.01). Moreover, nasal fluid
      beta-defensin 2 levels showed a significant negative correlation with total
      symptom scores (rho= -0.78, p<0.001). CONCLUSIONS: Children with allergic
      rhinitis have reduced nasal fluid beta-defensin 2 levels compared with controls,
      and beta-defensin 2 levels were negatively correlated with disease severity. A
      more definite understanding of the roles of defensins and other antimicrobial
      peptides in allergic inflammation can open up new horizons in the management and
      treatment of these common diseases.

PMID- 28747839
TI  - Etiological evaluation of primary congenital hypothyroidism cases.
AB  - AIM: Primary congenital hypothyroidism is frequently seen endocrine disorder and
      one of the preventable cause of mental retardation. Aim of study was to evaluate
      the frequency of permanent/transient hypothyrodism, and to detect underlying
      reason to identfy any marker which carries potential to discriminate
      permanent/transient form. MATERIAL AND METHODS: Forty eight cases older than 3
      years of age, diagnosed as primary congenital hypothyroidism and started thyroxin
      therapy in newborn-period, and followed up between January 2007-June 2013 were
      included in the study. Thyroid hormon levels were evaluated and thyroid
      ultrasonography was performed in cases who are at the end of their 3 years of
      age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if
      serum thyroid-stimulating hormone was high (>= 5 mIU/mL) and perchlorate
      discharge test was performed if uptake was normal or increased on sintigraphy.
      Cases with thyroid-stimulating hormone levels >= 5 mIU/mL were defined as
      permanent primary congenital hypothyroidism group and as transient primary
      congenital hypothyroidism group with normal thyroid hormones during 6 months.
      RESULTS: The mean age was 3.8+/-0.7 years. Mean diagnosis age was 16.6+/-6.5 days
      and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health.
      There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism
      group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11
      (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group,
      there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at
      diagnosis were similar in two groups. The mean thyroxin dose in permanent primary
      congenital hypothyroidism group was significantly higher than transient group at
      the time of thyroxin cessation (2.1+/-0.7, 1.5+/-0.5 mg/kg/d, respectively,
      p=0.004). Thyroxin dose >=1.6 mcg/kg/d was 72% sensitive and 69.6% specific for
      predicting permenant primary congenital hypothyroidism. CONCLUSIONS: Transient
      primary congenital hypothyroidism is more frequent than expected and found often
      in males in the primary congenital hypothyroidism cases, started thyroxin therapy
      in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at
      diagnosis do not predict transient/permenant primary congenital hypothyroidism,
      thyroxin dose before the therapy cessation at the age of 3 may make the
      distinction between transient/permenant primary congenital hypothyroidism.

PMID- 28747840
TI  - An evaluation of stillbirths in Istanbul by examining death certificates.
AB  - AIM: Despite the fact that the frequency of stillbirth is estimated to be about
      the same as that of early neonatal deaths, stillbirth records and statistics are
      not kept on a regular basis worldwide and their causes cannot be determined. The
      aim of our study was to examine the causes and characteristics of stillbirths in
      Istanbul. MATERIAL AND METHODS: All death certificates of 2011 archived in 8
      District Cemetery Directorships, which manage 322 cemeteries within the
      boundaries of Istanbul Metropolitan Municipality, were examined. Based on the
      burial licences, weight, gestational weeks, the main cause and causes of death
      related to stillbirth were analyzed. Cervical insufficieny, placenta
      abnormalities, preeclampsia, complications of multiple pregnancy, chronic
      diseases of mothers, conditions including malignancy in mothers were evaluated
      under the title of "maternal and gestational causes." Intrapartum infections,
      meconium aspiration, and asphyxia were evaluated under the title of "perinatal
      causes." RESULTS: A total of 2078 stillbirths and 128 abortus records were found
      among the death certificates. Nineteen of the abortus records and 109 stillbirths
      were misidentified. A total of 1988 stillbirth records were examined, of which
      68.4% were low-birth-weight babies (<2 500 g). Approximately three quarters of
      the stillbirths were mild preterm and extremely preterm babies, whereas 10% were
      at or more than 37 gestastional weeks. The cause of death was not known in 30% of
      the stillbirths. CONCLUSIONS: The cause of death was not known in a significant
      portion of stillbirths in Istanbul. Recordings should be made more meticulosuly
      directed to the cause of death. The cause of stillbirth in term babies is another
      research subject. Regional and global epidemiologic studies are needed to
      understand the causes of stillbirths and thus to take necessary precautions.

PMID- 28747841
TI  - Onychomadesis: A rare adverse effect in early-period valproic acid therapy.
AB  - Valproic acid is an effective, frequently used anticonvulsant drug. Typical
      adverse effects include weight gain, hair loss, and nausea. Hyperpigmentation,
      onycholysis, and onychomadesis are nail changes that can be seen after valproic
      acid use. Changes occur at the distal and proximal portions of the nail bed in
      onycholysis and onychomadesis, respectively. Onychomadesis is a very rare disease
      of childhood with the exception of systemic and genetic diseases. Here, we
      present a child aged 23 months, the youngest and the earliest isolated patient
      with onychomadesis, which occurred after valproic acid treatment and worried the
      family but resolved spontaneously. The improvement of this very rare adverse
      effect of antiepileptic drugs after cessation of valproic acid without treatment
      is emphasized.

PMID- 28747842
TI  - Combined application of extracorporeal membrane oxygenation and an artificial
      pacemaker in fulminant myocarditis in a child.
AB  - Fulminant myocarditis is severe and aggressive, but it is self-limited and
      usually has a favorable prognosis if the patients can survive the acute phase.
      When drug treatment is not effective, extracorporeal membrane oxygenation
      technology should be applied to support cardiopulmonary function. Extracorporeal
      membrane oxygenation can simultaneously support function of the left ventricle,
      right ventricle, and lungs, and provide stable blood circulation for patients
      with heart and respiratory failure, which allows sufficient time for the
      cardiopulmonary system to recover. Fulminant myocarditis affects cardiac systolic
      function, as well as the function of autorhythmic cells and the conduction
      system. If severe bradycardia or atrioventricular block appears, a pacemaker
      needs to be installed. We report a child with fulminant myocarditis who was
      treated with extracorporeal membrane oxygenation combined with an artificial
      pacemaker.

PMID- 28747843
TI  - Omalizumab's role in the treatment of steroid dependent malignant idiopathic
      anaphylaxis.
AB  - If an anaphylaxis episode is not caused by an identifiable trigger, it is defined
      as idiopathic anaphylaxis. Although it is rarely observed, idiopathic anaphylaxis
      is clinically significant because of its morbidity and fatality risk. No
      effective treatment has been demonstrated to date. We report a girl aged 16 years
      who had had malignant idiopathic anaphylaxis since the age of 12 years who was
      treated successfully with omalizumab. Although she avoided allergic trigger foods
      such as tomato and seafood, she used to have these attacks twice a week. Attacks
      were averted by taking 60 mg prednisone. When prednisone was tapered down to 5 mg
      on every alternate day, the episodes recurred. Later, attacks could not be
      controlled on <30 mg of prednisone daily. After being steroid-dependent for 4
      years, subcutaneous omalizumab 225 mg every two weeks was started. Under
      omalizumab therapy, the attacks disappeared and prednisone was discontinued.

PMID- 28747844
TI  - Posttravmatik frontoetmoidal mukopiyosel.
AB  - Paranasal sinus mucoceles are mucus-containing cystic structures with an
      epithelial lining that completely fills in the paranasal sinuses. Although they
      are benign in nature, they may result in the destruction of the surrounding bony
      structures over time. Clinical findings such as exophthalmia, visual impairment,
      and diplopia occur due to pressure of the fronto-ethmoidal mucocele on the
      orbita. Currently, the endoscopic intranasal approach is preferred in the
      treatment of paranasal sinus mucoceles due to its minimal morbidity and low
      recurrence rates. Here, we present a patient aged 12 years who had a right fronto
      ethmoidal mucopyocele secondary to a probable trauma 2 years prior, which
      resulted in proptosis due to pressure on the orbita.

PMID- 28747845
TI  - Erratum.
AB  - [This corrects the article on p. 15 in vol. 52, PMID: 28439196.].

PMID- 28747846
TI  - Strategies for the Synthesis of Higher Acenes.
AB  - The outstanding performance of pentacene-based molecules in molecular
      electronics, as well as the predicted enhanced semiconducting properties of
      extended acenes, have stimulated the development of new synthetic methods and
      functionalization strategies for the preparation of stable and soluble acenes
      larger than tetracene with the aim of obtaining improved functional materials.

PMID- 28747850
TI  - Transverse pion structure beyond leading twist in constituent models.
AB  - The understanding of the pion structure as described in terms of transverse
      momentum-dependent parton distribution functions (TMDs) is of importance for the
      interpretation of currently ongoing Drell-Yan experiments with pion beams. In
      this work we discuss the description of pion TMDs beyond leading twist in a pion
      model formulated in the light-front constituent framework. For comparison, we
      also review and derive new results for pion TMDs in the bag and spectator model.

PMID- 28747852
TI  - Energy versus centrality dependence of the jet quenching parameter [Formula: see
      text] at RHIC and LHC: a new puzzle?
AB  - The central goal of jet quenching studies in high-energy nuclear collisions is
      the characterization of those QCD medium properties that are accessible by these
      probes. Most of the discussion in the last years has been focused on the
      determination of the jet quenching parameter, [Formula: see text]. We present
      here an extraction of this parameter using data of inclusive particle suppression
      at RHIC and LHC energies for different centralities. Our approach consists in
      fitting a K factor that quantifies the departure of this parameter from an ideal
      estimate, [Formula: see text], where [Formula: see text] is determined by the
      local medium quantities as provided by hydrodynamical calculations. We find that
      this K factor is larger at RHIC than at the LHC, as obtained already in previous
      analyses, but, surprisingly, it is almost independent of the centrality of the
      collision. Taken at face value, the K factor would not depend on the local
      properties of the medium as energy density or temperature, but on global
      collision quantities such as the center of mass energy. This is a very
      intriguing, unexpected possibility for which we cannot yet provide a clear
      interpretation. We also comment on the limitations of the formalism that may
      affect this conclusion.

PMID- 28747853
TI  - The impact of the photon PDF and electroweak corrections on [Formula: see text]
      distributions.
AB  - We discuss the impact of EW corrections on differential distributions in top
      quark pair production at the LHC and future hadron colliders, focussing on the
      effects of initial-state photons. Performing a calculation at Next-to-Leading
      Order QCD+EW accuracy, we investigate in detail the impact of photon-initiated
      channels on central values as well as PDF and scale uncertainties, both at order
      [Formula: see text] and [Formula: see text]. We present predictions at 13 and 100
      TeV, and provide results for the 8 TeV differential measurements performed by
      ATLAS and CMS. A thorough comparison of results obtained with the NNPDF2.3QED and
      CT14QED PDF sets is performed. While contributions due to the photon PDF are
      negligible with CT14QED, this is not the case for NNPDF2.3QED, where such
      contributions are sizeable and show large PDF uncertainties. On the one hand, we
      show that differential observables in top-pair production, in particular top
      quark and [Formula: see text] rapidities, can be used to improve the
      determination of the photon PDF within the NNPDF approach. On the other hand,
      with current PDF sets, we demonstrate the necessity of including EW corrections
      and photon-induced contributions for a correct determination of both the central
      value and the uncertainties of theoretical predictions.

PMID- 28747855
TI  - Sleep and Anesthesia - Common mechanisms of action.

PMID- 28747856
TI  - Tunable Gas Sensing Gels by Cooperative Assembly.
AB  - The cooperative assembly of biopolymers and small molecules can yield functional
      materials with precisely tunable properties. Here, the fabrication,
      characterization, and use of multicomponent hybrid gels as selective gas sensors
      are reported. The gels are composed of liquid crystal droplets self-assembled in
      the presence of ionic liquids, which further coassemble with biopolymers to form
      stable matrices. Each individual component can be varied and acts cooperatively
      to tune gels' structure and function. The unique molecular environment in hybrid
      gels is explored for supramolecular recognition of volatile compounds. Gels with
      distinct compositions are used as optical and electrical gas sensors, yielding a
      combinatorial response conceptually mimicking olfactory biological systems, and
      tested to distinguish volatile organic compounds and to quantify ethanol in
      automotive fuel. The gel response is rapid, reversible, and reproducible. These
      robust, versatile, modular, pliant electro-optical soft materials possess new
      possibilities in sensing triggered by chemical and physical stimuli.

PMID- 28747857
TI  - Acculturation, Depression, and Smoking Cessation: a trajectory pattern
      recognition approach.
AB  - BACKGROUND: Korean Americans are known for a high smoking prevalence within the
      Asian American population. This study examined the effects of acculturation and
      depression on Korean Americans' smoking cessation and abstinence. METHODS: This
      is a secondary data analysis of a smoking cessation study that implemented eight
      weekly individualized counseling sessions of a culturally adapted cessation
      intervention for the treatment arm and a standard cognitive behavioral therapy
      for the comparison arm. Both arms also received nicotine patches for 8 weeks. A
      newly developed non-parametric trajectory pattern recognition model (MI-Fuzzy)
      was used to identify cognitive and behavioral response patterns to a smoking
      cessation intervention among 97 Korean American smokers (81 men and 16 women).
      RESULTS: Three distinctive response patterns were revealed: (a) Culturally
      Adapted (CA), since all identified members received the culturally adapted
      intervention; (b) More Bicultural (MB), for having higher scores of bicultural
      acculturation; and (c) Less Bicultural (LB), for having lower scores of
      bicultural acculturation. The CA smokers were those from the treatment arm, while
      MB and LB groups were from the comparison arm. The LB group differed in
      depression from the CA and MB groups and no difference was found between the CA
      and MB groups. Although depression did not directly affect 12-month prolonged
      abstinence, the LB group was most depressed and achieved the lowest rate of
      abstinence (LB: 1.03%; MB: 5.15%; CA: 21.65%). CONCLUSION: A culturally adaptive
      intervention should target Korean American smokers with a high level of
      depression and a low level of biculturalism to assist in their smoking cessation.
      TRIAL REGISTRATION: NCT01091363. Registered 21 March 2010.

PMID- 28747858
TI  - Smoking and secondhand smoke exposure and prevalence of depressive symptoms
      during pregnancy in Japan: baseline data from the Kyushu Okinawa Maternal and
      Child Health Study.

PMID- 28747859
TI  - Smoking in pregnancy: a cross-sectional study in China.
AB  - BACKGROUND: Findings on smoking among pregnant women were mostly from high income
      countries and were rarely from China. This study aimed to estimate the prevalence
      of smoking and its influencing factors among pregnant women living in China.
      METHODS: A cross-sectional analysis was conducted in this study. Data from
      pregnant women were collected in this study from June to August 2015 from 5
      provinces of mainland China. A total of 2345 pregnant women were included in this
      study, the mean age of the participants was 28.12 years (SD 4.13). RESULTS: About
      82.9% of smoking women quit smoking after they were pregnant. The prevalence of
      smoking among pregnant women was 3.8%. Among the participants, 40.0, 30.7, 1.8,
      29.9, 0.8, 31.4, 31.2, and 26.7% had husbands, fathers-in-law, mothers-in-law,
      fathers, mothers, colleagues, friends, and relatives, respectively, who were
      smokers. Compared with pregnant women of basic education level (junior middle
      school or below), those of the higher education level (undergraduate or above)
      were at higher risk of smoking (OR, 5.17; 95% CI, 2.00-13.39). Compared with
      pregnant women from rural areas, urban pregnant women were less likely to be
      current smokers (OR, 0.55; 95% CI, 0.32-0.94). Compared with pregnant women whose
      mothers-in-law did not smoke, those whose mothers-in-law smoked were at higher
      risk of smoking (OR, 4.67; 95% CI, 1.87-11.70). However, compared with pregnant
      women whose husband did not smoke, those whose husband smoked were not
      significantly at higher risk of smoking (OR, 1.12; 95% CI, 0.73-1.73).
      CONCLUSIONS: Most of smoking women quit smoking after they became pregnant.
      Tailored intervention programs to reduce smoking in pregnant women should focus
      on those with higher education level, from rural areas, and pregnant women whose
      mothers-in-law smoke.

PMID- 28747860
TI  - Lipolytic efficacy of alginate double-layer nanoemulsion containing oleoresin
      capsicum in differentiated 3T3-L1 adipocytes.
AB  - Background: Oleoresin capsicum (OC) is an organic extract from fruits of the
      genus Capsicum, and has been reported to have an anti-obesity effect. Objective:
      This study comparatively investigated lipolytic effects of single-layer
      nanoemulsion (SN) and alginate double-layer nanoemulsion (AN) containing OC in
      3T3-L1 adipocytes. Methods: SN and AN were compared by analyzing the
      intracellular lipid accumulation, triglyceride (TG) content, release of free
      fatty acids (FFAs) and glycerol, and mRNA expression of genes related to
      adipogenesis and lipolysis were analyzed in fully differentiated 3T3-L1
      adipocytes. Results: Compared with SN, AN exhibited higher efficiency in
      inhibiting the intracellular lipid accumulation and TG content, and enhanced the
      release of FFAs and glycerol into the medium. In AN-treated cells, mRNA levels of
      peroxisome proliferator-activated receptor-gamma and the fatty acid-binding
      protein adipocyte protein-2, which are involved in adipogenesis, were down
      regulated, whereas those of genes related to lipolysis, including hormone
      sensitive lipase and carnitine palmitoyl transferase-1alpha, were up-regulated
      compared with SN-treated cells. Conclusion: The lipolytic effect of AN was
      greater than that of SN; this was partly associated with the increased TG
      hydrolysis via induction of lipolytic gene expression and suppression of
      adipogenic gene expression in 3T3-L1 adipocytes..

PMID- 28747861
TI  - Acute fiber supplementation with inulin-type fructans curbs appetite sensations:
      a randomized, double-blind, placebo-controlled study.
AB  - Background: Research points to a benefit of inulin fiber on appetite and weight
      regulation but results remain mixed. Objectives: To test the impact of 16 g/d of
      Inulin-type fructans (ITFs) on appetite and food intake in acute settings.
      Design: Forty college age females received either a fiber drink with 16 g of ITFs
      in 330 ml water or placebo. On the 8th day of the study, appetite sensations were
      assessed using visual analogue scale (VAS) along with food intake. Repeated
      measures ANOVA were performed comparing VAS ratings during test day. Energy
      consumption was compared using paired t-tests. Significance was determined at
      p<0.05. Results: On the 8th day, the fiber group reported lower ratings for
      hunger, desire to eat, and prospective food consumption with significantly higher
      ratings for satisfaction and fullness. Subsequently, the fiber group consumed 21%
      less kcal from food at lunch (453 +/- 47 kcal) compared to controls (571 +/- 39
      kcal) (p<0.05). Conclusions: Consuming 16 g/d of ITFs in the morning for 7 days,
      and after an overnight fast, curbed appetite sensations and helped reduce food
      intake during lunch meal. These findings highlight the potential of using ITFs in
      weight management. Future studies should explore ITFs long term benefits.

PMID- 28747862
TI  - Food consumption, nutrient intake, and dietary patterns in Ghanaian migrants in
      Europe and their compatriots in Ghana.
AB  - Background: West African immigrants in Europe are disproportionally affected by
      metabolic conditions compared to European host populations. Nutrition transition
      through urbanisation and migration may contribute to this observations, but
      remains to be characterised. Objective: We aimed to describe the dietary
      behaviour and its socio-demographic factors among Ghanaian migrants in Europe and
      their compatriots living different Ghanaian settings. Methods: The multi-centre,
      cross-sectional RODAM (Research on Obesity and Diabetes among African Migrants)
      study was conducted among Ghanaian adults in rural and urban Ghana, and Europe.
      Dietary patterns were identified by principal component analysis. Results:
      Contributions of macronutrient to the daily energy intake was different across
      the three study sites. Three dietary patterns were identified. Adherence to the
      'mixed' pattern was associated with female sex, higher education, and European
      residency. The 'rice, pasta, meat, and fish' pattern was associated with male
      sex, younger age, higher education, and urban Ghanaian environment. Adherence to
      the 'roots, tubers, and plantain' pattern was mainly related to rural Ghanaian
      residency. Conclusion: We observed differences in food preferences across study
      sites: in rural Ghana, diet concentrated on starchy foods; in urban Ghana,
      nutrition was dominated by animal-based products; and in Europe, diet appeared to
      be highly diverse.

PMID- 28747863
TI  - Evaluation of the phytochemical composition and protective activities of
      methanolic extracts of Centaurea borysthenica and Centaurea daghestanica (Lipsky)
      Wagenitz on cardiomyocytes treated with doxorubicin.
AB  - Centaurea L. is a genus of the family Asteraceae that comprises over 600 taxa.
      Representatives of the Centaurea genus were used as natural medications for many
      diseases. Methanolic-aqueous extracts from aerial parts of two Centaurea species:
      C. borysthenica Gruner and C. daghestanica (Lipsky) Wagenitz were studied for
      their polyphenolic composition and potential protective effect on cardiomyocytes
      treated with doxorubicin. Effectiveness of doxorubicin in cancer therapy is
      limited by a dose-dependent cardiotoxicity. Oxidative stress is a widely
      recognized mechanism of this phenomenon. One of the most important strategies has
      been an application of drug together with antioxidant agents. A cardioprotective
      effect of selected extracts of Centaurea species was suspected in this study.
      Cell viability, oxidative stress, and mitochondrial membrane potential analyses
      showed protective activity of the methanolic extract of C. borysthenica and C.
      daghestanica on rat cardiomyocytes treated with doxorubicin. Although C.
      borysthenica is more effective as a cardiomyocyte protective agent, in higher
      concentrations it weakened the drug activity. C. daghestanica extract did not
      change the doxorubicin efficacy in the evaluated experiment. Interestingly, both
      tested extracts were cytotoxic for myeloma cells. The detected antioxidant
      activity of the studied extracts can be used in the prevention of doxorubicin
      induced cardiotoxicity.

PMID- 28747864
TI  - Research progress on theaflavins: efficacy, formation, and preparation.
AB  - Background: Theaflavins (TFs) are a category of natural compounds characterized
      with the benzotropolone skeleton. The prominent benefits of TFs have been well
      documented. Amount of research were conducted and excellent achievements were
      disclosed during the past years. However, as far as we know, there is no
      comprehensive review about TFs. Scope and approach: This review summarized the
      recent research progress. The activity of TFs on anti-oxidation, anti
      mutagenicity, hypolipidemic, anti-inflammatory, anti-cancer, anti-viral effect as
      well as the epidemiological cure were sorted. Converging pioneer literature and
      deduction, the underlying formation mechanism of TFs was proposed. Subsequently,
      acquisition of TFs was pointed out to be the fundament for further research.
      Accelerated by enzyme, bio-synthesis of TFs were reviewed simultaneously. At the
      end, employing modern analysis instrument and technology, isolations of TFs were
      enumerated. Key findings and conclusions: Structure of the skeleton as well as
      functional groups were paramount related with the bio-activity of TFs. Meanwhile,
      oxidation pathway of two catechin molecules to form TFs were hypothesized. Also,
      ascertainment of the several therapeutic efficiency of the family members of TFs
      would be the next step in the future.

PMID- 28747865
TI  - Impact of providing walnut samples in a lifestyle intervention for weight loss: a
      secondary analysis of the HealthTrack trial.
AB  - Background: Being more specific about individual food choices may be advantageous
      for weight loss. Including a healthy food (e.g. walnuts) may help to expose
      effects. Objective: To examine the impact of including walnuts in diets for
      weight loss. Design: Secondary analysis of the HealthTrack lifestyle intervention
      trial. Overweight and obese participants were randomized to: usual care (C),
      interdisciplinary intervention including individualized dietary advice (I), or
      interdisciplinary intervention including 30 g walnuts/day (IW). Changes in body
      weight, energy intake, intake of key foods, physical activity, and mental health
      over three and 12 months were explored. Results: A total of 293 participants
      completed the intensive three-month study period, and 175 had data available at
      12 months. The IW group achieved the greatest weight loss at three months. IW
      reported significant improvements in healthy food choices, and decreased intakes
      of discretionary foods/beverages, compared to C. Weight loss remained greatest in
      IW at 12 months. Discussion: Significant effects were seen after three months,
      with the IW group achieving greater weight loss and more favorable changes in
      food choices. Conclusions: Including 30 grams walnuts/day in an individualized
      diet produced weight loss and positive changes in food choice.

PMID- 28747866
TI  - Polysaccharide from wheat bran induces cytokine expression via the toll-like
      receptor 4-mediated p38 MAPK signaling pathway and prevents cyclophosphamide
      induced immunosuppression in mice.
AB  - Wheat bran-derived polysaccharides have attracted particular attention due to
      their immunomodulatory effects. However, the molecular mechanisms underlying
      their functions are poorly understood. The current study was designed to examine
      the effect of wheat bran polysaccharide (WBP) on RAW 264.7 cells and the
      underlying signaling pathways, which have not been explored. In addition, we also
      investigated the immuno-enhancement effects of WBP on cyclophosphamide (CTX)
      induced immunosuppression in mice. WBP significantly increased the concentrations
      of intracellular nitric oxide (NO) and cytokines such as prostaglandin E2 (PGE2)
      and tumor necrosis factor-alpha (TNF-alpha) in RAW 264.7 cells. The result of RT
      PCR analysis indicated that WBP also enhanced inducible nitric oxide synthase
      (iNOS), cyclooxygenase-2 (COX-2), and TNF-alpha expression. Further analyses
      demonstrated that WBP rapidly activated phosphorylated p38 mitogen-activated
      protein kinase (MAPK) and the transcriptional activities of activator protein-1
      (AP-1) and nuclear factor (NF)-kappaB via toll-like receptor 4 (TLR4).
      Furthermore, in vivo experiments revealed that WBP increased the spleen and
      thymus indices significantly, and markedly promoted the production of the serum
      cytokines IL-2 and IFN-gamma in CTX-induced immunosuppressed mice. Taken
      together, these results suggest that WBP can improve immunity by enhancing immune
      function, and could be explored as a potential immunomodulatory agent in
      functional food.

PMID- 28747867
TI  - Associations between fish intake and the metabolic syndrome and its components
      among middle-aged men and women: the Hordaland Health Study.
AB  - In epidemiologic studies, the relationship between fish consumption and the
      metabolic syndrome (MetS) have been inconclusive and sex differences reported.
      The aim was to investigate associations between fish intake and the MetS in a
      cross-sectional study of men and women. Fish intake, waist circumference,
      triglycerides (TG), HDL-C, glucose and blood pressure were assessed among 2874
      men and women (46-49 y) in the Hordaland Health Study (1997-1999). Fatty fish
      intake was inversely associated with TG in men only; mean difference in TG
      between highest and lowest quartile of fatty fish intake was -0.33 mmol/L (95%
      CI: -0.51, -0.15). Lean fish intake was inversely associated with TG in women
      only; mean difference in TG between highest and lowest quartile of lean fish
      intake was -0.23 mmol/L (95% CI: -0.34, -0.11). Fatty fish intake was positively
      associated with serum HDL-C in both men and women. Total fish intake was
      inversely associated with MetS; adjusted OR 0.75 (95% CI 0.57, 0.97). Higher fish
      intake was associated with lower odds of having MetS possibly driven by
      associations of higher fish intake with lower TG and higher HDL-C. The findings
      of differential associations by sex needs to be confirmed and possible biologic
      mechanisms explored.

PMID- 28747868
TI  - Protective effect of Momordica charantia water extract against liver injury in
      restraint-stressed mice and the underlying mechanism.
AB  - Background: Momordica charantia is used in China for its jianghuo (heat-clearing
      and detoxifying) effects. The concept of shanghuo (the antonym of jianghuo,
      excessive internal heat) in traditional Chinese medicine is considered a type of
      stress response of the body. The stress process involves internal organs,
      especially the liver. Objective: We hypothesized that Momordica charantia water
      extract (MWE) has a hepatoprotective effect and can protect the body from stress.
      The aim of this study was to investigate the possible effects of MWE against
      liver injury in restraint-stressed mice. Design: The mice were intragastrically
      administered with MWE (250, 500 and 750 mg/kg bw) daily for 7 days. The Normal
      Control (NC) and Model groups were administered distilled water. A positive
      control group was intragastrically administered vitamin C 250 mg/kg bw. After the
      last administration, mice were restrained for 20 h. Results: MWE reduced the
      serum AST and ALT, reduced the NO content and the protein expression level of
      iNOSin the liver; significantly reduced the mitochondrial ROS content, increased
      the mitochondrial membrane potential and the activities of mitochondrial
      respiratory chain complexes I and II in restraint-stressed mice. Conclusions: The
      results indicate that MWE has a protective effect against liver injury in
      restraint-stressed mice. Abbreviations: MWE: Momordica charantia water extract;
      M. charantia: Momordica charantia L.; ROS: reactive oxygen species; NO: nitric
      oxide; iNOS: inducible nitric oxide synthase; IL-1beta: interleukin-1 beta; TNF
      alpha: tumor necrosis factor alpha; IL-6: interleukin 6; IFN-gamma: interferon
      gamma; VC: vitamin C; ALT: alanine transaminase; AST: aspartate aminotransferase;
      GSH: glutathione; GSH-PX: glutathione peroxidase; MDA: malondialdehyde; BCA:
      bicinchoninic acid; TBARS: thiobarbituric acid reactive substances; Trolox: 6
      hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; JC-B: Janus Green B; DW:
      dry weight; FC: Folin-Ciocalteu; GAE: gallic acid equivalents; bw: body weight;
      NC: normal control group; Model: restraint stress model group; VC: positive
      control vitamin C group, 250 mg/kg bw; MWEL: Momordica charantia water extract
      low-dose group, 250 mg/kg bw; MWEM: Momordica charantia water extract middle-dose
      group, 500 mg/kg bw; MWEH: Momordica charantia water extract high-dose group, 750
      mg/kg bw; HE: hematoxylin and eosin; ORAC: total oxygen radical absorbance
      capacity; ABAP: dihydrochloride; ATP: adenosine triphosphate.

PMID- 28747869
TI  - Effect of dietary copper addition on lipid metabolism in rabbits.
AB  - The present study was conducted to investigate the effect of copper
      supplementation on lipid metabolism in rabbits. Our study showed dietary copper
      addition (5-45 mg/kg) increased body mass gain, but decreased fat and liver
      weights compared with those in the control group (P < 0.05). Copper (45 mg/kg)
      addition significantly increased the skeletal muscle weight, but inhibited
      cytoplasmic lipid accumulation in liver, skeletal muscle and adipose tissue (P <
      0.05). Compared with the control group, dietary copper addition (45 mg/kg)
      significantly increased plasma triglyceride levels but decreased very low density
      lipoprotein levels (P < 0.05). Copper treatment significantly increased gene
      expression of carnitine palmitoyltransferase (CPT) 1, CPT2 and peroxisome
      proliferator-activated receptor (PPAR) a in liver (P < 0.05). In skeletal muscle,
      CPT1, CPT2, fatty acid transport protein, fatty acid-binding protein, and PPARa
      mRNA as well as phosphorylated AMP-activated protein kinase (AMPK) levels were
      significantly up-regulated by copper treatment (P < 0.05). Rabbits receiving
      copper supplementation had higher CPT1, CPT2, PPARa and hormone-sensitive lipase
      mRNA levels in adipose tissue (P < 0.05). In conclusion, copper promoted skeletal
      muscle growth and reduced fat accretion. PPARa signaling in liver, skeletal
      muscle and adipose tissues and AMPK signaling in skeletal muscle tissue were
      involved in the regulation of lipid metabolism by copper.

PMID- 28747870
TI  - Neural Entrainment and Sensorimotor Synchronization to the Beat in Children with
      Developmental Dyslexia: An EEG Study.
AB  - Tapping in time to a metronome beat (hereafter beat synchronization) shows
      considerable variability in child populations, and individual differences in beat
      synchronization are reliably related to reading development. Children with
      developmental dyslexia show impairments in beat synchronization. These
      impairments may reflect deficiencies in auditory perception of the beat which in
      turn affect auditory-motor mapping, or may reflect an independent motor deficit.
      Here, we used a new methodology in EEG based on measuring beat-related steady
      state evoked potentials (SS-EPs, Nozaradan et al., 2015) in an attempt to
      disentangle neural sensory and motor contributions to behavioral beat
      synchronization in children with dyslexia. Children tapped with both their left
      and right hands to every second beat of a metronome pulse delivered at 2.4 Hz, or
      listened passively to the beat. Analyses of preferred phase in EEG showed that
      the children with dyslexia had a significantly different preferred phase compared
      to control children in all conditions. Regarding SS-EPs, the groups differed
      significantly for the passive Auditory listening condition at 2.4 Hz, and showed
      a trend toward a difference in the Right hand tapping condition at 3.6 Hz
      (sensorimotor integration measure). The data suggest that neural rhythmic
      entrainment is atypical in children with dyslexia for both an auditory beat and
      during sensorimotor coupling (tapping). The data are relevant to a growing
      literature suggesting that rhythm-based interventions may help language
      processing in children with developmental disorders of language learning.

PMID- 28747871
TI  - Age and Glaucoma-Related Characteristics in Retinal Nerve Fiber Layer and
      Choroid: Localized Morphometrics and Visualization Using Functional Shapes
      Registration.
AB  - Optical coherence tomography provides high-resolution 3D imaging of the posterior
      segment of the eye. However, quantitative morphological analysis, particularly
      relevant in retinal degenerative diseases such as glaucoma, has been confined to
      simple sectorization and averaging with limited spatial sensitivity for detection
      of clinical markers. In this paper, we present point-wise analysis and
      visualization of the retinal nerve fiber layer and choroid from cross-sectional
      data using functional shapes (fshape) registration. The fshape framework matches
      two retinas, or generates a mean of multiple retinas, by jointly optimizing the
      surface geometry and functional signals mapped on the surface. We generated group
      wise mean retinal nerve fiber layer and choroidal surfaces with the respective
      layer thickness mapping and showed the difference by age (normal, younger vs.
      older) and by disease (age-matched older, normal vs. glaucomatous) in the two
      layers, along with a more conventional sector-based analysis for comparison. The
      fshape results visualized the detailed spatial patterns of the differences
      between the age-matched normal and glaucomatous retinal nerve fiber layers, with
      the glaucomatous layers most significantly thinner in the inferior region close
      to Bruch's membrane opening. Between the young and older normal cases, choroid
      was shown to be significantly thinner in the older subjects across all regions,
      but particularly in the nasal and inferior regions. The results demonstrate a
      comprehensive and detailed analysis with visualization of morphometric patterns
      by multiple factors.

PMID- 28747872
TI  - L-3-n-Butylphthalide Protects HSPB8 K141N Mutation-Induced Oxidative Stress by
      Modulating the Mitochondrial Apoptotic and Nrf2 Pathways.
AB  - Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory
      neuropathy, is the most common inherited peripheral nerve disorder. Missense
      mutations, such as K141N, in the small heat shock protein HSPB8 are known to
      cause distal hereditary motor neuropathy 2A (dHMN2A) or Charcot-Marie-Tooth
      neuropathy type 2L (CMT2L). However, of critical clinical significance, very few
      specific therapies for this disease exist. In the present study, we investigated
      the impact of mutant K141N HSPB8 on mitochondrial distribution and function in a
      cellular model of CMT2L. Our results indicate that K141N HSPB8 induced
      mitochondrial aggregation and caused increased oxidative stress injury. As an
      extraction from Chinese celery Apium graveolens Linn seeds, L-3-n-Butylphthalide
      (NBP), has been reported to exert many neuroprotective effects, we interrogated
      whether NBP could elicit a protective effect on the cell injury typically caused
      by HSPB8 K141N mutations. We found NBP could reverse the pathological processes
      induced by HSPB8 K141N mutation via an antioxidant effect, modulation of the
      Bax/Bcl-2 mitochondrial apoptotic and Nrf2 pathways. We propose a novel function
      of HSPB8, highlighting the consequence of the K141N pathogenic mutation.
      Furthermore, we suggest NBP may have promising therapeutic potential in the
      treatment of CMT2L.

PMID- 28747874
TI  - The Functioning of a Cortex without Layers.
AB  - A major hallmark of cortical organization is the existence of a variable number
      of layers, i.e., sheets of neurons stacked on top of each other, in which neurons
      have certain commonalities. However, even for the neocortex, variable numbers of
      layers have been described and it is just a convention to distinguish six layers
      from each other. Whether cortical layers are a structural epiphenomenon caused by
      developmental dynamics or represent a functionally important modularization of
      cortical computation is still unknown. Here we present our insights from the
      reeler mutant mouse, a model for a developmental, "molecular lesion"-induced loss
      of cortical layering that could serve as ground truth of what an intact layering
      adds to the cortex in terms of functionality. We could demonstrate that the
      reeler neocortex shows no inversion of cortical layers but rather a severe
      disorganization that in the primary somatosensory cortex leads to the complete
      loss of layers. Nevertheless, the somatosensory system is well organized. When
      exploring an enriched environment with specific sets of whiskers, activity
      dependent gene expression takes place in the corresponding modules. Precise
      whisker stimuli lead to the functional activation of somatotopically organized
      barrel columns as visualized by intrinsic signal optical imaging. Similar results
      were obtained in the reeler visual system. When analyzing pathways that could be
      responsible for preservation of tactile perception, lemniscal thalamic
      projections were found to be largely intact, despite the smearing of target
      neurons across the cortical mantle. However, with optogenetic experiments we
      found evidence for a mild dispersion of thalamic synapse targeting on layer IV
      spiny stellate cells, together with a general weakening in thalamocortical input
      strength. This weakening of thalamic inputs was compensated by intracortical
      mechanisms involving increased recurrent excitation and/or reduced feedforward
      inhibition. In conclusion, a layer loss so far only led to the detection of
      subtle defects in sensory processing by reeler mice. This argues in favor of a
      view in which cortical layers are not an essential component for basic perception
      and cognition. A view also supported by recent studies in birds, which can have
      remarkable cognitive capacities despite the lack of a neocortex with multiple
      cortical layers. In conclusion, we suggest that future studies directed toward
      understanding cortical functions should rather focus on circuits specified by
      functional cell type composition than mere laminar location.

PMID- 28747873
TI  - Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in
      Perinatal Brain Injury.
AB  - Injury to the fragile immature brain is implicated in the manifestation of long
      term neurological disorders, including childhood disability such as cerebral
      palsy, learning disability and behavioral disorders. Advancements in perinatal
      practice and improved care mean the majority of infants suffering from perinatal
      brain injury will survive, with many subtle clinical symptoms going undiagnosed
      until later in life. Hypoxic-ischemia is the dominant cause of perinatal brain
      injury, and constitutes a significant socioeconomic burden to both developed and
      developing countries. Therapeutic hypothermia is the sole validated clinical
      intervention to perinatal asphyxia; however it is not always neuroprotective and
      its utility is limited to developed countries. There is an urgent need to better
      understand the molecular pathways underlying hypoxic-ischemic injury to identify
      new therapeutic targets in such a small but critical therapeutic window.
      Mitochondria are highly implicated following ischemic injury due to their roles
      as the powerhouse and main energy generators of the cell, as well as cell death
      processes. While the link between impaired mitochondrial bioenergetics and
      secondary energy failure following loss of high-energy phosphates is well
      established after hypoxia-ischemia (HI), there is emerging evidence that the
      roles of mitochondria in disease extend far beyond this. Indeed, mitochondrial
      turnover, including processes such as mitochondrial biogenesis, fusion, fission
      and mitophagy, affect recovery of neurons after injury and mitochondria are
      involved in the regulation of the innate immune response to inflammation. This
      review article will explore these mitochondrial pathways, and finally will
      summarize past and current efforts in targeting these pathways after hypoxic
      ischemic injury, as a means of identifying new avenues for clinical intervention.

PMID- 28747875
TI  - Effects of High-Definition Anodal Transcranial Direct Current Stimulation Applied
      Simultaneously to Both Primary Motor Cortices on Bimanual Sensorimotor
      Performance.
AB  - Many daily activities, such as tying one's shoe laces, opening a jar of jam or
      performing a free throw in basketball, require the skillful coordinated use of
      both hands. Even though the non-invasive method of transcranial direct current
      stimulation (tDCS) has been repeatedly shown to improve unimanual motor
      performance, little is known about its effects on bimanual motor performance.
      More knowledge about how tDCS may improve bimanual behavior would be relevant to
      motor recovery, e.g., in persons with bilateral impairment of hand function. We
      therefore examined the impact of high-definition anodal tDCS (HD-atDCS) on the
      performance of a bimanual sequential sensorimotor task. Thirty-two volunteers
      (age M = 24.25; SD = 2.75; 14 females) participated in this double-blind study
      and performed sport stacking in six experimental sessions. In sport stacking, 12
      specially designed cups must be stacked (stacked up) and dismantled (stacked
      down) in predefined patterns as fast as possible. During a pretest, posttest and
      follow-up test, two sport stacking formations (3-6-3 stack and 1-10-1 stack) were
      performed. Between the pretest and posttest, all participants were trained in
      sport stacking with concurrent brain stimulation for three consecutive days. The
      experimental group (STIM-M1) received HD-atDCS over both primary motor cortices
      (M1), while the control group received a sham stimulation (SHAM). Three-way
      analysis of variance (ANOVA) revealed a significant main effect of TIME and a
      significant interaction of TIME * GROUP. No significant effects were found for
      GROUP, nor for the three-way interaction of TIME * GROUP * FORMATION. Further two
      way ANOVAs showed a significant main effect of TIME and a non-significant main
      effect for GROUP in both sport stacking formations. A significant interaction
      between TIME * GROUP was found only for the 3-6-3 formation, indicating superior
      performance gains for the experimental group (STIM-M1). To account and control
      for baseline influences on the outcome measurements, ANCOVAs treating pretest
      scores as covariates revealed a significant effect of the stimulation. From this,
      we conclude that bilateral HD-atDCS over both M1 improves motor performance in a
      bimanual sequential sensorimotor task. These results may indicate a beneficial
      use of tDCS for learning and recovery of bimanual motor skills.

PMID- 28747876
TI  - Structural Correlates of Reading the Mind in the Eyes in Autism Spectrum
      Disorder.
AB  - Behavioral studies have shown that individuals with autism spectrum disorder
      (ASD) have impaired ability to read the mind in the eyes. Although this
      impairment is central to their social malfunctioning, its structural neural
      correlates remain unclear. To investigate this issue, we assessed Reading the
      Mind in the Eyes Test, revised version (Eyes Test) and acquired structural
      magnetic resonance images in adults with high-functioning ASD (n = 19) and age-,
      sex- and intelligence quotient-matched typically developing (TD) controls (n =
      19). On the behavioral level, the Eyes Test scores were lower in the ASD group
      than in the control group. On the neural level, an interaction between group and
      Eyes Test score was found in the left temporoparietal junction (TPJ). A positive
      association between the Eyes Test score and gray matter volume of this region was
      evident in the control group, but not in the ASD group. This finding suggests
      that the failure to develop appropriate structural neural representations in the
      TPJ may underlie the impaired ability of individuals with ASD to read the mind in
      the eyes. These behavioral and neural findings provide support for the theories
      that impairments in processing eyes and the ability to infer others' mental
      states are the core symptoms of ASD, and that atypical features in the social
      brain network underlie such impairments.

PMID- 28747877
TI  - Combining Multiple Resting-State fMRI Features during Classification: Optimized
      Frameworks and Their Application to Nicotine Addiction.
AB  - Machine learning techniques have been applied to resting-state fMRI data to
      predict neurological or neuropsychiatric disease states. Existing studies have
      used either a single type of resting-state feature or a few feature types (<4) in
      the prediction model. However, resting-state data can be processed in many
      different ways, yielding different feature types containing complementary and/or
      novel information, leaving uncertain the most informative features to provide to
      the classifier. In this study, multiple resting-state features were calculated
      from two main analytical categories: local measures and network measures. Feature
      selection was adopted using an optimized grid-search approach selecting top
      ranked features from statistical tests. We then tested three optimized
      frameworks: feature combination, kernel combination, and classifier combination,
      all using the support vector machine as an elementary classifier, to combine
      these resting-state feature types. When applied to nicotine addiction, with a
      cohort size of 100 smokers and 100 non-smokers, via a 10-fold cross-validation
      procedure, the feature combination and the classifier combination achieved an
      accuracy of 75.5%, while the kernel combination achieved a 73.0% accuracy; all
      three combination frameworks improved classification performance compared to the
      single feature type based results (best accuracy 70.5%). This study not only
      reveals the discriminative power of resting-state data, but also demonstrates the
      efficiency of combining multiple features from one data phenotype to improve
      classification performance.

PMID- 28747878
TI  - Transcranial Electric Stimulation Can Impair Gains during Working Memory Training
      and Affects the Resting State Connectivity.
AB  - Transcranial electric stimulation (tES) is a promising technique that has been
      shown to improve working memory (WM) performance and enhance the effect of
      cognitive training. However, experimental set up and electrode placement are not
      always determined based on neurofunctional knowledge about WM, leading to
      inconsistent results. Additional research on the effects of tES grounded on
      neurofunctional evidence is therefore necessary. Sixty young, healthy,
      volunteers, assigned to six different groups, participated in 5 days of
      stimulation or sham treatment. Twenty-five of these subjects also participated in
      MRI acquisition. We performed three experiments: In the first one, we evaluated
      tES using either direct current stimulation (tDCS) with bilateral stimulation of
      the frontal or parietal lobe; in the second one, we used the same tDCS protocol
      with a different electrode placement (i.e., supraorbital cathode); in the third
      one, we used alternating currents (tACS) of 35 Hz, applied bilaterally to either
      the frontal or parietal lobes. The behavioral outcome measure was the WM capacity
      (i.e., number of remembered spatial position) during the 5 days of training. In a
      subsample of subjects we evaluated the neural effects of tDCS by measuring
      resting state connectivity with functional MRI, before and after the 5 days of
      tDCS and visuo-spatial WM training. We found a significant impairment of WM
      training-related gains associated with parietal tACS and frontal tDCS. Five days
      of tDCS stimulation was also associated with significant change in resting state
      connectivity revealed by multivariate pattern analysis. None of the stimulation
      paradigms resulted in improved WM performance or enhanced WM training gains.
      These results show that tES can have negative effects on cognitive plasticity and
      affect resting-state functional connectivity.

PMID- 28747879
TI  - Prediction of Mind-Wandering with Electroencephalogram and Non-linear Regression
      Modeling.
AB  - Mind-wandering (MW), task-unrelated thought, has been examined by researchers in
      an increasing number of articles using models to predict whether subjects are in
      MW, using numerous physiological variables. However, these models are not
      applicable in general situations. Moreover, they output only binary
      classification. The current study suggests that the combination of
      electroencephalogram (EEG) variables and non-linear regression modeling can be a
      good indicator of MW intensity. We recorded EEGs of 50 subjects during the
      performance of a Sustained Attention to Response Task, including a thought
      sampling probe that inquired the focus of attention. We calculated the power and
      coherence value and prepared 35 patterns of variable combinations and applied
      Support Vector machine Regression (SVR) to them. Finally, we chose four SVR
      models: two of them non-linear models and the others linear models; two of the
      four models are composed of a limited number of electrodes to satisfy model
      usefulness. Examination using the held-out data indicated that all models had
      robust predictive precision and provided significantly better estimations than a
      linear regression model using single electrode EEG variables. Furthermore, in
      limited electrode condition, non-linear SVR model showed significantly better
      precision than linear SVR model. The method proposed in this study helps
      investigations into MW in various little-examined situations. Further, by
      measuring MW with a high temporal resolution EEG, unclear aspects of MW, such as
      time series variation, are expected to be revealed. Furthermore, our suggestion
      that a few electrodes can also predict MW contributes to the development of neuro
      feedback studies.

PMID- 28747880
TI  - Strong Functional Connectivity among Homotopic Brain Areas Is Vital for Motor
      Control in Unilateral Limb Movement.
AB  - The mechanism underlying brain region organization for motor control in humans
      remains poorly understood. In this functional magnetic resonance imaging (fMRI)
      study, right-handed volunteers were tasked to maintain unilateral foot movements
      on the right and left sides as consistently as possible. We aimed to identify the
      similarities and differences between brain motor networks of the two conditions.
      We recruited 18 right-handed healthy volunteers aged 25 +/- 2.3 years and used a
      whole-body 3T system for magnetic resonance (MR) scanning. Image analysis was
      performed using SPM8, Conn toolbox and Brain Connectivity Toolbox. We determined
      a craniocaudally distributed, mirror-symmetrical modular structure. The
      functional connectivity between homotopic brain areas was generally stronger than
      the intrahemispheric connections, and such strong connectivity led to the
      abovementioned modular structure. Our findings indicated that the
      interhemispheric functional interaction between homotopic brain areas is more
      intensive than the interaction along the conventional top-down and bottom-up
      pathways within the brain during unilateral limb movement. The detected strong
      interhemispheric horizontal functional interaction is an important aspect of
      motor control but often neglected or underestimated. The strong interhemispheric
      connectivity may explain the physiological phenomena and effects of promising
      therapeutic approaches. Further accurate and effective therapeutic methods may be
      developed on the basis of our findings.

PMID- 28747881
TI  - Frequency-Unspecific Effects of theta-tACS Related to a Visuospatial Working
      Memory Task.
AB  - Working memory (WM) is crucial for intelligent cognitive functioning, and
      synchronization phenomena in the fronto-parietal network have been suggested as
      an underlying neural mechanism. In an attempt to provide causal evidence for this
      assumption, we applied transcranial alternating current stimulation (tACS) at
      theta frequency over fronto-parietal sites during a visuospatial match-to-sample
      (MtS) task. Depending on the stimulation protocol, i.e., in-phase, anti-phase or
      sham, we anticipated a differential impact of tACS on behavioral WM performance
      as well as on the EEG (electroencephalography) during resting state before and
      after stimulation. We hypothesized that in-phase tACS of the fronto-parietal
      theta network (stimulation frequency: 5 Hz; intensity: 1 mA peak-to-peak) would
      result in performance enhancement, whereas anti-phase tACS would cause
      performance impairment. Eighteen participants (nine female) received in-phase,
      anti-phase, and sham stimulation in balanced order. While being stimulated,
      subjects performed the MtS task, which varied in executive demand (two levels:
      low and high). EEG analysis of power peaks within the delta (0.5-4 Hz), theta (4
      8 Hz), alpha (8-12 Hz), and beta (12-30 Hz) frequency bands was carried out. No
      significant differences were observed between in-phase and anti-phase stimulation
      regarding both behavioral and EEG measurements. Yet, with regard to the alpha
      frequency band, we observed a statistically significant drop of peak power from
      pre to post in the sham condition, whereas alpha power remained on a similar
      level in the actively stimulated conditions. Our results indicate a frequency
      unspecific modulation of neuronal oscillations by tACS. However, the closer
      participants' individual theta peak frequencies were to the stimulation frequency
      of 5 Hz after anti-phase tACS, the faster they responded in the MtS task. This
      effect did not reach statistical significance during in-phase tACS and was not
      present during sham. A lack of statistically significant behavioral results in
      the MtS task and frequency-unspecific effects on the electrophysiological level
      question the effectiveness of tACS in modulating cortical oscillations in a
      frequency-specific manner.

PMID- 28747882
TI  - Comparison of IT Neural Response Statistics with Simulations.
AB  - Lehky et al. (2011) provided a statistical analysis on the responses of the
      recorded 674 neurons to 806 image stimuli in anterior inferotemporalm (AIT)
      cortex of two monkeys. In terms of kurtosis and Pareto tail index, they observed
      that the population sparseness of both unnormalized and normalized responses is
      always larger than their single-neuron selectivity, hence concluded that the
      critical features for individual neurons in primate AIT cortex are not very
      complex, but there is an indefinitely large number of them. In this work, we
      explore an "inverse problem" by simulation, that is, by simulating each neuron
      indeed only responds to a very limited number of stimuli among a very large
      number of neurons and stimuli, to assess whether the population sparseness is
      always larger than the single-neuron selectivity. Our simulation results show
      that the population sparseness exceeds the single-neuron selectivity in most
      cases even if the number of neurons and stimuli are much larger than several
      hundreds, which confirms the observations in Lehky et al. (2011). In addition, we
      found that the variances of the computed kurtosis and Pareto tail index are quite
      large in some cases, which reveals some limitations of these two criteria when
      used for neuron response evaluation.

PMID- 28747883
TI  - Obstacle Avoidance and Target Acquisition for Robot Navigation Using a Mixed
      Signal Analog/Digital Neuromorphic Processing System.
AB  - Neuromorphic hardware emulates dynamics of biological neural networks in
      electronic circuits offering an alternative to the von Neumann computing
      architecture that is low-power, inherently parallel, and event-driven. This
      hardware allows to implement neural-network based robotic controllers in an
      energy-efficient way with low latency, but requires solving the problem of device
      variability, characteristic for analog electronic circuits. In this work, we
      interfaced a mixed-signal analog-digital neuromorphic processor ROLLS to a
      neuromorphic dynamic vision sensor (DVS) mounted on a robotic vehicle and
      developed an autonomous neuromorphic agent that is able to perform neurally
      inspired obstacle-avoidance and target acquisition. We developed a neural network
      architecture that can cope with device variability and verified its robustness in
      different environmental situations, e.g., moving obstacles, moving target,
      clutter, and poor light conditions. We demonstrate how this network, combined
      with the properties of the DVS, allows the robot to avoid obstacles using a
      simple biologically-inspired dynamics. We also show how a Dynamic Neural Field
      for target acquisition can be implemented in spiking neuromorphic hardware. This
      work demonstrates an implementation of working obstacle avoidance and target
      acquisition using mixed signal analog/digital neuromorphic hardware.

PMID- 28747884
TI  - Geomagnetic Navigation of Autonomous Underwater Vehicle Based on Multi-objective
      Evolutionary Algorithm.
AB  - This paper presents a multi-objective evolutionary algorithm of bio-inspired
      geomagnetic navigation for Autonomous Underwater Vehicle (AUV). Inspired by the
      biological navigation behavior, the solution was proposed without using a priori
      information, simply by magnetotaxis searching. However, the existence of the
      geomagnetic anomalies has significant influence on the geomagnetic navigation
      system, which often disrupts the distribution of the geomagnetic field. An
      extreme value region may easily appear in abnormal regions, which makes AUV lost
      in the navigation phase. This paper proposes an improved bio-inspired algorithm
      with behavior constraints, for sake of making AUV escape from the abnormal
      region. First, the navigation problem is considered as the optimization problem.
      Second, the environmental monitoring operator is introduced, to determine whether
      the algorithm falls into the geomagnetic anomaly region. Then, the behavior
      constraint operator is employed to get out of the abnormal region. Finally, the
      termination condition is triggered. Compared to the state-of- the-art, the
      proposed approach effectively overcomes the disturbance of the geomagnetic
      abnormal. The simulation result demonstrates the reliability and feasibility of
      the proposed approach in complex environments.

PMID- 28747885
TI  - Effects of Aging Stereotype Threat on Working Self-Concepts: An Event-Related
      Potentials Approach.
AB  - Although the influence of stereotype threat (ST) on working self-concepts has
      been highlighted in recent years, its neural underpinnings are unclear. Notably,
      the aging ST, which largely influences older adults' cognitive ability, mental
      and physical health, did not receive much attention. In order to investigate
      these issues, electroencephalogram (EEG) data were obtained from older adults
      during a modified Stroop task using neutral words, positive and negative self
      concept words in aging ST vs. neutral control conditions. Results showed longer
      reaction times (RTs) for identifying colors of words under the aging ST compared
      to the neutral condition. More importantly, the negative self-concept elicited
      more positive late P300 amplitudes and enhanced theta band activities compared to
      the positive self-concept or neutral words under the aging ST condition, whereas
      no difference was found between these self-concepts and neutral words in the
      control condition. Furthermore, the aging ST induced smaller theta band
      synchronization and enhanced alpha band synchronization compared to the control
      condition. Moreover, we also observed valence differences in self-concepts where
      the negative self-concept words reduced early P150/N170 complex relative to
      neutral words. These findings suggest that priming ST could activate negative
      self-concepts as current working self-concept, and that this influence occurred
      during a late neural time course.

PMID- 28747886
TI  - In-vitro Thermal Maps to Characterize Human Dental Enamel and Dentin.
AB  - The crown of a human tooth has an outer layer of highly-mineralized tissue called
      enamel, beneath which is dentin, a less-mineralized tissue which forms the bulk
      of the tooth-crown and root. The composition and structure of enamel and dentin
      are different, resulting in different thermal properties. This gives an
      opportunity to characterize enamel and dentin from their thermal properties and
      to visually present the findings as a thermal map. The thermal properties of
      demineralized enamel and dentin may also be sufficiently different from sound
      tissue to be seen on a thermal map, underpinning future thermal assessment of
      caries. The primary aim of this novel study was to produce a thermal map of a
      sound, human tooth-slice to visually characterize enamel and dentin. The
      secondary aim was to map a human tooth-slice with demineralized enamel and dentin
      to consider future diagnostic potential of thermal maps for caries-detection. Two
      human slices of teeth, one sound and one demineralized from a natural carious
      lesion, were cooled on ice, then transferred to a hotplate at 30 degrees C where
      the rewarming-sequence was captured by an infra-red thermal camera. Calculation
      of thermal diffusivity and thermal conductivity was undertaken, and two methods
      of data-processing used customized software to produce thermal maps from the
      thermal characteristic-time-to-relaxation and heat-exchange. The two types of
      thermal maps characterized enamel and dentin. In addition, sound and
      demineralized enamel and dentin were distinguishable within both maps. This
      supports thermal assessment of caries and requires further investigation on a
      whole tooth.

PMID- 28747887
TI  - Nutrient Sensing: Another Chemosensitivity of the Olfactory System.
AB  - Olfaction is a major sensory modality involved in real time perception of the
      chemical composition of the external environment. Olfaction favors anticipation
      and rapid adaptation of behavioral responses necessary for animal survival.
      Furthermore, recent studies have demonstrated that there is a direct action of
      metabolic peptides on the olfactory network. Orexigenic peptides such as ghrelin
      and orexin increase olfactory sensitivity, which in turn, is decreased by
      anorexigenic hormones such as insulin and leptin. In addition to peptides,
      nutrients can play a key role on neuronal activity. Very little is known about
      nutrient sensing in olfactory areas. Nutrients, such as carbohydrates, amino
      acids, and lipids, could play a key role in modulating olfactory sensitivity to
      adjust feeding behavior according to metabolic need. Here we summarize recent
      findings on nutrient-sensing neurons in olfactory areas and delineate the limits
      of our knowledge on this topic. The present review opens new lines of
      investigations on the relationship between olfaction and food intake, which could
      contribute to determining the etiology of metabolic disorders.

PMID- 28747889
TI  - Distribution of Silicified Microstructures, Regulation of Cinnamyl Alcohol
      Dehydrogenase and Lodging Resistance in Silicon and Paclobutrazol Mediated Oryza
      sativa.
AB  - Lodging is a phenomenon that affects most of the cereal crops including rice,
      Oryza sativa. This is due to the fragile nature of herbaceous plants whose stems
      are non-woody, thus affecting its ability to grow upright. Silicon (Si), a
      beneficial nutrient is often used to toughen and protect plants from biotic and
      abiotic stresses. Deposition of Si in plant tissues enhances the rigidity and
      stiffness of the plant as a whole. Silicified cells provide the much needed
      strength to the culm to resist breaking. Lignin plays important roles in cell
      wall structural integrity, stem strength, transport, mechanical support, and
      plant pathogen defense. The aim of this study is to resolve effects of Si on
      formation of microstructure and regulation of cinnamyl alcohol dehydrogenase
      (CAD), a key gene responsible for lignin biosynthesis. Besides evaluating
      silicon, paclobutrazol (PBZ) a plant growth retartdant that reduces internode
      elongation is also incorporated in this study. Hardness, brittleness and
      stiffness were improved in presence of silicon thus reducing lodging. Scanning
      electron micrographs with the aid of energy dispersive x-ray (EDX) was used to
      map silicon distribution. Presence of trichomes, silica cells, and silica bodies
      were detected in silicon treated plants. Transcripts of CAD gene was also
      upregulated in these plants. Besides, phloroglucinol staining showed presence of
      lignified vascular bundles and sclerenchyma band. In conclusion, silicon treated
      rice plants showed an increase in lignin content, silicon content, and formation
      of silicified microstructures.

PMID- 28747888
TI  - The Hsp72 and Hsp90alpha mRNA Responses to Hot Downhill Running Are Reduced
      Following a Prior Bout of Hot Downhill Running, and Occur Concurrently within
      Leukocytes and the Vastus Lateralis.
AB  - The leukocyte heat shock response (HSR) is used to determine individual's
      thermotolerance. The HSR and thermotolerance are enhanced following interventions
      such as preconditioning and/or acclimation/acclimatization. However, it is
      unclear whether the leukocyte HSR is an appropriate surrogate for the HSR in
      other tissues implicated within the pathophysiology of exertional heat illnesses
      (e.g., skeletal muscle), and whether an acute preconditioning strategy (e.g.,
      downhill running) can improve subsequent thermotolerance. Physically active, non
      heat acclimated participants were split into two groups to investigate the
      benefits of hot downhill running as preconditioning strategy. A hot
      preconditioning group (HPC; n = 6) completed two trials (HPC1HOTDOWN and
      HPC2HOTDOWN) of 30 min running at lactate threshold (LT) on -10% gradient in 30
      degrees C and 50% relative humidity (RH) separated by 7 d. A temperate
      preconditioning group (TPC; n = 5) completed 30 min running at LT on a -1%
      gradient in 20 degrees C and 50% (TPC1TEMPFLAT) and 7 d later completed 30 min
      running at LT on -10% gradient in 30 degrees C and 50% RH (TPC2HOTDOWN). Venous
      blood samples and muscle biopsies (vastus lateralis; VL) were obtained before,
      immediately after, 3, 24, and 48 h after each trial. Leukocyte and VL Hsp72,
      Hsp90alpha, and Grp78 mRNA relative expression was determined via RT-QPCR.
      Attenuated leukocyte and VL Hsp72 (2.8 to 1.8 fold and 5.9 to 2.4 fold; p < 0.05)
      and Hsp90alpha mRNA (2.9 to 2.4 fold and 5.2 to 2.4 fold; p < 0.05) responses
      accompanied reductions (p < 0.05) in physiological strain [exercising rectal
      temperature (-0.3 degrees C) and perceived muscle soreness (~ -14%)] during
      HPC2HOTDOWN compared to HPC1HOTDOWN (i.e., a preconditioning effect). Both VL and
      leukocyte Hsp72 and Hsp90alpha mRNA increased (p < 0.05) simultaneously following
      downhill runs and demonstrated a strong relationship (p < 0.01) of similar
      magnitudes with one another. Hot downhill running is an effective preconditioning
      strategy which ameliorates physiological strain, soreness and Hsp72 and
      Hsp90alpha mRNA responses to a subsequent bout. Leukocyte and VL analyses are
      appropriate tissues to infer the extent to which the HSR has been augmented.

PMID- 28747890
TI  - Longitudinal Associations of Leptin and Adiponectin with Heart Rate Variability
      in Children.
AB  - For early prevention of cardiovascular disease, early detection and risk factor
      insights are necessary. The autonomic balance reflects cardiovascular risk and
      can be measured by heart rate variability (HRV). Therefore, our purpose is to
      examine associations between HRV and the energy-related biomarkers leptin and
      adiponectin in children. Participants of this study were Belgian children
      recruited for the longitudinal ChiBS study (year 2010-2012). HRV was measured and
      fasting blood samples were taken in 249 children at baseline (4.4-11.0 y) and 223
      children at follow-up (6.7-12.2 y). Cross-sectional and longitudinal linear
      regression analyses were separated by sex and adjusted for age, socio-economic
      status, body fat%, negative emotions, puberty, and mean heart rate. Leptin was a
      negative cross-sectional and longitudinal predictor of parasympathetic activity
      in boys; while leptin in girls was cross-sectionally associated with higher LF
      and LF/HF suggesting sympathetic predominance. Adiponectin was a negative cross
      sectional and longitudinal predictor of parasympathetic activity in boys; but
      when adjusting for mean heart rate, this effect disappeared and adiponectin was a
      positive cross-sectional and longitudinal predictor of parasympathetic activity
      in girls. These results stress the importance of considering sex differences and
      adjustment for heart rate in testing HRV predictors. Leptin seemed
      disadvantageous for the autonomic balance, while adiponectin seemed advantageous
      for the autonomic balance in girls only. More research is needed to see whether
      leptin and adiponectin are interesting in cardiovascular screening/prevention or
      in determining the cardiovascular gain during weight loss follow-up.

PMID- 28747891
TI  - Proliferative Role of Kv11 Channels in Murine Arteries.
AB  - K+ channels encoded by the ether-a-go-go related gene (ERG1 or KCNH2) are
      important determinants of the cardiac action potential. Expression of both
      cardiac isoforms (ERG1a and ERG1b) were identified in murine portal vein and
      distinctive voltage-gated K+ currents were recorded from single myocytes. The aim
      of the present study was to ascertain the expression and functional impact of ERG
      channels in murine arteries. Methods: Quantitative RT-PCR was undertaken on RNA
      extracted from a number of murine arteries. Immunofluorescence was performed on
      single vascular smooth muscle cells using antibodies against the ERG1 expression
      product (Kv11.1). Single cell electrophysiology was performed on myocytes from
      portal vein and several different arteries, complimented by isometric tension
      recordings. Proliferation assays were undertaken on smooth muscle cells isolated
      from femoral arteries. Results: ERG1 transcripts were detected in all murine
      blood vessels, and Kv11.1 immunofluorescence was observed in all smooth muscle
      cells. However, K+ currents with properties consistent with ERG channels were
      only recorded in portal vein myocytes. Moreover, ERG channel blockers (E4031 or
      dofetilide, 1 MUM) failed to depolarize carotid arteries or produce contraction.
      Proliferation of arterial smooth muscle cells was associated with a marked
      increase in ERG1 expression and ERG blockers suppressed proliferation
      significantly. Conclusions: These data reveal that arterial blood vessels express
      ERG channels that appear to be functional silent in contractile smooth muscle but
      contribute to proliferative response.

PMID- 28747892
TI  - How Useful Is Electroencephalography in the Diagnosis of Autism Spectrum
      Disorders and the Delineation of Subtypes: A Systematic Review.
AB  - Autism spectrum disorders (ASD) are thought to be associated with abnormal neural
      connectivity. Presently, neural connectivity is a theoretical construct that
      cannot be easily measured. Research in network science and time series analysis
      suggests that neural network structure, a marker of neural activity, can be
      measured with electroencephalography (EEG). EEG can be quantified by different
      methods of analysis to potentially detect brain abnormalities. The aim of this
      review is to examine evidence for the utility of three methods of EEG signal
      analysis in the ASD diagnosis and subtype delineation. We conducted a review of
      literature in which 40 studies were identified and classified according to the
      principal method of EEG analysis in three categories: functional connectivity
      analysis, spectral power analysis, and information dynamics. All studies
      identified significant differences between ASD patients and non-ASD subjects.
      However, due to high heterogeneity in the results, generalizations could not be
      inferred and none of the methods alone are currently useful as a new diagnostic
      tool. The lack of studies prevented the analysis of these methods as tools for
      ASD subtypes delineation. These results confirm EEG abnormalities in ASD, but as
      yet not sufficient to help in the diagnosis. Future research with larger samples
      and more robust study designs could allow for higher sensitivity and consistency
      in characterizing ASD, paving the way for developing new means of diagnosis.

PMID- 28747893
TI  - The Indecision Model of Psychophysical Performance in Dual-Presentation Tasks:
      Parameter Estimation and Comparative Analysis of Response Formats.
AB  - Psychophysical data from dual-presentation tasks are often collected with the two
      alternative forced-choice (2AFC) response format, asking observers to guess when
      uncertain. For an analytical description of performance, psychometric functions
      are then fitted to data aggregated across the two orders/positions in which
      stimuli were presented. Yet, order effects make aggregated data uninterpretable,
      and the bias with which observers guess when uncertain precludes separating
      sensory from decisional components of performance. A ternary response format in
      which observers are also allowed to report indecision should fix these problems,
      but a comparative analysis with the 2AFC format has never been conducted. In
      addition, fitting ternary data separated by presentation order poses serious
      challenges. To address these issues, we extended the indecision model of
      psychophysical performance to accommodate the ternary, 2AFC, and same-different
      response formats in detection and discrimination tasks. Relevant issues for
      parameter estimation are also discussed along with simulation results that
      document the superiority of the ternary format. These advantages are demonstrated
      by fitting the indecision model to published detection and discrimination data
      collected with the ternary, 2AFC, or same-different formats, which had been
      analyzed differently in the sources. These examples also show that 2AFC data are
      unsuitable for testing certain types of hypotheses. matlab and R routines written
      for our purposes are available as Supplementary Material, which should help
      spread the use of the ternary format for dependable collection and interpretation
      of psychophysical data.

PMID- 28747894
TI  - Dimensions Underlying the Perceived Similarity of Acoustic Environments.
AB  - Scientific research on how people perceive or experience and/or understand the
      acoustic environment as a whole (i.e., soundscape) is still in development. In
      order to predict how people would perceive an acoustic environment, it is central
      to identify its underlying acoustic properties. This was the purpose of the
      present study. Three successive experiments were conducted. With the aid of 30
      university students, the first experiment mapped the underlying dimensions of
      perceived similarity among 50 acoustic environments, using a visual sorting task
      of their spectrograms. Three dimensions were identified: (1) Distinguishable
      Indistinguishable sound sources, (2) Background-Foreground sounds, and (3)
      Intrusive-Smooth sound sources. The second experiment was aimed to validate the
      results from Experiment 1 by a listening experiment. However, a majority of the
      10 expert listeners involved in Experiment 2 used a qualitatively different
      approach than the 30 university students in Experiment 1. A third experiment was
      conducted in which 10 more expert listeners performed the same task as per
      Experiment 2, with spliced audio signals. Nevertheless, Experiment 3 provided a
      statistically significantly worse result than Experiment 2. These results suggest
      that information about the meaning of the recorded sounds could be retrieved in
      the spectrograms, and that the meaning of the sounds may be captured with the aid
      of holistic features of the acoustic environment, but such features are still
      unexplored and further in-depth research is needed in this field.

PMID- 28747895
TI  - Combining Standard Conventional Measures and Ecological Momentary Assessment of
      Depression, Anxiety and Coping Using Smartphone Application in Minor Stroke
      Population: A Longitudinal Study Protocol.
AB  - Context: Stroke has several consequences on survivors' daily life even for those
      who experience short-lasting neurological symptoms with no functional disability.
      Depression and anxiety are common psychological disorders occurring after a
      stroke. They affect long-term outcomes and quality of life but they are difficult
      to diagnose because of the neurobiological consequences of brain lesions. Current
      research priority is given to the improvement of the detection and prevention of
      those post-stroke psychological disorders. Although previous studies have brought
      promising perspectives, their designs based on retrospective tools involve some
      limits regarding their ecological validity. Ecological Momentary Assessment (EMA)
      is an alternative to conventional instruments that could be a key in research for
      understanding processes that underlined post-stroke depression and anxiety onset.
      We aim to evaluate the feasibility and validity of anxiety, depression and coping
      EMA for minor stroke patients. Methods: Patients hospitalized in an Intensive
      Neuro-vascular Care Unit between April 2016 and January 2017 for a minor stroke
      is involved in a study based on an EMA methodology. We use a smartphone
      application in order to assess anxiety and depression symptoms and coping
      strategies four times a day during 1 week at three different times after stroke
      (hospital discharge, 2 and 4 months). Participants' self-reports and clinician
      rates of anxiety, depression and coping are collected simultaneously using
      conventional and standard instruments. Feasibility of the EMA method will be
      assessed considering the participation and compliance rate. Validity will be the
      assessed by comparing EMA and conventional self-report and clinician-rated
      measures. Discussion: We expect this study to contribute to the development of
      EMA using smartphone in minor stroke population. EMA method offers promising
      research perspective in the assessment and understanding of post-stroke
      psychological disorders. The development of EMA in stroke population could lead
      to clinical implications such as remotely psychological follow-ups during early
      supported discharge. Trial registration: European Clinical Trials Database Number
      2014-A01937-40.

PMID- 28747896
TI  - Time-Dependent Effects of Acute Exercise on University Students' Cognitive
      Performance in Temperate and Cold Environments.
AB  - Background: Few studies have examined the acute exercise-induced changes in
      cognitive performance in different thermal environments and the time course
      effects. Objective: Investigate the time-dependent effects of acute exercise on
      university students' processing speed, working memory and cognitive flexibility
      in temperate and cold environments. Method: Twenty male university students (age
      23.5 +/- 2.0 years) with moderate physical activity level participated in a
      repeated-measures within-subjects design. Processing speed, working memory and
      cognitive flexibility were assessed using CogState test battery at baseline
      (BASE), followed by a 45-min rest (REST), immediately after (EX) and 30 min after
      (POST-EX) 30-min moderate-intensity treadmill running in both temperate (TEMP; 25
      degrees C) and cold (COLD; 10 degrees C) environments. Mean skin temperature
      (MST) and thermal sensation (TS) were also recorded. Two-way repeated measures
      ANOVA was performed to analyze each variable. Spearman's rho was used to identify
      the correlations between MST, TS and cognitive performance. Results: Reaction
      time (RT) of processing speed and working memory decreased immediately after
      exercise in both conditions (processing speed: p = 0.003; working memory: p =
      0.007). The facilitating effects on processing speed disappeared within 30 min
      after exercise in TEMP (p = 0.163) and COLD (p = 0.667), while improvements on
      working memory remained 30 min after exercise in TEMP (p = 0.047), but not in
      COLD (p = 0.663). Though RT of cognitive flexibility reduced in both conditions
      (p = 0.003), no significance was found between EX and REST (p = 0.135). Increased
      MST and TS were significantly associated with reductions in processing speed RT
      (MST: r = -0.341, p < 0.001; TS: r = -0.262, p = 0.001) and working memory RT
      (MST: r = -0.282, p < 0.001; TS: r = -0.2229, p = 0.005), and improvements in
      working memory accuracy (MST: r = 0.249, p = 0.002; TS: r = 0.255, p = 0.001).
      Conclusion: The results demonstrate different time-dependent effects of acute
      exercise on cognition in TEMP and COLD. Our study reveals facilitating effects of
      exercise on university students' processing speed and working memory in both
      environments. However, in contrast to TEMP, effects on working memory in COLD are
      transient.

PMID- 28747897
TI  - Identification of Emerging Human Mastitis Pathogens by MALDI-TOF and Assessment
      of Their Antibiotic Resistance Patterns.
AB  - Lactational mastitis constitutes one of the main causes of undesired weaning,
      depriving the mother-infant pair from the benefits of breastfeeding; therefore,
      this condition should be considered a relevant public health issue. The role of
      specific microorganisms remains unclear since human milk cultures and antibiotic
      susceptibility testing (AST) are not routinely performed, despite the fact that
      this would be key to ensure an early and effective diagnosis and treatment. The
      objective of this study was to describe the culturable microbial diversity in 647
      milk samples from breastfeeding women with clinical symptoms of mastitis by
      Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry
      (MALDI-TOF) VITEK MS technology and to analyze the antimicrobial susceptibility
      profiles of a collection of isolates from these samples by the VITEK 2 AST
      system. Staphylococcus epidermidis was the most common species isolated from
      mastitis samples (87.6%), while Staphylococcus aureus was detected in 22.1%.
      Streptococci constituted the second (68.6%) most prevalent bacterial group, with
      Streptococcus mitis/oralis, Streptococcus salivarius, and Streptococcus
      parasanguinis detected with frequencies of 40.8, 36.8, and 14.4%, respectively.
      The antibiotic susceptibility profiles of 642 staphylococcal isolates indicated a
      remarkable resistance to benzylpenicillin (88.3%) and erythromycin (67.3%) with
      differences between species. A high percentage of Staphylococcus isolates were
      resistant to at least one antibiotic (Staphylococcus hominis, 100%; S.
      epidermidis, 98.2%; S. aureus, 92.9%; Staphylococcus lugdunensis, 90.5%) and the
      percentage of multidrug-resistance (MDR) isolates was noticeable (S. hominis,
      81%; S. epidermidis, 64.4%; S. aureus, 11.5%; S. lugdunensis, 10.5%). In relation
      to streptococcal isolates (n = 524), AST revealed high or moderate percentages of
      resistance to erythromycin (68.7%), benzylpenicillin (63.7%), ampicillin (51.5%),
      and tetracycline (30.8%). Antibiotic resistance to at least one antibiotic was
      detected in 97.6% of S. parasanguinis, 92.6% of S. salivarius, 83.3% of S.
      mitis/oralis, and 72.4% of Streptococcus vestibularis isolates. A significant
      number of MDR streptococcal isolates was also found (S. parasanguinis, 51.2%; S.
      salivarius, 39.3%; S. mitis/oralis, 34.6%; and S. vestibularis, 19%). The results
      highlight the important role of coagulase-negative staphylococci and streptococci
      as human mastitis-causing agents. Moreover, the high rates of antimicrobial
      resistance among these microorganisms must be contemplated as an issue of
      clinical relevance in relation to treatment options.

PMID- 28747898
TI  - Piriformospora indica Reprograms Gene Expression in Arabidopsis Phosphate
      Metabolism Mutants But Does Not Compensate for Phosphate Limitation.
AB  - Piriformospora indica is an endophytic fungus of Sebacinaceae which colonizes the
      roots of many plant species and confers benefits to the hosts. We demonstrate
      that approximately 75% of the genes, which respond to P. indica in Arabidopsis
      roots, differ among seedlings grown on normal phosphate (Pi) or Pi limitation
      conditions, and among wild-type and the wrky6 mutant impaired in the regulation
      of the Pi metabolism. Mapman analyses suggest that the fungus activates different
      signaling, transport, metabolic and developmental programs in the roots of wild
      type and wrky6 seedlings under normal and low Pi conditions. Under low Pi, P.
      indica promotes growth and Pi uptake of wild-type seedlings, and the stimulatory
      effects are identical for mutants impaired in the PHOSPHATE TRANSPORTERS1;1, -1;2
      and -1;4. The data suggest that the fungus does not stimulate Pi uptake, but
      adapts the expression profiles to Pi limitation in Pi metabolism mutants.

PMID- 28747899
TI  - The Global Redox Responding RegB/RegA Signal Transduction System Regulates the
      Genes Involved in Ferrous Iron and Inorganic Sulfur Compound Oxidation of the
      Acidophilic Acidithiobacillus ferrooxidans.
AB  - The chemical attack of ore by ferric iron and/or sulfuric acid releases valuable
      metals. The products of these reactions are recycled by iron and sulfur oxidizing
      microorganisms. These acidophilic chemolithotrophic prokaryotes, among which
      Acidithiobacillus ferrooxidans, grow at the expense of the energy released from
      the oxidation of ferrous iron and/or inorganic sulfur compounds (ISCs). In At.
      ferrooxidans, it has been shown that the expression of the genes encoding the
      proteins involved in these respiratory pathways is dependent on the electron
      donor and that the genes involved in iron oxidation are expressed before those
      responsible for ISCs oxidation when both iron and sulfur are present. Since the
      redox potential increases during iron oxidation but remains stable during sulfur
      oxidation, we have put forward the hypothesis that the global redox responding
      two components system RegB/RegA is involved in this regulation. To understand the
      mechanism of this system and its role in the regulation of the aerobic
      respiratory pathways in At. ferrooxidans, the binding of different forms of RegA
      (DNA binding domain, wild-type, unphosphorylated and phosphorylated-like forms of
      RegA) on the regulatory region of different genes/operons involved in ferrous
      iron and ISC oxidation has been analyzed. We have shown that the four RegA forms
      are able to bind specifically the upstream region of these genes. Interestingly,
      the phosphorylation of RegA did not change its affinity for its cognate DNA. The
      transcriptional start site of these genes/operons has been determined. In most
      cases, the RegA binding site(s) was (were) located upstream from the -35 (or -24)
      box suggesting that RegA does not interfere with the RNA polymerase binding.
      Based on the results presented in this report, the role of the RegB/RegA system
      in the regulation of the ferrous iron and ISC oxidation pathways in At.
      ferrooxidans is discussed.

PMID- 28747900
TI  - Fungal and Bacterial Diversity Isolated from Aquilaria malaccensis Tree and Soil,
      Induces Agarospirol Formation within 3 Months after Artificial Infection.
AB  - Aquilaria malaccensis Lam, commonly known as Agarwood, is a highly valuable
      species used in production of agar oil from its infected wood, which is utilized
      in pharmaceutical and perfumery industry. Agar oil formation in agarwood takes
      years through the natural process which is induced by natural or artificial
      injury or microbial infection. The role of soil fungi and bacteria in artificial
      induction is still an unexplored area. In the present study, we isolated the
      fungal and bacterial community residing inside the stem of A. malaccensis tree
      and circumventing soil, samples collected from 21 different sites of the north
      eastern state Assam of India and explored their potential in induction of
      Agarospirol (2-(6,10-Dimethylspiro[4,5]dec-6-en-2-yl)-2-propanol) production by
      artificially infecting the trees with these microorganisms. A total 340 fungi and
      131 bacteria were isolated from 50 stem samples, and 188 fungi and 148 bacteria
      were isolated from 50 soil samples. Highest Shannon (H' = 2.43) and Fisher (alpha
      = 5.57) diversity index was observed in the stem isolates. The dominant fungal
      genus was Trichoderma in stem with Pi value of 0.18; while in soil, Aspergillus
      showed dominance with Pi value 0.73. In bacteria, Bacillus genera showed
      dominance in both stem and soil samples with Pi = 0.62 and 0.51, respectively.
      Forty fungal and bacterial isolates were used to assess their potential to induce
      formation of agarwood in A. malaccensis by artificial infection method. Gas
      chromatography mass spectroscopy (GC-MS) analysis confirmed development of
      Agarwood by the presence of Agarospirol compound in samples collected after 3
      months of the artificial infection. Only 31% of bacterial and 23% of fungal
      isolates showed their ability in production of Agarospirol by artificial
      infection method. Bacteria Pantoea dispersa and fungi Penicillium polonicum
      showed the highest production in comparison to other isolates.

PMID- 28747901
TI  - Could the Recent Zika Epidemic Have Been Predicted?
AB  - Given knowledge at the time, the recent 2015-2016 zika virus (ZIKV) epidemic
      probably could not have been predicted. Without the prior knowledge of ZIKV being
      already present in South America, and given the lack of understanding of key
      epidemiologic processes and long-term records of ZIKV cases in the continent, the
      best related prediction could be carried out for the potential risk of a generic
      Aedes-borne disease epidemic. Here we use a recently published two-vector basic
      reproduction number model to assess the predictability of the conditions
      conducive to epidemics of diseases like zika, chikungunya, or dengue, transmitted
      by the independent or concurrent presence of Aedes aegypti and Aedes albopictus.
      We compare the potential risk of transmission forcing the model with the observed
      climate and with state-of-the-art operational forecasts from the North American
      Multi Model Ensemble (NMME), finding that the predictive skill of this new
      seasonal forecast system is highest for multiple countries in Latin America and
      the Caribbean during the December-February and March-May seasons, and slightly
      lower-but still of potential use to decision-makers-for the rest of the year. In
      particular, we find that above-normal suitable conditions for the occurrence of
      the zika epidemic at the beginning of 2015 could have been successfully predicted
      at least 1 month in advance for several zika hotspots, and in particular for
      Northeast Brazil: the heart of the epidemic. Nonetheless, the initiation and
      spread of an epidemic depends on the effect of multiple factors beyond climate
      conditions, and thus this type of approach must be considered as a guide and not
      as a formal predictive tool of vector-borne epidemics.

PMID- 28747902
TI  - In-silico Taxonomic Classification of 373 Genomes Reveals Species
      Misidentification and New Genospecies within the Genus Pseudomonas.
AB  - The genus Pseudomonas has one of the largest diversity of species within the
      Bacteria kingdom. To date, its taxonomy is still being revised and updated. Due
      to the non-standardized procedure and ambiguous thresholds at species level,
      largely based on 16S rRNA gene or conventional biochemical assay, species
      identification of publicly available Pseudomonas genomes remains questionable. In
      this study, we performed a large-scale analysis of all Pseudomonas genomes with
      species designation (excluding the well-defined P. aeruginosa) and re-evaluated
      their taxonomic assignment via in silico genome-genome hybridization and/or
      genetic comparison with valid type species. Three-hundred and seventy-three
      pseudomonad genomes were analyzed and subsequently clustered into 145 distinct
      genospecies. We detected 207 erroneous labels and corrected 43 to the proper
      species based on Average Nucleotide Identity Multilocus Sequence Typing (MLST)
      sequence similarity to the type strain. Surprisingly, more than half of the
      genomes initially designated as Pseudomonas syringae and Pseudomonas fluorescens
      should be classified either to a previously described species or to a new
      genospecies. Notably, high pairwise average nucleotide identity (>95%) indicating
      species-level similarity was observed between P. synxantha-P. libanensis, P.
      psychrotolerans-P. oryzihabitans, and P. kilonensis- P. brassicacearum, that were
      previously differentiated based on conventional biochemical tests and/or genome
      genome hybridization techniques.

PMID- 28747903
TI  - Stoichiometric Mismatch between Consumers and Resources Mediates the Growth of
      Rocky Intertidal Suspension Feeders.
AB  - The concept of ecological stoichiometry-the balancing of elemental ratios in
      ecological interactions-has transformed our thinking about processes in natural
      systems. Here, this perspective is applied to rocky shore ecosystems to explore
      the consequences of variation in internal nutrient ratios across two trophic
      levels. Specifically, I measured the internal concentrations of carbon (C) and
      nitrogen (N) in mussels (Mytilus spp.) and particulate organic matter (POM) to
      evaluate the effects of stoichiometric mismatch-the difference in the carbon-to
      nitrogen ratio (C:N) between a consumer and its resources-on mussel growth at
      sites on the coasts of Oregon, USA, and the South Island of New Zealand. As POM
      quality (i.e., Chl a, a proxy for phytoplankton availability in the POM)
      increased, C:N of the POM declined, but C:N of mussels increased. This resulted
      in a greater mismatch in C:N between mussels and their food source at low Chl a.
      Mussel growth across sites was positively associated with Chl a, particulate
      organic carbon (POC), and particulate organic nitrogen (PON) but negatively
      associated with stoichiometric mismatch. Overall, as the elemental ratios of
      consumers became more different from those of their resources, growth declined,
      likely due to the energetic cost associated with processing lower quality food.
      Furthermore, the effect of food quantity on growth depended on stoichiometric
      mismatch. In New Zealand, where mismatch was high-i.e., consumer C:N differed
      substantially from resource C:N-consumer growth was strongly affected by resource
      quantity (Chl a or POC). However, in Oregon, where mismatch was low, the
      relationship between resource quantity and growth was considerably weaker. This
      interaction between resource quantity and mismatch was not apparent for PON,
      which is consistent with variation in PON underlying variation in POM C:N and
      highlights the role of N in limiting growth. Previous research has neglected the
      importance of ecological stoichiometry as a mediator of consumer-resource
      interactions in rocky intertidal communities. I show that resource quality and
      quantity interact to determine consumer growth, highlighting the utility of
      ecological stoichiometry in understanding spatial subsidies in benthic marine
      systems.

PMID- 28747904
TI  - Bridging Food Webs, Ecosystem Metabolism, and Biogeochemistry Using Ecological
      Stoichiometry Theory.
AB  - Although aquatic ecologists and biogeochemists are well aware of the crucial
      importance of ecosystem functions, i.e., how biota drive biogeochemical processes
      and vice-versa, linking these fields in conceptual models is still uncommon.
      Attempts to explain the variability in elemental cycling consequently miss an
      important biological component and thereby impede a comprehensive understanding
      of the underlying processes governing energy and matter flow and transformation.
      The fate of multiple chemical elements in ecosystems is strongly linked by biotic
      demand and uptake; thus, considering elemental stoichiometry is important for
      both biogeochemical and ecological research. Nonetheless, assessments of
      ecological stoichiometry (ES) often focus on the elemental content of biota
      rather than taking a more holistic view by examining both elemental pools and
      fluxes (e.g., organismal stoichiometry and ecosystem process rates). ES theory
      holds the promise to be a unifying concept to link across hierarchical scales of
      patterns and processes in ecology, but this has not been fully achieved.
      Therefore, we propose connecting the expertise of aquatic ecologists and
      biogeochemists with ES theory as a common currency to connect food webs,
      ecosystem metabolism, and biogeochemistry, as they are inherently concatenated by
      the transfer of carbon, nitrogen, and phosphorous through biotic and abiotic
      nutrient transformation and fluxes. Several new studies exist that demonstrate
      the connections between food web ecology, biogeochemistry, and ecosystem
      metabolism. In addition to a general introduction into the topic, this paper
      presents examples of how these fields can be combined with a focus on ES. In this
      review, a series of concepts have guided the discussion: (1) changing
      biogeochemistry affects trophic interactions and ecosystem processes by altering
      the elemental ratios of key species and assemblages; (2) changing trophic
      dynamics influences the transformation and fluxes of matter across environmental
      boundaries; (3) changing ecosystem metabolism will alter the chemical diversity
      of the non-living environment. Finally, we propose that using ES to link nutrient
      cycling, trophic dynamics, and ecosystem metabolism would allow for a more
      holistic understanding of ecosystem functions in a changing environment.

PMID- 28747905
TI  - From Ecological Stoichiometry to Biochemical Composition: Variation in N and P
      Supply Alters Key Biosynthetic Rates in Marine Phytoplankton.
AB  - One of the major challenges in ecological stoichiometry is to establish how
      environmental changes in resource availability may affect both the biochemical
      composition of organisms and the species composition of communities. This is a
      pressing issue in many coastal waters, where anthropogenic activities have caused
      large changes in riverine nutrient inputs. Here we investigate variation in the
      biochemical composition and synthesis of amino acids, fatty acids (FA), and
      carbohydrates in mixed phytoplankton communities sampled from the North Sea. The
      communities were cultured in chemostats supplied with different concentrations of
      dissolved inorganic nitrogen (DIN) and phosphorus (DIP) to establish four
      different types of resource limitations. Diatoms dominated under N-limited, N+P
      limited and P-limited conditions. Cyanobacteria became dominant in one of the N
      limited chemostats and green algae dominated in the one P-limited chemostat and
      under light-limited conditions. Changes in nutrient availability directly
      affected amino acid content, which was lowest under N and N+P limitation, higher
      under P-limitation and highest when light was the limiting factor. Storage
      carbohydrate content showed the opposite trend and storage FA content seemed to
      be co-dependent on community composition. The synthesis of essential amino acids
      was affected under N and N+P limitation, as the transformation from non-essential
      to essential amino acids decreased at DIN:DIP <= 6. The simple community
      structure and clearly identifiable nutrient limitations confirm and clarify
      previous field findings in the North Sea. Our results show that different
      phytoplankton groups are capable of adapting their key biosynthetic rates and
      hence their biochemical composition to different degrees when experiencing shifts
      in nutrient availability. This will have implications for phytoplankton growth,
      community structure, and the nutritional quality of phytoplankton as food for
      higher trophic levels.

PMID- 28747906
TI  - Characterization of Integrons and Resistance Genes in Salmonella Isolates from
      Farm Animals in Shandong Province, China.
AB  - A total of 154 non-duplicate Salmonella isolates were recovered from 1,105 rectal
      swabs collected from three large-scale chicken farms (78/325, 24.0%), three large
      scale duck farms (56/600, 9.3%) and three large-scale pig farms (20/180, 11.1%)
      between April and July 2016. Seven serotypes were identified among the 154
      isolates, with the most common serotype in chickens and ducks being Salmonella
      enteritidis and in pigs Salmonella typhimurium. Antimicrobial susceptibility
      testing revealed that high antimicrobial resistance rates were observed for
      tetracycline (72.0%) and ampicillin (69.4%) in all sources. Class 1 integrons
      were detected in 16.9% (26/154) of these isolates and contained gene cassettes
      aadA2, aadA1, drfA1-aadA1, drfA12-aadA2, and drfA17-aadA5. Three beta-lactamase
      genes were detected among the 154 isolates, and most of the isolates carried
      blaTEM-1(55/154), followed by blaPSE-1(14/154) and blaCTX-M-55 (11/154). Three
      plasmid-mediated quinolone resistance genes were detected among the 154 isolates,
      and most of the isolates carried qnrA (113/154), followed by qnrB (99/154) and
      qnrS (10/154). Fifty-four isolates carried floR among the 154 isolates.
      Multilocus sequence typing (MLST) analysis showed that nine sequence types (STs)
      were identified; ST11 was the most frequent genotype in chickens and ducks, and
      ST19 was identified in pigs. Our findings indicated that Salmonella was
      widespread, and the overuse of antibiotics in animals should be reduced
      considerably in developing countries.

PMID- 28747907
TI  - Membrane Phosphoproteomics of Yeast Early Response to Acetic Acid: Role of Hrk1
      Kinase and Lipid Biosynthetic Pathways, in Particular Sphingolipids.
AB  - Saccharomyces cerevisiae response and tolerance to acetic acid is critical in
      industrial biotechnology and in acidic food and beverages preservation. The HRK1
      gene, encoding a protein kinase of unknown function belonging to the "Npr1
      family" of kinases known to be involved in the regulation of plasma membrane
      transporters, is an important determinant of acetic acid tolerance. This study
      was performed to identify the alterations occurring in yeast membrane
      phosphoproteome profile during the adaptive early response to acetic acid stress
      (following 1 h of exposure to a sub-lethal inhibitory concentration; 50 mM at pH
      4.0) and the effect of HRK1 expression on the phosphoproteome. Results from mass
      spectrometry analysis following the prefractionation and specific enrichment of
      phosphorylated peptides using TiO2 beads highlight the contribution of processes
      related with translation, protein folding and processing, transport, and cellular
      homeostasis in yeast response to acetic acid stress, with particular relevance
      for changes in phosphorylation of transport-related proteins, found to be highly
      dependent on the Hrk1 kinase. Twenty different phosphoproteins known to be
      involved in lipid and sterol metabolism were found to be differently
      phosphorylated in response to acetic acid stress, including several
      phosphopeptides that had not previously been described as being phosphorylated.
      The suggested occurrence of cellular lipid composition remodeling during the
      short term yeast response to acetic acid was confirmed: Hrk1 kinase-independent
      reduction in phytoceramide levels and a reduction in phosphatidylcholine and
      phosphatidylinositol levels under acetic acid stress in the more susceptible
      hrk1Delta strain were revealed by a lipidomic analysis.

PMID- 28747908
TI  - Unraveling RubisCO Form I and Form II Regulation in an Uncultured Organism from a
      Deep-Sea Hydrothermal Vent via Metagenomic and Mutagenesis Studies.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) catalyzes the first
      major step of carbon fixation in the Calvin-Benson-Bassham (CBB) cycle. This
      autotrophic CO2 fixation cycle accounts for almost all the assimilated carbon on
      Earth. Due to the primary role that RubisCO plays in autotrophic carbon fixation,
      it is important to understand how its gene expression is regulated and the enzyme
      is activated. Since the majority of all microorganisms are currently not
      culturable, we used a metagenomic approach to identify genes and enzymes
      associated with RubisCO expression. The investigated metagenomic DNA fragment
      originates from the deep-sea hydrothermal vent field Nibelungen at 8 degrees 18'
      S along the Mid-Atlantic Ridge. It is 13,046 bp and resembles genes from
      Thiomicrospira crunogena. The fragment encodes nine open reading frames (ORFs)
      which include two types of RubisCO, form I (CbbL/S) and form II (CbbM), two LysR
      transcriptional regulators (LysR1 and LysR2), two von Willebrand factor type A
      (CbbO-m and CbbO-1), and two AAA+ ATPases (CbbQ-m and CbbQ-1), expected to
      function as RubisCO activating enzymes. In silico analyses uncovered several
      putative LysR binding sites and promoter structures. Functions of some of these
      DNA motifs were experimentally confirmed. For example, according to mobility
      shift assays LysR1's binding ability to the intergenic region of lysR1 and cbbL
      appears to be intensified when CbbL or LysR2 are present. Binding of LysR2
      upstream of cbbM appears to be intensified if CbbM is present. Our study suggests
      that CbbQ-m and CbbO-m activate CbbL and that LysR1 and LysR2 proteins promote
      CbbQ-m/CbbO-m expression. CbbO-1 seems to activate CbbM and CbbM itself appears
      to contribute to intensifying LysR's binding ability and thus its own
      transcriptional regulation. CbbM furthermore appears to impair cbbL expression. A
      model summarizes the findings and predicts putative interactions of the different
      proteins influencing RubisCO gene regulation and expression.

PMID- 28747909
TI  - The Physiological Functions and Structural Determinants of Catalytic Bias in the
      [FeFe]-Hydrogenases CpI and CpII of Clostridium pasteurianum Strain W5.
AB  - The first generation of biochemical studies of complex, iron-sulfur-cluster
      containing [FeFe]-hydrogenases and Mo-nitrogenase were carried out on enzymes
      purified from Clostridium pasteurianum (strain W5). Previous studies suggested
      that two distinct [FeFe]-hydrogenases are expressed differentially under nitrogen
      fixing and non-nitrogen-fixing conditions. As a result, the first characterized
      [FeFe]-hydrogenase (CpI) is presumed to have a primary role in central
      metabolism, recycling reduced electron carriers that accumulate during
      fermentation via proton reduction. A role for capturing reducing equivalents
      released as hydrogen during nitrogen fixation has been proposed for the second
      hydrogenase, CpII. Biochemical characterization of CpI and CpII indicated CpI has
      extremely high hydrogen production activity in comparison to CpII, while CpII has
      elevated hydrogen oxidation activity in comparison to CpI when assayed under the
      same conditions. This suggests that these enzymes have evolved a catalytic bias
      to support their respective physiological functions. Using the published genome
      of C. pasteurianum (strain W5) hydrogenase sequences were identified, including
      the already known [NiFe]-hydrogenase, CpI, and CpII sequences, and a third
      hydrogenase, CpIII was identified in the genome as well. Quantitative real-time
      PCR experiments were performed in order to analyze transcript abundance of the
      hydrogenases under diazotrophic and non-diazotrophic growth conditions. There is
      a markedly reduced level of CpI gene expression together with concomitant
      increases in CpII gene expression under nitrogen-fixing conditions. Structure
      based analyses of the CpI and CpII sequences reveal variations in their catalytic
      sites that may contribute to their alternative physiological roles. This work
      demonstrates that the physiological roles of CpI and CpII are to evolve and to
      consume hydrogen, respectively, in concurrence with their catalytic activities in
      vitro, with CpII capturing excess reducing equivalents under nitrogen fixation
      conditions. Comparison of the primary sequences of CpI and CpII and their
      homologs provides an initial basis for identifying key structural determinants
      that modulate hydrogen production and hydrogen oxidation activities.

PMID- 28747910
TI  - Natural Killer Cell-Based Cancer Immunotherapies: From Immune Evasion to
      Promising Targeted Cellular Therapies.
AB  - Immunotherapies based on natural killer (NK) cells are among the most promising
      therapies under development for the treatment of so far incurable forms of
      leukemia and other types of cancer. The importance of NK cells for the control of
      viral infections and cancer is supported among others by the findings that
      viruses and tumors use a multitude of mechanisms to subvert and evade the NK cell
      system. Infections and malignant diseases can further lead to the shaping of NK
      cell populations with altered reactivity. Counter measures of potential
      therapeutic impact include the blocking of inhibitory interactions between NK
      cell receptors and their cellular ligands, the enhancement of activating receptor
      signals, and the infusion of large numbers of ex vivo generated and selected NK
      cells. Moreover, the specific cross-linking of NK cells to their target cells
      using chimeric antigen receptors or therapeutic bi-/trispecific antibody reagents
      is a promising approach. In this context, NK cells stand out by their positive
      effects and safety demonstrated in most clinical trials so far. Based in part on
      results of the recent EC-sponsored project "NATURIMMUN" and considering
      additional published work in the field, we discuss below new developments and
      future directions that have the potential to further advance and establish NK
      cell-based therapies at the clinics on a broader scale.

PMID- 28747911
TI  - F1 Domain of the Leishmania (Leishmania) donovani Nucleoside Hydrolase Promotes a
      Th1 Response in Leishmania (Leishmania) infantum Cured Patients and in
      Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis.
AB  - The Leishmania (Leishmania) donovani nucleoside hydrolase NH36 is the main
      antigen of the Leishmune(r) vaccine and one of the promising candidates for
      vaccination against visceral leishmaniasis. The antigenicity of the N-terminal
      (F1), the central (F2), or the C-terminal recombinant domain (F3) of NH36 was
      evaluated using peripheral blood mononuclear cells (PBMC) from individuals
      infected with L. (L.) infantum from an endemic area of visceral leishmaniasis of
      Spain. Both NH36 and F1 domains significantly increased the PBMC proliferation
      stimulation index of cured patients and infected asymptomatic individuals
      compared to healthy controls. Moreover, F1 induced a 19% higher proliferative
      response than NH36 in asymptomatic exposed subjects. In addition, in patients
      cured from visceral leishmaniasis, proliferation in response to NH36 and F1 was
      accompanied by a significant increase of IFN-gamma and TNF-alpha secretion, which
      was 42-43% higher, in response to F1 than to NH36. The interleukin 17 (IL-17)
      secretion was stronger in asymptomatic subjects, in response to F1, as well as in
      cured cutaneous leishmaniasis after NH36 stimulation. While no IL-10 secretion
      was determined by F1, a granzyme B increase was detected in supernatants from
      cured patients after stimulation with either NH36 or F1. These data demonstrate
      that F1 is the domain of NH36 that induces a recall cellular response in
      individuals with acquired resistance to the infection by L. (L.) infantum. In
      addition, F1 and NH36 discriminated the IgG3 humoral response in patients with
      active visceral leishmaniasis due to L. (L.) donovani (Ethiopia) and L. (L.)
      infantum (Spain) from that of endemic and non-endemic area controls. NH36 showed
      higher reactivity with sera from L. (L.) donovani-infected individuals,
      indicating species specificity. We conclude that the F1 domain, previously
      characterized as an inducer of the Th1 and Th17 responses in cured/exposed
      patients infected with L. (L.) infantum chagasi, may also be involved in the
      generation of a protective response against L. (L.) infantum and represents a
      potential vaccine candidate for the control of human leishmaniasis alone, or in
      combination with other HLA epitopes/antigens.

PMID- 28747912
TI  - Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA
      Binding Protein 2-Deficient Patients.
AB  - GATA binding protein 2 (GATA2) deficiency is a rare disorder of hematopoiesis,
      lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in
      the GATA2 gene. Clinical manifestations range from neutropenia, lymphedema,
      deafness, to severe viral and mycobacterial infections, bone marrow failure, and
      acute myeloid leukemia. Patients also present with monocytopenia, dendritic cell,
      B- and natural killer (NK)-cell deficiency. We studied the T-cell and NK-cell
      compartments of four GATA2-deficient patients to assess if changes in these
      lymphocyte populations could be correlated with clinical phenotype. Patients with
      more severe clinical complications demonstrated a senescent T-cell phenotype
      whereas patients with lower clinical score had undetectable changes relative to
      controls. In contrast, patients' NK-cells demonstrated an immature/activated
      phenotype that did not correlate with clinical score, suggesting an intrinsic NK
      cell defect. These studies will help us to determine the contribution of T- and
      NK-cell dysregulation to the clinical phenotype of GATA2 patients, and may help
      to establish the most accurate therapeutic options for these patients.
      Asymptomatic patients may be taken into consideration for hematopoietic stem cell
      transplantation when dysregulation of T-cell and NK-cell compartment is present.

PMID- 28747851
TI  - Search for direct pair production of supersymmetric top quarks decaying to all
      hadronic final states in pp collisions at [Formula: see text].
AB  - Results are reported from a search for the pair production of top squarks, the
      supersymmetric partners of top quarks, in final states with jets and missing
      transverse momentum. The data sample used in this search was collected by the CMS
      detector and corresponds to an integrated luminosity of 18.9[Formula: see text]
      of proton-proton collisions at a centre-of-mass energy of 8[Formula: see text]
      produced by the LHC. The search features novel background suppression and
      prediction methods, including a dedicated top quark pair reconstruction
      algorithm. The data are found to be in agreement with the predicted backgrounds.
      Exclusion limits are set in simplified supersymmetry models with the top squark
      decaying to jets and an undetected neutralino, either through a top quark or
      through a bottom quark and chargino. Models with the top squark decaying via a
      top quark are excluded for top squark masses up to 755[Formula: see text] in the
      case of neutralino masses below 200[Formula: see text]. For decays via a
      chargino, top squark masses up to 620[Formula: see text] are excluded, depending
      on the masses of the chargino and neutralino.

PMID- 28747914
TI  - Extrinsic Protein Tyrosine Phosphatase Non-Receptor 22 Signals Contribute to CD8
      T Cell Exhaustion and Promote Persistence of Chronic Lymphocytic Choriomeningitis
      Virus Infection.
AB  - A genetic variant of the protein tyrosine phosphatase non-receptor 22 (PTPN22) is
      associated with a wide range of autoimmune diseases; however, the reasons behind
      its prevalence in the general population remain not completely understood. Recent
      evidence highlights an important role of autoimmune susceptibility genetic
      variants in conferring resistance against certain pathogens. In this study, we
      examined the role of PTPN22 in persistent infection in mice lacking PTPN22
      infected with lymphocytic choriomeningitis virus clone 13. We found that lack of
      PTPN22 in mice resulted in viral clearance 30 days after infection, which was
      reflected in their reduced weight loss and overall improved health. PTPN22-/-
      mice exhibited enhanced virus-specific CD8 and CD4 T cell numbers and
      functionality and reduced exhausted phenotype. Moreover, mixed bone marrow
      chimera studies demonstrated no differences in virus-specific CD8 T cell
      accumulation and function between the PTPN22+/+ and PTPN22-/- compartments,
      showing that the effects of PTPN22 on CD8 T cells are T cell-extrinsic. Together,
      these findings identify a CD8 T cell-extrinsic role for PTPN22 in weakening early
      CD8 T cell responses to collectively promote persistence of a chronic viral
      infection.

PMID- 28747913
TI  - Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But
      Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency.
AB  - BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless treated with
      hematopoietic stem cell transplant. Delay in diagnosis is common without newborn
      screening. Family history of infant death due to infection or known SCID (FH) has
      been associated with earlier diagnosis. OBJECTIVE: The aim of this study was to
      identify the clinical features that affect age at diagnosis (AD) and time to the
      diagnosis of SCID. METHODS: From 2005 to 2016, 147 SCID patients were referred to
      the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age
      at presentation (AP), and AD were selected for study. RESULTS: A total of 88
      different SCID gene mutations were identified in 94 patients, including 49 IL2RG
      mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C
      mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of
      29 mutations were previously unreported. Eighty-three of the 94 patients
      fulfilled the selection criteria. Their median AD was 4 months, and the time to
      diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29
      patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette-Guerin
      (BCG) vaccine infection (n = 19) were the commonest infections. The median age
      for candidiasis and BCG infection documented were 3 months and 4 months,
      respectively. The median absolute lymphocyte count (ALC) was 1.05 * 109/L with
      over 88% patients below 3 * 109/L. Positive FH was associated with earlier AP by
      1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time
      to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p
      = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections
      were not associated with age or time to diagnosis. CONCLUSION: FH was useful to
      aid earlier diagnosis but was overlooked by clinicians and not by parents.
      Similarly, typical clinical features of SCID were not recognized by clinicians to
      shorten the time to diagnosis. We suggest that lymphocyte subset should be
      performed for any infant with one or more of the following four clinical
      features: FH, candidiasis, BCG infections, and ALC below 3 * 109/L.

PMID- 28747915
TI  - T Cell Lymphoma and Leukemia in Severe Combined Immunodeficiency Pigs following
      Bone Marrow Transplantation: A Case Report.
AB  - After the discovery of naturally occurring severe combined immunodeficiency
      (SCID) within a selection line of pigs at Iowa State University, we found two
      causative mutations in the Artemis gene: haplotype 12 (ART12) and haplotype 16
      (ART16). Bone marrow transplants (BMTs) were performed to create genetically SCID
      and phenotypically immunocompetent breeding animals to establish a SCID colony
      for further characterization and research utilization. Of nine original BMT
      transfer recipients, only four achieved successful engraftment. At approximately
      11 months of age, both animals homozygous for the ART16 mutation were diagnosed
      with T cell lymphoma. One of these ART16/ART16 recipients was a male who received
      a transplant from a female sibling; the tumors in this recipient consist
      primarily of Y chromosome-positive cells. The other ART16/ART16 animal also
      presented with leukemia in addition to T cell lymphoma, while one of the
      ART12/ART16 compound heterozygote recipients presented with a nephroblastoma at a
      similar age. Human Artemis SCID patients have reported cases of lymphoma
      associated with a "leaky" Artemis phenotype. The naturally occurring Artemis SCID
      pig offers a large animal model more similar to human SCID patients and may offer
      a naturally occurring cancer model and provides a valuable platform for therapy
      development.

PMID- 28747916
TI  - Interferon-Gamma DNA Methylation Is Affected by Mycophenolic Acid but Not by
      Tacrolimus after T-Cell Activation.
AB  - Immunosuppressive drug therapy is required to treat patients with autoimmune
      disease and patients who have undergone organ transplantation. The main targets
      of the immunosuppressive drugs tacrolimus and mycophenolic acid (MPA; the active
      metabolite of mycophenolate mofetil) are T cells. It is currently unknown whether
      these immunosuppressive drugs have an effect on DNA methylation-an epigenetic
      regulator of cellular function. Here, we determined the effect of tacrolimus and
      MPA on DNA methylation of the gene promoter region of interferon gamma
      (IFNgamma), a pro-inflammatory cytokine. Total T cells, naive T cells
      (CCR7+CD45RO-), and memory T cells (CD45RO+ and CCR7-CD45RO-) were isolated from
      CMV seropositive healthy controls and stimulated with alpha-CD3/CD28 in the
      presence or absence of tacrolimus or MPA. DNA methylation of the IFNgamma
      promoter region was quantified by pyrosequencing at 4 h, days 1, 3, and 4 after
      stimulation. In parallel, T-cell differentiation, and IFNgamma protein production
      were analyzed by flow cytometry at days 1 and 3 after stimulation. Our results
      show that MPA induced changes in IFNgamma DNA methylation of naive T cells; MPA
      counteracted the decrease in methylation after stimulation. Tacrolimus did not
      affect IFNgamma DNA methylation of naive T cells. In the memory T cells, both
      immunosuppressive drugs did not affect IFNgamma DNA methylation. Differentiation
      of naive T cells into a central-memory-like phenotype (CD45RO+) was inhibited by
      both immunosuppressive drugs, while differentiation of memory T cells remained
      unaffected by both MPA and tacrolimus. IFNgamma protein production was suppressed
      by tacrolimus. Our results demonstrate that MPA influenced IFNgamma DNA
      methylation of naive T cells after stimulation of T cells, while tacrolimus had
      no effect. Both tacrolimus and MPA did not affect IFNgamma DNA methylation of
      memory T cells.

PMID- 28747917
TI  - Upregulation of Intestinal Barrier Function in Mice with DSS-Induced Colitis by a
      Defined Bacterial Consortium Is Associated with Expansion of IL-17A Producing
      Gamma Delta T Cells.
AB  - Bacterial consortium transplantation (BCT) is a promising alternative to fecal
      microbiota transplantation in treating inflammatory bowel disease (IBD). Here, we
      showed that a defined bacterial consortium derived from healthy mice was able to
      enhance the intestinal barrier function of mice with dextran sulfate sodium (DSS)
      induced colitis. Interestingly, we found that the bacterial consortium
      significantly promoted the expansion of IL-17A-producing gammadeltaT
      (gammadeltaT17) cells in colonic lamina propria, which was closely associated
      with changing of intestinal microbial composition. The increased IL-17A secretion
      upon treatment with microbial products derived from the bacterial consortium was
      accompanied with upregulation of TLR2 expression by gammadeltaT cells, and it
      might be responsible for the upregulation of mucosal barrier function through IL
      17R-ACT1-mediated recovery of the disrupted occludin subcellular location.
      Changing of some specific microbial groups such as Bifidobacterium and Bacillus
      spp. was closely correlated with the promotion of TLR2+ gammadeltaT cells. Our
      results support that BCT can restore the alliance between commensal microbiota
      and intestinal gammadeltaT cells, which contributes to the improvement of
      intestinal barrier function. This study provides new insight into the development
      of bacteria transplantation therapy for the treatment of IBD.

PMID- 28747919
TI  - Intraspecific Trait Variation and Coordination: Root and Leaf Economics Spectra
      in Coffee across Environmental Gradients.
AB  - Hypotheses on the existence of a universal "Root Economics Spectrum" (RES) have
      received arguably the least attention of all trait spectra, despite the key role
      root trait variation plays in resource acquisition potential. There is growing
      interest in quantifying intraspecific trait variation (ITV) in plants, but there
      are few studies evaluating (i) the existence of an intraspecific RES within a
      plant species, or (ii) how a RES may be coordinated with other trait spectra
      within species, such as a leaf economics spectrum (LES). Using Coffea arabica
      (Rubiaceae) as a model species, we measured seven morphological and chemical
      traits of intact lateral roots, which were paired with information on four key
      LES traits. Field collections were completed across four nested levels of
      biological organization. The intraspecific trait coefficient of variation (cv)
      ranged from 25 to 87% with root diameter and specific root tip density showing
      the lowest and highest cv, respectively. Between 27 and 68% of root ITV was
      explained by site identity alone for five of the seven traits measured. A single
      principal component explained 56.2% of root trait covariation, with plants
      falling along a RES from resource acquiring to conserving traits. Multiple factor
      analysis revealed significant orthogonal relationships between root and leaf
      spectra. RES traits were strongly orthogonal with respect to LES traits,
      suggesting these traits vary independently from one another in response to
      environmental cues. This study provides among the first evidence that plants from
      the same species differentiate from one another along an intraspecific RES. We
      find that in one of the world's most widely cultivated crops, an intraspecific
      RES is orthogonal to an intraspecific LES, indicating that above and belowground
      responses of plants to managed (or natural) environmental gradients are likely to
      occur independently from one another.

PMID- 28747918
TI  - Root-Knot and Cyst Nematodes Activate Procambium-Associated Genes in Arabidopsis
      Roots.
AB  - Developmental plasticity is one of the most striking features of plant
      morphogenesis, as plants are able to vary their shapes in response to
      environmental cues. Biotic or abiotic stimuli often promote organogenesis events
      in plants not observed under normal growth conditions. Root-knot nematodes (RKNs)
      are known to parasitize multiple species of rooting plants and to induce
      characteristic tissue expansion called galls or root-knots on the roots of their
      hosts by perturbing the plant cellular machinery. Galls contain giant cells (GCs)
      and neighboring cells, and the GCs are a source of nutrients for the parasitizing
      nematode. Highly active cell proliferation was observed in galls. However, the
      underlying mechanisms that regulate the symptoms triggered by the plant-nematode
      interaction have not yet been elucidated. In this study, we deciphered the
      molecular mechanism of gall formation with an in vitro infection assay system
      using RKN Meloidogyne incognita, and the model plant Arabidopsis thaliana. By
      taking advantages of this system, we performed next-generation sequencing-based
      transcriptome profiling, and found that the expression of procambium identity
      associated genes were enriched during gall formation. Clustering analyses with
      artificial xylogenic systems, together with the results of expression analyses of
      the candidate genes, showed a significant correlation between the induction of
      gall cells and procambium-associated cells. Furthermore, the promoters of several
      procambial marker genes such as ATHB8, TDR and WOX4 were activated not only in M.
      incognita-induced galls, but similarly in M. javanica induced-galls and
      Heterodera schachtii-induced syncytia. Our findings suggest that phytoparasitic
      nematodes modulate the host's developmental regulation of the vascular stem cells
      during gall formation.

PMID- 28747847
TI  - Measurements of top-quark pair differential cross-sections in the lepton+jets
      channel in pp collisions at [Formula: see text] using the ATLAS detector.
AB  - Measurements of normalized differential cross-sections of top-quark pair
      production are presented as a function of the top-quark, [Formula: see text]
      system and event-level kinematic observables in proton-proton collisions at a
      centre-of-mass energy of [Formula: see text]. The observables have been chosen to
      emphasize the [Formula: see text] production process and to be sensitive to
      effects of initial- and final-state radiation, to the different parton
      distribution functions, and to non-resonant processes and higher-order
      corrections. The dataset corresponds to an integrated luminosity of 20.3
      fb[Formula: see text], recorded in 2012 with the ATLAS detector at the CERN Large
      Hadron Collider. Events are selected in the lepton+jets channel, requiring
      exactly one charged lepton and at least four jets with at least two of the jets
      tagged as originating from a b-quark. The measured spectra are corrected for
      detector effects and are compared to several Monte Carlo simulations. The results
      are in fair agreement with the predictions over a wide kinematic range.
      Nevertheless, most generators predict a harder top-quark transverse momentum
      distribution at high values than what is observed in the data. Predictions beyond
      NLO accuracy improve the agreement with data at high top-quark transverse
      momenta. Using the current settings and parton distribution functions, the
      rapidity distributions are not well modelled by any generator under
      consideration. However, the level of agreement is improved when more recent sets
      of parton distribution functions are used.

PMID- 28747920
TI  - Unraveling Key Metabolomic Alterations in Wheat Embryos Derived from Freshly
      Harvested and Water-Imbibed Seeds of Two Wheat Cultivars with Contrasting
      Dormancy Status.
AB  - Untimely rains in wheat fields during harvest season can cause pre-harvest
      sprouting (PHS), which deteriorates the yield and quality of wheat crop.
      Metabolic homeostasis of the embryo plays a role in seed dormancy, determining
      the status of the maturing grains either as dormant (PHS-tolerant) or non-dormant
      (PHS-susceptible). Very little is known for direct measurements of global
      metabolites in embryonic tissues of dormant and non-dormant wheat seeds. In this
      study, physiologically matured and freshly harvested wheat seeds of PHS-tolerant
      (cv. Sukang, dormant) and PHS-susceptible (cv. Baegjoong, non-dormant) cultivars
      were water-imbibed, and the isolated embryos were subjected to high-throughput,
      global non-targeted metabolomic profiling. A careful comparison of identified
      metabolites between Sukang and Baegjoong embryos at 0 and 48 h after imbibition
      revealed that several key metabolic pathways [such as: lipids, fatty acids,
      oxalate, hormones, the raffinose family of oligosaccharides (RFOs), and amino
      acids] and phytochemicals were differentially regulated between dormant and non
      dormant varieties. Most of the membrane lipids were highly reduced in Baegjoong
      compared to Sukang, which indicates that the cell membrane instability in
      response to imbibition could also be a key factor in non-dormant wheat varieties
      for their untimely germination. This study revealed that several key marker
      metabolites (e.g., RFOs: glucose, fructose, maltose, and verbascose), were highly
      expressed in Baegjoong after imbibition. Furthermore, the data showed that the
      key secondary metabolites and phytochemicals (vitexin, chrysoeriol, ferulate,
      salidroside and gentisic acid), with known antioxidant properties, were
      comparatively low at basal levels in PHS-susceptible, non-dormant cultivar,
      Baegjoong. In conclusion, the results of this investigation revealed that after
      imbibition the metabolic homeostasis of dormant wheat is significantly less
      affected compared to non-dormant wheat. The inferences from this study combined
      with proteomic and transcriptomic studies will advance the molecular
      understanding of the pathways and enzyme regulations during PHS.

PMID- 28747921
TI  - Unreduced Megagametophyte Production in Lemon Occurs via Three Meiotic
      Mechanisms, Predominantly Second-Division Restitution.
AB  - Unreduced (2n) gametes have played a pivotal role in polyploid plant evolution
      and are useful for sexual polyploid breeding in various species, particularly for
      developing new seedless citrus varieties. The underlying mechanisms of 2n gamete
      formation were recently revealed for Citrus reticulata but remain poorly
      understood for other citrus species, including lemon (C. limon [L.] Burm. f.).
      Here, we investigated the frequency and causal meiotic mechanisms of 2n
      megagametophyte production in lemon. We genotyped 48progeny plants of two lemon
      genotypes, "Eureka Frost" and "Fino", using 16 Simple Sequence Repeat (SSR) and
      18 Single Nucleotide Polymorphism (SNP) markers to determine the genetic origin
      of the progenies and the underlying mechanisms for 2n gamete formation. We
      utilized a maximum-likelihood method based on parental heterozygosity restitution
      (PHR) of centromeric markers and analysis of PHR patterns along the chromosome.
      The frequency of 2n gamete production was 4.9% for "Eureka Frost" and 8.3% for
      "Fino", with three meiotic mechanisms leading to 2n gamete formation. We
      performed the maximum-likelihood method at the individual level via centromeric
      marker analysis, finding that 88% of the hybrids arose from second-division
      restitution (SDR), 7% from first-division restitution (FDR) or pre-meiotic
      doubling (PRD), and 5% from post-meiotic genome doubling (PMD). The pattern of
      PHR along LG1 confirmed that SDR is the main mechanism for 2n gamete production.
      Recombination analysis between markers in this LG revealed partial chiasma
      interference on both arms. We discuss the implications of these restitution
      mechanisms for citrus breeding and lemon genetics.

PMID- 28747922
TI  - Identification of Major Quantitative Trait Loci for Seed Oil Content in Soybeans
      by Combining Linkage and Genome-Wide Association Mapping.
AB  - Soybean oil is the most widely produced vegetable oil in the world and its
      content in soybean seed is an important quality trait in breeding programs. More
      than 100 quantitative trait loci (QTLs) for soybean oil content have been
      identified. However, most of them are genotype specific and/or environment
      sensitive. Here, we used both a linkage and association mapping methodology to
      dissect the genetic basis of seed oil content of Chinese soybean cultivars in
      various environments in the Jiang-Huai River Valley. One recombinant inbred line
      (RIL) population (NJMN-RIL), with 104 lines developed from a cross between M8108
      and NN1138-2, was planted in five environments to investigate phenotypic data,
      and a new genetic map with 2,062 specific-locus amplified fragment markers was
      constructed to map oil content QTLs. A derived F2 population between MN-5 (a line
      of NJMN-RIL) and NN1138-2 was also developed to confirm one major QTL. A soybean
      breeding germplasm population (279 lines) was established to perform a genome
      wide association study (GWAS) using 59,845 high-quality single nucleotide
      polymorphism markers. In the NJMN-RIL population, 8 QTLs were found that
      explained a range of phenotypic variance from 6.3 to 26.3% in certain planting
      environments. Among them, qOil-5-1, qOil-10-1, and qOil-14-1 were detected in
      different environments, and qOil-5-1 was further confirmed using the secondary F2
      population. Three loci located on chromosomes 5 and 20 were detected in a 2-year
      long GWAS, and one locus that overlapped with qOil-5-1 was found repeatedly and
      treated as the same locus. qOil-5-1 was further localized to a linkage
      disequilibrium block region of approximately 440 kb. These results will not only
      increase our understanding of the genetic control of seed oil content in soybean,
      but will also be helpful in marker-assisted selection for breeding high seed oil
      content soybean and gene cloning to elucidate the mechanisms of seed oil content.

PMID- 28747925
TI  - Manipulating Planting Density and Nitrogen Fertilizer Application to Improve
      Yield and Reduce Environmental Impact in Chinese Maize Production.
AB  - Relatively low nitrogen (N) efficiency and heavy environmental costs caused by
      excessive N fertilizer applications with outdated fertilization techniques are
      current cultivation production problems with maize among smallholders in North
      China Plain. Although many studies have examined agronomical strategies for
      improving yields and N use, the integrated effects of these measures and the
      associated environmental costs are not well understood. We conducted a 2-year
      field study with two densities (67,500 plants ha-1, which was similar to local
      farmers' practices, and 90,000 plants ha-1) and three N rates (0, 180, and 360 kg
      ha-1, the rate local farmers' commonly apply) to test the integrated effects for
      maize production at Wuqiao experimental station in North China Plain. The higher
      planting density produced significant increases in grain yield (GY), N use
      efficiency (NUE), agronomic N efficiency (AEN), and N partial productivity (PFPN)
      by 6.6, 3.9, 24.7, and 8.8%, respectively; in addition, N2O emission and
      greenhouse gas intensity decreased by 7.3 and 4.3%, respectively. With a lower N
      application rate, from 360 to 180 kg ha-1, GY was unchanged, and NUE, AEN, and
      PFPN all significantly increased by 6.2, 96.0, and 98.7%, respectively; in
      addition, N2O emission and greenhouse gas intensity decreased by 61.5 and 46.2%,
      respectively. The optimized N rate (180 kg N ha-1) for the 90,000 plants ha-1
      treatment achieved the highest yield with only 50% of the N fertilizer input
      commonly employed by local farmers' (360 kg N ha-1), which contributed to the
      increased N-uptake and N-transfer capacity. Therefore, our study demonstrated
      that agronomical methods such as increasing planting density with reasonable N
      application could be useful to obtain higher GY along with efficient N management
      to help lower environmental costs of maize production.

PMID- 28747927
TI  - Clinical Pearls.

PMID- 28747924
TI  - Endocytosis of AtRGS1 Is Regulated by the Autophagy Pathway after D-Glucose
      Stimulation.
AB  - Sugar, as a signal molecule, has significant functions in signal transduction in
      which the seven-transmembrane regulator of G-protein signaling (RGS1) protein
      participates. D-Glucose causes endocytosis of the AtRGS1, leading to the physical
      uncoupling of AtRGS1 from AtGPA1 and thus a release of the GAP activity and
      concomitant sustained activation of G-protein signaling. Autophagy involves in
      massive degradation and recycling of cytoplasmic components to survive
      environmental stresses. The function of autophagy in AtRGS1 endocytosis during D
      glucose stimulation has not been elucidated. In this study, we investigate the
      relationship between autophagy and AtRGS1 in response to D-glucose. Our findings
      demonstrated that AtRGS1 mediated the activation of autophagy by affecting the
      activities of the five functional groups of protein complexes and promoted the
      formation of autophagosomes under D-glucose application. When the autophagy
      pathway was interrupted, AtRGS1 recovery increased and endocytosis of ATRGS1 was
      inhibited, indicating that autophagy pathway plays an important role in
      regulating the endocytosis and recovery of AtRGS1 after D-glucose stimulation.

PMID- 28747928
TI  - It's More Complicated than Myth Busting: Parents Deciding About Stimulant Use for
      their Children.

PMID- 28747923
TI  - Mapping QTL for Seed Germinability under Low Temperature Using a New High-Density
      Genetic Map of Rice.
AB  - Mapping major quantitative trait loci (QTL) responsible for rice seed
      germinability under low temperature (GULT) can provide valuable genetic source
      for improving cold tolerance in rice breeding. In this study, 124 rice backcross
      recombinant inbred lines (BRILs) derived from a cross indica cv. Changhui 891 and
      japonica cv. 02428 were genotyped through re-sequencing technology. A bin map was
      generated which includes 3057 bins covering distance of 1266.5 cM with an average
      of 0.41 cM between markers. On the basis of newly constructed high-density
      genetic map, six QTL were detected ranging from 40 to 140 kb on Nipponbare
      genome. Among these, two QTL qCGR8 and qGRR11 alleles shared by 02428 could
      increase GULT and seed germination recovery rate after cold stress, respectively.
      However, qNGR1 and qNGR4 may be two major QTL affecting indica Changhui
      891germination under normal condition. QTL qGRR1 and qGRR8 affected the seed
      germination recovery rate after cold stress and the alleles with increasing
      effects were shared by the Changhui 891 could improve seed germination rate after
      cold stress dramatically. These QTL could be a highly valuable genetic factors
      for cold tolerance improvement in rice lines. Moreover, the BRILs developed in
      this study will serve as an appropriate choice for mapping and studying genetic
      basis of rice complex traits.

PMID- 28747926
TI  - Agonist-induced activation of human FFA1 receptor signals to extracellular signal
      regulated kinase 1 and 2 through Gq- and Gi-coupled signaling cascades.
AB  - BACKGROUND: FFA1 is abundantly expressed in the liver, skeletal muscle, monocytes
      and nervous system, but is particularly abundant in pancreatic beta cells. It is
      widely believed that FFA1 exerts its regulatory roles in a variety of
      physiological and pathological functions. In response to oleic acid, FFA1 has
      been shown to induce the activation of extracellular signal-regulated kinase 1
      and 2 (ERK1/2) through a mechanism involving EGFR transactivation in a breast
      cancer cell line. However, the underlying molecular mechanism for ERK1/2
      activation mediated by n-6 free fatty acid (LA) in HEK293 cells remains to be
      further elucidated. METHODS: A FLAG-FFA1 vector was stably expressed in HEK293
      cells. Western blot analysis was applied to investigate the change in LA-induced
      ERK1/2 phosphorylation change in response to kinase inhibitors. Arrestin-2/3
      specific siRNA was used to analyze the effect of arrestin-2/3 knockdown on FFA1
      mediated ERK1/2 activation. RESULTS: We proved that activation of ERK1/2 by LA
      was rapid, peaking at 5 min. Further experiments proved that FFA1 couples to a Gq
      protein and activates PI-PLC, which induces the IP3/Ca2+ and DAG/PKC signal
      pathways, both of which are involved in ERK1/2 activation. We also showed that
      there is no EGFR transactivation, arrestin-2/3 or Gbetagamma pathway
      participation in ERK1/2 phosphorylation. Treating cells with PTX abolished ERK1/2
      activation at a late time point (>=20 min), indicating a critical role for Gi
      subunits in FFA1-mediated ERK1/2 activation. CONCLUSIONS: Our study provides a
      detailed delineation of the LA-mediated activation of ERK1/2 in HEK293 cells that
      are stably transfected with human FFA1. We also present evidence of Gi/Gq-induced
      synergism in the regulation of ERK1/2 phosphorylation. These observations may
      provide new insights into the pharmacological effects of FFA1 and the
      physiological functions modulated by FFA1-mediated activation of ERK1/2.

PMID- 28747929
TI  - Relationship between Bullying and Suicidal Behaviour in Youth presenting to the
      Emergency Department.
AB  - OBJECTIVE: Increasing numbers of adolescents are visiting emergency departments
      with suicidal ideation. This study examines the relationship between bullying and
      suicidal ideation in emergency department settings. METHOD: A chart review was
      conducted for all patients under 18 years of age presenting with a mental health
      complaint to the emergency departments at Kingston General or Hotel Dieu
      Hospitals in Kingston, Canada, between January 2011 and January 2015. Factors
      such as age, gender, history of abuse, history of bullying, type and time of
      bullying, and diagnoses were documented. RESULTS: 77% of the adolescents had
      experienced bullying, while 68.9% had suicide ideation at presentation. While
      controlling for age, gender, grade, psychiatric diagnosis, and abuse, a history
      of bullying was the most significant predictor of suicidal ideation. Individuals
      in this study who reported cyber bullying were 11.5 times more likely to have
      suicidal ideation documented on presentation, while individuals reporting verbal
      bullying were 8.4 times more likely. CONCLUSIONS: The prevalence of bullying in
      adolescent patients presenting to emergency departments is high. The relationship
      found between suicidal ideation and bullying demonstrates that clinicians should
      ask questions about bullying as a risk factor for suicide ideation during the
      assessment of children and adolescents.

PMID- 28747930
TI  - Parental Involvement and Child and Adolescent Eating Disorders: Perspectives from
      Residents in Psychiatry, Pediatrics, and Family Medicine.
AB  - OBJECTIVES: Best practice guidelines encourage the involvement of parents in the
      assessment and treatment of child/adolescent eating disorders (ED). This study
      investigated medical residents' perspectives regarding parental involvement as
      well as their expectations for future practice in the assessment and treatment of
      ED. METHOD: Five hundred and eighty-four medical residents from 17 Canadian
      residency programs specializing in family medicine, pediatrics, and psychiatry
      completed a web-based survey. Questions pertained to assessment and treatment
      practices for child/adolescent ED. Analyses included ANOVAs, paired t-tests, and,
      for residents who endorsed family involvement (N = 444), qualitative content
      analysis. RESULTS: Overall, residents reported that they "mostly" agreed with the
      involvement of family in the assessment and treatment of ED. Residents'
      endorsement of family involvement in both domains increased according to the
      extent of ED training received. Four major themes emerged from the content
      analysis of family involvement and included recommendations in line with evidence
      based models and unspecified, passive involvement in the assessment and recovery
      process. CONCLUSIONS: Many residents endorse family involvement in both
      assessment and treatment; however, understanding of the nature of such
      involvement is often vague. Training in evidence-based protocols is necessary for
      residents planning to engage in multi-disciplinary assessment, referral, and/or
      treatment in their future practice.

PMID- 28747931
TI  - Is the National Guideline Clearinghouse a Trustworthy Source of Practice
      Guidelines for Child and Youth Anxiety and Depression?
AB  - OBJECTIVE: Innovative strategies that facilitate the use of high quality practice
      guidelines (PG) are needed. Accordingly, repositories designed to simplify access
      to PGs have been proposed as a critical component of the network of linked
      interventions needed to drive increased PG implementation. The National Guideline
      Clearinghouse (NGC) is a free, international online repository. We investigated
      whether it is a trustworthy source of child and youth anxiety and depression PGs.
      METHOD: English language PGs published between January 2009 and February 2016
      relevant to anxiety or depression in children and adolescents (<= 18 years of
      age) were eligible. Two trained raters assessed PG quality using Appraisal of
      Guidelines for Research and Evaluation (AGREE II). Scores on at least three AGREE
      II domains (stakeholder involvement, rigor of development, and editorial
      independence) were used to designate PGs as: i) minimum quality (>= 50%); and ii)
      high quality (>= 70%). RESULTS: Eight eligible PGs were identified (depression,
      n=6; anxiety and depression, n=1; social anxiety disorder, n=1). Four of eight
      PGs met minimum quality criteria; three of four met high quality criteria.
      CONCLUSIONS: At present, NGC users without the time and special skills required
      to evaluate PG quality may unknowingly choose flawed PGs to guide decisions about
      child and youth anxiety and depression. The recent NGC decision to explore the
      inclusion of PG quality profiles based on Institute of Medicine standards
      provides needed leadership that can strengthen PG repositories, prevent harm and
      wasted resources, and build PG developer capacity.

PMID- 28747932
TI  - Prescribing Practices of Quetiapine for Insomnia at a Tertiary Care Inpatient
      Child and Adolescent Psychiatry Unit: A Continuous Quality Improvement Project.
AB  - OBJECTIVE: To examine the prescribing practices of quetiapine for insomnia at a
      tertiary care child and adolescent psychiatric inpatient unit. METHOD: A
      retrospective chart review was conducted on all admissions in 2013 involving
      night-time only prescription of quetiapine. We examined patient demographics,
      discharge diagnoses, physician's written indications for prescriptions, and
      maximum doses used. If used for insomnia only, we noted any documentation of past
      sedative trials, concurrent prescriptions of other sedative agents, whether
      quetiapine was started in hospital or continued as a part of a community regimen,
      and whether quetiapine was continued on discharge. RESULTS: Of 720 admissions, 83
      (11.5%) involved the prescription of night-time only quetiapine, and 47 of the 83
      (57%) were for insomnia only. Of patients prescribed quetiapine for insomnia
      only, most common discharge diagnoses were anxiety disorder (35%), depressive
      disorder (27%), eating disorder (27%), and Cluster B/borderline personality
      traits/disorder (25%). Mean age was 15.4 years; mean maximum dose was 41.2 mg.
      Quetiapine was often started during admission (89.5%) and continued on discharge
      (66%). About 40% of these cases involved concurrent prescription of other
      sedative agents. Most patients (81%) had no documented history of prior sedative
      trials. CONCLUSIONS: Quetiapine is used not infrequently for the management of
      insomnia in adolescents in tertiary mental health settings. We highlight the
      nuances associated with the prescription of quetiapine for the treatment of
      insomnia in the unique setting of the child and adolescent psychiatric inpatient
      unit, emphasizing the importance of weighing short-term use with potential long
      term adverse consequences if continued in the community setting.

PMID- 28747933
TI  - I think I'm Going to be Sick: An Eight-Year-Old Boy with Emetophobia and
      Secondary Food Restriction.
AB  - We present a case of an eight-year-old boy with a specific phobia of vomiting who
      developed subsequent food restriction and weight loss. Our case report includes a
      review of treatment modalities for specific phobias including cognitive
      behavioural and exposure therapy in young children and the importance of parental
      involvement in the treatment process. After an initial assessment and diagnosis
      of this boy with emetophobia, treatment took place over ten subsequent visits,
      one hour each in duration. His treatment included a cognitive approach utilizing
      exposure therapy to re-introduce foods to his diet, working through a fear
      hierarchy, addressing cognitive distortions/misconceptions and psychoeducational
      supports. Intermittent reinforcement was applied to help extinguish what we
      believe was an associatively learned fear of vomiting. Outcomes of the treatment
      were measured by changes in behaviour and overall increase in food intake
      reported by the patient's parents. On completion of treatment, the family was no
      longer concerned with the amount and variety of food he was eating, the patient
      reported less nausea, and he was more likely to eat in public. A post-treatment
      three-week telephone follow-up showed continued gains. Congruent with reported
      literature , this case confirms and highlights the efficacy of exposure therapy
      and age-appropriate cognitive treatment adaptations in treatment of emetophobia.
      In addition, parental education and participation is recommended in treatment of
      child cases.

PMID- 28747934
TI  - Avoidant/Restrictive Food Intake Disorder in an 11-Year Old South American Boy:
      Medical and Cultural Challenges.
AB  - Avoidant/Restrictive Food Intake Disorder (ARFID) is new in the DSM-5, replacing
      the DSM-IV-TR diagnosis of Feeding Disorder of Infancy or Early Childhood. ARFID
      has no age criterion, and therefore addresses eating disturbances across the
      lifespan. This report illustrates the case of an 11-year-old boy of Colombian
      ancestry with ARFID and explores the role of culture in the diagnosis of ARFID.
      To date, literature describing this disorder is limited. ARFID is often seen in
      the child and adolescent population and can have significant medical
      consequences, including weight loss, hemodynamic instability, and growth
      retardation. Studies examining the potential cultural challenges of diagnosing
      and treating ARFID would benefit patients, as well as health professionals
      working in primary care, pediatrics, and psychiatry. This paper is intended to
      inform the reader about this multifaceted disorder, and to generate interest for
      future research.

PMID- 28747935
TI  - Exploratory Study of the Clinical Characteristics of Adolescent Girls with a
      History of Physical or Sexual Abuse Consulting in a Mood Disorder Clinic.
AB  - OBJECTIVE: To examine the clinical characteristics of adolescent girls consulting
      in a mood disorder clinic with a history of physical or sexual abuse. METHOD: A
      retrospective review was conducted of the charts of 55 adolescent girls
      consulting in a mood disorder clinic. An analysis grid was used to gather data on
      demographics, personal antecedents, symptoms and diagnoses. Girls with a history
      of physical or sexual abuse were compared with girls without such a history.
      Univariate analyses and a logistic regression analysis were performed. RESULTS:
      Adolescent girls with a history of physical or sexual abuse did not differ
      statistically from those without such a history in terms of depressive symptoms
      or type and number of diagnoses. However, proportionally more girls with a
      history of physical or sexual abuse presented self-harm and relational problems
      with their parents and peers. CONCLUSION: Both history of physical or sexual
      abuse and self-destructive behaviors are rooted in relational problems. The
      results show that these are related to one another among those adolescent girls.
      Clinically, these findings suggest that it is important for clinicians do a
      thorough exploration of self-destructive behaviors and family and peer relations
      when assessing depressed adolescent girls.

PMID- 28747936
TI  - Psychometric Properties of the Self-Perception Profile for Children in Children
      with Chronic Illness.
AB  - OBJECTIVE: The Self-Perception Profile for Children (SPPC) is a commonly used
      measure of self-concept in children, but little research has examined its
      psychometric properties in children newly-diagnosed with chronic illness. METHOD:
      Confirmatory factor analysis and examination of reliability and convergent and
      discriminant validity of the SPPC was conducted in 31 children newly-diagnosed
      with asthma, diabetes, epilepsy, food allergy, or juvenile arthritis. RESULTS:
      The unidimensionality of each domain of the SPPC was confirmed, internal
      reliability was robust (alpha=.83-.95), and inter-domain polychoric correlations
      ranged from weak to strong (rho=.05-.85) Convergent validity was demonstrated
      with measures of global self-concept and domains of quality of life. The Global
      Self-worth domain showed discriminant validity between children with and without
      comorbid mental disorder. CONCLUSIONS: Findings extend the psychometric
      properties of the SPPC as a valid and reliable scale in children newly-diagnosed
      with chronic illness.

PMID- 28747849
TI  - Search for squarks and gluinos in final states with jets and missing transverse
      momentum at [Formula: see text] =13 [Formula: see text]with the ATLAS detector.
AB  - A search for squarks and gluinos in final states containing hadronic jets,
      missing transverse momentum but no electrons or muons is presented. The data were
      recorded in 2015 by the ATLAS experiment in [Formula: see text] proton-proton
      collisions at the Large Hadron Collider. No excess above the Standard Model
      background expectation was observed in 3.2 [Formula: see text] of analyzed data.
      Results are interpreted within simplified models that assume R-parity is
      conserved and the neutralino is the lightest supersymmetric particle. An
      exclusion limit at the 95 % confidence level on the mass of the gluino is set at
      1.51 [Formula: see text] for a simplified model incorporating only a gluino octet
      and the lightest neutralino, assuming the lightest neutralino is massless. For a
      simplified model involving the strong production of mass-degenerate first- and
      second-generation squarks, squark masses below 1.03 [Formula: see text] are
      excluded for a massless lightest neutralino. These limits substantially extend
      the region of supersymmetric parameter space excluded by previous measurements
      with the ATLAS detector.

PMID- 28747938
TI  - Computed tomography angiography for imaging results of neochordal mitral valve
      repair.
AB  - INTRODUCTION: Degenerative mitral regurgitation is currently the most frequent
      indication for mitral valve repair. AIM: To visualize and assess the mid-term
      results of mitral valve repair with neochordae implantation, using computed
      tomography angiography (CTA) imaging. MATERIAL AND METHODS: The CTA with ECG
      gating and without modulation was applied in 10 patients to assess the results of
      a mitral valve sparing procedure. The results of 3 patients are presented. The
      patients were operated on for severe symptomatic degenerative mitral
      regurgitation, defined according to a modified Carpentier's functional
      classification. RESULTS: Neochordal repair, by placing expanded
      polytetrafluoroethylene sutures between the leading edge of the prolapsing
      segment and the corresponding papillary muscle, was conducted. From 1 to 3 double
      Gore-Tex loops were used. Leaflet clefts, if present, were sutured. All repairs
      included mitral valve ring annuloplasty. The CTA was performed at 20-24 months
      after the surgery. Long-axis views, reconstructed during mid-systole, seemed to
      be the most valuable. Good quality cardiac images, precisely presenting the
      mitral valve complex with its constituents, were obtained in the case of patients
      without obesity, with a relatively small anterior-posterior thorax dimension,
      with sinus, slow heart rhythm and quite good left ventricle contractility. The
      evaluation of the mitral valve included presence of calcifications, fibrosis or
      thickening, chordal insertion and coaptation points, and papillary muscle
      locations. Primary and secondary native chordae tendineae and artificial chordae
      were visualized. CONCLUSIONS: Contrast material-enhanced ECG-gated CTA applied
      after mitral valve repair with Gore-Tex neochordae allows one to obtain
      satisfactory mitral valve images, especially during mid-systole, and evaluate mid
      term results of the surgery in chosen patients.

PMID- 28747940
TI  - Surgical treatment for pulmonary aspergilloma - early and long-term results.
AB  - INTRODUCTION: Pulmonary aspergilloma is a difficult therapeutic problem due to
      the low effectiveness of conservative treatment and high surgical morbidity. AIM:
      To analyze the early and late results of surgical treatment for pulmonary
      aspergilloma. MATERIAL AND METHODS: From 2005 to 2015, 49 patients were treated
      surgically for pulmonary aspergilloma. Symptoms occurred in 85.7% of cases,
      including recurrent hemoptysis in 53%. A history of immunosuppressive therapy or
      chemotherapy was noted in 24.5% of patients. Complex aspergilloma was diagnosed
      in 79.6% of cases. Immunological test results were positive in 10.2%, and
      bronchoalveolar lavage samples were positive for Aspergillus species in 18.5% of
      cases. In 59.2% of patients, the surgical risk was assessed as ASA 3. Thirty
      seven patients underwent lobectomy, 3 - pneumonectomy, 7 - wedge resection, 1 -
      decortication, and 1 - cavernostomy. RESULTS: In-hospital mortality was 4.1%.
      Postoperative complications occurred in 63.3% of patients. The most common
      complications were: prolonged air leak (26.3%), arrhythmias (20.4%), residual
      pneumothorax (16.3%), respiratory failure (14.3%), atelectasis (12.3%), and
      bleeding (12.3%). Of the three patients that underwent pneumonectomy, one died,
      two required repeat thoracotomy because of bleeding, and all three required
      prolonged mechanical ventilation. Two patients died during the follow-up period.
      Aspergilloma did not recur in any of the patients who underwent pulmonary
      resection. CONCLUSIONS: Due to the high risk of complications, surgical treatment
      of pulmonary aspergilloma should be restricted to symptomatic patients in whom
      lobectomy can be performed. The long-term results of surgical treatment are good,
      preoperative symptoms abate in most patients, and the rate of aspergillosis
      recurrence is very low.

PMID- 28747942
TI  - Complex corrective procedure in surgical treatment of asymmetrical pectus
      excavatum.
AB  - AIM: In this study we analysed the early and late results of surgical treatment
      of asymmetrical pectus excavatum using complex surgery combining the Ravitch
      procedure and the Nuss procedure in the same general anaesthesia. MATERIAL AND
      METHODS: Eighty out of 938 patients with pectus excavatum operated on between
      2002 and 2013, 67 males and 13 females aged 11 to 49 years (mean: 19.2),
      underwent a complex surgical procedure. During surgery the Nuss procedure was
      usually performed first (one corrective bar was implanted in 35 patients and two
      bars were inserted in 45 patients). Because of the unsatisfactory cosmetic
      effect, additionally the Ravitch procedure was started. The bars were electively
      removed 3 years after the primary operation. RESULTS: No mortality was observed
      in the early postoperative period. Non-life-threatening and transient
      postoperative complications occurred in 44 (55%) patients. The most common was
      pleural effusion (21%), which in 50% of patients required pleural drainage. A
      satisfactory and stable correction effect was achieved in 88% of cases. Six of
      those patients required repeat surgery due to recurrence of deformity.
      CONCLUSIONS: A complex corrective procedure is a successful method of surgical
      treatment in patients with asymmetrical pectus excavatum and is characterized by
      satisfactory postoperative results. The use of corrective bars enhances the
      cosmetic effect. The frequency of early, mostly non-life-threatening
      postoperative complications after a complex procedure is insignificantly higher
      than that after the Nuss procedure.

PMID- 28747939
TI  - Diagnostic utility of biomarkers of left ventricular stress in patients with
      aortic stenosis and preserved left ventricular ejection fraction.
AB  - INTRODUCTION: Aortic stenosis (AS) is the most common acquired valvular heart
      disease. The early identification of patients with severe AS is crucial. NT
      proBNP is a well-known biomarker of pressure overload, and its role in patients
      with AS has been demonstrated in previous studies. Another, less well-known
      biomarker of pressure overload is sST2 protein, and its role in AS is unclear.
      AIM: To evaluate the utility of sST2 protein, NT-proBNP and selected clinical
      parameters in the assessment of degenerative AS severity in a population with
      preserved left ventricular ejection fraction (LVEF). MATERIAL AND METHODS: Sixty
      nine consecutive patients (mean age: 68.42 +/-12.58 years, 55.07% male) with
      symptomatic degenerative AS and preserved LVEF >= 45% were prospectively
      included. At enrollment complete transthoracic echocardiographic examination, ECG
      analysis, and standard laboratory tests including NT-proBNP were performed and
      blood samples for sST2 were obtained. RESULTS: There were 43 (62.32%) patients
      with severe AS. The multivariate stepwise linear regression models revealed that
      only systolic blood pressure (SBP), Sokolow-Lyon index and left ventricular end
      diastolic diameter (LVEDD) were independently associated with severe AS. Spearman
      correlation coefficients analysis showed no correlations between sST2 levels and
      a mild to moderate correlation between NT-proBNP concentration and parameters of
      AS severity. However, levels of NT-proBNP (p = 0.1857) and sST2 (p = 0.7851) did
      not differentiate patients according to severity of AS. CONCLUSIONS: In the study
      population with degenerative AS and preserved LVEF neither the NT-proBNP nor sST2
      concentrations can be used to differentiate patients according to the severity of
      AS.

PMID- 28747941
TI  - The prognostic value of carcinoembryonic antigen levels in blood and
      intraoperative pleural lavage fluid in non-small-cell lung cancer.
AB  - INTRODUCTION: There is no specific marker for lung cancer, but, in some lung
      cancer types, carcinoembryonic antigen (CEA) can reach high levels in the blood
      and pleural fluid. AIM: This study investigated the relationship of CEA levels in
      blood (CEAB) and intraoperative pleural lavage fluid (CEAP) in non-small-cell
      lung cancer (NSCLC) with the type, stage, and extent of lung cancer. MATERIAL AND
      METHODS: A total of 50 patients, who underwent surgery at our clinic due to NSCLC
      (group I) or benign lung pathology (group II), were assessed. For this
      prospectively designed study, 25 consecutive patients were included in each
      group, and their CEAB and CEAP levels were investigated. RESULTS: When the levels
      of CEAP were compared, the average value of group I (1.35 ng/ml) was
      significantly higher than the average value of group II (0.04 ng/ml) (p = 0.027).
      When CEA levels were examined separately, and average values were taken according
      to surgical pathology results, both CEAB and CEAP levels of adenocarcinoma
      patients were found to be higher than those of the other groups. This difference
      was only significant for the level of CEAP (p = 0.026). CONCLUSIONS: Although the
      average CEAB levels of patients with adenocarcinoma were higher than those of
      patients with other histopathological types, this difference was not
      statistically significant. However, we found that CEAP levels were significantly
      higher in patients with adenocarcinoma. These results have led us to consider
      that CEAP elevation is a more sensitive marker than the elevation of CEAB.

PMID- 28747943
TI  - The incidence of aspirin resistance in heart transplantation recipients.
AB  - INTRODUCTION: Coronary allograft vasculopathy can cause as many deaths as
      infections or rejection episodes within 3 years following heart transplantation.
      AIM: To compare the aspirin resistance rate in an allograft heart transplantation
      population and in a control group by laboratory tests including the Aspirin
      Resistant Patients Identification Test (ASPItest). MATERIAL AND METHODS: A total
      of 24 heart recipients (20 men and 4 women) at a mean age of 48 +/-13 years who
      underwent routine clinical follow-up were consecutively enrolled in group 1. The
      control group consisted of 24 patients (19 men and 5 women) at a mean age of 64
      +/-7 years waiting for coronary artery bypass grafting in our department. All
      patients were treated with a standard dose of 75 mg aspirin (ASA) daily. RESULTS:
      Aspirin resistance was evaluated by the Multiplate platelet function test. The
      ASPItest revealed a mean value of 27 +/-22 U in the transplant group. Results
      above 30 U were obtained in 8 (34%) patients, with a mean value of 50.3 +/-20.6
      U, indicating aspirin resistance. In the control group ASPItest results above 30
      U were obtained in 5 (20%) patients, with a mean value of 43.3 +/-6.4 U.
      CONCLUSIONS: There is a high incidence (34% vs. 20%, NS) of ASA resistance in
      heart transplantation recipients and in the general population, respectively.

PMID- 28747944
TI  - Impact of post-hospital cardiac rehabilitation on the quality of life of patients
      after surgical treatment for coronary artery disease.
AB  - INTRODUCTION: The quality of life of cardiovascular patients is worse than that
      of healthy individuals. Pain, dyspnea, and fatigue impair daily activities, which
      in turn leads to decreased life satisfaction and emotional deterioration. The
      objective of comprehensive treatment, including early rehabilitation, is to
      reduce the risk of complications, progression, and recurrence of the disease, as
      well as to restore, maintain, or improve all aspects of the patient's quality of
      life to the greatest extent possible. AIM: To assess the quality of life of
      patients who underwent surgical treatment for coronary artery disease and
      completed the second phase of cardiac rehabilitation. MATERIAL AND METHODS: The
      study enrolled 100 patients undergoing early cardiac rehabilitation in stationary
      conditions after coronary artery bypass grafting. The group included 21 women and
      79 men; their age ranged from 40 to 75 years. The study employed a questionnaire
      of our own design. RESULTS: Post-hospital cardiac rehabilitation resulted in
      quality of life improvements, especially with regard to psychological aspects,
      reducing the occurrence of anxiety from 44% to 21%. In addition, the
      rehabilitation program reduced the occurrence of subjective ailments such as
      chest pain (from 68% to 10%), fatigue (from 40% to 33%), and dyspnea (from 50% to
      12%). CONCLUSIONS: Despite the achievement of quality of life improvements among
      patients after surgery coronary artery by-pass grafting and early cardiac
      rehabilitation, the result is not fully satisfactory. Systematic treatment and
      education should be continued to further improve the health of patients.

PMID- 28747945
TI  - The impact of type 2 diabetes mellitus on prognosis in patients with non-ST
      elevation myocardial infarction.
AB  - Type 2 diabetes (T2D) is a recognized risk factor for acute coronary syndromes.
      There is currently no consensus concerning the intensification of
      antihyperglycemic treatment. According to the available guidelines, it seems that
      the goal is to achieve glycated hemoglobin (HbA1c) levels below 7% and avoid
      hypoglycemia. The choice of a revascularization method is influenced by many
      factors, such as the anatomy of the coronary arteries, severity of
      atherosclerosis, anatomical location of lesions, and presence of comorbidities.
      However, in non-ST elevation myocardial infarction, determining the culprit
      lesion is often difficult based on ECG or angiography. Experts recommend coronary
      artery bypass grafting (CABG) in patients with type 2 diabetes and multivessel or
      complex (SYNTAX score exceeding 22 points) coronary artery disease in order to
      improve survival. Percutaneous coronary intervention should be considered as an
      alternative to CABG to control symptoms in patients with type 2 diabetes and less
      complex forms of the disease (i.e., SYNTAX score of 22 or lower).

PMID- 28747946
TI  - Antiplatelet treatment in the primary prophylaxis of cardiovascular disease in
      patients with arterial hypertension.
AB  - The benefits of using acetylsalicylic acid (ASA) in the primary prophylaxis of
      cardiovascular diseases may only slightly exceed the risk of serious bleeding.
      This warrants the search for alternative, safer preparations with antiaggregatory
      properties, which could be used in patients burdened with cardiovascular risk
      factors. Antiaggregatory compounds identified in water-soluble tomato extract
      include nucleosides, flavonoids, and phenolic acids. The action of standardized
      tomato extract is multidirectional, reversible, and weaker in comparison to ASA.
      The European Food Safety Authority (EFSA) has approved this preparation as a
      dietary agent with antiaggregatory properties. The use of standardized tomato
      extract appears beneficial in arterial hypertension patients with low or moderate
      cardiovascular risk and in patients in whom good pressure control cannot be
      achieved.

PMID- 28747947
TI  - A foreign body mimicking tracheal stenosis.

PMID- 28747948
TI  - A huge primary pleomorphic liposarcoma of the left atrium.

PMID- 28747949
TI  - Coexistence of partial anomalous pulmonary venous return and cardiac coronary
      anomaly - the role of preoperative imaging.

PMID- 28747950
TI  - Pleural empyema caused by incarceration and perforation of the stomach wall
      discovered several years later after thoracic trauma.

PMID- 28747951
TI  - Esophageal diverticulosis.

PMID- 28747952
TI  - Human Permanent Ectoparasites; Recent Advances on Biology and Clinical
      Significance of Demodex Mites: Narrative Review Article.
AB  - BACKGROUND: Demodex is a genus of mites living predominantly in mammalian
      pilosebaceous units. They are commonly detected in the skin of face, with
      increasing numbers in inflammatory lesions. Causation between Demodex mites and
      inflammatory diseases, such as rosacea, blepharitis, perioral and seborrhoeic
      dermatitis or chalazion, is controversially discussed. Clinical observations
      indicate a primary form of human Demodex infection. The aim of this review was to
      highlight the biological aspects of Demodex infestation and point out directions
      for the future research. METHODS: We conducted a broad review based on the
      electronic database sources such as MEDLINE, PubMed and Scopus with regard to the
      characteristics of the Demodex species, methods of examination and worldwide
      epidemiology, molecular studies and its role in the complex human ecosystem.
      RESULTS: Demodex mites are organisms with a worldwide importance as they act in
      indicating several dermatoses, under certain conditions. However, correlations
      between Demodex and other parasites or microorganisms occupying one host, as well
      as interactions between these arachnids and its symbiotic bacteria should be
      considered. There are few methods of human mites' examination depending on
      purpose of the study. Nevertheless, paying attention must be needed as
      polymorphism of Demodex species has been reported. CONCLUSION: Overall, the
      present review will focus on different aspects of Demodex mites' biology and
      significance of these arachnids in human's health.

PMID- 28747953
TI  - Current Epidemiological Data on Asthma Management in South Korea from Qualitative
      Assessment of Asthma Management by Health Insurance Review and Assessment Service
      (HIRA).
AB  - Since 2015, the Health Insurance Review and Assessment Service (HIRA) has
      performed annual qualitative assessments of asthma management provided by all
      medical institutions that care for asthma patients in Korea. According to the
      third report of qualitative assessment of asthma management in 2017, the
      assessment appears to have contributed to improving the quality of asthma care
      provided by medical institutions, especially primary clinics. However, there is
      still a gap between the ideal goals of asthma management and actual health care
      policies/regulations in real clinical settings, which leads to the state of
      standstill with respect to the quality of asthma management despite considerable
      efforts such as the qualitative assessment of asthma management by national
      agencies such as the HIRA. At this point, a harmonized approach is needed to
      raise the level of asthma management among several components including medical
      policies, efforts of academic associations such as education and distribution of
      the guideline for management, and reliable financial support by the government.

PMID- 28747954
TI  - Recent Trends in the Prevalence of Chronic Obstructive Pulmonary Disease in
      Korea.
AB  - Chronic obstructive pulmonary disease (COPD) had been considered the only major
      disease that is continuing to increase in prevalence. There were a few studies
      about the change of the prevalence of COPD, which showed the prevalence of COPD
      did not increase. In this review, we report on the trends in the prevalence of
      COPD in Korea using the data from Korea National Health and Nutrition Examination
      Survey (KNHANES). The prevalence of COPD in 2015 was 13.4% (male, 21.6%; female,
      5.8%). The prevalence of COPD did not change much, which ranged from 13.1% to
      14.6% during the period from 2010 to 2015. Among the subjects found to have COPD
      by spirometry, only 2.8% had been diagnosed as COPD by physicians during the
      period from 2011 and 2015. In conclusion, the prevalence of COPD did not change
      significantly during the period from 2010 to 2015. And most COPD patients still
      had not been diagnosed by physicians and consequently had not been treated
      appropriately.

PMID- 28747955
TI  - Summary of the Chronic Obstructive Pulmonary Disease Clinical Practice Guideline
      Revised in 2014 by the Korean Academy of Tuberculosis and Respiratory Disease.
AB  - Chronic obstructive pulmonary disease (COPD) results in high morbidity and
      mortality among patients both domestically and globally. The Korean clinical
      practice guideline for COPD was revised in 2014. It was drafted by the members of
      the Korean Academy of Tuberculosis and Respiratory Diseases, as well as
      participating members of the Health Insurance Review and Assessment Service,
      Korean Physicians' Association, and Korea Respiration Trouble Association. This
      revised guideline covers a wide range of topics, including the epidemiology,
      diagnosis, assessment, monitoring, management, exacerbation, and comorbidities of
      COPD in Korea. We drafted a guideline on COPD management by performing systematic
      reviews on the topic of management with the help of a meta-analysis expert. We
      expect this guideline will be helpful medical doctors treating patients with
      respiratory conditions, other health care professionals, and government personnel
      in South Korea.

PMID- 28747956
TI  - Evaluation of Appropriate Management of Chronic Obstructive Pulmonary Disease in
      Korea: Based on Health Insurance Review and Assessment Service (HIRA) Claims.
AB  - Chronic obstructive pulmonary disease (COPD) is an ambulatory care-sensitive
      condition, and effective treatment of outpatients can prevent worsening of the
      illness and hospitalization. Current COPD guidelines provide appropriate guidance
      for the diagnosis and treatment of patients with COPD. In fact, it has been shown
      that when appropriate guidance and treatment are performed, the morbidity and
      mortality rates of COPD patients are reduced. However, there is a gap between the
      clinical guidelines and the actual clinical treatment. Therefore, the Health
      Insurance Review and Assessment Service (HIRA) conducted an evaluation of the
      adequacy of COPD diagnosis and treatment using the Claims Database of HIRA. This
      review provides a summary of the COPD adequacy assessment results reported by the
      HIRA and some brief comments on the results.

PMID- 28747957
TI  - ACN9 Regulates the Inflammatory Responses in Human Bronchial Epithelial Cells.
AB  - BACKGROUND: Airway epithelial cells are the first line of defense, against
      pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium
      (Cd), resulting in airway inflammation, is assumed to be directly involved in
      tissue injury, linked to the development of lung cancer, and chronic obstructive
      pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a
      potential candidate gene for COPD, and identified significant interaction with
      smoking, based on genetic studies. However, the role of ACN9 in the inflammatory
      response, in the airway cells, has not yet been reported. METHODS: We first
      checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ
      hybridization, and immunohistochemistry. Gene expression profiling in bronchial
      epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further
      tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced
      production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized
      in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to
      differential expression of 216 genes. Pathways of sensory perception to chemical
      stimuli, and cell surface receptor-linked signal transduction, were significantly
      enriched. ACN9 silencing, further increased the expression of proinflammatory
      cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that
      ACN9 may have a role, in the inflammatory response in the airway.

PMID- 28747958
TI  - The Role of N-Acetyl Transferases on Isoniazid Resistance from Mycobacterium
      tuberculosis and Human: An In Silico Approach.
AB  - BACKGROUND: N-acetyl transferase (NAT) inactivates the pro-drug isoniazid (INH)
      to N-acetyl INH through a process of acetylation, and confers low-level
      resistance to INH in Mycobacterium tuberculosis (MTB). Similar to NAT of MTB,
      NAT2 in humans performs the same function of acetylation. Rapid acetylators, may
      not respond to INH treatment efficiently, and could be a potential risk factor,
      for the development of INH resistance in humans. METHODS: To understand the
      contribution of NAT of MTB and NAT2 of humans in developing INH resistance using
      in silico approaches, in this study, the wild type (WT) and mutant (MT)-NATs of
      MTB, and humans, were modeled and docked, with substrates and product (acetyl
      CoA, INH, and acetyl INH). The MT models were built, using templates 4BGF of MTB,
      and 2PFR of humans. RESULTS: On the basis of docking results of MTB-NAT, it can
      be suggested that in comparison to the WT, binding affinity of MT-G207R, was
      found to be lower with acetyl CoA, and higher with acetyl-INH and INH. In case of
      MT-NAT2 from humans, the pattern of score with respect to acetyl CoA and acetyl
      INH, was similar to MT-NAT of MTB, but revealed a decrease in INH score.
      CONCLUSION: In MTB, MT-NAT revealed high affinity towards acetyl-INH, which can
      be interpreted as increased formation of acetyl-INH, and therefore, may lead to
      INH resistance through inactivation of INH. Similarly, in MT-NAT2 (rapid
      acetylators), acetylation occurs rapidly, serving as a possible risk factor for
      developing INH resistance in humans.

PMID- 28747959
TI  - Effect of Prophylactic Use of Silymarin on Anti-tuberculosis Drugs Induced
      Hepatotoxicity.
AB  - BACKGROUND: The first line of anti-tuberculosis (TB) drugs are the most effective
      standard of drugs for TB. However, the use of these drugs is associated with
      hepatotoxicity. Silymarin has protective effects against hepatotoxicity of anti
      TB drugs in animal models. This study aims to investigate the protective effect
      of silymarin on hepatotoxicity caused by anti-TB drugs. METHODS: This is a
      prospective, randomized, double-blind and placebo-controlled study. Patients were
      eligible if they were 20 years of age or order and started the first-line anti
      tuberculosis drugs. Eligible patients were randomized for receiving silymarin or
      a placebo for the first 4 weeks. The primary outcome was the proportion of
      patients who showed elevated serum liver enzymes more than 3 times the upper
      normal limit (UNL) or total bilirubin (TBil) > 2* UNL within the first 8 weeks of
      anti-TB treatment. RESULTS: We enrolled a total of 121 patients who silymarin or
      a placebo to start their anti-TB treatment, for the first 8 weeks. The
      proportions of elevated serum liver enzymes more than 3 times of UNL at week 2,
      week 4, and week 8 did not show any significant difference between the silymarin
      and placebo groups, at 0% versus 3.6% (p>0.999); 4.4% versus 3.6% (p>0.999); and
      8.7% versus 10.8% (p=0.630), respectively. However, patients with TBil >2* ULN at
      week 8 were significantly low in the silymarin group (0% versus 8.7%, p=0.043).
      CONCLUSION: Our findings did not show silymarin had any significant preventive
      effect on the hepatotoxicity of anti-TB drugs.

PMID- 28747960
TI  - Frequency and Type of Disputed rpoB Mutations in Mycobacterium tuberculosis
      Isolates from South Korea.
AB  - BACKGROUND: A disputed rpoB mutation is a specific type of rpoB mutation that can
      cause low-level resistances to rifampin (RIF). Here, we aimed to assess the
      frequency and types of disputed rpoB mutations in Mycobacterium tuberculosis
      isolates from South Korea. METHODS: Between August 2009 and December 2015, 130
      patients exhibited RIF resistance on the MTBDRplus assay at Asan Medical Center.
      Among these cases, we identified the strains with disputed rpoB mutation by rpoB
      sequencing analysis, as well as among the M. tuberculosis strains from the
      International Tuberculosis Research Center (ITRC). RESULTS: Among our cases,
      disputed rpoB mutations led to RIF resistance in at least 6.9% (9/130) of the
      strains that also exhibited RIF resistance on the MTBDRplus assay. Moreover, at
      the ITRC, sequencing of the rpoB gene of 170 strains with the rpoB mutation
      indicated that 23 strains (13.5%) had the disputed mutations. By combining the
      findings from the 32 strains from our center and the ITRC, we identified the type
      of disputed rpoB mutation as follows: CTG511CCG (L511P, n=8), GAC516TAC (D516Y,
      n=8), CTG533CCG (L533P, n=8), CAC526CTC (H526L, n=4), CAC526AAC (H526N, n=3), and
      ATG515GTG (M515V, n=1). CONCLUSION: Disputed rpoB mutations do not seem to be
      rare among the strains exhibiting RIF resistance in South Korea.

PMID- 28747961
TI  - Determinants of Nicotine Dependence in Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: Smoking cessation is the most powerful intervention to modify
      progress of chronic obstructive pulmonary disease (COPD), and nicotine dependence
      is one of the most important determinants of success or failure in smoking
      cessation. We evaluated nicotine dependence status and investigated factors
      associated with moderate to high nicotine dependence in patients with COPD.
      METHODS: We included 53 current smokers with COPD in the Korean Obstructive Lung
      Disease II cohort enrolled between January 2014 and March 2016. Nicotine
      dependence was measured by using Fagerstrom test for nicotine dependence (FTND).
      Cognitive function was assessed by Korean version of Montreal Cognitive
      Assessment. RESULTS: The median FTND score was 3, and 32 patients (60%) had
      moderate to high nicotine dependence. The median smoking amount was 44 pack
      years, which was not related to nicotine dependence. Multiple logistic regression
      analysis revealed that high education status (odds ratio, 1.286; 95% confidence
      interval, 1.036-1.596; p=0.023), age <70 (odds ratio, 6.407; 95% confidence
      interval, 1.376-29.830; p=0.018), and mild to moderate airflow obstruction (odds
      ratio, 6.969; 95% confidence interval, 1.388-34.998; p=0.018) were related to
      moderate to high nicotine dependence. CONCLUSION: Nicotine dependence does not
      correlate with smoking amount, but with education level, age, and severity of
      airflow obstruction. Physicians should provide different strategies of smoking
      cessation intervention for current smokers with COPD according to their education
      levels, age, and severity of airflow obstruction.

PMID- 28747962
TI  - Factors Related to the Diagnostic Yield of Flexible Bronchoscopy without Guidance
      in Bronchoscopically Invisible Peripheral Lung Lesions.
AB  - BACKGROUND: We aimed to analyze the factors predicting the diagnostic performance
      of flexible bronchoscopy without guidance in peripheral lung lesions that are
      endoscopically invisible. METHODS: This was a retrospective study conducted in
      St. Paul's Hospital, The Catholic University of Korea, between January 2007 and
      March 2013. We included all patients who received bronchoscopy during this
      period. The analyzed variables were age, sex, the etiology of the lesion, lesion
      size, distance from the pleura, and presence of the bronchus sign. We used
      multiple logistic regression analysis to identify the significant independent
      factors associated with diagnostic yield. RESULTS: We included 151 patients in
      this study. The overall diagnostic yield was 58.3%. The sensitivity was 43.2% for
      malignant disease and 78.1% for benign disease. The benign lung lesions
      (p<0.001), lesion size (p=0.015), presence of the exposed type of bronchus sign
      (p<0.001), and presence of cavitary lung lesions (p=0.005) were factors
      influencing the yield of flexible bronchoscopy by univariate analysis. In a
      multivariate logistic regression analysis, the exposed type of bronchus sign and
      benign lung lesions were independent predicting factors (odds ratio [OR]: 27.95;
      95% confidence interval [CI], 7.56-103.32; p<0.001 and OR, 4.91; 95% CI, 1.76
      13.72; p=0.002). CONCLUSION: The presence of the exposed type of bronchus sign
      and benign lung lesions are determining factors of the diagnostic yield in
      flexible bronchoscopy in evaluating peripheral lesions that are not
      endoscopically visible.

PMID- 28747963
TI  - Review of Sarcoidosis in a Province of South Korea from 1996 to 2014.
AB  - BACKGROUND: Since the introduction of endobronchial ultrasound (EBUS)-guided
      transbronchial needle aspiration (TBNA) of mediastinal lymph nodes, the incidence
      of histopathologically-confirmed sarcoidosis has increased. METHODS: The
      electronic medical records of Chonnam National University (CNU) Hospital and CNU
      Hwasun Hospital (CNUHH) were searched for confirmed cases of sarcoidosis
      diagnosed between 1996 and 2014. Cases were selected using a combination of
      clinical, radiological, and pathological evidence. Of 115 cases with the relevant
      disease codes, 16 cases were excluded, as they had not been confirmed
      pathologically or had no definitive clinical features of sarcoidosis. RESULTS:
      Among 99 cases of confirmed sarcoidosis, only nine patients were diagnosed with
      sarcoidosis before 2008; the rest were diagnosed from 2008 onward, after the
      introduction of EBUS-TBNA. EBUS-TBNA was used in 75.8% of patients, open surgical
      biopsy in 13.2%, and mediastinoscopic biopsy in 5.1%. At the time of diagnosis,
      42.4% of sarcoidosis cases were at stage I, 55.6% at stage II, and 2% at stage
      III. Spontaneous remission of sarcoidosis was observed in 33.3% of cases, and
      stable disease in 37.4%; systemic steroid treatment was initiated in 23.2% of
      cases. Of the patients treated with systemic steroids, 69.6% showed improvement.
      The median duration of steroid treatment was 5 months. CONCLUSION: Following the
      introduction of EBUS-TBNA, the number of newly diagnosed sarcoidosis patients has
      increased. Clinical features of sarcoidosis were similar to those previously
      reported. Spontaneous remission occurred in about one-third of patients, while
      one-fourth of patients required systemic steroid treatment.

PMID- 28747964
TI  - Effect of Preadmission Metformin Use on Clinical Outcome of Acute Respiratory
      Distress Syndrome among Critically Ill Patients with Diabetes.
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) is related to high
      mortality and morbidity. There are no proven therapeutic measures however, to
      improve the clinical course of ARDS, except using low tidal volume ventilation.
      Metformin is known to have pleiotropic effects including anti-inflammatory
      activity. We hypothesized that pre-admission metformin might alter the progress
      of ARDS among intensive care unit (ICU) patients with diabetes mellitus (DM).
      METHODS: We performed a retrospective cohort study from January 1, 2005, to April
      30, 2005 of patients who were admitted to the medical ICU at Seoul National
      University Hospital because of ARDS, and reviewed ARDS patients with DM.
      Metformin use was defined as prescribed within 3-month pre-admission. RESULTS: Of
      558 patients diagnosed with ARDS, 128 (23.3%) patients had diabetes and 33
      patients were treated with metformin monotherapy or in combination with other
      antidiabetic medications. Demographic characteristics, cause of ARDS, and
      comorbid conditions (except chronic kidney disease) were not different between
      metformin users and nonusers. Several severity indexes of ARDS were similar in
      both groups. The 30-day mortality was 42.42% in metformin users and 55.32% in
      metformin nonusers. On multivariable regression analysis, use of metformin was
      not significantly related to a reduced 30-day mortality (adjusted beta
      coefficient, -0.19; 95% confidence interval, -1.76 to 1.39; p=0.816). Propensity
      score-matched analyses showed similar results. CONCLUSION: Pre-admission
      metformin use was not associated with reduced 30-day mortality among ARDS
      patients with DM in our medical ICU.

PMID- 28747966
TI  - Pharmacotherapy for Acute Respiratory Distress Syndrome: Limited Success to Date.

PMID- 28747965
TI  - Systemic White Blood Cell Count as a Biomarker Associated with Severity of
      Chronic Obstructive Lung Disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD), is a chronic
      inflammatory disorder. We evaluated whether white blood cell (WBC) count, is
      associated with the severity of COPD, independent of other inflammatory
      conditions, such as metabolic syndrome. METHODS: The WBC counts were compared
      between 1227 COPD patients and 8679 non-COPD adults older than 40. The
      relationships between the WBC count, lung function, and symptoms score in COPD
      patients, were determined, using general linear regression analyses. RESULTS: The
      WBC count was negatively associated with forced vital capacity (FVC, L), FVC (%
      predicted), forced expiry volume in one second (FEV1, L), and FEV1 (% predicted)
      in COPD patients. Additionally, the WBC count was independently associated with
      the quality of life measure, by EQ5D-index score. However, this relationship
      between WBC count, and disease severity, was not significant in current smokers,
      because of the confounding effect of smoking, on the WBC count. CONCLUSION: The
      WBC count is associated with current smoking status and COPD severity, and a risk
      factor for poor lung function, and quality of life, especially in non-currently
      smoking COPD patients. The WBC count can be used, as an easily measurable COPD
      biomarker.

PMID- 28747967
TI  - Systemic White Blood Cell Count as a Biomarker for Chronic Obstructive Pulmonary
      Disease: Utility and Limitations.

PMID- 28747968
TI  - Quinolone susceptibility and genetic characterization of Salmonella enterica
      subsp. enterica isolated from pet turtles.
AB  - Turtle-borne Salmonella enterica owns significance as a leading cause in human
      salmonellosis. The current study aimed to determine the quinolone susceptibility
      and the genetic characteristics of 21 strains of S. enterica subsp. enterica
      isolated from pet turtles. Susceptibility of four antimicrobials including
      nalidixic acid, ciprofloxacin, ofloxacin, and levofloxacin was examined in disk
      diffusion and MIC tests where the majority of the isolates were susceptible to
      all tested quinolones. In genetic characterization, none of the isolates were
      positive for qnr or aac(6')-Ib genes and no any target site mutations could be
      detected in gyrA, gyrB, and parC quinolone resistance determining regions (QRDR).
      In addition, neighbor-joining phylogenetic tree derived using gyrA gene sequences
      exhibited two distinct clads comprising; first, current study isolates, and
      second, quinolone-resistant isolates of human and animal origin. All results
      suggest that studied strains of S. enterica subsp. enterica isolated from pet
      turtles are susceptible to quinolones and genetically more conserved with regards
      to gyrA gene region.

PMID- 28747969
TI  - Hepatotoxicity and nephrotoxicity of saponin-enriched extract of Asparagus
      cochinchinensis in ICR mice.
AB  - The inhibitory effects of Asparagus cochinchinensis against inflammatory response
      induced by lipopolysaccharide (LPS), substance P and phthalic anhydride (PA)
      treatment were recently reported for some cell lines and animal models. To
      evaluate the hepatotoxicity and nephrotoxicity of A. cochinchinensis toward the
      livers and kidneys of ICR mice, alterations in related markers including body
      weight, organ weight, urine composition, liver pathology and kidney pathology
      were analyzed in male and female ICR mice after oral administration of 150, 300
      and 600 mg/kg body weight/day saponin-enriched extract of A. cochinchinensis
      (SEAC) for 14 days. The saponin, total flavonoid and total phenol levels were
      found to be 57.2, 88.5 and 102.1 mg/g in SEAC, respectively, and the scavenging
      activity of SEAC gradually increased in a dose-dependent manner. Moreover, body
      and organ weight, clinical phenotypes, urine parameters and mice mortality did
      not differ between the vehicle and SEAC treated group. Furthermore, no
      significant alterations were measured in alkaline phosphatase (ALP), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase
      (LDH), blood urea nitrogen (BUN) and the serum creatinine (Cr) in the SEAC
      treated group relative to the vehicle treated group. Moreover, the specific
      pathological features induced by most toxic compounds were not observed upon
      liver and kidney histological analysis. Overall, the results of the present study
      suggest that SEAC does not induce any specific toxicity in the livers and kidneys
      of male and female ICR mice at doses of 600 mg/kg body weight/day.

PMID- 28747970
TI  - Reproductive performance of genetically engineered mice housed in different
      housing systems.
AB  - The genetically engineered mice require special husbandry care and are mainly
      housed in Individually Ventilated Cage (IVC) systems and Static Micro Isolator
      Cages (SMIC) to minimize the risk for spreading undesirable microorganisms.
      However, the static micro isolation cage housing like SMIC are being replaced
      with IVC systems in many facilities due to a number of benefits like a higher
      density housing in limited space, better protection from biohazards and allergens
      and decreased work load due to decreased frequency of cage changing required in
      this system. The purpose of this study was to examine the reproductive
      performance of genetically engineered mice housed in individually ventilated
      cages (IVC) and Static Micro Isolator Cages (SMIC). When the B6C3-Tg (APPswe,
      PSEN1dE9) 85Dbo/Mmjax transgenic mice were housed in these two housing systems,
      the number of litters per dam, number of pups born per dam and number of pups
      weaned per dam were found to be slightly higher in the IVC as compared to the
      SMIC but the difference was not significant (P<0.05). In case of Growth
      Associated Protein 43 (GAP-43) knockout mice, the number of litters born per dam
      and the number of pups born per dam were marginally higher in the IVC as compared
      to those housed in SMIC but the difference was not significant (P<0.05). Only the
      number of pups weaned per dam were found to be significantly higher as compared
      to those housed in the SMIC system at P<0.05.

PMID- 28747971
TI  - Pine bark extract (Pycnogenol(r)) suppresses cigarette smoke-induced fibrotic
      response via transforming growth factor-beta1/Smad family member 2/3 signaling.
AB  - Chronic obstructive pulmonary diseases (COPD) is an important disease featured as
      intense inflammation, protease imbalance, and air flow limitation and mainly
      induced by cigarette smoke (CS). In present study, we explored the effects of
      Pycnogenol(r) (PYC, pine bark extract) on pulmonary fibrosis caused by
      CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on
      day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4
      weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by
      oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells
      and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage
      fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS
      exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming
      growth factor-beta1 (TGF-beta1) expression and Smad family member 2/3 (Smad 2/3)
      phosphorylation were effectively suppressed by PYC treatment. PYC markedly
      reduced the collagen deposition caused by CS+LPS exposure, which was closely
      involved in TGF-beta1/Smad 2/3 signaling, which is associated with pulmonary
      fibrotic change. These findings suggest that treatment with PYC could be a
      therapeutic strategy for controlling COPD progression.

PMID- 28747972
TI  - Antimicrobial property of lemongrass (Cymbopogon citratus) oil against pathogenic
      bacteria isolated from pet turtles.
AB  - The usage of essential oils as antimicrobial agents is gaining attention.
      Besides, pet turtles were known to harbor a range of pathogenic bacteria while
      the turtle keeping is a growing trend worldwide.The current study examined the
      antimicrobial activity of lemon grass oil (LGO) against seven species of Gram
      negative bacteria namely; Aeromonas hydrophila, A. caviae, Citrobacter freundii,
      Salmonella enterica, Edwardsiella tarda, Pseudomonas aeruginosa, and Proteus
      mirabilis isolated from three popular species of pet turtles. Along with the
      results of disc diffusion, minimum inhibitory and minimum bactericidal
      concentration (MIC and MBC) tests, LGO was detected as effective against 6
      species of bacteria excluding P. aeruginosa. MIC of LGO for the strains except P.
      aeruginosa ranged from 0.016 to 0.5% (V/V). The lowest MIC recorded in the E.
      tarda strain followed by A. hydrophilla, C. freundii, P. mirabilis, and S.
      enterica. Interestingly, all the bacterial species except E. tarda were showing
      high multiple antimicrobial resistance (MAR) index values ranging from 0.36 to
      0.91 upon the 11 antibiotics tested although they were sensitive to LGO.

PMID- 28747973
TI  - Effect of ionizing radiation at low dose on transgenerational carcinogenesis by
      epigenetic regulation.
AB  - The objective of this study was to determine the effect of ionizing radiation
      (IR) exposure of parents on carcinogenesis of the next generation focusing on the
      epigenetic perspective to clarify the relationship between radiation dose and
      carcinogenesis in F1 generation SD rats. F1 generations from pregnant rats (F0)
      who were exposed to gamma rays were divided into three groups according to the
      dose of radiation: 10 rad, 30 rad, and untreated. They were intraperitoneally
      injected with 50 mg/kg of diethylnitrosamine (DEN). Carcinogenesis was analyzed
      by examining expression levels of tumor suppressor genes (TSG) and other related
      genes by methylation-specific polymerase chain reaction (MSP). DNA methylation in
      liver tissues was evaluated to discern epigenetic regulation of transgenerational
      carcinogenesis vulnerability following IR exposure. Numerous studies have proved
      that transcriptional inactivation due to hypermethylation of TSG preceded
      carcinogenesis. Results of this study revealed hypermethylation of tumor
      suppressor gene SOCS1 in group treated with 30 rad. In addition, genes related to
      DNA damage response pathway (GSTP1, ATM, DGKA, PARP1, and SIRT6) were
      epigenetically inactivated in all DEN treated groups. In the case of proto
      oncogene c-Myc, DNA hypermethylation was identified in the group with low dose of
      IR (10 rad). Results of this study indicated that each TSG had different
      radiation threshold level (dose-independent way) and DEN treatment could affect
      DNA methylation profile irrelevant of ionizing radiation dose.

PMID- 28747974
TI  - Hyperglycemia decreases preoxiredoxin-2 expression in a middle cerebral artery
      occlusion model.
AB  - Diabetes is a major risk factor for stroke and is also associated with worsened
      outcomes following a stroke. Peroxiredoxin-2 exerts potent neuroprotective
      effects against oxidative stress. In the present study, we identified altered
      peroxiredoxin-2 expression in an ischemic stroke model under hyperglycemic
      conditions. Adult male rats were administrated streptozotocin (40 mg/kg) via
      intraperitoneal injection to induce diabetes. Middle cerebral artery occlusion
      (MCAO) was induced surgically 4 weeks after streptozotocin treatment and cerebral
      cortex tissues were isolated 24 hours after MCAO. Peroxiredoxin-2 expression was
      evaluated in the cerebral cortex of MCAO-operated animals using a proteomics
      approach, and was found to be decreased. In addition, the reduction in
      peroxiredoxin-2 levels was more severe in cerebral ischemia with diabetes
      compared to animals without diabetes. Reverse-transcriptase PCR and Western blot
      analyses confirmed the significantly reduced peroxiredoxin-2 expression in MCAO
      operated animals under hyperglycemic conditions. It is an accepted fact that
      peroxiredoxin-2 has antioxidative activity against ischemic injury. Thus, the
      findings of this study suggest that a more severe reduction in peroxiredoxin-2
      under hyperglycemic conditions leads to worsened brain damage during cerebral
      ischemia with diabetes.

PMID- 28747975
TI  - Blood flow-improving activity of methyl jasmonate-treated adventitious roots of
      mountain ginseng.
AB  - Ginsenosides from Panax ginseng are well known for their diverse pharmacological
      effects including antithrombotic activity. Since adventitious roots of mountain
      ginseng (ARMG) also contain various ginsenosides, blood flow-improving effects of
      the dried powder and extract of ARMG were investigated. Rats were orally
      administered with dried powder (PARMG) or ethanol extract (EARMG) of ARMG (125,
      250 or 500 mg/kg) or aspirin (30 mg/kg, a reference control) for 3 weeks. Forty
      min after the final administration, carotid arterial thrombosis was induced by
      applying a 70% FeCl3-soaked filter paper outside the arterial wall for 5 min, and
      the blood flow was monitored with a laser Doppler probe. Both PARMG and EARMG
      delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling
      the occlusion time at high doses. In mechanism studies, a high concentration of
      EARMG inhibited platelet aggregation induced by collagen in vitro. In addition,
      EARMG improved the blood lipid profiles, decreasing triglyceride and cholesterol
      levels. Although additional action mechanisms remain to be clarified, it is
      suggested that ARMG containing high amount of ginsenosides such as Rg3 improves
      blood flow not only by inhibiting oxidative thrombosis, but also by modifying
      blood lipid profiles.

PMID- 28747848
TI  - Search for squarks and gluinos in events with hadronically decaying tau leptons,
      jets and missing transverse momentum in proton-proton collisions at [Formula: see
      text] TeV recorded with the ATLAS detector.
AB  - A search for supersymmetry in events with large missing transverse momentum,
      jets, and at least one hadronically decaying tau lepton has been performed using
      3.2 fb[Formula: see text] of proton-proton collision data at [Formula: see text]
      recorded by the ATLAS detector at the Large Hadron Collider in 2015. Two
      exclusive final states are considered, with either exactly one or at least two
      tau leptons. No excess over the Standard Model prediction is observed in the
      data. Results are interpreted in the context of gauge-mediated supersymmetry
      breaking and a simplified model of gluino pair production with tau-rich cascade
      decays, substantially improving on previous limits. In the GMSB model considered,
      supersymmetry-breaking scale ([Formula: see text]) values below [Formula: see
      text] are excluded at the 95% confidence level, corresponding to gluino masses
      below [Formula: see text]. For large values of [Formula: see text], values of
      [Formula: see text] up to [Formula: see text] and gluino masses up to [Formula:
      see text] are excluded. In the simplified model, gluino masses are excluded up to
      [Formula: see text] for neutralino masses around [Formula: see text]. Neutralino
      masses below [Formula: see text] are excluded for all gluino masses between 800
      and [Formula: see text], while the strongest exclusion of [Formula: see text] is
      achieved for gluino masses around [Formula: see text].

PMID- 28747976
TI  - Immunohistochemical localization of glucose transporter 1 and 3 in the scrotal
      and abdominal testes of a dog.
AB  - Glucose is essential for testicular function; the uptake of carbohydrate-derived
      glucose by cells is mediated by glucose transporters (GLUTs). In the present
      study, we investigated the activity of GLUT1 and GLUT3, the two main isoforms of
      GLUTs found in testes, in the left scrotal and right abdominal testes of a German
      Shepherd dog. Immunohistochemical analysis showed that GLUT1 immunoreactivity was
      absent in the scrotal and abdominal testes. In contrast, weak to moderate GLUT3
      immunoreactivity was observed in mature spermatocytes as well as spermatids in
      the scrotal testis. In the abdominal testis, relatively strong GLUT3
      immunoreactivity was detected in Leydig cells only and was absent in mature
      spermatocytes and spermatids. GLUT3 immunoreactivity was significantly decreased
      in the tubular region of abdominal testis and significantly increased in the
      extra-tubular (interstitial) region of abdominal testis compared to observations
      in the each region of scrotal testis, respectively. These results suggest that
      GLUT3 is the major glucose transporter in the testes and that abdominal testes
      may increase the uptake of glucose into interstitial areas, leading to an
      increased risk of developing cancer.

PMID- 28747978
TI  - Comparative study of the immunological characteristics of three different
      C57BL/6N mouse substrains.
AB  - Inbred mice, a systematically developed homogeneous animal, have been developed
      to maintain experimental reproducibility and to minimize experimental variables
      in animal-based studies. In particular, C57BL/6 mice are frequently used in
      experiments into immunology and antitumor activity experiments. This study was
      compared the immunological characteristics of C57BL/6NKorl, a Korean developed
      experimental animal resource, with those of two other C57BL/6N substrains. Mouse
      body, thymus, and spleen weights in C57BL/6NKorl were not significantly different
      from those of the other two C57BL/6N substrains. Among the three substrains,
      there was no difference in the distribution of T and B cells, which are
      lymphocytes involved in adaptive immunity, and no difference in NK cells related
      to innate immunity. Results for macrophages and granulocytes, which have roles in
      innate immunity, were similar in all three substrains. In order to investigate
      the expressions of major histocompatibility complex (MHC) molecules and allogenic
      antigens, splenocytes were separated from obtained spleen and analyzed by using
      flow cytometry. MHC class I and II molecules, which are important during self/non
      self-discrimination, were similar in the three substrains. In addition,
      expression of alloantigen involved in allografts showed similar results in the
      three substrain. Thus, the results of this study provide strong evidence that
      C57BL/6NKorl is immunologically similar to two other C57BL/6N substrains.

PMID- 28747977
TI  - Use of C57BL/6N mice on the variety of immunological researches.
AB  - Inbred mice are an essential animal strain for research as they can improve the
      reproducibility and reliability of study results. The establishment of new inbred
      lines is continuing, and new inbred lines are being used in many research fields.
      C57BL/6 is a mouse laboratory animal that has been developed and used as an
      inbred strain since early stage of mouse strain development, and, in the 1950s,
      C57BL/6 was separated into substrains by the Jackson Laboratory (C57BL/6J) and
      the National Institutes of Health (C57BL/6N). C57BL/6 mice have been used in
      immunology and antitumor activity studies since the early strain development
      stage. After the mouse genome was fully described, C57BL/6 mice use in many areas
      of research has expanded. In particular, immunological characteristics such as
      those related to cell-mediated immunity and NK cell activity are relatively
      higher in C57BL/6 mice than in other mice. The C57BL/6NKorl is a stock of
      C57BL/6N established as part of a localization of experimental animal strategy of
      the Korean Food and Drug Administration. Based on analysis of single nucleotide
      polymorphisms (SNPs), C57BL/6NKorl is considered a genetically distinct inbred
      stock from other C57BL/6N. Various research efforts have been made to describe
      the characteristics and increase knowledge of the characteristics of
      C57BL/6Nkorl. The results obtained through these efforts are expected to increase
      the utilization of C57BL/6Nkorl as a domestic laboratory animal resource and to
      enhance the reliability of mouse based studies.

PMID- 28747979
TI  - Comparison of humoral and cell-mediated immunity in three different C57BL/6N
      mouse substrains.
AB  - Adaptive immunity is a type of immune response mediated by T and B cells, and is
      important response for immune response amplification and memory. In this study,
      the adaptive immunologic properties of C57BL/6NKorl substrain were compared with
      those of two other C57BL/6N substrains. There were no significant differences
      between the C57BL/6NKorl and the two other C57BL/6N substrains in the
      histological structures of the thymus and spleen, which are immunologic organs
      containing T cell and B cells. In addition, flow cytometric analysis did not
      reveal any significant differences in the distribution of T and B cell
      populations of the three substrains. To evaluate cell-mediated immunity of T
      cells in the three different substrains, we treated isolated T cells from spleen
      with Con A. The T cells of C57BL/6NKorl showed Con A-dependent proliferation of T
      cells at lower cell number than those in T cells from the other two C57BL/6N
      substrains. B cell-mediated humoral immune responses were not significant
      different among the three substrains. Thus, the results of this study provide
      evidence that C57BL/6NKorl mice are similar to those two other C57BL/6N
      substrains in humoral immunity, but C57BL/6NKorl has stronger response in cell
      mediated immunity.

PMID- 28747980
TI  - Comparative analysis of basal locomotor activity-related metabolic phenotypes
      between C57BL/6 mice and ICR mice substrains derived from three different
      sources.
AB  - Animal model, as an indispensable tool for scientific purposes of biomedical
      researches and clinical application, is a commonly used in various researches.
      Regarding to this, it is necessary to establish the metabolic phenotype of animal
      model to minimize spurious interpretations and ensure a level of accuracy and
      reliability adequate for experimental research. However, the metabolic phenotype
      related analysis within rodent strains derived from different source is
      nonexistent, especially in C57BL/6Korl mice and Korl:ICR mice (a domestic mouse
      strain). To compare the physiological and metabolic phenotypes over a period of
      time, we utilized the C57BL/6 mice (C57BL/6Korl, A:C57BL/6, and B:C57BL/6) and
      ICR mice (Korl:ICR, A:ICR, and B:ICR) derived from three different sources. Our
      data showed that average body weight, body temperature, food intake, and water
      consumption have a similar tendency among the C57BL/6 and ICR groups, except for
      the higher body weight of C57BL/6Korl mice over a period of time. Moreover, some
      significant differences was observed in adipose tissue mass and adipocyte size
      among the groups, with a higher tendency of C57BL/6Korl mice and Korl:ICR mice.
      Most importantly, resting metabolic rate (RMR) serves as an approximation of the
      metabolic phenotype showed no significant difference among the groups of C57BL/6
      mice and ICR mice, except for the lower oxygen uptake of C57BL/6Korl mice compare
      to the A:C57BL/6 mice. Taken together, our data suggest that C57BL/6 mice and ICR
      mice derived from three different sources have an overall similar feature of
      physiological and metabolic phenotypes.

PMID- 28747981
TI  - Comparison of the response using ICR mice derived from three different sources to
      multiple low-dose streptozotocin-induced diabetes mellitus.
AB  - This study was conducted to compare the multiple low-dose streptozotocin (MLDS)
      induced diabetic patterns of Korl:ICR, A:ICR, and B:ICR mice obtained from three
      different sources. Six-week-old male ICR mice were obtained from three difference
      sources. Korl:ICR mice were kindly provided by the National Institute of Food and
      Drug Safety Evaluation (NIFDS). The other two groups of ICR mice were purchased
      from different vendors located in the United States (A:ICR) and Japan (B:ICR).
      All ICR mice that received MLDS exhibited overt diabetic symptoms throughout the
      study, and the incidence and development of diabetes mellitus were similar among
      the three ICR groups. The diabetic mice exhibited hyperglycemia, loss of body
      weight gain, decreased plasma insulin levels, impaired glucose tolerance,
      decreased number of insulin-positive cells, and decreased size of beta-cells in
      the pancreas. The diabetes symptoms increased as the blood glucose level
      increased in the three ICR groups. In particular, the level of blood glucose in
      the STZ-treated group was higher in Korl:ICR and A:ICR mice than in B:ICR mice.
      The plasma insulin levels, glucose tolerance, blood chemistry, and morphological
      appearance of the pancreas were very similar in the ICR groups obtained from the
      three different sources. In conclusion, our results suggest that Korl:ICR, A:ICR,
      and B:ICR mice from different sources had similar overall responses to multiple
      low-dose STZ to induce diabetes mellitus.

PMID- 28747982
TI  - Comparative study of fatty liver induced by methionine and choline-deficiency in
      C57BL/6N mice originating from three different sources.
AB  - Non-alcoholic fatty liver disease (NAFLD) is believed to be the most prevalent
      liver disease worldwide and a major cause of chronic liver injury. It is
      characterized by lipid accumulation in the absence of significant alcohol
      consumption and frequently progresses to steatohepatitis, liver fibrosis, and
      hepatocellular carcinoma. Although many studies have been conducted to better
      understand NAFLD since it was first recognized, there are still many gaps in
      knowledge of etiology, prognosis, prevention and treatment. Methionine-choline
      deficient (MCD) diet, a well-established experimental model of NAFLD in rodents,
      rapidly and efficiently produces the clinical pathologies including
      macrovesicular steatosis and leads to disease progression. In this study, we
      measured the response to MCD diet in C57BL/6N mice obtained from three different
      sources; Korea NIFDS, USA, and Japan. We evaluated changes in body weight, food
      consumption, and relative weights of tissues such as liver, kidney, gonadal white
      adipose tissue, inguinal white adipose tissue, and brown adipose tissue. These
      basic parameters of mice with an MCD diet were not significantly different among
      the sources of mice tested. After 3 weeks on an MCD diet, histopathological
      analyses showed that the MCD diet induced clear fat vacuoles involving most area
      of the acinus in the liver of all mice. It was accompanied by increased serum
      activities of alanine aminotransferase and aspartate aminotransferase, and
      decreased levels of serum triglyceride and cholesterol. In conclusion, the
      response of C57BL6N mice originating from different sources to the MCD diet
      showed no significant differences as measured by physiological, biochemical, and
      histopathological parameters.

PMID- 28747983
TI  - Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different
      sources.
AB  - Doxorubicin is a widely used chemotherapeutic agents and is now part of standard
      therapeutic regimens for a variety of cancers (eg, hematopoietic malignancies and
      advanced solid tumors of the breast, ovary, thyroid, and bone). However, a
      potentially lethal and dose-dependent cardiotoxicity that appears within a short
      time after treatment limits the usage of doxorubicin in cancer patients. Although
      the mechanism of doxorubicin-induced cardiotoxicity is not completely understood,
      it is thought that free radical-induced oxidative stress and excessive production
      of reactive oxygen species are primary drivers of its toxicity. In this study, we
      compared the doxorubicin-induced cardiotoxicity of ICR mice obtained from three
      different sources and evaluated the utility of Korl:ICR stock established by the
      Korean FDA. Because doxorubicin-induced cardiotoxicity is thought to involve the
      excessive generation of ROS followed by oxidative stress, we determined the
      representative tissue index of oxidation, lipid peroxidation, and antioxidant,
      glutathione (GSH), as well as the parameters of heart injury. Doxorubicin
      treatment successfully induced cardiotoxicity as evidenced by histological
      examination and serum parameters (eg, levels of LDH and CK activities) in ICR
      mice. It was accompanied by increased lipid peroxidation and a decrease in both
      cysteine and GSH, further supporting previous reports that oxidative stress is a
      potential mechanism of doxorubicin-induced cardiotoxicity. Of interest, we did
      not observe a significant difference in doxorubicin-induced cardiotoxicity among
      mice of different origins. Collectively, our results suggest that Korl:ICR strain
      may be useful in the research of doxorubicin-induced cardiotoxicity.

PMID- 28747984
TI  - Annual tendency of research papers used ICR mice as experimental animals in
      biomedical research fields.
AB  - Institute of Cancer Research (ICR) mice have been widely used in various research
      fields including toxicology, oncology, pharmacology, and pharmaceutical product
      safety testing for decades. However, annual tendency of research papers involving
      ICR mice in various biomedical fields has not been previously analyzed. In this
      study, we examined the numbers of papers that used ICR mice as experimental
      animals in the social science, natural science, engineering, medicine-pharmacy,
      marine agriculture-fishery, and art-kinesiology fields by analyzing big data.
      Numbers of ICR mouse-used papers gradually increased from 1961 to 2014, but small
      decreases were observed in 2015 and 2016. The largest number of ICR-used papers
      were published in the medicine-pharmacy field, followed by natural science and
      art-kinesiology fields. There were no ICR mouse-used papers in other fields.
      Furthermore, ICR mice have been widely employed in cell biology studies within
      the natural science field as well as in biochemistry and pathology in the
      medicine-pharmacy field. Few ICR mouse-used papers were published in exercise
      biochemistry and exercise nutrition in the art-kinesiology field. Regardless in
      most fields, the total numbers of published papers involving ICR mice were higher
      in 2014 than in other years, although the numbers in some fields including
      dentistry, veterinary science, and dermatology were high in 2016. Taken together,
      the present study shows that various ICR stocks, including Korl:ICR mice, are
      widely employed as experimental animals in various biomedical research fields.

PMID- 28747985
TI  - Comparative study of fertilization rates of C57BL/6NKorl and C57BL/6N mice
      obtained from two other sources.
AB  - C57BL/6N is the most widely used inbred mouse strain applied in a wide variety of
      research areas including cancer, cardiovascular biology, developmental biology,
      diabetes and obesity, genetics, immunology, neurobiology, and sensorineural
      research. To compare the fertilization rates of C57BL/6NKorl mice with two
      commercial C57BL/6N stocks, differences in reproductive organ structures, sperm
      and egg numbers, fertilization rates, and embryo development rates among
      C57BL/6NKorl (Korea FDA source), C57BL/6NA (USA source), and C57BL/6NB (Japan
      source) mice were determined. Among the stocks, no significant differences were
      detected in organ weight and histological structure of male and female
      reproductive organs, although body weight was higher in C57BL/6NKorl mice than
      that in the other groups. The concentration and morphology of sperm and eggs in
      C57BL/6NKorl mice were similar to those of C57BL/6NA and C57BL/6NB mice.
      Furthermore, the three stocks had similar in vitro fertilization and embryo
      development rates, although these rates tended to be higher in C57BL/6NB mice.
      Pup body weight was higher in C57BL/6NKorl and C57BL/6NB mice than that in
      C57BL/6NA mice. The results of the present study suggest that C57BL/6NKorl,
      C57BL/6NA, and C57BL/6NB mice obtained from three different sources have similar
      fertilization and embryo development rates, although there were slight
      differences in the magnitude of their responses rates.

PMID- 28747986
TI  - Comparison of therapeutic responses to an anticancer drug in three stocks of ICR
      mice derived from three different sources.
AB  - Korl:ICR mice, established by the Korean National Institute of Food and Drug
      Safety Evaluation (NIFDS), are characterized based on their genetic variation,
      response to gastric injury, and response to constipation inducers. To compare the
      inhibitory responses of ICR stocks obtained from three different sources to the
      anticancer drug cisplatin (Cis), alterations in tumor volume, histopathological
      structure, and toxicity were examined in Sarcoma 180 tumor-bearing Korl:ICR,
      A:ICR (USA source), and B:ICR (Japan source) mice treated with low and high
      concentrations of Cis (L-Cis and H-Cis, respectively). Tumor size and volume were
      lower in H-Cis-treated mice than in L-Cis-treated mice in all three ICR stocks
      with no significant differences among stocks. There was a significant enhancement
      of the necrotizing areas in the histological structures in the L-Cis- and H-Cis
      treated groups relative to that in the untreated group. The necrotizing area
      changes were similar in the Sarcoma 180 tumor-bearing Korl:ICR, A:ICR, and B:ICR
      mice. However, there were stock-bases differences in the serum biomarkers for
      liver and kidney toxic effects. In particular, the levels of AST, ALT and BUN
      increased differently in the three H-Cis-treated ICR stocks, whereas the levels
      of ALP and CRE were constant. Taken together, the results of the present study
      indicate that Korl:ICR, A:ICR, and B:ICR mice have similar overall inhibitory
      responses following Cis treatment of Sarcoma 180-derived solid tumors, although
      there were some differences in the magnitude of the toxic effects in the three
      ICR stocks.

PMID- 28747987
TI  - Experimental determination of three-dimensional cervical joint mobility in the
      avian neck.
AB  - BACKGROUND: Birds have highly mobile necks, but neither the details of how they
      realize complex poses nor the evolution of this complex musculoskeletal system is
      well-understood. Most previous work on avian neck function has focused on
      dorsoventral flexion, with few studies quantifying lateroflexion or axial
      rotation. Such data are critical for understanding joint function, as
      musculoskeletal movements incorporate motion around multiple degrees of freedom
      simultaneously. Here we use biplanar X-rays on wild turkeys to quantify three
      dimensional cervical joint range of motion in an avian neck to determine patterns
      of mobility along the cranial-caudal axis. RESULTS: Range of motion can be
      generalized to a three-region model: cranial joints are ventroflexed with high
      axial and lateral mobility, caudal joints are dorsiflexed with little axial
      rotation but high lateroflexion, and middle joints show varying amounts axial
      rotation and a low degree of lateroflexion. Nonetheless, variation within and
      between regions is high. To attain complex poses, substantial axial rotation can
      occur at joints caudal to the atlas/axis complex and zygapophyseal joints can
      reduce their overlap almost to osteological disarticulation. Degrees of freedom
      interact at cervical joints; maximum lateroflexion occurs at different
      dorsoventral flexion angles at different joints, and axial rotation and
      lateroflexion are strongly coupled. Further, patterns of joint mobility are
      strongly predicted by cervical morphology. CONCLUSION: Birds attain complex neck
      poses through a combination of mobile intervertebral joints, coupled rotations,
      and highly flexible zygapophyseal joints. Cranial-caudal patterns of joint
      mobility are tightly linked to cervical morphology, such that function can be
      predicted by form. The technique employed here provides a repeatable protocol for
      studying neck function in a broad array of taxa that will be directly comparable.
      It also serves as a foundation for future work on the evolution of neck mobility
      along the line from non-avian theropod dinosaurs to birds.

PMID- 28747988
TI  - No speed dating please! Patterns of social preference in male and female house
      mice.
AB  - BACKGROUND: In many animal species, interactions between individuals of different
      sex often occur in the context of courtship and mating. During these
      interactions, a specific mating partner can be chosen. By discriminating
      potential mates according to specific characteristics, individuals can increase
      their evolutionary fitness in terms of reproduction and offspring survival. In
      this study, we monitored the partner preference behaviour of female and male wild
      house mice (Mus musculus domesticus) from populations in Germany (G) and France
      (F) in a controlled cage setup for 5 days and six nights. We analysed the effects
      of individual factors (e.g. population origin and sex) on the strength of
      preference (selectivity), as well as dyadic factors (e.g. neutral genetic
      distance and major histocompatibility complex (MHC) dissimilarity) that direct
      partner preferences. RESULTS: Selectivity was stronger in mice with a pure
      population background than mixed individuals. Furthermore, female mice with a
      father from the German population had stronger selectivity than other mice. In
      this group, we found a preference for partners with a larger dissimilarity of
      their father's and their partner's MHC, as assessed by sequencing the H2-Ebeta
      locus. In all mice, selectivity followed a clear temporal pattern: it was low in
      the beginning and reached its maximum only after a whole day in the experiment.
      After two days, mice seemed to have chosen their preferred partner, as this
      choice was stable for the remaining four days in the experiment. CONCLUSIONS: Our
      study supports earlier findings that mate choice behaviour in wild mice can be
      paternally influenced. In our study, preference seems to be potentially
      associated with paternal MHC distance. To explain this, we propose familial
      imprinting as the most probable process for information transfer from father to
      offspring during the offspring's early phase of life, which possibly influences
      its future partner preferences. Furthermore, our experiments show that
      preferences can change after the first day of encounter, which implies that
      extended observation times might be required to obtain results that allow a valid
      ecological interpretation.

PMID- 28747989
TI  - Biophysical interaction between corticosteroids and natural surfactant
      preparation: implications for pulmonary drug delivery using surfactant a a
      carrier.
AB  - Intratracheal administration of corticosteroids using a natural pulmonary
      surfactant as a delivery vehicle has recently received significant attention in
      hopes of treating premature newborns with or at high risk for chronic lung
      disease. As a new practice, both the surfactant preparation used as the carrier
      and the corticosteroid delivered as the anti-inflammatory agent, and their mixing
      ratios, have not been standardized and optimized. Given the concern that
      corticosteroids delivered via a pulmonary surfactant may compromise its surface
      activity and thus worsen lung mechanics, the present study was carried out to
      characterize the biophysical interaction between a natural surfactant
      preparation, Infasurf, and two commonly used inhaled corticosteroids, budesonide
      and beclomethasone dipropionate (BDP). Based on surface activity measurements by
      the Langmuir balance and lateral film structure studied by atomic force
      microscopy, our findings suggest that when Infasurf is used as a carrier, a
      budesonide concentration less than 1 wt% of surfactant or a BDP concentration up
      to 10 wt % should not significantly affect the biophysical properties of
      Infasurf, thus being feasible for pulmonary delivery. Increasing corticosteroid
      concentration beyond this range leads to early collapse of the surfactant film
      due to increased film fluidization. Our study further suggests that different
      affinities to the surfactant films are responsible for the different behavior of
      budesonide and BDP. In addition to the translational value in treating chronic
      lung disease, this study may also have implications in inhaled steroid therapy to
      treat asthma.

PMID- 28747990
TI  - Correlates of employment status in individuals with asthma: a cross-sectional
      survey.
AB  - BACKGROUND: This study aims to elucidate factors that among adults with asthma
      are associated with working full-time. METHODS: This cross-sectional survey of
      2613 working-age adults with asthma included questions on asthma history,
      symptoms and use of asthma medication, socioeconomic factors and health behavior.
      Full-time workers were compared to groups according to employment status:
      unemployed, work disability and retired due to age. RESULTS: Adults with asthma
      working full time were younger and more often nonmanual workers, experienced less
      asthma symptoms, used less asthma medication and smoked less than subjects with
      work disability. After adjusting for age, gender, smoking and professional
      status, having frequent symptoms of asthma during last month was associated with
      an increase in the risk of unemployment (OR 2.3, 95% CI 1.3-4.2) and with an
      increase in the risk of work disability (OR 4.4, 95% CI 2.3-8.2). CONCLUSIONS:
      Among adults with asthma, full-time work was associated with younger age, less
      symptomatic asthma despite of less medication, nonmanual work and less smoking.
      Having more severe symptoms of asthma was associated with undesirable employment
      status such as unemployment or work disability. Possibilities to change from
      manual to nonmanual work may be important in preventing work disability and early
      exit from work.

PMID- 28747991
TI  - A computational pipeline to generate MHC binding motifs.
AB  - BACKGROUND: Major histocompatibility complex (MHC) class I molecules play key
      roles in host immunity against pathogens by presenting peptide antigens to CD8+ T
      cells. Many variants of MHC molecules exist, and each has a unique preference for
      certain peptide ligands. Both experimental approaches and computational
      algorithms have been utilized to analyze these peptide MHC binding
      characteristics. Traditionally, MHC binding specificities have been described in
      terms of binding motifs. Such motifs classify certain peptide positions as
      primary and secondary anchors according to their impact on binding, and they list
      the preferred and deleterious residues at these positions. This provides a
      concise and easily communicatable summary of MHC binding specificities. However,
      so far there has been no algorithm to generate such binding motifs in an
      automated and uniform fashion. RESULTS: In this paper, we present a computational
      pipeline that takes peptide MHC binding data as input and produces a concise MHC
      binding motif. We tested our pipeline on a set of 18 MHC class I molecules and
      showed that the derived motifs are consistent with historic expert assignments.
      CONCLUSIONS: We have implemented a pipeline that formally codifies rules to
      generate MHC binding motifs. The pipeline has been incorporated into the immune
      epitope database and analysis resource (IEDB) and motifs can be visualized while
      browsing MHC alleles in the IEDB.

PMID- 28747992
TI  - Delta neutrophil index as an early predictor of acute appendicitis and acute
      complicated appendicitis in adults.
AB  - BACKGROUND: This retrospective study aimed to evaluate the ability of the delta
      neutrophil index (DNI) to predict histologically normal appendicitis
      preoperatively and to differentiate between simple and complicated appendicitis.
      METHODS: The data from 650 patients were divided into positive and negative
      appendectomy groups (histologically normal appendicitis). The patients in the
      acute appendicitis group were further sub-divided into simple and complicated
      appendicitis groups. RESULTS: The DNI was significantly higher in the positive
      group than in the negative appendectomy group (0.4 vs. -0.4, p < 0.001) as well
      as in the complicated group compared with that in the simple appendicitis group
      (1.2 vs. 0.3, p < 0.001). The DNI independently predicted a positive appendectomy
      and an acute complicated appendicitis in multivariate logistic regression
      analysis [odds ratio (OR) 2.62, 95% confidence interval (CI) (1.11~6.16), p =
      0.028 and odds ratio (OR) 4.10, 95% confidence interval (CI) (2.94~5.80), p <
      0.001]. The optimum cut-off for a positive appendectomy and acute complicated
      appendicitis were 0.2 [area under curve (AUC) 0.709] and 0.6 (AUC 0.727).
      CONCLUSIONS: We suggest that obtaining a preoperative DNI is a useful parameter
      to aid in the diagnosis of histologically normal appendicitis and to
      differentiate between simple and complicated appendicitis.

PMID- 28747993
TI  - Adolescent adaptive behavior profiles in Williams-Beuren syndrome, Down syndrome,
      and autism spectrum disorder.
AB  - BACKGROUND: Adaptive behavior can be impaired in different neurodevelopmental
      disorders and may be influenced by confounding factors, such as intelligence
      quotient (IQ) and socioeconomic classification. Our main objective was to verify
      whether adaptive behavior profiles differ in three conditions-Williams Beuren
      syndrome (WBS), Down syndrome (DS), and autism spectrum disorder (ASD), as
      compared with healthy controls (HC) and with each other. Although the literature
      points towards each disorder having a characteristic profile, no study has
      compared profiles to establish the specificity of each one. A secondary objective
      was to explore potential interactions between the conditions and socioeconomic
      status, and whether this had any effect on adaptive behavior profiles. METHODS:
      One hundred and five adolescents were included in the study. All adolescents
      underwent the following evaluations: the Vineland Adaptive Behavior Scale (VABS),
      the Wechsler Intelligence Scale for Children (WISC), and the Brazilian Economic
      Classification Criteria. RESULTS: Our results demonstrated that the WBS group
      performed better than the DS group in the communication domain, beta = -15.08,
      t(3.45), p = .005, and better than the ASD group in the socialization domain,
      beta = 8.92, t(-2.08), p = .013. The DS group also performed better than the ASD
      group in socialization, beta = 16.98, t(-2.32), p = .024. IQ was an important
      confounding factor, and socioeconomic status had an important effect on the
      adaptive behavior of all groups. CONCLUSIONS: There is a heterogeneity regarding
      adaptive behavior profiles in WBS, DS, and ASD. These data are important to
      better design specific strategies related to the health and social care of each
      particular group.

PMID- 28747994
TI  - Lignin valorization: lignin nanoparticles as high-value bio-additive for
      multifunctional nanocomposites.
AB  - BACKGROUND: Although conversion of low value but high-volume lignin by-product to
      its usable form is one of the determinant factors for building an economically
      feasible integrated lignocellulose biorefinery, it has been challenged by its
      structural complexity and inhomogeneity. We and others have shown that uniform
      lignin nanoparticles can be produced from a wide range of technical lignins,
      despite the varied lignocellulosic biomass and the pretreatment
      methods/conditions applied. This value-added nanostructure lignin enriched with
      multifunctional groups can be a promising versatile material platform for various
      downstream utilizations especially in the emerging nanocomposite fields. RESULTS:
      Inspired by the story of successful production and application of nanocellulose
      biopolymer, two types of uniform lignin nanoparticles (LNPs) were prepared
      through self-assembling of deep eutectic solvent (DES) and ethanol-organosolv
      extracted technical lignins derived from a two-stage fractionation pretreatment
      approach, respectively. Both LPNs exhibited sphere morphology with unique core
      shell nanostructure, where the DES-LNPs showed a more uniform particle size
      distribution. When incorporated into the traditional polymeric matrix such as
      poly(vinyl alcohol), these LPN products displayed great potential to formulate a
      transparent nanocomposite film with additional UV-shielding efficacy (reached
      ~80% at 400 nm with 4 wt% of LNPs) and antioxidant functionalities (reached ~160
      MUm mol Trolox g-1 with 4 wt% of LNPs). At the same time, the abundant phenolic
      hydroxyl groups on the shell of LNPs also provided good interfacial adhesion with
      PVA matrix through the formation of hydrogen bonding network, which further
      improved the mechanical and thermal performances of the fabricated LNPs/PVA
      nanocomposite films. CONCLUSIONS: Both LNPs are excellent candidates for
      producing multifunctional polymer nanocomposites using facile technical route.
      The prepared transparent and flexible LNPs/PVA composite films with high UV
      shielding efficacy, antioxidant activity, and biocompatibility are promising in
      the advanced packaging field, which potentially provides an additional high-value
      lignin product stream to the lignocellulose biorefinery. This study could open
      the door for the production and application of novel LNPs in the nascent
      bioeconomy.Graphical abstractLignin nanoparticle for transparent nanocomposite
      film with UV-shielding efficacy.

PMID- 28747995
TI  - Assessment of inhibitory effects on major human cytochrome P450 enzymes by
      spasmolytics used in the treatment of overactive bladder syndrome.
AB  - BACKGROUND: The objective of this study was to examine the inhibitory potential
      of darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine
      and trospium chloride on the seven major human cytochrome P450 enzymes (CYP) by
      using a standardized and validated seven-in-one cytochrome P450 cocktail
      inhibition assay. METHODS: An in vitro cocktail of seven highly selective probe
      substrates was incubated with human liver microsomes and varying concentrations
      of the seven test compounds. The major metabolites of the probe substrates were
      simultaneously analysed using a validated liquid chromatography tandem mass
      spectrometry (LC-MS/MS) method. Enzyme kinetics were estimated by determining
      IC50 and Ki values via nonlinear regression. Obtained Ki values were used for
      predictions of potential clinical impact of the inhibition using a static
      mechanistic prediction model. RESULTS: In this study, 49 IC50 experiments were
      conducted. In six cases, IC50 values lower than the calculated threshold for drug
      drug interactions (DDIs) in the gut wall were observed. In these cases, no
      increase in inhibition was determined after a 30 min preincubation. Considering a
      typical dosing regimen and applying the obtained Ki values of 0.72 uM
      (darifenacin, 15 mg daily) and 7.2 uM [propiverine, 30 mg daily, immediate
      release (IR)] for the inhibition of CYP2D6 yielded a predicted 1.9-fold and 1.4
      fold increase in the area under the curve (AUC) of debrisoquine (CYP2D6
      substrate), respectively. Due to the inhibition of the particular intestinal
      CYP3A4, the obtained Ki values of 14 uM of propiverine (30 mg daily, IR) resulted
      in a predicted doubling of the AUC for midazolam (CYP3A4 substrate). CONCLUSIONS:
      In vitro/in vivo extrapolation based on pharmacokinetic data and the conducted
      screening experiments yielded similar effects of darifenacin on CYP2D6 and
      propiverine on CYP3A4 as obtained in separately conducted in vivo DDI studies. As
      a novel finding, propiverine was identified to potentially inhibit CYP2D6 at
      clinically occurring concentrations.

PMID- 28747996
TI  - Triptorelin for the relief of lower urinary tract symptoms in men with advanced
      prostate cancer: results of a prospective, observational, grouped-analysis study.
AB  - BACKGROUND: Lower urinary tract symptoms (LUTSs) may develop in men with prostate
      cancer (PCa) and can impact quality of life (QoL). Gonadotropin-releasing hormone
      (GnRH) agonists as androgen deprivation therapy are standard treatment for PCa,
      however, data are limited on their effects on LUTSs. A grouped analysis of
      national observational, non-interventional studies initiated in clinical practice
      was performed to assess the effectiveness of triptorelin in reducing moderate or
      severe LUTSs, measured using the International Prostate Symptom Score (IPSS) in
      men with advanced or metastatic PCa. METHODS: Men with PCa and LUTSs scheduled to
      receive triptorelin (3-month or 1-month extended release formulation) were
      recruited into prospective, non-interventional studies at centres in Algeria,
      Australia, Belgium, China, Hungary, Romania and South Korea. The primary
      effectiveness endpoint was the proportion of patients with moderate or severe
      LUTSs, assessed by IPSS, after 48 weeks. Secondary endpoints included: total
      IPSS, QoL due to urinary symptoms (IPSS Question 8) and prostate-specific antigen
      (PSA) levels at 24 and 48 weeks. RESULTS: A total of 2701 patients were
      recruited; 1851 patients with moderate or severe LUTSs at baseline (IPSS > 7),
      received triptorelin and had follow-up IPSS (efficacy population). The proportion
      of patients with moderate or severe LUTSs was reduced to 67.2% from baseline at
      week 48, following a reduction to 75.9% at week 24: the overall time effect was
      significant (p < 0.001). QoL due to urinary symptoms significantly improved from
      a mean score of 3.7 at baseline, to adjusted means of 2.5 and 2.1, at weeks 24
      and 48, respectively (p < 0.001 versus baseline). Mean PSA levels were reduced
      from 158.8 ng/ml at baseline to 11.5 and 16.0 ng/ml at weeks 24 and 48,
      respectively. CONCLUSIONS: Within the limitations of these observational studies,
      improvements in LUTSs and QoL observed after 24 weeks and maintained at 48 weeks
      indicate that triptorelin-induced effects improve LUTSs in patients with advanced
      PCa.

PMID- 28747997
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/1756287217701665.].

PMID- 28748000
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.7448/IAS.20.01/21317.].

PMID- 28748001
TI  - A long-range interactive DNA methylation marker panel for the promoters of HOXA9
      and HOXA10 predicts survival in breast cancer patients.
AB  - BACKGROUND: Most DNA cancer methylation markers are based on the transcriptional
      regulation of the promoter-gene relationship. Recently, the importance of long
      range interactions between distal CpGs and target genes has been revealed. Here,
      we attempted to identify methylation markers for breast cancer that interact with
      distant genes. RESULTS: We performed integrated analysis using chromatin
      interactome data, methylome data, transcriptome data, and clinical information
      for breast cancer from public databases. Using the chromatin interactome and
      methylome data, we defined CpG-distant target gene relationships. After
      determining the differences in methylation between tumor and paired normal
      samples, the survival association, and the correlation between CpG methylation
      and distant target gene expression, we selected CpG methylation marker
      candidates. Using Cox proportional hazards models, we combined the selected
      markers and evaluated the prognostic model. We identified six methylation markers
      in HOXA9 and HOXA10 promoter regions and their long-range target genes. We
      experimentally validated the chromatin interactions, methylation status, and
      transcriptional regulation. A prognostic model showed that the combination of six
      methylation markers was highly associated with poor survival in independent
      datasets. According to our multivariate analysis, the prognostic model showed
      significantly better prognostic ability than other histological and molecular
      markers. CONCLUSIONS: The combination of long-range interacting HOXA9 and HOXA10
      promoter CpGs predicted the survival of breast cancer patients, providing a
      comprehensive and novel approach for discovering new methylation markers.

PMID- 28748002
TI  - High levels of circulating folate concentrations are associated with DNA
      methylation of tumor suppressor and repair genes p16, MLH1, and MGMT in elderly
      Chileans.
AB  - BACKGROUND: Changes in DNA methylation, one of the most studied epigenetic
      mechanisms, are considered an initial marker for early cancer detection. We
      evaluated how availability of dietary factors (folates and vitamin B12) involved
      in one-carbon metabolism may contribute to DNA methylation changes of cancer
      related genes in human subjects. METHODS: We studied, by pyrosequencing, the
      methylation of tumor suppressor gene p16, DNA repair genes MLH1 and MGMT, and the
      repetitive element LINE-1 (as a surrogate for global DNA methylation), in blood
      of elderly individuals (n = 249) who had been exposed to folic acid (FA) through
      FA-fortified wheat flour during the last 12 years. RESULTS: We found that serum
      folate and to a lesser extent, vitamin B12 concentrations, were significantly
      correlated with DNA methylation of p16, MLH1, and MGMT, but not with LINE-1. High
      serum folate concentrations (>45.3 nmol/L) were present in 31.1% of the
      participants. Although the methylated fraction of CpG sites in p16, MLH1, and
      MGMT was low (1.17-3.8%), high folate concentrations were significantly
      associated with methylation at the 3rd tertile of specific CpG sites in all genes
      with OR between 1.97 and 4.17. CONCLUSIONS: This study shows that a public
      policy, like food fortification with FA that increases circulating serum folate
      levels, could affect methylation levels of specific genes linked to cancer risk.
      Our present results deserve additional studies to clarify the real impact of high
      FA levels for risk of cancer in a whole population chronically exposed to a
      fortified food such as wheat flour. TRIAL REGISTRATION: ISRCTN 48153354 and
      ISRCTN 02694183.

PMID- 28748003
TI  - Patient attitudes towards community-based tuberculosis DOT and adherence to
      treatment in an urban setting; Kampala, Uganda.
AB  - INTRODUCTION: High Tuberculosis treatment default rate (17%) and sub-optimal
      treatment completion rates (45%) has burdened Kampala. Nevertheless, there are
      observable increase in the number of patients on TB DOT; from 6% to 29% in two
      consecutive annual reports. The main objective was to determine the association
      of TB patient attitudes towards community-based observers on the TB drug
      adherence on directly observed treatment for TB in Kampala. METHODS: A cross
      sectional study was carried out in Lubaga division, Kampala. A total of 201
      patients in continuation phase of treatment for Pulmonary TB (i.e. 8 to 20 weeks
      of TB treatment) were included in the study. Patient attitudes were measured
      using a 4-point Likert scale aggregated into a binary outcome with ''agree'' and
      ''disagree'' responses. Poisson regression model using a forward fitting approach
      in STATA v12 was used to determine the association between patient attitude
      towards CB-DOTs observers and adherence to TB treatment. RESULTS: Among the 201
      patients, 66% reported their treatment was being observed by someone. Relatives
      were the commonest (82%) treatment observers, 26% were non adherent to their TB
      treatment. Perceiving ''no need for a treatment observer'' and ''people rejecting
      TB patients'' were predictors of non-adherence to TB treatment (IRR=1.6,95%CI
      1.00-2.57;p=0.048) and (IRR=0.6, 95%CI 0.35-0.95; p=0.019) respectively.
      CONCLUSION: Patient's perceived attitude and stigma towards treatment observers
      contribute to non-adherence on TB treatment. For improved local TB control, more
      emphasis is needed to build a friendly environment between treatment supporters
      and patients during the course of TB treatment.

PMID- 28748004
TI  - [Dorsolumbar cold abscess revealing Pott's disease].
AB  - Tuberculous cold abscesses are a rare and unusual form of extrapulmonary
      tuberculosis. We here report the case of a 27-year old patient with a 5-month
      history of left dorsolumbar swelling presenting with dorsolumbar cold abscess
      revealing Pott's disease without neurological complications. Examination of pus
      sample collected at the time the abscess was incised and drained helped to
      confirm the diagnosis of cold abscesses of TB origin. The patient underwent 12
      months of anti-tuberculosis treatment which lead to a faster recovery; the
      sequelae was slight gibbosity.

PMID- 28748005
TI  - [Detection of complete common mesentery on CT scan for perforation in acute
      appendicitis].
AB  - Complete common mesentery is a rare abnormality in midgut rotation. Its detection
      is exceptional during adulthood because, during this period, is very often
      asymptomatic and therefore not diagnosed. Complete common mesentery may be
      discovered incidentally in patients with ectopic appendicular syndrome, as in our
      case study. We here report the case of a 42-year old patient presenting with
      acute clinico-biological pelvic inflammatory disorder. CT scan allowed the
      diagnosis of complete common mesentery associated with acute appendicitis.
      Laparotomy confirmed the diagnosis of perforated acute appendicitis associated
      with intestinal malrotation. Appendectomy outcomes were favorable.

PMID- 28748006
TI  - [Effectiveness of vaccine management and quality of immunization services in the
      Expanded Programme on Immunization (EPI) antenna in the Kisangani region,
      Democratic Republic of Congo].
AB  - INTRODUCTION: The quality of vaccines is critical for good immunization outcomes.
      It is dependent on the effectiveness of technical and logistics management system
      put in place. This study aimed to assess the effectiveness of vaccine management
      and to learn something from this. METHODS: We conducted a retrospective study of
      logistic management of vaccines in the Expanded Programme on Immunization (EPI)
      antenna in the Kisangani region over the period 2010-2014. A literature review
      completed by semi-structured interviews of immunization services managers and
      providers helped to evaluate vaccine management using the WHO GEV model in order
      to identify the gaps. RESULTS: Provider's demonstrated low level of knowledge of
      the vaccines that cannot be frozen, of freezing tests and of other vaccine
      damages. Computerized data management was properly ensured in the antenna. No
      evaluation criteria reached the goal of 80%. Compliance with the storage
      temperature was 70% in the antenna; the criterion for vaccine management was 65%
      and 67% in the health area central office and in the health centre respectively.
      The maintenance criterion was zero at all levels. CONCLUSION: Malfunctioning of
      the logistic system is remarkable at all levels of the health pyramid; this could
      interfere with the quality and the expected impact of vaccination. Particular
      attention should be paid to the maintenance of the equipment.

PMID- 28748007
TI  - Inguinal hernia surgery in developing countries: should laparoscopic repairs be
      performed ?

PMID- 28748008
TI  - [Precocious puberty in a little girl revealing malignant corticosurrenaloma].

PMID- 28748009
TI  - [Isolated double-chambered right ventricle (DCRV): a case study conducted at the
      National University Hospital CNHU-HKM in Cotonou, Benin].
AB  - Double-chambered right ventricle (DCRV) is a very rare cardiac defect in which
      the right ventricle is divided by anomalous muscle bundle into two chambers. It
      is associated with other malformations in 80-90% of cases. Clinical presentation
      varies and depends on the extent of the intraventricular obstruction. We here
      report the case of a 16-year old teenager with isolated DCRV revealed by
      recurrent syncopes. The diagnosis was made using Doppler echocardiography. The
      patient underwent successful surgical resection of the abnormal muscle band.

PMID- 28748010
TI  - [Acute acalculous gangrenous cholecystitis in postoperative period after
      orthopedic surgery: about a case].
AB  - Postoperative acalculous gangrenous cholecystitis is a serious and severe
      complication, especially in patients hospitalized in the Department of
      Reanimation. It occurs most often during vascular surgery or major digestive
      surgery, a polytrauma, in a context septic or in a context of shock. We report
      the case of a 74 year man who underwent surgery for femoral neck fracture. On the
      sixth postoperative day, he developed acute cholecystitis. Radiological
      examinations confirmed acalculous cholecystitis. After emergency cholecystectomy,
      anatomo-pathologic study confirmed the diagnosis of acalculous gangrenous
      cholecystitis.

PMID- 28748011
TI  - [Intraoperative management of esophageal atresia: small steps that cannot be
      ignored in Madagascar].
AB  - The management of esophageal atresia is still limited due to the precariousness
      of technical equipments in Madagascar. Our case study aims to highlight possible
      therapeutic options and to describe the progresses to be made so as to optimize
      treatment of this congenital pathology. We collected the medical records of all
      patients hospitalized for esophageal atresia in the Department of Surgical
      Reanimation at the University Hospital-JRA Antananarivo. The first patients
      admitted who survived for a period of 42 months (between January 2011 and June
      2014) were included in the study. Among the 17 patients admitted with esophageal
      atresia, three full-term newborns with type III esophageal atresia, successively
      admitted in Surgical Reanimation, were the first patients in Madagascar to
      survive after surgery. Only one patient had associated malformations. These three
      babies were extubated early in the operating room; they underwent oxygen therapy
      until normal spontaneous breathing. New-born babies underwent post-operatory
      physical therapy allowing to improve their respiratory status. Overall mortality
      rate from this pathology was 76.5% in 42 months. Despite these initial success,
      progresses still remain to be done in the treatment of this congenital anomaly,
      from diagnosis up to postoperative period. The improvement of technical
      equipments, especially ventilation and nutritional support equipments would allow
      more meaningful results, like in the countries where progresses has been made in
      the field of reanimation.

PMID- 28748012
TI  - [Association between Williams syndrome and adrenal insufficiency].
AB  - Williams syndrome is a developmental disorder including dysmorphia,
      cardiovascular malformations and a specific neuropsychological profile together
      with other associated disorders. We report the case of a 17-year old girl, born
      of a non-inbred marriage, with Williams syndrome discovered during an assessment
      of degree of failure to thrive. Its association with primary adrenal
      insufficiency makes it unique. Diagnosis is confirmed by cytogenetic and
      molecular analysis. Its management consists of the implementation of treatment
      for adrenal insufficiency associated with a clinico-biological monitoring.

PMID- 28748013
TI  - Chondroblastic osteosarcoma of the distal tibia: a rare case report.
AB  - Chondroblastic osteosarcoma, representing about 25% of osteosarcoma, is a fatal
      primary malignancy of the skeleton if not diagnosed and treated appropriately. It
      most commonly occurs in the long bones of the extremities near the metaphyseal
      growth plates. In this report, we describe the occurrence of chondroblastic
      osteosarcoma involving the left distal tibia in a 14-year-old male. The diagnosis
      was confirmed by the histological examination of a surgical biopsy. The patient
      was treated by both surgery and neoadjuvant chemotherapy. No recurrence was noted
      at 3 years of follow-up. To our knowledge, only two cases describing
      chondroblastic osteosarcoma of the distal tibia had been reported through English
      medical literature. Therefore, the aim of our article is to make the clinician
      aware of this rare clinical presentation and also to provide a comprehensive
      review of the literature related to this uncommon malignant tumour.

PMID- 28748014
TI  - [A typical shared psychotic disorder: about a case].
AB  - Shared psychotic disorder is a rare entity characterized by the transmission of
      delusional symptoms from one patient ("inducer") to another ("induced" partner).
      We here report a clinical observation of atypical shared psychotic disorder
      involving delusion of persecution and of grandeur in a teenager induced by two
      subjects (grand-father and paternal uncle) with two different types of
      psychiatric disorders, all of which present in the same subject (third-party).
      The nature of the content transmitted to the third subject was the sum of the
      ideas of the first two subjects. These three subjects had a close relationship
      and lived in a closed environment, without access to the outside world.

PMID- 28748015
TI  - Evaluation of problem-based learning curriculum implementation in a clerkship
      rotation of a newly established African medical training institution: lessons
      from the University of Botswana.
AB  - INTRODUCTION: Problem-based Learning (PBL) curricula, like all curricula, require
      systematic evaluation as there is a risk of implementing a dysfunctional PBL
      curriculum. The study intended to evaluate the PBL curriculum delivery from the
      perspective of the clerkship students at the University of Botswana-Faculty of
      Medicine. METHODS: A cross-sectional study was conducted among clerkship students
      in Family Medicine, Paediatrics, Internal Medicine and Surgery. During a 4-week
      period, each respondent completed weekly a questionnaire based survey tool. The
      three part questionnaire consisted of demographic data, 'seven-jumps' adapted
      from a 'typical' PBL tool to evaluate PBL process and 11 items 'adopted 'from the
      Short-Questionnaire-to-Evaluate-the-Effectiveness-of-Tutors in the PBL tool to
      evaluate the PBL facilitation with open ended questions at the end. RESULTS: Of
      the 81 eligible participants, 89% (n=72) responded. We collected back 141 (49%)
      forms out of the 288 expected (72 X 4 weeks). PBL first sessions took place all
      the time only in Family Medicine and in about 75% of the time in Pediatrics but
      none were conducted in the other disciplines. Overall, they evaluated the PBL
      process as 'good' (median= 8 /10) and the PBL facilitation as 'very good'
      (median=9 /10). Students appeared to have differing opinions on the preferred
      approach to the nature of patient problems that the PBL sessions should be
      structured around. CONCLUSION: Despite students rating PBL process as 'good' and
      facilitation as 'very good', PBL first sessions were not consistently undertaken.

PMID- 28748016
TI  - [Hepatic hematoma in neonates: about a case].
AB  - Hepatic hematoma is a condition of unrecognized origin which can become extremely
      serious and whose diagnosis is often made during perinatal autopsy. It is often
      characterised by nonspecific clinical manifestations and a long delay before
      biological presentation.The diagnosis is essentially based on ultrasound and
      treatment is often conservative.We here report a case of a full-term newborn with
      asymptomatic hepatic haematoma due to obstetrical trauma.

PMID- 28748017
TI  - [Factors associated with immunovirologic dissociation in HIV-1-infected patients
      under highly active antiretroviral therapy in the Ambulatory Treatment Center
      (ATC) in Dakar].
AB  - INTRODUCTION: The objective of this work is to evaluate the different factors
      associated with immunovirologic dissociation despite highly active and effective
      antiretroviral treatment. METHODS: We conducted a retrospective, cohort,
      descriptive and analytical study of the medical records of HIV-1 infected
      patients having received at least 12 months of antiretroviral therapy, followed
      in the ATC cohort from 2001 to 2011 and with undetectable viral load in the last
      6 months. RESULTS: During this 10-year study period, the prevalence of IVD was
      19.3%. Female sex was predominant, with a sex ratio of 1.9. Immunovirologic
      dissociation was more frequent in male patients (29.7% vs 14.1%) with a
      statistically significant difference (p = 0,00006). The average age was 44 years
      +/- 10 years. A history of tuberculosis was found in about a third of the cases
      (31.4%). Immunovirologic dissociation was significantly more frequent in patients
      with a history of tuberculosis (p = 0.00005). Most patients (68%) had AIDS at WHO
      clinical stages 3 or 4. Patients with immunovirologic dissociation were more
      often in WHO clinical stages 3 and 4 (p = 0.0001). More than half of the cases
      (56.2%) were found to be malnourished and immunovirologic dissociation was
      prevalent in malnourished patients (p=0.005). The mean CD4+ T lymphocytes counts
      was 86.7+/- 83 cells / mm3. Immunovirologic dissociation was more frequent in
      patients with initial low CD4+ T lymphocyte counts and with a statistically
      significant difference (p = 0.00000). By multivariate analysis, only age greater
      than or equal to 43 years, CD4 initial counts < 100 c/mm3 and male sex were
      significantly associated with this immunovirologic dissociation. CONCLUSION: Our
      study assessed the main factors associated with immunovirologic dissociation.
      Other studies of this nature would also merit consideration in order to highlight
      the impact of this partial immune response on the emergence of opportunistic
      infections or the implementation of a specific tritherapy for the sole purpose of
      producing fully successful immune restoration.

PMID- 28748018
TI  - [Abdominal mass revealing xanthogranulomatous pyelonephritis in an infant].
AB  - Xanthogranulomatous pyelonephritis (XGP) is a chronic pyelonephritis observed in
      children and exceptionally in infants. Symptomatology is vague and may delay
      diagnosis and patient's management. Treatment is based on medical therapy but
      most often on surgery with poor renal prognosis. We report the case of a 15-month
      old infant with isolated mass in the left flank. He had no fever or alteration of
      general state and urine cultures were sterile. Radiological evaluation (renal
      ultrasound, uroscan and renal scintigraphy) highlighted left non-functioning
      kidney with "hydropyonephrosis" evoking the diagnosis of XGP. The indication for
      total nephrectomy by lombotomy was posed and definitive anatomo-pathological
      examination confirmed the diagnosis of diffuse XGP. This observation emphasizes
      the importance of suspect PXG in patients with renal mass or malformative
      uropathy with recurrent urinary tract infections whose treatment should be
      rigorous and codified.

PMID- 28748019
TI  - [Desquamative erythrodermia].
AB  - Paraneoplastic dermatoses are a spectrum of cutaneous manifestations which may
      precede, coincide with or follow the diagnosis of cancer. Our study aims to
      remind clinicians that desquamative erythrodermia is a form of paraneoplastic
      dermatosis which may occur during hematologic malignancies. Hence the importance
      of a complete assessment to identify a neoplastic process in the presence of
      these clinical signs and especially when they are suspect.

PMID- 28748020
TI  - An unanticipated diagnosis with bedside ultrasonography in patients with acute
      abdominal pain: rectus hematoma.
AB  - Although abdominal pain is a common presentation in emergency departments, rectus
      sheath hematoma (RSH) is among the rarest diagnosis. Here we present 2 cases of
      RSH likely caused by coughing due to upper respiratory tract infection. The two
      described cases were diagnosed by bedside ultrasonography and confirmed as RSH by
      computed tomography. Review of patient history and use of ultrasonography are
      important to avoid misdiagnosisof RSH.

PMID- 28748021
TI  - An evaluation of the proposed organisation restructuring at Kadoma city, 2015.
AB  - INTRODUCTION: Restructuring is the corporate management term for the act of
      reorganizing the legal, operational, or other structures of a company for the
      purpose of making it more profitable or better organized for its present needs.
      However, preparing an organization to accept and welcome any change is crucial.
      There is concern though over poor service delivery, untimely payment of workers,
      top management structure which is thought to be top heavy and employee costs
      taking (58%) of total expenditure. METHODS: A descriptive cross sectional study
      was carried out. A cost benefit analysis was used to assess the cost and benefits
      of the proposed retrenchment exercise. A descriptive cross sectional study survey
      was conducted to assess the workers' perceptions towards the proposed
      restructuring exercise. A pretested self-administered questionnaire was used for
      data collection and data were analysed using EpiInfoTM (CDC 2012).Written
      informed consent was obtained from all study participants. RESULTS: Sixty nine
      percent of the respondents were males. The median years working for the
      organisation was 8 years (Q1=1; Q3=17). The total income was surpassed by
      expenditure with USD$11 000 and 52% of expenditures was going towards employment
      costs. A midyear financial review showed that 1% was channeled towards capital
      expenditure 2% on repairs and maintenance and employee costs accounting to 58% of
      all incurred expenditure. Current departmental salary budget amounted to USD
      3,3million dollars. Estimated salary costs for the proposed departmental
      structures amount to USD 3,8 million dollars. Comparison of the current and
      proposed structure showed that the proposed structure costs USD$486 000 more.
      Projected benefits of the proposed structure aims to improve service delivery
      from 60%-85% . Unlike managers, lower levels workers did not want the exercise to
      be carried out. CONCLUSION: The proposed structure has higher costs than the
      current structure but with more benefits in terms of service delivery. Generally
      workers perceived restructuring negatively and did not want it done.

PMID- 28748022
TI  - [Primary congenital lymphedema: Milroy disease: the first case observed in the
      Department of Pediatrics at the University Hospital Yalgado Ouedraogo,
      Ouagadougou].
AB  - Congenital lymphedema is the accumulation of lymphatic fluid in the child's
      interstitial spaces. Milroy disease is a rare, hereditary, autosomal dominant
      condition showing incomplete penetrance. We report the case of a 7-year old
      little girl with Milroy disease examined for erysipelas on congenital big right
      leg. A family history of large congenital member existed. Physical examination
      showed big oedematous right leg painful to palpation, with skin lichenification
      and erysipelas. Paraclinical assessment objectified cutaneous lymphedema with
      vascular involvement suggestive of ectasia of the right saphenous vein. Female
      karyotype showed no abnormalities, despite the small chromosomal rearrangements.
      Treatment was based on physiotherapy, bandages, compression stockings and
      psychotherapy. This first case in Burkina Faso testifies to the rarity of the
      pathology but especially to the diagnostic difficulties related to the inadequacy
      of paraclinical investigations.

PMID- 28748023
TI  - Antagonistic and Quantitative Assessment of Indigenous Lactic acid Bacteria in
      Different Varieties of Ogi against Gastrointestinal Pathogens.
AB  - INTRODUCTION: Ogi is a popular fermented cereal gruel consumed mainly in the
      western part of Nigeria. Traditionally, uncooked Ogi is normally administered to
      diarrhoea patients to reduce the frequency of stooling. This study was therefore
      undertaken to identify, quantify and determine the antimicrobial properties of
      lactic acid bacteria (LAB) isolated from Ogi. METHODS: The Ogi samples (Yellow,
      white, sorghum) were obtained from different market in Ibadan, Nigeria and Ogi
      control (cooked, uncooked and Omidun) were prepared with the viable counts of
      bacteria monitored over 5 days period. LAB were isolated from the varieties and
      identified by partial sequencing of 16S rRNA gene. The antimicrobial activities
      of the cell free supernatant (CFS) and the viable cells of the isolated LAB
      against Escherichia coli EC004, Salmonella sp. SS11, Shigella sp. SS10 were
      investigated by agar diffusion assay, agar overlay method, and coculture growth
      studies. RESULTS: Omidun had the highest LAB count while cooked ogi has the
      lowest LAB count. Weissella paramesenteroides , L. brevis, L. rossiae, L.
      fermentum, L. plantarum, Acetobacter pasteurianus, Paenibacillus sp. and Bacillus
      sp. were isolated from Ogi in this study. Large zone of inhibition (11<=x<=20)
      was observed with CFS against Salmonella sp. SS11 and Shigella sp. SS10 and also
      the overlay method. Coculture studies of Weissella paramesenteroides,
      Lactobacillus fermentum, and L. plantarum with Salmonella sp. SS11 showed a 5-8
      log reduction of the pathogens' growth after 24 hours as compared with the
      control. CONCLUSION: Ogi and its contents have antimicrobial properties against
      pathogenic organisms.

PMID- 28748024
TI  - Insights into Cedecea neteri strain M006 through complete genome sequence, a rare
      bacterium from aquatic environment.
AB  - Cedecea neteri M006 is a rare bacterium typically found as an environmental
      isolate from the tropical rainforest Sungai Tua waterfall (Gombak, Selangor,
      Malaysia). It is a Gram-reaction-negative, facultative anaerobic, bacillus. Here,
      we explore the features of Cedecea neteri M006, together with its genome sequence
      and annotation. The genome comprised 4,965,436 bp with 4447 protein-coding genes
      and 103 RNA genes.

PMID- 28748025
TI  - LARS NETWORK FILTRATION IN THE STUDY OF EEG BRAIN CONNECTIVITY.
AB  - In a brain network, weak and non-significant edge weights between nodes signal
      spurious connections and are often discarded by thresholding the weights.
      Traditional practice of thresholding edge weights at an arbitrary value can be
      problematic. Network filtration provides an alternative by summarizing the
      changes in the network topology with respect to a broad range of thresholds. A
      well established network filtration approach depends on the graphical-LASSO
      (least absolute shrinkage and selection operator) model, where a sequence of
      binary networks are obtained based on non-zero sparse inverse covariance (IC)
      estimates of partial correlations at a range of sparsity parameters. The
      limitation of the graphical-LASSO network model is that it relies on the
      structural information rather than actual entries of the sparse IC matrices and
      therefore can only yield approximate dynamic topological changes in the network.
      In the current study, we propose a new network filtration approach based on least
      angle regression (LARS) that gives exact filtration values at which the
      filtration changes and apply it to study brain connectivity in response to
      emotional stimuli across different age groups via electroencephalographic (EEG)
      data.

PMID- 28748026
TI  - TOPOLOGICAL EPILEPSY SEIZURE DETECTION IN ELECTROENCEPHALOGRAPHIC SIGNALS.
AB  - We propose a seizure detection method for electroencephalographic (EEG) epilepsy
      data based on a novel multi-scale topological technique called persistent
      homology (PH). Among several PH descriptors, persistence landscape (PL) possesses
      many desirable properties for rigorous statistical inference. By building PLs on
      EEG epilepsy signals smoothed by a weighted Fourier series (WFS) expansion, we
      compared the before and during phases of a seizure attack in a patient diagnosed
      with left temporal epilepsy and successfully identified site T3 as the origin of
      the seizure attack.

PMID- 28748027
TI  - Oral candidiasis among African human immunodeficiency virus-infected individuals:
      10 years of systematic review and meta-analysis from sub-Saharan Africa.
AB  - Oral candidiasis (OC) is the most common opportunistic fungal infection among
      immunocompromised individuals. This systematic review and meta-analysis reports
      on the contribution of non-albicans Candida species in causing OC among human
      immunodeficiency virus (HIV)-infected individuals in sub-Saharan Africa between
      2005 and 2015. Thirteen original research articles on oral Candida
      infection/colonization among HIV-infected African populations were reviewed. The
      prevalence of OC ranged from 7.6% to 75.3%. Pseudomembranous candidiasis was
      found to range from 12.1% to 66.7%. The prevalence of non-albicans Candida
      species causing OC was 33.5% [95% confidence interval (CI) 30.9-36.39%]. Of 458
      non-albicans Candida species detected, C. glabrata (23.8%; 109/458) was the most
      common, followed by C. tropicalis (22%; 101/458) and C. krusei (10.7%; 49/458).
      The overall fluconazole resistance was 39.3% (95% CI 34.4-44.1%). Candida
      albicans was significantly more resistant than non-albicans Candida species to
      fluconazole (44.7% vs 21.9%; p < 0.001). One-quarter of the cases of OC among HIV
      infected individuals in sub-Saharan Africa were due to non-albicans Candida
      species. Candida albicans isolates were more resistant than the non-albicans
      Candida species to fluconazole and voriconazole. Strengthening the capacity for
      fungal diagnosis and antifungal susceptibility testing in sub-Saharan Africa is
      mandatory in order to track the azole resistance trend.

PMID- 28748028
TI  - Porphyromonas gingivalis suppresses invasion of Fusobacterium nucleatum into
      gingival epithelial cells.
AB  - Invasion of periodontal pathogens into periodontal tissues is an important step
      that can cause tissue destruction in periodontal diseases. Porphyromonas
      gingivalis is a keystone pathogen and its gingipains are key virulence factors.
      Fusobacterium nucleatum is a bridge organism that mediates coadhesion of disease
      causing late colonizers such as P. gingivalis and early colonizers during the
      development of dental biofilms. The aim of this study was to investigate how P.
      gingivalis, in particular its gingipains, influences the invasion of coinfecting
      F. nucleatum into gingival epithelial cells. When invasion of F. nucleatum was
      analyzed after 4 h of infection, invasion of F. nucleatum was suppressed in the
      presence of P. gingivalis compared with during monoinfection. However,
      coinfection with a gingipain-null mutant of P. gingivalis did not affect invasion
      of F. nucleatum. Inhibition of PI3K reduced invasion of F. nucleatum. P.
      gingivalis inactivated the PI3K/AKT pathway, which was also dependent on
      gingipains. Survival of intracellular F. nucleatum was promoted by P. gingivalis
      with Arg gingipain mutation. The results suggest that P. gingivalis, in
      particular its gingipains, can affect the invasion of coinfecting F. nucleatum
      through modulating intracellular signaling of the host cells.

PMID- 28748029
TI  - Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus
      colonization among human immunodeficient virus-infected outpatients in Taiwan:
      oral Candida colonization as a comparator.
AB  - Human immuodeficency virus (HIV)-infected patients receiving highly active
      antiretroviral therapy (HAART) and community-associated methicillin-resistant
      Staphylococcus aureus (CA-MRSA) have increased in recent years in Taiwan. This
      study was undertaken to determine the prevalence of and risk factors for nasal
      and oral S. aureus and MRSA colonization among contemporary HIV-infected
      populations. Clinical variables for S. aureus and MRSA colonization among HIV
      infected outpatients from three hospitals were analyzed and compared with those
      for oral Candida colonization. Genetic characteristics of MRSA isolates were
      analyzed. A total of 714 patients were screened for nasal S. aureus colonization,
      and a subset of 457 patients were also screened for oral S. aureus colonization.
      Of all patients, 79.4% were receiving HAART, and their mean CD4 count was 472
      cells/mm3. The colonization rates in the oral cavity, nasal cavity, and at either
      site were 18.8%, 31.7%, and 36.8%, respectively, for S. aureus, and 3.1%, 4.4%,
      and 5.5%, respectively, for MRSA. These rates were all much lower than the
      previously reported rate of oral Candida colonization (52.4%). By multivariate
      analysis, a suppressed viral load (<200 copies/mL) protected against oral S.
      aureus, MRSA, and Candida colonization, and recent use of antibacterial agents
      protected against oral and nasal S. aureus colonization. Recent incarceration
      increased the risk of nasal MRSA colonization, while recent hospitalization,
      tuberculosis, older age, and intravenous drug use increased the risk of oral
      Candida colonization. Candida spp. did not augment S. aureus or MRSA colonization
      in the oral cavity. Most of the 41 MRSA isolates recovered belonged to the SCCmec
      IV/pvl-negative (51.2%) and VT/pvl-positive (26.8%) ST59 local prevalent CA-MRSA
      clones. Distinct carriage rates demonstrated here suggested that mucosal immunity
      against colonization might differ in terms of microbes and sites. A decreased
      risk in oral carriage of MRSA and Candida might be a benefit of HAART.

PMID- 28748030
TI  - 16S rDNA analysis of periodontal plaque in chronic obstructive pulmonary disease
      and periodontitis patients.
AB  - This study investigated if chronic obstructive pulmonary disease (COPD) is
      correlated with periodontitis via periodontal microbiota and if certain bacteria
      affect periodontitis as well as COPD. Moreover, the study investigated whether
      suffering from COPD is associated with a decrease in the richness and diversity
      of periodontal microbiota. Subgingival plaque was obtained from 105 patients.
      Bacterial DNA was isolated from 55 COPD and 50 non-COPD participants (either with
      or without periodontitis). 16S rRNA gene metagenomic sequencing was used to
      characterize the microbiota and to determine taxonomic classification. In the non
      periodontitis patients, suffering from COPD resulted in a decrease in bacteria
      richness and diversity in the periodontal microenvironment. An increase in the
      genera Dysgonomonas, Desulfobulbus, and Catonella and in four species
      (Porphyromonas endodontalis, Dysgonomonas wimpennyi, Catonella morbi, and
      Prevotella intermedia) in both COPD and periodontitis patients suggests that an
      increase in these periodontitis-associated microbiota may be related to COPD.
      Three genera (Johnsonella, Campylobacter, and Oribacterium) were associated with
      COPD but not with periodontitis. The decrease in the genera Arcanobacterium,
      Oribacterium, and Streptomyces in COPD patients implies that these genera may be
      health-associated genera, and the decrease in these genera may be related to
      disease. These data support the hypothesis that COPD is correlated with
      periodontitis via these significantly changed specific bacteria.

PMID- 28748031
TI  - Antibiofilm peptides against oral biofilms.
AB  - The oral cavity is a major entry point for bacteria and other microorganisms.
      Oral biofilms are formed by mixed communities of microorganisms embedded in an
      exopolysaccharide matrix. Biofilms forming on dental hard or soft tissue are the
      major cause of caries and endodontic and periodontal disease. Human oral biofilms
      exhibit high resistance to antimicrobial agents. Antibiofilm peptides constitute
      a diverse class of host-defense molecules that act to combat invasion and
      infection with biofilms. Different in vitro and in vivo biofilm models with
      quantitative analysis have been established to provide predictable platforms for
      the evaluation of the antibiofilm effect of oral antibiofilm peptides. These
      peptides have engendered considerable interest in the past decades as potential
      alternatives to traditional disinfecting agents due to their ability to target
      bacterial biofilms specifically, leading to the prevention of biofilm formation
      and destruction of pre-existing biofilms by Gram-positive and -negative bacterial
      pathogens and fungi. At the same time, challenges associated with the application
      of these antibiofilm peptides in dental practice also exist. The production of
      effective, nontoxic, and stable antibiofilm peptides is desired in both academic
      and industrial fields. This review focuses on the antibiofilm properties of
      current synthetic peptides and their application in different areas of dentistry.

PMID- 28748032
TI  - Biofilm sensitivity of seven Streptococcus mutans strains to different fluoride
      levels.
AB  - The effect of fluoride concentrations in dental products could be different
      depending on the Streptococcus mutans strain. The aim of this study was to
      investigate the effect of different fluoride concentrations corresponding to
      dental products on biofilm formation and metabolic activity of S. mutans strains.
      Seven S. mutans strains (UA159, A32-2, NG8, 10449, UA130, LM7, and OMZ175) were
      inoculated into 96-well microtiter plates and were tested with various
      concentrations of sodium fluoride (0.0, 1.0, 1.56, 3.13, 6.25, 12.5, 25, 50, 100,
      125, 175, 225, 275, 625, 1,250, 2,250, and 5,500 ppm) for inhibition of biofilm
      formation and bacterial metabolic activity by recording absorbance values
      followed by scanning electron microscope (SEM) images. Data were analyzed by one
      way analysis of variance and Tukey's tests (alpha = 5%). Significantly more
      (p<=0.05) biofilm mass in the presence of fluoride was produced by A32-2 and NG8.
      UA130, LM7, and OMZ175 were more sensitive to increased fluoride and demonstrated
      few bacterial cells and extracellular polysaccharide (EPS) production at 100 ppm
      in SEM images. All strains were unable to produce significant biofilm at
      concentrations >225 ppm. Patients with tolerantS. mutans strains would
      potentially benefit less from the inherent antibacterial effect of fluoride.

PMID- 28748033
TI  - Candida and Porphyromonas gingivalis: the effect on wound closure in vitro.
AB  - Microorganisms play a role in oral mucositis after cancer therapy. The current
      study explored the hypothesis that Candida spp. alone and together with
      Porphyromonas gingivalis cause delayed healing of oral ulcerations due to the
      inhibition of wound closure. An in vitro scratch assay model was used to study
      the influence of viable and heat-killed Candida glabrata, Candida kefyr, and
      Candida albicans on cell migration of oral epithelial cells. Separately, the
      effect of conditioned medium of Candida spp. and the effect of a mixed infection
      of Candida spp. with P. gingivalis on wound closure was studied. In the presence
      of 10 viable C. glabrata or C. kefyr versus one epithelial cell, with a
      multiplicity of infection (MOI) of 10, the relative closure of the scratch was
      26% and 17%, respectively. At a MOI of 1, this was 60% for C. glabrata and 78%
      for C. kefyr. The inhibition of oral epithelial cell migration challenged with
      either C. glabrata or C. kefyr together with P. gingivalis was stronger than the
      inhibition caused by one of both organisms separately. Candida spp. inhibit cell
      migration in vitro. A combination of Candida spp. and P. gingivalis inhibited
      cell migration more than either microorganism separately.

PMID- 28748034
TI  - Porphyromonas gingivalis may interfere with conception in women.
AB  - In this observational and prospective study, we investigated if microbiological
      and serological markers of periodontitis associated with conception in 256 non
      pregnant women (Mage = 29.2 years; range 19-42 years). Clinical oral and
      gynecological examinations were performed, major periodontal pathogens in the
      saliva were detected, and serum and saliva antibodies against major periodontal
      pathogens were analyzed. The follow-up period for becoming pregnant was 12
      months. Porphyromonas gingivalis was significantly (p = 0.032) more frequently
      detected in the saliva among those who did not become pregnant (8.3%) than among
      those who became pregnant (2.1%). The median levels of salivary P. gingivalis
      immunoglobulin A (IgA; p = 0.006) and IgG (p = 0.007) antibodies were higher
      among those who did not become pregnant compared to those who became pregnant.
      Hazard ratios (HR) for not becoming pregnant were HR = 3.75 (95% confidence
      interval [CI] 1.01-13.9; p = 0.048) if the subject was polymerase chain reaction
      positive for P. gingivalis with high salivary antibodies against it, and HR =
      1.62 (95% CI 1.03-2.54; p = 0.035) if she had high levels of serum P. gingivalis
      IgA and signs of periodontal infection. P. gingivalis associated with no success
      in getting pregnant.

PMID- 28748035
TI  - Cytokine response patterns to complex biofilms by mononuclear cells discriminate
      patient disease status and biofilm dysbiosis.
AB  - Localized aggressive periodontitis (LAP) is a rare form of periodontal disease
      with site-specific rapid tissue destruction. A lipopolysaccharide (LPS) hyper
      inflammatory response was shown in LAP using peripheral whole blood, although
      responses to other bacterial surface components or complex oral biofilms have not
      been evaluated. Peripheral blood mononuclear cells (PBMCs) from 14 LAP patients,
      15 healthy siblings (HS), and 13 unrelated healthy controls (HC) were stimulated
      with: LPS, lipoteichoic acid, or peptidoglycan; intact or sonically dispersed in
      vitro-grown biofilms from a LAP disease site, a LAP healthy site, or a healthy
      control site. Cell culture supernatants were assayed for 14 cyto/chemokines.
      Discriminant function analysis determined cyto/chemokines that discriminate
      disease status by response patterns to different stimuli. Qualitative differences
      in the cytokine response pattern among patient groups were observed to intact and
      dispersed biofilms, yet responses to healthy and diseased biofilms could not be
      discriminated. Despite an equivalent magnitude of response, LAP-derived PBMCs
      demonstrated a qualitatively different pattern of response to LPS and dispersed
      biofilms. PMBCs from each group responded distinctly to stimulation
      withsubgingival biofilms. Multiple underlying mechanisms related to bacterial
      induced inflammatory responses can culminate in LAP disease initiation and/or
      progression, and biofilm homeostasis could play an important role.

PMID- 28748037
TI  - Periodontitis, pathogenesis and progression: miRNA-mediated cellular responses to
      Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is considered a keystone pathogen in periodontitis, a
      disease typically driven by dysbiosis of oral inflammophilic polymicrobial
      pathobionts. To combat infectious agents, the natural defense response of the
      host is to switch on inflammatory signaling cascades, whereby microRNA (miRNA)
      species serve as alternative genetic inhibitory transcriptional endpoints. miRNA
      profiles from diseased sites differ from those detected in disease-free tissues.
      miRNA profiles could therefore be harnessed as potential diagnostic/prognostic
      tools. The regulatory role of some miRNA species (miRNA-128, miRNA-146, miRNA
      203, and miRNA-584) in the innate immune system suggests these molecular
      signatures also have potential in therapy. P. gingivalis-associated miRNAs are
      likely to influence the innate immune response, whereas its lipopolysaccharide
      may affect the nature of host miRNAs and their mRNA targets. This mini review
      discusses miRNA-dependent transcriptional and regulatory phenomena ensuing immune
      signaling cascade switch-on with development and progression of periodontitis
      initiated by P. gingivalis exposure.

PMID- 28748036
TI  - Comorbidity of periodontal disease: two sides of the same coin? An introduction
      for the clinician.
AB  - Increasing evidence has suggested an independent association between
      periodontitis and a range of comorbidities, for example cardiovascular disease,
      type 2 diabetes, rheumatoid arthritis, osteoporosis, Parkinson's disease,
      Alzheimer's disease, psoriasis, and respiratory infections. Shared inflammatory
      pathways are likely to contribute to this association, but distinct causal
      mechanisms remain to be defined. Some of these comorbid conditions may improve by
      periodontal treatment, and a bidirectional relationship may exist, where, for
      example, treatment of diabetes can improve periodontal status. The present
      article presents an overview of the evidence linking periodontitis with selected
      systemic diseases and calls for increased cooperation between dentists and
      medical doctors to provide optimal screening, treatment, and prevention of both
      periodontitis and its comorbidities.

PMID- 28748038
TI  - Porphyromonas gingivalis and its lipopolysaccharide differently modulate
      epidermal growth factor-dependent signaling in human gingival epithelial cells.
AB  - Periodontitis is an inflammatory disease induced by pathogenic bacteria such as
      Porphyromonas gingivalis. Little is known about epidermal growth factor (EGF)
      signals in human gingival epithelial cells (HGEC), which are major targets of P.
      gingivalis, and how the expression of proteins participating in EGF signaling
      that is, EGF-receptor (EGFR), suppressor of cytokine signaling-3 (SOCS-3),
      interferon regulatory factor-1 (IRF-1), and signal transducers and activators of
      transcription (STAT-3)-are modified. This study aimed to assess the effects of P.
      gingivalis and its purified lipopolysaccharide (LPS-Pg) on EGF signaling. HGEC
      were infected for 2 h in a dose-dependent manner with P. gingivalis and with heat
      killed P. gingivalis, and activated for 2 and 24 h by 1 ug/mL of purified LPS-Pg.
      Quantitative reverse transcription polymerase chain reaction and Western blotting
      were performed to measure mRNA and protein levels for SOCS-3, IRF-1 EGF, EGFR,
      and STAT-3. The tyrosine-phosphorylation status of STAT-3 was also examined. The
      results showed that infection of HGEC cells with P. gingivalis, but not with heat
      killed P. gingivalis, led to significant reductions in expression levels of mRNAs
      and proteins for SOCS-3, IRF-1, and EGFR, while LPS-Pg over time significantly
      increased the expression of these mRNAs and proteins. Tyrosine-phosphorylation of
      STAT-3 was significantly increased during infection with P. gingivalis and
      activation by LPS-Pg but not modified during infection with heat-killed P.
      gingivalis. This study highlights that P. gingivalis and its purified LPS
      differentially modulated the expression of proteins (SOCS-3, IRF-1, EGFR, and
      STAT-3) interfering with EGF signaling.

PMID- 28748039
TI  - Age-related prevalence and characteristics of Aggregatibacter
      actinomycetemcomitans in periodontitis patients living in Sweden.
AB  - Background: The presence of Aggregatibacter actinomycetemcomitans in patients
      with periodontitis has been extensively studied for decades. Objective: To study
      the prevalence of A. actinomycetemcomitans in younger and older periodontitis
      patients and to genetically characterize isolates of this bacterium. Design: Data
      from microbiological analyses of 3459 subgingival plaque samples collected from
      1445 patients, 337 'younger' patients (<=35 yrs) and 1108 'older' patients (>35
      yrs) during 15 years (2000-2014), has been summerized. Isolates of A.
      actinomycetemcomitans were serotyped, leukotoxin promoter typed (JP2 and non JP2)
      and arbitrarily primed PCR (AP-PCR) genotyped. The origin of the JP2 genotype
      detected in the study population was determined. Results: The prevalence of A.
      actinomycetemcomitans was higher among younger than older patients and samples
      from the younger patients contained higher proportions of the bacterium. Serotype
      b was more prevalent among younger patients and the majorty of these isolates was
      from the same AP-PCR genotype. The JP2 genotype was detected in 1.2% of the
      patients, and the majority of these carriers were of non-African origin.
      Conslusions: For presence and charcteristics of A. actinomycetemcomitans in
      clinical samples the age of the carriers were a discriminating factor.
      Additional, apparently non-African carriers of the JP2 genotype of A.
      actinomycetemcomitans were identified.

PMID- 28748040
TI  - Effect of erythritol on microbial ecology of in vitro gingivitis biofilms.
AB  - Gingivitis is one of the most common oral infections in humans. While sugar
      alcohols such as erythritol are suggested to have caries-preventive properties,
      it may also have beneficial effects in prevention of gingivitis by preventing
      maturation of oral biofilms. The aim of this study was to assess the effect of
      erythritol on the microbial ecology and the gingivitis phenotype of oral
      microcosms. Biofilms were inoculated with stimulated saliva from 20 healthy
      donors and grown in a gingivitis model in the continuous presence of 0 (control
      group), 5, and 10% erythritol. After 9 days of growth, biofilm formation,
      protease activity (gingivitis phenotype), and microbial profile analyses were
      performed. Biofilm growth was significantly reduced in the presence of
      erythritol, and this effect was dose dependent. Protease activity and the Shannon
      diversity index of the microbial profiles of the biofilms were significantly
      lower when erythritol was present. Microbial profile analysis revealed that
      presence of erythritol induced a compositional shift from periodontitis- and
      gingivitis-related taxa toward early colonizers. The results of this study
      suggest that erythritol suppresses maturation of the biofilms toward unhealthy
      composition. The gingivitis phenotype was suppressed and biofilm formation was
      reduced in the presence of erythritol. Therefore, it is concluded that erythritol
      may contribute to a healthy oral ecosystem in vitro.

PMID- 28748041
TI  - Effect of azithromycin on a red complex polymicrobial biofilm.
AB  - Azithromycin has recently gained popularity for the treatment of periodontal
      disease, despite sparse literature supporting efficiency in treating periodontal
      bacterial biofilms. The aim of this study was to evaluate the effect of
      azithromycin on biofilms comprised of Porphyromonas gingivalis, Treponema
      denticola, and Tannerella forsythia in comparison to an amoxicillin and
      metronidazole combination. P. gingivalis W50, T. denticola ATCC35405, and T.
      forsythia ATCC43037 grown under anaerobic conditions at 37 degrees C were
      aliquoted into 96-well flat-bottom plates in different combinations with addition
      of azithromycin or amoxicillin + metronidazole at various concentrations. For the
      biofilm assay, the plates were incubated at 37 degrees C anaerobically for 48 h,
      after which the biofilms were stained with crystal violet and measured for
      absorbance at AU620. In this model, polymicrobial biofilms of P. gingivalis + T.
      denticola, P. gingivalis + T. forsythia, and T. denticola + T. forsythia were
      cultured. Combination of all three bacteria enhanced biofilm biomass.
      Azithromycin demonstrated a minimal biofilm inhibitory concentration (MBIC) of
      10.6 mg/L, while the amoxicillin + metronidazole combination was more effective
      in inhibiting biofilm formation with a MBIC of 1.63 mg/L. Polymicrobial biofilm
      formation was demonstrated by combination of all three red complex bacteria.
      Azithromycin was ineffective in preventing biofilm formation within a clinically
      achievable concentration, whereas the combination of amoxicillin and
      metronidazole was more effective for this purpose.

PMID- 28748042
TI  - Porphyromonas gingivalis disturbs host-commensal homeostasis by changing
      complement function.
AB  - Porphyromonas gingivalis is a Gram-negative anaerobic rod that has been proposed
      as an orchestrator of complement-dependent dysbiotic inflammation. This notion
      was suggested from its capacities to manipulate the complement-Toll-like receptor
      crosstalk in ways that promote dysbiosis and periodontal disease in animal
      models. Specifically, while at low colonization levels, P. gingivalis interferes
      with innate immunity and leads to changes in the counts and composition of the
      oral commensal microbiota. The resulting dysbiotic microbial community causes
      disruption of host-microbial homeostasis, leading to inflammatory bone loss.
      These findings suggested that P. gingivalis can be considered as a keystone
      pathogen. The concept of keystone pathogens is one where their effects have
      community-wide significance and are disproportionate of their abundance. The
      present review summarizes the relevant literature and discusses whether the
      results from the animal models can be extrapolated to man.

PMID- 28748043
TI  - Fluoride resistance in Streptococcus mutans: a mini review.
AB  - For decades, fluoride has been used extensively as an anti-caries agent. It not
      only protects dental hard tissue, but also inhibits bacterial growth and
      metabolism. The antimicrobial action of fluoride is shown in three main aspects:
      the acidogenicity, acidurance, and adherence to the tooth surface. To counteract
      the toxic effect of fluoride, oral bacteria are able to develop resistance to
      fluoride through either phenotypic adaptation or genotypic changes. Strains that
      acquire fluoride resistance through the latter route show stable resistance and
      can usually resist much higher fluoride levels than the corresponding wild-type
      strain. This review summarizes the characteristics of fluoride-resistant strains
      and explores the mechanisms of fluoride resistance, in particular the recent
      discovery of the fluoride exporters. Since the fluoride resistance of the
      cariogenic bacterium Streptococcus mutans has been studied most extensively, this
      review mainly discusses the findings related to this species.

PMID- 28748044
TI  - Visualizing the dental biofilm matrix by means of fluorescence lectin-binding
      analysis.
AB  - The extracellular matrix is a poorly studied, yet important component of dental
      biofilms. Fluorescence lectin-binding analysis (FLBA) is a powerful tool to
      characterize glycoconjugates in the biofilm matrix. This study aimed to
      systematically investigate the ability of 75 fluorescently labeled lectins to
      visualize and quantify extracellular glycoconjugates in dental biofilms. Lectin
      binding was screened on pooled supragingival biofilm samples collected from 76
      subjects using confocal microscopy. FLBA was then performed with 10 selected
      lectins on biofilms grown in situ for 48 h in the absence of sucrose. For five
      lectins that proved particularly suitable, stained biovolumes were quantified and
      correlated to the bacterial composition of the biofilms. Additionally,
      combinations of up to three differently labeled lectins were tested. Of the 10
      lectins, five bound particularly well in 48-h-biofilms: Aleuria aurantia (AAL),
      Calystega sepiem (Calsepa), Lycopersicon esculentum (LEA), Morniga-G (MNA-G) and
      Helix pomatia (HPA). No significant correlation between the binding of specific
      lectins and bacterial composition was found. Fluorescently labeled lectins enable
      the visualization of glycoconjugates in the dental biofilm matrix. The
      characterization and quantification of glycoconjugates in dental biofilms require
      a combination of several lectins. For 48-h-biofilms grown in absence of sucrose,
      AAL, Calsepa, HPA, LEA, and MNA-G are recommendable.

PMID- 28748045
TI  - SigTree: A Microbial Community Analysis Tool to Identify and Visualize
      Significantly Responsive Branches in a Phylogenetic Tree.
AB  - Microbial community analysis experiments to assess the effect of a treatment
      intervention (or environmental change) on the relative abundance levels of
      multiple related microbial species (or operational taxonomic units)
      simultaneously using high throughput genomics are becoming increasingly common.
      Within the framework of the evolutionary phylogeny of all species considered in
      the experiment, this translates to a statistical need to identify the
      phylogenetic branches that exhibit a significant consensus response (in terms of
      operational taxonomic unit abundance) to the intervention. We present the R
      software package SigTree, a collection of flexible tools that make use of meta
      analysis methods and regular expressions to identify and visualize significantly
      responsive branches in a phylogenetic tree, while appropriately adjusting for
      multiple comparisons.

PMID- 28748046
TI  - Comparison of the effect of three autogenous bone harvesting methods on cell
      viability in rabbits.
AB  - Background. This study was designed to compare the viability of autogenous bone
      grafts, harvested using different methods, in order to determine the best
      harvesting technique with respect to more viable cells. Methods. In this animal
      experimental study, three harvesting methods, including manual instrument
      (chisel), rotary device and piezosurgery, were used for harvesting bone grafts
      from the lateral body of the mandible on the left and right sides of 10 rabbits.
      In each group, 20 bone samples were collected and their viability was assessed
      using MTS kit. Statistical analyses, including ANOVA and post hoc Tukey tests,
      were used for evaluating significant differences between the groups. Results. One
      way ANOVA showed significant differences between all the groups (P=0.000). Data
      analysis using post hoc Tukey tests indicated that manual instrument and
      piezosurgery had no significant differences with regard to cell viability
      (P=0.749) and the cell viability in both groups was higher than that with the use
      of a rotary instrument (P=0.000). Conclusion. Autogenous bone grafts harvested
      with a manual instrument and piezosurgery had more viable cells in comparison to
      the bone chips harvested with a rotary device.

PMID- 28748047
TI  - Immediate vs. delayed endosseous integration of maxi implants: a torque removal
      animal study.
AB  - Background. Delayed loading is one of the concerns in implant patients. Immediate
      loading can solve the problem and make patients more satisfied. The present study
      aimed to compare the removal torque of maxi implants under different loading
      (immediate and delayed) patterns. Methods. This split-mouth experimental study
      included 2 dogs. Impressions were made and then all the premolars were extracted
      under general anesthesia. After a three-month healing period, 3 implants were
      inserted in each quadrant (a total of 12 implants). Anterior and posterior
      implants (the case group) were splinted by an acrylic temporary bridge in order
      to make the middle implants (the control group) off the occlusion. The dogs were
      sacrificed after 6 weeks and bone blocks were submitted for removal torque test.
      Data were analyzed with ANOVA (P<0.05). Results. Mean torque values for the cases
      and control groups were 46.82+/-25.58 and 59.88+/-15.19, respectively (P=0.582;
      not significant). Conclusion. It may be concluded that immediate loading does not
      reduce the reverse torque values of maxi implants. This supports the advantages
      of immediate loading for maxi implants.

PMID- 28748048
TI  - Effect of different mixing methods on the bacterial microleakage of white
      Portland cement and white Mineral Trioxide Aggregate.
AB  - Background. of this study was to investigate the effect of different mixing
      methods (ultrasonic, amalgamator, and conventional) on the bacterial microleakage
      of white Portland cement (WPC) and white MTA (Tooth-colored Formula, Dentsply,
      Tulsa Dental, Tulsa, OK). Methods. A hundred human single-rooted permanent teeth
      were decoronated to obtain 14 mm of root length in all the samples. The root
      canals were cleaned, shaped and obturated. Three millimeters of each root apex
      were cut off and randomly divided into 6 groups of 15 each (3 groups for WMTA and
      3 groups for WPC, each with 3 different mixing methods) and 2 positive and
      negative control groups (each containing 5 samples). Brain-heart infusion agar
      (BHI) suspension containing the bacterial species Enterococcus faecalis (ATCC
      29212) was used for leakage assessment. Statistical analysis was carried out
      using descriptive statistics and Kaplan Mayer survival analysis with censored
      data and log rank test using SPSS 18. Statistical significance was set at P<0.05.
      Results. The survival means in PC for conventional method, amalgamator, and
      ultrasonic were 80.2+/-13.64, 78.5+/-13.46 and 84.667+/-11.42 days, with 49.13+/
      12.96, 66+/-13.32 and 69.07+/-11.5 days for MTA, respectively. The log rank test
      showed no significant differences between the three methods in each material
      (P>0.05). Conclusion. Bacterial microleakage in the studied samples was not
      significantly different in terms of the type of the mixing method.

PMID- 28748049
TI  - Effect of different nickel-titanium rotary files on dentinal crack formation
      during retreatment procedure.
AB  - Background. The aim of this study was to compare the dentinal defects caused by
      Reciproc, TF Adaptive and ProTaper Next NiTi rotary file systems during the
      retreatment procedure. Methods. A total of 150 mandibular incisors with straight
      and single root canals were included in the present study. All the root canals
      were prepared up to an apical diameter 0.40 mm using stainless steel files.
      Thirty teeth were randomly stored as the negative control group. A total of 120
      specimens were obturated with gutta-percha and AH Plus sealer using vertical
      compaction technique. Thirty specimens with root canal filling were randomly
      separated for the only-filled group. Then the teeth were randomly divided into 3
      groups; Reciproc, TF Adaptive and ProTaper Next. The retreatment procedure was
      performed with these NiTi files. Then 150 specimens were cut perpendicular to
      tooth axis at 3-, 6-, and 9-mm distances from the apex, and examined to determine
      the presence of any cracks at *25 under a stereomicroscope. Chi-squared test was
      used at 5% significance level. Results. All the tested NiTi file systems were
      found to cause significantly more dentinal defects compared to unprepared and
      only-filled groups (P<0.05). No statistically significant differences were found
      between the groups in terms of dentinal defects (P>0.05). No correlation was
      found between the slice levels and the dentinal defect distribution (P>0.05).
      Conclusion. Within the limitations of present study, all the tested NiTi file
      systems were found to cause significantly more dentinal defects compared to
      unprepared and only-filled groups.

PMID- 28748050
TI  - Assessment of facultative anaerobes from the root canals of deciduous molars: An
      in vivo study.
AB  - Background. The current research aimed to assess the prevalence of facultative
      anaerobes isolated from the root canals of deciduous molars. Methods. The present
      research enrolled 60 children in the 6-9-year age group based on clinical and
      radiographic findings. Under aseptic conditions, access cavities were prepared
      followed by collection of samples from infected root canals with the help of
      sterile paper points. The samples thus obtained were subjected for microbial
      assay. Results. It was found that Enterococcus faecalis was isolated in 30% of
      cases, Escherichia coli in 28.4%, Staphylococcus aureus in 25%, alpha-hemolytic
      Streptococci in 15% and Proteus mirabilis in 1.6% of cases. Conclusion. It was
      concluded from the results of the present study that the root canals of deciduous
      molars had predominance of facultative anaerobes, confirming its polymicrobial
      nature. This identification of microbes is crucial as it aids in understanding
      the pathogenesis of pulpal and periradicular diseases to provide effective
      antimicrobial irrigation and medicament for endodontic treatment.

PMID- 28748051
TI  - Factors affecting marginal integrity of class II bulk-fill composite resin
      restorations.
AB  - Background. Bulk-fill composite resins are a new type of resin-based composite
      resins, claimed to have the capacity to be placed in thick layers, up to 4 mm.
      This study was carried out to evaluate factors affecting gap formation in Cl II
      cavities restored using the bulk-fill technique. Methods. A total of 60 third
      molars were used in this study. Two Cl II cavities were prepared in each tooth,
      one on the mesial aspect 1 mm coronal to the CEJ and one on the distal aspect 1
      mm apical to the CEJ. The teeth were divided into 4 groups: A: The cavities were
      restored using the bulk-fill technique with Filtek P90 composite resin and its
      adhesive system and light-cured with quartz tungsten halogen (QTH) light-curing
      unit. B: The cavities were restored similar to that in group A but light-cured
      with an LED light-curing unit. C: The cavities were restored using the bulk-fill
      technique with X-tra Fil composite resin and Clearfil SE Bond adhesive system and
      light-cured with a QTH curing unit. D: The cavities were restored similar to that
      in group C but light-cured with an LED light-curing unit. The gaps were examined
      under a stereomicroscope at *60. Data were analyzed with General Linear Model
      test. In cases of statistical significance (P<0.05), post hoc Bonferroni test was
      used for further analyses. Results. The light-curing unit type had no effect on
      gap formation. However, the results were significant in relation to the composite
      resin type and margin location (P<0.001). The cumulative effects of light-curing
      unit*gingival margin and light-curing unit*composite resin type were not
      significant; however, the cumulative effect of composite rein type*gingival
      margin was significant (P=0.04) Conclusion. X-tra Fil composite exhibited smaller
      gaps compared with Filtek P90 composite with both light-curing units. Both
      composite resins exhibited smaller gaps at enamel margins.

PMID- 28748052
TI  - The effect of repeated torque tightening on total lengths of implant abutments in
      different internal implant-abutment connections.
AB  - Background. Since the misfit of crown has an important role in clinical
      performance of implant-supported prostheses, and due to the impact of the
      settling effect on misfit, the aim of this study was to investigate the impact of
      torque forces on the total lengths of narrow and short implant abutments in
      different internal implant-abutment connections. Methods. In four different
      implant-abutment connections, 8 analog implants with a normal diameter (4 mm) and
      narrow abutment (4.5 mm) were selected from groups of internal hex, internal
      octagon, morse hex 6 degrees  and morse hex 11 degrees . Each of them was mounted
      within plaster type IV, and 32 samples were obtained. Then, the amount of
      vertical displacement was measured by closing the impression copings and applying
      torques of 20 25 and 30 Ncm. This stage was repeated for the abutment. In the
      next stage, the resin pattern was built and measurements were performed after
      applying the torques mentioned. Finally, after making the frame, this stage was
      repeated, and the settling effect was statistically analyzed with ANOVA. Results.
      In the stages of impression coping, resin pattern and final prosthesis, HEXAGONE
      had significantly the highest and OCTAGONE had the lowest rates of settling, and
      the settling of morse hex 11 degrees  and 6 degrees  was between them.
      Conclusion. Octagon implant had significantly the lowest settling in various
      clinical and laboratory stages by applying different torques.

PMID- 28748053
TI  - Allogeneic stem cells derived from human exfoliated deciduous teeth (SHED) for
      the management of periapical lesions in permanent teeth: Two case reports of a
      novel biologic alternative treatment.
AB  - Stem cells are the pluripotent cells that have the capacity to differentiate into
      other specialized cells. Recently, many experiments have been conducted to study
      the potentiality of stem cells in the tissue regeneration. We report two cases
      treated utilizing stem cells from human exfoliated deciduous teeth (SHED) in the
      management of periapical lesions in permanent teeth. Two normal human deciduous
      teeth from children, 7-8 years of age, were collected to isolate stem cells. Two
      patients, one with periapical pathology alone and the other with periapical
      lesion along with an open apex in young permanent teeth, were selected for the
      study. After initial debridement of the root canals, homing of SHED was carried
      out and the access cavity was sealed using glass-ionomer cement. Clinical
      examination after 7 days, 30 days, 90 days, 180 days and 365 days revealed no
      symptoms. Closure of open apex and periapical tissue healing were observed
      radiographically at one-month review and maintained until 365-day review.
      Positive response to electric pulp testing was recorded for the treated teeth
      from the 3- to 12-month follow-ups. The treated cases demonstrated complete
      resolution of periapical radiolucency in a span of 30 days, which was faster than
      the conventional methods. SHED could be considred effective in treating the
      periapical lesions and open apex in permanent teeth.

PMID- 28748054
TI  - Autologous periodontal stem cell assistance in periodontal regeneration technique
      (SAI-PRT) in the treatment of periodontal intrabony defects: A case report with
      one-year follow-up.
AB  - Numerous animal and human studies have provided evidence supporting the belief
      that periodontal ligament stem cells (PDLSCs) can be harnessed for regeneration
      of periodontal tissues. Based on current literature on the use of ex vivo stem
      culture and associated problems, this case report describes a novel approach of
      direct application PDLSCs using stem cell assistance in periodontal regeneration
      technique (SAI-PRT) for the regeneration of intrabony periodontal defects
      bypassing ex vivo cultures. SAI-PRT has emerged as a constructive avenue in the
      treatment of periodontal osseous defects. Moreover, the current technique is less
      technique-sensitive, cost-effective and yields promising results.

PMID- 28748055
TI  - Multiple talon cusps on maxillary central incisor: A case report.
AB  - Dental anomalies affecting the teeth are relatively common. Simultaneous
      occurrence of multiple dental abnormalities in a single tooth is uncommon and
      relatively rare. One such abnormality routinely encountered in dental clinics is
      the talon cusp. It is also referred to as dens evaginatus, characterized by the
      presence of an accessory cusp-like structure projecting from the cingulum of
      anterior teeth. It has an increased predilection for maxillary teeth and
      permanent dentition. Although numerous cases of talon cusp have been reported in
      the literature, occurrence of multiple talon cusps in maxillary central incisors
      has not been found in the literature. This case report highlights the presence of
      talon cusps in maxillary anterior teeth with multiple impacted supernumerary
      teeth.

PMID- 28748056
TI  - Maxillary canine-second molar transposition: A rare case report.
AB  - Tooth transposition, which is a rare condition, is ascribed to the disturbance of
      tooth eruption and the subsequent abnormal occlusal relationships. Transpositions
      mostly involve the upper jaw and more frequently occur between the maxillary
      canine and first premolar. Herein, we present a case of a maxillary canine-second
      molar transposition in a thalassemic patient.

PMID- 28748057
TI  - Beliefs About the Cause of Schizophrenia Among Caregivers in Midwestern Nigeria.
AB  - Schizophrenia is a devastating illness with a chronic and relapsing course. While
      Western countries may endorse, biological and psychosocial causes more commonly
      than supernatural causes, non-western cultures like Nigeria in contrast, tend to
      endorse supernatural causes. Belief in supernatural causes has been reported to
      have consequences for treatment seeking behavior. This study aimed to examine the
      causes of schizophrenia reported by family members of outpatients with
      schizophrenia in a neuropsychiatric hospital in Midwestern Nigeria. In this
      study, we recruited a convenient sample of 200 consecutive caregivers of patients
      visiting the outpatient department of the Psychiatric Hospital, Benin City,
      Nigeria. These primary caregivers were unpaid relatives who provided support to
      patients. The patients were service users who fulfilled the diagnostic criteria
      of the International Classification of Disease [ICD-10; World Health Organization
      1993] for schizophrenia and had been on treatment for at least two years.
      Majority (72.0%) of caregivers endorsed supernatural causes as most important in
      the etiology of schizophrenia, while 28.0% endorsed natural causes. Every
      participant without formal education endorsed supernatural attribution. In our
      study, it was evident that participants embraced multiple causal attributions for
      schizophrenia.

PMID- 28748058
TI  - Electroconvulsive Therapy Hasn't Negative Effects on Short-Term Memory Function,
      as Assessed Using a Bedside Hand-Held Device.
AB  - Electroconvulsive therapy (ECT) is effective in the treatment of treatment
      resistant major depression. The fear of cognitive impairment after ECT often
      deters patients from choosing this treatment option. There is little reliable
      information regarding the effects of ECT on overall cognitive performance, while
      short-term memory deficits are well known but not easy to measure within clinical
      routines. In this pilot study, we examined ECT recipients' pre- and post
      treatment performances on a digital ascending number tapping test. We found that
      cognitive performance measures exhibited good reproducibility in individual
      patients and that ECT did not significantly alter cognitive performance up to 2
      hours after this therapy was applied. Our results can help patients and
      physicians make decisions regarding the administration of ECT. Digital
      measurements are recommended, especially when screening for the most common side
      effects on cognitive performance and short-term memory.

PMID- 28748059
TI  - Realizing the Promises of Telepsychiatry in Special Populations.

PMID- 28748060
TI  - A Case of Attempted Bilateral Self-Enucleation in a Patient with Bipolar
      Disorder.
AB  - Attempted and completed self-enucleation, or removal of one's own eyes, is a rare
      but devastating form of self-mutilation behavior. It is often associated with
      psychiatric disorders, particularly schizophrenia, substance induced psychosis,
      and bipolar disorder. We report a case of a patient with a history of bipolar
      disorder who gouged his eyes bilaterally as an attempt to self-enucleate himself.
      On presentation, the patient was manic with both psychotic features of
      hyperreligous delusions and command auditory hallucinations of God telling him to
      take his eyes out. On presentation, the patient had no light perception vision in
      both eyes and his exam displayed severe proptosis, extensive conjunctival
      lacerations, and visibly avulsed extraocular muscles on the right side. An
      emergency computed tomography scan of the orbits revealed small and irregular
      globes, air within the orbits, and intraocular hemorrhage. He was taken to the
      operating room for surgical repair of his injuries. Attempted and completed self
      enucleation is most commonly associated with schizophrenia and substance induced
      psychosis, but can also present in patients with bipolar disorder. Other less
      commonly associated disorders include obsessive-compulsive disorder, depression,
      mental retardation, neurosyphilis, Lesch-Nyhan syndrome, and structural brain
      lesions.

PMID- 28748061
TI  - Host Molecular Factors and Viral Genotypes in the Mother-to-Child HIV-1
      Transmission in Sub-Saharan Africa.
AB  - Maternal viral load and immune status, timing and route of delivery, viral
      subtype, and host genetics are known to influence the transmission, acquisition
      and disease progression of human immunodeficiency virus-1 (HIV-1) infection. This
      review summarizes the findings from published works on host molecular factors and
      virus genotypes affecting mother to child transmission (MTCT) in Africa and
      identifies the gaps that need to be addressed in future research. Articles in
      PubMed, Google and AIDSearch and relevant conference abstracts publications were
      searched. Accessible articles on host factors and viral genetics impacting the
      MTCT of HIV, done on African populations till 2015 were downloaded. Forty-six
      articles were found and accessed; 70% described host genes impacting the
      transmission. The most studied gene was the CCR5 promoter, followed by the CCR2
      64I found to reduce MTCT; then SDF1-3'A shown to have no effect on MTCT and
      others like the DC-SIGNR, CD4, CCL3 and IP-10. The HLA class I was most studied
      and was generally linked to the protective effect on MTCT. Breast milk
      constituents were associated to protection against MTCT. However, existing
      studies in Sub Saharan Africa were done just in few countries and some done
      without control groups. Contradictory results obtained may be due to different
      genetic background, type of controls, different socio-cultural and economic
      environment and population size. More studies are thus needed to better
      understand the mechanism of transmission or prevention.

PMID- 28748062
TI  - Analysis on the Association Among Stunting, Wasting and Underweight in Malawi: An
      Application of a Log-Linear Model for the Three-Way Table.
AB  - Childhood undernutrition is an important public health problem. Many studies have
      investigated the factors of childhood undernutrition, but not the association
      between the undernutrition indicators. This study aimed at investigating the
      association between the childhood undernutrition indicators. A loglinear model of
      cell counts of a three way table of stunting, wasting, and underweight was fitted
      based on the 2010 Malawi demographic health survey data. Interaction terms in the
      model depicted deviations from independence. A multiple correspondence analysis
      of undernutrition indicators was also plotted to have a visual impression of
      association of the undernutrition variables. A loglinear model showed that
      underweight was associated with both stunting (P<0.001), and wasting (P<0.001).
      There was no association between stunting and wasting (P=1). Furthermore there
      was no three way association of stunting, wasting and underweight (P=1). Lack of
      three way interaction of stunting, wasting and underweight means that childhood
      undernutrition multidimensional nature is still valid, and no each indicator can
      represent the other.

PMID- 28748063
TI  - Field Application of the Micro Biological Survey Method for the Assessment of the
      Microbiological Safety of Different Water Sources in Horn of Africa and the
      Evaluation of the Effectiveness of Moringa Oleifera in Drinking Water
      Purification.
AB  - Water monitoring requires expensive instrumentations and skilled technicians. In
      developing Countries as Africa, the severe economic restrictions and lack of
      technology make water safety monitoring approaches applied in developed
      Countries, still not sustainable. The need to develop new methods that are
      suitable, affordable, and sustainable in the African context is urgent. The
      simple, economic and rapid Micro Biological Survey (MBS) method does not require
      an equipped laboratory nor special instruments and skilled technicians, but it
      can be very useful for routine water analysis. The aim of this work was the
      application of the MBS method to evaluate the microbiological safety of different
      water sources and the effectiveness of different drinking water treatments in the
      Horn of Africa. The obtained results have proved that this method could be very
      helpful to monitor water safety before and after various purification treatments,
      with the aim to control waterborne diseases especially in developing Countries,
      whose population is the most exposed to these diseases. In addition, it has been
      proved that Moringa oleifera water treatment is ineffective in decreasing
      bacterial load of Eritrea water samples.

PMID- 28748064
TI  - Publication Practices and Responsible Authorship: A Review Article.
AB  - Dissemination of research findings through the publication of one's work or a
      group of contributors is an important part of the research process, as this
      allows the passing on of benefits to a much wider community. In whatever
      evocative form this dissemination may take, the onus lies on the author(s) to
      ensure adherence to the code of ethics as it pertains to the integrity of the
      information being put out. We publish because we want our findings to be adapted
      into practice and application, or in some cases may be relevant to policy makers
      in decision-making. To a large extent in the field of academia, successful
      publication improves opportunities for academic funding and promotion whilst
      enhancing scientific and scholarly achievement and repute. A situation may be
      compromised where intellectual contributions to a scientific investigation do not
      adhere to the four key guidelines of scholarship, authorship, approval and
      agreement as well as the protocols of ensuring good publication ethics. The
      objective of this review is to lay emphasis on universal standards for manuscript
      authorship and to fostering good practices. This in our view will bring
      authorship credit and accountability to the attention of our colleagues and
      readers at large. To achieve this, a systematic and critical review of the
      literature was undertaken. Electronic databases, academic journals and books from
      various sources were accessed. Several key search terms relating to responsible
      authorship, common authorship malpractices, conflict of interest, universal
      publication guidelines and other authorship related issues, were used. Only
      references deemed useful from relevant texts and journal articles were included.
      In this paper, the authors have sought to highlight the pitfalls researchers
      sometimes entangle themselves within an act of compromise thereby impinging on
      the ethical and professional responsibilities for the content of a paper under
      consideration. This article presents the case that authorship has a strong
      currency that brings not only personal satisfaction but also career rewards based
      on publication counting. In all cases described here, a universal standard for
      manuscript authorship will be critical in fostering good practices. As you write
      and review manuscripts, keep these good practices in mind, and consider ways to
      bring authorship credit and accountability to the attention of your colleagues
      and readers.

PMID- 28748065
TI  - Why Publishing the Journal of Public Health in Africa.

PMID- 28748066
TI  - Gottfried Wilhelm Osann (1833, 1836) on Simultaneous Color Contrast: Translation
      and Commentary.
AB  - Gottfried Wilhelm Osann (1796-1866) was a German scientist most renowned for his
      work in chemistry and physics. However, inspired by Goethe's work on color, he
      published a paper on simultaneous color contrast in 1833 using a method that is
      similar to that of later authors: reflection of an achromatic spot from an angled
      piece of glass. He wrote at least four more papers on color contrasts, in 1836
      using essentially the same method as credited to others. We provide a description
      and translation of Osann's 1833 paper and the relevant part of his 1836 paper,
      say why these papers are interesting and important, give some biographical
      information about Osann, comment on the fate of Osann's papers, and describe
      Osann's other papers on color.

PMID- 28748067
TI  - A Matched Comparison Across Three Different Sensory Pairs of Cross-Modal Temporal
      Recalibration From Sustained and Transient Adaptation.
AB  - Sustained exposure to an asynchronous multisensory signal causes perceived
      simultaneity to shift in the direction of the leading component of the adapting
      stimulus. This is known as temporal recalibration, and recent evidence suggests
      that it can occur very rapidly, even after a single asynchronous audiovisual (AV)
      stimulus. However, this form of rapid recalibration appears to be unique to AV
      stimuli, in contrast to recalibration following sustained asynchronies which
      occurs with audiotactile (AT) and visuotactile (VT) stimuli. This study examines
      temporal recalibration to AV, VT and AT asynchrony with spatially collocated
      stimuli using a design that produces both sustained and inter-trial recalibration
      by combining the traditional sustained adaptation approach with an inter-trial
      analysis of sequential dependencies in an extended test period. Thus, we compare
      temporal recalibration to both sustained and transient asynchrony in three
      crossmodal combinations using the same design, stimuli and observers. The results
      reveal that prolonged exposure to asynchrony produced equivalent temporal
      recalibration for all combinations: AV, AT and VT. The pattern for rapid, inter
      trial recalibration was very different. Rapid recalibration occurred strongly for
      AV stimuli, weakly for AT and did not occur at all for VT. For all sensory
      pairings, recalibration from sustained asynchrony decayed to baseline during the
      test phase while inter-trial recalibration was present and stable throughout
      testing, suggesting different mechanisms may underlie adaptation at long and
      short timescales.

PMID- 28748068
TI  - A Primer on Bayesian Analysis for Experimental Psychopathologists.
AB  - The principal goals of experimental psychopathology (EPP) research are to offer
      insights into the pathogenic mechanisms of mental disorders and to provide a
      stable ground for the development of clinical interventions. The main message of
      the present article is that those goals are better served by the adoption of
      Bayesian statistics than by the continued use of null-hypothesis significance
      testing (NHST). In the first part of the article we list the main disadvantages
      of NHST and explain why those disadvantages limit the conclusions that can be
      drawn from EPP research. Next, we highlight the advantages of Bayesian
      statistics. To illustrate, we then pit NHST and Bayesian analysis against each
      other using an experimental data set from our lab. Finally, we discuss some
      challenges when adopting Bayesian statistics. We hope that the present article
      will encourage experimental psychopathologists to embrace Bayesian statistics,
      which could strengthen the conclusions drawn from EPP research.

PMID- 27853520
TI  - dot-app: a Graphviz-Cytoscape conversion plug-in.
AB  - dot-app is a Cytoscape 3 app that allows Cytoscape to import and export Graphviz
      (.dot, .gv) files, also known as DOT files due to the .dot extension and their
      conformance to the DOT language syntax. The DOT format was originally created in
      the early 2000s to represent graph topologies, layouts and formatting. DOT
      encoded files are produced and consumed by a number of open-source graph
      applications, including Graphviz, Gephi, Tulip, and others. While DOT-based graph
      applications are popular, they emphasize general graph layout and styling over
      the topological and semantic analysis functions available in domain-focused
      applications such as Cytoscape. While domain-focused applications have easy
      access to large networks (10,000 to 100,000 nodes) and advanced analysis and
      formatting, they do not have as many styling options as the Graphviz software
      suite. dot-app enables the interchange of networks between Cytoscape and DOT
      compatible applications so that users can benefit from the features of both. dot
      app was first deployed to the Cytoscape App Store in August 2015, has since
      registered more than 1,200 downloads, and has been highly rated by more than 20
      users.

PMID- 28443186
TI  - General guidelines for biomedical software development.
AB  - Most bioinformatics tools available today were not written by professional
      software developers, but by people that wanted to solve their own problems, using
      computational solutions and spending the minimum time and effort possible, since
      these were just the means to an end. Consequently, a vast number of software
      applications are currently available, hindering the task of identifying the
      utility and quality of each. At the same time, this situation has hindered
      regular adoption of these tools in clinical practice. Typically, they are not
      sufficiently developed to be used by most clinical researchers and practitioners.
      To address these issues, it is necessary to re-think how biomedical applications
      are built and adopt new strategies that ensure quality, efficiency, robustness,
      correctness and reusability of software components. We also need to engage end
      users during the development process to ensure that applications fit their needs.
      In this review, we present a set of guidelines to support biomedical software
      development, with an explanation of how they can be implemented and what kind of
      open-source tools can be used for each specific topic.

PMID- 28748071
TI  - Fish burger enriched by olive oil industrial by-product.
AB  - Oil industry produces large volume of waste, which represents a disposal and a
      potential environmental pollution problem. Nevertheless, they are also promising
      sources of compounds that can be recovered and used as valuable substances. The
      aim of this work is to exploit solid olive by-products, in particular dry olive
      paste flour (DOPF) coming from Coratina cultivar, to enrich fish burger and
      enhance the quality characteristics. In particular, the addition of olive by
      products leads to an increase of the phenolic content and the antioxidant
      activity; however, it also provokes a deterioration of sensory quality.
      Therefore, to balance quality and sensory characteristics of fish burgers, three
      subsequent phases have been carried out: first, the quality of DOPF in terms of
      phenolic compounds content and antioxidant activity has been assessed; afterward,
      DOPF has been properly added to fish burgers and, finally, the formulation of the
      enriched fish burgers has been optimized in order to improve the sensory quality.
      Results suggested that the enriched burgers with 10% DOPF showed considerable
      amounts of polyphenols and antioxidant activity, even though they are not very
      acceptable from the sensory point of view. Pre-treating DOPF by
      hydration/extraction with milk, significantly improved the burger sensory quality
      by reducing the concentration of bitter components.

PMID- 28748072
TI  - The Evaluation of saccharose replacing by adding stevioside-maltodextrin mixture
      on the physicochemical and sensory properties of Naanberenji (an Iranian
      confectionary).
AB  - Stevia is a natural, non-nutritive sweetener can replace sugar in your diet to
      control diabetes and aid in weight loss. Naanberenji, an Iranian traditional
      cookie, is a well-reputed confectionary containing high sucrose and calorie
      value, for this reason its consumption in healthy diet has been restricted. In
      this study, the effect of sucrose replacement by stevioside-maltodextrin mixture
      on physicochemical properties of Naanberenji was evaluated in four replacing
      levels including 25%, 50%, 75%, and 100%. Results of texture evaluation revealed
      that hardness increases due to adding stevioside-maltodextrin (p < .05). Color
      analysis also showed that browning index by adding more mixture reduced.
      Moreover, the results of sensory analysis showed that treatment containing 25%
      stevioside-maltodextrin was the most similar sample to control and 23.06%
      reduction in sugar consumption achieved in this level of replacement. Therefore,
      its physicochemical properties (peroxide, acidity, chemical compounds, and
      hardness) were measured. According to the results, calorie amount decreased by
      7.27 %. While there was no significant difference in the acidity of the aforesaid
      sample, peroxide results exhibited significant differences. Analysis of
      Farinograph plot revealed more water binding in comparison to control sample.

PMID- 28748073
TI  - Consumer-orientated development of hybrid beef burger and sausage analogues.
AB  - Hybrid meat analogues, whereby a proportion of meat has been partially replaced
      by more sustainable protein sources, have been proposed to provide a means for
      more sustainable diets in the future. Consumer testing was conducted to determine
      consumer acceptability of different formulations of Hybrid beef burgers and pork
      sausages in comparison with both meat and meat-free commercial products.
      Acceptability data were generated using the 9-point hedonic scale. Check-all-that
      apply (CATA) questioning was used to determine the sensory attributes perceived
      in each product as well as information on the attributes of consumers' ideal
      products. It was identified that Hybrid products were generally well liked among
      consumers and no significant differences in consumer acceptability (p > .05) were
      identified between Hybrid and full meat products, whereas meat-free products were
      found to be less accepted. However, Hybrid sausages received higher acceptability
      scores (6.00-6.51) than Hybrid burgers (5.84-5.92) suggesting that format may
      have a large impact on consumer acceptability of Hybrid products. Correspondence
      Analysis (CA) indicated that Hybrid products were grouped with meat products in
      their sensory attributes. Penalty analysis found that a "meaty flavor" was the
      largest factor driving consumer acceptability in both burgers and sausages.
      Cluster analysis of consumer acceptability data identified key differences in
      overall acceptability between different consumer groups (consumers who only eat
      meat products and consumers who eat both meat and meat-free products). The Hybrid
      concept was found to bridge the acceptability gap between meat and meat-free
      products; however, further product reformulation is required to optimize consumer
      acceptability.

PMID- 28748074
TI  - Antibacterial electrospun chitosan-based nanofibers: A bacterial membrane
      perforator.
AB  - This study investigates the antibacterial action of chitosan-based nanofibers
      (CNFs) obtained by the electrospinning process on the permeability of bacterial
      membranes. The bactericidal efficiency of CNFs was first determined against Gram
      negative Escherichia coli and Salmonella Typhimurium, and Gram-positive
      Staphylococcus aureus and Listeria innocua bacteria as a baseline. The results
      strongly suggest that CNFs interact with the negatively charged bacterial cell
      wall causing membrane rupture and inducing leakage of intracellular components
      among which are proteins and DNA. Results clearly indicate that the release of
      such components after contact with CNFs is an indication of membrane
      permeabilization and perforation, as pore formation was observed in transmission
      electron microscopy (TEM). This work suggests a plausible antibacterial mechanism
      of action of CNFs and also provides clear evidence in favor of chitosan as a
      bacterial membrane disruptor and perforator. As a result, CNFs can find promising
      applications as bioactive food packaging materials capable to extend shelf life
      of food products while inhibiting the spread of alteration flora and foodborne
      pathogens.

PMID- 28748075
TI  - Physicochemical and sensory attributes assessment of functional low-fat yogurt
      produced by incorporation of barley bran and Lactobacillus acidophilus.
AB  - The aim of this study was to analyze the effect of different amounts of barley
      bran (0.3%, 0.6%, 0.9%, and 1.2%) on the viability of Lactobacillus acidophilus
      and the physicochemical and sensory properties of low-fat yogurt during storage
      period (28 days). Results showed that L. acidophilus number and viscosity in
      samples containing barley bran was significantly higher than the control group (p
      < .05). High levels of barley bran (1.2%) decreased sensory prosperity scores and
      led to viscosity increment; although sensory prosperity scores of samples
      containing 0.6% barley bran did not show significant difference with control
      sample, while the number of L. acidophilus in this treatment was higher than
      minimal acceptable level (106 CFU/g). Therefore, level of 0.6% of barley bran is
      recommended for symbiotic yogurt production. According to the present study, a
      positive correlation was observed between barley bran concentrations in the
      yogurt with L. acidophilus number.

PMID- 28748076
TI  - Allergens labeling on French processed foods - an Oqali study.
AB  - The French Observatory of Food Quality (Oqali) aims at collecting all nutritional
      data provided on labels of processed foods (nutritional information and
      composition), at branded products level, in order to follow nutritional labeling
      changes over time. This study carries out an overview of allergens labeling
      frequencies by distinguishing allergens used in recipes from those listed on
      precautionary statements, for the fourteen allergen categories for which labeling
      is mandatory according to European legislation. 17,309 products were collected,
      between 2008 and 2012, from 26 food categories. Products were classified per
      family and type of brand (national brands, retailer brands, entry-level retailer
      brands, hard discount, and specialized retailer brands). Allergenic ingredients
      were identified from ingredients lists and precautionary statements. 73% of the
      17,309 products studied contained at least one allergen in their ingredients list
      and 39% had a precautionary statement for one or more allergens. Milk (53%),
      gluten (41%), and egg (22%) were the most commonly used allergens in ingredients
      lists. For precautionary statement, nuts (20%), egg (14%), peanut (13%), soybean
      (12%), and milk (11%) were the most common allergens listed. Precautionary
      statement was most frequently found among first-price products (hard discount and
      entry-level retailer brands). National brands seemed to use it less frequently.
      For all these results, differences depended both on food categories and allergen
      categories. This study will enable to follow allergens labeling and their use as
      ingredients over time, particularly by assessing an hypothetical increase in
      allergens presence in processed food.

PMID- 28748077
TI  - Exploring the flavor life cycle of beers with varying alcohol content.
AB  - Decreasing alcohol in beer and increasing the pleasure of lower alcohol beers is
      a potential way to limit total alcohol consumption. Consumers' willingness to
      drink alcohol-reduced beers is mainly limited by unfavorable flavor
      characteristics that arise during consumption. To investigate the temporal flavor
      dominance during consumption, we analyzed the five most dominant beer flavors
      from nine different beers among three types of beer with varying alcohol content
      to assess the Flavor Life Cycle. Results show that beers with different alcohol
      content displayed similar flavor dominance (e.g., bitterness) and displayed
      differences in worty-off flavor, malty flavor, and astringency. In alcohol-free
      beers, worty-off flavor was most pronounced in dominating between 5 and 30 s and
      malty flavor increased after swallowing. For bitterness and astringency, higher
      alcohol content resulted in higher flavor dominance, especially prior to
      swallowing (<=40 sec). Based on these findings, we provide some brief advice to
      minimize unfavorable flavor experience during consumption of beer with lower
      alcohol. For now, consumers who want to enjoy beers with lower alcohol should
      consider flavor changes and focus on the favored and defocus on the less favored
      flavors.

PMID- 28748078
TI  - Determination of the protein quality of cooked Canadian pulses.
AB  - A study to determine the protein digestibility-corrected amino acid score and
      protein efficiency ratio of nine different cooked Canadian pulse classes was
      conducted in support of the establishment of protein quality claims in Canada and
      the United States. Split green and yellow pea, whole green lentil, split red
      lentil, Kabuli chickpea, navy bean, pinto bean, light red kidney bean, and black
      bean were investigated. Protein digestibility-corrected amino acid score (PDCAAS)
      and the protein efficiency ratio (PER) were determined using the appropriate
      rodent models. All pulses had high digestibility values, >70%, with PDCAAS values
      greater than 0.5, thereby qualifying as a quality protein in the United States,
      but only navy beans qualified as a good source of protein. All pulses except
      whole green lentils, split red lentils, and split green peas would qualify as
      sources of protein with protein ratings between 20 and 30.4 in Canada. These
      findings support the use of pulses as protein sources in the regulatory context
      of both the United States and Canada.

PMID- 28748079
TI  - Oxidative stability of chilled broiler breast meat as affected by dietary
      supplementation with rosemary (Rosmarinus officinalis L.) powder and vitamin E.
AB  - The aim of the present study was to evaluate the effect of rosemary (Rosmarinus
      officinalis L.) powder and vitamin E, as feed additives combined at different
      levels, on oxidative stability of broiler meat up to 14th day after chilling. A
      total of 270 1-day-old male chicks of Ross 308 strain were randomly assigned to
      nine dietary groups with three replicates having 10 birds each. Diets were
      supplemented with 0, 0.5, or 1.0% of rosemary (R) powder and 0, 100, or 200 mg/kg
      of vitamin E (alpha-tocopherol acetate; VitE) according to the following
      treatments: T1 - control basal diet (0R + 0VitE); T2 - 0R + 100VitE; T3 - 0R +
      200VitE; T4 - 0.5R + 0VitE; T5 - 0.5R + 100VitE; T6 - 0.5R + 200VitE; T7 - 1.0R +
      0VitE; T8 - 1.0R + 100VitE; and T9 - 1.0R + 200VitE. At day 42, two birds of each
      replicate were slaughtered and the length and weight of cecum was recorded.
      Carcasses and their economically valuable parts were also weighted and broiler
      breast refrigerated at 4 degrees C for 14 days. At day 0, 4, 7, and 14 of storage
      the malondialdehyde (MDA) content of breast meat was evaluated. After 4 days of
      storage, meat MDA contents of the T5 (0.43 mg/kg) and T9 (0.41 mg/kg) were lower
      than control group (T1: 0.55 mg/kg; p < .05). On day 7, groups supplemented with
      rosemary or VitE alone showed similar MDA contents (p > .05) than control. On day
      14, lower (p < .05) MDA contents than T1 were observed in all groups except for
      broilers fed diet supplemented only with vitamin E. No effects were observed
      between treatments on the relative weight of the several carcass traits, however,
      VitE influenced (p < .05) the weight and size of cecum. Based on our findings,
      the combination of rosemary powder and vitamin E at different levels in diet is
      useful to limit the lipid oxidation of chilled chicken meat.

PMID- 28748080
TI  - Formulation and nutritional evaluation of a healthy vegetable soup powder
      supplemented with soy flour, mushroom, and moringa leaf.
AB  - The research study was conducted to develop a healthy vegetables soup powder
      supplemented with soy flour, mushroom, moringa leaf and compare its nutritional
      facts with locally available soup powders. Proximate analysis and sensory
      evaluation were done by standard method. In this study, moisture, ash, protein,
      fat, fiber, carbohydrate, and energy content were ranged from 2.83% to 5.46%,
      9.39% to 16.48%, 6.92% to 16.05%, 4.22% to 6.39%, 0.22% to 1.61%, 58.81% to
      75.41%, and 337.42 to 386.72 kcal/100 g, respectively. Highest content of vitamin
      D, minerals, protein, and fiber and lowest content of moisture, fat, and
      carbohydrate were found in the presently developed soy-mushroom-moringa soup
      powder compare to locally available soup powders. Vitamin C was also found
      significantly higher than locally available soup powders S1, S2, and S3. Heavy
      metals were not found in any of the soup powders. On the sensory and
      microbiological point of view, the presently developed soup powder was found
      highly acceptable up to 6 months. So, the developed soy-mushroom-moringa soup
      powder is nutritionally superior to locally available soup powders and sufficient
      to meet day-to-day nutritional requirements as a supplement.

PMID- 28748081
TI  - Comparison of two sources of iodine delivery on breast milk iodine and maternal
      and infant urinary iodine concentrations in southern Ethiopia: A randomized
      trial.
AB  - Iodine deficiency during pregnancy and lactation could expose the infant to
      severe iodine deficiency disorders. A randomized supplementation trial among
      rural lactating women was conducted in Sidama zone, southern Ethiopia, to compare
      the methods of iodine delivery on breast milk iodine, and on maternal and infant
      urinary iodine concentrations. Women were randomly assigned either to receive 225
      MUg iodine as potassium iodide capsule daily for 6 months or 450 g of
      appropriately iodized salt (30-40 MUg I as KIO3/g of salt) weekly for household
      consumption for 6 months. Breast milk iodine concentration (BMIC) and maternal
      and infant urinary iodine concentration (UIC) were measured at baseline and at 6
      months. The women did not differ in BMIC and UIC, and infants did not differ in
      UIC in a time by treatment interaction. Median (IQR, interquartile range, IQR)
      BMIC at baseline was 154 [43, 252] MUg/L and at 6 months was 105 [36, 198] MUg/L,
      maternal UIC at baseline was 107 [71, 161] MUg/L and at 6 months was 130 [80,
      208] MUg/L; infant UIC at baseline was 218 [108, 356] MUg/L and at 6 months was
      222 [117, 369] MUg/L. Significant correlations among the three variables were
      obtained in both groups at both times. We conclude that for lactating women an
      adequate amount of appropriately iodized salt (30-40 MUg I/g) had similar effects
      as a daily supplement of 225 MUg I on BMIC and on maternal and infant UIC.

PMID- 28748082
TI  - Delphinidin 3-rutinoside-rich blackcurrant extract ameliorates glucose tolerance
      by increasing the release of glucagon-like peptide-1 secretion.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin that is secreted from
      enteroendocrine L-cells. Dietary factor-stimulation of endogenous GLP-1 is a
      promising strategy for increasing the action of GLP-1. Recent studies have shown
      that berries rich in anthocyanins improve insulin sensitivity and reduce the risk
      of type 2 diabetes. Our previous study found that the anthocyanin delphinidin 3
      rutinoside (D3R) significantly increases GLP-1 secretion in GLUTag cells
      (enteroendocrine L cell line). Blackcurrants are berries that contain high levels
      of anthocyanins, particularly D3R. Pre-administered blackcurrant extract (BCE) 5
      mg/kg body weight (1 mg D3R/kg) significantly ameliorated glucose tolerance after
      intraperitoneal glucose injection in rats by stimulating the secretion of GLP-1
      and subsequently inducing insulin secretion. D3R did not break down significantly
      in the gastrointestinal tract for at least 45-60 min after BCE was administered,
      suggesting that BCE-induced GLP-1 secretion is mainly mediated by D3R and not its
      degradation products. These findings demonstrate the novel biological function of
      D3R-rich BCE as a GLP-1 secretagogue. An increase in endogenous GLP-1 secretion
      induced by BCE may help to reduce the dosages of diabetic medicines and prevent
      diabetes.

PMID- 28748083
TI  - Lactadherin orthologs inhibit migration of human, porcine and murine intestinal
      epithelial cells.
AB  - Lactadherin was originally described due to its appearance in milk, but is
      abundantly expressed especially by professional and nonprofessional phagocytes.
      The proteins has been shown to have a multitude of bioactive effects, including
      inhibition of inflammatory phospholipases, induction of effero- and phagocytosis,
      prevent rotavirus induced gastroenteritis, and modulate intestinal homeostasis by
      regulating epithelial cell migration. The level of expression seems to be
      important in a row of serious pathologies linked to the intestinal epithelial
      barrier function, vascular- and autoimmune disease. This study examines the
      ability of lactadherin to modulate migration of intestinal epithelium. A cell
      exclusion assay is used to quantify the ability of human, bovine and murine
      lactadherin orthologs to affect migration of primary small intestine epithelium
      cells. Previous reports show that recombinant murine lactadherin stimulate rat
      small intestine cell migration. The present study could not confirm this.
      Conversely, 10 MUg/ml lactadherin inhibits migration. Therefore, as lactadherins
      enteroprotective properties is well established using in vivo models we conclude
      that the protective effects are linked to lactadherins ability operate as an
      opsonin, or other modulating effects, and not a direct lactadherin-cell induction
      of migration. Thus, the molecular mechanism behind the enteroprotective role of
      lactadherin remains to be established.

PMID- 28748084
TI  - Mechanical damage to green and red lentil seeds.
AB  - In this research, the breakage susceptibility of two classes of lentil (green and
      red) was evaluated as affected by impact energy and seed moisture content. The
      experiments were conducted at impact energies of 0.1, 0.2 and 0.3 J, and moisture
      contents of 10, 12.5, 15, 17.5, 20 and 25% (wet basis). Results showed that red
      lentil seeds had more breakage than green seeds and the difference in breakage
      percentage between green and red lentil seeds was significant at 0.01% level
      according to analysis of variance (p < .01). Percentage breakage of both green
      and red lentil seeds increased as the energy of impact increased. With increasing
      the seed moisture content of the both green and red lentils, the breakage
      percentage of seeds decreased. The average values of seeds breakage green and red
      lentil seeds varied from 100 to 67.7% and from 100 to 93.1%, respectively, as the
      seeds moisture content increased from 10 to 25%. The optimum seed moisture at
      which minimum damage was observed was 17.5% for green lentil and 15% for red
      lentil. Mathematical relationships composed of lentil seeds moisture content and
      energy of impact were developed for accurate description of the breakage
      percentage of green and red lentil seeds under impact loading.

PMID- 28748085
TI  - Fermentation induced changes in volatile components of African oil bean
      (Pentaclethra macrophylla Benth) seeds.
AB  - Fermented African oil bean (Pentaclethra macrophylla Benth) seed also referred to
      as "Ugba" is a known delicacy, mainly consumed by Africans. Human migration has
      also led to the introduction of this delicacy into most European and American
      countries. This study shows the changes in volatile components of African oil
      bean (P. macrophylla Benth) seed at different stages of fermentation. A quantity
      of 0.3 kg each of dehulled and sliced raw sample and cooked unfermented sample
      were separately ground, while 2 and 4 days fermented samples obtained by
      inoculating 0.6 kg of cooked, sliced and washed sample with 0.5 g of 4 days
      fermented seed was divided into two of 0.3 kg each and ground at the second and
      fourth day of fermentation. GC-MS analyses of the volatile components showed 9,12
      Octadecadienoic acid (Z,Z)- and its esters as highest in raw seed, with total
      percentage concentration of 96.301, while 9-Octadecenoic acid, methyl ester, (E)-
      was highest in cooked unfermented seed, with percentage concentration 55.204.
      Phenol, 2-methoxy-3-(2-propenyl)- and its esters were the highest observed in
      cooked 2 days fermented seed, with total percentage concentration of 50.596,
      while 9-Octadecenoic acid (Z)-, methyl ester was highest in cooked 4 days
      fermented seed with percentage concentration of 67.788. Aside from softening the
      delicacy, a 4 days chance fermentation of cooked P. macrophylla Benth seed also
      reduces the eight component lipids present in the cooked unfermented seed to a
      more nutriceutical three component lipids (Hexadecanoic acid methyl ester, 9
      Octadecenoic acid (Z)-methyl ester and Methyl stearate).

PMID- 28748086
TI  - Area Health Education Center (AHEC) programs for rural and underrepresented
      minority students in the Alabama Black Belt.
AB  - BACKGROUND: This paper evaluated the implementation West Central Alabama Area
      Health Education Center programs for high school students in grades 9-12 through
      participant-reported evaluations and feedback during the  September 1st, 2013 to
      August 31st, 2014 fiscal year. The programs targeted racial/ethnic minorities
      and/or rural individuals interested in pursuing a career as a healthcare provider
      in medically underserved counties of Alabama. METHODS: Students participated in
      enrichment activities related to prospective health careers that included:
      successful college preparedness, knowledge about health careers, and the types of
      primary care health professions that are needed in underserved Alabama
      communities. The curriculum studied 593 (ACT preparation: n = 172, AHEC 101: n =
      56, FAFSA: n = 109, Health Career Exploration: n = 159, College Career Readiness:
      n = 67, Dixie Scholars NERD: n = 30) baseline measures for the programs to
      evaluate effectiveness when rated by participants both quantitatively and
      qualitatively. RESULTS: Interactive activities with video incorporation, hands-on
      experiences, and group discussions paired with student motivation and interest in
      specific health career-related activities provided the highest program ratings.
      CONCLUSIONS: It is important to use a variety of successful program strategies
      when forming healthcare workforce development interventions. Student evaluations
      can help adapt methods for future program implementation to ultimately achieve
      strategies for health professional recruitment, training, and retention in areas
      that lack access to quality healthcare.

PMID- 28748087
TI  - Antimicrobial effects of lysophosphatidylcholine on methicillin-resistant
      Staphylococcus aureus.
AB  - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is an important
      health care-associated and community-associated pathogen and causes a large
      number of infections worldwide. For the purpose of application to topical
      treatment of MRSA infection, we examined the antimicrobial effects of
      lysophosphatidylcholine (LPC) on MRSA strains. We also investigated the
      combination effect of LPC and gentamicin on MRSA growth. METHODS: The LPC minimum
      inhibitory concentrations (MIC) for Gram-positive (S. aureus, Staphylococcus
      epidermidis, and Streptococcus pneumoniae) and Gram-negative (Escherichia coli,
      Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa) bacteria
      were measured by the broth microdilution method. The mechanism of LPC-mediated
      MRSA killing was investigated by membrane permeability analysis with DiSC3(5)
      fluorescence and growth curve analysis. Lastly, the effects of LPC on gentamicin
      induced bactericidal activity were determined in combination treatment studies
      with 15 gentamicin-resistant MRSA isolates from the skin, nose, or ears. RESULTS:
      The LPC MIC for Gram-positive bacteria varied between 32 ug/ml and >2048 ug/ml,
      whereas that for all Gram-negative bacteria was >2048 ug/ml. Consistently,
      membrane permeability analysis showed that LPC was substantially more effective
      in inducing membrane permeability in Gram-positive bacteria than in Gram-negative
      counterparts. Growth curve analysis in cotreatment studies demonstrated that LPC
      has intrinsic bactericidal effects and can also potentiate gentamicin sensitivity
      in resistant MRSA strains. CONCLUSIONS: Our study demonstrates that LPC exhibits
      intrinsic antimicrobial effects and can enhance the antimicrobial effects of
      gentamicin for resistant MRSA strains, suggesting that LPC may be a beneficial
      additive in topical antibiotics for superficial skin infections.

PMID- 28748088
TI  - Modeling risk for developing drug resistant bacterial infections in an MDR-naive
      critically ill population.
AB  - PURPOSE: To create a model predictive of an individual's risk of developing a de
      novo multidrug-resistant (MDR) infection while in the intensive care unit (ICU).
      METHODS: This is a case-control study in which 189 ICU patients diagnosed with
      their first infection with an MDR organism were compared on the basis of
      demographic, past medical and clinical variables to randomly selected ICU
      patients without such an infection, era-matched in a 2:1 ratio. A prediction tool
      was derived using multivariate logistic regression. RESULTS: Five features
      remained predictive of developing an infection with a drug-resistant pathogen:
      hospitalization within a year [adjusted odds ratio (OR) 2.14], chronic
      hemodialysis (3.86), underlying oxygen-dependent pulmonary disease (1.86),
      endotracheal intubation within 24 h (2.46) and reason for ICU admission
      (respiratory failure 2.89, non-respiratory failure, non-shock presentation 1.85).
      Using a scoring system (0-7 points) based on the adjusted OR, risk categories
      were derived (low: 0-2 points, intermediate: 3-4 points and high risk: 5-7
      points). The negative predictive value at a score cutoff of 2 is excellent
      (88.9%). CONCLUSIONS: A clinical prediction rule comprised of five easily
      measured ICU variables reasonably discriminates between patients who will develop
      their first MDR infection versus those who will not.

PMID- 28748090
TI  - Erratum: Defective T-cell control of Epstein-Barr virus infection in multiple
      sclerosis.
AB  - [This corrects the article DOI: 10.1038/cti.2016.87.].

PMID- 28748091
TI  - The tetravalent formulation of domain III-capsid proteins recalls memory B- and T
      cell responses induced in monkeys by an experimental dengue virus infection.
AB  - Tetra DIIIC is a vaccine candidate against dengue virus (DENV) composed by four
      chimeric proteins that fuse the domain III of the envelope protein of each virus
      to the corresponding capsid protein. Containing B- and T-cell epitopes, these
      proteins form aggregates after the incubation with an immunostimulatory
      oligodeoxynucleotide, and their tetravalent formulation induces neutralizing
      antibodies and cellular immune response in mice and monkeys. Also, Tetra DIIIC
      protects mice after challenge with each DENV, and the monovalent formulation
      obtained from DENV-2 protects monkeys upon homologous viral challenge. However,
      in the last years, new evidences have arisen regarding domain III of DENV
      envelope protein as irrelevant target for neutralizing antibodies in humans.
      Nevertheless, vaccination with domain III induces a neutralizing antibody
      response that confers protection against re-infection. In addition, it has been
      demonstrated that the induction of a cellular immune response is essential to
      protect during the infection. This response can also avoid severe manifestations
      of dengue disease, associated to the antibody-dependent enhancement of the
      infection. In this study, we observed that Tetra DIIIC was able to boost the
      antiviral and neutralizing antibody responses previously generated in monkeys
      during an experimental DENV infection, demonstrating that domain III is targeted
      by B cells during the viral infection. Additionally, Tetra DIIIC successfully
      boosted the cellular immune response generated by the viruses, probably against T
      cells epitopes in the capsid proteins. These results highlight the functionality
      of Tetra DIIIC as a vaccine candidate against DENV.

PMID- 28748089
TI  - The role of nanotechnology in the treatment of viral infections.
AB  - Infectious diseases are the leading cause of mortality worldwide, with viruses in
      particular making global impact on healthcare and socioeconomic development. In
      addition, the rapid development of drug resistance to currently available
      therapies and adverse side effects due to prolonged use is a serious public
      health concern. The development of novel treatment strategies is therefore
      required. The interaction of nanostructures with microorganisms is fast
      revolutionizing the biomedical field by offering advantages in both diagnostic
      and therapeutic applications. Nanoparticles offer unique physical properties that
      have associated benefits for drug delivery. These are predominantly due to the
      particle size (which affects bioavailability and circulation time), large surface
      area to volume ratio (enhanced solubility compared to larger particles), tunable
      surface charge of the particle with the possibility of encapsulation, and large
      drug payloads that can be accommodated. These properties, which are unlike bulk
      materials of the same compositions, make nanoparticulate drug delivery systems
      ideal candidates to explore in order to achieve and/or improve therapeutic
      effects. This review presents a broad overview of the application of nanosized
      materials for the treatment of common viral infections.

PMID- 28748092
TI  - A focused ultrasound treatment system for moving targets (part I): generic system
      design and in-silico first-stage evaluation.
AB  - BACKGROUND: Focused ultrasound (FUS) is entering clinical routine as a treatment
      option. Currently, no clinically available FUS treatment system features
      automated respiratory motion compensation. The required quality standards make
      developing such a system challenging. METHODS: A novel FUS treatment system with
      motion compensation is described, developed with the goal of clinical use. The
      system comprises a clinically available MR device and FUS transducer system. The
      controller is very generic and could use any suitable MR or FUS device. MR image
      sequences (echo planar imaging) are acquired for both motion observation and
      thermometry. Based on anatomical feature tracking, motion predictions are
      estimated to compensate for processing delays. FUS control parameters are
      computed repeatedly and sent to the hardware to steer the focus to the
      (estimated) target position. All involved calculations produce individually known
      errors, yet their impact on therapy outcome is unclear. This is solved by
      defining an intuitive quality measure that compares the achieved temperature to
      the static scenario, resulting in an overall efficiency with respect to
      temperature rise. To allow for extensive testing of the system over wide ranges
      of parameters and algorithmic choices, we replace the actual MR and FUS devices
      by a virtual system. It emulates the hardware and, using numerical simulations of
      FUS during motion, predicts the local temperature rise in the tissue resulting
      from the controls it receives. RESULTS: With a clinically available monitoring
      image rate of 6.67 Hz and 20 FUS control updates per second, normal respiratory
      motion is estimated to be compensable with an estimated efficiency of 80%. This
      reduces to about 70% for motion scaled by 1.5. Extensive testing (6347 simulated
      sonications) over wide ranges of parameters shows that the main source of error
      is the temporal motion prediction. A history-based motion prediction method
      performs better than a simple linear extrapolator. CONCLUSIONS: The estimated
      efficiency of the new treatment system is already suited for clinical
      applications. The simulation-based in-silico testing as a first-stage validation
      reduces the efforts of real-world testing. Due to the extensible modular design,
      the described approach might lead to faster translations from research to
      clinical practice.

PMID- 28748093
TI  - Pathological features of explant lungs with fibrosis in autoimmune pulmonary
      alveolar proteinosis.
AB  - Association of fibrosis with autoimmune pulmonary alveolar proteinosis (aPAP) is
      rare. However, prognoses of such cases are poor and the process of the formation
      of fibrosis is still unknown. In this study, we report a case of aPAP with
      progressive fibrosis occurring in a 46-year-old woman. She had undergone several
      repetitions of whole lung lavage (WLL) for 7 years and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) inhalation for 3 months; however, the
      progression of fibrosis was not hindered. Eventually, she was treated with
      bilateral lung transplantation. The computed tomography (CT) image suggested
      pulmonary fibrotic changes in her lung similar to usual interstitial pneumonia.
      However, the pathological analyses of explant lungs revealed that the fibrosis
      was not similar to ordinary interstitial pneumonias and suggested that the
      dysfunction of alveolar macrophage in removing the excess surfactant of alveolar
      spaces played an important role in the fibrogenesis in aPAP.

PMID- 28748094
TI  - Metastatic squamous cell carcinoma of the lung mimicking multiple bone abscesses.
AB  - Squamous cell carcinoma of the lung is known to metastasize to the bones, but a
      presentation similar to bone abscess is rare. We encountered a case with bone
      metastases that mimicked bone abscess, which delayed the diagnosis of squamous
      cell lung carcinoma. A 67-year-old man presented with a left upper lung
      infiltrate and lytic lesions on the left first rib and right fifth rib. In
      consideration of a possible infectious process, cultures of the aspirate from the
      right fifth rib lesion and blood were taken; however, results were non-specific.
      Thereafter, bronchoscopic biopsy of the left upper lung nodule and ultrasound
      guided biopsy of the right fifth rib lesion yielded a diagnosis of squamous cell
      lung carcinoma with bone metastases. Metastatic squamous cell lung carcinoma may
      have imaging characteristics of bone abscess and should be considered in the
      differential diagnosis of such lesions.

PMID- 28748095
TI  - The Origin of Mathematics and Number Sense in the Cerebellum: with Implications
      for Finger Counting and Dyscalculia.
AB  - BACKGROUND: Mathematicians and scientists have struggled to adequately describe
      the ultimate foundations of mathematics. Nobel laureates Albert Einstein and
      Eugene Wigner were perplexed by this issue, with Wigner concluding that the
      workability of mathematics in the real world is a mystery we cannot explain. In
      response to this classic enigma, the major purpose of this article is to provide
      a theoretical model of the ultimate origin of mathematics and "number sense" (as
      defined by S. Dehaene) that is proposed to involve the learning of inverse
      dynamics models through the collaboration of the cerebellum and the cerebral
      cortex (but prominently cerebellum-driven). This model is based upon (1) the
      modern definition of mathematics as the "science of patterns," (2) cerebellar
      sequence (pattern) detection, and (3) findings that the manipulation of numbers
      is automated in the cerebellum. This cerebro-cerebellar approach does not
      necessarily conflict with mathematics or number sense models that focus on brain
      functions associated with especially the intraparietal sulcus region of the
      cerebral cortex. A direct corollary purpose of this article is to offer a
      cerebellar inner speech explanation for difficulty in developing "number sense"
      in developmental dyscalculia. RESULTS: It is argued that during infancy the
      cerebellum learns (1) a first tier of internal models for a primitive physics
      that constitutes the foundations of visual-spatial working memory, and (2) a
      second (and more abstract) tier of internal models based on (1) that learns
      "number" and relationships among dimensions across the primitive physics of the
      first tier. Within this context it is further argued that difficulty in the early
      development of the second tier of abstraction (and "number sense") is based on
      the more demanding attentional requirements imposed on cerebellar inner speech
      executive control during the learning of cerebellar inverse dynamics models.
      Finally, it is argued that finger counting improves (does not originate) "number
      sense" by extending focus of attention in executive control of silent cerebellar
      inner speech. DISCUSSION: It is suggested that (1) the origin of mathematics has
      historically been an enigma only because it is learned below the level of
      conscious awareness in cerebellar internal models, (2) understandings of the
      development of "number sense" and developmental dyscalculia can be advanced by
      first understanding the ultimate foundations of number and mathematics do not
      simply originate in the cerebral cortex, but rather in cerebro-cerebellar
      collaboration (predominately driven by the cerebellum). CONCLUSION: It is
      concluded that difficulty with "number sense" results from the extended demands
      on executive control in learning inverse dynamics models associated with
      cerebellar inner speech related to the second tier of abstraction (numbers) of
      the infant's primitive physics.

PMID- 28748096
TI  - Unemployment and HIV mortality in the countries of the Organisation for Economic
      Co-operation and Development: 1981-2009.
AB  - OBJECTIVES: To determine an association between unemployment rates and human
      immunodeficiency virus (HIV) mortality in the Organisation for Economic Co
      operation and Development (OECD). DESIGN: Multivariate regression analysis.
      PARTICIPANTS: OECD member states. SETTING: OECD. MAIN OUTCOME MEASURES: World
      Health Organization HIV mortality. RESULTS: Between 1981 and 2009, a 1% increase
      in unemployment was associated with an increase in HIV mortality in the OECD
      (coefficient for men 0.711, 0.334-1.089, p = 0.0003; coefficient for women 0.166,
      0.071-0.260, p = 0.0007). Time lag analysis showed a significant increase in HIV
      mortality for up to two years after rises in unemployment: p = 0.0008 for men and
      p = 0.0030 for women in year 1, p = 0.0067 for men and p = 0.0403 for women in
      year 2. CONCLUSIONS: Rises in unemployment are associated with increased HIV
      mortality. Economic fiscal policy may impact upon population health. Policy
      discussions should take into consideration potential health outcomes.

PMID- 28748097
TI  - Multiple organ dysfunction due to heatstroke after sauna: case report and review
      of the literature.
AB  - Heatstroke usually occurs in summer during heat waves, and few cases occur in
      winter. We report the case of a 26-year-old man who went through multiple organ
      dysfunction after sauna in January, and finally was diagnosed as heatstroke.

PMID- 28748098
TI  - A remote metastatic giant cell tumour to the skull.
AB  - This case discusses an unusual presentation of remote metastatic giant cell
      tumour presenting as a seizure.

PMID- 28748099
TI  - A rare case of a medullary, multifocal lesion in the distal radius.
AB  - In multifocal findings, the possibility of multifocal osteoid osteomas should be
      considered and this case helps us to be attentive for the unusual radiographical
      presentation of osteoid osteoma.

PMID- 28748100
TI  - A case of hypercalcaemia in an immunocompetent patient with Mycobacterium avium
      intracellulare.
AB  - Mycobacterium avium intracellulare infection or colonization should be considered
      in the differential diagnosis of hypercalcemia, especially in immunocompromised
      individuals, in the appropriate clinical context.

PMID- 28748101
TI  - Evaluation of a Hockey Deceased Organ Donation Awareness Campaign: A Population
      Based Cohort Study.
AB  - BACKGROUND: The Kidney Foundation of Canada developed a pilot campaign to educate
      persons attending junior hockey league games in London, Ontario, Canada, on
      deceased organ donation. OBJECTIVE: To evaluate the impact of a hockey campaign
      on the number of new organ and tissue donor registrants. DESIGN: Population-based
      retrospective cohort study. SETTING: Residents of London, Ontario. PATIENTS: We
      included 255 476 individuals eligible to register for organ donation with a
      London, Ontario postal code. MEASUREMENTS: We compared the number of new deceased
      organ donor registrants in London, Ontario, during the campaign period (March 12
      to April 16, 2015) with 3 different time periods (December 30, 2014 to February
      3, 2015; February 4 to March 11, 2015; April 17 to May 22, 2015). We also
      compared registration rates in London with 2 Ontario cities (Kitchener-Waterloo
      and Hamilton) matching in a 1:1 ratio on age, sex, and income quintile. METHODS:
      To compare registrations across time periods, we used binomial regression with an
      identity link function and generalized estimating equations with an independence
      correlation structure. We used modified Poisson regression to compare
      registration rates between cities. RESULTS: During the campaign period, there
      were slightly more registrations (1218 registered of 252 832 unregistered
      individuals [0.48%]) compared with an earlier time period (risk difference:
      0.09%; 95% confidence interval [CI]: 0.05%-0.12%). However, there was no
      significant difference compared with 2 time periods immediately before and after
      the campaign. London had slightly more registrations during the campaign period
      compared with the matched city of Hamilton (1180 registered of 236 582
      unregistered individuals [0.50%] vs 490 registered of 236 582 unregistered
      individuals [0.21%]; risk ratio: 2.41; 95% CI: 2.17-2.68). The registration rate
      in London did not significantly differ from Kitchener-Waterloo. LIMITATIONS:
      Unable to conclude whether the minor increase in deceased organ donor
      registration was the result of the campaign or other factors (e.g., simultaneous
      organ registration events, seasonality). CONCLUSIONS: Overall, a minor increase
      in deceased organ donor registration was observed during the hockey organ
      donation awareness campaign; however, the specific impact of the campaign on
      organ donor registration could not be determined.

PMID- 28748102
TI  - Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced
      neurite retraction in PC12 cells.
AB  - BACKGROUND: In chemotherapy, the full round of treatment must be completed as
      scheduled to achieve the strongest therapeutic effect. However, peripheral
      neuropathy, a severe side effect of the chemotherapeutic agent paclitaxel, can
      force the premature discontinuation of treatment. As some kampo practitioners
      have suggested that it may be possible to counteract such side effects, we
      analyzed the effects of Kamishoyosan, Shakuyakukanzoto, and Goshajinkigan in an
      in vitro model of paclitaxel-induced peripheral neuropathy. METHODS: Paclitaxel
      treated PC12 cells were assessed for neurite length and performed Western blot
      analysis for growth-associated protein-43 (GAP-43) and light neurofilament
      protein (NF-L) levels in the presence of nerve growth factor (NGF); they were re
      assessed, with additional testing for acetylcholinesterase levels, after
      application of one of the kampo. We also compared phosphorylation of
      extracellular signal-regulated kinase (Erk)1/2 and Akt via Western blot analysis.
      About effect of kampo to anticancer efficacy, we confirmed cell cytotoxicity in
      A549 cells using MTT assay. RESULTS: Addition of Kamishoyosan or
      Shakuyakukanzoto, but not Goshajinkigan, significantly improved neurite length
      and GAP-43 and NF-L levels from paclitaxel-treated PC12 cells, relative to those
      of only NGF-treated PC12 cells. The promoting effect of Kamishoyosan and
      Shakuyakukanzoto in neurite outgrowth is confirmed when NGF promoted neurite
      outgrowth, and it was inhibited partially when Erk1/2 and Akt were blocked by
      Erk1/2 inhibitor or Akt inhibitor alone. Furthermore, neurite outgrowth induced
      by TJ24 and TJ68 was inhibited more strongly when Erk1/2 inhibitor and Akt
      inhibitor were treated at the same time. NGF with Kamishoyosan or
      Shakuyakukanzoto promoted the proportion of phosphorylated Erk1/2 and
      phosphorylated Akt compare with NGF only. On the other hand, Kamishoyosan or
      Shakuyakukanzoto didn't influence cytotoxicity of paclitaxel in A549 cells.
      CONCLUSIONS: Kamishoyosan or Shakuyakukanzoto promotes neurite outgrowth with NGF
      via increasing the proportion of phosphorylated Erk1/2 and phosphorylated Akt in
      PC12 cells. The effect applies to recovery from paclitaxel-induced axonal
      involvement and might promote recovery from paclitaxel-induced neuropathy without
      influence of anticancer effect of paclitaxel.

PMID- 28748103
TI  - Role of ghrelin in the pancreatic exocrine secretion via mitogen-activated
      protein kinase signaling in rats.
AB  - BACKGROUND: This study was performed to investigate the impact of exogenous
      ghrelin on the pancreatic alpha-amylase outputs and responses of pancreatic
      proteins to ghrelin that may relate to pancreatic exocrine. METHODS: Sprague
      Dawley male rats (9 weeks old, 300 +/- 10 g) were injected with ghrelin via
      intraperitoneal (i.p.) infusion at dosage of 0, 0.1, 1.0 and 10.0 MUg/kg body
      weight (BW), respectively. The plasma ghrelin and cholecystokinin (CCK) level
      were determined using enzyme immunoassay kit; the mRNA expression of ghrelin
      receptor (GHSR-1alpha) and growth hormone (GH) receptor were assessed by reverse
      transcription PCR; the expressions of pancreatic alpha-amylase activity,
      extracellular-signal-regulated kinases (ERK), phosphorylated extracellular-signal
      regulated kinases (pERK) and c-Jun N-terminal kinase (JNK) were evaluated by
      western blotting; moreover the responses of pancreatic proteins to ghrelin were
      analyzed using the two-dimensional gel electrophoresis system. RESULTS: The
      exogenous ghrelin (1.0 and 10.0 MUg/kg BW) elevated the level of plasma ghrelin
      (p < 0.05), and suppressed the expression of pancreatic alpha-amylase at a dose
      of 10.0 MUg/kg BW (p < 0.05). No difference in the level of plasma CCK was
      observed, even though rats were exposed to any dose of exogenous ghrelin. In
      addition, a combination of western blot and proteomic analysis revealed exogenous
      ghrelin (10.0 MUg/kg BW) induced increasing the JNK and ERK expressions (p <
      0.05) and four proteins such as Destrin, Anionic trypsin-1, Trypsinogen, and
      especially eukaryotic translation initiation factor 3 in rat pancreas.
      CONCLUSIONS: Taken together, exogenous ghrelin by i.p. infusion plays a role in
      the pancreatic exocrine secretion via mitogen-activated protein kinase signaling
      pathway.

PMID- 28748104
TI  - Stress at work: Factors associated with cognitive disorganisation among private
      sector professionals.
AB  - This study explores psychological and psychological variables associated with
      perceived stress at work. A total of 100 international participants consented to
      donating a hair sample and completing a work-related stress survey. Logistic
      regression was used to investigate associations with low/high cognitive
      disorganisation using data collected from hair cortisol analysis and self-report
      questionnaires. High cognitive disorganisation scores were associated with high
      cardiopulmonary and anger scores. Low perceived self-efficacy was associated with
      high cognitive disorganisation. An association was found between low cortisol and
      low perceived self-efficacy. The relationship between high cognitive
      disorganisation and low self-efficacy endorses previous claims linking
      performance to perceived high self-efficacy.

PMID- 28748105
TI  - A feasibility study of the Mini-AFTER telephone intervention for the management
      of fear of recurrence in breast cancer survivors: a mixed-methods study protocol.
AB  - BACKGROUND: Fear of recurrence (FoR) is a major concern for patients following
      treatment for primary breast cancer, affecting 60-99% of breast cancer survivors.
      Mini-AFTER is a brief intervention developed to address this fear, that breast
      care nurses are ideally placed to deliver. However, their interest in delivering
      such an intervention is unknown and crucial to its introduction. This study aims
      to assess the perceived feasibility of the Mini-AFTER telephone intervention for
      implementation by breast care nurses to manage moderate levels of fear of
      recurrence among breast cancer survivors. METHODS: A sequential explanatory mixed
      methods design will be used, informed by normalisation process theory (NPT). The
      design will be guided by the stages of NPT. Specifically, understanding and
      evaluating the process (implementation) that would enable an intervention, such
      as the Mini-AFTER, not only to be operationalised and normalised into everyday
      work (embedded) but also sustained in practice (integration). Phase 1: all
      members on the UK Breast Cancer Care Nursing Network database (n = 905) will be
      emailed a link to a web-based survey, designed to investigate how breast cancer
      survivors' FoR is identified and managed within current services and their
      willingness to deliver the Mini-AFTER. Phase 2: a purposive sample of respondents
      (n = 20) will be interviewed to build upon the responses in phase 1 and explore
      breast care nurses' individual views on the importance of addressing fear of
      recurrence in their clinical consultations, interest in the Mini-AFTER
      intervention, the content, skills required and challenges to deliver the
      intervention. DISCUSSION: This study will provide information about the
      willingness of breast care nurses (BCNs) to provide a structured intervention to
      manage fear of recurrence. It will identify barriers and facilitators for
      effective delivery and inform the future design of a larger trial of the Mini
      AFTER intervention.

PMID- 28748106
TI  - A feasibility study of a theory-based intervention to improve appropriate
      polypharmacy for older people in primary care.
AB  - BACKGROUND: A general practitioner (GP)-targeted intervention aimed at improving
      the prescribing of appropriate polypharmacy for older people was previously
      developed using a systematic, theory-based approach based on the UK Medical
      Research Council's complex intervention framework. The primary intervention
      component comprised a video demonstration of a GP prescribing appropriate
      polypharmacy during a consultation with an older patient. The video was delivered
      to GPs online and included feedback emphasising the positive outcomes of
      performing the behaviour. As a complementary intervention component, patients
      were invited to scheduled medication review consultations with GPs. This study
      aimed to test the feasibility of the intervention and study procedures
      (recruitment, data collection). METHODS: GPs from two general practices were
      given access to the video, and reception staff scheduled consultations with older
      patients receiving polypharmacy (>=4 medicines). Primary feasibility study
      outcomes were the usability and acceptability of the intervention to GPs.
      Feedback was collected from GP and patient participants using structured
      questionnaires. Clinical data were also extracted from recruited patients'
      medical records (baseline and 1 month post-consultation). The feasibility of
      applying validated assessment of prescribing appropriateness (STOPP/START
      criteria, Medication Appropriateness Index) and medication regimen complexity
      (Medication Regimen Complexity Index) to these data was investigated. Data
      analysis was descriptive, providing an overview of participants' feedback and
      clinical assessment findings. RESULTS: Four GPs and ten patients were recruited
      across two practices. The intervention was considered usable and acceptable by
      GPs. Some reservations were expressed by GPs as to whether the video truly
      reflected resource and time pressures encountered in the general practice working
      environment. Patient feedback on the scheduled consultations was positive.
      Patients welcomed the opportunity to have their medications reviewed. Due to the
      short time to follow-up and a lack of detailed clinical information in patient
      records, it was not feasible to detect any prescribing changes or to apply the
      assessment tools to patients' clinical data. CONCLUSION: The findings will help
      to further refine the intervention and study procedures (including time to follow
      up) which will be tested in a randomised pilot study that will inform the design
      of a definitive trial to evaluate the intervention's effectiveness. TRIAL
      REGISTRATION: ISRCTN18176245.

PMID- 28748107
TI  - Study protocol: a mixed methods feasibility study for a loaded self-managed
      exercise programme for patellofemoral pain.
AB  - BACKGROUND: Patellofemoral pain (PFP) is one of the most common forms of knee
      pain in adults under the age of 40, with a prevalence of 23% in the general
      population. The long-term prognosis is poor, with only one third of people pain
      free 1 year after diagnosis. The biomedical model of pain in relation to
      persistent PFP has recently been called into question. It has been suggested that
      interventions for chronic musculoskeletal conditions should consider alternative
      mechanisms of action, beyond muscles and joints. Modern treatment therapies
      should consider desensitising strategies, with exercises that target movements
      and activities patients find fearful and painful. High-quality research on
      exercise prescription in relation to pain mechanisms, not directed at specific
      tissue pathology, and dose response clearly warrants further investigation. Our
      primary aim is to establish the feasibility and acceptability of conducting a
      definitive RCT which will evaluate the clinical and cost-effectiveness of a
      loaded self-managed exercise programme for people with patellofemoral pain.
      METHOD: This is a single-centred, multiphase, sequential, mixed-methods trial
      that will evaluate the feasibility of running a definitive large-scale randomised
      controlled trial of a loaded self-managed exercise programme versus usual
      physiotherapy. Initially, 8-10 participants with a minimum 3-month history of PFP
      will be recruited from an NHS physiotherapy waiting list and interviewed.
      Participants will be invited to discuss perceived barriers and facilitators to
      exercise engagement, and the meaning and impact of PFP. Then, 60 participants
      will be recruited in the same manner for the main phase of the feasibility trial.
      A web-based service will randomise patients to a loaded self-managed exercise
      programme or usual physiotherapy. The loaded self-managed exercise programme is
      aimed at addressing lower limb knee and hip weakness and is positioned within a
      framework of reducing fear/avoidance with an emphasis on self-management.
      Baseline assessment will include demographic data, average pain within the last
      week (VAS), fear avoidance behaviours, catastrophising, self-efficacy, sport and
      leisure activity participation, and general quality of life. Follow-up will be 3
      and 6 months. The analysis will focus on descriptive statistics and confidence
      intervals. The qualitative components will follow a thematic analysis approach.
      DISCUSSION: This study will evaluate the feasibility of running a definitive
      large-scale trial on patients with patellofemoral pain, within the NHS in the UK.
      We will identify strengths and weaknesses of the proposed protocol and the
      utility and characteristics of the outcome measures. The results from this study
      will inform the design of a multicentre trial. TRIAL REGISTRATION:
      ISRCTN35272486.

PMID- 28748108
TI  - ReaDySpeech for people with dysarthria after stroke: protocol for a feasibility
      randomised controlled trial.
AB  - BACKGROUND: Dysarthria, a disordered speech production resulting from neuro
      muscular impairment, is a common symptom after stroke. It causes significant
      problems for patients' speech intelligibility, communication, psychological well
      being, social engagement and stroke recovery. Rehabilitation for dysarthria is
      variable in quality, intensity and duration, which may be, in part, due to the
      lack of good quality evidence. An online therapy programme, ReaDySpeech, has the
      potential to improve quality, intensity and duration of speech rehabilitation and
      was considered in a proof-of-concept study to be acceptable to speech and
      language therapists and patients which warranted further evaluation. The present
      study aims to examine the feasibility of running a trial using the ReaDySpeech
      intervention. METHODS/DESIGN: A feasibility, randomised controlled trial, will
      recruit a minimum of 36 people with post-stroke dysarthria who are more than 1
      week post stroke. Participants will be externally randomised in a 2:1 ratio to
      receive either ReaDySpeech and usual care (24 participants) or usual care only
      (12 participants). This study is single blind with the researcher carrying out
      the baseline and outcome measures while blinded to treatment allocation. The
      primary objective is to assess the feasibility of conducting a larger Phase III
      trial. The specific objectives are to determine the following: recruitment rate
      and reasons for non-recruitment; loss of participants to follow-up; acceptability
      of randomisation; adherence to the intervention; delivery of ReaDySpeech and
      content; acceptability of outcome measures; success of blinding strategies;
      defining 'usual' care; and the implications of the intervention for the
      patient/family/carer. DISCUSSION: This study will involve a regional, multi
      centre, randomised controlled feasibility trial of a complex intervention in
      order to evaluate whether a Phase III randomised controlled trial is feasible.
      TRIAL REGISTRATION: Current Controlled Trials, ISRCTN84996500.

PMID- 28748109
TI  - Un-explained visual loss following silicone oil removal: results of the Pan
      American Collaborative Retina Study (PACORES) Group.
AB  - PURPOSE: To report the incidence and clinical features of patients that
      experienced un-explained visual loss following silicone oil (SO) removal.
      METHODS: Multicenter retrospective study of patients that underwent SO removal
      during 2000-2012. Visual loss of >=2 lines was considered significant. RESULTS: A
      total of 324 eyes of 324 patients underwent SO removal during the study period.
      Forty two (13%) eyes suffered a significant visual loss following SO removal.
      Twenty three (7.1%) of these eyes lost vision secondary to known causes. In the
      remaining 19 (5.9%) eyes, the loss of vision was not explained by any other
      pathology. Eleven of these 19 patients (57.9%) were male. The mean age of this
      group was 49.2 +/- 16.4 years. Eyes that had an un-explained visual loss had a
      mean IOP while the eye was filled with SO of 19.6 +/- 6.9 mm Hg. The length of
      time that the eye was filled with SO was 14.8 +/- 4.4 months. In comparison, eyes
      that did not experience visual loss had a mean IOP of 14 +/- 7.3 mm Hg (p <
      0.0002) and a mean tamponade duration of 9.3 +/- 10.9 months (p < 0.0001).
      CONCLUSIONS: An un-explained visual loss after SO removal was observed in 5.9% of
      eyes. Factors associated with this phenomenon included a higher IOP and longer SO
      tamponade duration.

PMID- 28748110
TI  - Unbiased whole-genome deep sequencing of human and porcine stool samples reveals
      circulation of multiple groups of rotaviruses and a putative zoonotic infection.
AB  - Coordinated and synchronous surveillance for zoonotic viruses in both human
      clinical cases and animal reservoirs provides an opportunity to identify
      interspecies virus movement. Rotavirus (RV) is an important cause of viral
      gastroenteritis in humans and animals. In this study, we document the RV
      diversity within co-located humans and animals sampled from the Mekong delta
      region of Vietnam using a primer-independent, agnostic, deep sequencing approach.
      A total of 296 stool samples (146 from diarrhoeal human patients and 150 from
      pigs living in the same geographical region) were directly sequenced, generating
      the genomic sequences of sixty human rotaviruses (all group A) and thirty-one
      porcine rotaviruses (thirteen group A, seven group B, six group C, and five group
      H). Phylogenetic analyses showed the co-circulation of multiple distinct RV group
      A (RVA) genotypes/strains, many of which were divergent from the strain
      components of licensed RVA vaccines, as well as considerable virus diversity in
      pigs including full genomes of rotaviruses in groups B, C, and H, none of which
      have been previously reported in Vietnam. Furthermore, the detection of an
      atypical RVA genotype constellation (G4-P[6]-I1-R1-C1-M1-A8-N1-T7-E1-H1) in a
      human patient and a pig from the same region provides some evidence for a
      zoonotic event.

PMID- 28748111
TI  - Dimerized Domain V of Beta2-Glycoprotein I Is Sufficient to Upregulate
      Procoagulant Activity in PMA-Treated U937 Monocytes and Require Intact Residues
      in Two Phospholipid-Binding Loops.
AB  - Upregulation of the procoagulant activity of monocytes by antibodies to beta2-
      glycoprotein I (beta2GPI) is one of the mechanisms contributing to thrombosis in
      antiphospholipid syndrome. Current knowledge about receptors responsible for the
      upregulation of procoagulant activity by beta2GPI/anti-beta2GPI complexes and
      their binding sites on beta2GPI is far from complete. We quantified the
      procoagulant activity expressed by phorbol 12-myristate 13-acetate (PMA)-
      differentiated U937 cells by measuring clotting kinetics in human plasma exposed
      to stimulated cells. Cells stimulated with anti-beta2GPI were compared to cells
      treated with dimerized domain V of beta2GPI (beta2GPI-DV) or point mutants of
      beta2GPI-DV. We demonstrated that dimerized beta2GPI-DV is sufficient to induce
      procoagulant activity in monocytes. Using site-directed mutagenesis, we
      determined that the phospholipid-binding interface on beta2GPI is larger than
      previously thought and includes Lys308 in beta2GPI-DV. Intact residues in two
      phospholipid-binding loops of beta2GPI-DV were important for the potentiation of
      procoagulant activity. We did not detect a correlation between the ability of
      beta2GPI-DV variants to bind ApoER2 and potentiation of the procoagulant activity
      of cells. The region on beta2GPI inducing procoagulant activity in monocytes can
      now be narrowed down to beta2GPI-DV. The ability of beta2GPI-DV dimers to come
      close to cell membrane and attach to it is important for the stimulation of
      procoagulant activity.

PMID- 28748112
TI  - Visually Lossless JPEG 2000 for Remote Image Browsing.
AB  - Image sizes have increased exponentially in recent years. The resulting high
      resolution images are often viewed via remote image browsing. Zooming and panning
      are desirable features in this context, which result in disparate spatial regions
      of an image being displayed at a variety of (spatial) resolutions. When an image
      is displayed at a reduced resolution, the quantization step sizes needed for
      visually lossless quality generally increase. This paper investigates the
      quantization step sizes needed for visually lossless display as a function of
      resolution, and proposes a method that effectively incorporates the resulting
      (multiple) quantization step sizes into a single JPEG2000 codestream. This
      codestream is JPEG2000 Part 1 compliant and allows for visually lossless decoding
      at all resolutions natively supported by the wavelet transform as well as
      arbitrary intermediate resolutions, using only a fraction of the full-resolution
      codestream. When images are browsed remotely using the JPEG2000 Interactive
      Protocol (JPIP), the required bandwidth is significantly reduced, as demonstrated
      by extensive experimental results.

PMID- 28748113
TI  - Uric acid and life on earth.

PMID- 28748114
TI  - Uric acid in plants and microorganisms: Biological applications and genetics - A
      review.
AB  - Uric acid increased accumulation and/or reduced excretion in human bodies is
      closely related to pathogenesis of gout and hyperuricemia. It is highly affected
      by the high intake of food rich in purine. Uric acid is present in both higher
      plants and microorganisms with species dependent concentration. Urate-degrading
      enzymes are found both in plants and microorganisms but the mechanisms by which
      plant degrade uric acid was found to be different among them. Higher plants
      produce various metabolites which could inhibit xanthine oxidase and xanthine
      oxidoreductase, so prohibit the oxidation of hypoxanthine to xanthine then to
      uric acid in the purine metabolism. However, microorganisms produce group of
      degrading enzymes uricase, allantoinase, allantoicase and urease, which catalyze
      the degradation of uric acid to the ammonia. In humans, researchers found that
      several mutations caused a pseudogenization (silencing) of the uricase gene in
      ancestral apes which exist as an insoluble crystalloid in peroxisomes. This is in
      contrast to microorganisms in which uricases are soluble and exist either in
      cytoplasm or peroxisomes. Moreover, many recombinant uricases with higher
      activity than the wild type uricases could be induced successfully in many
      microorganisms. The present review deals with the occurrence of uric acid in
      plants and other organisms specially microorganisms in addition to the mechanisms
      by which plant extracts, metabolites and enzymes could reduce uric acid in blood.
      The genetic and genes encoding for uric acid in plants and microorganisms are
      also presented.

PMID- 28748115
TI  - Physiological functions and pathogenic potential of uric acid: A review.
AB  - Uric acid is synthesized mainly in the liver, intestines and the vascular
      endothelium as the end product of an exogenous pool of purines, and endogenously
      from damaged, dying and dead cells, whereby nucleic acids, adenine and guanine,
      are degraded into uric acid. Mentioning uric acid generates dread because it is
      the established etiological agent of the severe, acute and chronic inflammatory
      arthritis, gout and is implicated in the initiation and progress of the metabolic
      syndrome. Yet, uric acid is the predominant anti-oxidant molecule in plasma and
      is necessary and sufficient for induction of type 2 immune responses. These
      properties may explain its protective potential in neurological and infectious
      diseases, mainly schistosomiasis. The pivotal protective potential of uric acid
      against blood-borne pathogens and neurological and autoimmune diseases is yet to
      be established.

PMID- 28748116
TI  - Gout: An old disease in new perspective - A review.
AB  - Gout is a picturesque presentation of uric acid disturbance. It is the most well
      understood and described type of arthritis. Its epidemiology is studied. New
      insights into the pathophysiology of hyperuricemia and gouty arthritis; acute and
      chronic allow for an even better understanding of the disease. The role of
      genetic predisposition is becoming more evident. The clinical picture of gout is
      divided into asymptomatic hyperuricemia, acute gouty arthritis, intercritical
      period, and chronic tophaceous gout. Diagnosis is based on laboratory and
      radiological features. The gold standard of diagnosis is identification of
      characteristic MSU crystals in the synovial fluid using polarized light
      microscopy. Imaging modalities include conventional radiography, ultrasonography,
      conventional CT, Dual-Energy CT, Magnetic Resonance Imaging, nuclear
      scintigraphy, and positron emission tomography. There is remarkable progress in
      the application of ultrasonography and Dual-Energy CT which is bound to influence
      the diagnosis, staging, follow-up, and clinical research in the field. Management
      of gout includes management of flares, chronic gout and prevention of flares, as
      well as management of comorbidities. Newer drugs in the pharmacological
      armamentarium are proving successful and supplement older ones. Other important
      points in its management include patient education, diet and life style changes,
      as well as cessation of hyperuricemic drugs.

PMID- 28748117
TI  - Epidemiology, pathophysiology, and management of uric acid urolithiasis: A
      narrative review.
AB  - An in-depth comprehension of the epidemiology as well as pathophysiology of uric
      acid urolithiasis is important for the identification, treatment, and prophylaxis
      of calculi in these patients. Persistently low urinary pH, hyperuricosuria, and
      low urinary volume are the most important factors in pathogenesis of uric acid
      urolithiasis. Other various causes of calculus formation comprises of chronic
      diarrhea, renal hyperuricosuria, insulin resistance, primary gout, extra purine
      in the diet, neoplastic syndromes, and congenital hyperuricemia. Non-contrast
      enhanced computed tomography is the radiologic modality of choice for early
      assessment of patients with renal colic. Excluding situations where there is
      acute obstruction, rising blood chemistry, severe infection, or unresolved pain,
      the initial management ought to be medical dissolution by oral chemolysis since
      this method has proved to be effective in most of the cases.

PMID- 28748118
TI  - Serum uric acid and acute kidney injury: A mini review.
AB  - Acute kidney injury causes great morbidity and mortality in both the community
      and hospital settings. Understanding the etiological factors and the
      pathophysiological principles resulting in acute kidney injury is essential in
      prompting appropriate therapies. Recently hyperuricemia has been recognized as a
      potentially modifiable risk factor for acute kidney injury, including that
      associated with cardiovascular surgery, radiocontrast administration,
      rhabdomyolysis, and associated with heat stress. This review discussed the
      evidence that repeated episodes of acute kidney injury from heat stress and
      dehydration may also underlie the pathogenesis of the chronic kidney disease
      epidemic that is occurring in Central America (Mesoamerican nephropathy).
      Potential mechanisms for how uric acid might contribute to acute kidney injury
      are also discussed, including systemic effects on renal microvasculature and
      hemodynamics, and local crystalline and noncrystalline effects on the renal
      tubules. Pilot clinical trials also show potential benefits of lowering uric acid
      on acute kidney injury associated with a variety of insults. In summary, there is
      mounting evidence that hyperuricemia may have a significant role in the
      development of acute kidney injury. Prospective, placebo controlled, randomized
      trials are needed to determine the potential benefit of uric acid lowering
      therapy on kidney and cardio-metabolic diseases.

PMID- 28748120
TI  - The grey zone of Hyperuricemia in chronic kidney disease.

PMID- 28748121
TI  - Treatment of asymptomatic hyperuricemia in chronic kidney disease: A new target
      in an old enemy - A review.
AB  - Asymptomatic hyperuricemia is increasing in prevalence. There is a growing body
      of literature suggesting that uric acid has deleterious effects on vascular
      health and renal histological integrity. Several trials, reviewed herein, suggest
      that lowering the serum uric acid level is associated with a slowing in the rate
      of renal deterioration in those with chronic kidney disease. Given that there is
      little available in the general armamentarium to slow the rate of kidney
      deterioration, strong consideration could be given to the administration of
      agents or lifestyle changes that decrease uric acid production in hyperuricemic
      patients with deteriorating kidney function.

PMID- 28748119
TI  - Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: A
      review.
AB  - The association between uric acid (UA) on one side and systemic hypertension
      (Htn), dyslipidemia, glucose intolerance, overweight, fatty liver, renal disease
      and cardiovascular disease (CVD) on the other side is well recognized. However,
      the causal relationship between UA and these different clinical problems is still
      debatable. The recent years have witnessed hundreds of experimental and clinical
      trials that favored the opinion that UA is a probable player in the pathogenesis
      of these disease entities. These studies disclosed the strong association between
      hyperuricemia and metabolic syndrome (MS), obesity, Htn, type 2 diabetes mellitus
      (DM), non-alcoholic fatty liver disease, hypertriglyceridemia, acute kidney
      injury, chronic kidney disease (CKD), coronary heart disease (CHD), heart failure
      and increased mortality among cardiac and CKD patients. The association between
      UA and nephrolithiasis or preeclampsia is a non-debatable association. Recent
      experimental trials have disclosed different changes in enzyme activities induced
      by UA. Nitric oxide (NO) synthase, adenosine monophosphate kinase (AMPK),
      adenosine monophosphate dehydrogenase (AMPD), and nicotinamide adenine
      dinucleotide phosphate (NADPH)-oxidase are affected by UA. These changes in
      enzymatic activities can lead to the observed biochemical and pathological
      changes associated with UA. The recent experimental, clinical, interventional,
      and epidemiologic trials favor the concept of a causative role of UA in the
      pathogenesis of MS, renal, and CVDs.

PMID- 28748122
TI  - Asymptomatic hyperuricemia and chronic kidney disease: Narrative review of a
      treatment controversial.
AB  - Today there is plausible evidence both on experimental and epidemiological basis,
      that hyperuricemia represents a risk factor for the development and progression
      of chronic kidney disease (CKD). Nevertheless, the role of serum uric acid
      lowering treatment in CKD is still a matter of serious controversy. Review of
      randomised controlled trials, suggests that there may be an improvement of renal
      function with allopurinol treatment in CKD stage 3-5. However, these studies have
      included a relatively limited number of participants and provide insufficient
      information on adverse events and on the incidence of the end stage renal
      disease. Therefore, before adequately powered randomised, placebo-controlled
      trials are completed we cannot recommend treating asymptomatic hyperuricemia in
      patients with CKD.

PMID- 28748123
TI  - Shape affects the interactions of nanoparticles with pulmonary surfactant.
AB  - The interactions with the pulmonary surfactant, the initial biological barrier of
      respiratory pathway, determine the potential therapeutic applications and
      toxicological effects of inhaled nanoparticles (NPs). Although much attention has
      been paid to optimize the physicochemical properties of NPs for improved delivery
      and targeting, shape effects of the inhaled NPs on their interactions with the
      pulmonary surfactant are still far from clear. Here, we studied the shape effects
      of NPs on their penetration abilities and structural disruptions to the
      dipalmitoyl-phosphatidylcholine (DPPC) monolayer (being model pulmonary
      surfactant film) using coarse-grained molecular dynamics simulations. It is found
      that during the inspiration process (i.e., surfactant film expansion), shape
      effects are negligible. However, during the expiration process (i.e., surfactant
      film compression), NPs of different shapes show various penetration abilities and
      degrees of structural disruptions to the DPPC monolayer. We found that rod-like
      NPs showed the highest degree of penetration and the smallest side-effects to the
      DPPC monolayer. Our results may provide a useful insight into the design of NPs
      for respiratory therapeutics.

PMID- 28748124
TI  - Practice Makes Efficient: Cortical Alpha Oscillations Are Associated With
      Improved Golf Putting Performance.
AB  - Practice of a motor skill results in improved performance and decreased movement
      awareness. The psychomotor efficiency hypothesis proposes that the development of
      motor expertise through practice is accompanied by physiological refinements
      whereby irrelevant processes are suppressed and relevant processes are enhanced.
      The present study employed a test-retest design to evaluate the presence of
      greater neurophysiological efficiency with practice and mediation analyses to
      identify the factors accounting for performance improvements, in a golf putting
      task. Putting performance, movement-specific conscious processing,
      electroencephalographic alpha power and alpha connectivity were measured from 12
      right-handed recreational golfers (age: M = 21 years; handicap: M = 23) before
      and after 3 practice sessions. As expected, performance improved and conscious
      processing decreased with training. Mediation analyses revealed that improvements
      in performance were partly attributable to increased regional gating of alpha
      power and reduced cross-regional alpha connectivity. However, changes in
      conscious processing were not associated with performance improvements. Increased
      efficiency was manifested at the neurophysiological level as selective inhibition
      and functional isolation of task-irrelevant cortical regions (temporal regions)
      and concomitant functional activation of task-relevant regions (central regions).
      These findings provide preliminary evidence for the development of greater
      psychomotor efficiency with practice in a precision aiming task.

PMID- 28748125
TI  - Intravital imaging of a spheroid-based orthotopic model of melanoma in the mouse
      ear skin.
AB  - Multiphoton microscopy is a powerful tool that enables the visualization of
      fluorescently tagged tumor cells and their stromal interactions within tissues in
      vivo. We have developed an orthotopic model of implanting multicellular melanoma
      tumor spheroids into the dermis of the mouse ear skin without the requirement for
      invasive surgery. Here, we demonstrate the utility of this approach to observe
      the primary tumor, single cell actin dynamics, and tumor-associated vasculature.
      These methods can be broadly applied to investigate an array of biological
      questions regarding tumor cell behavior in vivo.

PMID- 28748126
TI  - Pixel-based meshfree modelling of skeletal muscles.
AB  - This paper introduces the meshfree Reproducing Kernel Particle Method (RKPM) for
      3D image-based modeling of skeletal muscles. This approach allows for
      construction of simulation model based on pixel data obtained from medical
      images. The material properties and muscle fiber direction obtained from
      Diffusion Tensor Imaging (DTI) are input at each pixel point. The reproducing
      kernel (RK) approximation allows a representation of material heterogeneity with
      smooth transition. A multiphase multichannel level set based segmentation
      framework is adopted for individual muscle segmentation using Magnetic Resonance
      Images (MRI) and DTI. The application of the proposed methods for modeling the
      human lower leg is demonstrated.

PMID- 28748127
TI  - Gender-biased regulation of human IL-17-producing cells in vitro by peptides
      corresponding to distinct HLA-DRB1 allele-coded sequences.
AB  - Susceptibility to rheumatoid arthritis (RA) is associated with HLA-DRB1 alleles
      coding a 5-amino acid sequence motif called the shared epitope (SE). To explore
      the potential mechanisms that lead to RA susceptibility, we analyze the in vitro
      effect of peptides bearing different HLA-DR4 sequences on human peripheral blood
      derived cells. Three 15-mer peptides were used: 65-79*0401 (an HLA-DRB1*04:01
      coded sequence carrying the SE motif, QKRAA); 65-79*0402 (an HLA-DRB1*04:02-coded
      sequence carrying a SE-negative motif, DERAA); 65-79*0403 (an HLA-DRB1*04:03
      coded sequence carrying a SE-negative motif, QRRAE). We found that CD4 TH17 cells
      are regulated by peptide treatment with gender bias. In male-derived T cells, all
      peptide treatments significantly reduced TH17 cell differentiation in vitro when
      compared to no peptide treatment, and to female samples. TH17 differentiation in
      samples not treated with peptides, either in the presence or absence of TH17
      polarizing cytokines, was higher in males than in females; however, in
      unfractionated PBMC after treatment with TH17 polarizing cytokines, IL-17A
      positive cells were more abundant in females than in males. In addition, SE
      positive females showed a significantly higher percentage of IL-17A-positive
      cells compared to SE-negative females. In conclusion, donor's SE status and
      gender may both influence TH17 immune polarization.

PMID- 28748129
TI  - Can vitamin K synthesis altered by dysbiosis of microbiota be blamed in the
      etiopathogenesis of venous thrombosis?

PMID- 28748128
TI  - Diagnosis of Upper-Quadrant Lymphedema Secondary to Cancer: Clinical Practice
      Guideline From the Oncology Section of APTA.
AB  - INTRODUCTION: The Oncology Section of APTA developed a clinical practice
      guideline to aid the clinician in diagnosing secondary upper-quadrant cancer
      related lymphedema. METHODS: Following a systematic review of published studies
      and a structured appraisal process, recommendations were written to guide the
      physical therapist and other health care clinicians in their diagnostic process.
      Overall, clinical practice recommendations were formulated on the basis of the
      evidence for each diagnostic method and were assigned a grade based on the
      strength of the evidence for different patient presentations and clinical
      utility. RECOMMENDATIONS: In an effort to make these clinically applicable,
      recommendations were based on the characteristics as to the location and stage of
      a patient's upper-quadrant lymphedema.

PMID- 28748130
TI  - Isolation and identification of Bifidobacterium species from feces of captive
      chimpanzees.
AB  - Recently, gut-dwelling bifidobacteria from chimpanzees, which are
      phylogenetically close to humans and have feeding habits similar to humans, have
      been frequently investigated. Given this, we speculated that like humans,
      chimpanzees would have a unique diversity of bifidobacteria. We herein describe a
      taxonomically novel member of bifidobacteria isolated from fecal samples of
      captive chimpanzees. Bifidobacteria were detected in all fecal samples by
      quantitative polymerase chain reaction. A Bifidobacterium pseudolongum-like
      species, which could not be detected using B. pseudolongum-specific primers
      targeting the groEL gene sequence, was dominant in the feces of five chimpanzees.
      Seven bifidobacterial strains were isolated from this group of five chimpanzees,
      and all isolates were identified as B. pseudolongum. B. pseudolongum has
      previously often been isolated from non-primate animals as well as humans;
      however, here we demonstrate its presence in a nonhuman primate species.

PMID- 28748131
TI  - An in vitro investigation of immunomodulatory properties of Lactobacillus
      plantarum and L. delbrueckii cells and their extracellular polysaccharides.
AB  - Many probiotic lactobacilli and their extracellular polysaccharides (EPS) have
      beneficial immunological properties. However, it is unclear how they elicit the
      host immune response. We thus investigated the immunological properties of UV
      killed Lactobacillus delbrueckii TU-1 and L. plantarum KM-9 cells as well as
      their extracellular polysaccharides (EPSs). High-performance liquid
      chromatography and ion exchange chromatography analyses showed that their EPSs
      differ in sugar composition and sugar fractionation. The immunological properties
      were evaluated in a semi-intestinal model using a Transwell co-culture system
      that employed human intestinal epithelial (Caco-2) cells on the apical side and
      murine macrophage (RAW264.7) cells on the basolateral side. The UV-killed cells
      and EPSs were added to the apical side to allow direct contact with Caco-2 cells
      and incubated for 6 hr. After incubation, the amounts of tumor necrosis factor
      alpha and several cytokines released by RAW264.7 or Caco-2 cells were quantified
      by cytotoxic activity on L929 cells (murine fibrosarcoma cell line) and
      quantitative reverse-transcriptase PCR. We found that the UV-killed cells and
      their EPSs had immunological effects on RAW264.7 cells via Caco-2 cells. The
      RAW264.7 cells showed different cytokine production profiles when treated with UV
      killed cells and EPSs. The UV-killed cells and EPSs promoted a Th1-type cellular
      response. Furthermore, we found that the UV-killed cells sent positive signals
      through Toll-like receptor (TLR) 2. Meanwhile, neither EPS sent a positive signal
      through TLR4 and TLR2. This evidence suggests that both UV-killed cells of the
      lactobacillus strains and their EPSs trigger a Th1-type immune response in a
      human host, with the former triggering the response via the TLRs expressed on its
      epithelium and the latter employing a mechanism yet to be determined, possibly
      involving a novel receptor that is designed to recognize specific patterns of
      repeating sugar in the EPSs.

PMID- 28748132
TI  - Effects of intake of Lactobacillus casei subsp. casei 327 on skin conditions: a
      randomized, double-blind, placebo-controlled, parallel-group study in women.
AB  - Lactic acid bacteria are gut flora that play key roles in intestinal homeostasis,
      which may affect a variety of physiological functions. Our preliminary double
      blind, placebo-controlled, parallel-group trials have suggested that intake of
      heat-killed Lactobacillus casei subsp. casei 327 (designated L. K-1) is effective
      for improving skin conditions. The aim of this study was to confirm the effect of
      L. K-1 intake in a randomized, double-blind, placebo-controlled, parallel-group
      study in healthy female volunteers. Sixty-four subjects were allocated to either
      the placebo food group (group P, n=32) or active food group (group A, n=32), in
      which subjects consumed lactobacillus K-1 50 mg (approximately 1 * 1011 bacteria)
      daily for 8 weeks. After excluding subjects who declined to participate (n=1),
      violated restrictions (n=4), or were judged ineligible by the principal
      investigators (n=1), data obtained with 58 subjects (30 in group A and 28 in
      group P) were analyzed for efficacy by comparing differences from pretrial levels
      between the two groups. When the level of transepidermal water loss (TEWL) was
      measured at the arm, the level of TEWL at week 4 of the intake period was
      significantly lower in group A than group P (p=0.021), suggesting an improvement
      of skin barrier function. Analysis of skin condition questionnaire data revealed
      a significant reduction in skin flakiness on the face (week 4). No adverse events
      were associated with intake of the test foods. The safety of L. K-1 was also
      confirmed in an independent open-label trial in 11 healthy subjects who consumed
      excessive amounts of L. K-1 250 mg (approximately 5 * 1011 bacteria). Intake of
      L. K-1 may therefore be beneficial to skin condition improvement.

PMID- 28748133
TI  - Anti-stress effect of the Lactobacillus pentosus strain S-PT84 in mice.
AB  - We investigated if the orally administered Lactobacillus pentosus strain S-PT84
      (S-PT84) might show anti-stress activity and ameliorate stress-induced immune
      suppression in mice. Stress of mice induced an increase in serum corticosterone
      and a decrease in splenic natural killer activity and in the number of
      splenocytes versus control mice. However, these changes were not observed in
      stressed mice that had been administered S-PT84. Furthermore, interleukin (IL)-12
      and IL-10 production, which was downregulated in lipopolysaccharide-activated
      macrophages from stressed mice, was maintained at control levels in the
      macrophages of stressed mice that had been fed S-PT84. Interferon-gamma
      production, which was downregulated in concanavalin A-activated splenocytes from
      stressed mice, tended to be maintained at control levels in stressed mice that
      had been fed S-PT84, although IL-4 production by these cells was not influenced
      by S-PT84 administration. Additionally, reduced glutathione (GSH) levels were
      decreased in serum and peritoneal macrophages from stressed mice versus controls,
      but these GSH levels were significantly higher in stressed animals that had been
      administered S-PT84 compared with those that had not. These results suggest that
      S-PT84 exerts anti-stress activity through immune modulation and/or antioxidative
      activity.

PMID- 28748134
TI  - Genomic characterization reconfirms the taxonomic status of Lactobacillus
      parakefiri.
AB  - Whole-genome sequencing was performed for Lactobacillus parakefiri JCM 8573T to
      confirm its hitherto controversial taxonomic position. Here, we report its first
      reliable reference genome. Genome-wide metrics, such as average nucleotide
      identity and digital DNA-DNA hybridization, and phylogenomic analysis based on
      multiple genes supported its taxonomic status as a distinct species in the genus
      Lactobacillus. The availability of a reliable genome sequence will aid future
      investigations on the industrial applications of L. parakefiri in functional
      foods such as kefir grains.

PMID- 28748135
TI  - Biocatalytic and Bioelectrocatalytic Approaches for the Reduction of Carbon
      Dioxide using Enzymes.
AB  - In the recent decade, CO2 has increasingly been regarded not only as a greenhouse
      gas but even more as a chemical feedstock for carbon-based materials. Different
      strategies have evolved to realize CO2 utilization and conversion into fuels and
      chemicals. In particular, biological approaches have drawn attention, as natural
      CO2 conversion serves as a model for many processes. Microorganisms and enzymes
      have been studied extensively for redox reactions involving CO2. In this review,
      we focus on monitoring nonliving biocatalyzed reactions for the reduction of CO2
      by using enzymes. We depict the opportunities but also challenges associated with
      utilizing such biocatalysts. Besides the application of enzymes with co-factors,
      resembling natural processes, and co-factor recovery, we also discuss
      implementation into photochemical and electrochemical techniques.

PMID- 28748136
TI  - Study on community structure of microbial consortium for the degradation of
      viscose fiber wastewater.
AB  - BACKGROUND: Enrichment culture was applied to obtain microbial consortium from
      activated sludge samples collected from biodegradation system, a chemical fiber
      plant in Hebei Province, China. Bacterial composition and community dynamic
      variation were assessed employing denaturing gradient gel electrophoresis
      fingerprinting technology based on amplified 16S rRNA genes in the entire process
      of enrichment culture for viscose fiber wastewater. RESULTS: Four bacteria named
      as VF01, VF02, VF03, and VF04 were isolated from the microbial consortium
      adopting the spray-plate method. The DNA bands of these four bacteria were
      corresponded to the predominant DNA bands in the electrophoresis pattern. VF01,
      VF02, VF03, and VF04 were phylogenetically closed to Bacillus licheniformis,
      Bacillus subtilis, Paracoccus tibetensis, and Pseudomonas sp. by sequence
      analysis, respectively. The degradation effects for CODCr of single isolated
      strain, mixed strains, and microbial consortium (VF) originally screened from
      viscose fiber wastewater were determined. The degradation ability was as follows:
      microbial consortium (VF) > mixed strains > single isolated strain. Microbial
      consortium (VF) showed the optimum degradation rate of CODCr of 87% on 14th day.
      Degradation of pollutants sped up by bio-augmentation of four strains. The
      molecular weight distribution of organic matter showed that viscose fiber
      wastewater contained a certain amount of large molecular organic matter, which
      could be decomposed into smaller molecular substances by microbial consortium
      (VF). CONCLUSIONS: The microbial consortium (VF) obtained from enrichment culture
      exhibited great potential for CODCr degradation. The screened strains had bio
      augmentation functions and the addition of a mixture of four bacteria could speed
      up the degradation rate of pollutants.

PMID- 28748137
TI  - Unusual fracture in a Durata lead with shock coil fragmentation and cable
      externalization.

PMID- 28748138
TI  - Use of intravenous sotalol in newborns with supraventricular tachycardia.

PMID- 28748139
TI  - Subvalvular catheter ablation of the cavotricuspid isthmus in a patient with
      Ebstein's anomaly and tricuspid valve replacement.

PMID- 28748140
TI  - Para-Hisian atrial tachycardia ablation in a patient with congenitally corrected
      transposition of great vessels.

PMID- 28748141
TI  - Recording of isolated very delayed potentials on the right ventricular epicardium
      in a patient with Brugada syndrome.

PMID- 28748142
TI  - Pulmonary arterial pressure sensing in a patient with left ventricular assist
      device during ventricular arrhythmia.

PMID- 28748143
TI  - Successful fluoroless ablation of an incessant atypical atrial flutter attributed
      to AtriClip usage during mini-MAZE surgery for persistent atrial fibrillation.

PMID- 28748144
TI  - Hemoptysis after five months of cryoballoon ablation: What is the relationship?

PMID- 28748145
TI  - Isolation of the conduction between the Marshall bundle and distal coronary sinus
      and the entire coronary sinus for an atrial tachycardia after catheter ablation
      of atrial fibrillation.

PMID- 28748146
TI  - A sailor's dilemma: A case of preexcitation via a fasciculoventricular pathway.

PMID- 28748147
TI  - Confirmation that MAT1A p.Ala259Val mutation causes autosomal dominant
      hypermethioninemia.
AB  - Methionine adenosyltransferase (MAT) I/III deficiency is an inborn error of
      metabolism caused by mutations in MAT1A, encoding the catalytic subunit of MAT
      responsible for the synthesis of S-adenosylmethionine, and is characterized by
      persistent hypermethioninemia. While historically considered a recessive
      disorder, a milder autosomal dominant form of MAT I/III deficiency occurs, though
      only the most common mutation p.Arg264His has ample evidence to prove dominant
      inheritance. We report a case of hypermethioninemia caused by the p.Ala259Val
      substitution and provide evidence of autosomal dominant inheritance by showing
      both maternal inheritance of the mutation and concomitant hypermethioninemia. The
      p.Ala259Val mutation falls in the dimer interface, and thus likely leads to
      dominant inheritance by a similar mechanism to that described in the previously
      reported dominant negative mutation, that is, by means of interference with
      subunits encoded by the wild-type allele.

PMID- 28748148
TI  - Shifting paradigms for treatment of symptomatic aortic stenosis in lower risk
      populations: role of a newer generation balloon-expandable transcatheter aortic
      valve implantation device.

PMID- 28748149
TI  - The prognostic value of residual coronary stenoses after functionally complete
      revascularisation.
AB  - Fractional flow reserve (FFR) has become the gold standard for functional
      assessment of coronary artery stenosis. Studies have confirmed the superiority of
      FFR guided percutaneous coronary intervention (PCI) compared to angiography
      guided PCI. Due to the high cost of FFR, it is not economically viable for FFR to
      be incorporated into every routine invasive coronary angiography. As a result,
      visual estimation of diameter stenosis on invasive coronary angiography still
      remains the cornerstone for decision making regarding revascularisation treatment
      for patients. This is despite recent studies questioning the "visual functional
      mismatch" between diameter stenosis and FFR in 57% of patients with non-left main
      stenosis. In patients with multivessel disease, complete revascularisation leads
      to improved long term outcomes. However, some lesions classified as significant
      by angiography may not be functionally significant. Kobayashi and colleagues
      demonstrated that after functionally complete revascularization with FFR
      guidance, residual angiographic lesions that are not functionally significant do
      not reflect residual ischemia or predict a worse outcome, supporting functionally
      complete, rather than angiographically complete, revascularization.

PMID- 28748150
TI  - Duration of triple antithrombotic therapy and outcomes among patients undergoing
      percutaneous coronary intervention.

PMID- 28748151
TI  - Mesenchymal stromal cell therapy as treatment for ischemic heart failure: the MSC
      HF study.

PMID- 28748152
TI  - Cardiovascular Diagnosis and Therapy (CDT) Editorial: the Minimalist Immediate
      Mechanical Intervention study.

PMID- 28748153
TI  - Prognostic superiority of coronary artery bypass grafting to percutaneous
      coronary intervention in non-diabetic patients with anatomically complex
      multivessel coronary artery disease.

PMID- 28748154
TI  - Revascularization strategies in patients with ST-segment elevation myocardial
      infarction and multivessel coronary artery disease: urgent or staged?

PMID- 28748155
TI  - How far have we come with bioresorbable vascular scaffolds, and where should we
      go?

PMID- 28748156
TI  - The optimal duration of dual antiplatelet therapy after implantation of drug
      eluting coronary stents: an unanswered question.

PMID- 28748157
TI  - Does successful chronic total occlusion recanalization fail to improve long-term
      survival?

PMID- 28748158
TI  - Bioresorbable vascular scaffolds for complex coronary anatomies: "Icarus' flight"
      for interventional cardiologists?

PMID- 28748159
TI  - Long-term dual antiplatelet therapy and concomitant optimal medical therapy
      following percutaneous coronary intervention.

PMID- 28748160
TI  - Requiem for routine thrombus aspiration.

PMID- 28748161
TI  - Thrombus aspiration in primary percutaneous coronary intervention: still a valid
      option with improved technique in selected patients!

PMID- 28748162
TI  - Editorial to 1-year outcomes of FFRCT-guided care in patients with suspected
      coronary disease.

PMID- 28748163
TI  - The relationship between total ischemic time and mortality in patients with
      STEMI: every second counts.

PMID- 28748164
TI  - A thoughtful use of CT angiography among patients with prior coronary artery
      bypass grafts: more lights than shadows?

PMID- 28748165
TI  - Triple antithrombotic therapy in patients undergoing percutaneous coronary
      intervention: balancing between ischemia and bleeding.

PMID- 28748166
TI  - Assessment of immunomodulatory activity of aqueous extract of Calamus rotang.
AB  - OBJECTIVE: There are a number of medicinal plant products which has been used to
      treat various immunological diseases. Out of these medicinal plants, Calamus
      rotang has shown several medicinal properties including anti-viral, anti
      diabetic, anti-inflammatory effects. Normally, the roots of C. rotang are used in
      various ailments to cure piles, burning sensation, cough, leprosy and bleeding
      disorder and also it was used in the treatment of inflammation. In the present
      study, our group were investigated the immunomodulatory activity of aqueous
      extract of C. rotang root in human whole blood and peripheral blood mononuclear
      cells (PBMC) using hepatitis B vaccine (HBsAg) as an antigen. MATERIALS AND
      METHODS: Variable doses of root aqueous extract (0.5 - 30 mg/ml, 100 ul) was
      administered to human whole blood and PBMC using hepatitis B vaccine containing
      surface antigen (HBsAg; 20 ug/ml, 10 ul) as specific antigen in order to estimate
      the total blood counts in human whole blood and nitric oxide production and CD14
      FITC surface marker from human PBMC. RESULTS: Overall, the results showed that
      roots aqueous extract of C. rotang showed remarkable increase in the number of
      blood counts in human whole blood at lower doses (0.5 mg/ml). In addition, root
      aqueous extract of C. rotang also showed the same pattern in case of nitric oxide
      production and estimation of CD14 FITC surface marker in human PBMC. CONCLUSION:
      Altogether, the results suggest that root aqueous extract of C. rotang showed
      immunomodulatory activity.

PMID- 28748167
TI  - Therapeutic efficacy of rose oil: A comprehensive review of clinical evidence.
AB  - OBJECTIVE: Rose oil is obtained from the petals of difference Rosa species
      especially Rosa centifolia L. and Rosa damascena Mill. Various pharmacological
      properties have been attributed to rose oil. The aim of the present study was to
      review the rose oil therapeutic effects which had been clinically evaluated in
      trial studies. MATERIALS AND METHODS: Google scholar, PubMed, Cochrane Library,
      and Scopus were searched for human studies which have evaluated the therapeutic
      effects of rose oil and published in English language until August 2015. RESULTS:
      Thirteen clinical trials (772 participants) were included in this review. Rose
      oil was administered via inhalation or used topically. Most of the studies (five
      trials) evaluated the analgesic effect of rose oil. Five studies evaluated the
      physiological relaxation effect of rose oil. Anti-depressant, psychological
      relaxation, improving sexual dysfunction, and anti-anxiety effects were the other
      clinical properties reported for rose oil. CONCLUSION: Numerous studies on the
      pharmacological properties of rose oil have been done in animals, but studies in
      humans are few. In this study, it was observed that rose oil had physiological
      and psychological relaxation, analgesic and anti-anxiety effects. To obtain
      conclusive results on the efficacy and safety of rose oil, further clinical
      trials with larger sample size and better designation are required.

PMID- 28748168
TI  - Potentiating effects of Perovskia abrotanoides Karel. on pentobarbital-induced
      sleep.
AB  - OBJECTIVE: Sleeplessness is the most common sleep disorder. In this study the
      hypnotic effect of the hydro-alcoholic extract (HAE) of Perovskia abrotanoides
      Karel. and its water fraction (WF), ethyl acetate fraction (EAF) and n-butanol
      fraction (NBF) were studied in mice. MATERIALS AND METHODS: The test compounds
      were administered intraperitoneally to mice 30 min before the administration of
      sodium pentobarbital (30 mg/kg.). Moreover, the influence of flumazenil on the
      hypnotic effect of the extracts was evaluated. Besides, 30 min after
      administration of HAE, motor coordination (rota-rod test) was assessed.
      Additionally, LD50 for HAE was determined and the possible neurotoxicity of the
      extract was tested in neural PC12 cells. RESULTS: The HAE and NBF decreased the
      latency of sleep (p<0.05), and significantly increased the duration of sleep
      (p<0.05) induced by pentobarbital. These effects of P. abrotanoides were reversed
      by flumazenil. HAE did not affect the animals' performance on the rota-rod test.
      The LD50 value for HAE was found to be 4.8 g/kg. HAE and its fractions did not
      show neurotoxic effects in cultured PC12 cell line. CONCLUSION: The results
      showed that P. abrotanoides significantly potentiated pentobarbital hypnosis
      without toxic effect. Probably, its effects are related to its non-polar
      constituents.

PMID- 28748169
TI  - Evaluation of fibrinolytic and antioxidant effects of Allium elburzense bulb
      extracts.
AB  - OBJECTIVE: Allium elburzense is an endemic plant of the family Amaryllidaceae
      that grows wild in northern Iran with some nutritional and medicinal
      applications. The present study was aimed to investigate the fibrinolytic and
      antioxidant effects of A. elburzense bulb extracts. MATERIALS AND METHODS:
      Hydroalcoholic, aqueous, chloroformic and butanolic extracts were evaluated in
      this research. In vitro antioxidant assays were performed using total phenolic,
      DPPH, and FRAP methods. In the in vivo analysis, animals received i.p. injection
      of A. elburzense hydroalcoholic extract for 21 days and hydroperoxides level,
      FRAP value, PT and aPTT were determined in serum samples. The fibrinolytic
      activity of different extracts was quantitatively evaluated by measurement of
      clot weight. RESULTS: In vitro antioxidant assay showed that A. elburzense
      aqueous extract had the highest DPPH scavenging and the highest total antioxidant
      capacity. In the in vivo assay, A. elburzense hydroalcoholic extract reduced
      serum hydroperoxides level and increased serum total antioxidant capacity in
      rats. In vitro fibrinolytic assay revealed remarkable thrombolytic activity for
      this plant with the highest effect for the aqueous extract. However, coagulation
      parameters including PT and aPTT were not affected by administration of A.
      elburzense hydroalcoholic extract in rats. CONCLUSION: In conclusion, the results
      of this study revealed the potential antioxidant and fibrinolytic effects of A.
      elburzense bulb extracts. For developing novel thrombolytic agents, further
      investigations for isolation of bioactive constituents and finding the underlying
      mechanisms are suggested.

PMID- 28748170
TI  - The effects of setarud on the immunological status of HIV-positive patients:
      Efficacy of a novel multi-herbal drug.
AB  - OBJECTIVE: This study examines the effect of the addition of IMOD, a novel multi
      herbal drug to the highly active anti-retroviral therapy (HAART) regimen, on the
      immunological status of HIV-positive patients. MATERIALS AND METHODS: A
      randomized two-parallel-group (HAART group versus HAART+IMOD group), pretest
      posttest design was used.Sixty patients with indications for treatment with the
      HAART regimen participated. One week before and 2 days after the treatments,
      immunological parameters including total lymphocyte count (TLC) and CD4 cell
      count were assessed.The intervention group received the HAART regimen plus IMOD
      every day for 3 months. The control group received only the HAART regimen every
      day for 3 months. RESULTS: In the intervention group, a significant difference
      was observed in CD4between before and after drug therapy (CD4 was increased).
      However, in the control group, the difference in CD4 was not significant before
      and after drug therapy. The difference in TLC was not significantly different
      between the two groups before and after therapy. Nevertheless, TLC was higher in
      the intervention group. CONCLUSION: IMOD (as a herbal drug) has been successfully
      added to the HAART regimen to improve the immunological status of HIV-positive
      patients.

PMID- 28748171
TI  - Effect of linalool on the acquisition and reinstatement of morphine-induced
      conditioned place preference in mice.
AB  - OBJECTIVE: The effect of linalool, a terpene alcohol found in many plants, which
      inhibits NMDA receptors, on the acquisition and reinstatement of morphine-induced
      conditioned place preference (CPP) was evaluated in mice. MATERIAL AND METHODS:
      The effects of different doses of linalool (12.5, 25 and 50 mg/kg, i.p.),
      memantine (20 mg/kg, an NMDA receptor antagonist) and saline, in CPP induced by
      40 mg/kg of morphine were investigated in mice. In another experiment, a single
      injection of morphine (10 mg/kg) reinstated the place reference following
      extinction of a place preference induced by morphine (40 mg/kg). Linalool (12.5,
      25 and 50 mg/kg, i.p.), memantine (20 mg/kg) and saline were administrated 30 min
      before this priming dose of morphine. RESULTS: In the first experiment, linalool
      (12.5 and 50 mg/kg) was able to decrease morphine-induced CPP. In the second
      part, linalool (25 and 50 mg/kg) reduced morphine-induced reinstatement of place
      preference. Both acquisition and reinstatement of morphine-induced CPP, were
      considerably decreased by memantine. CONCLUSION: The present study showed that
      linalool is able to reduce the acquisition and reinstatement of morphine-induced
      CPP which might be due tothrough NMDA receptors blocking.

PMID- 28748172
TI  - Protective effect of Tribulus terrestris fruit extract on cerulein-induced acute
      pancreatitis in mice.
AB  - OBJECTIVE: Antioxidant, anti-inflammatory, analgesic and antimicrobial activities
      of Tribulus terrestris (T. terrestris) could be helpful in the treatment of acute
      pancreatitis; thus, this study was designed to investigate the effects of T.
      terrestris on cerulein-induced acute pancreatitis in mice. MATERIALS AND METHODS:
      Three doses (100, 200 and 400 mg/kg) of T. terrestris hydro-alcoholic extract
      were administered both orally (60 minutes before pancreatitis induction, p.o.)
      and intra-peritoneally (30 minutes before pancreatitis induction, i.p.) to
      different groups of mice (n=6). Pancreatitis was induced by five injections
      (i.p.) of cerulein 50MUg/kg body weight with 1 hr intervals. Animals were
      euthanized 5 hr after the last injection of cerulein and tissue injures were
      assessed biochemically and pathologically. RESULTS: T. terrestris extract 200 and
      400mg/kg (p.o.) and T. terrestris extract 400 mg/kg (i.p.) reduced pancreatic
      tissue myeloperoxidase (MPO) activity and serum amylase and lipase levels and
      alleviated histological parameters. CONCLUSION: These data suggest that T.
      terrestris hydro-alcoholic extract was effective in protecting against
      experimental acute pancreatitis and possibly the efficacy depends on dose and
      route of administration.

PMID- 28748173
TI  - Stereological investigation of the effect of Elaeagnus angustifolia fruit
      hydroalcoholic extract on osteoporosis in ovariectomized rats.
AB  - OBJECTIVE: Postmenopausal osteoporosis is characterized by increased fracture
      risk. However, each approved treatment has specific side effects. Therefore,
      foods with plant origins have increasingly attracted attention as an alternative
      treatment. Studies have shown that Elaeagnus angustifolia (EA) has antioxidant
      properties. The present study aimed to investigate the effects of EA
      hydroalcoholic extract on ovariectomy-induced osteoporosis in rats using
      stereological methods. MATERIAL AND METHODS: 55 female Sprague-Dawley rats were
      randomly assigned to control, sham operated (normal saline), ovariectomized
      (OVX), OVX + EA fruit extract (600 mg/kg BW/day), and OVX + estradiol benzoate (3
      mg/kg BW) for 16 weeks. Blood samples were collected to measure calcium,
      phosphorus, and alkaline phosphatase (ALP) plasma levels. Then, specimens from
      tibia and fifth lumbar vertebra (L5) bones were prepared and stereological
      analysis was done. RESULTS: Ovariectomy significantly decreased the calcium level
      and increased the ALP level in the OVX group. In spite of improvement in calcium
      hemostasis in groups treated with estrogen and EA fruit extract (p<0.05), only
      treatment with estrogen was able to reduce ALP levels. Moreover, treatment with
      EA fruit extract and estrogen caused a significant increase in the number of
      osteoblasts in vertebra and tibia compared to the OVX group (p<0.05). Estrogen
      and EA fruit extract were also able to reduce the number of osteoclasts in tibia
      of the treated OVX rats (p<0.05). CONCLUSION: The results showed that EA extract
      exerted more effects, markedly, on osteoblastogenesis in the OVX rats. Thus, it
      could be considered as a potential agent to treat patients with osteoporosis.

PMID- 28748174
TI  - Antiplasmodial activity and cytotoxicity of ethanol extract of Zea mays root.
AB  - OBJECTIVE: Zea mays root decoction that has been traditionally used for the
      treatment of malaria by various tribes in Nigeria, was evaluated for antimalarial
      potential against malaria parasites using in vivo and in vitro models. MATERIALS
      AND METHODS: The root extract of Zea mays was investigated for antimalarial
      activity against Plasmodium berghei in mice using rodent malaria models;
      suppressive, prophylactic and curative tests and in vitro antiplasmodial activity
      against chloroquine-sensitive (Pf 3D7) and resistant (Pf INDO) strains of
      Plasmodium falciparum using SYBR green assay method. Median lethal dose and
      cytotoxic activity against HeLa and HEKS cells were assessed and phytochemical
      screening was also carried out using standard procedures. RESULTS: The LD50 value
      of root extract was found to be 474.34 mg/kg. The crude extract (45-135 mg/kg,
      p.o) showed significant (p<0.05-0.001) antimalarial activity against P. berghei
      infection in suppressive, prophylactic and curative tests with a prolonged
      survival time. The crude extract also showed moderate activity against both
      chloroquine-sensitive (Pf 3D7) and resistant (Pf INDO) strains of P. falciparum
      with an IC50 value of 71.62+/-3.38 MUg/ml (for Pf 3D7) and 63.76+/-4.12 MUg/ml
      (for Pf INDO). The crude extract was not cytotoxic to the two cell lines tested
      with TC50 of >100 MUg/ml against both HeLa and HEKS cell lines. CONCLUSION: These
      results suggest that the root extract of Zea mays possesses antimalarial activity
      against both chloroquine-sensitive and resistant malaria and these data justify
      its use in ethnomedicine to treat malaria infections.

PMID- 28748175
TI  - Inhibition of the Quorum Sensing System (ComDE Pathway) by Aromatic 1,3-di-m
      tolylurea (DMTU): Cariostatic Effect with Fluoride in Wistar Rats.
AB  - Dental caries occurs as a result of dysbiosis among commensal and pathogenic
      bacteria leading to demineralization of enamel within a dental biofilm (plaque)
      as a consequence of lower pH in the oral cavity. In our previous study, we have
      reported 1,3-disubstituted ureas particularly, 1,3-di-m-tolylurea (DMTU) could
      inhibit the biofilm formation along with lower concentrations of fluoride (31.25
      ppm) without affecting bacterial growth. In the present study, RT-qPCR analysis
      showed the target specific molecular mechanism of DMTU. In vivo treatment with
      DMTU, alone or in combination with fluoride, resulted in inhibition of caries
      (biofilm development of Streptococcus mutans) using a Wistar rat model for dental
      caries. The histopathological analysis reported the development of lesions on
      dentine in infected subjects whereas the dentines of treated rodents were found
      to be intact and healthy. Reduction in inflammatory markers in rodents' blood and
      liver samples was observed when treated with DMTU. Collectively, data speculate
      that DMTU is an effective anti-biofilm and anti-inflammatory agent, which may
      improve the cariostatic properties of fluoride.

PMID- 28748176
TI  - Global Epidemiology of Dengue Outbreaks in 1990-2015: A Systematic Review and
      Meta-Analysis.
AB  - Dengue is an arthropod-borne infectious disease caused by dengue virus (DENV)
      infection and transmitted by Aedes mosquitoes. Approximately 50-100 million
      people are infected with DENV each year, resulting in a high economic burden on
      both governments and individuals. Here, we conducted a systematic review and meta
      analysis to summarize information regarding the epidemiology, clinical
      characteristics, and serotype distribution and risk factors for global dengue
      outbreaks occurring from 1990 to 2015. We searched the PubMed, Embase and Web of
      Science databases through December 2016 using the term "dengue outbreak." In
      total, 3,853 studies were identified, of which 243 studies describing 262 dengue
      outbreaks met our inclusion criteria. The majority of outbreak-associated dengue
      cases were reported in the Western Pacific Region, particularly after the year
      2010; these cases were primarily identified in China, Singapore and Malaysia. The
      pooled mean age of dengue-infected individuals was 30.1 years; of the included
      patients, 54.5% were male, 23.2% had DHF, 62.0% had secondary infections, and
      1.3% died. The mean age of dengue patients reported after 2010 was older than
      that of patients reported before 2010 (34.0 vs. 27.2 years); however, the
      proportions of patients who had DHF, had secondary infections and died
      significantly decreased after 2010. Fever, malaise, headache, and asthenia were
      the most frequently reported clinical symptoms and signs among dengue patients.
      In addition, among the identified clinical symptoms and signs, positive
      tourniquet test (OR = 4.86), ascites (OR = 13.91) and shock (OR = 308.09) were
      identified as the best predictors of dengue infection, DHF and mortality,
      respectively (both P < 0.05). The main risk factors for dengue infection, DHF and
      mortality were living with uncovered water container (OR = 1.65), suffering from
      hypotension (OR = 6.18) and suffering from diabetes mellitus (OR = 2.53),
      respectively (all P < 0.05). The serotype distribution varied with time and
      across WHO regions. Overall, co-infections were reported in 47.7% of the
      evaluated outbreaks, and the highest pooled mortality rate (2.0%) was identified
      in DENV-2 dominated outbreaks. Our study emphasizes the necessity of implementing
      programs focused on targeted prevention, early identification, and effective
      treatment.

PMID- 28748177
TI  - Hypoglycemic effects of tramadol analgesia in hospitalized patients: a case
      control study.
AB  - BACKGROUND: In outpatient populations, hypoglycemia has been associated with
      tramadol. We sought to determine the magnitude of risk for hypoglycemia
      associated with tramadol use in hospitalized patients. METHODS: During a 2-year
      period of observation, adult inpatients who received >=1 dose of tramadol were
      identified and their medical records were reviewed. Patients were included if
      they had blood or plasma glucose (BG) concentrations measured on at least two
      occasions within five days after the initial administration of tramadol. A
      contemporary comparator group of hospitalized oxycodone recipients was similarly
      reviewed. RESULTS: Tramadol was administered to 2927 patients who met inclusion
      criteria. Among these, hypoglycemia (BG <=70 mg/dL) was documented in 22 (46.8%)
      of 47 patients with type 1 diabetes, 113 (16.8%) of 673 patients with type 2
      diabetes, and 103 (4.7%) of 2207 patients who did not have a diabetes mellitus
      diagnosis. In those without a diabetes diagnosis, the causality association
      between hypoglycemia and tramadol use was probable in 77 patients (3.5%). By
      comparison, hypoglycemia was documented in 8 (1.1%) of 716 matched oxycodone
      recipients without diabetes (p = 0.002). As compared with tramadol recipients who
      did not develop low BG concentrations, those who experienced tramadol-related
      hypoglycemia were relatively young (mean age 52.0 versus 59.8 years; p = 0.027)
      and predominantly female (74.0% versus 59.8%; p = 0.012). CONCLUSIONS: Tramadol
      use was causally associated with hypoglycemia in hospitalized patients. The
      proportion of patients without diabetes who developed hypoglycemia was higher
      among those who received tramadol than among those who received oxycodone. TRIAL
      REGISTRATION: Colorado Multiple Institutional Review Board Protocol No 15-2215.
      Registered/approved 8 December 2015.

PMID- 28748178
TI  - Community-Based Prescribing for Impetigo in Remote Australia: An Opportunity for
      Antimicrobial Stewardship.
AB  - BACKGROUND: To support antibiotic prescribing for both hospital and community
      based health professionals working in remote North Western Australia, a
      multidisciplinary Antimicrobial Stewardship (AMS) Committee was established in
      2013. This Committee is usually focused on hospital-based prescribing. A
      troubling increase in sulfamethoxazole/trimethoprim resistance in Staphylococcus
      aureus antibiograms from 9 to 18% over 1 year prompted a shift in gaze to
      community prescribing. WHAT WE DID: Finding a paucity of relevant research, we
      first investigated contextual factors influencing local prescribing. We also
      designed a systematic survey of experts with experience relevant to our setting
      using a structured response survey (12 questions) to better understand specific
      AMS risks. Using these findings, recommendations were formulated for the AMS
      Committee. WHAT WE LEARNED: Prescribing recommendations in a regional Skin
      Infections Protocol had previously been altered in December 2014. From 15
      experts, we received 9 comprehensive responses (60%) about AMS risks in community
      prescribing. If feasible, prescribing audits also would have been valuable. Ten
      recommendations regarding specific antibiotic recommendations were submitted to
      the AMS Committee. STRENGTHENING AMS IN REMOTE SETTINGS: As AMS Committees in
      Australia usually focus on hospital-based prescribing, novel methods such as
      external expert opinion could inform deliberations about community-based
      prescribing. Our approach meant that this AMS Committee was able to intervene in
      the 2017 organizational review of the regional Skin Infections Protocol used by
      prescribers likely unaware of AMS risks. This experience demonstrates the value
      of incorporating AMS principles in community-based prescribing in context of a
      remote setting.

PMID- 28748179
TI  - Structure-Activity Relationships of Insect Defensins.
AB  - Insects make up the largest and most diverse group of organisms on earth with
      several million species to exist in total. Considering the sheer number of insect
      species and the vast variety of ways they interact with their environment through
      chemistry, it is clear that they have significant potential as a source of new
      lead molecules. They have adapted to a range of ecological habitats and exhibit a
      symbiotic lifestyle with various microbes such as bacteria and fungi.
      Accordingly, numerous antimicrobial compounds have been identified including for
      example defensin peptides. Insect defensins were found to have broad-spectrum
      activity against various gram-positive/negative bacteria as well as fungi. They
      exhibit a unique structural topology involving the complex arrangement of three
      disulfide bonds as well as an alpha helix and beta sheets, which is known as
      cysteine-stabilized alphabeta motif. Their stability and amenability to peptide
      engineering make them promising candidates for the development of novel
      antibiotics lead molecules. This review highlights the current knowledge
      regarding the structure-activity relationships of insect defensin peptides and
      provides basis for future studies focusing on the rational design of novel
      cysteine-rich antimicrobial peptides.

PMID- 28748181
TI  - Great Challenges in Organic Chemistry.

PMID- 28748180
TI  - Buwchitin: A Ruminal Peptide with Antimicrobial Potential against Enterococcus
      faecalis.
AB  - Antimicrobial peptides (AMPs) are gaining popularity as alternatives for
      treatment of bacterial infections and recent advances in omics technologies
      provide new platforms for AMP discovery. We sought to determine the antibacterial
      activity of a novel antimicrobial peptide, buwchitin, against Enterococcus
      faecalis. Buwchitin was identified from a rumen bacterial metagenome library,
      cloned, expressed and purified. The antimicrobial activity of the recombinant
      peptide was assessed using a broth microdilution susceptibility assay to
      determine the peptide's killing kinetics against selected bacterial strains. The
      killing mechanism of buwchitin was investigated further by monitoring its ability
      to cause membrane depolarization (diSC3(5) method) and morphological changes in
      E. faecalis cells. Transmission electron micrographs of buwchitin treated E.
      faecalis cells showed intact outer membranes with blebbing, but no major damaging
      effects and cell morphology changes. Buwchitin had negligible cytotoxicity
      against defibrinated sheep erythrocytes. Although no significant membrane leakage
      and depolarization was observed, buwchitin at minimum inhibitory concentration
      (MIC) was bacteriostatic against E. faecalis cells and inhibited growth in vitro
      by 70% when compared to untreated cells. These findings suggest that buwchitin, a
      rumen derived peptide, has potential for antimicrobial activity against E.
      faecalis.

PMID- 28748182
TI  - Mycobacteria Modify Their Cell Size Control under Sub-Optimal Carbon Sources.
AB  - The decision to divide is the most important one that any cell must make. Recent
      single cell studies suggest that most bacteria follow an "adder" model of cell
      size control, incorporating a fixed amount of cell wall material before dividing.
      Mycobacteria, including the causative agent of tuberculosis Mycobacterium
      tuberculosis, are known to divide asymmetrically resulting in heterogeneity in
      growth rate, doubling time, and other growth characteristics in daughter cells.
      The interplay between asymmetric cell division and adder size control has not
      been extensively investigated. Moreover, the impact of changes in the environment
      on growth rate and cell size control have not been addressed for mycobacteria.
      Here, we utilize time-lapse microscopy coupled with microfluidics to track live
      Mycobacterium smegmatis cells as they grow and divide over multiple generations,
      under a variety of growth conditions. We demonstrate that, under optimal
      conditions, M. smegmatis cells robustly follow the adder principle, with constant
      added length per generation independent of birth size, growth rate, and inherited
      pole age. However, the nature of the carbon source induces deviations from the
      adder model in a manner that is dependent on pole age. Understanding how
      mycobacteria maintain cell size homoeostasis may provide crucial targets for the
      development of drugs for the treatment of tuberculosis, which remains a leading
      cause of global mortality.

PMID- 28748183
TI  - Neodymium-140 DOTA-LM3: Evaluation of an In Vivo Generator for PET with a Non
      Internalizing Vector.
AB  - 140Nd (t1/2 = 3.4 days), owing to its short-lived positron emitting daughter
      140Pr (t1/2 = 3.4 min), has promise as an in vivo generator for positron emission
      tomography (PET). However, the electron capture decay of 140Nd is chemically
      disruptive to macrocycle-based radiolabeling, meaning that an in vivo
      redistribution of the daughter 140Pr is expected before positron emission. The
      purpose of this study was to determine how the delayed positron from the de
      labeled 140Pr affects preclinical imaging with 140Nd. To explore the effect,
      140Nd was produced at CERN-ISOLDE, reacted with the somatostatin analogue, DOTA
      LM3 (1,4,7,10- tetraazacyclododecane, 1,4,7- tri acetic acid, 10- acetamide N - p
      Cl-Phecyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2) and
      injected into H727 xenograft bearing mice. Comparative pre- and post-mortem PET
      imaging at 16 h postinjection was used to quantify the in vivo redistribution of
      140Pr following 140Nd decay. The somatostatin receptor-positive pancreas
      exhibited the highest tissue accumulation of 140Nd-DOTA-LM3 (13% ID/g at 16 h)
      coupled with the largest observed redistribution rate, where 56 +/- 7% (n = 4,
      mean +/- SD) of the in situ produced 140Pr washed out of the pancreas before
      decay. Contrastingly, the liver, spleen, and lungs acted as strong sink organs
      for free 140Pr3+. Based upon these results, we conclude that 140Nd imaging with a
      non-internalizing vector convolutes the biodistribution of the tracer with the
      accumulation pattern of free 140Pr. This redistribution phenomenon may show
      promise as a probe of the cellular interaction with the vector, such as in
      determining tissue dependent internalization behavior.

PMID- 28748184
TI  - Complement in Non-Antibody-Mediated Kidney Diseases.
AB  - The complement system is part of the innate immune response that plays important
      roles in protecting the host from foreign pathogens. The complement components
      and relative fragment deposition have long been recognized to be strongly
      involved also in the pathogenesis of autoantibody-related kidney
      glomerulopathies, leading to direct glomerular injury and recruitment of
      infiltrating inflammation pathways. More recently, unregulated complement
      activation has been shown to be associated with progression of non-antibody
      mediated kidney diseases, including focal segmental glomerulosclerosis, C3
      glomerular disease, thrombotic microangiopathies, or general fibrosis generation
      in progressive chronic kidney diseases. Some of the specific mechanisms
      associated with complement activation in these diseases were recently clarified,
      showing a dominant role of alternative activation pathway. Over the last decade,
      a growing number of anticomplement agents have been developed, and some of them
      are being approved for clinical use or already in use. Therefore, anticomplement
      therapies represent a realistic choice of therapeutic approaches for complement
      related diseases. Herein, we review the complement system activation, regulatory
      mechanisms, their involvement in non-antibody-mediated glomerular diseases, and
      the recent advances in complement-targeting agents as potential therapeutic
      strategies.

PMID- 28748185
TI  - Novel Actions of Growth Hormone in Podocytes: Implications for Diabetic
      Nephropathy.
AB  - The kidney regulates water, electrolyte, and acid-base balance and thus maintains
      body homeostasis. The kidney's potential to ensure ultrafiltered and almost
      protein-free urine is compromised in various metabolic and hormonal disorders
      such as diabetes mellitus (DM). Diabetic nephropathy (DN) accounts for ~20-40% of
      mortality in DM. Proteinuria, a hallmark of renal glomerular diseases, indicates
      injury to the glomerular filtration barrier (GFB). The GFB is composed of
      glomerular endothelium, basement membrane, and podocytes. Podocytes are
      terminally differentiated epithelial cells with limited ability to replicate.
      Podocyte shape and number are both critical for the integrity and function of the
      GFB. Podocytes are vulnerable to various noxious stimuli prevalent in a diabetic
      milieu that could provoke podocytes to undergo changes to their unique
      architecture and function. Effacement of podocyte foot process is a typical
      morphological alteration associated with proteinuria. The dedifferentiation of
      podocytes from epithelial-to-mesenchymal phenotype and consequential loss results
      in proteinuria. Poorly controlled type 1 DM is associated with elevated levels of
      circulating growth hormone (GH), which is implicated in the pathophysiology of
      various diabetic complications including DN. Recent studies demonstrate that
      functional GH receptors are expressed in podocytes and that GH may exert
      detrimental effects on the podocyte. In this review, we summarize recent advances
      that shed light on actions of GH on the podocyte that could play a role in the
      pathogenesis of DN.

PMID- 28748187
TI  - De novo Assembly and Characterization of Cajanus scarabaeoides (L.) Thouars
      Transcriptome by Paired-End Sequencing.
AB  - Pigeonpea [Cajanus cajan (L.) Millsp.] is a heat and drought resilient legume
      crop grown mostly in Asia and Africa. Pigeonpea is affected by various biotic
      (diseases and insect pests) and abiotic stresses (salinity and water logging)
      which limit the yield potential of this crop. However, resistance to all these
      constraints is not readily available in the cultivated genotypes and some of the
      wild relatives have been found to withstand these resistances. Thus, the
      utilization of crop wild relatives (CWR) in pigeonpea breeding has been effective
      in conferring resistance, quality and breeding efficiency traits to this crop.
      Bud and leaf tissue of Cajanus scarabaeoides, a wild relative of pigeon pea were
      used for transcriptome profiling. Approximately 30 million clean reads filtered
      from raw reads by removal of adaptors, ambiguous reads and low-quality reads
      (3.02 gigabase pairs) were generated by Illumina paired-end RNA-seq technology.
      All of these clean reads were pooled and assembled de novo into 1,17,007
      transcripts using the Trinity. Finally, a total of 98,664 unigenes were derived
      with mean length of 396 bp and N50 values of 1393. The assembly produced
      significant mapping results (73.68%) in BLASTN searches of the Glycine max CDS
      sequence database (Ensembl). Further, uniprot database of Viridiplantae was used
      for unigene annotation; 81,799 of 98,664 (82.90%) unigenes were finally annotated
      with gene descriptions or conserved protein domains. Further, a total of 23,475
      SSRs were identified in 27,321 unigenes. This data will provide useful
      information for mining of functionally important genes and SSR markers for
      pigeonpea improvement.

PMID- 28748188
TI  - Arterial stiffness in symptomatic smokers with normal lung function.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with cardiovascular
      morbidity and mortality. Arterial stiffness and endothelial dysfunction index are
      validated surrogate cardiovascular markers and are increased in subjects with
      COPD. We tested whether increased arterial stiffness and endothelial dysfunction
      occur in symptomatic smokers with no evidence of bronchial obstruction. Clinical
      and lung functional assessments were conducted in smoker subjects with chronic
      respiratory symptoms and in COPD patients. Pulse wave velocity (PWV), aortic
      augmentation index (AIx) and reactive hyperaemia index (RHI) were measured to
      estimate the cardiovascular risk. 48 smokers (male n=37, female n=11; mean age
      70+/-8.4 years) were studied. Smokers with respiratory symptoms without bronchial
      obstruction (n=13) did not differ from COPD patients (n=35) in terms of mean+/-sd
      PWV (12+/-3.2 m.s-1versus 14+/-3.8 m.s-1; p=0.10), aortic AIx (25.2+/-11.8%
      versus 24.8+/-9.7%, p=0.89) and RHI (1.66+/-1.49 versus 1.62+/-1.43; p=0.79). The
      current investigation shows that the cardiovascular risk occurs in smokers with
      respiratory symptoms in the absence of bronchial obstruction. These findings need
      to be confirmed in larger populations in order to inform the design of intensive
      preventive programmes.

PMID- 28748186
TI  - Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis.
AB  - Here, we review the diverse roles and functions of AAA+ protease complexes in
      protein homeostasis, control of stress response and cellular development pathways
      by regulatory and general proteolysis in the Gram-positive model organism
      Bacillus subtilis. We discuss in detail the intricate involvement of AAA+ protein
      complexes in controlling sporulation, the heat shock response and the role of
      adaptor proteins in these processes. The investigation of these protein complexes
      and their adaptor proteins has revealed their relevance for Gram-positive
      pathogens and their potential as targets for new antibiotics.

PMID- 28748189
TI  - Apples and pears? A comparison of two sources of national lung cancer audit data
      in England.
AB  - In 2014, the method of data collection from NHS trusts in England for the
      National Lung Cancer Audit (NLCA) was changed from a bespoke dataset called
      LUCADA (Lung Cancer Data). Under the new contract, data are submitted via the
      Cancer Outcome and Service Dataset (COSD) system and linked additional cancer
      registry datasets. In 2014, trusts were given opportunity to submit LUCADA data
      as well as registry data. 132 NHS trusts submitted LUCADA data, and all 151
      trusts submitted COSD data. This transitional year therefore provided the
      opportunity to compare both datasets for data completeness and reliability. We
      linked the two datasets at the patient level to assess the completeness of key
      patient and treatment variables. We also assessed the interdata agreement of
      these variables using Cohen's kappa statistic, kappa. We identified 26 001
      patients in both datasets. Overall, the recording of sex, age, performance status
      and stage had more than 90% agreement between datasets, but there were more
      patients with missing performance status in the registry dataset. Although levels
      of agreement for surgery, chemotherapy and external-beam radiotherapy were high
      between datasets, the new COSD system identified more instances of active
      treatment. There seems to be a high agreement of data between the datasets, and
      the findings suggest that the registry dataset coupled with COSD provides a
      richer dataset than LUCADA. However, it lagged behind LUCADA in performance
      status recording, which needs to improve over time.

PMID- 28748190
TI  - Management of Patients With Hepatitis C Virus, Monoclonal Gammopathy of
      Undetermined Significance, and Multiple Myeloma.
AB  - Background and Aim: The vast majority of the 2.7 million individuals in the
      United States who are currently infected with hepatitis C virus (HCV) were born
      between 1945 and 1965. The median age of these patients in this particular
      generation at the time of this writing was 55 years. In the general population,
      older age is a risk factor for multiple myeloma (MM) and other monogammopathies.
      As the baby boomer population ages, HCV providers are increasingly likely to
      encounter HCV-infected patients with a monoclonal gammopathy. Guidelines for
      managing these patients are needed. Methods: We conducted a detailed case series
      investigation of 4 HCV-positive patients with MM or a monoclonal gammopathy
      disorder. Patients were followed at the Mount Sinai Faculty Practice liver
      clinic. We also performed a detailed review of the literature exploring if there
      is any known association between HCV, MM, and monoclonal gammopathy. Results and
      Conclusions: There is no convincing evidence of a causal association between HCV
      and MM. HCV is linked to type II and type III cryoglobulinemia, specific kinds of
      monoclonal gammopathies of determinable significance. Whether a link exists
      between HCV and MM or monoclonal gammopathy of undetermined significance is
      unclear. Our case series provides the first evidence that modern HCV treatments
      with direct-acting antivirals can be safely and effectively co-administered with
      MM chemotherapy.

PMID- 28748191
TI  - The Yin and Yang Between Plasma Glucose Levels and Cortisol Replacement Therapy
      in Schmidt's Syndrome.
AB  - Objective: To illustrate how steroid replacement in adrenal insufficiency can
      influence the development of hypoglycemia in a patient with type 1 diabetes
      mellitus (T1D). Methods: We describe the case of a 36-year-old female patient
      with T1D and Addison's disease (Schmidt's syndrome) on multiple daily insulin
      injections who presented with recurrent hypoglycemia despite being on
      physiological replacement doses of hydrocortisone. Results: With the assistance
      of continuous glucose monitoring technology, a pattern of nocturnal hypoglycemia
      was clearly identified. The patient was taking her hydrocortisone 15 mg in the
      morning and 5 mg in the early afternoon. With the short half-life of oral
      hydrocortisone, the evening decline in plasma cortisol concentration led to an
      increased susceptibility to recurrent evening and nocturnal hypoglycemia.
      Hypoglycemic episodes were resolved when her morning hydrocortisone dose was
      changed and prednisolone was added to a later time in the evening. Conclusion:
      Patients with Schmidt's syndrome can be susceptible to nocturnal hypoglycemia
      with inadequate steroid replacement. Identifying patients at risk for
      hypoglycemia in Schmidt's syndrome provides an opportunity for precision
      management beyond the manipulation of antihyperglycemic agents.

PMID- 28748192
TI  - Extranodal NK/T-Cell Lymphoma, Nasal Type, Presenting as Refractory Pseudomonas
      aeruginosa Facial Cellulitis.
AB  - Extranodal natural killer T-cell lymphoma, nasal type (ENKL), formerly called
      lethal midline granuloma or angiocentric T-cell lymphoma, is a predominantly
      extranodal non-Hodgkin lymphoma characterized by vascular damage, necrosis, and
      an association with Epstein-Barr virus. In the United States, it is more
      frequently seen in Asian, Asian Pacific Islander, and Hispanic descent
      populations and is more prevalent in males in their fifth decade. Clinical
      presentation of NK nasal lymphoma most commonly involves epistaxis; obstruction;
      discharge; destructive mass in sinuses, palate, and nose; and skin ulceration.
      These symptoms can mimic invasive fungal infections and other sinonasal
      disorders. Furthermore, ENKL has a broad cytologic spectrum and induces a mixture
      of inflammatory cells, causing difficulty in establishing the diagnosis,
      especially in initial biopsies. We present a case of refractory Pseudomonas
      aeruginosa facial cellulitis in a young woman whose treatment course was
      complicated by septic shock and resistance to multiple antibiotics, resulting in
      a delayed diagnosis of ENKL nasal type.

PMID- 28748193
TI  - Infliximab Therapy Leading to Pulmonary Tuberculosis in a Patient With Negative
      Interferon gamma Release Assay (IGRA)-Based QuantiFERON Gold Test.
AB  - Infliximab therapy is associated with higher rates of active tuberculosis (TB),
      particularly extrapulmonary and disseminated forms with unusual symptoms. We
      report the case of a 66-year-old man with Crohn's disease who developed TB
      mimicking lung cancer on imaging. He presented with cough and fever of 2 weeks'
      duration shortly after starting infliximab. Computed tomography of the chest
      revealed a 7.0 * 3.2 cm2 pleural-based mass, highly suspicious for malignancy.
      Histopathological examination confirmed the diagnosis of TB. The mass disappeared
      after antitubercular treatment, and the patient recovered completely. A review of
      the literature suggests that TB masquerades as lung cancer clinically and
      radiologically. The classical lesions of TB are cavitatory with calcifications.
      Mass lesions without cavity or calcifications are rare and are mostly reported
      from regions endemic for TB. The majority of patients on infliximab therapy
      required biopsy for accurate diagnosis of TB because of its unusual presentation.

PMID- 28748194
TI  - Recurrent Metatarsal Fractures in Postmenopausal Woman With Low Serum Alkaline
      Phosphatase: A Rare Diagnosis Not to Miss.
AB  - Hypophosphatasia (HPP) is a rare inborn error of metabolism due to a loss-of
      function mutation in the gene for tissue nonspecific isoenzyme of alkaline
      phosphatase (ALP) that results in low levels of ALP. The clinical presentation of
      HPP is variable and in adults can easily be misdiagnosed as other forms of
      osteomalacia. We present a case of a 53-year-old Caucasian female who was
      evaluated for recurrent metatarsal fractures. She reported her first metatarsal
      fracture at age 21, and since then had at least 8 more metatarsal fractures over
      her lifetime, most without injury other than weight bearing. She reported history
      of gait disturbance as a child and dental issues (spacing and loosening).
      Laboratory tests showed normal serum calcium, phosphorus, and parathyroid
      hormone, but low serum ALP <20 IU/L and elevated N-telopeptide. Foot X-ray showed
      several healed and nonhealed metatarsal fractures, and bone densitometry revealed
      osteopenia. She was treated with calcium and vitamin D. A year later she had a
      new metatarsal fracture and a nontraumatic pelvic fracture. Teriparatide therapy
      was attempted but not tolerated. Due to suspicion of HPP vitamin B6 levels were
      checked and found to be elevated at 263 ug/L. Given her clinical presentation and
      low ALP levels with elevated vitamin B6, the diagnosis of HPP was made.
      Clinicians should be attentive to a history of recurrent low trauma fractures,
      premature loss of deciduous teeth, and persistently low serum ALP to suspect this
      diagnosis. Early case detection with the availability of recent Food and Drug
      Administration-approved asfotase alfa may avoid years of undiagnosed morbidity.

PMID- 28748195
TI  - Functional Brace in ACL Surgery: Force Quantification in an In Vivo Study.
AB  - BACKGROUND: A need exists for a functional anterior cruciate ligament (ACL) brace
      that dynamically supports the knee joint to match the angle-dependent forces of a
      native ACL, especially in the early postoperative period. PURPOSE/HYPOTHESIS: The
      purpose of this study was to quantify the posteriorly directed external forces
      applied to the anterior proximal tibia by both a static and a dynamic force ACL
      brace. The proximal strap forces applied by the static force brace were
      hypothesized to remain relatively constant regardless of knee flexion angle
      compared with those of the dynamic force brace. STUDY DESIGN: Controlled
      laboratory study. METHODS: Seven healthy adult males (mean age, 27.4 +/- 3.4
      years; mean height, 1.8 +/- 0.1 m; mean body mass, 84.1 +/- 11.3 kg) were fitted
      with both a static and a dynamic force ACL brace. Participants completed 3
      functional activities: unloaded extension, sit-to-stand, and stair ascent.
      Kinematic data were collected using traditional motion-capture techniques while
      posteriorly directed forces applied to the anterior aspect of both the proximal
      and distal tibia were simultaneously collected using a customized pressure
      mapping technique. RESULTS: The mean posteriorly directed forces applied to the
      proximal tibia at 30 degrees  of flexion by the dynamic force brace during
      unloaded extension (80.2 N), sit-to-stand (57.5 N), and stair ascent (56.3 N)
      activities were significantly larger, regardless of force setting, than those
      applied by the static force brace (10.1 N, 9.5 N, and 11.9 N, respectively; P <
      .001). CONCLUSION: The dynamic force ACL brace, compared with the static force
      brace, applied significantly larger posteriorly directed forces to the anterior
      proximal tibia in extension, where the ACL is known to experience larger in vivo
      forces. Further studies are required to determine whether the physiological
      behavior of the brace will reduce anterior knee laxity and improve long-term
      patient outcomes. CLINICAL RELEVANCE: ACL braces that dynamically restrain the
      proximal tibia in a manner similar to physiological ACL function may improve pre-
      and postoperative treatment.

PMID- 28748196
TI  - Developing Interactive Antimicrobial Stewardship and Infection Prevention
      Curricula for Diverse Learners: A Tailored Approach.
AB  - BACKGROUND: To impart principles of antimicrobial stewardship (AS) and infection
      prevention and control (IPC), we developed a curriculum tailored to the diverse
      aptitudes of learners at our medical center. METHODS: We integrated case-based
      modules, group learning activities, smartphone applications (apps), decision
      support tools, and prescription audit and feedback into curricula of the medical
      school, medicine residency program, infectious diseases (ID) fellowship program,
      and hospital medicine program operations. Interventions were implemented in 2012
      2016 using a quasi-experimental before-and-after study design, and this was
      assessed using pre- and postintervention surveys or audit of antibiotic
      prescriptions. RESULTS: Over 180 medical students participated in the AS and IPC
      seminars. After smartphone app introduction, 69% reported using the app as their
      preferred source of antibiotic information. Approximately 70% of students felt
      comfortable prescribing antibiotics for a known infection compared with 40% at
      baseline (P = .02), and approximately 83% were able to identify the appropriate
      personal protective equipment for specific scenarios. Approximately 99% agreed
      that they have a role in promoting patient safety and preventing healthcare
      associated infections as medical students. At 20 months, appropriateness of
      trainee antibiotic prescriptions increased by 20% (P < .01). Almost all ID
      fellows indicated that the AS and IPC seminar was a vital training supplement.
      Uptake of internist antibiotic recommendations using AS decision support tools
      was approximately 70%. CONCLUSIONS: All 5 interventions addressed learning
      objectives and knowledge gaps and are applicable across a range of environments.
      Evaluating long-term impact of our curriculum is the focus of future study.

PMID- 28748197
TI  - Incidence, Long-Term Outcomes, and Healthcare Utilization of Patients With Human
      Immunodeficiency Virus/Acquired Immune Deficiency Syndrome and Disseminated
      Mycobacterium avium Complex From 1992-2015.
AB  - BACKGROUND: Despite the advent of combination antiretroviral therapy (cART),
      patients with human immunodeficiency virus (HIV) continue to develop late-stage
      complications including acquired immune deficiency syndrome (AIDS), disseminated
      Mycobacterium avium complex (DMAC), and death. METHODS: We performed an
      observational retrospective cohort study of HIV-infected adults who developed
      DMAC in the Duke University Health System from 1992 to 2015 to determine the
      incidence, long-term outcomes, and healthcare utilization of this population at
      high risk for poor outcomes. Findings were stratified by the "pre-cART" era
      (before January 1, 1996) and "post-cART" thereafter. RESULTS: We identified 330
      adult HIV-infected patients newly diagnosed with DMAC, the majority (75.2%) of
      whom were male and non-Hispanic black (69.1%), with median age of 37 years.
      Incidence of DMAC declined significantly from 65.3/1000 in 1992 to 2.0/1000 in
      2015, and the proportion of females and non-Hispanic blacks was significantly
      higher in the post-cART era. The standardized mortality ratios for DMAC patients
      who received cART were 69, 58, 27, 5.9, and 6.8 at years 1-5, respectively, after
      DMAC diagnosis. For patients diagnosed with DMAC in 2000 or later (n = 135), 20%
      were newly diagnosed with HIV in the 3 months preceding presentation with DMAC.
      Those with established HIV had a median time from HIV diagnosis to DMAC diagnosis
      of 7 years and were more likely to be black, rehospitalized in the 6 months after
      DMAC diagnosis, and die in the long term. CONCLUSIONS: Disseminated Mycobacterium
      avium complex continues to be a lethal diagnosis in the cART era,
      disproportionately afflicts minority populations, and reflects both delayed entry
      into care and failure to consistently engage care.

PMID- 28748198
TI  - Abacavir/Dolutegravir/Lamivudine (Triumeq)-Induced Liver Toxicity in a Human
      Immunodeficiency Virus-Infected Patient.
AB  - Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir)
      has not been reported in clinical trials. We report a case of hepatotoxicity
      related to Triumeq exposure in a human immunodeficiency virus-infected patient.
      Clinicians should remain aware of the risk for acute and late-onset hepatitis
      with these agents. Close monitoring is recommended.

PMID- 28748200
TI  - Identification of Factors in Regulating a Protein Ubiquitination by
      Immunoprecipitation: a Case Study of TRF2 on Human REST4 Ubiquitination.
AB  - Ubiquitination is the first step of the ubiquitin-proteasome pathway that
      regulates cells for their homeostatic functions and is an enzymatic, protein post
      translational modification process in which ubiquitin is transferred to a target
      protein substrate by a set of three ubiquitin enzymes (Weissman et al., 2011;
      Bhattacharyya et al., 2014; Ristic et al., 2014). Given the importance of this
      process, it is plausible that ubiquitination is under strict control by many
      factors and that the regulatory machineries are protein-specific. An assay for
      the detection of a specific protein ubiquitination will enable us to examine
      whether a factor has a function to regulate the ubiquitination of this protein.
      Here we describe a protocol that detects the ubiquitination status of the human
      REST4 protein in cultured cells, a neural alternative splicing isoform of REST
      (RE-1 silencing transcription factor), that antagonizes the repressive function
      of REST on neural differentiation and neuron formation. Using this protocol, we
      show that the telomere binding protein TRF2 stabilizes the expression of the
      human REST4 by inhibiting its ubiquitination. This indicates that TRF2 plays a
      positive role in neural differentiation (Ovando-Roche et al., 2014). This
      protocol is also useful for the detection of ubiquitination of other proteins of
      interest.

PMID- 28748199
TI  - Current Research Approaches to Target Biofilm Infections.
AB  - This review will focus on strategies to develop new treatments that target the
      biofilm mode of growth and that can be used to treat biofilm infections. These
      approaches aim to reduce or inhibit biofilm formation, or to increase biofilm
      dispersion. Many antibiofilm compounds are not bactericidal but render the cells
      in a planktonic growth state, which are more susceptible to antibiotics and more
      easily cleared by the immune system. Novel compounds are being developed with
      antibiofilm activity that includes antimicrobial peptides, natural products,
      small molecules and polymers. Bacteriophages are being considered for use in
      treating biofilms, as well as the use of enzymes that degrade the extracellular
      matrix polymers to dissolve biofilms. There is great potential in these new
      approaches for use in treating chronic biofilm infections.

PMID- 28748201
TI  - Chlorophyll Content Assay to Quantify the Level of Necrosis Induced by Different
      R Gene/Elicitor Combinations after Transient Expression.
AB  - This assay can be used to rapidly and accurately quantify levels of leaf necrosis
      induced after transient expression of R genes and elicitor combinations (Harris
      et al., 2013). It is based on the inverse correlation between level of necrosis
      and chlorophyll content in leaf tissue. It is adapted from the calculations
      described by (Strain et al., 1971).

PMID- 28748202
TI  - The Repeated Flurothyl Seizure Model in Mice.
AB  - Development of spontaneous seizures is the hallmark of human epilepsy. There is a
      critical need for new epilepsy models in order to elucidate mechanisms
      responsible for leading to the development of spontaneous seizures and for
      testing new anti-epileptic compounds. Moreover, rodent models of epilepsy have
      clearly demonstrated that there are two independent seizure systems in the brain:
      1) the forebrain seizure network required for the expression of clonic seizures
      mediated by forebrain neurocircuitry, and 2) the brainstem seizure network
      necessary for the expression of brainstem or tonic seizures mediated by brainstem
      neurocircuitry. In seizure naive animals, these two systems are separate, but
      developing models that can explore the intersection of the forebrain and
      brainstem seizure systems or for elucidating mechanisms responsible for bringing
      these two seizure systems together may aid in our understanding of: 1) how
      seizures can become more complex overtime, and 2) sudden unexpected death in
      epilepsy (SUDEP) since propagation of seizure discharge from the forebrain
      seizure system to the brainstem seizure system may have an important role in
      SUDEP because many cardiorespiratory systems are localized in the brainstem. The
      repeated flurothyl seizure model of epileptogenesis, as described here, may aid
      in providing insight into these important epilepsy issues in addition to
      understanding how spontaneous seizures develop.

PMID- 28748203
TI  - Thermal Stability of Heterotrimeric pMHC Proteins as Determined by Circular
      Dichroism Spectroscopy.
AB  - T cell receptor (TCR) recognition of foreign peptide fragments, presented by
      peptide major histocompatibility complex (pMHC), governs T-cell mediated
      protection against pathogens and cancer. Many factors govern T-cell sensitivity,
      including the affinity of the TCR-pMHC interaction and the stability of pMHC on
      the surface of antigen presenting cells. These factors are particularly relevant
      for the peptide vaccination field, in which more stable pMHC interactions could
      enable more effective protection against disease. Here, we discuss a method for
      the determination of pMHC stability that we have used to investigate HIV immune
      escape, T-cell sensitivity to cancer antigens and mechanisms leading to
      autoimmunity.

PMID- 28748204
TI  - Data on effects of rotenone on calcium retention capacity, respiration and
      activities of respiratory chain complexes I and II in isolated rat brain
      mitochondria.
AB  - The data presented in this article are related to the research article entitled
      "Rotenone decreases ischemia-induced injury by inhibiting mitochondrial
      permeability transition in mature brains" (Rekuviene et al., 2017) [1]. Data in
      this article present the direct effects of rotenone on calcium retention capacity
      (CRC) in isolated normal cortex and cerebellum mitochondria, effects of rotenone
      intravenous infusion on leak and phosphorylating respiration rates of isolated
      cortex and cerebellum mitochondria, on activities of respiratory chain complexes
      I and II in freezed-thawed/sonicated cortex and cerebellum mitochondria after
      brain ischemia. In addition, detailed experimental procedures of isolation of
      brain mitochondria, measurements of CRC, respiration, activities of respiratory
      chain complexes and H2O2 generation in cortex and cerebellum mitochondria are
      described.

PMID- 28748205
TI  - Dataset demonstrating the temperature effect on average output polarization for
      QCA based reversible logic gates.
AB  - Quantum-dot cellular automata (QCA) is a developing nanotechnology, which seems
      to be a good candidate to replace the conventional complementary metal-oxide
      semiconductor (CMOS) technology. In this article, we present the dataset of
      average output polarization (AOP) for basic reversible logic gates presented in
      Ali Newaz et al. (2016) [1]. QCADesigner 2.0.3 has been employed to analysis the
      AOP of reversible gates at different temperature levels in Kelvin (K) unit.

PMID- 28748206
TI  - The complementarity-determining region sequences in IgY antivenom hypervariable
      regions.
AB  - The data presented in this article are related to the research article entitled
      "Development of IgY antibodies against anti-snake toxins endowed with highly
      lethal neutralizing activity" (da Rocha et al., 2017) [1]. Complementarity
      determining region (CDR) sequences are variable antibody (Ab) sequences that
      respond with specificity, duration and strength to identify and bind to antigen
      (Ag) epitopes. B lymphocytes isolated from hens immunized with Bitis arietans
      (Ba) and anti-Crotalus durissus terrificus (Cdt) venoms and expressing high
      specificity, affinity and toxicity neutralizing antibody titers were used as DNA
      sources. The VLF1, CDR1, CDR2, VLR1 and CDR3 sequences were validated by BLASTp,
      and values corresponding to IgY VL and VH anti-Ba or anti-Cdt venoms were
      identified, registered [Gallus gallus IgY Fv Light chain (GU815099)/Gallus gallus
      IgY Fv Heavy chain (GU815098)] and used for molecular modeling of IgY scFv anti
      Ba. The resulting CDR1, CDR2 and CDR3 sequences were combined to construct the
      three - dimensional structure of the Ab paratope.

PMID- 28748207
TI  - Ultrasound data for laboratory calibration of an analytical model to calculate
      crack depth on asphalt pavements.
AB  - This article outlines the ultrasound data employed to calibrate in the laboratory
      an analytical model that permits the calculation of the depth of partial-depth
      surface-initiated cracks on bituminous pavements using this non-destructive
      technique. This initial calibration is required so that the model provides
      sufficient precision during practical application. The ultrasonic pulse transit
      times were measured on beam samples of different asphalt mixtures (semi-dense
      asphalt concrete AC-S; asphalt concrete for very thin layers BBTM; and porous
      asphalt PA). The cracks on the laboratory samples were simulated by means of
      notches of variable depths. With the data of ultrasound transmission time ratios,
      curve-fittings were carried out on the analytical model, thus determining the
      regression parameters and their statistical dispersion. The calibrated models
      obtained from laboratory datasets were subsequently applied to auscultate the
      evolution of the crack depth after microwaves exposure in the research article
      entitled "Top-down cracking self-healing of asphalt pavements with steel filler
      from industrial waste applying microwaves" (Franesqui et al., 2017) [1].

PMID- 28748208
TI  - Dataset of Sgo1 expression in cardiac, gastrointestinal, hepatic and neuronal
      tissue in mouse.
AB  - The data shown in this article are related to the research article entitled
      "Characterization of Sgo1 expression pattern in developing and adult mouse" (Song
      et al., 2017) [3]. The article provides novel data on Sgo1 gene expression
      pattern utilizing Sgo1_LacZ_Knock in mouse line and immunohistochemistry in wild
      type mice. The data presents Sgo1 expression pattern during development, and in
      post-developmental proliferative and quiescent tissue. The article describes
      following tissues: developing heart, neural tube, adult colon, cerebellum,
      cerebral cortex, liver, and testis.

PMID- 28748209
TI  - Metagenomic data of free cyanide and thiocyanate degrading bacterial communities.
AB  - The data presented in this article contains the bacterial community structure of
      the free cyanide (CN-) and thiocyanate (SCN-) degrading organisms that were
      isolated from electroplating wastewater and synthetic SCN- containing wastewater.
      PCR amplification of the 16S rRNA V1-V3 regions was undertaken using the 27F and
      518R oligonucleotide primers following the metacommunity DNA extraction
      procedure. The PCR amplicons were processed using the illumina(r) reaction kits
      as per manufacturer's instruction and sequenced using the illumina(r) MiSeq-2000,
      using the MiSeq V3 kit. The data was processed using bioinformatics tools such as
      QIIME and the raw sequence files are available via NCBI's Sequence Read Archive
      (SRA) database.

PMID- 28748210
TI  - Dataset on genetic and physiological adults' responses to social distress.
AB  - Both expectations towards interactions with conspecifics, and genetic
      predispositions, affect adults' social behaviors. However, the underlying
      mechanisms remain largely unknown. Here, we report data to investigate the
      interaction between genetic factors, (oxytocin receptor (OXTR) and serotonin
      transporter (5-HTTLPR) polymorphisms), and adult interactional patterns in
      shaping physiological responses to social distress. During the presentation of
      distress vocalizations (cries of human female, infants and bonobos) we assessed
      participants' (N = 42 males) heart rate (HR) and peripheral nose temperature,
      which index state of arousal and readiness to action. Self-reported
      questionnaires were used to evaluate participants' interactional patterns towards
      peers (Attachment Style Questionnaire, Feeney et al., 1994[1]), and the quality
      of bond with intimate partners (Experiences in Close Relationships Scale, Fraley
      et al., 2000 [2]). To assess participants' genetic predispositions, the OXTR gene
      (regions rs53576, and rs2254298) and the 5-HTTLPR gene (region SLC6A4) were
      genotyped. The data set is made publicly available to enable critical or extended
      analyzes.

PMID- 28748211
TI  - Granulomatous slack skin presenting as diffuse poikiloderma and necrotic ulcers,
      with features of granulomatous vasculitis and response to oral prednisone,
      acitretin, and oral psoralen plus ultraviolet light therapy-A case report.

PMID- 28748212
TI  - Genetically Engineered Multilineage-Differentiating Stress-Enduring Cells as
      Cellular Vehicles against Malignant Gliomas.
AB  - Malignant glioma, the most common malignant brain tumor in adults, is difficult
      to treat due to its aggressive invasive nature. Enzyme/prodrug suicide gene
      therapy based on the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir
      (GCV) system is an efficient strategy for treating malignant gliomas. In the
      present study, we evaluated treatment with multilineage-differentiating stress
      enduring (Muse) cells, which are endogenous non-tumorigenic pluripotent-like stem
      cells that are easily collectable from the bone marrow as SSEA-3+ cells, as
      carriers of the HSVtk gene. Human Muse cells showed potent migratory activity
      toward glioma cells both in vitro and in vivo. HSVtk gene-transduced Muse cells
      (Muse-tk cells) at a cell number of only 1/32 that of U87 human glioma cells
      completely eradicated U87 gliomas in nude mouse brains, showing a robust in vivo
      bystander effect. Pre-existing intracranial U87 gliomas in nude mouse brains
      injected intratumorally with Muse-tk cells followed by intraperitoneal GCV
      administration were significantly reduced in size within 2 weeks, and 4 of 10
      treated mice survived over 200 days. These findings suggest that intratumoral
      Muse-tk cell injection followed by systemic GCV administration is safe and
      effective and that allogeneic Muse-tk cell-medicated suicide gene therapy for
      malignant glioma is clinically feasible.

PMID- 28748213
TI  - Metabolic reprogramming underlies metastatic potential in an obesity-responsive
      murine model of metastatic triple negative breast cancer.
AB  - The vast majority of cancer-related deaths are due to metastatic disease, whereby
      primary tumor cells disseminate and colonize distal sites within the body. Triple
      negative breast cancer typically displays aberrant Wnt signaling, lacks effective
      targeted therapies, and compared with other breast cancer subtypes, is more
      likely to recur and metastasize. We developed a Wnt-driven lung metastasis model
      of triple negative breast cancer (metM-Wntlung) through serial passaging of our
      previously described, nonmetastatic, claudin-low M-Wnt cell line. metM-Wntlung
      cells displayed characteristics of epithelial-to-mesenchymal transition (e.g.,
      increased invasiveness) with some re-epithealization (e.g., increased adhesion,
      tight colony formation, increased E-cadherin expression, and decreased Vimentin
      and Fibronectin expression). When orthotopically transplanted into syngeneic
      mice, metM-Wntlung cells readily formed tumors and metastasized in vivo, and
      tumor growth and metastasis were enhanced in obese mice compared with non-obese
      mice. Gene expression analysis revealed several genes and pathways altered in
      metM-Wntlung cells compared with M-Wnt cells, including multiple genes associated
      with epithelial-to-mesenchymal transition, energy metabolism and inflammation.
      Moreover, obesity caused significant transcriptomic changes, especially in
      metabolic pathways. Metabolic flux analyses showed greater metabolic plasticity,
      with heightened mitochondrial and glycolytic energetics in metM-Wntlung cells
      relative to M-Wnt cells. Similar metabolic profiles were found in a second triple
      negative breast cancer progression series, M6 and M6C cells. These findings
      suggest that metabolic reprogramming is a feature of metastatic potential in
      triple negative breast cancer. Thus, targeting metastases-associated metabolic
      perturbations may represent a novel strategy for reducing the burden of
      metastatic triple negative breast cancer, particularly in obese women.

PMID- 28748214
TI  - Functionally pathogenic EARS2 variants in vitro may not manifest a phenotype in
      vivo.
AB  - OBJECTIVE: To investigate the genetic etiology of a patient diagnosed with
      leukoencephalopathy, brain calcifications, and cysts (LCC). METHODS: Whole-exome
      sequencing was performed on a patient with LCC and his unaffected family members.
      The variants were subject to in silico and in vitro functional testing to
      determine pathogenicity. RESULTS: Whole-exome sequencing uncovered compound
      heterozygous mutations in EARS2, c.328G>A (p.G110S), and c.1045G>A (p.E349K).
      This gene has previously been implicated in the autosomal recessive
      leukoencephalopathy with thalamus and brainstem involvement and high lactate
      (LTBL). The p.G110S mutation has been found in multiple patients with LTBL. In
      silico analysis supported pathogenicity in the second variant. In vitro
      functional testing showed a significant mitochondrial dysfunction demonstrated by
      an ~11% decrease in the oxygen consumption rate and ~43% decrease in the maximum
      respiratory rate in the patient's skin fibroblasts compared with the control.
      EARS2 protein levels were reduced to 30% of normal controls in the patient's
      fibroblasts. These deficiencies were corrected by the expression of the wild-type
      EARS2 protein. However, a further unrelated genetic investigation of our patient
      revealed the presence of biallelic variants in a small nucleolar RNA (SNORD118)
      responsible for LCC. CONCLUSIONS: Here, we report seemingly pathogenic EARS2
      mutations in a single patient with LCC with no biochemical or neuroimaging
      presentations of LTBL. This patient illustrates that variants with demonstrated
      impact on protein function should not necessarily be considered clinically
      relevant. CLINICALTRIALSGOV IDENTIFIER: NCT00001671.

PMID- 28748215
TI  - This variant alters protein function, but is it pathogenic?

PMID- 28748216
TI  - T cells targeting neuromyelitis optica autoantigen aquaporin-4 cause paralysis
      and visual system injury.
AB  - Aquaporin-4 (AQP4)-specific antibodies are instrumental in promoting central
      nervous system (CNS) tissue injury in neuromyelitis optica (NMO), yet evidence
      indicates that AQP4-specific T cells also have a pivotal role in NMO
      pathogenesis. Although considerable effort has been devoted to creation of animal
      models to study how AQP4-specific T cells and antibodies may cooperate in
      development of both clinical and histologic opticospinal inflammatory disease,
      the initial attempts were unsuccessful. Recently, it was discovered that T cells
      from AQP4-deficient (AQP4-/-) mice recognize distinct AQP4 epitopes that were not
      identified previously in wild-type (WT) mice, and that donor Th17 cells from AQP4
      /- mice that target those novel epitopes could cause paralysis and visual system
      injury associated with opticospinal inflammation in WT recipient mice. These
      observations indicate that the pathogenic AQP4-specific T cell repertoire is
      normally controlled by negative selection. Here, we describe the advances leading
      to development of an animal model for aquaporin-targeted CNS autoimmunity (ATCA).
      This new model provides a foundation to investigate immune mechanisms that may
      participate in NMO pathogenesis. It should also permit preclinical testing of
      agents considered for treatment of NMO.

PMID- 28748217
TI  - Mechanisms and applications of the anti-inflammatory effects of
      photobiomodulation.
AB  - Photobiomodulation (PBM) also known as low-level level laser therapy is the use
      of red and near-infrared light to stimulate healing, relieve pain, and reduce
      inflammation. The primary chromophores have been identified as cytochrome c
      oxidase in mitochondria, and calcium ion channels (possibly mediated by light
      absorption by opsins). Secondary effects of photon absorption include increases
      in ATP, a brief burst of reactive oxygen species, an increase in nitric oxide,
      and modulation of calcium levels. Tertiary effects include activation of a wide
      range of transcription factors leading to improved cell survival, increased
      proliferation and migration, and new protein synthesis. There is a pronounced
      biphasic dose response whereby low levels of light have stimulating effects,
      while high levels of light have inhibitory effects. It has been found that PBM
      can produce ROS in normal cells, but when used in oxidatively stressed cells or
      in animal models of disease, ROS levels are lowered. PBM is able to up-regulate
      anti-oxidant defenses and reduce oxidative stress. It was shown that PBM can
      activate NF-kB in normal quiescent cells, however in activated inflammatory
      cells, inflammatory markers were decreased. One of the most reproducible effects
      of PBM is an overall reduction in inflammation, which is particularly important
      for disorders of the joints, traumatic injuries, lung disorders, and in the
      brain. PBM has been shown to reduce markers of M1 phenotype in activated
      macrophages. Many reports have shown reductions in reactive nitrogen species and
      prostaglandins in various animal models. PBM can reduce inflammation in the
      brain, abdominal fat, wounds, lungs, spinal cord.

PMID- 28748218
TI  - Autophagy regulated by miRNAs in colorectal cancer progression and resistance.
AB  - The catabolic process of autophagy is an essential cellular function that allows
      for the breakdown and recycling of cellular macromolecules. In recent years, the
      impact of epigenetic regulation of autophagy by non-coding microRNAs (miRNAs) has
      been recognized in human cancer. In colorectal cancer, Autophagy plays critical
      roles in cancer progression as well as resistance to chemotherapy, and recent
      evidence demonstrates that miRNAs are directly involved in mediating these
      functions. In this review, we will focus on the recent advancements in the field
      of miRNA regulation of autophagy in colorectal cancer.

PMID- 28748219
TI  - Envy's pathology: Historical contexts.
AB  - This article is concerned with the physicality of envy primarily in early 
      modern, but also in eighteenth-century health contexts. The discussion brings
      together descriptions of the effects of envy on the body of the envier, mainly
      from works of physiology and health preservation, but also from literary and
      spiritual writings. These depictions of envy are studied beyond their symbolism
      and with a view to establish whether they are meaningful according to the medical
      theories of the time in which they occur. The discussion begins by acknowledging
      the status of envy as a 'disease' and looks to the specific ways in which the
      discourse of envy conveys this sense. I find that in the early modern discourse
      envy is always pathological, that is, it is experienced as disease and signifies
      disease in general and several diseases in particular. Moreover, envy is uniquely
      placed to convey pathology on account of its being connected to inherently
      pathogenic elements of the humoural theory. Specifically, envy is physiologically
      connected to melancholy, and the way it is presented comes close to attributes
      assigned to black bile. In addition, envy realizes pathology, the occurrence of
      disease in the body, by impairing the vital process of digestion and thus
      depriving the person from proper nourishment and sustenance. The analysis further
      considers how this impairment of the body fits with the physiological
      manifestation of envy as 'corrosion' and 'consumption'. Finding commonalities
      with other maladies mediated by these physiological signs the article concludes
      by considering the function of pathology in the conception of early modern envy.

PMID- 28748220
TI  - exampletestr-An easy start to unit testing R packages.
AB  - In spite of the utility of unit tests, most R package developers do not write
      them. exampletestr makes it easier to start writing unit tests by creating
      shells/skeletons of unit tests based on the examples in the user's package
      documentation. When completed, these unit tests test whether said examples run 
      correctly. By combining the functionality of exampletestr with that of covr,
      having ensured that their examples adequately demonstrate the features of their
      package, the developer can have much of the work of constructing a comprehensive
      set of unit tests done for them.

PMID- 28748221
TI  - RNA substrate length as an indicator of exosome interactions in vivo.
AB  - Background: The exosome complex plays key roles in RNA processing and degradation
      in Eukaryotes and Archaea. Outstanding structural studies identified multiple
      pathways for RNA substrates into the exosome in vitro, but identifying the
      pathway followed by individual RNA species in vivo remains challenging. Methods:
      We attempted to address this question using RNase protection. In vivo RNA-protein
      crosslinking (CRAC) was applied to the exosome component Rrp44/Dis3, which has
      both endonuclease and exonuclease activity. During CRAC, the exosome was purified
      under native conditions and subjected to RNase digestion, prior to protein
      denaturation and cDNA cloning. The resulting high-throughput sequence reads were
      stratified by length of the cDNA sequence. This should reflect RNA fragment
      lengths, and therefore the RNA region that was protected by exosome binding. We
      anticipated major read lengths of ~30nt and ~10nt, reflecting the "central
      channel" and "direct access" routes to the Rrp44 exonuclease active site observed
      in vitro. Results: Unexpectedly, no clear peak was observed at 30nt, whereas a
      broad peak was seen around 20nt. The expected ~10nt peak was seen, and showed
      strong elevation in strains lacking exonuclease activity. Unexpectedly, this peak
      was suppressed by point mutations in the Rrp44 endonuclease active site. This
      indicates that the short fragments are degraded by the exonuclease activity of
      Rrp44, but also suggests that at least some may be generated by endonuclease
      activity. Conclusions: The absence of 30nt protected fragments may reflect
      obligatory binding of cofactors at the entrance to the exosome central channel in
      vivo. The presence of ~20nt fragments apparently indicates an access route not
      yet reported from in vitro studies. Confident mapping of 10nt reads is
      challenging, but they are clearly derived from a subset of exosome targets. In
      particular, pre-rRNA species, which are major exosome targets, are strongly
      disfavored for the generation of short reads.

PMID- 28748222
TI  - An improved Plasmodium cynomolgi genome assembly reveals an unexpected
      methyltransferase gene expansion.
AB  - BACKGROUND: Plasmodium cynomolgi, a non-human primate malaria parasite species,
      has been an important model parasite since its discovery in 1907. Similarities in
      the biology of P. cynomolgi to the closely related, but less tractable, human
      malaria parasite P. vivax make it the model parasite of choice for liver biology
      and vaccine studies pertinent to P. vivax malaria. Molecular and genome-scale
      studies of P. cynomolgi have relied on the current reference genome sequence,
      which remains highly fragmented with 1,649 unassigned scaffolds and little
      representation of the subtelomeres.  Methods: Using long-read sequence data
      (Pacific Biosciences SMRT technology), we assembled and annotated a new reference
      genome sequence, PcyM, sourced from an Indian rhesus monkey. We compare the newly
      assembled genome sequence with those of several other Plasmodium species,
      including a re-annotated P. coatneyi assembly. RESULTS: The new PcyM genome
      assembly is of significantly higher quality than the existing reference,
      comprising only 56 pieces, no gaps and an improved average gene length. Detailed
      manual curation has ensured a comprehensive annotation of the genome with 6,632
      genes, nearly 1,000 more than previously attributed to P. cynomolgi. The new
      assembly also has an improved representation of the subtelomeric regions, which
      account for nearly 40% of the sequence. Within the subtelomeres, we identified
      more than 1300 Plasmodium interspersed repeat ( pir) genes, as well as a striking
      expansion of 36 methyltransferase pseudogenes that originated from a single copy
      on chromosome 9. CONCLUSIONS: The manually curated PcyM reference genome sequence
      is an important new resource for the malaria research community. The high quality
      and contiguity of the data have enabled the discovery of a novel expansion of
      methyltransferase in the subtelomeres, and illustrates the new comparative
      genomics capabilities that are being unlocked by complete reference genomes.

PMID- 28748223
TI  - PhenoPlasm: a database of disruption phenotypes for malaria parasite genes.
AB  - Two decades after the first Plasmodium transfection, attempts have been made to
      disrupt more than 3,151 genes in malaria parasites, across five Plasmodium
      species. While results from rodent malaria transfections have been curated and
      systematised, empowering large-scale analysis, phenotypic data from human malaria
      parasite transfections currently exists as individual reports scattered across a
      the literature. To facilitate systematic analysis of published experimental
      genetic data across Plasmodium species, we have built PhenoPlasm (
      http://www.phenoplasm.org), a database of phenotypes generated by transfection
      experiments in all Plasmodium parasites. The site provides a simple interface
      linking citation-backed Plasmodium reverse-genetic phenotypes to gene IDs. The
      database has been populated with phenotypic data on 367 P. falciparum genes,
      curated from 176 individual publications, as well as existing data on rodent
      Plasmodium species from RMgmDB and PlasmoGEM. This is the first time that all
      available data on P. falciparum transfection experiments has been brought
      together in a single place. These data are presented using ortholog mapping to
      allow a researcher interested in a gene in one species to see results across
      other Plasmodium species. The collaborative nature of the database enables any
      researcher to add new phenotypes as they are discovered. As an example of
      database utility, we use the currently available datasets to identify RAP (RNA
      binding domain abundant in Apicomplexa)-domain containing proteins as crucial to
      parasite survival.

PMID- 28748224
TI  - Utility of Genetic Testing for Confirmation of Abnormal Newborn Screening in
      Disorders of Long-Chain Fatty Acids: A Missed Case of Carnitine
      Palmitoyltransferase 1A (CPT1A) Deficiency.
AB  - An 18-month-old male was evaluated after presenting with disproportionately
      elevated liver transaminases in the setting of acute gastroenteritis. He had
      marked hepatomegaly on physical exam that was later confirmed with an abdominal
      ultrasound. Given this clinical picture, suspicion for a fatty acid oxidation
      disorder was raised. Further investigation revealed that his initial newborn
      screen was positive for carnitine palmitoyltransferase 1A (CPT1A) deficiency-a
      rare autosomal recessive disorder of long-chain fatty acid oxidation.
      Confirmatory biochemical testing in the newborn period showed carnitine levels to
      be unexpectedly low with a normal acylcarnitine profile. Thus, it was considered
      to be a false-positive newborn screen and metabolic follow-up was not
      recommended. Repeat biochemical testing during this hospitalization revealed a
      normal acylcarnitine profile. The only abnormalities noted were a low proportion
      of acylcarnitine species from plasma, an elevated free-to-total carnitine ratio,
      and mild hypoketotic medium chain dicarboxylic aciduria on urine organic acids.
      Gene sequencing of CPT1A revealed a novel homozygous splice site variant that
      confirmed his diagnosis. CPT1A deficiency has a population founder effect in the
      Inuit and other Arctic groups, but has not been previously reported in persons of
      Ashkenazi Jewish ancestry.

PMID- 28748225
TI  - Abnormal molecular response to Takayasu arteritis causing extensive large-vessel
      calcification.
AB  - Takayasu arteritis is a large-vessel vasculitis that often results in
      pulselessness due to fibrotic stenoses. Whereas minor calcification is sometimes
      seen with Takayasu arteritis, it rarely causes stenosis. Extensive calcification
      resulting in malperfusion is exceedingly rare and has been attributed to
      disorders in calcium trafficking in a chronic inflammatory state. We report an
      unusual case of rapidly progressive and extensive aortic calcification in the
      setting of Takayasu arteritis.

PMID- 28748226
TI  - Peripheral kynurenine-3-monooxygenase deficiency as a potential risk factor for
      metabolic syndrome in schizophrenia patients.
AB  - Increased predisposition of schizophrenia patients (SP) to development of obesity
      and insulin resistance suggested common signaling pathway between metabolic
      syndrome (MetS) and schizophrenia. Deficiency of kynurenine-3-monooxygenase
      (KMO), enzyme catalyzing formation of 3-hydroxykynurenine (3-HK) from kynurenine
      (Kyn), a tryptophan (Trp) metabolite, might contribute to development of MetS as
      suggested by non-expression of KMO genes in human fat tissue and elevated serum
      concentrations of Kyn and its metabolites, kynurenic (KYNA) and anthranilic (ANA)
      acids, in diabetic patients and Zucker fatty rats (ZFR). Markers of KMO
      deficiency: decreased 3-HK and elevated Kyn, KYNA and ANA, were observed in
      brains and spinal fluids of SP, and in brains and serum of experimental animals
      with genetically- or pharmacologically-induced KMO deficiency. However, elevated
      concentrations of ANA and decreased 3-HK were reported in serum of SP without
      concurrent increase of Kyn and KYNA. Present study aimed to re-assess serum Kyn
      metabolites (HPLC-MS) in a sub-group of SP with elevated KYNA. We found increased
      Kyn concentrations (by 30%) and Kyn:Trp ratio (by 20%) in serum of SP with
      elevated KYNA concentrations (by 40%). Obtained results and our previous data
      suggest that peripheral KMO deficiency might be manifested by, at least, two
      different patterns: elevated ANA with decreased 3-HK; and elevated KYNA and KYN.
      The latter pattern was previously described in type 2 diabetes patients and might
      underline increased predisposition of SP to development of MetS. Assessment of
      peripheral KMO deficiency might identify SP predisposed to MetS. Attenuation of
      the consequences of peripheral KMO deficiency might be a new target for
      prevention/treatment of obesity and diabetes in SP.

PMID- 28748227
TI  - Unsupervised Extraction of Diagnosis Codes from EMRs Using Knowledge-Based and
      Extractive Text Summarization Techniques.
AB  - Diagnosis codes are extracted from medical records for billing and reimbursement
      and for secondary uses such as quality control and cohort identification. In the
      US, these codes come from the standard terminology ICD-9-CM derived from the
      international classification of diseases (ICD). ICD-9 codes are generally
      extracted by trained human coders by reading all artifacts available in a
      patient's medical record following specific coding guidelines. To assist coders
      in this manual process, this paper proposes an unsupervised ensemble approach to
      automatically extract ICD-9 diagnosis codes from textual narratives included in
      electronic medical records (EMRs). Earlier attempts on automatic extraction
      focused on individual documents such as radiology reports and discharge
      summaries. Here we use a more realistic dataset and extract ICD-9 codes from EMRs
      of 1000 inpatient visits at the University of Kentucky Medical Center. Using
      named entity recognition (NER), graph-based concept-mapping of medical concepts,
      and extractive text summarization techniques, we achieve an example based average
      recall of 0.42 with average precision 0.47; compared with a baseline of using
      only NER, we notice a 12% improvement in recall with the graph-based approach and
      a 7% improvement in precision using the extractive text summarization approach.
      Although diagnosis codes are complex concepts often expressed in text with
      significant long range non-local dependencies, our present work shows the
      potential of unsupervised methods in extracting a portion of codes. As such, our
      findings are especially relevant for code extraction tasks where obtaining large
      amounts of training data is difficult.

PMID- 28748228
TI  - Supervised Extraction of Diagnosis Codes from EMRs: Role of Feature Selection,
      Data Selection, and Probabilistic Thresholding.
AB  - Extracting diagnosis codes from medical records is a complex task carried out by
      trained coders by reading all the documents associated with a patient's visit.
      With the popularity of electronic medical records (EMRs), computational
      approaches to code extraction have been proposed in the recent years. Machine
      learning approaches to multi-label text classification provide an important
      methodology in this task given each EMR can be associated with multiple codes. In
      this paper, we study the the role of feature selection, training data selection,
      and probabilistic threshold optimization in improving different multi-label
      classification approaches. We conduct experiments based on two different
      datasets: a recent gold standard dataset used for this task and a second larger
      and more complex EMR dataset we curated from the University of Kentucky Medical
      Center. While conventional approaches achieve results comparable to the state-of
      the-art on the gold standard dataset, on our complex in-house dataset, we show
      that feature selection, training data selection, and probabilistic thresholding
      provide significant gains in performance.

PMID- 28748229
TI  - Predicting Treatment Relations with Semantic Patterns over Biomedical Knowledge
      Graphs.
AB  - Identifying new potential treatment options (say, medications and procedures) for
      known medical conditions that cause human disease burden is a central task of
      biomedical research. Since all candidate drugs cannot be tested with animal and
      clinical trials, in vitro approaches are first attempted to identify promising
      candidates. Even before this step, due to recent advances, in silico or
      computational approaches are also being employed to identify viable treatment
      options. Generally, natural language processing (NLP) and machine learning are
      used to predict specific relations between any given pair of entities using the
      distant supervision approach. In this paper, we report preliminary results on
      predicting treatment relations between biomedical entities purely based on
      semantic patterns over biomedical knowledge graphs. As such, we refrain from
      explicitly using NLP, although the knowledge graphs themselves may be built from
      NLP extractions. Our intuition is fairly straightforward - entities that
      participate in a treatment relation may be connected using similar path patterns
      in biomedical knowledge graphs extracted from scientific literature. Using a
      dataset of treatment relation instances derived from the well known Unified
      Medical Language System (UMLS), we verify our intuition by employing graph path
      patterns from a well known knowledge graph as features in machine learned models.
      We achieve a high recall (92 %) but precision, however, decreases from 95% to an
      acceptable 71% as we go from uniform class distribution to a ten fold increase in
      negative instances. We also demonstrate models trained with patterns of length <=
      3 result in statistically significant gains in F-score over those trained with
      patterns of length <= 2. Our results show the potential of exploiting knowledge
      graphs for relation extraction and we believe this is the first effort to employ
      graph patterns as features for identifying biomedical relations.

PMID- 28748230
TI  - Diffusion Component Analysis: Unraveling Functional Topology in Biological
      Networks.

PMID- 28748232
TI  - Conservative vs Radical Approach for the Treatment of Solid/Multicystic
      Ameloblastoma: A Systematic Review and Meta-analysis of the Last Decade.
AB  - PURPOSE: To examine whether a difference exists in the relapse rate between the
      conservative and radical approaches after the treatment of solid/multicystic
      ameloblastoma (SMA), a systematic review of the literature based on evidence of
      the last decade was performed. MATERIALS AND METHODS: The search strategy
      incorporated examinations of electronic databases, supplemented by hand searches.
      A search of four electronic databases, including Ovid MEDLINE, PubMed, EMBASE and
      Web of Science, was carried out for relevant studies published in the English
      language from January 2005 to September 2015. Cross referencing and hand research
      was used to identify further articles. Relative Risk (RR) as effect estimates was
      calculated in both fixed and random effects models. RESULTS: Of 4234 abstracts
      screened, only 26 articles met the inclusion criteria and were screened in full
      text. Of these, only 4 were included in the final meta-analysis. CONCLUSION: The
      inverse of variance test revealed a statistical difference in the relapse rate
      for SMA treatment with the conservative vs radical approach. The higher
      recurrence rate after a conservative approach compared to the surgical approach
      is significant. However, this review cannot give any recommendation due to the
      lack of clinical evidence.

PMID- 28748231
TI  - The tongue display unit (TDU) for electrotactile spatiotemporal pattern
      presentation.
AB  - The Tongue Display Unit (TDU) is a 144-channel programmable pulse generator that
      delivers dc-balanced voltage pulses suitable for electrotactile
      (electrocutaneous) stimulation of the anterior-dorsal tongue, through a matrix of
      surface electrodes. This article reviews the theory of operation and a design
      overview of the TDU, as well as selected applications. These include sensory
      substitution, tactile information display and neurorehabilitation via induced
      neuroplasticity.

PMID- 28748233
TI  - Caries Prevalence and Risk Assessment in Thuringian Infants, Germany.
AB  - PURPOSE: To determine the caries prevalence and experience in Thuringian infants
      and to assess their caries risk. MATERIAL AND METHODS: The subjects were
      participants in a regional preventive programme, a birth cohort study with the
      aim of preventing caries. In the first year of life, children were invited to a
      dental examination at the Jena University Hospital. Dental caries was scored
      using WHO diagnostic criteria at the d1-level without radiography. Children were
      categorised as being of low, moderate or high risk for caries according to the
      caries-risk assessment tool of the American Academy of Pediatric Dentistry
      (AAPD). RESULTS: 512 children (mean age 6.7 +/- 2.2 months) were examined. 58.2%
      (n = 298) of all children had teeth (2.21 +/- 2.76). Caries prevalence of
      cavitated carious lesions was 1.7%, and prevalence of non-cavitated carious
      lesions was 7.7% in children who had teeth. Caries experience was 0.3 +/- 1.0 d1
      4mfs/0.2 +/- 1.5 d3-4mfs (range of 0 to 16). Children with caries were on average
      10.8 +/- 3.2 months old, while children without caries were 6.6 +/- 2.1 months.
      One hundred sixty-nine children (33.1%) were categorised at high risk for caries,
      and 98 already had teeth. CONCLUSION: Although caries prevalence and experience
      was relatively low in infants, one third of all children were categorised as
      being at high caries risk. Early dental visits are necessary to detect the first
      signs of caries, to assess the caries risk and to establish a dental home with a
      risk-related recall system. The caries-risk assessment tool (CAT) of the AAPD can
      assist the clinician in the decision-making process.

PMID- 28748234
TI  - Erosive Tooth Wear Among Different Tooth Types and Surfaces in Japanese Adults 15
      to 89 Years Old.
AB  - PURPOSE: To evaluate the prevalence of erosive tooth wear on buccal,
      incisal/occlusal and palatal/lingual surfaces in a wide age range of Japanese
      adults. MATERIALS AND METHODS: The study included a total of 1108 adults aged 15
      to 89 years in Tokyo, Japan. The subjects were asked to complete a self
      administered nutrition-related questionnaire. Two examiners evaluated tooth wear
      on the buccal, occlusal/incisal and palatal/lingual surfaces in a full-mouth
      recording, using a modified Smith and Knight tooth-wear index. Subjects who
      frequently consumed acidic beverages or food, or had gastric reflux and at least
      one tooth with an initial enamel smooth-surface wear facet were placed in an
      erosion-positive group, and the rest of subjects were placed in the erosion
      negative group. RESULTS: 26.1% of the participants were placed in the erosion
      positive group. For buccal surfaces, advanced wear progression was predominantly
      observed on maxillary and mandibular anterior teeth, especially in the youngest
      age group (15-39 years). On incisal/occlusal surfaces, early dentin exposure was
      observed in the middle age group (40-49 years) in the erosion-positive group. For
      palatal/lingual surfaces, wear progression was mainly observed on maxillary
      anterior teeth among 30- to 39-year olds and 50- to 59-year-old in the erosion
      positive group, but that prevalence was lower than for the other tooth surfaces.
      CONCLUSIONS: For all age groups of Japanese adults, the prevalence of erosive
      tooth wear depended on tooth types and surfaces.

PMID- 28748235
TI  - In Vitro Evaluation of the Effect of Chemical and Thermal Stress of the
      Mechanical Properties of Periodontal Curettes under Simulated Conditions of
      Sharpening Wear.
AB  - PURPOSE: To determine whether chemical and thermal stress as well as sharpening
      are aspects that must be considered to determine when a curette has become too
      weak to be used safely without the threat of breakage. MATERIALS AND METHODS: A
      total sample of 35 curette blades was divided into 2 principal groups, control
      (groups 1 to 3) and experimental (groups 4 to 6). The control group was divided
      into 3 colour-coded groups of 19 similar curette blades and was only subjected to
      progressive sharpening wear (not sterilised). The test group included 16 Gracey
      curette blades that were subjected to various degrees of progressive wear and
      different numbers of sterilisation cycles in 3 subgroups (subgroup 4 had 5
      sterilisation cycles; subgroup 5 had 30 cycles and experimental subgroup 6 had 55
      cycles). Using a universal testing machine, all blades were tested for strength
      until they fractured. RESULTS: No evidence was found that the simple presence or
      absence of sterilisation cycles produced a statistically significant difference
      between the two studied groups (sterilised and not sterilised). However, when
      comparing the six subgroups that underwent different numbers of sterilisation
      cycles, the analysis showed that the more sterilisation cycles a curette
      underwent, the more likely the curette was to fracture (p = 0.047). CONCLUSION:
      Sterilisation by itself does not produce a significant change in the fracture
      strength, whereas the number of sterilisation cycles clearly weakens the
      instrument. Sterilisation is a factor to control when evaluating the life of a
      periodontal curette for the patients' and professionals' safety.

PMID- 28748236
TI  - Locked nucleic acid (LNA) enhances binding affinity of triazole-linked DNA
      towards RNA.
AB  - Oligonucleotides containing internal triazole-3'-LNA linkages bind to
      complementary RNA with similar affinity and specificity to unmodified
      oligonucleotides, and significantly better than oligonucleotides containing
      triazole alone. In contrast LNA on the 5'-side of the triazole does not stabilise
      duplexes. Triazole-LNA confers great resistance towards enzymatic degradation
      relative to LNA alone.

PMID- 28748237
TI  - Total synthesis of (-)-kainic acid and (+)-allo-kainic acid through SmI2-mediated
      intramolecular coupling between allyl chloride and an alpha,beta-unsaturated
      ester.
AB  - A 3,4-disubstituted pyrrolidine ring was effectively cyclized through SmI2
      mediated reductive coupling between allyl chloride and an alpha,beta-unsaturated
      ester, although little has been reported about SmI2-promoted C-C bond formation
      of an allyl chloride with an alpha,beta-unsaturated ester. Selection of either
      the 3,4-cis- or 3,4-trans-selective cyclization can be accomplished simply by
      changing the additives from NiI2 to HMPA during reductive cyclization conducted
      in H2O-THF. Total synthesis of (-)-kainic acid and (+)-allo-kainic acid, which
      are pyrrolidine alkaloids used in neuroscience and neuropharmacology as useful
      molecular probes, was successfully achieved by using the stereo-complementary
      ring closure reactions promoted by SmI2 for the construction of the 2,3,4
      trisubsituted pyrrolidine scaffold of kainoids.

PMID- 28748238
TI  - Substantial enhancement of energy storage capability in polymer nanocomposites by
      encapsulation of BaTiO3 NWs with variable shell thickness.
AB  - Dielectric polymer nanocomposites have received keen interest due to their
      potential application in energy storage. Nevertheless, the large contrast in
      dielectric constant between the polymer and nanofillers usually results in a
      significant decrease of breakdown strength of the nanocomposites, which is
      unfavorable for enhancing energy storage capability. Herein, BaTiO3 nanowires
      (NWs) encapsulated by TiO2 shells of variable thickness were utilized to
      fabricate dielectric polymer nanocomposites. Compared with nanocomposites with
      bare BaTiO3 NWs, significantly enhanced energy storage capability was achieved
      for nanocomposites with TiO2 encapsulated BaTiO3 NWs. For instance, an ultrahigh
      energy density of 9.53 J cm-3 at 440 MV m-1 could be obtained for nanocomposites
      comprising core-shell structured nanowires, much higher than that of
      nanocomposites with 5 wt% raw ones (5.60 J cm-3 at 360 MV m-1). The discharged
      energy density of the proposed nanocomposites with 5 wt% mTiO2@BaTiO3-1 NWs at
      440 MV m-1 seems to rival or exceed those of some previously reported
      nanocomposites (mostly comprising core-shell structured nanofillers). More
      notably, this study revealed that the energy storage capability of the
      nanocomposites can be tailored by the TiO2 shell thickness. Finite element
      simulations were employed to analyze the electric field distribution in the
      nanocomposites. The enhanced energy storage capability should be mainly
      attributed to the smoother gradient of dielectric constant between the
      nanofillers and polymer matrix, which alleviated the electric field concentration
      and leakage current in the polymer matrix. The methods and results herein offer a
      feasible approach to construct high-energy-density polymer nanocomposites with
      core-shell structured nanowires.

PMID- 28748239
TI  - Phototoxicity of strained Ru(ii) complexes: is it the metal complex or the
      dissociating ligand?
AB  - A photochemically dissociating ligand in Ru(bpy)2(dmphen)Cl2 [bpy = 2,2'
      bipyridine; dmphen = 2,9-dimethyl-1,10-phenanthroline] was found to be more
      cytotoxic on the ML-2 Acute Myeloid Leukemia cell line than Ru(bpy)2(H2O)22+ and
      prototypical cisplatin. Our findings illustrate the potential potency of diimine
      ligands in photoactivatable Ru(ii) complexes.

PMID- 28748241
TI  - Spectral dependence of photoemission in multiphoton ionization of NO2 by
      femtosecond pulses in the 375-430 nm range.
AB  - We investigate the multiphoton ionization of NO2 using tunable (430-375 nm)
      femtosecond pulses and photoelectron-photoion coincidence momentum spectroscopy.
      In order to understand the complex electronic and nuclear photodynamics at play
      following absorption of three to five photons, we also report extended
      photoionization calculations using correlated targets and coupled channels.
      Exploring the multiphoton dissociative ionization (MPDI) and multiphoton
      ionization (MPI) processes over such a broad energy range enables us to lend
      further support to our work carried out around 400 nm of a femtosecond laser [S.
      Marggi Poullain et al., J. Phys. B: At., Mol. Opt. Phys., 2014, 47, 124024]. Two
      excitation energy regions are identified and discussed in terms of the proposed
      reaction pathways, highlighting the significant role of Rydberg states, such as
      the [R*(6a1)-1, 3psigma] Rydberg state, in the NO2 multiphoton excitation and
      photoionization. These new results support our previous assumption that different
      bent and linear geometries of the NO2+(X1Sigmag) ionic state contribute to the
      MPDI and MPI, consistent with the reported calculations which reveal an important
      vibronic coupling characterizing the photoemission. Remarkably, the strong
      anisotropy of the recoil frame photoelectron angular distribution (RFPAD)
      previously observed at 400 nm appears as a fingerprint across the whole explored
      photon energy range.

PMID- 28748244
TI  - A high performance and low-cost hole transporting layer for efficient and stable
      perovskite solar cells.
AB  - Here we report a small molecule oxidant 2,3,5,6-tetrafluoro-7,7,8,8-tetracyano
      quinodimethane (F4TCNQ) doped, low cost 2',7'-bis(bis(4
      methoxyphenyl)amino)spiro[cyclopenta[2,1-b:3,4-b']dithiophene-4,9'-fluorene]
      (FDT) hole transporting layer (HTL) for efficient mixed organic cation based
      MA0.6FA0.4PbI3 (MA = methyl ammonium, FA = formamidinium) perovskite solar cells
      (PSCs), fabricated via a highly reproducible controlled nucleation assisted
      restricted volume solvent annealing method, having full temperature compatibility
      with flexible substrates. The optimized (1 wt%) F4TCNQ doped FDT HTL based
      devices (F-FDT devices) demonstrate simultaneous enhancement of photovoltaic
      performance and device stability as well as significant reduction in photo
      current hysteresis, as compared to conventional bis(trifluoromethylsulfonyl)amine
      lithium (Li-TFSI) additive based FDT HTL devices (L-FDT devices). Adding to the
      merits, F-FDT PSCs exhibit about 75% higher device stability compared to
      conventional L-FDT devices during the course of three weeks. Mott-Schottky
      analysis and in-depth charge transport characterization were carried out using
      electrochemical impedance spectroscopy (EIS) of the fabricated devices to
      understand the superior performance of the F-FDT devices. In addition, detailed
      polaronic intensity characterization of the doped HTL films was performed via
      ultraviolet-visible near-infrared (UV-vis-NIR) spectroscopy to investigate the
      underlying mechanism. Mitigated photocurrent hysteresis in the F-FDT devices has
      also been examined in terms of the inherent electrode polarization phenomenon.
      Furthermore, the superior device stability of the F-FDT PSCs has been probed in
      terms of variation in electronic properties, surface wettability, crystallinity,
      and microstrain dislocation density, and a detailed picture of the underlying
      mechanism behind stability enhancement is presented.

PMID- 28748245
TI  - Monolayer germanium monochalcogenides (GeS/GeSe) as cathode catalysts in
      nonaqueous Li-O2 batteries.
AB  - The development of novel cathode catalysts is of great importance to the
      practical applications of nonaqueous lithium oxygen (Li-O2) batteries. Here by
      using first-principles calculations, we revealed the catalytic mechanism and
      evaluated the catalytic activity of monolayer germanium monochalcogenides (2D
      GeXs, X = S/Se) as cathode catalytic materials. For 2D-GeXs, Li4O4 with a ring
      like structure is the final discharge product. The free energy diagram
      demonstrates that 2D-GeSe is more energetically favorable than 2D-GeS due to its
      considerably lower oxygen reduction reaction (ORR) overpotential (0.94 V) and
      oxygen evolution reaction (OER) overpotential (1.30 V), which originate from its
      weaker binding with LiO2 and stronger binding with the inserted Li atom. The
      analyses on electronic properties elucidate that the final product of Li4O4 on 2D
      GeSe induces the semiconductor to semi-metal transition. Our results reflect that
      2D-GeSe is an excellent candidate as a cathode material in nonaqueous Li-O2
      batteries, while 2D-GeS is not appropriate.

PMID- 28748246
TI  - The mechanism of roughness-induced CO2 microbubble nucleation in polypropylene
      foaming.
AB  - Within the framework of classical density functional theory, the thermodynamic
      driving forces for CO2 microbubble nucleation have been quantitatively evaluated
      in the foaming of polypropylene containing amorphous and crystalline structures.
      After the addition of fluorinated polyhedral oligomeric silsesquioxane particles
      into the polypropylene matrix, we construct different composite surfaces with
      nanoscale roughness for bubble nucleation. Meanwhile, as the dissolved CO2
      molecules increase, the corresponding CO2/PP binary melts can be formulated in
      the systems. Due to the roughness effect coupled with the weak interactions of
      particle-PP, PP chains in the binary melts are depleted from the surfaces,
      leading to a significant enhancement of osmotic pressure in depletion regions.
      During the foaming process, a large number of dissolved CO2 molecules are
      squeezed into the regions, thus local supersaturations are dramatically improved,
      and the energy barriers for bubble nucleation are dramatically reduced. Moreover,
      when the nanocomposite surfaces display ordered nanoscale patterns, the energy
      barriers can be further reduced to their respective minimum values, and the
      bubble number densities reach their maximum. Accordingly, the bubble number
      densities can be enhanced by 4 or 5 orders of magnitude for bubbles nucleated on
      the crystalline or amorphous PP nanocomposite surface. In contrast, when the
      foaming pressure is increased from 15 to 20 MPa, the elevated bubble number
      density in the foaming PP matrix is less than one order of magnitude. As a
      result, the enhancement of local supersaturation induced by the controlled
      nanoscale roughness is much more effective than that of bulk supersaturation
      given by high pressure.

PMID- 28748247
TI  - Using non-empirically tuned range-separated functionals with simulated emission
      bands to model fluorescence lifetimes.
AB  - Fluorescence lifetimes were evaluated using TD-DFT under different approximations
      for the emitting molecule and various exchange-correlation functionals, such as
      B3LYP, BMK, CAM-B3LYP, LC-BLYP, M06, M06-2X, M11, PBE0, omegaB97, omegaB97X, LC
      BLYP*, and omegaB97X* where the range-separation parameters in the last two
      functionals were tuned in a non-empirical fashion. Changes in the optimised
      molecular geometries between the ground and electronically excited states were
      found to affect the quality of the calculated lifetimes significantly, while the
      inclusion of vibronic features led to further improvements over the assumption of
      a vertical electronic transition. The LC-BLYP* functional was found to return the
      most accurate fluorescence lifetimes with unsigned errors that are mostly within
      1.5 ns of experimental values.

PMID- 28748249
TI  - A triaxial tensile deformation-induced nanoporous structure of aluminium:
      estimation of surface area, solid volume, and dimensionless aspect ratio.
AB  - Nanoporous aluminium has great importance for large scale production of
      automobile and aerospace spare parts due to its lightweight and non-corrosive
      nature. It is also suitable for various packaging applications of edible things,
      electronic components, and medicines. We have used triaxial tensile deformation
      methodology to create a nanoporous structure of aluminium using molecular
      dynamics simulation. The surface area and solid volume have been calculated to
      characterize the 3-D nanoporous structure of aluminium. We have quantitatively
      characterized the growth and coalescences of the nanoporous structure via
      estimation of the number of nanopores, nanopore diameters, and dimensionless
      aspect-ratios (surface area to volume ratio). A high aspect ratio indicates a
      large number of tiny nanopores in the 3-D nanoporous structure of aluminium. We
      have found that crystalline aluminium (under ambient condition) significantly
      depicts a smaller aspect ratio as compared to amorphous aluminium during triaxial
      tensile deformation. We believe that the results of this study will provide new
      understanding to the researchers for the design and characterization of
      nanoporous metals.

PMID- 28748250
TI  - [Disseminated osteolytic lesions in a 28-year-old refugee].
AB  - A 28-year-old Syrian refugee presented with right-sided knee pain and progressive
      deterioration of the general condition over the past months. Laboratory
      diagnostics revealed severe hypercalcemia due to primary hyperparathyroidism, and
      computed tomography (CT) scanning demonstrated disseminated osteolytic lesions
      throughout the skeleton. Histologically, these lesions were characterized by
      multinuclear giant cells (defining these lesions as so-called brown tumors).
      Finally, surgical removal of a jugular mass allowed the histopathologic diagnosis
      of a sporadic parathyroid carcinoma. In the patient, this condition was
      associated with a mutation in the HPRT2 gene locus.

PMID- 28748251
TI  - Brexit: the country goes, but UK public health principles remain.

PMID- 28748252
TI  - 'MN1606SP' by 'Spencer' filial soybean population reveals novel quantitative
      trait loci and interactions among loci conditioning SDS resistance.
AB  - KEY MESSAGE: Four novel QTL and interactions among QTL were identified in this
      research, using as a parent line the most SDS-resistant genotype within soybean
      cultivars of the US early maturity groups. Soybean sudden death syndrome (SDS)
      reduces soybean yield in most of the growing areas of the world. The causal agent
      of SDS, soilborne fungus Fusarium virguliforme (Fv), releases phytotoxins taken
      up by the plant to produce chlorosis and necrosis in the leaves. Planting
      resistant cultivars is the most successful management practice to control the
      disease. The objective of this study was to identify quantitative trait loci
      (QTL) associated with the resistance response of MN1606SP to SDS. A mapping
      population of F 2:3 lines created by crossing the highly resistant cultivar
      'MN1606SP' and the susceptible cultivar 'Spencer' was phenotyped in the
      greenhouse at three different planting times, each with three replications.
      Plants were artificially inoculated using SDS infested sorghum homogeneously
      mixed with the soil. Data were collected on three disease criteria, foliar
      disease incidence (DI), foliar leaf scorch disease severity (DS), and root rot
      severity. Disease index (DX) was calculated as DI * DS. Ten QTL were identified
      for the different disease assessment criteria, three for DI, four for DX, and
      three for root rot severity. Three QTL identified for root rot severity and one
      QTL for disease incidence are considered novel, since no previous reports related
      to these QTL are available. Among QTL, two interactions were detected between
      four different QTL. The interactions suggest that resistance to SDS is not only
      dependent on additive gene effects. The novel QTL and the interactions observed
      in this study will be useful to soybean breeders for improvement of SDS
      resistance in soybean germplasm.

PMID- 28748253
TI  - Authors' reply to the comment by Hanis et al. on "Predictors of unsuccessful
      pessary fitting in women with prolapse: a cross-sectional study in general
      practice," by Panman et al.

PMID- 28748254
TI  - Comment on: Predictors of unsuccessful pessary fitting in women with prolapse: a
      cross-sectional study in general practice.

PMID- 28748255
TI  - Cellular and subcellular localization of ADP-ribosylation factor 6 in mouse
      peripheral tissues.
AB  - ADP-ribosylation factor 6 (Arf6) is a small GTPase that regulates endosomal
      trafficking and actin cytoskeleton remodeling. In the present study, we
      comprehensively examined the cellular and subcellular localization of Arf6 in
      adult mouse peripheral tissues by immunofluorescence and immunoelectron
      microscopy using the heat-induced antigen retrieval method with Tris-EDTA buffer
      (pH 9.0). Marked immunolabeling of Arf6 was observed particularly in epithelial
      cells of several tissues including the esophagus, stomach, small and large
      intestines, trachea, kidney, epididymis, oviduct, and uterus. In most epithelial
      cells of simple or pseudostratified epithelia, Arf6 exhibited predominant
      localization to the basolateral membrane and a subpopulation of endosomes. At an
      electron microscopic level, Arf6 was localized along the basolateral membrane,
      with dense accumulation at interdigitating processes and infoldings. Arf6 was
      present in a ring-like appearance at intercellular bridges in spermatogonia and
      spermatocytes in the testis and at the Flemming body of cytokinetic somatic cells
      in the ovarian follicle, thymus, and spleen. The present study provides
      anatomical clues to help understand the physiological roles of Arf6 at the whole
      animal level.

PMID- 28748256
TI  - Bioresorbable Vascular Scaffolds in Interventional Neuroradiology.
AB  - PURPOSE: Bioresorbable vascular scaffolds (BVS) have changed practice patterns in
      cardiology. These resorbable stents have not yet been utilized in the
      cerebrovascular circulation. We report the initial experiences with these devices
      in interventional neuroradiology. METHODS: A retrospective review of clinical
      presentations, imaging findings and follow-up results of all patients treated
      using a BVS by our neurovascular team was carried out using hospital electronic
      charts and the hospital radiographic archive system. Treatment was performed only
      if patients had a non-tortuous cerebrovascular anatomy suitable for navigation by
      the bulky BVS. RESULTS: In this study 9 patients (5 women, mean age 51.3 years)
      were treated with Absorb or DeSolve scaffolds without permanent morbidity or
      mortality, 5 had intracranial or vertebral artery stenosis and in 4 patients with
      cerebral aneurysms scaffold-assisted coiling was performed. At a mean follow-up
      of 22.3 months, 1 parent artery in the aneurysm group was occluded and the
      remaining BVSs showed no significant restenosis. Fusiform luminal enlargement was
      demonstrated in one aneurysm patient. In two patients treated for stenosis,
      transient intra-arterial filling defects resembling BVS struts (scaffold
      silhouette) was demonstrated on early follow-up angiograms. In the patient with
      parent artery occlusion (who was judged to have unjailed the internal carotid
      bifurcation) and in the patient with luminal remodeling, we were able to
      discontinue all antiplatelet medications at 3 years without any consequences.
      CONCLUSION: Absorbable stent technology has potential applications in
      interventional neuroradiology. We suggest that BVS should be optimized for
      cerebral circulation if prospective studies are to be undertaken for
      cerebrovascular applications of BVS.

PMID- 28748257
TI  - Use of Plant Preservative MixtureTM for establishing in vitro cultures from field
      plants: Experience with papaya reveals several PPMTM tolerant endophytic
      bacteria.
AB  - KEY MESSAGE: Prevalence of diverse PPMTM-tolerant endophytic bacteria in papaya,
      the broad-spectrum microbicide specified for use in plant tissue cultures,
      capable of surviving covertly in MS-based medium, with implications in
      contamination management. Plant Preservative MixtureTM was employed for
      establishing papaya (Carica papaya) tissue cultures from field explants.
      Comparing three recommended practices for controlling endogenous microbial
      contaminants, axillary shoot tips (1.0-1.5 cm) from cv. Arka Prabhath were
      treated with PPMTM 5% for 4 h (T1), 50% for 10 min (T2) or 100% for 10 min (T3)
      and cultured in MS-based papaya establishment medium (PEM). By 4-6 weeks, all
      treatments proved non-rewarding with cultures succumbing either to microbial
      contamination (80% in T1) or phytotoxicity effect/contamination (90% in T2 and
      95% in T3). Another trial adopting a multi-step surface sterilization treatment
      (carbendazim-cetrimide-HgCl2) followed by culturing in 0.05% PPM-supplemented PEM
      showed 35% obvious bacterial contamination compared with 40% in control. Single
      colonies from pooled bacterial growths were tested on 0.1% PPM-incorporated
      nutrient agar (NA) registering 60% isolates as PPM sensitive. Twenty PPM
      surviving isolates were selected and identified. This showed 85% Gram-positive
      bacteria including 80% under phylum Firmicutes (55% spore-forming Bacillaceae and
      25% Staphylococcaceae) and 5% Actinobacteria, and 15% Gram-negative
      Proteobacteria. About 50% isolates remained wholly non-obvious upon culturing on
      PEM while the rest showed slow growth with many displaying growth enhancement
      upon host tissue extract supplementation. Culturing the isolates on PPM
      supplemented NA indicated 90-95% as tolerating 0.05-0.1% PPM and 65% overriding
      0.2% PPM. The isolates, however, did not display obvious growth in PPM
      supplemented PEM where the spore formers survived. The results indicate the
      prevalence of diverse PPMTM-tolerant endophytic bacteria in papaya most of which
      survive covertly in MS-based medium and the need for taking this into account
      while using PPMTM for contamination management.

PMID- 28748258
TI  - EZH2 is involved in silencing of WNT5A during epithelial-mesenchymal transition
      of colon cancer cell line.
AB  - PURPOSE: Transforming growth factor-beta (TGF-beta) induction of epithelial
      mesenchymal transition (EMT) in SW480 was established as a system for studies of
      colon cancer metastasis. However, the epigenetic mechanisms underlying this
      process remain unknown. In mammal, polycomb repressive complex-2 (PRC2) is a
      highly conserved histone methyltransferase involved in epigenetic regulations.
      Enhancer of zeste Homolog 2 (EZH2) is the catalytic subunit of PRC2, which
      catalyzes methylation of lysine 27 of histone H3 (H3K27). METHODS: An inducible
      EMT system in colorectal cancer was utilized to study its mechanistic and
      phenotypic changes. Particularly, gene expression analysis was studied after
      immunoprecipitation. RESULTS: In this study, we reported that EZH2 is
      significantly enriched in the promoter region of WNT5A after TGF-beta induction
      in SW480 colon cancer cell line, which in turn silenced the expression of WNT5A.
      Furthermore, EZH2 inhibitor antagonized the TGF-beta-induced morphological
      conversion associated with epithelial-mesenchymal transition (EMT). Conversely,
      inhibition of histone H3K27me3 reader CBX does not affect the WNT5A expression
      level during TGF-beta-induced EMT. CONCLUSIONS: Our results indicate that EZH2
      was essential for the silencing of WNT5A during TGF-beta-induced epithelial
      mesenchymal transition of colon cancer cells.

PMID- 28748259
TI  - Primary nasopharyngeal polyps: a case series on a rare clinical entity.
AB  - Primary non-neoplastic polyps originating from the nasopharynx have not been
      reported in the English language literature. We present the clinical and
      histopathological features of three primary nasopharyngeal polyps. Clinical data
      of three patients with primary nasopharyngeal polyps treated at the Department of
      Otolaryngology, The First Affiliated Hospital of Sun Yat-sen University between
      2005 and 2015 were analyzed and presented. Three male patients from 45 to 63
      years presented with nasopharyngeal masses. CT or MRI examination showed
      nasopharyngeal space-occupying lesions. Two patients were initially diagnosed
      with nasopharyngeal angiofibroma and one patient with nasopharyngeal carcinoma.
      After surgical excision, based on the histological examination, the tissue masses
      were all diagnosed as inflammatory polyps. Histologically, the polyps
      demonstrated significant oedema, collagen deposition, leukocytic infiltration,
      and epithelial remodelling. Primary nasopharyngeal polyps represent a distinct
      clinical entity and should be considered in the differential diagnosis of
      nasopharyngeal masses.

PMID- 28748260
TI  - Clinical predictors for reactive tube feeding in patients with advanced
      oropharynx cancer receiving radiotherapy +/- chemotherapy.
AB  - Enteral feeding is often required for nutrition support in head and neck cancer
      patients when oral intake is inadequate. When to initiate the insertion of a
      feeding tube continues to be a debated issue in our institution. We investigated
      the use of reactive feeding tubes (RFTs) in patients with advanced stage
      oropharynx cancer (OPC). Data were retrospectively collected on 131 patients who
      had radiotherapy (RT) +/- chemotherapy from 2005 to 2015. Predictors for RFT
      insertion were investigated. Weight loss during RT was compared between those
      with RFT versus prophylactic tubes (PFTs) versus no tube, and survival outcomes
      evaluated. RFTs were more likely to be needed in patients who had bilateral neck
      node irradiation (p = 0.001) and concurrent chemoradiotherapy (CRT) (p = 0.038).
      Patients with RFTs had significantly higher mean percentage weight loss during RT
      (9.5 +/- 3.4%) (p < 0.001) when compared to those with a PFT (5.2 +/- 4.7%) and
      those with no tube (5.4 +/- 3.1%). No difference was seen in 5-year survival
      rates in patients who did not have a feeding tube to those who required a RFT.
      RFT use is frequent in OPC, although difficult to predict. CRT and bilateral neck
      node irradiation were found to be associated with the need for the insertion of a
      feeding tube during RT. These patients also experience significantly higher
      weight loss, therefore, prophylactic tubes may need to be considered more often
      in this population.

PMID- 28748261
TI  - Long-term functional outcomes after resection of tongue cancer: determining the
      optimal reconstruction method.
AB  - The appropriate tongue reconstruction method is critical for better functional
      outcomes. The aim of this study was to determine the optimal reconstructive
      method for restoring postoperative function based on the extent of resection. We
      retrospectively reviewed 43 patients with lateral oral tongue cancer who
      underwent glossectomy between January 2010 and October 2014. Tongue mobility,
      articulation, verbal diadochokinesis, speech intelligibility and swallowing
      outcomes were assessed 2-3 years postoperative and were analyzed according to
      resected tongue volume and the method of reconstruction. In partial glossectomy
      cases, the secondary intention group had better function in tongue mobility,
      articulation, and speech intelligibility (p < 0.001 for all) than the free flap
      reconstruction group. In contrast, in hemi-glossectomy cases, the free flap
      reconstruction group had better tongue mobility, articulation, verbal
      diadochokinesis and speech intelligibility (p < 0.05 for all) than the secondary
      intention group. There was no significant difference in swallowing outcome
      between the secondary intention and flap reconstruction groups in both partial
      glossectomy and hemi-glossectomy cases. In conclusion, secondary intention
      appears to be the most appropriate option after partial glossectomy. However,
      flap reconstruction is necessary to restore tongue volume and function in
      patients who undergo a resection of more than half of the tongue volume.

PMID- 28748262
TI  - Erratum to: Notomelia and related neural tube defects in a baby born in Niger:
      case report and literature review.

PMID- 28748263
TI  - Cerebral palsy and Adeli method: is it worth a try?

PMID- 28748264
TI  - [Zoledronate-induced panuveitis].
AB  - Zoledronate-induced (Aclasta(r)) uveitis is a rare iatrogen-induced inflammation
      of ocular structures, which can result in substantial morphological and
      functional limitations. This case report describes the clinical course of a
      female patient with zoledronate-induced panuveitis. Additionally, the diagnostic
      procedure, therapy and follow-up are presented.

PMID- 28748265
TI  - Epidemiology of heart failure in Germany: a retrospective database study.
AB  - BACKGROUND: Chronic heart failure (HF) is associated with significant healthcare
      expenditure, morbidity, and mortality. This study investigated the epidemiology
      of HF in Germany. METHODS: This retrospective study used anonymous healthcare
      claims data from the German Health Risk Institute on individuals with statutory
      health insurance. Patients with uninterrupted data from 1 January 2009 to 31
      December 2013 or death (whichever occurred first), and >=2 recorded HF-related
      diagnoses in 2011, were included. Patients with newly diagnosed HF were
      identified. Patients were followed up for 2 years from first diagnosis. RESULTS:
      Of 3,132,337 eligible patients, 123,925 (55.0% women; mean age 76.2 years) had
      HF: a prevalence of 3.96%. Of these, 26,368 had newly diagnosed HF: an incidence
      of 655/100,000 persons at risk. Incidence increased with age and was similar
      regardless of sex. During follow-up, there were 48,159 hospital admissions among
      newly diagnosed patients (1.8 hospitalizations/patient/2 years); HF accounted for
      6% of these. Additionally, 20,148 patients (16.3%) overall and 5983 newly
      diagnosed patients (22.7%) died. Most new cases of HF were diagnosed by office
      based physicians (63.2%); new cases among hospital inpatients were predominantly
      diagnosed by internal medicine specialists (70.7%). Overall, 94.0% received their
      initial prescription for HF treatment from a family practitioner. CONCLUSIONS:
      The high prevalence and incidence observed in this representative sample
      emphasize the burden of HF in Germany. Substantial hospitalization rates and
      mortality highlight the need for early diagnosis and appropriate treatment, and
      for close cooperation between physician specialties and healthcare sectors.

PMID- 28748266
TI  - Treatment of chronic heart failure in Germany: a retrospective database study.
AB  - BACKGROUND: Adherence to treatment guidelines affects outcomes in patients with
      chronic heart failure (HF). We investigated patient pathways and treatment
      patterns for HF in Germany. METHODS: This retrospective study used anonymous
      healthcare claims data from the German Health Risk Institute on individuals with
      statutory health insurance. Patients with uninterrupted data from 1 January 2009
      to 31 December 2013 or death (whichever occurred first), and >=2 recorded HF
      related diagnoses in 2011, were included. Patients with newly diagnosed HF were
      identified. Use of treatment patterns recommended by the European Society of
      Cardiology (2008) and German Nationale VersorgungsLeitlinien (2011) guidelines
      was evaluated. RESULTS: Of 123,925 patients with HF, 21.3% were newly diagnosed.
      Overall, 63.2% of new HF diagnoses were made in the ambulatory setting; 61.6% of
      these were made by family practitioners and 14.8% by cardiologists. In the
      ambulatory setting, family practitioners were primarily responsible for
      treatment; specialists in internal medicine (70.3% cardiologists) were mainly
      responsible for performing HF-related technical diagnostics. One-fifth (20.9%) of
      patients received a New York Heart Association (NYHA) classification; 45.1% of
      these received a guideline-based treatment pattern. Application of the
      recommended treatment pattern decreased with advancing disease severity (NYHA
      class IV: 21.1% application) and older age (>=90 years: 28.3% application).
      CONCLUSIONS: Family practitioners play a key role in the diagnosis and initial
      treatment of HF in Germany. A substantial proportion of patients do not receive
      guideline-recommended pharmacotherapy. These findings should be reflected in the
      planning of national disease management programmes.

PMID- 28748267
TI  - [Sex education and prevention of sexual violence : Contributions to a
      differential-sensitive prevention of sexualised violence].
AB  - Prevention of sexual violence against children and adolescents obtains high
      priority in educational contexts. This is due to the massive (possible)
      psychosocial impacts of sexual victimization as well as to the considerable
      prevalence rates that are reported in current studies. Preventive approaches are
      predominantly native to violence prevention and sex education where they are
      characterized by independent lines of tradition and positions. This contribution
      outlines their empirically largely unexplained relation with a focus on the
      history and development of the discourses of sex education. Diverging
      disciplinary attempts of positioning towards the prevention of sexual violence
      reveal an area of conflict between sex-positive and preventive educational
      objectives. A primacy of preventive contents is seen to be threatening a
      comprehensive sex education that emphasizes the positive aspects of sexuality. On
      the other hand, its standards are opposed to excluding and to tabooing sexual
      violence as a topic. Yet unfinished is therefore the search for a "third way"
      that might transfer the opposites of both approaches into integrative educational
      concepts. Unsettled questions about possible contributions of sex education to
      the prevention of sexual violence, and especially to which extent they are
      sensitive to difference are discussed based on international research and the
      theory of sex education.

PMID- 28748268
TI  - [Sexual dysfunction: Changing conceptions and criteria of classification].
AB  - BACKGROUND: Sexual response is the result of a complex interaction of
      psychological, physiological, interpersonal, social and cultural factors. Those
      factors - as well as sexual behavior - are subject to permanent change.
      OBJECTIVES: In this study, we investigated how the growth of basic knowledge and
      constantly changing social-cultural conditions impact the scientific definition
      of sexual dysfunctions, which controversies exist and to what degree these
      changes counteract the common tendencies of medicalization and stigmatization of
      sexual difficulties. MATERIALS AND METHODS: With reference to the leading
      international classification systems of mental disorders and on the basis of the
      current scientific literature, we comment and reflect the changed criteria of
      sexual dysfunctions in women and men. RESULTS AND CONCLUSIONS: The new revised
      criteria for sexual dysfunctions are more objective, which provides an enhanced
      basis for valid diagnoses. The concept of sexual aversion is considered obsolete
      and no longer being pursued. Nevertheless, there are obvious differences between
      the revised classification systems, especially regarding the dualistic
      perspective of sexual problems as either caused by psychological versus organic
      factors. Further change is predetermined.

PMID- 28748269
TI  - Presence of BPIFB1 in saliva from non-obese diabetic mice.
AB  - We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial
      protein in the palate, lung, and nasal epithelium clone protein family, was
      increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice,
      which is an animal model for Sjogren's syndrome. However, we did not previously
      assess the protein levels. In this report, we confirmed the expression of BPIFB1
      protein in the parotid glands of NOD mice. Immunoblotting of subcellular
      fractions revealed that BPIBB1 was localised in secretory granules in parotid
      glands from NOD mice, and was almost not in parotid glands from the control mice.
      BPIFB1 had N-linked glycan that reacted with Aleuria aurantia lectin, which
      caused two types of spots with a slightly different pI and molecular weight. The
      expression of BPIFB1 protein was also demonstrated by immunohistochemistry.
      BPIFB1 was detected in the saliva from NOD mice but not in the saliva from the
      control mice, indicating individual constitution. BPIFB1 in saliva may be applied
      to other research as a diagnostic marker.

PMID- 28748270
TI  - Color difference of composite resins after cementation with different shades of
      resin luting cement.
AB  - The purpose of this study was to evaluate the color difference of nanohybrid and
      ormocer-based composite resins with different thicknesses when 4 different shades
      of resin luting cement were used. 56 disc specimens of each composite resin
      (Aelite aesthetic enamel, Ceram-X mono) with 0.5 and 1 mm thicknesses were
      fabricated. Baseline color measurements were performed using a clinical
      spectrophotometer. The specimens of each thicknesses of each resin were randomly
      divided into 4 groups according to the shades of resin luting cement (white/A1,
      yellow/universal/A3, transparent and white opaque) (n = 7). Mixed resin cement
      was applied onto the resin specimens using a Teflon mold in 0.1 mm thickness.
      Color measurements of cemented composite resin specimens were repeated and color
      difference (?E) between baseline and after cementation measurements was
      calculated. ANOVA and Tukey's test were used for statistical analysis. The opaque
      shade had significantly increased ?E values as compared to the other shades (p <
      0.05). For all shades except white opaque in both thicknesses, ?E values of
      aelite aesthetic enamel were higher as compared to Ceram-X mono. There is no
      significant difference between 2 thicknesses for both resins in terms of ?E
      values. The shade of resin cement and the type of the resin affected the final
      color; however, the thickness of composite resin had no influence on the final
      color of restoration. Selecting the shade of resin luting cement before
      cementation of indirect composite laminate restoration is important to achieve
      final color match.

PMID- 28748271
TI  - The emerging role of gamma knife radiosurgery in the management of
      glossopharyngeal neuralgia.
AB  - Glossopharyngeal neuralgia (GPN) represents a rare craniofacial disorder
      accounting for about 1% of all craniofacial pain syndromes. GPN shares several
      pathophysiologic and clinical features with the more common trigeminal neuralgia.
      Medical therapy and microvascular decompression, in case of vascular nerve
      compression, represented the mainstay of GPN management. Other ablative therapies
      have been reported to date; however, few data are available because of the rarity
      of this pain syndrome. Among the ablative procedures, gamma knife radiosurgery
      (GKRS) has been recently introduced in the management of GPN with good pain
      control and low complication rates. Authors performed a systematic review of the
      published literature about GKRS in the management of GPN. Radiosurgical treatment
      data, pain control and recurrence rate have been analysed and compared. GKRS
      represented a valuable and effective treatment option for the management of GPN.
      Pain control and complication rates are better than those reported by other
      ablative procedures and microvascular decompression; however, future studies
      should be focused on the long-term efficacy of GKRS.

PMID- 28748272
TI  - A Small Cellulose-Binding-Domain Protein (CBD1) in Phytophthora is Highly
      Variable in the Non-binding Amino Terminus.
AB  - The small cellulose-binding-domain protein CBD1 is tightly bound to the
      cellulosic cell wall of the plant pathogenic stramenopile Phytophthora infestans.
      Transgene expression of the protein in potato plants also demonstrated binding to
      plant cell walls. A study was undertaken using 47 isolates of P. infestans from a
      worldwide collection, along with 17 other Phytophthora species and a related
      pathogen Plasmopara halstedii, to determine if the critical cell wall protein is
      subject to amino acid variability. Within the amino acid sequence of the secreted
      portion of CBD 1, encoded by the P. infestans isolates, 30 were identical with
      each other, and with P. mirabilis. Four isolates had one amino acid difference,
      each in a different location, while one isolate had two amino acid substitutions.
      The remaining 13 isolates had five amino acid changes that were each in identical
      locations (D17/G, D31/G, I32/S, T43/A, and G50/A), suggesting a single origin.
      Comparison of P. infestans CBD1 with other Phytophthora species identified
      extensive amino acid variation among the 60 amino acids at the amino terminus of
      the protein, and a high level of conservation from G61, where the critical
      cellulose-binding domain sequences begin, to the end of the protein (L110). While
      the region needed to bind to cellulose is conserved, the region that is available
      to interact with other cell wall components is subject to considerable variation,
      a feature that is evident even in the related genus Plasmopara. Specific changes
      can be used in determining intra- and inter-species relatedness. Application of
      this information allowed for the design of species-specific primers for PCR
      detection of P. infestans and P. sojae, by combining primers from the highly
      conserved and variable regions of the CBD1 gene.

PMID- 28748273
TI  - Changes in the Intestinal Microbiota of Gibel Carp (Carassius gibelio) Associated
      with Cyprinid herpesvirus 2 (CyHV-2) Infection.
AB  - Gut microbiota are integral to the host, and have received increased attention in
      recent years. However, information regarding the intestinal microbiota of many
      aquaculture animals is insufficient; elucidating the dynamics of the intestinal
      microbiota can be beneficial for nutrition, immunity, and disease control. In
      this study, we used 16S rRNA sequencing to observe changes in the intestinal
      microbiota of gibel carp (Carassius auratus gibelio) associated with cyprinid
      herpesvirus 2 (CyHV-2) infection. Our results indicate that the diversity of the
      intestinal microbiota was strongly reduced, and the composition was dramatically
      altered following CyHV-2 infection. The most dominant species in healthy fish
      were Cetobacterium, Rhodobacter, and Crenothrix; meanwhile, Cetobacterium,
      Plesiomonas, Bacteroides, and Flavobacterium were the most abundant species in
      sick fish. Plesiomonas was highly abundant in infected samples, and could be used
      as a microbial biomarker for CyHV-2 infection. Chemical properties of the
      aquaculture water were significantly correlated with the microbial community
      structure; however, it is difficult to determine whether these changes are a
      cause or consequence of infection. However, it may be possible to use probiotics
      or prebiotics to restore the richness of the host intestinal microbiota in
      infected animals to maintain host health.

PMID- 28748275
TI  - Head trauma and Parkinson's disease: results from an Italian case-control study.
AB  - We evaluated the possible association between head trauma and Parkinson's disease
      (PD). The FRAGAMP (Fattori di Rischio Ambientali e Genetici Associati alla
      Malattia di Parkinson) study is a large Italian multicenter case-control study
      carried out to evaluate the possible role of environmental and genetic factors in
      PD. Cases and controls were enrolled from six movement disorders centers located
      in the Central-Southern Italy. A standardized questionnaire was administered to
      record demographic, epidemiological, and clinical data. Positive history of head
      trauma was considered only if the head trauma preceded the onset of PD. All cases
      and controls underwent a standard neurological examination. Adjusted ORs and 95%
      CI were estimated using multivariate analysis (logistic regression). Four hundred
      ninety-two PD patients (292 men and 200 women) and 459 controls (160 men and 299
      women) were enrolled in the study. A positive history for head trauma was
      reported by 106 (21.5%) PD patients and by 62 (13.5%) healthy controls.
      Multivariate analysis (OR adjusted by age, sex, family history, coffee smoking,
      and alcohol consumption) showed a significant positive association between PD and
      head trauma with an adjusted OR of 1.50 (95%CI 1.04-2.17; p value 0.03). In
      agreement with literature data, our study supports the positive association
      between head trauma and PD.

PMID- 28748276
TI  - Resuming the obsolete term "small head": when microcephaly occurs without
      cognitive impairment.
AB  - Microcephaly is defined as a head circumference measurement of 2 or 3 standard
      deviations below the mean for age and sex. However, distinguishing the value of 
      2 or -3 standard deviations as a cutoff is relevant in the clinical practice,
      since the limit of -3 standard deviations is more frequently associated with
      cognitive impairment. The use of ultrasound scans in pregnancy has allowed the
      identification of subjects with a measurement of the head circumference at the
      limit of the cutoff for gestational age, but who do not subsequently show
      cognitive delay. The same is true for newborns with a -2 to -3 standard
      deviations cutoff, and without anomalous clinical signs, for which a cognitive
      delay is not easily diagnosed. In this case, to define an infant as being
      affected by microcephaly (with a prognosis usually recognized as harmful) may be
      unnecessarily distressful for parents or caregivers. In the cases mentioned,
      resuming the word "small head" instead of microcephaly to define such subjects
      could be more appropriate and more appreciated.

PMID- 28748277
TI  - Kribbella sindirgiensis sp. nov. isolated from soil.
AB  - A Kribbella strain FSN23T was isolated from soil sample which was collected from
      Caygoren Dam lakeside located in Sindirgi, Turkey. The isolate was investigated
      using a polyphasic approach consisting of numeric, chemotaxonomic and molecular
      analysis. The isolate indicated chemotaxonomic, morphological and phylogenetic
      properties associated with members of the genus Kribbella. Phylogenetic analysis
      based on the 16S rRNA sequence of the strain demonstrated that the strain forms a
      subclade with K. aluminosa HKI 0478T and K. jejuensis HD9T. The organism formed
      an extensively branched substrate and aerial hyphae which generated spiral chains
      of spores with smooth surfaces. The cell wall contained LL-diaminopimelic acid,
      and the whole cell sugars were glucose and ribose along with trace amounts of
      mannose. The polar lipids were identified as phosphatidylglycerol,
      diphosphatidylglycerol, four unidentified lipids and five unidentified polar
      lipids. The predominant menaquinone was MK-9(H4). The major cellular fatty acids
      were anteiso-C15:0 and iso-C16:0. Polyphasic taxonomy properties confirm that
      strain FSN23T represents a novel Kribbella taxon distinguished from closely
      related type strains. Hence, strain FSN23T (=KCTC 29220T = DSM 27082T) is
      proposed as the type strain of a novel species with the name Kribbella
      sindirgiensis sp. nov.

PMID- 28748278
TI  - [Therapy escalation for the potential organ donor : Are all intensive care
      measures also ethically justifiable?]
AB  - The gap between the number of organs needed and the number available has
      dramatically increased in Germany in the last decade-for intensivists and
      transplantation specialists, it is challenging to cover the demand responsibly.
      It is therefore increasingly important to identify potential organ donors in
      order to realize organ donation. An escalation of intensive care measures is
      often required, which raises critical ethical questions. In Germany, organ
      donation is only allowed after brain death with prior informed consent from the
      deceased or his/her relatives. Determining the willingness of the potential organ
      donor and adapting the subsequent intensive care to it requires experience and
      empathy. Therapy escalation for the realization of organ donation is not opposed
      to the basic ethical principles of medicine, but remains an individual decision.
      A time limitation of this last intensive therapy phase to achieve optimal
      conditions for transplantation should be discussed with the relatives and adapted
      to the medical requirements. This article would like to highlight ethical
      questions that are relevant in the context of therapy escalation of potential
      organ donors and, thus, support the decision-making process.

PMID- 28748279
TI  - [Invasive Candida infections in liver cirrhosis].

PMID- 28748280
TI  - [Prognostic importance of bystander efforts in out-of-hospital cardiac arrest].

PMID- 28748281
TI  - Electric-field-induced spin switch of endohedral dodecahedrane heterodimers
      H@C20Hn-C20Hn@M (M= Cu, Ag and Au, n = 15, 18, and 19): a theoretical study.
AB  - We designed nine endohedral dodecahedrane heterodimers H@C20Hn-C20Hn@M (M = Cu,
      Ag, and Au, n = 15, 18, and 19) that may act as single-molecule spin switches,
      and we predicted theoretically that the ground states of the dimmers shift from
      low-spin states (S = 0) to the high-spin states (S = 1) under an external
      electric field applied parallel or perpendicular to the molecular symmetry axes,
      consisting well with the analyses of Stark effect. Molecular orbitals analyses
      provide an intuitive insight into the spin crossover behavior. This study expands
      the application of endohedral chemistry and provides new molecules for designing
      single-molecule spin switch.

PMID- 28748282
TI  - Electronic fine structure calculation of metal complexes with three-open-shell s,
      d, and p configurations.
AB  - The ligand field density functional theory (LFDFT) algorithm is extended to treat
      the electronic structure and properties of systems with three-open-shell electron
      configurations, exemplified in this work by the calculation of the core and semi
      core 1s, 2s, and 3s one-electron excitations in compounds containing transition
      metal ions. The work presents a model to non-empirically resolve the multiplet
      energy levels arising from the three-open-shell systems of non-equivalent ns, 3d,
      and 4p electrons and to calculate the oscillator strengths corresponding to the
      electric-dipole 3d m  -> ns 13d m 4p 1 transitions, with n = 1, 2, 3 and m = 0,
      1, 2, ..., 10 involved in the s electron excitation process. Using the concept of
      ligand field, the Slater-Condon integrals, the spin-orbit coupling constants, and
      the parameters of the ligand field potential are determined from density
      functional theory (DFT). Therefore, a theoretical procedure using LFDFT is
      established illustrating the spectroscopic details at the atomic scale that can
      be valuable in the analysis and characterization of the electronic spectra
      obtained from X-ray absorption fine structure or electron energy loss
      spectroscopies.

PMID- 28748283
TI  - Modification of 56ACARBO force field for molecular dynamic calculations of
      chitosan and its derivatives.
AB  - The GROMOS 56ACARBO force field for the description of carbohydrates was modified
      for calculations of chitosan (poly-1,4-(N-acetyl)-beta-D-glucopyranosamine-2)
      with protonated and non-protonated amino groups and its derivatives. Additional
      parameterization was developed on the basis of quantum chemical calculations. The
      modified force field (56ACARBO_CHT) allows performing the molecular dynamic
      calculations of chitosans with different degrees of protonation corresponding to
      various acidity of medium. Test calculations of the conformational transitions in
      the chitosan rings and polymeric chains as well as the chitosan nanocrystal
      dissolution demonstrate good agreement with experimental data. Graphical abstract
      The GROMOS 56ACARBO_CHT force field allows performing the molecular dynamic
      calculations of chitosans with different types of amio-group: free, protonated,
      substituted.

PMID- 28748284
TI  - A density functional theory study on the hydrogen bonding interactions between
      luteolin and ethanol.
AB  - Ethanol is one of the most commonly used solvents to extract flavonoids from
      propolis. Hydrogen bonding interactions play an important role in the properties
      of liquid system. The main objective of the work is to study the hydrogen bonding
      interactions between flavonoid and ethanol. Luteolin is a very common flavonoid
      that has been found in different geographical and botanical propolis. In this
      work, it was selected as the representative flavonoid to do detailed research.
      The study was performed from a theoretical perspective using density functional
      theory (DFT) method. After careful optimization, there exist nine optimized
      geometries for the luteolin - CH3CH2OH complex. The binding distance of X -
      H...O, and the bond length, vibrational frequency, and electron density changes
      of X - H all indicate the formation of the hydrogen bond in the optimized
      geometries. In the optimized geometries, it is found that: (1) except for the
      H2', H5', and H6', CH3CH2OH has formed hydrogen bonds with all the hydrogen and
      oxygen atoms in luteolin. The hydrogen atoms in the hydroxyl groups of luteolin
      form the strongest hydrogen bonds with CH3CH2OH; (2) all of the hydrogen bonds
      are closed-shell interactions; (3) the strongest hydrogen bond is the O3' -
      H3'...O in structure A, while the weakest one is the C3 - H3...O in structure E;
      (4) the hydrogen bonds of O3' - H3'...O, O - H...O4, O - H...O3' and O - H...O7
      are medium strength and covalent dominant in nature. While the other hydrogen
      bonds are weak strength and possess a dominant character of the electrostatic
      interactions in nature.

PMID- 28748286
TI  - Normalized levels of red blood cells expressing phosphatidylserine, their
      microparticles, and activated platelets in young patients with beta-thalassemia
      following bone marrow transplantation.
AB  - Bone marrow transplantation (BMT) serves as the only curative treatment for
      patients with beta-thalassemia major; however, hemostatic changes have been
      observed in these BMT patients. Aggregability of thalassemic red blood cells
      (RBCs) and increased red blood cell-derived microparticles (RMPs) expressing
      phosphatidylserine (PS) are thought to participate in thromboembolic events by
      initially triggering platelet activation. To our knowledge, there has been no
      report providing quantitation of these circulating PS-expressing RBCs and RMPs in
      young beta-thalassemia patients after BMT. Whole blood from each subject was
      fluorescently labeled to detect RBC markers (CD235a) and annexin-V together with
      the known number TruCountTM beads. PS-expressing RBCs, RMPs, and activated
      platelets were identified by flow cytometry. In our randomized study, we found
      the decreased levels of three aforementioned factors compared to levels in
      patients receiving regular blood transfusion (RT). This study showed that BMT in
      beta-thalassemia patients decreases the levels of circulating PS-expressing RBCs,
      their MPs, and procoagulant platelets when compared to patients who received RT.
      Normalized levels of these coagulation markers may provide the supportive
      evidence of the effectiveness of BMT for curing thalassemia.

PMID- 28748285
TI  - Toward the Standardization of Mycological Examination of Sputum Samples in Cystic
      Fibrosis: Results from a French Multicenter Prospective Study.
AB  - Fungal respiratory colonization of cystic fibrosis (CF) patients emerges as a new
      concern; however, the heterogeneity of mycological protocols limits
      investigations. We first aimed at setting up an efficient standardized protocol
      for mycological analysis of CF sputa that was assessed during a prospective,
      multicenter study: "MucoFong" program (PHRC-06/1902). Sputa from 243 CF patients
      from seven centers in France were collected over a 15-month period and submitted
      to a standardized protocol based on 6 semi-selective media. After mucolytic
      pretreatment, sputa were plated in parallel on cycloheximide-enriched (ACT37),
      erythritol-enriched (ERY37), benomyl dichloran-rose bengal (BENO37) and
      chromogenic (CAN37) media incubated at 37  degrees C and on Sabouraud
      chloramphenicol (SAB27) and erythritol-enriched (ERY27) media incubated at 20-27 
      degrees C. Each plate was checked twice a week during 3 weeks. Fungi were
      conventionally identified; time for detection of fungal growth was noted for each
      species. Fungal prevalences and media performances were assessed; an optimal
      combination of media was determined using the Chi-squared automatic interaction
      detector method. At least one fungal species was isolated from 81% of sputa.
      Candida albicans was the most prevalent species (58.8%), followed by Aspergillus
      fumigatus (35.4%). Cultivation on CAN37, SAB27, ACT37 and ERY27 during 16 days
      provided an optimal combination, detecting C. albicans, A. fumigatus,
      Scedosporium apiospermum complex and Exophiala spp. with sensitivities of 96.5,
      98.8, 100 and 100%. Combination of these four culture media is recommended to
      ensure the growth of key fungal pathogens in CF respiratory specimens. The use of
      such consensual protocol is of major interest for merging results from future
      epidemiological studies.

PMID- 28748287
TI  - Presence of acute and chronic renal failure in patients with paroxysmal nocturnal
      hemoglobinuria: results of a retrospective analysis from the Spanish PNH
      Registry.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening blood
      disease. With the advent of eculizumab treatment, renal function has
      substantially improved, although no data from real-world clinical practice are
      available. An observational, retrospective, multicenter study was conducted in
      Spain on clinical data obtained from outpatient visits of patients with PNH
      (Spanish PNH Registry) who had experienced acute (ARF) or chronic (CRF) renal
      failure. Of the 128 patients registered (April 2014), 60 were diagnosed with
      classic PNH. Twenty-seven (45.0%) patients with a mean age of 48.5 (+/-16.2)
      years had renal failure, ARF or CRF, and were included in this study. Near half
      of the patients (n = 13; 48.1%) presented with ARF alone, 33.3% (n = 9) had CRF
      with episodes of ARF, while 18.5% (n = 5) were diagnosed with CRF alone. For
      patients with diagnosis of PNH and renal failure (n = 27), the median time to the
      first ARF episode was 6.5 (CI 95%; 2.2, 14.9) years, whereas the median to the
      diagnosis of CRF was 14.5 (CI 95%; 3.8, 19.2) years after the diagnosis of PNH.
      Patients with ARF (n = 22) were treated with eculizumab and did not experience
      new episodes of ARF, except for one patient with sepsis. Of the patients with
      CRF, two received treatment without experiencing further episodes of ARF. Sixteen
      patients who completed treatment (11 with ARF and 5 with ARF + CRF) recovered
      from the episode of ARF or from CRF. Of the remaining patients treated with
      eculizumab, one patient improved from stages III to II, three patients stabilized
      without showing disease progression, and one patient progressed from stages III
      to IV. Treatment with eculizumab in PNH patients has beneficial effects on renal
      function, preventing ARF and progression to CRF.

PMID- 28748288
TI  - Talaromyces sayulitensis, Acidiella bohemica and Penicillium citrinum in
      Brazilian oil shale by-products.
AB  - Fine shale particles and retorted shale are waste products generated during the
      oil shale retorting process. These by-products are small fragments of mined shale
      rock, are high in silicon and also contain organic matter, micronutrients,
      hydrocarbons and other elements. The aims of this study were to isolate and to
      evaluate fungal diversity present in fine shale particles and retorted shale
      samples collected at the Schist Industrialization Business Unit (Six)-Petrobras
      in Sao Mateus do Sul, State of Parana, Brazil. Combining morphology and internal
      transcribed spacer (ITS) sequence, a total of seven fungal genera were
      identified, including Acidiella, Aspergillus, Cladosporium, Ochroconis,
      Penicillium, Talaromyces and Trichoderma. Acidiella was the most predominant
      genus found in the samples of fine shale particles, which are a highly acidic
      substrate (pH 2.4-3.6), while Talaromyces was the main genus in retorted shale
      (pH 5.20-6.20). Talaromyces sayulitensis was the species most frequently found in
      retorted shale, and Acidiella bohemica in fine shale particles. The presence of
      T. sayulitensis, T. diversus and T. stolli in oil shale is described herein for
      the first time. In conclusion, we have described for the first time a snapshot of
      the diversity of filamentous fungi colonizing solid oil shale by-products from
      the Irati Formation in Brazil.

PMID- 28748289
TI  - Genetic recombinational events in prokaryotes and their viruses: insight into the
      study of evolution and biodiversity.
AB  - The exact meaning of sexual reproduction and the precise evolutionary period at
      which recombination first took place remains the subject of intense debates.
      Despite some unity in biochemical organisation of genetic recombination, a
      plethora of mechanisms are found to exist in microbes and their viruses. Some
      routes used by viruses bypass barriers to genetic heterology and provide bacteria
      with genes conferring a selective advantage, and some contribute to genome
      enlargement. The present review aims at highlighting the diversity of such
      mechanisms with a particular focus on spontaneous zygogenesis (or Z-mating). The
      latter mode of genetic recombination, which was recently discovered in
      Escherichia coli, resembles gamete fusion in eukaryotes in that it involves
      complete genetic mixing. Vertical and horizontal evolution through mutations and
      homo- or heterospecific Z-mating can be monitored to some extent, providing a
      mean to interrogate the mechanisms of evolution in a way similar to introgression
      and symbiogenesis. The question arises as to whether Z-mating might represent a
      remainder of what happened in the very first organisms appearing on earth, as
      well as recombination events among viruses.

PMID- 28748290
TI  - Selection for novel, acid-tolerant Desulfovibrio spp. from a closed Transbaikal
      mine site in a temporal pH-gradient bioreactor.
AB  - Almost all the known isolates of acidophilic or acid-tolerant sulphate-reducing
      bacteria (SRB) belong to the spore-forming genus Desulfosporosinus in the
      Firmicutes. The objective of this study was to isolate acidophilic/acid-tolerant
      members of the genus Desulfovibrio belonging to deltaproteobacterial SRB. The
      sample material originated from microbial mat biomass submerged in mine water and
      was enriched for sulphate reducers by cultivation in anaerobic medium with
      lactate as an electron donor. A stirred tank bioreactor with the same medium
      composition was inoculated with the sulphidogenic enrichment. The bioreactor was
      operated with a temporal pH gradient, changing daily, from an initial pH of 7.3
      to a final pH of 3.7. Among the bacteria in the bioreactor culture, Desulfovibrio
      was the only SRB group retrieved from the bioreactor consortium as observed by
      16S rRNA-targeted denaturing gradient gel electrophoresis. Moderately
      acidophilic/acid-tolerant isolates belonged to Desulfovibrio aerotolerans
      Desulfovibrio carbinophilus-Desulfovibrio magneticus and Desulfovibrio
      idahonensis-Desulfovibrio mexicanus clades within the genus Desulfovibrio. A
      moderately acidophilic strain, Desulfovibrio sp. VK (pH optimum 5.7) and acid
      tolerant Desulfovibrio sp. ED (pH optimum 6.6) dominated in the bioreactor
      consortium at different time points and were isolated in pure culture.

PMID- 28748291
TI  - Predictors of outcomes after arthroscopic transosseous equivalent rotator cuff
      repair in 155 cases: a propensity score weighted analysis of knotted and knotless
      self-reinforcing repair techniques at a minimum of 2 years.
AB  - PURPOSE: To evaluate the outcomes of two commonly used transosseous-equivalent
      (TOE) arthroscopic rotator cuff repair (RCR) techniques for full-thickness
      supraspinatus tendon tears (FTST) using a robust multi-predictor model. METHODS:
      155 shoulders in 151 patients (109 men, 42 women; mean age 59 +/- 10 years) who
      underwent arthroscopic RCR of FTST, using either a knotted suture bridging (KSB)
      or a knotless tape bridging (KTB) TOE technique were included. ASES and SF-12 PCS
      scores assessed at a minimum of 2 years postoperatively were modeled using
      propensity score weighting in a multiple linear regression model. Patients able
      to return to the study center underwent a follow-up MRI for evaluation of rotator
      cuff integrity. RESULTS: The outcome data were available for 137 shoulders (88%;
      n = 35/41 KSB; n = 102/114 KTB). Seven patients (5.1%) that underwent revision
      rotator cuff surgery were considered failures. The median postoperative ASES
      score of the remaining 130 shoulders was 98 at a mean follow-up of 2.9 years
      (range 2.0-5.4 years). A higher preoperative baseline outcome score and a longer
      follow-up had a positive effect, whereas a previous RCR and workers' compensation
      claims (WCC) had a negative effect on final ASES or SF 12 PCS scores. The repair
      technique, age, gender and the number of anchors used for the RCR had no
      significant influence. Fifty-two patients returned for a follow-up MRI at a mean
      of 4.4 years postoperatively. Patients with a KSB RCR were significantly more
      likely to have an MRI-diagnosed full-thickness rotator cuff re-tear (p < 0.05).
      CONCLUSIONS: Excellent outcomes can be achieved at a minimum of 2 years following
      arthroscopic KSB or KTB TOE RCR of FTST. The preoperative baseline outcome score,
      a prior RCR, WCC and the length of follow-up significantly influenced the outcome
      scores. The repair technique did not affect the final functional outcomes, but
      patients with KTB TOE RCR were less likely to have a full-thickness rotator cuff
      re-tear. LEVEL OF EVIDENCE: Level III, Retrospective Comparative Study.

PMID- 28748292
TI  - Systematic CT evaluation of reduction and hardware positioning of surgically
      treated calcaneal fractures: a reliability analysis.
AB  - INTRODUCTION: Up to date, there is a lack of reliable protocols that
      systematically evaluate the quality of reduction and hardware positioning of
      surgically treated calcaneal fractures. Based on international consensus, we
      previously introduced a 23-item scoring protocol evaluating the reduction and
      hardware positioning in these fractures based on postoperative computed
      tomography. The current study is a reliability analysis of the described scoring
      protocol. METHODS: Three raters independently and systematically evaluated
      anonymized postoperative CT scans of 102 surgically treated calcaneal fractures.
      A selection of 25 patients was scored twice by all individual raters to calculate
      intra-rater reliability. The scoring protocol consisted of 23 items addressing
      quality of reduction and hardware positioning. Each of these four-option
      questions was answered as: 'optimal', 'suboptimal (but not needing revision)',
      'not acceptable (needing revision)' or 'not judgeable'. We used intraclass
      correlation coefficients (ICC's) to calculate inter- and intra-rater reliability.
      RESULTS: Inter-rater reliability of the overall 23-item protocol was good (ICC
      0.66, 95% CI 0.64-0.69). Individual items that scored an inter-rater ICC >=0.60
      included evaluation of the calcaneocuboid joint, the posterior talocalcaneal
      joint, the anterior talocalcaneal joint, the position of the plate and
      sustentaculum screws and screws protruding the tuber and medial wall. The intra
      rater reliability for the overall protocol was good for all three individual
      raters with ICC's between 0.60 and 0.70. CONCLUSION: Our scoring protocol for the
      radiological evaluation of operatively treated calcaneal fractures is reliable in
      terms of inter- and intra-rater reliability.

PMID- 28748293
TI  - Racial disparities in outcomes of operatively treated lower extremity fractures.
AB  - PURPOSE: Whether racial differences are associated with function in the long term
      following surgical repair of lower extremity fractures has not been investigated.
      The purpose of this study is to compare how race affects function at 3, 6 and 12
      months post-surgery following certain lower extremity fractures. METHODS: Four
      hundred and eighteen patients treated operatively for a lower extremity fracture
      (199 tibial plateau, 39 tibial shaft, and 180 rotational ankle fractures) were
      prospectively followed for 1 year. Race was stratified into four groups:
      Caucasian, African-American, Hispanic origin, and other. Long-term outcomes were
      evaluated using the short musculoskeletal function assessment (SMFA) and pain
      scores were assessed at 3, 6 months and 1 year. RESULTS: There were 223 (53.3%)
      Caucasians, 72 (17.2%) African-Americans, 53 (12.4%) Hispanics, and 71 (17.0%)
      patients from other ethnic groups, included in our study population. Minority
      patients (African-American, Hispanics, etc.) were more likely to be involved in
      high velocity mechanisms of injury and tended to have a greater percentage of
      open fractures. Although there were no differences in the rate of wound
      complications or reoperations, long-term functional outcomes were worse in
      minority patients as assessed by pain scores at 6 months and functional outcome
      scores at 3, 6 and 12 months. Multivariate analysis revealed that only African
      American and Hispanic race continued to be independent predictors of worse
      functional outcomes at 12 months. CONCLUSIONS: Racial minorities and those on
      medicaid had poorer long-term function following fractures of the lower
      extremity. While minority patients were involved in more high velocity accidents,
      this was not an independent predictor of worse outcomes. These disparities may
      result from multifactorial socioeconomic factors, including socioeconomic status
      and education levels that were not controlled in our study. LEVEL OF EVIDENCE:
      Prognostic Level III.

PMID- 28748295
TI  - ?

PMID- 28748294
TI  - [Clinical Trials with Medicinal Products : Changes imposed by the new Clinical
      Trial Regulation].

PMID- 28748296
TI  - ?

PMID- 28748297
TI  - ?

PMID- 28748298
TI  - Comparison of sodium hypochlorite extrusion by five irrigation systems using an
      artificial root socket model and a quantitative chemical method.
AB  - OBJECTIVES: This is to compare the volumes of irrigant apically extruded by five
      irrigation systems in an artificial socket model simulating clinical conditions.
      MATERIALS AND METHODS: Twenty extracted human single-rooted teeth were enlarged
      to size 40/04 and then embedded in silicone impression material. The root canal
      space was irrigated with nominal 3% sodium hypochlorite (NaOCl) using standard
      needle irrigation (SNI) with a 30-gauge notched needle, EndoActivator (EA), XP
      Endo Finisher (XP Endo), EndoVac (EV), and photon-induced photoacoustic streaming
      (PIPS). Extruded NaOCl was collected, reacted with taurine to form taurine
      monochloramine, and absorbance of taurine-monochloramine was measured at 252 nm
      using a spectrophotometer. The five irrigation systems were compared with
      repeated measures ANOVA and pairwise comparisons. RESULTS: The EV group had very
      low extrusion (mean +/- SD = 0.12 +/- 0.2 MUL) and differed significantly from
      the other four groups (P <= 0.001). Larger volumes of irrigant were extruded in
      the other irrigation groups. There were no significant differences in the
      extruded volumes among the SNI (7.4 +/- 3.4 MUL), EA (7.0 +/- 6.1 MUL), and XP
      Endo (7.8 +/- 4.1 MUL) groups (P = 1). The PIPS group had the highest mean
      extruded volume (12.9 +/- 6.8 MUL) and differed significantly from SNI (P =
      0.030), EV (P < 0.0005), and EA (P = 0.02), but not XP Endo (P = 0.154).
      CONCLUSION: Under the in vitro conditions of this study, irrigant extrusion
      appears unavoidable unless negative pressure irrigation such as EV is used. PIPS
      extrudes more irrigant than other systems, while SNI, EA, and XP Endo extrude
      similar volumes of irrigant. CLINICAL RELEVANCE: The findings help clinicians
      select the optimal irrigation system to avoid irrigant extrusion.

PMID- 28748299
TI  - Acculturation Strategies and Symptoms of Depression: The Mediators of
      Atherosclerosis in South Asians Living in America (MASALA) Study.
AB  - Using latent class analysis, we previously identified three acculturation
      strategies employed by South Asian immigrants in the US. Members of the
      Separation class showed a preference for South Asian culture over US culture,
      while members of the Assimilation class showed a preference for US culture, and
      those in the Integration class showed a similar preference for South Asian and US
      cultures. The purpose of this study was to examine associations between these
      acculturation strategies and symptoms of depression, a common yet underdiagnosed
      and undertreated mental disorder. We used data from the Mediators of
      Atherosclerosis in South Asians Living in America (MASALA) study (n = 856). Data
      were collected between October 2010 and March 2013 in the San Francisco Bay Area
      and Chicago. Depressive symptoms were assessed using the CES-D Scale. Applying a
      simple new method to account for uncertainty in class assignment when modeling
      latent classes as an exposure, we found that respondents in the Separation class
      had more depressive symptoms than those in the Integration class, but only after
      taking into account self-reported social support (b = 0.11; p = 0.05). There were
      no differences in depressive symptoms among those in the Assimilation class vs.
      those in the Integration class (b = -0.06; p = 0.41). Social support may protect
      against elevated symptoms of depression in South Asian immigrants with lower
      levels of integration into US culture.

PMID- 28748300
TI  - Psychological Distress of Ethnically Diverse Adult Caregivers in the California
      Health Interview Survey.
AB  - This study examined factors associated with psychological distress for culturally
      diverse family caregivers using a population-based sample. Data were analyzed
      from the 6634 caregivers of adults (i.e. elderly as well as non-elderly) who self
      reported as non-Hispanic White, Mexican, Chinese, or Vietnamese in the 2009
      California Health Interview Survey. Simple and multiple regression analyses were
      conducted to assess the potential influence of race/ethnicity, caregiving
      context, and social contextual variables on psychological distress. Analyses that
      included moderators showed that while more education was associated with less
      distress for White caregivers, it was associated with more distress for
      Vietnamese and Chinese caregivers. Identifying the caregiving and contextual
      variables associated with psychological distress is critical for tailoring
      interventions towards those who need the most help-in this case, possibly less
      educated White caregivers and more educated Asian American caregivers.

PMID- 28748301
TI  - The aflatoxin-detoxifizyme specific expression in the parotid gland of transgenic
      pigs.
AB  - Producing aflatoxin-detoxifizyme (ADTZ) in pigs to control the AFT contamination
      of pig feed is a new research strategy by transgenic technology. In this study,
      transgenic pigs specifically expressing ADTZ gene in the parotid gland were
      successfully produced by somatic cell nuclear transfer technology. The ADTZ
      activity in saliva of 6 transgenic pigs was found to be 7.11 +/- 2.63 U/mL. The
      feeding trial with aflatoxin (AFT) results showed that there were significant
      difference about the serum biochemical index such as total protein (TP), albumin
      (ALB), globulin (GLB) contents and alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) activity and AFT residues in serum and liver between the
      pigs in the test treatment (transgenic pigs) producing ADTZ and those in the
      positive control (P < 0.05). In order to investigate the inheritance of the
      transgene, 11 G1 transgenic pigs were successfully obtained. The ADTZ activity in
      saliva of 11 G1 transgenic pigs was found to be 5.82 +/- 1.53 U/mL. The feeding
      trial with AFT results showed that the serum biochemical index containing TP, ALB
      and GLB contents and ALT and AST activity and AFB1 residues in serum and liver of
      the pigs in the test treatment (transgenic pigs) producing ADTZ were
      significantly different than those in the positive control (P < 0.05). The above
      results demonstrated that ADTZ produced in transgenic pigs could improve the
      effect of the AFT contamination of feed on pigs.

PMID- 28748302
TI  - Effect of combination of fractional CO2 laser and narrow-band ultraviolet B
      versus narrow-band ultraviolet B in the treatment of non-segmental vitiligo.
AB  - The present study was designed to evaluate the effect of combining fractional CO2
      laser with narrow-band ultraviolet B (NB-UVB) versus NB-UVB in the treatment of
      non-segmental vitiligo. The study included 20 patients with non-segmental stable
      vitiligo. They were divided into two groups. Group I received a single session of
      fractional CO2 laser therapy on the right side of the body followed by NB-UVB
      phototherapy twice per week for 8 weeks. Group II received a second session of
      fractional CO2 laser therapy after 4 weeks from starting treatment with NB-UVB.
      The vitiligo lesions were assessed before treatment and after 8 weeks of
      treatment by VASI. At the end of the study period, the vitiligo area score index
      (VASI) in group I decreased insignificantly on both the right (-2.6%) and left (
      16.4%) sides. In group II, VASI increased insignificantly on the right (+14.4%)
      and left (+2.5%) sides. Using Adobe Photoshop CS6 extended program to measure the
      area of vitiligo lesions, group I showed a decrease of -1.02 and -6.12% in the
      mean area percentage change of vitiligo lesions on the right and left sides,
      respectively. In group II the change was +9.84 and +9.13% on the right and left
      sides, respectively. In conclusion, combining fractional CO2 laser with NB-UVB
      for the treatment of non-segmental vitiligo did not show any significant
      advantage over treatment with NB-UVB alone. Further study of this combination for
      longer durations in the treatment of vitiligo is recommended.

PMID- 28748303
TI  - A mean field model for movement induced changes in the beta rhythm.
AB  - In electrophysiological recordings of the brain, the transition from high
      amplitude to low amplitude signals are most likely caused by a change in the
      synchrony of underlying neuronal population firing patterns. Classic examples of
      such modulations are the strong stimulus-related oscillatory phenomena known as
      the movement related beta decrease (MRBD) and post-movement beta rebound (PMBR).
      A sharp decrease in neural oscillatory power is observed during movement (MRBD)
      followed by an increase above baseline on movement cessation (PMBR). MRBD and
      PMBR represent important neuroscientific phenomena which have been shown to have
      clinical relevance. Here, we present a parsimonious model for the dynamics of
      synchrony within a synaptically coupled spiking network that is able to replicate
      a human MEG power spectrogram showing the evolution from MRBD to PMBR.
      Importantly, the high-dimensional spiking model has an exact mean field
      description in terms of four ordinary differential equations that allows
      considerable insight to be obtained into the cause of the experimentally observed
      time-lag from movement termination to the onset of PMBR (~ 0.5 s), as well as the
      subsequent long duration of PMBR (~ 1 - 10 s). Our model represents the first to
      predict these commonly observed and robust phenomena and represents a key step in
      their understanding, in health and disease.

PMID- 28748304
TI  - The eye fluke Tylodelphys clavata affects prey detection and intraspecific
      competition of European perch (Perca fluviatilis).
AB  - Parasites that occupy the eyes of fish have the potential to affect visual
      perception and consequently alter the host's behaviour, as these organs provide
      information about their surroundings. In an experimental study, the feeding
      behaviour of European perch (Perca fluviatilis) infested with the eye fluke
      Tylodelphys clavata was examined. The results showed that an individual's ability
      to identify and approach food items was negatively affected by the infestation
      intensity of T. clavata. Additionally, the foraging success of an individual was
      reduced in competition with another, less heavily infested conspecific, when the
      same food resource was exploited. These alterations in the ability to locate food
      may have important consequences on the feeding strategy of the fish. Furthermore,
      the impaired feeding capability caused by T. clavata may also increase the
      predation risk as heavily infested fish need to spend more time foraging to
      attain a rate of food intake equivalent to less infested conspecifics.

PMID- 28748305
TI  - [Imaging in rheumatology].

PMID- 28748306
TI  - Low emotion-oriented coping and informal help-seeking behaviour as major
      predictive factors for improvement in major depression at 5-year follow-up in the
      adult community.
AB  - PURPOSE: Given the broad range of biopsychosocial difficulties resulting from
      major depressive disorder (MDD), reliable evidence for predictors of improved
      mental health is essential, particularly from unbiased prospective community
      samples. Consequently, a broad spectrum of potential clinical and non-clinical
      predictors of improved mental health, defined as an absence of current major
      depressive episode (MDE) at follow-up, were examined over a 5-year period in an
      adult community sample. METHODS: The longitudinal population-based PsyCoLaus
      study from the city of Lausanne, Switzerland, was used. Subjects having a
      lifetime MDD with a current MDE at baseline assessment were selected, resulting
      in a subsample of 210 subjects. Logistic regressions were applied to the data.
      RESULTS: Coping styles were the most important predictive factors in the present
      study. More specifically, low emotion-oriented coping and informal help-seeking
      behaviour at baseline were associated with the absence of an MDD diagnosis at
      follow-up. Surprisingly, neither formal help-seeking behaviour, nor
      psychopharmacological treatment, nor childhood adversities, nor depression
      subtypes turned out to be relevant predictors in the current study. CONCLUSIONS:
      The paramount role of coping styles as predictors of improvement in depression
      found in the present study might be a valuable target for resource-oriented
      therapeutic models. On the one hand, the positive impact of low emotion-oriented
      coping highlights the utility of clinical interventions interrupting excessive
      mental ruminations during MDE. On the other hand, the importance of informal
      social networks raises questions regarding how to enlarge the personal network of
      affected subjects and on how to best support informal caregivers.

PMID- 28748308
TI  - Smoking, health-related quality of life and economic evaluation.
AB  - BACKGROUND AND AIMS: The economic evaluation of tobacco control policies requires
      the adoption of assumptions about the impact of changes in smoking status on
      health-related quality of life (HRQoL). Estimates for such impacts are necessary
      for different populations. This paper aims to test whether smoking status has an
      independent effect on HRQoL over and above the effect derived from the increased
      likelihood of suffering a tobacco related disease, and to calculate utility
      values for the Spanish population. METHODS: Using data from the Spanish Encuesta
      Nacional de Salud of 2011-12, we estimate statistical models for HRQoL as
      measured by the EQ-5D-5L instrument as a function of smoking status. We include a
      comprehensive set of controls for biological, clinical, lifestyle and
      socioeconomic characteristics. RESULTS: Smoking status has an independent,
      statistically significant effect on HRQoL. However, the size of the effect is
      small. The typical smoking related diseases, such as lung cancer, are associated
      with a reduction in HRQoL about 5 times larger than the difference between
      current smokers and never smokers. CONCLUSION: Attributing substantive HRQoL
      gains to quitting smoking as well as accounting for the concomitant HRQoL gain
      derived from a smaller likelihood of contracting tobacco related diseases might
      lead to an overestimation of the benefits of tobacco control policies.
      Nonetheless, the relatively large drops in HRQoL associated with being diagnosed
      with diseases that might be causally linked to tobacco suggest that such diseases
      should not be omitted from the economic evaluations of tobacco control policies.

PMID- 28748307
TI  - Systematic review of mental health disorders and intimate partner violence
      victimisation among military populations.
AB  - PURPOSE: There is growing awareness of the problem of intimate partner violence
      (IPV) among military populations. IPV victimisation has been shown to be
      associated with mental disorder. A better understanding of the link between IPV
      and mental disorder is needed to inform service development to meet the needs of
      military families. We aimed to systematically review the literature on the
      association between IPV victimisation and mental health disorders among military
      personnel. METHODS: Searches of four electronic databases (Embase, Medline,
      PsycINFO, and Web of Science) were supplemented by reference list screening.
      Heterogeneity among studies precluded a meta-analysis. RESULTS: Thirteen studies
      were included. There was stronger evidence for an association between IPV and
      depression/alcohol problems than between IPV and PTSD. An association between IPV
      and mental health problems was more frequently found among veterans compared to
      active duty personnel. However, the link between IPV and alcohol misuse was more
      consistently found among active duty samples. Finally, among active duty
      personnel psychological IPV was more consistently associated with
      depression/alcohol problems than physical/sexual IPV. The review highlighted the
      lack of research on male IPV victimisation in the military. CONCLUSIONS: There is
      evidence that the burden of mental health need may be significant among military
      personnel who are victims of IPV. The influence of attitudes towards gender in
      the military on research in this area is discussed. Further research is needed to
      inform development of services and policy to reduce IPV victimisation and the
      mental health consequences among military personnel.

PMID- 28748309
TI  - Interaction of Zn(II)bleomycin-A2 and Zn(II)peplomycin with a DNA hairpin
      containing the 5'-GT-3' binding site in comparison with the 5'-GC-3' binding site
      studied by NMR spectroscopy.
AB  - Bleomycins are a group of glycopeptide antibiotics synthesized by Streptomyces
      verticillus that are widely used for the treatment of various neoplastic
      diseases. These antibiotics have the ability to chelate a metal center, mainly
      Fe(II), and cause site-specific DNA cleavage. Bleomycins are differentiated by
      their C-terminal regions. Although this antibiotic family is a successful course
      of treatment for some types of cancers, it is known to cause pulmonary fibrosis.
      Previous studies have identified that bleomycin-related pulmonary toxicity is
      linked to the C-terminal region of these drugs. This region has been shown to
      closely interact with DNA. We examined the binding of Zn(II)peplomycin and
      Zn(II)bleomycin-A2 to a DNA hairpin of sequence 5'-CCAGTATTTTTACTGG-3',
      containing the binding site 5'-GT-3', and compared the results with those
      obtained from our studies of the same MBLMs bound to a DNA hairpin containing the
      binding site 5'-GC-3'. We provide evidence that the DNA base sequence has a
      strong impact in the final structure of the drug-target complex.

PMID- 28748310
TI  - Long-Term Outcome of Adenosine Deaminase-Deficient Patients-a Single-Center
      Experience.
AB  - PURPOSE: Inherited defects in the adenosine deaminase (ADA) enzyme can cause
      severe combined immune deficiency (SCID) and systemic abnormalities. Management
      options for ADA-deficient patients include enzyme replacement therapy (ERT),
      hematopoietic stem cell transplantation (HSCT), and gene therapy (GT). Here, we
      describe the long-term benefits of these treatments. METHODS: Survival,
      infections, systemic sequelae, and laboratory assessments were recorded for all
      ADA-deficient SCID patients, managed at a single center since 1985, who survived
      5 or more years following treatment. RESULTS: Of 20 ADA-deficient patients, the 8
      (40%) who survived 5 or more years (range 6-29.5 years, median 14 years) were
      included in the study. Among the long-term survivors, two patients were treated
      exclusively with ERT, five underwent HSCT (three from HLA-matched sibling donors,
      two from HLA-mismatched related donors), and one received GT. The long-term
      survivors often suffered from recurrent respiratory infections; however,
      opportunistic infections occurred in only one patient. Systemic sequelae included
      lung disease such as bronchiectasis and asthma (four patients), neurologic
      abnormalities (six patients), metabolic disturbances (two patients), allergy and
      autoimmunity (six patients), and neoplasms (three patients). Normal CD4+ T cell
      numbers and function, as well as antibody production, were usually observed after
      HSCT and GT, but not after ERT. Late deaths occurred in two patients at 15 and 25
      years after HSCT, respectively, and were attributed to respiratory failure.
      CONCLUSIONS: ADA-deficient patients commonly suffer from long-term complications,
      emphasizing the need for improved management and for multi-disciplinary follow
      up.

PMID- 28748311
TI  - Advantages of melodic over rhythmic movement sonification in bimanual motor skill
      learning.
AB  - An important question for skill acquisition is whether and how augmented feedback
      can be designed to improve the learning of complex skills. Auditory information
      triggered by learners' actions, movement sonification, can enhance learning of a
      complex bimanual coordination skill, specifically polyrhythmic bimanual shape
      tracing. However, it is not clear whether the coordination of polyrhythmic
      sequenced movements is enhanced by auditory-specified timing information alone or
      whether more complex sound mappings, such as melodic sonification, are necessary.
      Furthermore, while short-term retention of bimanual coordination performance has
      been shown with movement sonification training, longer term retention has yet to
      be demonstrated. In the present experiment, participants learned to trace a
      diamond shape with one hand while simultaneously tracing a triangle with the
      other to produce a sequenced 4:3 polyrhythmic timing pattern. Two groups of
      participants received real-time auditory feedback during training: melodic
      sonification (individual movements triggered a separate note of a melody) and
      rhythmic sonification (each movement triggered a percussive sound), while a third
      control group received no augmented feedback. Task acquisition and performance in
      immediate retention were superior in the melodic sonification group as compared
      to the rhythmic sonification and control group. In a 24-h retention phase, a
      decline in performance in the melodic sonification group was reversed by brief
      playback of the target pattern melody. These results show that melodic
      sonification of movement can provide advantages over augmented feedback which
      only provides timing information by better structuring the sequencing of timed
      actions, and also allow recovery of complex target patterns of movement after
      training. These findings have important implications for understanding the role
      of augmented perceptual information in skill learning, as well as its application
      to real-world training or rehabilitation scenarios.

PMID- 28748312
TI  - The extended object-grasping network.
AB  - Grasping is the most important skilled motor act of primates. It is based on a
      series of sensorimotor transformations through which the affordances of the
      objects to be grasped are transformed into appropriate hand movements. It is
      generally accepted that a circuit formed by inferior parietal areas AIP and PFG
      and ventral premotor area F5 represents the core circuit for sensorimotor
      transformations for grasping. However, selection and control of appropriate grip
      should also depend on higher-order information, such as the meaning of the object
      to be grasped, and the overarching goal of the action in which grasping is
      embedded. In this review, we describe recent findings showing that specific
      sectors of the ventrolateral prefrontal cortex are instrumental in controlling
      higher-order aspects of grasping. We show that these prefrontal sectors control
      the premotor cortex through two main gateways: the anterior subdivision of
      ventral area F5-sub-area F5a-, and the pre-supplementary area (area F6). We then
      review functional studies showing that both F5a and F6, besides being relay
      stations of prefrontal information, also play specific roles in grasping. Namely,
      sub-area F5a is involved in stereoscopic analysis of 3D objects, and in planning
      cue-dependent grasping activity. As for area F6, this area appears to play a
      crucial role in determining when to execute the motor program encoded in the
      parieto-premotor circuit. The recent discovery that area F6 contains a set of
      neurons encoding specific grip types suggests that this area, besides controlling
      "when to go", also may control the grip type, i.e., "how to go". We conclude by
      discussing clinical syndromes affecting grasping actions and their possible
      mechanisms.

PMID- 28748313
TI  - New approach in evaluation of ceramic-polymer composite bioactivity and
      biocompatibility.
AB  - Regeneration of bone defects was promoted by a novel beta-glucan/carbonate
      hydroxyapatite composite and characterized by Raman spectroscopy, microCT and
      electron microscopy. The elastic biomaterial with an apatite-forming ability was
      developed for bone tissue engineering and implanted into the critical-size
      defects of rabbits' tibiae. The bone repair process was analyzed on non
      decalcified bone/implant sections during a 6-month regeneration period. Using
      spectroscopic methods, we were able to determine the presence of amides, lipids
      and assign the areas of newly formed bone tissue. Raman spectroscopy was also
      used to assess the chemical changes in the composite before and after the
      implantation process. SEM analyses showed the mineralization degree in the defect
      area and that the gap size decreased significantly. Microscopic images revealed
      that the implant debris were interconnected to the poorly mineralized inner side
      of a new bone tissue. Our study demonstrated that the composite may serve as a
      biocompatible background for collagen ingrowth and exhibits the advantages of
      applying Raman spectroscopy, SEM and microCT in studying these samples.

PMID- 28748314
TI  - The Present Status of Fecal Microbiota Transplantation and Its Value in the
      Elderly.
AB  - OPINION STATEMENT: PURPOSE OF REVIEW: This article will review current literature
      describing fecal microbiota transplantation (FMT) in the treatment of various
      diseases, and its potential role in elderly patients (age >= 65 years). RECENT
      FINDINGS: Research on FMT has blossomed in the last decade and its pivotal role
      in the treatment of recurrent Clostridium difficile infection (CDI) has been
      recognized by the American College of Gastroenterology in the latest guidelines.
      There is also emerging evidence that FMT may be beneficial in the treatment of
      severe and/or complicated CDI refractory to medical therapy, resulting in
      decreased rates of colectomy and mortality. In the elderly, CDI is associated
      with markedly higher rates of mortality and colectomy; outcomes are even worse
      when patients have underlying inflammatory bowel disease (IBD). While the
      majority of patients who receive FMT for CDI are older, only a handful of studies
      focused specifically on FMT treatment outcomes and safety in this age group.
      Current data corroborate the efficacy and safety profile of FMT, while also
      supporting its use for recurrent, severe, and/or complicated CDI in the elderly
      population. FMT is recommended for the treatment of recurrent, severe, and/or
      complicated CDI in patients older than 65 years of age. It may be prudent to
      offer FMT earlier in the disease course, possibly after just the second
      recurrence and for the first episode of severe CDI to avert complications
      including colectomy and end-organ failure that elderly patients are more prone to
      developing.

PMID- 28748315
TI  - Interferon-alpha Treatment for Disease Control in Metastatic
      Pheochromocytoma/Paraganglioma Patients.
AB  - Interferon-alpha (IFN-alpha) is recommended in neuroendocrine tumors (NET).
      Malignant pheochromocytoma and paragangliomas (MPPGLs) constitute a rare subgroup
      of NET with few treatment options. IFN-alpha efficacy in patients with MPPGLs was
      evaluated in a single-center retrospective study. Progression-free survival (PFS)
      was the primary endpoint according to RECIST 1.1 and/or PERCIST 1.0, and response
      rate, safety, and symptomatic efficacy were secondary endpoints. Fourteen
      patients received peginterferon alfa-2a (90 to 180 MUg/week) or interferon alfa
      2b (1.5 to 3 million units * 3/week) at our institution between December 2005 and
      February 2014 as the first (n = 7), second (n = 3), or subsequent line (n = 4) of
      treatment. Most of the patients had a slowly progressive disease before IFN-alpha
      initiation. Eight patients were men (57%); the median age was 44. At the
      beginning of treatment, 12 patients had progressive disease demonstrated by FDG
      PET (n = 9), MIBG (n = 1), or CT scan (n = 2). Most of the patients treated (64%)
      had metastatic disease limited to or predominantly located in the bones. During
      IFN-alpha therapy, bone-directed loco-regional treatments were performed in 9
      patients (range 1-4). Median PFS was 17.2 months (95% CI [12.1-58.3]). We
      observed 3 partial metabolic responses, 9 stable diseases, and 2 progressive
      diseases. No partial response according to RECIST 1.1 was observed. Symptomatic
      relief of pain, headaches, diarrhea, or sweating occurred in 6 out of 10
      symptomatic pts. Most frequent all grade IFN-alpha-related toxicities were
      asthenia (n = 10), lymphopenia (n = 7), thrombopenia (n = 6), and anemia (n = 5).
      Median overall survival was 7.5 years (95% CI [4-NR]). This study suggests
      symptomatic response and tumor control effect with interferon-alpha in
      progressive MPPGLs.

PMID- 28748316
TI  - Sleep and Mental Health in the General Population of Elderly Women.
AB  - Sleep and mental health complaints are prevalent in the elderly and share common
      risk factors. We assessed the relationship between sleep and mental health in
      three representative samples of elderly women while controlling for multiple risk
      factors common to both. We performed this cross sectional secondary data analysis
      in 2015 using 2013 data from the Behavioral Risk Factor Surveillance System
      (BRFSS) for females ages 65 years and older from California (N = 1912), Florida
      (N = 9120), and Pennsylvania (N = 2429). We conducted multiple logistic
      regression analysis to assess the relationship between sleep duration group
      (short, moderate/reference, or long) and mental health issues in the past 30 days
      (yes or no) in elderly females, while controlling for multiple covariates. About
      25% of the elderly females reported mental health issues and 20% reported short
      or long sleep durations. In adjusted analysis, compared to the elderly females in
      the moderate sleep duration group (averaging 6-8 h of sleep per day), those in
      the short and long sleep duration groups had increased prevalence of mental
      health issues by 66% and 26%, respectively. Mental health was also related to
      physical health issues including general health status, activity limitations, and
      chronic health conditions. Overall, sleep was related to mental health in
      representative samples of elderly females even after controlling for risk factors
      common to both. Even though we could not determine the direction of influence,
      the findings indicate a need for clinicians to screen their elderly female
      patients for both sleep and mental health issues, especially in those with
      physical health comorbidities.

PMID- 28748318
TI  - Surgical outcome of wide wedge resection in poor-risk patients with clinical-N0
      non-small cell lung cancer.
AB  - OBJECTIVE: Sublobar resection is practically indicated in poor-risk patients
      compromised cardiopulmonary reserve or for small ground-glass opacity-dominant
      adenocarcinomas. The aim of this study was to clarify the surgical outcomes of
      wide wedge resection in poor-risk patients with clinical-N0 non-small cell lung
      cancers. METHODS: Sixty-two poor-risk patients, who underwent wedge resection for
      clinical-N0 lung cancer, were retrospectively reviewed. We defined the ratio of
      the maximum diameter of the consolidation to the maximum tumour diameter as the
      consolidation-to-tumour ratio using high-resolution computed tomography. RESULTS:
      The 5-year overall, recurrence-free, and lung cancer specific survivals of all
      patients were 56.4, 46.6, and 81.1%, respectively, while other malignancies were
      frequently found as causes of death. Overall and recurrence-free survivals were
      favourable in patients with tumour size <=3 cm, consolidation-to-tumour ratio
      <=0.50, solid tumour size <=1.2 cm, carcinoembryonic antigen level <5.0 ng/mL and
      adenocarcinoma. Multivariate Cox proportional hazard model revealed that solid
      tumour size <=1.2 cm and consolidation-to-tumour ratio <=0.50 were independent
      prognostic factors. CT-guided lipiodol marking was applied in 20 patients to
      identify the tumour location had no recurrence. CONCLUSIONS: Wide wedge resection
      could be radical treatment option in poor-risk patients with clinical-N0 non
      small cell lung cancer, though careful follow-up might be necessary for other
      malignancies. Patients with solid tumour <=1.2 cm or ground-glass-dominant lesion
      are good candidates for wedge resection. CT-guided lipiodol marking is a useful
      option to identify the location and safe surgical tumour margin in wedge
      resection.

PMID- 28748320
TI  - The Relationship Between Lesion Localization and Dysphagia in Acute Stroke.
AB  - Factors that can facilitate early identification of individuals at risk of
      dysphagia such as stroke location are potentially of great benefit. The aim of
      this study was to examine the role of hemisphere and lesion location in assessing
      dysphagia pattern and airway invasion as identified through the use of validated,
      standardized interpretation measures for the videofluoroscopic swallowing study.
      Consecutive patients (N = 80) presenting with stroke symptoms who had a first
      time acute ischemic stroke confirmed on diffusion-weighted magnetic resonance
      imaging (DW-MRI) scan participated. Three swallowing outcome variables were
      assessed using regression models: modified barium swallow impairment profile
      (MBSImP) oral impairment (OI) and pharyngeal impairment (PI) scores and
      penetration aspiration scale (PAS) score. Subjects were primarily male and
      demonstrated mild stroke and mild to moderate dysphagia. There was a
      significantly higher likelihood of abnormal PAS scores for infratentorial lesions
      compared to right hemisphere location (Odds ratio: 3.1, SE: 1.8, p = 0.046) and
      for Whites compared to African Americans (Odds ratio: 5.5, SE: 2.6, p = <0.001).
      However, OI scores were higher (worse) in African Americans compared to Whites
      (Beta = -1.2; SE: 0.56; p = 0.037). PI scores had no significant association with
      race or lesion location. Using DW-MRI to identify infratentorial stroke can help
      identify individuals at risk of airway invasion; however, imaging information
      concerning supratentorial infarct hemisphere and location may not be useful to
      predict which individuals with mild stroke are at risk for dysphagia and
      aspiration when admitted with acute stroke symptoms. Future studies should
      explore the role of race in the development of stroke-related dysphagia.

PMID- 28748319
TI  - Diverse action of repeated corticosterone treatment on synaptic transmission,
      neuronal plasticity, and morphology in superficial and deep layers of the rat
      motor cortex.
AB  - One of the adverse effects of prolonged stress in rats is impaired performance of
      skilled reaching and walking tasks. The mechanisms that lead to these
      abnormalities are incompletely understood. Therefore, we compared the effects of
      twice daily repeated corticosterone injections for 7 days on miniature excitatory
      postsynaptic currents (mEPSCs), as well as on synaptic plasticity and morphology
      of layers II/III and V pyramidal neurons of the primary motor cortex (M1) of male
      Wistar rats. Corticosterone treatment resulted in increased frequency, but not
      amplitude, of mEPSCs in layer II/III neurons accompanied by increased complexity
      of the apical part of their dendritic tree, with no changes in the density of
      dendritic spines. The frequency and amplitude of mEPSCs as well as the parameters
      characterizing the complexity of the dendritic tree were not changed in layer V
      cells; however, their dendritic spine density was increased. While corticosterone
      treatment resulted in an increase in the amplitude of field potentials evoked in
      intralaminar connections within layer II/III, it did not influence field
      responses in layer V intralaminar connections, as well as the extent of
      chemically induced layer V long-term potentiation (chemLTP) by the application of
      tetraethylammonium (TEA, 25 mM). However, chemLTP induction in layer II/III was
      impaired in slices prepared from corticosterone-treated animals. These data
      indicate that repeated 7-day administration of exogenous corticosterone induces
      structural and functional plasticity in the M1, which occurs mainly in layer
      II/III pyramidal neurons. These findings shed light on potential sites of action
      and mechanisms underlying stress-induced impairment of motor functions.

PMID- 28748321
TI  - Aqueous ammonia pretreatment of sugar beet pulp for enhanced enzymatic
      hydrolysis.
AB  - Aqueous ammonia pretreatment under various temperatures was applied to enhance
      enzymatic hydrolysis of sugar beet pulp (SBP), and the mechanism of pretreatment
      was evaluated in terms of the enzymatic hydrolysis, chemical composition, pore
      size distribution, crystallinity index, and microstructure. The results showed
      that aqueous ammonia played a vital role in degrading of neutral detergent
      soluble fraction as well as softening and partly exposing of cellulose under
      moderate temperatures. Apertures of various sizes in the SBP tissues were formed,
      specific surface area was increased, and the fiber became rougher after
      pretreatment. The highest reducing sugar yield reached 448.52 mg/g when the SBP
      was pretreated by aqueous ammonia at 80  degrees C for 6 h, which was 2.42 times
      higher than that of the raw SBP. The aqueous ammonia pretreatment improved the
      enzymatic digestibility of SBP, which was a promising method that might be
      explored in ethanol production from SBP.

PMID- 28748322
TI  - Schisandrin B Ameliorates Myocardial Ischemia/Reperfusion Injury Through
      Attenuation of Endoplasmic Reticulum Stress-Induced Apoptosis.
AB  - Schisandrin B (Sch B), an active composition isolated from the fruit of
      Schisandra chinensis, has been proved to possess antiinflammatory, antioxidant
      and anti-endoplasmic reticulum (ER) stress effects in many rodent tissues.
      However, the exact mechanism of cardioprotective effect of Sch B still needs more
      study. Here, we detected the effects of Sch B on myocardial ischemia/reperfusion
      (I/R) injury rats. I/R injury model in this study was established by left
      anterior descending coronary artery ligation for 40 min followed by 1 h of
      reperfusion. Male healthy rats were randomly divided into five groups: the sham,
      I/R, Sch B (20 mg/kg) + I/R, and Sch B (40 mg/kg) + I/R, Sch B (80 mg/kg) + I/R,
      with 10 rats in each group. We showed that Sch B treatment significantly
      protected against myocardial I/R injury, as demonstrated by the decrease in the
      percentage of infarct formation assessed by 2,3,5-triphenyl tetrazolium chloride
      (TTC) staining in representative heart tissue slices, comparing with the I/R
      control group. The levels of creatine kinase (CK), lactate dehydrogenase (LDH),
      malondialdehyde (MDA), and total superoxide dismutase (T-SOD) were tested. The ER
      stress-related proteins such as C/EBP homologous protein (CHOP), activating
      transcription factor 6 (ATF6), and (PKR)-like ER kinase (PERK) were further
      measured by western blot, and their messenger RNA levels were measured by real
      time PCR. The apoptosis of heart tissue cells was also tested through the
      expressions of caspase-9, caspase-3, Bcl-2, and Bax proteins. Collectively, these
      results revealed that Sch B exerts protection role on myocardial I/R injury
      through decreasing oxidative reaction, suppressing ATF6 and PERK pathway, and
      attenuating ER stress-induced apoptosis.

PMID- 28748324
TI  - Alcohol drinking patterns and risk of diabetes: a cohort study of 70,551 men and
      women from the general Danish population.
AB  - AIMS/HYPOTHESIS: Alcohol consumption is inversely associated with diabetes, but
      little is known about the role of drinking patterns. We examined the association
      between alcohol drinking patterns and diabetes risk in men and women from the
      general Danish population. METHODS: This cohort study was based on data from the
      Danish Health Examination Survey 2007-2008. Of the 76,484 survey participants,
      28,704 men and 41,847 women were eligible for this study. Participants were
      followed for a median of 4.9 years. Self-reported questionnaires were used to
      obtain information on alcohol drinking patterns, i.e. frequency of alcohol
      drinking, frequency of binge drinking, and consumption of wine, beer and spirits,
      from which we calculated beverage-specific and overall average weekly alcohol
      intake. Information on incident cases of diabetes was obtained from the Danish
      National Diabetes Register. Cox proportional hazards model was applied to
      estimate HRs and 95% CIs. RESULTS: During follow-up, 859 men and 887 women
      developed diabetes. The lowest risk of diabetes was observed at 14 drinks/week in
      men (HR 0.57 [95% CI 0.47, 0.70]) and at 9 drinks/week in women (HR 0.42 [95% CI
      0.35, 0.51]), relative to no alcohol intake. Compared with current alcohol
      consumers consuming <1 day/week, consumption of alcohol on 3-4 days weekly was
      associated with significantly lower risk for diabetes in men (HR 0.73 [95% CI
      0.59, 0.94]) and women (HR 0.68 [95% CI 0.53, 0.88]) after adjusting for
      confounders and average weekly alcohol amount. CONCLUSIONS/INTERPRETATION: Our
      findings suggest that alcohol drinking frequency is associated with risk of
      diabetes and that consumption of alcohol over 3-4 days per week is associated
      with the lowest risk of diabetes, even after taking average weekly alcohol
      consumption into account.

PMID- 28748323
TI  - Mechanisms of protein homeostasis (proteostasis) maintain stem cell identity in
      mammalian pluripotent stem cells.
AB  - Protein homeostasis, or proteostasis, is essential for cell function,
      development, and organismal viability. The composition of the proteome is
      adjusted to the specific requirements of a particular cell type and status.
      Moreover, multiple metabolic and environmental conditions challenge the integrity
      of the proteome. To maintain the quality of the proteome, the proteostasis
      network monitors proteins from their synthesis through their degradation. Whereas
      somatic stem cells lose their ability to maintain proteostasis with age, immortal
      pluripotent stem cells exhibit a stringent proteostasis network associated with
      their biological function and intrinsic characteristics. Moreover, growing
      evidence indicates that enhanced proteostasis mechanisms play a central role in
      immortality and cell fate decisions of pluripotent stem cells. Here, we will
      review new insights into the melding fields of proteostasis and pluripotency and
      their implications for the understanding of organismal development and survival.

PMID- 28748325
TI  - The Sense of Quality of Life and Religious Strategies of Coping with Stress in
      Prison Inmates.
AB  - The aim of the presented research was to analyze differences in religious
      strategies of coping with stress in a group of prison inmates characterized by
      different levels of the sense of quality of life-general, psychophysical,
      psychosocial, personal, and metaphysical. The participants were 390 males, aged
      19-68 years, serving sentences in prisons in Poland. The measures used were the
      Sense of Quality of Life Questionnaire by M. Stras-Romanowska and K. I.
      Pargament's RCOPE Questionnaire. As expected, individuals with a high sense of
      quality of life-both general and pertaining to specific dimensions-more often
      chose positive religious strategies, whereas participants with a low sense of
      quality of life more often chose negative strategies. The exception was the
      metaphysical aspect of the quality of life: individuals with a high intensity of
      this dimension more often chose some of the positive as well as negative
      religious strategies.

PMID- 28748326
TI  - The Factor Structure of the Spiritual Well-Being Scale in Veterans Experienced
      Chemical Weapon Exposure.
AB  - This study aimed to determine the factor structure of the spiritual well-being
      among a sample of the Iranian veterans. In this methodological research, 211 male
      veterans of Iran-Iraq warfare completed the Paloutzian and Ellison spiritual well
      being scale. Maximum likelihood (ML) with oblique rotation was used to assess
      domain structure of the spiritual well-being. The construct validity of the scale
      was assessed using confirmatory factor analysis (CFA), convergent validity, and
      discriminant validity. Reliability was evaluated with Cronbach's alpha, Theta
      (theta), and McDonald Omega (Omega) coefficients, intra-class correlation
      coefficient (ICC), and construct reliability (CR). Results of ML and CFA
      suggested three factors which were labeled "relationship with God," "belief in
      fate and destiny," and "life optimism." The ICC, coefficients of the internal
      consistency, and CR were >.7 for the factors of the scale. Convergent validity
      and discriminant validity did not fulfill the requirements. The Persian version
      of spiritual well-being scale demonstrated suitable validity and reliability
      among the veterans of Iran-Iraq warfare.

PMID- 28748327
TI  - Determination of Hopelessness and Quality of Life in Patients with Heart Disease:
      An Example from Eastern Turkey.
AB  - This descriptive study was undertaken in order to determine hopelessness and
      quality of life among the patients with heart disease. No sampling was made, and
      200 patients who were voluntary and were able to communicate were included in the
      study. The data of the study were collected using a personal information form
      that involved questions about patients' descriptive information and their
      diseases, Beck Hopelessness Scale and SF-36 Quality of Life Scale with a face-to
      face interview technique. For the analyses of the data, percentages, means, t
      test, Kruskal-Wallis and Pearson's correlation analyses were used. It was
      identified 54% of them was male patients. It was seen that there were significant
      between income status and general health perceptions, hopelessness; and between
      health perceptions and vitality, general health perceptions, global quality of
      life, hopelessness (p < .05). It was also explored that there was a negative
      correlation between hopelessness levels of the cardiac patients and functioning
      status, general health perceptions and global quality of life. It was determined
      that the desperation levels of the patients were above the middle level, and the
      quality of life was low.

PMID- 28748328
TI  - Potential therapeutic use of IL-37: a key suppressor of innate immunity and
      allergic immune responses mediated by mast cells.
AB  - The host response to either exogenous or endogenous insults produces a series of
      changes, characterized by alterations in immunological functions and generation
      of mediators called cytokines which include the interleukin-1 (IL-1) family
      members. IL-1 acts as a hormone mediating the host responses to infection and
      inflammation. Blocking inflammatory IL-1 family members can be effective against
      inflammatory disorders, including allergies. IL-37, (formerly IL-1 family member
      7), emerges as an inhibitor of innate and adaptive immunity by reducing
      circulating and organ cytokine levels. IL-37, mainly expressed in dendritic
      cells, monocytes, and plasma cells after TIR ligand activation, inhibits
      inflammatory cytokines and augments the level of anti-inflammatory IL-10. IL-37
      is involved in allergic reaction and its expression in dendritic cells causes
      tollerogenicity and inhibits inflammatory response. Mast cells (MCs) are
      ubiquitous in the body, reside in numerous mucosal tissues, and are mediators of
      allergic reaction, and innate and adaptive immunity. MCs are important regulators
      of cytokine generation in the course of inflammatory responses and allergy, and
      are implicated in the pathophysiology of allergic asthma. Cysteine protease
      caspase-1 activation leads to the cleavage of pro-form of IL-1 into active mature
      IL-1 which is present in stimulated and unstimulated inflammatory MCs.
      Inflammatory cytokine inhibition, along with the augmentation of anti
      inflammatory IL-10 by IL-37, is certainly beneficial and improves the
      pathogenesis of allergic disorders. However, in these studies, the exact
      mechanism(s) of IL-37-induced anti-inflammatory and anti-allergic activity along
      with its side effect(s) remain to be determined.

PMID- 28748329
TI  - Impact of Thiamethoxam on Honey Bee Queen (Apis mellifera carnica) Reproductive
      Morphology and Physiology.
AB  - High honey bee losses around the world have been linked in part by the regular
      use of neonicotinoids in agriculture. In light of the current situation, the aim
      of this study was to investigate the effects of thiamethoxam on the development
      of the reproductive system and physiology in the honey bee queen. Two
      experimental groups of honey bee queen larvae were treated with thiamethoxam
      during artificial rearing, applied via artificial feed in two cycles. In the
      first rearing cycle, honey bee larvae received a single treatment dose (4.28 ng
      thiamethoxam/queen larva on the 4th day after larvae grafting in artificial queen
      cells), while the second honey bee queen rearing cycle received a double
      treatment dose (total of 8.56 ng thiamethoxam/queen larva on the 4th and 5th day
      after larvae grafting in artificial queen cells). After emerging, queens were
      anesthetized and weighed, and after mating with drones were anesthetized,
      weighed, and sectioned. Ovary mass and number of stored sperm were determined.
      Body weight differed between untreated and treated honey bee queens. The results
      also show a decrease in the number of sperm within honey bee queen spermathecae
      that received the double thiamethoxam dose.

PMID- 28748330
TI  - An easily overlooked cause of toxic encephalopathy: methylene blue in a patient
      on an SSRI.

PMID- 28748331
TI  - Eligibility for phase 3 clinical trials of systemic therapy in real-world
      patients with metastatic renal cell cancer managed in a rural region.
AB  - Previous research has identified disparities between urban and rural cancer care,
      including clinical trial access. Therefore, we addressed three different
      questions in patients with metastatic renal cell cancer managed according to
      national guidelines in a rural Norwegian standard practice setting. (1) How many
      patients would have been eligible for three recent landmark randomized clinical
      trials? (2) Is survival different between eligible and non-eligible patients
      receiving first-line systemic therapy? (3) Is survival different between eligible
      patients and published trial results? We performed a retrospective analysis of
      101 consecutive patients (2006-2016). Only 52% of the patients were eligible for
      the first-line study of pazopanib versus sunitinib. The main reasons for
      violating inclusion or exclusion criteria were presence of brain metastases,
      absence of clear cell histology, and poor performance status. Even fewer patients
      were eligible for trials of nivolumab and cabozantinib in pre-treated patients.
      Eligible patients had significantly better survival than non-eligible patients,
      median 29.2 versus 8.5 months (p = 0.0001). These results confirm that many
      patients from rural practices do not fulfill all mandatory trial eligibility
      criteria. However, eligible patients managed according to national guidelines had
      survival outcomes in line with published first-line trial results.

PMID- 28748332
TI  - Demographic and Clinical Characteristics Associated with Engagement in Behavioral
      Health Treatment Among Children with Autism Spectrum Disorders.
AB  - This study investigates demographic and clinical factors associated with
      initiation, continuation, and adherence to behavioral health treatment (BHT)
      among children with autism spectrum disorder. Among 293 insured children referred
      for applied behavior analysis (ABA) based BHT, 23% never initiated treatment.
      Among those initiating treatment, 31% discontinued treatment within 1 year of
      treatment initiation, and only 15% received 80% or more of recommended treatment
      hours. Younger age at referral to treatment, private health insurance, and
      receiving more than 10 h/week of BHT were associated with treatment engagement.
      Co-occurring psychiatric and medical conditions were related to treatment
      discontinuation among children 5 years or older. These findings suggest specific
      subgroups that may benefit from additional support with engaging in recommended
      behavioral health treatment.

PMID- 28748333
TI  - Evaluation of Motor Skills in Children with Rubinstein-Taybi Syndrome.
AB  - Rubinstein-Taybi syndrome (RTS) is a rare genetic disease that associates
      intellectual disability with somatic characteristics. We have conducted a study
      of the overall motor abilities of RTS participants. Static postural performance
      as well as gait parameters were somewhat decreased, although not significantly
      compared to typically developing (TD) participants. In contrast, the motor skills
      requiring a high level of visuomotor coordination were considerably degraded in
      RTS participants compared to TD participants. We also found that cognitive status
      was significantly correlated with performance for tasks requiring a higher level
      of visuomotor coordination in RTS but not TD participants. Our study demonstrates
      a reduction in the motor performance of RTS participants and a link between the
      level of intellectual disability and motor capacities.

PMID- 28748334
TI  - Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers
      Exhibiting Autism Spectrum Disorder Symptoms.
AB  - Delayed language development may be an early indicator of autism spectrum
      disorder (ASD). Early intervention is critical for children with ASD, and the
      present study presents pilot data on a clinical trial of omega-3 and -6 fatty
      acid supplementation and language development, a secondary trial outcome, in
      children at risk for ASD. We randomized 31 children to receive an omega-3 and -6
      supplement or a placebo for 3 months, and measured their language abilities at
      baseline and after supplementation. Gesture use, but not word production,
      increased for children in the treatment group more than children in the placebo
      group. These results suggest possible effectiveness of omega-3 and -6
      supplementation for language development in children at risk for ASD.

PMID- 28748335
TI  - The Broader Autism Phenotype in Mothers is Associated with Increased Discordance
      Between Maternal-Reported and Clinician-Observed Instruments that Measure Child
      Autism Spectrum Disorder.
AB  - Autism spectrum disorder (ASD) diagnosis relies on parent-reported and clinician
      observed instruments. Sometimes, results between these instruments disagree. The
      broader autism phenotype (BAP) in parent-reporters may be associated with
      discordance. Study to Explore Early Development data (N = 712) were used to
      address whether mothers with BAP and children with ASD or non-ASD developmental
      disabilities were more likely than mothers without BAP to 'over-' or 'under
      report' child ASD on ASD screeners or interviews compared with clinician
      observation or overall impression. Maternal BAP was associated with a child
      meeting thresholds on a maternal-reported screener or maternal interview when
      clinician ASD instruments or impressions did not (risk ratios: 1.30 to 2.85).
      Evidence suggests acknowledging and accounting for reporting discordances may be
      important when diagnosing ASD.

PMID- 28748337
TI  - Response to letter to the editor "Prophylactic use of Bakri balloon for reduction
      of hemorrhage at cesarean for placenta previa: addition and clarification".

PMID- 28748336
TI  - Continuous release of oregano oil effectively and safely controls Varroa
      destructor infestations in honey bee colonies in a northern climate.
AB  - The ectoparasitic mite Varroa destructor is responsible for the death of millions
      of honey bee (Apis mellifera) colonies worldwide. Testing potential miticide
      compounds with different delivery methods that effectively control V. destructor
      and have low toxicity for honey bees is crucial to manage this parasite in hives.
      We determined the varroacide efficacy of three natural compounds delivered to
      hives with three application methods over a 4-week period. Oxalic acid in a
      sucrose solution was applied impregnated in cardboard (T1). A mixture of oregano
      and clove oils in an ethanol-gelatin solution was applied impregnated in
      absorbent pads (T2). Oregano oil alone was delivered using electric vaporizers
      (T3) to test the hypothesis that continuous release of miticides increases the
      varroacidal efficacy of essential oils. The varroa mite control rates for
      treatments T1-T3 were 76.5 +/- 7.11, 57.8 +/- 12.79 and 97.4 +/- 0.68%,
      respectively, and there were no differences for bee mortality between control and
      treatments 1 and 3. Additionally, most mites were killed in the first 2 weeks in
      T3 colonies compared to the last 2 weeks in colonies of the other treatments.
      These results demonstrate the importance of continuously releasing natural
      miticides to achieve safe and high rates of mite control in hives. They also show
      that oregano oil may be an effective miticide against V. destructor infestations
      in colonies.

PMID- 28748338
TI  - Prophylactic use of Bakri balloon for reduction of hemorrhage at cesarean for
      placenta previa: addition and clarification.

PMID- 28748339
TI  - Laparoscopic hysterectomy for benign indications: clinical practice guideline.
AB  - PURPOSE: Since the introduction of minimally invasive gynecologic surgery, the
      percentage of advanced laparoscopic procedures has greatly increased worldwide.
      It seems therefore, timely to standardize laparoscopic gynecologic care according
      to the principles of evidence-based medicine. With this goal in mind-the Dutch
      Society of Gynecological Endoscopic Surgery initiated in The Netherlands the
      development of a national guideline for laparoscopic hysterectomy (LH). This
      present article provides a summary of the main recommendations of the guideline.
      METHODS: This guideline was developed following the Dutch guideline of medical
      specialists and in accordance with the AGREE II tool. Clinically important issues
      were firstly defined and translated into research questions. A literature search
      per topic was then conducted to identify relevant articles. The quality of the
      evidence of these articles was rated following the GRADE systematic. An expert
      panel consisting of 18 selected gynecologists was consulted to formulate best
      practice recommendations for each topic. RESULTS: Ten topics were considered in
      this guideline, including amongst others, the different approaches for
      hysterectomy, advice regarding tissue extraction, pre-operative medical treatment
      and prevention of ureter injury. This work resulted in the development of a
      clinical practical guideline of LH with evidence- and expert-based
      recommendations. The guideline is currently being implemented in The Netherlands.
      CONCLUSION: A guideline for LH was developed. It gives an overview of best
      clinical practice recommendations. It serves to standardize care, provides
      guidance for daily practice and aims to guarantee the quality of LH at an
      (inter)national level.

PMID- 28748340
TI  - Inter-rater reliability and double reading analysis of an automated three
      dimensional breast ultrasound system: comparison of two independent examiners.
AB  - PURPOSE: Breast ultrasound could be a valuable tool complementary to mammography
      in breast cancer screening. Automated 3D breast ultrasound (ABUS) addresses
      challenges of hand-held ultrasound and could allow double reading analysis of
      ultrasound images. This trial assesses the inter-rater reliability and double
      reading analysis of an ABUS system. METHODS: To assess the reproducibility and
      diagnostic validity of the ABUS system, SomoVTM, a blinded double reading
      analysis, was performed in 1019 patients (2038 breasts) by two examiners
      (examiner A/B) and compared to single reading results, as well as to the
      reference standard regarding its diagnostic validity. Cohen's kappa coefficients
      were calculated to measure the inter-rater reliability and agreement of the
      different diagnostic modalities. Patient comfort and time consumption for image
      acquisition and reading were analyzed descriptively as secondary objectives.
      RESULTS: Analysis of inter-rater reliability yielded agreement in 81.6% (kappa =
      0.37; p < 0.0001) showing fair agreement. Single reading analysis of SomoVTM
      exams (examiner A/examiner B) compared to reference standard showed good
      specificity (examiner A: 88.3%/examiner B: 84.5%), fair inter-rater agreement
      (examiner A: kappa = 0.31/examiner B: kappa = 0.31), and adequate sensitivity
      (examiner A: 53.1%/examiner B: 64.2%). Double reading analysis yielded good
      sensitivity and specificity (73.7 and 77.7%). Mammography (n = 1911) alone
      detected 160 of 176 carcinomas (sensitivity 90.1%). Adding SomoVTM to mammography
      would have detected 12 additional carcinomas, resulting in a higher sensitivity
      of 97.7%. CONCLUSION: SomoVTM is a promising technique with good sensitivity,
      high patient comfort, and fair inter-examiner reliability. It allows double
      reading analysis that, in combination with mammography, could increase detection
      rates in breast cancer screening.

PMID- 28748341
TI  - Obstetric and perinatal outcomes among immigrant and non-immigrant women in
      Berlin, Germany.
AB  - BACKGROUND: In Germany, regular immigrants and their descendants have legal and
      financial access to health care equal to the general citizenry. Nonetheless, some
      of their health outcomes are comparatively unfavorable, and that is only
      partially explained by their lower socioeconomic status (SES). The aim of this
      study was to assess whether this disparity exists also for obstetric and
      perinatal outcomes. METHODS: We compared obstetric and perinatal outcomes between
      immigrant women (first or second generation) and non-immigrant women, delivering
      at three maternity hospitals in Berlin, Germany, 2011-2012. Multivariable
      logistic regression analysis was used to assess immigrant status and other
      possible risk factors for the baby being delivered preterm, small for gestational
      age (SGA), or transferred to neonatal care. RESULTS: The final database retained
      6702 women, of whom 53.1% were first- or second-generation immigrants. First
      generation Turkish immigrant women had significantly lower odds of preterm birth
      (OR 0.37, P < 0.001), SGA (OR 0.60, P = 0.0079), and transfer of the newborn to
      neonatal care (OR 0.61, P = 0.0034). Second-generation immigrant women had
      significantly lower odds of preterm birth (OR 0.67, P = 0.0049) or transfer of
      the newborn to neonatal care (OR 0.76, P = 0.0312). Moreover, women with
      education below university level, age 35+, or smokers had higher odds for poor
      outcomes. CONCLUSIONS: This study provides strong evidence that health
      disparities for obstetric and perinatal health outcomes do not exist in
      immigrants relative to native Germans, but exist instead in women without post
      secondary-level education compared to women with such education, regardless of
      ethnicity or migration history.

PMID- 28748342
TI  - Non-canonical IDH1 and IDH2 mutations: a clonal and relevant event in an Italian
      cohort of gliomas classified according to the 2016 World Health Organization
      (WHO) criteria.
AB  - According to the 2016 World Health Organization (WHO) classification of tumors of
      the central nervous system, assessment of exon 4 mutations in isocitrate
      dehydrogenase 1 or 2 genes (IDH1 or IDH2) is an essential step in the
      characterization of gliomas. The p.R132H mutation is the most frequent alteration
      in IDH genes, however other non-canonical IDH mutations can be identified. The
      aim of this study is to investigate in depth the prevalence of non-R132H IDH
      ("non-canonical") mutations in brain tumors classified according to the 2016 WHO
      scheme and their clonal distribution in neoplastic cells. A total of 288
      consecutive cases of brain gliomas (grade II-IV) were analyzed for exon 4 IDH1
      and IDH2 mutations. IDH1 and IDH2 analysis was performed using next generation
      sequencing. Non-canonical IDH mutations were identified in 13/52 (25.0%) grade II
      gliomas (astrocytomas: 8/31, 25.8%; oligodendrogliomas: 5/21, 23.8%) and in 5/40
      (12.5%) grade III gliomas (astrocytomas: 3/25, 12.0%; oligodendrogliomas: 2/15,
      13.3%). They were not identified in 196 grade IV gliomas (192 glioblastomas, 4
      gliosarcomas). In the large majority (>80%) of tumors IDH mutations, both IDH1
      R132H and the non-canonical ones, were present in the large majority (>80%) of
      neoplastic cells. Our data highlight the importance of investigating not only the
      IDH1-R132H mutation but also the non-canonical ones. These mutations are clonally
      distributed, with proportions of mutated neoplastic cells overlapping with those
      of p.R132H, a finding consistent with their driver role in gliomagenesis.

PMID- 28748343
TI  - A phase I/II study of gemcitabine during radiotherapy in children with newly
      diagnosed diffuse intrinsic pontine glioma.
AB  - The purpose of this phase I/II, open-label, single-arm trial is to investigate
      the safety, tolerability, maximum tolerated dose and preliminary efficacy of the
      potential radiosensitizer gemcitabine, administered concomitantly to
      radiotherapy, in children with newly diagnosed diffuse intrinsic pontine glioma
      (DIPG). Six doses of weekly gemcitabine were administered intravenously,
      concomitantly to 6 weeks of hyperfractionated radiotherapy. Successive cohorts
      received increasing doses of 140, 175 and 200 mg/m2 gemcitabine, respectively,
      following a 3 + 3 dose-escalation schedule without expansion cohort. Dose
      limiting toxicities (DLT) were monitored during treatment period. Clinical
      response was assessed using predefined case report forms and radiological
      response was assessed using the modified RANO criteria. Quality of life (QoL) was
      assessed using PedsQL questionnaires. Between June 2012 and December 2016, nine
      patients were enrolled. Treatment was well tolerated, and no DLTs were observed
      up to the maximum dose of 200 mg/m2. All patients experienced reduction of tumor
      related symptoms. QoL tended to improve during treatment. PFS and MOS were 4.8
      months (95% CI 4.0-5.7) and 8.7 months (95% CI 7.0-10.4). Classifying patients
      according to the recently developed DIPG survival prediction model, intermediate
      risk patients (n = 4), showed a PFS and MOS of 6.4 and 12.4 months, respectively,
      versus a PFS and MOS of 4.5 and 8.1 months, respectively, in high risk patient (n
      = 5). Gemcitabine up to 200 mg/m2/once weekly, added to radiotherapy, is safe and
      well tolerated in children with newly diagnosed DIPG. PFS and MOS were not
      significantly different from literature.

PMID- 28748344
TI  - Cigarette smoking-attributable burden of cancer by race and ethnicity in the
      United States.
AB  - PURPOSE: Cigarette smoking is the leading preventable cause of death and
      disability from cancer in the U.S. Smoking prevalence varies by racial and ethnic
      group, and therefore the smoking-related burden of cancer is expected to vary
      accordingly. METHODS: We estimated the cigarette smoking-attributable Disability
      Adjusted Life Years (DALYs) lost to cancer, overall and within racial/ethnic
      groups, using published DALY estimates, smoking prevalence from survey data, and
      relative risks from large cohort studies. RESULTS: In 2011, 2.6 million DALYs
      were lost to cancer due to cigarette smoking (27% of all DALYs lost to cancer).
      Smoking-attributable DALY rates were higher in men (968 per 100,000 people [95%
      confidence interval: 943-992]) than women (557 [540-574]). In combined sex
      analyses, DALY rates were higher in non-Hispanic Blacks (960 [934-983]) and non
      Hispanic Whites (786 [768-802]) than in Hispanics (409 [399-421]) and non
      Hispanic Asians (335 [320-350]). CONCLUSIONS: Smoking-attributable cancer burden
      was substantial in all racial and ethnic groups, underscoring the need for
      intensified tobacco cessation in all populations.

PMID- 28748345
TI  - Educational inequality in cancer mortality: a record linkage study of over 35
      million Italians.
AB  - PURPOSE: Large studies are needed to evaluate socioeconomic inequality for site
      specific cancer mortality. We conducted a longitudinal census-based national
      study to quantify the relative inequality in cancer mortality among educational
      levels in Italy. METHODS: We linked the 2011 Italian census with the 2012 and
      2013 death registries. Educational inequality in overall cancer and site-specific
      cancer mortality were evaluated by computing the mortality rate ratio (MRR).
      RESULTS: A total of 35,708,445 subjects aged 30-74 years and 147,981 cancer
      deaths were registered. Compared to the lowest level of education (none or
      primary school), the MRR for all cancers in the highest level (university) was
      0.57 (95% CI 0.55; 0.58) in men and 0.84 (95% CI 0.81; 0.87) in women. Higher
      education was associated with reduced risk of mortality from lip, oral cavity,
      pharynx, oesophagus, stomach, colon and liver in both sexes. Higher education
      (university) was associated with decreased risk of lung cancer in men (MRR: 0.43,
      95% CI 0.41; 0.46), but not in women (MRR: 1.00, 95% CI 0.92; 1.10). Highly
      educated women had a reduced risk of mortality from cervical cancer than lower
      educated women (MRR: 0.39, 95% CI 0.27; 0.56), but they had a similar risk for
      breast cancer (MRR: 1.01, 95% CI 0.94; 1.09). CONCLUSIONS: Education is inversely
      associated with total cancer mortality, and the association was stronger in men.
      Different patterns and trends in tobacco smoking in men and women account for at
      least most of the gender differences.

PMID- 28748346
TI  - Trends in incidence and tumour grade in screen-detected ductal carcinoma in situ
      and invasive breast cancer.
AB  - PURPOSE: In a biennial screening mammography programme, we analysed the trends in
      incidence of screen-detected DCIS and invasive breast cancers in the era of
      screen-film mammography (SFM) screening, the period of the transition to full
      field digital mammography (FFDM) screening and the period of FFDM screening. We
      also investigated a possible association between the incidence and grading of
      screen-detected DCIS and invasive breast cancer. METHODS: In the southern part of
      the Netherlands, FFDM screening gradually replaced SFM screening between May 2009
      and April 2010. We included a consecutive series of 484, 422 screens obtained
      between July 2005 and July 2015 and divided these screens into three groups; SFM
      only cohort, transition cohort and FFDM-only cohort. RESULTS: A total of 3059
      referred women were diagnosed with DCIS (n = 623) or invasive breast cancer (n =
      2436). The majority of DCIS were high-grade (48.2%), whereas the majority of the
      invasive breast cancers were low-grade (45.4%) or intermediate-grade (41.6%). The
      cancer detection rate (CDR) per 1000 screened women showed the same distribution
      by grade in both groups. The transition to FFDM was characterised by an increased
      overall detection rate of invasive cancers. CONCLUSIONS: Screening mammography
      detects mostly high-grade DCIS and low- or intermediate-grade invasive cancers.
      The grade distribution as well as the CDR in the years after the introduction of
      FFDM remained stable compared to the era of SFM screening. By diagnosing and
      treating high-grade DCIS, which otherwise may develop into high-grade invasive
      carcinoma, our findings provide new evidence for the beneficial value of
      screening mammography programmes.

PMID- 28748347
TI  - Molecular Basis of Pediatric Brain Tumors.
AB  - Brain tumors emerge as the second commonest type of pediatric solid tumors
      following hematologic malignancies. Genomic profiling of low- and high-grade
      gliomas, ependymomas and medulloblastomas has revealed chromosomal abnormalities
      and specific gene mutations which have been associated with aberrant activation
      of crucial signal transduction pathways, including mitogen-activated protein
      kinase, mammalian target of rapamycin and retinoblastoma tumor suppressor
      signaling. Furthermore, pediatric high-grade gliomas are associated with
      chromatin remodeling defects and somatic histone gene mutations that affect
      prognosis. This review provides an update of the molecular and genetic
      alterations that characterize pediatric brain tumors, and discusses novel
      therapeutic approaches targeting these abnormalities.

PMID- 28748348
TI  - Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical
      Outcomes in the Middle East and North Africa Region.
AB  - BACKGROUND: Genetic polymorphisms are known to influence outcomes with phenytoin
      yet effects in the Middle East and North Africa region are poorly understood.
      OBJECTIVES: The objective of this systematic review was to evaluate the impact of
      genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in
      populations originating from the Middle East and North Africa region, and to
      characterize genotypic and allelic frequencies within the region for genetic
      polymorphisms assessed. METHODS: MEDLINE (1946-3 May, 2017), EMBASE (1974-3 May,
      2017), Pharmacogenomics Knowledge Base, and Public Health Genomics Knowledge Base
      online databases were searched. Studies were included if genotyping and analyses
      of phenytoin pharmacokinetics were performed in patients of the Middle East and
      North Africa region. Study quality was assessed using a National Institutes of
      Health assessment tool. A secondary search identified studies reporting genotypic
      and allelic frequencies of assessed genetic polymorphisms within the Middle East
      and North Africa region. RESULTS: Five studies met the inclusion criteria.
      CYP2C9, CYP2C19, and multidrug resistance protein 1 C3435T variants were
      evaluated. While CYP2C9*2 and *3 variants significantly reduced phenytoin
      metabolism, the impacts of CYP2C19*2 and *3 variants were unclear. The multidrug
      resistance protein 1 CC genotype was associated with drug-resistant epilepsy, but
      reported impacts on phenytoin pharmacokinetics were conflicting. Appreciable
      variability in minor allele frequencies existed both between and within countries
      of the Middle East and North Africa region. CONCLUSIONS: CYP2C9 decrease-of
      function alleles altered phenytoin pharmacokinetics in patients originating from
      the Middle East and North Africa region. The impacts of CYP2C19 and multidrug
      resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical
      outcomes are unclear and require further investigation. Future research should
      focus on the clinical outcomes associated with phenytoin therapy. PROSPERO 2017:
      CRD42017057850.

PMID- 28748350
TI  - Expression of adenylate kinase fused MEK1R4F in Escherichia coli and its
      application in ERK phosphorylation.
AB  - OBJECTIVE: To construct a highly expressed and active MEK1R4F (a constitutively
      active form of mitogen-activated protein kinase kinase 1) by fusion of soluble
      adenylate kinase (Adk) tag, resulting in Adk-MEK1R4F protein suitable for
      preparation of phosphorylated ERK. RESULTS: We fused the Adk to the N-terminus of
      MEK1R4F through overlapping PCR. The expression of Adk-MEK1R4F fusion protein
      increased ~10-fold in Escherichia coli, and was purified to 95% via two
      purification steps including Ni-NTA and Q Sepharose fast flow (QFF)
      chromatography. The purified Adk-MEK1R4F protein was functional for ERK
      phosphorylation and could use ADP in addition to ATP. The Adk-MEK1R4F had higher
      catalytic activity than regular MEK1R4F both in vitro and in cell-free extracts
      system. CONCLUSIONS: Adenylate kinase was used as a soluble tag to facilitate
      MEK1R4F protein expression and its application in large-scale phosphorylated
      ERK1/2 preparation and purification.

PMID- 28748349
TI  - Desmoplastic small round cell tumor: evaluation of reverse transcription
      polymerase chain reaction and fluorescence in situ hybridization as ancillary
      molecular diagnostic techniques.
AB  - Desmoplastic small round cell tumor (DSRCT) is a rare, biologically aggressive
      soft tissue neoplasm of uncertain differentiation, most often arising in the
      abdominal and pelvic cavities of adolescents and young adults with a striking
      male predominance. Histologically, it is characterized by islands of uniform
      small round cells in prominent desmoplastic stroma, and it has a
      polyimmunophenotypic profile, typically expressing WT1 and cytokeratin, desmin,
      and neural/neuroendocrine differentiation markers to varying degrees. Tumors at
      other sites and with variant morphology are more rarely described. DSRCT is
      associated with a recurrent t(11;22)(p13;q12) translocation, leading to the
      characteristic EWSR1-WT1 gene fusion. Fluorescence in situ hybridization (FISH),
      to detect EWSR1 rearrangement, and reverse transcription-polymerase chain
      reaction (RT-PCR) to assess for EWSR1-WT1 fusion transcripts are routine
      diagnostic ancillary tools. We present a large institutional comparative series
      of FISH and RT-PCR for DSRCT diagnosis. Twenty-six specimens (from 25 patients)
      histologically diagnosed as DSRCT were assessed for EWSR1 rearrangement and EWSR1
      WT1 fusion transcripts. Of these 26 specimens, 24 yielded positive results with
      either FISH or RT-PCR or both. FISH was performed in 23 samples, with EWSR1
      rearrangement seen in 21 (91.3%). RT-PCR was performed in 18 samples, of which 13
      (72.2%) harbored EWSR1-WT1 fusion transcripts. The sensitivity of FISH in
      detecting DSRCT was 91.3%, and that of RT-PCR was 92.8% following omission of
      four technical failures. Therefore, both methods are comparable in terms of
      sensitivity. FISH is more sensitive if technical failures for RT-PCR are taken
      into account, and RT-PCR is more specific in confirming DSRCT. Both methods
      complement each other by confirming cases that the other method may not. In
      isolation, FISH is a relatively non-specific diagnostic adjunct due to the number
      of different neoplasms that can harbor EWSR1 rearrangement, such as Ewing
      sarcoma. However, in cases with appropriate morphology and a typical pattern of
      immunostaining, FISH is confirmatory of the diagnosis.

PMID- 28748351
TI  - Pig tissue factor pathway inhibitor alpha fusion immunoglobulin inhibits pig
      tissue factor activity in human plasma moderately more efficiently than the human
      counterpart.
AB  - OBJECTIVE: To determine the efficacy of soluble pig tissue factor pathway
      inhibitor fusion immunoglobulin (TFPI-Ig) in blocking pig to human xenogeneic
      blood coagulation. RESULTS: To generate pig TFPI-Ig or human TFPI-Ig, expression
      vector containing cDNA encoding pig TFPIalpha or human TFPIalpha combined with
      human constant Ig heavy chain region was cloned and introduced into CHO cells.
      After purification of pig TFPI-Ig and human TFPI-Ig, the inhibition of each
      recombinant protein on pig tissue factor (TF)-mediated blood coagulation was
      examined in human plasma. Compared to human TFPI-Ig, pig TFPI-Ig inhibited pig TF
      activity and thrombin generation in human plasma more efficiently at certain
      concentrations. CONCLUSIONS: Pig TFPI-Ig will be be useful as a therapeutic
      protein to treat pig to human xenogeneic blood coagulation.

PMID- 28748352
TI  - Thermostability enhancement of chitosanase CsnA by fusion a family 5 carbohydrate
      binding module.
AB  - OBJECTIVE: To determine the effects of carbohydrate-binding modules (CBMs) on the
      thermostability and catalytic efficiency of chitosanase CsnA. RESULTS: Three CBMs
      (BgCBM5, PfCBM32-2 and AoCBM35) were engineered at the C-terminus of chitosanase
      CsnA to create hybrid enzymes CsnA-CBM5, CsnA-CBM32 and CsnA-CBM35. K m values of
      all the hybrid enzymes were lower than that of the wild type (WT) enzyme;
      however, only CsnA-CBM5 had an elevated specific activity and catalytic
      efficiency. The fusion of BgCBM5 enhanced the thermostability of the enzyme,
      which exhibited a 8.9  degrees C higher T50 and a 2.9  degrees C higher Tm than
      the WT. Secondary structural analysis indicated that appending BgCBM5 at the C
      terminus considerably changed the secondary structure content. CONCLUSIONS: The
      fusion of BgCBM5 improved the thermal stability of CsnA, and the obtained hybrid
      enzyme (CsnA-CBM5) is a useful candidate for industrial application.

PMID- 28748353
TI  - miR-93 enhances hepatocellular carcinoma invasion and metastasis by EMT via
      targeting PDCD4.
AB  - OBJECTIVES: To clarify the potential biological function of miR-93 and its
      related molecular mechanism underlying metastasis in human hepatocellular
      carcinoma (HCC). RESULTS: miR-93 was significantly up-regulated in HCC tissues
      and was associated with poor 5-year overall survival in HCC patients. Transwell
      assays showed that over-expression of miR-93 increased HCC cell migration and
      invasion in vitro. Programmed cell death 4 (PDCD4) was a target gene of miR-93
      and miR-93 could down-regulate the expression of PDCD4 by directly targeting its
      3'-UTR. The re-expression of PDCD4 could attenuate the HCC cell invasion and
      migration induced by miR-93, while the knockdown of PDCD4 would promote HCC cell
      migration and invasion via the epithelial-mesenchymal transition (EMT) pathway.
      CONCLUSIONS: miR-93 provides new insight into the molecular mechanisms of
      pathogenesis and progression in HCC and offer a potential therapeutic target for
      the treatment of HCC patients.

PMID- 28748354
TI  - Pressure-Directed Embolization of Hepatic Arteries in a Porcine Model Using a
      Temporary Occlusion Balloon Microcatheter: Proof of Concept.
AB  - PURPOSE: The purpose of this project was to test the hypothesis that temporary
      hepatic artery balloon occlusion would favorably alter the distribution of
      particle emboli within the targeted and nontargeted downstream vascular
      compartments. MATERIALS AND METHODS: Five Yorkshire pigs underwent transfemoral
      placement of balloon microcatheters into selected segmental hepatic arteries. A
      collection catheter was surgically introduced into a downstream hepatic artery
      branch. Blood pressures at the femoral artery sheath and the collection catheter
      were obtained with the microcatheter balloon deflated and inflated. Identical
      quantities of calibrated 250- and 400-um microspheres were injected via the
      balloon microcatheter when inflated, then deflated. Each animal underwent up to
      four paired microsphere embolizations. Microspheres collected from the
      intrahepatic collection catheter were counted manually by light microscopy.
      RESULTS: Inflation of the balloon microcatheter in the segmental hepatic artery
      resulted in a consistent and significant decrease in blood pressure (mean: 30
      mmHg; range 23-43 mmHg; p < 0.05) in the downstream vascular compartment. The
      number of microspheres selectively delivered to the targeted intrahepatic
      collection catheter was significantly greater when the balloon microcatheter was
      inflated rather than deflated in all 20 paired embolic deliveries (by 2.4-fold,
      mean; p = 0.0002), despite delivery of the same total number of microspheres.
      CONCLUSION: Balloon occlusion significantly reduces blood pressure in the
      downstream vascular compartment, resulting in increased delivery of emboli to a
      targeted intrahepatic arterial collection catheter relative to other portions of
      the embolized vascular compartment, likely due to blood flowing into this
      compartment from neighboring hepatic and extrahepatic arteries.

PMID- 28748355
TI  - Retrospective comparison of S-1 plus cisplatin versus S-1 monotherapy for the
      treatment of advanced gastric cancer patients with positive peritoneal cytology
      but without gross peritoneal metastasis.
AB  - BACKGROUND: Peritoneal cytology positive for carcinoma cells (CY+) is an
      independent poor prognostic factor in gastric cancer, and patients with CY+ are
      diagnosed with stage IV disease. However, there is no standard treatment strategy
      for CY+ gastric cancer, whereas combination chemotherapy with fluoropyrimidine
      and platinum has been established as the standard treatment for unresectable
      advanced gastric cancer or after R2 resection. Herein, we assessed whether adding
      cisplatin to S-1 (SP) could improve the outcome of CY+ gastric cancer patients,
      as compared to S-1 monotherapy. METHODS: This retrospective study was conducted
      at a single Japanese institute between June 2005 and March 2014. Patients
      diagnosed with CY+ advanced gastric cancer and treated with S-1-based therapy
      were enrolled. Patients with incurable factors other than CY+ were excluded.
      RESULTS: Forty-four patients were enrolled; 25 and 19 were administered S-1 and
      SP, respectively. The 2-year survival rates were 52.0% [95% confidence interval
      (CI), 31.2-69.2%] and 52.6% (28.7-71.9%) in the S-1 and SP groups, respectively.
      The median overall survival (OS) and progression-free survival (PFS) were 28.2
      and 15.6 months in the S-1 group and 24.0 and 18.8 months in the SP group,
      respectively; they were not significantly different. The relative dose
      intensities were 0.79 (S-1) in the S-1 group and 0.69 (S-1)/0.70 (cisplatin) in
      the SP group. CONCLUSION: Adding cisplatin to long-term S-1 monotherapy did not
      significantly improve the outcome of CY+ advanced gastric cancer patients.

PMID- 28748357
TI  - Erratum to: Is Routine Preoperative Esophagogastroduodenoscopy Screening
      Necessary Prior to Laparoscopic Sleeve Gastrectomy? Review of 1555 Cases and
      Comparison with Current Literature.

PMID- 28748356
TI  - PD-L1 induced by IFN-gamma from tumor-associated macrophages via the JAK/STAT3
      and PI3K/AKT signaling pathways promoted progression of lung cancer.
AB  - BACKGROUND: Interferon-gamma (IFN-gamma) is conventionally regarded as an
      inflammatory cytokine that has a pivotal role in anti-infection and tumor immune
      surveillance. It has been used clinically to treat a variety of malignancies.
      However, increased evidence has suggested IFN-gamma can act to induce tumor
      progression. The role of IFN-gamma in regulating antitumor immunity appears to be
      complex and paradoxical. The mechanism underlying the dual aspects of IFN-gamma
      function in antitumor immunity is not clear. METHODS: (1) Lung cancer cells (A549
      cells) were cultured with pleural effusion or supernatant of tumor-associated
      macrophages (TAMs supernatant), and the expression levels of PD-L1 were detected
      by flow cytometer. The invasion capacity was measured in vitro using trans-well
      migration assays. (2) Pleural effusion mononuclear cells (PEMC) were separated by
      Ficoll Hypaque gradient. The expression of interleukin (IL)-6, IL-10, tumor
      necrosis factor (TNF)-alpha, and INF-gamma in the tumor-associated macrophages
      was analyzed by flow cytometry. (3) A549 cells were stimulated with IL-6, IL-10,
      TNF-alpha, or IFN-gamma and then the expression levels were detected by flow
      cytometry. (4) The expression levels of phospho-ERK (p-ERK), phospho-AKT (p-AKT),
      and phospho-Sat3 (p-Stat3) were analyzed with Western blot after stimulation with
      IFN-gamma. (5) Cotreatment of the A549 cells with MAPK/ERK-specific inhibitor
      PD98059, PI3K/AKT-specific inhibitor LY294002, or JAK/STAT3-specific inhibitor
      AG490, respectively, blocked IFN-gamma-induced PD-L1 expression, and then PD-L1
      expression was detected by flow cytometry. RESULTS: We demonstrated that TAMs
      could induce the expression of PD-L1 by the secretion of IFN-gamma through the
      Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3)
      signaling pathway and the phosphatidylinositol 3-kinase (PI3K)/AKT signaling
      pathway in A549 cells. Furthermore, the signal pathway blockers LY294002 or AG490
      could block the induced expression of PD-L1 by IFN-gamma. CONCLUSIONS: IFN-gamma
      was not always successful as an antitumor agent. It also can promote tumor cells
      to evade immune surveillance. Researchers should be cautious in using IFN-gamma
      as a therapeutic agent for cancer treatment.

PMID- 28748358
TI  - Extracellular electron transfer in acetogenic bacteria and its application for
      conversion of carbon dioxide into organic compounds.
AB  - Acetogenic bacteria (i.e., acetogens) produce acetate from CO2 during anaerobic
      chemoautotrophic growth. Because acetogens fix CO2 with high energy efficiency,
      they have been investigated as biocatalysts of CO2 conversion into valuable
      chemicals. Recent studies revealed that some acetogens are capable of
      extracellular electron transfer (EET), which enables electron exchange between
      microbial cells and extracellular solid materials. Thus, acetogens are promising
      candidates as biocatalysts in recently developed bioelectrochemical technologies,
      including microbial electrosynthesis (MES), in which useful chemicals are
      biologically produced from CO2 using electricity as the energy source. In
      microbial photoelectrosynthesis, a variant of MES technology, the conversion of
      CO2 into organic compounds is achieved using light as the sole energy source
      without an external power supply. In this mini-review, we introduce the general
      features of bioproduction and EET of acetogens and describe recent progress and
      future prospects of MES technologies based on the EET capability of acetogens.

PMID- 28748359
TI  - Analysis of medication errors at a large tertiary care hospital in Saudi Arabia:
      a retrospective analysis.
AB  - Background Medication errors (MEs) are common in health care settings and pose a
      threat for the hospitalized population. Therefore, aspects of MEs were explored
      in a tertiary setting serving a diverse population. Objective To examine the
      occurrence, severity and reporting of MEs in hospitalized patients. Methods This
      retrospective analysis included 10,683 ME report forms that were received by the
      Medication Safety Unit of King Saud Medical City (KSMC) in 2015. ME outcomes were
      determined according to the National Coordinating Council for Medication Error
      Reporting and Prevention (NCC MERP) Index for categorizing MEs algorithm. Results
      A total of 13,677 MEs in 912,500 prescriptions were reported. The incidence rate
      of MEs was 1.5% (13,677/912,500). The highest percentage (42.2%) of MEs occurred
      during the transcription stage, and 70.0% of MEs were reported as near misses.
      Wrong frequency and wrong concentration accounted for nearly half of the MEs.
      Conclusion We found 1.5 MEs per 100 prescriptions; more than two-thirds of the
      MEs were preventable and were intercepted before reaching the patients. Most MEs
      reported by pharmacists occurred at the transcription stage while wrong frequency
      was the most common error type encountered. Further studies should explore the
      clinical consequences of MEs at a healthcare institution.

PMID- 28748360
TI  - Autophagy and inflammation.
AB  - Autophagy is a homeostatic mechanism involved in the disposal of damaged
      organelles, denatured proteins as well as invaded pathogens through a lysosomal
      degradation pathway. Recently, increasing evidences have demonstrated its role in
      both innate and adaptive immunity, and thereby influence the pathogenesis of
      inflammatory diseases. The detection of autophagy machinery facilitated the
      measurement of autophagy during physiological and pathophysiological processes.
      Autophagy plays critical roles in inflammation through influencing the
      development, homeostasis and survival of inflammatory cells, including
      macrophages, neutrophils and lymphocytes; effecting the transcription, processing
      and secretion of a number of cytokines, as well as being regulated by cytokines.
      Recently, autophagy-dependent mechanisms have been studied in the pathogenesis of
      several inflammatory diseases, including infectious diseases, Crohn's disease,
      cystic fibrosis, pulmonary hypertension, chronic obstructive pulmonary diseases
      and so on. These studies suggested that modulation of autophagy might lead to
      therapeutic interventions for diseases associated with inflammation. Here we
      highlight recent advances in investigating the roles of autophagy in inflammation
      as well as inflammatory diseases.

PMID- 28748361
TI  - Case report of a novel nonsyndromic unilateral syndactyly of the hand.
AB  - Syndactyly is a cutaneous and/or bony digital malformation with possible webbing
      of adjacent fingers or toes and uni- or bilateral occurrence. We report an 84
      year old woman with a novel non-syndromic congenital malformation of her left
      hand. Clinical examination showed that she only had four digits. Radiograph of
      the hand revealed synostosis of the second and third proximal phalanx, resulting
      in a triangular shaped bone with relatively normal articulations at both ends.
      The phalangeal base of the fused finger tapers distally and is broader than the
      middle phalangeal bases of the ring and little finger. This malformation does not
      fit in any of the known types of syndromic or non-syndromic syndactylies. Our
      case report highlights that radiological imaging is crucial for identification of
      bony syndactyly and correct classification of a given syndactyly. Knowledge of
      the different types of syndactylies is important because certain malformations
      may occur as a defining part of a syndromic disease.

PMID- 28748362
TI  - Case study: failure of superior capsular reconstruction using dermal allograft.
AB  - Superior capsular reconstruction (SCR) is a novel technique for treating
      irreparable rotator cuff tears in younger patients in whom a reverse total
      shoulder arthroplasty is not the optimal treatment choice. This case study
      describes a middle-aged male with a recurrent, massive, irreparable rotator cuff
      tear treated with SCR that subsequently failed at the glenoid attachment. The
      patient underwent successful arthroscopic revision of the SCR. The case
      illustrates the MRI and arthroscopic correlations of the failed dermal allograft
      reconstruction, which to our knowledge has not been previously shown in the
      radiology literature.

PMID- 28748364
TI  - Saving Jobs that Save Lives.

PMID- 28748363
TI  - Type II sciatic nerve variant: an unexpected interventional hazard.
AB  - A 12-year-old girl presented with a 1-week history of right hip pain. MRI
      revealed a lesion in the incompletely fused posterior triradiate cartilage of the
      right acetabulum with imaging characteristics of an osteoid osteoma. The surgeon
      requested guidewire placement under CT guidance for lesion drilling. The CT
      approach was planned to avoid the usual course of the sciatic nerve, and the
      lesion was successfully removed and confirmed at histology to be an osteoid
      osteoma. At a follow-up visit, MRI showed no recurrence but demonstrated an
      abnormal common peroneal nerve from the sciatic notch to the popliteal fossa with
      denervation oedema in the tibias anterior and peroneal musculature. Review of the
      imaging showed a bifid piriformis muscle and type II sciatic nerve variant, with
      the common peroneal nerve component exiting the sciatic notch between the muscle
      bellies. The nerve's unexpected superolateral position placed it adjacent to the
      course of the guidewire, resulting in a presumed thermal injury at the time of
      drilling. This unusual case highlights the importance of the pre-procedural
      documentation of sciatic nerve variants in the planning of pelvic intervention.

PMID- 28748365
TI  - Urticaria and Angioedema: an Update on Classification and Pathogenesis.
AB  - Urticaria is a common, mast cell-driven disease presenting with wheals or
      angioedema or both. In the last years, urticaria has increasingly attracted
      notice to clinicians and researchers, last but not least inspired by the approval
      of omalizumab, an anti-IgE antibody, for urticaria treatment. There is wide
      consensus on the clinical classification based on duration and elicitation.
      However, the pathogenesis is incompletely understood. This review summarizes
      current guidelines for the management and novel insights in the pathogenesis of
      urticaria with special focus on their impact on clinical praxis. The
      classification of urticaria subgroups is mainly based on clinical criteria: acute
      and chronic urticaria (CU). Chronic urticaria comprises both chronic spontaneous
      urticaria (CSU) and chronic inducible urticaria (CIndU) that includes physical
      and non-physical urticarias. Recent research focused on characterizing the role
      of cells and mediators involved in the pathogenesis of urticaria, identifying the
      mechanisms of mast cell activation, and investigating underlying autoimmune
      processes in chronic spontaneous urticarial. Currently, non-sedating
      antihistamines and omalizumab, an antiimmunoglobulin E antibody, are recommended
      for the therapy of chronic urticaria, as both exhibit a favorable efficacy and
      safety profile. Novel therapeutic strategies aim at specifically targeting cells
      and mediators involved in the pathogenesis of urticaria.

PMID- 28748367
TI  - Commercial Online Social Network Data and Statin Side-Effect Surveillance: A
      Pilot Observational Study of Aggregate Mentions on Facebook.
AB  - INTRODUCTION: Surveillance of the safety of prescribed drugs after marketing
      approval has been secured remains fraught with complications. Formal
      ascertainment by providers and reporting to adverse-event registries, formal
      surveys by manufacturers, and mining of electronic medical records are all well
      known approaches with varying degrees of difficulty, cost, and success. Novel
      approaches may be a useful adjunct, especially approaches that mine or sample
      internet-based methods such as online social networks. METHODS: A novel
      commercial software-as-a-service data-mining product supplied by Sysomos from
      Datasift/Facebook was used to mine all mentions on Facebook of statins and stain
      related side effects in the US in the 1-month period 9 January 2017 through 8
      February 2017. RESULTS: A total of 4.3% of all 25,700 mentions of statins also
      mentioned typical stain-related side effects. Multiple methodological weaknesses
      stymie interpretation of this percentage, which is however not inconsistent with
      estimates that 5-20% of patients taking statins will experience typical side
      effects at some time. CONCLUSIONS: Future work on pharmacovigilance may be
      informed by this novel commercial tool, but the inability to mine the full text
      of a posting poses serious challenges to content categorization.

PMID- 28748368
TI  - Development and Evaluation of pH-Responsive Cyclodextrin-Based in situ Gel of
      Paliperidone for Intranasal Delivery.
AB  - Paliperidone (PLPD) is approved for treatment and management of schizophrenia.
      The current study demonstrates the potential of in situ gel of PLPD for nasal
      delivery. The permeation of drug through sheep nasal mucosa was analyzed since
      the nose-to-brain pathway has been indicated for delivering drugs to the brain.
      The carbopol 934 (CP)- and hydroxypropyl methyl cellulose K4M (HPMC)-based in
      situ gels containing 0.2% CP and 0.4% w/v HPMC were optimized using experimental
      design software. The use of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in nasal
      permeation of drug was investigated. Transmucosal permeation of PLPD was examined
      using sheep nasal mucosa. The in situ gels of PLPD exhibited satisfactory
      mucoadhesion and showed sustained drug release. The mucocilliary toxicity and
      histopathological examination confirmed that the nasal mucosa architecture
      remains unaffected after treatment with PLPD in situ gel. The formulation
      containing HP-beta-CD complex of PLPD exhibited higher rate of drug permeation
      through sheep nasal mucosa revealing the role of HP-beta-CD as nasal absorption
      enhancer. Thus, CP- and HPMC-based pH-triggered in situ gel containing HP-beta-CD
      drug inclusion complex demonstrates a novel nasal delivery of PLPD.

PMID- 28748366
TI  - Clinical Features of Psoriatic Arthritis: a Comprehensive Review of Unmet
      Clinical Needs.
AB  - Psoriatic arthritis (PsA) is a form of inflammatory arthritis (IA) affecting
      approximately 0.25% of the population. It is a heterogeneous disorder associated
      with joint damage, disability, disfiguring skin disease and in severe cases,
      premature mortality. Inherently irreversible and frequently progressive, the
      process of joint damage begins at, or before, the clinical onset of disease.
      Early recognition and intervention is thus crucial to patient outcome. At disease
      onset, however, PsA often resembles other forms of arthritis-especially
      rheumatoid arthritis (RA). Despite the similarities between PsA and RA, their
      distinctive pathologies require different treatments. For example, drugs that are
      effective in RA may not be effective in PsA and can even cause adverse effects.
      Since there is no currently validated test for PsA, the diagnosis is often missed
      or delayed and this has functional consequences for the patient. In the context
      of PsA and RA, making an accurate diagnosis is not the only challenge faced by
      rheumatologists. Choosing an effective and safe medication to manage the disease
      is another significant challenge and currently approximately 40% achieve
      meaningful responses such as minimal disease activity status. For the patient,
      several months may be lost as a result of trial and error testing-meanwhile,
      irreversible joint damage may occur. Clearly, more effective clinical tests are
      urgently needed to improve personalised patient care in PsA. Specifically, there
      is need to develop minimally invasive tests predictive of diagnosis, response to
      treatment and radiographic progression. In this review, we examined the biomarker
      development process, highlighted the importance of qualifying unmet clinical
      needs and emphasised the challenges that impede biomarker studies. We have
      compiled a comprehensive list of potentially clinically relevant biomarkers in
      PsA and provided a summary of proteomic technologies that might usefully support
      additional biomarker research in PsA.

PMID- 28748369
TI  - Classical experiments in whole-body metabolism: closed-circuit respirometry.
AB  - As part of a series of reviews aimed at providing historical context to the study
      of whole-body metabolism, this article focuses on the technique of closed-circuit
      respirometry. Developed by nineteenth century physiologists Henri-Victor Regnault
      and Jules de Reiset, a constant-pressure closed-circuit calorimeter capable of
      measuring oxygen consumption and carbon dioxide production in small animals
      became the framework for future experiments on whole-body metabolism in humans.
      The volume-loss and volume-replenishment techniques can be used to indirectly
      assess energy expenditure using an oxygen reservoir; spirometers are simplistic
      in design but difficult to operate. Leaks, calibration errors, equilibration of
      gases and dead space are some of the major limitations of the methodology.
      Despite operational difficulties, closed-circuit respirometry is highly accurate
      and reproducible. Due to the bespoke nature of many closed-circuit systems,
      maintenance and repair is often troublesome. Compounded by technological
      advancement, closed-circuit techniques have become progressively outdated.
      Nevertheless, the classical experiments in whole-body metabolism played a pivotal
      role in furthering our understanding of basic human physiology and paved the way
      for current methodologies used in the field.

PMID- 28748370
TI  - High-intensity aerobic interval training improves aerobic fitness and HbA1c among
      persons diagnosed with type 2 diabetes: considerations regarding HbA1c starting
      levels and intervention design.

PMID- 28748371
TI  - Acute effects of heated resistance exercise in female and male power athletes.
AB  - PURPOSE: To determine the effects of heated resistance exercise on thermal
      strain, neuromuscular function and hormonal responses in power athletes. METHODS:
      Sixteen (n = 8 female; 8 male) highly trained power athletes completed a combined
      strength and power resistance exercise session in hot (HOT ~30  degrees C) and
      temperate (CON ~20  degrees C) conditions. Human growth hormone (hGH), cortisol
      and testosterone concentrations in plasma, peak power (counter-movement jump,
      CMJ) and peak force (isometric mid-thigh pull) were measured before and after
      each training session; thermoregulatory responses were monitored during training.
      RESULTS: Skin temperature, thermal sensation and thermal discomfort were higher
      in HOT compared with CON. Sweat rate was higher in HOT for males only. Compared
      with CON, HOT had trivial effects on core temperature and heart rate. During HOT,
      there was a possible increase in upper-body power (medicine ball throw) in
      females [3.4% (90% CL -1.5, 8.6)] and males [(3.3% (-0.1, 6.9)], while lower-body
      power (vertical jump) was enhanced in males only [3.2% (-0.4, 6.9)]. Following
      HOT, CMJ peak power [4.4% (2.5; 6.3)] and strength [8.2% (3.1, 13.6)] were
      enhanced in female athletes, compared with CON, while effects in males were
      unclear. Plasma hGH concentration increased in females [83% (18; 183)] and males
      [107% (-21; 444)] in HOT compared with CON, whereas differential changes occurred
      for cortisol and testosterone. CONCLUSION: Heated resistance exercise enhanced
      power and increased plasma hGH concentration in female and males power athletes.
      Further research is required to assess the ergogenic potential of resistance
      exercise in the heat.

PMID- 28748372
TI  - Training and acute exercise modulates mitochondrial dynamics in football players'
      blood mononuclear cells.
AB  - PURPOSE: Regular physical activity induces oxidative stress but also causes
      adaptations in antioxidant defences including the nuclear factor kappaB (NF
      kappaB) pathway, which activates target genes related to antioxidant defences
      such as uncoupling proteins (UCPs), and mitochondrial biogenesis mediated by
      peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC
      1alpha). The aim of the study was to determine the effect of long-term training
      and acute exercise on oxidant/antioxidant status and the expression of
      mitochondrial biogenesis genes in peripheral blood mononuclear cells (PBMCs).
      METHODS: Twelve professional football players performed an 8-week exercise
      programme comprising a daily 2-h football training session. Blood samples were
      taken before and after the training season. RESULTS: The results reported a
      significant increase in antioxidant protein levels and in mitochondrial proteins
      in resting conditions after the 8-week training period. PGC1alpha, UCP-2 and
      mitofusin 2 protein levels also increased after acute exercise compared to pre
      exercise levels. After the training, the expression of PGC1alpha, cytochrome c
      oxidase subunit IV and mitochondrial NADH dehydrogenase subunit 5 messenger RNA
      (mRNA) significantly augmented after the acute physical activity compared to pre
      exercise levels; while no changes occurred in these mRNA in basal conditions. NF
      kappaB activation and ROS production reported a significant increase after acute
      exercise. CONCLUSIONS: Training increases the levels of proteins related to
      mitochondrial biogenesis and improves the antioxidant capabilities of
      mitochondria in PBMCs among well-trained football players. Acute exercise may act
      as an inducer of mitochondrial biogenesis through NF-kappaB activation and
      PGC1alpha gene expression.

PMID- 28748373
TI  - Novel combination of salinomycin and resveratrol synergistically enhances the
      anti-proliferative and pro-apoptotic effects on human breast cancer cells.
AB  - Resveratrol (RES) is a natural polyphenol having anti-proliferative activity
      against breast cancer cells. RES in combination with other chemo modulatory
      agents, minimizes toxicity and increases efficacy of the treatment. Salinomycin
      (SAL), a monocarboxylic polyether ionophore is known for selectively targeting
      breast cancer stem cells. Purpose of the present study was to investigate whether
      RES in combination with SAL exerts synergistic anti-proliferative activity on
      breast cancer cells. We further evaluated the molecular mechanism behind SAL and
      RES mediated cell death. Cytotoxicity assay was performed to determine 50%
      inhibitory concentration (IC50) of SAL and RES in different human breast cancer
      cells (HBCCs). Drug synergism and combination index (CI) were calculated using
      CompuSyn software and effects of synergistic combinations (CI < 1) involving
      lower doses of SAL and RES were selected for further studies. This combination
      significantly induced apoptosis in HBCCs without affecting non tumorigenic human
      breast epithelial cells MCF-10A. Co-treatment enhanced apoptosis in MCF-7 cells
      via reactive oxygen species (ROS) mediated mitochondrial dysfunction. Oxidative
      stress disrupt redox homeostasis which altered antioxidant enzymes viz. CuZn
      Superoxide dismutase (SOD), MnSOD and catalase. Additionally, combination altered
      nuclear morphology, enhanced PARP cleavage and led to caspase activation. SAL and
      RES also synergistically modulated MAPK pathway. Study suggests that SAL and RES
      offer a novel combination approach for the treatment of breast cancer.

PMID- 28748374
TI  - Alterations in amino acid levels in mouse brain regions after adjunctive
      treatment of brexpiprazole with fluoxetine: comparison with (R)-ketamine.
AB  - RATIONALE: Brexpiprazole, a serotonin-dopamine activity modulator, is approved in
      the USA as an adjunctive therapy to antidepressants for treating major depressive
      disorders. Similar to the N-methyl-D-aspartate receptor (NMDAR) antagonist
      ketamine, the combination of brexpiprazole and fluoxetine has demonstrated
      antidepressant-like effects in animal models of depression. OBJECTIVES: The
      present study was conducted to examine whether the combination of brexpiprazole
      and fluoxetine could affect the tissue levels of amino acids [glutamate,
      glutamine, gamma-aminobutyric acid (GABA), D-serine, L-serine, and glycine] that
      are associated with NMDAR neurotransmission. METHODS: The tissue levels of amino
      acids in the frontal cortex, striatum, hippocampus, and cerebellum were measured
      after a single [or repeated (14 days)] oral administration of vehicle, fluoxetine
      (10 mg/kg), brexpiprazole (0.1 mg/kg), or a combination of the two drugs.
      Furthermore, we measured the tissue levels of amino acids after a single
      administration of the NMDAR antagonist (R)-ketamine. RESULTS: A single injection
      of the combination of fluoxetine and brexpiprazole significantly increased GABA
      levels in the striatum, the D-serine/L-serine ratio in the frontal cortex, and
      the glycine/L-serine ratio in the hippocampus. A repeated administration of the
      combination significantly altered the tissue levels of amino acids in all
      regions. Interestingly, a repeated administration of the combination
      significantly decreased the D-serine/L-serine ratio in the frontal cortex,
      striatum, and hippocampus. In contrast, a single administration of (R)-ketamine
      significantly increased the D-serine/L-serine ratio in the frontal cortex.
      CONCLUSIONS: These results suggested that alterations in the tissue levels of
      these amino acids may be involved in the antidepressant-like effects of the
      combination of brexpiprazole and fluoxetine.

PMID- 28748375
TI  - Attenuation of ethanol abstinence-induced anxiety- and depressive-like behavior
      by the phosphodiesterase-4 inhibitor rolipram in rodents.
AB  - RATIONALE: Withdrawal symptoms stand as a core feature of alcohol dependence. Our
      previous results have shown that inhibition of phosphodiesterase-4 (PDE4)
      decreased ethanol seeking and drinking in alcohol-preferring rodents. However,
      little is known about whether PDE4 is involved in ethanol abstinence-related
      behavior. OBJECTIVE: The objective of this study was to characterize the role of
      PDE4 in the development of anxiety- and depressive-like behavior induced by
      abstinence from ethanol exposure in different animal models. METHODS: Using three
      rodent models of ethanol abstinence, we examined the effects of rolipram, a
      prototypical, selective PDE4 inhibitor, on (1) anxiety-like behavior induced by
      repeated ethanol abstinence in the elevated plus maze test in fawn-hooded
      (FH/Wjd) rats, (2) anxiety-like behavior in the open-field test and light-dark
      transition test following acute ethanol abstinence in C57BL/6J mice, and (3)
      anxiety- and depressive-like behavior induced by protracted ethanol abstinence in
      the elevated plus maze, forced-swim, and tail-suspension tests in C57BL/6J mice.
      RESULTS: Pretreatment with rolipram (0.1 or 0.2 mg/kg) significantly increased
      entries and time spent in the open arms of the elevated plus maze test in rats
      with repeated ethanol abstinence. Similarly, in mice with acute ethanol
      abstinence, administration of rolipram (0.25 or 0.5 mg/kg) dose-dependently
      increased the crossings in the central zone of the open-field test and duration
      and transitions on the light side of the light-dark transition test, suggesting
      anxiolytic-like effects of rolipram. Consistent with these, chronic treatment
      with rolipram (0.1, 0.3, or 1.0 mg/kg) increased entries in the open arms of the
      elevated plus maze test; it also reduced the increased duration of immobility in
      both the forced-swim and tail-suspension tests in mice after protracted ethanol
      abstinence, suggesting antidepressant-like effects of rolipram. CONCLUSIONS:
      These results provide the first demonstration for that PDE4 plays a role in
      modulating the development of negative emotional reactions associated with
      ethanol abstinence, including anxiety and depression. PDE4 inhibitors may be a
      novel class of drugs for treatment of alcoholism.

PMID- 28748376
TI  - Assessment of Gestational Diabetes and Associated Risk Factors and Outcomes in
      the Pacific Island Nation of Palau.
AB  - Objective Gestational diabetes mellitus (GDM) in Palau and across the Pacific
      Islands is a serious public health issue that is currently understudied. Methods
      This study was a retrospective cohort study that included 1730 women with a
      single live birth in Palau between January 2007 and December 2014. Results The
      overall prevalence of GDM among women in Palau was 5.5%. Women who were older
      (>=30 years) or obese (BMI >=30) were more likely to have GDM than women who were
      younger (<30 years) or non-obese (BMI <30), respectively. When adverse birth
      outcomes were assessed, women with GDM were found to have significantly higher
      prevalence of high birth weight infants, cesarean sections, and neonatal deaths
      when compared to women without GDM. In fact, women with GDM were five times more
      likely to have a neonatal death than women without GDM (p = 0.008). Conclusion
      Reducing overall rates of obesity in the population could help reduce rates of
      diabetes and GDM in Palau. Based on this work, current practices for the
      identification, monitoring and treatment of women with GDM should be evaluated
      and strengthened in order to reduce neonatal mortality rates in Palau.

PMID- 28748377
TI  - Microvascular effects of glucagon-like peptide-1 receptor agonists in type 2
      diabetes: a meta-analysis of randomized controlled trials.
AB  - AIMS: Results with GLP1-receptor agonists (GLP-1RA) on microvascular
      complications of diabetes are contrasting. In trials designed for cardiovascular
      outcomes, both liraglutide and semaglutide were associated with a relevant
      reduction in the incidence and progression of nephropathy. On the other hand, in
      the same trials, semaglutide was associated with an increased progression of
      retinopathy, and a similar trend was observed for liraglutide. This meta-analysis
      is aimed at assessing the effects of GLP-1RA on retinopathy and nephropathy.
      METHODS: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide,
      lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting
      all randomized clinical trials with a duration >11 weeks, enrolling patients with
      type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other
      non-GLP-1 receptor agonist drug. RESULTS: Of the 113 trials fulfilling the
      inclusion criteria, 78 and 62 did not report information on retinopathy and
      nephropathy, respectively. Treatment with GLP1-RA was not associated with a
      significant increase in the incidence of retinopathy (MH-OR [95% CI] 0.92 [0.74
      1.16]. p = 0.49). In subgroup analyses, GLP1-RA were associated with a lower risk
      of retinopathy in comparison with sulfonylureas. Cases of macular edema were
      reported only in nine trials with no sign of increased risk. GLP1-RA reduced the
      incidence of nephropathy with respect to comparators (MH-OR [95% CI] 0.74 [0.60
      0.92]. p = 0.005). This difference was significant versus placebo, but not versus
      any class of active comparators. CONCLUSIONS: GLP1-RA appear to reduce the
      incidence and/or progression of nephropathy and to have no specific effect on
      retinopathy-with the notable exception of semaglutide, which could have a
      negative impact on the retina.

PMID- 28748378
TI  - Validation of an Egyptian Arabic Version of Skindex-16 and Quality of Life
      Measurement in Egyptian Patients with Skin Disease.
AB  - PURPOSE: To translate and cross-culturally adapt the Skindex-16, a brief skin
      disease-specific QoL questionnaire, into Arabic for Egyptians and to evaluate its
      measurement properties in Egyptian patients with skin disease. METHOD:
      Translation and cultural adaption were performed following guidelines for cross
      cultural adaption of health-related quality of life measures. Subsequently,
      Skindex-16 was administered to 500 consecutive dermatological patients and 500
      healthy persons for verification of its reliability and validity. Next, we
      examined the effect of skin disorders on QoL as well as influences of age, sex,
      socioeconomic level, education, and use of medication on skin disease-related
      QoL. RESULTS: The instrument showed high internal consistency reliability and
      good construct and content validity. The quality of life was most deteriorated in
      the emotional domain followed by symptoms domain (mean percentage score 55.5 +/-
      23.1 and 31.7 +/- 26.8 respectively), while functioning was the least affected
      domain (mean percentage score 29.1 +/- 26.8). Higher total Skindex-16 scores were
      observed for patients with psoriasis, urticaria, acne, and atopic dermatitis than
      those with vitiligo and alopecia areata. Educational level, social class,
      medication use, and family history influenced the impact of skin disease on
      overall QoL. CONCLUSION: The adapted Egyptian Arabic version of Skindex-16 is
      valid and reliable; it showed that skin problems had a clinically significant
      impact on QoL in Egyptian patients.

PMID- 28748379
TI  - Focus Honoring Dr. Kristina "Kicki" Hakansson, Recipient of the 2016 Biemann
      Medal.

PMID- 28748380
TI  - Autologous bone marrow concentrate intradiscal injection for the treatment of
      degenerative disc disease with three-year follow-up.
AB  - PURPOSE: The purpose of this study is to assess safety and feasibility of
      intradiscal bone marrow concentrate (BMC) injections to treat low back discogenic
      pain as an alternative to surgery with three year minimum follow-up. METHODS: A
      total of 26 patients suffering from degenerative disc disease and candidates for
      spinal fusion or total disc replacement surgery were injected with 2 ml
      autologous BMC into the nucleus pulposus of treated lumbar discs. A sample
      aliquot of BMC was characterized by flow cytometry and CFU-F assay to determine
      progenitor cell content. Improvement in pain and disability scores and 12 month
      post-injection MRI were compared to patient demographics and BMC cellularity.
      RESULTS: After 36 months, only six patients progressed to surgery. The remaining
      20 patients reported average ODI and VAS improvements from 56.7 +/- 3.6 and 82.1
      +/- 2.6 at baseline to 17.5 +/- 3.2 and 21.9 +/- 4.4 after 36 months,
      respectively. One year MRI indicated 40% of patients improved one modified
      Pfirrmann grade and no patient worsened radiographically. Cellular analysis
      showed an average of 121 million total nucleated cells per ml, average CFU-F of
      2713 per ml, and average CD34+ of 1.82 million per ml in the BMC. Patients with
      greater concentrations of CFU-F (>2000 per ml) and CD34+ cells (>2 million per
      ml) in BMC tended to have significantly better clinical improvement. CONCLUSIONS:
      There were no adverse events related to marrow aspiration or injection, and this
      study provides evidence of safety and feasibility of intradiscal BMC therapy.
      Patient improvement and satisfaction with this surgical alternative supports
      further study of the therapy.

PMID- 28748381
TI  - Is it safe to perform lumbar spine surgery on patients over eighty five?
AB  - PURPOSE: The purpose of this study was to evaluate the safety and tolerance of
      lumbar spine surgery in patients over 85. MATERIALS AND METHODS: Patients over 85
      years of age with LSS who underwent decompression surgery with or without fusion
      between February 2011 and July 2014 were included. Comorbidities, autonomy
      (Activities of Daily Life and Braden scales), surgical parameters and
      complications (Clavien-Dindo classification) were collected. A telephone survey
      was performed to assess survival and patients' satisfaction at last follow-up.
      RESULTS: Mean follow-up was 27.4 +/- 7.6 months (range, 18-65). Mean age was 87.5
      +/- 2.7 years (range, 85-97). Mean ADLs and Braden scores were, respectively, 4.3
      +/- 1.2 and 20.2 +/- 1.4. Fifteen patients had associated spondylolisthesis.
      Nineteen minor complications (grade I and II, 38.7%), five moderate complications
      (grade III, 10.2%) and six major complications (grade IV and V, 12.2%) occurred.
      The perioperative mortality rate was 0.02%. At last follow-up, 41 patients were
      very satisfied (83.7%), five patients were satisfied (10.2%) and three patients
      were not satisfied (6.1%). Fusion did not affect the incidence of complications
      (p = 0.3) nor the average number of complications per patient (p = 0.2).
      CONCLUSION: Advanced age should not be a contraindication to lumbar spine surgery
      provided careful preoperative selection is performed. This study reported a high
      satisfaction rate and a low mortality rate at the price of a high number of
      complications, most of which being minor.

PMID- 28748382
TI  - Hydrogen-rich saline prevents bone loss in diabetic rats induced by
      streptozotocin.
AB  - PURPOSE: As an antioxidant molecule, hydrogen has been received much more
      attention and reported to be used as the treatment strategy for various diseases.
      In this study, we hypothesize that systemic delivery of hydrogen saline water may
      improve the reservation of bone tissue in the tibias and femurs of osteoporotic
      rats caused by diabetes mellitus (DM), which is characterized by increased levels
      of oxidative stress and overproducing reactive oxygen species (ROS). METHODS: The
      animals were divided into three groups of 12 animals and lavaged with normal
      saline (normal control and DM), or hydrogen saline water (DM + HRS). General
      status, blood glucose level, tibial and femoral mechanical strength, and micro-CT
      scans of the proximal tibia were recorded and analyzed. RESULTS: After 12 weeks,
      the glucose level was significantly decreased in the DM + HRS group compared with
      that of the DM group. Micro-CT scans showed that bone volume/total volume,
      connectivity density, trabecular thickness, and trabecular number were
      significantly increased compared with the DM group. Mechanical results of energy,
      stiffness and elastic modulus in the DM + HRS group were significantly higher
      than in the other groups for the tibia and femur. CONCLUSIONS: The results
      indicate that the systemic delivery of hydrogen saline water, which is safe and
      well tolerated, preserves bone volume and decreases fracture risks in
      streptozotocin-induced diabetic status rats, whose bone structure or inherent
      material properties of bone tissues are changed.

PMID- 28748383
TI  - Is ambient heat exposure levels associated with miscarriage or stillbirths in hot
      regions? A cross-sectional study using survey data from the Ghana Maternal Health
      Survey 2007.
AB  - It is well established that high ambient heat could cause congenital
      abnormalities resulting in miscarriage or stillbirth among certain species of
      mammals. However, this has not been systematically studied in real field settings
      among humans, despite the potential value of such knowledge for estimating the
      impact of global warming on the human species. This study sought to test the
      hypothesis that maternal heat exposure during pregnancy in hot regions is
      associated with increased prevalence of spontaneous abortions or stillbirths and
      to develop an analytical strategy to use existing data from maternal health
      surveys and existing data on historical heat levels at a geographic grid cell
      level. A subsample of the Ghana Maternal Health Survey 2007 was used in this
      study. This study sample consisted of 1136 women with pregnancy experiences
      between 2004 and 2007, out of which 141 women had a pregnancy that terminated in
      miscarriage or stillbirth. Induced-abortion cases were excluded. The linkage
      between ambient heat exposure and pregnancy outcome followed the epidemiological
      time-place-person principle, by linking timing of pregnancy outcome with
      historical data of local area heat levels for each month, as estimated in an
      international database. Maternal heat exposure level was estimated using
      calculated levels of the wet-bulb globe temperature (WBGT), which takes into
      account temperature, humidity, heat radiation, and air movement over the skin
      (wind speed). The values we used applied to exposure in the shade or in buildings
      without cooling (no solar heat radiation) and a standard air movement of 1 m/s.
      We applied two exposure durations: yearly average and monthly average for second
      month of pregnancy. In one analysis, we restricted the sample to four regions
      with time-homogeneous ambient heat. Analysis was made using logistic regression.
      About 12% of the latest pregnancies ended in either miscarriage (9.6%) or
      stillbirth (2.8%). The odds ratios indicated 12 to 15% increase (ORcrude 1.15,
      95% CI 0.92-1.42, and ORage adjusted 1.12, 95% CI 0.90-1.39) in the odds of
      having a stillbirth or miscarriage with each additional degree increase in WBGT,
      although this was just outside two-sided statistical significance. The WBGT range
      was quite narrow (most annual values in the range 24-26  degrees C, and most
      monthly values in the range 23-27  degrees C), which may have hidden any real
      impacts of high heat levels. The seemingly positive association observed
      disappeared after adjusting for gravidity. The analyses of the four selected
      regions indicated 27 to 42% increase in the odds of experiencing miscarriage or
      stillbirth with every degree increase in WBGT (crude OR 1.42 95% CI 1.00-2.03).
      This association remained after adjusting for maternal age pregnancy history,
      although no longer statistically significant (adjusted OR 1.27, 95% CI 0.89
      1.81). Environmental heat exposures may be associated with adverse pregnancy
      outcomes, but this study was inconclusive, possibly because the heat exposure
      range was small. Historical records of routine observations in existing databases
      can be used for epidemiological studies on the health effects of heat, although
      data from properly and purposively designed studies might be more suitable for
      further studies.

PMID- 28748384
TI  - The More Vivid the Imagination the Better: The Role of the Vividness of
      Imagination in Vasoconstriction Training and Vasodilatation Training.
AB  - Blood volume pulse biofeedback represents an effective non-pharmacological
      treatment for migraine. However, the underlying mechanisms of blood volume pulse
      biofeedback are still unclear. This study investigated the influence of vividness
      of imagination, private body consciousness, perfectionism, and general self
      efficacy on physiological (blood volume pulse amplitude) and psychological
      (session performance rated by participants and by trainers) success. Changes in
      skin conductance and skin temperature indicating habituation to training context
      were examined. Forty-five healthy male participants were randomized to four
      sessions of vasoconstriction training or vasodilatation training. Hierarchical
      linear models were estimated. Results showed significant changes of session
      performance rated by participants (UC = 0.62, p < .05), by trainers (UC = 0.52, p
      < .001), and skin temperature (UC = 0.01, p < .001) over time. A change of blood
      volume pulse amplitude could not be observed (UC = -0.01, p = .65). Vividness of
      imagination was highly important for both psychological achievement ratings (UC
      participants  = 1.3, p < .001; UC trainers  = 0.29, p < .01). Relations between
      skin temperature and general self-efficacy or personal standards were small (UC
      self-efficacy  = 0.002, p < .10; UC personal standards  = 0.002, p < .05). A time
      * group interaction regarding trainers' achievement ratings indicated a specific
      judgement effect. In conclusion, biofeedback trainers should pay attention to
      their beliefs and participants' vividness of imagination.

PMID- 28748385
TI  - Effect of implementation of guidelines on assessment and diagnosis of vertebral
      fractures in patients older than 50 years with a recent non-vertebral fracture.
AB  - : We evaluated the impact of a new Dutch guideline on systematic implementation
      of densitometric Vertebral Fracture Assessment (VFA) in patients with a recent
      non-vertebral fracture. Systematic implementation resulted in a significant
      increase of VFA, diagnosis of vertebral fractures (VFs), and percentage of
      patients eligible for treatment. INTRODUCTION: VFs are underdiagnosed although
      they are important predictors of fracture risk, independent of age and bone
      mineral density (BMD). The Dutch guideline on osteoporosis and fracture
      prevention recommends VFA in all patients aged >50 years with a recent non-VF.
      Our aim was to evaluate the effect of systematic implementation of densitometric
      VFA in patients with a recent non-VF at the fracture liaison service (FLS).
      METHODS: VFA was performed on lateral images of the spine using dual-energy X-ray
      absorptiometry (DXA) and graded according to Genant using Spine Analyzer
      software. RESULTS: We evaluated 582 patients before and 484 after implementation
      (mean age 67 and 66 years; 71 and 74% women, respectively). Performing VFA
      increased from 4.6 to 97.1% (p < 0.001) and the diagnosis of VFs from 2.2 to
      26.2% for grade >= 1 (p < 0.001) and from 0.9 to 14.7% for grade >= 2 (p <
      0.001). Prevalence of VFs increased with age (5.2% in 50-59-year olds to 27.8% in
      80+-year olds, p < 0.001), but was similar for both genders, non-VF locations,
      and BMD. Including patients with osteopenia and a VF increased the percentage of
      patients eligible for treatment by a quarter, from 31.0% in the pre-guideline to
      38.4% in the post-guideline cohort. CONCLUSIONS: Systematic guideline
      implementation resulted in a significant increase of VFA, diagnosis of VFs, and
      percentage of patients eligible for treatment. VFA contributes to documenting the
      high prevalence of VFs in patients visiting the FLS with a non-VF in both
      genders, at any age, non-VF location, and BMD.

PMID- 28748386
TI  - Effect of denosumab on trabecular bone score in postmenopausal women with
      osteoporosis.
AB  - : Trabecular bone score (TBS) assesses bone quality in the lumbar spine using
      dual-energy X-ray absorptiometry (DXA) scans. In postmenopausal women with
      osteoporosis, denosumab significantly improved TBS independently of bone mineral
      density (BMD). This practical technique may have a role in managing patients with
      osteoporosis. INTRODUCTION: TBS, a gray-level texture index determined from
      lumbar spine DXA scans, correlates with bone microarchitecture and enhances
      assessment of vertebral fracture risk independently of BMD. In the FREEDOM study,
      denosumab increased BMD and reduced new vertebral fractures in postmenopausal
      women with osteoporosis. This retrospective analysis explored the effect of
      denosumab on TBS and the association between TBS and BMD in FREEDOM. METHODS:
      Postmenopausal women with lumbar spine or total hip BMD T-score <-2.5 and -4.0 or
      higher at both sites received placebo or denosumab 60 mg subcutaneously every 6
      months. TBS indices were determined from DXA scans at baseline and months 12, 24,
      and 36 in a subset of 285 women (128 placebo, 157 denosumab) who had TBS values
      at baseline and >=1 postbaseline visit. RESULTS: Baseline characteristics were
      comparable between treatment groups; mean (SD) lumbar spine BMD T-score was -2.79
      (0.64), and mean (standard deviation [SD]) TBS was 1.200 (0.101) overall. In the
      placebo group, BMD and TBS increased by <=0.2% or decreased from baseline at each
      visit. In the denosumab group, progressive increases from baseline at 12, 24, and
      36 months were observed for BMD (5.7, 7.8, and 9.8%) and TBS (1.4, 1.9, and
      2.4%). Percentage changes in TBS were statistically significant compared with
      baseline (p < 0.001) and placebo (p <= 0.014). TBS was largely unrelated to BMD,
      regardless of treatment, either at baseline or for annual changes from baseline
      (all r 2 <= 0.06). CONCLUSIONS: In postmenopausal women with osteoporosis,
      denosumab significantly improved TBS independently of BMD.

PMID- 28748387
TI  - Costs of fragility hip fractures globally: a systematic review and meta
      regression analysis.
AB  - Purpose This study was conducted in order to systematically review the costs of
      hip fractures globally and identify drivers of differences in costs. Methods A
      systematic review was conducted to identify studies reporting patient level
      fragility hip fracture costs between 1990 and 2015. We extracted data on the
      participants and costs from these studies. Cost data concerning the index
      hospitalisation were pooled, and a meta-regression was used to examine its
      potential drivers. We also pooled data on the first-year costs following hip
      fracture and considered healthcare, social care as well as other cost categories
      if reported by studies. Results One hundred and thirteen studies reported costs
      of hip fracture based on patient level data. Patients developing complications as
      well as patients enrolled in intervention arms of comparative studies were found
      to have significantly higher costs compared to the controls. The pooled estimate
      of the cost for the index hospitalisation was $10,075. Health and social care
      costs at 12 months were $43,669 with inpatient costs being their major driver.
      Meta-regression analysis identified age, gender and geographic region as being
      significantly associated with the differences in costs for the index
      hospitalisation. Conclusion Hip fracture poses a significant economic burden and
      variation exists in their costs across different regions. We found that there was
      a considerable variation across studies in terms of study design, methodology,
      follow-up period, costs considered and results reported that highlights the need
      for more standardisation in this area of research.

PMID- 28748388
TI  - PLS3 sequencing in childhood-onset primary osteoporosis identifies two novel
      disease-causing variants.
AB  - : Altogether 95 children with primary bone fragility were screened for variants
      in PLS3, the gene underlying X-linked osteoporosis. Two children with multiple
      peripheral and spinal fractures and low BMD had novel disease-causing PLS3
      variants. Children with milder phenotypes had no pathogenic variants. PLS3
      screening is indicated in childhood-onset primary osteoporosis. INTRODUCTION: The
      study aimed to determine the role of pathogenic PLS3 variants in children's bone
      fragility and to elucidate the associated phenotypic features. METHODS: Two
      cohorts of children with bone fragility were screened for variants in PLS3, the
      gene underlying X-linked osteoporosis. Cohort I comprised 31 patients with
      childhood-onset primary osteoporosis of unknown etiology. Cohort II comprised 64
      children who had sustained multiple fractures but were otherwise healthy.
      Clinical and radiological data were reviewed. Peripheral blood DNA was Sanger
      sequenced for coding exons and flanking intronic regions of PLS3. RESULTS: In two
      patients of cohort I, where other common genetic causes had been excluded, we
      identified two novel disease-causing PLS3 variants. Patient 1 was a male with
      bilateral femoral fractures at 10 years, low BMD (Z-score -4.1; 18 years), and
      multiple vertebral compression fractures. He had a novel nonsense variant in
      PLS3. Patient 2 was a girl with multiple long bone and vertebral fractures and
      low BMD (Z-score -6.6 at 6 years). She had a de novo missense variant in PLS3;
      whole exome sequencing and array-CGH identified no other genetic causes. Iliac
      crest bone biopsies confirmed low-turnover osteoporosis in both patients. In
      cohort II, no pathogenic PLS3 variants were identified in any of the subjects.
      CONCLUSIONS: Two novel disease-causing variants in PLS3 were identified in a boy
      and a girl with multiple peripheral and spinal fractures and very low BMD while
      no pathogenic variants were identified in children with less severe skeletal
      fragility. PLS3 screening is warranted in male and female patients with childhood
      onset primary osteoporosis.

PMID- 28748389
TI  - Predisposing factors associated with atypical femur fracture among postmenopausal
      Korean women receiving bisphosphonate therapy: 8 years' experience in a single
      center.
AB  - : The risk factors for atypical femur fracture in patients exposed to
      bisphosphonates for at least 1 year were examined. Prolonged and continuous use
      of bisphosphonates, long-term use of glucocorticoids, and a higher body mass
      index were associated with increased risk of atypical femur fracture.
      INTRODUCTION: The purpose of the present study is to determine whether rheumatoid
      arthritis (RA) and other clinical factors are associated with an increased risk
      of bisphosphonate (BP)-related atypical femur fracture (AFF). METHODS: A
      retrospective nested case-control study of patients who had taken BPs for at
      least 1 year was conducted. Patients with AFF were identified by reviewing
      surgical and radiographic records. Three controls with no history of AFFs were
      randomly selected and age- and sex-matched to each patient with AFFs. Cox
      proportional hazard models were used to analyze the independent contribution of
      risk factors to BP-related AFF. RESULTS: Among the 35,104 patients prescribed BPs
      for at least 1 year, 43 females (mean age, 68 years) suffered AFFs (0.12%).
      Patients with AFFs were exposed to BPs for a mean of 7.3 years. Patients with
      AFFs were exposed to BPs for longer than those without AFFs and continued
      treatment without a drug holiday. More patients with AFF than controls had taken
      glucocorticoids and disease-modifying anti-rheumatic drugs. Multivariate Cox
      regression analyses estimated that long-term use of glucocorticoids, prolonged
      exposure to BP without cessation, and every 1 kg/m2 increase in the body mass
      index (BMI) increased the hazard ratio for AFFs by 3.0, 5.2, and 1.2,
      respectively. CONCLUSIONS: Prolonged and continuous use of BPs, long-term use of
      glucocorticoids, and a higher BMI increase the risk of AFFs. Switching long-term
      BP and glucocorticoid users to other bone-protective agents should be considered.

PMID- 28748390
TI  - miR-27b-3p, miR-181a-1-3p, and miR-326-5p are involved in the inhibition of
      macrophage activation in chronic liver injury.
AB  - : Macrophages are central players in inflammation, which leads to liver injury.
      It has been reported that continuous macrophage activation initiates this
      process. Our previous data show that the anti-inflammatory factor, 15-deoxy
      Delta12, 14-prostaglandin J2 (15d-PGJ2), inhibits bone marrow (BM)-derived
      macrophage (BMM) migration and inflammatory cytokine production. However, the
      underlying mechanism of 15d-PGJ2 inhibited BMM activation is still unclear. Here,
      we evaluate the role of 15d-PGJ2/PPARgamma axis in BMM activation. 15d-PGJ2
      reduced activated BMM population in injured livers. Inflammatory cytokine
      expressions (MIP-1beta, TNF-alpha, NOS2) were depressed by 15d-PGJ2 in
      macrophages isolated from treated livers. In vitro, 15d-PGJ2 inhibited BMM
      activation via PPARgamma. Moreover, miR-27b-3p, miR-181a-1-3p, and miR-326-5p
      target MIP-1beta, TNF-alpha, and NOS2 mRNA, respectively. The miRNA expressions
      were decreased in damaged livers, macrophages isolated from injured livers, and
      activated BMMs, which were renewed by 15d-PGJ2/PPARgamma axis. In activated BMMs,
      the miRNA inhibitors attenuated inhibitory effect of PPARgamma agonist
      (troglitazone or ciglitazone), while replenishing the lack of miRNAs induced by
      PPARgamma deficiency using miRNA mimics caused a decline of inflammatory
      cytokines. In conclusion, these data suggest that 15d-PGJ2/PPARgamma axis
      regulates BMM activation via promoting miR-27b-3p, miR-181a-1-3p, and miR-326-5p
      expressions. KEY MESSAGES: 15d-PGJ2 inhibits BMM activation via PPARgamma
      activation. 15d-PGJ2/PPARgamma axis promotes expression of miR-27b-3p, miR-181a-1
      3p, and miR-326-5p. miR-27b-3p, miR-181a-1-3p, and miR-326-5p have an inhibitory
      effect on BMM activation via 15d-PGJ2/PPARgamma axis.

PMID- 28748391
TI  - Social capital dynamics and health in mid to later life: findings from Australia.
AB  - PURPOSE: The influence of social capital has been shown to improve health and
      wellbeing. This study investigates the relationship between changes in social
      capital and health outcomes during a 6-year follow-up in mid to later life in
      Australia. METHODS: Nationally representative data from the Household, Income and
      Labour Dynamics in Australia (HILDA) survey included participants aged 45 years
      and over who responded in 2006, 2010 and 2012 (N = 3606). Each of the three
      components of social capital (connectedness, trust and participation) was
      measured in Waves 2006 and 2010 and categorised as: 'never low', 'transitioned to
      low', 'transitioned out of low' and 'consistently low'. Health outcomes in 2012
      included self-rated overall health, physical functioning, and mental health based
      on the Short Form 36-item health survey (SF-36). Multivariable logistic
      regression assessed changes in social capital (measured in 2006 and 2010)
      predicted poor health (measured in 2012), adjusting for covariates. RESULTS:
      Consistently low trust was significantly associated with higher odds of
      transitions into poor physical functioning (AOR 1.54; 95% Confidence Interval
      1.06-1.22), poor mental health (AOR 1.59; 95% CI 1.08-2.36) and poor self-rated
      health (AOR 1.86; 95% CI 1.27-2.72). Transition into low trust was also a
      predictor of poor self-rated health after adjusting for covariates (AOR 1.74; 95%
      CI 1.11-2.73). Changes in social connectedness in both directions (transitioned
      out of and into low) were statistically associated with poor self-rated health
      (AORs 1.40; 95% CI 1.00-1.97 and 1.61; 95% CI 1.11-2.34, respectively) after
      adjusting for confounders as well as other social capital components.
      CONCLUSIONS: Our longitudinal findings reveal social capital dynamics and effects
      on health in mid to later life. Social trust and connectedness could be important
      enablers for older persons to be more active in the community and potentially
      benefit their health and wellbeing over time.

PMID- 28748392
TI  - Mobile Monitoring of Traumatic Brain Injury in Older Adults: Challenges and
      Opportunities.

PMID- 28748393
TI  - The VALiDATe29 MRI Based Multi-Channel Atlas of the Squirrel Monkey Brain.
AB  - We describe the development of the first digital atlas of the normal squirrel
      monkey brain and present the resulting product, VALiDATe29. The VALiDATe29 atlas
      is based on multiple types of magnetic resonance imaging (MRI) contrast acquired
      on 29 squirrel monkeys, and is created using unbiased, nonlinear registration
      techniques, resulting in a population-averaged stereotaxic coordinate system. The
      atlas consists of multiple anatomical templates (proton density, T1, and T2*
      weighted), diffusion MRI templates (fractional anisotropy and mean diffusivity),
      and ex vivo templates (fractional anisotropy and a structural MRI). In addition,
      the templates are combined with histologically defined cortical labels, and
      diffusion tractography defined white matter labels. The combination of intensity
      templates and image segmentations make this atlas suitable for the fundamental
      atlas applications of spatial normalization and label propagation. Together, this
      atlas facilitates 3D anatomical localization and region of interest delineation,
      and enables comparisons of experimental data across different subjects or across
      different experimental conditions. This article describes the atlas creation and
      its contents, and demonstrates the use of the VALiDATe29 atlas in typical
      applications. The atlas is freely available to the scientific community.

PMID- 28748395
TI  - Variation in caries treatment proposals among dentists in Norway: the best
      interest of the child.
AB  - AIM: To explore variation in treatment-related-decisions for severe caries in
      children among dentists in the Public Dental Service (PDS) in Norway. It was also
      to evaluate the treatment choices in relation to the best interest of children
      and a child's rights to enjoy the highest standard of health care. METHODS: A pre
      coded questionnaire was sent electronically to all general dental practitioners
      (GDPs) working in the PDS in eight counties in Norway (n = 611). The
      questionnaire included two case scenarios to reflect common dental conditions
      related to severe caries among 5-year-old children. Paediatric dentists and
      paediatric students were invited to validate the different treatment options.
      Frequency distributions and statistical analyses were carried out using Chi
      square statistics. RESULTS: The response rate was 65% (n = 391) among the GDPs. A
      majority of the GDPs preferred a new appointmentwith behaviour management
      techniques (BMT) to a child presenting pulpitis and pain. Dentists educated
      outside the Nordic region would use restraint more often as a treatment
      alternative when the child was in pain than Nordic-educated dentists (p?0.05).
      Dentists with less  than 10 years of experience preferred BMT and sedation more
      often when the child was in pain than their older colleagues, who, however,
      preferred a waiting approach and no immediate treatment if the child was not in
      pain(p?0.05) [corrected]. CONCLUSIONS: Use of BMT and sedation is related to
      region of education and years of experience. Awareness of ethical principles with
      the child's best interest in mind, should receive increased attention.

PMID- 28748394
TI  - Association mapping analysis of fiber yield and quality traits in Upland cotton
      (Gossypium hirsutum L.).
AB  - Fiber yield and quality are the most important traits for Upland cotton
      (Gossypium hirsutum L.). Identifying high yield and good fiber quality genes are
      the prime concern of researchers in cotton breeding. Association mapping offers
      an alternative and powerful method for detecting those complex agronomic traits.
      In this study, 198 simple sequence repeats (SSRs) were used to screen markers
      associated with fiber yield and quality traits with 302 elite Upland cotton
      accessions that were evaluated in 12 locations representing the Yellow River and
      Yangtze River cotton growing regions of China. Three subpopulations were found
      after the estimation of population structure. The pair-wise kinship values varied
      from 0 to 0.867. Only 1.59% of the total marker locus pairs showed significant
      linkage disequilibrium (LD, p < 0.001). The genome-wide LD decayed within the
      genetic distance of ~30 to 32 cM at r 2 = 0.1, and decreased to ~1 to 2 cM at r 2
      = 0.2, indicating the potential for association mapping. Analysis based on a
      mixed linear model detected 57 significant (p < 0.01) marker-trait associations,
      including seven associations for fiber length, ten for fiber micronaire, nine for
      fiber strength, eight for fiber elongation, five for fiber uniformity index, five
      for fiber uniformity ratio, six for boll weight and seven for lint percent, for a
      total of 35 SSR markers, of which 11 markers were associated with more than one
      trait. Among marker-trait associations, 24 associations coincided with the
      previously reported quantitative trait loci (QTLs), the remainder were newly
      identified QTLs/genes. The QTLs identified in this study will potentially
      facilitate improvement of fiber yield and quality in the future cotton molecular
      breeding programs.

PMID- 28748396
TI  - Disagreement between the results from three commercial tests for the detection of
      Borrelia-specific serum antibodies in the Netherlands associated with antibiotic
      treatment for Lyme borreliosis: a retrospective study.
AB  - The diagnosis of Lyme borreliosis is challenging because of the often non
      specific symptoms and persisting antibodies after infection. We investigated the
      diagnostic characteristics of two enzyme-linked immunosorbent assays (ELISAs) and
      an immunoblot for the detection of Borrelia-specific serum antibodies using
      different test strategies in individuals with and without antibiotic treatment
      for Lyme borreliosis. This retrospective study included healthy individuals,
      patients with active Lyme neuroborreliosis and patients treated for Lyme
      neuroborreliosis. Two ELISAs were compared: the C6 ELISA and the SERION ELISA.
      Equivocal and positive results were confirmed by immunoblot. We included 174
      healthy individuals, of whom 27 (15.5%) were treated for Lyme borreliosis in the
      past, 36 patients were treated for Lyme neuroborreliosis and 27 patients had
      active Lyme neuroborreliosis. All the active Lyme neuroborreliosis patients were
      reactive in both ELISAs (100% sensitivity); less reactivity was seen in the other
      three groups (range 17.7% to 69.4%). The concordance between the ELISA results
      was high in active Lyme neuroborreliosis patients (26/27; 96.3%) and healthy
      individuals (131/147; 89.1%), but lower in treated healthy individuals (18/27;
      66.7%) and treated Lyme neuroborreliosis patients (18/36; 50.0%) (p <= 0.005).
      This study showed that antibiotic treatment against Lyme borreliosis was strongly
      associated with discordant ELISA and test strategy results (odds ratio: 10.52; p
      < 0.001 and 9.98; p = 0.014, respectively) suggesting antibiotic treatment
      influences the pace at which the various antibodies directed to the different
      antigens used in both ELISAs wane. Among treated neuroborreliosis patients, the
      SERION ELISA stayed positive for a longer period after infection compared to the
      C6 ELISA. This should be taken into consideration when requesting and/or
      interpreting Lyme serology.

PMID- 28748397
TI  - Activity of the novel siderophore cephalosporin cefiderocol against multidrug
      resistant Gram-negative pathogens.
AB  - The novel siderophore cephalosporin cefiderocol (S-649266) with potent activity
      against Gram-negative pathogens was recently developed (Shionogi & Co., Ltd.).
      Here, we evaluated the activity of this new molecule and comparators against a
      collection of previously characterized Gram-negative isolates using broth
      microdilution panels. A total of 753 clinical multidrug-resistant Gram-negative
      isolates collected from hospitals worldwide were tested against cefiderocol and
      antibiotic comparators (ceftolozane-tazobactam [CT], meropenem [MEM], ceftazidime
      [CAZ], ceftazidime-avibactam [CZA], colistin [CST], aztreonam [ATM], amikacin
      [AMK], ciprofloxacin [CIP], cefepime [FEP], and tigecycline [TGC]) for their
      susceptibility. The collection included Escherichia coli (n = 164), Klebsiella
      pneumoniae (n = 298), Enterobacter sp. (n = 159), Pseudomonas aeruginosa (n =
      45), and Acinetobacter baumannii (n = 87). Resistance mechanisms included
      producers of carbapenemases and extended-spectrum beta-lactamases (ESBLs). In
      addition, a series of colistin-resistant enterobacterial isolates (n = 74),
      including 15 MCR-1 producers, were tested. The MIC90 of cefiderocol was 2 mg/L,
      while those of comparative drugs were >64 mg/L for CT, MEM, CAZ, CZA, and AMK,
      >32 mg/L for ATM, >16 mg/L for FEP, 8 mg/L for CST, and 2 mg/L for TGC. The MIC50
      of cefiderocol was 0.5 mg/L, while those of other drugs were >64 mg/L for CAZ, 64
      mg/L for CT, >32 mg/L for ATM, >16 mg/L for FEP, 8 mg/L for MEM and AMK, >4 mg/L
      for CIP, 1 mg/L for CZA, 0.5 mg/L for TGC, and <0.5 mg/L for CST. Only 20 out of
      753 strains showed MIC values of cefiderocol >=8 MUg/mL. Compared to the other
      drugs tested, cefiderocol was more active, with the exception of colistin and
      tigecycline showing equivalent activity against certain subgroups of bacteria.

PMID- 28748398
TI  - Intranasal Delivery of Topically-Acting Levofloxacin to Rats: a Proof-of-Concept
      Pharmacokinetic Study.
AB  - PURPOSE: To evaluate the potential of levofloxacin intranasal administration as a
      promising alternative approach to treat local infections such as chronic
      rhinosinusitis, by delivering drug concentrations directly to the site of
      infection. METHODS: Drug concentrations were measured in plasma, olfactory bulb
      and nasal mucosa of anterior (ANM) and posterior regions after intranasal (0.24
      mg/kg) and intravenous (10 mg/kg) administration to rats, and pharmacokinetic
      parameters were compared between routes. For intranasal administration a
      thermoreversible in-situ gel was used. RESULTS: Plasma and olfactory bulb
      exposure to levofloxacin was minimal following intranasal dose, preventing
      systemic and central nervous system adverse effects. Levofloxacin concentration
      time profile in ANM revealed higher concentrations during the first 60 min of the
      study following intranasal administration than the corresponding ones obtained
      after intravenous administration. A rapid and continuous decay of levofloxacin
      concentration in this nasal region was observed after intranasal delivery,
      resulting in much lower values at the last sampling time-points. CONCLUSION: The
      higher dose-normalized concentrations and pharmacokinetic exposure parameters of
      levofloxacin in ANM after intranasal administration, demonstrates that intranasal
      delivery of the formulated gel is, by itself, advantageous for delivering
      levofloxacin to biophase and thus an attractive approach in management of chronic
      rhinosinusitis.

PMID- 28748399
TI  - Delafloxacin: First Global Approval.
AB  - Delafloxacin (BaxdelaTM) is a fluoroquinolone antibacterial with activity against
      both gram-positive and gram-negative pathogens being developed by Melinta
      Therapeutics. The drug is being investigated or considered as a treatment for
      various bacterial infections and in June 2017 received approval in the USA for
      the treatment of acute bacterial skin and skin structure infections. This article
      summarizes the milestones in the development of delafloxacin leading to this
      first global approval for the treatment of acute bacterial skin and skin
      structure infections.

PMID- 28748400
TI  - Reconstructing Genetic Regulatory Networks Using Two-Step Algorithms with the
      Differential Equation Models of Neural Networks.
AB  - BACKGROUND: The identification of genetic regulatory networks (GRNs) provides
      insights into complex cellular processes. A class of recurrent neural networks
      (RNNs) captures the dynamics of GRN. Algorithms combining the RNN and machine
      learning schemes were proposed to reconstruct small-scale GRNs using gene
      expression time series. RESULTS: We present new GRN reconstruction methods with
      neural networks. The RNN is extended to a class of recurrent multilayer
      perceptrons (RMLPs) with latent nodes. Our methods contain two steps: the edge
      rank assignment step and the network construction step. The former assigns ranks
      to all possible edges by a recursive procedure based on the estimated weights of
      wires of RNN/RMLP (RERNN/RERMLP), and the latter constructs a network consisting
      of top-ranked edges under which the optimized RNN simulates the gene expression
      time series. The particle swarm optimization (PSO) is applied to optimize the
      parameters of RNNs and RMLPs in a two-step algorithm. The proposed RERNN-RNN and
      RERMLP-RNN algorithms are tested on synthetic and experimental gene expression
      time series of small GRNs of about 10 genes. The experimental time series are
      from the studies of yeast cell cycle regulated genes and E. coli DNA repair
      genes. CONCLUSION: The unstable estimation of RNN using experimental time series
      having limited data points can lead to fairly arbitrary predicted GRNs. Our
      methods incorporate RNN and RMLP into a two-step structure learning procedure.
      Results show that the RERMLP using the RMLP with a suitable number of latent
      nodes to reduce the parameter dimension often result in more accurate edge ranks
      than the RERNN using the regularized RNN on short simulated time series.
      Combining by a weighted majority voting rule the networks derived by the RERMLP
      RNN using different numbers of latent nodes in step one to infer the GRN, the
      method performs consistently and outperforms published algorithms for GRN
      reconstruction on most benchmark time series. The framework of two-step
      algorithms can potentially incorporate with different nonlinear differential
      equation models to reconstruct the GRN.

PMID- 28748401
TI  - System Biology Approach to Identify Potential Receptor for Targeting Cancer and
      Biomolecular Interaction Studies of Indole[2,1-a]Isoquinoline Derivative as
      Anticancerous Drug Candidate Against it.
AB  - Cancer is a public health concern which is spreading throughout the world.
      Different approaches have been employed to combat this disease. System biology
      approach has been used to understand the molecular mechanisms of drugs targeting
      cancer cell's receptor which have opened-up a window to develop effective drugs
      for it. We have demonstrated biomolecular interaction studies using the rational
      drug design of indole[2,1-a]isoquinoline derivative as a potent inhibitor against
      identified cancerous protein PIK3CA -a catalytic sub-unit of PI3K family protein
      and compared its affinity with FDA approved drugs for receptors such as
      dactolisib, idelalisib, and several others such afatinib, avastin, ceritinib and
      crizotinib, etc.; by docking against potential receptor to set a cutoff value for
      our screening. Isoquinolines are small alkaloids with a vast variety of
      substitution depending upon their biogenetic pattern. Isoquinoline derivatives
      have been reported for their antimalarial, antibacterial, antifungal and
      anticancerous activities. The results obtained from the present studies conclude
      that membrane protein is an efficient drug that can be used to target cancer.
      Moreover, comparative study with ADMET prediction concludes that isoquinoline can
      be a potent drug for cancer treatment.

PMID- 28748402
TI  - Methodology for the identification of vulnerable asylum seekers.
AB  - Asylum seekers often experience situations of vulnerability, being frequently
      exposed to a heightened risk of harm, and thus require special care, support and
      protection. The categories of "vulnerable persons", identified by International
      Legislation, and an individual's classification as a "vulnerable asylum seeker",
      have important implications in the reception procedures, in the decision-making
      phase and in the definition of therapeutic needs and rehabilitation. The Istanbul
      Protocol, the first international guideline approved by the United Nations and
      applied in different contexts, is not applicable for the assessment of the
      totality of the conditions (medical and otherwise), and therefore, the
      identification and assessment of conditions of vulnerability is largely delegated
      to questionnaires administered by non-medical personnel. The proposed
      methodology, based on the modificatory reworking of the Guidelines of the
      International Academy of Legal Medicine concerning the "medicolegal ascertainment
      of personal injury and damage on the living person", takes into consideration all
      the medical issues relevant for the decision concerning the applicant, both in
      the reception procedures and in the outcome of the asylum application.

PMID- 28748403
TI  - Evaluation of InnoTyper(r) 21 in a sample of Rio de Janeiro population as an
      alternative forensic panel.
AB  - The use of bi-allelic markers such as retrotransposable element insertion
      polymorphisms or Innuls (for insertion/null) can overcome some limitations of
      short tandem repeat (STR) loci in typing forensic biological evidence. This study
      investigated the efficiency of the InnoTyper(r) 21 Innul markers in an urban
      admixed population sample in Rio de Janeiro (n = 40) and one highly compromised
      sample collected as evidence by the Rio de Janeiro police. No significant
      departures from Hardy-Weinberg equilibrium were detected after the Bonferroni
      correction (alpha' ~ 0.05/20, p < 0.0025), and no significant linkage
      disequilibrium was observed between markers. Assuming loci independence, the
      cumulative random match probability (RMP) was 2.3 * 10-8. A lower mean Fis value
      was obtained for this sample population compared with those of three North
      American populations (African-American, Southwest Hispanic, US Caucasian).
      Principal component analysis with the three North American populations and one
      from 21 East Asian population showed that African Americans segregated as an
      independent group while US Caucasian, Southwest Hispanic, East Asian, and Rio de
      Janeiro populations are in a single large heterogeneous group. Also, a full
      Innuls profile was produced from an evidence sample, despite the DNA being highly
      degraded. In conclusion, this system is a useful complement to standard STR kits.

PMID- 28748404
TI  - Necrotic and apoptotic cell death induced by Captan on Saccharomyces cerevisiae.
AB  - Captan is one of the most widely used broad-spectrum fungicide applied to control
      several early and late diseases of grapes, apples, and other fruits and
      vegetables, and as other phthalimide fungicides is defined as a multisite
      compound with thiol-reactivity. Captan can affect non-target organisms as yeasts,
      modifying microbial populations and fermentation processes. In this study, we
      asked whether Captan thiol-reactivity and other mechanisms are involved in acute
      Captan-induced cell death on aerobic growing Saccharomyces cerevisiae. Thus for,
      we analyze cellular protein and non-protein thiols, cell membrane integrity,
      reactive oxygen species accumulation, phosphatidylserine externalization, and
      apoptotic mutants behavior. The results showed that when submitted to acute
      Captan treatment most cells lost their membrane integrity and died by necrosis
      due to Captan reaction with thiols. However, part of the cells, even maintaining
      their membrane integrity, lost their culture ability. These cells showed an
      apoptotic behavior that may be the result of non-protein thiol depletion and
      consequent increase of reactive oxygen species (ROS). ROS accumulation triggers a
      metacaspase-dependent apoptotic cascade, as shown by the higher viability of the
      yca1-deleted mutant. Together, necrosis and apoptosis are responsible for the
      high mortality detected after acute Captan treatment of aerobically growing cells
      of S. cerevisiae.

PMID- 28748405
TI  - The Burden of Chronic Urticaria from Brazilian Patients' Perspective.
AB  - INTRODUCTION: Chronic urticaria (CU), a proxy for chronic spontaneous urticaria,
      has been associated with a negative impact on health-related quality of life
      (HRQoL) and costs, but there is limited evidence on the burden of CU in Brazil.
      The objective of this study was to estimate the prevalence of CU and assess the
      burden of CU on HRQoL and healthcare resource utilization (HRU) among adults in
      Brazil. METHODS: This retrospective, cross-sectional study, pooled data from the
      2011, 2012, and 2015 National Health and Wellness Survey in Brazil (n = 36,000).
      Respondents (aged >=18 years) diagnosed with and treated for CU provided data on
      demographics, health history, HRQoL (mental and physical health status) on Short
      Form SF-36v2, presence of psychological complaints, work impairment, activity
      impairment, and HRU. Generalized linear models, controlling for covariates,
      examined differences between those treated for CU and matched controls on the
      outcome variables. RESULTS: The prevalence of diagnosed CU was 0.41% (n = 249)
      and treated CU was 0.21% (n = 127). After adjustments, CU (currently treated for
      CU) was associated with worse mental functioning, physical functioning, and
      health utilities compared with controls (all p < 0.01). CU had over twice the
      odds of anxiety and sleep difficulties, over 1.5 times the work and activity
      impairment, twice the number of total physician visits, eight times the number of
      allergist visits, and twice the number of emergency room visits as controls (all
      p < 0.01). CONCLUSIONS: Many CU patients using prescription treatment experienced
      anxiety and sleep disturbances, poorer HRQoL, significant work and activity
      impairment, and high HRU, compared with matched general population controls.
      Findings suggest an unmet need for more effective treatment and management of CU
      in Brazil. FUNDING: Novartis Pharma AG and Genentech.

PMID- 28748406
TI  - Therapeutic Effects of Topical Tranexamic Acid in Comparison with Hydroquinone in
      Treatment of Women with Melasma.
AB  - INTRODUCTION: Few studies have focused on therapeutic as well as side effects of
      tranexamic acid (TXA) as a topical drug compared to other topical drugs in
      treating melasma. The present study aimed to assess and compare the beneficial
      therapeutic effects and also side effects of local TXA in comparison with
      hydroquinone in treating women with melasma. METHODS: This randomized double
      blinded clinical trial was performed on 60 women who suffered from melasma and
      were referred to the skin disorders clinic at the Rasoul-e-Akram hospital in
      Tehran in 2015. The patients were then randomly assigned via computerized
      randomization to two groups: group A received TXA%5 (topically twice a day for 12
      weeks in the location of the melasma) and group B (received hydroquinone 2% with
      the same treatment order). Prior to intervention and at 12 weeks after
      intervention, the intensity and extension of melasma were assessed based on the
      Melasma Area and Severity Index (MASI) scoring method. RESULTS: The mean MASI
      score in both treatment groups decreased considerably after completion of
      treatment and was not significant between the two groups. No side effects were
      detected in group A, but 10% of those in group B complained of drug-related side
      effects including erythema and skin irritation (p = 0.131). Regarding the level
      of patient satisfaction, the patients in group A had a significantly higher level
      of satisfaction level of 33.3% compared with 6.7% in group B (p = 0.015) (Fig.
      9). Multivariate linear regression modeling with the presence of age, history of
      systemic disorder, drug history, and family history of melasma demonstrated no
      difference in the mean MASI between the two groups. CONCLUSION: Topical use of
      TXA significantly reduced both melanin level and MASI score. Given its high
      efficiency and low drug side effects, this regimen results in high patient
      satisfaction compared with topical hydroquinone. IRCT code: IRCT2016040627220N2.

PMID- 28748407
TI  - Putamen Volume is Negatively Correlated with the Ability to Recognize Fearful
      Facial Expressions.
AB  - Findings of previous functional magnetic resonance imaging (MRI) and
      neuropsychological studies have suggested that specific aspects of the basal
      ganglia, particularly the putamen, are involved in the recognition of emotional
      facial expressions. However, it remains unknown whether variations in putamen
      structure reflect individual differences in the ability to recognize facial
      expressions. Thus, the present study assessed the putamen volumes and shapes of
      50 healthy Japanese adults using structural MRI scans and evaluated the ability
      of participants to recognize facial expressions associated with six basic
      emotions: anger, disgust, fear, happiness, sadness, and surprise. The volume of
      the bilateral putamen was negatively associated with the recognition of fearful
      faces, and the local shapes of both the anterior and posterior subregions of the
      bilateral putamen, which are thought to support cognitive/affective and motor
      processing, respectively, exhibited similar negative relationships with the
      recognition of fearful expressions. These results suggest that individual
      differences in putamen structure can predict the ability to recognize fearful
      facial expressions in others. Additionally, these findings indicate that
      cognitive/affective and motor processing underlie this process.

PMID- 28748408
TI  - A Simple Statistical Method for the Automatic Detection of Ripples in Human
      Intracranial EEG.
AB  - High frequency oscillations (HFOs) are a promising biomarker of epileptic tissue,
      but detection of these electrographic events remains a challenge. Automatic
      detectors show encouraging results, but they typically require optimization of
      multiple parameters, which is a barrier to good performance and broad
      applicability. We therefore propose a new automatic HFO detection algorithm,
      focusing on simplicity and ease of implementation. It requires tuning of only an
      amplitude threshold, which can be determined by an iterative process or directly
      calculated from statistics of the rectified filtered data (i.e. mean plus
      standard deviation). The iterative approach uses an estimate of the amplitude
      probability distribution of the background activity to calculate the optimum
      threshold for identification of transient high amplitude events. We tested both
      the iterative and non-iterative approaches using a dataset of visually marked
      HFOs, and we compared the performance to a commonly used detector based on the
      root-mean-square. When the threshold was optimized for individual channels via
      ROC curve, all three methods were comparable. The iterative detector achieved a
      sensitivity of 99.6%, false positive rate (FPR) of 1.1%, and false detection rate
      (FDR) of 37.3%. However, in an eight-fold cross-validation test, the iterative
      method had better sensitivity than the other two methods (80.0% compared to 64.4
      and 65.8%), with FPR and FDR of 1.3, and 49.4%, respectively. The simplicity of
      this algorithm, with only a single parameter, will enable consistent application
      of automatic detection across research centers and recording modalities, and it
      may therefore be a powerful tool for the assessment and localization of epileptic
      activity.

PMID- 28748409
TI  - Evolution of Clinical Behavior in Crohn's Disease: Factors Associated with
      Complicated Disease and Surgery.
AB  - BACKGROUND: The phenotypic expression of Crohn's disease may vary over time.
      Establishment of Crohn's disease phenotypes is important for definition of
      patient care strategies. AIMS: The aim of the study was to evaluate the long-term
      evolution of patients based on disease phenotypes and the main factors associated
      with this evolution. METHODS: Data from 179 patients were collected from a
      unicentric prospective database. Montreal classification was employed. Kaplan
      Meier method was used to estimate the cumulative probability of complication
      development and surgery. Poisson regression for multivariate analysis was
      applied. The Local Institutional Review Board approved the research. RESULTS:
      Female: 54.2%. Mean age at diagnosis: 32.7 (+/-13.7) years. Behavior at
      presentation: inflammatory 62.0%, stricturing 24.6%, penetrating 13.4%; perianal
      disease: 31.8%; median follow-up time: 65.2 months (IQR 31.0-108.8). Behavior at
      follow-up period end: inflammatory 43.6%, stricturing 38.0%, penetrating 18.4%;
      perianal disease: 46.4%. Cumulative probability of being complication free in 5,
      10, and 20 years: 86.3, 66.4, and 52.2%, respectively. Cumulative probability of
      being surgery free in 5, 10, and 20 years: 87.3, 79.2, and 64.1%, respectively.
      L1 and L4 locations, use of immunosuppressive therapy, smoking, number of
      hospitalization/patient-year, abdominal surgery, age at diagnosis <40 years, and
      biological therapy were the factors associated with changes in phenotype or
      development of complications and perianal disease. CONCLUSION: Clinical behavior
      altered in about one-third of patients. The most frequent complication was a
      change to stricturing pattern. Disease location, current smoker,
      immunosuppressive therapy use, hospitalization, and abdominal surgery were
      factors associated with an unfavorable clinical evolution.

PMID- 28748410
TI  - Cytotoxic effect of co-expression of human hepatitis A virus 3C protease and
      bifunctional suicide protein FCU1 genes in a bicistronic vector.
AB  - Recent reports on various cancer models demonstrate a great potential of cytosine
      deaminase/5-fluorocytosine suicide system in cancer therapy. However, this
      approach has limited success and its application to patients has not reached the
      desirable clinical significance. Accordingly, the improvement of this suicide
      system is an actively developing trend in gene therapy. The purpose of this study
      was to explore the cytotoxic effect observed after co-expression of hepatitis A
      virus 3C protease (3C) and yeast cytosine deaminase/uracil
      phosphoribosyltransferase fusion protein (FCU1) in a bicistronic vector. A set of
      mono- and bicistronic plasmid constructs was generated to provide individual or
      combined expression of 3C and FCU1. The constructs were introduced into HEK293
      and HeLa cells, and target protein synthesis as well as the effect of 5
      fluorocytosine on cell death and the time course of the cytotoxic effect was
      studied. The obtained vectors provide for the synthesis of target proteins in
      human cells. The expression of the genes in a bicistronic construct provide for
      the cytotoxic effect comparable to that observed after the expression of genes in
      monocistronic constructs. At the same time, co-expression of FCU1 and 3C
      recapitulated their cytotoxic effects. The combined effect of the killer and
      suicide genes was studied for the first time on human cells in vitro. The
      integration of different gene therapy systems inducing cell death (FCU1 and 3C
      genes) in a bicistronic construct allowed us to demonstrate that it does not
      interfere with the cytotoxic effect of each of them. A combination of cytotoxic
      genes in multicistronic vectors can be used to develop pluripotent gene therapy
      agents.

PMID- 28748411
TI  - The role of von Willebrand factor in thrombotic microangiopathy.
AB  - Thrombotic microangiopathy (TMA) is caused by thrombus formation in the
      microvasculature. The disease spectrum of TMA includes, amongst others,
      thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic
      syndrome (aHUS). TTP is caused by defective cleavage of von Willebrand factor
      (VWF), whereas aHUS is caused by overshooting complement activation and
      subsequent endothelial cell (EC) injury. Despite their distinct pathophysiology,
      the clinical manifestation of TTP and aHUS consisting of microangiopathic
      haemolytic anaemia and thrombocytopenia is often similar and difficult to
      distinguish. Recent evidence hints at both a genetic and functional link between
      TTP and aHUS, especially between VWF and the complement system. There is novel in
      vitro evidence that complement activation not only results in VWF release from
      ECs, but that VWF also functions as a negative complement regulator, thus
      protecting the EC surface from ongoing complement attack. Although contrary to
      previous experimental work suggesting that complement can be activated on VWF
      multimers, there may be an explanation in vivo that rationalizes these apparently
      contradictory findings, whereby a system primarily meant to regulate becomes
      overwhelmed or pathologic in the disease state. The importance of unravelling
      these recent findings for our understanding of TMA pathology becomes even more
      evident considering that glomerular ECs express VWF in a heterogeneous pattern
      with an overall decreased expression level, thus potentially leaving the
      glomerular ECs vulnerable to complement-mediated injury. Taken together, these
      findings support the concept that TTP and aHUS represent two extreme ends of a
      TMA disease spectrum rather than isolated disease entities.

PMID- 28748412
TI  - Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib
      400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers.
AB  - BACKGROUND: COX-2 inhibitors can be effective for acute migraine, but none is
      supplied in a rapidly absorbed, ready-to-use oral liquid formulation. DFN-15, a
      novel oral liquid formulation of celecoxib, is being developed for the acute
      treatment of migraine with or without aura. Clinical studies with this
      formulation are ongoing. OBJECTIVES: The objectives of the present study were to
      compare the bioavailability of DFN-15 with that of the commercial formulation of
      celecoxib 400-mg oral capsules (Celebrex(r)) and to determine the dose
      proportionality of DFN-15 in healthy fasted volunteers. METHODS: This single-dose
      randomized crossover study in 16 healthy fasted volunteers evaluated the
      pharmacokinetics and relative bioavailability of DFN-15 at doses of 120, 180, and
      240 mg against the commercial formulation of celecoxib 400-mg oral capsules and
      determined the dose proportionality of DFN-15. RESULTS: The maximum observed
      plasma concentrations (C max) of celecoxib after the administration of DFN-15
      120, 180, and 240 mg (1062-1933 ng/ml) were higher than for the 400-mg oral
      capsules (611 ng/ml). The median time to peak concentration (T max) was within 1
      h for DFN-15 and 2.5 h for the oral capsules. The pharmacokinetics of DFN-15 were
      dose proportional from 120 to 240 mg. Partial area under the plasma concentration
      time curves (AUCs) from 15 min to 2 h for DFN-15 120 mg were at least threefold
      higher than for the oral capsules, and the relative bioavailability of DFN-15 was
      approximately 140% that of the oral capsules. DFN-15 was well tolerated, with no
      new or unexpected adverse events. CONCLUSIONS: Based on a faster rate of
      absorption and increased bioavailability, DFN-15 is being evaluated as an
      abortive medication for acute treatment in patients with migraine.

PMID- 28748413
TI  - Fever as a first manifestation of acute aortic dissection.

PMID- 28748415
TI  - Role of plasma-derived fibrin on keratinocyte and fibroblast wound healing.
AB  - Fibrin has excellent biocompatibility and biological properties to support tissue
      regeneration and promote wound healing. However, the role of diluted fibrin in
      wound healing has yet to be elucidated as it is commonly used in high
      concentration. This study was aimed to examine the effects of diluted plasma
      derived fibrin (PDF) on keratinocyte and fibroblast wound healing in term of cell
      proliferation, migration, extracellular matrix (ECM) production and soluble
      factor secretion. Two PDF concentrations, 10 and 20% (v/v) were tested on
      keratinocytes and fibroblasts indirectly co-cultured in the transwell system. The
      control group was cultured with 5% FBS. Results showed that PDF reduced the
      keratinocyte growth rate and fibroblast migration, and increased the fibroblast
      ECM gene expression whereby significant differences were found between the 20%
      PDF group and the 5% FBS group. Similar trend was seen for the 10% PDF group but
      the differences were not significant. Comparison of the soluble factors between
      the PDF groups demonstrated that the level of growth-related oncogene alpha,
      interleukin-8 and epithelial neutrophil-activating peptide-78 were significantly
      higher in the 10% PDF group, whilst interleukin-1 alpha and granulocyte
      macrophage colony stimulating factor were significantly more concentrated in the
      20% PDF group. Our results suggested that PDF selectively elevated the expression
      of collagen type 1 and collagen type 3 in fibroblasts but slowed down the
      migration in concentration-dependent manner. These novel findings provide new
      insight into the role of PDF in wound healing and may have important implications
      for the use of fibrin in skin tissue engineering.

PMID- 28748414
TI  - The Effect of Arterial Curvature on Blood Flow in Arterio-Venous Fistulae:
      Realistic Geometries and Pulsatile Flow.
AB  - Arterio-Venous Fistulae (AVF) are regarded as the "gold standard" method of
      vascular access for patients with End-Stage Renal Disease (ESRD) who require
      haemodialysis. However, up to 60% of AVF do not mature, and hence fail, as a
      result of Intimal Hyperplasia (IH). Unphysiological flow and oxygen transport
      patterns, associated with the unnatural and often complex geometries of AVF, are
      believed to be implicated in the development of IH. Previous studies have
      investigated the effect of arterial curvature on blood flow in AVF using
      idealized planar AVF configurations and non-pulsatile inflow conditions. The
      present study takes an important step forwards by extending this work to more
      realistic non-planar brachiocephalic AVF configurations with pulsatile inflow
      conditions. Results show that forming an AVF by connecting a vein onto the outer
      curvature of an arterial bend does not, necessarily, suppress unsteady flow in
      the artery. This finding is converse to results from a previous more idealized
      study. However, results also show that forming an AVF by connecting a vein onto
      the inner curvature of an arterial bend can suppress exposure to regions of low
      wall shear stress and hypoxia in the artery. This finding is in agreement with
      results from a previous more idealized study. Finally, results show that forming
      an AVF by connecting a vein onto the inner curvature of an arterial bend can
      significantly reduce exposure to high WSS in the vein. The results are important,
      as they demonstrate that in realistic scenarios arterial curvature can be
      leveraged to reduce exposure to excessively low/high levels of WSS and regions of
      hypoxia in AVF. This may in turn reduce rates of IH and hence AVF failure.

PMID- 28748416
TI  - Cryoprotective effect of resveratrol on DNA damage and crucial human sperm
      messenger RNAs, possibly through 5' AMP-activated protein kinase activation.
AB  - This work aimed at investigating the effect of resveratrol on (1) DNA integrity
      and (2) fertilizing capacity of sperm by quantifying the presence of key paternal
      transcripts considered as markers for male fertility (protamine 1 [PRM1] and
      protamine 2 [PRM2]) and pregnancy success (adducin 1 alpha [ADD1]) in
      cryopreserved human spermatozoa through modulation of AMP-activated protein
      kinase (AMPK). The study populations was drawn from 22 normozoospermic healthy
      volunteers which were incubated with or without AMPK activator (resveratrol
      [RSV], 15 uM) or inhibitor (Compound C [CC], 30 uM) for 1 h and were then
      cryopreserved. Untreated frozen-thawed spermatozoa served as controls. The RSV
      induced AMPK activation decreased the level of DNA fragmentation in comparison
      with the control (21.18 +/- 0.92 vs. 22.50 +/- 0.40; p < 0.01). The relative mRNA
      expression levels of protamines (1 and 2) and ADD1 in RSV pretreated frozen
      thawed human spermatozoa were also improved significantly compared to the control
      (p < 0.05). Conversely, the inhibitory effect of CC on AMPK activity deteriorated
      the deleterious effects of cryopreservation on these parameters (p < 0.01). In
      conclusion, these results demonstrated the cryoprotective effect of the RSV
      induced increase in AMPK activity on DNA integrity and key paternal transcripts
      of cryopreserved human spermatozoa. These findings are of great importance for
      improving the available cryopreservation protocols in terms of the number of
      lesions that produced over key genes and the dramatic effects on sperm DNA
      fragmentation.

PMID- 28748417
TI  - Detection of hepatitis B virus in bone allografts from donors with occult
      hepatitis B infection.
AB  - The implementation of nucleic acid testing in donor screening has improved the
      safety of tissue allografts. Although infectious disease transmission can be
      considered a rare event, the detection of occult hepatitis B infection remains
      challenging. The studies concerning this risk are mainly based on testing blood
      specimens. This work shows the correlation between results of samples obtained
      from donor blood and the corresponding tissue washing solution. Hepatitis B virus
      deoxyribonucleic acid was detected both in bone allografts from donors with
      serological profiles associated to active hepatitis B infection and occult
      hepatitis B infection. These results suggest that hepatitis B virus seems to
      concentrate in bone marrow even when a low viral load is present in peripheral
      blood. Even detection at molecular level is not enough to avoid the risk of
      hepatitis B virus transmission and a multiparametrical evaluation is required in
      tissue donor screening. The role of clinicians in recognition and reporting of
      allograft-associated infections is a major concern for the acquisition of
      experience to be applied in risk control of disease transmission.

PMID- 28748418
TI  - Left ventricular function in patients with hypertrophic cardiomyopathy and its
      relation to myocardial fibrosis and exercise tolerance.
AB  - We sought to determine the relation between myocardial extracellular volume
      (ECV), left ventricular (LV) diastolic function, and exercise tolerance in
      patients with hypertrophic cardiomyopathy (HCM). Forty five HCM patients with an
      ejection fraction >50% and no previous septal reduction therapy underwent imaging
      by CMR and transthoracic echocardiography. CMR was used to quantify LV volumes,
      mass, EF, LA volumes, scar burden, pre and post contrast T1 relaxation times and
      ECV. Echocardiography was used to measure outflow tract gradients, mitral inflow
      and annular velocities, circumferential strain, systolic, early and late
      diastolic strain rates. Exercise duration and peak oxygen consumption were noted.
      HCM patients had increased native T1 relaxation time and ECV vs. controls [ECV
      controls: 24.7 (23.2-26.4) vs. HCM: 26.8 (24.6-31.3)%, P = 0.014]. Both
      parameters were significantly associated with LV diastolic dysfunction,
      circumferential strain, diastolic strain rate and peak oxygen consumption (r = 
      0.73, P < 0.001). Compared to controls, HCM patients have significantly longer
      native T1 relaxation time and higher ECV. These structural changes lead to worse
      LV global and segmental diastolic function and in turn reduced exercise
      tolerance.

PMID- 28748419
TI  - Can We Train Military Surgeons in a Civilian Trauma Center?
AB  - INTRODUCTION: The objective of this study was to review the trauma workload and
      operative exposure in a major South African trauma center and provide a
      comparison with contemporary experience from major military conflict. MATERIALS
      AND METHODS: All patients admitted to the PMTS following trauma were identified
      from the HEMR. Basic demographic data including mechanism of injury and body
      region injured were reviewed. All operative procedures were categorized. The
      total operative volume was compared with those available from contemporary
      literature documenting experience from military conflict in Afghanistan.
      Operative volume was converted to number of cases per year for comparison.
      RESULTS: During the 4-year study period, 11,548 patients were admitted to our
      trauma center. Eighty-four percent were male and the mean age was 29 years. There
      were 4974 cases of penetrating trauma, of which 3820 (77%) were stab wounds
      (SWs), 1006 (20%) gunshot wounds (GSWs) and the remaining 148 (3%) were animal
      injuries. There were 6574 cases of blunt trauma. The mechanism of injuries was as
      follows: assaults 2956, road traffic accidents 2674, falls 664, hangings 67,
      animal injuries 42, sports injury 29 and other injuries 142. A total of 4207
      operations were performed. The volumes per year were equivalent to those reported
      from the military surgical literature. CONCLUSION: South Africa has sufficient
      burden of trauma to train combat surgeons. Each index case as identified from the
      military surgery literature has a sufficient volume in our center. Based on our
      work load, a 6-month rotation should be sufficient to provide exposure to almost
      all the major traumatic conditions likely to be encountered on the modern
      battlefield.

PMID- 28748420
TI  - Risk Factors for Early Postoperative Small Bowel Obstruction After Anterior
      Resection for Rectal Cancer.
AB  - PURPOSE: The aim of the study was to evaluate risk factors for small bowel
      obstruction (SBO) in early postoperative period after anterior resection for
      rectal cancer. METHODS: Patients who underwent anterior resection (AR) [high AR
      (HAR) or low AR (LAR)] for rectal cancer between January 2009 and April 2016 were
      enrolled into the study after fulfilling selection criteria. In included
      patients, risk factors for early postoperative SBO (EPSBO) were analyzed by means
      of univariate and multivariate analysis. Cases with perioperative major
      complications other than intestinal obstruction and with simultaneous resection
      of other organs were excluded. The same analyses were also performed for cases of
      redo surgery due to EPSBO. EPSBO was defined as clinically and radiologically
      confirmed SBO that developed after resuming oral intake within 30 days following
      surgery. The logistic regression method was used for statistical analyses.
      RESULTS: In enrolled 180 patients, EPSBO occurred in 23 (12.8%). In univariate
      analysis, male sex [odds ratio (OR) = 2.17, 95% CI = 0.82-6.84, p < 0.0001],
      previous abdominal surgery (OR = 0.20, 95% CI = 0.03-0.73, p = 0.0117), low tumor
      (OR = 3.26, 95% CI = 1.28-8.13, p = 0.0140), LAR (OR = 17.25, 95% CI = 3.49
      312.55, p < 0.0001), D3 node dissection (OR = 13.61, 95% CI = 2.75-246.69, p =
      0.0002), defunctioning ileostomy (DI) formation (OR = 9.88, 95% = 3.80-29.14, p <
      0.0001), and prolonged operation time (OR = 1.01, 95% CI = 1.00-1.01, p = 0.0122)
      were significantly related to EPSBO. Multivariate analysis demonstrated that D3
      node dissection (OR = 10.93, 95% CI = 1.94-208.23, p = 0.0038) and DI formation
      (OR = 5.82, 95% CI = 1.55-25.31, p = 0.0083) were independent risk factors for
      EPSBO. Four cases (17.4%) with EPSBO required re-operation because conservative
      therapies failed; all were laparoscopic DI formation cases. In three of those
      four cases, stenosis of stoma at the level of the posterior sheath of rectus
      abdominis muscle was the reason of SBO, and in one case it was kinking of the
      stomal limb. CONCLUSIONS: D3 lymph node dissection and DI formation are
      independent risk factors for EPSBO in AR.

PMID- 28748421
TI  - Intracorporeal Traction of the Rectum with a Beaded Plastic Urinary Drainage Bag
      Hanger: Comparison with Conventional Laparoscopic Rectal Cancer Surgery.
AB  - BACKGROUND: Laparoscopic rectal cancer surgery with proper total mesorectal
      excision is a challenge for colorectal surgeons during trouble shooting. We used
      a beaded plastic urinary drainage bag hanger to encircle the rectum and clamp
      laparoscopic rectal transaction in this study. METHODS: Sixty-three patients with
      rectal cancer underwent laparoscopic radical rectal resection with curative
      intent between February 2015 and December 2015. Plastic beaded form urinary Foley
      catheter bag hanger was inserted intracorporeally via right lower 12-mm trocar,
      encircling the rectal tube distal to the rectal lesion followed by fastening.
      Thirty patients in the rectal resection group (28 laparoscopic, 2 robotic
      assisted) using the commercial beaded plastic hanger for Foley catheter drainage
      were compared to 33 patients who underwent conventional laparoscopic rectal
      resection. RESULTS: Low anterior resection was performed for both groups. The
      Foley bag hanger group had less operation time (162.6 min vs. 187.3 min, p =
      0.006) and fewer numbers of stapler cartilage (1.6 vs. 2.1, p = 0.001).
      CONCLUSIONS: Intracorporeal ligation of the rectum with a beaded plastic Foley
      catheter bag hanger could be used as a valuable method for rectal handling and
      transaction in laparoscopic rectal cancer surgery.

PMID- 28748422
TI  - Safety and Feasibility of Umbilical Diverting Loop Ileostomy for Patients with
      Rectal Tumor.
AB  - BACKGROUND: Fashioning an ileostomy in the umbilicus and combining the trauma
      from extraction of colorectum with that from ileostomy should be less invasive
      and lead to improved cosmetic outcomes. However, there are only a few reports
      regarding umbilical ileostomy. METHODS: We retrospectively collected data for 121
      consecutive patients with rectal tumor who underwent elective laparoscopic rectal
      resection with diverting loop ileostomy between 2010 and 2015 at Osaka University
      Hospital, Japan. The safety and feasibility of umbilical diverting loop ileostomy
      and its influence on stoma care were investigated. RESULTS: A total of 83
      patients were included in this study; of these, 30 underwent umbilical diverting
      loop ileostomy and 53 underwent conventional diverting loop ileostomy, which was
      created in the right lower quadrant of the abdomen. The umbilical and
      conventional groups showed similar rates of postoperative and stoma-related
      complications (26.7 vs. 32.1%, p = 0.804 and 3.3 vs. 3.8%, p = 1.000,
      respectively). Level of parastomal dermatitis was evaluated by DET score at three
      time points (stoma self-management establishment, first outpatient review post
      discharge, and just before stoma closure). DET scores at any time points did not
      differ significantly between the two groups. CONCLUSIONS: Umbilical diverting
      loop ileostomy is comparable to conventional ileostomy with regard to safety and
      feasibility. Our methods for umbilical ileostomy using the umbilical skin flap
      were less invasive and did not have a negative impact on stoma care and
      parastomal dermatitis. Umbilical ileostomy may be a promising alternative to
      conventional ileostomy in selected cases.

PMID- 28748423
TI  - Impact of interstitial lung disease on mortality of patients with rheumatoid
      arthritis.
AB  - To identify the prevalence of interstitial lung disease (ILD) in Korean patients
      with rheumatoid arthritis (RA) and assess its effect on mortality. A total of
      3555 patients with RA, with chest X-ray or chest computed tomography (CT) data at
      enrollment were extracted from the KORean Observational study Network for
      Arthritis cohort, a nationwide prospective cohort for patients with RA in Korea.
      The patients were classified into two groups: (1) an ILD group by chest X-ray or
      chest CT scan, and (2) a non-ILD group by these modalities. After comparing the
      characteristics of the groups at enrollment, mortalities were compared using the
      log-rank test. To explore the impact of ILD on mortality, Cox proportional hazard
      models were used. Sixty-four patients (1.8%) were identified with ILD. Male and
      older patients were more common in the ILD group. During a mean follow-up of 24
      months, 6 patients (9.4%) in the ILD group and 25 patients (0.7%) in the non-ILD
      group died; the survival rate was significantly worse in the ILD group (p <
      0.01). On adjusted analysis, ILD was significantly associated with increased
      mortality (HR 7.89, CI 3.16-19.69, p < 0.01); the risk of death in patients with
      ILD was even higher than in patients with cardiovascular disease (CVD, HR 4.10,
      CI 1.79-9.37, p < 0.01). The prevalence of ILD was 1.8% in Korean patients with
      RA. ILD is a major risk factor for mortality in patients with RA.

PMID- 28748424
TI  - Association of ADAM 12 polymorphisms with the risk of knee osteoarthritis: meta
      analysis of 5048 cases and 6848 controls.
AB  - Several studies have suggested the association between ADAM 12 polymorphisms and
      the risk of osteoarthritis (OA), but the results remained controversial.
      Therefore, we designed a meta-analysis to systematically evaluate the association
      on this issue. A literature search for eligible studies was conducted in PubMed,
      Web of Science and Google Scholar databases. The association between ADAM 12
      polymorphisms and knee OA risk was calculated by odds ratios (ORs) and 95%
      confidence intervals (CIs). Study heterogeneity, sensitivity and publication bias
      analyses were also conducted. Ten articles covering 5048 cases and 6848 controls
      met our criteria for the final analysis. We found that the rs1871054 was
      significantly associated with the risk of knee OA (allele model OR 1.72, 95% CI
      1.43-2.07, P < 0.001; additive model: OR 2.06, 95% CI 1.19-3.56, P = 0.010;
      dominant model: OR 2.45, 95% CI 1.85-3.25, P < 0.001; recessive model: OR 1.54,
      95% CI 1.13-2.10, P = 0.007). rs1044122 was significantly associated with knee OA
      susceptibility in recessive model (OR 1.45, 95% CI 1.03-2.04, P = 0.031). For
      rs3740199 and rs1278279, no significant associations with knee OA were found. In
      the stratified analysis by gender, significant association was identified with
      the risk of knee OA for rs3740199 in men in allele model (OR 2.41, 95% CI 1.51
      3.84, P < 0.001), dominant model (OR 2.68, 95% CI 1.17-6.14, P = 0.02) and
      recessive model (OR 3.51, 95% CI 1.68-7.36, P = 0.001), but not for additive
      model (OR 1.30, 95% CI 0.81-2.08, P = 0.28). This meta-analysis suggests that the
      ADAM 12 genetic polymorphisms rs1871054 and rs1044122 might be associated with
      risk of knee OA; rs3740199 might be associated with risk of knee OA in men.
      Further well-designed and large scale studies are warranted to validate these
      associations.

PMID- 28748425
TI  - Hydroxychloroquine dosing in immune-mediated diseases: implications for patient
      safety.
AB  - Evidence suggests that hydroxychloroquine (HCQ) retinal toxicity is more common
      than previously thought. Adhering to careful weight-based dosing can
      significantly reduce the risk of this adverse event and is recommended in recent
      guidelines. We used electronic health record data from a large health system to
      examine HCQ dosing over a 5-year period and identify risk factors associated with
      higher dosage of HCQ. We constructed a longitudinal, retrospective cohort of
      patients with HCQ prescriptions (1681 patients with 3490 prescribing events)
      between 2012 and 2016. We measured HCQ dosing patterns relative to guidelines
      (<6.5 and <5.0 mg/kg) over time and used longitudinal multivariate mixed effects
      logistic regression to identify sociodemographic, clinical and health system
      factors associated with receiving higher than recommended doses of HCQ. The
      proportion of patients receiving doses above 6.5 mg/kg decreased from 12% in 2012
      to 7% by 2016. Similarly, the proportion of patients with doses above 5.0 mg/kg
      fell from 38% in 2012 to 30% in 2016. Low body weight (<68 kg) was strongly
      associated with receiving doses of HCQ above 6.5 mg/kg across all time points,
      even after adjusting for other factors (odds ratios ranging from 13.2 to 21.0).
      Although the proportion of patients receiving higher than recommended HCQ doses
      has declined over a period of 5 years, a substantial number of individuals remain
      at increased risk for toxicity. Given the widespread use of HCQ in immune
      mediated diseases, our study suggests that interventions aimed to ensure
      appropriate dosing are warranted to improve patient safety.

PMID- 28748426
TI  - Quality of care in gout: a clinical audit on treating to the target with urate
      lowering therapy in real-world gout patients.
AB  - The current paper aimed to describe the quality of care for gout patients by
      showing the clinical outcomes achieved in two patient cohorts in which differing
      targeted urate lowering therapy (ULT) treatment approaches were employed, both
      aiming to reach the European League Against Rheumatism recommended serum urate
      (sUA) targets. A retrospective medical chart review study was conducted. Data
      from the medical records of gout patients from two clinical centers in The
      Netherlands, both applying targeted ULT treatments (albeit using different
      approaches), were reviewed. Patients in cohort A were given a combination of
      xanthine oxidase inhibitors with uricosurics if treatment with allopurinol
      monotherapy failed to reach sUA target levels, whereas patients in cohort B were
      treated with sequential monotherapy. Data on patient characteristics and clinical
      outcomes were collected. A total of 177 patient dossiers were included: 99 from
      cohort A and 78 from cohort B. The great majority (n = 146, 82.5%) of the
      patients in both cohorts had a current sUA level <360 umol/L. In addition, more
      than half (n = 104, 58.8%) of the patients met the stringent sUA target level of
      <300 umol/L. The largest reductions in mean sUA levels were observed for patients
      who were treated with combination therapy. This clinical audit of two cohorts of
      gout patients provides initial-yet promising-results regarding the proportion of
      real-world gout patients in whom recommended that sUA target levels can be
      achieved, and demonstrates the added value that a targeted treatment approach may
      have in reaching these goals.

PMID- 28748427
TI  - Measurements of stem diameter: implications for individual- and stand-level
      errors.
AB  - Stem diameter is one of the most common measurements made to assess the growth of
      woody vegetation, and the commercial and environmental benefits that it provides
      (e.g. wood or biomass products, carbon sequestration, landscape remediation). Yet
      inconsistency in its measurement is a continuing source of error in estimates of
      stand-scale measures such as basal area, biomass, and volume. Here we assessed
      errors in stem diameter measurement through repeated measurements of individual
      trees and shrubs of varying size and form (i.e. single- and multi-stemmed) across
      a range of contrasting stands, from complex mixed-species plantings to commercial
      single-species plantations. We compared a standard diameter tape with a Stepped
      Diameter Gauge (SDG) for time efficiency and measurement error. Measurement
      errors in diameter were slightly (but significantly) influenced by size and form
      of the tree or shrub, and stem height at which the measurement was made. Compared
      to standard tape measurement, the mean systematic error with SDG measurement was
      only -0.17 cm, but varied between -0.10 and -0.52 cm. Similarly, random error was
      relatively large, with standard deviations (and percentage coefficients of
      variation) averaging only 0.36 cm (and 3.8%), but varying between 0.14 and 0.61
      cm (and 1.9 and 7.1%). However, at the stand scale, sampling errors (i.e. how
      well individual trees or shrubs selected for measurement of diameter represented
      the true stand population in terms of the average and distribution of diameter)
      generally had at least a tenfold greater influence on random errors in basal area
      estimates than errors in diameter measurements. This supports the use of diameter
      measurement tools that have high efficiency, such as the SDG. Use of the SDG
      almost halved the time required for measurements compared to the diameter tape.
      Based on these findings, recommendations include the following: (i) use of a tape
      to maximise accuracy when developing allometric models, or when monitoring
      relatively small changes in permanent sample plots (e.g. National Forest
      Inventories), noting that care is required in irregular-shaped, large-single
      stemmed individuals, and (ii) use of a SDG to maximise efficiency when using
      inventory methods to assess basal area, and hence biomass or wood volume, at the
      stand scale (i.e. in studies of impacts of management or site quality) where
      there are budgetary constraints, noting the importance of sufficient sample sizes
      to ensure that the population sampled represents the true population.

PMID- 28748428
TI  - Land use and land cover (LULC) of the Republic of the Maldives: first national
      map and LULC change analysis using remote-sensing data.
AB  - The Maldives islands in recent decades have experienced dramatic land-use change.
      Uninhabited islands were turned into new resort islands; evergreen tropical
      forests were cut, to be replaced by fields and new built-up areas. All these
      changes happened without a proper monitoring and urban planning strategy from the
      Maldivian government due to the lack of national land-use and land-cover (LULC)
      data. This study aimed to realize the first land-use map of the entire Maldives
      archipelago and to detect land-use and land-cover change (LULCC) using high
      resolution satellite images and socioeconomic data. Due to the peculiar
      geographic and environmental features of the archipelago, the land-use map was
      obtained by visual interpretation and manual digitization of land-use patches.
      The images used, dated 2011, were obtained from Digital Globe's WorldView 1 and
      WorldView 2 satellites. Nine land-use classes and 18 subclasses were identified
      and mapped. During a field survey, ground control points were collected to test
      the geographic and thematic accuracy of the land-use map. The final product's
      overall accuracy was 85%. Once the accuracy of the map had been checked, LULCC
      maps were created using images from the early 2000s derived from Google Earth
      historical imagery. Post-classification comparison of the classified maps showed
      that growth of built-up and agricultural areas resulted in decreases in forest
      land and shrubland. The LULCC maps also revealed an increase in land reclamation
      inside lagoons near inhabited islands, resulting in environmental impacts on
      fragile reef habitat. The LULC map of the Republic of the Maldives produced in
      this study can be used by government authorities to make sustainable land-use
      planning decisions and to provide better management of land use and land cover.

PMID- 28748429
TI  - Admission Control Policies for Surgery Patients.
AB  - In China, day surgery has been promoted because its operation time and post
      operative hospital stay are shorter than those of elective surgery. Day surgery
      can speed up the turnover of beds and operation rooms. Usually, the conditions of
      elective surgery patients are more complicated than those of day surgery
      patients. The development of the discipline, which means that the hospital has
      improved the skills of the doctors and the ability of doctors to cope with
      serious diseases and has increased the overall medical level of the hospital,
      requires surgeons to operate in some complicated elective surgeries. In the case
      of operating rooms and beds in short supply, there is a trade-off between the
      promotion of day surgery and the development of the discipline. Day surgery is
      relatively uncomplicated, but it requires more highly qualified surgeons.
      However, the development of the discipline requires surgeons to take on some
      complicated elective surgeris. Moreover, according to the notion of grading
      treatment, class-A tertiary hospitals are more suitable for patients with
      relatively complicated and serious conditions. In the emerging context of day
      surgery, highly qualified surgeons need to perform both day surgeries and
      elective surgeries. This paper studied how to control the admission of surgery
      patients. We take into account both day surgery promotion and discipline
      development in decision-making. A dynamic programming model was built for
      admission control, and a gamma-adjust-threshold heuristic policy was proposed. We
      then compared the heuristic policy to three other policies through simulation.
      The results show that our heuristic policy outperforms the hospital's target
      policy.

PMID- 28748430
TI  - iNICU - Integrated Neonatal Care Unit: Capturing Neonatal Journey in an
      Intelligent Data Way.
AB  - Neonatal period represents first 28 days of life, which is the most vulnerable
      time for a child's survival especially for the preterm babies. High neonatal
      mortality is a prominent and persistent problem across the globe. Non
      availability of trained staff and infrastructure are the major recognized hurdles
      in the quality care of these neonates. Hourly progress growth charts and reports
      are still maintained manually by nurses along with continuous calculation of drug
      dosage and nutrition as per the changing weight of the baby. iNICU (integrated
      Neonatology Intensive Care Unit) leverages Beaglebone and Intel Edison based IoT
      integration with biomedical devices in NICU i.e. monitor, ventilator and blood
      gas machine. iNICU is hosted on IBM Softlayer based cloud computing
      infrastructure and map NICU workflow in Java based responsive web application to
      provide translational research informatics support to the clinicians. iNICU
      captures real time vital parameters i.e. respiration rate, heart rate, lab data
      and PACS amounting for millions of data points per day per child. Stream of data
      is sent to Apache Kafka layer which stores the same in Apache Cassandra NoSQL.
      iNICU also captures clinical data like feed intake, urine output, and daily
      assessment of child in PostgreSQL database. It acts as first Big Data hub (of
      both structured and unstructured data) of neonates across India offering temporal
      (longitudinal) data of their stay in NICU and allow clinicians in evaluating
      efficacy of their interventions. iNICU leverages drools based clinical rule based
      engine and deep learning based big data analytical model coded in R and PMML.
      iNICU solution aims to improve care time, fills skill gap, enable remote
      monitoring of neonates in rural regions, assists in identifying the early onset
      of disease, and reduction in neonatal mortality.

PMID- 28748431
TI  - Erratum to: Is 1,25-Dihydroxyvitamin D3 Receptor Expression a Potential Achilles'
      Heel of CD44+ Oral Squamous Cell Carcinoma Cells?

PMID- 28748432
TI  - Resin glycosides from Convolvulaceae plants.
AB  - Resin glycosides are well known as purgative ingredients, which are
      characteristic of certain crude drugs such as Mexican Scammony Radix, Orizabae
      Tuber, and Jalapae Tuber, all of which originate from Convolvulaceae plants.
      Depending on their solubility in ether, these are roughly classified into two
      groups-jalapin (soluble) and convolvulin (insoluble). Almost all jalapins
      hitherto isolated and characterized had common intramolecular macrocyclic ester
      structures. These are composed of 1 mol of oligoglycoside of hydroxyl fatty acid
      (glycosidic acid) partially acylated by some organic acids at the sugar moiety,
      some examples of which are ester-type dimers. On the other hand, convolvulin is
      regarded as an oligomer of a variety of acylated glycosidic acids. This review
      describes the isolation and structural elucidation of resin glycosides from some
      Convolvulaceae plants, including Ipomoea operculata, Pharbitis nil, Quamoclit
      pennata, Calystegia soldanella, and I. muricata.

PMID- 28748433
TI  - A supplement to Prof. Shoji Shibata's achievements: the history of "Shoso-in
      Medicines" and the reason why Magnolia obovata (old name: Hoogashiwa) was not
      given a Chinese herbal name in Japan's oldest anthology "Man'yoshu".
AB  - Prof. Shoji Shibata (1916-2016) left behind remarkable achievements in the field
      of the history of pharmacy. Among those, the scientific survey on medicines
      preserved in Shoso-in, globally known as the World Cultural Heritage, is of
      particular interest, drawing wide attention from scholars to the general public.
      Its most spectacular and also shocking study in the field of pharmacognosy will
      be the one on the true origin of Koboku (Houpu) that seems quite ordinary from
      its name. Prof. Shibata revealed that it is of juglandaceous origin that is
      completely different from what is known today under the same name. Juglandaceous
      Koboku, which came into wide use in China at that time, was neither a homonym nor
      adulteration according to the pertinent description on this medicine in Chinese
      herbal books, and, furthermore, was regarded as authentic even at the Song
      Dynasty. In the Nara period of Japan, the name of Koboku is not found except for
      the archives preserved in Shoso-in, while the name of Hoogashiwa, an old name of
      Hoonoki (Magnolia obovata), appears only in "Man'yoshu", Japan's oldest
      anthology. Therefore, Hoonoki was not recognized as Koboku at that time.
      Interestingly, this fact is also reflected in "Man'yoshu". In the epigraph of two
      poems including Hoonoki, the Japanese name is used instead of the Chinese name
      that should be employed in principle. The historical circumstances of "Shoso-in
      Medicines" will also be outlined with elaborate and reliable evidence.

PMID- 28748434
TI  - Erratum to: Portuguese agriculture and the evolution of greenhouse gas emissions
      can vegetables control livestock emissions?

PMID- 28748435
TI  - Effects of salinity on oil dispersant toxicity in the eastern mud snail,
      Ilyanassa obsoleta.
AB  - Chemical dispersants can be a beneficial method for breaking up oil slicks;
      however, their use in mitigation could pose potential toxic effects on the marine
      ecosystem. Dispersants may be transported to lower salinity habitats, where
      toxicity data for aquatic species have not been established. This study examined
      the effect of salinity on oil dispersant toxicity in the eastern mud snail,
      Ilyanassa obsoleta, using two dispersants authorized for oil spill response,
      Corexit(r) 9500A and Finasol(r) OSR 52. Median lethal toxicity values (LC50) and
      sublethal effects were examined at 10, 20, and 30 ppt salinity in adult and
      larval mud snails. Two biomarkers (lipid peroxidation and acetylcholinesterase)
      were used to measure sublethal effects. The 96-h static renewal LC50 values
      indicated significant differences in toxicity between dispersants and salinities.
      Larval snails were significantly more sensitive than adult snails to both
      dispersants, and both life stages were significantly more sensitive to Finasol
      than to Corexit. Larval snails were more sensitive to dispersants at lower
      salinity, but adult snails were more sensitive at higher salinities. Dispersants
      increased lipid peroxidation and decreased acetylcholinesterase activity. These
      results demonstrate that dispersant toxicity varies among compounds and organism
      life stages, and that physicochemical properties of the environment, such as
      salinity, can affect the potential toxicity to estuarine species.

PMID- 28748436
TI  - Organophosphorus pesticide mixture removal from environmental matrices by a soil
      Streptomyces mixed culture.
AB  - The current study aimed to evaluate the removal of a pesticide mixture composed
      of the insecticides chlorpyrifos (CP) and diazinon (DZ) from liquid medium, soil
      and a biobed biomixture by a Streptomyces mixed culture. Liquid medium
      contaminated with 100 mg L-1 CP plus DZ was inoculated with the Streptomyces
      mixed culture. Results indicated that microorganisms increased their biomass and
      that the inoculum was viable. The inoculum was able to remove the pesticide
      mixture with a removal rate of 0.036 and 0.015 h-1 and a half-life of 19 and 46 h
      1 for CP and DZ, respectively. The sterilized soil and biobed biomixture
      inoculated with the mixed culture showed that Streptomyces was able to colonize
      the substrates, exhibiting an increase in population determined by quantitative
      polymerase chain reaction (q-PCR), enzymatic activity dehydrogenase (DHA) and
      acid phosphatase (APP). In both the soil and biomixture, limited CP removal was
      observed (6-14%), while DZ exhibited a removal rate of 0.024 and 0.060 day-1 and
      a half-life of 29 and 11 days, respectively. Removal of the organophosphorus
      pesticide (OP) mixture composed of CP and DZ from different environmental
      matrices by Streptomyces spp. is reported here for the first time. The
      decontamination strategy using a Streptomyces mixed culture could represent a
      promising alternative to eliminate CP and DZ residues from liquids as well as to
      eliminate DZ from soil and biobed biomixtures.

PMID- 28748437
TI  - Application of ultrasound modified corn straw as adsorbent for malachite green
      removal from synthetic and real effluents.
AB  - This work aimed to study the removal of malachite green dye from wastewaters
      through adsorption using raw corn straw (RCS) and ultrasound-assisted modified
      corn straw (MCS). RCS and MCS were prepared and characterized in detail. The
      characterization indicated that RCS and MCS presented favorable structures for
      malachite green adsorption and that the ultrasound treatment provided a
      disorganization of the adsorbent's crystalline regions and also caused the
      formation of cavities and protuberances. The adsorption study was performed by
      equilibrium isotherms, kinetic curves, thermodynamic parameters, and application
      in real effluents composed of dye mixtures and inorganic compounds. The Elovich
      model was suitable for the adsorption kinetics and the Freundlich model was
      appropriate to represent the equilibrium. The maximum experimental adsorption
      capacities were 200 mg g-1 for RCS and 210 mg g-1 for MCS, obtained at 328 K. MCS
      was more effective than RCS to treat real effluents, attaining around 92% of
      color removal.

PMID- 28748438
TI  - Combined fast selective reduction using Mn-based catalysts and nonthermal plasma
      for NOx removal.
AB  - In this study, the concept of fast SCR for NO reduction with NH3 as reducing
      agent is realized via the combination of nonthermal plasma (NTP) with Mn-based
      catalyst. Experimental results indicate that 10% wt. Mn-Ce-Ni/TiO2 possesses
      better physical and chemical properties of surface, resulting in higher NO
      removal efficiency if compared with 10% wt. Mn-Ce/TiO2 and 10% wt. Mn-Ce-Cu/TiO2.
      Mn-Ce-Ni/TiO2 of 10% wt. achieves 100% NOx conversion at 150  degrees C, while
      10% wt. Mn-Ce/TiO2 and 10% wt. Mn-Ce-Cu/TiO2 need to be operated at a temperature
      above 200  degrees C for 100% NOx conversion. However, NO conversion achieved
      with 10% wt. Mn-Ce-Ni/TiO2 is significantly reduced as H2O(g) and SO2 are
      introduced into the SCR system simultaneously. Further, two-stage system (SCR
      with DBD) is compared with the catalyst-alone for NOx conversion and N2
      selectivity. The results indicate that 100% NOx conversion can be achieved with
      two-stage system at 100  degrees C, while N2 selectivity reaches 80%.
      Importantly, NOx conversion achieved with two-stage system could maintain >95% in
      the presence of C2H4, CO, SO2, and H2O(g), indicating that two-stage system has
      better tolerance for complicated gas composition. Overall, this study
      demonstrates that combining NTP with Mn-based catalyst is effective in reducing
      NOx emission at a low temperature (<=200  degrees C) and has good potential for
      industrial application.

PMID- 28748439
TI  - Enhanced removal of humic acid from micro-polluted source water in a surface
      discharge plasma system coupled with activated carbon.
AB  - Surface discharge plasma (SDP) combined with activated carbon (AC) was employed
      to eliminate dissolved organic matter from micro-polluted source water, with
      humic acid (HA) as the model pollutant. Synergistic effect on HA removal was
      observed in the SDP-AC system; HA removal efficiency reached 60.9% within 5-min
      treatment in the SDP-AC system with 5.0 g AC addition, whereas 16.7 and 17.4% of
      HA were removed in sole SDP system and AC adsorption, respectively. Scanning
      electron microscope and Boehm titration analysis showed that chemical reactions
      between active species and functional groups of AC occurred. The existence of
      isopropanol or benzoquinone exhibited inhibitive effects on HA removal in the SDP
      system, while these inhibitive effects were weakened in the SDP-AC system. The
      influences of AC on ozone equivalent concentration and H2O2 concentration were
      evaluated, and there were approximately 39 and 20% decline in ozone equivalent
      concentration and H2O2 concentration within 6-min treatment in the SDP-AC system,
      respectively, compared with those in the sole SDP system. Dissolved organic
      carbon, specific ultraviolet absorbance, and UV absorption ratios analysis
      demonstrated that the SDP treatment destroyed the chromophoric groups, double
      bonds, and aromatic structure of HA molecules, and these destructive actions were
      strengthened by AC.

PMID- 28748440
TI  - Pharmaceuticals released from senior residences: occurrence and risk evaluation.
AB  - One of the main pursuits, yet most difficult, in monitoring studies is to
      identify the sources of environmental pollution. In this study, we have
      identified health-care facilities from south European countries as an important
      source of pharmaceuticals in the environment. We have estimated that compounds
      consumed in by the elderly and released from effluents of senior residences can
      reach river waters at a concentration higher than 0.01 MUg/L, which is the
      European Medicines Agency (EMA) threshold for risk evaluation of pharmaceuticals
      in surface waters. This study has been based on five health institutions in
      Portugal, Spain, and France, with 52 to 130 beds. We have compiled the
      pharmaceuticals dispensed on a daily base and calculated the consumption rates.
      From 54.9 to 1801 g of pharmaceuticals are consumed daily, with laxatives,
      analgesics, antiepileptics, antibiotics, and antidiabetic agents being the main
      drug families administered. According to excretion rates, dilution in the
      sewerage system, and elimination in wastewater treatment plants, macrogol,
      metformin, paracetamol, acetylcysteine, amoxicillin, and gabapentin, among
      others, are expected to reach river waters. Finally, we discuss the risk
      management actions related to the discharge of pharmaceuticals from senior
      residences to surface waters.

PMID- 28748441
TI  - Ozone risk assessment in three oak species as affected by soil water
      availability.
AB  - To derive ozone (O3) dose-response relationships for three European oak species
      (Quercus ilex, Quercus pubescens, and Quercus robur) under a range of soil water
      availability, an experiment was carried out with 2-year-old potted seedlings
      exposed to three levels of water availability in the soil and three levels of O3
      pollution for one growing season in an ozone free-air controlled exposure (FACE)
      facility. Total biomass losses were estimated relative to a hypothetical clean
      air at the pre-industrial age, i.e., at 10 ppb as daily average (M24). A stomatal
      conductance model was parameterized with inputs from the three species for
      calculating the stomatal O3 flux. Exposure-based (M24, W126, and AOT40) and flux
      based (phytotoxic O3 dose (POD)0-3) dose-response relationships were estimated
      and critical levels (CL) were calculated for a 5% decline of total biomass.
      Results show that water availability can significantly affect O3 risk assessment.
      In fact, dose-response relationships calculated per individual species at each
      water availability level resulted in very different CLs and best metrics. In a
      simplified approach where species were aggregated on the basis of their O3
      sensitivity, the best metric was POD0.5, with a CL of 6.8 mmol m-2 for the less
      O3-sensitive species Q. ilex and Q. pubescens and of 3.5 mmol m-2 for the more O3
      sensitive species Q. robur. The performance of POD0, however, was very similar to
      that of POD0.5, and thus a CL of 6.9 mmol m-2 POD0 and 3.6 mmol m-2 POD0 for the
      less and more O3-sensitive oak species may be also recommended. These CLs can be
      applied to oak ecosystems at variable water availability in the soil. We conclude
      that PODy is able to reconcile the effects of O3 and soil water availability on
      species-specific oak productivity.

PMID- 28748442
TI  - Targeted Therapy and Local Control: The Dynamic Duo.

PMID- 28748444
TI  - Sustained Growth of a University-Based Endocrine Surgery Program Over 10 Years.
AB  - BACKGROUND: Endocrine surgery continues to mature as a subspecialty field. We
      describe the clinical performance of an academic endocrine surgery program (ESP)
      over its first 10 years. METHODS: We examined all endocrine procedures performed
      during the 10-year period (2006-2015) following the inception of the ESP.
      Institutional and state-level data on case volume, patient geographic origin, and
      hospital-side costs were obtained. RESULTS: Endocrine case volume increased by
      approximately ninefold over the study period (from 102 cases in 2006 to 919 cases
      in 2015). The rate of growth remained approximately linear, and was driven by
      geographic expansion of referral regions coupled with transitioning low- to
      moderate-acuity operations to venues outside of the main tertiary care hospital.
      Market share across the eight-county Southern California region grew by more than
      twofold over the study period. Increased utilization of outpatient surgery led to
      cost reductions, averaging 11.1% per case by 2015. CONCLUSIONS: Establishment of
      an academic ESP can lead to sustained clinical growth and a fundamental shift in
      regional referral patterns. The nation's continued need for skilled high-volume
      endocrine surgeons represents opportunities for medical centers to institute
      their own dedicated endocrine surgery programs.

PMID- 28748443
TI  - Adherence to Guidelines for Adult (Non-GIST) Soft Tissue Sarcoma in the
      Netherlands: A Plea for Dedicated Sarcoma Centers.
AB  - INTRODUCTION: Optimal management of soft tissue sarcoma (STS) remains a
      challenge. A nationwide survey assessed the quality of STS care in the
      Netherlands, thereby aiming to identify potentialities for improvement through
      more centralized disease management. METHODS: From the Netherlands Cancer
      Registry (NCR), data were obtained on 3317 adult STS patients (excluding
      gastrointestinal stromal tumor, GIST) diagnosed in 2006-2011. Logistic regression
      models were employed to compare outcomes on selected clinical indicators
      reflecting prevailing STS guidelines between high-volume (>=10 resections
      annually) and low-volume (<10 resections) hospitals, between academic and general
      hospitals, and between sarcoma research centers and other hospitals, adjusted for
      case mix. Analyses were performed on imputed datasets (m = 50), generated through
      multiple imputations by chained equations. RESULTS: Overall, 89% of patients
      underwent surgical resection. Resection status remained unknown in 24% (excluding
      those with metastasized disease), and grade was not documented for one-third of
      tumors. Microscopic residual disease was detected in 20% with an increased risk
      for older patients, larger and deeply located tumors, and those located in the
      (retro)peritoneum or upper extremity. Almost half of patients with an R1
      resection received adjuvant radiotherapy. Following adjustment for case mix
      factors, patients treated in high-volume hospitals less often had macroscopic
      residual disease (R2 resection; adjusted odds ratio: 0.54). A strongly skewed
      distribution of surgical volumes was observed. CONCLUSIONS: These survey results
      indicate a potential for improving Dutch STS care. More centralized sarcoma
      management should improve definitive pathology reporting on tumor
      characteristics, adherence to treatment guidelines and overall disease outcome.

PMID- 28748445
TI  - Surgeon and Radiation Oncologist Views on Omission of Adjuvant Radiotherapy for
      Older Women with Early-Stage Breast Cancer.
AB  - PURPOSE: Although clinical trials have shown no survival advantage and only a
      modest improvement in local control from adjuvant radiotherapy after lumpectomy
      in older women with stage I, estrogen receptor-positive (ER+) breast cancer,
      radiotherapy is commonly administered, raising concerns about overtreatment.
      Therefore, we sought to evaluate physician views on omission of radiotherapy in
      older women with favorable prognosis breast cancer. METHODS: We surveyed a
      national sample of 713 radiation oncologists and 879 surgeons. Of these, 1504
      were eligible and 825 responded (55%). We assessed responses to clinical
      scenarios, knowledge of pertinent risk information, and correlates of views on
      radiotherapy omission. RESULTS: Omission of radiotherapy in patients age >=70
      years with stage I, ER+ breast cancer, treated with lumpectomy and endocrine
      therapy, was felt to be unreasonable by 40% of surgeons and 20% of radiation
      oncologists. Many surgeons (29%) and radiation oncologists (10%) erroneously
      associated radiotherapy in older women with improvement in survival. Similarly,
      32% of surgeons and 19% of radiation oncologists tended to substantially
      overestimate the risk of locoregional recurrence in older women with omission of
      RT. In a scenario with an 81-year-old with multiple comorbidities, 31% of
      surgeons and 35% of radiation oncologists would still recommend radiotherapy.
      CONCLUSIONS: Many radiation oncologists and surgeons continue to consider
      omission of radiotherapy as substandard therapy and overestimate the benefits of
      radiotherapy. Surgeons, in addition to radiation oncologists, may have an
      opportunity to play a pivotal role in reducing overuse of aggressive care in this
      setting.

PMID- 28748446
TI  - Selenium Protects against Lead-induced Apoptosis via Endoplasmic Reticulum Stress
      in Chicken Kidneys.
AB  - Lead (Pb) is a toxic heavy metal and can harm organisms by inducing apoptosis.
      Selenium (Se), an essential trace element for humans and animals, can alleviate
      heavy metal toxicity. The aim of our study is to investigate alleviative effect
      of Se on Pb-induced apoptosis via endoplasmic reticulum (ER) stress in chicken
      kidneys. One hundred and eighty male chickens were randomly divided into four
      groups at 7 days of age and were fed with commercial diet (containing 0.49 mg/kg
      Se) and drinking water, Na2SeO3-added commercial diet (containing 1 mg/kg Se) and
      drinking water, the commercial diet and (CH3OO)2Pb-added drinking water
      (containing 350 mg/L Pb), and Na2SeO3-added commercial diet (containing 1 mg/kg
      Se) and (CH3OO)2Pb-added drinking water (containing 350 mg/L Pb), respectively.
      On the 30th, 60th, and 90th days of the experiment period, 15 chickens in each
      group were euthanized and the kidneys were collected. Following contents were
      performed: kidney ultrastructure; nitric oxide (NO) content; inducible nitric
      oxide synthase (iNOS) activity; relative messenger RNA (mRNA) and protein
      expression of iNOS, ER-related genes (glucose-regulated protein (GRP)78, GRP94,
      activating transcription factor (ATF)4, ATF6, and iron-responsive element (IRE)),
      and apoptosis-related genes (caspase-3 and B cell lymphoma-2 (Bcl-2)); and
      caspase-12 protein expression. The results indicated that Pb changed kidney
      ultrastructural structure; decreased Bcl-2 mRNA and protein expression; and
      increased NO content, iNOS activity, relative mRNA and protein expression of
      iNOS, ER-related genes, and caspase-3 and caspase-12 protein expression. Se
      attenuated above changes caused by Pb. Pb had time-dependent manners on NO
      content, GRP78, GRP94, ATF4, IRE, and caspase-3 mRNA expression. Se attenuated Pb
      induced apoptosis via ER stress in the chicken kidneys.

PMID- 28748447
TI  - Cross-modal working memory binding and L1-L2 word learning.
AB  - The ability to create temporary binding representations of information from
      different sources in working memory has recently been found to relate to the
      development of monolingual word recognition in children. The current study
      explored this possible relationship in an adult word-learning context. We
      assessed whether the relationship between cross-modal working memory binding and
      lexical development would be observed in the learning of associations between
      unfamiliar spoken words and their semantic referents, and whether it would vary
      across experimental conditions in first- and second-language word learning. A
      group of English monolinguals were recruited to learn 24 spoken disyllable
      Mandarin Chinese words in association with either familiar or novel objects as
      semantic referents. They also took a working memory task in which their ability
      to temporarily bind auditory-verbal and visual information was measured.
      Participants' performance on this task was uniquely linked to their learning and
      retention of words for both novel objects and for familiar objects. This suggests
      that, at least for spoken language, cross-modal working memory binding might play
      a similar role in second language-like (i.e., learning new words for familiar
      objects) and in more native-like situations (i.e., learning new words for novel
      objects). Our findings provide new evidence for the role of cross-modal working
      memory binding in L1 word learning and further indicate that early stages of
      picture-based word learning in L2 might rely on similar cognitive processes as in
      L1.

PMID- 28748448
TI  - Adding a brief self-report cognitive tool to the IHDS improves effectiveness of
      identifying patients with HIV-associated dementia in South Africa.
AB  - We compared the diagnostic accuracy of two brief screening tools (the
      International HIV Dementia Scale (IHDS), and the IHDS combined with a novel self
      report instrument, the HIV Cognitive Symptom Questionnaire (HCSQ)) with that of
      three brief neuropsychological screening batteries (a 2-, a 3-, and a 4-test
      battery, each consisting of standardized cognitive tests) in discriminating
      individuals with HIV-associated dementia (HAD) from those with milder forms of
      cognitive impairment. We analyzed data from 94 isiXhosa-speaking South African
      HIV-infected participants who were screened as part of a clinical trial
      evaluating adjunctive treatment in patients with moderate to severe HIV
      associated cognitive impairment. A comprehensive neuropsychological battery
      diagnosed 53% (50/94) of the participants with HAD. We evaluated the sensitivity
      and specificity for the screening tools and screening batteries. The brief
      screening tool performed better compared to the brief neuropsychology battery.
      The IHDS-HCSQ combination delivered 94% sensitivity and 63% specificity for HAD
      compared to the IHDS (74 and 70% at a cutoff of <=8) which offers a viable and
      quick way to screen for HAD in people living with HIV. It is easy to administer,
      is time- and cost-efficient, and it appears to be a better option, for these
      purposes, than brief neuropsychology batteries. It is viable for use in clinical,
      research, and workplace settings when identification of HIV-infected people with
      severe cognitive impairment is required.

PMID- 28748449
TI  - First report of persistent dengue-1-associated autoimmune neurological
      disturbance: neuromyelitis optica spectrum disorder.
AB  - Dengue virus (DENV) causes immune-mediated diseases. Neurological involvement
      represents a severe condition that is rarely observed in DENV-1 infection.
      Neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) are idiopathic immune
      mediated demyelinating syndromes of the central nervous system. We report a 17
      year-old female with oligosymptomatic DENV-1 viremia, diagnosed as NMOSD.
      Magnetic resonance imaging showed spinal cord and brainstem lesions. Antibody for
      aquaporin 4 was negative. DENV-1 RNA infection was detected by serial RT-PCR and
      confirmed by phylogenetic analysis in serum. Although there are some reports of
      NMO post-dengue infection, there are not any published accounts of NMOSD with
      coexistent and persistent DENV-1 infection.

PMID- 28748450
TI  - Replicating Health Economic Models: Firm Foundations or a House of Cards?
AB  - Health economic evaluation is a framework for the comparative analysis of the
      incremental health gains and costs associated with competing decision
      alternatives. The process of developing health economic models is usually
      complex, financially expensive and time-consuming. For these reasons, model
      development is sometimes based on previous model-based analyses; this endeavour
      is usually referred to as model replication. Such model replication activity may
      involve the comprehensive reproduction of an existing model or 'borrowing' all or
      part of a previously developed model structure. Generally speaking, the
      replication of an existing model may require substantially less effort than
      developing a new de novo model by bypassing, or undertaking in only a perfunctory
      manner, certain aspects of model development such as the development of a
      complete conceptual model and/or comprehensive literature searching for model
      parameters. A further motivation for model replication may be to draw on the
      credibility or prestige of previous analyses that have been published and/or used
      to inform decision making. The acceptability and appropriateness of replicating
      models depends on the decision-making context: there exists a trade-off between
      the 'savings' afforded by model replication and the potential 'costs' associated
      with reduced model credibility due to the omission of certain stages of model
      development. This paper provides an overview of the different levels of, and
      motivations for, replicating health economic models, and discusses the
      advantages, disadvantages and caveats associated with this type of modelling
      activity. Irrespective of whether replicated models should be considered
      appropriate or not, complete replicability is generally accepted as a desirable
      property of health economic models, as reflected in critical appraisal checklists
      and good practice guidelines. To this end, the feasibility of comprehensive model
      replication is explored empirically across a small number of recent case studies.
      Recommendations are put forward for improving reporting standards to enhance
      comprehensive model replicability.

PMID- 28748452
TI  - Single-cell transcriptomics reveals gene signatures and alterations associated
      with aging in distinct neural stem/progenitor cell subpopulations.
AB  - Aging associated cognitive decline has been linked to dampened neural
      stem/progenitor cells (NSC/NPCs) activities manifested by decreased
      proliferation, reduced propensity to produce neurons, and increased
      differentiation into astrocytes. While gene transcription changes objectively
      reveal molecular alterations of cells undergoing various biological processes,
      the search for molecular mechanisms underlying aging of NSC/NPCs has been
      confronted by the enormous heterogeneity in cellular compositions of the brain
      and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain
      NSC/NPCs themselves are not a homogenous population, making it even more
      difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both
      population-based and single cell transcriptome analyses of young and aged mouse
      forebrain ependymal and subependymal regions and comprehensive "big-data"
      processing, we report that NSC/NPCs reside in a rather inflammatory environment
      in aged brain, which likely contributes to the differentiation bias towards
      astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed
      that different aged NSC/NPC subpopulations, while all have reduced cell
      proliferation, use different gene transcription programs to regulate age
      dependent decline in cell cycle. Interestingly, changes in cell proliferation
      capacity are not influenced by inflammatory cytokines, but likely result from
      cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved
      in regulating age-dependent changes in the capacity for NSC/NPCs to undergo
      clonal expansion. Together this study is the first example of using population
      and single cell based transcriptome analyses to unveil the molecular interplay
      between different NSC/NPCs and their microenvironment in the context of the aging
      brain.

PMID- 28748451
TI  - The emerging role and targetability of the TCA cycle in cancer metabolism.
AB  - The tricarboxylic acid (TCA) cycle is a central route for oxidative
      phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and
      redox balance requirements. Despite early dogma that cancer cells bypass the TCA
      cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates
      that certain cancer cells, especially those with deregulated oncogene and tumor
      suppressor expression, rely heavily on the TCA cycle for energy production and
      macromolecule synthesis. As the field progresses, the importance of aberrant TCA
      cycle function in tumorigenesis and the potentials of applying small molecule
      inhibitors to perturb the enhanced cycle function for cancer treatment start to
      evolve. In this review, we summarize current knowledge about the fuels feeding
      the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage,
      common genetic alterations and deregulation of cycle enzymes, and potential
      therapeutic opportunities for targeting the TCA cycle in cancer cells. With the
      application of advanced technology and in vivo model organism studies, it is our
      hope that studies of this previously overlooked biochemical hub will provide
      fresh insights into cancer metabolism and tumorigenesis, subsequently revealing
      vulnerabilities for therapeutic interventions in various cancer types.

PMID- 28748453
TI  - Patterns of failure of diffuse large B-cell lymphoma patients after involved-site
      radiotherapy.
AB  - PURPOSE: Radiotherapy (RT) in combination with chemoimmunotherapy is highly
      efficient in the treatment of diffuse large B-cell lymphoma (DLBCL). This
      retrospective analysis evaluated the efficacy of the treatment volume and the
      dose concept of involved-site RT (ISRT). PATIENTS AND METHODS: We identified 60
      histologically confirmed stage I-IV DLBCL patients treated with multimodal
      cytotoxic chemoimmunotherapy and followed by consolidative ISRT from 2005-2015.
      Progression-free survival (PFS) and overall survival (OS) were estimated by
      Kaplan-Meier method. Univariate analyses were performed by log-rank test and Mann
      Whitney U-test. RESULTS: After initial chemoimmunotherapy (mostly R-CHOP;
      rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), 19
      (36%) patients achieved complete response (CR), 34 (64%) partial response (PR) or
      less. Excluded were 7 (12%) patients with progressive disease after
      chemoimmunotherapy. All patients underwent ISRT with a dose of 40 Gy. After a
      median follow-up of 44 months, 79% of the patients remained disease free, while
      21% presented with failure, progressive systemic disease, or death. All patients
      who achieved CR after chemoimmunotherapy remained in CR. Of the patients
      achieving PR after chemotherapy only 2 failed at the initial site within the ISRT
      volume. No marginal relapse was observed. Ann Arbor clinical stage I/II showed
      significantly improved PFS compared to stage III/IV (93% vs 65%; p <= 0.021).
      International Prognostic Index (IPI) score of 0 or 1 compared to 2-5 has been
      associated with significantly increased PFS (100% vs 70%; p <= 0.031).
      Postchemoimmunotherapy status of CR compared to PR was associated with
      significantly increased PFS (100% vs 68%; p <= 0.004) and OS (100% vs 82%; p <=
      0.026). Only 3 of 53 patients developed grade II late side effects, whereas grade
      III or IV side effects have not been observed. CONCLUSION: These data suggest
      that a reduction of the RT treatment volume from involved-field (IF) to involved
      site (IS) is sufficient because no marginal failures occurred. The concept of IS
      will likely reduce the risk for late sequelae of RT.

PMID- 28748454
TI  - Recurrence with pagetoid spread arising 17 years after surgery for intramucosal
      rectal cancer: a case report.
AB  - BACKGROUND: Perianal Paget's disease (pPD) is uncommon, with only about 180 cases
      documented in the literature. Anorectal carcinoma with pagetoid spread is even
      rarer. CASE PRESENTATION: An 81-year-old woman underwent rectal cancer
      extirpation with a transanal approach 17 years prior. She has since undergone two
      reoperations for local rectal cancer recurrence. Then, warts frequently appeared
      on the vulva on several occasions. Warts appeared on the vulva 1 year ago, which
      were diagnosed as pPD by biopsy. She underwent perineal tumor resection, and the
      final histological diagnosis was rectal cancer recurrence with pagetoid spread.
      The resected stump was positive for cancer cells, and tumor progression was
      rapid. She underwent additional abdominoperineal resection (Miles' operation)
      with lymph node dissection. However, disease progression was rapid and she died 7
      months after the Miles' operation. CONCLUSIONS: There are some case reports
      describing anorectal carcinoma with pagetoid spread, however, almost of all those
      cases were synchronous primary anorectal cancer. Here, we report the first case
      of metachronous recurrence rectal cancer with pagetoid spread arising 17 years
      after surgery.

PMID- 28748455
TI  - Resection of rectal cancer resembling submucosal tumor that was preoperatively
      diagnosed with endoscopic ultrasound-guided biopsy.
AB  - BACKGROUND: Colorectal cancer (CRC) resembling submucosal tumor (SMT; CRC/SMT) is
      very rare. Because its biopsy is challenging, accurate preoperative diagnosis is
      also very rare. CASE PRESENTATION: A 55-year-old woman with a high serum
      carcinoembryonic antigen level underwent a computed tomography colonoscopy, which
      showed extrinsic rectum compression. A coronal magnetic resonance image showed a
      4-cm low-intensity tumor between her rectum and sacrum. Endoscopic ultrasound
      (EUS) showed a 30-mm low-echoic lesion originating from the rectum. Pathological
      examination of specimen obtained with EUS-guided fine-needle aspiration biopsy
      (EUS-FNAB) revealed adenocarcinoma. Immunohistochemical staining showed the tumor
      to be positive for both CK20 and CDX2 and negative for CK7, indicating that it
      was a rectal cancer. We performed a laparoscopy-assisted low-anterior resection
      with dissection of the regional lymph nodes after eight chemotherapy cycles.
      Macroscopically, tumor was completely covered by normal rectal mucosa, but showed
      a 2-mm bulge on the mucosa. Histological examination revealed a moderately
      differentiated adenocarcinoma, mainly located at the subserosal layer and
      severely invaded to lymphatic and blood vessels. The mucosal layer was not
      exposed to the cancer components, and her postoperative course was uneventful.
      CONCLUSION: EUS-FNAB was useful in preoperative accurate diagnosis of this very
      rare tumor. We also review the literature and discuss CRC/SMT.

PMID- 28748456
TI  - Nonclinical Development of Combination Drugs.
AB  - We define "combination drugs" as "fixed-dose combinations" (FDCs), that is, two
      or more drugs (marketed or not) combined in a single pill or two or more separate
      drugs packaged together. FDCs have been available commercially for many years but
      only relatively recently have nonclinical development guidelines been released by
      a number of regulatory authorities and the World Health Organization; as yet
      there are no ICH guidelines specific to combination drugs. In general however,
      the ICH guidelines for monotherapy development provide a framework for FDC
      development. Depending on the type of drug combination (marketed drug/marketed
      drug; marketed drug/NME and NME/NME) the scope and complexity of toxicity studies
      will vary greatly. In all cases however, a key issue is the potential for
      pharmacokinetic and/or toxicologic interaction between the components. For a
      marketed drug/marketed drug combination a detailed review of the nonclinical data
      available may suffice, particularly when the components have a history of
      coadministration at about the same dose and ratio as that of the proposed
      combination. For a marketed drug/NME combination, in addition to a review of the
      data for the marketed drug, a full ICH program of studies will be required for
      the NME, and a study of up to 90-day duration (in one species) for the
      combination. With an NME/NME combination each component will require a full ICH
      battery of studies and a combination study in one species. In all cases
      additional studies may be needed to address data gaps. Given the many novel and
      complex issues which arise when developing FDCs we recommend that, whenever
      possible, the nonclinical study strategy is discussed with the regulatory
      authorities.

PMID- 28748457
TI  - Juvenile Nonclinical Safety Studies in Support of Pediatric Drug Development.
AB  - A pediatric assessment is now a required component of every drug marketing
      application in North America, Europe, and Japan, unless a waiver has been granted
      previously. Nonclinical juvenile toxicity studies are often required as part of
      this assessment. The protocols for juvenile toxicity studies are best devised in
      consultation with the regulatory authorities. It is important to submit the
      pediatric investigation plan (PIP) or pediatric study plan (PSP) early, in order
      not to delay the marketing authorization of the drug in adults. The choice of
      species and the design of juvenile toxicity studies are based on a series of
      complex considerations, including the therapeutic use of the drug, age at which
      children will be treated, duration of treatment, and potential age- or species
      specific differences in efficacy, pharmacokinetics, or toxicity.

PMID- 28748458
TI  - Procedures of Necropsy and Tissue Sampling.
AB  - Necropsy is a major step of most studies using laboratory animals. During
      necropsy, tissue and organ noticeable grossly changes should be recorded and
      critical tissue samples may be stored for the subsequent evaluation. It is
      therefore important that the personnel in charge of this key experimental step to
      be adequately trained and aware of the study endpoints.

PMID- 28748459
TI  - Tissue Sampling and Processing for Histopathology Evaluation.
AB  - Histological procedures aim at providing good-quality sections that can be used
      for a light microscopic evaluation of tissue. These are applicable to identify
      either spontaneous or diseases-induced changes. Routinely, tissues are fixed with
      neutral formalin 10%, embedded in paraffin, and manually sectioned with a
      microtome to obtain 4-5 MUm thick paraffin sections. Dewaxed sections are then
      stained with HE&S (hematoxylin-eosin and saffron) or can be used for other
      purposes (special stains, immunohistochemistry, in situ hybridization, etc.).
      During this processing, many steps and procedures are critical to ensure standard
      and interpretable sections. This chapter provides key recommendations to
      efficiently achieve this objective.

PMID- 28748460
TI  - Principles and Methods of Immunohistochemistry.
AB  - Immunohistochemical techniques detect antigens in tissue sections by means of
      immunological and chemical reactions. This technique is highly sensitive and
      specific and can detect a wide variety of antigens in multiple animal species.
      This chapter reviews common immunohistochemical methods used in the
      characterization of normal and pathologic tissue and the reagents used.
      Pretreatments such as blocking steps for endogenous activities and antigen
      retrieval are included. Standard procedures on formalin-fixed, paraffin-embedded
      tissues as well as method standardization for new antibodies and troubleshooting
      are emphasized.

PMID- 28748461
TI  - Applications of Mass Spectrometry Imaging for Safety Evaluation.
AB  - Mass spectrometry imaging (MSI) was first derived from techniques used in
      physics, which were then incorporated into chemistry followed by application in
      biology. Developed over 50 years ago, and with different principles to detect and
      map compounds on a sample surface, MSI supports modern biology questions by
      detecting biological compounds within tissue sections. MALDI (matrix-assisted
      laser desorption/ionization) imaging trend analysis in this field shows an
      important increase in the number of publications since 2005, especially with the
      development of the MALDI imaging technique and its applications in biomarker
      discovery and drug distribution. With recent improvements of statistical tools,
      absolute and relative quantification protocols, as well as quality and
      reproducibility evaluations, MALDI imaging has become one of the most reliable
      MSI techniques to support drug discovery and development phases. MSI allows to
      potentially address important questions in drug development such as "What is the
      localization of the drug and its metabolites in the tissues?", "What is the
      pharmacological effect of the drug in this particular region of interest?", or
      "Is the drug and its metabolites related to an atypical finding?" However, prior
      to addressing these questions using MSI techniques, expertise needs to be
      developed to become proficient at histological procedures (tissue preparation
      with frozen of fixed tissues), analytical chemistry, matrix application,
      instrumentation, informatics, and mathematics for data analysis and
      interpretation.

PMID- 28748462
TI  - In Vivo Rat T-Lymphocyte Pig-a Assay: Detection and Expansion of Cells Deficient
      in the GPI-Anchored CD48 Surface Marker for Analysis of Mutation in the
      Endogenous Pig-a Gene.
AB  - The Pig-a assay is being developed as an in vivo gene mutation assay for
      regulatory safety assessments. The assay is based on detecting mutation in the
      endogenous Pig-a gene of treated rats by using flow cytometry to measure changes
      in cell surface markers of peripheral blood cells. Here we present a methodology
      for demonstrating that phenotypically mutant rat T-cells identified by flow
      cytometry contain mutations in the Pig-a gene, an important step for validating
      the assay. In our approach, the mutant phenotype T-cells are sorted into
      individual wells of 96-well plates and expanded into clones. Subsequent
      sequencing of genomic DNA from the expanded clones confirms that the Pig-a assay
      detects exactly what it claims to detect-cells with mutations in the endogenous
      Pig-a gene. In addition, determining the spectra of Pig-a mutations provides
      information for better understanding the mutational mechanism of compounds of
      interest. Our methodology of combining phenotypic antibody labeling, magnetic
      enrichment, sorting, and single-cell clonal expansion can be used in
      genotoxicity/mutagenicity studies and in other general immunotoxicology research
      requiring identification, isolation, and expansion of extremely rare
      subpopulations of T-cells.

PMID- 28748463
TI  - Detection of In Vivo Mutation in the Pig-a Gene of Mouse Bone Marrow Erythroids.
AB  - Detection of in vivo mutation is important for evaluating the health risks
      associated with chemicals. The Pig-a in vivo gene mutation assay has been
      developed over the last decade for this purpose. Most approaches for the assay,
      however, measure cells with a Pig-a mutant phenotype in erythrocytes from the
      peripheral blood, with the mutations causing the phenotype being difficult to
      determine directly. This chapter describes a procedure for detecting mutations in
      the Pig-a gene of phenotypically mutant mouse bone marrow erythroids, the
      precursors of peripheral blood erythrocytes. The strategy for molecular analysis
      of Pig-a gene mutation includes enrichment of GPI-anchor deficient cells with a
      cell sorter followed by a cloning and sequencing of Pig-a cDNAs.

PMID- 28748464
TI  - The Use of Bacterial Repair Endonucleases in the Comet Assay.
AB  - The comet assay is a sensitive electrophoretic method for measuring DNA breaks at
      the level of single cells, used widely in genotoxicity experiments, in
      biomonitoring, and in fundamental research. Its sensitivity and range of
      application are increased by the incorporation of an extra step, after lysis of
      agarose-embedded cells, in which the DNA is digested with lesion-specific
      endonucleases (DNA repair enzymes of bacterial or phage origin). Enzymes with
      specificity for oxidized purines, oxidized pyrimidines, alkylated bases, UV
      induced cyclobutane pyrimidine dimers, and misincorporated uracil have been
      employed. The additional enzyme-sensitive sites, over and above the strand breaks
      detected in the standard comet assay, give a quantitative estimate of the number
      of specific lesions present in the cells.

PMID- 28748465
TI  - Automated Patch-Clamp Methods for the hERG Cardiac Potassium Channel.
AB  - The human Ether-a-go-go Related Gene (hERG) product has been identified as a
      central ion channel underlying both familial forms of elongated QT interval on
      the electrocardiogram and drug-induced elongation of the same QT segment. Indeed,
      reduced function of this potassium channel involved in the repolarization of the
      cardiac action potential can produce a type of life-threatening cardiac
      ventricular arrhythmias called Torsades de Pointes (TdP). Therefore, hERG
      inhibitory activity of newly synthetized molecules is a relevant structure
      activity metric for compound prioritization and optimization in medicinal
      chemistry phases of drug discovery. Electrophysiology remains the gold standard
      for the functional assessment of ion channel pharmacology. The recent years have
      witnessed automatization and parallelization of the manual patch-clamp technique,
      allowing higher throughput screening on recombinant hERG channels. However, the
      multi-well plate format of automatized patch-clamp does not allow visual
      detection of potential micro-precipitation of poorly soluble compounds. In this
      chapter we describe bench procedures for the culture and preparation of hERG
      expressing CHO cells for recording on an automated patch-clamp workstation. We
      also show that the sensitivity of the assay can be improved by adding a
      surfactant to the extracellular medium.

PMID- 28748466
TI  - Impedance Measurement in Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
AB  - Impedance-based measurement is a useful tool for assessing the contractility of
      plated cardiomyocytes in the context of early preclinical cardiosafety
      assessment. Induced pluripotent stem cell-derived cardiomyocytes (iPSCs) can be
      used for this purpose as these cells display similar electrochemical properties
      to primary cardiomyocytes and beat reliably and in synchronicity in culture. Here
      we describe a method for measuring the contractility of iPSCs using the
      xCELLigence RTCA impedance measurement system.

PMID- 28748467
TI  - Target Safety Assessment: Strategies and Resources.
AB  - An in-depth evaluation of target safety is an invaluable resource throughout drug
      discovery and development. The goal of a target safety evaluation is to identify
      potential unintended adverse consequences of target modulation, and to propose a
      risk evaluation and mitigation strategy to shepherd compounds through the
      discovery and development pipeline, to confirm and characterize unavoidable on
      target toxicities in a timely manner to assist in early program advancement
      decisions, and to anticipate, monitor, and manage potential clinical adverse
      events. The role of an experienced discovery toxicologist in synthesizing the
      available information into an actionable set of recommendations for a safety
      evaluation strategy is critical to its successful application in early discovery
      programs. This chapter presents a summary of some of the information types and
      sources that should be investigated, and approaches that can be taken to generate
      an early assessment of potential safety liabilities.

PMID- 28748468
TI  - NMR and MS Methods for Metabolomics.
AB  - Metabolomics, also often referred as "metabolic profiling," is the systematic
      profiling of metabolites in biofluids or tissues of organisms and their temporal
      changes. In the last decade, metabolomics has become more and more popular in
      drug development, molecular medicine, and other biotechnology fields, since it
      profiles directly the phenotype and changes thereof in contrast to other "-omics"
      technologies. The increasing popularity of metabolomics has been possible only
      due to the enormous development in the technology and bioinformatics fields. In
      particular, the analytical technologies supporting metabolomics, i.e., NMR, UPLC
      MS, and GC-MS, have evolved into sensitive and highly reproducible platforms
      allowing the determination of hundreds of metabolites in parallel. This chapter
      describes the best practices of metabolomics as seen today. All important steps
      of metabolic profiling in drug development and molecular medicine are described
      in great detail, starting from sample preparation to determining the measurement
      details of all analytical platforms, and finally to discussing the corresponding
      specific steps of data analysis.

PMID- 28748469
TI  - Protocols and Applications of Cellular Metabolomics in Safety Studies Using
      Precision-Cut Tissue Slices and Carbon 13 NMR.
AB  - Numerous xenobiotics are toxic to human and animal cells by interacting with
      their metabolism, but the precise metabolic step affected and the biochemical
      mechanism behind such a toxicity remain often unknown. In an attempt to reduce
      the ignorance in this field, we have developed a new approach called cellular
      metabolomics. This approach, developed in vitro, provides a panoramic view not
      only of the pathways involved in the metabolism of physiological substrates of
      any normal or pathological human or animal cell but also of the beneficial and
      adverse effects of xenobiotics on these metabolic pathways. Unlike many cell
      lines, precision-cut tissue slices, for which there is a renewed interest, remain
      metabolically differentiated for at least 24-48 h and allow to study the effect
      of xenobiotics during short-term and long-term incubations. Cellular metabolomics
      (or metabolic flux analysis), which combines enzymatic and carbon 13 NMR
      measurements with mathematical modeling of metabolic pathways, is illustrated in
      this brief chapter for studying the effect of insulin on glucose metabolism in
      rat liver precision-cut slices and of valproate on glutamine metabolism in human
      renal cortical precision-cut slices. The use of very small amounts of test
      compounds allows to predict their toxic effect and eventually their beneficial
      effects very early in the research and development processes. Cellular
      metabolomics is complementary to other omics approaches, but, unlike them,
      provides functional, mechanistic, and dynamic pieces of information by measuring
      enzymatic fluxes.

PMID- 28748470
TI  - Statistical Analysis of Quantitative RT-PCR Results.
AB  - Quantitative real-time reverse transcription polymerase chain reaction (RT-PCR)
      represents a benchmark technology in the detection and quantification of mRNA.
      Yet, accurate results cannot be realized without proper statistical analysis of
      RT-PCR data. Here we examine some of the issues concerning RT-PCR experiments
      that would benefit from rigorous statistical treatment including normalization,
      quantification, efficiency estimation, and sample size calculations. Examples are
      used to illustrate the methods.

PMID- 28748471
TI  - Evaluation of Mitochondrial Respiration in Cultured Rat Hepatocytes.
AB  - Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver
      injury and other serious side effects, such as lactic acidosis and
      rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can
      be performed in order to determine if drugs can disturb mitochondrial fatty acid
      oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete
      hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial
      permeability transition pore (MPT). Among these investigations, mitochondrial
      respiration is a relatively easy test to measure the potential toxicity of a
      drug. The use of cells instead of isolated mitochondria allows one to test the
      toxic effect of a parent compound and its metabolites. The use of rat hepatocytes
      can detect drugs involved in drug-induced liver injuries (DILI). The method
      consists in measuring oxygen consumption by using a Clark electrode in a chamber
      containing a suspension of hepatocytes preincubated with drug.

PMID- 28748472
TI  - FETAX Assay for Evaluation of Developmental Toxicity.
AB  - The frog embryo teratogenesis assay Xenopus (FETAX) test is a development
      toxicity screening test. Due to the small amount of compound needed and the
      capability to study organogenesis in a short period of time (96 h), FETAX test
      constitutes an efficient development toxicity alert test when performed early in
      drug safety development. The test is conducted on fertilized Xenopus laevis mid
      blastula-stage eggs over the organogenesis period. Compound teratogenic potential
      is determined after analysis of the mortality and malformation observations on
      larvae. In parallel, FETAX test provides also information concerning embryotoxic
      effect based on larva length.

PMID- 28748473
TI  - Evaluation of Embryotoxicity Using the Zebrafish Model.
AB  - The embryonic zebrafish model offers the power of whole-animal investigations
      (e.g., intact organism, functional homeostatic feedback mechanisms, and
      intercellular signaling) with the convenience of cell culture (e.g., cost- and
      time-efficient, minimal infrastructure, small quantities of solutions required).
      The model system overcomes many of the current limitations in rapid to high
      throughput screening of drugs/compounds and casts a broad net to rapidly evaluate
      integrated system effects. Additionally, it is an ideal platform to follow up
      with targeted studies aimed at the mechanisms of toxic action. Exposures are
      carried out in multi-well plates so minimal solution volumes are required for the
      assessments. Numerous morphological, developmental, and behavioral endpoints can
      be evaluated noninvasively due to the transparent nature of the embryos.

PMID- 28748474
TI  - Absolute Quantification of Toxicological Biomarkers via Mass Spectrometry.
AB  - With the advent of "-omics" technologies there has been an explosion of data
      generation in the field of toxicology, as well as many others. As new candidate
      biomarkers of toxicity are being regularly discovered, the next challenge is to
      validate these observations in a targeted manner. Traditionally, these validation
      experiments have been conducted using antibody-based technologies such as Western
      blotting, ELISA, and immunohistochemistry. However, this often produces a
      significant bottleneck as the time, cost, and development of successful
      antibodies are often far outpaced by the generation of targets of interest. In
      response to this, there recently have been several developments in the use of
      triple quadrupole (QQQ) mass spectrometry (MS) as a platform to provide
      quantification of proteins. This technology does not require antibodies; it is
      typically less expensive and quicker to develop assays and has the opportunity
      for more accessible multiplexing. The speed of these experiments combined with
      their flexibility and ability to multiplex assays makes the technique a valuable
      strategy to validate biomarker discovery.

PMID- 28748475
TI  - Next-Generation Sequencing to Investigate Urinary microRNAs from Macaca
      fascicularis (Cynomolgus Monkey).
AB  - Advanced sequencing technologies like next-generation sequencing (NGS) not only
      detect microRNAs (miRNAs) in biological samples but also facilitate de novo
      identification of miRNAs. Using an Ion Torrent's Ion Proton System, here we
      described miRNAs sequencing of urine samples collected from Macaca fascicularis
      (Cynomolgus monkey) to investigate miRNAs as potential novel biomarkers of
      nephrotoxicity in this species. Urinary miRNA sequencing methodologies described
      here include (a) urinary exosomal RNA isolation, (b) sequencing library
      preparation, (c) sequencing template preparation, and (d) template library
      sequencing using Ion Proton System. The sequencing method presented in this study
      serves as a valuable resource in the identification of novel urinary miRNAs in M.
      fascicularis.

PMID- 28748476
TI  - Quantitative RT-PCR for MicroRNAs in Biofluids.
AB  - MicroRNAs in biofluids hold great promise as minimally invasive diagnostic
      biomarkers for a wide range of diseases and biological processes. One of the most
      sensitive technologies for detection and measuring expression levels of microRNA
      is quantitative RT-PCR. However, quantification of microRNA in biofluid samples
      is challenging in many ways. Biofluids contain low levels of RNA and high levels
      of inhibitors of enzymatic processes like reverse transcription and PCR.
      Furthermore, biofluids are susceptible to many preanalytical variables. Here we
      describe procedures developed to address these challenges, which include highly
      sensitive and accurate microRNA detection methods, combined with optimized
      protocols for sample handling and preparation, and extensive quality control (QC)
      procedures.

PMID- 28748477
TI  - Chromogenic In Situ Hybridization Methods for microRNA Biomarker Monitoring of
      Drug Safety and Efficacy.
AB  - Disease research and treatment development have turned to the impact and utility
      of microRNA. The dynamic and highly specific expression of these molecular
      regulators can be used to predict and monitor disease progression as well as
      therapeutic treatment efficacy and safety, thus aiding decisions in patient care.
      In situ hybridization (ISH) of biopsy material has become a routine clinical
      pathology procedure for monitoring gene structure, expression, and sample
      characterization. For ribonucleic acid (RNA), determining cell source and level
      of expression of these biomarkers gives insight into the cellular function and
      physiopathology. Identification and monitoring of microRNA biomarkers are made
      possible through locked nucleic acid (LNA)TM-based detection probes. LNATM
      enhances the sensitivity and specificity of target binding, most profoundly so
      for the short, highly similar, microRNA sequences. We present a robust 1-day ISH
      protocol for formalin-fixed, paraffin-embedded (FFPE) tissue sections based on
      microRNA-specific LNATM detection probes which can be labeled with digoxigenin
      (DIG) or 6-carboxyfluorescein (FAM) and detected through enzyme-linked specific
      antibodies that catalyze substrates into deposited chromogen products at the
      target RNA site. The variety of haptens and detection reagents in combination
      with LNATM chemistry offer flexibility and ease to multiple target assessment of
      therapeutic response.

PMID- 28748478
TI  - Urine Exosome Isolation and Characterization.
AB  - Exosomes are nanometer-scale, membrane-enclosed vesicles that can potentially be
      used to detect nephrotoxicity, and reveal the subsequent response of the kidney.
      Epithelial cells of every nephron segment can contribute to the urinary exosome
      population, which is rich in potential biomarkers, including membrane proteins
      such as transporters and receptors, transcription factors, and microRNAs. These
      exosomal biomarkers may be up- or downregulated upon nephrotoxicant exposure.
      Exosome isolation is an area of ongoing research. Although faster and simpler
      methods have been developed, ultracentrifugation remains a mainstay for
      purification. A single ultracentrifugation step provides an enriched preparation
      suitable for biomarker discovery, and a second ultracentrifugation on a
      sucrose/D2O cushion provides the purest exosome preparation currently available
      and may be preferred for bioactivity assays. The concentration of exosomes can be
      determined using Nanosight Nanoparticle Tracking Analysis and their contents
      studied with a variety of approaches including western blots for proteins and RT
      qPCR for microRNAs.

PMID- 28748479
TI  - STING Signaling in Cancer Cells: Important or Not?
AB  - Stimulator of interferon genes (STING) is an adaptor protein that plays an
      important role in the activation of type I interferons in response to cytosolic
      nucleic acid ligands. Recent evidence indicates involvement of the STING pathway
      in the induction of antitumor immune response. Therefore, STING agonists are now
      being extensively developed as a new class of cancer therapeutics. However,
      little is known about the consequences of activated STING-mediated signaling in
      cancer cells on the efficacy of the antitumor treatment. It has been shown that
      activation of the STING-dependent pathway in cancer cells can result in tumor
      infiltration with immune cells and modulation of the anticancer immune response.
      Understanding the function of STING pathway in cancer cells might provide
      important insights into the development of effective therapeutic strategies. This
      review focuses on the role of STING pathway in cancer cells, the largely unknown
      topic that has recently emerged to be important in the context of STING-mediated
      antitumor responses.

PMID- 28748480
TI  - Investigation of the effects of starch on the physical and biological properties
      of polyacrylamide (PAAm)/starch nanofibers.
AB  - Here, we report the development of a new polyacrylamide (PAAm)/starch nanofibers'
      blend system and highlight its potential as substrate for efficient enzyme
      immobilization. PAAm was synthesized and blended with starch. The final blend was
      then electrospun into nanofibers. The response surface methodology was used to
      analyze the parameters that control nanofiber's diameter. Electrospun mat was
      then modified either by cross-linking or phytase immobilization using silane
      coupling agent and glutaraldehyde chemistry. Physico-chemical properties of
      blends were investigated using spectroscopic and thermal studies. The evaluation
      of immobilized enzyme kinetics on both pure and the starch blended PAAm
      nanofibers was performed using Michaelis-Menten kinetic curves. Fourier transform
      infrared spectroscopy results along with differential scanning and X-ray
      diffraction confirmed that blending was successfully accomplished. TGA analysis
      also demonstrated that the presence of starch enhances the thermal degradability
      of PAAm nanofibers. Finally, it was shown that addition of starch to PAAm
      increases the efficacies of enzyme loading and, therefore, significantly enhances
      the activity as well as kinetics of the immobilized enzyme on electrospun blend
      mats.

PMID- 28748482
TI  - Morphological Analysis of Biocompatibility of Autologous Bone Marrow Mononuclear
      Cells with Synthetic Polyethylene Terephthalate Scaffold.
AB  - We studied the properties of a tissue-engineered trachea consisting of a
      polyethylene terephthalate scaffold populated with autologous bone marrow
      mononuclear cells. The tissue-engineered constructs were obtained before surgery,
      during the postoperative period, and during autopsy. Cytomorphological analysis
      during the postoperative period showed the presence of mesenchymal stem cells on
      the inner surface of the implant on day 3 after surgery and cells of the
      respiratory epithelium on day 10-14. In autopsy samples, single epithelial cells,
      endothelial cells, and basal cells were found. Biocompatibility of the tissue
      engineered trachea with autologous mononuclear cells of the patient was
      demonstrated.

PMID- 28748481
TI  - Public health relevance of drug-nutrition interactions.
AB  - The public health relevance of drug-nutrition interactions is currently highly
      undervalued and overlooked. This is particularly the case for elderly persons
      where multi-morbidity and consequently polypharmacy is very common. Vitamins and
      other micronutrients have central functions in metabolism, and their interactions
      with drugs may result in clinically relevant physiological impairments but
      possibly also in positive effects. On 12 April 2016, the University Medical
      Center Groningen (The Netherlands), as part of its Healthy Ageing program,
      organized a workshop on the public health relevance of drug-nutrient
      interactions. In this meeting, experts in the field presented results from recent
      studies on interactions between pharmaceuticals and nutrients, and discussed the
      role of nutrition for elderly, focusing on those persons receiving pharmaceutical
      treatment. This paper summarizes the proceedings of the symposium and provides an
      outlook for future research needs and public health measures. Since food, pharma
      and health are closely interconnected domains, awareness is needed in the medical
      community about the potential relevance of drug-nutrition interactions. Experts
      and stakeholders should advocate for the integration of drug-nutrition
      evaluations in the drug development process. Strategies for the individual
      patients should be developed, by installing drug review protocols, screening for
      malnutrition and integrating this topic into the general medical advice.

PMID- 28748483
TI  - Expression of MicroRNA-146a and MicroRNA-155 in Placental Villi in Early- and
      Late-Onset Preeclampsia.
AB  - We studied the expression of microRNA-146a and microRNA-155 in placental villi
      from 18 women (26-39 weeks of gestation) of reproductive age with early- or late
      onset preeclampsia. The reference group consisted of women with physiological
      pregnancy and full-term gestation and with preterm birth after caesarian section
      on gestation week 26-31. MicroRNA-146a and microRNA-155 were detected by in situ
      hybridization with digoxigenin on paraffin sections. It was found that the
      expression of microRNA-146a in both syncytiotrophoblast of the intermediate villi
      and syncytial knots was lower at late-onset preeclampsia than at physiologic
      pregnancy of full-term period (p=0.037 and p=0.001 respectively). The expression
      of microRNA-155 in syncytiotrophoblast of intermediate placental villi in early
      onset preeclampsia was higher than in group with preterm delivery (p=0.003).
      However, in syncytiotrophoblast of intermediate villi and in syncytial knots, the
      expression of microRNA-155 was lower at late-onset preeclampsia in comparison
      with full-term physiological pregnancy (p=0.005). In addition, the expression of
      microRNA-146a and microRNA-155 did not increase in the later terms in
      preeclampsia, while in the reference groups demonstrating gradual increase in the
      expression of these markers with increasing gestational age. Expression microRNA
      146a and microRNA-155 little differed in early- and late-onset preeclampsia.
      These findings suggest that different variants of preeclampsia are probably
      characterized by common pathogenetic pathways. Damaged trophoblast cannot
      maintain of microRNAs synthesis at the required level, which determines the
      formation of a vicious circle in preeclampsia and further progression of the
      disease.

PMID- 28748484
TI  - Assessing for suicidal behavior in youth using the Achenbach System of
      Empirically Based Assessment.
AB  - This study investigated the clinical utility of the Achenbach System of
      Empirically Based Assessment (ASEBA) for identifying youth at risk for suicide.
      Specifically, we investigated how well the Total Problems scores and the sum of
      two suicide-related items (#18 "Deliberately harms self or attempts suicide" and
      #91 "Talks about killing self") were able to distinguish youth with a history of
      suicidal behavior. Youth (N = 1117) aged 5-18 were recruited for two studies of
      mental illness. History of suicidal behavior was assessed by semi-structured
      interviews (K-SADS) with youth and caregivers. Youth, caregivers, and a primary
      teacher each completed the appropriate form (YSR, CBCL, and TRF, respectively) of
      the ASEBA. Areas under the curve (AUCs) from ROC analyses and diagnostic
      likelihood ratios (DLRs) were used to measure the ability of both Total Problems
      T scores, as well as the summed score of two suicide-related items, to identify
      youth with a history of suicidal behavior. The Suicide Items from the CBCL and
      YSR performed well (AUCs = 0.85 and 0.70, respectively). The TRF Suicide Items
      did not perform better than chance, AUC = 0.45. The AUCs for the Total Problems
      scores were poor-to-fair (0.33-0.65). The CBCL Suicide Items outperformed all
      other scores (ps = 0.04 to <0.0005). Combining the CBCL and YSR items did not
      lead to incremental improvement in prediction over the CBCL alone. The sum of two
      questions from a commonly used assessment tool can offer important information
      about a youth's risk for suicidal behavior. The low burden of this approach could
      facilitate wide-spread screening for suicide in an increasingly at-risk
      population.

PMID- 28748485
TI  - Early onset first episode psychosis: dimensional structure of symptoms, clinical
      subtypes and related neurodevelopmental markers.
AB  - Despite the growing interest in a dimensional approach to the assessment of
      symptoms and clinically relevant phenomena in schizophrenia spectrum disorders,
      very few studies, to date, have examined the dimensional structure of symptoms in
      early onset first episode psychosis. In the present study, we assessed a sample
      of 60 children and adolescents of both sexes with first episode schizophrenia
      spectrum psychosis. A principal component analysis (PCA) of the Positive and
      Negative Syndrome Scale (PANSS) was performed and the factors obtained were used
      to carry out a cluster analysis. Sex, age of onset before or after 13, markers of
      early neurodevelopmental impairment and intellectual disabilities were considered
      as variables to characterized potential clinical subtypes, applying a one-way
      analysis of variance. Four factors were extracted ("negative symptoms",
      "delusions", "conceptual disorganization" and "paranoid/hostility"), each of them
      identifying a discrete clinical subtype of patients. No difference was found
      among the groups about sex and age of onset; delayed speech/language development
      was significantly associated with the "delusions" subtype and both "conceptual
      disorganization" and "delusions" subtypes showed a lower intelligence quotient
      (IQ). The four factors model we presented highlights "negative symptoms" as the
      most consistent factor; among positive symptoms, unusual thought content and
      conceptual disorganization resulted more distinctive of psychosis, at this age
      range, than perceptual abnormalities. Evolutionary trajectories of the four
      clinical subtypes we obtained seem to be influenced by cognitive and
      neurodevelopmental impairment rather than sex and age of onset.

PMID- 28748486
TI  - Nonlinear processing of a multicomponent communication signal by combination
      sensitive neurons in the anuran inferior colliculus.
AB  - Diverse animals communicate using multicomponent signals. How a receiver's
      central nervous system integrates multiple signal components remains largely
      unknown. We investigated how female green treefrogs (Hyla cinerea) integrate the
      multiple spectral components present in male advertisement calls. Typical calls
      have a bimodal spectrum consisting of formant-like low-frequency (~0.9 kHz) and
      high-frequency (~2.7 kHz) components that are transduced by different sensory
      organs in the inner ear. In behavioral experiments, only bimodal calls reliably
      elicited phonotaxis in no-choice tests, and they were selectively chosen over
      unimodal calls in two-alternative choice tests. Single neurons in the inferior
      colliculus of awake, passively listening subjects were classified as combination
      insensitive units (27.9%) or combination-sensitive units (72.1%) based on
      patterns of relative responses to the same bimodal and unimodal calls.
      Combination-insensitive units responded similarly to the bimodal call and one or
      both unimodal calls. In contrast, combination-sensitive units exhibited both
      linear responses (i.e., linear summation) and, more commonly, nonlinear responses
      (e.g., facilitation, compressive summation, or suppression) to the spectral
      combination in the bimodal call. These results are consistent with the hypothesis
      that nonlinearities play potentially critical roles in spectral integration and
      in the neural processing of multicomponent communication signals.

PMID- 28748487
TI  - Predictions of Speech Chimaera Intelligibility Using Auditory Nerve Mean-Rate and
      Spike-Timing Neural Cues.
AB  - Perceptual studies of speech intelligibility have shown that slow variations of
      acoustic envelope (ENV) in a small set of frequency bands provides adequate
      information for good perceptual performance in quiet, whereas acoustic temporal
      fine-structure (TFS) cues play a supporting role in background noise. However,
      the implications for neural coding are prone to misinterpretation because the
      mean-rate neural representation can contain recovered ENV cues from cochlear
      filtering of TFS. We investigated ENV recovery and spike-time TFS coding using
      objective measures of simulated mean-rate and spike-timing neural representations
      of chimaeric speech, in which either the ENV or the TFS is replaced by another
      signal. We (a) evaluated the levels of mean-rate and spike-timing neural
      information for two categories of chimaeric speech, one retaining ENV cues and
      the other TFS; (b) examined the level of recovered ENV from cochlear filtering of
      TFS speech; (c) examined and quantified the contribution to recovered ENV from
      spike-timing cues using a lateral inhibition network (LIN); and (d) constructed
      linear regression models with objective measures of mean-rate and spike-timing
      neural cues and subjective phoneme perception scores from normal-hearing
      listeners. The mean-rate neural cues from the original ENV and recovered ENV
      partially accounted for perceptual score variability, with additional variability
      explained by the recovered ENV from the LIN-processed TFS speech. The best model
      predictions of chimaeric speech intelligibility were found when both the mean
      rate and spike-timing neural cues were included, providing further evidence that
      spike-time coding of TFS cues is important for intelligibility when the speech
      envelope is degraded.

PMID- 28748488
TI  - Association between paraspinal muscle morphology, clinical symptoms and
      functional status in patients with lumbar spinal stenosis.
AB  - PURPOSE: Lumbar spinal stenosis (LSS) is a disabling condition associated with
      narrowing of the spinal canal or vertebral foramina. Paraspinal muscle atrophy
      and fatty infiltration have been reported in patients with chronic LBP and disc
      herniation. However, very few imaging studies have examined paraspinal muscle
      morphology and composition in patients with LSS. The purpose of this study was to
      investigate the association of paraspinal muscle size, composition and asymmetry
      with functional status in patients with LSS. METHODS: Thirty-six patients
      diagnosed with LSS at L4-L5 with neurogenic claudication were included.
      Paraspinal muscle measurements were obtained from axial T2-weighted MR images,
      bilaterally, at the level of the superior and inferior vertebral endplates of L5.
      Muscle measurements of interest included: total cross-sectional area (CSA),
      functional CSA (FCSA), the ratio of FCSA to CSA (FCSA/CSA) as an indicator of
      muscle composition, and relative % asymmetry in muscle CSA. The association
      between muscle parameters and other patient characteristics with function as
      indicated from Oswestry Disability Index (ODI) scores and pain interference
      status was investigated. RESULTS: Greater multifidus muscle fatty infiltration
      (e.g., lower FCSA/CSA) and lower psoas relative CSA were associated with lower
      function (higher ODI and pain interference scores) in univariable and
      multivariable analyses. There was no association between the different muscle
      parameters and stenosis severity or back or leg pain duration or severity.
      CONCLUSIONS: Our findings suggest an association of multifidus muscle fatty
      infiltration and psoas muscle size with functional status in patients diagnosed
      with LSS. Future prospective studies are needed to evaluate whether such muscle
      parameters are associated with prognosis and functional recovery following
      surgical treatment.

PMID- 28748489
TI  - Hamstring autograft maturation is superior to tibialis allograft following
      anatomic single-bundle anterior cruciate ligament reconstruction.
AB  - PURPOSE: Using second-look arthroscopy, graft maturation was investigated and
      compared between hamstring (HA) autografts and tibialis anterior (TA) allografts
      after anatomic single-bundle anterior cruciate ligament reconstruction (ACLR).
      METHODS: Fifty-six patients who underwent second-look arthroscopy after anatomic
      single-bundle ACLR with either HA autografts (26, HA group) or TA allografts (30,
      TA group) from 2007 to 2016 were retrospectively reviewed. Graft maturation on
      second-look arthroscopy was evaluated in terms of four parameters: graft
      integrity (tear), synovial coverage, graft tension, and graft vascularization.
      Each parameter received a maximum of two points, depending on the status of the
      reconstructed graft. The total graft maturation score was calculated as the sum
      of the parameter scores. The total graft maturation and individual parameter
      scores were compared between the two groups. RESULTS: The mean time from ACLR to
      second-look arthroscopy was 22.5 +/- 7.8 months. The maturation scores in the HA
      group were significantly better in terms of graft integrity (p = 0.041), graft
      tension (p = 0.010), and graft vascularization (p = 0.024), whereas the graft
      synovial coverage score was not significantly different. The total graft
      maturation score of the HA group was significantly higher than that of the TA
      group (6.3 +/- 0.4 vs. 4.9 +/- 0.3, p = 0.013). CONCLUSIONS: This study shows the
      superior graft maturation of HA autografts compared with that of TA allografts at
      a mean follow-up of 22.5 +/- 7.8 months after anatomic single-bundle ACLR. When
      anatomic ACLR using soft tissue graft is planned, HA autograft is recommended
      rather than soft tissue allograft, especially in young and active patients. LEVEL
      OF EVIDENCE: Retrospective cohort review, Level III.

PMID- 28748490
TI  - A simple cinch is superior to a locking loop for meniscus root repair: a human
      biomechanical comparison of suture constructs in a transtibial pull-out model.
AB  - PURPOSE: To determine the cyclic displacement and ultimate failure loads of two
      clinically relevant suture configurations for repair of medial and lateral
      meniscus root tears. METHODS: A total of 10 matched pair fresh-frozen, human
      meniscus specimens were randomly assigned to either simple cinch or locking loop
      meniscus-suture fixation techniques for transtibial pull-out repair in either
      medial (n = 10 matched pairs) or lateral (n = 10 matched pairs) meniscal root
      tears. The menisci were subjected to cyclic tensioning at 10-30 N for 1000 cycles
      at 0.5 Hz, and then post-cycling load to failure was performed at a tensile rate
      of 0.5 mm/s. RESULTS: For both the medial and lateral meniscus, there was
      significantly less displacement with the cinch stitch at 100, 500 and 1000 cycle
      counts (p < 0.05). In respect to ultimate load, there was no significant
      difference in type of repair between the two suture configurations. When
      comparing ultimate load to failure from the medial to the lateral side, the
      ultimate load to failure was significantly greater for both suture configurations
      in the lateral meniscus root repair (p < 0.05). However, there was no significant
      difference in cyclic displacement between the medial and lateral meniscus.
      CONCLUSIONS: The cinch stitch was significantly better at resisting displacement
      compared to the locking loop stitch configuration, and had similar ultimate load
      to failure. The lateral meniscus root repair construct has higher failure loads
      compared to the medial meniscus, independent of suture configuration.

PMID- 28748491
TI  - Polyurethane meniscal scaffolds lead to better clinical outcomes but worse
      articular cartilage status and greater absolute meniscal extrusion.
AB  - PURPOSE: Implantation of polyurethane (PU) meniscal scaffolds has become a
      popular procedure to provide a scaffold for vessel ingrowth and meniscal tissue
      regeneration in patients with partial meniscal defects. However, it is unclear
      whether PU meniscal scaffolds lead to better clinical and magnetic resonance
      imaging (MRI) outcomes post-operatively. This meta-analysis compared the clinical
      and MRI outcomes in patients with partial meniscal defects treated with PU
      meniscal scaffolds. METHODS: This meta-analysis reviewed all studies that
      assessed Lysholm score, International Knee Documentation Committee (IKDC) score,
      visual analogue scale (VAS) for pain, Tegner score, Knee Injury and
      Osteoarthritis Outcomes Score (KOOS), articular cartilage (AC), absolute meniscal
      extrusion (AME), morphology and size (MS), signal intensity (SI) of meniscal
      implant, and interface of the implant-residual meniscus complex (IIRMC) in
      patients with partial meniscal defects treated with PU meniscal scaffolds.
      RESULTS: Eighteen studies were included in the meta-analysis. The proportion of
      patients who evaluated MS (OR 0.71, 95% CI 0.38-1.33; n.s.), SI (OR 1.07, 95% CI
      0.53-2.18; n.s.), and IIRMC (OR 1.00, 95% CI 0.33-3.06; n.s.) did not differ
      significantly between baseline and final follow-up. However, AC (OR 0.31, 95% CI
      0.11-0.84; P = 0.02) and AME (OR 0.05, 95% CI 0.01-0.18; P < 0.00001) worsened
      between baseline and final follow-up. Conversely, Lysholm score (95% CI -1.87 to 
      1.07; P < 0.00001), IKDC score (95% CI -2.19 to -1.08; P < 0.00001), VAS for pain
      (95% CI -2.29 to -1.07; P < 0.00001), Tegner score (95% CI -0.76 to -0.15; P =
      0.003), and overall KOOS (95% CI -29.48 to -23.17; P < 0.00001) were
      significantly greater at final follow-up when compared to baseline. CONCLUSION:
      This meta-analysis found no significant differences in the tested MRI parameters,
      including MS, SI, and IIRMC. However, AC and AME worsened between baseline and
      final follow-up. Conversely, patients treated with PU meniscal scaffolds showed
      significant functional improvement and pain relief when compared with baseline
      scores. Thus, PU meniscal scaffolds appear to be a viable alternative for
      patients with partial meniscal defects, although further studies are needed to
      determine whether worsened AC and AME are clinically relevant. In particular,
      precise measurement of PU meniscal scaffolds in combination with thorough
      investigation of the baseline articular cartilage status and meniscal defect size
      may be effective for pain relief or functional improvement in patients with PU
      meniscal scaffold implantation. LEVEL OF EVIDENCE: III.

PMID- 28748492
TI  - Calcium phosphate-hybridized tendon grafts reduce femoral bone tunnel enlargement
      in anatomic single-bundle ACL reconstruction.
AB  - PURPOSE: This study aimed to clarify the effect of calcium phosphate (CaP)
      hybridized tendon grafting versus unhybridized tendon grafting on the
      morphological changes to the bone tunnels at the aperture 1 year after anatomic
      single-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: Seventy
      three patients were randomized to undergo the CaP (n = 37) or the conventional
      method (n = 36). All patients underwent computed tomography (CT) evaluation 1
      week and 1 year post-operatively. The femoral and tibial tunnels at the aperture
      were evaluated on reconstructed 3D CT images. Changes in the cross-sectional area
      (CSA) and diameters of the femur and the tibia, and the translation rate of the
      tunnel walls and the morphological changes of both tunnels were assessed.
      RESULTS: There was a significant reduction in the increase in the CSA and the
      anterior-posterior and proximal-distal tunnel diameters on the femoral side in
      the CaP group as compared with the conventional group. On the femoral side, the
      translation rate of the posterior wall was significantly larger in the CaP group
      than in the conventional group, whereas the translation rate of the distal wall
      was significantly smaller in the CaP group than in the conventional group.
      CONCLUSIONS: As compared with the conventional method, the CaP-hybridized tendon
      graft reduced bone tunnel enlargement on the femoral side 1 year after anatomic
      single-bundle ACL reconstruction due to an anterior shift of the posterior wall
      and reduced distal shift in the femoral bone tunnel. Clinically, the CaP
      hybridized tendon grafts can prevent femoral bone tunnel enlargement in anatomic
      single-bundle ACL reconstruction. LEVEL OF EVIDENCE: I.

PMID- 28748493
TI  - Cost-effectiveness of preimplantation genetic screening for women older than 37
      undergoing in vitro fertilization.
AB  - PURPOSE: Adding preimplantation genetic screening to in vitro fertilization has
      been shown to increase live birth rate in women older than 37. However,
      preimplantation genetic screening is an expensive procedure. Information on the
      cost-effectiveness of preimplantation genetic screening can help inform clinical
      decision making. METHODS: We constructed a decision analytic model for a
      hypothetical fresh, autologous in vitro fertilization cycle (with versus without
      preimplantation genetic screening) for women older than age 37 who had a
      successful oocyte retrieval and development of at least one blastocyst. The model
      incorporated probability and cost estimates of relevant clinical events based on
      data from published literature. Sensitivity analyses were performed to examine
      the impact of changes in model input parameters. RESULTS: In base-case analysis,
      IVF-PGS offered a 4.2 percentage point increase in live birth rate for an
      additional cost of $4509, yielding an incremental cost-effectiveness ratio (ICER)
      of $105,489 per additional live birth. This ICER was below the expected cost of
      $145,063 for achieving one live birth with IVF (assuming an average LBR of 13.4%
      and $19,415 per cycle for this patient population). Sensitivity analysis
      suggested that ICER improved substantially with decreases in PGS cost and
      increases in PGS effectiveness. Monte Carlo simulation showed PGS to be cost
      effective in 93.9% of iterations at an acceptability cutoff of $145,063.
      CONCLUSIONS: Considering the expected cost of achieving one live birth with IVF,
      PGS is a cost-effective strategy for women older than 37 undergoing IVF.
      Additional research on patients' willingness-to-pay per live birth would further
      inform our understanding regarding the cost-effectiveness of PGS.

PMID- 28748494
TI  - High glucose stimulates cell proliferation and Collagen IV production in rat
      mesangial cells through inhibiting AMPK-KATP signaling.
AB  - PURPOSE: The present study investigated the putative mechanisms underlying
      effects of KATP channel on high glucose (HG)-induced mesangial cell proliferation
      and tissue inhibitors of metalloproteinases (TIMP)-2 and Collagen IV production.
      METHODS: Rat mesangial cells were subjected to whole cell patch clamp to record
      the KATP channel currents under high glucose (HG, 30 mM) condition. Cell
      proliferation was measured using a CCK-8 assay. The production of TIMP-2 and
      Collagen IV and AMP-activated protein kinase (AMPK)-signaling pathway activity
      was assessed by ELISA and Western blotting, respectively. AMPK agonist (AICAR)
      was used to analyze the role of this kinase. The expression of KATP subunit
      (Kir6.1, Kir6.2, SUR1, SUR2A and SUR2B) was examined using quantitative real-time
      PCR (RT-PCR). RESULTS: We found that HG was significant decreases in the
      expression of Kir6.1, SUB2A and SUB2B, three subunits of KATP, TIMP-2 production,
      KATP channel activity and AMPK activity, while it promoted the cell proliferation
      and Collagen IV production in rat mesangial cells. Pretreatment with KATP
      selective opener (diazoxide, DZX) significantly inhibited HG-induced mesangial
      cell proliferation, Collagen IV production and decrease in KATP channel activity
      in rat mesangial cells, which were reversed by pretreatment of 5
      hydroxydecanoate, a selective inhibitor of KATP. Moreover, AICAR pretreatment
      inhibited HG-induced decrease in KATP channel activity. CONCLUSIONS: Taken
      together, activating AMPK-KATP signaling may protect against HG-induced mesangial
      cell proliferation and Collagen IV production, and, thereby, provides new
      insights into the molecular mechanisms underlying early diabetic nephropathy
      (DN).

PMID- 28748495
TI  - Evidence for interactions between homocysteine and genistein: insights into
      stroke risk and potential treatment.
AB  - Elevated plasma homocysteine (2-amino-4-sulfanylbutanoic acid) level is a risk
      factor for stroke. Moreover, it has been suggested that high levels of
      homocysteine in the acute phase of an ischemic stroke can predict mortality,
      especially in stroke patients with the large-vessel atherosclerosis subtype. In
      clinical studies, supplementation with genistein (5, 7-dihydroxy-3- (4
      hydroxyphenyl)-4H-1-benzopyran-4-one) decreased plasma homocysteine levels
      considerably. Therefore, genistein could be considered as a potential drug for
      prevention and/or treatment of stroke. However, the mechanism of the effect of
      genistein on homocysteine level remains to be elucidated. In this report, direct
      functional interactions between homocysteine and genistein are demonstrated in in
      vitro experimental systems for determination of methylenetetrahydrofolate
      reductase (MetF) and glutathione peroxidase (GPx) activities, reconstructed with
      purified compounds, and in a simple in vivo system, based on measurement of
      growth rate of Vibrio harveyi and Bacillus subtilis cultures. Results of
      molecular modelling indicated that homocysteine can directly interact with
      genistein. Therefore, genistein-mediated decrease in plasma levels of
      homocysteine, and alleviation of biochemical and physiological effects of one of
      these compounds by another, might be ascribed to formation of homocysteine
      genistein complexes in which biological activities of these molecules are
      abolished or alleviated.

PMID- 28748496
TI  - Huperzine A alleviates neuroinflammation, oxidative stress and improves cognitive
      function after repetitive traumatic brain injury.
AB  - Traumatic brain injury (TBI) may trigger secondary injury cascades including
      endoplasmic reticulum stress, oxidative stress, and neuroinflammation.
      Unfortunately, there are no effective treatments targeting either primary or
      secondary injuries that result in long-term detrimental consequences. Huperzine A
      (HupA) is a potent acetylcholinesterase inhibitor (AChEI) that has been used
      treatment of Alzheimer's disease (AD). This study aimed to explore the
      neuroprotective effects of HupA in TBI and its possible mechanisms. Repetitive
      mild closed head injury (CHI) model was used to mimic concussive TBI. Mice were
      randomly assigned into three groups including sham, vehicle-treated and HupA
      treated injured mice. The HupA was given at dose of 1.0 mg/kg/day and was
      initiated 30 min after the first injury, then administered daily for a total of
      30 days. The neuronal functions including motor functions, emotion-like
      behaviors, learning and memory were tested. Axonal injury, reactive oxygen
      species (ROS), and neuroinflammation were examined as well. The results showed
      that injured mice treated with HupA had significant improvement in Morris water
      maze performance compared with vehicle-treated injured mice. HupA treatment
      significantly attenuated markers of neuroinflammation and oxidative stress in the
      injured mice. Taken together, HupA was effective in reducing neuroinflammation,
      oxidative stress and behavioral recovery after TBI. HupA is a promising candidate
      for treatment of TBI.

PMID- 28748497
TI  - A large-scale study on the effects of sex on gray matter asymmetry.
AB  - Research on sex-related brain asymmetries has not yielded consistent results.
      Despite its importance to further understanding of normal brain development and
      mental disorders, the field remains relatively unexplored. Here we employ a
      recently developed asymmetry measure, based on the Dice coefficient, to detect
      sex-related gray matter asymmetries in a sample of 457 healthy participants (266
      men and 191 women) obtained from 5 independent databases. Results show that
      women's brains are more globally symmetric than men's (p < 0.001). Although the
      new measure accounts for asymmetries distributed all over the brain, several
      specific structures were identified as systematically more symmetric in women,
      such as the thalamus and the cerebellum, among other structures, some of which
      are typically involved in language production. These sex-related asymmetry
      differences may be defined at the neurodevelopmental stage and could be
      associated with functional and cognitive sex differences, as well as with
      proneness to develop a mental disorder.

PMID- 28748498
TI  - The value of explicitly emulating a target trial when using real world evidence:
      an application to colorectal cancer screening.
AB  - Observational analyses for causal inference often rely on real world data
      collected for purposes other than research. A frequent goal of these
      observational analyses is to use the data to emulate a hypothetical randomized
      experiment, i.e., the target trial, that mimics the design features of a true
      experiment, including a clear definition of time zero with synchronization of
      treatment assignment and determination of eligibility. We review a recent
      observational analysis that explicitly emulated a target trial of screening
      colonoscopy using insurance claims from U.S. Medicare. We then compare this
      explicit emulation with alternative, simpler observational analyses that do not
      synchronize treatment assignment and eligibility determination at time zero
      and/or do not allow for repeated eligibility. This empirical comparison suggests
      that lack of an explicit emulation of the target trial leads to biased estimates,
      and shows that allowing for repeated eligibility increases the statistical
      efficiency of the estimates.

PMID- 28748500
TI  - Digital droplet PCR (ddPCR) for the detection and quantification of HPV 16, 18,
      33 and 45 - a short report.
AB  - PURPOSE: Human papilloma virus (HPV) infection is associated with several
      anogenital malignancies. Here, we set out to evaluate digital droplet PCR (ddPCR)
      as a tool for HPV 16, 18, 33 and 45 viral load quantification and, in addition,
      to compare the efficacy of the ddPCR assay for HPV 16 detection with that of
      quantitative real-time PCR (qPCR). METHODS: Clinical samples, positive for HPV
      genotypes 16, 18, 33 and 45 were analyzed for viral load using ddPCR. Sample DNA
      was cleaved before droplet generation and PCR. Droplets positive for VIC and FAM
      fluorescence were read in a QX200 Droplet readerTM (BIO-RAD) after which the
      viral load was calculated using Quantasoft software. RESULTS: We found that DNAs
      extracted from formalin fixed paraffin embedded (FFPE) tissue samples yielded
      lower amplification signals compared to those obtained from liquid based cytology
      (LBC) samples, but they were clearly distinguishable from negative background
      signals. The viral limit of detection was 1.6 copies of HPV 16, 2.8 copies of HPV
      18, 4.6 copies of HPV 33 and 1.6 copies of HPV 45. The mean inter-assay
      coefficients of variability (CV) for the assays ranged from 3.4 to 7.0%, and the
      mean intra-assay CV from 2.6 to 8.2%. The viral load in the different cohorts of
      tumor samples ranged from 154 to 340,200 copies for HPV 16, 244 to 31,300 copies
      for HPV 18 and 738 to 69,100 copies for HPV 33. One sample positive for HPV 45
      contained 1331 viral copies. When comparing qPCR data with ddPCR copy number
      data, the qPCR values were found to be 1 to 31 times higher. CONCLUSIONS:
      Separation of fragments in nanodroplets may facilitate the amplification of
      fragmented human and viral DNA. The method of digital droplet PCR may, thus,
      provide a new and promising tool for evaluating the HPV viral load in clinical
      samples.

PMID- 28748502
TI  - Case report: Robot-assisted laparoscopic excision of giant ganglioneuroma of the
      adrenal gland.

PMID- 28748503
TI  - Role of 18F-FDG PET/CT in patients affected by Langerhans cell histiocytosis.
AB  - PURPOSE: Langerhans cell histiocytosis (LCH) is a rare hematological disorder for
      which the utility of18F-FDG PET/CT is unclear. Our aim was to explore the
      metabolic features of LCH and the possible role of18F-FDG PET/CT in LCH
      evaluation. MATERIALS AND METHODS: We found 17 patients with histologically
      proven LCH who underwent 1718F-FDG PET/CT scans for staging and 42 scans for
      restaging/follow-up purposes. PET/CT results were compared with those obtained
      from other conventional imaging modalities (bone scintigraphy, plain radiogram,
      computed tomography, magnetic resonance). RESULTS: 18F-FDG PET/CT was positive in
      15/17 patients, and it detected 36/37 lesions; all bone and extraskeletal
      lesions, except for a cecal lesion, were18F-FDG-avid. Only 1/4 of the patients
      with lung LCH had hypermetabolic lesions. The average SUVmax of the FDG-avid
      lesions was 7.3 +/- 6.7, the average lesion-to-liver SUVmax ratio was 3.4 +/-
      2.5, and the average lesion-to-blood pool SUVmax ratio was 4 +/- 3.2. In
      comparison to other imaging methods,18F-FDG PET/CT detected additional lesions or
      was able to evaluate treatment response earlier in 33/74 cases; it was
      confirmatory in 38/74 and detected fewer lesions in 3/74 (all three with lung
      LCH). CONCLUSIONS: 18F-FDG PET/CT seems to be useful for evaluating LCH when
      compared to conventional imaging, except in pulmonary cases. It can be used both
      for staging and restaging purposes.

PMID- 28748504
TI  - Whole brain analyses of age-related microstructural changes quantified using
      different diffusional magnetic resonance imaging methods.
AB  - PURPOSE: The new diffusional magnetic resonance imaging (dMRI) techniques,
      diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density
      imaging (NODDI) have been developed to clarify the microstructural changes. To
      our knowledge, however, there is little information on the similarities and
      differences of these metrics evaluated by the image-by-image paired t test.
      MATERIALS AND METHODS: Twenty-three healthy subjects underwent dMRI. We estimated
      the relationships of these metrics evaluated by the image-by-image paired t-test
      and compared aging effects on each metric. RESULTS: We found that fractional
      anisotropy (FA), mean kurtosis (MK) derived from DKI and neurite density index
      (NDI) values derived from NODDI correlated with each other positively, and mean
      diffusivity (MD) and orientation dispersion index (ODI) values from NODDI
      correlated negatively with the FA value. There were no significant relationships
      of age with FA or MD values, while MK, ODI and NDI values showed significant
      correlations with age. CONCLUSION: These results may indicate not only the
      similar tendency among the metrics, but also the higher sensitivity of NODDI and
      DKI to the changes in microstructural tissue organization with advancing age.
      These techniques could shed light on both normal and degenerated brain changes.

PMID- 28748505
TI  - Comparison of Consecutive Results from Fine Needle Aspiration and Core Needle
      Biopsy in Thyroid Nodules.
AB  - There are papers suggesting the complementary role of core needle biopsy (CNB) in
      the diagnosis of thyroid nodules. By comparing the result of CNB and fine needle
      aspiration (FNA) cytology performed in consecutive cases of thyroid nodules, the
      role of CNB was evaluated. Retrospective reviews of 2131 FNA and 275 CNB which
      were performed as first-line biopsy for 2406 thyroid nodules in 2187 patients
      were performed. The ultrasound (US) feature of thyroid nodule was classified
      following the risk of malignancy suggested by American Thyroid Association (ATA)
      guideline. Rate of unsatisfactory and cellular atypia could be decreased
      significantly by first-line CNB in all US group, and the nodules with highly
      suspicious feature showed significant decrease in inconclusive result by first
      line CNB. However, increased rates of architectural and follicular neoplasm (FN)
      were identified in CNB group especially in intermediate and low suspicious
      nodules, and the first-line CNB could not decrease the inconclusive result in
      these US groups. The diagnostic rate of neoplasm diagnosed by surgery following
      the result of architectural atypia or FN was not different between FNA and CNB
      even with significantly higher rate in CNB group. Furthermore, the sensitivity
      for follicular neoplasm (21.2 vs. 61.9%) was significantly higher in CNB group.
      The CNB can be considered in nodules with highly suspicious feature with
      advantage of significantly lower inconclusive diagnostic rate than FNA group.
      However, significantly increased diagnosis of architectural atypia or FN in other
      nodules by CNB is recognized and should be evaluated in future to understand the
      meaning.

PMID- 28748501
TI  - A step-by-step microRNA guide to cancer development and metastasis.
AB  - BACKGROUND: Cancer is one of the leading causes of mortality. The neoplastic
      transformation of normal cells to cancer cells is caused by a progressive
      accumulation of genetic and epigenetic alterations in oncogenes, tumor suppressor
      genes and epigenetic regulators, providing cells with new properties,
      collectively known as the hallmarks of cancer. During the process of neoplastic
      transformation cells progressively acquire novel characteristics such as
      unlimited growth potential, increased motility and the ability to migrate and
      invade adjacent tissues, the ability to spread from the tumor of origin to
      distant sites, and increased resistance to various types of stresses, mostly
      attributed to the activation of genetic stress-response programs. Accumulating
      evidence indicates a crucial role of microRNAs (miRNAs or miRs) in the initiation
      and progression of cancer, acting either as oncogenes (oncomirs) or as tumor
      suppressors via several molecular mechanisms. MiRNAs comprise a class of small
      ~22 bp long noncoding RNAs that play a key role in the regulation of gene
      expression at the post-transcriptional level, acting as negative regulators of
      mRNA translation and/or stability. MiRNAs are involved in the regulation of a
      variety of biological processes including cell cycle progression, DNA damage
      responses and apoptosis, epithelial-to-mesenchymal cell transitions, cell
      motility and stemness through complex and interactive transcription factor-miRNA
      regulatory networks. CONCLUSIONS: The impact and the dynamic potential of miRNAs
      with oncogenic or tumor suppressor properties in each stage of the multistep
      process of tumorigenesis, and in the adaptation of cancer cells to stress, are
      discussed. We propose that the balance between oncogenic versus tumor suppressive
      miRNAs acting within transcription factor-miRNA regulatory networks, influences
      both the multistage process of neoplastic transformation, whereby normal cells
      become cancerous, and their stress responses. The role of specific tumor-derived
      exosomes containing miRNAs and their use as biomarkers in diagnosis and
      prognosis, and as therapeutic targets, are also discussed.

PMID- 28748506
TI  - Impact of Awareness Programs on Cholera Dynamics: Two Modeling Approaches.
AB  - We propose two differential equation-based models to investigate the impact of
      awareness programs on cholera dynamics. The first model represents the disease
      transmission rates as decreasing functions of the number of awareness programs,
      whereas the second model divides the susceptible individuals into two distinct
      classes depending on their awareness/unawareness of the risk of infection. We
      study the essential dynamical properties of each model, using both analytical and
      numerical approaches. We find that the two models, though closely related,
      exhibit significantly different dynamical behaviors. Namely, the first model
      follows regular threshold dynamics while rich dynamical behaviors such as
      backward bifurcation may arise from the second one. Our results highlight the
      importance of validating key modeling assumptions in the development and
      selection of mathematical models toward practical application.

PMID- 28748507
TI  - Intergenerational Neighborhood Attainment and the Legacy of Racial Residential
      Segregation: A Causal Mediation Analysis.
AB  - Advances in mediation analysis are used to examine the legacy effects of racial
      residential segregation in the United States on neighborhood attainments across
      two familial generations. The legacy effects of segregation are anticipated to
      operate through two primary pathways: a neighborhood effects pathway and an urban
      continuity pathway. The neighborhood effects pathway explains why parent's
      exposure to racial residential segregation during their family-rearing years can
      influence the residential outcomes of their children later in life. The urban
      continuity pathway captures the temporal consistency of the built and
      topographical environment in providing similar residential opportunities across
      generations. Findings from the Panel Study of Income Dynamics and U.S. Census
      data indicate that the legacy effect of racial residential segregation among
      black families operates primarily through the neighborhood effects that influence
      children growing up. For white families, there is less support for the legacy
      effects of segregation. The findings are supported by a comprehensive mediation
      analysis that provides a formal sensitivity analysis, deploys an instrumental
      variable, and assesses effect heterogeneity. Knowledge of the legacy of
      segregation moves neighborhood attainment research beyond point-in-time studies
      of racial residential segregation to provide a deeper understanding into the ways
      stratified residential environments are reproduced.

PMID- 28748508
TI  - Autophagy enhancement is rendered ineffective in presence of alpha-synuclein in
      melanoma cells.
AB  - Increased cellular concentration of alpha-synuclein (alpha-syn) predisposes it to
      misfolding and aggregation that in turn impair the degradation pathways. This
      poses a limitation to the use of overexpression models for studies on alpha-syn
      clearance by autophagy, which is widely investigated for its therapeutic
      potential. This limitation can be overcome with the use of endogenous models. In
      this study, SK-MEL-28, a melanoma cell model with endogenous alpha-syn
      expression, was employed to study alpha-syn clearance through autophagy. We
      demonstrated the dual localization of alpha-syn to nucleus and cytoplasm that
      varied in response to changes in cellular environment. Autophagy inhibition and
      exposure to dopamine favored cytoplasmic localization of alpha-syn, while
      autophagy induction favored increased localization to the nucleus. The inhibitory
      effect of dopamine on autophagy was heightened in presence of alpha-syn.
      Additionally, because alpha-syn had a regulatory effect on autophagy, cells
      showed an increased resistance to autophagy induction in presence of alpha-syn.
      This resistance prevented effective induction of autophagy even under conditions
      of prolonged autophagy inhibition. These results highlight alternate
      physiological roles of alpha-syn, particularly in non-neuronal cells. Because
      autophagy enhancement could reverse neither the increase in alpha-syn levels nor
      the autophagy inhibition, there arises a need to evaluate the efficacy of
      autophagy-based therapeutic strategies.

PMID- 28748509
TI  - Clinical characteristics and thrombosis outcomes of paediatric antiphospholipid
      syndrome: analysis of 58 patients.
AB  - The study aims to analyse the clinical and immunological manifestations of
      paediatric antiphospholipid syndrome (APS) in patients, based on the 2006 revised
      classification criteria of definite APS. Fifty-eight paediatric patients with APS
      were enrolled and analysed retrospectively. A total of 37 female and 21 male
      patients with a mean age of 14 +/- 3 years at disease onset were included.
      Fourteen (24%) cases were primary APS, and 40 (69%) cases were secondary to
      systemic lupus erythaematosus (SLE). Anti-nuclear antibody (ANA) positivity and
      hypocomplementemia were more common in secondary APS than in primary APS. The
      most common manifestations of thrombosis were deep vein thrombosis of the lower
      extremities (25 cases, 37%). Non-thrombotic manifestations were mainly
      immunologic thrombocytopenia, autoimmune haemolytic anaemia, skin lesions,
      arthritis, pulmonary hypertension, heart valve vegetations and spontaneous
      abortion. LA, ACL and anti-beta2GPI were positive in 42 (95%), 28 (64%) and 34
      (77%) cases, respectively. Over half (23 cases, 52%) of the patients were triple
      positive for antiphospholipid (aPL) antibodies. Among patients with single
      positive LA and anti-beta2GPI, the proportion with venous thrombosis was 100% (5
      cases) and 0% (0 cases), respectively. The arterial thrombosis proportions were
      22% (5 cases), 21% (3 cases) and 14% (1 case) in the triple-, double- and single
      aPL-positive groups, respectively (P > 0.05). Fifty-three (91%) cases were
      followed up for 3 to 140 months, with a median time of 32 months. Seven (13%)
      cases had recurrences or appearances of thrombosis during follow-up, all of which
      were double- or triple-aPL positive. APS in the paediatric patients is mostly
      secondary to SLE. ANA positivity and hypocomplementemia are more common in
      secondary APS, but there are no differences in the other clinical manifestations
      between the primary and secondary APS groups. Deep vein thrombosis is the most
      common thrombotic event. Positive LA may increase the risk of venous thrombosis.
      Multiple-aPL positivity does not increase the proportion of thrombosis. Long-term
      anticoagulant or antiplatelet therapy is needed to prevent thrombosis recurrence
      in double- or triple-positive aPL cases.

PMID- 28748510
TI  - Clinical characteristics of autoimmune rheumatic disease-related organizing
      pneumonia.
AB  - To study the clinical characteristics of autoimmune rheumatic disease-related
      organizing pneumonia (AIRD-OP), the clinical presentation, radiological findings,
      treatment, and outcome of AIRD-OP patients were analyzed, in comparison with
      patients with cryptogenic organizing pneumonia (COP). A total of 131 OP patients
      were identified, including 57 cases of AIRD-OP, 35 cases of COP, and 39 cases of
      other disease-related OPs. Among AIRD-OP patients, 36 (63%) presented the
      symptoms of OP at onset. The primary disease of AIRDs included Sjogren's syndrome
      (38%), polymyositis/dermatomyositis (23%), rheumatoid arthritis (23%), and
      undifferentiated AIRD. Compared with COP patients, the prevalence of patients
      having cough and malaise at baseline was significantly lower (54.4 vs 82.9%, P <
      0.05; 49.1 vs 70.6%, P < 0.05), and the signs of moist rales and crackles were
      more common in AIRD-OP patients (54.4 vs 32.4%, P < 0.05; 49.1 vs 26.5%, P <
      0.05). Lung function (TLC%, FVC%) was more significantly reduced in AIRD-OP
      patients (72 vs 97%, P < 0.05;75 vs 96%, P < 0.05). The dosage of corticosteroids
      prescribed was significantly higher in AIRD-OP patients (44 vs 37 mg/day, P <
      0.05). The complete recovery rate was slightly lower in AIRD-OP patients (22.2 vs
      29%, P > 0.05) with a tendency towards higher recurrence rate in AIRD-OP patients
      (32.7 vs 14.3%, P < 0.05). AIRD-OP may be the most common cause of OP. OP can be
      the initial presentation of AIRD. Compared with COP patients, AIRD-OP patients
      are characterized with occult onset but more severe lung involvement and higher
      recurrence rate.

PMID- 28748511
TI  - Unique histologic features of tonsils from patients with periodic fever, aphthous
      stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.
AB  - The objective of this study is to compare the histology and immune cell
      composition of tonsils from patients with periodic fever, aphthous stomatitis,
      pharyngitis, and cervical adenitis (PFAPA) syndrome to those from patients with
      obstructive sleep apnea (OSA). Patients with PFAPA and age-matched controls with
      OSA who had undergone tonsillectomy at Vanderbilt Children's Hospital were
      recruited. After informed consent, archival paraffin-embedded, formalin-fixed
      tonsil tissues were obtained. Sizes of major histologic regions were measured.
      Cores of germinal centers, crypts, and squamous epithelium were assembled on a
      tissue microarray for immunohistochemical staining and digital image analysis.
      Features of tonsils from PFAPA and OSA patients were compared with Wilcoxon
      signed-rank test. Samples from 16 cases with PFAPA and 16 controls with OSA were
      evaluated. Tonsils from PFAPA cases had significantly smaller germinal centers
      (0.18 vs. 0.47 mm2, p = 0.001) and wider squamous epithelia (176 vs. 138 MUm, p =
      0.008) than those of OSA patients. The percentages of B and T lymphocytes and
      myeloid cells were comparable in germinal centers, crypts, and squamous epithelia
      from PFAPA and OSA patients. Longer time from the last febrile episode in PFAPA
      cases was associated with larger germinal center area (Spearman's rho = 0.61, p =
      0.02). We found differences in the sizes of germinal centers and squamous
      epithelia in tonsils of patients with PFAPA and OSA, but the cellular
      compositions within these areas were comparable. Our results suggest that tonsils
      from patients with PFAPA change histologically over time with enlarging germinal
      centers following a febrile episode. Additional studies are needed to understand
      the pathogenesis of PFAPA.

PMID- 28748512
TI  - Cross-cultural adaptation and validation of the Chinese version of the Health
      Assessment Questionnaire for the Spondyloarthropathies (HAQ-S).
AB  - The Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) is a
      commonly used questionnaire to evaluate function and health status of patients
      with ankylosing spondylitis (AS). The objective of this study was to cross
      culturally adapt the HAQ-S into Chinese and then to evaluate its reliability and
      validity. The Chinese version of the HAQ-S was obtained with a five-step
      procedure of translation and cross-cultural adaptation. All invited patients met
      the New York criteria for AS, and a total of 103 patients finally participated in
      this study. Intraclass correlation coefficient (ICC) was used to evaluate the
      test-retest and inter-rater reliability of the HAQ-S. Internal consistency of the
      questionnaire was evaluated by Cronbach's alpha coefficient. Spearman's
      correlation coefficient was calculated to assess the construct validity between
      the HAQ-S and Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index
      (BASFI), Bath AS Metrology Index (BASMI), and the laboratory parameters
      (erythrocyte sedimentation rate, ESR; C-reactive protein, CRP). Test-retest and
      inter-rater reliability were excellent with intraclass correlation coefficients
      of 0.987 (p < 0.05) and 0.982 (p < 0.05), respectively. The overall internal
      consistency of the HAQ-S was found satisfactory (Cronbach's alpha = 0.914). The
      Chinese version of the HAQ-S correlated good with the BASFI (r = 0.749, p <
      0.01), and moderate with the BASDAI (r = 0.581, p < 0.01) and the BASMI (r =
      0.425, p < 0.01). But, the adapted questionnaire correlated poorly with ESR (r =
      0.298, p < 0.01) or CRP (r = 0.283, p < 0.01). The Chinese version of the HAQ-S
      is reliable and valid for the evaluation of Chinese-speaking patients with AS.

PMID- 28748513
TI  - Africa Journal of Rheumatology: enhancing the visibility of rheumatology in
      Africa.

PMID- 28748514
TI  - A systemic review and meta-analysis of the clinical efficacy and safety of total
      glucosides of peony combined with methotrexate in rheumatoid arthritis.
AB  - To assess the efficacy and safety of the combination of total glucoside of peony
      (TGP) and methotrexate (MTX) for the treatment of rheumatoid arthritis (RA).
      Randomized controlled trial (RCT) data on the traditional Chinese active
      component TGP combined with MTX vs. MTX alone for the treatment of RA was
      collected by searching the Pubmed, Embase, Cochrane Library, CNKI, VIP Journals
      database, and Wanfang database up to February 2017. Study selection, data
      extraction, data synthesis, and data analyses were performed according to the
      Cochrane standards. A total of eight RCTs involving 522 participants were
      included in this meta-analysis. Compared with MTX alone, the use of TGP combined
      with MTX exhibited better therapeutic effects for the treatment of RA (P =
      0.004). In addition, TGP combined with MTX caused a more significant decrease in
      erythrocyte sedimentation rate (ESR) (P < 0.0001) and swollen joint count (SJC)
      (P < 0.00001). However, no significant differences were found in C-reactive
      protein (CRP) (P = 0.19), duration of morning stiffness (DMS) (P = 0.32), or
      tender joint count (TJC) (P = 0.23) between the two groups. In addition, adverse
      events were more frequently reported in the MTX monotherapy group than in the TGP
      and MTX combination group (P = 0.0007). Our study demonstrates that TGP combined
      with MTX is more effective than MTX alone for the treatment of RA. Nevertheless,
      the adverse effects of the combination of TGP and MTX need to be further
      assessed. Due to the poor methodological quality of included trials, well
      designed, multi-center, and large-scale RCTs are necessary to draw a more
      definitive conclusion.

PMID- 28748515
TI  - Tumor necrosis factor-alpha -308 polymorphism in North Indian rheumatoid
      arthritis patients and association with mRNA and serum TNF-alpha.
AB  - Rheumatoid arthritis (RA) is a severely disabling chronic autoimmune disorder
      that leads to progressive inflammation of the joints and surrounding tissues. TNF
      alpha, a potent proinflammatory cytokine, plays a pivotal role in the
      pathogenesis of RA. The endogenous formation of TNF-alpha may be influenced by
      TNF-alpha promoter polymorphisms. Hence, the present study was designed to
      explore any possible association between genetic polymorphism of TNF-alpha -308
      G/A, messenger RNA (mRNA) expression, serum levels of TNF-alpha, and inflammatory
      markers in North Indian RA patients. A total of 214 controls and 187 RA patients
      were recruited according to the revised American College of Rheumatology 2010
      criteria. TNF-alpha -308 G/A genetic polymorphism within promoter region was
      analyzed by using PCR-RFLP. Levels of inflammatory markers and serum TNF-alpha
      were estimated by ELISA. The mRNA expression of TNF-alpha gene was measured by
      quantitative real-time PCR. Higher levels of autoantibodies (RF and anti-CCP)
      were present in RA patients as compared to controls. We found a positive and
      significant correlation of circulating TNF-alpha levels with RF (r = 0.18), anti
      CCP (r = 0.16), and mRNA expression of TNF-alpha gene (r = 0.57) in RA patients.
      The mRNA expression levels of TNF-alpha was 4.5-fold higher in patients with RA
      as compared to controls. The heterozygous mutant variants (G/A) and homozygous
      mutant variants (A/A) were found to be significantly associated with RA as
      compared to control (OR = 1.52 and 3.02, respectively). Our observations
      illustrated a significant association of allele -308 A TNF-alpha with progression
      of RA. Significant and positive correlation of TNF-alpha levels with mRNA
      expression and inflammatory marker levels suggests that serum TNF-alpha may be a
      susceptibility marker for RA.

PMID- 28748516
TI  - Colorimetric Sensing of Toxic Metal and Antibacterial Studies by Using Bioextract
      Synthesized Silver Nanoparticles.
AB  - Here, we report the simple and cost effective colorimetric technique for the
      determination of toxic metals (Hg2+) in aqueous sample by using bioextract silver
      nanoparticles (AgNPs). The indigenous AgNPs were synthesised by green and
      ecologically friendly style using extract of fig (Ficus carica) leaf. The
      synthesized AgNPs were confirmed by UV-vis spectroscopy, FT-IR spectroscopy, and
      scanning electron microscopy methods. The synthesis of AgNPs was observed by its
      colour changing from light yellow to dark brownish. The existence of
      furanocoumarins bioactive materials in the fig leaf extract, which act as bio
      reducing and capping agent, help in the formation of stabilized silver
      nanoparticles. In addition, the bacterial activity of the synthesized silver
      nanoparticles was tested against gram-negative (Klebsiella oxytocam, Pseudomonas
      aeruginosam, Shigella flexneri and Proteus mirabilis), gram-positive
      (Staphylococcus aureus and Micrococcus luteus) and one Candida (Candida albicans)
      human pathogen and the results showed moderate activity.

PMID- 28748517
TI  - Analysis of Cation-Dependent DNA (G3T1)4 Shape Change Using Fluorescence
      Correlation Spectroscopy.
AB  - In G-rich DNA, it is well known that the form changes from single-strand DNA to G
      quadruplex due to cations. In this study, we analyze the diffusion coefficient
      and fluorescence intensity obtained by fluorescence correlation spectroscopy for
      short G-rich DNA of the (G3T1)4 sequence labeled as 5-Carboxytetramethylrhodamine
      (TAMRA) with variation of the K+ ion concentration. At a K+ ion concentration of
      more than 200 mM, the single-strand DNA was changed to the G-quadruplex. The size
      of the G-quadruplex decreased to 86% than the size of the single strand DNA at K+
      ion concentration of 0 M. The size of the G-quadruplex and the fluorescence
      intensity of TAMRA attached to the DNA were constant with an increase in the K+
      ion concentration between 200 and 800 mM. This means that the size of the DNA and
      the fluorescence intensity of the TAMRA are not affected by the K+ ion
      concentration at the G-quadruplex structure because the binding structure of DNA
      and TAMRA dye leads to stability at a concentration of less than 100 mM K+. Based
      on our short G-rich DNA results, longer G-rich DNA is analyzed for the diffusion
      coefficient of the DNA and the fluorescence intensity variation of fluorescence
      dye attached to the DNA.

PMID- 28748518
TI  - Species Richness and Abundance of Cerambycidae (Coleoptera) in Huatulco, Oaxaca,
      Mexico; Relationships with Phenological Changes in the Tropical Dry Forest.
AB  - Cerambycidae have an important ecological role in initiating the degradation
      process of dead wood, but few studies have evaluated Cerambycidae community
      attributes in relation to ecosystem phenology. We surveyed the cerambicid fauna
      of the tropical dry forest in Huatulco, Oaxaca, Mexico, and explored the
      relationship of Cerambycidae species richness and abundance with phenological
      changes in vegetation. We applied three collecting methods of light traps, direct
      collection, and Malaise traps to survey Cerambycidae throughout 2005. To
      determine seasonal variations, we collected samples in the dry season month of
      February in the rainy season of May-July and August-September, and in the
      transition months of October and November through. We collected and identified
      145 species, 88 genera, 37 tribes, and four subfamilies. The subfamily with the
      highest number of species was Cerambycinae (100 species), and the tribe with the
      highest number of genera and species was Elaphidiini with 13 genera and 33
      species. The ICE non-parametric estimator determined an overall expected richness
      of 373 species, while the overall Shannon Diversity Index was 4.1. Both species
      richness and abundance varied seasonally, with the highest values recorded in the
      rainy season and the lowest in the dry season. Overall species abundance was not
      significantly correlated to monthly rainfall or EVI neither, only for "direct
      collecting" the EVI vs Richness and EVI vs Shannon Diversity Index were
      significantly correlated. We propose that the seemingly contradictory
      relationships between seasonal richness patterns of Cerambycidae and the
      greening/senescence of vegetation (EVI) may be explained by the seasonal
      availability of dead organic matter, flowers, or leafy vegetation that may be
      synchronized with the behavior of different cerambycid species.

PMID- 28748519
TI  - Obstetric antiphospholipid syndrome and long term arterial thrombosis risk.
AB  - Antiphospholipid syndrome (APS) is classified as the association of a thrombotic
      event and/or obstetric morbidity in patients persistently positive for
      antiphospholipid antibodies and/or lupus anticoagulant. To evaluate the incidence
      of subsequent thrombosis among women diagnosed with purely obstetric APS. We
      retrospectively reviewed and collected demographic and clinical data from the
      computerized charts of all patients with obstetric APS, from 1992 to 2017.
      Eligibility criteria included all women diagnosed with APS, according to the 2006
      revised criteria, for whom the clinical manifestations were purely obstetric. The
      primary endpoint was the occurrence of subsequent thromboembolic events,
      following diagnosis of obstetric APS. The study included 115 women diagnosed with
      obstetric APS. During the study's follow up period, 12 (10.4%) women developed
      thrombosis. Of the 12 women who developed thrombosis, 9 (75%) of the thrombotic
      events were arterial. The site of arterial thrombosis was cerebral in all cases.
      Venous thrombosis occurred in 3 (25%) women, including one in each of the
      following sites-pulmonary embolism, ovarian vein thrombosis and proximal leg deep
      vein thrombosis. Our data suggests that women with obstetric APS are at risk for
      subsequent long-term thrombosis, especially arterial cerebral events. We did not
      identify any clinical or laboratory unique features among women with obstetric
      APS who will eventually develop thrombosis.

PMID- 28748520
TI  - Advances in the development of improved animal-free models for use in breast
      cancer biomedical research.
AB  - Through translational research, the outcomes for women (and men) diagnosed with
      breast cancer have improved significantly, with now over 80% of women surviving
      for at least 5 years post-diagnosis. Much of this success has been translated
      from the bench to the bedside using laboratory models. Here, we outline the types
      of laboratory models that have helped achieve this and discuss new approaches as
      we move towards animal-free disease modelling.

PMID- 28748521
TI  - Clinical outcome of alveolar ridge augmentation with individualized CAD-CAM
      produced titanium mesh.
AB  - BACKGROUND: The augmentation of the jaw has been and continues to be a
      sophisticated therapy in implantology. Modern CAD-CAM technologies lead to
      revival of old and established augmentation techniques such as the use of
      titanium mesh (TM) for bone augmentation. The aim of this retrospective study was
      to evaluate the clinical outcome of an individualized CAD-CAM-produced TM based
      on the CT/DVT-DICOM data of the patients for the first time. METHODS: In 17
      patients, 21 different regions were augmented with an individualized CAD-CAM
      produced TM (Yxoss CBR(r), Filderstadt, Germany). For the augmentation, a mixture
      of autologous bone and deproteinized bovine bone mineral (DBBM) or autologous
      bone alone was used. Reentry with explantation of the TM and simultaneous
      implantation of 44 implants were performed after 6 months. Preoperative and 6
      month postoperative cone beam computed tomographies (CBCT) were performed to
      measure the gained bone height. RESULTS: The success rate for the bone grafting
      procedure was 100%. Thirty-three percent of cases presented an exposure of the TM
      during the healing period. However, premature removal of these exposed meshes was
      not necessary. Exposure rate in augmentations performed with mid-crestal
      incisions was higher than in augmentations performed with a modified poncho
      incision (45.5 vs. 20%, p = 0.221). In addition, exposure rates in the maxilla
      were significantly higher than in the mandible (66.7 vs. 8.3%, p = 0.009).
      Gender, smoking, periodontal disease, gingiva type, used augmentation material,
      and used membrane had no significant influence on the exposure rate (p > 0.05).
      The mean vertical augmentation was 6.5 +/- 1.7 mm, and the mean horizontal
      augmentation was 5.5 +/- 1.9 mm. Implant survival rate after a mean follow-up of
      12 +/- 6 months after reentry was 100%. CONCLUSION: Within the limits of the
      retrospective character of this study, this study shows for the first time that
      individualized CAD-CAM TM provide a sufficient and safe augmentation technique,
      especially for vertical and combined defects. However, the soft tissue handling
      for sufficient mesh covering remains one of the most critical steps using this
      technique.

PMID- 28748522
TI  - Mindfulness-Based Interventions and Sleep Among Cancer Survivors: a Critical
      Analysis of Randomized Controlled Trials.
AB  - PURPOSE OF REVIEW: The purpose of our critical examination is to present results
      and provide a synthesis of this body of work. RECENT FINDINGS: Sleep problems
      among cancer survivors are gaining research attention. To our knowledge, there
      have been six randomized control trials published from 2013 to 2015 that test the
      effects of mindfulness-based interventions (MBIs) on sleep as a primary or
      secondary outcome. Our examination of the literature highlights important
      methodological issues and variability among trials. We conclude our review by
      offering solutions to facilitate more scientific rigor in future studies.

PMID- 28748524
TI  - The effects of segmentation algorithms on the measurement of 18F-FDG PET texture
      parameters in non-small cell lung cancer.
AB  - BACKGROUND: Measures of tumour heterogeneity derived from 18-fluoro-2
      deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)
      scans are increasingly reported as potential biomarkers of non-small cell lung
      cancer (NSCLC) for classification and prognostication. Several segmentation
      algorithms have been used to delineate tumours, but their effects on the
      reproducibility and predictive and prognostic capability of derived parameters
      have not been evaluated. The purpose of our study was to retrospectively compare
      various segmentation algorithms in terms of inter-observer reproducibility and
      prognostic capability of texture parameters derived from non-small cell lung
      cancer (NSCLC) 18F-FDG PET/CT images. Fifty three NSCLC patients (mean age 65.8
      years; 31 males) underwent pre-chemoradiotherapy 18F-FDG PET/CT scans. Three
      readers segmented tumours using freehand (FH), 40% of maximum intensity threshold
      (40P), and fuzzy locally adaptive Bayesian (FLAB) algorithms. Intraclass
      correlation coefficient (ICC) was used to measure the inter-observer variability
      of the texture features derived by the three segmentation algorithms. Univariate
      cox regression was used on 12 commonly reported texture features to predict
      overall survival (OS) for each segmentation algorithm. Model quality was compared
      across segmentation algorithms using Akaike information criterion (AIC). RESULTS:
      40P was the most reproducible algorithm (median ICC 0.9; interquartile range
      [IQR] 0.85-0.92) compared with FLAB (median ICC 0.83; IQR 0.77-0.86) and FH
      (median ICC 0.77; IQR 0.7-0.85). On univariate cox regression analysis, 40P found
      2 out of 12 variables, i.e. first-order entropy and grey-level co-occurence
      matrix (GLCM) entropy, to be significantly associated with OS; FH and FLAB found
      1, i.e., first-order entropy. For each tested variable, survival models for all
      three segmentation algorithms were of similar quality, exhibiting comparable AIC
      values with overlapping 95% CIs. CONCLUSIONS: Compared with both FLAB and FH,
      segmentation with 40P yields superior inter-observer reproducibility of texture
      features. Survival models generated by all three segmentation algorithms are of
      at least equivalent utility. Our findings suggest that a segmentation algorithm
      using a 40% of maximum threshold is acceptable for texture analysis of 18F-FDG
      PET in NSCLC.

PMID- 28748523
TI  - Management and Prevention of Saphenous Vein Graft Failure: A Review.
AB  - Coronary artery bypass grafting (CABG) remains a vital treatment for patients
      with multivessel coronary artery disease (CAD), especially diabetics. The long
      term benefit of the internal thoracic artery graft is well established and
      remains the gold standard for revascularization of severe CAD. It is not always
      possible to achieve complete revascularization through arterial grafts,
      necessitating the use of saphenous vein grafts (SVG). Unfortunately, SVGs do not
      have the same longevity, and their failure is associated with significant adverse
      cardiac outcomes and mortality. This paper reviews the pathogenesis of SVG
      failure, highlighting the difference between early, intermediate, and late
      failure. It also addresses the different surgical techniques that affect the
      incidence of SVG failure, as well as the medical and percutaneous prevention and
      treatment options in contemporary practice.

PMID- 28748525
TI  - Topically applied azaphenothiazines inhibit contact sensitivity to oxazolone in
      mice.
AB  - In this work we investigated the efficacy of two topically applied
      azaphenothiazine derivatives, 9-chloro-6-acetylaminobutylquinobenzo[3,2
      b][1,4]thiazine (compound 4) and 6-chloroethylureidoethyldiquino[3,2-b;2';3'
      e][1,4]thiazine (compound 5), in the amelioration of inflammatory symptoms of
      contact sensitivity (CS) to oxazolone in mice, in relation to the commercial
      ointment Protopic(r) (tacrolimus), the reference drug. The compounds were
      administered 24 h following elicitation of CS and, 24 h later, the parameters of
      inflammation, such as ear edema, blood composition, leukocyte level, numbers of
      cells in the draining lymph nodes, histological picture of the inflamed tissue,
      and the morphometric analysis, were analyzed. The study showed that the
      effectiveness of the studied azaphenothiazines applied as a 0.1% ointment was
      comparable to the reference drug regarding suppression of the inflammatory
      process, when all the investigated histological parameters are taken into
      account.

PMID- 28748526
TI  - A craniometric analysis of early modern Romania and Hungary: The roles of
      migration and conversion in shaping European Ottoman population history.
AB  - OBJECTIVES: Debate persists regarding the biological makeup of European Ottoman
      communities settled during the expansion of the Ottoman Empire during the 16th
      and 17th centuries, and the roles of conversion and migration in shaping
      demography and population history. The aim of this study was to perform an
      assessment of the biological affinities of three European Ottoman series based on
      craniometric data. MATERIALS AND METHODS: Craniometric data collected from three
      Ottoman series from Hungary and Romania were compared to European and Anatolian
      comparative series, selected to represent biological affinity representative of
      historically recorded migration and conversion influences. Sex-separated samples
      were analyzed using D2 -matrices, along with principal coordinates and PERMANOVA
      analyses to investigate biological affinities. Discriminant function analysis was
      employed to assign Ottoman individuals to two potential classes: European or
      Anatolian. RESULTS: Affinity analyses show larger than expected biological
      differences between males and females within each of the Ottoman communities.
      Discriminant function analyses show that the majority of Ottoman individuals
      could be classified as either European or Anatolian with a high probability.
      Moreover, location within Europe proved influential, as the Ottomans from a
      location of more geopolitical importance (Budapest) diverged from more hinterland
      communities in terms of biological affinity patterns. DISCUSSION: The results
      suggest that male and female Ottomans may possess distinct population histories,
      with males and females divergent from each other in terms of their biological
      affinities. The Ottoman communities appear diverse in terms of constituting a mix
      of peoples from different biological backgrounds. The greater distances between
      sexes from the same community, and the differences between communities, may be
      evidence that the processes of migration and conversion impacted individual
      people and groups diversely.

PMID- 28748528
TI  - Parenting practices and children's dental caries experience: A structural
      equation modelling approach.
AB  - AIM: To evaluate the direct and mediated associations between parenting practices
      and dental caries experience in Indian school children. METHODS: The target
      population consisted of school children and their parents (N=1539) of Medak
      district in the state of Telangana, India. Parents completed a questionnaire that
      consisted of questions related to socioeconomic status (SES), family structure,
      the number of children, their own oral hygiene behaviour and parenting practices.
      Parenting practices were assessed using a translated version of the short form of
      Parent-Child Relationship Questionnaire (PCRQ) which was found to have two
      factors, power assertion (ie over control and coercion) and positive parenting
      (warmth and positive parent-child interaction). Children completed a
      questionnaire on tooth brushing frequency, dental visiting and sugar consumption
      practices to evaluate their oral hygiene behaviour, and underwent a clinical
      examination for dental caries by a single examiner. Path analysis was used to
      explore the influence of parent-child relationship, SES and other family-level
      variables on dental caries experience of children. RESULTS: Parents' oral hygiene
      behaviour was positively (beta=0.18, P=0.009), and power assertion negatively
      (beta=-0.06, P=0.041) associated with children's oral hygiene behaviours.
      Families reporting higher SES had children with less dental caries experience
      (beta=-0.10, P=0.028) and better oral hygiene behaviour (beta=0.13, P=0.009).
      Power assertion parenting had an indirect association with dental caries
      experience (beta=0.003, P=0.038). CONCLUSIONS: Children had higher dental caries
      experience when they lived in families with lower SES and used more power
      assertion parenting practices.

PMID- 28748527
TI  - The prevalence of DICER1 pathogenic variation in population databases.
AB  - The DICER1 syndrome is associated with a variety of rare benign and malignant
      tumors, including pleuropulmonary blastoma (PPB), cystic nephroma (CN) and
      Sertoli-Leydig cell tumor (SLCT). The prevalence and penetrance of pathogenic
      DICER1 variation in the general population is unknown. We examined three publicly
      available germline whole exome sequence datasets: Exome Aggregation Consortium
      (ExAC), 1,000 Genomes (1,000 G) and the Exome Sequencing Project (ESP). To avoid
      over-estimation of pathogenic DICER1 variation from cancer-associated exomes, we
      excluded The Cancer Genome Atlas (TCGA) variants from ExAC. All datasets were
      annotated with snpEff and ANNOVAR and variants were classified into four
      categories: likely benign (LB), unknown significance (VUS), likely pathogenic
      (LP), or pathogenic (P). The prevalence of DICER1 P/LP variants was 1:870 to
      1:2,529 in ExAC-nonTCGA (53,105 exomes) estimated by metaSVM and REVEL/CADD,
      respectively. A more stringent prevalence calculation considering only loss-of
      function and previously-published pathogenic variants detected in ExAC-nonTCGA,
      yielded a prevalence of 1:10,600. Despite the rarity of most DICER1 syndrome
      tumors, pathogenic DICER1 variation is more common than expected. If confirmed,
      these findings may inform future sequencing-based newborn screening programs for
      PPB, CN and SLCT, in which early detection improves prognosis.

PMID- 28748529
TI  - Dual role of monocyte-derived dendritic cells in Trypanosoma cruzi infection.
AB  - Pathogens can cause inflammation when inoculated into the skin. The vector
      transmitted protozoan parasite Trypanosoma cruzi induces poor cellular
      infiltration and disseminates, causing high mortality in the experimental model.
      Here, we characterized the inflammatory foci at the parasite inoculation site and
      secondary lymphoid organs using a murine model. While no macrophages and few
      neutrophils and monocytes (Mo) were recruited into the skin, T. cruzi infection
      elicited the mobilization of Ly6C+ Mo to draining lymph nodes and spleen. Over
      time, this population became enriched in CD11b+ Ly6C+ CD11c+ MHCII+ CD86+ cells
      resembling inflammatory dendritic cells (DCs). Adoptive transfer of Ly6C+ Mo
      purified from the bone marrow of CD11c-GFP transgenic mice confirmed the
      monocytic origin of Ly6C+ DCs found in the spleen of infected animals. Isolated
      Mo-derived cells not only produced TNF-alpha and nitric oxide, but also IL-10 and
      displayed a poor capacity to induce lymphoproliferation. Ablation of Mo-derived
      cells by 5-fluorouracil confirmed their dual role during infection, limiting the
      parasite load by inducible nitric oxide synthase-related mechanisms and
      negatively affecting the development of anti-parasite T-cell response. This study
      demonstrated that consistent with their antagonistic properties, these cells not
      only control the parasite spreading but also its persistence in the host.

PMID- 28748530
TI  - IL-6 promotes CD4+ T-cell and B-cell activation during Plasmodium infection.
AB  - Humoral immunity develops in the spleen during blood-stage Plasmodium infection.
      This elicits parasite-specific IgM and IgG, which control parasites and protect
      against malaria. Studies in mice have elucidated cells and molecules driving
      humoral immunity to Plasmodium, including CD4+ T cells, B cells, interleukin (IL)
      21 and ICOS. IL-6, a cytokine readily detected in Plasmodium-infected mice and
      humans, is recognized in other systems as a driver of humoral immunity. Here, we
      examined the effect of infection-induced IL-6 on humoral immunity to Plasmodium.
      Using P. chabaudi chabaudi AS (PcAS) infection of wild-type and IL-6-/- mice, we
      found that IL-6 helped to control parasites during primary infection. IL-6
      promoted early production of parasite-specific IgM but not IgG. Notably, splenic
      CD138+ plasmablast development was more dependent on IL-6 than germinal centre
      (GC) B-cell differentiation. IL-6 also promoted ICOS expression by CD4+ T cells,
      as well as their localization close to splenic B cells, but was not required for
      early Tfh-cell development. Finally, IL-6 promoted parasite control, IgM and IgG
      production, GC B-cell development and ICOS expression by Tfh cells in a second
      model, Py17XNL infection. IL-6 promotes CD4+ T-cell activation and B-cell
      responses during blood-stage Plasmodium infection, which encourages parasite
      specific antibody production.

PMID- 28748531
TI  - Sri Lankan pig ancestry revealed by mitochondrial DNA, Y-chromosome, and MC1R.

PMID- 28748532
TI  - rdxA, frxA, and efflux pump in metronidazole-resistant Helicobacter pylori: Their
      relation to clinical outcomes.
AB  - BACKGROUND AND AIM: rdxA and frxA mutations and enhancement of efflux pump have
      been suggested as the cause of metronidazole resistance in Helicobacter pylori.
      This study was performed to investigate the resistance mechanisms related to
      clinical eradication outcome, and to examine direct involvement of hefA in
      metronidazole-resistant isolates with intact rdxA and frxA. METHODS: A total of
      53 H. pylori-positive patients who were treated with metronidazole-containing
      sequential or quadruple therapy from 2011 to 2015 were enrolled. The
      metronidazole susceptibility of H. pylori isolates was examined by agar dilution
      test. Mutations in rdxA and frxA, were analyzed with DNA sequencing, and impact
      of hefA on metronidazole resistance was examined with quantitative real-time
      reverse transcription polymerase chain reaction, knockout and genetic
      complementation test for hefA. RESULTS: Seven mutation types of rdxA and/or frxA
      were found in H. pylori isolated from non-eradicated subjects. rdxA mutation was
      associated with eradication failure (P = 0.002), and nonsense mutation in rdxA
      reduced eradication efficacy (P = 0.009). hefA expression was significantly
      higher in resistant isolates (P < 0.001), especially in rdxA(-)frxA(-) as
      compared to rdxA(+)frxA(+) (P = 0.027). Resistant isolates with no mutation in
      rdxA and frxA became susceptible after hefA knockout. Genetic complementation for
      hefA recovered metronidazole resistance in all of three hefA knockout mutants.
      CONCLUSIONS: These results suggest that rdxA mutations play a critical role in
      metronidazole resistance as well as the outcomes of eradication therapy. In
      addition, hefA seems to be directly involved in metronidazole resistance, which
      explains the resistance in clinical isolates with intact rdxA and frxA.

PMID- 28748533
TI  - Macrococcus canis and M. caseolyticus in dogs: occurrence, genetic diversity and
      antibiotic resistance.
AB  - BACKGROUND: The discovery of a new Macrococcus canis species isolated from skin
      and infection sites of dogs led us to question if Macrococcus spp. are common in
      dogs and are resistant to antibiotics. HYPOTHESIS/OBJECTIVES: To evaluate the
      occurrence of Macrococcus spp. in dogs, determine antibiotic resistance profiles
      and genetic relationships. ANIMALS: One hundred and sixty two dogs (mainly West
      Highland white terriers and Newfoundland dogs) were screened for the presence of
      Macrococcus, including six dogs with Macrococcus infections. METHODS: Samples
      were taken from skin, ear canal and oral mucosa using swabs. Macrococci were
      identified by matrix-assisted laser desorption ionization-time of flight mass
      spectrometry, 16S rRNA sequencing and nuc-PCR. Minimal inhibitory concentrations
      of 19 antibiotics were determined using broth microdilution. Resistance
      mechanisms were identified by microarray and sequencing of the fluoroquinolone
      determining region of gyrA and grlA. Sequence type (ST) was determined by
      multilocus sequence typing. RESULTS: Out of the 162 dogs, six harboured M.
      caseolyticus (n = 6) and 13 harboured M. canis (n = 16). Six isolates of M. canis
      and one of M. caseolyticus were obtained from infection sites. The 22 M. canis
      strains belonged to 20 different STs and the seven M. caseolyticus strains to
      three STs. Resistance to antibiotics was mostly associated with the detection of
      known genes, with mecB-mediated meticillin resistance being the most frequent.
      CONCLUSION AND CLINICAL IMPORTANCE: This study gives some insights into the
      occurrence and genetic characteristics of antibiotic-resistant Macrococcus from
      dogs. Presence of M. canis in infection sites and resistance to antibiotics
      emphasized that more attention should be paid to this novel bacteria species.

PMID- 28748534
TI  - miR-130b directly targets ARHGAP1 to drive activation of a metastatic CDC42-PAK1
      AP1 positive feedback loop in Ewing sarcoma.
AB  - Ewing Sarcoma (ES) is a highly aggressive bone tumor with peak incidence in the
      adolescent population. It has a high propensity to metastasize, which is
      associated with dismal survival rates of approximately 25%. To further understand
      mechanisms of metastasis we investigated microRNA regulatory networks in ES. Our
      studies focused on miR-130b due to our analysis that enhanced expression of this
      microRNA has clinical relevance in multiple sarcomas, including ES. Our studies
      provide insights into a novel positive feedback network involving the direct
      regulation of miR-130b and activation of downstream signaling events contributing
      toward sarcoma metastasis. Specifically, we demonstrated miR-130b induces
      proliferation, invasion, and migration in vitro and increased metastatic
      potential in vivo. Using microarray analysis of ES cells with differential miR
      130b expression we identified alterations in downstream signaling cascades
      including activation of the CDC42 pathway. We identified ARHGAP1, which is a
      negative regulator of CDC42, as a novel, direct target of miR-130b. In turn,
      downstream activation of PAK1 activated the JNK and AP-1 cascades and downstream
      transcriptional targets including IL-8, MMP1 and CCND1. Furthermore, chromatin
      immunoprecipitation of endogenous AP-1 in ES cells demonstrated direct binding to
      an upstream consensus binding site within the miR-130b promoter. Finally, small
      molecule inhibition of PAK1 blocked miR-130b activation of JNK and downstream AP
      1 target genes, including primary miR-130b transcripts, and miR-130b oncogenic
      properties, thus identifying PAK1 as a novel therapeutic target for ES. Taken
      together, our findings identify and characterize a novel, targetable miR-130b
      regulatory network that promotes ES metastasis.

PMID- 28748535
TI  - Financial Incentives and Physician Practice Participation in Medicare's Value
      Based Reforms.
AB  - OBJECTIVES: To evaluate whether greater experience and success with performance
      incentives among physician practices are related to increased participation in
      Medicare's voluntary value-based payment reforms. DATA SOURCES/STUDY SETTING:
      Publicly available data from Medicare's Physician Compare (n = 1,278; January
      2012 to November 2013) and nationally representative physician practice data from
      the National Survey of Physician Organizations 3 (NSPO3; n = 907,538; 2013).
      STUDY DESIGN: We used regression analysis to examine practice-level relationships
      between prior exposure to performance incentives and participation in key
      Medicare value-based payment reforms: accountable care organization (ACO)
      programs, the Physician Quality Reporting System ("Physician Compare"), and the
      Meaningful Use of Health Information Technology program ("Meaningful Use"). Prior
      experience and success with financial incentives were measured as (1) the
      percentage of practices' revenue from financial incentives for quality or
      efficiency; and (2) practices' exposure to public reporting of quality measures.
      DATA COLLECTION/EXTRACTION METHODS: We linked physician participation data from
      Medicare's Physician Compare to the NSPO3 survey. PRINCIPAL FINDINGS: There was
      wide variation in practices' exposure to performance incentives, with 64 percent
      exposed to financial incentives, 45 percent exposed to public reporting, and 2.2
      percent of practice revenue coming from financial incentives. For each percentage
      point increase in financial incentives, there was a 0.9 percentage-point increase
      in the probability of participating in ACOs (standard error [SE], 0.1, p < .001)
      and a 0.8 percentage-point increase in the probability of participating in
      Meaningful Use (SE, 0.1, p < .001), controlling for practice characteristics.
      Financial incentives were not associated with participation in Physician Compare.
      Among ACO participants, a 1 percentage-point increase in incentives was
      associated with a 0.7 percentage-point increase in the probability of being "very
      well" prepared to utilize cost and quality data (SE, 0.1, p < .001). CONCLUSIONS:
      Physicians organizations' prior experience and success with performance
      incentives were related to participation in Medicare ACO arrangements and
      participation in the meaningful use criteria but not to participation in
      Physician Compare. We conclude that Medicare must complement financial incentives
      with additional efforts to address the needs of practices with less experience
      with such incentives to promote value-based payment on a broader scale.

PMID- 28748536
TI  - Renal tubular injury during cardiopulmonary bypass as assessed by urinary release
      of N-acetyl-beta-D-glucosaminidase.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common complication with a major
      impact on morbidity and mortality after cardiac surgery with cardiopulmonary
      bypass (CPB). The aim of the present study was to perform a detailed analysis on
      the release of the tubular injury biomarker N-acetyl-b-D-glucosaminidase (NAG)
      during and early after CPB and to describe independent predictors of maximal
      tubular injury. We hypothesized that renal tubular injury occurs early after the
      onset of CPB. METHODS: In this prospective observational study, we included 61
      patients undergoing open cardiac surgery with an expected CPB duration exceeding
      60 min. The urinary NAG levels were measured at 30 min intervals during CPB, as
      well as early (30 min) after CPB and post-operatively. Independent predictors of
      tubular injury were identified using an Interquantile multivariate regression
      model. RESULTS: Already 30 min after the onset of CPB, NAG excretion was
      significantly increased (P < 0.001), followed by a sixfold peak increase after
      discontinuation of CPB (P < 0.001). In the multivariable regression model, CPB
      duration (P < 0.05) and the degree of rewarming during CPB (P < 0.05), were
      independent predictors of peak NAG excretion. CONCLUSION: In cardiac surgery, a
      renal tubular cell injury is seen early after onset of CPB with a peak biomarker
      increase early after end of CPB. The magnitude of this tubular injury is
      independently related to CPB duration and the degree of rewarming. Efforts made
      to decrease the CPB duration and to avoid hypothermia and the need for rewarming
      may decrease the risk for tubular injury.

PMID- 28748538
TI  - Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede
      efficient antigen processing and affect the in vivo antibody response.
AB  - Vol. 34(3) 2004, DOI 10.1002/eji.200324514 Due to a technical error, the wrong
      affiliations were given for C. Moss and V. Lindo. These are correct as given
      above. See original article http://dx.doi.org/10.1002/eji.200324514.

PMID- 28748537
TI  - Differences in brain morphology and working memory capacity across childhood.
AB  - Working memory (WM) skills are closely associated with learning progress in key
      areas such as reading and mathematics across childhood. As yet, however, little
      is known about how the brain systems underpinning WM develop over this critical
      developmental period. The current study investigated whether and how structural
      brain correlates of components of the working memory system change over
      development. Verbal and visuospatial short-term and working memory were assessed
      in 153 children between 5.58 and 15.92 years, and latent components of the
      working memory system were derived. Fractional anisotropy and cortical thickness
      maps were derived from T1-weighted and diffusion-weighted MRI and processed using
      eigenanatomy decomposition. There was a greater involvement of the corpus
      callosum and posterior temporal white matter in younger children for performance
      associated with the executive part of the working memory system. For older
      children, this was more closely linked with the thickness of the occipitotemporal
      cortex. These findings suggest that increasing specialization leads to shifts in
      the contribution of neural substrates over childhood, moving from an early
      dependence on a distributed system supported by long-range connections to later
      reliance on specialized local circuitry. Our findings demonstrate that despite
      the component factor structure being stable across childhood, the underlying
      brain systems supporting working memory change. Taking the age of the child into
      account, and not just their overall score, is likely to be critical for
      understanding the nature of the limitations on their working memory capacity.

PMID- 28748539
TI  - Miniprobe Endoscopic Sonography for Gastrointestinal Tract Assessment: A Case
      Series of 1451 Procedures.
AB  - Conventional endoscopic sonography has allowed precise diagnostics without
      disturbances, and miniprobes can be easily introduced through the biopsy channel
      of the endoscope. Miniprobe endoscopic sonography has many benefits compared with
      conventional endoscopic sonography. Although there are well-known indications for
      miniprobe endoscopic sonography in endoscopic digestive tract assessment, there
      is still a need for this method to be widely spread among physicians and commonly
      used by most endoscopists. The aim of this series was to describe a multicenter
      retrospective experience with 1451 procedures using miniprobes, presenting
      examples and the applicability and usefulness of this technology in the daily
      activities of an endoscopy department.

PMID- 28748540
TI  - Particulate matter adheres to human hair exposed to severe aerial pollution:
      consequences for certain hair surface properties.
AB  - BACKGROUND: The deposit and adherence of particulate matter (PM) from aerial
      pollution onto the surface of human hair is a poorly studied phenomenon.
      OBJECTIVES: (i) To reproduce in vitro the deposit of known PM on standardized
      hair swatches in a closed box, (ii) to compare in vitro data with those obtained
      under 'real-life' conditions of severe aerial pollution and (iii) to assess the
      changes of the hair surface properties, potentially caused by the adherence of
      airborne PM onto the hair. METHODS: In vitro: a PM was sprayed onto untreated or
      sebum-coated hair swatches. Real-life conditions: other swatches were exposed to
      a severely polluted environment, for 24 to 72 h, in Baoding (PR China). In both
      cases, swatches were examined using scanning electron microscopy. The shine, the
      frictional properties and the level of metals were measured and compared to those
      same properties for the unexposed swatches. RESULTS: This work clearly indicates
      that, under real-life conditions, a large number of PM of various sizes are
      deposited onto the hair surface. This phenomenon is increased by the presence of
      sebum and longer exposure times. The in vitro level of PM deposited onto the hair
      surface is comparable to the in vivo level. The presence of sebum seems to favour
      the deposit of larger PM. The shine of the exposed swatches is significantly
      decreased, whereas their respective friction coefficients are significantly
      increased. Both the presence of sebum and length of exposure time increased the
      amount of analysed metals present on the exposed hair surface (Al, Fe, Cu, Ba and
      Zn). CONCLUSION: This work indicates that a very high amount (e.g. billions) of
      PM can be deposited on a full head of hair for subjects living in a severely
      aerially polluted environment. This process can be reproduced in vitro. In real
      life, pollution has a strong impact on hair surface properties, leading to a
      modification of the visual aspect (loss of shine) and the alteration of hair
      surface (increase in friction force). This work may be used to pave the way for
      prevention and cleansing studies in the field of hair care.

PMID- 28748541
TI  - Reliable assessment of the incidence of childhood autoimmune hemolytic anemia.
AB  - BACKGROUND: Childhood autoimmune hemolytic anemia (AIHA) is a rare and severe
      disease characterized by hemolysis and positive direct antiglobulin test (DAT).
      Few epidemiologic indicators are available for the pediatric population. The
      objective of our study was to reliably estimate the number of AIHA cases in the
      French Aquitaine region and the incidence of AIHA in patients under 18 years old.
      PROCEDURE: In this retrospective study, the capture-recapture method and log
      linear model were used for the period 2000-2008 in the Aquitaine region from the
      following three data sources for the diagnosis of AIHA: the OBS'CEREVANCE
      database cohort, positive DAT collected from the regional blood bank database,
      and the French medico-economic information system. RESULTS: A list of 281
      different patients was obtained after cross-matching the three databases; 44 AIHA
      cases were identified in the period 2000-2008; and the total number of cases was
      estimated to be 48 (95% confidence interval [CI]: 45-55). The calculated
      incidence of the disease was 0.81/100,000 children under 18 years old per year
      (95% CI 0.76-0.92). CONCLUSION: Accurate methods are required for estimating the
      incidence of AIHA in children. Capture-recapture analysis corrects underreporting
      and provides optimal completeness. This study highlights a possible under
      diagnosis of this potentially severe disease in various pediatric settings. AIHA
      incidence may now be compared with the incidences of other hematological diseases
      and used for clinical or research purposes.

PMID- 28748542
TI  - Pediatric intracerebral histiocytic sarcoma with rhabdoid features: Case report
      and literature review.
AB  - A 16-year-old boy presented with marked weight loss, weakness of the left
      extremities and dizziness of 2 months duration and vomiting for 2 days. Brain MRI
      showed an approximately 6.5 * 5.3 cm-sized huge heterogeneous enhancing mass
      located in the corpus callosum, extending into the lateral ventricle. Open biopsy
      showed that the lesion consisted of lymphoplasmacytes and plump histiocytes with
      rhabdoid morphology, which were stained with S-100 protein, CD68 (KP1) and
      negative for CD1a. Histiocytic tumor was initially diagnosed. Chemotherapy using
      methotrexate, 6-mercaptopurine, vinblastine, interferon-alpha and dexamethasone
      was performed. After 5 months, partial removal was done. Microscopically, plump
      and bizarre tumor cells as well as rhabdoid features were found. Occasional
      spindle cells and necrosis were also found. These cells were positive for CD163,
      CD68, lysozyme, CD4, INI-1 and BRG1. BRAF V600E mutation was detected. The lesion
      was finally diagnosed as histiocytic sarcoma. Radiotherapy (6000 cGy in 30
      fractions) was done. Both cerebral and extracerebral histiocytic sarcomas have
      long been diagnosed by unclarified criteria; its rarity as well as previously
      unclarified criteria can easily lead to a misinterpretation. Histiocytic sarcoma
      of the CNS is exceptionally rare in children, associated with an exceptionally
      poor prognosis. To date, only seven cases of pediatric cerebral histiocytic
      sarcomas have been reported. The present case is the first pediatric case showing
      BRAF V600E-mutated intracerebral histiocytic sarcoma.

PMID- 28748544
TI  - ADF News.

PMID- 28748545
TI  - Underdominant KCC3b R31I association with blood sodium concentration in domestic
      sheep suggests role in oligomer function.

PMID- 28748546
TI  - Photonic Reactions Leading to Fluorescence in a Polymeric System Induced by the
      Photothermal Effect of Magnetite Nanoparticles Using a 780 nm Multiphoton Laser.
AB  - Recently, polymer-coated magnetite (Fe3 O4 ) nanoparticles (NPs) are extensively
      studied for applications in therapeutics or diagnostics using photothermal
      effect. Therefore, it is essential to understand the interactions between Fe3 O4
      NPs and polymers when optical stimuli are applied. Herein, the photonic reactions
      of Fe3 O4 NPs and polymer composites upon application of a 780 nm multiphoton
      laser are analyzed. The photonic reactions produce unique results including
      fluorescence from conformationally changed polymer and low-temperature phase
      transformation of Fe3 O4 NPs. Typically, pi-conjugated chains are formed,
      inducing fluorescence through a series of main and side-chain cleavage reactions
      of polymers with the aliphatic chain. In addition, fluorescence is detected in
      the cellular system by photonic reactions between Fe3 O4 NPs and biomolecules.
      After multiphoton laser irradiation, light emission is detected near the
      intracellular Fe3 O4 NPs, and a stronger intensity is observed in large-sized
      NPs.

PMID- 28748547
TI  - Painful nails and white macules.

PMID- 28748548
TI  - Highly Diastereo- and Enantioselective Synthesis of Tetrahydro-5H-Indolo[2,3
      b]quinolines through Copper-Catalyzed Propargylic Dearomatization of Indoles.
AB  - The first copper-catalyzed intermolecular asymmetric propargylic
      dearomatization/annulation cascade sequence of indoles via a copper-allenylidene
      amphiphilic intermediate has been achieved. This protocol provides a direct
      asymmetric synthetic method for the preparation of tetrahydro-5H-indolo[2,3
      b]quinolines, the core structure of indole alkaloids communesins A-H and
      perophoramidine. This method features excellent yields, high diastereoselectivity
      (up to >19:1 d.r.) and enantioselectivity (up to 94 % ee), mild conditions and
      wide substrate scope.

PMID- 28748549
TI  - Ultrasound Curricula in Undergraduate Medical Education: A Scoping Review.
AB  - The clinical applications of point-of-care ultrasound (US) have expanded rapidly
      over the past decade. To promote early exposure to point-of-care US, there is
      widespread support for the integration of US curricula within undergraduate
      medical education. However, despite growing evidence and enthusiasm for point-of
      care US education in undergraduate medical education, the curricular design and
      delivery across undergraduate medical education programs remain variable without
      widely adopted national standards and guidelines. This article highlights the
      educational and teaching applications of point-of-care US with a focus on
      outcomes. We then review the evidence on curricular design, delivery, and
      integration and the assessment of competency for point-of-care US in
      undergraduate medical education.

PMID- 28748550
TI  - Porcine C-peptide measurement to assess graft function in xenogeneic porcine
      islet transplantation; editorial commentary.

PMID- 28748551
TI  - Identification of a dimeric KDG aldolase from Agrobacterium tumefaciens.
AB  - Agrobacterium tumefaciens is a Gram-negative bacterium and causative agent of
      Crown Gall disease that infects a variety of economically important plants. The
      annotated A. tumefaciens genome contains 10 putative dapA genes, which code for
      dihydrodipicolinate synthase (DHDPS). However, we have recently demonstrated that
      only one of these genes (dapA7) encodes a functional DHDPS. The function of the
      other nine putative dapA genes is yet to be determined. Here, we demonstrate
      using bioinformatics that the product of the dapA5 gene (DapA5) possesses all the
      catalytic residues canonical to 2-keto-3-deoxygluconate (KDG) aldolase, which is
      a class I aldolase involved in glucose metabolism. We therefore expressed,
      purified, and characterized recombinant DapA5 using mass spectrometry, circular
      dichroism spectroscopy, analytical ultracentrifugation, and enzyme kinetics. The
      results show that DapA5 (1) adopts an alpha/beta structure consistent with the
      TIM-barrel fold of KDG aldolases, (2) possesses KDG aldolase enzyme activity, and
      (3) exists as a tight dimer in solution. This study shows for the first time that
      dapA5 from A. tumefaciens encodes a functional dimeric KDG aldolase.

PMID- 28748552
TI  - Erythropoiesis-stimulating agents in sickle cell anaemia.

PMID- 28748553
TI  - Accelerator-free gloves as alternatives in cases of glove allergy in healthcare
      workers.
AB  - BACKGROUND: Accelerators in rubber gloves constitute an important group of
      contact allergens, particularly in healthcare workers. OBJECTIVES: To assess the
      efficacy of accelerator-free medical gloves in the secondary prevention of
      allergic contact dermatitis caused by rubber accelerators in healthcare workers.
      METHODS: Nine healthcare workers with hand eczema were advised to use accelerator
      free rubber gloves after a diagnosis of allergic contact dermatitis caused by
      rubber accelerators. RESULTS: Switching from conventional medical single-use
      gloves containing accelerators to accelerator-free medical gloves led to
      improvement in all cases, and more than two-thirds of the patients were
      completely free of symptoms. CONCLUSION: The use of accelerator-free medical
      gloves can be an effective alternative in healthcare workers who are allergic to
      rubber accelerators.

PMID- 28748554
TI  - Estimation of inbreeding depression on female fertility in the Finnish Ayrshire
      population.
AB  - Single nucleotide polymorphism (SNP) data enable the estimation of inbreeding at
      the genome level. In this study, we estimated inbreeding levels for 19,075
      Finnish Ayrshire cows genotyped with a low-density SNP panel (8K). The genotypes
      were imputed to 50K density, and after quality control, 39,144 SNPs remained for
      the analysis. Inbreeding coefficients were estimated for each animal based on the
      percentage of homozygous SNPs (FPH ), runs of homozygosity (FROH ) and pedigree
      (FPED ). Phenotypic records were available for 13,712 animals including non
      return rate (NRR), number of inseminations (AIS) and interval from first to last
      insemination (IFL) for heifers and up to three parities for cows, as well as
      interval from calving to first insemination (ICF) for cows. Average FPED was
      0.02, FROH 0.06 and FPH 0.63. A correlation of 0.71 was found between FPED and
      FROH , 0.66 between FPED and FPH and 0.94 between FROH and FPH . Pedigree-based
      inbreeding coefficients did not show inbreeding depression in any of the traits.
      However, when FROH or FPH was used as a covariate, significant inbreeding
      depression was observed; a 10% increase in FROH was associated with 5 days longer
      IFL0 and IFL1, 2 weeks longer IFL3 and 3 days longer ICF2 compared to non-inbred
      cows.

PMID- 28748555
TI  - Digitalis use and lung cancer risk by histological type in men.
AB  - Lung cancer risk and tumor characteristics differ between sexes. Estrogen has
      been suggested to counteract lung cancer development. We aimed to test the
      hypothesis that digitalis use decreases lung cancer risk due to its estrogenic
      and other anticancer properties in men. This was a nationwide Swedish population
      based cohort study between July 1, 2005 and December 31, 2013. Data on the use of
      digitalis and organic nitrates in all male individuals were derived from the
      Swedish Prescribed Drug Registry. New lung cancer diagnoses among cohort
      participants were identified from the Swedish Cancer Registry. Cox proportional
      hazards regression was employed to estimate hazard ratios (HRs) with 95%
      confidence intervals (CIs) of lung cancer in digitalis users (exposed
      participants) compared to users of organic nitrates without digitalis medication
      (unexposed participants). The study cohort contained 74,437 digitalis users and
      297,301 organic nitrates users. Long-term use (>=2 years) of digitalis was
      associated with decreased HRs of total lung cancer (HR 0.55, 95% CI 0.39-0.79)
      and squamous cell carcinoma (HR 0.40, 95% CI 0.19-0.87). This large and
      population-based study suggests decreased risks of lung cancer overall and
      squamous cell carcinoma associated with long-term use of digitalis in men.

PMID- 28748557
TI  - Mood and anxiety disorders in very preterm/very low-birth weight individuals from
      6 to 26 years.
AB  - BACKGROUND: Very preterm (<32 weeks' gestational age; VP) or very low-birth
      weight (<1,500 g; VLBW) birth has been associated with increased risk for anxiety
      and mood disorders and less partnering in adulthood. The aim was to test whether
      (a) VP/VLBW are at increased risk of any anxiety or mood disorders from 6 to 26
      years compared with term-born individuals; (b) social support from romantic
      partners is associated with protection from anxiety and mood disorders; and (c)
      VP/VLBW adults' lower social support mediates their risk for any anxiety and mood
      disorders. METHODS: Data are from a prospective geographically defined
      longitudinal whole-population study in South Bavaria (Germany). Two hundred
      VP/VLBW and 197 term individuals were studied from birth to adulthood. Anxiety
      and mood disorders were assessed at 6, 8, and 26 years with standardized
      diagnostic interviews and social support via self-report at age 26. RESULTS: At
      age 6, VP/VLBW children were not at increased risk of any anxiety or mood
      disorder. At age 8, VP/VLBW more often had any anxiety disorder than term
      comparisons (11.8% vs. 6.6%, OR = 2.10, 95% CI [1.08-4.10]). VP/VLBW adults had
      an increased risk for any mood (27.5% vs. 18.8%, OR = 1.65 [1.02-2.67]) but not
      for any anxiety disorder (33.0% vs. 28.4%, OR = 1.27 [0.82-1.96]). None of the
      significant differences survived correction for multiple testing. Social support
      was associated with a lower risk of anxiety or mood disorders in both groups (OR
      = 0.81 [0.68-0.96]) and mediated the association of VP/VLBW birth with any
      anxiety or any mood disorders at age 26. CONCLUSIONS: This study does not show a
      persistently increased risk for any anxiety or mood disorder after VP/VLBW birth.
      Low social support from a romantic partner mediates the risk for anxiety or mood
      disorders after VP/VLBW birth.

PMID- 28748556
TI  - Systemic therapy treatment patterns in patients with advanced non-small cell lung
      cancer (NSCLC): PIvOTAL study.
AB  - The aim of this multinational retrospective cohort study, conducted at academic
      and community oncology centres, was to describe real-world treatment patterns for
      patients with a confirmed diagnosis of advanced/metastatic (stage IIIB/IV) non
      small cell lung cancer (NSCLC) who initiated first-line systemic therapy from
      January 2011 through June 2014. The study included 1265 patients in Italy, Spain,
      Germany, Australia, Korea, Taiwan and Brazil. The proportion of patients with
      squamous versus non-squamous NSCLC was approximately 20% versus 75%, and
      associated patient demographic characteristics were similar in all countries,
      excepting race. Patients with squamous NSCLC were predominantly male and
      current/ex-smokers. Biomarker tests were performed for the majority of patients
      with non-squamous NSCLC, ranging from 54% (Brazil) to 91% in Taiwan, where, of
      those tested, 68% with non-squamous NSCLC had positive epidermal growth factor
      receptor (EGFR)-mutation status; in other countries the EGFR-positive percentages
      ranged from 17% (Spain/Brazil) to 40% (Korea). Platinum-based regimens were the
      most common first-line therapy in all countries except Taiwan, where gefitinib
      was the most common first-line agent. Median overall survival ranged from 9.3
      months (Brazil) to 25.5 months (Taiwan). The diagnostic and treatment patterns
      recorded in this study were heterogeneous but largely in line with NSCLC
      guidelines during the study period.

PMID- 28748558
TI  - Aggressive B-cell lymphomas in the update of the 4th edition of the World Health
      Organization classification of haematopoietic and lymphatic tissues: refinements
      of the classification, new entities and genetic findings.
AB  - The update of the 4th edition of the World Health Organization Classification of
      Haematopoietic and Lymphatic Tissues portends important new findings and concepts
      in the diagnosis, classification and biology of lymphomas. This review summarizes
      the basic concepts and cornerstones of the classification of aggressive B-cell
      lymphomas and details the major changes. Of importance, there is a new concept of
      High-grade B-cell lymphomas (HGBL), partly replacing the provisional entity of B
      cell lymphoma, unclassifiable, with features intermediate between diffuse large B
      cell lymphoma (DLBCL) and Burkitt lymphoma, the so-called grey zone lymphomas.
      They either harbour MYC translocations together with a BCL2 and/or a BCL6
      rearrangement (HGBL-Double Hit) or HGBL, not otherwise specified (NOS), lacking a
      double or triple hit constellation. In addition, the requirement for providing
      the cell-of-origin classification in the diagnostic work-up of DLBCLs, the role
      of MYC alterations in DLBCL subtypes, and newer findings in the specific
      variants/subtypes are highlighted.

PMID- 28748559
TI  - Introduction of 2,6-Diaminopurines into Serinol Nucleic Acid Improves Anti-miRNA
      Performance.
AB  - MicroRNAs (miRNAs) are endogenous small RNAs that regulate gene expression at the
      post-transcriptional level by sequence-specific hybridisation. Anti-miRNA
      oligonucleotides (AMOs) are inhibitors of miRNA activity. Chemical modification
      of AMOs is required to increase binding affinity and stability in serum and
      cells. In this study, we synthesised AMOs with our original acyclic nucleic acid,
      serinol nucleic acid (SNA), backbone and with the artificial nucleobase 2,6
      diaminopurine. The AMO composed of only SNA had strong nuclease resistance and
      blocked endogenous miRNA activity. A significant improvement in anti-miRNA
      activity of the AMO was achieved by introduction of a 2,6-diaminopurine residues
      into the SNA backbone. In addition, we found that the enhancement in AMO activity
      depended on the position of the 2,6-diaminopurine residue in the sequence. The
      high potency of the SNA-AMOs suggests that these oligomers will be useful as
      therapeutic reagents for control of miRNA function in patients and as tools for
      investigating the roles of microRNAs in cells.

PMID- 28748560
TI  - Results of allergen-specific immunotherapy in atopic dogs with Malassezia
      hypersensitivity: a retrospective study of 16 cases.
AB  - BACKGROUND: Hypersensitivity reactions to Malassezia spp have been shown to occur
      in dogs with atopic dermatitis (AD) and to cause exacerbation of clinical signs.
      Improvement of clinical signs following use of antifungal medication is seen with
      both Malassezia overgrowth or Malassezia hypersensitivity (MHS). Subcutaneous
      immunotherapy (SCIT) is considered a safe and effective treatment for management
      of canine AD. Adverse effects are considered rare. OBJECTIVES: To report on the
      use of SCIT with Malassezia extracts in mono-sensitized dogs. ANIMALS: Sixteen
      client owned dogs diagnosed with MHS and treated with SCIT. METHODS: A
      retrospective review of medical records of atopic dogs diagnosed with MHS, mono
      sensitized for Malassezia allergens on intradermal test and treated with SCIT for
      more than 10 months. Efficacy was measured by decreasing use of anti-inflammatory
      and antifungal medication by >=50% and by decreasing pruritus by >=50% as
      assessed by owners, using a pruritus score. RESULTS: Good response to SCIT was
      seen in nine of 16 cases (56%) with both a reduction in use of anti-inflammatory
      and antifungal medication as well as a reduction in pruritus scores by >=50%. No
      adverse effects were reported. CONCLUSION: Allergen-specific immunotherapy was a
      safe treatment for dogs with Malassezia hypersensitivity. The efficacy of
      Malassezia immunotherapy corresponds well to the results of previous studies of
      immunotherapy with other environmental allergens.

PMID- 28748561
TI  - Evidence that auxin is required for normal seed size and starch synthesis in pea.
AB  - In recent years the biosynthesis of auxin has been clarified with the aid of
      mutations in auxin biosynthesis genes. However, we know little about the effects
      of these mutations on the seed-filling stage of seed development. Here we
      investigate a key auxin biosynthesis mutation of the garden pea, which results in
      auxin deficiency in developing seeds. We exploit the large seed size of this
      model species, which facilitates the measurement of compounds in individual
      seeds. The mutation results in small seeds with reduced starch content and a
      wrinkled phenotype at the dry stage. The phenotypic effects of the mutation were
      fully reversed by introduction of the wild-type gene as a transgene, and
      partially reversed by auxin application. The results indicate that auxin is
      required for normal seed size and starch accumulation in pea, an important grain
      legume crop.

PMID- 28748562
TI  - Visualization of macrophage recruitment in head and neck carcinoma model using
      fluorine-19 magnetic resonance imaging.
AB  - PURPOSE: To evaluate the role of infiltrating macrophages in murine models of
      single and double mutation head and neck tumors using a novel fluorine-19 (19 F)
      MRI technology. METHODS: Tumor cell lines single-hit/SCC4 or double-hit/Cal27,
      with mutations of TP53 and TP53 & FHIT, respectively, were injected bilaterally
      into the flanks of (n = 10) female mice. With tumors established, perfluorocarbon
      nanoemulsion was injected intravenously, which labels in situ predominantly
      monocytes and macrophages. Longitudinal spin density-weighted 19 F MRI data
      enabled quantification of the macrophage burden in tumor and surrounding tissue.
      RESULTS: The average number of 19 F atoms within the tumors was twice as high in
      the Cal27 group compared with SCC4 (3.9 * 1019 and 2.0 * 101919 F/tumor,
      respectively; P = 0.0034) two days after contrast injection, signifying increased
      tumor-associated macrophages in double-hit tumors. The difference was still
      significant 10 days after injection. Histology stains correlated with in vivo
      results, exhibiting numerous perfluorocarbon-labeled macrophages in double-hit
      tumors and to a lesser extent in single-hit tumors. CONCLUSIONS: This study helps
      to establish 19 F MRI as a method for quantifying immune cells in the tumor
      microenvironment, allowing distinction between double and single-hit head and
      neck tumors. This technique would be extremely valuable in the clinic for
      pretreatment planning, prognostics, and post-treatment surveillance. Magn Reson
      Med 79:1972-1980, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 28748563
TI  - Intrahospital transfers and adverse patient outcomes: An analysis of
      administrative health data.
AB  - AIMS AND OBJECTIVES: To determine whether there was an association between intra
      hospital transfers and adverse outcomes. BACKGROUND: Transfers between clinical
      units and between beds on the same unit are routine aspects of an episode of care
      in acute hospitals. The rate of these transfers per episode has increased in
      response to high occupancy levels, a decline in bed numbers, and increased demand
      for hospital services. The impact of the number of transfers between both wards
      and beds on patient outcomes is not widely explored. DESIGN: Retrospective cross
      sectional design using hospital administrative data. METHOD: Data were extracted
      from existing hospital administrative datasets for one large metropolitan
      hospital for the financial year 2008-09 in Australia (n = 14,133). Descriptive
      analyses and logistic regression models were developed for each of 3 selected
      patient outcomes. RESULTS: Nearly one-tenth of patients (9.2%) experienced a fall
      with injury, 3.8% of surgical patients a wound infection and 0.1% a complication
      from medication errors. For each bed or ward transfer, the odds of falls and
      wound infections increased. Medication errors were not associated with either bed
      or ward moves. CONCLUSION: Hospitals should minimise the number of bed and ward
      transfers per episode of care in order to reduce the likelihood of adverse
      patient outcomes. Current bed management policies and practices should be
      evaluated and further refined to address this need. Additional strategies include
      improving coordination and communication during and after transfer. RELEVANCE TO
      CLINICAL PRACTICE: Nurses must consider the potential cost of intrahospital
      transfers on patients, length of stay and bed availability.

PMID- 28748564
TI  - Medicare Spending for Breast, Prostate, Lung, and Colorectal Cancer Patients in
      the Year of Diagnosis and Year of Death.
AB  - OBJECTIVE: To characterize spending patterns for Medicare patients with incident
      breast, prostate, lung, and colorectal cancer. DATA SOURCES/STUDY SETTING/STUDY
      DESIGN: 2007-2012 data from the Surveillance, Epidemiology, and End Results
      Program linked with Medicare fee-for-service claims. DATA COLLECTION/EXTRACTION
      METHODS: We calculate per-patient monthly and yearly mean and median
      expenditures, by cancer type, stage at diagnosis, and spending category, over the
      years of diagnosis and death. PRINCIPAL FINDINGS: Over the year of diagnosis,
      mean spending was $35,849, $26,295, $55,597, and $63,063 for breast, prostate,
      lung, and colorectal cancer, respectively. Over the year of death, spending was
      similar across different cancer types and stage at diagnosis. CONCLUSIONS:
      Characterization of Medicare spending according to clinically meaningful
      categories may assist development of oncology alternative payment models and cost
      effectiveness models.

PMID- 28748565
TI  - Evaluating mechanisms of diversification in a Guineo-Congolian tropical forest
      frog using demographic model selection.
AB  - The accumulation of biodiversity in tropical forests can occur through multiple
      allopatric and parapatric models of diversification, including forest refugia,
      riverine barriers and ecological gradients. Considerable debate surrounds the
      major diversification process, particularly in the West African Lower Guinea
      forests, which contain a complex geographic arrangement of topographic features
      and historical refugia. We used genomic data to investigate alternative
      mechanisms of diversification in the Gaboon forest frog, Scotobleps gabonicus, by
      first identifying population structure and then performing demographic model
      selection and spatially explicit analyses. We found that a majority of population
      divergences are best explained by allopatric models consistent with the forest
      refugia hypothesis and involve divergence in isolation with subsequent expansion
      and gene flow. These population divergences occurred simultaneously and conform
      to predictions based on climatically stable regions inferred through ecological
      niche modelling. Although forest refugia played a prominent role in the
      intraspecific diversification of S. gabonicus, we also find evidence for
      potential interactions between landscape features and historical refugia,
      including major rivers and elevational barriers such as the Cameroonian Volcanic
      Line. We outline the advantages of using genomewide variation in a model-testing
      framework to distinguish between alternative allopatric hypotheses, and the
      pitfalls of limited geographic and molecular sampling. Although phylogeographic
      patterns are often species-specific and related to life-history traits,
      additional comparative studies incorporating genomic data are necessary for
      separating shared historical processes from idiosyncratic responses to
      environmental, climatic and geological influences on diversification.

PMID- 28748566
TI  - Application of whole-exome sequencing to direct the specific functional testing
      and diagnosis of rare inherited bleeding disorders in patients from the Oresund
      Region, Scandinavia.
AB  - Rare inherited bleeding disorders (IBD) are a common cause of bleeding tendency.
      To ensure a correct diagnosis, specialized laboratory analyses are necessary.
      This study reports the results of an upfront diagnostic strategy using targeted
      whole exome sequencing. In total, 156 patients with a significant bleeding
      assessment tool score participated in the study, of which a third had
      thrombocytopenia. Eighty-seven genes specifically associated with genetic
      predisposition to bleeding were analysed by whole exome sequencing. Variants were
      classified according to the five-tier scheme. We identified 353 germline
      variants. Eight patients (5%) harboured a known pathogenic variant. Of the 345
      previously unknown variants, computational analyses predicted 99 to be
      significant. Further filtration according to the Mendelian inheritance pattern,
      resulted in 59 variants being predicted to be clinically significant. Moreover,
      34% (20/59) were assigned as novel class 4 or 5 variants upon targeted functional
      testing. A class 4 or 5 variant was identified in 30% of patients with
      thrombocytopenia (14/47) versus 11% of patients with a normal platelet count
      (12/109) (P < 0.01). An IBD diagnosis has a major clinical impact. The genetic
      investigations detailed here extricated our patients from a diagnostic conundrum,
      thus demonstrating that continuous optimization of the diagnostic work-up of IBD
      is of great benefit.

PMID- 28748568
TI  - Quantitative studies of rhubarb using quantitative analysis of multicomponents by
      single marker and response surface methodology.
AB  - In this work, we developed a novel approach to evaluate the contents of bioactive
      components in rhubarb. The present method was based on the quantitative analysis
      of multicomponents by a single-marker and response surface methodology
      approaches. The quantitative analysis of multicomponents by a single-marker
      method based on high-performance liquid chromatography coupled with photodiode
      array detection was developed and applied to determine the contents of 12
      bioactive components in rhubarb. No significant differences were found in the
      results from the quantitative analysis of multicomponents by a single-marker and
      the external standard method. In order to maximize the extraction of 12 bioactive
      compounds in rhubarb, the ultrasonic-assisted extraction conditions were obtained
      by the response surface methodology coupled with Box-Behnken design. According to
      the obtained results, we showed that the optimal conditions would be as follows:
      proportion of ethanol/water 74.39%, solvent-to-solid ratio 24.07:1 v/w,
      extraction time 51.13 min, and extraction temperature 63.61 degrees C. The
      analytical scheme established in this research should be a reliable, convenient,
      and appropriate method for quantitative determination of bioactive compounds in
      rhubarb.

PMID- 28748567
TI  - The Hartung-Knapp modification for random-effects meta-analysis: A useful
      refinement but are there any residual concerns?
AB  - The modified method for random-effects meta-analysis, usually attributed to
      Hartung and Knapp and also proposed by Sidik and Jonkman, is easy to implement
      and is becoming advocated for general use. Here, we examine a range of potential
      concerns about the widespread adoption of this method. Motivated by these issues,
      a variety of different conventions can be adopted when using the modified method
      in practice. We describe and investigate the use of a variety of these
      conventions using a new taxonomy of meta-analysis datasets. We conclude that the
      Hartung and Knapp modification may be a suitable replacement for the standard
      method. Despite this, analysts who advocate the modified method should be ready
      to defend its use against the possible objections to it that we present. We
      further recommend that the results from more conventional approaches should be
      used as sensitivity analyses when using the modified method. It has previously
      been suggested that a common-effect analysis should be used for this purpose but
      we suggest amending this recommendation and argue that a standard random-effects
      analysis should be used instead.

PMID- 28748569
TI  - Copper-Catalyzed Amination of Congested and Functionalized alpha
      Bromocarboxamides with either Amines or Ammonia at Room Temperature.
AB  - There are several reports on the synthesis of alkylamines, but most of the
      reported methods are not suitable for the synthesis of hindered amines. In this
      research, we found that a copper catalyst is effective for the formation of
      congested C-N bonds at room temperature. Control experiments revealed that a
      copper amide is a key intermediate. Moreover, when a chiral amine was used, a
      quaternary carbon stereogenic center was created with good selectivity.

PMID- 28748570
TI  - Lichen planopilaris in a Latin American (Chilean) population: demographics,
      clinical profile and treatment experience.
AB  - BACKGROUND: Lichen planopilaris (LPP) is characterized by lymphocytic infiltrate,
      fibrosis and potential destruction of the hair follicle. Demographic and clinical
      studies in LPP are limited, and racial differences have not been thoroughly
      investigated. AIM: To analyse epidemiological data and clinical profiles of
      Chilean adults with LPP, and report on the treatments used. METHODS: This was a
      retrospective review of medical records and clinical follow-up of Chilean adults
      with a clinical and histopathological diagnosis of LPP. Treatment response was
      categorized clinically as none (with progression of condition), mild or
      satisfactory. RESULTS: The study assessed 103 patients with LPP [67 women (mean
      age 54.1 years) and 36 men (mean age 39.1 years)]. Of the 103 patients, 41 women
      and 34 men were diagnosed with classic LPP (CLPP) and 26 women and 1 man with
      frontal fibrosing alopecia (FFA), while Graham-Little-Piccardi-Lassueur syndrome
      (GLPLS) was identified in 1 man. Men with CLPP had a significantly (P < 0.001)
      earlier age of onset than women. Scalp dysaesthesia, erythema and peripilar
      hyperkeratosis were common findings, and 51 (66%) of patients with CLPP had
      cicatricial patches, most of which were circumscribed in the vertex area. All
      patients with FFA had band-like scarring in the frontal and temporal hairlines.
      Morbidities associated with LPP were hypothyroidism, dyslipidaemia, hypertension
      and depression. For most patients, treatment halted or improved their
      inflammatory/scarring condition. A sustained combination of at least one topical
      (clobetasol, minoxidil and salicylic acid) and one systemic (cetirizine,
      hydroxychloroquine, finasteride, methotrexate and isotretinoin) medication was
      necessary in all of our patients with LPP. CONCLUSION: This investigation is one
      of the first to describe the demographic, clinical and therapeutic features of
      LPP in a Latin American population. Similar profiles to previous reports may
      encourage research in larger multicentre international studies.

PMID- 28748571
TI  - Follicular porokeratosis: four new cases.
AB  - Porokeratosis, a disorder of keratinisation, is clinically characterized by the
      presence of annular plaques with a surrounding keratotic ridge. Clinical variants
      include linear, disseminated superficial actinic, verrucous/hypertrophic,
      disseminated eruptive, palmoplantar and porokeratosis of Mibelli (one or two
      typical plaques with atrophic centre and guttered keratotic rim). All of these
      subtypes share the histological feature of a cornoid lamella, characterized by a
      column of 'stacked' parakeratosis with focal absence of the granular layer, and
      dysmaturation (prematurely keratinised cells in the upper spinous layer). In
      recent years, a proposed new subtype, follicular porokeratosis (FP_, has been
      described, in which the cornoid lamella are exclusively located in the follicular
      ostia. We present four new cases that showed typical histological features of FP.

PMID- 28748572
TI  - Let's chat: developmental neural bases of social motivation during real-time peer
      interaction.
AB  - Humans are motivated to interact with each other, but the neural bases of social
      motivation have been predominantly examined in non-interactive contexts.
      Understanding real-world social motivation is of special importance during middle
      childhood (ages 8-12), a period when social skills improve, social networks grow,
      and social brain networks specialize. To assess interactive social motivation,
      the current study used a novel fMRI paradigm in which children believed they were
      chatting with a peer. The design targeted two phases of interaction: (1)
      Initiation, in which children engaged in a social bid via sharing a like or
      hobby, and (2) Reply, in which children received either an engaged ("Me too") or
      non-engaged ("I'm away") reply from the peer. On control trials, children were
      told that their answers were not shared and that they would receive either
      engaged ("Matched") or non-engaged ("Disconnected") replies from the computer.
      Results indicated that during Initiation and Reply, key components of reward
      circuitry (e.g., ventral striatum) were more active for the peer than the
      computer trials. In addition, during Reply, social cognitive regions were more
      activated by the peer, and this social cognitive specialization increased with
      age. Finally, the effect of engagement type on reward circuitry activation was
      larger for social than non-social trials, indicating developmental sensitivity to
      social contingency. These findings demonstrate that both reward and social
      cognitive brain systems support real-time social interaction in middle childhood.
      An interactive approach to understanding social reward has implications for
      clinical disorders, where social motivation is more affected in real-world
      contexts.

PMID- 28748573
TI  - A novel humanized anti-tumor necrosis factor-related apoptosis-inducing ligand-R2
      monoclonal antibody induces apoptotic and autophagic cell death.
AB  - It is well known that the tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL/TNFSF10) is specifically expressed in various tumor cells, but less or no
      expression in most normal tissues and cells. While TRAIL engages with its native
      death receptors, TRAIL receptor 1 (TRAIL-R1) or 2 (TRAIL-R2), usually elicits the
      tumor cell death by apoptosis. In this study, we report that a novel humanized
      monoclonal antibody against TRAIL-R2 (named as zaptuzumab) well remain the
      biological activity of the parental mouse antibody AD5-10 inducing cell death in
      various cancer cells, but little effect on normal cells. Zaptuzumab also markedly
      inhibited the tumor growth in the mouse xenograft of NCI-H460 without toxicity to
      the liver and kidney, and the efficacy of tumor suppression was increased
      significantly while it combined with cis-dichlorodiamineplatinum. Especially, 131
      I-labeled zaptuzumab injected into mouse tail vein specifically targeted to the
      xenograft of the lung cancer cells. Confocal analysis showed that zaptuzumab
      bound with TRAIL-R2 on cell surface could be quickly internalized and transferred
      into the lysosome. Furthermore, zaptuzumab possessed a high level of antibody
      dependent cytotoxicity as well as complement-dependent cytotoxicity. Study on the
      mechanisms of cell death induced by zaptuzumab showed that it efficiently induced
      both caspase-dependent apoptosis and autophagic cell death. These data suggest
      that the humanized anti-TRAIL-R2 monoclonal antibody or the second generation of
      the antibody may have an important clinical usage for cancer immunotherapy. (c)
      2017 IUBMB Life, 69(9):735-744, 2017.

PMID- 28748574
TI  - Delayed postoperative diet is associated with a greater incidence of prolonged
      postoperative ileus and longer stay in hospital for patients undergoing
      gastrointestinal surgery.
AB  - AIM: Recent evidence favours a move away from delaying postoperative nutrition
      towards early feeding practices for better patient outcomes after
      gastrointestinal surgery. The aim of the present study was to investigate
      postoperative diet progression and patient outcomes in a secondary hospital with
      a view to inform future practice. METHODS: This was a retrospective study of
      gastrointestinal surgery patients (n = 69) at a Western Australian general
      hospital. Demographic data and outcomes were collected from patient records and
      included presence or absence of prolonged postoperative ileus, length of stay in
      hospital, days on minimal nutrition and days until first flatus or stool.
      RESULTS: A significant positive association was observed between number of days a
      patient remained on minimal nutrition and length of stay in the overall group (r
      = 0.66, P < 0.01). Patients who developed prolonged postoperative ileus (n = 18,
      26%) had a greater number of days on minimal nutrition (20.0 vs 8.0 days, P <
      0.01), longer stay in hospital (15.0 vs 8.0 days, P < 0.01) and increased number
      of days to first flatus or stool (4.0 vs 2.4 days, P < 0.01) compared with those
      who did not develop prolonged postoperative ileus (n = 51, 74%). CONCLUSIONS:
      This retrospective study of current practice in a secondary-care general hospital
      highlights the gap between traditional care and the improved outcomes reported in
      the literature when early feeding practices are adopted after GI surgery. Further
      investigation of barriers and enablers is necessary to provide insight into
      developing the most appropriate strategy to achieve this.

PMID- 28748575
TI  - Kidney transplantation in Ghana: Is the public ready?
AB  - BACKGROUND: The burden of end stage renal disease (ESRD) is reported to be higher
      among people of African ancestry. The majority do not have access to kidney
      transplantation. Africans, in general, are less likely to donate a kidney or
      receive a transplant. AIMS: This study surveyed public perceptions of kidney
      transplantation in an inner city and suburban communities in Ghana. It examined
      people's willingness to either accept or donate a kidney to save a life. In
      addition, it evaluated factors that influenced their opinion on the issue.
      METHODS: A cross-sectional survey was conducted in five purposively selected
      communities in the Greater Accra region in Ghana. Structured questionnaires and
      standardized instruments were administered to assess participants' socio
      demographic characteristics, religiosity and spirituality, and perception of
      kidney transplantation. RESULTS: Of the 480 participants, 233 (48.5%) were
      willing to donate a kidney; 71.6% would only do so after death. Religion, loss of
      body part, and cultural values influenced participants' willingness to donate a
      kidney. Uncertainty of health status post-transplantation and uneasiness with the
      concept of transplantation influenced the participants' willingness to accept a
      kidney transplant. CONCLUSION: The study revealed that almost half of the
      participants hold positive views toward kidney transplantation.

PMID- 28748576
TI  - Clinical guidelines for male lower urinary tract symptoms and benign prostatic
      hyperplasia.
AB  - The present article is the abbreviated English translation of the Japanese
      guidelines for male lower urinary tract symptoms and benign prostatic hyperplasia
      updated as of the end of 2016. The target patients are men aged >50 years
      complaining of lower urinary tract symptoms, with or without benign prostatic
      hyperplasia, and the target readers are non-urological general physicians and
      urologists. Mandatory assessment for general physicians is medical history,
      physical examination, urinalysis and measurement of serum prostate-specific
      antigen. Additional mandatory assessment for urologists is symptoms and quality
      of life assessment by questionnaires, uroflowmetry, residual urine measurement,
      and prostate ultrasonography. Nocturia requires special attention, as it can
      result from nocturnal polyuria and/or sleep disturbance rather than lower urinary
      tract disorders. Functional lower urinary tract disorders with or without benign
      prostatic hyperplasia are primarily managed by conservative therapy and
      medications, such as alpha1 -blockers and phosphodiesterase-type 5 inhibitors.
      Use of other medications or combination pharmacotherapy is to be reserved for
      urologists. 5alpha-Reductase inhibitors and anticholinergics or beta3 agonists
      are indicated for men with enlarged prostates and overactive bladder symptoms,
      respectively. Surgical intervention for bladder outlet obstruction is considered
      for persistent symptoms or benign prostatic hyperplasia-related comorbidities.
      Surgical modalities should be optimized by the patient's characteristics,
      performance of equipment and the surgeon's experience.

PMID- 28748577
TI  - Selective Conversion of P=O-Bridged Rhodamines into P=O-Rhodols: Solvatochromic
      Near-Infrared Fluorophores.
AB  - The substitution of an oxygen atom in rhodols with a phosphine oxide (P=O) moiety
      affords P=O-bridged rhodols as a new type of near-infrared (NIR) fluorophore.
      This compound class can be readily accessed upon exposure of the corresponding
      rhodamines to aqueous basic conditions. The electron-withdrawing effect of the
      P=O group facilitates the hydrolytic deamination, and, moreover, prolonged
      exposure to aqueous basic conditions generates P=O-bridged fluoresceins, that is,
      a series of three P=O-bridged xanthene dyes is available in one simple operation.
      The P=O-bridged rhodols show significant bathochromic shifts of the longest
      wavelength absorption maximum (Deltalambda=125 nm; >3600 cm-1 ) upon changing the
      solvent from toluene to water, whereas the emission is shifted less drastically
      (Deltalambda=70 nm; 1600 cm-1 ). The hydrogen bonding between the P=O and C=O
      groups with protic solvents results in substantial stabilization of the LUMO
      level, which is responsible for the solvatochromism.

PMID- 28748578
TI  - Exploring quality of life of children with cerebral palsy and intellectual
      disability: What are the important domains of life?
AB  - BACKGROUND: Although it is estimated that half of all children with cerebral
      palsy also have comorbid intellectual disability, the domains of quality of life
      (QOL) important for these children are not well understood. The aim of this study
      was to identify important domains of QOL for these children and adolescents.
      METHODS: Due to the children's communication impairments, qualitative semi
      structured interviews were conducted with 18 parents. The children (9 males) had
      a median age of 12 (range 7 to 17) years at interview and nearly two thirds were
      classified as Gross Motor Function Classification System IV or V. A grounded
      theory approach was used to identify domains of QOL. RESULTS: The 11 domains
      identified as important to QOL were physical health, body comfort, behaviour and
      emotion, communication, predictability and routine, movement and physical
      activity, nature and outdoors, variety of activity, independence and autonomy,
      social connectedness, and access to services. CONCLUSIONS: The domains of QOL
      that emerged from this study will be useful for professionals who support
      children with cerebral palsy and their families. They will also be important for
      developing a QOL instrument essential for informing the development of
      interventions and their monitoring and evaluation.

PMID- 28748579
TI  - New approach applying a pet fish air pump in liquid-phase microextraction for the
      determination of Sudan dyes in food samples by HPLC.
AB  - A new approach applying a pet fish air pump is introduced to develop an
      extraction method, namely, air-pump-enhanced emulsion, followed by salt-assisted
      emulsion breaking based on solidified floating organic drop microextraction for
      the extraction and preconcentration of Sudan I-IV before high-performance liquid
      chromatography. The applicability of this method was successfully demonstrated by
      determination of these dyes in four chili products that include chili powder,
      chili oil, chili sauce, and chili paste. An enrichment factor of 62 was obtained
      only with a sample solution of 5 mL. A linear range of 0.5-2500 ng/mL was
      obtained with a limit of detection of 0.16-0.24 ng/mL and recovery of 90-110%.
      This method is superior to other liquid-liquid extraction methods, as is simple,
      rapid, environmental friendly, and its phase separation needs no centrifugation.
      It also needs no disperser solvent and requires less organic solvent, and
      satisfies the criteria to be called as a green extraction. Therefore, this facile
      extraction method can be successfully applied in the determination of Sudan dyes
      in food samples.

PMID- 28748580
TI  - TiO2 Feather Duster as Effective Polysulfides Restrictor for Enhanced
      Electrochemical Kinetics in Lithium-Sulfur Batteries.
AB  - The rechargeable lithium-sulfur battery is recognized as a promising candidate
      for electrochemical energy storage system because of their exceptional advance in
      energy density. However, the fast capacity decay of sulfur cathode caused by
      polysulfide dissolution and low specific capacity caused by poor electrical
      conductivity still impede the further development of lithium-sulfur battery. To
      address above issues, this study reports the synthesis of feather duster-like
      TiO2 architecture by in situ growth of TiO2 nanowires on carbon cloth and further
      evaluates as sulfur host material. The strong chemical binding interaction
      between the polysulfides and TiO2 feather duster efficiently restrains the
      shuttle effect, leading to enhanced electrochemical kinetics. Besides, the in
      situ grown TiO2 NWs array also supply high surface for sulfur-loading and fast
      path for electron transfer and ion diffusion. As results, the novel CC/TiO2 /S
      composite cathode exhibits a high capacity of 608 mA h g-1 at 1.0 C after 700
      cycles corresponding to capacity decay as low as 0.045% per cycle with excellent
      Coulombic efficiency higher than 99.5%.

PMID- 28748582
TI  - Extravasal albumin concentration modulates contractile responses of renal
      afferent arterioles.
AB  - AIM: Afferent arterioles (AA) hold a key position in the regulation of renal
      blood flow and glomerular filtration rate. Being the effector site of
      tubuloglomerular feedback, the afferent arteriole contributes to the renal
      handling of sodium and fluid. Dehydration goes along with increased renal
      interstitial protein concentration. Here, the hypothesis was tested that
      extravasal protein concentration directly modulates afferent arteriolar tone, a
      mechanism which may contribute to body fluid volume control. METHOD: The effect
      of increased extravasal albumin concentration on the vascular reactivity was
      investigated in renal AA and interlobar arteries of mice, in rat renal AA and in
      pancreatic islet arterioles. RESULTS: Albumin (2 and 4% in the bath solution)
      significantly potentiated the contractile response of renal afferent arterioles
      induced by angiotensin II and adenosine, as well as their combination, compared
      to the control situation (0.1% albumin). Albumin did not influence the
      contractility of larger renal vessels or pancreatic islet arterioles. Mimicking
      the increase in the osmolality induced by 4% albumin by applying mannitol to the
      bath solution also increased the response of renal arterioles to Ang II. However,
      the effect was smaller compared to that of albumin. The nitric oxide
      bioavailability, measured by DAF-FM fluorescence, was reduced in afferent
      arterioles exposed to 4% albumin. CONCLUSION: The protein-induced modulation of
      AA tone is mediated by the increased osmolality as well as by NO scavenging. The
      results suggest a possible contribution of these mechanisms to the control of
      extracellular fluid volume via adjustment of renal blood flow and glomerular
      filtration rate.

PMID- 28748581
TI  - Coronary artery calcium may stabilize following islet cell transplantation in
      patients with type 1 diabetes.
AB  - Islet cell transplantation can functionally cure type 1 diabetes and also improve
      carotid intima-media thickness. This study provides a preliminary description of
      changes in coronary artery calcium following islet transplantation, and
      associated factors. Coronary artery calcium was measured in 14 patients with type
      1 diabetes (11 had measures both pre- and post-transplant [mean 2.3 years]) in
      the University of Illinois at Chicago's clinical trial. Multivariable mixed
      effects linear regression of repeated measures was used to quantify calcium
      change and determine if this change was longitudinally associated with
      risk/protective factors. Thirteen of the patients were female, with mean baseline
      age, diabetes duration, and BMI of 47.6 and 28.7 years, and 23.1, respectively.
      Over half (57%) had detectable coronary artery calcium pre-transplant. Minimal
      change (0.39 mm3 /y, P = .02) occurred in coronary artery calcium levels pre- to
      post-transplant. No patient met criteria for calcium progression. Coronary artery
      calcium was positively associated with total and small VLDL particles (P <= .02),
      statin dose (P = .02), and urine albumin-to-creatinine ratio (P = .04) and
      negatively associated with free fatty acids (P = .03), total HDL (P = .03), large
      HDL particles (P = .005), and tacrolimus dose (P = .02). Islet transplant may
      stabilize coronary artery calcium, with optimal management of lipids and kidney
      function remaining key therapeutic targets. [NCT00679041].

PMID- 28748583
TI  - Overall and abortion-related maternal mortality rates in Uruguay over the past 25
      years and their association with policies and actions aimed at protecting women's
      rights.
AB  - OBJECTIVE: To evaluate changes in maternal mortality rates in Uruguay over the
      past 25 years, as well as their distribution by cause, and their temporal
      relationship with social changes and Human Development Index (HDI) indicators.
      METHODS: Data on maternal mortality obtained directly from the Uruguayan Ministry
      of Public Health for the 2001 to 2015 period were analyzed together with data
      from the United Nations Inter-Agency Group for Child Mortality Estimation for the
      1990 to 2015 period. The swiftness of the decrease in maternal mortality per five
      year period, the variation in the percentage of abortion-related deaths, and the
      correlation with HDI indicators were evaluated. RESULTS: Maternal mortality
      decreased significantly, basically due to a reduction in the number of deaths
      from unsafe abortion, which was the principal cause of maternal mortality in the
      1990s. The reduction in maternal mortality over the past 10 years also coincides
      with a reduction in poverty and an improvement in the HDI. CONCLUSION: A rapid
      reduction occurred in maternal mortality in Uruguay, particularly in maternal
      mortality resulting from unsafe abortion. This coincided with the application of
      a model for reducing the risk and harm of unsafe abortions, which finally led to
      the decriminalization of abortion.

PMID- 28748584
TI  - A replication of the Uruguayan model in the province of Buenos Aires, Argentina,
      as a public policy for reducing abortion-related maternal mortality.
AB  - OBJECTIVE: To describe the application of the risk and harm reduction model at
      primary care level to decrease the mortality due to unsafe abortion in the
      Province of Buenos Aires, Argentina, and evaluate the results. METHODS: The
      services offered at primary health units to women undergoing abortion are
      described-first, only risk reduction and later, legal termination of the
      pregnancy-including their evolution between 2010 and 2015. The changes in
      abortion-related maternal mortality are also evaluated. The chi2 test was used to
      evaluate the differences in the percentage of abortion-related deaths out of the
      total number of maternal deaths. RESULTS: Primary care services increased
      progressively, both for risk reduction and for legal termination of pregnancy,
      which was carried out successfully, including manual vacuum aspiration, by
      general physicians and midwives. The proportion of abortion-related maternal
      deaths with respect to total maternal deaths fell by two-thirds between 2010 and
      2014 (P < 0.001). CONCLUSION: The Uruguayan risk reduction model was successfully
      applied in primary care in the Province of Buenos Aires.

PMID- 28748585
TI  - Evolution of adolescent fertility after decriminalization of abortion in
      Montevideo, Uruguay.
AB  - OBJECTIVE: To analyze the effect on adolescent fertility in Montevideo of the
      Uruguayan law on the voluntary termination of pregnancy that was passed in 2012.
      METHODS: The change in the number of births to teenage mothers between 2010 and
      2014 was analyzed, along with their characteristics before and after
      decriminalization of abortion. RESULTS: Descriptive analysis of abortion before
      and after decriminalization showed that there was no reduction, during the period
      analyzed, in adolescent fertility, nor any changes in the distribution of births.
      CONCLUSION: The normative change brought about by the law on the voluntary
      termination of pregnancy was not associated with any substantial change in the
      reproductive behavior of adolescents in Montevideo. We recommend that this
      analysis is taken further with impact evaluation methodologies.

PMID- 28748586
TI  - Legal termination of pregnancy as an opportunity for expanding postabortion
      contraception: Experience at the Pereira Rossell Hospital, Montevideo, Uruguay.
AB  - OBJECTIVE: To determine to what extent women adopted highly effective
      contraceptive methods after a legal abortion. METHODS: The data available during
      a period before and another period after liberalization of the abortion law were
      reviewed. The data gathering was incomplete and reliable only during certain
      periods, which were used in the study. RESULTS: There was an increase in the
      proportion of women who returned for contraception and in the proportion who used
      any method and long-acting methods; however, no contraception was administered
      immediately after abortion and only 16% of all women treated started to use a
      long-acting method during the period after the law was liberalized. CONCLUSION:
      The proposed objective was not being achieved, the recommended guidelines were
      not being followed, and data gathering was incomplete. Good intentions are not
      enough and it is always necessary to evaluate the performance of a program. The
      results indicate that immediate reforms are necessary in postabortion
      contraception services.

PMID- 28748587
TI  - From risk and harm reduction to decriminalizing abortion: The Uruguayan model for
      women's rights.
AB  - OBJECTIVE: To describe public policies, social actions, particularly those of
      obstetricians/gynecologists, and changes in abortion-related legislation in the
      different historical periods between 1990 and 2015, and to analyze temporal
      correlations with a reduction in maternal mortality. METHODS: The 1990-2015
      period was divided into three different stages to permit evaluation of the
      legislation, health regulations, healthcare system, and professional practices
      related to the care provided in cases of unsafe abortion: 1990-2001,
      characterized by illegality and the healthcare system's denial of abortion; 2001
      2012, when the model for reducing the risk and harm of unsafe abortions was
      developed; and 2012-2015, when abortion was finally decriminalized. RESULTS:
      Changes in public policies and expansion of the risk reduction model coincided
      with changes in the social perception of abortion and a decrease in maternal
      mortality and abortion rates, probably due to a set of public policies that led
      to the decriminalization of abortion in 2012. CONCLUSION: Changes in public
      policies and health actions such as the model for reducing the risk and harm of
      unsafe abortions coincided with a marked reduction in abortion-related maternal
      mortality. The challenges still to be faced include managing second trimester
      abortions, ensuring the creation of multidisciplinary teams, and offering
      postabortion contraception.

PMID- 28748588
TI  - Implementation of the risk and harm reduction strategy against unsafe abortion in
      Uruguay: From a university hospital to the entire country.
AB  - The history of the creation of the risk and harm reduction model applied to
      unsafe abortion is reviewed, from its initial implementation by a small group of
      gynecologists at the Pereira Rossell Hospital Center in Uruguay to its spread to
      the rest of the country. Its ethical rationale, its successful application in the
      hospital, the decision to disseminate it with the cooperation of the
      International Federation of Gynecology and Obstetrics (FIGO), and the
      intervention procedures are explained. It was evaluated from the epidemiological
      and anthropological viewpoints, from the changes in professionals' and users'
      perception of the care offered and its impact on complications and maternal
      deaths. A very favorable change was seen in the number and quality of the
      services, the providers' attitude, and maternal morbidity and mortality were
      reduced. It also brought visibility to women with unplanned and unwanted
      pregnancies and an improved understanding of their problems, which contributed to
      the legislative changes that were made subsequently.

PMID- 28748589
TI  - The role of medical abortion in the implementation of the law on voluntary
      termination of pregnancy in Uruguay.
AB  - OBJECTIVE: To evaluate the implementation of the law that liberalizes voluntary
      abortion in Uruguay and enables health services to offer these services to the
      population. METHODS: The legal and regulatory provisions are described and the
      national data-provided by the Ministry of Public Health's National Information
      System (SINADI)-on the number of voluntary terminations of pregnancy, the
      abortion method (medical or surgical), and whether it was performed as an
      outpatient or inpatient are analyzed. To determine complications, the number of
      maternal deaths and admissions to intensive care units for pregnant women was
      used. The study period ran from December 1, 2012, to December 31, 2014. RESULTS:
      A total of 15 996 abortions were performed during the study period; only 1.2%
      were surgical and 98.8% were medical. Of the latter, only 3.4% required
      hospitalization. Less than half of the pregnancies were terminated up to 9 weeks
      of gestation and 54% were at 10 to 12 weeks in a sample from the Pereira Rossell
      Hospital. CONCLUSION: The rapid nationwide rollout of voluntary termination of
      pregnancy services to all women was possible to a large degree thanks to the
      availability and broad acceptance of medical abortion, facilitated by the prior
      experience in applying the risk and harm reduction strategy.

PMID- 28748590
TI  - Conscientious objection as a barrier for implementing voluntary termination of
      pregnancy in Uruguay: Gynecologists' attitudes and behavior.
AB  - OBJECTIVE: To analyze the attitudes and behavior of gynecologists in Uruguay with
      respect to the right to conscientious objection that is included in the law
      concerning voluntary termination of pregnancy. METHODS: The relevant laws and
      decrees, academic articles, legal or administrative claims, and the positions
      published by the institutions representing physicians or by groups of
      gynecologists were analyzed. RESULTS: In general, the institutions positioned
      themselves in favor of correct application of conscientious objection and the
      immense majority of gynecologists followed this conduct. Small groups mounted a
      strong opposition and in one department (province) all gynecologists declared
      themselves to be objectors. CONCLUSION: Most gynecologists, whether or not they
      are objectors, proved to have a "loyalty to duty," fulfilling their primary
      obligation to abide by the ethical duty to give treatment to the persons who need
      it. A small group used conscientious objection to impede the provision of care to
      the women who needed the service, some group members being genuine objectors and
      others pseudo-objectors.

PMID- 28748591
TI  - What can we do as gynecologists/obstetricians to reduce unsafe abortion and its
      consequences? The Uruguayan response.

PMID- 28748592
TI  - Influence of narrowband ultraviolet B phototherapy on serum tumour necrosis
      factor-like weak inducer of apoptosis (TWEAK) in patients with psoriasis.
AB  - Psoriasis is characterized by keratinocyte resistance to apoptosis. We recently
      demonstrated an increase in serum tumour necrosis factor-like weak inducer of
      apoptosis (TWEAK) in patients after topical treatment for psoriasis. We decided
      to verify whether narrowband ultraviolet B (NB-UVB) has a similar effect. Serum
      concentration of TWEAK was estimated in patients with exacerbated plaque
      psoriasis treated with NB-UVB. Baseline TWEAK levels were similar in patients
      with psoriasis and healthy controls, and Psoriasis Area and Severity Index (PASI)
      correlated inversely with TWEAK levels. Treatment with NB-UVB caused a
      significant reduction in PASI and concurrent increase in serum TWEAK. This
      finding may be due to increased expression of TWEAK receptor in psoriatic skin,
      which has been reported previously, with consequent binding of excess soluble
      TWEAK during treatment and subsequent release after treatment. Severity of plaque
      psoriasis and its improvement after NB-UVB treatment may be associated with TWEAK
      concentrations. The importance of our findings remains to be established.

PMID- 28748593
TI  - The use of life review to enhance spiritual well-being in patients with terminal
      illnesses: An integrative review.
AB  - AIMS AND OBJECTIVES: To conduct an integrative review of the current literature
      on using life review as an intervention to address the spiritual need of patients
      with terminal illnesses. BACKGROUND: Palliative care highlights the holistic
      approach of care including the spiritual aspect. Life review has been used in
      palliative nursing intending to enhance patients' emotional and spiritual well
      being, and quality of life. However, there is a lack of publications that provide
      a structured overview on life review programmes and their effectiveness. DESIGN:
      Integrative review. METHODS: The Whittemore and Knafl integrative review method
      was used. Five major online databases were included in our literature search. The
      keywords used were "life review" and "palliative care, terminal care, terminally
      ill, death & dying, hospice, spiritual wellbeing, spirituality". Seven primary
      papers were identified, critically appraised and synthesised in the final review.
      RESULTS: There are limited clinical studies on life review programmes for
      patients with terminal illness. The research design of these studies is too
      widely varied for meta-analysis. Here, we identified two major programmes of life
      review as an intervention to address the spiritual well-being of patients with
      terminal illness. However, repeated studies on the effectiveness of these two
      programmes are lacking. The shorter programme of life review is more likely to be
      applicable and effective for terminal patients. CONCLUSIONS: Further research in
      this area is required to provide strong evidence on the effectiveness and
      applicability of life review in patients receiving palliative care. RELEVANCE TO
      CLINICAL NURSING: This review adds weight to the need of a better understanding
      on the use of life review in addressing the spiritual needs of patients with
      terminal illness. Such understanding would provide evidence for the use of life
      review as an alternative approach in palliative care delivery.

PMID- 28748594
TI  - Spanish validation of the PAS-ADD Checklist Questionnaire for people with
      intellectual disabilities for Spanish population.
AB  - BACKGROUND: The Psychiatric Assessment Schedule for Adult with Developmental
      Disability (PAS-ADD) is an international reference tool for the diagnosis and
      assessment of mental health problems and behavioural disorders among people with
      intellectual disabilities. Although the original PAS-ADD instrument has been
      validated in the Spanish language, the shorter PAS-ADD Checklist has yet not been
      validated. The aim of this study is to validate the PAS-ADD Checklist for the
      Spanish population. METHODS: The PAS-ADD Checklist Questionnaire was administered
      to 208 adults with intellectual disabilities at a vocational centre in Madrid,
      Spain. The psychometric analyses included internal consistency, inter-rater and
      test-retest reliability, Varimax rotation factor analysis for construct validity,
      criterion validity and feasibility. RESULTS: The Cronbach's alpha was 0.80 for
      the overall questionnaire and between 0.40 and 0.79 for the subscales. The Kappa
      coefficients for test-retest and inter-rater reliability were between 0.66 and
      0.80. Varimax rotation factor analysis showed five well-defined factors. The
      Kappa coefficients for criterion validity were between 0.30 and 0.70. Feasibility
      was also good. CONCLUSIONS: The PAS-ADD Checklist is a feasible and reliable
      instrument for carrying out initial assessment of the mental health status of
      adults with intellectual disabilities, referring cases to more specialised
      diagnosis and treatment.

PMID- 28748595
TI  - Genes important for survival or reproduction in Varroa destructor identified by
      RNAi.
AB  - The Varroa mite, (Varroa destructor), is the worst threat to honey bee health
      worldwide. To explore the possibility of using RNA interference to control this
      pest, we determined the effects of knocking down various genes on Varroa mite
      survival and reproduction. Double-stranded RNA (dsRNA) of six candidate genes
      (Da, Pros26S, RpL8, RpL11, RpP0 and RpS13) were synthesized and each injected
      into Varroa mites, then mite survival and reproduction were assessed. Injection
      of dsRNA for Da (Daughterless) and Pros26S (Gene for proteasome 26S subunit
      adenosine triphosphatase) caused a significant reduction in mite survival, with
      3.57% +/- 1.94% and 30.03% +/- 11.43% mites surviving at 72 h post-injection
      (hpi), respectively. Control mites injected with green fluorescent protein (GFP)
      dsRNA showed survival rates of 81.95% +/- 5.03% and 82.36 +/- 2.81%,
      respectively. Injections of dsRNA for four other genes (RpL8, RpL11, RpP0 and
      RpS13) did not affect survival significantly, enabling us to assess their effect
      on Varroa mite reproduction. The number of female offspring per mite was
      significantly reduced for mites injected with dsRNA of each of these four genes
      compared to their GFP-dsRNA controls. Knockdown of the target genes was verified
      by real-time polymerase chain reaction for two genes important for reproduction
      (RpL8, RpL11) and one gene important for survival (Pros26S). In conclusion,
      through RNA interference, we have discovered two genes important for mite
      survival and four genes important for mite reproduction. These genes could be
      explored as possible targets for the control of Varroa destructor in the future.

PMID- 28748597
TI  - Communication in pediatric oncology: State of the field and research agenda.
AB  - From the time of diagnosis through either survivorship or end of life,
      communication between healthcare providers and patients or parents can serve
      several core functions, including fostering healing relationships, exchanging
      information, responding to emotions, managing uncertainty, making decisions, and
      enabling patient/family self-management. We systematically reviewed all studies
      that focused on communication between clinicians and patients or parents in
      pediatric oncology, categorizing studies based on which core functions of
      communication they addressed. After identifying gaps in the literature, we
      propose a research agenda to further the field.

PMID- 28748596
TI  - Concise Review: Stem Cells for Corneal Wound Healing.
AB  - Corneal wound healing is a complex process that occurs in response to various
      injuries and commonly used refractive surgery. It is a significant clinical
      problem, which may lead to serious complications due to either incomplete
      (epithelial) or excessive (stromal) healing. Epithelial stem cells clearly play a
      role in this process, whereas the contribution of stromal and endothelial
      progenitors is less well studied. The available evidence on stem cell
      participation in corneal wound healing is reviewed, together with the data on the
      use of corneal and non-corneal stem cells to facilitate this process in diseased
      or postsurgical conditions. Important aspects of corneal stem cell generation
      from alternative cell sources, including pluripotent stem cells, for possible
      transplantation upon corneal injuries or in disease conditions are also
      presented. Stem Cells 2017;35:2105-2114.

PMID- 28748598
TI  - An evaluation of the effectiveness of psychological therapy in reducing general
      psychological distress for adults with autism spectrum conditions and comorbid
      mental health problems.
AB  - OBJECTIVE: To investigate the effectiveness of psychological therapy in reducing
      psychological distress for adults with autism spectrum conditions (ASC) and co
      morbid mental health conditions in routine clinical practice. To explore the
      effect of individual characteristics and service factors on change in general
      distress. METHOD: In a specialist psychological therapies service for adults with
      ASC, the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) self
      report questionnaire of psychological distress is completed by clients at start
      and end of therapy. Change over time and reliable and clinical change was
      assessed for 81 of a total of 122 clients (66.4%). Factors which may influence
      change over time were explored using available clinical information. RESULTS:
      Overall, there was a significant reduction in CORE-OM score during therapy with a
      small effect size. Most clients showed an improvement in psychological distress
      over therapy (75.4% improved, with 36.9% of these showing reliable changes).
      Significant and comparable reductions from pre-therapy to post-therapy were seen
      across the sample, showing that individual differences did not mediate therapy
      effectiveness. CORE-OM scores mediate the association between age of ASD
      diagnosis and hours of therapeutic input required, with greater age at diagnosis
      and higher distress associated with longer therapy duration. CONCLUSIONS: Our
      preliminary findings suggest that psychological therapy may be effective in
      reducing general distress for clients with ASC and co-morbid mental health
      conditions and should be routinely offered. Individuals who are diagnosed with
      ASD in adulthood are likely to require a longer course of therapy when their
      general distress scores are high.

PMID- 28748599
TI  - A comparison of statistical methods for the study of etiologic heterogeneity.
AB  - Cancer epidemiologic research has traditionally been guided by the premise that
      certain diseases share an underlying etiology, or cause. However, with the rise
      of molecular and genomic profiling, attention has increasingly focused on
      identifying subtypes of disease. As subtypes are identified, it is natural to ask
      the question of whether they share a common etiology or in fact arise from
      distinct sets of risk factors. In this context, epidemiologic questions of
      interest include (1) whether a risk factor of interest has the same effect across
      all subtypes of disease and (2) whether risk factor effects differ across levels
      of each individual tumor marker of which the subtypes are comprised. A number of
      statistical models have been proposed to address these questions. In an effort to
      determine the similarities and differences among the proposed methods, and to
      identify any advantages or disadvantages, we use a simplified data example to
      elucidate the interpretation of model parameters and available hypothesis tests,
      and we perform a simulation study to assess bias in effect size, type I error,
      and power. The results show that when the number of tumor markers is small enough
      that the cross-classification of markers can be evaluated in the traditional
      polytomous logistic regression framework, then the statistical properties are at
      least as good as the more complex modeling approaches that have been proposed.
      The potential advantage of more complex methods is in the ability to accommodate
      multiple tumor markers in a model of reduced parametric dimension.

PMID- 28748600
TI  - Accuracy and confidence of allied health assistants administering the subjective
      global assessment on inpatients in a rural setting: a preliminary feasibility
      study.
AB  - AIM: Malnutrition has a significant impact on patient outcomes and duration of
      inpatient stay. However, conducting timely nutrition assessments can be
      challenging for rural dietitians. A solution could be for allied health
      assistants (AHAs) to assist with these assessments. The present study aimed to
      assess the accuracy and confidence of AHAs trained to conduct the subjective
      global assessment (SGA) compared with dietitians. METHODS: A non-inferiority
      study design was adopted. Forty-five adult inpatients admitted to a rural and
      remote health service were assessed independently by both a trained AHA and
      dietitian within 24 hours. The order of assessment was randomised, with the
      second assessor blind to the outcome of the initial SGA. Levels of agreement were
      examined using kappa and percent exact agreement (PEA; set a priori at >=80%).
      Rater confidence after each assessment was assessed using a 10-point scale.
      RESULTS: Agreement for overall SGA ratings was high (kappa = 0.84; PEA 84.4%).
      PEA for individual sub-components of the SGA ranged from 66.4 to 86.7%. Where
      discrepancies were identified in global SGA ratings, AHAs provided a more severe
      rating of malnutrition than dietitians. AHAs reported significantly lower
      confidence than dietitians (t = 4.49, P < 0.001), although mean confidence for
      both groups was quite high (AHA=7.5, dietitians = 9.0). CONCLUSIONS: Trained AHAs
      completed the SGA with similar accuracy to dietitians. Using AHAs may help
      facilitate timely nutrition assessment in rural health services when a dietitian
      is not physically present. Further investigation is required to determine the
      benefits of incorporating this extended role into rural and remote health-care
      services.

PMID- 28748601
TI  - Substrate specificity in the context of molecular chaperones.
AB  - Molecular chaperones are one of the key players in protein biology and as such
      their structure and mechanism of action have been extensively studied. However
      the substrate specificity of molecular chaperones has not been well investigated.
      This review aims to summarize what is known about the substrate specificity and
      substrate recognition motifs of chaperones so as to better understand what
      substrate specificity means in the context of molecular chaperones. Available
      literature shows that the majority of chaperones have broad substrate range and
      recognize non-native conformations of proteins depending on recognition of
      hydrophobic and/or charged patches. Based on these recognition motifs chaperones
      can select for early, mid or late folding intermediates. Another major
      contributor to chaperone specificity are the co-chaperones they interact with as
      well as the sub-cellular location they are expressed in and the inducability of
      their expression. Some chaperones which have only one or a few known substrates
      are reported. In their case the mode of recognition seems to be specific
      structural complementarity between chaperone and substrate. It can be concluded
      that the vast majority of chaperones do not show a high degree of specificity but
      recognize elements that signal non-native protein conformation and their
      substrate range is modulated by the context they function in. However a few
      chaperones are known that display exquisite specificity of their substrate e.g.
      mammalian heat shock protein 47 collagen interaction. (c) 2017 IUBMB Life,
      69(9):647-659, 2017.

PMID- 28748603
TI  - Graphene Quantum Dots Downregulate Multiple Multidrug-Resistant Genes via
      Interacting with Their C-Rich Promoters.
AB  - Multidrug resistance (MDR) is the major factor in the failure of many forms of
      chemotherapy, mostly due to the increased efflux of anticancer drugs that
      mediated by ATP-binding cassette (ABC) transporters. Therefore, inhibiting ABC
      transporters is one of effective methods of overcoming MDR. However, high
      enrichment of ABC transporters in cells and their broad substrate spectra made to
      circumvent MDR are almost insurmountable by a single specific ABC transporter
      inhibitor. Here, this study demonstrates that graphene quantum dots (GQDs) could
      downregulate the expressions of P-glycoprotein, multidrug resistance protein
      MRP1, and breast cancer resistance protein genes via interacting with C-rich
      regions of their promoters. This is the first example that a single reagent could
      suppress multiple MDR genes, suggesting that it will be possible to target
      multiple ABC transporters simultaneously with a single reagent. The inhibitory
      ability of the GQDs to these drug-resistant genes is validated further by
      reversing the doxorubicin resistance of MCF-7/ADR cells. Notably, GQDs have
      superb chemical and physical properties, unique structure, low toxicity, and high
      biocompatibility; hence, their capability of inhibiting multiple drug-resistant
      genes holds great potential in cancer therapy.

PMID- 28748602
TI  - VIncristine, irinotecan, and temozolomide in children and adolescents with
      relapsed rhabdomyosarcoma.
AB  - BACKGROUND: The combination of vincristine, irinotecan, and temozolomide (VIT) is
      often used to treat children and adolescents with relapsed rhabdomyosarcoma
      (RMS); however, the outcome of these patients has not been previously described.
      PROCEDURES: We sought to determine the response rate (RR) and progression-free
      survival (PFS) for patients with relapsed RMS treated with VIT by retrospective
      review of patients treated at five tertiary care hospitals. Prior treatment with
      irinotecan was permitted. RESULTS: Among 19 patients with a median age of 8 years
      (range 2-17 years), 12 (63%) were males and 12 (63%) had embryonal histology.
      Median time to relapse from initial diagnosis was 16 months (range 2.8-45
      months). VIT was used as first, second, third, or fourth line of therapy in four
      (21%), seven (37%), six (32%), and two (10%) patients, respectively. Four
      patients received VIT as adjuvant therapy following radiation and/or surgery.
      Therefore, among 15 evaluable patients, the best response to VIT was 0 (complete
      response, CR), 0 (partial response, PR), 4 (stable disease, SD), and 11
      (progressive disease, PD) for an overall clinical benefit rate (CR + PR + SD) of
      26.7% (95% CI: 7.8-55.1%). After a median follow-up of 8 months, 2 (10%) patients
      were alive without disease, 3 (16%) were alive with disease, and 14 (74%)
      patients died of PD. PFS at 3 months was 23% (95% CI: 5.7-46.7%). CONCLUSIONS:
      VIT therapy in combination with adequate local control is associated with some
      disease control in patients with first relapse RMS and may be another reasonable
      option to offer patients as salvage therapy.

PMID- 28748604
TI  - Implementing pharmacogenomics in modern health care: The 2017 scientific meeting
      of the Human Genome Variation Society.

PMID- 28748605
TI  - Management of chemotherapy-induced febrile neutropenia in pediatric oncology
      patients: A North American survey of pediatric hematology/oncology and pediatric
      infectious disease physicians.
AB  - BACKGROUND: Chemotherapy-induced febrile neutropenia (FN) is traditionally
      managed with hospital admission for parenteral antibiotics until neutropenia
      resolves. Recent studies have explored risk stratification and the safety of
      managing "low-risk" patients as outpatients. Few studies have directly assessed
      pediatric provider preferences for managing FN. PROCEDURE: We conducted a survey
      of practicing US and Canadian pediatric hematology/oncology (PHO) and pediatric
      infectious disease (PID) physicians to assess their FN management preferences
      using case scenarios with varying risk profiles. RESULTS: Twenty-one percent (n =
      186) of PHO and 32% (n = 123) of PID physicians completed the survey. Overall,
      both groups of providers agreed regarding which patients with FN could be managed
      outpatient. For a child with acute lymphoblastic leukemia receiving maintenance
      chemotherapy with an absolute neutrophil count (ANC) of 400 cells/MUl, 35% (n =
      66) of PHO and 49% (n = 60) of PID physicians would consider outpatient
      management (P = 0.02). Of those physicians selecting inpatient management, 41% (n
      = 49) of PHO and 52% (n = 33) of PID physicians would be willing to discharge the
      patient without an increase in ANC, if afebrile with a negative blood culture (P
      = 0.16). For a similar patient with an ANC of 100 cells/MUl, only 23% (n = 35) of
      PHO and 42% (n = 39) of PID physicians would consider discharge without an
      increase in ANC (P = 0.002). CONCLUSIONS: Despite the lack of established
      guidelines for low-risk pediatric FN, a significant proportion of North American
      physicians report willingness to modify traditional management. This reinforces
      the need for evidence-based low-risk criteria and outpatient management
      guidelines to optimize consistency of care for these patients.

PMID- 28748606
TI  - Reversible Interconversion between 2,5-Dimethylpyrazine and 2,5
      Dimethylpiperazine by Iridium-Catalyzed Hydrogenation/Dehydrogenation for
      Efficient Hydrogen Storage.
AB  - A new hydrogen storage system based on the hydrogenation and dehydrogenation of
      nitrogen heterocyclic compounds, employing a single iridium catalyst, has been
      developed. Efficient hydrogen storage using relatively small amounts of solvent
      compared with previous systems was achieved by this new system. Reversible
      transformations between 2,5-dimethylpyrazine and 2,5-dimethylpiperazine,
      accompanied by the uptake and release of three equivalents of hydrogen, could be
      repeated almost quantitatively at least four times without any loss of
      efficiency. Furthermore, hydrogen storage under solvent-free conditions was also
      accomplished.

PMID- 28748607
TI  - Simultaneous detection of zinc dimethyldithiocarbamate and zinc
      ethylenebisdithiocarbamate in cabbage leaves by capillary electrophoresis with
      inductively coupled plasma mass spectrometry.
AB  - We report a simple and highly sensitive method for the simultaneous detection of
      trace zinc dimethyldithiocarbamate and zinc ethylenebisdithiocarbamate by
      capillary electrophoresis with inductively coupled plasma mass spectrometry. Zinc
      dimethyldithiocarbamate and zinc ethylenebisdithiocarbamate were chelated with
      trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid to form a macromolecule
      complex. Then, these two compounds were separated by alpha-cyclodextrin-modified
      capillary electrophoresis within 12 min at a separation voltage of 15 kV and
      measured by inductively coupled plasma mass spectrometry. The developed method is
      sensitive with detection limit of 1.9 and 3.0 ng Zn/mL for zinc
      dimethyldithiocarbamate and zinc ethylenebisdithiocarbamate, respectively. By
      means of ultrasound-assisted extraction methods, zinc dimethyldithiocarbamate and
      zinc ethylenebisdithiocarbamate spiked into cabbage leaves were successfully
      extracted and determined with a relative standard deviation (n = 5) <= 6% and a
      recovery of 95-107%.

PMID- 28748608
TI  - Four years comparative follow-up evaluation of community-based, step-down, and
      residential specialist psychodynamic programmes for personality disorders.
AB  - Although the fulcrum of service provision for personality disorder (PD) has
      shifted from hospital-based to psychodynamically- and cognitively-oriented
      outpatient programmes, very few studies have attempted to compare specialist
      moderate intensity outpatient programmes with specialist high-intensity
      residential models, or to explore whether a period of inpatient treatment may be
      necessary to improve outcome and prognosis. In this article, we prospectively
      compare changes over a 4-year period in 3 groups of patients with personality
      disorders (N = 162) treated in a specialist community-based (CBP, N = 30), a step
      down (RT-CBP, N = 87), and a specialist residential programme (RT, N = 45) in
      psychiatric distress, deliberate self-injury, and suicide attempt using
      multilevel modelling and multivariate logistic regression analyses. The results
      showed that percentages of early-dropout were significantly different (p = .0001)
      for the 3 programmes (CBP = 13.4%, RT-CBP = 10.2%, and RT = 41.4%). A significant
      interaction between treatment model and time was found for psychiatric distress
      (p = .001), with CBP and RT-CBP achieving more marked changes (g = 1.20 and g =
      0.68, respectively) compared to RT (g = 0.30) at 48-month follow-up. CBP and RT
      CBP were found to significantly reduce impulsive behaviour (deliberate self
      injury and suicide attempt) compared to RT. Severity of presentation was not
      found to be a significant predictor of outcome. Long-term RT showed no advantage
      over long-term CBP, either as stand-alone or as step-down treatment. Replication
      may be needed to confirm generalizability of results, and a number of limitations
      in the study design may moderate the inferences that can be drawn from the
      results.

PMID- 28748609
TI  - Effectiveness of surgical treatment of severe macrocheilia in a patient with
      orofacial granulomatosis.
AB  - Orofacial granulomatosis (OFG) is the term given to a group of diseases
      characterized by the presence of non-necrotizing granulomatous inflammation
      affecting the soft tissues of the orofacial region. Treatment of OFG is often
      challenging and unsatisfactory. We report on a 32-year-old man with a 2-year
      history of oedema and swelling of the upper lip without systemic symptoms. The
      history, clinical features and histopathological findings led to the diagnosis of
      cheilitis granulomatosa (CG), a disease included in the spectrum of OFG. The
      patient was treated with oral diaminodiphenyl sulfone (DDS) and clofazimine
      without success. Oral doxycycline led to a slight improvement of the disease.
      Because the volume of the upper lip was twice normal size, surgical reduction was
      performed, followed by administration of oral doxycycline for 3 months. This
      therapeutic approach led to complete remission, with no recurrence after 3 years.

PMID- 28748610
TI  - Using family and staff experiences of a botulinum toxin-A service to improve
      service quality.
AB  - BACKGROUND: The decision for families to proceed with botulinum toxin-A (BoNT-A)
      injections for managing childhood conditions involving hypertonia can be complex.
      Family-centred care is a service model that facilitates supporting families in
      this decision-making process. Understanding families' experiences of services is
      critical to developing family-centred care. The aim of this project was therefore
      to increase understanding of the experiences of families of children attending a
      BoNT-A service in order to improve the service and its family-centred approach to
      care. METHOD: Sixteen staff of a BoNT-A service participated in a patient journey
      mapping exercise. Nine families of the service participated in in-depth
      interviews. Interviews were audio-recorded and transcribed verbatim. Data from
      the staff session and interviews were analysed independently using grounded,
      hermeneutic thematic analysis. RESULTS: Staff sessions revealed 5 core themes
      that related to impacting on the family experience. Family interviews revealed 4
      core themes, with 7 subthemes and 1 latent theme. CONCLUSIONS: Areas of
      importance identified by families relating to BoNT-A treatment included
      acknowledgement of individual needs, care coordination, empowerment of families
      and patients, consistency in service delivery, and the distressing nature of
      appointment and decision-making. Comparison of the data from the staff patient
      journey mapping and family interviews suggested that staff have a good but
      incomplete understanding of the factors important to families, highlighting the
      need for consumer engagement in establishing family-centred care. The themes
      identified can guide the provision of family-centred BoNT-A injection clinics.

PMID- 28748611
TI  - Apelin-induced cardioprotection against ischaemia/reperfusion injury: roles of
      epidermal growth factor and Src.
AB  - AIM: Apelin, the ligand of the G-protein-coupled receptor (GPCR) APJ, exerts a
      post-conditioning-like protection against ischaemia/reperfusion injury through
      activation of PI3K-Akt-NO signalling. The pathway connecting APJ to PI3K is still
      unknown. As other GPCR ligands act through transactivation of epidermal growth
      factor receptor (EGFR) via a matrix metalloproteinase (MMP) or Src kinase, we
      investigated whether EGFR transactivation is involved in the following three
      features of apelin-induced cardioprotection: limitation of infarct size,
      suppression of contracture and improvement of post-ischaemic contractile
      recovery. METHOD: Isolated rat hearts underwent 30 min of global ischaemia and 2
      h of reperfusion. Apelin (0.5 MUm) was infused during the first 20 min of
      reperfusion. EGFR, MMP or Src was inhibited to study the pathway connecting APJ
      to PI3K. Key components of RISK pathway, namely PI3K, guanylyl cyclase or
      mitochondrial K+ -ATP channels, were also inhibited. Apelin-induced EGFR and
      phosphatase and tensing homolog (PTEN) phosphorylation were assessed. Left
      ventricular pressure and infarct size were measured. RESULTS: Apelin-induced
      reductions in infarct size and myocardial contracture were prevented by the
      inhibition of EGFR, Src, MMP or RISK pathway. The involvement of EGFR was
      confirmed by its phosphorylation. However, neither direct EGFR nor MMP inhibition
      affected apelin-induced improvement of early post-ischaemic contractile recovery,
      which was suppressed by Src and RISK inhibitors only. Apelin also increased PTEN
      phosphorylation, which was removed by Src inhibition. CONCLUSION: While EGFR and
      MMP limit infarct size and contracture, Src or RISK pathway inhibition suppresses
      the three features of cardioprotection. Src does not only transactivate EGFR, but
      also inhibits PTEN by phosphorylation thus playing a crucial role in apelin
      induced cardioprotection.

PMID- 28748612
TI  - Sol-gel-adsorbent-coated extraction needles to detect volatile compounds in
      spoiled fish.
AB  - Volatile compounds generated by fish spoilage were investigated by an inside
      needle microextraction method followed by gas chromatography with flame
      ionization detection and gas chromatography with mass spectrometry. The inside of
      a needle was coated with an adsorbent to extract the target analytes from the
      headspace of the sample. The examined adsorbents included beta-cyclodextrin,
      polystyrene resin cross-linked with 1% divinylbenzene, and polyethylene glycol
      mixed with polydimethylsiloxane. The investigated volatile compounds generated by
      fish spoilage were acetone, 2-butanone, 2-butanol, 2-propanol, dimethyl
      disulfide, acetic acid, and benzaldehyde. The analysis conditions for the
      sorption and desorption processes were optimized. Each optimized condition was
      validated by determining the limit of detection and the limit of quantitation
      from the calibration curves, as well as the recovery, reproducibility, and
      concentration factors. As a result, all of the fabricated needles afforded
      successful recoveries, above 90%, with relative standard deviations below 10%. In
      particular, cyclodextrin and polystyrene resin cross-linked with 1%
      divinylbenzene mixed with polydimethylsiloxane show good sensitivities and
      concentration factors for the standard volatile compounds. The storage of fresh
      mackerel and salted mackerel at room temperature for 14 days caused the
      concentrations of dimethyl disulfide and acetic acid to significantly increase
      while those of acetone, 2-butanone, 2-propanol, and 2-butanol changed only
      slightly.

PMID- 28748613
TI  - A rapid method for the determination of brominated flame retardant concentrations
      in plastics and textiles entering the waste stream.
AB  - Due to new European legislation, products going to waste are subject to 'low
      persistent organic pollutant concentration limits'. Concentrations of restricted
      brominated flame retardants in waste products must be determined. A rapid
      extraction and clean-up method was developed for determination of brominated
      flame retardants in various plastics and textiles. The optimised method used
      vortexing and ultrasonication in dichloromethane followed by sulfuric acid clean
      up to determine target compounds. Poly-brominated diphenyl ethers were determined
      by gas chromatography with mass spectrometry and hexabromocyclododecane by liquid
      chromatography with tandem mass spectrometry. Good recoveries of target analytes
      were obtained after three extraction cycles. The method was validated using poly
      propylene and poly-ethylene certified reference materials as well as previously
      characterised textiles, expanded and extruded poly-styrene samples. Measured
      concentrations of target compounds showed good agreement with the certified
      values indicating good accuracy and precision. Clean extracts provided low noise
      levels resulting in low limits of quantification (0.8-1.5 ng/g for poly
      brominated diphenyl ethers and 0.3 ng/g for alpha-, beta- and gamma
      hexabromocyclododecane). The developed method was applied successfully to real
      consumer products entering the waste stream and it provided various advantages
      over traditional methods, including reduced analysis time, solvent consumption,
      minimal sample contamination and high sample throughput, which is crucial to
      comply with the implemented legislation.

PMID- 28748615
TI  - Burying beetles regulate the microbiome of carcasses and use it to transmit a
      core microbiota to their offspring.
AB  - Necrophagous beetles utilize carrion, a highly nutritious resource that is
      susceptible to intense microbial competition, by treating it with antimicrobial
      anal and oral secretions. However, how this regulates the carcass microbiota
      remains unclear. Here, we show that carcasses prepared by the burying beetle
      Nicrophorus vespilloides undergo significant changes in their microbial
      communities subsequent to their burial and "preparation." Prepared carcasses
      hosted a microbial community that was more similar to that of beetles' anal and
      oral secretions than to the native carcass community or the surrounding soil,
      indicating that the beetles regulated the carcass microbiota. A core microbial
      community (Xanthomonadaceae, Enterococcaceae, Enterobacteriaceae and Yarrowia
      yeasts) was transmitted by the beetles to the larvae via the anal and oral
      secretions and the carcass surface. These core taxa proliferated on the carcass,
      indicating a growth conducive environment for these microbes when associated with
      beetles. However, total bacterial loads were higher on decomposing carcasses
      without beetles than on beetle-prepared carcasses, indicating that the beetles
      and/or their associated symbionts suppress the growth of competing microbes.
      Thus, apart from being a nutritional resource, the carcass provides a medium for
      vertical transmission of a tightly regulated symbiotic microbiota, whose activity
      on the carcass and in the larval gut may involve carcass preservation as well as
      digestion.

PMID- 28748614
TI  - Novel activating BRAF fusion identifies a recurrent alternative mechanism for ERK
      activation in pediatric Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm
      characterized by constitutive activation of extracellular signal-regulated kinase
      (ERK). Genomic characterization has identified activating point mutations
      including mutually exclusive BRAFV600E and activating MAP2K1 mutations to be
      responsible for ERK activation in a majority of pediatric LCH patients. Here, we
      report the discovery of a novel BRAF kinase fusion, PACSIN2-BRAF, in a child with
      multisystem LCH. This is the second reported case of an activating BRAF kinase
      fusion and indicates a recurrent pathologic mechanism. Genomic evaluation for
      activating kinase fusions should be strongly considered in pediatric LCH patients
      lacking more common mutations.

PMID- 28748616
TI  - Corrigendum: A Highly Active Manganese Catalyst for Enantioselective Ketone and
      Ester Hydrogenation.

PMID- 28748617
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 32/2017.

PMID- 28748618
TI  - Corrigendum: Localized Chemical Remodeling for Live Cell Imaging of Protein
      Specific Glycoform.

PMID- 28748619
TI  - Corrigendum: The Interstitial Carbon of the Nitrogenase FeMo Cofactor is Far
      Better Stabilized than Previously Assumed.

PMID- 28748620
TI  - Corrigendum: Pyridylidene-Mediated Dihydrogen Activation Coupled with Catalytic
      Imine Reduction.

PMID- 28748621
TI  - Outcomes of matched sibling donor bone marrow transplantation in children using
      single-agent calcineurin inhibitors as prophylaxis for graft versus host disease.
AB  - BACKGROUND: Optimal graft versus host disease (GVHD) prophylaxis prevents severe
      manifestations without excess immunosuppression. Standard prophylaxis includes a
      calcineurin inhibitor (CNI) with low-dose methotrexate. However, single-agent CNI
      may be sufficient prophylaxis for a defined group of patients. Single-agent CNI
      has been used for GVHD prophylaxis for human leukocyte antigen (HLA)-matched
      sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the
      Children's Hospital of Philadelphia for over 20 years. Here, we describe outcomes
      using this prophylactic strategy in a recent cohort. PROCEDURE: We performed a
      single-institution chart review and retrospective analysis of consecutive
      children undergoing MSD BMT who received single-agent CNI for GVHD prophylaxis
      between January 2002 and December 2014. RESULTS: Fifty-two children with a median
      age of 6.1 years (interquartile range [IQR] 2.5-8.3) and donor age of 6 years
      (IQR 3-10), with malignant and nonmalignant diseases (n = 35 and 17,
      respectively) were evaluated. Forty-three (82.6%) received oral prophylaxis with
      single-agent tacrolimus after initial intravenous therapy. Rates of GVHD were
      consistent with reported rates on dual prophylaxis: the overall incidence of
      grades 2-4 acute GVHD was 25.5%, grades 3-4 GVHD 9.8%, and chronic GVHD 10.4%.
      The cumulative incidence of relapse among children with malignancy was 20% at a
      median of 237 days (IQR 194-318) post-transplant. Two-year overall survival was
      82.7% (95% confidence interval [CI]: 69.4-90.6%) and event-free survival was
      78.9% (95% CI: 65.1-87.7%). No patient experienced graft failure. CONCLUSIONS:
      Single-agent CNI is a safe, effective approach to GVHD prophylaxis in young
      patients undergoing HLA-identical sibling BMT. Additionally, single-agent oral
      tacrolimus is a reasonable alternative to cyclosporine in this population.

PMID- 28748622
TI  - Behind your very eyes: a response to Kok and Jarodzka.

PMID- 28748623
TI  - Photoacoustic-Guided Surgery with Indocyanine Green-Coated Superparamagnetic Iron
      Oxide Nanoparticle Clusters.
AB  - A common cause of local tumor recurrence in brain tumor surgery results from
      incomplete surgical resection. Adjunctive technologies meant to facilitate gross
      total resection have had limited efficacy to date. Contrast agents used to
      delineate tumors preoperatively cannot be easily or accurately used in the real
      time operative setting. Although multimodal imaging contrast agents are developed
      to help the surgeon discern tumor from normal tissue in the operating room, these
      contrast agents are not readily translatable. This study has developed a novel
      contrast agent comprised solely of two Food and Drug Administration approved
      components, indocyanine green (ICG) and superparamagnetic iron oxide (SPIO)
      nanoparticles-with no additional amphiphiles or carrier materials, to enable
      preoperative detection by magnetic resonance (MR) imaging and intraoperative
      photoacoustic (PA) imaging. The encapsulation efficiency of both ICG and SPIO
      within the formulated clusters is ~100%, and the total ICG payload is 20-30% of
      the total weight (ICG + SPIO). The ICG-SPIO clusters are stable in physiologic
      conditions; can be taken up within tumors by enhanced permeability and retention;
      and are detectable by MR. In a preclinical surgical resection model in mice,
      following injection of ICG-SPIO clusters, animals undergoing PA-guided surgery
      demonstrate increased progression-free survival compared to animals undergoing
      microscopic surgery.

PMID- 28748624
TI  - The relationship between coping style and psychological distress in people with
      head and neck cancer: A systematic review.
AB  - OBJECTIVE: Individuals diagnosed with head and neck cancer (HNC) are at elevated
      risk of psychological distress and reduced quality of life. This review aimed to
      systematically examine and critically assess the quality of empirical evidence
      for associations between coping mechanisms and psychological distress among
      people with HNC. METHODS: CINAHL, MEDLINE, PsycINFO, EMBASE, and Web of Science
      were searched. Studies were included if they used reliable and valid measures to
      investigate the relationship between coping style and psychological distress.
      Study quality was assessed according to pre-set criteria. RESULTS: Twelve studies
      (8 cross-sectional and 4 longitudinal designs) involving 1281 patients were
      reviewed. There was considerable heterogeneity in study samples and coping
      measures. Moderate-to-large associations between disengagement coping mechanisms
      (eg, avoidance) and psychological distress were observed. Engagement coping
      strategies (eg, direct action) were not consistently associated with
      psychological distress. CONCLUSIONS: Several studies observed a significant
      relationship between coping styles aimed at disengaging and distancing from
      cancer and increased psychological distress in people with HNC. To understand
      directionality of these associations and develop understanding of temporal
      features of the relationship between coping styles and distress, longitudinal
      designs could be used. This would enable evidence-based recommendations regarding
      psychological interventions (eg, encouraging helpful coping strategies) for
      individuals along their HNC care pathway.

PMID- 28748625
TI  - Multiple Risk Factor Counseling to Promote Heart-healthy Lifestyles in the Chest
      Pain Observation Unit: Pilot Randomized Controlled Trial.
AB  - OBJECTIVE: Admission to the chest pain observation unit (CPOU) may be an
      advantageous time for patients to consider heart-healthy lifestyle changes while
      undergoing diagnostic evaluation to rule out myocardial ischemia. The aim of this
      pragmatic trial was to assess the effectiveness of a multiple risk factor
      intervention in changing CPOU patients' health beliefs and readiness to change
      health behaviors. A secondary aim was to obtain preliminary estimates of the
      intervention's effect on diet, physical activity, and smoking. METHODS: We
      conducted a pilot randomized controlled trial of a moderate-intensity counseling
      intervention that aimed to build motivation to change and problem-solving skills
      in 140 adult patients with at least one modifiable cardiovascular risk factor
      (CRF) who were admitted to the CPOU of an academic emergency department (ED) with
      symptoms of possible acute coronary syndrome. Study patients were randomly
      assigned to full counseling (face-to-face cardiovascular risk assessment and
      personalized counseling on nutrition, physical activity, and smoking cessation in
      the ED, plus two telephone follow-up sessions) or minimal counseling (brief
      instruction [<5 minutes] on benefits of modifying cardiovascular risk factors) by
      a cardiac rehabilitation specialist. We measured Health Belief Model constructs
      for ischemic heart disease, stage of change, and self-reported CRF-related
      behaviors (diet, exercise, and smoking) during 6-month follow-up using previously
      validated measures. We used linear mixed models and logistic regression (with
      generalized estimating equations) to compare continuous and dichotomous
      behavioral outcomes across treatment arms, respectively. RESULTS: Approximately
      20% more patients in the full counseling arm reported having received counseling
      on diet and physical activity during CPOU admission, compared to the minimal
      counseling arm; a similar proportion of patients in both counseling arms reported
      having received advice or assistance in quitting smoking. There were no
      significant differences between treatment arms for any cardiovascular health
      beliefs, readiness to change, or CRF-related behaviors during longitudinal follow
      up. In secondary analyses in both treatment arms combined, however, patients
      showed significant differences between follow-up and baseline measurements:
      increases in the perceived benefits of improving CRF-related behaviors (27.7 vs.
      26.6 on a scale from 7 to 35, p = 0.0001) and increased readiness to change
      dietary behavior and physical activity during follow-up-intake of saturated fat
      (83% vs. 49%), readiness to change fruit and vegetable consumption (83% vs 56%),
      and readiness to perform regular exercise (34% vs. 14%) at 6 months and baseline,
      respectively (p < 0.0001 for all comparisons in both treatment arms combined).
      CONCLUSIONS: A multiple risk factor intervention that focused on increasing
      motivation to change and problem-solving skills did not significantly improve
      behavioral outcomes, compared to minimal counseling. Patients admitted to the
      CPOU demonstrated sustained changes in several cardiovascular health beliefs and
      risk-related behaviors during follow-up; this provides further evidence that the
      CPOU visit is a "teachable moment" for cardiovascular risk reduction. Future
      studies should evaluate the effectiveness of ED-initiated counseling
      interventions to engage patients in changing cardiovascular risk behaviors, in
      coordination with primary care.

PMID- 28748626
TI  - Combining "Bottom-up" and "Top-down" Approaches to Assess the Impact of Food and
      Gastric pH on Pictilisib (GDC-0941) Pharmacokinetics.
AB  - Pictilisib, a weakly basic compound, is an orally administered, potent, and
      selective pan-inhibitor of phosphatidylinositol 3-kinases for oncology
      indications. To investigate the significance of high-fat food and gastric pH on
      pictilisib pharmacokinetics (PK) and enable label recommendations, a dedicated
      clinical study was conducted in healthy volunteers, whereby both top-down
      (population PK, PopPK) and bottom-up (physiologically based PK, PBPK) approaches
      were applied to enhance confidence of recommendation and facilitate the clinical
      development through scenario simulations. The PopPK model identified food (for
      absorption rate constant (Ka )) and proton pump inhibitors (PPI, for relative
      bioavailability (Frel ) and Ka ) as significant covariates. Food and PPI also
      impacted the variability of Frel . The PBPK model accounted for the
      supersaturation tendency of pictilisib, and gastric emptying physiology
      successfully predicted the food and PPI effect on pictilisib absorption. Our
      research highlights the importance of applying both quantitative approaches to
      address critical drug development questions.

PMID- 28748627
TI  - Genetic ablation of carbonic anhydrase IX disrupts gastric barrier function via
      claudin-18 downregulation and acid backflux.
AB  - AIM: This study aimed to explore the molecular mechanisms for the parietal cell
      loss and fundic hyperplasia observed in gastric mucosa of mice lacking the
      carbonic anhydrase 9 (CAIX). METHODS: We assessed the ability of CAIX-knockout
      and WT gastric surface epithelial cells to withstand a luminal acid load by
      measuring the pHi of exteriorized gastric mucosa in vivo using two-photon
      confocal laser scanning microscopy. Cytokines and claudin-18A2 expression was
      analysed by RT-PCR. RESULTS: CAIX-knockout gastric surface epithelial cells
      showed significantly faster pHi decline after luminal acid load compared to WT.
      Increased gastric mucosal IL-1beta and iNOS, but decreased claudin-18A2
      expression (which confer acid resistance) was observed shortly after weaning,
      prior to the loss of parietal and chief cells. At birth, neither inflammatory
      cytokines nor claudin-18 expression were altered between CAIX and WT gastric
      mucosa. The gradual loss of acid secretory capacity was paralleled by an increase
      in serum gastrin, IL-11 and foveolar hyperplasia. Mild chronic proton pump
      inhibition from the time of weaning did not prevent the claudin-18 decrease nor
      the increase in inflammatory markers at 1 month of age, except for IL-1beta.
      However, the treatment reduced the parietal cell loss in CAIX-KO mice in the
      subsequent months. CONCLUSIONS: We propose that CAIX converts protons that either
      backflux or are extruded from the cells rapidly to CO2 and H2 O, contributing to
      tight junction protection and gastric epithelial pHi regulation. Lack of CAIX
      results in persistent acid backflux via claudin-18 downregulation, causing loss
      of parietal cells, hypergastrinaemia and foveolar hyperplasia.

PMID- 28748628
TI  - Reproductive phenology of Creole horses in Ecuador in the absence of photoperiod
      variation: The effects of forage availability and flooding affecting body
      condition of mares.
AB  - Horse reproduction tends to be seasonal. The main adjusting factor in their
      original temperate ranges is photoperiod variation, although it is absent in
      equatorial areas where horses were introduced by European colonizers. Hence,
      dates of reproduction in these areas may be influenced by factors affecting
      mares' conditions and the success of foaling. Here we study reproductive timing
      in Creole horses in Ecuador reared in an extensive production system. We found
      that foaling peaked in August. Mares' conditions showed one peak in June-July,
      before the start of the breeding season, and another in December, and it was
      highly variable along the year. Mares' conditions increased after a period of
      vegetation growth and thus appeared negatively associated with the increment of
      grass greenness (normalized difference vegetation index data). Seasonal flooding
      of some pasturelands during March and April appeared to seriously impair mares'
      conditions and probably influenced the timing of foaling toward the dry season.
      Our results evidenced that horse breeding in these equatorial areas tended to be
      seasonal and point to some key factors that influence phenology by affecting body
      condition of mares, which may have implications for horse biology and management.

PMID- 28748629
TI  - Rethinking reconsent when minors reach adult age in minimal risk studies.

PMID- 28748630
TI  - Transverse myelitis as an unexpected complication following treatment with
      dinutuximab in pediatric patients with high-risk neuroblastoma: A case series.
AB  - Immunotherapy with the anti-GD2 monoclonal antibody ch14.18, or dinutuximab,
      represents an important therapeutic advance in the treatment of pediatric high
      risk neuroblastoma and is now considered part of standard of care in this patient
      population. To date, transverse myelitis as a result of dinutuximab therapy has
      not been reported in clinical trials or in the published literature. We describe
      three patients with clinical symptoms of transverse myelitis, confirmed via
      magnetic resonance imaging, shortly following initiation of dinutuximab. All
      patients were discontinued from dinutuximab treatment and received urgent
      treatment, with rapid improvement in symptoms and resultant functional recovery.

PMID- 28748631
TI  - Reverse Translation for Assessment of Confidence in Animal Models of Multiple
      Sclerosis for Drug Discovery.
AB  - The poor predictive quality of currently used animal models in preclinical
      research is an important cause of the high attrition of promising drug candidates
      for human autoimmune disease in clinical trials. Examples from own work in a
      primate multiple sclerosis (MS) model illustrate that important lessons can be
      learned from a critical reassessment of failed drugs in the animal model, which
      can help improve the animal model and better understand the targeted disease.

PMID- 28748632
TI  - First molecular identification of the vertebrate hosts of Culicoides imicola in
      Europe and a review of its blood-feeding patterns worldwide: implications for the
      transmission of bluetongue disease and African horse sickness.
AB  - Culicoides (Diptera: Ceratopogonidae) are vectors of pathogens that affect
      wildlife, livestock and, occasionally, humans. Culicoides imicola (Kieffer, 1913)
      is considered to be the main vector of the pathogens that cause bluetongue
      disease (BT) and African horse sickness (AHS) in southern Europe. The study of
      blood-feeding patterns in Culicoides is an essential step towards understanding
      the epidemiology of these pathogens. Molecular tools that increase the accuracy
      and sensitivity of traditional methods have been developed to identify the hosts
      of potential insect vectors. However, to the present group's knowledge, molecular
      studies that identify the hosts of C. imicola in Europe are lacking. The present
      study genetically characterizes the barcoding region of C. imicola trapped on
      farms in southern Spain and identifies its vertebrate hosts in the area. The
      report also reviews available information on the blood-feeding patterns of C.
      imicola worldwide. Culicoides imicola from Spain feed on blood of six mammals
      that include species known to be hosts of the BT and AHS viruses. This study
      provides evidence of the importance of livestock as sources of bloodmeals for C.
      imicola and the relevance of this species in the transmission of BT and AHS
      viruses in Europe.

PMID- 28748633
TI  - Depression and anxiety in multiple system atrophy.
AB  - BACKGROUND: It has been noticed that the patients with multiple system atrophy
      (MSA) can accompany with depression and anxiety. This study aimed to establish
      the incidence and determinants of depression and anxiety symptoms in Chinese MSA
      patients. METHODS: A total of 237 MSA patients were enrolled in the study.
      Neuropsychological assessment was performed using Hamilton Depression Rating
      Scale-24 items and Hamilton Anxiety Rating Scale. RESULTS: We found that 62.0%
      and 71.7% patients had at least mild depression and anxiety symptoms,
      respectively. The severity of depression of MSA patients was associated with
      lower educational years (P=.024), longer disease duration (P<.001), and disease
      severity (P<.001). The severity of anxiety was associated with increased disease
      duration (P<.001), disease severity (P=.013), and orthostatic hypotension
      (P=.005). Binary logistic regression showed the determinants of depression and
      anxiety were female gender, longer disease duration, and disease severity.
      CONCLUSION: Depression and anxiety symptoms are common in patients with MSA.
      Neurologists should pay attention to depression and anxiety in patients with MSA,
      especially in female patients and those with longer disease duration and severe
      disease condition.

PMID- 28748634
TI  - Timing of births and oral contraceptive use influences ovarian cancer risk.
AB  - Increasing parity and duration of combined oral contraceptive (COC) use provide
      substantial protection against ovarian carcinoma (cancer). There are limited data
      on the impact of the age of the births or age of COC use on reducing ovarian
      cancer risk. Here, we examined the effects of age at first and last births and
      age at use of COCs using data from studies conducted in Los Angeles County,
      California, USA (1,632 cases, 2,340 controls). After adjusting for the number of
      births, every 5 years that a first birth was delayed reduced the risk of ovarian
      cancer by 13% (95% CI 5-21%; p = 0.003); a first birth after age 35 was
      associated with a 47% lower risk than a first birth before age 25. COC use before
      age 35 was associated with greater protection per year of use than COC use at
      older ages. Considering previously published results as well as the results
      presented here, increasing parity and a later age at births are both important
      protective factors against ovarian cancer and the protection extends over 30 or
      more years from last birth. Current models of the etiology of ovarian cancer do
      not encompass an effect of late age at births. Our result of an attenuation of
      the protective effect with COC use after around age 35 needs further
      investigation as it has not been seen in all studies.

PMID- 28748636
TI  - Compact Cell Settlers for Perfusion Cultures of Microbial (and Mammalian) Cells.
AB  - As microbial secretory expression systems have become well developed for
      microbial yeast cells, such as Saccharomyces cerevisiae and Pichia pastoris, it
      is advantageous to develop high cell density continuous perfusion cultures of
      microbial yeast cells to retain the live and productive yeast cells inside the
      perfusion bioreactor while removing the dead cells and cell debris along with the
      secreted product protein in the harvest stream. While the previously demonstrated
      inclined or lamellar settlers can be used for such perfusion bioreactors for
      microbial cells, the size and footprint requirements of such inefficiently scaled
      up devices can be quite large in comparison to the bioreactor size. Faced with
      this constraint, we have now developed novel, patent-pending compact cell
      settlers that can be used more efficiently with microbial perfusion bioreactors
      to achieve high cell densities and bioreactor productivities. Reproducible
      results from numerous month-long perfusion culture experiments using these
      devices attached to the 5 L perfusion bioreactor demonstrate very high cell
      densities due to substantial sedimentation of the larger live yeast cells which
      are returned to the bioreactor, while the harvest stream from the top of these
      cell settlers is a significantly clarified liquid, containing less than 30% and
      more typically less than 10% of the bioreactor cell concentration. Size of cells
      in the harvest is smaller than that of the cells in the bioreactor. Accumulated
      protein collected from the harvest and rate of protein accumulation is
      significantly (> 6x) higher than the protein produced in repeated fed-batch
      cultures over the same culture duration. (c) 2017 American Institute of Chemical
      Engineers Biotechnol. Prog., 33:913-922, 2017.

PMID- 28748635
TI  - Copy Number Changes Identified Using Whole Exome Sequencing in Nonsyndromic Cleft
      Lip and Palate in a Honduran Population.
AB  - BACKGROUND: The majority of cleft lip with or without cleft palate cases appear
      as an isolated, nonsyndromic entity (NSCLP). With the advent of next generation
      sequencing, whole exome sequencing (WES) has been used to identify single
      nucleotide variants and insertion/deletions which cause or increase the risk of
      NSCLP. However, to our knowledge, there are no published studies using WES in
      NSCLP to investigate copy number changes (CNCs), which are a major component of
      human genetic variation. Our study aimed to identify CNCs associated with NSCLP
      in a Honduran population using WES. METHODS: WES was performed on two to four
      members of 27 multiplex Honduran families. CNCs were identified using two
      algorithms, CoNIFER and XHMM. Priority was given to CNCs that were identified in
      more than one patient and had variant frequencies of less than 5% in reference
      data sets. RESULTS: WES completion was defined as >90% of the WES target at >8 *
      coverage and >80% of the WES target at >20 * coverage. Twenty-four CNCs that met
      our inclusion criteria were identified by both CoNIFER and XHMM. These CNCs were
      confirmed using quantitative PCR. Pedigree analysis produced three CNCs
      corresponding to ADH7, AHR, and CRYZ segregating with NSCLP. Two of the three
      CNCs implicate genes, AHR and ADH7, whose known biological functions could
      plausibly play a role in NSCLP. CONCLUSION: WES can be used to detect candidate
      CNCs that may be involved in the pathophysiology of NSCLP. Birth Defects Research
      109:1257-1267, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28748637
TI  - A new paradigm or a misrepresentation of current communication research and
      teaching?

PMID- 28748638
TI  - A MYB-type transcription factor, MYB2, represses light-harvesting protein genes
      in Cyanidioschyzon merolae.
AB  - While searching for transcriptional regulators that respond to changes in light
      regimes, we identified a MYB domain-containing protein, MYB2, that accumulates
      under dark and other conditions in the unicellular red alga Cyanidioschyzon
      merolae. The isolation and analysis of a MYB2 mutant revealed that MYB2 represses
      the expression of the nuclear-encoded chloroplast RNA polymerase sigma factor
      gene SIG2, which results in the repression of the chloroplast-encoded
      phycobilisome genes that are under its control. Since nuclear-encoded
      phycobilisome and other light-harvesting protein genes are also repressed by
      MYB2, we conclude that MYB2 has a role in repressing the expression of light
      harvesting genes. The MYB2 mutant is sensitive to a prolonged dark incubation,
      indicating the importance of MYB2 for cell viability in the dark.

PMID- 28748639
TI  - How nurses cope with patient death: A systematic review and qualitative meta
      synthesis.
AB  - AIMS AND OBJECTIVES: To review literature on nurses' coping strategies with
      patient death. BACKGROUND: Dealing with the loss of a patient was viewed as one
      of the most demanding and challenging encounters in clinical practice. Those
      nurses who are not competent in coping with patient death may be inadequate in
      supporting dying patients and their family members, and minimise the quality of
      end-of-life care. To get a broader understanding of how nurses cope with patient
      death and to develop meaningful and effective interventions, a systematic review
      which would help underpin the multidimensional approaches is needed. DESIGN: A
      systematic review. METHODS: Exhaustive searching in ten databases: CINAHL Plus,
      EMBASE, MEDLINE, AMED, PsycINFO, ProQuest Health & Medical Complete, ProQuest
      Dissertations & Theses Global, Google Scholar, EThOS and CareSearch. Meta
      aggregation was used to synthesise the findings of the included studies. RESULTS:
      This systematic review aggregated ten categories from the sixteen qualitative
      studies included, and then two synthesised findings were derived: intrinsic
      resources and extrinsic resources. The intrinsic resources consisted of setting
      boundaries, reflection, crying, death beliefs, life and work experience, and
      daily routines and activity. The extrinsic resources were comprised of talking
      and being heard, spiritual practices, education and programmes, and debriefing.
      CONCLUSION: This systematic review synthesised the findings about what resources
      nurses use when coping with patient death and made recommendations on future
      directions. Areas which could be developed to improve deficiencies that nurses
      had when faced with the losses of their patients were identified. Nurses need
      more support resources, which better assist them in coping with patient death.
      RELEVANCE TO CLINICAL PRACTICE: The results of this systematic review could
      provide evidence for nurses' coping strategies when dealing with patient death,
      and the recommendations could be employed by nurses to cope with the losses of
      patients.

PMID- 28748640
TI  - Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the
      endometrium of women with endometrial cancer and women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: Women with a prior history of polycystic ovary syndrome (PCOS) have an
      increased risk of endometrial cancer (EC). AIM: To investigate whether the
      endometrium of women with PCOS possesses gene expression changes similar to those
      found in EC. DESIGN AND METHODS: Patients with EC, PCOS and control women
      unaffected by either PCOS or EC were recruited into a cross-sectional study at
      the Nottingham University Hospital, UK. For RNA sequencing, representative
      individual endometrial biopsies were obtained from women with EC, PCOS and a
      woman unaffected by PCOS or EC. Expression of a subset of differentially
      expressed genes identified by RNA sequencing, including NAD(P)H quinone
      dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR
      validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus
      endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1
      was validated by immunohistochemistry in EC samples from a separate cohort (n =
      91) comprised of consecutive patients who underwent hysterectomy at St Mary's
      Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women
      with histologically normal endometrium who underwent hysterectomy for genital
      prolapse were also included. Informed consent and local ethics approval were
      obtained for the study. RESULTS: We show for the first that NQO1 expression is
      significantly increased in the endometrium of women with PCOS and EC.
      Immunohistochemistry confirms significantly increased NQO1 protein expression in
      EC relative to nonmalignant endometrial tissue (P < .0001). CONCLUSIONS: The
      results obtained here support a previously unrecognized molecular link between
      PCOS and EC involving NQO1.

PMID- 28748641
TI  - EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.
AB  - Hymenoptera venom allergy is a potentially life-threatening allergic reaction
      following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions
      have been reported in up to 7.5% of adults and up to 3.4% of children. They can
      be mild and restricted to the skin or moderate to severe with a risk of life
      threatening anaphylaxis. Patients should carry an emergency kit containing an
      adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the
      severity of their previous sting reaction(s). The only treatment to prevent
      further systemic sting reactions is venom immunotherapy. This guideline has been
      prepared by the European Academy of Allergy and Clinical Immunology's (EAACI)
      Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen
      Immunotherapy initiative. The guideline aims to provide evidence-based
      recommendations for the use of venom immunotherapy, has been informed by a formal
      systematic review and meta-analysis and produced using the Appraisal of
      Guidelines for Research and Evaluation (AGREE II) approach. The process included
      representation from a range of stakeholders. Venom immunotherapy is indicated in
      venom-allergic children and adults to prevent further moderate-to-severe systemic
      sting reactions. Venom immunotherapy is also recommended in adults with only
      generalized skin reactions as it results in significant improvements in quality
      of life compared to carrying an adrenaline autoinjector. This guideline aims to
      give practical advice on performing venom immunotherapy. Key sections cover
      general considerations before initiating venom immunotherapy, evidence-based
      clinical recommendations, risk factors for adverse events and for relapse of
      systemic sting reaction, and a summary of gaps in the evidence.

PMID- 28748643
TI  - Protein supplements and adolescent athletes: A pilot study investigating the risk
      knowledge, motivations and prevalence of use.
AB  - AIM: Protein-based sports supplements are among the more common types of
      nutrition supplements consumed by athletes; however, there is currently limited
      data investigating the knowledge, motivations and occurrence of use among the
      adolescent population (13-18 years). This pilot study looks to obtain initial
      data regarding the use of protein supplements in this population. METHODS: This
      study investigates the understanding and occurrence of protein supplement use in
      87 adolescent athletes based in an Australian capital city who compete in a
      variety of sports. Sources of information, regularity of use, purchasing habits,
      associated risk knowledge and supplement beliefs were examined using a self
      reported, written questionnaire. RESULTS: A total of 60% (n = 52) of athletes
      reported using protein supplements, with a positive relationship between age and
      use (P < 0.05); 48 participants (55%) perceived risks associated with protein
      supplement consumption, with the most common risk reported as 'I don't know'
      (22%). Coaches were found to initiate protein supplement use more than other
      figures in the athlete's life (50%) and were the primary source of information
      regarding supplements (58%). It was found that 19% of adolescent athletes
      obtained information about protein supplements from the Internet, and 17% of all
      consumers purchase their supplements online. CONCLUSIONS: The evident lack of
      knowledge regarding protein supplements demonstrates a necessity for further
      education of athletes, coaches and families regarding the responsible purchasing
      and use of protein supplements in the current landscape of sports nutrition.
      Future research should further explore the role of the Internet in protein
      supplement purchase and education.

PMID- 28748642
TI  - Noonan syndrome in diverse populations.
AB  - Noonan syndrome (NS) is a common genetic syndrome associated with gain of
      function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been
      well characterized in populations of European descent with less attention given
      to other groups. In this study, individuals from diverse populations with NS were
      evaluated clinically and by facial analysis technology. Clinical data and images
      from 125 individuals with NS were obtained from 20 countries with an average age
      of 8 years and female composition of 46%. Individuals were grouped into
      categories of African descent (African), Asian, Latin American, and
      additional/other. Across these different population groups, NS was phenotypically
      similar with only 2 of 21 clinical elements showing a statistically significant
      difference. The most common clinical characteristics found in all population
      groups included widely spaced eyes and low-set ears in 80% or greater of
      participants, short stature in more than 70%, and pulmonary stenosis in roughly
      half of study individuals. Using facial analysis technology, we compared 161
      Caucasian, African, Asian, and Latin American individuals with NS with 161 gender
      and age matched controls and found that sensitivity was equal to or greater than
      94% for all groups, and specificity was equal to or greater than 90%. In summary,
      we present consistent clinical findings from global populations with NS and
      additionally demonstrate how facial analysis technology can support clinicians in
      making accurate NS diagnoses. This work will assist in earlier detection and in
      increasing recognition of NS throughout the world.

PMID- 28748644
TI  - Diversity and stability of coral endolithic microbial communities at a naturally
      high pCO2 reef.
AB  - The health and functioning of reef-building corals is dependent on a balanced
      association with prokaryotic and eukaryotic microbes. The coral skeleton harbours
      numerous endolithic microbes, but their diversity, ecological roles and responses
      to environmental stress, including ocean acidification (OA), are not well
      characterized. This study tests whether pH affects the diversity and structure of
      prokaryotic and eukaryotic algal communities associated with skeletons of Porites
      spp. using targeted amplicon (16S rRNA gene, UPA and tufA) sequencing. We found
      that the composition of endolithic communities in the massive coral Porites spp.
      inhabiting a naturally high pCO2 reef (avg. pCO2 811 MUatm) is not significantly
      different from corals inhabiting reference sites (avg. pCO2 357 MUatm),
      suggesting that these microbiomes are less disturbed by OA than previously
      thought. Possible explanations may be that the endolithic microhabitat is highly
      homeostatic or that the endolithic micro-organisms are well adapted to a wide pH
      range. Some of the microbial taxa identified include nitrogen-fixing bacteria
      (Rhizobiales and cyanobacteria), algicidal bacteria in the phylum Bacteroidetes,
      symbiotic bacteria in the family Endozoicomoniaceae, and endolithic green algae,
      considered the major microbial agent of reef bioerosion. Additionally, we test
      whether host species has an effect on the endolithic community structure. We show
      that the endolithic community of massive Porites spp. is substantially different
      and more diverse than that found in skeletons of the branching species
      Seriatopora hystrix and Pocillopora damicornis. This study reveals highly diverse
      and structured microbial communities in Porites spp. skeletons that are possibly
      resilient to OA.

PMID- 28748647
TI  - Contents - Eur. J. Immunol. 3/2004.

PMID- 28748646
TI  - Small airway dysfunction in chronic hypersensitivity pneumonitis.
AB  - BACKGROUND AND OBJECTIVE: Lung biopsies from patients with hypersensitivity
      pneumonitis (HP) have demonstrated small airway (SA) involvement, but there is no
      information concerning SA function in HP, and it is unknown whether
      pharmacological treatment could modify its function. SA function in patients with
      chronic HP using ultrasonic pneumography (UPG) and impulse oscillometry (IOS) was
      explored. We also compared initial results with those obtained after 4 weeks of
      standardized treatment with azathioprine and prednisone. METHODS: The study group
      consisted of adults with recent diagnoses of HP. All patients completed UPG, IOS,
      spirometry, body plethysmography, single-breath carbon monoxide diffusing
      capacity (DLCO ) and the 6-min walk test (6MWT). The fraction of exhaled nitric
      oxide (FENO ) was obtained to assess eosinophilic airway inflammation.
      Measurements were taken at diagnosis and after 4 weeks of treatment. RESULTS: A
      total of 20 consecutive patients (16 women) with chronic HP participated in the
      study. Median age was 50 years (interquartile range (IQR): 42-54). At diagnosis,
      the UPG phase 3 slope was abnormally high, consistent with maldistribution of
      ventilation. For IOS, all patients had low reactance at 5 Hz (X5) and elevated
      reactance area (AX) reflecting low compliance, and only eight (40%) patients had
      elevated R5 (resistance at 5 Hz (total)) and R5-20 (resistance at 5 Hz-resistance
      at 20 Hz (peripheral)) attributed to SA resistance. In contrast, FENO parameters
      were within normal limits. After treatment, forced vital capacity (FVC), the 6
      min walk distance and the distribution of ventilation showed significant
      improvement, although DLCO did not. CONCLUSION: Patients with chronic HP have SA
      abnormalities that are partially revealed by the UPG and IOS tests. Lung volumes,
      but not gas exchange, improved after treatment with azathioprine and prednisone.

PMID- 28748648
TI  - Accurate template-based modeling in CASP12 using the IntFOLD4-TS, ModFOLD6, and
      ReFOLD methods.
AB  - Our aim in CASP12 was to improve our Template-Based Modeling (TBM) methods
      through better model selection, accuracy self-estimate (ASE) scores and
      refinement. To meet this aim, we developed two new automated methods, which we
      used to score, rank, and improve upon the provided server models. Firstly, the
      ModFOLD6_rank method, for improved global Quality Assessment (QA), model ranking
      and the detection of local errors. Secondly, the ReFOLD method for fixing errors
      through iterative QA guided refinement. For our automated predictions we
      developed the IntFOLD4-TS protocol, which integrates the ModFOLD6_rank method for
      scoring the multiple-template models that were generated using a number of
      alternative sequence-structure alignments. Overall, our selection of top models
      and ASE scores using ModFOLD6_rank was an improvement on our previous approaches.
      In addition, it was worthwhile attempting to repair the detected errors in the
      top selected models using ReFOLD, which gave us an overall gain in performance.
      According to the assessors' formula, the IntFOLD4 server ranked 3rd/5th (average
      Z-score > 0.0/-2.0) on the server only targets, and our manual predictions
      (McGuffin group) ranked 1st/2nd (average Z-score > -2.0/0.0) compared to all
      other groups.

PMID- 28748649
TI  - Vortex-assisted liquid-liquid microextraction of strontium from water samples
      using 4',4"(5")-di-(tert-butylcyclohexano)-18-crown-6 and tetraphenylborate.
AB  - A vortex-assisted liquid-liquid microextraction method was developed for the
      chromatographic determination of strontium in aqueous samples. In the method,
      strontium was complexed with 4',4"(5")-di-(tert-butylcyclohexano)-18-crown-6 in
      the presence of tetraphenylborate as the counter anion, which increased the
      hydrophobicity of the ion-association complex, resulting in its improved
      extraction into 1-octanol. Strontium from the organic phase was stripped with
      nitric acid back to aqueous solution and determined by ion chromatography. The
      optimum microextraction conditions were as follows: 2.0 mL aqueous samples with 3
      mM tetraphenylborate; 150 MUL of 1-octanol as the extractant phase with 10 mM
      DtBuCH18C6; vortex extraction time for 10 s; centrifugation at 6000 rpm for 4
      min; stripping by 0.1 M nitric acid. Under the optimum conditions, the detection
      limit for strontium was 0.005 mg/L. The calibration curves showed good linearity
      over the range between 0.01 and 2.5 mg/L. Intra- and interday precisions of the
      present method were satisfactory with relative standard deviations of 1.7 and
      2.1%, respectively.

PMID- 28748650
TI  - Autopsy findings in EPG5-related Vici syndrome with antenatal onset.
AB  - Vici syndrome is one of the most extensive inherited human multisystem disorders
      and due to recessive mutations in EPG5 encoding a key autophagy regulator with a
      crucial role in autophagosome-lysosome fusion. The condition presents usually
      early in life, with features of severe global developmental delay, profound
      failure to thrive, (acquired) microcephaly, callosal agenesis, cataracts,
      cardiomyopathy, hypopigmentation, and combined immunodeficiency. Clinical course
      is variable but usually progressive and associated with high mortality. Here, we
      present a fetus, offspring of consanguineous parents, in whom callosal agenesis
      and other developmental brain abnormalities were detected on fetal ultrasound
      scan (US) and subsequent MRI scan in the second trimester. Postmortem examination
      performed after medically indicated termination of pregnancy confirmed CNS
      abnormalities and provided additional evidence for skin hypopigmentation, nascent
      cataracts, and hypertrophic cardiomyopathy. Genetic testing prompted by a
      suggestive combination of features revealed a homozygous EPG5 mutation (c.5870
      1G>A) predicted to cause aberrant splicing of the EPG5 transcript. Our findings
      expand the phenotypical spectrum of EPG5-related Vici syndrome and suggest that
      this severe condition may already present in utero. While callosal agenesis is
      not an uncommon finding in fetal medicine, additional presence of
      hypopigmentation, cataracts and cardiomyopathy is rare and should prompt EPG5
      testing.

PMID- 28748651
TI  - Emergent programme theories of a national quality register - a longitudinal study
      in Swedish elderly care.
AB  - RATIONALE, AIM, AND OBJECTIVE: This study aimed to explore programme theories of
      a national quality register. A programme theory is a bundle of assumptions
      underpinning how and why an improvement initiative functions. The purpose was to
      examine and establish programme theories of a national quality register widely
      used in Sweden: Senior alert. The paper reports on how programme theories among
      change recipients emerge in relation to the established programme theory of the
      initiator. METHODS: A qualitative approach and a longitudinal research design
      were used. To develop programme theories among change recipients, individual
      semistructured interviews were conducted. Three sets of interviews were conducted
      in the period of 2011 to 2013, totalling 22 interviews. In addition, 4
      participant observations were made. To develop the initiator's programme theory,
      an iterative multistage collaboration process between the researchers and the
      initiator was used. A directed content analysis was used to analyse data.
      FINDINGS: The initiator and change recipients described similar programme logics,
      but differing programme theories. With time, change recipients' programme
      theories emerged. Their programme theories converged and became more like the
      programme theory of the initiator. CONCLUSIONS: This study has demonstrated the
      importance of making both the initiator's and change recipients' programme
      theories explicit. To learn about conditions for improvement initiatives,
      comparisons between their programme theories are valuable. Differences in
      programme theories provide information on how initiators can customize support
      for their improvement initiatives. Similar programme logics can be underpinned by
      different programme theories, which can be deceptive. Programme theories emerge
      over time and need to be understood as dynamic phenomena.

PMID- 28748652
TI  - Bleeding-related hospital admissions and 30-day readmissions in patients with non
      valvular atrial fibrillation treated with dabigatran versus warfarin.
AB  - : Essentials Bleeding is a common cause of hospital admission and readmission in
      oral anticoagulant users. Patients with dabigatran and warfarin were included to
      assess hospital admission risk. Dabigatran users had a higher risk of 30-day
      readmission with bleeding than warfarin users. Close monitoring following
      hospital discharge for dabigatran-related bleeding is warranted. SUMMARY:
      Background Reducing 30-day hospital readmission is a policy priority worldwide.
      Warfarin-related bleeding is among the most common cause of hospital admissions
      as a result of adverse drug events. Compared with warfarin, dabigatran achieves a
      full anticoagulation effect more quickly following its initiation; hence it may
      lead to early-onset bleeds. Objectives To compare the incidence of bleeding
      related hospital admissions and 30-day readmissions with dabigatran vs. warfarin
      in patients with non-valvular atrial fibrillation (NVAF). Methods This was a
      retrospective cohort study using a population-wide database managed by the Hong
      Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through to
      2014 and prescribed dabigatran or warfarin were 1:1 matched by propensity score.
      The incidence rate of hospital admission with bleeding (a composite of
      gastrointestinal bleeding, intracranial hemorrhage and bleeding at other sites)
      was assessed. Results Among the 51 946 patients with NVAF, 8309 users of
      dabigatran or warfarin were identified, with 5160 patients matched by propensity
      score. The incidence of first hospitalized bleeding did not differ significantly
      between groups (incidence rate ratio, 0.92; 95% confidence interval [CI], 0.66
      1.28). Among patients who were continuously prescribed their initial
      anticoagulants upon discharge, dabigatran use was associated with a higher risk
      of 30-day readmission with bleeding over warfarin (adjusted hazard ratio, 2.87;
      95%CI, 1.10-7.43). Conclusion When compared with warfarin, dabigatran was
      associated with a comparable incidence of first hospital admission but a higher
      risk of 30-day redmission with respect to bleeding. Close early monitoring of
      patients initiated on dabigatran following hospital discharge for bleeding is
      warranted.

PMID- 28748653
TI  - Oral bexarotene for post-transplant cutaneous T-cell lymphoma.
AB  - Organ transplant recipients receiving immunosuppression have an increased risk of
      developing post-transplant lymphoproliferative diseases (PTLDs). Traditionally,
      PTLDs refer to Epstein-Barr virus (EBV)-induced B-cell lymphoma. However, post
      transplant T-cell lymphoma may also occur and tends to have a poorer response to
      reduced immunosuppressive therapy. As such, additional therapy is often needed
      for post-transplant T-cell lymphoma, including post-transplant cutaneous T-cell
      lymphoma (PT-CTCL). We present only the third case of PT-CTCL occurring after
      liver transplantation. The patient was diagnosed with stage IB mycosis fungoides
      (MF). His lesions were refractory to multiple skin-directed therapies, and so he
      was given oral bexarotene 150 mg daily and his oral tacrolimus dose was decreased
      to 2 mg daily. Remarkably, his MF patches have demonstrated a complete response
      to oral bexarotene 75 mg daily without recurrence over 11 years of follow-up. He
      developed hypertriglyceridemia with bexarotene 150 mg, so his dose was decreased
      to 75 mg, without loss of response. Our report is the second to describe PT-CTCL
      demonstrating a long-term complete response to oral bexarotene. Given its anti
      carcinogenic properties and favorable toxicity profile, oral bexarotene
      represents an appealing treatment option for PT-CTCL refractory to skin-directed
      therapies.

PMID- 28748654
TI  - Review article: Does acupuncture have a role in providing analgesia in the
      emergency setting? A systematic review and meta-analysis.
AB  - Acupuncture might offer a novel approach to improve ED pain management. Our
      primary aim was to assess the efficacy of acupuncture in the emergency setting
      while secondary objectives were to explore its suitability through its side
      effect profile, patient satisfaction, cost, administration time and points used.
      Seven databases and Google Scholar were searched up to 31 July 2016 using MeSH
      descriptors for three overarching themes concerning acupuncture, pain management
      and emergency medicine. Meta-analysis was performed on randomised trials for
      three comparator groups: acupuncture versus sham, acupuncture versus standard
      analgesia care and acupuncture-as-an-adjunct to standard care, to calculate the
      standardised mean difference and weighted mean difference for pain scores out of
      10. Data for secondary outcomes was extracted from both randomised and
      observational studies. Nineteen randomised controlled trials and 11 uncontrolled
      observational studies totaling 3169 patients were retrieved after exclusions.
      Meta-analyses were performed on data from 14 randomised controlled trials
      representing 1210 patients. The three resulting comparator groups (as above)
      resulted in standardised mean differences of 1.08, 0.02 and 1.68, and weighted
      mean differences of 1.60, -0.04 and 2.84, respectively (all positive figures
      favour acupuncture). Where measured, acupuncture appears to be associated with
      improved patient satisfaction, lower cost and a low adverse effects profile. The
      data available were inadequate to ascertain the effect of acupuncture on
      analgesia use. Significant study bias was found, especially with respect to
      practitioner and patient blinding. We conclude that for some acute pain
      conditions in the ED, acupuncture was clinically effective compared to sham and
      non-inferior to conventional therapy. As an adjunct, limited data was found
      indicating superiority to standard analgesia care. Further studies will elucidate
      the most appropriate acupuncture training and techniques, use as an adjunct and
      the clinical situations in which they can be best applied.

PMID- 28748655
TI  - High throughput automated microbial bioreactor system used for clone selection
      and rapid scale-down process optimization.
AB  - High throughput automated fermentation systems have become a useful tool in early
      bioprocess development. In this study, we investigated a 24 x 15 mL single use
      microbioreactor system, ambr 15f, designed for microbial culture. We compared the
      fed-batch growth and production capabilities of this system for two Escherichia
      coli strains, BL21 (DE3) and MC4100, and two industrially relevant molecules, hGH
      and scFv. In addition, different carbon sources were tested using bolus, linear
      or exponential feeding strategies, showing the capacity of the ambr 15f system to
      handle automated feeding. We used power per unit volume (P/V) as a scale
      criterion to compare the ambr 15f with 1 L stirred bioreactors which were
      previously scaled-up to 20 L with a different biological system, thus showing a
      potential 1,300 fold scale comparability in terms of both growth and product
      yield. By exposing the cells grown in the ambr 15f system to a level of shear
      expected in an industrial centrifuge, we determined that the cells are as robust
      as those from a bench scale bioreactor. These results provide evidence that the
      ambr 15f system is an efficient high throughput microbial system that can be used
      for strain and molecule selection as well as rapid scale-up. (c) 2017 The Authors
      Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American
      Institute of Chemical Engineers Biotechnol. Prog., 34:58-68, 2018.

PMID- 28748656
TI  - Metal-Free, Initiator-Free Graphene Oxide-Catalyzed Trifluoromethylation of
      Arenes.
AB  - The direct C-H trifluoromethylation of arenes catalyzed by graphene oxide (GO)
      under safe conditions is described. This strategy is metal-free, initiator-free,
      safe, and scalable. It employs a readily available CF3 source and the reaction
      can be easily controlled to obtain a mono-trifluorinated product. This method
      opens a new avenue for GO-catalyzed chemistry.

PMID- 28748657
TI  - One Dimensional Silver-based Nanomaterials: Preparations and Electrochemical
      Applications.
AB  - One dimensional (1D) silver-based nanomaterials have a great potential in various
      fields because of their high specific surface area, high electric conductivity,
      optoelectronic properties, mechanical flexibility and high electro-catalytic
      efficiency. In this Review, the preparations of 1D silver-based nanomaterials is
      classified by structure composed of simple silver nanowires/rods/belts/tubes,
      core-shells, and hybrids. The latest applications based on 1D silver
      nanomaterials and their composite materials are summarized systematically
      including electrochemical capacitors, lithium-ion/lithium-oxygen batteries,
      electrochemical sensors and electrochemical catalysis. The preparation process,
      tailored material properties and electrochemical applications are discussed.

PMID- 28748658
TI  - Engineering Globular Protein Vesicles through Tunable Self-Assembly of
      Recombinant Fusion Proteins.
AB  - Vesicles assembled from folded, globular proteins have potential for functions
      different from traditional lipid or polymeric vesicles. However, they also
      present challenges in understanding the assembly process and controlling vesicle
      properties. From detailed investigation of the assembly behavior of recombinant
      fusion proteins, this work reports a simple strategy to engineer protein vesicles
      containing functional, globular domains. This is achieved through tunable self
      assembly of recombinant globular fusion proteins containing leucine zippers and
      elastin-like polypeptides. The fusion proteins form complexes in solution via
      high affinity binding of the zippers, and transition through dynamic coacervates
      to stable hollow vesicles upon warming. The thermal driving force, which can be
      tuned by protein concentration or temperature, controls both vesicle size and
      whether vesicles are single or bi-layered. These results provide critical
      information to engineer globular protein vesicles via self-assembly with desired
      size and membrane structure.

PMID- 28748660
TI  - Memorial - Andrew A. Lackner, D.V.M., Ph.D. 1960-2017.

PMID- 28748659
TI  - Mauritian cynomolgus macaques with M3M4 MHC genotype control SIVmac251 infection.
AB  - BACKGROUND: Understanding natural HIV control may lead to new preventative or
      therapeutic strategies. Several protective major histocompatibility complex (MHC)
      genotypes were found in humans and rhesus macaques. Here, we report a simian
      immunodeficiency virus (SIV) controller MHC genotype in Mauritian cynomolgus
      macaques (MCMs). METHODS: Twelve MHC-genotyped MCMs were infected with SIVmac251
      and monitored for viral loads and CD4+ T-cell counts. RESULTS: Two macaques with
      M3M4 genotype exhibited the lowest peak viral loads (log plasma SIV RNA
      copies/mL), nearly 3 logs lower than those in most macaques with other MHC
      haplotype combinations, and set point viral loads below the level of detection
      limit by RT-qPCR (<2 log RNA copies/mL). They maintained healthy CD4+ T-cell
      counts of >500 cells/MUL blood, while CD4 counts in the vast majority of other
      macaques were below this level. CONCLUSIONS: The M3M4 MHC genotype may confer
      enhanced control of SIV replication in MCMs.

PMID- 28748661
TI  - Emerging diagnostic challenges and characteristics of simian betaretrovirus
      infections in captive macaque colonies.
AB  - To better understand Simian betaretrovirus (SRV) seropositivity in virus-negative
      macaques, we transfused blood from SRV-infected or suspect donors into
      immunosuppressed naive recipients. Our results do not support typical SRV1-5
      infection as the cause, but provide evidence for several possibilities including
      serological artifact, new/different SRV, or an endogenous virus.

PMID- 28748663
TI  - Introduction.

PMID- 28748662
TI  - Repeated administration of high-dose depot medroxyprogesterone acetate does not
      alter SHIVSF162p3 viral kinetics and tenofovir pharmacokinetics when delivered
      via intravaginal rings.
AB  - BACKGROUND: Intravaginal rings (IVR) for HIV prevention will likely be used by
      women on depot medroxyprogesterone acetate (DMPA) hormonal contraception. We used
      pigtailed macaques to evaluate the effects of DMPA on tenofovir disoproxil
      fumarate (TDF) IVR pharmacokinetics and viral shedding. METHODS: Mucosal
      tenofovir (TFV) levels were compared in SHIVSF162p3 -negative DMPA-treated (n=4)
      and normally cycling (n=6) macaques receiving TDF IVRs. Plasma viremia and
      vaginal shedding were determined in groups of SHIVSF162p3 -positive DMPA-treated
      (n=6) and normally cycling (n=5) macaques. RESULTS: Similar median vaginal fluid
      TFV concentrations were observed in the DMPA-treated and cycling macaques over 4
      weeks (1.2*105 and 1.1.*105  ng/mL, respectively). Median plasma viremia and
      vaginal shedding AUC of the DMPA-treated (2.73*107 and 8.15*104 copies/mL,
      respectively) and cycling macaques (3.98*107 and 1.47*103 copies/mL,
      respectively) were statistically similar. CONCLUSIONS: DMPA does not affect TDF
      IVR pharmacokinetics or SHIV shedding.

PMID- 28748664
TI  - Long-term efficient control of SIV infection in macaques is associated with an
      intact intestinal barrier.
AB  - Hallmarks of SIV infection are early depletion of gut CD4 T cells and diminished
      intestinal integrity. Comprehensive studies on colon biopsies of SIV-infected
      macaques efficiently controlling infection revealed that in contrast to viremic
      and failing controllers, elite controllers show preserved CD4 T cells, and low
      viral load, apoptosis, and inflammation.

PMID- 28748665
TI  - CD4+ Cell infiltration into subcutaneous adipose tissue is not indicative of
      productively infected cells during acute SHIV infection.
AB  - Limited longitudinal data exist on the effect of HIV on adipose tissue (AT). We
      found an increase in CD4+ cells and detectable SHIV-RNA in AT during acute SHIV
      infection. SHIV-RNA+ cells were rare, suggesting that AT is unlikely to be a
      major source of productively infected cells in SHIV infection.

PMID- 28748666
TI  - 34th Annual Symposium on Nonhuman Primate Models for AIDS.

PMID- 28748667
TI  - A model of genital herpes simplex virus Type 1 infection in Rhesus Macaques.
AB  - BACKGROUND: Although HSV-2 is the major cause of genital lesions, HSV-1 accounts
      for half of new cases in developed countries. METHODS: Three healthy SHIV-SF162P3
      infected Indian rhesus macaques were inoculated with 4*108 pfu of HSV-1 twice,
      with the second inoculation performed after the vaginal mucosa was gently abraded
      with a cytobrush. RESULTS: HSV-1 DNA was detected in vaginal swabs 5 days after
      the second but not the first inoculation in all three macaques. An increase in
      inflammatory cytokines was detected in the vaginal fluids of the animals with no
      or intermittent shedding. Higher frequency of blood alpha4 beta7high CD4+ T cells
      was measured in the animals with consistent and intermitted shedding, while a
      decrease in the frequency of CD69+ CD4+ T cells was present in all animals.
      CONCLUSIONS: This macaque model of genital HSV-1 could be useful to study the
      impact of the growing epidemic of genital HSV-1 on HIV infection.

PMID- 28748668
TI  - Identification of novel simian endogenous retroviruses that are indistinguishable
      from simian retrovirus (SRV) on current SRV diagnostic assays.
AB  - Simian betaretroviruses include the well-known exogenous simian retroviruses (SRV
      1 through SRV-8), and some closely related simian endogenous retroviruses (SERV).
      Here, we characterized two new viral genomes, which appear to represent novel
      SERVs but have characteristics of both SRV and SERV highlighting the need to
      develop new assays providing molecular and serologic differentiation of SERV and
      SRV to avoid false positives.

PMID- 28748669
TI  - Is clinical communication the one area of clinical oncology that needs no new
      ideas?

PMID- 28748670
TI  - Whole genome detection of signature of positive selection in African cattle
      reveals selection for thermotolerance.
AB  - As African indigenous cattle evolved in a hot tropical climate, they have
      developed an inherent thermotolerance; survival mechanisms include a light
      colored and shiny coat, increased sweating, and cellular and molecular mechanisms
      to cope with high environmental temperature. Here, we report the positive
      selection signature of genes in African cattle breeds which contribute for their
      heat tolerance mechanisms. We compared the genomes of five indigenous African
      cattle breeds with the genomes of four commercial cattle breeds using cross
      population composite likelihood ratio (XP-CLR) and cross-population extended
      haplotype homozygosity (XP-EHH) statistical methods. We identified 296 (XP-EHH)
      and 327 (XP-CLR) positively selected genes. Gene ontology analysis resulted in 41
      biological process terms and six Kyoto Encyclopedia of Genes and Genomes
      pathways. Several genes and pathways were found to be involved in oxidative
      stress response, osmotic stress response, heat shock response, hair and skin
      properties, sweat gland development and sweating, feed intake and metabolism, and
      reproduction functions. The genes and pathways identified directly or indirectly
      contribute to the superior heat tolerance mechanisms in African cattle
      populations. The result will improve our understanding of the biological
      mechanisms of heat tolerance in African cattle breeds and opens an avenue for
      further study.

PMID- 28748671
TI  - Ti6Al4V laser surface preparation and functionalization using hydroxyapatite for
      biomedical applications.
AB  - This work presents a novel texture design for implants surface functionalization,
      through the creation of line-shaped textures on Ti6Al4V surfaces and subsequent
      sintering of hydroxyapatite (HAp) powder into the designated locations. HAp-rich
      locations were designed to avoid HAp detachment during insertion, thus
      guaranteeing an effective osseointegration. This process starts by creating
      textured lines using a Nd:YAG laser, filling these lines with HAp powder and
      sintering HAp using a CO2 laser. The adhesion of HAp is known to be influenced by
      HAp sintering parameters, especially laser power and scanning speed and also by
      the textured lines manufacturing. Different laser parameters combinations were
      used to assess the sintering and adhesion of HAp to the textured lines. HAp
      adhesion was assessed by performing high energy ultrasonic cavitation tests and
      sliding tests mimicking an implant insertion, with Ti6Al4V/HAp specimens sliding
      against animal bone. The HAp content retained after these tests was measured and
      results showed that an excellent HAp sintering and adhesion was achieved when
      using a scan speed of 1 mm/s and laser power between 9 and 9.6 W. It is important
      to emphasize that results indicated that the HAp bioactivity was maintained when
      using these conditions, validating this functionalization process for the
      production of hip prosthesis with improved bioactivity. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1534-1545,
      2018.

PMID- 28748672
TI  - Is there an Association between Migraine and Gastrointestinal Disorders?
AB  - Migraine is a primary episodic headache disorder that represents a substantial
      burden and disability worldwide. Its pathogenesis is multifactorial and remains
      hitherto poorly elucidated. An interesting but less-well-known association is
      that between migraine and gastrointestinal disorders. We have reviewed the
      literature for relevant papers reporting on the clinical association between
      migraine and gastrointestinal symptoms. Several studies have shown different
      gastrointestinal diseases to be associated with migraine, but the underlining
      pathophysiology remains elusive. The data gathered and analyzed have shown great
      variability across studies, making it impossible to draw definitive conclusions.
      Further research is required to elucidate this potential relationship. An
      understanding of the relationship between migraine and gastrointestinal disorders
      is of great clinical importance for prompt diagnosis and treatment.

PMID- 28748673
TI  - Neurological Complications during Treatment of Middle East Respiratory Syndrome.
AB  - BACKGROUND AND PURPOSE: Middle East respiratory syndrome (MERS) has a high
      mortality rate and pandemic potential. However, the neurological manifestations
      of MERS have rarely been reported since it first emerged in 2012. METHODS: We
      evaluated four patients with laboratory-confirmed MERS coronavirus (CoV)
      infections who showed neurological complications during MERS treatment. These 4
      patients were from a cohort of 23 patients who were treated at a single
      designated hospital during the 2015 outbreak in the Republic of Korea. The
      clinical presentations, laboratory findings, and prognoses are described.
      RESULTS: Four of the 23 admitted MERS patients reported neurological symptoms
      during or after MERS-CoV treatment. The potential diagnoses in these four cases
      included Bickerstaff's encephalitis overlapping with Guillain-Barre syndrome,
      intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies.
      Neurological complications did not appear concomitantly with respiratory
      symptoms, instead being delayed by 2-3 weeks. CONCLUSIONS: Neuromuscular
      complications are not rare during MERS treatment, and they may have previously
      been underdiagnosed. Understanding the neurological manifestations is important
      in an infectious disease such as MERS, because these symptoms are rarely
      evaluated thoroughly during treatment, and they may interfere with the prognosis
      or require treatment modification.

PMID- 28748674
TI  - Prognosis of Patients with Behavioral Variant Frontotemporal Dementia Who have
      Focal Versus Diffuse Frontal Atrophy.
AB  - BACKGROUND AND PURPOSE: Only a few studies have investigated the relationship
      between different subtypes and disease progression or prognosis in patients with
      behavioral variant frontotemporal dementia (bvFTD). Since a localized injury
      often produces more focal signs than a diffuse injury, we hypothesized that the
      clinical characteristics differ between patients with bvFTD who show diffuse
      frontal lobe atrophy (D-type) on axial magnetic resonance imaging (MRI) scans
      versus those with focal or circumscribed frontal lobe atrophy (F-type). METHODS:
      In total, 94 MRI scans (74 scans from bvFTD and 20 scans from age-matched normal
      controls) were classified into 35 D- and 39 F-type bvFTD cases based on an axial
      MRI visual rating scale. We compared baseline clinical characteristics,
      progression in motor and cognitive symptoms, and survival times between D- and F
      types. Survival analyses were performed for 62 of the 74 patients. RESULTS: While
      D-type performed better on neuropsychological tests than F-type at baseline, D
      type had higher baseline scores on the Unified Parkinson's Disease Rating Scale
      (UPDRS) Part III. Evaluations of motor progression showed that the disease
      duration with motor symptoms was shorter in D-type than F-type. Moreover, the
      survival time was shorter in D-type (6.9 years) than F-type (9.4 years). Cox
      regression analyses revealed that a high UPDRS Part III score at baseline
      contributed to an increased risk of mortality, regardless of the pattern of
      atrophy. CONCLUSIONS: The prognosis is worse for D-type than for those with F
      type. Shorter survival in D-type may be associated with the earlier appearance of
      motor symptoms.

PMID- 28748675
TI  - Does Diabetes Mellitus Influence Carpal Tunnel Syndrome?
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus (DM) has been proposed as a risk factor
      for carpal tunnel syndrome (CTS), but this remains controversial. We investigated
      the association between DM and CTS using both ultrasonography (US) and nerve
      conduction study (NCS) data. METHODS: We analyzed a prospectively recruited
      database of neuromuscular US and medical records of subjects who had undergone
      NCSs and electromyography for symptoms suggestive of CTS. Subjects were assigned
      to the follow groups: Group I, CTS with DM; Group II, CTS without DM; Group III,
      no CTS with DM; and Group IV, no CTS without DM. US cross-sectional area (CSA)
      and NCS measurements at the median nerve (MN) were compared among groups. We used
      a general linear mixed model to adjust for statistically significant covariates.
      RESULTS: The 230 participants comprised 22, 83, 19, and 106 in Groups I-IV,
      respectively. In multivariate analyses, the MN action potential amplitude in
      females was the only variable that was significantly associated with DM
      (p<0.001). Groups with DM tended to have a longer latency, smaller amplitude, and
      lower conduction velocity in the NCSs compared to groups without DM. The measured
      US CSA values did not differ significantly among the groups. CONCLUSIONS: NCS
      measurements of the MN tended to differ between DM and non-DM patients regardless
      of the presence or absence of CTS. However, US did not reveal any statistically
      significant relationship between CTS and DM.

PMID- 28748676
TI  - Relationship between Erectile Dysfunction, Comorbidity, and Parkinson's Disease:
      Evidence from a Population-Based Longitudinal Study.
AB  - BACKGROUND AND PURPOSE: To determine the risk of Parkinson's disease (PD) in
      relation to erectile dysfunction (ED) based on the National Health Insurance
      Research Database in Taiwan. METHODS: We identified 3,153 patients who were newly
      diagnosed with ED between January 1, 2004 and December 31, 2010. A total of
      12,612 randomly selected people without ED served as healthy controls. All of the
      study subjects were followed-up from the index date to the date of PD diagnosis,
      withdrawal from the National Health Insurance program, or the end of 2012
      whichever occurred first. RESULTS: The incidence density rate of PD was 1.52-fold
      higher in the ED cohort than the non-ED cohort (3.44 vs. 1.64 per 1,000 person
      years), with an adjusted hazard ratio (HR) of 1.52 [95% confidence interval
      (CI)=1.09-2.12]. The combined effects on patients with ED and diabetes as well as
      hypertension showed a significant combined association with the PD risk compared
      with patients without ED, counterpart comorbidities, or medication use. The
      adjusted HR of PD for ED was higher for diabetes (2.82, 95% CI=1.42-5.63) and
      hypertension (2.19, 95% CI = 1.35-3.55). CONCLUSIONS: ED leads to an increased
      risk of PD. ED patients with diabetes or hypertension have an elevated risk of
      PD.

PMID- 28748677
TI  - Subjective Evaluation of Mood and Cognitive Functions in a General Neurology
      Clinic: Patients versus Informants.
AB  - BACKGROUND AND PURPOSE: We aimed to determine the correlation between subjective
      evaluations of mood and cognitive functions by patients and informants, and the
      findings of a battery of neuropsychological tests. METHODS: We analyzed 74
      subjects recruited from a general neurology clinic, comprising 37 patients with
      cognitive complaints and 37 informants (either relatives or caregivers in close
      contact with the patients). Four ordinal scales concerning recent memory, verbal
      expression, initiative, and mood were correlated with the findings of a series of
      neuropsychological tests and questionnaires using the tau b coefficient. RESULTS:
      The scores for the patients on the scales were most strongly correlated with
      scores on the 15-item Geriatric Depression Scale (GDS-15), while the scores for
      the informants were most strongly correlated with scores on GDS-15, the Informant
      Questionnaire on Cognitive Decline, and the Functional Activities Questionnaire
      (FAQ). The most significant correlation was between the initiative scale from
      informants and FAQ (tau b=-0.591, p<0.001), and it was the only one that remained
      significant after correcting for multiple testing (p Holm=0.013). CONCLUSIONS:
      Cognitive complaints from patients mainly reflect their mood, whilst informant
      reports mainly reflect both the functional ability and mood of the patients.

PMID- 28748678
TI  - Prevalence of Self-Perceived Snoring and Apnea and Their Association with Daytime
      Sleepiness in Korean High School Students.
AB  - BACKGROUND AND PURPOSE: There has been no nationwide population-based study of
      the prevalence of self-perceived snoring/apnea in Korean adolescents. The purpose
      of this study was to estimate prevalence of self-perceived snoring/apnea in
      Korean high-school students and to evaluate their association with daytime
      sleepiness. METHODS: An online survey was used to investigate 12,672 students at
      75 high schools across the 15 nationwide districts of South Korea. The variables
      were obtained using a self-reported questionnaire. The students answered
      questions about self-perceived snoring/apnea during the past 30 days. Daytime
      sleepiness was measured using a validated Korean version of the Epworth
      Sleepiness Scale, which was modified for adolescents. Covariates were the sex,
      school grade, frequency of self-perceived snoring/apnea, body mass index, sleep
      duration during a school day, and subjective perception of sleep duration.
      RESULTS: The prevalence of self-perceived snoring/apnea was 22.8% (26.4% for
      males vs. 18.8% for females, p<0.001) and 9.2% (10.5% for males vs. 7.7% for
      females, p<0.001). Obesity was significantly associated with self-perceived
      snoring [odds ratio (OR)=2.18, 95% confidence interval (CI)=1.94-2.46] and apnea
      (OR=1.57, 95% CI=1.33-1.86). Multivariate analysis showed that any frequency of
      self-perceived snoring/apnea was significantly associated with excessive daytime
      sleepiness (EDS). The OR of EDS increased significantly with the frequency of
      snoring and apnea. Female, sleep duration of <5 hours during a school day, and
      subjective perceptions of insufficient and considerable sleep durations were also
      significantly associated with EDS. CONCLUSIONS: The prevalence of self-perceived
      snoring/apnea was significantly higher in students who were male and obese.
      Students with self-perceived snoring/apnea exhibited more significant EDS and an
      increased risk of EDS as the frequency of snoring and apnea increased.

PMID- 28748679
TI  - Quality of Anticoagulation with Warfarin in Korean Patients with Atrial
      Fibrillation and Prior Stroke: A Multicenter Retrospective Observational Study.
AB  - BACKGROUND AND PURPOSE: The quality of anticoagulation is critical for ensuring
      the benefit of warfarin, but this has been less well studied in Korean ischemic
      stroke patients with atrial fibrillation (AF). METHODS: This study
      retrospectively analyzed the data of patients who had an AF-related ischemic
      stroke and were treated with long-term warfarin therapy in 16 Korean centers. The
      quality of warfarin therapy was primarily assessed by the time in therapeutic
      range [TTR; international normalized ratio (INR), 2.0-3.0] and additionally by
      the proportion of INR values within the therapeutic range. RESULTS: The long-term
      warfarin-treated cohort comprised 1,230 patients. They were aged 70.1+/-9.7 years
      (mean+/-SD), 42.5% were female, and their CHA2DS2-VASc score was 4.75+/-1.41. The
      TTR analysis included 33,941 INR measurements for 27,487 months: per patients,
      27.6 (SD, 22.4) INR measurements for 22.4 (SD, 12.9) months. The mean TTR of
      individual patients was 49.1% (95% confidence interval, 47.9-50.3%), and the TTR
      quartiles were <34.5, 34.5-49.1, 49.1-64.5%, and >64.5%. None of the 16 centers
      achieved a mean TTR of >60%. Of all INR measurements, 44.6% were within the
      therapeutic range, 41.7% were <2.0, and 13.7% were >3.0. CONCLUSIONS: In Korean
      ischemic stroke patients who had AF, the quality of warfarin therapy was low and
      might be inadequate to effectively prevent recurrent stroke or systemic embolism.

PMID- 28748680
TI  - Factors Associated with Favorable Outcome of Topiramate Migraine Prophylaxis in
      Pediatric Patients.
AB  - BACKGROUND AND PURPOSE: There are few studies that have investigated predictive
      factors related to migraine prophylaxis of which produced inconsistent results.
      The aim of this study was to identify factors that can predict the treatment
      response to topiramate prophylaxis in pediatric patients with migraine. METHODS:
      One hundred and thirteen patients who were older than 7 years and received
      topiramate for at least 3 months were recruited from the Seoul National
      University Bundang Hospital outpatient clinic from 2005 to 2014. A positive
      response was defined as a reduction of more than 50% in the number of migraine
      episodes after topiramate treatment. Proposed predictive factors such as migraine
      characteristics including severity and frequency were assessed, as were other
      data on sex, disease duration, associated symptoms, family history, and
      impairment of daily activities. RESULTS: Seventy patients (61.9%) responded to
      prophylactic treatment with topiramate. Patients who experienced significant
      impairment in daily activities showed significant benefit from the treatment
      (p=0.004). Sex, the severity, frequency, and duration of migraine episodes,
      disease duration, treatment duration, age at onset, and associated symptoms were
      not significantly related to a response to topiramate treatment. CONCLUSIONS:
      Migraine characteristics and associated symptoms were not significantly related
      to a response to topiramate treatment. However, patients with significant
      impairment in daily activities showed significant benefit from the treatment, and
      so prophylactic topiramate treatment should be strongly encouraged in this
      patient group.

PMID- 28748681
TI  - Severe Paraneoplastic Parkinsonism: A Rare Cause Revealing Breast Cancer.

PMID- 28748682
TI  - Extra-Axial Mass in the Foramen Magnum Causing Cervical Compressive Myelopathy as
      a Complication of Rosai-Dorfman Disease.

PMID- 28748684
TI  - Prognostic factors in head and neck melanoma according to facial aesthetic units.
AB  - BACKGROUND: Head and neck melanoma is a clinical challenge. Indeed, cutaneous
      head and neck melanoma shows a worse prognosis in comparison to melanomas of
      other body sites. Although the emphasis on facial cosmetic preservation plays a
      pivotal role in comparison to other body areas, specific facial aesthetic units
      could also play a key role in the prognostic evaluation of the malignancy.
      METHODS: The aim of the current study was to evaluate the general outcome and
      clinicopathological features of head and neck melanoma and to detect prognostic
      differences according to each facial aesthetic unit. The KaplanMeier product was
      used to calculate survival curves, while Cox proportionalhazard regression was
      performed to evaluate the predictive value of each facial aesthetic unit.
      RESULTS: A total of 221 head and neck melanoma patients was included in our
      analysis. In the nasal facial aesthetic unit, we found a high rate of local
      recurrence, which affected significantly disease free survival. The worse
      prognosis was observed in melanoma of the scalp, which showed a greater tendency
      to skip metastases in internal organs. Moreover, we found that scalp showed a low
      incidence of nonmelanoma skin cancers, if compared to other facial aesthetic
      unit, highlighting that the scalp local milieu might play a more prominent role
      in melanoma biology than chronic UV exposition. CONCLUSIONS: Although facial
      aesthetic units have an aesthetic function, they could also play a role in the
      evaluation and followup of melanoma.

PMID- 28748683
TI  - Erratum to: The KMDS-NATION Study: Korean Movement Disorders Society Multicenter
      Assessment of Non-Motor Symptoms and Quality of Life in Parkinson's Disease
      NATION Study Group.
AB  - This corrects the article on p. 393 in vol. 12, PMID: 27819413.

PMID- 28748685
TI  - Skin signs of systemic infections and neoplastic diseases.
AB  - In recent years, emphasis on the physical examination has made way for a plethora
      of laboratory tests and sophisticated imaging diagnostic techniques. In addition,
      we are witnessing an underestimation of dermatology as a specialty around the
      world, which is accepted as an ambulatory specialty on the border of cosmetology
      and beautification. However, recognizing specific cutaneous clinical signs can
      facilitate timely diagnosis of various systemic infections and neoplastic
      diseases. Thus, a skilled dermatologist can play an essential role in the
      multidisciplinary team, involved in the care for systemically ill patients. In
      this article, we will focus on some life threatening systemic infections in which
      the skin changes can be a major clue for the diagnosis. Recent deadly epidemics
      will also be focused. Classic examples of paraneoplastic skin conditions will
      also be provided.

PMID- 28748686
TI  - Invisible dermatoses from the perspective of the dermatopathologist: new
      observations.
AB  - The term "invisible dermatoses" is often used in two different contexts: 1)
      dermatoses which are invisible to the clinician, i.e., diseases with no
      significant clinical features; 2) dermatoses which are invisible to the
      pathologist. These latter comprise a wide spectrum of entities which present with
      definite and obvious clinical features, but subtle or hidden histological
      features and are therefore "invisible" histologically. Diagnosis of such diseases
      represents a great challenge to both the dermatologist and dermatopathologist.
      The list of such diseases, originally comprising only few entities, has been
      gradually expanded over decades and now is a large one. This review focuses on
      the recently expanded spectrum of such diseases, and offers to the
      dermatopathologist a strategy for their diagnosis, based mainly on proper
      awareness, recognition of subtle features, special stains, special investigations
      such as immunofluorescence and histochemistry and proper clinicopathological
      correlation.

PMID- 28748687
TI  - Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction.

PMID- 28748688
TI  - Physical Abuse of Children.

PMID- 28748689
TI  - Physical Abuse of Children.

PMID- 28748690
TI  - Data Authorship as an Incentive to Data Sharing.

PMID- 28748691
TI  - More on Intralymphatic Injection of Autoantigen in Type 1 Diabetes.

PMID- 28748692
TI  - Reductive Activation of C70 Equatorial Carbons and Structurally Characterized C70
      delta-Adduct with Closed [5,6]-Ring Fusion.
AB  - The C70 delta-adducts with closed [5,6]-ring fusion are an important type of
      compound in classifying bond delocalization in the equatorial belt of C70.
      However, the formation of such compounds is severely restricted due to the low
      reactivity of the carbon atoms in the flat equatorial region. Such a restriction
      is lifted when reduced anionic C70 species are used, where the inert equatorial
      carbon atoms are activated.

PMID- 28748693
TI  - All-Polymeric Flexible Transparent Heaters.
AB  - All-polymeric flexible transparent heaters (THs) are demonstrated for the first
      time. Thin films of four poly(3,4-ethylenedioxythiophene) (PEDOT)-based materials
      embedding different dopants exhibit low sheet resistances, down to 57 Omega sq-1
      associated with good transparencies (>87%) and a haze lower than 1%. These
      transparent thin films show excellent heating properties, with high heating rates
      (up to 1.6  degrees C s-1) and steady-state temperatures exceeding 100  degrees C
      when subjected to 12 V bias. Very high areal power densities were also measured,
      reaching almost 10 000 W m-2. The temperature increase is finely fitted to a
      thermal model. It is further demonstrated that these new THs can be efficiently
      integrated for applications in thermochromic displays and visor deicers.

PMID- 28748694
TI  - Bilayered Nanoparticles with Sequential Release of VEGF Gene and Paclitaxel for
      Restenosis Inhibition in Atherosclerosis.
AB  - Complete reendothelialization followed by inhibition of smooth muscle cell (SMC)
      proliferation is considered as an effective therapeutic option to prevent
      restenosis. We have designed poly(lactide-co-glycolide)-loaded bilayered
      nanoparticles (NPs) with the ability to sequentially release vascular endothelial
      growth factor (VEGF)-encoding plasmids from the outer layer and paclitaxel (PTX)
      from the core to promote endothelial regeneration as well as prevent restenosis.
      Comparing with conventional NPs, which release VEGF plasmid and PTX
      simultaneously, we expect that the bilayered NPs could release the VEGF plasmid
      more rapidly, followed by a delayed release of PTX, resulting in an efficient
      VEGF gene transfection, which ideally could promote reendothelialization and
      inhibit excessive SMC growth. Indeed, in the present study, we have observed
      efficient gene transfection using a model plasmid as well as cell growth
      attenuation in vitro using Chinese hamster ovary cells. Therapeutic efficacy of
      the bilayered NPs on restenosis was further evaluated in vivo using a rabbit
      model of atherosclerosis. The bilayered NPs were administered locally via balloon
      angioplasty to the injured aortic wall through perfusion. Twenty-eight days after
      the NP administration, rabbits treated with the bilayered NPs exhibited rapid
      reendothelialization and inhibition of restenosis, as demonstrated by
      histological analysis. Increased level of VEGF and decreased level of C-reactive
      protein, a biological marker that is closely related to atherosclerosis, were
      also observed from animals treated with the bilayered NPs, implicating
      ameliorated atherosclerosis. Our results suggest that the VEGF plasmid-/PTX
      loaded bilayered NPs exert a beneficial impact on atherosclerotic restenosis by
      sequentially releasing VEGF and PTX in vivo.

PMID- 28748695
TI  - Extraction and Quantification of Sinapinic Acid from Irish Rapeseed Meal and
      Assessment of Angiotensin-I Converting Enzyme (ACE-I) Inhibitory Activity.
AB  - Phenolic compounds, including phenolic acids, are known to play a protective role
      against the development of cardiovascular disease. The aim of this work was to
      generate a phenolic acid extract from Irish rapeseed meal, to determine the
      quantity of sinapinic acid (SA) in this fraction and to assess the ability of
      this fraction to inhibit the enzyme angiotensin-I converting enzyme (ACE-I; EC
      3.4.15.1). A crude phenolic extract (fraction 1), free phenolic acid containing
      extract (fraction 2), and an extract containing phenolic acids liberated from
      esters (fraction 3) were generated from Irish rapeseed meal using a
      methanol:acetone:water solvent mixture (7:7:6). The total phenolic content (TPC)
      of each extract was determined and proximate analysis performed to determine the
      fat, moisture, and protein content of these extracts. Nuclear magnetic resonance
      (1H NMR) spectroscopy was used to quantify the level of SA in extract 3, which
      inhibited ACE-I by 91% +/- 0.08 when assayed at a concentration of 1 mg/mL,
      compared to the control, captopril, which inhibited ACE by 97% +/- 0.01 when
      assayed at a concentration of 1 mg/mL.

PMID- 28748696
TI  - Ultrasound Characterization of Microbead and Cell Suspensions by Speed of Sound
      Measurements of Neutrally Buoyant Samples.
AB  - We present an experimental method including error analysis for the measurement of
      the density and compressibility of cells and microbeads; these being the two
      central material properties in ultrasound-based acoustophoretic applications such
      as particle separation, trapping, and up-concentration. The density of the
      microparticles is determined by using a neutrally buoyant selection process that
      involves centrifuging of microparticles suspended in different density solutions,
      CsCl for microbeads and Percoll for cells. The speed of sound at 3 MHz in the
      neutrally buoyant suspensions is measured as a function of the microparticle
      volume fraction, and from this the compressibility of the microparticles is
      inferred. Finally, from the obtained compressibility and density, the acoustic
      scattering coefficients and contrast factor of the microparticles are determined,
      and in a sensitivity analysis, the impact of the measurement errors on the
      computed acoustic properties is reported. The determination of these parameters
      and their uncertainties allow for accurate predictions of the acoustophoretic
      response of the microparticles. The method is validated by determining the
      density (0.1-1% relative uncertainty) and compressibility (1-3% relative
      uncertainty) of previously well-characterized polymer microbeads and subsequently
      applied to determine the density (0.1-1% relative uncertainty), compressibility
      (1% relative uncertainty), scattering coefficients, and acoustic contrast factors
      for nonfixed and fixed cells, such as red blood cells, white blood cells, DU-145
      prostate cancer cells, MCF-7 breast cancer cells, and LU-HNSCC-25 head and neck
      squamous carcinoma cells in phosphate buffered saline. The results show agreement
      with published data obtained by other methods.

PMID- 28748697
TI  - Portable Lock-in Amplifier-Based Electrochemical Method to Measure an Array of 64
      Sensors for Point-of-Care Applications.
AB  - We present a portable lock-in amplifier-based electrochemical sensing system. The
      basic unit (cluster) consists of four electrochemical cells (EC), each containing
      one pseudoreference electrode (PRE) and one working electrode (WE). All four ECs
      are simultaneously interrogated, each at different frequencies, with square wave
      pulses superposed on a sawtooth signal for cyclic voltammetry (CV). Lock-in
      amplification provides independent read-out of four signals, with excellent noise
      suppression. We expanded a single cluster system into an array of 16 clusters by
      using electronic switches. The chip with an array of ECs was fabricated using
      planar technology with a gap between a WE and a PRE of ~2 MUm, which results in
      partial microelectrode-type behavior. The basic electrode characterization was
      performed with the model case using a ferricyanide-ferrocyanide redox couple
      (Fe2+/Fe3+) reaction, performing CV and differential pulse voltammetry (DPV). We
      then used this system to perform cyclic lock-in voltammetry (CLV) to measure
      concurrently responses of the four ECs. We repeated this method with all 64 ECs
      on the chip. The standard deviation of a peak oxidation and reduction current in
      a single channel consisting of 13 ECs was ~7.46% and ~5.6%, respectively. The
      four-EC configuration in each measured spot allows determination of nonperforming
      ECs and, thus, to eliminate potential false results. This system is built in a
      portable palm-size format suitable for point-of-care applications. It can perform
      either individual or multiple measurements of active compounds, such as
      biomarkers.

PMID- 28748698
TI  - Band Gap Engineering of Titania Film through Cobalt Regulation for Oxidative
      Damage of Bacterial Respiration and Viability.
AB  - Biomaterial-related bacterial infections cause patient suffering, mortality, and
      extended periods of hospitalization and impose a substantial burden on medical
      systems. In this context, understanding the interactions between nanomaterials
      and bacteria is clinically significant. Herein, TiO2-based heterojunctions,
      including Co-TiO2, CoO-TiO2, and Co3O4-TiO2, were first designed by optimizing
      magnetron sputtering to establish a platform to explore the interactions between
      nanomaterials and bacteria. We found that the energy band bending and band gap
      narrowing were effectively promoted at the contact interface of the
      heterojunctions, which have the ability to induce abiotic reactive oxygen species
      formation. Using methicillin-resistant Staphylococcus aureus and Staphylococcus
      epidermidis, in vitro studies showed that the heterojunctions of Co-TiO2, CoO
      TiO2, and especially Co3O4-TiO2 can effectively downregulate the expression
      levels of bacterial respiratory genes and cause oxidative damage to bacterial
      membrane respiration and viability. As a result, the surfaces of the
      heterojunctions possess a favorable antiadherent bacterial activity. Moreover,
      using an osteomyelitis model, the preclinical study on rats further confirmed the
      favorable anti-infection effect of the elaborately designed heterojunctions
      (especially Co3O4-TiO2). We hope this study can provide new insights into the
      surface antibacterial design of biomaterials using energy band engineering for
      both basic research and clinical needs. Meanwhile, this attempt may also
      contribute to expanding the biomedical applications of cobalt-based nanoparticles
      for the treatment of antibiotic-resistant infections.

PMID- 28748699
TI  - 1,3-syn-Diaxial Repulsion of Typical Protecting Groups Used in Carbohydrate
      Chemistry in 3-O-Substituted Derivatives of Isopropyl d-Idopyranosides.
AB  - The strength of 1,3-syn-diaxial repulsion was evaluated for main types of
      protecting groups (alkyl, silyl, and acyl) usually used in carbohydrate
      chemistry. As molecular probes for this study, derivatives of isopropyl 2-O
      benzyl-4,6-O-benzylidene-alpha-d-idopyranoside bearing allyl, acetyl, and tert
      butyldiphenylsilyl (TBDPS) protecting groups at O-3 were prepared from p
      methoxyphenyl d-galactopyranoside. The equilibrium between OS2 and 4C1
      conformations in these compounds was investigated using 3JH,H and 3JC,H coupling
      constants that were determined from 1D 1H NMR and 2D J-resolved HMBC spectra in
      various solvents. The analysis of the corresponding coupling constants calculated
      using DFT/B3LYP/pcJ-1 approximation applied to conformations optimized at
      DFT/B3LYP/6-311++G** level supported the investigation. Proportions of conformers
      in the equilibrium revealed the highest repulsion between the 3-allyloxy group
      and the isopropoxy aglycon and its dependence on the solvent polarity.
      Differences in the conformational behavior of 3-O-allyl and 3-O-acetyl-alpha-d
      idopyranoside derivatives complied with the notion that higher electron density
      on O-3 increased 1,3-syn-diaxial repulsion. 3-O-TBDPS derivative existed mainly
      in 4C1 conformation. The attenuation of the 1,3-syn-diaxial repulsive interaction
      indicates that TBDPS has stereoelectronic properties that may have significance
      in context of fixing unnatural pyranoside conformation with the help of silyl
      groups but have been disregarded until now.

PMID- 28748700
TI  - Wittig Cyclization of omega-Hydroxy Hemiacetals: Synthesis of (+)-Aspicilin.
AB  - The polyhydroxylated 18-membered lichen macrolide (+)-aspicilin was synthesized
      in 12 steps and 17% yield (longest linear sequence) starting from d-mannose and
      (S)-propylene oxide as the source of the stereogenic centers. Key steps were a
      palladium-catalyzed Csp3X-Csp3ZnX Negishi cross-coupling affording an omega
      hydroxy hemiacetal which was macrocyclized via a domino addition-Wittig
      olefination reaction with the cumulated ylide Ph3PCCO. This synthetic approach
      also allowed a regioselective glycosylation of 6-OH of aspicilin with d
      desosamine, a quick entry to chimeric macrolides with potential antibiotic
      activity.

PMID- 28748701
TI  - Mesoporous ZrO2 Nanoframes for Biomass Upgrading.
AB  - The rational design and preparation of a high-performance catalyst for biomass
      upgrading are of great significance and remain a great challenge. In this work,
      mesoporous ZrO2 nanoframe, hollow ring, sphere, and core-shell nanostructures
      have been developed through a surfactant-free route for upgrading biomass acids
      into liquid alkane fuels. The obtained ZrO2 nanostructures possess well-defined
      hollow features, high surface areas, and mesopores. The diversity of the
      resultant ZrO2 nanostructures should arise from the discrepant hydrolysis of two
      different ligands in zirconocene dichloride (Cp2ZrCl2) as the zirconium
      precursor. The time-dependent experiments indicate that Ostwald ripening and salt
      crystal-template formation mechanisms should account for hollow spheres and
      nanoframes, respectively. Impressively, compared with the hollow sphere,
      commercial nanoparticle, and the ever-reported typical results, the ZrO2
      nanoframe-promoted Ni catalyst exhibits greatly enhanced catalytic activity in
      the upgrading of biomass acids to liquid alkane fuels, which should be ascribed
      to the hollow feature, large active surface area, highly dispersed Ni, and strong
      metal-support interactions arising from the structural advantages of nanoframes.
      The nanoframes also possess excellent solvothermal and thermal stability. Our
      findings here can be expected to offer new perspectives in material chemistry and
      ZrO2-based catalytic and other applications.

PMID- 28748702
TI  - Monte Carlo Study of a Planar Electric Double Layer Formed by Ions with Off
      Center Charge.
AB  - Grand canonical Monte Carlo simulation results are reported for an electric
      double layer (EDL) modeled by a planar charged hard wall, hard sphere cations
      with an off-center charge, and spherical anions with a charge at the center of
      the sphere. The ion charge numbers are Z+ = +1 and Z- = -1, and the diameter, d,
      of a hard sphere is the same for anions and cations. The ions are immersed in a
      solvent mimicked by a continuum dielectric medium at standard temperature. The
      results are obtained for three values of charge displacement, s+0 = d/16, d/4,
      7d/16 from the center of the sphere and the following electrolyte concentrations:
      0.5, 1.0, 2.0, and 3.0 M. The profiles of electrode-ion singlet distributions,
      cation reduced charge density, angular function, and mean electrostatic potential
      are reported for an electrode surface charge density sigma = -0.30 C m-2, whereas
      the electrode potential and the differential capacitance of EDL are shown as
      functions of the electrode charge density varying from -1.00 to +1.00 C m-2. At
      negative electrode charges and with increasing values of the charge separation,
      the differential capacitance curve rises. As the electrolyte concentration
      increases, the shape of the differential capacitance curve changes from that of a
      minimum surrounded by two maxima into that of a distorted single maximum.

PMID- 28748703
TI  - Time-Resolved Vibrational Spectroscopy of Polytetrafluoroethylene Under Laser
      Shock Compression.
AB  - Shock-wave-induced high pressure and nanosecond time-resolved Raman spectroscopic
      experiments were performed to examine the dynamic response of
      polytetrafluoroethylene (PTFE) in confinement geometry targets. Time-resolved
      Raman spectroscopy was used to observe the pressure-induced molecular and
      chemical changes on nanosecond time scale. Raman spectra were measured as a
      function of shock pressure in the 1.2-2.4 GPa range. Furthermore, the symmetric
      stretching mode at 729 cm-1 of CF2 was compared to corresponding static high
      pressure measurements carried out in a diamond anvil cell, to see if any general
      trend can be established. The symmetric stretching mode of CF2 at 729 cm-1 is the
      most intense Raman transition in PTFE and is very sensitive to change in
      pressure. Therefore, it can also be utilized as a pressure gauge for large
      amplitude shock wave compression experiments. A maximum blueshift of 12 cm-1 for
      the 729 cm-1 vibrational mode has been observed for the present experimental
      pressure range. A comparative study on the similarities and differences from the
      earlier work has been done in detail. One-dimensional radiation hydrodynamic
      simulations were performed to validate our shock compression results and are in
      very good agreement.

PMID- 28748704
TI  - Understanding the experiences of married Southern African women in protecting
      themselves from HIV/AIDS: a systematic review and meta-synthesis.
AB  - BACKGROUND: Whilst marriage has been repeatedly identified in the literature as
      an HIV risk factor amongst Southern African women, not much is known about
      women's perception of their role, experiences and strategies used to address HIV
      risks in the context of a marriage. AIMS: The aim of the study was to synthesise
      perceptions, experiences and strategies of married Southern African women in the
      prevention of HIV. METHODS: A systematic review of qualitative studies was
      conducted. Three electronic databases (Medline, Cinahl and PsycINFO) were
      systematically searched to identify relevant literature. The meta-synthesis
      process followed Sandelowski and Barroso's [2007. Handbook for Synthesizing
      Qualitative Research. Springer Publishing Company] recommendations. RESULTS: Of 7
      609 papers, 15 were included in the review. The quality of the included studies
      was variable. In the final synthesis stage, three broad analytic themes emerged:
      contextual background, cues to preventive behaviour, and HIV prevention
      strategies. IMPLICATIONS: Findings were used to develop a conceptual framework
      for studying HIV/AIDS prevention experiences of married Southern African women.

PMID- 28748705
TI  - The Comprehensive Glucose Pentagon: A Glucose-Centric Composite Metric for
      Assessing Glycemic Control in Persons With Diabetes.
AB  - BACKGROUND: Composite metrics have the potential to provide more complete and
      clinically useful information about glycemic control than traditional individual
      metrics such as hemoglobin A1C, %/time/area under curve of hypoglycemia and
      hyperglycemia. METHODS: Using five key metrics that are derived from continuous
      glucose monitoring, we developed a new, multicomponent composite metric, the
      Comprehensive Glucose Pentagon (CGP) that demonstrates glycemic control both
      numerically and visually. Two of its axes are composite metrics-the intensity of
      hypoglycemia and intensity of hyperglycemia. This approach eliminates the use of
      the surrogate marker, hemoglobin A1C (A1C), and replaces it with glucose-centric
      metrics. RESULTS: We reanalyzed the data from two randomized control trials, the
      STAR 3 and ASPIRE In-Home studies using the CGP. It provided new insights into
      the effect of sensor-augmented pumping (SAP) in the STAR 3 trial and sensor
      integrated pumping with low-glucose threshold suspend (SIP+TS) in the ASPIRE In
      Home trial. CONCLUSIONS: The CGP has the potential to enable health care
      providers, investigators and patients to better understand the components of
      glycemic control and the effect of various interventions on the individual
      elements of that control. This can be done on a daily, weekly, or monthly basis.
      It also allows direct comparison of the effects on different interventions among
      clinical trials which is not possible using A1C alone. This new composite metric
      approach requires validation to determine if it provides a better predictor of
      long-term outcomes than A1C and/or better predictor of severe hypoglycemia than
      the low blood glucose index (LBGI).

PMID- 28748706
TI  - The Development of New Composite Metrics for the Comprehensive Analytic and
      Visual Assessment of Hypoglycemia Using the Hypo-Triad.
AB  - BACKGROUND: Quantifying hypoglycemia has traditionally been limited to using the
      frequency of hypoglycemic events during a given time interval using data from
      blood glucose (BG) testing. However, continuous glucose monitoring (CGM) captures
      three parameters-a Hypo-Triad-unavailable with BG monitoring that can be used to
      better characterize hypoglycemia: area under the curve (AUC), time (duration of
      hypoglycemia), and frequency of daily episodes below a specified threshold.
      METHODS: We developed two new analytic metrics to enhance the traditional Hypo
      Triad of CGM-derived data to more effectively capture the intensity of
      hypoglycemia (IntHypo) and overall hypoglycemic environment called the
      "hypoglycemia risk volume" (HypoRV). We reanalyzed the CGM data from the ASPIRE
      In-Home study, a randomized, controlled trial of a sensor-integrated pump system
      with a low glucose threshold suspend feature (SIP+TS), using these new metrics
      and compared them to standard metrics of hypoglycemia. RESULTS: IntHypo and
      HypoRV provide additional insights into the benefit of a SIP+TS system on
      glycemic exposure when compared to the standard reporting methods. In addition,
      the visual display of these parameters provides a unique and intuitive way to
      understand the impact of a diabetes intervention on a cohort of subjects as well
      as on individual patients. CONCLUSION: The IntHypo and HypoRV are new and
      enhanced ways of analyzing CGM-derived data in diabetes intervention studies
      which could lead to new insights in diabetes management. They require validation
      using existing, ongoing, or planned studies to determine whether they are
      superior to existing metrics.

PMID- 28748707
TI  - Staphylococcus epidermidis: a major player in bacterial sepsis?

PMID- 28748708
TI  - Deciphering the significance of the T-cell response to Staphylococcus aureus.

PMID- 28748709
TI  - Aging Perceptions in Older Gay and Bisexual Men in Portugal: A Qualitative Study.
AB  - Aims and Objectives The purpose of this study was to explore the perceptions
      toward aging among Portuguese gay and bisexual men over 60 years old. Background
      Despite the growth of the older population, and the increased visibility and
      acceptance of lesbian, gay, and bisexual people in Western countries, the
      experience of aging in older gay and bisexual men is only beginning to be
      understood. Design We used a qualitative research methodology, based on critical
      gerontology, for establishing research questions and to identify the perspectives
      on the aging process in older gay and bisexual individuals. Methods We used a
      structured electronic inquiry with 25 gay and bisexual men over 60 years of age
      from Portugal. Data were analyzed using thematic analysis to help identify
      repeated patterns of meaning in the data set. Results The recurrent themes in the
      narratives of the aging experiences of the participants in the study were as
      follows: positive perceptions of aging, negative perceptions of aging, coping
      with being a gay/bisexual man and family ties, professional care,
      homophobia/discrimination, relationships and social support, intergenerational
      differences, mediating role of sexual orientation, sociopolitical changes, and
      personal characteristics. Conclusion Analysis of perceptions about the aging
      process in older gay and bisexual men emphasized the desire for normalization in
      the social awareness of sexual orientation. It is important to continue doing
      research on this topic and disseminate this information among professionals who
      work with older lesbian, gay, and bisexual people so that they may better
      understand how they can meet the specific needs of this population.

PMID- 28748710
TI  - National Suicide Prevention, Local Mental Health Resources, and Suicide Rates in
      Japan.
AB  - BACKGROUND: Suicide rates in Japan are relatively high in OECD countries. A
      national fund to help local authorities implement suicide prevention programs was
      launched in 2009. The national suicide prevention project was transferred from
      the Cabinet Office to the Ministry of Health, Labor, and Welfare on April 2016,
      with a greater focus on mental health promotion by local governments. AIMS: The
      aim of the present study was to (a) identify local authorities' implementation of
      suicide prevention programs in terms of local health policies, and (b) examine
      the associations between local health resources and suicide rates in Japan.
      METHOD: We investigated the types of programs implemented under the fund, and
      correlations with authorities' sociodemographic characteristics and mental health
      and welfare resources. RESULTS: A majority of authorities implemented general
      suicide prevention programs. More focused programs addressing issues such as
      mental health in the workplace, alcohol problems, and attempted suicide were less
      frequently implemented. There were significantly fewer suicides in health regions
      with a higher ratio of psychiatrists to residents or a lower ratio of psychiatric
      beds. LIMITATIONS: A causal relationship between suicide rates and
      characteristics of local authorities cannot be inferred from the data.
      CONCLUSION: A community mental health system that operated in parallel to the
      current system may result in fewer inpatients and a reduction in Japan's suicide
      rate.

PMID- 28748711
TI  - Augmenting Suture-Button Fixation for Maisonneuve Injuries With Fibular
      Shortening: Technique Tip.

PMID- 28748712
TI  - Association between US features of primary tumor and axillary lymph node
      metastasis in patients with clinical T1-T2N0 breast cancer.
AB  - Background Most patients with early-stage breast cancer have clinically negative
      lymph nodes (LNs). However, 15-20% of patients have axillary nodal metastasis
      based on the sentinel LN biopsy. Purpose To assess whether ultrasound (US)
      features of a primary tumor are associated with axillary LN metastasis in
      patients with clinical T1-T2N0 breast cancer. Material and Methods This
      retrospective study included 138 consecutive patients (median age = 51 years; age
      range = 27-78 years) who underwent breast surgery with axillary LN evaluation for
      clinically node-negative T1-T2 breast cancer. Three radiologists blinded to the
      axillary surgery results independently reviewed the US images. Tumor distance
      from the skin and distance from the nipple were determined based on the US
      report. Association between US features of a breast tumor and axillary LN
      metastasis was assessed using a multivariate logistic regression model after
      controlling for clinicopathologic variables. Results Of the 138 patients, 28
      (20.3%) had nodal metastasis. At univariate analysis, tumor distance from the
      skin ( P = 0.019), tumor size on US ( P = 0.023), calcifications ( P = 0.036),
      architectural distortion ( P = 0.001), and lymphovascular invasion ( P = 0.049)
      were associated with axillary LN metastasis. At multivariate analysis, shorter
      skin-to-tumor distance (odds ratio [OR] = 4.15; 95% confidence interval [CI] =
      1.01-16.19; P = 0.040) and masses with associated architectural distortion (OR =
      3.80; 95% CI = 1.57-9.19; P = 0.003) were independent predictors of axillary LN
      metastasis. Conclusion US features of breast cancer can be promising factors
      associated with axillary LN metastasis in patients with clinically node-negative
      early-stage breast cancer.

PMID- 28748714
TI  - Correction to: Reimschisel T, et al., A systematic review of the published
      literature on team-based learning in health professions education.

PMID- 28748715
TI  - Rate of bleeding-related episodes in elderly patients with primary immune
      thrombocytopenia: a retrospective cohort study.
AB  - OBJECTIVE: Immune thrombocytopenia (ITP) is characterized by low platelet counts
      and a tendency toward increased bleeding and bruising. We aimed to describe
      bleeding frequency and use of rescue ITP therapy to treat or prevent bleeding in
      elderly ITP patients in a real-world setting. METHODS: Using Medicare 20% sample
      data, 2007-2012, we identified elderly (ages >=67 years) Medicare fee-for-service
      enrollees diagnosed with primary ITP between 1 January 2009 and 30 September
      2012. Bleeding-related episodes (BREs) were defined as >=1 bleeding event or use
      of ITP therapies commonly considered for rescue or emergency therapy. BRE rates
      were examined for the cohort overall, by time since ITP onset, and by splenectomy
      status. Patients were followed from ITP onset until the earliest of death,
      disenrollment from fee-for-service coverage, or 31 December 2012. RESULTS: We
      identified 3007 elderly patients diagnosed with primary ITP (mean [SD] age: 79.6
      [7.5] years; 55% female); 2178 (72%) experienced at least one BRE (8867 BREs); 92
      (3%) underwent splenectomy. Nearly half of BREs were defined by rescue therapy
      use alone. The overall rate was 1.72 BREs per patient-year (95% CI; 1.68-1.75);
      rates were higher during the first 3 months after ITP onset and after
      splenectomy. CONCLUSION: Elderly ITP patients experienced about two BREs per
      patient-year after ITP onset. Most patients experienced at least one BRE. These
      real-world results demonstrate the importance of examining both bleeding and use
      of rescue or emergency ITP therapy in the assessment of disease burden in elderly
      patients with ITP.

PMID- 28748713
TI  - QbD for pediatric oral lyophilisates development: risk assessment followed by
      screening and optimization.
AB  - OBJECTIVE: This study proposed the development of oral lyophilisates with respect
      to pediatric medicine development guidelines, by applying risk management
      strategies and DoE as an integrated QbD approach. METHODS: Product critical
      quality attributes were overviewed by generating Ishikawa diagrams for risk
      assessment purposes, considering process, formulation and methodology related
      parameters. Failure Mode Effect Analysis was applied to highlight critical
      formulation and process parameters with an increased probability of occurrence
      and with a high impact on the product performance. To investigate the effect of
      qualitative and quantitative formulation variables D-optimal designs were used
      for screening and optimization purposes. RESULTS: Process parameters related to
      suspension preparation and lyophilization were classified as significant factors,
      and were controlled by implementing risk mitigation strategies. Both quantitative
      and qualitative formulation variables introduced in the experimental design
      influenced the product's disintegration time, mechanical resistance and
      dissolution properties selected as CQAs. The optimum formulation selected through
      Design Space presented ultra-fast disintegration time (5 seconds), a good
      dissolution rate (above 90%) combined with a high mechanical resistance (above
      600 g load). CONCLUSIONS: Combining FMEA and DoE allowed the science based
      development of a product with respect to the defined quality target profile by
      providing better insights on the relevant parameters throughout development
      process. The utility of risk management tools in pharmaceutical development was
      demonstrated.

PMID- 28748716
TI  - Late urinary morbidity and quality of life after radical prostatectomy and
      salvage radiotherapy for prostate cancer.
AB  - OBJECTIVE: There is a paucity of knowledge of long-term urinary morbidity in
      patients treated for prostate cancer (PCa) with radical prostatectomy (RP) and
      salvage radiotherapy (SRT). Improved long-term survival calls for heightened
      awareness of late effects from radiotherapy after RP. The purpose of this study
      was to assess late urinary morbidity and its potential impact on quality of life
      (QoL) in patients treated with RP plus SRT compared with patients treated with RP
      alone. MATERIALS AND METHODS: Long-term morbidity and QoL were evaluated using a
      cross-sectional design with validated questionnaires in urinary morbidity [Danish
      Prostatic Symptom Score (DAN-PSS)] and QoL [European Organisation for Research
      and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)].
      Included were a total of 227 patients treated with SRT and 192 treated with RP in
      the periods 2006-2010 and 2005-2007, respectively. RESULTS: Weak stream,
      straining, frequency and nocturia were significantly more prevalent in patients
      treated with RP + SRT than in patients treated with RP alone. Patients treated
      with RP + SRT generally suffered from more severe urinary symptoms. The QoL
      scores of the two treatment groups were not statistically significantly
      different, but a high level of urinary morbidity was significantly related to
      decreased QoL (p = 0.000). CONCLUSIONS: Patients treated with SRT have a higher
      rate of urinary morbidity than do patients treated with RP alone. Severe urinary
      morbidity was significantly related to decreased QoL, but did not differ between
      the two treatment groups.

PMID- 28748717
TI  - In response to "Balancing the risks and benefits of medication organizers".

PMID- 28748718
TI  - Diabetes drugs and the incidence of solid cancers: a survey of the current
      evidence.
AB  - INTRODUCTION: The evaluation of the relationship between the use of antidiabetic
      drug and the occurrence of cancer is extremely challenging, both from the
      clinical and pharmacoepidemiological standpoint. This narrative review described
      the current evidence supporting a relationship between the use of antidiabetic
      drugs and the incidence of solid cancers. Areas covered: Data from
      pharmacoepidemiological studies on cancer incidence were presented for the main
      antidiabetic drugs and drug classes, including human insulin and insulin
      analogues, metformin, sulfonylureas, glinides, alpha-glucosidase inhibitors,
      thiazolidinediones, incretin mimetics, and sodium glucose co-transporter 2
      inhibitors. The relationship between the use of antidiabetics and the incidence
      of solid cancer was described in strata by any cancer and by organ-specific
      cancer and by drug and by drug classes. Information supporting biological
      evidence and putative mechanisms were also provided. Expert opinion: The history
      of exploration of the relationship between antidiabetic drugs and the risk of
      solid cancers has showed several issues. Unrecognized biases and
      misinterpretations of study results have had important consequences that delayed
      the identification of actual risk and benefits of the use of antidiabetic drugs
      associated with cancer occurrence or progression. The lesson learned from the
      past should address the future research in this area, since in the majority of
      cases findings are controversial and confirmatory studies are warranted.

PMID- 28748719
TI  - Synthesis of potential HIV integrase inhibitors inspired by natural polyphenol
      structures.
AB  - Drawing inspiration from the structural features of some natural polyphenols, the
      synthesis of two different model compounds as potential inhibitors of HIV
      integrase (IN) has been described. The former was characterised by a diketo acid
      (DKA) bioisostere, such as a beta-hydroxycarbonyl moiety, between two fragments
      containing aromatic groups, while in the latter an epoxide linked two
      polyoxygenated aromatic residues. The moieties present in the structures are
      thought to function by chelating divalent metal ions on the enzyme catalytic
      site. Overall, 10 compounds were prepared and some of that submitted to molecular
      modelling studies (to investigate their interactions with the active site of IN),
      to metal titration studies (to detect their chelating capability) and to
      biological assays.

PMID- 28748720
TI  - Blunting of cardioprotective actions of estrogen in female rodent heart linked to
      altered expression of cardiac tissue chymase and ACE2.
AB  - BACKGROUND: Diastolic dysfunction develops in response to hypertension and
      estrogen (E2) loss and is a forerunner to heart failure (HF) in women. The
      cardiac renin-angiotensin system (RAS) contributes to diastolic dysfunction, but
      its role with respect to E2 and blood pressure remain unclear. METHODS: We
      compared the effects of ovariectomy (OVX) or sham surgery on the cardiac RAS,
      left ventricular (LV) structure/function, and systemic/intracardiac pressures of
      spontaneously hypertensive rats (SHRs: n = 6 intact and 6 OVX) and age-matched
      Wistar-Kyoto (WKY: n = 5 intact and 4 OVX) controls. RESULTS: WKY rats were more
      sensitive to OVX than SHRs with respect to worsening of diastolic function, as
      reflected by increases in Doppler-derived filling pressures (E/e') and reductions
      in myocardial relaxation (e'). This pathobiologic response in WKY rats was
      directly linked to increases in cardiac gene expression and enzymatic activity of
      chymase and modest reductions in ACE2 activity. No overt changes in cardiac RAS
      genes or activities were observed in SHRs, but diastolic function was inversely
      related to ACE2 activity. CONCLUSION: Endogenous estrogens exert a more
      significant regulatory role upon biochemical components of the cardiac RAS of WKY
      versus SHRs, modulating the lusitropic and structural components of its
      normotensive phenotype.

PMID- 28748721
TI  - Real-world costs and outcomes in metastatic renal cell carcinoma patients treated
      with targeted therapies: a cohort study from the French health insurance
      database.
AB  - OBJECTIVES: The objective of this study was to describe treatment patterns,
      survival, healthcare use and costs in patients with metastatic renal cell
      carcinoma (mRCC) in a real-world setting. RESEARCH DESIGN AND METHODS: We used
      the National Health Insurance (NHI) claims database for the Ile-de-France region
      to perform a retrospective cohort analysis of patients with mRCC treated by a
      first-line targeted therapy. Treatment naive patients were identified combining
      the 10th revision of the International Classification of Diseases (ICD-10) codes
      (C64 & C77-C79) and a first prescription of targeted therapies. Descriptive
      analyses were performed on treatment patterns and patients' characteristics.
      Progression free survival (PFS) and overall survival (OS) were determined using
      Kaplan-Meier actuarial survival analysis. All healthcare resource use and costs
      were estimated on a per patient per month (PPPM) basis (?2016). RESULTS: A total
      of 327 treatment naive patients with mRCC were included. Median follow-up was
      13.4 months. Sunitinib accounted for 73% of first-line treatments. The most
      frequently observed treatment sequence for the first two lines was sunitinib
      everolimus (16%; n = 137) and for the first three lines sunitinib-everolimus
      axitinib (20%; n = 49). First-line PFS for sunitinib, everolimus, pazopanib,
      sorafenib and other was 8.7, 6.2, 10.7, 5.7 and 11.2 months, respectively. Median
      OS for patients treated by first-line sunitinib, everolimus, pazopanib, sorafenib
      and other was respectively 14.7, 8.1, 21.1, 8.9 and 14.0 months. From the NHI's
      perspective, the mean PPPM was ?5546. The average PPPM in pre-progression was
      ?5597 compared to ?5541 beyond progression of the disease. Oral targeted
      therapies accounted for 53% of the total PPPM. CONCLUSION: This descriptive study
      showed that the economic burden of mRCC is substantial with oral targeted
      therapies accounting for 53% of the PPPM. OS and PFS in real life are poorer than
      observed in clinical trials.

PMID- 28748722
TI  - Gallium-68 prostate-specific membrane antigen positron emission
      tomography/computed tomography for staging of high-risk prostate cancer.

PMID- 28748723
TI  - Applying Positive Deviance for Improving Compliance to Adolescent Anemia Control
      Program in Tribal Communities of India.
AB  - BACKGROUND: Positive deviance (PD) is an asset-based social and behavior change
      communication strategy, utilizing successful outliers within a specific context.
      It has been applied to tackling major public health problems but not adolescent
      anemia. OBJECTIVE: The study, first of its kind, used PD to improve compliance to
      adolescent anemia control program in Jharkhand, India, where anemia prevalence in
      adolescent girls is 70%, and program compliance is low. METHODS: With leadership
      of state government, the study was designed and implemented by a
      multidisciplinary 42 member PD team, in Khunti district, in 2014. Participatory
      appraisals were undertaken with 434 adolescent girls, 18 frontline workers, 15
      teachers, and 751 community leaders/parents/relatives. Stakeholders were
      interviewed to identify positive deviants and PD determinants across 17 villages.
      RESULTS: Perceived benefits of iron folic acid tablet and nutritional care during
      adolescence are low. Positive deviants exist among adolescent girls (26 of 434),
      villages (2 of 17), and schools (2 of 17). Positive deviant adolescent girls
      consumed variety of iron-rich foods and in higher frequency, consumed iron folic
      acid tablets, and practiced recommended personal hygiene behaviors. Deviant
      practices in schools included supervision of students during tablet distribution
      among others. CONCLUSION: Government-led PD approach uncovered local solutions
      and provided a forum for government functionaries to listen to and dialogue with,
      and an opportunity to adapt the program according to the needs of the affected
      communities, who are missing partners in program design and management.

PMID- 28748724
TI  - Acid-base and electrolyte disorders associated with the use of antidiabetic
      drugs.
AB  - INTRODUCTION: The use of antidiabetic drugs is expected to substantially increase
      since diabetes mellitus incidence rises. Currently used antidiabetic drugs have a
      positive safety profile, but they are associated with certain acid-base and
      electrolyte abnormalities. The aim of the review is to present the current data
      regarding the antidiabetic drugs-associated acid-base and electrolyte
      abnormalities. Areas covered: Sodium-glucose cotransporter 2 (SGLT2) inhibitors
      have been linked with the scarce, but serious, complication of euglycemic
      diabetic ketoacidosis, as well as with an increase in serum potassium, magnesium
      and phosphorus levels. Metformin use has been associated with the development of
      lactic acidosis, although many studies have doubt the direct link with this
      serious complication. Additionally, metformin in some studies has been linked
      with a decrease in serum magnesium levels. Insulin administration is associated
      with a reduction in serum potassium, magnesium and phosphorus concentration,
      along with reduced renal magnesium excretion. Pioglitazone is associated with an
      increase in serum magnesium levels. Current data regarding the pathophysiological
      mechanisms, precipitants, risk factors and presentation of the above
      abnormalities are discussed in the present review. Expert opinion: Clinicians
      should choose appropriately between antidiabetic drugs based not only on their
      hypoglycemic efficacy and effects on cardiovascular risk but also based on the
      patient's specific risk to develop acid-base or electrolyte derangements.

PMID- 28748725
TI  - Recent Trends in the Prescribing of ADHD Medications in Canadian Primary Care.
AB  - OBJECTIVE: The aim of this study was to describe the prevalence and incidence of
      ADHD medication prescribing, by age and gender, from 2005 to 2015 in Canadian
      primary care. METHOD: A population-based retrospective cohort study was conducted
      to evaluate the prescribing of ADHD medications between 2005 and 2015 using
      electronic medical record data. Yearly prevalence and incidence of ADHD
      medication prescribing were calculated for preschoolers (up to 5 years old),
      school-aged children (6-17 years old), and adults (18-65 years old) along with a
      description of the types of ADHD medications prescribed between 2005 and 2015.
      RESULTS: Between 2005 and 2015, there was a 2.6-fold increase in the prevalence
      of ADHD medication prescribing to preschoolers, a 2.5-fold increase in school
      aged children, and a fourfold increase in adults. There was a corresponding rise
      in incidence of prescribing although this rise was moderate and estimates were
      much lower compared with prevalence. The most commonly prescribed medication was
      Methylphenidate (65.0% of all ADHD medications prescribed). CONCLUSION: Although
      the prevalence of ADHD has remained stable over time, this study found an
      increase in the prescribing of ADHD medications in all age groups between 2005
      and 2015. Incidence of new prescriptions was small relative to prevalence,
      suggesting that longer term treatments are being adopted.

PMID- 28748726
TI  - Natural products for human health: an historical overview of the drug discovery
      approaches.
AB  - Natural products (NPs) are secondary metabolites produced and used by organisms
      for defending or adapting purposes. These molecules were naturally selected
      during thousands of years to improve the specificity and cover a very wide range
      of functions, depending on the origin, the habitat and the specific activity
      carried out in the organism of origin. Due to these intrinsic features, NPs have
      been used as healing agents since thousands of years and still today continue to
      be the most important source of new potential therapeutic preparations.The
      purpose of this review is to provide information about the historical evolution
      of the NPs investigation methods, focusing attention on the relative
      benefit/problems emerged after the improvement of the scientific investigations
      about them, especially over the last two centuries. Taken together, the reported
      information lead to the central role of NPs in the future of drug development for
      human needs.

PMID- 28748727
TI  - Silk fabric dyed with extract of sophora flower bud.
AB  - This study analysed the use of sophora flower bud extract for dyeing and the
      resulting colour character and fastness of dyed silk fabric. The pigment
      composition on the silk fabric and recycling of this extract were also studied.
      The results indicated that the dyed silk fabric possessed good washing, rubbing
      and perspiration fastness, and the pigment composition on the silk fabric was
      mainly rutin and quercetin. The average recovery rate of the dye was 55.00%.
      These results demonstrate that the sophora flower bud extract is an effective
      natural dye.

PMID- 28748728
TI  - Experiences and Attitudes Among Psychiatric Mental Health Advanced Practice
      Nurses in the Use of Telemental Health: Results of an Online Survey.
AB  - BACKGROUND: Telemental health (TMH) growth is driven by recent trends in health
      delivery systems and disparities in access to mental health services. There are
      currently no standard educational guidelines to prepare psychiatric mental health
      advanced practice nurses (PMH-APRNs) in TMH delivery. OBJECTIVE: To survey
      practicing PMH-APRNs across the United States about their experiences and
      attitudes about use of TMH. DESIGN: Eighty-three participants from the American
      Psychiatric Nurses Association online discussion board completed a nine-item
      survey. QUESTIONS INCLUDED: Length of time practicing as a PMH-APRN, TMH use in
      practice, populations served, and TMH background. RESULTS: A majority had been
      practicing as a PMH-APRN for less than a decade and had used TMH, although most
      reported no prior education or training in this delivery method. Participants did
      indicate a desire for TMH education. CONCLUSION: This survey affirms the
      prevalence of TMH use among PMH-APRN providers, lack of formal training, and
      necessity for standardized educational guidelines in TMH delivery.

PMID- 28748729
TI  - A Categorical Content Analysis of Highly Cited Literature Related to Trends and
      Issues in Special Education.
AB  - This investigation employs categorical content analysis processes as a mechanism
      to examine trends and issues in a sampling of highly cited (100+) literature in
      special education journals. The authors had two goals: (a) broadly identifying
      trends across publication type, content area, and methodology and (b)
      specifically identifying articles with disaggregated outcomes for students with
      learning disabilities (LD). Content analyses were conducted across highly cited
      (100+) articles published during a 20-year period (1992-2013) in a sample ( n =
      3) of journals focused primarily on LD, and in one broad, cross-categorical
      journal recognized for its impact in the field. Results indicated trends in the
      article type (i.e., commentary and position papers), content (i.e., reading and
      behavior), and methodology (i.e., small proportions of experimental and quasi
      experimental designs). Results also revealed stability in the proportion of
      intervention research studies when compared to previous analyses and a decline in
      the proportion of those that disaggregated data specifically for students with
      LD.

PMID- 28748730
TI  - Therapeutic targeting of leukemic stem cells in acute myeloid leukemia - the
      biological background for possible strategies.
AB  - INTRODUCTION: Acute myeloid leukemia (AML) is an aggressive malignancy, caused by
      the accumulation of immature leukemic blasts in blood and bone marrow. There is a
      relatively high risk of chemoresistant relapse even for the younger patients who
      can receive the most intensive antileukemic treatment. Treatment directed against
      the remaining leukemic and preleukemic stem cells will most likely reduce the
      risk of later relapse. Areas covered: Relevant publications were identified
      through literature searches. The authors searched for original articles and
      recent reviews describing (i) the characteristics of leukemic/preleukemic stem
      cells; (ii) the importance of the bone marrow stem cell niches in leukemogenesis;
      and (iii) possible therapeutic strategies to target the preleukemic/leukemic stem
      cells. Expert opinion: Leukemia relapse/progression seems to be derived from
      residual chemoresistant leukemic or preleukemic stem cells, and a more effective
      treatment directed against these cells will likely be important to improve
      survival both for patients receiving intensive treatment and leukemia-stabilizing
      therapy. Several possible strategies are now considered, including the targeting
      of the epigenetic regulation of gene expression, proapoptotic intracellular
      signaling, cell metabolism, telomere activity and the AML-supporting effects by
      neighboring stromal cells. Due to disease heterogeneity, the most effective stem
      cell-directed therapy will probably differ between individual patients.

PMID- 28748731
TI  - Long-term management of distinct facial flushing and persistent erythema of
      rosacea by treatment with carvedilol.
AB  - BACKGROUND: The treatment of persistent erythema and flushing episodes in
      patients with rosacea remains a clinical challenge. A possible therapeutic option
      could be the use of antihypertensive drugs. OBJECTIVES: We therefore evaluated
      the effect of the non-selective beta-blocker carvedilol in five Caucasian
      patients. METHODS: In a monocentric retrospective case study, the patients were
      treated with carvedilol titrated up to 12.5 mg twice a day over at least six
      months. Patients self assessment (PSA), clinicians erythema assessment (CEA), and
      the patients levels of embarrassment and satisfaction were performed by
      questionaires. RESULTS: The CEA grade description as well as the PSA grade
      description decreased remarkably in all five patients. Furthermore, all patients
      reported to have a major improvement of their level of satisfaction and no
      feelings of embarrassment anymore. CONCLUSIONS: These findings demonstrate that
      facial flushing and persistent erythema can be effectively treated by carvedilol
      long-term with a fast onset of improvement in a dose well tolerated.

PMID- 28748732
TI  - Split-root labelling to investigate 15N rhizodeposition by Pinus sylvestris and
      Picea abies.
AB  - We investigated the transfer of 15N into the soil via 15N uptake and release by
      tree roots, which involves the principles of the split-root technique. One half
      of the root system received an injection of (15NH4)2SO4 and the other half
      equivalent amounts of (NH4)2SO4 at 15N natural abundance level. 15N was
      transferred from one side of the root system (15N side) to the other side (14N
      side) and released into the soil. The method was conducted with Scots pine (Pinus
      sylvestris L.) and Norway spruce (Picea abies [L.] Karst). Two concentration
      levels of (NH4)2SO4 were used, corresponding with annual N deposition in the
      Netherlands (30 kg N ha-1) and a twelfth of that (2.5 kg N ha-1). Samples were
      taken 3 and 6 weeks after labelling and divided into needles + stem, roots,
      rhizosphere and bulk soil. Already 3 weeks after labelling, Scots pine took up
      23.7 % of the low and 9.1 % of the high amounts of 15N, while Norway spruce took
      up 21.5 and 32.1 %, respectively. Both species transported proportions of 15N to
      the rhizosphere (0.1-0.2 %) and bulk soil (0.3-0.9 %). The method is a useful
      tool to investigate the fate of root-derived N in soils, for example, for the
      formation of stable forms of soil organic matter.

PMID- 28748733
TI  - Sensory symptoms in low back pain-how do they matter?
AB  - OBJECTIVE: Successful treatment of chronic low back pain (LBP) is difficult in
      clinical practice and hard to measure in trials. One reason might be the use of
      insufficient outcome parameters. The aim was to investigate the importance of
      typical clinical characteristics of chronic LBP on QoL and functionality.
      METHODS: A total of 51 patients with chronic LBP (19 with, 32 without
      radiculopathy) were investigated with different questionnaires. RESULTS:
      Burdening symptoms differed in frequency, intensity and impairment of QoL and
      functionality between patients with and without radiculopathy and between the
      area of pain within the same patient, i.e. between back and leg. Symptoms of
      nerve affection such as prickling pain and numbness were rated higher in the area
      of radiating pain than on the back in radiculopathy, and typical neuropathic pain
      symptoms such as burning pain, prickling, spontaneous pain, and feeling of deep
      pressure and pain at the beginning of movement were rated with a higher
      impairment of QoL and functionality in patients with compared to those without
      radiculopathy. Furthermore, intensity, impairment of QoL, and functionality were
      not necessarily reported in association with one another: some patients were
      highly impaired in QoL or functionality, despite a moderate-to-low pain
      intensity, whereas others suffered from severe pain, but were less impaired in
      QoL or functionality. CONCLUSION: Results suggest the consideration of impairment
      of QoL and functionality in addition to symptom intensity for treatment
      evaluation of chronic LBP. This can help to improve overall well-being of the
      patients and enhance efficacy in clinical pain trials and patient-centered
      treatment.

PMID- 28748735
TI  - An EEG Investigation of the Attention-Related Impact of Mindfulness Training in
      Youth With ADHD: Outcomes and Methodological Considerations.
AB  - OBJECTIVE: The current study examined the impact of an activity-based mindfulness
      treatment on EEG indices of attention in youth with ADHD aged 11 to 17 years
      compared with a waitlist control group. METHOD: Pre- and post-treatment, EEG was
      recorded as participants completed a single-point focus rest task and two active
      attention tasks. Theta power, beta power, and theta/beta ratio (TBR) were
      calculated during each task. RESULTS: A significant group by time by task
      interaction was found that indicated significant improvement in attentional
      ability, indexed by decreased TBR, for the treatment group but not controls.
      CONCLUSION: Findings support the benefit of mindfulness treatment for enhancing
      attentional control in youth with ADHD and extend the literature by providing
      evidence of these gains at a neural level. Findings also offer methodological
      support for the use of active attention tasks when examining mindfulness-related
      attentional gains in youth with ADHD. Directions for future research are
      discussed.

PMID- 28748734
TI  - Biochemical alterations induced by nickel oxide nanoparticles in female Wistar
      albino rats after acute oral exposure.
AB  - CONTEXT: Nickel oxide (NiO) nanoparticles (NPs) with appropriate surface
      chemistry have been widely used for their potential new applications in
      biomedical industry. Increased usage of these NPs enhances the chance of exposure
      of personnel involved in the work place. OBJECTIVE: This study was designed to
      assess the ability of NiO NPs to cause biochemical alterations post-acute oral
      exposure in female Wistar rats. MATERIALS AND METHODS: Rats were administered
      with 125, 250, and 500 mg/kg doses of NiO NPs for haematological, biochemical,
      and histopathological studies. Biodistribution patterns of NiO NPs in female
      Wistar rats were also monitored. RESULTS: NiO NPs caused significant (p < 0.01)
      inhibition of RBC and brain AchE of treated rats at the high dose. Activation of
      the hepatotoxicity marker enzymes, aminotransferases, was recorded in serum and
      liver, whereas inhibition was observed in kidney. The activity of antioxidant
      enzymes was also altered by NiO NPs in a dose-dependent manner and found to be
      significant at the high dose of exposure. CONCLUSIONS: This study revealed that
      exposure to nanosized NiO particles at acute doses may cause adverse changes in
      animal biochemical profiles. Further, the in vivo studies on toxicity evaluation
      help in biomonitoring of the potential contaminants.

PMID- 28748736
TI  - Identification of bioactive constituents from different fractions of stems of
      Cuscuta reflexa Roxb. using GC-MS.
AB  - The GC-MS analysis of fractions of methanol extract of stem of Cuscuta reflexa
      (Family Convolvulaceae) was carried out using a THERMO TRACE 1300 Gas
      Chromatograph equipped and coupled to a mass detector THERMO TSQ 8000
      spectrometer with an TG 5MS (30 m * 0.25 mm, 0.25 MUm) of capillary column.
      Database of National Institute of Standards and Technology (NIST) library was
      used to identify the components. GC-MS revealed two known compounds i.e. 2
      Methoxy-4-vinyl phenol (6.80%) and Benzofuran-2,3-dihydro (20.89%) and other 12
      unknown compounds such as 3,5-di-tert-Butyl-4-hydroxyanisole (35.50%);
      Hexatriacontane (12.02%); n-Hexadecanoic acid (10.12%); Scoparone (7.97%);
      Hexadecanoic acid methyl ester (5.22%); 1,3-Benzenediamine, N, N, N', N'
      tetramethyl- (15.43%); Phenol, 4(3-hydroxy1propenyl), 2-methoxy (9.31%); Phenol,
      2,4 bis (1,1dimethylethyl); 2,3,5,6-Tetramethyl para phenylene diamine (14.18%);
      Retinoic acid-5,6-epoxy-5,6-dihydro (20.46%); 2,4-Dihydroxy-2,5-dimethyl
      3(2H)furan-3-one (10.13%); 2,3-dihydro-3,5-dihydroxy-6-methyl-2-Propyl-tetrahydro
      pyran-3-ol (10.13%); Pregn-4-ene-18-oic acid (5.75%) as some of the major
      compounds in its different fractions. Retinoic acid-5,6-epoxy-5,6-dihydro found
      as major compound may be responsible for blood glucose lowering potency.

PMID- 28748737
TI  - Emergency Hartmann's Procedure and Its Reversal: A Totally Laparoscopic 2-Step
      Surgery for the Treatment of Hinchey III and IV Diverticulitis.
AB  - BACKGROUND: Hartmann's procedure (HP) followed by reversal restoration is the
      first choice for treatment of diffuse diverticular peritonitis. There is no
      unanimous consensus regarding the use of laparoscopy to treat the same condition.
      METHODS: Data from 60 patients with diverticular diffuse peritonitis who
      underwent urgent HP followed by laparoscopic reversal were retrospectively
      analyzed. Patients were divided into 2 groups according to the open or
      laparoscopic HP (OHP, 24 patients; LHP, 36 patients). Outcomes were measured in
      terms of functional recovery, morbidity, mortality, and length of hospital stay.
      RESULTS: HPs showed no differences among the groups in terms of operative time,
      blood loss, and length of intensive care unit stay. Overall morbidity was
      significantly lower in LHP than in OHP, corresponding to 33.3% and 66.7%
      respectively ( P = .018). The incidence of both surgical and medical
      complications was higher in OHP than in LHP (41.7% vs 22.2% [ P = .044] and 45.8%
      vs 24.3% [ P = .023], respectively). Mortality was 16.6% for each group. LHP
      showed a faster return to bowel movements and a shorter hospital stay than OHP.
      The secondary intestinal reversal was possible in 92% of cases, successfully
      completed laparoscopically in 91.3%. No patients of LHP group required a
      conversion to open intestinal reversal. CONCLUSION: LHP for treatment of
      diverticular diffuse peritonitis showed significantly lower morbidity, faster
      recovery, shorter hospital stay, and higher rates of successful laparoscopic
      reversal when compared with OHP.

PMID- 28748738
TI  - Barriers and facilitators to healthy eating and disease self-management among
      older adults residing in subsidized housing.
AB  - BACKGROUND: As adults transition into older ages, meeting age-specific dietary
      recommendations can become increasingly challenging, especially for low-income
      seniors who reside in publicly subsidized rental housing. AIM: The primary
      objectives of this study were to: 1) identify barriers and facilitators to
      healthy eating and self-management of nutrition-related chronic illnesses
      experienced by low-income seniors residing in a subsidized housing setting; and
      2) assess the interest in community nutrition programming among low-income
      seniors residing in a subsidized housing setting. METHOD: A qualitative study
      design, using food focus groups and food pantry observations, was used.
      Participants included 24 male and female senior adults, between 65 and 75 years
      of age, residing in a subsidized housing community in Philadelphia, PA. This
      setting also included the unique features of a community garden and food pantry.
      Data were manually analyzed using a content analysis approach, which included
      familiarization, identification of themes, categorization and interpretation; and
      verified using NVivo 10. RESULTS: Personal barriers, including food cost and
      accessibility, physical limitations, desire for convenience, and low self
      efficacy to change dietary habits, inhibited motivation to change. External
      barriers in the food environment, including lack of transportation and distance
      of markets to access fresh produce, were commonly cited; as well as negative
      influences of the internal environment, such as the presence of vending machines,
      common cultural cooking and eating practices, and the lack of social cohesion.
      Facilitators focused on food preparation and recipe adaptation. CONCLUSIONS:
      Participants expressed an interest in learning more about food, nutrition, and
      health through community-based programming.

PMID- 28748739
TI  - Multiplex PCR assay discriminates rabbit, rat and squirrel meat in food chain.
AB  - Rabbit meat is receiving increasing attention because it contains a high level of
      proteins with relatively little fat. On the other hand, squirrel meat is served
      in upper-class meals in certain countries, so is sold at higher prices. The other
      side of the coin is rat meat, which has family ties with rabbit and squirrel but
      poses substantial threats to public health because it is a potential carrier of
      several zoonotic organisms. Recently, rat meat was mislabelled and sold as lamb
      after chemical modification. Thus, the chances of rabbit and squirrel meat
      substitution by rat meat cannot be ruled out. For the first time, a multiplex PCR
      assay was developed in Malaysia for the discriminatory identification of rat,
      rabbit and squirrel in the food chain. Rabbit (123 bp), rat (108 bp) and squirrel
      (243 bp) targets were amplified from ATP6 and cytb genes, along with a eukaryotic
      internal control (141bp). The products were sequenced and cross-tested against 22
      species. A total of 81 reference samples and 72 meatball specimens were screened
      to validate the assay. Analyte stability was evaluated through boiling,
      autoclaving and micro-oven cooking. The tested lower limits of detection were
      0.01 ng DNA for pure meat and 0.1% for meatballs.

PMID- 28748740
TI  - The use of fluoroscopic guided percutaneous pedicle screws in the upper thoracic
      spine (T1-T6): Is it safe?
AB  - PURPOSE: This study analysed the accuracy and safety of the fluoroscopic guided
      percutaneous screws in the upper thoracic vertebrae (T1-T6). METHODS: Computed
      tomography scans from 74 patients were retrospectively evaluated between January
      2008 and December 2012. Pedicle perforations were classified by two types of
      grading systems. For medial, lateral, superior and inferior perforations: grade 0
      - no violation; grade 1 - <2 mm; grade 2 - 2-4 mm and grade 3 - >4 mm. For
      anterior perforations: grade 0 - no violation; grade 1 - <4 mm; grade 2 - 4-6 mm
      and grade 3 - >6 mm. RESULTS: There were 35 (47.3%) male and 39 (52.7%) female
      patients with a total 260 thoracic pedicle screws (T1-T6) analysed. There were 32
      screw perforations which account to a perforation rate of 12.3% (11.2% grade 1,
      0.7% grade 2 and 0.4% grade 3). None led to pedicle screw-related complications.
      The perforation rate was highest at T1 (33.3%, all grade 1 perforations),
      followed by T6 (14.5%) and T4 (14.0%). CONCLUSION: Fluoroscopic guided
      percutaneous pedicle screws of the upper thoracic spine (T1-T6) are technically
      more demanding and carry potential risks of serious complications. Extra
      precautions need to be taken when fluoroscopic guided percutaneous pedicle screws
      are placed at T1 and T2 levels, due to high medial pedicular angulation and
      obstruction of lateral fluoroscopic images by the shoulder girdle and at T4-T6
      levels, due to smaller pedicular width.

PMID- 28748741
TI  - Nursing Student Attitudes toward Euthanasia: A Cross-Sectional Study.
AB  - BACKGROUND: Euthanasia is among the most common and controversial end-of-life
      care issues. Examining the attitudes of nursing students to this issue is
      important because they may well encounter these issues during the course of their
      clinical placements. Research aims: This study aims to examine the attitudes of a
      sample of Iranian nursing students towards euthanasia. RESEARCH DESIGN: This is a
      descriptive cross-sectional study. Participants and research context: Using
      convenience sampling, 382 Muslim nursing students were enrolled in this study.
      METHODS: Data were collected using a demographic variables checklist and a self
      administered questionnaire that included a definition of euthanasia and 11 closed
      questions that sought to record participants' level of agreement with euthanasia
      based on a Likert scale. Ethical consideration: Consent for participation was
      implicit, indicated by the participants having returned the completed
      questionnaires. Participants were assured that their data would remain anonymous,
      be kept confidential and be stored safely. FINDINGS: Of the 382 participants,
      61.5% were female, and the remainder were male. The mean age was 62.6 +/- 14.1
      years (range: 32-91 years). In total, 34.2%, 41.6% and 24% of students reported a
      negative, neutral and positive attitude to euthanasia, respectively. Most
      students with clinical experience, and 38.5% of students with no clinical
      experience, indicated their agreement with active euthanasia. DISCUSSION: There
      are a number of misconceptions among Iranian Muslim nursing students regarding
      the definition of euthanasia. Nonetheless, most students exhibit positive
      attitudes to euthanasia consistent with their clinical experiences. CONCLUSION:
      It is recommended to explore the factors that induced nursing students' tendency
      to euthanasia.

PMID- 28748742
TI  - Formation of magnesium hydrosilicate nanomaterials and its applications for
      phosphate/ammonium removal.
AB  - Nanomaterials of magnesium hydrosilicate Mg3Si2O5(OH)4 were developed for
      phosphate and ammonium recovery from wastewater in virgin, which had the
      structure of diffuse interlamellar order, and synthesized under hydrothermal
      conditions at temperatures of 200 degrees C for 36-72 h from mixtures of
      magnesite and zeolite as mineralizers. The amount of magnesium released has gone
      up to 48 mg/g by magnesium hydrosilicate, which was increased with the increase
      in the weight ratio of magnesite:zeolite. When magnesium hydrosilicate was used
      to adsorb phosphate and ammonium, electrostatic adsorption was not a dominant
      mechanism, the adsorbing capacity of phosphate was about 19 mg/g, and the
      simultaneous adsorbing capacity of ammonium was 7.8 mg/g.

PMID- 28748743
TI  - Community-based game intervention to improve South Asian Indian Americans'
      engagement with advanced care planning.
AB  - OBJECTIVE: Advance care planning (ACP) allows individuals to express their
      preferences for medical treatment in the event that they become incapable of
      making their own decisions. This study assessed the efficacy of a conversation
      game intervention for increasing South Asian Indian Americans' (SAIAs')
      engagement in ACP behaviors as well as the game's acceptability and cultural
      appropriateness among SAIAs. DESIGN: Eligible community-dwelling SAIAs were
      recruited at SAIA cultural events held in central Texas during the summer of
      2016. Pregame questionnaires included demographics and the 55-item ACP Engagement
      Survey. Played in groups of 3-5, the game consists of 17 open-ended questions
      that prompt discussions of end-of-life issues. After each game session, focus
      groups and questionnaires were used to examine the game's cultural
      appropriateness and self-rated conversation quality. Postintervention responses
      on the ACP Engagement Survey and rates of participation in ACP behaviors were
      collected after 3 months through phone interviews or online surveys. Data were
      analyzed using descriptive statistics, frequencies, and paired t-tests comparing
      pre/post averages at a .05 significance level. RESULTS: Of the 47 participants,
      64% were female, 62% had graduate degrees, 92% had lived in the U.S. for >10
      years, 87% were first-generation immigrants, and 74% had no advance directive
      prior to the game. At the 3-month follow-up, 58% of participants had completed at
      least one ACP behavior, 42% had discussed end-of-life issues with loved ones, 15%
      did so with their healthcare providers, and 18% had created an advanced
      directive. ACP Engagement Survey scores increased significantly on all four of
      the process subscales by 3 months postgame. CONCLUSION: SAIA individuals who
      played a conversation game had a relatively high rate of performing ACP behaviors
      3 months after the intervention. These findings suggest that conversation games
      may be useful tools for motivating people from minority communities to engage in
      ACP behaviors.

PMID- 28748744
TI  - Prevalence, Incidence, and Persistence of Postpartum Depression, Anxiety, and
      Comorbidity among Chinese Immigrant and Nonimmigrant Women: A Longitudinal Cohort
      Study.
AB  - OBJECTIVE: Our objectives were to examine the prevalence and incidence of
      postpartum depressive, anxiety, and comorbid symptoms over the first postpartum
      year; the persistence of these symptoms; and the prevalence stratified by
      immigration status. METHOD: We conducted a longitudinal cohort study in Ontario,
      Canada. Participants were 571 Chinese recent immigrant, nonrecent immigrant, and
      Canadian-born women with live births in 2011 to 2014. Participants were assessed
      at 4, 12, and 52 weeks postpartum for the presence of possible and high
      depressive symptomatology (Edinburgh Postnatal Depression Scale [EPDS] >9 and
      >12, respectively), anxiety symptomatology (State-Trait Anxiety Inventory [STAI]
      >40), and comorbid symptomatology (EPDS >9 and STAI >40). Prevalence and
      incidence with 95% confidence intervals were calculated. RESULTS: Prevalence
      rates were highest at 4 weeks and decreased across time, with possible depressive
      symptomatology most prevalent at most time points. Incidence rates at 12 and 52
      weeks were generally similar. Of those with possible symptomatology at 4 weeks,
      42.0% or less continued to have symptomatology at 12 weeks and 17.4% or less at
      52 weeks. There were no differences in prevalence of any type of symptomatology
      between immigrant and Canadian-born Chinese women at 4 weeks, but at 12 and 52
      weeks, most types of symptomatology were more common among recent and nonrecent
      immigrants. CONCLUSION: Our findings suggest that Chinese immigrant women are a
      high-risk group for postpartum depressive and anxiety symptomatology. Future
      research should identify cultural and psychosocial factors associated with
      immigration that could be addressed in the system of care for postpartum
      immigrant women.

PMID- 28748745
TI  - Histamine poisoning from insect consumption: an outbreak investigation from
      Thailand.
AB  - BACKGROUND: Insect consumption is a common practice in the Asian culture and all
      over the world. We are reporting an outbreak investigation of histamine poisoning
      from ingestion of fried insects. METHODS: On 24 July 2014, a group of students at
      a seminar presented to Angthong Provincial Hospital, Thailand, with pruritic rash
      after ingesting snacks consisting of fried insects from a vendor. We initiated an
      outbreak investigation with retrospective cohort design and collected samples of
      remaining foods for analyses. Attack rates, relative risks and their confidence
      intervals (CI) were calculated. RESULTS: Out of 227 students, 28 developed
      illnesses that were consistent with our case definition which included, flushing,
      pruritus, urticarial rashes, headache, nausea, vomiting, diarrhea, dyspnea and
      bronchospasm. Two children were hospitalized for progressive bronchospasm
      overnight without serious complications. The types of food ingested included a
      lunch that was provided at the seminar for all students and snacks that 41
      students bought from the only vendor in the vicinity. The snacks included fried
      grasshoppers, silkworm pupae, common green frogs, bamboo borers, crickets and
      meat balls. The attack rates were highest (82.6 and 85.0%) among students who
      ingested fried grasshoppers and silkworm pupae and lowest (4.4 and 5.3%) among
      those who did not ingest them, with relative risk of 18.7 (95% CI 9.6-36.4) for
      grasshoppers and 16.0 (95% CI 8.8-29.3) for silkworm pupae. Histamine
      concentrations in the fried grasshoppers and silkworm pupae were 9.73 and 7.66
      mg/100g, respectively. DISCUSSION AND CONCLUSION: Through epidemiological
      analysis and laboratory confirmation, we have illustrated that histamine
      poisoning can occur from ingestion of fried insects. We postulate that histidine,
      which is present in high concentration in grasshoppers and silkworm pupae, is
      decarboxylated by bacteria to histamine, a heat stable toxin. The ingestion of
      histamine is responsible for the clinical pictures being reported.

PMID- 28748746
TI  - Long-term urodynamic findings following radical prostatectomy and salvage
      radiotherapy.
AB  - OBJECTIVE: Lower urinary tract symptoms (LUTS) are common following radical
      prostatectomy (RP) or intended curative radiotherapy in prostate cancer patients.
      One-quarter of those treated with RP experience biochemical failure and are
      subsequently offered salvage radiotherapy (SRT) to the prostatic bed. The aim of
      this study was to elucidate long-term LUTS after surgery and SRT. MATERIALS AND
      METHODS: Urodynamic parameters from 16 patients treated with RP and subsequent
      SRT in the period 2000-2010 were evaluated with uroflowmetry, filling cystometry,
      pressure-flow and urethral pressure profile (UPP). In conjunction with the
      urodynamic examination, all patients completed the Danish Prostatic Symptom Score
      (DAN-PSS) questionnaire, which evaluates the grade of LUTS. RESULTS: Median time
      from SRT to urodynamic examination was 7.7 years (range 5.8-10.0 years). The
      following urodynamic parameters were affected: bladder volume at maximal
      cystometric capacity, bladder compliance, bladder function, bladder outlet
      obstruction and UPP. The total DAN-PSS index combining all symptoms and their
      corresponding impact on patients was mild in six patients (<= 7 points), moderate
      in seven patients (8-19 points) and severe in three patients (>= 20 points).
      CONCLUSIONS: This urodynamic study is one of the first to evaluate long-term
      urodynamic characteristics in patients treated with SRT. Several urodynamic
      parameters were affected. This indicates that SRT primarily affects bladder
      compliance, maximal cystometric capacity and bladder outlet obstruction. LUTS
      were proven to be strongly related to urodynamic parameters.

PMID- 28748747
TI  - Association between metabolic syndrome and overactive bladder: a case-control
      study.
AB  - OBJECTIVE: The aim of this case-control study was to investigate the association
      between overactive bladder (OAB) and metabolic syndrome (MetS). The primary
      hypothesis was that OAB is significantly more prevalent among patients with MetS
      than in control participants. MATERIALS AND METHODS: A case-control study was
      conducted among 114 patients, with 57 patients in the MetS group and 57 in the
      control group. Study participants were recruited in a family medicine practice.
      They filled out a questionnaire including questions on age, gender, clinical
      symptoms, lifestyle and coping behaviors, and the Overactive Bladder Validated 8
      question Awareness Tool (OAB-V8) questionnaire. RESULTS: In the MetS group, 74%
      (n = 42) of patients screened positive on the OAB-V8 questionnaire (score >=8),
      which was significantly higher than 29% (n = 17) of patients in the control group
      (p < 0.001). Lifestyle and coping behaviors associated with OAB were more
      prevalent in the MetS group. Screening positive on the OAB screening tool was
      associated with having MetS (p < 0.001), older age (p = 0.004), higher prevalence
      of using a diuretic (p = 0.002), avoiding places if they think there will not be
      a restroom (toilet) nearby (p = 0.015), going to the restroom so often that it
      interferes with things they want to do (p = 0.046) and bladder symptoms making
      them feel like there is something wrong with them (p < 0.001). CONCLUSIONS: OAB
      is significantly more prevalent in patients suffering from MetS than in those
      without MetS. Assessment of the presence and monitoring of OAB should be part of
      the clinical management of patients with MetS.

PMID- 28748748
TI  - Outcome study of the pipeline embolization device for treatment of intracranial
      aneurysms at a single UK institution.
AB  - BACKGROUND: The introduction of flow-diverting stents in the last decade provides
      an alternative endovascular treatment choice in selected intracranial aneurysms.
      This retrospective analysis of a UK centre's experience provides insight into
      clinical and radiographic outcomes. METHODS: Electronic patient records,
      diagnostic and procedural images and written procedural records for patients
      treated with the PED between August 2009 and April 2014 were reviewed. Follow-up
      TOF MRA was performed after treatment. Clinical and radiographic outcomes were
      analyzed and compared with other PED studies. RESULTS: Twenty-nine patients with
      30 attempted PED treatments were reviewed representing 3.5% of the treated
      aneurysm patient cohort. 63.6% (21/33) of the aneurysms were wide-necked (>4 mm),
      60.6% (20/33) were large or giant (>=10 mm). The mean aneurysm sac diameter was
      12.0 mm; the mean neck width was 4.5 mm. Mortality and morbidity rates were 3.3%
      and 10.0%, respectively. The total adequate occlusion rate was 78.1% (25/32) at
      18 months. The neck width of aneurysms with residual sac filling and complete
      occlusion differed significantly (p = 0.04). CONCLUSIONS: Highly selected
      aneurysms treated with a PED in a UK centre have similar occlusion and
      complication rates when compared to non-UK studies. Again, it appeared that
      delayed aneurysm rupture remained a risk for PED treatment in large or giant
      aneurysms. Follow-up with TOF MRA gave similar occlusion results compared to
      those obtained with DSA in other studies. The influence of neck size on occlusion
      rate should be examined in future PED studies.

PMID- 28748749
TI  - Spyridon Magginas (1839-1920) and One of the First Successful Radical
      Nephrectomies.
AB  - Spyridon Magginas was among the Greek doctors of the turn of the century who
      trained abroad with the hope of returning to their native country to offer their
      services. He became a professor in the "Othonion University" of Athens to promote
      surgery among young physicians. He was raised in an upper social class family
      and, reportedly, had an arrogant behaviour, which occasionally led him to have
      ineffective patient interactions. His patient, and an important Greek writer,
      Emmanuel Rhoides, nicknamed him the "surgeon beast" for neglecting his case.
      However, Magginas was an innovative surgeon and in 1902, completed the first
      successful radical nephrectomy in Greece, and possibly one of the first few
      globally of the 20th century. A key factor in his success was the prioritisation
      and application of strict antisepsis.

PMID- 28748751
TI  - Update on Nitazoxanide: A Multifunctional Chemotherapeutic Agent.
AB  - BACKGROUND: The thiazolide nitazoxanide (NTZ) is a broad-spectrum antiinfective
      drug that adversely affects viability, growth, and proliferation of a range of
      extracellular and intracellular protozoan, helminths, anaerobic and
      microaerophilic bacteria, and viruses. METHOD: Current review compiled the
      potential chemotherapeutic efficacy of NTZ against a variety of such disease
      causing macro and/or micro-organisms as well as neoplastic cells, using various
      search engines viz. Web of Science, Scopus and Pub- Med up to February 2017.
      RESULT: The most accepted anti-infective mechanism of NTZ involves impairment of
      the energy metabolism in anaerobic pathogens by inhibition of the pyruvate:
      ferredoxin/ flavodoxin oxidoreductase (PFOR). In parasitic-protozoan NTZ also
      induces lesions/voids in the cell membrane and depolarises the mitochondrial
      membrane along with the inhibition of quinone oxidoreductase NQO1, nitroreductase
      1 and protein disulphide isomerase. NTZ also inhibits the glutathione-S
      transferase (a major detoxifying enzyme) and modulates a gene (avr-14 gene)
      encoding for the alphatype subunit of glutamate-gated chloride ion channel
      present in the nematodes. Apart from well recognized non-competitive inhibition
      of the PFOR in anaerobic bacteria, NTZ also showed a variety of other
      antibacterial mechanisms viz. inhibits pyruvate dehydrogenase in the Escherichia
      coli, disrupts the membrane potential and pH homeostasis in the Mycobacterium
      tuberculosis, suppresses the chaperone/usher (CU) pathway of the gram-negative
      bacteria and stimulates host macrophage autophagy in the tubercular patients. NTZ
      also suppresses the viral replication by inhibiting maturation of the viral
      hemagglutinin and the viral transcription factor immediate early 2 (IE2) as well
      as by activating the eukaryotic translation initiation factor 2alpha (an
      antiviral intracellular protein). Additionally, NTZ expresses inhibitory effect
      on the tumour cell progression by modulating drug detoxification (glutathione-S
      transferase P1), unfolded protein response, autophagy, anti-cytokines activities
      and c-Myc inhibition. CONCLUSION: These potentially versatile molecular
      interactions of NTZ within invading pathogen(s) and immunomodulatory efficacy
      over the hosts, justify the multifunctional chemotherapeutic significance of this
      chemical agent.

PMID- 28748750
TI  - Chemical Space of FLT3 Inhibitors as Potential Anti-AML Drugs.
AB  - BACKGROUND: FLT3 is a member of receptor tyrosine kinase III family, mainly
      expressed in hematopoietic cells. The aberrant expression and function of FLT3
      are strongly related to leukemia, especially acute myeloid leukemia. Its
      varieties of amino-acid residues mutations, such as FLT3-ITDs and -TKDs, can
      induce constant proliferation of hematological tumor cells with poor prognosis.
      Hence FLT3 serves as a promising target in AML chemotherapy. OBJECTIVE: This
      review focused on the progress of FLT3 inhibitors study including those that have
      entered clinical trials or were reported in numerous patents all over the world.
      Thus, we provided a useful reference for the development of new anti-leukemia
      drugs. METHOD: Through a comprehensive retrospective study, FLT3 inhibitors in
      several patent applications were identified and classified into five categories,
      including quinolone-related, indole-related, ureas, pyrimidines and other
      compounds. RESULTS: For each category of compounds, the structural feature, SAR,
      biological activity and current research status were thoroughly reviewed and
      analyzed. CONCLUSION: Although some of those compounds expressed potent
      bioactivities and have reached the advanced clinical trials for the treatment of
      leukemia, there are still several problems need to be faced before they enter the
      market eventually, especially the drug resistance issue. The improvement of
      therapeutic potency for FLT3 inhibitors might depend on the useful combination
      therapy and further refinement of the intrinsic properties of FLT3 inhibitors.

PMID- 28748752
TI  - Commentary: Toward a Personalized Medicine in Wake-Up Stroke?

PMID- 28748753
TI  - Investigating the Practices of Patients and Hospitals in Treatment of Diabetes -
      A Survey Questionnaire for Arabic Speaking Countries.
AB  - BACKGROUND: Diabetes is one of the most chronic diseases prevalent in Kingdom of
      Saudi Arabia. Its number of patients have increased in past few decades. Best
      efforts to provide world class treatments to patients through public and private
      hospitals are in hand. However, feedback of practices observed by patients and
      hospitals is not being achieved to assess the treatment efficacy. Absence of an
      elaborated questionnaire in Arabic language is a major hurdle to seek information
      from patients' due to their limited knowledge of English language in which most
      of the survey questionnaire exist in internationally published literature.
      CONCLUSION: In present research one such questionnaire was adapted and translated
      into Arabic language for survey of patients in a local hospital. A total of 191
      patients participated in this investigation. Results of findings are analyzed on
      the basis of demographics, diagnostics, tests and various aspects of diabetes
      self-management by patients.

PMID- 28748754
TI  - Neuroprotection in Hypoxic-Ischemic Brain Injury Targeting Glial Cells.
AB  - Brain injury constitutes a disabling health condition of several etiologies. One
      of the major causes of brain injury is hypoxia-ischemia. Until recently,
      pharmacological treatments were solely focused on neurons. In the last decades,
      glial cells started to be considered as alternative targets for neuroprotection.
      Novel treatments for hypoxia-ischemia intend to modulate reactive forms of glial
      cells, and/or potentiate their recovery response. In this review, we summarize
      these neuroprotective strategies in hypoxia-ischemia and discuss their mechanisms
      of action.

PMID- 28748755
TI  - Biotin and Glutathione Targeting of Solid Nanoparticles to Cross Human Brain
      Endothelial Cells.
AB  - BACKGROUND: The blood-brain barrier restricts drug penetration to the central
      nervous system. Targeted nanocarriers are new potential tools to increase the
      brain entry of drugs. Ligands of endogenous transporters of the blood-brain
      barrier can be used as targeting vectors for brain delivery of nanoparticles.
      OBJECTIVE: We tested biotin-labeled solid nanoparticles for the first time and
      compared to biotinylated glutathione- labeled nanoparticles in brain endothelial
      cells. METHOD: Neutravidin coated fluorescent polystyrene nanoparticles were
      derivatized with biotin and biotinylated glutathione. As a human in vitro blood
      brain barrier model hCMEC/D3 brain endothelial cells were used. Cell viability by
      MTT test, uptake and transfer of the nanoparticles across the endothelial
      monolayers were measured. The uptake of the nanoparticles was visualized by
      confocal microscopy. RESULTS: The tested nanoparticles caused no change in cell
      viability. The uptake of biotin- and glutathione-labeled nanoparticles by brain
      endothelial cells was time-dependent and significantly higher compared to non
      labeled nanoparticles. The penetration of the glutathione-labeled nanoparticles
      across the endothelial monolayer was higher than the biotin-targeted ones. Biotin
      and glutathione-targeted nanoparticles were visualized in hCMEC/D3 cells. We
      verified that hCMEC/D3 express mRNA for sodium-dependent multivitamin transporter
      (SMVT/SLC5A6) responsible for the blood-brain barrier transport of biotin.
      CONCLUSION: Biotin as a ligand increased the uptake and the transfer of
      nanoparticles across brain endothelial cells. Biotinylated glutathione could
      further increase nanoparticle permeability through endothelial monolayers
      supporting its use as a brain targeting vector.

PMID- 28748756
TI  - Activity of Saponins from Medicago species Against HeLa and MCF-7 Cell Lines and
      their Capacity to Potentiate Cisplatin Effect.
AB  - BACKGROUND: Saponins from Medicago species display several biological activities,
      among them apoptotic effects against plant cells have been evidenced. In
      contrast, their cytotoxic and antitumor activity against animal cells have not
      been studied in great details. OBJECTIVE: To explore the cytotoxic properties of
      saponin from Medicago species against animal cells and their effect in
      combination with the antitumoral drug cisplatin. METHOD: Cytotoxic activity of
      saponin mixtures from M. arabica (tops and roots), M. arborea (tops) and M.
      sativa (tops, roots and seeds) and related prosapogenins from M. arborea and M.
      sativa (tops) against HeLa and MCF-7 cell lines is described. In addition,
      cytotoxicity of soyasaponin I and purified saponins (1-8) of hederagenin,
      medicagenic and zanhic acid is also presented. Combination experiments with
      cisplatin have been also conducted. RESULTS: Saponins from M. arabica tops and
      roots (mainly monodesmosides of hederagenin and bayogenin) were the most
      effective to reduce proliferation of HeLa and MCF-7 cell lines. Among the
      purified saponins, the most cytotoxic was saponin 1, 3-O-beta-D-glucopyranosyl(1
      >2)-alpha-L-arabinopyranosyl hederagenin. When saponins, derived prosapogenins
      and pure saponins were used in combination with cisplatin, they all, to different
      extent, were able to potentiate cisplatin activity against HeLa cells but not
      against MCF-7 cell lines. Moreover uptake of cisplatin in these cell lines was
      significantly reduced. CONCLUSION: Overall results showed that specific molecular
      types of saponins (hederagenin glycosides) have potential as anti-cancer agents
      or as leads for anti-cancer agents. Moreover saponins from Medicago species have
      evidenced interesting properties to mediate cisplatin effects in tumor cell
      lines.

PMID- 28748757
TI  - Potential triazole-based molecules for the treatment of neglected diseases.
AB  - Neglected Diseases (NDs) affect million of people, especially the poorest
      population around the world. Several efforts to an effective treatment have
      proved insufficient at the moment. In this context, triazole derivatives have
      shown great relevance in medicinal chemistry due to a wide range of biological
      activities. This review aims to describe some of the most relevant and recent
      research focused on 1,2,3- and 1,2,4-triazole-based molecules targeting four
      expressive NDs: Chagas disease, Malaria, Tuberculosis and Leishmaniasis.

PMID- 28748758
TI  - Protozoan parasites glycosylphosphatidylinositol anchors: structures, functions
      and trends for drug discovery.
AB  - Glycosylphosphatidylinositol (GPI) anchors are complex molecules that support
      certain proteins in the outer leaflet of the cell membrane. The GPI anchor
      scaffold is comprised of a glycan core which contains a phosphoethanolamine
      linker and a phospholipid chain. GPI-anchored proteins are structurally and
      functionally diverse and play essential roles in several biological processes, in
      particular cell-cell interaction. Although all eukaryotes possess GPI anchors in
      their cell membrane, protozoan parasites use this anchorage much more frequently
      than higher eukaryotes. There is extensive evidence that parasites&#039; GPI
      anchors are important for virulence and interaction with host cells, as well as
      their own survival and viability. Structural and biosynthetic pathway differences
      between many parasites and mammalian cells have been explored for further
      understanding about functions and importance of these molecules. Some GPI
      biosynthesis enzymes have been proposed as alternative targets for therapy
      against parasitic diseases. This review discusses concisely the main differences
      between parasitic and mammalian GPI anchor biosynthesis, and highlights the
      implications of structural variation. Moreover, advances in drug discovery based
      on GPI anchor structures and biosynthetic pathway are outlined.

PMID- 28748759
TI  - Targeting Kinase-activating Genetic Lesions to Improve Therapy of Pediatric Acute
      Lymphoblastic Leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in
      children, characterized by an abnormal proliferation of immature lymphoid cells.
      Thanks to risk-adapted combination chemotherapy treatments currently used,
      survival at 5 years has reached 90%. ALL is a heterogeneous disease from a
      genetic point of view: patients' lymphoblasts may harbor in fact several
      chromosomal alterations, some of which have prognostic and therapeutic value. Of
      particular importance is the translocation t(9;22)(q34;q11.2) that leads to the
      formation of the BCR-ABL1 fusion gene, encoding a constitutively active chimeric
      tyrosine kinase (TK): BCR-ABL1 that is present in ~3% of pediatric ALL patients
      with B-immunophenotype and is associated with a poor outcome. This type of ALL is
      potentially treatable with specific TK inhibitors, such as imatinib. Recent
      studies have demonstrated the existence of a subset of BCR-ABL1 like leukemias
      (~10-15% of Bimmunophenotype ALL), whose blast cells have a gene expression
      profile similar to that of BCR-ABL1 despite the absence of t(9;22)(q34;q11.2).
      The precise pathogenesis of BCR-ABL1 like ALL is still to be defined, but they
      are mainly characterized by the activation of constitutive signal transduction
      pathways due to chimeric TKs different from BCR-ABL1. BCR-ABL1 like ALL patients
      represent a group with unfavorable outcome and are not identified by current risk
      criteria. In this review, we will discuss the design of targeted therapy for
      patients with BCR-ABL1 like ALL, which could consider TK inhibitors, and discuss
      innovative approaches suitable to identify the presence of patient's specific
      chimeric TK fusion genes, such as targeted locus amplification or proteomic
      biosensors.

PMID- 28748760
TI  - Visible Light Therapy: Molecular Mechanisms and Therapeutic Opportunities.
AB  - Visible light is absorbed by photoacceptors in pigmented and non-pigmented
      mammalian cells, activating signaling cascades and downstream mechanisms that
      lead to the modulation of cellular processes. Most studies have investigated the
      molecular mechanisms and therapeutic applications of UV and the red to near
      infrared regions of the visible spectrum. However, considerably less effort has
      been dedicated to the UV-free blue part of the spectrum. In this review we
      discuss the current advances in the understanding of the molecular
      photoacceptors, downstream signaling mechanisms and the corresponding therapeutic
      opportunities in the context of inflammatory skin conditions of blue light
      photoreception in mammalian cells. At a molecular level, blue light is absorbed
      by flavins, porphyrins, nitrosated proteins and opsins, and induces the release
      of reactive oxygen species, nitric oxide, and activation of G protein coupled
      signaling, respectively. Limited and contrasting results have been reported on
      the downstream cellular effects of blue light induced signaling. Some
      investigations describe a regulation of cellular proliferation and
      differentiation or a modulation of inflammatory parameters while others show
      growth inhibition and apoptosis. Regardless of the elusive underlying mechanism,
      blue light has been shown to be beneficial in treating inflammatory skin
      conditions, which are characterized by sustained inflammation and
      hyperproliferation of skin cells. However, to strengthen the use of UV-free blue
      light for therapeutic applications, further in depth studies of the underlying
      molecular and cellular mechanisms and their translation into clinical
      applications are clearly needed.

PMID- 28748761
TI  - Tyrosinase Electrochemical Biosensors Monitoring Medicinally Significant
      Substances.
AB  - Nowadays in biosensing, development of analytical techniques is focused on
      improvement for monitoring biologically active species in living organisms,
      especially in real-time analysis. This article provides an overview of
      applications of electrochemical tyrosinase biosensors in the analysis of
      medicinally significant substances, also known as biomarkers. At the beginning,
      special attention is paid to characterisation of the tyrosinase enzyme,
      explanation of reaction mechanisms of tyrosinase with various types of
      electrochemical transducers and techniques needed for stable immobilization of
      this biocatalyst on the transducer surface used. In this case, amperometric
      transducers represent the most frequently used type of electrochemical sensing
      because they usually provide sensitive current response to the presence of
      analyte in the sample. Many scientific works suggest that these very selective
      bioanalytical devices could find application in the clinical diagnosis of various
      serious diseases because they represent the effective analytical tools for
      diagnosis of neurodegenerative disorders, detection of microbial pathogens
      responsible for foodborne illness and diagnosis of cytopathology, especially
      melanoma cancer. Additionally, various kinds of electrochemical tyrosinase
      biosensors are presented which were developed to determine the catalytic activity
      of other enzymes significant for human metabolism, medicaments and their
      metabolic products, several hormones, amino acids and proteins. Despite all of
      their advantages, it is necessary to state that tyrosinase biosensors are still
      not used in the routine laboratory practice due to their relatively short service
      life which is not longer than one month unfortunately. Never-ending development
      of catalytic polymers imitating the tyrosinase active site could be one of ways
      to solve this serious drawback.

PMID- 28748762
TI  - Post cardiovascular surgery atrial fibrillation. Biomarkers determining
      prognosis.
AB  - New onset of atrial fibrillation (AF) after cardiovascular surgery is associated
      with increased risk of complications and length of hospital stay. Identification
      of patients at high risk of post cardiovascular surgery AF may help to act with
      preventive strategies having clinical and economic relevance. Many factors such
      as cardiac remodelling, changes in atrial pressure, surgery trauma, inflammation,
      oxidative stress, and sympathetic/parasympathetic activation have been implicated
      in the development of post cardiovascular surgery. On the basis of multifactorial
      mechanism underlining the onset of post cardiac surgery AF, several studies had
      investigated the predictive role of some serum biomarkers. The focus of this
      review is to summarize findings on biomarkers of myocardial fibrosis (PICP and
      PIIINP), profibrotic mediators (TGF-beta1), extracellular matrix remodeling (MMP
      9), myocardial stretch (BNP and NTpro-BNP), inflammation (interleukins, c
      reactive protein and sCD40L), and myocardial necrosis (high-sensitivity troponin
      T), for being used in clinical practice to stratify patient' risk of post
      cardiovascular surgery AF.

PMID- 28748763
TI  - Induced Pluripotent Stem Cell Technology: A Paradigm Shift in Medical Science for
      Drug Screening and Disease Modeling.
AB  - BACKGROUND: Induced Pluripotent Stem Cell (IPSC) Technology is the most advanced
      research as it offers an attractive alternative for establishing patient-specific
      IPSCs to recapitulate phenotypes of not only monogenic diseases (viz.
      Thalassaemia, Sickle cell anemia, Haemophilia, Tay-Sachs disease), but also late
      onset polygenic diseases (viz. Parkinson's disease, Alzheimer's disease,
      schizophrenia). Over the hindsight, numerous studies of the past and current
      scientists have led to the production, maturation and understanding of induced
      pluripotent stem cell technology and its use in basic and clinical research.
      METHODS: A systematic search of peer-reviewed scientific literature and clinical
      trials in public databases were carried out to summarize the evidence on the use
      of IPSC. RESULTS: Current review sheds light upon the use of patient-derived iPSC
      models in drug toxicity, screening and discovery which have been derived after
      referring to more than 200 articles in literature. Furthermore, their use as
      disease models was also studied signifying the versatility of iPSC lines.
      CONCLUSION: Through this review, we describe the advent of iPSC technology, where
      we comprehensively cover the generation of iPSCs and their characterization along
      with their prospective applications using IPSC banks in disease modeling and drug
      screening.

PMID- 28748764
TI  - Inflammatory biomarkers in atrial fibrillation.
AB  - During the last few years, a significant number of studies have attempted to
      clarify the underlying mechanisms that lead to the presentation of atrial
      fibrillation (AF). Inflammation is a key component of the pathophysiological
      processes that lead to the development of AF; the amplification of inflammatory
      pathways triggers AF, and, in tandem, AF increases the inflammatory state.
      Indeed, the plasma levels of several inflammatory biomarkers are elevated in
      patients with AF. In addition, the levels of specific inflammatory biomarkers may
      provide information regarding to the AF duration. Several small studies have
      assessed the role of anti-inflammatory treatment in atrial fibrillation but the
      results have been contradictory. Large-scale studies are needed to evaluate the
      role of inflammation in AF and whether anti-inflammatory medications should be
      routinely administered to patients with AF.

PMID- 28748765
TI  - Biomarkers in aortic valve stenosis and their clinical significance in
      transcatheter aortic valve implantation.
AB  - Aortic valve stenosis is one of the most common valvular heart disorders and the
      prevalence will rise as the population ages. Once symptomatic, patients with
      aortic valve stenosis tend to fare worse with high mortality rates. Aortic valve
      replacement is indicated in these patients and besides the standard surgical
      replacement; a less invasive approach, transcatheter aortic valve implantation,
      has gained momentum and has showed promising and solid results in patients with
      high surgical risk. An important aspect of evaluating patients with aortic valve
      stenosis is the ability to choose the best possible candidate for the procedure.
      In addition, predicting the short and long-term clinical outcomes after the valve
      replacement could offer the treating physicians a better insight and provide
      information for optimal therapy. Biomarkers are biological parameters that can be
      objectively measured and evaluated as indicators of normal biological processes
      and are easily monitored. The aim of this review is to critically assess some of
      the most widely used biomarkers at present (natriuretic peptides, troponins, C
      reactive protein) and provide an insight in novel biomarkers that are currently
      being investigated (galectin-3, growth differentiation factor-15, microRNAs) for
      possible diagnostic and prognostic use in aortic valve stenosis and transcatheter
      aortic valve implantation respectively.

PMID- 28748766
TI  - Atrial Fibrillation: Biomarkers determining prognosis.
AB  - Atrial fibrillation (AF) is a common cardiac arrhythmia known to incite increased
      thromboembolic and mortality risks, especially among patients not under
      anticoagulant therapy when that is indicated. Several routine scores exist to
      help stratify AF patients, such as the CHAD2DS2-VASc score and upon which
      physicians are based to decide whether to administer anticoagulant therapy. Being
      that anticoagulant regimen is a double-edged situation with both benefits and
      risks, decision-making process demands a definite and reliable, evidence-based
      set of data to rely on. Blood-based biological elements known as biomarkers are
      measurable indices that can provide crucial insights concerning not only
      underlying disease mechanisms but also prognostic and risk stratifying
      information. As AF is constituted by an overwhelming range of pathophysiological
      aspects such as inflammation, fibrosis, hypercoagulable states and myocardial
      damage, identifying and assessing relevant biomarkers will evidently support the
      clinician's prognostication efforts. The current review is directed into
      presenting studied biomarkers with proven prognostic potential in AF as well as
      possible enhancement of risk-scores when incorporated to them.

PMID- 28748767
TI  - Electrochemical Immunosensors for Disease Detection and Diagnosis.
AB  - BACKGROUND: The detection of biological molecules referred as biomarkers in
      biological fluids is fundamental in clinical analysis because it permits to
      discriminate between healthy and ill individuals and to evaluate the progress of
      a disease. The development of immunosensors for the detection and monitoring of
      biomarkers is currently a major area of research and, as more markers are
      discovered and their role in disease becomes better understood, this will
      continue to grow. METHODS: We report the research progresses of electrochemical
      immunosensor applied in clinical analysis that have been published in the last
      three years. RESULTS: The emphasis of this review is on the advances of the
      electrochemical immunosensors for detection and monitoring of cancerous,
      cardiovascular and neurological diseases. An immunosensor overview was presented
      as well as the biomarkers and biosensing systems currently used to detect the
      onset and monitor the progression of the mentioned diseases. CONCLUSIONS:
      Electrochemical biosensors focusing on a vast repertoire of analytes are now
      becoming one of the most widely explored scientific fields. This is due to their
      enormous potential in clinical diagnosis and biological process monitoring. In
      the near future, with the development of transducer technology, nano-sized
      material technology, and biomolecules engineering technology, biosensors should
      be powerful tools in several analytical areas.

PMID- 28748768
TI  - Allosteric Targeting of Aurora A Kinase Using Small Molecules: A Step Forward
      Towards Next Generation Medicines?
AB  - Aurora A (AurA) kinase is a key mitotic protein essential for carrying out
      numerous cellular functions. Overexpression or malfunction of this enzyme results
      in numerous human diseases most notably in cancer. Several small molecule
      inhibitors targeting the ATP binding site of this enzyme are in various stages of
      clinical development. However, ATP binding site inhibitors can result in
      selectivity problems often leading to undesirable off-target effects. Moreover,
      these drugs are prone to drug resistance problem rendering them unfit for long
      term administration. Allosteric inhibition of kinases using small molecules is an
      alternative strategy to target these enzymes and these could serve as the seeds
      for next generation medicines and minimize any selectivity problems associated
      with ATP binding site inhibitors. This review discusses the developments in the
      non-ATP site binding small molecule inhibitors of AurA and their prospect as
      future therapeutics and tools for chemical biology.

PMID- 28748769
TI  - The Role of Victimization in Shaping Households' Preparedness for Armed Conflicts
      in Israel.
AB  - OBJECTIVES: One of the most prominent threats to the Israeli population is the
      risk from armed conflicts. Yet, promoting preparedness behavior proves to be
      highly difficult. Arguably, this is partially due to the chronic exposure of the
      Israeli public to this threat, a.k.a. "Victimization." The purpose of this study
      was to examine whether victimization plays a prominent role in shaping
      preparedness behavior toward armed conflicts in Israel. METHODS: An online survey
      of 502 participants representing the adult Jewish population in Israel was
      carried out. A set of questionnaires designed to assess public perception of
      preparedness-affecting factors was used. The list of preparedness-affecting
      factors was conceptualized by an expert panel before the survey. RESULTS: The
      results suggest that low prioritization and ignoring of civil-defense
      instructions during routine times are leading causes for non-compliance with
      preparedness recommendations. Ignoring instructions is also negatively correlated
      with reported preparedness. Misunderstanding the threat and fearing it also seem
      to be important factors. CONCLUSIONS: The results of this study support the
      hypothesis that victimization plays an important role in shaping preparedness
      behavior toward armed conflicts among Jews in Israel. The findings demonstrate
      the complexity of the socio-psychological perspective of preparedness behavior in
      victimized populations. (Disaster Med Public Health Preparedness. 2018;12:67-75).

PMID- 28748770
TI  - Management of Diabetic Surgical Patients in a Deployed Field Hospital: A Model
      for Acute Non-Communicable Disease Care in Disaster.
AB  - Sudden onset disasters (SODs) have affected over 1.5 billion of the world's
      population in the past decade. During the same time, developing nations have
      faced a sustained increase in the burden of non-communicable disease (NCD) with
      extra pressure placed on health systems. The combined increase in SODs and the
      NCD epidemic facing the world's most disaster-prone nations will present new
      challenges to emergency medical teams (EMTs) during disaster response. This
      report details the experience as an EMT during the Typhoon Haiyan disaster of
      2013, with particular reference to the challenges of diabetic management in a
      surgical field hospital. The incidence of diabetes in this surgical cohort
      exceeded that of the population by a factor of four. The steps to prepare for and
      treat diabetes in the field provide a useful model for the management of NCD in
      the deployed field hospital environment after a disaster. McDermott KM ,
      Hardstaff RM , Alpen S , Read DJ , Coatsworth NR . Management of diabetic
      surgical patients in a deployed field hospital: a model for acute non
      communicable disease care in disaster. Prehosp Disaster Med. 2017;32(6):657-661.

PMID- 28748771
TI  - Acute Care Referral Systems in Liberia: Transfer and Referral Capabilities in a
      Low-Income Country.
AB  - : Introduction Following two decades of armed conflict in Liberia, over 95% of
      health care facilities were partially or completely destroyed. Although the
      Liberian health system has undergone significant rehabilitation, one particular
      weakness is the lack of organized systems for referral and prehospital care.
      Acute care referral systems are a critical component of effective health care
      delivery and have led to improved quality of care and patient outcomes. Problem
      This study aimed to characterize the referral and transfer systems in the largest
      county of Liberia. METHODS: A cross-sectional, health referral survey of a
      representative sample of health facilities in Montserrado County, Liberia was
      performed. A systematic random sample of all primary health care (PHC) clinics,
      fraction proportional to district population size, and all secondary and tertiary
      health facilities were included in the study sample. Collected data included
      baseline information about the health facility, patient flow, and qualitative and
      quantitative data regarding referral practices. RESULTS: A total of 62 health
      facilities-41 PHC clinics, 11 health centers (HCs), and 10 referral hospitals
      (RHs)-were surveyed during the 6-week study period. In sum, three percent of
      patients were referred to a higher-level of care. Communication between health
      facilities was largely unsystematic, with lack of specific protocols (n=3; 5.0%)
      and standardized documentation (n=26; 44.0%) for referral. While most health
      facilities reported walking as the primary means by which patients presented to
      initial health facilities (n=50; 81.0%), private vehicles, including commercial
      taxis (n=37; 60.0%), were the primary transport mechanism for referral of
      patients between health facilities. CONCLUSION: This study identified several
      weaknesses in acute care referral systems in Liberia, including lack of
      systematic care protocols for transfer, documentation, communication, and
      transport. However, several informal, well-functioning mechanisms for referral
      exist and could serve as the basis for a more robust system. Well-integrated
      acute care referral systems in low-income countries, like Liberia, may help to
      mitigate future public health crises by augmenting a country's capacity for
      emergency preparedness. Kim J , Barreix M , Babcock C , Bills CB . Acute care
      referral systems in Liberia: transfer and referral capabilities in a low-income
      country. Prehosp Disaster Med. 2017;32(6):642-650.

PMID- 28748772
TI  - Epidemiology and hospital readmission associated with complications of
      Staphylococcus aureus bacteremia in pediatrics over a 25-year period.
AB  - We sought to comprehensively assess the prevalence and outcomes of complications
      associated with Staphylococcus aureus bacteremia (SAB) in children. Secondarily,
      prevalence of methicillin resistance and outcomes of complications from
      methicillin-resistant S. aureus (MRSA) vs. methicillin-susceptible S. aureus SAB
      were assessed. This is a single-center cross-sectional study of 376 patients ?18
      years old with SAB in 1990-2014. Overall, 197 (52%) patients experienced
      complications, the most common being osteomyelitis (33%), skin and soft tissue
      infection (31%), and pneumonia (25%). Patients with complications were older
      (median 3 vs. 0.7 years, P = 0.05) and more had community-associated SAB (66% vs.
      34%, P = 0.001). Fewer patients with complications had a SAB-related emergency
      department or hospital readmission (10% vs. 19%, P = 0.014). Prevalence of
      methicillin resistance increased from 1990-1999 to 2000-2009, but decreased in
      2010-2014. Complicated MRSA bacteremia resulted in more intensive care unit
      admissions (66% vs. 47%, P = 0.03) and led to increased likelihood of having ?2
      foci (58% vs. 26%, P < 0.001). From multivariate analysis, community-associated
      SAB increased risk and concurrent infections decreased risk of complications
      (odds ratio (OR) 1.82 (1.1-3.02), P = 0.021) and (OR 0.58 (0.34-0.97), P =
      0.038), respectively. In conclusion, children with SAB should be carefully
      evaluated for complications. Methicillin resistance remains associated with poor
      outcomes but have decreased in overall prevalence.

PMID- 28748773
TI  - Differentiation between wild-type and vaccines strains of varicella zoster virus
      (VZV) based on four single nucleotide polymorphisms.
AB  - Varicella-zoster virus (VZV) infection (chickenpox) results in latency and
      subsequent reactivation manifests as shingles. Effective attenuated vaccines
      (vOka) are available for prevention of both illnesses. In this study, an amplicon
      based sequencing method capable of differentiating between VZV wild-type (wt)
      strains and vOka vaccine is described. A total of 44 vesicular fluid specimens
      collected from 43 patients (16 from China and 27 from the UK) with either
      chickenpox or shingles were investigated, of which 10 had received previous
      vaccination. Four sets of polymerase chain reactions were set up simultaneously
      with primers amplifying regions encompassing four single nucleotide polymorphisms
      (SNPs), '69349-106262-107252-108111'. Nucleotide sequences were generated by
      Sanger sequencing. All samples except one had a wt SNP profile of 'A-T-T-T'. The
      sample collected from a patient who received vaccine 7-10 days ago, along with
      VZV vaccine preparations, Zostavax and Baike-varicella gave a SNP profile 'G-C-C
      C'. The results show that this method can distinguish vaccine-derived virus from
      wt viruses from main four clades, (clades 1-4) and should be of utility
      worldwide.

PMID- 28748774
TI  - Exposure to parental psychopathology and offspring's risk of suicide-related
      thoughts and behaviours: a systematic review.
AB  - AIMS: The primary objective of this systematic review was to identify and
      synthesise analytic studies examining the association between exposure to
      parental psychopathology in childhood and the nature of subsequent suicide
      related thoughts (SRT) and suicide-related behaviour (SRB) (severity of ideation,
      planned/unplanned attempts/lethality) and to describe the direction, and
      magnitude of associations. The secondary objective was to determine if the
      associations from the primary objective differ by the type(s) and timing of
      parental psychopathology, sex/gender of the parent and child and is mediated by
      child psychiatric symptoms and family functioning. METHODS: A systematic review
      was conducted using guidelines from the PRISMA statement. MEDLINE, CINAHL,
      EMBASE, psycINFO, Web of Science and grey literature sources were searched by two
      reviewers to March, 2017. Studies were included if they examined any parental
      psychopathology (Diagnostic and Statistical Manual of Mental Disorders criteria
      or equivalent) or SRT or SRB and offspring SRT or SRB occurring from birth <25
      years of age. RESULTS: Out of 10 231 studies identified, 54 were included for
      review. Studies were clinically and methodologically heterogeneous with none at
      low risk of bias (ROB). Nine studies with moderate ROB indicated a significantly
      increased risk of offspring SRT, suicide attempts (SA) and suicide among those
      exposed to maternal SA and suicide in childhood or adolescence. In the remaining
      45 studies with higher ROB this association persisted. Several studies (67%) did
      not confirm that the exposure occurred in the offspring's childhood or
      adolescence. Findings were suggestive of a mediating effect of offspring
      psychiatric symptoms, however, few studies examined mediation and effect
      modification of contextual variables. CONCLUSIONS: Offspring exposed to maternal
      SA are at an increased risk of these same behaviours early in life. Prospective
      attention to the types and timing of maternal and paternal psychopathology and
      the intermediate pathways to offspring SRT and SRB onset is needed and could have
      implications for informing modifiable targets for early intervention and
      prevention.

PMID- 28748775
TI  - Reduction in extrapulmonary tuberculosis in context of antiretroviral therapy
      scale-up in rural South Africa.
AB  - Scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV)
      infection has reduced the incidence of pulmonary tuberculosis (PTB) in South
      Africa. Despite the strong association of HIV infection with extrapulmonary
      tuberculosis (EPTB), the effect of ART on the epidemiology of EPTB remains
      undocumented. We conducted a retrospective record review of patients initiated on
      treatment for EPTB in 2009 (ART coverage <5%) and 2013 (ART coverage 41%) at four
      public hospitals in rural Mopani District, South Africa. Data were obtained from
      TB registers and patients' clinical records. There was a 13% decrease in overall
      number of TB cases, which was similar for cases registered as EPTB (n = 399 in
      2009 vs. 336 in 2013; P < 0.01) and for PTB (1031 vs. 896; P < 0.01). Among EPTB
      cases, the proportion of miliary TB and disseminated TB decreased significantly
      (both P < 0.01), TB meningitis and TB of bones increased significantly (P < 0.01
      and P = 0.02, respectively) and TB pleural effusion and lymphadenopathy remained
      the same. This study shows a reduction of EPTB cases that is similar to that of
      PTB in the context of the ART scale-up. The changing profile of EPTB warrants
      attention of healthcare workers.

PMID- 28748776
TI  - Knowledge, Attitudes, and Practices among Members of Households Actively
      Monitored or Quarantined to Prevent Transmission of Ebola Virus Disease - Margibi
      County, Liberia: February-March 2015.
AB  - BACKGROUND: In early 2015, a patient from a cluster of cases of Ebola Virus
      Disease (EVD) in Monrovia, Liberia traveled to a rural village in Margibi County,
      potentially exposing numerous persons. The patient died in the village and post
      mortem testing confirmed Ebola Virus infection. Problem The Margibi County Health
      Team (CHT; Kakata, Margibi, Liberia) needed to prevent further transmission of
      EVD within and outside of the affected villages, and they needed to better
      understand the factors that support or impede compliance with measures to stop
      the spread of EVD. METHODS: In February-March 2015, the Margibi CHT instituted a
      21-day quarantine and active monitoring for two villages where the patient had
      contact with numerous residents, and a 21-day active monitoring for five other
      villages where the patient had possible contact with an unknown number of
      persons. One contact developed EVD and quarantine was extended an additional 12
      days in one village. In April 2015, the Margibi CHT conducted a household-based
      EVD knowledge, attitudes, and practices (KAP) survey of the seven villages. From
      April 24-29, 2015, interview teams approached every household in the seven
      villages and collected information on demographics, knowledge of EVD, attitudes
      about quarantine to prevent the spread of EVD, and their quarantine experiences
      and practices. Descriptive statistics were calculated. RESULTS: One hundred
      fifteen interviews were conducted, representing the majority of the households in
      the seven villages. Most (99%) correctly identified touching an infected person's
      body fluids and contact with the body of someone who has died from EVD as
      transmission routes. However, interviewees sometimes incorrectly identified
      mosquito bites (58%) and airborne spread (32%) as routes of EVD transmission, and
      72% incorrectly identified the longest EVD incubation period as <=seven days.
      Eight of 16 households in the two quarantined villages (50%) reported times when
      there was not enough water or food during quarantine. Nine of 16 (56%) reported
      that a household member had illnesses or injuries during quarantine; of these,
      all (100%) obtained care from a clinic, hospital, or Ebola treatment unit (ETU).
      CONCLUSION: Residents' knowledge of EVD transmission routes and incubation period
      were suboptimal. Public health authorities should consider assessing residents'
      understanding of Ebola transmission routes and effectively educate them to ensure
      correct understanding. Quarantined residents should be provided with sufficient
      food, water, and access to medical care. Wilken JA , Pordell P , Goode B , Jarteh
      R , Miller Z , Saygar BG Sr. , Maximore L , Borbor WM , Carmue M , Walker GW ,
      Yeiah A . Knowledge, attitudes, and practices among members of households
      actively monitored or quarantined to prevent transmission of Ebola Virus Disease 
      Margibi County, Liberia: February-March 2015. Prehosp Disaster Med.
      2017;32(6):673-678.

PMID- 28748777
TI  - Reflection on Lessons Learned: An Analysis of the Adverse Outcomes Observed
      During the Hurricane Rita Evacuation.
AB  - In September 2005, nearly 3.7 million people evacuated the Texas coastline in
      advance of Hurricane Rita's landfall, making the event the largest emergency
      evacuation in US history. The Rita evacuation underscored the importance of
      planning for domestic mass-evacuation events, as the evacuation itself led to
      over 100 of the at least 119 deaths attributed to the storm. In the days
      preceding Rita's landfall, several cascading, interrelated circumstances
      precipitated such adverse outcomes. This article explores the series of events
      leading up to the evacuation's poor outcomes, the response following Rita to
      amend evacuation plans, and how Texas successfully implemented these changes
      during later storms to achieve better outcomes. (Disaster Med Public Health
      Preparedness. 2018;12:115-120).

PMID- 28748778
TI  - WADEM Climate Change Position Statement.

PMID- 28748779
TI  - Disaster Metrics: A Comprehensive Framework for Disaster Evaluation Typologies
      CORRIGENDUM.

PMID- 28748780
TI  - miR-133a-3p Targets SUMO-Specific Protease 1 to Inhibit Cell Proliferation and
      Cell Cycle Progress in Colorectal Cancer.
AB  - Dysregulation of SUMO-specific protease 1 (SENP1) expression has been reported in
      several kinds of cancer, including human colorectal and prostate cancers,
      proposing SENP1 as an oncogene with a critical role in cancer progression. miR
      133a-3p has been reported as a tumor suppressor in several malignant neoplasias.
      However, the precise molecular mechanisms underlying its role in colorectal
      cancer remain largely unknown. The aim of this work was to investigate the
      relationship between miR-133a-3p and SENP1 in colorectal cancer cells. We found
      that miR-133a-3p expression was downregulated in colorectal cancer tissues. In
      silico analyses indicated that SENP1 is one of the target genes of miR-133a-3p.
      Overexpression of miR-133a-3p mimics was able to inhibit cell growth with G1
      arrest of colorectal cancer cells. Overexpression of miR-133a-3p antisense
      promoted cell growth of colorectal cancer cells. The luciferase reporter
      experiments showed that miR-133a-3p regulated the expression of SENP1 by
      combining with its 3'-UTR and resulted in downregulation of SENP1 and
      upregulation of CDK inhibitors such as p16, p19, p21, and p27. These results
      suggest that the miR-133a-3p-SENP1 axis might play a role in cell proliferation
      and cell cycle regulation of colorectal cancer cells.

PMID- 28748781
TI  - A Versatile Liquid Chromatographic Method for the Simultaneous Determination of
      Metformin, Sitagliptin, Simvastatin, and Ezetimibe in Different Dosage Forms.
AB  - A new LC method is introduced with the concept of its versatile application to
      widely used drugs from different pharmacological classes. Metformin hydrochloride
      (MTF), sitagliptin phosphate (SIT), simvastatin (SIM) and ezetimibe (EZB) were
      simultaneously determined with a simple reversed-phase LC method in which a SIT
      SIM binary mixture, present in a dosage form brand, was considered central for
      its development. Chromatographic separation was achieved with a mobile phase of
      acetonitrile and 0.02 M potassium dihydrogen phosphate (pH 5.2) (77 + 23, v/v)
      flowing through a C18 column (BDS Hypersil, 250 * 4.6 mm, 5 um) at 1.2 mL/min at
      ambient temperature. UV detection was programmed to be carried out at 210 nm for
      EZB, SIT, and MTF, whereas SIM was detected at 240 nm. The method was validated
      according to International Conference on Harmonization guidelines. Linearity,
      accuracy, and precision were satisfactory over concentration ranges 4-40 ug/mL
      for EZB and SIM, 0.5-50 ug/mL for SIT, and 5-500 ug/mL for MTF. Coefficients of
      determination were >0.99 for the four drugs. LOQs found were 0.01 ug/mL for EZB,
      0.02 ug/mL for SIT, 0.2 ug/mL for MTF, and 0.02 ug/mL for SIM. The developed
      method is simple, rapid, accurate, precise, and suitable for the routine QC
      analysis of the cited drugs in pharmaceutical products by conventional HPLC
      systems.

PMID- 28748782
TI  - Dengue Virus Exported from Cote d'Ivoire to Japan, June 2017.
AB  - Since April 2017, a dengue fever outbreak has been ongoing in Cote d'Ivoire. We
      diagnosed dengue fever (type 2 virus) in a traveler returning to Japan from Cote
      d'Ivoire. Phylogenetic analysis revealed strain homology with the Burkina Faso
      2016 strain. This case may serve as an alert to possible disease spread outside
      Africa.

PMID- 28748784
TI  - Testosterone and Aggression: More Than Just Biology?

PMID- 28748783
TI  - Detection of Echinococcus multilocularis and other foodborne parasites in fox,
      cat and dog faeces collected in kitchen gardens in a highly endemic area for
      alveolar echinococcosis.
AB  - Echinococcus multilocularis, Toxoplasma gondii and Toxocara spp. are foodborne
      parasites whose eggs or oocysts are spread in the environment via canid or felid
      faeces. They can cause infections in humans following the raw consumption of
      contaminated fruit or vegetables. In this study, their occurrence was
      investigated by quantitative polymerase chain reaction (qPCR) in 254 carnivore
      faeces deposited in 94 kitchen gardens of northeastern France that were sampled
      between two and six times from October 2011 to April 2013. Less than 25% of the
      sampled kitchen gardens contained more than 75% of the collected faeces. Of the
      219 faeces that could be attributed to an emitter, cat accounted for 58%, fox for
      32% and dog for 10%. Echinococcus multilocularis was detected in 35%, 11% and 7%
      of fox, dog and cat faeces, respectively, and Toxocara spp. in 33%, 12% and 5.5%
      of cat, fox and dog faeces, respectively. Toxoplasma gondii was detected in 2/125
      cat faeces and 2/21 dog faeces. The 34 faeces that tested positive for E.
      multilocularis were found in only 19 out of the 94 sampled kitchen gardens, and
      the 40 faeces that tested positive for Toxocara spp. were found in 28 of them.
      Consequently, some kitchen gardens appeared particularly at risk of human
      exposure to foodborne parasites, including E. multilocularis responsible for
      alveolar echinococcosis (AE), which is a serious zoonosis. In endemic areas,
      kitchen garden owners should be informed about the zoonotic risk linked to
      carnivore faeces deposits and encouraged to set up preventive measures.

PMID- 28748785
TI  - Striatal 5-HT1B Receptors and Aggression.

PMID- 28748786
TI  - How Does Adversity "Get Under the Skin" to Lead to the Development of Antisocial
      Behavior?

PMID- 28748787
TI  - Scanning for Justice With Functional Magnetic Resonance Imaging.

PMID- 28748789
TI  - Content and discontent: editing a psychiatry journal.

PMID- 28748788
TI  - Reward Mechanisms Across Aggressive and Addictive Forms of Externalizing
      Psychopathology.

PMID- 28748790
TI  - Antipsychotic treatment of children and adolescents is a double-edged sword.

PMID- 28748791
TI  - Meta-community mental health care: towards a new concept.

PMID- 28748792
TI  - Corrections.

PMID- 28748793
TI  - Corrections.

PMID- 28748794
TI  - Towards a mental health inequity audit.

PMID- 28748795
TI  - A call for parenting interventions for refugee mothers with children younger than
      3 years.

PMID- 28748796
TI  - Contributions of immigrants to the field of US psychiatry.

PMID- 28748799
TI  - Celso Arango: early intervention for the best prevention.

PMID- 28748797
TI  - Should the Government change the Mental Health Act or fund more psychiatric beds?

PMID- 28748800
TI  - REMS, a new chapter in Italian psychiatry.

PMID- 28748801
TI  - Antipsychotics in adolescent-onset psychosis: a work in progress.

PMID- 28748802
TI  - Regionalising without rationalising in the Greek mental health care system.

PMID- 28748804
TI  - Culture and psychotherapy in Japan.

PMID- 28748803
TI  - Serial MRI Scan of Posterior Fossa Tumours Predict Patients at Risk of Developing
      Neurocognitive Impairment
AB  - Background: Brain tumours are the most common solid tumours in children. More
      than 50% of these tumoursdevelop in the posterior cranial fossa. Long term
      survivors of posterior fossa tumours (PFT) suffer from neurocognitiveand memory
      issues. We hypothesized that serial MRI scanning of brain would show differences
      in hippocampal andACC volume change in PFT patients treated with and without
      chemo-radiotherapy. Material and Methods: Twelvepatients (8 females and 4 males)
      underwent 76 serial MR imaging examinations before and during treatment for
      posteriorfossa tumours. Seven patients (4 medulloblastoma, 2 as ependymoma and 1
      high grade glioma) were treated withmaximum surgical resection followed by
      adjuvant radiotherapy and chemotherapy (Group 1). The other five patientswere
      diagnosed as pilocytic astrocytoma who were treated only with surgery (Group 2).
      Hippocampal volumes wereobtained manually on high-resolution 3Tesla T1-weighted
      images and normalised to intracranial volume, while ACCthickness and volume were
      obtained automatically using FreeSurfer software. Results: After the treatment
      period,the change in normalised hippocampal volume from baseline was
      significantly lower in group 1 patients compared togroup 2 (mean change 
      0.0001470 +/- 8.981e-005; Mean +/- SEM vs 0.0002765 +/- 9.151e-005; Mean +/- SEM,
      respectively,P=0.004). Displayed graphically, the negative hippocampal growth
      trajectory in group 1 gradually returned to a positivegrowth pattern. There were
      no statistically significant changes in ACC volume and thickness. Both groups had
      similarrates of pre-operative hydrocephalus. Conclusion: Compared to PFT patients
      treated with surgery alone, PFT patientstreated with chemo-radiotherapy showed
      lower hippocampal volumes and altered hippocampal growth trajectory.Serial
      quantitative MRI measures of brain may provide a neuroanatomical substrate for
      assessing functional impacton normal brain function following treatment of
      posterior fossa tumours.

PMID- 28748805
TI  - Notice of Correction.

PMID- 28748806
TI  - Clinical trial research in focus: rethinking trials in sepsis.

PMID- 28748807
TI  - Urban biodiversity affects children's respiratory health.

PMID- 28748809
TI  - Corrections.

PMID- 28748808
TI  - Potential and challenges of serotherapy for severe influenza.

PMID- 28748810
TI  - Corrections.

PMID- 28748811
TI  - The Obesity Paradox-What Does It Mean for Lung Cancer Surgery?

PMID- 28748812
TI  - The Financial Implications of Lung Cancer Screening: Is It Worth It?

PMID- 28748813
TI  - METex14-Positive NSCLC: Time to Take the Therapy to the Target to Aim for a Cure?

PMID- 28748814
TI  - Robert Comis, MD, The Passing of a "Lung Man".

PMID- 28748815
TI  - Erratum.

PMID- 28748816
TI  - Pericardial Tamponade Caused by a Hypersensitivity Response to Tuberculosis
      Reactivation after Anti-PD-1 Treatment in a Patient with Advanced Pulmonary
      Adenocarcinoma.

PMID- 28748817
TI  - Numb Chin Syndrome: An Ominous Sign of Lung Cancer.

PMID- 28748818
TI  - FISH Analysis of Crizotinib Target Genes ROS1/ALK/MET in Malignant Mesothelioma.

PMID- 28748819
TI  - Osimertinib-Induced Interstitial Lung Disease Presenting as Eosinophilic
      Pneumonia.

PMID- 28748820
TI  - Pulmonary Adenocarcinoma with Enteric Differentiation Presenting with
      Bronchorrhea.

PMID- 28748821
TI  - Chronic Cholestasis with Dilation of Intrahepatic Bile Duct Related to
      Administration of Ceritinib.

PMID- 28748822
TI  - Reframing the Concept of "No Treatment" in Advanced NSCLC.

PMID- 28748823
TI  - Response to "Reframing the Concept of 'No Treatment' in Advanced NSCLC".

PMID- 28748824
TI  - Questions Regarding "CD74-ROS1 Fusion in NSCLC Detected by Hybrid Capture-Based
      Tissue Genomic Profiling and ctDNA Assays".

PMID- 28748825
TI  - A Case of Heart Failure after Treatment with Anti-PD-1 Antibody Followed by
      Adoptive Transfer of Cytokine-Activated Killer Cells in a Recurrent Lung Cancer
      Patient.

PMID- 28748826
TI  - Smoking History Predicts Sensitivity to PARP Inhibitor Veliparib in Patients with
      Advanced Non-Small Cell Lung Cancer: Methodological Issues.

PMID- 28748827
TI  - Concern: Improving the Accuracy of Mesothelioma Diagnosis in China.

PMID- 28748828
TI  - Improving the Accuracy of Mesothelioma Diagnosis in China.

PMID- 28748829
TI  - Dose assessment following an overexposure of a worker at a Swiss nuclear power
      plant.
AB  - AIM: The aim of this work was to assess the doses received by a diver exposed to
      a radiation source during maintenance work in the fuel transfer pool at a Swiss
      nuclear power plant, and to define whether the statutory limit was breached or
      not. METHOD: Onsite measurements were carried out and different scenarios were
      simulated using the MicroShield Software and the MCNPX Monte Carlo radiation
      transport code to estimate the activity of the irradiating object as well as the
      doses to the limbs and the effective dose delivered to the operator. RESULTS: The
      activity of the object was estimated to 1.8 TBq. From the various dose
      estimations, a conservative value of 7.5 Sv was proposed for the equivalent dose
      to the skin on the hands and an effective dose of 28 mSv. CONCLUSION: The use of
      different experimental and calculation methods allowed us to accurately estimate
      the activity of the object and the dose delivered to the diver, useful
      information for making a decision on the most appropriate scheme of follow up for
      the patient.

PMID- 28748830
TI  - A neural network with central pattern generators entrained by sensory feedback
      controls walking of a bipedal model.
AB  - A neuromechanical simulation of a planar, bipedal walking robot has been
      developed. It is constructed as a simplified, planar musculoskeletal model of the
      biomechanics of the human lower body. The controller consists of a dynamic neural
      network with central pattern generators (CPGs) entrained by force and movement
      sensory feedback to generate appropriate muscle forces for walking. The CPG model
      is a two-level architecture, which consists of separate rhythm generator and
      pattern formation networks. The biped model walks stably in the sagittal plane
      without inertial sensors or a centralized posture controller or a 'baby walker'
      to help overcome gravity. Its gait is similar to humans' and it walks at speeds
      from 0.850 m s-1 up to 1.289 m s-1 with leg length of 0.84 m. The model walks
      over small unknown steps (6% of leg length) and up and down 5 degrees  slopes
      without any additional higher level control actions.

PMID- 28748831
TI  - Investigation of the superconducting gap structure in kappa-(BEDT-TTF)2Cu(NCS)2
      and kappa-(BEDT-TTF)2Cu[N(CN)2]Br by means of thermal-conductivity measurements.
AB  - We report temperature-dependent thermal-conductivity, kappa, measurements on the
      layered quasi-two-dimensional organic superconductors kappa-(BEDT-TTF)2Cu(NCS)2
      and kappa-(BEDT-TTF)2Cu[N(CN)2]Br down to 160 mK. The results for kappa-(BEDT
      TTF)2Cu(NCS)2 may be consistent with a nodal superconducting (SC) gap structure
      as indicated by a non-negligible remnant linear contribution when [Formula: see
      text] is extrapolated to [Formula: see text]. For kappa-(BEDT-TTF)2Cu[N(CN)2]Br,
      contrary to expectations, higher kappa values are observed in the superconducting
      regime as compared to the normal, high-field state evidencing a dominant phonon
      contribution to kappa in the superconducting state. The strong increase of kappa
      in the normal state below T c for both samples indicates strong electron-phonon
      scattering. Our results highlight the need for thermal-conductivity measurements
      performed down to significantly lower temperatures to determine the symmetry of
      the SC gap.

PMID- 28748832
TI  - Temporo-spatial distribution of insecticide-resistance in Indian malaria vectors
      in the last quarter-century: Need for regular resistance monitoring and
      management.
AB  - The Indian vector control programme similar to other programmes in the world is
      still reliant on chemical insecticides. Anopheles culicifacies is the major
      vector out of six primary malaria vectors in India and alone contributes about
      2/3 malaria cases annually; and per se its control is actually control of malaria
      in India. For effective management of vectors, current information on their
      susceptibility status to different insecticides is essential. In this review, an
      attempt was made to compile and present the available data on the susceptibility
      status of different malaria vector species in India from the last 2.5 decades.
      Literature search was conducted by different means mainly web and library search;
      susceptibility data was collated from 62 sources for the nine malaria vector
      species from 145 districts in 21 states and two union territories between 1991
      and 2016. Interpretation of the susceptibility/resistance status was made on
      basis of the recent WHO criteria. Comprehensive analysis of the data indicated
      that An. culicifacies, a major vector species was resistant to at least one
      insecticide in 70% (101/145) of the districts. It was reported mostly resistant
      to DDT and malathion whereas, its resistant status against deltamethrin varied
      across the districts. The major threat for the malaria control programmes is
      multiple-insecticide-resistance in An. culicifacies which needs immediate
      attention for resistance management in order to sustain the gains achieved so
      far, as the programmes have targeted malaria elimination by 2030.

PMID- 28748833
TI  - Identification and characterization of differentially expressed genes from human
      microglial cell samples infected with Japanese encephalitis virus.
AB  - BACKGROUND & OBJECTIVES: Limited studies have been reported on Japanese
      encephalitis (JE) with reference to microarray data analysis. The present study
      involved an in silico approach for identification and characterization of
      differentially expressed genes in human microglial cell (CHME3) samples, infected
      with P20778 strain of Japanese encephalitis virus (JEV). METHODS: Gene expression
      data (GSE57330) belonging to mRNA expression profile of CHME3 cells infected with
      JEV, was downloaded from the gene expression omnibus (GEO) database, processed
      and normalized by robust multichip averaging (RMA) method using affy packages of
      R. The Bayes method was used to correct multiple testing. The log fold change
      (logFC > 1) and p< 0.05 were used as cut-off to identify differentially expressed
      genes (DEGs). The newly identified hub genes were set at the centre for
      construction of protein-protein interaction network using search tool for the
      retrieval of interacting genes/proteins (STRING) database considering human
      genome as reference. Gene ontology and pathway enrichment analysis of the hub
      gene and its associated genes were performed using STRING and DAVID tool.
      RESULTS: Microarray data analysis revealed that STAT1 gene was down-regulated
      during JEV infection. STAT1 gene was found to interact with tyrosine protein
      kinase family members, and showed strong interaction with JAK1 and JAK2 genes.
      INTERPRETATION & CONCLUSION: The identified transcription factors and the binding
      sites in the promoter region of STAT1 gene might act as potential drug targets in
      near future.

PMID- 28748834
TI  - Effect of L-arginine on the growth of Plasmodium falciparum and immune modulation
      of host cells.
AB  - BACKGROUND & OBJECTIVES: Malaria is a life-threatening disease caused by
      Plasmodium parasites. The life-cycle of Plasmodium species involves several
      stages both in mosquito and the vertebrate host. In the erythrocytic stage,
      Plasmodium resides inside the red blood cells (RBCs), where it meets most of its
      nutritional requirement by degrad- ing host's haemoglobin. L-arginine is required
      for growth and division of cells. The present study was aimed to demonstrate the
      effect of supplementation of different concentrations of L-arginine and L
      citrulline on the growth of parasite, and effect of the culture supernatant on
      the host's peripheral blood mononuclear cells (PBMCs). METHODS: To examine the
      effect of supplementation of L-arginine and L-citrulline, Plasmodium falciparum
      (3D7 strain) was cultured in RPMI 1640, L-arginine deficient RPMI 1640, and in
      different concentrations of L-arginine, and L-citrulline supplemented in arginine
      deficient RPMI 1640 medium. To have a holistic view of in vivo cell activation,
      the PBMCs isolated from healthy human host were cultured in the supernatant
      collected from P. falciparum culture. RESULTS: Growth of the parasite was greatly
      enhanced in L-arginine supplemented media and was found to be concentration
      dependent. However, parasite growth was compromised in L-citrulline supplemented
      and L-arginine deficient media. The supernatant collected from L-arginine
      supplemented parasite media (sArg) showed increased FOXP3 and interleukin-10 (IL
      10) expression as compared to the supernatant collected from L-citrulline supple-
      mented parasite media (sCit). INTERPRETATION & CONCLUSION: The in vitro culture
      results showed, decreased parasite growth, and decreased expression of programmed
      cell death-1 (PD-1) (a coinhibitory molecule) and IL-10 in the L-citrulline
      supplemented media as compared to L-arginine supplemented media. Hence, it was
      concluded that L-citrulline supplementation would be a better alternative than L
      arginine to inhibit the parasite growth.

PMID- 28748835
TI  - Prevalence of Lassa virus among rodents trapped in three South-South States of
      Nigeria.
AB  - BACKGROUND & OBJECTIVES: Lassa fever has been endemic in Nigeria since 1969. The
      rodent Mastomys natalensis has been widely claimed to be the reservoir host of
      the Lassa virus. This study was designed to investigate the dis- tribution of
      species of rodents in three states (Edo, Delta and Bayelsa) of Nigeria and to
      determine the prevalence of Lassa virus amongst trapped rodents in the selected
      states. METHODS: Rodents were trapped during November 2015 to October 2016 from
      the three states in South-South re- gion of Nigeria. Total RNA was extracted from
      the blood collected from the trapped rodents. Reverse transcription polymerase
      chain reaction (RT-PCR) was used to confirm the presence of Lassa virus in the
      rodents. RESULTS: The results revealed that six species of rodents were
      predominantly present in these geographical locations. Mus musculus (39.4%) had
      the highest prevalence, closely followed by Rattus rattus (36.1%), R. fuscipus
      (20.3%), M. natalensis (2%), Myosoricinae soricidae (1.2%) and R. norvegicus
      (1%). The overall positivity (carrier rate) of Lassa virus was 1.6% amongst the
      1500 rodents caught in the three states. In Edo and Delta States, the RT-PCR
      results showed presence of Lassa virus in R. rattus, M. musculus and M.
      natalensis. On the other hand, only M. na- talensis was detected with the virus,
      amongst the species of rodents caught in Bayelsa State. M. natalensis recorded
      the highest Lassa virus among rodents trapped in Edo (87%), Delta (50%) and
      Bayelsa (11%) States respectively. INTERPRETATION & CONCLUSION: The rather low
      Lassa virus positive among rodents in Bayelsa State of Nigeria may explain the
      absence of reports of outbreak of Lassa fever over the past 48 yr in the state.
      The results also confirmed that apart from Mastomys natalensis, other rodents
      such as Rattus rattus and Mus musculus may also serve as res- ervoirs for Lassa
      virus. From the findings of this cross-sectional study, it was concluded that a
      more comprehensive study on rodents as reservoir host, need to be undertaken
      across the entire states of Nigeria, for better understanding of the epidemiology
      and endemicity of Lassa fever.

PMID- 28748836
TI  - Morphometric and morphological appraisal of the eggs of Anopheles stephensi
      (Diptera: Culicidae) from India.
AB  - BACKGROUND & OBJECTIVES: Anopheles stephensi is one of the most important urban
      malaria vectors in India and contribute about 12% of total malaria cases. An.
      stephensi has three ecological variants; type, intermediate and mysorensis that
      can be differentiated on the basis of differences in number of ridges on egg
      float and on the basis of spiracular indices. Because of its anthropophilic
      nature the 'type' form is an efficient malaria vector. In the present study, the
      egg surface morphometry and morphology of An. stephensi 'type' form was studied
      and detail distinguish- ing characters were recorded for its correct
      identification. METHODS: Eggs of An. stephensi 'type' form were studied by
      scanning electron microscopy (SEM) after sputter- coating with gold. In total 23
      egg characters were analysed morphologically and morphometrically, which included
      egg attributes, deck attributes, ventral tubercles, micropyle and float
      attributes. RESULTS: The dorsal surface of the egg of 'type' form was curved
      while the ventral surface was concave and both anterior and posterior ends were
      blunt. The average length and width of egg was 473.94 + 11.18 and 154.69 + 2.66
      MUm respectively. The number of float ribs observed was 20.33 +/- 0.33. The
      maximum length of float was found to be 246.57 + 15.27 MUm, whereas maximum width
      was 87.16 + 3.83 MUm. INTERPRETATION & CONCLUSION: The present study has
      generated some important data which is specific to An. Stephensi 'type' form and
      provided significant morphological and morphometric standards for its correct
      identification. This information could be useful in differentiation of An.
      stephensi 'type' form from other ecological forms of the same species as well as
      other species of Anopheles.

PMID- 28748837
TI  - The seroprevalence of Coxiella burnetii in Erzincan, Turkey: Identification of
      the risk factors and their relationship with geographical features.
AB  - BACKGROUND & OBJECTIVES: Coxiella burnetii (C. burnetii) bacterium, the causative
      agent of Q fever has regained importance due to the increasing cases of
      infections and outbreaks. A cross-sectional descriptive study was conducted to
      investigate the seroprevalence of C. burnetii in human populations of Erzincan
      province located in the eastern Turkey, identify the risk factors, and to explore
      the relationship between geographical features. METHODS: A total of 368 people
      residing in the rural (306) and urban (62) areas of the province were included in
      the study. Serum samples were analyzed for the presence of C. burnetii phase II
      IgG antibody using ELISA (Virion/ Serion, Wurzburg, Germany). Spatial analyses
      were performed to evaluate correlations between seroprevalence and geographical
      features. RESULTS: The overall seroprevalence of C. burnetii was found to be 8.7%
      (32/368). In rural residents it was 8.5% (26/306), while in urban population it
      was 9.7% (6/62). Cattle breeding and contact with animal afterbirth waste were
      found to be major risk factors, and were significantly correlated with
      seropositive cases (p<0.05). The seropositive cases were only observed in the
      areas between 1067 and 1923 masl. Of the total seropositive cases, 65.6% were
      within 1000 m and 87.5% within 4000 m of rivers and their main tributaries.
      Around 59.4% cases were observed in areas with a slope of 0 to 5 degrees .
      INTERPRETATION & CONCLUSION: The results of the study showed that C. burnetii
      seroprevalence was higher than expected, and significantly differs according to
      geographical features of a region. Significant risk factors include raising
      cattle and exposure to infected animals or their birth products/secretions. It is
      also more frequent in areas with higher number of rivers and streams, higher
      altitude and lower slope.

PMID- 28748838
TI  - Larvicidal activity prediction against Aedes aegypti mosquito using computational
      tools.
AB  - BACKGROUND & OBJECTIVES: Aedes aegypti is an important vector for transmission of
      dengue, yellow fever, chikun- gunya, arthritis, and Zika fever. According to the
      World Health Organization, it is estimated that Ae. aegypti causes 50 million
      infections and 25,000 deaths per year. Use of larvicidal agents is one of the
      recommendations of health organizations to control mosquito populations and limit
      their distribution. The aim of present study was to deduce a mathematical model
      to predict the larvicidal action of chemical compounds, based on their structure.
      METHODS: A series of different compounds with experimental evidence of larvicidal
      activity were selected to develop a predictive model, using multiple linear
      regression and a genetic algorithm for the selection of variables, implemented in
      the QSARINS software. The model was assessed and validated using the OECDs
      principles. RESULTS: The best model showed good value for the determination
      coefficient (R2 = 0.752), and others parameters were appropriate for fitting (s =
      0.278 and RMSEtr = 0.261). The validation results confirmed that the model
      hasgood robustness (Q2LOO = 0.682) and stability (R2-Q2LOO = 0.070) with low
      correlation between the descriptors (KXX = 0.241), an excellent predictive power
      (R2 ext = 0.834) and was product of a non-random correlation R2 Y-scr = 0.100).
      INTERPRETATION & CONCLUSION: The present model shows better parameters than the
      models reported earlier in the literature, using the same dataset, indicating
      that the proposed computational tools are more efficient in identifying novel
      larvicidal compounds against Ae. aegypti.

PMID- 28748839
TI  - Seroprevalence of dengue in a rural and an urbanized village: A pilot study from
      rural western India.
AB  - BACKGROUND & OBJECTIVES: Dengue is highly prevalent in tropical and subtropical
      regions. The prevalence of dengue is influenced by number of factors, i.e. host,
      vector, virus and environmental conditions including urbanization and population
      density. A cross sectional study was undertaken to determine the seroprevalence
      of dengue in two selected villages that differed in the level of their
      urbanization and population density. METHODS: Two villages with demographically
      well-defined populations close to Pune, a metropolitan city of western India,
      were selected for the study. Age stratified serosurvey was carried out during
      February to May 2011 in the two villages-a rural village A, located 6 km from the
      national highway with a population density of 159/km2 ; and an urbanized village
      B, located along the highway with a population density of 779/km2 . Assuming a
      low seroposi- tivity of 10%, 702 serum samples were collected from village A.
      Sample size for village B was calculated on the basis of seropositivity obtained
      in village A, and 153 samples were collected. Serum samples were tested for the
      presence of dengue virus (DENV)-specific IgG. Simple proportional analyses were
      used to calculate and compare the seroprevalence. RESULTS: Of the 702 samples
      collected from village A, 42.8% were found positive for anti-DENV IgG. A
      significantly higher seropositivity for DENV (58.8%) was found in village B. In
      village A, there was an age dependent increase in seroprevalence; whereas, in
      village B, there was a steep increase from 17% positivity in 0-10 yr age group to
      72% in the 11-20 yr age group. The seroprevalence was almost similar in the older
      age groups. INTERPRETATION & CONCLUSION: The observations suggested that
      prevalence of dengue is probably associated with urbanization and host population
      density. Areas that are in the process of urbanization needs to be monitored for
      prevalence of dengue and its vector, and appropriate vector control measures may
      be implemented.

PMID- 28748840
TI  - Cardiovascular involvement in severe malaria: A prospective study in Ranchi,
      Jharkhand.
AB  - BACKGROUND & OBJECTIVES: Malaria is considered as the most important parasitic
      disease of humans, causing seri- ous illness that can be fatal, if not diagnosed
      and treated immediately. It is a multisystem disorder affecting nearly every
      system of the body. The aim of the present study was to evaluate the involvement
      of cardiovascular system in severe malaria using non-invasive methods. METHODS:
      This prospective study was conducted on patients of severe malaria who were
      admitted between June and November 2015 in the Department of Medicine, Rajendra
      Institute of Medical Sciences and Hospital, Ranchi, Jharkhand, India. A total of
      27 cases (18 males and 9 females; age ranging between 15 and 70 yr) of severe
      malaria (P. falciparum 24; P. vivax 1; mixed 2) were diagnosed by microscopic
      examination of peripheral blood smear and bivalent rapid diagnostic test (RDT)
      kit. The assessment of cardiovascular system was done by clinical examination,
      chest X-ray, ECG and transthoracic echocardiography. RESULTS: In all, 7 (26%)
      patients were found to be suffering from circulatory failure, out of which one
      was P. vivax case and rest were cases of P. falciparum infection with high
      parasite density. One patient died due to cardiovascular collapse. ECG revealed
      sinus bradycardia [Heart rate (HR): 40-60] in 7% of the cases, extreme
      tachycardia (HR: 120-150) in 3.7% of cases and premature arterial ectopic with
      tachycardia in 3.7% of patients (p <0.05). The echo- cardiographic findings were
      global hypokinesia with decreased left ventricular ejection fraction (<55%) in
      11.1%, grade 1 left ventricular diastolic dysfunction in 3.7%, mild tricuspid
      regurgitation (TR) with mild pulmonary artery hypertension (PAH) in 3.7% and mild
      pericardial effusion in 3.7% of the cases. The ECG and echocardiography changes
      indicated myocardial involvement in severe malaria. INTERPRETATION & CONCLUSION:
      The present study indicated involvement of cardiovascular system in severe
      malaria as evidenced from ECG and echocardiography. The study also revealed that
      cardiovascular instabilities are common in falciparum malaria, but can also be
      observed in vivax malaria.

PMID- 28748841
TI  - Prevalence of IgG antibodies for the West Nile virus in human population in
      Tripoli, Libya.
AB  - BACKGROUND & OBJECTIVES: West Nile fever (WNF) is a mosquito-borne viral
      infection, circulated in natural cycles between birds and mosquitoes,
      particularly Culex species. It is transmitted to humans through mosquito bites,
      and causes a variety of clinical outcomes, ranging from asymptomatic or mild
      febrile illness to severe men in go encepha- litis with some fatalities observed
      in older or immunocompromised patients. West Nile virus (WNV) transmission is
      considerably influenced by environmental conditions; and abundance of avifauna
      and mosquitoes.There are very few reports on WNV exposure in individuals from
      Tripoli City in Libya. The main objective was to provide basic epidemiological
      information about the WNV seroprevalence in the human population of Tripoli.
      METHODS: A total of 400 serum samples were collected from persons (123 females,
      277 males; age range: 15-78 yr) approaching the Tripoli Reference Laboratory for
      the purpose of obtaining health certificate; during the period from August to
      October 2013. The presence of WNV IgG antibodies was evaluated by a commercial
      kit based on WNV immunoglobulin G (IgG) enzyme-linked immunosorbent assay
      (ELISA). RESULTS: It was observed that 2.75% (11/400) samples were found reactive
      in the WNV ELISA assay. This result suggests that WNV has a low prevalence in the
      study area. INTERPRETATION & CONCLUSION: Seropositivity rates of WNV in Tripoli
      region of Libya were low. However, continu- ous monitoring of population is
      important to keep track of the disease prevalence, risk factors, reservoir hosts
      and vectors for better understaning of the disease epidemiology and designing
      appropriate control strategies.

PMID- 28748842
TI  - Separation, quantification and mosquito larvicidal activity of insecticidal
      crystal proteins of Bacillus thuringiensis var. israelensis (VCRC B17; MTCC
      5596).

PMID- 28748843
TI  - Concurrent mosquito-borne triple infections of dengue, malaria and chikungunya: A
      case report.

PMID- 28748844
TI  - Spotted fever rickettsiae and tuberculous meningitis dual infection presenting as
      acute encephalitis syndrome: A fatal case report.

PMID- 28748845
TI  - A case of Plasmodium vivax malaria presenting as acute cerebral infarct.

PMID- 28748846
TI  - Diets for Patients with Amyotrophic Lateral Sclerosis: Pay Attention to
      Nutritional Intervention.

PMID- 28748847
TI  - Clinical Features of Isolated Bulbar Palsy of Amyotrophic Lateral Sclerosis in
      Chinese Population.
AB  - BACKGROUND: Progressive bulbar palsy (PBP) is a classic phenotype of bulbar onset
      amyotrophic lateral sclerosis (ALS) with more rapid progression and worse
      prognosis. However, as an often under-understood variant of ALS, isolated bulbar
      palsy (IBP) appears to progress more slowly and has a relatively benign
      prognosis. This study aimed to investigate the natural course and clinical
      features of IBP in Chinese population and to compare them with those of PBP.
      METHODS: The clinical data of patients with bulbar onset ALS were collected from
      January 2009 to December 2013. Revised ALS Functional Rating Scale (ALSFRS-R),
      forced vital capacity (FVC), and follow-up evaluation were performed, and the
      differences in basic clinical features, ALSFRS-R, FVC, and primary outcome
      measures between IBP and PBP were analyzed. The independent t-test, Chi-square
      test, Mann-Whitney U-test, and Kaplan-Meier analysis were used. RESULTS: Totally
      154 patients with bulbar onset ALS were categorized into two groups, 33 with IBP
      and 121 with PBP. In the IBP group, the male to female ratio was 0.7 to 1.0, and
      the mean onset age was 58.5 years. The mean duration from the onset was 16.0
      months, and the mean ALSFRS-R score was 43.4 at patients' first visit to our
      hospital. In 14 IBP patients performing FVC examination, the mean FVC value was
      90.5% and there were only two cases with abnormal FVC. In 26 IBP patients
      completing follow-up, 15 (58%) suffered death or tracheotomy and the mean
      survival time was 40.5 months. Significant differences were noted in sex ratio,
      onset age, ALSFRS-R score, upper motor neuron limb signs, pure lower motor neuron
      (LMN) bulbar signs, FVC, and survival time between IBP and PBP. CONCLUSIONS: IBP
      was evidently different from PBP, which was characterized with the predominance
      of female, pure LMN bulbar signs, an older onset age, a relative preservation of
      respiratory function, and a better prognosis.

PMID- 28748848
TI  - Nine-hole Peg Test and Ten-meter Walk Test for Evaluating Functional Loss in
      Chinese Charcot-Marie-Tooth Disease.
AB  - BACKGROUND: The 9-hole peg test (9-HPT) and 10-meter walk test (10-MWT) are
      commonly used to test finger motor function and walking ability. The aim of this
      present study was to investigate the efficacy of these tests for evaluating
      functional loss in Chinese Charcot-Marie-Tooth (CMT) disease. METHODS: Thirty
      four Chinese CMT patients (CMT group) from August 2015 to December 2016 were
      evaluated with 9-HPT, 10-MWT, CMT disease examination score, overall neuropathy
      limitation scale (ONLS), functional disability score, and Berg Balance Scale
      (BBS). Thirty-five age- and gender-matched healthy controls (control group) were
      also included in the study. Student's nonpaired or paired t-test were performed
      to compare data between two independent or related groups, respectively. The
      Pearson test was used to examine the correlations between recorded parameters.
      RESULTS: The mean 9-HPT completion time in the dominant hand of CMT patients was
      significantly slower than that in the healthy controls (29.60 +/- 11.89 s vs.
      19.58 +/- 3.45 s; t = -4.728, P < 0.001). Women with CMT completed the 9-HPT
      significantly faster than men with CMT (dominant hand: 24.74 +/- 7.93 s vs. 33.01
      +/- 13.14 s, t = 2.097, P = 0.044). The gait speed of the average self-selected
      velocity and the average fast-velocity assessed using 10-MWT for CMT patients
      were significantly slower than those in the control group (1.03 +/- 0.18 m/s vs.
      1.44 +/- 0.17 m/s, t = 9.333, P < 0.001; 1.31 +/- 0.30 m/s vs. 1.91 +/- 0.25 m/s,
      t = 8.853, P < 0.001, respectively). There was no difference in gait speed
      between men and women. Both 9-HPT and 10-MWT were significantly correlated with
      the ONLS, functional disability score, and BBS (P < 0.05 for all). CONCLUSION:
      The 9-HPT and 10-MWT might be useful for functional assessment in Chinese
      patients with CMT.

PMID- 28748849
TI  - A Novel Missense Mutation in Peripheral Myelin Protein-22 Causes Charcot-Marie
      Tooth Disease.
AB  - BACKGROUND: Charcot-Marie-Tooth disease (CMT) is the most common inherited
      peripheral neuropathy. A great number of causative genes have been described in
      CMT, and among them, the heterozygous duplication of peripheral myelin protein-22
      (PMP22) is the major cause. Although the missense mutation in PMP22 is rarely
      reported, it has been demonstrated to be associated with CMT. This study
      described a novel missense mutation of PMP22 in a Chinese family with CMT
      phenotype. METHODS: Targeted next-generation sequencing (NGS) was used to screen
      the causative genes in a family featured with an autosomal dominant demyelinating
      form of CMT. The potential variants identified by targeted NGS were verified by
      Sanger sequencing and classified according to the American College of Medical
      Genetics and Genomics standards and guidelines. Further cell transfection studies
      were performed to characterize the function of the novel variant. RESULTS: Using
      targeted NGS, a novel heterozygous missense variant in PMP22 (c.320G>A, p.G107D)
      was identified. In vitro cell functional studies revealed that mutant PMP22
      protein carrying p.G107D mutation lost the ability to reach the plasma membrane,
      was mainly retained in the endoplasmic reticulum, and induced cell apoptosis.
      CONCLUSIONS: This study supported the notion that missense mutations in PMP22
      give rise to a CMT phenotype, possibly through a toxic gain-of-function
      mechanism.

PMID- 28748850
TI  - Correlation between Electroencephalogram Alterations and Frontal Cognitive
      Impairment in Esophageal Cancer Patients Complicated with Depression.
AB  - BACKGROUND: Some esophageal cancer patients complicated with depression exhibit
      cognitive impairments. Frontal electroencephalogram (EEG) may be used as a
      reliable biomarker for prefrontal-mediated cognitive functions. This study was to
      investigate alterations of EEG and frontal cognitive impairment in esophageal
      cancer patients complicated with depression and to assess their correlation.
      METHODS: Sixty-five esophageal cancer patients with depression (study group) and
      62 healthy controls (control group) were included in this study. The study group
      were assigned into psychotic depressed (PD, n = 32) and nonpsychotic depressed
      (NPD, n = 33) subgroups based on complication with psychotic symptoms (Brief
      Psychiatric Rating Scale [BPRS] >35). EEG examination, Beck self-rating
      depression scale, and BPRS were used to assess clinical symptoms. Chi-square
      test, two independent sample t-test, one-way analysis of variance, and Kruskal
      Wallis test were utilized to compare the variables between two groups. EEG
      abnormalities and scores of frontal cognitive function test were analyzed by
      partial correlation analysis in the PD and NPD subgroups. RESULTS: Compared with
      control group, the study group displayed greater scores either in the Stroop test
      (19.89 +/- 2.05 vs. 24.12 +/- 2.19, P = 0.006) or Color Trails Test (CTT; 11.92
      +/- 1.01 vs. 15.02 +/- 1.63, P = 0.008), and reduced score (35.05 +/- 2.01 vs.
      32.11 +/- 2.38, P = 0.007) in the verbal fluency test (VFT). Compared to NPD
      subgroup, PD subgroup exhibited increased scores in Stroop test (22.89 +/- 2.07
      vs. 25.38 +/- 2.32, P = 0.009) and CTT (13.16 +/- 1.71 vs. 15.82 +/- 1.13, P =
      0.008). Moreover, increased scores in Stroop test and CTT as well as scores in
      VFT were associated with the severity of depression. The study group had an
      abnormal frontal EEG, such as alpha forward, alpha asymmetry, alpha moderation,
      and increased theta activity relative to control group. Similarly, compared with
      NPD subgroup, PD subgroup displayed alpha forward, alpha asymmetry, and alpha
      moderation. The correlation test revealed that alpha forward and alpha asymmetry
      were negatively associated with VFT score, but positively correlated with the
      scores of CTT and the Stroop test in PD subgroup. In addition, alpha asymmetry in
      NPD subgroup was positively related to CTT scores. CONCLUSION: This study
      indicated that frontal cognitive impairment in esophageal cancer patients
      complicated with depression is associated with EEG alterations.

PMID- 28748851
TI  - Insights into Initial Demyelinating Episodes of Central Nervous System during
      Puerperium.
AB  - BACKGROUND: Inflammatory demyelinating disease of central nervous system (CNS) is
      an inflammatory disease characterized by a high childbearing female predominance.
      Labor-related alterations for postpartum demyelinating attacks are not entirely
      clear. This study aimed to summarize clinical features of female patients of
      reproductive age with initial CNS inflammatory demyelinating attacks during
      puerperium. METHODS: Fourteen female patients with initial demyelinating events
      during puerperium between January 2013 and December 2016 were retrospectively
      studied. Records of clinical features, neuroimaging, serum antibodies,
      cerebrospinal fluid (CSF) findings, annualized relapse rate (ARR), and treatment
      were analyzed. RESULTS: Among 14 patients, 5 patients were diagnosed with
      multiple sclerosis (MS), four as neuromyelitis optica (NMO), two as longitudinal
      extensive transverse myelitis, two as clinical isolated syndrome (CIS), and one
      as acute brainstem syndrome. All the 14 puerperal female patients presented with
      more than one manifestation of hemiplegia, paraplegia, uroschesis, visual loss or
      dysarthria, and with mild to moderate abnormalities of CSF. Attacks occurred
      during the first trimester postpartum and cesarean section was the main delivery
      way (n = 10). Median Expanded Disability Status Scale (EDSS) scores were 5.0
      (range: 2.0-9.0) at the onset and 2.5 (range: 0-7.0) at the end of follow-ups.
      Patients with MS and CIS had a significantly lower EDSS scores than patients with
      NMO spectrum disorders (P < 0.05). Median ARR was 0.46 (range: 0-1.16); all
      patients had a low ARR (0.49 +/- 0.34, 95% confidence interval: 0.29-0.69) with
      standardized treatments. CONCLUSION: Labor-related alterations in the mother's
      immune system might result in newly-onset demyelinating diseases of central
      nervous system.

PMID- 28748852
TI  - Pretreated Glehnia littoralis Extract Prevents Neuronal Death Following Transient
      Global Cerebral Ischemia through Increases of Superoxide Dismutase 1 and Brain
      derived Neurotrophic Factor Expressions in the Gerbil Hippocampal Cornu Ammonis 1
      Area.
AB  - BACKGROUND: Glehnia littoralis, as a traditional herbal medicine to heal various
      health ailments in East Asia, displays various therapeutic properties including
      antioxidant effects. However, neuroprotective effects of G. littoralis against
      cerebral ischemic insults have not yet been addressed. Therefore, in this study,
      we first examined its neuroprotective effects in the hippocampus using a gerbil
      model of transient global cerebral ischemia (TGCI). METHODS: Gerbils were
      subjected to TGCI for 5 min. G. littoralis extract (GLE; 100 and 200 mg/kg) was
      administrated orally once daily for 7 days before ischemic surgery.
      Neuroprotection was examined by neuronal nuclear antigen immunohistochemistry and
      Fluoro-Jade B histofluorescence staining. Gliosis was observed by
      immunohistochemistry for glial fibrillary acidic protein and ionized calcium
      binding adapter molecule 1. For neuroprotective mechanisms, immunohistochemistry
      for superoxide dismutase (SOD) 1 and brain-derived neurotrophic factor (BDNF) was
      done. RESULTS: Pretreatment with 200 mg/kg of GLE protected pyramidal neurons in
      the cornu ammonis 1 (CA1) area from ischemic insult area (F = 29.770, P < 0.05)
      and significantly inhibited activations of astrocytes (F = 22.959, P < 0.05) and
      microglia (F = 44.135, P < 0.05) in the ischemic CA1 area. In addition,
      pretreatment with GLE significantly increased expressions of SOD1 (F = 28.561, P
      < 0.05) and BDNF (F = 55.298, P < 0.05) in CA1 pyramidal neurons of the sham- and
      ischemia-operated groups. CONCLUSIONS: Our findings indicate that pretreatment
      with GLE can protect neurons from ischemic insults, and we suggest that its
      neuroprotective mechanism may be closely associated with increases of SOD1 and
      BDNF expressions as well as attenuation of glial activation.

PMID- 28748853
TI  - Pingyangmycin Pretreatment Influences the Biological Behavior of Ocular Venous
      Malformation and Relates with Galectin-3 Expression.
AB  - BACKGROUND: Galectin-3 (Gal-3) plays a role in the mechanisms underlying ocular
      venous malformation. We conducted this study to investigate the effect of
      pingyangmycin pretreatment on the Gal-3 expressions and biological behavior of
      ocular venous malformation. METHODS: Tissue samples were collected from 136
      patients with ocular venous malformation. Patients were randomly divided into
      pingyangmycin (n = 69) and nonpingyangmycin group (n = 67). Patients in the
      pingyangmycin group received a local injection of 0.02% pingyangmycin once every
      2 days for 2 weeks (7 doses) before removal surgery, whereas patients in the
      nonpingyangmycin group underwent removal surgery without local injection. The
      protein and messenger RNA (mRNA) expression of Gal-3 were detected by using
      immunohistochemistry and in situ hybridization. RESULTS: Gal-3 protein was
      expressed in 35 (52%) of 67 samples in the nonpingyangmycin group and in 19 (28%)
      of 69 samples in the pingyangmycin group (P < 0.05). Gal-3 mRNA expression was
      detected in 39 (58%) of 67 samples in the nonpingyangmycin group and 22 (32%) of
      69 samples in the pingyangmycin group (P < 0.05). The higher Gal-3 expressions
      were detected in samples with deeper invasiveness than those with superficial
      invasiveness before (chi2 = 12.720 and 13.369, respectively, both P < 0.05) and
      after pingyangmycin treatment (chi2 = 8.429 and 4.590, respectively, both P <
      0.05). It was more frequently detected in mesh-like lesions with unclear boundary
      than round lesions with clear boundary before (chi2 = 30.291 and 41.466,
      respectively, both P < 0.05) and after pingyangmycin treatment (chi2 = 14.619 and
      15.130, respectively, both P < 0.05). Pingyangmycin treatment led to a
      significant difference in Gal-3 expressions at both protein and mRNA levels (chi2
      = 8.664 and 9.524, respectively, both P < 0.05). CONCLUSIONS: Gal-3 expression
      may be involved in the development and invasiveness of ocular venous
      malformation, and pingyangmycin can inhibit Gal-3 expression, indicating a role
      of pingyangmycin treatment before the removal of ocular venous malformation.

PMID- 28748854
TI  - Ratios of T-helper 2 Cells to T-helper 1 Cells and Cytokine Levels in Patients
      with Hepatitis B.
AB  - BACKGROUND: Hepatitis B is an immune response-mediated disease. The aim of this
      study was to explore the differences of ratios of T-helper (Th) 2 cells to Th1
      cells and cytokine levels in acute hepatitis B (AHB) patients and chronic
      hepatitis B virus (HBV)-infected patients in immune-tolerance and immune-active
      phases. METHODS: Thirty chronic HBV-infected patients in the immune-tolerant
      phase (IT group) and 50 chronic hepatitis B patients in the immune-active
      (clearance) phase (IC group), 32 AHB patients (AHB group), and 13 healthy
      individuals (HI group) were enrolled in the study. Th cell proportions in
      peripheral blood, cytokine levels in plasma, and serum levels of HBV DNA,
      hepatitis B surface antigen, and hepatitis B e antigen were detected. RESULTS:
      The Th1 cell percentage and Th2/Th1 ratio in the HBV infection group (including
      IT, IC, and AHB groups) were significantly different from those in HI group
      (24.10% +/- 8.66% and 1.72 +/- 0.61 vs. 15.16% +/- 4.34% and 2.40 +/- 0.74,
      respectively; all P < 0.001). However, there were no differences in the Th1 cell
      percentages and Th2/Th1 ratios among the IT, IC, and AHB groups. In HBV infection
      group, the median levels of Flt3 ligand (Flt3L), interferon (IFN)-gamma, and
      interleukin (IL)-17A were significantly lower than those in HI group (29.26
      pg/ml, 33.72 pg/ml, and 12.27 pg/ml vs. 108.54 pg/ml, 66.48 pg/ml, and 35.96
      pg/ml, respectively; all P < 0.05). IFN-alpha2, IL-10, and transforming growth
      factor (TGF)-beta2 median levels in hepatitis group (including patients in AHB
      and IC groups) were significantly higher than those in IT group (40.14 pg/ml,
      13.58 pg/ml, and 557.41 pg/ml vs. 16.74 pg/ml, 6.80 pg/ml, and 419.01 pg/ml,
      respectively; all P < 0.05), while patients in hepatitis group had significant
      lower Flt3L level than IT patients (30.77 vs. 59.96 pg/ml, P = 0.021). Compared
      with IC group, patients in AHB group had significant higher median levels of IL
      10, TGF-beta1, and TGF-beta2 (22.77 pg/ml, 10,447.00 pg/ml, and 782.28 pg/ml vs.
      8.66 pg/ml, 3755.50 pg/ml, and 482.87 pg/ml, respectively; all P < 0.05).
      CONCLUSIONS: Compared with chronic HBV-infected patients in immune-tolerance
      phase, chronic HBV-infected patients in immune-active phase and AHB patients had
      similar Th2/Th1 ratios, significantly higher levels of IFN-alpha2, IL-10, and TGF
      beta. AHB patients had significantly higher IL-10 and TGF-beta levels than
      chronic HBV-infected patients in immune-active phase.

PMID- 28748855
TI  - Clinical Characteristics and Endoscopic Endonasal Removal of Foreign Bodies
      within Sinuses, Orbit, and Skull Base.
AB  - BACKGROUND: Foreign bodies within the sinuses, orbit, and skull base (FBSOS) are
      rare; hence, diagnosis and management guidelines are lacking. Endoscopic sinus
      surgery (ESS) removal is preferred because of the less invasiveness and minimal
      morbidity. This study was designed to summarize clinical experience with ESS
      management of FBSOS. METHODS: We retrospectively reviewed clinical
      manifestations, imaging findings, treatment, and outcomes in consecutive patients
      with ESS removal of FBSOS between 2004 and 2015 at a tertiary academic medical
      center. The Chi-square test was performed to compare the infection rate between
      wooden and nonwooden FBSOS. RESULTS: There were 23 male and five female patients,
      with median age of 11 years. FBSOS were located within the sinuses (86%), orbit
      (75%), and skull base/intracranial region (46%). Wooden FBSOS had a significantly
      higher risk of infection (78%) compared with nonwooden FBSOS (5%, P < 0.05).
      Contrast-enhanced computed tomography (CT) plus three-dimensional reconstruction
      was sensitive in all cases. Twenty-seven (96%) FBSOS were removed by ESS alone,
      while 1 (4%) FBSOS was removed using the combined ESS and lateral cervical
      approach. Four of the nine intracranial penetrating FBSOS patients had
      intraoperative cerebrospinal fluid (CSF) leak and received endoscopic CSF leak
      repair. Twelve (43%) patients suffered complications (meningitis, diplopia, and
      vision loss). CONCLUSIONS: ESS is a minimally invasive, safe, and promising
      surgical approach for FBSOS removal. Contrast-enhanced CT is effective in
      preoperative diagnosis and intraoperative guidance. Wooden FBSOS had higher risk
      of infection, thus antibiotics are recommended.

PMID- 28748856
TI  - The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative
      Tumor Suppressor.
AB  - BACKGROUND: Nuclear mitotic apparatus protein 1 (NuMA1) had been reported to
      produce three groups of isoforms categorized as long, middle, and short groups,
      of which short NuMA displayed distinct localization patterns compared to long and
      middle isoforms. However, the function of short NuMA was not clear in the
      progress of cancer formation. This study aimed to unveil the role of short NuMA
      in cancer pathogenesis. METHODS: The expression levels of short isoforms were
      explored in paired gastric carcinoma (GC) samples and different cell lines.
      Furthermore, the short isoform behaved as a putative tumor suppressor based on
      cell proliferation and cell colony formation assays. Pull-down assay and whole
      genome gene expression analysis were carried out to search candidate interaction
      partners of short NuMA. RESULTS: The expression of short NuMA was highly
      expressed in S and G2 phases of the cell cycle; compared with nontumor tissues,
      short NuMA downregulated in nine GCs (GC1 [0.131, P = 5 * 10-4]; GC2 [0.316, P =
      3 * 10-5]; GC3 [0.111, P = 6 * 10-4]; GC4 [0.456, P = 0.011]; GC5 [0.474, P =
      0.001]; GC6 [0.311, P = 0.004]; GC7 [0.28, P = 3 * 10-5]; GC8 [0.298, P = 0.007];
      and GC9 [0.344, P = 0.002]). Besides, high expression of short NuMA significantly
      inhibits cell growth (2.43 * 105 vs. 2.97 * 105, P = 0.0029) and cell clone
      information in vitro (70 vs. 2, P = 1.67 * 10-45). Short NuMA could bind with
      alpha-actinin-4 (ACTN4), a putative tumor promoting gene. Overexpression of short
      NuMA could tremendously decrease the expression of MYB proto-oncogene like 2
      (MYBL2) of about 92-fold, which played an important role in the cell cycles.
      CONCLUSIONS: Short isoform of NuMA might be functioned as a putative role of
      tumor suppressor. Further studies should be made to illuminate the relationship
      between ACTN4, MYBL2, and tumor progression.

PMID- 28748857
TI  - Effect of High-fat Diet-induced Disorders on Rat with Endometrial Hyperplasia and
      Adiponectin System in Circulation and Uterus.
AB  - BACKGROUND: Epidemiologic and genetic studies suggest a link between insulin
      resistance (IR) and endometrial cancer, and endometrial hyperplasia (EH) is a
      precancerous stage of endometrial cancer. Adiponectin is an adipokine which
      previously shown to be a risk factor for endometrial cancer. The aim of the study
      was to develop a rat model of IR and EH and evaluate adiponectin system in
      circulation and uterus. METHODS: This study was a 46-week animal trial from
      February 2014 to January 2015. Female Sprague-Dawley rats were fed with high-fat
      diet (HFD) for 40 weeks to induce IR. Followed by ovariectomization, rats were
      orally administrated to 17beta-estradiol (E2) for 4 weeks to induce EH and then
      sacrificed. A total of 36 rats were divided into four groups: E2, HFD, HFD + E2,
      and control groups. Data were analyzed with Student's t-test, one-way analysis of
      variance (ANOVA), and Mann-Whitney U-tests. Chi-square was used to evaluate the
      score of immunohistochemistry. RESULTS: The thickness of endometrial, glandular
      epithelium, and myometrium in the HFD-E2group were higher than the E2group (F =
      59.02, F = 23.51 and F = 12.53, respectively, all P < 0.001). Plasma adiponectin
      levels in the E2group were lower than those in the control group, and the levels
      in the HFD-E2group were lower than those in the HFD group (F = 13.15, P < 0.05).
      However, after normalized to visceral adipose tissue, compared to the control
      group, plasma adiponectin levels were decreased in rat with HFD in the absence or
      presence of E2, respectively (F = 6.72, P < 0.05). Adiponectin gene (F = 10.48, P
      < 0.05) and protein (P < 0.05) levels in uterus in the HFD-E2group were higher
      than those in the HFD group. CONCLUSIONS: This study manifests that IR can
      effectively modulate EH, which suggests the involvement of energetic metabolism
      in uterine alternation. The combination effects of IR and EH modulate circulating
      adiponectin levels. However, adiponectin gene and protein levels in uterus are
      mainly response to estradiol.

PMID- 28748858
TI  - Chinese Guidelines for the Diagnosis and Management of Tumefactive Demyelinating
      Lesions of Central Nervous System.

PMID- 28748859
TI  - Recommendations for Electroencephalography Monitoring in Neurocritical Care
      Units.

PMID- 28748861
TI  - Current Evidences for the Use of UEscope in Airway Management.
AB  - OBJECTIVE: UEscope is a new angulated videolaryngoscope (VL). This review aimed
      to describe the features of UEscope and provide clinical evidences regarding the
      efficacy and safety of this video device in adult tracheal intubation and its
      roles in airway management teaching. DATA SOURCES: The Wan Fang Data, CNKI,
      PubMed, Embase, Cochrane Library, and Google Scholar were searched for relevant
      English and Chinese articles published up to January 15, 2017, using the
      following keywords: "HC video laryngoscope", "UE videolaryngoscope", "video
      laryngoscope", and "videolaryngoscopy". STUDY SELECTION: Human case reports, case
      series, observable studies, and randomized controlled clinical trials were
      included in our search. The results of these studies and their reference lists
      were cross-referenced to identify a common theme. RESULTS: UEscope features the
      low-profile portable design, intermediate blade curvatures, all-angle adjustable
      monitor, effective anti-fog mechanisms, and built-in video recording function.
      During the past 5 years, there have been a number of clinical studies assessing
      the application and roles of UEscope in airway management and education. As
      compared with direct laryngoscope, UEscope improves laryngeal visualization,
      decreases intubation time (IT), and increases intubation success rate in adult
      patients with normal and difficult airways. These findings are somewhat different
      from the previous results regarding the other angulated VLs; they can provide an
      improved laryngeal view, but no conclusive benefits with regard to IT and
      intubation success rate. Furthermore, UEscope has extensively been used for
      intubation teaching and shown a number of advantages. CONCLUSIONS: UEscope can be
      used as a primary intubation tool and may provide more benefits than other VLs in
      patients with normal and difficult airways. However, more studies with large
      sample are still needed to address some open questions about clinical performance
      of this new VL.

PMID- 28748862
TI  - Imaging Features of Symptomatic Radiation-induced Cervical Artery Stenosis.

PMID- 28748860
TI  - Current Nondopaminergic Therapeutic Options for Motor Symptoms of Parkinson's
      Disease.
AB  - OBJECTIVE: The aim of this study was to summarize recent studies on
      nondopaminergic options for the treatment of motor symptoms in Parkinson's
      disease (PD). DATA SOURCES: Papers in English published in PubMed, Cochrane, and
      Ovid Nursing databases between January 1988 and November 2016 were searched using
      the following keywords: PD, nondopaminergic therapy, adenosine, glutamatergic,
      adrenergic, serotoninergic, histaminic, and iron chelator. We also reviewed the
      ongoing clinical trials in the website of clinicaltrials.gov. STUDY SELECTION:
      Articles related to the nondopaminergic treatment of motor symptoms in PD were
      selected for this review. RESULTS: PD is conventionally treated with dopamine
      replacement strategies, which are effective in the early stages of PD. Long-term
      use of levodopa could result in motor complications. Recent studies revealed that
      nondopaminergic systems such as adenosine, glutamatergic, adrenergic,
      serotoninergic, histaminic, and iron chelator pathways could include potential
      therapeutic targets for motor symptoms, including motor fluctuations, levodopa
      induced dyskinesia, and gait disorders. Some nondopaminergic drugs, such as
      istradefylline and amantadine, are currently used clinically, while most such
      drugs are in preclinical testing stages. Transitioning of these agents into
      clinically beneficial strategies requires reliable evaluation since several
      agents have failed to show consistent results despite positive findings at the
      preclinical level. CONCLUSIONS: Targeting nondopaminergic transmission could
      improve some motor symptoms in PD, especially the discomfort of dyskinesia.
      Although nondopaminergic treatments show great potential in PD treatment as an
      adjunct therapy to levodopa, further investigation is required to ensure their
      success.

PMID- 28748863
TI  - In vitro Stent Graft Fenestration to Preserve All Supra-aortic Branches in the
      Treatment of a Stanford Type A Aortic Arch Dissection.

PMID- 28748864
TI  - An Improved Urethral Catheterization in Female Pigs: A Pilot Study.

PMID- 28748865
TI  - Dysgerminoma and Gonadoblastoma with Para-aortic Lymph Node Metastasis in a
      Patient with Swyer Syndrome.

PMID- 28748866
TI  - Intraorbital Electroacupuncture Therapy for Thyroid-associated Ophthalmopathy.

PMID- 28748867
TI  - Is the Future of Health-care Technology or Goal Driven?

PMID- 28748868
TI  - Elephantiasic Pretibial Myxedema with Involvement of the Buttocks and Face.

PMID- 28748869
TI  - Vigilance in Prescribing Nonsteroidal Anti-inflammatory Drugs.

PMID- 28748870
TI  - Reply to Vigilance in Prescribing Nonsteroidal Anti-inflammatory Drugs.

PMID- 28748871
TI  - Toxicity of star fruit (Averrhoa carambola) in renal patients: A systematic
      review of the literature.
AB  - Several reports have discussed the neurotoxic effects of star fruit (Averrhoa
      carambola) in patients with chronic kidney disease (CKD). There is also some
      evidence highlighting the potentially harmful effects on patients with apparently
      normal renal function, who after consuming this fruit, developed acute renal
      injury. We performed a systematic review of the literature in the two main global
      databases (PubMed and Embase) as well as in Lilacs, for Latin American
      publications. We also included case reports, case series, or review articles
      which presented individual patient data. Animal or in vitro studies were
      excluded. We initially screened 259 references, of which 42 were selected for
      full-text review and 26 were finally selected for data extraction. A total of 123
      patients from eight countries were documented: Brazil, with 47 cases, had the
      highest reported incidence, followed by Taiwan (36), Bangladesh (20), China and
      France (8 each), Sri Lanka (2), and Thailand and Colombia (1 each); 28 (22%) of
      the patients died. Despite the relatively low frequency of star fruit
      consumption, it has become a global issue. Patients with already diagnosed CKD
      are the obvious target for preventive measures, but persons with undiagnosed
      kidney conditions could also be at risk.

PMID- 28748872
TI  - Assessment of frailty in elderly pre-dialysis population using simple tools.
AB  - Prevalence of chronic kidney disease (CKD) is increasing worldwide principally
      among the elderly population many of whom will eventually need renal replacement
      therapy. The relationship between frailty and CKD in the elderly population has
      been recognized. However, studies concentrating on frailty in pre-dialysis
      patients are limited. CKD predisposes to frailty through many potential
      mechanisms; anemia, bone mineral disease, oxidative stress, and malnutrition
      which in turn lead to progression of CKD culminating in a vicious cycle.
      Identifying potential causes of frailty in elderly pre-dialysis patients and
      recognizing individuals at risk should be an area of focus to nephrologists and
      researchers. Modalities that may improve frailty in elderly pre-dialysis patients
      such as treatment of anemia and bone mineral disease may improve outcome.
      However, this has not been established and further research is needed. The aim of
      this review is to address the importance of recognizing frailty in elderly pre
      dialysis patients using simple tools and describing its implications on clinical
      outcome.

PMID- 28748873
TI  - Apoptosis of rat renal cells by organophosphate pesticide, quinalphos:
      Ultrastructural study.
AB  - Quinalphos or Ekalux, an organophosphate pesticide, is used in controlling the
      pests of a variety of crops. Quinalphos was studied on male Sprague-Dawley albino
      rats. The acute po LD50 of technical Ekalux was 19.95 mg/kg in males. Ekalux,
      produced several pathological changes in the kidney. A glomerulus demonstrated
      capillary lumina occluded by degenerated cellular debris. Basement membrane
      showed irregular wrinkling and branching. The proximal tubular cells showed
      damage such as dilation of endoplasmic reticulum, accumulation of glycogen
      granules, and pyknotic nucleus. The changes also included swelling of the
      mitochondria and reduction of the cristae up to total destruction. The distal
      tubular changes included electron lucency and vacuolation of cytoplasm. The
      distal convoluted tubule wall showed edematous epithelial cells, formation of
      blebs, and microvilli loss. These results suggest that subchronic exposure of
      rats to Ekalux causes ultrastructural changes in renal corpuscle and marked
      ultrastructural changes in proximal and distal tubules.

PMID- 28748874
TI  - Variables affecting darbepoetin resistance index in hemodialysis patients.
AB  - Erythropoietin resistance index calculation has been used as a tool to evaluate
      anemia response to erythropoietin therapy. Very little has been reported in its
      use when using darbepoetin and factors influencing in Arab patients. Darbepoetin
      resistance index (DRI) was calculated in all our patients using darbepoetin. This
      was correlated to demographic, clinical, and laboratory parameters. Of the 250
      patients, 40.4% were diabetic, 71.1% on hemodialysis, and 28.6% on
      hemodiafiltration), 23.9% with PermCaths (PC), and 76.1 % with arteriovenous
      fistula (AVF). The mean DRI was 10.96 +/- 12.9 I. Females had 45% higher DRI than
      males (P = 0.005), and patients with PC had a 66% higher DRI than those with AVF
      (P = 0.029). Patients with Vitamin D level below the 50th percentile had 55.9%
      higher DRI than those above it (P = 0.05). DRI was negatively correlated with age
      (P = 0.018), dialysis vintage (P = 0.039), interdialytic weight gain P = 0.007),
      Vitamin D level, and serum albumin (P = 0.005) and positively correlate with
      parathyroid hormone (PTH) level (P = 0.000). No impact was seen by the mode of
      dialysis, being diabetic, using anti-hypertensive therapy, body mass index, Kt/V,
      serum iron, total iron binding capacity, transferrin saturation, ferritin, C
      reactive protein, Ca, or P. DRI in our Arab patients was comparable to
      erythropoietin resistance indices reported in other communities. Higher DRI was
      observed in females, PC users, lower serum albumin, lower Vitamin D, and shorter
      dialysis vintage. A negative correlation existed between DRI and age, dialysis
      vintage, interdialytic weight, and serum albumin and a positive correlation with
      PTH level.

PMID- 28748875
TI  - A comparative study to evaluate factors that influence survival in
      multidisciplinary predialysis educated patients and "Crashlanders".
AB  - Integrated multidisciplinary predialysis education (MPE) is usually provided to
      support and prepare the pre-end-stage renal disease (ESRD) patients before the
      initiation of renal replacement therapy (RRT). However, the impact of MPE is not
      known in our population, which is comprised patients of Asian origins and
      recipients of a totally subsidized health-care system. This research compared the
      survival probability, sociodemographic, and clinical characteristics of MPE
      patients and non-MPE patients (or crashlanders). A retrospective cohort study was
      conducted to investigate ESRD patients who started RRT in Brunei Darussalam from
      January 2013 to December 2014. Data were extracted from the computerized clinical
      database and dialysis records. A total of 351 new cases of ESRD patients who
      started on hemodialysis during the study period were included in the study. The
      median age was 56.0 years, with a slight male preponderance (56.6%). The MPE
      group was significantly older (P = 0.001) and more likely to have a history of
      diabetes mellitus (P = 0.013), ischemic heart disease (P = 0.014), and
      hypertension (P = 0.016). Despite being older and having more comorbidities (P =
      0.028), MPE patients have a better survival probability (P = 0.028) and a 34%
      decreased risk of dying. Of those who died, older age (P = 0.001), higher serum
      creatinine (P = 0.01), and lower hemoglobin level (P = 0.017) were significant
      prognostic indicators. MPE before the initiation of RRT contributed to greater
      survival probability in near ESRD patients. The survival benefits were evident
      despite the presence of inherent risks (older age and presence of comorbidities)
      in the MPE population in comparison with the non-MPE cohort.

PMID- 28748876
TI  - End-stage renal disease in patients with sickle cell disease.
AB  - Sickle cell nephropathy is a severe complication of sickle cell disease (SCD)
      that has a wide range of manifestations, from asymptomatic microalbuminuria to
      end-stage renal disease (ESRD). The data on patients with SCD who develop ESRD
      are scarce. The aim of this study was to explore the course of patients with SCD
      who developed ESRD and received renal replacement therapy (RRT). The course of
      patients with SCD who developed ESRD and started dialysis at two centers in the
      Eastern Province of Saudi Arabia was retrospectively analyzed. Parameters
      included age at initiation of dialysis, survival until death or kidney
      transplantation, hospitalization due to pain crisis, disease-related parameters,
      and requirement for blood transfusion. Sixteen patients with SCD developed ESRD
      and started RRT with either hemodialysis or peritoneal dialysis. The mean age at
      initiation of dialysis was 46.6 years. The majority of patients (10 out of 16)
      were resistant to erythropoiesis-stimulating agents (ESA) and required blood
      transfusion repeatedly. Pain crises were infrequently encountered. Median
      survival was 54 months. Four patients received kidney transplantation with good
      outcome. In conclusion, most patients with SCD who developed ESRD were resistant
      to ESA and required repeated blood transfusion. The rate of hospitalization due
      to pain crisis was relatively low. Survival on dialysis was comparable to that of
      patients with no SCD, and the post-transplant course was relatively benign.

PMID- 28748877
TI  - Vitamin D levels and other biochemical parameters of mineral bone disorders and
      their association with diastolic dysfunction and left ventricular mass in young
      nondiabetic adult patients with chronic kidney disease.
AB  - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in
      patients with end-stage renal disease. Chronic kidney disease (CKD)-associated
      cardiovascular mortality is more prevalent in those with diastolic heart failure
      and is an early predictor, while increased left ventricular mass (LVM) is a
      strong independent risk factor. Hypovitaminosis D is extensively being studied as
      a nontraditional risk factor for CVD. The aim of the present study is to look at
      the association of Vitamin D and other parameters of mineral bone disorder (MBD)
      with diastolic dysfunction and LVM in nondiabetic young adult patients with CKD.
      This was a hospital-based, cross-sectional observational study. Groups I and II
      comprised nondiabetic predialysis CKD patients (stage 4 and 5) and healthy
      controls, respectively. Groups IA and IB comprised cases with and without
      diastolic dysfunction, respectively. Vitamin D level was measured by enhanced
      chemiluminescence method and intact parathyroid hormone (iPTH) by
      electrochemiluminescence method. Parameters for diastolic function and LVM were
      assessed by Doppler echocardiography, tissue Doppler imaging, and M-mode
      echocardiography. Vitamin D level was significantly lower in Group I as compared
      to Group II. Diastolic dysfunction was present in 48.8% of the cases and was
      significantly associated with serum phosphorus and calcium-phosphorous product,
      but not with Vitamin D level. A statistically significant positive correlation
      between LVM and iPTH was found in our study. Hyperphosphatemia and high calcium
      phosphorous product can be a better early predictor of diastolic dysfunction than
      Vitamin D while secondary hyperpara-thyroidism with increased LVM may be a bad
      prognostic marker.

PMID- 28748878
TI  - Assessment of hepatic fibrosis by fibroscan in egyptian chronic hemodialysis
      patients with chronic Hepatitis C (genotype 4): A single-center study.
AB  - Assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C
      (CHC) can help to evaluate the long-term prognosis, complications of hepatitis C
      virus (HCV) as well as eligibility for renal transplantation,. Our aim was to
      assess liver fibrosis in Egyptian hemodialysis (HD) patients infected with CHC
      genotype 4 using a fibroscan. This cross-sectional observational study was
      conducted over two years on a cohort of 134 Egyptian patients on prevalent HD at
      Kasr Al Ainy Hospital. All patients were subjected to routine laboratory
      evaluation including, hepatitis B surface antigen, hepatitis B core antibody,
      hepatitis Be antigen, hepatitis C antibody (HCVAb) and human immunodeficiency
      virus antibody, quantitative polymerase chain reaction (PCR) for both HCV and
      hepatitis B virus (HBV), serum hyaluronic acid level, and alpha-fetoprotein
      (AFP). Fibroscan was performed on all HCV-positive patients. The mean age was
      47.43 +/- 12.65 years, 50.7% were male, and 49.3% were female. The most common
      causes of end-stage renal disease were hypertensive nephropathy (32.1%) and
      diabetic nephropathy (18.7%). HCVAb was positive in 57.5% of the patients and HBV
      was positive in 3%. Forty HCV-positive patients (57.1%) who underwent fibroscan
      had mild to significant fibrosis, and thirty patients (42.9%) had advanced
      fibrosis. There was significant correlation between HCV PCR and duration on HD,
      number of blood transfusions, and hyaluronic acid (HA) level. In addition, there
      was a significant correlation between serum HA and HD duration as well as liver
      fibrosis. No significant correlation was found between duration on HD and
      fibrosis stage (P = 0.619); also, no significant correlation was noted between
      the age of the patients and HA level or stage of fibrosis (P = 0.970). Fibro-scan
      is a simple noninvasive test that can be used to assess liver fibrosis in HD
      patients with CHC. Most of the study patients had mild to significant fibrosis.

PMID- 28748879
TI  - Early clinical manifestations and laboratory findings before and after treatment
      of cytomegalovirus infection in kidney transplant patients.
AB  - Cytomegalovirus (CMV) is one of the most frequently encountered opportunistic
      viral pathogens in kidney transplant recipients. In this study, we
      retrospectively reviewed all living related and unrelated kidney transplant
      recipients on regular follow-up from January 2006 to June 2015, who were
      suspected to have CMV clinically and confirmed by DNA polymerase chain reaction
      (PCR). CMV PCR was detected in 102 kidney transplant recipients. The median time
      of detection after kidney transplant was 21 months, ranging from 15 days to 84
      months. There were 58 male and 44 female patients. The induction
      immunosuppression in living related kidney transplants was with antithymocyte
      globulin or basiliximab, whereas the most common maintenance immunosuppressive
      regimen was with cyclosporine, mycophenolate mofetil, and prednisolone. Most of
      the transplant recipients were asymptomatic at the time of detection of CMV PCR
      (67%). Fever, mainly low grade, was the main presentation in 16% of patients,
      followed by diarrhea (15%) and pneumonitis (2%). The most common hematological
      abnormality was lymphopenia seen in 46% of patients, followed by anemia (40%) and
      thrombocytopenia (14%). The common biochemical abnormalities found were elevated
      alanine aminotransaminase (18%) and hyperbilirubinemia (9%). The serum creatinine
      was found to be above baseline in 72% of patients. All patients with CMV
      infection were treated with intravenous ganciclovir, 2.5-5 mg/kg q 12 hourly,
      according to creatinine clearance, for 21 days. The treatment was successful in
      all but two patients, who died during the treatment period. There was a
      significant improvement in the kidney and liver functions after successful
      treatment of CMV infection. Our study shows that CMV infection should be
      considered in a patient presenting with unexplained rise in serum creatinine, low
      grade fever, diarrhea, or anemia. A significant improvement in kidney and liver
      functions was observed after successful treatment of the infection.

PMID- 28748880
TI  - Incident elderly patients on peritoneal dialysis: Epidemiological characteristics
      and modality impact on survival time.
AB  - Aging of the population and the increased prevalence of diseases such as diabetes
      and arterial hypertension result in an increasing need of dialysis treatment.
      Herein we describe a cohort of elderly patients on peritoneal dialysis (PD) and
      assess the influence of the modality on the long-term survival. Out of a
      multicenter prospective cohort of 2,144 BRAZPD PD incident patients during a
      period from December 2004 to October 2007, 762 elderly adults, defined as
      patients >=65-year-old, were eligible for the study, 413 started on automated PD
      (APD) and 349 on continuous ambulatory PD (CAPD). Patients were followed until
      death, transfer to hemodialysis, recovery of renal function, loss to follow-up,
      or transplantation. Demographics and clinical data were evaluated at baseline and
      described as mean +/- standard deviation, median, or percentage. Competing risk
      and time-dependent Cox analysis were performed, having dialysis modality APD] vs.
      CAPD as a dependent variable, as hazard ratio (HR) is not proportional throughout
      the therapy time. Mean age was 74.5 +/- 6.8 years in APD, 74.6 +/- 6.7 in CAPD,
      50.8% females in APD, 54.4% in CAPD. The frequently observed comorbidities were
      diabetes (52.3% in APD and 47% in CAPD) and left ventricular hypertrophy (36.3%
      in APD and 46.1% in CAPD) whereas 93.6% presented Davies score >=2. In Cox time
      dependent analysis, HR did not show difference up to 18 months HR = 1.11,
      confidence interval (CI) = 0.85-1.46], but thereafter, APD modality revealed
      lower risk of mortality (HR = 0.25, CI = 0.0073-0.86), when compared with CAPD.
      After adjustment for the confounding factors, CAPD presented a higher risk of
      mortality (HR = 4.50, CI = 1.29-15.64). No differences in survival were observed
      up to 18 months of therapy; however, beyond 18 months, APD modality was a
      protection factor.

PMID- 28748881
TI  - Predictive factors of mortality in a tunisian cohort with systemic lupus
      erythematosus.
AB  - Mortality in systemic lupus erythematosus (SLE) has decreased with the advent of
      immunosuppressive therapy and the development of hemodialysis. This study aims to
      evaluate the survival rate, factors of poor prognosis, and causes of death in SLE
      in a Tunisian series. The records of all SLE patients followed up in a single
      center during 1974-2014 were reviewed. The causes of death were identified.
      Prognostic factors of survival were analyzed by multivariate analysis using the
      comparison of the survival rates by the log-rank test. Two hundred ninety-nine
      patients with SLE were included (274 women, 25 men) aged meanly of 27.52 years at
      diagnosis. The death occurred in 50 cases (16.7%). The mean age at death was
      28.46 years (14-69 years). The patient survival rates at 5, 10, and 20 years were
      83.8%, 78.6%, and 56.7%, respectively. The leading causes of death were active
      SLE (50%) and infectious complications (36%). Independent factors of poor
      prognosis identified by multivariate analysis were myocarditis (P = 0.029),
      splenomegaly (P = 0.0015), and worsening of renal function (P = 0.004). Remission
      was identified as a protective factor (P = 0.047). Our study shows that renal
      disease remains the primary cause and the main predictor of death in SLE, which
      is consistent with the literature data.

PMID- 28748882
TI  - Superiority of peginterferon alpha-2a and ribavirin combination over
      peginterferon alpha-2a monotherapy in the management of hemodialysis patients
      with chronic Hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) is a common infection affecting 15% of hemodialysis
      population in Saudi Arabia resulting in delay in transplantation and long-term
      complications. The use of peginterferon resulted in sustained virologic response
      (SVR) in 40%-85% of patients, especially if combined with ribavirin. The
      treatment is hampered by the high dropout due to anemia and requirement of blood
      transfusion resulting from this therapy. Some studies have shown that the
      addition of increasing dose of erythropoiesis-stimulating agents (ESA) and
      reduced dose of ribavirin results in reduced dropout rate with high SVR. We
      conducted an open-label prospective study using either peginterferon alpha-2a
      alone (Group I, 32 patients) or peginterferon alpha-2a plus adjusted dose
      ribavirin (Group II, 26 patients). A total of seven patients dropped from the
      study (2 in Group I and 5 in Group II). Analysis was done only on patients who
      completed the study (thirty patients in Group I and 21 in Group II). There was no
      significant difference in the demographic data, HCV genotype, liver biopsy grade
      and stage, and laboratory tests between the two groups. Patients received ESA to
      combat expected anemia. Group II had a better early virologic response than Group
      I [17 out of 21 (80%) and 14 out of 30 (47%) respectively, P = 0.014] and better
      SVR [18 out of 21 (85%) and 15 out of 30 (50%) respectively, P = 0.009]. There
      were no differences in mean white blood cells, hemoglobin, and platelets between
      the two groups at any time with only four patients dropping out due to anemia or
      side effect of medications. Alanine aminotransferase was lower in both treatment
      groups compared to baseline with no difference between the groups. Peginterferon
      alpha-2a and ribavirin are superior to peginterferon alpha-2a alone in treating
      hemodialysis patients with chronic HCV infection.

PMID- 28748883
TI  - Epidemiology and outcome of tuberculosis in immunocompromised patients.
AB  - The United States Renal Data System showed 1.2% and 1.6% incidences of
      tuberculosis (TB) in patients on peritoneal dialysis and hemodialysis (HD),
      respectively. Kidney transplant (KTX) patients have higher rates. We studied the
      epidemiology and outcome of TB in patients with kidney dysfunction in a tertiary
      care hospital in the past decade. We examined data of patients with TB with and
      without kidney dysfunction from 2006 to 2015 through an electronic system.
      Statistical analysis was completed using Stata software, Chicago, IL, USA. We
      found 581 patients with active TB of whom 37 had renal dysfunction including
      chronic kidney disease, HD, and KTX. No difference was found in the prevalence,
      age, or gender predilection. The age ranged from 1 to 95 with a mean (standard
      deviation) of 38.6 (21.1) years. The incidence of TB is 3 per 100,000. The number
      of patients per year with active TB ranges from 52 to 128 and 3 to 4 in the
      general population and kidney dysfunction group, respectively. Sixty-five percent
      of patients with kidney dysfunction had pulmonary TB, 5% had pleurisy, and 30%
      had extrapulmonary TB. Eighty-four percent of patients with kidney dysfunction
      completed the course of treatment with 16% treatment failure and 0.4% developed
      multidrug-resistant TB; 8% were lost to follow-up and 8% died during the
      treatment period. This study showed no gender predilection for TB in the general
      population and immunocompromised. Duration of symptoms before diagnosis of TB was
      shorter in kidney dysfunction patients in comparison to the general population.
      TB cultures were the most positive tests whereas bronchoalveolar lavage and skin
      test were the least positive for detecting TB in the kidney dysfunction group.
      Improvement in registries and screening is required to enhance the capturing rate
      and detection among this group, as well as providing accurate data to health
      authorities and the public about the magnitude, future trends, treatments, and
      outcomes regarding TB in kidney dysfunction.

PMID- 28748884
TI  - Association between age and cardiovascular status by echosonography in
      asymptomatic predialysis patients with chronic kidney disease.
AB  - Age is an important risk factor for cardiovascular disease in the general
      population and in dialysis patients. The aim of this study is to investigate the
      influence of age on the cardiovascular status of asymptomatic predialysis
      patients with chronic kidney disease (CKD). Echocardiography and carotid
      ultrasound were performed in 61 patients with CKD stages 4-5, who were divided by
      age into two groups: group 1 (>=65 years, n = 31) and group 2 (<65 years, n =
      30). Data were compared with those of control group (>=65 years, n = 20). Group 1
      patients had significantly higher left ventricular mass index (LVMI), (P <0.001),
      worse LV diastolic function (lower E/A ratio: P<0.05, E' velocities: P< 0.001,
      E'/A' ratio: P <0.001, and a higher ratio E/E': P <0.05) and a higher prevalence
      of aortic (P <0.01) and mitral calcification (P <0.001) compared to group 2
      patients. Elderly patients also had significantly increased intima-media
      thickness (IMT, P <0.001) and a greater prevalence of carotid plaques (P <0.05)
      and calcifications (P <0.001) than younger patients. Multiple regression analysis
      showed that IMT, LVMI, and E/A ratio were independent variables associated with
      aging (R2 = 0.605). We concluded that older CKD patients demonstrated more
      profound structural and functional abnormalities of the myocardium, as well as
      more prominent vascular changes compared to younger CKD patients. The changes in
      IMT, LVMI, and E/A ratio are independently associated with aging of CKD patients.

PMID- 28748885
TI  - Cardiac status in children with acute poststreptococcal glomerulonephritis.
AB  - Acute poststreptococcal glomerulonephritis (PSGN) is the most common type of
      glomerulonephritis seen in children. It can affect multiple organs with heart
      being frequently involved. Yet, there are very few studies on cardiac status in
      children with PSGN and hence this study was conducted. All consecutive children
      from 1 month to 12 years of age, admitted over a two-year period with a diagnosis
      of PSGN, were included in the study. An electrocardiogram (ECG) and two
      dimensional echocardiogram were performed in all patients on admission and
      repeated at six and 12 weeks, if abnormal. A total of thirty patients (18 males
      and 12 females) were enrolled in the study. The median age was six years.
      Prolonged QTc interval was found in 11 patients (37 %), of whom nine had
      hypertension. Seven of the 30 patients had a left ventricular ejection fraction
      (LVEF) <60%. The same patients also had left atrium/aorta ratio >2 and E/A ratio
      >2. LVEF returned to normal by six weeks in all except one patient, in whom it
      was normal by 12 weeks. Two of seven patients with low LVEF had normal blood
      pressure. All the seven patients recovered completely on follow-up. ECG and
      echocardiographic abnormalities may be seen in the acute phase of PSGN but are
      usually transient, returning to normal in most patients by three months. Although
      hypertension is the most common cause of cardiac failure, the role of primary
      myocardial dysfunction should also be considered.

PMID- 28748886
TI  - Clinical and histological correlation of diabetic nephropathy.
AB  - Renal failure in diabetes is a common cause of renal replacement therapy. The
      affected kidney goes through various changes in all compartments progressively.
      The classification of diabetic nephropathy is based on glomerular lesions and
      displays a heterogeneous morphology. Abnormalities in tubulointerstitial and
      vascular compartments are important in assessing the outcome of these patients.
      We applied the new pathologic classification of diabetic nephropathy by Tervaert
      et al to classify the renal damage in diabetes. This is a prospective study over
      two years. We analyzed 74 renal biopsies in diabetic patients, both type-1 and
      type-2. Indications for biopsy were rapid onset of proteinuria, absence of
      retinopathy, presence of hematuria, active urine sediment, and rapid unexplained
      deterioration of renal function. Biopsy was done to rule out nondiabetic renal
      disease or any other associated pathology with diabetic nephropathy. In our
      study, 53 patients were male and 21 patients were female. Age ranged from 27 to
      82 years. The mean +/- standard deviation age at the time of the biopsy was 54.09
      +/- 11.59 years. Mean duration of diabetes was 10.2 years. Proteinuria ranged
      from 1 to 26 g. Type-111 histopathological lesion was the most common lesion
      observed in our series. There was a correlation between the degree of tubulo
      interstitial damage with renal function. There was no correlation between the
      fundal changes and degree of proteinuria with the histological class of diabetic
      nephropathy. Application of the classification by Tervaert et al to diabetic
      lesions reduces the inter-observer variability and also helps in prognosticating
      and management of patients.

PMID- 28748887
TI  - Nondiabetic renal disease in patients with type 2 diabetes.
AB  - Diabetic nephropathy (DN) is one of the major complications of type 2 diabetes
      mellitus (T2DM). The diagnosis of DN is mostly clinical. Kidney biopsy is
      indicated only if nondiabetic renal disease (NDRD) is suspected. This study is
      aimed to assess the prevalence of NDRD and to determine predictor and prognostic
      factors of DN, NDRD. It was a retrospective analytic study including T2DM
      patients in whom renal biopsies were performed at our department from 1988 to
      2014. Seventy-five patients were included. Mean age was 52.7 years with sex ratio
      at 1.56. Renal biopsy findings were isolated NDRD in 33 cases, NDRD superimposed
      on DN in 24 cases, and isolated DN in 18 cases. Most common NDRD found were focal
      segmental glomerulosclerosis (21%) and membranous nephropathy (19%). Multivariate
      analysis showed that the absence of ischemic heart disease [odds ratio (OR) =
      0.178, 95% confidence interval (CI) = 0.041-0.762], absence of peripheral
      vascular disease (OR = 0.173, 95% CI = 0.045-0.669), and presence of hematuria
      (OR = 7.200, 95%CI = 0.886-58.531) were independent predictors of NDRD. 24
      patients reached end-stage renal disease 55% in DN group, 16% in DN associated to
      NDRD group, and 30% in NDRD group. The prevalence of NDRD found in our study
      confirmed usefulness of renal biopsy in patients with T2DM, especially in those
      without degenerative complications, hypertension, and insulin therapy.

PMID- 28748888
TI  - Childhood idiopathic steroid-resistant nephrotic syndrome at a Single Center in
      Khartoum.
AB  - Prevalence, clinicopathological features, and outcome of childhood idiopathic
      steroid-resistant nephrotic syndrome (ISRNS) vary in different countries. We
      report on these parameters in a single center in Khartoum. We retrospectively
      reviewed all the records of children with idiopathic nephrotic syndrome (INS)
      followed up in the pediatric renal unit, Soba Hospital, Khartoum between 2001 and
      2012. ISRNS was defined as no remission within four weeks of daily prednisolone
      at a dose of 60 mg/m2. In 430 children with INS 130 (28%) had SRNS with a mean
      age of 7.7 +/- 4.12 years. Males were 78 (60%). At presentation, hematuria was
      recorded in 57%, hypertension was recorded in 48%, and renal impairment in 15%.
      Histopathology showed focal segmental glomerulosclerosis in 40.8%,
      mesangioproliferative glomerulonephritis (22.3%), mesangiocapillary
      glomerulonephritis (16.9%), minimal change disease (MCD) (16.2%), and membranous
      glomerulonephritis (3.8%). Therapy included cyclosporine in 38.5%, additional
      therapy with cyclophosphamide, mycophenolate mofetil or tacrolimus in 20.8%, and
      steroids +/- diuretics +/- angiotensin converting enzyme (ACE) inhibitors in
      40.7%. After 3.64 +/- 2.84 years, 26.8% had complete remission (CR), 18.6%
      partial remission (PR), 26.8% were unremitting, 21.5% had chronic kidney disease
      (CKD), 1.6% died, and 4.6% were lost to follow-up. Non-MCD cases had
      significantly lower CR and higher CKD rates than MCD (P = 0.047 and 0.041,
      respectively). Cyclosporine +/- additional therapy was significantly associated
      with higher rate of CR than steroids +/- ACE inhibitors +/- diuretics (P =
      0.001), but the prevalence of CKD between the two groups was not significantly
      different (P = 0.604). Impaired renal function and hypertension at presentation
      were risk factors for CKD (P = 0.001 and 0.001, respectively). In Sudanese
      children with ISRNS, non-MCD lesions were the most common lesions. This pattern
      in addition to the lack of adequate therapy may explain the relatively lower CR
      and higher CKD rates. Impaired renal function and hypertension at presentation
      were risk factors for progression to CKD.

PMID- 28748889
TI  - Spectrum of kidney diseases in patients presented for acute hemodialysis in Kasr
      Al-Aini School of Medicine.
AB  - Acute kidney injury (AKI) is common in hospitalized patients with mortality
      varying from 10% to 80%. It is crucial to know the incidence and etiology of AKI
      to promote prevention strategies. Our study aimed at obtaining a comprehensive
      review of the pattern and spectrum of patients who presented for emergency
      hemodialysis to Kasr Al-Aini Hospital between October 2012 and October 2014. We
      analyzed clinical and laboratory factors in all such patients. Two thousand
      twenty three patients were included of which patients with AKI were 728 patients
      (36%). Cardiac diseases were the cause of AKI in 171 patients, other prerenal
      causes were found in 55 patients, drug induced AKI in 113 patients, and obstetric
      causes in 48 patients. Glomerulonephritis was responsible for AKI in 101
      patients, lupus nephritis was found in 33 patients of them. Patients with chronic
      kidney disease who presented with acute exacerbation were 243 patients (12%).
      Patients who were discovered to be with end-stage renal disease during their
      first presentation itself were 1052 patients (52 %). Diabetes mellitus was
      present in 50.12%, while hypertension was present in 29.56%. Hepatitis C virus
      was present in 17.3%, while HBsAg was present in 0.8%. Drugs and obstetric causes
      represented a larger fraction among our cases than seen in developed countries.
      Lupus nephritis was also a common cause of AKI.

PMID- 28748890
TI  - Prevalence of Hepatitis B core antibodies with negative Hepatitis B surface
      antigen in dialysis and chronic kidney disease patients.
AB  - Occult hepatitis B infection (OBI) is a potential cause of infection transmission
      in patients with chronic kidney disease (CKD) and dialysis-dependant patients. It
      is liable to be missed since the marker for OBI, hepatitis B core antibody
      (HBcAb), is not done routinely. We carried out a study to assess the prevalence
      of OBI in CKD Stage II-V or requiring renal replacement therapy. It was a cross
      sectional study carried out at Fatima Memorial Hospital, Lahore, from May 2104 to
      May 2015. A total of 188 patients were included in this study, 124 were dialysis
      dependent and 64 had acute or CKD Stage II-V. About 17.55% (n = 33) of patients
      had isolated HBcAb positive. Nearly 33.5% (n = 63) of patients were found to have
      hepatitis B surface antigen positive, indicating development of immunity by
      exposure to virus. About 20.74% (n = 39) of patients were co-positive with HBcAb
      also. The prevalence of isolated HBcAb in dialysis and CKD patients is high;
      therefore, testing for HBcAb should be a routine part of screening in our CKD
      population to rule out OBI. Further confirmation with polymerase chain reaction
      analysis for HBV viral DNA is recommended. Considering our circumstances, a
      consensus statement from the hepatologists and nephrologists is needed to further
      plan for the management of such cases.

PMID- 28748891
TI  - Study of chronic kidney disease-mineral bone disorders in newly detected advanced
      renal failure patients: A Hospital-based cross-sectional study.
AB  - We aim to evaluate the disturbances in mineral metabolism, abnormalities in bone
      mineral density (BMD), and extraskeletal calcification in newly detected,
      untreated predialysis stage 4 and 5 chronic kidney disease (CKD) patients at a
      tertiary care hospital in North India. This is cross-sectional observational
      study. A total of 95 (68 males, 27 females) newly detected patients underwent
      clinical evaluation, biochemical assessment [serum calcium, phosphorus, alkaline
      phosphatase (ALP), albumin, creatinine, intact parathyroid hormone (iPTH), 25-
      hydroxyvitamin D (25(OH)D)], BMD measurement (at spine, hip, and forearm) by dual
      energy X-ray absorptiometry (DXA), lateral abdominal radiograph [for abdominal
      aortic calcification (AAC)], skeletal survey (to look for any abnormality
      including fractures), and echocardiography [for any cardiac valvular
      calcification (CVC)]. Symptoms related to CKD-mineral bone disorder were seen in
      33.6% of the study patients. Prevalence of hypocalcemia, hyperphosphatemia,
      hyperparathyroidism, and hypovitaminosis D was 64.2%, 81.1%, 49.5%, and 89.5%,
      respectively. CVC was seen in 22.1% of patients on echocardiography, mostly
      involving the mitral valve. Patients with CVC were more likely to be males and
      smokers. There was no significant difference in iPTH levels between patients with
      or without CVC. AAC was seen in 10.5% of patients on lateral abdominal X-ray.
      Patients with AAC had higher levels of iPTH, phosphorus, and ALP and lower levels
      of calcium compared to patients without AAC. BMD by DXA showed a low bone mass in
      41.05% of our patients and was more prevalent in CKD stage 5. Most of the study
      patients had hyperparathyroidism and low 25(OH)D levels. Our study shows that
      newly detected, naive Indian CKD patients have a high prevalence of disturbances
      of mineral metabolism including hyperparathyroidism, Vitamin D deficiency,
      abnormal BMD, and valvular and vascular calcification, even before initiating
      dialysis.

PMID- 28748892
TI  - Clinical profile of geriatric acute kidney injury in a tertiary care center from
      south India.
AB  - The incidence of acute kidney injury (AKI) is high in the elderly, who comprise
      an ever-growing segment of the population. Elderly patients pose a different set
      of diagnostic and therapeutic challenge owing to their associated comorbidities.
      AKI in the elderly is associated with an increased risk of mortality, morbidity,
      prolonged length of stay, and progression to chronic kidney disease. Data
      regarding the clinical profile of AKI in the elderly from the South Indian
      population are limited. Hence, we present this analysis of the etiological and
      prognostic factors associated with AKI in elderly population from South India.
      This is a cross-sectional, prospective, observational study conducted in a
      tertiary care teaching hospital from Bengaluru, during the period from May 2011
      to October 2012. Institutional Ethical Committee clearance was obtained. Informed
      consents were obtained from patients who fulfilled the inclusion criteria.
      Elderly patients >60 years of age with features of AKI (Risk, Injury, Failure,
      Loss, and End-stage criteria) 1 at admission and those who developed AKI
      following hospital admission were included in the study. Demographic details,
      detailed medical history, comorbid conditions, etiological factors, prognostic
      factors, and outcomes were collected. Statistical analysis was done using
      Statistical Package for the Social Sciences software. Two hundred patients
      fulfilled the inclusion criteria and were enrolled into the study. The mean age
      was 70.5 years. Fifty-nine percent were males and 41% were females. Peak
      incidence of AKI was in the age group 60-69 years. Diabetes was seen in 44%,
      hypertension in 35%, ischemic heart disease in 19%, and chronic obstructive
      pulmonary disease in 12% of cases. Ninety-one percent had AKI at admission, and
      the rest developed it during hospitalization. The average duration of hospital
      stay was seven days. Etiological factors for AKI were medical in 87% of the
      cases, surgical in 11%, and gynecological in 2%. Sepsis was the most common
      etiology of AKI among the medical cases. Among sepsis, pneumonia and urosepsis
      were the most common causes of AKI. Medical AKI had a better outcome compared to
      surgical causes of AKI. Fifty-six (28%) patients required dialysis. Forty-four
      patients received hemodialysis and 12 received peritoneal dialysis. The overall
      mortality in the study group was 15%. Mortality among oliguric AKI (25%) was
      higher than in nonoliguric AKI (5%) patients (P = 0.002). The mortality rate was
      higher among postsurgical AKI compared to the medical causes (P <0.001) and in
      patients who required dialysis. Sepsis is the most common cause of AKI in elderly
      with high morbidity and mortality. Oliguria, postsurgical AKI, and need for
      dialysis were independent predictors of mortality.

PMID- 28748893
TI  - Complication rate and diagnostic yield of percutaneous native kidney biopsies: A
      10-year experience at a Tertiary Care Hospital in Pakistan.
AB  - The use of an automated biopsy device, and real-time ultrasound for percutaneous
      kidney biopsies (PKBs) has improved the likelihood of obtaining adequate tissue
      for diagnosis and also has reduced the complications associated with the
      procedure. We aimed to determine the frequency and type of complications
      associated with PKB and to determine the diagnostic yield. It was a retrospective
      file-based review of cases who underwent PKB of native kidney between January
      2003 and December 2013 at the Aga Khan University Hospital in Karachi, Pakistan.
      PKBs were performed by trained nephrologists or radiologists using an automated
      device with a 16/18-gauge needle under real-time ultrasound. The data obtained
      included age, gender, clinical and histopathological diagnosis, and complications
      associated with the procedure (minor: hematuria, local infections, and hematoma;
      major: transfusions, severe infections, surgery, nephrectomy, arteriography,
      embolism, and death. Yield of the procedure was based on the number of glomeruli
      obtained. Patients having major complications were compared with the patients who
      had minor or no complications. A total of 433 native kidney biopsies were
      performed. The mean age of the patients was 41 +/- 15.9 years, and 58% of the
      patients were male. The main histological findings were membranoproliferative
      glomerulonephritis (17.6%) followed by focal and segmental glomerulosclerosis
      (16.4%) and interstitial nephritis (13.9%). Majority of the procedures were
      performed by nephrologists (67.4%). The overall complication rate was 14.2%.
      Among those, 21 patients (4.8%) had a major complication while the others had
      minor complications. Of those who had a major complication, 17 patients required
      blood transfusion(s) and had hematuria or a major hematoma, three had prolonged
      hospitalization >24 hours, and one patient required surgical intervention. Only
      10 procedures (2.3%) had inadequate tissue to establish the histopathologic
      diagnosis. PKB under real-time ultrasound guidance is a safe and efficacious
      procedure to establish the histological diagnosis of the renal disease.

PMID- 28748894
TI  - Collagenofibrotic (Collagen Type III) glomerulopathy in association with diabetic
      nephropathy.
AB  - Collagenofibrotic (collagen type III) glomerulopathy (CG) is a rare nonimmune
      mediated glomerular disease. It is characterized by massive deposition of
      organized collagen type III fibers, which is localized in the mesangial and
      subendothelial glomerular areas and associated with increased serum levels of
      procollagen type III peptide. Association with systemic diseases and malignancies
      is extremely rare. Herein, we present a case of a nine-year-old girl, known case
      of type I diabetes mellitus, who presented with fever, nephrotic range
      proteinuria, generalized edema, and hypertension. Clinical examination did not
      show nail abnormalities or bone abnormalities. Renal biopsy revealed mesangial
      expansion and remarkable narrowing and obliteration of the glomerular capillaries
      by pale, amorphous material. Immunohistochemical study demonstrated diffuse
      linear glomerular capillary and tubular basement membrane staining for
      immunoglobulin G (IgG) and albumin. Ultrastructural examination identified
      massive mesangial and sub-endothelial deposition of dense frayed, curvilinear
      banded fibers with characteristic features of type III collagen. The patient was
      diagnosed to have combined CG and diabetic nephropathy (DN). This is the first
      report of CG in association with diabetic changes in renal biopsy. In this
      report, we describe the clinicopathological characteristics of this disease,
      review CG in pediatric population, and explore its association with DN.

PMID- 28748895
TI  - A case of severe carbamazepine overdose treated successfully with combined
      hemoperfusion and hemodialysis technique.
AB  - Carbamazepine intoxication manifests as altered mental status ranging from
      drowsiness to a coma and/or cardiac abnormalities such as sinus tachycardia,
      prolongation of the QRS interval, ventricular tachycardia, and hypotension. The
      patient may be agitated, but central nervous system (CNS) depression and
      presentation with coma is more common and could be lethal. Serious CNS toxicity
      often requires hemoperfusion and/or hemodialysis (HD). Herein, we present a case
      of a comatose patient, who was treated with a combination of hemoperfusion and HD
      in series. Our approach to treat the patient with a combination of hemoperfusion
      and HD was based on evidence from the literature supporting that the
      hemoperfusion and HD in series might provide the best clearance of carbamazepine.

PMID- 28748896
TI  - Sickled erythrocytes in urine as a clue to the diagnosis of sickle cell trait.
AB  - Sickled erythrocytes in patients of sickle cell trait with microscopic hematuria
      have rarely been reported so far. A 30-year-old female underwent delivery of a
      healthy full-term baby by cesarean section. However, postcesarean, she had pain
      in abdomen and fever, for which she was advised blood and urine examination. The
      hemogram suggested mild leukocytosis with neutrophilia and the urine showed red
      blood cells, some of which were sickled. The patient was advised hemoglobin
      electrophoresis which suggested sickle cell trait (Hb-AS). We conclude that
      sickled erythrocytes should not be ignored in a sample of urine as it may serve
      as an important clue to the diagnosis of sickle cell trait or disease.

PMID- 28748897
TI  - Milk-Alkali syndrome induced by H1N1 influenza vaccine.
AB  - Milk-Alkali syndrome (MAS) consists of a triad of hypercalcemia, metabolic
      alkalosis, and acute renal failure. We hereby report a 75-year-old Indian
      gentleman who presented to our emergency department with a history of generalized
      weakness and easy fatigability. Investigations were consistent with MAS secondary
      to calcium carbonate and calcitriol treatment to prevent osteoporosis, aggravated
      by H1N1 influenza vaccine. The patient was treated with hemodialysis and
      zoledronate. To our knowledge, this is the first reported case of such
      association in the literature.

PMID- 28748898
TI  - Unilateral multicystic renal dysplasia: Prenatal diagnosis on ultrasound.
AB  - Multicystic renal dysplasia (MCRD) is the most common cause of abnormally
      enlarged kidney, diagnosed on antenatal ultrasound examination. It is an
      abnormality of the embryonic development in which the renal parenchyma is
      substituted by nonfunctioning renal tissue made up of cysts which do not
      communicate with each other. Vesicoureteric reflux (VUR), pelviureteric junction
      obstruction, vesicoureteric junction obstruction, and ureterocele are the most
      commonly seen abnormalities in contralateral kidney. Here, we report a case of
      prenatal diagnosis of unilateral MCRD with VUR in contralateral kidney. In
      conclusion, we want to emphasize optimal use of ultrasound imaging to detect such
      abnormalities as early as possible to guide the proper management.

PMID- 28748899
TI  - Primary intracranial leiomyoma in renal transplant recipient.
AB  - Leiomyoma, the benign tumor of smooth muscle cell origin, is commonly seen in
      genitourinary and gastrointestinal tracts. Primary intracranial leiomyoma,
      however, is extremely rare occurrence. We hereby report a case of Epstein-Barr
      negative primary intracranial leiomyoma in a middle-aged renal transplant
      recipient, which mimicked left frontal parasagittal meningioma on neuroimaging.
      The tumor was completely excised and diagnosis of leiomyoma was clinched on
      pathological analysis with immunohistochemistry. The patient improved after tumor
      removal, and no evidence of tumor recurrence was noted on follow-up study after
      10 months postsurgically.

PMID- 28748900
TI  - Dense deposit disease in a child with febrile sore throat.
AB  - Dense deposit disease or membranoproliferative glomerulonephritis type II is a
      rare glomerulopathy characterized on renal biopsy by deposition of abnormal
      electron-dense material in the glomerular basement membrane. The pathophysiologic
      basis is uncontrolled systemic activation of the alternate pathway of the
      complement cascade. C3 nephritic factor, an autoantibody directed against the C3
      convertase of the alternate pathway, plays a key role. In some patients,
      complement gene mutations have been identified. We report the case of a child who
      had persistent microscopic hematuria, proteinuria, and hypocomplementemia C3 for
      over 2 months. Renal biopsy confirmed the diagnosis of dense deposit disease.

PMID- 28748901
TI  - Renal manifestations in hypocomplementic urticarial vasculitis syndrome: Is it a
      distinct pathology?
AB  - Hypocomplementic urticarial vasculitis syndrome (HUVS) is an autoimmune disease
      characterized by recurrent urticaria, arthritis, and glomerulonephritis (GN).
      Anti-C1q antibody is the marker of HUVS together with low levels of classical
      pathway complements which are C2, C3, C4, and C1q. We report a case of a 6-year
      old boy who presented with episodes of rashes, injected conjunctiva, abdominal
      pain, and arthritis, diagnosed as HUVS. He had low C3, low CH50, normal C4, and
      positive C1q antibody. His urinalysis showed intermittent microscopic hematuria
      only. One year later, his laboratories showed persistent low C3 and positive Anti
      ds DNA. The urinalysis showed hematuria, pyuria, and nephrotic-range proteinuria.
      Urine protein to creatinine ratio was 101.8 h mg/mmol. Kidney biopsy showed
      mesangioproliferative GN consistent with the diagnosis of HUVS. The patient was
      treated initially with prednisolone then azathioprine was added to the regimen.
      He showed good response with the disappearance of hematuria and proteinuria. Nine
      months later, he had no skin rashes with normal urinalysis and normal anti-ds DNA
      antibody. We report a case with HUVS and GN with positive anti-dsDNA antibody
      that revealed good response to combination of immunosuppressive therapy.

PMID- 28748902
TI  - Acute renal failure secondary to drug-related crystalluria and/or drug reaction
      with eosinophilia and systemic symptom syndrome in a patient with metastatic lung
      cancer.
AB  - Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced
      hypersensitivity is a severe adverse drug-induced reaction. Aromatic
      anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, and some
      drugs, can induce DRESS. Atypical crystalluria can be seen in patients treated
      with amoxycillin or some drugs and can cause acute renal failure. We describe a
      66-year-old man who presented fever and rash and acute renal failure three days
      after starting amoxycillin. He was also using phenytoin because of cerebral
      metastatic lung cancer. Investigation revealed eosinophilia and atypical
      crystalluria. The diagnosis of DRESS syndrome was made, amoxicillin was stopped,
      and dose of phenytoin was reduced. No systemic corticosteroid therapy was
      prescribed. Symptoms began to resolve within three to four days. The aim of this
      paper is to highlight the importance of microscopic examination of urine in a
      case with acute renal failure and skin lesions to suspect DRESS syndrome.

PMID- 28748903
TI  - Immunoglobulin A nephropathy in a patient with IgG kappa light-chain myeloma.
AB  - Paraproteins can cause a variable set of pathologic changes in the kidney. The
      introduction of novel anti-plasma cell agents capable of reversing renal failure
      have revolutionized the management of paraprotein-mediated kidney injury.
      Activation of the transcription factor nuclear factor kB (NF-kB) has been shown
      to be involved in the development of human glomerulonephritis (GN). Inhibitors of
      NF-kB may provide potential agents for treatment of immune complex GN. In this
      paper, we report a patient with IgA nephropathy and IgG kappa myeloma, who
      responded dramatically to chemotherapy targeted toward myeloma. Our findings
      support the idea that drugs modulating NF-kB may add another dimension to the
      management of IgA nephropathy.

PMID- 28748904
TI  - Native kidney posttransplant lymphoproliferative disorder in a renal transplant
      recipient.
AB  - Compared with the general population, cancer risk in kidney transplant recipients
      is much higher. In the present study, we report a patient who was diagnosed with
      posttransplant lymphoproliferative disorder (PTLD) and had a fulminant course,
      dying within few days of diagnosis. This case report highlights the importance of
      timely detection and treatment of PTLD as it is associated with high mortality
      rate.

PMID- 28748905
TI  - The importance of calciuria on sodium fractional excretion rate.

PMID- 28748906
TI  - Solid organ transplantation and zika virus infection.

PMID- 28748907
TI  - Cost analysis for renal dialysis: Case study from Indochina.

PMID- 28748908
TI  - Natural history of de novo High Grade Glioma: first description of growth
      parabola.
AB  - Etiopathogenesis and physiopathology of gliomas are largely unknown. Recently,
      many authors have proved a strict correlation between the velocity of diametric
      expansion (VDE) on the Magnetic Resonance Imaging (MRI) and the biological
      behavior of these tumors, especially in Low Grade Gliomas (LGGs). Unfortunately,
      natural history of High Grade Gliomas (HGGs) has not been well clarified because
      of its fast progression, late diagnoses and early surgical intervention. We
      describe, for the first time to our knowledge, the case of asymptomatic patient
      with an incidentally discovered de novo HGG with a total of 17 months of follow
      up. A male patient was referred to our consultation for routinely follow-up after
      meningioma resection 5 years before. He underwent MRI every year without any
      neuroradiological alterations. A new MRI image presented a non-enhancing lesion
      in the right temporal lobe with 3.55 cm of Mean Tumor Diameter (MTD) and 35.6
      mm/year of VDE. After two months interval, the lesion had 3.97 cm of MTD and 27.8
      mm/year of VDE. Although we have strongly suggested surgical resection, patient
      have delayed the operation for personal issues. After other 3 months, the tumor
      showed enhancement with 4.5 of MTD and 17.4 mm/year of VDE. We speculate that the
      descending parabola is due to initial mass effect and hypoxia of the tumor core.
      We also underline the crucial role of the VDE determining, in order to predict
      the nature of the lesion and address the most effective treatment for each
      patient.

PMID- 28748909
TI  - Von Hippel-Lindau disease: when neurosurgery meets nephrology, ophthalmology and
      genetics.
AB  - INTRODUCTION: Von Hippel-Lindau (VHL) disease is a dominantly inherited condition
      associated with tumors in multiple organs, whose treatment requires heightened
      multidisciplinary teamwork. Therefore, a document summarizing all the pertinent
      knowledge is needed to enhance coordination of care. EVIDENCE ACQUISITION: A
      systematic review of the literature from the Medline, Embase and Cochrane Central
      databases was performed. From 1970 to 2017, all articles meeting specific
      inclusion criteria were included by at least one specialist physician for each
      field. EVIDENCE SYNTHESIS: We included 95 articles, mostly dealing with genetics
      or management of VHL associated tumors in one organ system. There were no papers
      discussing the manifestations of VHL altogether, which was the aim of our paper.
      CONCLUSIONS: VHL requires a multidisciplinary management to provide the highest
      quality of care. Coordination and communication between patients and caregivers
      is enhanced when knowledge is shared. Gathering together specialists in different
      domains around the production and reading of a comprehensive document such as the
      one hereby may contribute to this purpose.

PMID- 28748910
TI  - Spinal intramedullary ependymoma: surgical approaches and outcome.
AB  - Intramedullary ependymomas are uncommon tumors that can occur within the
      medullary substance of the spinal cord. Despite this difficult location, they are
      typically benign tumors that can most often be removed completely with an
      acceptable surgical risk. Therefore, the recommended management approach is
      usually surgical excision. This review will consider the historical context in
      which surgeons began treating these tumors and then review the more recent
      literature that guides their current management.

PMID- 28748911
TI  - A novel and quick PCR-based method to genotype mice with a leptin receptor
      mutation (db/db mice).
AB  - db/db mice is one of most widely used animal models in studying the cellular and
      molecular mechanisms of metabolic disorders, such as diabetes, hyperlipidemia,
      and obesity. The mice carry spontaneous point mutations in the gene encoding the
      leptin receptor, leading to leptin receptor inactivation. Since homozygous db/db
      mice are sterile, the maintenance of db/db mice requires breeding between
      heterozygous pairs, which makes genotyping essential for the identification of
      offspring. The aim of this study was to develop a quick and highly repeatable
      method for genotyping db/db mice, which comprised only three simple steps:
      genomic DNA is extracted from either tail tips or ear notches via alkaline lysis
      (~20 min); samples are then subjected to tetra-primer amplification refractory
      mutation system-polymerase chain reaction (ARMS-PCR) using specially designed and
      validated primer sets (~1.5 h); finally, genotypes are be determined by resolving
      PCR products on regular DNA electrophoresis (~10 min). The entire db/db mice
      genotyping procedure can be performed using regular Taq polymerase and PCR
      amplification within 2 h. Other advantages of this method include high
      sensitivity and reproducibility. Minimal amounts of tissue from mice are
      required, and genomic DNA samples can be stably stored at room temperature for up
      to one month. In conclusion, the method is simple, cost effective, sensitive and
      reliable, which will greatly facilitate studies using db/db mice.

PMID- 28748912
TI  - A novel allosteric site in casein kinase 2alpha discovered using combining
      bioinformatics and biochemistry methods.
AB  - Casein kinase 2 (CK2) is a highly pleiotropic serine-threonine kinase, which
      catalyzed phosphorylation of more than 300 proteins that are implicated in
      regulation of many cellular functions, such as signal transduction,
      transcriptional control, apoptosis and the cell cycle. On the other hand, CK2 is
      abnormally elevated in a variety of tumors, and is considered as a promising
      therapeutic target. The currently available ATP-competitive CK2 inhibitors,
      however, lack selectivity, which has impeded their development in cancer therapy.
      Because allosteric inhibitors can avoid the shortcomings of conventional kinase
      inhibitors, this study was aimed to discover a new allosteric site in CK2alpha
      and to investigate the effects of mutations in this site on the activity of
      CK2alpha. Using Allosite based on protein dynamics and structural alignment, we
      predicted a new allosteric site that was partly located in the alphaC helix of
      CK2alpha. Five residues exposed on the surface of this site were mutated to
      validate the prediction. Kinetic analyses were performed using a luminescent ADP
      detection assay by varying the concentrations of a peptide substrate, and the
      results showed that the mutations I78C and I78W decreased CK2alpha activity,
      whereas V31R, K75E, I82C and P109C increased CK2alpha activity. Potential
      allosteric pathways were identified using the Monte Carlo path generation
      approach, and the results of these predicted allosteric pathways were consistent
      with the mutation analysis. Multiple sequence alignments of CK2alpha with the
      other kinases in the family were conducted using the ClustalX method, which
      revealed the diversity of the residues in the site. In conclusion, we identified
      a new allosteric site in CK2alpha that can be altered to modulate the activity of
      the kinase. Because of the high diversity of the residues in the site, the site
      can be targeted using rational drug design of specific CK2alpha inhibitors for
      biological relevance.

PMID- 28748913
TI  - D-chiro-inositol effectively attenuates cholestasis in bile duct ligated rats by
      improving bile acid secretion and attenuating oxidative stress.
AB  - Cholestatic liver diseases are important causes of liver cirrhosis and liver
      transplantation, but few drugs are available for treatment. D-chiro-inositol
      (DCI), an isomer of inositol found in many Leguminosae plants and in animal
      viscera, is used clinically for the treatment of polycystic ovary syndrome (PCOS)
      and diabetes mellitus. In this study, we investigated whether DCI exerted an anti
      cholestatic effect and its underlying mechanisms. A cholestatic rat model was
      established via bile duct ligation (BDL). After the surgery, the rats were given
      DCI (150 mg.kg-1.d-1) in drinking water for 2 weeks. Oral administration of DCI
      significantly decreased the serum levels of alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST), and attenuated bile duct proliferation,
      parenchymal necrosis and fibrosis in BDL rats. Furthermore, DCI treatment
      significantly increased the serum and bile levels of total bile acid (TBA), and
      decreased TBA levels in the liver. Moreover, DCI treatment significantly
      increased expression of the genes encoding bile acid transporters BSEP (Abcb11)
      and MRP2 (Abcc2) in liver tissues. DCI treatment also markedly decreased hepatic
      CD68 and NF-kappaB (NF-kappaB) levels, significantly decreased the serum and
      hepatic MDA levels, markedly increased superoxide dismutase activity in both
      serum and liver tissues. Using whole-genome oligonucleotide microarray, we
      revealed that DCI treatment altered the expression profiles of oxidation
      reduction-related genes in liver tissues. Collectively, DCI effectively
      attenuates BDL-induced hepatic bile acid accumulation and decreases the severity
      of injury and fibrosis by improving bile acid secretion, repressing inflammation
      and decreasing oxidative stress. The results suggest that DCI might be beneficial
      for patients with cholestatic disorders.

PMID- 28748914
TI  - Association of bone turnover markers with glucose metabolism in Chinese
      population.
AB  - The association between type 2 diabetes (T2DM) and bone metabolism has been
      discussed previously but is controversial. In this study we aimed to evaluate the
      association of bone turnover markers with glucose metabolism in Chinese
      population, in which 919 males and 4171 postmenopausal females in a region of
      Shanghai were recruited. Anthropometric and biochemical traits related to glucose
      and bone metabolism were analyzed. Participants were classified according to
      their glucose tolerance as normal glucose tolerance (NGT), impaired glucose
      regulation (IGR) or T2DM. Males and females were analyzed separately, and then
      associations between bone turnover markers (BTMs) and glucose metabolism were
      evaluated. The results showed that in females, the serum levels of N-terminal
      osteocalcin (N-MID), N-terminal procollagen of type I collagen (PINP) and beta
      cross-linked C-telopeptide of type I collagen (beta-CTX) were significantly
      decreased in the T2DM group compared to the NGT group (P<0.01). When age, body
      mass index, serum lipids, fat percentage, visceral fat area, subcutaneous fat
      area, anti-diabetic medicines, PINP, N-MID and beta-CTX were included in one
      logistic model, N-MID (OR [95% CI]: 0.954 [0.932; 0.976]; P=0.0001) was
      significantly associated with T2DM in females. In females, N-MID was associated
      with insulin sensitivity and HOMA-beta. PINP was significantly associated with
      HOMA-beta, GUTT-ISI, Stumvoll first-phase insulin secretion index (STU-1) and
      Stumvoll second-phase insulin secretion index (STU-2), but beta-CTX was
      associated only with HOMA-beta (beta+/-SE: 0.1331+/-0.0311; P=1.95*10-5) and GUTT
      ISI (beta+/-SE: 0.0727+/-0.0229; P=0.0015). In males, N-MID was significantly
      correlated with HOMA-beta (beta+/-SE: 0.3439+/-0.0633; P=7.75*10-8), GUTT-ISI
      (beta+/-SE: 0.1601+/-0.0531; P=0.0027) and STU-1 (beta+/-SE: 0.2529+/-0.1033;
      P=0.0146). Significant associations were also detected between beta-CTX and HOMA
      beta (beta+/-SE: 0.2736+/-0.0812; P=0.0009). This study reveals that BTMs are
      highly associated with T2DM, insulin sensitivity and beta cell function in both
      Chinese males and postmenopausal females.

PMID- 28748915
TI  - The endoplasmic reticulum stress-autophagy pathway is involved in apelin-13
      induced cardiomyocyte hypertrophy in vitro.
AB  - Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays
      important roles in the cardiovascular system. Our previous studies showed that
      apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K
      autophagy pathway. The aim of this study was to explore what roles ER stress and
      autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro.
      Treatment of H9c2 cells with apelin-13 (0.001-2 MUmol/L) dose-dependently
      increased the production of ROS and the expression levels of NADPH oxidase 4
      (NOX4). Knockdown of Nox4 with siRNAs effectively prevented the reduction of
      GSH/GSSG ratio in apelin-13-treated cells. Furthermore, apelin-13 treatment dose
      dependently increased the expression of Bip and CHOP, two ER stress markers, in
      the cells. Knockdown of APJ or Nox4 with the corresponding siRNAs, or application
      of NADPH inhibitor DPI blocked apelin-13-induced increases in Bip and CHOP
      expression. Moreover, apelin-13 treatment increased the formation of
      autophagosome and ER fragments and the LC3 puncta in the ER of the cells.
      Knockdown of APJ, Nox4, Bip or CHOP with the corresponding siRNAs, or application
      of DPI or salubrinal attenuated apelin-13-induced overexpression of LC3-II/I and
      beclin 1. Finally, knockdown of Nox4, Bip or CHOP with the corresponding siRNAs,
      or application of salubrinal significantly suppressed apelin-13-induced increases
      in the cell diameter, volume and protein contents. Our results demonstrate that
      ER stress-autophagy is involved in apelin-13-induced H9c2 cell hypertrophy.

PMID- 28748916
TI  - Conformation and dynamics of the C-terminal region in human phosphoglycerate
      mutase 1.
AB  - Phosphoglycerate mutase 1 (PGAM1), an important enzyme in glycolysis, is
      overexpressed in a number of human cancers, thus has been proposed as a promising
      metabolic target for cancer treatments. The C-terminal portion of the available
      crystal structures of PGAM1 and its homologous proteins is partially disordered,
      as evidenced by weak electron density. In this study, we identified the
      conformational behavior of the C-terminal region of PGAM1 as well as its role
      during the catalytic cycle. Using the PONDR-FIT server, we demonstrated that the
      C-terminal region was intrinsically disordered. We applied the Monte Carlo (MC)
      method to explore the conformational space of the C-terminus and conducted a
      series of explicit-solvent molecular dynamics (MD) simulations, and revealed that
      the C-terminal region is inherently dynamic; large-scale conformational changes
      in the C-terminal segment led to the structural transition of PGAM1 from the
      closed state to the open state. Furthermore, the C-terminal segment influenced
      2,3-bisphosphoglycerate (2,3-BPG) binding. The proposed swing model illustrated a
      critical role of the C-terminus in the catalytic cycle through the conformational
      changes. In conclusion, the C-terminal region induces large movements of PGAM1
      from the closed state to the open state and influences cofactor binding during
      the catalytic cycle. This report describes the dynamic features of the C-terminal
      region in detail and should aid in design of novel and efficient inhibitors of
      PGAM1. A swing mechanism of the C-terminal region is proposed, to facilitate
      further studies of the catalytic mechanism and the physiological functions of its
      homologues.

PMID- 28748918
TI  - Different combinations of glucose tolerance and blood pressure status and
      incident cardiovascular disease and all-cause mortality events.
AB  - The purpose of this study was to evaluate the effect of combinations of blood
      pressure and glucose tolerance status on cardiovascular and all-cause mortality.
      A total of 7619 participants aged ?30 years old were stratified to nine
      categories as follows: (1) normotension (NTN) and normal glucose tolerance (NGT)
      (reference group), (2) NTN and pre-diabetes mellitus (pre-DM), (3) NTN and DM,
      (4) pre-hypertension (pre-HTN) and NGT, (5) pre-HTN and pre-DM, (6) pre-HTN and
      DM, (7) HTN and NGT, (8) HTN and pre-DM and (9) HTN and DM. Cox proportional
      hazards were applied to calculate the multivariate hazard ratios (HRs) of
      different groups for outcomes. For all-cause mortality outcomes, prevalent
      cardiovascular disease (CVD) was also adjusted. In a median follow-up of 11.3
      years, 696 CVD and 412 all-cause mortality events occurred. Among the population
      free from CVD at baseline (n=7249), presence of HTN was associated with increased
      risk of CVD, regardless of glucose tolerance status with HRs of 1.97 (95%
      confidence interval (CI), 1.49-2.61), 2.25 (1.68-3.02) and 3.16 (2.28-4.37) for
      phenotypes of HTN and NGT, HTN and pre-DM and HTN and DM for CVD, respectively;
      corresponding HRs for all-cause mortality were 1.65 (95% CI, 1.15-2.37), 1.69
      (1.15-2.49) and 2.73 (1.80-4.14), respectively. Phenotypes of NTN and pre-DM
      (1.48; 1.03-2.14) and NTN and DM (2.04; 1.06-3.92) were also associated with CVD
      and all-cause mortality, respectively. HTN was significantly associated with
      CVD/mortality events, regardless of glucose tolerance status. Blood pressure
      <120/80 mm Hg among pre-diabetic/diabetic population, not on antihypertensive
      medications, was generally associated with worse outcomes.

PMID- 28748919
TI  - Changing concepts in hypertension management.
AB  - Hypertension is the most common modifiable risk factor for cardiovascular disease
      and death, and lowering blood pressure with anti-hypertensive drugs reduces
      target organ damage and prevents cardiovascular disease outcomes. The recent
      trials SPRINT and HOPE-3 will lead to changes in the way we manage hypertension
      and impact on clinical practice guidelines. These studies also demonstrate the
      shift toward automated blood pressure measurements. We have reviewed these
      studies and others to put them in context with the guidelines that have come
      before and to describe how they will impact on hypertension treatment thresholds
      and targets, the treatment of hypertension in the elderly, and changing
      approaches to the management of hypertension including resistant hypertension.

PMID- 28748921
TI  - Erratum: Uniform electroactive fibre-like micelle nanowires for organic
      electronics.
AB  - This corrects the article DOI: 10.1038/ncomms15909.

PMID- 28748917
TI  - Oesophageal cancer.
AB  - Oesophageal cancer is the sixth most common cause of cancer-related death
      worldwide and is therefore a major global health challenge. The two major
      subtypes of oesophageal cancer are oesophageal squamous cell carcinoma (OSCC) and
      oesophageal adenocarcinoma (OAC), which are epidemiologically and biologically
      distinct. OSCC accounts for 90% of all cases of oesophageal cancer globally and
      is highly prevalent in the East, East Africa and South America. OAC is more
      common in developed countries than in developing countries. Preneoplastic lesions
      are identifiable for both OSCC and OAC; these are frequently amenable to
      endoscopic ablative therapies. Most patients with oesophageal cancer require
      extensive treatment, including chemotherapy, chemoradiotherapy and/or surgical
      resection. Patients with advanced or metastatic oesophageal cancer are treated
      with palliative chemotherapy; those who are human epidermal growth factor
      receptor 2 (HER2)-positive may also benefit from trastuzumab treatment. Immuno
      oncology therapies have also shown promising early results in OSCC and OAC. In
      this Primer, we review state-of-the-art knowledge on the biology and treatment of
      oesophageal cancer, including screening, endoscopic ablative therapies and
      emerging molecular targets, and we discuss best practices in chemotherapy,
      chemoradiotherapy, surgery and the maintenance of patient quality of life.

PMID- 28748923
TI  - Correction.

PMID- 28748922
TI  - Regulation of Drosophila hematopoietic sites by Activin-beta from active sensory
      neurons.
AB  - An outstanding question in animal development, tissue homeostasis and disease is
      how cell populations adapt to sensory inputs. During Drosophila larval
      development, hematopoietic sites are in direct contact with sensory neuron
      clusters of the peripheral nervous system (PNS), and blood cells (hemocytes)
      require the PNS for their survival and recruitment to these microenvironments,
      known as Hematopoietic Pockets. Here we report that Activin-beta, a TGF-beta
      family ligand, is expressed by sensory neurons of the PNS and regulates the
      proliferation and adhesion of hemocytes. These hemocyte responses depend on PNS
      activity, as shown by agonist treatment and transient silencing of sensory
      neurons. Activin-beta has a key role in this regulation, which is apparent from
      reporter expression and mutant analyses. This mechanism of local sensory neurons
      controlling blood cell adaptation invites evolutionary parallels with vertebrate
      hematopoietic progenitors and the independent myeloid system of tissue
      macrophages, whose regulation by local microenvironments remain undefined.

PMID- 28748924
TI  - Significant and variable linear polarization during the prompt optical flash of
      GRB 160625B.
AB  - Newly formed black holes of stellar mass launch collimated outflows (jets) of
      ionized matter that approach the speed of light. These outflows power prompt,
      brief and intense flashes of gamma-rays known as gamma-ray bursts (GRBs),
      followed by longer-lived afterglow radiation that is detected across the
      electromagnetic spectrum. Measuring the polarization of the observed GRB
      radiation provides a direct probe of the magnetic fields in the collimated jets.
      Rapid-response polarimetric observations of newly discovered bursts have probed
      the initial afterglow phase, and show that, minutes after the prompt emission has
      ended, the degree of linear polarization can be as high as 30 per cent-consistent
      with the idea that a stable, globally ordered magnetic field permeates the jet at
      large distances from the central source. By contrast, optical and gamma-ray
      observations during the prompt phase have led to discordant and often
      controversial results, and no definitive conclusions have been reached regarding
      the origin of the prompt radiation or the configuration of the magnetic field.
      Here we report the detection of substantial (8.3 +/- 0.8 per cent from our most
      conservative simulation), variable linear polarization of a prompt optical flash
      that accompanied the extremely energetic and long-lived prompt gamma-ray emission
      from GRB 160625B. Our measurements probe the structure of the magnetic field at
      an early stage of the jet, closer to its central black hole, and show that the
      prompt phase is produced via fast-cooling synchrotron radiation in a large-scale
      magnetic field that is advected from the black hole and distorted by dissipation
      processes within the jet.

PMID- 28748926
TI  - Thirty Meter Telescope: Alternative telescope site is a good back-up.

PMID- 28748927
TI  - Applied physics: A new spin on nanoscale computing.

PMID- 28748929
TI  - Open data: enforce materials sharing.

PMID- 28748930
TI  - Neuromorphic computing with nanoscale spintronic oscillators.
AB  - Neurons in the brain behave as nonlinear oscillators, which develop rhythmic
      activity and interact to process information. Taking inspiration from this
      behaviour to realize high-density, low-power neuromorphic computing will require
      very large numbers of nanoscale nonlinear oscillators. A simple estimation
      indicates that to fit 108 oscillators organized in a two-dimensional array inside
      a chip the size of a thumb, the lateral dimension of each oscillator must be
      smaller than one micrometre. However, nanoscale devices tend to be noisy and to
      lack the stability that is required to process data in a reliable way. For this
      reason, despite multiple theoretical proposals and several candidates, including
      memristive and superconducting oscillators, a proof of concept of neuromorphic
      computing using nanoscale oscillators has yet to be demonstrated. Here we show
      experimentally that a nanoscale spintronic oscillator (a magnetic tunnel
      junction) can be used to achieve spoken-digit recognition with an accuracy
      similar to that of state-of-the-art neural networks. We also determine the regime
      of magnetization dynamics that leads to the greatest performance. These results,
      combined with the ability of the spintronic oscillators to interact with each
      other, and their long lifetime and low energy consumption, open up a path to
      fast, parallel, on-chip computation based on networks of oscillators.

PMID- 28748931
TI  - Wilhelm et al. reply.

PMID- 28748932
TI  - Can we predict protein from mRNA levels?

PMID- 28748933
TI  - Spontaneous breaking of rotational symmetry in copper oxide superconductors.
AB  - The origin of high-temperature superconductivity in copper oxides and the nature
      of the 'normal' state above the critical temperature are widely debated. In
      underdoped copper oxides, this normal state hosts a pseudogap and other anomalous
      features; and in the overdoped materials, the standard Bardeen-Cooper-Schrieffer
      description fails, challenging the idea that the normal state is a simple Fermi
      liquid. To investigate these questions, we have studied the behaviour of single
      crystal La2-xSrxCuO4 films through which an electrical current is being passed.
      Here we report that a spontaneous voltage develops across the sample, transverse
      (orthogonal) to the electrical current. The dependence of this voltage on probe
      current, temperature, in-plane device orientation and doping shows that this
      behaviour is intrinsic, substantial, robust and present over a broad range of
      temperature and doping. If the current direction is rotated in-plane by an angle
      phi, the transverse voltage oscillates as sin(2phi), breaking the four-fold
      rotational symmetry of the crystal. The amplitude of the oscillations is strongly
      peaked near the critical temperature for superconductivity and decreases with
      increasing doping. We find that these phenomena are manifestations of unexpected
      in-plane anisotropy in the electronic transport. The films are very thin and
      epitaxially constrained to be tetragonal (that is, with four-fold symmetry), so
      one expects a constant resistivity and zero transverse voltage, for every phi.
      The origin of this anisotropy is purely electronic-the so-called electronic
      nematicity. Unusually, the nematic director is not aligned with the crystal axes,
      unless a substantial orthorhombic distortion is imposed. The fact that this
      anisotropy occurs in a material that exhibits high-temperature superconductivity
      may not be a coincidence.

PMID- 28748934
TI  - Synergy of synthesis, computation and NMR reveals correct baulamycin structures.
AB  - Small-molecule, biologically active natural products continue to be our most
      rewarding source of, and inspiration for, new medicines. Sometimes we happen upon
      such molecules in minute quantities in unique, difficult-to-reach, and often
      fleeting environments, perhaps never to be discovered again. In these cases,
      determining the structure of a molecule-including assigning its relative and
      absolute configurations-is paramount, enabling one to understand its biological
      activity. Molecules that comprise stereochemically complex acyclic and
      conformationally flexible carbon chains make such a task extremely challenging.
      The baulamycins (A and B) serve as a contemporary example. Isolated in small
      quantities and shown to have promising antimicrobial activity, the structure of
      the conformationally flexible molecules was determined largely through J-based
      configurational analysis, but has been found to be incorrect. Our subsequent
      campaign to identify the true structures of the baulamycins has revealed a
      powerful method for the rapid structural elucidation of such molecules.
      Specifically, the prediction of nuclear magnetic resonance (NMR) parameters
      through density functional theory-combined with an efficient sequence of boron
      based synthetic transformations, which allowed an encoded (labelled) mixture of
      natural-product diastereomers to be prepared-enabled us rapidly to pinpoint and
      synthesize the correct structures.

PMID- 28748935
TI  - Imaging: History's take on the atomic forge.

PMID- 28748936
TI  - Organic chemistry: Molecular structure assignment simplified.

PMID- 28748937
TI  - Biodiversity: Factor in species' conservation value.

PMID- 28748938
TI  - Open data: support from Swiss funder.

PMID- 28748939
TI  - Cell engineering: How to hack the genome.

PMID- 28748941
TI  - Correction.

PMID- 28748942
TI  - Global health: Towards polio eradication.

PMID- 28748943
TI  - Metrology is key to reproducing results.

PMID- 28748944
TI  - Iceland drilling project aims to unearth how islands form.

PMID- 28748945
TI  - China's quest to become a space science superpower.

PMID- 28748946
TI  - Giant radio telescope scaled back to contain costs.

PMID- 28748947
TI  - Put cult online games to the test.

PMID- 28748948
TI  - US defence agencies grapple with gene drives.

PMID- 28748949
TI  - Don't run biomedical science as a business.

PMID- 28748950
TI  - The digital native is a myth.

PMID- 28748951
TI  - HIV milestone, discrimination suit and China's AI plans.

PMID- 28748952
TI  - Budding UK innovation agency gains cash - and clout.

PMID- 28748953
TI  - Brain's stem cells slow ageing in mice.

PMID- 28748954
TI  - More universities must confront sexual harassment.

PMID- 28748955
TI  - Bayesian association scan reveals loci associated with human lifespan and linked
      biomarkers.
AB  - The enormous variation in human lifespan is in part due to a myriad of sequence
      variants, only a few of which have been revealed to date. Since many life
      shortening events are related to diseases, we developed a Mendelian randomization
      based method combining 58 disease-related GWA studies to derive longevity priors
      for all HapMap SNPs. A Bayesian association scan, informed by these priors, for
      parental age of death in the UK Biobank study (n=116,279) revealed 16 independent
      SNPs with significant Bayes factor at a 5% false discovery rate (FDR). Eleven of
      them replicate (5% FDR) in five independent longevity studies combined; all but
      three are depleted of the life-shortening alleles in older Biobank participants.
      Further analysis revealed that brain expression levels of nearby genes (RBM6,
      SULT1A1 and CHRNA5) might be causally implicated in longevity. Gene expression
      and caloric restriction experiments in model organisms confirm the conserved role
      for RBM6 and SULT1A1 in modulating lifespan.

PMID- 28748956
TI  - Thermally stable single atom Pt/m-Al2O3 for selective hydrogenation and CO
      oxidation.
AB  - Single-atom metal catalysts offer a promising way to utilize precious noble metal
      elements more effectively, provided that they are catalytically active and
      sufficiently stable. Herein, we report a synthetic strategy for Pt single-atom
      catalysts with outstanding stability in several reactions under demanding
      conditions. The Pt atoms are firmly anchored in the internal surface of
      mesoporous Al2O3, likely stabilized by coordinatively unsaturated pentahedral
      Al3+ centres. The catalyst keeps its structural integrity and excellent
      performance for the selective hydrogenation of 1,3-butadiene after exposure to a
      reductive atmosphere at 200  degrees C for 24 h. Compared to commercial Pt
      nanoparticle catalyst on Al2O3 and control samples, this system exhibits
      significantly enhanced stability and performance for n-hexane hydro-reforming at
      550  degrees C for 48 h, although agglomeration of Pt single-atoms into clusters
      is observed after reaction. In CO oxidation, the Pt single-atom identity was
      fully maintained after 60 cycles between 100 and 400  degrees C over a one-month
      period.

PMID- 28748957
TI  - Management of cardiovascular diseases in patients with obesity.
AB  - The management of cardiovascular diseases (CVD) in patients with obesity presents
      numerous challenges. Obesity has a negative effect on almost all of the major CVD
      risk factors, and adversely influences cardiovascular structure and function.
      Patients who are overweight or obese have a higher incidence of almost all CVDs
      compared with patients who are of normal weight. However, those who are
      overweight or obese seem to have a better short-term and medium-term prognosis
      after major CVD events and interventional procedures or cardiac surgeries than
      leaner patients, a phenomenon termed the 'obesity paradox'. In considering the
      mechanisms underlying this paradox, we review evidence of the deleterious
      consequences of obesity in patients with coronary heart disease, and the limited
      data on the benefits of weight loss in patients with CVD. Additional studies are
      needed on the efficacy of purposeful weight loss on cardiovascular outcomes to
      determine the ideal body composition for patients with CVD.

PMID- 28748959
TI  - Biological labels: Here comes the spaser.

PMID- 28748960
TI  - Acoustic metamaterials: Living bandgaps.

PMID- 28748961
TI  - Material witness: Seeking comfort in the Iron Age.

PMID- 28748962
TI  - Thermal hall effect: Turn your phonon.

PMID- 28748963
TI  - Maraging steels: Making steel strong and cheap.

PMID- 28748964
TI  - Molecular separation: Flexing with the flow.

PMID- 28748958
TI  - New and revisited approaches to preserving the reperfused myocardium.
AB  - Early coronary artery reperfusion improves outcomes for patients with ST-segment
      elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI
      remain unacceptably high. The primary deficits seen in these patients include
      inadequate pump function, owing to rapid infarction of muscle in the first few
      hours of treatment, and adverse remodelling of the heart in the months that
      follow. Given that attempts to further reduce myocardial infarct size beyond
      early reperfusion in clinical trials have so far been disappointing, effective
      therapies are still needed to protect the reperfused myocardium. In this Review,
      we discuss several approaches to preserving the reperfused heart, such as
      therapies that target the mechanisms involved in mitochondrial bioenergetics,
      pyroptosis, and autophagy, as well as treatments that harness the
      cardioprotective properties of inhaled anaesthetic agents. We also discuss
      potential therapies focused on correcting the no-reflow phenomenon and its effect
      on healing and adverse left ventricular remodelling.

PMID- 28748965
TI  - Corrigendum: Observation and coherent control of interface-induced electronic
      resonances in a field-effect transistor.

PMID- 28748966
TI  - En Marche!

PMID- 28748967
TI  - Melanocytic nevi and non-neoplastic hyperpigmentations.
AB  - This is the first of three chapters that will be progressively published on
      Pathologica as updating activity of the Italian Study Group of Dermatopathology
      (GISD), Italian Society of Pathology and Cytology (SIAPeC IAP). The first chapter
      concerns non-neoplastic hyperpigmented skin lesions and nevi, the second will
      address the topics of dysplastic nevus, borderline and low malignant potential
      melanocytic proliferations and the third melanoma in its variants and
      differential diagnoses with a supplement on the immunohistochemistry and
      molecular support to diagnostic and prognostic definition of nevi and melanomas.
      Although we believe that great advances were made in the application of ancillary
      genetic, immunohistochemical and molecular techniques, for the diagnosis and
      biological characterization of melanocytic tumors the morphology still remains
      the gold standard. These chapters are not intended as substitutes or even claim
      to be compared to the numerous and valuable texts that are also recently
      published, but they want to present, concisely and quickly available, all of
      those traits that we believe essential to the histopathological evaluation of a
      melanocytic lesion. No morphological parameter is exclusive and individually
      sufficient to make the correct diagnosis of nevus or melanoma but to reach a
      final conclusive and appropriate interpretation a set of morphological characters
      must be evaluated and compared. I was lucky enough to be able to examine several
      thousand cases and to draw lessons from each of these increasing my diagnostic
      experience. I had a great lesson by my teacher and good friend Prof. Martin C.
      Mihm Jr of Boston, dermato-pathologist with undisputed international reputation,
      who, with great passion, patience and friendship, transferred me much of his
      experience and knowledge and for which I always thank him. Special thanks I would
      like to address Dr. Agostino Crupi, dermatologist, skin-oncologist and brilliant
      dermatoscopist who taught me how the diagnosis of melanocytic lesions starts from
      the clinic examination and the mutual comparison between dermatologist and
      pathologist is a great richness of knowledge for both. Finally thank to my
      collaborators Barbara Rubino, Barbara Bruni and Antonella Festa for the large
      number of material collected in these years at the Pathology Service of the IRCCS
      Policlinico San Donato and a particular thank to Marco Turina who collaborated in
      the drafting of this text.

PMID- 28748968
TI  - Drug-induced gastrointestinal injury (DIGI). Updates, reflections and key points.
AB  - The goals of this short narrative review are 1) to provide an update in recent
      developments in the field of drug-induced gastrointestinal injury (DIGI), and 2)
      to distill few key points to approach with confidence a difficult and vast area
      of gastrointestinal pathology. DIGI is a challenging diagnosis as it can produce
      almost any pattern of the injury of the gastrointestinal tract. The recognition
      of a pattern and the knowledge of which drugs can produce that pattern, are the
      first step of the diagnostic process; communication with the clinical team and a
      high level of suspicion are then paramount. The pathologist can be the leading
      clinicians of the care team in few situations in which she/he can recognize the
      drug at the microscope. Knowledge of the most relevant differential diagnoses of
      DIGI is essential to avoid significant pitfalls. Finally, several DIGIs due to
      recently developed immunomodulators used in oncology have shown relevance given
      their sometimes fatal outcome and the accumulating evidence of a common
      morphological appearance among them.

PMID- 28748969
TI  - Discovering intratumor heterogeneity: the next frontier for pathologists.
AB  - Discovering intratumor heterogeneity is a crucial issue in modern oncologic
      medicine. Highly sophisticated technology such as high-throughput DNA sequencing
      has demonstrated the real dimension of the problem. The overwhelming majority of
      malignant tumors show high levels of intratumor heterogeneity when thoroughly
      studied. Intratumor heterogeneity develops both in temporal and spatial domains
      and its distribution is not deterministic making each case truly unique and
      unrepeatable. Pathologists are main actors in intratumor heterogeneity detection
      since they are the medical specialists who sample the tumors. Recent evidences
      have shown that currently applied sampling protocols are insufficient for a
      reliable intratumor heterogeneity detection. Pathologists must adapt classic
      sampling to the new times thus continuing being key pieces in the
      multidisciplinary approach to neoplasia that modern medicine demands.

PMID- 28748970
TI  - Lane's type pseudosarcoma of glans penis.
AB  - We herein present a rare case of polypoid "pseudosarcomatous lesion" of the glans
      penis, associated with in situ or mini-invasive squamous carcinoma. These
      lesions, described by Lane, in the upper aerodigestive tract, can rarely occur
      elsewhere. Immunohistochemistry is crucial for a correct diagnostic
      interpretation, confirming that the aytpical cells are components (fibroblasts,
      myofibroblasts, endothelial) of granulation tissue.

PMID- 28748971
TI  - Follicular dendritic cell sarcoma of the head and neck. Literature review and
      report of the tonsil occurrence in a Ugandan patient.
AB  - We report a case of follicular dendritic cell sarcoma (FDCS) in a 60-year-old
      Ugandan female who presented with a 6-year history of a progressive left sided
      tonsillary mass. General systemic examination was unrevealing and the patient
      underwent left tonsillectomy. She was subsequently lost to follow-up. Grossly,
      the mass measured 6 cm in diameter and had a mottled appearance due to tissue
      microhaemorrhages. Markers specific for follicular dendritic cell differentiation
      (CD21, CD35 and CD23), p53 and EGFR were expressed on immunohistochemical
      analysis. Review of all of the 49 published reports of tonsil FDCS showed that
      this entity tended to occur at younger age (mean: 44.5 yrs) in women than in men
      (mean: 49.4 yrs). Tumour size ranged from 0.8 to 5 cm in maximum dimension (mean
      2.9 cm). Only 12.2% of the patients presented with metastatic disease at initial
      diagnosis, all localised in the cervical lymph nodes. Local or distant
      recurrences occurred after a mean period of 72.5 months. In conclusion, although
      the pertinent literature suggests that FDCS should be considered at least of
      intermediate grade, our review indicates that FDCS of the tonsil region behaves
      as a low-grade sarcoma.

PMID- 28748972
TI  - Is it possible to determine the origin of cyst in empty thyroid bed in patient
      with lingual thyroid?
AB  - Some patients with ectopic thyroid gland or athyreotic patients have one or more
      cysts in empty thyroid bed. The origin of these cysts is uncertain. We present
      the patient with lingual thyroid gland and small cyst in empty thyroid bed
      featuring the diagnostic algorithm used and discussing the possible etiologic
      scenarios.

PMID- 28748973
TI  - RIORGANIZZAZIONE TERRITORIALE DEI LABORATORI DI ANATOMIA PATOLOGICA: PRO E
      CONTRO.

PMID- 28748974
TI  - Cranberries improve postprandial glucose excursions in type 2 diabetes.
AB  - Recent research supports a favorable role of cranberries on cardiometabolic
      health. Postprandial metabolism, especially hyperglycemia, has been shown to be
      an independent cardiovascular risk and few clinical studies have reported the
      role of berries in improving postprandial dysmetabolism. We investigated the
      postprandial effects of dried cranberries following a high-fat breakfast
      challenge in obese participants with type 2 diabetes (T2DM), in a randomized
      crossover trial. Blood draw and vascular measurements were conducted at fasting,
      1, 2 and 4 hours (h), following the consumption of a fast-food style high-fat
      breakfast (70 g fat, 974 kcal) with or without cranberries (40 g). Analyses of
      our data (n = 25; BMI (kg m-2) (mean +/- s.d.) = 39.5 +/- 6.5; age (years) = 56
      +/- 6) revealed that postprandial increases in glucose were significantly lower
      in the cranberry vs. control at 2 & 4 h (p < 0.05). No significant differences
      were noted in insulin, insulin resistance evaluated by homeostasis model
      assessment, lipid profiles and blood pressure between the cranberry and control
      groups. Among the biomarkers of inflammation and oxidation, postprandial serum
      interleukin-18 and malondialdehyde were significantly lower at 4 h, and serum
      total nitrite was higher at 2 h in the cranberry vs. control group (all p <
      0.05). No effects were noted on C-reactive protein or interlukin-6. Overall,
      dietary cranberries had notable effects in improving high-fat breakfast induced
      postprandial glucose and selected biomarkers of inflammation and oxidation in
      participants with T2DM. These findings provide evidence that adding whole
      cranberries to a high-fat meal may improve postprandial blood glucose management
      and warrant further investigation.

PMID- 28748975
TI  - Correction: Ultra-low fouling alkylimidazolium modified surfaces for the
      detection of HER2 in breast cancer cell lysates.
AB  - Correction for 'Ultra-low fouling methylimidazolium modified surfaces for the
      detection of HER2 in breast cancer cell lysates' by Alexandra Aube et al.,
      Analyst, 2017, 142, 2343-2353.

PMID- 28748976
TI  - Syntheses, structures and magnetic properties of the lanthanide complexes of the
      pyrimidyl-substituted nitronyl nitroxide radical.
AB  - Four 2p-4f LnIII-radical complexes, [(NIT-2-Pm)Ln(hfac)3].0.5C7H16 (NIT-2-Pm = 2
      pyrimidyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxy-3-oxide, hfac =
      hexafluoroacetylacetonato, Ln = Tb (1), Dy (2), Ho (3) and Er (4)), and four 4f
      2p-4f LnIII-radical-LnIII complexes, [(MU-NIT-2-Pm)Ln2(hfac)6(H2O)2].0.5C7H16 (Ln
      = Tb (5), Dy (6), Ho (7) and Er (8)) have been synthesized and characterized
      structurally and magnetically. These compounds can be selectively obtained by
      controlling the reaction ratio of Ln(hfac)3.2H2O to the radical ligand NIT-2-Pm.
      The crystal structures show that in the former four complexes 1-4, the NIT-2-Pm
      radical acts as a terminal bidentate ligand chelating to one LnIII ion, while in
      5-8, the NIT-2-Pm acts as a bridging ligand linking two LnIII ions to form a
      binuclear three-spin system. Magnetic studies revealed that complexes 1-4 and 6
      show frequency-dependent ac magnetic susceptibilities, suggesting a possible
      single-molecule magnet behavior. To the best of our knowledge, complexes 3 and 4
      are the first Ho-NIT and Er-NIT compounds showing slow magnetic relaxation.
      Compounds 5-8 represent a rare family of compounds showing the NIT bridged 4f-2p
      4f three-spin motif, while complex 6 is a rare NIT bridged multinuclear
      lanthanide compound possessing SMM-like behaviour. Ab initio calculations were
      performed on all these complexes. The fitting of the magnetic susceptibilities of
      these compounds suggests weak antiferromagnetic coupling between the LnIII and
      NIT radical in 1-8 and weak ferromagnetic LnIII-LnIII interactions in 5-8.

PMID- 28748977
TI  - Solvent-dependent photo-induced dynamics in a non-rigidly linked zinc
      phthalocyanine-perylenediimide dyad probed using ultrafast spectroscopy.
AB  - In this work, we characterize the energy and electron transfer kinetics of a zinc
      phthalocyanine-perylenediimide dyad (ZnPc-PDI) in various solvents using steady
      state and tunable narrowband pump-probe spectroscopy. We fit the ultrafast data
      with global analysis techniques and find that upon excitation of the PDI moiety
      (pump pulse at 540 nm), the excitation energy transfer (EET) rate to the ZnPc
      moiety displays a solvent sensitivity that we attribute to changes in the
      relative equilibrium moiety orientation. We rationalize these observations by
      considering the nature of the non-rigid bridge used to link the two moieties as
      well as the degenerate nature of the Q band transitions in the ZnPc species. By
      tuning the pulse into resonance with the ZnPc Q band (685 nm) we can directly
      photo-induce an electron transfer (ET) process back to the PDI moiety. Employing
      the same global analysis, we find that the dynamics of the ultrafast electron
      transfer are completely kinetically controlled according to the Bixon-Jortner
      model of barrierless solvent-controlled curve crossing, while the recombination
      to reform the ground state is well-described using the static energetic picture
      according to Marcus theory.

PMID- 28748978
TI  - Degradable polyesters via ring-opening polymerization of functional
      valerolactones for efficient gene delivery.
AB  - Degradable polymers as gene and drug carriers are emerging as one of the most
      promising types of materials in the biomedical and pharmaceutical areas. Herein,
      we report the synthesis of a series of block co-polyesters (B1-B6) and random co
      polyesters (C1-C4) via ring-opening polymerization of tertiary amine-bearing
      valerolactone and alkylated valerolactone monomers. These polymers can completely
      inhibit the electrophoretic migrations of plasmid DNAs (pDNAs) at a w/w ratio of
      2-6. The polyplexes of these polymers with pDNAs were steadily formed in a narrow
      range of sizes (75 to 220 nm) and could be effectively internalized into the
      cytoplasm. The results of transfection experiments showed that the block
      copolymers generally exhibited better performance than their random counterparts
      and the aliphatic chain lengths on the backbone of the polymers obviously
      affected the transfection efficiency (TE). Block copolymer B5 with n-octyl chains
      generated the best TE in Hek293T cells, which was 2.2 fold that of
      polyethylenimine (PEI) 25k under the optimal conditions. Moreover, these polymers
      were found to be more biocompatible compared to PEI 25k, and showed degradable
      properties. Our results suggest that these polymers are potentially
      reliable/efficient non-viral gene vectors.

PMID- 28748979
TI  - Detection of the anticoagulant drug warfarin by palladium complexes.
AB  - Warfarin, a commercial anticoagulant drug, is extensively used to prevent blood
      clots in the blood vessel but lack of adequate analytical techniques poses
      serious monitoring issues. This work illustrates the application of Pd(ii)
      complexes not only in the excellent sensing of warfarin in organic but also in
      aqueous medium.

PMID- 28748980
TI  - Investigation on the function of nonionic surfactants during compressed CO2
      mediated periodic mesoporous organosilica formation.
AB  - A systematic study on the structural properties and component information of
      periodic mesoporous organosilicas synthesized by using different nonionic
      surfactants as templates with compressed CO2 was carried out. Triblock copolymers
      (F127, F108, and P123), oligomeric alkyl poly(ethylene oxide) (Brij-58 and Brij
      76), and alkyl-phenol poly(ethylene oxide) (TX-100) have been employed as
      templates and BTEB as a bridged organosilica precursor to synthesize PMO
      materials at 5.90 MPa. The structure and morphology of the obtained materials
      were investigated by means of transmission electron microscopy (TEM), nitrogen
      sorption isotherms, solid Si and C NMR, and FTIR. Efforts have also been made to
      compare the differences in structural and morphological properties among these
      samples synthesized under similar conditions. We also investigate the synthesis
      of PMOs using F127 as the template at different CO2 pressures. It was found that
      the interaction between different organic silica precursors and surfactants with
      a variety of hydrophilic and hydrophobic chains is the key factor for the
      disorder degree of mesostructures. On this basis, the possible mechanism of
      formation of PMOs synthesized using a nonionic surfactant (triblock copolymer) as
      the template with compressed CO2 is illustrated and discussed.

PMID- 28748981
TI  - Terminal vs. bridging coordination of CO and NO ligands after decarbonylation of
      [W2Cp2(MU-PR2)(CO)3(NO)] complexes (R = Ph, Cy). An experimental and
      computational study.
AB  - Compounds [M2Cp2(MU-PPh2)(CO)3(NO)] (M = Mo, W) were prepared by reacting the
      corresponding radicals [M2Cp2(MU-PPh2)(CO)4] with NO, and displayed a terminal,
      linear NO ligand arranged cis to the P-donor ligand (Mo-Mo = 3.1400(7) A). The
      related PCy2-bridged complex [W2Cp2(MU-PCy2)(CO)3(NO)] was prepared in a one-pot,
      three step procedure first involving deprotonation of the hydride complex
      [W2Cp2(MU-H)(MU-PCy2)(CO)4] with K[BH(sec-Bu)3], then oxidation of the resulting
      salt K[W2Cp2(MU-PCy2)(CO)4] with [FeCp2]BF4 at 243 K, and eventually by reacting
      the so-formed radical [W2Cp2(MU-PCy2)(CO)4] with NO. Photochemical
      decarbonylation of the Mo2 complex gave intractable mixtures of products. In
      contrast, photolysis of the ditungsten complexes yielded the corresponding
      dicarbonyls [W2Cp2(MU-PR2)(MU-kappa1:eta2-CO)(CO)(NO)] (R = Ph, Cy) as major
      products, which were characterized spectroscopically. The latter reacted readily
      with P(OMe)3 to give the corresponding derivatives [W2Cp2(MU
      PR2)(CO)2(NO){P(OMe)3}], displaying a cisoid conformation of the P-donor ligands
      (P-W-P = 83.7(1) degrees  when R = Cy). Density functional theory calculations on
      [W2Cp2(MU-PCy2)(MU-kappa1:eta2-CO)(CO)(NO)] and several potential isomers
      revealed that this electron-precise molecule (W-W = 3.121 A) is almost
      isoenergetic with an unsaturated isomer having a MU-kappa1:kappa1-NO ligand (W-W
      = 2.677 A) but their interconversion has a large kinetic barrier. It was
      concluded that formation of the kappa1:eta2-CO-bridged isomers in the photolytic
      experiment is favoured by the cisoid disposition of NO and PR2 ligands at the
      parent tricarbonyls, which precludes the NO ligand from easily rearranging into a
      bridging position after decarbonylation. The above calculations also revealed
      that the CO ligand is much better suited than NO for the MU-kappa1:eta2
      coordination mode, since it can establish stronger end-on and side-on
      interactions with the dimetal centre.

PMID- 28748982
TI  - The model of Institut Catala de Salut for Prison Healthcare.

PMID- 28748983
TI  - Design, Planning and Management of the Hospital Custody Unit at Hospital
      Universitario Fundacion Alcorcon.
AB  - OBJECTIVE: The design and management of a Hospital Custody Unit at Hospital
      Universitario Fundacion Alcorcon, to focus the aim of this study on specialized
      medical care for extra-penitentiary patients who have suffered from a disease. We
      are building a new space to facilitate their daily lives at hospital and we want
      to offer a double function to the patients that consists of a custody space and a
      health rehabilitation space. MATERIAL AND METHODS: We carried out a scientific
      literature search on the international and national databases, about Hospital
      Custody Units or Restricted Access Units. The language of the reviews that we
      checked was English and Spanish. RESULTS: We wrote the Action Guide of the
      Hospital Custody Unit for the design, planning and management of the Hospital
      Custody Unit at Hospital Universitario Fundacion Alcorcon. (We included
      complementary bibliographic material and the Quick Guide in the Unit).
      DISCUSSION: The Hospital Custody Unit will be compatible with medical activity,
      occupational safety and the custody of patients that are in prison. We thus
      require consensus with police departments about custody protocols along with
      assistance from the clinicians' teams at penitentiary centers and referral
      hospitals. Furthermore, it is important to step up special care for mental health
      and to promote telemedicine and new technologies to streamline medical care along
      with coordination with healthcare professionals.

PMID- 28748984
TI  - Deaths from acute drug reactions in Galician (Spain) Prisons (2001-2010).
AB  - INTRODUCTION AND OBJECTIVES: drug use is associated with multiple complications
      with an increase in morbidity, with death by acute drugs reactions (ADR) being
      the most serious. A large percentage of the prison population has problems
      associated with drug additions, and substance abuse is also a common internal
      problem of penal institutions, despite their control measures. The goal of this
      study is to analyse the prevalence of ADR in penitentiaries, deceased
      sociodemographic characteristics as well as the circumstances in which they are
      produced. MATERIAL AND METHODS: All deaths by ADR between 2001-2010 in Galicia
      are studied, in particular, those deaths that took place inside prisons. RESULTS:
      In the whole sample (n=510) male (90.6%), single (46.1%) with an average age of
      35.8 and with a prevalent factor of long experience in drug abuse. Thirty seven
      of them died in Penal/Correctional Institutions, representing 7.3% of the total
      sample. The characteristics of this population subtype were similar to the total
      sample (average age: 34.7 years; 89.2% were males) but we found significant
      differences regarding the substances detected. DISCUSSION: ADR is the most
      frequent cause of death among drug addict convicts in prisons. The pattern of the
      detected substances in the toxicological analysis as well as the socio
      demographic characteristics can help to establish a higher risk profile and
      preventive measures.

PMID- 28748985
TI  - Brief update on diabetes for general practitioners.
AB  - Diabetes includes a group of metabolic disorders in which there is hyperglycemia.
      This can be due to impaired insulin secretion, insulin action or both. Chronic
      hyperglycemia is associated with serious long-term complications in several
      organs, especially in the eyes, kidneys, nerves, heart and blood vessels. In our
      country this disorder affects 13.8% of the population. There are several types of
      diabetes although most patients suffer type 2 diabetes. We set out to review the
      diagnostic process, screening recommendations, prevention strategies, initial
      assessment upon diagnosis, therapeutic targets regarding both blood glucose
      levels and the other vascular risk factors while also considering healthy
      lifestyles and brief references to medications recommended in each section.

PMID- 28748986
TI  - Chronic acromioclavicular dislocation and torture allegations in detention.

PMID- 28748987
TI  - Opioids in prison: can we reduce their use?

PMID- 28748988
TI  - [Characterization of patients with sporadic colorectal cancer following the new
      Consensus Molecular Subtypes (CMS)].
AB  - BACKGROUND: Colorectal cancer (CRC) is an heterogeneous disease. Three
      carcinogenic pathways determine its molecular profile: microsatellite instability
      (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP).
      Based on the new molecular classification, four consensus CRC molecular subtypes
      (CMS) are established, which are related to clinical, pathological and biological
      characteristics of the tumor. AIM: To classify Chilean patients with sporadic CRC
      according to the new consensus molecular subtypes of carcinogenic pathways.
      MATERIAL AND METHODS: Prospective analytical study of 53 patients with a mean age
      of 70 years (55% males) with CRC, operated at a private clinic, without
      neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI
      and CIMP were analyzed. Combining these variables, tumors were classified as
      CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal. RESULTS:
      CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR
      complex deficiencies and 67% had an activating mutation of the BRAF oncogene.
      CMS2 tumors (31%) were located in the left colon, had moderate differentiation,
      absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also
      left-sided, with absence of vascular and lymphatic invasion, and 29% had an
      activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced
      stages and presence of metastases. CONCLUSIONS: This new molecular classification
      contributes to understanding the heterogeneity of tumors. It is possible to
      differentiate molecular subgroups of a single pathological diagnosis of
      adenocarcinoma, opening the door to personalized medicine.

PMID- 28748989
TI  - [Association of abo blood groups with gestational diabetes mellitus].
AB  - BACKGROUND: ABO and Rhesus blood systems are associated with type 2 Diabetes
      Mellitus (DM2). Gestational Diabetes (GDM) is a model to study DM. AIM: To study
      the association between GDM and ABO and Rhesus groups. MATERIAL AND METHODS: A
      retrospective cohort study was performed in 1,078 women who gave birth to a
      singleton in Talca Regional Hospital, Chile, during 2008. We analyzed personal,
      obstetric, medical data and ABO and Rh blood groups. RESULTS: GDM was diagnosed
      in 6.6% of women. Age and body mass index were significantly associated with GDM.
      There were no differences in Rh blood groups (p = 0.604), while ABO groups were
      different between GDM and controls. B antigen was present in 3% of GDM women and
      in 10.8% of controls (p = 0.037), with an odds ratio of 0.25 after adjusting for
      other associated risk factors (p = 0.06). CONCLUSIONS: ABO group is suggested as
      a possible protector marker for GDM.

PMID- 28748991
TI  - [Analysis of incident reports in an anesthesiology unit of a university
      hospital].
AB  - BACKGROUND: Incident reporting is an effective strategy used to enhance patient
      safety. An incident is an event that could eventually result in harm to a
      patient. AIM: To classify and analyze incidents reported by an Anesthesiology
      division at a University hospital in Chile. MATERIAL AND METHODS: A retrospective
      analysis of the reported incidents registered in our institutional database from
      January 2008 to January 2014. They were classified according to three variables
      proposed by the World Health Organization system to determine the type of
      incident and patients? potential harm. RESULTS: There were 297 reports
      registered. Etiologic classification according to the WHO system showed that 29%
      (n = 85) were related with management, 20% (59) with drugs, 20% (59) with medical
      devices, 16% (48) with procedures and 15% (46) with human factors. Seventy two
      percent (58) of incidents caused low or moderate harm and 28% (22) resulted in a
      severe adverse event or death. CONCLUSIONS: Our analysis highlights that a high
      rate of incidents are associated with management, the leading cause of reports in
      our center. Due to the low incident report rate in our country, it is difficult
      to perform appropriate comparisons with other centers. In the future, local
      incident reporting systems should be improved.

PMID- 28748990
TI  - [Clinical features of patients with Basedow Graves disease seen at a university
      hospital].
AB  - BACKGROUND: Basedow Graves disease (BGD) is the leading cause of hyperthyroidism.
      The characteristics of patients seen at a university hospital may differ from
      those described in the general population. AIM: To describe the clinical features
      of patients with BGD seen at a university hospital. MATERIAL AND METHODS: Review
      of medical records of all patients seen at our hospital between 2009 and 2014
      with the diagnosis of thyrotoxicosis, hyperthyroidism or BGD. Clinical features,
      laboratory results and treatments were recorded. RESULTS: We reviewed clinical
      records of 272 patients; 15 had to be excluded due to incomplete data. BGD was
      present in 77.9% (n = 212). The mean age of the latter was 42 years (range 10-81)
      and 76% were women. Ninety six percent were hyperthyroid at diagnosis and thyroid
      stimulating hormone was below 0.1 mIU/L in all patients. Median free thyroxin and
      triiodothyronine levels were 3.26 ng/dl and 3.16 ng/ml, respectively. Thyrotropin
      receptor antibodies were positive in 98.5% and 85.7% had positive thyroid
      peroxidase antibodies. Graves orbitopathy (GO) was clinically present in 55% of
      patients. Of this group, 47% had an active GO, 26% had a moderate to severe
      disease and 7.8% had sight-threatening GO. As treatment, 26% received
      radioiodine, 44% anti-thyroid drugs exclusively, 28% underwent thyroidectomy and
      2% did not require therapy. CONCLUSIONS: In this group of patients, we observed a
      greater frequency of severe eye disease and a high rate of surgical management.
      This finding could be explained by referral to highly qualified surgical and
      ophthalmological teams.

PMID- 28748992
TI  - [Screening for malnutrition among hospitalized patients in a Colombian University
      Hospital].
AB  - BACKGROUND: On admission, 30 to 50% of hospitalized patients have some degree of
      malnutrition, which is associated with longer length of stay, higher rates of
      complications, mortality and greater costs. AIM: To determine the frequency of
      screening for risk of malnutrition in medical records and assess the usefulness
      of the Malnutrition Screening Tool (MST). MATERIAL AND METHODS: In a cross
      sectional study, we searched for malnutrition screening in medical records, and
      we applied the MST tool to hospitalized patients at the Internal Medicine Wards
      of San Ignacio University Hospital. RESULTS: Of 295 patients included, none had
      been screened for malnutrition since hospital admission. Sixty one percent were
      at nutritional risk, with a higher prevalence among patients with HIV (85.7%),
      cancer (77.5%) and pneumonia. A positive MST result was associated with a 3.2
      days increase in length of hospital stay (p = 0.024). CONCLUSIONS: The prevalence
      of malnutrition risk in hospitalized patients is high, but its screening is
      inadequate and it is underdiagnosed. The MST tool is simple, fast, low-cost, and
      has a good diagnostic performance.

PMID- 28748993
TI  - [Sedentary lifestyle is associated with metabolic and cardiovascular risk factors
      independent of physical activity].
AB  - BACKGROUND: Sedentary behavior is a main risk factor for cardiovascular disease
      and mortality. AIM: To investigate the association between sedentary behavior and
      metabolic and cardiovascular risk factors. MATERIAL AND METHODS: We assessed 322
      participants aged between 18 to 65 years. Physical activity and sedentary
      behavior were measured with accelerometers (Actigraph(r)). Body mass index (BMI),
      waist circumference, percentage of body fat, diet and blood markers (glucose,
      lipid profile, insulin and HOMA-IR) were measured with standardized protocols.
      RESULTS: Thirty four percent of participants were physically inactive and spent
      on average 8.7 h/day on sedentary activities. Per one hour increase in sedentary
      behavior there were significant adverse changes in glucose (4.79 mg/dl), insulin
      (2.73 pmol/l), HOMA-IR (0.75), BMI (0.69 kg/m2), waist circumference (1.95 cm),
      fat mass (1.03%), total cholesterol (9.73 mg/dl), HDL-cholesterol (-3.50 mg/dl),
      LDL-cholesterol (10.7 mg/dl) and triglycerides (12.4 mg/dl). These findings were
      independent of main confounding factors including total physical activity,
      dietary factors, BMI and socio-demographics. CONCLUSIONS: The detrimental effect
      of sedentary behaviors on cardiometabolic and obesity-related traits is
      independent of physical activity levels. Therefore, reducing sedentary time
      should be targeted in the population apart from increasing their physical
      activity levels.

PMID- 28748994
TI  - [Intravenous thrombolysis for acute ischemic stroke. A four years? experience in
      a Chilean public hospital].
AB  - BACKGROUND: Intravenous thrombolysis (IVT) with alteplase (tissue plasminogen
      activator) is the standard pharmacological treatment in acute ischemic stroke
      (AIS), reducing disability in patients. AIM: To report the results a thrombolysis
      protocol during four years in a regional public hospital. MATERIAL AND METHODS:
      Data from 106 consecutive patients aged 68 +/- 13 years (57% men) who were
      treated with IVT, from May 2012 until April 2016, was analyzed. RESULTS: The
      median door-to-needle time was 80 minutes (interquartile range = 57-113). The
      median National Institute of Health Stroke Scale (NIHSS) scores on admission and
      at discharge were was 11.5 and 5 points respectively. At discharge, 27% of
      hospitalized patients had a favorable outcome (n = 99), defined as having 0 to 1
      points in the modified Rankin scale. Symptomatic intracerebral hemorrhage and
      mortality rates were 5.7 and 13.1%, respectively. The thrombolysis rate rose from
      0.7% in 2012 to 6% in 2016. CONCLUSIONS: The implementation of 24/7 neurology
      shifts in the Emergency Department allowed us to increase the amount and quality
      of IVT in our hospital, as measured by the rate of thrombolysis and by process
      indicators such as door-to-needle time.

PMID- 28748995
TI  - [Effects of a mindfulness intervention in Chilean high schoolers].
AB  - BACKGROUND: Mindfulness has been conceptualized as paying attention to present
      moment experience in a non-judgmental manner, and the practice of developing that
      skill. AIM: To determine the impact of a mindfulness-based intervention on
      negative emotional states of anxiety, stress, and depression in Chilean high
      schoolers. MATERIAL AND METHODS: Eighty-eight teenagers aged 13 +/- 0.6 years (46
      females) were randomly assigned to a mindfulness group or a control (41 and 47,
      respectively). The mindfulness intervention consisted in eight weekly 45-minute
      sessions. A depression, anxiety, and stress scale (DASS-21) was applied at
      baseline, after the intervention, and at three and six-month follow-up. RESULTS:
      There was a significant reduction in anxiety, depression, and general
      symptomatology in the experimental group compared to the control group. However,
      these changes were not sustained at follow-up. CONCLUSIONS: These preliminary
      results suggest the feasibility and effectiveness of a mindfulness intervention
      in Chilean schools as a strategy to reduce negative emotional states and prevent
      risk factors in adolescent population groups.

PMID- 28748996
TI  - Clinical applications of pharmacogenomics.
AB  - Pharmacogenomics is an emergent field aimed at tailoring pharmacological therapy.
      Genetic polymorphisms can modify the expression and function of enzymes and
      proteins involved in drug metabolism, affecting absorption, distribution,
      biotransformation and excretion as well as the drug-target interaction.
      Therefore, the presence of allelic variants will classify people as poor,
      extensive or rapid/ultra rapid metabolizers, modifying drug efficacy and safety.
      In this work, the state of art in relation to this discipline is presented and
      the genetic variants of enzymes that are involved in drug pharmacokinetics or
      pharmacodynamics are described. The effects of these variants on the therapeutic
      response to drugs used in our country are also discussed.

PMID- 28748997
TI  - [Role of Mediterranean diet on the prevention of Alzheimer disease].
AB  - Type 2 diabetes and obesity are possible risk factors for Alzheimer?s disease and
      these can be modified by physical activity and changes in dietary patterns, such
      as switching to a Mediterranean diet. This diet includes fruits, vegetables,
      olive oil, fish and moderate wine intake. These foods provide vitamins,
      polyphenols and unsaturated fatty acids. This diet should be able to reduce
      oxidative stress. The inflammatory response is also reduced by unsaturated fatty
      acids, resulting in a lower expression and a lower production of pro-inflammatory
      cytokines. The Cardiovascular protection is related to the actions of polyphenols
      and unsaturated fatty acids on the vascular endothelium. The Mediterranean diet
      also can improve cardiovascular risk factors such as dyslipidemia, hypertension
      and metabolic syndrome. These beneficial effects of the Mediterranean diet should
      have a role in Alzheimer?s disease prevention.

PMID- 28748998
TI  - [Paul Cezanne, the lonely precursor of modern painting].
AB  - Paul Cezanne is an acknowledged pioneer of modern painting. His work was poorly
      recognized during most of his solitary life. He progressively withdrew from
      people and society during his life, in part due to his introverted personality
      and a supreme effort to obtain a unique form of expression of his art, in which
      nature and its inner secrets played a pivotal role. In this review, we discuss
      aspects of his life and art, his pathological personal relationships and how they
      influenced his transcendental work.

PMID- 28748999
TI  - [Simulation in medical education from the perspective of patients? safety].
AB  - We herein review the association between patients? safety and simulation methods
      for medical education. This evidence should help to change the present paradigm
      in medical education, where there is still reticence towards this education
      method. A total of 20 papers on the subject were reviewed. Ninety percent of
      these articles conclude that simulation contributes to patient safety, 5%
      conclude that the evidence is uncertain and 5% conclude that the effects will be
      seen in the next decade. Thus, the majority of papers support the use of
      simulation in medical education as a method that improves patients? safety.

PMID- 28749000
TI  - [Bone metastases of a gallbladder carcinoma detected by positron emission
      tomography/computed tomography: Case report].
AB  - Signet ring gallbladder carcinoma is a rare aggressive variant of mucinous
      adenocarcinoma with poor prognosis. Positron emission tomography/computed
      tomography (PET/CT) with Fluor18 deoxyglucose (F18-FDG) is a useful tool in the
      staging of gallbladder cancer. We report a 68 years old man with a surgically
      resected acute cholecystitis, whose biopsy was positive for signet ring cell
      gallbladder carcinoma. During surgery, locoregional lymph nodes, liver or
      peritoneal involvement were not detected. A PET/CT was performed for staging,
      finding multiple hypermetabolic lytic bone lesions. Percutaneous biopsy of a
      pelvis bone lesion, confirmed a metastasis of the tumor. In this case, the
      staging with PET/CT allowed the diagnosis of unsuspected bone metastases and was
      a useful tool for deciding the best site of biopsy for histologic confirmation.

PMID- 28749001
TI  - [Carney triad: Report of one case].
AB  - Carney described a disorder characterized by the presence of several uncommon
      tumors which were pulmonary chondromas, gastric sarcomas and extra-adrenal
      paragangliomas. We report a 14 year-old girl in whom multiple gastric tumors were
      discovered during a study of an iron deficiency anemia and was subjected to a
      partial gastrectomy. At 25 years of age, she developed several pulmonary
      chondromas and at 33 years, a mediastinal tumor with features of an extra-adrenal
      paraganglioma was found. At 35 years of age, a total gastrectomy was performed to
      remove a gastrointestinal stromal tumor with excision of peritoneal and lymph
      node metastasis. One year later, the patient died due to liver failure secondary
      to liver metastases.

PMID- 28749002
TI  - [Natalizumab for the treatment of Crohn?s disease: Report of three cases].
AB  - Anti-tumor necrosis factor-alpha (TNF) agents have dramatically changed the
      management of Crohn?s Disease (CD). However, a significant number of these
      patients do not respond at all or cease to respond to antibodies against TNF. In
      this clinical situation, the options include intensification of anti-TNF therapy
      by either increasing the dose or by shortening the administration interval, the
      use of a second anti-TNF or medications with a different mechanism of action.
      Among the later, Natalizumab, a humanized IgG4 monoclonal antibody against
      alpha4beta1 and alpha4beta7 integrins, is safe and effective in inducing and
      maintaining remission in active CD patient?s refractory to anti-TNF. In spite of
      this, Natalizumab use has been limited because of an increased risk of
      progressive multifocal leukoencephalophaty which results from reactivation of the
      John Cunningham (JC) virus. However, the presence of antibodies against JC virus
      in serum can be used to reduce the risk for this complication. We report three
      patients with Crohn?s disease refractory to treatment with infliximab, who
      responded successfully to the use of Natalizumab.

PMID- 28749003
TI  - [Bilateral spontaneous renal pelvis rupture during a computed tomography: Report
      of one case].
AB  - Spontaneous rupture of the urinary excretory system is a rare condition. It is
      mainly associated with obstruction of the excretory system and is usually
      unilateral. We report a 58 years old male who, during the performance of a
      computed tomography of the urinary system, felt an intense lumbar pain. A
      bilateral rupture at the level of the fornix was found. The patient had an
      uneventful evolution thereafter. Fifteen days later a new computed tomography
      showed indemnity of the urinary excretory system.

PMID- 28749004
TI  - [Linking scientific research with undergraduate training in health science
      related majors].

PMID- 28749005
TI  - Screening of furanocoumarin derivatives as cytochrome P450 3A4 inhibitors in
      citrus.
AB  - WHAT IS KNOWN AND OBJECTIVE: Furanocoumarins, such as bergamottin (BG) and 6',7'
      dihydroxybergamottin (DHB), isolated from grapefruit juice are clinically active
      constituents capable of inhibiting cytochrome P450 3A4. Furanocoumarins are also
      found in hassaku, pummelo and daidai. Several types of hybrid citrus fruits have
      recently been developed, and these may also contain furanocoumarins because they
      were produced by cross-breeding pummelo, daidai and other citrus fruits. In this
      study, we quantified BG and DHB levels in the flesh and peel of hybrid citrus
      fruits. METHODS: Extracts from flesh and peel were diluted with acetonitrile and
      analysed using high-performance liquid chromatography. RESULTS AND DISCUSSION:
      For flesh extracts, lime juice (24.13 MUg/mL) contained a greater amount of BG
      than grapefruit juice (13.61 MUg/mL). Lime (13.21 MUg/mL) and sour orange (8.08
      MUg/mL) juices also contained greater amounts of DHB than grapefruit juice (7.54
      MUg/mL). For peel extracts, lime (1749.15 MUg/g), Citrus kawachibankan (308.13
      MUg/g), lemon (203.44 MUg/g) and sour orange (161.95 MUg/g) contained greater
      amounts of BG than grapefruit (white) (78.80 MUg/g). The hybrid sweetie (Citrus
      maxima * Citrus paradise; 173.32 MUg/g) contained a greater amount of DHB than
      grapefruit (white) (85.27 MUg/g). WHAT IS NEW AND CONCLUSION: The lime flesh and
      the sweetie peel contained the greatest amounts of furanocoumarins. Thus, caution
      is required during the simultaneous use of drugs metabolized by cytochrome P450
      3A4 and consumption of these citrus fruits.

PMID- 28749006
TI  - Highly cis-1,4 Selective Living Polymerization of Unmasked Polar 2-(2
      Methylidenebut-3-enyl)Furan and Diels-Alder Addition.
AB  - The polymerization of a new polar diene-based monomer 2-(2-methylidenebut-3
      enyl)furan (MBEF) without masking is achieved by using the
      bis(phosphino)carbazoleide-ligated yttrium (Y) alkyl complex upon the activation
      of [Ph3 C][B(C6 F5 )4 ]. Under mild conditions, the polymerizations under the
      monomer-to-Y ratios ranging from 100:1 to 500:1 perform fluently in high yields.
      The afforded polydienes bearing pendant terminal furan groups have high cis-1,4
      regularity up to 98.6% and molecular weights close to the theoretic values and
      narrow polymer dispersity index(PDI) (1.13-1.17) suggesting a livingness
      polymerization mode. In addition, this novel polydiene is an excellent building
      block for preparing functional rubber materials. For example, via Diels-Alder
      addition of furan groups under mild conditions, hydroxyl groups are successfully
      introduced on the side chains efficiently in a 75% conversion. Furthermore, the
      copolymerization of polar MBEF and nonpolar isoprene is also successfully
      realized by the bis(phosphino) carbazoleide-ligated scandium analog to access
      furan-modified cis-1,4 (>97%) polyisoprene with different MBEF contents (5.3%,
      8.7%).

PMID- 28749007
TI  - Reactive oxygen species as mediators of sperm capacitation and pathological
      damage.
AB  - Oxidative stress plays a major role in the life and death of mammalian
      spermatozoa. These gametes are professional generators of reactive oxygen species
      (ROS), which appear to derive from three potential sources: sperm mitochondria,
      cytosolic L-amino acid oxidases, and plasma membrane Nicotinamide adenine
      dinucleotide phosphate oxidases. The oxidative stress created via these sources
      appears to play a significant role in driving the physiological changes
      associated with sperm capacitation through the stimulation of a cyclic adenosine
      monophosphate/Protein kinase A phosphorylation cascade, including the activation
      of Extracellular signal regulated kinase-like proteins, massive up-regulation of
      tyrosine phosphorylation in the sperm tail, as well as the induction of sterol
      oxidation. When generated in excess, however, ROS can induce lipid peroxidation
      that, in turn, disrupts membrane characteristics that are critical for the
      maintenance of sperm function, including the capacity to fertilize an egg.
      Furthermore, the lipid aldehydes generated as a consequence of lipid peroxidation
      bind to proteins in the mitochondrial electron transport chain, triggering yet
      more ROS generation in a self-perpetuating cycle. The high levels of oxidative
      stress created as a result of this process ultimately damage the DNA in the sperm
      nucleus; indeed, DNA damage in the male germ line appears to be predominantly
      induced oxidatively, reflecting the vulnerability of these cells to such stress.
      Extensive evaluation of antioxidants that protect the spermatozoa against
      oxidative stress while permitting the normal reduction-oxidation regulation of
      sperm capacitation is therefore currently being undertaken, and has already
      proven efficacious in animal models.

PMID- 28749009
TI  - The Origin of Hierarchical Structure Formation in Highly Grafted Symmetric
      Supramolecular Double-Comb Diblock Copolymers.
AB  - Involving supramolecular chemistry in self-assembling block copolymer systems
      enables design of complex macromolecular architectures that, in turn, could lead
      to complex phase behavior. It is an elegant route, as complicated and sensitive
      synthesis techniques can be avoided. Highly grafted double-comb diblock
      copolymers based on symmetric double hydrogen bond accepting poly(4
      vinylpyridine)-block-poly(N-acryloylpiperidine) diblock copolymers and donating 3
      nonadecylphenol amphiphiles are realized and studied systematically by changing
      the molecular weight of the copolymer. Double perpendicular lamellae-in-lamellae
      are formed in all complexes, independent of the copolymer molecular weight.
      Temperature-resolved measurements demonstrate that the supramolecular nature and
      ability to crystallize are responsible for the formation of such multiblock-like
      structures. Because of these driving forces and severe plasticization of the
      complexes in the liquid crystalline state, this supramolecular approach can be
      useful for steering self-assembly of both low- and high-molecular-weight block
      copolymer systems.

PMID- 28749008
TI  - Propofol post-conditioning alleviates hepatic ischaemia reperfusion injury via
      BRG1-mediated Nrf2/HO-1 transcriptional activation in human and mice.
AB  - To explore the effects of propofol post-conditioning (PPC) on hepatic
      ischaemia/reperfusion injury (HIRI) and the potential mechanisms that might be
      involved in the interaction of Brahma-related gene1(BRG1) and Nuclear-related
      factor 2(Nrf2). Patients were randomized into PPC(n = 16) and non-PPC(NPC)( n =
      21) groups. Propofol(2 mg/kg) was infused within 10 min. of the onset of liver
      reperfusion during liver transplantation in the PPC group. Liver function tests,
      as well as Brg1, Nrf2, Heme oxygenase-1(HO-1) and NADPH:quinone
      oxidoreductase1(NQO1) expression levels were evaluated. CMV-Brg1 mice were
      designed to investigate the role of Brg1 overexpression during HIRI. Brg1 and
      Nrf2 siRNA were used to examine the relationship between Brg1 and Nrf2/HO-1
      pathways in propofol-mediated effects in a human hepatocyte(L02)
      hypoxia/reoxygenation(H/R) model. In patients, PPC attenuated both donor liver
      pathological and function injury, and reducing oxidative stress markers, compared
      to the NPC group, 24 hrs after surgery. PPC increased liver Brg1, Nrf2, HO-1 and
      NQO1 expression. In mice, PPC reduced HIRI by decreasing liver oxidative stress
      and activating Nrf2/HO-1 pathway, accompanied by up-regulation of BRG1
      expression. BRG1 overexpression activated Nrf2/HO-1 transcription in CMV-BRG1
      mice during HIRI. In vitro, PPC significantly elevated expression of Nrf2, HO-1
      and NQO1, resulting in a reduction of cell DCFH-DA and 8-isoprostane levels and
      decreased lactate dehydrogenase levels, leading to an overall increase in cell
      viability. Moreover, the protective effects of propofol were partially abrogated
      in Nrf2-knock-down or BRG1-knock-down hepatocytes. Nrf2-knock-down drastically
      reduced protein expression of HO-1 and NQO1, while Brg1-knock-down decreased HO-1
      expression. Propofol post-conditioning alleviates HIRI through BRG1-mediated
      Nrf2/HO-1 transcriptional activation.

PMID- 28749010
TI  - Radiofrequency ablation of fast ventricular tachycardia causing an ICD storm in
      an infant with hypertrophic cardiomyopathy.
AB  - An implantable cardioverter defibrillator (ICD) storm involves very frequent
      arrhythmia episodes and ICD shocks, and it is associated with poor short-term and
      long-term prognosis. Radiofrequency catheter ablation can be used as an effective
      rescue treatment for patients with an ICD storm. To our knowledge, this is the
      first report of an infant with hypertrophic cardiomyopathy presenting with an ICD
      storm and undergoing successful radiofrequency catheter ablation salvage
      treatment for the fast left posterior fascicular ventricular tachycardia.

PMID- 28749011
TI  - Simultaneous quantification of volitinib and gefitinib in rat plasma by HPLC
      MS/MS for application to a pharmacokinetic study in rats.
AB  - A rapid, simple, and accurate procedure was developed and validated for the
      simultaneous quantification of two anticancer agents, volitinib and gefitinib in
      rat plasma by high-performance liquid chromatography with tandem mass
      spectrometry. The samples were separated by gradient elution from a cyano column
      within five minutes, using 0.1% formic acid in acetonitrile and 10 mM ammonium
      formate solution (pH 3.0) as mobile phase. When plasma samples were deproteinated
      by adding methanol, the analytes in the extract were detected in the positive
      ionization mode with the tracer ion mass of 346.1 -> 145.1 for volitinib and
      446.8 -> 128.1 for gefitinib. The assay was determined to be valid in the
      concentration ranges of 2 to 1000 ng/mL for volitinib, and of 1 to 500 ng/mL for
      gefitinib. Intra- and interday accuracies ranged from 88.0 to 104.7% for
      volitinib and from 90.3 to 101%, for gefitinib. The precision of the assay ranged
      from 2.1 to 9.71% for volitinib and 2.31 to 12.1% for gefitinib. This method was
      successfully applied to a pharmacokinetic study of volitinib and gefitinib after
      the administration of an intravenous or oral dose, indicating that the developed
      assay can be used to simultaneously determine the concentrations of volitinib and
      gefitinib in rat plasma.

PMID- 28749012
TI  - Disulfide Bond Mimetics: Strategies and Challenges.
AB  - The activity profile of many biologically relevant proteins and peptides often
      relies on a precise 3D structural organization. In this context, disulfide bonds
      are natural covalent constraints that play a key role in driving and stabilizing
      the folding pattern of these molecules. Despite its prominent significance as
      structural motif, the disulfide bond itself is inherently unstable under
      physiological conditions, posing a major limit to the use and development of
      disulfide-rich peptides and proteins as molecular tools and drug lead compounds.
      To tackle this restriction, disulfide engineering with stable functional
      analogues has arisen a considerable interest. Here, the most popular approaches
      to disulfide replacement are reviewed and discussed with particular emphasis on
      advantages and limitations under both functional and synthetic perspectives.

PMID- 28749014
TI  - Use of the Control of Allergic Rhinitis and Asthma Test and pulmonary function
      tests to assess asthma control in pregnancy.
AB  - INTRODUCTION: Asthma is one of the most prevalent chronic medical conditions to
      complicate pregnancy. Similarly, active management strategies that prioritise
      asthma control in this vulnerable population can have a far-reaching impact. AIM:
      To describe lung function parameters and results of the Control of Allergic
      Rhinitis and Asthma Test (CARAT) questionnaire in pregnant asthmatics and to
      analyse correlations between lung function tests and CARAT results. METHODS: All
      pregnant asthmatics who performed spirometry and CARAT between September 2014 and
      August 2015 were included. A medical records review was performed and data
      regarding demographics, sensitisation and medical prescriptions were recorded.
      Control of asthma and rhinitis was defined by CARAT total score (CARAT (T)) >=
      24; upper airways (U) control if CARAT (U) > 8; lower airways (L) control if
      CARAT (L) > 15. RESULTS: Forty-two pregnant asthmatics were included, with a
      median age (interquartile range)of 32 (27-34) years; all had a previous medical
      diagnosis of asthma and rhinitis, 76% were atopic, 94% sensitised to dust mites
      and 43% were polissensitised. More than 80% presented poor control (CARAT (T) <
      24) in the first assessment and 15% had a percentage forced expiratory volume in
      the first second < 80%. There were significant negative correlations between
      CARAT (L) and CARAT (T) scores and step-up of controller medication, (correlation
      coefficients  = -0.453 and -0.392, respectively). CONCLUSION: The use of tools
      such as spirometry and validated questionnaires to objectively assess asthma
      control during pregnancy should be routinely applied to assist in the management
      of these patients. These data reinforce the importance of close monitoring of
      pregnant asthmatics to achieve and maintain better disease control.

PMID- 28749013
TI  - Physiological vs. pharmacological signalling to myosin phosphorylation in airway
      smooth muscle.
AB  - KEY POINTS: Smooth muscle myosin regulatory light chain (RLC) is phosphorylated
      by Ca2+ /calmodulin-dependent myosin light chain kinase and dephosphorylated by
      myosin light chain phosphatase (MLCP). Tracheal smooth muscle contains
      significant amounts of myosin binding subunit 85 (MBS85), another myosin
      phosphatase targeting subunit (MYPT) family member, in addition to MLCP
      regulatory subunit MYPT1. Concentration/temporal responses to carbachol
      demonstrated similar sensitivities for bovine tracheal force development and
      phosphorylation of RLC, MYPT1, MBS85 and paxillin. Electrical field stimulation
      releases ACh from nerves to increase RLC phosphorylation but not MYPT1 or MBS85
      phosphorylation. Thus, nerve-mediated muscarinic responses in signalling modules
      acting on RLC phosphorylation are different from pharmacological responses with
      bath added agonist. The conditional knockout of MYPT1 or the knock-in mutation
      T853A in mice had no effect on muscarinic force responses in isolated tracheal
      tissues. MLCP activity may arise from functionally shared roles between MYPT1 and
      MBS85, resulting in minimal effects of MYPT1 knockout on contraction. ABSTRACT:
      Ca2+ /calmodulin activation of myosin light chain kinase (MLCK) initiates myosin
      regulatory light chain (RLC) phosphorylation for smooth muscle contraction with
      subsequent dephosphorylation for relaxation by myosin light chain phosphatase
      (MLCP) containing regulatory (MYPT1) and catalytic (PP1cdelta) subunits. RLC
      phosphorylation-dependent force development is regulated by distinct signalling
      modules involving protein phosphorylations. We investigated responses to
      cholinergic agonist treatment vs. neurostimulation by electric field stimulation
      (EFS) in bovine tracheal smooth muscle. Concentration/temporal responses to
      carbachol demonstrated tight coupling between force development and RLC
      phosphorylation but sensitivity differences in MLCK, MYPT1 T853, MYPT1 T696,
      myosin binding subunit 85 (MBS85), paxillin and CPI-17 (PKC-potentiated protein
      phosphatase 1 inhibitor protein of 17 kDa) phosphorylations. EFS increased force
      and phosphorylation of RLC, CPI-17 and MLCK. In the presence of the
      cholinesterase inhibitor neostigmine, EFS led to an additional increase in
      phosphorylation of MYPT1 T853, MYPT1 T696, MBS85 and paxillin. Thus, there were
      distinct pharmacological vs. physiological responses in signalling modules acting
      on RLC phosphorylation and force responses, probably related to degenerate G
      protein signalling networks. Studies with genetically modified mice were
      performed. Expression of another MYPT1 family member, MBS85, was enriched in
      mouse, as well as bovine tracheal smooth muscle. Carbachol concentration/temporal
      force responses were similar in trachea from MYPT1SM+/+ , MYPT1SM-/- and the
      knock-in mutant mice containing nonphosphorylatable MYPT1 T853A with no
      differences in RLC phosphorylation. Thus, MYPT1 T853 phosphorylation was not
      necessary for regulation of RLC phosphorylation in tonic airway smooth muscle.
      Furthermore, MLCP activity may arise from functionally shared roles between MYPT1
      and MBS85, resulting in minimal effects of MYPT1 knockout on contraction.

PMID- 28749015
TI  - Influence of application method on surface free-energy and bond strength of
      universal adhesive systems to enamel.
AB  - The aim of the present study was to determine the influence of different adhesive
      application methods and etching modes on enamel bond effectiveness of universal
      adhesives using shear bond strength (SBS) testing and surface free-energy (SFE)
      measurements. The adhesives Scotchbond Universal, All-Bond Universal, Adhese
      Universal, and G-Premio Bond were used. Prepared bovine enamel specimens were
      divided into four groups, based on type of adhesive, and subjected to the
      following surface treatments: (i) total-etch mode with active application; (ii)
      total-etch mode with inactive application; (iii) self-etch mode with active
      application; and (iv) self-etch mode with inactive application. Bonded specimens
      were subjected to SBS testing. The SFE of the enamel surfaces with adhesive was
      measured after rinsing with acetone and water. The SBS values in total-etch mode
      were significantly higher than those in self-etch mode. In total-etch mode,
      significantly lower SBS values were observed with active application compared
      with inactive application; in contrast, in self-etch mode there were no
      significant differences in SBS between active and inactive applications. A
      reduction in total SFE was observed for active application compared with inactive
      application. The interaction between etching mode and application method was
      statistically significant, and the application method significantly affected
      enamel bond strength in total-etch mode.

PMID- 28749016
TI  - Trends in study design and the statistical methods employed in a leading general
      medicine journal.
AB  - WHAT IS KNOWN AND OBJECTIVE: Study design and statistical methods have become
      core components of medical research, and the methodology has become more
      multifaceted and complicated over time. The study of the comprehensive details
      and current trends of study design and statistical methods is required to support
      the future implementation of well-planned clinical studies providing information
      about evidence-based medicine. Our purpose was to illustrate study design and
      statistical methods employed in recent medical literature. METHODS: This was an
      extension study of Sato et al. (N Engl J Med 2017; 376: 1086-1087), which
      reviewed 238 articles published in 2015 in the New England Journal of Medicine
      (NEJM) and briefly summarized the statistical methods employed in NEJM. Using the
      same database, we performed a new investigation of the detailed trends in study
      design and individual statistical methods that were not reported in the Sato
      study. RESULTS AND DISCUSSION: Due to the CONSORT statement, prespecification and
      justification of sample size are obligatory in planning intervention studies.
      Although standard survival methods (eg Kaplan-Meier estimator and Cox regression
      model) were most frequently applied, the Gray test and Fine-Gray proportional
      hazard model for considering competing risks were sometimes used for a more valid
      statistical inference. With respect to handling missing data, model-based
      methods, which are valid for missing-at-random data, were more frequently used
      than single imputation methods. These methods are not recommended as a primary
      analysis, but they have been applied in many clinical trials. Group sequential
      design with interim analyses was one of the standard designs, and novel design,
      such as adaptive dose selection and sample size re-estimation, was sometimes
      employed in NEJM. WHAT IS NEW AND CONCLUSION: Model-based approaches for handling
      missing data should replace single imputation methods for primary analysis in the
      light of the information found in some publications. Use of adaptive design with
      interim analyses is increasing after the presentation of the FDA guidance for
      adaptive design.

PMID- 28749017
TI  - Large institutional variations in use of androgen deprivation therapy with
      definitive radiotherapy in a population-based cohort of men with intermediate-
      and high-risk prostate cancer.
AB  - OBJECTIVE: To evaluate the pattern of use of androgen deprivation therapy (ADT)
      with definitive radiotherapy (RT) in men with prostate cancer (PCa) in a
      population-based study in Australia. PATIENTS AND METHODS: This is a prospective
      cohort of men with intermediate- and high-risk PCa, captured in the population
      based Prostate Cancer Outcome Registry Victoria, who were treated with definitive
      prostate RT between January 2010 and December 2015. The primary outcome of
      interest was ADT utilization. Chi-squared test for trend was used to evaluate the
      temporal trend in the use of ADT over the study period. Multivariate logistic
      regressions were used to evaluate the effects of patient-, tumour- and treatment
      related factors, and treatment institutions (public/ private and metropolitan/
      regional) on the likelihood of ADT utilization. RESULTS: A total of 1806 men were
      included in the study, 199 of whom (11%) had favourable National Comprehensive
      Cancer Network (NCCN) intermediate-risk disease (i.e. only one intermediate-risk
      feature, primary Gleason grade 3, and <50% biopsy core involved), 687 (38%) had
      unfavourable NCCN intermediate-risk disease, and 920 (51%) had high-risk disease.
      Of the 1806 men, 1155 (64%) received ADT with RT. Men with NCCN high-risk PCa
      (84%) were more likely to have ADT than men with favourable NCCN intermediate
      risk (32%) and unfavourable NCCN intermediate-risk (46%) PCa (P < 0.001). Men
      treated in public institutions (66%, vs 47% in private institutions; P < 0.001)
      and regional centres (78%, vs 59% in metropolitan institutions; P < 0.001) were
      more likely to receive ADT. There was a trend towards an increase in ADT
      utilization from 50% in 2010 to 64% in 2015 (P < 0.001). In multivariate analyses
      (adjusting for age, tumour-related factors, year of treatment and use of
      brachytherapy boost), treatment institution (public and regional) remained
      independently associated with increased likelihood of ADT utilization. Men with
      intermediate-risk PCa treated in regional and public institutions were 2.7 times
      (95% confidence interval [CI] 1.9-3.9; P < 0.001) and 2.8 times (95% CI 1.4-5.3;
      P = 0.002), more likely to receive ADT with RT, respectively, while men with high
      risk PCa treated in regional and public institutions were 3.1 times (95% CI 1.7
      5.7; P < 0.001) and 3.0 times (95% CI 1.7-5.4; P < 0.001), more likely to receive
      ADT with RT, respectively. CONCLUSION: This is the largest Australasian
      contemporary series reporting on the pattern of use of ADT with definitive
      prostate RT. While there was an increasing trend towards use of ADT over time,
      ADT still appeared to be underutilized in certain groups of patients who may
      benefit from ADT, with approximately one in five men with high-risk and one in
      two with unfavourable intermediate-risk PCa not receiving ADT with RT. There was
      notable variation in the use of ADT between public vs private and metropolitan vs
      regional institutions.

PMID- 28749018
TI  - Photoresponsive Conjugated Microporous Polymer Films Fabricated by
      Electrochemical Deposition for Controlled Release.
AB  - Stable controlled release system, conjugated microporous polymers (CMPs) with
      stimuli-responsive properties can be ideal structures because their 3D
      microporous matrix structure and possible stimulated response provide inherent
      switchable acceptor sites to capture and release guest molecules. Herein, the in
      situ electrochemical deposition of precursors (DTCzAzo) is utilized to construct
      highly crosslinked photoresponsive CMP films, which can reversibly undergo the
      trans-to-cis isomerization alternately with irradiation by 355 and 480 nm laser
      beams. The size of pores in CMP films changes tremendously during the process of
      trans-cis photoisomerization, to controllably capture, conserve, and release the
      guest molecules.

PMID- 28749019
TI  - The association of non-alcoholic fatty liver disease with lung function: A survey
      design analysis using propensity score.
AB  - BACKGROUND AND OBJECTIVE: Although both non-alcoholic fatty liver disease (NAFLD)
      and lung function are known to be associated with metabolic syndromes, few
      studies have evaluated the relationship between NAFLD and lung function. Our
      population-based study was conducted to investigate whether NAFLD, diagnosed by
      elevation of liver enzymes without other chronic liver disease or heavy alcohol
      drinking, is associated with lung function. METHODS: A survey design analysis was
      performed using national representative data of health and nutritional status of
      civilians in Korea (Korean National Health and Nutrition Examination Survey,
      KNHANES) between 2010 and 2012. The criteria for NAFLD diagnosis was elevated
      serum alanine aminotransferase (ALT) without other chronic liver disease or heavy
      alcohol drinking. Covariate-adjusted linear regression analyses and post
      stratification adjustments to the survey weights based on the propensity scores
      (PS) were conducted to evaluate the association of NAFLD and lung function,
      including the forced expiratory volume in 1 s (FEV1 ) and forced vital capacity
      (FVC). RESULTS: A total of 7417 subjects were included in this analysis. NAFLD
      was significantly associated with a lower FVC among males as determined by both
      the covariate-adjusted linear regression analysis (P < 0.01 in all multivariable
      models) and PS analysis (P = 0.007). In the PS analysis, NAFLD was significantly
      associated with lower FEV1 (P = 0.044) among males. Among females, NAFLD was
      associated with a lower FVC according to the linear regression analysis; this
      finding was not verified with the PS analysis. CONCLUSION: NAFLD was
      significantly associated with lower lung function and this relationship was more
      prominent among males.

PMID- 28749020
TI  - Artificial infection of sheep with multiple strains of Dichelobacter nodosus to
      induce footrot.
AB  - OBJECTIVES: To establish multiple strains of Dichelobacter nodosus in two flocks
      of sheep and to assess the virulence of five of these strains. METHODS: In
      experiment 1, sheep were challenged with five D. nodosus strains, which varied in
      both virulence and serotype. In experiment 2, consisting of four replicates
      (paddock groups), sheep were challenged with seven different strains of D.
      nodosus. In experiment 3, sheep were challenged with one of five D. nodosus
      strains. RESULTS: In experiment 1, at 28 days post challenge, four of the five
      challenge strains were present. Multiple-strain infections were present in 27
      feet, with isolates from three serogroups being recovered from 5 feet, and four
      serogroups from 1 foot. Challenged hind feet were more frequently affected (P <
      0.001). In experiment 2, four of the seven strains were recovered from one
      replicate and three strains from the remaining three replicates. Significantly
      more hind feet were affected (262/471, 55.6%) than front feet (198/481, 42%) (P <
      0.001). Clinically, in both experiments 1 and 2 the footrot resembled an
      intermediate form, despite the inclusion of a virulent strain of D. nodosus. In
      experiment 3, this virulent strain caused a higher prevalence of more severe
      footrot, a greater mean total foot score and, in Merino sheep, resulted in
      significantly lower weight gains (P < 0.05). Interaction between D. nodosus
      strain and breed occurred, with Polwarth sheep being significantly more severely
      affected by one strain than Merino sheep. DISCUSSION: The clinical expression of
      multiple-strain infections has implications for both research and control of
      footrot. A novel method of control is proposed.

PMID- 28749021
TI  - Prophylactic and therapeutic efficacy of Australian-registered insecticide
      formulations against Old World screwworm (Chrysomya bezziana) infestation.
AB  - OBJECTIVE: To determine the prophylactic and therapeutic efficacy of Australian
      registered insecticide formulations against Old World screwworm (OWS) myiases for
      potential use in screwworm containment and eradication programs. METHODS: The
      longevity of protection provided by six insecticidal formulations (subcutaneous
      ivermectin, doramectin and abamectin, a topically applied aqueous formulation of
      spinosad, ivermectin controlled-release capsule and a dicyclanil spray-on
      formulation) was tested using implants of 1st-instar OWS larvae on Javanese thin
      tail sheep. Therapeutic efficacy of four formulations (topical ivermectin,
      chlorfenvinphos/cypermethrin mixture, aerosol spinosad formulation and a
      formulation containing propetamphos and eucalyptus oil) was tested against 2- and
      4-day-old OWS strikes. RESULTS: Both the ivermectin capsule and dicyclanil spray
      on formulation gave 100% protection against screwworm implants for the full 12
      weeks of the study. Ivermectin, doramectin and abamectin administered SC all gave
      100% protection at 3 days post-treatment, but at 2 weeks the protection had
      become incomplete. Spinosad dipping did not give complete protection at any time.
      All four therapeutic treatments gave complete resolution of 2-day-old strikes and
      topical ivermectin, spinosad and chlorfenvinphos/cypermethrin, but not the
      propetamphos/eucalyptus oil formulation, gave complete resolution of all 4-day
      old strikes. CONCLUSION: Dicyclanil spray-on and ivermectin capsule formulations,
      both registered for use in sheep, but not for cattle or other livestock species,
      gave much longer protection against screwworm implants than the currently
      recommended SC ivermectin. Pre-emptive action to facilitate rapid deployment of
      these formulations in the event of a screwworm incursion is urgently needed.

PMID- 28749022
TI  - Effects of GnRH, a progesterone-releasing device, and energy balance on an
      oestrus synchronisation program in anoestrous dairy cows.
AB  - OBJECTIVE: The aim of this research was to study the roles of the day 0 energy
      balance and gonadotrophin-releasing hormone (GnRH) and progesterone levels on
      dominant follicle (DF) and corpus luteum (CL) development during the first 7 days
      of a gonadotrophin-prostaglandin-gonadotrophin (GPG) + progesterone (P4) program
      in anoestrous dairy cows. METHODS: Cows (n = 81) were allocated to one of the
      three treatments: (1) GPG + P4 (days 0 and 9, 100 ug GnRH; day 0-7, intravaginal
      P4 device; day 7, 500 ug PGF2alpha ); (2) GPG (as for treatment 1 but excluding
      the P4 device) and (3) prostaglandin + GnRH + P4 (as for treatment 1, but
      excluding day 0 GnRH). DF and CL size, plasma concentrations of insulin, insulin
      like growth factor-I (IGF-I) and non-esterified fatty acid (NEFA) were measured
      on days 0 and 7. RESULTS: The proportion of cows with a CL on day 7 was
      significantly different between groups (GPG: 78%, GPG+P4: 69%, PGF2alpha + GnRH +
      P4: 42%, P = 0.02). The CL volume on day 7 was significantly associated with
      treatment, treatment by time postpartum and plasma concentrations of insulin, IGF
      I and NEFA. CONCLUSION: In cows without a CL present on day 0 of an oestrus
      synchronisation program, removal of the day 0 GnRH treatment led to reduced CL
      development; however, no effect of adding progesterone was found. In contrast, in
      cows with a CL present on day 0 inclusion of a progesterone device led to a
      higher CL volume, but removal of the first GnRH injection had no effect. Response
      to the treatment was affected by plasma concentrations of insulin, IGF-I and
      NEFA.

PMID- 28749024
TI  - Chemical stability of morphine and methadone, and of methadone in combination
      with acepromazine, medetomidine or xylazine, during prolonged storage in
      syringes.
AB  - OBJECTIVE: To assess the chemical and physical stability of morphine and
      methadone stored in syringes for 12 months and of methadone when mixed with
      acepromazine, medetomidine or xylazine. METHODS: A high-performance liquid
      chromatography (HPLC) technique was developed and validated for the analysis of
      morphine and methadone. Morphine and methadone were dispensed into syringes and
      stored at 25 degrees C/60% relative humidity (RH) and 40 degrees C/75% RH.
      Solutions containing mixtures of methadone combined with acepromazine,
      medetomidine or xylazine were stored in syringes at 25 degrees C/60%RH. At
      initiation, after 1 week and then 1, 3, 6, 9 and 12 months, samples were analysed
      by HPLC for the quantification of the morphine or methadone. Measured
      concentrations were assessed as a function of storage time and temperature using
      linear regression statistics to calculate stability. RESULTS: When stored at 40
      degrees C/75%RH as pre-dispensed syringes, severe physical and chemical changes
      were observed after the third month for both morphine and methadone. In contrast,
      at 25 degrees C/60%RH both drugs remained chemically stable for 12 months, with
      concentration variations not exceeding a 5% change from initiation as stipulated
      in VICH stability guidelines. When in combination with acepromazine or xylazine,
      methadone also remained chemically stable, but the combination with medetomidine
      failed stability criteria prior to 6 months. Precipitation compromised the
      physical stability of methadone in all unsealed syringes prior to 9 months'
      storage. CONCLUSION: Pre-dispensing morphine or methadone into unsealed syringes
      compromises the drugs' physical stability. Mixing of methadone with other drugs
      can degrade its chemical stability.

PMID- 28749026
TI  - Maxillary unicystic ameloblastoma in a 6-week-old filly evaluated with computed
      tomography.
AB  - CASE REPORT: A 6-week-old Thoroughbred filly was presented for evaluation of an
      expansile mass overlying the right nasal passage and causing respiratory stertor.
      On skull radiographs, there was a loculated, soft tissue-opaque mass identified
      dorsal to the right upper premolars and effacing the right nasal cavity. Computed
      tomography (CT) revealed a locally extensive mass with relatively benign
      characteristics located centrally on the tooth root apices of the deciduous
      second premolar (506). The mass extended axially into the right nasal cavity,
      occluding the meatuses and causing displacement of the nasal septum to the left.
      CLINICAL OUTCOME & SIGNIFICANCE: Surgical excision was not deemed feasible with
      an athletic future in mind and the owners elected to euthanase the filly.
      Histopathologically, the mass was consistent with unicystic ameloblastoma and was
      lined intermittently with palisading, columnar basal cells (ameloblast-like
      cells) overlying a zone containing stellate cells in loose stroma. To the
      authors' knowledge this is the first report of a CT scan of an equine
      ameloblastoma. Although histopathology was essential for definitive diagnosis, CT
      clearly defined the origin of the mass and identified its locally extensive,
      cystic nature, which enabled informed decisions to be made.

PMID- 28749027
TI  - Erratum.

PMID- 28749028
TI  - Neuroendodermal cyst in the fourth ventricle of a dog.
AB  - CASE REPORT: We describe the MRI appearance and surgical outcome of a rare
      neuroendodermal cyst in the fourth ventricle of a German Shorthaired Pointer. The
      dog presented with uncoordinated gait and occasional falling that increased when
      she became excited. The MRI appearance is shown and the surgical treatment
      described. Recurrence occurred on two occasions and the dog was euthanased.
      CONCLUSION: Recurrence of these cysts is highly likely unless there is complete
      surgical resection.

PMID- 28749029
TI  - Ecotype Variation of Methyl Eugenol Content in Tea Tree (Melaleuca alternifolia
      and Melaleuca linariifolia).
AB  - Methyl eugenol is a natural phenylpropanoid compound found in a wide range of
      plants used for food, flavouring, cosmetics, and health-care. As a suspected
      rodent carcinogen, methyl eugenol may also be harmful to humans when present in
      significant concentrations. Consequently, its level has been restricted in some
      foodstuffs and cosmetics for some markets. In order to assess the potential to
      breed uniformly low methyl eugenol cultivars for an essential oil crop, tea tree,
      the source of 'Oil of Melaleuca, terpinene-4-ol type', we examine levels in
      individual trees (n = 30) from two geographic regions and six terpene chemotypes.
      Overall, methyl eugenol levels were low in this species (Mean [SD] 354 [239] ppm,
      n = 30), much lower than levels predicted to be of toxicological concern. Within
      each chemotype, there was a lack of evidence for correlations between terpenoid
      constituents and methyl eugenol levels. Further support for the independence of
      methyl eugenol and terpene biosynthesis was evident from similar mean levels in
      selected (Mean [SD] 586 [339] ppm, n = 12) and undomesticated Melaleuca
      alternifolia trees (Mean [SD] 480 [299] ppm, n = 5) with terpinen-4-ol type oils.
      By contrast, methyl eugenol level varied by geographic origin and chemotype.
      Trees from the upland region, where there is a prevalence of terpinolene type
      trees, had lower average methyl eugenol levels than trees from the coastal
      region, where there is a prevalence of terpinen-4-ol and 1,8-cineole type trees.

PMID- 28749030
TI  - Health and economic burden of diabetes in Bangladesh: Priorities for attention
      and control.

PMID- 28749031
TI  - Unravelling proximate cues of mass flowering in the tropical forests of South
      East Asia from gene expression analyses.
AB  - Elucidating the physiological mechanisms of the irregular yet concerted flowering
      rhythm of mass flowering tree species in the tropics requires long-term
      monitoring of flowering phenology, exogenous and endogenous environmental
      factors, as well as identifying interactions and dependencies among these
      factors. To investigate the proximate factors for floral initiation of mast
      seeding trees in the tropics, we monitored the expression dynamics of two key
      flowering genes, meteorological conditions and endogenous resources over two
      flowering events of Shorea curtisii and Shorea leprosula in the Malay Peninsula.
      Comparisons of expression dynamics of genes studied indicated functional
      conservation of FLOWERING LOCUS T (FT) and LEAFY (LFY) in Shorea. The genes were
      highly expressed at least 1 month before anthesis for both species. A
      mathematical model considering the synergistic effect of cool temperature and
      drought on activation of the flowering gene was successful in predicting the
      observed gene expression patterns. Requirement of both cool temperature and
      drought for floral transition suggested by the model implies that flowering
      phenologies of these species are sensitive to climate change. Our molecular
      phenology approach in the tropics sheds light on the conserved role of flowering
      genes in plants inhabiting different climate zones and can be widely applied to
      dissect the flowering processes in other plant species.

PMID- 28749032
TI  - Hip internal rotation in cerebral palsy: does femoral derotation osteotomy
      influence abductor insufficiency?

PMID- 28749033
TI  - Co-occurring Down syndrome and SUCLA2-related mitochondrial depletion syndrome.
AB  - Mitochondrial DNA depletion syndrome 5 (MIM 612073) is a rare autosomal recessive
      disorder caused by homozygous or compound heterozygous pathogenic variants in the
      beta subunit of the succinate-CoA ligase gene located within the 13q14 band. We
      describe two siblings of Hispanic descent with SUCLA2-related mitochondrial
      depletion syndrome (encephalomyopathic form with methylmalonic aciduria); the
      older sibling is additionally affected with trisomy 21. SUCLA2 sequencing
      identified homozygous p.Arg284Cys pathogenic variants in both patients. This
      mutation has previously been identified in four individuals of Italian and
      Caucasian descent. The older sibling with concomitant disease has a more severe
      phenotype than what is typically described in patients with either SUCLA2-related
      mitochondrial depletion syndrome or Down syndrome alone. The younger sibling, who
      has a normal female chromosome complement, is significantly less affected
      compared to her brother. While the clinical and molecular findings have been
      reported in about 50 patients affected with a deficiency of succinate-CoA ligase
      caused by pathogenic variants in SUCLA2, this report describes the first known
      individual affected with both a mitochondrial depletion syndrome and trisomy 21.

PMID- 28749034
TI  - The One-Pot Directed Assembly of Cylinder-Forming Block Copolymer on Adjacent
      Chemical Patterns for Bimodal Patterning.
AB  - The direct self-assembly of cylinder-forming poly(styrene-block-methyl
      methacrylate) (PS-b-PMMA) block copolymer is successfully assembled into two
      orientations, according to the underlying guiding pattern in different areas.
      Lying-down and perpendicular cylinders are formed, respectively, depending on the
      design of chemical pattern: sparse line/space pattern or hexagonal dot array. The
      first chemical pattern composed of prepatterned cross-linked polystyrene (XPS)
      line/space structure has a period (LS ) equal to twice the intercylinder period
      of the block copolymer (L0 ). The PS-b-PMMA thin film on the prepared chemical
      template after thermal annealing forms a lying-down cylinder morphology when the
      width of the PS strips is less than the width of PS block in the PS-b-PMMA block
      copolymer. The morphology is only applicable at the discrete thickness of the PS
      b-PMMA film. In addition to forming the lying-down cylinders directly on the XPS
      guiding pattern, the cylinder-forming block copolymer can also be assembled in a
      perpendicular way on the second guiding pattern (the hexagonal dot array). The
      block copolymer films are registered into two orientations in a single directed
      self-assembly process. The features of the assembled patterns are successfully
      transferred down to the silicon oxide substrate.

PMID- 28749035
TI  - Comparison between target magnetic resonance imaging (MRI) in-gantry and
      cognitively directed transperineal or transrectal-guided prostate biopsies for
      Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 MRI lesions.
AB  - OBJECTIVE: To compare the detection rates of prostate cancer (PCa) in men with
      Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 abnormalities on 3-Tesla
      multiparametric (mp) magnetic resonance imaging (MRI) using in-bore MRI-guided
      biopsy compared with cognitively directed transperineal (cTP) biopsy and
      transrectal ultrasonography (cTRUS) biopsy. METHODS: This was a retrospective
      single-centre study of consecutive men attending the private practice clinic of
      an experienced urologist performing MRI-guided biopsy and an experienced
      urologist performing cTP and cTRUS biopsy techniques for PI-RADS 3-5 lesions
      identified on 3-Tesla mpMRI. RESULTS: There were 595 target mpMRI lesions from
      482 men with PI-RADS 3-5 regions of interest during 483 episodes of biopsy. The
      abnormal mpMRI target lesion was biopsied using the MRI-guided method for 298
      biopsies, the cTP method for 248 biopsies and the cTRUS method for 49 biopsies.
      There were no significant differences in PCa detection among the three biopsy
      methods in PI-RADS 3 (48.9%, 40.0% and 44.4%, respectively), PI-RADS 4 (73.2%,
      81.0% and 85.0%, respectively) or PI-RADS 5 (95.2, 92.0% and 95.0%, respectively)
      lesions, and there was no significant difference in detection of significant PCa
      among the biopsy methods in PI-RADS 3 (42.2%, 30.0% and 33.3%, respectively), PI
      RADS 4 (66.8%, 66.0% and 80.0%, respectively) or PI-RADS 5 (90.5%, 89.8% and
      90.0%, respectively) lesions. There were also no differences in PCa or
      significant PCa detection based on lesion location or size among the methods.
      CONCLUSION: We found no significant difference in the ability to detect PCa or
      significant PCa using targeted MRI-guided, cTP or cTRUS biopsy methods.
      Identification of an abnormal area on mpMRI appears to be more important in
      increasing the detection of PCa than the technique used to biopsy an MRI
      abnormality.

PMID- 28749036
TI  - Advantages of RNA-seq compared to RNA microarrays for transcriptome profiling of
      anterior cruciate ligament tears.
AB  - Microarrays and RNA-seq are at the forefront of high throughput transcriptome
      analyses. Since these methodologies are based on different principles, there are
      concerns about the concordance of data between the two techniques. The
      concordance of RNA-seq and microarrays for genome-wide analysis of differential
      gene expression has not been rigorously assessed in clinically derived ligament
      tissues. To demonstrate the concordance between RNA-seq and microarrays and to
      assess potential benefits of RNA-seq over microarrays, we assessed differences in
      transcript expression in anterior cruciate ligament (ACL) tissues based on time
      from-injury. ACL remnants were collected from patients with an ACL tear at the
      time of ACL reconstruction. RNA prepared from torn ACL remnants was subjected to
      Agilent microarrays (N = 24) and RNA-seq (N = 8). The correlation of biological
      replicates in RNA-seq and microarrays data was similar (0.98 vs. 0.97),
      demonstrating that each platform has high internal reproducibility. Correlations
      between the RNA-seq data and the individual microarrays were low, but
      correlations between the RNA-seq values and the geometric mean of the microarrays
      values were moderate. The cross-platform concordance for differentially expressed
      transcripts or enriched pathways was linearly correlated (r = 0.64). RNA-Seq was
      superior in detecting low abundance transcripts and differentiating biologically
      critical isoforms. Additional independent validation of transcript expression was
      undertaken using microfluidic PCR for selected genes. PCR data showed 100%
      concordance (in expression pattern) with RNA-seq and microarrays data. These
      findings demonstrate that RNA-seq has advantages over microarrays for
      transcriptome profiling of ligament tissues when available and affordable.
      Furthermore, these findings are likely transferable to other musculoskeletal
      tissues where tissue collection is challenging and cells are in low abundance.
      (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J
      Orthop Res 36:484-497, 2018.

PMID- 28749037
TI  - Transfusion for sickle cell disease in pregnancy: a single-centre survey.
AB  - INTRODUCTION: Sickle cell disease in pregnancy carries a high risk of maternal
      and fetal adverse outcomes. The use of prophylactic transfusions to reduce the
      risk of sickle complications is controversial. Current UK standards do not
      recommend the routine use of transfusion for sickle pregnancy. We examined
      transfusion episodes during sickle pregnancies in a single centre over an 11-year
      period. METHODS: We conducted a retrospective observational study of all
      pregnancies in patients with sickle cell disease who attended the joint
      obstetric/haematology clinic over an 11-year period. All pregnancies were managed
      according to a local protocol, which did not recommend routine transfusion.
      RESULTS: A total of 38 pregnancies (HbSS 22, HbSC 13, Hb S/beta thalassaemia 3)
      were included, with a mean age at booking of 29 years. A total of 61% of
      pregnancies required on-demand or emergency transfusion during the course of
      pregnancy or post-partum. Women requiring a transfusion during pregnancy had a
      higher mean number of hospital admissions in the previous year (1.11 vs 0.15, P =
      0.057), a significantly lower mean steady-state haemoglobin (85.0 vs 99.6 g L-1 ,
      P = 0.003) and a significantly lower mean haemoglobin at the pregnancy booking
      visit. (86.1 vs 99.5 g L-1 , P = 0.02). CONCLUSION: In sickle pregnancies
      assigned to standard management in a single centre, a high proportion of women
      required on-demand transfusion. Possible pre-pregnancy factors predictive of a
      need for transfusion include lower baseline haemoglobin and number of hospital
      admissions in the previous 12 months.

PMID- 28749038
TI  - Effect of fabrication strategy on the enantioseparation performance of beta
      cyclodextrin-functionalized polymethacrylate monoliths: A comparative evaluation.
AB  - To evaluate the effect of the preparation strategy on the enantioseparation
      performance of beta-cyclodextrin-functionalized monoliths, a series of beta
      cyclodextrin-functionalized organic polymeric monolithic columns were prepared
      through two-step, single-step, and one-pot approaches, using the same
      cyclodextrin, linker-spacer, and crosslinker. Physicochemical characterization of
      the columns was carried out by determining the morphology, beta-cyclodextrin
      density, permeability, and chromatographic efficiency. For each type of
      monolithic column, the enantioresolution of 22 chiral compounds, including
      mandelic acid derivatives, nonsteroidal anti-inflammatory drugs, N-derivatized
      amino acids, and herbicides, was comparatively studied under optimum
      chromatographic conditions. The beta-cyclodextrin-functionalized monolithic
      columns prepared through the one-pot approach exhibited higher enantioresolution
      for most chiral compounds, and they have the advantage of good controllability
      and simple preparation. On the other hand, the enantioresolution obtained on
      columns prepared through the single-step approach was quite unsatisfactory, and
      therefore the effect of using different linking spacers and crosslinkers was
      studied. A significant improvement of enantioresolution for 2-chloro-mandelic
      acid was obtained by using N,N-methylenebisacrylamide instead of ethylene
      dimethacrylate as the crosslinker in the single-step preparation.

PMID- 28749039
TI  - Ventral-onlay buccal mucosa graft substitution urethroplasty for urethral
      stricture in women.
AB  - OBJECTIVE: To present our outcomes of ventral-onlay buccal mucosa graft (BMG)
      substitution urethroplasty in treating female urethral stricture (FUS). PATIENTS
      AND METHODS: We conducted a review of a prospectively collected database of 22
      consecutive women (median [range] age 50 [34-72] years) with urethral stricture
      who underwent ventral onlay BMG substitution urethroplasty after June 2012 and
      who had a minimum follow-up of 6 months (median 21.5, range 6-51 months). Data
      were analysed for stricture recurrence, change in median maximum urinary flow
      rate (Qmax ) and median post-void residual urine volume (PVR). Statistical
      analysis was performed using the Wilcoxon signed rank test, Student's t-test and
      the Mann-Whitney U-test. RESULTS: Freedom from stricture recurrence was achieved
      in 21/22 (95.5%) women. The median (range) Qmax significantly improved,
      increasing from 7 (3.5-11) to 18 (5-37) mL/s (P <0.05). The median (range) PVR
      was significantly reduced from 100 (0-300) to 15 (0-150) mL (P < 0.05). Short-
      and longer-term complication rates were low. One woman developed mild de novo
      stress urinary incontinence, which settled with conservative management by 6
      months. CONCLUSIONS: Early and medium-term results indicate that ventral onlay
      BMG substitution urethroplasty is an excellent treatment for FUS that can avoid
      the need for the repeat procedures regularly required after traditional
      endoscopic management.

PMID- 28749040
TI  - Retraction: 'MicroRNA-4656 is a prognostic factor and tumor suppressor in human
      pancreatic cancer through a downstream target of TrkA' by Xianglong Tan, Jinyong
      Lv, Guodong Zhao, Zhiming Zhao, Chenggang Li, Yong Xu and Minggen Hu.

PMID- 28749041
TI  - Rare case of a massive staphylococcal prostatic abscess presenting as an ischio
      rectal abscess.

PMID- 28749042
TI  - The use of intravesicular alteplase for thrombolysis in a dog with urinary
      bladder thrombi.
AB  - OBJECTIVE: To describe the use of alteplase for intravesicular thrombolysis in a
      dog after development of urinary tract obstruction from a blood clot in the
      urinary bladder. CASE SUMMARY: A 5.8 kg, 6.5-year-old female neutered Bichon
      Frise was presented for signs of acute hematuria. A complete blood count (CBC)
      revealed marked thrombocytopenia and leukopenia, and nonregenerative anemia. Bone
      marrow aspirate cytology revealed mild hypercellularity, mild megakaryocytic
      hyperplasia, mildly left-shifted erythroid maturation, and moderately left
      shifted myeloid maturation, suggesting ongoing recovery from an acute bone marrow
      insult. Thrombocytopenia and hematuria resolved concurrently; however, stranguria
      and oliguria developed acutely. Ultrasonography identified two large presumed
      thrombi within the urinary bladder. A urinary catheter was placed and 4 doses of
      0.5 mg of alteplase diluted in 10 mL of 0.9% sodium chloride were instilled into
      the bladder with a 4-hour dwell time at 12-hour intervals. Prothombin and
      activated partial thromboplastin times were monitored during therapy and remained
      within normal limits. One thrombus was successfully dissolved after 48 hours of
      therapy and the remaining thrombus was reduced in size and was voided upon
      removal of the urinary catheter. NEW OR UNIQUE INFORMATION PROVIDED: This report
      describes the use of alteplase in a dog for thrombolysis of intravesicular
      thrombi. In patients that develop intravesicular thrombi, intravesical
      instillation of alteplase can be considered as a method for dissolution of these
      thrombi.

PMID- 28749043
TI  - Transcriptome profiling reveals the immune response of goose T cells under
      selenium stimuli.
AB  - The goose is an economically important poultry species and a principal natural
      host of avian viruses. This study aimed to determine the effects of selenium on
      the immune response of geese. Under selenium stimulation, gene expression
      profiling was investigated using transcriptome sequencing. The selenoproteins
      were promoted by selenium stimulation, while the heat shock proteins, interleukin
      and interferons were mainly down-regulated. After comparison, 2228 differentially
      expressed genes were primarily involved in immune and environmental response, and
      infectious disease and genetic information processing related pathways were
      identified. Specifically, the enzymes of the lysosomes which acted as a safeguard
      in preventing pathogens were mostly up-regulated and six randomly selected
      differentially expressed genes were validated by quantitative polymerase chain
      reaction. In addition, the most proportional increased transcription factor
      family basic helix-loop-helix (bHLH) located in the 5' flank of selenoprotein P
      like protein for selenium metabolism was identified by response to the selenium
      stimulation in this study. These analyses show that selenium can promote immune
      function by activating selenoproteins, transcript factors and lysosome pathway
      related genes, while weakening cytokine content genes in geese.

PMID- 28749044
TI  - Video-assisted thoracoscopic lobectomy after percutaneous coronary intervention
      in lung cancer patients with concomitant coronary heart disease.
AB  - BACKGROUND: In recent years, based on clinical observations, the number of lung
      cancer patients with concomitant coronary heart disease (CHD) has gradually
      increased. However, because of the requirement of long-term anticoagulant therapy
      after percutaneous coronary intervention (PCI), some of these patients lose the
      opportunity for surgical treatment, resulting in tumor progression. The objective
      of this study was to determine the appropriate timing of video-assisted thoracic
      surgery (VATS) lobectomy after PCI without increasing perioperative
      cardiovascular risk. METHODS: This study retrospectively analyzed clinical data
      of patients with a combination of NSCLC and CHD who underwent selective pulmonary
      lobectomy by VATS in the early postoperative PCI period between 2010 and 2015 at
      Beijing Chaoyang Hospital, China. RESULTS: Fourteen patients received VATS
      lobectomy after PCI. The disease had progressed to T stage in two patients after
      PCI. No perioperative death occurred. Two patients suffered postoperative atrial
      fibrillation: one had a pulmonary infection, and the other had acute coronary
      syndrome. All patients recovered and were discharged. CONCLUSION: For NSCLC
      patients with severe CHD, the use of VATS lobectomy in the early postoperative
      PCI period could not only advance the timing of surgery, but may also control
      perioperative hemorrhage and CHD event risks within acceptable ranges, which
      could provide more patients with an opportunity to undergo surgical treatment.

PMID- 28749045
TI  - Factors related to recurrence of idiopathic granulomatous mastitis: what do we
      learn from a multicentre study?
AB  - BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare chronic
      inflammatory disease of the breast with unknown aetiology. Its treatment is
      controversial and the recurrence rate is high. The objectives of this study were
      to examine the demographic, sociocultural and clinical characteristics observed
      among a large cohort of IGM patients from Turkey and to identify factors related
      to the recurrence of IGM. METHODS: The study was designed as a multicentre
      retrospective study including 22 breast centres in Turkey. A total of 720 IGM
      patients are included in the study. Patient data were obtained from the patient's
      files and electronic records based on the study protocol. Patients' demographic,
      clinical, radiological, treatment and recurrence of IGM related characteristics
      were recorded. RESULTS: Our results revealed a statistically significant
      association between IGM recurrence and history of pregnancy, breastfeeding,
      breast infection and smoking (P < 0.05). Having a chronic systematic disease,
      oral contraceptive, analgesic and herbal medicine consumptions, treatment choice,
      education, place of birth and current residence were not found to be associated
      with IGM recurrence (P > 0.05). CONCLUSION: Our findings show that history of
      pregnancy, breastfeeding, breast infection and smoking were the risk factors for
      IGM recurrence. As current treatment methods did not affect IGM recurrence,
      recurrence-related factors, such as breast infection and smoking, should be
      considered to eliminate while focusing on less invasive local treatment research.

PMID- 28749046
TI  - Pot Economy in the Total Synthesis of Estradiol Methyl Ether by Using an
      Organocatalyst.
AB  - Enantioselective total synthesis of estradiol methyl ether has been accomplished
      in a pot-economical manner using five reaction vessels and four purifications.
      The key reaction is a diphenylprolinol silyl ether mediated domino Michael/aldol
      reaction to afford bicyclo[4.3.0]nonane derivatives, containing the A, C, and D
      rings of steroids, as a single isomer with excellent enantioselectivity. Six
      reactions such as oxidation, hydrogenation, formation of acid chloride, Friedel
      Crafts reaction, deprotection, and reduction can be carried out in the last one
      pot sequence.

PMID- 28749048
TI  - Adult Bochdalek hernia in a pregnant woman.

PMID- 28749047
TI  - Electric fields accelerate cell polarization and bypass myosin action in motility
      initiation.
AB  - Stationary symmetrical fish keratocyte cells break symmetry and become motile
      spontaneously but slowly. We found that applying electric field (EF) accelerates
      the polarization by an order of magnitude. While spontaneously polarized cells
      move persistently for hours, the EF-induced polarity is lost in a majority of
      cells when the EF is switched off. However, if the EF is applied for a long time
      and then switched off, the majority of cell move stably. Myosin inhibition
      abolishes spontaneous polarization, but does not slow down EF-induced
      polarization, and after the EF is turned off, motility does not stop; however,
      the cell movements are erratic. Our results suggest that the EF rapidly polarizes
      the cells, but that resulting polarization becomes stable slowly, and that the EF
      bypasses the requirement for myosin action in motility initiation.

PMID- 28749050
TI  - "Please amputate my child's arms".
AB  - Jeremy sustained bilateral complete brachial plexus injuries in an auto collision
      on an icy road a month before his third birthday. The accident rendered both
      upper extremities completely flail and insensate: he has no motor or sensory
      function of his shoulders, elbows, wrists, or digits. Jeremy does, however, have
      normal function of the lower extremities. Physical therapists have worked with
      the child for over a year with no noted improvement in arm function. Jeremy falls
      frequently, causing injury to his face and head, and occasionally, his arms get
      twisted or caught in his crib and his fingers turn blue. Jeremy's mother, who
      carries the main responsibility for his daily care, believes that his insensate
      arms are too heavy and "get in his way," causing the falls. She and Jeremy's
      father present to the orthopedic clinic at the children's hospital with the
      request of having both arms amputated. The primary orthopedic surgeon and the
      orthopedic team disagree with the parents that bilateral upper-extremity
      amputation offers any medical benefit, but Jeremy's mother tells the surgeon
      that, if he will not perform the surgery, her family will find a doctor who will.
      The surgeon, who feels ethically distressed by the parental insistence on this
      amputation in such a young child, requests an ethics consultation.

PMID- 28749049
TI  - Mineral trioxide aggregate enhances the osteogenic capacity of periodontal
      ligament stem cells via NF-kappaB and MAPK signaling pathways.
AB  - Mineral trioxide aggregate (MTA), as a bioactive material, has a widespread
      application in clinical practice. To date, the effects of MTA on the
      proliferation and differentiation of human periodontal ligament stem cells
      (hPDLSCs) remain unclear. hPDLSCs were isolated from human periodontal ligament
      tissues and cultured with MTA conditioned media. Cell counting kit-8 (CCK-8)
      assay was performed to assess the proliferation capacity of MTA-treated hPDLSCs.
      Immunofluorescence assay, alkaline phosphatase (ALP) activity, alizarin red
      staining, real-time RT-PCR, and western blot analyses were used to investigate
      the odonto/osteogenic capacity of hPDLSCs as well as the involvement of NF-kappaB
      and MAPK pathways. ALP activity assay revealed that 2 mg/ml was the optimal
      concentration for the induction of hPDLSCs by MTA. The protein expression of DSP,
      RUNX2, OCN, OSX, OPN, DMP1, ALP, and COL-I in MTA-treated hPDLSCs was
      significantly higher than those in control group (p < 0.01). When hPDLSCs were
      treated with the inhibitors of NF-kappaB and MAPK pathways (U0126, SP600125,
      SB203580, and BMS345541), the effects of MTA on the differentiation of hPDLSCs
      were suppressed. Mechanistically, P65 was detected to transfer from cytoplasm to
      nuclei, as indicated by western blot and immunofluorescence assay. Moreover, MAPK
      related proteins and its downstream transcription factors were also upregulated
      in MTA-treated hPDLSCs. Together, mineral trioxide aggregate can promote the
      odonto/osteogenic capacity of hPDLSCs via activating the NF-kappaB and MAPK
      pathways.

PMID- 28749051
TI  - Genomic Justice and Imagined Communities.
AB  - In this issue of the Hastings Center Report, Maya Sabatello and Paul Appelbaum
      explore the assumptions about community embedded in the U.S. Precision Medicine
      Initiative, which aims to recruit donor-partners who reflect the United States'
      racial and ethnic diversity. As Sabatello and Appelbaum discuss, the initiative
      is like other national biobanking efforts in bringing to life an imagined genetic
      community in need of critical attention, and given the public-private forms of
      partnership at the heart of the PMI, such efforts could become avenues to deepen
      existing inequalities rather than to alleviate them. The notion of justice has
      underwritten debates about genomic medicine, informed consent, citizenship,
      benefit sharing, and profit making since the first national biobanking project
      emerged at the dawn of the twenty-first century. In a paradigmatic case, the
      creation, by an Icelandic company, of the deCODE genomic biobank opened up fierce
      debates about the proper relationship between public good and private gain and
      became the first global example of the economic and political implications that
      imagined genetic communities could have in our shared future. In Mexico, in 2001,
      the Icelandic case fueled a policy agenda to deal with global health justice and
      the prospects of a future market-based colonialism predicated on the intimate
      knowledge of DNA.

PMID- 28749052
TI  - Trump's Abortion-Promoting Aid Policy.
AB  - On the fourth day of his presidency, Donald Trump reinstated and greatly expanded
      the "Mexico City policy," which imposes antiabortion restrictions on U.S. foreign
      health aid. In general, the policy has prohibited U.S. funding of any family
      planning groups that use even non-U.S. funds to perform abortions; prohibited aid
      recipients from lobbying (again, even with non-U.S. money) for liberalization of
      abortion laws; prohibited nongovernment organizations from creating educational
      materials on abortion as a family-planning method; and prohibited health workers
      from referring patients for legal abortions in any cases other than rape, incest,
      or to save the life of the mother. The policy's prohibition on giving aid to any
      organization that performs abortions is aimed at limiting alleged indirect
      funding of abortions. The argument is that if U.S. money is used to fund
      nonabortion programs of an abortion-providing NGO, then the NGO can simply shift
      the money thus saved into its abortion budget. Outside the context of abortion,
      we do not reason this way. And the policy's remaining three prohibitions are
      deeply troubling.

PMID- 28749055
TI  - A Failure to Be Candid.
AB  - I was a second-year neonatal-perinatal fellow in a meeting between other members
      of the neonatal intensive care team and parents who had just received devastating
      news about their planned-for and highly desired baby, born after what had been an
      uncomplicated pregnancy. At home, a little sister was waiting to meet her new
      brother. These conversations are never easy, but this one I found particularly
      disturbing. John had been born at term via emergency cesarean section after his
      mother, Muriel, had come for a routine obstetrical visit and reported decreased
      fetal movement. The obstetrician had detected a very slow fetal heart rate and
      sent Muriel to the hospital for emergent delivery. John was born floppy, with no
      respiratory effort. He was resuscitated, but a heart rate was not detected until
      fifteen minutes after birth. Not until several months later did I discover what
      had troubled me so much in this family meeting.

PMID- 28749054
TI  - The Precision Medicine Nation.
AB  - The United States' ambitious Precision Medicine Initiative proposes to accelerate
      exponentially the adoption of precision medicine, an approach to health care that
      tailors disease diagnosis, treatment, and prevention to individual variability in
      genes, environment, and lifestyle. It aims to achieve this by creating a cohort
      of volunteers for precision medicine research, accelerating biomedical research
      innovation, and adopting policies geared toward patients' empowerment. As
      strategies to implement the PMI are formulated, critical consideration of the
      initiative's ethical and sociopolitical dimensions is needed. Drawing on
      scholarship of nationalism and democracy, we discuss the PMI's construction of
      what we term "genomic citizenship"; the possible normative obligations arising
      therefrom; and the ethical, legal, and social challenges that will ensue.
      Although the PMI is a work in progress, discussion of the existing and emerging
      issues can facilitate the development of policies, structures, and procedures
      that can maximize the initiative's ability to produce equitable and socially
      sensitive outcomes. Our analysis can also be applied to other population-based,
      precision medicine research programs.

PMID- 28749056
TI  - On Legalizing Physician-Assisted Death for Dementia.
AB  - Last November, soon after Colorado became the latest state to authorize physician
      assisted suicide, National Public Radio's The Diane Rehm Show devoted a segment
      to legalization of "physician assistance in dying," a label that refers to both
      physician-assisted suicide and voluntary active euthanasia. Although the segment
      initially focused on PAD in the context of terminal illness in general, it wasn't
      long before PAD's potential application to dementia patients came up. A caller
      said that her mother had Alzheimer's disease and was being cared for at great
      expense. Suspecting that she will suffer the same fate, the caller reported that
      she had included in her will "my specific request that if I should be diagnosed,
      and it is legal to do so, I would like to opt out of a life and many years of
      suffering." A few countries, such as the Netherlands and Belgium, already allow
      PAD for dementia in certain circumstances. It wouldn't be surprising to see a
      U.S. legalization effort in the coming years.

PMID- 28749057
TI  - How Long a Life Is Enough Life?
AB  - Humans have long been troubled by the prospect of old age and its culmination in
      death. Whether to rebel against or accept this fate have been wrestled with down
      through the centuries. But new medical technologies and the growing science of
      aging have sided with rebellion. We know that aging can be pushed back and
      improved in its quality. That progress is well under way, but now intensified by
      many scientists and Silicon Valley entrepreneurs. In 2016, Mark Zuckerberg and
      Priscilla Chan pledged three billion dollars toward eventually "preventing,
      curing or managing all diseases." And some visionaries have made the elimination
      of death or its indefinite postponement a goal. To put those aspirations in a
      broader context, it is helpful to keep in mind where population growth and aging
      trends stand. Apart from any success in the explicit efforts to increase
      longevity, there will be a steady increase in the number of elderly worldwide-and
      a much higher percentage of the elderly as part of the overall population. Most
      of the largest changes will be in developing countries. They will be overburdened
      by the death of the elderly from expensive chronic diseases-already a vexing
      problem for affluent countries.

PMID- 28749058
TI  - Conservationism and Bioethic.
AB  - The lead article in this issue of the Hastings Center Report (July-August 2017)
      explores the ideas underpinning the Precision Medicine Initiative, the effort
      announced by President Obama in 2015 to promote the development of treatments
      adjusted to genetic and other variations. Authors Maya Sabatello and Paul
      Appelbaum hold that the effort works by appealing to a sense of collective
      identity and shared commitment-an understanding that they call the "PMI nation."
      But what are the moral implications of this idea? Sabatello and Appelbaum's
      question about the impact of an imagined community is an unusual way of exploring
      a set of values questions. In the second article, Johann Brannmark defends what
      is, at least in bioethics, an unusual philosophical framework for moral values.
      Brannmark starts by calling attention to large, never-quite-solved problems with
      the field's going way of understanding personhood and autonomy, and then argues
      that the body of tradition, law, and international governance known as the human
      rights framework offers a solution to those problems. And a supplement to this
      issue offers a set of essays on a topic outside the usual range for bioethics:
      the prospect of "de-extinction"-that is, of using genetic and reproductive
      technologies to construct simulacra of extinct animals that might eventually be
      introduced into the wild.

PMID- 28749059
TI  - Expanding the Horizon of Our Obligations in the Clinician-Patient Relationship.
AB  - Johan Brannmark's article "Patients as Rights Holders," in this issue of the
      Hastings Center Report, squarely identifies some important problems with the way
      we in clinical practice conceive of our obligations to our patients. As a
      solution, he helpfully suggests augmenting our focus on autonomy and informed
      consent with a broader menu of considerations drawn from the literature on human
      rights. Respect for autonomy is, of course, one of the hallowed principles of
      bioethics. In our traditional understanding, our patients deserve our respect
      because they are capable of autonomous choice, and the way we demonstrate our
      respect is by seeking their informed consent for our care. This model is so
      deeply ingrained that many of us have difficulty imagining that there could be
      any other way of thinking about it. But this model has two very serious
      drawbacks, problems that speak to much of what is wrong with health care today.

PMID- 28749060
TI  - Artificial Wombs and Abortion Rights.
AB  - In a study published in late April in Nature Communications, the authors were
      able to sustain 105- to 115-day-old premature lamb fetuses-whose level of
      development was comparable to that of a twenty-three-week-old human fetus-for
      four weeks in an artificial womb, enabling the lambs to develop in a way that
      paralleled age-matched controls. The oldest lamb of the set, more than a year old
      at the time the paper came out, appeared completely normal. This kind of research
      brings us one step closer to providing excellent quality of life for premature
      newborns, but it also portends major legal and ethical questions, especially for
      abortion rights in America.

PMID- 28749061
TI  - Decision-Making for an Incapacitated Pregnant Patient.
AB  - Decisions about continuing or terminating a pregnancy touch on profound,
      individualized questions about bodily integrity, reproductive autonomy, deeply
      held values regarding one's capacity for parenthood, and, in the case of a high
      risk pregnancy, the risks one is willing to take to have a baby. So far as
      possible, reproductive decisions are made between a patient, in some cases her
      partner, and her medical provider. However, this standard framework cannot be
      applied if the patient lacks decision-making capacity. In this essay, we discuss
      one such case that came before our clinical ethics team. We describe the
      challenges of respecting a patient's reproductive preferences when the patient
      cannot share what those preferences are, and we argue that decisions regarding
      reproductive health care should not be treated with exceptionalism. Rather, they
      should proceed under the normal processes of surrogate decision-making, including
      the application of substituted judgment. This approach enables us to take the
      patient's values into account when considering the questions implicated in
      reproductive health care, just as we do for other kinds of health care decisions
      in which a patient's deeply held values are salient.

PMID- 28749062
TI  - The art of the cover.
AB  - Often, it's difficult to match up our cover artwork with the subjects of our lead
      articles and special reports. Of necessity, we sometimes turn to pure
      abstraction. How else to illustrate technical policy articles on subjects such as
      changing research protocols or informed consent, or abstract ideas like
      congruence, duality, imbalance, causality? At such times, we have to be pretty
      creative, and my search for cover art can be long and challenging. In the end, we
      hope that the reader will make the connection between cover and content. However,
      at other times, the subject of a lead article or special report overflows with
      artistic possibilities.

PMID- 28749063
TI  - Patients as Rights Holders.
AB  - Autonomy and consent have been central values in Western moral and political
      thought for centuries. One way of understanding the bioethical models that
      started to develop, especially in the 1970s, is that they were about the fusion
      of a long-standing professional ethics with the core values underpinning modern
      political institutions. That there was a need for this kind of fusion is
      difficult to dispute, especially since the provision of health care has in most
      developed countries become an ever more important concern of our political
      institutions, with governments playing a significant role in regulating and
      facilitating the provision of health care and in many countries even largely
      organizing it. There is, nevertheless, still room for dispute about how best to
      achieve this fusion and how to best think about autonomy and consent in a
      biomedical context. The simplest model we can have is probably about how being a
      person is largely about having the capacity of autonomous choice and that the
      main mode through which we exercise autonomy is by providing informed consent.
      Yet, liberal democracy's core idea that human beings have a high and equal value
      is also found in other accounts of the person. The human-rights framework
      provides an alternative model for thinking about personhood and about patient
      care. The human-rights approach is grounded, not in an account of autonomy
      (although it has something to say about autonomy), but in an account of the moral
      and political personhood that people possess merely by being human beings. In
      this approach, values like dignity and integrity, both highly relevant in a
      bioethical context, are identified as distinct values rather than being derived
      from and therefore reduced to respect for autonomous choice. The human-rights
      approach can supplement the problematic notion of autonomy that has been central
      to bioethics by placing this notion in a broader, strongly pluralistic framework.

PMID- 28749064
TI  - The Stepwise Reaction of Rhodium and Iridium Complexes of Formula [MCl2 (kappa4
      C,N,N',P-L)] with Silver Cations: A Case of trans-Influence and Chiral Self
      Recognition.
AB  - Acetonitrile suspensions of the dichlorido complexes [MCl2 (kappa4 C,N,N',P-L)]
      [M=Rh (1), Ir (2)] react with AgSbF6 in a 1:2 molar ratio affording the bis
      acetonitrile complexes [M(kappa4 C,N,N',P-L)(NCMe)2 ][SbF6 ]2 (3 and 4). The
      reaction takes place in a sequential manner and the intermediates can be isolated
      varying the M:Ag molar ratio. In a 2:1 molar ratio, it affords the dimetallic
      monochlorido-bridged compounds [{MCl(kappa4 C,N,N',P-L)}2 (MU-Cl)][SbF6 ] (5 and
      6). In a 1:1 molar ratio, the monosubstituted solvato-complexes [MCl(kappa4
      C,N,N',P-L)(Solv)][SbF6 ] (Solv=H2 O, MeCN, 7-10) were obtained. Finally, in a
      2:3 molar ratio, it gives complexes 11 and 12 of formula [{M(kappa4 C,N,N',P
      L)(NCMe)(MU-Cl)}2 Ag][SbF6 ]3 in which a silver cation joints two cationic
      monosubstituted acetonitrile-complexes [MCl(kappa4 C,N,N',P-L)(NCMe)]+ through
      the remaining chlorido ligands and two Ag???C interactions with one of the phenyl
      rings of each PPh2 group. In all the complexes, the aminic nitrogen and the
      central metal atom are stereogenic centers. In the trimetallic complexes 11 and
      12, the silver atom is also a stereogenic center. The formation of the cation of
      the dimetallic complexes 5 and 6, as well as that of the trimetallic complexes 11
      and 12, takes place with chiral molecular self-recognition. Experimental data and
      DFT calculations provide plausible explanations for the observed molecular
      recognition. The new complexes have been characterized by analytical,
      spectroscopic means and by X-ray diffraction methods.

PMID- 28749065
TI  - Concise Review: The High Cost of High Tech Medicine: Planning Ahead for Market
      Access.
AB  - Cellular therapies and other regenerative medicines are emerging as potentially
      transformative additions to modern medicine, but likely at a staggering financial
      cost. Public health care systems' budgets are already strained by growing and
      aging populations, and many private insurer's budgets are equally stretched. The
      current systems that most payers employ to manage their cash flow are not
      structured to absorb a sudden onslaught of very expensive prescriptions for a
      large portion of their covered population. Despite this, developers of new
      regenerative medicines tend to focus on the demands of regulators, not payers, in
      order to be compliant throughout the clinical trials phases, and to develop a
      product that ultimately will be approvable. It is not advisable to assume that an
      approved product will automatically become a reimbursed product, as examples from
      current practice in hematopoietic stem cell transplantation in the U.S.
      demonstrate; similarly, in Europe numerous Advanced-therapy Medicinal Products
      achieved market authorization but failed to secure reimbursement (e.g., Glybera,
      Provenge, ChondroCelect, MACI). There are however strategies and approaches that
      developers can employ throughout clinical development, in order to generate
      clinical and health economic data which will be necessary to demonstrate the
      value proposition of the new product and help ensure market access for patients;
      furthermore, performance based managed entry agreements coupled with post-launch
      evidence generation can help overcome challenges around product uncertainty at
      launch and reduce market access delays. Stem Cells Translational Medicine
      2017;6:1723-1729.

PMID- 28749066
TI  - Donor-Dependent and Other Nondefined Factors have Greater Influence on the
      Hepatic Phenotype than the Starting Cell Type in Induced Pluripotent Stem Cell
      Derived Hepatocyte-Like Cells.

PMID- 28749067
TI  - Haemolysis in haemodialysis.
AB  - Haemolysis in haemodialysis, although rare in current times, is associated with
      significant mortality and morbidity. As such prompt recognition, treatment,
      analysis of root cause and correction of underlying causative factors is crucial.
      Dialysate, extracorporeal circuit and patient related factors all contribute to
      haemolysis risk. Haemolysis can manifest with non-specific signs and symptoms
      including but not restricted to hypertension, nausea, pain (abdominal, chest,
      back) and dyspnoea. It may present acutely during the dialysis session or may
      take a protracted course. Potential life threating consequences include;
      hyperkalaemia induced cardiac arrhythmias, profound anaemia and associated acute
      coronary events and respiratory distress, and severe necrotizing pancreatitis.
      Chronic haemolysis results in impaired endothelial function thus contributing to
      the long-term cardiovascular risk profile in haemodialysis patients. Stringent
      national and international standards, technological advancements in membrane and
      dialysis equipment design, dialyser purification methods and water treatment
      systems have greatly reduced the incidence of haemolysis. Despite these
      improvements recognition of haemolysis risk and ongoing clinical vigilance is
      important.

PMID- 28749068
TI  - 'Trifecta' outcomes of robot-assisted partial nephrectomy in solitary kidney: a
      Vattikuti Collective Quality Initiative (VCQI) database analysis.
AB  - OBJECTIVES: To analyse the outcomes of robot-assisted partial nephrectomy (RAPN)
      in patients with a solitary kidney in a large multi-institutional database.
      PATIENTS AND METHODS: In all, 2755 patients in the Vattikuti Collective Quality
      Initiative database underwent RAPN by 22 surgeons at 14 centres in nine
      countries. Of these patients, 74 underwent RAPN with a solitary kidney between
      2007 and 2016. We retrospectively analysed the functional and oncological
      outcomes of these 74 patients. A 'trifecta' of outcomes was assessed, with
      trifecta defined as a warm ischaemia time (WIT) of <20 min, negative surgical
      margins, and no complications intraoperatively or within 3 months of RAPN.
      RESULTS: All 74 patients underwent RAPN successfully with one conversion to
      radical nephrectomy. The median (interquartile range [IQR]) operative time was
      180 (142-230) min. Early unclamping was used in 11 (14.9%) patients and zero
      ischaemia was used in 12 (16.2%). Trifecta outcomes were achieved in 38 of 66
      patients (57.6%). The median (IQR) WIT was 15.5 (8.75-20.0) min for the entire
      cohort. The overall complication rate was 24.1% and the rate of Clavien-Dindo
      grade <=II complications was 16.3%. Positive surgical margins were present in
      four cases (5.4%). The median (IQR) follow-up was 10.5 (2.12-24.0) months. The
      median drop in estimated glomerular filtration rate at 3 months was 7.0
      mL/min/1.72 m2 (11.01%). CONCLUSION: Our findings suggest that RAPN is a safe and
      effective treatment option for select renal tumours in solitary kidneys in terms
      of a trifecta of negative surgical margins, WIT of <20 min, and low operative and
      perioperative morbidity.

PMID- 28749069
TI  - Fatal Fat Embolism After Penis Enlargement by Autologous Fat Transfer: A Case
      Report and Review of the Literature.
AB  - Fat embolism is an incidental finding in cases of long bone fractures or other
      trauma, but it is also associated with liposuction and autologous fat transfer, a
      procedure where fat from liposuction is injected back into the same patient's
      face, breast, buttocks or penis. We here present a case of sudden death by fat
      embolism in a healthy young male, caused by a simple penis enlargement procedure,
      in which fat was injected into the penis shaft. We suggest that the risk of fat
      embolization might be higher when pretraumatized tissue is subjected to fat
      injection, like in this case, where a penis elongation was performed before the
      fat injection.

PMID- 28749071
TI  - Hepatic subcapsular hematoma breaking into the abdominal cavity after
      extracorporeal shock wave lithotripsy for pancreatic stones.

PMID- 28749070
TI  - Diagnostic accuracy of a five-point Likert scoring system for magnetic resonance
      imaging (MRI) evaluated according to results of MRI/ultrasonography image-fusion
      targeted biopsy of the prostate.
AB  - OBJECTIVE: To evaluate the accuracy of a magnetic resonance imaging (MRI)-based
      Likert scoring system in the detection of clinically significant prostate cancer
      (CSPC), using MRI/ultrasonography (US) image-fusion targeted biopsy (FTB) as a
      reference standard. PATIENTS AND METHODS: We retrospectively reviewed 1218 MRI
      detected lesions in 629 patients who underwent subsequent MRI/US FTB between
      October 2012 and August 2015. 3-Tesla MRI was independently reported by one of
      eight radiologists with varying levels of experience and scored on a five-point
      Likert scale. All lesions with Likert scores 1-5 were prospectively defined as
      targets for MRI/US FTB. CSPC was defined as Gleason score >=7. RESULTS: The
      median patient age was 64 years, PSA level 6.97 ng/mL and estimated prostate
      volume 52.2 mL. Of 1218 lesions, 48% (n = 581) were rated as Likert 1-2, 35% (n =
      428) were Likert 3 and 17% (n = 209) were Likert 4-5. For Likert scores 1-5, the
      overall cancer detection rates were 12%, 13%, 22%, 50% and 59%, respectively, and
      the CSPC detection rates were 4%, 4%, 12%, 33% and 48%, respectively. Grading
      using the five-point scale showed strong positive correlation with overall cancer
      detection rate (r = 0.949, P = 0.05) and CSPC detection rate (r = 0.944, P =
      0.05). By comparison, in Likert 4-5 lesions, significant differences were noted
      in overall cancer detection rate (63% vs 35%; P = 0.001) and CSPC detection rate
      (47% vs 29%; P = 0.027) for the more experienced vs the less experienced
      radiologists. CONCLUSIONS: The detection rates of overall cancer and CSPC
      strongly correlated with the five-point grading of the Likert scale. Among
      radiologists with different levels of experience, there were significant
      differences in these cancer detection rates.

PMID- 28749072
TI  - A Highly Efficient Chemiluminescence Probe for the Detection of Singlet Oxygen in
      Living Cells.
AB  - Singlet oxygen is among the reactive oxygen species (ROS) with the shortest life
      times in aqueous media because of its extremely high reactivity. Therefore,
      designing sensors for detection of 1 O2 is perhaps one of the most challenging
      tasks in the field of molecular probes. Herein, we report a highly selective and
      sensitive chemiluminescence probe (SOCL-CPP) for the detection of 1 O2 in living
      cells. The probe reacts with 1 O2 to form a dioxetane that spontaneously
      decomposes under physiological conditions through a chemiexcitation pathway to
      emit green light with extraordinary intensity. SOCL-CPP demonstrated promising
      ability to detect and image intracellular 1 O2 produced by a photosensitizer in
      HeLa cells during photodynamic therapy (PDT) mode of action. Our findings make
      SOCL-CPP the most effective known chemiluminescence probe for the detection of 1
      O2 . We anticipate that our chemiluminescence probe for 1 O2 imaging would be
      useful in PDT-related applications and for monitoring 1 O2 endogenously generated
      by cells in response to different stimuli.

PMID- 28749074
TI  - Crediting curiosity and creativity in young scientists: Beyond the standard
      publication record ....

PMID- 28749073
TI  - Arranging eukaryotic nuclear DNA polymerases for replication: Specific
      interactions with accessory proteins arrange Pols alpha, delta, and epsilon in
      the replisome for leading-strand and lagging-strand DNA replication.
AB  - Biochemical and cryo-electron microscopy studies have just been published
      revealing interactions among proteins of the yeast replisome that are important
      for highly coordinated synthesis of the two DNA strands of the nuclear genome.
      These studies reveal key interactions important for arranging DNA polymerases
      alpha, delta, and epsilon for leading and lagging strand replication. The CMG
      (Mcm2-7, Cdc45, GINS) helicase is central to this interaction network. These are
      but the latest examples of elegant studies performed in the recent past that lead
      to a much better understanding of how the eukaryotic replication fork achieves
      efficient DNA replication that is accurate enough to prevent diseases yet allows
      evolution.

PMID- 28749075
TI  - Phototoxicity in live fluorescence microscopy, and how to avoid it.
AB  - Phototoxicity frequently occurs during live fluorescence microscopy, and its
      consequences are often underestimated. Damage to cellular macromolecules upon
      excitation light illumination can impair sample physiology, and even lead to
      sample death. In this review, we explain how phototoxicity influences live
      samples, and we highlight that, besides the obvious effects of phototoxicity,
      there are often subtler consequences of illumination that are imperceptible when
      only the morphology of samples is examined. Such less apparent manifestations of
      phototoxicity are equally problematic, and can change the conclusions drawn from
      an experiment. Thus, limiting phototoxicity is a prerequisite for obtaining
      reproducible quantitative data on biological processes. We present strategies to
      reduce phototoxicity, e.g. limiting the illumination to the focal plane and
      suggest controls for phototoxicity effects. Overall, we argue that phototoxicity
      needs increased attention from researchers when designing experiments, and when
      evaluating research findings.

PMID- 28749076
TI  - Serum and gene expression levels of CT-1, IL-6, and TNF-alpha after a lifestyle
      intervention in obese children.
AB  - BACKGROUND: Inflammation related molecules such as tumor necrosis factor-alpha
      (TNF-alpha), interleukin 6 (IL-6), and cardiotrophin-1 (CT-1) are highly
      expressed in obese individuals and could partly explain some comorbidities
      associated to obesity. In obese children, lifestyle interventions are able to
      lower inflammation and reduce cardiovascular risk factors associated with
      obesity. The aim of the present work was to study changes in inflammation-related
      molecules serum and peripheral blood mononuclear cells (PBMC) transcript levels
      after a 10-week lifestyle intervention in obese children and asses their
      potential association with glucose metabolism. METHODS: Twenty-three obese
      children (mean age 11.5 years; 48% males) underwent a 10-week lifestyle not
      controlled intervention trial. Anthropometric and biochemical measurements were
      analyzed. Transcript analysis for CT-1, IL-6, and TNF-alpha in PBMC were
      performed by RT-PCR. Serum cytokine levels were also measured at baseline and
      after 10-weeks. RESULTS: Participants achieved a significant reduction in body
      adiposity (0.34 decrease in body mass index-standard deviation), total
      cholesterol, and glucose levels after 10-weeks. A Significant decrease in serum
      TNF-alpha and C reactive protein (CRP) were observed. CT-1 transcript levels were
      significantly reduced (P = .005) after lifestyle intervention, and these changes
      were significantly correlated with changes in serum CT-1 levels (r = 0.451; P =
      .031). In multiple regression analysis baseline CT-1 transcript levels were
      positively associated with final insulin (R2 = 0.506; P = .035) and HOMA-IR
      values (R2 = 0.473; P = .034). CONCLUSIONS: We reported that serum CRP, TNF
      alpha, as well as PBMC CT-1 transcript levels were reduced after lifestyle
      intervention in obese children. More studies are needed to clarify the role of
      inflammation-related molecules in glucose metabolism.

PMID- 28749077
TI  - MiR-429 suppresses glioblastoma multiforme by targeting SOX2.
AB  - Accumulating evidence has shown that miR-429 plays an important role in the
      development and progression of tumour. However, the role of miR-429 in
      glioblastoma multiforme (GBM) remains largely unknown. The present study is
      designed to investigate the function of miR-429 in GBM and to explore the
      molecular mechanism underlying its function. The expression level of miR-429 was
      detected in GBM tissues and cell lines by quantitative real-time polymerase chain
      reaction. The effect of overexpression of miR-429 on in vitro cell proliferation,
      apoptosis and invasion was examined. Western blot analysis was used to detect the
      influence of miR-429 on the expression of target gene, and Pearson analysis was
      used to calculate the correlation between the expression of targets gene and the
      miR-429 in GBM tissues. Our study shows that miR-429 is downregulated in GBM
      tissues compared with noncancerous tissues (P < .01). In addition, the expression
      of miR-429 in GBM cell lines is also significantly lower (P < .01). Enforced
      expression of miR-429 inhibits GBM cells proliferation, induces apoptosis and
      suppresses invasion and leads to the downregulation of the SOX2 protein.
      Moreover, the expression level of miR-429 in GBM tissues shows inverse
      relationship with the expression level of SOX2 protein. Our findings suggest that
      miR-429 represents a potential tumour-suppressive miRNA and plays an important
      role in GBM progression by directly targeting SOX2.

PMID- 28749078
TI  - Vitamin D insufficiency correlates with peripheral B10 cells in patients with
      pituitary tumours.
AB  - The mechanism of pituitary gland tumour (PGT) is unclear. Aberrant immune
      tolerance is associated with the pathogenesis of tumour. Vitamin D and vitamin D
      receptor (VDR) are involved in the immune regulation. Interleukin (IL)-10 is one
      of the important immune regulatory molecules. This study aims to elucidate the
      role of VDR in the regulation of IL-10 in peripheral B cells of PGT patients. In
      this study, the peripheral blood samples were collected from PGT patients and
      healthy subjects. B cells were purified from the blood samples and analysed by RT
      qPCR and Western blotting. The correlation between the expression of IL-10 and
      VDR in the B cells was assessed. We observed that the serum VitD levels were
      negatively correlated with IL-10 expression in peripheral B cells of patients
      with PGT. Low levels of VDR expression were found in peripheral B cells of PGT
      patients. Exposure to VitD suppressed the expression of IL-10 in B cells. The VDR
      bounds the transcription factor of IL-10 to interfere with the expression of IL
      10 in B cells. The VDR agonists inhibited IL-10 expression in B cells from PGT
      patients. In conclusion, modulation of the expression of VDR can regulate the
      expression of IL-10 in peripheral B cells of PGT patients, which may contribute
      to the treatment of PGT.

PMID- 28749079
TI  - Recuperating lung decoction attenuates inflammation and oxidation in cigarette
      smoke-induced COPD in rats via activation of ERK and Nrf2 pathways.
AB  - Oxidative/antioxidative imbalance and chronic inflammation are the main
      contributors to the pathogenesis of chronic obstructive pulmonary disease (COPD).
      This study evaluated the effect of recuperating lung decoction (RLD) on
      inflammation and oxidative stress in rats with COPD induced by cigarette smoke
      and lipopolysaccharides (LPS). We used intravenous infusion of LPS combined with
      cigarette smoke exposure as a COPD rat model. We observed that RLD treatment
      increased the protein level of GSH and the ratio of GSH/GSSG but decreased 8-OHdG
      and 4-HNE in the serum. Furthermore, RLD significantly inhibited the expressions
      of IL-1beta, IL-6, TNF-alpha, and TGF-beta induced by cigarette smoke exposure,
      reduced the number of inflammatory cells in the bronchoalveolar lavage fluid, and
      alleviated the severity of cigarette smoke-induced emphysema. Mechanistically,
      RLD treatment prevented disease through downregulation of phosphorylated-ERK and
      Nrf2 expression, which regulates the production of proinflammatory cytokines. RLD
      treatment exerted a dramatic therapeutic effect on COPD. This study revealed a
      mechanism that RLD functions on the regulation of ERK signalling to inhibit
      inflammation.

PMID- 28749080
TI  - Cellular and genetic models of H6PDH and 11beta-HSD1 function in skeletal muscle.
AB  - Glucocorticoids are important for skeletal muscle energy metabolism, regulating
      glucose utilization, insulin sensitivity, and muscle mass. Nicotinamide adenine
      dinucleotide phosphate-dependent 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1)-mediated glucocorticoid activation in the sarcoplasmic reticulum
      (SR) is integral to mediating the detrimental effects of glucocorticoid excess in
      muscle. 11beta-Hydroxysteroid dehydrogenase type 1 activity requires glucose-6
      phosphate transporter (G6PT)-mediated G6P transport into the SR for its
      metabolism by hexose-6-phosphate dehydrogenase (H6PDH) for NADPH generation.
      Here, we examine the G6PT/H6PDH/11beta-HSD1 triad in differentiating myotubes and
      explore the consequences of muscle-specific knockout of 11beta-HSD1 and H6PDH.
      11beta-Hydroxysteroid dehydrogenase type 1 expression and activity increase with
      myotube differentiation and in response to glucocorticoids. Hexose-6-phosphate
      dehydrogenase shows some elevation in expression with differentiation and in
      response to glucocorticoid, while G6PT appears largely unresponsive to these
      particular conditions. When examining 11beta-HSD1 muscle-knockout mice, we were
      unable to detect significant decrements in activity, despite using a well
      validated muscle-specific Cre transgene and confirming high-level recombination
      of the floxed HSD11B1 allele. We propose that the level of recombination at the
      HSD11B1 locus may be insufficient to negate basal 11beta-HSD1 activity for a
      protein with a long half-life. Hexose-6-phosphate dehydrogenase was undetectable
      in H6PDH muscle-knockout mice, which display the myopathic phenotype seen in
      global KO mice, validating the importance of SR NADPH generation. We envisage
      these data and models finding utility when investigating the muscle-specific
      functions of the 11beta-HSD1/G6PT/H6PDH triad.

PMID- 28749081
TI  - Looking ahead through a fragile lens: Vulnerable narcissism and the future self.
AB  - Empirical data are lacking with regard to the degree to which self-absorbed
      hypersensitivity may be related to perceptions of the future self. The purpose of
      this study was to examine the relationship between vulnerable narcissism and
      several components of future orientation among psychiatric outpatients. A sample
      of 132 adult outpatients seeking mental health services completed measures
      assessing vulnerable narcissism, optimism, personal growth initiative and symptom
      distress, along with several questions regarding specific future outcomes.
      Correlation and regression analyses were used to examine relationships between
      vulnerable narcissism and future outlook domains, controlling for
      sociodemographic confounds and symptom distress. Significant negative
      associations were found between vulnerable narcissism and optimism, personal
      growth initiative, and expectations regarding mental health recovery and personal
      goal achievement. Clinical implications of these findings are discussed.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28749082
TI  - Impact of warm ischaemia time on postoperative renal function after partial
      nephrectomy for clinical T1 renal cell carcinoma: a propensity score-matched
      study.
AB  - OBJECTIVES: To analyse the effect of prolonged warm ischaemia time (WIT) on long
      term renal function after partial nephrectomy (PN), as controversy still exists
      as to whether prolonged WIT adversely affects the incidence of chronic kidney
      disease (CKD) after PN. PATIENTS AND METHODS: We reviewed data from 1816 patients
      who underwent PN for a clinical T1 renal tumour. The propensity scores for
      prolonged WIT were calculated with the shorter WIT group (<30 min) matched to the
      longer WIT group (>=30 min) in a 2:1 ratio. Multivariate analysis was used to
      determine independent predictors for occurrence of postoperative CKD [defined as
      an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 ] and major
      renal function deterioration (MRFD; defined as an eGFR decrease of >=25%
      postoperatively). RESULTS: After propensity score matching, there was no
      significant difference in CKD-free survival between the two WIT groups (P =
      0.787). Furthermore, longer WIT did not show any significant associations with
      postoperative CKD-free survival [hazard ratio (HR) 1.002, 95% confidence interval
      (CI) 0.989-1.015; P = 0.765) and MRFD-free survival (HR 1.014, 95% CI 1.000
      1.028; P = 0.055). From further subgroup analyses using more specific WIT
      thresholds (<=20, 21-30, 31-40, 41-50, >=50 min) and status of preoperative CKD,
      no significant differences were noted in CKD and MRFD-free survival amongst the
      subgroups (all P > 0.05). CONCLUSIONS: Prolonged WIT was not associated with
      increased incidence of CKD or MRFD after PN.

PMID- 28749084
TI  - Growth charts for cerebral palsy: still imperfect, but gaining in value.

PMID- 28749083
TI  - Evidence of bone marrow downregulation in brain-dead rats.
AB  - Experimental findings support the evidence of a persistent leucopenia triggered
      by brain death (BD). This study aimed to investigate leucocyte behaviour in bone
      marrow and blood after BD in rats. BD was induced using intracranial balloon
      catheter inflation. Sham-operated (SH) rats were trepanned only. Thereafter bone
      marrow cells were harvested every six hours from the femoral cavity and used for
      total and differential counts. They were analysed further by flow cytometry to
      characterize lymphocyte subsets, granulocyte adhesion molecules expression and
      apoptosis/necrosis [annexin V/propidium iodide (PI) protocol]. BD rats exhibited
      a reduction in bone marrow cells due to a reduction in lymphocytes (40%) and
      segmented cells (45%). Bone marrow lymphocyte subsets were similar in BD and SH
      rats (CD3, P = 0.1; CD4, P = 0.4; CD3/CD4, P = 0.4; CD5, P = 0.4, CD3/CD5, P =
      0.2; CD8, P = 0.8). Expression of L-selectin and beta2 -integrins on granulocytes
      did not differ (CD11a, P = 0.9; CD11b/c, P = 0.7; CD62L, P = 0.1). There were no
      differences in the percentage of apoptosis and necrosis (Annexin V, P = 0.73; PI,
      P = 0.21; Annexin V/PI, P = 0.29). In conclusion, data presented suggest that the
      downregulation of the bone marrow is triggered by brain death itself, and it is
      not related to changes in lymphocyte subsets, granulocyte adhesion molecules
      expression or apoptosis and necrosis.

PMID- 28749085
TI  - A pilot study evaluating the prognostic utility of platelet indices in dogs with
      septic peritonitis.
AB  - OBJECTIVE: To characterize platelet indices at time of diagnosis of septic
      peritonitis in dogs and to assess the relationship between platelet parameter
      data and survival to discharge in dogs treated surgically. DESIGN: Retrospective,
      observational, descriptive pilot study from 2009 to 2014. SETTING: University
      teaching hospital. ANIMALS: Forty-eight dogs diagnosed with septic peritonitis
      were included in this study. Thirty-six dogs had surgical source control. Blood
      samples from 46 healthy control dogs were used for reference interval (RI)
      generation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Dogs with septic
      peritonitis had significantly increased mean values for mean platelet volume
      (MPV), plateletcrit (PCT), and platelet distribution width (PDW) with increased
      proportions of dogs having values above the RI compared to healthy dogs. A
      significantly increased proportion of dogs with septic peritonitis had platelet
      counts above (12.5%) and below (8.3%) the RI, with no significant difference in
      mean platelet count compared to healthy dogs. No significant differences in the
      mean platelet count, MPV, PCT, or PDW were found between survivors and
      nonsurvivors in dogs with surgical source control; however, dogs with MPV values
      above the RI had significantly increased mortality compared to dogs within the RI
      (P = 0.025). Values outside the RI for other platelet parameters were not
      associated with significant differences in mortality. CONCLUSIONS: Dogs with
      septic peritonitis have increased frequency of thrombocytosis and
      thrombocytopenia with increased MPV, PCT, and PDW. An increased MPV may be a
      useful indicator of increased risk of mortality in dogs treated surgically.

PMID- 28749086
TI  - 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) reduces hepatic injury in
      concanavalin A-treated mice.
AB  - 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), a chemically synthesized
      monoacetyldiaglyceride, is one of the constituents in Sika deer antlers and has
      been known traditionally as having immunomodulatory effects. However, the
      mechanism by which PLAG controls neutrophil migration, which evokes liver injury
      in the hepatitis animal model, remains largely unknown. This study was designed
      to evaluate the immunomodulatory effects of PLAG on cytokine secretion and
      neutrophil migration in vivo and in vitro. Concanavalin A (Con A) induced
      leukocyte infiltration in the liver and increased plasma cytokine levels.
      Pretreatment with PLAG reduced the levels of interleukin (IL)-4, IL-6, IL-10, and
      CXCL2, but maintained interferon (IFN)-gamma levels and modulated neutrophil
      recruitment toward the liver. Furthermore, the mRNA and protein levels of IL-4
      and CXCL2 in liver tissue were also decreased in the Con A-treated mice. Liver
      histology analyses showed that PLAG reduced Con A-induced hepatic necrosis, which
      was accompanied by leukocyte infiltration. The in vitro studies revealed that
      PLAG reduced IL-4 secretion in Con A stimulated T cell and blocked signal
      transducer and activator of transcription 6 (STAT6) Con A induced hepatocyte.
      PLAG attenuated IL-4 induced activation of atypical protein kinase C (PKC)/STAT6
      in hepatocytes and inhibited neutrophil migration toward the liver tissue through
      suppression of IL-8/vascular cell adhesion molecule (VCAM) expression. These
      results suggest that PLAG could mitigate excess neutrophil migration into liver
      tissue and potentially have a therapeutic effect on immune-mediated liver injury.

PMID- 28749087
TI  - Coaction of individual and environmental factors: a review of intensive therapy
      paradigms for children with unilateral spastic cerebral palsy.
AB  - : Evidence-based treatment approaches for children with unilateral spastic
      cerebral palsy are expanding and being modified to fit the constraints of
      families and the child receiving treatment. In this review, we first provide an
      overview of a theoretical framework that considers the intricate interactions
      between the individual child and the environment in which treatment is provided.
      Next, we describe intensive interventions that have strong support for their
      efficacy. We also highlight the heterogeneity with which children respond to
      these approaches. Individual characteristics that might affect responsiveness are
      summarized. We propose that a one-size-fits-all approach may not be as
      efficacious as approaches based on the specific brain damage and resulting
      development of the corticospinal tract. Finally, we review evidence suggesting
      that the environment can be structured to promote opportunities for intensive
      practice and self-generated movement-two important aspects of efficacious
      treatments. Emphasis is placed on intensive home programs delivered by
      caregivers. WHAT THIS PAPER ADDS: Considerable variability exists in how children
      with unilateral spastic cerebral palsy respond to intensive upper extremity
      therapies. Individual and environmental factors interact to shape responsiveness.

PMID- 28749088
TI  - Anxiety in youth with asthma: A meta-analysis.
AB  - OBJECTIVES: Anxiety often presents comorbidly with asthma in youth under 18;
      however, prevalence rates are unclear. The aim of this review was to provide an
      up-to-date analysis of the literature investigating the prevalence of anxiety
      disorders, and comparisons of anxiety disorders and symptomatology in youth with
      asthma, compared to those without. METHODS: A systematic search was conducted
      using the databases PsycINFO, MEDLINE, EMBASE, and CINAHL. RESULTS: The search
      process produced 15 studies (n = 7443) reporting data on youth with asthma and
      anxiety disorders, 11 studies (n = 10 332) reporting data on youth with and
      without asthma and anxiety disorders, and 28 studies (n = 5848) reporting data on
      youth with and without asthma and anxiety symptomatology. Youth with asthma had
      an anxiety disorder prevalence rate of 22.7%. Youth with asthma also had a
      greater number of anxiety disorders, compared to those without asthma (d = 0.37,
      95%CI: 0.24-0.50, P < 0.001), and higher levels of anxiety symptomatology than
      youth without asthma (d = 0.29, 95%CI: 0.19-0.39, P < 0.001). CONCLUSIONS: Youth
      with asthma display a prevalence rate for anxiety disorders that is more than
      three times higher than the prevalence in healthy youth. For the specific anxiety
      disorders investigated, elevated prevalence rates for youth with asthma were also
      found. Future research needs to focus on the factors that mediate or predict the
      development and maintenance of anxiety in youth with asthma and the development
      of clinically efficacious treatments.

PMID- 28749089
TI  - Cognitive Deficits in Patients With Neuropsychiatric Symptoms: A Comparative
      Study Between Behavioral Variant Frontotemporal Dementia and Primary Psychiatric
      Disorders.
AB  - OBJECTIVE: To compare neuropsychological profiles in behavioral variant
      frontotemporal dementia (bvFTD) with its most common primary psychiatric
      differential diagnoses, major depressive disorder (MDD), bipolar disorder (BD),
      and schizophrenia, in older patients with active symptoms. METHODS: We included
      patients from different cohorts with MDD (DSM-IV-TR: 296.20-296.23, 296.30
      296.33; n = 42; mean +/- SD age, 72.0 +/- 8.0 years; female = 57.1%) included
      from 2002 to 2007, noneuthymic BD (DSM-IV-TR: 296.00-296.06, 296.40-296.46,
      296.50-296.56, 296.60-296.66, 296.7; DSM-IV-TR: 296.89; DSM-IV-TR: 296.80; n =
      41; age, 71.7 +/- 8.8 years; female = 53.7%) included from 2011 to 2015,
      nonremitted schizophrenia (DSM-IV-TR: 295.10, 295.20, 295.30, 295.60, 295.90; n =
      47; age, 67.5 +/- 7.1 years; female = 66%) included from 2006 to 2008, or
      probable/definite bvFTD (n = 173; age, 62.6 +/- 8.0 years; female = 39.9%)
      (Frontotemporal Dementia Consensus criteria) included from 2000 to 2015 and
      healthy controls (n = 78; age, 71.9 +/- 8.0 years; female = 71.8%) included from
      2005 to 2007. Neuropsychological tests concerned the domains of attention and
      working memory, verbal memory, verbal fluency, and executive functioning.
      Analyses of variance were performed with age, gender, and education level as
      covariates. Post hoc Bonferroni tests were used to detail group differences.
      RESULTS: Compared to the healthy controls, both the bvFTD and primary psychiatric
      disorder groups showed significant impairment on all cognitive domains. Executive
      function was more disturbed in all primary psychiatric disorders compared to
      bvFTD (P < .001). Attention and working memory were significantly better in the
      bvFTD and schizophrenia groups compared to the MDD and BD groups (P < .001). For
      verbal memory, the bvFTD group scored significantly higher compared to patients
      with schizophrenia, BD, or MDD (P < .001). Patients with bvFTD had significantly
      lower scores on verbal fluency, especially due to Animal Naming, in comparison
      with the BD group (P < .001); however, these scores were not significantly
      different from those of MDD or schizophrenia patients. CONCLUSIONS: Cognitive
      deficits in bvFTD are less severe than in primary psychiatric disorders with
      active symptoms. This indicates that in the differential diagnosis of bvFTD,
      disturbances on tests for cognitive performance do not rule out primary
      psychiatric diagnoses.

PMID- 28749091
TI  - Efficacy of Ziprasidone Augmentation of Escitalopram for Cognitive Symptoms of
      Major Depressive Disorder.
AB  - OBJECTIVE: To examine the efficacy of adjunctive ziprasidone for cognitive
      symptoms in adult patients with major depressive disorder (MDD) experiencing
      persistent symptoms after 8 weeks of open-label escitalopram. METHODS: This post
      hoc analysis was conducted on a database derived from a previously published
      study. The parent study was a multicenter, parallel, randomized, double-blind,
      placebo-controlled trial conducted at 3 academic medical centers in the United
      States from July 2008 to October 2013. The participant pool consisted of 139
      outpatients with persistent symptoms of MDD, according to DSM-IV criteria,
      following an 8-week open label, flexible-dose trial of escitalopram. Subjects
      were randomly assigned (1:1, N = 139) to adjunctive fixed-dose ziprasidone
      (escitalopram + ziprasidone, n = 71) or adjunctive placebo (escitalopram +
      placebo, n = 68) with 8 weekly follow-up assessments. Primary outcome was
      clinical response according to the 17-item Hamilton Depression Rating Scale,
      which was defined as a 50% or greater reduction in scale scores. The
      Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire
      (CPFQ) was used to measure cognitive and executive dysfunction at each study
      visit. All statistical testing was conducted at the nominal, 2-sided, 0.05 level
      of significance. RESULTS: Adjunctive ziprasidone therapy did not result in
      significantly greater improvement in CPFQ scores compared to adjunctive placebo
      (P > .05). Residual cognitive symptoms were reported in a substantial number of
      patients who were considered responders to either adjunctive ziprasidone or
      placebo. CONCLUSIONS: In the present study, ziprasidone used adjunctively with
      the selective serotonin reuptake inhibitor escitalopram did not demonstrate a
      greater efficacy for cognitive symptoms in patients with MDD compared with
      adjunctive placebo. Future, well-designed studies examining the role of atypical
      antipsychotics or other augmentation versus switch strategies for cognitive
      symptoms in MDD are warranted.

PMID- 28749090
TI  - Relationships of Cerebrospinal Fluid Monoamine Metabolite Levels With Clinical
      Variables in Major Depressive Disorder.
AB  - OBJECTIVE: Many studies have investigated cerebrospinal fluid (CSF) monoamine
      metabolite levels in depressive disorders. However, their clinical significance
      is still unclear. We tried to determine whether CSF monoamine metabolite levels
      could be a state-dependent marker for major depressive disorder (MDD) based on
      analyses stratified by clinical variables in a relatively large sample. METHODS:
      Subjects were 75 patients with MDD according to DSM-IV criteria and 87 healthy
      controls, matched for age, sex, and ethnicity (Japanese). They were recruited
      between May 2010 and November 2013. We measured homovanillic acid (HVA), 5
      hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol
      (MHPG) in CSF samples by high-performance liquid chromatography. We analyzed the
      relationships of the metabolite levels with age, sex, diagnosis, psychotropic
      medication use, and depression severity. RESULTS: There was a weak positive
      correlation between age and 5-HIAA levels in controls (rho = 0.26, P < .016) and
      a similar trend in patients, while sex was unrelated to any metabolite. All
      monoamine metabolites in moderately to severely depressed patients (17-item
      Hamilton Depression Rating Scale score > 12) were significantly lower than those
      in controls (P < .0005 for all 3 metabolites). We found that antidepressants
      decreased the levels of 5-HIAA (rho = -0.39, P < .001) and MHPG (rho = -0.49, P <
      .0001) and that antipsychotics increased levels of HVA (rho = 0.24, P < .05).
      There was a strong correlation between HVA and 5-HIAA levels (controls: rho =
      0.79, P = .000001; MDD: rho = 0.66, P = .000001). HVA levels (rho = -0.43, P <
      .001) and 5-HIAA levels (rho = -0.23, P < .05), but not MHPG levels (rho = -0.18,
      P > .1), were related to depression severity. CONCLUSIONS: CSF 5-HIAA and HVA
      levels could be state-dependent markers in MDD patients. Since 5-HIAA levels
      greatly decrease with the use of antidepressants, HVA levels might be more useful
      in the clinical setting.

PMID- 28749092
TI  - Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How
      Long, and at What Frequency?
AB  - BACKGROUND: Ketamine, administered in subanesthetic doses, is an effective off
      label treatment for severe and even treatment-refractory depression; however,
      despite dozens of studies across nearly 2 decades of research, there is no
      definitive guidance on matters related to core practice issues. METHODS: This
      article presents a qualitative review and summary about what is known about
      ketamine dosing, rate of administration, route of administration, duration of
      treatment, and frequency of sessions. RESULTS: Ketamine is most commonly
      administered in the dose of 0.5 mg/kg, but some patients may respond to doses as
      low as 0.1 mg/kg, and others may require up to 0.75 mg/kg. The ketamine dose is
      conventionally administered across 40 minutes; however, safety and efficacy have
      been demonstrated in sessions ranging between 2 and 100 minutes in duration.
      Bolus administration is safe and effective when the drug is administered
      intramuscularly or subcutaneously. Whereas the intravenous route is the most
      commonly employed, safety and efficacy have been described with other routes of
      administration, as well; these include oral, sublingual, transmucosal,
      intranasal, intramuscular, and subcutaneous routes. Patients may receive a single
      session of treatment or a course of treatment during the acute phase, and
      treatment may rarely be continued for weeks to years to extend and maintain
      treatment gains in refractory cases. When so extended, the ideal frequency is
      perhaps best individualized wherein ketamine is dosed a little before the effect
      of the previous session is expected to wear off. CONCLUSIONS: There is likely to
      be a complex interaction between ketamine dose, session duration, route of
      administration, frequency of administration, and related practice. Until
      definitive studies comparing different doses, rates of administration, routes of
      administration, and other considerations are conducted, firm recommendations are
      not possible. From the point of view of clinical practicability, subcutaneous,
      intranasal, and oral ketamine warrant further study. If domiciliary treatment is
      considered, the risk of abuse must be kept in mind.

PMID- 28749093
TI  - Comparing low volume saphenous-obturator block with placebo and femoral-obturator
      block for anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Anterior cruciate ligament reconstruction (ACL-RC) is often
      associated with moderate to severe postoperative pain even with a multimodal
      analgesic regimen. We aimed to compare the analgesic efficacy of low volume
      saphenous-obturator block with placebo and femoral-obturator block in patients
      undergoing ACL-RC. METHODS: In a randomized controlled trial eighty-two patients
      undergoing ACL-RC with hamstring autograft were allocated to either low volume
      saphenous-obturator block, placebo block or femoral-obturator block. Ropivacaine
      0.75% was used for active blocks and saline for placebo. Primary outcome was pain
      scores at rest quantified as area-under-the-curve 0-6 hr postoperatively.
      Secondary outcomes were postoperative opioid consumption and pain localization in
      the knee. RESULTS: No statistical difference existed between groups in area-under
      the-curve 6 hr pain-scores. However, pain-scores were significantly lower in the
      two ropivacaine groups compared to placebo at emergence t=0 (P<0.018), at t=5
      (P<0.042) and at t=6 hours (P<0.002) postoperatively. Furthermore, ropivacaine
      blocks exhibited significantly reduced total opioid consumption (15.81 and 18.44
      mg) postoperatively compared with placebo (26.38 mg) (P<0.018). Patients
      receiving ropivacaine blocks localized pain in the posterolateral knee, whereas
      placebo block patients reported anteromedial and central pain. Other secondary
      outcomes were similar between groups. CONCLUSIONS: Low volume saphenous-obturator
      block is significantly more effective than placebo in reducing both early and
      late pain-scores as well as postoperative opioid consumption in patients
      undergoing ACL-RC. No statistical difference existed when comparing low volume
      saphenous-obturator block to femoral-obturator block regarding early and late
      pain-scores and postoperative opioid consumption.

PMID- 28749094
TI  - Superiority of ultrasound-guided Shamrock lumbar plexus block.
AB  - Ultrasound-guided lumbar plexus block (LPB) performed with the Shamrock approach
      has received much interest since the technique was first described in 2013. The
      technique is believed to be faster and easier to perform and possibly safer in
      regards to potential complications compared with other LPBs. In order to outline
      some favorable characteristics of the Shamrock LPB, we performed an exhaustive
      search of the current literature; even though it is rather limited. We have
      related the evidence to our own clinical experience about the block execution. We
      present a narrative review of the alleged superiority of the ultrasound-guided
      Shamrock LPB. Our aim was to assess some of the characteristics that we believe
      differentiate the Shamrock technique from other ultrasound-guided LPB techniques.
      We present graphical directions about how to carry out the Shamrock block, and we
      present novel magnetic resonance images illustrating the injectate spread around
      the lumbar plexus within the intrapsoas compartment after Shamrock guided
      injection of contrast enhanced local anesthetic. The Shamrock approach is easier,
      faster and better to visualise the LPB compared to other LPB techniques. The
      needle trajectory and needle tip location just lateral to the lumbar plexus
      probably reduces the risk of adverse effects and complications. Ultrasound guided
      lumbar plexus blockade is an expert technique. The Shamrock technique improves
      but does not eliminate all the challenges of ultrasound-guided LPB technique.

PMID- 28749095
TI  - A new arterial mechanical property indicator reflecting differences in invasive
      stimulus intensity induced by alteration of remifentanil concentration during
      laryngoscopy.
AB  - BACKGROUND: Reliable analgesia monitoring is not available for general
      anaesthesia cases. In 2003, we introduced a method to characterise arterial
      mechanical properties, which we termed arterial stiffness (K). However, it is
      unclear whether differences in K actually indicate changes in the intensity of a
      noxious stimulus. Thus, we examined the relationship between stress intensity and
      the value of K. METHODS: Thirty patients under general anesthesia were randomly
      divided into two remifentanil concentration groups (2 and 6 ng/mL). After a
      steady concentration of remifentanil was achieved for at least 3 minutes,
      laryngoscopy was performed. After completion of laryngoscopy, once the K value
      returned to near-baseline, laryngoscopy with endotracheal intubation was
      performed, and the value of K after the procedure was recorded and analyzed.
      RESULTS: In total, data were obtained for 28 of 30 patients. The values of K
      before the laryngoscopy were not significantly different between the groups (2
      ng/mL group: 13.1 [8.5-33.1] mmHg/%; 6 ng/mL group: 11.6 [4.3-31.4] mmHg/%;
      P=0.53). After laryngoscopy, K was approximately 2 times greater in the 2 ng/mL
      group than in the 6 ng/mL group (39.0 [13.6-115.9] mmHg/% vs. 19.0 [5.5-85.1]
      mmHg/%, P=0.02). After intubation also, K was approximately 2 times greater in
      the 2 ng/mL group (52.0 [27.7-122.0] mmHg/% vs. 24.3 [7.2-94.9] mmHg/%, P=0.04).
      CONCLUSIONS: The value for arterial stiffness (K) non-proportionally changes in
      response to stimulus intensity; therefore, it has the potential to be used as an
      indicator of nociceptive stimulation intensity.

PMID- 28749096
TI  - Early goal directed therapy by continuous non-invasive hemodynamic monitoring:
      still elusive?

PMID- 28749097
TI  - Lymphoepithelioma-Like Carcinoma of the Breast Mimicking Granulomatous Mastitis-
      Case Report and Review of the Literature
AB  - Lymphoepithelioma-like carcinoma (LELC) of the breast is an exceedingly rare
      variant of mammary cancer. To ourknowledge, only twenty - one cases have been
      reported in the literature. Diagnosis of this type of mammary carcinomamay be
      challenging, owing to its rarity and the histopathological similarity to common
      inflammatory and malignantlesions of the breast mainly granulomatous mastitis,
      medullary carcinoma, pleomorphic lobular carcinoma, lymphomaand other
      hematological malignancies. Our case is the 22nd case of lymphoepithelioma-like
      carcinoma reported in thebreast, presenting with a palpable tender mass in a post
      menopausal female. Her clinical picture had been mistaken forinflammatory
      disease. We present our case, with its detailed clinical history, radiological
      findings, histopathologicaland immune-histochemical findings along with a review
      of the literature. Highlighting this type of tumors may helpin appropriate
      diagnosis. Moreover, studying the behavior of these rare neoplasms is essential
      to expedite treatmentfor this tumor type.

PMID- 28749098
TI  - Association of XRCC2 rs3218536 Polymorphism with Susceptibility of Breast and
      Ovarian Cancer: A Systematic Review and Meta-Analysis
AB  - Background: Previous studies have investigated the association of X-Ray Repair
      Cross-Complementing Group2 (XRCC2) rs3218536 polymorphism with breast and ovarian
      cancer. However, this association remains conflicting.Therefore, we have
      performed the current systematic review and meta-analysis to clarify the
      association betweenXRCC2 rs3218536 polymorphism with risk of breast and ovarian
      cancer. Methods: We conducted a search inPubMed, Google Scholar and ISI Web of
      Science to select relevant studies on the association of XRCC2
      rs3218536polymorphism with breast and ovarian cancer susceptibility. We
      calculated the odds ratios (OR) and 95% confidenceintervals (CI) for five genetic
      contrasts. In addition, a stratified analysis was conducted cancer type,
      ethnicity and HWEstatus. Results: A total of 17 studies with 5694 cases and 6450
      controls for breast cancer and nine case-control studieswith 4464 cases and 6353
      controls for ovarian cancer were identified for the analysis of the association
      with XRCC2rs3218536 polymorphism. The pooled ORs revealed that XRCC2 rs3218536
      polymorphism was associated with breastcancer under the heterozygote contrast (AG
      vs. GG: OR = 0.929, 95% CI = 0.873-0.987, p=0.018) and ovarian cancerunder
      dominant contrast (AA+AG vs. GG: OR = 0.725, 95% CI = 0.537-0.979, p=0.036) in
      the overall population.The stratified analysis indicated a significant
      association of XRCC2 rs3218536 polymorphism with breast and ovariancancer risk
      among Caucasians. Conclusion: Inconsistent with previous meta-analysis, this meta
      analysis shows that theXRCC2 rs3218536 polymorphism was associated with breast
      and ovarian cancer risk in overall population, especiallyamong Caucasians.

PMID- 28749099
TI  - Medical Devices; Immunology and Microbiology Devices; Classification of the
      Assayed Quality Control Material for Clinical Microbiology Assays. Final order.
AB  - The Food and Drug Administration (FDA, Agency, or we) is classifying the assayed
      quality control material for clinical microbiology assays into class II (special
      controls). The special controls that will apply to the device are identified in
      this order and will be part of the codified language for the assayed quality
      control material for clinical microbiology assays' classification. The Agency is
      classifying the device into class II (special controls) to provide a reasonable
      assurance of safety and effectiveness of the device.

PMID- 28749100
TI  - Medical Devices; Cardiovascular Devices; Classification of the Balloon Aortic
      Valvuloplasty Catheter. Final order.
AB  - The Food and Drug Administration (FDA, Agency, or we) is classifying the balloon
      aortic valvuloplasty catheter into class II (special controls). The special
      controls that will apply to the device are identified in this order and will be
      part of the codified language for the balloon aortic valvuloplasty catheter's
      classification. The Agency is classifying the device into class II (special
      controls) to provide a reasonable assurance of safety and effectiveness of the
      device.

PMID- 28749101
TI  - Barriers to Cervical Cancer and Breast Cancer Screening Uptake in Low-Income and
      Middle-Income Countries: A Systematic Review
AB  - Background: Cervical cancer (CCa) and breast cancer (BCa) are the two leading
      cancers in women worldwide.Early detection and education to promote early
      diagnosis and screening of CCa and BCa greatly increases the chancesfor
      successful treatment and survival. Screening uptake for CCa and BCa in low and
      middle - income countries (LMICs)is low, and is consequently failing to prevent
      these diseases. We conducted a systematic review to identify the keybarriers to
      CCa and BCa screening in women in LMICs. Methods: We performed a systematic
      literature search usingOvid MEDLINE, EMBASE, PsycINFO, SCOPUS, CINHAL Plus, and
      Google scholar to retrieve all English languagestudies from inception to 2015.
      This review was done in accordance with the PRISMA-P guidelines. Results: 53
      eligiblestudies, 31 CCa screening studies and 22 BCa screening studies, provided
      information on 81,210 participants. Wefound fewer studies in low-income and lower
      - middle - income countries than in upper - middle - income countries.Lack of
      knowledge about CCa and BCa, and understanding of the role of screening were the
      key barriers to CCa andBCa screening in LMICs. Factors that are opportunities for
      knowledge acquisition, such as level of education, urbanliving, employment
      outside the home, facilitated CCa and BCa screening uptake in women in LMICs.
      Conclusions:Improvements to CCa and BCa screening uptake in LMICs must be
      accompanied by educational interventions whichaim to improve knowledge and
      understanding of CCa and BCa and screening to asymptomatic women. It is
      imperativefor governments and health policy makers in LMICs to implement
      screening programmes, including educationalinterventions, to ensure the
      prevention and early detection of women with CCa and BCa. These programmes
      andpolicies will be an integral part of a comprehensive population-based CCa and
      BCa control framework in LMICs.

PMID- 28749102
TI  - An Exploration of Phytochemicals from Simaroubaceae
AB  - Natural products such as plants, animals and minerals have been the basis of
      treatment of human diseases. Herbalremedies have been used for the treatment of
      many ailments. Many compounds have been derived from the plantspecies mentioned
      in the ancient texts of Indian system of medicine for the treatment of a number
      of ailments. The Rand D thrust in the pharmaceutical sector is focused on
      development of new drugs, innovative/indigenous processesfor known drugs and
      development of plant based drugs through investigation of leads from the
      traditional systems ofmedicine. The family Simaroubaceae is grouped in the order
      Rutales, is known to have a diverse range of secondarymetabolites. Plants from
      this family are used as medicine to cure cancer and many other diseases.
      Isolation of diversechemical compounds from Simaroubaceae on its stem bark, root
      bark and leaves have been reported. In this review,we are analysing with the
      chemical constituents of family Simaroubaceae.

PMID- 28749103
TI  - Decreased Mean Platelet Volume is Associated with Cervical Cancer Development
AB  - Background: Cervical cancer is the most common gynecological malignant disorder
      worldwide. Activated plateletsplay a key role in cancer development and
      progression. Mean platelet volume (MPV) is an early indicator of
      plateletactivation. The aim of the present study was to evaluate MPV levels in
      patients with cervical cancer. Materials andmethods: A total of 181 patients with
      cervical cancer and 181 controls between January 2015 and June 2015 wereincluded
      in the study. Patient characteristics and hematologic test data at initial
      diagnosis were collected and oddsratios (ORs) and 95% confidence intervals (CIs)
      for risk of cervical cancer were calculated using multivariate logisticregression
      analyses across MPV quartiles. Results: MPV levels were decreased in patients
      with cervical cancer comparedwith control subjects. A significant correlation
      between MPV and FIGO stage was found. Moreover, after adjustingfor other risk
      factors, the ORs (95%CIs) for cervical cancer according to MPV quartiles were
      4.450 (1.975-10.026),2.505 (1.206-5.202), 0.573 (0.261-1.259), and 1.000,
      respectively. Conclusions: MPV was found to be independentlyassociated with the
      presence of cervical cancer. Our results suggest that MPV could be potential
      diagnostic screening tool.

PMID- 28749104
TI  - Platelet Distribution Width and Serum Albumin Levels for Discrimination of
      Thyroid Cancer From Benign Thyroid Nodules
AB  - Thyroid cancer is the most rapidly increasing cancer type among women and the
      second among men. Early detectiongreatly improves the prognosis. For this
      purpose, the platelet distribution width (PDW), an early indicator of
      plateletactivation, might be useful. The aim of this study was to investigate the
      ability of PDW and serum albumin levelsindividually or in combination to
      distinguish between thyroid cancer and benign thyroid nodules. A total of 265
      patientswith thyroid cancer and 243 with benign thyroid nodules were included in
      a development set. Then, two groups of130 cases were enrolled in a validation
      set. Patient characteristics and hematologic test data at initial diagnosis
      werecollected. Receiver operating characteristic curves (ROC), area under the
      curve (AUC) values, sensitivity and specificitywere estimated. Albumin levels are
      significantly lower and PDW significantly higher in patients with thyroid
      cancercompared to the benign cases. Moreover, PDW values prominently differed
      among three types of thyroid cancer. Inaddition, the combination of PDW and
      albumin exhibited a significantly larger AUC than either marker alone (p <
      0.001).In conclusion, the combined use of PDW and albumin might be useful in
      distinguishing thyroid cancer from benignthyroid nodules. This promising approach
      could be helpful in early detection of thyroid cancer.

PMID- 28749105
TI  - Compensation for Asbestos-Related Diseases in Japan: Utilization of Standard
      Classifications of Industry and Occupations
AB  - Background: Asbestos-related diseases (ARD) are occupational hazards with high
      mortality rates. To identifyasbestos exposure by previous occupation is the main
      issue for ARD compensation for workers. This study aimedto identify risk groups
      by applying standard classifications of industries and occupations to a national
      database ofcompensated ARD victims in Japan. Methods: We identified occupations
      that carry a risk of asbestos exposureaccording to the International Standard
      Industrial Classification of All Economic Activities (ISIC). ARD compensationdata
      from Japan between 2006 and 2013 were retrieved. Each compensated worker was
      classified by job sectionand group according to the ISIC code. Risk ratios for
      compensation were calculated according to the percentage ofworkers compensated
      because of ARD in each ISIC category. Results: In total, there were 6,916 workers
      with ARDwho received compensation in Japan between 2008 and 2013. ISIC
      classification section F (construction) had thehighest compensated risk ratio of
      6.3. Section C (manufacturing) and section F (construction) had the largest
      numberof compensated workers (2,868 and 3,463, respectively). In the
      manufacturing section C, 9 out of 13 divisions had arisk ratio of more than 1.
      For ISIC divisions in the construction section, construction of buildings
      (division 41) had thehighest number of workers registering claims (2,504).
      Conclusion: ISIC classification of occupations that are at riskof developing ARD
      can be used to identify the actual risk of workers' compensation at the national
      level.

PMID- 28749106
TI  - Bioassay-Guided Isolation and Evaluation of Antiproliferative  Effects of (Z)
      Ethylidene-4, 6-Dimethoxycoumaran-3-One fromPogostemon Quadrifolius (Benth.)
AB  - The aim of the study was to isolate and identify the major cytotoxic principle
      from plant leaves of Pogostemonquadrifolius (Benth.) and evaluate its
      antiproliferative potential against human cancer cells. Plant leaves were
      extractedsequentially with a soxhlet apparatus, using petroleum ether, chloroform
      and methanol solvents. Petroleum ether andchloroform extracts exhibited
      antiproliferative properties against Caco-2, HeLa, THP-1, MCF-7 and Jurkat E6
      1cancercell lines tested, but methanol extracts failed to exhibit such activity.
      The major antiproliferative principle from petroleumether and chloroform extracts
      was isolated with the help of bioassay guided column chromatography. This
      cytotoxiccompound was further analysed by UV, TLC, HPLC, LC-MS, GC-MS and NMR
      analyses and was identified to benovel: (Z)-ethylidene-4,6-dimethoxycoumaran-3
      one (Compound 1). The half-maximal inhibitory concentrations forproliferation
      (IC50) exhibited by compound 1 were 19.4, 23.1, 22.1, 35.9 and 8.32 MUM against
      Caco-2, HeLa, THP-1,MCF-7 and Jurkat E6-1 cancer cell lines, respectively.
      Further experiments revealed that compound 1 triggered theapoptosis mode of cell
      death in cancer cell lines. Thus, the present study allowed isolation and
      identification of anovel cytotoxic natural compound, (Z)-ethylidene-4,6
      dimethoxycoumaran-3-one, from plant leaves of P. quadrifolius(Benth.). Our pre
      clinical study also indicated that compound 1 is particularly active in the acute
      T cell leukemia cellline (Jurkat E6-1) with potential for application as a
      chemotherapeutic agent in the future.

PMID- 28749107
TI  - Content of Spiritual Counselling for Cancer Patients Undergoing Chemotherapy in
      Iran: A Qualitative Content Analysis
AB  - Background: Cancer is one of the leading causes of human death. Besides clinical
      treatment, cancer patients mayneed emotional and spiritual counselling to
      overcome their mental and morale problems. Such counselling sessionshave been
      reported influential by many patients. We aimed to explore the structure of
      spiritual counselling sessionsand their content as one of services provided to
      patients who experience chemotherapy in Iranian hospitals. Methods:Through a
      qualitative content analysis study, we recorded the discussions between a
      counsellor, who was a cleric as well,and cancer cases who were undergoing
      chemotherapy in a hospital in Tehran. The sessions were only recorded if
      thepatient consented to attend at the study. All consideration were taken to
      avoid release of patients' identity. The recordeddiscussions were transcribed
      verbatim and analyzed thematically after each session, until no new theme was
      emerged.Result: Twenty two sessions were held. The patients aged 53 years old on
      average. The content of discussions wereanalyzed along which 165 codes emerged.
      Four general themes or phases were recognized through counseling as (i)history
      Taking (including demographic, disease-related and spiritual history and
      characteristics), (ii) general advice, (iii)spiritual-religious advice, and (iv)
      dealing with patients' spiritual or religious ambiguities and paradoxes.
      Conclusion:Counselling of cancer patients needs special and in depth knowledge on
      spiritual and religious issues. The counsellorshould be able to motivate
      patients, among whom many are disappointed, to follow the curative instructions
      well andstay hopeful about their treatment and life. Exploring and understanding
      what happens during a spiritual counsellingsession can counselling to the
      conformity and standardization of such interventions.

PMID- 28749108
TI  - SNP and Haplotype Analysis of Vascular Endothelial Growth Factor (VEGF) Gene in
      Lung Cancer Patients of Kashmir
AB  - Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis
      involving tumor growth andmetastasis. In this large case-control study, we
      investigated whether functional polymorphisms (+405C>G, +936C>T)in the VEGF gene
      are associated with the risk of lung cancer. The study investigates the
      association between variants ofVEGF gene and lung cancer. We performed single
      nucleotide polymorphism (SNP), haplotype and linkage disequilibriumstudies on 100
      patients and 128 healthy controls with 2 SNPs in the VEGF gene. The results were
      analyzed usinglogistic regression models, adjusted for age and sex. No
      Significant association was detected between individual SNPsand lung cancer using
      all the models of inheritance (codominant, dominant, recessive, over dominant and
      additive)for finding an association between genotypes and the cancer risk. The P
      values obtained for two markers were nonsignificant(P>0.05). Haplotype analysis
      produced additional support for the non-association of individual haplotypes/all
      haplotypes with the cancer risk (Global association P=0.56). Our findings suggest
      the non-involvement of geneticvariants (+405C>G, +936C>T) of the VEGF gene in the
      etiology of lung cancer.

PMID- 28749109
TI  - XPG Asp1104His, XRCC2 Rs3218536 A/G and RAD51 135G/C Gene Polymorphisms and
      Colorectal Cancer Risk: A Meta-Analysis
AB  - Background: DNA repair mechanisms are crucial for sustaining DNA integrity and
      preventing carcinogenesis. Thexeroderma pigmentosum group G (XPG), X-ray repair
      cross complementing group 2 (XRCC2) and RAD51 are candidategenes for DNA repair
      pathways. Methods: We performed a meta-analysis of 26 studies that assessed the
      impact of XPGAsp1104His, XRCC2 rs3218536 A/G and RAD51 135G/C polymorphisms on
      colorectal cancer (CRC) risk. This studyincluded 10288 CRC patients and 11885
      controls, and odds ratio (OR) with its 95% confidence interval (CI) were usedto
      calculate the strength of association. Results: The results of overall meta
      analysis suggested an association betweenthe XPG Asp1104His polymorphism and CRC
      susceptibility in allele (OR=1.06; 95% CI=1.01-1.12) and heterozygotemodel
      (OR=1.16; 95%CI=1.02-1.31). In the subgroup analysis based on ethnicity and
      source of control, we foundsignificantly increased CRC cancer risk in Asians
      (OR=1.12, 95%CI=1.04-1.21) and in hospital-based (OR=1.22,95%CI=1.08-1.38)
      populations. Moreover, the RAD51 135 G/C polymorphism increased the risk of CRC
      in total usingallele (OR=1.21) and recessive models (OR=1.62). However, XRCC2
      rs3218536 A/G was not associated with the riskof CRC in total or in subgroups.
      Conclusions: According to the results of our meta-analysis, the XPG Asp1104His
      andRAD51 135 G/C polymorphisms might influence colorectal cancer risk.

PMID- 28749110
TI  - Haplotype Analysis of MDR1 and Risk for Cervical Cancer in Northeastern Thailand
AB  - Objective: The aim of this study was to investigate the association between
      genotype and haplotype of MDR1(C1236T, G2677T/A and C3435T) and the risk for
      cervical cancer in Northeastern Thai women. Methods: Anage-matched case-control
      study involving squamous cell cervical cancer (SCCA) patients (n=204) and healthy
      controls(n=204) was enrolled for MDR1 genotyping by real-time PCR method.
      Results: The genotype distribution of MDR1 inboth patients and controls was not
      significantly different (p>0.05). The haplotype analysis showed that T-T-T was
      themost common haplotype in this population. Significantly increased risk of
      cervical cancer was observed in carriers ofT-T-C and C-G-T haplotypes with ORs of
      1.86 (95%CI=1.02-3.39, p=0.0416) and 2.00 (95%CI=1.18-3.40,
      p=0.0140),respectively. Analysis of 2677-3435 haplotype showed increased risk for
      cervical cancer in G-T (OR=1.55; 95%CI=1.12-2.13, p=0.0432) and T-C (OR=1.91;
      95%CI=1.05-3.47, p=0.0325). Conclusion: The results provide evidencethat
      haplotype of MDR1 may be an important risk factor for cervical cancer development
      in Northeastern Thai women.

PMID- 28749111
TI  - Syncope in pediatric patients: a practical approach to differential diagnosis and
      management in the emergency department [digest].
AB  - Syncope is a condition that is often seen in the emergency department. Most
      syncope is benign, but it can be a symptom of a life-threatening condition. While
      syncope often requires an extensive workup in adults, in the pediatric
      population, critical questioning and simple, noninvasive testing is usually
      sufficient to exclude significant or life-threatening causes. For low-risk
      patients, resource-intensive workups are rarely diagnostic, and add significant
      cost to medical care. This issue will highlight critical diseases that cause
      syncope, identify high-risk "red flags," and enable the emergency clinician to
      develop a cost-effective, minimally invasive algorithm for the diagnosis and
      treatment of pediatric syncope. [Points & Pearls is a digest of Pediatric
      Emergency Medicine Practice].

PMID- 28749112
TI  - Serum Procalcitonin Predicts Anastomotic Leaks in Colorectal Surgery
AB  - Background: Anastomotic leaks in colorectal surgery results in a high morbidity
      and mortality rate. Serumprocalcitonin levels is known as a sensitive and
      specific marker of sepsis and could be use as a marker for early detectionof a
      leak allowing early intervention. It may help a clinician decide to perform a CT
      scan even earlier especiallywhen the diagnosis of a leak is uncertain. The aim of
      this study is to determine whether serum procalcitonin is a goodpredictor of
      anastomotic leak in colorectal surgery. Methodology: Between July 2014 until
      October 2015, 70 patientsundergoing colorectal surgery were prospectively
      analyzed in a single-center tertiary teaching hospital. Demographicand surgical
      data were obtained. Serum procalcitonin was taken before surgery and at day 3 (72
      hours) postoperatively.During the postoperative period, the patients were
      observed in the ward for features of anastomotic leak and if present,it was
      managed accordingly. The primary outcome was to prospectively determine an
      association between serumprocalcitonin levels and an anastomotic leak in patients
      who underwent colorectal surgery with a primary anastomosis.Result: The rate of
      anastomotic leak was 4.5% (3 patients) with a mortality rate of 4.3% (3
      patients). A rise in serumprocalcitonin was statistically significant among
      patients with anastomotic leak. The optimal procalcitonin cut-offlevel at
      postoperative day 3 was 5.27 ng/mL, resulting in 100% sensitivity, 85%
      specificity, 23% positive predictivevalue and 100% negative predictive value.
      Nevertheless, none of the variables showed statistical significance with
      ananastomotic leak. Conclusion: Procalcitonin is a reliable biochemical marker to
      help diagnose anastomotic leak incolorectal surgery. Our study has shown that a
      level of 5 times beyond normal is statistically significant and a value ofmore
      than 5.27 ng/mL is confirmatory of a leak.

PMID- 28749113
TI  - Increased Tumour Infiltration of CD4+ and CD8+ T-Lymphocytes in Patients with
      Triple Negative Breast Cancer Suggests Susceptibility to Immune Therapy
AB  - Background: Patients with triple negative breast cancer (TNBC) have limited
      therapeutic options, largely becausethe complex tumour environment is not well
      characterized. These patients are potential, but largely un-fathomed,candidates
      for immunotherapy. It is therefore highly relevant to characterize leukocyte
      complexity in TNBCs. Objective:To investigate leukocyte complexity in tumour
      environment of patients with TNBCs. Materials and methods: A totalof 104
      consecutive breast cancer patients undergoing mastectomy were recruited in the
      study after ethical approval.Clinico-pathological parameters were recorded and H
      and E staining was performed to investigate tumour morphology.Receptor status was
      investigated using antibodies against ER, PgR and Her-2, and patients were
      classified as havingTNBC or non-TNBC tumours (including Luminal A, Luminal B and
      Her2 overexpressing tumours). Immune-cellinfiltration was investigated using
      special stains and antibodies: alpha-CD3 (T-lymphocytes), alpha-CD20 (B
      lymphocytes),alpha-CD4 (helper T-lymphocytes) and alpha-CD8 (cytotoxic T
      lymphocytes). Immune cell densities were quantified as cell/mm2 using the CAP
      guidelines. Results: Of the 104 breast cancer patients investigated, a total of
      27 (26%) had TNBCand 77(74%) non-TNBC. Patients with TNBC showed significantly
      increased tumour infiltration of lymphocytes (Tand B-lymphocytes) compared to the
      patients with non-TNBC, while myelocytic infiltration was not
      significantlydifferent in the two groups. Within the TNBC group, infiltration of
      T-lymphocytes (equal densities of CD4+ and CD8+T-lymphocytes) was significantly
      higher compared to B-lymphocytes. Conclusion: Patients with TNBC show
      increasedlymphocytic infiltration (more T-lymphocytes compared to B-lymphocytes).
      This suggests higher immunogenicity ofTNBCs and may indicate a higher
      responsiveness of these cancers to immunotherapy.

PMID- 28749114
TI  - Characteristics and Outcomes of Patients with Hematological Malignancies Admitted
      for Intensive Care - a Single Centre Experience
AB  - Background and Purpose: Patients with hematological malignancies admitted to an
      intensive care unit (ICU)generally have a high mortality rate. The aim of our
      study was to assess the characteristics and outcomes of suchpatients and to
      identify factors predicting ICU mortality. Material and Methods: This
      retrospective chart review wasconducted in the intensive care unit (ICU) of
      Shaukat Khanum Memorial Cancer Hospital and Research Centre over aperiod of 5
      years, from January 2010 to January 2015. Results: Characteristics :A total of
      213 patients were includedin this study. There were 150 (70.4%) males and 63
      (29.6%) females with the median age of 36 years (18-88 years).Main diagnosis was
      non- Hodgkin lymphoma in 127 (59.6%) followed by Hodgkin's disease in 27 (12.7%)
      and acutemyeloid leukemia in 16 (7.5%). Most of the patients 154 (72.3%) were on
      active chemotherapy at the time of admissionto ICU, while 28 patients (13.1%) had
      newly diagnosed disease and 22 (10.3%) featured either relapsed or
      progressivedisease. The most common reason for admission to ICU was a combination
      of respiratory failure with septic shock(29.6%) followed by septic shock alone
      (19.7%) and acute respiratory failure (13.1%). Other causes included acuterenal
      failure, alone (7.5%) or in combination with respiratory or circulatory collapse
      (10.8%) and central nervoussystem involvement (5.6%). The majority of admissions
      to ICU occurred between days one and five of admission toa ward (46.5%, n=99)
      whereas 49 (23%) were taken directly to the ICU. Mainstay of treatment in 38.5%
      of patientsincluded both invasive ventilation and vasopressor support along with
      other supportive care like fluids and antibiotics.23.5% received only supportive
      management. Duration of stay for 150 (70.4%) patients was between one to
      sevendays. Outcomes: A total of 119 (55.9 %) patients expired while in ICU, while
      14 (6.6%) died in hospital after beingtransferred out of ICU. ICU survival was
      44.1% whereas hospital survival was 37.5%. After discharge from hospital ina
      stable condition, 18 (8.5%) patients were lost to follow up and 62 (29%) patients
      were alive after thirty days. A totalof 33 (15.4 %) of patients survived for at
      least one year after ICU admission. Some 21 (9.8%) are still alive and
      healthyafter a minimum median follow up of one and a half years. Predictors of
      Mortality: Overall, mechanical ventilationwas required in 61% of patients. Out of
      the patients who expired, 92.4% required intubation, in contrast to 21.3%
      forthose who survived the ICU stay. Involvement of three or more organs was
      apparent in 12.8% of improved patients and70.6% of those who died during ICU
      stay. Neutropenia did not appear to be a major discriminatory factor, with 33%
      ofimproved and 42.9% of expired patients being neutropenic at the time of
      admission to ICU. The majority of patientsfrom both the improved and expired
      group required intubation and vasopressors from day one onwards.
      Conclusions:Admission of patients with hematological malignancies to the
      intensive care unit is associated with poor outcome andhigh mortality.
      Identifying the patients who can benefit from aggressive care and prolonged ICU
      support is importantespecially when it comes to countries like ours with limited
      resources and major financial restraints. Multi-organ damageand requirement of
      invasive ventilation are two main predictors of increased mortality. Neutropenia
      is also associatedwith adverse outcome; however, the difference is not as
      significant as for the other two factors.

PMID- 28749115
TI  - Deregulated HOXB7 expression predicts poor prognosis of patients with
      malignancies of digestive system.
AB  - INTRODUCTION: Numerous studies have investigated the relationship between
      deregulated HOXB7 expression with the clinical outcome in patients with digestive
      stem cancers, HOXB7 has showed negative impacts but with varying levels. We aimed
      to comprehensively evaluate the prediction and prognostic value of HOXB7 in
      digestive stem cancers. EVIDENCE ACQUISITION: Electronic databases updated to
      December 1, 2016 were retrieved to collect relevant eligible studies to
      quantitatively explore the potential roles of HOXB7 as a prognostic indicator in
      digestive system cancers. EVIDENCE SYNTHESIS: A total of 9 studies (n = 1298
      patients) was included in this synthetical meta-analysis. The pooled hazard
      ratios suggested that high expression of HOXB7 protein was associated with poor
      prognosis of OS in patients with digestive system cancers (HR = 1.97, 95% CI:
      1.65-2.28, p= 0.000), and HOXB7 protein could act as an independent prognostic
      factor for predicting OS of patients with digestive system cancers (HR: 2.02, 95%
      CI: 1.69-2.36, p = 0.000). Statistical significance was also observed in subgroup
      meta-analysis based on the cancer type, histology type, country, sample size and
      publication date. Furthermore, we examined the correlations between HOXB7 protein
      and clinicopathological features. It showed that altered expression of HOXB7
      protein was correlated with tumor invasion (p = 0.000), lymph node status (p =
      0.000), distant metastasis (p = 0.001) and TNM stage (p = 0.000). However, the
      expression of HOXB7 protein was not associated with age (p = 0.64), gender (p =
      0.40) or levels of differentiation (p = 0.19). CONCLUSIONS: High expression of
      HOXB7 protein was associated with poor prognosis of patients with digestive
      system cancers, as well as clinicopathologic characteristics, including the tumor
      invasion, lymph node status, distant metastasis and TNM stage. The expression of
      HOXB7 protein was not associated with age, gender or levels of differentiation.
      HOXB7 protein expression level in tumor tissue might serve as a novel prognostic
      marker for digestive system cancers.

PMID- 28749116
TI  - Autologous dermal patch in immediate prosthetic breast reconstruction.

PMID- 28749117
TI  - Roux-en-Y gastric bypass versus sleeve gastrectomy: risks and benefits.
AB  - INTRODUCTION: Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG) are the
      most commonly performed metabolic surgeries and are highly effective for the
      treatment of obesity and related comorbidities. In this narrative review, recent
      studies of at least two years of follow-up directly comparing outcomes between GB
      and SG are reviewed to assess the efficacy of each procedure in weight loss and
      diabetes remission, as well as resulting quality of life (QoL) assessment and
      micronutrient deficiencies. EVIDENCE ACQUISITION: A systematic search of the
      literature of PubMed using MeSH terms and key words was performed. EVIDENCE
      SYNTHESIS: Forty recent studies comparing GB and SG including 208,556 patients
      are included in this narrative review. Most studies demonstrate significantly
      greater weight loss after GB compared to SG. There is some evidence that GB may
      lead to greater proportion of remission of diabetes mellitus (DM), but the
      majority of studies found no significant difference at longer follow-up. There is
      some evidence of greater rates of vitamin D and B12 deficiencies following GB.
      There were no significant differences in QoL assessments between SG and GB.
      CONCLUSIONS: A review of moderate and long-term studies directly comparing SG and
      GB suggests a greater degree of weight loss with GB. There is some but limited
      evidence the GB is more likely to induce DM remission, while increasing the risk
      of specific micronutrient deficiencies.

PMID- 28749118
TI  - Prevalence of Human Papillomavirus Infection in Breast Cancer Cells from Thai
      Women
AB  - Breast cancer is the leading female cancer worldwide and is the most frequently
      diagnosed in Thai women. Itspotential etiologic has not been clearly identified.
      Several recent reports could detect human papillomavirus (HPV)infection in breast
      cancer or benign breast lesions. HPV infection considered suggests being one of
      many risk factorsfor cancer development. The aim of this study was to determine
      the frequency of HPV infection in both breast cancerand benign breast
      lesion/tumor tissues. Seven hundred samples from Thai women were collected during
      2013-2015and statistically correlation between HPV infection, sociodemographic
      and histopathological parameters were alsoanalyzed. HPV DNA detection and
      genotyping were performed by polymerase chain reaction and enzyme
      immunoassay,respectively. The results demonstrated that mean age of the patients
      were 41.76+/-12.53 years and 52.73+/-11.68 yearsfor benign breast lesions/tumor
      and breast cancer samples, respectively. HPV DNA was detected in 25/700
      (3.57%)samples, in which 10/350 (2.857%) from benign breast lesion/tumor samples
      and 15/350 (4.285%) from breast cancersamples. HPV 16 is the predominant types of
      this study, follow by HPV 33, 18, 35, 52. Most of HPV type detectionsamples
      belong to the high risk types, except 1/25 sample could be detected low risk
      type; HPV 6 which was presentedas co-infection with the other high risk type.
      From sociodemographic and histopathological correlation analysis, allof studied
      parameters such as breast cancer history, hormone receptors status etc. did not
      show statistically significantcorrelated with HPV infection (P>0.05). In
      conclusion, the low frequency detection in this study suggests that HPVdid not
      play the main important role for breast cancer development and represented highly
      controversial, but it maybe causative agents of only a relative small proportion
      of all breast cancer or non-malignant breast lesion and it is theinteresting data
      for further study in virus-associated cancer.

PMID- 28749119
TI  - Antitumor Exopolysaccharides Derived from Novel Marine Bacillus: Isolation,
      Characterization Aspect and Biological Activity
AB  - Objective: Exopolysaccharides gained attention as new source for cancer treatment
      as recent treatments cause sideeffects and multidrug resistance. Polysaccharides
      containing sulfur and uronic acids exhibited antioxidant activity, byrestoring
      cell redox regulation, thus inhibiting cell proliferation and cancer formation.
      Following this context, our studywas performed to assess the cytotoxic activity
      of exopolysaccharides produced by novel Egyptian marine bacterialstrains on HepG2
      cells. Methods: Bacteria were isolated, purified and cultured through routine
      microbiologicaltechniques. 16S rRNA gene amplification and sequence analyses,
      Fourier Transform Infra-red (FTIR), Identificationof monosugars by HPLC molecular
      weight estimation, sulfur content determination and neutral red uptake assay
      wereutilized. Results: BLAST showed that the isolates were related to the
      Bacillus sp. FTIR analysis indicated that thefour EPSs under study contained
      sulfur as substituent functional group but with different percentage in each
      EPS.The highest sulfur percentage (46%) appeared in the EPS-6 that was produced
      by Bacillus flexus isolated from theMediterranean Sea. HPLC showed that EPSs
      contained uronic acids which appeared as glucuronic and galacturonic acidin the
      low molecular weight EPS-6 (4.296*104 g mol-1). Arabinose appeared besides the
      glucuronic and galacturonicacid residues. EPS-6 showed the highest cytotoxicity,
      IC50 (218 MUg ml-1) which could be correlated to the presence ofsulfure and
      uronic acids in its structure. Conclusion: The novel Firmicutes from the Egyptian
      saline habitat producedEPSs of cytotoxic activity on hepatocellular carcinoma.

PMID- 28749120
TI  - Effects of Tobacco Habits on the Polymorphism of NFKB1 and NFKB1A Gene of Head
      and Neck Squamous Cell Carcinoma in Indian Population
AB  - Background: Polymorphism of NFKB1 and NFKB1A are highly associated with cancer.
      We have assessedpolymorphism in the promoter region of NFKB1 -94 del/ins ATTG
      (rs28362491) and NFKB1A -826 C/T (rs2233406)with the risk of HNSCC in Indian
      population. Methods: Polymerase chain reaction-restriction fragment
      lengthpolymorphism (PCR-RFLP) method was used for the genotyping NFKB1 -94
      del/ins ATTG and NFKB1A -826 C/T.Sequencing was done to validate the results of
      PCR-RFLP. Statistical analysis of data was done by Stata/SE-14.0software.
      Results: ins/ins genotype was observed to be a risk factor of HNSCC as compared
      del/del genotype of NFKB1-94 ATTG. Interactive effects of smoking and chewing on
      ins/ins genotype showed 13.96 and 10.92 fold increasedrisk of HNSCC. NFKB1A -826
      C/T polymorphism, TT genotype showed no association with the risk of HNSCC
      ascompared to wild type CC genotype. Conclusion: Our results showed NFKB1 -94
      del/ins ATTG with smoking andtobacco chewing may increase the risk of HNSCC while
      NFKB1A -826 C/T plays a protective role in Indian population.

PMID- 28749121
TI  - Diphtheria, pertussis, and tetanus: evidence-based management of pediatric
      patients in the emergency department
AB  - Diphtheria, pertussis, and tetanus are potentially deadly bacterial infections
      that are largely preventable through vaccination, though they remain in the
      population. This issue reviews the epidemiology, pathophysiology, diagnosis, and
      current recommended emergency management of these conditions. Disease-specific
      medications, as well as treatment of the secondary complications, are examined in
      light of the best current evidence. Resources include obtaining diphtheria
      antitoxin from the United States Centers for Disease Control and Prevention and
      best-practice recommendations with regard to testing, involvement of government
      health agencies, isolation of the patient, and identification and treatment of
      close contacts. Most importantly, issues regarding vaccination and prevention are
      highlighted.

PMID- 28749122
TI  - Tobacco Use and Effects of Professional Advice on Smoking Cessation among Youth
      in India
AB  - Objective: Healthcare professionals and addiction programs play important roles
      in tobacco use prevention andcessation activities. In this study, we analyzed the
      prevalence of tobacco use and the impact of smoking cessation advicethrough
      programs/professionals among a nationally representative sample of youth in
      India. Methods: The data wereobtained from the Global Youth Tobacco Survey (GYTS)
      2009 dataset from a nationally representative school basedsurvey of 8th to 10th
      grade students in India (n=14,543). Professional or provider advice for smoking
      cessation wasanalyzed with reference to quitting smoking. Descriptive analysis
      was performed for tobacco and smoking prevalenceand the types of tobacco products
      used. Logistic regression was employed to assess any associations between
      professionalor program advice and quitting smoking. Results: The overall
      prevalence of current tobacco use was 13.5%. About 76%were never tobacco users
      and 9.3% were former tobacco users. The prevalences of smoking, smokeless tobacco
      andpoly tobacco use among current tobacco users were 35.1%, 43.3% and 21.5%
      respectively. Among the never smokers,80% were weakly and 20% were strongly
      susceptible. Recipients of advice from a program or professional showedhigher
      odds (OR=5.3) of quitting smoking. Conclusion: Professional and program advice to
      quit smoking is veryeffective for youth in India. More programs and healthcare
      professionals must be employed to prevent and encourageyouth to abstain from the
      use of tobacco.

PMID- 28749123
TI  - Infectious complications related to external ventricular shunt. Incidence and
      risk factors.
AB  - OBJECTIVE: Infectious complications related to external ventricular shunt
      (ICREVS) are a main problem in neurocritical intensive care units (ICU). The aim
      of the review is to assess the incidence of ICREVS and to analyse factors
      involved. METHODS: Retrospective analysis, adult polyvalent ICU in a third level
      reference hospital. Patients carrying external ventricular shunt (DVE) were
      included. Those patients with central nervous system infection diagnosed prior
      DVE placement were excluded. RESULTS: 87 patients were included with 106 DVE.
      Most common admittance diagnosis was subarachnoid haemorrhage (49.4%). 31
      patients with 32 DVE developed an ICREVS. Infection rate is 19.5 per 1000 days of
      shunt for ICREVS and 14 per 1000 days for ventriculitis. 31.6% of the patients
      developed ICREVS and 25.3% ventriculitis. Patients who developed ICREVS presented
      higher shunt manipulations (2.0 +/- 0.6 vs. 3.26 +/- 1.02, p=0.02), shunt
      repositioning (0.1 +/- 0.1 vs. 0.2 +/- 0.1) and ICU and hospital stay (29.8 +/-
      4.9 vs 49.8 +/- 5.2, p<0.01 y 67.4 +/- 18.8 vs. 108.9 +/- 30.2, p=0.02. Those DVE
      with ICREVS were placed for longer not only at infection diagnosis but also at
      removal (12.6 +/- 2.1 vs. 18.3 +/- 3.6 and 12.6 +/- 2.1 vs. 30.4 +/- 7.3 days,
      p<0.01). No difference in mortality was found. CONCLUSIONS: One out of three
      patients with a DVE develops an infection. The risk factors are the number of
      manipulations, repositioning and the permanency days. Patients with ICREVS had a
      longer ICU and hospital average stay without an increase in mortality.

PMID- 28749124
TI  - Urinary tract infection in the oldest old: a work overload for the microbiology
      laboratory.

PMID- 28749125
TI  - [Keratitis by Nocardia farcinica in immunocompetent patient. Description of the
      first case in Spain].

PMID- 28749126
TI  - [Micromunidad: specialized microbiology divulgation podcast (2015-2016)].

PMID- 28749127
TI  - Fuzzy-C-Means Clustering Based Segmentation and CNN-Classification for Accurate
      Segmentation of Lung Nodules
AB  - Objective: Accurate segmentation of abnormal and healthy lungs is very crucial
      for a steadfast computer-aideddisease diagnostics. Methods: For this purpose a
      stack of chest CT scans are processed. In this paper, novel methods areproposed
      for segmentation of the multimodal grayscale lung CT scan. In the conventional
      methods using Markov-GibbsRandom Field (MGRF) model the required regions of
      interest (ROI) are identified. Result: The results of proposed FCMand CNN based
      process are compared with the results obtained from the conventional method using
      MGRF model.The results illustrate that the proposed method can able to segment
      the various kinds of complex multimodal medicalimages precisely. Conclusion:
      However, in this paper, to obtain an exact boundary of the regions, every
      empiricaldispersion of the image is computed by Fuzzy C-Means Clustering
      segmentation. A classification process based onthe Convolutional Neural Network
      (CNN) classifier is accomplished to distinguish the normal tissue and the
      abnormaltissue. The experimental evaluation is done using the Interstitial Lung
      Disease (ILD) database.

PMID- 28749128
TI  - Distribution Characteristics of Human Papillomavirus Infection: A Study Based on
      Data from Physical Examination
AB  - Objective: Human papillomavirus (HPV) is the primary cause of cervical cancer.
      The purpose of this study wasto investigate the prevalence and type distribution
      of HPV DNA positive in women undergoing routine physicalexamination. Methods:
      2,452 women were enrolled between March and November 2013. Participants were
      testedfor 23 HPV types using polymerase chain reaction (PCR) and reverse dot blot
      hybridization. HPV DNA detectionprevalence was estimated in different age groups.
      Results: Mean age (SD) of study participants was 47.7 (9.8) years.Overall HPV
      positive prevalence was 18.9% (463/2452), and 22 out of 23 known subtypes were
      detected. Single HPVsubtype prevalence of infection was 14.4%, and multiple
      prevalence of infection was 4.5%. The prevalence of HPVDNA in different age
      groups (20-29, 30-39, 40-49, 50-59, 60-69, >=70) were 9.3%, 15.6%, 17.1%, 22.1%,
      23.0% and20.0%, respectively. HPV 52 was the most prevalent HPV type, followed by
      HPV 58, 53, 16 and 68, in descending orderof prevalence. The top five low-risk
      types of HPV were (in descending order): HPV81, 43, 6, 42 and 11.
      Conclusions:Overall HPV DNA detection prevalence increased significantly with
      increasing age. Concerning high-risk HPV types,HPV 52, 58, 53, 16 and 51 were the
      most common in the study.

PMID- 28749129
TI  - Atomic Layer Deposited Lithium Silicates as Solid-State Electrolytes for All
      Solid-State Batteries.
AB  - Development of solid-state electrolyte (SSE) thin films is a key toward the
      fabrication of all-solid-state batteries (ASSBs). However, it is challenging for
      conventional deposition techniques to deposit uniform and conformal SSE thin
      films in a well-controlled fashion. In this study, atomic layer deposition (ALD)
      was used to fabricate lithium silicate thin films as a potential SSE for ASSBs.
      Lithium silicates thin films were deposited by combining ALD Li2O and SiO2
      subcycles using lithium tert-butoxide, tetraethylorthosilane, and H2O as
      precursors. Uniform and self-limiting growth was achieved at temperatures between
      225 and 300  degrees C. X-ray absorption spectroscopy analysis disclosed that the
      as-deposited lithium silicates were composed of SiO4 tetrahedron structure and
      lithium oxide as the network modifier. X-ray photoelectron spectroscopy confirmed
      the chemical states of Li in the thin films were the same with that in standard
      lithium silicate. With one to one subcycle of Li2O and SiO2 the thin films had a
      composition close to Li4SiO4 whereas one more subcycle of Li2O delivered a higher
      lithium content. The lithium silicate thin film prepared at 250  degrees C
      exhibited an ionic conductivity of 1.45* 10-6 S cm-1 at 373 K. The high ionic
      conductivity of lithium silicate was due to the higher lithium concentration and
      lower activation energy.

PMID- 28749130
TI  - Fluorination of Boron-Doped Diamond Film Electrodes for Minimization of
      Perchlorate Formation.
AB  - This research investigated the effects of surface fluorination on both rates of
      organic compound oxidation (phenol and terephthalic acid (TA)) and ClO4-
      formation at boron-doped diamond (BDD) film anodes at 22  degrees C. Different
      fluorination methods (i.e., electrochemical oxidation with perfluorooctanoic acid
      (PFOA), radio frequency plasma, and silanization) were used to incorporate
      fluorinated moieties on the BDD surface, which was confirmed by X-ray
      photoelectron spectroscopy (XPS). The silanization method was found to be the
      most effective fluorination method using a 1H,1H,2H,2H
      perfluorodecyltrichlorosilane precursor to form a self-assembled monolayer (SAM)
      on the oxygenated BDD surface. The ClO4- formation decreased from rates of 0.45
      +/- 0.03 mmol m-2 min-1 during 1 mM NaClO3 oxidation and 0.28 +/- 0.01 mmol m-2
      min-1 during 10 mM NaCl oxidation on the BDD electrode to below detectable levels
      (<0.12 MUmoles m-2 min-1) for the BDD electrode functionalized by a 1H,1H,2H,2H
      perfluorodecyltrichlorosilane SAM. These decreases in rates corresponded to 99.94
      and 99.85% decreases in selectivity for ClO4- formation during the electrolysis
      of 10 mM NaCl and 1 mM NaClO3 electrolytes, respectively. By contrast, the
      oxidation rates of phenol were reduced by only 16.3% in the NaCl electrolyte and
      61% in a nonreactive 0.1 M KH2PO4 electrolyte. Cyclic voltammetry with Fe(CN)63
      /4- and Fe3+/2+ redox couples indicated that the long fluorinated chains created
      a blocking layer on the BDD surface that inhibited charge transfer via steric
      hindrance and hydrophobic effects. The surface coverages and thicknesses of the
      fluorinated films controlled the charge transfer rates, which was confirmed by
      estimates of film thicknesses using XPS and density functional theory
      simulations. The aliphatic silanized electrode also showed very high stability
      during OH* production. Perchlorate formation rates were below the detection limit
      (<0.12 MUmoles m-2 min-1) for up to 10 consecutive NaClO3 oxidation experiments.

PMID- 28749132
TI  - Universal Ratiometric Photoelectrochemical Bioassay with Target-Nucleotide
      Transduction-Amplification and Electron-Transfer Tunneling Distance Regulation
      Strategies for Ultrasensitive Determination of microRNA in Cells.
AB  - A universal ratiometric photoelectrochemical (PEC) bioassay, which could be
      readily expanded for ultrasensitive determination of various targets in complex
      biological matrixes, was established by coupling a target-nucleotide transduction
      amplification with DNA nanomachine mediated electron-transfer tunneling distance
      regulation strategies. With the help of target-nucleotide transduction
      amplification strategy, the one input target signal could be transducted to
      corresponding multiple output DNA signals by nucleotide specific recognition
      technology, simultaneously leading to an efficient signal amplification for
      target. Then the output DNA could initiate the formation of four-way junction DNA
      nanomachine through binding-induced combination, by which the electron-transfer
      tunneling distance between photoactive materials and sensing interface could be
      regulated, simultaneously resulting an enhanced photocurrent signal from
      SiO2@methylene blue (SiO2@MB) as wavelength-selective photoactive material in
      close proximity to sensing interface and a reduced photocurrent signal from
      another wavelength-selective photoactive material CdS quantum dots (CdS QDs) away
      from sensing interface for photocurrent signal ratio calculation. Using microRNA
      141 (miRNA-141) as target model, the constructed biosensor demonstrated favorable
      accuracy and excellent sensitivity down to the femtomolar level. Impressively,
      the proposed assay overcame the heavy dependence of target on photoactive
      materials in current ratiometric PEC assay and demonstrated admirably universal
      applicability for determination of various targets such as metal ions, miRNAs,
      DNAs, and proteins by merely two different photoactive materials (SiO2@MB and CdS
      QDs), paving the way to application of universal ratiometric PEC assay in
      environmental tests, clinical diagnosis, and other related subjects.

PMID- 28749131
TI  - Lysine Deacetylases Exhibit Distinct Changes in Activity Profiles Due to
      Fluorophore Conjugation of Substrates.
AB  - Lysine deacetylases (KDACs) are enzymes that reverse the post-translational
      modification of lysine acetylation. Thousands of potential substrates, acetylated
      protein sequences, have been identified in mammalian cells. Properly regulated
      acetylation and deacetylation have been linked to many biological processes,
      while aberrant KDAC activity has also been linked to numerous diseases.
      Commercially available peptide substrates that are conjugated to fluorescent dye
      molecules, such as 7-amino-4-methylcoumarin (AMC), are commonly used to monitor
      deacetylation in studies addressing both substrate specificity and small molecule
      modulators of activity. Here, we have compared the activity of several KDACs,
      representing all major classes of KDACs, with substrates in the presence and
      absence of AMC as well as peptides for which tryptophan has been substituted for
      AMC. Our results unequivocally demonstrate that AMC has a significant effect on
      activity for all KDACs tested. Furthermore, in neither the nature of the effect
      nor the magnitude is consistent across KDACs, making it impossible to predict the
      effect of AMC on a particular enzyme-substrate pair. AMC did not affect
      acetyllysine preference in a multiply acetylated substrate. In contrast, AMC
      significantly enhanced KDAC6 substrate affinity, greatly reduced Sirt1 activity,
      eliminated the substrate sequence specificity of KDAC4, and had no consistent
      effect with KDAC8 substrates. These results indicate that profiling of KDAC
      activity with labeled peptides is unlikely to produce biologically relevant data.

PMID- 28749133
TI  - Two-Dimensional Lead(II) Halide-Based Hybrid Perovskites Templated by Acene
      Alkylamines: Crystal Structures, Optical Properties, and Piezoelectricity.
AB  - A series of two-dimensional (2D) hybrid organic-inorganic perovskite (HOIP)
      crystals, based on acene alkylamine cations (i.e., phenylmethylammonium (PMA), 2
      phenylethylammonium (PEA), 1-(2-naphthyl)methanammonium (NMA), and 2-(2
      naphthyl)ethanammonium (NEA)) and lead(II) halide (i.e., PbX42-, X = Cl, Br, and
      I) frameworks, and their corresponding thin films were fabricated and examined
      for structure-property relationship. Several new or redetermined crystal
      structures are reported, including those for (NEA)2PbI4, (NEA)2PbBr4,
      (NMA)2PbBr4, (PMA)2PbBr4, and (PEA)2PbI4. Non-centrosymmetric structures from
      among these 2D HOIPs were confirmed by piezoresponse force microscopy-especially
      noteworthy is the structure of (PMA)2PbBr4, which was previously reported as
      centrosymmetric. Examination of the impact of organic cation and inorganic layer
      choice on the exciton absorption/emission properties, among the set of compounds
      considered, reveals that perovskite layer distortion (i.e., Pb-I-Pb bond angle
      between adjacent PbI6 octahedra) has a more global effect on the exciton
      properties than octahedral distortion (i.e., variation of I-Pb-I bond angles and
      discrepancy among Pb-I bond lengths within each PbI6 octahedron). In addition to
      the characteristic sharp exciton emission for each perovskite, (PMA)2PbCl4,
      (PEA)2PbCl4, (NMA)2PbCl4, and (PMA)2PbBr4 exhibit separate, broad "white"
      emission in the long wavelength range. Piezoelectric compounds identified from
      these 2D HOIPs may be considered for future piezoresponse-type energy or
      electronic applications.

PMID- 28749134
TI  - Carbon Textiles Modified with Copper-Based Reactive Adsorbents as Efficient Media
      for Detoxification of Chemical Warfare Agents.
AB  - Carbon textile swatch was oxidized and impregnated with copper hydroxynitrate. A
      subsample was then further heated at 280  degrees C to form copper oxide. The
      swatches preserved their integrity through the treatments. As final products,
      they exhibited remarkable detoxification properties for the nerve agent surrogate
      dimethyl chlorophosphate (DMCP). Based on the amount of reactive copper phases
      deposited on the fibers, their adsorption capacities were higher than those of
      the bulk powders. After 1 day exposure to DMCP (1:1 weight ratio adsorbent/DMCP),
      99% of the initial amount of DMCP was eliminated. A synergistic effect of the
      composite components was clearly seen. GC-MS results showed that the main surface
      reaction product was chloromethane. Its formation indicated hydrolysis as a
      detoxification path. Surface analyses showed phosphate bonding to the fibers and
      formation of copper chloride. The appearance of the latter species results in a
      clear textile color change, which suggests the application of these fabrics not
      only as catalytic protection agents but also as sensors of nerve agents.

PMID- 28749135
TI  - Spatially Selective, High-Density Placement of Polyfluorene-Sorted Semiconducting
      Carbon Nanotubes in Organic Solvents.
AB  - High-performance logic based on carbon nanotubes (CNTs) requires high-density
      arrays of selectively placed semiconducting CNTs. Although polymer-wrapping
      methods can allow CNTs to be sorted to a >99.9% semiconducting purity, patterning
      these polymer-wrapped CNTs is an outstanding problem. We report the directed self
      assembly of polymer-coated semiconducting CNTs using self-assembled monolayers
      that bind CNTs into arrays of patterned trenches. We demonstrate that CNTs can be
      placed into 100 nm wide HfO2 trenches with an electrical connection yield as high
      as 90% and into 50 nm wide trenches with a yield as high as 70%. Our directed
      self-assembly method is an important step forward in pitch scaling.

PMID- 28749136
TI  - High-Performance Pyrochlore-Type Yttrium Ruthenate Electrocatalyst for Oxygen
      Evolution Reaction in Acidic Media.
AB  - Development of acid-stable electrocatalysts with low overpotential for oxygen
      evolution reaction (OER) is a major challenge to produce hydrogen directly from
      water. We report in this paper a pyrochlore yttrium ruthenate (Y2Ru2O7-delta)
      electrocatalyst that has significantly enhanced performance toward OER in acid
      media over the best-known catalysts, with an onset overpotential of 190 mV and
      high stability in 0.1 M perchloric acid solution. X-ray absorption near-edge
      structure (XANES) indicates Y2Ru2O7-delta electrocatalyst had a low valence state
      that favors the high OER activity. Density functional theory (DFT) calculation
      shows this pyrochlore has lower band center energy for the overlap between Ru 4d
      and O 2p orbitals and is therefore more stable Ru-O bond than RuO2, highlighting
      the effect of yttrium on the enhancement in stability. The Y2Ru2O7-delta
      pyrochlore is also free of expensive iridium metal and thus is a cost-effective
      candidate for practical applications.

PMID- 28749137
TI  - Identification of Antiangiogenic Potential and Cellular Mechanisms of
      Napyradiomycin A1 Isolated from the Marine-Derived Streptomyces sp. YP127.
AB  - Angiogenesis is the process of new blood vessel formation. Excessive angiogenesis
      is a critical factor in the progression of cancer, macular degeneration, and
      other chronic inflammatory diseases. When investigating the effects of crude
      extracts of cultured marine microorganisms, an extract of the cultured
      Streptomyces sp. YP127 strain was found to inhibit human umbilical vein
      endothelial cell (HUVEC) tube formation. Bioassay-guided fractionation and
      spectroscopic data analyses led to the identification of napyradiomycin A1 (1) as
      an antiangiogenic component of the extract. Compound 1 inhibited HUVEC tube
      formation in a concentration-dependent manner. It inhibited endothelial cell
      proliferation but did not affect human dermal fibroblast proliferation. Compound
      1 also suppressed migration and invasion of vascular endothelial cells. In
      addition, compound 1 suppressed vascular endothelial cadherin expression and
      increased the permeability of the endothelial cell membrane. These results
      suggested that compound 1 modulates cell permeability and inhibits the
      angiogenesis of endothelial cells.

PMID- 28749138
TI  - Characterizing Drug-Target Residence Time with Metadynamics: How To Achieve
      Dissociation Rate Efficiently without Losing Accuracy against Time-Consuming
      Approaches.
AB  - Drug-target residence time plays a vital role in drug efficacy. However, there is
      still no effective strategy to predict drug residence time. Here, we propose to
      use the optimized (or minimized) structures derived from holo-state proteins to
      calculate drug residence time, which could give a comparable or even better
      prediction accuracy compared with those calculated utilizing a large number of
      molecular dynamics (MD) structures based on the Poisson process. Besides, in
      addition to the Poisson process, one may use fewer samples for predicting
      residence time due to the reason that, in a large extent, the calculated drug
      residence time is stable and independent of the number of samples used for the
      prediction. With remarkably reduced computational load, the proposed strategy may
      be promising for large-scale drug residence time prediction, such as post
      processing in virtual screening (VS) and lead compound optimization.

PMID- 28749139
TI  - Combined Molecular Dynamics Simulation-Molecular-Thermodynamic Theory Framework
      for Predicting Surface Tensions.
AB  - A molecular modeling approach is presented with a focus on quantitative
      predictions of the surface tension of aqueous surfactant solutions. The approach
      combines classical Molecular Dynamics (MD) simulations with a molecular
      thermodynamic theory (MTT) [ Y. J. Nikas, S. Puvvada, D. Blankschtein, Langmuir
      1992 , 8 , 2680 ]. The MD component is used to calculate thermodynamic and
      molecular parameters that are needed in the MTT model to determine the surface
      tension isotherm. The MD/MTT approach provides the important link between the
      surfactant bulk concentration, the experimental control parameter, and the
      surfactant surface concentration, the MD control parameter. We demonstrate the
      capability of the MD/MTT modeling approach on nonionic alkyl polyethylene glycol
      surfactants at the air-water interface and observe reasonable agreement of the
      predicted surface tensions and the experimental surface tension data over a wide
      range of surfactant concentrations below the critical micelle concentration. Our
      modeling approach can be extended to ionic surfactants and their mixtures with
      both ionic and nonionic surfactants at liquid-liquid interfaces.

PMID- 28749140
TI  - Geometry-Dependent Drying in Dead-End Nanochannels.
AB  - Liquid drying in nanoporous media is a key process in food, textile, oil and
      energy industries, but the corresponding kinetics remains poorly understood due
      to the structural complexity of nanoporous media. Here, we directly observe the
      drying process and study drying kinetics in single two-dimensional (2-D)
      nanochannels with height ranging from 29 to 122 nm. Two different drying
      behaviors are discovered in such nanoconfinements: continuous meniscus receding
      and discontinuous meniscus receding due to liquid bridge formation ahead of the
      meniscus, albeit similar drying rates. The geometry dependence of the measured
      drying rates is studied at different humidities and compared with a theoretical
      model considering liquid corner flow, liquid thin film flow, and vapor diffusion
      as contributors to the overall drying rates. Individual contributions from vapor
      and liquid transport inside the nanochannels to the drying kinetics are
      decoupled, and the water vapor diffusivity is successfully extracted. Our results
      show that both corner flow and vapor diffusion play important roles on water
      drying in nanochannels without sharp corners. Our findings further indicate that
      water vapor diffusion in nanoscale confinements can still be described by the
      classic Knudsen diffusion theory. These results provide new insights of liquid
      drying in nanoporous media and have implication in optimizing drying processes in
      industrial applications.

PMID- 28749141
TI  - Aggregation and Solvation of n-Butyllithium.
AB  - Solution characterizations and ligand binding constants were determined for n
      butyllithium in hydrocarbon and ethereal solvents using diffusion-ordered NMR. In
      hydrocarbon solvents, n-butyllithium exists primarily as an octamer at -40 
      degrees C and deaggregates to a hexamer when the temperature is increased. In the
      presence of THF or diethyl ether, n-butyllithium exists predominantly as a tetra
      solvated tetramer and deaggregates to a tetra-solvated dimer in the presence of a
      large excess or neat THF. The ligand binding constants for the tetra-solvated
      tetramers were measured using 1H NMR/DOSY titration.

PMID- 28749142
TI  - Chiral Macrocyclic Organocatalysts for Kinetic Resolution of Disubstituted
      Epoxides with Carbon Dioxide.
AB  - Among chiral macrocycles 1 synthesized, 1m with the 3,5
      bis(trifluoromethyl)phenylethynyl group was the best organocatalyst for the
      enantioselective synthesis of cyclic carbonates from disubstituted or
      monosubstituted epoxides and CO2. The X-ray crystal structure of 1m revealed a
      well-defined chiral cavity with multiple hydrogen-bonding sites that is suitable
      for the enantioselective activation of epoxides. A catalytic cycle proposed was
      supported by DFT calculations.

PMID- 28749143
TI  - Self-Assembly of Escin Molecules at the Air-Water Interface as Studied by
      Molecular Dynamics.
AB  - Escin belongs to a large class of natural biosurfactants, called saponins, that
      are present in more than 500 plant species. Saponins are applied in the
      pharmaceutical, cosmetics, and food and beverage industries due to their
      variously expressed bioactivity and surface activity. In particular, escin
      adsorption layers at the air-water interface exhibit an unusually high surface
      elastic modulus (>1100 mN/m) and a high surface viscosity (ca. 130 N.s/m). The
      molecular origin of these unusual surface rheological properties is still
      unclear. We performed classical atomistic dynamics simulations of adsorbed
      neutral and ionized escin molecules to clarify their orientation and interactions
      on the water surface. The orientation and position of the escin molecules with
      respect to the interface, the intermolecular interactions, and the kinetics of
      molecular aggregation into surface clusters are characterized in detail.
      Significant differences in the behavior of the neutral and the charged escin
      molecules are observed. The neutral escin rapidly assembles in a compact and
      stable surface cluster. This process is explained by the action of long-range
      attraction between the hydrophobic aglycones, combined with intermediate dipole
      dipole attraction and short-range hydrogen bonds between the sugar residues in
      escin molecules. The same interactions are expected to control the viscoelastic
      properties of escin adsorption layers.

PMID- 28749144
TI  - Isomer-Specific Hydrogen Bonding as a Design Principle for Bidirectionally
      Quantitative and Redshifted Hemithioindigo Photoswitches.
AB  - A new class of bidirectionally quantitative photoswitches based on the
      hemithioindigo (HTI) scaffold is reported. Incorporation of a pyrrole hydrogen
      bond donor leads to a bathochromic shift allowing for quantitative bidirectional
      isomerization. Additionally, extending conjugation from the electron-rich pyrrole
      results in quantitative visible-light photoswitches, as well as photoswitches
      that isomerize with red and near-infrared light. The presence of the hydrogen
      bond leading to the observed redshift is supported by computational and
      spectroscopic evidence.

PMID- 28749145
TI  - Molecular Interactions Control Quantum Chain Reactions toward Distinct
      Photoresponsive Properties of Molecular Crystals.
AB  - In this work, we fabricated four diphenylcyclopropenone (DPCP) crystals, which
      involved various molecular interactions encoded in individual molecular
      structures 1-4. On the basis of crystalline structural analysis and
      photoresponsive characterization of the resultant single-crystal microribbons 1
      4, we demonstrated that the magnitude of molecular interactions could effectively
      control the quantum chain reaction and the photoresponsive property of the DPCP
      crystals. The microribbons 1 and 2 having weak molecular interactions exhibited
      an efficient chain reaction and large mechanical photoresponses (i.e.,
      photomelting and photodeforming), whereas the microribbons 3 and 4 with strong
      molecular interactions exhibited no chain reaction and mechanical morphology
      change. Our work presented a new way to achieve molecular crystals with enhanced
      mechanical photoresponses.

PMID- 28749146
TI  - Rigid, Branched Porphyrin Antennas: Control over Cascades of Unidirectional
      Energy Funneling and Charge Transfer.
AB  - Porphyrin arrays consisting of three peripheral Zinc porphyrins (ZnPs) and a
      central free base porphyrin (H2P)-all rigidly linked to each other-serve as light
      harvesting antennas as well as electron donors and are flexibly coupled to an
      electron-accepting C60 to realize the unidirectional flow of (i) excited-state
      energy from the ZnPs at the periphery to the H2P, (ii) electrons to C60, and
      (iii) holes to H2P and, subsequently, to ZnP. Dynamics following photoexcitation
      are elucidated by time-resolved transient absorption measurements on the femto-,
      pico-, nano-, and microsecond time scales and are examined by multiwavelength as
      well as target analyses. Hereby, full control over the charge shift between H2P
      and ZnP to convert the (ZnP)3-H2P*+-C60*- charge-separated state into (ZnP)3*+
      H2P-C60*- charge-separated state is enabled by the solvent polarity: It is
      deactivated/switched-off in apolar toluene, while in polar benzonitrile it is
      activated/switched-on. Activating/switching impacts the recovery of the ground
      state via charge recombination rates, which differ by up to 2 orders of
      magnitude. All charge-separated states lead to the repopulation of the ground
      state with dynamics that are placed in the inverted region of the Marcus
      parabola.

PMID- 28749147
TI  - Redox Control over Acyl Hydrazone Photoswitches.
AB  - Photoisomerization provides a clean and efficient way of reversibly altering
      physical properties of chemical systems and injecting energy into them. These
      effects have been applied in development of systems such as photoresponsive
      materials, molecular motors, and photoactivated drugs. Typically, switching from
      more to less stable isomer(s) is performed by irradiation with UV or visible
      light, while the reverse process proceeds thermally or by irradiation using
      another wavelength. In this work we developed a method of rapid and tunable Z->E
      isomerization of C?N bond in acyl hydrazones, using aromatic thiols as
      nucleophilic catalysts. As thiols can be oxidized into catalytically inactive
      disulfides, the isomerization rates can be controlled via the oxidation state of
      the catalyst, which, together with the UV irradiation, provides orthogonal means
      to control the E/Z state of the system. As a proof of this concept, we have
      applied this method to control the diversity of acyl hydrazone based dynamic
      combinatorial libraries.

PMID- 28749148
TI  - Death narratives and cervical cancer: Impact of character death on narrative
      processing and HPV vaccination.
AB  - OBJECTIVES: Narratives hold promise as an effective public health message
      strategy for health behavior change, yet research on what types of narratives are
      most persuasive is still in the formative stage. Narrative persuasion research
      has identified 2 promising features of such messages that could influence
      behavior: whether characters live or die, and whether characters encounter key
      barriers. This study investigated the effects of these 2 narrative message
      features on young women's HPV vaccination intentions and examined mediating
      psychological processes of narrative persuasion in the context of cervical cancer
      messages. METHOD: We manipulated these 2 features in a narrative HPV vaccine
      intervention targeted to a national sample of U.S. women 18-26 who had not
      initiated the vaccine (N = 247). Participants were randomized in a 2 * 2 between
      subjects experiment. RESULTS: Compared to death narratives, survival narratives
      increased narrative believability and self-efficacy while lowering perceived
      barriers to vaccination. As features interacted, survival narratives featuring
      social barriers led to greater narrative transportation (absorption into the
      story) than other combinations. Moderated mediation analysis tested 10
      theoretically derived mediators; transportation and risk severity mediated the
      narrative-intention relationship. CONCLUSIONS: Findings provide evidence for key
      psychological postulates of narrative persuasion theory. Results inform practical
      application for the construction of effective narrative message content in
      cervical cancer prevention campaigns for young women. (PsycINFO Database Record

PMID- 28749149
TI  - Diversity shrinkage: Cross-validating pareto-optimal weights to enhance diversity
      via hiring practices.
AB  - To reduce adverse impact potential and improve diversity outcomes from personnel
      selection, one promising technique is De Corte, Lievens, and Sackett's (2007)
      Pareto-optimal weighting strategy. De Corte et al.'s strategy has been
      demonstrated on (a) a composite of cognitive and noncognitive (e.g., personality)
      tests (De Corte, Lievens, & Sackett, 2008) and (b) a composite of specific
      cognitive ability subtests (Wee, Newman, & Joseph, 2014). Both studies
      illustrated how Pareto-weighting (in contrast to unit weighting) could lead to
      substantial improvement in diversity outcomes (i.e., diversity improvement),
      sometimes more than doubling the number of job offers for minority applicants.
      The current work addresses a key limitation of the technique-the possibility of
      shrinkage, especially diversity shrinkage, in the Pareto-optimal solutions. Using
      Monte Carlo simulations, sample size and predictor combinations were varied and
      cross-validated Pareto-optimal solutions were obtained. Although diversity
      shrinkage was sizable for a composite of cognitive and noncognitive predictors
      when sample size was at or below 500, diversity shrinkage was typically
      negligible for a composite of specific cognitive subtest predictors when sample
      size was at least 100. Diversity shrinkage was larger when the Pareto-optimal
      solution suggested substantial diversity improvement. When sample size was at
      least 100, cross-validated Pareto-optimal weights typically outperformed unit
      weights-suggesting that diversity improvement is often possible, despite
      diversity shrinkage. Implications for Pareto-optimal weighting, adverse impact,
      sample size of validation studies, and optimizing the diversity-job performance
      tradeoff are discussed. (PsycINFO Database Record

PMID- 28749150
TI  - Positive and negative assessment center feedback in relation to development self
      efficacy, feedback seeking, and promotion.
AB  - In this field study we examined both positive and negative developmental feedback
      given in managerial assessment centers in relation to employees' self-efficacy
      for their ability to improve their relevant skills assessed in the centers, the
      extent to which they sought subsequent feedback from others at work, and the
      career outcome of being promoted to a higher level position within the
      organization. We found that feedback was related to self-efficacy for improvement
      which was in turn positively related to feedback seeking, which was positively
      linked to the career outcome of promotion (e.g., feedback leads to self-efficacy
      for improvement leads to feedback seeking leads to promotion). In addition, we
      tested boundary variables for the effects of feedback in this model. Both social
      support for development and implicit theory of ability moderated the effects of
      negative feedback on self-efficacy. Having more support and believing that
      abilities can be improved buffered the detrimental impact of negative feedback on
      self-efficacy. We discuss implications for theory, future research and practical
      implications drawing upon literature on assessment centers, feedback and feedback
      seeking, employee development and career success. (PsycINFO Database Record

PMID- 28749151
TI  - On the boundary conditions of effort losses and effort gains in action teams.
AB  - While people's willingness to work hard can be reduced in teams (i.e., effort
      losses in teams as compared with individual work), it is less recognized that
      teamwork can also stimulate additional efforts (i.e., effort gains). Building on
      and extending existing theory, we (a) suggest an integration of these two
      research streams, and (b) provide evidence for team-related effort gains in
      action teams. In a first study, we tested our predictions by reanalyzing a field
      data set of 302,576 swimming performances in individual and relay races (Neugart
      & Richiardi, 2013). Consistent with our hypotheses, we observed a linear increase
      in effort across the relay. The first relay swimmers showed effort losses in the
      relay as compared with the individual competition whereas the remaining relay
      swimmers showed effort gains. However, this was only evident (a) when team
      members could realistically expect meaningful team outcomes in return for their
      performance, and (b) when the valence of these outcomes was equivalent to
      individual competitions. If such favorable conditions were not given, we found
      effort losses in team as compared with individual competitions at all relay
      positions. Results of a second study (N = 228) showed that the linear increase in
      effort across the relay was indeed attributable to the team members' serial
      position and not to their relative strength. Together, the studies demonstrate
      the motivating potential of teamwork even in the high performance contexts of
      action teams, such as competitive sports relays, where athletes are already
      highly motivated in their individual competitions. (PsycINFO Database Record

PMID- 28749152
TI  - When fellow customers behave badly: Witness reactions to employee mistreatment by
      customers.
AB  - In 3 experiments, we examined how customers react after witnessing a fellow
      customer mistreat an employee. Drawing on the deontic model of justice, we argue
      that customer mistreatment of employees leads witnesses (i.e., other customers)
      to leave larger tips, engage in supportive employee-directed behaviors, and
      evaluate employees more positively (Studies 1 and 2). We also theorize that
      witnesses develop less positive treatment intentions and more negative
      retaliatory intentions toward perpetrators, with anger and empathy acting as
      parallel mediators of our perpetrator- and target-directed outcomes,
      respectively. In Study 1, we conducted a field experiment that examined real
      customers' target-directed reactions to witnessed mistreatment in the context of
      a fast-food restaurant. In Study 2, we replicated Study 1 findings in an online
      vignette experiment, and extended it by examining more severe mistreatment and
      perpetrator-directed responses. In Study 3, we demonstrated that employees who
      respond to mistreatment uncivilly are significantly less likely to receive the
      positive outcomes found in Studies 1 and 2 than those who respond neutrally. We
      discuss the implications of our findings for theory and practice. (PsycINFO
      Database Record

PMID- 28749153
TI  - Leadership training design, delivery, and implementation: A meta-analysis.
AB  - Recent estimates suggest that although a majority of funds in organizational
      training budgets tend to be allocated to leadership training (Ho, 2016;
      O'Leonard, 2014), only a small minority of organizations believe their leadership
      training programs are highly effective (Schwartz, Bersin, & Pelster, 2014),
      calling into question the effectiveness of current leadership development
      initiatives. To help address this issue, this meta-analysis estimates the extent
      to which leadership training is effective and identifies the conditions under
      which these programs are most effective. In doing so, we estimate the
      effectiveness of leadership training across four criteria (reactions, learning,
      transfer, and results; Kirkpatrick, 1959) using only employee data and we examine
      15 moderators of training design and delivery to determine which elements are
      associated with the most effective leadership training interventions. Data from
      335 independent samples suggest that leadership training is substantially more
      effective than previously thought, leading to improvements in reactions (delta =
      .63), learning (delta = .73), transfer (delta = .82), and results (delta = .72),
      the strength of these effects differs based on various design, delivery, and
      implementation characteristics. Moderator analyses support the use of needs
      analysis, feedback, multiple delivery methods (especially practice), spaced
      training sessions, a location that is on-site, and face-to-face delivery that is
      not self-administered. Results also suggest that the content of training,
      attendance policy, and duration influence the effectiveness of the training
      program. Practical implications for training development and theoretical
      implications for leadership and training literatures are discussed. (PsycINFO
      Database Record

PMID- 28749154
TI  - Rude color glasses: The contaminating effects of witnessed morning rudeness on
      perceptions and behaviors throughout the workday.
AB  - Using an experimental experience sampling design, we investigate how witnessing
      morning rudeness influences workers' subsequent perceptions and behaviors
      throughout the workday. We posit that a single exposure to rudeness in the
      morning can contaminate employees' perceptions of subsequent social interactions
      leading them to perceive greater workplace rudeness throughout their workday. We
      expect that these contaminated perceptions will have important ramifications for
      employees' work behaviors. In a 10-day study of 81 professional and managerial
      employees, we find that witnessed morning rudeness leads to greater perceptions
      of workplace rudeness throughout the workday and that those perceptions, in turn,
      predict lower task performance and goal progress and greater interaction
      avoidance and psychological withdrawal. We also find that the contaminating
      effect of morning rudeness depends on core self-evaluations (CSE)-employees high
      (vs. low) in CSE are affected less by exposure to morning rudeness. We discuss
      implications for practice and theory. (PsycINFO Database Record

PMID- 28749155
TI  - Assisting upon entry: Helping type and approach as moderators of how role
      conflict affects newcomer resource drain.
AB  - We extend recent research on the costs and benefits of helping to help providers
      by asking whether and under what conditions newcomer help giving may amplify or
      mitigate the role-conflict-based resource drain such individuals may experience
      in the context of their initial socialization. Drawing from conservation of
      resources (COR) theory, we propose that whether providing assistance to peers
      enhances or weakens newcomer help providers' resilience to such conflict-based
      resource drain (i.e., exhaustion) depends on both the type of help given
      (instrumental vs. emotional) and the orientation (more vs. less empowering) that
      newcomers adopt when providing it. We test our propositions on the basis of time
      lagged data collected from newly hired call center representatives at the end of
      their first and sixth months on the job. Results largely support our predictions,
      with instrumental assistance mitigating, and emotional assistance exacerbating,
      the role-conflict-based resource drain experienced by newcomer help providers.
      Moreover, these amplifying effects of emotional help provision on the conflict
      exhaustion relationship are largely eliminated among those newcomer help
      providers reporting a more empowering approach to help provision. (PsycINFO
      Database Record

PMID- 28749156
TI  - Employee conscientiousness, agreeableness, and supervisor justice rule
      compliance: A three-study investigation.
AB  - Researchers have paid limited attention to what makes organizational authority
      figures decide to treat their employees either justly or unjustly. Drawing from
      the actor-focused model of justice, as well as the stereotype content model, we
      argue that employee conscientiousness and agreeableness can impact the extent to
      which supervisors adhere to normative rules for distributive, procedural,
      informational, and interpersonal justice, as a result of supervisors' evaluations
      of their employees' effort and their liking of the employees. Supervisory
      compliance with justice rules may, in turn, impact the extent to which employees
      judge themselves to be treated either justly or unjustly. We tested these
      possibilities in 3 studies. In Study 1, we utilized a meta-analysis to
      demonstrate positive relationships between employees' conscientiousness,
      agreeableness, and their justice perceptions. In Study 2, we conducted 3
      experiments to test the causal relationship between employee personality and
      supervisor intentions to comply with justice rules. In Study 3, we conducted an
      employee-supervisor dyadic field survey to examine the entire mediation model.
      Results are discussed in terms of the potential roles that both employees and
      supervisors may play in shaping employees' justice perceptions. (PsycINFO
      Database Record

PMID- 28749157
TI  - Disentangling the relationship between gender and work-family conflict: An
      integration of theoretical perspectives using meta-analytic methods.
AB  - Implicit in many discussions of work-family issues is the idea that managing the
      work-family interface is more challenging for women than men. We address whether
      this intuition is supported by the empirical data via a meta-analysis of gender
      differences in work-family conflict (WFC) based on more than 350 independent
      samples (N > 250,000 workers). Challenging lay perceptions, our results
      demonstrate that men and women generally do not differ on their reports of WFC,
      though there were some modest moderating effects of dual-earner status, parental
      status, type of WFC (i.e., time-, strain-, vs. behavior-based), and when limiting
      samples to men and women who held the same job. To better understand the
      relationship between gender and WFC, we engaged in theory-testing of mediating
      mechanisms based on commonly invoked theoretical perspectives. We found evidence
      in support of the rational view, no support for the sensitization and male
      segmentation perspectives, and partial support for the asymmetrical domain
      permeability model. Finally, we build theory by seeking to identify omitted
      mediators that explain the relationship between gender and work-interference-with
      family, given evidence that existing theoretically specified mechanisms are
      insufficient to explain this relationship. Overall, we find more evidence for
      similarity rather than difference in the degree of WFC experienced by men and
      women. (PsycINFO Database Record

PMID- 28749158
TI  - A wait-list controlled study of a trauma-focused cognitive behavioral treatment
      for intermittent explosive disorder in Timor-Leste.
AB  - We tested a trauma-focused, cognitive-behavior therapy treatment (TF-CBT-anger)
      for intermittent explosive disorder (IED) and related dimensions of anger adapted
      to the local culture in postconflict Timor-Leste. The intention-to-treat sample
      (n = 78) comprised Timorese nationals (women = 49; men = 29), ages 18 years and
      older, meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.)
      criteria for IED, with equal numbers (n = 39 each) being randomized to the
      treatment group (TG) and wait-list (WL). Assessments were made at 1 week prior to
      therapy, immediately at posttreatment, and at 1 month follow-up. Primary measures
      included an IED diagnosis made according to the East Timor explosive anger
      measure and the directionality of expression and control of anger assessed by 4
      dimensions of the State-Trait Anger Expression Inventory (STAXI-2). Secondary
      measures included psychological distress assessed using the Kessler scale and an
      index of posttraumatic stress disorder (PTSD) assessed using the Harvard Trauma
      Questionnaire. In the TG, there was a decline in IED from 100% to zero at follow
      up. In the WL, more than 70% (of the 100% at baseline) showed persisting IED at
      second and third assessments. The TG alone showed significant (p < .05)
      improvements on all STAXI-2 scales, the effect sizes for the intervention being
      uniformly large (>0.80). Psychological distress and PTSD showed substantial
      reductions in the TG but not the WL group. Although based on a modest-sized
      sample, our findings provide the first evidence in support of the efficacy of TF
      CBT-anger for IED in a culturally diverse, postconflict setting. (PsycINFO
      Database Record

PMID- 28749159
TI  - Hierarchical exploratory factor analyses of the Woodcock-Johnson IV Full Test
      Battery: Implications for CHC application in school psychology.
AB  - The Woodcock-Johnson (fourth edition; WJ IV; Schrank, McGrew, & Mather, 2014a)
      was recently redeveloped and retains its linkage to Cattell-Horn-Carroll theory
      (CHC). Independent reviews (e.g., Canivez, 2017) and investigations (Dombrowski,
      McGill, & Canivez, 2017) of the structure of the WJ IV full test battery and WJ
      IV Cognitive have suggested the need for additional factor analytic exploration.
      Accordingly, the present study used principal axis factoring (PAF) followed by
      the Schmid and Leiman (SL; Schmid & Leiman, 1957) procedure with the 2 school
      aged correlation matrices from the normative sample to determine the degree to
      which the WJ IV total battery structure could be replicated. Although 7 factors
      emerged across the 9 to 19 age range, the pattern of subtests loadings did not
      fully cohere with the structure presented in the Technical Manual, most notably
      for the academic fluency subtests. Also, the Fluid Reasoning (Gf) and
      Quantitative Reasoning (Gq) subtests coalesced to form a combined factor rather
      than 2 separate factors and the Long Term Retrieval (Gltr) subtests aligned with
      a variety of different factors. The results of this study indicated that the
      general intelligence factor variance far exceeded the variance attributed to the
      lower-order CHC factors. The combination of subtest migration and nominal
      total/common variance of the CHC lower-order factors suggests caution when
      interpreting the myriad CHC-related indices when making high stakes decisions.
      Implications for clinical practice are discussed. (PsycINFO Database Record

PMID- 28749160
TI  - The unfolding impact of leader identity entrepreneurship on burnout, work
      engagement, and turnover intentions.
AB  - The present research expands upon previous theory and empirical work concerning
      the leadership-health link by examining the lagged effects of leader identity
      entrepreneurship (i.e., leaders' creation of a sense of "we" and "us" among team
      members) on team members' burnout, work engagement and turnover intentions. We
      report results from a 2-wave field study with employees from a large solar panel
      producing organization in China conducted over a 10-month period. Findings
      indicate that perceived leader identity entrepreneurship predicted greater
      subsequent work engagement among team members, as well as lower subsequent
      burnout and turnover intentions. Moreover, effects on reduced turnover intentions
      were mediated by reduced burnout and increased work engagement. These findings
      are the first to examine how leader identity entrepreneurship impacts subsequent
      employee health and turnover intentions and suggest that leaders help to promote
      health and well-being in the workplace by creating and developing a sense of
      shared identity among those they lead. (PsycINFO Database Record

PMID- 28749161
TI  - Self-employment, personal values, and varieties of happiness-unhappiness.
AB  - This study compares personal values and forms of happiness between self-employed
      workers and those employed in an organization. Values are examined through
      Schwartz's (1999) established model, and happiness is measured in terms of
      personal flourishing and both job-specific and general hedonic well-being. In two
      nationally representative samples, self-employed workers are found to value self
      direction and stimulation in their lives to a significantly greater degree than
      do organizational employees, but not to differ in other types of value. Well
      being differences are predicted to depend on whether or not workers supervise
      others, such that any well-being advantages of self-employment are expected to
      occur only for self-employed workers without subordinates. As predicted, job
      satisfaction in self-employment is found to exceed that of organizational workers
      primarily for those who do not supervise others. In respect of personal
      flourishing, self-employed workers report significantly greater accomplishment in
      their lives, and that difference is again found only for workers without
      supervisory responsibility. However, strain experienced in a job and context-free
      hedonic well-being are found to be similar between self- and organizational
      employment. Refinements are proposed to research methods and practical
      procedures. (PsycINFO Database Record

PMID- 28749162
TI  - A workplace incivility roadmap: Identifying theoretical speedbumps and
      alternative routes for future research.
AB  - Andersson and Pearson's (1999) seminal article on workplace incivility has paved
      the way for nearly two decades of research focusing on rude and discourteous
      behavior at work. We now have a better understanding of the dynamics associated
      with uncivil workplace interactions including the characteristics of those who
      instigate and are targeted with workplace incivility, the negative consequences
      of incivility, the mechanisms that link incivility and negative outcomes, and the
      boundary conditions that affect these relationships. The present article provides
      a "roadmap" for workplace incivility researchers by identifying five assumptions
      that we propose are acting as "speedbumps" in current workplace incivility
      research by limiting advancements about what workplace incivility is and how it
      functions. We then introduce five "alternative routes" for future workplace
      incivility research based on these identifications. Our goal is to guide and
      accelerate research toward a more nuanced understanding of workplace incivility
      as behavior that occurs within an organizational system. (PsycINFO Database
      Record

PMID- 28749163
TI  - Development of a paediatric head voxel model database for dosimetric
      applications.
AB  - OBJECTIVE: To develop a database of paediatric head voxel models intended for
      Monte Carlo (MC) dosimetric applications. METHODS: Seventeen head and neck CT
      image data sets were retrieved from the picture archiving and communicating
      system of our hospital and were reformed into voxel models. 22 organs were
      segmented at each data set. The segmented organ masses were compared to the
      respective age- and gender-specific ICRP reference mass value. Adjustments were
      made such that segmented and reference mass values coincide within a tolerance of
      10%. A dental cone beam CT cleft palate simulation study was set up to
      demonstrate the applicability of our database to MC frameworks and to investigate
      the need for age- and gender-specific paediatric models. RESULTS: The designed
      database covers the age range from 2 months to 14 years old. Each model
      represents a reference head voxel phantom for its corresponding age and gender
      category. The simulation study revealed absorbed organ dose differences larger
      than 50% among the 5, 8 and 12 years old models when exposed to identical
      conditions. CONCLUSION: Children cannot be represented by one average phantom
      covering the entire age range like adults due to the fact that their organs
      change rapidly in size and shape. A database of paediatric head voxel models was
      designed to enable dose calculations via MC simulations. Advances in knowledge:
      The application of each model of the database to MC frameworks provides age- and
      gender-specific organ dose estimations from medical exposures in the head and
      neck region.

PMID- 28749164
TI  - Distribution and chemical forms of gadolinium in the brain: a review.
AB  - In the 3 years since residual gadolinium-based contrast agent (GBCA) in the brain
      was first reported, much has been learned about its accumulation, including the
      pathway of GBCA entry into the brain, the brain distribution of GBCA and its
      excretion. Here we review recent progress in understanding the routes of
      gadolinium deposition in brain structures.

PMID- 28749165
TI  - Impact of robotic ultrasound image guidance on plan quality in SBRT of the
      prostate.
AB  - OBJECTIVE: Ultrasound provides good image quality, fast volumetric imaging and is
      established for abdominal image guidance. Robotic transducer placement may
      facilitate intrafractional motion compensation in radiation therapy. We consider
      integration with the CyberKnife and study whether the kinematic redundancy of a
      seven-degrees-of-freedom robot allows for acceptable plan quality for prostate
      treatments. METHODS: Reference treatment plans were generated for 10 prostate
      cancer cases previously treated with the CyberKnife. Considering transducer and
      prostate motion by different safety margins, 10 different robot poses, and 3
      different elbow configurations, we removed all beams colliding with robot or
      transducer. For each combination, plans were generated using the same strict dose
      constraints and the objective to maximize the target coverage. Additionally,
      plans for the union of all unblocked beams were generated. RESULTS: In 9 cases
      the planning target coverage with the ultrasound robot was within 1.1 percentage
      points of the reference coverage. It was 1.7 percentage points for one large
      prostate. For one preferable robot position, kinematic redundancy decreased the
      average number of blocked beam directions from 23.1 to 14.5. CONCLUSION: The
      impact of beam blocking can largely be offset by treatment planning and using a
      kinematically redundant robot. Plan quality can be maintained by carefully
      choosing the ultrasound robot position and pose. For smaller planning target
      volumes the difference in coverage is negligible for safety margins of up to 35
      mm. Advances in knowledge: Integrating a robot for online intrafractional image
      guidance based on ultrasound can be realized while maintaining acceptable plan
      quality for prostate cancer treatments with the CyberKnife.

PMID- 28749166
TI  - Ablative safety margin depicted by fusion imaging with post-treatment contrast
      enhanced ultrasound and pre-treatment CECT/CEMRI after radiofrequency ablation
      for liver cancers.
AB  - OBJECTIVE: To evaluate the value of fusion imaging with post-treatment contrast
      enhanced ultrasound (CEUS) and pre-treatment contrast-enhanced CT/MRI
      (CECT/CEMRI) in evaluating ablative safety margin after percutaneous ultrasound
      (US)-guided radiofrequency ablation (RFA) for liver cancers. METHODS: 34
      consecutive patients with 47 liver lesions who had undergone RFA were included.
      Fusion imaging with post-treatment CEUS and pre-treatment CECT/CEMRI was carried
      out to evaluate local treatment response and ablative safety margin within 1-3
      days after RFA. The minimal ablative safety margins of the ablation zones were
      recorded. The complete response (CR) rate was calculated with reference to
      CECT/CEMRI results 1 month after RFA. The local tumour progression (LTP) was also
      recorded. RESULTS: Of the 47 ablation zones, 47 (100%) were clearly depicted with
      CEUS-CECT/CEMRI fusion imaging, 36 (76.6%) with US-CECT/CEMRI fusion imaging and
      21 (44.7%) with conventional US (both p < 0.001). The minimal ablative safety
      margins were great than or equal to 5 mm in 28 ablation zones, between 0 and 5 mm
      in 15, and less than 0 mm in 4. For the four lesions without enough ablative
      safety margin, three were referred to follow-up because CEUS showed larger
      ablation zones than pre-treatment lesions and the remaining lesion was subject to
      additional RFA 5 days after the first RFA. The CR rate was 95.7% (45/47) with
      reference to CECT/CEMRI results 1 month after RFA. During 2 to 34 months follow
      up, LTP was found in two (4.4%) of 45 lesions with CR. Insufficient ablative
      safety margin was more commonly found in those lesions with LTP than those
      without LTP (1/4 vs 1/43, p < 0.001). CONCLUSION: Fusion imaging with post
      treatment CEUS and pre-treatment CECT/CEMRI can depict the ablative safety margin
      accurately after RFA. Inadequate ablative safety margin is associated with LTP.
      Depiction of ablative safety margin by fusion imaging after ablation might be
      considered as a routine procedure to assess the treatment response of RFA.
      Advances in knowledge: Fusion imaging with post-treatment CEUS and pre-treatment
      CECT/CEMRI is an effective method to evaluate the ablative safety margin early
      after RFA. Therefore, it should be recommended to be used as a routine procedure
      after RFA for liver cancers.

PMID- 28749167
TI  - Diagnostic value of semi-quantitative and quantitative analysis of functional
      parameters in multiparametric MRI of the prostate.
AB  - OBJECTIVE: To determine the diagnostic value of semi-quantitative and
      quantitative parameters of three functional techniques in multiparametric (mp)
      MRI of the prostate. METHODS: Mp-MRI was performed in 110 patients with suspicion
      of prostate cancer (PCA) before transrectal ultrasound (TRUS)-guided core biopsy.
      Peak-enhancement, initial and post-initial enhancement, initial area under
      gadolinium curve, Ktrans (forward rate constant), Kep (efflux rate constant), Ve
      (extracellular volume), ADC (apparent diffusion coefficient) and MR spectroscopy
      ratio were obtained for malignant and benign lesions. For iAUGC, Ktrans, Kep and
      Ve we evaluated median, mean and the difference (Diff) between mean and median.
      For ADC we evaluated mean, median, Diff between mean and median, and min. In
      addition, we evaluated these parameters in dependence of Gleason score in PCA.
      Receiver operating characteristic analysis and area under curve (AUC) were
      determined. RESULTS: ADC min and Kep Diff were the best predictors of malignancy
      in all lesions (AUC: 0.765). ADC min was the best predictor of malignancy for
      lesions in peripheral zone (PZ) (AUC: 0.7506) and Kep Diff was the best predictor
      of malignancy for lesions in transitional zone (AUC: 0.7514). Peak enhancement
      was the best parameter in differentiation of low-grade PCA with Gleason score 6
      from high-grade PCA with Gleason score >= 7 (AUC: 0.7692). CONCLUSION: ADC min
      can differentiate PCA from benign prostate lesions in PZ. Kep Diff could possibly
      improve prostate cancer detection in. Peak enhancement might be able to
      differentiate low grade from high-grade PCA. Semi-quantitative and quantitative
      parameters may be useful for the functional techniques in mp-MRI. Advances in
      knowledge: ADC min can differentiate PCA from benign prostate lesions in PZ. Peak
      enhancement might be able to differentiate low grade from high-grade PCA.

PMID- 28749168
TI  - Anxiety reduction and emotional self-care using the U-technique in radiology
      departments.
AB  - Daily clinical practice is an important source of stress and emotional
      exhaustion. In the health field, patients could experience a significant number
      of emotional reactions. There are high levels of anxiety in patients referred for
      medical imaging, and these levels are even higher in patients undergoing
      complicated diagnostic procedures. All this shows the need to understand that
      anxiety must be diagnosed and treated. This situation forces radiologist to
      develop emotional and social skills to resolve difficulties that may arise in the
      communicative act. In the patient-radiologist interaction, many elements have
      been analysed, being communication and communicative skills one of the most
      important elements. The objective is to present an emotional management tool, the
      U-technique. It consists of four movements: sympathize, empathize, feel the
      antidote emotion and spread the antidote emotion in order that the health
      professionals recognize their emotional state in each moment of the relationship
      with the patient.

PMID- 28749169
TI  - Effects of Sodium Glucose Cotransporter-2 Inhibitors on Serum Uric Acid in Type 2
      Diabetes Mellitus.
AB  - Hyperuricemia has been linked to metabolic syndrome, cardiovascular disease, and
      chronic kidney disease. Hyperuricemia and type 2 diabetes mellitus were inter
      related, type 2 diabetes mellitus was more at risk of having a higher serum uric
      acid level, and also individuals with higher serum uric acid had higher risk of
      developing type 2 diabetes in the future. Insulin resistance seems to play an
      important role in the causal relationship between metabolic syndrome, type 2
      diabetes, and hyperuricemia. Oral diabetic drugs that would have additional
      beneficial effects on reducing serum uric acid levels are of importance.
      Selective SGLT2 inhibitors were extensively studied in type 2 diabetes mellitus
      and were found to have improvement of glycemic control, in addition to their
      proven metabolic effects on weight and blood pressure. Additional beneficial
      effect of SGLT2 inhibitors on serum uric acid level reduction is investigated.
      Recently, data have been accumulating showing that they have additional
      beneficial effects on serum uric acid reduction. As for the postulated mechanism,
      serum uric acid decreased in SGLT2 inhibitor users as a result of the increase in
      the urinary excretion rate of uric acid, due to the inhibition of uric acid
      reabsorption mediated by the effect of the drug on the GLUT9 isoform 2, located
      at the collecting duct of the renal tubule.

PMID- 28749170
TI  - Multidetector CT in detection of troublesome posterior sectoral hepatic duct
      communicating with cystic duct.
AB  - OBJECTIVE: To investigate whether multiple detector CT (MDCT) could detect
      troublesome aberrant posterior sectoral hepatic duct (PHD) communicating with
      cystic duct (CD). METHODS: The most troublesome bile duct anomaly during
      cholecystectomy is an aberrant PHD communicating with CD. It has been suggested
      that an unenhanced small duct between Rouviere's sulcus and CD on MDCT could be
      coincident to an aberrant PHD communicating with CD. A total of 224 patients who
      underwent laparotomy with complete lymph node dissection in the hepatoduodenal
      ligament for hepatobiliary or pancreatic tumour were enrolled. Retrospective
      review of preoperative MDCT images and surgical records was performed. RESULTS:
      Preoperative MDCT detected 8 (3.6%) unenhanced ducts between Rouviere's sulcus
      and CD. Surgical records identified 7 (3.1%) cases of aberrant PHD communicating
      with CD, and all 7 cases showed an unenhanced duct between Rouviere's sulcus and
      CD on preoperative MDCT imaging. Among the 7 patients, 5 (71%) were without bile
      duct dilatation. CONCLUSION: MDCT could detect troublesome aberrant PHD
      communicating with CD, regardless of the presence or absence of bile duct
      dilatation. Advances in knowledge: MDCT could detect most troublesome PHD
      communicating with CD, regardless of the presence or absence of bile duct
      dilatation.

PMID- 28749171
TI  - Prospective evaluation of a specific technique of sexual function preservation in
      external beam radiotherapy for prostate cancer.
AB  - OBJECTIVE: Sexual preservation is an important issue in the treatment of
      localized prostate cancer. A technique of irradiation was developed to better
      preserve this function and has been evaluated. METHODS: Eleven patients, with no
      erectile dysfunction (ED), were treated with daily IMRT-IGRT (total dose: 76-78
      Gy). The pudendal arteries, penile bulb and cavernous body were delineated on the
      planning CT scan. The doses to these structures (with a 5 mm margin) were
      optimized to be as low as possible. The erectile function was documented using
      IIEF-5 scores at baseline, 6 months, 1 and 2 years. No ED was defined by an IIEF5
      >= 20/25, a mild ED by an IIEF5 score of 17-19 and an important ED by a score
      <17. RESULTS: The mean age was 68.4 years. At the median follow-up of 36 months,
      there was no biochemical relapse. Before RT, the mean IIEF5 score in all 11
      patients was 23.4 (range, 20-25). At 6, 12, 18 and 24 months after RT, the mean
      IIEF scores were 21.2 (14-25), 21.3 (14-25), 21.8 (16-25) and 21.8 (16-25),
      respectively. At 2 years, 8 patients (72.7%) had no ED and 2 patients (18.2%)
      experienced a mild ED. The only patient with an important ED had a medical
      treatment and recovered a satisfactory IIEF score from 16 to 24. CONCLUSION: The
      results of this technique of optimisation for sexual preservation are
      encouraging. Despite a mean age close to 70 years at the time of treatment, 90.9%
      of the patients had no to mild ED at 2 years. This rate increases at 100% with
      medical treatment. Advances in knowledge: Dose optimization on sexual organs is
      possible and could decrease the ED rates.

PMID- 28749172
TI  - No differences in radiological changes after 3D conformal vs VMAT-based
      stereotactic radiotherapy for early stage non-small cell lung cancer.
AB  - OBJECTIVE: To compare patterns of acute and late radiological lung injury
      following either 3D conformal or image-guided volumetric modulated arc therapy
      stereotactic radiotherapy for Stage I non-small-cell lung cancer. METHODS: We
      included 148 patients from a prospective mono-institutional stereotactic body
      radiation therapy (SBRT) series (time interval 2004-2014), treated with
      prescription BED10 Gy (at 80%) in the range 100-120 Gy. The first 95 patients
      (2004-2010) were planned with 3D-CRT, with a stereotactic body frame. The second
      cohort (2010-2014) included 53 patients, planned with volumetric IMRT on a
      smaller planning target volume generated from a patient's specific internal
      target volume, with a frameless approach through cone-beam CT guidance. Acute and
      late radiological modifications were scored based on modified Kimura's and
      Koenig's classifications, respectively. RESULTS: Median follow-up time was 20.5
      months. The incidence of acute radiological changes was superimposable between
      the groups: increased density was observed in 68.4 and 64.2% of patients for 3D
      CRT and VMAT, respectively, and patchy ground glass opacity in 23.7 and 24.5%,
      respectively; diffuse ground glass opacity was 2.6 vs 9.4%, respectively, and
      patchy consolidation 2.6 vs 1.9%, respectively. Late changes occurred in
      approximately 60% of patients: modified conventional pattern was the most
      frequent modification (25 vs 32.6%, respectively); other patterns were less
      common (mass-like 19.6 vs 17.4%, and scar-like 13 vs 10.9%, respectively).
      CONCLUSION: Results of the present study indicate that the pattern of
      radiological lung changes following SBRT for peripheral early stage non-small
      cell lung cancer is not influenced by the different techniques used for planning
      and delivery. Advances in knowledge: This comparative observational study shows
      that smaller margins, image guidance and most importantly dose distribution do
      not change the pattern of radiological injury after lung SBRT; the same scoring
      system can be used, and expected incidence is similar.

PMID- 28749173
TI  - MRI assessment of sacroiliitis for the diagnosis of axial spondyloarthropathy:
      comparison of fat-saturated T2, STIR and contrast-enhanced sequences.
AB  - OBJECTIVE: To evaluate whether there are significant differences between contrast
      enhanced fat-saturated T1 weighted imaging and non-enhanced fat-suppression
      imaging for diagnosing sacroiliitis in patients with inflammatory back pain.
      METHODS: 92 patients, consisting of 46 males and 46 females (mean age: 34 years;
      range: 15-63 years), who met at least 4 out of 5 Assessment in SpondyloArthritis
      international Society criteria for inflammatory low back pain were enrolled in
      this study. All patients underwent MRI consisting of a coronal short tau
      inversion recovery (STIR) sequence, axial fat-saturated T2 weighted imaging
      (T2FS), and coronal and axial contrast-enhanced fat-saturated T1 weighted imaging
      (c & a T1CE). Two observers independently reviewed an image set of coronal STIR
      with axial T2FS, and an image set of c & a T1CE, at separate times. The degree of
      bone marrow edema and osteitis was evaluated from each image set. A decision for
      sacroiliitis positivity for each image set was made based on the findings. The
      presence of additional active inflammatory findings of spondyloarthropathy such
      as synovitis, enthesitis and capsulitis were also evaluated. RESULTS:
      Interobserver and intersequence agreement for the degree of bone marrow edema and
      osteitis were good or excellent in all quadrants. Cohen's kappa coefficients for
      sacroiliitis positivity between the two observers were 0.978 and 0.956, and
      Cohen's kappa coefficients between the two image sets for each observer were
      0.892 and 0.870, respectively. The intersequence agreement of additional active
      inflammatory findings was substantial, and the interobserver agreement was almost
      perfect or substantial. CONCLUSION: STIR with T2FS image is comparable to T1CE
      image for diagnosing spondyloarthropathy. T1CE images may have a role in
      evaluating additional active inflammatory findings of spondyloarthropathy such as
      synovitis, enthesitis and capsulitis. Advances in knowledge: Coronal STIR with
      axial T2FS may be sufficient for diagnosis spondyloarthropathy without use of
      contrast administration.

PMID- 28749174
TI  - Microbeam radiation therapy - grid therapy and beyond: a clinical perspective.
AB  - Microbeam irradiation is spatially fractionated radiation on a micrometer scale.
      Microbeam irradiation with therapeutic intent has become known as microbeam
      radiation therapy (MRT). The basic concept of MRT was developed in the 1980s, but
      it has not yet been tested in any human clinical trial, even though there is now
      a large number of animal studies demonstrating its marked therapeutic potential
      with an exceptional normal tissue sparing effect. Furthermore, MRT is
      conceptually similar to macroscopic grid based radiation therapy which has been
      used in clinical practice for decades. In this review, the potential clinical
      applications of MRT are analysed for both malignant and non-malignant diseases.

PMID- 28749175
TI  - Direct shoulder magnetic resonance arthrography for superior labral anterior-to
      posterior (SLAP) and Bankart lesions: investigation into the appropriate dose and
      level of local anesthesia.
AB  - OBJECTIVE: To compare contrast leakage, pain score, image quality and diagnostic
      performance at different doses and levels of local anaesthesia for direct
      shoulder magnetic resonance arthrography. METHODS: Patients (n = 157) were
      prospectively enrolled and allocated to Group 1 (no local anaesthetic), Group 2
      (local anaesthesia to subcutaneous fat level; lidocaine 1-2 ml), Group 3 (to
      deltoid muscle level; 3-5 ml), or Group 4 (to subscapularis muscle level; 6-8
      ml). We evaluated the frequency of contrast leakage,
      periprocedural/postprocedural pain, contrast-to-noise ratio of the intra
      articular signal, and subjective image noise/image sharpness. Radiological
      diagnoses of superior anterior-to-posterior (SLAP) and Bankart lesions were
      assessed. All data were analysed by one-way analysis of variance/Kruskal-Wall,
      Chi2/Fisher's exact and DeLong's tests. RESULTS: The frequency of contrast
      leakage from the injection path and subjective image noise were significantly
      lower in Groups 1 and 2 than in Groups 3 and 4 (p = 0.001-0.04).
      Periprocedural/postprocedural pain scores among Groups 2-4 were similar and lower
      than those of Group 1. The contrast-to-noise ratio (p = 0.11-0.97) and image
      sharpness (p = 0.12-0.43) were similar among Groups 2-4 and significantly lower
      than those of Group 1 (p = 0.001-0.02). The diagnostic performance for the
      assessment of superior anterior-to-posterior and Bankart lesions was better in
      Groups 2-4 than in Group 1, although there were no significant differences (p =
      0.23-0.99). CONCLUSION: Local anaesthesia with 1-2 ml lidocaine at subcutaneous
      fat level reduced pain and provided optimal image quality in direct shoulder
      magnetic resonance arthrography. Advances in knowledge: This method can increase
      image quality, reduce periprocedural/postprocedural pain and potentially reduce
      the need for re-examination.

PMID- 28749176
TI  - Quantifying potential reduction in contrast dose with monoenergetic images
      synthesized from dual-layer detector spectral CT.
AB  - OBJECTIVE: To estimate the potential dose reduction in iodinated contrast when
      interpreting monoenergetic images from spectral CT. METHODS: 51 paediatric
      patients received contrast-enhanced CT simulation for radiation therapy using a
      single-source, dual-layer detector spectral CT. The contrast-to-noise ratios
      (CNRs) of blood vessels were measured relative to surrounding soft tissue. CNRs
      on monoenergetic 40-70 keV images were compared with polychromatic 120 kVp
      images. To compare with in vivo results, a phantom with iodine inserts (2-20 mg
      ml-1 concentration) was scanned and CNRs were calculated relative to water
      background. RESULTS: Monoenergetic keV and body site had significant effects on
      CNR ratio (p < 0.0001). Across all body sites, the mean CNR ratio
      (monoenergetic/polychromatic CNR) was 3.3 (20th percentile [%20] 2.6), 2.4 (%20
      2.1), 1.7 (%20 1.5), 1.2 (%20 1.0) for 40, 50, 60 and 70 keV images,
      respectively. Image noise was highest at 40 keV and lowest at 70 keV. Phantom
      measurements indicated that the same CNR as 120 kVp images can be achieved with a
      4.0-fold lower iodine concentration on 40 keV images and 2.5-fold lower on 50 keV
      images. CONCLUSION: 50 keV monoenergetic images provided the best balance of
      improved CNR on all studies (mean 2.4-fold increase in vivo) for enhancing
      vessels vs image noise. A 50% reduction in contrast dose on a 50 keV image should
      maintain comparable or better CNR as compared with polychromatic CT in over 80%
      of CT studies. Advances in knowledge: Use of a novel, single-source, dual-layer
      detector spectral CT scanner to improve visualization of contrast-enhanced blood
      vessels will reduce the amount of iodinated contrast required for radiation
      oncology treatment planning.

PMID- 28749177
TI  - SPRINT trial: It's not just the blood pressure!
AB  - Background The SPRINT trial showed a beneficial effect of systolic blood pressure
      treatment targets of 120 mmHg on cardiovascular risk compared to targets of 140
      mmHg. However, differences in medication use, most importantly diuretics, are
      suggested as an alternative explanation. This post-hoc analysis aimed to
      determine whether the reduced event rate can be attributed to changes in systolic
      blood pressure (DeltaSBP) . Methods Analyses were based on all 9361 participants
      of the SPRINT trial. DeltaSBP was defined as the change between baseline and 6
      month follow-up systolic blood pressure. Major cardiovascular events were
      myocardial infarction, other acute coronary syndromes, stroke, heart failure, or
      cardiovascular death. Cox regression was used to describe the relation between
      DeltaSBP and major cardiovascular events. Analyses were performed separately for
      patients in the lowest tertile of baseline systolic blood pressure, as the SPRINT
      trial reported the highest treatment effect in this subgroup. Results The
      relation between DeltaSBP and major cardiovascular events was a hazard ratio per
      10 mmHg decrease of 0.93 (95% confidence interval 0.89-0.98). Similar results
      were found within the lowest tertile of baseline systolic blood pressure: hazard
      ratio per 10 mmHg decrease 0.91 (95% confidence interval 0.82-1.01). Conclusion
      Our results show that lowering blood pressure prevents cardiovascular disease.
      However, not all the positive effects in the SPRINT trial could be explained by
      DeltaSBP. Alternative explanations, such as differences in medication use, should
      be considered for the positive findings of the SPRINT trial.

PMID- 28749178
TI  - Validation and recalibration of the Framingham cardiovascular disease risk models
      in an Australian Indigenous cohort.
AB  - Background In Australia, clinical guidelines for primary prevention of
      cardiovascular disease recommend the use of the Framingham model to help identify
      those at high risk of developing the disease. However, this model has not been
      validated for the Indigenous population. Design Cohort study. Methods Framingham
      models were applied to the Well Person's Health Check (WPHC) cohort (followed
      1998-2014), which included 1448 Aboriginal and Torres Strait Islanders from
      remote Indigenous communities in Far North Queensland. Cardiovascular disease
      risk predicted by the original and recalibrated Framingham models were compared
      with the observed risk in the WPHC cohort. Results The observed five- and 10-year
      cardiovascular disease probability of the WPHC cohort was 10.0% (95% confidence
      interval (CI): 8.5-11.7) and 18.7% (95% CI: 16.7-21.0), respectively. The
      Framingham models significantly underestimated the cardiovascular disease risk
      for this cohort by around one-third, with a five-year cardiovascular disease risk
      estimate of 6.8% (95% CI: 6.4-7.2) and 10-year risk estimates of 12.0% (95% CI:
      11.4-12.6) and 14.2% (95% CI: 13.5-14.8). The original Framingham models showed
      good discrimination ability (C-statistic of 0.67) but a significant lack of
      calibration (chi2 between 82.56 and 134.67). After recalibration the 2008
      Framingham model corrected the underestimation and improved the calibration for
      five-year risk prediction (chi2 of 18.48). Conclusions The original Framingham
      models significantly underestimate the absolute cardiovascular disease risk for
      this Australian Indigenous population. The recalibrated 2008 Framingham model
      shows good performance on predicting five-year cardiovascular disease risk in
      this population and was used to calculate the first risk chart based on empirical
      validation using long-term follow-up data from a remote Australian Indigenous
      population.

PMID- 28749179
TI  - Analysis of microRNA expression and micronuclei frequency in workers exposed to
      vinyl chloride monomer in China.
AB  - AIM: To identify differently expressed miRNAs associated with vinyl chloride
      monomer (VCM) and micronuclei (MN) frequency. METHOD: In discovery stage, we used
      microarray to detect miRNAs expression in peripheral blood lymphocytes between
      six low and six high VCM-exposed workers grouped by medium cumulative exposure
      dose. Then we validated four miRNAs using real-time quantitative reverse
      transcription PCR (qRT-PCR) and detected the micronuclei frequencies using
      cytokinesis-block micronucleus assay in 94 VCM-exposed workers and 53 healthy
      control subjects. RESULTS & CONCLUSION: We found eight miRNAs significantly
      downregulated and seven miRNAs upregulated (|Fold Change| >2; p < 0.05) in the
      high-exposure group through microarray. We validate that miR-222-3p, miR-146a-5p
      and miR-151a-5p were downregulated, while miR-22-3p was upregulated in VCM
      exposed group (all p < 0.01). Furthermore, we found that expression of miR-22-3p
      was upregulated in the high micronuclei (MN) frequency subjects. In conclusion,
      our study suggested that these four miRNAs could be biomarkers of VCM exposure,
      and moreover miR-22-3p was correlated with MN frequency.

PMID- 28749182
TI  - Instructions for Contributors.

PMID- 28749183
TI  - Medicine and Art.

PMID- 28749184
TI  - Is cellular heterogeneity merely a confounder to be removed from epigenome-wide
      association studies?
AB  - Excitement about DNA methylation biomarkers has been tempered by a growing
      appreciation of the complex causal relations with cell fate. Intersample
      differences in DNA methylation can be partitioned into those that are independent
      of cellular heterogeneity and those that are caused by differential mixtures of
      cell types. Generally, the field has assumed that the former are more likely to
      be causative of disease. The latter has been considered a likely consequence of
      disease and a confounder to be removed. We argue that the conceptual separation
      of these signals is artificial and not necessarily informative about causation.
      DNA methylation is a very sensitive measure of cell fate mix and therefore
      reveals much about underlying disease etiology including aspects of causation.

PMID- 28749185
TI  - Internalised HIV-stigma, loneliness, depressive symptoms and sleep quality in
      people living with HIV.
AB  - OBJECTIVE: People living with HIV (PLWH) commonly report sleep disturbances which
      are associated with long-term health consequences, including disease progression.
      PLWH also experience internalised stigma as a result of their HIV status, which
      can be associated with increased loneliness and depression. Little attention
      focuses on the impact of these factors on sleep. Therefore, we examined whether
      internalised HIV-stigma was indirectly related to poorer sleep quality through
      higher levels of loneliness and depressive symptoms. DESIGN: 181 PLWH from across
      the United States completed an online survey. Main Study Measures: Internalised
      HIV-stigma was assessed using the HIV-Stigma Scale, loneliness was assessed using
      the UCLA-Loneliness Scale-Short Form, depressive symptoms were assessed with the
      Center for Epidemiologic Studies-Depression Index, and Sleep Quality was assessed
      using the Pittsburgh Sleep Quality Index. RESULTS: Internalised HIV-stigma was
      indirectly associated with poorer global sleep quality and daytime sleep
      dysfunction through both loneliness and depressive symptoms. CONCLUSIONS: PLWH
      who experience HIV-related stigma may experience greater feelings of loneliness,
      which are related to increased depressive symptoms and poorer sleep quality.
      Interventions focused on improving sleep in PLWH should focus on multiple factors
      that influence sleep, including psychosocial factors such as stigma, social
      isolation and depressive symptoms.

PMID- 28749186
TI  - Correlation between CAT polymorphism and susceptibility to DMAc-induced abnormal
      liver function: a case-control study of Chinese population.
AB  - CONTEXT: Acute or chronic exposure of N,N-dimethylacetamide (DMAc) is responsible
      for abnormal liver function. It appears that DMAc is mainly metabolized by
      cytochrome P450 in the liver and thereby produces reactive oxygen species (ROS).
      The elimination of ROS and the repairing of ROS-induced DNA damage are relevant
      to the ultimate toxicity of DMAc. OBJECTIVE: To investigate whether the
      polymorphisms in the CAT (rs564250, rs769214 and rs7943316), hOGG1 (rs2072668 and
      rs159153) and XRCC1 (rs25487 and rs1799782) genes are associated with
      susceptibility to DMAc-induced abnormal liver function in Chinese population.
      METHODS: Samples were obtained from 108 workers with DMAc-induced abnormal liver
      function and 108 workers with normal liver function. RESULTS: Subjects with the
      CAT rs769214 GA/GG genotypes had a reducing risk of abnormal liver function,
      which was more evident in the subgroups exposed to DMAc <10 years, exposed to
      DMAc <5 mg/m3, never smoked and never drank. CONCLUSIONS: CAT rs769214 (-844 G >
      A) polymorphism may be associated with DMAc-induced abnormal liver function in
      Chinese population.

PMID- 28749187
TI  - Differential methylation of lncRNA KCNQ1OT1 promoter polymorphism was associated
      with symptomatic cardiac long QT.
AB  - AIM: To investigate whether the differential methylation of KCNQ1OT1 was
      associated with the risk of symptomatic long QTc. PATIENTS & METHODS: We
      investigated the methylation status of KCNQ1OT1 in a cohort of patients (n = 131)
      with a symptomatic prolonged QTc. All the patients were genotyped for a common
      promoter polymorphism (rs11023840). They were also genotyped for DNA digested
      with the methylation-sensitive HpaII restriction enzyme. RESULTS: We found a
      significant higher frequency of AA genotype (p = 0.02) in the patients compared
      with healthy controls (n = 240). In the HpaII-digested samples there was a higher
      frequency of the A-allele among the patients compared with the controls (p =
      0.02). CONCLUSION: Our findings supported a role for the differential
      methylation/imprinting of KCNQ1OT1 in the risk for symptomatic prolonged QTc.

PMID- 28749188
TI  - Enteric coatings for colonic drug delivery: state of the art.

PMID- 28749189
TI  - Improved oral bioavailability for lutein by nanocrystal technology: formulation
      development, in vitro and in vivo evaluation.
AB  - Lutein is a kind of natural carotenoids possessing many pharmacological effects.
      The application of lutein was limited mainly due to its low oral bioavailability
      caused by poor aqueous solubility. Nanocrystal formulation of lutein was
      developed to improve the oral bioavailability in this study. The nanosuspension
      was prepared by the anti-solvent precipitation-ultrasonication method and
      optimized by Box-Behnken design, followed by freeze-drying to obtain lutein
      nanocrystals. The nanocrystals were characterized on their physical properties,
      in vitro dissolution and in vivo absorption performance. Lutein nanocrystals
      showed as tiny spheres with an average particle size of 110.7 nm. The result of
      diffractograms indicated that the percent crystallinity of lutein was 89.4% in
      coarse powder and then declined in nanocrystal formulation. The saturated
      solubility of lutein in water increased from 7.3 MUg/ml for coarse powder up to
      215.7 MUg/ml for lutein nanocrystals. The dissolution rate of lutein nanocrystals
      was significantly higher than that of coarse powder or the physical mixture. The
      Cmax and AUC0-24 h of lutein nanocrystals after oral administration in rats was
      3.24 and 2.28 times higher than those of lutein suspension, respectively. These
      results indicated that the nanocrystal formulation could significantly enhance
      the dissolution and absorption of lutein and might be a promising approach for
      improving its oral bioavailability.

PMID- 28749190
TI  - Are there any HOTTIPs for defining coding potential of lncRNAs, or just a lot of
      HOTAIR?

PMID- 28749191
TI  - Disease-related autoantibody profile in patients with systemic sclerosis.
AB  - BACKGROUND: Autoantibodies (autoAbs) help in diagnosis and predicting clinical
      phenotypes in systemic sclerosis (SSc). AIM OF THE STUDY: To determine the
      clinical utility of 13 SSc-related autoAbs in SSc patients. MATERIAL AND METHODS:
      A total of 131 consecutive patients with SSc (111 female, mean age 58.1 +/- 14
      years; 49 with diffused cutaneous SSc [dcSSc] and 82 with limited cutaneous SSc
      [lcSSc]) were analysed by a multiplex line immunoassay (Euroimmun) for
      autoantibodies (autoAbs) against 13 SSc-related antigens. A total of 22 patients
      with primary Raynaud phenomenon (RP), and 22 healthy controls were also analysed.
      RESULTS: ANA by indirect immunofluorescence was present in 128 (97.7%) patients
      with SSc. Excluding anti-Ro52, 113 (89.3%) SSc patients were positive for at
      least one autoAb: anti-Topoisomerase I (anti-Topo) I abs in 54 (41.2%), anti
      centromere proteins (anti-CENP) in 37 (28.2%, all reactive with centromere
      protein-A (CENPA) and centromere protein B (CENPB)), anti-RNA polymerase
      III(RP11) in 19 (14.5%), anti-RNA polymerase III(RP155) in 13 (9.9%), anti
      fibrillarin in 4 (3.1%), anti-Ku in 6 (4.6%), anti-nucleolus-organizing region
      (anti-NOR90) in 8 (6.1%), anti-PM-Scl100 in 2 (1.5%), and anti-PM-Scl75 in 4
      (3.1%). There was no immunoreactivity for Th/To or platelet-derived growth factor
      receptor (PDGFR). Overall, 102 (77.9%) SSc patients had autoAbs against Topo I,
      CENPA or CENPB, RP11 or RP155. Anti-Topo I abs were strongly associated with
      dcSSc, interstitial lung disease (ILD) (p < .001), pulmonary hypertension (PH) (p
      = .019) and ILD-PH (p = .003). Anti-CENPB abs were associated with lcSSc, and
      negatively associated with ILD. Anti-RP11 and anti-NOR90 abs were associated with
      male gender, and anti-NOR90 associated with ILD. CONCLUSIONS: Anti-Topo I, anti
      CENP, and anti-RNA pol III are the most prevalent autoAbs in SSc. Anti-Topo I and
      anti-NOR90 abs are associated with ILD and/or PAH.

PMID- 28749192
TI  - Current review of the SarQoL(r): a health-related quality of life questionnaire
      specific to sarcopenia.
AB  - INTRODUCTION: Sarcopenia, defined by a progressive and generalized loss of muscle
      mass and muscle function, is associated with many harmful clinical consequences.
      Several studies have reported the impact of sarcopenia on health-related quality
      of life (HRQoL) using generic quality of life (QoL) questionnaires. The results
      of these observational studies are quite heterogenous. Indeed, generic tools may
      not be able to detect subtle effects of sarcopenia on QoL. Recently, a sarcopenia
      specific HRQoL questionnaire was developed and validated in a population of
      sarcopenic subjects to more accurately assess the impact of sarcopenia on QoL.
      Areas covered: The purpose of this review is to present evidence regarding the
      impact of sarcopenia on QoL and to introduce a new specific HRQoL questionnaire,
      the SarQoL(r). Expert commentary: The self-administered SarQoL(r), initially
      developed in French, comprises 55 items translated into 22 questions. The
      questionnaire has been shown to be understandable, valid, consistent, and
      reliable and can therefore be recommended for clinical and research purposes. The
      questionnaire is now available in 11 different languages with another 20
      translations in progress. The instrument's sensitivity to change still needs to
      be assessed in future longitudinal studies.

PMID- 28749193
TI  - Validation of self-reported hearing loss among adult Croatians: the performance
      of the Hearing Self-Assessment Questionnaire against audiometric evaluation.
AB  - OBJECTIVE: The aim of this study was to validate the performance of a self
      assessment hearing loss screening tool for adults against audiometric evaluation.
      Different audiological measurements were compared with the results of a 10-item
      Likert-type questionnaire named the Hearing Self-Assessment Questionnaire (HSAQ)
      to investigate its psychometric characteristics. DESIGN: Participants underwent
      audiological evaluation and completed the HSAQ. The screening performance of the
      HSAQ was evaluated against three definitions of hearing loss: better-ear mean
      pure-tone thresholds >25 dBHL at 500-2000 Hz, 500-4000 Hz and 1000-4000 Hz. STUDY
      SAMPLE: The study enrolled 112 participants aged between 24 and 88 years (mean
      age 56.24 years, +/-12.92). RESULTS: The HSAQ had high Cronbach's alpha and
      intraclass correlation coefficients and showed construct, concurrent and
      discriminant validity. Its screening characteristics proved very good or
      excellent, depending on the definition of hearing loss. Receiver operating
      characteristic curve analysis showed excellent accuracy of the HSAQ in the
      identification of better-ear high-frequency hearing loss and better-ear speech
      frequency hearing loss, with respect to different cut-off points. CONCLUSIONS:
      Given the ease with which it is administered and its good screening properties,
      the HSAQ can be useful in deciding whether adult clients should be referred to
      audiological evaluation due to reasonable suspicion of hypoacusis.

PMID- 28749194
TI  - Results of preoperative chemoradiotherapy for patients with advanced cancer of
      the nasal cavity and paranasal sinuses.
AB  - OBJECTIVES: Curative treatment of nasal cavity and paranasal sinus cancer is
      challenging due to the proximity to critical anatomical structures. The purpose
      of this study was to analyze the impact of trimodality therapy with preoperative
      chemotherapy and reduced-dose radiotherapy followed by organ-preserving surgery
      for treating patients with nasal cavity and paranasal sinus cancer. METHODS: This
      retrospective study included all 156 patients diagnosed with sinonasal cancer in
      western Sweden between 1986 and 2009. We determined the treatment selection
      pattern and treatment outcomes for 79 patients treated with preoperative
      chemoradiotherapy. RESULTS: Squamous cell carcinoma was the most common
      histology. The five-year overall survival was 54%, and 85% of these patients had
      T3 or T4 tumors. The five-year cumulative incidence rate of local recurrence was
      32%. The five-year overall survival in patients with squamous cell carcinoma and
      adenocarcinoma was 45% and 76%, respectively. The median preoperative radiation
      dose was 48 Gy. Orbital exenteration was performed in 7% of patients.
      CONCLUSIONS: Preoperative chemoradiotherapy may be beneficial for patients with
      advanced sinonasal cancer when primary radical surgery is challenging. Survival
      outcomes were comparable to outcomes reported in the literature despite
      conservative surgery and relatively low radiation doses in patients with locally
      advanced tumors.

PMID- 28749195
TI  - Hippo pathway contributes to cisplatin resistant-induced EMT in nasopharyngeal
      carcinoma cells.
AB  - Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant tumor derived
      from the nasopharyngeal epithelium and is mainly prevalent in Southern China and
      Southeast Asia countries. Cisplatin (DDP) provides the first-line therapeutic
      administration in NPC patients. However, chemoresistance has been a main barrier
      and caused bad treatment outcome in NPC therapy. To understand the molecular
      mechanism of acquired resistance to DDP, multiple methods were performed to
      examine the morphocytology and molecular changes in DDP-resistant NPC cells. We
      found that drug resistance cells displayed epithelial-mesenchymal transition
      (EMT) characteristics. DDP-resistant NPC cells exhibited enhanced migration and
      invasion potential. Moreover, overexpression of TAZ, one key gene in Hippo
      pathway, is closely associated with the DDP resistance of NPC cells and its EMT
      properties. Depletion of TAZ in DDP-resistant cells reversed EMT phenotypes to
      MET characteristics and restored chemosensitivity of DDP-resistant cells to DDP
      treatment. These results suggest that inactivation of TAZ could be a promising
      approach for the treatment of NPC patients.

PMID- 28749196
TI  - Double-stranded telomeric DNA binding proteins: Diversity matters.
AB  - Telomeric sequences constitute only a small fraction of the whole genome yet they
      are crucial for ensuring genomic stability. This function is in large part
      mediated by protein complexes recruited to telomeric sequences by specific
      telomere-binding proteins (TBPs). Although the principal tasks of nuclear
      telomeres are the same in all eukaryotes, TBPs in various taxa exhibit a
      surprising diversity indicating their distinct evolutionary origin. This
      diversity is especially pronounced in ascomycetous yeasts where they must have co
      evolved with rapidly diversifying sequences of telomeric repeats. In this article
      we (i) provide a historical overview of the discoveries leading to the current
      list of TBPs binding to double-stranded (ds) regions of telomeres, (ii) describe
      examples of dsTBPs highlighting their diversity in even closely related species,
      and (iii) speculate about possible evolutionary trajectories leading to a long
      list of various dsTBPs fulfilling the same general role(s) in their own unique
      ways.

PMID- 28749197
TI  - Cardiovascular benefits and safety of non-insulin medications used in the
      treatment of type 2 diabetes mellitus.
AB  - Diabetes mellitus is a growing in exponential proportions. If the current growth
      trend continues, it may result in every third adult in the United States having
      diabetes mellitus by 2050, and every 10th adult worldwide. Type 2 diabetes
      mellitus (T2DM) confers a 2- to 3-fold increased risk of cardiovascular (CV)
      events compared with non-diabetic patients, and CV mortality is responsible for
      around 80% mortality in this population. Patients with T2DM can have other
      features of insulin resistance-metabolic syndrome like hypertension, lipid
      abnormalities, and obesity which are all associated with increased CV disease and
      stroke risk even in the absence of T2DM. The management of a T2DM calls for
      employing a holistic risk factor control approach. Metformin is the first line
      therapy for T2DM and has been shown to have cardiovascular beneficial effects.
      Intense debate regarding the risk of myocardial infarction with rosiglitazone led
      to regulatory agencies necessitating cardiovascular outcome trials with upcoming
      anti-diabetic medications. Glucagon like peptide-1 agonists and sodium glucose co
      transporter-2 inhibitors have shown promising CV safety and additional CV benefit
      in recent clinical trials. These drugs have favorable effects on traditional CV
      risk factors. The findings from these studies further support that fact that CV
      risk factor control plays an important role in reducing morbidity and mortality
      in T2DM patients. This review article will discuss briefly the cardiovascular
      safety and benefits of the oral medications which are currently being used for
      T2DM and will then discuss in detail about the newer medications being
      investigated for the treatment of T2DM.

PMID- 28749198
TI  - Empathy training in medical students - a randomized controlled trial.
AB  - AIM: Empathy is a core element in the doctor-patient relationship. This study
      examined whether empathy in medical students can be improved by specific
      training. METHODS: 158 medical students were randomized into two groups. The
      intervention group participated in an empathy skills training with simulated
      patients (SPs). The control group participated in a history course. After the
      intervention, empathy was assessed by blinded SPs and experts in an Objective
      Structured Clinical Examination (OSCE). Students also filled out a self
      assessment concerning their attitude on empathy (Jefferson Scale of Physician
      Empathy Student Version, JSPE-S-S). RESULTS AND CONCLUSIONS: Participants of the
      intervention group showed significantly higher levels of empathy when rated by
      SPs and experts than the control group. In contrast to that, no significant group
      differences were observed in self-rated empathy. The results underpin the value
      of empathy skills trainings in medical school study programs.

PMID- 28749199
TI  - Hair follicle-associated-pluripotent (HAP) stem cells.
AB  - Various types of stem cells reside in the skin, including keratinocyte progenitor
      cells, melanocyte progenitor cells, skin-derived precursors (SKPs), and nestin
      expressing hair follicle-associated-pluripotent (HAP) stem cells. HAP stem cells,
      located in the bulge area of the hair follicle, have been shown to differentiate
      to nerve cells, glial cells, keratinocytes, smooth muscle cells, cardiac muscle
      cells, and melanocytes. HAP stem cells are positive for the stem-cell marker
      CD34, as well as K15-negative, suggesting their relatively undifferentiated
      state. Therefore, HAP stem cells may be the most primitive stem cells in the
      skin. Moreover, HAP stem cells can regenerate the epidermis and at least parts of
      the hair follicle. These results suggest that HAP stem cells may be the origin of
      other stem cells in the skin. Transplanted HAP stem cells promote the recovery of
      peripheral-nerve and spinal-cord injuries and have the potential for heart
      regeneration as well. HAP stem cells are readily accessible from everyone, do not
      form tumors, and can be cryopreserved without loss of differentiation potential.
      These results suggest that HAP stem cells may have greater potential than iPS or
      ES cells for regenerative medicine.

PMID- 28749200
TI  - MM-GBSA and MM-PBSA performance in activity evaluation of AMPA receptor positive
      allosteric modulators.

PMID- 28749201
TI  - The nucleolus: A new home for the PIDDosome.

PMID- 28749202
TI  - Abbreviated breast MRI for screening women with dense breast: the EA1141 trial.
AB  - Early diagnosis improves survival of females with breast cancer. Mammographic
      screening improves early diagnosis of breast cancer. And yet, there appears to be
      room for improvement. Major shortcomings of mammographic screening are
      overdiagnosis of prognostically unimportant cancer, as well as underdiagnosis of
      cancers that are indeed relevant. Failure to detect biologically relevant breast
      cancer with mammographic screening is driven not only by host-related factors,
      i.e. breast tissue density, but also by tumour-related factors: Biologically
      relevant cancers may exhibit imaging features that render them indistinguishable
      from normal or benign breast tissue on mammography. These cancers will then
      progress to become the advanced-stage interval cancers observed in females
      undergoing mammographic screening. Since breast cancer continues to represent a
      major cause of cancer death in females, the search for improved breast cancer
      screening method continues. Abbreviated breast MRI has been proposed for this
      purpose because it will greatly reduce the cost associated with this method, due
      to a greatly reduced magnet time (down to 3 min), but especially also due to a
      greatly abridged image interpretation time, i.e. radiologist reading time. This
      commentary reviews the current situation and presents the EA1141 trial designed
      to investigate the utility of abbreviated breast MRI for screening average-risk
      females with dense breast tissue.

PMID- 28749203
TI  - CB002, a novel p53 tumor suppressor pathway-restoring small molecule induces
      tumor cell death through the pro-apoptotic protein NOXA.
AB  - P53 tumor suppressor gene mutations occur in the majority of human cancers and
      contribute to tumor development, progression and therapy resistance. Direct
      functional restoration of p53 as a transcription factor has been difficult to
      achieve in the clinic. We performed a functional screen using a bioluminescence
      based transcriptional read-out to identify small molecules that restore the p53
      pathway in mutant p53-bearing cancer cells. We identified CB002, as a candidate
      that restores p53 function in mutant p53-expressing colorectal cancer cells and
      without toxicity to normal human fibroblasts. Cells exposed to CB002 show
      increased expression of endogenous p53 target genes NOXA, DR5, and p21 and cell
      death which occurs by 16 hours, as measured by cleaved caspases or PARP. Stable
      knockdown of NOXA completely abrogates PARP cleavage and reduces sub-G1 content,
      implicating NOXA as the key mediator of cell death induction by CB002. Moreover,
      CB002 decreases the stability of mutant p53 in RXF393 cancer cells and an
      exogenously expressed R175H p53 mutant in HCT116 p53-null cells. R175H p53
      expression was rescued by addition of proteasome inhibitor MG132 to CB002,
      suggesting a role for ubiquitin-mediated degradation of the mutant protein. In
      summary, CB002, a p53 pathway-restoring compound that targets mutant p53 for
      degradation and induces tumor cell death through NOXA, may be further developed
      as a cancer therapeutic.

PMID- 28749204
TI  - Revision of a furosemide-loading vestibular-evoked myogenic potential protocol
      for detecting endolymphatic hydrops.
AB  - OBJECTIVE: The presence of endolymphatic hydrops can be suggested by improving
      the amplitude of vestibular-evoked myogenic potential (VEMP) after furosemide
      administration (furosemide loading VEMP [FVEMP]). The authors aimed to determine
      a stimulation frequency and judgment criteria to ascertain whether a revised
      FVEMP protocol can be applied to clinical settings. METHODS: The study included
      25 individuals with unilateral Meniere's disease (MD) and 11 normal healthy
      volunteers. Normalized amplitude of VEMP, using a tone burst sound at 250, 500,
      700, 1000, 1500 and 2000 Hz, was measured before and after furosemide
      administration in the two groups. Improvement ratio (IR) of amplitude was
      calculated at each frequency. RESULTS: There were no significant differences in
      IR between the control group and the MD group at each frequency, except at 500
      Hz. Receiver operating characteristic curve analysis revealed an IR cut-off value
      of 14.2% at 500 Hz, with a sensitivity of 0.706 and a specificity of 0.810.
      CONCLUSIONS: The revised FVEMP protocol using a 500 Hz tone burst stimulus and
      normalized amplitudes was defined as positive when IR exceeded 14.2% or when a
      biphasic wave could be detected after furosemide administration in cases without
      a detectable biphasic wave before administration.

PMID- 28749205
TI  - Esophageal endoscopic submucosal dissection using sodium hyaluronate is safe and
      effective.
AB  - BACKGROUND/AIMS: A submucosal cushion of sodium hyaluronate facilitates gastric
      and colorectal endoscopic submucosal dissection (ESD). However, few studies have
      evaluated the utility of sodium hyaluronate for ESD of esophageal lesions. The
      aim of this study is to evaluate the utility and safety of sodium hyaluronate for
      ESD of superficial esophageal squamous cell neoplasms (ESCN). MATERIAL AND
      METHODS: We retrospectively reviewed 111 ESCN in 86 patients treated by ESD
      between September 2007 and April 2013. There were four double cancers, with 107
      ESD procedures analyzed. RESULTS: The en bloc resection rate was 99% (106/107).
      The R0 resection rate was 93% (99/107). Of 106 specimens resected en bloc, four
      specimens had a positive horizontal margin, two specimens had non-assessable
      horizontal margins and one specimen had non-assessable horizontal and vertical
      margins. One patient with a non-assessable horizontal margin developed local
      recurrence seven months later, treated by repeat ESD. Delayed bleeding occurred
      in two procedures (2%), and intra-procedural perforation occurred in four (4%).
      None required operative repair. Endoscopy trainees performed 33 of 107 (31%) ESD
      procedures. Post-ESD stenosis requiring dilation occurred following five
      procedures (5%). CONCLUSIONS: Sodium hyaluronate for ESD of ESCN achieves a high
      R0 resection rate with a low rate of adverse events.

PMID- 28749206
TI  - Small-molecule CB002 restores p53 pathway signaling and represses colorectal
      cancer cell growth.
AB  - Much effort is currently focused on the p53 pathway. p53 is a key tumor
      suppressor, which is mutated or lost in many human cancers. Restoration of the
      p53 pathway holds the potential to induce selective cell death in tumor cells
      without harming normal cells that have intact p53 pathways. Most tumor cells
      express mutated p53 or suppress p53 by overexpression of MDM2. In this study, a
      compound referred to as CB002 with one closely related compound from the
      Chembridge library were evaluated for tumor cytotoxicity without affecting normal
      cells by restoration of the p53 pathway. A decrease of mutant p53 protein
      expression, restoration of inactivated p53, or some activation of p73 are
      candidate mechanisms this agent could cause tumor cell apoptosis and growth
      arrest. We further show that CB002 activates p53 pathway signaling in part via
      p73 in p53 mutant cancer cell lines. However, it is important to note that we
      have not established a role for p73 in the anti-tumor effect of CB002 or R1.
      CB002 causes tumor cell death with synergistic effects with traditional
      chemotherapeutics CPT-11 and 5-FU.

PMID- 28749207
TI  - Crothall VP Embraces Challenge of 'Dynamic Compliance Landscape'.

PMID- 28749210
TI  - Ask George.

PMID- 28749208
TI  - Ten Questions With ....

PMID- 28749211
TI  - A Roundtable Discussion: Advances in Patient Monitoring Translate to Improved
      Outcomes at the Bedside.

PMID- 28749212
TI  - Safety Innovations: Healthcare System Takes Bold Step with Continuous Monitoring.

PMID- 28749213
TI  - HTM Departments Should Operate like a Business.

PMID- 28749214
TI  - The Internet of Dangerous Things: A Complex Dialogue Worth Advancing.

PMID- 28749216
TI  - It's Time for Belts and Suspenders.

PMID- 28749217
TI  - Better Together: The Vital Role of Patients and End Users in Developing Safe and
      Effective Medical Devices.

PMID- 28749218
TI  - Responding to the Needs of Humans.

PMID- 28749219
TI  - The Roundup.

PMID- 28749221
TI  - On the Job: Time Management for Individuals with Diverse Work Responsibilities.

PMID- 28749222
TI  - Workplace Culture: 'Taking the Good with the Bad' Applies to Both Bosses and
      Employees.

PMID- 28749223
TI  - Anesthesia Gas Monitors: Function and General Troubleshooting.

PMID- 28749224
TI  - Army Medical Center Fortifies Training to Improve Efficiency.

PMID- 28749225
TI  - How to Write a Periodic Maintenance Procedure.

PMID- 28749226
TI  - Care of Preschoolers with Congenital Heart Disease by Kindergarten and Nursery
      Teachers in Japan.
AB  - The purpose of this study was to elucidate the involvement of kindergarten and
      nursery school teachers with young children with congenital heart disease. The
      study was designed as a qualitative descriptive study. Interviews of kindergarten
      and nursery school teachers with experience in the care and education of young
      children with congenital heart disease were conducted, during which they
      described their experience. Verbatim transcripts of the interviews were prepared,
      and the content was categorized. The study participants were 11 kindergarten and
      nursery school teachers. Extracted from the content of the interviews of the
      study participants were 282 codes, 33 subcategories, 6 categories, and 2 major
      categories. In their responses, the teachers indicated that they had been
      "Providing care for the children while seeking ways to avoid special treatment in
      a group setting." In addition, they established a "Framework for school-parent
      cooperation in order to promptly accommodate the wishes of parents" of these
      children. The study showed that the kindergarten and nursery school teachers
      involved other pupils and monitored the condition of children with congenital
      heart disease to avoid special treatment of the children in the group setting. In
      addition, the teachers established a framework for cooperation between the school
      and parents. In the future, these findings will be used to create a nursing
      support model for the group life of young children with congenital heart disease.

PMID- 28749227
TI  - Promoting Optimum Sexual Health of Children and Young People.
AB  - Emeritus Professor Alan Glasper, from the University of Southampton and Editor-in
      Chief of Comprehensive Child and Adolescent Nursing, discusses the quest by
      nurses to improve the sexual health of children and young people in contemporary
      society.

PMID- 28749228
TI  - "It Changed Everything. And Not All in a Bad Way": Reflections of Pediatric
      Cancer Experiences.
AB  - Pediatric cancer, otherwise known as childhood cancer, is devastating to both
      children and their families. All individuals in a family are often physically,
      psychologically, and socially affected. Using the qualitative theoretical
      orientation of interpretive phenomenology, interviews were conducted with 10
      pediatric cancer survivors and 9 of their support persons to gain a more holistic
      understanding of the pediatric cancer experiences of children and their families.
      A total of 4 themes emerged from the data, however only the past experiences of
      the survivors and their recollection of their pediatric journeys will be
      discussed. Survivors experienced a variety of negative effects during and after
      treatment, while their support persons explained the emotional upheaval they
      experienced while caring for their children. Further, all individuals recalled
      positive memories throughout their journeys. The results of this study provide
      health care professionals and school administrators with insight into how to
      manage the difficult transitions children with cancer face when returning to
      school after cancer diagnosis and/or treatment. As well, this study may allow
      others undergoing similar journeys to relate to the lived experiences of the
      participants in this work.

PMID- 28749229
TI  - Effects of a Support Program on Nurses' Communication with Hospitalized
      Children's Families.
AB  - More than a few pediatric nurses experience difficulty in communicating with
      children's family members. However, effective means of providing communication
      support for pediatric nurses have not been examined sufficiently. This study
      aimed to develop and implement a communication support program for nurses to
      facilitate improved communication with families of hospitalized children, and to
      clarify changes in nurses' recognition and behavior toward communication with
      families in clinical settings. The program lasted 6 months and consisted of
      lectures, role-play, 4 communication models in which nurses experienced
      difficulty communicating with family members, and continued individual support.
      The effects of the program were evaluated qualitatively and descriptively using
      semi-structured interviews. A total of 7 nurses with less than 5 years of
      pediatric nursing experience completed the program. Subsequent to program
      completion, nurses' awareness of careful communication with families increased,
      and they began to approach families actively using thoughtful words. Furthermore,
      as nurses received favorable reactions from families, they realized that
      communication was interactive and recognized that their perception of their
      communication skills as poor had changed. This program could contribute in
      reducing nurses' difficulty in communicating with families and encourage them to
      improve their communication.

PMID- 28749230
TI  - The History of Children's Nursing and Its Direction Within the United Kingdom.
AB  - This article presents an account of the "evolution of children's nursing." The
      pertinent topic was originally developed as part of a Doctorate in Education
      (EdD) as it was anticipated an understanding of children's nursing would provide
      a more comprehensive context for a doctoral study that aims to explore the
      child's experience of staying in Northern Ireland's regional children's hospital
      from the perspectives of children and children's nurses using child-centered
      methodology. Northern Ireland, England, Scotland, and Wales are the 4 countries
      collectively known as the United Kingdom (UK). Hence the concept of
      "children's/pediatric nursing" was extracted and presented as a catalogue of
      significant events in their order of occurrence. The article also considers the
      future direction of children's nursing within the UK. Wider dissemination was
      thought pivotal to inform all registered nurses, inclusive of those caring for
      children in all healthcare settings.

PMID- 28749231
TI  - Phase II study of concurrent chemoradiotherapy with a modified target volumes
      delineation method for inoperable oesophagealcancer patients.
AB  - OBJECTIVE: A Phase II study was designed to test the safety and efficacy of
      concurrent chemoradiotherapy with a modified target volumes delineation method
      for inoperable oesophageal cancer patients. METHODS: All eligible patients were
      treated with concurrent chemoradiotherapy. The method of delineating target
      volume is as follows: Planning gross target volume (PGTV) was defined as the
      primary gross tumour volume (GTV-t) plus a 3 cm margin longitudinally and a 0.5
      cm margin circumferentially, and positive lymph nodes(GTV-n) plus a 0.5 cm margin
      in all directions. Clinical target volume (CTV) was defined as PGTV plus a 0.5 cm
      margin in all directions and elective nodal region. Planning target volume (PTV)
      was defined as CTV plus a 0.5 cm margin in all directions. The dose of PGTV is 54
      60 Gy in 27-30 fractions(2Gy per fraction). The dose of PTV is 48.6-54 Gy in 27
      30 fractions(1.8Gy per fraction). The regimen consists of paclitaxel135 mgm-2 on
      1 day and DDP 25 mgm-2 on 3 days per 3 weeks. The patients received 2 cycles of
      chemotherapy during radiotherapy and 2-4 cycles of chemotherapy after
      radiotherapy. RESULTS: 34 patients were enrolled in this study. The median follow
      up time was 20.9 months (range: 3.7-28.4 months) for all patients. The 1- and 2
      year survival rates for all patients were 70.5 and 44.1%, respectively. Clinical
      complete response was observed in 21 patients(61.8%), cPR was observed in 9
      patients(26.5%) and cSD was observed in 4 patients(11.7%). CONCLUSION: This
      modified method with concurrent chemotherapy could achieve better locoregional
      control rate. The 1- and 2-year survival rates of this method were close to the
      survival rates of the current methods widely adopted. Advances in knowledge: The
      modified target volumes delineation method can enhance locoregional control rate
      of concurrent chemoradiotherapy.

PMID- 28749232
TI  - Behavioural and cognitive sex/gender differences in autism spectrum condition and
      typically developing males and females.
AB  - Studies assessing sex/gender differences in autism spectrum conditions often fail
      to include typically developing control groups. It is, therefore, unclear whether
      observed sex/gender differences reflect those found in the general population or
      are particular to autism spectrum conditions. A systematic search identified
      articles comparing behavioural and cognitive characteristics in males and females
      with and without an autism spectrum condition diagnosis. A total of 13 studies
      were included in meta-analyses of sex/gender differences in core autism spectrum
      condition symptoms (social/communication impairments and restricted/repetitive
      behaviours and interests) and intelligence quotient. A total of 20 studies were
      included in a qualitative review of sex/gender differences in additional autism
      spectrum condition symptoms. For core traits and intelligence quotient,
      sex/gender differences were comparable in autism spectrum conditions and typical
      samples. Some additional autism spectrum condition symptoms displayed different
      patterns of sex/gender differences in autism spectrum conditions and typically
      developing groups, including measures of executive function, empathising and
      systemising traits, internalising and externalising problems and play behaviours.
      Individuals with autism spectrum conditions display typical sex/gender
      differences in core autism spectrum condition traits, suggesting that diagnostic
      criteria based on these symptoms should take into account typical sex/gender
      differences. However, awareness of associated autism spectrum condition symptoms
      should include the possibility of different male and female phenotypes, to ensure
      those who do not fit the 'typical' autism spectrum condition presentation are not
      missed.

PMID- 28749233
TI  - Towards sex- and gender-informed autism research.

PMID- 28749234
TI  - The importance of critical life moments: An explorative study of successful women
      with autism spectrum disorder.
AB  - Ten women with autism spectrum disorder participated in oral interviews in order
      to share their experiences since their diagnosis and to discuss the factors that
      had enabled them to achieve success in different aspects of their life.
      Participants were encouraged to share their perspectives on their success and to
      discuss the challenges they encountered in their daily lives and how they
      overcame these. Interviews were analysed using a narrative-themed approach.
      Participants indicated that both internal and external factors enabled them to
      achieve success in different aspects of their lives. These included being an
      agent of change, a changed identity after diagnosis, experiencing the belief of
      others in their capability and seeing themselves as a mentor to others. Their
      experiences with overcoming obstacles in their lives enabled them to develop self
      efficacy and to shape their own success.

PMID- 28749236
TI  - Are males and females with autism spectrum disorder more similar than we thought?
AB  - Differences in behavioral and cognitive profiles have been suggested to
      potentially impact the presentation of social and communication symptoms in
      females with autism spectrum disorder. This study examined gender differences in
      age of diagnosis, cognitive profiles, social communication symptomatology, and
      autism spectrum disorder symptom severity in a community-based sample of 566
      males and 113 females with autism spectrum disorder ranging in age from 1 year, 9
      months to 56 years, 4 months. Results suggest either very small or no gender
      differences in age at diagnosis, intelligence quotient, cognitive profiles, or
      autism spectrum disorder symptom severity. This is a departure from clinical lore
      that females with autism spectrum disorder are more likely to have lower
      intelligence quotient and more severe impairments. There is a slight difference
      in symptom severity with females having higher average total Childhood Autism
      Rating Scale scores, but this difference is likely of minimal clinical
      significance. In contrast, on the Autism Diagnostic Observation Schedule-Generic,
      females were found to receive lower scores than males particularly on modules 2
      and 3. Across males and females, individuals with stronger verbal problem-solving
      skills were found to receive lower Autism Diagnostic Observation Schedule-Generic
      module 3 scores. Given the language demands of this module, additional attention
      may be warranted when evaluating older children and adolescents for autism
      spectrum disorder.

PMID- 28749237
TI  - Towards understanding the under-recognition of girls and women on the autism
      spectrum.

PMID- 28749238
TI  - Aesthetic and functional outcomes using a multiloop edgewise archwire for
      camouflage orthodontic treatment of a severe Class III open bite malocclusion.
AB  - Occasionally, orthodontists will be challenged to treat malocclusions and
      skeletal disharmonies, which by their complexity one might think that the only
      treatment alternative is the surgical-orthodontic approach. A male patient, aged
      17 years old, was diagnosed with a skeletal Class III malocclusion, anterior open
      bite and negative overjet. An unpleasant profile was the patient's 'chief
      complaint' showing interest in facial aesthetics improvement. Nevertheless, the
      patient and his parents strongly preferred a non-surgical treatment approach. He
      was treated with a multiloop edgewise archwire to facilitate uprighting and
      distal en-masse movement of lower teeth, correct the Class III open bite
      malocclusion, change the inclination of the occlusal plane and obtain the
      consequent morphological-functional adaptation of the mandible. The Class III
      malocclusion was corrected and satisfactory changes in the patient's profile were
      obtained. Active treatment was completed in 2 years, and facial result remained
      stable at 2 years 6 months after debonding.

PMID- 28749239
TI  - Methodological issues in a meta-analysis.

PMID- 28749241
TI  - Considerations for ADHD in the child with epilepsy and the child with migraine.
AB  - INTRODUCTION: Attention Deficit Hyperactivity Disorder (ADHD) is a common
      comorbid condition in children with epilepsy and migraine. Treatment of ADHD in
      children with epilepsy or migraine is essential but clinicians may overlook
      symptoms of ADHD and avoid appropriate use of medications that may reduce
      symptoms of ADHD without compromising treatment of epilepsy or migraine. Areas
      covered: PubMed was searched for articles on ADHD and epilepsy or migraine. Key
      papers were reviewed for additional articles. Areas of interest were:
      epidemiology, etiological factors, and treatment with emphasis on therapy. Expert
      commentary: Stimulant medication, especially methylphenidate, appears to be safe
      and effective in the treatment of ADHD in children with epilepsy or migraine.
      Unfortunately, data is limited with very few controlled trials of methylphenidate
      and very limited information on the use of amphetamines or non-stimulant drugs.

PMID- 28749240
TI  - Epigenetic dysregulation of the erythropoietic transcription factor KLF1 and the
      beta-like globin locus in juvenile myelomonocytic leukemia.
AB  - Increased levels of fetal hemoglobin (HbF) are a hallmark of more than half of
      the children diagnosed with juvenile myelomonocytic leukemia (JMML). Elevated HbF
      levels in JMML are associated with DNA hypermethylation of distinct gene promoter
      regions in leukemic cells. Since the regulation of globin gene transcription is
      known to be under epigenetic control, we set out to study the relation of DNA
      methylation patterns at beta-/gamma-globin promoters, mRNA and protein expression
      of globins, and epigenetic modifications of genes encoding the globin-regulatory
      transcription factors BCL11A and KLF1 in nucleated erythropoietic precursor cells
      of patients with JMML. We describe several altered epigenetic components
      resulting in disordered globin synthesis in JMML. We identify a cis-regulatory
      upstream KLF1 enhancer sequence as highly sensitive to DNA methylation and
      frequently hypermethylated in JMML. The data indicate that the dysregulation of
      beta-like globin genes is a genuine attribute of the leukemic cell clone in JMML
      and involves mechanisms not taking part in the normal fetal-to-adult hemoglobin
      switch.

PMID- 28749242
TI  - Interactive association between RhoA transcriptional signaling inhibitor, CCG1423
      and human serum albumin: Biophysical and in silico studies.
AB  - Multiple spectroscopic techniques, such as fluorescence, absorption, and circular
      dichroism along with in silico studies were used to characterize the binding of a
      potent inhibitor molecule, CCG1423 to the major transport protein, human serum
      albumin (HSA). Fluorescence and absorption spectroscopic results confirmed
      CCG1423-HSA complex formation. A strong binding affinity stabilized the CCG1423
      HSA complex, as evident from the values of the binding constant (Ka = 1.35 * 106
      5.43 * 105 M-1). The KSV values for CCG1423-HSA system were inversely correlated
      with temperature, suggesting the involvement of static quenching mechanism.
      Thermodynamic data anticipated that CCG1423-HSA complexation was mainly driven by
      hydrophobic and van der Waals forces as well as hydrogen bonds. In silico
      analysis also supported these results. Three-dimensional fluorescence and
      circular dichroism spectral analysis suggested microenvironmental perturbations
      around protein fluorophores and structural (secondary and tertiary) changes in
      the protein upon CCG1423 binding. CCG1423 binding to HSA also showed some
      protection against thermal denaturation. Site-specific marker-induced
      displacement results revealed CCG1423 binding to Sudlow's site I of HSA, which
      was also confirmed by the computational results. A few common ions were also
      found to interfere with the CCG1423-HSA interaction.

PMID- 28749243
TI  - Epidemiology and trend of pediatric adenoidectomy: a population-based study in
      Taiwan from 1997 to 2012.
AB  - OBJECTIVES: To assess population-level data for pediatric adenoidectomy. METHODS:
      Using data from the Taiwan National Health Insurance Research Database for the
      1997-2012 period, all inpatients <18 years who received adenoidectomies were
      identified by codes from the International Classification of Diseases, 9th
      Revision. RESULTS: A total of 20,599 children underwent adenoidectomy (mean age,
      7.4 years; 67% boys). The overall incidence rate was 24.5 per 100,000 children.
      The highest incidence was observed for the ages of 3-5 years in both genders (p <
      .001). Boys exhibited higher incidence rates than did girls (p < .001).
      Longitudinal data revealed an increase in the incidence rates from 1997
      (14.8/100,000) to 2012 (26.9/100,000) (p trend < .001). The proportion of
      adenoidectomies performed at medical centers decreased from 60.5 to 46.9%,
      whereas those performed at regional hospitals increased from 36.4 to 47.2% (all p
      trend < .001). The proportion of pediatric adenoidectomies performed for sleep
      disordered breathing (SDB) increased significantly from 10.1 to 35.6%, whereas
      those for infections decreased from 32.3 to 8.0% (all p trend < .001).
      CONCLUSIONS: This study revealed an increasing trend of pediatric inpatient
      adenoidectomy incidence rates during 1997-2012 in Taiwan. Moreover, surgical
      indications have shifted from infections to SDB.

PMID- 28749244
TI  - Radiation protection and mitigation potential of phenylbutyrate: delivered via
      oral administration.
AB  - PURPOSE: Phenylbutyrate (PB), a histone deacetylase inhibitor (HDACi) has
      demonstrated radiation protection in both in vitro and in vivo models. Studies
      previously demonstrated that PB and other HDAC inhibitors could inhibit radiation
      lethality in vivo by subcutaneous (s.c) injection. The objective of this study
      was to test the ability of oral PB treatment to protect against or to mitigate
      acute gamma radiation-induced lethality in vivo. MATERIALS AND METHODS: Human
      osteoblasts cells were used to evaluate radiation survival when PB was delivered
      pre- or post-radiation. A 30-day radiation lethality study was used to assess the
      radioprotective (pre-radiation) and radiomitigative (post-radiation) capability
      of PB. Possible mechanisms evaluated were antioxidant activity effects, HDAC
      inhibition, DNA damage, and hematological recovery. RESULTS: Treatment of HOS
      cells with PB 50 MUM either before or after radiation increased radiation
      resistance as assessed by clonogenic survival. Western blot studies showed that
      PB treatment acetylated histones in vivo and ameliorated the radiation-induced
      reduction in acetylated histone-4 (H4). Pre-radiation oral administration of PB
      (10 mg/kg) provided radioprotection against gamma radiation (7-11.5 Gy) with a
      dose reduction factor of 1.25 (p = 0.001). PB oral administration post-radiation
      provided moderate radiation mitigation against gamma radiation (7-11.5 Gy) and
      demonstrated a dose reduction factor of 1.18 (p = 0.05). PB pre-radiation and
      post-radiation treatment was associated with significant elevations in
      neutrophils and platelets and attenuation of DNA damage. CONCLUSIONS: These
      results indicate that oral PB has potential as a radiation protector and a
      radiation mitigator and that potential mechanisms of action include attenuation
      of DNA damage, antioxidant activity, and bone marrow protection.

PMID- 28749245
TI  - Advances in our understanding of immunization and vaccines for patients with
      systemic lupus erythematosus.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune
      disease. In SLE, immune system dysfunction is postulated to result by virtue of
      the disease itself as well as by the impact of treatment modalities employed. A
      myriad of immune dysregulations occur including complement system dysfunction
      among others. Infectious agents are known to complicate the disease course in
      close to 25-45% of SLE patients. Areas covered: In this review a discussion of
      the immunogenicity and safety of viral and bacterial vaccinations in SLE was
      performed. The search included ISI Web of Science (WoS), Scopus, MEDLINE/PubMed,
      Google-Scholar, DOAJ, EbscoHOST, Scirus, Science Direct, Cochrane Library and
      ProQuest. Proper string made up of a key-words including 'SLE', 'vaccination',
      'safety' and 'efficacy' was used. Expert commentary: Vaccination of SLE patients
      is proven to be immunogenic. Concerns regarding vaccine safety are postulated,
      yet no direct relationship between vaccination and disease exacerbation were
      established. While live virus vaccines are generally contraindicated in
      immunosuppressive states, generally live attenuated vaccinations are recommended
      in SLE patients on a case-to-case basis. In SLE patients, clinical parameters
      such as vaccination during disease exacerbations have not been intensively
      studied and therefore while apparently safe, vaccination is generally recommended
      while disease is quiescent.

PMID- 28749246
TI  - Identification of more potent imipridones, a new class of anti-cancer agents.

PMID- 28749247
TI  - Evaluating the effectiveness of a community-based hygiene promotion program in a
      rural Salvadoran setting.
AB  - There has been considerable progress in the reduction of diarrheal disease among
      children under five through health and nutrition interventions. However,
      diarrheal disease is still the second leading cause of child death worldwide.
      There is growing recognition that comprehensive hygiene behavior improvements
      should be integral to prevention efforts, but the effectiveness of different
      approaches for hygiene promotion is still being established. Hygiene risk
      practices vary across settings, suggesting that prevention strategies should be
      adapted to local contexts using community-based approaches. We planned,
      implemented, and evaluated a hygiene promotion intervention using the hygiene
      cluster framework. The two-year, multi-level intervention was implemented by
      local health promoters who were involved in identifying and addressing disease
      transmission risks at the household, school, and community levels. The
      intervention was evaluated using a quasi-experimental pretest-posttest design
      with repeated follow-up assessments to determine changes in hygiene knowledge and
      behavior. A household survey instrument was administered at three time points in
      the intervention ( n = 480) and comparison ( n = 271) communities to assess two
      hygiene knowledge and eleven hygiene behavior outcome variables. We used one-way
      analysis of variance with post hoc analysis using Tukey's HSD for multiple
      comparisons to examine change and differences over time. We also fit a linear
      regression model to identify statistically significant differences. Study results
      demonstrated improvements in the areas of: knowledge of disease transmission and
      key times for handwashing, water container hygiene, sanitation practices,
      personal hygiene and food hygiene. The hygiene cluster framework is useful for
      hygiene promotion intervention planning and evaluation, and we recommended
      continued testing of this framework across contexts. We also recommend local
      community participatory approaches, as well as in-depth formative behavioral
      assessments by hygiene cluster that also consider environmental barriers to
      behavior change.

PMID- 28749248
TI  - Update in perioperative medicine: practice changing evidence published in 2016.
AB  - This summary reviews 18 key articles published in 2016 which have significant
      practice implications for the perioperative medical care of surgical patients.
      Due to the multi-disciplinary nature of the practice of perioperative medicine,
      important new evidence is published in journals representing a variety of medical
      and surgical specialties. Keeping current with the evidence that drives best
      practice in perioperative medicine is therefore challenging. We set out to
      identify, critically review, and summarize key evidence which has the most
      potential for practice change. We integrated the new evidence into the existing
      body of medical knowledge and identified practical implications for real world
      patient care. The articles address issues related to anticoagulation, transfusion
      threshold, immunosuppressive medications, postoperative delirium, myocardial
      injury after noncardiac surgery, postoperative pain management, perioperative
      management of antihypertensives, perioperative fasting, and perioperative
      diabetic control.

PMID- 28749249
TI  - An autopsy-verified case of steroid-responsive encephalopathy with convulsion and
      a false-positive result from the real-time quaking-induced conversion assay.
AB  - We report an autopsy-verified case of steroid-responsive encephalopathy with
      convulsion and a false-positive result from the real-time quaking-induced
      conversion (RT-QUIC) assay. A 61-year-old Japanese man presented with acute onset
      of consciousness disturbance, and convulsions, but without a past medical or
      family history of progressive dementia, epilepsy, or prion disease. Brain
      diffusion and fluid-attenuated inverted recovery MR images revealed edematous
      cortical hyper-intensity, which diminished after the acute phase. Steroid pulse
      therapy was partially effective, although he continued to have dementia with
      myoclonus and psychiatric symptoms, despite resolution of the consciousness
      disturbance. Cerebrospinal fluid (CSF) analysis revealed a normal cell count,
      with significantly elevated levels of 14-3-3 protein and total tau protein. In
      addition, prion protein in the CSF was slowly amplified by the RT-QUIC assay.
      PRNP gene analysis revealed methionine homozygosity at codon 129 without
      mutation. The patient died of sudden cardiac arrest at 3 months after the onset
      of symptoms. The positive result from the RT-QUIC assay led us to suspect
      involvement of prion disease, although a postmortem assessment revealed that he
      had pathological changes after convulsion, and no prion disease. This case
      indicates that convulsion may cause false-positive RT-QUIC results, and that a
      postmortem evaluation remains the gold standard for diagnosing similar cases.

PMID- 28749250
TI  - Discovery of thalicthuberine as a novel antimitotic agent from nature that
      disrupts microtubule dynamics and induces apoptosis in prostate cancer cells.
AB  - We report for the first time the mechanism of action of the natural product
      thalicthuberine (TH) in prostate and cervical cancer cells. TH induced a strong
      accumulation of LNCaP cells in mitosis, severe mitotic spindle defects, and
      asymmetric cell divisions, ultimately leading to mitotic catastrophe accompanied
      by cell death through apoptosis. However, unlike microtubule-binding drugs
      (vinblastine and paclitaxel), TH did not directly inhibit tubulin polymerization
      when tested in a cell-free system, whereas it reduced cellular microtubule
      polymer mass in LNCaP cells. This suggests that TH indirectly targets microtubule
      dynamics through inhibition of a critical regulator or tubulin-associated
      protein. Furthermore, TH is not a major substrate for P-glycoprotein (Pgp), which
      is responsible for multidrug resistance in numerous cancers, providing a
      rationale to further study TH in cancers with Pgp-mediated treatment resistance.
      The identification of TH's molecular target in future studies will be of great
      value to the development of TH as potential treatment of multidrug-resistant
      tumors.

PMID- 28749251
TI  - Identification of spirocyclic or phosphate substituted quinolizine derivatives as
      novel HIV-1 integrase inhibitors: a patent evaluation of WO2016094197A1,
      WO2016094198A1 and WO2016154527A1.
AB  - INTRODUCTION: Highly active antiretroviral therapy (HAART) has been widely
      adopted to control the HIV-1 infection successfully. HIV-1 integrase (IN)
      inhibitors are primary drugs in HAART regimens targeting integration step in the
      HIV-1 life cycle. However, due to the emergence of viral resistance and cross
      resistance amongst drugs, there is a pressing need for new and potent IN
      inhibitors. This review covers the three patents describing spirocyclic and
      phosphate substituted quinolizine derivatives as novel HIV-1 IN inhibitors for
      the discovery of new anti-HIV-1 drug candidates. Areas covered: This review is
      focused on spirocyclic and phosphate substituted quinolizine derivatives bearing
      the same metal chelation scaffold as novel HIV-1 IN inhibitors. Expert opinion:
      Generally, privileged structure-based optimizations have emerged as an effective
      approach to discover newly antiviral agents. More generally, due to the similar
      Mg2+ catalytic active centers of endoribonucleases, some divalent metal ion
      chelators were found to be versatile binders targeting multiple metalloenzymes.
      Therefore, privileged structure-based scaffold re-evolution is an important
      tactic to identify new chemotypes, to explore unknown biological activities, or
      to provide effective ligands for multiple targets by modifying the existing
      active compounds.

PMID- 28749252
TI  - The role of Dickkopf-1 as a potential prognostic marker in pancreatic ductal
      adenocarcinoma.
AB  - Dickkopf-1(DKK-1), the downstream target of beta-catenin/T-cell factor,
      participates in a negative feedback loop in the Wnt signaling and reported as an
      important biomarker in many tumors. In this study, we analyzed the expression of
      DKK-1 in pancreatic ductal adenocarcinoma (PDAC) patients at both mRNA and
      protein levels. We used real-time PCR to detect the expression of DKK-1 in 32
      PDAC and paired adjacent non-tumor tissues, results suggested that the expression
      of DKK-1 was increased in PDAC tissues. We found the similar results in the
      analysis of 3 independent microarray data sets. Immunohistochemical staining of
      311 pairs of PDAC tissues suggested that DKK-1 expression was significantly
      associated with T classification (P = 0.039) and lymph node metastasis (P =
      0.035). Furthermore, Kaplan-Meier analysis for DKK-1 expression demonstrated that
      patients with higher DKK-1 level had shorter overall survival (OS) and relapse
      free survival (RFS) time in Ren Ji cohort and online PDAC database at both mRNA
      and protein levels. Univariable and multivariable Cox regression analysis
      confirmed that DKK-1 as well as lymph node metastasis and histology were
      independent predictors of OS in patients with PDAC. This study demonstrated that
      DKK-1 may be a predictor for prognosis in PDAC patients.

PMID- 28749253
TI  - Randomized crossover study investigating daily versus on-demand vulvar Visnadine
      spray in women affected by female sexual arousal disorder.
AB  - The aim of the study was to verify the efficacy of vulvar Visnadine spray in
      premenopausal women affected by female sexual arousal disorder (FSAD). Thirty
      eight women aged 25-40 years affected by FSAD were enrolled in the randomized
      crossover study, by two possible sequences: on-demand, washout, daily (A
      sequence); and daily, washout, on-demand (B sequence). The Female Sexual Function
      Index (FSFI) and the Female Sexual Distress Scale (FSDS) were used to assess
      sexual function and sexual distress, respectively. Color Doppler ultrasonography
      was used to measure clitoral blood flow. The study had two follow-ups at 30 (T1)
      and 60 days (T2). Thirty-one women completed the study. Mean (SD) sexual activity
      and vulvar Visnadine spray usage was 1 +/- 0.9 weekly during on-demand
      administration for both the sequences (Vs T0, p = NS). The mean sexual activity
      during daily usage was 2 +/- 0.9 (Vs T0, p < .004) and 2 +/- 0.8 (Vs T0, p <
      .001) for A and B sequences, respectively. FSFI total score, particularly genital
      arousal, improved more during the daily than during on-demand phases of both
      sequences (p < .001). Finally, clitoral blood flow improved significantly during
      daily usage of both the sequences (p < .001). Our study suggests that vulvar
      Visnadine spray could improve sexual performance of women affected by FSAD,
      producing changes in subjective and objective sexual aspects.

PMID- 28749254
TI  - Individualised training at different intensities, in untrained participants,
      results in similar physiological and performance benefits.
AB  - This study compared effects of training at moderate, high, or a combination of
      the two intensities (mixed) on performance and physiological adaptations, when
      training durations were individualised. Untrained participants (n = 34) were
      assigned to a moderate, high, or mixed group. Maximal oxygen uptake (VO2max),
      power output at VO2max (MAP), time-to-exhaustion and gross efficiency were
      recorded before and after four weeks of cycling training (four times per week).
      The moderate group cycled at 60% MAP in blocks of 5 min with 1 min recovery, and
      training duration was individualised to 100% of pre-training time-to-exhaustion.
      The high group cycled at 100% MAP for 2 min with 3 min recovery, and training
      duration was set as the maximum number of repetitions completed in the first
      training session. The mixed group completed two moderate- and two high-intensity
      sessions each week, on alternate days. VO2max, MAP, and time-to-exhaustion
      increased after training (P < 0.05), but were not different between groups (P >
      0.05). The mixed group improved their gross efficiency at 50% MAP more than the
      other two groups (P = 0.044) after training. When training is individualised for
      untrained participants, similar improvements in performance and physiological
      measures are found, despite marked differences in exercise intensity and total
      training duration.

PMID- 28749255
TI  - PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS
      (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES.
AB  - Aspergillosis is a common respiratory fungal disease in African penguins (
      Spheniscus demersus ) under managed care, and treatment failures with
      itraconazole due to drug resistance are increasingly common, leading to recent
      use of voriconazole. Empirical dosing with voriconazole based on other avian
      studies has resulted in adverse clinical drug effects in penguins. The objective
      of this study was to determine oral voriconazole pharmacokinetics (PK) in African
      penguins (n = 18). Single and once daily multiple oral doses of 5 mg/kg
      voriconazole were evaluated with a 4-mo washout period between trials. Plasma
      voriconazole concentrations were determined via high-performance liquid
      chromatography. Data was modeled using 3-compartamental population methodologies
      that supported first-order elimination. Observed mean peak concentration (1.89
      MUg/ml) after single dosing PK analysis was determined within the first hour
      following voriconazole administration. In the multiple-dose trial average plasma
      voriconazole concentrations were significantly higher on days 4 and 7 as compared
      with day 2. The mean estimates for volume of distribution (V/F) and clearance
      (Cl/F) for the multiple-dose study were 3.34 L and 0.18 L/hr, respectively. Monte
      Carlo simulations determined the median area under the curve (AUC0-24) at 84 hr
      was 37.7 MUg.h/ml. As this assessment was comparable with the average AUC in
      humans receiving the recommended human oral dosage 200 mg b.i.d., it suggests
      that 5 mg/kg p.o. s.i.d. could be a safe and effective regimen in African
      penguins for treatment of aspergillosis. However, due to potential drug
      accumulation and subsequent toxicity, therapeutic drug monitoring with dosage
      adjustments is recommended to individualize dosing.

PMID- 28749256
TI  - ECHOCARDIOGRAPHIC FINDINGS OF BIDIMENSIONAL MODE, M-MODE, AND DOPPLER OF
      CLINICALLY NORMAL BLACK-RUMPED AGOUTI (DASYPROCTA PRYMNOLOPHA, WAGLER 1831).
AB  - The black-rumped agouti ( Dasyprocta prymnolopha , Wagler 1831) is currently
      under intense ecologic pressure, which has resulted in its disappearance from
      some regions of Brazil. Echocardiography is widely used in veterinary medicine
      but it is not yet part of the clinical routine for wild animals. The objective of
      the present study was to assess the applicability of the echocardiographic exam
      in nonanesthetized agouti and to establish normal reference values for
      echocardiographic measurements in bidimensional mode (2D), M-mode, and Doppler
      for this species, and a lead II electrocardiogram was simultaneously recorded.
      Twenty agouti were used in this study. All the echocardiographic measurements
      were positively correlated with weight (P < 0.05), and there were no significant
      differences between sexes (P > 0.05). Blood flow velocities in the pulmonary and
      aortic artery ranged from 67.32-71.28 cm/sec and 79.22-101.84 cm/sec,
      respectively. The isovolumic relaxation time was assessed in all the animals and
      ranged from 38.5 to 56.6 ms. The maximum value for the nonfused E and A waves and
      the Et and At waves was 158 beats/min for both. The results obtained for the
      morphologic and heart hemodynamic measurements can guide future studies and help
      in the clinical management of these animals in captivity.

PMID- 28749257
TI  - FIRST RECORD OF HEMATOLOGIC VALUES IN FREE-LIVING AND CAPTIVE MANED SLOTHS
      (BRADYPUS TORQUATUS; XENARTHA, BRADYPODIDAE).
AB  - Bradypus torquatus is a rare and endemic sloth species from the Atlantic Forest,
      Brazil. Due to a lack of medical information including hematologic reference
      parameters for the species, hematologic baseline values were determined using
      samples from 14 clinically healthy B. torquatus , under captive (n = 7) and free
      living (n = 7) conditions in Bahia State, Brazil. Additionally, the morphology of
      the blood cells is presented, with a demonstration that the Barr body chromosome
      may assist with sex determination of the species. The Barr body chromosome was
      present in all seven females and absent in all males. Many erythrocytes were
      approximately the size of small lymphocytes, with red blood cells exhibiting
      anisocystosis, normochromia, and apparent macrocytosis, compared with domestic
      animals. This study provides the first published hematologic values and cell
      morphology for B. torquatus . However, further studies are suggested using an
      automated hematology analyzer with larger sample sizes so that reference
      intervals may be established and hematologic values better understood for sex,
      habitat type, and age cohorts.

PMID- 28749258
TI  - COELOMIC TERATOMA IN A BLUE-AND-YELLOW MACAW (ARA ARARAUNA).
AB  - A 2-mo-old, female blue-and-yellow macaw (Ara ararauna) presented with severe
      abdominal distension, pain, and respiratory distress. Ultrasonographic
      examination detected a heterogeneous mass with multiple anechoic areas,
      compatible with a multilocular cyst, occupying most of the coelomic cavity.
      Postmortem examination revealed a mass of 12.0 * 8.5 * 5.0 cm, which had an
      irregular surface and was connected by a pedicle to the ileum. This mass
      compressed and displaced the liver, proventriculus, gizzard, and intestines
      cranially to the left. The cut surface was lobulated, gray-white, mildly firm or
      soft, and was interspersed with multiple cysts filled with viscous and opaque
      liquid. Microscopically, it was composed of well- differentiated embryonic
      tissues from the endoderm, mesoderm, and ectoderm; therefore, it was diagnosed as
      a mature teratoma, which was theorized to have originated from Meckel's
      diverticulum. This study is the first, to the authors' knowledge to report a case
      of a teratoma in a blue-and-yellow macaw.

PMID- 28749259
TI  - MANAGEMENT OF PODODERMATITIS WITH AN ORTHOTIC BOOT IN A SOUTHERN ISABELA GIANT
      TORTOISE (CHELONOIDIS VICINA).
AB  - A 62-yr-old male Southern Isabela giant tortoise (Chelonoidis vicina) had a 1-yr
      history of chronic, reoccurring pododermatitis on the palmar surface of the left
      forelimb. Aggressive wound management was instituted and included surgical
      debridement, vacuum-assisted closure, and orthotic boot support during healing. A
      custom fabricated, carbon fiber clamshell Charcot Restraint Orthotic Walker
      walking boot was utilized to reduce focal pressure over the wound during weight
      bearing and promote a more normal gait. Distal padding was used to distribute
      pressure on the palmar surface of the left forelimb, with a focal depression in
      the padding preventing pressure directly over the wound. The design and trim
      lines were adjusted to allow shoulder and elbow motion without impingement. The
      clamshell design allowed relatively easy removal for wound inspection and
      dressing changes. The wound ultimately resolved after 9 wk of management with the
      orthotic boot, with no reoccurrence over the next 3 yr.

PMID- 28749260
TI  - PIGMENTED VILLONODULAR SYNOVITIS IN A RETICULATED GIRAFFE (GIRAFFA
      CAMELOPARDALIS).
AB  - : A 17-yr-old, female, captive-born reticulated giraffe ( Giraffa camelopardalis
      ) presented with acute-onset lameness of the right metacarpophalangeal (fetlock)
      joint. Despite multiple courses of treatment, the lameness and swelling
      progressively worsened over a 3.5-yr period, and the giraffe was euthanized. At
      necropsy, gross and microscopic changes in the right, front fetlock and
      associated flexor tendon sheath included villous synovial hyperplasia and the
      formation of discrete pigmented nodules within synovial membranes.
      Histologically, the nodules were composed of abundant, fibrous connective tissue
      with heavy macrophage infiltration, hemosiderin deposition, and distinctive,
      multinucleated cells that resembled osteoclasts. These findings were consistent
      with pigmented villonodular synovitis (PVNS), a rare condition affecting both
      humans and animals. Although the pathophysiology of PVNS is poorly understood,
      lesions exhibit features of both neoplastic and reactive inflammatory processes.
      This case report represents, to the authors' knowledge, the first description of
      PVNS in a nondomestic ungulate.

PMID- 28749261
TI  - COLONIC ADENOCARCINOMAS IN A FAMILIAL GROUP OF CAPTIVE AMUR RAT SNAKES (ELAPHE
      SCHRENCKI).
AB  - This article reports five cases of colonic adenocarcinomas in a family group of
      captive Amur rat snake (Elaphe schrenckii) from the Reserve Africaine de Sigean,
      France. This tumor was detected in three females and two males, all adults, and
      accounted for 16% of causes of death of adults of this species at this
      institution from 1986 to 2013. Grossly, mild to marked thickening of the
      intestinal wall cranially to the cloaca was found in four cases; tan to yellow
      firm masses were noted in the distal intestinal wall in the other case.
      Microscopically, neoplasms were characterized by infiltrating, poorly
      circumscribed, and unencapsulated nests of epithelial cells. Marked anisokaryosis
      and anisocytosis were seen in all neoplasms. The etiology of the neoplasms was
      not determined, but the familial clustering suggests a common etiologic factor.

PMID- 28749262
TI  - MYCOBACTERIUM INTRACELLULARE INFECTION CAUSING A RETROPERITONEAL MASS IN A
      BINTURONG (ARCTICTIS BINTURONG).
AB  - A 19-yr-old castrated male binturong ( Arctictis binturong ) with a history of
      recurrent pyogranulomatous panniculitis, lymphangitis, and dermatitis was
      presented for evaluation of hyporexia and tenesmus. A large caudal abdominal mass
      was palpated on physical examination. On ultrasound, the mass encircled and
      obstructed the left ureter, resulting in hydroureter and hydronephrosis. The
      animal was euthanized, and necropsy revealed a large retroperitoneal pyogranuloma
      with acid-fast organisms identified in both the mass and the perineal skin. The
      acid-fast organisms within the retroperitoneal mass were identified as
      Mycobacterium intracellulare by PCR. This case represents an unusual presentation
      of M. intracellulare in a novel species.

PMID- 28749263
TI  - MEASURING INTRAOCULAR PRESSURE IN WHITE'S TREE FROGS (LITORIA CAERULEA) BY
      REBOUND TONOMETRY: COMPARING DEVICE, TIME OF DAY, AND MANUAL VERSUS CHEMICAL
      RESTRAINT METHODS.
AB  - Ocular diseases reported in frogs include uveitis and glaucoma, which are
      associated with changes in intraocular pressure (IOP). The objectives of this
      study were to characterize the normal IOP for White's tree frogs ( Litoria
      caerulea ) using two types of rebound tonometers, and to assess whether time of
      day or method of restraint affected IOP. Eighteen conscious, unrestrained,
      ophthalmologically normal frogs were used to measure IOP using TonoVet(r) and
      TonoLab(r) tonometers, at three time points during the day. In a subset of 12
      frogs, IOP was measured while under manual restraint using the TonoVet.
      Anesthesia was induced in 9 frogs using two different concentrations of MS-222
      (0.5 g/L and 2 g/L) in order to evaluate for changes in IOP with the TonoVet.
      Mean (+/- SD) IOP values for the TonoLab (16.8 +/- 3.9 mm Hg) were significantly
      higher than TonoVet values (14.7 +/- 1.6 mm Hg; P < 0.01). TonoVet IOP values did
      not significantly change with time of day. TonoLab values were significantly
      lower in the evening (1600-1800; 14.5 +/- 3.1 mm Hg), compared with morning and
      midday measurements (0800-1000 and 1200-1400; 18.0 +/- 3.8 mm Hg; P < 0.01).
      Manually restrained frogs had significantly lower IOP (13.4 +/- 1.5 mm Hg)
      compared with unrestrained frogs (15.3 +/- 1.2 mm Hg; P < 0.01). Chemical
      restraint did not cause significant changes in IOP. Intraocular pressure can be
      measured with both types of rebound tonometers in White's tree frogs, but time of
      day and manual restraint can affect IOP values.

PMID- 28749264
TI  - PULMONARY LESIONS CAUSED BY THE LUNGWORM (DIDELPHOSTRONGYLUS HAYESI) IN THE
      OPOSSUM (DIDELPHIS VIRGINIANA) IN COLIMA, MEXICO.
AB  - Didelphostrongylus hayesi is an important and prevalent pulmonary nematode in the
      opossum ( Didelphis virginiana ). An in-depth description of the pulmonary
      lesions caused by this nematode is lacking. The objective of this investigation
      was to make a detailed account of the gross, subgross, and microscopic changes
      that occur in the lungs of opossums naturally infected with D. hayesi. Forty-four
      opossums trapped in the state of Colima, Mexico, were euthanized by an overdose
      of barbiturates. Following a postmortem examination, the right lung was cut from
      the main bronchi and placed in a Petri dish containing a saline solution for the
      detection and identification of live parasites. The left lung was fixed and cut
      serially for subgross microscopic examination and sections of lung were cut and
      stained for histopathologic examination. The most remarkable gross change in
      parasitized lungs was a poorly collapsible pulmonary parenchyma and mild
      emphysema. The right lung tested positive for lungworms on gross examination in
      20/44, and 11/44 (25%) of the left lungs showed tan nodules on the pleural
      surface. Microscopically, the bronchi of 20/44 animals harbored adult and larval
      stages of D. hayesi (left lung), the same 20 opossums from which nematodes were
      grossly evident at necropsy (right lung). Adults and larvae were present in
      bronchi, bronchioles, and alveoli mixed with desquamated cells and many
      eosinophils, and to a lesser extent neutrophils, alveolar macrophages, and giant
      cells. Bronchi and bronchioles exhibited goblet cell hyperplasia and metaplasia
      respectively, and infiltration of lymphoplasmacytic cells in the interstitium and
      lamina propria. The tan nodules consisted of focal alveolar endogenous lipidosis,
      which likely resulted from parasitic airway obstruction. The lungs of 3/20
      parasitized opossums also showed alveolar bronchiolization (Lambertosis). The
      absence of Eucoleus aerophilus or bacterial pneumonia incriminates D. hayesi as
      the putative cause of pulmonary lesions in these opossums.

PMID- 28749265
TI  - EMERGENCY ANESTHESIA AND EXPLORATORY LAPAROTOMY IN A COMPROMISED PACIFIC WHITE
      SIDED DOLPHIN (LAGENORHYNCHUS OBLIQUIDENS).
AB  - Anesthesia and surgery in cetaceans have inherent risks and have rarely been
      utilized as viable treatment options. This report represents the first known
      multidisciplinary team approach to emergency laparotomy in a compromised, 22-yr
      old, female Pacific white-sided dolphin ( Lagenorhynchus obliquidens ). The
      inciting clinical signs and ancillary diagnostics were consistent with a
      mechanical ileus. Although no torsion or obstruction was apparent during surgery,
      severe enteritis and peritonitis were noted. Postoperatively, the animal was
      maintained on aggressive medical management with continuous supportive care until
      succumbing 3 days later with clinical pathology indicative of terminal sepsis and
      profound inflammation. Postmortem findings included generalized vascular stasis
      and segmental intestinal volvulus with infarction. To the authors' knowledge,
      this is one of the most-complex surgical and anesthetic procedures performed in a
      cetacean. Though the outcome was unsuccessful, this case represents the aquatic
      veterinary community's collective advances in the ability to treat cetaceans
      under human care.

PMID- 28749266
TI  - EPIDEMIOLOGIC EVALUATION OF ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 3B INFECTION IN
      AN AFRICAN ELEPHANT (LOXODONTA AFRICANA).
AB  - This epidemiologic study follows a 5-yr-old male African elephant ( Loxodonta
      africana ) during an episode of hemorrhagic disease (HD) due to elephant
      endotheliotropic herpesvirus 3B (EEHV3B) utilizing data from complete blood
      counts, electrophoresis and acute phase protein analysis, and polymerase chain
      reaction (PCR) of multiple body fluids during and after the clinical episode. The
      elephant presented with sudden onset of marked lethargy and inappetence followed
      by hypersalivation, hyperemia of the conjunctivae and focally on the tongue, and
      swellings on the head and ventrum. A moderate leukocytopenia with band
      neutrophilia, lymphopenia, monocytopenia, and thrombocytophilia was followed by a
      rise in all three cell types by day 10. Moderate increases in serum amyloid A and
      C-reactive protein were noted in the first weeks of illness. Conventional PCR of
      whole blood yielded a strong positive result for EEHV3B. Quantitative PCR
      revealed moderate viremia, which slowly returned to undetectable levels by day 35
      of treatment. EEHV3B was shed in trunk wash samples starting at day 22 for 10
      days at moderate levels, and then at low levels for up to 8.5 mo. All three
      female herd mates shed low levels of EEHV3B in trunk washes intermittently
      starting from day 28 of the calf's illness until over 7 mo afterward. The
      majority of saliva samples from the calf over the 8.5-mo period were also
      positive for EEHV3B. A subfraction of saliva samples from a female herdmate was
      positive from days 127-190 following disease onset in the calf. Four elephant
      gammaherpesviruses were detected sporadically from the calf and female herdmates
      during this same time period. Treatment was started at the onset of clinical
      signs and consisted of rectal and oral fluids and oral famciclovir. This is the
      first case of EEHV3B HD in an elephant species and the first thorough
      epidemiologic evaluation of EEHV HD in an African elephant.

PMID- 28749267
TI  - COMPARISON OF ISOFLURANE AND SEVOFLURANE FOR SHORT-TERM ANESTHESIA IN MEERKATS
      (SURICATA SURICATTA)-ARE THERE BENEFITS THAT OUTWEIGH COSTS?
AB  - Meerkats ( Suricata suricatta ) are routinely anesthetized with isoflurane in zoo
      and field settings. Twenty healthy adult meerkats of mixed age and sex held in
      the Zoological Society of London's collection were anesthetized with 4%
      isoflurane by face mask for routine health examinations. The procedure was
      repeated 5 mo later in the same group of animals utilizing sevoflurane at 5% for
      induction, and again 3 mo later with sevoflurane at 6.5% for induction to
      approximate equipotency with isoflurane. The speed and quality of induction and
      recovery were compared between the two volatile anesthetic agents. There was no
      statistically significant difference in the speed of induction across any of the
      anesthetic regimes. There was a significant difference in recovery times between
      isoflurane and 6.5% sevoflurane (427 +/- 218 and 253 +/- 65 sec, respectively
      [mean +/- SD]). Under the conditions of this study, sevoflurane at 6.5% induction
      dose resulted in better quality induction and recovery than sevoflurane at 5%
      induction or isoflurane. The mean heart and respiratory rates during anesthesia
      were higher using 5% sevoflurane for induction but there was no significant
      difference in either rate between isoflurane and sevoflurane used at a 6.5%
      induction dose. This study suggests that sevoflurane at a dose of 6.5% for
      induction and 4% for maintenance is a safe and effective anesthetic agent in
      healthy adult meerkats. Rapid return to normal behavior after anesthesia is
      important in all zoo species but particularly so in animals with a complex social
      and hierarchical structure such as meerkats. For this species, the advantage
      afforded by the speed of recovery with sevoflurane may offset the cost in certain
      circumstances.

PMID- 28749268
TI  - DETECTION OF BARTONELLA SP. IN DEER LOUSE FLIES (LIPOPTENA MAZAMAE) ON GRAY
      BROCKET DEER (MAZAMA GOUAZOUBIRA) IN THE NEOTROPICS.
AB  - Louse flies or deer keds, Lipoptena spp., are widespread in Neotropical cervids,
      but the vector-borne pathogens of louse flies had only been previously reported
      in the Northern hemisphere. This is the first report of Bartonella spp. in deer
      louse flies (Lipoptena mazamae) in the neotropics collected from gray brocket
      deer ( Mazama gouazoubira ) in Southern Brazil. DNA from Bartonella sp. was
      detected in all 429 L. mazamae collected from 11 road-killed gray brocket deer.
      The same sequences of DNA of Bartonella spp. were identified in samples. Gray
      brocket deer are abundant in Brazil, so Bartonella-infected Lipoptena spp. may be
      widely distributed in the neotropics.

PMID- 28749269
TI  - EPITHELIOTROPIC INTESTINAL T-CELL LYMPHOMA IN A HARBOR SEAL (PHOCA VITULINA).
AB  - A 14-yr- old, male harbor seal ( Phoca vitulina ) presented with depression,
      anorexia, and weight loss. Clinical examination revealed no specific
      abnormalities. Diagnostic imaging displayed an enlarged mass in the dorso-cranial
      abdomen. The animal was euthanized due to progressive worsening of symptoms.
      Grossly, severe emaciation and a massive enlargement of one mesenteric lymph node
      were found. Microscopically, a neoplastic round cell population with morphologic
      characteristics of mature lymphocytes infiltrated the mesenteric lymph node as
      well as the jejunal mucosa and exhibited a marked invasion of the mucosal
      epithelial layer. Immunohistochemically, the majority of cells expressed CD3, but
      not CD79alpha, indicating a T-cell origin of the tumor cells. Microscopic as well
      as immunohistochemical findings enabled the diagnosis of an epitheliotropic
      intestinal T-cell lymphoma, a neoplasm that has yet not been described in a
      harbor seal.

PMID- 28749270
TI  - HEALTH SURVEY INCLUDING SELECTED BLOOD PARAMETERS IN THE AFRICAN SLENDER SNOUTED
      CROCODILE (MECISTOPS CATAPHRACTUS) AT THE ABIDJAN ZOO IN COTE D'IVOIRE.
AB  - The Zoo National d'Abidjan (Abidjan Zoo) in Cote d'Ivoire, West Africa, holds the
      world's largest captive population of African slender-snouted crocodiles
      (Mecistops cataphractus, formerly Crocodylus cataphractus), at 36 adults, 16
      yearlings, and 23 hatchlings. Twelve yearling and 12 adult slender-snouted
      crocodiles at the Abidjan Zoo were restrained for physical exam, body condition
      scoring, and venipuncture in September 2015. Blood samples collected from the
      supravertebral venous sinus were analyzed using a handheld blood analyzer
      (Abaxis(r) I-stat, Abaxis, Inc., Union City, California 94587, USA) with Chem8+
      cartridges (CLIAwaived, Inc., San Diego, California 92130, USA). The adult
      crocodiles appeared in good general health and demonstrated blood values similar
      to those of other reptiles. The yearlings had low, ionized calcium values and low
      hematocrit and hemoglobin levels compared with the adult crocodiles and to other
      crocodile reference ranges. These findings may dramatically improve the health of
      the crocodiles and help to ensure a thriving captive population of this
      critically endangered species.

PMID- 28749271
TI  - EVALUATION OF HUSBANDRY AND MORTALITY IN LESSER HEDGEHOG TENRECS (ECHINOPS
      TELFAIRI).
AB  - Causes of morbidity and mortality for various species of tenrecs have not been
      widely published, aside from several reports of neoplasia, and these data are
      crucial for advancing objectives for preventive medicine, diagnosis, and
      treatment. A survey on husbandry, morbidity, and mortality of lesser hedgehog
      tenrecs ( Echinops telfairi ) in Association of Zoos and Aquariums (AZA)
      institutions was conducted. Out of 32 institutions, 20 responded with data for 98
      living and 93 dead animals. The most common causes of mortality among the dead
      animals were neoplasia (24%), hepatic lipidosis (11%), septicemia (8.6%),
      pneumonia (8.6%), cardiomyopathy (7.5%), renal disease (6.5%), osteomyelitis
      (3.2%), and trauma (3.2%). There was no statistically significant correlation
      between sex and neoplasia. Data about educational usage were specifically
      provided by survey respondents for 50 of the tenrecs, with only 42% being
      excluded from educational programming. Tenrecs are common to many AZA
      institutions as both educational and exhibit animals, and this study provides a
      helpful reference for expected health problems and highlights the need for future
      investments into medical diagnosis and treatment for these animals.

PMID- 28749272
TI  - KETAMINE-MEDETOMIDINE AND KETAMINE-MEDETOMIDINE-MIDAZOLAM ANESTHESIA IN CAPTIVE
      CHEETAHS (ACINONYX JUBATUS)-COMPARISON OF BLOOD PRESSURE AND KIDNEY BLOOD FLOW.
AB  - Six clinically healthy captive cheetahs ( Acinonyx jubatus ) were anesthetized
      twice using two different drug combinations to investigate if blood pressure and
      kidney blood flow are affected by medetomidine dosage. Protocol KM (2.0 mg/kg
      ketamine and 0.05 mg/kg medetomidine) was compared with protocol KMM (2.0 mg/kg
      ketamine, 0.02 mg/kg medetomidine, and 0.1 mg/kg midazolam). Heart rate (HR),
      respiratory rate (RR), body temperature, end-tidal carbon dioxide pressure
      (ETCO2), and anesthetic depth were monitored every 10 min. Noninvasive mean
      (MAP), systolic (SAP), and diastolic (DAP) arterial blood pressure were measured,
      and Duplex Doppler ultrasonography was performed on the kidneys. The mean
      arterial resistive index (RI) was determined and the pulse pressure index (PPI)
      was calculated, as indicators for kidney blood flow. There were no significant
      differences in induction and recovery times. MAP was significantly higher with KM
      than KMM at 35 min, and in both protocols decreased significantly after
      atipamezole administration. DAP was significantly higher at 25 and 35 min in
      animals anesthetized with KM; it also decreased significantly with both protocols
      after atipamezole administration. The PPI was significantly lower throughout the
      procedure with KM, and with both protocols increased significantly after
      atipamezole administration. Both the higher blood pressure and the reduced PPI
      with KM were likely a direct effect of the higher medetomidine dosage, and these
      findings indicate that lower medetomidine dosages might reduce hypertension and
      lead to a better PPI in cheetah immobilization.

PMID- 28749273
TI  - A RETROSPECTIVE REVIEW OF WESTERN LOWLAND GORILLA (GORILLA GORILLA GORILLA)
      MORTALITY IN EUROPEAN ZOOLOGIC COLLECTIONS BETWEEN 2004 AND 2014.
AB  - An understanding of the main causes of mortality among captive gorillas is
      imperative to promoting their optimal care, health, and welfare. A retrospective
      observational review of mortality among the European zoo-housed western lowland
      gorilla ( Gorilla gorilla gorilla) population from 2004 to 2014 was carried out.
      This is the first published study of mortality in this population. Relevant
      postmortem data were requested from each collection reporting a death during the
      study period. Age at death enabled grouping into discrete age categories. Deaths
      were classified according to cause. The main causes of death overall and for each
      age category and sex were identified. In total, 151 gorillas from 50 European
      collections died during the study period. Postmortem data were available for 119
      (79%) of the deaths, of which 102 (86%) were classified by cause. Diseases of the
      digestive system were responsible for most (23%) deaths overall. Also of
      significance (each accounting for 15% overall mortality) were deaths due to
      external causes (especially trauma) among young gorillas and cardiovascular
      disease among adult and aged animals. Being a male gorilla was associated with an
      8.77- and 5.40-fold increase in risk of death due to cardiovascular and
      respiratory disease, respectively. Death due to external causes was 4.45 times
      more likely among females than males. There was no statistically significant
      difference in life expectancy between male and female gorillas. The authors
      conclude that further work is needed to understand risk factors involved in the
      main causes of death and suggest a need for standardization with regard the
      approach to postmortem examination and data collection, sample collection, and
      storage across European zoos.

PMID- 28749274
TI  - EVALUATION OF THE I-STAT PORTABLE CLINICAL ANALYZER FOR MEASUREMENT OF IONIZED
      CALCIUM AND SELECTED BLOOD CHEMISTRY VALUES IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS).
AB  - Thei-STAT(r) portable clinical analyzer (PCA) provides patient-side results for
      hematologic, biochemical, and blood gas values when immediate results are
      desired. This analyzer is commonly used in nondomestic animals; however,
      validation of this method in comparison with traditional benchtop methods should
      be performed for each species. In this study, the i-STAT PCA was compared with
      the Radiometer ABL 800 Flex benchtop analyzer using 24 heparinized whole blood
      samples obtained from healthy E. maximus . In addition, the effect of sample
      storage was evaluated on the i-STAT PCA. Analytes evaluated were hydrogen ion
      concentration (pH), glucose, potassium (K+), sodium (Na+), bicarbonate (HCO3-),
      total carbon dioxide (TCO2), partial pressure of carbon dioxide (PCO2), and
      ionized calcium (iCa2+). Statistical analysis using correlation coefficients,
      Passing-Bablok regression analysis, and Bland-Altman plots found good agreement
      between results from samples run immediately after phlebotomy and 4 hr
      postsampling on the i-STAT PCA with the exception of K+, which is known to change
      with sample storage. Comparison of the results from the two analyzers at 4 hr
      postsampling found very strong or strong correlation in all values except K+,
      with statistically significant bias in all values except glucose and PCO2.
      Despite bias, mean differences assessed via Bland-Altman plots were clinically
      acceptable for all analytes excluding K+. Within the reference range for iCa2+,
      the iCa2+ values obtained by the i-STAT PCA and Radiometer ABL 800 Flex were
      close in value, however in light of the constant and proportionate biases
      detected, overestimation at higher values and underestimation at lower values of
      iCa2+ by the i-STAT PCA would be of potential concern. This study supports the
      use of the i-STAT PCA for the evaluation of these analytes, with the exception of
      K+, in the Asian elephant.

PMID- 28749275
TI  - CLINICAL CHALLENGE: THE ENDOLYMPHATIC SYSTEM IN THE DENNY'S TREE FROG
      (POLYPEDATES DENNYSI).

PMID- 28749276
TI  - OBSTETRICAL AND POSTPARTUM COMPLICATIONS IN LESSER MADAGASCAR HEDGEHOG TENRECS
      (ECHINOPS TELFAIRI): FOUR CASES.
AB  - Currently, little is known about diseases and health concerns in tenrecs, family
      Tenrecidae. During the past 10 yr of breeding lesser Madagascar hedgehog tenrecs
      ( Echinops telfairi ) at a single zoological institution, a diverse range of
      obstetric and postpartum complications have been observed: pyometra, metritis,
      retained fetal membranes, retained fetus, perinatal mortality, and maternal
      neglect with subsequent successful hand-rearing of neonates. Treatment of these
      problems is complicated in tenrecs because of their small size and secretive
      behavior. Some of the cases reported in this article had successful resolution by
      ovariohysterectomy or cesarean section. The four cases described in this report
      overall help to disseminate options and outcomes for the diagnosis, treatment,
      and management of obstetric and postpartum complications in this small,
      secretive, nondomestic species.

PMID- 28749277
TI  - CASE SERIES: CLINICAL SALMONELLOSIS IN FOUR BLACK RHINOCEROS (DICEROS BICORNIS)
      CALVES.
AB  - Although Salmonella spp. infection has been identified in captive and free
      ranging rhinoceros, clinical cases in black rhinoceros ( Diceros bicornis )
      calves have not been described. This case series describes clinical salmonellosis
      in four black rhinoceros calves. Two calves developed self-limiting diarrhea,
      recovering after treatment. The other two cases were fatal. One of the fatal
      cases had a short clinical course, whereas the other case was protracted, with
      signs reflecting multiple organ system involvement. In all cases, diagnosis was
      by fecal culture and/or quantitative polymerase chain reaction. A variable
      clinical presentation, which is typical for salmonellosis in domestic hoofstock,
      was a feature of these rhinoceros cases. Similarly, postmortem pathology in black
      rhinoceros calves was consistent with domestic neonatal ungulates with
      salmonellosis. Potential predisposing factors for infection were considered to be
      primiparity of the dam and failure of passive transfer in the calf. The case
      investigation included attempts to identify the source of infection, which was
      aided by organism serotyping. In one case, the patient's dam and another
      conspecific in the facility were shown to be asymptomatic shedders of the
      organism strain responsible for disease in the calf. Further surveillance of
      captive rhinoceros Salmonella spp. carrier status is needed to inform screening
      recommendations for this taxa.

PMID- 28749278
TI  - SURVEY OF ANAPLASMA PHAGOCYTOPHILUM ANTIBODIES IN CAPTIVE PRZEWALSKI'S HORSES
      (EQUUS FERUS PRZEWALSKII).
AB  - Anaplasma phagocytophilum (formerly Ehrlichia equi ) is a tickborne pathogen of
      domestic horses and the causative agent of equine granulocytic anaplasmosis.
      After the occurrence of clinical anaplasmosis in a Przewalski's horse ( Equus
      ferus przewalskii) housed at the Smithsonian Conservation Biology Institute in
      2008, opportunistic serosurveillance of the herd was initiated. From 2008 to
      2014, 57 serum samples were collected from 27 individuals (10 males; 17 females).
      Using indirect immunofluorescent antibody assays for anti- Anaplasma
      phagocytophilum antibodies, it was determined that prevalence was 53%. No
      significant sex differences were identified. A statistical association between
      increasing age and seropositive status suggests cumulative risk of exposure to
      Anaplasma phagocytophilum . After exclusion of four clinical cases of
      anaplasmosis, it was found that 22-57% of those sampled each year were
      seropositive and clinically normal, suggesting that the majority of Przewalski's
      horses develop subclinical or self-limiting anaplasmosis after exposure to A.
      phagocytophilum .

PMID- 28749279
TI  - EFFECTS OF TRAMADOL ON THE MINIMUM ANESTHETIC CONCENTRATION OF ISOFLURANE IN
      WHITE-EYED PARAKEETS (PSITTACARA LEUCOPHTHALMUS).
AB  - The aim of this study was to determine the minimum anesthetic concentration (MAC)
      of isoflurane, and to investigate if tramadol changes the isoflurane MAC in white
      eyed parakeets (Psittacara leucophthalmus). Ten adult birds weighing 157 +/- 9 g
      were anesthetized with isoflurane in oxygen under mechanical ventilation.
      Isoflurane concentration for the first bird was adjusted to 2.2%, and after 15
      min an electrical stimulus was applied in the thigh area to observe the response
      (movement or nonmovement). Isoflurane concentration for the subsequent bird was
      increased by 10% if the previous bird moved, or decreased by 10% if the previous
      bird did not move. This procedure was performed serially until at least four
      sequential crossover events were detected. A crossover event was defined as a
      sequence of two birds with different responses (positive or negative) to the
      electrical stimulus. Isoflurane MAC was calculated as the mean isoflurane
      concentration value at the crossover events. After 1 wk, the same birds were
      reanesthetized with isoflurane and MAC was determined at 15 and 30 min after
      intramuscular administration of 10 mg/kg of tramadol using the same method. A
      paired t-test (P < 0.05%) was used to detect significant differences for MAC
      between treatments. Isoflurane MAC in this population of white-eyed parakeets was
      2.47 +/- 0.09%. Isoflurane MAC values 15 and 30 min after tramadol administration
      were indistinguishable from each other (pooled value was 2.50 +/- 0.18%); they
      were also indistinguishable from isoflurane MAC without tramadol. The isoflurane
      MAC value in white-eyed parakeets is higher than reported for other bird species.
      Tramadol (10 mg/kg, i.m.) does not change isoflurane MAC in these birds.

PMID- 28749280
TI  - ATTEMPTED SURGICAL CORRECTION OF A PERSISTENT RIGHT FOURTH AORTIC ARCH IN A
      JUVENILE ROTHSCHILD'S GIRAFFE (GIRAFFA CAMELOPARDALIS ROTHSCHILDI).
AB  - A 5-mo-old female Rothschild's giraffe ( Giraffa camelopardalis rothschildi)
      presented for regurgitation. Esophagoscopy at 24 wk of age revealed a markedly
      dilated cranial esophagus with a tight stricture at the level of the heart base
      consistent with a vascular ring anomaly. Surgical exploration confirmed
      persistent right fourth aortic arch with ductus originating from left subclavian
      artery at its junction with the aorta and left subclavian artery. The patent
      ductus arteriosus was surgically ligated. The procedure was complicated by
      limited surgical access and vascular friability resulting in uncontrollable
      hemorrhage, and the animal was euthanatized. The animal's large size and unique
      shape precluded preoperative examination by computed tomography. Surgical
      accessibility was poor because cranial retraction of the thoracic limb was
      limited. Histology revealed focal degeneration of the aorta and subclavian artery
      and muscular degeneration of the esophagus. Degeneration was attributed to local
      hypoxia from compression by the vascular structure as the animal grew.

PMID- 28749281
TI  - NEOPLASIA IN SNAKES AT ZOO ATLANTA DURING 1992-2012.
AB  - A retrospective study was conducted to review neoplasia of captive snakes in the
      Zoo Atlanta collection from 1992 to 2012. Of 255 snakes that underwent necropsy
      and histopathologic examination at Zoo Atlanta during the study period, 37 were
      observed with neoplasia at necropsy. In those 37 snakes, 42 neoplastic lesions of
      18 primary cell types were diagnosed. Thirty-five of those neoplasms (83.3%) were
      malignant, and of those, 19 were of mesenchymal origin, whereas 14 were of
      epithelial origin. The median annual rate of neoplasia at necropsy was 12.5%
      (interquartile range = 2.8-19.5%) over the 21-yr study period. The mean estimated
      age at death for snakes with neoplasia was 13.2 yr (range, 1-24 yr).
      Investigating the incidence and clinical significance of neoplasia in captive
      snakes is vital for developing effective preventative and treatment regimes.

PMID- 28749282
TI  - ORONASAL SQUAMOUS CELL CARCINOMAS IN FRANCOIS' LANGURS (TRACHYPITHECUS
      FRANCOISI).
AB  - Squamous cell carcinomas (SCCs) are common oronasal tumors in nonhuman primates.
      In this study, 11 cases of oronasal SCC in Francois' langurs ( Trachypithecus
      francoisi ) are described. Five initial cases were discovered on review of the
      North American Francois' langur studbook, with a potential familial pattern
      observed. The studbook was used to identify related individuals, and records were
      requested for review. Six additional cases were documented, and samples from all
      cases were submitted for microscopic review, as well as polymerase chain reaction
      (PCR), immunohistochemistry (IHC), and in situ hybridization (ISH), for generic
      papillomaviruses and PCR for herpesviruses because either virus may cause SCC in
      humans and other nonhuman primates. Affected langurs commonly presented with
      facial swelling or ocular discharge but frequently did not have clinical signs,
      and carcinomas were diagnosed during routine examinations. Carcinomas were
      located in the oral or nasal cavities affecting the oral mucosa, tongue, hard
      palate, or oropharynx. Histologically, SCCs comprised anastomosing cords and
      nests of neoplastic epithelial cells that differentiated synchronously and
      asynchronously from peripheral basal type cells to central squamous-type cells
      and were occasionally oriented around accumulations of necrotic cell debris.
      Nuclear pleomorphism, anisokaryosis, prominent nucleoli, occasional mitoses, and
      a scirrhous response were common features. All animals tested negative for both
      viruses, except two langurs that were positive for generic papillomavirus by PCR,
      but no papillomavirus was detected by either IHC or ISH. In most cases, affected
      animals died within 5 mo of diagnosis.

PMID- 28749283
TI  - SEROPREVALENCE AND MOLECULAR CHARACTERIZATION OF FERLAVIRUS IN CAPTIVE VIPERS OF
      COSTA RICA.
AB  - Ferlaviruses (FV, previously referred to as ophidian paramyxoviruses, OPMV), are
      enveloped viruses with a negative-strand RNA genome, affecting snakes in
      captivity worldwide. Infection is characterized by respiratory and nervous
      clinical signs and carries high mortality rates, but no specific treatment or
      vaccine is currently available. Costa Rica has 16 species of vipers, found in
      captivity in collections essential for antivenom production, reintroduction, and
      public education. FV circulation in these populations was previously unknown, and
      the risk of introducing the viruses into naive collections or free-ranging
      populations exists if the virus's presence is confirmed. The objective of this
      study was to determine seroprevalence and FV shedding in 150 samples from captive
      vipers in nine collections across Costa Rica. A hemagglutination inhibition (HI)
      assay was performed to determine the antibody titer against two Ferlavirus
      strains, Bush viper virus (BV) and Neotropical virus (NT), and reverse
      transcriptase polymerase chain reaction (RT-PCR) and sequencing to determine
      virus secretion in cloacal swabs. Ferlavirus strains were replicated in Vero
      cells, and chicken anti-FV polyclonal antibodies were produced and used as a
      positive control serum for the HI. Results demonstrate that seroprevalence of
      anti-FV antibodies in viper serum was 26.6% (n = 40) for the BV strain and 30% (n
      = 45) for the NT strain in the population tested. Furthermore, molecular
      characterization of FV group A was possible by sequencing the virus recovered
      from three cloacal swabs, demonstrating circulation of FV in one collection. This
      study demonstrates for the first time serological evidence of FV exposure and
      infection in vipers in captivity in Costa Rica, and suggests cross reactivity
      between antibodies against both strains. Appropriate biosafety measures could
      prevent the spread of FV between and within collections of reptiles in the
      country.

PMID- 28749284
TI  - MEDIASTINAL LYMPHOMA AND CHYLOTHORAX IN A STRIPED SKUNK (MEPHITIS MEPHITIS).
AB  - Tumors are infrequently reported in skunks, with only a few case reports
      published in the literature. Chylothorax associated with mediastinal lymphoma was
      diagnosed in a captive 7-yr-old male striped skunk ( Mephitis mephitis ). The
      animal presented with anorexia and apathy. Supportive care and prednisolone
      improved the animal's clinical status for 2 wk preceding its death.
      Histopathology supported the clinical findings, and the tumor was classified as a
      mediastinal non-Hodgkin lymphoma, stage 2b, which has not been documented in the
      literature.

PMID- 28749285
TI  - DIAGNOSIS OF PREGNANCY IN BARBARY SHEEP (AMMOTRAGUS LERVIA) USING A BOVINE ASSAY
      FOR PREGNANCY-ASSOCIATED GLYCOPROTEINS.
AB  - Pregnancy diagnosis is an important part in reproduction management of wild
      ruminants involved in free-ranging and captive programs. Pregnancy-associated
      glycoproteins (PAGs) are placenta-expressed proteins released into maternal blood
      circulation. Tests with high specificity have been developed and validated in
      domestic species and have been used in some wild ungulate species. One hundred
      and seventeen serum samples collected from 72 mature female Barbary sheep (
      Ammotragus lervia ) were tested using a commercial enzyme-linked immunosorbent
      assay (ELISA) test. Pregnancy was determined either postmortem (n = 5) or by
      visualization of parturition (n = 33). The other sera were controls from known
      nonpregnant females (n = 71). The following values were obtained: sensitivity =
      100.0%, specificity = 95.8%. Using a commercial ELISA for the detection of PAGs
      appears to be a rapid, inexpensive, and accurate test for pregnancy diagnosis in
      the endangered Barbary sheep. The number of offspring cannot be determined with
      this method.

PMID- 28749286
TI  - DETECTION OF AEROSOLIZED BACTERIA IN EXPIRED AIR SAMPLES FROM ASIAN ELEPHANTS
      (ELEPHAS MAXIMUS).
AB  - Elephant-mediated transmission of tuberculosis is assumed to be similar to human
      models, which state close and prolonged contact with an infected individual is
      required for transmission. Although considered a risk factor for infection,
      several case studies have reported that close contact with an elephant is not
      always necessary for transmission, and the role of aerosolized bacteria remains
      unclear. To investigate aerosol-mediated transmission of pathogenic bacteria from
      elephants, a method for the detection of aerosols using an adapted sampling
      system was developed. A commensal bacterium was isolated from the upper
      respiratory tract of elephants ( Elephas maximus ) and was used as a proxy
      organism to detect aerosolized droplets in the sampling system. It was found that
      elephants are capable of producing aerosolized bacterial particles of a size
      small enough to remain airborne for prolonged periods and penetrate the lower
      regions of the human respiratory tract.

PMID- 28749287
TI  - HEMATOLOGIC AND PLASMA BIOCHEMICAL VALUES OF CINEREOUS VULTURE (AEGYPIUS
      MONACHUS).
AB  - The aim of this study was to establish hematologic and plasma biochemical
      reference intervals for clinically healthy cinereous vultures ( Aegypius monachus
      ) in a rehabilitation setting before release. Animals used in this study were
      cinereous vultures hospitalized in a wildlife center located in the province of
      Gyeongsangnam-do, the Republic of Korea. Blood samples were collected from 31
      cinereous vultures before their release between 2011 and 2014 at the Gyeongnam
      Wildlife Center. Complete blood count and plasma biochemical analyses were
      performed within 2 hr of the blood sampling. Reference intervals were calculated
      from the 10th to the 90th percentile, together with the mean, SD, and lowest and
      highest observed values. The results of this study may be useful in evaluating
      the physical condition and clinical monitoring of cinereous vultures in captivity
      before release and contribute to the determination of reference ranges for
      healthy cinereous vultures.

PMID- 28749288
TI  - BLOOD PRODUCT TRANSFUSIONS IN GREAT APES: A RETROSPECTIVE REVIEW OF 12 CASES.
AB  - Although the administration of blood and blood products can be lifesaving,
      transfusions in exotic species are less common because of the lack of knowledge
      of a species' blood groups, the availability of species-specific donors, and
      possible adverse effects. Recently, blood groups were elucidated in great apes;
      however, few reports have been published regarding actual transfusion situations
      in these species. This information is critical because poorly executed
      transfusions can compromise already weakened patients or result in the death of
      the recipient. In 2014, a retrospective survey of U.S. zoos housing great apes
      received 45 of 67 responses; from which, 12 transfusion cases in great apes were
      identified, including Sumatran orangutans ( Pongo pygmaeus sumatraensis, n = 4),
      chimpanzee ( Pan troglodytes , n = 1), and western lowland gorillas ( Gorilla
      gorilla gorilla, n = 7). These animals, ranging from birth to 31 yr, received
      intravenous transfusions of whole blood, packed red blood cells, or human
      albumin. Overall, animals that received transfusions for anemia because of
      chronic illness or blood loss survived, but those individuals with concurrent
      life-threatening issues did not survive. No adverse reactions related to the
      transfusion occurred, except in two orangutans given human albumin.

PMID- 28749289
TI  - CLINICAL DISEASE ASSOCIATED WITH ANAPLASMA PHAGOCYTOPHILUM INFECTION IN CAPTIVE
      PRZEWALSKI'S HORSES (EQUUS FERUS PRZEWALSKII).
AB  - Anaplasma phagocytophilum is a tick-borne pathogen of domestic horses and the
      causative agent of equine granulocytic anaplasmosis. This case series describes
      three confirmed cases of clinical anaplasmosis, and a fourth case of presumptive
      anaplasmosis in Przewalski's horses ( Equus ferus przewalskii) housed at the
      Smithsonian Conservation Biology Institute from 2008 to 2014. Clinical signs
      varied among individuals with affected horses exhibiting lethargy, weakness,
      pyrexia, hypophagia, reluctance to move, or ataxia. Anaplasmosis cases were
      confirmed with a combination of identification of neutrophilic inclusions
      (morulae) on peripheral blood smear, positive polymerase chain reaction (PCR)
      testing of whole blood, or convalescent titers. All animals recovered after
      antimicrobial therapy with oxytetracycline. Diagnosis should be made by a
      combination of clinical signs plus identification of morulae or positive A.
      phagocytophilum PCR. Treatment is curative using oxytetracyline intramuscularly
      or intravenously followed by daily therapy with oxytetracyline or minocycline for
      14-30 days. The authors recommend that A. phagocytophilum infection be included
      on any differential list for Przewalski's horses presenting with fever or ataxia
      within or near an enzootic area.

PMID- 28749290
TI  - GRANULOMATOUS ENCEPHALOMYELITIS IN A FALSE GHARIAL (TOMISTOMA SCHLEGELII)
      ASSOCIATED WITH A NOVEL CHLAMYDIA SPECIES.
AB  - A 5-yr-old, captive, hatched, female false gharial (Tomistoma schlegelii)
      presented with a 1-mo history of cervical spinal curvature. Antemortem
      diagnostics, including blood work, electromyography, muscle biopsies, and
      advanced imaging tests, were either within reference ranges or did not identify
      any specific etiology. Necropsy revealed extensive, marked, chronic granulomatous
      encephalomyelitis along with neuronal necrosis, rarefaction, gliosis, and
      astrocytosis of the white and gray matter of the cerebrum, cerebellum, brainstem,
      and spinal cord. Pan-chlamydiae polymerase chain reaction protocols for the 16S
      ribosomal RNA and ompA genes were performed on samples of spinal cord and brain,
      and both resulted in amplicons. Sequencing of the products revealed that they
      were positive for a novel Chlamydia species. Infections by members of the phylum
      Chlamydiae have been reported in a diverse range of vertebrate hosts, including
      crocodilians. Chlamydia spp. infections are likely underdiagnosed because of a
      paucity of diagnostic techniques specific for detection. This is the first case
      report of a novel Chlamydia species associated with severe granulomatous
      encephalomyelitis in a false gharial.

PMID- 28749291
TI  - DETECTION OF INTRANUCLEAR COCCIDIOSIS IN TORTOISES IN EUROPE AND CHINA.
AB  - Intranuclear coccidiosis of tortoises (TINC) has been described in association
      with systemic disease in various species of tortoises. TINC has been detected in
      numerous tortoises from the United States, but there are only a few reports from
      tropical tortoises in Germany and no reports from Asia. Using a real-time
      polymerase chain reaction assay, samples from 1,011 tortoises were screened for
      the presence of TINC. Samples originated from animals kept in captivity in Europe
      and in China. Coccidia were detected in a total of 27 chelonians (2.7%),
      including the first description of TINC in a marginated tortoise ( Testudo
      marginata ), Hermann's tortoise ( Testudo hermanni ), African spurred tortoise
      (Centrochelys sulcata), and yellow-footed tortoise (Chelonoidis denticulatus).
      The highest percentage of positive animals was found in radiated tortoises (
      Astrochelys radiata ). Although the percentage of positive animals was relatively
      low, this study demonstrates the global distribution of TINC in captive
      chelonians as well as expanding the known host range for these pathogens.

PMID- 28749292
TI  - MOLECULAR DETECTION OF INFECTIOUS PATHOGENS OF THE UPPER RESPIRATORY TRACT IN
      CAPTIVE NONDOMESTIC FELIDS.
AB  - Upper respiratory tract disease is a complex infectious disease process with
      multiple pathogens involved. Identification of infectious agents in wild animals
      is of great importance for wildlife conservation. The aim of this study was to
      evaluate the molecular detection of feline herpesvirus type 1, feline calicivirus
      (FCV), Bordetella bronchiseptica , Chlamydophila felis , and Mycoplasma felis
      using ocular and nasal swabs in three species of captive nondomestic felids.
      Mycoplasma felis was detected in two ocular samples of Puma concolor and in one
      nasal sample of one Panthera onca . FCV was detected in association with M. felis
      in one P. concolor . The other pathogens tested were not detected. To the
      authors' knowledge, this is the first report of M. felis in nondomestic felids
      from Brazil.

PMID- 28749293
TI  - DIAGNOSIS AND SUCCESSFUL TREATMENT OF A POTENTIALLY ZOONOTIC DERMATOPHYTOSIS
      CAUSED BY MICROSPORUM GYPSEUM IN A ZOO-HOUSED NORTH AMERICAN PORCUPINE (ERETHIZON
      DORSATUM).
AB  - A female North American porcupine ( Erethizon dorsatum ) was evaluated for a
      unilateral pedal crusting and alopecic dermatopathy. Fungal culture and
      histopathology testing revealed Microsporum gypseum dermatophytosis. Treatment
      with topical miconazole was initiated and then discontinued after 9 days and
      changed to oral terbinafine. Twenty-eight days after initial examination,
      clinical signs were improving, and fungal cultures of the front foot, muzzle, and
      noninfected area along the dorsum were negative for M. gypseum. Visual exams were
      conducted on a regular basis. Eighty-three days after initial evaluation,
      clinical signs had completely resolved and repeat fungal cultures were negative.
      One of the animal's keepers was suspected to have acquired a dermal fungal
      infection 3 days after contact with this porcupine, and lesions had resolved
      after treatment with topical ketoconazole. To the authors' knowledge, this is the
      first report of M. gypseum diagnosed and treated in a captive North American
      porcupine. Veterinary staff and zookeepers should be aware of this potentially
      zoonotic infection.

PMID- 28749294
TI  - OSTEOSARCOMA IN AFRICAN HEDGEHOGS (ATELERIX ALBIVENTRIS): FIVE CASES.
AB  - Osteosarcomas are unusual neoplasms in African hedgehogs ( Atelerix albiventris )
      and have been reported in extraskeletal and skeletal locations, including
      mandible, ribs, and vertebra. Five hedgehogs with osteosarcoma submitted to the
      Pathology Department at Facultad de Medicina Veterinaria y Zootecnia, National
      Autonomous University of Mexico are reported. In two cases, the neoplasm arose
      from the skull; one case arose from the ribs with associated compression of the
      thoracic and abdominal cavity, and another case involved the vertebrae. In the
      last case, the neoplasm arose from the scapula. Histologic lesions were similar
      in all cases and consisted of well-demarcated nodules in which neoplastic cells
      were arranged in sheets of polyhedral to spindle-shaped cells with interspersed
      areas of necrosis. Numerous trabeculae of osteoid were present throughout the
      tumors. No metastases were detected. The predominant histologic pattern was
      osteoblastic, but a telangiectatic-like pattern was observed in the vertebral
      osteosarcoma. Electron microscopy was performed in two cases, and malignant
      osteoblasts had features consistent with descriptions in other species, including
      deposits of hydroxyapatite in osteoid. According to these cases and previously
      published data, axial osteosarcomas are more frequent in contrast to appendicular
      osteosarcomas in African hedgehogs, and metastases are rare.

PMID- 28749295
TI  - SERIAL ULTRASOUND TO ESTIMATE FETAL GROWTH CURVES IN SOUTHERN TAMANDUA (TAMANDUA
      TETRADACTYLA).
AB  - From 2012 to 2015, 16 pregnancies were monitored by ultrasonography in nine
      tamanduas ( Tamandua tetradactyla ) housed in three zoological facilities.
      Sonographic measurements were recorded to establish fetal growth curves using
      thoracic and skull landmarks described for giant anteaters ( Myrmecophaga
      tridactyla ). All pregnancies resulted in the uncomplicated delivery of healthy
      offspring, thus gestational development was considered normal. These data may be
      used as a reference for normal fetal development with potential for estimating
      parturition date in the absence of breeding data.

PMID- 28749296
TI  - BRIDGING GAPS BETWEEN ZOO AND WILDLIFE MEDICINE: ESTABLISHING REFERENCE INTERVALS
      FOR FREE-RANGING AFRICAN LIONS (PANTHERA LEO).
AB  - The International Species Information System has set forth an extensive database
      of reference intervals for zoologic species, allowing veterinarians and game park
      officials to distinguish normal health parameters from underlying disease
      processes in captive wildlife. However, several recent studies comparing
      reference values from captive and free-ranging animals have found significant
      variation between populations, necessitating the development of separate
      reference intervals in free-ranging wildlife to aid in the interpretation of
      health data. Thus, this study characterizes reference intervals for six
      biochemical analytes, eleven hematologic or immune parameters, and three hormones
      using samples from 219 free-ranging African lions ( Panthera leo ) captured in
      Kruger National Park, South Africa. Using the original sample population,
      exclusion criteria based on physical examination were applied to yield a final
      reference population of 52 clinically normal lions. Reference intervals were then
      generated via 90% confidence intervals on log-transformed data using parametric
      bootstrapping techniques. In addition to the generation of reference intervals,
      linear mixed-effect models and generalized linear mixed-effect models were used
      to model associations of each focal parameter with the following independent
      variables: age, sex, and body condition score. Age and sex were statistically
      significant drivers for changes in hepatic enzymes, renal values, hematologic
      parameters, and leptin, a hormone related to body fat stores. Body condition was
      positively correlated with changes in monocyte counts. Given the large variation
      in reference values taken from captive versus free-ranging lions, it is our hope
      that this study will serve as a baseline for future clinical evaluations and
      biomedical research targeting free-ranging African lions.

PMID- 28749297
TI  - EBSTEIN ANOMALY IN THE TSUSHIMA LEOPARD CAT (PRIONAILURUS BENGALENSIS
      EUPTILURUS).
AB  - Ebstein anomaly is a rare congenital heart disease that has been described in
      domestic dogs, a meerkat, a pygmy goat, and a lion. An 11-mo-old Tsushima leopard
      cat presented to Osaka Prefecture University Veterinary Hospital for diagnosis
      and treatment of right-sided congestive heart failure. Echocardiography showed a
      dilated right atrium and ventricle with an enlarged tricuspid valve annulus and
      apical displacement of the tricuspid valve leaflets. The cat was diagnosed with
      Ebstein anomaly. To the best of our knowledge, this is the first report of this
      type of congenital heart disease in a Tsushima leopard cat.

PMID- 28749298
TI  - SUCCESSFUL MANAGEMENT OF CECAL PERFORATION AND FOCAL PERITONITIS IN A GORILLA
      (GORILLA GORILLA GORILLA).
AB  - An 18-yr-old female Western lowland gorilla ( Gorilla gorilla gorilla) presented
      with acute-onset severe lethargy, bloody vaginal discharge, decreased appetite,
      and an abnormal posture. The gorilla was diagnosed with a ruptured cecal blind
      sac with severe adhesions to the right ovary. A typhlectomy and unilateral
      ovariectomy were performed. Histologic examination identified a severe transmural
      circumferential typhlitis with rupture and adhesions to the infundibulum and
      chronic typhlitis. Postoperative management included antibiotics, analgesics,
      short-term dietary modifications, and probiotics for suspect oral candidiasis.
      The gorilla made a full clinical recovery and was pregnant within 1 yr of
      surgery. To the authors' knowledge, this is the first case of successful
      management of typhlitis in a gorilla. Typhlitis and intestinal rupture should be
      considered as a differential diagnosis for acute onset severe abdominal pain in
      gorillas.

PMID- 28749299
TI  - AAZV PUBLICATIONS AVAILABLE.

PMID- 28749301
TI  - PILOT STUDY: PHARMACOKINETICS OF ORAL AND TOPICAL MOXIDECTIN IN THE RETICULATED
      GIRAFFE (GIRAFFA CAMELOPARDALIS).
AB  - The objective of this study was to obtain an estimate of the pharmacokinetic
      parameters of moxidectin administered at a dosage of 1 mg/kg orally and topically
      to healthy adult giraffe ( Giraffa camelopardalis ). The maximum plasma
      concentration (CMAX) of moxidectin after oral and topical administration was 69.2
      +/- 4.6 and 18.6 +/- 16.1 ng/ml (P = 0.045), respectively. The areas under the
      plasma curve (AUC), a measure of total drug exposure, was 532.0 +/- 232.3 and
      209.1 +/- 180.0 day*ng/ml (P = 0.308) for the oral and topical administrations,
      respectively. These data suggest moxidectin achieves higher peak plasma
      concentrations following oral administration compared with topical (transdermal)
      administration using the cattle pour-on formulation. Additionally, the percent
      coefficient of variation, a measure of variability, was smaller for the oral
      formulation (CMAX %CV = 7%; AUC %CV = 44%) compared with the topical formulation
      (CMAX %CV = 86%; AUC %CV = 86%). The smaller variability suggests that oral
      administration of moxidectin produces more predictable and less variable drug
      absorption than topical administration in giraffe and is the preferred route of
      administration.

PMID- 28749302
TI  - SQUAMOUS CELL CARCINOMA IN TWO SNOW LEOPARDS (UNCIA UNCIA) WITH UNUSUAL AURICULAR
      PRESENTATION.
AB  - Squamous cell carcinoma (SCC) is well documented in snow leopards ( Uncia uncia )
      and most common locations are oral, facial, or pedal. These two cases illustrate
      an unusual auricular presentation, which is more often reported in white domestic
      cats. The animals were aged and presented clinical signs of otitis such as head
      shaking and ear scratching. Clinical examinations showed auricular canal masses
      with chronic purulent otitis. In both cases, clinical deterioration led to
      euthanasia and histology of the ear canal was consistent with SCC and showed
      numerous vascular emboli. These cases illustrate an unreported aggressive
      localization for SCC in snow leopards, which should be included in the
      differential diagnosis of otitis in this species. Auricular SCC may be
      underdiagnosed as the ear canal is infrequently sampled for histopathology. This
      auricular localization should be considered when metastases are found upon
      necropsy without internal primary tumor.

PMID- 28749303
TI  - GASTRIC DILATATION VOLVULUS IN ADULT MANED WOLVES (CHRYSOCYON BRACHYURUS).
AB  - Gastric dilatation volvulus (GDV) was identified in six adult maned wolves (
      Chrysocyon brachyurus ) housed at the Smithsonian Conservation Biology Institute
      in Front Royal, Virginia, and the Dickerson Park Zoo in Springfield, Missouri.
      Four individuals were found dead in their enclosures, and GDV was diagnosed
      postmortem based on radiographic and necropsy findings. Two individuals were
      diagnosed with GDV antemortem, with one wolf surviving following surgical
      intervention and supportive management. A concurrent splenic torsion was
      identified in three of six cases. Although GDV has been well documented in
      domestic dogs and is known to occur in maned wolves, objective, detailed case
      descriptions have been limited in this species. This report represents the first
      description of a surviving case of GDV in the maned wolf. Thorough species
      specific documentation of any acutely fatal condition, such as GDV, is imperative
      for proper case recognition and medical management, with profound implications
      for species recovery efforts.

PMID- 28749304
TI  - INVESTIGATION OF ENROFLOXACIN-ASSOCIATED RETINAL TOXICITY IN NONDOMESTIC FELIDS.
AB  - Enrofloxacin is known to cause retinal toxicity in domestic cats. The hallmark
      lesion of enrofloxacin-associated retinal toxicity in domestic cats is thinning
      of the outer nuclear layer of the retina. Enrofloxacin is commonly used to treat
      bacterial infections in nondomestic felids because of its action against a wide
      spectrum of bacteria and the ability for it to be given orally. No previous
      studies have investigated the potential retinal toxicity of enrofloxacin in
      nondomestic felids. This retrospective study evaluated 81 eyes from 14 lions (
      Panthera leo ) and 33 tigers ( Panthera tigris ) that had been enucleated or
      collected postmortem. The thickness of the outer nuclear retina was assessed in
      two separate sites in each eye by counting the rows of nuclei and by using
      digital image analysis software to determine the area of the nuclei at each site.
      Medical records were reviewed to determine the enrofloxacin dose for each cat.
      Cats that had not received enrofloxacin (n = 11) were compared with treated
      animals (n = 36). The outer nuclear layer thickness or area in treated versus
      untreated cats was not significantly different. Additionally, no clinical
      blindness was reported in any of the cats. This study showed no evidence of
      enrofloxacin-associated thinning of the outer nuclear layer in the lions and
      tigers evaluated, suggesting that enrofloxacin can be used safely in these
      animals.

PMID- 28749305
TI  - THE PHARMACOKINETICS OF TOPICAL ITRACONAZOLE IN PANAMANIAN GOLDEN FROGS (ATELOPUS
      ZETEKI).
AB  - Chytridiomycosis is caused by the fungus Batrachochytrium dendrobatidis and is
      one of the primary causes of the global decline in amphibian populations and
      specifically of the Panamanian golden frog ( Atelopus zeteki ). Itraconazole has
      been demonstrated to be an effective treatment for chytridiomycosis by inhibiting
      cytochrome P450, a major enzyme important for the structure of B. dendrobatidis
      zoospores' plasma membranes. However, anecdotal reports of toxicity in this and
      other amphibian species have been reported at the 0.01% concentration. This study
      is the first to determine pharmacokinetics of 0.01% and 0.001% itraconazole in
      the Panamanian golden frog. Frogs were bathed 10 min, euthanized, and skin,
      liver, and heart were collected at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, and 36 hr.
      Itraconazole concentrations were measured using high performance liquid
      chromatography, and the minimum inhibitory concentration (MIC) of itraconazole
      (0.032 MUg/ml) for B. dendrobatidis was used to determine whether therapeutic
      concentrations were attained. Itraconazole was detected in all tissues at both
      concentrations, indicating systemic absorption. At the 0.01% itraconazole bath,
      itraconazole concentrations in all tissues exceeded the MIC at all time points,
      and the lack of decline until the end of the study at 36 hr precluded determining
      a disappearance half-life. With the 0.001% bath, itraconazole exceeded the MIC
      and declined with a disappearance half-life that markedly varied (14.1-1,244
      min). This study augments the growing literature base on chytridiomycosis and
      seeks to aid in further experimental attempts to find the most-optimal treatment
      protocol for this disease.

PMID- 28749306
TI  - SUCCESSFUL TREATMENT OF DIGITAL OSTEITIS BY INTRAVENOUS REGIONAL PERFUSION OF
      CEFTIOFUR IN AN AFRICAN ELEPHANT (LOXODONTA AFRICANA).
AB  - A 41-yr-old African elephant ( Loxodonta africana ) presented with a swollen
      third digit of the left forelimb and a 2-cm hole in the pad. Corrective trimming,
      topical treatments, and an oral antibiotic resulted in apparent resolution;
      however, it reoccurred after 4 mo. Radiographs suggested bone lysis in the third
      phalanx, with the primary differential diagnosis being septic osteitis. Flushing
      with metronidazole solution and intravenous regional perfusion (IVRP) of the foot
      were commenced. A tourniquet was applied just above the carpus, an interdigital
      vein was identified by ultrasound, and into this vein 2 g (20 ml) of ceftiofur
      sodium solution, followed by 60 ml of heparinized saline, was administered. The
      foot was kept raised for 25 min and then the tourniquet was removed. IVRP was
      repeated every other day for 70 treatments over 6 mo. Healing occurred, which was
      confirmed radiographically. IVRP offers an excellent treatment modality in a well
      trained elephant.

PMID- 28749307
TI  - RECURRENT EAR MITE (OTODECTES CYNOTIS) INFESTATION IN THREE RELATED GROUPS OF
      PATAGONIAN CAVIES (DOLICHOTIS PATAGONUM).
AB  - :  Two of three groups of Patagonian cavies ( Dolichotis patagonum ) contracted
      Otodectes cynotis infestations after exposure to mite-infested feral cats.
      Otodectes cynotis infestations were initially identified in 9 of 10 cavies in
      group 1. Multiple feral cats with O. cynotis infestations were observed in the
      vicinity of the Patagonian cavies and were subsequently removed. The Patagonian
      cavies were initially treated with ivermectin (0.4 mg/kg s.q.) every 2 wk, but
      ivermectin was discontinued after the third treatment due to injury to one of the
      Patagonian cavies during capture. Sixteen months after initial treatment,
      clinical signs of scratching the pinnae, hemorrhagic lesions on the ear margins,
      head shaking, and O. cynotis mites in the auricular canal were again noted in all
      Patagonian cavies in group 1. Repeated administration of ivermectin (0.4 mg/kg
      s.q. every 2 wk for three treatments) failed to eliminate the mites in two of the
      Patagonian cavies. Selamectin administered (20 mg/kg, topically between the
      shoulder blades) to all Patagonian cavies eliminated the mite infestation after a
      single application. The Patagonian cavies remained O. cynotis mite free for 2 yr,
      until males (group 2) and females (group 3) were separated for population
      control. Three months after separation, 8 of the 12 females in group 3 again were
      infestated with O. cynotis mites. Feral cats with O. cynotis infestations were
      again noted in the vicinity of group 3. A single dose of selamectin applied
      topically eliminated all mites in all treated Patagonian cavies. Group 2 was not
      exposed to feral cats and remained mite free.

PMID- 28749308
TI  - EVALUATION OF THE EFFECTS OF STERNAL VERSUS LATERAL RECUMBENCY ON TRENDS OF
      SELECTED PHYSIOLOGIC PARAMETERS DURING ISOFLURANE ANESTHESIA IN ZOO-HOUSED BLACK
      TAILED PRAIRIE DOGS (CYNOMYS LUDOVICIANUS).
AB  - Isoflurane gas anesthesia is often used for immobilization of prairie dogs in
      field studies, laboratory research, and veterinary clinical purposes. The goals
      of this prospective study were to evaluate the effects of sternal versus right
      lateral recumbency on trends of selected physiologic parameters during isoflurane
      anesthesia in black-tailed prairie dogs ( Cynomys ludovicianus ). Fourteen adult,
      zoo-housed black-tailed prairie dogs were tested during the study. Animals were
      anesthetized using isoflurane and randomly placed in either sternal or right
      lateral recumbency to evaluate changes in trends of physiologic parameters,
      measured selectively every 30 min throughout a 60-min anesthesia period. Results
      were analyzed using linear mixed modeling. Right lateral recumbency resulted in a
      decrease in anion gap of about 4.6 mEq/L (95% confidence interval [95% CI]: 3.1
      6.0, P < 0.001), whereas sternal recumbency resulted in a lower decrease of 2.1
      mEq/L (95% CI: 0.7-3.6, P = 0.02). However, the absolute values at the beginning
      and at the end of the anesthesia time were not significantly different between
      the right lateral and sternal recumbency (all P > 0.57). Body position did not
      have any effect on any other variables, and most of the observed physiologic
      changes were due to the duration of anesthesia. Our results indicate no
      significant effect on trends of selected physiologic parameters between sternal
      recumbency and right lateral recumbency during 1 hr of isoflurane anesthesia in
      black-tailed prairie dogs.

PMID- 28749309
TI  - Correction to: Stracquadanio and Ciotta, Low birth-weight is a PCOS risk factor
      for Southern-Italian women.

PMID- 28749310
TI  - Reconstitution of the peripheral immune repertoire following withdrawal of
      fingolimod.

PMID- 28749311
TI  - Reconstitution of the peripheral immune repertoire following withdrawal of
      fingolimod.
AB  - BACKGROUND: Following fingolimod cessation, immune reconstitution or lack thereof
      may have consequences for disease rebound or safety of commencing alternative
      therapies. OBJECTIVE: To examine the degree and profile of peripheral blood
      lymphocyte reconstitution following fingolimod withdrawal. METHODS: Total
      lymphocyte counts (TLC) and CD4+/CD8+ T-cell counts were measured in 18 multiple
      sclerosis (MS) patients pre-treatment, on fingolimod, and up to 8-9 months post
      cessation. T-cell subsets were analyzed using flow cytometry. RESULTS: At 2-week
      post-fingolimod cessation, TLC reconstitution was variable and not correlated
      with age, treatment duration, pre-, or on-treatment TLC. Despite normalization of
      TLC and CD4+:CD8+ ratios over months, naive subsets remained lower and effector
      memory subsets higher in frequency compared with pre-treatment. Drug-induced
      increases in ratios of regulatory to pathogenic Th17-containing central memory
      populations appeared to rapidly return to baseline. CONCLUSION: Early peripheral
      lymphocyte reconstitution after fingolimod withdrawal remains partial and
      heterogeneous. Relative frequencies of circulating naive and memory T-cell
      subsets may not recover for many months, even when clinical laboratory tests have
      normalized. Analyzing specific components of the peripheral immune repertoire
      helps define the overall immune status of patients. To be determined is whether
      assessment of such immune measures will have implications for the timing and
      safety of commencing alternative therapies.

PMID- 28749312
TI  - Do cultures vary in self-enhancement? ERP, behavioral, and self-report evidence.
AB  - Psychologists have long debated whether self-enhancement is universal or varies
      across cultures. Extant studies using explicit and implicit measures have
      provided mixed results. In this study (N = 93; 35 European American, 58 Chinese:
      28 tested in English, 30 tested in Mandarin), we measured self-enhancement
      covertly using an ERP paradigm. Self-enhancement was also assessed via self
      report and reaction-time based measures. Americans showed strong evidence of self
      enhancement across all measures, whereas this effect was absent or weaker among
      Chinese, who instead showed an other-enhancing bias across measures. Language did
      not affect self-enhancement tendencies among Chinese participants, with the
      exception of one self-report measure. Nor did the two cultural groups differ in
      enhancement for a close other. This is the first study to directly compare self
      enhancement across cultural groups using ERPs and provides evidence that positive
      self-regard does indeed vary by culture.

PMID- 28749313
TI  - In this issue: Innovation in design and implementation in health informatics.
AB  - NA.

PMID- 28749314
TI  - Designing Health Information Technology Tools to Prevent Gaps in Public Health
      Insurance.
AB  - BACKGROUND: Changes in health insurance policies have increased coverage
      opportunities, but enrollees are required to annually reapply for benefits which,
      if not managed appropriately, can lead to insurance gaps. Electronic health
      records (EHRs) can automate processes for assisting patients with health
      insurance enrollment and re-enrollment. OBJECTIVE: We describe community health
      centers' (CHC) workflow, documentation, and tracking needs for assisting families
      with insurance application processes, and the health information technology (IT)
      tool components that were developed to meet those needs. METHOD: We conducted a
      qualitative study using semi-structured interviews and observation of clinic
      operations and insurance application assistance processes. Data were analyzed
      using a grounded theory approach. We diagramed workflows and shared information
      with a team of developers who built the EHR-based tools. RESULTS: Four steps to
      the insurance assistance workflow were common among CHCs: 1) Identifying patients
      for public health insurance application assistance; 2) Completing and submitting
      the public health insurance application when clinic staff met with patients to
      collect requisite information and helped them apply for benefits; 3) Tracking
      public health insurance approval to monitor for decisions; and 4) assisting with
      annual health insurance reapplication. We developed EHR-based tools to support
      clinical staff with each of these steps. CONCLUSION: CHCs are uniquely positioned
      to help patients and families with public health insurance applications. CHCs
      have invested in staff to assist patients with insurance applications and help
      prevent coverage gaps. To best assist patients and to foster efficiency, EHR
      based insurance tools need comprehensive, timely, and accurate health insurance
      information.

PMID- 28749315
TI  - Connecting Medical Records: An Evaluation of Benefits and Challenges for Primary
      Care Practices.
AB  - BACKGROUND: Implementation of systems to support health information sharing has
      lagged other areas of healthcare IT, yet offers a strong possibility for benefit.
      Clinical acceptance is a key limiting factor in health IT adoption. OBJECTIVES:
      To assess the benefits and challenges experienced by clinicians using a custom
      developed health information exchange system, and to show how perceptions of
      benefits and challenges influence perceptions of productivity and care-related
      outcomes. METHODS: We used a mixed methods design with two phases. First, we
      conducted interviews with stakeholders who were familiar with the health
      information exchange system to inform the development of a measure of benefits
      and challenges of the use of this system. Second, using this measure we conducted
      a survey of current and former users of the health information exchange system
      using a modified Dillman method. RESULTS: 105 current and former users completed
      the survey. The results showed information quality, ease of completing tasks and
      clinical process improvement as key benefits that reduced workload and improved
      patient care.  Challenges related to system reliability, quality of reports and
      service quality increased workload and decreased impact on care, though the
      effect of the challenges was smaller than that of the benefits. CONCLUSIONS: 
      Even very limited health information exchange capabilities can improve outcomes
      for primary care users.  Improving perceptions of benefits may be even more
      important the removing challenges to use, though it is likely that a threshold of
      quality must be achieved for this to be true.

PMID- 28749316
TI  - "It's like texting at the dinner table": A qualitative analysis of the impact of
      electronic health records on patient-physician interaction in hospitals.
AB  - : nBACKGROUND: Electronic health records (EHRs) may reduce medical errors and
      improve care, but can complicate clinical encounters. OBJECTIVE: To describe
      hospital-based physicians' perceptions of the impact of EHRs on patient-physician
      interactions and contrast these findings against office-based physicians'
      perceptionsMethods: We performed a qualitative analysis of comments submitted in
      response to the 2014 Rhode Island Health Information Technology Survey. Office-
      and hospital-based physicians licensed in Rhode Island, in active practice, and
      located in Rhode Island or neighboring states completed the survey about their
      Electronic Health Record use. RESULTS: The survey's response rate was 68.3% and
      2,236 (87.1%) respondents had EHRs. Among survey respondents, 27.3% of hospital
      based and 37.8% of office-based physicians with EHRs responded to the question
      about patient interaction. Five main themes emerged for hospital-based
      physicians, with respondents generally perceiving EHRs as negatively altering
      patient interactions. We noted the same five themes among office-based
      physicians, but the rank-order of the top two responses differed by setting:
      hospital-based physicians commented most frequently that they spend less time
      with patients because they have to spend more time on computers; office-based
      physicians commented most frequently on EHRs worsening the quality of their
      interactions and relationships with patients. CONCLUSION: In our analysis of a
      large sample of physicians, hospital-based physicians generally perceived EHRs as
      negatively altering patient interactions, although they emphasized different
      reasons than their office-based counterparts. These findings add to the prior
      literature, which focuses on outpatient physicians, and can shape interventions
      to improve how EHRs are used in inpatient settings.

PMID- 28749317
TI  - Understanding the use of geographical information systems (GIS) in health
      informatics research: A review.
AB  - BACKGROUND: The purpose of this literature review is to understand geographical
      information systems (GIS) and how they can be applied to public health
      informatics, medical informatics, and epidemiology. METHOD: Relevant papers that
      reflected the use of geographical information systems (GIS) in health research
      were identified from four academic databases: Academic Search Complete, BioMed
      Central, PubMed Central, and Scholars Portal, as well as Google Scholar. The
      search strategy used was to identify articles with "geographic information
      systems", "GIS", "public health", "medical informatics", "epidemiology", and
      "health geography" as main subject headings or text words in titles and
      abstracts. Papers published between 1997 and 2014 were considered and a total of
      39 articles were included to inform the authors on the use of GIS technologies in
      health informatics research. RESULTS: The main applications of GIS in health
      informatics and epidemiology include disease surveillance, health risk analysis,
      health access and planning, and community health profiling. GIS technologies can
      significantly improve quality and efficiency in health research as substantial
      connections can be made between a population's health and their geographical
      location. CONCLUSIONS: Gains in health informatics can be made when GIS are
      applied through research, however, improvements need to occur in the quantity and
      quality of data input for these systems to ensure better geographical health maps
      are used so that proper conclusions between public health and environmental
      factors may be made.

PMID- 28749318
TI  - Probabilistic linkage to enhance deterministic algorithms and reduce data linkage
      errors in hospital administrative data.
AB  - :  BACKGROUND: The pseudonymisation algorithm used to link together episodes of
      care belonging to the same patients in England (HESID) has never undergone any
      formal evaluation, to determine the extent of data linkage error. OBJECTIVE: To
      quantify improvements in linkage accuracy from adding probabilistic linkage to
      existing deterministic HESID algorithms. METHODS: Inpatient admissions to NHS
      hospitals in England (Hospital Episode Statistics, HES) over 17 years (1998 to
      2015) for a sample of patients (born 13/28th of months in 1992/1998/2005/2012).
      We compared the existing deterministic algorithm with one that included an
      additional probabilistic step, in relation to a reference standard created using
      enhanced probabilistic matching with additional clinical and demographic
      information. Missed and false matches were quantified and the impact on estimates
      of hospital readmission within one year were determined. RESULTS: HESID produced
      a high missed match rate, improving over time (8.6% in 1998 to 0.4% in 2015).
      Missed matches were more common for ethnic minorities, those living in areas of
      high socio-economic deprivation, foreign patients and those with 'no fixed
      abode'. Estimates of the readmission rate were biased for several patient groups
      owing to missed matches, which was reduced for nearly all groups. CONCLUSION:
      Probabilistic linkage of HES reduced missed matches and bias in estimated
      readmission rates, with clear implications for commissioning, service evaluation
      and performance monitoring of hospitals. The existing algorithm should be
      modified to address data linkage error, and a retrospective update of the
      existing data would address existing linkage errors and their implications.

PMID- 28749319
TI  - A survey exploring National Health Service ePrescribing Toolkit use and perceived
      usefulness amongst English hospitals.
AB  - BACKGROUND: There is currently limited guidance for hospitals to implement
      ePrescribing systems. We have developed an ePrescribing Toolkit designed to
      support ongoing implementation, adoption and optimisation of efforts. AIM: To
      investigate the perceived usefulness, reported use and areas for further
      development of the Toolkit by ePrescribing implementers in English hospitals.
      METHODS: Questionnaire-based survey of hospitals that have or are interested in
      implementing ePrescribing systems. RESULTS: We received responses from a total of
      78 individuals representing 49 English NHS Trusts (out of 82 different Trusts who
      were emailed the survey, 60% response rate). The overwhelming majority of
      respondents (92%) were familiar with the ePrescribing Toolkit and 66% reported
      using it to guide their ongoing implementation efforts. The majority of
      ePrescribing Toolkit users (85%) viewed it as a helpful resource. Implementers
      particularly valued the case studies describing lessons learnt from hospitals
      that had already implemented ePrescribing systems. Suggestions for improvement
      included more information in relation to the progress of hospitals implementing
      systems, the names of key contacts in these sites, a list of available systems
      and the contact details of ePrescribing vendors. Respondents also highlighted the
      need for more information on optimisation and specialist prescribing.
      CONCLUSIONS: Interactive elements and learning lessons from early adopter sites
      that had accumulated experiences of implementing systems was viewed as the most
      helpful aspect of the ePrescribing Toolkit. The Toolkit now needs to be further
      developed to facilitate the continuing implementation/optimisation of
      ePrescribing and other health information technology across the NHS.

PMID- 28749320
TI  - Reliability of heart rate mobile apps in young healthy adults: exploratory study
      and research directions.
AB  - BACKGROUND: Recently, a number of smartphone apps appeared that allow for heart
      rate measurements basing on the photoplethysmography principle. In fact, almost
      every smartphone now has a camera with flash that could be used for that. Some
      studies appeared on the reliability of some of those apps, with heterogeneous
      results. OBJECTIVES: The present study aims at adding up evidence in particular
      during physical activity, by comparing 3 apps on two different platforms (IOs and
      Android), on a broad range of heart rates. As gold standard, heart rate has been
      measured with a traditional heart rate monitor. RESULTS: The results suggest that
      heart rate apps might be used for measuring heart rate for fitness aims for many
      individuals, but further research is needed to i) analyse influence of smartphone
      features; ii) identify personal factors hindering measurements, and iii) verify
      reliability on different measurement sites.

PMID- 28749322
TI  - Integration of Slack, a cloud-based team collaboration application, into research
      coordination.
AB  - BACKGROUND: Practitioners of epidemiology require efficient real-time
      communication and shared access to numerous documents in order to effectively
      manage a study. Much of this communication involves study logistics and does not
      require use of Protected Health Information. Slack is a team collaboration app;
      it archives all direct messages and group conversations, hosts documents
      internally, and integrates with the Google Docs application. Slack has both
      desktop and mobile applications, allowing users to communicate in real-time
      without the need to find email addresses or phone numbers or create contact
      lists. METHOD: We piloted the integration of Slack into our research team of one
      faculty member, one research coordinator, and approximately 20 research
      assistants. Statistics describing the app's usage were calculated twelve months
      after its implementation. RESULTS: Results indicating heavy usage by both
      research professionals and assistants are presented. Our Slack group included a
      cumulative 51 users. Between October 2015 and November 2016, approximately 10,600
      messages were sent through Slack; 53% were sent by RA's and 47% were sent by us.
      Of the 106 files stored on Slack, 82% were uploaded by research staff. In a
      January 2016 survey, 100% of RA's agreed or strongly agreed that Slack improved
      communication within the team. CONCLUSION: We demonstrate a model for integration
      of communication technology into academic activities by research teams. Slack is
      easily integrated into the workflow at an urban, academic medical center and is
      adopted by users as a highly effective tool for meeting research teams'
      communication and document management needs.

PMID- 28749321
TI  - Design and implementation of an affordable, public sector electronic medical
      record in rural Nepal.
AB  - INTRODUCTION: Globally, electronic medical records are central to the
      infrastructure of modern healthcare systems. Yet the vast majority of electronic
      medical records have been designed for resource-rich environments and are not
      feasible in settings of poverty. Here we describe the design and implementation
      of an electronic medical record at a public sector district hospital in rural
      Nepal, and its subsequent expansion to an additional public sector
      facility.DevelopmentThe electronic medical record was designed to solve for the
      following elements of public sector healthcare delivery: 1) integration of the
      systems across inpatient, surgical, outpatient, emergency, laboratory, radiology,
      and pharmacy sites of care; 2) effective data extraction for impact evaluation
      and government regulation; 3) optimization for longitudinal care provision and
      patient tracking; and 4) effectiveness for quality improvement initiatives.
      APPLICATION: For these purposes, we adapted Bahmni, a product built with open
      source components for patient tracking, clinical protocols, pharmacy, laboratory,
      imaging, financial management, and supply logistics. In close partnership with
      government officials, we deployed the system in February of 2015, added on
      additional functionality, and iteratively improved the system over the following
      year. This experience enabled us then to deploy the system at an additional
      district-level hospital in a different part of the country in under four weeks.
      We discuss the implementation challenges and the strategies we pursued to build
      an electronic medical record for the public sector in rural Nepal.DiscussionOver
      the course of 18 months, we were able to develop, deploy and iterate upon the
      electronic medical record, and then deploy the refined product at an additional
      facility within only four weeks. Our experience suggests the feasibility of an
      integrated electronic medical record for public sector care delivery even in
      settings of rural poverty.

PMID- 28749323
TI  - Healthcare Utopia or Dystopia?

PMID- 28749324
TI  - Investigation of the Fim1 putative pilus locus of Streptococcus equi subspecies
      equi.
AB  - The Gram-positive bacterium Streptococcus equi subspecies equi (S. equi) is the
      causative agent of strangles, among the most frequently diagnosed infectious
      diseases of horses worldwide. Genome analysis of S. equi strain 4047 (Se4047)
      identified a putative operon, Fim1, with similarity to the pilus loci of other
      Gram-positive bacteria. The Fim1 locus was present in all strains of S. equi and
      its close relative S. equi subspecies zooepidemicus (S. zooepidemicus) that have
      been studied to date. In this study we provide evidence that the putative
      structural pilus proteins, SEQ_0936 and CNE, are produced on the cell surface
      during in vitro growth and in vivo infection. Although the proteins encoded
      within the Fim1 locus are not essential for attachment or biofilm formation, over
      transcription of SEQ_0936 and CNE enhanced attachment to equine tissue in vitro.
      Our data suggest that whilst the Fim1 locus does not produce a polymerized pilus
      structure, the products of the Fim1 locus may fulfil an adhesive function. The
      putative pilus-associated regulator, tetR, which contains a nonsense mutation in
      S. equi, was able to regulate transcription of the Fim1 locus following repair
      and over-transcription, confirming its predicted role in the operon.

PMID- 28749325
TI  - Central and peripheral reservoirs of feline immunodeficiency virus in cats: a
      review.
AB  - Infection with feline immunodeficiency virus (FIV), a lentivirus similar to human
      immunodeficiency virus (HIV), results in lifelong viral persistence and
      progressive immunopathology in the cat. FIV has the ability to infect and produce
      infectious virus in a number of different cell types. FIV provirus can also be
      maintained in a replication-competent but transcriptionally quiescent state,
      facilitating viral persistence over time. Immediately after the initial
      infection, FIV infection quickly disseminates to many anatomical compartments
      within the host including lymphoid organs, gastrointestinal tract and brain.
      Collectively, the anatomic and cellular compartments that harbour FIV provirus
      constitute the viral reservoir and contain foci of both ongoing viral replication
      and transcriptionally restricted virus that may persist over time. The relative
      importance of the different phenotypes observed for infected cells, anatomic
      compartment, replication status and size of the reservoir represent crucial areas
      of investigation for developing effective viral suppression and eradication
      therapies. In this review, we discuss what is currently known about FIV
      reservoirs, and emphasize the utility of the FIV-infected cat as a model for the
      HIV-infected human.

PMID- 28749326
TI  - Pneumococcal neuraminidase activates TGF-beta signalling.
AB  - Neuraminidase A (NanA) is an important virulence factor that is anchored to the
      pneumococcal cell wall and cleaves sialic acid on host substrates. We noted that
      a secreted allele of NanA was over-represented in invasive pneumococcal isolates
      and promoted the development of meningitis when swapped into the genome of non
      meningitis isolates replacing cell wall-anchored NanA. Both forms of recombinant
      NanA directly activated transforming growth factor (TGF)-beta, increased SMAD
      signalling and promoted loss of endothelial tight junction ZO-1. However, in
      assays using whole bacteria, only the cell-bound NanA decreased expression of ZO
      1 and showed NanA dependence of bacterial invasion of endothelial cells. We
      conclude that NanA secretion versus retention on the cell surface does not
      influence neurotropism of clinical isolates. However, we describe a new NanA-TGF
      beta signalling axis that leads to decreased blood-brain barrier integrity and
      enhances bacterial invasion.

PMID- 28749327
TI  - Novel adenoviruses detected in British mustelids, including a unique
      Aviadenovirus in the tissues of pine martens (Martes martes).
AB  - Several adenoviruses are known to cause severe disease in veterinary species.
      Recent evidence suggests that canine adenovirus type 1 (CAV-1) persists in the
      tissues of healthy red foxes (Vulpes vulpes), which may be a source of infection
      for susceptible species. It was hypothesized that mustelids native to the UK,
      including pine martens (Martes martes) and Eurasian otters (Lutra lutra), may
      also be persistently infected with adenoviruses. Based on high-throughput
      sequencing and additional Sanger sequencing, a novel Aviadenovirus, tentatively
      named marten adenovirus type 1 (MAdV-1), was detected in pine marten tissues. The
      detection of an Aviadenovirus in mammalian tissue has not been reported
      previously. Two mastadenoviruses, tentatively designated marten adenovirus type 2
      (MAdV-2) and lutrine adenovirus type 1 (LAdV-1), were also detected in tissues of
      pine martens and Eurasian otters, respectively. Apparently healthy free-ranging
      animals may be infected with uncharacterized adenoviruses with possible
      implications for translocation of wildlife.

PMID- 28749328
TI  - Desulfovibrio DA2_CueO is a novel multicopper oxidase with cuprous, ferrous and
      phenol oxidase activity.
AB  - Desulfovibrio sp. A2 is a novel Gram-negative sulfate-reducing bacterium that was
      isolated from sediments of the Norilsk mining/smelting area in Russia. The
      organism possesses a monocistronic operon encoding a 71 kDa periplasmic
      multicopperoxidase, which we call DA2_CueO. Histidine-tagged DA2_CueO expressed
      from a plasmid in Escherichia coli and purified by Ni-NTA affinity chromatography
      oxidizes Cu+ and Fe2+, and exhibits phenol oxidase activity with 2,2-azino-bis(3
      ethylbenzthiazoline-6-sulphonic acid), 2,3-dihydroxybenzoic acid and 2,6
      dimethoxyphenol as substrates, using O2 as the oxidant. When expressed in an E.
      coli cueO knock-out strain, DA2_CueO exhibits phenol oxidase activity in vivo and
      enhances the copper tolerance of the strain. These findings indicate that the
      DA2_CueO gene of Desulfovibrio sp. A2 encodes a multicopperoxidase with a role in
      metal ion resistance. The enzyme displays some novel structural features, which
      are discussed.

PMID- 28749329
TI  - In vitro efficacy of 16 antimicrobial drugs against a large collection of beta
      lactamase-producing isolates of extraintestinal pathogenic Escherichia coli from
      dogs and cats.
AB  - PURPOSE: The aim of this study was to assess the in vitro efficacy of candidate
      antimicrobials against extended-spectrum beta-lactamase (ESBL)-producing isolates
      of extraintestinal pathogenic Escherichia coli (ExPEC) from companion animals.
      METHODOLOGY: A total of 90 ESBL-producing ExPEC isolates from dogs and cats were
      tested for susceptibility to 16 antimicrobials with the agar dilution method. We
      also identified the ESBLs and AmpC beta-lactamases of these isolates with PCR and
      DNA sequencing.Results/Key findings. All isolates were susceptible to meropenem,
      tebipenem and amikacin (AMK), and various proportions were susceptible to
      latamoxef (LMX, 97.8 %), fosfomycin (FOM, 97.8 %), faropenem (FPM, 96.7 %),
      nitrofurantoin (NFT, 96.7 %), flomoxef (FMX, 93.3 %), piperacillin/tazobactam
      (PTZ, 92.2 %), cefmetazole (CMZ, 91.1 %), chloramphenicol (80.0 %),
      trimethoprim/sulfamethoxazole (64.4 %), amoxicillin/clavulanic acid (63.3 %),
      ceftibuten (60.0 %), tetracycline (52.2 %) and enrofloxacin (10.0 %). A genetic
      analysis showed that 83 of the 90 (92.2 %) isolates were positive for CTX-M-type
      genes: CTX-M-14 (n=26), CTX-M-27 (n=20), CTX-M-55 (n=17), CTX-M-15 (n=12), CTX-M
      2 (n=5), CTX-M-24 (n=2), CTX-M-104 (n=2) and CTX-M-3 (n=1). Eight isolates also
      expressed AmpC beta-lactamase phenotypes. CONCLUSION: This study demonstrates
      that the susceptibility rates to PTZ, CMZ, LMX, AMK, FOM, FPM, NFT and FMX were
      similar to those to carbapenems (>90 %), implying that these drugs are available
      alternatives to carbapenems for the treatment of companion animals infected with
      ExPEC-producing CTX-M-type ESBLs. Further in vivo studies of the effective use of
      these antimicrobials are required.

PMID- 28749330
TI  - In vitro activity of bedaquiline against rapidly growing nontuberculous
      mycobacteria.
AB  - Bedaquiline (BDQ) has been proven to be effective in the treatment of multidrug
      resistant tuberculosis. We hypothesized that BDQ could be a potential agent to
      treat nontuberculous mycobacterial (NTM) infection. The objective of this study
      was to evaluate the in vitro activity of BDQ against rapidly growing mycobacteria
      by assessing the minimal inhibitory concentration (MIC) and minimal bactericidal
      concentration (MBC) against 18 NTM strains. For MIC determination we performed
      the resazurin microtitre assay broth dilution, and for the MBC the c.f.u. was
      determined. BDQ exhibited a strong inhibitory effect against most NTM tested;
      however, for some NTM strains the MBC was significantly higher than the MIC. A
      new finding is that Mycobacterium flavescens has a mutation in the gene atpE
      associated with natural resistance to BDQ. These preliminary promising results
      demonstrate that BDQ could be potentially useful for the treatment of NTM.

PMID- 28749331
TI  - Pertussis surveillance and control: exploring variations and delays in testing,
      laboratory diagnostics and public health service notifications, the Netherlands,
      2010 to 2013.
AB  - Pertussis is most severe among unvaccinated infants (< 1 year of age), and still
      leads to several reported deaths in the Netherlands every year. In order to avoid
      pertussis-related infant morbidity and mortality, pertussis surveillance data are
      used to guide pertussis control measures. However, more insight into the accuracy
      of pertussis surveillance and control, and into the range of healthcare and
      public health-related factors that impede this are needed. We analysed a unique
      combination of data sources from one Dutch region of 1.1 million residents,
      including data from laboratory databases and local public health notifications
      between 2010 and 2013. This large study (n = 12,090 pertussis tests) reveals
      possible misdiagnoses, substantial under-notification (18%, 412/2,301 laboratory
      positive episodes) and a delay between patient symptoms and notification to the
      local public health services (median 34 days, interquartile range (IQR): 27-54).
      It is likely that the misdiagnoses, under-notification and overall delay in
      surveillance data are not unique to this area of the Netherlands, and are
      generalisable to other countries in Europe. In addition to preventive measures
      such as maternal immunisation, based on current findings, we further recommend
      greater adherence to testing guidelines, standardisation of test interpretation
      guidelines, use of automatic notification systems and earlier preventive
      measures.

PMID- 28749332
TI  - Human myiasis caused by the reindeer warble fly, Hypoderma tarandi, case series
      from Norway, 2011 to 2016.
AB  - Hypoderma tarandi causes myiasis in reindeer and caribou (Rangifer tarandus spp.)
      in most northern hemisphere regions where these animals live. We report a series
      of 39 human myiasis cases caused by H. tarandi in Norway from 2011 to 2016.
      Thirty-two were residents of Finnmark, the northernmost county of Norway, one a
      visitor to Finnmark, and six lived in other counties of Norway where reindeer
      live. Clinical manifestations involved migratory dermal swellings of the face and
      head, enlargement of regional lymph nodes, and periorbital oedema, with or
      without eosinophilia. Most cases of human myiasis are seen in tropical and
      subtropical countries, and in tourists returning from such areas. Our findings
      demonstrate that myiasis caused by H. tarandi is more common than previously
      thought. Healthcare professionals in regions where there is a likelihood of human
      infestation with H. tarandi (regions populated by reindeer), or treating
      returning travellers, should be aware of the condition. All clinicians are
      advised to obtain a detailed travel history when assessing patients with
      migratory dermal swellings. On clinical suspicion, ivermectin should be given to
      prevent larval invasion of the eye (ophthalmomyiasis). Since H. tarandi oviposits
      on hair, we suggest wearing a hat as a prevention measure.

PMID- 28749333
TI  - A cluster of invasive meningococcal disease (IMD) caused by Neisseria
      meningitidis serogroup W among university students, France, February to May 2017.
AB  - Between February and May 2017, two cases of invasive meningococcal disease caused
      by a new, rapidly expanding serogroup W meningococci variant were reported among
      students of an international university in Paris. Bacteriological investigations
      showed that isolates shared identical genotypic formula (W:P1.5,2:F1-1:cc11) and
      belonged to the South American/UK lineage. A vaccination campaign was organised
      that aimed at preventing new cases linked to potential persistence of the
      circulation of the bacteria in the students.

PMID- 28749334
TI  - Are pertussis cases reported too late for public health interventions?
      Retrospective analysis of cases in London and South East England, 2010 to 2015.
AB  - In the United Kingdom, pertussis guidance recommends prophylaxis for household
      contacts within 21 days of case symptom onset if the household includes a
      vulnerable contact. The aim of our study was to identify characteristics
      associated with cases reported late for public health action. We reviewed the
      epidemiology of cases reported in London and South East England for the period
      2010 to 2015. We characterised risk factors associated with late reporting of
      cases and described public health actions taken on timely reported cases. From
      2010 to 2015, 9,163 cases of pertussis were reported to health protection teams.
      Only 11% of cases were reported within 21 days of onset, limiting opportunities
      for secondary prevention. Timely reporting was associated with younger age
      groups, pregnancy, being a healthcare worker and being reported by schools or
      hospital clinicians. Late reporting was associated with older age groups and
      general practitioner or laboratory reporting. Delays, such as those due to
      insidious onset and late presentation to healthcare, may be unavoidable; however,
      delay in reporting once a patient presents can be reduced since cases can be
      reported before laboratory confirmation. Thus we recommend working with
      clinicians and laboratories to determine causes and improve early reporting to
      public health.

PMID- 28749335
TI  - Evaluation of a widely used culture-based method for detection of livestock
      associated meticillin-resistant Staphylococcus aureus (MRSA), Denmark and Norway,
      2014 to 2016.
AB  - We evaluated a widely used culture-based method for detection of livestock
      associated meticillin-resistant Staphylococcus aureus (LA-MRSA) in samples
      collected from pigs and the environment inside pig stables in Denmark and Norway.
      Selective enrichment in tryptic soy broth containing cefoxitin and aztreonam led
      to a high ratio of false-negative results (26%; 57/221). On this basis, we
      recommend reconsidering the use of selective enrichment for detection of LA-MRSA
      in animal and environmental samples.

PMID- 28749336
TI  - Ongoing hepatitis A among men who have sex with men (MSM) linked to outbreaks in
      Europe in Tel Aviv area, Israel, December 2016 - June 2017.
AB  - Between December 2016 and June 2017, 19 Hepatitis A virus (HAV)-positive cases,
      17 of which were among men who have sex with men (MSM) were identified in the Tel
      Aviv area. Seven of the 15 sewage samples collected between January and June 2017
      were also HAV-positive. All sequences clustered with two of the three strains
      identified in the current European HAV outbreak. We demonstrate that despite an
      efficient vaccination programme, HAV can still be transmitted to an unvaccinated
      high-risk population.

PMID- 28749337
TI  - International risk of yellow fever spread from the ongoing outbreak in Brazil,
      December 2016 to May 2017.
AB  - States in south-eastern Brazil were recently affected by the largest Yellow Fever
      (YF) outbreak seen in a decade in Latin America. Here we provide a quantitative
      assessment of the risk of travel-related international spread of YF indicating
      that the United States, Argentina, Uruguay, Spain, Italy and Germany may have
      received at least one travel-related YF case capable of seeding local
      transmission. Mitigating the risk of imported YF cases seeding local transmission
      requires heightened surveillance globally.

PMID- 28749338
TI  - Fast two-photon imaging of subcellular voltage dynamics in neuronal tissue with
      genetically encoded indicators.
AB  - Monitoring voltage dynamics in defined neurons deep in the brain is critical for
      unraveling the function of neuronal circuits but is challenging due to the
      limited performance of existing tools. In particular, while genetically encoded
      voltage indicators have shown promise for optical detection of voltage
      transients, many indicators exhibit low sensitivity when imaged under two-photon
      illumination. Previous studies thus fell short of visualizing voltage dynamics in
      individual neurons in single trials. Here, we report ASAP2s, a novel voltage
      indicator with improved sensitivity. By imaging ASAP2s using random-access multi
      photon microscopy, we demonstrate robust single-trial detection of action
      potentials in organotypic slice cultures. We also show that ASAP2s enables two
      photon imaging of graded potentials in organotypic slice cultures and in
      Drosophila. These results demonstrate that the combination of ASAP2s and fast two
      photon imaging methods enables detection of neural electrical activity with
      subcellular spatial resolution and millisecond-timescale precision.

PMID- 28749339
TI  - PTEN controls glandular morphogenesis through a juxtamembrane beta
      Arrestin1/ARHGAP21 scaffolding complex.
AB  - PTEN controls three-dimensional (3D) glandular morphogenesis by coupling
      juxtamembrane signaling to mitotic spindle machinery. While molecular mechanisms
      remain unclear, PTEN interacts through its C2 membrane-binding domain with the
      scaffold protein beta-Arrestin1. Because beta-Arrestin1 binds and suppresses the
      Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42
      -dependent morphogenic processes through a beta-Arrestin1-ARHGAP21 complex. Here,
      we show that PTEN knockdown (KD) impairs beta-Arrestin1 membrane localization,
      beta-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle
      orientation and 3D glandular morphogenesis. Effects of PTEN deficiency were
      phenocopied by beta-Arrestin1 KD or inhibition of beta-Arrestin1-ARHGAP21
      interactions. Conversely, silencing of ARHGAP21 enhanced Cdc42 activation and
      rescued aberrant morphogenic processes of PTEN-deficient cultures. Expression of
      the PTEN C2 domain mimicked effects of full-length PTEN but a membrane-binding
      defective mutant of the C2 domain abrogated these properties. Our results show
      that PTEN controls multicellular assembly through a membrane-associated
      regulatory protein complex composed of beta-Arrestin1, ARHGAP21 and Cdc42.

PMID- 28749341
TI  - Exciting experiences make neurons less excitable.
AB  - Neurons in the brain of a female mouse that respond to the scent of a given male
      become suppressed after mating.

PMID- 28749340
TI  - Super-resolution imaging of synaptic and Extra-synaptic AMPA receptors with
      different-sized fluorescent probes.
AB  - Previous studies tracking AMPA receptor (AMPAR) diffusion at synapses observed a
      large mobile extrasynaptic AMPAR pool. Using super-resolution microscopy, we
      examined how fluorophore size and photostability affected AMPAR trafficking
      outside of, and within, post-synaptic densities (PSDs) from rats. Organic
      fluorescent dyes (~4 nm), quantum dots, either small (~10 nm diameter; sQDs) or
      big (>20 nm; bQDs), were coupled to AMPARs via different-sized linkers. We find
      that >90% of AMPARs labeled with fluorescent dyes or sQDs were diffusing in
      confined nanodomains in PSDs, which were stable for 15 min or longer. Less than
      10% of sQD-AMPARs were extrasynaptic and highly mobile. In contrast, 5-10% of bQD
      AMPARs were in PSDs and 90-95% were extrasynaptic as previously observed.
      Contrary to the hypothesis that AMPAR entry is limited by the occupancy of open
      PSD 'slots', our findings suggest that AMPARs rapidly enter stable 'nanodomains'
      in PSDs with lifetime >15 min, and do not accumulate in extrasynaptic membranes.

PMID- 28749342
TI  - Broadband Vibration Detection in Tissue Phantoms Using a Fiber Fabry-Perot
      Cavity.
AB  - OBJECTIVE: A fiber optic vibration sensor is developed and characterized with an
      ultrawide dynamic sensing range, from less than 1 Hz to clinical ultrasound
      frequencies near 6 MHz. The vibration sensor consists of a matched pair of fiber
      Bragg gratings coupled to a custom-built signal processing circuit. The
      wavelength of a laser diode is locked to one of the many cavity resonances using
      the Pound-Drever-Hall scheme. METHODS: A calibrated piezoelectric vibration
      element was used to characterize the sensor's strain, temperature, and noise
      responses. To demonstrate its sensing capability, an ultrasound phantom with
      built-in low frequency vibration actuation was constructed. RESULTS: The fiber
      optic senor was shown to simultaneously capture the low frequency vibration and
      the clinical ultrasound transmission waveforms with nanostrain sensitivity.
      CONCLUSION: This miniaturized and sensitive vibration sensor can provide
      comprehensive information regarding strain response and the resultant ultrasound
      waveforms.

PMID- 28749343
TI  - A Potential-Based Inverse Spectral Method to Noninvasively Localize Discordant
      Distributions of Alternans on the Heart From the ECG.
AB  - : T-wave alternans (TWA), defined as the beat-to-beat alternation in amplitude of
      the T-waves, has been shown to be linked to ventricular fibrillation (VF).
      However, current TWA tests have high sensitivity but low specificity in
      determining who is at risk. To overcome this limitation, it might be helpful to
      determine the spatial distribution of any regions on the heart that alternate in
      opposite phase. Understanding these spatial distributions in relation to the
      regular activation of the heart could help explain the mechanism for the genesis
      of VF and thus disambiguate the low specificity of TWA. GOAL: Image the spatial
      distribution of TWA on the heart surface from ECG measurements. METHODS: We
      introduced the inverse spectral method (ISM), a tailored inverse (or
      ElectroCardioGraphic Imaging) solution designed specifically to noninvasively
      image cases of TWA on the heart. RESULTS: We evaluate the ISM on its capacity to
      reliably detect the spatial distributions of TWA compared against a standard TWA
      detection method applied directly to the electrograms on the heart surface. We
      report on results from both a series of synthetic simulations of TWA generated
      using the ECGSIM software and a set of continuous epicardial surface voltage
      recordings from a canine experiment. ISM detected TWA distributions that matched
      the phase of the true underlying out-of-phase regions over and of the heart
      surface, respectively. CONCLUSION: Our results suggest that ISM is capable of
      reliably detecting the different regions present in a TWA distribution across a
      wide variety of TWA locations on the heart in simulation and in the face of
      transients and nonidealities in the canine recordings.

PMID- 28749344
TI  - Giant Magnetoresistive Biosensor Array for Detecting Magnetorelaxation.
AB  - In this paper, a time-domain magnetorelaxometry biosensing scheme is presented
      using giant magnetoresistive (GMR) sensors to measure the fast relaxation
      response of superparamagnetic magnetic nanoparticles (MNPs) in a pulsed magnetic
      field. The system consists of an 8 * 10 GMR sensor array, a Helmholtz coil, an
      electromagnet driver, and an integrator-based analog front-end needed to capture
      the fast relaxation dynamics of MNPs. A custom designed electromagnet driver and
      Helmholtz coil improve the switch-off speed to >5 Oe/MUs, limiting the dead zone
      time to <10 MUs, and thus enables the system to monitor fast relaxation processes
      of 30 nm MNPs. A magnetic correlated double sampling technique is proposed to
      reduce sensor-to-sensor variation by 99.98% while also reducing temperature
      drift, circuit offset, and nonlinearity below the noise level. An optimum
      integration time is calculated and experimentally verified to maximize the SNR.
      Experiments with dried MNPs have shown successful relaxation detection, and
      immunoassay experiments have demonstrated their binding kinetics.

PMID- 28749345
TI  - Noise in Neuronal and Electronic Circuits: A General Modeling Framework and Non
      Monte Carlo Simulation Techniques.
AB  - The brain is extremely energy efficient and remarkably robust in what it does
      despite the considerable variability and noise caused by the stochastic
      mechanisms in neurons and synapses. Computational modeling is a powerful tool
      that can help us gain insight into this important aspect of brain mechanism. A
      deep understanding and computational design tools can help develop robust
      neuromorphic electronic circuits and hybrid neuroelectronic systems. In this
      paper, we present a general modeling framework for biological neuronal circuits
      that systematically captures the nonstationary stochastic behavior of ion
      channels and synaptic processes. In this framework, fine-grained, discrete-state,
      continuous-time Markov chain models of both ion channels and synaptic processes
      are treated in a unified manner. Our modeling framework features a mechanism for
      the automatic generation of the corresponding coarse-grained, continuous-state,
      continuous-time stochastic differential equation models for neuronal variability
      and noise. Furthermore, we repurpose non-Monte Carlo noise analysis techniques,
      which were previously developed for analog electronic circuits, for the
      stochastic characterization of neuronal circuits both in time and frequency
      domain. We verify that the fast non-Monte Carlo analysis methods produce results
      with the same accuracy as computationally expensive Monte Carlo simulations. We
      have implemented the proposed techniques in a prototype simulator, where both
      biological neuronal and analog electronic circuits can be simulated together in a
      coupled manner.

PMID- 28749346
TI  - Attribute And-Or Grammar for Joint Parsing of Human Pose, Parts and Attributes.
AB  - This paper presents an attribute and-or grammar (A-AOG) model for jointly
      inferring human body pose and human attributes in a parse graph with attributes
      augmented to nodes in the hierarchical representation. In contrast to other
      popular methods in the current literature that train separate classifiers for
      poses and individual attributes, our method explicitly represents the
      decomposition and articulation of body parts, and account for the correlations
      between poses and attributes. The A-AOG model is an amalgamation of three
      traditional grammar formulations: (i) Phrase structure grammar representing the
      hierarchical decomposition of the human body from whole to parts; (ii) Dependency
      grammar modeling the geometric articulation by a kinematic graph of the body
      pose; and (iii) Attribute grammar accounting for the compatibility relations
      between different parts in the hierarchy so that their appearances follow a
      consistent style. The parse graph outputs human detection, pose estimation, and
      attribute prediction simultaneously, which are intuitive and interpretable. We
      conduct experiments on two tasks on two datasets, and experimental results
      demonstrate the advantage of joint modeling in comparison with computing poses
      and attributes independently. Furthermore, our model obtains better performance
      over existing methods for both pose estimation and attribute prediction tasks.

PMID- 28749347
TI  - Approximate Message Passing Reconstruction of Quantitative Acoustic Microscopy
      Images.
AB  - A novel framework for compressive sensing (CS) data acquisition and
      reconstruction in quantitative acoustic microscopy (QAM) is presented. Three
      different CS patterns, adapted to the specifics of QAM systems, were investigated
      as an alternative to the current raster-scanning approach. They consist of
      diagonal sampling, a row random, and a spiral scanning pattern and can all
      significantly reduce both the acquisition time and the amount of sampled data.
      For subsequent image reconstruction, we design and implement an innovative
      technique, whereby a recently proposed approximate message passing method is
      adapted to account for the underlying data statistics. A Cauchy maximum a
      posteriori image denoising algorithm is thus employed to account for the non
      Gaussianity of QAM wavelet coefficients. The proposed methods were tested
      retrospectively on experimental data acquired with a 250- or 500-MHz QAM system.
      The experimental data were obtained from a human lymph node sample (250 MHz) and
      human cornea (500 MHz). Reconstruction results showed that the best performance
      is obtained using a spiral sensing pattern combined with the Cauchy denoiser in
      the wavelet domain. The spiral sensing matrix reduced the number of spatial
      samples by a factor of 2 and led to an excellent peak signal-to-noise ratio of
      43.21 dB when reconstructing QAM speed-of-sound images of a human lymph node.
      These results demonstrate that the CS approach could significantly improve
      scanning time, while reducing costs of future QAM systems.

PMID- 28749348
TI  - Fast Simulation of Dynamic Ultrasound Images Using the GPU.
AB  - Simulated ultrasound data is a valuable tool for development and validation of
      quantitative image analysis methods in echocardiography. Unfortunately,
      simulation time can become prohibitive for phantoms consisting of a large number
      of point scatterers. The COLE algorithm by Gao et al. is a fast convolution-based
      simulator that trades simulation accuracy for improved speed. We present highly
      efficient parallelized CPU and GPU implementations of the COLE algorithm with an
      emphasis on dynamic simulations involving moving point scatterers. We argue that
      it is crucial to minimize the amount of data transfers from the CPU to achieve
      good performance on the GPU. We achieve this by storing the complete trajectories
      of the dynamic point scatterers as spline curves in the GPU memory. This leads to
      good efficiency when simulating sequences consisting of a large number of frames,
      such as B-mode and tissue Doppler data for a full cardiac cycle. In addition, we
      propose a phase-based subsample delay technique that efficiently eliminates
      flickering artifacts seen in B-mode sequences when COLE is used without enough
      temporal oversampling. To assess the performance, we used a laptop computer and a
      desktop computer, each equipped with a multicore Intel CPU and an NVIDIA GPU.
      Running the simulator on a high-end TITAN X GPU, we observed two orders of
      magnitude speedup compared to the parallel CPU version, three orders of magnitude
      speedup compared to simulation times reported by Gao et al. in their paper on
      COLE, and a speedup of 27000 times compared to the multithreaded version of Field
      II, using numbers reported in a paper by Jensen. We hope that by releasing the
      simulator as an open-source project we will encourage its use and further
      development.

PMID- 28749349
TI  - Extensive Benchmark and Survey of Modeling Methods for Scene Background
      Initialization.
AB  - Scene background initialization is the process by which a method tries to recover
      the background image of a video without foreground objects in it. Having a clear
      understanding about which approach is more robust and/or more suited to a given
      scenario is of great interest to many end users or practitioners. The aim of this
      paper is to provide an extensive survey of scene background initialization
      methods as well as a novel benchmarking framework. The proposed framework
      involves several evaluation metrics and state-of-the-art methods, as well as the
      largest video data set ever made for this purpose. The data set consists of
      several camera-captured videos that: 1) span categories focused on various
      background initialization challenges; 2) are obtained with different cameras of
      different lengths, frame rates, spatial resolutions, lighting conditions, and
      levels of compression; and 3) contain indoor and outdoor scenes. The wide variety
      of our data set prevents our analysis from favoring a certain family of
      background initialization methods over others. Our evaluation framework allows us
      to quantitatively identify solved and unsolved issues related to scene background
      initialization. We also identify scenarios for which state-of-the-art methods
      systematically fail.

PMID- 28749350
TI  - Distributed Adaptive Binary Quantization for Fast Nearest Neighbor Search.
AB  - Hashing has been proved an attractive technique for fast nearest neighbor search
      over big data. Compared with the projection based hashing methods, prototype
      based ones own stronger power to generate discriminative binary codes for the
      data with complex intrinsic structure. However, existing prototype-based methods,
      such as spherical hashing and K-means hashing, still suffer from the ineffective
      coding that utilizes the complete binary codes in a hypercube. To address this
      problem, we propose an adaptive binary quantization (ABQ) method that learns a
      discriminative hash function with prototypes associated with small unique binary
      codes. Our alternating optimization adaptively discovers the prototype set and
      the code set of a varying size in an efficient way, which together robustly
      approximate the data relations. Our method can be naturally generalized to the
      product space for long hash codes, and enjoys the fast training linear to the
      number of the training data. We further devise a distributed framework for the
      large-scale learning, which can significantly speed up the training of ABQ in the
      distributed environment that has been widely deployed in many areas nowadays. The
      extensive experiments on four large-scale (up to 80 million) data sets
      demonstrate that our method significantly outperforms state-of-the-art hashing
      methods, with up to 58.84% performance gains relatively.

PMID- 28749351
TI  - Point Light Source Position Estimation From RGB-D Images by Learning Surface
      Attributes.
AB  - Light source position (LSP) estimation is a difficult yet an important problem in
      computer vision. A common approach for estimating the LSP assumes Lambert's law.
      However, in real-world scenes, Lambert's law does not hold for all different
      types of surfaces. Instead of assuming all that surfaces follow Lambert's law,
      our approach classifies image surface segments based on their photometric and
      geometric surface attributes (i.e. glossy, matte, curved, and so on) and assigns
      weights to image surface segments based on their suitability for LSP estimation.
      In addition, we propose the use of the estimated camera pose to globally
      constrain LSP for RGB-D video sequences. Experiments on Boom and a newly
      collected RGB-D video data sets show that the state-of-the-art methods are
      outperformed by the proposed method. The results demonstrate that weighting image
      surface segments based on their attributes outperform the state-of-the-art
      methods in which the image surface segments are considered to equally contribute.
      In particular, by using the proposed surface weighting, the angular error for LSP
      estimation is reduced from 12.6 degrees  to 8.2 degrees  and 24.6 degrees  to 4.8
      degrees  for Boom and RGB-D video data sets, respectively. Moreover, using the
      camera pose to globally constrain LSP provides higher accuracy (4.8 degrees )
      compared with using single frames (8.5 degrees ).

PMID- 28749352
TI  - Example-Based Image Colorization Using Locality Consistent Sparse Representation.
AB  - Image colorization aims to produce a natural looking color image from a given
      gray-scale image, which remains a challenging problem. In this paper, we propose
      a novel example-based image colorization method exploiting a new locality
      consistent sparse representation. Given a single reference color image, our
      method automatically colorizes the target gray-scale image by sparse pursuit. For
      efficiency and robustness, our method operates at the superpixel level. We
      extract low-level intensity features, mid-level texture features, and high-level
      semantic features for each superpixel, which are then concatenated to form its
      descriptor. The collection of feature vectors for all the superpixels from the
      reference image composes the dictionary. We formulate colorization of target
      superpixels as a dictionary-based sparse reconstruction problem. Inspired by the
      observation that superpixels with similar spatial location and/or feature
      representation are likely to match spatially close regions from the reference
      image, we further introduce a locality promoting regularization term into the
      energy formulation, which substantially improves the matching consistency and
      subsequent colorization results. Target superpixels are colorized based on the
      chrominance information from the dominant reference superpixels. Finally, to
      further improve coherence while preserving sharpness, we develop a new edge
      preserving filter for chrominance channels with the guidance from the target gray
      scale image. To the best of our knowledge, this is the first work on sparse
      pursuit image colorization from single reference images. Experimental results
      demonstrate that our colorization method outperforms the state-of-the-art
      methods, both visually and quantitatively using a user study.

PMID- 28749353
TI  - Mesh Denoising with (Geo)Metric Fidelity.
AB  - Working with noisy meshes and aiming at providing high-fidelity 3D object models
      without tampering the metric quality of the acquisitions, we propose a mesh
      denoising technique that, through a normal-diffusion process guided by a
      curvature saliency map, is able to preserve and emphasize the natural object
      features, concurrently allowing the introduction of a bound on the maximum
      distance from the original model. Moreover, both the position of the mesh
      vertices and the edge orientations are optimized through a tailored geometric
      aliasing correction. Thanks to an efficiently parallelized procedure, we are able
      to process even large models almost instantly with a parameter configuration that
      does not depend on the scale of the object. An essential survey on mesh denoising
      is also presented which is functional to the definition of a common framework
      where to set up our solutions and the related technical and experimental
      comparisons. The proposed results prove the effectiveness of our method,
      especially on the challenging target application profiles. Where competing
      techniques tend to inappropriately recover sharp edges while deforming the
      surrounding geometry or, on the contrary, to oversmooth shallow features, our
      method protects and enhances the natural object features and effectively reduces
      scanning noise on the smooth parts, while guaranteeing the prescribed metric
      fidelity to the input model.

PMID- 28749354
TI  - Real-time Cloth Rendering with Fiber-level Detail.
AB  - Modeling cloth with fiber-level geometry can produce highly realistic details.
      However, rendering fiber-level cloth models not only has a high memory cost but
      it also has a high computation cost even for offline rendering applications. In
      this paper we present a real-time fiber-level cloth rendering method for current
      GPUs. Our method procedurally generates fiber-level geometric details on-the-fly
      using yarn-level control points for minimizing the data transfer to the GPU. We
      also reduce the rasterization operations by collectively representing the fibers
      near the center of each ply that form the yarn structure. Moreover, we employ a
      level-of-detail strategy to minimize or completely eliminate the generation of
      fiber-level geometry that would have little or no impact on the final rendered
      image. Furthermore, we introduce a simple self-shadow computation method that
      allows lighting with self-shadows using relatively low-resolution shadow maps. We
      also provide a simple distance-based ambient occlusion approximation as well as
      an ambient illumination precomputation approach. Finally, we discuss how to use a
      physical-based shading model with our fiber-level cloth rendering method. We
      demonstrate the effectiveness of our approach by comparing our simplified fiber
      geometry to procedurally generated references and display knitwear containing
      more than a hundred million individual fiber curves at real-time frame rates with
      shadows and ambient occlusion.

PMID- 28749355
TI  - Hardware Accelerator for the Multifractal Analysis of DNA Sequences.
AB  - The multifractal analysis has allowed to quantify the genetic variability and non
      linear stability along the human genome sequence. It has some implications in
      explaining several genetic diseases given by some chromosome abnormalities, among
      other genetic particularities. The multifractal analysis of a genome is carried
      out by dividing the complete DNA sequence in smaller fragments and calculating
      the generalized dimension spectrum of each fragment using the chaos game
      representation and the box-counting method. This is a time consuming process
      because it involves the processing of large data sets using floating-point
      representation. In order to reduce the computation time, we designed an
      application-specific processor, here called multifractal processor, which is
      based on our proposed hardware-oriented algorithm for calculating efficiently the
      generalized dimension spectrum of DNA sequences. The multifractal processor was
      implemented on a low-cost SoC-FPGA and was verified by processing a complete
      human genome. The execution time and numeric results of the Multifractal
      processor were compared with the results obtained from the software
      implementation executed in a 20-core workstation, achieving a speed up of 2.6x
      and an average error of 0.0003 percent.

PMID- 28749356
TI  - Improving Alzheimer's Disease Classification by Combining Multiple Measures.
AB  - Several anatomical magnetic resonance imaging (MRI) markers for Alzheimer's
      disease (AD) have been identified. Cortical gray matter volume, cortical
      thickness, and subcortical volume have been used successfully to assist the
      diagnosis of Alzheimer's disease including its early warning and developing
      stages, e.g., mild cognitive impairment (MCI) including MCI converted to AD
      (MCIc) and MCI not converted to AD (MCInc). Currently, these anatomical MRI
      measures have mainly been used separately. Thus, the full potential of anatomical
      MRI scans for AD diagnosis might not yet have been used optimally. Meanwhile,
      most studies currently only focused on morphological features of regions of
      interest (ROIs) or interregional features without considering the combination of
      them. To further improve the diagnosis of AD, we propose a novel approach of
      extracting ROI features and interregional features based on multiple measures
      from MRI images to distinguish AD, MCI (including MCIc and MCInc), and health
      control (HC). First, we construct six individual networks based on six different
      anatomical measures (i.e., CGMV, CT, CSA, CC, CFI, and SV) and Automated
      Anatomical Labeling (AAL) atlas for each subject. Then, for each individual
      network, we extract all node (ROI) features and edge (interregional) features,
      and denoted as node feature set and edge feature set, respectively. Therefore, we
      can obtain six node feature sets and six edge feature sets from six different
      anatomical measures. Next, each feature within a feature set is ranked by -score
      in descending order, and the top ranked features of each feature set are applied
      to MKBoost algorithm to obtain the best classification accuracy. After obtaining
      the best classification accuracy, we can get the optimal feature subset and the
      corresponding classifier for each node or edge feature set. Afterwards, to
      investigate the classification performance with only node features, we proposed a
      weighted multiple kernel learning (wMKL) framework to combine these six optimal
      node feature subsets, and obtain a combined classifier to perform AD
      classification. Similarly, we can obtain the classification performance with only
      edge features. Finally, we combine both six optimal node feature subsets and six
      optimal edge feature subsets to further improve the classification performance.
      Experimental results show that the proposed method outperforms some state-of-the
      art methods in AD classification, and demonstrate that different measures contain
      complementary information.

PMID- 28749357
TI  - $k$ -Times Markov Sampling for SVMC.
AB  - Support vector machine (SVM) is one of the most widely used learning algorithms
      for classification problems. Although SVM has good performance in practical
      applications, it has high algorithmic complexity as the size of training samples
      is large. In this paper, we introduce SVM classification (SVMC) algorithm based
      on -times Markov sampling and present the numerical studies on the learning
      performance of SVMC with -times Markov sampling for benchmark data sets. The
      experimental results show that the SVMC algorithm with -times Markov sampling not
      only have smaller misclassification rates, less time of sampling and training,
      but also the obtained classifier is more sparse compared with the classical SVMC
      and the previously known SVMC algorithm based on Markov sampling. We also give
      some discussions on the performance of SVMC with -times Markov sampling for the
      case of unbalanced training samples and large-scale training samples.

PMID- 28749358
TI  - A New Neural Dynamic Classification Algorithm.
AB  - The keys for the development of an effective classification algorithm are: 1)
      discovering feature spaces with large margins between clusters and close
      proximity of the classmates and 2) discovering the smallest number of the
      features to perform accurate classification. In this paper, a new supervised
      classification algorithm, called neural dynamic classification (NDC), is
      presented with the goal of: 1) discovering the most effective feature spaces and
      2) finding the optimum number of features required for accurate classification
      using the patented robust neural dynamic optimization model of Adeli and Park.
      The new classification algorithm is compared with the probabilistic neural
      network (PNN), enhanced PNN (EPNN), and support vector machine using two sets of
      classification problems. The first set consists of five standard benchmark
      problems. The second set is a large benchmark problem called Mixed National
      Institute of Standards and Technology database of handwritten digits. In general,
      NDC yields the most accurate classification results followed by EPNN. A beauty of
      the new algorithm is the smoothness of convergence curves which is an indication
      of robustness and good performance of the algorithm. The main aim is to maximize
      the prediction accuracy.

PMID- 28749359
TI  - Systolic Time Interval Estimation Using Continuous Wave Radar With On-Body
      Antennas.
AB  - : The estimation of systolic time intervals (STIs) is done using continuous wave
      (CW) radar at 2.45 GHz with an on-body antenna. MOTIVATION: In the state of the
      art, typically bioimpedance, heart sounds and/or ultrasound are used to measure
      STIs. All three methods suffer from insufficient accuracy of STI estimation due
      to various reasons. CW radar is investigated for its ability to overcome the
      deficiencies in the state of the art. METHODS: Ten healthy male subjects aged 25
      45 were asked to lie down at a 30 incline. Recordings of 60 s were taken without
      breathing and with paced breathing. Heart sounds, electrocardiogram, respiration,
      and impedance cardiogram were measured simultaneously as reference. The radar
      antennas were placed at two positions on the chest. The antennas were placed
      directly on the body as well as with cotton textile in between. The beat to beat
      STIs have been determined from the reference signals as well as CW radar signals.
      RESULTS: The results indicate that CW radar can be used to estimate STIs in
      ambulatory monitoring. SIGNIFICANCE: The results pave way to a potentially more
      compact method of estimating STIs, which can be integrated into a wearable
      device.

PMID- 28749360
TI  - Multi-Hypergraph Learning for Incomplete Multimodality Data.
AB  - Multi-modality data convey complementary information that can be used to improve
      the accuracy of prediction models in disease diagnosis. However, effectively
      integrating multi-modality data remains a challenging problem, especially when
      the data are incomplete. For instance, more than half of the subjects in the
      Alzheimer's disease neuroimaging initiative (ADNI) database have no
      fluorodeoxyglucose positron emission tomography and cerebrospinal fluid data.
      Currently, there are two commonly used strategies to handle the problem of
      incomplete data: 1) discard samples having missing features; and 2) impute those
      missing values via specific techniques. In the first case, a significant amount
      of useful information is lost and, in the second case, additional noise and
      artifacts might be introduced into the data. Also, previous studies generally
      focus on the pairwise relationships among subjects, without considering their
      underlying complex (e.g., high-order) relationships. To address these issues, in
      this paper, we propose a multi-hypergraph learning method for dealing with
      incomplete multimodality data. Specifically, we first construct multiple
      hypergraphs to represent the high-order relationships among subjects by dividing
      them into several groups according to the availability of their data modalities.
      A hypergraph regularized transductive learning method is then applied to these
      groups for automatic diagnosis of brain diseases. Extensive evaluation of the
      proposed method using all subjects in the baseline ADNI database indicates that
      our method achieves promising results in AD/MCI classification, compared with the
      state-of-the-art methods.

PMID- 28749361
TI  - Output-Feedback Control of Unknown Linear Discrete-Time Systems With Stochastic
      Measurement and Process Noise via Approximate Dynamic Programming.
AB  - This paper studies the optimal output-feedback control problem for unknown linear
      discrete-time systems with stochastic measurement and process noise. A dithered
      Bellman equation with the innovation covariance matrix is constructed via the
      expectation operator given in the form of a finite summation. On this basis, an
      output-feedback-based approximate dynamic programming method is developed, where
      the terms depending on the innovation covariance matrix are available with the
      aid of the innovation covariance matrix identified beforehand. Therefore, by
      iterating the Bellman equation, the resulting value function can converge to the
      optimal one in the presence of the aforementioned noise, and the nearly optimal
      control laws are delivered. To show the effectiveness and the advantages of the
      proposed approach, a simulation example and a velocity control experiment on a dc
      machine are employed.

PMID- 28749362
TI  - Incremental Codebook Adaptation for Visual Representation and Categorization.
AB  - The bag-of-visual-words model is widely used for visual content analysis. For
      visual data, the codebook plays an important role for efficient representation.
      However, the codebook has to be relearned with the changes of training images.
      Once the codebook is changed, the encoding parameters of local features have to
      be recomputed. To alleviate this problem, in this paper, we propose an
      incremental codebook adaptation method for efficient visual representation.
      Instead of learning a new codebook, we gradually adapt a prelearned codebook
      using new images in an incremental way. To make use of the prelearned codebook,
      we try to make changes to the prelearned codebook with sparsity constraint and
      low-rank correlation. Besides, we also encode visually similar local features
      within a neighborhood to take advantage of locality information and ensure the
      encoded parameters are consistent. To evaluate the effectiveness of the proposed
      method, we apply the proposed method for categorization tasks on several public
      image datasets. Experimental results prove the effectiveness and usefulness of
      the proposed method over other codebook-based methods.

PMID- 28749363
TI  - Distributed Parametric Consensus Optimization With an Application to Model
      Predictive Consensus Problem.
AB  - In this paper, we study a special class of distributed convex optimization
      problems-distributed parametric consensus optimization problem (DPCOP), for which
      a two-stage optimization method including primal decomposition and distributed
      consensus is provided. Different from traditional distributed optimization
      problems driving all the local states to a common value, DPCOP aims to solve a
      system-wide problem with partial common parameters shared amongst local agents in
      a distributed way. To relax the restriction on the topology, a distributed
      projected subgradient method is applied in distributed consensus stage to achieve
      the consensus of local estimated parameters, while the subgradients can be
      obtained by solving a multiparametric problem locally. For a special class of
      DPCOPs, a discrete-time distributed algorithm with exponential rate of
      convergence is provided. Furthermore, the proposed two-stage optimization method
      is applied to a distributed model predictive consensus problem in order to reach
      an optimal output consensus at equilibrium points for all agents. The stability
      analysis for the proposed algorithm is further given. Two case studies on a
      heterogenous multiagent system with high-order integrator dynamics are provided
      to verify the effectiveness of proposed methods.

PMID- 28749364
TI  - Bayesian Random Vector Functional-Link Networks for Robust Data Modeling.
AB  - Random vector functional-link (RVFL) networks are randomized multilayer
      perceptrons with a single hidden layer and a linear output layer, which can be
      trained by solving a linear modeling problem. In particular, they are generally
      trained using a closed-form solution of the (regularized) least-squares approach.
      This paper introduces several alternative strategies for performing full Bayesian
      inference (BI) of RVFL networks. Distinct from standard or classical approaches,
      our proposed Bayesian training algorithms allow to derive an entire probability
      distribution over the optimal output weights of the network, instead of a single
      pointwise estimate according to some given criterion (e.g., least-squares). This
      provides several known advantages, including the possibility of introducing
      additional prior knowledge in the training process, the availability of an
      uncertainty measure during the test phase, and the capability of automatically
      inferring hyper-parameters from given data. In this paper, two BI algorithms for
      regression are first proposed that, under some practical assumptions, can be
      implemented by a simple iterative process with closed-form computations.
      Simulation results show that one of the proposed algorithms, Bayesian RVFL, is
      able to outperform standard training algorithms for RVFL networks with a proper
      regularization factor selected carefully via a line search procedure. A general
      strategy based on variational inference is also presented, with an application to
      data modeling problems with noisy outputs or outliers. As we discuss in this
      paper, using recent advances in automatic differentiation this strategy can be
      applied to a wide range of additional situations in an immediate fashion.

PMID- 28749365
TI  - Discriminative Joint-Feature Topic Model With Dual Constraints for WCE
      Classification.
AB  - Wireless capsule endoscopy (WCE) enables clinicians to examine the digestive
      tract without any surgical operations, at the cost of a large amount of images to
      be analyzed. The main challenge for automatic computer-aided diagnosis arises
      from the difficulty of robust characterization of these images. To tackle this
      problem, a novel discriminative joint-feature topic model (DJTM) with dual
      constraints is proposed to classify multiple abnormalities in WCE images. We
      first propose a joint-feature probabilistic latent semantic analysis (PLSA)
      model, where color and texture descriptors extracted from same image patches are
      jointly modeled with their conditional distributions. Then the proposed dual
      constraints: visual words importance and local image manifold are embedded into
      the joint-feature PLSA model simultaneously to obtain discriminative latent
      semantic topics. The visual word importance is proposed in our DJTM to guarantee
      that visual words with similar importance come from close latent topics while the
      local image manifold constraint enforces that images within the same category
      share similar latent topics. Finally, each image is characterized by distribution
      of latent semantic topics instead of low level features. Our proposed DJTM showed
      an excellent overall recognition accuracy 90.78%. Comprehensive comparison
      results demonstrate that our method outperforms existing multiple abnormalities
      classification methods for WCE images.

PMID- 28749366
TI  - Robust Learning With Kernel Mean -Power Error Loss.
AB  - Correntropy is a second order statistical measure in kernel space, which has been
      successfully applied in robust learning and signal processing. In this paper, we
      define a nonsecond order statistical measure in kernel space, called the kernel
      mean- power error (KMPE), including the correntropic loss (C-Loss) as a special
      case. Some basic properties of KMPE are presented. In particular, we apply the
      KMPE to extreme learning machine (ELM) and principal component analysis (PCA),
      and develop two robust learning algorithms, namely ELM-KMPE and PCA-KMPE.
      Experimental results on synthetic and benchmark data show that the developed
      algorithms can achieve better performance when compared with some existing
      methods.

PMID- 28749368
TI  - Updating the NIEHS Strategic Plan.

PMID- 28749367
TI  - Genome-wide Association Study of Susceptibility to Particulate Matter-Associated
      QT Prolongation.
AB  - BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been
      associated with increases in QT interval duration (QT). However, innate
      susceptibility to PM-associated QT prolongation has not been characterized.
      OBJECTIVE: To characterize genetic susceptibility to PM-associated QT
      prolongation in a multi-racial/ethnic, genome-wide association study (GWAS).
      METHODS: Using repeated electrocardiograms (1986-2004), longitudinal data on
      PM<10 MUm in diameter (PM10), and generalized estimating equations methods
      adapted for low-prevalence exposure, we estimated approximately 2.5*106 SNP*PM10
      interactions among nine Women's Health Initiative clinical trials and
      Atherosclerosis Risk in Communities Study subpopulations (n=22,158), then
      combined subpopulation-specific results in a fixed-effects, inverse variance
      weighted meta-analysis. RESULTS: A common variant (rs1619661; coded allele: T)
      significantly modified the QT-PM10 association (p=2.11*10-8). At PM10
      concentrations >90th percentile, QT increased 7 ms across the CC and TT
      genotypes: 397 (95% confidence interval: 396, 399) to 404 (403, 404) ms. However,
      QT changed minimally across rs1619661 genotypes at lower PM10 concentrations. The
      rs1619661 variant is on chromosome 10, 132 kilobase (kb) downstream from
      <em>CXCL12</em>, which encodes a chemokine, stromal cell-derived factor 1, that
      is expressed in cardiomyocytes and decreases calcium influx across the L-type
      Ca2+ channel. CONCLUSIONS: The findings suggest that biologically plausible
      genetic factors may alter susceptibility to PM10-associated QT prolongation in
      populations protected by the U.S. Environmental Protection Agency's National
      Ambient Air Quality Standards. Independent replication and functional
      characterization are necessary to validate our findings.
      https://doi.org/10.1289/EHP347

PMID- 28749369
TI  - Race/Ethnicity, Socioeconomic Status, Residential Segregation, and Spatial
      Variation in Noise Exposure in the Contiguous United States.
AB  - BACKGROUND: Prior research has reported disparities in environmental exposures in
      the United States, but, to our knowledge, no nationwide studies have assessed
      inequality in noise pollution. OBJECTIVES: We aimed to a) assess racial/ethnic
      and socioeconomic inequalities in noise pollution in the contiguous United
      States; and b) consider the modifying role of metropolitan level racial
      residential segregation. METHODS: We used a geospatial sound model to estimate
      census block group-level median (L50) nighttime and daytime noise exposure and
      90th percentile (L10) daytime noise exposure. Block group variables from the 2006
      2010 American Community Survey (ACS) included race/ethnicity, education, income,
      poverty, unemployment, homeownership, and linguistic isolation. We estimated
      associations using polynomial terms in spatial error models adjusted for total
      population and population density. We also evaluated the relationship between
      race/ethnicity and noise, stratified by levels of metropolitan area racial
      residential segregation, classified using a multigroup dissimilarity index.
      RESULTS: Generally, estimated nighttime and daytime noise levels were higher for
      census block groups with higher proportions of nonwhite and lower-socioeconomic
      status (SES) residents. For example, estimated nighttime noise levels in urban
      block groups with 75% vs. 0% black residents were 46.3 A-weighted decibels (dBA)
      [interquartile range (IQR): 44.3-47.8 dBA] and 42.3 dBA (IQR: 40.4-45.5 dBA),
      respectively. In urban block groups with 50% vs. 0% of residents living below
      poverty, estimated nighttime noise levels were 46.9 dBA (IQR: 44.7-48.5 dBA) and
      44.0 dBA (IQR: 42.2-45.5 dBA), respectively. Block groups with the highest
      metropolitan area segregation had the highest estimated noise exposures,
      regardless of racial composition. Results were generally consistent between urban
      and suburban/rural census block groups, and for daytime and nighttime noise and
      robust to different spatial weight and neighbor definitions. CONCLUSIONS: We
      found evidence of racial/ethnic and socioeconomic differences in model-based
      estimates of noise exposure throughout the United States. Additional research is
      needed to determine if differences in noise exposure may contribute to health
      disparities in the United States. https://doi.org/10.1289/EHP898

PMID- 28749370
TI  - Hierarchical nanosheet-based Ni3S2 microspheres grown on Ni foam for high
      performance all-solid-state asymmetric supercapacitors.
AB  - The hierarchical nanosheet-based Ni3S2 microspheres directly grew on Ni foam
      using a two-step hydrothermal method. The microsphere with a diameter of ~1
      microns and a rough surface was well connected to each other without any binders
      to provide a larger specific surface area, shorter ion/electron diffusion paths,
      richer electroactive sites as a supercapacitor electrode. As a three-electrode
      supercapacitor, it delivers a high specific capacity of 981.8 F g-1 at 2 A g-1,
      an excellent rate capability of 436.4 F g-1 at 12 A g-1, and a good cycling
      stability of 950.9 F g-1 with 96.9% retention after 1000 cycles at 2 A g-1.
      Furthermore, an asymmetric supercapacitor based on Ni3S2-microsphere as a
      positive electrode and active carbon as a negative electrode shows a high energy
      density of 29.4 Wh kg-1 at 324.5 W kg-1 and a high power density of 3197.6 W kg-1
      at 15.1 Wh kg-1. This work demonstrates that nanosheet-based Ni3S2 microspheres
      coated Ni foam can be an effective electrode for a real supercapacitor.

PMID- 28749371
TI  - Probing dimensionality using a simplified 4-probe method.
AB  - 4-probe electrical measurements have been in existence for many decades. One of
      the most useful aspects of the 4-probe method is that it is not only possible to
      find the resistivity of a sample (independently of the contact resistances), but
      that it is also possible to probe the dimensionality of the sample. In theory,
      this is straightforward to achieve by measuring the 4-probe resistance as a
      function of probe separation. In practice, it is challenging to move all four
      probes with sufficient precision over the necessary range. Here, we present an
      alternative approach. We demonstrate that the dimensionality of the conductive
      path within a sample can be directly probed using a modified 4-probe method in
      which an unconventional geometry is exploited; three of the probes are rigidly
      fixed, and the position of only one probe is changed. This allows 2D and 3D (and
      other) contributions the to resistivity to be readily disentangled. The required
      experimental instrumentation can be vastly simplified relative to traditional
      variable spacing 4-probe instruments.

PMID- 28749372
TI  - 3D-printing a 'family' of biomimetic models to explain armored grasping in
      syngnathid fishes.
AB  - Seahorses and pipehorses evolved at least two independent strategies for tail
      grasping, despite being armored with a heavy body plating. To help explain
      mechanical trade-offs associated with the different designs, we created a
      'family' of 3D-printed models that mimic variations in the presence and size of
      their armored plates. We measured the performance of the biomimetic proxies
      across several mechanical metrics, representative of their protective and
      prehensile capacities. Our results show that the models mimicking the tails of
      seahorses are the best all-around performers, while those of the distal-most,
      prehensile region of pipehorses are more flexible, but less protected. The
      comparison also reveals that different adaptive strategies provide different task
      specific performance advantages, which could be leveraged for the design of
      armored manipulators or other bio-inspired technologies.

PMID- 28749373
TI  - Dosimetric evaluation of a commercial proton spot scanning Monte-Carlo dose
      algorithm: comparisons against measurements and simulations.
AB  - RaySearch Americas Inc. (NY) has introduced a commercial Monte Carlo dose
      algorithm (RS-MC) for routine clinical use in proton spot scanning. In this
      report, we provide a validation of this algorithm against phantom measurements
      and simulations in the GATE software package. We also compared the performance of
      the RayStation analytical algorithm (RS-PBA) against the RS-MC algorithm. A beam
      model (G-MC) for a spot scanning gantry at our proton center was implemented in
      the GATE software package. The model was validated against measurements in a
      water phantom and was used for benchmarking the RS-MC. Validation of the RS-MC
      was performed in a water phantom by measuring depth doses and profiles for three
      spread-out Bragg peak (SOBP) beams with normal incidence, an SOBP with oblique
      incidence, and an SOBP with a range shifter and large air gap. The RS-MC was also
      validated against measurements and simulations in heterogeneous phantoms created
      by placing lung or bone slabs in a water phantom. Lateral dose profiles near the
      distal end of the beam were measured with a microDiamond detector and compared to
      the G-MC simulations, RS-MC and RS-PBA. Finally, the RS-MC and RS-PBA were
      validated against measured dose distributions in an Alderson-Rando (AR) phantom.
      Measurements were made using Gafchromic film in the AR phantom and compared to
      doses using the RS-PBA and RS-MC algorithms. For SOBP depth doses in a water
      phantom, all three algorithms matched the measurements to within  +/-3% at all
      points and a range within 1 mm. The RS-PBA algorithm showed up to a 10%
      difference in dose at the entrance for the beam with a range shifter and  >30 cm
      air gap, while the RS-MC and G-MC were always within 3% of the measurement. For
      an oblique beam incident at 45 degrees , the RS-PBA algorithm showed up to 6%
      local dose differences and broadening of distal fall-off by 5 mm. Both the RS-MC
      and G-MC accurately predicted the depth dose to within  +/-3% and distal fall-off
      to within 2 mm. In an anthropomorphic phantom, the gamma index (dose tolerance  =
      3%, distance-to-agreement  =  3 mm) was greater than 90% for six out of seven
      planes using the RS-MC, and three out seven for the RS-PBA. The RS-MC algorithm
      demonstrated improved dosimetric accuracy over the RS-PBA in the presence of
      homogenous, heterogeneous and anthropomorphic phantoms. The computation
      performance of the RS-MC was similar to the RS-PBA algorithm. For complex disease
      sites like breast, head and neck, and lung cancer, the RS-MC algorithm will
      provide significantly more accurate treatment planning.

PMID- 28749374
TI  - Nitrogen doped RGO-Co3O4 nanograin cookies: highly porous and robust catalyst for
      removing nitrophenol from waste water.
AB  - The fabrication of nanograins with a uniform morphology wrapped with reduced
      graphene oxide (RGO) in a designed manner is critical for obtaining a large
      surface, high porosity and efficient catalytic ability at mild conditions. Hybrid
      structures of metal oxides decorated on two-dimensional (2D) RGO lacked an
      interface and channels between the individual grains and RGO. The present work
      focuses on the synthesis of RGO-wrapped Co3O4 nanograin architecture in micron
      sized polyhedrons and the ability to reduce aromatic nitro compounds. Doping N in
      the designed microstructure polyhedrons resulted in very large surface area
      (1085.6 m2 g-1) and pore density (0.47 m3 g-1) microcages. Binding energies from
      x-ray photoelectron spectroscopy (XPS) and Raman intensities confirmed the
      presence of doped N and RGO-wrapped around Co3O4 nanograins. However, the
      morphology and microstructure was supported by FESEM and HRTEM images revealing
      the fabrication of high integrity RGO-Co3O4 microstructure hybrids composed of a
      10 nm grain size with narrower grain size distribution. Ammonia treatment
      produced interconnected channels and dumbbell pores that facilitated ion exchange
      between the catalyst surface and the liquid medium at the grain boundary
      interfaces, and offered less mass transport resistance providing fast adsorption
      of reactants and desorption of the product causing surface renewal. Prepared N
      RGO-Co3O4 shows the largest percentage reduction (96%) of p-nitrophenol (p-NP) at
      room temperature as compared to pure Co3O4 and RGO-Co3O4 nanograin
      microstructures over 10 min. Fabricated architectures can be applied effectively
      for fast and facile treatment of industrial waste streams with complex organic
      molecules.

PMID- 28749375
TI  - Towards fast online intrafraction replanning for free-breathing stereotactic body
      radiation therapy with the MR-linac.
AB  - The hybrid MRI-radiotherapy machines, like the MR-linac (Elekta AB, Stockholm,
      Sweden) installed at the UMC Utrecht (Utrecht, The Netherlands), will be able to
      provide real-time patient imaging during treatment. In order to take advantage of
      the system's capabilities and enable online adaptive treatments, a new generation
      of software should be developed, ranging from motion estimation to treatment plan
      adaptation. In this work we present a proof of principle adaptive pipeline
      designed for high precision stereotactic body radiation therapy (SBRT) suitable
      for sites affected by respiratory motion, like renal cell carcinoma (RCC). We
      utilized our research MRL treatment planning system (MRLTP) to simulate a single
      fraction 25 Gy free-breathing SBRT treatment for RCC by performing inter-beam
      replanning for two patients and one volunteer. The simulated pipeline included a
      combination of (pre-beam) 4D-MRI and (online) 2D cine-MR acquisitions. The 4DMRI
      was used to generate the mid-position reference volume, while the cine-MRI, via
      an in-house motion model, provided three-dimensional (3D) deformable vector
      fields (DVFs) describing the anatomical changes during treatment. During the
      treatment fraction, at an inter-beam interval, the mid-position volume of the
      patient was updated and the delivered dose was accurately reconstructed on the
      underlying motion calculated by the model. Fast online replanning, targeting the
      latest anatomy and incorporating the previously delivered dose was then simulated
      with MRLTP. The adaptive treatment was compared to a conventional mid-position
      SBRT plan with a 3 mm planning target volume margin reconstructed on the same
      motion trace. We demonstrate that our system produced tighter dose distributions
      and thus spared the healthy tissue, while delivering more dose to the target. The
      pipeline was able to account for baseline variations/drifts that occurred during
      treatment ensuring target coverage at the end of the treatment fraction.

PMID- 28749376
TI  - Ag nanoparticle decorated molybdenum oxide structures: growth, characterization,
      DFT studies and their application to enhanced field emission.
AB  - We report a simple single step growth of alpha-MoO3 structures and energetically
      suitable site specific Ag nanoparticle (NP) decorated alpha-MoO3 structures on
      varied substrates, having almost similar morphologies and oxygen vacancies. We
      elucidate possible growth mechanisms in light of experimental findings and
      density functional theory (DFT) calculations. We experimentally establish and
      verified by DFT calculations that the MoO3(010) surface is a weakly interacting
      and stable surface compared to other orientations. From DFT study, the binding
      energy is found to be higher for (100) and (001) surfaces (~-0.98 eV), compared
      to the (010) surface (~-0.15 eV) and thus it is likely that Ag NP formation is
      not favorable on the MoO3(010) surface. The Ag decorated MoO3 (Ag-MoO3)
      nanostructured sample shows enhanced field emission properties with an
      approimately 2.1 times lower turn-on voltage of 1.67 V MUm-1 and one order higher
      field enhancement factor (beta) of 8.6 * 104 compared to the MoO3 sample without
      Ag incorporation. From Kelvin probe force microscopy measurements, the average
      local work function (Phi) is found to be approximately 0.47 eV smaller for the Ag
      MoO3 sample (~5.70 +/- 0.05 eV) compared to the MoO3 sample (~6.17 +/- 0.05 eV)
      and the reduction in Phi can be attributed to the shifting Fermi level of MoO3
      toward vacuum via electron injection from Ag NPs to MoO3. The presence of oxygen
      vacancies together with Ag NPs lead to the highest beta and lowest turn-on field
      among the reported values under the MoO3 emitter category.

PMID- 28749377
TI  - Optical response in Weyl semimetal in model with gapped Dirac phase.
AB  - We study the optical properties of Weyl semimetal (WSM) in a model which
      features, in addition to the usual term describing isolated Dirac cones
      proportional to the Fermi velocity v F, a gap term m and a Zeeman spin-splitting
      term b with broken time reversal symmetry. Transport is treated within Kubo
      formalism and particular attention is payed to the modifications that result from
      a finite m and b. We consider how these modifications change when a finite
      residual scattering rate [Formula: see text] is included. For [Formula: see text]
      the A.C. conductivity as a function of photon energy [Formula: see text]
      continues to display the two quasilinear energy regions of the clean limit for
      [Formula: see text] below the onset of the second electronic band which is gapped
      at ([Formula: see text]). For [Formula: see text] of the order m little trace of
      two distinct linear energy scales remain and the optical response has evolved
      towards that for [Formula: see text]. Although some quantitative differences
      remain there are no qualitative differences. The magnitude of the D.C.
      conductivity [Formula: see text] at zero temperature ([Formula: see text]) and
      chemical potential ([Formula: see text]) is altered. While it remains
      proportional to [Formula: see text] it becomes inversely dependent on an
      effective Fermi velocity out of the Weyl nodes equal to [Formula: see text] which
      decreases strongly as the phase boundary between Weyl semimetal and gapped Dirac
      phase (GDSM) is approached at [Formula: see text]. The leading term in the
      approach to [Formula: see text] for finite [Formula: see text], [Formula: see
      text] and [Formula: see text] is found to be quadratic. The coefficient of these
      corrections tracks closely the [Formula: see text] dependence of the [Formula:
      see text] limit with differences largest near to the WSM-GDSM boundary.

PMID- 28749378
TI  - Compton scatter tomography in TOF-PET.
AB  - Scatter coincidences contain hidden information about the activity distribution
      on the positron emission tomography (PET) imaging system. However, in
      conventional reconstruction, the scattered data cause the blurring of images and
      thus are estimated and subtracted from detected coincidences. List mode format
      provides a new aspect to use time of flight (TOF) and energy information of each
      coincidence in the reconstruction process. In this study, a novel approach is
      proposed to reconstruct activity distribution using the scattered data in the PET
      system. For each single scattering coincidence, a scattering angle can be
      determined by the recorded energy of the detected photons, and then possible
      locations of scattering can be calculated based on the scattering angle. Geometry
      equations show that these sites lie on two arcs in 2D mode or the surface of a
      prolate spheroid in 3D mode, passing through the pair of detector elements. The
      proposed method uses a novel and flexible technique to estimate source origin
      locations from the possible scattering locations, using the TOF information.
      Evaluations were based on a Monte-Carlo simulation of uniform and non-uniform
      phantoms at different resolutions of time and detector energy. The results show
      that although the energy uncertainties deteriorate the image spatial resolution
      in the proposed method, the time resolution has more impact on image quality than
      the energy resolution. With progress of the TOF system, the reconstruction using
      the scattered data can be used in a complementary manner, or to improve image
      quality in the next generation of PET systems.

PMID- 28749379
TI  - Theoretical limits to sensitivity and resolution in magneto-acousto-electrical
      tomography.
AB  - In this study, the performance of magneto-acousto-electrical tomography (MAET) is
      investigated quantitatively by considering interrelations between its
      sensitivity, resolution and conductivity contrast. An analytical solution for the
      forward problem of MAET is derived for two-dimensional (2D) concentric bodies by
      the separation of variables method. The electric potential and the acoustic
      pressure are separated into their angular and radial components. The series
      coefficients for these solutions are obtained from their respective boundary
      conditions. The electric potential on the boundary is related to the acoustic
      boundary acceleration analytically. From this relation, a sensitivity expression
      is derived relating fractional change in conductivity contrast to fractional
      change in the measured electric potential. This expression is a function of the
      resolution and conductivity contrast of the imaging system. It also depends on
      the acoustic wave number and the dimensions of the body. The pair-wise relations
      between these parameters are presented. The sensitivity behavior of MAET is
      compared with applied current electrical impedance tomography and the
      improvements for small inhomogeneities are presented. For eccentric bodies, a
      modified expression for the sensitivity is obtained by conformal mapping. For
      arbitrary periodic boundary excitations, the sensitivity expressions for harmonic
      cases are combined to obtain a unified sensitivity expression.

PMID- 28749380
TI  - Handling interference effects on foraging with bucket brigades.
AB  - Many kinds of bio-inspired tasks have been tested with swarm robotics and task
      partitioning is one of the challenging subjects. In nature, it is well known that
      some colonies of social insects such as honeybees, termites, and ants use task
      partitioning strategies for their survival. In this paper, we demonstrate an
      effect of the task partitioning strategy called bucket brigade, which uses the
      direct transfer of materials or food between a pair of workers. We propose a task
      partitioning strategy based on the moving speeds of agents for the foraging task.
      We test various environmental conditions and compare the performance between task
      partitioning groups and non-partitioning groups. The experimental results show
      that task partitioning may not always be the best solution for foraging
      performance. However, when there exists a transfer bottleneck at a central
      location such as the entrance of the nest, task partitioning can be an effective
      strategy for reducing the traffic jam and improving the overall foraging
      performance of a group. The bucket brigade sequenced from the slowest agents
      (near the food source) to the fastest agents (near the nest) can particularly
      improve performance significantly in the region with traffic congestion near the
      nest. Generally, many social insect colonies consist of a number of members, and
      the entrances of colony nests always suffer from heavy traffic congestion. Our
      experimental results support the hypothesis that several social insects use one
      of the task partitioning strategies based on bucket brigades in their foraging
      tasks.

PMID- 28749381
TI  - Cutaneous malakoplakia: Interesting case report and review of literature.

PMID- 28749382
TI  - Image manipulation and image plagiarism - what's fine and what's not?

PMID- 28749383
TI  - A noncancerous variant of xeroderma pigmentosum type D associated with novel
      heterozygous missense ERCC2 gene mutation.

PMID- 28749384
TI  - Partial dysautonomia: An interesting presentation.

PMID- 28749385
TI  - Demodex folliculorum associated Bacillus pumilus in lesional areas in rosacea.

PMID- 28749386
TI  - Epidermolysis bullosa acquisita and anti-p200 pemphigoid as major subepidermal
      autoimmune bullous diseases diagnosed by floor binding on indirect
      immunofluorescence microscopy using human salt-split skin.
AB  - BACKGROUND: Subepidermal autoimmune bullous diseases are a diverse group of
      diseases with overlapping clinical and immunopathological features. Indirect
      immunofluorescence microscopy on artificially split skin helps to classify these
      conditions into those with staining on the epidermal side of the split ("roof
      binding") and those with staining on the dermal side ("floor-binding").
      Epidermolysis bullosa acquisita is the prototype of "floor-binding" subepidermal
      autoimmune bullous diseases. However, not all floor-binding sera are associated
      with epidermolysis bullosa acquisita. AIM: The aim of this study was to evaluate
      the clinical and immunological profile of patients with floor-binding
      subepidermal autoimmune bullous disease by indirect immunofluorescence microscopy
      and to identify the target antigens in them. METHODS: Ten patients who showed a
      floor-binding pattern were studied with regard to their clinical and
      immunopathological characteristics. Target antigens were identified by modified
      indirect immunofluorescence microscopy using recessive dystrophic epidermolysis
      bullosa skin, enzyme linked immunosorbent assay, and immunoblotting. RESULTS:
      Diagnosis of epidermolysis bullosa acquisita was confirmed in six patients. Three
      patients with an inflammatory subepidermal autoimmune bullous disease mimicking
      bullous pemphigoid reacted with a 200 kDa protein on immunoblotting with dermal
      extract, as is characteristic of anti-p200 pemphigoid. One serum showed both roof
      and floor binding, and reacted with the BP180 antigen. LIMITATION: We could not
      perform serration pattern analysis in our patients. CONCLUSION: In this study, we
      report three cases of anti-p200 pemphigoid from India. These cases, though
      indistinguishable clinically from bullous pemphigoid, revealed a floor-binding
      pattern on indirect immunofluorescence using salt-split skin.

PMID- 28749387
TI  - A new free-cost e-service supporting clinicians to manage their difficult-to
      treat tuberculosis cases: The European Respiratory Society-World Health
      Organization tuberculosis Consilium.

PMID- 28749388
TI  - Playing soft, with tough players: Controlling adverse drug effects while tuning
      antiepileptic drugs, epilepsy & the person.

PMID- 28749389
TI  - Starting the conversation - Integrating mental health into maternal health care
      in India.

PMID- 28749390
TI  - Extensively drug-resistant tuberculosis in India: Current evidence on diagnosis &
      management.
AB  - Emergence of extensively drug-resistant tuberculosis (XDR-TB) has significantly
      threatened to jeopardize global efforts to control TB, especially in HIV endemic
      regions. XDR-TB is mainly an iatrogenically created issue, and understanding the
      epidemiological and risk factors associated with it is of paramount importance in
      curbing this menace. Emergence of this deadly phenomenon can be prevented by
      prompt diagnosis and effective treatment with second-line drugs in rifampicin
      resistant TB (RR-TB) as well as multidrug-resistant TB (MDR-TB) patients. Optimal
      treatment of RR-TB, MDR-TB and XDR-TB cases alone will not suffice to reduce the
      global burden. The TB control programmes need to prioritize on policies focusing
      on the effective as well as rational use of first-line drugs in every newly
      diagnosed drug susceptible TB patients so as to prevent the emergence of drug
      resistance.

PMID- 28749391
TI  - Variations in herpes zoster manifestation.
AB  - Herpes zoster (HZ) is a neurocutaneous disorder due to endogenous reactivation of
      the varicella-zoster virus (VZV). The typical clinical manifestation is an acute
      segmental eruption of herpetiform umbilicated vesicles associated with malaise,
      pain, dysaesthesia, allodynia and probably fever. This review focuses on other
      possible clinical manifestations of the disease to sensitize physicians not to
      overlook HZ since only an early antiviral treatment can reduce the risk of post
      zosteric neuralgia.

PMID- 28749392
TI  - Evaluation of evidence for pharmacokinetics-pharmacodynamics-based dose
      optimization of antimicrobials for treating Gram-negative infections in neonates.
AB  - BACKGROUND & OBJECTIVES: Neonates present a special subgroup of population in
      whom optimization of antimicrobial dosing can be particularly challenging. Gram
      negative infections are common in neonates, and inpatient treatment along with
      critical care is needed for the management of these infections. Dosing
      recommendations are often extrapolated from evidence generated in older patient
      populations. This systematic review was done to identify the knowledge gaps in
      the pharmacokinetics-pharmacodynamics (PK-PD)-based optimized dosing schedule for
      parenteral antimicrobials for Gram-negative neonatal infections. METHODS:
      Relevant research questions were identified. An extensive electronic and manual
      search methodology was used. Potentially eligible articles were screened for
      eligibility. The relevant data were extracted independently in a pre-specified
      data extraction form. Pooling of data was planned. RESULTS: Of the 340 records
      screened, 24 studies were included for data extraction and incorporation in the
      review [carbapenems - imipenem and meropenem (n=7); aminoglycosides - amikacin
      and gentamicin (n=9); piperacillin-tazobactam (n=2); quinolones (n=2); third- and
      fourth-generation cephalosporins (n=4) and colistin nil]. For each of the drug
      categories, the information for all the questions that the review sought to
      answer was incomplete. There was a wide variability in the covariates assessed,
      and pooling of results could not be undertaken. INTERPRETATION & CONCLUSIONS:
      There is a wide knowledge gap for determining the doses of antimicrobials used
      for Gram-negative infections in neonates. A different profile of newborns in the
      developing countries could affect the disposition of antimicrobials for Gram
      negative infections, necessitating the generation of PK-PD data of antimicrobials
      in neonates from developing countries. Further, guidelines for treatment of
      neonatal conditions may incorporate the evidence-based PK-PD-guided dosing
      regimens.

PMID- 28749393
TI  - Adverse effects & drug load of antiepileptic drugs in patients with epilepsy:
      Monotherapy versus polytherapy.
AB  - BACKGROUND & OBJECTIVES: Although the need for a combination of antiepileptic
      drugs (AEDs) in the treatment of epilepsy is well justified, but an associated
      increase in adverse effects (AEs) lends a restriction to polytherapy. The aim of
      this study was to evaluate AEs and drug load (prescribed daily dose/defined daily
      doses) of AEDs in patients with epilepsy (PWE). METHODS: Consecutive PWEs
      attending Epilepsy clinic in a tertiary care hospital in New Delhi, India, were
      enrolled in the study. Demographic variables, such as age, gender, diagnosis, age
      at onset of seizures, frequency of seizures, use of all AEDs and adverse event
      profile (AEP) score were noted. Routine laboratory tests including lipid profile,
      fasting blood glucose, haematological parameters and liver and kidney function
      tests were done. RESULTS: A total of 697 consecutive patients were included in
      this study. Of them, 64.4 per cent were male; mean age was 29.6 +/- 10.6 yr.
      Generalized seizures and focal seizures were recorded in n=386 (55.4%) and n=311
      (44.6%), respectively. Monotherapy and polytherapy with two and greater than or
      equal to three AEDs were prescribed in 264 (37.9%), 243 (34.9%) and 190 (27.2%)
      patients, respectively. The average AED load, duration of treatment as well as
      AEP score were found to be significantly higher in combination of greater than or
      equal to three AEDs as compared to both monotherapy and combination of two AEDs,
      whereas no significant difference was observed between monotherapy and
      combination of two AEDs. Patients on monotherapy were in good control of seizures
      as compared to polytherapy. There was no significant change in biochemical
      parameters between the groups. INTERPRETATION & CONCLUSIONS: Polytherapy with
      combination of greater than or equal to three AEDs was associated with higher AEs
      and lower seizure control as compared to both monotherapy and combination of two
      AEDs. AEs did not correlate with AED load, seizure type, gender and age of the
      patients but were associated with both numbers of AEDs as well as seizure
      frequency in PWE.

PMID- 28749394
TI  - Serum levels of soluble urokinase plasminogen activator receptor as a new
      inflammatory marker in adolescent obesity.
AB  - BACKGROUND & OBJECTIVES: Obesity is known for low-grade inflammatory state with
      enhanced production of inflammatory mediators in children and adolescents.
      Soluble urokinase plasminogen activator receptor (suPAR) can be generated as a
      pro-inflammatory marker. This study was conducted to evaluate the role of suPAR,
      and its association with leptin, adiponectin, interleukin-6 (IL-6), high
      sensitive C-reactive protein (hsCRP) and fibrinogen in adolescent obesity.
      METHODS: A total of 98 participants, 55 obese individuals and 43 healthy
      controls, aged between 10 and 17 yr, were included in the study. Serum suPAR, IL
      6, leptin and adiponectin were measured using ELISA method. RESULTS: Serum suPAR,
      IL-6, fibrinogen, hsCRP and leptin levels in obese individuals were significantly
      higher than those of controls (P<0.05 & P<0.001). Serum adiponectin levels in
      obese individuals were significantly lower than those of controls (P<0.01).
      INTERPRETATION & CONCLUSIONS: Our findings showed that suPAR, IL-6, fibrinogen,
      hsCRP and leptin were significantly higher in the obese individuals than those of
      controls. suPAR may be a good novel biomarker for systemic subclinical
      inflammation and immune activation linked to adolescent obesity.

PMID- 28749395
TI  - Comparative study of clinical features of patients with celiac disease & those
      with concurrent celiac disease & type 1 diabetes mellitus.
AB  - BACKGROUND & OBJECTIVES: Celiac disease (CD) and type 1 diabetes mellitus (T1DM)
      share a common genetic locus and clinical manifestations. The present study was
      planned to compare clinical, biochemical and hormonal profiles of patients with
      CD and CD with T1DM. METHODS: Records of CD patients with age <=20 yr, available
      anthropometric measurements, haematological, biochemical and hormonal workup with
      tissue transglutaminase IgA antibody and duodenal biopsy (Marsh grade) were
      screened. The patients were divided into two groups i.e., CD alone (Group A) and
      concurrent CD with T1DM (Group B). RESULTS: One hundred and nine patients of CD
      (57 male) with a mean age of 14.9+/-2.9 yr were evaluated. Of these, 86 (78.9%)
      patients had CD alone and 23 (13 females) (21.1%) patients had CD with T1DM. The
      age at diagnosis and the lag duration for the diagnosis of CD were 11.5+/-4.6
      versus 13.8+/-3.4 yr (P<0.05) and 48.8 +/-43.3 versus 20.2+/-31.8 months (P<0.05)
      in groups A and B, respectively. The most common histopathological grade was type
      3b (59.2%) in group A and type 2 (42.1%) in group B. Short stature (87% vs.
      40.9%; P<0.01), anaemia (80.9% vs. 45%, P<0.01) and delayed puberty (61.9% vs.
      29.4%; P<0.01) were more common in group A. INTERPRETATION & CONCLUSIONS:
      Patients with CD alone have a longer lag time to diagnosis and consequent sequel
      in the form of anaemia, short stature and delayed puberty, as compared to
      patients with concurrent CD and T1DM.

PMID- 28749396
TI  - Validity of Broselow tape for estimating weight of Indian children.
AB  - BACKGROUND & OBJECTIVES: The Broselow tape has been validated in both ambulatory
      and simulated emergency situations in the United States and is believed to reduce
      complications arising from inaccurate drug dosing and equipment sizing in
      paediatric population. This study was conducted to determine the relationship
      between the actual weight and weight determined by Broselow tape in the Indian
      children and to derive an equation for determination of weight based on height in
      the Indian children. METHODS: This cross-sectional study was conducted at a
      tertiary care hospital in Mumbai, India. The participants' weights were divided
      into three groups <10 kg, 10-18 kg and >18 kg with a total sample size estimated
      to be 210 (70 in each group). Using the tape, the measured weight was compared to
      Broselow-predicted weight and percentage weight was calculated. Accuracy was
      defined as agreement on Broselow colour-coded zones, as well as agreement within
      10 per cent between the measured and Broselow-predicted weights. The resulting
      data were compared with weights estimated by advanced paediatric life support
      (APLS) and updated APLS formulae using Pearson's correlation coefficient.
      RESULTS: The mean percentage differences were -11.78, -17.09 and -14.27 per cent
      for <10, 10-18 and >18 kg weight-based groups, respectively. The Broselow colour
      coded zone agreement was 33.3 per cent in children weighing <10 kg, but only 7.4
      per cent in the 10-18 kg group and 33.9 per cent in the >18 kg group. Agreement
      within 10 per cent was 53.13 per cent for the <10 kg group, but only 21.08 per
      cent for the 10-18 kg group and 33.9 per cent for the >18 kg group. Application
      of 10 per cent weight correction factor improved the percentages to 79.2 per cent
      for the <10 kg category, to 55.70 per cent for the 10-18 kg group and to 61.0 per
      cent for the >18 kg group. The correlation coefficient between actual weight and
      weights estimated by Broselow tape (r=0.89) was higher than that between actual
      weight and weight estimated by APLS method or updated APLS formulae (r=0.68) in
      12-60 months age group as well as in >60 months age group (r=0.76).
      INTERPRETATION & CONCLUSIONS: Broselow weight overestimated weight by >10 per
      cent in majority of Indian children. The weight overestimation was greater in
      children belonging to over 18 and 10-18 kg weight groups. Applying 10 per cent
      weight correction factor to the Broselow-predicted weight may provide a more
      accurate estimation of actual weight in children attending public hospital.
      Weights estimated using Broselow tape correlated better with actual weights than
      those calculated using APLS and updated APLS formulae.

PMID- 28749397
TI  - Action-oriented colour-coded foot length calliper for primary healthcare workers
      as a proxy for birth weight & gestational period.
AB  - BACKGROUND & OBJECTIVES: Foot length of the newborn has a good correlation with
      the birth weight and is recommended to be used as a proxy measure. There can be
      variations in the measurement of foot length. A study was, therefore, carried out
      to develop a foot length calliper for accurate foot length measurement and to
      find cut-off values for birth weight and gestational age groups to be used by
      primary healthcare workers. METHODS: This study was undertaken on 645 apparently
      healthy newborn infants with known gestational age. Nude birth weight was taken
      within 24 h of birth on a standard electronic weighing machine. A foot length
      calliper was developed. Correlation between foot length and birth weight as well
      as gestational age was calculated. Correctness of cut-off values was tested using
      another set of 133 observations on the apparently healthy newborns. Action
      oriented colour coding was done to make it easy for primary healthcare workers to
      use it. RESULTS: There was a significant correlation of foot length with birth
      weight (r=0.75) and gestational age (r=0.63). Cut-off values for birth weight
      groups were 6.1, 6.8 and 7.3 cm and for gestational age of 6.1, 6.8 and 7.0 cm.
      Correctness of these cut-off values ranged between 77.1 and 95.7 per cent for
      birth weight and 60-93.3 per cent for gestational age. Considering 2.5 kg as cut
      off between normal birth weight and low birth weight (LBW), cut-off values of
      6.1, 6.8 and 7.3 were chosen. Action-oriented colour coding was done by
      superimposing the colours on the scale of the calliper, green indicating home
      care, yellow indicating supervised home care, orange indicating care at newborn
      care units at primary health centres and red indicating Neonatal Intensive Care
      Unit care for infants. INTERPRETATION & CONCLUSIONS: A simple device was
      developed so that the primary health care workers and trained Accredited Social
      Health Activist workers can identify the risk of LBW in the absence of accurate
      weighing facilities and decide on the type of care needed by the newborn and take
      action accordingly.

PMID- 28749398
TI  - F wave index: A diagnostic tool for peripheral neuropathy.
AB  - BACKGROUND & OBJECTIVES: Each skeletal muscle is usually supplied by two or more
      nerve roots and if one nerve root is affected and the other is spared, the
      clinically used F wave minimum latency can still be normal. An F wave index was
      constructed taking into consideration the other parameters of the F wave such as
      persistence, chronodispersion, latency, arm-length to determine its usefulness in
      the diagnosis of peripheral neuropathy. This study was undertaken to construct
      the F wave index in the upper limb for the median nerve in normal healthy adult
      males and in patients with peripheral neuropathy and to compare the values
      obtained in both groups. METHODS: This hospital-based study was carried out on 40
      males who were diagnosed to have peripheral neuropathy and on 40 age matched
      healthy males who served as the control group. The F wave recording was done
      using a digitalized nerve conduction/electromyography/EP machine in a quiet and
      dimly lit room. All recordings were done between 0900 and 1100 h at an ambient
      temperature of 22 degrees C. The F wave recording was obtained from a fully
      relaxed muscle by stimulating the median nerve. RESULTS: The median value for F
      wave index obtained from median nerve (abductor pollicis brevis) in patients with
      peripheral neuropathy [right arm - 35.85, interquartile range (IQR) - 35.26; left
      arm - 39.49, IQR - 39.49] was significantly lower (P=0.001) as compared to the
      control group (right arm - 102.62, IQR - 83.76; left arm - 77.43, IQR - 58.02).
      INTERPRETATION & CONCLUSIONS: Our results showed that F wave index in upper limb
      was significantly lower in patients with peripheral neuropathy than the healthy
      controls, and could be used for early detection of peripheral neuropathy.

PMID- 28749399
TI  - Re-establishment of normal radioactive iodine uptake reference range in the era
      of universal salt iodization in the Indian population.
AB  - BACKGROUND & OBJECTIVES: The reference radioactive iodine uptake (RAIU) values
      established in the 1970s in the era of widespread iodine deficiency were
      relatively high. Now, after four decades of successful Universal Salt Iodization
      (USI) programme in India, there is a need to re-establish these reference ranges.
      The present study was aimed to quantify the two-hour and 24-h RAIU values in
      iodine sufficient euthyroid individuals and validate the results in Graves' and
      Hashimoto's thyroiditis patients. METHODS: In this prospective study conducted
      from April 2012 to September 2013, euthyroid volunteers who consented for the
      investigations were enrolled in the study. Treatment-naive Graves' disease and
      Hashimoto's thyroiditis patients were recruited from the outpatient clinic. The
      investigations included neck ultrasonography, thyroid function tests,
      thyroglobulin (Tg), anti-Tg and anti-thyroid peroxidase antibody and urinary
      iodine concentration. RESULTS: Three different groups comprising 110 euthyroid
      volunteers, 38 Graves' and 17 Hashimoto's thyroiditis patients were enrolled in
      the study. The mean 2-h RAIU values for the euthyroid group, Hashimoto's
      thyroiditis and Graves' patients were 3.83+/-2.77, 4.22+/-3.41 and 32.67+/-15.93
      per cent, and mean 24-h RAIU values were 12.75+/-5.51, 11.66+/-9.55 and 61.85+/
      12.9 per cent, respectively. The mean thyroid volumes were 7.63+/-2.72, 7.81+/
      1.67 and 20.76+/-12.56 ml for the euthyroid, Hashimoto's thyroiditis and Graves'
      disease groups and the mean spot urinary iodine concentrations were 9.0, 7.8 and
      13.9 MUg/dl in the three groups, respectively. The new reference range (95%
      confidence interval) for two-hour was 1-7 per cent and 24-h was 7-18 per cent.
      INTERPRETATION & CONCLUSIONS: Compared to the previous values, there was a
      considerable decrease in the RAIU values in euthyroid individuals. This was
      further corroborated with increase in the urinary iodine concentration and
      decrease in thyroid volume, attributed to successful USI programme. Further
      studies with a large sample from different parts of India need to be done to
      confirm these findings.

PMID- 28749400
TI  - A novel approach for characterizing variations in serum peptides in rheumatic
      heart disease.
AB  - BACKGROUND & OBJECTIVES: Acute rheumatic fever and rheumatic heart disease (RHD)
      are important public health problems in developing countries. In this study,
      peptidomic analyses on RHD patients and healthy individuals were performed to
      characterize variations in serum peptide levels using label-free quantitation
      approaches. METHODS: Blood samples were obtained from 160 healthy controls and
      160 RHD patients. Of the 448 identified peptides, 272 were analyzed by two label
      free mass spectrometry methods, the spectral count and spectral index. RESULTS:
      There were 38 proteins and 95 peptides with significant (adjusted P<0.001)
      differences in the abundance of peptides between healthy controls and RHD
      patients, including multiple peptides derived from histone H2B, villin-like
      protein, complement C4-B and motile sperm domain containing protein-2. The levels
      of 10 peptides were upregulated, and 85 peptides were downregulated in patients
      compared to controls. In addition, in patients, the levels of four proteins were
      upregulated and 34 were downregulated compared to controls. INTERPRETATION &
      CONCLUSIONS: This study shows that detection of significant changes in serum
      peptides reflects the difference between RHD patients and healthy controls. This
      label-free method may be helpful for clinicians to treat RHD patients during the
      perioperative period.

PMID- 28749401
TI  - Use of real-time ultrasound for locating tip position in neonates undergoing
      peripherally inserted central catheter insertion: A pilot study.
AB  - BACKGROUND & OBJECTIVES: Securing long-term venous access is an essential part of
      sick newborn care. The malposition of central line tip leads to several
      complications. There is a need for an easily available bedside investigating tool
      to diagnose these malpositions. This study was done to compare the effectiveness
      of real-time ultrasound (RTUS) with X-ray in identifying the peripherally
      inserted central catheter (PICC) line tip. METHODS: This pilot observational
      study was conducted in a level III Neonatal Intensive Care Unit of a tertiary
      care hospital in India, from June 2012 to June 2013. A total of 33 PICC lines in
      31 infants were included in the study. After insertion of PICC line, X-ray and
      RTUS were done to locate the tip of the PICC line. RESULTS: In this study, PICC
      line tip could be identified by bedside RTUS in 94 per cent of line insertions.
      Standard X-ray identified the tip in all cases. RTUS has been shown to have good
      diagnostic utility in comparison with X-ray with sensitivity and specificity
      being 96.55 and 100 per cent, respectively. In our study, majority of
      malpositions were identified and manipulated by RTUS, thus second X-rays were
      avoided. INTERPRETATION & CONCLUSIONS: The result of this pilot study shows that
      RTUS may be a reliable and safe bedside tool for determining the tip of PICC
      lines. However, studies with large sample size need to be done to confirm these
      findings.

PMID- 28749402
TI  - Coverage of childhood vaccination among children aged 12-23 months, Tamil Nadu,
      2015, India.
AB  - BACKGROUND & OBJECTIVES: District-Level Household Survey-4 (DLHS-4) indicated
      that during 2012-2013, only 56 per cent of children aged 12-23 months in Tamil
      Nadu were fully vaccinated, which were lesser than those reported in earlier
      national surveys. We, therefore, conducted cluster surveys to estimate coverage
      of childhood vaccination in the State, and also to identify the factors
      associated with low coverage. METHODS: Cross-sectional surveys were conducted in
      15 strata [municipal corporation non-slum (n=1), municipal corporation slum
      (n=1), hilly (n=1), rural (n=6) and urban (n=6)]. From each stratum, 30 clusters
      were selected using probability proportional to the population size linear
      systematic sampling; seven children aged 12-23 months were selected from each
      cluster and their mothers/care-takers were interviewed to collect information
      about vaccination status of the child. A child was considered fully vaccinated if
      he/she received bacillus Calmette-Guerin (BCG), three doses of pentavalent, three
      doses of oral polio vaccine and one dose of measles vaccine, and appropriately
      vaccinated if all vaccine doses were given at right age and with right interval.
      Further, coverage of fully vaccinated children (FVC) as per vaccination cards or
      mothers' recall, validated coverage of FVC (V-FVC) among those having cards, and
      coverage of appropriately vaccinated children (AVC) were estimated using survey
      data analysis module with appropriate sampling weights. RESULTS: A total of 3150
      children were surveyed, of them 2528 (80.3%) had vaccination card. The weighted
      coverage of FVC, V-FVC and AVC in the State was 79.9 per cent [95% confidence
      interval (CI): 78.2-81.5], 78.8 per cent (95% CI: 76.9-80.5) and 69.7 per cent
      (95% CI: 67.7-71.7), respectively. The coverage of individual vaccine ranged
      between 84 per cent (measles) and 99.8 per cent (BCG). About 12 per cent V-FVC
      were not vaccinated as per the vaccination schedule. INTERPRETATION &
      CONCLUSIONS: The coverage of FVC in Tamil Nadu was high, with about 80 per cent
      children completing primary vaccination. Efforts to increase vaccination coverage
      in the State need to focus on educating vaccinators about the need to adhere to
      the national vaccination schedule and strengthening supervision to ensure that
      children are vaccinated appropriately.

PMID- 28749403
TI  - HIV-malaria interactions in North-East India: A prospective cohort study.
AB  - BACKGROUND & OBJECTIVES: The interactions between HIV and malaria co-infection
      have been shown to influence each other in their clinical outcomes in Sub-Saharan
      Africa. This study was carried out in the two States of north east India endemic
      for both HIV and malaria infections, to study the interactions between the two
      diseases in the HIV-infected population. METHODS: In this prospective study, a
      total of 333 HIV-infected individuals were followed up for a period of 6-18
      months in Mizoram and Manipur during 2010-2011. The study assessed the changes in
      viral load and also the therapeutic efficacy of artesunate plus sulphadoxine
      pyrimethamine (AS+SP) combination therapy in HIV-infected and HIV-uninfected
      individuals with Plasmodium falciparum malaria. RESULTS: Viral load in HIV
      infected malaria patients on day zero (D0) ranged from 1110 to 147,000 copies/ml.
      The log transformation of the geometric means of HIV viral loads revealed no
      significant difference on different days of follow up. There was 100 per cent
      adequate clinical and parasitological response (ACPR) after treating with
      artemisinin based combination therapy (ACT) both in HIV-infected and HIV
      uninfected P. falciparum-positive individuals. Similarly, chloroquine showed 100
      per cent ACPR in P. vivax HIV-infected individuals. INTERPRETATION & CONCLUSION:
      The study showed no significant increase in HIV viral load in malaria cases. All
      HIV-infected and HIV-uninfected P. falciparum malaria-positive cases responded to
      the treatment with 100 per cent ACPR.

PMID- 28749404
TI  - Role of NEUT-X & NEUT-Y in picking up megaloblastic anaemia on peripheral blood &
      in differentiating from other macrocytic anaemia.

PMID- 28749405
TI  - Malaria-associated secondary haemophagocytic lymphohistiocytosis: Report of two
      cases & a review of literature.

PMID- 28749406
TI  - A rare case of maxillary artery aneurysm.

PMID- 28749407
TI  - Multi-Robot Interfaces and Operator Situational Awareness: Study of the Impact of
      Immersion and Prediction.
AB  - Multi-robot missions are a challenge for operators in terms of workload and
      situational awareness. These operators have to receive data from the robots,
      extract information, understand the situation properly, make decisions, generate
      the adequate commands, and send them to the robots. The consequences of excessive
      workload and lack of awareness can vary from inefficiencies to accidents. This
      work focuses on the study of future operator interfaces of multi-robot systems,
      taking into account relevant issues such as multimodal interactions, immersive
      devices, predictive capabilities and adaptive displays. Specifically, four
      interfaces have been designed and developed: a conventional, a predictive
      conventional, a virtual reality and a predictive virtual reality interface. The
      four interfaces have been validated by the performance of twenty-four operators
      that supervised eight multi-robot missions of fire surveillance and
      extinguishing. The results of the workload and situational awareness tests show
      that virtual reality improves the situational awareness without increasing the
      workload of operators, whereas the effects of predictive components are not
      significant and depend on their implementation.

PMID- 28749408
TI  - Clinical Role of ASCT2 (SLC1A5) in KRAS-Mutated Colorectal Cancer.
AB  - Mutation in the KRAS gene induces prominent metabolic changes. We have recently
      reported that KRAS mutations in colorectal cancer (CRC) cause alterations in
      amino acid metabolism. However, it remains to be investigated which amino acid
      transporter can be regulated by mutated KRAS in CRC. Here, we performed a
      screening of amino acid transporters using quantitative reverse-transcription
      polymerase chain reaction (RT-PCR) and then identified that ASCT2 (SLC1A5) was up
      regulated through KRAS signaling. Next, immunohistochemical analysis of 93
      primary CRC specimens revealed that there was a significant correlation between
      KRAS mutational status and ASCT2 expression. In addition, the expression level of
      ASCT2 was significantly associated with tumor depth and vascular invasion in KRAS
      mutant CRC. Notably, significant growth suppression and elevated apoptosis were
      observed in KRAS-mutant CRC cells upon SLC1A5-knockdown. ASCT2 is generally known
      to be a glutamine transporter. Interestingly, SLC1A5-knockdown exhibited a more
      suppressive effect on cell growth than glutamine depletion. Furthermore, SLC1A5
      knockdown also resulted in the suppression of cell migration. These results
      indicated that ASCT2 (SLC1A5) could be a novel therapeutic target against KRAS
      mutant CRC.

PMID- 28749409
TI  - Host Response Comparison of H1N1- and H5N1-Infected Mice Identifies Two Potential
      Death Mechanisms.
AB  - Highly pathogenic influenza A viruses (IAV) infections represent a serious threat
      to humans due to their considerable morbidity and mortality capacities. A good
      understanding of the molecular mechanisms responsible for the acute lung injury
      observed during this kind of infection is essential to design adapted therapies.
      In the current study, using an unbiased transcriptomic approach, we compared the
      host-responses of mice infected with two different subtypes of IAV: H1N1 vs.
      H5N1. The host-response comparison demonstrated a clear difference between the
      transcriptomic profiles of H1N1- and H5N1-infected mice despite identical
      survival kinetics and similar viral replications. The ontological analysis of the
      two transcriptomes showed two probable causes of death: induction of an
      immunopathological state of the lung for the H1N1 strain vs. development of
      respiratory dysfunction in the case of the H5N1 IAV. Finally, a clear signature
      responsible for lung edema was specifically associated with the H5N1 infection.
      We propose a potential mechanism of edema development based on predictive
      bioinformatics tools.

PMID- 28749410
TI  - Awareness of the Risk of Exposure to Infectious Material and the Behaviors of
      Polish Paramedics with Respect to the Hazards from Blood-Borne Pathogens-A
      Nationwide Study.
AB  - (1) Background: To determine paramedics' frequency of contact with blood and
      other body fluids, as well as the analysis of knowledge of paramedics about blood
      borne infections, their attitudes to patients infected with blood-borne viruses,
      and the post-exposure procedures implemented by paramedics; (2) Methods: An
      anonymous questionnaire among 190 paramedics working in various health care
      facilities in Poland (adjusted response rate, 76.3%); (3) Results: 78% of
      paramedics had contact with potentially infectious material at least several
      times a week. Paramedics' knowledge on transferring infection was insufficient.
      Paramedics with longer employment time and better professional experience
      suffered fewer injuries with used needles/medical tools (p = 0.079). Most
      frequently reported factors that prevented the use of personal protective
      equipment were emergency situations (19.5%), skin irritations and contact
      allergies (19%) and, in the case of protective gloves, reduced manual dexterity
      (16%). In total, 82% of paramedics were concerned about the risk of being
      infected with HIV, HBV or HCV as a result of performing their job. In total, 97%
      of paramedics behaved more carefully while caring for infected patients. In
      total, 90% of the paramedics never refrained from performing the specific
      procedures necessary to help the patient whom they knew to be infected; (4)
      Conclusions: Despite the paramedics' insufficient theoretical knowledge about the
      risk of blood-borne infections, the emphasis in the training of future paramedics
      should be on classes perfecting practical skills, because growing experience
      significantly reduces the risk of injury.

PMID- 28749411
TI  - Advances in Testing Techniques for Digital Microfluidic Biochips.
AB  - With the advancement of digital microfluidics technology, applications such as on
      chip DNA analysis, point of care diagnosis and automated drug discovery are
      common nowadays. The use of Digital Microfluidics Biochips (DMFBs) in disease
      assessment and recognition of target molecules had become popular during the past
      few years. The reliability of these DMFBs is crucial when they are used in
      various medical applications. Errors found in these biochips are mainly due to
      the defects developed during droplet manipulation, chip degradation and
      inaccuracies in the bio-assay experiments. The recently proposed Micro-electrode
      dot Array (MEDA)-based DMFBs involve both fluidic and electronic domains in the
      micro-electrode cell. Thus, the testing techniques for these biochips should be
      revised in order to ensure proper functionality. This paper describes recent
      advances in the testing technologies for digital microfluidics biochips, which
      would serve as a useful platform for developing revised/new testing techniques
      for MEDA-based biochips. Therefore, the relevancy of these techniques with
      respect to testing of MEDA-based biochips is analyzed in order to exploit the
      full potential of these biochips.

PMID- 28749412
TI  - Multi-Targeting Andrographolide, a Novel NF-kappaB Inhibitor, as a Potential
      Therapeutic Agent for Stroke.
AB  - A key focus in the field of drug discovery has been motivated by the
      neuroprotection of natural compounds. Cerebral ischemia is a multifaceted
      pathological process with a series of mechanisms, and a perspective for the
      development of neuroprotectants from traditional herbal medicine or natural
      products is a promising treatment for this disease. Natural compounds with the
      effects of anti-oxidation, anti-inflammation, anti-apoptosis, and neurofunctional
      regulation exhibit therapeutic effects on experimental ischemic brain injury.
      Conferring to the pharmacological mechanisms underlying neuroprotection, a study
      found that androgapholide, a diterpene lactone compound, exhibits varying degrees
      of neuroprotective activities in both in vitro and in vivo experimental models of
      stroke. The neuroprotective mechanisms of andrographolide are suggested as: (I)
      increasing nuclear factor E2-related factor 2-heme oxygenase (Nrf2-HO-1)
      expression through p38-mitogen activated protein kinase (MAPK) regulation, (II)
      inducing cerebral endothelial cells (CEC) apoptosis and caspase-3 activation,
      (III) down regulating Bax, inducible nitric oxide synthase (iNOS), and (IV)
      inhibiting hydroxyl radical (OH-) formation, and activating transcription factor
      NF-kappaB signaling pathways. Recently, several researchers have also been trying
      to unveil the principal mechanisms involved in the neuroprotective effects of
      andrographolide. Therefore, this review aims to summarize an overview on the
      neuroprotective effects of andrographolide and exemplifies the essential
      mechanisms involved. This paper can provide information that andrographolide drug
      discovery may be a promising strategy for the development of a novel class of
      neuroprotective drug.

PMID- 28749413
TI  - PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process.
AB  - During the proliferation and metastasis, the tumor cells prefer glycolysis
      (Warburg effect), but its exact mechanism remains largely unknown. In this study,
      we demonstrated that phosphoglycerate kinase 1 (PGK1) is an important enzyme in
      the pathway of metabolic glycolysis. We observed a significant overexpression of
      PGK1 in hepatocellular carcinoma tissues, and a correlation between PGK1
      expression and poor survival of hepatocellular carcinoma patients. Also, the
      depletion of PGK1 dramatically reduced cancer cell proliferation and metastasis,
      indicating an oncogenic role of PGK1 in liver cancer progression. Further
      experiments showed that PGK1 played an important role in MYC-induced metabolic
      reprogramming, which led to an enhanced Warburg effect. Our results revealed a
      new effect of PGK1, which can provide a new treatment strategy for hepatocellular
      carcinoma, as PGK1 is used to indicate the prognosis of hepatocellular carcinoma
      (HCC).

PMID- 28749414
TI  - Adjuvantation of Pulmonary-Administered Influenza Vaccine with GPI-0100 Primarily
      Stimulates Antibody Production and Memory B Cell Proliferation.
AB  - Adjuvants are key components in vaccines, they help in reducing the required
      antigen dose but also modulate the phenotype of the induced immune response. We
      previously showed that GPI-0100, a saponin-derived adjuvant, enhances antigen
      specific mucosal and systemic antibody responses to influenza subunit and whole
      inactivated influenza virus (WIV) vaccine administered via the pulmonary route.
      However, the impact of the GPI-0100 dose on immune stimulation and the immune
      mechanisms stimulated by GPI-0100 along with antigen are poorly understood.
      Therefore, in this study we immunized C57BL/6 mice via the pulmonary route with
      vaccine consisting of WIV combined with increasing amounts of GPI-0100,
      formulated as a dry powder. Adjuvantation of WIV enhanced influenza-specific
      mucosal and systemic immune responses, with intermediate doses of 5 and 7.5 MUg
      GPI-0100 being most effective. The predominant antibody subtype induced by GPI
      0100-adjuvanted vaccine was IgG1. Compared to non-adjuvanted vaccine, GPI-0100
      adjuvanted WIV vaccine gave rise to higher numbers of antigen-specific IgA- but
      not IgG-producing B cells in the lungs along with better mucosal and systemic
      memory B cell responses. The GPI-0100 dose was negatively correlated with the
      number of influenza-specific IFNgamma- and IL17-producing T cells and positively
      correlated with the number of IL4-producing T cells observed after immunization
      and challenge. Overall, our results show that adjuvantation of pulmonary
      delivered WIV with GPI-0100 mostly affects B cell responses and effectively
      induces B cell memory.

PMID- 28749415
TI  - Association between Toenail Magnesium and Type 2 Diabetes in Chinese Adults.
AB  - Previous studies have showed an inverse association between magnesium level and
      type 2 diabetes, but the results are inconsistent, and the evidence relates only
      to dietary and serum magnesium. Moreover, it is not certain how these findings
      are applicable to Asian people. This study was designed to examine the
      association between toenail magnesium and type 2 diabetes in Chinese adults. The
      sample was 5683 adults aged 18 years or older from the 2009 China Health and
      Nutrition Survey. We used hemoglobin A1c equal to or greater than 6.5% as the
      diagnostic criterion for type 2 diabetes. Inductively coupled plasma-mass
      spectrometry determined toenail magnesium. Mean toenail magnesium in participants
      with and without type 2 diabetes was 263.0 +/- 170.9 and 282.3 +/- 191.9
      micrograms per gram, respectively. The multivariable-adjusted odds ratio for type
      2 diabetes comparing the highest to the lowest quartile of toenail magnesium was
      0.72 (95% confidence interval, 0.52-0.99). We found a statistically significant
      interaction between toenail magnesium and geographic region on the prevalence of
      type 2 diabetes (p for interaction = 0.009). Our findings suggest that toenail
      magnesium is inversely associated with the prevalence of type 2 diabetes.
      Promoting the intake of magnesium-rich foods may bring considerable benefits for
      the prevention of type 2 diabetes, especially in those at high risk.

PMID- 28749416
TI  - Anti-Oxidative Stress Activity Is Essential for Amanita caesarea Mediated
      Neuroprotection on Glutamate-Induced Apoptotic HT22 Cells and an Alzheimer's
      Disease Mouse Model.
AB  - Amanita caesarea, an edible mushroom found mainly in Asia and southern Europe,
      has been reported to show good antioxidative activities. In the present study,
      the neuroprotective effects of A. caesarea aqueous extract (AC) were determined
      in an l-glutamic acid (l-Glu) induced HT22 cell apoptosis model, and in a d
      galactose (d-gal) and AlCl3-developed experimental Alzheimer's disease (AD) mouse
      model. In 25 mM of l-Glu-damaged HT22 cells, a 3-h pretreatment with AC strongly
      improved cell viability, reduced the proportion of apoptotic cells, restored
      mitochondrial function, inhibited the over-production of intracellular reactive
      oxygen species (ROS) and Ca2+, and suppressed the high expression levels of
      cleaved-caspase-3, calpain 1, apoptosis-inducing factor (AIF) and Bax. Compared
      with HT22 exposed only to l-Glu cells, AC enhanced the phosphorylation activities
      of protein kinase B (Akt) and the mammalian target of rapamycin (mTOR), and
      suppressed the phosphorylation activities of phosphatase and tensin homolog
      deleted on chromosome ten (PTEN). In the experimental AD mouse, 28-day AC
      administration at doses of 250, 500, and 1000 mg/kg/day strongly enhanced
      vertical movements and locomotor activities, increased the endurance time in the
      rotarod test, and decreased the escape latency time in the Morris water maze
      test. AC also alleviated the deposition of amyloid beta (Abeta) in the brain and
      improved the central cholinergic system function, as indicated by an increase
      acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations and a
      reduction in acetylcholine esterase (AchE) levels. Moreover, AC reduced ROS
      levels and enhanced superoxide dismutase (SOD) levels in the brain of
      experimental AD mice. Taken together, our data provide experimental evidence that
      A. caesarea may serve as potential food for treating or preventing
      neurodegenerative diseases.

PMID- 28749417
TI  - Modeling the Effect of Physical Activity on Obesity in China: Evidence from the
      Longitudinal China Health and Nutrition Study 1989-2011.
AB  - Although physical activity has been widely recognized as an important influential
      factor in determining the risk of obesity, the results in the existing literature
      empirically examining such issue are mixed. Especially for China, relevant
      studies are rarely found. One aim of this study is to test the direction of
      effects between obesity and physical activity. It uses longitudinal data to
      investigate the relationship and causality between physical activity and obesity
      for both children and adults in China. The longitudinal data and dynamic panel
      model used here can yield more solid results than the other studies employing
      cross-sectional data, particularly considering strict endogeneity and self
      selection. It is discovered that obesity does not affect children's physical
      activity but that obese children are more sedentary. For adults in China,
      physical activity can significantly reduce the weight, but not in the opposite
      direction.

PMID- 28749418
TI  - The Association between Vitamin D Insufficiency and Nonalcoholic Fatty Liver
      Disease: A Population-Based Study.
AB  - Previous studies have shown inconsistent results regarding the association
      between vitamin D insufficiency and nonalcoholic fatty liver disease (NAFLD). We
      attempted to demonstrate this relationship using population-based data. Vitamin D
      insufficiency was defined as a 25(OH)D level <=20 ng/mL. Hepatic steatosis index
      was calculated to define NAFLD. Significant fibrosis was assessed using Body mass
      index, AST/ALT Ratio, Diabetes (BARD) score. Logistic regression analyses were
      performed to determine the relationship between vitamin D insufficiency and
      NAFLD. Among 1812 participants, 409 (22.6%) had NAFLD. Patients with nonalcoholic
      fatty liver disease were more likely to be male (56.7%), had higher body mass
      index (28.1 kg/m2), and had more metabolic syndrome (57.2%). The proportion of
      vitamin D insufficiency did not differ between NAFLD and non-NAFLD (77.5% vs.
      77.4%). Logistic regression analyses showed that BMI, diabetes, and triglyceride
      level were significantly associated with NAFLD, whereas vitamin D insufficiency
      was not related. Subgroup analyses involving non-obese participants, male
      participants, and participants without metabolic syndrome showed similar results.
      The BARD score and the proportion of significant fibrosis by BARD score did not
      differ according to vitamin D status. Vitamin D insufficiency was not associated
      with the presence of NAFLD as assessed by validated noninvasive prediction
      models.

PMID- 28749419
TI  - Consuming Almonds vs. Isoenergetic Baked Food Does Not Differentially Influence
      Postprandial Appetite or Neural Reward Responses to Visual Food Stimuli.
AB  - Nuts have high energy and fat contents, but nut intake does not promote weight
      gain or obesity, which may be partially explained by their proposed high satiety
      value. The primary aim of this study was to assess the effects of consuming
      almonds versus a baked food on postprandial appetite and neural responses to
      visual food stimuli. Twenty-two adults (19 women and 3 men) with a BMI between 25
      and 40 kg/m2 completed the current study during a 12-week behavioral weight loss
      intervention. Participants consumed either 28 g of whole, lightly salted roasted
      almonds or a serving of a baked food with equivalent energy and macronutrient
      contents in random order on two testing days prior to and at the end of the
      intervention. Pre- and postprandial appetite ratings and functional magnetic
      resonance imaging scans were completed on all four testing days. Postprandial
      hunger, desire to eat, fullness, and neural responses to visual food stimuli were
      not different following consumption of almonds and the baked food, nor were they
      influenced by weight loss. These results support energy and macronutrient
      contents as principal determinants of postprandial appetite and do not support a
      unique satiety effect of almonds independent of these variables.

PMID- 28749420
TI  - Physicochemical and Sensorial Characterization of Honey Spirits.
AB  - Distilled spirits are usually made from fermented sugar-based materials, such as
      wines or fermented fruits, but other products can be used, namely berries or
      honey. In this work, an evaluation of honey spirits is done based on its
      physicochemical and sensory characteristics. Fourteen honey spirit samples of
      different brands of honey spirit were purchased at the market and from artisan
      Portuguese producers. Several analytical determinations, namely alcoholic
      strength, dry matter, density, total acidity, chromatic characteristics,
      methanol, acetaldehyde, ethyl acetate and higher alcohols were done to
      characterize all samples. The results pointed out several differences in
      physicochemical composition of samples. In general, these drinks are
      characterized by an alcohol strength between 37.4% and 53.0% and a low methanol
      content, quite null for most samples. Samples with higher ethanol content
      corresponded to the artisanal samples. Significant differences (p < 0.05) were
      also observed in the volatile composition and chromatic characteristics
      suggesting different production technologies. A first list of sensory attributes
      was obtained for this beverage. Therefore, further research must be done in order
      to characterize this spirit drink, which has gained market value.

PMID- 28749421
TI  - DSM-5 Changes in Attention Deficit Hyperactivity Disorder and Autism Spectrum
      Disorder: Implications for Comorbid Sleep Issues.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder
      (ASD) are the most common neurodevelopmental disorders. Despite significant
      comorbidity, the previous diagnostic criteria prohibited the simultaneous
      diagnosis of both disorders. Sleep problems are highly prevalent in both
      disorders; however, these have been studied independently for ADHD and ASD. In
      the context of revised criteria in the Diagnostic Statistical Manual of Mental
      Disorders 5th edition (DSM-5) that allows combined diagnosis of ADHD and ASD,
      this short review presents an overview of relationship between sleep problems,
      ADHD and ASD, as well as conceptualizing the shared pathophysiology. The
      practical considerations for clinical management of sleep problems in combination
      with ADHD and ASD are also discussed.

PMID- 28749423
TI  - Distinct Mechanisms of Biotic and Chemical Elicitors Enable Additive Elicitation
      of the Anticancer Phytoalexin Glyceollin I.
AB  - Phytoalexins are metabolites biosynthesized in plants in response to pathogen,
      environmental, and chemical stresses that often have potent bioactivities,
      rendering them promising for use as therapeutics or scaffolds for pharmaceutical
      development. Glyceollin I is an isoflavonoid phytoalexin from soybean that
      exhibits potent anticancer activities and is not economical to synthesize. Here,
      we tested a range of source tissues from soybean, in addition to chemical and
      biotic elicitors, to understand how to enhance the bioproduction of glyceollin I.
      Combining the inorganic chemical silver nitrate (AgNO3) with the wall glucan
      elicitor (WGE) from the soybean pathogen Phytophthora sojae had an additive
      effect on the elicitation of soybean seeds, resulting in a yield of up to 745.1
      ug gt-1 glyceollin I. The additive elicitation suggested that the biotic and
      chemical elicitors acted largely by separate mechanisms. WGE caused a major
      accumulation of phytoalexin gene transcripts, whereas AgNO3 inhibited and
      enhanced the degradation of glyceollin I and 6"-O-malonyldaidzin, respectively.

PMID- 28749422
TI  - Metamaterials and Metasurfaces for Sensor Applications.
AB  - Electromagnetic metamaterials (MMs) and metasurfaces (MSs) are artificial media
      and surfaces with subwavelength separations of meta-atoms designed for anomalous
      manipulations of light properties. Owing to large scattering cross-sections of
      metallic/dielectric meta-atoms, it is possible to not only localize strong
      electromagnetic fields in deep subwavelength volume but also decompose and
      analyze incident light signal with ultracompact setup using MMs and MSs. Hence,
      by probing resonant spectral responses from extremely boosted interactions
      between analyte layer and optical MMs or MSs, sensing the variation of refractive
      index has been a popular and practical application in the field of photonics.
      Moreover, decomposing and analyzing incident light signal can be easily achieved
      with anisotropic MSs, which can scatter light to different directions according
      to its polarization or wavelength. In this paper, we present recent advances and
      potential applications of optical MMs and MSs for refractive index sensing and
      sensing light properties, which can be easily integrated with various electronic
      devices. The characteristics and performances of devices are summarized and
      compared qualitatively with suggestions of design guidelines.

PMID- 28749424
TI  - Drug Discovery by Molecular Imaging and Monitoring Therapy Response in Lymphoma.
AB  - Molecular imaging allows a noninvasive assessment of biochemical and biological
      processes in living subjects. Treatment strategies for malignant lymphoma depend
      on histology and tumor stage. For the last two decades, molecular imaging has
      been the mainstay diagnostic test for the staging of malignant lymphoma and the
      assessment of response to treatment. This technology enhances our understanding
      of disease and drug activity during preclinical and clinical drug development.
      Here, we review molecular imaging applications in drug development, with an
      emphasis on oncology. Monitoring and assessing the efficacy of anti-cancer
      therapies in preclinical or clinical models are essential and the multimodal
      molecular imaging approach may represent a new stage for pharmacologic
      development in cancer. Monitoring the progress of lymphoma therapy with imaging
      modalities will help patients. Identifying and addressing key challenges is
      essential for successful integration of molecular imaging into the drug
      development process. In this review, we highlight the general usefulness of
      molecular imaging in drug development and radionuclide-based reporter genes.
      Further, we discuss the different molecular imaging modalities for lymphoma
      therapy and their preclinical and clinical applications.

PMID- 28749425
TI  - Recent Developments in the Medicinal Applications of Silver-NHC Complexes and
      Imidazolium Salts.
AB  - Because of their great structural diversity and multitude of chemical properties,
      N-heterocyclic carbenes (NHCs) have been utilized in a variety of capacities.
      Most recently, NHCs have been utilized as carrier molecules for many transition
      metals in medicinal chemistry. Specifically, Ag(I)-NHCs have been investigated as
      potent antibacterial agents and chemotherapeutics and have shown great efficacy
      in both in vitro and in vivo studies. Ag(I)-NHC compounds have been shown to be
      effective against a wide range of both Gram-positive and Gram-negative bacterial
      strains. Many compounds have also shown great efficacy as antitumor agents
      demonstrating comparable or better antitumor activity than standard
      chemotherapeutics such as cisplatin and 5-fluorouracil. While these compounds
      have shown great promise, clinical use has remained an unattained goal. Current
      research has been focused upon synthesis of novel Ag(I)-NHC compounds and further
      investigations of their antibacterial and antitumor activity. This review will
      focus on recent advances of Ag(I)-NHCs in medicinal applications.

PMID- 28749426
TI  - A Novel Perspective on the ApoM-S1P Axis, Highlighting the Metabolism of ApoM and
      Its Role in Liver Fibrosis and Neuroinflammation.
AB  - Hepatocytes, renal proximal tubule cells as well as the highly specialized
      endothelium of the blood brain barrier (BBB) express and secrete apolipoprotein M
      (apoM). ApoM is a typical lipocalin containing a hydrophobic binding pocket
      predominantly carrying Sphingosine-1-Phosphate (S1P). The small signaling
      molecule S1P is associated with several physiological as well as pathological
      pathways whereas the role of apoM is less explored. Hepatic apoM acts as a
      chaperone to transport S1P through the circulation and kidney derived apoM seems
      to play a role in S1P recovery to prevent urinal loss. Finally, polarized
      endothelial cells constituting the lining of the BBB express apoM and secrete the
      protein to the brain as well as to the blood compartment. The review will provide
      novel insights on apoM and S1P, and its role in hepatic fibrosis,
      neuroinflammation and BBB integrity.

PMID- 28749427
TI  - Advanced Growth Factor Delivery Systems in Wound Management and Skin
      Regeneration.
AB  - Growth factors are endogenous signaling molecules that regulate cellular
      responses required for wound healing processes such as migration, proliferation,
      and differentiation. However, exogenous application of growth factors has limited
      effectiveness in clinical settings due to their low in vivo stability, restricted
      absorption through skin around wound lesions, elimination by exudation prior to
      reaching the wound area, and other unwanted side effects. Sophisticated systems
      to control the spatio-temporal delivery of growth factors are required for the
      effective and safe use of growth factors as regenerative treatments in clinical
      practice, such as biomaterial-based drug delivery systems (DDSs). The current
      review describes the roles of growth factors in wound healing, their clinical
      applications for the treatment of chronic wounds, and advances in growth factor
      loaded DDSs for enhanced wound healing, focusing on micro- and nano-particulate
      systems, scaffolds, hydrogels, and other miscellaneous systems.

PMID- 28749428
TI  - Cannabinoid Receptor 1 and Fatty Acid Amide Hydrolase Contribute to Operant
      Sensation Seeking in Mice.
AB  - A large body of evidence in humans and preclinical models supports a role for the
      endocannabinoid system in the proper execution of motivated or goal-directed
      behaviors. Operant sensation seeking (OSS) is a task that uses varied sensory
      stimuli as a reinforcer to maintain operant responding in mice. The purpose of
      the studies in this report was to begin to explore the role of endocannabinoid
      signaling in OSS utilizing cannabinoid receptor 1 (CB1R) and fatty acid amide
      hydrolase (FAAH) knock out mice. Compared to wild type littermate controls, CB1R
      knock out mice exhibited significantly fewer active responses and earned
      significantly fewer reinforcers in fixed ratio and progressive ratio schedules.
      On the other hand, FAAH knock out mice exhibited increased active responses and
      earned more reinforcers than wild type littermates in fixed ratio but not
      progressive ratio schedules. These findings support the role of endocannabinoid
      signaling in motivated behaviors and also expand our understanding of the
      signaling processes involved in OSS.

PMID- 28749429
TI  - Establishment of a Site-Specific Tropospheric Model Based on Ground
      Meteorological Parameters over the China Region.
AB  - China is a country of vast territory with complicated geographical environment
      and climate conditions. With the rapid progress of the Chinese BeiDou satellite
      navigation system (BDS); more accurate tropospheric models must be applied to
      improve the accuracy of navigation and positioning. Based on the formula of the
      Saastamoinen and Callahan models; this study develops two single-site
      tropospheric models (named SAAS_S and CH_S models) for the Chinese region using
      radiosonde data from 2005 to 2012. We assess the two single-site tropospheric
      models with radiosonde data for 2013 and zenith tropospheric delay (ZTD) data
      from four International GNSS Service (IGS) stations and compare them to the
      results of the Saastamoinen and Callahan models. The experimental results show
      that: the mean accuracy of the SAAS_S model (bias: 0.19 cm; RMS: 3.19 cm) at all
      radiosonde stations is superior to those of the Saastamoinen (bias: 0.62 cm; RMS:
      3.62 cm) and CH_S (bias: -0.05 cm; RMS: 3.38 cm) models. In most Chinese regions;
      the RMS values of the SAAS_S and CH_S models are about 0.51~2.12 cm smaller than
      those of their corresponding source models. The SAAS_S model exhibits a clear
      improvement in the accuracy over the Saastamoinen model in low latitude regions.
      When the SAAS_S model is replaced by the SAAS model in the positioning of GNSS;
      the mean accuracy of vertical direction in the China region can be improved by
      1.12~1.55 cm and the accuracy of vertical direction in low latitude areas can be
      improved by 1.33~7.63 cm. The residuals of the SAAS_S model are closer to a
      normal distribution compared to those of the Saastamoinen model. Single-site
      tropospheric models based on the short period of the most recent data (for
      example 2 years) can also achieve a satisfactory accuracy. The average
      performance of the SAAS_S model (bias: 0.83 cm; RMS: 3.24 cm) at four IGS
      stations is superior to that of the Saastamoinen (bias: -0.86 cm; RMS: 3.59 cm)
      and CH_S (bias: 0.45 cm; RMS: 3.38 cm) models.

PMID- 28749430
TI  - Evaluation of the Nutritional Quality of Chinese Kale (Brassica alboglabra
      Bailey) Using UHPLC-Quadrupole-Orbitrap MS/MS-Based Metabolomics.
AB  - Chinese kale (Brassica alboglabra Bailey) is a widely consumed vegetable which is
      rich in antioxidants and anticarcinogenic compounds. Herein, we used an
      untargeted ultra-high-performance liquid chromatography (UHPLC)-Quadrupole
      Orbitrap MS/MS-based metabolomics strategy to study the nutrient profiles of
      Chinese kale. Seven Chinese kale cultivars and three different edible parts were
      evaluated, and amino acids, sugars, organic acids, glucosinolates and phenolic
      compounds were analysed simultaneously. We found that two cultivars, a purple
      stem cultivar W1 and a yellow-flower cultivar Y1, had more health-promoting
      compounds than others. The multivariate statistical analysis results showed that
      gluconapin was the most important contributor for discriminating both cultivars
      and edible parts. The purple-stem cultivar W1 had higher levels of some phenolic
      acids and flavonoids than the green stem cultivars. Compared to stems and leaves,
      the inflorescences contained more amino acids, glucosinolates and most of the
      phenolic acids. Meanwhile, the stems had the least amounts of phenolic compounds
      among the organs tested. Metabolomics is a powerful approach for the
      comprehensive understanding of vegetable nutritional quality. The results provide
      the basis for future metabolomics-guided breeding and nutritional quality
      improvement.

PMID- 28749431
TI  - IoT Service Clustering for Dynamic Service Matchmaking.
AB  - As the adoption of service-oriented paradigms in the IoT (Internet of Things)
      environment, real-world devices will open their capabilities through service
      interfaces, which enable other functional entities to interact with them. In an
      IoT application, it is indispensable to find suitable services for satisfying
      users' requirements or replacing the unavailable services. However, from the
      perspective of performance, it is inappropriate to find desired services from the
      service repository online directly. Instead, clustering services offline
      according to their similarity and matchmaking or discovering service online in
      limited clusters is necessary. This paper proposes a multidimensional model-based
      approach to measure the similarity between IoT services. Then, density-peaks
      based clustering is employed to gather similar services together according to the
      result of similarity measurement. Based on the service clustering, the algorithms
      of dynamic service matchmaking, discovery, and replacement will be performed
      efficiently. Evaluating experiments are conducted to validate the performance of
      proposed approaches, and the results are promising.

PMID- 28749432
TI  - Screening Hepatotoxic Components in Euodia rutaecarpa by UHPLC-QTOF/MS Based on
      the Spectrum-Toxicity Relationship.
AB  - Euodia rutaecarpa is a common traditional Chinese medicine (TCM) in clinical
      practice, having the ability to suppress pain and cease coughing; however, with
      the increasing reports showing that it is toxic, particularly hepatotoxic, the
      concerns raised by what cause its toxicity is growing. In the current study, an
      analysis method based on the spectrum effect has been employed to screen the
      major hepatotoxic components in Euodia rutaecarpa so that the toxic material's
      basis would be elucidated. A fingerprinting method of the Euodia rutaecarpa
      extracts (which were petroleum ether, chloroform, ethyl acetate, n-butanol, and
      water) using ultra-high-performance liquid chromatography coupled with quadrupole
      time-of-flight mass spectrometer (UHPLC-QTOF/MS) has been developed. Orthogonal
      partial least squares (OPLS) was used to establish the spectrum-toxicity
      relationship with the levels of alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) in mice serum as evaluation indices for liver injury. The
      UHPLC-MS fingerprint was established and the OPLS analytical results suggested
      that coniferin, 1-methyl-2-undecyl-4(1H)-quinolone, 1-methyl-2-[(6Z,9Z,12E)
      pentadeca triene]-4(1H)-quinolone, evocarpine, 1-methyl-2-[(Z)-7-tridecenyl]
      4(1H)-quinolone, dihydroevocarpine, and 1-methyl-2-tetradecy-4-(1H)-quinolone
      probably associated with the hepatotoxicity of Euodia rutaecarpa. This paper
      offered considerable methods and insight for the fundamental research of the
      toxic material basis of similar toxic TCMs.

PMID- 28749433
TI  - HBV Drug Resistance Substitutions Existed before the Clinical Approval of
      Nucleos(t)ide Analogues: A Bioinformatic Analysis by GenBank Data Mining.
AB  - Naturally occurring nucleos(t)ide analogue resistance (NUCr) substitution
      frequencies in the reverse transcriptase (RT) of the hepatitis B virus (HBV) were
      studied extensively after the clinical approval of nucleos(t)ide analogues (NUCs;
      year of approval 1998). We aimed to study NUCr substitutions in HBV RT sequences
      obtained before 1998 and better understand the evolution of RT sequences without
      NUC pressures. Our strategy was to retrieve HBV sequences from GenBank deposited
      before 1998. The initial search used the keywords "hepatitis B virus" or "HBV"
      and 1139 sequences were found. Data analyses included information extraction:
      sequence quality control and amino acid substitution analysis on 8 primary NUCr
      and 3 secondary substitution codons. Three hundred and ninety-four RT-containing
      sequences of 8 genotypes from 25 countries in 4 continents were selected. Twenty
      seven (6.9%) sequences were found to harbor substitutions at NUCr-related codons.
      Secondary substitutions (rtL80V and rtV173G/A/L) occurred more frequently than
      primary NUCr substitutions (rtI169L; rtA181G; T184A/S; rtS202T/R; rtM204L and
      rtM250K). Typical amino acid substitutions associated with NUCr were of rtL80V,
      rtV173L and rtT184A/S. We confirm the presence of naturally occurring typical HBV
      NUCr substitutions with very low frequencies, and secondary substitutions are
      more likely to occur than primary NUCr substitutions without the selective
      pressure of NUCs.

PMID- 28749434
TI  - Unsolved Puzzles Surrounding HCV Immunity: Heterologous Immunity Adds Another
      Dimension.
AB  - Chronic infection with hepatitis C virus (HCV) afflicts 3% of the world's
      population and can lead to serious and late-stage liver diseases. Developing a
      vaccine for HCV is challenging because the correlates of protection are uncertain
      and traditional vaccine approaches do not work. Studies of natural immunity to
      HCV in humans have resulted in many enigmas. Human beings are not immunologically
      naive because they are continually exposed to various environmental microbes and
      antigens, creating large populations of memory T cells. Heterologous immunity
      occurs when this pool of memory T cells cross-react against a new pathogen in an
      individual. Such heterologous immunity could influence the outcome when an
      individual is infected by a pathogen. We have recently made an unexpected finding
      that adenoviruses, a common environmental pathogen and an experimental vaccine
      vector, can induce robust cross-reactive immune responses against multiple
      antigens of HCV. Our unique finding of previously uncharacterized heterologous
      immunity against HCV opens new avenues to understand HCV pathogenesis and develop
      effective vaccines.

PMID- 28749435
TI  - Allelic Complexity in Long QT Syndrome: A Family-Case Study.
AB  - Congenital long QT syndrome (LQTS) is associated with high genetic and allelic
      heterogeneity. In some cases, more than one genetic variant is identified in the
      same (compound heterozygosity) or different (digenic heterozygosity) genes, and
      subjects with multiple pathogenic mutations may have a more severe disease.
      Standard-of-care clinical genetic testing for this and other arrhythmia
      susceptibility syndromes improves the identification of complex genotypes.
      Therefore, it is important to distinguish between pathogenic mutations and benign
      rare variants. We identified four genetic variants (KCNQ1-p.R583H, KCNH2-p.C108Y,
      KCNH2-p.K897T, and KCNE1-p.G38S) in an LQTS family. On the basis of in silico
      analysis, clinical data from our family, and the evidence from previous studies,
      we analyzed two mutated channels, KCNQ1-p.R583H and KCNH2-p.C108Y, using the
      whole-cell patch clamp technique. We found that KCNQ1-p.R583H was not associated
      with a severe functional impairment, whereas KCNH2-p.C108Y, a novel variant,
      encoded a non-functional channel that exerts dominant-negative effects on the
      wild-type. Notably, the common variants KCNH2-p.K897T and KCNE1-p.G38S were
      previously reported to produce more severe phenotypes when combined with disease
      causing alleles. Our results indicate that the novel KCNH2-C108Y variant can be a
      pathogenic LQTS mutation, whereas KCNQ1-p.R583H, KCNH2-p.K897T, and KCNE1-p.G38S
      could be LQTS modifiers.

PMID- 28749436
TI  - Disparities in Snacking Trends in US Adults over a 35 Year Period from 1977 to
      2012.
AB  - BACKGROUND: Previous studies have indicated that snacking is contributing to
      increased calories in the American diet, and that the contribution of snacks to
      energy intake has increased in recent decades. OBJECTIVE: The objective was to
      examine trends in the energy intake deriving from snacks and food sources of
      snacks for US adults over 35 years from 1977 to 2012, and whether these trends
      differ across sociodemographic groups. METHODS: Participants included 74,291 US
      adults aged >=19 years who participated in the 1977-1978 Nationwide Food
      Consumption Survey (NFCS); the 1989-1991 Continuing Survey of Food Intake by
      Individuals (CSFII), the 1994-1996 CSFII, the 1997-1998 CSFII, National Health
      and Nutrition Examination Survey (NHANES) 2003-2004, NHANES 2005-2006, NHANES
      2009-2010 and NHANES 2011-2012; all surveys are a stratified random sample of the
      total civilian, non-institutionalized US population. Overall patterns of
      snacking, trends in energy intake from snacking, trends in snacking food and
      beverage sources and energy intake from snacks across racial/ethnic, age,
      education and income groups were examined. RESULTS: For all US adults there was a
      significant increase in per capita energy intake from snacks from 1977 to 2012 (p
      < 0.01). Non-Hispanic blacks had the highest snacking energy intake from sugar
      sweetened beverages (SSBs) in each year (p < 0.01 for all), with a peak intake in
      2003-2006 of 76 kcal per capita per day. Intake of salty snacks increased in all
      groups between 1977 and 2012, with non-Hispanic blacks having the highest intake
      in 2009-2012 (p < 0.01). No significant differences were found between income or
      education groups. CONCLUSIONS: Results show that snacking remains a significant
      component of the US diet and the foods consumed at these snacks (SSBs, desserts
      and sweets and salty snacks) are not the types of foods recommended by the US
      dietary guidelines. Our finding that non-Hispanic blacks are consuming a higher
      proportion of SSBs and salty snacks than other groups, and showing the largest
      increase in energy intake deriving from snacks overall over the past 35 years, is
      indeed concerning.

PMID- 28749437
TI  - Curvature and Temperature Measurement Based on a Few-Mode PCF Formed M-Z-I and an
      Embedded FBG.
AB  - We have experimentally demonstrated an optical fiber Mach-Zehnder interferometer
      (MZI) structure formed by a few-mode photonic crystal fiber (PCF) for curvature
      measurement and inscribed a fiber Bragg grating (FBG) in the PCF for the purpose
      of simultaneously measuring temperature. The structure consists of a PCF
      sandwiched between two multi-mode fibers (MMFs). Bending experimental results
      show that the proposed sensor has a sensitivity of -1.03 nm/m-1 at a curvature
      range from 10 m-1 to 22.4 m-1, and the curvature sensitivity of the embedded FBG
      was -0.003 nm/m-1. Temperature response experimental results showed that the
      MZI's wavelength, lambdaa, has a sensitivity of 60.3 pm/ degrees C, and the FBG's
      Bragg wavelength, lambdab, has sensitivity of 9.2 pm/ degrees C in the
      temperature range of 8 to 100  degrees C. As such, it can be used for
      simultaneous measurement of curvature and temperature over ranges of 10 m-1 to
      22.4 m-1 and 8  degrees C to 100  degrees C, respectively. The results show that
      the embedded FBG can be a good indicator to compensate the varying ambient
      temperature during a curvature measurement.

PMID- 28749438
TI  - Synthesis and Identification of Novel Berberine Derivatives as Potent Inhibitors
      against TNF-alpha-Induced NF-kappaB Activation.
AB  - Twenty-three new berberine (BBR) analogues defined on substituents of ring D were
      synthesized and evaluated for their activity for suppression of tumor necrosis
      factor (TNF)-alpha-induced nuclear factor (NF)-kappaB activation. Structure
      activity relationship (SAR) analysis indicated that suitable tertiary/quaternary
      carbon substitutions at the 9-position or rigid fragment at position 10 might be
      beneficial for enhancing their anti-inflammatory potency. Among them, compounds
      2d, 2e, 2i and 2j exhibited satisfactory inhibitory potency against NF-kappaB
      activation, with an inhibitory rate of around 90% (5 MUM), much better than BBR.
      A preliminary mechanism study revealed that all of them could inhibit TNF-alpha
      induced NF-kappaB activation via impairing IkappaB kinase (IKK) phosphorylation
      as well as cytokines interleukin (IL)-6 and IL-8 induced by TNF-alpha. Therefore,
      the results provided powerful information on further structural modifications and
      development of BBR derivatives into a new class of anti-inflammatory candidates
      for the treatment of inflammatory diseases.

PMID- 28749439
TI  - Effects of Melatonin on Early Pregnancy in Mouse: Involving the Regulation of
      StAR, Cyp11a1, and Ihh Expression.
AB  - To test whether melatonin plays an important role in the process of early
      pregnancy, melatonin was given in drinking water to pregnant mice at different
      gestation stages. These included mice who were given melatonin 14 days prior to
      their successful mating (confirmed by vaginal plug) (Group A), after successful
      mating (Group B), and 14 days prior to and until after successful mating (Group
      C). Melatonin administration significantly enhanced serum as well as ovarian
      melatonin levels in the mice. It was observed that melatonin did not affect the
      natural estrous of mice. On day 0.5 of gestation (D0.5), melatonin not only
      elevated progesterone (P) secretion, but also upregulated expressions of StAR and
      Cyp11a1, the two marker genes of corpus luteum in ovaries (p < 0.05). Group A had
      a significantly lower estradiol (E2) secretion and a higher number of
      implantation sites as well as litter size than controls (p < 0.05) and also had
      an increased Ihh expression in endometrium of D7.5 gestation. Melatonin treatment
      after successful mating improved the progesterone (P) secretion at D7.5 of
      gestation (p < 0.05) and significantly induced leukaemia inhibitory factor (LIF)
      expression (p < 0.05). Our study indicates that melatonin treatment up-regulated
      the genes involved in pregnenolone synthesis in ovary and Ihh expression in
      uterine endometrium. The mechanisms of melatonin to improve embryo implantation
      related to their actions on promoting the development of corpus luteum before
      gestation and helping to specify uterine receptivity in early pregnant mice.

PMID- 28749440
TI  - Optimization of Detection Accuracy of Closed-Loop Optical Voltage Sensors Based
      on Pockels Effect.
AB  - The influence of optical parameters on the performance of closed-loop optical
      voltage sensors (OVSs) based on Pockels effect is analyzed and a control
      algorithm is proposed to suppress the nonlinearity caused by the unideal
      parameters of optical devices for optimizing the detection precision of OVSs.
      First, a quantified model of the feedback phase demonstrates how the optical
      parameters of optical devices (including light source, polarizer, 45 degrees 
      fusion point, Faraday rotator and half-wave plate) result in the nonlinearity of
      closed-loop OVSs. Then, the parameter indexes of different optical devices are
      put forward to instruct the manufacturing process of the optical system.
      Furthermore, a closed-loop control algorithm is investigated to improve the
      measurement accuracy of nonlinear OVSs considering the unideal parameters. The
      experiment results indicate that additional bias caused by undesirable optical
      parameters is obviously decreased so that the measurement accuracy of OVSs
      satisfies the demand of IEC60044-3 for 0.1 level measurement accuracy, which
      verifies the effectiveness and correctness of the methods for suppressing the
      impact of unideal optical parameters on OVSs.

PMID- 28749441
TI  - Stages of Behavioral Change for Reducing Sodium Intake in Korean Consumers:
      Comparison of Characteristics Based on Social Cognitive Theory.
AB  - High sodium intake increases the risk of cardiovascular disease. Given the
      importance of behavioral changes to reducing sodium intake, this study aims to
      investigate the stages of change and the differences in cognitive and behavioral
      characteristics by stage in Korean consumers. Adult participants (N = 3892)
      completed a questionnaire on the stages of behavioral change, recognition of
      social efforts, outcome expectancy, barriers to practice, nutrition knowledge and
      dietary behaviors, and self-efficiency related to reduced sodium intake. The
      numbers of participants in each stage of behavioral change for reducing sodium
      intake was 29.5% in the maintenance stage, 19.5% in the action stage, and 51.0%
      in the preaction stage that included the precontemplation, contemplation, and
      preparation stages. Multiple logistic regression showed that the factors
      differentiating the three stages were recognizing a supportive social
      environment, perceived barriers to the practice of reducing sodium intake, and
      self-efficacy to be conscious of sodium content and to request less salt when
      eating out. Purchasing experience of sodium-reduced products for salty foods,
      knowledge of the recommended intake of salt and the difference between sodium and
      salt, and improving dietary habits of eating salted fish, processed food, and
      salty snacks were factors for being in the action stage versus the preaction
      stage. These findings suggest that tailored intervention according to the
      characteristics of each stage is helpful in reducing sodium intake.

PMID- 28749442
TI  - Long-Term Effects of Pregnancy Complications on Maternal Health: A Review.
AB  - Background: Most pregnancy-related medical complications appear to resolve at
      delivery or shortly thereafter. Common examples are preterm labor, placental
      abruption, preeclampsia, and gestational diabetes. Women who developed such
      complications are known to be at increased risk of developing similar
      complications in future pregnancies. It has recently become evident that these
      women are at an increased risk of long term medical complications. Methods: A
      search through scientific publications in English regarding the association of
      obstetric complications and long-term maternal illness. Results: There is a clear
      association between various obstetric complications and long-term effects on
      maternal health. Conclusions: Women with a history of adverse pregnancy outcomes
      are at increased risk of cardiovascular and metabolic diseases later in life.
      Data increasingly links maternal vascular, metabolic, and inflammatory
      complications of pregnancy with an increased risk of vascular disease in later
      life.

PMID- 28749443
TI  - Study of the Interactions of Bovine Serum Albumin with the New Anti-Inflammatory
      Agent 4-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-N'-[(4-ethoxy
      phenyl)methylidene]benzohydrazide Using a Multi-Spectroscopic Approach and
      Molecular Docking.
AB  - The lipophilic derivative of thalidomide (4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2
      yl)-N'-[(4-ethoxyphenyl)methylidene]benzohydrazide, 6P) was synthesized to
      enhance its characteristics and efficacy. Earlier studies have proved the
      immunomodulatory and anti-inflammatory effects of 6P. In this study the
      interaction between bovine serum albumin (BSA) and 6P was studied using a multi
      spectroscopic approach which included UV spectrophotometry, spectrofluorimetry
      and three dimensional spectrofluorometric and molecular docking studies. Static
      quenching was involved in quenching the fluorescence of BSA by 6P, because a
      complex formation occurred between the 6P and BSA. The binding constant decreased
      with higher temperature and was in the range of 2.5 * 105-4.8 * 103 L mol-1
      suggesting an unstable complex at higher temperatures. A single binding site was
      observed and the the site probe experiments showed site II (sub-domain IIIA) of
      BSA as the binding site for 6P. The negative values of ?G0, ?H0 and ?S0 at
      (298/303/308 K) indicated spontaneous binding between 6P and BSA as well as the
      interaction was enthalpy driven and van der Waals forces and hydrogen bonding
      were involved in the interaction. The docking results and the results from the
      experimental studies are complimentary to each other and confirm that 6P binds at
      site II (sub-domain IIIA) of BSA.

PMID- 28749444
TI  - A Possible Percutaneous Penetration Pathway That Should Be Considered.
AB  - The intercellular lipids in the stratum corneum form structures composed of
      ordered phases with orthorhombic and hexagonal hydrocarbon-chain packing
      structures and, in addition, a structure composed of a disordered fluid phase.
      Although the fluid phase plays an important role in percutaneous penetration,
      little attention has been paid to it in the literature thus far. Recently, a
      method to estimate the proportion of the fluid phase within the lipids of the
      stratum corneum was proposed and it was shown to reach about 80%. However, since
      that study assumed uniform extraction of the intercellular lipids from the
      stratum corneum, the analysis might give rise to an overestimation of the
      proportion of the lipids in the fluid phase. We developed a way to investigate
      the proportion of the lipids in the fluid phase by treating with ethanol, into
      which the lipids in the fluid phase might be dominantly dissolved. From the
      experiment we pointed out the possibility that the proportion of the lipids in
      the fluid phase reached more than 50% of the whole intercellular lipids.
      Therefore, the fluid-phase region in the intercellular lipid matrix should be
      taken into account when considering the percutaneous penetration mechanism.

PMID- 28749445
TI  - A Metabolomics-Guided Exploration of the Phytochemical Constituents of Vernonia
      fastigiata with the Aid of Pressurized Hot Water Extraction and Liquid
      Chromatography-Mass Spectrometry.
AB  - Vernonia fastigiata is a multi-purpose nutraceutical plant with interesting
      biological properties. However, very little is known about its phytochemical
      composition and, thus the need for its phytochemical characterization. In the
      current study, an environmentally friendly method, pressurized hot water
      extraction (PHWE), was used to extract metabolites from the leaves of V.
      fastigiata at various temperatures (50  degrees C, 100  degrees C, 150  degrees C
      and 200  degrees C). Ultra-high performance liquid chromatography-quadrupole time
      of flight mass spectrometry (UHPLC-qTOF-MS) analysis in combination with
      chemometric methods, particularly principal component analysis (PCA) and
      liquid/gas chromatography mass spectrometry (XCMS) cloud plots, were used to
      descriptively visualize the data and identify significant metabolites extracted
      at various temperatures. A total of 25 different metabolites, including
      hydroxycinnamic acid derivatives, clovamide, deoxy-clovamide and flavonoids, were
      noted for the first time in this plant. Overall, an increase in extraction
      temperature resulted in an increase in metabolite extraction during PHWE. This
      study is the first scientific report on the phytochemical composition of V.
      fastigiata, providing insight into the components of the chemo-diversity of this
      important plant.

PMID- 28749446
TI  - Seamline Determination Based on PKGC Segmentation for Remote Sensing Image
      Mosaicking.
AB  - This paper presents a novel method of seamline determination for remote sensing
      image mosaicking. A two-level optimization strategy is applied to determine the
      seamline. Object-level optimization is executed firstly. Background regions (BRs)
      and obvious regions (ORs) are extracted based on the results of parametric kernel
      graph cuts (PKGC) segmentation. The global cost map which consists of color
      difference, a multi-scale morphological gradient (MSMG) constraint, and texture
      difference is weighted by BRs. Finally, the seamline is determined in the
      weighted cost from the start point to the end point. Dijkstra's shortest path
      algorithm is adopted for pixel-level optimization to determine the positions of
      seamline. Meanwhile, a new seamline optimization strategy is proposed for image
      mosaicking with multi-image overlapping regions. The experimental results show
      the better performance than the conventional method based on mean-shift
      segmentation. Seamlines based on the proposed method bypass the obvious objects
      and take less time in execution. This new method is efficient and superior for
      seamline determination in remote sensing image mosaicking.

PMID- 28749447
TI  - Enhanced Uptake of Fe3O4 Nanoparticles by Intestinal Epithelial Cells in a State
      of Inflammation.
AB  - Fe3O4 nanoparticles (Fe3O4 NPs) have been used for medical and drug applications,
      although the mechanisms of cellular uptake and transport need to be further
      evaluated under inflammatory conditions. In the present study, we investigated
      the uptake of Fe3O4 NPs (20, 50, 100, and 200 nm) by intestinal epithelial cells
      under inflammatory conditions via the light scattering of flow cytometry and
      inductively coupled plasma mass spectrometry (ICP-MS) techniques. The results of
      the correlation analysis indicated that the uptake ratios of Fe3O4 NPs by
      intestinal epithelial cells under inflammatory conditions were higher than those
      under the control conditions. The transportation ratios of NPs by inflammatory
      Caco-2 cells increased almost 0.8-1.2 fold compared to the control. The
      internalization of the Fe3O4 NPs in Caco-2 cells was mediated by clathrin-related
      routes in both the control and an interleukin-1beta (IL-1beta)-induced
      inflammatory condition. The level of mRNA of clathrin expressed in Caco-2 cells
      that were stimulated by IL-1beta was almost three times more than the control.
      Consistently with the mRNA expression, the level of protein in the clathrin was
      upregulated. Additionally, it was verified for the first time that the expression
      of clathrin was upregulated in IL-1beta-stimulated Caco-2 cells. Collectively,
      these results provided a further potential understanding about the mechanism of
      Fe3O4 NPs' uptake by intestinal epithelial cells under inflammatory conditions.

PMID- 28749448
TI  - Pharmacokinetic Study of Biotransformation Products from an Anxiolytic Fraction
      of Tilia americana.
AB  - An anxiolytic fraction of Tilia americana standardized in tiliroside, rutin,
      quercitrin, quercetin glucoside, and kaempferol was obtained. After oral
      administration of the fraction, the above-mentioned flavonoids were not detected
      in plasma over 24 h. However, meta and para hydroxyphenylacetic acid and
      dihydroxyphenylacetic acid (m-HPAA, p-HPAA and DOPAC) were monitored. These are
      the biotransformation compounds of the aglycones of kaempferol and quercetin;
      these aglycones are products of the other flavonoids present in the anxiolytic
      fraction. The analytical methods (HPLC) for flavonoids and the related compounds
      (m-HPAA, p-HPAA and DOPAC) were validated, determining the parameters of
      accuracy, precision, specificity or selectivity, limit of detection,
      quantification range, and robustness. The pharmacokinetic assay was performed
      with ICR mice strains, which were given 200 mg/kg of the standardized active
      fraction. The results of validation of the analytical methods were obtained,
      allowing it to be established in a validated way that no flavonoids present in
      the anxiolytic fraction of T. americana were detected in plasma. However,
      detection and follow up was possible for the serum levels of m-HPAA, p-HPAA, and
      DOPAC. The three compounds follow a two-compartment model with very similar
      parameters between m-HPAA and p-HPAA, some being different from the ones
      characterized in the pharmacokinetics of DOPAC.

PMID- 28749449
TI  - Food Sources of Sodium Intake in an Adult Mexican Population: A Sub-Analysis of
      the SALMEX Study.
AB  - Excessive dietary sodium intake increases blood pressure and cardiovascular risk.
      In Western diets, the majority of dietary sodium comes from packaged and prepared
      foods (~75%); however, in Mexico there is no available data on the main food
      sources of dietary sodium. The main objective of this study was to identify and
      characterize the major food sources of dietary sodium in a sample of the Mexican
      Salt and Mexico (SALMEX) cohort. Adult male and female participants of the SALMEX
      study who provided a complete and valid three-day food record during the baseline
      visit were included. Overall, 950 participants (mean age 38.6 +/- 10.7 years)
      were analyzed to determine the total sodium contributed by the main food sources
      of sodium identified. Mean daily sodium intake estimated by three-day food
      records and 24-h urinary sodium excretion was 2647.2 +/- 976.9 mg/day and 3497.2
      +/- 1393.0, in the overall population, respectively. Processed meat was the main
      contributor to daily sodium intake, representing 8% of total sodium intake per
      capita as measured by three-day food records. When savory bread (8%) and sweet
      bakery goods (8%) were considered together as bread products, these were the
      major contributor to daily sodium intake, accounting for the 16% of total sodium
      intake, followed by processed meat (8%), natural cheeses (5%), and tacos (5%).
      These results highlight the need for public health policies focused on reducing
      the sodium content of processed food in Mexico.

PMID- 28749450
TI  - Evaluation of Shifted Excitation Raman Difference Spectroscopy and Comparison to
      Computational Background Correction Methods Applied to Biochemical Raman Spectra.
AB  - Raman spectroscopy provides label-free biochemical information from tissue
      samples without complicated sample preparation. The clinical capability of Raman
      spectroscopy has been demonstrated in a wide range of in vitro and in vivo
      applications. However, a challenge for in vivo applications is the simultaneous
      excitation of auto-fluorescence in the majority of tissues of interest, such as
      liver, bladder, brain, and others. Raman bands are then superimposed on a
      fluorescence background, which can be several orders of magnitude larger than the
      Raman signal. To eliminate the disturbing fluorescence background, several
      approaches are available. Among instrumentational methods shifted excitation
      Raman difference spectroscopy (SERDS) has been widely applied and studied.
      Similarly, computational techniques, for instance extended multiplicative scatter
      correction (EMSC), have also been employed to remove undesired background
      contributions. Here, we present a theoretical and experimental evaluation and
      comparison of fluorescence background removal approaches for Raman spectra based
      on SERDS and EMSC.

PMID- 28749451
TI  - Characterization of Two Historic Smallpox Specimens from a Czech Museum.
AB  - Although smallpox has been known for centuries, the oldest available variola
      virus strains were isolated in the early 1940s. At that time, large regions of
      the world were already smallpox-free. Therefore, genetic information of these
      strains can represent only the very last fraction of a long evolutionary process.
      Based on the genomes of 48 strains, two clades are differentiated: Clade 1
      includes variants of variola major, and clade 2 includes West African and variola
      minor (Alastrim) strains. Recently, the genome of an almost 400-year-old
      Lithuanian mummy was determined, which fell basal to all currently sequenced
      strains of variola virus on phylogenetic trees. Here, we determined two complete
      variola virus genomes from human tissues kept in a museum in Prague dating back
      60 and 160 years, respectively. Moreover, mass spectrometry-based proteomic,
      chemical, and microscopic examinations were performed. The 60-year-old specimen
      was most likely an importation from India, a country with endemic smallpox at
      that time. The genome of the 160-year-old specimen is related to clade 2 West
      African and variola minor strains. This sequence likely represents a new endemic
      European variant of variola virus circulating in the midst of the 19th century in
      Europe.

PMID- 28749452
TI  - Combined Effects of High-Speed Railway Noise and Ground Vibrations on Annoyance.
AB  - The Shinkansen super-express railway system in Japan has greatly increased its
      capacity and has expanded nationwide. However, many inhabitants in areas along
      the railways have been disturbed by noise and ground vibration from the trains.
      Additionally, the Shinkansen railway emits a higher level of ground vibration
      than conventional railways at the same noise level. These findings imply that
      building vibrations affect living environments as significantly as the associated
      noise. Therefore, it is imperative to quantify the effects of noise and vibration
      exposures on each annoyance under simultaneous exposure. We performed a secondary
      analysis using individual datasets of exposure and community response associated
      with Shinkansen railway noise and vibration. The data consisted of six socio
      acoustic surveys, which were conducted separately over the last 20 years in
      Japan. Applying a logistic regression analysis to the datasets, we confirmed the
      combined effects of vibration/noise exposure on noise/vibration annoyance.
      Moreover, we proposed a representative relationship between noise and vibration
      exposures, and the prevalence of each annoyance associated with the Shinkansen
      railway.

PMID- 28749453
TI  - Mindfulness-Based Stress Reduction Therapy Improves Patient and Caregiver
      Reported Outcomes in Cirrhosis.
AB  - OBJECTIVES: Patient-reported outcomes such as health-related quality of life
      (HRQOL) are impaired in cirrhosis due to under-treated mood and sleep disorders,
      which can adversely impact their caregivers. Mindfulness-based stress reduction
      (MBSR) can improve patient-reported outcomes (PRO) in non-cirrhotic patients but
      their impact in cirrhosis is unclear. To evaluate the effect of MBSR and
      supportive group therapy on mood, sleep and HRQOL in cirrhotic patients and their
      caregivers. METHODS: Cirrhotic outpatients with mild depression (Beck Depression
      Inventory (BDI)>14) on screening with an adult caregiver were enrolled. At
      baseline, BDI, sleep (Pittsburgh sleep quality index PSQI, Epworth Sleepiness
      Scale, ESS), anxiety (Beck Anxiety inventory) and HRQOL (Sickness Impact Profile,
      SIP) for both patients/caregivers and caregiver burden (Zarit Burden Interview
      Short-form, ZBI-SF and perceived caregiver burden, PCB) and patient covert
      HE(CHE) status were measured. Patients who had BDI>14 at baseline, along with
      their caregivers then underwent a structured MBSR program with four weekly hour
      long group sessions interspersed with home practice using CDs. After the last
      group, all questionnaires were repeated. RESULTS: 20 patient/caregiver dyads were
      included. All patients were men (60+/-8 years MELD 12.9+/-5.7, 14 prior hepatic
      encephalopathy (HE)) while most caregivers (n=15) were women (55+/-12 years, 23+/
      14 years of relationship, 65% spouses). There was no change in patient BDI
      between screening and baseline (20.1+/-11.2 vs. 19.0+/-10.6, P=0.81). All dyads
      were able to complete the four MBSR+supportive group therapy sessions. There was
      a significant improvement in BDI (19.0+/-10.6 vs.15.6+/-8.2 P=0.01), PSQI (7.2+/
      3.7 vs. 5.5+/-3.7, P<0.001) and overall HRQOL (25.0+/-13.2 vs. 17.7+/
      14.0,P=0.01) but not in anxiety or CHE rates in patients. Similarly caregiver
      burden (ZBI-SF13.0+/-9.0 vs. 9.8+/-6.9,P=0.04, Perceived burden 72.1+/-29.9 vs.
      63.0+/-14.5,P=0.05) and depression reduced (BDI 9.1+/-7.8 vs. 5.9+/-6.0,P=0.03)
      while caregiver sleep quality (7.2+/-3.7 vs. 5.5+/-3.7,P<0.001) improved. Prior
      HE did not affect PRO change after MBSR+supportive groups but the ZBI-SF of
      caregivers taking care of HE patients improved to a greater extent (delta -1.1+/
      6.5 vs. 7.4+/-5.3 HE, P=0.04). CONCLUSION: A short program of mindfulness and
      supportive group therapy significantly improves PRO and caregiver burden in
      cirrhotic patients with depression. This non-pharmacological method could be a
      promising approach to alleviate psychosocial stress in patients with end-stage
      liver disease and their caregivers.

PMID- 28749454
TI  - The Association of Low-Penetrance Variants in DNA Repair Genes with Colorectal
      Cancer: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: Approximately 35% of colorectal cancer (CRC) risk is attributable to
      heritable factors known hereditary syndromes, accounting for 6%. The remainder
      may be due to lower penetrance polymorphisms particularly of DNA repair genes.
      DNA repair pathways, including base excision repair (BER), nucleotide excision
      repair (NER), mismatch repair (MMR), direct reversal repair (DRR), and double
      strand break repair are complex, evolutionarily conserved, and critical in
      carcinogenesis. Germline mutations in these genes are associated with high
      penetrance CRC syndromes such as Lynch syndrome. However, the association of low
      penetrance polymorphisms of DNA repair genes with CRC risk remains unclear.
      METHODS: A systematic literature review of PubMed, Embase, and HuGENet databases
      was conducted. Pre-specified criteria determined study inclusion/exclusion. Per
      allele, pooled odds ratios disclosed the risk attributed to each variant.
      Heterogeneity was investigated by subgroup analyses for ethnicity and tumor
      location; funnel plots and Egger's test assessed publication bias. RESULTS: Sixty
      one polymorphisms in 26 different DNA repair genes were identified. Meta-analyses
      for 22 polymorphisms in 17 genes revealed that six polymorphisms were
      significantly associated with CRC risk within BER (APE1, PARP1), NER (ERCC5,
      XPC), double-strand break (RAD18), and DRR (MGMT), but none within MMR. Subgroup
      analyses revealed significant association of OGG1 rs1052133 with rectal cancer
      risk. Egger's test revealed no publication bias. CONCLUSIONS: Low-penetrance
      polymorphisms in DNA repair genes alter susceptibility to CRC. Future studies
      should therefore analyze whole-genome polymorphisms and any synergistic effects
      on CRC risk.Translational impact:This knowledge may enhance CRC risk assessment
      and facilitate a more personalized approach to cancer prevention.

PMID- 28749456
TI  - Tumour vaccines: Personal training by vaccination.

PMID- 28749455
TI  - Primary Biliary Cholangitis Alters Functional Connections of the Brain's Deep
      Gray Matter.
AB  - OBJECTIVES: Fatigue, itch, depressed mood, and cognitive impairment significantly
      impact the quality of life of many patients with primary biliary cholangitis
      (PBC). Previous neuroimaging studies of non-hepatic diseases suggest that these
      symptoms are often associated with dysfunction of deep gray matter brain regions.
      We used resting-state functional magnetic resonance imaging (rsfMRI) to determine
      whether PBC patients exhibit altered functional connections of deep gray matter.
      METHODS: Twenty female non-cirrhotic PBC patients and 21 age/gender-matched
      controls underwent rsfMRI. Resting-state functional connectivity (rsFC) of deep
      gray matter brain structures (putamen, thalamus, amygdala, hippocampus) was
      compared between groups. Fatigue, itch, mood, cognitive performance, and clinical
      response to ursodeoxycholic acid (UDCA) were assessed, and their association with
      rsFC was determined. RESULTS: Relative to controls, PBC patients exhibited
      significantly increased rsFC between the putamen, thalamus, amygdala, and
      hippocampus, as well as with frontal and parietal regions. Reduced rsFC of the
      putamen and hippocampus with motor and sensory regions of the brain were also
      observed. Fatigue, itch, complete response to UDCA, and verbal working memory
      performance were also associated with altered rsFC of deep gray matter. These
      rsFC changes were independent of biochemical disease severity. CONCLUSIONS: PBC
      patients have objective evidence of altered rsFC of the brain's deep gray matter
      that is in part linked to fatigue severity, itch, response to UDCA therapy, and
      cognitive performance. These results may guide future approaches to define how
      PBC leads to altered brain connectivity and provide insight into novel targets
      for treating PBC-associated brain dysfunction and behavioral symptoms.

PMID- 28749457
TI  - The theory of disappearing microbiota and the epidemics of chronic diseases.
AB  - In recent decades, the incidence of many apparently unrelated chronic diseases
      has markedly increased. Here, I theorize that losses of particular bacterial
      species of our ancestral microbiota have altered the context in which
      immunological, metabolic and cognitive development occur in early life, which
      results in increased disease. This ominous trend suggests that we must refocus
      efforts to understand and reverse the underlying circumstances that are
      responsible for our disappearing microbiota.

PMID- 28749458
TI  - Microbiota: Baby bugs can't stop the thugs...

PMID- 28749459
TI  - Innate immunity: Alarmins rewire innate immunity in newborns.

PMID- 28749460
TI  - Asthma and allergy: Vitamin D primes neonatal immune system.

PMID- 28749461
TI  - DNMT1-maintained hypermethylation of Kruppel-like factor 5 involves in the
      progression of clear cell renal cell carcinoma.
AB  - Clear cell renal cell carcinoma (ccRCC) is the major subtype of renal cell
      carcinoma (RCC) that is resistant to conventional radiation and chemotherapy. It
      is a challenge to explore effective therapeutic targets and drugs for this kind
      of cancer. Transcription factor Kruppel-like factor 5 (KLF5) exerts diverse
      functions in various tumor types. By analyzing cohorts of the Cancer Genome Atlas
      (TCGA) data sets, we find that KLF5 expression is suppressed in ccRCC patients
      and higher level of KLF5 expression is associated with better prognostic outcome.
      Our further investigations demonstrate that KLF5 genomic loci are hypermethylated
      at proximal exon 4 and suppression of DNA methyltransferase 1 (DNMT1) expression
      by ShRNAs or a methylation inhibitor 5-Aza-CdR can recover KLF5 expression.
      Meanwhile, there is a negative correlation between expressions of KLF5 and DNMT1
      in ccRCC tissues. Ectopic KLF5 expression inhibits ccRCC cell proliferation and
      migration/invasion in vitro and decreases xenograft growth and metastasis in
      vivo. Moreover, 5-Aza-CdR, a chemotherapy drug as DNMTs' inhibitor that can
      induce KLF5 expression, suppresses ccRCC cell growth, while knockdown of KLF5
      abolishes 5-Aza-CdR-induced growth inhibition. Collectively, our data demonstrate
      that KLF5 inhibits ccRCC growth as a tumor suppressor and highlight the potential
      of 5-Aza-CdR to release KLF5 expression as a therapeutic modality for the
      treatment of ccRCC.

PMID- 28749462
TI  - Keratin 23 promotes telomerase reverse transcriptase expression and human
      colorectal cancer growth.
AB  - The overexpression of human telomerase reverse transcriptase (hTERT) has been
      associated with the proliferation and migration of colorectal cancer (CRC) cells.
      We investigated the roles of KRT23 and hTERT in promoting CRC cell proliferation
      and migration. We verified the relationship between KRT23 and hTERT in CRC using
      streptavidin-agarose pulldown and chromatin immunoprecipitation (ChIP) assays.
      One hundred and fifty-four human CRC specimens were analyzed using
      immunohistochemistry. The roles of KRT23 and hTERT in cell growth and migration
      were studied using siRNA and lentiviruses in vivo and in vitro. Western blot and
      wound scratch analyses were used to determine the signaling pathway for KRT23
      mediated activation of CRC growth and migration. Telomerase activity was measured
      by using the TeloTAGGG Telomerase PCR ELISA PLUS Kit. We identified KRT23 as a
      new hTERT promoter-binding protein. Patients with high KRT23 and hTERT expression
      had markedly shorter overall survival. Overexpression of KRT23 upregulated the
      expression of hTERT protein, hTERT promoter-driven luciferase and telomerase
      activity in CRC. Conversely, inhibition of KRT23 by a KRT23-specific siRNA
      repressed the endogenous hTERT protein, the expression of hTERT promoter-driven
      luciferase and telomerase activity. Overexpression of KRT23 also promoted CRC
      proliferation and migration. By contrast, KRT23 inhibition significantly
      inhibited tumor cell growth in vitro and in vivo. KRT23 promoted cancer stem cell
      properties and increased the expression of CD133 and CD44. These results
      demonstrate that KRT23 is an important cellular factor that promotes CRC growth
      by activating hTERT expression and that KRT23 is a potential novel therapeutic
      target for CRC.

PMID- 28749463
TI  - Cancer cell resistance to anoikis: MUC1 glycosylation comes to play.

PMID- 28749464
TI  - The cohesin complex prevents Myc-induced replication stress.
AB  - The cohesin complex is mutated in cancer and in a number of rare syndromes
      collectively known as Cohesinopathies. In the latter case, cohesin deficiencies
      have been linked to transcriptional alterations affecting Myc and its target
      genes. Here, we set out to understand to what extent the role of cohesins in
      controlling cell cycle is dependent on Myc expression and activity. Inactivation
      of the cohesin complex by silencing the RAD21 subunit led to cell cycle arrest
      due to both transcriptional impairment of Myc target genes and alterations of
      replication forks, which were fewer and preferentially unidirectional. Ectopic
      activation of Myc in RAD21 depleted cells rescued Myc-dependent transcription and
      promoted S-phase entry but failed to sustain S-phase progression due to a strong
      replicative stress response, which was associated to a robust DNA damage
      response, DNA damage checkpoint activation and synthetic lethality. Thus, the
      cohesin complex is dispensable for Myc-dependent transcription but essential to
      prevent Myc-induced replicative stress. This suggests the presence of a feed
      forward regulatory loop where cohesins by regulating Myc level control S-phase
      entry and prevent replicative stress.

PMID- 28749465
TI  - Acid sphingomyelinase mediates human CD4+ T-cell signaling: potential roles in T
      cell responses and diseases.
AB  - Acid sphingomyelinase (ASM) is a lipid hydrolase. By generating ceramide, ASM had
      been reported to have an important role in regulating immune cell functions
      inclusive of macrophages, NK cells, and CD8+ T cells, whereas the role of ASM
      bioactivity in regulation of human CD4+ T-cell functions remained uncertain.
      Recent studies have provided novel findings in this field. Upon stimulation of
      CD3 and/or CD28, ASM-dependent ceramide signaling mediates intracellular
      downstream signal cascades of CD3 and CD28, and regulates CD4+ T-cell activation
      and proliferation. Meanwhile, CD39 and CD161 have direct interactions with ASM,
      which mediates downstream signals inclusive of STAT3 and mTOR and thus defines
      human Th17 cells. Intriguingly, ASM mediates Th1 responses, but negatively
      regulates Treg functions. In this review, we summarized the pivotal roles of ASM
      in regulation of human CD4+ T-cell activation and responses. ASM/sphingolipid
      signaling may be a novel target for the therapy of human autoimmune diseases.

PMID- 28749466
TI  - Knockout of MARCH2 inhibits the growth of HCT116 colon cancer cells by inducing
      endoplasmic reticulum stress.
AB  - Membrane-associated RING-CH protein 2 (MARCH2), a member of the MARCH family,
      functions in vesicle trafficking and autophagy regulation. In this study, we
      established MARCH2 knockout HCT116 cell lines using CRISPR/Cas9-mediated genome
      editing to evaluate the role of MARCH2 in colon cancer in vitro and in vivo.
      Knockout of MARCH2 suppressed cell proliferation, and promoted autophagy,
      apoptosis and G2/M phase cell cycle arrest. These effects were associated with
      activation of endoplasmic reticulum (ER) stress. In addition, loss of MARCH2
      sensitized HCT116 cells to the chemotherapy drugs etoposide and cisplatin.
      Moreover, we analyzed the clinical significance of MARCH2 in human colon
      carcinoma (n=100). High MARCH2 expression was significantly associated with
      advanced clinicopathological features and poorer overall survival in colon
      carcinoma. MARCH2 expression correlated negatively with expression of the
      unfolded protein response molecule p-PERK in colon cancer. Collectively, these
      data reveal a relationship between MARCH2, ER stress and colon cancer, and
      indicates MARCH2 may have an important role in the development and progression of
      colon cancer.

PMID- 28749467
TI  - Yet another hump for CAML: support of cell survival independent of tail-anchored
      protein insertion.

PMID- 28749468
TI  - WWOX sensitises ovarian cancer cells to paclitaxel via modulation of the ER
      stress response.
AB  - There are clear gaps in our understanding of genes and pathways through which
      cancer cells facilitate survival strategies as they become chemoresistant.
      Paclitaxel is used in the treatment of many cancers, but development of drug
      resistance is common. Along with being an antimitotic agent paclitaxel also
      activates endoplasmic reticulum (ER) stress. Here, we examine the role of WWOX
      (WW domain containing oxidoreductase), a gene frequently lost in several cancers,
      in mediating paclitaxel response. We examine the ER stress-mediated apoptotic
      response to paclitaxel in WWOX-transfected epithelial ovarian cancer (EOC) cells
      and following siRNA knockdown of WWOX. We show that WWOX-induced apoptosis
      following exposure of EOC cells to paclitaxel is related to ER stress and
      independent of the antimitotic action of taxanes. The apoptotic response to ER
      stress induced by WWOX re-expression could be reversed by WWOX siRNA in EOC
      cells. We report that paclitaxel treatment activates both the IRE-1 and PERK
      kinases and that the increase in paclitaxel-mediated cell death through WWOX is
      dependent on active ER stress pathway. Log-rank analysis of overall survival (OS)
      and progression-free survival (PFS) in two prominent EOC microarray data sets
      (Tothill and The Cancer Genome Atlas), encompassing ~800 patients in total,
      confirmed clinical relevance to our findings. High WWOX mRNA expression predicted
      longer OS and PFS in patients treated with paclitaxel, but not in patients who
      were treated with only cisplatin. The association of WWOX and survival was
      dependent on the expression level of glucose-related protein 78 (GRP78), a key ER
      stress marker in paclitaxel-treated patients. We conclude that WWOX sensitises
      EOC to paclitaxel via ER stress-induced apoptosis, and predicts clinical outcome
      in patients. Thus, ER stress response mechanisms could be targeted to overcome
      chemoresistance in cancer.

PMID- 28749469
TI  - Zinc oxide nanoparticles harness autophagy to induce cell death in lung
      epithelial cells.
AB  - Although zinc oxide nanoparticles (ZnONPs) are widely used, they have raised
      concerns of toxicity in humans. Previous studies have indicated that reactive
      oxygen species (ROS) and autophagy are involved in the cytotoxicity of ZnONPs,
      but the regulatory mechanisms between autophagy and ROS remain to be elucidated.
      Herein, we comprehensively investigated the regulatory mechanism of autophagy and
      the link between autophagy and ROS in ZnONPs-treated lung epithelial cells. We
      demonstrated that ZnONPs could induce autophagy, and this process could enhance
      the dissolution of ZnONPs in lysosomes to release zinc ions. Sequentially, zinc
      ions released from ZnONPs were able to damage not only lysosomes, leading to
      impaired autophagic flux, but also mitochondria. Impaired autophagic flux
      resulted in the accumulation of damaged mitochondria, which could generate
      excessive ROS to cause cell death. We further demonstrated that the inhibition of
      autophagy by either pharmacological inhibitors or small interfering RNA (siRNA)
      mediated knockdown of Beclin-1 and AMP-activated protein kinase could ameliorate
      ZnONPs-induced cell death. Moreover, we found that lysosomal-associated membrane
      protein 1/2 (LAMP-1/2), which were the most abundant highly glycosylated protein
      in late endosomes/lysosomes, exhibited aberrant expression pattern upon treatment
      with ZnONPs. Intriguingly, LAMP-2 knockdown, but not LAMP-1 knockdown, could
      exacerbate the ROS generation and cell death induced by ZnONPs treatment.
      Meanwhile, LAMP-2 overexpression alleviated ZnONPs-induced cell death, suggesting
      that LAMP-2 was linked to this toxic phenotype induced by ZnONPs. Our results
      indicate that autophagic dysfunction could contribute to excessive ROS generation
      upon treatment with ZnONPs in lung epithelial cells, suggesting that modulating
      the autophagy process would minimize ZnONPs-associated toxicity.

PMID- 28749470
TI  - miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in
      colorectal cancer.
AB  - Colorectal cancer (CRC) is the second major cause of tumor-related deaths.
      MicroRNAs (miRNAs) have pivotal roles in CRC progression. Here, we describe the
      effect of miR-181d on CRC cell metabolism and underlying molecular mechanism. Our
      data firmly demonstrated that knockdown of miR-181d suppressed CRC cell
      proliferation, migration, and invasion by impairing glycolysis. Mechanistically,
      miR-181d stabilized c-myc through directly targeting the 3'-UTRs of CRY2 and
      FBXL3, which subsequently increased the glucose consumption and the lactate
      production. Inhibition of c-myc via siRNA or small molecular inhibitor abolished
      the oncogenic effects of miR-181d on the growth and metastasis of CRC cells.
      Furthermore, c-myc/HDAC3 transcriptional suppressor complex was found to co
      localize on the CRY2 and FBXL3 promoters, epigenetically inhibit their
      transcription, and finally induce their downregulation in CRC cells. In addition,
      miR-181d expression could be directly induced by an activation of c-myc
      signaling. Together, our data indicate an oncogenic role of miR-181d in CRC by
      promoting glycolysis, and miR-181d/CRY2/FBXL3/c-myc feedback loop might be a
      therapeutic target for patients with CRC.

PMID- 28749471
TI  - Pre-synaptic TrkB in basolateral amygdala neurons mediates BDNF signaling
      transmission in memory extinction.
AB  - Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, TrkB,
      play an essential role in memory extinction. Our previous work has shown that
      JIP3 (JNK interacted protein 3) mediates anterograde axonal transport of TrkB
      through the direct binding of its coiled-coil domain 1 (CC1) with TrkB. Here, we
      constructed a fluorescent CC1 and enhanced green fluorescent protein (EGFP) fused
      protein, CC1-EGFP, and found that CC1-EGFP could specifically interrupt TrkB
      anterograde axonal transport and its localization at the pre-synaptic site.
      Consistent with this, TrkB-mediated pre-synaptic vesicle release and retrograde
      axonal signaling transmission were disrupted by CC1-EGFP. Neuronal expression of
      CC1-EGFP in the basolateral amygdala (BLA) impaired fear memory extinction. And,
      it blocked BDNF in the BLA-induced enhancement of TrkB phosphorylation in the
      infralimbic prefrontal cortex (IL). Together, this study not only suggests that
      pre-synaptic TrkB in BLA neurons is necessary for memory extinction and
      contributes to the BDNF signaling transduction from the BLA to IL, but also
      provides CC1-EGFP as a novel tool to specifically regulate pre-synaptic TrkB
      expression in vitro and in vivo.

PMID- 28749472
TI  - Retinoic acid-induced upregulation of miR-219 promotes the differentiation of
      embryonic stem cells into neural cells.
AB  - MicroRNAs (miRNAs) regulate critical cell processes, such as apoptosis,
      proliferation, and development. However, the role of miRNAs in embryonic stem
      cell (ESC) neural differentiation induced by retinoic acid (RA) and factors that
      govern neural directional differentiation remain poorly understood. In this
      study, we demonstrated that miR-219 is sufficient in promoting mouse ESCs to
      undergo neural differentiation. We discovered that Foxj3 and Zbtb18, two target
      genes of miR-219, are not able to determine the process of RA-induced
      differentiation, however they prevent ESCs from differentiating into neural
      cells. We identified four downstream genes, namely, Olig1, Zic5, Erbb2, and
      Olig2, which are essential to the gene interaction networks for neural
      differentiation. These data explain the mechanism of RA-induced neural
      differentiation of mESCs on the basis of miRNAs and support the crucial role of
      miR-219 in neurodevelopment.

PMID- 28749473
TI  - SLC39A8 deficiency: biochemical correction and major clinical improvement by
      manganese therapy.
AB  - PurposeSLC39A8 deficiency is a severe inborn error of metabolism that is caused
      by impaired function of manganese metabolism in humans. Mutations in SLC39A8 lead
      to impaired function of the manganese transporter ZIP8 and thus manganese
      deficiency. Due to the important role of Mn2+ as a cofactor for a variety of
      enzymes, the resulting phenotype is complex and severe. The manganese-dependence
      of beta-1,4-galactosyltransferases leads to secondary hypoglycosylation, making
      SLC39A8 deficiency both a disorder of trace element metabolism and a congenital
      disorder of glycosylation. Some hypoglycosylation disorders have previously been
      treated with galactose administration. The development of an effective treatment
      of the disorder by high-dose manganese substitution aims at correcting
      biochemical, and hopefully, clinical abnormalities.MethodsTwo SCL39A8 deficient
      patients were treated with 15 and 20 mg MnSO4/kg bodyweight per day.
      Glycosylation and blood manganese were monitored closely. In addition, magnetic
      resonance imaging was performed to detect potential toxic effects of
      manganese.ResultsAll measured enzyme dysfunctions resolved completely and
      considerable clinical improvement regarding motor abilities, hearing, and other
      neurological manifestations was observed.ConclusionHigh-dose manganese
      substitution was effective in two patients with SLC39A8 deficiency. Close therapy
      monitoring by glycosylation assays and blood manganese measurements is necessary
      to prevent manganese toxicity.

PMID- 28749474
TI  - Racial/ethnic differences in multiple-gene sequencing results for hereditary
      cancer risk.
AB  - PurposeWe examined racial/ethnic differences in the usage and results of germ
      line multiple-gene sequencing (MGS) panels to evaluate hereditary cancer
      risk.MethodsWe collected genetic testing results and clinical information from
      1,483 patients who underwent MGS at Stanford University between 1 January 2013
      and 31 December 2015.ResultsAsians and Hispanics presented for MGS at younger
      ages than whites (48 and 47 vs. 55; P = 5E-16 and 5E-14). Across all panels, the
      rate of pathogenic variants (15%) did not differ significantly between racial
      groups. Rates by gene did differ: in particular, a higher percentage of whites
      than nonwhites carried pathogenic CHEK2 variants (3.8% vs. 1.0%; P = 0.002). The
      rate of a variant of uncertain significance (VUS) result was higher in nonwhites
      than whites (36% vs. 27%; P = 2E-4). The probability of a VUS increased with
      increasing number of genes tested; this effect was more pronounced for nonwhites
      than for whites (1.1% absolute difference in VUS rates testing BRCA1/2 vs. 8%
      testing 13 genes vs. 14% testing 28 genes), worsening the disparity.ConclusionIn
      this diverse cohort undergoing MGS testing, pathogenic variant rates were similar
      between racial/ethnic groups. By contrast, VUS results were more frequent among
      nonwhites, with potential significance for the impact of MGS testing by
      race/ethnicity.

PMID- 28749475
TI  - Patient care standards for primary mitochondrial disease: a consensus statement
      from the Mitochondrial Medicine Society.
AB  - The purpose of this statement is to provide consensus-based recommendations for
      optimal management and care for patients with primary mitochondrial disease. This
      statement is intended for physicians who are engaged in the diagnosis and
      management of these patients. Working group members were appointed by the
      Mitochondrial Medicine Society. The panel included members with several different
      areas of expertise. The panel members utilized surveys and the Delphi method to
      reach consensus. We anticipate that this statement will need to be updated as the
      field continues to evolve. Consensus-based recommendations are provided for the
      routine care and management of patients with primary genetic mitochondrial
      disease.

PMID- 28749476
TI  - The wide genetic landscape of clinical frontotemporal dementia: systematic
      combined sequencing of 121 consecutive subjects.
AB  - PurposeTo define the genetic spectrum and relative gene frequencies underlying
      clinical frontotemporal dementia (FTD).MethodsWe investigated the frequencies and
      mutations in neurodegenerative disease genes in 121 consecutive FTD subjects
      using an unbiased, combined sequencing approach, complemented by cerebrospinal
      fluid Abeta1-42 and serum progranulin measurements. Subjects were screened for
      C9orf72 repeat expansions, GRN and MAPT mutations, and, if negative, mutations in
      other neurodegenerative disease genes, by whole-exome sequencing (WES) (n = 108),
      including WES-based copy-number variant (CNV) analysis.ResultsPathogenic and
      likely pathogenic mutations were identified in 19% of the subjects, including
      mutations in C9orf72 (n = 8), GRN (n = 7, one 11-exon macro-deletion) and, more
      rarely, CHCHD10, TARDBP, SQSTM1 and UBQLN2 (each n = 1), but not in MAPT or TBK1.
      WES also unraveled pathogenic mutations in genes not commonly linked to FTD,
      including mutations in Alzheimer (PSEN1, PSEN2), lysosomal (CTSF, 7-exon macro
      deletion) and cholesterol homeostasis pathways (CYP27A1).ConclusionOur unbiased
      approach reveals a wide genetic spectrum underlying clinical FTD, including 11%
      of seemingly sporadic FTD. It unravels several mutations and CNVs in genes and
      pathways hitherto not linked to FTD. This suggests that clinical FTD might be the
      converging downstream result of a delicate susceptibility of frontotemporal brain
      networks to insults in various pathways.

PMID- 28749477
TI  - Mapping the genomic landscape of inherited retinal disease genes prioritizes
      genes prone to coding and noncoding copy-number variations.
AB  - PurposePart of the hidden genetic variation in heterogeneous genetic conditions
      such as inherited retinal diseases (IRDs) can be explained by copy-number
      variations (CNVs). Here, we explored the genomic landscape of IRD genes listed in
      RetNet to identify and prioritize those genes susceptible to CNV
      formation.MethodsRetNet genes underwent an assessment of genomic features and of
      CNV occurrence in the Database of Genomic Variants and literature. CNVs
      identified in an IRD cohort were characterized using targeted locus amplification
      (TLA) on extracted genomic DNA.ResultsExhaustive literature mining revealed 1,345
      reported CNVs in 81 different IRD genes. Correlation analysis between rankings of
      genomic features and CNV occurrence demonstrated the strongest correlation
      between gene size and CNV occurrence of IRD genes. Moreover, we identified and
      delineated 30 new CNVs in IRD cases, 13 of which are novel and three of which
      affect noncoding, putative cis-regulatory regions. Finally, the breakpoints of
      six complex CNVs were determined using TLA in a hypothesis-neutral
      manner.ConclusionWe propose a ranking of CNV-prone IRD genes and demonstrate the
      efficacy of TLA for the characterization of CNVs on extracted DNA. Finally, this
      IRD-oriented CNV study can serve as a paradigm for other genetically
      heterogeneous Mendelian diseases with hidden genetic variation.

PMID- 28749478
TI  - Molecular autopsy in maternal-fetal medicine.
AB  - PurposeThe application of genomic sequencing to investigate unexplained death
      during early human development, a form of lethality likely enriched for severe
      Mendelian disorders, has been limited.MethodsIn this study, we employed exome
      sequencing as a molecular autopsy tool in a cohort of 44 families with at least
      one death or lethal fetal malformation at any stage of in utero development.
      Where no DNA was available from the fetus, we performed molecular autopsy by
      proxy, i.e., through parental testing.ResultsPathogenic or likely pathogenic
      variants were identified in 22 families (50%), and variants of unknown
      significance were identified in further 15 families (34%). These variants were in
      genes known to cause embryonic or perinatal lethality (ALPL, GUSB, SLC17A5,
      MRPS16, THSD1, PIEZO1, and CTSA), genes known to cause Mendelian phenotypes that
      do not typically include embryonic lethality (INVS, FKTN, MYBPC3, COL11A2, KRIT1,
      ASCC1, NEB, LZTR1, TTC21B, AGT, KLHL41, GFPT1, and WDR81) and genes with no
      established links to human disease that we propose as novel candidates supported
      by embryonic lethality of their orthologs or other lines of evidence (MS4A7,
      SERPINA11, FCRL4, MYBPHL, PRPF19, VPS13D, KIAA1109, MOCS3, SVOPL, FEN1, HSPB11,
      KIF19, and EXOC3L2).ConclusionOur results suggest that molecular autopsy in
      pregnancy losses is a practical and high-yield alternative to traditional
      autopsy, and an opportunity for bringing precision medicine to the clinical
      practice of perinatology.

PMID- 28749479
TI  - Communicating prognosis with parents of critically ill infants: direct
      observation of clinician behaviors.
AB  - OBJECTIVE: Delivering prognostic information to families requires clinicians to
      forecast an infant's illness course and future. We lack robust empirical data
      about how prognosis is shared and how that affects clinician-family concordance
      regarding infant outcomes. STUDY DESIGN: Prospective audiorecording of neonatal
      intensive care unit family conferences, immediately followed by parent/clinician
      surveys. Existing qualitative analysis frameworks were applied. RESULTS: We
      analyzed 19 conferences. Most prognostic discussion targeted predicted infant
      functional needs, for example, medications or feeding. There was little
      discussion of how infant prognosis would affect infant/family quality of life.
      Prognostic framing was typically optimistic. Most parents left the conference
      believing their infant's prognosis to be more optimistic than did clinicians.
      CONCLUSIONS: Clinician approach to prognostic disclosure in these audiotaped
      family conferences tended to be broad and optimistic, without detail regarding
      implications of infant health for infant/family quality of life. Families and
      clinicians left these conversations with little consensus about infant prognosis.

PMID- 28749480
TI  - Caffeine decreases intermittent hypoxia in preterm infants nearing term
      equivalent age.
AB  - OBJECTIVE: To determine whether intermittent hypoxia (IH) persisting after 36
      weeks postmenstrual age (PMA) can be attenuated using caffeine doses sufficient
      to maintain caffeine concentrations >20 MUg ml-1. STUDY DESIGN: Twenty-seven
      infants born <32 weeks were started on caffeine citrate at 10 mg kg-1 day-1 when
      clinical caffeine was discontinued. At 36 weeks PMA, the dose was increased to 14
      or 20 mg kg-1 day-1 divided twice a day (BID) to compensate for progressively
      increasing caffeine metabolism. Caffeine concentrations were measured weekly. The
      extent of IH derived from continuous pulse oximetry was compared to data from 53
      control infants. RESULT: The mean (s.d.) gestational age of enrolled infants was
      27.9+/-2 weeks. Median caffeine levels were >20 MUg ml-1 on study caffeine doses.
      IH was significantly attenuated through 38 weeks PMA compared with the control
      group. CONCLUSION: Caffeine doses of 14 to 20 mg kg-1 day-1 were sufficient to
      maintain caffeine concentrations >20 MUg ml-1 and reduce IH in preterm infants at
      36 to 38 weeks PMA.

PMID- 28749481
TI  - Evaluation of critical congenital heart defects screening using pulse oximetry in
      the neonatal intensive care unit.
AB  - OBJECTIVE: To evaluate the implementation of early screening for critical
      congenital heart defects (CCHDs) in the neonatal intensive care unit (NICU) and
      potential exclusion of sub-populations from universal screening. STUDY DESIGN:
      Prospective evaluation of CCHD screening at multiple time intervals was conducted
      in 21 NICUs across five states (n=4556 infants). RESULTS: Of the 4120 infants
      with complete screens, 92% did not have prenatal CHD diagnosis or
      echocardiography before screening, 72% were not receiving oxygen at 24 to 48 h
      and 56% were born ?2500 g. Thirty-seven infants failed screening (0.9%); none
      with an unsuspected CCHD. False positive rates were low for infants not receiving
      oxygen (0.5%) and those screened after weaning (0.6%), yet higher among infants
      born at <28 weeks (3.8%). Unnecessary echocardiograms were minimal (0.2%).
      CONCLUSION: Given the majority of NICU infants were ?2500 g, not on oxygen and
      not preidentified for CCHD, systematic screening at 24 to 48 h may be of benefit
      for early detection of CCHD with minimal burden.

PMID- 28749482
TI  - 'The obesity paradox': a reconsideration of obesity and the risk of preterm
      birth.
AB  - OBJECTIVE: The association between obesity and spontaneous preterm births (sPTBs)
      has been shown to be influenced by obesity-attendant comorbidities. Our objective
      was to better understand the complex relationship of obesity and its attendant
      comorbidities with sPTBs. STUDY DESIGN: A retrospective analysis utilizing
      maternally linked hospital and birth certificate records of 2 049 196 singleton
      California deliveries from 2007 to 2011. Adjusted relative risks (aRRs) for sPTBs
      were estimated using multivariate Poisson regression modeling. RESULTS: Obese
      women had higher aRRs for sPTBs than their normal body mass index (BMI) controls.
      aRRs (95% confidence interval) increased with increasing BMI category: Obese
      I=1.10 (1.08 to 1.12); Obese II=1.15 (1.12 to 1.18); and Obese III=1.26 (1.22 to
      1.30). When comparing only obese women without comorbidities to their normal BMI
      controls, aRRs reversed, that is, obese women had lower aRRs of sPTBs: Obese
      I=0.96 (0.94 to 0.98), Obese II=0.95 (0.91 to 0.98); and Obese III=0.98 (0.94 to
      1.03). This same reversal of aRR direction was also observed among women with
      comorbidities: 0.92 (0.89 to 0.96); 0.89 (0.85 to 0.93); and 0.89 (0.85 to 0.93),
      respectively. Increasing BMI increased the aRRs for sPTBs among patients with
      gestational diabetes (P<0.05), while decreasing the risk among patients with
      chronic hypertension and pregnancy-related hypertensive disease (P<0.05).
      CONCLUSIONS: The obesity and preterm birth paradox is an example of what has been
      described as 'Simpson's Paradox'. Unmeasured confounding factors mediated by
      comorbidities may explain the observed protective effect of obesity upon
      conditioning on the presence or absence of comorbidities and thus resolve the
      paradox.

PMID- 28749483
TI  - Surgical site infections in neonates are independently associated with longer
      hospitalizations.
AB  - OBJECTIVE: There is limited data characterizing the risk and impact of surgical
      site infection (SSI) in neonates; this makes it difficult to identify factors
      that increase neonatal SSI risk and to determine how SSI affects outcomes in this
      special population. STUDY DESIGN: The American College of Surgeons National
      Surgical Improvement Program Pediatric (NSQIP-P) collected data on children
      undergoing surgery at children's hospitals from 2012 to 2014. Neonates undergoing
      general surgical procedures were characterized with regard to demographic
      characteristics and comorbidities. Perioperative variables such as wound class,
      type of surgery and length of operation were also evaluated. RESULTS: Seven
      thousand three hundred and seventy-nine neonates were identified in the NSQIP-P
      participant user file. The overall SSI rate was 2.6%. Only wound class and length
      of surgery were significantly associated with SSI. Furthermore, SSI was
      independently associated with longer length of stay, even after adjusting for
      covariates. CONCLUSIONS: This is the largest study to date analyzing SSI in
      neonates. We found that perioperative variables have a more significant impact on
      SSI than patient factors, suggesting that operation-related characteristics are
      influencing SSI. Furthermore, neonates with SSI are more likely to have prolonged
      hospitalizations even after adjusting for patient comorbidities.

PMID- 28749484
TI  - Communication-related allegations against physicians caring for premature
      infants.
AB  - OBJECTIVE: Maternal-fetal medicine physicians (MFMp) and neonatal-perinatal
      medicine physicians (NPMp) caring for premature infants and their families are
      exposed to significant risk for malpractice actions. Effective communication
      practices have been implicated to decrease litigious intentions but the extent of
      miscommunication as a cause of legal action is essentially unknown in this
      population. Analysis of communication-related allegations (CRAs) may help toward
      improving patient care and physician-patient relationships as well as decrease
      litigation risks. STUDY DESIGN: We retrospectively reviewed the Westlaw database,
      a primary online legal research resource used by United States lawyers and legal
      professionals, for malpractice cases against physicians involving premature
      infants. Inclusion criteria were: 22 to 36 weeks gestational age, cases related
      to peripartum events through infant discharge and follow-up, and legal records
      with detailed factual narratives. RESULTS: The search yielded 736 legal records,
      of which 167 met full inclusion criteria. A CRA was identified in 29% (49/167) of
      included cases. MFMp and/or NPMp were named in 104 and 54 cases, respectively.
      CRAs were identified in 26% (27/104) and 35% (19/54) of MFMp- and NPMp-named
      cases, respectively, with a majority involving physician-family for both
      specialties (81% and 74%, respectively). Physician-family CRAs for MFMp and NPMp
      most often regarded lack of informed consent (50% and 57%, respectively), lack of
      full disclosure (41% and 29%, respectively) and lack of anticipatory guidance
      (36% and 21%, respectively). CONCLUSIONS: This study of a major legal database
      identifies CRAs as significant causes of legal action against MFMp and NPMp
      involved in the care of high-risk women and infants delivered preterm. Physicians
      should be especially vigilant with obtaining genuine informed consent and
      maintaining open communication with families.

PMID- 28749485
TI  - Thoracic fluid content by electric bioimpedance correlates with respiratory
      distress in newborns.
AB  - OBJECTIVE: The objective of the study was to compare thoracic fluid content (TFC)
      between newborn infants with and without respiratory distress. We tested the
      hypothesis that TFC would be higher in infants with respiratory distress. STUDY
      DESIGN: A total of 96 newborn infants, gestational age 37.9 (2.6) weeks, were
      enrolled at birth. TFC by electrical bioimpedance was recorded within 3 h after
      birth (TFC1) and at 24 h of life (TFC2). RESULTS: TFC1 was higher in infants with
      respiratory distress at birth (76.8 (24.9) versus 61.6 (16.1) 1 KOhm-1,
      P<0.0005). The association was independent from gestational age and mode of
      delivery. TFC2 was independently associated with respiratory distress at 24 h of
      life (adjusted coefficient b=0.5 (s.d. 0.02), P=0.02). CONCLUSION: TFC by
      electric bioimpedance independently correlated with the presence of respiratory
      distress at birth and at 24 h of life in late preterm and term newborn infants.

PMID- 28749486
TI  - Milestones and controversies in maternal and child health: examining a brief
      history of micronutrient fortification in the US.
AB  - Fortification of our food and drinking supply has decreased morbidity rates
      related to micronutrient deficiencies among mothers and their children,
      particularly during the perinatal and neonatal periods of development. The
      purpose of this historical review is to examine the impact of public policy
      changes related to micronutrient fortification. We provide a historical
      investigation of achievements and controversies related to iodine, vitamin D,
      fluoride and folic acid fortifications in our food and drinking supply. We also
      discuss the current status of fortification recommendations and their
      significance to maternal and child health.

PMID- 28749487
TI  - Autoimmune conditions and comorbid depression in pregnancy: examining the risk of
      preterm birth and preeclampsia.
AB  - OBJECTIVE: The objective of this study was to determine whether prenatal
      depression interacts with autoimmune conditions to further increase the risk of
      preterm birth or preeclampsia. STUDY DESIGN: Our sample included 3034 pregnant
      women with rheumatoid arthritis (RA), Crohn's disease (CD) or psoriasis, or
      controls that were prospectively enrolled into MothertoBaby pregnancy studies. We
      estimated the independent and joint effects of the three autoimmune conditions
      and depression on the select outcomes. RESULTS: We found an increased risk of
      preterm birth among women with RA (2.10; 95% confidence interval (CI) 1.54,
      2.87), CD (1.87; 95% CI 1.25, 2.81) or psoriasis (1.88; 95% CI 1.27, 2.79)
      independent of depression status. RA was also independently associated with
      preeclampsia. Prenatal depression was not independently associated with preterm
      birth or preeclampsia, nor was there any synergism with autoimmune conditions.
      CONCLUSION: If these findings are confirmed, the absence of synergism should be
      encouraging news to the many women with select autoimmune conditions and
      depression in pregnancy.

PMID- 28749488
TI  - Trends in provider-initiated versus spontaneous preterm deliveries, 2004-2013.
AB  - OBJECTIVE: The objectives of this study were as follows: (i) to estimate the
      proportion of preterm deliveries at a tertiary perinatal center that were
      provider-initiated versus spontaneous before and after a 2009 policy to reduce
      elective early-term deliveries, and (ii)to evaluate whether shifts in type of
      preterm delivery varied by race/ethnicity. METHOD: We performed a retrospective
      cohort study of preterm deliveries over a 10-year period, 2004 to 2013, including
      detailed review of 929 of 5566 preterm deliveries, to designate each delivery as
      provider-initiated or spontaneous. We dichotomized the time period into early
      (2004 to 2009) and late (2010 to 2013). We used log-binomial regression to
      calculate adjusted risk ratios. RESULT: Of the 46 981 deliveries, 5566 (11.8%)
      were preterm, with a significant reduction in the overall incidence of preterm
      delivery from 12.3 to 11.2% (P=0.0003). Among the 929 preterm deliveries
      analyzed, there was a reduction in the proportion of provider-initiated
      deliveries from 48.3 to 41.8% that was not statistically significant. The
      proportion of provider-initiated preterm deliveries among Black, but not White,
      women declined from 50.8 to 39.7% (adjusted relative risk: 0.66; 95% confidence
      interval (CI): 0.45 to 0.97). This coincided with a larger reduction in overall
      preterm deliveries among Black women (16.2 to 12.8%) vs White women (12.3 to
      11.2%) (P interaction=0.038). By 2013, the incidence of preterm deliveries had
      decreased for both Black (12.1%) and White women (11.4%), and the difference was
      no longer statistically significant (P=0.7). CONCLUSION: We found a reduction in
      preterm deliveries after a policy targeted at reducing elective early-term
      deliveries in 2009 that coincided with reductions in the proportion of provider
      initiated preterm deliveries, especially among Black women.

PMID- 28749489
TI  - Optimization of ultra-performance liquid chromatography (UPLC) with fluorescence
      detector (FLD) method for the quantitative determination of selected
      neurotransmitters in rat brain.
AB  - BACKGROUND: Glutamate (Glu) and gamma-aminobutyric acid (GABA) are the main
      neurotransmitters in the central nervous system for excitatory and inhibitory
      processes, respectively. Monitoring these neurotransmitters is an essential tool
      in establishing pathological functions, among others in terms of occupational
      exposure to toxic substances. MATERIAL AND METHODS: We present modification of
      the HPLC (high-performance liquid chromatography) to the UPLC (ultra-performance
      liquid chromatography) method for the simultaneous determination of glutamate and
      gamma-aminobutyric acid in a single injection. The isocratic separation of these
      neurotransmitter derivatives was performed on Waters Acquity BEH (ethylene
      bridged hybrid) C18 column with particle size of 1.7 MUm at 35 degrees C using a
      mobile phase consisting of 0.1 M acetate buffer (pH 6.0) and methanol (60:40,
      v/v) at a flow rate of 0.3 ml/min. The analytes were detected with the
      fluorescence detector (FLD) using derivatization with o-phthaldialdehyde (OPA),
      resulting in excitation at 340 nm and emission at 455 nm. RESULTS: Several
      validation parameters including linearity (0.999), accuracy (101.1%), intra-day
      precision (1.52-1.84%), inter-day precision (2.47-3.12%), limit of detection (5
      30 ng/ml) and quantification (100 ng/ml) were examined. The developed method was
      also used for the determination of these neurotransmitters in homogenates of
      selected rat brain structures. CONCLUSIONS: The presented UPLC-FLD is
      characterized by shorter separation time (3.5 min), which is an adaptation of the
      similar HPLC methods and is an alternative for more expensive references
      techniques such as liquid chromatography coupled with tandem mass-spectrometry
      (LC-MS/MS) methods. Med Pr 2017;68(5):583-591.

PMID- 28749490
TI  - Evidence for cooperative Na+ and Cl- binding by strongly hydrated l-proline.
AB  - In nature the amino acid l-proline (Pro) is a ubiquitous and highly effective
      osmolyte protecting cells against osmotic stress. To understand this effect
      knowledge of the hydration of Pro and its interactions with dissolved salts is
      essential. We studied these properties by combining statistical mechanics and
      broadband dielectric spectroscopy and found that Pro remains strongly hydrated up
      to high amino-acid concentrations. This is also the case upon NaCl addition to a
      0.6 M Pro solution. Here, additionally a Pro.NaCl aggregate is formed with a
      stability constant of K degrees  ~ 0.95...1.25 M-1, where Na+ and Cl-
      cooperatively bind to adjacent carboxylate-oxygen and ammonium-hydrogen atoms,
      respectively.

PMID- 28749491
TI  - A highly active Pt-Fe/gamma-Al2O3 catalyst for preferential oxidation of CO in
      excess of H2 with a wide operation temperature window.
AB  - Highly efficient Pt-Fe/gamma-Al2O3 catalysts for preferential oxidation of CO in
      excess of H2 (CO-PROX) were prepared by utilizing single-atom Fe species as
      active sites for O2 activation, which exhibited high catalytic activity and
      selectivity from 25  degrees C to 200  degrees C, with the highest Pt specific
      rate of Pt-based catalysts for CO-PROX.

PMID- 28749492
TI  - A cobalt-nitrosyl complex with a hindered hydrotris(pyrazolyl)borate coligand:
      detailed electronic structure, and reactivity towards dioxygen.
AB  - The cobalt-nitrosyl complex [Co(NO)(L3)] is supported by a highly hindered
      tridentate nitrogen ligand, hydrotris(3-tertiary butyl-5-isopropyl-1
      pyrazolyl)borate (denoted as L3-), and shows a linear Co-N-O unit. This complex
      was prepared by the reaction of the potassium salt of L3- with the cobalt
      nitrosyl precursor [Co(NO)2(tmeda)](BPh4) (tmeda = N,N,N,'N'
      tetramethylethylenediamine). The obtained cobalt-nitrosyl complex as well as the
      corresponding products from the reaction with dioxygen, [Co(eta2-O2N)(L3)] and
      [Co(eta2-O2NO)(L3)], were characterised by X-ray crystallography and a number of
      spectroscopic methods including IR/far-IR, UV-Vis, and NMR spectroscopy. We also
      performed MCD measurements and DFT calculations to further elucidate the
      electronic structure of [Co(NO)(L3)] and the optical properties of the complex.
      The MCD spectra reveal two NO-to-Co charge-transfer transitions with strong
      excited state displacements that give rise to vibrational progressions in the MCD
      spectra, indicative of a very covalent Co-NO bond. These results provide new
      insight into the properties of the Co-NO bond and the electron distribution in
      the complex, which is best described as [CoII(NO-)(L3)].

PMID- 28749493
TI  - Sulfur-directed carbon-sulfur bond cleavage for Rh-catalyzed regioselective
      alkynylthiolation of alkynes.
AB  - Sulfur-directed sp C-S bond cleavage along with a regioselective reaction with
      alkynes proceeded to give (Z)-enyne sulfides in high to excellent yields.
      Mechanistic studies were conducted, including characterization of an
      intermediate. An intramolecular variant realized the construction of a
      dibenzodithiepin skeleton, which is a seven-membered ring with two sulfur atoms.

PMID- 28749494
TI  - Two intensified fluorescence colors' switching achieved by branched dye
      nanoaggregates.
AB  - In this study, a variety of branched target dyes containing double internal
      proton transfer segments were synthesized. For comparison, some linear analogs
      including a single internal proton transfer part were synthesized. The
      corresponding reference molecules lacking proton transfer segments were also
      prepared. The properties and aggregation modes of these dye aggregates were
      investigated on the basis of scanning electron microscopy images, transmission
      electron microscopy images, dynamic light scattering, X-ray diffraction,
      UV/visible absorption spectra and fluorescence emission spectra. The results
      showed that molecular aggregates with the morphologies of nano-scaled rounded or
      cubic particles of the target branched dyes could be yielded in mixed organic
      solvent/H2O solution. A remarkable emission enhancement and fluorescence
      switching process (from bright yellow to luminous pure blue) under 365 nm lamp
      irradiation was observed for these target branched dye nanoaggregates. However,
      no aggregates of the reference branched dyes free of hydroxyl groups were formed
      and no obvious spectral variations were found. In contrast, all the studied
      linear dyes yielded molecular nanoaggregates in mixed organic solvent/H2O
      solution, and only intensified single normal blue fluorescence emission was
      presented. This study provided real examples of some branched organic dye
      aggregates which were capable of displaying naked-eye enhanced fluorescence color
      switching under an UV lamp.

PMID- 28749495
TI  - Characterization of a highly efficient antibiotic-degrading metallo-beta
      lactamase obtained from an uncultured member of a permafrost community.
AB  - Antibiotic resistance is a major global health problem, one that threatens to
      derail the benefits garnered from arguably the greatest success of modern
      medicine, the discovery of antibiotics. Among the most potent agents contributing
      to antibiotic resistance are metallo-beta-lactamases (MBLs). The discovery of MBL
      like enzymes in microorganisms that are not in contact with the human population
      is of particular concern as these proteins already have the in-built capacity to
      inactivate antibiotics, even though they may not need MBL activity for their
      survival. Here, we demonstrate that a microbiome from a remote and frozen
      environment in Alaska harbours at least one highly efficient MBL, LRA-8. LRA-8 is
      homologous to the B3 subgroup of MBLs and has a substrate profile and catalytic
      properties similar to well-known members of this enzyme family, which are
      expressed by major human pathogens. LRA-8 is predominantly a penicillinase, but
      is also active towards carbapenems, but not cephalosporins. Spectroscopic studies
      indicate that LRA-8 has an active site structure similar to that of other MBLs
      (in particular B3 subgroup representative AIM-1), and a combination of steady
      state and pre-steady-state kinetic data demonstrate that the enzyme is likely to
      employ a metal ion-bridging hydroxide to initiate catalysis. The rate-limiting
      step is the decay of a chromophoric, tetrahedral intermediate, as is observed in
      various other MBLs. Thus, studying the properties of such "pristine" MBL-like
      proteins may provide insight into the structural plasticity of this family of
      enzymes that may facilitate functional promiscuity, while important insight into
      the evolution of MBLs may also be gained.

PMID- 28749496
TI  - Electrodeposited high strength, thermally stable spectrally selective rhenium
      nickel inverse opals.
AB  - Rhenium-Nickel (RexNi100-x) based 3D metallic inverse opals (IOs) were realized
      via colloidal crystal templated electrodeposition from an aqueous electrolyte. By
      varying the electrodeposition parameters, x could be varied from 0 to 88. Under
      reducing conditions, the rhenium-rich IOs were structurally stable to
      temperatures of at least 1000  degrees C for 5 h and for at least 12 h after
      coating with a thin layer of Al2O3. This demonstrated level of thermal stability
      is significantly improved compared to previously reported electrodeposited
      refractory inverse opals with similar characteristic dimensions. A strong
      frequency dependence in the optical reflection, which ranged from ~5% around 1.5
      MUm to ~65% around 5 MUm, is predicted by simulations and experimentally
      observed, indicating the potential of this structure as a high temperature
      spectrally selective optical absorber/emitter. The elastic modulus of the ReNi IO
      structure is ~35 GPa and the hardness is ~0.8 GPa. Both these properties are much
      higher than those of Ni inverse opals and other periodically porous materials
      with similar characteristic pore dimensions. We suggest this work provides a
      promising approach for thermally stable mesostructured materials for high
      temperature catalyst supports, refractory photonics and mechanical applications
      including high temperature filtration, and high temperature actuators.

PMID- 28749497
TI  - Laterally functionalized pillar[5]arene: a new building block for covalent self
      assembly.
AB  - Laterally functionalized pillar[5]arenes were synthesized for the first time by
      bromination at the methylene bridge of dimethoxypillar[5]arene. The synthesized
      molecule was then used as a novel building block by being covalently self
      assembled into polymer nanocapsules and 2D polymer films.

PMID- 28749498
TI  - Black TiO2 based core-shell nanocomposites as doxorubicin carriers for thermal
      imaging guided synergistic therapy of breast cancer.
AB  - TiO2 nanomaterials have been widely used for anticancer drug carriers and UV/980
      nm NIR triggered cancer synergistic platforms. However, traditional pure TiO2
      nanocarriers encounter some serious drawbacks, such as low drug loading ability,
      limited tissue penetration of UV light, and heating effect of 980 nm NIR on
      normal tissue, which obstruct their further application in cancer treatment. To
      overcome those challenges, novel mesoporous silica (mSiO2) coated black TiO2 core
      shell nanocomposites are designed and constructed as doxorubicin carriers for 808
      nm NIR triggered thermal imaging guided photothermal therapy combined
      chemotherapy of breast cancer. Properties of the nanocomposites such as micro
      morphology, size, drug loading ability and release, targeting performance, and
      therapy efficiency in vitro and in vivo were evaluated. The results indicated the
      core-shell nanocomposites with dramatically increased loading ability were pH
      responsive/NIR-accelerated doxorubicin release nanocarriers and showed
      synergistic breast cancer treatment in vitro and in vivo. This study verifies
      that the newly prepared mSiO2 coated black TiO2 core-shell nanocarriers can
      overcome the limitations of traditional TiO2 nanocarriers and thus improve and
      broaden usage of TiO2 nanoparticles in nanomedicine.

PMID- 28749499
TI  - Elucidating nuclear motions in a plant sunscreen during photoisomerization
      through solvent viscosity effects.
AB  - We explore the effects of solvent viscosity on the trans-cis photoisomerization
      of sinapoyl malate, which is utilized as a sunscreen molecule in plants. Our
      results demonstrate that viscosity has a significant effect on the timescale for
      isomerization, providing insight into the nuclear motions involved. The
      ramifications of these findings are discussed with reference to sinapoyl malate's
      in vivo photoprotection properties.

PMID- 28749501
TI  - A mild post-functionalization method for the vanadium substituted P2W15V3 Wells
      Dawson polyoxometalate based on a copper catalyzed azide-alkyne cycloaddition.
AB  - A mild post-functionalization method, based on a copper(i) catalyzed azide-alkyne
      cycloaddition, was developed for the fragile [P2W15V3]9- (PWV). PWV was
      functionalized with an azide and used as a platform to attach various alkyne
      functionalized compounds.

PMID- 28749502
TI  - Ultrafast X-ray measurements of the glass-like, high-frequency stiffness of
      aqueous solutions.
AB  - The ultrafast dynamics of the domains surrounding solutes in aqueous solution
      were measured using laser-generating GHz phonons inside of 30 mM ferrocyanide
      solutions and the resulting molecular motions of the solutes and their hydrogen
      bonded solvation shells were detected using ultrafast X-ray absorption
      spectroscopy (UXAS). The measurements of the phonon dynamics around the solutes
      showed that the domains had a glass-like stiffness on a timescale of tens of
      picoseconds.

PMID- 28749503
TI  - Crab-shell induced synthesis of ordered macroporous carbon nanofiber arrays
      coupled with MnCo2O4 nanoparticles as bifunctional oxygen catalysts for
      rechargeable Zn-air batteries.
AB  - The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are
      traditionally carried out using noble metals (such as Pt) and metal oxides (such
      as RuO2 and IrO2) as catalysts, respectively. Nevertheless, several key issues
      such as high cost, poor stability, and detrimental environmental effects limit
      the catalytic activity of these noble metal- and metal oxide-based catalysts.
      Herein, we have designed and synthesized macroporous carbon nanofiber arrays by
      using a natural crab shell template. Subsequently, spinel MnCo2O4 nanoparticles
      were embedded into the nitrogen-doped macroporous carbon nanofiber arrays
      (NMCNAs) by a hydrothermal method. Accompanied by the good conductivity, large
      surface area and doping of nitrogen, the as-prepared MnCo2O4/NMCNA exhibited
      remarkable catalytic performance and outstanding stability for both ORR and OER
      in alkaline media. The macroporous superstructures play vital role in reducing
      the ion transport resistance and facilitating the diffusion of gaseous products
      (O2). Finally, rechargeable Zn-air batteries using the MnCo2O4/NMCNA catalyst
      displayed appreciably lower overpotentials, higher power density and better
      stability than commercial Pt/C, thus raising the prospect of functional low-cost,
      non-precious-metal bifunctional catalysts in metal-air batteries.

PMID- 28749504
TI  - Insights into the limitations of solar cells sensitized with ruthenium dyes
      revealed in time-resolved spectroscopy studies.
AB  - The substitution of iodide electrolytes with cobalt ones has led to the current
      champion laboratory efficiencies for dye-sensitized solar cells (DSSCs). However,
      unlike with organic dyes, this strategy does not work with classical ruthenium
      dyes. Therefore, we compare DSSCs sensitized with a popular Ru dye (N719) using
      both types of electrolytes by exploring the electron dynamics occurring from sub
      ps to seconds. An important limitation in the photocurrent of cobalt-based cells
      is revealed to be due to electron recombination between titania and oxidized Ru
      dyes, which is much higher than that in iodide-based cells and occurs on the time
      scale of tens and hundreds of ps. Electron recombination between titania and the
      electrolyte, taking place on the millisecond time scale, is responsible for
      further lowering of the photovoltage and fill factor of cobalt-based cells.
      Ruthenium dyes also exhibit lower absorption coefficients with respect to their
      organic counterparts. For this reason, we also investigate the effect of the
      changes in the titania layer thickness, addition of scattering nanoparticles and
      modifications in the TiCl4 treatment on DSSC performance.

PMID- 28749505
TI  - The influence of surface area, porous structure, and surface state on the
      supercapacitor performance of titanium oxynitride: implications for a
      nanostructuring strategy.
AB  - A recent surge of interest in metal (oxy)nitride materials for energy storage
      devices has given rise to the rapid development of various nanostructuring
      strategies for these materials. In supercapacitor applications, early transition
      metal (oxy)nitrides have been extensively explored, among which titanium
      oxynitride stands out due to its great potential for charge storage. Despite
      recent advances in supercapacitors based on titanium oxynitride, many underlying
      factors governing their capacitive performance remain elusive. In this work,
      nanostructured titanium oxynitride is prepared by firing an organic-inorganic
      hybrid precursor under a hot ammonia atmosphere, and the influence of its
      physical characteristics on the supercapacitor performance is investigated. New
      insights into the effects of surface area, porous structure, and surface state of
      titanium oxynitride on the supercapacitor performance are revealed through which
      a comprehensive understanding about the capacitive behavior of titanium
      oxynitride is provided. In addition, the implications of these insights for a
      nanostructuring strategy striving for higher capacitance and improved stability
      are discussed.

PMID- 28749506
TI  - The origin of high electrocatalytic activity of hydrogen peroxide reduction
      reaction by a g-C3N4/HOPG sensor.
AB  - Graphitic carbon nitride (g-C3N4) was synthesized from a low-cost precursor by
      means of a thermal process. The product was characterized by several
      spectroscopic techniques and the crystallinity was analyzed by X-ray diffraction.
      In the manufacture of the sensor, g-C3N4 was chemically exfoliated and a film was
      placed on the surface of a Highly Oriented Pyrolytic Graphite (HOPG). We compared
      the electrocatalytic activities of g-C3N4/HOPG and pristine HOPG surfaces as
      sensors for H2O2 quantification in buffer solution at pH 7. The results indicate
      that the surface of g-C3N4/HOPG exhibits striking analytical stability as well as
      reproducibility, enabling a reliable and sensitive determination within the 0.12
      120 MUM interval with a detection limit of 0.12 MUM. These results suggest that
      this g-C3N4 film is a really particularly good nano-structured material to be
      applied as a biosensor. Chemical and physical factors are responsible for the
      outstanding electrocatalytic activity observed. The N in the g-C3N4 allows huge
      uptake of H2O2 through the hydrogen-bonding interaction and the change in the
      electronic structure since the HOPG/g-C3N4 heterojunction favors the charge
      transfer process through the interface.

PMID- 28749507
TI  - Interaction of FeO- with water: anion photoelectron spectroscopy and theoretical
      calculations.
AB  - The interactions of FeO- with water molecules were studied by using photoelectron
      spectroscopy and density functional theoretical calculations. It is found that a
      dihydroxyl species, Fe(OH)2-/0, can be formed when FeO-/0 interacts with the
      first water molecule. The complexes formed via the interactions between FeO-/0
      and n water molecules can be viewed as Fe(OH)2(H2O)n-1-/0, in which (n - 1)H2O
      molecules interact with a Fe(OH)2 core. For Fe(OH)2-/0 and Fe(OH)2(H2O)-, the
      Fe(OH)2 unit has two conformers with the two OH groups oriented differently. The
      vertical detachment energies (VDEs) of FeO2H2(H2O)n-1- (n = 1-4) are measured to
      be 1.25 +/- 0.04, 1.66 +/- 0.04, 2.06 +/- 0.04, and 2.37 +/- 0.04 eV,
      respectively, by experiment. It is also worth mentioning that in the FeO2H2(H2O)-
      anion the water molecule interacts with the Fe(OH)2 core by forming a hydrogen
      bond with one of the OH groups, while in neutral FeO2H2(H2O), the water molecule
      interacts with the Fe atom of the Fe(OH)2 core via its O atom.

PMID- 28749508
TI  - Linking hygroscopicity and the surface microstructure of model inorganic salts,
      simple and complex carbohydrates, and authentic sea spray aerosol particles.
AB  - Individual airborne sea spray aerosol (SSA) particles show diversity in their
      morphologies and water uptake properties that are highly dependent on the
      biological, chemical, and physical processes within the sea subsurface and the
      sea surface microlayer. In this study, hygroscopicity data for model systems of
      organic compounds of marine origin mixed with NaCl are compared to data for
      authentic SSA samples collected in an ocean-atmosphere facility providing
      insights into the SSA particle growth, phase transitions and interactions with
      water vapor in the atmosphere. In particular, we combine single particle
      morphology analyses using atomic force microscopy (AFM) with hygroscopic growth
      measurements in order to provide important insights into particle hygroscopicity
      and the surface microstructure. For model systems, a range of simple and complex
      carbohydrates were studied including glucose, maltose, sucrose, laminarin, sodium
      alginate, and lipopolysaccharides. The measured hygroscopic growth was compared
      with predictions from the Extended-Aerosol Inorganics Model (E-AIM). It is shown
      here that the E-AIM model describes well the deliquescence transition and
      hygroscopic growth at low mass ratios but not as well for high ratios, most
      likely due to a high organic volume fraction. AFM imaging reveals that the
      equilibrium morphology of these single-component organic particles is amorphous.
      When NaCl is mixed with the organics, the particles adopt a core-shell morphology
      with a cubic NaCl core and the organics forming a shell similar to what is
      observed for the authentic SSA samples. The observation of such core-shell
      morphologies is found to be highly dependent on the salt to organic ratio and
      varies depending on the nature and solubility of the organic component.
      Additionally, single particle organic volume fraction AFM analysis of NaCl :
      glucose and NaCl : laminarin mixtures shows that the ratio of salt to organics in
      solution does not correspond exactly for individual particles - showing diversity
      within the ensemble of particles produced even for a simple two component system.

PMID- 28749509
TI  - Photosensitizer localization in amphiphilic block copolymers controls
      photodynamic therapy efficacy.
AB  - Localization of the photosensitizer conjugation site in amphiphilic block
      copolymers is shown to have a great impact on photodynamic therapy efficiency. To
      this end, an asymmetric multifunctional derivative of the azadipyrromethene boron
      difluoride chelate (aza-BODIPY) was synthesized and inserted at specific
      locations in polypeptide-based rod-coil amphiphilic block copolymers. A study of
      the photophysical properties of the vesicle nanocarriers, obtained by self
      assembly of these copolymers, as well as in vitro tests on two cancer cell lines
      were performed. This study aims at providing guidelines for the optimization of
      the synthetic design of therapeutic nanomedicines with minimal amounts of
      photosensitive molecules.

PMID- 28749510
TI  - Ring strain-dictated divergent fluorinating Prins cyclization or semipinacol
      rearrangement.
AB  - We have developed ring-strain dictated divergent diastereoselective fluorinating
      Prins cyclization reactions or semipinacol rearrangement reactions to access
      tetrahydropyrans containing a fluorohydrin or a carbonyl moiety at quaternary
      carbon centers under mild conditions, respectively.

PMID- 28749512
TI  - Excited-state intermolecular proton transfer dependent on the substitution
      pattern of anthracene-diurea compounds involved in fluorescent ON1-OFF-ON2
      response by the addition of acetate ions.
AB  - We report anthracene-diurea compounds which behave as anion sensors based on the
      fluorescence emission regulated by the substitution position on the anthracene
      ring. Anthracene-diurea compounds exhibit different excited-state intermolecular
      proton transfer (ESIPT) reactions depending on the pattern of the substituents.
      Three new anthracene-diurea compounds that have two phenylurea groups substituted
      at different positions on anthracene were synthesized. These compounds formed
      complexes with acetate ions through intermolecular hydrogen bonding between N-H
      and C[double bond, length as m-dash]O moieties in the ground state. The positions
      of the substituents greatly affected the excited-state intermolecular proton
      transfer. 1,5BPUA with urea groups at the 1 and 5 positions exhibited ESIPT
      reaction, which is energetically favorable for tautomer formation, in the
      presence of TBAAc. In contrast, 2,6BPUA with urea groups at low-electron-density
      positions (2 and 6 positions) showed no ESIPT reaction due to the inversion of
      the lowest unoccupied molecular orbital (LUMO) energy levels of the normal and
      tautomer states. Detailed spectroscopic measurements showed that the LUMO energy
      level of the normal form was lowered because the urea group acted as an electron
      withdrawing group. In addition, 9,10BPUA exhibited strong electronic interactions
      between the two phenylurea moieties at the 9 and 10 positions, resulting in an
      ON1-OFF-ON2 response for acetate ions. Our findings offer guidelines for the
      molecular design of materials with anthracene moieties based on the substitution
      patterns of anthracene derivatives.

PMID- 28749514
TI  - A copper-templated, bifunctional organocatalyst: a strongly cooperative dynamic
      system for the aldol reaction.
AB  - The study of novel metal-templated dynamic organocatalytic systems has led to the
      identification of CuSO4 as the most efficient template to assemble monofunctional
      prolinamide- and thiourea-modified pyridine ligands. The structural and
      electronic requirements to assemble an efficient catalyst have been disclosed:
      both pyridine ligands must bear a 1,3-substitution pattern, and the thiourea
      ligand serves as a reducing agent to copper(i) as well. Eventually, the
      cooperative effects achieved with such a simple system deliver high reaction
      rates and stereoselectivities at room temperature in the asymmetric aldol
      reaction, requiring only 1 mol% of copper salt.

PMID- 28749516
TI  - Computational prediction of high methane storage capacity in V-MOF-74.
AB  - The methane adsorption properties in M-MOF-74 (M = Mg, Ti, V, Cr, Mn, Co, Ni, Cu,
      and Zn) were investigated for potential adsorbed natural gas (ANG) vehicle
      applications. In particular, density functional theory (DFT) simulations were
      conducted to derive the force field parameters that were used in the grand
      canonical Monte Carlo (GCMC) simulations to obtain the methane adsorption
      isotherm curves. Our results indicate that commonly used DFT exchange correlation
      functionals (e.g. vdW-DF, vdW-DF2, PBE+D2) overestimated the methane binding
      strength to the metal sites, leading to inaccurate description of the adsorption
      properties. As such, the global scaling factor within the exchange correlation
      functional, PBE+D2, was optimized to find a suitable functional that leads to
      good agreement with the available experimental methane adsorption data. From the
      newly derived force field parameters, our computational simulations predict a
      methane uptake of 279 cm3 cm-3 in V-MOF-74 at T = 298 K and P = 65 bar (condition
      relevant to ANG storage operation), which would be higher than the current record
      holder of HKUST-1 (270 cm3 cm-3). Although the methane working capacity (65-5.8
      bar uptake difference) is low due to strong binding of methane with the V-MOF-74,
      varying the process conditions (e.g. lower adsorption temperature, higher
      desorption temperature, lower desorption pressure) can lead to a significantly
      high methane working capacity, towards the goal of meeting the DOE requirements
      for ANG technology.

PMID- 28749517
TI  - Synthesis of 3-acylindoles by oxidative rearrangement of 2-aminochalcones using a
      hypervalent iodine reagent and cyclization sequence.
AB  - An efficient one-pot method was developed for the construction of 3-acylindoles
      via oxidative rearrangement of 2-aminochalcones followed by intramolecular
      cyclization. The reaction was used to convert a variety of 2-aminochalcones into
      3-acylindoles in moderate to high yields.

PMID- 28749518
TI  - The mechanism and regioselectivities of (NHC)nickel(ii)hydride-catalyzed
      cycloisomerization of dienes: a computational study.
AB  - Transition metal-catalyzed hydroalkenylation is widely applied in organic
      synthesis to construct carbon-carbon bonds and synthesize substituted alkenes. In
      this work, the mechanism and regioselectivities of [(NHC)NiH]+-catalyzed
      intramolecular cycloisomerization of dienes are studied by density functional
      theory (DFT) calculations. Through an initial hydride insertion, [(NHC)NiH]+
      reacts with the diene substrate to generate the alkyl nickel species. This alkyl
      nickel species is the resting state of the catalytic cycle, and the
      hydroalkenylation reaction involves sequential olefin insertion and beta-hydride
      transfer. The selectivity between the possible cycloisomerization products is
      determined by both the olefin insertion and beta-hydride transfer steps. The
      olefin insertion favors the exo-cyclization due to the high ring strain of the
      insertion transition states for the endo-cyclization. In the beta-hydride
      transfer step, the hydride transfers to the internal olefin position selectively
      to avoid the steric repulsions between the bulky NHC ligand and the alkyl
      substituent of the olefin substrate. This selectivity of beta-hydride transfer
      leads to the n-exo cyclization instead of the (n - 1)-exo cyclization. These
      mechanistic insights will shed light on the future development of transition
      metal-catalyzed hydroalkenylation reactions.

PMID- 28749519
TI  - Atomic-scale computational design of hydrophobic RE surface-doped Al2O3 and TiO2.
AB  - Intrinsically hydrophobic rare-earth oxides (REOs) have emerged as a robust class
      of ceramics for a variety of applications. Recently, the hydrophobicity of REOs
      has been observed experimentally and subsequently scrutinized using electronic
      structure density functional theory (DFT) calculations. In this work, we applied
      the DFT method to analyze the possibility of tuning the wettability of commonly
      used hydrophilic Al2O3 and TiO2 by surface doping with Ce. The calculations
      indicate that Ce can preferentially segregate to the surface of Al2O3 and TiO2
      and form a Ce-rich oxide layer, which is stable under a wide range of oxygen
      chemical potentials. A remarkable increase in the water contact angle is
      predicted for Ce-doped Al2O3(0001), whereas the water contact angle calculated
      for Ce-doped TiO2(110) remains unchanged, regardless of the Ce concentration. The
      wetting properties of Ce-doped Al2O3 are governed by two factors: (1) the unique
      electronic structure of the rare-earth metal promotes hydrogen bond formation
      between H2O and surface oxygen; (2) significant relaxation of the surface Ce and
      O atoms hampers direct interaction between H2O and Al cations, preventing
      dissociative water adsorption. These results provide a valuable opportunity for
      Al2O3 surface modification, in terms of achieving hydrophobicity.

PMID- 28749520
TI  - Photocurrent spectroscopy of dye-sensitized carbon nanotubes.
AB  - Monochiral (7,5) single walled carbon nanotubes (SWCNTs) are integrated into a
      field effect transistor device in which the built-in electric field at the
      nanotube/metal contact allows for exciton separation under illumination. Variable
      wavelength spectroscopy and 2D surface mapping of devices consisting of 10-20
      nanotubes are performed in the visible region and a strong correlation between
      the nanotube's second optical transition (S22) and the photocurrent is found.
      After integration, the SWCNTs are non-covalently modified with three different
      fluorescent dye molecules with off-resonant absorption maxima at 532 nm, 565 nm,
      and 610 nm. The dyes extend the absorption properties of the nanotube and
      contribute to the photocurrent. This approach holds promise for the development
      of photo-detectors and for applications in photovoltaics and biosensing.

PMID- 28749522
TI  - Palladium-catalyzed decarboxylative, decarbonylative and dehydrogenative C(sp2)-H
      acylation at room temperature.
AB  - Over the past few decades, an impressive array of C-H activation methodology has
      been developed for organic synthesis. However, due to the inherent inertness of
      the C-H bonds (e.g. ~110 kcal mol-1 for the cleavage of C(aryl)-H bonds) harsh
      reaction conditions have been realized to overcome high energetic transition
      states resulting in a limited substrate scope and functional group tolerance.
      Therefore, the development of mild C-H functionalization protocols is in high
      demand to exploit the full potential of the C-H activation strategy in the
      synthesis of a complex molecular framework. Although, electron-rich substrates
      undergo electrophilic metalation under relatively mild conditions, electron
      deficient substrates proceed through a rate-limiting C-H insertion under forcing
      conditions at high temperature. In addition, a stoichiometric amount of toxic
      silver salt is frequently used in palladium catalysis to facilitate the C-H
      activation process which is not acceptable from the environmental and industrial
      standpoint. We report herein, a Pd(ii)-catalyzed decarboxylative C-H acylation of
      2-arylpyridines with alpha-ketocarboxylic acids under mild conditions. The
      present protocol does not require stoichiometric silver(i) salts as additives and
      proceeds smoothly at ambient temperature. A novel decarbonylative C-H acylation
      reaction has also been accomplished using aryl glyoxals as acyl surrogates.
      Finally, a practical C-H acylation via a dehydrogenative pathway has been
      demonstrated using commercially available benzaldehydes and aqueous
      hydroperoxides. We also disclose that acetonitrile solvent is optimal for the
      acylation reaction at room temperature and has a prominent role in the reaction
      outcome. Control experiments suggest that the acylation reaction via
      decarboxylative, decarbonylative and dehydrogenative proceeds through a radical
      pathway. Thus we disclose a practical protocol for the sp2 C-H acylation
      reaction.

PMID- 28749523
TI  - Questionnaire of core beliefs related to drug use and craving for assessment of
      relapse risk.
AB  - This study was aimed at designing a questionnaire for the assessment of addiction
      related core beliefs and craving. The sample comprised 215 patients (85.8% males
      and 14.2% females) in treatment for dependence to alcohol (40%), cocaine (36.3%)
      and cannabis (23.7%). Descriptive statistics were used to characterize the
      sample. Variance, regression and factorial analyses were conducted to study the
      questionnaire structure and its relation with variables such as abstinence and
      craving. Items about drug-related beliefs yielded a four-factor structure: what
      patient think that they could not do without drug use, lack of withdrawal,
      conditions required to use drugs again, and use of drugs as the only way to feel
      good. Items related to craving yielded three factors: negative emotions as
      precipitants of drug use, positive emotions, and difficulties attributed to
      coping with craving. Furthermore, beliefs were more important to predict craving
      than abstinence time. The present questionnaire allows to assess a set of
      significant factors to design prevention relapse programs.

PMID- 28749524
TI  - Academic outcomes and cognitive performance in problematic Internet users.
AB  - Only few studies have examined the relationship between problematic Internet use
      (PIU) and cognitive and academic performance in adolescents. The aim of this
      study was to analyze the differences in academic and cognitive performance
      (perception, attention, memory, verbal fluency and abstract reasoning) between
      adolescents with and without PIU. A total of 575 students from different high
      schools of the region of Alicante participated. Students were divided into two
      groups: adolescents with and without PIU (PIU and NPIU, respectively). Several
      questionnaires were administered to assess problematic Internet use, as well as
      students' academic performance. Substance use (alcohol / cannabis) was also
      assessed as exclusion criteria. A battery of neuropsychological tests was used to
      assess cognitive abilities. On the one hand, PIU users group obtained poorer
      academic results than NPIU, in terms of lower marks and more failed subjects. On
      the other hand, PIU group had a better hit ratio in the perception test than NPIU
      group. However, PIU adolescents got higher error rates for the abstract reasoning
      test. This greater number of errors, plus a similar number of hits compared to
      the NPIU group, could indicated a higher response rate for the PIU group, which
      may might be associated with greater impulsivity. As occurs in other addictive
      and non-substance-related problems studies, these results could mean difficulties
      in impulse control and regulation of response inhibition circuits in PIU users
      group. Future research is needed to analyze in depth the results presented in
      this paper.

PMID- 28749525
TI  - Perceived barriers to implementing screening and brief intervention for alcohol
      consumption by adolescents in hospital emergency department in Spain.
AB  - BACKGROUND: Screening for alcohol consumption in adolescents is widely justified
      in the health care field because of the particular vulnerability of this
      population, which starts drinking alcohol at a very early age and frequently
      consumes high levels of the same. Hospital emergency departments (ED) could be a
      good venue to manage early detection and carry out brief intervention (BI)
      programmes. OBJECTIVES: The aim of this study was to identify perceived barriers
      for medical staff of three hospitals in Spain to successfully implement a
      protocol for alcohol detection and BI for minors in the ED. METHODS: Exploratory
      qualitative analysis using focus groups with semi-structured, flexible and open
      ended questions to explore beliefs, attitudes, and barriers perceived by
      professionals to screening alcohol consumption and implementing BI in adolescents
      attended at the ED. RESULTS: The main perceived barriers by health professionals
      were lack of time, work overload, mistrust, lack of validated and simple
      screening tools, lack of training/awareness and legal concerns about informed
      consent and confidentiality. CONCLUSIONS: Barriers to screening and intervention
      in ED are similar to those described previously. It is necessary to improve
      organization of time allocated for medical consultations, avoid limiting ED
      resources, motivate staff and provide appropriate training.

PMID- 28749526
TI  - Adaptation to the Spanish population of the Substance Use Risk Profile Scale
      (SURPS) and psychometric properties.
AB  - The identification of different personality risk profiles for substance misuse is
      useful in preventing substance-related problems. This study aims to test the
      psychometric properties of a new version of the Substance Use Risk Profile Scale
      (SURPS) for Spanish college students. Cross-sectional study with 455
      undergraduate students from four Spanish universities. A new version of the
      SURPS, adapted to the Spanish population, was administered with the Beck
      Hopelessness Scale, the UPPS-P Impulsive Behavior Scale, the State-Trait Anxiety
      Inventory (STAI) and the Alcohol Use Disorders Identification Test (AUDIT).
      Internal consistency reliability ranged between 0.652 and 0.806 for the four
      SURPS subscales, while reliability estimated by split-half coefficients varied
      from 0.686 to 0.829. The estimated test-retest reliability ranged between 0.733
      and 0.868. The expected four-factor structure of the original scale was
      replicated. As evidence of convergent validity, we found that the SURPS subscales
      were significantly associated with other conceptually-relevant personality scales
      and significantly associated with alcohol use measures in theoretically-expected
      ways. This SURPS version may be a useful instrument for measuring personality
      traits related to vulnerability to substance use and misuse when targeting
      personality with preventive interventions.

PMID- 28749527
TI  - Relationship between alcohol consumption, whether linked to other substance use
      or not, and antiretroviral treatment adherence in HIV+ patients.
AB  - Hazardous alcohol consumption is a common diagnosis among people living with HIV
      infection. The relationship between alcohol consumption and poor adherence to
      antiretroviral therapy has been highlighted in different studies, yet few of them
      performed a parallel analysis of other substance use. In Spain, alcohol
      consumption is frequently associated with other substance use, mainly cannabis
      and cocaine. The aim of this study is to assess the influence of hazardous
      alcohol consumption both combined with other substances (cocaine, heroin,
      methadone and/or cannabis) or alone on antiretroviral therapy adherence in our
      social environment. We performed an observational case-control study including
      119 HIV+ individuals. We recruited 40 non-adherent patients, defined by less than
      90% compliance according to hospital pharmacy refill data, and corroborated by
      the Simplified Medication Adherence Questionnaire (SMAQ) and referring
      professional's opinion. Control cases (n=79) were defined as those patients with
      similar characteristics but considered adherent according to the same parameters.
      Data collection took place between May 2013 and September 2015. Statistical
      analysis was performed using a binary logistic regression model. Our results
      indicate that alcohol consumption decreases adherence to antiretroviral therapy.
      The use of methadone represents a statistically significant increased risk of
      poor adherence. No significant differences were found between adherent and non
      adherent groups regarding cocaine, heroin or cannabis use in this study. In
      summary, the detection of substance use and especially alcohol consumption in
      HIV+ patients can improve the effectiveness of antiretroviral therapy by
      identifying and treating at-risk individuals for a poor therapeutic adherence.

PMID- 28749528
TI  - Confidence Intervals for Omega Coefficient: Proposal for Calculus.
AB  - La confiabilidad es entendida como una propiedad metrica de las puntuaciones de
      un instrumento de medida. Recientemente se viene utilizando el coeficiente omega
      (omega) para la estimacion de la confiabilidad. No obstante, la medicion nunca es
      exacta por la influencia del error aleatorio, por esa razon es necesario calcular
      y reportar el intervalo de confianza (IC) que permite encontrar en valor
      verdadero en un rango de medida. En ese contexto, el articulo plantea una forma
      de estimar el IC mediante el metodo de bootstrap para facilitar este
      procedimiento se brindan codigos de R (un software de acceso libre) para que
      puedan realizarse los calculos de una forma amigable. Se espera que el articulo
      sirva de ayuda a los investigadores de ambito de salud.

PMID- 28749529
TI  - Effect and acceptance of silver diamine fluoride treatment on dental caries in
      primary teeth.
AB  - OBJECTIVES: Silver diamine fluoride (SDF) treatment has been identified as a
      potential solution to address the dental public health issues of untreated dental
      caries and insufficient access to care. The current study assessed the
      effectiveness of 38 percent SDF in arresting active dental caries lesions and in
      reducing or preventing associated dental pain and infections in young, at-risk
      children. METHODS: We enrolled 32 children aged 2-5 years with 118 active caries
      lesions in primary teeth from a community dental clinic in Oregon. After baseline
      examinations, carious lesions were treated with 1-2 applications of 38 percent
      SDF. Children were re-evaluated at 3-week and 3-month recalls to assess color and
      consistency changes in lesions (soft/hard). Parents were interviewed regarding
      symptoms of pain or infection and were surveyed regarding subjective feelings
      about SDF. RESULTS: Of 102 lesions (16 excluded from analyses), 100 were found to
      be arrested at first recall and all at second recall. The duration of SDF
      application was not associated with arrest of decay (P = 0.68). No incidence of
      pain or infection of an SDF-treated tooth was recorded. Parental impression of
      ease of application, taste, and esthetics was favorable. CONCLUSIONS: Our results
      suggested SDF was effective in arresting active caries lesions in primary teeth
      in young children and was well accepted by parents. SDF offers an easy and highly
      efficient nonsurgical alternative treatment to traditional restorative dental
      treatment in young children, and it has great potential to aid the dental public
      health community to address dental caries in at-risk populations.

PMID- 28749530
TI  - Parents' willingness to invest in their children's oral health.
AB  - OBJECTIVES: This study aimed to evaluate parents' Willingness to Invest (WTI) in
      their children's oral health in terms of money, visits to a dental practice, and
      brushing minutes. Objectives were to assess the association between parents' WTI
      and a) children's dental caries experience, b) children's oral hygiene behavior
      (OHB), and c) maternal education level and ethnic background. METHODS: A sample
      of 630 five to six-year-old-children was recruited from pediatric dental centers
      in the Netherlands. Children's dmft scores were extracted from personal dental
      records. Parental questionnaires were used to collect data on parents' WTI,
      children's OHB, maternal education level and ethnicity. RESULTS: On average,
      parents were willing to spend a maximum of ?37 per month, 3.0 dental visits per
      year, and 4.5 brushing minutes per day to maintain good oral health for their
      child. The mean dmft was significantly higher in children whose parents were
      willing to pay more money and visit the dentist more often (P = 0.028 and P =
      0.002, respectively), while the mean dmft was significantly lower in children of
      parents who were willing to invest more brushing minutes (P < 0.001). Parental
      WTI in terms of money and brushing minutes was higher in native and higher
      educated parents, and was associated with more favorable OHB of children.
      CONCLUSIONS: Parents' WTI in their children's oral health is related to
      children's dental caries status and reported OHB. Results suggest that children
      are better off when parents are willing to invest in self-care, rather than in
      money or dental visits.

PMID- 28749531
TI  - Brachial plexus ultrasound in a patient with myelodysplastic syndrome and
      myelosarcoma.

PMID- 28749532
TI  - Contracted Schrodinger equation in quantum phase-space.
AB  - The phase space formulation of quantum mechanics is equivalent to standard
      quantum mechanics where averages are calculated by way of phase space integration
      as in the case of classical statistical mechanics. We derive the quantum
      hierarchy equations, often called the contracted Schrodinger equation, in the
      phase space representation of quantum mechanics which involves quasi
      distributions of position and momentum. We use the Wigner distribution for the
      phase space function and the Moyal phase space eigenvalue formulation to derive
      the hierarchy. We show that the hierarchy equations in the position, momentum,
      and position-momentum representations are very similar in structure. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28749533
TI  - CHARMM force field and molecular dynamics simulations of protonated
      polyethylenimine.
AB  - As a gene delivery vector, polyethylenimine (PEI) shows one of the highest
      transfection efficiencies, while effectively protecting DNA from enzyme
      degradation. The distinctive charge pattern of protonated PEI is widely
      considered responsible for fundamental process such as DNA condensation into
      PEI/DNA polyplexes (which are able to enter cells via endocytosis), proton sponge
      effect (which triggers the release of polyplexes from endosome), and release of
      DNA from polyplexes (to be further processed inside the nucleus). Our
      investigations are largely motivated by the crucial need for a realistic
      molecular mechanics force field (FF) for PEI, and, accordingly, we focus on two
      major issues: (1) development of a new atomistic (CHARMM) FF for PEI in different
      protonation states, rigorously derived from high-quality ab initio calculations
      performed on model polymers, and (2) molecular dynamics investigations of
      solvated PEI, providing a detailed picture of the dynamic structuring thereof in
      dependence on their size and protonation state. The modeled PEI chains are
      essentially described in terms of gyration radius, end-to-end distance,
      persistence length, radial distribution functions, coordination numbers, and
      diffusion coefficients. They turn out to be more rigid than in other
      computational studies and we find diffusion coefficients in fair agreement with
      experimental data. The developed atomistic FF proves adequate for the realistic
      modeling of the size and protonation behavior of linear PEI, either as individual
      chains or composing polyplexes. (c) 2017 Wiley Periodicals, Inc.

PMID- 28749534
TI  - Polo-like-kinase 1: A key cellular target for anti-HBV therapy?

PMID- 28749535
TI  - Inhibition of histone deacetylases sensitizes EGF receptor-TK inhibitor-resistant
      non-small-cell lung cancer cells to erlotinib in vitro and in vivo.
AB  - BACKGROUND AND PURPOSE: Intrinsic and/or acquired resistance of epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly occurs in
      patients with non-small-cell lung cancer (NSCLC). Here, we developed a combined
      therapy of histone deacetylase inhibition by a novel HDAC inhibitor, YF454A, with
      erlotinib to overcome EGFR-TKI resistance in NSCLC. EXPERIMENTAL APPROACH: The
      sensitization of the effects of erlotinib by YF454A was examined in a panel of
      EGFR-TKI-resistant NSCLC cell lines in vitro and two different erlotinib
      resistant NSCLC xenograft mouse models in vivo. Western blotting and Affymetrix
      GeneChip expression analysis were further performed to determine the underlying
      mechanisms for the effects of the combination of erlotinib and YF454A. KEY
      RESULTS: YF454A and erlotinib showed a strong synergy in the suppression of cell
      growth by blocking the cell cycle and triggering cell apoptosis in EGFR-TKI
      resistant NSCLC cells. The combined treatment led to a significant decrease in
      tumour growth and tumour weight compared with single agents alone.
      Mechanistically, this combination therapy dramatically down-regulated the
      expression of several crucial EGFR-TKI resistance-related receptor tyrosine
      kinases, such as Her2, c-Met, IGF1R and AXL, at both the transcriptional and
      protein levels and consequently blocked the activation of downstream molecules
      Akt and ERK. Transcriptomic profiling analysis further revealed that YF454A and
      erlotinib synergistically suppressed the cell cycle pathway and decreased the
      transcription of cell-cycle related genes, such as MSH6 and MCM7. CONCLUSION AND
      IMPLICATIONS: Our preclinical study of YF454A provides a rationale for combining
      erlotinib with a histone deacetylase inhibitor to treat NSCLC with EGFR-TKI
      resistance.

PMID- 28749536
TI  - The lack of a relationship between physician payments from drug manufacturers and
      Medicare claims for abiraterone and enzalutamide.
AB  - BACKGROUND: Interactions between industry and prescribers have raised concerns
      regarding conflicts of interest. To the best of the authors' knowledge,
      quantitative data measuring these interactions have been limited until recently.
      In the current study, the authors sought to determine whether an association
      exists between industry payments and prescriber behavior with regard to
      abiraterone and enzalutamide. METHODS: Two Centers for Medicare and Medicaid
      Services databases were combined to analyze oncologists and urologists who
      received industry payments and/or prescribed abiraterone and enzalutamide.
      Correlation analysis was constructed on prescription count and industry payments.
      Multivariable median regression examined predictors of change in prescription
      count per dollar of industry payment. Stratifying prescribers by quantile
      evaluated threshold effects on prescribers. RESULTS: The number of prescriptions
      was similar between prescribers who did and those who did not receive industry
      payment for both drugs. The median industry payment amount to prescribers
      differed between prescribers and nonprescribers for abiraterone ($72 vs $56) and
      enzalutamide ($59 vs $31). Although no statistical association was found to exist
      between industry payment amount and prescription count for abiraterone
      prescribers, an association was found to exist for enzalutamide prescribers (rho
      = 0.31). A small change was found with regard to prescription count per dollar of
      industry payment for abiraterone (0.0007 prescriptions) and enzalutamide (0.0006
      prescriptions). The amount of industry payment needed to predict one additional
      prescription was found to be lower in the fourth and fifth quantiles compared
      with the first through third quantiles. CONCLUSIONS: No difference in
      prescription count was found to exist between prescribers who received industry
      payments and those who did not. A positive correlation was noted between industry
      payments and prescription count for enzalutamide. Ease of adoption may affect
      differences between the 2 drugs. Cancer 2017;123:4356-62. (c) 2017 American
      Cancer Society.

PMID- 28749538
TI  - Fast further purification of diastereomeric salts of a nonracemic acid by gas
      antisolvent fractionation.
AB  - A novel, green possibility of the further purification of the diastereomeric salt
      of 4-chloromandelic acid and 1-phenylethane-1-amine was developed. Gas
      antisolvent method using supercritical carbon dioxide was applied for the first
      time to precipitate the diastereomeric salts with increased purity followed by
      the supercritical fluid extraction of the dissolved diastereomers. The RR-salt
      can be purified to >99%, while fractionation-based purification of the SR-salt is
      limited to ~80%. The limiting initial diastereomeric excess correlates strongly
      with the atmospheric melting eutectic composition of the same salts, which
      suggests that despite the fast precipitation, the diastereomeric excess of the
      solid product is not kinetically determined. The efficiency of the diastereomeric
      enrichment is in the same range as that of the atmospheric reference experiments;
      however, technological advantages provided by the antisolvent precipitation
      method such as fast processing and dry product obtained suggest that this novel
      procedure is a promising alternative to the atmospheric methods.

PMID- 28749539
TI  - Indigenous health program evaluation design and methods in Australia: a
      systematic review of the evidence.
AB  - OBJECTIVE: Indigenous Australians experience a disproportionately higher burden
      of disease compared to non-Indigenous Australians. High-quality evaluation of
      Indigenous health programs is required to inform health and health services
      improvement. We aimed to quantify methodological and other characteristics of
      Australian Indigenous health program evaluations published in the peer-reviewed
      literature. METHODS: Systematic review of peer-reviewed literature (November 2009
      2014) on Indigenous health program evaluation. RESULTS: We identified 118 papers
      describing evaluations of 109 interventions; 72.0% were university/research
      institution-led. 82.2% of evaluations included a quantitative component; 49.2%
      utilised quantitative data only and 33.1% used both quantitative and qualitative
      data. The most common design was a before/after comparison (30.5%, n=36/118).
      7.6% of studies (n=9/118) used an experimental design: six individual-level and
      three cluster-randomised controlled trials. 56.8% (67/118) reported on service
      delivery/process outcomes (versus health or health risk factor outcomes) only.
      CONCLUSIONS: Given the number of Indigenous health programs that are implemented,
      few evaluations overall are published in the peer-reviewed literature and, of
      these, few use optimal methodologies such as mixed methods and experimental
      design. Implications for public health: Multiple strategies are required to
      increase high-quality, accessible evaluation in Indigenous health, including
      supporting stronger research-policy-practice partnerships and capacity building
      for evaluation by health services and government.

PMID- 28749537
TI  - Sodium channels and pain: from toxins to therapies.
AB  - : Voltage-gated sodium channels (NaV channels) are essential for the initiation
      and propagation of action potentials that critically influence our ability to
      respond to a diverse range of stimuli. Physiological and pharmacological studies
      have linked abnormal function of NaV channels to many human disorders, including
      chronic neuropathic pain. These findings, along with the description of the
      functional properties and expression pattern of NaV channel subtypes, are helping
      to uncover subtype specific roles in acute and chronic pain and revealing
      potential opportunities to target these with selective inhibitors. High
      throughput screens and automated electrophysiology platforms have identified
      natural toxins as a promising group of molecules for the development of target
      specific analgesics. In this review, the role of toxins in defining the
      contribution of NaV channels in acute and chronic pain states and their potential
      to be used as analgesic therapies are discussed. LINKED ARTICLES: This article is
      part of a themed section on Recent Advances in Targeting Ion Channels to Treat
      Chronic Pain. To view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.

PMID- 28749540
TI  - Declining prevalence of undiagnosed HIV in Melbourne: results from community
      based bio-behavioural studies of gay and bisexual men.
AB  - OBJECTIVE: To measure changes in undiagnosed HIV among gay and bisexual men (GBM)
      in Melbourne. METHODS: Undiagnosed HIV was compared between GBM recruited
      anonymously in 2008 in gay venues only and GBM anonymously or confidentially
      (results delivery) recruited in 2014 at gay venues and a community festival.
      Surveys were completed and oral fluid specimens collected for HIV testing;
      positive tests among GBM reporting being HIV-negative or unknown/untested were
      classified as undiagnosed. Tests of proportions compared serological prevalence,
      undiagnosed prevalence and participant characteristics. RESULTS: HIV prevalence
      was 9.5% and 7.1% among 639 and 993 GBM recruited in 2008 and 2014, respectively;
      undiagnosed prevalence declined significantly from 31.1% to 7.1% (p<0.001).
      Sexual risk and undiagnosed HIV was highest among venue-recruited participants in
      2014 (17.6%). Fewer diagnosed GBM participated confidentially in 2014, but this
      did not meaningfully influence comparative undiagnosed HIV prevalence.
      CONCLUSION: We provide the first estimates of changes in undiagnosed HIV in
      Australia, demonstrating a marked decline in undiagnosed HIV among GBM.
      Implications for public health: Our findings are consistent with reports of
      increases in HIV testing among GBM. Given sustained high HIV diagnosis rates, new
      testing models that encourage high frequency testing are needed to control the
      local HIV epidemic.

PMID- 28749541
TI  - Dynamic covalent bond from first principles: Diarylbibenzofuranone structural,
      electronic, and oxidation studies.
AB  - A structure that can self-heal under standard conditions is a challenge faced
      nowadays and is one of the most promising areas in smart materials science. This
      can be achieved by dynamic bonds, of which diarylbibenzofuranone (DABBF) dynamic
      covalent bond is an appealing solution. In this report, we studied the DABBF bond
      formation against arylbenzofuranone (ABF) and O2 reaction (autoxidation). Our
      results show that the barrierless DABBF bond formation is preferred over
      autoxidation due to the charge transfer process that results in the weakly bonded
      superoxide. We calculated the electronic and structural properties using total
      energy density functional theory. (c) 2017 Wiley Periodicals, Inc.

PMID- 28749542
TI  - Wi-Fi radiation exposures to children in kindergartens and schools - results
      should lessen parental concerns.

PMID- 28749543
TI  - New Multiresponsive Chromic Soft Materials: Dynamic Interconversion of Short 2,7
      Dicyanomethylenecarbazole-Based Biradicaloid and the Corresponding Cyclophane
      Tetramer.
AB  - This work reports on a quinodimethane-type molecule, 2,7-dicyanomethylene-9-(2
      ethylhexyl)carbazole (1), one of the shortest pi-conjugated biradicaloids
      reported to be stable in solution under ambient conditions. This carbazole-based
      quinoidal precursor is able to form a macrocyclic sigma-bonded tetramer (2). The
      resolved single-crystal X-ray structure of tetramer 2 shows that four molecules
      of 1 are linked together through four long (CN)2 C-C(CN)2 bonds (1.631 A)
      resulting from coupling of the unpaired electrons in biradicaloid 1. Dynamic
      interconversion between monomer 1 and cyclophane tetramer 2 is achieved by
      reversible cleavage and recovery of the four (CN)2 C-C(CN)2 bonds upon soft
      external stimuli (light absorption, temperature and pressure), which is
      accompanied by significant color changes. These novel photo-, thermo-, and
      mechanochromic properties expand the versatility of pi-conjugated biradicaloid
      compounds as novel functional materials that, in combination with spin chemistry
      and dynamic covalent chemistry, can be relevant in molecular machines, sensors,
      and switches.

PMID- 28749544
TI  - Combined electroencephalography-functional magnetic resonance imaging and
      electrical source imaging improves localization of pediatric focal epilepsy.
AB  - OBJECTIVE: Surgical treatment in epilepsy is effective if the epileptogenic zone
      (EZ) can be correctly localized and characterized. Here we use simultaneous
      electroencephalography-functional magnetic resonance imaging (EEG-fMRI) data to
      derive EEG-fMRI and electrical source imaging (ESI) maps. Their yield and their
      individual and combined ability to (1) localize the EZ and (2) predict seizure
      outcome were then evaluated. METHODS: Fifty-three children with drug-resistant
      epilepsy underwent EEG-fMRI. Interictal discharges were mapped using both EEG
      fMRI hemodynamic responses and ESI. A single localization was derived from each
      individual test (EEG-fMRI global maxima [GM]/ESI maximum) and from the
      combination of both maps (EEG-fMRI/ESI spatial intersection). To determine the
      localization accuracy and its predictive performance, the individual and combined
      test localizations were compared to the presumed EZ and to the postsurgical
      outcome. RESULTS: Fifty-two of 53 patients had significant maps: 47 of 53 for EEG
      fMRI, 44 of 53 for ESI, and 34 of 53 for both. The EZ was well characterized in
      29 patients; 26 had an EEG-fMRI GM localization that was correct in 11, 22
      patients had ESI localization that was correct in 17, and 12 patients had
      combined EEG-fMRI and ESI that was correct in 11. Seizure outcome following
      resection was correctly predicted by EEG-fMRI GM in 8 of 20 patients, and by the
      ESI maximum in 13 of 16. The combined EEG-fMRI/ESI region entirely predicted
      outcome in 9 of 9 patients, including 3 with no lesion visible on MRI.
      INTERPRETATION: EEG-fMRI combined with ESI provides a simple unbiased
      localization that may predict surgery better than each individual test, including
      in MRI-negative patients. Ann Neurol 2017;82:278-287.

PMID- 28749545
TI  - Optimization of throughput in semipreparative chiral liquid chromatography using
      stacked injection.
AB  - An interesting mode of chromatography for preparation of pure enantiomers from
      pure samples is the method of stacked injection as a pseudocontinuous procedure.
      Maximum throughput and minimal production costs can be achieved by the use of
      total chiral column length in this mode of chromatography. To maximize sample
      loading, often touching bands of the two enantiomers is automatically achieved.
      Conventional equations show direct correlation between touching-band loadability
      and the selectivity factor of two enantiomers. The important question for one who
      wants to obtain the highest throughput is "How to optimize different factors
      including selectivity, resolution, run time, and loading of the sample in order
      to save time without missing the touching-band resolution?" To answer this
      question, tramadol and propranolol were separated on cellulose 3,5-dimethyl
      phenyl carbamate, as two pure racemic mixtures with low and high solubilities in
      mobile phase, respectively. The mobile phase composition consisted of n-hexane
      solvent with alcohol modifier and diethylamine as the additive. A response
      surface methodology based on central composite design was used to optimize
      separation factors against the main responses. According to the stacked injection
      properties, two processes were investigated for maximizing throughput: one with a
      poorly soluble and another with a highly soluble racemic mixture. For each case,
      different optimization possibilities were inspected. It was revealed that
      resolution is a crucial response for separations of this kind. Peak area and run
      time are two critical parameters in optimization of stacked injection for binary
      mixtures which have low solubility in the mobile phase.

PMID- 28749546
TI  - Familial progressive hyperpigmentation: A family resurvey and ultrastructural
      skin investigation.
AB  - Familial progressive hyperpigmentation (FPH) is an autosomal dominant
      genodermatosis characterized by hyperpigmented patches that increase in size and
      number with age. Since its initial description in an African-American family in
      1971, only a few cases of FPH have been documented. A three-generation family
      with FPH in central China has also been reported. Here, we resurveyed that
      Chinese FPH family for a few unusual features including delayed age of onset and
      noninvolvement of ocular and oral mucosae. Electron microscopic examination of
      skin from the proband of the family showed that there were more melanosomes in
      lesional keratinocytes than in perilesional keratinocytes. Additionally, a large
      number of nonmembrane-bound melanosome complexes were observed in the
      keratinocytes of hyperpigmented areas, whereas all of the melanosomes were
      dispersed in the keratinocytes of normally pigmented areas.

PMID- 28749547
TI  - Comparing the lexical similarity of the triarchic model of psychopathy to
      contemporary models of psychopathy.
AB  - OBJECTIVE: The triarchic model of psychopathy (Patrick, Fowles, & Krueger, 2009)
      posits that psychopathic personality comprises three domains: boldness, meanness,
      and disinhibition. The present study aimed to clarify conceptual overlap between
      contemporary definitions of psychopathy, with particular emphasis given to the
      relevance of boldness (i.e., social dominance, venturesomeness, emotional
      resiliency)-a topic of recent debate. METHOD: Undergraduate students (N = 439)
      compared the lexical similarity of triarchic domains with two contemporary models
      of psychopathy: the Comprehensive Assessment of Psychopathic Personality (CAPP;
      Cooke, Hart, Logan, & Michie, 2012) and the Five-Factor Model of psychopathy
      (FFM; Widiger & Lynam, 1998). RESULTS: From a content validity perspective,
      meanness and disinhibition were lexically similar to both the CAPP and FFM
      psychopathy, whereas boldness was less strongly associated with these models.
      Meanness showed the strongest lexical similarity in comparison with past
      prototypicality ratings of the CAPP and FFM psychopathy. CONCLUSIONS: These
      findings bear implications for defining and comparing conceptualizations of
      psychopathy that underpin its assessment.

PMID- 28749548
TI  - C-MYC-positive relapsed and refractory, diffuse large B-cell lymphoma: Impact of
      additional "hits" and outcomes with subsequent therapy.
AB  - BACKGROUND: The impact of MYC proto-oncogene, basic helix-loop-helix (MYC)
      translocations (with or without additional rearrangements involving the B-cell
      lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival
      in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary
      treatment failure is not well defined. METHODS: This was a multicenter,
      retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in
      patients with DLBCL who failed to achieve complete remission or relapsed within 6
      months after they completed upfront chemoimmunotherapy. RESULTS: The authors
      examined response to salvage therapy, receipt of hematopoietic cell
      transplantation (HCT), and survival outcomes in MYC-negative (n = 120), MYC
      positive single hit (SH) (n = 20), and MYC-positive double hit/triple hit (DH/TH)
      (n = 35) cohorts. The overall response rate in these cohorts to first salvage
      therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%,
      respectively) were comparable between the 3 cohorts. The 2-year overall survival
      rate was 29.9% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and
      9.9% in the MYC-positive DH/TH cohort (P < .001), and no difference was observed
      between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients
      with MYC-positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98
      2.96; P = .06) and those with MYC-positive DH/TH DLBCL (hazard ratio, 2.22; 95%
      confidence interval, 1.41-3.50; P = .001) persisted after adjusting for
      covariates. For patients who underwent autologous HCT, the 2-year overall
      survival rate was 55.4% in the MYC-negative cohort, 0% in the MYC-positive SH
      cohort, and 19.4% in the MYC-positive DH/TH cohort (P < .001). All 4 MYC-positive
      patients who underwent allogeneic HCT relapsed in <4 months. CONCLUSIONS:
      Patients with MYC-positive DLBCL who experience primary treatment failure have
      response rates to similar to those achieved by salvage therapy compared with
      their MYC-negative counterparts, but their survival is dismal irrespective of
      additional "hits" and HCT, representing an unmet medical need. Cancer
      2017;123:4411-8. (c) 2017 American Cancer Society.

PMID- 28749549
TI  - A double-blind, placebo-controlled study of rituximab in patients with stiff
      person syndrome.
AB  - OBJECTIVE: In stiff person syndrome (SPS), an antibody-mediated impaired gamma
      aminobutyric acidergic (GABAergic) neurotransmission is believed to cause muscle
      stiffness and spasms. Most patients improve with GABA-enhancing drugs and
      intravenous immunoglobulin, but some respond poorly and remain disabled. The need
      for more effective therapy prompted a trial with the anti-CD20 monoclonal
      antibody rituximab. METHODS: This was a placebo-controlled randomized trial of
      rituximab (2 biweekly infusions of 1g each). The primary outcome was a change in
      stiffness scores at 6 months. Secondary outcomes were changes in heightened
      sensitivity and quality of life scores. Enrolling 24 patients was calculated to
      detect 50% change in stiffness scores. RESULTS: Randomization was balanced for
      age, sex, disease duration, and glutamic acid decarboxylase autoantibody titers.
      No significant changes were noted at 6 months after treatment in all outcomes.
      Specifically, no differences were noted in the stiffness index, the primary
      outcome, or sensitivity scores, the secondary outcome, at 3 or 6 months. Quality
      of life scores improved significantly (p < 0.01) at 3 months in both groups, but
      not at 6 months, denoting an early placebo effect. Blinded self-assessment rating
      of the overall stiffness for individual patients revealed improvement in 4
      patients in each group. At 6 months, improvement persisted in 1 patient in the
      placebo group versus 3 of 4 in the rituximab group, where these meaningful
      improvements were also captured by video recordings. INTERPRETATION: This is the
      largest controlled trial conducted in SPS patients and demonstrates no
      statistically significant difference in the efficacy measures between rituximab
      and placebo. Rituximab's lack of efficacy could be due to a considerable placebo
      effect; insensitivity of scales to quantify stiffness, especially in the less
      severely affected patients; or drug effectiveness in only a small patient subset.
      Ann Neurol 2017;82:271-277.

PMID- 28749550
TI  - Combined resistance and endurance training at a moderate-to-high intensity
      improves physical condition and quality of life in liver transplant patients.
AB  - Although currently moderate and high intensity concurrent physical exercise is
      prescribed in populations with special needs due to its greater effect on
      physical condition and health-related quality of life (HRQOL), there are no data
      in the liver transplantation (LT) setting. The aim of this study is to evaluate
      changes in maximal strength, aerobic capacity, body composition, liver function,
      and HRQOL in LT patients after a moderate-to-high intensity combined resistance
      endurance training. Six months after LT, 54 patients were randomized into 2
      groups: intervention group (IG) and control group (CG). A total of 50 patients
      completed the study with repeat testing at 6 and 12 months after LT. The IG
      completed a 6-month exercise training program, consisting of exercising 2 days
      for 24 weeks in the hospital facilities, whereas the CG followed usual care
      recommendations. Patients completed a 5-multijoint exercise circuit with elastic
      bands involving the major muscle groups. The effects of the concurrent training
      program on maximal oxygen consumption, overall and regional maximal strength,
      body composition, liver function, and HRQOL were analyzed. The IG showed a
      significant improvement (P < 0.05) in outcome measurements compared with the CG
      in aerobic capacity, hip extension, elbow flexion, overall maximal strength,
      physical functioning, and vitality of HRQOL, whereas no changes were observed in
      body composition and liver function tests. In conclusion, this is the first study
      that combines supervised resistance and aerobic training performed at moderate-to
      high intensity in LT recipients. It results in significant improvements in
      aerobic capacity, maximal strength, and HRQOL. Liver Transplantation 23 1273-1281
      2017 AASLD.

PMID- 28749551
TI  - A novel allele HLA-B*27:149 identified by sequence-based typing in a Chinese
      individual.
AB  - HLA-B*27:149 differs from HLA-B*27:04:01 (488C->T, exon 3, A139V).

PMID- 28749552
TI  - The eigenvalue problem in phase space.
AB  - We formulate the standard quantum mechanical eigenvalue problem in quantum phase
      space. The equation obtained involves the c-function that corresponds to the
      quantum operator. We use the Wigner distribution for the phase space function. We
      argue that the phase space eigenvalue equation obtained has, in addition to the
      proper solutions, improper solutions. That is, solutions for which no wave
      function exists which could generate the distribution. We discuss the conditions
      for ascertaining whether a position momentum function is a proper phase space
      distribution. We call these conditions psi-representability conditions, and show
      that if these conditions are imposed, one extracts the correct phase space
      eigenfunctions. We also derive the phase space eigenvalue equation for arbitrary
      phase space distributions functions. (c) 2017 Wiley Periodicals, Inc.

PMID- 28749553
TI  - Myelopathy in Behcet's disease: The Bagel Sign.
AB  - OBJECTIVE: To describe the clinical and distinctive imaging features of
      myelopathy associated with Behcet's disease (BD). METHODS: We evaluated the
      records of patients meeting the following criteria: (1) fulfillment of the
      International Study Group criteria for BD; (2) clinically suggestive of
      myelopathy; (3) simultaneous spinal cord and brain magnetic resonance images
      (MRIs) within 1 month of acute worsening of myelopathy; and (4) follow-up
      duration >= 1 year after initial MRI evaluation. Patients not fulfilling all
      inclusion criteria and having MRIs with poor quality or missing sequences were
      excluded. RESULTS: In 11 patients (9 men, 2 women), we studied 14 MRIs during
      distinct myelopathy episodes and nine follow-up MRIs. Two distinct MRI patterns
      of spinal cord involvement were described according to T2-weighted (T2W) axial
      images: (1) "Bagel Sign" pattern: a central lesion with hypointense core and
      hyperintense rim with or without contrast enhancement; and (2) "Motor Neuron"
      pattern: a symmetric involvement of the anterior horn cells. Bagel Sign was
      present in 13 of 14 myelopathy episodes whereas Motor Neuron pattern was observed
      in 1 of 14 MRIs. Of the 13 MRIs with Bagel Sign long myelopathy (n = 9), both
      long and short myelopathy (n = 2) and short myelopathy (n = 2) was observed. All
      patterns cleared with some residual lesions after steroid use and
      immunomodulation with associated clinical recovery in patients. INTERPRETATION:
      The signal characteristics of the Bagel Sign potentially represent venous
      engorgement and/or acute blood products within the spinal cord. To our knowledge,
      Bagel Sign has not been observed in other forms of longitudinal myelopathy
      outside of BD, including neuromyelitis optica. Ann Neurol 2017;82:288-298.

PMID- 28749554
TI  - High-Energy-Resolution X-ray Absorption Spectroscopy for Identification of
      Reactive Surface Species on Supported Single-Site Iridium Catalysts.
AB  - We report high-energy-resolution X-ray absorption spectroscopy detection of
      ethylene and CO ligands adsorbed on catalytically active iridium centers isolated
      on zeolite HY and on MgO supports. The data are supported by density functional
      theory and FEFF X-ray absorption near-edge modelling, together with infrared (IR)
      spectra. The results demonstrate that high-energy-resolution X-ray absorption
      spectra near the iridium LIII (2p3/2 ) edge provide clearly ascribable,
      distinctive signatures of the ethylene and CO ligands and illustrate effects of
      supports and other ligands. This X-ray absorption technique is markedly more
      sensitive than conventional IR spectroscopy for characterizing surface
      intermediates, and it is applicable to samples having low metal loadings and in
      reactive atmospheres and is expected to have an increasing role in catalysis
      research by facilitating the determination of mechanisms of solid-catalyzed
      reactions through identification of reaction intermediates in working catalysts.

PMID- 28749555
TI  - Response to comment on "Primary sources and toxicity of PAHs in Milwaukee-area
      streambed sediments"-The authors' reply.

PMID- 28749556
TI  - Global Spotlights are papers selected by editors published in peer-reviewed
      journals that may be more regionally specific or appearing in languages other
      than English.

PMID- 28749558
TI  - Erratum.

PMID- 28749557
TI  - Letter commenting on "Primary sources and toxicity of PAHs in Milwaukee-area
      streambed sediment"-To the editor.

PMID- 28749559
TI  - Recombinant covalently closed circular DNA of hepatitis B virus induces long-term
      viral persistence with chronic hepatitis in a mouse model.
AB  - : Covalently closed circular DNA of hepatitis B virus (HBV) is critical for viral
      persistence in vivo. We recently reported a technique involving recombinant
      covalently closed circular DNA (rcccDNA) of HBV by site-specific DNA
      recombination. Using hydrodynamic injection, rcccDNA induces a temporarily
      prolonged HBV antigenemia in immunocompetent mice, similar to acute resolving HBV
      infection. In this study, we simulated the pathophysiological impact of chronic
      hepatitis to reproduce rcccDNA persistence in mouse models. We showed that
      rcccDNA achieved long-lasting persistence in the presence of a compromised immune
      response or when transcriptional activity was repressed. To closely mimic chronic
      hepatitis, we used a replication-defective recombinant adenoviral vector to
      deliver rcccDNA to the liver, which led to prominent HBV persistence throughout
      the experiment duration (>62 weeks) in transgenic mice expressing Cre recombinase
      under the albumin promoter. A sustained necroinflammatory response and fibrosis
      were identified in mouse livers, with dysplastic lesions commonly seen during the
      late stage of viral persistence, analogous to the progressive pathology of
      clinical chronic hepatitis. CONCLUSION: rcccDNA was intrinsically stable in vivo,
      enabling long-term persistence in the context of chronic hepatitis, and viral
      persistence, in turn, may promote progression of chronic liver disease; our study
      also presented a surrogate model of HBV cccDNA persistence in mice that could
      advance our understanding of the pathogenesis of chronic hepatitis B. (Hepatology
      2018;67:56-70).

PMID- 28749560
TI  - Arbuscular mycorrhizal fungi alter the content and composition of secondary
      metabolites in Bituminaria bituminosa L.
AB  - Secondary metabolites may be affected by arbuscular mycorrhizal fungi (AMF),
      which are beneficial symbionts associated with the roots of most plant species.
      Bituminaria bituminosa (L.) C.H.Stirt is known as a source of several
      phytochemicals and therefore used in folk medicine as a vulnerary, cicatrising,
      disinfectant agent. Characteristic metabolites found in B. bituminosa are
      furanocoumarins and pterocarpans, which are used in cosmetics and as
      chemotherapeutic agents. Here we address the question whether AMF inoculation
      might affect positively the synthesis of these phytochemicals. B. bituminosa
      plants were inoculated with different AMF and several metabolites were assessed
      during full vegetative stage and flowering phase. Pigments (chlorophylls and
      carotenoids), polyphenols and flavonoids were spectrophotometrically determined;
      specific isoflavones (genistein), furanocoumarins (psoralene and angelicin),
      pterocarpans (bitucarpin A and erybraedin C) and plicatin B were assessed with
      HPLC; leaf volatile organic compounds were analysed using SPME and identified by
      GC-MS. During the vegetative stage, the inoculated plants had a high amount of
      furanocoumarins (angelicin and psoralen) and pterocarpans (erybraedin C and
      bitucarpin A). The analysis of volatile organic compounds of inoculated plants
      showed different chemical composition compared with non-mycorrhizal plants. Given
      the important potential role played by furanocoumarins and pterocarpans in the
      pharmaceutical industry, AMF inoculation of B. bituminosa plants may represent a
      suitable biotechnological tool to obtain higher amounts of such metabolites for
      pharmaceutical and medicinal purposes.

PMID- 28749561
TI  - Trends in prevalence of leisure time physical activity and inactivity: results
      from Australian National Health Surveys 1989 to 2011.
AB  - OBJECTIVE: To examine trends in leisure time physical activity and inactivity in
      Australians aged 15 years or older from 1989 to 2011. METHOD: We used data from
      six Australian National Health Surveys conducted from 1989/90 to 2011/12 in which
      physical activity was assessed using comparable questions. Analyses examined
      trends in the prevalence of sufficient physical activity (>=150 minutes/week
      moderate-to-vigorous physical activity) and of inactivity (<30 minutes/week
      moderate-to-vigorous physical activity). RESULTS: The proportion of sufficiently
      active adults was 39.2% in 1989 and 40.7% in 2011 with an overall declining trend
      of 0.2% per year (p=0.012). The prevalence of inactivity was 38.7% in 1989 and
      37.3% in 2011; the overall time trend by year was stable (OR=0.999, p=0.242). In
      women, sufficient physical activity decreased by 0.3% per year from 35.5% in 1989
      (p=0.025); inactivity increased from 39.5% by 0.3% per year (p=0.004). In men,
      sufficient physical activity prevalence was 43.1% in 1989 with a steady trend;
      inactivity decreased from 37.9% by 0.5% per year (p<0.0001). CONCLUSIONS: The
      prevalence of sufficient physical activity remains low and inactivity high. Women
      appear to be a key target group for intervention. Public health efforts have been
      ineffective over two decades for improving physical activity among Australian
      adults. Implications for public health: This research supports calls for a
      national physical activity action plan given the multitude of benefits from
      sufficient physical activity. Maintenance of consistent physical activity
      questions in future National Health Surveys will facilitate long term tracking of
      physical activity levels in the Australian population.

PMID- 28749562
TI  - School-based systems change for obesity prevention in adolescents: outcomes of
      the Australian Capital Territory 'It's Your Move!'
AB  - OBJECTIVE: The Australian Capital Territory 'It's Your Move!' (ACT-IYM) was a
      three-year (2012-2014) systems intervention to prevent obesity among adolescents.
      METHODS: The ACT-IYM project involved three intervention schools and three
      comparison schools and targeted secondary students aged 12-16 years. The
      intervention consisted of multiple initiatives at individual, community, and
      school policy level to support healthier nutrition and physical activity.
      Intervention school-specific objectives related to increasing active transport,
      increasing time spent physically active at school, and supporting mental
      wellbeing. Data were collected in 2012 and 2014 from 656 students. Anthropometric
      data were objectively measured and behavioural data self-reported. RESULTS:
      Proportions of overweight or obesity were similar over time within the
      intervention (24.5% baseline and 22.8% follow-up) and comparison groups (31.8%
      baseline and 30.6% follow-up). Within schools, two of three the intervention
      schools showed a significant decrease in the prevalence of overweight and obesity
      (p<0.05). CONCLUSIONS: There was some evidence of effectiveness of the systems
      approach to preventing obesity among adolescents. Implications for public health:
      The incorporation of systems thinking has been touted as the next stage in
      obesity prevention and public health more broadly. These findings demonstrate
      that the use of systems methods can be effective on a small scale.

PMID- 28749563
TI  - A Probabilistic Framework for Risk Analysis of Widespread Flood Events: A Proof
      of-Concept Study.
AB  - This article presents a flood risk analysis model that considers the spatially
      heterogeneous nature of flood events. The basic concept of this approach is to
      generate a large sample of flood events that can be regarded as temporal
      extrapolation of flood events. These are combined with cumulative flood impact
      indicators, such as building damages, to finally derive time series of damages
      for risk estimation. Therefore, a multivariate modeling procedure that is able to
      take into account the spatial characteristics of flooding, the regionalization
      method top-kriging, and three different impact indicators are combined in a model
      chain. Eventually, the expected annual flood impact (e.g., expected annual
      damages) and the flood impact associated with a low probability of occurrence are
      determined for a study area. The risk model has the potential to augment the
      understanding of flood risk in a region and thereby contribute to enhanced risk
      management of, for example, risk analysts and policymakers or insurance
      companies. The modeling framework was successfully applied in a proof-of-concept
      exercise in Vorarlberg (Austria). The results of the case study show that risk
      analysis has to be based on spatially heterogeneous flood events in order to
      estimate flood risk adequately.

PMID- 28749564
TI  - Impact of sustained virologic response with direct-acting antiviral treatment on
      mortality in patients with advanced liver disease.
AB  - : The impact of sustained virologic response (SVR) on mortality after direct
      acting antiviral treatment is not well documented. This study evaluated the
      impact of direct-acting antiviral-induced SVR on all-cause mortality and on
      incident hepatocellular carcinoma (HCC) in 15,059 hepatitis C virus-infected
      patients with advanced liver disease defined by a FIB-4 >3.25. Overall, 1,067
      patients did not achieve SVR (no SVR) and 13,992 patients achieved SVR. In a mean
      follow-up period of approximately 1.6 years, 195 no SVR patients and 598 SVR
      patients died. Mortality rates were 12.3 deaths/100 patient years of follow-up
      for no SVR patients and 2.6 deaths/100 patient years for SVR patients, a 78.9%
      reduction (P < 0.001). Among patients without a prior diagnosis of HCC, 140 no
      SVR patients and 397 SVR patients were diagnosed with incident HCC. HCC rates
      were 11.5 HCCs/100 patient years for no SVR patients and 1.9 HCCs/100 patient
      years for SVR patients, an 83.5% reduction (P < 0.001). In multivariable Cox
      proportional hazard models controlling for baseline demographics, clinical
      characteristics, and comorbidities, SVR was independently associated with reduced
      risk of death compared to no SVR (hazard ratio, 0.26; 95% confidence interval,
      0.22-0.31; P < 0.001). A history of decompensated liver disease (hazard ratio,
      1.57; 95% confidence interval, 1.34-1.83; P < 0.001) and decreased albumin
      (hazard ratio, 2.70 per 1 g/dL decrease; 95% confidence interval, 2.38-3.12; P <
      0.001) were independently associated with increased risk of death. CONCLUSION:
      Those achieving SVR after direct-acting antiviral treatment had significantly
      lower all-cause mortality and lower incident HCC rates than those who did not
      achieve SVR. (Hepatology 2017).

PMID- 28749565
TI  - Melatonin suppresses platelet activation and function against cardiac
      ischemia/reperfusion injury via PPARgamma/FUNDC1/mitophagy pathways.
AB  - Platelet activation is a major (patho-) physiological mechanism that underlies
      ischemia/reperfusion (I/R) injury. In this study, we explored the molecular
      signals for platelet hyperactivity and investigated the beneficial effects of
      melatonin on platelet reactivity in response to I/R injury. After reperfusion,
      peroxisome proliferator-activated receptor gamma (PPARgamma) was progressively
      downregulated in patients with acute myocardial infarction undergoing coronary
      artery bypass grafting (CABG) surgery and in mice with I/R injury model. Loss of
      PPARgamma was closely associated with FUN14 domain containing 1 (FUNDC1)
      dephosphorylation and mitophagy activation, leading to increased mitochondrial
      electron transport chain complex (ETC.) activity, enhanced mitochondrial
      respiratory function, and elevated ATP production. The improved mitochondrial
      function strongly contributed to platelet aggregation, spreading, expression of P
      selectin, and final formation of micro-thromboses, eventually resulting in
      myocardial dysfunction and microvascular structural destruction. However,
      melatonin powerfully suppressed platelet activation via restoration of the
      PPARgamma content in platelets, which subsequently blocked FUNDC1-required
      mitophagy, mitochondrial energy production, platelet hyperactivity, and cardiac
      I/R injury. In contrast, genetic ablation of PPARgamma in platelet abolished the
      beneficial effects of melatonin on mitophagy, mitochondrial ATP supply, and
      platelet activation. Our results lay the foundation for the molecular mechanism
      of platelet activation in response to I/R injury and highlight that the
      manipulation of the PPARgamma/FUNDC1/mitophagy pathway by melatonin could be a
      novel strategy for cardioprotection in the setting of cardiac I/R injury.

PMID- 28749566
TI  - The facilitators and barriers of physical activity among Aboriginal and Torres
      Strait Islander regional sport participants.
AB  - BACKGROUND: Disparities in health perspectives between Indigenous and non
      Indigenous populations are major concerns in many of the world's well-developed
      nations. Indigenous populations are largely less healthy, more prone to chronic
      diseases, and have an earlier overall mortality than non-Indigenous populations.
      Low levels of physical activity (PA) contribute to the high levels of disease in
      Indigenous Australians. METHOD: Qualitative analysis of structured one-on-one
      interviews discussing PA in a regional setting. Participants were 12 Indigenous
      Australian adults, and 12 non-Indigenous Australian adults matched on age, sex,
      and basketball division. RESULTS: Most participants reported engaging in regular
      exercise; however, the Indigenous group reported more barriers to PA. These
      factors included cost, time management and environmental constraints. The
      physical facilitators identified by our Indigenous sample included social
      support, intrinsic motivation and role modelling. CONCLUSION: Findings describe
      individual and external factors that promote or constraint PA as reported by
      Indigenous Australian adults. Results indicate that Indigenous people face
      specific barriers to PA when compared to a non-Indigenous sample. Implications
      for public health: This study is the first to compare the perspective of
      Indigenous Australians to a matched group of non-Indigenous Australians and
      provides useful knowledge to develop public health programs based on culturally
      sensitive data.

PMID- 28749567
TI  - Ab Initio energetics of Si?O bond cleavage.
AB  - A multilevel approach that combines high-level ab initio quantum chemical methods
      applied to a molecular model of a single, strain-free Si?O?Si bridge has been
      used to derive accurate energetics for Si?O bond cleavage. The calculated Si?O
      bond dissociation energy and the activation energy for water-assisted Si?O bond
      cleavage of 624 and 163 kJ mol-1 , respectively, are in excellent agreement with
      values derived recently from experimental data. In addition, the activation
      energy for H2 O-assisted Si?O bond cleavage is found virtually independent of the
      amount of water molecules in the vicinity of the reaction site. The estimated
      reaction energy for this process including zero-point vibrational contribution is
      in the range of -5 to 19 kJ mol-1 . (c) 2017 Wiley Periodicals, Inc.

PMID- 28749568
TI  - Experts' views regarding Australian school-leavers' knowledge of nutrition and
      food systems.
AB  - OBJECTIVE: To explore Australian experts' views regarding strengths and gaps in
      school-leavers' knowledge of nutrition and food systems ( N&FS) and factors that
      influence that knowledge. METHOD: Semi-structured interviews were conducted with
      21 highly experienced food-related experts in Australia. Qualitative data were
      analysed thematically using Attride-Stirling's thematic network framework.
      RESULTS: Two global themes and several organising themes were identified. The
      first global theme, 'structural curriculum-based problems', emerged from three
      organising themes of: inconsistencies in provided food education programs at
      schools in Australia; insufficient coverage of food-related skills and food
      systems topics in school curricula; and the lack of trained school teachers. The
      second global theme, 'insufficient levels of school-leavers knowledge of N&FS ',
      was generated from four organising themes, which together described Australian
      school-leavers' poor knowledge of N&FS more broadly and knowledge translation
      problem for everyday practices. CONCLUSION: Study findings identified key
      problems relating to current school-based N&FS education programs in Australia
      and reported knowledge gaps in relation to N&FS among Australian school-leavers.
      IMPLICATIONS: These findings provide important guidance for N&FS curriculum
      development, to clearly articulate broadly-based N&FS knowledge acquisition in
      curriculum policy and education documents for Australian schools.

PMID- 28749569
TI  - Is Zika virus a potential threat to the Australian Blood Supply?

PMID- 28749571
TI  - L-ornithine L-aspartate in bouts of overt hepatic encephalopathy.
AB  - : High-quality data on the efficacy of L-ornithine L-aspartate (LOLA) in patients
      with cirrhosis and bouts of overt hepatic encephalopathy (OHE) are missing. We
      evaluated the efficacy of intravenous LOLA in the reversal of bouts of OHE in
      patients with cirrhosis. In this prospective, double-blind, randomized, placebo
      controlled trial conducted at two tertiary care institutes in India, 370 patients
      with cirrhosis and bouts of OHE were screened. After exclusion, 193 (52.16%)
      patients were randomized to receive either intravenous infusions of LOLA (n =
      98), 30 g daily, or placebo (n = 95) for 5 days. Standard of care treatment
      (including lactulose and ceftriaxone) was given in both groups. Randomization was
      done centrally (http://www.sealedenvelope.com/). All study personnel were blinded
      to the treatment assignment. Fasting venous ammonia levels were estimated daily
      from 0 to 5 days. Serum tumor necrosis factor-alpha, interleukins, hemogram, and
      liver and renal function tests were performed at days 0 and 5. Primary outcome
      was mental state grade at day 5 of treatment. The grade of OHE was significantly
      lower in the LOLA group (compared to placebo) on days 1-4 but not on day 5. The
      mean time taken for recovery was lower in the LOLA group compared to the placebo
      group (1.92 +/- 0.93 versus 2.50 +/- 1.03 days, P = 0.002; 95% confidence
      interval -0.852 to -0.202). Venous ammonia at day 5 and length of hospital stay
      were significantly lower in the LOLA group. No significant difference in
      interleukins was seen between the groups. CONCLUSION: In patients with bouts of
      OHE, intravenous LOLA (as an add-on therapy to lactulose and ceftriaxone)
      significantly improves the grade of OHE over days 1-4, but not on day 5, and
      decreases venous ammonia, time of recovery, and length of hospital stay.
      (Hepatology 2017).

PMID- 28749570
TI  - Hepatocyte-derived exosomes promote T follicular regulatory cell expansion during
      hepatitis C virus infection.
AB  - : Hepatitis C virus (HCV) is a global health concern that can cause severe liver
      disease, such as cirrhosis and hepatocellular carcinoma. Control of HCV requires
      vigorous T-cell responses, yet CD4+ T cells in chronic HCV patients are
      dysfunctional. T follicular regulatory (Tfr) cells are a subset of regulatory T
      cells that suppress T follicular helper (Tfh) cells and the generation of high
      affinity antibody-producing B cells. In this study, we examined the accumulation
      of Tfr cells in the liver compartment during chronic HCV infection and defined
      the cellular and molecular mechanisms underlying their expansion. Our analysis
      revealed a substantial population of Tfr cells in livers of chronic HCV patients
      that is absent in liver tissues from nonviral hepatitis or healthy subjects.
      Coculture of PBMCs from healthy subjects with HCV-infected hepatoma cells
      resulted in preferential expansion of circulating Tfr cells, leading to
      suppression of Tfh cells. Additionally, coculture of tonsillar cells with
      infected hepatoma cells lead to an expansion of germinal center Tfr. Notably,
      expansion was mediated by transforming growth factor beta (TGF-beta)-containing
      exosomes released from HCV-infected hepatocytes given that blockade of exosome
      associated TGF-beta or inhibition of exosome release abrogated Tfr expansion.
      CONCLUSION: These results show that liver-derived exosomes play a pivotal role in
      the accumulation of Tfr cells, likely leading to suppression of Tfh responses in
      HCV-infected patients. Our study identifies a novel pathway in which HCV
      infection in hepatocytes exacerbates Tfr cell responses to subvert antiviral
      immunity. (Hepatology 2018;67:71-85).

PMID- 28749572
TI  - New Zealand adolescents' discouragement of smoking among their peers.
AB  - OBJECTIVE: This study examines the extent to which young people are acting as
      'agents of change' in discouraging smoking among their peers. METHODS: This study
      used data from a survey of 2,919 New Zealand secondary school students who
      participated in the 2014 national Youth In-depth Survey. Relevant questions were
      used to assess the extent to which students engaged in behaviours to discourage
      or promote smoking among their peers. RESULTS: About half of all students
      reported some form of behaviour discouraging others from smoking, while only one
      in ten reported encouraging smoking. Discouragement was associated with non
      smoking or lower levels of smoking, having more friends who smoked, and exposure
      to more health promotion messages about not smoking. Maori and Pacific young
      people also reported more discouraging behaviours. CONCLUSIONS: The results
      highlight the positive impact that young people can have on discouraging smoking
      among their peers. Implications for public health: The findings of this study
      point to encouraging and training young people as 'agents of change' to spread
      the smokefree message.

PMID- 28749573
TI  - Interleukin-6/STAT3 signaling as a promising target to improve the efficacy of
      cancer immunotherapy.
AB  - Overcoming the immunosuppressive state in tumor microenvironments is a critical
      issue for improving the efficacy of cancer immunotherapy. Interleukin (IL)-6, a
      pleiotropic cytokine, is highly produced in the tumor-bearing host. Previous
      studies have indicated that IL-6 suppresses the antigen presentation ability of
      dendritic cells (DC) through activation of signal transducer and activator of
      transcription 3 (STAT3). Thus, we focused on the precise effect of the IL-6/STAT3
      signaling cascade on human DC and the subsequent induction of antitumor T cell
      immune responses. Tumor-infiltrating CD11b+ CD11c+ cells isolated from colorectal
      cancer tissues showed strong induction of the IL-6 gene, downregulated surface
      expression of human leukocyte antigen (HLA)-DR, and an attenuated T cell
      stimulating ability compared with those from peripheral blood mononuclear cells,
      suggesting that the tumor microenvironment suppresses antitumor effector cells.
      In vitro experiments revealed that IL-6-mediated STAT3 activation reduced surface
      expression of HLA-DR on CD14+ monocyte-derived DC. Moreover, we confirmed that
      cyclooxygenase 2, lysosome protease and arginase activities were involved in the
      IL-6-mediated downregulation of the surface expression levels of HLA class II on
      human DC. These findings suggest that IL-6-mediated STAT3 activation in the tumor
      microenvironment inhibits functional maturation of DC to activate effector T
      cells, blocking introduction of antitumor immunity in cancers. Therefore, we
      propose in this review that blockade of the IL-6/STAT3 signaling pathway and
      target molecules in DC may be a promising strategy to improve the efficacy of
      immunotherapies for cancer patients.

PMID- 28749575
TI  - Comparing pairwise-additive and many-body generalized Born models for acid/base
      calculations and protein design.
AB  - Generalized Born (GB) solvent models are common in acid/base calculations and
      protein design. With GB, the interaction between a pair of solute atoms depends
      on the shape of the protein/solvent boundary and, therefore, the positions of all
      solute atoms, so that GB is a many-body potential. For compute-intensive
      applications, the model is often simplified further, by introducing a mean,
      native-like protein/solvent boundary, which removes the many-body property. We
      investigate a method for both acid/base calculations and protein design that uses
      Monte Carlo simulations in which side chains can explore rotamers, bind/release
      protons, or mutate. The fluctuating protein/solvent dielectric boundary is
      treated in a way that is numerically exact (within the GB framework), in contrast
      to a mean boundary. Its originality is that it captures the many-body character
      while retaining the residue-pairwise complexity given by a fixed boundary. The
      method is implemented in the Proteus protein design software. It yields a slight
      but systematic improvement for acid/base constants in nine proteins and a
      significant improvement for the computational design of three PDZ domains. It
      eliminates a source of model uncertainty, which will facilitate the analysis of
      other model limitations. (c) 2017 Wiley Periodicals, Inc.

PMID- 28749574
TI  - Design, Synthesis, Pharmacological Evaluation and Docking Studies of GluN2B
      Selective NMDA Receptor Antagonists with a Benzo[7]annulen-7-amine Scaffold.
AB  - Antagonists that selectively target GluN2B-subunit-containing N-methyl-d
      aspartate (NMDA) receptors are of major interest for the treatment of various
      neurological disorders. In this study, relationships between variously
      substituted benzo[7]annulen-7-amines and their GluN2B affinity were investigated.
      2-Nitro-5,6,8,9-tetrahydrobenzo[7]annulen-7-one (8) represents the central
      building block for the introduction of various substituents at the 2-position and
      various 7-amino moieties. N-(3-Phenylpropyl)-6,7,8,9-tetrahydro-5H
      benzo[7]annulen-7-amines with a 2-NO2 (7 c), 2-Cl (15 c), or 2-OBn group (22 c)
      show very high GluN2B affinity (Ki =1.6-3.6 nm). Docking studies revealed the
      same binding poses for benzo[7]annulen-7-amines and ifenprodil at the interface
      of GluN1b and GluN2B subunits. The large 2-OBn moiety of 22 c occupies a
      previously unrecognized subpocket, which explains its high GluN2B affinity (Ki
      =3.6 nm). In two-electrode voltage clamp experiments and cytoprotection assays,
      the high-affinity GluN2B ligands 7 c, 15 c, and 22 c could not inhibit the
      glutamate-/glycine-evoked current and cytotoxic effects. However, the analogous
      phenols 16 c ((3-phenylpropyl)amino moiety) and 16 d ((4-phenylbutyl)amino
      moiety) with 10-fold lower GluN2B affinity (Ki =28 and 21 nm, respectively)
      showed promising inhibition of glutamate-/glycine-evoked effects in both assays.
      The presence of a phenolic hydroxy group seems to be essential for inducing
      conformational changes of the receptor protein, which finally results in closure
      of the ion conduction pathway.

PMID- 28749576
TI  - Review of the current medical literature and assessment of current utilization
      patterns regarding mismatch repair protein immunohistochemistry in cutaneous Muir
      Torre syndrome-associated neoplasms.
AB  - Muir-Torre syndrome is a clinical variant of Lynch syndrome defined by the
      synchronous or metachronous occurrence of at least one sebaceous neoplasm and at
      least one Lynch syndrome-related internal cancer. Although screening guidelines
      for patients with colorectal carcinomas have been established, screening
      guidelines for cutaneous Muir-Torre associated neoplasms are not currently
      available. As such, we reviewed the current evidence for the use of MLH1, MSH2,
      MSH6 and PMS2 immunohistochemistry when cutaneous Muir-Torre associated neoplasms
      are encountered. We identified weak to moderate support overall for the global
      use of these assays, with some evidence suggesting a tailored approach using
      clinical parameters as an adjunct. We also assessed the current utilization
      patterns of attendees of the American Society of Dermatopathology Annual Meeting
      (Chicago, 2016). We found that 91% of respondents utilize mismatch repair
      immunohistochemistry, with the majority utilizing these tests only when requested
      by the submitting clinician.

PMID- 28749577
TI  - Prevalence and determinants of antibiotic exposure in infants: A population
      derived Australian birth cohort study.
AB  - AIM: The aim of this study was to describe antibiotic exposure in Australian
      infants during the first year of life, focusing on antibiotic class, indication,
      risk factors associated with exposure and comparison with international
      counterparts. METHODS: The Barwon Infant Study is a birth cohort study (n = 1074)
      with an unselected antenatal sampling frame from a large regional centre in
      Victoria, Australia. Longitudinal data on infection and medication were collected
      at 1, 3, 6, 9 and 12 months by parental questionnaire and from general
      practitioner and hospital records. Predictors of questionnaire non-completion
      were identified. A total of 660 infants with complete serial data were
      comprehensively examined. Antibiotic exposure was calculated as (i) antibiotic
      prescriptions and (ii) antibiotic days-exposed per person-year. RESULTS: Mean
      antibiotic prescription rate was 0.92 prescriptions (95% confidence interval
      (CI), 0.83-1.02) per person-year, with the highest rates in those aged <1 month
      (1.50 (95% CI, 1.09-1.91) per person-year). A total of 50.0% of infants were
      exposed to at least one antibiotic in their first year of life. Increasing number
      of siblings was associated with increased antibiotic exposure. Penicillin with
      extended spectrum (365 of 661 antibiotic prescriptions, 52.6%) and cephalosporins
      (12.0%) were the most frequently prescribed antibiotics. One fifth of antibiotics
      were prescribed for respiratory tract infections and bronchiolitis. CONCLUSION:
      Australian infants in this large population-based study are exposed to
      considerably more antibiotics than the majority of their international
      counterparts. Interventions aimed at addressing avoidable prescribing by medical
      practitioners and modifiable risk factors associated with antibiotic exposure may
      reduce antibiotic use.

PMID- 28749578
TI  - A descriptive study of intentional self-poisoning from New Zealand national
      registry data.
AB  - OBJECTIVE: Understanding which population groups intentionally poison themselves
      by overdose and which substances are used are key to developing prevention
      efforts for such injuries. This paper uses Ministry of Health (MOH) data to
      explore the demographic characteristics of those who intentionally self-poison
      and the substances used, identifies limitations of existing data collections and
      makes recommendations for the future. METHODS: MOH mortality data from 2000 to
      2012, and public hospital presentation data from 2000-2014 of cases of
      intentional self-poisoning (ISP), and poisoning of undetermined intent (UDP),
      were examined. RESULTS: Men were more at risk of fatal intentional poisonings,
      while young women and people from deprived areas were predominant in hospital
      presentations for ISP and UDP. While ICD-10 categories were available, there was
      limited information in the majority of MOH data about specific substances used in
      the poisonings. CONCLUSIONS: The current format of MOH data indicates that
      developing interventions to help young people and those living in deprived areas
      may be useful. Finding specific solutions is challenging when only limited
      nationwide substance-specific poisoning information is available. Implications
      for public health: Including specific substances in national data collections is
      important for addressing the public health challenge of intentional overdose
      morbidity and mortality.

PMID- 28749579
TI  - A new type of neurons for machine learning.
AB  - In machine learning, an artificial neural network is the mainstream approach.
      Such a network consists of many neurons. These neurons are of the same type
      characterized by the 2 features: (1) an inner product of an input vector and a
      matching weighting vector of trainable parameters and (2) a nonlinear excitation
      function. Here, we investigate the possibility of replacing the inner product
      with a quadratic function of the input vector, thereby upgrading the first-order
      neuron to the second-order neuron, empowering individual neurons and facilitating
      the optimization of neural networks. Also, numerical examples are provided to
      illustrate the feasibility and merits of the second-order neurons. Finally,
      further topics are discussed.

PMID- 28749580
TI  - Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's
      Disease Clinical Trials: A Disease Progression Modeling Analysis.
AB  - Given the recognition that disease-modifying therapies should focus on earlier
      Parkinson's disease stages, trial enrollment based purely on clinical criteria
      poses significant challenges. The goal herein was to determine the utility of
      dopamine transporter neuroimaging as an enrichment biomarker in early motor
      Parkinson's disease clinical trials. Patient-level longitudinal data of 672
      subjects with early-stage Parkinson's disease in the Parkinson's Progression
      Markers Initiative (PPMI) observational study and the Parkinson Research
      Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear
      mixed-effects model analysis. The rate of worsening in the motor scores between
      subjects with or without a scan without evidence of dopamine transporter deficit
      was different both statistically and clinically. The average difference in the
      change from baseline of motor scores at 24 months between biomarker statuses was 
      3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter
      imaging could identify subjects with a steeper worsening of the motor scores,
      allowing trial enrichment and 24% reduction of sample size.

PMID- 28749581
TI  - Prediction of Transporter-Mediated Drug-Drug Interactions for Baricitinib.
AB  - Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, undergoes active
      renal tubular secretion. Baricitinib was not predicted to inhibit hepatic and
      renal uptake and efflux drug transporters, based on the ratio of the unbound
      maximum eliminating-organ inlet concentration and the in vitro half-maximal
      inhibitory concentrations (IC50 ). In vitro, baricitinib was a substrate for
      organic anion transporter (OAT)3, multidrug and toxin extrusion protein (MATE)2
      K, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP).
      Probenecid, a strong OAT3 inhibitor, increased the area under the concentration
      time curve from time zero to infinity (AUC[0-infinity] ) of baricitinib by
      twofold and decreased renal clearance to 69% of control in healthy subjects.
      Physiologically based pharmacokinetic (PBPK) modeling reproduced the renal
      clearance of baricitinib and the inhibitory effect of probenecid using the in
      vitro IC50 value of 4.4 MUM. Using ibuprofen and diclofenac in vitro IC50 values
      of 4.4 and 3.8 MUM toward OAT3, 1.2 and 1.0 AUC(0-infinity) ratios of baricitinib
      were predicted. These predictions suggest clinically relevant drug-drug
      interactions (DDIs) with ibuprofen and diclofenac are unlikely.

PMID- 28749582
TI  - Is periodontitis associated with halitosis? A systematic review and meta
      regression analysis.
AB  - AIM: To systematically review the literature in order to investigate a potential
      association between periodontitis and halitosis. METHODS: Electronic searches
      were performed in four different databases: PubMed, Scopus, Web of Science and
      Scielo. Population-based observational studies that tested the association
      between periodontitis and halitosis were included. Additionally, meta-analysis,
      meta-regression and subgroup analyses were performed to synthesize the evidence.
      RESULTS: A total of 1,107 articles were identified in electronic searches; out of
      which, five were included within the meta-analysis. Pooled estimates revealed
      that individuals with periodontitis presented 3.16 times higher odds (OR 3.16;
      95% CI: 1.12-8.95) of having halitosis. Meta-regression and subgroups analyses
      showed that criteria used for halitosis and periodontitis assessment explained
      nearly 45% and 24% of heterogeneity between studies, respectively. CONCLUSIONS:
      Positive association between periodontitis and halitosis was found in pooled
      results of population-based observational studies. However, this evidence is
      derived from cross-sectional studies.

PMID- 28749583
TI  - Chiral Sulfur Functional Groups as Definers of the Chirality at the Metal in Ir
      and Rh Half-Sandwich Complexes: A Combined CD/X-ray Study.
AB  - Mesoionic carbenes (MICs) derived from triazolium salts that contain chiral
      sulfoxide or sulfoximine functional groups were used to construct enantiopure
      chiral-at-metal IrIII and RhIII half-sandwich complexes through the synthetic
      sequence of MIC complexation/C-H aromatic activation. The process was efficient
      and diastereoselective for the formation of enantiopure five-membered
      metallacycles. The use of the enantiomers of the chiral sulfur groups allowed us
      to prepare complexes that had opposite configurations at the metal center.
      Complete retention of the configuration at the metal center was observed during
      the formation of cationic IrIII complexes and upon insertion of alkynes into the
      IrIII -C bond, as demonstrated by a combined circular dichroism/X-ray study.
      These results point to a vicinal-assisted SN 1-like mechanism.

PMID- 28749584
TI  - The ALDH21 gene found in lower plants and some vascular plants codes for a NADP+ 
      dependent succinic semialdehyde dehydrogenase.
AB  - Lower plant species including some green algae, non-vascular plants (bryophytes)
      as well as the oldest vascular plants (lycopods) and ferns (monilophytes) possess
      a unique aldehyde dehydrogenase (ALDH) gene named ALDH21, which is upregulated
      during dehydration. However, the gene is absent in flowering plants. Here, we
      show that ALDH21 from the moss Physcomitrella patens codes for a tetrameric NADP+
      -dependent succinic semialdehyde dehydrogenase (SSALDH), which converts succinic
      semialdehyde, an intermediate of the gamma-aminobutyric acid (GABA) shunt
      pathway, into succinate in the cytosol. NAD+ is a very poor coenzyme for ALDH21
      unlike for mitochondrial SSALDHs (ALDH5), which are the closest related ALDH
      members. Structural comparison between the apoform and the coenzyme complex
      reveal that NADP+ binding induces a conformational change of the loop carrying
      Arg-228, which seals the NADP+ in the coenzyme cavity via its 2'-phosphate and
      alpha-phosphate groups. The crystal structure with the bound product succinate
      shows that its carboxylate group establishes salt bridges with both Arg-121 and
      Arg-457, and a hydrogen bond with Tyr-296. While both arginine residues are pre
      formed for substrate/product binding, Tyr-296 moves by more than 1 A. Both R121A
      and R457A variants are almost inactive, demonstrating a key role of each arginine
      in catalysis. Our study implies that bryophytes but presumably also some green
      algae, lycopods and ferns, which carry both ALDH21 and ALDH5 genes, can oxidize
      SSAL to succinate in both cytosol and mitochondria, indicating a more diverse
      GABA shunt pathway compared with higher plants carrying only the mitochondrial
      ALDH5.

PMID- 28749585
TI  - miR3954 is a trigger of phasiRNAs that affects flowering time in citrus.
AB  - In plant, a few 22-nt miRNAs direct cleavages of their targets and trigger the
      biogenesis of phased small interfering RNAs (phasiRNAs) in plant. In this study,
      we characterized a miRNA triggering phasiRNAs generation, miR3954, and explored
      its downstream target genes and potential function. Our results demonstrated that
      miR3954 showed specific expression in the flowers of citrus species, and it
      targeted a NAC transcription factor (Cs7 g22460) and two non-coding RNA
      transcripts (lncRNAs, Cs1 g09600 and Cs1 g09635). The production of phasiRNAs was
      detected from transcripts targeted by miR3954, and was further verified in both
      sequencing data and transient expression experiments. PhasiRNAs derived from the
      two lncRNAs targeted not only miR3954-targeted NAC gene but also additional NAC
      homologous genes. No homologous genes of these two lncRNAs were found in plants
      other than citrus species, implying that this miR3954-lncRNAs-phasiRNAs-NAC
      pathway is likely citrus-specific. Transgenic analysis indicated that the miR3954
      overexpressing lines showed decreased transcripts of lncRNA, elevated abundance
      of phasiRNAs and reduced expression of NAC genes. Interestingly, the
      overexpression of miR3954 leads to early flowering in citrus plants. In summary,
      our results illustrated a model of the regulatory network of miR3954-lncRNA
      phasiRNAs-NAC, which may be functionally involved in flowering in citrus.

PMID- 28749586
TI  - Patient Decisions to Receive Secondary Pharmacogenomic Findings and Development
      of a Multidisciplinary Practice Model to Integrate Results Into Patient Care.
AB  - Whole exome sequencing (WES) has the potential of identifying secondary findings
      that are predictive of poor pharmacotherapy outcomes. The purpose of this study
      was to investigate patients' wishes regarding the reporting of secondary
      pharmacogenomic findings. WES results (n = 106 patients) were retrospectively
      reviewed to determine the number of patients electing to receive secondary
      pharmacogenomic results. Phenotypes were assigned based on Clinical
      Pharmacogenetics Implementation Consortium (CPIC) guidelines. The percent of
      patients with a predicted phenotype associated with a gene-based CPIC dosing
      recommendation was determined. Ninety-nine patients (93.4%) elected to receive
      secondary pharmacogenomic findings. For each gene-drug pair analyzed, the number
      of patients with an actionable phenotype ranged from two (2%) to 43 patients
      (43.4%). Combining all gene-drug pairs, 84 unique patients (84.8%) had an
      actionable phenotype. A prospective multidisciplinary practice model was
      developed for integrating secondary pharmacogenomic findings into clinical
      practice. Our model highlights a unique collaboration between physician
      geneticists, pharmacists, and genetic counselors.

PMID- 28749587
TI  - Regional survey supports national initiative for 'water-only' schools in New
      Zealand.
AB  - OBJECTIVE: To support a national initiative to remove sugary drinks from schools
      and limit drinks to water or unflavoured milk ('water-only'). METHODS: We emailed
      all 201 schools with primary school aged children in the Greater Wellington
      region with a survey on (1) current status of, (2) support needs for, and (3)
      barriers to or lessons learned from, a 'water-only' school policy. RESULTS: Only
      78 (39%) of schools responded. Most supported 'water-only': 22 (28%) had
      implemented a policy; 10 (13%) in process of doing so; 22 (28%) were considering
      it; and 12 (15%) were 'water-only', but did not have a policy. Only 12 (15%) were
      not considering a 'water-only' policy. The main barrier reported was lack of
      community and/or family support. Many schools did not see any barriers beyond the
      time needed for consultation. Monitoring and communication were identified as key
      to success. A quarter of schools requested public health nurse support for a
      'water-only' policy. CONCLUSIONS: The survey elicited a range of views on 'water
      only' policies for schools, but suggests that 'water-only' may be an emerging
      norm for schools. Implications for public health: Our survey shows how local
      assessment can support a national initiative by providing a baseline, identifying
      schools that want support, and sharing lessons. Making schools 'water-only' could
      be a first step in changing our children's environment to prevent obesity.

PMID- 28749588
TI  - Primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell
      lymphoproliferative disorder: Report of a case and review of the literature.
AB  - Primary cutaneous small/medium-sized T-cell lymphoma (PCSM-TCL), which was
      included in the World Health Organization - European Organization for Research
      and Treatment of Cancer (WHO-EORTC) classification for cutaneous lymphomas as a
      provisional entity in 2008, has recently been reclassified as primary cutaneous
      small/medium-sized T-cell lymphoproliferative disorder (PCSM-TCLPD) because of
      its indolent behavior and uncertain malignant potential. Treatment with local
      therapies is usually curative, although there have been reports of aggressive,
      systemic disease. This spectrum of disease behavior evokes the consideration that
      this entity may actually be multiple diseases with a shared clinicopathologic
      features rather than a singular disease process with a variety of behaviors. PCSM
      TCLPD retained its designation as a provisional entity under the updated WHO
      EORTC guidelines; however, additional cases of PCSM-TCLPD are needed to shed more
      light on this rare disorder.

PMID- 28749589
TI  - Precisely Assembled Cyclic Gold Nanoparticle Frames by 2D Polymer Single-Crystal
      Templating.
AB  - In recent decades, extensive studies have been devoted to assembling
      nanoparticles (NPs) into various ordered structures to achieve novel optical
      properties. However, it still remains a challenging task to assemble NPs into
      cyclic one-dimensional (1D) shapes, such as rings and frames. Herein, we report a
      directed assembly method to precisely assemble NPs into well-defined, free
      standing frames using polymer single crystals (PSCs) as the template. Preformed
      poly(ethylene oxide) (PEO) single crystals were used as the template to direct
      the crystallization of block copolymer (BCP) poly(ethylene oxide)-b-poly(4
      vinylpyridine) (PEO-b-P4VP), which directs the gold NPs (AuNPs) to form AuNP
      frames. By controlling the PSC growth, we were able to, for the first time,
      precisely tune both the size and width of the AuNP frame. These novel AuNP frames
      topologically resemble NP nanorings and cyclic polymer chains, and show unique
      surface plasmon resonance (SPR) behaviors.

PMID- 28749590
TI  - The Marulu Strategy 2008-2012: overcoming Fetal Alcohol Spectrum Disorder (FASD)
      in the Fitzroy Valley.
AB  - OBJECTIVE: Aboriginal leaders concerned about high rates of Fetal Alcohol
      Spectrum Disorder (FASD) in the Fitzroy Valley, remote north-western Australia,
      introduced restrictions on access to take-away full-strength alcohol. Following
      this, Aboriginal leaders engaged strategic partners in a broader strategy to
      address FASD in the region. The aim of this study was to develop and implement a
      community-led, researcher-supported, FASD strategy. METHODS: A review of
      literature focusing on community-led FASD strategies identified key components
      that informed the Marulu FASD strategy. These included strategy ownership,
      leadership, and governance by participating communities, and a research
      framework. RESULTS: Community meetings and workshops led to the development of
      The Marulu FASD Strategy (2008). Feasibility and community consent to conduct a
      FASD prevalence study (the Lililwan Project) was confirmed, and implementation
      was progressed (2010-2013). Concurrent FASD prevention activities were conducted.
      In 2012, the Marulu FASD Unit was established within a local Aboriginal
      organisation to sustain and coordinate ongoing strategy activities. CONCLUSIONS:
      Community control of public health initiatives can be achieved when Aboriginal
      communities prioritise issues of significant concern, and engage strategic
      partners to overcome them. Implications for public health: The Marulu Strategy
      forms a template for action to address FASD and other public health issues in
      Aboriginal communities in Australia and internationally.

PMID- 28749591
TI  - Free smoking cessation mobile apps available in Australia: a quality review and
      content analysis.
AB  - OBJECTIVES: This review aimed to identify free, high-quality, smoking cessation
      mobile applications (apps) that adhere to Australian smoking cessation treatment
      guidelines. METHODS: A systematic search of smoking cessation apps was conducted
      using Google. The technical quality of relevant apps was rated using the Mobile
      Application Rating Scale. The content of apps identified as high quality was
      assessed for adherence to smoking cessation treatment guidelines. RESULTS: 112
      relevant apps were identified. The majority were of poor technical quality and
      only six 'high-quality' apps were identified. These apps adhered to Australian
      treatment guidelines in part. The efficacy of two apps had been previously
      evaluated. CONCLUSIONS: In lieu of more substantial research in this area, it is
      suggested that the high-quality apps identified in this review may be more likely
      than other available apps to encourage smoking cessation. Implications for public
      health: Smoking cessation apps have the potential to address many barriers that
      prevent smoking cessation support being provided; however few high-quality
      smoking cessation apps are currently available in Australia, very few have been
      evaluated and the app market is extremely volatile. More research to evaluate
      smoking cessation apps, and sustained funding for evidence-based apps, is needed.

PMID- 28749592
TI  - Porphyrin Antennas on Carbon Nanodots: Excited State Energy and Electron
      Transduction.
AB  - We report the synthesis and electron donor-acceptor features of a novel
      nanohybrid, in which the light-harvesting and electron-donating properties of a
      meso-tetraarylporphyrin (TArP) are combined with the electron-accepting features
      of nitrogen-doped carbon nanodots (NCNDs). In particular, in an ultrafast process
      (>1012  s-1 ), visible-light excitation transforms the strongly quenched
      porphyrin singlet excited states into short-lived (225 ps) charge-separated
      states. On the other hand, ultraviolet light excitation triggers a non-resolvable
      transduction of singlet excited state energy from the NCNDs to the porphyrins,
      followed by the same charge separation observed upon visible light excitation.

PMID- 28749593
TI  - Developing better practices at the institutional level leads to better outcomes
      after pancreaticoduodenectomy in 3,378 patients: domestic audit of the Japanese
      Society of Pancreatic Surgery.
AB  - BACKGROUND: The aim of the present study was to assess recent trends in
      pancreaticoduodenectomy (PD) and the role of institutional standardization on the
      development of postoperative complications in 3,378 patients who underwent PD in
      Japan. METHODS: Data were collected from 3,378 patients who underwent PD in 2006,
      2010 and 2014 at 53 institutions. A standardized institution (SI) was defined as
      one that implements >=7 of 13 quality initiatives according to departmental
      policy. There were 1,223 patients in the SI group and 2,155 in the non-SI group.
      Clinical parameters were compared over time, and between groups. Risk factors for
      morbidity and mortality were assessed by logistic regression analysis with a
      mixed-effects model. RESULTS: The number of patients who underwent PD in SIs
      increased from 16.5% in 2006 to 46.4% in 2014. The SI group experienced an
      improved process of care and a lower frequency of severe complications vs. the
      non-SI group (P < 0.001). Multivariate analysis revealed that the SI group was
      associated with a lower incidence of delayed gastric emptying (odds ratio -0.499,
      P = 0.008) and incisional surgical site infection (odds ratio -0.999, P < 0.001).
      CONCLUSION: Standardization of care in PD may be important in reducing post-PD
      complications, and is a critical element for improving clinical outcomes.

PMID- 28749594
TI  - Seizure activity per se does not induce tissue damage markers in human
      neocortical focal epilepsy.
AB  - OBJECTIVE: The contribution of recurring seizures to the progression of
      epileptogenesis is debated. Seizure-induced brain damage is not conclusively
      demonstrated either in humans or in animal models of epilepsy. We evaluated the
      expression of brain injury biomarkers on postsurgical brain tissue obtained from
      20 patients with frequent seizures and a long history of drug-resistant focal
      epilepsy. METHODS: The expression patterns of specific glial, neuronal, and
      inflammatory molecules were evaluated by immunohistochemistry in the core of type
      II focal cortical dysplasias (FCD-II), at the FCD boundary (perilesion), and in
      the adjacent normal-appearing area included in the epileptogenic region. We also
      analyzed surgical specimens from cryptogenic patients not presenting structural
      alterations at imaging. RESULTS: Astroglial and microglial activation, reduced
      neuronal density, perivascular CD3-positive T-lymphocyte clustering, and
      fibrinogen extravasation were demonstrated in the core of FCD-II lesions. No
      pathological immunoreactivity was observed outside the FCD-II or in cryptogenetic
      specimens, where the occurrence of interictal and ictal epileptiform activity was
      confirmed by either stereo-electroencephalography or intraoperative
      electrocorticography. INTERPRETATION: Recurrent seizures do not induce the
      expression of brain damage markers in nonlesional epileptogenic cortex studied in
      postsurgical tissue from cryptogenic and FCD patients. This evidence argues
      against the hypothesis that epileptiform activity per se contributes to focal
      brain injury, at least in the neocortical epilepsies considered here. Ann Neurol
      2017;82:331-341.

PMID- 28749595
TI  - Morbidity and mortality in infant mountain gorillas (Gorilla beringei beringei):
      A 46-year retrospective review.
AB  - Long-term studies of morbidity and mortality in free-ranging primates are scarce,
      but may have important implications for the conservation of extant populations.
      Infants comprise a particularly important age group, as variation in survival
      rates may have a strong influence on population dynamics. Since 1968, the
      Mountain Gorilla Veterinary Project (MGVP, Inc.) and government partners have
      conducted a comprehensive health monitoring and disease investigation program on
      mountain gorillas (Gorilla beringei beringei) in Rwanda, Uganda, and the
      Democratic Republic of the Congo. In an effort to better understand diseases in
      this species, we reviewed reliable field reports (n = 37), gross post-mortem (n =
      66), and histopathology (n = 53) reports for 103 infants (less than 3.5 years)
      mountain gorillas in the Virunga Massif. Our aim was to conduct the first
      comprehensive analysis of causes of infant mortality and to correlate
      histological evidence with antemortem morbidity in infant mountain gorillas.
      Causes of morbidity and mortality were described, and compared by age, sex, and
      over time. Trauma was the most common cause of death in infants (56%), followed
      by respiratory infections and aspiration (13%). Gastrointestinal parasitism
      (33%), atypical lymphoid hyperplasia (suggestive of infectious disease) (31%),
      and hepatic capillariasis (25%) were the most significant causes of antemortem
      morbidity identified post-mortem. Identifying the causes of mortality and
      morbidity in infants of this critically endangered species will help to inform
      policy aimed at their protection and guide ante- and post-mortem health
      monitoring and clinical decision-making in the future.

PMID- 28749596
TI  - Climate Change, Climate Justice, and Environmental Health: Implications for the
      Nursing Profession.
AB  - PURPOSE: Climate change is an emerging challenge linked to negative outcomes for
      the environment and human health. Since the 1960s, there has been a growing
      recognition of the need to address climate change and the impact of greenhouse
      gas emissions implicated in the warming of our planet. There are also deleterious
      health outcomes linked to complex climate changes that are emerging in the 21st
      century. This article addresses the social justice issues associated with climate
      change and human health and discussion of climate justice. ORGANIZING CONSTRUCT:
      Discussion paper. METHODS: A literature search of electronic databases was
      conducted for articles, texts, and documents related to climate change, climate
      justice, and human health. FINDINGS: The literature suggests that those who
      contribute least to global warming are those who will disproportionately be
      affected by the negative health outcomes of climate change. The concept of
      climate justice and the role of the Mary Robinson Foundation-Climate Justice are
      discussed within a framework of nursing's professional responsibility and the
      importance of social justice for the world's people. The nursing profession must
      take a leadership role in engaging in policy and advocacy discussions in
      addressing the looming problems associated with climate change. CONCLUSIONS:
      Nursing organizations have adopted resolutions and engaged in leadership roles to
      address climate change at the local, regional, national, and global level. It is
      essential that nurses embrace concepts related to social justice and engage in
      the policy debate regarding the deleterious effects on human health related to
      global warming and climate change. Nursing's commitment to social justice offers
      an opportunity to offer significant global leadership in addressing the health
      implications related to climate change. CLINICAL RELEVANCE: Recognizing the
      negative impacts of climate change on well-being and the underlying socioeconomic
      reasons for their disproportionate and inequitable distribution can expand and
      optimize the profession's role in education, practice, research, and policy
      making efforts to address climate change.

PMID- 28749597
TI  - A Structural Model of Nitro-Porphyrin Dyes Based on Spectroscopy and Density
      Functional Theory.
AB  - Nitro-porphyrins are an important class of commercial dyes with a range of
      potential applications. The nitro group is known to dramatically affect the
      photophysics of the porphyrin, but there are few systematic investigations of the
      contributing factors. To address this deficiency, we present spectroscopic
      studies of a series of nitro-porphyrins, accompanied by density functional theory
      calculations to elucidate their structures. In particular, we explore how the
      positions of the substituents affect the energy levels and nuclear geometry. As
      expected, nitro groups on the meso-phenyl rings cause small changes to the
      orbital energies by induction, while those at the beta-pyrrole positions more
      strongly conjugate into the aromatic system. In addition, however, we find
      evidence that beta-pyrrole nitro groups distort the porphyrin, creating two non
      planar conformations with distinct properties. This unexpected result helps
      explain the anomalous photophysics of nitro-porphyrins reported throughout the
      literature, including inhomogeneous line broadening and biexponential
      fluorescence decay. (c) 2017 Wiley Periodicals, Inc.

PMID- 28749598
TI  - Beyond Farnesoid X receptor to target new therapies for NAFLD.

PMID- 28749599
TI  - Heat-induced inflammation and its role in esophageal cancer.
AB  - Esophageal cancer, the sixth most common cause of death from cancer worldwide,
      consists of different histological types and displays various patterns of
      incidence. Esophageal adenocarcinoma and esophageal squamous cell carcinoma are
      the most prevalent types. As epidemiological studies report that ingesting hot
      substances is one major risk factor for squamous cell carcinoma, evaluating the
      effect of this external stress on esophagus cells seems desirable. This specific
      kind of stress brings about cellular changes and stabilizes them by affecting
      different cellular features such as genetic stability, membrane integrity and the
      regulation of signaling pathways. It also causes tissue injury by affecting the
      extracellular matrix and cell viability. Thus, one of the main consequences of
      thermal injury is the activation of the immune system, which can result in
      chronic inflammation. The genetic alteration that has occurred during thermal
      injury and the consequent reduction in the function of repair systems is further
      strengthened by chronic inflammation, thereby increasing the probability that
      mutated cell lines may appear. The molecules that present in this circumstance,
      such as heat shock proteins, cytokines, chemokines and other inflammatory
      factors, affect intercellular signaling pathways, including nuclear factor kappa
      light-chain-enhancer of activated B cells, signal transducer activator of
      transcription-3 and hypoxia-inducible factor 1alpha in supporting the survival
      and emergence of mutant phenotypes and the consequent malignant progression in
      altered cell lines. This investigation of these effective factors and their
      probable role in the tumorigenic path may improve current understanding.

PMID- 28749600
TI  - PyRETIS: A well-done, medium-sized python library for rare events.
AB  - Transition path sampling techniques are becoming common approaches in the study
      of rare events at the molecular scale. More efficient methods, such as transition
      interface sampling (TIS) and replica exchange transition interface sampling
      (RETIS), allow the investigation of rare events, for example, chemical reactions
      and structural/morphological transitions, in a reasonable computational time.
      Here, we present PyRETIS, a Python library for performing TIS and RETIS
      simulations. PyRETIS directs molecular dynamics (MD) simulations in order to
      sample rare events with unbiased dynamics. PyRETIS is designed to be easily
      interfaced with any molecular simulation package and in the present release, it
      has been interfaced with GROMACS and CP2K, for classical and ab initio MD
      simulations, respectively. (c) 2017 Wiley Periodicals, Inc.

PMID- 28749601
TI  - A Chiral Recognition System Orchestrated by Self-Assembly: Molecular Chirality,
      Self-Assembly Morphology, and Fluorescence Response.
AB  - The newly developed oligophenylenevinylene (OPV)-based fluorescent (FL) chiral
      chemosensor (OPV-Me) for the representative enantiomeric guest, 1,2
      cyclohexanedicarboxylic acid (1,2-CHDA: RR- and SS-form) showed the high chiral
      discrimination ability, resulting in the different aggregation modes of OPV-Me
      self-assembly: RR-CHDA directed the fibrous supramolecular aggregate, whereas SS
      CHDA directed the finite aggregate. The consequent FL intensity toward RR-CHDA
      was up to 30 times larger than that toward SS-CHDA. Accordingly, highly
      enantioselective recognition was achieved. Application to the chirality sensing
      was also possible: OPV-Me exhibited a linear relationship between the FL
      intensity and the enantiomeric excess through the morphological development of
      stereocomplex aggregates. These results clearly show that the chiral recognition
      ability is manifested by the amplification cascade of the chirality difference
      through self-assembly.

PMID- 28749603
TI  - Protection motivation theory in predicting intention to receive cervical cancer
      screening in rural Chinese women.
AB  - OBJECTIVE: Despite the significance of cervical cancer screening, motivating more
      women to participate remains a challenge in resource-limited settings. In this
      study, we tested the protection motivation theory (PMT) in predicting screening
      intentions. METHODS: Participants were women from Wufeng, a typical rural county
      in China. Participants (n = 3000) with no cervical cancer history were recruited
      from 10 randomly selected villages. As mediating variables, 6 PMT constructs
      (Perceived Risk, Fear Arousal, Perceived Severity, Response Efficacy, Response
      Cost, and Self-Efficacy) were measured using the standardized questionnaire.
      Structural equation modeling (SEM) method was employed to test PMT-based
      prediction models. RESULTS: Of the total sample, 57.77% believed that regular
      screening may reduce cervical cancer risk, and 45.26% agreed that women should be
      screened regularly. Our data fit the PMT model well (GFI = 0.95, AGFI = 0.93, CFI
      = 0.90, RMSEA = 0.06, SRMR = 0.04, Chi-square/df = 2.47). Knowledge of screening
      was directly and positively associated with screening intention. Age, annual
      income, and awareness of and prior experience with screening were significantly
      associated with screening intention by enhancing cervical cancer risk perception
      and by reducing response cost (P<0.05 for both). CONCLUSION: PMT can be used as
      guidance to investigate cervical cancer screening intentions among rural women in
      China with focus on cancer knowledge, some demographic factors, and awareness of
      and previous experience with screening. These findings, if verified with
      longitudinal data, can be used for intervention program development.

PMID- 28749602
TI  - Clinical pattern and prevalence of upper gastrointestinal toxicity in patients
      abusing ketamine.
AB  - OBJECTIVE: Evaluations of upper gastrointestinal toxicity from ketamine abuse are
      uncommon. This study investigated the clinical pattern of upper gastrointestinal
      symptoms in patients inhaling ketamine. METHODS: In a cross-sectional study of
      611 consecutive patients who were seeking treatment for ketamine uropathy in a
      tertiary hospital setting between August 2008 and June 2016, their clinical
      pattern of upper gastrointestinal symptoms was evaluated and compared with a
      control population of 804 non-users. RESULTS: A total of 168 (27.5%) patients
      abusing ketamine (mean age 26.3 years, 58.9% female) reported the presence of
      upper gastrointestinal symptoms. These symptoms were significantly more prevalent
      in patients inhaling ketamine than in those who were not (27.5% vs 5.2%, P <
      0.001). Their mean duration of ketamine abuse before symptom presentation was 5.0
      +/- 3.1 years. The presenting symptoms included epigastric pain (n = 155, 25.4%),
      recurrent vomiting (n = 48, 7.9%), anemia (n = 36, 5.9%) and gastrointestinal
      bleeding (n = 20, 3.3%). Uropathy symptoms were preceded by upper
      gastrointestinal symptoms for 4.4 +/- 3.0 years in 141 (83.9%) patients. Logistic
      regression showed that elder age (odds ratio [OR] 1.06, P = 0.04), active abuser
      status (OR 1.60, P = 0.04) and longer duration of ketamine abuse (OR 1.00, P =
      0.04) were independent factors associated with upper gastrointestinal toxicity.
      CONCLUSIONS: Although epigastric symptoms are unusual in the young population,
      upper gastrointestinal toxicity was highly prevalent in those inhaling ketamine.
      Enquiries about ketamine abuse are recommended when assessing young patients with
      epigastric symptoms.

PMID- 28749604
TI  - A simulation of dementia epidemiology and resource use in Australia.
AB  - OBJECTIVES: The number of people in the developed world who have dementia is
      predicted to rise markedly. This study presents a validated predictive model to
      assist decision-makers to determine this population's future resource
      requirements and target scarce health and welfare resources appropriately.
      METHODS: A novel individual patient discrete event simulation was developed to
      estimate the future prevalence of dementia and related health and welfare
      resource use in Australia. RESULTS: When compared to other published results, the
      simulation generated valid estimates of dementia prevalence and resource use. The
      analysis predicted 298,000, 387,000 and 928,000 persons in Australia will have
      dementia in 2011, 2020 and 2050, respectively. Health and welfare resource use
      increased markedly over the simulated time-horizon and was affected by capacity
      constraints. CONCLUSIONS: This simulation provides useful estimates of future
      demands on dementia-related services allowing the exploration of the effects of
      capacity constraints. Implications for public health: The model demonstrates that
      under-resourcing of residential aged care may lead to inappropriate and
      inefficient use of hospital resources. To avoid these capacity constraints it is
      predicted that the number of aged care beds for persons with dementia will need
      to increase more than threefold from 2011 to 2050.

PMID- 28749605
TI  - Housing tenure as a focus for reducing inequalities in the home safety
      environment: evidence from Growing Up in New Zealand.
AB  - OBJECTIVES: To determine whether specific demographic characteristics are
      associated with the presence or absence of household safety strategies. METHODS:
      This study was conducted within Growing Up in New Zealand, a contemporary
      longitudinal study of New Zealand (NZ) children. Multivariable analyses were used
      to examine the maternal (self-prioritised ethnicity, education, age, self
      reported health) and household (area-level deprivation, tenure, crowding,
      residential mobility, dwelling type) determinants of household safety strategies
      being present in the homes of young children. RESULTS: In comparison to family
      owned homes, privately owned rental homes were less likely (OR=0.78; 95%CI 0.65
      0.92), and government-owned rental homes were more likely (OR=1.74, 95%CI 1.25
      2.41) to have eight or more household safety strategies present. CONCLUSIONS:
      Living in a privately owned rental home in NZ exposes children to an environment
      where there are fewer household safety strategies in place. Implications for
      public health: Housing tenure provides a clear target focus for improving the
      household safety environment for NZ children.

PMID- 28749606
TI  - Perceived stress is associated with increased rostral middle frontal gyrus
      cortical thickness: a family-based and discordant-sibling investigation.
AB  - Elevated stress perception and depression commonly co-occur, suggesting that they
      share a common neurobiology. Cortical thickness of the rostral middle frontal
      gyrus (RMFG), a region critical for executive function, has been associated with
      depression- and stress-related phenotypes. Here, we examined whether RMFG
      cortical thickness is associated with these phenotypes in a large family-based
      community sample. RMFG cortical thickness was estimated using FreeSurfer among
      participants (n = 879) who completed the ongoing Human Connectome Project.
      Depression-related phenotypes (i.e. sadness, positive affect) and perceived
      stress were assessed via self-report. After accounting for sex, age, ethnicity,
      average whole-brain cortical thickness, twin status and familial structure, RMFG
      thickness was positively associated with perceived stress and sadness and
      negatively associated with positive affect at small effect sizes (accounting for
      0.2-2.4% of variance; p-fdr: 0.0051-0.1900). Perceived stress was uniquely
      associated with RMFG thickness after accounting for depression-related
      phenotypes. Further, among siblings discordant for perceived stress, those
      reporting higher perceived stress had increased RMFG thickness (P = 4 * 10-7 ).
      Lastly, RMFG thickness, perceived stress, depressive symptoms, and positive
      affect were all significantly heritable, with evidence of shared genetic and
      environmental contributions between self-report measures. Stress perception and
      depression share common genetic, environmental, and neural correlates.
      Variability in RMFG cortical thickness may play a role in stress-related
      depression, although effects may be small in magnitude. Prospective studies are
      required to examine whether variability in RMFG thickness may function as a risk
      factor for stress exposure and/or perception, and/or arises as a consequence of
      these phenotypes.

PMID- 28749607
TI  - "Assessment of relationship between xerostomia and oral health-related quality of
      life in patients with rheumatoid arthritis".
AB  - OBJECTIVE: To determine the relationship between xerostomia and oral health
      related quality of life in patients with rheumatoid arthritis. MATERIALS AND
      METHOD: Two hundred patients with rheumatoid arthritis were assessed using Fox
      and OHIP-14 questionnaires concerning xerostomia and oral health-related quality
      of life, respectively. The sum of decayed, missing, and filled teeth (DMFT) was
      determined via an intra-oral examination. In addition, intergroup comparisons
      were evaluated using t test, chi-square, regression, and Tukey analysis. RESULT:
      Among rheumatoid arthritis patients, 51% had been afflicted with xerostomia. We
      found a statistically significant relationship between xerostomia and oral health
      related quality of life (p-value=.004), as xerostomia cases have significantly
      worse oral health-related quality of life. Also, there was a statistically
      significant association between oral health-related quality of life and gender as
      well as DMFT. CONCLUSION: Because there seem to be a high prevalence of
      xerostomia in patients with rheumatoid arthritis, screening in such population is
      highly recommended. Therefore, educational programs and/or workshops should be
      encouraged among healthcare providers to prevent worsening of oral health-related
      quality of life.

PMID- 28749608
TI  - Prone position ventilation support for acute exacerbation of interstitial lung
      disease?
AB  - INTRODUCTION: Prone position ventilation (PPV) has been shown to improve
      oxygenation and decrease pulmonary vascular resistance and mortality in patients
      with severe acute respiratory distress syndrome (ARDS). Whether these benefits of
      PPV occur similarly in acute exacerbations of interstitial lung disease (ILD) is
      not clear. We retrospectively explored the use of PPV in acute exacerbation with
      ILD versus those with severe acute respiratory distress syndrome (severe ARDS).
      METHODS: Retrospective study of the application of PPV in 17 patients with acute
      exacerbations of ILD and in 19 patients with severe ARDS. Pre- and post-PPV
      hemodynamic parameters, respiratory mechanics, prognostic indicators,
      complications and mortality rates at 28, 60 and 90 days were compared. RESULTS:
      There was no difference in baseline characteristics between the two groups except
      for higher driving pressure and more diastolic dysfunction in ILD group than
      severe ARDS group Compared with pre-PPV, cardiac index and driving pressure
      remained unchanged post-PPV in both groups. PPV increased PaO2 /FiO2 [118.7
      (92.0, 147.8) pre-PPV vs 132.0 (93.5, 172.0) post-PPV; P < 0.05] and central
      venous oxygenation in patients with ILD. In patients with severe ARDS, PPV
      significantly increased PaO2 /FiO2 [109.23 (89,135) pre- PPV vs 126.13 (100.93,
      170) post-PPV; P < 0.05] and intrathorax blood volume index. However, mortality
      rates at 28, 60 and 90 days remained high in both groups (76.4%, 88.2% and 88.2%
      vs 36.8%, 57.9% and 57.9% in ILD and severe ARDS, respectively; P < 0.05).
      CONCLUSION: Our findings suggest that PPV may improve oxygenation and partially
      improve hemodynamic parameters during acute exacerbations of ILD.

PMID- 28749609
TI  - Ricochet pollination in Senna (Fabaceae) - petals deflect pollen jets and promote
      division of labour among flower structures.
AB  - Naturalists Fritz and Hermann Muller hypothesised that heteranthery often leads
      to a division of labour into 'feeding' and 'pollinating' stamens; the latter
      often being as long as the pistil so as to promote successful pollination on the
      bees' back. In many buzz-pollinated species of Senna, however, the so-called
      pollinating stamens are short and not level with the stigma, raising the question
      of how pollen is shed on the bees' back. Here we explore a mechanism called
      'ricochet pollination'. We test whether division of labour is achieved through
      the interaction between short lower stamens and strongly concave 'deflector
      petals'. We studied the arrangement and morphology of the floral organs involved
      in the ricochet pollination, functioning of the flowers through artificial
      sonication and observed the interactions between bees and flowers in the field.
      The middle stamens are adapted to eject pollen downwards, which can be readily
      collected on the bee mid legs. Most of the pollen is ejected towards the
      deflector petal(s). Pollen from this set of stamens is more likely to contribute
      to pollination. The pollen grains seem to ricochet multiple times against the
      deflector petals to eventually reach the bee's back. The pollen ricochet
      mechanism promotes a division of labour by involving additional floral organs,
      such as petals, reinforcing the Mullers' division-of-labour hypothesis. However,
      alternative, non-multiexclusive hypotheses could be explored in genus Senna and
      other angiosperm species.

PMID- 28749612
TI  - Corrigendum.

PMID- 28749611
TI  - Morphology, Ultrastructure, and Molecular Phylogeny of Rozella multimorpha, a New
      Species in Cryptomycota.
AB  - Increasing numbers of sequences of basal fungi from environmental DNA studies are
      being deposited in public databases. Many of these sequences remain unclassified
      below the phylum level because sequence information from identified species is
      sparse. Lack of basic biological knowledge due to a dearth of identified species
      is extreme in Cryptomycota, a new phylum widespread in the environment and
      phylogenetically basal within the fungal lineage. Consequently, we are attempting
      to fill gaps in the knowledge of Rozella, the best-known genus in this lineage.
      Rozella is a genus of unwalled, holocarpic, endobiotic parasites of hosts
      including Chytridiomycota, Blastocladiomycota, Oomycota, Basidiomycota, and a
      green alga, with most species descriptions based on morphology and host
      specificity. We found a Rozella parasitizing a Pythium host that was a saprobe on
      spruce pollen bait placed with an aquatic sample. We characterized the parasite
      with light microscopy, TEM of its zoospores and sporangia, and its 18S/28S rDNA.
      Comparison with other Rozella species indicates that the new isolate differs
      morphologically, ultrastructurally, and genetically from Rozella species for
      which we have data. Features of the zoospore also differ from those of previously
      studied species. Herein we describe the Rozella as a new species, R. multimorpha.

PMID- 28749613
TI  - Linked selection, demography and the evolution of correlated genomic landscapes
      in birds and beyond.
AB  - Selection has a deep impact on the distribution of genetic diversity and
      population differentiation along the genome (the genomic landscapes of diversity
      and differentiation), reducing diversity and elevating differentiation not only
      at the sites it targets, but also at linked neutral sites. Fuelled by the high
      throughput sequencing revolution, these genomic footprints of selection have been
      extensively exploited over the past decade with the aim to identify genomic
      regions involved in adaptation and speciation. However, while this research has
      shown that the genomic landscapes of diversity and differentiation are usually
      highly heterogeneous, it has also led to the increasing realization that this
      heterogeneity may evolve under processes other than adaptation or speciation. In
      particular, instead of being an effect of selective sweeps or barriers to gene
      flow, accentuated differentiation can evolve by any process reducing genetic
      diversity locally within the genome (Charlesworth, ), including purifying
      selection at linked sites (background selection). In particular, in genomic
      regions where recombination is infrequent, accentuated differentiation can evolve
      as a by-product of diversity reductions unrelated to adaptation or speciation
      (Cruickshank & Hahn, ; Nachman & Payseur, ; Noor & Bennett, ). In such genomic
      regions, linkage extends over physically larger genome stretches, and selection
      affects a particularly high number of linked neutral sites. Even though the
      effects of selection on linked neutral diversity (linked selection) within
      populations are well documented (Cutter & Payseur, ), recent observations of
      diversity and differentiation landscapes that are highly correlated even among
      independent lineages suggest that the effects of long-term linked selection may
      have a deeper impact on the evolution of the genomic landscapes of diversity and
      differentiation than previously anticipated. The study on Saxicola stonechats by
      Van Doren et al. () reported in the current issue of Molecular Ecology lines in
      with a rapidly expanding body of evidence in this direction. Correlations of
      genomic landscapes extending from within stonechats to comparisons with Ficedula
      flycatchers add to recent insights into the timescales across which the effects
      of linked selection persist. Absent and inverted correlations of genomic
      landscapes in comparisons involving an island taxon, on the other hand, provide
      important empirical clues about the role of demographic constraints in the
      evolution of the genomic landscapes of diversity and differentiation.

PMID- 28749615
TI  - Corrigendum.

PMID- 28749614
TI  - Dissecting the dynamics of trans-generational immune priming.
AB  - The transfer of immunity from mother to offspring is a central way to endow the
      offspring with increased protection against pathogens. This phenomenon is not
      only found within the vertebrate domain: in some circumstances, invertebrate
      mothers can also give their offspring an immune kick-start, which is termed trans
      generational immune priming (TGIP). TGIP has been uncovered for a number of
      invertebrate species, but it is not ubiquitously evident. The reasons for which
      are not known. In this issue of Molecular Ecology, Tate, Andolfatto, Demuth, and
      Graham () probe the molecular underpinnings of TGIP in concert with the temporal
      dynamics of the response in the red flour beetle, Tribolium castaneum, infected
      with the bacterium Bacillus thuringiensis (Figure ). They provide previously
      lacking evidence for the repeatability of TGIP, meaning that when averaged across
      several experiments, the offspring of mothers infected with heat-killed bacteria
      had better survival when they themselves were infected with live bacteria than
      offspring from mothers that had not encountered the bacterium. In a detailed
      temporal examination of the offspring's acute infection phase (zero to 24 hr
      after infection), Tate et al. () follow T. castaneum's gene regulation responses
      to infection while simultaneously documenting bacterial load. Such an approach
      gives considerable insight into the physiological processes that occur in primed
      offspring, and a first glance at a potential role for tolerance and effects on
      host metabolism that might even resemble trained immunity, which is a form of
      innate immune memory in vertebrates.

PMID- 28749616
TI  - Joint Effects of Low Body Mass Index and Alcohol Consumption on Developing
      Esophageal Squamous Cell Cancer: a Korean Nationwide Population-Based Cohort
      Study
AB  - Objective: In Korea, 95% of esophageal cancer (EC) was the squamous cell-type. We
      sought to determine thecombined risk of alcohol consumption on developing
      esophageal squamous cell carcinoma (ESCC) in pre-diagnosticunderweight subjects
      using Korean national data. Methods: We analyzed the clinical data from a total
      of 264,084individuals aged 40 years or older, who received healthcare checkups
      arranged by the national insurance program,between 2003 and 2008 in Korea. Cox
      proportional hazards regression was used after adjusting confounding
      factors.Result: Newly diagnosed 278 EC was identified using the claims data
      during a median follow-up duration of 7.9 years.It was determined that
      underweight and obesity-compared with normal weight-were significantly associated
      with 73%increased risk and 30% decreased risk of EC, respectively. Weight gain
      reduced the risk of EC. Alcohol consumptionincreased risk for EC in a dose
      dependent manner. Heavy alcohol consumption in individuals with underweight
      increasedthe risk of developing EC dramatically. Conclusion: Underweight was a
      risk factor for ESCC and alcohol consumptionraised the risk synergistically with
      low BMI. Achieving normal range of BMI could reduce the risk of ESCC.

PMID- 28749617
TI  - Depression, Hopelessness and Social Support among Breast Cancer Patients: in
      Highly Endogamous Population
AB  - Aim: The aim of this study was to assess the relationship between different
      demographic variables, hopelessness,depression and social support of Breast
      cancer patients in Qatari's population. Design: This is an observational
      cohorthospital based study. Subjects and Methods: The study included 678 breast
      cancer patients. The questionnaires includeda demographic questionnaire, the Beck
      Hopelessness Scale (BHS), Back Depression Scale (BDS) and MultidimensionalScale
      of Perceived Social Support (MSPSS). The demographic questionnaire was used to
      assess patients' basicinformation including gender, age, marital status,
      education, family size, and place of residence. Medical informationregarding
      cancer stage, the time passed since diagnosis, treatment, and duration of disease
      were recorded. Results:The mean age of the studied women was 47.7+/-10.2 years.
      Among the studied patients, 34.7% were Qataris and 65.3%were Arab expatriates.
      Nearly 39.2% of the patients were in pre-menopausal status and 60.8% in post
      menopausalstatus. 86.1% of women were married. 14.6% were illiterate women, 20.9%
      were university graduates and 37.2%were housewives. Smoking habit was less common
      in studied Arab women (9.1%), but, sheesha smoking was morecommon, 17.7%. Daily
      physical activity indicated 25.7% were walking 30 minutes per-day and 14% were
      walking 60minutes per day. 30.4% of them had consanguineous parents. Breast
      feeding was practiced among 67.7% of women andover 73% were considered overweight
      and obese. Furthermore, over 75% of breast cancer women were at the Stage
      3(40.9%) and Stage 4 (35.8%) of cancer. The percentage of patients who underwent
      mastectomy and lumpectomy were49.3 % and 50.7%, respectively. It was observed
      that 27.7% of BDI patients had moderate depression and 19.5% ofthe BDI patients
      had severe depression and with mean and standard deviation 25.1+/-7.7. Also, the
      mean and SD of BDIfor consanguineous has showed statistically significant 28.4+/
      5.7 than non- consanguineous 23.2+/- 8.0 (p<0.001). Allsocio-demographic
      variables showed statistically significant differences with the total BHS score.
      The highest scorebelongs to the family sub-dimension. Conclusion: The present
      study indicates that hopelessness of the patients withbreast cancer decreased
      with the increase in their social support. Therefore, activating patient social
      support systems isof importance in increasing their levels of hope. The present
      study revealed the coexistence of the socio-demographic,physical, psychological,
      and cognitive problems faced by patients with cancer.

PMID- 28749618
TI  - Radiation-Induced Second Cancer Risk from External Beam Photon Radiotherapy for
      Head and Neck Cancer: Impact on in-Field and Out-of-Field Organs
AB  - The purpose of this paper is to provide data on development of second primary
      cancers within or adjacent to tissueirradiated in the treatment of primary head
      and neck cancers using different techniques and modalities. Materials andmethods:
      We selected five patients with HandN tumors located in base of the tongue for
      risk assessment. In order toexamine the impact of choices of various planning
      techniques, numbers of beams and beam energy used in treatmentplans - 7 and 9
      field Intensity modulated radiotherapy (IMRT) plans using 6MV and 10 MV beam
      energies and a 6MVVolumetric modulated arc therapy (VMAT) plans were planned. Out
      of-field measurements for secondary photondoses for the treatment plans were
      measured using diode-dosimeters and solid water slabs. Differential dose
      volumehistograms (DVH) for all 5 patients and 5 techniques, were exported and
      used to calculate organ equivalent dose (OAR),excess absolute risk (EAR), and
      life-time attributable risk (LAR) for in-field organs. Results: For all treatment
      plans,the DVH showed clinically acceptable values; adequate clinical target
      coverage and dose constraints were met for allorgans at risk. There was a clear
      advantage for the VMAT plan; it provided superior organ at risk (OAR) sparing
      andadequate target coverage. VMAT has relatively low monitor units at 0.93+/
      0.034 times 7F6. The average percentagescattered to prescription doses for the
      five patients at 15, 30, 45, 60 and 75 cm from the isocenter were 0.9212 +/-
      0.115,0.2621 +/- 0.080, 0.1617 +/- 0.057, 0.0936 +/- 0.026, 0.0296 +/- 0.014, for
      VMAT. Conclusion: Organ-specific LAR washigher with VMAT compared to 7F6 for
      skin. 6-MV VMAT is an acceptable alternative to IMRT for HandN cancerand offers
      advantages in terms of sparing adjacent OAR.

PMID- 28749619
TI  - Healthy Plant Foods Intake Could Protect Against Prostate Cancer Risk: A Case
      Control Study
AB  - Background: Several studies have investigated the association between healthy
      plant foods intake and prostatecancer risk with inconsistent results. So this
      study was conducted to examine the existence of any possible associationbetween
      healthy plant foods and prostate cancer risk. Materials and Methods: Sixty newly
      diagnosed prostate cancercases and 60 controls engaged in a hospital-based case
      control study. A validated 16o-items semi-quantitative FFQ wasused to assess
      usual dietary intakes. Energy-adjusted amounts of healthy plant foods intake were
      calculated using theresidual method. Logistic regression model was also used to
      derive beta estimates and odds ratios. Results: Cases wereolder and more likely
      to be inactive. In crude model, individuals in the highest tertile vs lowest
      tertile of total healthyplant foods (OR= 0.12; 95 % CI 0.04, 0.34), total fruits
      (OR= 0.11; 95 % CI 0.04, 0.30), total vegetables (OR= 0.08; 95% CI 0.03, 0.24),
      fresh fruits (OR= 0.11; 95 % CI 0.04, 0.30), and raw vegetables (OR= 0.06; 95 %
      CI 0.02, 0.18) hadsignificantly lower risk of prostate cancer. After controlling
      for potential confounders (age, BMI, total energy intake,job, education, smoking,
      physical activity, some drug usage, and also dietary intakes), just total healthy
      plant foods(OR= 0.12; 95 % CI 0.02, 0.55), total vegetables (OR=0.03; 95 % CI
      0.00, 0.25), and raw vegetables (OR= 0.01; 95% CI 0.00, 0.12) were associated
      with lower prostate cancer risk. Conclusions: The results of this study suggest
      thata diet rich in healthy plant foods and especially total or raw vegetable may
      protect against prostate cancer.

PMID- 28749620
TI  - Socioeconomic Inequality in Concurrent Tobacco and Alcohol Consumption
AB  - Background: Whilst several studies have examined inequity of tobacco use and
      inequity of alcohol drinkingindividually, comparatively little is known about
      concurrent tobacco and alcohol consumption. The present study
      thereforeinvestigated inequity of concurrent tobacco and alcohol consumption in
      Thailand. Methods: The 2015 Health andWelfare Survey was obtained from Thailand's
      National Statistical Office and used as a source of national representativedata.
      Concurrent tobacco and alcohol consumption was defined as current and concurrent
      use of both tobacco andalcohol. The wealth assets index was used as an indicator
      of socioeconomic inequity. Socioeconomic status included 5groups ranging from
      poorest (Q1) to richest (Q5). A total of 55,920 households and 113,705
      participants aged 15 yearsor over were included and analyzed. A weighted multiple
      logistic regression was performed. Results: The prevalenceof concurrent tobacco
      and alcohol consumption, tobacco consumption only, and alcohol consumption only
      were 15.2%(95% CI: 14.9, 15.4), 4.7% (95% CI: 4.5, 4.8), and 18.9% (95% CI: 18.7,
      19.1), respectively. Weighted multiplelogistic regression showed that concurrent
      tobacco and alcohol consumption was high in the poorest socioeconomicgroup (P for
      trend: <0.001), and tobacco consumption only was also high in the poorest group
      (P for trend: <0.001). Ahigh prevalence of alcohol consumption was observed in
      the richest group (P for trend: <0.001). Conclusions: Thesefindings suggest that
      tobacco and alcohol consumption prevention programs would be more effective if
      they consideredsocioeconomic inequities in concurrent tobacco and alcohol
      consumption rather than focusing on single drug use.

PMID- 28749621
TI  - Ten-Year Outcome of Different Treatment Modalities for Squamous Cell Carcinoma of
      Oral Cavity
AB  - Objective: This study reports outcomes of squamous cell carcinoma of oral cavity
      (SCCOC) patients with differenttreatment modalities. Materials and Methods: We
      evaluated the treatment outcomes of 775 newly diagnosed SCCOCpatients treated in
      our hospital between 2001 and 2010. Outcome data were obtained from the medical
      records. Survivalrates were estimated by the Kaplan-Meyer method. Cox
      proportional-hazard regression models were used to comparethe risk of death among
      all risk factors. Results: The patients were divided into group 1) surgery +/-
      adjuvant radiotherapy(RT) (n = 323) or group 2) RT +/- chemotherapy (CT) for
      curative intent (n = 315) or group 3) RT/CT for palliativeintent (n = 137). The
      overall 10-year survival rate was 17%. Statistically significant difference was
      noted in 10-yearoverall survival when SCCOC was managed surgically as compared to
      curative RT and palliative RT/CT with 25.3%, 12.9%, 4.7%, respectively. The
      hazard ratio of cancer death in group 1 was 2.0 (95% CI 1.7-2.4) as compared
      togroup 2. Conclusion: This study suggested that surgery must be the mainstay of
      treatment in locally advanced stageSCCOC. Palliative RT/CT still offered long
      term survival in some SCCOC patients.

PMID- 28749622
TI  - Understanding and Challenges in Taking Tyrosine Kinase Inhibitors among Malaysian
      Chronic Myeloid Leukemia Patients: A Qualitative Study
AB  - Background: In Malaysia, the treatment for chronic myeloid leukemia (CML) has
      long been delivered under theMalaysian Patient Assistance Program (MYPAP), but
      research on identifying factors contributing to non-adherence totyrosine kinase
      inhibitors (TKIs) is still limited. The current study explored understanding and
      challenges of MalaysianCML patients in taking imatinib and nilotinib. Methods:
      Semi-structured, face-to-face interviews were conductedwith 13 CML patients
      receiving treatment at a public tertiary care center, and were analyzed using the
      content analysisapproach. Results: The patients generally demonstrated inadequate
      knowledge, particularly of the natural history andstaging of CML, the function of
      TKIs, and the methods used for monitoring the effectiveness of treatment. A
      number ofthem also had experiences of withholding, skipping or altering the
      treatment, mainly due to the life-disturbing adversedrug effects (ADRs),
      forgetfulness, and religious and social issues. Besides, most of them were found
      having limitedskills in managing the ADRs, and not using prompts as reminders to
      take the medications. Furthermore, even thoughnilotinib was generally perceived
      as better tolerated as compared with imatinib, the inconvenience caused by the
      needto take it twice daily and on an empty stomach was constantly highlighted by
      the patients. Conclusion: While TKIsare widely used for CML treatment in
      Malaysia, the findings have revealed a lack of patient education and
      awareness,which warrants an integrated plan to reinforce medication adherence.

PMID- 28749623
TI  - Utility of Various Bronchoscopic Modalities in Lung Cancer Diagnosis
AB  - Background: Bronchoscopy and different techniques to obtain tissue sample form
      the cornerstone of lung cancerdiagnostics. The utility, specificity and
      sensitivity of various techniques are compared against each other and also
      inrelation to the tumour type, location and morphology. Aim: To assess and
      compare the utility of various bronchoscopicprocedures in lung malignancies.
      Study also compares the utility of these techniques on tumour site, morphology
      andcell type. Methods: One hundred and fifty six patients with suspected
      malignancies in whom bronchoscopy was deemedas the primary diagnostic procedure
      were selected. These patients underwent bronchoscopic lavage, brushings
      andbiopsy. Samples were assessed by microbiological, cytology and
      histopathological analysis. Results: Bronchoscopicprocedures have a high
      diagnostic accuracy of 81.25% in confirming lung malignancies in central tumours
      and alsoin non-accessible peripheral tumours. Bronchial brushings had the highest
      yield in central tumours (55.9%) and areasonably good yield even in perpipheral
      tumours (40.8%). When all the modalities were compared against each
      other,brushings was the single most decisive technique as it alone yielded a
      diagnosis in a significant 33% of cases, whereasthe comparative diagnosis by
      biopsy alone was in a minority 7.6% of cases.

PMID- 28749624
TI  - Synthesis, Characterization, and Evaluation of Cytotoxic Effects of Novel Hybrid
      Steroidal Heterocycles as PEG Based Nanoparticles
AB  - Anticancer agents featuring hybrid molecules can improve effectiveness and
      diminish drug resistance. The currentstudy aimed to introduce newly synthesized
      heterocyclic steroids of promising anticancer effects loaded in
      polyethyleneglycol (PEG)*based nanoparticles form. Several heterocyclic steroids
      (1-9) were synthesized via multicomponentreactions (MCRs) and confirmed via the
      analytical and spectral data. Compounds 1, 2, 3, 4, 5, 6, 7 and 9, were
      investigatedindividually in their free and PEG based nano-size hybrid forms as
      anticancer agents against three human cell lines:hepatocellular carcinoma cells
      (HepG2); breast cancer cells (MCF-7); and colon cancer cells (HCT116). The
      neutral redsupravital dye uptake assay was employed. Compound 6 in its PEG based
      nano-size form exhibited the best cytotoxiceffects against HepG2 and HCT116 cell
      lines, with IC50 values of 2.44 MUmol/l and 2.59 MUmol/l, respectively. In
      addition,it demonstrated a low IC50 value against MCF-7 (3.46MUmol/l) cells. This
      study introduced promising anticancer agentsacting through conversion into PEG
      based nanoparticles.

PMID- 28749625
TI  - Diphtheria, pertussis, and tetanus: evidence-based management of pediatric
      patients in the emergency department [digest].
AB  - Diphtheria, pertussis, and tetanus are potentially deadly bacterial infections
      that are largely preventable through vaccination, though they remain in the
      population. This issue reviews the epidemiology, pathophysiology, diagnosis, and
      current recommended emergency management of these conditions. Disease-specific
      medications, as well as treatment of the secondary complications, are examined in
      light of the best current evidence. Resources include obtaining diphtheria
      antitoxin from the United States Centers for Disease Control and Prevention and
      best-practice recommendations with regard to testing, involvement of government
      health agencies, isolation of the patient, and identification and treatment of
      close contacts. Most importantly, issues regarding vaccination and prevention are
      highlighted. [Points & Pearls is a digest of Pediatric Emergency Medicine
      Practice].

PMID- 28749626
TI  - Salivary MMP-1, MMP-2, MMP-3 and MMP-13 Levels in Patients with Oral Lichen
      Planus and Squamous Cell Carcinoma
AB  - The aim of present study was to evaluate salivary matrix metalloproteinase-1 (MMP
      1), MMP-2, MMP-3 andMMP-13 levels in patients with oral lichen planus (OLP) and
      squamous cell carcinomas (SCC) as well as in healthycontrols. Thirty cases of OLP
      (bilateral lesions, papular and reticular lesions, and Wickham lines) clinically
      andhistopathologically (group A), 30 with oral SCCs (group B), and 30 with no
      history of oral cancer, other lesions or lichenplanus (group C) were enrolled at
      the Department of Oral Medicine School of Dentistry, Zahedan, Iran.
      Unstimulatedwhole saliva was collected and laboratory measurement of salivary
      concentration of MMP-1, MMP-2, MMP-3 andMMP-13 was conducted by immuno-sorbent
      enzyme-linked methods. Data analysis was performed with Kruskal-Wallisand Mann
      Whitney tests and Pearson's correlation coefficients. In the present study, MMP-2
      and MMP-13 levels werehigher in oral SCC patients than in OLP and healthy
      individuals. More research is required to assess MMP links withtumor invasion.

PMID- 28749627
TI  - Acute kidney injury in pediatric patients: diagnosis and management in the
      emergency department [digest].
AB  - Pediatric acute kidney injury is a condition that is underdiagnosed among
      children seen in the emergency department, and it has been associated with
      significant morbidity and mortality, including increased risk for chronic kidney
      disease. The most common etiologies in pediatric patients are now known to be due
      to hypovolemia, sepsis, shock, and cardiac dysfunction. This issue compares 3
      classification systems for the diagnosis and staging of acute kidney injury and
      reviews the etiologies that lead to kidney injury in children. The management of
      pediatric acute kidney injury focuses on identifying patients at high risk,
      monitoring intravascular volume status, avoiding nephrotoxic medication exposure,
      and involving a pediatric nephrologist once acute kidney injury is diagnosed.
      [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].

PMID- 28749628
TI  - Circulating 25-Hydroxy Vitamin D Relative to Vitamin D Receptor Polymorphism
      after Vitamin D3 Supplementation in Breast Cancer Women: A Randomized, Double
      Blind Controlled Clinical Trial
AB  - Objective: The influence of vitamin D receptor (VDR) genetic variation on serum
      25-hydroxyvitamin D levels[25(OH)D] after vitamin D3 supplementation remains
      unclear. We aimed to investigate changes of 25(OH)D in arandomized, double-blind,
      placebo-controlled clinical trial, according to VDR genotype, after provision of
      vitamin D3 tobreast cancer cases for a 2-month period. Methods: Participants were
      assigned to two treatment arms: placebo (n = 28)and vitamin D3 supplementation (n
      =28). The supplementation group received 50,000 IU of vitamin D every week for
      2months. Blood samples were collected at baseline and after intervention to
      measure serum 25(OH)D3. Genotypes wereassessed for FokI, BsmI, ApaI, and TaqI
      polymorphisms. Results: After eight weeks supplementation, the interventiongroup
      showed a significant increase in the serum concentration of 25 (OH)D3 (28+/-2.6
      to 39+/-3.5; p=0.004). Subjectswere then classified into twelve subgroups
      according to different VDR genotypes. Subjects with ff/Ff, TT/Tt, and Bbgenotypes
      had significantly higher increases in serum 25(OH)D compared to those with FF,
      tt, and BB/bb genotypespost-intervention. Serum vitamin D3 levels with the AA
      genotype were lower than with aa/ Aa. No differences werefound among other
      subgroups. Conclusion: Vitamin D3 supplementation increases serum 25(OH)D in
      women withbreast cancer. Serum vitamin D3 in TT/Tt, ff/Ff, and Bb carriers was
      more responsive to vitamin D supplementationthan in those with FF/ff and tt
      genotypes. Other subgroups might gain less from vitamin D3 supplementation.

PMID- 28749629
TI  - Knowledge, Attitudes and Perceptions of Prostate Cancer among Male Staff of the
      University of Nigeria
AB  - Prostate cancer is the number one cancer in males in Africa, both in terms of
      incidence and mortality, accounting for40,000 (13%) male cancers and 28,000
      (11.3%) male cancer-associated deaths. In the developed world, the probabilityof
      being diagnosed with cancer is more than twice as high as in developing
      countries. In developing countries, mostcancer victims are diagnosed at late
      stage, with incurable tumors, pointing to the need for education schemes and
      betterdetection programs. This study assessed knowledge, attitudes and
      perceptions of prostate cancer among male staff ofthe University of Nigeria. This
      cross-sectional descriptive study was carried out with 655 male staff who agreed
      toparticipate and were recruited on giving oral consent. A self-administered
      questionnaire, written in English was used.The mean percentage knowledge score
      was 71.2%. Some 57.8% of respondents had a high knowledge level of
      prostatecancer. The mean percentage attitude score was 69.9%. More than half
      (60.8%, n = 397) of respondents had a positiveattitude towards prostate cancer
      screening and treatment. The mean percentage perception score was 60.0%. Morethan
      half (53.9%, n = 351) of respondents had a negative perception of prostate cancer
      screening and treatments. Thestaff of the University of Nigeria have appreciable
      knowledge and a positive attitude with regard to prostate cancer. Asignificant
      proportion of staff however, exhibited poor knowledge and negative attitudes and
      perceptions of prostatecancer screening and treatment.

PMID- 28749630
TI  - Influence of Training about Carcinogenic Effects of Hookah Smoking on the
      Awareness, Attitude, and Performance of Women
AB  - Background: Wrong attitudes and beliefs about the less carcinogenic effects of
      hookah smoking comparing tocigarette, easy availability, low cost, and other
      factors have caused that the usage of hookah smoking increase a lotin our
      country. Objective: This study has been done with the purpose of examining the
      influence of education aboutcarcinogenic effects of hookah smoking on the
      awareness, attitude, and performance of women who refer to the healthcareand
      medical treatment centers. Materials and Methods: At this semi experimental
      study, 60 women who refer to themedical and hygienic centers of Bushehr were
      placed in 3 educational groups based on simple accidental sampling.The tool for
      data collection was a questionnaire including demographic features, awareness,
      attitude, and performancemeasurement. Results: according to the results, the
      amount of awareness in the majority (48%) of participants aboutcarcinogenic
      effects of hookah smoking was in an average level. 100% of the participants had
      the awareness of over33.1% and their attitude toward hookah smoking was 100%
      positive that after the intervention it was reported 5%. Theparticipants'
      performance in hookah smoking before the intervention was only 25% desirable that
      after the interventionit was reported 73.3%. The results of Kolmogorov-Smirnov
      test also showed that the distribution of awareness, attitude,and performance was
      quite normal. Conclusion: according to the results, it's the society's basic need
      to warn peopleabout carcinogenic effects of hookah smoking by increasing people's
      awareness through media, holding training courses,showing movies, and training
      booklets.

PMID- 28749631
TI  - Human Papillomavirus (HPV) Genotype Distribution in Patients with Recurrent
      Respiratory Papillomatosis (RRP) in Iran
AB  - Background: Currently, recurrent respiratory papillomatosis (RRP), common
      laryngeal warts in the upper airwaysystems of children and adults are on the
      increase. Human papillomaviruses (HPVs) are suspected as causative agents.This
      study concerned HPV incidence and genotype distribution in Iranian RRP patients.
      Methods: Specimens werecollected from RRP patients referred to hospitals
      affiliated with Iran University of Medical Sciences, Tehran, Iran,from Dec 2014
      to Feb 2016 in a cross sectional study. After DNA extraction with an QIAamp(r)
      DNA FFPE TissueKit, conventional PCR was performed and products were sequenced.
      INNO-LiPA HPV Genotyping Extra assays asanother method for genotyping were
      conducted. CLC Main Workbench 5 and MEGA6 software as well as SPSS v.20were used
      for further analysis. Results: Of the total of 12 patients, 6 (50%) were male.
      Total mean age (y) +/- SD was9.8+/-6.3. All RRP patients suffered from HPV
      infection, with HPV-6 found in 75% (9/12) and HPV-11 in 16.7% (2/12)and one co
      infection by both HPV-6 and 11. Statistically, there were no correlations between
      demographic variables andHPV infection. Conclusion: The major cause of RRP is HPV
      genotypes 6 and 11 increasing the risk of a requirementfor medical interventions.
      Broader studies are needed to clarify the major risk factors in RRP patients.

PMID- 28749635
TI  - Awareness of Breast Cancer among Female Care Givers in Tertiary Cancer Hospital,
      China
AB  - Objective: Breast cancer is a worldwide public health issue and most common
      cancer diagnosed among womenincluding China, where advanced stages at diagnosis
      appears to be increasing and an ever-rising incidence twice as fastas global
      rates. The study was conducted to describe the awareness of breast cancer and
      associated factors among caregiver women in tertiary Cancer Hospital, China.
      Methods: Institutional based cross-sectional study was conductedamong 261 women
      selected by systematic random sampling. Information provided by the participants
      was convertedinto awareness scores for analysis using SPSS version 23. Awareness
      scores were dichotomized in to 'good awarenessand 'poor awareness' taking median
      score=11 as the cut-off point. Data analysis was performed using the
      binarylogistic regression. A p-value of <0.05 was considered statistically
      significant. Result: The study showed that 46.7%of the respondents had good
      awareness. Breast lump was the most commonly known symptom of cancer by 61.7%
      ofthe respondents. Slightly more than half of the study participants acknowledged
      having a past history of breast cancer,drinking alcohol and having close relative
      with breast cancer as potential risk factors for breast cancer (63.6%, 58.6%,and
      55.6% respectively). Nevertheless, a vast majority of the study participants were
      unable to appreciate modifiablerisk factors of the disease. More than half of the
      participants had never/rarely checked their breasts and all of theparticipants
      wrongly answered breast cancer knowledge age related risk. Awareness level was
      significantly associatedwith entertainment preference (OR=3.57; 95%CI=1.71, 7.44)
      and residence setting areas (OR=2.4; 95%CI=1.04,5.69). Conclusion: The study
      indicated suboptimal awareness while entertainment preference and residence
      settingwere significantly associated with awareness level. Public awareness
      campaigns should be made by dissemination ofinformation about breast cancer
      through health education and printed Medias with great emphases on women livingin
      rural areas.

PMID- 28749636
TI  - Impact of Cancer Awareness Drive on Generating Understanding and Improving
      Screening Practices for Breast Cancer: a Study on College Teachers in India
AB  - Background: Breast cancer is the most common cancer among women in India and most
      present at advancedstage. Although early detection is the only way to reduce
      morbidity and mortality, people have a very low awarenessabout breast cancer
      signs and symptoms and screening practices. The purpose of this study was to
      assess the level ofawareness and impact of awareness programs in adoption of safe
      practices in prevention and early detection. Methods:This assessment was part of
      a pink chain campaign on cancer awareness. During events from 2011 to 2015 at
      variouswomen colleges in different parts in India, a pre-test of knowledge
      related to breast cancer was followed by an awarenessprogram. Post-tests using
      the same questionnaire were conducted at the end of the interactive sessions, at
      6 months andafter1 year. Results: A total of 872 out of 985 teachers participated
      in the study (overall response rate of 88.5 %). Meanage of the study population
      was 41.6 years (range 28-59 yrs). There was a significant increase in level of
      knowledgeregarding breast cancer at 6 months and this was sustained at 1 year.
      Adoption of breast self-examination (BSE) wassignificantly more frequent in
      comparison to CBE and mammography. Magazines and newspapers were sources
      forknowledge regarding screening tests for breast cancer for more than 60% of
      teachers. Regarding post-awareness at 6months and 1 year, there was a significant
      change in alcohol and smoking habits. Major reasons came out to be ignorance(83%)
      at the start of the campaign which was changed to lack of time (37.7%), lethargic
      attitude (32.2 %) and lack oftime (31.5 %) at 6 months and same at 1 year also.
      Conclusions: With our awareness program there was a significantincrease in level
      of knowledge regarding breast cancer at 6 months and this was sustained at 1
      year. Adoption of BSEwas significantly greater in comparison to CBE, mammography.
      To inculcate safe lifestyle practices in people, awarenessprogrammes such as pink
      chain campaigns should be conducted more widely and frequently.

PMID- 28749641
TI  - Factors Affecting Mental Patients' Behaviors and Attitudes Regarding Smoking
AB  - Background: Patients with mental health problems are in high risk to develop
      addiction, since smoking incidenceis three times higher than that of the general
      population. The aim of the study was to investigate the factors affectingmental
      health patients' smoking habits. Methods: The sample of study were 356 patients
      out of 403 initially approached,with 142 hospitalized in hospital facilities and
      214 in community settings. The "Smoking in psychiatric hospitals" andGeneral
      Health Questionnaire (GHQ-28) questionnaires were used. A principal component
      analysis was performedusing the correlation coefficients of the various variables
      and an orthogonal varimax rotation, in order to interpret theseven factors
      emerging. Among the variables the most important factors appeared to be the type
      of healthcare facility,legal status, depression and age. Results: The type of
      healthcare facility was correlated to demographic characteristics,clinical
      features, psychopathology and functionality, but also to the attitudes and
      behaviors related to smoking. Morespecifically, the in-hospital patients were
      heavier smokers, about 90% of the patients said they would consider
      quittingsmoking. The various variables had only a small effect on the intention
      to quit smoking. The comparison of the coefficientsof determination of each
      variable, showed that age had the strongest effect (R2=0.152), while the GHQ D
      subscale(severe depression) had the least significant effect (R2=0.023). From all
      (7) factors, it appears that hospitalization waspositively correlated with factor
      5 and negatively with the factors 2, 3 and 6, legal status (commitment order)
      negativelywith factors 1 and 4, while depression (or consuming antidepressants)
      positively factor 4 and negatively to factors 1and 3. Finally, age was the only
      variable that is associated with the agent 7. Conclusions: Patients are
      permissive tostaff's smoking in the healthcare facility and may resist attempts
      to restrict it. It is important that these conclusions aretaken into account in
      any systematic attempt to limit smoking within mental health settings.

PMID- 28749642
TI  - Combination Therapy with Low Copper Diet, Penicillamine and Gamma Knife
      Radiosurgery Reduces VEGF and IL-8 In Patients with Recurrent Glioblastoma
AB  - Purpose: Vascular Endothelial Growth Factor (VEGF) and interleukin-8 (IL-8)
      appear important in tumor growth. Inthis study, we have investigated the effect
      of copper reduction along with gamma knife radiosurgery on IL-8 and VEGFin
      patients with recurrent glioblastoma multiforme (GBM). Materials and Methods: In
      a 3-month randomized clinicaltrial, patients with recurrent GBM were allocated
      randomly between intervention and placebo groups. Radiosurgerywas performed for
      both groups (Reference dose: 16-18 Gray, in one fraction). The intervention group
      received lowcopper diet and penicillamine while the patients in the placebo group
      continued with their usual diet. VEGF and IL-8were measured at baseline and the
      end of intervention. Results: VEGF in intervention group significantly
      reducedcompared to placebo group (Mean +/- SD, 4.5+/-1.91 vs. 7.8+/-3.21;
      P<0.001). IL-8 in intervention group decreasedcompared to placebo group but not
      significant (2.7+/-1.91 vs. 3.2+/-3.20; P=0.49). We also detected a significant
      positivecorrelation between serum copper and VEGF (r=0.57; P<0.05) and a negative
      correlation between KPS and serumcopper. Discussion: Our results could reflect
      that low copper diet and penicillamine may decrease serum VEGF inpatients who
      underwent gamma knife radiosurgery for recurrent glioblastoma multiforme.

PMID- 28749643
TI  - Non Communicable Disease Risk Factors and their Trends in India
AB  - Background: India is a populous country of about 1.3 billion. Non communicable
      diseases (NCDs) contribute toaround 5.87 million (60%) of all deaths in India.
      Hence, the objectives of this paper are to find baseline informationon different
      NCD risk factors coverage and to determine their trends in India. Methods: For
      this systematic review,PubMed, Google and different surveillance systems were
      searched. Of the search results, 41 papers/survey reports wereeventually assessed
      for eligibility. National and state representative data on NCD risk factors (for
      the major NCDs likecardiovascular diseases, chronic respiratory disease, cancer
      and diabetes) having World Health Organization(WHO)indicator definitions,
      covering rural and urban population, were included in the study. Thereafter,
      state-wise populationproportion was added and divided by the total Indian
      population to determine the percentage of population coverage foreach risk factor
      by the surveys. Also, the old and current data of the periodic surveys were
      compared to assess prevalencetrends. Results: Various national/state level
      surveys in India include single or multiple risk factors. Nationwide coverageis
      available for tobacco use, alcohol drinking, raised blood pressure and overweight
      and obesity. Periodic NationalFamily Health Surveys provide information on
      selected risk factors during 2005-16 among adults aged 15-49 years.An overall
      significant increase was noted in overweight and obesity while decline was noted
      in tobacco and alcoholuse during the same period. From GATS 1 (2009-10) to 2
      (2016-17) also, the prevalence of tobacco consumptiondecreased in India.
      Conclusion: India has a much delayed response on NCD risk factors surveillance
      and informationof the same are sporadic and incomplete. In order to increase
      information comprehensiveness, standard WHO NCDrisk factors questions must be
      incorporated in the ongoing surveys. India should also plan for cost and time
      effectiveNCD surveillance system.

PMID- 28749644
TI  - The Cost-Effectiveness of Quadrivalent Human Papillomavirus Vaccination in
      Indonesia
AB  - Objective: National cervical cancer prevention program has been initiated in
      Indonesia since April 2015 and theministry of health has started efforts to
      integrate the HPV Vaccine in the national immunization program since Q42015.
      Thus, it becomes important to analyze the cost-effectiveness of HPV vaccine. The
      objective of this model is toexamine the potential long-term epidemiologic and
      economic impact of quadrivalent HPV(qHPV;6/11/16/18) vaccinationprogram in
      Indonesia. Methods: A previously validated transmission dynamic model was used to
      estimate the long-termepidemiologic and economic consequences of quadrivalent HPV
      vaccination by comparing cost-effectiveness of 2dose qHPV vaccination strategy
      for girls 11-12 years old (with or without catch up; catch up dose for 12-26
      years)versus Screening Only (Pap Smear) for reducing cost related to HPV type
      6,11,16,18 (cervical cancer, CIN 1, CIN2/3, and genital warts). Costs of an HPV
      disease episode-of-care (diagnosis and treatment) were calculated for basecase
      analysis using local Indonesian cost. Result: 2-dose qHPV vaccination strategies
      without catch up reduce theoverall incidence of HPV 16/18-related cervical cancer
      relative to screening by 54.4% over the 100 year followingvaccine introduction.
      Likewise, vaccination strategies reduce the incidence of HPV type 16/18 CIN 2/3,
      CIN 1 by69.1% and 71.8% respectively, also reducing HPV type 6/11 CIN 1, genital
      warts in female, genital warts in male by82.9%,84.2%,82.1% respectively, at this
      time point. From total reduction of health care cost, 67.1% attributable
      fordiseases caused by HPV type 16/18 and 32.9% attributable for diseases caused
      by HPV type 6/11. Without catch up,cost/QALY would be $450/year. However catch-up
      strategy is more cost effective versus vaccinates 12-year-old girlsonly; with
      cost/QALYs would be $390/year. Conclusion: HPV 6/11/16/18 vaccination of females
      in Indonesia are1) substantially reduce genital warts, CIN, and cervical cancer;
      2) improve quality of life, and 3) with the IndonesiaGDP of USD 3,531.80 in 2014
      , Cost/QALYs result with or without catch up is considered very cost-effective
      whenimplemented; however with catch up, the cost/QALY can be better.

PMID- 28749650
TI  - Interface Electrode Morphology Effect on Carrier Concentration and Trap Defect
      Density in an Organic Photovoltaic Device.
AB  - Formation of Schottky barrier contact (SBC) leads reconstruction of charges at
      the metal/semiconductor (MS) interface because of the wave function overlap
      between semiconductor and metal contact. Not only is the Schottky barrier contact
      formation a signature of the material's work function, but also it is sensitive
      to the interface trap states, the crystal orientation of the interacting
      materials, and other interface properties. In this work, the effect of aluminum
      cathode morphology on the polymer Schottky diode and bulk heterojunction (BHJ)
      photovoltaic device performance is studied. The electron collecting contacts in
      Schottky diode and BHJ device have been deposited using aluminum in pellet and
      nanoparticle forms. Devices fabricated by using Al nanoparticle showed
      improvement in dark as well as photocurrent density. Significant enhancement in
      JSC leads to overall improved power conversion efficiency. Enhanced performance
      in Schottky structured diode and OPV device have been correlated with electrode
      microstructure and its interface properties such as improved electrically active
      contact and enhanced charge transport. Electrical conductivity is discussed based
      on enhanced electrical coherence across organic semiconductor and electrode
      interface. Therefore, the contribution of electrical enhancement leads to
      improvement in short-circuit current density (JSC) in BHJ solar cell which is due
      to reduced trap density. Further, PCE was correlated with the density of
      interface trap states studied by drive level capacitance profiling technique.

PMID- 28749651
TI  - Liquid Chromatography-Tandem Mass Spectrometry for the Quantification of Tobacco
      Specific Nitrosamine-Induced DNA Adducts in Mammalian Cells.
AB  - Quantification of DNA lesions constitutes one of the main tasks in toxicology and
      in assessing health risks accompanied by exposure to carcinogens. Tobacco
      specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'
      nitrosonornicotine (NNN) can undergo metabolic transformation to give a reactive
      intermediate that pyridyloxobutylates nucleobases and phosphate backbone of DNA.
      Here, we reported a highly sensitive method, relying on the use of nanoflow
      liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry (nLC
      nESI-MS/MS), for the simultaneous quantifications of O6-[4-(3-pyridyl)-4-oxobut-1
      yl]-2'-deoxyguanosine (O6-POBdG) as well as O2- and O4-[4-(3-pyridyl)-4-oxobut-1
      yl]-thymidine (O2-POBdT and O4-POBdT). By using this method, we measured the
      levels of the three DNA adducts with the use of 10 MUg of DNA isolated from
      cultured mammalian cells exposed to a model pyridyloxobutylating agent, 4
      (acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc). Our results
      demonstrated, for the first time, the formation of O4-POBdT in naked DNA and in
      genomic DNA of cultured mammalian cells exposed with NNKOAc. We also revealed
      that the levels of the three lesions increased with the dose of NNKOAc and that
      O2-POBdT and O4-POBdT could be subjected to repair by the nucleotide excision
      repair (NER) pathway. The method reported here will be useful for investigations
      about the involvement of other DNA repair pathways in the removal of these
      lesions and for human toxicological studies in the future.

PMID- 28749652
TI  - Evaluating Benthic Recovery Decades after a Major Oil Spill in the Laurentian
      Great Lakes.
AB  - The long-term effects of oil spills on freshwater organisms have been little
      studied. In 1950, a large oil spill (10 million L) covered the harbor area of
      Parry Sound, Ontario, the deepest port in the Laurentian Great Lakes. Ecological
      impacts were not studied at the time, but 25 years later three-quarters of the
      Chironomus cucini larvae (Insecta, Diptera, Chironomidae) living in the harbor
      area were reported to be deformed. We returned six decades after the spill and
      found that the frequency of deformities had returned to background levels and
      that the community of burrowing invertebrates has largely recovered. By dating
      sediment cores and measuring the depth distribution of oils, we conclude that,
      although the oil persists six decades after the spill, sufficient uncontaminated
      sediment has covered the oil thereby putting it out of reach of most burrowing
      animals. Provided that the sediment remains undisturbed, the buried oil is
      unlikely to exert further negative effects on the biota in spite of the fact that
      it will likely persist for centuries.

PMID- 28749653
TI  - Measurement and Surface Complexation Modeling of U(VI) Adsorption to Engineered
      Iron Oxide Nanoparticles.
AB  - Surface-functionalized magnetite nanoparticles have high capacity for U(VI)
      adsorption and can be easily separated from the aqueous phase by applying a
      magnetic field. A surface-engineered bilayer structure enables the stabilization
      of nanoparticles in aqueous solution. Functional groups in stearic acid (SA),
      oleic acid (OA), and octadecylphosphonic acid (ODP) coatings led to different
      adsorption extents (SA~ OA > ODP) under the same conditions. The impact of water
      chemistry (initial loading of U(VI), pH, and the presence of carbonate) has been
      systematically examined for U(VI) adsorption to OA-coated nanoparticles. A
      diffuse double layer surface complexation model was developed for surface
      functionalized magnetite nanoparticles that could simulate both the measured
      surface charge and the U(VI) adsorption behavior at the same time. With a small
      set of adsorption reactions for uranyl hydroxide and uranyl carbonate complexes
      to surface sites, the model can successfully simulate the entire adsorption data
      set over all uranium loadings, pH values, and dissolved inorganic carbon
      concentrations. The results show that the adsorption behavior was related to the
      changing U(VI) species and properties of surface coatings on nanoparticles. The
      model could also fit pH-dependent surface potential values that are consistent
      with measured zeta potentials.

PMID- 28749654
TI  - Decomposition Mechanism of C5F10O: An Environmentally Friendly Insulation Medium.
AB  - SF6, the most widely used electrical-equipment-insulation gas, has serious
      greenhouse effects. C5F10O has attracted much attention as an alternative gas in
      recent two years, but the environmental impact of its decomposition products is
      unclear. In this work, the decomposition characteristics of C5F10O were studied
      based on gas chromatography-mass spectrometry and density functional theory. We
      found that the amount of decomposition products of C5F10O, namely, CF4, C2F6,
      C3F6, C3F8, C4F10, and C6F14, increased with increased number of discharges.
      Under a high-energy electric field, the C-C bond of C5F10O between carbonyl
      carbon and alpha-carbon atoms was most likely to break and generate CF3CO*, C3F7*
      or C3F7CO*, CF3* free radicals. CF3*, and C3F7* free radicals produced by the
      breakage more easily recombined to form small molecular products. By analyzing
      the ionization parameters, toxicity, and environmental effects of C5F10O and its
      decomposition products, we found that C5F10O gas mixtures exhibit great
      decomposition and environmental characteristics with low toxicity, with great
      potential to replace SF6.

PMID- 28749655
TI  - Cyclometalated Iridium(III)-Complex-Based Micelles for Glutathione-Responsive
      Targeted Chemotherapy and Photodynamic Therapy.
AB  - The integration of chemotherapy and photodynamic therapy (PDT) in a single
      delivery system is highly desirable for enhancing anticancer therapeutic
      efficacy. Herein, two cyclometalated Ir(III) complex-constructed micelles FIr-1
      and FIr-2 were demonstrated for glutathione (GSH) activated targeted chemotherapy
      and PDT. The cyclometalated Ir(III) complexes were prepared by conjugating
      phosphorescent Ir(III) compounds with chemotherapeutic drug camptothecin (CPT)
      through GSH responsive disulfide bond linkages, and the Ir(III) complexes were
      then assembled with amphiphilic surfactant pluronic F127 via noncovalent
      encapsulation to afford micelles. The surfaces of the micelles were further
      decorated with folic acid as a targeting group. The micelles showed intense
      fluorescence that renders them with excellent real-time imaging capability. The
      release of free anticancer drug CPT from the micelles was realized through GSH
      activated disulfide bond cleavage in tumor cells. In addition, the micelles were
      capable of generating singlet oxygen used for PDT upon visible light irradiation.
      On account of having folic acid targeting ligand, the micelles displayed greater
      cellular accumulation in folate receptor (FR) overexpressed HeLa cells than FR
      low-expressed MCF-7 cells, leading to selective cancer cell killing effect. As
      compared with solo therapeutic systems, the micelles with targeted combinational
      chemotherapy and PDT presented superior potency and efficacy in killing tumor
      cells at a low dosage. On the basis of these findings, the multifunctional
      micelles could serve as a versatile theranostic nanoplatform for cancer cell
      targeted imaging and combinational therapy.

PMID- 28749656
TI  - Development of Artificial Riboswitches for Monitoring of Naringenin In Vivo.
AB  - Microbial strains are considered promising hosts for production of flavonoids
      because of their rapid growth rate and suitability for large-scale manufacturing.
      However, productivity and titer of current recombinant strains still do not meet
      the requirements of industrial processes. Genetically encoded biosensors have
      been applied for high-throughput screening or dynamic regulation of biosynthetic
      pathways for enhancing the performance of microbial strains that produce valuable
      chemicals. Currently, few protein sensor-regulators for flavonoids exist. Unlike
      the protein-based trans-regulating controllers, riboswitches can respond to their
      ligands faster and eliminate off-target effects. Here, we developed artificial
      riboswitches that activate gene expression in response to naringenin, an
      important flavonoid. RNA aptamers for naringenin were developed using SELEX and
      cloned upstream of a dual selectable marker gene to construct a riboswitch
      library. Two in vivo selection routes were applied separately to the library by
      supplementing naringenin at two different concentrations during enrichments to
      modulate the operational ranges of the riboswitches. The selected riboswitches
      were responsive to naringenin and activated gene expression up to 2.91-fold.
      Operational ranges of the riboswitches were distinguished on the basis of their
      selection route. Additionally, the specificity of the riboswitches was assessed,
      and their applicability as dynamic regulators was confirmed. Collectively, the
      naringenin riboswitches reported in this work will be valuable tools in metabolic
      engineering of microorganisms for the production of flavonoids.

PMID- 28749657
TI  - Deep Metaproteomics Approach for the Study of Human Microbiomes.
AB  - Host-microbiome interactions have been shown to play important roles in human
      health and diseases. Most of the current studies of the microbiome have been
      performed by genomic approaches through next-generation sequencing. Technologies,
      such as metaproteomics, for functional analysis of the microbiome are needed to
      better understand the intricate host-microbiome interactions. However,
      significant efforts to improve the depth and resolution of gut metaproteomics are
      still required. In this study, we combined an efficient sample preparation
      technique, high resolution mass spectrometry, and metaproteomic bioinformatics
      tools to perform ultradeep metaproteomic analysis of human gut microbiome from
      stool. We reported the deepest analysis of the microbiome to date with an average
      of 20 558 protein groups identified per sample analysis. Moreover, strain
      resolution taxonomic and pathway analysis using deep metaproteomics revealed
      strain level variations, in particular for Faecalibacterium prausnitzii, in the
      microbiome from the different individuals. We also reported that the human
      proteins identified in stool samples are functionally enriched in extracellular
      region pathways and in particular those proteins involved in defense response
      against microbial organisms. Deep metaproteomics is a promising approach to
      perform in-depth microbiome analysis and simultaneously reveals both human and
      microbial changes that are not readily apparent using the standard genomic
      approaches.

PMID- 28749658
TI  - Effect of Salt on the Uranyl Binding with Carbonate and Calcium Ions in Aqueous
      Solutions.
AB  - The Ca2(UO2)(CO3)3 complex has been shown to be the dominant species of uranyl in
      different aqueous environments, and thermodynamic data of the complexation have
      been measured accurately recently. However, a detailed understanding of the
      binding processes with explicit consideration of the water molecules in the
      presence of common salt ions such as Na+ and Cl- has been lacking. Here we use
      classical molecular dynamics combined with umbrella sampling to map the complete
      binding processes and their free-energy profiles leading to formation of the
      Ca2(UO2)(CO3)3 complex from UO22+, CO32-, and Ca2+ in an aqueous NaCl solution to
      simulate the seawater conditions. We find that the presence of Na+ ions affects
      the binding between UO22+ and CO32- as well as between [(UO2)(CO3)3]4- and Ca2+
      by changing the coordination mode of carbonate to UO22+. The free energies of
      binding from our simulations are in good agreement with the experimental data for
      both pure water and the NaCl solution. Our work shows that free-energy
      simulations based on classical molecular dynamics simulations can be a useful
      tool to examine the atomistic process of the ligand binding to form the
      Ca2(UO2)(CO3)3 complex under different aqueous environments and that the presence
      of common ions can impact the complexation chemistry of uranyl.

PMID- 28749659
TI  - In Situ Methylene Capping: A General Strategy for Efficient Stereoretentive
      Catalytic Olefin Metathesis. The Concept, Methodological Implications, and
      Applications to Synthesis of Biologically Active Compounds.
AB  - In situ methylene capping is introduced as a practical and broadly applicable
      strategy that can expand the scope of catalyst-controlled stereoselective olefin
      metathesis considerably. By incorporation of commercially available Z-butene
      together with robust and readily accessible Ru-based dithiolate catalysts
      developed in these laboratories, a large variety of transformations can be made
      to proceed with terminal alkenes, without the need for a priori synthesis of a
      stereochemically defined disubstituted olefin. Reactions thus proceed with
      significantly higher efficiency and Z selectivity as compared to when other Ru-,
      Mo-, or W-based complexes are utilized. Cross-metathesis with olefins that
      contain a carboxylic acid, an aldehyde, an allylic alcohol, an aryl olefin, an
      alpha substituent, or amino acid residues was carried out to generate the desired
      products in 47-88% yield and 90:10 to >98:2 Z:E selectivity. Transformations were
      equally efficient and stereoselective with a ~70:30 Z-:E-butene mixture, which is
      a byproduct of crude oil cracking. The in situ methylene capping strategy was
      used with the same Ru catechothiolate complex (no catalyst modification
      necessary) to perform ring-closing metathesis reactions, generating 14- to 21
      membered ring macrocyclic alkenes in 40-70% yield and 96:4-98:2 Z:E selectivity;
      here too, reactions were more efficient and Z-selective than when the other
      catalyst classes are employed. The utility of the approach is highlighted by
      applications to efficient and stereoselective syntheses of several biologically
      active molecules. This includes a platelet aggregate inhibitor and two members of
      the prostaglandin family of compounds by catalytic cross-metathesis reactions,
      and a strained 14-membered ring stapled peptide by means of macrocyclic ring
      closing metathesis. The approach presented herein is likely to have a notable
      effect on broadening the scope of olefin metathesis, as the stability of
      methylidene complexes is a generally debilitating issue with all types of
      catalyst systems. Illustrative examples of kinetically controlled E-selective
      cross-metathesis and macrocyclic ring-closing reactions, where E-butene serves as
      the methylene capping agent, are provided.

PMID- 28749660
TI  - Low-Dimensional Nitridosilicates Grown from Ca/Li Flux: Void Metal Ca8In2SiN4 and
      Semiconductor Ca3SiN3H.
AB  - Reactions of indium and silicon with lithium nitride in Ca/Li flux produce two
      new nitridosilicates: Ca8In2SiN4 (orthorhombic, Ibam; a = 12.904(1) A, b =
      9.688(1) A, c = 10.899(1) A, Z = 4) and Ca3SiN3H (monoclinic, C2/c; a = 5.236(1)
      A, b = 10.461(3) A, c = 16.389(4) A, beta = 91.182(4) degrees , Z = 8).
      Ca8In2SiN4 features isolated [SiN4]8- units and indium dimers surrounded by
      calcium atoms. Ca3SiN3H features infinite chains of corner-sharing SiN4
      tetrahedra and distorted edge-sharing H@Ca6 octahedra. Optical properties and
      band structure calculations indicate that Ca8In2SiN4 is a void metal with calcium
      and indium states at the Fermi level and Ca3SiN3H is a semiconductor with a band
      gap of 3.1 eV.

PMID- 28749661
TI  - Determination of the Degree of Substitution of Cationic Guar Gum by Headspace
      Based Gas Chromatography during Its Synthesis.
AB  - This study reports on a headspace-based gas chromatography (HS-GC) technique for
      determining the degree of substitution (DS) of cationic guar gum during the
      synthesis process. The method is based on the determination of 2,3
      epoxypropyltrimethylammonium chloride in the process medium. After a modest
      pretreatment procedure, the sample was added to a headspace vial containing
      bicarbonate solution for measurement of evolved CO2 by HS-GC. The results showed
      that the method had a good precision (relative standard deviation of <3.60%) and
      accuracy for the 2,3-epoxypropyltrimethylammonium chloride measurement, with
      recoveries in the range of 96-102%, matching with the data obtained by a
      reference method, and were within 12% of the values obtained by the more arduous
      Kjeldahl method for the calculated DS of cationic guar gum. The HS-GC method
      requires only a small volume of sample and, thus, is suitable for determining the
      DS of cationic guar gum in laboratory-scale process-related applications.

PMID- 28749662
TI  - Influence of Different Fermentation Strategies on the Phenolic Profile of
      Bilberry Wine (Vaccinium myrtillus L.).
AB  - Polyphenol rich and especially anthocyanin rich berries like bilberries
      (Vaccinium myrtillus L.) and derived products such as wine have enjoyed
      increasing popularity. During winemaking and aging, the phenolic profile
      undergoes distinct changes, a phenomenon that has been well investigated in grape
      wine but not in bilberry wine. The present study determined the influence of
      different fermentation strategies including various pre- and postfermentative
      heating and cooling concepts on the phenolic profile of bilberry wine. Besides
      significant differences in total anthocyanin and tannin concentrations, the
      different fermentation strategies resulted in distinguishable anthocyanin
      profiles. A very fast aging manifested by a rapid decrease in monomeric
      anthocyanins of up to 98% during a 12 week storage and a coincident formation of
      polymeric pigments and pyranoanthocyanins was observed. Several well-known
      processes associated with production and aging of wine were much more pronounced
      in bilberry wine compared to grape wine.

PMID- 28749663
TI  - Iodide-Mediated Synthesis of Spirooxindolo Dihydrofurans from Iodonium Ylides and
      3-Alkylidene-2-oxindoles.
AB  - An iodide-mediated reaction between cyclic iodonium ylides of 1,3-dicarbonyls and
      3-alkylidene-2-oxindoles results in 3H-spiro[furan-2,3'-indolin]-2'-ones. The
      reaction was tolerant to substitutions on both the alkylidene and ylide
      substrates and provided access to 19 new, densely functionalized polycyclic
      spirocycles in typically high yield.

PMID- 28749664
TI  - Matildite Contact with Media: First-Principles Study of AgBiS2 Surfaces and
      Nanoparticle Morphology.
AB  - Motivated by the interest in AgBiS2 material for solar light harvesting
      applications, a detailed bulk first-principles quantum mechanical study of its
      surface properties is presented. Density functional theory based calculations
      with the Perdew-Burke-Ernzerhof functional have been carried out for different
      surface orientations and terminations of the matildite polymorph. From the
      results, two particularly stable facets are predicted to dominate Wulff shaped
      AgBiS2 nanoparticles. These are the (001) type nonpolar surface and the (111)
      polar terminations where facets are exposed containing solely Ag or S atoms. The
      Wulff equilibrium shape is predicted to be a cube with only two edges capped.
      This particular shape explains a previously reported surface enrichment of Ag
      with respect to Bi of ~1.5. The (001) surfaces display an ionic character similar
      to bulk AgBiS2, with a low work function of 4.31 eV, although the inspection of
      the density of states (DOS) reveals a bandgap increased by 0.3 eV compared to
      bulk. This surface effect could explain the bulk wavelength overestimation of the
      absorption coefficient decay, as previously determined. Last but not least, the
      DOS of the (111) polar termination reveals a metallic character, where Fermi
      level is located below that on the (001) surfaces. Possible implications of the
      different electronic structure of these surfaces in the reported photoactivity
      are discussed.

PMID- 28749665
TI  - Summary of the ACS Symposium on Public Health Perspectives of Mycotoxins in Food.
AB  - A symposium entitled "Public Health Perspectives of Mycotoxins in Food" was held
      at the 251st American Chemical Society (ACS) Meeting in March 2016 in San Diego,
      CA, and was sponsored by the ACS Division of Agricultural and Food Chemistry. The
      purpose of the symposium was to convene the leading mycotoxin researchers
      throughout the world to discuss the current state of knowledge as well as
      research needs with respect to evaluating the toxicological properties of
      mycotoxins and ways to detect, control, and reduce human and animal exposure to
      these natural toxins. A total of 23 presentations were delivered by speakers
      representing academic, government, and industrial institutions from North
      America, Europe, Asia, and Africa. The presentations covered such diverse topics
      as a historical perspective on the discovery of the major fungal toxins,
      occurrence of mycotoxins in food and feed, toxicological properties of mycotoxins
      and their influence on public health, analytical methods for mycotoxins, pre- and
      postharvest control of mycotoxins, and regulatory aspects. This paper is intended
      to provide a brief summary of the presentations as well as a record of the
      proceedings of the symposium.

PMID- 28749666
TI  - Substituted N-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are
      Valuable Antitubercular Candidates that Evade Innate Efflux Machinery.
AB  - Tuberculosis remains one of the deadliest infectious diseases in the world, and
      the increased number of multidrug-resistant and extremely drug-resistant strains
      is a significant reason for concern. This makes the discovery of novel
      antitubercular agents a cogent priority. We have previously addressed this need
      by reporting a series of substituted 2-aminothiazoles capable to inhibit the
      growth of actively replicating, nonreplicating persistent, and resistant
      Mycobacterium tuberculosis strains. Clues from the structure-activity
      relationships lining up the antitubercular activity were exploited for the
      rational design of improved analogues. Two compounds, namely N-phenyl-5-(2-(p
      tolylamino)thiazol-4-yl)isoxazole-3-carboxamide 7a and N-(pyridin-2-yl)-5-(2-(p
      tolylamino)thiazol-4-yl)isoxazole-3-carboxamide 8a, were found to show high
      inhibitory activity toward susceptible M. tuberculosis strains, with an MIC90 of
      0.125-0.25 MUg/mL (0.33-0.66 MUM) and 0.06-0.125 MUg/mL (0.16-0.32 MUM),
      respectively. Moreover, they maintained good activity also toward resistant
      strains, and they were selective over other bacterial species and eukaryotic
      cells, metabolically stable, and apparently not susceptible to the action of
      efflux pumps.

PMID- 28749667
TI  - BACE-1 Inhibitors: From Recent Single-Target Molecules to Multitarget Compounds
      for Alzheimer's Disease.
AB  - The amyloid hypothesis has long been the central dogma in drug discovery for
      Alzheimer's disease (AD), leading to many small-molecule and biological drug
      candidates. One major target has been the beta-site amyloid-precursor-protein
      cleaving enzyme 1 (BACE-1), with many big pharma companies expending great
      resources in the search for BACE-1 inhibitors. The lack of efficacy of
      verubecestat in mild-to-moderate AD raises important questions about the timing
      of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in
      AD treatment. It also suggests new possibilities for discovering BACE-1-targeted
      compounds with more complex mechanisms of actions and improved efficacy. Herein,
      we review the major advances in BACE-1 drug discovery, from single-target small
      molecule inhibitors to multitarget compounds. We discuss these compounds as
      innovative tools for better understanding the complexity of AD and for
      identifying efficacious drug candidates to treat this devastating disease.

PMID- 28749668
TI  - Copper-Catalyzed Oxidative Cross-Dehydrogenative Coupling/Oxidative
      Cycloaddition: Synthesis of 4-Acyl-1,2,3-Triazoles.
AB  - A copper-catalyzed three-component reaction of methyl ketones, organic azides,
      and various one-carbon (C1) donors was developed that provides 4-acyl-1,2,3
      triazoles in moderate to good yields. While DMF, DMA, TMEDA, or DMSO can serve as
      the C1 donor, best yields were obtained using DMF. The transformation is proposed
      to proceed via an oxidative C-H/C-H cross-dehydrogenative coupling followed by an
      oxidative 1,3-dipolar cycloaddition.

PMID- 28749669
TI  - Thermal Degradation of Major Gomphrenin Pigments in the Fruit Juice of Basella
      alba L. (Malabar Spinach).
AB  - Generation of decarboxylated and dehydrogenated gomphrenins during heating of
      Basella alba L. fruit juice containing high levels of betacyanin pigments was
      monitored by LC-DAD-ESI-MS/MS. The presence of principal decarboxylation
      products, 2-, 17-, and 2,17-decarboxy-gomphrenins, their diastereomers, as well
      as minor levels of their dehydrogenated derivatives are reported. In addition,
      determination of molecular masses of decarboxylated gomphrenins by high
      resolution mass spectrometry (LCMS-IT-TOF) was performed. Enzymatic
      deglucosylation of decarboxylated and dehydrogenated gomphrenins resulted in the
      generation of betanidin diagnostic derivatives for further identification
      processes. In addition, experiments were conducted to prove that the position of
      glucosylation of the chromophoric part of betacyanins (betanidin part) has
      decisive influence on different chromatographic properties of their
      decarboxylated derivatives.

PMID- 28749670
TI  - Bioactive Azaphilone Derivatives from the Fungus Talaromyces aculeatus.
AB  - Six new azaphilone derivatives, talaraculones A-F (1-6), together with five known
      analogues (7-11), were obtained from the saline soil-derived fungus Talaromyces
      aculeatus. The absolute configurations of 1 and 6 were assigned by quantum
      chemical calculations of the electronic circular dichroism (ECD) spectra.
      Compounds 1 and 5 represent the first reported azaphilone derivatives with a C4
      aliphatic side chain and a methylal group at C-3, respectively. Talaraculones A
      and B (1 and 2) exhibited stronger inhibitory activity against alpha-glucosidase
      than the positive control acarbose (IC50 = 101.5 MUM), with IC50 values of 78.6
      and 22.9 MUM, respectively.

PMID- 28749672
TI  - Visible Light Production of Hydrogen by Ablated Graphene: Water Splitting or
      Carbon Gasification?
AB  - Reduced graphene oxide modified by pulsed laser ablation causes water splitting
      under visible light illumination (532 nm). When the light source is a pulsed
      laser, water splitting is accompanied by carbon gasification (CO formation);
      however, conventional (LED) light sources produce water splitting exclusively.

PMID- 28749671
TI  - Antifungal and Cytotoxic beta-Resorcylic Acid Lactones from a Paecilomyces
      Species.
AB  - Eight new beta-resorcylic acid lactones (RALs), including the hypothemycin-type
      compounds paecilomycins N-P (1-3) and the radicicol-type metabolites
      dechloropochonin I (4), monocillins VI (5) and VII (6), 4'-hydroxymonocillin IV
      (7), and 4'-methoxymonocillin IV (8), along with nine known RALs (9-17), were
      isolated from the cultures of Paecilomyces sp. SC0924. Compounds 1 and 2 feature
      a novel 6/11/5 ring system, and 3 is the first 5'-keto RAL. The structures of 1-8
      were elucidated on the basis of extensive spectroscopic analysis, X-ray
      diffraction analysis, and theoretical calculations of ECD spectra. Compounds 3,
      5, and 6 exhibit cytotoxicity against MCF-7, A549, and HeLa cells, and compounds
      5 and 7 display antifungal activity against Peronophythora litchii.

PMID- 28749674
TI  - Reaction Ensemble Monte Carlo Simulation of Xylene Isomerization in Bulk Phases
      and under Confinement.
AB  - The original reaction move for the reaction ensemble Monte Carlo (RxMC) method is
      adapted to align both the position and orientation of inserted product molecules
      and deleted reactant molecules. The accuracy and efficiency of this move is
      demonstrated for xylene isomerization in vapor, liquid, and supercritical phases.
      Classical RxMC requires the ideal gas free energy of reaction DeltaGrxnideal as
      an input. We compare three methods for computing DeltaGrxnideal: using tabulated
      enthalpies and entropies of formation, using the harmonic oscillator and rigid
      rotor approximations and using QM/MM alchemical transformation combined with
      multistate Bennett acceptance ratio. We find that the tabulated free energies of
      reaction give the best agreement with experimental equilibrium compositions in
      bulk fluids. RxMC simulations in a carbon nanotube with an inner diameter of
      approximately 6 A show that p-xylene becomes the dominant isomer under
      confinement, an effect consistent with the production of p-xylene in the zeolite
      ZSM-5. We also show that o-xylene becomes the dominant isomer in nanotubes with
      an inner diameter of 7-8 A. We find that both m- and p-xylene exhibit a loss of
      rotational entropy in nanotubes of this diameter, effectively allowing o-xylene
      to fit into cavities inaccessible to the other isomers.

PMID- 28749673
TI  - A Nonheme, High-Spin {FeNO}8 Complex that Spontaneously Generates N2O.
AB  - One-electron reduction of [Fe(NO)-(N3PyS)]BF4 (1) leads to the production of the
      metastable nonheme {FeNO}8 complex, [Fe(NO)(N3PyS)] (3). Complex 3 is a rare
      example of a high-spin (S = 1) {FeNO}8 and is the first example, to our
      knowledge, of a mononuclear nonheme {FeNO}8 species that generates N2O. A second,
      novel route to 3 involves addition of Piloty's acid, an HNO donor, to an FeII
      precursor. This work provides possible new insights regarding the mechanism of
      nitric oxide reductases.

PMID- 28749675
TI  - Differential Interaction of Synthetic Glycolipids with Biomimetic Plasma Membrane
      Lipids Correlates with the Plant Biological Response.
AB  - Natural and synthetic amphiphilic molecules including lipopeptides,
      lipopolysaccharides, and glycolipids are able to induce defense mechanisms in
      plants. In the present work, the perception of two synthetic C14 rhamnolipids,
      namely, Alk-RL and Ac-RL, differing only at the level of the lipid tail terminal
      group have been investigated using biological and biophysical approaches. We
      showed that Alk-RL induces a stronger early signaling response in tobacco cell
      suspensions than does Ac-RL. The interactions of both synthetic RLs with
      simplified biomimetic membranes were further analyzed using experimental and in
      silico approaches. Our results indicate that the interactions of Alk-RL and Ac-RL
      with lipids were different in terms of insertion and molecular responses and were
      dependent on the lipid composition of model membranes. A more favorable insertion
      of Alk-RL than Ac-RL into lipid membranes is observed. Alk-RL forms more stable
      molecular assemblies than Ac-RL with phospholipids and sterols. At the molecular
      level, the presence of sterols tends to increase the RLs' interaction with lipid
      bilayers, with a fluidizing effect on the alkyl chains. Taken together, our
      findings suggest that the perception of these synthetic RLs at the membrane level
      could be related to a lipid-driven process depending on the organization of the
      membrane and the orientation of the RLs within the membrane and is correlated
      with the induction of early signaling responses in tobacco cells.

PMID- 28749676
TI  - Organocatalytic Enantioselective Vinylogous Michael-Aldol Cascade for the
      Synthesis of Spirocyclic Compounds.
AB  - Enantioselective synthesis of pyrazolone-fused spirocyclohexenols by the
      secondary amine-catalyzed cascade reaction of alpha,beta-unsaturated aldehydes
      with alpha-arylidene pyrazolinones is reported. This formal [3 + 3] organocascade
      reaction proceeds through a vinylogous Michael-aldol sequence to furnish the
      spiroheterocycles with three stereocenters including an all-carbon quaternary
      center in good yields and selectivities. The catalytic generation of alpha,beta
      unsaturated iminium ions from enals and tandem dienolate/enolate formation from
      pyrazolinones are the key for the success of this spiroannulation reaction.

PMID- 28749677
TI  - Nature-Inspired Construction of Two-Dimensionally Self-Assembled Peptide on
      Pristine Graphene.
AB  - Peptide assemblies have received significant attention because of their important
      role in biology and applications in bionanotechnology. Despite recent efforts to
      elucidate the principles of peptide self-assembly for developing novel functional
      devices, peptide self-assembly on two-dimensional nanomaterials has remained
      challenging. Here, we report nature-inspired two-dimensional peptide self
      assembly on pristine graphene via optimization of peptide-peptide and peptide
      graphene interactions. Two-dimensional peptide self-assembly was designed based
      on statistical analyses of >104 protein structures existing in nature and
      atomistic simulation-based structure predictions. We characterized the structures
      and surface properties of the self-assembled peptide formed on pristine graphene.
      Our study provides insights into the formation of peptide assemblies coupled with
      two-dimensional nanomaterials for further development of nanobiocomposite
      devices.

PMID- 28749678
TI  - Photofluidic Near-Field Mapping of Electric-Field Resonance in Plasmonic
      Metasurface Assembled with Gold Nanoparticles.
AB  - We present a near-field mapping of electric fields from the individual
      superspherical and ultrasmooth gold nanoparticles (AuNPs) and artificially
      assembled AuNP nanostructures by measuring the reconfiguration of an azobenzene
      containing polymer(azo-polymer) film. Various configurations of AuNPs and the azo
      polymer were studied with atomic force microscopy measurements and calculations.
      The interference was systematically studied with AuNP dimers of various gap
      distances and different embedding depth in the polymer film. Finally, we
      successfully demonstrated the interference of standing waves in artificially
      assembled plasmonic metasurface.

PMID- 28749679
TI  - Atomic-Level Design of Water-Resistant Hybrid Perovskites for Solar Cells by
      Using Cluster Ions.
AB  - Organic-inorganic hybrid perovskites have emerged as the most promising material
      in the development of next-generation solar cells. However, the stability of
      these materials exemplified by CH3NH3PbI3 is the most pressing challenge; it
      readily decomposes when exposed to moisture. Here, we show how one can use a
      particular type of cluster ions, known as pseudohalides, to enhance the water
      resistance of the hybrid perovskite, while maintaining its favorable electronic
      properties. Starting with a simple physical model, we propose a new class of
      water-resistant hybrid perovskites as solar-cell absorbers based on the cluster
      ions by using DFT calculations and ab initio molecular dynamics. Limitations of
      applying the currently known pseudohalides for our purpose are also discussed.

PMID- 28749680
TI  - Structure of the Clean and Oxygen-Covered Cu(100) Surface at Room Temperature in
      the Presence of Methanol Vapor in the 10-200 mTorr Pressure Range.
AB  - Using ambient pressure X-ray photoelectron spectroscopy (APXPS) and high pressure
      scanning tunneling microscopy (HPSTM), we show that in equilibrium with 0.01-0.2
      Torr of methanol vapor, at room temperature, the Cu(100) surface is covered with
      methoxy species forming a c(2 * 2) overlayer structure. In contrast, no methoxy
      is formed if the surface is saturated with an ordered oxygen layer, even when the
      methanol pressure is 0.2 Torr. At oxygen coverages below saturation, methanol
      dissociates and reacts with the atomic oxygen, producing methoxy and formate on
      the surface, and formaldehyde that desorbs to the gas phase. Unlike the case of
      pure carbon monoxide and carbon dioxide, methanol does not induce the
      restructuring of the Cu(100) surface. These results provide insight into
      catalytic anhydrous production of aldehydes.

PMID- 28749681
TI  - Electron-Transfer-Mediated Uranium Detection Using Quasi-Type II Core-Shell
      Quantum Dots: Insight into Mechanistic Pathways.
AB  - Uranium is one of the most toxic and important elements present in the
      environment, and because of its high toxicity, ultra-trace-level detection is of
      utmost importance. Many methods were reported earlier for this purpose, but each
      has its own limitations such as high cost, sophisticated instrumentation, sample
      processing, and so forth. Herein we have demonstrated an alternate method that is
      much simpler and can be used for the ultra-trace-level detection of uranium. We
      have synthesized 3-mercaptopropionic acid (MPA)-capped CdSe/CdS core-shell
      quantum dots (CSQDs) and used its photoluminescence properties to detect uranium
      in solution. Steady-state emission studies suggest the luminescence quenching of
      CSQDs in the presence of uranium. Redox levels of CSQDs and uranium suggests that
      the electron-transfer process from photoexcited CSQDs to uranium is a
      thermodynamically viable process, which has subsequently been confirmed by time
      resolved studies. A Stern-Volmer plot of CSQDs with uranium suggests that the
      detection limit of this method is 74.5 ppb. The method has an advantage over
      other reported methods for being simple and low cost and requiring a small amout
      of sample processing. To the best of our knowledge, we are reporting for the
      first time uranium detection using quasi-type II CSQDs and proposing the
      mechanistic path through luminescence spectroscopy, which in turn helps us to
      design an efficient detection method.

PMID- 28749682
TI  - Nickel-Catalyzed Coupling of Azoles with Aromatic Nitriles.
AB  - This manuscript describes the Ni-catalyzed coupling of azoles with aromatic
      nitriles. The use of BPh3 promotes these arylations with electronically diverse
      azoles and benzonitriles. While the nickel catalyst is necessary for the
      arylations of phenyl oxazoles, arylation of benzoxazoles with some nitriles
      affords the arylated products even in the absence of the Ni catalyst albeit in
      lower yield than the catalyzed process. The Ni-catalyzed process exhibits higher
      rates and a broader scope than the uncatalyzed transformation.

PMID- 28749683
TI  - Control of Surface-Localized, Enzyme-Assisted Self-Assembly of Peptides through
      Catalyzed Oligomerization.
AB  - Localized self-assembly allowing both spatial and temporal control over the
      assembly process is essential in many biological systems. This can be achieved
      through localized enzyme-assisted self-assembly (LEASA), also called enzyme
      instructed self-assembly, where enzymes present on a substrate catalyze a
      reaction that transforms noninteracting species into self-assembling ones. Very
      few LEASA systems have been reported so far, and the control of the self-assembly
      process through the surface properties represents one essential step toward their
      use, for example, in artificial cell mimicry. Here, we describe a new type of
      LEASA system based on alpha-chymotrypsin adsorbed on a surface, which catalyzes
      the production of (KL)nOEt oligopeptides from a KLOEt (K: lysine; L: leucine; OEt
      ethyl ester) solution. When a critical concentration of the formed oligopeptides
      is reached near the surface, they self-assemble into beta-sheets resulting in a
      fibrillar network localized at the interface that can extend over several
      micrometers. One significant feature of this process is the existence of a lag
      time before the self-assembly process starts. We investigate, in particular, the
      effect of the alpha-chymotrypsin surface density and KLOEt concentration on the
      self-assembly kinetics. We find that the lag time can be finely tuned through the
      surface density in alpha-chymotrypsin and KLOEt concentration. For a given
      surface enzyme concentration, a critical KLOEt concentration exists below which
      no self-assembly takes place. This concentration increases when the surface
      density in enzyme decreases.

PMID- 28749684
TI  - Mechanistic Insight into Cypridina Bioluminescence with a Combined Experimental
      and Theoretical Chemiluminescent Approach.
AB  - The bioluminescent reaction of the "sea firefly" Cypridina hilgendorfii is a
      prototypical system for marine bioluminescence, as its substrate possesses an
      imidazopyrazinone core that is a common link among organisms of eight phyla. The
      elucidation of the mechanism behind Cypridina bioluminescence is essential for
      future applications in bioimaging, biomedicine, and bioanalysis. In this study we
      have investigated the key step of chemiexcitation with a combined experimental
      and theoretical approach. The obtained results indicate that neutral dioxetanone
      is responsible for efficient chemiexcitation, as the thermolysis of this species
      gives access to a long region of the potential energy surface (PES), where the
      ground and excited singlet states are degenerated. Contrary to expected, neither
      chemically induced electron-exchange luminescence (CIEEL) nor charge transfer
      initiated luminescence (CTIL) can be used to explain imidazopyrazinone-based
      bioluminescence, as there is no clear relationship between electron (ET)/charge
      (CT) transfer (occurring between the electron-rich moiety and dioxetanone) and
      chemiexcitation. Attractive electrostatic interactions between the CO2 and
      oxyluciferin moieties allow neutral dioxetanone to spend time in the PES region
      of degeneracy, while repulsive interactions for anionic dioxetanone lead to a
      quicker CO2 detachment.

PMID- 28749685
TI  - High-Throughput Label- and Immobilization-Free Screening of Human Milk
      Oligosaccharides Against Lectins.
AB  - The intense interest in the mechanisms responsible for the beneficial effects of
      breast-feeding on infant health has created a significant need for analytical
      methods capable of rapidly identifying interactions between human milk
      oligosaccharides (HMOs) and their protein receptors. Currently, there are no
      established, high-throughput assays for the screening libraries of free
      (unmodified) HMOs against lectins. The present work describes a rapid and label-
      and immobilization-free assay, based on catch-and-release electrospray ionization
      mass spectrometry (CaR-ESI-MS), capable of simultaneously screening mixtures of
      free HMOs of known concentration for binding to lectins in vitro. Ligand
      identification relies on the molecular weights (MWs), ion mobility separation
      arrival times, and collision-induced dissociation fingerprints of HMO anions
      released from the target protein in the gas phase. To establish the reliability
      of the assay, a library of 31 free HMOs, ranging in size from tri- to
      octasaccharide, was screened against three human galectin (hGal) proteins (a
      stable mutant of hGal1 (hGal-1), a C-terminal fragment of hGal-3 (hGal-3C) and
      hGal-7), with known HMO affinities. When implemented using an equimolar
      concentration library, the CaR-ESI-MS assay identified 100% of ligands with
      affinities >500 M-1 and >=93% of all HMO ligands (hGal-1-31 of 31 ligands; hGal
      3C-25 of 25; hGal-7-28 of 30); no false positives were detected. The assay also
      successfully identified the majority of the highest affinity HMO ligands (or
      isomer sets that contain the highest affinity ligands) in the library for each of
      the three hGal. Notably, for each lectin, CaR-ESI-MS screening required <1 h to
      complete and consumed <5 ng of each HMO and <0.5 MUg of protein.

PMID- 28749686
TI  - Metallic Vanadium Disulfide Nanosheets as a Platform Material for Multifunctional
      Electrode Applications.
AB  - Nanothick metallic transition metal dichalcogenides such as VS2 are essential
      building blocks for constructing next-generation electronic and energy-storage
      applications, as well as for exploring unique physical issues associated with the
      dimensionality effect. However, such two-dimensional (2D) layered materials have
      yet to be achieved through either mechanical exfoliation or bottom-up synthesis.
      Herein, we report a facile chemical vapor deposition route for direct production
      of crystalline VS2 nanosheets with sub-10 nm thicknesses and domain sizes of tens
      of micrometers. The obtained nanosheets feature spontaneous superlattice
      periodicities and excellent electrical conductivities (~3 * 103 S cm-1), which
      has enabled a variety of applications such as contact electrodes for monolayer
      MoS2 with contact resistances of ~1/4 to that of Ni/Au metals, and as
      supercapacitor electrodes in aqueous electrolytes showing specific capacitances
      as high as 8.6 * 102 F g-1. This work provides fresh insights into the delicate
      structure-property relationship and the broad application prospects of such
      metallic 2D materials.

PMID- 28749687
TI  - Site-Specific Covalent Conjugation of Modified mRNA by tRNA Guanine
      Transglycosylase.
AB  - Modified mRNA (mod-mRNA) has recently been widely studied as the form of RNA
      useful for therapeutic applications due to its high stability and lowered immune
      response. Herein, we extend the scope of the recently established RNA-TAG
      (transglycosylation at guanosine) methodology, a novel approach for genetically
      encoded site-specific labeling of large mRNA transcripts, by employing mod-mRNA
      as substrate. As a proof of concept, we covalently attached a fluorescent probe
      to mCherry encoding mod-mRNA transcripts bearing 5-methylcytidine and/or
      pseudouridine substitutions with high labeling efficiencies. To provide a
      versatile labeling methodology with a wide range of possible applications, we
      employed a two-step strategy for functionalization of the mod-mRNA to highlight
      the therapeutic potential of this new methodology. We envision that this novel
      and facile labeling methodology of mod-RNA will have great potential in
      decorating both coding and noncoding therapeutic RNAs with a variety of
      diagnostic and functional moieties.

PMID- 28749688
TI  - Structural and Dynamic "Portraits" of Recombinant and Native Cytotoxin I from
      Naja oxiana: How Close Are They?
AB  - Today, recombinant proteins are quite widely used in biomedical and
      biotechnological applications. At the same time, the question about their full
      equivalence to the native analogues remains unanswered. To gain additional
      insight into this problem, intimate atomistic details of a relatively simple
      protein, small and structurally rigid recombinant cardiotoxin I (CTI) from cobra
      Naja oxiana venom, were characterized using nuclear magnetic resonance (NMR)
      spectroscopy and atomistic molecular dynamics (MD) simulations in water. Compared
      to the natural protein, it contains an additional Met residue at the N-terminus.
      In this work, the NMR-derived spatial structure of uniformly 13C- and 15N-labeled
      CTI and its dynamic behavior were investigated and subjected to comparative
      analysis with the corresponding data for the native toxin. The differences were
      found in dihedral angles of only a single residue, adjacent to the N-terminal
      methionine. Microsecond-long MD traces of the toxins reveal an increased
      flexibility in the residues spatially close to the N-Met. As the detected
      structural and dynamic changes of the two CTI models do not result in substantial
      differences in their cytotoxicities, we assume that the recombinant protein can
      be used for many purposes as a reasonable surrogate of the native one. In
      addition, we discuss general features of the spatial organization of cytotoxins,
      implied by the results of the current combined NMR and MD study.

PMID- 28749689
TI  - Superacidic Cyclization of Activated Anthranilonitriles into 2-Unsubstituted-4
      aminoquinolines.
AB  - 4-Aminoquinolines were prepared in a three-step synthesis starting from
      substituted anthranilonitriles. The condensation on 1,1,1-trichloro-4-ethoxybut-3
      enone proceeded efficiently either neat or in refluxing EtOH. Cyclization in
      superacidic trifluoromethanesulfonic acid provided unstable intermediate, which
      upon treatment with NaOEt in ethanol, afforded the expected esters. Theoretical
      investigations pointed out a monoprotonated nitrilium as the reactive species
      during the cyclization process.

PMID- 28749690
TI  - Multiscale Molecular Dynamics Simulations of Polaritonic Chemistry.
AB  - When photoactive molecules interact strongly with confined light modes as found
      in plasmonic structures or optical cavities, new hybrid light-matter states can
      form, the so-called polaritons. These polaritons are coherent superpositions (in
      the quantum mechanical sense) of excitations of the molecules and of the cavity
      photon or surface plasmon. Recent experimental and theoretical works suggest that
      access to these polaritons in cavities could provide a totally new and attractive
      paradigm for controlling chemical reactions that falls in between traditional
      chemical catalysis and coherent laser control. However, designing cavity
      parameters to control chemistry requires a theoretical model with which the
      effect of the light-matter coupling on the molecular dynamics can be predicted
      accurately. Here we present a multiscale quantum mechanics/molecular mechanics
      (QM/MM) molecular dynamics simulation model for photoactive molecules that are
      strongly coupled to confined light in optical cavities or surface plasmons. Using
      this model we have performed simulations with up to 1600 Rhodamine molecules in a
      cavity. The results of these simulations reveal that the contributions of the
      molecules to the polariton are time-dependent due to thermal fluctuations that
      break symmetry. Furthermore, the simulations suggest that in addition to the
      cavity quality factor, also the Stokes shift and number of molecules control the
      lifetime of the polariton. Because large numbers of molecules interacting with
      confined light can now be simulated in atomic detail, we anticipate that our
      method will lead to a better understanding of the effects of strong coupling on
      chemical reactivity. Ultimately the method may even be used to systematically
      design cavities to control photochemistry.

PMID- 28749691
TI  - Nonacidic Farnesoid X Receptor Modulators.
AB  - As a cellular bile acid sensor, farnesoid X receptor (FXR) participates in
      regulation of bile acid, lipid and glucose homeostasis, and liver protection.
      Clinical results have validated FXR as therapeutic target in hepatic and
      metabolic diseases. To date, potent FXR agonists share a negatively ionizable
      function that might compromise their pharmacokinetic distribution and behavior.
      Here we report the development and characterization of a high-affinity FXR
      modulator not comprising an acidic residue.

PMID- 28749692
TI  - Pickering Emulsions Stabilized by pH-Responsive Microgels and Their Scalable
      Transformation to Robust Submicrometer Colloidoisomes with Selective
      Permeability.
AB  - Colloidosomes are micrometer-sized hollow particles that have shells consisting
      of coagulated or fused colloid particles. While many large colloidosomes with
      sizes well above 1.0 MUm have been prepared, there are fewer examples of
      submicrometer colloidosomes. Here, we establish a simple emulsion templating
      based method for the preparation of robust submicrometer pH-responsive microgel
      colloidosomes. The colloidosomes are constructed from microgel particles based on
      ethyl acrylate and methacrylic acid with peripheral vinyl groups. The pH
      responsive microgels acted as both a Pickering emulsion stabilizer and macro
      cross-linker. The emulsion formation studies showed that the minimum droplet
      diameter was reached when the microgel particles were partially swollen. Microgel
      colloidosomes were prepared by covalently interlinking the microgels adsorbed at
      the oil-water interface using thermal free-radical coupling. The colloidosomes
      were prepared using a standard high-shear mixer with two different rotor sizes
      that corresponded to high shear (HS) and very high shear (VHS) mixing conditions.
      The latter enabled the construction of submicrometer pH-responsive microgel
      colloidosomes on the gram scale. The colloidosomes swelled strongly when the pH
      increased to above 6.0. The colloidosomes were robust and showed no evidence of
      colloidosome breakup at high pH. The effect of solute size on shell permeation
      was studied using a range of FITC-dextran polymers, and size-selective permeation
      occurred. The average pore size of the VHS microgel-colloidosomes was estimated
      to be between 6.6 and 9.0 nm at pH 6.2. The microgel-colloidosome properties
      suggest that they have the potential for future applications in cosmetics,
      photonics, and delivery.

PMID- 28749693
TI  - Experimental and Computational Development of a Conformationally Flexible
      Template for the meta-C-H Functionalization of Benzoic Acids.
AB  - A conformationally flexible template for the meta-C-H olefination of benzoic
      acids was designed through both experimental and computational efforts. The newly
      designed template favors a silver-palladium heterodimer low barrier transition
      state, and demonstrates that it is feasible to lengthen templates so as to
      achieve meta-selectivity when the distance between the functional handle of the
      native substrate and target C-H bond decreases. Analysis of the ortho-, meta-,
      and para-C-H cleavage transition states determined that the new template
      conformation optimizes the interaction between the nitrile and palladium-silver
      dimer in the meta-transition state, enabling palladium to cleave meta-C-H bonds
      with moderate-to-good yields and generally high regioselectivity.
      Regioselectivity is governed exclusively by the template, and kinetic experiments
      reveal that there is a 4-fold increase in rate in the presence of monoprotected
      amino acid ligands. Using a Boltzmann distribution of all accessible C-H
      activation transition states, it is possible to computationally predict meta
      selectivity in a number of investigated templates with reasonable accuracy.
      Structural and distortion energies reported may be used for the further
      development of templates for meta-C-H activation of hitherto unexplored arene
      substrates.

PMID- 28749694
TI  - How Do Methyl Groups Enhance the Triplet Chemiexcitation Yield of Dioxetane?
AB  - Chemiluminescence is the emission of light as a result of a nonadiabatic chemical
      reaction. The present work is concerned with understanding the yield of
      chemiluminescence, in particular how it dramatically increases upon methylation
      of 1,2-dioxetane. Both ground-state and nonadiabatic dynamics (including singlet
      excited states) of the decomposition reaction of various methyl-substituted
      dioxetanes have been simulated. Methyl-substitution leads to a significant
      increase in the dissociation time scale. The rotation around the O-C-C-O dihedral
      angle is slowed; thus, the molecular system stays longer in the "entropic trap"
      region. A simple kinetic model is proposed to explain how this leads to a higher
      chemiluminescence yield. These results have important implications for the design
      of efficient chemiluminescent systems in medical, environmental, and industrial
      applications.

PMID- 28749695
TI  - In Situ Growth of Clean Pd Nanoparticles on Polystyrene Microspheres Assisted by
      Functional Reduced Graphene Oxide and Their Excellent Catalytic Properties.
AB  - Herein an in situ growth of clean palladium nanoparticles (Pd NPs) on functional
      reduced graphene oxide (RGO)-coated polystyrene (PS) microspheres is achieved by
      a simple two-step process. On the basis of the hydrophobic interaction and pi
      electron interaction, the PS/RGO composite particles are first prepared by the
      reduction of graphene oxide in the presence of PS microspheres. Second, without
      using any additional reducing agent or stabilizer, the clean Pd NPs grow in situ
      on the surface of PS/RGO composite particles in water through a spontaneous redox
      reaction between Pd2+ and RGO. Significantly, owing to the stabilizer-free
      surface of Pd NPs and the synergistic effect of RGO and Pd NPs, the resultant
      PS/RGO@Pd composite particles feature pronounced catalytic activity toward the
      reduction of p-nitrophenol and Suzuki coupling reactions. Moreover, the catalyst
      particles can be easily recovered by centrifugation because of the large size of
      support microspheres and recycled consecutively.

PMID- 28749696
TI  - Influence of Physiological Gastrointestinal Surfactant Ratio on the Equilibrium
      Solubility of BCS Class II Drugs Investigated Using a Four Component Mixture
      Design.
AB  - The absorption of poorly water-soluble drugs is influenced by the luminal
      gastrointestinal fluid content and composition, which control solubility.
      Simulated intestinal fluids have been introduced into dissolution testing
      including endogenous amphiphiles and digested lipids at physiological levels;
      however, in vivo individual variation exists in the concentrations of these
      components, which will alter drug absorption through an effect on solubility. The
      use of a factorial design of experiment and varying media by introducing
      different levels of bile, lecithin, and digested lipids has been previously
      reported, but here we investigate the solubility variation of poorly soluble
      drugs through more complex biorelevant amphiphile interactions. A four-component
      mixture design was conducted to understand the solubilization capacity and
      interactions of bile salt, lecithin, oleate, and monoglyceride with a constant
      total concentration (11.7 mM) but varying molar ratios. The equilibrium
      solubility of seven low solubility acidic (zafirlukast), basic (aprepitant,
      carvedilol), and neutral (fenofibrate, felodipine, griseofulvin, and
      spironolactone) drugs was investigated. Solubility results are comparable with
      literature values and also our own previously published design of experiment
      studies. Results indicate that solubilization is not a sum accumulation of
      individual amphiphile concentrations, but a drug specific effect through
      interactions of mixed amphiphile compositions with the drug. This is probably due
      to a combined interaction of drug characteristics; for example, lipophilicity,
      molecular shape, and ionization with amphiphile components, which can generate
      specific drug-micelle affinities. The proportion of each component can have a
      remarkable influence on solubility with, in some cases, the highest and lowest
      points close to each other. A single-point solubility measurement in a fixed
      composition simulated media or human intestinal fluid sample will therefore
      provide a value without knowledge of the surrounding solubility topography
      meaning that variability may be overlooked. This study has demonstrated how the
      amphiphile ratios influence drug solubility and highlights the importance of the
      envelope of physiological variation when simulating in vivo drug behavior.

PMID- 28749697
TI  - TLD measurements and Monte Carlo calculations of head and neck organ and
      effective doses for cone beam computed tomography using 3D Accuitomo 170.
AB  - OBJECTIVES: In dentistry, the use of cone beam CT has steadily increased over the
      last few years. The aim of this study was to measure organ doses and to perform
      dose calculations based on Monte Carlo (MC) simulations to work out a basis for
      full three-dimensional (3D) dose calculations for any patient examination
      performed with the machine used in this study. METHODS: TLD-100 LiF detectors
      were placed at 71 measurement positions on the surface and within a RT-Humanoid
      phantom to cover all relevant radiosensitive organs and tissues. Three
      examinations with different protocols were performed with the 3D Accuitomo(r) and
      dose calculations with MC simulations were carried out for the same three
      protocols using the EGSnrc MC transport code system. RESULTS: Field of views of
      140 * 100, 80 * 50 and 40 * 40 mm2 were selected, the mean organ doses were
      measured as 5.2, 2.75 and 1.5 mGy and the effective doses were determined as 250,
      97 and 48 uSv. For the MC simulation of organ doses and the thermoluminescent
      dosemeter measurements, an overall agreement within +/-10.1% (two standard
      deviations) was achieved. The measured dose values for 3D Accuitomo(r) were about
      a factor 2 lower when compared with conventional CT examinations. CONCLUSIONS:
      Reliable results for the organ doses as well as effective dose values were
      achieved with thermoluminescent dosemeter measurements in the RT-Humanoid
      phantom. This study provides the basis for the application of MC simulations for
      further dose determinations of cone beam CT machines. The MC calculation may
      therefore be a valuable tool to support the dentists in the evaluation of the
      trade-off between additional information that may be relevant to the choice of
      therapy and the additional dose given to the patient.

PMID- 28749698
TI  - The safety and efficacy of the 5-HT 1F receptor agonist lasmiditan in the acute
      treatment of migraine.
AB  - INTRODUCTION: Migraine is among the most disabling disorders worldwide, with a
      significant therapeutic need. Triptans are drugs of choice in the acute attack
      treatment, but they are contraindicated in patients with vascular conditions due
      to their potential vasoconstrictive properties. Further limitations include side
      effects, inconsistency in therapeutic action and possible non-response.
      Lasmiditan, a highly selective 5-HT1F receptor agonist, is a novel acute anti
      migraine substance devoid of vasoconstriction. Areas covered: This article
      reviews the clinical efficacy and safety of oral and intravenous lasmiditan as a
      possible acute migraine treatment. We analyze all currently available results in
      Phase I to III studies. Expert opinion: Lasmiditan is a promising acute migraine
      therapy, in particular for patients at cardiovascular risk. Phase II and the
      first Phase III clinical trials show a significant better headache response in
      comparison to placebo. The efficacy of lasmiditan proves that vasoconstriction is
      not essential for acute migraine therapy and thereby points, in addition to a
      well-established trigeminal contribution, to central neuronal mechanisms in
      migraine pathophysiology. Lasmiditan penetrates the blood-brain barrier and CNS
      associated adverse events are common, but mostly in mild to moderate severity.
      The results of long-term Phase III studies will determine if these adverse events
      represent a limitation in clinical practice.

PMID- 28749699
TI  - Patellofemoral Joint Loads During Running at the Time of Return to Sport in Elite
      Athletes With ACL Reconstruction.
AB  - BACKGROUND: Patellofemoral joint pain and degeneration are common in patients who
      undergo anterior cruciate ligament reconstruction (ACLR). The presence of
      patellofemoral joint pain significantly affects the patient's ability to continue
      sport participation and may even affect participation in activities of daily
      living. The mechanisms behind patellofemoral joint pain and degeneration are
      unclear, but previous research has identified altered patellofemoral joint
      loading in individuals with patellofemoral joint pain when running. It is unclear
      whether this process occurs after ACLR. PURPOSE: To assess the patellofemoral
      joint stresses during running in ACLR knees and compare the findings to the
      noninjured knee and matched control knees. STUDY DESIGN: Controlled laboratory
      study. METHODS: Thirty-four elite sports practitioners who had undergone ACLR and
      34 age- and sex-matched controls participated in the study. The participants'
      running gait was assessed via 3D motion capture, and knee loads and forces were
      calculated by use of inverse dynamics. RESULTS: A significance difference was
      found in knee extensor moment, knee flexion angles, patellofemoral contact force
      (about 23% greater), and patellofemoral contact pressure (about 27% greater)
      between the ACLR and the noninjured limb ( P <= .04) and between the ACLR and the
      control limb ( P <= .04); no significant differences were found between the
      noninjured and control limbs ( P >= .44). CONCLUSION: Significantly greater
      levels of patellofemoral joint stress and load were found in the ACLR knee
      compared with the noninjured and control knees. CLINICAL RELEVANCE: Altered
      levels of patellofemoral stress in the ACLR knee during running may predispose
      individuals to patellofemoral joint pain.

PMID- 28749700
TI  - Radiographic diagnosis of root fractures: a systematic review, meta-analyses and
      sources of heterogeneity.
AB  - OBJECTIVES: Many studies to evaluate the accuracy of root fracture diagnosis have
      been conducted. However, there is a scarcity of studies to assess the quality and
      the sources of heterogeneity in the literature. For this reason, the aim of this
      study was to conduct systematic reviews and meta-analyses to summarize the
      available evidence on detection of root fractures by cone beam CT (CBCT) and
      periapical radiograph (PR) images and the interference of artefact by
      investigating possible sources of heterogeneity. METHODS: Studies reporting root
      fracture detection, from January 2010 to February 2016, were selected. All
      selected studies were subjected to selection criteria and then, comparative and
      qualitative analyses by using the quality assessment of diagnostic accuracy
      studies (QUADAS-2) tool were performed. Pooled sensitivity, specificity and
      diagnostic odds ratios were calculated. Also, receiver operator characteristics
      (ROC) curves were built to summarize the results. SROC curve analyses were
      performed to investigate the heterogeneity among studies. RESULTS: Initially, 799
      articles were selected. After screening titles and abstracts, 743 articles were
      excluded. After reading the remaining 56 full-texts, 47 relevant articles were
      included in this study. Diagnostic odds ratio values revealed a wide range of
      results across the studies and determined a higher heterogeneity for PR compared
      with CBCT. The analyses of the SROC curves compared CBCT imaging versus PR in the
      diagnosis of root fracture, favouring CBCT modality. CONCLUSIONS: CBCT was the
      imaging exam that rendered a higher diagnostic accuracy for root fractures.

PMID- 28749701
TI  - Fish scale artefact on an intraoral imaging receptor.
AB  - OBJECTIVES: To describe an artefact, termed the fish scale artefact, present on
      an intraoral imaging receptor. METHODS: Thirty brand new DIGORA Optime
      photostimulable phosphor (PSP) plates (Soredex/Orion Corp., Helsinki, Finland)
      were imaged using the dental digital quality assurance radiographic phantom
      (Dental Imaging Consultants LLC, San Antonio, TX). All PSP plates were scanned at
      the same spatial resolution (dpi) using the high resolution mode. Two evaluators
      assessed all 30 plates. Each evaluator assessed the 30 PSP plates separately for
      purposes of establishing interrater reliability, and then together in order to
      obtain the gold standard result. RESULTS: The fish scale artefact was detected on
      46.7% of the PSP plates. The kappa coefficient for interrater reliability was
      0.86 [95% CI (0.69-1.00)], indicating excellent interrater reliability. For
      Evaluator 1, sensitivity was 0.85 [95% CI (0.55-0.98)]; specificity was 0.94 [CI
      (0.71-1.00)] and overall accuracy was 0.90 [95% CI (0.73-0.98)]. For Evaluator 2,
      sensitivity was 1.00 [95% CI (0.75-1.00)]; specificity was 0.94 [CI (0.71-1.00)]
      and overall accuracy was 0.97 [95% CI (0.83-1.00)]. These results indicate
      excellent agreement with the gold standard for both evaluators. CONCLUSIONS:
      Utilizing a comprehensive quality assurance protocol, we identified a fish scale
      artefact inherent to the image receptor. Additional research is needed to
      determine if the artefact remains static over time or if it increases over time.
      Likewise, research to determine the potential sources contributing to an increase
      in the artefact is needed.

PMID- 28749702
TI  - What Patients and Providers Want to Know About Complementary and Integrative
      Health Therapies.
AB  - OBJECTIVES: We conducted a quality improvement project to determine (1) what
      information providers and patients most wanted to learn about complementary and
      integrative health (CIH) therapies and (2) in what format they wanted to receive
      this information. The overall aim was to develop educational materials to
      facilitate the CIH therapy decision-making processes. DESIGN: We used mixed
      methods to iteratively pilot test and revise provider and patient educational
      materials on yoga and meditation. We conducted semistructured interviews with 11
      medical providers and held seven focus groups and used feedback forms with 52
      outpatients. We iteratively developed and tested three versions of both provider
      and patient materials. Activities were conducted at four Veterans Administration
      medical facilities (two large medical centers and two outpatient clinics).
      RESULTS: Patients want educational materials with clearly stated basic
      information about: (1) what mindfulness and yoga are, (2) what a yoga/meditation
      class entails and how classes can be modified to suit different abilities, (3)
      key benefits to health and wellness, and (4) how to find classes at the
      hospital/clinic. Diverse media (videos, handouts, pocket guides) appealed to
      different Veterans. Videos should depict patients speaking to patients and
      demonstrating the CIH therapy. Written materials should be one to three pages
      with colors, and images and messages targeting a variety of patients. Providers
      wanted a concise (one-page) sheet in black and white font with no images listing
      the scientific evidence for CIH therapies from high-impact journals, organized by
      either type of CIH or health condition to use during patient encounters, and
      including practical information about how to refer patients. CONCLUSIONS:
      Providers and patients want to learn more about CIH therapies, but want the
      information in succinct, targeted formats. The information learned and materials
      developed in this study can be used by others to educate patients and providers
      on CIH therapies.

PMID- 28749703
TI  - A new simple three-dimensional method to characterize upper airway in
      orthognathic surgery patient.
AB  - OBJECTIVES: To develop and validate a new reproducible 3D upper airway analysis
      based on skeletal structures not involved in the modification, which occur during
      orthognathic surgery. METHODS: From retrospective cohort of orthognathic
      surgically treated patients, pre- and postsurgical CBCT-scans of 10 post-pubertal
      patients were randomly selected. Two operators identified the landmarks,
      calculated the airway volumes, cross sections and linear measurements on the 10
      scans twice at two different time intervals. Statistical analysis included test
      for normal distribution, technical error measurements, and intra- and inter
      observers reliability. RESULTS: Intra- and inter-observer reliability was
      excellent for volumes and cross sections. The entire data sets exhibited normal
      distribution. Technical error of measurements showed an error in the range of 1.6
      to 10.2% for volume, 1.6 to 12.2% for cross-sectional measurements, and 0.3 to
      2.5% for linear measurements. No systematic errors were detected. CONCLUSIONS:
      This new proposed definition of upper airway boundaries was shown to be technical
      feasible and tested to be reliable in measuring upper airway in patients
      undergoing orthognathic surgery.

PMID- 28749704
TI  - Self-Medication for Sleep in College Students: Concurrent and Prospective
      Associations With Sleep and Alcohol Behavior.
AB  - OBJECTIVE/BACKGROUND: College students are at an increased risk for poor sleep
      and associated sleep problems. Emerging evidence suggests that a substantial
      subset of college students self-medicate with alcohol, marijuana, or over-the
      counter medications to help sleep. The current study identified demographic,
      psychosocial, and sleep- and alcohol-related correlates of self-medication for
      sleep, and assessed its concurrent and prospective associations with insomnia
      symptoms, alcohol drinking, and negative drinking consequences. PARTICIPANTS:
      Undergraduate students (N = 171; mean age = 19 years [SD = 1.35], 32% male, 74%
      White) enrolled in a four-year university in the northeastern United States.
      METHODS: Data were drawn from a short-term two-wave longitudinal study.
      Participants completed two online surveys, separated by an average interval of 68
      days (SD = 10.22). RESULTS: At Time 1, 25% of students reported using at least
      one substance (alcohol, marijuana, or over-the-counter medications) for sleep aid
      in the past two weeks. Male and older students were more likely to report using
      substances for sleep. Sleep aid use at Time 1 was concurrently associated with
      greater levels of alcohol frequency, negative drinking consequences, and insomnia
      symptoms. Further, sleep aid use at Time 1 was associated with an increase in
      negative drinking consequences from Time 1 to Time 2, but not with changes in
      alcohol frequency or insomnia symptoms. CONCLUSIONS: These findings indicate that
      substances are widely used among college students for sleep aid. Sleep aid use is
      associated with greater concurrent drinking and insomnia symptoms, and increases
      in negative drinking consequences over a short time period.

PMID- 28749705
TI  - Associations Between Postpartum Depression, Breastfeeding, and Oxytocin Levels in
      Latina Mothers.
AB  - BACKGROUND: Postpartum depression (PPD), often comorbid with anxiety, is the
      leading medical complication among new mothers. Latinas have elevated risk of
      PPD, which has been associated with early breastfeeding cessation. Lower plasma
      oxytocin (OT) levels have also been associated with PPD in non-Latinas. This
      pilot study explores associations between PPD, anxiety, breastfeeding, and OT in
      Latinas. MATERIALS AND METHODS: Thirty-four Latinas were enrolled during their
      third trimester of pregnancy and followed through 8 weeks postpartum. Demographic
      data were collected at enrollment. Depression was assessed using the Edinburgh
      Postnatal Depression Scale (EPDS) at each time point (third trimester of
      pregnancy, 4 and 8 weeks postpartum). The Spielberger State-Trait Anxiety
      Inventory (STAI) was administered postpartum and EPDS anxiety subscale was used
      to assess anxiety at each time point. Breastfeeding status was assessed at 4 and
      8 weeks postpartum. At 8 weeks, OT was collected before, during, and after a 10
      minute breast/bottle feeding session from 28 women who completed the procedures.
      Descriptive statistics are provided and comparisons by mood and breastfeeding
      status were conducted. Analyses of variance were used to explore associations
      between PPD, anxiety, breastfeeding status, and OT. RESULTS: Just under one-third
      of women were depressed at enrollment. Prenatal depression, PPD, and anxiety were
      significantly associated with early breastfeeding cessation (i.e., stopped
      breastfeeding before 2 months) (p < 0.05). There was a significant interaction
      between early breastfeeding cessation and depression status on OT at 8 weeks
      postpartum (p < 0.05). CONCLUSIONS: Lower levels of OT were observed in women who
      had PPD at 8 weeks and who had stopped breastfeeding their infant by 8 weeks
      postpartum. Future studies should investigate the short- and long-term effects of
      lower OT levels and early breastfeeding cessation on maternal and child well
      being.

PMID- 28749706
TI  - Medication Information Sources for Breastfeeding Mothers.

PMID- 28749707
TI  - Imaging findings of Alagille syndrome in young infants: differentiation from
      biliary atresia.
AB  - OBJECTIVE: To compare the imaging findings using ultrasonography, MR
      cholangiopancreatography (MRCP), and intraoperative cholangiography (IOC) between
      Alagille syndrome (AGS) and biliary atresia (BA) in young infants with
      cholestatic jaundice. METHODS: The institutional review board approved this
      retrospective study. Ultrasonography (n = 55), MRCP (n = 33), and IOC (n = 22)
      studies were performed in 55 infants (all younger than 3 months) with AGS (n = 7)
      and BA (n = 48). The ultrasound images were reviewed focusing on gallbladder (GB)
      abnormalities, triangular cord sign, hepatic artery enlargement and signs of
      portal hypertension. Visualization of the extrahepatic biliary tree was assessed
      by MRCP and IOC. RESULTS: Six (86%) AGS patients showed a small GB on ultrasound;
      this was comparable to that in BA patients (81%, 35/43). The images were negative
      for triangular cord sign and hepatic artery enlargement in all AGS patients,
      whereas they were positive in 48% (23/48) (p = 0.034) and 77% (33/43) (p < 0.001)
      of the BA patients, respectively. Signs of portal hypertension were less common
      in AGS patients than in BA patients (p = 0.010). Although non-visualization of
      the extrahepatic biliary tree by MRCP did not differ significantly between
      patients with AGS and BA, AGS patients showed a higher proportion of visible
      common bile ducts with IOC, compared to BA patients. The diagnosis of AGS was
      made in four infants (57%) before ultrasonography, based on extrahepatic
      manifestations. CONCLUSION: The small GB visualized on ultrasonography and non
      visualization of extrahepatic biliary tree by MRCP commonly occurred in patients
      with either AGS or BA. However, triangular cord sign, hepatic artery enlargement
      and signs of portal hypertension onultrasonography and non-visualized common bile
      duct with IOC were less frequent in AGS patients than in BA patients. Advances in
      knowledge: Atypical imaging findings for BA should prompt a meticulous evaluation
      for the extrahepatic manifestations of AGS to avoid possibly harmful surgery.

PMID- 28749708
TI  - SMG-1 kinase attenuates mitochondrial ROS production but not cell respiration
      deficits during hyperoxia.
AB  - PURPOSE: Supplemental oxygen (hyperoxia) used to treat individuals in respiratory
      distress causes cell injury by enhancing the production of toxic reactive oxygen
      species (ROS) and inhibiting mitochondrial respiration. The suppressor of
      morphogenesis of genitalia (SMG-1) kinase is activated during hyperoxia and
      promotes cell survival by phosphorylating the tumor suppressor p53 on serine 15.
      Here, we investigate whether SMG-1 and p53 blunt this vicious cycle of
      progressive ROS production and decline in mitochondrial respiration seen during
      hyperoxia. MATERIALS AND METHODS: Human lung adenocarcinoma A549 and H1299 or
      colon carcinoma HCT116 cells were depleted of SMG-1, UPF-1, or p53 using RNA
      interference, and then exposed to room air (21% oxygen) or hyperoxia (95%
      oxygen). Immunoblotting was used to evaluate protein expression; a Seahorse
      Bioanalyzer was used to assess cellular respiration; and flow cytometry was used
      to evaluate fluorescence intensity of cells stained with mitochondrial or redox
      sensitive dyes. RESULTS: Hyperoxia increased mitochondrial and cytoplasmic ROS
      and suppressed mitochondrial respiration without changing mitochondrial mass or
      membrane potential. Depletion of SMG-1 or its cofactor, UPF1, significantly
      enhanced hyperoxia-induced mitochondrial but not cytosolic ROS abundance. They
      did not affect mitochondrial mass, membrane potential, or hyperoxia-induced
      deficits in mitochondrial respiration. Genetic depletion of p53 in A549 cells and
      ablation of the p53 gene in H1299 or HCT116 cells revealed that SMG-1 influences
      mitochondrial ROS through activation of p53. CONCLUSIONS: Our findings show that
      hyperoxia does not promote a vicious cycle of progressive mitochondrial ROS and
      dysfunction because SMG-1-p53 signaling attenuates production of mitochondrial
      ROS without preserving respiration. This suggests antioxidant therapies that
      blunt ROS production during hyperoxia may not suffice to restore cellular
      respiration.

PMID- 28749709
TI  - LncRNA HOXA11-AS Exerts Oncogenic Functions by Repressing p21 and miR-124 in
      Uveal Melanoma.
AB  - Long noncoding RNAs (lncRNAs) have been reported to play vital roles in various
      human cancers. The aim of this study was to explore the critical role of lncRNA
      HOXA11-AS in uveal melanoma (UM) progression. Briefly, we found that HOXA11-AS is
      overexpressed in UM tissues and cells; HOXA11-AS could regulate UM cell growth,
      invasion, and apoptosis. Mechanistically, RNA immunoprecipitation demonstrated
      that HOXA11-AS could simultaneously interact with enhancer of zeste homolog 2
      (EZH2) to suppress its target p21 protein expression. In addition, we
      demonstrated that HOXA11-AS functioned as a molecular sponge for miR-124, and
      overexpression of miR-124 attenuated the proliferation and invasion-promoting
      effect of HOXA11-AS. Collectively, our findings reveal an oncogenic role for
      HOXA11-AS in UM tumorigenesis.

PMID- 28749710
TI  - First Food Justice: Infant Feeding Disparities and the First Food System.
AB  - Breastfeeding and first foods--including human milk and infant formula--affect us
      all as individuals and a society of eaters and feeders. They also shape us in
      part through having significant effects on community health and well-being,
      workplace strength, and environmental integrity. In addition, we all affect
      breastfeeding and first foods. Society, the economy, and the environment
      constrain and enable breastfeeding success, for example, and they often do so
      differently by race, class, and other social categories. It is important we
      recognize and address these realities for our own individual interests as well as
      those we as a citizenry hold in common.

PMID- 28749711
TI  - Innate Sensing of HIV-1 by Dendritic Cell-Specific ICAM-3 Grabbing Nonintegrin on
      Dendritic Cells: Degradation and Presentation Versus Transmission of Virus to T
      Cells Is Determined by Glycan Composition of Viral Envelope.

PMID- 28749712
TI  - Lung cancer screening-low dose CT for lung cancer screening: recent trial results
      and next steps.
AB  - Screening for lung cancer using low-dose CT has already been implemented in North
      America following the results of the National Lung Screening Trial. Outside North
      America, clinicians and researchers are addressing issues that may have a major
      impact on the success of screening programmes by reviewing results of existing
      trials and by designing new research and pilot programmes. This review summarizes
      the work that has been done to try to answer the remaining questions and
      highlights potential barriers which may affect screening uptake and cost
      effectiveness.

PMID- 28749713
TI  - Safety considerations surrounding use of treatment options for nausea and
      vomiting in pregnancy.
AB  - INTRODUCTION: Nausea and vomiting of pregnancy (NVP) is the most prevalent
      medical condition during gestation, affecting up to 85% of pregnant women. Many
      of them hesitate to use medications due to perceived fetal risks. Areas covered:
      There are two main aspects to medication safety in NVP: The fetal safety of drugs
      used to treat NVP symptoms, and the risks of untreated NVP. While mild and
      moderate NVP are not associated with major increase in fetal or maternal risks,
      and may render protective fetal effects, they have major impact on the quality of
      life of the mother. In contrast, severe NVP and hyperemesis gravidarum (HG) are
      associated with increased maternal and fetal risks, from in utero growth
      restriction to developmental delay. For the doxylamine/pyridoxine combination,
      H1blockers and metoclopramide there are large studies documenting fetal safety.
      There are also large reassuring studies on the fetal safety of ondansetron, but
      they are contrasted by some studies claiming increased fetal risk. Expert
      opinion: Fetal safety of the doxylamine/pyridoxine combination, H1blockers and
      for metoclopramide has been documented. Reassuring studies on the fetal safety of
      ondansetron, are contrasted by some studies claiming increased teratogenicity.
      More studies are needed to quantify fetal risks of HG.

PMID- 28749714
TI  - Risk Factors for Carbapenem-Resistant Klebsiella pneumoniae Infection: A Meta
      Analysis.
AB  - AIMS: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has been
      rapidly emerging as a life-threatening nosocomial disease in many countries.
      However, studies on the corresponding risk factors of CRKP infection showed
      inconsistent results. To resolve these inconsistencies, we conducted a meta
      analysis of previous studies on the potential risk factors of CRKP infection. The
      results of this study could be used to develop CRKP infection prevention
      strategies. METHODS: Relevant works were systematically searched from five
      electronic databases up to September 2016. Z-test was used to determine the
      significance of the pooled odds ratios (ORs). ORs and 95% confidence intervals
      were utilized to compare the risk factors of CRKP infection. RESULTS: Sixteen
      studies that involved 3,627 participants were included in the meta-analysis. We
      identified the following risk factors that were associated with CRKP infection:
      (1) longer length of hospital stay (LOS) (OR = 12.92), (2) admission to intensive
      care unit (ICU) (OR = 2.48), (3) prior hospitalization (OR = 1.85), (4) longer
      days of ICU stay (OR = 4.58), (5) transplant recipient (OR = 2.01), (6) steroid
      use (OR = 1.43), (7) central venous catheter use (OR = 2.30), (8) mechanical
      ventilation (OR = 2.54), (9) presence of tracheostomy (OR = 3.63), (10)
      parenteral nutrition (OR = 2.38), (11) previous antibiotic use (OR = 3.31), and
      (12) exposure to carbapenems (OR = 4.01), (13) aminoglycosides (OR = 2.05), (14)
      glycopeptides (OR = 2.40), (15) quinolones (OR = 2.28), and (16) anti-pseudomonal
      penicillins (OR = 2.67). CONCLUSIONS: Sixteen risk factors including longer LOS,
      admission to ICU, previous antibiotic use, and exposure to carbapenems were
      associated with the development of CRKP infection. Identification of modifiable
      risk factors could play an important role in the prevention of CRKP infection.

PMID- 28749715
TI  - Insomnia and Autonomic Function Predict Well-Being in Patients Receiving
      Palliative Care.
AB  - BACKGROUND: The improvement of health-related quality of life (HRQOL) is one of
      the main treatment goals in end-of-life care. Although definitions and
      conceptualizations remain heterogeneous, many researchers proposed HRQOL to be
      considered as subjective patient well-being. However, research on its
      determinants in palliative care is rare, and little is known about the interplay
      between psychological and biological variables. OBJECTIVE: The aim of this study
      was to explain differences in terminally ill patients' acute well-being (AWB) by
      use of a multimethod approach, examining both self-ratings and physiological
      predictors. SETTING/SUBJECTS: The study was conducted on a palliative care unit
      in Heidelberg, Germany. A total of 69 adult patients receiving palliative care
      were included in the analysis. MEASUREMENTS: Patients filled out the EORTC QLQ
      C15-PAL questionnaire and an additional single-item visual analogue scale on AWB.
      In addition, we recorded a five-minute segment of beat-to-beat fluctuations of
      heart rate (i.e., heart rate variability, HRV) and calculated three indices of
      cardiac autonomic function: mean heart rate, the root mean square of successive
      differences, and the standard deviation of normal-to-normal (SDNN) intervals.
      Exploratory, multiple regression analyses were used to identify significant
      predictors among the QLQ subscales and HRV parameters. RESULTS: Insomnia (p <
      0.001) and SDNN (p < 0.001) were significantly associated with AWB and together
      explained 26.3% of the variance. All other predictors including pain, fatigue,
      and physical functioning failed to reach significance (all p > 0.05). CONCLUSION:
      Both autonomic dysfunction and sleep disturbances independently explained
      differences in patient's AWB among terminally ill patients. Their role within the
      concept of quality of life needs to be further addressed in future studies.

PMID- 28749716
TI  - Predilection to Dermato-Lymphangio-Adenitis in Obstructive Lymphedema of Lower
      Limbs Depending on Genetic Polymorphisms at TNFalpha-308G>A, CCR2-190G>A, CD14
      159C>T, TLR2 2029C>T, TLR4 1063A>G, TLR4 1363C>T, TGFbeta 74G>C, and TGFbeta
      29T>C.
AB  - BACKGROUND: Infection is the most common type of complication observed in
      lymphedema and is promoted by lymphatic system dysfunction, which causes
      locoregional immune disorders. Infectious complications are primarily bacterial
      and most commonly cellulitis (dermato-lymphangio-adenitis, DLA) caused by
      patients' own skin Staphylococci epidermidis and aureus. The clinical course and
      outcomes in the immune response to infection have been shown to be associated
      with genetic polymorphisms. AIM: To investigate polymorphism of TNFalpha-308G>A,
      CCR2-190G>A, CD14-159C>T, TLR2 2029C>T, TLR4 1063A>G, TLR4 1363C>T, TGFbeta
      74G>C, and TGFbeta 29T>C. The second part of study was the correlation of levels
      of TNFalpha and TGFbeta with their genes polymorphism in one hundred patients
      with lower limb postdermatitis lymphedema. RESULTS: (a) High percentage of
      TNFalpha homozygotes, no differences in genotypes of CD14-159C>T, CCR2-190G>A,
      TGFbeta 74G>C, TGFbeta 29T>C, and TLR4 1063A>G, low percentage of TLR2 2029C>T
      heterozygotes and homozygotes TT, and a high percentage of TLR4 1363C>T
      homozygotes TT, (b) low serum levels of TGFbeta and TNFalpha in 19% and 43% of
      patients, respectively, however, lack of correlation between low levels of these
      cytokines and frequency of homozygotes CC and AA, respectively. CONCLUSIONS: The
      practical implications of finding high frequency of genotype TT of TLR4 1363C>T
      are indications for testing this gene in patients with obstructive lymphedema of
      lower limbs and early antibiotic prophylaxis of recurrent attacks of DLA, and
      during elective surgery of lymphedema. The obtained data are also important as a
      contribution to mapping of genetic variations in acquired lymphedema of lower
      limbs.

PMID- 28749717
TI  - Circumference-Based Criteria for Detection of Secondary Arm Lymphedema for
      Chinese Women.
AB  - BACKGROUND: Detection of upper limb lymphedema following treatment for breast
      cancer typically relies on interlimb circumference-based differences. Normative
      determined criteria from an Australian population have high sensitivity and
      specificity for detection of mild lymphedema in Australian women. It is unknown
      whether these criteria are applicable to Chinese women whose body habitus is
      different from Australian women. The aims of this study, therefore, were to
      determine the normative-based interlimb circumference and volume differences in a
      Chinese population and whether specific population-based thresholds are required.
      METHODS AND RESULTS: Arm circumferences at the wrist and at 10 cm intervals
      proximally to 40 cm were measured on both the dominant and nondominant limb in
      484 healthy women, aged >=20 years. Absolute interlimb differences and interlimb
      ratios were determined for the circumferences and derived 10 cm volume segments.
      Analysis of variance determined if the differences varied, depending on location.
      The absolute interlimb circumference difference from 10 to 30 cm did not vary
      significantly, enabling determination of a single threshold applicable to all
      three circumferences. The interlimb ratios varied less, requiring only a
      threshold for the wrist and one for 10-40 cm and one ratio for interlimb volume
      segments. The interlimb thresholds determined in the Chinese population were
      within 2 mm to that reported in the Australian study. CONCLUSIONS: Even though
      the habitus of Chinese women living in China differed to the women living in
      Australia, similar normative-based thresholds for the detection of lymphedema
      were identified.

PMID- 28749718
TI  - Ectopic Intralaryngo-Tracheal Thyroid Tissue Causing Neonatal Death.
AB  - INTRODUCTION: Ectopic thyroid tissue can be found anywhere along the embryologic
      path of thyroid descent. Intralaryngo-tracheal thyroid tissue is the least common
      site of ectopia and can present with upper airways obstruction. Its presentation
      in the neonate is exceptional. CASE REPORT: We describe a term female neonate
      with subglottic thyroid tissue causing near-total occlusion of the larynx, which
      led to upper airways obstruction and neonatal death. CONCLUSION: This emphasizes
      the importance of considering intralaryngo-tracheal tumors as a cause of acute
      and otherwise unexplainable respiratory distress immediately after birth. The
      cause of this neonatal death would not have been elucidated without careful
      autopsy examination.

PMID- 28749719
TI  - Targeting the myocardium in hypertensive left ventricular hypertrophy.

PMID- 28749720
TI  - A Validation Study of Near-Infrared Fluorescence Imaging of Lymphatic Vessels in
      Humans.
AB  - BACKGROUND: Near-infrared fluorescence (NIRF) imaging is a new imaging technique
      that is used to visualize lymphatic vessels in humans. It has a high spatial and
      temporal resolution, allowing real-time visualization of lymphatic flow. METHODS
      AND RESULTS: The current study investigated the intra- and inter-individual
      variability of the technique, and how local hypo- and hyperthermia (20 degrees C,
      40 degrees C), as well as exercise affect lymph transport. In this study, 10
      healthy volunteers were studied twice, with 2 weeks between. NIRF imaging was
      conducted by using intradermal Indocyanine green injections and a custom-built
      camera setup. All data were blinded before analysis and presented as mean +/-
      standard deviation. Mean contraction frequency and lymph propulsion velocity were
      0.59 +/- 0.13 minutes-1 and 1.51 +/- 0.24 cm/s, respectively, with no significant
      difference during each 4 hours examination or between the two visits. The maximal
      pressure that the lymphatic flow in the vessels could overcome on test day 1 and
      2 was 56 +/- 9 mmHg and 57 +/- 9 mmHg, respectively (p = 0.496). Local
      hyperthermia increased contraction frequency from 0.62 +/- 0.4 minutes to 1.46 +/
      0.5 minutes-1 (p < 0.05). Hypothermia caused no significant changes. Immediately
      after exercise (exercising at a simulated distance of 1.4 km on a cycle
      ergometer), an increase in lymph propulsion velocity from 1.5 +/- 0.49 to 2.2 +/-
      0.63 cm/s was observed (p < 0.05); whereas contraction frequency was unaltered. A
      decrease in contraction frequency from 0.68 +/- 0.25 minutes to 0.35 +/- 0.19
      minutes-1 was observed 10 minutes after exercise, without a change in velocity.
      CONCLUSIONS: NIRF imaging can be conducted for 4 hours without a change in
      lymphatic activity. Furthermore, it has the sensitivity to detect changes in
      lymphatic activity by local hyperthermia and exercise. No changes were seen after
      local hypothermia. Pumping pressure shows good repeatability, whereas the other
      parameters show poor repeatability.

PMID- 28749721
TI  - The Reliability of the Segmental Assessment of Trunk Control (SATCo) in Children
      with Cerebral Palsy.
AB  - AIMS: To assess the live-versus-video, intrarater interday and interrater
      interday reliability of the test Segmental Assessment of Trunk Control (SATCo),
      which seeks to estimate the degree of sitting trunk control in children with
      cerebral palsy (CP). METHOD: Thirty-one children with CP between 9 months and 16
      years of age (22 males, mean age 8y 10mo [SD 3y 5mo], Gross Motor Function
      Classification System level I [n = 13], II [n = 4], III [n = 4], IV [n = 3], and
      V [n = 7]) were included. Children were tested twice by two raters and tests were
      video recorded. Wilcoxon Signed-Rank Test, ICC [2,1] and a descriptive measure
      for absolute reliability were applied. RESULTS: No systematic differences were
      found between live-versus-video, between raters or days (p > 0.05) except for one
      analysis. All ICC values were excellent (ICC >= 0.9) except for one analysis for
      which it was good (ICC = 0.73). Complete agreement between scores was seen in 75%
      of all cases while 22% differed by one segmental level. Only 3% showed
      disagreement above one segmental level. CONCLUSIONS: SATCo is a clinically
      applicable assessment tool. Relative reliability is excellent and absolute
      agreement is good. Modifications regarding testing method could potentially
      improve the reliability and the value of the test in research and in clinical
      practice.

PMID- 28749722
TI  - Association Between Plasma Proprotein Convertase Subtilisin/Kexin Type 9 and the
      Presence of Metabolic Syndrome in a Predominantly Rural-Based Sub-Saharan African
      Population.
AB  - BACKGROUND: The prevalence of metabolic syndrome (MetS) has increased
      dramatically in low- and middle-income countries. Proprotein convertase
      subtilisin/kexin type 9 (PCSK9) plays a major role in low-density lipoprotein
      receptor degradation, but its relationship with metabolic parameters is still
      poorly understood. We aimed to investigate the association between plasma PCSK9
      and metabolic parameters in a Kenyan cohort. METHODS: Total plasma PCSK9 levels
      were measured in 2016 by an in-house enzyme-linked immunosorbent assay (ELISA)
      using a polyclonal antibody. The International Diabetes Federation (IDF) 2009
      consensus statement criteria were used to assess the presence of MetS. RESULTS:
      In 1338 Kenyans, 11% of the cohort had >=3 MetS criteria. Total plasma PCSK9
      concentration was significantly higher in subjects with MetS than in the non-MetS
      group (166.8 +/- 4.4 vs. 148.0 +/- 1.3, P < 0.0001). A progressive increase in
      circulating PCSK9 was observed when subjects were stratified according to the
      number of MetS criteria (<3, 3, 4, or 5) [P of the analysis of variance (ANOVA)
      <0.0001]. In a model corrected for age, sex, lifestyle factors, and body mass
      index, PCSK9 concentration was a significant predictor of all MetS criteria taken
      individually, except for waist circumference. Plasma PCSK9 levels were
      significantly associated with low-density lipoprotein cholesterol, but the
      strongest association was seen with triglycerides even after multiple
      adjustments. CONCLUSIONS: The presence of MetS was significantly associated with
      the PCSK9 concentration. Further studies are needed to provide a molecular
      connection between PCSK9 and insulin, as well as triglyceride metabolism.

PMID- 28749723
TI  - Measurement of Local Tissue Water in Patients with Breast Cancer-Related
      Lymphedema.
AB  - BACKGROUND: Studies revealed that having "1.20" or upper interarm local tissue
      water (LTW) ratio which can be calculated through tissue dielectric constant
      (TDC) method might be the determinant of clinical lymphedema after breast cancer
      surgery. The purpose of this study was to confirm these findings and determine
      the sensitivity and specificity of LTW (%) measurement method in patients with
      breast cancer related lymphedema (BCRL). METHODS AND RESULTS: Sixty-three
      participants were recruited to this study in two groups as follows: the
      lymphedema group (n = 32), who had BCRL after breast cancer surgery, and the
      latent group (n = 31), who had breast cancer surgery yet having no lymphedema.
      LTW (%) measurement of those was conducted with Moisture Meter-D compact (MMDc,
      Delfin Technologies, Kuopio, Finland) at sites 8 cm proximal (biceps) and 6 cm
      distal (forearm) from the antecubital fossa, 10 cm inferior from the axilla
      (lateral thorax) in 2.5 mm depth. Sensitivity and specificity of TDC method were
      analyzed based on the reference having 1.20 or upper interarm LTW ratio in both
      groups. RESULTS: Absolute LTW (%) values were significantly different (p < 0.001)
      between groups in forearm (latent: 26.96 +/- 3.35, lymphedema: 36.85 +/- 9.32)
      and in biceps (latent: 26.54 +/- 4.11, lymphedema: 36.45 +/- 9.91) while in
      lateral thorax reference point (latent: 35.22 +/- 7.44, lymphedema: 33.32 +/-
      5.08) there was not (p = 0.241). Interarm LTW ratios were significantly different
      (p < 0.001) between groups in forearm (latent: 1.01 +/- 0.06, lymphedema: 1.40 +/
      0.35) and in biceps (latent: 1.02 +/- 0.10, lymphedema: 1.42 +/- 0.38) while in
      lateral thorax reference point (latent: 1.10 +/- 0.25, lymphedema: 1.07 +/- 0.16)
      there was not (p = 0.896). Sensitivity and specificity of the TDC method were 65%
      and 94%, respectively. CONCLUSION: Absolute LTW (%) values and interarm LTW
      ratios were significantly different between patients with clinically diagnosed
      BCRL and patients with no BCRL (latent group). TDC method has been gradually
      gaining attention in clinical use and this method might be the preferable method
      in case of early detection of BCRL in patients in latent phase. Regular follow
      ups would be beneficial if objective and sensitive measurement techniques were
      done in clinical settings.

PMID- 28749724
TI  - Use of Surveillance Mammography Among Older Breast Cancer Survivors by Life
      Expectancy.
AB  - Purpose The benefits of annual surveillance mammography in older breast cancer
      survivors with limited life expectancy are not known, and there are important
      risks; however, little is known about mammography use among these women.
      Materials and Methods We used National Health Interview Study data from 2000,
      2005, 2008, 2010, 2013, and 2015 to examine surveillance mammography use among
      women age >= 65 years who reported a history of breast cancer. Using
      multivariable logistic regression, we assessed the probability of mammography
      within the last 12 months by 5- and 10-year life expectancy (using the validated
      Schonberg index), adjusting for survey year, region, age, marital status,
      insurance, educational attainment, and indicators of access to care. Results Of
      1,040 respondents, 33.7% were age >= 80 years and 88.6% were white. Approximately
      8.6% and 35.1% had an estimated life expectancy of <= 5 and <= 10 years,
      respectively. Overall, 78.9% reported having routine surveillance mammography in
      the last 12 months. Receipt of mammography decreased with decreasing life
      expectancy ( P < .001), although 56.7% and 65.9% of those with estimated <= 5
      year and <= 10-year life expectancy, respectively, reported mammography in the
      last year. Conversely, 14.1% of those with life expectancy > 10 years did not
      report mammography. In adjusted analyses, lower ( v higher) life expectancy was
      significantly associated with lower odds of mammography (odds ratio, 0.4; 95% CI,
      0.3 to 0.8 for <= 5-year life expectancy and OR, 0.4; 95% CI, 0.3 to 0.6 for <=
      10-year life expectancy). Conclusion Many (57%) older breast cancer survivors
      with an estimated short life expectancy (< 5 years) receive annual surveillance
      mammography despite unknown benefits, whereas 14% with estimated life expectancy
      > 10 years did not report mammography. Practice guidelines are needed to optimize
      and tailor follow-up care for older patients.

PMID- 28749725
TI  - Advocacy and luck: Australian healthcare experiences following a suicide attempt.
AB  - High quality mental healthcare after a suicide attempt is a key strategy for
      preventing subsequent suicide attempts and deaths, yet little is known about how
      people navigate the healthcare system following a suicide attempt. This paper
      focuses on the stories told by 20 people who had attempted suicide. Five themes
      emerged: fitting into the healthcare system; need for advocacy; consistent care;
      lucky to find help; and, small kindnesses. Positive and empathetic healthcare
      experiences, as well as connected services, assisted the recovery of people who
      have attempted suicide.

PMID- 28749726
TI  - The patch assay reconstitutes mature hair follicles by culture-expanded human
      cells.
AB  - AIM: We tested whether the a simple injection known as the patch assay could
      reconstitute mature hair follicles by culture-expanded human cells and explored
      whether the assay could reflect the trichogenicity of cultured cells. MATERIALS &
      METHODS: Dissociated culture-expanded fetal or adult scalp dermal cells combined
      with foreskin keratinocytes were subcutaneously injected into the back skin of
      immunosuppressive mice to form the patch skin. The patches were collected and
      characterized and were analyzed for hair formation efficiency. RESULTS: Using
      culture-expanded human fetal cells, the patch assay can efficiently reconstitute
      mature hair follicles and the efficiency of hair formation in the patch assay
      correlates with cell trichogenicity. CONCLUSION: The patch assay has the
      potential for testing the trichogenicity of human cells.

PMID- 28749727
TI  - Practice Innovation, Health Care Utilization and Costs in a Network of Federally
      Qualified Health Centers and Hospitals for Medicaid Enrollees.
AB  - State Medicaid programs need cost-effective strategies to provide high-quality
      care that is accessible to individuals with low incomes and limited resources.
      Integrated delivery systems have been formed to provide care across the
      continuum, but creating a shared vision for improving community health can be
      challenging. Medical Home Network was created as a network of primary care
      providers and hospital systems providing care to Medicaid enrollees, guided by
      the principles of egalitarian governance, practice-level care coordination, real
      time electronic alerts, and pay-for-performance incentives. This analysis of
      health care utilization and costs included 1,189,195 Medicaid enrollees. After
      implementation of Medical Home Network, a risk-adjusted increase of $9.07 or 4.3%
      per member per month was found over the 2 years of implementation compared with
      an increase of $17.25 or 9.3% per member per month, before accounting for the
      cost of care management fees and other financial incentives, for Medicaid
      enrollees within the same geographic area with a primary care provider outside of
      Medical Home Network. After accounting for care coordination fees paid to
      providers, the net risk-adjusted cost reduction was $11.0 million.

PMID- 28749728
TI  - Addressing the Cultural Challenges of Firearm Restriction in Suicide Prevention:
      A Test of Public Health Messaging to Protect Those at Risk.
AB  - OBJECTIVES: Reducing access to firearms as a suicide prevention strategy is
      limited in the US today because of divergent cultural attitudes and political
      contentiousness surrounding gun restrictions. This research examined the effects
      of culturally-specific suicide prevention messages on the likelihood of
      restricting firearm access during periods of suicide risk. METHODS: Focus groups
      and key informant interviews were conducted with rural gun owners in order to
      develop a suicide prevention message that highlighted the importance of
      restricting access to firearms during periods of risk without threatening second
      amendment concerns. The effectiveness of this gun culture message, relative to
      standard suicide prevention messaging and a control condition, was then tested
      with a national sample of gun owners. RESULTS: Relative to all other conditions,
      respondents who received our culturally-specific message in conjunction with
      standard suicide prevention content reported the greatest likelihood of taking
      steps to restrict access to firearms. This tendency was enhanced for individuals
      who were more politically conservative, lived in more rural areas, and supported
      gun rights to a stronger degree. CONCLUSIONS: Findings underscore the importance
      of attending to cultural factors in public health messaging. Messaging that
      respects the values of gun owners could hold promise in promoting firearm
      restriction for suicide prevention.

PMID- 28749729
TI  - Understanding the Role of Message Frames on African-American Willingness to
      Participate in a Hypothetical Diabetes Prevention Study.
AB  - The objective of this research was to evaluate the impact of message framing
      (e.g., highlighting health disparities vs. progress toward reducing disparities)
      on willingness to enroll in a hypothetical research study. African-American (AA,
      n = 1513) and White (n = 362) adults completed an online survey about diabetes,
      health behaviors including physical activity, and attitudes about research. AA
      participants were randomized to view a general message (same message as provided
      to all White participants) or 1 of 4 alternate messages that framed the need for
      people to participate in research in terms of race and/or health disparities.
      Among AAs, there were no differences in willingness to enroll in the study by
      message frame. However, individual characteristics including younger age, female
      sex, attitudes about research, a sense of obligation, and community
      responsibility were significant predictors of willingness to enroll in the study.
      AA participants who received the general message were equally willing as White
      participants to enroll in the study. Highlighting race and health disparities in
      study recruitment materials may not be needed to increase interest among AAs.
      Factors beyond race appear to be stronger motivators for participation. Unlike
      previous research, racial framing did not suppress motivation to enroll in our
      hypothetical study.

PMID- 28749730
TI  - Static versus dynamic kinematics in cyclists: A comparison of goniometer,
      inclinometer and 3D motion capture.
AB  - Kinematic measurements conducted during bike set-ups utilise either static or
      dynamic measures. There is currently limited data on reliability of static and
      dynamic measures nor consensus on which is the optimal method. The aim of the
      study was to assess the difference between static and dynamic measures of the
      ankle, knee, hip, shoulder and elbow. Nineteen subjects performed three separate
      trials for a 10-min duration at a fixed workload (70% of peak power output).
      Static measures were taken with a standard goniometer (GM), an inclinometer (IM)
      and dynamic three-dimensional motion capture (3DMC) using an eight camera motion
      capture system. Static and dynamic joint angles were compared over the three
      trials to assess repeatability of the measurements and differences between static
      and dynamic values. There was a positive correlation between GM and IM measures
      for all joints. Only the knee, shoulder and elbow were positively correlated
      between GM and 3DMC, and IM and 3DMC. Although all three instruments were
      reliable, 3D motion analysis utilised different landmarks for most joints and
      produced different means. Changes in knee flexion angle from static to dynamic
      are attributable to changes in the positioning of the foot. Controlling for this
      factor, the differences are negated. It was demonstrated that 3DMC is not
      interchangeable with GM and IM, and it is recommended that 3DMC develop
      independent reference values for bicycle configuration.

PMID- 28749731
TI  - Transfer of Patients in a Telestroke Network: What Are the Relevant Factors for
      Making This Decision?
AB  - : Background/Introduction: Current telestroke network consultations are focused
      on decision-making in the hyperacute stage of stroke management. The two main
      questions in telestroke consultations are whether thrombolysis should be
      initiated and whether the patient should be transferred to a hub hospital.
      Although guidelines exist for initiating intravenous thrombolytic therapy, the
      question of whether patients should be transferred is far more elusive. MATERIALS
      AND METHODS: In this study, we investigated the factors involved in the decision
      to transfer stroke patients to a hub hospital. We were particularly interested in
      identifying factors that promote or impede the transfer of patients. We enrolled
      1,615 cases of telestroke consultation of the University Hospital Jena. RESULTS:
      The two main factors that independently influenced the probability of
      transferring a patient were the patient's age and the identification of a
      proximal vessel occlusion. Interestingly, factors such as the severity of
      symptoms and the time elapsed from symptom onset were not found to have an
      independent influence on the decision to transfer a patient. The transfer of most
      patients was justified by the possibility of performing interventional
      reperfusion therapy. DISCUSSION: We discuss the effectiveness of the current
      decision-making process and possible ways to improve decision-making for a more
      effective selection of patients who would benefit from transfer. CONCLUSION: The
      decision-making process to a transfer patient is not standardized and constitutes
      a trade-off between the intention to treat all possible patients while avoiding
      the transfer of patients without treatment options.

PMID- 28749732
TI  - Lack of association between cystatin C and different coronary atherosclerotic
      manifestations.
AB  - Cystatin C (CysC) is known to be related to cardiovascular disease (CVD),
      including the presence and severity of coronary artery disease (CAD) and future
      clinical events. In this study, the association between CysC levels and (1)
      coronary artery calcification (CAC) in asymptomatic individuals from the general
      population as well as (2) different subgroups of patients with suspected or
      definite acute myocardial infarction (MI) was investigated. CysC levels were
      measured in serum from asymptomatic individuals as part of a screening study for
      CAC using non-contrast cardiac CT scan (N = 1039) as well as in subgroups of
      hospitalized patients with a suspected MI (N = 769). CysC was not associated with
      CAC in asymptomatic individuals after adjusting for relevant risk factors. No
      difference in CysC levels was observed between patients with type 1 MI (1.07
      mg/L) and patients with normal troponin (with or without prior CAD: 1.14 and 1.01
      mg/L, respectively). However, patients with type 2 MI and patient subgroups with
      elevated troponin but without MI had significantly higher CysC levels (1.24, 1.23
      and 1.31 mg/L), even after adjusting for other risk factors. CysC was not
      associated with CAC in middle-aged asymptomatic individuals from the general
      population. Furthermore, CysC levels were found to be significantly lower in
      patients with type 1 MI compared to patients with type 2 MI and patients with
      elevated troponins but without MI. Thus, in two independent and clinically
      different populations, no association between CysC and coronary atherosclerotic
      manifestations could be demonstrated.

PMID- 28749733
TI  - Cytogenetic surveillance of persons occupationally exposed to genotoxic
      chemicals.
AB  - Human genotoxic exposures can occur environmentally, occupationally, or
      medicinally. The aim of this study was to assess cytogenetic damage (chromosomal
      aberrations and micronuclei) in persons exposed to chemical agents in medical,
      agricultural, and industrial occupations. The results showed influences of age,
      gender, occurrence, and duration of exposure on the extent of cytogenetic damage,
      but no influence of smoking. Persons exposed to pesticides were allocated
      significantly higher values of most examined parameters. Among all tested
      parameters, logistic regression analysis marked tMN, CB, and iCB as the best
      predictors with high discrimination accuracy of separation between exposed and
      unexposed persons. The obtained data encourage us to consider certain cytogenetic
      parameters as valuable markers for preventive medical screening as the extent of
      cytogenetic damage reflects cumulative exposure events and possible health
      consequences related to chronic occupational genotoxic exposure.

PMID- 28749734
TI  - Comparison of the effect of lavender and bitter orange on sleep quality in
      postmenopausal women: A triple-blind, randomized, controlled clinical trial.
AB  - This trial compared the effects of lavender and bitter orange on sleep quality in
      postmenopausal women. This trial was conducted in 2015. Eligible postmenopausal
      women were allocated into one of two intervention groups or a control group (n =
      52 per group) in a 1:1:1 ratio using a randomized block design. Intervention
      groups received 500 mg capsules containing only bitter orange or lavender flower
      powder, and the control group received 500 mg capsules containing starch. The
      Pittsburgh Sleep Quality Inventory was used before and eight weeks after starting
      the intervention. Data analyses were based on intention to treat. A one-way ANOVA
      showed a slightly significant difference in mean sleep score among the three
      groups before the intervention (p = .045). The general linear model, adjusted for
      baseline sleep score and confounding factors, showed significant differences
      among the groups in the mean sleep score after eight weeks of treatment (p <
      .001). Bitter orange and lavender significantly improved the mean sleep score
      compared with the control group (p < .001 and p = .003, respectively). The
      positive effect of bitter orange and lavender on sleep quality in postmenopausal
      women suggests that they can be used to improve sleep quality in such women.

PMID- 28749735
TI  - The Discovery, Mechanisms, and Evolutionary Impact of Anti-CRISPRs.
AB  - Bacteria and archaea use CRISPR-Cas adaptive immune systems to defend themselves
      from infection by bacteriophages (phages). These RNA-guided nucleases are
      powerful weapons in the fight against foreign DNA, such as phages and plasmids,
      as well as a revolutionary gene editing tool. Phages are not passive bystanders
      in their interactions with CRISPR-Cas systems, however; recent discoveries have
      described phage genes that inhibit CRISPR-Cas function. More than 20 protein
      families, previously of unknown function, have been ascribed anti-CRISPR
      function. Here, we discuss how these CRISPR-Cas inhibitors were discovered and
      their modes of action were elucidated. We also consider the potential impact of
      anti-CRISPRs on bacterial and phage evolution. Finally, we speculate about the
      future of this field.

PMID- 28749736
TI  - Cluster signal-to-noise analysis for evaluation of the information content in an
      image.
AB  - OBJECTIVES: (1) To develop an observer-free method of analysing image quality
      related to the observer performance in the detection task and (2) to analyse
      observer behaviour patterns in the detection of small mass changes in cone-beam
      CT images. METHODS: 13 observers detected holes in a Teflon phantom in cone-beam
      CT images. Using the same images, we developed a new method, cluster signal-to
      noise analysis, to detect the holes by applying various cut-off values using
      ImageJ and reconstructing cluster signal-to-noise curves. We then evaluated the
      correlation between cluster signal-to-noise analysis and the observer performance
      test. We measured the background noise in each image to evaluate the relationship
      with false positive rates (FPRs) of the observers. Correlations between mean FPRs
      and intra- and interobserver variations were also evaluated. Moreover, we
      calculated true positive rates (TPRs) and accuracies from background noise and
      evaluated their correlations with TPRs from observers. RESULTS: Cluster signal-to
      noise curves were derived in cluster signal-to-noise analysis. They yield the
      detection of signals (true holes) related to noise (false holes). This method
      correlated highly with the observer performance test (R2 = 0.9296). In noisy
      images, increasing background noise resulted in higher FPRs and larger intra- and
      interobserver variations. TPRs and accuracies calculated from background noise
      had high correlation with actual TPRs from observers; R2 was 0.9244 and 0.9338,
      respectively. CONCLUSIONS: Cluster signal-to-noise analysis can simulate the
      detection performance of observers and thus replace the observer performance test
      in the evaluation of image quality. Erroneous decision-making increased with
      increasing background noise.

PMID- 28749737
TI  - Improved Chondrogenic Potential and Proteomic Phenotype of Porcine Chondrocytes
      Grown in Optimized Culture Conditions.
AB  - For successful cartilage tissue engineering, the ability to generate a high
      number of chondrocytes in vitro while avoiding terminal differentiation or de
      differentiation is critical. The ability to accomplish this by using the abundant
      and easily sampled costal cartilage could provide a practical alternative to the
      use of articular cartilage and mesenchymal stem cells. Chondrocytes isolated from
      pig costal cartilage were expanded in either serum-free medium with FGF2 (SFM) or
      fetal bovine serum-containing medium (SCM), under either high (21%) or low (5%)
      oxygen conditions. Overall, chondrocytes cultured in SFM and low oxygen (Low-SFM)
      demonstrated the highest cell growth rate (p < 0.05). The effect of passage
      number on the differentiation status of the chondrocytes was analyzed by alkaline
      phosphatase (AP) staining and real-time PCR for known chondrocyte quality
      markers. AP staining indicated that chondrocytes grown in SCM had a higher
      proportion of terminally differentiated (hypertrophic) chondrocytes (p < 0.05).
      At the mRNA level, expression ratios of ACAN/VCAN and COL2/COL1 were
      significantly higher (p < 0.05) in cells expanded in Low-SFM, indicating reduced
      de-differentiation. In vitro re-differentiation capacity was assessed after a 6
      week induction, and chondrocytes grown in Low-SFM showed similar expression
      ratios of COL2/COL1 and ACAN/VCAN to native cartilage. Proteomic analysis of in
      vitro produced cartilage indicated that the Low-SFM condition most closely
      matched the proteomic profile of native costal and articular cartilage. In
      conclusion, Low-SFM culture conditions resulted in improved cell growth rates,
      reduced levels of de-differentiation during expansion, greater ability to re
      differentiate into cartilage on induction, and an improved proteomic profile that
      resembles that of in vivo cartilage.

PMID- 28749738
TI  - Nutraceutical Potential of New Alfalfa (Medicago sativa) Ingredients for Beverage
      Preparations.
AB  - Alfalfa (Medicago sativa) has been extensively used as animal feed, due to its
      fiber, protein, minerals, and vitamins, being also a useful source of phenolic
      compounds with potential therapeutic benefits. Nevertheless, its potential use as
      human ingredient is scarce. The aim of this work was to assess the nutritional
      composition, amino acid profile, and antioxidant capacity (AOC) of freeze-dried
      juice (FDJ) and fibrous residual material (RM), two new alfalfa-derived products
      (Adps) recently launched as ingredients for beverage preparations. Results
      demonstrated a high content of proteins (23-30 g/100 g FDJ and 13-17 g/100 g RM),
      crude fiber (29 g/100 g RM), and minerals (such as sodium, calcium, iron, and
      zinc). No significant difference was found in caloric content (4 kcal/g).
      Essential and nonessential amino acids were quantified in both Adps being leucine
      and lysine the most abundant. Total phenolic and total flavonoid contents (TPC
      and TFC, respectively) and their changes along the different harvesting periods
      of the year were also examined. FDJ presented the highest TPC in May (19 mg
      gallic acid equivalents/g dry weight [dw]), while in October TFC had the maximum
      value (4 mg catechin equivalents/g dw). Both products exhibited an interesting
      AOC by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power
      assays. This study reports the nutraceutical potential of two new types of Adps.

PMID- 28749739
TI  - Nanomedicine formulations for the delivery of antiviral drugs: a promising
      solution for the treatment of viral infections.
AB  - INTRODUCTION: Viral infections represent a public health problem and one of the
      leading causes of global mortality. Nanomedicine strategies can be considered a
      powerful tool to enhance the effectiveness of antiviral drugs, often associated
      with solubility and bioavailability issues. Consequently, high doses and frequent
      administrations are required, resulting in adverse side effects. To overcome
      these limitations, various nanomedicine platforms have been designed. Areas
      covered: This review focuses on the state of the art of organic-based
      nanoparticles for the delivery of approved antivirals. A brief description of the
      main characteristics of nanocarriers is followed by an overview of the most
      promising research addressing the treatment of most important viral infections.
      Expert opinion: The activity of antiviral drugs could be improved with
      nanomedicine formulations. Indeed, nanoparticles can affect the fate of the
      encapsulated drugs, allowing controlled release kinetics, enhanced
      bioavailability, modified pharmacokinetics, and reduced side effects. In
      addition, the physicochemical properties of nanocarriers can enable their
      capability to target specific sites and to interact with virus structures. In
      this regard, nanomedicines can be considered an opportunity to enhance the
      therapeutic index of antivirals. Efficacy, safety, and manufacturing issues need
      to be carefully assessed to bring this promising approach to the clinic.

PMID- 28749740
TI  - The role of high-sensitivity C-reactive protein levels in functional outcomes in
      patients with large-artery atherosclerosis and small-artery occlusion.
AB  - BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is an inflammatory
      marker that is associated with the outcomes of ischemic stroke. However, the role
      of hs-CRP levels in the functional outcomes after large-artery atherosclerosis
      (LAA) and small-artery occlusion (SAO) is poorly understood. METHODS: We
      recruited 1299 patients diagnosed as having LAA and 453 patients diagnosed as
      having SAO from 1 January 2009 to 31 December 2013, from the Department of
      Neurology, Tianjin Huanhu Hospital. The hs-CRP values were classified into two
      groups based on the significant threshold of hs-CRP level in the receiver
      operating characteristic (ROC) curve (>=3.215 mg/L in LAA and >=1.72 mg/L in
      SAO). We examined the relationship between hs-CRP levels on admission and the
      modified Rankin scale scores using univariate and multivariate analyses. RESULTS:
      Patients with LAA had a higher hs-CRP mean value than patients with SAO (7.69 vs.
      4.12 mg/L). The ROC curve showed a significant hs-CRP threshold value at 3.215
      mg/L in patients with LAA and at 1.72 mg/L in patients with SAO. Logistic
      regression analyses showed that patients with LAA with hs-CRP levels >=3.215 mg/L
      had a significant risk of poor outcome compared with those with hs-CRP levels
      <3.215 mg/L (odds ratio [OR], 1.545; 95% confidence interval [CI], 1.155-2.067; p
      = 0.003). Meanwhile, patients with SAO with hs-CRP levels >=1.72 mg/L had a
      significant risk of poor outcome compared with those with hs-CRP levels <1.72
      mg/L (OR, 1.97; 95% CI, 1.02-3.801; p = 0.043). Moreover, combining hs-CRP with
      National Institutes of Health Stroke Scale could predict outcome with satisfying
      clinical accuracy both in LAA and SAO subtype. CONCLUSIONS: Patients with LAA
      with hs-CRP levels <3.215 mg/L and patients with SAO with hs-CRP levels <1.72
      mg/L on admission had favorable functional outcomes at 3 months after stroke
      onset.

PMID- 28749741
TI  - Pectoralis Major Repair: A Biomechanical Analysis of Modern Repair Configurations
      Versus Traditional Repair Configuration.
AB  - BACKGROUND: Pectoralis major (PM) ruptures are increasingly common, and a variety
      of surgical techniques have been described. However, tested techniques have
      demonstrated diminished strength with inadequate restoration of the footprint and
      suture failure at relatively low loads. Purpose/Hypothesis: The purpose was to
      biomechanically compare PM transosseous suture repair (current gold standard) to
      modern PM repair techniques that use larger caliber sutures, suture tape, and
      unicortical button fixation (UBF). The null hypothesis was that there would be no
      mechanical difference between repair techniques and no difference in the amount
      of footprint restoration. STUDY DESIGN: Controlled laboratory study. METHODS:
      Twenty-four fresh-frozen cadaveric shoulders controlled for age and bone mineral
      density were randomized equally to 4 groups: (1) UBF, suture tape; (2) UBF, No. 5
      suture, suture tape; (3) bone trough with No. 2 suture; and (4) native PM tendon
      group; all groups were tested to failure. The specimens were tested under cycling
      loads (10 N to 125 N) with a final load-to-failure test at 1 mm/s. Failure modes
      were classified by location and cause of rupture based on optical markers, while
      tendon footprint length was measured to determine amount of footprint
      restoration. RESULTS: For fixation strength, the mean peak load was significantly
      greater in the native tendon (1816 +/- 706 N) versus UBF/No. 5 suture/suture tape
      (794 +/- 168 N), UBF/suture tape (502 +/- 201 N), and bone trough (492 +/- 151 N)
      ( P < .001 for all). UBF/No. 5 suture/suture tape featured the lowest
      displacement superiorly (1.09 +/- 0.47 mm) and inferiorly (1.14 +/- 0.39 mm) with
      a significant difference compared with bone trough. With regard to tendon
      footprint reapproximation, cortical button fixation best approximated native
      tendon footprint length versus bone trough. CONCLUSION: Based on peak failure
      load, the UBF/No. 5 suture/suture tape construct demonstrated 61% greater
      construct strength than a traditional bone trough technique. Moreover,
      displacement after cyclic loading was by far smallest in the UBF/No. 5
      suture/suture tape construct. Therefore, repair constructs with larger caliber
      suture and suture tape provide a measurable improvement in construct strength
      versus traditional PM repair techniques in a biomechanical model and may be
      advantageous for repair. CLINICAL RELEVANCE: Cortical button fixation with larger
      caliber suture and suture tape allows for a significantly better PM repair than
      more traditional techniques at the time of surgery, which may ultimately result
      in improved clinical outcomes if implemented in surgical practice.

PMID- 28749742
TI  - Computed Tomographic Evaluation of Posttreatment Soft-Tissue Changes by Using a
      Lymphedema Scoring System in Patients with Oral Cancer.
AB  - BACKGROUND: This study aimed to evaluate posttreatment soft-tissue changes in
      patients with oral cancer with computed tomography (CT). To accomplish that
      purpose, a scoring system was established, referring to the criteria of lower leg
      lymphedema (LE). METHODS AND RESULTS: One hundred and six necks in 95 patients
      who underwent oral oncologic surgery with neck dissection (ND) were analyzed
      retrospectively using routine follow-up CT images. A two-point scoring system to
      evaluate soft-tissue changes (so-called "LE score") was established as follows:
      Necks with a "honeycombing" appearance were assigned 1 point. Necks with "taller
      than wide" fat lobules were assigned 1 point. Necks with neither appearance were
      assigned 0 points. Comparisons between patients with LE score >=1 and LE score =
      0 at 6 months postoperatively were performed using the Fisher exact test for
      discrete variables and the Mann-Whitney U test for continuous variables.
      Univariate predictors associated with posttreatment changes (i.e., LE score >=1
      at 6 months postoperatively) were entered into a multivariate logistic regression
      analysis. Values of p < 0.05 were considered to indicate statistical
      significance. The occurrence of the posttreatment soft-tissue changes was 32%.
      Multivariate logistic regression analysis showed that postoperative radiation
      therapy (RT) and bilateral ND were potential risk factors of posttreatment soft
      tissue changes on CT images. CONCLUSIONS: Sequential evaluation of "honeycombing"
      and the "taller than wide" appearances on routine follow-up CT revealed the
      persistence of posttreatment soft-tissue changes in patients who underwent oral
      cancer treatment, and those potential risk factors were postoperative RT and
      bilateral ND.

PMID- 28749743
TI  - Opportunities for Studying the Hydrodynamic Context for Breast Cancer Cell Spread
      Through Lymph Flow.
AB  - The lymphatic system serves as the primary route for the metastatic spread of
      breast cancer cells (BCCs). A scarcity of information exists with regard to the
      advection of BCCs in lymph flow and a fundamental understanding of the response
      of BCCs to the forces in the lymphatics needs to be established. This review
      summarizes the flow environment metastatic BCCs are exposed to in the lymphatics.
      Special attention is paid to the behavior of cells/particles in microflows in an
      attempt to elucidate the behavior of BCCs under lymph flow conditions (Reynolds
      number <1).

PMID- 28749744
TI  - Investigating the Short-Term Effects of Manual Lymphatic Drainage and Compression
      Garment Therapies on Lymphatic Function Using Near-Infrared Imaging.
AB  - BACKGROUND: Lymphedema is a chronic peripheral swelling caused by a dysfunction
      of the lymphatic system, leading to discomfort and loss of upper limb movement.
      Therapies to treat or manage this swelling have limited evidence, partly because
      of a paucity in objective lymphatic measures. This study explored the role of
      near-infrared (NIR) imaging in evaluating interventions. METHODS: Nine healthy
      volunteers underwent NIR fluoroscopy using a microdose (50 MUL, 0.05% w/v) of
      indocyanine green to quantify lymphatic behavior before and after a 15-minute
      period of manual lymph drainage followed by compression garment (CG) therapy for
      a 10-minute period. Images were taken at the forearm and elbow after each
      intervention. Lymphatic function was defined by the number, size, displacement,
      and speed of lymph packets. The lymph parameters were analyzed to assess the
      effects of the interventions compared with basal values. RESULTS: Baseline (BL)
      parameters of lymph function revealed high variability in the number, size, and
      speed of packets between individuals. Despite this variance, both interventions
      showed statistically significant improvement (p < 0.05) in displacement and speed
      at the forearm compared with BL. The velocity of transient lymph packets
      increased from a median of 6.7 mm/s at BL to 13.3 mm/s after manual lymphatic
      drainage (MLD) and 10.5 mm/s after CG. CONCLUSION: Lymphatic activity increased
      significantly after MLD, with relative increases being maintained after a short
      time period of CG application. NIR fluoroscopy has the potential to both monitor
      lymph pathology and provide robust parameters in the assessment of interventions.

PMID- 28749745
TI  - Alcohol Storylines in Television Episodes: The Preventive Effect of Countering
      Epilogues.
AB  - This experimental study assessed whether alcohol television storylines impact
      youth drinking attitudes and intentions and whether corrective epilogues can
      potentially moderate this impact. Television episodes were professionally
      produced to depict heavy drinking leading to either positive or negative
      consequences. The pro- and anti-alcohol episodes were shown alone or with an
      epilogue where a main character discussed the deleterious effects of excessive
      drinking. Attitudes toward drinkers and drinking intentions were measured
      subsequently, along with reactions to the episode and demographic data, among
      participants aged 14-17 using an online study. Exposure to the pro-alcohol
      episode was related to more positive attitudes toward drinkers. Including an
      epilogue after a pro-alcohol episode was related to more negative viewers'
      attitudes toward drinkers and lower drinking intentions compared to a pro-alcohol
      episode with no epilogue. By contrast, including an epilogue after an anti
      alcohol episode was unrelated to attitudes toward drinkers or drinking
      intentions. Viewing a single television episode with a pro-alcohol message may
      lead to more positive attitudes toward drinkers. The finding that a brief
      epilogue may reduce the impact of the pro-alcohol storyline suggests easily
      implemented preventive strategies to counter the adverse impact of substance use
      portrayals in entertainment programming.

PMID- 28749746
TI  - The increasing relevance of biofilms in common dermatological conditions.
AB  - BACKGROUND: Biofilms are diverse groups of microorganisms encased in a self
      produced matrix that offers protection against unfavorable conditions and
      antibiotics. METHODS: We performed a literature search using the MEDLINE
      electronic database. Only original articles published in English were considered
      for review. RESULTS: Biofilms have been implicated in the pathogenesis of acne,
      eczema, hidradenitis suppurativa, onychomycosis, miliaria, and impetigo. Adverse
      dermal-filler reactions are also linked to biofilms. Strict aseptic technique and
      prophylactic antibiotics are recommended in order to avoid such complications.
      Finally, biofilms are implicated in wounds, mainly chronic and diabetic, where
      they impede healing and cause recurrent infections. Several novel anti-biofilm
      agents and wound debridement have been shown to be beneficial. CONCLUSIONS:
      Biofilms are a significant cause of disease with wide implications in the field
      of dermatology. Several novel treatments have been found to be effective against
      biofilms, depending on the underlying microbes and type of disease.

PMID- 28749747
TI  - Influence of temperature and humidity on the long-term storage of latex and non
      latex orthodontic elastics.
AB  - OBJECTIVES: The objective of this study was to evaluate the influence of long
      term storage on latex and non-latex orthodontic elastics. MATERIALS AND METHODS:
      The sample consisted of 300 orthodontic elastics, 150 latex and 150 non-latex
      (American Orthodontics(r) *(AO) and Morelli(r)) of medium force and a standard
      size of 3/16'' divided into 20 groups, 10 for each manufacturer, with 15
      specimens each. The groups (G1*-G10* and G1-G10) were made up based on the
      manufacturer, storage temperature (ambient and refrigerated), material, and
      ambient humidity (exposed and non-exposed). The elastics were stretched and their
      forces measured in five progressive increases of 100% of their inner diameter,
      starting at a level of 200% stretching, by the MESDAN LAB 3000(r) (MESDAN, Italy)
      testing machine. The tests were carried out at two different times: immediately
      in as-received state and again after 1 year. Data were analysed using SPSS 16.0
      software, the Student's t-test, one-way analysis of variance (ANOVA) and the
      Tukey's post-test. RESULTS: There was a statistically significant difference
      between the average forces exerted by the latex elastics compared to the non
      latex elastics for all distention levels evaluated, except for 300%; however, the
      different storage conditions of temperature and humidity did not interfere in the
      mechanical properties. CONCLUSION: Both the latex and non-latex elastics may be
      stored under any of the conditions tested in the present study, since there were
      no changes in the potential of the force exerted by the elastics in relation to
      their percentage stretch over a 1-year period.

PMID- 28749748
TI  - Patterns of Health Information Technology Use according to Sexual Orientation
      among US Adults Aged 50 and Older: Findings from a National Representative Sample
      National Health Interview Survey 2013-2014.
AB  - Health disparities among sexual minority adults ages 50 and older have been
      documented. Factors such as lifetime discrimination and internalized stigma may
      deter sexual minority individuals from seeking health services. Several studies
      suggest that health information technology may facilitate health education and
      outreach to populations whose health behaviors are affected by stigma such as
      older sexual minority people. This study examined the role of sexual minority
      identity as a factor that is associated with health information technology use.
      Data from the 2013-2014 National Health Interview Survey (NHIS) were analyzed.
      Multivariate logistic regressions were used to compare the odds of using
      technology as a resource for health information between sexual minority versus
      heterosexual US adults aged 50 and older. Adjusting for sociodemographic
      variables and health variables, sexual minority participants had increased odds
      of using computers to look up health information on the Internet (OR = 2.01, 95%
      CI 1.53-2.64), using computers to fill a prescription (OR = 1.97, 95% CI 1.36
      2.85), and using computers to communicate with health-care provider by e-mail (OR
      = 2.13, 95% CI 1.55-2.92), compared with heterosexuals. Findings reveal greater
      use of health information technology among older sexual minority adults when
      compared to their heterosexual counterparts. While sensitive, competent providers
      and culturally appropriate prevention services are essential to meeting the needs
      of aging sexual minority populations, health information technology use may be an
      innovative means of reducing disparities in information access as structural
      changes are implemented.

PMID- 28749749
TI  - Estimation of Resting Energy Expenditure: Validation of Previous and New
      Predictive Equations in Obese Children and Adolescents.
AB  - OBJECTIVE: Accurate estimation of resting energy expenditure (REE) in childrenand
      adolescents is important to establish estimated energy requirements. The aim of
      the present study was to measure REE in obese children and adolescents by
      indirect calorimetry method, compare these values with REE values estimated by
      equations, and develop the most appropriate equation for this group. METHODS: One
      hundred and three obese children and adolescents (57 males, 46 females) between 7
      and 17 years (10.6 +/- 2.19 years) were recruited for the study. REE measurements
      of subjects were made with indirect calorimetry (COSMED, FitMatePro, Rome, Italy)
      and body compositions were analyzed. RESULTS: In females, the percentage of
      accurate prediction varied from 32.6 (World Health Organization [WHO]) to 43.5
      (Molnar and Lazzer). The bias for equations was -0.2% (Kim), 3.7% (Molnar), and
      22.6% (Derumeaux-Burel). Kim's (266 kcal/d), Schmelzle's (267 kcal/d), and
      Henry's equations (268 kcal/d) had the lowest root mean square error (RMSE;
      respectively 266, 267, 268 kcal/d). The equation that has the highest RMSE values
      among female subjects was the Derumeaux-Burel equation (394 kcal/d). In males,
      when the Institute of Medicine (IOM) had the lowest accurate prediction value
      (12.3%), the highest values were found using Schmelzle's (42.1%), Henry's
      (43.9%), and Muller's equations (fat-free mass, FFM; 45.6%). When Kim and Muller
      had the smallest bias (-0.6%, 9.9%), Schmelzle's equation had the smallest RMSE
      (331 kcal/d). The new specific equation based on FFM was generated as follows:
      REE = 451.722 + (23.202 * FFM). According to Bland-Altman plots, it has been
      found out that the new equations are distributed randomly in both males and
      females. CONCLUSION: Previously developed predictive equations mostly provided
      unaccurate and biased estimates of REE. However, the new predictive equations
      allow clinicians to estimate REE in an obese children and adolescents with
      sufficient and acceptable accuracy.

PMID- 28749750
TI  - Microbial Offense vs Host Defense: Who Controls the TB Granuloma?
AB  - The granuloma is the hallmark of tuberculosis and simultaneously signifies
      acquisition of an infection and induction of a host immune response. But who
      benefits more from the development of the granuloma, the host or the pathogen? Is
      microbe or man dictating disease course and progression? Mycobacterial diseases
      affect humans and animals alike, and the concepts presented in this review
      reflect host-pathogen interactions that influence not only mycobacterial
      granulomas in humans and animals but also other infectious granulomatous diseases
      that are encountered in veterinary medicine. Current dogma supports that an
      organized granuloma is a mark of an adequate and "restrictive" host immune
      response. However, the formation of a granuloma also provides a niche for the
      maturation, growth, and persistence of numerous infectious agents, and these
      pathogens devote some portion of their genetic machinery to ensuring these
      structures' form. An understanding of pathogens' contributions to granuloma
      formation can aid the development of host-directed therapies and other
      antimicrobial and antiparasitic therapies that can tip this balance in favor of a
      restrictive host response and elimination-not just containment-of the infectious
      organism. This review discusses animal models that have aided our understanding
      of pathogens' contribution to the host response and how mycobacterial virulence
      genes direct host pathology in ways that may aid disease transmission and/or
      persistence in the form of latent infection.

PMID- 28749751
TI  - The relationship between segmental kinematics and ball spin in Type-2 cricket
      spin bowling.
AB  - The techniques of spin bowling in cricket have been largely formulated from the
      collective intuitions of past players. A standard model of bowling technique has
      been generally prescribed for both off-spin and leg-spin bowlers, but there has
      been no biomechanics research to validate this approach. This study measured 20
      Type-2 off-spin and 15 Type-2 leg-spin bowlers using a 3D Cortex motion analysis
      system. Correlation coefficients between segmental kinematic variables and spin
      rate in the off-spin and leg-spin bowlers revealed that off-spin bowling was
      associated with an earlier movement time of the thorax, whereas leg-spin bowling
      was associated with a greater magnitude and earlier movement time of pelvis
      rotation, as well as a greater magnitude of pelvis-shoulder separation movement.
      The maximum velocity of rear hip flexion differentiated between both groups of
      bowlers. The GLM suggested that for off-spinners, rear hip flexion velocity
      significantly explained the variance in spin rate (subject to sequential timing
      constraints), while for leg-spinners, the time of maximum rear hip flexion and
      maximum arm circumduction velocity significantly explained variance in spin rate.
      This study supports the notion that off-spinners and leg-spinners have
      significant differences in their joint kinematics, and should not be coached
      under a one-size-fits-all technical model.

PMID- 28749752
TI  - High anion gap metabolic acidosis induced by cumulation of ketones, L- and D
      lactate, 5-oxoproline and acute renal failure.
AB  - INTRODUCTION: Frequent causes of high anion gap metabolic acidosis (HAGMA) are
      lactic acidosis, ketoacidosis and impaired renal function. In this case report, a
      HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5
      oxoproline is discussed. CASE PRESENTATION: A 69-year-old woman was admitted to
      the emergency department with lowered consciousness, hyperventilation, diarrhoea
      and vomiting. The patient had suffered uncontrolled type 2 diabetes mellitus,
      underwent gastric bypass surgery in the past and was chronically treated with
      high doses of paracetamol and fosfomycin. Urosepsis was diagnosed, whilst
      laboratory analysis of serum bicarbonate concentration and calculation of the
      anion gap indicated a  HAGMA. L-lactate, D-lactate, beta-hydroxybutyric acid,
      acetone and 5-oxoproline serum levels were markedly elevated and renal function
      was impaired. DISCUSSION: We concluded that this case of HAGMA was induced by a
      variety of underlying conditions: sepsis, hyperglycaemia, prior gastric bypass
      surgery, decreased renal perfusion and paracetamol intake. Risk factors for 5
      oxoproline intoxication present in this case are female gender, sepsis, impaired
      renal function and uncontrolled type 2 diabetes mellitus. Furthermore, chronic
      antibiotic treatment with fosfomycin might have played a role in the increased
      production of 5-oxoproline. CONCLUSION: Paracetamol-induced 5-oxoproline
      intoxication should be considered as a cause of HAGMA in patients with female
      gender, sepsis, impaired renal function or uncontrolled type 2 diabetes mellitus,
      even when other more obvious causes of HAGMA such as lactate, ketones or renal
      failure can be identified.

PMID- 28749756
TI  - Efficacy of Different Primaquine Regimens to Control Plasmodium falciparum
      Gametocytemia in Colombia.
AB  - Treatment against Plasmodium falciparum malaria includes blood schizonticides to
      clear asexual parasites responsible for disease. The addition of gametocytocidal
      drugs can eliminate infectious sexual stages with potential for transmission and
      the World Health Organization recommends a single dose (SD) of primaquine (PQ) to
      this end. The efficacy of PQ at 0.75 mg/kg to suppress gametocytemia when
      administered in single or fractionated doses was evaluated. A clinical controlled
      study with an open-label design was executed; three groups of 20 subjects were
      studied sequentially. All subjects were treated with the standard dose of
      artemether-lumefantrine plus the total dose of 0.75 mg/kg of PQ administered
      (without previous G6PD testing) in three different ways: Group "0.75d-3" received
      0.75 mg/kg on day 3; Group "0.50d-1 + 0.25d-3" received 0.50 mg/kg on day 1 and
      0.25 mg/kg on day 3; Group "0.25d-1,2,3" received 0.25 mg/kg on days 1, 2, and 3.
      Subjects were evaluated on days 1, 4, and 7 by thick smear microscopy and
      quantitative polymerase chain reaction to determine the carriage of immature and
      mature gametocytes. There were no adverse events. The three schemes caused a
      marked reduction (75-85%) in prevalence of gametocytes on day 4 compared with day
      1, but only the group that received 0.75 mg/kg on day 3 maintained the reduced
      gametocyte burden until day 7. None of the three treatments were able to clear
      gametocyte carriage on days 4 or 7, but the group that received the SD had the
      lowest prevalence of gametocytes (15%). Further studies are needed to establish a
      PQ regimen with complete efficacy against gametocytes.

PMID- 28749757
TI  - Paracoccidioidomycosis: Epidemiological and Clinical Aspects in 546 Cases Studied
      in the State of Espirito Santo, Brazil.
AB  - Paracoccidioidomycosis (PCM) is an endemic disease in the southeast region of
      Brazil, which includes the state of Espirito Santo (ES). This historic case
      series analyses 546 patients treated in this state from 1978 to 2012. Patients
      aged from 7 to 83 years, 509 males and 37 females, yielding a ratio of 13.7:1.
      Most of the patients (81.4%) originated from rural areas in ES, 71.0% being
      farmers. A higher concentration of cases was observed in municipalities located
      along the western range of the state. Sixty patients (11.0%) had an
      acute/subacute form of the disease, 485 (88.9%) had a chronic form, and one had a
      subclinical form. The most affected organs included the lungs, oropharyngeal
      mucosa, lymph nodes, skin, and larynx. The diagnosis was confirmed by
      histopathology in 252 (46.2%) cases, direct examination in 168 (30.7%), both
      exams in 111 (20.3%) and serology in 15 (2.8%). Tuberculosis, acquired immune
      deficiency syndrome, leishmaniasis, and intestinal parasites were the most
      frequently associated infectious diseases. From 328 patients followed up, total
      regression of the lesions was observed in 17.4%, partial regression in 77.4%, and
      no regression in 17 (5.2%) cases. Regarding the number of cases in this series,
      ES emerges as an important endemic area for PCM in Brazil.

PMID- 28749758
TI  - Identifying Helminth Infections via Routine Fecal Parasitological Examinations in
      Korea.
AB  - We conducted this study to explore the extent of occult helminth infection
      identified by fecal parasitological examinations or organ-specific examinations
      such as colonoscopy and abdominal ultrasonography (US) during health checkups. We
      analyzed 197,422 fecal samples from 99,451 subjects who received health checkups
      at a single center over 10 years. We found that 3,472 (1.8%) samples from 3,342
      (3.4%) subjects tested positive for parasitic ova, including clonorchiasis,
      metagonimiasis, trichuriasis, ascariasis, trichostrongylosis, taeniasis, and
      enterobiasis. The detection rate for clonorchiasis was higher in those who were
      taking their first examination than in those who had been examined previously.
      The detection rate for clonorchiasis decreased gradually over the 10 years. Only
      2.5% of the patients with clonorchiasis showed US or computed tomography (CT)
      images that were compatible with the disease. Clonorchiasis patients who had
      abdominal US or CT images that suggested clonorchiasis were older and had lower
      body mass indices and higher eosinophil counts than did those whose US or CT
      images did not suggest the disease. We observed worms in 9% of the patients with
      trichuriasis who had received a colonoscopy. Colonoscopy also uncovered adult
      worms in 0.03% of subjects who were not identified as having Trichuris trichiura
      ova in their fecal helminth examinations. In summary, our study shows that occult
      helminth infection is fairly frequently identified by a variety of methods during
      health checkups, which suggests that doctors need to make greater effort to
      identify and treat occult helminth infections in Korea.

PMID- 28749759
TI  - Criteria to Stop Mass Drug Administration for Lymphatic Filariasis Have Been
      Achieved Throughout Plateau and Nasarawa States, Nigeria.
AB  - Nigeria has the largest population at risk for lymphatic filariasis (LF) in
      Africa. This study used a transmission assessment survey (TAS) to determine
      whether mass drug administration (MDA) for LF could stop in 21 districts, divided
      into four evaluation units (EUs), of Plateau and Nasarawa States, Nigeria, after
      8-12 years of annual albendazole-ivermectin treatment. A total of 7,131 first-
      and second-year primary school children (approximately 6-7 years old) were tested
      for LF antigen by immunochromatographic test (ICT) from May to June 2012. The
      target sample size of 1,692 was exceeded in each EU (range = 1,767-1,795). A
      total of 25 (0.4%) individuals were ICT positive, with the number of positives in
      each EU (range = 3-11) less than the TAS cutoff of 20, meaning that LF
      transmission had been reduced below sustainable levels. As a result, 3.5 million
      annual albendazole-ivermectin treatments were halted in 2013. Combined with the
      previous halt of MDA for LF in other parts of Plateau and Nasarawa, these are the
      first Nigerian states to stop LF MDA statewide. Posttreatment surveillance is
      ongoing to determine if LF transmission has been interrupted.

PMID- 28749760
TI  - Evaluating Human Sensory Perceptions and the Compartment Bag Test Assays as
      Proxies for the Presence and Concentration of Escherichia coli in Drinking Water
      in Western Kenya.
AB  - We compared the concentrations of Escherichia coli quantified with ColilertTM and
      the compartment bag test (CBT) in the source water and household stored drinking
      water (SDW) of 35 households in western Kenya. We also investigated the
      associations of the perceptions of organoleptic properties and overall quality
      with >= 1 MPN/100 mL E. coli in SDW. Participants who rated the taste or smell of
      their SDW "< 5" on a 1 = "poor" to 5 = "excellent" Likert scale were 8.71 or 7.04
      times more likely, respectively, to have >= 1 MPN/100 mL E. coli. Organoleptic
      properties are innate, albeit imperfect, indicators of fecal pollution in water.
      Within their shared quantification range, concentrations of E. coli enumerated
      with Colilert and CBT were similar and had a significant correlation coefficient,
      0.896 (95% confidence interval = 0.691-1.101). The methods had moderate agreement
      within the World Health Organization's health risk levels (Cohen's Kappa
      coefficient = 0.640). In low-resource settings, CBT provides comparable
      assessments of E. coli concentrations to Colilert.

PMID- 28749761
TI  - Molecular Characterization of a Cluster of Imported Malaria Cases in Puerto Rico.
AB  - The Caribbean island of Hispaniola is targeted for malaria elimination.
      Currently, this is the only island with ongoing transmission of malaria in the
      Caribbean. In 2015, six patients from Puerto Rico and one from Massachusetts, who
      traveled to Punta Cana, Dominican Republic, were confirmed to be infected with
      Plasmodium falciparum. Additional molecular analysis was performed at the Centers
      for Disease Control and Prevention to characterize the drug-resistant alleles and
      Plasmodium population genetic markers. All specimens carried wildtype genotypes
      for chloroquine, sulfadoxine-pyrimethamine, and artemisinin resistance genetic
      markers. A mutation in codon 184 (Y/F) of Pfmdr-1 gene was observed in all
      samples and they shared an identical genetic lineage as determined by
      microsatellite analysis. This genetic profile was similar to one previously
      reported from Hispaniola suggesting that a clonal P. falciparum residual parasite
      population present in Punta Cana is the source population for these imported
      malaria cases.

PMID- 28749762
TI  - Efficacy of Artesunate/Amodiaquine in the Treatment of Uncomplicated Malaria
      among Children in Ghana.
AB  - The declining efficacy of chloroquine in the early 2000s in Ghana led to its
      replacement with artesunate/amodiaquine (AS/AQ) combination as first-line drug
      for treating uncomplicated malaria in 2005. Since then efficacy studies have been
      ongoing in the country to provide continuous data on the efficacy of AS/AQ and
      other alternative antimalarials (artemether/lumefantrine and
      dihyroartemisinin/piperaquine combinations) introduced in 2008. In vivo AS/AQ
      efficacy studies were conducted between June and October 2014 among children aged
      6 months to 14 years, in two sentinel sites representing the forest and coastal
      zones of the country. The 2009 World Health Organization protocol for monitoring
      antimalarial drug efficacy was used in these studies. The studies showed an
      overall cumulative polymerase chain reaction-corrected day 28 cure rate of 97.2%
      (95% confidence interval [CI]: 93.6-99.1): 97.7% (95% CI: 92.0-99.7) within the
      forest zone and 96.7% (95% CI: 90.7-99.3) within the coastal zone (P = 0.686).
      Prevalence of fever declined from 100% to < 4% after first day of treatment in
      both ecological zones. All children in the coastal zone had cleared parasites by
      day 2. Three children (3.2%) in the forest zone were parasitemic on day 2,
      whereas one child was parasitemic on day 3. Gametocytemia was absent in both
      zones after day 14, and mean hemoglobin concentration significantly increased
      from 10.3 g/dL (95% CI: 10.1-10.5) on day 0 to 11.8 g/dL (95% CI: 11.6-12.0) on
      day 28. We conclude that AS/AQ combination remains efficacious in the treatment
      of uncomplicated malaria in Ghana.

PMID- 28749763
TI  - Outbreak of Sudden Death with Acute Encephalitis Syndrome Among Children
      Associated with Exposure to Lychee Orchards in Northern Bangladesh, 2012.
AB  - Recurrent outbreaks of acute encephalitis syndrome (AES) among children in lychee
      growing areas in Asia highlight the need to better understand the etiology and
      the context. We conducted a mixed-methods study to identify risk factors for
      disease, and behaviors and practices around lychee cultivation in an AES outbreak
      community in northern Bangladesh in 2012. The outbreak affected 14 children; 13
      died. The major symptoms included unconsciousness, convulsion, excessive
      sweating, and frothy discharge. The median time from illness onset to
      unconsciousness was 2.5 hours. The outbreak corresponded with lychee harvesting
      season. Multiple pesticides including some banned in Bangladesh were frequently
      used in the orchards. Visiting a lychee orchard within 24 hours before onset (age
      adjusted odds ratio [aOR] = 11.6 [1.02-109.8]) and 3 days (aOR = 7.2 [1.4-37.6]),
      and family members working in a lychee orchard (aOR = 7.2 [1.7-29.4]) and
      visiting any garden while pesticides were being applied (aOR = 4.9 [1.0-19.4]) in
      3 days preceding illness onset were associated with illness in nearby village
      analysis. In neighborhood analysis, visiting an orchard that used pesticides (aOR
      = 8.4 [1.4-49.9]) within 3 days preceding illness onset was associated with
      illness. Eating lychees was not associated with illness in the case-control
      study. The outbreak was linked to lychee orchard exposures where agrochemicals
      were routinely used, but not to consumption of lychees. Lack of acute specimens
      was a major limitation. Future studies should target collection of environmental
      and food samples, acute specimens, and rigorous assessment of community use of
      pesticides to determine etiology.

PMID- 28749764
TI  - Use of Serologic Responses against Enteropathogens to Assess the Impact of a
      Point-of-Use Water Filter: A Randomized Controlled Trial in Western Province,
      Rwanda.
AB  - Diarrhea is a leading contributor to childhood morbidity and mortality in sub
      Saharan Africa. Given the challenge of blinding most water, sanitation, and
      hygiene (WASH) interventions, diarrheal disease outcome measures in WASH
      intervention trials are subject to potential bias and misclassification. Using
      the platform of a cluster-randomized controlled trial of a household-based
      drinking water filter in western province, Rwanda, we assessed the impact of the
      drinking water filter on enteric seroconversion in young children as a health
      outcome and examined the association between serologic responses and caregiver
      reported diarrhea. Among the 2,179 children enrolled in the trial, 189 children 6
      12 months of age were enrolled in a nested serology study. These children had
      their blood drawn at baseline and 6-12 months after the intervention was
      distributed. Multiplex serologic assays for Giardia, Cryptosporidium, Entamoeba
      histolytica, norovirus, Campylobacter, enterotoxigenic Escherichia coli and
      Vibrio cholerae were performed. Despite imperfect uptake, receipt of the water
      filter was associated with a significant decrease in seroprevalence of IgG
      directed against Cryptosporidium parvum Cp17 and Cp23 (relative risk [RR]: 0.62,
      95% confidence interval [CI]: 0.44-0.89). Serologic responses were positively
      associated with reported diarrhea in the previous 7 days for both Giardia
      intestinalis (RR: 1.94, 95% CI: 1.04-3.63) and C. parvum (RR: 2.21, 95% CI: 1.09
      4.50). Serologic responses for all antigens generally increased in the follow-up
      round, rising sharply after 12 months of age. The water filter is associated with
      reduced serologic responses against C. parvum, a proxy for exposure and
      infection; therefore, serologic responses against protozoa may be a suitable
      health outcome measure for WASH trials among children with diarrhea.

PMID- 28749765
TI  - Generation and Characterization of Antinonstructural Protein 1 Monoclonal
      Antibodies and Development of Diagnostics for Dengue Virus Serotype 2.
AB  - Dengue virus (DENV) circulates in tropical and subtropical areas around the
      world, where it causes high morbidity and mortality. There is no effective
      treatment of infection, with supportive care being the only option. Furthermore,
      early detection and diagnosis are important to facilitate clinical decisions. In
      this study, seven monoclonal antibodies (mAbs) recognizing nonstructural protein
      1 (NS1) of DENV were generated by hybridoma techniques. These antibodies can be
      divided into two groups: serotype-specific (DB6-1, DB12-3, and DB38-1) and
      nonspecific (consisting of antibodies DB16-1, DB20-6, DB29-1, and DB41-2). The B
      cell epitopes of DB20-6 and DB29-1 were identified by phage display and site
      directed mutagenesis, and its binding motif, WXXWGK, was revealed to correspond
      to amino acid residues 115-120 of the DENV-2 NS1 protein. A diagnostic platform,
      consisting of a serotype-specific capture antibody and a complex detection
      antibody, exhibited a detection limit of about 1 ng/mL, which is sufficient to
      detect NS1 in clinical serum samples from dengue patients. This diagnostic
      platform displayed better specificity and sensitivity than two examined
      commercial NS1 diagnostic platforms. In summary, our results indicate that these
      newly generated mAbs are suitable for detection of NS1 protein of DENV-2 in
      clinical samples.

PMID- 28749766
TI  - Identifying Potential Sources of Exposure Along the Child Feces Management
      Pathway: A Cross-Sectional Study Among Urban Slums in Odisha, India.
AB  - Child feces represent a particular health risk to children due to increased
      prevalence of enteric agents and a higher risk of exposure owing to exploratory
      behaviors of young children. The safe management of such feces presents a
      significant challenge, not only for the 2.4 billion who lack access to improved
      sanitation, but also due to unhygienic feces collection and disposal and poor
      subsequent handwashing practices. We assessed potential sources of fecal exposure
      by documenting child feces management practices in a cross-sectional study of 851
      children < 5 years of age from 694 households in 42 slums in two cities in
      Odisha, India. No preambulatory children and only 27.4% of ambulatory children
      defecated directly in the latrine. Children that did not defecate in a latrine
      mainly defecated on the ground, whether they were preambulatory or ambulatory.
      Use of diapers (1.2%) or potties (2.8%) was low. If the feces were removed from
      the ground, the defecation area was usually cleaned, if at all, only with water.
      Most children's feces were disposed of in surrounding environment, with only 6.5%
      deposited into any kind of latrine, including unimproved. Handwashing with soap
      of the caregiver after child feces disposal and child anal cleaning with soap
      after defecation was also uncommon. While proper disposal of child feces in an
      improved latrine still represents a major challenge, control of the risks
      presented requires attention to the full range of exposures associated to the
      management of child feces, and not simply the place of disposal.

PMID- 28749767
TI  - Case Report: Successful Lung Transplantation from a Donor Seropositive for
      Trypanosoma cruzi Infection (Chagas Disease) to a Seronegative Recipient.
AB  - The increasing shortage of organs for transplantation has prompted transplant
      programs to investigate the use of extended criteria donors, such as those with
      transmissible infectious diseases. Successful cases of organ transplantation
      (mostly kidney and liver) from Trypanosoma cruzi seropositive donors to
      seronegative recipients have been reported. We present a case of lung
      transplantation from a donor serologically positive for Chagas disease to a
      seronegative recipient, and provide a review of the literature. Left single lung
      transplantation was performed in a 44-year-old Spanish woman presenting with
      interstitial lung disease in February 2016. The deceased donor was a Colombian
      immigrant living in Spain who was serologically positive for Chagas disease. Oral
      administration of 5 mg/kg/day benznidazole divided in three doses for 60 days was
      given for specific Chagas disease prophylaxis after transplantation. Periodic
      follow-up with serological reverse transcription polymerase chain reaction to
      detect T. cruzi DNA were performed until 6 months after the end of treatment. All
      results were negative, indicating that transmission of T. cruzi had not occurred.
      In a review of the literature, two similar cases were identified in Argentina and
      the United States. In both cases T. cruzi infection was detected posttransplant
      in the recipients, after which they were treated with benznidazole. The course of
      the patient described herein confirms that lungs from donors with chronic T.
      cruzi infection can be used successfully as allografts, and that posttransplant
      prophylaxis with benznidazole may reduce the probability of transmission of T.
      cruzi to the recipient.

PMID- 28749768
TI  - Evidence-Based Guidelines for Screening and Management of Strongyloidiasis in Non
      Endemic Countries.
AB  - Strongyloidiasis is an intestinal parasitic infection becoming increasingly
      important outside endemic areas, not only because of the high prevalence found in
      migrant populations, but also because immunosuppressed patients may suffer a
      potentially fatal disseminated disease. The aim of these guidelines is to provide
      evidence-based guidance for screening and treatment of strongyloidiasis in non
      endemic areas. A panel of experts focused on three main clinical questions (who
      should be screened and how, how to treat), and reviewed pertinent literature
      available in international databases of medical literature and in documents
      released by relevant organizations/societies. A consensus of the experts' opinion
      was sought when specific issues were not covered by evidence. In particular, six
      systematic reviews were retrieved and constituted the main support for this work.
      The evidence and consensus gathered led to recommendations addressing various
      aspects of the main questions. Grading of evidence and strength of recommendation
      were attributed to assess the quality of supporting evidence. The screening of
      individuals at risk of the infection should be performed before they develop any
      clinical complication. Moreover, in immunosuppressed patients, the screening
      should be mandatory. The screening is based on a simple and widely accessible
      technology and there is now a universally accepted treatment with a high efficacy
      rate. Therefore, the screening could be implemented as part of a screening
      program for migrants although further cost-effectiveness studies are required to
      better evaluate this strategy from a public health point of view.

PMID- 28749769
TI  - A Systematic Review and Meta-Analysis of Practices Exposing Humans to Avian
      Influenza Viruses, Their Prevalence, and Rationale.
AB  - Almost all human infections by avian influenza viruses (AIVs) are transmitted
      from poultry. A systematic review was conducted to identify practices associated
      with human infections, their prevalence, and rationale. Observational studies
      were identified through database searches. Meta-analysis produced combined odds
      ratio estimates. The prevalence of practices and rationales for their adoptions
      were reported. Of the 48,217 records initially identified, 65 articles were
      included. Direct and indirect exposures to poultry were associated with infection
      for all investigated viral subtypes and settings. For the most frequently
      reported practices, association with infection seemed stronger in markets than
      households, for sick and dead than healthy poultry, and for H7N9 than H5N1.
      Practices were often described in general terms and their frequency and intensity
      of contact were not provided. The prevalence of practices was highly variable
      across studies, and no studies comprehensively explored reasons behind the
      adoption of practices. Combining epidemiological and targeted anthropological
      studies would increase the spectrum and detail of practices that could be
      investigated and should aim to provide insights into the rationale(s) for their
      existence. A better understanding of these rationales may help to design more
      realistic and acceptable preventive public health measures and messages.

PMID- 28749770
TI  - In Silico Prediction of Antibiotic Resistance in Mycobacterium ulcerans Agy99
      through Whole Genome Sequence Analysis.
AB  - Buruli ulcer is an emerging infectious disease caused by Mycobacterium ulcerans
      that has been reported from 33 countries. Antimicrobial agents either alone or in
      combination with surgery have been proved to be clinically relevant and
      therapeutic strategies have been deduced mainly from the empirical experience.
      The genome sequences of M. ulcerans strain AGY99, M. ulcerans ecovar liflandii,
      and three Mycobacterium marinum strains were analyzed to predict resistance in
      these bacteria. Fourteen putative antibiotic resistance genes from different
      antibiotics classes were predicted in M. ulcerans and mutation in katG (R431G)
      and pncA (T47A, V125I) genes were detected, that confer resistance to isoniazid
      and pyrazinamide, respectively. No mutations were detected in rpoB, gyrA, gyrB,
      rpsL, rrs, emb, ethA, 23S ribosomal RNA genes and promoter region of inhA and
      ahpC genes associated with resistance. Our results reemphasize the usefulness of
      in silico analysis for the prediction of antibiotic resistance in fastidious
      bacteria.

PMID- 28749771
TI  - Seroprevalence of Brucellosis among Patients Attending a District Hospital in
      Rwanda.
AB  - Studies on human brucellosis in Rwanda are scarce, and the incidence is likely to
      be higher than official estimates. In a recent study using Rose Bengal Test (RBT)
      on women who had aborted or had still births in Huye district, 25% were Brucella
      seroprevalent. Thus, purpose of the present study was to investigate the Brucella
      seroprevalence in patients presenting with the key signs and symptoms of
      brucellosis. Cross-sectional study was done in Nyagatare District in the Eastern
      Province of Rwanda. A total of 198 patients were recruited from Nyagatare
      District Hospital, blood samples were collected, and sera analyzed with RBT. A
      questionnaire was used to explore the risk factors. A total of 12 patients (6.1%;
      95% confidence interval [CI] = 0.662-7.820) were Brucella seropositive. Infection
      was significantly associated with drinking unboiled milk (odds ratio [OR] = 8.3;
      95% CI = 2.4-29.2) and having had recurrent fever (OR = 5.6; 95% CI = 1.5-21.3).
      Drinking unboiled milk is a risk factor for Brucella infection. Provision of
      adequate resources and trainings to staff in brucellosis diagnosis is needed to
      reduce recurrence of fevers probably because of misdiagnosis. Public awareness
      creation on transmission routes of brucellosis is to be intensified.

PMID- 28749772
TI  - Plasmodium vivax Infections over 3 Years in Duffy Blood Group Negative Malians in
      Bandiagara, Mali.
AB  - Plasmodium vivax was thought to infect only the erythrocytes of Duffy blood group
      positive people. In the last decade, P. vivax has appeared throughout Africa,
      both in areas where Duffy positive and negative people live side by side as in
      Madagascar and Ethiopia and in areas where people are primarily Duffy negative,
      such as in western Kenya. We performed quantitative polymerase chain reaction on
      blood samples dried onto filter paper to determine the prevalence of P. vivax and
      Plasmodium falciparum in a cohort of 300 children (newborn to 6 years of age) in
      Bandiagara, a Sahelian area of Mali, west Africa, where the people are Duffy
      negative. We report 1-3 occurrences of P. vivax in each of 25 Duffy-negative
      children at six time points over two rainy seasons and the beginning of the third
      season. The prevalence of P. vivax infection was 2.0-2.5% at every time point
      (June 2009 to June 2010). All children with P. vivax infections were asymptomatic
      and afebrile, and parasite densities were extremely low. Anemia, however, was the
      main burden of infection. Plasmodium vivax could become a burden to sub-Saharan
      Africa, and the evidence of P. vivax existence needs to be taken into
      consideration in designing malaria control and elimination strategies in Africa.

PMID- 28749773
TI  - Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose
      6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PD Mahidol Variant) versus G6PD
      Normal Volunteers.
AB  - Tafenoquine is an 8-aminoquinoline under investigation for the prevention of
      relapse in Plasmodium vivax malaria. This open-label, dose-escalation study
      assessed quantitatively the hemolytic risk with tafenoquine in female healthy
      volunteers heterozygous for the Mahidol487A glucose-6-phosphate dehydrogenase
      (G6PD)-deficient variant versus G6PD-normal females, and with reference to
      primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40-60% of
      normal) and six G6PD-normal subjects per treatment group received single-dose
      tafenoquine (100, 200, or 300 mg) or primaquine (15 mg * 14 days). All
      participants had pretreatment hemoglobin levels >= 12.0 g/dL. Tafenoquine dose
      escalation stopped when hemoglobin decreased by >= 2.5 g/dL (or hematocrit
      decline >= 7.5%) versus pretreatment values in >= 3/6 subjects. A dose-response
      was evident in G6PD-heterozygous subjects (N = 15) receiving tafenoquine for the
      maximum decrease in hemoglobin versus pretreatment values. Hemoglobin declines
      were similar for tafenoquine 300 mg (-2.65 to -2.95 g/dL [N = 3]) and primaquine
      (-1.25 to -3.0 g/dL [N = 5]). Two further cohorts of G6PD-heterozygous subjects
      with G6PD enzyme levels 61-80% (N = 2) and > 80% (N = 5) of the site median
      normal received tafenoquine 200 mg; hemolysis was less pronounced at higher G6PD
      enzyme activities. Tafenoquine hemolytic potential was dose dependent, and
      hemolysis was greater in G6PD-heterozygous females with lower G6PD enzyme
      activity levels. Single-dose tafenoquine 300 mg did not appear to increase the
      severity of hemolysis versus primaquine 15 mg * 14 days.

PMID- 28749774
TI  - Assessment of Risk of Cholera in Haiti following Hurricane Matthew.
AB  - Damage to the inferior and fragile water and sanitation infrastructure of Haiti
      after Hurricane Matthew has created an urgent public health emergency in terms of
      likelihood of cholera occurring in the human population. Using satellite-derived
      data on precipitation, gridded air temperature, and hurricane path and with
      information on water and sanitation (WASH) infrastructure, we tracked changing
      environmental conditions conducive for growth of pathogenic vibrios. Based on
      these data, we predicted and validated the likelihood of cholera cases occurring
      past hurricane. The risk of cholera in the southwestern part of Haiti remained
      relatively high since November 2016 to the present. Findings of this study
      provide a contemporary process for monitoring ground conditions that can guide
      public health intervention to control cholera in human population by providing
      access to vaccines, safe WASH facilities. Assuming current social and behavioral
      patterns remain constant, it is recommended that WASH infrastructure should be
      improved and considered a priority especially before 2017 rainy season.

PMID- 28749775
TI  - Implementing a Quality Improvement Collaborative to Improve Hypertension Control
      and Advance Million Hearts Among Low-Income Californians, 2014-2015.
AB  - From January through December 2015, the California Department of Health Care
      Services, which administers Medi-Cal, the nation's largest Medicaid program,
      conducted a quality improvement collaborative (QIC) with 9 Medi-Cal managed care
      plans (MCPs) aimed at improving hypertension control consistent with the Million
      Hearts initiative. The QIC included quarterly webinars and links to local, state,
      and national resources that consisted of materials and consultations with subject
      matter experts. Participating MCPs demonstrated an average increase of 5.0
      percentage points in their rates of controlled hypertension. Collaboratives can
      achieve substantial quality improvement in Medicaid managed care plans.

PMID- 28749776
TI  - Comorbid Arthritis Is Associated With Lower Health-Related Quality of Life in
      Older Adults With Other Chronic Conditions, United States, 2013-2014.
AB  - INTRODUCTION: Arthritis is related to poor health-related quality of life (HRQoL)
      in adults aged 18 years or older. We sought to determine whether this
      relationship persisted in an older population using claims-based arthritis
      diagnoses and whether people who also had arthritis and at least 1 of 5 other
      chronic conditions had lower HRQoL. METHODS: We identified adults aged 65 years
      or older with Medicare Advantage coverage in November or December 2014 who
      responded to an HRQoL survey (Healthy Days). For respondents with and without
      arthritis, we used linear regression to compare mean physically, mentally, and
      total unhealthy days, overall and in 5 comorbidity subgroups (coronary artery
      disease, congestive heart failure, chronic obstructive pulmonary disease,
      diabetes, and hypertension), accounting for age, sex, dual Medicaid/Medicare
      eligibility, rural/urban commuting area, and Charlson Comorbidity Index. RESULTS:
      Of the 58,975 survey respondents, 44% had arthritis diagnosed through claims.
      Respondents with arthritis reported significantly more adjusted mean physically,
      mentally, and total unhealthy days than those without arthritis (P < .001). Older
      adults with arthritis and either congestive heart failure, chronic obstructive
      pulmonary disease, diabetes, or hypertension reported significantly more adjusted
      physically, mentally, and total unhealthy days than older adults without
      arthritis but with the same chronic conditions. CONCLUSIONS: In older adults,
      having arthritis is associated with lower HRQoL and even lower HRQoL among those
      with at least 1 of 5 other common chronic conditions. Because arthritis is so
      common among older adults, improving HRQoL depends on managing both underlying
      chronic conditions and any accompanying arthritis.

PMID- 28749777
TI  - Location Is Everything: The Pollutants in Yellowfin Tuna Depend on Where It's
      Caught.

PMID- 28749778
TI  - Serum Vaccine Antibody Concentrations in Adolescents Exposed to Perfluorinated
      Compounds.
AB  - BACKGROUND: Postnatal exposure to perfluorinated alkylate substances (PFASs) is
      associated with lower serum concentrations of specific antibodies against certain
      childhood vaccines at 7 y. OBJECTIVES: We prospectively followed a Faroese birth
      cohort to determine these associations at 13 y. METHODS: In 516 subjects (79% of
      eligible cohort members) who were 13 years old, serum concentrations of PFASs and
      of antibodies against diphtheria and tetanus were measured and were compared with
      data from the previous examination at 7 y. Multiple regression analyses and
      structural equation models were applied to determine the association between
      postnatal PFAS exposures and antibody concentrations. RESULTS: Serum
      concentrations of PFASs and antibodies generally declined from 7 y to 13 y.
      However, 68 subjects had visited the emergency room and had likely received a
      vaccination booster, and a total of 202 children showed higher vaccine antibody
      concentrations at 13 y than at 7 y. Therefore, separate analyses were conducted
      after exclusion of these two subgroups. Diphtheria antibody concentrations
      decreased at elevated PFAS concentrations at 13 y and 7 y; the associations were
      statistically significant for perfluorodecanoate (PFDA) at 7 y and for
      perfluorooctanoate (PFOA) at 13 y, both suggesting a decrease by ~25% for each
      doubling of exposure. Structural equation models showed that a doubling in PFAS
      exposure at 7 y was associated with losses in diphtheria antibody concentrations
      at 13 y of 10-30% for the five PFASs. Few associations were observed for anti
      tetanus concentrations. CONCLUSIONS: These results are in accord with previous
      findings of PFAS immunotoxicity at current exposure levels.
      https://doi.org/10.1289/EHP275.

PMID- 28749779
TI  - Weekly Personal Ozone Exposure and Respiratory Health in a Panel of Greek
      Schoolchildren.
AB  - BACKGROUND: The association of ozone exposure with respiratory outcomes has been
      investigated in epidemiologic studies mainly including asthmatic children. The
      findings reported had methodological gaps and inconsistencies. OBJECTIVES: We
      aimed to investigate effects of personal ozone exposure on various respiratory
      outcomes in school-age children generally representative of the population during
      their normal activities. METHODS: We conducted a panel study in a representative
      sample of school-age children in the two major cities of Greece, Athens and
      Thessaloniki. We followed 188, 10- to 11-y-old, elementary school students for 5
      wk spread throughout the 2013-2014 academic year, during which ozone was measured
      using personal samplers. At the end of each study week, spirometry was performed
      by trained physicians, and the fractional concentration of nitric oxide in
      exhaled air (FeNO) was measured. Students kept a daily time-activity-symptom
      diary and measured PEF (peak expiratory flow) using peak flow meters. Mixed
      models accounting for repeated measurements were applied. RESULTS: An increase of
      10 MUg/m3 in weekly ozone concentration was associated with a decrease in FVC
      (forced vital capacity) and FEV1 (forced expiratory volume in 1 s) of 0.03 L [95%
      confidence interval (CI): -0.05, -0.01] and 0.01 L (95% CI: -0.03, 0.003)
      respectively. The same increase in exposure was associated with a 11.10% (95% CI:
      4.23, 18.43) increase in FeNO and 19% (95% CI: -0.53, 42.75) increase in days
      with any symptom. The effect estimates were robust to PM10 adjustment. No inverse
      association was found between ozone exposure and PEF. CONCLUSIONS: The study
      provides evidence that airway inflammation and the frequency of respiratory
      symptoms increase, whereas lung function decreases with increased ozone exposure
      in schoolchildren. https://doi.org/10.1289/EHP635.

PMID- 28749781
TI  - Contested Practice: Political Activism in Nursing and Implications for Nursing
      Education.
AB  - Canadian nurses have a social mandate to address health inequities for the
      populations they serve, as well as to speak out on professional and broader
      social issues. Although Canadian nursing education supports the role of nurses as
      advocates for social justice and leadership for health care reform, little is
      known about how nurse educators understand activism and how this translates in
      the classroom. A comparative life history study using purposeful sampling and a
      critical feminist lens was undertaken to explore political activism in nursing
      and how nurse educators foster political practice among their students. Findings
      from interviews and focus groups with 26 Ontario nurse educators and nursing
      students suggested that neoliberal dynamics in both the practice setting and in
      higher education have constrained nurses' activist practice and favour a
      technical rational approach to nursing education. Implications and strategies to
      inspire political action in nursing education are discussed.

PMID- 28749780
TI  - The Prevalence of Extended-Spectrum Beta-Lactamase-Producing Multidrug-Resistant
      Escherichia Coli in Poultry Chickens and Variation According to Farming Practices
      in Punjab, India.
AB  - BACKGROUND: Agricultural use of antimicrobials in subtherapeutic concentrations
      is increasing in response to the rising demand for food animal products
      worldwide. In India, the use of antimicrobials in food animal production is
      unregulated. Research suggests that many clinically important antimicrobials are
      used indiscriminately. This is the largest study to date in India that surveys
      poultry production to test for antimicrobial resistance and the occurrence of
      extended-spectrum beta-lactamases (ESBLs) modulated by farming and managerial
      practices. OBJECTIVES: Our goal was to survey poultry production for resistance
      to eleven clinically relevant antimicrobials and phenotypic occurrence of ESBLs
      as modulated by farming and managerial practices. METHODS: Eighteen poultry farms
      from Punjab were surveyed, and 1,556 Escherichia coli isolates from 530 birds
      were tested for susceptibility to 11 antimicrobials using the disk diffusion
      method and validated using VITEK 2 (bioMerieux, Marcy-L'Etoile, France). Samples
      from 510 of these birds were phenotypically tested for ESBL production using the
      combination disk method and confirmed using VITEK 2. Generalized linear mixed
      models were used to infer differences in resistance profiles associated with
      different farming practices and facility types. RESULTS: Resistance profiles were
      significantly different between broiler and layer farms. Broiler farms were 2.2
      [ampicillin (AMP), p=0.017] to 23 [nalidixic acid (NX), p<0.001] times more
      likely to harbor resistant E. coli strains than layer farms. Adjusting for farm
      type (broiler vs. layer), the odds of resistance (although not statistically
      significant) to all antimicrobials except nitrofurantoin (NIT) were higher in
      independent facilities (IUs) as compared to contracted facilities (CFs).
      Increased prevalence of multidrug resistance (MDR; 94% compared to 60% in
      layers), including prevalence of ESBL-producing strains (87% compared to 42% in
      layers), was observed in broiler farms. CONCLUSIONS: Our findings suggest that
      unregulated use of clinically relevant antimicrobials in Indian broiler and layer
      farms may contribute to the emergence of resistance and support the need to curb
      the nontherapeutic use of medically important antimicrobials in food animal
      production. https://doi.org/10.1289/EHP292.

PMID- 28749782
TI  - Erection-stimulating, anti-diabetic and antioxidant properties of Hunteria
      umbellata and Cylicodiscus gabunensis water extractable phytochemicals.
AB  - Background Herbs have been used as an aphrodisiac since ages. This study was
      designed to investigate the effects of Hunteria umbellata (HU) seeds and
      Cylicodiscus gabunensis (CG) stem barks aqueous extracts on key enzymes relevant
      to erectile dysfunction (phosphodiesterase-5 and arginase) and type-2 diabetes
      (alpha-amylase and alpha-glucosidase). Methods In ascertaining the erectogenic
      and antidiabetic properties of the extracts, the effects of the extracts on
      activities of some enzymes relevant to erectile dysfunction (arginase and
      phosphodiesterase-5) and type-2 diabetes (alpha-amylase and alpha-glucosidase)
      were determined. Antioxidant properties of the extracts were assessed through
      several antioxidant assays (DPPH, OH). Furthermore, their phenolic constituents
      were estimated and quantified using HPLC. Results The results revealed that both
      extracts inhibited alpha-amylase and alpha-glucosidase in a concentration
      dependent manner. HU showed higher alpha-amylase (IC50=221.30 ug/mL) and alpha
      glucosidase (IC50=184.35 ug/mL) inhibition than CG. Also, both extracts inhibited
      phosphodiesterase-5 and arginase in a dose-dependent manner in vitro;
      nevertheless, HU showed higher inhibition [phosphodiesterase-5 (IC50=539.72
      ug/mL); arginase (41.53 ug/mL)] than CG [phosphodiesterase-5 (IC50=611.35 ug/mL);
      arginase (47.95 ug/mL)]. In addition, the extracts possess antioxidant properties
      through radical (DPPH and OH) scavenging and metal (Fe2+) chelating abilities.
      HPLC analysis of phenolic constituents revealed the abundance of gallic acid,
      chlorogenic acid, caffeic acid, ellagic acid and quercetin. Conclusions The
      ability of samples' extract to inhibit some of key enzymes relevant to erectile
      dysfunction and type-2 diabetes could render them cheap, natural and alternative
      therapy with erectogenic and antidiabetic potentials.

PMID- 28749783
TI  - Multinodular goiter in children: treatment controversies.
AB  - BACKGROUND: Multinodular goiter (MG) is very common in adults. MG may occur in
      children in some exceptional circumstances. The objective of this study was to
      examine two cases of MG in children who relapsed soon after surgery and to
      discuss the treatment options in pediatric ages. METHODS: Two girls consulted for
      euthyroid colloid goiter, uninodular goiter and bilateral MG. They were
      intervened by hemithyroidectomy and total thyroidectomy, respectively, due to the
      existence of local symptoms. RESULTS: Goiters reappeared 3 years after
      intervention in both cases. They already appeared as bilaterally MG, and patients
      underwent a total thyroidectomy, in one case after 1 year of treatment with
      levothyroxine (LT4). CONCLUSIONS: MG treatment remains controversial. There is an
      increasing trend to a more radical surgery decreasing recurrence risk. Treatment
      with LT4 may be tested but it is rarely effective. Regardless of the therapeutic
      option, these children should be followed up and they should know about the
      possibility of goiter regeneration and the need for reintervention.

PMID- 28749784
TI  - Concentrations of leptin, adiponectin and other metabolic parameters in non-obese
      children with Down syndrome.
AB  - BACKGROUND: Recent data indicates that adults with Down syndrome (DS) are at
      increased risk for cardiovascular disease (CVD) that significantly contributes to
      their morbidity and mortality. Although identification of cardiometabolic risk
      factors during childhood is desirable to design preventive interventions, the
      data on such risk factors in children with DS is scarce. The aim of this study
      was to study the cardiometabolic risk factors such as insulin resistance (IR),
      leptin and adiponectin concentrations, lipid abnormalities and leptin resistance
      in non-obese children with DS. METHODS: This cross-sectional case control study
      included karyotype confirmed trisomy-21 DS children aged 2-12 years and their
      matched healthy controls. After detailed anthropometry, weight, height and body
      mass index (BMI) standard deviation scores (SDSs) were calculated with reference
      data. Laboratory evaluation included determination of fasting lipid parameters,
      insulin, glucose, leptin and adiponectin concentrations. The homeostasis model
      assessment method (HOMA-IR) was used to assess IR and the ratio of leptin to BMI
      was used as an index of leptin resistance. RESULTS: Seventy-seven children (39
      with DS and 38 controls) comprised the study cohort. The anthropometric
      parameters were similar in the two groups. Children with DS showed significantly
      higher mean leptin concentrations (2.098+/-1.68 ng/mL vs. 1.44+/-0.52 ng/mL, p
      value: 0.00) and higher indices of leptin resistance (0.127+/-0.085 vs. 0.09+/
      0.03, p-value: 0.001) as compared to controls. Fasting adiponectin concentrations
      were lower (20.64+/-19.87 ng/mL vs. 32.58+/-34.25 ng/mL, p-value: 0.21) and
      fasting glucose higher (89.25+/-8.12 mg/dL vs. 85.71+/-5.52 mg/dL, p-value: 0.06)
      in the DS group as compared to the controls but the differences did not reach
      statistical significance. The concentrations of insulin, various lipid parameters
      and calculated HOMA-IR values were similar in the two groups. In the DS group,
      five children were identified to have high (>75th centile) leptin levels and four
      as impaired fasting glucose as compared to none in the controls. CONCLUSIONS:
      Alterations of several cardiometabolic risk factors, in particular, leptin
      concentrations and leptin resistance are present in children with DS. The
      presence of hyperleptinemia without hyperinsulinemia suggests a probable inherent
      genetic basis for increased leptin resistance in patients with DS. There is a
      need for larger studies to further understand increased leptin resistance in DS
      that may contribute to increased CVD related morbidity and mortality in these
      patients.

PMID- 28749785
TI  - Mutation analysis of the NKX2.5 gene in Iranian pediatric patients with
      congenital hypothyroidism.
AB  - BACKGROUND: The embryonic development of the thyroid gland is regulated by the
      expression of several candidate genes which are related to congenital
      hypothyroidism. These genes include the numerous critical thyroid transcription
      factors such as NKX2.1, NKX2.5, FOXE1, and PAX8. The molecular analysis of these
      loci will be essential to the explanation of the participation of these
      transcription activators in the etiology of hypothyroidism. Among them, the role
      of NKX2.5 is important during the early thyroid morphogenesis and in controlling
      thyroidal cell differentiation and migration. Importantly, NKX2.5 change
      nucleotides are recognized to be central to the genesis of congenital
      hypothyroidism. METHODS: A case-control study was conducted in 65 unrelated
      patients, diagnosed with primary congenital hypothyroidism and all of them were
      diagnosed according to the clinical presentations of thyroid hypoplasia and
      without cardiovascular defects. Mutational screening of the entire NKX2-5 coding
      sequence was performed in a cohort of pediatric patients by PCR-SSCP and direct
      sequencing. RESULTS: We identified two known variations 73C>T (R25C) and 63A>G
      (E21E) in patients with thyroid hypothyroidism. Both of them are located in
      conserved region of the gene and previously reported in cases with thyroid
      dysgenesis and congenital heart defects. There was a significance association
      between 63A>G variation with primary hypothyroidism (p=0.003). CONCLUSIONS: These
      SNPs are probably related to thyroid hypoplasia because the allele frequency of
      the 63A>G polymorphism was significantly different in patients and controls and
      also R25C variation not observed in healthy cases.

PMID- 28749786
TI  - High resolution SPM imaging of organic molecules with functionalized tips.
AB  - One of the most remarkable and exciting achievements in the field of scanning
      probe microscopy (SPM) in the last years is the unprecedented sub-molecular
      resolution of both atomic and electronic structures of single molecules deposited
      on solid state surfaces. Despite its youth, the technique has already brought
      many new possibilities to perform different kinds of measurements, which cannot
      be accomplished by other techniques. This opens new perspectives in advanced
      characterization of physical and chemical processes and properties of molecular
      structures on surfaces. Here, we discuss the history and recent progress of the
      high resolution imaging with a functionalized probe by means of atomic force
      microscopy (AFM), scanning tunnelling microscopy (STM) and inelastic electron
      tunneling spectroscopy (IETS). We describe the mechanisms responsible for the
      high-resolution AFM, STM and IETS-STM contrast. The complexity of this technique
      requires new theoretical approaches, where a relaxation of the functionalized
      probe is considered. We emphasise the similarities of the mechanism driving high
      resolution SPM with other imaging methods. We also summarise briefly significant
      achievements and progress in different branches. Finally we provide brief
      perspectives and remaining challenges of the further refinement of these high
      resolution methods.

PMID- 28749787
TI  - Highly efficient biosensors by using well-ordered ZnO/ZnS core/shell nanotube
      arrays.
AB  - We have studied the fabrication of highly efficient glucose sensors using well
      ordered heterogeneous ZnO/ZnS core/shell nanotube arrays (CSNAs). The modified
      electrodes exhibit a superior electrochemical response towards
      ferrocyanide/ferricyanide and in glucose sensing. Further, the fabricated glucose
      biosensor exhibited good performance over an acceptable linear range from 2.39 *
      10-5 to 2.66 * 10-4 mM, with a sensitivity of 188.34 mA mM-1 cm-2, which is
      higher than that of the ZnO nanotube array counterpart. A low limit of detection
      was realized (24 MUM), which is good compared with electrodes based on
      conventional structures. In addition, the enhanced direct electrochemistry of
      glucose oxidase indicates the fast electron transfer of ZnO/ZnS CSNA electrodes,
      with a heterogeneous electron transfer rate constant (K s) of 1.69 s-1. The fast
      electron transfer is attributed to the high conductivity of the modified
      electrodes. The presented ZnS shell can facilitate the construction of future
      sensors and enhance the ZnO surface in a biological environment.

PMID- 28749788
TI  - Two-terminal transport measurements with cold atoms.
AB  - In recent years, the ability of cold atom experiments to explore condensed-matter
      related questions has dramatically progressed. Transport experiments, in
      particular, have expanded to the point in which conductance and other transport
      coefficients can now be measured in a way that is directly analogous to solid
      state physics, extending cold-atom-based quantum simulations into the domain of
      quantum electronic devices. In this topical review, we describe the transport
      experiments performed with cold gases in the two-terminal configuration, with an
      emphasis on the specific features of cold atomic gases compared to solid-state
      physics. We present the experimental techniques and the main experimental
      findings, focusing on-but not restricted to-the recent experiments performed by
      our group. We finally discuss the perspectives opened up by this approach, the
      main technical and conceptual challenges for future developments, and potential
      applications in quantum simulation for transport phenomena and mesoscopic physics
      problems.

PMID- 28749789
TI  - Surgical approach to piles at risk of severe postoperative pain: tricks and tips.
AB  - AIM: Aim of the present study is to propose a clinic-therapeutic course for the
      treatment of hemorrhoidal disease able to combine radical anatomic surgery with a
      painless postoperative path. MATERIAL OF STUDY: The present study is based on the
      evaluation of 20 selected patients who underwent radical hemorrhoidectomy for
      very high grade hemorrhoidal disease. The clinical course was characterized by
      careful bowel cleansing, hemorrhoidectomy according to Milligan-Morgan using
      LigaSure, intraoperative perianal infiltration of Ropivacaine and postoperative
      use of analgesic drugs. DISCUSSION: A low postoperative pain may descend from a
      scheduled timing of clinical procedures. Preoperative bowel cleansing delays the
      first postoperative evacuation, thus avoiding the perianal nerve stimulation. The
      use of LigaSure allows to perform surgical excision in a perfect way: lack of
      hemostatic stitches, less tissue trauma, very low early morbidity. A rational and
      scheduled intra and postoperative drug administration offers a highly significant
      contribution to the pain control. The intra and postoperative use of drugs makes
      it possible to perform the so-called "preventive anesthesia with activation of
      the pain memory" and postoperative evacuations with low pain perception. All
      patients, in fact, reported low and well tolerated pain, satisfaction and return
      to normal activities in a short period. CONCLUSIONS: Radical hemorrhoidectomy
      with LigaSure and attention to pre, intra and postoperative protocol makes the
      procedure painless, safe and with low morbidity. KEY WORDS: Hemorrhoidectomy,
      LigaSure, Painless procedure.

PMID- 28749790
TI  - Do we need to screen for de-novo diabetes mellitus in chronic hepatitis C
      patients after a sustained virological response?
AB  - BACKGROUND AND AIM: There are millions of chronic hepatitis C (CHC) virus
      infected patients who have been treated with a combination therapy (interferon
      and ribavirin) and have achieved a virological response (SVR) worldwide. The aim
      of this study is to evaluate the risk factors for de-novo diabetes mellitus in
      CHC patients treated with combination therapy (interferon and ribavirin) and have
      achieved an SVR. PATIENTS AND METHODS: A total of 214 nondiabetic CHC patients
      with SVR and baseline homeostasis model assessment (HOMA) less than or equal to 2
      were divided into group A, which included 108 patients with a BMI less than 25,
      and group B, which included 106 patients with a BMI of at least 25 and less than
      30. HOMA insulin resistance (IR) and BMI were measured at the baseline, at
      achievement of an SVR, and 1 year after achievement of an SVR. Leptin levels were
      assessed at baseline and 1 year after achievement of an SVR in patients with
      increased BMI. RESULTS: One year after SVR, 36 (33.33%) patients from group A
      developed increasing BMI with no significant changes in HOMA versus that at SVR
      (P=0.53), but showed a significant reduction versus baseline HOMA (P=0.02). In
      group B, 68 (64.1%) patients showed increased BMI of at least 25, with a
      significant increase in HOMA versus that at SVR (P=0.02), and with no significant
      reduction versus baseline HOMA (P=0.44). In group B, serum leptin showed a
      significant reduction 12 months after achievement of an SVR versus baseline in
      patients with increased BMI. Six patients from group B with increased BMI after 1
      year developed de-novo IR and type two diabetes mellitus. CONCLUSION: In
      nondiabetic CHC patients with SVR and baseline BMI of at least 25, the post-SVR
      increase in BMI predisposed to an increase in HOMA-IR and could be considered a
      predisposing factor for diabetes mellitus.

PMID- 28749791
TI  - Enhanced Adherence in Patients Using an Automated Home Medication Dispenser.
AB  - BACKGROUND: Many factors contribute to medication nonadherence including
      psychological and memory disorders, aging, and pill burden. The Automated Home
      Medication Dispenser (AHMD) is a medication management system intended to help
      solve unintentional medication nonadherence. OBJECTIVE: The purpose of this study
      was to determine if use of the AHMD improved medication adherence. METHODS: We
      conducted a 6-month prospective, feasibility study assessing use of the AHMD in
      21 patient-caregiver dyads. Patients were referred by their physician because of
      poor medication adherence and included if they resided in Rochester, NY and on at
      least two medications in pill form. Pill counts were performed at baseline to
      assess previous adherence. Prospective medication adherence was assessed using
      AHMD recorded dosing information. A paired t-test was used to compare previous
      and prospective adherence. RESULTS: The mean age of patients was 75.1 years.
      Fifteen patients (71.4%) and eight caregivers (38.1%) were women; half (47.6%) of
      caregivers lived with the patient. The most common patient comorbidities were
      hypertension (76.2%) and memory disorder (61.9%). Mean adherence increased from
      49.0% at baseline to 96.8% after 6 months of AHMD use (p < .001). CONCLUSION: In
      a cohort of unintentionally nonadherent patients, use of the AHMD for 6 months
      significantly improved medication adherence.

PMID- 28749792
TI  - Effect of Socioeconomic Status on Surgery Waiting Times and Mortality After Hip
      Fractures in Italy.
AB  - BACKGROUND: Reducing inequities is a main goal of the Italian healthcare system.
      We evaluated socioeconomic differences in delayed surgery and postoperative
      mortality after a hip replacement after a fracture in Piedmont Region (Italy).
      METHODS: Cohort study including all people aged >=65 years hospitalized for a hip
      fracture in 2007-2010 (n = 21,432). Study outcomes were the following: (1)
      surgery waiting times >2 days; (2) 30-day, 90-day, and 1-year mortality from
      admission. Log-binomial models were used to evaluate the effect of socioeconomic
      status on waiting time, adjusting for age, sex, comorbidities, biennium, and
      Local Health Unit. Logistic models were fitted for mortality, adjusting also for
      the type of intervention (prosthesis/reduction) and waiting time. RESULTS:
      Seventy percent of surgeries were performed beyond 2 days from admission; 30-day
      mortality was 4.1%, 90-day was 10.8%, and 1-year was 21.9%. Lower socioeconomic
      levels were associated with higher risk of waiting >2 days (Adjusted Relative
      Risk: 1.14) and higher odds for 90-day (Adjusted Odds Ratio: 1.18) and 1-year
      (Adjusted OR: 1.27) mortality. CONCLUSIONS: We found socioeconomic inequities in
      access to hip replacement and postoperative outcomes. Strengthening the
      connection between hospital, primary care and rehabilitation services, improving
      regional monitoring systems and taking into account quality of care in funding
      health system, may contribute to guarantee uniform levels of healthcare quality
      in Italy.

PMID- 28749793
TI  - PAX8 Expression in Solitary Fibrous Tumor: A Potential Diagnostic Pitfall.
AB  - PAX8 is used as a diagnostic aid in classifying retroperitoneal (RP) spindle cell
      tumors. PAX8 positivity in a spindled RP tumor is typically associated with
      sarcomatoid renal cell carcinoma (SRCC). However, PAX8 expression in solitary
      fibrous tumor (SFT), a tumor not uncommon to the RP, has not been extensively
      studied. We investigated the expression of PAX8 in SFTs and other spindle cell RP
      tumors. We collected 30 SFT, 23 SRCC, 11 gastrointestinal stromal tumors, 2
      synovial sarcomas, 6 dedifferentiated liposarcomas (DDLS), 4 well differentiated
      liposarcomas (WDLS), and select other tumors. We identified nuclear PAX8
      expression in 13 of 30 (43%) SFT, 0 of 6 (0%) DDLS, and 1 of 4 (25%) WDLS. Twenty
      eight of 30 (93%) SFT, 0 of 23 (0%) SRCC, 2 of 6 (33%) DDLS, and 1 of 4 (25%)
      WDLS showed nuclear STAT6 expression. All gastrointestinal stromal tumors were
      negative for both PAX8 and STAT6. Of the 13 SFT showing PAX8 expression, 8 showed
      diffuse expression and 5 expressed PAX8 focally. Extrapleural SFTs were more
      likely to express PAX8 compared with pleural SFTs (10/13; 77% vs. 3/17; 18%,
      respectively; P=0.00117). Twenty of 23 (87%) SRCC expressed PAX8; the sarcomatoid
      component of all 23 SRCC was negative for STAT6. Of the other spindle cell tumors
      studied, 1 of 2 synovial sarcomas and 1 of 2 histiocytic sarcomas showed PAX8
      expression. Pathologists should be aware of the potential pitfall of the
      relatively frequent expression of PAX8 by SFT and STAT6 expression in
      liposarcoma. PAX8 expression by a spindle cell lesion of RP would not allow
      distinction between SFT, SRCC, or sclerosing liposarcoma by itself. A STAT6/PAX8
      phenotype excludes SRCC.

PMID- 28749794
TI  - United European Gastroenterology Week scientific abstracts and their progression
      to full publication.
AB  - OBJECTIVE: Abstracts presentations at scientific meetings enable rapid
      dissemination of novel research. The percentage of abstracts that proceed to full
      publication from differing medical specialties is highly variable. This study
      aims to evaluate the outcomes of abstracts presented at the United European
      Gastroenterology Week (UEGW). MATERIALS AND METHODS: All abstracts presented at
      UEGW between 2009 and 2011 were assessed. Cross-referencing of the first author,
      senior author and at least one keyword of the abstract was performed using PubMed
      and EMBASE databases. Abstracts and possible resultant full publications were
      then examined in tandem to ensure that they represented the same study. Data were
      also collected on lag time to publication, journal impact factors, country of the
      author and factors influencing subsequent publication. RESULTS: A total of 6785
      abstracts (1438 oral and 5347 poster presentations) were presented during the
      period assessed. Of these, 2099 (30.9%) proceeded to full publication in indexed
      journals. Oral abstract presentations were most likely to proceed to full
      publication compared with poster presentations (odds ratio: 1.38, 95% confidence
      interval: 1.22-1.56) and were more likely to achieve publication in higher impact
      journals (median impact factor 4.78 vs. 2.89, P<0.0005). The median lag time to
      full publication was 15 (IQR: 7-15) months. The Netherlands had the highest
      United European Gastroenterology abstract conversion rate to full publication
      (46.8%). CONCLUSION: This is the first study to assess the publication rates of
      UEGW. Findings are favourable with similar studies from other societies.

PMID- 28749795
TI  - Hepatotoxicity After Immune Checkpoint Inhibitor Therapy in Melanoma: Natural
      Progression and Management.
AB  - OBJECTIVE: To report the clinical features, treatment, and outcomes of patients
      with immune checkpoint inhibitor-induced hepatotoxicity. PATIENTS AND METHODS: In
      this retrospective observational study, we identified patients with metastatic
      malignant melanoma seen in consultation and/or treated between March 2011 and
      March 2016. Hepatotoxicity was assessed using the Common Terminology Criteria for
      Adverse Events, v4.0. RESULTS: Seventeen patients were identified as having any
      degree of hepatotoxicity by history (grade 1 to 4). Twelve of 17 were diagnosed
      after ipilimumab, 3 of 17 were diagnosed after pembrolizumab, and 2 of 17 after
      ipilimumab combined with nivolumab. Median time from first dose of immune therapy
      to hepatotoxicity was 52 days. Clinical symptoms were variable: asymptomatic,
      fatigue, myalgias, headache, abdominal pain, nausea, vomiting, confusion, and/or
      jaundice. Eight patients had concurrent adverse events including colitis,
      hypophysitis, pneumonitis, and/or rash. Immune therapy was discontinued in all
      patients except 3. The patients were most commonly treated with systemic
      corticosteroids such as prednisone. Immunosuppression was discontinued by taper
      over a median of 42 days; in 3 patients steroids had to be reinitiated based on
      clinical or laboratory worsening of liver tests. Normalization of liver tests was
      seen within a median of 31 days of immunosuppression initiation. One patient with
      grade 4 hepatotoxicity had normalization with the addition of cyclosporine.
      CONCLUSIONS: Melanoma patients treated with immune checkpoint inhibitors should
      be monitored regularly for hepatotoxicity. Treatment with discontinuation of
      therapy and initiation of corticosteroids is indicated with grade 3 or 4
      hepatotoxicity. Cyclosporine may be beneficial in steroid-refractory
      hepatotoxicity.

PMID- 28749797
TI  - The ethics/advocacy connection.

PMID- 28749796
TI  - Irrigation Device Successfully Tests Valve Competence During Minimally Invasive
      Mitral Valve Repair.
AB  - Minimally invasive mitral valve repair has become standard. We hypothesized that
      reproducible water testing with less air contaminations may help achieve
      successful repair and prevent air embolism. We used a long shaft irrigation
      device connected to an infuser pump to water test mitral valve repair in 104
      consecutive patients with severe mitral regurgitation due to type II mitral valve
      dysfunction. All patients underwent mitral valve repair via small right
      thoracotomy. Water testing was performed by simultaneously monitoring root
      pressure to confirm valve competence and adequate leaflet coaptation with
      suitable pressure. Irrigation was stopped when root pressure reached 60 mm Hg.
      Simultaneous transesophageal echocardiography showed a negligible amount of air
      introduction. Predischarge echocardiography revealed residual mitral
      regurgitation of less than or equal to 1 in all patients, and no patient
      experienced any major adverse event such as stroke or perioperative myocardial
      infarction. This novel water test allowed us to correctly check mitral valve
      competence and reduce air contamination.

PMID- 28749798
TI  - Inspirational leaders: The ideal mentors.

PMID- 28749800
TI  - Nurse communication's effect on CMS Star Ratings.

PMID- 28749801
TI  - Interprofessional collaboration through technology.

PMID- 28749802
TI  - Are your Gen X nurses satisfied?

PMID- 28749803
TI  - The Chi Cart ministry.

PMID- 28749804
TI  - Behavioral health: A natural nursing fit.

PMID- 28749805
TI  - Hazardous terrain and tranquil waters.
AB  - Leadership development insights for nurse managers.

PMID- 28749806
TI  - Safeguard your staff against violence.

PMID- 28749807
TI  - Post-Chernobyl Investigations of Radiocesium Activity Concentrations in Cistern
      Waters along the Croatian Coast of the Adriatic Sea.
AB  - The results of long-term investigations into the post-Chernobyl period of
      radiocesium activity concentrations in cistern waters along the Croatian coast of
      the Adriatic Sea are presented. The Cs activity concentrations in cistern water
      samples were in excellent correlation with fallout activities. The observed mean
      residence time of Cs in cistern waters was estimated to be 6.9 +/- 0.8 y. Cesium
      137 radioecological sensitivity for the period 1988-1997 for cistern water was
      estimated to be 1.17 * 10 Bq y L/(Bq m). The annual total effective dose incurred
      by Cs and Cs that a hypothetical adult person drinking 1 L of cistern water per
      day would receive was estimated to be < 1 mSv in 1986, decreasing to 3.6 MUSv in
      2015.

PMID- 28749808
TI  - Body Surface Contamination Levels of Residents under Different Evacuation
      Scenarios after the Fukushima Daiichi Nuclear Power Plant Accident.
AB  - Body surface contamination levels should be correlated with inhaled actual
      thyroid doses during evacuation following the Fukushima Daiichi nuclear power
      plant (FDNPP) accident. Evacuees and residents were screened for body surface
      contamination using a Geiger-Mueller survey meter. The authors obtained 7,539
      individual screening data sheets as well as gamma-spectrometry data from
      measurements made on clothing of two subjects by using a germanium spectrometer.
      Body surface contamination levels were analyzed in four residential groups during
      two different periods: 12-14 and 15-17 March 2011. Contamination levels during 12
      14 March in the Tomioka/Okuma/Futaba/Naraha group were very low, indicating that
      residents evacuated before the radioactive plume reached their towns on 12 March.
      In contrast, levels in the Namie and Minamisoma groups were higher than those in
      the other groups in both periods, indicating that these residents were exposed to
      plumes twice on 12 and 15-16 March. The plume on 12 March was enriched with short
      lived radionuclides: averaged proportions of radioactivity (relative to I) from
      Te, I, and Cs measured in clothing from two subjects were 2.3, 1.1, and 0.1,
      respectively, after correction for physical decay by 12:00 on 12 March. These
      proportions are similar to those (relative to I) from Te and Cs in dust sampled
      by a high-volume air sampler in the zone 20 km from the FDNPP on 12 March: 1.9
      and 0.1, respectively. These data indicate that the relative contribution to
      inhaled thyroid dose of short-lived radionuclides in radioactive plumes released
      on 12 March could be as much as 37.5% in 1-y-old children.

PMID- 28749809
TI  - Beyond Californium-A Neutron Generator Alternative for Dosimetry and Instrument
      Calibration in the U.S.
AB  - Evaluations of neutron survey instruments, area monitors, and personal dosimeters
      rely on reference neutron radiations, which have evolved from the heavy reliance
      on (alpha,n) sources to a shared reliance on (alpha,n) and the spontaneous
      fission neutrons of californium-252 (Cf). Capable of producing high dose
      equivalent rates from an almost point source geometry, the characteristics of Cf
      are generally more favorable when compared to the use of (alpha,n) and (gamma,n)
      sources or reactor-produced reference neutron radiations. Californium-252 is
      typically used in two standardized configurations: unmoderated, to yield a
      fission energy spectrum; or with the capsule placed within a heavy-water
      moderating sphere to produce a softened spectrum that is generally considered
      more appropriate for evaluating devices used in nuclear power plant work
      environments. The U.S. Department of Energy Cf Loan/Lease Program, a longtime
      origin of affordable Cf sources for research, testing and calibration, was
      terminated in 2009. Since then, high-activity sources have become increasingly
      cost-prohibitive for laboratories that formerly benefited from that program.
      Neutron generators, based on the D-T and D-D fusion reactions, have become
      economically competitive with Cf and are recognized internationally as important
      calibration and test standards. Researchers from the National Institute of
      Standards and Technology and the Pacific Northwest National Laboratory are
      jointly considering the practicality and technical challenges of implementing
      neutron generators as calibration standards in the U.S. This article reviews the
      characteristics of isotope-based neutron sources, possible isotope alternatives
      to Cf, and the rationale behind the increasing favor of electronically generated
      neutron options. The evaluation of a D-T system at PNNL has revealed
      characteristics that must be considered in adapting generators to the task of
      calibration and testing where accurate determination of a dosimetric quantity is
      necessary. Finally, concepts are presented for modifying the generated neutron
      spectra to achieve particular targeted spectra, simulating Cf or workplace
      environments.

PMID- 28749810
TI  - Selective Shielding of Bone Marrow: An Approach to Protecting Humans from
      External Gamma Radiation.
AB  - The current feasibility of protecting emergency responders through bone marrow
      selective shielding is highlighted in the recent OECD/NEA report on severe
      accident management. Until recently, there was no effective personal protection
      from externally penetrating gamma radiation. In Chernobyl, first-responders wore
      makeshift lead sheeting, whereas in Fukushima protective equipment from gamma
      radiation was not available. Older protective solutions that use thin layers of
      shielding over large body surfaces are ineffective for energetic gamma radiation.
      Acute exposures may result in Acute Radiation Syndrome where the survival
      limiting factor up to 10 Gy uniform, homogeneous exposure is irreversible bone
      marrow damage. Protracted, lower exposures may result in malignancies of which
      bone marrow is especially susceptible, being compounded by leukemia's short
      latency time. This highlights the importance of shielding bone marrow for
      preventing both deterministic and stochastic effects. Due to the extraordinary
      regenerative potential of hematopoietic stem cells, to effectively prevent the
      deterministic effects of bone marrow exposure, it is sufficient to protect only a
      small fraction of this tissue. This biological principle allows for a new class
      of equipment providing unprecedented attenuation of radiation to select marrow
      rich regions, deferring the hematopoietic sub-syndrome of Acute Radiation
      Syndrome to much higher doses. As approximately half of the body's active bone
      marrow resides within the pelvis region, shielding this area holds great promise
      for preventing the deterministic effects of bone marrow exposure and
      concomitantly reducing stochastic effects. The efficacy of a device that
      selectively shields this region and other radiosensitive organs in the abdominal
      area is shown here.

PMID- 28749811
TI  - Application of NCRP 156 Wound Models for the Analysis of Bioassay Data from
      Plutonium Wound Cases.
AB  - The NCRP 156 wound model was heavily based on data from animal experiments. The
      authors of the report acknowledged this limitation and encouraged validation of
      the models using data from human wound exposures. The objective of this paper was
      to apply the NCRP 156 wound models to the bioassay data from four plutonium
      contaminated wound cases reported in the literature. Because a wide variety of
      forms of plutonium can be expected at a nuclear facility, a combination of the
      wound models-rather than a single model-was used to successfully explain both the
      urinary excretion data and wound retention data in three cases. The data for the
      fourth case could not be explained by any combination of the default wound
      models. While this may possibly be attributed to the existence of a category of
      plutonium whose solubility and chemistry are different than those described by
      the NCRP 156 default categories, the differences may also be the result of
      differences in systemic biokinetics. The concept of using a combination of
      biokinetic models may be extended to inhalation exposures as well, where more
      than one form of radionuclide-particles of different solubility or different
      sizes-may exist in a workplace.

PMID- 28749812
TI  - Investigation of Natural Radioactivity in a Monazite Processing Plant in Japan.
AB  - Monazite is a naturally occurring radioactive material that is processed for use
      in a variety of domestic applications. At present, there is little information
      available on potential radiation doses experienced by people working with
      monazite. The ambient dose rate and activity concentration of natural
      radionuclides in raw materials, products, and dust in work sites as well as the
      Rn and Rn concentrations in work sites were measured in a monazite processing
      plant in Japan. Dose estimations for plant workers were also conducted. The
      activity concentration of the U series in raw materials and products for the
      monazite processing plant was found to be higher than the relevant values
      described in the International Atomic Energy Agency Safety Standards. The ambient
      dose rates in the raw material yard were higher than those in other work sites.
      Moreover, the activity concentrations of dust in the milling site were higher
      than those in other work sites. The Rn concentrations in all work sites were
      almost the same as those in regular indoor environments in Japan. The Rn
      concentrations in all work sites were much higher than those in regular indoor
      environments in Japan. The maximum value of the effective dose for workers was
      0.62 mSv y, which is lower than the reference level range (1-20 mSv y) for
      abnormally high levels of natural background radiation published in the
      International Commission of Radiological Protection Publication 103.

PMID- 28749813
TI  - Preliminary Determination of Activation Products for a Varian Truebeam Linear
      Accelerator.
AB  - Medical linear accelerators used to treat various forms of cancers are operated
      at a number of different energies. A by-product of the high-energy photons
      produced by accelerators is activation of components within the machine itself
      and its surrounding bunker. The activation products pose radiological and
      regulatory challenges during the operation of the accelerator as well as when it
      is time for final decommissioning. The Varian TrueBeam is a new state-of-the-art
      linear accelerator now operating in the Canadian market. There is currently
      limited information on the production of its activation products and the
      resulting impacts on operation and decommissioning. In this paper, activation
      products in the Varian TrueBeam accelerator are experimentally determined by
      performing gamma spectroscopy using a portable high purity germanium detector. A
      total of 10 isotopes are identified for the conditions tested, which include Na,
      Al, Mn, Ni, Cu, Cu, Br, Sb, Sb, W. The half-lives of these isotopes range from
      2.3 min to 60.2 d. These preliminary results indicate that a decommissioning case
      similar to other radiotherapy accelerators can be made.

PMID- 28749816
TI  - Associations of rs823128, rs1572931, and rs823156 polymorphisms with reduced
      Parkinson's disease risks.
AB  - The PARK16 locus is considered to play a protective role in Parkinson's disease
      (PD). However, the epidemiological evidence on the relationships between PARK16
      single-nucleotide polymorphisms (rs823128, rs1572931, and rs823156) and PD is
      inconsistent. Therefore, we carried out a meta-analysis to validate the
      relationships and performed a bioinformatic analysis to explore putative
      regulation mechanisms of the single-nucleotide polymorphisms in PD. Through meta
      analysis, we confirmed that minor variants of rs823128A>G, rs1572931C>T, and
      rs823156A>G played protective roles in PD. Through bioinformatic analysis, we
      predicted that rs823128, rs1572931, and rs823156 as noncoding variants of NUCKS1,
      RAB29, and SLC41A1, respectively, might affect PD risk by altering the
      transcription factor-binding capability of the genes. These findings suggest new
      clues for PD research and potential targets for PD prevention and treatment.

PMID- 28749817
TI  - Prednisolone and Prednisone Pharmacokinetics in Pediatric Renal Transplant
      Recipients-A Prospective Study.
AB  - BACKGROUND: Prednisolone is a standard component of immunosuppressive protocols
      in renal transplantation (Tx) and despite standardized treatment regimens,
      adverse side effects are still frequent. The aim of this study was to
      characterize the pharmacokinetics of prednisolone and prednisone in pediatric
      renal transplant recipients in the first 52 weeks post Tx, to describe the
      relationship between prednisolone and prednisone, and to investigate a possible
      relationship between the development of new-onset diabetes after Tx (NODAT) and
      glucocorticoid exposure. METHODS: Renal transplant recipients receiving
      prednisolone (n = 11, age 1-15 years) were included in this prospective open
      label, descriptive, nonrandomized, and noninterventional study. Blood samples
      were drawn pre-Tx and during selected dose intervals (0, 1, 2, 4, 6, and 12 hours
      postdose; less frequent in children <10 kg) at 1, 2, 3, 4, 12, and 52 weeks post
      Tx. Concentrations of prednisolone and cortisol, their inactive keto forms, plus
      methylprednisolone, were measured using a validated LC-MS/MS method. Genetic
      variants in the CYP3A4, CYP3A5, ABCB1, and HSD11B2 genes were analyzed using real
      time polymerase chain reaction and Sanger sequencing. Correlation with NODAT was
      investigated. RESULTS: The patients displayed considerable intra- and inter
      individual variability in prednisolone exposure, with up to 5-fold differences in
      the area under the concentration-time curve (AUC). There were up to 7-fold
      differences in prednisolone/prednisone AUC ratio between patients, and patients
      experiencing NODAT tended to have a higher ratio (>12) compared with patients
      without NODAT (<12). Genetic variants in CYP3A5 and ABCB1 were found, but due to
      the limited study population causality cannot be definitive. CONCLUSIONS: The
      study suggests that a high prednisolone/prednisone AUC ratio may be a possible
      risk factor for NODAT. Further studies of individualization of glucocorticoid
      treatment in pediatric organ Tx are warranted.

PMID- 28749818
TI  - Fatal Septic Shock Triggered by Donor Transmitted Varicella Zoster Virus
      Reinfection 3 Days After Lung Transplantation.

PMID- 28749819
TI  - Engraftment and Repopulation Potential of Late Gestation Fetal Rat Hepatocytes.
AB  - BACKGROUND: The limited availability of donor organs has led to a search for
      alternatives to liver transplantation to restore liver function and bridge
      patients to transplantation. We have shown that the proliferation of late
      gestation (embryonic day 19) fetal rat hepatocytes is mitogen-independent and
      that mechanisms regulating mRNA translation, cell cycle progression, and gene
      expression differ from those of adult rat hepatocytes. In the present study, we
      investigated whether E19 fetal hepatocytes can engraft and repopulate an injured
      adult liver. METHODS: Fetal hepatocytes were isolated using a monoclonal antibody
      against a hepatic surface protein, leucine amino peptidase (LAP). LAP+ and LAP-
      fractions were analyzed by immunofluorescence and microarray. Immunopurified E19
      liver cells from DPPIV+ rats were transplanted via splenic injection into partial
      hepatectomized DPPIV- rats that had been pretreated with mitomycin C. RESULTS:
      More than a third of LAP+ fetal hepatocytes expressed ductal markers.
      Transcriptomic analysis revealed that these dual-expressing cells represent a
      population of less well-differentiated hepatocytes. Upon transplantation, LAP+
      late gestation fetal hepatocytes formed hepatic, endothelial, and ductal colonies
      within 1 month. By 10 months, colonies derived from LAP+ cells increased so that
      up to 35% of the liver was repopulated by donor-derived cells. CONCLUSIONS: Late
      gestation fetal hepatocytes, despite being far along in the differentiation
      process, possess the capacity for extensive liver repopulation. This is likely
      related to the unexpected presence of a significant proportion of hepatocyte
      marker-positive cells maintaining a less well-differentiated phenotype.

PMID- 28749820
TI  - Mounting Clinical Evidence With Tacrolimus Generic Products.

PMID- 28749821
TI  - Missed Opportunities: Adapting the HIV Care Continuum to Reduce HIV-Related
      Deaths.
AB  - INTRODUCTION: With advances in HIV care, persons with HIV/AIDS (PWHA) can lead
      healthy lives, but avoidable HIV-related deaths continue to occur in New York
      City (NYC). METHODS: We selected PWHA from our surveillance registry who died
      between 2007 and 2013, resided in NYC, and survived >=15 months after diagnosis
      to generate an HIV Mortality Reduction Continuum of Care (HMRCC) describing
      predeath care patterns among PWHA. We used HIV laboratory test reports to measure
      care outcomes during an "intervenable period" during which deaths may have been
      avoided. The continuum was stratified by the underlying cause of death (HIV
      related vs. other), and the HIV-related HMRCC was stratified by demographic
      characteristics. RESULTS: Eleven thousand one hundred eighty-seven analysis
      eligible PWHA died during 2007-2013. Ninety-eight percent linked to care; 80%
      were retained in care during the intervenable period; 66% were prescribed
      antiretroviral therapy; 47% had viral load <=1500 copies/mL; and 40% achieved
      viral suppression (VS). Half (47%) of the deaths were HIV-related. Retention was
      higher among HIV-related cause of death (83% vs. 78%) but VS was lower (34% vs.
      46%). The HIV-related HMRCC revealed disparities in VS. Despite comparable
      retention rates, whites had the highest VS (42%, vs. 32% blacks and 33%
      Latinos/Hispanics). In addition, retention and VS increased with increasing age.
      People with a history of injection drug use had relatively high rates of
      retention (88%) and VS (37%). DISCUSSION: The HMRCC is a novel framework for
      evaluating predeath care patterns among PWHA and identifying opportunities to
      reduce preventable deaths. In NYC, reducing mortality will require increasing VS
      among those already in care, particularly for blacks and Latinos/Hispanics.

PMID- 28749822
TI  - Comparison of Hepatitis B Virus Infection in HIV-Infected and HIV-Uninfected
      Participants Enrolled in a Multinational Clinical Trial: HPTN 052.
AB  - OBJECTIVE: Data comparing hepatitis B virus (HBV) infection in HIV-infected
      [HIV(+)], and HIV-uninfected [HIV(-)] individuals recruited into the same study
      are limited. HBV infection status and chronic hepatitis B (cHB) were
      characterized in a multinational clinical trial: HIV Prevention Trials Network
      (HPTN 052). METHOD: HBV infection status at enrollment was compared between
      HIV(+) (N = 1241) and HIV(-) (N = 1232) from 7 HBV-endemic countries. Hepatitis B
      e antigen and plasma HBV DNA were determined in cHB. Median CD4, median plasma
      HIV RNA, and prevalence of transaminase elevation were compared in HIV(+) with
      and without cHB. Significance was assessed with chi, Fisher exact, and median
      tests. RESULTS: Among all participants, 33.6% had HBV exposure without cHB (8.9%
      isolated HBV core antibody, "HBcAb"; 24.7% HBcAb and anti-HB surface antibody
      positive, "recovered"), 4.3% had cHB, 8.9% were vaccinated, and 53.5% were
      uninfected. Data were similar among HIV(+) and HIV(-) except for isolated HBcAb,
      which was more prevalent in HIV(+) than HIV(-) [10.1% vs. 7.7%, P = 0.046].
      Median HBV DNA trended higher in HIV(+) than in HIV(-). In HIV(+) with cHB versus
      those without cHB, transaminase elevations were more prevalent (alanine
      aminotransferase <= grade 2, 12% vs. 5.2%, P = 0.037; aspartate aminotransferase
      <= grade 2, 26% vs. 6.0%, P < 0.001), CD4 trended lower, and HIV RNA was similar.
      CONCLUSIONS: HBV infection status did not differ by HIV infection status. HIV co
      infection was associated with isolated HBcAb and a trend of increased HBV DNA. In
      HIV, cHB was associated with mild transaminase elevations and a trend toward
      lower CD4.

PMID- 28749823
TI  - Rates of Primary and Secondary Syphilis Among White and Black Non-Hispanic Men
      Who Have Sex With Men, United States, 2014.
AB  - BACKGROUND: Men who have sex with men (MSM) in the United States experience an
      approximately 100-fold greater rate of primary and secondary (P&S) syphilis
      diagnoses compared with men who have sex with women only. As in the general
      population, racial/ethnic disparities in P&S syphilis diagnosis rates may exist
      among MSM, but MSM-specific P&S syphilis rates by race/ethnicity are unavailable.
      We enhanced a published modeling approach to estimate area-level MSM populations
      by race/ethnicity and provide the first estimates of P&S syphilis among black and
      white non-Hispanic MSM. METHODS: We used data from the American Community Survey
      (ACS), published findings from the National Health and Nutrition Examination
      Survey (NHANES), and national syphilis surveillance data to estimate state-level
      rates of P&S syphilis diagnoses among MSM, overall and for black and white non
      Hispanic MSM. We also used variability around ACS and NHANES estimates to
      calculate 95% confidence intervals for each rate. RESULTS: Among 11,359 cases of
      P&S syphilis among MSM with known race/ethnicity in 2014, 72.5% were among white
      (40.3%) or black (32.2%) MSM. The national rate of P&S syphilis diagnosis was
      168.4/100,000 for white MSM and 583.9/100,000 for black MSM. Regional rates for
      black MSM ranged from 602.0/100,000 (South) to 521.5/100,000 (Midwest) and were
      consistently higher than those for white MSM. CONCLUSIONS: Although white MSM
      accounted for more P&S syphilis diagnoses than black MSM in 2014, when evaluating
      diagnoses based on rate per 100,000, black MSM had consistently and markedly
      higher rates than white MSM, with the highest impacted states located in the US
      South.

PMID- 28749825
TI  - A Fortified Donor Milk Policy is Associated With Improved In-Hospital Head Growth
      and Weight Gain in Very Low-Birth-Weight Infants.
AB  - BACKGROUND: Previous research has reported that infants fed donor milk grow
      slower than those fed formula. However, most of the trials used unfortified donor
      milk, which limits the ability to generalize the results to current clinical
      practice. PURPOSE: To evaluate the impact of early human milk feeding (donor milk
      and/or mother's own milk) with standard fortification on in-hospital growth of
      very low-birth-weight infants. METHODS: This pre-/postretrospective study
      included selected newborn infants less than 1500 g admitted to a level IV
      neonatal intensive care unit before and after the introduction of a policy
      providing donor milk when mother's own milk was not available in sufficient
      quantity to meet her infant's need. When enteral feeds reached 80 mL/kg per day,
      all human milk was fortified. RESULTS: Seventy-two "before" (any formula-fed) and
      114 "after" (human milk-fed) infants were enrolled in this study. Infant
      characteristics and neonatal morbidity were similar in both groups. Outcomes
      revealed that an initial human milk diet with standard fortification was
      associated with significantly higher early extrauterine weight gain and head
      growth in very low-birth-weight infants than a formula-fed diet. IMPLICATIONS FOR
      PRACTICE: Very early initiation of fortified breast and/or donor milk feeding can
      help promote in-hospital head growth and weight gain of preterm infants. Formula
      may not be appropriate for early use among preterm infants. IMPLICATIONS FOR
      RESEARCH: Further large-scale clinical trials are needed to determine the best
      initiation and composition of enteral feeding for preterm infants.

PMID- 28749824
TI  - The Relationship Between Efavirenz as Initial Antiretroviral Therapy and Suicidal
      Thoughts Among HIV-Infected Adults in Routine Care.
AB  - BACKGROUND: Evidence about the effect of initiating efavirenz-containing
      combination antiretroviral therapy (ART) as the first-line therapy on suicidal
      thoughts remains conflicting. METHODS: Using data from a cohort of HIV-infected
      adults enrolled in routine care across 5 sites in the United States, we included
      participants with a baseline patient-reported outcome measure and detectable
      viral load who initiated ART between 2011 and 2014. Participants were followed
      until the earliest of the following: first suicidal thoughts, discontinuation of
      initial ART regimen, death, loss to care (>12 months with no HIV appointments),
      or administrative censoring (2014-2015). Suicidal thoughts were measured using a
      Patient Health Questionnaire-9 item. We used weighted marginal structural Cox
      models to estimate the effect of initiating efavirenz-containing ART, versus
      efavirenz-free ART, on the hazard of active or passive suicidal thoughts after
      ART initiation, accounting for confounding by channeling bias. RESULTS: Overall,
      597 participants were followed for a median of 19 months (13,132 total person
      months); 147 (25%) initiated efavirenz-containing ART. At ART initiation, 38% of
      participants reported suicidal thoughts or depressive symptoms. Initiating
      efavirenz-based ART was associated with a hazard ratio (HR) for suicidal thoughts
      below the null in the crude analysis [HR, 0.88; 95% confidence interval (CI):
      0.53 to 1.45] and above the null in the weighted analysis (HR, 1.21; 95% CI: 0.66
      to 2.28). Among those with a prior mental health issue, the weighted HR was 1.76
      (95% CI: 0.45 to 6.86). CONCLUSIONS: After accounting for measured channeling
      bias, we observed no strong evidence that initiating efavirenz-containing ART
      increased the hazard of suicidal thoughts.

PMID- 28749827
TI  - Incident Review.

PMID- 28749826
TI  - Fathers' Needs and Masculinity Dilemmas in a Neonatal Intensive Care Unit in
      Denmark.
AB  - BACKGROUND: Most healthcare professionals in neonatal intensive care units
      typically focus on the infants and mothers; fathers often feel powerless and find
      it difficult to establish a father-child relationship. In family-centered
      healthcare settings, exploring fathers' experiences and needs is important
      because men's roles in society, especially as fathers, are changing. PURPOSE: To
      describe fathers' needs when their infants are admitted to a neonatal intensive
      care unit and to discuss these needs within a theoretical framework of
      masculinity to advance understanding and generate meaningful knowledge for
      clinical practices. METHODS: This qualitative study used participant observation,
      interviews, multiple sequential interviews, and a focus group discussion. Data
      were analyzed using grounded theory principles. RESULTS: Analysis of the fathers'
      needs generated 2 primary themes: (1) Fathers as caregivers and breadwinners and
      (2) fathers and emotions. Fathers wished to be involved and to take care of their
      infants but have to balance cultural and social norms and expectations of being
      breadwinners with their wishes to be equal coparents. IMPLICATIONS FOR
      PRACTICE/RESEARCH: Health professionals in neonatal intensive care units must be
      aware of fathers' need and desire to be equal coparents. Nurses should play a key
      role by, for example, showing that fathers are as important to their infants as
      are the mothers, helping them become involved in childcare, and ensuring that
      they are directly informed about their children's progress. Further research in
      other cultural settings would contribute to knowledge regarding fatherhood and
      the role of fathers in childcare.

PMID- 28749828
TI  - Therapists' Metacognitive Monitoring of the Psychotherapeutic Process With
      Patients With Borderline Personality Disorder.
AB  - BACKGROUND: Therapy for borderline personality disorder (BPD) is challenging, in
      part, because of the impact of BPD on the therapeutic relationship. The
      therapist's metacognitive capacity within therapy may be perturbed due to the
      complexity of verbal and nonverbal affect and cognition in the therapeutic
      interchange; however, research on this issue is lacking. METHODS: Therapists
      (N=20 clinical psychologists) were asked to discuss the treatment process when
      working with their patients with BPD (N=40) and their patients with major
      depressive disorder (N=40). Verbatim transcripts of the therapists'
      verbalizations were then scored using computerized linguistic content analysis.
      RESULTS: When discussing their patients with BPD, clinicians used significantly
      fewer words associated with cognitive processes (think, understand, realize) or
      words indicating causation (cause, because, effect), and more first-person
      singular pronouns, and adverbs. When describing their depressed patients, the
      therapists used more words associated with negative emotions, anxiety, anger, and
      sadness than positive words. The results did not seem to be influenced by the
      therapists' age, sex, or years of experience. CONCLUSIONS: Reflection on the
      psychotherapeutic process with patients with BPD induced in therapists a self
      focused, emotionally intense linguistic style dominated by references to
      themselves and their experience of intense emotional states. These results
      suggest that, when describing their work with patients with BPD, therapists
      experience metacognitive challenges and mentalization processes that may parallel
      the challenges therapists face when thinking and working during the psychotherapy
      sessions themselves. The results underscore the important role of supervision in
      assisting therapists to organize their reflective processes when working with
      patients with BPD.

PMID- 28749829
TI  - The Presence of Childhood Attention Deficit/Hyperactivity Disorder May Be
      Associated With Interpersonal Sensitivity in Patients With Social Anxiety
      Disorder.
AB  - The goal of this study was to evaluate a possible association between childhood
      attention deficit/hyperactivity disorder (ADHD) and interpersonal sensitivity in
      patients with social anxiety disorder (SAD). The study involved 125 adult
      outpatients with a primary diagnosis of SAD. To evaluate childhood ADHD, the ADHD
      module of the Schedule for Affective Disorders and Schizophrenia for School Age
      Children-Present and Lifetime Version (K-SADS-PL) was used. Clinical and
      sociodemographic data were collected and clinical rating scales were completed.
      Mean total scores on the Interpersonal Sensitivity Measure were significantly
      higher in the group with SAD and ADHD than in the group with SAD without ADHD.
      Interpersonal Sensitivity Measure total scores were positively correlated with
      the severity of SAD symptoms and negatively correlated with mean age of onset of
      SAD. The presence of childhood ADHD may be associated with greater interpersonal
      sensitivity in patients with SAD.

PMID- 28749830
TI  - Characteristics of Patients Involved in Physical Assault in an Acute Inpatient
      Psychiatric Setting.
AB  - BACKGROUND: Although aggressive behavior in psychiatric settings is a major
      concern, very few studies have focused exclusively on physical assault in a
      general inpatient psychiatric population. OBJECTIVES: This study had 3 main
      goals: (1) to evaluate the prevalence of assaultive behavior in an acute
      psychiatric hospital; (2) to identify the clinical and socio-demographic factors
      associated with assaultive behavior during hospitalization; and (3) to explore
      whether a diagnosis of schizophrenia spectrum disorder increases the risk of
      assaultive behavior. METHODS: We conducted a retrospective chart review of
      patients admitted to acute units in a psychiatric hospital between 2009 and 2012.
      A subset of occurrence reports identified by a multidisciplinary team as
      "physical assault" was included in the analysis. Using logistic multivariate
      regression analysis, these patients were compared with a randomly selected
      nonassaultive control group, matched for length of stay to identify factors
      associated with assaultive behavior. RESULTS: Of 757 occurrence reports, 613 met
      criteria for significant assault committed by 356 patients over 309,552 patient
      days. The assault incident density was 1.98 per 1000 patient days. In the
      logistic regression model of best fit, the factors significantly associated with
      assaultive behavior were age, legal status, and substance use. A diagnosis of
      schizophrenia spectrum disorder was not significantly associated with assaultive
      behavior. CONCLUSIONS: Clinicians should take extra precautions for involuntarily
      admitted young patients with a history of substance use, as they are more likely
      to exhibit assaultive behavior. A diagnosis of schizophrenia spectrum disorder in
      itself is not significantly associated with assaultive behavior. Screening
      instruments such as the Dynamic Appraisal of Situational Aggression may be useful
      in assessing risk of assault.

PMID- 28749831
TI  - Targets for the Treatment of Insomnia in Veterans With Serious Mental Illness.
AB  - STUDY OBJECTIVES: Insomnia is pervasive among people with serious mental
      illnesses (SMI) and has a profound negative impact on their psychiatric symptom
      management and recovery. However, little is known about the factors that affect
      severity of insomnia in those with SMI. In addition, very few studies have
      explored whether evidence-based interventions developed for those without SMI are
      appropriate for or applicable to individuals with SMI. The purpose of this study
      was to test the role of arousal, dysfunctional cognitions about sleep, and sleep
      related behaviors in predicting severity of insomnia in a sample of 60 Veterans
      who were receiving care in Veterans Health Administration mental health and
      psychosocial rehabilitation programs and who reported subjective insomnia. In
      addition, information was collected regarding the types of insomnia treatments
      provided to these Veterans. METHODS: Participants completed assessments of
      insomnia severity and sleep-related arousal, behaviors, and cognitions. Medical
      records were reviewed to determine whether participants had been
      screened/assessed for insomnia and whether treatments for insomnia were provided
      before the date of referral to the study. Multiple regression was used to predict
      insomnia severity on the basis of these factors. RESULTS: Most participants
      (81.7%) reported moderate to severe insomnia, although only 3.3% had a diagnosis
      of insomnia in their medical records. Worry and helplessness about sleep were
      predictive of insomnia severity; better self-reported sleep hygiene and higher
      levels of arousal were also associated with greater severity of insomnia.
      Education about sleep hygiene and medication were the only types of insomnia
      treatment received. CONCLUSIONS: Similar to insomnia among individuals without
      SMI, insomnia in Veterans with SMI is associated with dysfunctional sleep-related
      behaviors and cognitions. Many of the Veterans also lacked access to settings and
      resources conducive to healthy sleep. Veterans with SMI should be regularly
      assessed for insomnia. Research is needed concerning optimal evidence-based
      insomnia interventions for addressing behaviors and cognitions in this population
      in the context of these challenges.

PMID- 28749832
TI  - Politics in the Consulting Room.
AB  - The recent presidential campaign and election have had a strong impact on many
      patients and clinicians. This guest column and its introduction by Dr Eric
      Plakun, who edits the psychotherapy section of the journal, note the
      inevitability that we will all self-disclose, while describing some of the pros
      and cons and impacts of self-disclosure of a clinician's political perspectives.

PMID- 28749833
TI  - Clinical Barriers to Effective Treatment of Eating Disorders and Co-occurring
      Psychiatric Disorders in Transgendered Individuals.
AB  - Eating disorders (EDs) are complex and difficult to treat illnesses that are
      often chronic and disabling on their own accord or due to comorbidity with other
      psychiatric conditions. Historically, EDs have been viewed as illnesses of
      heterosexual, affluent white females. This stereotype increases the likelihood
      that these disorders will be underrecognized in the lesbian, gay, bisexual, and
      transgender community, as well as in different gender, socioeconomic, and ethnic
      populations. Our case report illustrates the clinical difficulties of managing a
      patient who presented to inpatient treatment with complaints of depression and
      suicidality, but who also had an active ED and was transgender.

PMID- 28749834
TI  - Transgender Youth in the Inpatient Psychiatric Setting: A Literature Review and
      Case Report.
AB  - Once considered pathological, transgenderism is now accepted as a variant of
      normal sexuality. As society has become more accepting of transgenderism,
      increasing numbers of transgender patients have begun to seek psychiatric care,
      and younger populations are embracing their gender differences. There is a
      paucity of literature on how best to serve transgender youth in psychiatric
      inpatient units. In this article, we share our experience and discuss the need
      for practical guidelines to help the inpatient psychiatrist navigate key topics
      related to this population. We then present a case report to illustrate several
      of these issues. A major goal of this report is to increase the literature base.

PMID- 28749835
TI  - A Model for Incident Review Committees in Behavioral Health Settings.
AB  - Despite the fact that incident review committees have been a key component of
      quality improvement in behavioral health settings for decades, specific models of
      how these committees are structured and operate are not well described. We
      present a model for an incident review committee that has been implemented in 2
      large, academic acute care psychiatric hospitals. We believe the model not only
      permitted us to efficiently and effectively review untoward incidents, but that
      it also provided an approach to calibrating standards of care for the
      institution, engaging physicians in an interdisciplinary effort, promulgating a
      culture of quality review and improvement throughout the organization, promoting
      continuity and sustainability of the incident review process, and, most
      importantly, driving beneficial change in clinical practice. Demonstration of the
      effectiveness of this model requires formal investigation.

PMID- 28749836
TI  - Anatomic Study of Ophthalmic Artery Embolism Following Cosmetic Injection.
AB  - INTRODUCTION: Cosmetic injections of dermal fillers or fat could cause ophthalmic
      artery embolism and even blindness, the high-risk regions of which are considered
      glabellar, nasal dorsum, and nasolabial fold. Understanding anatomy of the
      related arteries is important for a physician to safely perform filler
      injections. To investigate the mechanisms of ophthalmic artery embolism following
      the injections, cadaver anatomy was studied. METHODS: Ophthalmic artery, facial
      artery, their branches, and anastomoses among them were anatomized in 12 fresh
      cadavers. Mimetic injections of hyaluronic acid were performed in glabellar
      region, nasal dorsum, and nasolabial fold, the relationships between injected
      filler and related arteries were then investigated. RESULTS: It was clearly found
      that 4 arteries were located in common injection regions and connected to
      ophthalmic artery: supratrochlear artery, supraorbital artery, dorsal nasal
      artery, and angular artery. In the glabellar region, the deep injection on the
      periosteum will be risky to injure supratrochlear artery and supraorbital artery,
      whereas in nasal dorsum and nasolabial fold, the sub- superficial musculo
      aponeurotic system layer injection has the possibility to injure dorsal nasal
      artery, angular artery, and facial artery. CONCLUSION: The anatomic mechanism of
      ophthalmic artery embolism is the anastomoses among the related arteries and
      ophthalmic artery. Based on the findings of the study, injections in periosteum
      layer at glabellar region or sub-superficial musculo aponeurotic system layer of
      nasal dorsum and nasolabial fold are not advised.

PMID- 28749837
TI  - Occlusion Guided Double-Barreled Fibular Osteoseptocutaneous Free Flap for
      Refined Mandibular Reconstruction Aided by Virtual Surgical Planning.
AB  - BACKGROUND: There were many articles about double-barreled fibular flap for
      mandibular reconstruction. The upper layer bone was suit for implant placement as
      a new alveolar. The lower layer was necessary for contour. But the accurate
      relationship between the 2 layers bone was rarely reported. OBJECTIVES: The
      purpose of this study was twofold: to evaluate the feasibility of the novel
      design of the double-barreled fibular flap from virtual surgery to actual result;
      to evaluate the accuracy and results of occlusion-guided double-barreled fibular
      free flap in mandible reconstruction. METHODS: From 2010 to 2016, 52 patients
      underwent segmental mandibular reconstruction with double-barreled fibular
      osteoseptocutaneous flaps with computer aided design/computer aided manufacturing
      technique. Preoperative computer tomographic (CT) scans were imported into Mimics
      10.01 software (Materialise, Leuven, Belgium) for surgical planning. The peroneal
      vessel pedicel was designed at the lower barrel segmental bone of the double
      barreled fibular flap. The double-barreled bone was strung with 16 mm fixation
      screws instead of mini-plate. Sixty-three dental implants placement was
      simultaneous in 30 patients and 32 dental implants placement was in second stage
      in 18 patients. Postoperative CT and digital imaging were evaluated to assess
      surgical accuracy using software. The pre- and postoperative morphometric
      measurements were compared using the Fisher exact t test. RESULTS: Two flaps
      occurred vascular crisis postoperatively. There was no flap necrosis. Four
      implants failed during 1 to 5 weeks postoperative. Sixty-six CT scans from 33
      patients who underwent partial mandibular resection were analyzed. The dimensions
      of the double-barreled fibula segments after osteotomy showed no difference from
      the preoperative virtual surgical planning (VSP). But the condylar locations
      showed a disposition out of the fossa (P < 0.05), between VSP and postoperative
      CT scans. There was no difference in implants between VSP and postoperative CT
      scans. CONCLUSIONS: The VSP of relationship of double-barreled fibular is
      important for segmental mandible reconstruction. The benefit of VSP was to
      enhance surgical accuracy and safety.

PMID- 28749838
TI  - Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation
      Necrosis.
AB  - BACKGROUND: Radiation necrosis is one of the complications of Gammaknife
      radiosurgery. The traditional treatment of radiation necrosis carries a high risk
      of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular
      endothelial growth factor, a known mediator of cerebral edema. It can be used to
      successfully treat brain radiation necrosis. PATIENT DESCRIPTION: Two patients
      with a history of small cell lung cancer presented with metastatic disease to the
      brain. They underwent Gammaknife radiosurgery to brain metastases. Several months
      later, magnetic resonance imaging showed radiation necrosis with significant
      surrounding edema. The patients had a poor response to treatment with
      dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2
      weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in
      significant clinical and radiographic improvement. CONCLUSION: Bevacizumab can be
      successfully used to treat radiation necrosis induced by Gammaknife radiosurgery
      in patients with cerebral metastases. It is of particular benefit in patients
      with poor reaction to corticosteroids and other medications.

PMID- 28749839
TI  - Angle-to-Angle Mandibular Defect Reconstruction With Fibula Flap by Using a
      Mandibular Fixation Device and Surgical Navigation.
AB  - PURPOSE: Although free fibula flaps are widely used for mandibular
      reconstruction, 3-dimensional (3D) position is difficult to control in angle-to
      angle mandibular defects. The present study describes a revised approach for
      angle-to-angle mandibular reconstruction with fibula flaps by using mandibular
      fixation device and surgical navigation. METHODS: Preoperative maxillofacial and
      fibular computed tomography (CT) scans were acquired, and CT data were imported
      into ProPlan CMF software. Virtual mandibulectomy was performed, and 3D fibula
      image was superimposed on the mandibular defect. The fibula flap was shaped
      according to virtual parameters and the stereo model. Surgical navigation was
      used to check and correct shaped segments. Position of the osteotomy lines and
      relevant parameters regarding the shape of the fibula flap were provided to the
      surgeon. A mandibular fixation device (Cibei, China) was fixed to bilateral
      mandibular ramus before mandibulectomy, which maintained normal mandibular width.
      Under computer navigation guidance, the fibula flap was accurately positioned in
      3D direction, and the defect could be precisely reconstructed despite the lack of
      stable occlusal relationship after osteotomy. RESULTS: Postoperative CT and 3D
      error analysis revealed that osteotomy lines and reconstruction contour matched
      well with preoperative planning. Using our method, we precisely recovered the
      original configuration of the mandible. Bilateral condyles were located in the
      temporomandibular joint fossae, and normal mandibular width was maintained.
      Compared with preoperative positions, the average shift on the remaining mandible
      was 0.803 +/- 0.502 mm (largest, 1.886 mm). Average shift in the reconstructed
      mandible was 0.281 +/- 0.300 mm, largest being 2.441 mm. CONCLUSIONS: We describe
      a novel method for angle-to-angle mandibular reconstruction with free fibula
      flap. A mandibular fixation device combined with computer-assisted techniques
      involving surgical navigation improved clinical outcomes of this procedure.

PMID- 28749840
TI  - Computed Tomography Research: Relative Anatomy of Caldwell-Luc Approach in
      Pterygopalatine Fossa Surgery.
AB  - With the development of endoscopic technique, Caldwell-Luc approach has more wide
      applications and becomes a common method of pterygopalatine fossa (PPF) surgery.
      Few data can be used in this approach to avoid injuring the vessels and nerves
      within this area. In this study, the authors used computed tomography to get the
      coordinates of inferior orbital fissure, foramen rotundum, sphenopalatine
      foramen, internal opening of pterygoid canal, the strangulation of PPF, and the
      greater palatine foramen with canine fossa as the origin. Parameters of 60
      patients (120 observations) between 35 and 55 years who have no experience of
      trauma or surgery before were involved in this study. The data were analyzed by
      SPSS, statistical software with the comparison between sexes and sides. After
      calculating the relative distances and angles between these points and canine
      fossa, the authors get the proportions of the upper part of PPF, and the
      pterygopalatine canal to PPF, respectively. The authors finally got the safety
      surgical range. The results are meaningful to safety in surgery and complication
      avoidance, which can be great references in clinical applications.

PMID- 28749841
TI  - The Effect of Microvascular Decompression on Hemifacial Spasm With
      Atherosclerosis of Vertebral Artery.
AB  - BACKGROUND: Microvascular decompression (MVD) is the most useful treatment for
      hemifacial spasm (HFS). In patients of vertebral artery (VA) compression of the
      facial nerve, MVD is often difficult. Many of the VA are obviously
      atherosclerotic. In this study, the authors retrospectively compared the effect
      of MVD for HFS associated with the atherosclerosis of vertebral artery (aVA) with
      that of MVD for HFS with normal vertebral artery (nVA). METHODS: A retrospective
      study of HFS treated by MVD was conducted between January 2014 and October 2015.
      There were 186 patients with VA-associated HFS who underwent their first MVD at
      the authors' institution. Among them, 52 patients of HFS were associated with aVA
      and 134 patients were associated with nVA. RESULTS: At 1 day, 7 days, 1 month, 3
      months, and 1 year after MVD surgery, in aVA group, the effective rate of MVD was
      80.77%, 80.77%, 82.00%, 79.59%, and 82.61%, the incidence rate of complication
      was 15.83%, 13.46%, 14.00%, 12.24%, and 10.87%; in nVA group, the effective rate
      of operation was 94.03%, 94.78%, 95.42%, 94.53%, and 95.12% (P < 0.05), the
      incidence rate of complication was 4.48%, 4.48%, 3.82%, 3.13%, and 1.63% (P <
      0.05). CONCLUSION: When the HFS was associated with the aVA, the effective rate
      of MVD was lower and the incidence of complication was higher than those
      associated with nVA. In MVD of HFS associated with aVA, the full decompression of
      the facial nerve and the minimal traction of surrounding tissue in the operation
      are the key to the success of MVD.

PMID- 28749842
TI  - Reconstruction of Large Postburn Facial-Scalp Scars by Expanded Pedicled
      Deltopectoral Flap and Random Scalp Flap: Technique Improvements to Enlarge the
      Reconstructive Territory.
AB  - The scars of face and scalp caused by burning often show as 1 large facial-scalp
      scar. The deltopectoral flap was recognized as one of the first choices for the
      facial scar reconstruction. However, this flap cannot cross the level of
      zygomatic arch traditionally when it was transferred with pedicle. When the flap
      reconstructed the facial-scalp scars with expanded random scalp flap, another
      flap was often needed to reconstruct the remaining temple and forehead scars. The
      authors reviewed 24 patients of large facial-scalp scars reconstructed by
      expanded pedicled deltopectoral flap and scalp flap with several technique
      improvements. The seaming scar between the deltopectoral flap and scalp flap in
      the temple region formed the new hairline. The technique improvements included
      ligation of the perforating branches of the transverse cervical artery and
      thoracoacromial artery when dissecting the pocket, the partial bolster
      compressive dressing to the distal part of the flap and dividing the pedicle
      partly as a delaying procedure before dividing the pedicle completely. Good skin
      compliance, normal contours, and emotional expression were noted. There were
      complications including expander exposure in 3 patients, stretch marks in 5
      patients, flap tip necrosis in 2 patients, and mild postoperative hypertrophic
      scars in 3 patients. In conclusion, the expanded pedicled deltopectoral flap can
      enlarge the reconstructive territory in face successfully with the technique
      improvements. The combination of the expanded pedicled deltopectoral flap and
      scalp flap is a reliable and excellent reconstructive option for large postburn
      facial-scalp scars.

PMID- 28749843
TI  - Three-Dimensional Imaging Anatomic Study and Clinical Application of the Third
      Ventricle Transcallosal-Transforniceal Approach.
AB  - The third ventricle is a narrow, funnel-shaped, unilocular, midline cavity
      located between the 2 thalami, under the body of the lateral ventricle, in the
      center of the head. Damaging of brain tissue in the third ventricle when
      conducting operation under the microscope will lead to serious consequence. The
      study aimed to precisely detect the relative location of specific structures on
      the approach to the third ventricle. The authors rebuilt a 3-dimensional
      reconstruction of the brain and selected specific sections and then measured
      several crucial distance, angle to precisely assure the approaching pathway and
      localize the hypothalamic sulcus, interthalamic adhesion, anterior commissure,
      optic chiasm, and pineal body. In the study, canthomeatal line was used as base
      line to measure angle. Parameters were obtained from 58 samples (22 males and 36
      females) between 21 and 76 years old. Means and standard deviation were
      calculated as well as the 95% confidence interval for the mean value of the
      measured data. The data were analyzed by SPSS, statistical software with the
      comparison between sexes and sides. The results could be reference for clinical
      and anatomic utilities.

PMID- 28749844
TI  - Effect of Preserving the Pituitary Stalk During Resection of Craniopharyngioma in
      Children on the Diabetes Insipidus and Relapse Rates and Long-Term Outcomes.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of
      preserving an infiltrated pituitary stalk during the resection of
      craniopharyngioma of pituitary stalk origin on postoperative outcomes and thus
      provide a theoretical basis for microsurgical treatment and prognosis. METHODS:
      We screened the clinical data of all 103 pediatric patients with
      craniopharyngioma undergoing surgical treatment at our department between January
      2006 and January 2013 and conducted a retrospective analysis of 82 patients with
      craniopharyngioma originating in the pituitary stalk. The patients were followed
      up from 12 months to 8 years. We analyzed the effect of preserving the pituitary
      stalk on the early and persistent diabetes insipidus rates, postoperative relapse
      rate, and mortality. RESULTS: In the total resection group (n = 67), the early
      and persistent diabetes insipidus rates were significantly lower in the 46
      patients (68.7%) with a pituitary stalk than in those whose pituitary stalk was
      removed (P < 0.05); no significant difference was observed in the relapse rate
      between the 2 subgroups (P > 0.05). In the subtotal resection group (n = 15), a
      significant difference was observed in the early and persistent diabetes
      insipidus rates (P < 0.05), but no significant difference was observed in the
      relapse rate between the patients with a pituitary stalk and those whose
      pituitary stalk was removed (P > 0.05). CONCLUSIONS: For children with
      craniopharyngioma of pituitary stalk origin, preserving the pituitary stalk has a
      significant effect on the early and persistent diabetes insipidus rates. When
      intraoperative exploration showed excessive adhesion between the tumor and
      pituitary stalk, we opted to preserve the pituitary stalk, which significantly
      reduced the early and persistent postoperative diabetes insipidus rates, without
      significantly increasing the relapse or mortality rate.

PMID- 28749845
TI  - Postnatal Development of the Spheno-occipital Synchondrosis: A Histological
      Analysis.
AB  - The spheno-occipital synchondrosis (SOS) in cranial base is an important growth
      center for the craniofacial skeleton, and also is a guide rail for development of
      the maxilla, midface, and mandible. Previous studies showed that SOS may be a
      treatment target for youngsters with midfacial hypoplasia and small cranial vault
      secondary to craniosynostosis. However, most of studies about the SOS are based
      on imaging data. In this study, we try to explore the characteristics of
      postnatal development of the mouse SOS based on histological analysis. Our
      findings showed that the width of the SOS in mice were gradually decreased from
      newborn mice to adult mice, and the SOS cartilage was gradually became small,
      then almost completely ossificated in adult mice. The resting and proliferative
      layers in SOS cartilage were gradually decreased, and almost only hypertrophic
      chondrocytes while no resting and proliferative layer chondrocytes in adult mice.
      The proliferative ability of SOS chondrocytes also gradually decreased. These
      findings will be of benefit for the further clinical treatment for patients with
      midfacial hypoplasia or small cranial vault secondary to craniosynostosis.
      Further evidence-based research about the clinical implication is necessary in
      future.

PMID- 28749846
TI  - Three-Dimensional Radiologic Study on Index Measurement of Endonasal Endoscopic
      Optic Nerve Decompression.
AB  - OBJECTIVE: To provide the radiologic basis for the clinical application of
      endonasal endoscopic optic nerve decompression (EEOND). METHODS: CTA images were
      used to observe the optic canal (OC) and related structures of 60 patients (120
      sides) with normal nasal, paranasal sinuses, OC, and other related structures.
      RESULTS: Optic canal could be classified as: the canal (10 sides, 8.33%), the
      semicanal (25 sides, 20.83%), the impression (49 sides, 40.83%), and the
      nonimpression (36 sides, 30%). According to its relationships with the sinuses,
      OC could be further typed as: ethmoid sinus (22 sides, 18.3%), sphenoid sinus (38
      sides, 31.7%), ethmoid and sphenoid sinus (60 sides, 50%). The thickness of OC
      medial wall is about 1.11 +/- 0.24 mm at orbital mouth, 0.87 +/- 0.25 mm at
      middle part and 1.19 +/- 0.27 mm at cranial mouth. The arc length of OC bone wall
      which can be opened from the sinus cavity is about 7.18 +/- 0.76 mm at orbital
      mouth, 8.27 +/- 0.93 mm at middle part, and 6.98 +/- 0.89 mm at cranial mouth.
      The length of the OC medial wall is 12.18 +/- 1.35 mm. In the three-dimensional
      Cartesian coordinate system that origined with the last point of middle turbinate
      root and oriented by temporal side, front side, and superior side, the
      coordinates of midpoints of OC medial wall are: (3.64 +/- 1.11, 8.48 +/- 1.65,
      23.14 +/- 2.67) at orbital mouth, (0.16 +/- 1.21, 3.99 +/- 1.80, 24.85 +/- 2.67)
      at middle part, and (-3.59 +/- 1.22, 0.77 +/- 2.13, 26.39 +/- 2.68) at cranial
      mouth. One length unit on the axes is a millimeter. CONCLUSION: Computed
      tomography (CT) scanning technique can measure the data of the OC in EEOND. It
      has great guiding significance for clinical operation.

PMID- 28749847
TI  - Optic Canal Decompression With Unexpected Changes in Cerebrospinal Fluid of the
      Optic Canal.
AB  - Optic neuritis is a common inflammatory disease of the optic nerve. And the
      cerebral spinal fluid (CSF) in the subarachnoid space of optic nerve is thought
      to be homogeneous as in spine. We report a case of optic neuritis, some
      unexpected opaque fluid observed to flow out from the optic canal during the
      optic canal decompression surgery when the CSF in spine is normal. One day after
      the surgery, the visual acuity of the patient improved dramatically to 0.4 from
      0.05. This report highlights the possible restrictive pathological changes of the
      CSF in the optic nerve of acute optic neuritis, which may be the reason of the
      dysfunction of the optic nerve.

PMID- 28749848
TI  - A Rare Eyeball Luxation After Cranioplasty and a Four-Year Follow-Up.
AB  - A rare patient of reducible eyeball luxation after cranioplasty in a child
      Crouzon syndrome was reported. To remedy the patient's chronic intracranial
      hypertension and brachycephaly, orbitofrontal advancement and cranial vault
      remodeling were carried out. About 25 days of postoperation, an acute eyeball
      luxation was observed, with the presence of a subcutaneous accumulation of liquid
      in the bilateral temporal regions. The dislocated eyeballs were brought back by
      applying gentle manual pressure. The patient received a conservative treatment
      without a tarsorrhaphy. The dislocation recurrence never occurred again. In a 4
      year follow-up, it was shown that the child's vision was normal and proptosis was
      improved by series craniofacial reconstructions.

PMID- 28749849
TI  - Treatment of Children With Congenital Severe Blepharoptosis by Frontalis
      Aponeurosis Flap Advancement Under General Anesthesia in a Single Incision.
AB  - PURPOSE: This study aimed to investigate the effect of frontalis aponeurosis flap
      advancement in children with congenital severe blepharoptosis. METHODS: A total
      of 23 cases (25 eyes) of children who had congenital severe blepharoptosis and
      poor levator function (<=4 mm) and received frontalis aponeurosis flap
      advancement treatment in the Plastic Surgery Department of the Children's
      Hospital of Fudan University from January 1, 2013, to January 1, 2015, were
      retrospectively analyzed to evaluate the postoperative effects. RESULTS: All
      patients (age range, 6-27 months) were followed up for an average duration of
      15.3 months. Twenty eyes (80%) had excellent effects, 2 eyes (8%) had good
      effects, and 3 eyes (12%) had poor effects. The average preoperative marginal
      reflex distance was 0.2 mm (-2 to 2 mm), and the postoperative average marginal
      reflex distance was 3.1 mm (1-4 mm). None of the patients showed hematoma,
      infection, keratohelcosis, symblepharon separation, ectropion, trichiasis, or
      other postoperative complications. CONCLUSION: Frontalis aponeurosis flap
      advancement could be used to treat congenital severe blepharoptosis with good
      short-term effects.

PMID- 28749850
TI  - Midline Suboccipital Endoscopic Transcerebellomedullary Fissure Keyhole Approach.
AB  - OBJECTIVE: To study the endoscopic anatomy of the 4th ventricle and lateral
      brainstem regions via the midline suboccipital endoscopic transcerebellomedullary
      fissure keyhole approach assisted by a neuronavigation system and discuss the
      feasibility and indications of this approach. MATERIALS AND METHODS: Craniotomy
      procedures performed via the midline suboccipital endoscopic
      transcerebellomedullary fissure keyhole approach were simulated on 8 adult
      cadaveric heads fixed by formalin, and the related anatomic structures in the 4th
      ventricles or around the brainstem were observed through the 0 degrees  endoscope
      or alternatively 30 degrees  one. A neuronavigation system was used to measure
      the exposed area of the floor of 4th ventricle, the maximum exposure range, the
      length of the floor of 4th ventricle, the shortest distance from the midpoint of
      posterior arch of atlas to the opening of the aqueduct in the 4th ventricle and
      to the jugular foramen on both sides, respectively. RESULTS: All the anatomic
      structures within the 4th ventricle and partial anatomic landmarks around
      brainstem were identified by means of the midline suboccipital endoscopic
      transcerebellomedullary fissure keyhole approach. The exposed area of the floor
      of 4th ventricle is 459.68 +/- 73.71 mm. However, the total exposed area is
      1601.70 +/- 200.76 mm. The length of the floor of 4th ventricle is 36.08 +/- 2.63
      mm. The shortest distance from the midpoint of posterior arch of atlas to the
      opening of the aqueduct in the 4th ventricle is 63.87 +/- 2.97 mm, to the jugular
      foramen on both sides, respectively, is 40.11 +/- 2.47 mm/40.30 +/- 2.31 mm.
      CONCLUSIONS: Midline suboccipital endoscopic transcerebellomedullary fissure
      keyhole approach can basically meet the medial and lateral route of the
      transcerebellomedullary fissure approach. A tumor within the 4th ventricle or
      near the jugular tubercle extending into the 4th ventricle through the
      cerebellomedullary fissure can be removed by this approach.

PMID- 28749851
TI  - Immunoglobulin G4 (IgG4)-Positive Ocular Adnexal Mucosa-Associated Lymphoid
      Tissue Lymphoma and Idiopathic Orbital Inflammation.
AB  - PURPOSE: To report clinical and pathological characteristics of idiopathic
      orbital inflammation and ocular adnexal mucosa-associated lymphoid tissue (MALT)
      lymphoma with immunoglobulin G4 (IgG4)-positive plasma cells. METHODS: A
      retrospective histopathological review and clinical case series. A total of 51
      biopsy samples from January 2005 to December 2015 were used in this study,
      including 21 cases of biopsy-confirmed idiopathic orbital inflammation and 30
      cases of biopsy-confirmed ocular adnexal MALT lymphoma. Most cases of ocular
      adnexal lymphoma were conjunctival tissue. Retrospective immunohistochemical
      studies were performed to estimate the IgG4 and IgG4/IgG ratios. Histopathologic
      features, demographic and clinical data, radiologic findings, treatment, and
      follow-up information for each patient were analyzed. RESULTS: Among idiopathic
      orbital inflammation, 6 (28.6%) of the 21 patients were diagnosed as "probable"
      ocular adnexal IgG4-related diseases and 13 (43.3%) of the 30 patients were
      diagnosed as MALT lymphoma with IgG4-positive plasma cells. Six cases of 13 IgG4
      positive MALT lymphoma group had contralateral chronic inflammatory lesions
      infiltrated by IgG4-positive plasma cells, which was significantly (p = 0.007)
      higher than that in the IgG4-negative group. Conjunctival involvement was 69% of
      the IgG4-positive MALT lymphoma cases. Bilateral involvement of the ocular adnexa
      was significantly (p = 0.02) more frequent among IgG4-positive MALT lymphoma
      patients than that in IgG4-positive idiopathic orbital inflammation patients.
      Recurrence rate in the IgG4-positive group was higher (p = 0.05) than that in the
      IgG4-negative group but not significantly. CONCLUSIONS: This study presented an
      unusual framework of ocular adnexal IgG4-related inflammation, in conjunctiva. It
      is important to understand contralateral chronic inflammatory lesions and their
      relationship with IgG4-positive MALT lymphoma. Tissue biopsy and IgG4
      immunostaining are required for all cases because IgG4-positive MALT lymphoma can
      arise from a pre-existing IgG4-positive chronic inflammatory lesions. This is the
      first study that performs IgG4 immunostaining for tissue from a relatively large
      number of conjunctival MALT lymphomas in a single center. Therefore, it will help
      to diagnose conjunctival lymphoproliferative disease.

PMID- 28749852
TI  - Complications Following Enucleations and Subsequent Oculoplastic Surgeries.
AB  - PURPOSE: To analyze the complications and subsequent type and frequency of
      oculoplastic surgeries after enucleation in adult patients. METHODS: The authors
      conducted a retrospective case note review of adult patients who underwent
      enucleation followed by placement of an alloplastic implant wrapped in donor
      sclera between 2001 and 2013. The data collected included patient demographics,
      surgical indication, implant size, postoperative complications, and subsequent
      oculoplastic surgical procedures. RESULTS: The authors included 186 patients who
      underwent enucleation during the study period. Malignancy was the leading cause
      for this operation (79.6%) followed by a blind painful eye (12.4%). Most
      postoperative complications were managed conservatively with an adjustment of the
      size of the ocular prosthesis. In most cases, the 20-mm and 22-mm implants were
      used, and implant size ranged from 16 to 22 mm. There was no correlation between
      implant size and complication rate. Twenty-six patients required subsequent
      surgery after enucleation (14%). In total, 9.7% (18 patients of 186) patients
      underwent eyelid surgery after enucleation, most frequently for blepharoptosis
      (7%). The interval between enucleation and eyelid surgeries was, on average, 1.9
      years. Less frequently, surgery is needed for socket repair for anterior surface
      breakdown (1.6%), and the interval between enucleation and socket surgery was 0.9
      years. CONCLUSIONS: The most frequent complications following enucleation were
      blepharoptosis and enophthalmos with a deep upper eyelid sulcus. About 15% of
      patients required subsequent oculoplastic procedures after, on average, 2 years,
      while surgery in the early postoperative phase was rarely indicated.

PMID- 28749853
TI  - The ICU Is Becoming a Main Battlefield for Severe Maternal Rescue in China: An 8
      Year Single-Center Clinical Experience.
AB  - OBJECTIVES: To review the characteristics of and to identify the reasons for
      severe maternal admissions to the ICU. DESIGN: This was an analytical,
      observational, open, and retrospective study. SETTING: In our ICU. PATIENTS: A
      total of 487 severe maternal cases were reviewed during the 8-year study period
      of January 2009 to December 2016. INTERVENTION: None. MEASUREMENTS AND MAIN
      RESULTS: A total of 487 severe maternal cases (12.6%) among the 3,867 patients
      admitted to ICU were reviewed. Of these, 361 patients were admitted for obstetric
      reasons, mainly pregnancy-induced hypertension (58.7%) and postpartum hemorrhage
      (36.8%). The remaining 126 patients were admitted for nonobstetric reasons,
      including cardiac-related disease (31.0%), immune-related disease (24.6%), and
      sepsis (20.6%). A total of 249 patients experienced combined comorbidities: the
      most common was a scarred uterus (100 patients; 40.2%), followed by endocrine
      related disease (25.3%), immune-related disease (21.3%), and cardiac-related
      disease (18.1%). Central venous insertion (90.6%) was the most common
      intervention, followed by arterial catheter insertion (33.7%), mechanical
      ventilation (11.7%), blood purification (5.7%), and invasive hemodynamic
      monitoring (3.7%). Nine patients died during the study period, of which the death
      of four could have been avoided. CONCLUSIONS: The number of severe maternal cases
      has increased annually in our ICU. Although obstetric causes remained the most
      common reason for admission, the nonobstetric causes and basic complications were
      too complex, dangerous, and beyond the reach of the obstetrician with regard to
      monitoring and treatment. We call for a multidisciplinary team mainly composed of
      ICU staff to improve severe maternal outcomes.

PMID- 28749854
TI  - Risk Stratification in Pediatric Acute Respiratory Distress Syndrome: A
      Multicenter Observational Study.
AB  - OBJECTIVES: The Pediatric Acute Lung Injury Consensus Conference developed a
      pediatric specific definition for acute respiratory distress syndrome (PARDS). In
      this definition, severity of lung disease is stratified into mild, moderate, and
      severe groups. We aim to describe the epidemiology of patients with PARDS across
      Asia and evaluate whether the Pediatric Acute Lung Injury Consensus Conference
      risk stratification accurately predicts outcome in PARDS. DESIGN: A multicenter,
      retrospective, descriptive cohort study. SETTING: Ten multidisciplinary PICUs in
      Asia. PATIENTS: All mechanically ventilated children meeting the Pediatric Acute
      Lung Injury Consensus Conference criteria for PARDS between 2009 and 2015.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on epidemiology,
      ventilation, adjunct therapies, and clinical outcomes were collected. Patients
      were followed for 100 days post diagnosis of PARDS. A total of 373 patients were
      included. There were 89 (23.9%), 149 (39.9%), and 135 (36.2%) patients with mild,
      moderate, and severe PARDS, respectively. The most common risk factor for PARDS
      was pneumonia/lower respiratory tract infection (309 [82.8%]). Higher category of
      severity of PARDS was associated with lower ventilator-free days (22 [17-25], 16
      [0-23], 6 [0-19]; p < 0.001 for mild, moderate, and severe, respectively) and
      PICU free days (19 [11-24], 15 [0-22], 5 [0-20]; p < 0.001 for mild, moderate,
      and severe, respectively). Overall PICU mortality for PARDS was 113 of 373
      (30.3%), and 100-day mortality was 126 of 317 (39.7%). After adjusting for site,
      presence of comorbidities and severity of illness in the multivariate Cox
      proportional hazard regression model, patients with moderate (hazard ratio, 1.88
      [95% CI, 1.03-3.45]; p = 0.039) and severe PARDS (hazard ratio, 3.18 [95% CI,
      1.68, 6.02]; p < 0.001) had higher risk of mortality compared with those with
      mild PARDS. CONCLUSIONS: Mortality from PARDS is high in Asia. The Pediatric
      Acute Lung Injury Consensus Conference definition of PARDS is a useful tool for
      risk stratification.

PMID- 28749855
TI  - Outcomes of Patient- and Family-Centered Care Interventions in the ICU: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To determine whether patient- and family-centered care interventions
      in the ICU improve outcomes. DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO,
      CINAHL, and the Cochrane Library databases from inception until December 1, 2016.
      STUDY SELECTION: We included articles involving patient- and family-centered care
      interventions and quantitative, patient- and family-important outcomes in adult
      ICUs. DATA EXTRACTION: We extracted the author, year of publication, study
      design, population, setting, primary domain investigated, intervention, and
      outcomes. DATA SYNTHESIS: There were 46 studies (35 observational pre/post, 11
      randomized) included in the analysis. Seventy-eight percent of studies (n = 36)
      reported one or more positive outcome measures, whereas 22% of studies (n = 10)
      reported no significant changes in outcome measures. Random-effects meta-analysis
      of the highest quality randomized studies showed no significant difference in
      mortality (n = 5 studies; odds ratio = 1.07; 95% CI, 0.95-1.21; p = 0.27; I =
      0%), but there was a mean decrease in ICU length of stay by 1.21 days (n = 3
      studies; 95% CI, -2.25 to -0.16; p = 0.02; I = 26%). Improvements in ICU costs,
      family satisfaction, patient experience, medical goal achievement, and patient
      and family mental health outcomes were also observed with intervention; however,
      reported outcomes were heterogeneous precluding formal meta-analysis.
      CONCLUSIONS: Patient- and family-centered care-focused interventions resulted in
      decreased ICU length of stay but not mortality. A wide range of interventions
      were also associated with improvements in many patient- and family-important
      outcomes. Additional high-quality interventional studies are needed to further
      evaluate the effectiveness of patient- and family-centered care in the intensive
      care setting.

PMID- 28749856
TI  - Evaluation of Prognostic Factors and Proposed Changes to the Modified Tokuhashi
      Score in Patients With Spinal Metastases From Breast Cancer.
AB  - STUDY DESIGN: A retrospective study of all patients with histologically confirmed
      breast cancer spinal metastases presenting to a single institution between May
      2001 and April 2012. OBJECTIVES: The aim of this study was to investigate whether
      the 2014mT is more accurate than the 2005mT. SUMMARY OF BACKGROUND DATA: The
      commonly used 2005 modified Tokuhashi score (2005mT) has become more inaccurate
      as oncologists move toward treating tumors according to their molecular and
      genomic profile, rather than their tissue-of-origin. In attempts to improve the
      accuracy of the 2005mT, a revised score (2014mT) was published, suggesting that
      hormone receptor negative and triple-negative breast cancer patients be given a
      modified Tokuhashi histological score of 3 rather than 5. METHODS: Demographic
      characteristics, tumor receptor status, clinical findings in relation to the
      primary tumor and its metastases, and actual survival time were collated. The
      2005mT was compared with the 2014mT. Univariate and multivariate Cox regression
      analyses were used to evaluate the influence of each parameter on survival, and
      receiver operating characteristic curves were used to determine predictive values
      of each score version. RESULTS: Of the 185 patients included, 32 underwent
      operative treatment, while 153 were managed nonoperatively for their spinal
      metastases. The overall cohort had a median survival time of 24 months following
      the diagnosis of spinal metastases, with a 6-month survival rate of 90%. Hormone,
      HER2 and triple-negative receptor statuses were significant predictors of poorer
      survival upon multivariate analysis (P = 0.004, P = 0.007, P < 0.001, and P <
      0.001, respectively). Age, the original Tokuhashi score components, previous
      breast surgery for cancer, previous radiotherapy to the breast, previous
      radiotherapy to the spine, previous chemotherapy, and previous immunotherapy were
      not significant. At 6 months, the 2005mT AUROC was 0.62, while that of the 2014mT
      was 0.64 (P = 0.5394). CONCLUSION: Tumor histological subtype is crucial when
      prognosticating the survival of patients with breast cancer spinal metastases.
      Although the 2014mT was marginally more accurate than the 2005mT, its predictive
      ability remains poor. LEVEL OF EVIDENCE: 3.

PMID- 28749857
TI  - Vertebral Endplate Defect as Initiating Factor in Intervertebral Disc
      Degeneration: Strong Association Between Endplate Defect and Disc Degeneration in
      the General Population.
AB  - STUDY DESIGN: Cross-sectional study of spine magnetic resonance in a population,
      predominantly female, sample. OBJECTIVE: To determine the relationship between
      vertebral endplate defect and intervertebral disc degeneration (DD) in general
      population. SUMMARY OF BACKGROUND DATA: Precise understanding of the mechanisms
      leading to DD development is lacking. In a degenerating disc, mechanical and
      structural changes lead to further worsening of disc integrity. Increasing
      attention has been paid to vertebral endplate defects as having a possible role
      in the etiopathogenesis of DD. METHODS: The study population comprised 831 twin
      volunteers from TwinsUK (mean age 54 +/- 8 yr, 95.8% female). Lumbar T2-weighted
      magnetic resonance images were coded for endplate defects from 8310 endplates
      into six grades. Total endplate score (TEP score) was achieved by summing both
      endplate defect grades from the same disc level. DD was evaluated using two
      different classifications; Pfirrmann grading, and a quantitative trait for DD
      based on a 4-point grading system. Multivariable regression analysis was used to
      determine relationships between the traits of interest and the known risk factors
      for DD, age, and body mass index (BMI). A receiver operator curve for TEP score
      predicting DD was generated, and survival analysis paired with Cox proportional
      hazards models analysis performed. RESULTS: There was statistically significant
      association between DD and age and BMI. These associations lost significance when
      TEP score was included as predictor in multivariable model. TEP score was
      strongly and independently associated at every lumbar disc level with DD
      (Pfirmann P<=0.001; 4-point grading systems P < 1e-16). A cut-off point score of
      5 for TEP score was found above which there was a higher DD prevalence. Across
      all age subgroups, probabilities of having DD were significantly increased in
      those considered TEP score positive (>=5). CONCLUSION: Our large, population
      based study has shown that endplate defect was strongly and independently
      associated with DD at every lumbar disc level. These results provide a mechanism
      by which increasing age and BMI predispose to DD. LEVEL OF EVIDENCE: 2.

PMID- 28749859
TI  - A Plea to Faculty: Rethink Student Writing Assignments.
AB  - Requiring students to submit poor papers doesn't serve anyone well.

PMID- 28749860
TI  - Anal Pap Tests to Decrease Anal Cancer Burden in HIV-Infected Patients.
AB  - Usually HPV related, the cancer is increasingly common in this population.

PMID- 28749863
TI  - Protecting Care for the Vulnerable.

PMID- 28749864
TI  - Nurses Try a Plant-Based Diet.

PMID- 28749865
TI  - Nurses Try a Plant-Based Diet.

PMID- 28749866
TI  - Nurses Try a Plant-Based Diet.

PMID- 28749867
TI  - Nurses Try a Plant-Based Diet.

PMID- 28749868
TI  - Low-Income Adults Report Better Health, Other Benefits, with the ACA.
AB  - Repeal efforts threaten to undo these gains-and have nursing implications, too.

PMID- 28749869
TI  - U.S. Life Expectancy Varies Depending on County of Birth.
AB  - These geographic disparities have been increasing over the past 35 years.

PMID- 28749872
TI  - Study Highlights the Need for Continuing Postapproval Drug Monitoring.
AB  - Follow-up on agents approved from 2001 to 2010 uncovered new safety concerns.

PMID- 28749874
TI  - New CDC Guideline for the Prevention of Surgical Site Infection.
AB  - This updates the 1999 original, published before formal evidence-based guidelines
      were in routine use.

PMID- 28749876
TI  - LGBT Older Adults in Long-Term Care.
AB  - Lesbian, gay, bisexual, and transgender elders continue to face health care
      disparities.

PMID- 28749877
TI  - Sucrose as Analgesia in Neonates Undergoing Painful Procedures.
AB  - Editor's note: This is a summary of a nursing care-related systematic review from
      the Cochrane Library. For more information, see http://nursingcare.cochrane.org.

PMID- 28749878
TI  - New Approvals in Cancer Treatment.

PMID- 28749879
TI  - Two Antiviral Drugs Approved For Adolescents With HCV.

PMID- 28749880
TI  - Codeine and Tramadol Contraindicated for Pediatric Use.

PMID- 28749884
TI  - Original Research: The Effects of Red Yeast Rice Supplementation on Cholesterol
      Levels in Adults.
AB  - : : Purpose: Red yeast rice (RYR) supplementation has become a popular
      alternative to statin therapy in treating hypercholesterolemia. This state-of-the
      science review seeks to explore the most recent evidence on the effectiveness and
      safety of RYR supplementation in treating dyslipidemic adults. METHODS: This
      review extends the time frame of a meta-analysis performed by Li and colleagues
      in 2014; specifically, we looked at the literature published between September
      2013 and April 2016. We conducted a search of four electronic databases-PsycINFO,
      CINAHL, PubMed, and Scopus-using the terms red yeast rice and cholesterol. We
      excluded studies that included berberine or lovastatin. RESULTS: Fifteen articles
      met the inclusion criteria. Eleven articles reported on randomized controlled
      trials, one reported on an open-label pilot study, and one reported on an open
      label clinical trial. Two articles were meta-analyses. The 13 studies involved a
      total of 1,246 participants, with an additional 7,467 participants reported in
      the two meta-analyses. Significant reductions in low-density lipoprotein
      cholesterol and total cholesterol levels with RYR supplementation were observed
      in all trials. There were no significant changes in liver and kidney function,
      and 10 studies noted no significant changes in creatine kinase levels.
      CONCLUSIONS: Although RYR appears to be a safe and effective lipid-lowering
      agent, there is insufficient evidence to support the recommendation of RYR
      supplementation to patients. Further research is needed, including long-term
      studies, studies that include participants with comorbidities and complex medical
      histories, and studies that take into account the variability of formulation and
      dosage of RYR in the marketplace.

PMID- 28749885
TI  - Good Nursing Is Good Antibiotic Stewardship.
AB  - : Resistance to antibiotics has increased dramatically in the United States, with
      serious associated medical, social, and economic consequences. The most promising
      approach to this national crisis is a new understanding of the need for the
      careful and responsible use of antibiotics, both for the benefit of society and
      for the optimal care of each patient. This multidisciplinary approach, called
      antimicrobial stewardship, has typically involved specialists but not necessarily
      nurses, who perform numerous antibiotic-related activities daily and should be an
      integral part of antimicrobial stewardship programs. In this article, we use
      patient examples to review several stewardship activities and illustrate how
      nurses are essential to the appropriate use of antibiotics.

PMID- 28749886
TI  - Daily Consumption of Fruit Juice is Associated with Slight Weight Gain in Young
      Children.

PMID- 28749887
TI  - Significant Rise in Nursery Product-Related Injuries After Years of Decline.

PMID- 28749888
TI  - Antibiotics are a Treatment Alternative for Acute Appendicitis in Children.

PMID- 28749889
TI  - Study Confirms Obesity Increases Risk of Death.

PMID- 28749890
TI  - Preventing Enteric Infections from Contact with Animals.
AB  - Precautions when visiting petting zoos and state fairs.

PMID- 28749891
TI  - The Power of Conversation.
AB  - Danielle Ofri's new book makes the case for listening closely to what patients
      say.

PMID- 28749892
TI  - International Nursing Congress Brings Together Nurses from Across the Globe.
AB  - AJN's editor-in-chief Shawn Kennedy and editorial board member and contributing
      editor Amanda Anderson attended the 2017 International Council of Nurses Congress
      May 27 to June 1 in Barcelona, and present the highlights here. This report
      expands on the summary posted on AJN's blog, Off the Charts: https://wp.me/p7sy0l
      6sD.

PMID- 28749893
TI  - Intimate Strangers.
AB  - A PICU nurse writes of walking with parents in their pain.

PMID- 28749894
TI  - Comparison of Outcomes Between Combined Transepithelial Photorefractive
      Keratectomy With and Without Accelerated Corneal Collagen Cross-Linking: A 1-Year
      Study.
AB  - PURPOSE: To investigate the effects of combined transepithelial photorefractive
      keratectomy (tPRK) and accelerated corneal collagen cross-linking (CXL) on visual
      acuity and refractive outcomes. METHODS: The medical records of 89 eyes (89
      patients) undergoing combined tPRK and CXL (tPRK-CXL group) or tPRK alone (tPRK
      group) were retrospectively analyzed. Uncorrected distance visual acuity (UDVA),
      corrected distance visual acuity, and manifest refraction spherical equivalent
      (MRSE) were evaluated preoperatively and 2 weeks, 1, 3, 6, and 12 months after
      surgery. RESULTS: At 2 weeks after surgery, the tPRK-CXL group had better UDVA
      than the tPRK group (0.97 +/- 0.22 vs. 0.85 +/- 0.22, P = 0.015). At 2 weeks and
      1 month after surgery, the tPRK-CXL group had a significantly lower spherical
      error than the tPRK group (0.24 vs. 0.63 D, P = 0.017, for 2 weeks and 0.43 vs.
      0.57 D, P = 0.019, for 1 month). At 12 months after surgery, the tPRK-CXL group
      had a lower spherical error and MRSE than the tPRK group (0.30 vs. 0.44 D, P <
      0.001, for the spherical error and 0.17 vs. 0.31 D, P < 0.001, for the MRSE).
      Both groups had comparable predictability, efficacy, and safety indices at 12
      months after surgery. CONCLUSIONS: Combined tPRK and accelerated CXL demonstrated
      comparable predictability, efficacy, and safety compared with tPRK alone.
      Combined tPRK and CXL provides better UDVA in the early postoperative period and
      better refractive outcomes at 12 months postoperatively in terms of spherical
      error and MRSE.

PMID- 28749895
TI  - Mechanical Modeling of a Keratoconic Cornea.
AB  - PURPOSE: We created a laboratory model of a cornea that was subjected to various
      pressures and thermal and mechanical factors to better understand the genesis of
      keratoconus deformation. METHODS: A steel base allowed for fixation of circular
      multilaminated patches of araldite (10 cm in diameter, 5 mm thick) in which the
      corneal anatomy was modeled. The model was plunged into a steam room (374 degrees
      F/3 bars of pressure for 1 h) to ensure thermal homogeneity and was subjected to
      pressure using compressed air. Three models were assessed: a fault-free model
      with no lesion (model 1), and 2 models with a defect. The first of the defective
      models (model 2) had an external crack-type lesion (1 cm long; 1 mm deep). The
      second defective model (model 3) had one quarter thinned down using abrasive
      sandpaper (thickness reduced by 30%-40%). RESULTS: For model 1, which represented
      a healthy cornea, homogeneous modification was noted when examined under
      polarized light. In model 2, no excessive deformation was noticed, but there were
      stress lines at the edge of the lesion. Model 3 had a deformity, similar to
      keratoconic deformation. CONCLUSIONS: Our findings suggest that the disease
      progresses under environmental stresses, but only when there is an initial
      defect, and especially when there is a thinning down defect. This thinning down
      defect may be induced by continual eye rubbing.

PMID- 28749896
TI  - Elimination of Anterior Corneal Steepening With Descemet Membrane Endothelial
      Keratoplasty in a Patient With Fuchs Dystrophy and Keratoconus: Implications for
      IOL Calculation.
AB  - PURPOSE: To report a case of coexistent Fuchs endothelial corneal dystrophy
      (FECD) and keratoconus (KCN) in which there was normalization of corneal
      topography after Descemet membrane endothelial keratoplasty (DMEK). METHODS:
      Retrospective medical record review. RESULTS: Preoperative findings revealed a
      best-corrected visual acuity of 20/40 with -1.00 - 2.50 * 147, topographic
      maximum keratometry of 50.8 D with inferior steeping, and confluent guttae in the
      left eye. Medical record review revealed myopic shift, but little change in
      keratometry or corneal thickness over the previous 3 years. The patient developed
      epithelial edema with contact lens trial, highlighting endothelial dysfunction
      and eliminating the option of contact lenses for visual rehabilitation. Combined
      DMEK and cataract extraction with intraocular lens implantation was undertaken.
      Postoperatively, best-corrected visual acuity was 20/20 with only spherical
      correction. Elimination of stromal edema led to flattening of maximum anterior
      keratometry to 46.3 D and reduction of total corneal refractive power (TCRP) by
      4.4 D. There was an unanticipated postoperative refractive error of +3.75 D
      consistent with this normalization of corneal topography. CONCLUSIONS: This is
      the first case report of the role of DMEK in normalizing corneal topography in
      coexistent FECD and KCN. The potential impact of DMEK on anterior curvature and
      TCRP must be considered in intraocular lens power calculation for cataract
      surgery in patients with FECD and KCN.

PMID- 28749897
TI  - Role of Scleral Contact Lenses in Management of Coexisting Keratoconus and
      Stevens-Johnson Syndrome.
AB  - PURPOSE: To report the rare coexistence of keratoconus and Stevens-Johnson
      syndrome (SJS) managed with scleral contact lenses (ScCLs). METHODS: This is a
      retrospective case series. Five patients (9 eyes) who had coexisting SJS and
      corneal ectasia were identified from the database during the 2-year period.
      Diagnosis of SJS was based on a positive history of drug reactions, signs of
      ocular surface disease, and the presence of keratinization of lid margins.
      Keratoconus was diagnosed by slit-lamp biomicroscopy. RESULTS: Five eyes of 3
      patients had coexisting SJS and keratoconus and were dispensed with ScCLs (PROSE,
      prosthetic replacement of the ocular surface ecosystem; Boston Foundation for
      Sight, Needham Heights, MA). All these patients had photophobia. Visual acuity
      improved in all these patients with ScCL wear. Two patients (4 eyes) were
      excluded from this study because they had SJS with generalized corneal thinning
      from limbus to limbus, corneal opacification, and pannus. One patient developed
      deep vessels in the cornea on prolonged ScCL wear. Reduction in the ScCL wear
      schedule and change of material with a higher Dk resulted in regression of
      vascularization. Case 3 developed conjunctival congestion and was uncomfortable
      wearing ScCLs, although visual acuity was 20/40. He discontinued using ScCL wear.
      CONCLUSIONS: Keratoconus, a noninflammatory condition of the cornea coexisted
      with inflammatory SJS. Managing such patients with ScCLs may improve vision and
      comfort.

PMID- 28749898
TI  - Recurrence of Granular Corneal Dystrophy Type 1 After Phototherapeutic
      Keratectomy, Lamellar Keratoplasty, and Penetrating Keratoplasty in a Single
      Population.
AB  - PURPOSE: To describe the recurrence of granular corneal dystrophy type 1 (GCD1)
      after penetrating keratoplasty (PKP), anterior lamellar keratoplasty (ALK), deep
      anterior lamellar keratoplasty (DALK), and phototherapeutic keratectomy (PTK) in
      a single population. The time required to achieve best-corrected visual acuity
      (BCVA) after each intervention was also analyzed. METHODS: Retrospective review
      of all patients with GCD1 from a single center between 1989 and 2016. Surgical
      interventions were performed 50 times on 28 eyes of 15 patients. Data were
      primarily analyzed through Cox regression modeling with clustering and robust log
      rank testing. RESULTS: Significant recurrence occurred most rapidly after PTK
      (median time 2.7 years) and was most delayed after PKP (13.7 years). Significant
      recurrence occurred at a similar interval after ALK and DALK (3.7 and 3.2 years,
      respectively). Significant recurrence-free survival was longer for PKP than for
      ALK, DALK, or PTK (P = 0.04). The time required to obtain BCVA was shorter in the
      PTK group (median 1.8 months) than in the PKP and DALK groups (median 5.3 and 8.4
      months, respectively; P = 0.03 and P = 0.02). All groups achieved a similar
      median BCVA (20/25-20/30). CONCLUSIONS: This series indicates that GCD1
      recurrence-free survival is longest after PKP with an associated delay in
      attaining BCVA. Conversely, PTK provided the fastest visual recovery with shorter
      recurrence-free survival.

PMID- 28749899
TI  - Effect of Donor and Recipient Diabetes Status on Descemet Membrane Endothelial
      Keratoplasty Adherence and Survival.
AB  - PURPOSE: To evaluate whether donor and/or recipient diabetes status affects the
      outcomes of Descemet membrane endothelial keratoplasty (DMEK). METHODS: A
      consecutive, single-center DMEK case series was reviewed. The outcome measures
      were success of surgeon tissue preparation, air reinjection rate, Kaplan-Meier 4
      year graft replacement/failure rate for any reason, and endothelial cell loss.
      RESULTS: The donor had a history of diabetes in 504 of 1791 cases (28%) and the
      recipient in 14%. For donors without and with diabetes, the preparation success
      rate was 99% versus 95% (P < 0.0001), the air reinjection rate was 16% versus 18%
      (P = 0.19), and the 4-year graft replacement/failure rate was 7% versus 9%,
      respectively (P = 0.15). Endothelial cell loss was not associated with donor
      diabetes (P = 0.76). For recipients without and with diabetes, the 4-year graft
      replacement/failure rate was 7% versus 9% (P = 0.68), and median endothelial cell
      loss increased from 27% versus 29% at 1 month to 42% versus 48% at 4 years,
      respectively (P = 0.02). Recipient use of insulin therapy was associated with
      poorer graft attachment and a higher air reinjection rate (P = 0.0023).
      CONCLUSIONS: Although donor diabetes was associated with a 5-fold increased risk
      of tissue preparation failure, it was not significantly associated with air
      reinjection, graft survival, or endothelial cell loss. This provides reassurance
      that tissue prepared successfully from donors with diabetes is safe to use for
      DMEK. Recipient diabetes was associated with increased endothelial cell loss; the
      potential effect on longer-term graft survival merits further study.

PMID- 28749900
TI  - Increase of Autonomic Nerve Factors in Epicardial Ganglionated Plexi During Rapid
      Atrial Pacing Induced Acute Atrial Fibrillation.
AB  - BACKGROUND The cardiac autonomic nervous system plays an essential role in
      epicardial ganglionated plexi (GP) regulation of atrial fibrillation onset and
      progression. To date, the activity of GP and the function of the cardiac
      autonomic nervous system are not well understood. The aim of this study was to
      determine alterations in epicardial GP cholinergic nerve, adrenergic nerve, and
      nerve growth factor expression using rapid atrial pacing to induce atrial
      fibrillation in canines. MATERIAL AND METHODS Nine healthy adult beagles were
      divided into two groups: the pacing experimental group (n=6) and the sham
      operation control group (n=3). For the pacing group, high frequency pacing of the
      left atrial appendage was performed for eight hours. In the control group,
      electrodes were implanted without rapid atrial pacing. Immunocytochemistry was
      used to identify neurons positively expressing tyrosine hydroxylase, choline
      acetyl transferase, nerve growth factor and neurturin. RESULTS After successfully
      establishing a rapid atrial pacing of the left atrial appendage induced atrial
      fibrillation model, we found that expression of choline acetyl transferase,
      tyrosine hydroxylase, nerve growth factor, and neurturin was significantly higher
      in the rapid atrial pacing group than the control group (p<0.05). CONCLUSIONS In
      our model, incremental excitability of both the adrenergic and cholinergic nerves
      led to frequent incidents of atrial fibrillation, which were possibly due to an
      imbalance of autonomic nerve factors in the epicardial GP during acute atrial
      fibrillation.

PMID- 28749902
TI  - Programmed death ligand 1 testing: is there one best test?

PMID- 28749903
TI  - Drug development for rare cancers in children.

PMID- 28749904
TI  - Use of genetic markers in multiple myeloma.

PMID- 28749905
TI  - The BALAD-2 and GALAD biomarker models for hepatocellular carcinoma.

PMID- 28749906
TI  - Locoregional therapy for liver metastases in colorectal cancer.

PMID- 28749907
TI  - Immunotherapy in urothelial cancer, part 1: T-cell checkpoint inhibition in
      advanced or metastatic disease.
AB  - Cancer of the urothelium is the sixth most common cancer in the United States and
      is seen predominantly in men. Most cases of this disease present as non-muscle
      invasive bladder cancer (NMIBC), with cancer recurrence or progression to muscle
      invasive cancer in more than 50% of patients after initial therapy. NMIBC is an
      immune-responsive disease, as indicated by the use of intravesical bacillus
      Calmette-Guerin as treatment for more than 3 decades. More recently,
      immunotherapy has seen much progress in a variety of cancers, including advanced
      and metastatic bladder cancer, in which historical 5-year survival rates are
      approximately 15%. The advent of T-cell checkpoint inhibitors, especially those
      directed at programmed death 1 (PD-1) and its ligand (PD-L1), has had a
      significant effect on the therapy of advanced urothelial cancer. This had led to
      accelerated approval by the US Food and Drug Administration for atezolizumab and
      nivolumab in advanced urothelial cancer previously treated with platinum-based
      chemotherapy. In addition, level 1 evidence supports the use of pembrolizumab
      over single-agent tubulin-directed chemotherapy in the same setting. Several
      other treatments with immune-mediating mechanisms of action are in development
      and hold great promise, including monoclonal antibodies directed at other
      checkpoint molecules, oncolytic virus therapy, adoptive T-cell therapy,
      combination immunotherapy, and antibody-drug conjugates. This review focuses on
      the recent development of T-cell checkpoint inhibitors in advanced and metastatic
      urothelial cancer and addresses their potential use in combination. It also
      discusses a spectrum of novel immunotherapies with potential use in urothelial
      cancer.

PMID- 28749908
TI  - Combined blockade of vascular endothelial growth factor and programmed death 1
      pathways in advanced kidney cancer.
AB  - Targeted and immune-based therapies have improved outcomes in advanced kidney
      cancer, yet novel strategies are needed to extend the duration of these benefits
      and expand them to more patients. Combined inhibition of vascular endothelial
      growth factor (VEGF) and the programmed death 1 (PD-1)/programmed death ligand 1
      (PD-L1) pathways with therapeutic agents already in clinical use may offer such a
      strategy. Here, we describe the development and clinical evaluation of VEGF
      inhibitors and, separately, PD-1/PD-L1 inhibitors. We present preclinical
      evidence of interaction between these pathways and the rationale for combined
      blockade. Beyond well-known effects on pathologic angiogenesis, VEGF blockade
      also may decrease immune tolerance and enhance PD-1/PD-L1 blockade. We conclude
      with the results of several early trials of combined VEGF and PD-1/PD-L1
      blockade, which demonstrate encouraging antitumor activity, and we pose questions
      for future study.

PMID- 28749909
TI  - Yes, treatment for CML should continue indefinitely.

PMID- 28749910
TI  - No, treatment for CML should not continue indefinitely.

PMID- 28749912
TI  - Which patients with early-stage triple-negative breast cancer should receive a
      platinum?

PMID- 28749913
TI  - New insights into cytomegalovirus infection after allogeneic hematopoietic stem
      cell transplant.

PMID- 28749914
TI  - Identifying patients with leukemia who are at risk for fungal infections.

PMID- 28749916
TI  - Highlights in kidney cancer from the American Society of Clinical Oncology
      Genitourinary Cancers Symposium.

PMID- 28749917
TI  - The microbiome: a basis for novel immunomodulation in mice and men.

PMID- 28749918
TI  - Immunotherapy in urothelial cancer, part 2: adjuvant, neoadjuvant, and adjunctive
      treatment.
AB  - Urothelial cancer, which is predominantly seen in men, is common throughout the
      world. Most disease presents as non-muscle invasive bladder cancer (NMIBC), with
      cancer recurring or progressing to muscle invasive disease in more than 50% of
      patients after initial therapy. NMIBC is an immune responsive disease, as
      indicated by the use of intravesical bacillus Calmette-Guerin as treatment for
      more than 3 decades. The advent of T-cell checkpoint inhibitors, especially those
      directed at programmed death 1 (PD-1) and its ligand (PD-L1), has had a
      significant impact on the therapy of advanced urothelial cancer. This had led to
      a revisitation of immunotherapy in urothelial cancer, as well as the genesis of
      trials using novel immunotherapeutic agents. This review focuses on immunotherapy
      in NMIBC, both on its own and as a potential treatment in combination with RT. It
      also discusses the development of immunotherapies in early bladder cancer disease
      states, and in neoadjuvant and adjuvant perioperative settings for localized
      muscle invasive cancers.

PMID- 28749919
TI  - Philadelphia chromosome-like acute lymphoblastic leukemia: progress in a new
      cancer subtype.
AB  - Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a
      newly described, high-risk subtype of B-cell ALL. It is characterized by a gene
      expression profile similar to that of Ph-positive ALL; however, the BCR-ABL1
      fusion is not present. The World Health Organization classification of myeloid
      neoplasms and acute leukemia recently was updated to include the Ph-like or BCR
      ABL1-like ALL subtype of B-cell ALL as a provisional entity. Unlike Ph-positive
      ALL, which is characterized by the pathognomonic BCR-ABL1 fusion, Ph-like ALL is
      characterized by a multitude of different genetic rearrangements and mutations.
      In this review, we outline the age-related and geographic incidence of Ph-like
      ALL, the association with worse clinical outcomes, and early evidence for the use
      of ruxolitinib (a Janus kinase 2 inhibitor) and dasatinib (a tyrosine kinase
      inhibitor targeting ABL1).

PMID- 28749920
TI  - Announcement: Monitoring Selected National HIV Prevention and Care Objectives.
AB  - CDC monitors progress on selected national human immunodeficiency virus (HIV)
      prevention and care objectives using surveillance data (1) and has released two
      HIV care continuums for 2014: a diagnosis-based continuum and a prevalence-based
      continuum (2,3).

PMID- 28749921
TI  - Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with
      Possible Zika Virus Exposure - United States (Including U.S. Territories), July
      2017.
AB  - CDC has updated the interim guidance for U.S. health care providers caring for
      pregnant women with possible Zika virus exposure in response to 1) declining
      prevalence of Zika virus disease in the World Health Organization's Region of the
      Americas (Americas) and 2) emerging evidence indicating prolonged detection of
      Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first
      reported in the Americas during 2015-2016; however, the incidence of Zika virus
      disease has since declined. As the prevalence of Zika virus disease declines, the
      likelihood of false-positive test results increases. In addition, emerging
      epidemiologic and laboratory data indicate that, as is the case with other
      flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after
      infection. Therefore, IgM test results cannot always reliably distinguish between
      an infection that occurred during the current pregnancy and one that occurred
      before the current pregnancy, particularly for women with possible Zika virus
      exposure before the current pregnancy. These limitations should be considered
      when counseling pregnant women about the risks and benefits of testing for Zika
      virus infection during pregnancy. This updated guidance emphasizes a shared
      decision-making model for testing and screening pregnant women, one in which
      patients and providers work together to make decisions about testing and care
      plans based on patient preferences and values, clinical judgment, and a balanced
      assessment of risks and expected outcomes.

PMID- 28749923
TI  - QuickStats: Age-Adjusted Percentage* of Adults Aged >=18 Years Who Were Never in
      Pain, in Pain Some Days, or in Pain Most Days or Every Day in the Past 6 Months,?
      by Employment StatusS - National Health Interview Survey,  United States, 2016.

PMID- 28749922
TI  - Outbreak of Septic Arthritis Associated with Intra-Articular Injections at an
      Outpatient Practice - New Jersey, 2017.
AB  - On March 6, 2017, the New Jersey Department of Health (NJDOH) was notified of
      three cases of septic arthritis in patients who had received intra-articular
      injections for osteoarthritic knee pain at a private outpatient practice. The
      practice voluntarily closed the next day. NJDOH, in conjunction with the local
      health department and the New Jersey Board of Medical Examiners, conducted an
      investigation and identified 41 cases of septic arthritis associated with intra
      articular injections administered during 250 patient visits at the same practice,
      including 30 (73%) patients who required surgery. Bacterial cultures of synovial
      fluid or tissue from 15 (37%) patients were positive; all recovered organisms
      were oral flora. An infection prevention assessment of the practice identified
      multiple breaches of recommended infection prevention practices, including
      inadequate hand hygiene, inappropriate use of pharmacy bulk packaged (PBP)
      products as multiple-dose containers and handling PBP products outside of
      required pharmacy conditions, and preparation of syringes up to 4 days in advance
      of their intended use. No additional septic arthritis cases were identified after
      infection prevention recommendations were implemented within the practice.

PMID- 28749924
TI  - Update: Temporary Total Depletion of U.S. Licensed Yellow Fever Vaccine for
      Civilian Travelers Addressed by Investigational New Drug Use of Imported Stamaril
      Vaccine.
AB  - Sanofi Pasteur, the manufacturer of the only yellow fever vaccine (YF-VAX)
      licensed in the United States, has announced that their stock of YF-VAX is
      totally depleted as of July 24, 2017. YF-VAX for civilian use will be unavailable
      for ordering from Sanofi Pasteur until mid-2018, when their new manufacturing
      facility is expected to be completed. However, YF-VAX might be available at some
      clinics for several months, until remaining supplies at those sites are
      exhausted. In anticipation of this temporary total depletion, in 2016, Sanofi
      Pasteur submitted an expanded access investigational new drug application to the
      Food and Drug Administration to allow for importation and use of Stamaril. The
      Food and Drug Administration accepted Sanofi Pasteur's application in October
      2016.

PMID- 28749926
TI  - Erratum: Vol. 66, No. 18.
AB  - In the report "State HCV Incidence and Policies Related to HCV Preventive and
      Treatment Services for Persons Who Inject Drugs - United States, 2015-2016," on
      page 466, the second sentence of the second paragraph should have read "HCV
      incidence rates increased by 167% nationally from 0.3 cases per 100,000 U.S.
      population in 2010 to 0.8 in 2015 (4)."

PMID- 28749925
TI  - The Role of Screening and Treatment in National Progress Toward Hepatitis C
      Elimination - Georgia, 2015-2016.
AB  - Georgia, a country in the Caucasus region of Eurasia, has a high prevalence of
      hepatitis C virus (HCV) infection. In April 2015, with technical assistance from
      CDC, Georgia embarked on the world's first program to eliminate hepatitis C,
      defined as a 90% reduction in HCV prevalence by 2020 (1,2). The country committed
      to identifying infected persons and linking them to care and curative antiviral
      therapy, which was provided free of charge through a partnership with Gilead
      Sciences (1,2). From April 2015 through December 2016, a total of 27,595 persons
      initiated treatment for HCV infection, among whom 19,778 (71.7%) completed
      treatment. Among 6,366 persons tested for HCV RNA >=12 weeks after completing
      treatment, 5,356 (84.1%) had no detectable virus in their blood, indicative of a
      sustained virologic response (SVR) and cure of HCV infection. The number of
      persons initiating treatment peaked in September 2016 at 4,595 and declined
      during October-December. Broader implementation of interventions that increase
      access to HCV testing, care, and treatment for persons living with HCV are needed
      for Georgia to reach national targets for the elimination of HCV.

PMID- 28749927
TI  - CDC Grand Rounds: Addressing Health Disparities in Early Childhood.
AB  - Research suggests that many disparities in overall health and well-being are
      rooted in early childhood (1,2). Stressors in early childhood can disrupt
      neurologic, metabolic, and immunologic systems, leading to poorer developmental
      outcomes (1). However, consistent, responsive caregiving relationships and
      supportive community and health care environments promote an optimal trajectory
      (3,4). The first 8 years of a child's life build a foundation for future health
      and life success (5-7). Thus, the cumulative and lifelong impact of early
      experiences, both positive and negative, on a child's development can be
      profound. Although the health, social service, and education systems that serve
      young children and their families and communities provide opportunities to
      support responsive relationships and environments, efforts by these systems are
      often fragmented because of restrictions that limit the age groups they can serve
      and types of services they can provide. Integrating relationship-based prevention
      and intervention services for children early in life, when the brain is
      developing most rapidly, can optimize developmental trajectories (4,7). By
      promoting collaboration and data-driven intervention activities, public health
      can play a critical role in both the identification of at-risk children and the
      integration of systems that can support healthy development. These efforts can
      address disparities by reducing barriers that might prevent children from
      reaching their full potential.

PMID- 28749928
TI  - Corrigendum: On the Thermal and Thermodynamic (In)Stability of Methylammonium
      Lead Halide Perovskites.
AB  - This corrects the article DOI: 10.1038/srep31896.

PMID- 28749929
TI  - Chemoenzymatic synthesis of glycoengineered IgG antibodies and glycosite-specific
      antibody-drug conjugates.
AB  - Glycoengineered therapeutic antibodies and glycosite-specific antibody-drug
      conjugates (gsADCs) have generated great interest among researchers because of
      their therapeutic potential. Endoglycosidase-catalyzed in vitro glycoengineering
      technology is a powerful tool for IgG Fc (fragment cystallizable) N-glycosylation
      remodeling. In this protocol, native heterogeneously glycosylated IgG N-glycans
      are first deglycosylated with a wild-type endoglycosidase. Next, a homogeneous N
      glycan substrate, presynthesized as described here, is attached to the remaining
      N-acetylglucosamine (GlcNAc) of IgG, using a mutant endoglycosidase (also called
      endoglycosynthase) that lacks hydrolytic activity but possesses
      transglycosylation activity for glycoengineering. Compared with in vivo
      glycoengineering technologies and the glycosyltransferase-enabled in vitro
      engineering method, the current approach is robust and features quantitative
      yield, homogeneous glycoforms of produced antibodies and ADCs, compatibility with
      diverse natural and non-natural glycan structures, convenient exploitation of
      native IgG as the starting material, and a well-defined conjugation site for
      antibody modifications. Potential applications of this method cover a broad scope
      of antibody-related research, including the development of novel glycoengineered
      therapeutic antibodies with enhanced efficacy, site-specific antibody-drug
      conjugation, and site-specific modification of antibodies for fluorescent
      labeling, PEGylation, protein cross-linking, immunoliposome formation, and so on,
      without loss of antigen-binding affinity. It takes 5-8 d to prepare the natural
      or modified N-glycan substrates, 3-4 d to engineer the IgG N-glycosylation, and 2
      5 d to synthesize the small-molecule toxins and prepare the gsADCs.

PMID- 28749930
TI  - Nontargeted virus sequence discovery pipeline and virus clustering for
      metagenomic data.
AB  - The analysis of large microbiome data sets holds great promise for the
      delineation of the biological and metabolic functioning of living organisms and
      their role in the environment. In the midst of this genomic puzzle, viruses,
      especially those that infect microbial communities, represent a major reservoir
      of genetic diversity with great impact on biogeochemical cycles and organismal
      health. Overcoming the limitations associated with virus detection directly from
      microbiomes can provide key insights into how ecosystem dynamics are modulated.
      Here, we present a computational protocol for accurate detection and grouping of
      viral sequences from microbiome samples. Our approach relies on an expanded and
      curated set of viral protein families used as bait to identify viral sequences
      directly from metagenomic assemblies. This protocol describes how to use the
      viral protein families catalog (~7 h) and recommended filters for the detection
      of viral contigs in metagenomic samples (~6 h), and it describes the specific
      parameters for a nucleotide-sequence-identity-based method of organizing the
      viral sequences into quasi-species taxonomic-level groups (~10 min).

PMID- 28749931
TI  - Quantitative, multiplexed workflow for deep analysis of human blood plasma and
      biomarker discovery by mass spectrometry.
AB  - Proteomic characterization of blood plasma is of central importance to clinical
      proteomics and particularly to biomarker discovery studies. The vast dynamic
      range and high complexity of the plasma proteome have, however, proven to be
      serious challenges and have often led to unacceptable tradeoffs between depth of
      coverage and sample throughput. We present an optimized sample-processing
      pipeline for analysis of the human plasma proteome that provides greatly
      increased depth of detection, improved quantitative precision and much higher
      sample analysis throughput as compared with prior methods. The process includes
      abundant protein depletion, isobaric labeling at the peptide level for
      multiplexed relative quantification and ultra-high-performance liquid
      chromatography coupled to accurate-mass, high-resolution tandem mass spectrometry
      analysis of peptides fractionated off-line by basic pH reversed-phase (bRP)
      chromatography. The overall reproducibility of the process, including
      immunoaffinity depletion, is high, with a process replicate coefficient of
      variation (CV) of <12%. Using isobaric tags for relative and absolute
      quantitation (iTRAQ) 4-plex, >4,500 proteins are detected and quantified per
      patient sample on average, with two or more peptides per protein and starting
      from as little as 200 MUl of plasma. The approach can be multiplexed up to 10
      plex using tandem mass tags (TMT) reagents, further increasing throughput, albeit
      with some decrease in the number of proteins quantified. In addition, we provide
      a rapid protocol for analysis of nonfractionated depleted plasma samples analyzed
      in 10-plex. This provides ~600 quantified proteins for each of the ten samples in
      ~5 h of instrument time.

PMID- 28749932
TI  - Corrigendum: Pentose sugars inhibit metabolism and increase expression of an AgrD
      type cyclic pentapeptide in Clostridium thermocellum.
AB  - This corrects the article DOI: 10.1038/srep43355.

PMID- 28749933
TI  - Participation of women and children in hunting activities in Sierra Leone and
      implications for control of zoonotic infections.
AB  - The emergence of infectious diseases of zoonotic origin highlights the need to
      understand social practices at the animal-human interface. This study provides a
      qualitative account of interactions between humans and wild animals in
      predominantly Mende villages of southern Sierra Leone. We conducted fieldwork
      over 4 months including participant and direct observations, semi-structured
      interviews (n = 47), spontaneously occurring focus group discussions (n = 12),
      school essays and informal interviews to describe behaviours that may serve as
      pathways for zoonotic infection. In this region, hunting is the primary form of
      contact with wild animals. We describe how these interactions are shaped by socio
      cultural contexts, including opportunities to access economic resources and by
      social obligations and constraints. Our research suggests that the potential for
      exposure to zoonotic pathogens is more widely distributed across different age,
      gender and social groups than previously appreciated. We highlight the role of
      children in hunting, an age group that has previously not been discussed in the
      context of hunting. The breadth of the "at risk" population forces
      reconsideration of how we conceptualize, trace and monitor pathogen exposure.

PMID- 28749934
TI  - The population genomics of archaeological transition in west Iberia:
      Investigation of ancient substructure using imputation and haplotype-based
      methods.
AB  - We analyse new genomic data (0.05-2.95x) from 14 ancient individuals from
      Portugal distributed from the Middle Neolithic (4200-3500 BC) to the Middle
      Bronze Age (1740-1430 BC) and impute genomewide diploid genotypes in these
      together with published ancient Eurasians. While discontinuity is evident in the
      transition to agriculture across the region, sensitive haplotype-based analyses
      suggest a significant degree of local hunter-gatherer contribution to later
      Iberian Neolithic populations. A more subtle genetic influx is also apparent in
      the Bronze Age, detectable from analyses including haplotype sharing with both
      ancient and modern genomes, D-statistics and Y-chromosome lineages. However, the
      limited nature of this introgression contrasts with the major Steppe migration
      turnovers within third Millennium northern Europe and echoes the survival of non
      Indo-European language in Iberia. Changes in genomic estimates of individual
      height across Europe are also associated with these major cultural transitions,
      and ancestral components continue to correlate with modern differences in
      stature.

PMID- 28749935
TI  - Growth of bacteria in 3-d colonies.
AB  - The dynamics of growth of bacterial populations has been extensively studied for
      planktonic cells in well-agitated liquid culture, in which all cells have equal
      access to nutrients. In the real world, bacteria are more likely to live in
      physically structured habitats as colonies, within which individual cells vary in
      their access to nutrients. The dynamics of bacterial growth in such conditions is
      poorly understood, and, unlike that for liquid culture, there is not a standard
      broadly used mathematical model for bacterial populations growing in colonies in
      three dimensions (3-d). By extending the classic Monod model of resource-limited
      population growth to allow for spatial heterogeneity in the bacterial access to
      nutrients, we develop a 3-d model of colonies, in which bacteria consume
      diffusing nutrients in their vicinity. By following the changes in density of E.
      coli in liquid and embedded in glucose-limited soft agar, we evaluate the fit of
      this model to experimental data. The model accounts for the experimentally
      observed presence of a sub-exponential, diffusion-limited growth regime in
      colonies, which is absent in liquid cultures. The model predicts and our
      experiments confirm that, as a consequence of inter-colony competition for the
      diffusing nutrients and of cell death, there is a non-monotonic relationship
      between total number of colonies within the habitat and the total number of
      individual cells in all of these colonies. This combined theoretical-experimental
      study reveals that, within 3-d colonies, E. coli cells are loosely packed, and
      colonies produce about 2.5 times as many cells as the liquid culture from the
      same amount of nutrients. We verify that this is because cells in liquid culture
      are larger than in colonies. Our model provides a baseline description of
      bacterial growth in 3-d, deviations from which can be used to identify phenotypic
      heterogeneities and inter-cellular interactions that further contribute to the
      structure of bacterial communities.

PMID- 28749936
TI  - MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and
      non-seed interaction with TFAP2A transcript to attenuate NSCLC growth.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs, which direct post
      transcriptional gene silencing (PTGS) and function in a vast range of biological
      events including cancer development. Most miRNAs pair to the target sites through
      seed region near the 5' end, leading to mRNA cleavage and/or translation
      repression. Here, we demonstrated a miRNA-induced dual regulation of heme
      oxygenase-1 (HO-1) via seed region and non-seed region, consequently inhibited
      tumor growth of NSCLC. We identified miR-1254 as a negative regulator inhibiting
      HO-1 translation by directly targeting HO-1 3'UTR via its seed region, and
      suppressing HO-1 transcription via non-seed region-dependent inhibition of
      transcriptional factor AP-2 alpha (TFAP2A), a transcriptional activator of HO-1.
      MiR-1254 induced cell apoptosis and cell cycle arrest in human non-small cell
      lung carcinoma (NSCLC) cells by inhibiting the expression of HO-1, consequently
      suppressed NSCLC cell growth. Consistently with the in vitro studies, mouse
      xenograft studies validated that miR-1254 suppressed NSCLC tumor growth in vivo.
      Moreover, we found that HO-1 expression was inversely correlated with miR-1254
      level in human NSCLC tumor samples and cell lines. Overall, these findings
      identify the dual inhibition of HO-1 by miR-1254 as a novel functional mechanism
      of miRNA, which results in a more effective inhibition of oncogenic mRNA, and
      leads to a tumor suppressive effect.

PMID- 28749937
TI  - Recurrently connected and localized neuronal communities initiate coordinated
      spontaneous activity in neuronal networks.
AB  - Developing neuronal systems intrinsically generate coordinated spontaneous
      activity that propagates by involving a large number of synchronously firing
      neurons. In vivo, waves of spikes transiently characterize the activity of
      developing brain circuits and are fundamental for activity-dependent circuit
      formation. In vitro, coordinated spontaneous spiking activity, or network bursts
      (NBs), interleaved within periods of asynchronous spikes emerge during the
      development of 2D and 3D neuronal cultures. Several studies have investigated
      this type of activity and its dynamics, but how a neuronal system generates these
      coordinated events remains unclear. Here, we investigate at a cellular level the
      generation of network bursts in spontaneously active neuronal cultures by
      exploiting high-resolution multielectrode array recordings and computational
      network modelling. Our analysis reveals that NBs are generated in specialized
      regions of the network (functional neuronal communities) that feature neuronal
      links with high cross-correlation peak values, sub-millisecond lags and that
      share very similar structural connectivity motifs providing recurrent
      interactions. We show that the particular properties of these local structures
      enable locally amplifying spontaneous asynchronous spikes and that this mechanism
      can lead to the initiation of NBs. Through the analysis of simulated and
      experimental data, we also show that AMPA currents drive the coordinated
      activity, while NMDA and GABA currents are only involved in shaping the dynamics
      of NBs. Overall, our results suggest that the presence of functional neuronal
      communities with recurrent local connections allows a neuronal system to generate
      spontaneous coordinated spiking activity events. As suggested by the rules used
      for implementing our computational model, such functional communities might
      naturally emerge during network development by following simple constraints on
      distance-based connectivity.

PMID- 28749938
TI  - The mecillinam resistome reveals a role for peptidoglycan endopeptidases in
      stimulating cell wall synthesis in Escherichia coli.
AB  - Bacterial cells are typically surrounded by an net-like macromolecule called the
      cell wall constructed from the heteropolymer peptidoglycan (PG). Biogenesis of
      this matrix is the target of penicillin and related beta-lactams. These drugs
      inhibit the transpeptidase activity of PG synthases called penicillin-binding
      proteins (PBPs), preventing the crosslinking of nascent wall material into the
      existing network. The beta-lactam mecillinam specifically targets the PBP2 enzyme
      in the cell elongation machinery of Escherichia coli. Low-throughput selections
      for mecillinam resistance have historically been useful in defining mechanisms
      involved in cell wall biogenesis and the killing activity of beta-lactam
      antibiotics. Here, we used transposon-sequencing (Tn-Seq) as a high-throughput
      method to identify nearly all mecillinam resistance loci in the E. coli genome,
      providing a comprehensive resource for uncovering new mechanisms underlying PG
      assembly and drug resistance. Induction of the stringent response or the Rcs
      envelope stress response has been previously implicated in mecillinam resistance.
      We therefore also performed the Tn-Seq analysis in mutants defective for these
      responses in addition to wild-type cells. Thus, the utility of the dataset was
      greatly enhanced by determining the stress response dependence of each resistance
      locus in the resistome. Reasoning that stress response-independent resistance
      loci are those most likely to identify direct modulators of cell wall biogenesis,
      we focused our downstream analysis on this subset of the resistome.
      Characterization of one of these alleles led to the surprising discovery that the
      overproduction of endopeptidase enzymes that cleave crosslinks in the cell wall
      promotes mecillinam resistance by stimulating PG synthesis by a subset of PBPs.
      Our analysis of this activation mechanism suggests that, contrary to the
      prevailing view in the field, PG synthases and PG cleaving enzymes need not
      function in multi-enzyme complexes to expand the cell wall matrix.

PMID- 28749939
TI  - A novel rapid test for detecting antibody responses to Loa loa infections.
AB  - Ivermectin-based mass drug administration (MDA) programs have achieved remarkable
      success towards the elimination of onchocerciasis and lymphatic filariasis.
      However, their full implementation has been hindered in Central Africa by the
      occurrence of ivermectin-related severe adverse events (SAEs) in a subset of
      individuals with high circulating levels of Loa loa microfilariae. Extending MDA
      to areas with coincident L. loa infection is problematic, and inexpensive point
      of-care tests for L. loa are acutely needed. Herein, we present a lateral flow
      assay (LFA) to identify subjects with a serological response to Ll-SXP-1, a
      specific and validated marker of L. loa. The test was evaluated on serum samples
      from patients infected with L. loa (n = 109) and other helminths (n = 204), as
      well as on uninfected controls (n = 77). When read with the naked eye, the test
      was 94% sensitive for L. loa infection and was 100% specific when sera from
      healthy endemic and non-endemic controls or from those with S. stercoralis
      infections were used as the comparators. When sera of patients with O. volvulus,
      W. bancrofti, or M. perstans were used as the comparators, the specificity of the
      LFA was 82%, 87%, and 88%, respectively. A companion smartphone reader allowed
      measurement of the test line intensities and establishment of cutoff values. With
      a cutoff of 600 Units, the assay sensitivity decreased to 71%, but the
      specificity increased to 96% for O. volvulus, 100% for W. bancrofti, and 100% for
      M. perstans-infected individuals. The LFA may find applications in refining the
      current maps of L. loa prevalence, which are needed to eliminate onchocerciasis
      and lymphatic filariasis from the African continent.

PMID- 28749940
TI  - Upregulation of an inward rectifying K+ channel can rescue slow Ca2+ oscillations
      in K(ATP) channel deficient pancreatic islets.
AB  - Plasma insulin oscillations are known to have physiological importance in the
      regulation of blood glucose. In insulin-secreting beta-cells of pancreatic
      islets, K(ATP) channels play a key role in regulating glucose-dependent insulin
      secretion. In addition, they convey oscillations in cellular metabolism to the
      membrane by sensing adenine nucleotides, and are thus instrumental in mediating
      pulsatile insulin secretion. Blocking K(ATP) channels pharmacologically
      depolarizes the beta-cell plasma membrane and terminates islet oscillations.
      Surprisingly, when K(ATP) channels are genetically knocked out, oscillations in
      islet activity persist, and relatively normal blood glucose levels are
      maintained. Compensation must therefore occur to overcome the loss of K(ATP)
      channels in K(ATP) knockout mice. In a companion study, we demonstrated a
      substantial increase in Kir2.1 protein occurs in beta-cells lacking K(ATP)
      because of SUR1 deletion. In this report, we demonstrate that beta-cells of SUR1
      null islets have an upregulated inward rectifying K+ current that helps to
      compensate for the loss of K(ATP) channels. This current is likely due to the
      increased expression of Kir2.1 channels. We used mathematical modeling to
      determine whether an ionic current having the biophysical characteristics of
      Kir2.1 is capable of rescuing oscillations that are similar in period to those of
      wild-type islets. By experimentally testing a key model prediction we suggest
      that Kir2.1 current upregulation is a likely mechanism for rescuing the
      oscillations seen in islets from mice deficient in K(ATP) channels.

PMID- 28749941
TI  - Krox20 hindbrain regulation incorporates multiple modes of cooperation between
      cis-acting elements.
AB  - Developmental genes can harbour multiple transcriptional enhancers that act
      simultaneously or in succession to achieve robust and precise spatiotemporal
      expression. However, the mechanisms underlying cooperation between cis-acting
      elements are poorly documented, notably in vertebrates. The mouse gene Krox20
      encodes a transcription factor required for the specification of two segments
      (rhombomeres) of the developing hindbrain. In rhombomere 3, Krox20 is subject to
      direct positive feedback governed by an autoregulatory enhancer, element A. In
      contrast, a second enhancer, element C, distant by 70 kb, is active from the
      initiation of transcription independent of the presence of the KROX20 protein.
      Here, using both enhancer knock-outs and investigations of chromatin
      organisation, we show that element C possesses a dual activity: besides its
      classical enhancer function, it is also permanently required in cis to potentiate
      the autoregulatory activity of element A, by increasing its chromatin
      accessibility. This work uncovers a novel, asymmetrical, long-range mode of
      cooperation between cis-acting elements that might be essential to avoid
      promiscuous activation of positive autoregulatory elements.

PMID- 28749942
TI  - Aedes aegypti control in urban areas: A systemic approach to a complex dynamic.
AB  - The available strategy for controlling the diseases transmitted by Aedes aegypti
      (dengue fever, Zika, and chikungunya) relies on continued community
      participation. Despite slogans emphasizing how easy it should be, no country has
      achieved it since the seventies. To better investigate potentially sustainable
      interventions, we developed a systemic model based on a multidisciplinary
      approach, integrating as deeply as possible specialized knowledge and field
      experience. The resulting model is composed of 4 external and 8 internal
      subsystems and 31 relationships, consistent with the literature and checked over
      multiple iterations with specialists of the many areas. We analyzed the model and
      the main feedback loops responsible for the system's stability, searching for
      possible interventions that could shift the existing balance. We suggest the
      introduction of 1 more player, the local primary health care structure, with the
      potential to change the undesired equilibrium. The health agents in the areas are
      the first to detect disease cases, and they could stimulate individuals to inform
      about potential mosquitoes' breeding sites and bring timely information to the
      vector-control program. Triggering such an action could introduce changes in
      people's attitude through a positive feedback loop in the desired direction.

PMID- 28749943
TI  - Integrated time-lapse and single-cell transcription studies highlight the
      variable and dynamic nature of human hematopoietic cell fate commitment.
AB  - Individual cells take lineage commitment decisions in a way that is not
      necessarily uniform. We address this issue by characterising transcriptional
      changes in cord blood-derived CD34+ cells at the single-cell level and
      integrating data with cell division history and morphological changes determined
      by time-lapse microscopy. We show that major transcriptional changes leading to a
      multilineage-primed gene expression state occur very rapidly during the first
      cell cycle. One of the 2 stable lineage-primed patterns emerges gradually in each
      cell with variable timing. Some cells reach a stable morphology and molecular
      phenotype by the end of the first cell cycle and transmit it clonally. Others
      fluctuate between the 2 phenotypes over several cell cycles. Our analysis
      highlights the dynamic nature and variable timing of cell fate commitment in
      hematopoietic cells, links the gene expression pattern to cell morphology, and
      identifies a new category of cells with fluctuating phenotypic characteristics,
      demonstrating the complexity of the fate decision process (which is different
      from a simple binary switch between 2 options, as it is usually envisioned).

PMID- 28749944
TI  - Mode of birth and medical interventions among women at low risk of complications:
      A cross-national comparison of birth settings in England and the Netherlands.
AB  - OBJECTIVES: To compare mode of birth and medical interventions between broadly
      equivalent birth settings in England and the Netherlands. METHODS: Data were
      combined from the Birthplace study in England (from April 2008 to April 2010) and
      the National Perinatal Register in the Netherlands (2009). Low risk women in
      England planning birth at home (16,470) or in freestanding midwifery units
      (11,133) were compared with Dutch women with planned home births (40,468). Low
      risk English women with births planned in alongside midwifery units (16,418) or
      obstetric units (19,096) were compared with Dutch women with planned midwife-led
      hospital births (37,887). RESULTS: CS rates varied across planned births settings
      from 6.5% to 15.5% among nulliparous and 0.6% to 5.1% among multiparous women. CS
      rates were higher among low risk nulliparous and multiparous English women
      planning obstetric unit births compared to Dutch women planning midwife-led
      hospital births (adjusted (adj) OR 1.89 (95% CI 1.64 to 2.18) and 3.66 (2.90 to
      4.63) respectively). Instrumental vaginal birth rates varied from 10.7% to 22.5%
      for nulliparous and from 0.9% to 5.7% for multiparous women. Rates were lower in
      the English comparison groups apart from planned births in obstetric units.
      Transfer, augmentation and episiotomy rates were much lower in England compared
      to the Netherlands for all midwife-led groups. In most comparisons, epidural
      rates were higher among English groups. CONCLUSIONS: When considering maternal
      outcomes, findings confirm advantages of giving birth in midwife-led settings for
      low risk women. Further research is needed into strategies to decrease rates of
      medical intervention in obstetric units in England and to reduce rates of
      avoidable transfer, episiotomy and augmentation of labour in the Netherlands.

PMID- 28749945
TI  - Quantitative computed tomography determined regional lung mechanics in normal
      nonsmokers, normal smokers and metastatic sarcoma subjects.
AB  - OBJECTIVES: Extra-thoracic tumors send out pilot cells that attach to the
      pulmonary endothelium. We hypothesized that this could alter regional lung
      mechanics (tissue stiffening or accumulation of fluid and inflammatory cells)
      through interactions with host cells. We explored this with serial inspiratory
      computed tomography (CT) and image matching to assess regional changes in lung
      expansion. MATERIALS AND METHODS: We retrospectively assessed 44 pairs of two
      serial CT scans on 21 sarcoma patients: 12 without lung metastases and 9 with
      lung metastases. For each subject, two or more serial inspiratory clinically
      derived CT scans were retrospectively collected. Two research-derived control
      groups were included: 7 normal nonsmokers and 12 asymptomatic smokers with two
      inspiratory scans taken the same day or one year apart respectively. We performed
      image registration for local-to-local matching scans to baseline, and derived
      local expansion and density changes at an acinar scale. Welch two sample t test
      was used for comparison between groups. Statistical significance was determined
      with a p value < 0.05. RESULTS: Lung regions of metastatic sarcoma patients (but
      not the normal control group) demonstrated an increased proportion of normalized
      lung expansion between the first and second CT. These hyper-expanded regions were
      associated with, but not limited to, visible metastatic lung lesions. Compared
      with the normal control group, the percent of increased normalized hyper-expanded
      lung in sarcoma subjects was significantly increased (p < 0.05). There was also
      evidence of increased lung "tissue" volume (non-air components) in the hyper
      expanded regions of the cancer subjects relative to non-hyper-expanded regions.
      "Tissue" volume increase was present in the hyper-expanded regions of metastatic
      and non-metastatic sarcoma subjects. This putatively could represent regional
      inflammation related to the presence of tumor pilot cell-host related
      interactions. CONCLUSIONS: This new quantitative CT (QCT) method for linking
      serial acquired inspiratory CT images may provide a diagnostic and prognostic
      means to objectively characterize regional responses in the lung following
      oncological treatment and monitoring for lung metastases.

PMID- 28749946
TI  - Genome-wide association analysis identifies genetic correlates of immune
      infiltrates in solid tumors.
AB  - Therapeutic options for the treatment of an increasing variety of cancers have
      been expanded by the introduction of a new class of drugs, commonly referred to
      as checkpoint blocking agents, that target the host immune system to positively
      modulate anti-tumor immune response. Although efficacy of these agents has been
      linked to a pre-existing level of tumor immune infiltrate, it remains unclear why
      some patients exhibit deep and durable responses to these agents while others do
      not benefit. To examine the influence of tumor genetics on tumor immune state, we
      interrogated the relationship between somatic mutation and copy number alteration
      with infiltration levels of 7 immune cell types across 40 tumor cohorts in The
      Cancer Genome Atlas. Levels of cytotoxic T, regulatory T, total T, natural
      killer, and B cells, as well as monocytes and M2 macrophages, were estimated
      using a novel set of transcriptional signatures that were designed to resist
      interference from the cellular heterogeneity of tumors. Tumor mutational load and
      estimates of tumor purity were included in our association models to adjust for
      biases in multi-modal genomic data. Copy number alterations, mutations summarized
      at the gene level, and position-specific mutations were evaluated for association
      with tumor immune infiltration. We observed a strong relationship between copy
      number loss of a large region of chromosome 9p and decreased lymphocyte estimates
      in melanoma, pancreatic, and head/neck cancers. Mutations in the oncogenes
      PIK3CA, FGFR3, and RAS/RAF family members, as well as the tumor suppressor TP53,
      were linked to changes in immune infiltration, usually in restricted tumor types.
      Associations of specific WNT/beta-catenin pathway genetic changes with immune
      state were limited, but we noted a link between 9p loss and the expression of the
      WNT receptor FZD3, suggesting that there are interactions between 9p alteration
      and WNT pathways. Finally, two different cell death regulators, CASP8 and DIDO1,
      were often mutated in head/neck tumors that had higher lymphocyte infiltrates. In
      summary, our study supports the relevance of tumor genetics to questions of
      efficacy and resistance in checkpoint blockade therapies. It also highlights the
      need to assess genome-wide influences during exploration of any specific tumor
      pathway hypothesized to be relevant to therapeutic response. Some of the observed
      genetic links to immune state, like 9p loss, may influence response to cancer
      immune therapies. Others, like mutations in cell death pathways, may help guide
      combination therapeutic approaches.

PMID- 28749947
TI  - The mediating role of recovery opportunities on future sickness absence from a
      gender- and age-sensitive perspective.
AB  - A lack of sufficient recovery during and after work may help to explain impaired
      health in the long run. We aimed to increase knowledge on the mediating role of
      recovery opportunities (RO) during and after work on future sickness absence from
      a gender- and age-sensitive perspective. We used data on RO from a Swedish
      national survey in 2011 and linked these to sickness absence (>14 days) two years
      later among the general working population (N = 7,649). Mediation of the
      relationship between gender and sickness absence by exposure to RO was studied
      through linear regression. We conducted separate analyses for RO during and after
      work and for three different age groups (16-29; 30-49; 50-64). The sample
      consisted of 3,563 men and 4,086 women. Sickness absence was higher among the
      women than among the men (11 days vs 5 days, p<0.001). Men reported statistically
      significantly more positive on their RO than women. RO during (beta 0.3-1.8) and
      after work (beta 0.4-0.6) mediated the relationship between gender and sickness
      absence. Mediation effects existed across age groups, with the strongest effects
      of RO during work found among the age group between 50 and 64 years of age
      (attenuation 36%). Our results indicate that gender inequality is also reflected
      in worse RO among women. This partially explains the increased risk of future
      sickness absence, particularly among those above 50 years of age. These findings
      show that RO during work deserve more attention in working life research.

PMID- 28749948
TI  - Anemia: A significant cardiovascular mortality risk after ST-segment elevation
      myocardial infarction complicated by the comorbidities of hypertension and kidney
      disease.
AB  - BACKGROUND: The effect of anemia on patients with ST-segment elevation myocardial
      infarction (STEMI) remains a controversial issue. The aim of this study was to
      explore the effect of anemia on STEMI patients. METHODS AND RESULTS: From January
      2005 to December 2014, 1751 patients experienced STEMI checked serum hemoglobin
      initially before any administration of fluids or IV medications. 1751 patients
      then received primary percutaneous intervention immediately. A total of 1388
      patients were enrolled in the non-anemia group because their serum hemoglobin
      level was more than 13 g/L in males, and 12 g/L in females. A total of 363
      patients were enrolled in the anemia group because their serum hemoglobin level
      was less than 13 g/L in males, and 12 g/L in females. Higher incidences of major
      adverse cerebral cardiac events (22.9% vs. 33.8%; p<0.001) were also noted in the
      anemia group, and these were related to higher incidence of cardiovascular
      mortality (6.5% vs. 20.4%; p<0.001). A higher incidence of all-cause mortality
      (8.6% vs. 27.7%; p<0.001) was also noted in the anemia group. A Kaplan-Meier
      curve of one-year cardiovascular mortality showed significant differences between
      the non-anemia and anemia group in all patients (P<0.001), and the patients with
      hypertension (P<0.001), and chronic kidney disease (CKD) (P = 0.011). CONCLUSION:
      Anemia is a marker of an increased risk in one-year cardiovascular mortality in
      patients with STEMI. If the patients have comorbidities such as hypertension, or
      CKD, the effect of anemia is very significant.

PMID- 28749949
TI  - 2-aminoimidazoles potentiate beta-lactam antimicrobial activity against
      Mycobacterium tuberculosis by reducing beta-lactamase secretion and increasing
      cell envelope permeability.
AB  - There is an urgent need to develop new drug treatment strategies to control the
      global spread of drug-sensitive and multidrug-resistant Mycobacterium
      tuberculosis (M. tuberculosis). The beta-lactam class of antibiotics is among the
      safest and most widely prescribed antibiotics, but they are not effective against
      M. tuberculosis due to intrinsic resistance. This study shows that 2
      aminoimidazole (2-AI)-based small molecules potentiate beta-lactam antibiotics
      against M. tuberculosis. Active 2-AI compounds significantly reduced the minimal
      inhibitory and bactericidal concentrations of beta-lactams by increasing M.
      tuberculosis cell envelope permeability and decreasing protein secretion
      including beta-lactamase. Metabolic labeling and transcriptional profiling
      experiments revealed that 2-AI compounds impair mycolic acid biosynthesis, export
      and linkage to the mycobacterial envelope, counteracting an important defense
      mechanism reducing permeability to external agents. Additionally, other important
      constituents of the M. tuberculosis outer membrane including sulfolipid-1 and
      polyacyltrehalose were also less abundant in 2-AI treated bacilli. As a
      consequence of 2-AI treatment, M. tuberculosis displayed increased sensitivity to
      SDS, increased permeability to nucleic acid staining dyes, and rapid binding of
      cell wall targeting antibiotics. Transcriptional profiling analysis further
      confirmed that 2-AI induces transcriptional regulators associated with cell
      envelope stress. 2-AI based small molecules potentiate the antimicrobial activity
      of beta-lactams by a mechanism that is distinct from specific inhibitors of beta
      lactamase activity and therefore may have value as an adjunctive anti-TB
      treatment.

PMID- 28749950
TI  - The role of early language abilities on math skills among Chinese children.
AB  - BACKGROUND: The present study investigated the role of early language abilities
      in the development of math skills among Chinese K-3 students. About 2000 children
      in China, who were on average aged 6 years, were assessed for both informal math
      (e.g., basic number concepts such as counting objects) and formal math
      (calculations including addition and subtraction) skills, language abilities and
      nonverbal intelligence. METHODOLOGY: Correlation analysis showed that language
      abilities were more strongly associated with informal than formal math skills,
      and regression analyses revealed that children's language abilities could
      uniquely predict both informal and formal math skills with age, gender, and
      nonverbal intelligence controlled. Mediation analyses demonstrated that the
      relationship between children's language abilities and formal math skills was
      partially mediated by informal math skills. RESULTS: The current findings
      indicate 1) Children's language abilities are of strong predictive values for
      both informal and formal math skills; 2) Language abilities impacts formal math
      skills partially through the mediation of informal math skills.

PMID- 28749951
TI  - Vitamin D-deficient mice have more invasive urinary tract infection.
AB  - Vitamin D deficiency is a common health problem with consequences not limited to
      bone and calcium hemostasis. Low levels have also been linked to tuberculosis and
      other respiratory infections as well as autoimmune diseases. We have previously
      shown that supplementation with vitamin D can induce the antimicrobial peptide
      cathelicidin during ex vivo infection of human urinary bladder. In rodents,
      however, cathelicidin expression is not linked to vitamin D and therefore this
      vitamin D-related effect fighting bacterial invasion is not relevant. To
      determine if vitamin D had further protective mechanisms during urinary tract
      infections, we therefore used a mouse model. In vitamin D-deficient mice, we
      detected more intracellular bacterial communities in the urinary bladder, higher
      degree of bacterial spread to the upper urinary tract and a skewed cytokine
      response. Furthermore, we show that the vitamin D receptor was upregulated in the
      urinary bladder and translocated into the cell nucleus after E. coli infection.
      This study supports a more general role for vitamin D as a local immune response
      mediator in the urinary tract.

PMID- 28749952
TI  - An innovative way of thinking nuclear waste management - Neutron physics of a
      reactor directly operating on SNF.
AB  - A solution for the nuclear waste problem is the key challenge for an extensive
      use of nuclear reactors as a major carbon free, sustainable, and applied highly
      reliable energy source. Partitioning and Transmutation (P&T) promises a solution
      for improved waste management. Current strategies rely on systems designed in the
      60's for the massive production of plutonium. We propose an innovative strategic
      development plan based on invention and innovation described with the concept of
      developments in s-curves identifying the current boundary conditions, and the
      evolvable objectives. This leads to the ultimate, universal vision for energy
      production characterized by minimal use of resources and production of waste,
      while being economically affordable and safe, secure and reliable in operation.
      This vision is transformed into a mission for a disruptive development of the
      future nuclear energy system operated by burning of existing spent nuclear fuel
      (SNF) without prior reprocessing. This highly innovative approach fulfils the
      sustainability goals and creates new options for P&T. A proof on the feasibility
      from neutronic point of view is given demonstrating sufficient breeding of
      fissile material from the inserted SNF. The system does neither require new
      resources nor produce additional waste, thus it provides a highly sustainable
      option for a future nuclear system fulfilling the requests of P&T as side effect.
      In addition, this nuclear system provides enhanced resistance against misuse of
      Pu and a significantly reduced fuel cycle. However, the new system requires a
      demand driven rethinking of the separation process to be efficient.

PMID- 28749953
TI  - Approaches to detect genetic effects that differ between two strata in genome
      wide meta-analyses: Recommendations based on a systematic evaluation.
AB  - Genome-wide association meta-analyses (GWAMAs) conducted separately by two strata
      have identified differences in genetic effects between strata, such as sex
      differences for body fat distribution. However, there are several approaches to
      identify such differences and an uncertainty which approach to use. Assuming the
      availability of stratified GWAMA results, we compare various approaches to
      identify between-strata differences in genetic effects. We evaluate type I error
      and power via simulations and analytical comparisons for different scenarios of
      strata designs and for different types of between-strata differences. For strata
      of equal size, we find that the genome-wide test for difference without any
      filtering is the best approach to detect stratum-specific genetic effects with
      opposite directions, while filtering for overall association followed by the
      difference test is best to identify effects that are predominant in one stratum.
      When there is no a priori hypothesis on the type of difference, a combination of
      both approaches can be recommended. Some approaches violate type I error control
      when conducted in the same data set. For strata of unequal size, the best
      approach depends on whether the genetic effect is predominant in the larger or in
      the smaller stratum. Based on real data from GIANT (>175 000 individuals), we
      exemplify the impact of the approaches on the detection of sex-differences for
      body fat distribution (identifying up to 10 loci). Our recommendations provide
      tangible guidelines for future GWAMAs that aim at identifying between-strata
      differences. A better understanding of such effects will help pinpoint the
      underlying mechanisms.

PMID- 28749954
TI  - Metabolic markers during pregnancy and their association with maternal and
      newborn weight status.
AB  - BACKGROUND/AIMS: Obesity during pregnancy increases the risk of adverse clinical
      outcomes and is associated with low-grade chronic inflammation. We describe
      maternal metabolic risk and inflammation by maternal weight status, and evaluate
      the association of metabolic and inflammatory markers with birthweight in a group
      of pregnant Mexican women. METHODS: This study derived from a prospective cohort
      of healthy pregnant women <14 weeks of gestation, receiving prenatal care at
      National Institute of Perinatology (Mexico, 2009-2013). Metabolic and
      inflammatory markers were measured in maternal serum in all three pregnancy
      trimesters (1st: 11.42+/-1.7; 2nd: 21.06+/-2.4; 3rd: 32.74+/-2.3 weeks).
      Pregestational weight was self-reported, and body mass index (BMI) was
      calculated. Gestational weight gain was evaluated in the third trimester.
      Newborn's weight was measured at birth. We carried out correlations, general
      mixed linear model and regression analyses, based on pregestational weight (self
      reported), body mass index (BMI), gestational weight gain (evaluated in the third
      trimester) and newborn weight (measured at birth). RESULTS: Of the 177 women
      included in the study (mean age = 26.93+/-8.49), thirty-eight percent (n = 67)
      were overweight or had obesity, and 32.8% (n = 58) showed excessive gestational
      weight gain. We found insulin, lipids (including total cholesterol, LDL
      cholesterol, HDL-cholesterol, and triglycerides-TG), leptin and interleukin 1b
      (IL-1b) all increased significantly (p<0.05) during pregnancy. Pregestational
      maternal weight status altered longitudinal concentrations of insulin, leptin,
      adiponectin, TG and C reactive protein. Excessive gestational weight gain was
      associated with higher maternal insulin in the third trimester (p<0.05). Early
      pregnancy leptin and TNFalpha were determinants of birthweight in women with
      normal weight, but not in overweight or obese women. CONCLUSIONS: Maternal weight
      status affected the concentrations of insulin, leptin, adiponectin, triglycerides
      and C reactive protein throughout pregnancy. The role of early leptin and
      TNFalpha in fetal growth need further study given the association was only
      observed in normal weight women. This study presents data distribution of
      metabolic and inflammatory markers of normal weight and overweight/obese women
      that did not develop GDM, preeclampsia nor macrosomia.

PMID- 28749955
TI  - Simultaneous detection of three pome fruit tree viruses by one-step multiplex
      quantitative RT-PCR.
AB  - A one-step multiplex real-time reverse transcription polymerase chain reaction
      (RT-qPCR) based on TaqMan probes was developed for the simultaneous detection of
      Apple mosaic virus (ApMV), Apple stem pitting virus (ASPV) and Apple stem
      grooving virus (ASGV) in total RNA of pome trees extracted with a CTAB method.
      The sensitivity of the method was established using in vitro synthesized viral
      transcripts serially diluted in RNA from healthy, virus-tested (negative) pome
      trees. The three viruses were simultaneously detected up to a 10-4 dilution of
      total RNA from a naturally triple-infected apple tree prepared in total RNA of
      healthy apple tissue. The newly developed RT-qPCR assay was at least one hundred
      times more sensitive than conventional single RT-PCRs. The assay was validated
      with 36 field samples for which nine triple and 11 double infections were
      detected. All viruses were detected simultaneously in composite samples at least
      up to the ratio of 1:150 triple-infected to healthy pear tissue, suggesting the
      assay has the capacity to examine rapidly a large number of samples in pome tree
      certification programs and surveys for virus presence.

PMID- 28749956
TI  - Functional characterization of sodium-pumping rhodopsins with different pumping
      properties.
AB  - Sodium pumping rhodopsins (NaRs) are a unique member of the microbial-type I
      rhodopsin family which actively transport Na+ and H+ depending on ionic
      condition. In this study, we surveyed 12 different NaRs from various sources of
      eubacteria for their electrophysiological as well as spectroscopic properties. In
      mammalian cells several of these NaRs exhibited a Na+ based pump photocurrent and
      four interesting candidates were chosen for further characterization. Voltage
      dependent photocurrent amplitudes revealed a membrane potential-sensitive
      turnover rate, indicating the presence of an electrically-charged intermediate(s)
      in the photocycle reaction. The NaR from Salinarimonas rosea DSM21201 exhibited a
      red-shifted absorption spectrum, and slower kinetics compared to the first
      described sodium pump, KR2. Although the ratio of Na+ to H+ ion transport varied
      among the NaRs we tested, the NaRs from Flagellimonas sp_DIK and Nonlabens
      sp_YIK_SED-11 showed significantly higher Na+ selectivity when compared to KR2.
      All four further investigated NaRs showed a functional expression in dissociated
      hippocampal neuron culture and hyperpolarizing activity upon light-stimulation.
      Additionally, all four NaRs allowed optical inhibition of electrically-evoked
      neuronal spiking. Although efficiency of silencing was 3-5 times lower than
      silencing with the enhanced version of the proton pump AR3 from Halorubrum
      sodomense, our data outlines a new approach for hyperpolarization of excitable
      cells without affecting the intracellular and extracellular proton environment.

PMID- 28749957
TI  - Delineation of the role of chromatin assembly and the Rtt101Mms1 E3 ubiquitin
      ligase in DNA damage checkpoint recovery in budding yeast.
AB  - The DNA damage checkpoint is activated in response to DNA double-strand breaks
      (DSBs). We had previously shown that chromatin assembly mediated by the histone
      chaperone Asf1 triggers inactivation of the DNA damage checkpoint in yeast after
      DSB repair, also called checkpoint recovery. Here we show that chromatin assembly
      factor 1 (CAF-1) also contributes to chromatin reassembly after DSB repair,
      explaining its role in checkpoint recovery. Towards understanding how chromatin
      assembly promotes checkpoint recovery, we find persistent presence of the damage
      sensors Ddc1 and Ddc2 after DSB repair in asf1 mutants. The genes encoding the E3
      ubiquitin ligase complex Rtt101Mms1 are epistatic to ASF1 for survival following
      induction of a DSB, and Rtt101Mms1 are required for checkpoint recovery after DSB
      repair but not for chromatin assembly. By contrast, the Mms22 substrate adaptor
      that is degraded by Rtt101Mms1 is required for DSB repair per se. Deletion of
      MMS22 blocks loading of Rad51 at the DSB, while deletion of ASF1 or RTT101 leads
      to persistent Rad51 loading. We propose that checkpoint recovery is promoted by
      Rtt101Mms1-mediated ubiquitylation of Mms22 in order to halt Mms22-dependent
      loading of Rad51 onto double-stranded DNA after DSB repair, in concert with the
      chromatin assembly-mediated displacement of Rad51 and checkpoint sensors from the
      site of repair.

PMID- 28749958
TI  - The impact of facial abnormalities and their spatial position on perception of
      cuteness and attractiveness of infant faces.
AB  - Research has demonstrated that how "cute" an infant is perceived to be has
      consequences for caregiving. Infants with facial abnormalities receive lower
      ratings of cuteness, but relatively little is known about how different
      abnormalities and their location affect these aesthetic judgements. The objective
      of the current study was to compare the impact of different abnormalities on the
      perception of infant faces, while controlling for infant identity. In two
      experiments, adult participants gave ratings of cuteness and attractiveness in
      response to face images that had been edited to introduce common facial
      abnormalities. Stimulus faces displayed either a haemangioma (a small, benign
      birth mark), strabismus (an abnormal alignment of the eyes) or a cleft lip (an
      abnormal opening in the upper lip). In Experiment 1, haemangioma had less of a
      detrimental effect on ratings than the more severe abnormalities. In Experiment
      2, we manipulated the position of a haemangioma on the face. We found small but
      robust effects of this position, with abnormalities in the top and on the left of
      the face receiving lower cuteness ratings. This is consistent with previous
      research showing that people attend more to the top of the face (particularly the
      eyes) and to the left hemifield.

PMID- 28749959
TI  - Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived
      lung cells increases COX-2 protein by altering mRNA stability.
AB  - Heightened inflammation, including expression of COX-2, is associated with
      chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon
      receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD
      derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette
      smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by
      mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced
      AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we
      investigated the expression of COX-2 as well as the expression of miR-146a, a
      miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from
      non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the
      involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and
      MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2
      protein was higher in COPD lung fibroblasts compared to Normal or Smoker
      fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung
      structural cells increased COX-2 protein by stabilizing the Cox-2 transcript.
      There was less induction of miR-146a in COPD-derived lung fibroblasts but this
      was not due to the AhR. Instead, we found that RelB, an NF-kappaB protein, was
      required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we
      conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism
      independent of miR-146a. Low levels of the AhR may therefore contribute to the
      heightened inflammation common in COPD patients.

PMID- 28749960
TI  - Effects of warming rate, acclimation temperature and ontogeny on the critical
      thermal maximum of temperate marine fish larvae.
AB  - Most of the thermal tolerance studies on fish have been performed on juveniles
      and adults, whereas limited information is available for larvae, a stage which
      may have a particularly narrow range in tolerable temperatures. Moreover,
      previous studies on thermal limits for marine and freshwater fish larvae (53
      studies reviewed here) applied a wide range of methodologies (e.g. the static or
      dynamic method, different exposure times), making it challenging to compare
      across taxa. We measured the Critical Thermal Maximum (CTmax) of Atlantic herring
      (Clupea harengus) and European seabass (Dicentrarchus labrax) larvae using the
      dynamic method (ramping assay) and assessed the effect of warming rate (0.5 to 9
      degrees C h-1) and acclimation temperature. The larvae of herring had a lower
      CTmax (lowest and highest values among 222 individual larvae, 13.1-27.0 degrees
      C) than seabass (lowest and highest values among 90 individual larvae, 24.2-34.3
      degrees C). At faster rates of warming, larval CTmax significantly increased in
      herring, whereas no effect was observed in seabass. Higher acclimation
      temperatures led to higher CTmax in herring larvae (2.7 +/- 0.9 degrees C
      increase) with increases more pronounced at lower warming rates. Pre-trials
      testing the effects of warming rate are recommended. Our results for these two
      temperate marine fishes suggest using a warming rate of 3-6 degrees C h-1: CTmax
      is highest in trials of relatively short duration, as has been suggested for
      larger fish. Additionally, time-dependent thermal tolerance was observed in
      herring larvae, where a difference of up to 8 degrees C was observed in the upper
      thermal limit between a 0.5- or 24-h exposure to temperatures >18 degrees C. The
      present study constitutes a first step towards a standard protocol for measuring
      thermal tolerance in larval fish.

PMID- 28749961
TI  - Prediction of novel target genes and pathways involved in irinotecan-resistant
      colorectal cancer.
AB  - BACKGROUND: Acquired drug resistance to the chemotherapeutic drug irinotecan (the
      active metabolite of which is SN-38) is one of the significant obstacles in the
      treatment of advanced colorectal cancer (CRC). The molecular mechanism or targets
      mediating irinotecan resistance are still unclear. It is urgent to find the
      irinotecan response biomarkers to improve CRC patients' therapy. METHODS: Genetic
      Omnibus Database GSE42387 which contained the gene expression profiles of
      parental and irinotecan-resistant HCT-116 cell lines was used. Differentially
      expressed genes (DEGs) between parental and irinotecan-resistant cells, protein
      protein interactions (PPIs), gene ontologies (GOs) and pathway analysis were
      performed to identify the overall biological changes. The most common DEGs in the
      PPIs, GOs and pathways were identified and were validated clinically by their
      ability to predict overall survival and disease free survival. The gene-gene
      expression correlation and gene-resistance correlation was also evaluated in CRC
      patients using The Cancer Genomic Atlas data (TCGA). RESULTS: The 135 DEGs were
      identified of which 36 were upregulated and 99 were down regulated. After mapping
      the PPI networks, the GOs and the pathways, nine genes (GNAS, PRKACB, MECOM,
      PLA2G4C, BMP6, BDNF, DLG4, FGF2 and FGF9) were found to be commonly enriched.
      Signal transduction was the most significant GO and MAPK pathway was the most
      significant pathway. The five genes (FGF2, FGF9, PRKACB, MECOM and PLA2G4C) in
      the MAPK pathway were all contained in the signal transduction and the levels of
      those genes were upregulated. The FGF2, FGF9 and MECOM expression were highly
      associated with CRC patients' survival rate but not PRKACB and PLA2G4C. In
      addition, FGF9 was also associated with irinotecan resistance and poor disease
      free survival. FGF2, FGF9 and PRKACB were positively correlated with each other
      while MECOM correlated positively with FGF9 and PLA2G4C, and correlated
      negatively with FGF2 and PRKACB after doing gene-gene expression correlation.
      CONCLUSION: Targeting the MAPK signal transduction pathway through the targeting
      of the FGF2, FGF9, MECOM, PLA2G4C and PRKACB might increase tumor responsiveness
      to irinotecan treatment.

PMID- 28749962
TI  - Severe imported malaria in children in France. A national retrospective study
      from 1996 to 2005.
AB  - BACKGROUNDS: Malaria is a leading cause of imported febrile illnesses in
      pediatric travelers, but few studies have addressed severe imported pediatric
      malaria. We aimed to determine the risk factors and the features of imported
      pediatric severe malaria. METHODS: We conducted a retrospective, descriptive
      study using the French National Reference Center for Imported Malaria database,
      in children aged 0-15 years who were hospitalized with a falciparum malaria from
      January 1st 1996 to December 31th 2005. Uncomplicated and severe cases of
      falciparum malaria were compared to identify risk factors for severe cases. In
      the hospitals that reported more than five severe cases during the study period,
      we evaluated severe cases for prognostic factors and assessed the accuracy WHO
      criteria for predicting severity. Given the rarity of deaths, adverse outcomes
      were defined as requiring major therapeutic procedures (MTPs)-e.g., sedation,
      mechanical ventilation, nasal oxygen therapy, blood transfusions, hemodialysis,
      fluid resuscitation-or pediatric intensive care unit (PICU) admission. RESULTS:
      Of 4150 pediatric malaria cases included in the study, 3299 were uncomplicated
      and 851 (20.5%) were severe. Only one death was recorded during this period.
      Predictors for severe falciparum malaria were: age <2 years (OR = 3.2, 95% CI =
      2.5-4.0, p <0.0001) and a travel in the Sahelian region (OR = 1.7, 95% CI = 1.3
      2.0, p = 0.0001). Of 422 severe malaria cases, a stay in a Sahelian region, lack
      of chemoprophylaxis, age <2 years or thrombocytopenia <100 x 10^3/mm^3 predicted
      adverse outcomes. Except for the hyperparasitemia threshold of 4%, the main WHO
      2000 criteria for severe malaria reliably predicted adverse outcomes. In our
      study, the threshold of parasitemia most predictive of a poor outcome was 8%.
      CONCLUSION: In imported pediatric malaria, children younger than 2 years deserve
      particular attention. The main WHO 2000 criteria for severity are accurate,
      except for the threshold of hyperparasitemia, which should be revised.

PMID- 28749963
TI  - Expression of intra- and extracellular granzymes in patients with typhoid fever.
AB  - BACKGROUND: Typhoid fever, caused by the intracellular pathogen Salmonella (S.)
      enterica serovar Typhi, remains a major cause of morbidity and mortality
      worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes
      mediated eradication of intracellular pathogens via the induction of cell death
      and which can also play a role in inflammation. We aimed to characterize the
      expression of extracellular and intracellular granzymes in patients with typhoid
      fever and whether the extracellular levels of granzyme correlated with IFN-gamma
      release. METHODS AND PRINCIPAL FINDINGS: We analyzed soluble protein levels of
      extracellular granzyme A and B in healthy volunteers and patients with confirmed
      S. Typhi infection on admission and day of discharge, and investigated whether
      this correlated with interferon (IFN)-gamma release, a cytokine significantly
      expressed in typhoid fever. The intracellular expression of granzyme A, B and K
      in subsets of lymphocytic cells was determined using flow cytometry. Patients
      demonstrated a marked increase of extracellular granzyme A and B in acute phase
      plasma and a correlation of both granzymes with IFN-gamma release. In patients,
      lower plasma levels of granzyme B, but not granzyme A, were found at day of
      discharge compared to admission, indicating an association of granzyme B with
      stage of disease. Peripheral blood mononuclear cells of typhoid fever patients
      had a higher percentage of lymphocytic cells expressing intracellular granzyme A
      and granzyme B, but not granzyme K, compared to controls. CONCLUSION: The marked
      increase observed in extra- and intracellular levels of granzyme expression in
      patients with typhoid fever, and the correlation with stage of disease, suggests
      a role for granzymes in the host response to this disease.

PMID- 28749964
TI  - Transmission risk of two chikungunya lineages by invasive mosquito vectors from
      Florida and the Dominican Republic.
AB  - Between 2014 and 2016 more than 3,800 imported human cases of chikungunya fever
      in Florida highlight the high risk for local transmission. To examine the
      potential for sustained local transmission of chikungunya virus (CHIKV) in
      Florida we tested whether local populations of Aedes aegypti and Aedes albopictus
      show differences in susceptibility to infection and transmission to two emergent
      lineages of CHIKV, Indian Ocean (IOC) and Asian genotypes (AC) in laboratory
      experiments. All examined populations of Ae. aegypti and Ae. albopictus
      mosquitoes displayed susceptibility to infection, rapid viral dissemination into
      the hemocoel, and transmission for both emergent lineages of CHIKV. Aedes
      albopictus had higher disseminated infection and transmission of IOC sooner after
      ingesting CHIKV infected blood than Ae. aegypti. Aedes aegypti had higher
      disseminated infection and transmission later during infection with AC than Ae.
      albopictus. Viral dissemination and transmission of AC declined during the
      extrinsic incubation period, suggesting that transmission risk declines with
      length of infection. Interestingly, the reduction in transmission of AC was less
      in Ae. aegypti than Ae. albopictus, suggesting that older Ae. aegypti females are
      relatively more competent vectors than similar aged Ae. albopictus females. Aedes
      aegypti originating from the Dominican Republic had viral dissemination and
      transmission rates for IOC and AC strains that were lower than for Florida
      vectors. We identified small-scale geographic variation in vector competence
      among Ae. aegypti and Ae. albopictus that may contribute to regional differences
      in risk of CHIKV transmission in Florida.

PMID- 28749965
TI  - Major bioactive phenolics in Bergenia species from the Indian Himalayan region:
      Method development, validation and quantitative estimation using UHPLC-QqQLIT
      MS/MS.
AB  - Bergenia species are important medicinal plants used in indigenous systems of
      medicine for their antilithiatic and diuretic properties. An ultra-high
      performance liquid chromatography coupled to hybrid linear ion trap triple
      quadrupole mass spectrometry (UHPLC-QqQLIT-MS/MS) method has been developed and
      validated for the estimation of quantitative variation of eight major bioactive
      phenolics in the rhizomes (150 samples) of four species of this herb, Bergenia
      (B. ciliata, B. ligulata, B. purpurascens and B. stracheyi). Chromatographic
      separation was obtained on a Waters ACQUITY UPLCTM BEH (ethylene bridged hybrid)
      C18 column with a mobile phase consisting of 0.1% (v/v) formic acid aqueous
      solution and acetonitrile under a gradient elution manner. A hybrid linear ion
      trap triple quadrupole mass spectrometer was operated in negative electrospray
      ionization mode with multiple reactions monitoring for detection and
      quantification of the eight compounds. The validated method demonstrated good
      linearity (r2 >= 0.9991), precision (RSD <= 1.87%) and accuracy (95.16-102.11%,
      RSD <= 1.83%) for all reference analytes. The quantitative results revealed that
      B. ligulata contains the highest amount of the major active marker-bergenin. The
      results also suggest that sensitive UHPLC-QqQLIT-MS/MS method, a sensitive,
      accurate and convenient one, could be helpful in identification of potential
      accession(s), rapid quality control and establishing authenticity of Bergenia
      species as raw material for pharmaceutical industries.

PMID- 28749966
TI  - Intrarater and interrater reliability of three classifications for scapular
      dyskinesis in athletes.
AB  - Clinical evaluation of scapular dyskinesis (SD) aims to identify abnormal
      scapulothoracic movement, underlying causal factors, and the potential
      relationship with shoulder symptoms. The literature proposes different methods of
      dynamic clinical evaluation of SD, but improved reliability and agreement values
      are needed. The present study aimed to evaluate the intrarater and interrater
      agreement and reliability of three SD classifications: 1) 4-type classification,
      2) Yes/No classification, and 3) scapular dyskinesis test (SDT). Seventy-five
      young athletes, including 45 men and 30 women, were evaluated. Raters evaluated
      the SD based on the three methods during one series of 8-10 cycles (at least
      eight and maximum of ten) of forward flexion and abduction with an external load
      under the observation of two raters trained to diagnose SD. The evaluation
      protocol was repeated after 3 h for intrarater analysis. The agreement percentage
      was calculated by dividing the observed agreement by the total number of
      observations. Reliability was calculated using Cohen Kappa coefficient, with a
      95% confidence interval (CI), defined by Kappa coefficient +/-1.96 multiplied by
      the measurement standard error. The interrater analyses showed an agreement
      percentage between 80% and 95.9% and an almost perfect reliability (k>0.81) for
      the three classification methods in all the test conditions, except the 4-type
      and SDT classification methods, which had substantial reliability (k<0.80) in
      shoulder abduction. Intrarater analyses showed agreement percentages between
      80.7% and 89.3% and substantial reliability (0.67 to 0.81) for both raters in the
      three classifications. CIs ranged from moderate to almost perfect categories.
      This indicates that the three SD classification methods investigated in this
      study showed high reliability values for both intrarater and interrater
      evaluation throughout a protocol that provided SD evaluation training of raters
      and included several repetitions of arm movements with external load during a
      live assessment.

PMID- 28749967
TI  - Predictors of nonfunctional arteriovenous access at hemodialysis initiation and
      timing of access creation: A registry-based study.
AB  - Determinants of nonfunctional arteriovenous (AV) access, including timing of AV
      access creation, have not been sufficiently described. We studied 29 945 patients
      who had predialysis AV access placement and were included in the French REIN
      registry from 2005 through 2013. AV access was considered nonfunctional when
      dialysis began with a catheter. We estimated crude and adjusted odds ratio (OR)
      with 95% confidence intervals (CI) of nonfunctional versus functional AV access
      associated with case-mix, facility characteristics, and timing of AV access
      creation. Analyses were stratified by dialysis start condition (planned or as an
      emergency) and comorbidity profile. Overall, 18% patients had nonfunctional AV
      access at hemodialysis initiation. In the group with planned dialysis start,
      female gender (OR 1.43, 95% CI 1.32-1.56), diabetes (OR 1.28, 95% CI 1.15-1.44),
      and a higher number of cardiovascular comorbidities (OR 1.27, 95% CI 1.09-1.49,
      and 1.31, 1.05-1.64, for 3 and >3 cardiovascular comorbidities versus none,
      respectively) were independent predictors of nonfunctional AV access. A higher
      percentage of AV access creation at the region level was associated with a lower
      rate of nonfunctional AV access (OR 0.98, 95% CI 0.98-0.99 per 1% increase). The
      odds of nonfunctional AV access decreased as time from creation to hemodialysis
      initiation increased up to 3 months in nondiabetic patients with fewer than 2
      cardiovascular comorbidities and 6 months in patients with diabetes or 2 or more
      such comorbidities. In conclusion, both patient characteristics and clinical
      practices may play a role in successful AV access use at hemodialysis initiation.
      Adjusting the timing of AV access creation to patients' comorbidity profiles may
      improve functional AV access rates.

PMID- 28749968
TI  - Analysis of age as a factor in NASA astronaut selection and career landmarks.
AB  - NASA's periodic selection of astronauts is a highly selective process accepting
      applications from the general population, wherein the mechanics of selection are
      not made public. This research was an effort to determine if biases (specifically
      age) exist in the process and, if so, at which points they might manifest. Two
      sets of analyses were conducted. The first utilized data requested via the
      Freedom of Information Act (FOIA) on NASA astronaut applicants for the 2009 and
      2013 selection years. Using a series of multinomial and logistic regressions, the
      data were analyzed to uncover whether age of the applicants linearly or
      nonlinearly affected their likelihood of receiving an invitation, as well as
      their likelihood of being selected into the astronaut program. The second used
      public data on age at selection and age at other career milestones for every
      astronaut selected from 1959 to 2013 to analyze trends in age over time using
      ordinary least-squares (OLS) regression and Pearson's correlation. The results
      for the FOIA data revealed a nonlinear relationship between age and receiving an
      interview, as well as age and selection into the astronaut program, but the most
      striking observation was the loss of age diversity at each stage of selection.
      Applicants younger or older than approximately 40 years were significantly less
      likely to receive invitations for interviews and were significantly less likely
      to be selected as an astronaut. Analysis of the public-source data for all
      selections since the beginning of the astronaut program revealed significant age
      trends over time including a gradual increase in selectee age and decreased
      tenure at NASA after last flight, with average age at retirement steady over the
      entire history of the astronaut program at approximately 48 years.

PMID- 28749969
TI  - TopologyNet: Topology based deep convolutional and multi-task neural networks for
      biomolecular property predictions.
AB  - : Although deep learning approaches have had tremendous success in image, video
      and audio processing, computer vision, and speech recognition, their applications
      to three-dimensional (3D) biomolecular structural data sets have been hindered by
      the geometric and biological complexity. To address this problem we introduce the
      element-specific persistent homology (ESPH) method. ESPH represents 3D complex
      geometry by one-dimensional (1D) topological invariants and retains important
      biological information via a multichannel image-like representation. This
      representation reveals hidden structure-function relationships in biomolecules.
      We further integrate ESPH and deep convolutional neural networks to construct a
      multichannel topological neural network (TopologyNet) for the predictions of
      protein-ligand binding affinities and protein stability changes upon mutation. To
      overcome the deep learning limitations from small and noisy training sets, we
      propose a multi-task multichannel topological convolutional neural network (MM
      TCNN). We demonstrate that TopologyNet outperforms the latest methods in the
      prediction of protein-ligand binding affinities, mutation induced globular
      protein folding free energy changes, and mutation induced membrane protein
      folding free energy changes. AVAILABILITY: weilab.math.msu.edu/TDL/.

PMID- 28749970
TI  - Effectiveness of physical activity on patients with depression and Parkinson's
      disease: A systematic review.
AB  - AIM: In this paper we aimed to systematically review the literature on physical
      activity's effect on depressive symptoms in Parkinson disease. BACKGROUND:
      Depression is a common symptom of Parkinson's disease and is associated with
      increased disability, rapid progression of motor symptoms, mortality, and adverse
      effects on Quality of Life. DESIGN: A systematic review of primary research was
      undertaken and conducted according to the Preferred Reporting Items for
      Systematic Reviews. DATA SOURCES: Databases Scopus, Psycho-info, CINAHL, PubMed,
      and ProQuest Cochrance were searched from January 2006 to June 2017. The language
      was restricted to English. REVIEW METHODS: Abstracts were screened and reviewed
      against the eligibility criteria (participants' mean age were >= 60 with PD, PA
      interventions, depression as one of outcome variables, and Randomized Control
      Trail or quasi-experimental design). Two reviewers appraised the quality of the
      data extracted. The modified Jadad scale assessed the quality of the methodology
      of the published papers. RESULTS: The database search yielded 769 abstracts, 11
      of which were included in this review and awarded scores ranging from 3 to 8
      (Scale scores range from 0 to 8 points, higher scores indicated better quality)
      by the raters. These 11 studies included 342 patients and executed 17 kinds of
      physical activity programs. Results of this review show empirical evidence to
      support the efficacy of physical activity for the population with Parkinson's
      disease. Aerobic training exercise significantly improved the participants'
      scores on the Unified Parkinson's Disease Rating Scale, the Beck Depression
      Inventory, and the Quality of Life of the patients. Qigong improved scores in
      UPDRS-III and decreased incidences of multiple non-motor symptoms and depression.
      Furthermore, a balance-training program, such as Tai Chi, can improve postural
      stability and Quality of Life. CONCLUSIONS: Physical activity may assuage the
      degeneration of motor skills and depression as well as increase the Quality of
      Life of Parkinson's disease patients, with aerobic training producing the best
      results. These findings suggest that physical activity, notably aerobic training,
      could be a good exercise strategy for patients with Parkinson's disease.

PMID- 28749971
TI  - Pediatric cancer risk in association with birth defects: A systematic review.
AB  - BACKGROUND: Many epidemiological studies have examined associations between birth
      defects (BDs) and pediatric malignancy over the past several decades. Our
      objective was to conduct a systematic literature review of studies reporting on
      this association. METHODS: We used librarian-designed searches of the PubMed
      Medline and Embase databases to identify primary research articles on pediatric
      neoplasms and BDs. English language articles from PubMed and Embase up to
      10/12/2015, and in PubMed up to 5/12/2017 following an updated search, were
      eligible for inclusion if they reported primary epidemiological research results
      on associations between BDs and pediatric malignancies. Two reviewers coded each
      article based on the title and abstract to identify eligible articles that were
      abstracted using a structured form. Additional articles were identified through
      reference lists and other sources. Results were synthesized for pediatric cancers
      overall and for nine major pediatric cancer subtypes. RESULTS: A total of 14,778
      article citations were identified, of which 80 met inclusion criteria. Pediatric
      cancer risk was increased in most studies in association with BDs overall with
      some notable specific findings, including increased risks for CNS tumors in
      association with CNS abnormalities and positive associations between rib
      anomalies and several pediatric cancer types. CONCLUSIONS: Some children born
      with BDs may be at increased risk for specific pediatric malignancy types. This
      work provides a foundation for future investigations that are needed to clarify
      specific BD types predisposing toward malignancy and possible underlying causes
      of both BDs and malignancy.

PMID- 28749972
TI  - Investigating asymmetric salt profiles for nanopore DNA sequencing with
      biological porin MspA.
AB  - Nanopore DNA sequencing is a promising single-molecule analysis technology. This
      technique relies on a DNA motor enzyme to control movement of DNA precisely
      through a nanopore. Specific experimental buffer conditions are required based on
      the preferred operating conditions of the DNA motor enzyme. While many DNA motor
      enzymes typically operate in salt concentrations under 100 mM, salt concentration
      simultaneously affects signal and noise magnitude as well as DNA capture rate in
      nanopore sequencing, limiting standard experimental conditions to salt
      concentrations greater than ~100 mM in order to maintain adequate resolution and
      experimental throughput. We evaluated the signal contribution from ions on both
      sides of the membrane (cis and trans) by varying cis and trans [KCl]
      independently during phi29 DNA Polymerase-controlled translocation of DNA through
      the biological porin MspA. Our studies reveal that during DNA translocation, the
      negatively charged DNA increases cation selectivity through MspA with the
      majority of current produced by the flow of K+ ions from trans to cis. Varying
      trans [K+] has dramatic effects on the signal magnitude, whereas changing cis [Cl
      ] produces only small effects. Good signal-to-noise can be maintained with cis
      [Cl-] as small as 20 mM, if the concentration of KCl on the trans side is kept
      high. These results demonstrate the potential of using salt-sensitive motor
      enzymes (helicases, polymerases, recombinases) in nanopore systems and offer a
      guide for selecting buffer conditions in future experiments to simultaneously
      optimize signal, throughput, and enzyme activity.

PMID- 28749973
TI  - Replication stress affects the fidelity of nucleosome-mediated epigenetic
      inheritance.
AB  - The fidelity of epigenetic inheritance or, the precision by which epigenetic
      information is passed along, is an essential parameter for measuring the
      effectiveness of the process. How the precision of the process is achieved or
      modulated, however, remains largely elusive. We have performed quantitative
      measurement of epigenetic fidelity, using position effect variegation (PEV) in
      Schizosaccharomyces pombe as readout, to explore whether replication perturbation
      affects nucleosome-mediated epigenetic inheritance. We show that replication
      stresses, due to either hydroxyurea treatment or various forms of genetic lesions
      of the replication machinery, reduce the inheritance accuracy of CENP-A/Cnp1
      nucleosome positioning within centromere. Mechanistically, we demonstrate that
      excessive formation of single-stranded DNA, a common molecular abnormality under
      these conditions, might have correlation with the reduction in fidelity of
      centromeric chromatin duplication. Furthermore, we show that replication stress
      broadly changes chromatin structure at various loci in the genome, such as
      telomere heterochromatin expanding and mating type locus heterochromatin
      spreading out of the boundaries. Interestingly, the levels of inheritable
      expanding at sub-telomeric heterochromatin regions are highly variable among
      independent cell populations. Finally, we show that HU treatment of the multi
      cellular organisms C. elegans and D. melanogaster affects epigenetically
      programmed development and PEV, illustrating the evolutionary conservation of the
      phenomenon. Replication stress, in addition to its demonstrated role in genetic
      instability, promotes variable epigenetic instability throughout the epigenome.

PMID- 28749974
TI  - Paroxysmal and unusual symptoms as first clinical manifestation of multiple
      sclerosis do not indicate benign prognosis-The PaSiMS II study.
AB  - BACKGROUND: Paroxysmal (PS) and unusual symptoms (US) account for approximately
      1.6% of initial manifestations of multiple sclerosis (MS) and have comparable
      conversion rates to clinically definite MS (CDMS) as classical bout onset
      symptoms (CS). However, long-term prognosis and clinical outcome of patients
      experiencing PS or US as first clinical manifestation are unclear. METHODS:
      Clinical, MRI and cerebrospinal fluid data were obtained retrospectively and
      patients presenting with PS or US were compared to patients with CS presentation.
      RESULTS: In a cohort of 532 relapsing onset MS patients followed for a mean
      period of 11.4 years (SD 3.6), 10 (1.9%) patients initially presented with PS/US.
      PS/US patients received disease modifying treatment (DMT) in a significantly
      smaller proportion immediately after the first clinical symptom (30% vs. 61.7%; p
      = 0.021) and during the observation period (60% vs. 83.5%; p = 0.033). In
      multivariate models correcting for sex, age at initial symptoms, complete
      remission of initial symptoms, total number of T2 and contrast-enhancing lesions,
      presence of oligoclonal bands and DMT exposure, PS/US were not associated with
      lower annualized relapse rate or lower EDSS over time. CONCLUSION: In addition to
      a similar conversion rate to CDMS, patients presenting with PS/US at disease
      onset display very similar relapse and disability rates as patients with CS
      onset. Consequently, initial presentation with PS/US does not indicate benign or
      atypical MS, but requires DMT initiation based on the same criteria as in CS
      patients.

PMID- 28749975
TI  - Circulating microRNAs and association with methacholine PC20 in the Childhood
      Asthma Management Program (CAMP) cohort.
AB  - INTRODUCTION: Circulating microRNAs (miRNA) are promising biomarkers for human
      diseases. Our study hypothesizes that circulating miRNA would reveal candidate
      biomarkers related to airway hyperresponsiveness (AHR) and provide biologic
      insights into asthma epigenetic influences. METHODS: Serum samples obtained at
      randomization for 160 children in the Childhood Asthma Management Program were
      profiled using a TaqMan miRNA array set. The association of the isolated miRNA
      with methacholine PC20 was assessed. Network and pathway analyses were performed.
      Functional validation of two significant miRNAs was performed in human airway
      smooth muscle cells (HASMs). RESULTS: Of 155 well-detected circulating miRNAs,
      eight were significantly associated with PC20 with the strongest association with
      miR-296-5p. Pathway analysis revealed miR-16-5p as a network hub, and involvement
      of multiple miRNAs interacting with genes in the FoxO and Hippo signaling
      pathways by KEGG analysis. Functional validation of two miRNA in HASM showed
      effects on cell growth and diameter. CONCLUSION: Reduced circulatory miRNA
      expression at baseline is associated with an increase in PC20. These miRNA
      provide biologic insights into, and may serve as biomarkers of, asthma severity.
      miR-16-5p and -30d-5p regulate airway smooth muscle phenotypes critically
      involved in asthma pathogenesis, supporting a mechanistic link to these findings.
      Functional ASM phenotypes may be directly relevant to AHR.

PMID- 28749976
TI  - Information filtering based on corrected redundancy-eliminating mass diffusion.
AB  - Methods used in information filtering and recommendation often rely on
      quantifying the similarity between objects or users. The used similarity metrics
      often suffer from similarity redundancies arising from correlations between
      objects' attributes. Based on an unweighted undirected object-user bipartite
      network, we propose a Corrected Redundancy-Eliminating similarity index (CRE)
      which is based on a spreading process on the network. Extensive experiments on
      three benchmark data sets-Movilens, Netflix and Amazon-show that when used in
      recommendation, the CRE yields significant improvements in terms of
      recommendation accuracy and diversity. A detailed analysis is presented to unveil
      the origins of the observed differences between the CRE and mainstream similarity
      indices.

PMID- 28749977
TI  - Preliminary research on the identification system for anthracnose and powdery
      mildew of sandalwood leaf based on image processing.
AB  - This paper presents a survey on a system that uses digital image processing
      techniques to identify anthracnose and powdery mildew diseases of sandalwood from
      digital images. Our main objective is researching the most suitable
      identification technology for the anthracnose and powdery mildew diseases of the
      sandalwood leaf, which provides algorithmic support for the real-time machine
      judgment of the health status and disease level of sandalwood. We conducted real
      time monitoring of Hainan sandalwood leaves with varying severity levels of
      anthracnose and powdery mildew beginning in March 2014. We used image
      segmentation, feature extraction and digital image classification and recognition
      technology to carry out a comparative experimental study for the image analysis
      of powdery mildew, anthracnose disease and healthy leaves in the field.
      Performing the actual test for a large number of diseased leaves pointed to three
      conclusions: (1) Distinguishing effects of BP (Back Propagation) neural network
      method, in all kinds of classical methods, for sandalwood leaf anthracnose and
      powdery mildew disease are relatively good; the size of the lesion areas were
      closest to the actual. (2) The differences between two diseases can be shown well
      by the shape feature, color feature and texture feature of the disease image. (3)
      Identifying and diagnosing the diseased leaves have ideal results by SVM, which
      is based on radial basis kernel function. The identification rate of the
      anthracnose and healthy leaves was 92% respectively, and that of powdery mildew
      was 84%. Disease identification technology lays the foundation for remote
      monitoring disease diagnosis, preparing for remote transmission of the disease
      images, which is a very good guide and reference for further research of the
      disease identification and diagnosis system in sandalwood and other species of
      trees.

PMID- 28749978
TI  - Occurrence of Penicillium verrucosum, ochratoxin A, ochratoxin B and citrinin in
      on-farm stored winter wheat from the Canadian Great Lakes Region.
AB  - The occurrence of P. verrucosum and ochratoxin A (OTA) were surveyed for 3 and 4
      years, respectively. A total of 250 samples was collected from an average of 30
      farms during the 2011, 2012, 2013 and 2014 winter seasons. Most storage bins
      surveyed were typically 11 m high round bins made of corrugated, galvanized
      steel, with flat-bottoms and conical roofs. Samples of clumped grain contained
      the most P. verrucosum (p<0.05, n = 10) followed by samples taken from the first
      load (n = 24, mean = 147+/-87 CFU/g) and last load (n = 17, mean = 101+/-77
      CFU/g). Five grain samples (2.2%) tested positive for OTA, citrinin and OTB at
      concentrations of 14.7+/-7.9, 4.9+/-1.9 and 1.2+/-0.7 ng/g, with only three
      samples exceeding 5 ng/g. Grain samples positive for OTA were related to moisture
      resulting from either condensation or migrating moist warm air in the bin or
      areas where precipitation including snow entered the bin. Bins containing grain
      and clumps contaminated with OTA were studied in detail. A number of
      statistically-significant risk factors for OTA contamination were identified.
      These included 1) grain clumps accumulated around or directly under manhole
      openings, 2) debris and residue of old grain or grain clumps collected from the
      bin walls or left on storage floor and augers and 3) grain clumps accumulated
      around side doors. Even when grain enters storage below the 14.5% threshold of
      moisture, condensation and moisture migration occurs in hotspots in modern
      corrugated steel storage bins. Hot spots of OTA contamination were most often in
      areas affected by moisture migration due to inadequate aeration and exposure to
      moisture from precipitation or condensation. Further, we found that the nature of
      the condensation affects the nature and distribution of small and isolated areas
      with high incidence of toxin contamination and/or P. verrucosum prevalence in the
      grain bins examined.

PMID- 28749979
TI  - Attitudes and decision-making about early-infant versus early-adolescent male
      circumcision: Demand-side insights for sustainable HIV prevention strategies in
      Zambia and Zimbabwe.
AB  - As countries approach their scale-up targets for the voluntary medical male
      circumcision program for HIV prevention, they are strategizing and planning for
      the sustainability phase to follow. Global guidance recommends circumcising
      adolescent (below 14 years) and/or early infant boys (aged 0-60 days), and
      countries need to consider several factors before prioritizing a cohort for their
      sustainability phase. We provide community and healthcare provider-side insights
      on attitudes and decision-making process as a key input for this strategic
      decision in Zambia and Zimbabwe. We studied expectant parents, parents of infant
      boys (aged 0-60 days), family members and neo-natal and ante-natal healthcare
      providers in Zambia and Zimbabwe. Our integrated methodology consisted of in
      depth qualitative and quantitative one-on-one interviews, and a simulated
      decision-making game, to uncover attitudes towards, and the decision-making
      process for, early adolescent or early infant medical circumcision (EAMC or
      EIMC). In both countries, parents viewed early infancy and early adolescence as
      equally ideal ages for circumcision (38% EIMC vs. 37% EAMC in Zambia; 24% vs. 27%
      in Zimbabwe). If offered for free, about half of Zambian parents and almost 2 in
      5 Zimbabwean parents indicated they would likely circumcise their infant boy;
      however, half of parents in each country perceived that the community would not
      accept EIMC. Nurses believed their facilities currently could not absorb EIMC
      services and that they would have limited ability to influence fathers, who were
      seen as having the primary decision-making authority. Our analysis suggests that
      EAMC is more accepted by the community than EIMC and is the path of least
      resistance for the sustainability phase of VMMC. However, parents or community
      members do not reject EIMC. Should countries choose to prioritize this cohort for
      their sustainability phase, a number of barriers around information, decision
      making by parents, and supply side will need to be addressed.

PMID- 28749980
TI  - Coverage and factors associated with influenza vaccination among kindergarten
      children 2-7 years old in a low-income city of north-western China (2014-2016).
AB  - Influenza vaccination has been shown to be the most effective preventive measure
      to reduce influenza virus infection and its related morbidity and mortality.
      Young children aged 6-59 months are recommended as one of the priority groups for
      seasonal influenza vaccination in China. Our study was conducted to evaluate the
      level of influenza vaccination coverage during 2014-15 and 2015-16 influenza
      seasons among kindergarten children aged 2-7 years in Xining, a low-income city
      of north-western China, and to explore potential factors for noncompliance
      associated with influenza vaccination. The coverage rate of influenza vaccination
      was 12.2% (95 CI: 10.6-14.2%) in 2014-15 and 12.8% (95 CI: 11.1-14.7%) in 2015
      16. The low coverage rate was found to be primarily associated with the lack of
      knowledge about influenza vaccine in children's parents. The most common reason
      for vaccine declination was the concern about adverse reactions of vaccine.
      Therefore tailored information should be provided by clinician and public health
      doctors for targeted groups through effective methods to improve public
      understanding of vaccination.

PMID- 28749981
TI  - A systematic review and meta-analysis on herpes zoster and the risk of cardiac
      and cerebrovascular events.
AB  - BACKGROUND: Patients who develop herpes zoster or herpes zoster ophthalmicus may
      be at risk for cerebrovascular and cardiac complications. We systematically
      reviewed the published literature to determine the association between herpes
      zoster and its subtypes with the occurrence of cerebrovascular and cardiac
      events. METHODS/RESULTS: Systematic searches of PubMed (MEDLINE), SCOPUS (Embase)
      and Google Scholar were performed in December 2016. Eligible studies were cohort,
      case-control, and self-controlled case-series examining the association between
      herpes zoster or subtypes of herpes zoster with the occurrence of cerebrovascular
      and cardiac events including stroke, transient ischemic attack, coronary heart
      disease, and myocardial infarction. Data on the occurrence of the examined events
      were abstracted. Odds ratios and their accompanying confidence intervals were
      estimated using random and fixed effects models with statistical heterogeneity
      estimated with the I2 statistic. Twelve studies examining 7.9 million patients up
      to 28 years after the onset of herpes zoster met our pre-defined eligibility
      criteria. Random and fixed effects meta-analyses showed that herpes zoster, type
      unspecified, and herpes zoster ophthalmicus were associated with a significantly
      increased risk of cerebrovascular events, without any evidence of statistical
      heterogeneity. Our meta-analysis also found a significantly increased risk of
      cardiac events associated with herpes zoster, type unspecified. CONCLUSIONS: Our
      results are consistent with the accumulating body of evidence that herpes zoster
      and herpes zoster ophthalmicus are significantly associated with cerebrovascular
      and cardiovascular events.

PMID- 28749982
TI  - Comparative genomics of the tardigrades Hypsibius dujardini and Ramazzottius
      varieornatus.
AB  - Tardigrada, a phylum of meiofaunal organisms, have been at the center of
      discussions of the evolution of Metazoa, the biology of survival in extreme
      environments, and the role of horizontal gene transfer in animal evolution.
      Tardigrada are placed as sisters to Arthropoda and Onychophora (velvet worms) in
      the superphylum Panarthropoda by morphological analyses, but many molecular
      phylogenies fail to recover this relationship. This tension between molecular and
      morphological understanding may be very revealing of the mode and patterns of
      evolution of major groups. Limnoterrestrial tardigrades display extreme
      cryptobiotic abilities, including anhydrobiosis and cryobiosis, as do bdelloid
      rotifers, nematodes, and other animals of the water film. These extremophile
      behaviors challenge understanding of normal, aqueous physiology: how does a
      multicellular organism avoid lethal cellular collapse in the absence of liquid
      water? Meiofaunal species have been reported to have elevated levels of
      horizontal gene transfer (HGT) events, but how important this is in evolution,
      and particularly in the evolution of extremophile physiology, is unclear. To
      address these questions, we resequenced and reassembled the genome of H.
      dujardini, a limnoterrestrial tardigrade that can undergo anhydrobiosis only
      after extensive pre-exposure to drying conditions, and compared it to the genome
      of R. varieornatus, a related species with tolerance to rapid desiccation. The 2
      species had contrasting gene expression responses to anhydrobiosis, with major
      transcriptional change in H. dujardini but limited regulation in R. varieornatus.
      We identified few horizontally transferred genes, but some of these were shown to
      be involved in entry into anhydrobiosis. Whole-genome molecular phylogenies
      supported a Tardigrada+Nematoda relationship over Tardigrada+Arthropoda, but rare
      genomic changes tended to support Tardigrada+Arthropoda.

PMID- 28749983
TI  - How does mandibular advancement with or without maxillary procedures affect
      pharyngeal airways? An overview of systematic reviews.
AB  - BACKGROUND: Mandibular advancement surgery may positively affect pharyngeal
      airways and therefore potentially beneficial to obstructive sleep apnea (OSA).
      OBJECTIVE: To collect evidence from published systematic reviews that have
      evaluated pharyngeal airway changes related to mandibular advancement with or
      without maxillary procedures. METHODOLOGY: PubMed, EMBASE, Web of Science, and
      Cochrane Library were searched without limiting language or timeline. Eligible
      systematic reviews evaluating changes in pharyngeal airway dimensions and
      respiratory parameters after mandibular advancement with or without maxillary
      surgery were identified and included. RESULTS: This overview has included eleven
      systematic reviews. Maxillomandibular advancement (MMA) increases linear, cross
      sectional plane and volumetric measurements of pharyngeal airways significantly
      (p<0.0001), while reducing the apnea-hypopnea index (AHI) and the respiratory
      disturbance index (RDI) significantly (p<0.0001). Two systematic reviews included
      primary studies that have evaluated single-jaw mandibular advancement, but did
      not discuss their effect onto pharyngeal airways. Based on the included primary
      studies of those systematic reviews, single-jaw mandibular advancement was
      reported to significantly increase pharyngeal airway dimensions (p<0.05);
      however, conclusive long-term results were lacking. CONCLUSION: MMA increases
      pharyngeal airway dimensions and is beneficial to patients suffering from OSA.
      However, more evidence is still needed to draw definite conclusion related to the
      effect of single-jaw mandibular advancement osteotomies on pharyngeal airways.

PMID- 28749984
TI  - Foregone benefits of important food crop improvements in Sub-Saharan Africa.
AB  - A number of new crops have been developed that address important traits of
      particular relevance for smallholder farmers in Africa. Scientists, policy
      makers, and other stakeholders have raised concerns that the approval process for
      these new crops causes delays that are often scientifically unjustified. This
      article develops a real option model for the optimal regulation of a risky
      technology that enhances economic welfare and reduces malnutrition. We consider
      gradual adoption of the technology and show that delaying approval reduces
      uncertainty about perceived risks of the technology. Optimal conditions for
      approval incorporate parameters of the stochastic processes governing the
      dynamics of risk. The model is applied to three cases of improved crops, which
      either are, or are expected to be, delayed by the regulatory process. The
      benefits and costs of the crops are presented in a partial equilibrium that
      considers changes in adoption over time and the foregone benefits caused by a
      delay in approval under irreversibility and uncertainty. We derive the
      equilibrium conditions where the net-benefits of the technology equal the costs
      that would justify a delay. The sooner information about the safety of the
      technology arrive, the lower the costs for justifying a delay need to be i.e. it
      pays more to delay. The costs of a delay can be substantial: e.g. a one year
      delay in approval of the pod-borer resistant cowpea in Nigeria will cost the
      country about 33 million USD to 46 million USD and between 100 and 3,000 lives.

PMID- 28749985
TI  - Fatigue in out-patients with inflammatory bowel disease: Prevalence and
      predictive factors.
AB  - BACKGROUND AND AIM: Fatigue is a common and bothersome symptom in inflammatory
      bowel disease (IBD) patients. The study was aimed to determine the relationship
      of biological and psychological factors with IBD-related fatigue. METHODS:
      Consecutive clinically inactive IBD outpatients receiving immunosuppressants or
      biological drugs were enrolled between January and December 2013. Patients
      completed a Fatigue score (FACIT-F), various psychological, quality of life (IBDQ
      9), and IBD activity scores. Biological parameters were assessed, including
      levels of interleukins (IL-5, IL-8 and IL-12) and micronutrients. RESULTS: We
      prospectively recruited 202 patients (28% ulcerative colitis and 72% Crohn's
      disease) for the study. Fatigue measured by FACIT-F score was prevalent in the
      studied population (54%, 96/177) and higher than in the general population. In
      the univariate analysis no relation was found between IL levels or micronutrient
      deficiencies and fatigue. Fatigue was significantly related to female sex,
      Crohn's disease, joint disorders, body mass index (BMI), psychological tests,
      thiopurine use, and anti-TNF treatment. All these variables were included in the
      multivariate analysis. Female sex (OR: 4.8), high BMI (OR:1.2) and higher
      depression rates (OR:1.2) were predictors of increased fatigue. High IBDQ-9 score
      (OR: 0.82) was significantly related to lower degrees of fatigue. CONCLUSION:
      Fatigue was prevalent in quiescent IBD patients with moderate-to-severe disease.
      It was associated with high levels of depression, low quality of life, and female
      sex. No association was found with the other biological and psychological factors
      evaluated.

PMID- 28749986
TI  - The role of the tissue factor and its inhibitor in the development of subclinical
      atherosclerosis in people living with HIV.
AB  - INTRODUCTION: HIV infection is associated with an increased risk of
      cardiovascular disease in connection with atherosclerosis and thromboembolic
      complications. The pathogenesis of atherosclerosis is still unclear in this group
      of patients. Studies on pathogenesis of atherosclerosis in the general population
      emphasize the role of the extrinsic pathway of blood coagulation, particularly
      the tissue factor (TF) and tissue factor pathway inhibitor (TFPI). The effect of
      persistent activation of the immune system on enhanced expression of TF on the
      surface of monocytes in subjects infected with HIV is known to be correlated with
      the level of HIV RNA in blood serum. STUDY AIM: The aim of this study was to
      evaluate the concentration of TF and its inhibitor TFPI in blood plasma, the
      impact of traditional and non-traditional cardiovascular risk factors on their
      concentration and the impact of both markers of haemostasis on the severity of
      subclinical atherosclerosis as assessed by the intima-media measurement of the
      carotid artery in HIV infected patients. MATERIALS: The study included 121 HIV
      infected people with known clinical, immunological and virological status. The
      control group consisted of 42 healthy individuals, selected in terms of age and
      sex. RESULTS AND CONCLUSIONS: Higher concentrations of TF occurred in HIV
      infected patients with a low current plasma HIV RNA level, nadir CD4+ T-cell
      count and longer duration of cumulative antiretroviral treatment. In multivariate
      analysis, it was the length of cumulative NRTI treatment that impacted on the
      concentration of TF. The determinants of cardiovascular disease (CVD) risk
      factors and inflammatory markers did not show any effect on the concentrations of
      TF. The TFPI level in HIV-infected patients was significantly higher than in the
      control group and was negatively correlated with the current level of HIV RNA and
      nadir CD4+ T-cell count, being higher in patients subjected to antiretroviral
      treatment. It was shown that the higher the cardiovascular risk and the higher
      the levels of total cholesterol, low-density lipoprotein cholesterol (LDL) and
      non-high-density lipoprotein cholesterol (non-HDL), the higher the concentrations
      of TFPI observed. The levels of TF and TFPI were positively correlated with
      carotid intima media thickness (cIMT); in the multivariate analysis, TF, non-HDL
      cholesterol and lifetime smoking (pack-years) independently affected the growth
      of cIMT. A similar effect on cIMT was demonstrated by TFPI.

PMID- 28749987
TI  - DUDE-Seq: Fast, flexible, and robust denoising for targeted amplicon sequencing.
AB  - We consider the correction of errors from nucleotide sequences produced by next
      generation targeted amplicon sequencing. The next-generation sequencing (NGS)
      platforms can provide a great deal of sequencing data thanks to their high
      throughput, but the associated error rates often tend to be high. Denoising in
      high-throughput sequencing has thus become a crucial process for boosting the
      reliability of downstream analyses. Our methodology, named DUDE-Seq, is derived
      from a general setting of reconstructing finite-valued source data corrupted by a
      discrete memoryless channel and effectively corrects substitution and homopolymer
      indel errors, the two major types of sequencing errors in most high-throughput
      targeted amplicon sequencing platforms. Our experimental studies with real and
      simulated datasets suggest that the proposed DUDE-Seq not only outperforms
      existing alternatives in terms of error-correction capability and time
      efficiency, but also boosts the reliability of downstream analyses. Further, the
      flexibility of DUDE-Seq enables its robust application to different sequencing
      platforms and analysis pipelines by simple updates of the noise model. DUDE-Seq
      is available at http://data.snu.ac.kr/pub/dude-seq.

PMID- 28749988
TI  - Switching of dominant retrotransposon silencing strategies from
      posttranscriptional to transcriptional mechanisms during male germ-cell
      development in mice.
AB  - Mammalian genomes harbor millions of retrotransposon copies, some of which are
      transpositionally active. In mouse prospermatogonia, PIWI-interacting small RNAs
      (piRNAs) combat retrotransposon activity to maintain the genomic integrity. The
      piRNA system destroys retrotransposon-derived RNAs and guides de novo DNA
      methylation at some retrotransposon promoters. However, it remains unclear
      whether DNA methylation contributes to retrotransposon silencing in
      prospermatogonia. We have performed comprehensive studies of DNA methylation and
      polyA(+) RNAs (transcriptome) in developing male germ cells from Pld6/Mitopld and
      Dnmt3l knockout mice, which are defective in piRNA biogenesis and de novo DNA
      methylation, respectively. The Dnmt3l mutation greatly reduced DNA methylation
      levels at most retrotransposons, but its impact on their RNA abundance was
      limited in prospermatogonia. In Pld6 mutant germ cells, although only a few
      retrotransposons exhibited reduced DNA methylation, many showed increased
      expression at the RNA level. More detailed analysis of RNA sequencing, nascent
      RNA quantification, profiling of cleaved RNA ends, and the results obtained from
      double knockout mice suggest that PLD6 works mainly at the posttranscriptional
      level. The increase in retrotransposon expression was larger in Pld6 mutants than
      it was in Dnmt3l mutants, suggesting that RNA degradation by the piRNA system
      plays a more important role than does DNA methylation in prospermatogonia.
      However, DNA methylation had a long-term effect: hypomethylation caused by the
      Pld6 or Dnmt3l mutation resulted in increased retrotransposon expression in
      meiotic spermatocytes. Thus, posttranscriptional silencing plays an important
      role in the early stage of germ cell development, then transcriptional silencing
      becomes important in later stages. In addition, intergenic and intronic
      retrotransposon sequences, in particular those containing the antisense L1
      promoters, drove ectopic expression of nearby genes in both mutant spermatocytes,
      suggesting that retrotransposon silencing is important for the maintenance of not
      only genomic integrity but also transcriptomic integrity.

PMID- 28749989
TI  - Respiratory events in ward are associated with later intensive care unit (ICU)
      admission and hospital mortality in onco-hematology patients not admitted to ICU
      after a first request.
AB  - INTRODUCTION: Prognostic impact of delayed intensive care unit(ICU) admission in
      critically ill cancer patients remains debatable. We determined predictive
      factors for later ICU admission and mortality in cancer patients initially not
      admitted after their first ICU request. METHODS: All cancer patients referred for
      an emergency ICU admission between 1 January 2012 and 31 August 2013 were
      included. RESULTS: Totally, 246(54.8%) patients were immediately admitted. Among
      203(45.2%) patients denied at the first request, 54(26.6%) were admitted later. A
      former ICU stay [OR: 2.75(1.12-6.75)], a request based on a clinical respiratory
      event[OR: 2.6(1.35-5.02)] and neutropenia[OR: 2.25(1.06-4.8)] were independently
      associated with later ICU admission. Survival of patients admitted immediately
      and later did not differ at ICU(78.5% and 70.4%, respectively; p = 0.2) or
      hospital(74% and 66%, respectively; p = 0.24) discharge. Hospital mortality of
      patients initially not admitted was 29.7% and independently associated with
      malignancy progression[OR: 3.15(1.6-6.19)], allogeneic hematopoietic stem cell
      transplantation[OR: 2.5(1.06-5.89)], a request based on a clinical respiratory
      event[OR: 2.36(1.22-4.56)] and severe sepsis[OR: 0.27(0.08-0.99)]. CONCLUSION:
      Compared with immediate ICU admission, later ICU admission was not associated
      with hospital mortality. Clinical respiratory events were independently
      associated with both later ICU admission and hospital mortality.

PMID- 28749990
TI  - Membrane filtration device for studying compression of fouling layers in membrane
      bioreactors.
AB  - A filtration devise was developed to assess compressibility of fouling layers in
      membrane bioreactors. The system consists of a flat sheet membrane with air
      scouring operated at constant transmembrane pressure to assess the influence of
      pressure on resistance of fouling layers. By fitting a mathematical model, three
      model parameters were obtained; a back transport parameter describing the
      kinetics of fouling layer formation, a specific fouling layer resistance, and a
      compressibility parameter. This stands out from other on-site filterability tests
      as model parameters to simulate filtration performance are obtained together with
      a characterization of compressibility. Tests on membrane bioreactor sludge showed
      high reproducibility. The methodology's ability to assess compressibility was
      tested by filtrations of sludges from membrane bioreactors and conventional
      activated sludge wastewater treatment plants from three different sites. These
      proved that membrane bioreactor sludge showed higher compressibility than
      conventional activated sludge. In addition, detailed information on the
      underlying mechanisms of the difference in fouling propensity were obtained, as
      conventional activated sludge showed slower fouling formation, lower specific
      resistance and lower compressibility of fouling layers, which is explained by a
      higher degree of flocculation.

PMID- 28749991
TI  - Nanofluidic digital PCR for the quantification of Norovirus for water quality
      assessment.
AB  - Sensitive detection of water- and foodborne enteric viruses is extremely
      relevant, especially due to the low concentrations in which they are found.
      Accurate and sensitive detection of Norovirus, the primary responsible for water-
      and foodborne outbreaks, is of particular importance. Quantification of Norovirus
      is commonly performed by quantitative RT-PCR (RT-qPCR). In recent years a new
      platform was developed, digital PCR, that quantifies without the need for a
      standard curve thus decreasing the errors associated with its utilization. The
      platform developed by LifeTechnologies, QuantStudio 3D Digital PCR is amongst the
      least studied digital platform and although it allows the direct detection of DNA
      targets it requires a two-step RT-PCR for the detection of RNA targets. In this
      work we developed a new protocol able to detect Norovirus using a one-step
      digital PCR reaction (RT-dPCR). The performance of the newly developed one-step
      digital PCR was compared to RT-qPCR for the detection of Norovirus genogroup I
      and genogroup II. The sensitivity of RT-dPCR was identical to that of RT-qPCR,
      and the quantitative data determined by both methods were not significantly
      different for most samples. This one-step absolute quantification approach is a
      useful tool to minimize the time spent currently using this particular platform
      to amplify viral RNA and to standardize quantification of enteric viruses in food
      and environmental samples. This study proved the usefulness of the newly
      developed RT-dPCR protocol for a sensitive and accurate detection of low-copy
      targets.

PMID- 28749992
TI  - The novel protein C9orf116 promotes rat liver cell line BRL-3A proliferation.
AB  - Our previous study has proved that the chromosome 9 open reading frame 116
      (C9orf116) (NM_001106564.1) was significantly up-regulated in the proliferation
      phase of liver regeneration. To study its possible physiological function, we
      analyzed the effect of C9orf116 on BRL-3A cells via over-expression and
      interference technique. MTT results showed that the cell viability of the
      interference group was significantly lower than the control group at 48h after
      transfection (P<0.05), whereas it was significantly higher in the over-expression
      group (P<0.05). The flow cytometry results showed that C9orf116 knockdown or over
      expression had little effect on BRL-3A cell apoptosis. However, the number of
      cells in division phase (G2/M) was significantly reduced in the interference
      group (P<0.05), but significantly increased in the over-expression group
      (P<0.01). Furthermore, the expressions of cell proliferation-related genes CCNA2,
      CCND1 and MYC both at mRNA and protein levels were down-regulated in the
      interference group and up-regulated in the over-expression group. Therefore, we
      concluded that C9orf116 may promote cell proliferation by modulating cell cycle
      transition and the expression of key genes CCNA2, CCND1 and MYC in BRL-3A cells.

PMID- 28749993
TI  - Functional characterization of an aquaporin from a microsporidium, Nosema
      bombycis.
AB  - Microsporidia are a diverse group of eukaryotic organisms, capable of causing
      parasitic infections in both vertebrates and invertebrates. During the
      germination process, there is an increase in the osmotic pressure of
      microsporidian spores. As part of this study, we cloned a homologous aquaporin
      gene in Nosema bombycis, and named it Nosema bombycis aquaporin (NbAQP). Sequence
      analysis revealed that the NbAQP contains an open reading frame with a length of
      750 bp and encodes a polypeptide of 249 amino acids. Amino acid sequence homology
      was greater than 50% that of five aquaporins from other microsporidian species.
      Indirect immunofluorescence (IFA) and immunogold electron microscopy showed NbAQP
      to be located predominantly in the spore wall of N. bombycis spores. The results
      of qRT-PCR analysis revealed that NbAQP expression remained high 0 h after
      inoculation and decreased sharply to 24 h, increased gradually from 2 days and
      peaked at 6 days. After expression of NbAQP in Xenopus laevis oocytes, it was
      observed that NbAQP can promote rapid penetration of water into oocytes. The
      associated permeation rate was 2-3 times that of the water-injected and
      uninjected oocytes. Antibody blocking experiments showed that the inhibition rate
      of spore germination was approximately 28% after antibody blocking. The
      difference in germination rate between the control group and the NbAQP group was
      significant (P < 0.05). This study shows for the first time that N. bombycis
      contains functional water channel proteins and provides a platform suitable for
      further research into the mechanisms underlying the regulation of NbAQP protein
      expression. Further study of NbAQP and their inhibitors may have significance for
      prevention of microsporidiosis.

PMID- 28749994
TI  - Ultrasonography versus magnetic resonance imaging in detecting and grading common
      extensor tendon tear in chronic lateral epicondylitis.
AB  - OBJECTIVES: To investigate the diagnostic performance and reliability of
      ultrasonography (US) in detecting and grading common extensor tendon (CET) tear
      in patients with chronic lateral epicondylitis (LE), using magnetic resonance
      imaging (MRI) as the reference standard. MATERIALS AND METHODS: The study
      comprised fifty-eight chronic LE patients. Each patient underwent US and MRI. CET
      status was classified as: high-grade tear (>=50% thickness), low-grade tear (<50%
      thickness), suspected tear (possible but not evident tear), no tear.
      Additionally, the following dichotomous scale was used: confirmed or unconfirmed
      CET tear. Relative US parameters (versus MRI) for detecting CET tear included:
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV) and accuracy. The agreement between US and MRI findings was measured
      using the weighted Cohen kappa coefficient (kappa). RESULTS: US showed moderate
      agreement with MRI in detecting and grading CET tear (kappa = 0.49). Sensitivity,
      specificity, and accuracy in CET tear detecting by US were 64.52%, 85.19%, and
      72.73%, respectively. PPV and NPV of US were 83.33% and 67.65%, respectively. No
      patient with unconfirmed CET tear on US had high-grade CET tear on MRI.
      CONCLUSION: Ultrasonography is a valuable imaging modality that can be used as a
      screening tool to exclude high-grade CET tear in chronic LE patients. Once a tear
      is evident on US, MRI should be considered to assess precisely the extent of
      tendon injury.

PMID- 28749995
TI  - Direction-of-arrival estimation of multipath signals using independent component
      analysis and compressive sensing.
AB  - Multipath signal is often considered an interference that must be removed. The
      coherence between multipath and direct component makes it difficult to use
      conventional direction-of-arrival (DOA) estimation methods in a smart antenna
      system. This study demonstrates a new multipath signal DOA estimation technique.
      Unlike the common methods, without decoherence preprocessing, the proposed
      algorithm first apply a complex fast independent component analysis (cFastICA)
      algorithm to obtain the steering vectors with multipath information that
      corresponds to each source signal. Then, according to the special structure of
      the obtained steering vectors and spatial sparsity of the multipath signal
      components, the algorithm uses the solution of the sparse signal reconstruction
      problem in the compressive sensing (CS) theory, and the DOA estimation of the
      multipath signal is translated into an l1 norm minimization problem. Finally, we
      search the space spectrums to acquire the DOAs for each direct component and
      multipath component. Comparative simulation tests and analysis prove the
      effectiveness of the proposed algorithm in estimation accuracy in underdetermined
      conditions.

PMID- 28749996
TI  - Misinformation lingers in memory: Failure of three pro-vaccination strategies.
AB  - People's inability to update their memories in light of corrective information
      may have important public health consequences, as in the case of vaccination
      choice. In the present study, we compare three potentially effective strategies
      in vaccine promotion: one contrasting myths vs. facts, one employing fact and
      icon boxes, and one showing images of non-vaccinated sick children. Beliefs in
      the autism/vaccines link and in vaccines side effects, along with intention to
      vaccinate a future child, were evaluated both immediately after the correction
      intervention and after a 7-day delay to reveal possible backfire effects. Results
      show that existing strategies to correct vaccine misinformation are ineffective
      and often backfire, resulting in the unintended opposite effect, reinforcing ill
      founded beliefs about vaccination and reducing intentions to vaccinate. The
      implications for research on vaccines misinformation and recommendations for
      progress are discussed.

PMID- 28749997
TI  - Difficulties and flaws in performing accurate determinations of zeta potentials
      of metal nanoparticles in complex solutions-Four case studies.
AB  - The zeta potential (ZP) is a parameter commonly used to characterize metal
      nanoparticles (NPs) in solution. Such determinations are for example performed in
      nanotoxicology since the ZP influences e.g. the interaction between cells and
      different biomolecules. Four case studies on different metal NPs (Cu and Zn NPs,
      and citrate capped Ag NPs) are presented in this study in order to provide
      guidance on how to accurately interpret and report ZP data. Solutions of high
      ionic strength (150 mM NaCl) induce a higher extent of particle agglomeration
      (elucidated with Ag NPs) when compared with conditions in 10 mM NaCl, which
      further complicates the prediction of the ZP due to e.g. sedimentation and
      broadening of the zeta potential distribution. The particle size is seldom
      included specifically in the standard ways of determining ZP (Huckel and
      Smoluchowski approximations). However corrections are possible when considering
      approximations of the Henry function. This was seen to improve the analysis of
      NPs, since there are cases when both the Huckel and the Smulochowski
      approximations are invalid. In biomolecule-containing cell media (BEGM), the
      signal from e.g. proteins may interfere with the measured ZP of the NPs. The
      intensity distribution of the ZP of both the blank solution and the solution
      containing NPs should hence be presented in addition to the mean value. Due to an
      increased ionic strength for dissolving of metal NPs (exemplified by Zn NPs), the
      released metal ions must be considered when interpreting the zeta potential
      measurements. In this work the effect was however negligible, as the particle
      size was several hundred nm, conditions that made the Smoluchowski approximation
      valid despite an increased ionic strength. However, at low ionic strengths (mM
      range) and small-sized NPs (tens of nm), the effect of released metal ions can
      influence the choice of model for determining the zeta potential. Sonication of
      particle dispersions influences not only the extent of metal release but also the
      outermost surface oxide composition, which often results in an increased ZP.
      Surface compositional changes were illustrated for sonicated and non-sonicated Cu
      NPs. In all, it can be concluded that accurate measurements and interpretations
      are possible in most cases by collecting and reporting complementary data on
      characteristics such as particle size, ZP distributions, blank sample
      information, and particle oxide composition.

PMID- 28749998
TI  - LC-MS/MS multiplex analysis of lysosphingolipids in plasma and amniotic fluid: A
      novel tool for the screening of sphingolipidoses and Niemann-Pick type C disease.
AB  - BACKGROUND: The biological diagnosis of sphingolipidoses currently relies on the
      measurement of specific enzymatic activities and/or genetic studies.
      Lysosphingolipids have recently emerged as potential biomarkers of
      sphingolipidoses and Niemann-Pick type C in plasma. METHODOLOGY: We developed a
      sensitive and specific method enabling the simultaneous quantification of
      lysosphingolipids by LC-MS/MS: lysoglobotriaosylceramide for Fabry disease,
      lysohexosylceramide (i.e. lysoglucosylceramide and/or lysogalactosylceramide) for
      Gaucher and Krabbe diseases, lysosphingomyelin and its carboxylated analogue
      lysosphingomyelin-509 for Niemann-Pick type A or B, and C diseases, lysoGM1
      ganglioside for GM1gangliosidosis and lysoGM2 ganglioside for GM2 gangliosidosis.
      FINDINGS: The diagnostic performances were validated in plasma samples analysing
      a large series of patients affected with sphingolipidoses and Niemann-Pick type C
      disease (n = 98), other inborn errors of metabolism (n = 23), and controls (n =
      228). The multiplex measurement of lysosphingolipids allowed the screening of
      Fabry (including female patients and late-onset variants), Gaucher and infantile
      Krabbe, Niemann-Pick type A/B and C diseases with high sensitivity and
      specificity. LysoGM1 and LysoGM2 were elevated in most of the patients affected
      with GM1 and GM2 gangliosidosis respectively. In amniotic fluid supernatant from
      pregnancies presenting non-immune hydrops fetalis (n = 77, including previously
      diagnosed Gaucher (n = 5), GM1 gangliosidosis (n = 4) and galactosialidosis (n =
      4) fetuses) and from normal pregnancies (n = 15), a specific and dramatic
      increase of lysohexosylceramide was observed only in the Gaucher amniotic fluid
      samples. INTERPRETATION: This multiplex assay which allows the simultaneous
      measurement of lysosphingolipids in plasma modifies the diagnostic strategy of
      sphingolipidoses and Niemann-Pick type C. Furthermore, in pregnancies presenting
      non-immune hydrops fetalis, lysohexosylceramide measurement in amniotic fluid
      offers a rapid screening of fetal Gaucher disease without waiting for
      glucocerebrosidase activity measurement in cultured amniocytes.

PMID- 28749999
TI  - Synthesis and biological evaluation of the progenitor of a new class of
      cephalosporin analogues, with a particular focus on structure-based computational
      analysis.
AB  - We present the synthesis and biological evaluation of the prototype of a new
      class of cephalosporins, containing an additional isolated beta lactam ring with
      two phenyl substituents. This new compound is effective against Gram positive
      microorganisms, with a potency similar to that of ceftriaxone, a cephalosporin
      widely used in clinics and taken as a reference, and with no cytotoxicity against
      two different human cell lines, even at a concentration much higher than the
      minimal inhibitory concentration tested. Additionally, a deep computational
      analysis has been conducted with the aim of understanding the contribution of its
      moieties to the binding energy towards several penicillin-binding proteins from
      both Gram positive and Gram negative bacteria. All these results will help us
      developing derivatives of this compound with improved chemical and biological
      properties, such as a broader spectrum of action and/or an increased affinity
      towards their molecular targets.

PMID- 28750000
TI  - Comparison of hemolytic activity of the intermediate subunit of Entamoeba
      histolytica and Entamoeba dispar lectins.
AB  - Galactose and N-acetyl-D-galactosamine-inhibitable lectin of Entamoeba
      histolytica has roles in pathogenicity and induction of protective immunity in
      rodent models of amoebiasis. Recently, the intermediate subunit of the lectin,
      Igl1, of E. histolytica has been shown to have hemolytic activity. However, the
      corresponding lectin is also expressed in a non-virulent species, Entamoeba
      dispar, and another subunit, Igl2, is expressed in the protozoa. Therefore, in
      this study, we compared the activities of Igl1 and Igl2 subunits from E.
      histolytica and E. dispar using various regions of recombinant Igl proteins
      expressed in Escherichia coli. The recombinant E. dispar Igl proteins had
      comparable hemolytic activities with those of E. histolytica Igl proteins.
      Furthermore, Igl1 gene-silenced E. histolytica trophozoites showed less hemolytic
      activity compared with vector-transfected trophozoites, indicating that the
      expression level of Igl1 protein influences the activity. These results suggest
      that the lower hemolytic activity in E. dispar compared with E. histolytica
      reflects the lower expression level of Igl1 in the E. dispar parasite.

PMID- 28750001
TI  - Classical conditioning without verbal suggestions elicits placebo analgesia and
      nocebo hyperalgesia.
AB  - The aim of this study was to examine the relationships among classical
      conditioning, expectancy, and fear in placebo analgesia and nocebo hyperalgesia.
      A total of 42 healthy volunteers were randomly assigned to three groups: placebo,
      nocebo, and control. They received 96 electrical stimuli, preceded by either
      orange or blue lights. A hidden conditioning procedure, in which participants
      were not informed about the meaning of coloured lights, was performed in the
      placebo and nocebo groups. Light of one colour was paired with pain stimuli of
      moderate intensity (control stimuli), and light of the other colour was paired
      with either nonpainful stimuli (in the placebo group) or painful stimuli of high
      intensity (in the nocebo group). In the control group, both colour lights were
      followed by control stimuli of moderate intensity without any conditioning
      procedure. Participants rated pain intensity, expectancy of pain intensity, and
      fear. In the testing phase, when both of the coloured lights were followed by
      identical moderate pain stimuli, we found a significant analgesic effect in the
      placebo group, and a significant hyperalgesic effect in the nocebo group. Neither
      expectancy nor fear ratings predicted placebo analgesia or nocebo hyperalgesia.
      It appears that a hidden conditioning procedure, without any explicit verbal
      suggestions, elicits placebo and nocebo effects, however we found no evidence
      that these effects are predicted by either expectancy or fear. These results
      suggest that classical conditioning may be a distinct mechanism for placebo and
      nocebo effects.

PMID- 28750002
TI  - DNA-PKcs controls calcineurin mediated IL-2 production in T lymphocytes.
AB  - Loss of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity in
      mammals results in severe combined immuno-deficiency (SCID). This SCID phenotype
      has been postulated to be due solely to the function of DNA-PKcs in V(D)J
      recombination, a process critical for lymphocyte maturation. However; we show
      that DNA-PKcs is required for IL-2 production via regulation of the calcineurin
      signaling pathway. Reducing DNA-PKcs activity in activated T cells either by
      shRNA or an inhibitor significantly reduced IL-2 production by blocking
      calcineurin activity and the translocation of NFAT into the nucleus.
      Additionally, we show that DNA-PKcs exerts its effect on calcineurin by altering
      the expression of the endogenous calcineurin inhibitor Cabin1 through activation
      of the kinase CHK2, a known Cabin1 regulator. The discovery of DNA-PKcs as a
      potent regulator of IL-2 production will drive continued investigation of small
      molecule inhibition of this enzyme within the clinic.

PMID- 28750003
TI  - Chrysodeixis chalcites nucleopolyhedrovirus (ChchNPV): Natural occurrence and
      efficacy as a biological insecticide on young banana plants in greenhouse and
      open-field conditions on the Canary Islands.
AB  - Chrysodeixis chalcites, an important pest of banana crops on the Canary Islands,
      is usually controlled by chemical insecticides. The present study aimed to
      evaluate the efficacy of the most prevalent isolate of the Chrysodeixis chalcites
      nucleopolyhedrovirus (ChchNPV, Baculoviridae) as a biological insecticide.
      Overall the prevalence of ChchNPV infection in C. chalcites populations was 2.3%
      (103 infected larvae out of 4,438 sampled), but varied from 0-4.8% on Tenerife
      and was usually low (0-2%) on the other islands. On Tenerife, infected larvae
      were present at 11 out of 17 plantations sampled. The prevalence of infection in
      larvae on bananas grown under greenhouse structures was significantly higher (3%)
      than in open-field sites (1.4%). The ChchNPV-TF1 isolate was the most abundant
      and widespread of four genetic variants of the virus. Application of 1.0x109
      viral occlusion bodies (OBs)/l of ChchNPV-TF1 significantly reduced C. chalcites
      foliar damage in young banana plants as did commonly used pesticides, both in
      greenhouse and open-field sites. The insecticidal efficacy of ChchNPV-TF1 was
      similar to that of indoxacarb and a Bacillus thuringiensis (Bt)-based insecticide
      in one year of trials and similar to Bt in the following year of trails in
      greenhouse and field crops. However, larvae collected at different time intervals
      following virus treatments and reared in the laboratory experienced 2-7 fold more
      mortality than insects from conventional insecticide treatments. This suggests
      that the acquisition of lethal dose occurred over an extended period (up to 7
      days) compared to a brief peak in larvae on plants treated with conventional
      insecticides. These results should prove useful for the registration of a ChchNPV
      based insecticide for integrated management of this pest in banana crops on the
      Canary Islands.

PMID- 28750004
TI  - Vertical transmission of human African trypanosomiasis: Clinical evolution and
      brain MRI of a mother and her son.

PMID- 28750005
TI  - From grid cells to place cells with realistic field sizes.
AB  - While grid cells in the medial entorhinal cortex (MEC) of rodents have multiple,
      regularly arranged firing fields, place cells in the cornu ammonis (CA) regions
      of the hippocampus mostly have single spatial firing fields. Since there are
      extensive projections from MEC to the CA regions, many models have suggested that
      a feedforward network can transform grid cell firing into robust place cell
      firing. However, these models generate place fields that are consistently too
      small compared to those recorded in experiments. Here, we argue that it is
      implausible that grid cell activity alone can be transformed into place cells
      with robust place fields of realistic size in a feedforward network. We propose
      two solutions to this problem. Firstly, weakly spatially modulated cells, which
      are abundant throughout EC, provide input to downstream place cells along with
      grid cells. This simple model reproduces many place cell characteristics as well
      as results from lesion studies. Secondly, the recurrent connections between place
      cells in the CA3 network generate robust and realistic place fields. Both
      mechanisms could work in parallel in the hippocampal formation and this
      redundancy might account for the robustness of place cell responses to a range of
      disruptions of the hippocampal circuitry.

PMID- 28750006
TI  - The impact of repetitive long-duration water immersion on vascular function.
AB  - While physiological responses to water immersion (WI) are well-studied, the
      vascular responses after WI are less understood. Fifteen male subjects performed
      six-hour resting thermoneutral water immersions (WI) at 1.35 atmospheres absolute
      for four consecutive days, with follow-up on the fifth day. Measurements included
      peripheral endothelial function and augmentation index (PAT, peripheral arterial
      tonometry), beat-to-beat blood pressure (BP, photoplethysmography), heart rate
      (HR), and plasma volume (PV) calculated from changes in hemoglobin and
      hematocrit. The reactive hyperemia index (RHI), a marker of peripheral
      endothelial function, increased with repeated immersions (p = 0.008). By WI2 and
      WI3, RHI increased 12% and 16%, respectively, compared to WI1 values, but no
      significant differences were detected between WI4 and WI1 for either measure.
      Absolute augmentation index (AI) increased by an average of 33% (p<0.001) and AI
      normalized for HR (AI@75) by 11% (p = 0.12) following each WI. PV decreased
      significantly by 13.2% following WI and remained 6.8% lower at follow-up compared
      to pre-WI. Systolic blood pressure significantly decreased by an average of 2.5%
      following each WI (p = 0.012). Compared to pre-WI HR, average post-WI HR
      decreased 4.3% lower (p<0.001), but increased overall by 8.2% over the course of
      repeated WI (p<0.001). Total peripheral resistance increased by an average of
      13.1% following WI (p = 0.003). Thus, peripheral endothelial function increases
      after two days of WI, and PAT-derived measures of arterial stiffness increase
      transiently post-WI. Additionally, BP and PAT-derived endothelial function
      diverge from their usual associations with arterial stiffness (i.e. augmentation
      index) in the context of WI.

PMID- 28750007
TI  - Adding tsetse control to medical activities contributes to decreasing
      transmission of sleeping sickness in the Mandoul focus (Chad).
AB  - BACKGROUND: Gambian sleeping sickness or HAT (human African trypanosomiasis) is a
      neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by
      riverine species of tsetse. A global programme aims to eliminate the disease as a
      public health problem by 2020 and stop transmission by 2030. In the South of
      Chad, the Mandoul area is a persistent focus of Gambian sleeping sickness where
      around 100 HAT cases were still diagnosed and treated annually until 2013. Pre
      2014, control of HAT relied solely on case detection and treatment, which lead to
      a gradual decrease in the number of cases of HAT due to annual screening of the
      population. METHODS: Because of the persistence of transmission and detection of
      new cases, we assessed whether the addition of vector control to case detection
      and treatment could further reduce transmission and consequently, reduce annual
      incidence of HAT in Mandoul. In particular, we investigated the impact of
      deploying 'tiny targets' which attract and kill tsetse. Before tsetse control
      commenced, a census of the human population was conducted and their settlements
      mapped. A pre-intervention survey of tsetse distribution and abundance was
      implemented in November 2013 and 2600 targets were deployed in the riverine
      habitats of tsetse in early 2014, 2015 and 2016. Impact on tsetse and on the
      incidence of sleeping sickness was assessed through nine tsetse monitoring
      surveys and four medical surveys of the human population in 2014 and 2015.
      Mathematical modelling was used to assess the relative impact of tsetse control
      on incidence compared to active and passive screening. FINDINGS: The census
      indicated that a population of 38674 inhabitants lived in the vicinity of the
      Mandoul focus. Within this focus in November 2013, the vector is Glossina
      fuscipes fuscipes and the mean catch of tsetse from traps was 0.7 flies/trap/day
      (range, 0-26). The catch of tsetse from 44 sentinel biconical traps declined
      after target deployment with only five tsetse being caught in nine surveys giving
      a mean catch of 0.005 tsetse/trap/day. Modelling indicates that 70.4% (95% CI: 51
      95%) of the reduction in reported cases between 2013 and 2015 can be attributed
      to vector control with the rest due to medical intervention. Similarly tiny
      targets are estimated to have reduced new infections dramatically with 62.8% (95%
      CI: 59-66%) of the reduction due to tsetse control, and 8.5% (95% 8-9%) to
      enhanced passive detection. Model predictions anticipate that elimination as a
      public health problem could be achieved by 2018 in this focus if vector control
      and screening continue at the present level and, furthermore, there may have been
      virtually no transmission since 2015. CONCLUSION: This work shows that tiny
      targets reduced the numbers of tsetse in this focus in Chad, which may have
      interrupted transmission and the combination of tsetse control to medical
      detection and treatment has played a major role in reducing in HAT incidence in
      2014 and 2015.

PMID- 28750008
TI  - Physiological responses of coccolithophores to abrupt exposure of naturally low
      pH deep seawater.
AB  - Upwelling is the process by which deep, cold, relatively high-CO2, nutrient-rich
      seawater rises to the sunlit surface of the ocean. This seasonal process has
      fueled geoengineering initiatives to fertilize the surface ocean with deep
      seawater to enhance productivity and thus promote the drawdown of CO2.
      Coccolithophores, which inhabit many upwelling regions naturally 'fertilized' by
      deep seawater, have been investigated in the laboratory in the context of ocean
      acidification to determine the extent to which nutrients and CO2 impact their
      physiology, but few data exist in the field except from mesocosms. Here, we used
      the Porcupine Abyssal Plain (north Atlantic Ocean) Observatory to retrieve
      seawater from depths with elevated CO2 and nutrients, mimicking geoengineering
      approaches. We tested the effects of abrupt natural deep seawater fertilization
      on the physiology and biogeochemistry of two strains of Emiliania huxleyi of
      known physiology. None of the strains tested underwent cell divisions when
      incubated in waters obtained from <1,000 m (pH = 7.99-8.08; CO2 = 373-485 p.p.m;
      1.5-12 MUM nitrate). However, growth was promoted in both strains when cells were
      incubated in seawater from ~1,000 m (pH = 7.9; CO2 ~560 p.p.m.; 14-17 MUM
      nitrate) and ~4,800 m (pH = 7.9; CO2 ~600 p.p.m.; 21 MUM nitrate). Emiliania
      huxleyi strain CCMP 88E showed no differences in growth rate or in cellular
      content or production rates of particulate organic (POC) and inorganic (PIC)
      carbon and cellular particulate organic nitrogen (PON) between treatments using
      water from 1,000 m and 4,800 m. However, despite the N:P ratio of seawater being
      comparable in water from ~1,000 and ~4,800 m, the PON production rates were three
      times lower in one incubation using water from ~1,000 m compared to values
      observed in water from ~4,800 m. Thus, the POC:PON ratios were threefold higher
      in cells that were incubated in ~1,000 m seawater. The heavily calcified strain
      NZEH exhibited lower growth rates and PIC production rates when incubated in
      water from ~4,800 m compared to ~1,000 m, while cellular PIC, POC and PON were
      higher in water from 4,800 m. Calcite Sr/Ca ratios increased with depth despite
      constant seawater Sr/Ca, indicating that upwelling changes coccolith
      geochemistry. Our study provides the first experimental and field trial of a
      geoengineering approach to test how deep seawater impacts coccolithophore
      physiological and biogeochemical properties. Given that coccolithophore growth
      was only stimulated using waters obtained from >1,000 m, artificial upwelling
      using shallower waters may not be a suitable approach for promoting carbon
      sequestration for some locations and assemblages, and should therefore be
      investigated on a site-by-site basis.

PMID- 28750009
TI  - mRNA/protein sequence complementarity and its determinants: The impact of
      affinity scales.
AB  - It has recently been demonstrated that the nucleobase-density profiles of mRNA
      coding sequences are related in a complementary manner to the nucleobase-affinity
      profiles of their cognate protein sequences. Based on this, it has been proposed
      that cognate mRNA/protein pairs may bind in a co-aligned manner, especially if
      unstructured. Here, we study the dependence of mRNA/protein sequence
      complementarity on the properties of the nucleobase/amino-acid affinity scales
      used. Specifically, we sample the space of randomly generated scales by employing
      a Monte Carlo strategy with a fitness function that depends directly on the level
      of complementarity. For model organisms representing all three domains of life,
      we show that even short searches reproducibly converge upon highly optimized
      scales, implying that the topology of the underlying fitness landscape is
      decidedly funnel-like. Furthermore, the optimized scales, generated without any
      consideration of the physicochemical attributes of nucleobases or amino acids,
      resemble closely the nucleobase/amino-acid binding affinity scales obtained from
      experimental structures of RNA-protein complexes. This provides support for the
      claim that mRNA/protein sequence complementarity may indeed be related to binding
      between the two. Finally, we characterize suboptimal scales and show that
      intermediate-to-high complementarity can be reached by substantially diverse
      scales, but with select amino acids contributing disproportionally. Our results
      expose the dependence of cognate mRNA/protein sequence complementarity on the
      properties of the underlying nucleobase/amino-acid affinity scales and provide
      quantitative constraints that any physical scales need to satisfy for the
      complementarity to hold.

PMID- 28750010
TI  - Intensive care discharge delay is associated with increased hospital length of
      stay: A multicentre prospective observational study.
AB  - BACKGROUND: Some patients experience a delayed discharge from the intensive care
      unit (ICU) where the intended and actual discharge times do not coincide. The
      clinical implications of this remain unclear. OBJECTIVE: To determine the
      incidence and duration of delayed ICU discharge, identify the reasons for delay
      and evaluate the clinical consequences. METHODS: Prospective multi-centre
      observational study involving five ICUs over a 3-month period. Delay in discharge
      was defined as >6 hours from the planned discharge time. The primary outcome
      measure was hospital length stay after ICU discharge decision. Secondary outcome
      measures included ICU discharge after-hours, incidence of delirium, survival to
      hospital discharge, discharge destination, the incidence of ICU acquired
      infections, revocation of ICU discharge decision, unplanned readmissions to ICU
      within 72 hours, review of patients admitting team after ICU discharge decision.
      RESULTS: A total of 955 out of 1118 patients discharged were included in
      analysis. 49.9% of the patients discharge was delayed. The most common reason
      (74%) for delay in discharge was non-availability of ward bed. The median
      duration of the delay was 24 hours. On univariable analysis, the duration of
      hospital stay from the time of ICU discharge decision was significantly higher in
      patients who had ICU discharge delay (Median days-5 vs 6; p = 0.003). After-hours
      discharge was higher in patients whose discharge was delayed (34% Vs 10%;
      p<0.001). There was no statistically significant difference in the other
      secondary outcomes analysed. Multivariable analysis adjusting for known
      confounders revealed delayed ICU discharge was independently associated with
      increased hospital length of stay. CONCLUSION: Half of all ICU patients
      experienced a delay in ICU discharge. Delayed discharge was associated with
      increased hospital length of stay.

PMID- 28750011
TI  - Leptospira interrogans causes quantitative and morphological disturbances in
      adherens junctions and other biological groups of proteins in human endothelial
      cells.
AB  - Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life
      threatening infection called leptospirosis. This infection is reported worldwide
      with higher risk in tropical regions. Symptoms of leptospirosis range from mild
      illness to severe illness such as liver damage, kidney failure, respiratory
      distress, meningitis, and fatal hemorrhagic disease. Invasive species of
      Leptospira rapidly disseminate to multiple tissues where this bacterium damages
      host endothelial cells, increasing vascular permeability. Despite the burden in
      humans and animals, the pathogenic mechanisms of Leptospira infection remain to
      be elucidated. The pathogenic leptospires adhere to endothelial cells and
      permeabilize endothelial barriers in vivo and in vitro. In this study, human
      endothelial cells were infected with the pathogenic L. interrogans serovar
      Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate
      morphological changes and other distinctive phenotypes of host cell proteins by
      fluorescence microscopy. Among those analyzed, 17 proteins from five biological
      classes demonstrated distinctive phenotypes in morphology and/or signal intensity
      upon infection with Leptospira. The affected biological groups include: 1)
      extracellular matrix, 2) intercellular adhesion molecules and cell surface
      receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a
      cytoskeletal protein. Infection with the pathogenic strain most profoundly
      disturbed the biological structures of adherens junctions (VE-cadherin and
      catenins) and actin filaments. Our data illuminate morphological disruptions and
      reduced signals of cell-cell junction proteins and filamentous actin in L.
      interrogans-infected endothelial cells. In addition, Leptospira infection,
      regardless of pathogenic status, influenced other host proteins belonging to
      multiple biological classes. Our data suggest that this zoonotic agent may damage
      endothelial cells via multiple cascades or pathways including endothelial barrier
      damage and inflammation, potentially leading to vascular hyperpermeability and
      severe illness in vivo. This work provides new insights into the
      pathophysiological mechanisms of Leptospira infection.

PMID- 28750012
TI  - Increased level and interferon-gamma production of circulating natural killer
      cells in patients with scrub typhus.
AB  - BACKGROUND: Natural killer (NK) cells are essential immune cells against several
      pathogens. Not much is known regarding the roll of NK cells in Orientia
      tsutsugamushi infection. Thus, this study aims to determine the level, function,
      and clinical relevance of NK cells in patients with scrub typhus.
      METHODOLOGY/PRINCIPAL FINDINGS: This study enrolled fifty-six scrub typhus
      patients and 56 health controls (HCs). The patients were divided into subgroups
      according to their disease severity. A flow cytometry measured NK cell level and
      function in peripheral blood. Circulating NK cell levels and CD69 expressions
      were significantly increased in scrub typhus patients. Increased NK cell levels
      reflected disease severity. In scrub typhus patients, tests showed their NK cells
      produced higher amounts of interferon (IFN)-gamma after stimulation with
      interleukin (IL)-12 and IL-18 relative to those of HCs. Meanwhile, between scrub
      typhus patients and HCs, the cytotoxicity and degranulation of NK cells against
      K562 were comparable. CD69 expressions were recovered to the normal levels in the
      remission phase. CONCLUSIONS: This study shows that circulating NK cells are
      activated and numerically increased, and they produced more IFN-gamma in scrub
      typhus patients.

PMID- 28750013
TI  - Determination of the residue levels of nicarbazin and combination nicarbazin
      narasin in broiler chickens after oral administration.
AB  - The depletion times of the anticoccidial nicarbazin administered individually and
      of nicarbazin and narasin administered in combination were evaluated by
      determining the presence and levels of 4,4'-dinitrocarbanilide (DNC), the marker
      residue for nicarbazin, and narasin residues in the muscle tissues of broiler
      chickens subjected to a pharmacological treatment. A high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) method was used. The results
      showed the presence of all anticoccidial residues; however, the DNC levels were
      higher when the nicarbazin was administered individually than when it was used in
      association with narasin throughout the experimental period. After six days of
      withdrawal, the DNC level following nicarbazin administration alone was lower
      than the maximum residue level (MRL) of 200 MUg kg-1. However, when the
      nicarbazin was co-administered with narasin, the concentrations of DNC were lower
      than the MRL after four days of withdrawal. These results may be justified
      because the dosage of nicarbazin, when administrated individually, is greater
      than when it is used in combination with narasin. The levels of narasin were
      lower than the MRL of 15 MUg kg-1 throughout the evaluation period. It was
      concluded that nicarbazin is rapidly metabolized from the broiler muscles up to
      six days of withdrawal since the DNC levels were lower than the maximum residue
      level (MRL) and the concentrations of narasin were lower than the MRL throughout
      the evaluation period.

PMID- 28750014
TI  - Heart rate variability in multibacillar leprosy: Linear and nonlinear analysis.
AB  - OBJECTIVE: To evaluate the heart rate variability (HRV) in patients with
      multibacillary leprosy using dynamic linear and nonlinear analysis. MATERIAL AND
      METHODS: Twenty-one leprosy patients (mean age: 39.14 +/-10.58 years) and 21
      healthy subjects (mean age: 36.24 +/- 12.64 years) completed the sample. Heart
      rate variability recording was performed by a Polar RS800 CX heart monitor during
      a period of 15 min in the supine position and 15 min in a sitting position.
      Analysis of HRV was performed by frequency domain from high frequency (HF) and
      low frequency (LF) spectral indexes in absolute and normalized units. The
      nonlinear analysis of HRV was calculated using symbolic analysis (0V%, 1V%, 2LV%
      and 2UV% indexes), Shannon entropy (SE) and normalized complexity index (NCI).
      RESULTS: Linear analysis: both groups showed higher HF values (p < 0.05) and
      smaller LF values (p < 0.05) in supine than in sitting position. The leprosy
      patients showed higher LF values (p < 0.05) and smaller HF values (p < 0.05)
      compared to the controls on supine position. Symbolic analysis: leprosy patients
      had higher 0V% values (p < 0.05), smaller 2LV% values (p < 0.05) and 2UV % values
      compared to healthy subjects on both positions. The 1V % had higher values (p <
      0.05) for leprosy patients than for controls in the sitting position. The control
      subjects had smaller 0V % values (p < 0.05), and higher 2UV % values (p < 0.05)
      in the supine position compared to the sitting position. Leprosy patients had
      higher 2UV index values (p < 0.05) in the supine position compared to the sitting
      position. In the complexity analysis, leprosy patients had smaller SE and NCI
      values (p < 0.05) than the control in the supine position. There was no
      difference between the SE and NCI values of leprosy and the control subjects in
      the sitting position. The control subjects had higher SE and NCI values (p <
      0.05) in the supine position than in the sitting position. CONCLUSION: Leprosy
      patients had higher sympathetic modulation and smaller vagal modulation than
      controls, indicating less HRV and cardiac modulation with lower complexity. The
      control group displayed significant HRV differences in response to position
      changes while leprosy patients had fewer HRV differences after the same postural
      change. An analysis of HRV with linear and non-linear dynamics proved to be a
      reliable method and promising for the investigation of autonomic dysfunction in
      patients with multibacillary leprosy.

PMID- 28750015
TI  - Accuracy of self-collected vaginal dry swabs using the Xpert human papillomavirus
      assay.
AB  - BACKGROUND: Polymerase chain reaction-based Xpert human papillomavirus (HPV)
      assay is a rapid test that detects high-risk HPV (hrHPV) infection. This point-of
      care test is usually performed by collecting a cervical specimen in a vial of
      PreservCyt(r) transport medium. We compared HPV test positivity and accuracy
      between self-collected sample with a dry swab (s-DRY) versus physician-collected
      cervical sampling using a broom like brush and immediate immersion in PreservCyt
      (dr-WET). METHODS: In this cross-sectional study, we recruited 150 women >= 18
      years old attending the colposcopy clinic in the University Hospital of Geneva.
      Each participant first self-collected a vaginal sample using a dry swab and then
      the physician collected a cervical specimen in PreservCyt. HPV analysis was
      performed with Xpert. Part of the PreservCyt-collected sample was used for hrHPV
      detection with the cobas(r) HPV test. HPV test positivity and performance of the
      two collection methods was compared. RESULTS: HPV positivity was 49.1% for s-DRY,
      41.8% for dr-WET and 46.2% for cobas. Good agreement was found between s-DRY and
      dr-WET samples (kappa+/-Standard error (SE) = 0.64+/-0.09,), particularly for low
      grade squamous intraepithelial lesions (LSIL+) (kappa+/-SE = 0.80+/-0.17).
      Excellent agreement was found between the two samples for HPV16 detection in
      general (kappa+/-SE = 0.91+/-0.09) and among LSIL+ lesions (kappa+/-SE = 1.00+/
      0.17). Sensitivities and specificities were, respectively, 84.2% and 47.1%(s
      DRY), 73.1% and 58.7%. (dr-WET) and 77.8% and 45.7% (cobas) for CIN2+ detection.
      The median delay between sampling and HPV analysis was 7 days for the Xpert HPV
      assay and 19 days for cobas. There were 36 (24.0%) invalid results among s-DRY
      samples and 4 (2.7%) among dr-WET (p = 0.001). Invalid results happened due to
      the long interval between collection and analysis. CONCLUSION: Self-collected
      vaginal dry swabs are a valid alternative to collecting cervical samples in
      PreservCyt solution for HPV testing with the Xpert HPV assay. IMPACT: HPV self
      collection with dry cotton swabs might assist in the implementation of an
      effective screening strategy in developing countries. TRIAL REGISTRATION:
      International Standard Randomized Controlled Trial Number Registry
      ISRCTN83050913.

PMID- 28750016
TI  - Intensity and duration of neutropenia relates to the development of oral
      mucositis but not odontogenic infection during chemotherapy for hematological
      malignancy.
AB  - BACKGROUND: D-index which combines the intensity and duration of neutropenia is
      reported as a tool for evaluating the dynamics of neutropenia. This study aimed
      to analyze the relationship between D-index and oral complications (i.e., oral
      mucositis [OM] and odontogenic infection [OI]) during chemotherapies for
      hematological malignancies. METHODS: A total of 421 chemotherapeutic courses in
      104 patients were analyzed. Chemotherapeutic courses in patients who finished all
      of the prophylactic dental treatments were defined as "treatment Finish".
      Chemotherapeutic courses in patients who did not finish prophylactic dental
      treatments were defined as "treatment not-Finish". OM was evaluated according to
      the Common Terminology Criteria for Adverse Events, version 4.0. D-index was
      compared between chemotherapeutic courses with versus without oral complications.
      RESULTS: D-index was significantly higher in chemotherapeutic courses with grade
      1 or 2 OM (p < 0.001) than courses without OM. In contrast, higher D-index did
      not relate to the development of OI (p = 0.18). The occurrence of OI (p < 0.001)
      but not OM (p = 0.56) during chemotherapy was significantly higher in
      chemotherapeutic courses without the completion of dental intervention.
      CONCLUSIONS: Higher D-index relates to the development of OM. In contrast, OI
      occurs due to untreated odontogenic foci, and its occurrence does not relate to
      higher D-index.

PMID- 28750017
TI  - Corticotropin-releasing factor receptor-1 modulates biomarkers of DNA oxidation
      in Alzheimer's disease mice.
AB  - Increased production of hydroxyl radical is the main source of oxidative damage
      in mammalian DNA that accumulates in Alzheimer's disease (AD). Reactive oxygen
      species (ROS) react with both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) to
      generate 8-hydroxy-2'-deoxyguanosine (8-OHdG), both of which can be measured in
      the urine. Knowledge of this pathway has positioned measurement of urine 8-OHdG
      as a reliable index of DNA oxidation and a potential biomarker target for
      tracking early cellular dysfunction in AD. Furthermore, epigenetic studies
      demonstrate decreased global DNA methylation levels (e.g. 5-methyl-2'
      deoxycytidine, 5-mdC) in AD tissues. Moreover, stress hormones can activate
      neuronal oxidative stress which will stimulate the release of additional stress
      hormones and result in damages to hippocampal neurons in the AD brain. Our
      previous work suggests that treating AD transgenic mice the type-1 corticotropin
      releasing factor receptor (CRFR1) antagonist, R121919, to reduce stress
      signaling, prevented onset of cognitive impairment, synaptic/dendritic loss and
      Abeta plaque accumulation. Therefore, to investigate whether levels of DNA
      oxidation can be impacted by the same therapeutic approach, urine levels of
      hydrogen peroxide, 8-OHdG, 5-mdC and total antioxidant capacity (TAC) were
      analyzed using an AD Tg mouse model. We found that Tg animals had an 80% increase
      in hydrogen peroxide levels compared to wild type (Wt) counterparts, an effect
      that could be dramatically reversed by the chronic administration with R121919. A
      significant decrease of 8-OHdG levels was observed in Tg mice treated with CRFR1
      antagonist. Collectively our data suggest that the beneficial effects of CRFR1
      antagonism seen in Tg mice may be mechanistically linked to the modulation of
      oxidative stress pathways.

PMID- 28750018
TI  - Pancreatic cancer cell/fibroblast co-culture induces M2 like macrophages that
      influence therapeutic response in a 3D model.
AB  - Pancreatic cancer (PC) remains one of the most challenging solid tumors to treat
      with a high unmet medical need as patients poorly respond to standard-of-care
      therapies. Prominent desmoplastic reaction involving cancer-associated
      fibroblasts (CAFs) and the immune cells in the tumor microenvironment (TME) and
      their cross-talk play a significant role in tumor immune escape and progression.
      To identify the key cellular mechanisms induce an immunosuppressive tumor
      microenvironment, we established 3D co-culture model with pancreatic cancer
      cells, CAFs and monocytes. Using this model, we analyzed the influence of tumor
      cells and fibroblasts on monocytes and their immune suppressive phenotype.
      Phenotypic characterization of the monocytes after 3D co-culture with
      tumor/fibroblast spheroids was performed by analyzing the expression of defined
      cell surface markers and soluble factors. Functionality of these monocytes and
      their ability to influence T cell phenotype and proliferation was investigated.
      3D co-culture of monocytes with pancreatic cancer cells and fibroblasts induced
      the production of immunosuppressive cytokines which are known to promote
      polarization of M2 like macrophages and myeloid derived suppressive cells
      (MDSCs). These co-culture spheroid polarized monocyte derived macrophages (MDMs)
      were poorly differentiated and had an M2 phenotype. The immunosuppressive
      function of these co-culture spheroids polarized MDMs was demonstrated by their
      ability to inhibit CD4+ and CD8+ T cell activation and proliferation in vitro,
      which we could partially reverse by 3D co-culture spheroid treatment with
      therapeutic molecules that are able to re-activated spheroid polarized MDMs or
      block immune suppressive factors such as Arginase-I.

PMID- 28750019
TI  - Comparison of activity and fatigue of the respiratory muscles and pulmonary
      characteristics between post-polio patients and controls: A pilot study.
AB  - OBJECTIVES: To compare pulmonary function measures, maximal respiratory pressure
      and fatigue of respiratory muscles between patients with Post-Polio Syndrome
      (PPS) and controls. DESIGN: Cross-sectional study. PATIENTS: Patients with PPS (N
      = 12; age 62.1+/-11.6 years) able to walk for 6 minutes without human assistance;
      age-matched controls with no history of polio or pulmonary dysfunction (N = 12;
      age 62.2+/-6.5 years). MEASUREMENTS: A body plethysmograph was used to quantify
      Residual Volume (RV), Total Lung Capacity (TLC), and Thoracic Gas Volume (TGV)
      etc. A manometer was used to measure Maximal Inspiratory Pressure (MIP) and
      Maximal Expiratory Pressure. A spirometer was used to measure Maximal Voluntary
      Ventilation (MVV). Surface electromyography (sEMG) recorded diaphragmatic muscle
      activity while performing MVV. RESULTS: The control group had significantly
      higher TGV and showed improvement in MIP following the effort (difference of
      5.5+/-4.0cmH2O) while the PPS group showed deterioration in MIP (difference of 
      2.5+/-5.0cmH2O). Subjects with scoliosis had significantly higher RV/TLC values
      compared with subjects without scoliosis. The 25th frequency percentile of the
      sEMG signal acquired during MVV was reduced in the PPS group. CONCLUSIONS:
      Maximal respiratory pressure test and sEMG measurements may identify fatigue of
      respiratory muscles in patients with PPS. Early diagnosis of respiratory
      impairment may delay respiratory decline and future need of invasive respiratory
      aids.

PMID- 28750020
TI  - Antibiotic prescriptions for outpatient acute rhinosinusitis in Canada, 2007
      2013.
AB  - INTRODUCTION: Acute rhinosinusitis (ARS) is a respiratory disease commonly caused
      by viral infections. Physicians regularly prescribe antibiotics despite bacterial
      etiologies being uncommon. This is of concern, as this use adds to the selection
      pressure for resistance. Here we present the descriptive epidemiology of acute
      rhinosinusitis and corresponding antibiotic prescribing practices by Canadian
      outpatient physicians from 2007-2013. MATERIALS/METHODS: Diagnosis and antibiotic
      prescription data for ARS were extracted from the Canadian Disease and
      Therapeutic Index for 2007 to 2013, and population data were acquired from
      Statistics Canada. ARS diagnosis and antibiotic prescription rates and
      frequencies of antibiotic classes were calculated. RESULTS: Eighty-eight percent
      of patients diagnosed with ARS in 2013 were adults, with a greater rate of
      antibiotic prescriptions observed among the adults relative to the pediatric
      patients (1632.9 and 468.6 antibiotic prescriptions per 10,000 inhabitants).
      Between 2007 and 2013, the ARS diagnosis rate decreased from 596 to 464 diagnoses
      per 10,000 inhabitants, while the percentage of diagnoses with antibiotic
      prescriptions at the national level remained stable (87% to 84%). From 2007 to
      2013, prescription rates for macrolides decreased from 203.5 to 105.4
      prescriptions per 10,000 inhabitants. In 2013, penicillins with extended spectrum
      were more commonly prescribed compared to macrolides among adult patients (153.5
      and 105.4 prescriptions per 10,000 inhabitants, respectively). CONCLUSION: This
      study is the first to describe physician antibiotic prescribing practices for
      treatment of ARS in Canada. Results show that antibiotic treatment for ARS
      represents an area for implementing antimicrobial stewardship, and through it,
      managing antibiotic resistance. Further work is required to better understand
      diagnosing practices and treatment criteria for ARS, and use this information to
      further assist physicians to limit unnecessary antibiotic prescribing practices.

PMID- 28750021
TI  - Dynamics and asymmetry in the dimer of the norovirus major capsid protein.
AB  - Noroviruses are the major cause of non-bacterial acute gastroenteritis in humans
      and livestock worldwide, despite being physically among the simplest animal
      viruses. The icosahedral capsid encasing the norovirus RNA genome is made of 90
      dimers of a single ca 60-kDa polypeptide chain, VP1, arranged with T = 3
      icosahedral symmetry. Here we study the conformational dynamics of this main
      building block of the norovirus capsid. We use molecular modeling and all-atom
      molecular dynamics simulations of the VP1 dimer for two genogroups with 50%
      sequence identity. We focus on the two points of flexibility in VP1 known from
      the crystal structure of the genogroup I (GI, human) capsid and from subsequent
      cryo-electron microscopy work on the GII capsid (also human). First, with a
      homology model of the GIII (bovine) VP1 dimer subjected to simulated annealing
      then classical molecular dynamics simulations, we show that the N-terminal arm
      conformation seen in the GI crystal structure is also favored in GIII VP1 but
      depends on the protonation state of critical residues. Second, simulations of the
      GI dimer show that the VP1 spike domain will not keep the position found in the
      GII electron microscopy work. Our main finding is a consistent propensity of the
      VP1 dimer to assume prominently asymmetric conformations. In order to probe this
      result, we obtain new SAXS data on GI VP1 dimers. These data are not
      interpretable as a population of symmetric dimers, but readily modeled by a
      highly asymmetric dimer. We go on to discuss possible implications of
      spontaneously asymmetric conformations in the successive steps of norovirus
      capsid assembly. Our work brings new lights on the surprising conformational
      range encoded in the norovirus major capsid protein.

PMID- 28750022
TI  - Determinants of operative time in thyroid surgery: A prospective multicenter
      study of 3454 thyroidectomies.
AB  - OBJECTIVE: To identify the determinants of operative time for thyroidectomy and
      quantify the relative influence of preoperative and intra-operative factors.
      BACKGROUND: Anticipation of operative time is key to avoid both waste of hospital
      resources and dissatisfaction of the surgical staff. Having an accurate and
      anticipated planning would allow a rationalized operating room use and may
      improve patient flow and staffing level. METHODS: We conducted a prospective,
      cross-sectional study between April 2008 and December 2009. The operative time of
      3454 patients who underwent thyroidectomy performed by 28 surgeons in five
      academic hospitals was monitored. We used multilevel linear regression to model
      determinants of operative time while accounting for the interplay of
      characteristics specific to surgeons, patients, and surgical procedures. The
      relative impact of each variable on operative time was estimated. RESULTS:
      Overall, 86% (99% CI 83 to 89) of operative time variation was related to
      preoperative variables. Surgeon characteristics accounted for 32% (99% CI 29 to
      35) of variation, center location for 29% (99% CI 25 to 33), and surgical
      procedure or patient variables for 24% (99% CI 20 to 27). Operative time was
      significantly lower among experienced surgeons having practiced from 5-19 years (
      21.8 min, P<0.05), performing at least 300 thyroidectomies per year (-28.8 min,
      P<0.05), and with increasing number of thyroidectomies performed the same day (
      11.7min, P<0.001). Conversely, operative time increased in cases of procedure
      supervision by a more experienced surgeon (+20.0 min, P<0.001). The remaining
      13.0% of variability was attributable to unanticipated technical difficulties at
      the time of surgery. CONCLUSIONS: Variation in thyroidectomy duration is largely
      explained by preoperative factors, suggesting that it can be accurately
      anticipated. Prediction tools allowing better regulation of patient flow in
      operating rooms appears feasible for both working conditions and cost management.

PMID- 28750023
TI  - The combination of the error correction methods of GAFCHROMIC EBT3 film.
AB  - PURPOSE: The aim of this study was to combine a set of methods for use of
      radiochromic film dosimetry, including calibration, correction for lateral
      effects and a proposed triple-channel analysis. These methods can be applied to
      GAFCHROMIC EBT3 film dosimetry for radiation field analysis and verification of
      IMRT plans. METHODS: A single-film exposure was used to achieve dose calibration,
      and the accuracy was verified based on comparisons with the square-field
      calibration method. Before performing the dose analysis, the lateral effects on
      pixel values were corrected. The position dependence of the lateral effect was
      fitted by a parabolic function, and the curvature factors of different dose
      levels were obtained using a quadratic formula. After lateral effect correction,
      a triple-channel analysis was used to reduce disturbances and convert scanned
      images from films into dose maps. The dose profiles of open fields were measured
      using EBT3 films and compared with the data obtained using an ionization chamber.
      Eighteen IMRT plans with different field sizes were measured and verified with
      EBT3 films, applying our methods, and compared to TPS dose maps, to check correct
      implementation of film dosimetry proposed here. RESULTS: The uncertainty of
      lateral effects can be reduced to +/-1 cGy. Compared with the results of Micke A
      et al., the residual disturbances of the proposed triple-channel method at 48,
      176 and 415 cGy are 5.3%, 20.9% and 31.4% smaller, respectively. Compared with
      the ionization chamber results, the difference in the off-axis ratio and
      percentage depth dose are within 1% and 2%, respectively. For the application of
      IMRT verification, there were no difference between two triple-channel methods.
      Compared with only corrected by triple-channel method, the IMRT results of the
      combined method (include lateral effect correction and our present triple-channel
      method) show a 2% improvement for large IMRT fields with the criteria 3%/3 mm.

PMID- 28750024
TI  - Applying time-frequency analysis to assess cerebral autoregulation during
      hypercapnia.
AB  - OBJECTIVE: Classic methods for assessing cerebral autoregulation involve a
      transfer function analysis performed using the Fourier transform to quantify
      relationship between fluctuations in arterial blood pressure (ABP) and cerebral
      blood flow velocity (CBFV). This approach usually assumes the signals and the
      system to be stationary. Such an presumption is restrictive and may lead to
      unreliable results. The aim of this study is to present an alternative method
      that accounts for intrinsic non-stationarity of cerebral autoregulation and the
      signals used for its assessment. METHODS: Continuous recording of CBFV, ABP, ECG,
      and end-tidal CO2 were performed in 50 young volunteers during normocapnia and
      hypercapnia. Hypercapnia served as a surrogate of the cerebral autoregulation
      impairment. Fluctuations in ABP, CBFV, and phase shift between them were tested
      for stationarity using sphericity based test. The Zhao-Atlas-Marks distribution
      was utilized to estimate the time-frequency coherence (TFCoh) and phase shift
      (TFPS) between ABP and CBFV in three frequency ranges: 0.02-0.07 Hz (VLF), 0.07
      0.20 Hz (LF), and 0.20-0.35 Hz (HF). TFPS was estimated in regions locally
      validated by statistically justified value of TFCoh. The comparison of TFPS with
      spectral phase shift determined using transfer function approach was performed.
      RESULTS: The hypothesis of stationarity for ABP and CBFV fluctuations and the
      phase shift was rejected. Reduced TFPS was associated with hypercapnia in the VLF
      and the LF but not in the HF. Spectral phase shift was also decreased during
      hypercapnia in the VLF and the LF but increased in the HF. Time-frequency method
      led to lower dispersion of phase estimates than the spectral method, mainly
      during normocapnia in the VLF and the LF. CONCLUSION: The time-frequency method
      performed no worse than the classic one and yet may offer benefits from lower
      dispersion of phase shift as well as a more in-depth insight into the dynamic
      nature of cerebral autoregulation.

PMID- 28750025
TI  - HIV drug resistance in HIV positive individuals under antiretroviral treatment in
      Shandong Province, China.
AB  - The efficacy of antiretroviral drugs is limited by the development of drug
      resistance. Therefore, it is important to examine HIV drug resistance following
      the nationwide implementation of drug resistance testing in China since 2009. We
      conducted drug resistance testing in patients who were already on or new to HIV
      antiretroviral therapy (ART) in Shandong Province, China, from 2011 to 2013, and
      grouped them based on the presence or absence of drug resistance to determine the
      effects of age, gender, ethnicity, marital status, educational level, route of
      transmission and treatment status on drug resistance. We then examined levels of
      drug resistance the following year. The drug resistance rates of HIV patients on
      ART in Shandong from 2011 to 2013 were 3.45% (21/608), 3.38% (31/916), and 4.29%
      (54/1259), per year, respectively. M184V was the most frequently found point
      mutation, conferring resistance to the nucleoside reverse transcriptase
      inhibitor, while Y181C, G190A, K103N and V179D/E/F were the most frequent point
      mutations conferring resistance to the non-nucleoside reverse transcriptase
      inhibitor. In addition, the protease inhibitor drug resistance mutations I54V and
      V82A were identified for the first time in Shandong Province. Primary resistance
      accounts for 20% of the impact factors for drug resistance. Furthermore, it was
      found that educational level and treatment regimen were high-risk factors for
      drug resistance in 2011 (P<0.05), while treatment regimen was a high risk factor
      for drug resistance in 2012 and 2013 (P<0.05). Among the 106 drug-resistant
      patients, 77 received immediate adjustment of treatment regimen following
      testing, and 69 (89.6%) showed a reduction in drug resistance the following year.
      HIV drug resistance has a low prevalence in Shandong Province. However, patients
      on second line ART regimens and those with low educational level need continuous
      monitoring. Active drug resistance testing can effectively prevent the
      development of drug resistance.

PMID- 28750026
TI  - Differences in biopsychosocial profiles of diabetes patients by level of
      glycaemic control and health-related quality of life: The Maastricht Study.
AB  - AIMS: Tailored, patient-centred innovations are needed in the care for persons
      with type 2 diabetes mellitus (T2DM), in particular those with insufficient
      glycaemic control. Therefore, this study sought to assess their biopsychosocial
      characteristics and explore whether distinct biopsychosocial profiles exist
      within this subpopulation, which differ in health-related quality of life
      (HRQoL). METHODS: Cross-sectional study based on data from The Maastricht Study,
      a population-based cohort study focused on the aetiology, pathophysiology,
      complications, and comorbidities of T2DM. We analysed associations and clustering
      of glycaemic control and HRQoL with 38 independent variables (i.e.
      biopsychosocial characteristics) in different subgroups and using descriptive
      analyses, latent class analysis (LCA), and logistic regressions. RESULTS:
      Included were 840 persons with T2DM, mostly men (68.6%) and with a mean age of
      62.6 (+/-7.7) years. Mean HbA1c was 7.1% (+/-3.2%); 308 patients (36.7%) had
      insufficient glycaemic control (HbA1c>7.0% [53 mmol/mol]). Compared to those with
      sufficient control, these patients had a significantly worse-off status on
      multiple biopsychosocial factors, including self-efficacy, income, education and
      several health-related characteristics. Two 'latent classes' were identified in
      the insufficient glycaemic control subgroup: with low respectively high HRQoL. Of
      the two, the low HRQoL class comprised about one-fourth of patients and had a
      significantly worse biopsychosocial profile. CONCLUSIONS: Insufficient glycaemic
      control, particularly in combination with low HRQoL, is associated with a
      generally worse biopsychosocial profile. Further research is needed into the
      complex and multidimensional causal pathways explored in this study, so as to
      increase our understanding of the heterogeneous care needs and preferences of
      persons with T2DM, and translate this knowledge into tailored care and support
      arrangements.

PMID- 28750027
TI  - Differential metabolic profiles associated to movement behaviour of stream
      resident brown trout (Salmo trutta).
AB  - The mechanisms that can contribute in the fish movement strategies and the
      associated behaviour can be complex and related to the physiology, genetic and
      ecology of each species. In the case of the brown trout (Salmo trutta), in recent
      research works, individual differences in mobility have been observed in a
      population living in a high mountain river reach (Pyrenees, NE Spain). The
      population is mostly sedentary but a small percentage of individuals exhibit a
      mobile behavior, mainly upstream movements. Metabolomics can reflect changes in
      the physiological process and can determine different profiles depending on
      behaviour. Here, a non-targeted metabolomics approach was used to find possible
      changes in the blood metabolomic profile of S. trutta related to its movement
      behaviour, using a minimally invasive sampling. Results showed a differentiation
      in the metabolomic profiles of the trouts and different level concentrations of
      some metabolites (e.g. cortisol) according to the home range classification
      (pattern of movements: sedentary or mobile). The change in metabolomic profiles
      can generally occur during the upstream movement and probably reflects the
      changes in metabolite profile from the non-mobile season to mobile season. This
      study reveals the contribution of the metabolomic analyses to better understand
      the behaviour of organisms.

PMID- 28750028
TI  - Clinical impact of a targeted next-generation sequencing gene panel for
      autoinflammation and vasculitis.
AB  - BACKGROUND: Monogenic autoinflammatory diseases (AID) are a rapidly expanding
      group of genetically diverse but phenotypically overlapping systemic inflammatory
      disorders associated with dysregulated innate immunity. They cause significant
      morbidity, mortality and economic burden. Here, we aimed to develop and evaluate
      the clinical impact of a NGS targeted gene panel, the "Vasculitis and
      Inflammation Panel" (VIP) for AID and vasculitis. METHODS: The Agilent SureDesign
      tool was used to design 2 versions of VIP; VIP1 targeting 113 genes, and a later
      version, VIP2, targeting 166 genes. Captured and indexed libraries (QXT Target
      Enrichment System) prepared for 72 patients were sequenced as a multiplex of 16
      samples on an Illumina MiSeq sequencer in 150bp paired-end mode. The cohort
      comprised 22 positive control DNA samples from patients with previously validated
      mutations in a variety of the genes; and 50 prospective samples from patients
      with suspected AID in whom previous Sanger based genetic screening had been non
      diagnostic. RESULTS: VIP was sensitive and specific at detecting all the
      different types of known mutations in 22 positive controls, including gene
      deletion, small INDELS, and somatic mosaicism with allele fraction as low as 3%.
      Six/50 patients (12%) with unclassified AID had at least one class 5 (clearly
      pathogenic) variant; and 11/50 (22%) had at least one likely pathogenic variant
      (class 4). Overall, testing with VIP resulted in a firm or strongly suspected
      molecular diagnosis in 16/50 patients (32%). CONCLUSIONS: The high diagnostic
      yield and accuracy of this comprehensive targeted gene panel validate the use of
      broad NGS-based testing for patients with suspected AID.

PMID- 28750029
TI  - Ubiquinol-cytochrome c reductase core protein 1 may be involved in delayed
      cardioprotection from preconditioning induced by diazoxide.
AB  - This study aimed to use long-term diazoxide treatment to establish a loss-of
      cardioprotection model and then perform proteomics analysis to explore which
      proteins of mitochondrial inner membrane (MIM) are potentially involved in
      delayed cardioprotection. Rats received 1 to 8 weeks of diazoxide treatments (20
      mg*kg-1*d-1) to establish a loss-of-cardioprotection model in different groups.
      Detection of serum cTnI levels and cell apoptosis assays in heart tissue were
      performed. Then, rats MIM after 0, 4 and 6 weeks of diazoxide treatment was
      isolated and proteomics analysis was performed. An invitro model of H9C2 cells
      was performed to explore the effects of targeted protein on delayed
      cardioprotection. The effect of delayed cardioprotection by diazoxide
      preconditioning disappeared when diazoxide treatments were given for six weeks or
      longer. Ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) was identified
      in the proteomics analysis. UQCRC1 expression was upregulated by diazoxide
      treatment in H9C2 cells, and UQCRC1 down-regulation could increase the lactate
      dehydrogenase release and apoptosis rate after injury induced by oxygen glucose
      deprivation. These results showed that UQCRC1 might contribute to the loss-of
      cardioprotection model induced by long-term diazoxide treatment and play a role
      in delayed cardioprotection.

PMID- 28750030
TI  - Minimally inconsistent reasoning in Semantic Web.
AB  - Reasoning with inconsistencies is an important issue for Semantic Web as
      imperfect information is unavoidable in real applications. For this, different
      paraconsistent approaches, due to their capacity to draw as nontrivial
      conclusions by tolerating inconsistencies, have been proposed to reason with
      inconsistent description logic knowledge bases. However, existing paraconsistent
      approaches are often criticized for being too skeptical. To this end, this paper
      presents a non-monotonic paraconsistent version of description logic reasoning,
      called minimally inconsistent reasoning, where inconsistencies tolerated in the
      reasoning are minimized so that more reasonable conclusions can be inferred. Some
      desirable properties are studied, which shows that the new semantics inherits
      advantages of both non-monotonic reasoning and paraconsistent reasoning. A
      complete and sound tableau-based algorithm, called multi-valued tableaux, is
      developed to capture the minimally inconsistent reasoning. In fact, the tableaux
      algorithm is designed, as a framework for multi-valued DL, to allow for different
      underlying paraconsistent semantics, with the mere difference in the clash
      conditions. Finally, the complexity of minimally inconsistent description logic
      reasoning is shown on the same level as the (classical) description logic
      reasoning.

PMID- 28750031
TI  - Dissecting the proteome dynamics of the salt stress induced changes in the leaf
      of diploid and autotetraploid Paulownia fortunei.
AB  - Exposure to high salinity can trigger acclimation in many plants. Such an
      adaptative response is greatly advantageous for plants and involves extensive
      reprogramming at the molecular level. Acclimation allows plants to survive in
      environments that are prone to increasing salinity. In this study, diploid and
      autotetraploid Paulownia fortunei seedlings were used to detect alterations in
      leaf proteins in plants under salt stress. Up to 152 differentially abundant
      proteins were identified by Multiplex run iTRAQ-based quantitative proteomic and
      LC-MS/MS methods. Bioinformatics analysis suggested that P. fortunei leaves
      reacted to salt stress through a combination of common responses, such as induced
      metabolism, signal transduction, and regulation of transcription. This study
      offers a better understanding of the mechanisms of salt tolerance in P. fortunei
      and provides a list of potential target genes that could be engineered for salt
      acclimation in plants, especially trees.

PMID- 28750032
TI  - Spatial characteristics and the epidemiology of human infections with avian
      influenza A(H7N9) virus in five waves from 2013 to 2017 in Zhejiang Province,
      China.
AB  - BACKGROUND: The five-wave epidemic of H7N9 in China emerged in the second half of
      2016. This study aimed to compare the epidemiological characteristics among the
      five waves, estimating the possible infected cases and inferring the extent of
      the possible epidemic in the areas that have not reported cases before. METHODS:
      The data for the H7N9 cases from Zhejiang Province between 2013 and 2017 was
      obtained from the China Information Network System of Disease Prevention and
      Control. The start date of each wave was 16 March 2013, 1 July 2013, 1 July 2014,
      1 July 2015 and 1 July 2016. The F test or Pearson's chi-square test were used to
      compare the characteristics of the five waves. Global and local autocorrelation
      analysis was carried out to identify spatial autocorrelations. Ordinary kriging
      interpolation was analyzed to estimate the number of human infections with H7N9
      virus and to infer the extent of infections in the areas with no cases reported
      before. RESULT: There were 45, 94, 45, 34 and 80 cases identified from the first
      wave to the fifth, respectively. The death rate was significantly different among
      the five waves of epidemics (chi2 = 10.784, P = 0.029). The age distribution (F =
      0.903, P = 0.462), gender (chi2 = 2.674, P = 0.614) and occupation(chi2 = 19.764,
      P = 0.407) were similar in each period. Most of the cases were males and farmers.
      A significant trend (chi2 = 70.328, P<0.001) was identified that showed a growing
      proportion of rural cases. There were 31 high-high clusters and 3 high-low
      clusters at the county level among the five waves and 12, 8, 2, 9 and 3 clusters
      in each wave, respectively. The total cases infected with the H7N9 virus were far
      more than those that have been reported now, and the affected areas continue to
      expand. The epidemic in the north of Zhejiang Province persisted in all five
      waves. Since the second wave, the virus spread to the south areas and central
      areas. There was an obvious decline in the infected cases in the urban areas, and
      the epidemics mostly occurred in the rural areas after the fourth wave. The
      epidemic was relatively dispersed since the third wave had fewer than two cases
      in most of the areas and showed a reinforcing trend again in the fifth wave.
      CONCLUSIONS: The study revealed that there were few differences in the
      epidemiologic characteristics among the five waves of the epidemic. However, the
      areas where the possible epidemic circulated was larger than reported. The
      epidemic cross-regional expansion continued and mostly occurred in rural areas.
      Continuous closure of the live poultry market (LPM) is strongly recommended in
      both rural and urban areas. Illegal and scattered live poultry trading,
      especially in rural areas, must be forbidden. It is suggested too that a more
      rigorous management be performed on live poultry trade and wholesale across the
      area. Health education, surveillance of cases and pathogenicity should also be
      strengthened.

PMID- 28750033
TI  - Analysis of the developmental stages, kinetics, and phenotypes exhibited by
      myeloid cells driven by GM-CSF in vitro.
AB  - The developmental progression of conventional DC has been quite well defined, yet
      the developmental pathway of monocyte-derived, GM-CSF-driven DC is less well
      understood. We addressed this issue by establishing an isolation strategy that
      identifies five distinct GM-CSF derived cell types. Expression of Ly6C and CD115
      (Csf-1R) was used to identify and isolate four populations. One of the
      populations could be further separated based on CD11c expression, distinguishing
      five populations. We further defined these cells based on expression of
      transcription factors and markers of early and later stages of myeloid
      development. These discreet developmental stages corresponded well with
      previously defined populations: Common Myeloid Progenitors (CMP),
      Granulocyte/Macrophage Progenitors (GMP), Monocytes, as well as Monocyte-derived
      macrophages (moMac) and Monocyte-derived DC (moDC). Finally, within the moMac
      population we also identified moDC precursor activity (moDP) that could be
      distinguished from moMac and moDC based on their level of MHC class II expression
      and developmental plasticity.

PMID- 28750034
TI  - A modified FASP protocol for high-throughput preparation of protein samples for
      mass spectrometry.
AB  - To facilitate high-throughput proteomic analyses we have developed a modified
      FASP protocol which improves the rate at which protein samples can be processed
      prior to mass spectrometry. Adapting the original FASP protocol to a 96-well
      format necessitates extended spin times for buffer exchange due to the low
      centrifugation speeds tolerated by these devices. However, by using 96-well
      plates with a more robust polyethersulfone molecular weight cutoff membrane,
      instead of the cellulose membranes typically used in these devices, we could use
      isopropanol as a wetting agent, decreasing spin times required for buffer
      exchange from an hour to 30 minutes. In a typical work flow used in our
      laboratory this equates to a reduction of 3 hours per plate, providing processing
      times similar to FASP for the processing of up to 96 samples per plate. To test
      whether our modified protocol produced similar results to FASP and other FASP
      like protocols we compared the performance of our modified protocol to the
      original FASP and the more recently described eFASP and MStern-blot. We show that
      all FASP-like methods, including our modified protocol, display similar
      performance in terms of proteins identified and reproducibility. Our results show
      that our modified FASP protocol is an efficient method for the high-throughput
      processing of protein samples for mass spectral analysis.

PMID- 28750035
TI  - The modulation of EEG variability between internally- and externally-driven
      cognitive states varies with maturation and task performance.
AB  - Increasing evidence suggests that brain signal variability is an important
      measure of brain function reflecting information processing capacity and
      functional integrity. In this study, we examined how maturation from childhood to
      adulthood affects the magnitude and spatial extent of state-to-state transitions
      in brain signal variability, and how this relates to cognitive performance. We
      looked at variability changes between resting-state and task (a symbol-matching
      task with three levels of difficulty), and within trial (fixation, post-stimulus,
      and post-response). We calculated variability with multiscale entropy (MSE), and
      additionally examined spectral power density (SPD) from electroencephalography
      (EEG) in children aged 8-14, and in adults aged 18-33. Our results suggest that
      maturation is characterized by increased local information processing (higher MSE
      at fine temporal scales) and decreased long-range interactions with other neural
      populations (lower MSE at coarse temporal scales). Children show MSE changes that
      are similar in magnitude, but greater in spatial extent when transitioning
      between internally- and externally-driven brain states. Additionally, we found
      that in children, greater changes in task difficulty were associated with greater
      magnitude of modulation in MSE. Our results suggest that the interplay between
      maturational and state-to-state changes in brain signal variability manifest
      across different spatial and temporal scales, and influence information
      processing capacity in the brain.

PMID- 28750036
TI  - Generation and phenotypic characterization of Pde1a mutant mice.
AB  - It has been proposed that a reduction in intracellular calcium causes an increase
      in intracellular cAMP and PKA activity through stimulation of calcium inhibitable
      adenylyl cyclase 6 and inhibition of phosphodiesterase 1 (PDE1), the main enzymes
      generating and degrading cAMP in the distal nephron and collecting duct, thus
      contributing to the development and progression of autosomal dominant polycystic
      kidney disease (ADPKD). In zebrafish pde1a depletion aggravates and
      overexpression ameliorates the cystic phenotype. To study the role of PDE1A in a
      mammalian system, we used a TALEN pair to Pde1a exon 7, targeting the histidine
      aspartic acid dipeptide involved in ligating the active site Zn++ ion to generate
      two Pde1a null mouse lines. Pde1a mutants had a mild renal cystic disease and a
      urine concentrating defect (associated with upregulation of PDE4 activity and
      decreased protein kinase A dependent phosphorylation of aquaporin-2) on a wild
      type genetic background and aggravated renal cystic disease on a Pkd2WS25/-
      background. Pde1a mutants additionally had lower aortic blood pressure and
      increased left ventricular (LV) ejection fraction, without a change in LV mass
      index, consistent with the high aortic and low cardiac expression of Pde1a in
      wild-type mice. These results support an important role of PDE1A in the renal
      pathogenesis of ADPKD and in the regulation of blood pressure.

PMID- 28750037
TI  - Generation and characterization of interferon-lambda 1-resistant H1N1 influenza A
      viruses.
AB  - Influenza A viruses pose a constant potential threat to human health. In view of
      the innate antiviral activity of interferons (IFNs) and their potential use as
      anti-influenza agents, it is important to know whether viral resistance to these
      antiviral proteins can arise. To examine the likelihood of emergence of IFN
      lambda1-resistant H1N1 variants, we serially passaged the A/California/04/09
      (H1N1) strain in a human lung epithelial cell line (Calu-3) in the presence of
      increasing concentrations of recombinant IFN-lambda1 protein. To monitor changes
      associated with adaptation of this virus to growth in Calu-3 cells, we also
      passaged the wild-type virus in the absence of IFN-lambda1. Under IFN-lambda1
      selective pressure, the parental virus developed two neuraminidase (NA)
      mutations, S79L and K331N, which significantly reduced NA enzyme activity (?1.4
      fold) and sensitivity to IFN-lambda1 (??20-fold), respectively. These changes
      were not associated with a reduction in viral replication levels. Mutants
      carrying either K331N alone or S79L and K331N together induced weaker
      phosphorylation of IFN regulatory factor 3 (IRF3), and, as a consequence, much
      lower expression of the IFN genes (IFNB1, IFNL1 and IFNL2/3) and proteins (IFN
      lambda1 and IFN-lambda2/3). The lower levels of IFN expression correlated with
      weaker induction of tyrosine-phosphorylated STAT1 and reduced RIG-I protein
      levels. Our findings demonstrate that influenza viruses can develop increased
      resistance to the antiviral activity of type III interferons.

PMID- 28750038
TI  - Low calcium diet increases 4T1 mammary tumor carcinoma cell burden and bone
      pathology in mice.
AB  - Breast cancer metastasizes to bone in the majority of patients with advanced
      disease. We investigated the effects of inadequate dietary calcium (Ca) on bone
      turnover, tumor growth, and bone response to tumor in tibia inoculated with 4T1
      mammary carcinoma cells. Nine-month-old female Balb/c mice were placed on an
      adequate Ca (5 g/kg diet, n = 30) or low Ca (80 mg/kg diet, n = 31) diet for 14
      days, then injected intratibially with 1,000 4T1 cells (transfected with
      luciferase for bioluminescence imaging), and sacrificed at 5, 10, or 21 days post
      inoculation (n = 7-10 mice/group). Control mice (n = 6/group) were injected with
      carrier and sacrificed at 10 days post-inoculation. Tibiae with muscle intact
      were excised and evaluated by microcomputed tomography and histology. In vivo
      bioluminescent imaging revealed that 4T1 cells metastasized to lung. Therefore,
      lungs were removed for quantification of tumor. Mice fed low Ca exhibited higher
      bone turnover and higher tibial lesion scores than mice fed adequate Ca. Lesion
      severity, manifested as cortical osteolysis and periosteal woven bone formation,
      and tumor cell infiltration to muscle, increased with time, irrespective of diet.
      However, for most skeletal endpoints the rates of increase were greater in mice
      consuming low Ca compared to mice consuming adequate Ca. Infiltration of tumor
      cells into adjacent muscle, but not metastasis to lung, was also greater in mice
      consuming low Ca diet. The findings suggest that high bone turnover due to Ca
      insufficiency results in greater local mammary tumor cell growth, cortical
      osteolysis, woven bone formation, and invasion to muscle in mice.

PMID- 28750039
TI  - Resistance to the crayfish plague, Aphanomyces astaci (Oomycota) in the
      endangered freshwater crayfish species, Austropotamobius pallipes.
AB  - The pathogen Aphanomyces astaci Schikora 1906 is responsible for the decline of
      the native crayfish species of Europe, and their current endangered status. This
      pathogenic species is native to North America and only colonizes aquatic
      decapods. The North American crayfish species have a high resistance to this
      pathogen, while species from other regions are highly susceptible. However,
      recent field and laboratory observations indicate that there might exist some
      populations with resistance against this disease. The objective of this study was
      to test the susceptibility of 8 selected native European crayfish populations of
      Austropotamobius pallipes Lereboullet 1858 from the Pyrenees. We challenged them
      against the genome sequenced strain AP03 of A. astaci isolated from a North
      American red swamp crayfish, Procambarus clarkii Girard 1852, in the Garrotxa
      Natural Park, Girona. The results showed that there are significant differences
      (P<0,001) among populations, although most of them show high mortality rates
      after the zoospore challenge with A. astaci. However, one population from Girona
      exhibited a 100% survival during a four-month monitoring period under the
      experimental conditions tested. Histological analyses revealed a high immune
      reaction in tissues examined, i.e., encapsulation and melanization of hyphae,
      similar to that found in North American resistant crayfish species. These results
      represent the first observation of a native European crayfish population showing
      high resistance towards the most virulent genotype of this pathogen, i.e.,
      genotype Pc. The identification of this population is of key importance for the
      management of these endangered species, and represents a crucial step forward
      towards the elucidation of the factors involved in the immune reaction against
      this devastating pathogen.

PMID- 28750040
TI  - Oral administration of live- or heat-killed Candida albicans worsened cecal
      ligation and puncture sepsis in a murine model possibly due to an increased serum
      (1->3)-beta-D-glucan.
AB  - Candida albicans is the most common fungus in the human intestinal microbiota but
      not in mice. To make a murine sepsis model more closely resemble human sepsis and
      to explore the role of intestinal C. albicans, in the absence of candidemia, in
      bacterial sepsis, live- or heat-killed C. albicans was orally administered to
      mice at 3h prior to cecal ligation and puncture (CLP). A higher mortality rate of
      CLP was demonstrated with Candida-administration (live- or heat-killed) prior to
      CLP. Fecal Candida presented only in experiments with live-Candida
      administration. Despite the absence of candidemia, serum (1->3)-beta-D-glucan
      (BG) was higher in CLP with Candida-administration than CLP-controls (normal
      saline administration) at 6h and/or 18h post-CLP. Interestingly, fluconazole
      attenuated the fecal Candida burden and improved survival in mice with live
      Candida administration, but not CLP-control. Microbiota analysis revealed
      increased Bacteroides spp. and reduced Lactobacillus spp. in feces after Candida
      administration. Additionally, synergy in the elicitation of cytokine production
      from bone marrow-derived macrophages, in vitro, was demonstrated by co-exposure
      to heat-killed E. coli and BG. In conclusion, intestinal abundance of fungi
      and/or fungal-molecules was associated with increased bacterial sepsis-severity,
      perhaps through enhanced cytokine elicitation induced by synergistic responses to
      molecules from gut-derived bacteria and fungi. Conversely, reducing intestinal
      fungal burdens decreased serum BG and attenuated sepsis in our model.

PMID- 28750041
TI  - Comparison of growth and physiological characteristics between roughstalk
      bluegrass and tall fescue in response to simulated waterlogging.
AB  - Roughstalk bluegrass (Poa trivialis) is a weed in cool season grass seed
      production fields in Oregon. Populations of this weed are often greater in fields
      prone to waterlogging. A greenhouse study was conducted to investigate the
      morphological and physiological differences between recently established
      roughstalk bluegrass and tall fescue (Lolium arundinaceum) plants in response to
      simulated waterlogging. Differences in root morphological development and root
      respiration were found between waterlogged tall fescue and roughstalk bluegrass.
      Plants after 4 weeks of waterlogging, leaf number, plant height, and root biomass
      were reduced more in tall fescue than in roughstalk bluegrass plants. The root
      length increased 6% in waterlogged tall fescue plants, and decreased 42% in
      waterlogged roughstalk bluegrass plants, which lead to a shallower root system in
      roughstalk bluegrass. Root aerenchyma area increased more in waterlogged
      roughstalk bluegrass than in tall fescue. Alcohol dehydrogenase and lactate
      dehydrogenase activities increased in the roots of both species, but not in the
      leaves. The increases were greater in tall fescue than in roughstalk bluegrass.
      Turf quality, aboveground biomass, photosynthetic capacity, and water-soluble
      carbohydrate concentrations were reduced by waterlogging, but there were no
      differences over time or species. Thus, the shallower root system, larger
      aerenchyma, and reduced fermentation rates were the characteristics most likely
      to contribute to better waterlogging tolerance in roughstalk bluegrass compared
      to tall fescue and invasion of roughstalk bluegrass in waterlogged cool season
      grass seed fields.

PMID- 28750042
TI  - Subclinical thyroid dysfunction and risk of carotid atherosclerosis.
AB  - BACKGROUND: The effect of subclinical thyroid dysfunction on vascular
      atherosclerosis remains uncertain. The objective of this study was to elucidate
      the association between sustained subclinical thyroid dysfunction and carotid
      plaques, which are an early surrogate marker of systemic atherosclerosis.
      METHODS: The study included 21,342 adults with consistent thyroid hormonal status
      on serial thyroid function tests (TFTs) and carotid artery duplex ultrasonography
      at a health screening center between 2007 and 2014. The effect of subclinical
      thyroid dysfunction on baseline carotid plaques and newly developed carotid
      plaques during 5-year follow-up was determined by logistic regression analyses
      and GEE (Generalized Estimating Equations), respectively. RESULTS: Carotid
      plaques were more common in the subclinical hypothyroidism (55.6%) than the
      euthyroidism (47.8%) at baseline. However, in multivariable analysis, thyroid
      status was not a significant risk for the carotid plaques at baseline. Instead,
      traditional cardiovascular risk factors, such as age (P <0.001), systolic blood
      pressure (P = 0.023), fasting blood glucose (P = 0.030), and creatinine (P =
      0.012) were associated with baseline carotid plaques in subclinical
      hypothyroidism. In longitudinal analyses of subjects who were followed up for
      more than 5 years, there was no significant difference in the cumulative
      incidence of new carotid plaques according to time between subjects with
      subclinical hypothyroidism and those with euthyroidism (P = 0.392). CONCLUSIONS:
      Sustained subclinical thyroid dysfunction did not affect the baseline or
      development of carotid plaques in healthy individuals.

PMID- 28750043
TI  - Correction: Adiponectin attenuates high glucose-induced apoptosis through the
      AMPK/p38 MAPK signaling pathway in NRK-52E cells.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178215.].

PMID- 28750044
TI  - HCV replication in gastrointestinal mucosa: Potential extra-hepatic viral
      reservoir and possible role in HCV infection recurrence after liver
      transplantation.
AB  - PURPOSE: Hepatitis C virus (HCV) predominantly infects hepatocytes, although it
      is known that receptors for viral entry are distributed on a wide array of target
      cells. Chronic HCV infection is indeed characterized by multiple non-liver
      manifestations, suggesting a more complex HCV tropism extended to extrahepatic
      tissues and remains to be fully elucidated. In this study, we investigated the
      gastrointestinal mucosa (GIM) as a potential extrahepatic viral replication site
      and its contribution to HCV recurrence. METHODS: We analyzed GIM biopsies from a
      cohort of 76 patients, 11 of which were HCV-negative and 65 HCV-positive. Of
      these, 54 biopsies were from liver-transplanted patients. In 29 cases, we were
      able to investigate gastrointestinal biopsies from the same patient before and
      after transplant. To evaluate the presence of HCV, we looked for viral antigens
      and genome RNA, whilst to assess viral replicative activity, we searched for the
      replicative intermediate minus-strand RNA. We studied the genetic diversity and
      the phylogenetic relationship of HCV quasispecies from plasma, liver and
      gastrointestinal mucosa of HCV-liver-transplanted patients in order to assess HCV
      compartmentalization and possible contribution of gastrointestinal variants to
      liver re-infection after transplantation. RESULTS: Here we show that HCV infects
      and replicates in the cells of the GIM and that the favorite hosts were mostly
      enteroendocrine cells. Interestingly, we observed compartmentalization of the HCV
      quasispecies present in the gastrointestinal mucosa compared to other tissues of
      the same patient. Moreover, the phylogenetic analysis revealed a high similarity
      between HCV variants detected in gastrointestinal mucosa and those present in the
      re-infected graft. CONCLUSIONS: Our results demonstrated that the
      gastrointestinal mucosa might be considered as an extrahepatic reservoir of HCV
      and that could contribute to viral recurrence. Moreover, the finding that HCV
      infects and replicates in neuroendocrine cells opens new perspectives on the role
      of these cells in the natural history of HCV infection.

PMID- 28750045
TI  - Effect of maternal obesity on birthweight and neonatal fat mass: A prospective
      clinical trial.
AB  - OBJECTIVE: To discriminate the effect of maternal obesity and gestational
      diabetes on birth weight and adipose tissue of the newborn. METHODS: Normal BMI
      women (group N, n = 243; 18.5<= BMI<25 kg/m2) and obese women (group Ob, n = 253;
      BMI>=30 kg/m2) were recruited in a prospective study between 15 and 18 weeks of
      gestation. All women were submitted to a 75g oral glucose tolerance test in the
      second and third trimester. First trimester fasting blood glucose was also
      obtained from Ob women. All women with one measurement above normal values were
      considered positive for gestational diabetes and first treated by dietary
      intervention. When dietary measures were not efficient, they were treated by
      insulin. Neonatal anthropometrics, sum of skinfolds and cord serum hormones were
      measured. RESULTS: 222 N and 226 Ob mothers and their newborns were included in
      the analysis. Diabetes was diagnosed in 20% and 45.2% of N and Ob women,
      respectively. Birth weight was not statistically different between groups (boys:
      3456g+/-433 and 3392g+/-463; girls: 3316g+/-402 and 3391g+/-408 for N and Ob,
      respectively). Multivariate analysis demonstrated that skinfold thickness and
      serum leptin concentrations were significantly increased in girls born to women
      with obesity (18.0mm+/-0.6 versus 19.7mm+/-0.5, p = 0.004 and 11.3ng/mL+/-1.0
      versus 15.3ng/mL+/-1.0, p = 0.02), but not in boys (18.4mm+/-0.6 versus 18.5mm+/
      0.5, p = 0.9 and 9.3ng/mL+/-1.0 versus 9.0ng/mL+/-1.0, p = 0.9). Based on data
      from 136 N and 124 Ob women, maternal insulin resistance at 37 weeks was also
      positively related to skinfold in girls, only, with a 1-point increase in HOMA-IR
      corresponding to a 0.33mm+/-0.08 increase in skinfold (p<0.0001). CONCLUSIONS:
      Regardless of gestational diabetes, maternal obesity and insulin resistance were
      associated with increased adiposity in girls only. Persistence of this sexual
      dimorphism remains to be explored during infancy.

PMID- 28750046
TI  - Wnt/beta-catenin signaling suppresses expressions of Scx, Mkx, and Tnmd in tendon
      derived cells.
AB  - After tendon injuries, biomechanical properties of the injured tendon are not
      fully recovered in most cases. Modulation of signaling pathways, which are
      involved in tendon development and tendon repair, is one of attractive modalities
      to facilitate proper regeneration of the injured tendon. The roles of TGF-beta
      signaling in tendon homeostasis and tendon development have been elucidated. In
      contrast, the roles of Wnt/beta-catenin signaling in tendon remain mostly
      elusive. We found that the number of beta-catenin-positive cells was increased at
      the injured site, suggesting involvement of Wnt/beta-catenin signaling in tendon
      healing. Activation of Wnt/beta-catenin signaling suppressed expressions of
      tenogenic genes of Scx, Mkx, and Tnmd in rat tendon-derived cells (TDCs) isolated
      from the Achilles tendons of 6-week old rats. Additionally, activation of
      Wnt/beta-catenin reduced the amounts of Smad2 and Smad3, which are intracellular
      mediators for TGF-beta signaling, and antagonized upregulation of Scx induced by
      TGF-beta signaling in TDCs. We found that Wnt/beta-catenin decreased Mkx and Tnmd
      expressions without suppressing Scx expression in Scx-programmed tendon
      progenitors. Our studies suggest that Wnt/beta-catenin signaling is a repressor
      for tenogenic gene expressions.

PMID- 28750047
TI  - Human cytomegalovirus IE1 downregulates Hes1 in neural progenitor cells as a
      potential E3 ubiquitin ligase.
AB  - Congenital human cytomegalovirus (HCMV) infection is the leading cause of
      neurological disabilities in children worldwide, but the mechanisms underlying
      these disorders are far from well-defined. HCMV infection has been shown to
      dysregulate the Notch signaling pathway in human neural progenitor cells (NPCs).
      As an important downstream effector of Notch signaling, the transcriptional
      regulator Hairy and Enhancer of Split 1 (Hes1) is essential for governing NPC
      fate and fetal brain development. In the present study, we report that HCMV
      infection downregulates Hes1 protein levels in infected NPCs. The HCMV 72-kDa
      immediate-early 1 protein (IE1) is involved in Hes1 degradation by assembling a
      ubiquitination complex and promoting Hes1 ubiquitination as a potential E3
      ubiquitin ligase, followed by proteasomal degradation of Hes1. Sp100A, an
      important component of PML nuclear bodies, is identified to be another target of
      IE1-mediated ubiquitination. A C-terminal acidic region in IE1, spanning amino
      acids 451 to 475, is required for IE1/Hes1 physical interaction and IE1-mediated
      Hes1 ubiquitination, but is dispensable for IE1/Sp100A interaction and
      ubiquitination. Our study suggests a novel mechanism linking downregulation of
      Hes1 protein to neurodevelopmental disorders caused by HCMV infection. Our
      findings also complement the current knowledge of herpesviruses by identifying
      IE1 as the first potential HCMV-encoded E3 ubiquitin ligase.

PMID- 28750048
TI  - Competition is the basis of the transport mechanism of the NhaB Na+/H+ exchanger
      from Klebsiella pneumoniae.
AB  - Na+/H+ exchange is essential for survival of all organisms, having a role in the
      regulation of the intracellular Na+ concentration, pH and cell volume.
      Furthermore, Na+/H+ exchangers were shown to be involved in the virulence of the
      bacterium Yersinia pestis, indicating they might be potential targets for novel
      antibiotic treatments. The model system for Na+/H+ exchangers is the NhaA
      transporter from Escherichia coli, EcNhaA. Therefore, the general transport
      mechanism of NhaA exchangers is currently well characterized. However, much less
      is known about NhaB exchangers, with only a limited number of studies available.
      The pathogen Klebsiella pneumoniae, which is a major source of nosocomial
      infection, possesses three electrogenic Na+/H+ exchangers, KpNhaA1, KpNhaA2 and
      KpNhaB, none of which have been previously investigated. Our aim in this study
      was to functionally characterize KpNhaB using solid supported membrane-based
      electrophysiology as the main investigation technique, and thus provide the first
      electrophysiological investigation of an NhaB Na+/H+ exchanger. We found that
      NhaB can be described by the same competition-based mechanism that was shown to
      be valid for electrogenic NhaA and NapA, and for electroneutral NhaP Na+/H+
      exchangers. For comparison we also characterized the activity of KpNhaA1 and
      KpNhaA2 and found that the three exchangers have complementary activity profiles,
      which is likely a survival advantage for K. pneumoniae when faced with
      environments of different salinity and pH. This underlines their importance as
      potential antibiotic drug targets.

PMID- 28750049
TI  - Genome Target Evaluator (GTEvaluator): A workflow exploiting genome dataset to
      measure the sensitivity and specificity of genetic markers.
AB  - Most of the bacterial typing methods used to discriminate isolates in medical or
      food safety microbiology are based on genetic markers used as targets in PCR or
      hybridization experiments. These DNA typing methods are important tools for
      studying prevalence and epidemiology, for conducting surveillance, investigations
      and control of biological hazard sources. In that perspective, it is crucial to
      insure that the chosen genetic markers have the greatest specificity and
      sensitivity. The wealth of whole-genome sequences available for many bacterial
      species offers the opportunity to evaluate the performance of these genetic
      markers. In the present study, we have developed GTEvaluator, a bioinformatics
      workflow which ranks genetic markers depending on their sensitivity and
      specificity towards groups of well-defined genomes. GTEvaluator identifies the
      most performant genetic markers to target individuals among a population. The
      individuals (i.e. a group of genomes within a collection) are defined by any kind
      of particular phenotypic or biological properties inside a related population
      (i.e. collection of genomes). The performance of the genetic markers is computed
      by a distance value which takes into account both sensitivity and specificity. In
      this study we report two examples of GTEvaluator application. In the first
      example Bacillus phenotypic markers were evaluated for their capacity to
      distinguish B. cereus from B. thuringiensis. In the second experiment,
      GTEvaluator measured the performance of genetic markers dedicated to the
      molecular serotyping of Salmonella enterica. In one in silico experiment it was
      possible to test 64 markers onto 134 genomes corresponding to 14 different
      serotypes.

PMID- 28750050
TI  - Staphylococcus aureus single-stranded DNA-binding protein SsbA can bind but
      cannot stimulate PriA helicase.
AB  - Single-stranded DNA-binding protein (SSB) and PriA helicase play important roles
      in bacterial DNA replication restart process. The mechanism by which PriA
      helicase is bound and stimulated by SSB in Escherichia coli (Ec) has been
      established, but information on this process in Gram-positive bacteria are
      limited. We characterized the properties of SSB from Staphylococcus aureus
      (SaSsbA, a counterpart of EcSSB) and analyzed its interaction with SaPriA. The
      gel filtration chromatography analysis of purified SaSsbA showed a stable
      tetramer in solution. The crystal structure of SaSsbA determined at 1.82 A
      resolution (PDB entry 5XGT) reveals that the classic
      oligonucleotide/oligosaccharide-binding folds are formed in the N-terminal DNA
      binding domain, but the entire C-terminal domain is disordered. Unlike EcSSB,
      which can stimulate EcPriA via a physical interaction between EcPriA and the C
      terminus of EcSSB (SSB-Ct), SaSsbA does not affect the activity of SaPriA. We
      also found that SaPriA can be bound by SaSsbA, but not by SaSsbA-Ct. Although no
      effect was found with SaSsbA, SaPriA can be significantly stimulated by the Gram
      negative Klebsiella pneumoniae SSB (KpSSB). In addition, we found that the
      conserved SSB-Ct binding site of KpPriA (Trp82, Tyr86, Lys370, Arg697, and
      Gln701) is not present in SaPriA. Arg697 in KpPriA is known to play a critical
      role in altering the SSB35/SSB65 distribution, but this corresponding residue in
      SaPriA is Glu767 instead, which has an opposite charge to Arg. SaPriA E767R
      mutant was constructed and analyzed; however, it still cannot be stimulated by
      SaSsbA. Finally, we found that the conserved MDFDDDIPF motif in the Gram-negative
      bacterial SSB is DISDDDLPF in SaSsbA, i.e., F172 in EcSSB and F168 in KpSSB is
      S161 in SaSsbA, not F. When acting with SaSsbA S161F mutant, the activity of
      SaPriA was dramatically enhanced elevenfold. Overall, the conserved binding
      sites, both in EcPriA and EcSSB, are not present in SaPriA and SaSsbA, thereby no
      stimulation occurs. Our observations through structure-sequence comparison and
      mutational analyses indicate that the case of EcPriA-EcSSB is not applicable to
      SaPriA-SaSsbA because of inherent differences among the species.

PMID- 28750051
TI  - Acute resistance exercise modulates microRNA expression profiles: Combined tissue
      and circulatory targeted analyses.
AB  - A subset of short non-coding RNAs, microRNAs (miRs), have been identified in the
      regulation of skeletal muscle hypertrophy and atrophy. Expressed within cells,
      miRs are also present in circulation (c-miR) and have a putative role in cross
      tissue signalling. The aim of this study was to examine the impact of a single
      bout of high intensity resistance exercise (RE) on skeletal muscle and
      circulatory miRs harvested simultaneously. Resistance trained males (n = 9, 24.6
      +/- 4.9 years) undertook a single bout of high volume RE with venous blood and
      muscle biopsies collected before, 2 and 4hr post-exercise. Real time polymerase
      chain reaction (Rt-PCR) analyses was performed on 30 miRs that have previously
      been shown to be required for skeletal muscle function. Of these, 6 miRs were
      significantly altered within muscle following exercise; miR-23a, -133a, -146a, 
      206, -378b and 486. Analysis of these same miRs in circulation demonstrated
      minimal alterations with exercise, although c-miR-133a (~4 fold, p = 0.049) and c
      miR-149 (~2.4 fold; p = 0.006) were increased 4hr post-exercise. Thus a single
      bout of RE results in the increased abundance of a subset of miRs within the
      skeletal muscle, which was not evident in plasma. The lack a qualitative
      agreement in the response pattern of intramuscular and circulating miR expression
      suggests the analysis of circulatory miRs is not reflective of the miR responses
      within skeletal muscle after exercise.

PMID- 28750052
TI  - Determinants of enrollment of informal sector workers in cooperative based health
      scheme in Bangladesh.
AB  - BACKGROUND: Providing access to affordable health care for the informal sector
      remains a considerable challenge for low income countries striving to make
      progress towards universal health coverage. The objective of the study is to
      identify the factors shaping the decision to enroll in a cooperative based health
      scheme for informal workers in Bangladesh and also help to identify the features
      of informal workers without health schemes and their likelihood of being insured.
      METHODS: Data were derived from a cross-sectional in-house survey within the
      catchment area of a cooperative based health scheme in Bangladesh during April
      June 2014, covering a total of 784 households (458 members and 326 non-members).
      Multivariate logistic regression model was used to identify factors associated
      with cooperative based health scheme and explanatory variables. FINDINGS: This
      study found that a number of factors were significant determinants of health
      scheme participation including sex of household head, household composition,
      occupational category as well as involvement social financial safety net
      programs. CONCLUSION: Findings from this study can be suggestive for policy
      makers interested in scaling up health insurance for informal workers in
      Bangladesh. Shared funding from this large informal sector can generate new
      resources for healthcare, which is in line with the healthcare financing strategy
      of Bangladesh as well as the recommendation of the World Health Organization for
      developing social health insurance as part of the path to Universal Health
      Coverage.

PMID- 28750053
TI  - Comprehensive structural analysis of designed incomplete polypeptide chains of
      the replicase nonstructural protein 1 from the severe acute respiratory syndrome
      coronavirus.
AB  - The cotranslational folding is recognized as a very cooperative process that
      occurs after the nearly completion of the polypeptide sequence of a domain. Here
      we investigated the challenges faced by polypeptide segments of a non-vectorial
      beta-barrel fold. Besides the biological interest behind the SARS coronavirus non
      structural protein 1 (nsp1, 117 amino acids), this study model has two structural
      features that motivated its use in this work: 1- its recombinant production is
      dependent on the temperature, with greater solubility when expressed at low
      temperatures. This is an indication of the cotranslational guidance to the native
      protein conformation. 2- Conversely, nsp1 has a six-stranded, mixed
      parallel/antiparallel beta-barrel with intricate long-range interactions,
      indicating it will need the full-length protein to fold properly. We used non
      denaturing purification conditions that allowed the characterization of
      polypeptide chains of different lengths, mimicking the landscape of the
      cotranslational fold of a beta-barrel, and avoiding the major technical
      hindrances of working with the nascent polypeptide bound to the ribosome. Our
      results showed partially folded states formed as soon as the amino acids of the
      second beta-strand were present (55 amino acids). These partially folded states
      are different based on the length of polypeptide chain. The native alpha-helix
      (amino acids 24-37) was identified as a transient structure (~20-30% propensity).
      We identified the presence of regular secondary structure after the fourth native
      beta-strand is present (89 amino acids), in parallel to the collapse to a non
      native 3D structure. Interestingly the polypeptide sequences of the native
      strands beta2, beta3 and beta4 have characteristics of alpha-helices. Our
      comprehensive analyses support the idea that incomplete polypeptide chains, such
      as the ones of nascent proteins much earlier than the end of the translation,
      adopt an abundance of specific transient folds, instead of disordered
      conformations.

PMID- 28750054
TI  - Assisted Design of Antibody and Protein Therapeutics (ADAPT).
AB  - Effective biologic therapeutics require binding affinities that are fine-tuned to
      their disease-related molecular target. The ADAPT (Assisted Design of Antibody
      and Protein Therapeutics) platform aids in the selection of mutants that
      improve/modulate the affinity of antibodies and other biologics. It uses a
      consensus z-score from three scoring functions and interleaves computational
      predictions with experimental validation, significantly enhancing the robustness
      of the design and selection of mutants. The platform was tested on three antibody
      Fab-antigen systems that spanned a wide range of initial binding affinities: bH1
      VEGF-A (44 nM), bH1-HER2 (3.6 nM) and Herceptin-HER2 (0.058 nM). Novel triple
      mutants were obtained that exhibited 104-, 46- and 32-fold improvements in
      binding affinity for each system, respectively. Moreover, for all three antibody
      antigen systems over 90% of all the intermediate single and double mutants that
      were designed and tested showed higher affinities than the parent sequence. The
      contributions of the individual mutants to the change in binding affinity appear
      to be roughly additive when combined to form double and triple mutants. The new
      interactions introduced by the affinity-enhancing mutants included long-range
      electrostatics as well as short-range nonpolar interactions. This diversity in
      the types of new interactions formed by the mutants was reflected in SPR kinetics
      that showed that the enhancements in affinities arose from increasing on-rates,
      decreasing off-rates or a combination of the two effects, depending on the
      mutation. ADAPT is a very focused search of sequence space and required only 20
      30 mutants for each system to be made and tested to achieve the affinity
      enhancements mentioned above.

PMID- 28750055
TI  - Longer sleep is associated with lower BMI and favorable metabolic profiles in UK
      adults: Findings from the National Diet and Nutrition Survey.
AB  - Ever more evidence associates short sleep with increased risk of metabolic
      diseases such as obesity, which may be related to a predisposition to non
      homeostatic eating. Few studies have concurrently determined associations between
      sleep duration and objective measures of metabolic health as well as sleep
      duration and diet, however. We therefore analyzed associations between sleep
      duration, diet and metabolic health markers in UK adults, assessing associations
      between sleep duration and 1) adiposity, 2) selected metabolic health markers and
      3) diet, using National Diet and Nutrition Survey data. Adults (n = 1,615, age 19
      65 years, 57.1% female) completed questions about sleep duration and 3 to 4 days
      of food diaries. Blood pressure and waist circumference were recorded. Fasting
      blood lipids, glucose, glycated haemoglobin (HbA1c), thyroid hormones, and high
      sensitivity C-reactive protein (CRP) were measured in a subset of participants.
      We used regression analyses to explore associations between sleep duration and
      outcomes. After adjustment for age, ethnicity, sex, smoking, and socioeconomic
      status, sleep duration was negatively associated with body mass index (-0.46
      kg/m2 per hour, 95% CI -0.69 to -0.24 kg/m2, p < 0.001) and waist circumference (
      0.9 cm per hour, 95% CI -1.5 to -0.3cm, p = 0.004), and positively associated
      with high-density lipoprotein cholesterol (0.03 mmol/L per hour, 95% CI 0.00 to
      0.05, p = 0.03). Sleep duration tended to be positively associated with free
      thyroxine levels and negatively associated with HbA1c and CRP (p = 0.09 to 0.10).
      Contrary to our hypothesis, sleep duration was not associated with any dietary
      measures (p >= 0.14). Together, our findings show that short-sleeping UK adults
      are more likely to have obesity, a disease with many comorbidities.

PMID- 28750056
TI  - Fatty-binding protein and galectin of Baylisascaris schroederi: Prokaryotic
      expression and preliminary evaluation of serodiagnostic potential.
AB  - Baylisascaris schroederi is a common parasite of captive giant pandas. The
      diagnosis of this ascariasis is normally carried out by a sedimentation
      floatation method or PCR to detect eggs in feces, but neither method is suitable
      for early diagnosis. Fatty acid-binding protein (FABP) and galectin (GAL) exist
      in various animals and participate in important biology of parasites. Because of
      their good immunogenicity, they are seen as potential antigens for the diagnosis
      of parasitic diseases. In this study, we cloned and expressed recombinant FABP
      and GAL from B. schroederi (rBs-FABP and rBs-GAL) and developed indirect enzyme
      linked immunosorbent assays (ELISAs) to evaluate their potential for diagnosing
      ascariasis in giant pandas. Immunolocalization showed that Bs-FABP and Bs-GAL
      were widely distributed in adult worms. The ELISA based on rBs-FABP showed
      sensitivity of 95.8% (23/24) and specificity of 100% (12/12), and that based on
      rBs-GAL had sensitivity of 91.7% (22/24) and specificity of 100% (12/12).

PMID- 28750057
TI  - Bactericidal activity of alpha-bromocinnamaldehyde against persisters in
      Escherichia coli.
AB  - Persisters are tolerant to multiple antibiotics, and widely distributed in
      bacteria, fungi, parasites, and even cancerous human cell populations, leading to
      recurrent infections and relapse after therapy. In this study, we investigated
      the potential of cinnamaldehyde and its derivatives to eradicate persisters in
      Escherichia coli. The results showed that 200 MUg/ml of alpha-bromocinnamaldehyde
      (Br-CA) was capable of killing all E. coli cells during the exponential phase.
      Considering the heterogeneous nature of persisters, multiple types of persisters
      were induced and exposed to Br-CA. Our results indicated that no cells in the
      ppGpp-overproducing strain or TisB-overexpressing strain survived the treatment
      of Br-CA although considerable amounts of persisters to ampicillin (Amp) and
      ciprofloxacin (Cip) were induced. Chemical induction by carbonyl cyanide m
      chlorophenylhydrazone (CCCP) led to the formation of more than 10% persister to
      Amp and Cip in the entire population, and Br-CA still completely eradicated them.
      In addition, the cells in the stationary phase, which are usually highly
      recalcitrant to antibiotics treatment, were also completely eradicated by 400
      MUg/ml of Br-CA. Further studies showed that neither thiourea (hydroxyl-radical
      scavenger) nor DPTA (Fe3+ chelator to block the hydroxyl-radical) affected the
      bactericidal efficiency of the Br-CA to kill E. coli, indicating a ROS
      independent bactericidal mechanism. Taken together, we concluded that Br-CA
      compound has a novel bactericidal mechanism and the potential to mitigate
      antibiotics resistance crisis.

PMID- 28750058
TI  - Human enteroviruses associated with and without diarrhea in Thailand between 2010
      and 2016.
AB  - Non-bacterial acute gastroenteritis (AGE) associated with virus infection affects
      individuals living in developing countries, especially children. To investigate
      whether shedding of certain human enterovirus (EV) is more frequently detected in
      the stool of individuals with AGE of unknown etiology than individuals without
      AGE symptoms, we tested fecal samples collected from 2,692 individuals with
      diarrhea between January 2010 and December 2016. Samples were tested for
      rotavirus, norovirus, and EV by reverse-transcription polymerase chain reaction
      (RT-PCR) and adenovirus by PCR. EV-positive samples were subjected to sequencing
      and phylogenetic analysis to identify EV species and types. Findings were
      compared to EV found in 1,310 fecal samples from individuals without AGE who were
      diagnosed with hand, foot, and mouth disease (HFMD). While the majority of
      viruses identified in AGE consisted of human rotavirus (22.7%), norovirus (11.4%)
      and adenovirus (9.3%), we identified EV (6.2%) belonging mainly to species B, C,
      and rhinovirus. In contrast, >92% of EV found without AGE symptoms belonged to
      species A. Although AGE symptoms are not often attributed to EV infection, EV was
      associated with diarrhea of unknown etiology at least in 3.4% of AGE cases. While
      CV-A6 was most likely to be found in stools of HFMD patients, rhinovirus A and C
      were the two most common EV species associated with AGE. Elucidating group
      specific EV infection in diseases with and without AGE will be useful in
      assisting identification, clinical management, and the surveillance of EV
      infection in the community.

PMID- 28750060
TI  - Correction: The New Face of the Old Molecules: Crustin Pm4 and Transglutaminase
      Type I Serving as RNPs Down-Regulate Astakine-Mediated Hematopoiesis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0072793.].

PMID- 28750059
TI  - High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure
      Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and
      transgender women.
AB  - Trials to assess microbicide safety require strict adherence to prescribed
      regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN
      017 was a phase 2, randomized sequence, open-label, expanded safety and
      acceptability crossover study comparing 1) daily oral emtricitabine/tenofovir
      disoproxil fumarate (FTC/TDF), 2) daily use of reduced-glycerin 1% tenofovir (RG
      TFV) gel applied rectally, and 3) RG-TFV gel applied before and after receptive
      anal intercourse (RAI)-if participants had no RAI in a week, they were asked to
      use two doses of gel within 24 hours. Product use was assessed by mixed methods
      including unused product return count, text messaging reports, and qualitative
      plasma TFV pharmacokinetic (PK) results. Convergence interviews engaged
      participants in determining the most accurate number of doses used based on
      product count and text messaging reports. Client-centered adherence counseling
      was also used. Participants (N = 187) were men who have sex with men and
      transgender women enrolled in the United States (42%), Thailand (29%), Peru (19%)
      and South Africa (10%). Mean age was 31.4 years (range 18-64 years). Based on
      convergence interviews, over an 8-week period, 94% of participants had >=80%
      adherence to daily tablet, 41% having perfect adherence; 83% had >=80% adherence
      to daily gel, 29% having perfect adherence; and 93% had >=80% adherence to twice
      weekly use during the RAI-associated gel regimen, 75% having perfect adherence
      and 77% having >=80% adherence to gel use before and after RAI. Only 4.4% of all
      daily product PK results were undetectable and unexpected (TFV concentrations
      <0.31 ng/mL) given self-reported product use near sampling date. The mixed
      methods adherence measurement indicated high adherence to product use in all
      three regimens. Adherence to RAI-associated rectal gel use was as high as
      adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be
      an alternative for individuals uninterested in daily oral PrEP.

PMID- 28750061
TI  - Endocrine and aggressive responses to competition are moderated by contest
      outcome, gender, individual versus team competition, and implicit motives.
AB  - This study examined hormonal responses to competition in relation to gender,
      social context, and implicit motives. Participants (N = 326) were randomly
      assigned to win or lose in a 10-round, virtual face-to-face competition, in same
      sex individual- and team-competition contexts. Saliva samples, taken before and
      twice after the competition, were assayed for testosterone (T), estradiol (E),
      progesterone (P), and cortisol (C). Implicit needs for power (nPower) and
      affiliation (nAffiliation) were assessed with a picture-story exercise before the
      competition. Aggression was measured via the volume at which participants set
      noise blasts for their opponents. Men competing individually and women competing
      as teams showed similar T increases after winning. C was differentially
      associated with outcome in the team matches, with higher post-match cortisol for
      winning women, and an opposite effect for male teams. Analyses including implicit
      motives indicated that situational variables interacted with motivational needs
      in shaping hormonal responses to competition: in naturally cycling women, nPower
      predicted T increases after winning and T and E decreases after losing. In men,
      nPower predicted T increases after losing and decreases after winning. In male
      teams, nPower predicted C increases after losing, but not after winning, whereas
      in individual competitions, nPower was a general negative predictor of C changes
      in women. nAffiliation predicted P increases for women competing as teams, and P
      decreases for women competing individually. Aggression was higher in men, losers,
      and teams than in women, winners, and individuals. High aggression was associated
      with high baseline C in women competing individually and with low baseline C and
      C decreases in women competing as teams and in men generally. Our findings
      suggest that while situational and gender factors play a role in hormonal
      responses to competition, they also depend on their interplay with motivational
      factors. They also suggest that while aggression is strongly affected by
      situational factors in the context of a competition, it has no direct association
      with motivational and hormonal correlates of dominance (nPower, T, E) and instead
      is associated with (mostly) low levels of C.

PMID- 28750062
TI  - The effect of mangiferin on skin: Penetration, permeation and inhibition of ECM
      enzymes.
AB  - Mangiferin (2-C-beta-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a
      polyphenol with strong antioxidant properties. Mangiferin is obtained from the
      mango tree (Mangifera indica L., Anacardiaceae). It has been proven that
      mangiferin exhibits many pharmacological activities. The aim of this study was to
      analyze the penetration of mangiferin into the human skin and through the skin.
      According to our knowledge, skin penetration and permeation studies of mangiferin
      have not been analyzed so far. Additionally, the influence of mangiferin on two
      Extracellular Matrix Enzymes (ECM): collagenase and elastase, was evaluated for
      the first time. It has been indicated that mangiferin is able to permeate the
      stratum corneum and penetrate into the epidermis and dermis in comparable
      amounts. For confirmation of the obtained results, fluorescence microscopy was
      successfully utilized. The analysis revealed the capability of mangiferin to
      reversibly inhibit elastase and collagenase activity. The mechanism of mangiferin
      interaction with both enzymes was estimated as a noncompetitive inhibition.

PMID- 28750063
TI  - The role of tumour suppressor PDCD4 in beta cell death in hypoxia.
AB  - OBJECTIVE: Hypoxia is known to induce pancreatic beta cell dysfunction and
      apoptosis. Changes in Programmed Cell Death Gene 4 (PDCD4) expression have
      previously been linked with beta cell neogenesis and function. Our aim was to
      investigate the effects of hypoxia on cell viability, PDCD4 expression and
      subcellular localisation. METHODS: MIN6 beta cells and ARIP ductal cells were
      exposed to 1% (hypoxia) or 21% O2 (normoxia) for 12 or 24 hours. MTT assay, HPI
      staining, scanning electron microscopy, western blotting and immunocytochemistry
      analyses were performed to determine the effect of hypoxia on cell viability,
      morphology and PDCD4 expression. RESULTS: 24 hour exposure to hypoxia resulted in
      ~70% loss of beta cell viability (P<0.001) compared to normoxia. Both HPI
      staining and SEM analysis demonstrated beta cell apoptosis and necrosis after 12
      hours exposure to hypoxia. ARIP cells also displayed hypoxia-induced apoptosis
      and altered surface morphology after 24 hours, but no significant growth
      difference (p>0.05) was observed between hypoxic and normoxic conditions.
      Significantly higher expression of PDCD4 was observed in both beta cells
      (P<0.001) and ductal (P<0.01) cells under hypoxic conditions compared to
      controls. PDCD4 expression was localised to the cytoplasm of both beta cells and
      ductal cells, with no observed effects of hypoxia, normoxia or serum free
      conditions on intracellular shuttling of PDCD4. CONCLUSION: These findings
      indicate that hypoxia-induced expression of PDCD4 is associated with increased
      beta cell death and suggests that PDCD4 may be an important factor in regulating
      beta cell survival during hypoxic stress.

PMID- 28750064
TI  - Modified human glucagon-like peptide-1 (GLP-1) produced in E. coli has a long
      acting therapeutic effect in type 2 diabetic mice.
AB  - Glucagon-like peptide 1 (GLP-1) is a very potent insulinotropic hormone secreted
      into the blood stream after eating. Thus, it has potential to be used in
      therapeutic treatment of diabetes. The half-life of GLP-1, however, is very short
      due to its rapid cleavage by dipeptidyl peptidase IV (DPP-IV). This presents a
      great challenge if it is to be used as a therapeutic drug. GLP-1, like many other
      small peptides, is commonly produced through chemical synthesis, but is limited
      by cost and product quantity. In order to overcome these problems, a sequence
      encoding a six codon-optimized tandem repeats of modified GLP-1 was constructed
      and expressed in the E. coli to produce a protease-resistant protein, 6*mGLP-1.
      The purified recombinant 6*mGLP-1, with a yield of approximately 20 mg/L, could
      be digested with trypsin to obtain single peptides. The single mGLP-1 peptides
      significantly stimulated the proliferation of a mouse pancreatic beta cell line,
      MIN6. The recombinant peptide also greatly improved the oral glucose tolerance
      test of mice, exerted a positive glucoregulatory effect, and most notably had a
      glucose lowering effect for as long as 16.7 hours in mice altered to create a
      type 2 diabetic condition and exerted a positive glucoregulatory effect in db/db
      mice. These results indicate that recombinant 6*mGLP-1 has great potential to be
      used as an effective and cost-efficient drug for the treatment of type 2
      diabetes.

PMID- 28750065
TI  - Biochemical characterization of a new nicotinamidase from an unclassified
      bacterium thriving in a geothermal water stream microbial mat community.
AB  - Nicotinamidases are amidohydrolases that convert nicotinamide into nicotinic
      acid, contributing to NAD+ homeostasis in most organisms. In order to increase
      the number of nicotinamidases described to date, this manuscript characterizes a
      nicotinamidase obtained from a metagenomic library fosmid clone (JFF054_F02)
      obtained from a geothermal water stream microbial mat community in a Japanese
      epithermal mine. The enzyme showed an optimum temperature of 90 degrees C, making
      it the first hyperthermophilic bacterial nicotinamidase to be characterized,
      since the phylogenetic analysis of this fosmid clone placed it in a clade of
      uncultured geothermal bacteria. The enzyme, named as UbNic, not only showed an
      alkaline optimum pH, but also a biphasic pH dependence of its kcat, with a
      maximum at pH 9.5-10.0. The two pKa values obtained were 4.2 and 8.6 for pKes1
      and pKes2, respectively. These results suggest a possible flexible catalytic
      mechanism for nicotinamidases, which reconciles the two previously proposed
      mechanisms. In addition, the enzyme showed a high catalytic efficiency, not only
      toward nicotinamide, but also toward other nicotinamide analogs. Its mutational
      analysis showed that a tryptophan (W83) is needed in one of the faces of the
      active site to maintain low Km values toward all the substrates tested.
      Furthermore, UbNic proved to contain a Fe2+ ion in its metal binding site, and
      was revealed to belong to a new nicotinamidase subgroup. All these
      characteristics, together with its high pH- and thermal stability, distinguish
      UbNic from previously described nicotinamidases, and suggest that a wide
      diversity of enzymes remains to be discovered in extreme environments.

PMID- 28750066
TI  - Cross-modulation of pathogen-specific pathways enhances malnutrition during
      enteric co-infection with Giardia lamblia and enteroaggregative Escherichia coli.
AB  - Diverse enteropathogen exposures associate with childhood malnutrition. To
      elucidate mechanistic pathways whereby enteric microbes interact during
      malnutrition, we used protein deficiency in mice to develop a new model of co
      enteropathogen enteropathy. Focusing on common enteropathogens in malnourished
      children, Giardia lamblia and enteroaggregative Escherichia coli (EAEC), we
      provide new insights into intersecting pathogen-specific mechanisms that enhance
      malnutrition. We show for the first time that during protein malnutrition, the
      intestinal microbiota permits persistent Giardia colonization and simultaneously
      contributes to growth impairment. Despite signals of intestinal injury, such as
      IL1alpha, Giardia-infected mice lack pro-inflammatory intestinal responses,
      similar to endemic pediatric Giardia infections. Rather, Giardia perturbs
      microbial host co-metabolites of proteolysis during growth impairment, whereas
      host nicotinamide utilization adaptations that correspond with growth recovery
      increase. EAEC promotes intestinal inflammation and markers of myeloid cell
      activation. During co-infection, intestinal inflammatory signaling and cellular
      recruitment responses to EAEC are preserved together with a Giardia-mediated
      diminishment in myeloid cell activation. Conversely, EAEC extinguishes markers of
      host energy expenditure regulatory responses to Giardia, as host metabolic
      adaptations appear exhausted. Integrating immunologic and metabolic profiles
      during co-pathogen infection and malnutrition, we develop a working mechanistic
      model of how cumulative diet-induced and pathogen-triggered microbial
      perturbations result in an increasingly wasted host.

PMID- 28750067
TI  - The dissemination of motivational interviewing in Swedish county councils:
      Results of a randomized controlled trial.
AB  - OBJECTIVE: A significant number of Swedish practitioners are offered workshop
      trainings in motivational interviewing through community-based implementation
      programs. The objective of this randomized controlled trial was to evaluate to
      what extent the practitioners acquire and retain skills from additional
      supervision consisting of feedback based on monitoring of practice. MATERIALS AND
      METHODS: A total of 174 practitioners in five county councils across Sweden were
      randomized to one of the study's two groups: 1) Regular county council workshop
      training, 2) Regular county council workshop training followed by six sessions of
      supervision. The participant's mean age was 43.3 years, and the majority were
      females (88.1%). RESULTS: Recruiting participants proved difficult, which may
      have led to a biased sample of practitioners highly motivated to learn the
      method. Although slightly different in form and content, all the workshop
      trainings increased the participants' skills to the same level. Also, consistent
      with previous research, the additional supervision group showed larger gains in
      proficiency compared to the group who received workshop training only at the six
      month follow-up. However, analyses showed generally maintained levels of skills
      for all the participants at the follow-up assessment, and the majority of
      participants did not attain beginning proficiency levels at either post-workshop
      or follow-up. CONCLUSIONS: The results of this study address the real-life
      implications of dissemination of evidence-based practices. The maintained level
      of elevated skills for all participants is a promising finding. However, the low
      interest for obtaining additional supervision among the Swedish practitioners is
      problematic. In addition, neither the workshop trainings nor the additional
      supervision, although improving skills, were sufficient for most of the
      participants to reach beginning proficiency levels. This raises questions
      regarding the most efficient form of training to attain and sustain adequate
      practice standards, and how to create incentive and interest among practitioners
      to participate in such training.

PMID- 28750068
TI  - Using actor-partner interdependence modeling to understand HPV vaccine
      acceptance.
AB  - A wealth of scientific literature has been devoted to understanding what factors
      influence parents and their adolescent children to obtain the HPV vaccine. This
      literature is relatively uniform in its methodological approach of sampling
      individuals (i.e., either parents or adolescents) and examining the predictors of
      uptake for that individual. To improve understanding of HPV vaccination uptake,
      we sampled low-income, African American parent-child dyads with either a female
      (n = 93) or a male (n = 116) adolescent who had not been vaccinated. Both parents
      and children completed self-report measures that tapped intent to receive the
      vaccine and hypothesized predictors of intent (i.e., self-efficacy, beliefs about
      the vaccine, beliefs about HPV, knowledge of HPV). Using a dyadic analytic
      approach (i.e., the Actor-Partner Interdependence Model or APIM) [1], we found
      that parents and their adolescents have different structures of beliefs regarding
      HPV vaccination (i.e., they are empirically distinguishable). Consistent with
      prior research, the majority of predictors of an individual's own intention to
      vaccinate were individual-level variables; uniquely though, some predictors
      endorsed by one member of the dyad influenced the intentions held by the other
      member. Specifically, parents' reports of HPV severity and their self-efficacy
      were both associated with adolescents' intent to obtain the vaccine. Further,
      adolescents' beliefs that the vaccine will lead to greater promiscuity or be
      stigmatizing were associated with parents holding an increased intent to
      vaccinate. Use APIM improves understanding of HPV vaccination uptake and can be
      used to guide intervention efforts.

PMID- 28750069
TI  - Does repeated pleural culture increase the diagnostic yield of Mycobacterium
      tuberculosis from tuberculous pleural effusion in HIV-negative individuals?
AB  - BACKGROUND: Despite recent advances in methods for culturing Mycobacterium
      tuberculosis (MTB), the diagnostic yield of tuberculous pleural effusion (TBPE)
      remains unsatisfactory. However, unlike repeated sputum cultures of pulmonary
      tuberculosis, little is known about the role of repeated pleural cultures. We
      examined whether repeated pleural cultures are associated with increased MTB
      yield from TBPE. METHODS: A multicenter, retrospective cohort study was performed
      from January 2012 to December 2015 in South Korea. Patients were categorized into
      two groups: single- or repeated-culture groups. The diagnostic yield of MTB and
      clinical, radiological, and pleural fluid characteristics were evaluated.
      RESULTS: Among the 329 patients with TBPE, 77 (23.4%) had repeated cultures and
      252 (76.5%) had a single culture. Pleural culture was performed twice in all 77
      patients in the repeated-culture group at a 1-day interval (inter-quartile range,
      1.0-2.0). In the repeated-culture group, the yield of MTB from the first culture
      was 31.2%, which was similar to that in the single-culture group (31.2% vs.
      29.8%, P = 0.887). However, the yield of MTB from the second culture (10/77,
      13.0%) was more than that from the first. These results may be attributable to
      the insufficient immune clearance for MTB invasion into the pleural space between
      the first and second cultures. Over time, the yield of the second cultures
      decreased from 17.4% to 6.7% and then 6.3%. Finally, the overall yield of MTB in
      the repeated- and single-culture groups was 44.2% and 29.8% respectively (P <
      0.001). CONCLUSIONS: The results showed that repeated pleural cultures increased
      MTB yield from TBPE in human immunodeficiency virus-negative individuals.
      Furthermore, repeated cultures may increase yield when carried out for two
      consecutive days.

PMID- 28750070
TI  - Low HIV incidence in pregnant and postpartum women receiving a community-based
      combination HIV prevention intervention in a high HIV incidence setting in South
      Africa.
AB  - BACKGROUND: Young Southern African women have the highest HIV incidence globally.
      Pregnancy doubles the risk of HIV acquisition further, and maternal HIV
      acquisition contributes significantly to the paediatric HIV burden. Little data
      on combination HIV prevention interventions during pregnancy and lactation are
      available. We measured HIV incidence amongst pregnant and postpartum women
      receiving a community-based combination HIV prevention intervention in a high HIV
      incidence setting in South Africa. METHODS: A cohort study that included HIV
      uninfected pregnant women was performed. Lay community-based workers provided
      individualized HIV prevention counselling and performed three-monthly home and
      clinic-based individual and couples HIV testing. Male partners were referred for
      circumcision, sexually transmitted infections or HIV treatment as appropriate.
      Kaplan-Meier analyses and Cox's regression were used to estimate HIV incidence
      and factors associated with HIV acquisition. RESULTS: The 1356 women included
      (median age 22.5 years) received 5289 HIV tests. Eleven new HIV infections were
      detected over 828.3 person-years (PY) of follow-up, with an HIV incidence rate of
      1.33 infections/100 PY (95% CI: 0.74-2.40). Antenatally, the HIV incidence rate
      was 1.49 infections/100 PY (95% CI: 0.64-2.93) and postnatally the HIV incidence
      rate was 1.03 infections/100 PY (95% CI: 0.33-3.19). 53% of male partners
      received HIV testing and 66% of eligible partners received referral for
      circumcision. Women within known serodiscordant couples, and women with newly
      diagnosed HIV-infected partners, adjusted hazard ratio (aHR) = 32.7 (95% CI: 3.8
      282.2) and aHR = 126.4 (95% CI: 33.8-472.2) had substantially increased HIV
      acquisition, respectively. Women with circumcised partners had a reduced risk of
      incident HIV infection, aHR = 0.22 (95% CI: 0.03-1.86). CONCLUSIONS: Maternal HIV
      incidence was substantially lower than previous regional studies. Community-based
      combination HIV prevention interventions may reduce high maternal HIV incidence
      in resource-poor settings. Expanded roll-out of home-based couples HIV testing
      and initiating pre-exposure prophylaxis for pregnant women within serodiscordant
      couples is needed in Southern Africa.

PMID- 28750072
TI  - The differences in crown formation during the splash on the thin water layers
      formed on the saturated soil surface and model surface.
AB  - Splash is the first stage of a negative phenomenon-soil erosion. The aim of this
      work was to describe the crown formation quantitatively (as part of the splash
      erosion) and compare the course of this phenomenon on the thin water film formed
      on a smooth glass surface and on the surface of saturated soil. The height of the
      falling water drop was 1.5 m. The observation of the crowns was carried out by
      high-speed cameras. The static and dynamic parameters of crown formation were
      analysed. It was found that the crowns formed on the water film covering the
      saturated soil surface were smaller and the time intervals of their existence
      were shorter. In addition, the shapes of the crowns were different from those
      created on the water layer covering the glass surface. These differences can be
      explained by the slightly different values of surface tension and viscosity of
      the soil solution, the greater roughness of the soil surface and the lower
      thickness of the water film on the soil surface.

PMID- 28750071
TI  - Rising tones and rustling noises: Metaphors in gestural depictions of sounds.
AB  - Communicating an auditory experience with words is a difficult task and, in
      consequence, people often rely on imitative non-verbal vocalizations and
      gestures. This work explored the combination of such vocalizations and gestures
      to communicate auditory sensations and representations elicited by non-vocal
      everyday sounds. Whereas our previous studies have analyzed vocal imitations, the
      present research focused on gestural depictions of sounds. To this end, two
      studies investigated the combination of gestures and non-verbal vocalizations. A
      first, observational study examined a set of vocal and gestural imitations of
      recordings of sounds representative of a typical everyday environment (ecological
      sounds) with manual annotations. A second, experimental study used non-ecological
      sounds whose parameters had been specifically designed to elicit the behaviors
      highlighted in the observational study, and used quantitative measures and
      inferential statistics. The results showed that these depicting gestures are
      based on systematic analogies between a referent sound, as interpreted by a
      receiver, and the visual aspects of the gestures: auditory-visual metaphors. The
      results also suggested a different role for vocalizations and gestures. Whereas
      the vocalizations reproduce all features of the referent sounds as faithfully as
      vocally possible, the gestures focus on one salient feature with metaphors based
      on auditory-visual correspondences. Both studies highlighted two metaphors
      consistently shared across participants: the spatial metaphor of pitch (mapping
      different pitches to different positions on the vertical dimension), and the
      rustling metaphor of random fluctuations (rapidly shaking of hands and fingers).
      We interpret these metaphors as the result of two kinds of representations
      elicited by sounds: auditory sensations (pitch and loudness) mapped to spatial
      position, and causal representations of the sound sources (e.g. rain drops,
      rustling leaves) pantomimed and embodied by the participants' gestures.

PMID- 28750073
TI  - A preliminary study to estimate contact rates between free-roaming domestic dogs
      using novel miniature cameras.
AB  - Information on contacts between individuals within a population is crucial to
      inform disease control strategies, via parameterisation of disease spread models.
      In this study we investigated the use of dog-borne video cameras-in conjunction
      with global positioning systems (GPS) loggers-to both characterise dog-to-dog
      contacts and to estimate contact rates. We customized miniaturised video cameras,
      enclosed within 3D-printed plastic cases, and attached these to nylon dog
      collars. Using two 3400 mAh NCR lithium Li-ion batteries, cameras could record a
      maximum of 22 hr of continuous video footage. Together with a GPS logger, collars
      were attached to six free roaming domestic dogs (FRDDs) in two remote Indigenous
      communities in northern Australia. We recorded a total of 97 hr of video footage,
      ranging from 4.5 to 22 hr (mean 19.1) per dog, and observed a wide range of
      social behaviours. The majority (69%) of all observed interactions between
      community dogs involved direct physical contact. Direct contact behaviours
      included sniffing, licking, mouthing and play fighting. No contacts appeared to
      be aggressive, however multiple teeth baring incidents were observed during play
      fights. We identified a total of 153 contacts-equating to 8 to 147 contacts per
      dog per 24 hr-from the videos of the five dogs with camera data that could be
      analysed. These contacts were attributed to 42 unique dogs (range 1 to 19 per
      video) which could be identified (based on colour patterns and markings). Most
      dog activity was observed in urban (houses and roads) environments, but contacts
      were more common in bushland and beach environments. A variety of foraging
      behaviours were observed, included scavenging through rubbish and rolling on dead
      animal carcasses. Identified food consumed included chicken, raw bones, animal
      carcasses, rubbish, grass and cheese. For characterising contacts between FRDD,
      several benefits of analysing videos compared to GPS fixes alone were identified
      in this study, including visualisation of the nature of the contact between two
      dogs; and inclusion of a greater number of dogs in the study (which do not need
      to be wearing video or GPS collars). Some limitations identified included
      visualisation of contacts only during daylight hours; the camera lens being
      obscured on occasion by the dog's mandible or the dog resting on the camera; an
      insufficiently wide viewing angle (36 degrees ); battery life and robustness of
      the deployments; high costs of the deployment; and analysis of large volumes of
      often unsteady video footage. This study demonstrates that dog-borne video
      cameras, are a feasible technology for estimating and characterising contacts
      between FRDDs. Modifying camera specifications and developing new analytical
      methods will improve applicability of this technology for monitoring FRDD
      populations, providing insights into dog-to-dog contacts and therefore how
      disease might spread within these populations.

PMID- 28750074
TI  - DPP4 gene variation affects GLP-1 secretion, insulin secretion, and glucose
      tolerance in humans with high body adiposity.
AB  - OBJECTIVE: Dipeptidyl-peptidase 4 (DPP-4) cleaves and inactivates the
      insulinotropic hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory
      polypeptide, collectively termed incretins. DPP-4 inhibitors entered clinical
      practice as approved therapeutics for type-2 diabetes in 2006. However, inter
      individual variance in the responsiveness to DPP-4 inhibitors was reported. Thus,
      we asked whether genetic variation in the DPP4 gene affects incretin levels,
      insulin secretion, and glucose tolerance in participants of the TUbingen Family
      study for type-2 diabetes (TUF). RESEARCH DESIGN AND METHODS: Fourteen common
      (minor allele frequencies >=0.05) DPP4 tagging single nucleotide polymorphisms
      (SNPs) were genotyped in 1,976 non-diabetic TUF participants characterized by
      oral glucose tolerance tests and bioimpedance measurements. In a subgroup of 168
      subjects, plasma incretin levels were determined. RESULTS: We identified a
      variant, i.e., SNP rs6741949, in intron 2 of the DPP4 gene that, after correction
      for multiple comparisons and appropriate adjustment, revealed a significant
      genotype-body fat interaction effect on glucose-stimulated plasma GLP-1 levels (p
      = 0.0021). Notably, no genotype-BMI interaction effects were detected (p = 0.8).
      After stratification for body fat content, the SNP negatively affected glucose
      stimulated GLP-1 levels (p = 0.0229), insulin secretion (p = 0.0061), and glucose
      tolerance (p = 0.0208) in subjects with high body fat content only. CONCLUSIONS:
      A common variant, i.e., SNP rs6741949, in the DPP4 gene interacts with body
      adiposity and negatively affects glucose-stimulated GLP-1 levels, insulin
      secretion, and glucose tolerance. Whether this SNP underlies the reported inter
      individual variance in responsiveness to DPP-4 inhibitors, at least in subjects
      with high body fat content, remains to be shown.

PMID- 28750075
TI  - CBirTox is a selective antigen-specific agonist of the Treg-IgA-microbiota
      homeostatic pathway.
AB  - Cultivating an environment of mutualism between host cells and the microbiota is
      vital, and dysregulation of this relationship is associated with multiple immune
      disorders including metabolic and skin diseases, asthma, allergy, and
      Inflammatory Bowel Disease (IBD). One prominent mechanism for maintaining
      homeostasis is the protective regulatory T cell (Treg)- Immunoglobulin A (IgA)
      pathway toward microbiota antigens, in which Tregs maintain homeostasis and
      provide critical survival factors to IgA+ B cells. In order to amplify the Treg
      IgA pathway, we have generated a fusion protein, CBirTox, comprised of a portion
      of the carboxy terminus of CBir1, a microbiota flagellin, genetically coupled to
      Cholera Toxin B subunit (CTB) via the A2 linker of CT. Both dendritic cells (DCs)
      and B cells pulsed with CBirTox selectively induced functional CD4+Foxp3+ Tregs
      in vitro, and CBirTox augmented CD4+Foxp3+ cell numbers in vivo. The induced
      Foxp3 expression was independent of retinoic acid (RA) signaling but was
      inhibited by neutralization of TGF-beta. CBirTox treatment of B cells
      downregulated mammalian target of rapamycin (mTOR) signaling. Furthermore,
      CBirTox-pulsed DCs induced substantial production of IgA from naive B cells.
      Collectively these data demonstrate that CBirTox represents a novel approach to
      bolstering the Treg-IgA pathway at the host-microbiota interface.

PMID- 28750076
TI  - Targeted next-generation sequencing detects novel gene-phenotype associations and
      expands the mutational spectrum in cardiomyopathies.
AB  - Cardiomyopathies are a heterogeneous group of primary diseases of the myocardium,
      including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and
      arrhythmogenic right ventricular cardiomyopathy (ARVC), with higher morbidity and
      mortality. These diseases are genetically diverse and associated with rare
      mutations in a large number of genes, many of which overlap among the phenotypes.
      To better investigate the genetic overlap between these three phenotypes and to
      identify new genotype-phenotype correlations, we designed a custom gene panel
      consisting of 115 genes known to be associated with cardiomyopathic phenotypes
      and channelopathies. A cohort of 38 unrelated patients, 16 affected by DCM, 14 by
      HCM and 8 by ARVC, was recruited for the study on the basis of more severe
      phenotypes and family history of cardiomyopathy and/or sudden death. We detected
      a total of 142 rare variants in 40 genes, and all patients were found to be
      carriers of at least one rare variant. Twenty-eight of the 142 rare variants were
      also predicted as potentially pathogenic variants and found in 26 patients. In 23
      out of 38 patients, we found at least one novel potential gene-phenotype
      association. In particular, we detected three variants in OBSCN gene in ARVC
      patients, four variants in ANK2 gene and two variants in DLG1, TRPM4, and AKAP9
      genes in DCM patients, two variants in PSEN2 gene and four variants in AKAP9 gene
      in HCM patients. Overall, our results confirmed that cardiomyopathic patients
      could carry multiple rare gene variants; in addition, our investigation of the
      genetic overlap among cardiomyopathies revealed new gene-phenotype associations.
      Furthermore, as our study confirms, data obtained using targeted next-generation
      sequencing could provide a remarkable contribution to the molecular diagnosis of
      cardiomyopathies, early identification of patients at risk for arrhythmia
      development, and better clinical management of cardiomyopathic patients.

PMID- 28750077
TI  - Understanding spearfishing in a coral reef fishery: Fishers' opportunities,
      constraints, and decision-making.
AB  - Social and ecological systems come together during the act of fishing. However,
      we often lack a deep understanding of the fishing process, despite its importance
      for understanding and managing fisheries. A quantitative, mechanistic
      understanding of the opportunities fishers encounter, the constraints they face,
      and how they make decisions within the context of opportunities and constraints
      will enhance the design of fisheries management strategies to meet linked
      ecological and social objectives and will improve scientific capacity to predict
      impacts of different strategies. We examined the case of spearfishing in a
      Caribbean coral reef fishery. We mounted cameras on fishers' spearguns to observe
      the fish they encountered, what limited their ability to catch fish, and how they
      made decisions about which fish to target. We observed spearfishers who dove with
      and without the assistance of compressed air, and compared the fishing process of
      each method using content analysis of videos and decision models of fishers'
      targeting selections. Compressor divers encountered more fish, took less time to
      catch each fish, and had a higher rate of successful pursuits. We also analyzed
      differences among taxa in this multispecies fishery, because some taxa are known
      to be ecologically or economically more valuable than others. Parrotfish are
      ecologically indispensable for healthy coral reefs, and they were encountered and
      captured more frequently than any other taxon. Fishers made decisions about which
      fish to target based on a fish's market value, proximity to the fisher, and
      taxon. The information uncovered on fishers' opportunities, constraints, and
      decision making has implications for managing this fishery and others. Moreover,
      it demonstrates the value of pursuing an improved understanding of the fishing
      process from the perspective of the fishers.

PMID- 28750078
TI  - Acridine orange fluorescent microscopy is more sensitive than India ink light
      microscopy in the rapid detection of cryptococcosis among CrAg positive HIV
      patients.
AB  - BACKGROUND: India ink microscopy on cerebrospinal fluid is still utilized in
      resource limited settings for the diagnosis of cryptococcal meningitis despite
      its poor sensitivity. We hypothesized that staining fungal nucleic acids with
      fluorescent dyes instead of the capsule with India ink might improve sensitivity
      for the diagnosis of cryptococcal meningitis. METHODS: We enrolled 96 HIV
      infected participants with cryptococcal meningitis who provided 194 CSF specimens
      at serial time points in Kampala, Uganda. Cryptococcosis was diagnosed by
      cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) test and only positive
      samples were included. We stained CSF with India ink and acridine orange. We
      cultured the same samples on standard fungal media. We compared acridine orange
      to CrAg, India ink and CSF culture. RESULTS: Acridine orange was more sensitive
      (96%) than India ink (79%) with reference to CSF CrAg. Acridine orange and India
      ink had a statistically significant difference (P<0.001) with a 25% correlation
      for detection of Cryptococcus yeasts. India ink had more negative results (22%)
      than acridine orange (4%). The sensitivity for India ink increased (86%) while
      that of acridine orange did not change (97%) when compared to CSF culture.
      However, both India ink and acridine orange had poor predictive values with
      reference to culture. CONCLUSION: Acridine orange is a better alternative to
      India ink in the rapid detection of cryptococcosis among CrAg positive HIV
      patients.

PMID- 28750079
TI  - Roles of the low density lipoprotein receptor and related receptors in inhibition
      of lipoprotein(a) internalization by proprotein convertase subtilisin/kexin type
      9.
AB  - Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are a causal risk factor
      for cardiovascular disease. The mechanisms underlying Lp(a) clearance from plasma
      remain unclear, which is an obvious barrier to the development of therapies to
      specifically lower levels of this lipoprotein. Recently, it has been documented
      that monoclonal antibody inhibitors of proprotein convertase subtilisin/kexin
      type 9 (PCSK9) can lower plasma Lp(a) levels by 30%. Since PCSK9 acts primarily
      through the low density lipoprotein receptor (LDLR), this result is in conflict
      with the prevailing view that the LDLR does not participate in Lp(a) clearance.
      To support our recent findings in HepG2 cells that the LDLR can act as a bona
      fide receptor for Lp(a) whose effects are sensitive to PCSK9, we undertook a
      series of Lp(a) internalization experiments using different hepatic cells, with
      different variants of PCSK9, and with different members of the LDLR family. We
      found that PCSK9 decreased Lp(a) and/or apo(a) internalization by Huh7 human
      hepatoma cells and by primary mouse and human hepatocytes. Overexpression of
      human LDLR appeared to enhance apo(a)/Lp(a) internalization in both types of
      primary cells. Importantly, internalization of Lp(a) by LDLR-deficient mouse
      hepatocytes was not affected by PCSK9, but the effect of PCSK9 was restored upon
      overexpression of human LDLR. In HepG2 cells, Lp(a) internalization was decreased
      by gain-of-function mutants of PCSK9 more than by wild-type PCSK9, and a loss-of
      function variant had a reduced ability to influence Lp(a) internalization. Apo(a)
      internalization by HepG2 cells was not affected by apo(a) isoform size. Finally,
      we showed that very low density lipoprotein receptor (VLDLR), LDR-related protein
      (LRP)-8, and LRP-1 do not play a role in Lp(a) internalization or the effect of
      PCSK9 on Lp(a) internalization. Our findings are consistent with the idea that
      PCSK9 inhibits Lp(a) clearance through the LDLR, but do not exclude other effects
      of PCSK9 such as on Lp(a) biosynthesis.

PMID- 28750080
TI  - Beliefs about hypertension among Nigerian immigrants to the United Kingdom: A
      qualitative study.
AB  - OBJECTIVE: The aim of the study was to elicit beliefs about hypertension among
      Nigerian immigrants in the United Kingdom. BACKGROUND: The distributions of
      cardiovascular risk factors and diseases are not shared equally across ethnic and
      economic groups in the United Kingdom. Its burden is more clustered among
      minority ethnic populations and migrant groups including black African Nigerian
      migrants. Similar patterns have been reported across Europe, Australia, Canada,
      Nordic countries and the United States of America. There are about 300 distinct
      ethnic groups in Nigeria and reliable information about their beliefs about
      hypertension is not available. Given that the United Kingdom has a large
      community of Nigerian immigrants from these different ethno-cultural backgrounds,
      understanding their unique beliefs about hypertension may help promote
      appropriate care for this population in the United Kingdom and Nigeria. SETTING:
      A single Pentecostal church community in West London. PARTICIPANTS: Twenty-seven
      Nigerian migrant members of the church entered and completed the study. METHODS
      AND OUTCOME MEASURE: A qualitative interview study was conducted. The interviews
      were analysed using thematic framework analysis. The outcome measures were
      emerging themes from the thematic framework analysis. RESULTS: Participants
      expressed beliefs in four major areas related to hypertension: (1) The Meaning of
      the term hypertension, (2) Perceptions of causation, (3) Effects of hypertension,
      and (4) Perceptions of treatment. The study revealed a diversity of beliefs about
      hypertension which incorporated both orthodox and culturally framed ideas.
      CONCLUSIONS: This study identified important beliefs among Nigerian migrants
      about hypertension that can contribute to our understanding of the management of
      hypertension in this group and suggests the need for further research to
      determine whether these beliefs may be representative of this group.

PMID- 28750081
TI  - Genome-wide analysis of basic/helix-loop-helix gene family in peanut and
      assessment of its roles in pod development.
AB  - The basic/helix-loop-helix (bHLH) proteins constitute a superfamily of
      transcription factors that are known to play a range of regulatory roles in
      eukaryotes. Over the past few decades, many bHLH family genes have been well
      characterized in model plants, such as Arabidopsis, rice and tomato. However, the
      bHLH protein family in peanuts has not yet been systematically identified and
      characterized. Here, 132 and 129 bHLH proteins were identified from two wild
      ancestral diploid subgenomes of cultivated tetraploid peanuts, Arachis duranensis
      (AA) and Arachis ipaensis (BB), respectively. Phylogenetic analysis indicated
      that these bHLHs could be classified into 19 subfamilies. Distribution mapping
      results showed that peanut bHLH genes were randomly and unevenly distributed
      within the 10 AA chromosomes and 10 BB chromosomes. In addition, 120 bHLH gene
      pairs between the AA-subgenome and BB-subgenome were found to be orthologous and
      101 of these pairs were highly syntenic in AA and BB chromosomes. Furthermore, we
      confirmed that 184 bHLH genes expressed in different tissues, 22 of which
      exhibited tissue-specific expression. Meanwhile, we identified 61 bHLH genes that
      may be potentially involved in peanut-specific subterranean. Our comprehensive
      genomic analysis provides a foundation for future functional dissection and
      understanding of the regulatory mechanisms of bHLH transcription factors in
      peanuts.

PMID- 28750082
TI  - Enhanced generation of iPSCs from older adult human cells by a synthetic five
      factor self-replicative RNA.
AB  - We previously devised a polycistronic, synthetic self-replicating RNA (srRNA) to
      generate human induced Pluripotent Stem Cells (iPSCs) that simultaneously
      expresses four reprogramming factors (4F). However, while the best 4F srRNA
      efficiently generated iPSCs from young fibroblasts, it was inefficient on adult
      human fibroblasts (>50 years). To increase the iPSC generation efficiency, we
      included additional reprogramming factors. We found that a single transfection of
      a five factor (5F) srRNA, containing OCT4, KLF4, SOX2, GLIS1 and c-MYC, robustly
      generated iPSCs from adult human fibroblasts aged 54 to 77 and from a 24 year old
      cardiomyopathy patient donor. Interestingly, 5F-srRNA induced LIN28A, which was
      one of the original reprogramming factors. 5F-srRNA also accelerated the
      generation of iPSCs by seven days compared to 4F-srRNAs. Further improvements
      include phosphatase treatment to remove 5' phosphate and use of Lipofectamine
      MessengerMAX that increased transfection efficiency to ~90%. Together, these
      improvements enabled us to efficiently generate iPSCs from human fibroblasts
      using 5F-srRNA while eliminating both puromycin selection and feeder cells.

PMID- 28750083
TI  - Health care workers' perceptions of point-of-care testing in a low-income country
      A qualitative study in Southwestern Uganda.
AB  - BACKGROUND: Point-of-care (POC) tests have become increasingly available and more
      widely used in recent years. They have been of particular importance to low
      income settings, enabling them with clinical capacities that had previously been
      limited. POC testing programs hold a great potential for significant improvement
      in low-income health systems. However, as most POC tests are developed in high
      income countries, disengagement between developers and end-users inhibit their
      full potential. This study explores perceptions of POC test end-users in a low
      income setting, aiming to support the development of novel POC tests for low
      income countries. METHODS: A qualitative study was conducted in Mbarara District,
      Southwestern Uganda, in October 2014. Fifty health care workers were included in
      seven focus groups, comprising midwives, laboratory technicians, clinical and
      medical officers, junior and senior nurses, and medical doctors. Discussions were
      audio-recorded and transcribed verbatim. Transcripts were coded through a data
      driven approach for qualitative content analysis. RESULTS: Nineteen different POC
      tests were identified as currently being in use. While participants displayed
      being widely accustomed to and appreciative of the use of POC tests, they also
      assessed the use and characteristics of current tests as imperfect. An ideal POC
      test was characterized as being adapted to local conditions, thoughtfully
      implemented in the specific health system, and capable of improving the care of
      patients. Tests for specific medical conditions were requested. Opinions differed
      with regard to the ideal distribution of POC tests in the local health system.
      CONCLUSION: POC tests are commonly used and greatly appreciated in this study
      setting. However, there are dissatisfactions with current POC tests and their
      use. To maximize benefit, stakeholders need to include end-user perspectives in
      the development and implementation of POC tests. Insights from this study will
      influence our ongoing efforts to develop POC tests that will be particularly
      usable in low-income settings.

PMID- 28750084
TI  - A computational modelling framework to quantify the effects of passaging cell
      lines.
AB  - In vitro cell culture is routinely used to grow and supply a sufficiently large
      number of cells for various types of cell biology experiments. Previous
      experimental studies report that cell characteristics evolve as the passage
      number increases, and various cell lines can behave differently at high passage
      numbers. To provide insight into the putative mechanisms that might give rise to
      these differences, we perform in silico experiments using a random walk model to
      mimic the in vitro cell culture process. Our results show that it is possible for
      the average proliferation rate to either increase or decrease as the passaging
      process takes place, and this is due to a competition between the initial
      heterogeneity and the degree to which passaging damages the cells. We also
      simulate a suite of scratch assays with cells from near-homogeneous and
      heterogeneous cell lines, at both high and low passage numbers. Although it is
      common in the literature to report experimental results without disclosing the
      passage number, our results show that we obtain significantly different closure
      rates when performing in silico scratch assays using cells with different passage
      numbers. Therefore, we suggest that the passage number should always be reported
      to ensure that the experiment is as reproducible as possible. Furthermore, our
      modelling also suggests some avenues for further experimental examination that
      could be used to validate or refine our simulation results.

PMID- 28750085
TI  - Orphan nuclear receptor ERRgamma is a key regulator of human fibrinogen gene
      expression.
AB  - Fibrinogen, 1 of 13 coagulation factors responsible for normal blood clotting, is
      synthesized by hepatocytes. Detailed roles of the orphan nuclear receptors
      regulating fibrinogen gene expression have not yet been fully elucidated. Here,
      we identified estrogen-related receptor gamma (ERRgamma) as a novel
      transcriptional regulator of human fibrinogen gene expression. Overexpression of
      ERRgamma specially increased fibrinogen expression in human hepatoma cell line.
      Cannabinoid receptor types 1(CB1R) agonist arachidonyl-2'-chloroethylamide (ACEA)
      up-regulated transcription of fibrinogen via induction of ERRgamma, whereas
      knockdown of ERRgamma attenuated fibrinogen expression. Deletion analyses of the
      fibrinogen gamma (FGG) gene promoter and ChIP assays revealed binding sites of
      ERRgamma on human fibrinogen gamma gene promoter. Moreover, overexpression of
      ERRgamma was sufficient to increase fibrinogen gene expression, whereas treatment
      with GSK5182, a selective inverse agonist of ERRgamma led to its attenuation in
      cell culture. Finally, fibrinogen and ERRgamma gene expression were elevated in
      liver tissue of obese patients suggesting a conservation of this mechanism.
      Overall, this study elucidates a molecular mechanism linking CB1R signaling,
      ERRgamma expression and fibrinogen gene transcription. GSK5182 may have
      therapeutic potential to treat hyperfibrinogenemia.

PMID- 28750086
TI  - Gene expression and metabolite profiling of gibberellin biosynthesis during
      induction of somatic embryogenesis in Medicago truncatula Gaertn.
AB  - Gibberellins (GAs) are involved in the regulation of numerous developmental
      processes in plants including zygotic embryogenesis, but their biosynthesis and
      role during somatic embryogenesis (SE) is mostly unknown. In this study we show
      that during three week- long induction phase, when cells of leaf explants from
      non-embryogenic genotype (M9) and embryogenic variant (M9-10a) were forming the
      callus, all the bioactive gibberellins from non-13-hydroxylation (GA4, GA7) and
      13-hydroxylation (GA1, GA5, GA3, GA6) pathways were present, but the contents of
      only a few of them differed between the tested lines. The GA53 and GA19
      substrates synthesized by the 13-hydroxylation pathway accumulated specifically
      in the M9-10a line after the first week of induction; subsequently, among the
      bioactive gibberellins detected, only the content of GA3 increased and appeared
      to be connected with acquisition of embryogenic competence. We fully annotated 20
      Medicago truncatula orthologous genes coding the enzymes which catalyze all the
      known reactions of gibberellin biosynthesis. Our results indicate that, within
      all the genes tested, expression of only three: MtCPS, MtGA3ox1 and MtGA3ox2, was
      specific to embryogenic explants and reflected the changes observed in GA53, GA19
      and GA3 contents. Moreover, by analyzing expression of MtBBM, SE marker gene, we
      confirmed the inhibitory effect of manipulation in GAs metabolism, applying
      exogenous GA3, which not only impaired the production of somatic embryos, but
      also significantly decreased expression of this gene.

PMID- 28750087
TI  - Risk prediction of developing venous thrombosis in combined oral contraceptive
      users.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a complex multifactorial disease
      influenced by genetic and environmental risk factors. An example for the latter
      is the regular use of combined oral contraceptives (CC), which increases the risk
      to develop VTE by 3 to 7 fold, depending on estrogen dosage and the type of
      progestin present in the pill. One out of 1'000 women using CC develops
      thrombosis, often with life-long consequences; a risk assessment is therefore
      necessary prior to such treatment. Currently known clinical risk factors
      associated with VTE development in general are routinely checked by medical
      doctors, however they are far from being sufficient for risk prediction, even
      when combined with genetic tests for Factor V Leiden and Factor II G20210A
      variants. Thus, clinical and notably genetic risk factors specific to the
      development of thrombosis associated with the use of CC in particular should be
      identified. METHODS AND FINDINGS: Step-wise (logistic) model selection was
      applied to a population of 1622 women using CC, half of whom (794) had developed
      a thromboembolic event while using contraceptives. 46 polymorphisms and clinical
      parameters were tested in the model selection and a specific combination of 4
      clinical risk factors and 9 polymorphisms were identified. Among the 9
      polymorphisms, there are two novel genetic polymorphisms (rs1799853 and
      rs4379368) that had not been previously associated with the development of
      thromboembolic event. This new prediction model outperforms (AUC 0.71, 95% CI
      0.69-0.74) previously published models for general thromboembolic events in a
      cross-validation setting. Further validation in independent populations should be
      envisaged. CONCLUSION: We identified two new genetic variants associated to VTE
      development, as well as a robust prediction model to assess the risk of
      thrombosis for women using combined oral contraceptives. This model outperforms
      current medical practice as well as previously published models and is the first
      model specific to CC use.

PMID- 28750088
TI  - A single nucleotide polymorphism causes enhanced radical oxygen species
      production by human aldehyde oxidase.
AB  - Aldehyde oxidases (AOXs) are molybdo-flavoenzymes characterized by broad
      substrate specificity, oxidizing aromatic/aliphatic aldehydes into the
      corresponding carboxylic acids and hydroxylating various heteroaromatic rings.
      The enzymes use oxygen as the terminal electron acceptor and produce reduced
      oxygen species during turnover. The physiological function of mammalian AOX
      isoenzymes is still unclear, however, human AOX (hAOX1) is an emerging enzyme in
      phase-I drug metabolism. Indeed, the number of xenobiotics acting as hAOX1
      substrates is increasing. Further, numerous single-nucleotide polymorphisms
      (SNPs) have been identified within the hAOX1 gene. SNPs are a major source of
      inter-individual variability in the human population, and SNP-based amino acid
      exchanges in hAOX1 reportedly modulate the catalytic function of the enzyme in
      either a positive or negative fashion. In this report we selected ten novel SNPs
      resulting in amino acid exchanges in proximity to the FAD site of hAOX1 and
      characterized the purified enzymes after heterologous expression in Escherichia
      coli. The hAOX1 variants were characterized carefully by quantitative differences
      in their ability to produce superoxide radical. ROS represent prominent key
      molecules in physiological and pathological conditions in the cell. Our data
      reveal significant alterations in superoxide anion production among the variants.
      In particular the SNP-based amino acid exchange L438V in proximity to the
      isoalloxanzine ring of the FAD cofactor resulted in increased rate of superoxide
      radical production of 75%. Considering the high toxicity of the superoxide in the
      cell, the hAOX1-L438V SNP variant is an eventual candidate for critical or
      pathological roles of this natural variant within the human population.

PMID- 28750089
TI  - A synthetic cationic antimicrobial peptide inhibits inflammatory response and the
      NLRP3 inflammasome by neutralizing LPS and ATP.
AB  - Antimicrobial peptides (AMPs) are one of the most important defense mechanisms
      against bacterial infections in insects, plants, non-mammalian vertebrates, and
      mammals. In the present study, a class of synthetic AMPs was evaluated for anti
      inflammatory activity. One cationic AMP, GW-A2, demonstrated the ability to
      inhibit the expression levels of nitric oxide (NO), inducible NO synthase (iNOS),
      cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha) and interleukin
      6 (IL-6) in lipopolysaccharide (LPS)-activated macrophages. GW-A2 reduced LPS
      induced increases in the phosphorylation of mitogen-activated protein kinase and
      protein kinase C-alpha/delta and the activation of NF-kappaB. GW-A2 also
      inhibited NLRP3 inflammasome activation induced by LPS and ATP. Furthermore, in
      the mice injected with LPS, GW-A2 reduced (1) the concentration of IL-1beta, IL-6
      and TNF-alpha in the serum; (2) the concentration of TNF-alpha in the peritoneal
      lavage; (3) the expression levels of iNOS, COX-2 and NLRP3 in the liver and lung;
      (4) the infiltration of polymorphonuclear neutrophils in the liver and lung. The
      underlying mechanisms for the anti-inflammatory activity of GW-A2 were found to
      be partially due to LPS and ATP neutralization. These results provide insights
      into how GW-A2 inhibits inflammation and the NLRP3 inflammasome and provide a
      foundation for the design of rational therapeutics for inflammation-related
      diseases.

PMID- 28750091
TI  - A testing-coverage software reliability model considering fault removal
      efficiency and error generation.
AB  - In this paper, we propose a software reliability model that considers not only
      error generation but also fault removal efficiency combined with testing coverage
      information based on a nonhomogeneous Poisson process (NHPP). During the past
      four decades, many software reliability growth models (SRGMs) based on NHPP have
      been proposed to estimate the software reliability measures, most of which have
      the same following agreements: 1) it is a common phenomenon that during the
      testing phase, the fault detection rate always changes; 2) as a result of
      imperfect debugging, fault removal has been related to a fault re-introduction
      rate. But there are few SRGMs in the literature that differentiate between fault
      detection and fault removal, i.e. they seldom consider the imperfect fault
      removal efficiency. But in practical software developing process, fault removal
      efficiency cannot always be perfect, i.e. the failures detected might not be
      removed completely and the original faults might still exist and new faults might
      be introduced meanwhile, which is referred to as imperfect debugging phenomenon.
      In this study, a model aiming to incorporate fault introduction rate, fault
      removal efficiency and testing coverage into software reliability evaluation is
      developed, using testing coverage to express the fault detection rate and using
      fault removal efficiency to consider the fault repair. We compare the performance
      of the proposed model with several existing NHPP SRGMs using three sets of real
      failure data based on five criteria. The results exhibit that the model can give
      a better fitting and predictive performance.

PMID- 28750090
TI  - Target specificity, in vivo pharmacokinetics, and efficacy of the putative STAT3
      inhibitor LY5 in osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma.
AB  - BACKGROUND: STAT3 is a transcription factor involved in cytokine and receptor
      kinase signal transduction that is aberrantly activated in a variety of sarcomas,
      promoting metastasis and chemotherapy resistance. The purpose of this work was to
      develop and test a novel putative STAT3 inhibitor, LY5. METHODS AND FINDINGS: An
      in silico fragment-based drug design strategy was used to create LY5, a small
      molecule inhibitor that blocks the STAT3 SH2 domain phosphotyrosine binding site,
      inhibiting homodimerization. LY5 was evaluated in vitro demonstrating good
      biologic activity against rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma cell
      lines at high nanomolar/low micromolar concentrations, as well as specific
      inhibition of STAT3 phosphorylation without effects on other STAT3 family
      members. LY5 exhibited excellent oral bioavailability in both mice and healthy
      dogs, and drug absorption was enhanced in the fasted state with tolerable dosing
      in mice at 40 mg/kg BID. However, RNAi-mediated knockdown of STAT3 did not
      phenocopy the biologic effects of LY5 in sarcoma cell lines. Moreover,
      concentrations needed to inhibit ex vivo metastasis growth using the PuMA assay
      were significantly higher than those needed to inhibit STAT3 phosphorylation in
      vitro. Lastly, LY5 treatment did not inhibit the growth of sarcoma xenografts or
      prevent pulmonary metastasis in mice. CONCLUSIONS: LY5 is a novel small molecule
      inhibitor that effectively inhibits STAT3 phosphorylation and cell proliferation
      at nanomolar concentrations. LY5 demonstrates good oral bioavailability in mice
      and dogs. However LY5 did not decrease tumor growth in xenograft mouse models and
      STAT3 knockdown did not induce concordant biologic effects. These data suggest
      that the anti-cancer effects of LY5 identified in vitro were not mediated through
      STAT3 inhibition.

PMID- 28750092
TI  - Cost-effectiveness of molecular point-of-care testing for influenza viruses in
      elderly patients at ambulatory care setting.
AB  - BACKGROUND: Early initiation of antiviral therapy in elderly patients with
      influenza is associated with reduced risk of extra clinic visit, hospitalization
      and death. This study examined the cost-effectiveness of molecular POCT for
      detection of influenza viruses in Hong Kong elderly patients with influenza-like
      illness (ILI) in the outpatient clinics. METHODS: A decision analytic model was
      used to simulate outcomes of a hypothetical cohort of elderly patients presented
      with ILI at outpatient clinics during peak season of influenza with two
      diagnostic approaches: Rapid molecular assay (POCT-PCR group) and clinical
      judgement with no POCT. Outcome measures included influenza-associated direct
      medical cost, hospitalization and mortality rates, quality-adjusted life year
      loss (QALY loss), and incremental cost per QALY saved (ICER). RESULTS: In base
      case analysis, POCT-PCR group was expected to reduce hospitalization (1.38%
      versus 2.85%) and mortality rate (0.08% versus 0.16%) and save 0.00112 QALYs at
      higher cost (by USD33.2 per ILI patient), comparing with clinical judgement
      group. The ICER of POCT-PCR was 29,582 USD/QALY saved. One-way sensitivity
      analyses found ICER sensitive to: Hospitalization rate without prompt antiviral
      therapy; odds ratio of hospitalization with prompt therapy; influenza prevalence;
      patient age and mortality rate of hospitalized patients. POCT-PCR was cost
      effective in 60.6% and 99.4% of 10,000 Monte Carlo simulations at willingness-to
      pay threshold of 1x and 3x gross domestic product per capita of Hong Kong,
      respectively. CONCLUSIONS: Molecular POCT for influenza detection in elderly
      patients with ILI at outpatient clinics during peak influenza season appeared to
      be cost-effective in Hong Kong.

PMID- 28750093
TI  - Correction: Optimal costs of HIV pre-exposure prophylaxis for men who have sex
      with men.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178170.].

PMID- 28750094
TI  - Crystal structure and kinetic analysis of the class B3 di-zinc metallo-beta
      lactamase LRA-12 from an Alaskan soil metagenome.
AB  - We analyzed the kinetic properties of the metagenomic class B3 beta-lactamase LRA
      12, and determined its crystallographic structure in order to compare it with
      prevalent metallo-beta-lactamases (MBLs) associated with clinical pathogens. We
      showed that LRA-12 confers extended-spectrum resistance on E. coli when expressed
      from recombinant clones, and the MIC values for carbapenems were similar to those
      observed in enterobacteria expressing plasmid-borne MBLs such as VIM, IMP or NDM.
      This was in agreement with the strong carbapenemase activity displayed by LRA-12,
      similar to GOB beta-lactamases. Among the chelating agents evaluated, dipicolinic
      acid inhibited the enzyme more strongly than EDTA, which required pre-incubation
      with the enzyme to achieve measurable inhibition. Structurally, LRA-12 contains
      the conserved main structural features of di-zinc class B beta-lactamases, and
      presents unique structural signatures that differentiate this enzyme from others
      within the family: (i) two loops (alpha3-beta7 and beta11-alpha5) that could
      influence antibiotic entrance and remodeling of the active site cavity; (ii) a
      voluminous catalytic cavity probably responsible for the high hydrolytic
      efficiency of the enzyme; (iii) the absence of disulfide bridges; (iv) a unique
      Gln116 at metal-binding site 1; (v) a methionine residue at position 221that
      replaces Cys/Ser found in other B3 beta-lactamases in a predominantly hydrophobic
      environment, likely playing a role in protein stability. The structure of LRA-12
      indicates that MBLs exist in wild microbial populations in extreme environments,
      or environments with low anthropic impact, and under the appropriate antibiotic
      selective pressure could be captured and disseminated to pathogens.

PMID- 28750095
TI  - Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: A
      systematic review and meta-analysis.
AB  - OBJECTIVE: We performed a comprehensive review and meta-analysis to evaluate the
      diagnostic values of serum single and multiplex tumor-associated autoantibodies
      (TAAbs) in patients with lung cancer (LC). METHODS: We searched the MEDLINE and
      EMBASE databases for relevant studies investigating serum TAAbs for the diagnosis
      of LC. The primary outcomes included sensitivity, specificity and accuracy of the
      test. RESULTS: The systematic review and meta-analysis included 31 articles with
      single autoantibody and 39 with multiplex autoantibodies. Enzyme-linked
      immunosorbent assay (ELISA) was the most common detection method. For the
      diagnosis of patients with all stages and early-stage LC, different single or
      combinations of TAAbs demonstrated different diagnostic values. Although
      individual TAAbs showed low diagnostic sensitivity, the combination of multiplex
      autoantibodies offered relatively high sensitivity. For the meta-analysis of a
      same panel of autoantibodies in patients at all stages of LC, the pooled results
      of the panel of 6 TAAbs (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1 and SOX2) were:
      sensitivity 38% (95% CI 0.35-0.40), specificity 89% (95% CI 0.86-0.91),
      diagnostic accuracy 65.9% (range 62.5-81.8%), AUC 0.52 (0.48-0.57), while the
      summary estimates of 7 TAAbs (p53, CAGE, NY-ESO-1, GBU4-5, SOX2, MAGE A4 and Hu
      D) were: sensitivity 47% (95% CI 0.34-0.60), specificity 90% (95% CI 0.89-0.92),
      diagnostic accuracy 78.4% (range 67.5-88.8%), AUC 0.90 (0.87-0.93). For the meta
      analysis of the same panel of autoantibodies in patients at early-stage of LC,
      the sensitivities of both panels of 7 TAAbs and 6 TAAbs were 40% and 29.7%, while
      their specificities were 91% and 87%, respectively. CONCLUSIONS: Serum single or
      combinations of multiplex autoantibodies can be used as a tool for the diagnosis
      of LC patients at all stages or early-stage, but the combination of multiplex
      autoantibodies shows a higher detection capacity; the diagnostic value of the
      panel of 7 TAAbs is higher than the panel of 6 TAAbs, which may be used as
      potential biomarkers for the early detection of LC.

PMID- 28750096
TI  - Correction: Lgl1 Is Required for Olfaction and Development of Olfactory Bulb in
      Mice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0162126.].

PMID- 28750097
TI  - Compensatory lung growth after bilobectomy in emphysematous rats.
AB  - Lung volume reduction surgery (LVRS) is an option for emphysematous patients who
      are awaiting lung transplantation. LVRS reduces nonfunctional portions of lung
      tissues and favors the compensatory lung growth (CLG) of the remaining lobes.
      This phenomenon diminishes dyspnea and improves both the respiratory mechanics
      and quality of life for the patients. An animal model of elastase-induced
      pulmonary emphysema was used to investigate the structural and functional lung
      response after LVRS. Bilobectomy was performed six weeks after elastase
      instillation. Two weeks after bilobectomy, CLG effects were evaluated by lung
      mechanics and histomorphometric analysis. After bilobectomy, the emphysematous
      animals presented decreased mean linear intercepts, increased elastic fiber
      proportion, and increased alveolar surface density, total volumes of airspace,
      tissue and respiratory region and absolute surface area. We conclude that
      bilobectomy promoted CLG in emphysematous animals, resulting in alveolar
      architecture repair.

PMID- 28750098
TI  - The unique N-terminal sequence of the BKCa channel alpha-subunit determines its
      modulation by beta-subunits.
AB  - Large conductance voltage- and Ca2+-activated K+ (BKCa) channels are essential
      regulators of membrane excitability in a wide variety of cells and tissues. An
      important mechanism of modulation of BKCa channel activity is its association
      with auxiliary subunits. In smooth muscle cells, the most predominant regulatory
      subunit of BKCa channels is the beta1-subunit. We have previously described that
      BKCa channels with distinctive N-terminal ends (starting with the amino acid
      sequence MDAL, MSSN or MANG) are differentially modulated by the beta1-subunit,
      but not by the beta2. Here we extended our studies to understand how the distinct
      N-terminal regions differentially modulate channel activity by beta-subunits. We
      recorded inside-out single-channel currents from HEK293T cells co-expressing the
      BKCa containing three N-terminal sequences with two beta1-beta2 chimeric
      constructs containing the extracellular loop of beta1 or beta2, and the
      transmembrane and cytoplasmic domains of beta2 or beta1, respectively. Both beta
      chimeric constructs induced leftward shifts of voltage-activation curves of
      channels starting with MANG and MDAL, in the presence of 10 or 100 MUM
      intracellular Ca2+. However, MSSN showed no shift of the voltage-activation, at
      the same Ca2+ concentrations. The presence of the extracellular loop of beta1 in
      the chimera resembled results seen with the full beta1 subunit, suggesting that
      the extracellular region of beta1 might be responsible for the lack of modulation
      observed in MSSN. We further studied a poly-serine stretch present in the N
      terminal region of MSSN and observed that the voltage-activation curves of BKCa
      channels either containing or lacking this poly-serine stretch were leftward
      shifted by beta1-subunit in a similar way. Overall, our results provide further
      insights into the mechanism of modulation of the different N-terminal regions of
      the BKCa channel by beta-subunits and highlight the extension of this region of
      the channel as a form of modulation of channel activity.

PMID- 28750099
TI  - Identification of RNA biomarkers for chemical safety screening in mouse embryonic
      stem cells using RNA deep sequencing analysis.
AB  - Although it is not yet possible to replace in vivo animal testing completely, the
      need for a more efficient method for toxicity testing, such as an in vitro cell
      based assay, has been widely acknowledged. Previous studies have focused on mRNAs
      as biomarkers; however, recent studies have revealed that non-coding RNAs
      (ncRNAs) are also efficient novel biomarkers for toxicity testing. Here, we used
      deep sequencing analysis (RNA-seq) to identify novel RNA biomarkers, including
      ncRNAs, that exhibited a substantial response to general chemical toxicity from
      nine chemicals, and to benzene toxicity specifically. The nine chemicals are
      listed in the Japan Pollutant Release and Transfer Register as class I designated
      chemical substances. We used undifferentiated mouse embryonic stem cells (mESCs)
      as a simplified cell-based toxicity assay. RNA-seq revealed that many mRNAs and
      ncRNAs responded substantially to the chemical compounds in mESCs. This finding
      indicates that ncRNAs can be used as novel RNA biomarkers for chemical safety
      screening.

PMID- 28750100
TI  - TGFBI functions similar to periostin but is uniquely dispensable during cardiac
      injury.
AB  - Extracellular matrix production and accumulation stabilize the heart under normal
      conditions as well as form a protective scar after myocardial infarction injury,
      although excessive extracellular matrix accumulation with long-standing heart
      disease is pathological. In the current study we investigate the role of the
      matricellular protein, transforming growth factor beta-induced (TGFBI), which is
      induced in various forms of heart disease. Additionally, we sought to understand
      whether TGFBI is functionally redundant to its closely related family member
      periostin, which is also induced in the diseased heart. Surgical models of
      myocardial infarction and cardiac pressure overload were used in mice with
      genetic loss of Postn and/or Tgfbi to examine the roles of these genes during the
      fibrotic response. Additionally, cardiac-specific TGFBI transgenic mice were
      generated and analyzed. We observed that deletion of Tgfbi did not alter cardiac
      disease after myocardial infarction in contrast to greater ventricular wall
      rupture in Postn gene-deleted mice. Moreover, Tgfbi and Postn double gene-deleted
      mice showed a similar post-myocardial infarction disease phenotype as Postn
      deleted mice. Over-expression of TGFBI in the hearts of mice had a similar effect
      as previously shown in mice with periostin over-expression. Thus, TGFBI and
      periostin act similarly in the heart in affecting fibrosis and disease
      responsiveness, although TGFBI is not seemingly necessary in the heart after
      myocardial infarction injury and is fully compensated by the more prominently
      expressed effector periostin.

PMID- 28750101
TI  - Helminth infection-induced malignancy.

PMID- 28750102
TI  - Stability of bacteriophages in burn wound care products.
AB  - Bacteriophages could be used along with burn wound care products to enhance
      antimicrobial pressure during treatment. However, some of the components of the
      topical antimicrobials that are traditionally used for the prevention and
      treatment of burn wound infection might affect the activity of phages. Therefore,
      it is imperative to determine the counteraction of therapeutic phage preparations
      by burn wound care products before application in patients. Five phages,
      representatives of two morphological families (Myoviridae and Podoviridae) and
      active against 3 common bacterial burn wound pathogens (Acinetobacter baumannii,
      Pseudomonas aeruginosa and Staphylococcus aureus) were tested against 13
      different products commonly used in the treatment of burn wounds. The
      inactivation of the phages was quite variable for different phages and different
      products. Majority of the anti-infective products affected phage activity
      negatively either immediately or in the course of time, although impact was not
      always significant. Products with high acidity had the most adverse effect on
      phages. Our findings demonstrate that during combined treatment the choice of
      phages and wound care products must be carefully defined in advance.

PMID- 28750103
TI  - Bacterial diversity in Buruli ulcer skin lesions: Challenges in the clinical
      microbiome analysis of a skin disease.
AB  - BACKGROUND: Buruli ulcer (BU) is an infectious disease caused by Mycobacterium
      ulcerans and considered the third most prevalent mycobacterial disease in humans.
      Secondary bacterial infections in open BU lesions are the main cause of pain,
      delayed healing and systemic illness, resulting in prolonged hospital stay. Thus,
      understanding the diversity of bacteria, termed the microbiome, in these open
      lesions is important for proper treatment. However, adequately studying the human
      microbiome in a clinical setting can prove difficult when investigating a
      neglected tropical skin disease due to its rarity and the setting.
      METHODOLOGY/PRINCIPAL FINDINGS: Using 16S rRNA sequencing, we determined the
      microbial composition of 5 BU lesions, 3 non-BU lesions and 3 healthy skin
      samples. Although no significant differences in diversity were found between BU
      and non-BU lesions, the former were characterized by an increase of Bacteroidetes
      compared to the non-BU wounds and the BU lesions also contained significantly
      more obligate anaerobes. With this molecular-based study, we were also able to
      detect bacteria that were missed by culture-based methods in previous BU studies.
      CONCLUSIONS/SIGNIFICANCE: Our study suggests that BU may lead to changes in the
      skin bacterial community within the lesions. However, in order to determine if
      such changes hold true across all BU cases and are either a cause or consequence
      of a specific wound environment, further microbiome studies are necessary. Such
      skin microbiome analysis requires large sample sizes and lesions from the same
      body site in many patients, both of which can be difficult for a rare disease.
      Our study proposes a pipeline for such studies and highlights several drawbacks
      that must be considered if microbiome analysis is to be utilized for neglected
      tropical diseases.

PMID- 28750104
TI  - BrEPS 2.0: Optimization of sequence pattern prediction for enzyme annotation.
AB  - The prediction of gene functions is crucial for a large number of different life
      science areas. Faster high throughput sequencing techniques generate more and
      larger datasets. The manual annotation by classical wet-lab experiments is not
      suitable for these large amounts of data. We showed earlier that the automatic
      sequence pattern-based BrEPS protocol, based on manually curated sequences, can
      be used for the prediction of enzymatic functions of genes. The growing sequence
      databases provide the opportunity for more reliable patterns, but are also a
      challenge for the implementation of automatic protocols. We reimplemented and
      optimized the BrEPS pattern generation to be applicable for larger datasets in an
      acceptable timescale. Primary improvement of the new BrEPS protocol is the
      enhanced data selection step. Manually curated annotations from Swiss-Prot are
      used as reliable source for function prediction of enzymes observed on protein
      level. The pool of sequences is extended by highly similar sequences from TrEMBL
      and SwissProt. This allows us to restrict the selection of Swiss-Prot entries,
      without losing the diversity of sequences needed to generate significant
      patterns. Additionally, a supporting pattern type was introduced by extending the
      patterns at semi-conserved positions with highly similar amino acids. Extended
      patterns have an increased complexity, increasing the chance to match more
      sequences, without losing the essential structural information of the pattern. To
      enhance the usability of the database, we introduced enzyme function prediction
      based on consensus EC numbers and IUBMB enzyme nomenclature. BrEPS is part of the
      Braunschweig Enzyme Database (BRENDA) and is available on a completely redesigned
      website and as download. The database can be downloaded and used with the
      BrEPScmd command line tool for large scale sequence analysis. The BrEPS website
      and downloads for the database creation tool, command line tool and database are
      freely accessible at http://breps.tu-bs.de.

PMID- 28750105
TI  - Additive Manufacturing Techniques in Prosthodontics: Where Do We Currently Stand?
      A Critical Review.
AB  - PURPOSE: The aim of this article was to critically review the current application
      of additive manufacturing (AM)/3D-printing techniques in prosthodontics and to
      highlight the influence of various technical factors involved in different AM
      technologies. MATERIALS AND METHODS: A standard approach of searching MEDLINE,
      EMBASE, and Google Scholar databases was followed. The following search terms
      were used: (Prosth* OR Restoration) AND (Prototype OR Additive Manufacture* OR
      Compute* OR 3D-print* OR CAD/CAM) AND (Dentistry OR Dental). Hand searching the
      reference lists of the included articles and personal connections revealed
      additional relevant articles. Selection criteria were any article written in
      English and reporting on the application of AM in prosthodontics from 1990 to
      February 2016. RESULTS: From a total of 4,290 articles identified, 33 were seen
      as relevant. Of these, 3 were narrative reviews, 18 were in vitro studies, and 12
      were clinical in vivo studies. Different AM technologies are applied in
      prosthodontics, directly and indirectly for the fabrication of fixed metal
      copings, metal frameworks for removable partial dentures, and plastic mock-ups
      and resin patterns for further conventional metal castings. Technical factors
      involved in different AM techniques influence the overall quality, the mechanical
      properties of the printed parts, and the total cost and manufacturing time.
      CONCLUSION: AM is promising and offers new possibilities in the field of
      prosthodontics, though its application is still limited. An understanding of
      these limitations and of developments in material science is crucial prior to
      considering AM as an acceptable method for the fabrication of dental prostheses.

PMID- 28750106
TI  - Diagnostic Classification and Design Considerations for Implant-Supported Fixed
      Partial Dentures and Screw Access Channel: The ABC/PBC and SAC Classifications.
AB  - Logical categorization of implant-supported fixed partial dentures (ISFPDs) based
      on implant angulation, abutment type, and screw access channel (SAC) design for
      screw-retained restoration is not available in the literature. This article
      proposes a simple classification system to describe implant angulations and
      prosthesis design affecting abutment selection (engaging or nonengaging) for
      ISFPDs. An additional classification that addresses screw access channel designs
      is also introduced. These classifications provide clear interpretation of
      clinical scenarios for ISFPD design consideration and a basis for categorization
      of future complications. The angulation-based and prosthetic-based
      classifications simplify communication regarding implant angulation and
      prosthesis design type for ISFPDs. The SAC classification assists in prosthetic
      design, factoring in function and esthetics when designing the screw access.

PMID- 28750107
TI  - Practice-Based Longitudinal Study of Multifactorial Risk Assessment for
      Periodontal Condition and Survival of Remaining Teeth in Patients with Removable
      Partial Dentures.
AB  - PURPOSE: This retrospective cohort study examined factors affecting the
      periodontal condition and survival of remaining teeth 5 years after removable
      partial denture (RPD) placement using multivariate analyses. MATERIALS AND
      METHODS: Of 231 patients who received RPDs at Tohoku University Hospital, 108
      patients who had agreed to undergo a 5-year follow-up were examined. The outcomes
      of RPD treatment were assigned to one of three categories: successful (n = 58),
      remake (n = 36), and failure (n = 14). A total of 80 patients in the successful
      and remake groups were included in this study. The parameters analyzed to
      evaluate the periodontal condition were probing depth, Miller index of tooth
      mobility, and bone resorption level. Criterion variables were the outcome of each
      periodontal condition, deterioration, and tooth loss. Independent variables were
      sex, age, smoking habit, number of periodic maintenance appointments, location of
      RPD, number of abutment teeth, denture base material, design, and existence of a
      denture in the opposite jaw. Bivariate analyses were performed using chi-square
      test, and multivariate regression analysis was used to assess significance.
      RESULTS: Sex and frequency of maintenance care were independently associated with
      deterioration of the periodontal condition. Sex and existence of a denture in the
      opposite jaw were independently associated with tooth loss. CONCLUSION: The
      findings suggest that periodic maintenance care and condition of the opposite jaw
      are essential for maintaining the condition of the remaining teeth.

PMID- 28750108
TI  - Occlusal Support and Temporomandibular Disorders Among Elderly Vietnamese.
AB  - PURPOSE: The aim of this study was to analyze the associations between missing
      teeth, occlusal support, and temporomandibular disorders (TMD) among elderly
      Vietnamese. MATERIALS AND METHODS: The study consisted of 145 TMD and 112 non-TMD
      (control group) participants aged 65 to 74 years. TMD was evaluated using
      Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I. An occlusal
      unit (OU) was defined as the cusp of a tooth coupled with the fossa of its
      antagonist tooth. A premolar pair was counted as one OU and a molar pair as two
      OUs. Dentition was divided into four occlusal support zones (OSZs) based on
      occluding pairs of posterior teeth by using Eichner classification: Class A had 4
      OSZs, Class B had 1 to 3 OSZs or only anterior teeth, and Class C had no OSZ.
      RESULTS: The TMD group lost significantly more posterior teeth (mean +/- SD 5.1
      +/- 4.7) than the control group (4.0 +/- 3.9, P = .033). The mean +/- SD OUs of
      the TMD and control groups were 5.1 +/- 4.6 and 6.0 +/- 4.3, respectively, which
      was nonsignificant (NS). The distribution of Class A (40.7%), Class B (40.0%),
      and Class C (19.3%) among the TMD group was not significantly different from the
      control group (50.0%, 38.4%, and 11.6%, respectively, NS). The odds of having TMD
      were positively associated with total unilateral loss of OUs (OR = 3.4, 95% CI =
      1.2-9.4, P = .020) and total bilateral loss of OUs (OR = 2.7, 95% CI = 1.2-6.6, P
      = .027). CONCLUSION: Total loss of OSZs on one or both sides of the mouth were
      found to be predictors of TMD among elderly Vietnamese.

PMID- 28750109
TI  - Comparison of Fixed Dental Prostheses with Zirconia and Metal Frameworks: Five
      Year Results of a Randomized Controlled Clinical Trial.
AB  - PURPOSE: The aim of this study was to test whether posterior zirconia-ceramic
      (ZC) and metal-ceramic (MC) fixed dental prostheses (FDPs) exhibit similar
      survival and technical/biologic complication rates. MATERIALS AND METHODS: A
      total of 58 patients in need of 76 posterior FDPs were randomly assigned to
      receive 40 ZC and 36 MC FDPs. The restorations were examined at baseline
      (cementation) and yearly for 5 years. Technical and biologic outcomes were
      compared. The independent treatment groups were compared with nonparametric Mann
      Whitney test for metric variables and with Fisher exact test for categoric data.
      RESULTS: A total of 52 patients with 40 ZC and 29 MC FDPs were examined at 5
      years. No FDP failed during the 5 years; 2 ZC FDPs failed at 65.4 and 73.3
      months. Debonding occurred at 3 ZC FDPs. Technical outcomes (modified US Public
      Health Service criteria) and general periodontal parameters did not show
      significant differences between ZC and MC FDPs. CONCLUSION: ZC FDPs exhibited
      similar outcomes to MC FDPs based on 5-year survival estimates. The majority of
      technical and biologic outcome measures were not significantly different.

PMID- 28750110
TI  - Challenges in International Comparison of Health Care Systems.

PMID- 28750111
TI  - Retinal Whitening After Uncomplicated Cataract Surgery.

PMID- 28750112
TI  - Febrile Neutropenia.

PMID- 28750113
TI  - Handheld Optical Coherence Tomography Angiography and Ultra-Wide-Field Optical
      Coherence Tomography in Retinopathy of Prematurity.
AB  - Importance: Retinopathy of prematurity (ROP) is a leading cause of childhood
      blindness worldwide. Optical coherence tomography (OCT) has improved the care of
      adults with vitreoretinal disease, and OCT angiography (OCTA) is demonstrating
      promise as a technique to visualize the retinal vasculature with lower risk and
      cost than fluorescein angiography. However, to date, there are no commercially
      available devices able to obtain ultra-wide-field OCT or OCTA images in neonates.
      Objective: To obtain ultra-wide-field OCT and OCTA images in neonates with ROP
      using a prototype handheld OCT and OCTA device. Design, Setting, and
      Participants: This observational case series was conducted from March 1 to April
      1, 2017, in an academic medical center among 4 neonates with ROP in the neonatal
      intensive care unit and in the operating room. Main Outcomes and Measures:
      Acquisition of wide-field OCT and OCTA images using a handheld prototype OCTA and
      ultra-wide-field OCT device. Results: Images were obtained from 4 neonates (1
      girl and 3 boys; mean age, 38 weeks' postmenstrual age [range, 34-43 weeks]) with
      various stages of ROP: 3 in the neonatal intensive care unit and 1 in the
      operating room. The system can obtain noncontact en face OCT images and
      horizontal line scans with an approximately 40 degrees  field of view and up to
      100 degrees  (ultra-wide-field) using a contact lens-based approach in a single 2
      second scan. In addition, 20 degrees  * 20 degrees  (approximately 4 * 4-mm) OCTA
      scans were obtained in patients with ROP in a single 2-second scan. Conclusions
      and Relevance: Optical coherence tomography and OCTA are gaining popularity in
      pediatric retinal imaging. This study reports on OCTA and ultra-wide-field OCT
      images in 4 neonates with various stages of ROP that were obtained using a
      prototype handheld device. Additional studies will be needed to prove the
      clinical value of this technology.

PMID- 28750114
TI  - Demonstrating Noninferiority of Accelerated Radiotherapy With Panitumumab vs
      Standard Radiotherapy With Cisplatin in Locoregionally Advanced Squamous Cell
      Head and Neck Carcinoma-Reply.

PMID- 28750116
TI  - Reported Complications Following Laser Vitreolysis.
AB  - Importance: Use of laser vitreolysis for symptomatic floaters has increased in
      recent years, but prospective studies are not available and the complication
      profile is poorly understood. Objective: To analyze cases of complications
      following laser vitreolysis as voluntarily reported to the American Society of
      Retina Specialists Research and Safety in Therapeutics (ASRS ReST) Committee, an
      independent task force formed to monitor device-related and drug-related safety
      events. Design, Setting, and Participants: A retrospective assessment was
      performed of all cases of complications following laser vitreolysis that were
      voluntarily reported by practitioners throughout the United States to the ASRS
      ReST Committee from the first report on September 19, 2016, through March 16,
      2017, the date of data analysis and manuscript writing. Main Outcomes and
      Measures: Complications reported to the ASRS ReST Committee following laser
      vitreolysis were analyzed by type to gain an understanding of the spectrum of
      potential complications. Results: A total of 16 complications following laser
      vitreolysis were reported in 15 patients by 7 US vitreoretinal specialists during
      the study period. Complications included elevated intraocular pressure leading to
      glaucoma; cataracts, including posterior capsule defects requiring cataract
      surgery; retinal tear; retinal detachment; retinal hemorrhages; scotomas; and an
      increased number of floaters. Conclusions and Relevance: This report presents a
      spectrum of complications reported to the ASRS ReST Committee across 6 months.
      The rate of complications cannot be determined because the denominator of total
      cases is unknown. Also, these findings cannot determine whether there is a causal
      association between these complications and laser vitreolysis. Prospective
      studies are warranted to better understand the efficacy of this procedure and the
      frequency of attendant complications. Until then, practitioners should be aware
      of the profile of potential complications to properly inform patients during the
      consent process. The ASRS ReST Committee will continue to monitor device-related
      and drug-related adverse events and encourages active surveillance and reporting
      by all physicians.

PMID- 28750117
TI  - Exercise-Induced Vertigo in Vestibular Schwannoma.

PMID- 28750115
TI  - Association of C-Reactive Protein Genetic Polymorphisms With Late Age-Related
      Macular Degeneration.
AB  - Importance: C-reactive protein (CRP) is a circulating inflammatory marker
      associated with late age-related macular degeneration (AMD). It remains uncertain
      whether the association between CRP concentrations and AMD is causal. Objective:
      To assess whether CRP (OMIM 123260) single-nucleotide polymorphisms that
      influence circulating CRP concentrations are associated with late AMD. Design,
      Setting, and Participants: Participants in 2 UK, hospital-based, case-control
      studies (Cambridge AMD study and Moorfields Eye Hospital AMD study) and 1 pan
      European, cross-sectional, population-based study (the European Eye [EUREYE]
      Study) were recruited between November 6, 2000, and April 30, 2007. Participants
      underwent dilated stereo-digital fundus photography graded according to the
      International Classification of Age-related Maculopathy and Macular Degeneration.
      There were 1727 cases of late AMD (1151 neovascular, 384 geographic atrophy, and
      192 mixed [neovascular AMD and geographic atrophy]) and 1153 controls. Early AMD
      cases (n = 574) were included only from the EUREYE Study. Data analysis was
      performed from August 1 to November 30, 2016. Four common single-nucleotide
      polymorphisms (rs1205, rs1130864, rs1800947, and rs3093077) were selected based
      on demonstrated influence on circulating CRP concentrations in the literature. In
      one study, genotyping of rs3093077 failed, and rs1800947 was typed in only 1
      study. Main Outcomes and Measures: A genetic multiplicative model was used for
      the association of single-nucleotide polymorphisms with late AMD adjusted for age
      and sex. Results: Among the 1727 patients with late AMD, the mean (SD) age was
      78.7 (7.4) years, and 668 (38.7%) were men. The mean (SD) age of the controls was
      74.9 (7.0) years, and 510 (44.2%) were men. In the pooled results of all 3
      studies, neither rs1205 (odds ratio [OR], 0.99; 95% CI, 0.86-1.14) nor rs1130864
      (OR, 0.96; 95% CI, 0.83-1.11) was associated with late AMD. For geographic
      atrophy, rs1205 had an OR of 0.91 (95% CI, 0.74-1.13) and rs1130864 had an OR of
      0.94 (95% CI, 0.76-1.16). For neovascular AMD, rs1205 had an OR of 1.01 (95% CI,
      0.87-1.19) and rs1130864 had an OR of 0.99 (95% CI, 0.84-1.16). There was no
      association of rs3093077 and rs1800947 with late AMD or any late AMD phenotype.
      There were no significant findings for early AMD. Conclusions and Relevance: Our
      results do not support a causal association between CRP concentrations and AMD.

PMID- 28750118
TI  - Modification of Chin Projection and Aesthetics With OnabotulinumtoxinA Injection.
AB  - Importance: Because of the soft-tissue envelope and the dimensional complexity of
      the muscular contraction of the mentalis muscle, the projection and shape of the
      chin is not determined by only the bony projection. In a subset of patients with
      a seemingly underprojected chin, a hyperactive, high-riding mentalis muscle
      contributes to a blunted chin contour. Objective: To evaluate the use of
      onabotulinumtoxinA (botulinum toxin A) for improving chin aesthetics in patients
      with an underprojected bony chin and a high-riding hyperactive mentalis muscle.
      Design, Setting, and Participants: This case series and photographic analysis
      included 11 patients presenting with an underprojected bony chin and a high
      riding hyperactive mentalis muscle at a private facial plastic surgery practice
      from August 25, 2006, to November 10, 2012. Data were analyzed from November 13,
      2012, to April 9, 2013. Interventions: Injection with 12 to 15 U of
      onabotulinumtoxinA into the mentalis muscle. Main Outcomes and Measures:
      Photographic analysis of the vertical and horizontal positions of the pogonion
      relative to fixed facial points before and after injection. A patient
      satisfaction scale was also used to assess improvement in overall chin aesthetic.
      Results: Eleven patients (3 men and 8 women; mean [SD] age, 46.3 [16.4] years)
      participated in the study, including 2 who had undergone prior chin implantation.
      The vertical position of the pogonion was more inferior after injection in 10 of
      11 patients (mean [SD] vertical position, 1.36 [0.18] preinjection and 1.44
      [0.18] postinjection; P = .005). Although the horizontal position of the pogonion
      changed in all patients, this change was not statistically significant (mean [SD]
      horizontal position, 0.11 [0.13] preinjection and 0.14 [0.13] postinjection; P =
      .32). All patients experienced improvement in their overall chin aesthetic and a
      subjective decrease in chin tension. Chin contour was improved, with soft-tissue
      volume overall displaced more inferiorly with a rounded rather than blunted
      appearance. No adverse effects were reported after injection. Conclusions and
      Relevance: OnabotulinumtoxinA is effective at improving chin aesthetics by
      altering the position of the pogonion. In this first photographic analysis to
      date of the influence of onabotulinumtoxinA treatment, patients demonstrated a
      measurable change in the position of the pogonion, in addition to improvements to
      the chin contour on profile. This nonsurgical mentoplasty may be used as an
      independent procedure or as an adjunct to optimize traditional chin augmentation
      in carefully selected patients. Level of Evidence: 4.

PMID- 28750119
TI  - Minimal Residual Disease in Chronic Lymphocytic Leukemia in the Era of Novel
      Agents: A Review.
AB  - Importance: The landscape of chronic lymphocytic leukemia (CLL) treatment has
      changed considerably since the first reported assessment of minimal residual
      disease (MRD) by flow cytometry in 1992. Chemoimmunotherapy (CIT) combinations
      have become the standard of care for most patients, and novel targeted agents are
      rapidly being incorporated into the front-line and relapsed settings. Minimal
      residual disease status has been shown to be a predictor of both progression-free
      survival (PFS) and overall survival (OS) at the time of response assessment
      following CIT, but less is known about the relationship between MRD and outcomes
      after novel oral therapeutics. Herein, we review current methods for MRD testing
      and present relevant clinical data for MRD for current treatment regimens
      focusing on novel oral agents as monotherapies and in combination. Observations:
      Flow cytometry and polymerase chain reaction are the 2 methods most frequently
      used to measure MRD, although high-throughput sequencing and more specific assays
      are being refined. Minimal residual disease status is an independent predictor of
      PFS and OS for patients receiving CIT, and emerging data for venetoclax suggest a
      relationship between MRD negativity and outcomes. The prognostic value of MRD
      status for kinase inhibitors remains unknown. Conclusions and Relevance: Minimal
      residual disease as a clinical trial end point must be validated in prospective
      studies prior to being used as a surrogate for survival. Given the heterogeneity
      of CLL biology and therapies, this validation must be regimen specific. Minimal
      residual disease assessments should be performed in clinical trial patients with
      both partial and complete responses. Following CIT, MRD status has prognostic
      value in all responders and this observation is important to validate with novel
      agents because most patients obtain partial remission. Further research is
      required to validate the use of MRD status as a decision point in guiding therapy
      in clinical practice.

PMID- 28750121
TI  - Erratum.

PMID- 28750120
TI  - Association Between Genomic Metrics and Immune Infiltration in Triple-Negative
      Breast Cancer.
AB  - Importance: Why some triple-negative breast cancers (TNBCs) have high and others
      have low immune cell infiltration is unknown. Understanding how immune
      surveillance shapes the cancer genome could help in the selection of patients and
      the development of more effective immunotherapy strategies. Objective: To examine
      the association between genomic metrics and the extent of immune infiltration in
      TNBCs. Design, Setting, and Participants: This study, performed from June 1,
      2015, through January 31, 2017, used DNA and RNA sequencing data and messenger
      RNA expression results from The Cancer Genome Atlas (TCGA) breast cancer data set
      (n = 1215) to calculate previously described immune metagene expression values
      and histologic lymphocyte counts to quantify immune infiltration and assign
      prognostic categories to TNBCs. It used the Molecular Taxonomy of Breast Cancer
      International Consortium (METABRIC) data set as an independent validation cohort.
      The study compared clonal heterogeneity, somatic total mutational load,
      neoantigen load, and somatic copy number alteration levels between immune-rich
      TNBC cohorts with good prognosis and immune-poor TNBC cohorts with poor
      prognosis. The study also compared the distribution of mutations in 119 canonical
      cancer genes. Main Outcomes and Measures: Correlation between immune prognostic
      category and genomic metrics of the cancer. Results: This study of 193 TNBC
      samples with patient survival information found an inverse association between
      clonal heterogeneity and immune metagene expression (rho = -0.395, P = 2 * 10-8).
      The study also found an inverse association between immune metagene expression
      and somatic copy number alteration levels (rho = -0.484, P = 2 * 10-10).
      Lymphocyte-rich TNBCs with good prognosis had significantly lower mutation and
      neoantigen counts than did lymphocyte-poor TNBCs with poor prognosis. The
      robustness of the study results was confirmed by using various immune metagenes
      in the same TCGA data set and in the independent METABRIC data set. Conclusions
      and Relevance: This study suggests that immune-rich TNBCs may be under an immune
      surveillance that continuously eliminates many immunogenic clones, resulting in
      lower clonal heterogeneity. These cancers may also represent the subset of TNBCs
      that could derive benefit from immune checkpoint inhibitor therapy to tilt the
      balance in favor of the immune system.

PMID- 28750122
TI  - Vision-Related Functional Burden of Diabetic Retinopathy Across Severity Levels
      in the United States.
AB  - Importance: Among adults with diabetes in the United States, severe forms of
      diabetic retinopathy (DR) are significantly associated with a greater vision
      related functional burden. Objective: To assess the functional burden of DR
      across severity levels in the United States. Design, Setting, and Participants:
      This cross-sectional study was based on 1004 participants 40 years or older with
      diabetes and valid ocular and sociodemographic outcomes in the National Health
      and Nutrition Examination Surveys (NHANES) (2005-2006 and 2007-2008). Diabetic
      retinopathy was based on fundus photograph grading, using the Early Treatment
      Diabetic Retinopathy Study severity scale. The analysis was performed from
      October 15, 2016, to June 15, 2017. Main Outcomes and Measures: Functional
      difficulties secondary to vision were assessed during a household questionnaire
      in which participants self-reported difficulty with reading, visuospatial tasks
      (ie, close-up work or finding things on a crowded shelf), mobility (ie, walking
      down steps, stairs, or curbs), and driving. The main outcome measure was vision
      related functional burden, which was defined as present for individuals reporting
      moderate or greater difficulty in any of the aforementioned tasks. Results: Of
      the 1004 persons with diabetes analyzed for this study (mean age, 65.7 years [95%
      CI, 64.0-67.3 years]; 51.1% male [95% CI, 47.1-55.2] and 48.9% female [95% CI,
      44.8-52.9]), the prevalence was 72.3% for no retinopathy, 25.4% for mild and
      moderate nonproliferative diabetic retinopathy (NPDR), and 2.3% for severe NPDR
      or proliferative diabetic retinopathy (PDR). The prevalence of vision-related
      functional burden was 20.2% (95% CI, 16.3%-24.1%) for those with no retinopathy,
      20.4% (95% CI, 15.3%-27.8%) for those with mild and moderate NPDR, and 48.5% (95%
      CI, 25.6%-71.5%) for those with severe NPDR or PDR (P = .02). In multivariable
      analysis, the odds of vision-related functional burden were significantly greater
      among those with severe NPDR or PDR relative to those with no retinopathy
      (adjusted odds ratio [aOR], 3.59; 95% CI, 1.29-10.05; P = .02). Those with severe
      NPDR or PDR did not have a statistically significant greater odds of vision
      related functional burden than did those with mild or moderate NPDR (aOR, 2.70;
      95% CI, 0.93-7.78; P = .07). Conclusions and Relevance: Among US adults with
      diabetes, approximately half of those with severe NPDR or PDR had difficulty with
      at least one visual function task. Moreover, vision-related functional burden was
      significantly greater among those with severe NPDR or PDR than among those with
      no retinopathy. These data suggest the importance of preventing severe forms of
      DR to mitigate the vision-related functional burden among US adults with
      diabetes. Future studies should complement our study by assessing the association
      of worsening retinopathy with objectively measured functional outcomes.

PMID- 28750124
TI  - Variations in the Prevalence of Hearing Loss in Children: Truth or Artifact?

PMID- 28750123
TI  - Prevalence of Hearing Loss in US Children and Adolescents: Findings From NHANES
      1988-2010.
AB  - Importance: There have been concerns about increasing levels of hearing
      impairment in children and adolescents, especially in relation to noise exposure,
      because even mild levels of hearing loss can affect educational outcomes.
      Objective: To further characterize changes in prevalence of hearing loss and
      noise exposures in the US pediatric population over time. Design, Setting, and
      Participants: This is a retrospective analysis of demographic and audiometric
      data from the Third National Health and Nutrition Examination Survey (NHANES III,
      1988-1994), NHANES 2005-2006, NHANES 2007-2008, and NHANES 2009-2010. The NHANES
      are nationally representative survey data sets collected and managed by the US
      National Center for Health Statistics, and this study includes a total of 7036
      survey participants ages 12 to 19 years with available audiometric measurements.
      Exposures: Hearing-related behaviors and risk factors such as history of ear
      infections, noise exposures, firearm use, and hearing protection use. Main
      Outcomes and Measures: Level of hearing loss measured by pure-tone audiometry, as
      well as high-frequency and low-frequency hearing loss and noise-induced threshold
      shifts. Results: Overall, data from 7036 survey participants ages 12 to 19 years
      with available audiometric measurements were analyzed. The prevalence of hearing
      loss increased from NHANES III to NHANES 2007-2008 (17.0% to 22.5% for >15 dB
      hearing loss; absolute difference, 5.5%; 95% CI, 6.1%-10.3%) but decreased in the
      NHANES 2009-2010 to 15.2% (absolute difference, 7.2%; 95% CI, 2.0%-12.4%) with no
      significant overall secular trend identified. There was an overall rise in
      exposure to loud noise or music through headphones 24 hours prior to audiometric
      testing from NHANES III to NHANES 2009-2010. However, noise exposure, either
      prolonged or recent, was not consistently associated with an increased risk of
      hearing loss across all surveys. The most recent survey cycle showed that
      nonwhite race/ethnicity and low socioeconomic status are independent risk factors
      for hearing loss. Conclusions and Relevance: This analysis did not identify
      significant changes in prevalence of hearing loss in US youth ages 12 to 19 years
      over this time period despite increases in reported noise exposures. No
      consistent associations were shown between noise exposure and hearing loss,
      though there was an association between racial/ethnic minority status and low
      socioeconomic status and increased risk of hearing loss. Ongoing monitoring of
      hearing loss in this population is necessary to elucidate long-term trends and
      identify targets for intervention.

PMID- 28750125
TI  - Demonstrating Noninferiority of Accelerated Radiotherapy With Panitumumab vs
      Standard Radiotherapy With Cisplatin in Locoregionally Advanced Squamous Cell
      Head and Neck Carcinoma.

PMID- 28750126
TI  - Association Between C-Reactive Protein and Age-Related Macular Degeneration: Les
      Liaisons Dangereuses.

PMID- 28750127
TI  - Health and Spirituality.

PMID- 28750128
TI  - The Impact and Influence of JAMA Facial Plastic Surgery: Showcasing Science and
      Relevance.

PMID- 28750129
TI  - Pemetrexed in Nonsquamous Non-Small-Cell Lung Cancer: The Billion Dollar Subgroup
      Analysis.

PMID- 28750130
TI  - Prevalence of Hearing Loss Among Children 9 to 11 Years Old: The Generation R
      Study.
AB  - Importance: Hearing loss (HL), a major cause of disability globally, negatively
      affects both personal and professional life. Objective: To describe the
      prevalence of sensorineural hearing loss (SNHL) among a population-based cohort
      of 9- to 11-year-old children, and to examine potential associations between
      purported risk factors and SNHL in early childhood. Design, Setting, and
      Participants: The study was among the general, nonclinical, pediatric community
      within the city of Rotterdam, the Netherlands, and was conducted between 2012 and
      2015 as a cross-sectional assessment within the Generation R Study, a population
      based longitudinal cohort study from fetal life until adulthood. Participants are
      children of included pregnant women in the Generation R Study with an expected
      delivery date between April 2002 and January 2006. They form a prenatally
      recruited birth cohort. Main Outcomes and Measures: Pure-tone air-conduction
      hearing thresholds were obtained at 0.5, 1, 2, 3, 4, 6, and 8 kHz, and
      tympanometry was performed in both ears. Demographic factors and parent-reported
      questionnaire data, including history of otitis media, were also measured.
      Results: A total of 5368 participants with a mean age of 9 years 9 months
      (interquartile range, 9 years 7 months-9 years 11 months) completed audiometry
      and were included in the analyses. A total of 2720 were girls (50.7%), and 3627
      (67.6%) were white. Most of the participants (4426 children [82.5%]) showed
      normal hearing thresholds 15 dB HL or less in both ears. Within the cohort, 418
      children (7.8%) were estimated to have SNHL (>=16 dB HL at low-frequency pure
      tone average; average at 0.5, 1, and 2 kHz or high-frequency pure-tone average;
      average at 3, 4, and 6 kHz in combination with a type A tympanogram) in at least
      1 ear, most often at higher frequencies. In multivariable analyses, a history of
      recurrent acute otitis media and lower maternal education were associated with
      the estimated SNHL at ages 9 to 11 years (odds ratio, 2.0 [95% CI. 1.5-2.8] and
      1.4 [95% CI, 1.1-1.7], respectively). Conclusions and Relevance: Within this
      cohort study in the Netherlands, 7.8% of the children ages 9 to 11 years had low
      frequency or high-frequency HL of at least 16 dB HL in 1 or both ears. A history
      of recurrent acute otitis media and lower maternal education seem to be
      independent risk factors for presumed SNHL in early childhood.

PMID- 28750131
TI  - Multispectral imaging system based on light-emitting diodes for the detection of
      melanomas and basal cell carcinomas: a pilot study (erratum).
AB  - This erratum corrects the error of an omitted author in doi:
      http://dx.doi.org/10.1117/1.JBO.22.6.065006

PMID- 28750132
TI  - Association of Skin Thickness With Alar Base Reduction in Patients Undergoing
      Lateral Crural Repositioning and Strut Grafting.
AB  - Importance: Knowing the operation plan is important for rhinoplasty surgeons to
      prevent unpredictable results. Objectives: To investigate the frequency of alar
      base resection in patients with different skin thickness who underwent lateral
      crural repositioning and lateral crural strut graft and to evaluate the results
      in the context of the current literature. Design, Setting, and Participants: This
      retrospective case series study included 621 patients who underwent primary open
      septorhinoplasty by the same surgeon between January 1, 2012, and June 30, 2015.
      From the surgical notes, operation type (lateral crural repositioning [LCrep]
      with lateral crural strut grafting [LCSG] and with or without alar base
      resection) and skin type were recorded. Study participants' skin types were
      determined intraoperatively and divided into 3 groups: (1) thick skin (the tip
      definition was limited by skin thickness and subcutaneous tissue), (2) thin skin
      (the tip cartilage was visible and could be observed despite overlying soft
      tissue and skin), and (3) normal skin (the tip cartilage during the procedure had
      no effect on the tip definition). Main Outcomes and Measures: The rate of alar
      base resection according to the type of operation performed and patient skin
      thickness. Results: Of the 621 patients in the study, 95 (15.3%) were men and 526
      (84.7%) were women. Lateral crural repositioning with LCSG was performed in 319
      surgical procedures (51.4%), and alar base reduction was performed in 329
      (53.0%). The rate of alar base resection differed significantly on the basis of
      whether LCrep with LCSG was performed (odds ratio [OR], 1.82; 95% CI, 1.32-2.50;
      P < .001). In patients with thin skin, there was no significant difference in the
      incidence of alar base resection associated with LCrep with LCSG (OR, 2.034; 95%
      CI, 0.912-4.539; P = .08). In patients with thick skin, a significant difference
      in the frequency of alar base resection was associated with the application of
      LCrep with LCSG (OR, 1.995; 95% CI, 1.228-3.241; P = .005). In patients with
      normal skin, LCrep with LCSG had no significant association with the frequency of
      alar base resection (OR, 1.557; 95% CI, 0.930-2.607; P = .09). Conclusions and
      Relevance: The necessity of alar base reduction after LCrep with LCSG is greater
      in patients with thick skin than in patients with thin and normal skin. This
      study is the first to our knowledge to examine this topic in rhinoplasty. Level
      of Evidence: 3.

PMID- 28750133
TI  - Role of Cytotoxic Tumor-Infiltrating Lymphocytes in Predicting Outcomes in
      Metastatic HER2-Positive Breast Cancer: A Secondary Analysis of a Randomized
      Clinical Trial.
AB  - Importance: Accumulating evidence indicates that tumor-infiltrating lymphocytes
      (TILs) are associated with clinical outcomes and may predict the efficacy of
      chemotherapy and human epidermal growth factor receptor 2 (HER2, encoded by the
      gene ERBB2)-targeted therapy in patients with HER2-positive breast cancer.
      Objective: To investigate the role of TILs, particularly cytotoxic CD8+ T cells,
      in the prediction of outcomes in patients with HER2-positive metastatic breast
      cancer randomized to an antibody-based (trastuzumab) vs a small molecule-based
      (lapatinib) anti-HER2 therapy. Design, Setting, and Participants: The Canadian
      Cancer Trials Group MA.31 phase 3 clinical trial accrued patients from 21
      countries and randomized 652 with HER2-positive metastatic breast cancer to
      receive trastuzumab or lapatinib, in combination with a taxane, from January 17,
      2008, through December 1, 2011. Patients had received no prior chemotherapy or
      HER2-targeted therapy in the metastatic setting. The median follow-up was 21.5
      months (interquartile range, 14.3-31.0). The tumor tissue collected for primary
      diagnosis was used in this ad hoc substudy. Sections were scored for TILs on
      hematoxylin-eosin (H&E)-stained sections, and immunohistochemical analysis was
      performed to assess CD8, FOXP3, CD56, and programmed cell death protein 1 (PD-1)
      expression on stromal (sTILs) and intratumoral TILs. Data were analyzed from July
      15, 2015, through July 27, 2016. Interventions: Treatment with trastuzumab or
      lapatinib in combination with taxane chemotherapy (paclitaxel or docetaxel) for
      24 weeks. Main Outcomes and Measures: Prognostic effects of biomarkers were
      evaluated for progression-free survival by stratified univariate log-rank test
      with Kaplan-Meier curves and by multivariate Cox proportional hazards regression;
      predictive effects were examined with a test of interaction between treatment
      allocation and biomarker classification. Results: Of the 647 treated women (mean
      [SD] age, 55.0 [10.8] years), 614 had tumor tissue samples scored for H&E sTILs
      and 427 for CD8 biomarker assessments. Overall H&E sTIL counts of greater than 5%
      (high) were present in 215 cases (35%) but did not show significant prognostic or
      predictive effects. Univariate stratified analyses detected a significant
      predictive effect on risk for progression with lapatinib compared with
      trastuzumab among patients with low CD8+ sTIL counts (observed hazard ratio,
      2.94; 95% CI, 1.40-6.17; P = .003) and among those with high CD8+ sTIL counts
      (observed hazard ratio, 1.36; 95% CI, 1.05-1.75; P = .02), confirmed in stepwise
      multivariate analysis (interaction P = .04). Other immunohistochemistry
      biomarkers were not associated with prognostic or predictive effects. Conclusions
      and Relevance: In this secondary analysis of a phase 3 randomized clinical trial,
      a low level of preexisting cytotoxic sTILs predicted the most benefit from an
      antibody- vs a small molecule-based drug against the same target. Trial
      Registration: clinicaltrials.gov Identifier: NCT00667251.

PMID- 28750134
TI  - Performance evaluation of a collapsed cone dose calculation algorithm for HDR Ir
      192 of APBI treatments.
AB  - PURPOSE: Most dose calculations for HDR brachytherapy treatments are based on the
      AAPM-TG43 formalism. Because patient's anatomy, heterogeneities, and applicator
      shielding are not considered, the dose calculation based on this formalism is
      inaccurate in some cases. Alternatively, collapsed cone (CC) methods as well as
      Monte Carlo (MC) algorithms belong to the model-based dose calculation
      algorithms, which are expected to improve the accuracy of calculated dose
      distributions. In this work, the performance of a CC algorithm, ACE in Oncentra
      Brachy 4.5 (ACE 4.5), has been investigated by comparing the calculated dose
      distributions to the AAPM-TG43 and MC calculations for 10 HDR brachytherapy
      accelerated partial breast irradiation treatments (APBI). Comparisons were also
      performed with a corrected version of ACE 4.5 (ACE 4.5/corr). METHODS: The
      brachytherapy source microSelectron mHDR-v2 (Elekta Brachytherapy) has been
      implemented in a MC environment and validated by comparing MC dose distributions
      simulated in a water phantom of 80 cm in diameter with dose distributions
      calculated with the AAPM-TG43 algorithm. Dose distributions calculated with ACE
      4.5, ACE 4.5/corr, AAPM-TG43 formalism, and MC for 10 APBI patients plans have
      then been computed and compared using HU scaled densities. In addition,
      individual dose components have been computed using ACE 4.5, ACE 4.5/corr, and
      MC, and compared individually. RESULTS: Local differences between MC and AAPM
      TG43 calculated dose distributions in a large water phantom are < 1%. When using
      HUs scaled densities for the breast cancer patients, both accuracy levels of ACE
      4.5 overestimate the MC calculated dose distributions for all analyzed dosimetric
      parameters. In the planning target volume (PTV), ACE 4.5 (ACE 4.5/corr)
      overestimates on average V100%,PTV by 3% +/- 1% (1% +/- 1%) and D50,PTV by 3% +/-
      1% (1% +/- 1%) and in the organs at risk D1cc, skin by 4% +/- 2% (1% +/- 1%),
      D0.5cc, ribs by 4% +/- 2% (0% +/- 1%), and D1cc, heart by 8% +/- 2% (3% +/- 1%)
      compared to MC. Comparisons of the individual dose components reveals an
      agreement for the primary component of < 2% local differences for both ACE 4.5
      and ACE 4.5/corr. Local differences of about 40% (20%) for the first and residual
      scatter components where observed when using ACE 4.5 (ACE 4.5/corr). Using
      uniform densities for one case shows a better agreement between ACE 4.5 and MC
      for all dosimetric parameters considered in this work. CONCLUSIONS: In general,
      on the 10 APBI patients the ACE 4.5/corr algorithm results in similar dose
      distributions as the commonly used AAPM-TG43 within the PTV. However, the
      accuracy of the ACE 4.5/corr calculated dose distribution is closer to MC than to
      AAPM-TG43. The differences between commercial version ACE 4.5 and MC dose
      distributions are mainly located in the first and residual scatter components. In
      ACE 4.5/corr, the changes done in the algorithm for the scatter components
      substantially reduce these differences.

PMID- 28750135
TI  - Ameliorative effect of chlorpromazine hydrochloride on visceral hypersensitivity
      in rats: possible involvement of 5-HT2A receptor.
AB  - BACKGROUND AND PURPOSE: Visceral hypersensitivity is responsible for pathogenesis
      of irritable bowel syndrome (IBS). Therefore, its prevention can help avoid
      abdominal pain and discomfort in IBS. To find candidate drugs for visceral
      hypersensitivity, we screened existing medicines for their ability to prevent
      visceral sensitivity induced by colorectal distension (CRD) in rats and
      identified chlorpromazine, a typical antipsychotic drug, as a candidate compound.
      In this study, we investigated the effect of chlorpromazine on visceral
      hypersensitivity. EXPERIMENTAL APPROACH: Visceral sensitivity (visceromotor
      response) was monitored by measuring the electrical activity of the abdominal
      external oblique muscle contraction in response to CRD using a barostat
      apparatus. Visceral hypersensitivity was induced by a colonic instillation of
      sodium butyrate or acetic acid in neonates. KEY RESULTS: Oral administration of
      chlorpromazine suppressed butyrate-induced visceral hypersensitivity to CRD.
      Interestingly, atypical antipsychotic drugs, quetiapine and risperidone,
      ameliorated butyrate-induced visceral hypersensitivity, whereas the typical
      antipsychotic drugs, haloperidol and sulpiride, did not. Pharmacological analysis
      using specific inhibitors showed that a selective 5-HT2A receptor antagonist,
      ketanserin, suppressed butyrate-induced visceral hypersensitivity, whereas a
      selective dopamine D2 receptor antagonist, L-741626, did not. Furthermore, the 5
      HT2A receptor agonist AL-34662 stimulated visceral sensitivity to CRD in healthy
      control rats but not in butyrate-treated rats. These findings suggest that
      increased 5-HT levels in the colon contribute to the induction of visceral
      hypersensitivity. CONCLUSIONS AND IMPLICATIONS: Our results indicate that
      chlorpromazine ameliorates visceral hypersensitivity and that the 5-HT2A receptor
      is a potential therapeutic target for treating abdominal pain and discomfort in
      IBS.

PMID- 28750136
TI  - Changes in margin re-excision rates: Experience incorporating the "no ink on
      tumor" guideline into practice.
AB  - INTRODUCTION: Prior to the "no ink on tumor" SSO/ASTRO consensus guideline,
      approximately 20% of women with stage I/II breast cancers undergoing breast
      conservation surgery at our institution underwent margin re-excision. On May 20,
      2013, our institution changed the definition of negative margins from 2 mm to "no
      ink on tumor." METHODS: A retrospective review was conducted of patients who had
      surgery at our institution with clinical stage I/II breast cancers between June
      1, 2011 and May 1, 2015. In the pre-guideline cohort (pre) and post-guideline
      cohort (post), negative margins were 2 mm and "no ink on tumor," respectively.
      RESULTS: Implementation of the guideline resulted in a significant decrease in
      the positive/close margin rate (29.6% pre vs 10.1% post; P < 0.001) and numerical
      decrease in re-excision rate (20.4% pre vs 16.3% post; P = 0.104). No significant
      difference was found in local recurrence between the cohorts with limited follow
      up (1.2% pre vs 1.5% post; P = 0.787). CONCLUSION: The implementation of the "no
      ink on tumor" guideline at our institution has resulted in a significant decrease
      in positive margin rates and a numerical decrease in margin re-excisions. In
      addition to margin status, surgeons continue to use individual patient and
      histologic factors to decide for or against margin re-excision.

PMID- 28750137
TI  - Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross-Reactive Nonsteroidal
      Anti-inflammatory Drug Hypersensitivity.
AB  - Our aim was to evaluate genetic polymorphism of molecules involved in
      immunoregulatory/allergic processes in patients who presented with cutaneous
      hypersensitivity caused by chemically unrelated nonsteroidal anti-inflammatory
      drugs. Polymorphisms at IL10 (-1082 G>A), IL4 (-589 C>T), CTLA4 (+49A>G), and DAO
      (+8956 C>G) genes were studied in 55 cases and 97 controls by the polymerase
      chain reaction-restriction fragment length polymorphism technique. With regard to
      the polymorphism at IL10 -1082, higher frequencies of the AG genotype (57% vs
      39%) and G allele carriers (70% vs 48%) were found among the patients, indicating
      a risk effect (odds ratio [OR] = 2.56 and P = .01 for AG genotype and OR = 2.52;
      P = .01 for AG/GG). For the CTLA4 +49 A/G single-nucleotide polymorphism (SNP),
      AG genotype (31.0%) (P = .02) and G carrier (54.0%) (P = .05) frequencies were
      found to be significantly lower in the patient group compared with the control
      group (51.0% and 69.0%, respectively). The SNP DAO +8956 C>G was associated with
      a strong protective effect, with OR values of 0.83 for CG and 0.11 for GG
      genotype (P = .04 for the codominant model), suggesting an allele dose effect.
      The combination of IL10 and DAO SNPs in a multivariate model did not alter the OR
      values, suggesting independent effects for both SNPs. The results are striking.
      In conclusion, these results suggest that polymorphisms in regulatory targets of
      the immune response and in DAO gene could modulate an individual's susceptibility
      to nonsteroidal anti-inflammatory drug hypersensitivity reactions. Further
      studies will be necessary to complement our results.

PMID- 28750138
TI  - Current approach of skin lesions suspected of malignancy in general practice in
      the Netherlands: a quantitative overview.
AB  - BACKGROUND: The role of general practitioners (GPs) in skin cancer care is
      increasing. Previous, hospital-based studies suggest that GPs might not have the
      capabilities to gain responsibility concerning skin cancer care. OBJECTIVES: To
      evaluate the current approach of GPs towards skin lesions suspected of malignancy
      in the Netherlands. METHODS: In three general practices, all consultations in
      2015 concerning skin lesions suspected of malignancy were identified and
      reviewed. Patients demographics, circumstances of consultation, evaluation of
      skin lesion(s), presumed diagnosis, diagnostic accuracy and policy were
      evaluated. RESULTS: Five hundred and eighty consultations were identified.
      Patient took initiative for encounter in 90%. Case-finding occurred in 2%.
      Diagnostic tools were used in 22%; dermoscopy was used in 8% and a diagnostic
      excision in 10%. The GP diagnosed a benign lesion in 69%. Therapeutic
      interventions were applied in 31% and a wait-and-see policy in 40%. The diagnosis
      after referral was a benign tumour in 39% of the cases, a malignancy in 29% and a
      premalignant lesion in 17%. The positive predictive value (PPV) of the presumed
      benign, malignant and premalignant diagnoses was 86%, 54% and 18%, respectively.
      CONCLUSIONS: Most lesions that are presented to the GP with a suspicion of a
      malignancy appear to be benign lesions. In the examined practices, the diagnosis
      of the GP is mainly based on clinical examination and little use is made of
      available diagnostic tools. The use of a diagnostic tool like a biopsy might
      prevent unnecessary referrals.

PMID- 28750139
TI  - Is mitotic rate still useful in the management of patients with thin melanoma?
AB  - BACKGROUND: T1 melanoma substaging was recently modified by the American Joint
      Committee on Cancer (AJCC). Although sentinel lymph node (SLN) positivity is the
      most important prognostic factor in melanoma, there is a lack of consensus on
      whether SLN biopsy should be performed in patients with thin melanoma (<=1 mm).
      OBJECTIVE: The main aim of this study was to investigate predictors of SLN
      positivity in patients with thin melanoma, with a special emphasis on mitotic
      rate. A secondary aim was to evaluate survival in this group of patients.
      MATERIALS AND METHODS: Retrospective multicenter observational study with
      analysis of age, sex, tumour location, thickness, mitotic rate, regression and
      microscopic satellites. Predictive factors were identified using a classification
      and regression tree (CART) approach. Melanoma-specific survival according to SLN
      status was estimated using Kaplan-Meier curves. RESULTS: We analysed 203 patients
      with a melanoma <=1 mm. Using the new AJCC staging criteria, the CART algorithm
      identified a 7.5% likelihood of SLN positivity in T1a patients. In the case of
      T1b melanoma, there was a 14.3% likelihood of SLN positivity in patients with a
      mitotic rate >1 mitosis/mm2 and a 3.2% likelihood in those with <=1 mitoses/mm2 .
      None of the patients with T1b disease who had <=1 mitoses/mm2 and regression had
      SLN positivity. In T1b patients, 5-year melanoma-specific survival was 98.7% in
      the SLN-negative group and 75% in the SLN-positive group (P = 0.05). When
      stratified by mitotic rate, survival was 100% for patients with a mitotic rate of
      <=1 mitoses/mm2 and 91.4% for those with >1 mitosis/mm2 (P = 0.022). There were
      no deaths in the T1a subgroup. CONCLUSIONS: Sentinel lymph node metastasis was
      less common in patients with T1b melanoma who had a mitotic rate of <=1
      mitoses/mm2 . Performance of SLN biopsy should be carefully considered in this
      subgroup of patients, particularly considering the good prognosis.

PMID- 28750140
TI  - The diagnosis and management of male genital lichen sclerosus: a retrospective
      review of 301 patients.
AB  - INTRODUCTION: Male genital lichen sclerosus (MGLSc) is an acquired, chronic,
      inflammatory skin disease that is associated with significant morbidity and
      squamous cell carcinoma of the penis (PSCC). However, some clinical, diagnostic
      and management controversies endure, including the relationship with penile
      intraepithelial neoplasia (PeIN). OBJECTIVES: To clarify clinical presentations,
      diagnostic approaches, histological findings, response to treatment and the
      relationship with PeIN. METHODS: Retrospective review of patients with a
      diagnosis of MGLSc who attended a specialist male genital dermatoses clinic.
      RESULTS: 301 patients were identified: 260 had isolated MGLSc and 41 both MGLSc
      and PeIN. Referrals were made from the local Urology and Andrology departments
      (128), primary care (89), GUM (54), other dermatology departments (28) and other
      specialties (2). In isolated MGLSc, 94.6% were diagnosed clinically with 93.5%
      accuracy (based on data from subsequent circumcisions). In combined MGLSc/PeIN,
      85.4% were diagnosed following diagnostic biopsy and 14.6% retrospectively after
      circumcision. In isolated MGLSc, 50% were treated topically, and 50% required
      surgery. In MGLSc/PeIN, 78% required surgical interventions. In isolated MGLSc,
      92.2% achieved resolution of symptoms, 3.5% were awaiting procedures, and 4.8%
      were receiving ongoing topical therapy. In MGLSc/PeIN, 90.2% achieved clearance,
      2.4% were waiting surgery, and 7.3% were treated topically. Only 2.7% reported
      ongoing symptoms, all in patients treated surgically. None progressed to PSCC.
      DISCUSSION: MGLSc is generally a disease of the uncircumcised; the majority of
      cases of MGLSc are accurately diagnosed clinically; suspected PeIN or PSCC
      requires histological confirmation; circumcision histology can be non-specific;
      most men are either cured by topical treatment with ultrapotent corticosteroid
      (53.1%) or by circumcision (46.9%); surgical intervention is required in most
      cases of concomitant MGLSc and PeIN; the majority of patients with MGLSc alone or
      with MGLSc and PeIN remit with this approach; effective management appears to
      negate the risk of malignant transformation to PSCC.

PMID- 28750141
TI  - Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in
      Denmark: A nationwide cohort study.
AB  - Cirrhosis in patients with chronic hepatitis C increases the risk of
      hepatocellular carcinoma (HCC), and surveillance with ultrasound (US) and alpha
      fetoprotein (AFP) is recommended. This study aimed to estimate changes in the HCC
      incidence rate (IR) over time, HCC stage and prognosis, and AFP and US performed
      in patients with hepatitis C and cirrhosis. Eligible patients were identified in
      the Danish Database for Hepatitis B and C, and data from national health
      registries and patient charts were obtained. Tumour stage was based on Barcelona
      Clinic Liver Cancer stage, TNM classification and size and number of lesions
      combined into stages 0-3. We included 1075 patients with hepatitis C and
      cirrhosis, free of HCC and liver transplant at baseline. During 4988 person years
      (PY), 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100
      PY [CI95% 0.4-1.5] in 2002-2003 to 2.9/100 PY [2.4-3.4] in 2012-2013. One-year
      cumulative incidence of at least one AFP or US was 53% among all patients. The
      positive predictive value of an AFP >= 20 ng mL-1 was 17%. Twenty-three (21%)
      patients were diagnosed with early-stage HCC (stage 0/1) and 84 (79%) with late
      stage. Median survival after HCC for early-stage HCC disease was 30.1 months and
      7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over
      time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP
      and US was suboptimal, and most patients were diagnosed with advanced HCC with a
      poor prognosis.

PMID- 28750142
TI  - Feline leukocyte adhesion (CD18) deficiency caused by a deletion in the integrin
      beta2 (ITGB2) gene.
AB  - BACKGROUND: Leukocyte adhesion deficiency (LAD) or CD18 deficiency is an
      autosomal recessive immunodeficiency which has been described in people, cattle,
      dogs, and knockout mice. OBJECTIVES: The study goals were to characterize the
      clinicopathologic, immunologic, and molecular genetic features of feline LAD
      (FLAD) in a neutered male adult Domestic Longhair cat with severe leukocytosis
      and recurrent infections. METHODS: Flow cytometry evaluated surface expression of
      CD18 on neutrophils. In vitro functional assays assessed CD18-dependent
      neutrophil adhesion and T-cell proliferation. Genomic DNA and cDNA were used to
      identify a causative mutation in the coding sequence of the integrin beta2
      subunit (ITGB2) gene. RESULTS: The affected cat developed periodontitis during
      the first months of life followed by recurrent infections poorly responsive to
      antibiotic therapy, accompanied by extreme neutrophilia. Neutrophils from the
      proband, compared to feline controls, did not express any CD18 on the cell
      surface. Adhesion of affected neutrophils was severely impaired with and without
      phorbol-myristate-acetate activation. The proband's T-cells proliferated weakly
      to 1 pg but normally to 100 pg staphylococcal enterotoxin A, suggesting a CD18
      independent T-cell response at higher doses. Molecular genetic analysis of the
      ITGB2 gene revealed a 24 bp deletion at the exon 2 to intron 2 boundary (c.46_58
      + 11del), predicting premature translational termination due to abnormal splicing
      of exon 1 to exon 3 or 4. CONCLUSIONS: Feline LAD exhibits features similar to
      LAD in other species. However, clinical episodes in FLAD appeared milder allowing
      for an extended life expectancy under long-term antimicrobial therapy, possibly
      due to an alternative, CD18-independent T-cell proliferation pathway.

PMID- 28750143
TI  - Characterization of Small-Molecule Scaffolds That Bind to the Shigella Type III
      Secretion System Protein IpaD.
AB  - Many pathogens such as Shigella and other bacteria assemble the type III
      secretion system (T3SS) nanoinjector to inject virulence proteins into their
      target cells to cause infectious diseases in humans. The rise of drug resistance
      among pathogens that rely on the T3SS for infectivity, plus the dearth of new
      antibiotics require alternative strategies in developing new antibiotics. The
      Shigella T3SS tip protein IpaD is an attractive target for developing anti
      infectives because of its essential role in virulence and its exposure on the
      bacterial surface. Currently, the only known small molecules that bind to IpaD
      are bile salt sterols. In this study we identified four new small-molecule
      scaffolds that bind to IpaD, based on the methylquinoline, pyrrolidine-aniline,
      hydroxyindole, and morpholinoaniline scaffolds. NMR mapping revealed potential
      hotspots in IpaD for binding small molecules. These scaffolds can be used as
      building blocks in developing small-molecule inhibitors of IpaD that could lead
      to new anti-infectives.

PMID- 28750144
TI  - Therapy of ulcus cruris of venous and mixed venous arterial origin with
      autologous, adult, native progenitor cells from subcutaneous adipose tissue: a
      prospective clinical pilot study.
AB  - BACKGROUND: The stromal vascular fraction (SVF) of adipose tissue consists of
      cellular subpopulations with distinct regenerative potential. OBJECTIVE: To
      investigate the regenerative capacities of autologous SVF cells in the treatment
      of chronic leg ulcers of venous (VLU) and arterial-venous (AVLU) origin. METHODS:
      Multimorbid ulcer patients received a singular topical treatment with 9-15 * 106
      SVF cells, separated from abdominal lipoaspirates by digestion with collagenase
      and neutral protease and applied immediately after isolation. The primary
      endpoints were the change in wound size 12 weeks after treatment and evaluation
      of adverse events. Secondary endpoints included the time to complete wound
      epithelialization and change in pain levels. Postoperative wound treatment
      modalities and treatment of comorbidities were not intensified compared with pre
      operative management. Follow-up period was at least 6 months. RESULTS: Sixteen
      elderly ulcer patients (seven with VLU, nine with AVLU) were treated as
      described. All VLU patients (median ulcer size: 48.25 cm2 ) and four of nine AVLU
      patients showed complete epithelialization of the ulcers within 71-174 days. In
      three patients with large ulcerations on both legs, ulcerations on the non
      treated, contralateral leg also epithelialized. Patients reported a considerable
      rapid decrease in pain intensity by 2.5 points on average on a visual scale from
      1 to 5 within the first 2 weeks after treatment. The patients were followed up
      for 9-44 months (median: 30 months). No severe side-effects were observed.
      CONCLUSIONS: The use of SVF cells presents an effective, minimally invasive
      option for the treatment of VLU and AVLU even in multimorbid patients. In
      patients with larger predominantly ischaemic AVLU and comorbidities, one-time
      application of the used amounts of SVF cells was not sufficient in the majority
      of cases.

PMID- 28750145
TI  - Severity assessments used for inclusion criteria and baseline severity evaluation
      in atopic dermatitis clinical trials: a systematic review.
AB  - BACKGROUND: Numerous inclusion criteria and baseline severity assessments are
      used in clinical trials of atopic dermatitis (AD), which may limit comparison of
      results. OBJECTIVE: We sought to characterize the inclusion criteria and baseline
      severity assessments used in randomized controlled trials (RCT) of AD
      internationally. METHODS: We performed a systematic review of RCT with a
      pharmacological intervention from 2007 to 2016. Cochrane Library, EMBASE, GREAT,
      LILACS, MEDLINE and Scopus were searched. Two authors independently performed
      study selection and data extraction. RESULTS: Overall, 212 RCT met
      inclusion/exclusion criteria. Target population and inclusion criteria based on
      AD severity were not documented in 78 (36.8%) and 25 (18.7%) studies,
      respectively. Thirty and 58 severity assessments were used for inclusion criteria
      and baseline severity, respectively, with only 60.3% concordance between their
      uses. Global assessments were most frequently used for both inclusion criteria
      and baseline severity assessment in North America (39.5% and 32.1%), while
      SCORing AD (SCORAD) or objective-SCORAD index was most frequently used in Europe
      (23.5% and 23.0%) and Asia (34.2% and 43.5%). Minimum and maximum thresholds of
      severity assessments were inconsistently used between studies for inclusion
      criteria, even within similar target populations. SCORAD, global assessments and
      body surface area were most frequently used for both inclusion criteria and
      baseline severity assessment. IGA was particularly used in trials of topical
      agents. CONCLUSIONS: There were considerable variability and poor documentation
      of inclusion criteria and baseline severity assessments in RCT for AD. These
      differences may limit interpretation of a study and comparison of results between
      studies.

PMID- 28750146
TI  - Prevalence and initial prescription of psychotropics in patients with common
      cancers in Japan, based on a nationwide health insurance claims database.
AB  - OBJECTIVE: To investigate the prevalence of psychotropic medication use and
      identify factors affecting the prescription of psychotropics among patients newly
      diagnosed with any of 8 common types of cancer. METHODS: This retrospective
      descriptive study examined data for patients newly diagnosed with breast,
      colorectal, liver, lung, ovarian, pancreatic, prostate, or stomach cancer between
      July 2009 and May 2014. The data were derived from a nationwide health claims
      database. The proportion of initial prescriptions for all oral psychotropics
      within 13 months of cancer diagnosis was analyzed by cancer type; the odds ratio
      (OR) for prescribing psychotropics was calculated using multivariable logistic
      regression models. RESULTS: A total of 14 661 patients were newly diagnosed with
      cancer. Psychotropics were prescribed for 6593 (45%) patients. The highest and
      lowest proportions of psychotropic prescriptions were recorded for patients with
      lung cancer (62.6%) and prostate cancer (35.1%), respectively. The strongest
      predictors for psychotropic prescriptions were chemotherapy (OR, 2.59; 95%
      confidence interval [CI], 2.31-2.91; P < .001), lung cancer (OR, 2.47; 95% CI,
      2.16-2.83; P < .001), and surgery (OR, 2.12; 95% CI, 1.97-2.28; P < .001).
      CONCLUSIONS: The prevalence of and predictors for an initial prescription of
      psychotropics identified a potential target population of cancer patients
      requiring psychiatric treatment, particularly soon after a diagnosis of cancer.

PMID- 28750147
TI  - Microcatheter balloon pinning technique to facilitate wiring of a left circumflex
      chronic total occlusion.
AB  - INTRODUCTION: Coronary chronic total occlusions (CTOs) are commonly encountered
      during diagnostic angiograms. With recent advances, especially in experienced
      centers, success rates with CTO percutaneous coronary intervention (PCI) have
      approached 80% or higher. It is important to note that despite these advancements
      in techniques, CTOs remain difficult to treat. We present a case of a left
      circumflex artery (LCX) CTO that was successfully revascularized using a
      microcatheter balloon pinning technique that allowed additional wire support.
      CASE REPORT: A 77-year-old woman status post-two-vessel coronary artery bypass
      graft surgery presented with new onset angina at rest and was found to have a
      patent graft to the left anterior descending artery, and an unrevascularized
      proximal LCX CTO. PCI was attempted with a microcatheter using an antegrade
      approach. This approach was unsuccessful due to the lack of support and the left
      circumflex angle. As a result, we used a balloon to pin the microcatheter to the
      wall of the left main to allow for successful wiring of the LCX. A stent was
      successfully deployed in the LCX, and the patient was discharged from the
      hospital 2 days later. At follow-up, the patient was asymptomatic and returned to
      her usual activity. DISCUSSION: After conducting a thorough literature search, it
      appears that this is the first case that a microcatheter has been pinned with a
      balloon. We believe that in LCX CTOs that require support, the microcatheter
      pinning technique can provide adequate support in wiring CTO's. LCX CTOs can be
      very difficult to treat, we present a case of a LCX CTO that required the use of
      the microcatheter balloon pinning technique to allow additional wire support for
      successful wiring and ultimately treatment.

PMID- 28750148
TI  - Analytic variability in the enumeration of neutrophil subpopulations in canine
      blood.
AB  - BACKGROUND: Conventional differential leukocyte counts do not enumerate
      hyposegmented neutrophils (Hypo-PMN), ie, immature neutrophils that already lost
      the band morphology but are not yet completely segmented. They may be early
      indicators of acute inflammation. OBJECTIVES: The purpose of the study was to
      evaluate the analytic variability of counts of segmented neutrophils (Seg-PMN),
      band neutrophils (Band), hyposegmented neutrophils (Hypo-PMN), non-Bands (Hypo
      PMN + Seg-PMN), and Young-PMN (Bands + Hypo-PMN) assess if Hypo- or Young-PMN
      identify inflammation better than Bands. METHODS: Neutrophil subpopulations were
      counted by 2 observers on 2 sets of 100 cells in 267 blood smears from dogs with
      changes potentially consistent with inflammation to calculate the intra- and
      inter-observer variability. RESULTS: Median intra-observer CVs were < 5.0% for
      Seg-PMN and non-Bands, and 20.0% and 28.0% for Hypo-PMN and Young-PMN for
      observer 1 and 2, respectively; median inter-observer CVs for Seg-PMN, non-Bands,
      Hypo-PMN, and Young-PMN were 4.6%, 5.0%, 60.0%, and 47.1%, respectively. Median
      CV of Band counts in blood smears with bands was 141%. CONCLUSIONS: The analytic
      variability of Hypo- and Young-PMN is lower than that of Bands. This
      retrospective study did not allow us to investigate the diagnostic potential or
      the clinical relevance of these cells. However, the low inter- and intra-observer
      variabilities with these cell populations suggest that the count of Hypo- or
      Young-PMN may better identify acute inflammation than the count of Bands.

PMID- 28750149
TI  - Single-Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II
      Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment.
AB  - Azilsartan medoxomil (AZL-M) is a potent angiotensin II receptor blocker that
      decreases blood pressure in a dose-dependent manner. It is a prodrug that is not
      detected in blood after its oral administration because of its rapid hydrolysis
      to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the
      major metabolite, M-II, and minor metabolites. The objective of this study was to
      determine the effect of mild to moderate hepatic impairment on the
      pharmacokinetics of AZL and its major metabolite. This was a single-center, open
      label, phase 1 parallel-group study that examined the single-dose (day 1) and
      multiple-dose (days 4-8) - 40 mg - pharmacokinetics of AZL and M-II in 16
      subjects with mild and moderate hepatic impairment by Child-Pugh classification
      (n = 8 per group) and subjects (n = 16) matched based on age, sex, race, weight,
      and smoking status. Mild or moderate hepatic impairment did not cause clinically
      meaningful increases in exposure to AZL and M-II. Mild or moderate hepatic
      impairment had no clinically meaningful effect on the plasma protein binding of
      AZL and M-II. Single and multiple doses of AZL-M 40 mg were well tolerated in all
      subject groups. Based on the pharmacokinetic and tolerability findings, no dose
      adjustment of AZL-M is required for subjects with mild and moderate hepatic
      impairment.

PMID- 28750150
TI  - Are checkpoint inhibitors a valuable option for metastatic or unresectable vulvar
      and vaginal melanomas?

PMID- 28750151
TI  - Pharmacokinetics and Safety of Brexpiprazole Following Multiple-Dose
      Administration to Japanese Patients With Schizophrenia.
AB  - Brexpiprazole is currently approved in the United States for the treatment of
      schizophrenia and as adjunctive treatment of major depressive disorder. In
      Canada, it is approved for the treatment of schizophrenia. This study evaluated
      the pharmacokinetics (PK) and safety of brexpiprazole in Japanese patients with
      schizophrenia. This phase 1 study comprised a 14-day multiple-dose administration
      of brexpiprazole 1, 4, and 6 mg/day (n = 7, 8, and 6, respectively). Plasma
      concentrations and PK parameters and the influence of CYP2D6 polymorphisms
      (intermediate metabolizers [IMs] and extensive metabolizers [EMs]) on PK were
      evaluated. Adverse events (AEs) were recorded. The Cmax and AUC24h of
      brexpiprazole and its metabolite, DM-3411, showed dose-proportionality. The Cmax
      and AUC24h of brexpiprazole showed accumulation of about 2.5- to 5.5-fold on day
      14, compared with those on day 1. The median tmax and the mean elimination half
      life of brexpiprazole were 4-5 and 52-92 hours, respectively, across all doses on
      day 14. The C24h of brexpiprazole reached steady state after day 10 in all dose
      groups. The dose-normalized Cmax and AUC24h of brexpiprazole on day 14 were
      higher in IM patients than in EM patients. AEs were generally mild to moderate,
      with transient serum prolactin increase being the most common event. No
      clinically significant changes were observed for other clinical laboratory
      values. Brexpiprazole was safe and well tolerated in the studied Japanese
      patients with schizophrenia.

PMID- 28750152
TI  - Left atrial appendage occlusion for stroke prevention in patients with atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is a commonly sustained atrial arrhythmia with
      associated morbidity and mortality. AF is associated with increased risk of
      thromboembolism and stroke, requiring use of anticoagulation. Anticoagulation
      decreases the risk of stroke but is associated with a higher risk of bleeding,
      necessitating discontinuation in some patients. The left atrial appendage is the
      likely source of thrombus in the majority of patients with AF. This has led to
      the development of left atrial appendage occlusion as a means to reduce stroke
      risk in patients who have a contraindication to long-term anticoagulation.
      Multiple implantable devices have surfaced in the last few years, with some
      promising prospects. The main purpose of this review is to highlight the
      indications and use of these devices for left atrial appendage occlusion.

PMID- 28750153
TI  - Safety and efficacy of dual-wavelength laser (1064 + 595 nm) for treatment of non
      treated port-wine stains.
AB  - BACKGROUND: Patients with port-wine stain (PWS) suffer physically and
      psychologically because of the high incidence (0.3%-0.5%) of the disease. Pulsed
      dye laser (PDL) at 595 nm is the gold standard of the treatment for PWS.
      Nevertheless, clinicians intend to determine whether the dual-wavelength laser
      (DWL; 595-nm PDL + 1064-nm Nd:YAG) is an adequate choice in the treatment of non
      treated PWS. This study is the first prospective within-patient controlled
      research seeking to investigate the safety and efficacy of DWL for the treatment
      of non-treated PWS. METHODS: A total of 61 patients with non-treated flat facial
      PWS, who were treated using the Cynergy laser system in our clinic, were included
      in this study. Each PWS lesion was divided into two adjacent test treatment sites
      of similar size and colour. The two sites were randomly assigned to PDL or DWL
      treatment in a blinded manner of participants. In each case, two sets of
      treatment parameters were used: (i) 595-nm PDL and (ii) 595-nm PDL + 1064-nm
      Nd:YAG. Both had a 10 mm spot size, an epidermal cooling system and 1-s
      interpulse interval between two pulses. Clinical efficacy and safety outcomes
      were evaluated by visual assessment 2 months after treatment. RESULTS: Comparison
      by visual evaluation suggests that the responses of non-treated PWS to treatment
      by PDL and DWL were not significantly different. Moreover, three patients
      developed scarring after DWL treatment. CONCLUSION: Compared with PDL, DWL
      exhibits a higher risk of potential scarring and has no advantage in efficacy of
      treating non-treated PWS.

PMID- 28750154
TI  - Skin hydration, microrelief and greasiness of normal skin in Antarctica.
AB  - BACKGROUND: The skin is the primary defence of the human body against external
      factors from physical, chemical, mechanical and biologic origin. Climatic factors
      together with low temperature and sun radiation affect the skin. The effect of
      climatic conditions in Antarctica on healthy skin has not been previously
      addressed. OBJECTIVES: The aim of this study was to evaluate the changes in the
      skin hydration, greasiness and microrelief due to the extreme climatic
      environmental factors during the stay of the members of the Bulgarian Antarctic
      expedition. MATERIAL AND METHODS: Fifty-nine Caucasian healthy subjects, 42 men
      and 17 women with mean age 50.9 years (27-68), were enrolled. The study was
      performed in five consecutive years from 2011 to 2016 at the Bulgarian Antarctic
      base camp at Livingston Island. The study protocol consisted of two parts: study
      A: duration of 15 days with measurement of skin physiology parameters on a daily
      basis, and study B: five measurements at baseline and at days 14, 30, 45 and 50
      upon arrival in Antarctica. We measured three biophysical parameters related to
      skin physiology at cheek skin by an impedance measuring device. RESULTS: No
      statistically significant difference between parameters at the different
      measurement points. There is a variation in skin hydration reaching its lower
      point at day 11 and then returning to values similar to baseline. Initially, an
      increase in skin greasiness was witnessed with a sharp depression at day 11 and
      final values at day 15 resembling the ones at baseline. An increase, although not
      statistically significant, in skin roughness was observed in the first 15 days of
      the study. Study B showed no statistically significant variances between values
      of the three parameters. CONCLUSION: Our studies show the pioneer results of the
      effect of Antarctic climate on human skin physiology.

PMID- 28750155
TI  - A comparison using Faraday cups with 1013 Omega amplifiers and a secondary
      electron multiplier to measure Os isotopes by negative thermal ionization mass
      spectrometry.
AB  - RATIONALE: According to the Johnson-Nyquist noise equation, the value of electron
      noise is proportional to the square root of the resistor value. This relationship
      gives a theoretical improvement of 100 in the signal/noise ratio by going from
      1011 Omega to 1013 Omega amplifiers for Faraday detection in thermal ionization
      mass spectrometry (TIMS). METHODS: We measured Os isotopes using static Faraday
      cups with 1013 Omega amplifiers in negative thermal ionization mass spectrometry
      (NTIMS) and compared the results with those obtained with 1011 Omega amplifiers
      and by peak-hopping on a single secondary electron multiplier (SEM). We analysed
      large loads of Os (1 MUg) at a range of intensities of 187 OsO3 (0.02-10 mV) in
      addition to small loads of Os (5-500 pg) to compare the results of the three
      methods. RESULTS: Using 1013 Omega amplifiers, the long-term reproducibility
      determined from Merck Os was 187 Os/188 Os = 0.1211 +/- 0.0086 and 0.120229 +/-
      0.000034 at 0.02 mV and 10 mV of 187 OsO3 intensities. Meanwhile, the analysed
      JMC Os loadings of 5 and 500 pg showed 187 Os/188 Os = 0.10669 +/- 0.00036 and
      0.106807 +/- 0.000023. In comparison, the values measured by the SEM were 187
      Os/188 Os = 0.10704 +/- 0.00056 and 0.10690 +/- 0.00013. All errors are in 2
      standard deviation (SD). CONCLUSIONS: Both the accuracy and the precision
      determined using the 1013 Omega amplifiers and the SEM are identical when the Os
      amounts are within 10-50 pg. However, the former analysis time can be shortened
      by approximately two-thirds. The SEM measurement is still the most precise method
      for Os amounts <10 pg, but the analyses using 1013 Omega amplifiers suggest they
      are significantly better than the SEM for Os amounts >50 pg.

PMID- 28750156
TI  - Psychiatric conditions as predictors of rehospitalization among African American
      patients hospitalized with heart failure.
AB  - INTRODUCTION: African Americans (AAs) have the highest risk of developing heart
      failure (HF) among all ethnicities in the United States and are associated with
      higher rates of readmissions and mortality. This study aims to determine the
      prevalence and relationship of common psychiatric conditions to outcomes of
      patients hospitalized with HF. HYPOTHESIS: Psychiatric conditions lead to worse
      outcomes in HF patients. METHODS: This single-center retrospective study enrolled
      611 AA patients admitted to an urban teaching community hospital for HF from 2010
      to 2013. Patient demographics, clinical variables, and history of psychiatric
      disorders were obtained. Cox proportional hazards regression was used to assess
      impact of psychiatric disorders on readmission rates and mortality. RESULTS: The
      mean age was 66 +/- 15 years; 53% were men. Median follow-up time from index
      admission for HF was 3.2 years. Ninety-seven patients had a psychiatric
      condition: 46 had depression, 11 had bipolar mood disorder (BMD), and 40 had
      schizophrenia. After adjustment of known risk factors and clinical metrics, our
      study showed that AA HF patients with a psychiatric illness were 3.84* more
      likely to be admitted within 30 days for HF, compared with those without (P <
      0.001). Individually, adjusted Cox multivariable logistic regression analysis
      also showed that, for 30-day readmission, schizophrenia had a hazard ratio (HR)
      of 4.92 (P < 0.001); BMD, an HR of 3.44 (P = 0.02); and depression, an HR 3.15 (P
      = 0.001). No associations were found with mortality. CONCLUSIONS: Psychiatric
      conditions of schizophrenia, BMD, and depression were significantly associated
      with a higher 30-day and overall readmission rate for HF among AA patients.

PMID- 28750157
TI  - From the Editors.

PMID- 28750158
TI  - Scenario Building and Sensitivity Analyses for Decision Support: A Response to D.
      Warner North.

PMID- 28750159
TI  - Commentary on Cost-Benefit Analysis Article for Nuclear Waste Management.

PMID- 28750160
TI  - Two Phase 1, Open-Label, Mass Balance Studies to Determine the Pharmacokinetics
      of 14 C-Labeled Isavuconazonium Sulfate in Healthy Male Volunteers.
AB  - Isavuconazonium sulfate is the water-soluble prodrug of the active triazole
      isavuconazole. Two phase 1 studies were conducted to identify the metabolic
      profile and mass balance of isavuconazole and BAL8728 (inactive cleavage
      product). Seven subjects in study 1 (isavuconazole mass balance) received a
      single oral dose of [cyano-14 C]isavuconazonium sulfate corresponding to 200 mg
      isavuconazole. Six subjects in study 2 (BAL8728 mass balance) received a single
      intravenous dose of [pyridinylmethyl-14 C]isavuconazonium sulfate corresponding
      to 75 mg BAL8728. Pharmacokinetic parameters of radioactivity in whole blood and
      plasma and of isavuconazole and BAL8728 in plasma were assessed. Radioactivity
      ratio of blood/plasma, percentage of dose, and cumulative percentage of
      radioactive dose recovered in urine and feces for isavuconazole and BAL8728 were
      assessed. Metabolic profiling was carried out by high-performance liquid
      chromatography and mass spectrometry. Mean plasma isavuconazole pharmacokinetic
      parameters included apparent clearance (2.3 +/- 0.7 L/h), apparent volume of
      distribution (301.8 +/- 105.7 L), and terminal elimination half-life (99.9 +/-
      44.6 hours). In study 1, isavuconazole-derived radioactivity was recovered
      approximately equally in urine and feces (46.1% and 45.5%, respectively). In
      study 2, BAL8728-derived radioactivity was predominantly recovered in urine
      (96.0%). Isavuconazole (study 1) and M4 (cleavage metabolite of BAL8728; study 2)
      were the predominant circulating components of radioactivity in plasma.

PMID- 28750161
TI  - Facile and Scalable Synthesis of Zn3V2O7(OH)2.2H2O Microflowers as a High
      Performance Anode for Lithium-Ion Batteries.
AB  - The employment of nanomaterials and nanotechnologies has been widely acknowledged
      as an effective strategy to enhance the electrochemical performance of lithium
      ion batteries (LIBs). However, how to produce nanomaterials effectively on a
      large scale remains a challenge. Here, the highly crystallized Zn3V2O7(OH)2.2H2O
      is synthesized through a simple liquid phase method at room temperature in a
      large scale, which is easily realized in industry. Through suppressing the
      reaction dynamics with ethylene glycol, a uniform morphology of microflowers is
      obtained. Owing to the multiple reaction mechanisms (insertion, conversion, and
      alloying) during Li insertion/extraction, the prepared electrode delivers a
      remarkable specific capacity of 1287 mA h g-1 at 0.2 A g-1 after 120 cycles. In
      addition, a high capacity of 298 mA h g-1 can be obtained at 5 A g-1 after 1400
      cycles. The excellent electrochemical performance can be attributed to the high
      crystallinity and large specific surface area of active materials. The smaller
      particles after cycling could facilitate the lithium-ion transport and provide
      more reaction sites. The facile and scalable synthesis process and excellent
      electrochemical performance make this material a highly promising anode for the
      commercial LIBs.

PMID- 28750162
TI  - Drug Specificity, Synergy and Antagonism in Ultrahigh Capacity Poly(2
      oxazoline)/Poly(2-oxazine) based Formulations.
AB  - Polymer micelles offer the possibility to create a nanoscopic environment that is
      distinct from the bulk phase. They find applications in catalysis, drug delivery,
      cleaning, etc. Often, one simply distinguishes between hydrophilic and
      hydrophobic, but fine-tuning of the microenvironment is possible by adjusting the
      structure of the polymer amphiphile. Here, we investigated a small library of
      structurally similar amphiphiles based on poly(2-oxazoline)s and poly(2-oxazine)s
      with respect to their solubilization capacity for two extremely water insoluble
      drugs, curcumin and paclitaxel. We found very significant and orthogonal
      specificities even if only one methylene group is exchanged between the polymer
      backbone and side chain. More strikingly, we observed profound synergistic and
      antagonistic solubilization patterns for the coformulation of the two drugs. Our
      findings shed new light on host-guest interaction in polymer micelles and such
      pronounced host-guest specificities in polymer micelles may not only be
      interesting in drug delivery but also for applications such as micellar
      catalysis.

PMID- 28750163
TI  - Salt Gradient Modulation of MicroRNA Translocation through a Biological Nanopore.
AB  - In resistive pulse sensing of microRNA biomarkers, selectivity is achieved with
      polynucleotide-extended DNA probes, with the unzipping of a miRNA-DNA duplex in
      the nanopore recorded as a resistive current pulse. As the assay sensitivity is
      determined by the pulse frequency, we investigated the effect of cis/trans
      electrolyte concentration gradients applied over alpha-hemolysin nanopores. KCl
      gradients were found to exponentially increase the pulse frequency, while
      reducing the preference for 3'-first pore entry of the duplex and accelerating
      duplex unzipping, all manifestations of an enhanced electrophoretic force. Unlike
      silicon nitride pores, a counteracting contribution from electro-osmotic flow
      along the pore wall was not apparent. Significantly, a gradient of 0.5/4 M KCl
      increased the pulse frequency ~60-fold with respect to symmetrical 1 M KCl, while
      the duplex dwell time in the nanopore remained acceptable for pulse detection and
      could be extended by LiCl addition. Steeper gradients caused lipid bilayer
      destabilization and pore instability, limiting the total number of recorded
      pulses. The 8-fold KCl gradient enabled a linear relationship between pulse
      frequency and miRNA concentration for the range of 0.1-100 nM. This work
      highlights differences between biological and solid-state nanopore sensing and
      provides strategies for subnanomolar miRNA quantification with bilayer-embedded
      porins.

PMID- 28750164
TI  - Fast Transport of Water Droplets over a Thermo-Switchable Surface Using
      Rewritable Wettability Gradient.
AB  - In spite of the reported temperature dependent tunability in wettability of
      poly(N-isopropylacrylamide) (PNIPAAm) surfaces for below and above lower critical
      solution temperature (32  degrees C), the transport of water droplets is
      inhibited by the large contact angle hysteresis. Herein, for the first time, we
      report on-demand, fast, and reconfigurable droplet manipulation over a PNIPAAm
      grafted structured polymer surface using temperature-induced wettability
      gradient. Our study reveals that the PNIPAAm grafted on intrinsically
      superhydrophobic surfaces exhibit hydrophilic nature with high contact angle
      hysteresis below 30  degrees C and superhydrophobic nature with ultralow contact
      angle hysteresis above 36  degrees C. The transition region between 30 and 36 
      degrees C is characterized by a large change in water contact angle (~100 degrees
      ) with a concomitant change in contact angle hysteresis. By utilizing this
      "transport zone" wherein driving forces overcome the frictional forces, we
      demonstrate macroscopic transport of water drops with a maximum transport
      velocity of approximately 40 cm/s. The theoretical calculations on the force
      measurements concur with dominating behavior of driving forces across the
      transport zone. The tunability in transport velocity by varying the temperature
      gradient along the surface or the inclination angle of the surface (maximum angle
      of 15 degrees  with a reduced velocity 0.4 mm/s) is also elucidated. In addition,
      as a practical application, coalescence of water droplets is demonstrated by
      using the temperature controlled wettability gradient. The presented results are
      expected to provide new insights on the design and fabrication of smart
      multifunctional surfaces for applications such as biochemical analysis, self
      cleaning, and microfluidics.

PMID- 28750165
TI  - Synthesis and Electrophoretic Concentration of Cadmium Sulfide Nanoparticles in
      Reverse Microemulsions of Tergitol NP-4 in n-Decane.
AB  - The kinetics of thiourea synthesis of CdS nanoparticles (NPs) in reverse
      microemulsions of Tergitol Np-4/n-decane was studied in the temperature range of
      313-333 K by spectrophotometry, photon-correlation spectroscopy, and transmission
      electron microscopy. The formation of NPs is described by the kinetic model,
      including two consecutive steps: homogeneous nucleation in a solution as the
      first step and the autocatalytic growth of NPs due to heterogeneous reaction on a
      continuously increasing surface as the second step. Effective rate constants of
      the steps (k1 = 1.52 * 10-2-1.75 * 10-3 s-1 and k2 = 4.9 * 10-1-5.1 * 10-2 M-1 s
      1) and effective activation energies (Ea1 = 156 and Ea2 = 149 kJ/mol) were
      estimated in the pseudo-first-order reaction with respect to cadmium (cCd = 0.9
      mM, cThio = 9 mM). The obtained constants were used to calculate the dependence
      of nanoparticle diameter on the synthesis time (d3 ~ t). The calculated values
      correlate well with experimental data of photon-correlation spectroscopy and
      transmission electron microscopy.

PMID- 28750167
TI  - Comparison of Antioxidant Evaluation Assays for Investigating Antioxidative
      Activity of Gallic Acid and Its Alkyl Esters in Different Food Matrices.
AB  - The addition of antioxidants is one of the strategies to inhibit lipid oxidation,
      a major cause of lipid deterioration in foods leading to rancidity development
      and nutritional losses. However, several studies have been reported that
      conventional antioxidant assays, e.g., TPC, ABTS, FRAP, and ORAC could not
      predict antioxidant performance in several foods. This study aimed to investigate
      the performance of two recently developed assays, e.g., the conjugated
      autoxidizable triene (CAT) and the apolar radical-initiated conjugated
      autoxidizable triene (ApoCAT) assays to predict the antioxidant effectiveness of
      gallic acid and its esters in selected food models in comparison with the
      conventional antioxidant assays. The results indicated that the polarities of the
      antioxidants have a strong impact on antioxidant activities. In addition,
      different oxidant locations demonstrated by the CAT and ApoCAT assays influenced
      the overall antioxidant performances of the antioxidants with different
      polarities. To validate the predictability of the assays, the antioxidative
      performance of gallic acid and its alkyl esters was investigated in oil-in-water
      (O/W) emulsions, bulk soybean oils, and roasted peanuts as the lipid food models.
      The results showed that only the ApoCAT assay could be able to predict the
      antioxidative performances in O/W emulsions regardless of the antioxidant
      polarities. This study demonstrated that the relevance of antioxidant assays to
      food models was strongly dependent on physical similarities between the tested
      assays and the food structure matrices.

PMID- 28750168
TI  - Molecular Dynamics of Cyclodextrins in Water Solutions from NMR Deuterium
      Relaxation: Implications for Cyclodextrin Aggregation.
AB  - The aggregation of the most common natural cyclodextrins (alpha-, beta-, and
      gamma-) in aqueous solutions is addressed by studying the CD-CD interactions
      using deuterium relaxation rates for deuterium labeled CDs. Relaxation times (T1)
      and their corresponding relaxation rates (R1 = 1/T1) provide information about
      the rotational correlation times of CDs and serve as a proxy for solute-solute
      interactions. Measured T1's for alpha-, beta-, and gamma-CD at the lowest CD
      concentrations were in agreement with predictions of a hydrodynamic model for
      toroids, in particular with regard to the dependence of T1 on CD size. On the
      other hand, the dependence of T1's with respect to the increase in CD
      concentration could not be explained by hydrodynamic or direct interaction
      between CD molecules, and it is suggested that there is an equilibrium between
      monomeric and dimeric CD to account for the observed concentration dependence. No
      evidence in favor of large aggregates of CDs involving a non-negligible fraction
      was found for the investigated CDs.

PMID- 28750166
TI  - Repair-Resistant DNA Lesions.
AB  - The eukaryotic global genomic nucleotide excision repair (GG-NER) pathway is the
      major mechanism that removes most bulky and some nonbulky lesions from cellular
      DNA. There is growing evidence that certain DNA lesions are repaired slowly or
      are entirely resistant to repair in cells, tissues, and in cell extract model
      assay systems. It is well established that the eukaryotic DNA lesion-sensing
      proteins do not detect the damaged nucleotide, but recognize the
      distortions/destabilizations in the native DNA structure caused by the damaged
      nucleotides. In this article, the nature of the structural features of certain
      bulky DNA lesions that render them resistant to NER, or cause them to be repaired
      slowly, is compared to that of those that are good-to-excellent NER substrates.
      Understanding the structural features that distinguish NER-resistant DNA lesions
      from good NER substrates may be useful for interpreting the biological
      significance of biomarkers of exposure of human populations to genotoxic
      environmental chemicals. NER-resistant lesions can survive to replication and
      cause mutations that can initiate cancer and other diseases. Furthermore, NER
      diminishes the efficacy of certain chemotherapeutic drugs, and the design of more
      potent pharmaceuticals that resist repair can be advanced through a better
      understanding of the structural properties of DNA lesions that engender repair
      resistance.

PMID- 28750169
TI  - Ticketing aggressive cars and trucks (TACT): How does it work on city streets?
AB  - OBJECTIVE: The purpose of this study was to determine the feasibility of
      modifying the Ticking Aggressive Cars and Trucks (TACT) program, originally
      designed to work on state highways, within a metropolitan area to reduce unsafe
      interactions and their related crashes between drivers of large trucks and
      passenger vehicles. METHODS: Using crash data, the driving behaviors most
      commonly associated with large truck and passenger vehicle crashes were
      identified. A public awareness campaign using media messaging and increased law
      enforcement was created targeting these associated behaviors. The frequency of
      these behaviors both before and after the public awareness campaign was
      determined through observation of traffic at 3 specific locations within the
      city. Each location had a sufficient volume of large truck and passenger traffic
      to observe frequent interactions. Pre- and postintervention data were compared
      using negative binomial regression with generalized estimating equations to
      evaluate whether the campaign was associated with a reduction in the identified
      driving behaviors. RESULTS: A comparison between crash data from before, during,
      and after the campaign and crashes during the same time periods in previous years
      did not show a significant difference (P =.081). The number of large trucks
      observed in traffic remained the same during pre- and postintervention periods (P
      =.625). The rates of negative interactions per 100 large trucks decreased for
      both large trucks and passenger vehicles after the intervention, with calculated
      rate ratios of 0.58 (95% confidence interval [CI], 0.48, 0.70) and 0.31 (95% CI,
      0.20, 0.47). The greatest reduction was seen in passenger vehicles following too
      close, with a rate ratio of 0.21 (95% CI, 0.15, 0.30). CONCLUSIONS: Although
      designed for reducing crashes on highways, the TACT program can be an effective
      approach for improving driver behaviors on city streets.

PMID- 28750170
TI  - Arpp19 in prophase I resumption.

PMID- 28750171
TI  - Remediation of social communication impairments following traumatic brain injury
      using metacognitive strategy intervention: a pilot study.
AB  - OBJECTIVE: To perform a pilot study to evaluate whether a novel metacognitive,
      goal-based intervention improved and maintained the social communication skills
      of adults with traumatic brain injury (TBI). METHOD: Eight community-dwelling
      participants with TBI completed three study phases: (1) baseline, (2) eight-week
      intervention targeting social communication impairments and (3) follow-up.
      Participants completed the Profile of Pragmatic Impairment in Communication
      (PPIC), LaTrobe Communication Questionnaire (LCQ) and Goal Attainment Scaling
      (GAS) at the commencement of baseline phase, pre- and post-intervention and
      completion of the follow-up phase. During the intervention programme phase,
      participants attended two 1-hour therapy sessions (one individual; one group) per
      week focusing on remediating impaired social communication skills using
      metacognitive strategy intervention and goal-based therapy. RESULTS: Variable
      changes in PPIC feature-summary scores were observed post-intervention. A non
      significant improvement in LCQ scores was also observed. There was a significant
      increase in GAS goal T-scores following the intervention, with six of the eight
      participants achieving or exceeding their expected level of performance on all
      goals. CONCLUSION: A goal-driven, metacognitive approach to intervention may
      assist individuals with TBI to achieve their personal social communication goals,
      with benefits reported by participants and observable during conversations.
      Further research is required.

PMID- 28750172
TI  - Transgenerational modification of hippocampus TNF-alpha and S100B levels in the
      offspring of rats chronically exposed to morphine during adolescence.
AB  - BACKGROUND: TNF-alpha and S100B are important signaling factors that are involved
      in many aberrant conditions of the brain. Chronic morphine exposure causes
      aberrant modifications in the brain. OBJECTIVES: We examined the consequences of
      chronic morphine consumption by parents before mating on hippocampus TNF-alpha
      and S100B levels in the parents and their offspring. METHODS: A total of 12 adult
      female and 12 adult male Wistar rats were used as parents. Each gender was
      divided randomly into two groups: control and morphine consumer. Morphine
      consumer groups received morphine sulfate dissolved in drinking water (0.4 mg/ml)
      for 60 days. Control groups received water. Thirty days before mating, morphine
      was replaced with water. All offspring also received water. The hippocampus of
      both parental and offspring groups was extracted to measure TNF-alpha and S100B
      levels using an ELISA. RESULTS: Hippocampus TNF-alpha levels were significantly
      increased due to chronic morphine use in both male and female parents compared to
      those of control parents (P < 0.01). Moreover, both male and female offspring of
      morphine-exposed parents showed a significant increase in hippocampus TNF-alpha
      levels compared to those of control offspring (P < 0.01). Hippocampus levels of
      S100B were significantly decreased in male (P < 0.05) but not female morphine
      consumer parents relative to control parents. Both male and female offspring of
      morphine-exposed parents showed significant decreases in hippocampus S100B levels
      (P < 0.05) compared to those of control offspring. CONCLUSIONS: The consequences
      of chronic morphine use by parents, even when it is stopped long before mating
      and pregnancy, could induce modifications in the hippocampus of the next
      generation.

PMID- 28750173
TI  - The experiences of parenting a child with an acquired brain injury: A meta
      synthesis of the qualitative literature.
AB  - OBJECTIVE: To systematically review and then synthesize the qualitative
      literature on the experience of parenting a child with an acquired brain injury
      (ABI). DESIGN: Systematic literature review and meta-synthesis Methods. A
      systematic search of the literature was conducted in four databases. Papers which
      met the inclusion criterion were assessed for quality using the Critical Skills
      Appraisal Programme (CASP) tool and then synthesized according to Noblit and
      Hare's (1988) guidelines for meta-ethnography. RESULTS: Of the 4855 papers
      retrieved, 17 met the inclusion criteria. Synthesis resulted in three themes: (1)
      Disconnection: Cut off from internal emotions and isolated from others; (2)
      Seeking understanding and support to manage in an insecure world; and (3) New
      parent to a different child. CONCLUSIONS: Having a child with an ABI leads to
      many challenges for parents. These include feeling insecure, isolated from others
      and struggling to adapt to the different roles required to parent their different
      child. Clinical implications highlight the need for specialist support that is
      ongoing after discharge, including specialist knowledge and understanding of ABI
      and opportunities for peer support.

PMID- 28750174
TI  - Cognitive fatigue: an impaired cortical inhibitory replenishment.
AB  - PRIMARY OBJECTIVE: The present study explores the cause of cognitive fatigue in
      persons with traumatic brain injury (TBI), as also in persons with Multiple
      Sclerosis (MS). Since cognitive fatigue shares many symptoms with chronic sleep
      deprivation (best described as cumulative excess wakefulness), it was
      hypothesized that cognitive fatigue is caused by cumulative excess wakefulness
      because of an impaired sleep efficacy. Recent results about the nature of sleep
      advocate that sleep aims primarily to replenish the efficiency of cortical
      inhibitory synapses. RESEARCH DESIGN: We extensively researched in the TBI and MS
      literature on cognitive fatigue facts that sustained, or invalidate, our
      hypothesis. METHODS AND PROCEDURES: We primary focused on TBI, but cognitive
      fatigue has received much more interest from the MS research community. We
      therefore used results from the MS literature to consolidate our TBI findings.
      MAIN OUTCOMES AND RESULTS: There are objective reasons related to TBI and MS
      disease to suppose that NonREM sleep's efficacy is impaired (despite a normal
      duration of sleep). CONCLUSIONS: Strategies providing a more efficient NonREM
      sleep could demonstrate some therapeutic action against cognitive fatigue.

PMID- 28750175
TI  - Kaposi's sarcoma-associated herpesvirus infection promotes differentiation and
      polarization of monocytes into tumor-associated macrophages.
AB  - Tumor associated macrophages (TAMs) promote angiogenesis, tumor invasion and
      metastasis, and suppression of anti-tumor immunity. These myeloid cells originate
      from monocytes, which differentiate into TAMs upon exposure to the local tumor
      microenvironment. We previously reported that Kaposi's sarcoma-associated herpes
      virus (KSHV) infection of endothelial cells induces the cytokine angiopoietin-2
      (Ang-2) to promote migration of monocytes into tumors. Here we report that KSHV
      infection of endothelial cells induces additional cytokines including interleukin
      6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) that drive monocytes
      to differentiate and polarize into TAMs. The KSHV-induced TAMs not only express
      TAM-specific markers such as CD-163 and legumain (LGMN) but also display a gene
      expression profile with characteristic features of viral infection. More
      importantly, KSHV-induced TAMs enhance tumor growth in nude mice. These results
      are consistent with the strong presence of TAMs in Kaposi's sarcoma (KS) tumors.
      Therefore, KSHV infection of endothelial cells generates a local microenvironment
      that not only promotes the recruitment of monocytes but also induces their
      differentiation and polarization into TAMs. These findings reveal a new mechanism
      of KSHV contribution to KS tumor development.

PMID- 28750176
TI  - Back to America: tracking the origin of European introduced populations of
      Quercus rubra L.
AB  - Quercus rubra has been introduced in Europe since the end of the 17th century. It
      is widely distributed today across this continent and considered invasive in some
      countries. Here, we investigated the distribution of genetic diversity of both
      native and introduced populations with the aim of tracing the origin of
      introduced populations. A large sampling of 883 individuals from 73 native and 38
      European locations were genotyped at 69 SNPs. In the natural range, we found a
      continuous geographic gradient of variation with a predominant latitudinal
      component. We explored the existence of ancestral populations by performing
      Bayesian clustering analysis and found support for two or three ancestral genetic
      clusters. Approximate Bayesian Computations analyses based on these two or three
      clusters support recent extensive secondary contacts between them, suggesting
      that present-day continuous genetic variation resulted from recent admixture. In
      the introduced range, one main genetic cluster was not recovered in Europe,
      suggesting that source populations were preferentially located in the northern
      part of the natural distribution. However, our results cannot refute the
      introduction of populations from the southern states that did not survive in
      Europe.

PMID- 28750177
TI  - Increasing age is a major risk factor for susceptibility to heat stress during
      physical activity.
AB  - We evaluated the extent to which age, cardiorespiratory fitness, and body fat can
      independently determine whole-body heat loss (WBHL) in 87 otherwise healthy
      adults. We show that increasing age is a major predictor for decreasing WBHL in
      otherwise healthy adults (aged 20-70 years), accounting for 40% of the variation
      in the largest study to date. While greater body fat also had a minor detrimental
      impact on WBHL, there was no significant role for cardiorespiratory fitness.

PMID- 28750178
TI  - Modifying an evidence-based lifestyle programme for individuals with traumatic
      brain injury.
AB  - OBJECTIVE: Individuals with traumatic brain injury (TBI) are at a risk of obesity
      related chronic diseases; yet, no evidence-based strategies exist to support
      weight management in this population. The purpose of this study was to use
      participatory action research to modify the Diabetes Prevention Program Group
      Lifestyle Balance (DPP-GLB) programme for overweight/obese people with TBI. The
      DPP-GLB programme provides education and self-management skills for individuals
      to reach their lifestyle goals through healthy eating and physical activity.
      METHODS: A committee of 10 stakeholders including clinicians, patients and
      caregivers reviewed and modified the DPP-GLB for overweight/obese individuals
      with TBI. Stakeholders suggested modifications to the content, layout, format,
      language, behaviour-changing strategies and delivery approaches. The group also
      provided input on research applications of the modified DPP-GLB including
      recruitment strategies, study design and patient-centred outcome measures.
      RESULTS: Strategies for successful implementation in this population focused on
      determining (1) eligibility criteria for programme inclusion and (2) adaptations
      to the DPP-GLB curriculum including caregiver involvement, TBI-specific physical
      activity and nutrition recommendations and tracking and presentation of the
      content. CONCLUSIONS: If it is shown to be effective in this population, the
      modified DPP-GLB for TBI will provide a model for implementation in a variety of
      community settings.

PMID- 28750179
TI  - Effects of propofol on conditioned place preference in male rats: Involvement of
      nitrergic system.
AB  - BACKGROUND: Drug-induced conditioned place preference (CPP) is linked to the
      addictive properties of the drug used. The number of studies that have
      investigated the effects of propofol on CPP is limited. Research findings suggest
      that nitric oxide (NO) might play an important role in substance use disorders.
      OBJECTIVES: The present study sought to investigate the role of the nitrergic
      system on the rewarding effects of propofol by using the CPP protocol in rats.
      METHODS: The experiment followed habituation, pre-conditioning, conditioning, and
      post conditioning sessions. Male Wistar albino rats weighing 240-290 g were
      divided into eight groups: control (saline), propofol (10, 20, and 40 mg/kg), the
      NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) alone (30
      and 60 mg/kg), and in combination with propofol (30 and 60 mg/kg L-NAME plus 40
      mg/kg propofol) (n = 8 for each group). The CPP effects of propofol, L-NAME,
      saline, and their combinations were evaluated. All the drug and saline
      administrations were performed by intraperitoneal (ip) injections. RESULTS:
      Propofol (10-40 mg/kg) produced CPP that was statistically significant relative
      to saline. Propofol-induced CPP was significantly reversed by pretreatment with L
      NAME. When administered alone, L-NAME did not produce CPP and also did not
      produce any significant change on locomotor activity of naive rats. CONCLUSION:
      Our results suggest that propofol produces CPP effects in rats and that NO
      related mechanisms may be responsible for propofol-induced CPP. Thus, propofol
      might have the potential to be addictive, and this possibility should be
      considered during clinical applications of this drug.

PMID- 28750180
TI  - Association between inspiratory muscle weakness and slowed oxygen uptake kinetics
      in patients with chronic obstructive pulmonary disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) may have poor
      inspiratory muscle function, which reduces minute and alveolar ventilation,
      leading to increased hypoxemia and slow pulmonary oxygen uptake kinetics.
      However, little is known about the effect of inspiratory muscle weakness (IMW) on
      oxygen uptake kinetics in patients with COPD. Thus, we tested the hypothesis that
      COPD patients with IMW have slowed oxygen uptake kinetics. An observational study
      was conducted that included COPD patients with moderate to severe airflow
      limitation and a history of intolerance to exercise. Participants were divided
      into 2 groups: (IMW+; n = 22) (IMW-; n = 23) of muscle weakness. The maximal
      inspiratory, expiratory, and sustained inspiratory strength as well as the
      maximal endurance of the inspiratory muscles were lower in IMW+ patients (36 +/-
      9.5 cm H2O; 52 +/- 14 cm H2O; 20 +/- 6.5 cm H2O; 94 +/- 84 s, respectively) than
      in IMW- patients (88 +/- 12 cm H2O; 97 +/- 28 cm H2O; 82.5 +/- 54 cm H2O; 559 +/-
      92 s, respectively; p < 0.05). Moreover, the 6-min walk test and peak oxygen
      uptake were reduced in the IMW+ patients. During the constant work test, oxygen
      uptake kinetics were slowed in the IMW+ compared with IMW- patients (88 +/- 29 vs
      61 +/- 18 s, p < 0.05). Our findings demonstrate that inspiratory muscle weakness
      in COPD is associated with slowed oxygen uptake kinetics, and thus, reduced
      functional capacity.

PMID- 28750181
TI  - SIRT-1 regulates TGF-beta-induced dermal fibroblast migration via modulation of
      Cyr61 expression.
AB  - SIRT1 is a NAD-dependent protein deacetylase that participates in cellular
      regulation. The increased migration of fibroblasts is an important phenotype in
      fibroblast activation. The role of SIRT1 in cell migration remains controversial
      as to whether SIRT1 acts as an activator or suppressor of cell migration.
      Therefore, we have established the role of SIRT1 in the migration of human dermal
      fibroblasts and explored targets of SIRT1 during dermal fibroblast migration.
      SIRT1 and Cyr61 were expressed in human dermal fibroblasts and the stimulation
      with TGF-beta further induced their expression. Treatment with resveratrol (RSV),
      a SIRT1 agonist, or overexpression of SIRT1 also promoted the expression Cyr61 in
      human dermal fibroblasts, whereas the inhibition of SIRT1 activity by
      nicotinamide or knockdown of SIRT1 decreased the level of Cyr61, as well as TGF
      beta or RSV-induced Cyr61 expression. Blocking of ERK signaling by PD98509
      reduced the expression of Cyr61 induced by TGF-beta or RSV. TGF-beta, RSV, or
      SIRT1 overexpression enhanced beta-catenin as well as Cyr61 expression. This
      stimulation was reduced by the Wnt inhibitor XAV939. RSV increased migration and
      nicotinamide attenuated RSV-induced migration of human dermal fibroblasts.
      Furthermore, SIRT1 overexpression promoted cell migration, whereas blocking Cyr61
      attenuated SIRT1-stimulated migration of human dermal fibroblasts. SIRT1
      increased cell migration by stimulating Cyr61 expression and the ERK and Wnt/beta
      catenin signaling. SIRT1-induced Cyr61 activity is very important for human
      dermal fibroblasts migration.

PMID- 28750182
TI  - Subacute sclerosing panencephalitis should be eliminated by measles vaccination.
AB  - 1 patient with SSPE at 4 y. He had had measles and measles encephalitis at 7.5
      months. In China, the first and the second measles immunizations are recommended
      at 8 months and at 18-24 months, respectively. We recommend above immunizations
      should be given separately at 6 months and at 12-15 months.

PMID- 28750183
TI  - Errata.

PMID- 28750184
TI  - Errata.

PMID- 28750185
TI  - Errata.

PMID- 28750186
TI  - Errata.

PMID- 28750187
TI  - Errata.

PMID- 28750188
TI  - Errata.

PMID- 28750189
TI  - Potential markers and metabolic processes involved in the mechanism of radiation
      induced heart injury.
AB  - Irradiation of normal tissues leads to acute increase in reactive oxygen/nitrogen
      species that serve as intra- and inter-cellular signaling to alter cell and
      tissue function. In the case of chest irradiation, it can affect the heart, blood
      vessels, and lungs, with consequent tissue remodelation and adverse side effects
      and symptoms. This complex process is orchestrated by a large number of
      interacting molecular signals, including cytokines, chemokines, and growth
      factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ
      dysfunction, and ultimate failing of the heart occur as a pathological entity -
      "radiation-induced heart disease" (RIHD) that is major source of morbidity and
      mortality. The purpose of this review is to bring insights into the basic
      mechanisms of RIHD that may lead to the identification of targets for
      intervention in the radiotherapy side effect. Studies of authors also provide
      knowledge about how to select targeted drugs or biological molecules to modify
      the progression of radiation damage in the heart. New prospective studies are
      needed to validate that assessed factors and changes are useful as early markers
      of cardiac damage.

PMID- 28750190
TI  - Design and Characterization of a Soft Robotic Therapeutic Glove for Rheumatoid
      Arthritis.
AB  - The modeling and experimentation of a pneumatic actuation system for the
      development of a soft robotic therapeutic glove is proposed in this article for
      the prevention of finger deformities in rheumatoid arthritis (RA) patients. The
      Rehabilitative Arthritis Glove (RA-Glove) is a soft robotic glove fitted with two
      internal inflatable actuators for lateral compression and massage of the fingers
      and their joints. Two mechanical models to predict the indentation and bending
      characteristics of the inflatable actuators based on their geometrical parameters
      will be presented and validated with experimental results. Experimental
      validation shows that the model was within a standard deviation of the
      experimental mean for input pressure range of 0 to 2 bars. Evaluation of the RA
      Glove was also performed on six healthy human subjects. The stress distribution
      along the fingers of the subjects using the RA-Glove was also shown to be even
      and specific to the finger sizes. This article demonstrates the modeling of soft
      pneumatic actuators and highlights the potential of the RA-Glove as a therapeutic
      device for the prevention of arthritic deformities of the fingers.

PMID- 28750191
TI  - Classification of Upper Body Shapes Among Korean Male Wheelchair Users to Improve
      Clothing Fit.
AB  - The upper body shape is an important factor to be considered in customized suit
      jacket design. The present study is intended to identify the lateral upper body
      shapes of wheelchair users in a sagittal plane. Anthropometric data of 144 Korean
      male wheelchair users were collected using a tape measure and photography. Three
      lateral upper body shapes were identified by cluster analysis: convex back with
      largely protruded abdomen (31%), convex back with flat abdomen (36%), and
      straight back with moderately protruded abdomen (33%). Discriminant functions
      were constructed for the three lateral upper body shape groups, and their overall
      and cross-validated classification accuracies were identified as 94.4% and 89.6%,
      respectively. The present study found that the wheelchair users have more convex
      back (67%) and protruded abdomen (64%) shapes than non-wheelchair individuals.
      The lateral upper body shapes and discriminant functions identified in the study
      can be applied to a custom production process of suit jacket design for
      wheelchair users.

PMID- 28750192
TI  - Comprehensive, technology-based, team approach for a patient with locked-in
      syndrome: A case report of improved function & quality of life.
AB  - One of the most severe types of stroke is locked-in syndrome (LIS) due to the
      loss of almost all voluntary motor functions and a high mortality rate. The
      majority of the literature regarding LIS is based on case reports that utilized
      multidisciplinary interventions focused on improving functional communication and
      respiratory care with minimal focus on motor retraining. These reports were
      neither dynamic nor multi-sensory, and the only technology utilized was in the
      form of augmentative communication. There are additional types of technology
      frequently used in the general stroke population that can address similar motor
      deficits that occur in the LIS population. This case report explains an
      interdisciplinary approach using motor and communication interventions that are
      multisensory, progressive, multi-modal, and technology- based. The length of stay
      was 153 days in acute rehabilitation, after which the patient returned home
      making significant gains in overall function. In this patient, the FIM changes in
      motor (+42), cognitive (+29) and total change score of (+71) surpassed what was
      determined to be a minimal clinically important difference. These results suggest
      that this treatment program and approach may be a key reason why this patient was
      able to achieve significant functional gains and report improved quality of life.

PMID- 28750193
TI  - Awareness, Possession, and Use of Take-Home Naloxone Among Illicit Drug Users,
      Vancouver, British Columbia, 2014-2015.
AB  - OBJECTIVES: Although take-home naloxone (THN) programs are integral in strategies
      to prevent overdose deaths among opioid users, the uptake of THN among people who
      use drugs (PWUD) (including non-opioid users) is unknown. The objectives of this
      study were to determine awareness, possession, and use of THN among PWUD in
      Vancouver, Canada, and identify barriers to adopting this strategy. METHODS: From
      December 1, 2014, to May 29, 2015, participants in 2 prospective cohort studies
      of PWUD in Vancouver completed a standardized questionnaire, which asked about
      awareness, possession, and use of THN; sociodemographic characteristics; and drug
      use patterns. We conducted multivariable logistic regression analyses to
      determine factors independently associated with awareness and possession of THN.
      RESULTS: Of 1137 PWUD, 727 (64%) reported at least 1 previous overdose ever, and
      220 (19%) had witnessed an overdose in the previous 6 months. Although 769 (68%)
      participants overall reported awareness of THN, only 88 of 392 (22%) opioid users
      had a THN kit, 18 (20%) of whom had previously administered naloxone. Factors
      that were positively associated with awareness of THN included witnessing an
      overdose in the previous 6 months (adjusted odds ratio [aOR] = 2.23; 95%
      confidence interval [CI], 1.49-3.34; P < .001), possession of THN (aOR = 1.85;
      95% CI, 1.11-3.06; P = .02), younger age (aOR = 1.02; 95% CI, 1.01-1.04; P =
      .003), white race (aOR = 1.67; 95% CI, 1.27-2.19; P < .001), hepatitis C
      infection (aOR = 1.63; 95% CI, 1.13-2.36; P = .01), residing in Vancouver's
      Downtown Eastside neighborhood (aOR = 1.93; 95% CI, 1.47-2.53; P < .001), and at
      least daily heroin injection (aOR = 1.69; 95% CI, 1.09-2.62; P < .02).
      CONCLUSION: Efforts to improve knowledge of and participation in the THN program
      may contribute to reduced opioid overdose mortality in Vancouver.

PMID- 28750195
TI  - New Isn't Everything.

PMID- 28750194
TI  - Ketoacidosis alone does not predispose to mucormycosis by Lichtheimia in a murine
      pulmonary infection model.
AB  - Mucormycosis is a rare fungal infection; however, the number of cases increased
      during the last decades. The main risk factors are immunosuppression and
      uncontrolled diabetes mellitus. Although Lichtheimia species represent a common
      cause of mucormycosis in Europe, virulence and pathogenesis of this genus has not
      been investigated in detail yet. Using murine pulmonary infection models, we
      found that immunosuppression is essential for establishment of infection. The
      disease was characterized by necrosis, angioinvasion, thrombosis, and the lethal
      course of infection was associated with systemic activation of platelets.
      Furthermore, dissemination to internal organs was frequently observed. While the
      virulence potential of individual L. corymbifera and L. ramosa isolates differed,
      pathogenicity of both species was comparable. Although ketoacidosis promoted
      Rhizopus infection in mice, it did not predispose mice to infection with
      Lichtheimia in the absence of additional immunosuppression. This might partially
      explain the dominance of Rhizopus as cause of mucormycosis in countries with high
      prevalence of ketoacidotic patients.

PMID- 28750196
TI  - Principles of Systems Biology, No. 19.
AB  - This month: building bacterial organelles (Kerfeld, Tullman-Ercek), the widening
      scope of single cell analysis (Takebe, Glass, Rabadan), insights from yeast
      (Swain, Dunham), and more (Bloom, Romesberg, Gibson).

PMID- 28750197
TI  - Systematic Investigation of Multi-TLR Sensing Identifies Regulators of Sustained
      Gene Activation in Macrophages.
AB  - A typical pathogen presents a combination of Toll-like receptor (TLR) ligands
      during infection. Although individual TLR pathways have been well characterized,
      the nature of this "combinatorial code" in pathogen sensing remains unclear.
      Here, we conducted a comprehensive transcriptomic analysis of primary macrophages
      stimulated with all possible pairwise combinations of four different TLR ligands
      to understand the requirements, kinetics, and outcome of combined pathway
      engagement. We find that signal integration between TLR pathways leads to non
      additive responses for a subset of immune mediators with sustained expression (>6
      hr) properties and T cell polarizing function. To identify the underlying
      regulators, we conducted a focused RNAi screen and identified four genes-Helz2,
      Phf11d, Sertad3, and Zscan12-which preferentially affect the late phase response
      of TLR-induced immune effector expression. This study reveals key molecular
      details of how contemporaneous signaling through multiple TLRs, as would often be
      the case with pathogen infection, produce biological outcomes distinct from the
      single ligands typically used to characterize TLR pathways.

PMID- 28750198
TI  - High-Resolution Laser Scanning Reveals Plant Architectures that Reflect Universal
      Network Design Principles.
AB  - Transport networks serve critical functions in biological and engineered systems,
      and yet their design requires trade-offs between competing objectives. Due to
      their sessile lifestyle, plants need to optimize their architecture to
      efficiently acquire and distribute resources while also minimizing costs in
      building infrastructure. To understand how plants resolve this design trade-off,
      we used high-precision three-dimensional laser scanning to map the architectures
      of tomato, tobacco, or sorghum plants grown in several environmental conditions
      and through multiple developmental time points, scanning in total 505
      architectures from 37 plants. Using a graph-theoretic algorithm that we developed
      to evaluate design strategies, we find that plant architectures lie along the
      Pareto front between two simple length-based objectives-minimizing total branch
      length and minimizing nutrient transport distance-thereby conferring a selective
      fitness advantage for plant transport processes. The location along the Pareto
      front can distinguish among species and conditions, suggesting that during
      evolution, natural selection may employ common network design principles despite
      different optimization trade-offs.

PMID- 28750199
TI  - A Systems Approach to Healthcare Innovation Using the MIT Hacking Medicine Model.
AB  - MIT Hacking Medicine is a student, academic, and community-led organization that
      uses systems-oriented "healthcare hacking" to address challenges around
      innovation in healthcare. The group has organized more than 80 events around the
      world that attract participants with diverse backgrounds. These participants are
      trained to address clinical needs from the perspective of multiple stakeholders
      and emphasize utility and implementation viability of proposed solutions. We
      describe the MIT Hacking Medicine model as a potential method to integrate
      collaboration and training in rapid innovation techniques into academic medical
      centers. Built upon a systems approach to healthcare innovation, the time
      compressed but expertly guided nature of the events could enable more widely
      accessible preliminary training in systems-level innovation methodology, as well
      as creating a structured opportunity for interdisciplinary congregation and
      collaboration.

PMID- 28750200
TI  - Incoherent Inputs Enhance the Robustness of Biological Oscillators.
AB  - Robust biological oscillators retain the critical ability to function in the
      presence of environmental perturbations. Although central architectures that
      support robust oscillations have been extensively studied, networks containing
      the same core vary drastically in their potential to oscillate, and it remains
      elusive what peripheral modifications to the core contribute to this functional
      variation. Here, we have generated a complete atlas of two- and three-node
      oscillators computationally, then systematically analyzed the association between
      network structure and robustness. We found that, while certain core topologies
      are essential for producing a robust oscillator, local structures can
      substantially modulate the robustness of oscillations. Notably, local nodes
      receiving incoherent or coherent inputs respectively promote or attenuate the
      overall network robustness in an additive manner. We validated these
      relationships in larger-scale networks reflective of real biological oscillators.
      Our findings provide an explanation for why auxiliary structures not required for
      oscillation are evolutionarily conserved and suggest simple ways to evolve or
      design robust oscillators.

PMID- 28750201
TI  - Advancing therapeutic applications of synthetic gene circuits.
AB  - Synthetic biology aims to introduce new sense-and-respond capabilities into
      living cells, which would enable novel therapeutic strategies. The development of
      regulatory elements, molecular computing devices, and effector screening
      technologies has enabled researchers to design synthetic gene circuits in many
      organisms, including mammalian cells. Engineered gene networks, such as closed
      loop circuits or Boolean logic gate circuits, can be used to program cells to
      perform specific functions with spatiotemporal control and restoration of
      homeostasis in response to the extracellular environment and intracellular
      signaling. In addition, genetically modified microbes can be designed as local
      delivery of therapeutic molecules. In this review, we will discuss recent
      advances in therapeutic applications of synthetic gene circuits, as well as
      challenges and future opportunities for biomedicine.

PMID- 28750202
TI  - Combinatorial pathway optimization for streamlined metabolic engineering.
AB  - Elimination of metabolic flux imbalances in microbial cell factories is an
      important part in the establishment of viable biotechnological production
      processes. However, due to the high complexity of cellular metabolism, the
      limited a priori knowledge about the majority of production pathways and a lack
      of forward design standards, metabolic engineers strongly rely on empirical
      screening methodologies to achieve the required improvement of cell behavior.
      Combinatorial pathway engineering provides an interesting tool to identify global
      solutions for intricate pathways, but methods for the reduction of combinatorial
      library size are inevitably required to restrict the experimental effort to an
      affordable size. Here we review recent advances from this field by scrutinizing
      commonly applied diversification methods and highlighting crucial strategies for
      the minimization of experimental effort.

PMID- 28750203
TI  - Synthesis, alpha-glucosidase inhibitory activity and in silico study of tris
      indole hybrid scaffold with oxadiazole ring: As potential leads for the
      management of type-II diabetes mellitus.
AB  - Discovery of alpha-glucosidase inhibitors has been actively pursued with the aim
      to develop therapeutics for the treatment of type-II diabetes mellitus and the
      other carbohydrate mediated disease. In continuation of our drug discovery
      research on potential antidiabetic agents, we synthesized novel tris-indole
      oxadiazole hybrid analogs (1-21), structurally characterized by various
      spectroscopic techniques such as 1H NMR, EI-MS, and 13C NMR. Elemental analysis
      was found in agreement with the calculated values. All compounds were evaluated
      for alpha-glucosidase inhibiting potential and showed potent inhibitory activity
      in the range of IC50=2.00+/-0.01-292.40+/-3.16MUM as compared to standard
      acarbose (IC50=895.09+/-2.04uM). The pharmacokinetic predictions of tris-indole
      series using descriptor properties showed that almost all compounds in this
      series indicate the drug aptness. Detailed binding mode analyses with docking
      simulation was also carried out which showed that the inhibitors can be
      stabilized by the formation of hydrogen bonds with catalytic residues and the
      establishment of hydrophobic contacts at the opposite side of the active site.

PMID- 28750204
TI  - Synthesis and anticancer activity of new thiazolo[3,2-a]pyrimidines: DNA binding
      and molecular modeling study.
AB  - A novel series of nitrogenous heterocycles starting from chalcones including
      thiazolo[3,2-a]pyrimidines (20-67), were synthesized. Structure elucidation of
      the synthesized compounds was attained by the use of 1H NMR, 13CC NMR, and Mass
      spectrometry. The obtained compounds were evaluated for their in vitro anticancer
      activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Three
      cell lines, non-small cell lung cancer Hop-92, ovarian cancer IGROV1, and
      melanoma SK-MEL-2, exhibited some sensitivity against most of the tested
      compounds. Six compounds have passed the 5-log dose level NCI assay. Compounds 34
      and 24 proved to be the most active derivatives with GI50, TGI, LC50 of 5.89,
      20.0, 66.1% and 5.0, 19.5, 52.5% respectively. Compounds 36, 39, 63 showed lesser
      activity with GI50, TGI, LC50 3.2, 11.8, 38.9%, 3.4, 16.6, 60.3%, 3.5, 17.8,
      66.1% respectively. DNA binding assay of synthesized compound were performed.
      Molecular docking showed that compounds 34, 42, and 60 could effectively fit into
      the minor groove and selectively bind with AT base pairs. The results could
      confer the anticancer activity of compounds 24, 34, 36, and 39in vitro to their
      abilities to bind at DNA minor groove.

PMID- 28750205
TI  - Corrigendum to "The physical mechanism of "inhomogeneous" magnetization transfer
      MRI" [J. Magn. Reson. 274 (2017) 125-136].

PMID- 28750206
TI  - Plant mechanosensitive ion channels: an ocean of possibilities.
AB  - Mechanosensitive ion channels, transmembrane proteins that directly couple
      mechanical stimuli to ion flux, serve to sense and respond to changes in membrane
      tension in all branches of life. In plants, mechanosensitive channels have been
      implicated in the perception of important mechanical stimuli such as osmotic
      pressure, touch, gravity, and pathogenic invasion. Indeed, three established
      families of plant mechanosensitive ion channels play roles in cell and organelle
      osmoregulation and root mechanosensing - and it is likely that many other
      channels and functions await discovery. Inspired by recent discoveries in
      bacterial and animal systems, we are beginning to establish the conserved and the
      unique ways in which mechanosensitive channels function in plants.

PMID- 28750207
TI  - Eye gaze and pupillary response in Angelman syndrome.
AB  - BACKGROUND: Angelman syndrome (AS) is a rare neurological disorder characterized
      by severe developmental disability, communication impairment, elevated seizure
      risk, and motor system abnormalities. AIMS: The aims of this study were to
      determine the feasibility of social scene eye tracking and pupillometry measures
      in individuals with AS and to compare the performance of AS participants to
      individuals with idiopathic Autism Spectrum Disorder (ASD) and typically
      developing controls (TDC). METHODS AND PROCEDURES: Individuals with AS and age-
      and gender- matched controls completed a social eye tracking paradigm.
      Neurobehavioral characterization of AS participants was completed via a battery
      of psychological testing and caregiver behavioral evaluations. OUTCOMES AND
      RESULTS: Eight of seventeen recruited AS participants completed the eye tracking
      paradigm. Compared to TDC, AS subjects demonstrated significantly less preference
      for social scenes than geometric shapes. Additionally, AS subjects showed less
      pupil dilation, compared to TDC, when viewing social scenes versus geometric
      shapes. There was no statistically significant difference found between AS and
      ASD subjects in either social eye tracking or pupillometry. CONCLUSIONS AND
      IMPLICATIONS: The use of eye tracking and pupillometry may represent an
      innovative measure for quantifying AS-associated impairments in social salience.

PMID- 28750208
TI  - Understanding low levels of physical activity in people with intellectual
      disabilities: A systematic review to identify barriers and facilitators.
AB  - BACKGROUND: People with intellectual disabilities (ID) undertake extremely low
      levels of physical activity. AIMS: To enhance understanding concerning low levels
      of physical activity in people with ID, this study has three aims: (1) to
      identify barriers to and facilitators of physical activity in people with ID; (2)
      to examine differences in barriers and facilitators between levels of ID (mild,
      moderate, severe, and profound); (3) to examine differences in barriers and
      facilitators between various stakeholder groups. METHODS AND PROCEDURES: A
      systematic search was performed using the following databases from the year 1990:
      MEDLINE, ERIC, and PsycINFO. The studies included were peer reviewed, available
      as full text, and written in English, addressing barriers to and facilitators of
      physical activity in people with ID. The quality of the studies was assessed
      using existing critical review forms. All studies were subjected to qualitative
      synthesis to identify and compare barriers and facilitators. OUTCOMES AND
      RESULTS: In all, 24 studies were retrieved, describing 14 personal and 23
      environmental barriers and/or facilitators. The quality of the studies varied,
      particularly for qualitative studies. Only two studies included people with
      severe or profound ID. Stakeholder groups tend to identify barriers outside their
      own responsibility. CONCLUSIONS AND IMPLICATIONS: Results reveal a broad range of
      barriers and facilitators, but not for people with more severe ID. Further
      research should also examine these factors among stakeholders responsible for
      providing support.

PMID- 28750209
TI  - The listener automatically uses spatial story representations from the speaker's
      cohesive gestures when processing subsequent sentences without gestures.
AB  - This study examined spatial story representations created by speaker's cohesive
      gestures. Participants were presented with three-sentence discourse with two
      protagonists. In the first and second sentences, gestures consistently located
      the two protagonists in the gesture space: one to the right and the other to the
      left. The third sentence (without gestures) referred to one of the protagonists,
      and the participants responded with one of the two keys to indicate the relevant
      protagonist. The response keys were either spatially congruent or incongruent
      with the gesturally established locations for the two participants. Though the
      cohesive gestures did not provide any clue for the correct response, they
      influenced performance: the reaction time in the congruent condition was faster
      than that in the incongruent condition. Thus, cohesive gestures automatically
      establish spatial story representations and the spatial story representations
      remain activated in a subsequent sentence without any gesture.

PMID- 28750210
TI  - Phosphorylated neurofilament H (pNF-H) as a potential diagnostic marker for
      neurological disorders in horses.
AB  - The current study aimed at the investigating the potential use of phosphorylated
      neurofilament H (pNF-H) as a diagnostic biomarker for neurologic disorders in the
      horse. Paired serum and cerebrospinal fluid (CSF) samples (n=88) and serum only
      (n=30) were obtained from horses diagnosed with neurologic disorders and
      clinically healthy horses as control. The neurologic horses consisted of equine
      protozoal myeloencephalitis (EPM) (38 cases) and cervical vertebral malformation
      (CVM) (23 cases). Levels of pNF-H were determined using an ELISA. The correlation
      between CSF and serum concentrations of pNF-H was evaluated using Spearman's Rank
      test and the significance of the difference among the groups was assessed using a
      nonparametric test. Horses had higher pNF-H levels in the CSF than serum. Horses
      afflicted with EPM had significantly higher serum pNF-H levels in comparison to
      controls or CVM cases. The correlation between CSF and serum pNF-H levels was
      poor in both the whole study population and among subgroups of horses included in
      the study. There was significant association between the likelihood of EPM and
      the concentrations of pNF-H in either the serum or CSF. These data suggest that
      pNF-H could be detected in serum and CSF samples from neurologic and control
      horses. This study demonstrated that pNF-H levels in serum and CSF have the
      potential to provide objective information to help in the early diagnosis of
      horses afflicted with neurologic disorders.

PMID- 28750211
TI  - Moxidectin residues in tissues of lambs submitted to three endoparasite control
      programs.
AB  - The indiscriminate and continuous use of anthelmintic drugs has promoted the
      selection of resistant parasites population, the presence of drug residues in
      food products, and heavy environmental contamination. The aim of the present
      study was to determine the presence of antiparasitic drug residues in 42-days old
      lamb serum and tissues, submitted to three endoparasite control programs:
      preventive treatment (PT) using moxidectin (MOX) at every 28days; selective
      treatment (FEC) using MOX when fecal egg count was greater than or equal to 700;
      and selective treatment (FMC), using MOX when FAMACHA/FMC score was 3 and above.
      For this purpose, MOX residues were quantified in serum, muscle, fat, liver and
      kidney. Lambs were slaughtered when reaching 30kg of body weight, and after a 28
      day MOX withdrawal period. Before slaughter, blood was collected to determine the
      concentration of MOX in serum. Tissues and organ samples were collected at
      slaughter. The quantitation of MOX residues was performed using liquid
      chromatography tandem mass spectrometry (LC-MS/MS). From the 756 tissue samples
      analyzed, only one sample of fat from the PT group showed residue levels
      (586.3MUg/kg) above the maximum residue limit (MRL) of 500MUg/kg. No treated
      lambs presented traces of MOX residues in fat and liver, suggesting possible
      environmental contamination. In conclusion, all weaned lambs, produced in
      continuous grazing and subjected to gastrointestinal parasite control programs
      via selective (FEC and FMC) or preventive (PT) treatment, displayed a low risk
      (<1%) of MOX residues above the MRL in muscle, fat, kidney, and liver.

PMID- 28750212
TI  - Cortisol concentration of regrown hair and hair from a previously unshorn area in
      dairy cows.
AB  - This study determined cortisol concentrations in hair that had grown for one
      month and in hair from a previously unshorn area and examined the effects of
      calendar month, pregnancy and illness on hair cortisol concentrations in dairy
      cows. The study was conducted over a one-year period using 27 cows. Electric
      clippers were used to collect two hair samples per cow each month. The first
      sample (A sample) consisted of hair that had grown for one month in a pre-clipped
      area and the second sample (B sample) comprised all hair from a previously
      unshorn area. Liquid chromatography tandem mass-spectrometry was used for
      cortisol measurement. The overall mean concentrations for A and B samples did not
      differ. Cortisol concentrations of A samples were significantly higher in the
      winter (0.86+/-0.37pg/mg) than in the fall (0.67+/-0.33pg/mg). The hair cortisol
      concentration in A samples increased during pregnancy and the maximum
      concentration of 1.40+/-1.08pg/mg hair in the month of calving was significantly
      higher than the concentration measured in the first month (0.66+/-0.32pg/mg). The
      findings show that the effect of short-term stressors such as parturition on hair
      cortisol concentrations are more easily detected in hair that has grown for one
      month than in hair from a previously unshorn area.

PMID- 28750214
TI  - Childhood trauma is not a confounder of the overlap between autistic and
      schizotypal traits: A study in a non-clinical adult sample.
AB  - Childhood trauma has been shown to be a robust risk factor for mental disorders,
      and may exacerbate schizotypal traits or contribute to autistic trait severity.
      However, little is known whether childhood trauma confounds the overlap between
      schizotypal traits and autistic traits. This study examined whether childhood
      trauma acts as a confounding variable in the overlap between autistic and
      schizotypal traits in a large non-clinical adult sample. A total of 2469
      participants completed the Autism Spectrum Quotient (AQ), the Schizotypal
      Personality Questionnaire (SPQ), and the Childhood Trauma Questionnaire-Short
      Form. Correlation analysis showed that the majority of associations between AQ
      variables and SPQ variables were significant (p < 0.05). In the multiple
      regression models predicting scores on the AQ total, scores on the three SPQ
      subscales were significant predictors(Ps < 0.05). Scores on the Positive
      schizotypy and Negative schizotypy subscales were significant predictors in the
      multiple regression model predicting scores on the AQ Social Skill, AQ Attention
      Switching, AQ Attention to Detail, AQ Communication, and AQ Imagination
      subscales. The association between autistic and schizotypal traits could not be
      explained by shared variance in terms of exposure to childhood trauma. The
      findings point to important overlaps in the conceptualization of ASD and SSD,
      independent of childhood trauma.

PMID- 28750213
TI  - Maternal infection and stress during pregnancy and depressive symptoms in
      adolescent offspring.
AB  - Maternal infection during pregnancy has been linked to increased risk of
      offspring depression. Additionally, maternal stress during pregnancy has been
      consistently linked with adverse offspring outcomes associated with depression.
      Relatedly, stress has been associated with increased risk of infection; however
      no study has investigated stress-infection interactions during pregnancy and risk
      for offspring depression. Participants were drawn from the Child Health and
      Development Studies (CHDS), a prospective, longitudinal study that enrolled
      pregnant women from 1959 to 1966. Maternal health and birth outcome information
      were collected, as well as open-ended interviews about worrisome events during
      pregnancy. The present study included participants from a subsample of women
      whose offspring (n = 1711) completed self-reports of depressive symptoms during
      adolescence. Results indicated that maternal infection during only the second
      trimester was associated with higher scores on adolescent offspring depressive
      symptoms, while controlling for maternal education at birth, adolescent age, and
      maternal depressive symptoms at adolescence. Maternal experiences of daily stress
      during pregnancy moderated this association, such that mothers diagnosed with
      second trimester infection and who experienced daily stress had offspring with
      significantly higher depression scores than mothers of adolescents diagnosed with
      an infection alone. Findings have potential implications for prevention and
      intervention strategies.

PMID- 28750215
TI  - Binge-pattern cocaine administration causes long-lasting behavioral hyperarousal
      but does not enhance vulnerability to single prolonged stress in rats.
AB  - Cocaine use disorder and post-traumatic stress disorder (PTSD) commonly co-occur.
      This could be due to vulnerability to post-traumatic symptoms conferred by
      previous exposure to cocaine. Therefore, we combined chronic binge-pattern
      cocaine with a model of psychological trauma (single prolonged stress) to
      determine whether the behavioral effects of psychological trauma are enhanced in
      cocaine-sensitized individuals. Adult male Sprague Dawley rats received 14 days
      of cocaine (15mg/kg/injection) or saline in a binge pattern (3 injections per
      day, 1h apart). Seven days after the last injection animals were exposed to
      traumatic stress or a control procedure. Seven days after stress, activity and
      anxiety-like behaviors were measured. Binge-pattern cocaine increased locomotor
      activity in the open field and elevated plus maze, and both cocaine and SPS
      exposure increased the rapidity with which rats moved through grooming sequences.
      Neither binge-pattern cocaine nor SPS increased anxiety-like behaviors, and no
      interactions were found between binge-pattern cocaine exposure and SPS exposure.
      A behavioral phenotype categorization approach demonstrated that cocaine-exposed
      groups expressed a high incidence of hyperactivity-like symptoms. These results
      suggest that binge-pattern cocaine exposure causes a long-lasting hyper
      exploratory phenotype but does not make individuals more vulnerable to a later
      traumatic stress exposure.

PMID- 28750216
TI  - Efficacy of low carbohydrate diet for type 2 diabetes mellitus management: A
      systematic review and meta-analysis of randomized controlled trials.
AB  - AIMS: The objective of this systematic review and meta-analysis is to assess the
      efficacy of Low Carbohydrate Diet (LCD) compared with a normal or high
      carbohydrate diet in patients with type 2 diabetes. METHODS: We searched MEDLINE,
      EMBASE, and Cochrane Library database for randomized controlled trials.
      Researches which reported the change in weight loss, blood glucose, and blood
      lipid levels were included. RESULTS: A total of 9 studies with 734 patients with
      diabetes were included. Pooled results suggested that LCD had a significantly
      effect on HbA1c level (WMD: -0.44; 95% CI: -0.61, -0.26; P=0.00). For
      cardiovascular risk factors, the LCD intervention significantly reduced
      triglycerides concentration (WMD: -0.33; 95% CI: -0.45, -0.21; P=0.00) and
      increased HDL cholesterol concentration (WMD: 0.07; 95% CI: 0.03, 0.11; P=0.00).
      But the LCD was not associated with decreased level of total cholesterol and LDL
      cholesterol. Subgroup analyses indicated that short term intervention of LCD was
      effective for weight loss (WMD: -1.18; 95% CI: -2.32, -0.04; P=0.04).
      CONCLUSIONS: The results suggested a beneficial effect of LCD intervention on
      glucose control in patients with type 2 diabetes. The LCD intervention also had a
      positive effect on triglycerides and HDL cholesterol concentrations, but without
      significant effect on long term weight loss.

PMID- 28750217
TI  - Association of HSD11B1 gene polymorphisms with type 2 diabetes and metabolic
      syndrome in South Indian population.
AB  - BACKGROUND: 11beta-hydroxysteroid dehydrogenase Type 1 (11beta-HSD1) is an NADP
      or NADPH-dependent enzyme that generates cortisol from cortisone for a local
      glucocorticoid action. Functional polymorphisms within 11beta-hydroxysteroid
      dehydrogenase Type 1 (HSD11B1) gene have shown an association with various
      factors, including insulin resistance (IR) and hypertension. In our study, we
      have assessed the association of HSD11B1 (rs12086634 and rs846910) gene
      polymorphisms with type 2 diabetes (T2D) and metabolic syndrome (metS). METHODS:
      In the present study, 616 subjects were enrolled. DNA from T2D subjects (n=207),
      metS subjects (n=101), and their age and sex matched control subjects were
      analyzed. Genotyping of HSD11B1 rs12086634 and rs846910 single nucleotide
      polymorphisms was performed using tetra-primer amplification refractory mutation
      system-polymerase chain reaction (T-ARMS-PCR). An odds ratio and 95% confidence
      interval were calculated to determine the association of HSD11B1 gene
      polymorphisms with T2D and metS. RESULTS: The association analysis indicated that
      HSD11B1 rs12086634 TG contributed to an increased risk of both T2D (OR=1.91; 95%
      CI-1.33-2.76, P=0.0005) and metS (OR=2.37; 95% CI-1.39-4.05, P=0.0015), but
      HSD11B1 rs846910 AG contributed to an increased risk of T2D (OR=1.62; 95% CI-1.02
      2.57, P=0.03) only. There was a statistically significant difference in systolic
      blood pressure between the control group with HSD11B1 rs12086634 TG genotype
      (128.96+/-13.19mmHg) and the control group with HSD11B1 rs12086634 TT genotype
      (123.27+/-10.84mmHg). CONCLUSIONS: The results of our study indicated that the
      HSD11B1 rs12086634 is associated with both T2D and metS, but HSD11B1 rs846910 is
      associated with only T2D in South Indian population.

PMID- 28750218
TI  - Insulin resistance correlates with maculopathy and severity of retinopathy in
      young adults with Type 1 Diabetes Mellitus.
AB  - AIMS: To assess the relationship between insulin resistance (IR), retinopathy and
      maculopathy in young adults with Type 1 diabetes mellitus. METHODS: A cross
      sectional study at a regional Australian tertiary hospital. Retinal pathology,
      assessed by colour fundus photography, was correlated with two surrogate measures
      of IR: estimated Glucose Disposal Rate (eGDR) and Insulin Sensitivity Score
      (ISS), where lower scores reflect greater IR. RESULTS: 107 patients were
      recruited, with mean age 24.7years, 53% male, and mean duration of disease
      10.8years. Mean eGDR scores (5.6vs 8.0 p<0.001) and ISS (4.7vs 7.9, p<0.001) were
      lower in subjects having at least moderate non-proliferative diabetic retinopathy
      (NPDR; relative to nil/mild-NPDR). Similarly, mean eGDR (4.2vs 6.2, p=0.001) and
      ISS (3.8vs 6.1, p=0.003) were lower in patients with maculopathy. Multivariate
      logistic regression modelling was used to control for confounding. For
      retinopathy severity, a unit increase in eGDR or ISS (representing lower IR) was
      associated with a 50% decrease in odds of moderate-NPDR or worse (eGDR OR 0.5,
      95%CI 0.32-0.77, p=0.002; ISS OR 0.49, 95%CI 0.29-0.84, p=0.01). A unit increase
      in eGDR or ISS was associated with a 46-56% decrease in odds of maculopathy (eGDR
      OR 0.54, 95%CI 0.37-0.81, p=0.003; ISS OR 0.44, 95%CI 0.22-0.88, p=0.02).
      CONCLUSIONS: IR correlates with more severe retinopathy in young adults with Type
      1DM. This is the first description of a correlation between IR and maculopathy in
      Type 1DM, warranting further evaluation. Prospective studies examining whether
      reducing IR can improve microvascular complications are required.

PMID- 28750219
TI  - Continuous glucose monitoring detected hypoglycaemia in the Treating to Target in
      Type 2 Diabetes Trial (4-T).
AB  - AIMS: Hypoglycaemia is a significant risk in insulin treated type 2 diabetes and
      has been associated with future risk of cardiovascular events. We compared the
      frequency of low-glucose events using continuous glucose monitoring (CGM) with
      that of self-reported hypoglycemic events at the end of the first and third years
      of the Treating to Target in Type 2 Diabetes Trial (4-T), which compared
      biphasic, prandial and basal insulin regimens added to sulfonylurea and
      metformin. METHODS: CGM using a Medtronic Gold system was performed in a subgroup
      of 4-T participants. CGM detected low-glucose events were defined at thresholds
      of <=3.0 (CGM3.0) and <=2.2 (CGM2.2) mmol/l. RESULTS: Of the 110 participants,
      106 and 70 had CGM analysable data at the end of years 1 and 3 respectively. In
      both years, the frequency of CGM detected low glucose events was several fold
      higher than that of self-reported hypoglycaemia (symptoms with blood glucose less
      than 3.1mmol/l [<56mg/dl]). At the end of the first year, CGM3.0 and CGM2.2 mean
      (95%CI) event frequencies, expressed at events per participant per year, were 120
      (85, 155) and 41 (21, 61) compared with 17 (8, 29) self-reported events during
      CGM, each p=0.001. The disparity at the end of the third year was similar.
      CONCLUSIONS: These data demonstrate the likely under-reporting of hypoglycaemia
      and of potential hypoglycaemia unawareness in clinical trials. The clinical
      implications of these findings need to be explored further (ISRCTN No
      ISRCTN51125379).

PMID- 28750220
TI  - Effects of medicinal food plants on impaired glucose tolerance: A systematic
      review of randomized controlled trials.
AB  - BACKGROUND: The objective of this systematic review was to assess available
      scientific data on the efficacy and safety of medicinal food plants for the
      treatment of impaired glucose tolerance. METHODS: We included randomized
      controlled trials (RCTs) with a minimum follow-up period of 6weeks. The diagnosis
      was determined by fasting plasma glucose values after two-hour oral glucose
      tolerance testing (OGTT). Two authors independently extracted data and evaluated
      bias. The Cochrane tool of risk of Bias Tool was used. RESULTS: This review
      included ten trials. Most studies were highly biased as data were incomplete or
      reporting was selective. The two-hour fasting plasma glucose after the curcumin
      extract intervention showed statistical significance after 3, 6 and 9months:
      p<0.01. Also, glycosylated haemoglobin levels A1c (HbA1c) values after curcumin
      extract intervention showed statistical significance after 3, 6 and 9months:
      p<0.01. Insulin resistance (HOMA-IR) after curcumin extract intervention showed
      statistical significance after 6months and after 9months: p<0.05 and p<0.01.
      CONCLUSIONS: Curcumin has shown the confident results to be effective for the
      treatment of impaired glucose tolerance. Fenugreek and flaxseed may also be
      effective, but due to low quality of these studies the results must be
      interpreted with caution.

PMID- 28750221
TI  - Cell damage and apoptosis in the hepatopancreas of Eriocheir sinensis induced by
      cadmium.
AB  - Cadmium (Cd) is one of the most common pollutants in the environment and it is
      known to cause a range of tissue damages and apoptosis in invertebrates. In this
      study, we investigated the effect of Cd on the hepatopancreas of the crab
      Eriocheir sinensis, a commercially and ecologically important species of
      crustacean. The crabs were first exposed to water containing different
      concentrations of Cd2+ (0, 0.63, 1.26, 2.52, 5.04 and 10.07mg/L) for 6days.
      Typical morphological characteristics and physiological changes of apoptosis were
      then observed using various methods, including AO/EB double fluorescence
      staining, transmission electron microscopy and DNA fragmentation analysis. The
      results showed that Cd2+ induced cell damage and apoptosis in a concentration
      dependent manner. Transmission electron microscopy revealed the presence of
      cellular swelling and necrosis with reduced number of microvilli on the cell
      surface and damages to individual organelles. The mitochondria became swollen and
      vacuolated. The rough endoplasmic reticulum (Rer) was expanded, with membrane
      rupture and many different sizes of vesicles, suggesting the destruction of
      protein-synthesizing structures in the hepatopancreatic cells. The activities of
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidases (GPx)
      initially increased and subsequently decreased with increasing Cd2+
      concentrations. This was accompanied by increases in malondialdehyde (MDA) and
      H2O2 contents, which led to membrane lipid peroxidation. Crabs exposed to Cd2+
      also displayed significant increases in caspase-3, -8, and -9 activities compared
      to control crabs. Cadmium induced the production and accumulation of ROS in the
      hepatopancreas, which resulted in oxidative damage and abnormal metabolism. Taken
      together, the results indicated that Cd2+ could induce oxidative damage as well
      caspase-dependent apoptosis in E. sinensis hepatopancreas.

PMID- 28750222
TI  - Assessing the relevance of a multiplexed methodology for proteomic biomarker
      measurement in the invertebrate species Gammarus fossarum: A physiological and
      ecotoxicological study.
AB  - Recently, a protein sequence database was built specifically for the sentinel non
      model species Gammarus fossarum using a proteogenomics approach. A quantitative
      multiplexed targeted proteomics assay (using Selected Reaction Monitoring mass
      spectrometry) was then developed for a fast and simultaneous quantification of
      dozens of biomarker peptides specific of this freshwater sentinel crustacean
      species. In order to assess the relevance of this breakthrough methodology in
      ecotoxicology, the response patterns of a panel of 26 peptides reporting for 20
      proteins from the Gammarus fossarum proteome with putative key functional roles
      (homeostasis, osmoregulation, nutrition, reproduction, molting,...) were recorded
      through male and female reproductive cycles and after exposure to environmental
      concentrations of cadmium and lead in laboratory-controlled conditions. Based on
      these results, we validated the implication of annotated vtg-like peptides in the
      oogenesis process, and the implication of Na+/K+ ATPase proteins in the molt
      cycle of organisms. Upon metal (cadmium and lead) contamination, peptides
      belonging to proteins annotated as involved in antioxidant and detoxification
      functions, immunity and molting were significantly down-regulated. Overall, this
      multiplex assay allowed gaining relevant insights upon disruption of different
      main functions in the sentinel species Gammarus fossarum. This breakthrough
      methodology in ecotoxicology offers a valid and high throughput alternative to
      currently used protocols, paving the way for future practical applications of
      proteogenomics-derived protein biomarkers in chemical risk assessment and
      environmental monitoring.

PMID- 28750223
TI  - Associations between flame retardant applications in furniture foam, house dust
      levels, and residents' serum levels.
AB  - Polyurethane foam (PUF) in upholstered furniture frequently is treated with flame
      retardant chemicals (FRs) to reduce its flammability and adhere to rigorous
      flammability standards. For decades, a commercial mixture of polybrominated
      diphenyl ethers (PBDEs) called PentaBDE was commonly applied to foam to fulfill
      these regulations; however, concerns over toxicity, bioaccumulation, and
      persistence led to a global phase-out in the mid-2000s. Although PentaBDE is
      still detected in older furniture, other FR compounds such as tris(1,3
      dichloroisopropyl) phosphate (TDCIPP) and Firemaster(r) 550 (FM550) have been
      increasingly used as replacements. While biomonitoring studies suggest exposure
      is widespread, the primary sources of exposure are not clearly known. Here, we
      investigated the relationships between specific FR applications in furniture foam
      and human exposure. Paired samples of furniture foam, house dust and serum
      samples were collected from a cohort in North Carolina, USA and analyzed for FRs
      typically used in PUF. In general, the presence of a specific FR in the sofa of a
      home was associated with an increase in the concentration of that FR in house
      dust. For example, the presence of PentaBDE in sofas was associated with
      significantly higher levels of BDE-47, a major component of PentaBDE, in house
      dust (10beta=6.4, p<0.001). A similar association was observed with a component
      of FM550, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), with levels that were
      approximately 3 times higher in house dust when FM550 was identified in the sofa
      foam (p<0.01). These relationships were modified by dust loading rates in the
      living room and the ratio of sofa size to room size. Interestingly, levels of
      TDCIPP and tris(1-chloro-2-isopropyl) phosphate (TCIPP) were also higher in dust
      with detections in sofa foam; however, these associations were not statistically
      significant and may suggest there are other prominent sources of these compounds
      in the home. In addition, the presence of PentaBDE in sofa foam was associated
      with significantly higher levels of BDE-47 in serum (p<0.01). These results
      suggest that FR applications in sofas are likely major sources of exposure to
      these compounds in the home.

PMID- 28750224
TI  - Second-hand smoke generated by combustion and electronic smoking devices used in
      real scenarios: Ultrafine particle pollution and age-related dose assessment.
AB  - Aerosol measurements were carried out in a model room where both combustion
      (conventional and hand-rolled cigarettes, a cigar and tobacco pipe) and non
      combustion (e-cigarette and IQOS(r)) devices were smoked. The data were used to
      estimate the dose of particles deposited in the respiratory systems of
      individuals from 3months to 21years of age using the multiple-path particle
      dosimetry (MPPD) model. Regardless of the smoking device, the highest doses were
      received by infants, which reached 9.88*108particles/kg bw during a cigar smoking
      session. Moreover, 60% to 80% of the particles deposited in the head region of a
      3-month-old infant were smaller than 100nm and could be translocated to the brain
      via the olfactory bulb. The doses due to second-hand smoke from electronic
      devices were significantly lower, below 1.60*108particles/kg bw, than those due
      to combustion devices. Dosimetry estimates were 50% to 110% higher for IQOS(r)
      than for e-cigarettes.

PMID- 28750225
TI  - Projected temperature-related deaths in ten large U.S. metropolitan areas under
      different climate change scenarios.
AB  - BACKGROUND: There is an established U-shaped association between daily
      temperature and mortality. Temperature changes projected through the end of
      century are expected to lead to higher rates of heat-related mortality but also
      lower rates of cold-related mortality, such that the net change in temperature
      related mortality will depend on location. OBJECTIVES: We quantified the change
      in heat-, cold-, and temperature-related mortality rates through the end of the
      century across 10 large US metropolitan areas. METHODS: We applied location
      specific projections of future temperature from over 40 downscaled climate models
      to exposure-response functions relating daily temperature and mortality in 10 US
      metropolitan areas to estimate the change in temperature-related mortality rates
      in 2045-2055 and 2085-2095 compared to 1992-2002, under two greenhouse gas
      emissions scenarios (RCP 4.5 and 8.5). We further calculated the total number of
      deaths attributable to temperature in 1997, 2050, and 2090 in each metropolitan
      area, either assuming constant population or accounting for projected population
      growth. RESULTS: In each of the 10 metropolitan areas, projected future
      temperatures were associated with lower rates of cold-related deaths and higher
      rates of heat-related deaths. Under the higher-emission RCP 8.5 scenario, 8 of
      the 10 metropolitan areas are projected to experience a net increase in annual
      temperature-related deaths per million people by 2086-2095, ranging from a net
      increase of 627 (95% empirical confidence interval [eCI]: 239, 1018) deaths per
      million in Los Angeles to a net decrease of 59 (95% eCI: -485, 314) deaths per
      million in Boston. Applying these projected temperature-related mortality rates
      to projected population size underscores the large public health burden of
      temperature. CONCLUSIONS: Increases in the heat-related death rate are projected
      to outweigh decreases in the cold-related death rate in 8 out of 10 cities
      studied under a high emissions scenario. Adhering to a lower greenhouse gas
      emissions scenario has the potential to substantially reduce future temperature
      related mortality.

PMID- 28750226
TI  - Preface to the special issue of the 4th Forum Carpaticum conference "Future of
      the Carpathians: Smart, Sustainable, Inclusive".

PMID- 28750227
TI  - Seasonal distribution of herbicide and insecticide residues in the water
      resources of the vineyard region of La Rioja (Spain).
AB  - Pesticides are needed to maintain high production in the vineyard area of La
      Rioja (Spain), and monitoring their spatial distribution is a priority for
      preserving the quality of natural resources. Accordingly, the purpose of this
      work was to conduct a study to evaluate the presence and seasonal distribution of
      herbicide and insecticide residues in ground and surface waters in this region.
      The monitoring network comprised 12 surface waters and 78 groundwaters, covering
      the three subareas (63,593ha) into which the vineyard region is divided. The
      quality of natural waters was examined through the analysis of twenty-two
      herbicides, eight of their main degradation products, and eight insecticides.
      Pesticides were extracted by solid-phase extraction, and analysed by gas
      chromatography-mass spectrometry or by liquid-chromatography-mass spectrometry.
      The results reveal the presence of most of the herbicides and insecticides
      included in the study in one or more of the samples collected during the four
      campaigns. The herbicide terbuthylazine and its metabolite desethylterbuthylazine
      were the compounds more frequently detected (present in >65% of the samples
      across all the campaigns). Other compounds detected in >50% of the samples in one
      sampling campaign were the herbicides fluometuron, metolachlor, alachlor and
      ethofumesate. Insecticides were present in a small number of samples, with only
      pirimicarb being detected in >25% of the samples in March and June campaigns. The
      results reveal that the sum of compounds detected (mainly herbicides) was higher
      than 0.5MUgL-1 in >50% of the samples, especially in the campaigns with the
      highest application of these compounds. A possible recovery of the quality of the
      waters was detected outside the periods of crop cultivation, although more
      monitoring programmes are needed to confirm this trend with a view to preventing
      and/or maintaining the sustainability of natural resources.

PMID- 28750228
TI  - Radionuclides and soil properties as indicators of glacier retreat in a recently
      deglaciated permafrost environment of the Maritime Antarctica.
AB  - Many ice-free environments in Maritime Antarctica are undergoing rapid and
      substantial environmental changes in response to recent climate trends. This is
      the case of Elephant Point (Livingston Island, South Shetland Islands, SSI),
      where the glacier retreat recorded during the last six decades exposed 17% of
      this small peninsula, namely a moraine extending from the western to the eastern
      coastlines and a relatively flat proglacial surface. In the southern margin of
      the peninsula, a sequence of Holocene raised beaches and several bedrock plateaus
      are also distributed. A main issue in this environment is the role of glacier
      retreat and permafrost controlling the recently formed soils. To this purpose, a
      total of 10 sites were sampled along a transect crossing raised beaches and
      moraine materials following the direction of glacier retreat. At the selected
      sites surface samples were collected until 12cm depth and sectioned at 3cm depth
      intervals to analyse main properties, grain size, pH, electrical conductivity and
      carbonates. Besides, elemental composition and fallout (FRNs) and environmental
      radionuclides (ERNs) were analysed. To assess if profile characteristics within
      the active layer are affected by glacier retreat variations of organic carbon and
      carbon fractions and 137Cs contents were examined. The presence of organic carbon
      (range: 0.13-3.19%), and 137Cs (range: bdl-10.1Bqkg-1) was only found at the
      raised beaches. The surface samples had abundant coarse fractions in rich sandy
      matrix with increasing acidic pH towards the coast. Significant differences were
      found in the elemental composition and the radionuclides between the moraine and
      raised beaches. Soil forming processes are related to the time of exposure of the
      landforms after glacier retreat. The results obtained confirm the potential for
      using geomorphological, edaphic and geochemical data to assess the influence of
      different stages of glacier retreat in recent soils and sediments.

PMID- 28750229
TI  - Improving assessment accuracy for lake biological condition by classifying lakes
      with diatom typology, varying metrics and modeling multimetric indices.
AB  - Site grouping by regions or typologies, site-specific modeling and varying
      metrics among site groups are four approaches that account for natural variation,
      which can be a major source of error in ecological assessments. Using a data set
      from the 2007 National Lakes Assessment project of the USEPA, we compared
      performances of multimetric indices (MMI) of biological condition that were
      developed: (1) with different lake grouping methods, ecoregions or diatom
      typologies; (2) by varying or not varying metrics among site groups; and (3) with
      different statistical techniques for modeling diatom metric values expected for
      minimally disturbed condition for each lake. Hierarchical modeling of MMIs, i.e.
      grouping sites by ecoregions or typologies and then modeling natural variability
      in metrics among lakes within groups, substantially improved MMI performance
      compared to using either ecoregions or site-specific modeling alone. Compared
      with MMIs based on ecoregion site groups, MMI precision and sensitivity to human
      disturbance were better when sites were grouped by diatom typologies and
      assessing performance nationwide. However, when MMI performance was evaluated at
      site group levels, as some government agencies often do, there was little
      difference in MMI performance between the two site grouping methods. Low numbers
      of reference and highly impacted sites in some typology groups likely limited MMI
      performance at the group level of analysis. Varying metrics among site groups did
      not improve MMI performance. Random forest models for site-specific expected
      metric values performed better than classification and regression tree and
      multiple linear regression, except when numbers of reference sites were small in
      site groups. Then classification and regression tree models were most precise.
      Based on our results, we recommend hierarchical modeling in future large scale
      lake assessments where lakes are grouped by ecoregions or diatom typologies and
      site-specific metric models are used to establish expected metric values.

PMID- 28750230
TI  - Spatiotemporal analysis of human exposure to halogenated flame retardant
      chemicals.
AB  - Human exposure to flame retardants occurs in microenvironments due to their
      ubiquitous presence in consumer products and building materials. Recent research
      suggests higher levels of exposure through elevated surface dust (ESD) compared
      to floor dust (FD). However, it is unclear whether this pattern is consistent in
      different microenvironments beyond the home. We hypothesized that time spent in
      various microenvironments will significantly modify the pattern of human exposure
      to flame retardant chemicals in ESD and FD. We tested this hypothesis by
      collecting time activity diaries from 43 participants; and by estimating human
      exposure to 10 polybrominated diphenyl ether and 8 non-polybrominated diphenyl
      ether flame retardant chemicals, based on chemical concentrations measured in
      different microenvironments visited by the participants. The results of paired t
      tests show that, with some notable exceptions, estimates of human exposure to
      most chemicals through ESD are statistically significantly higher for ?PBDE
      (p=0.00) and ?non-PBDEs (p=0.00) than through FD. This study reinforces the need
      to integrate temporal, locational, and elevation dimensions in assessing human
      exposure to potentially toxic flame retardant chemicals.

PMID- 28750231
TI  - Settlement patterns of the coral Acropora millepora on sediment-laden surfaces.
AB  - Successful recruitment in corals is important for the sustenance of coral reefs,
      and is considered a demographic bottleneck in the recovery of reef populations
      following disturbance events. Yet several factors influence larval settlement
      behaviour, and here we quantified thresholds associated with light attenuation
      and accumulated sediments on settlement substrates. Sediments deposited on
      calcareous red algae (CRA) directly and indirectly impacted coral settlement
      patterns. Although not avoiding direct contact, Acropora millepora larvae were
      very reluctant to settle on surfaces layered with sediments, progressively
      shifting their settlement preference from upward to downward facing (sediment
      free) surfaces under increasing levels of deposited sediment. When only upward
      facing surfaces were presented, 10% of settlement was inhibited at thresholds
      from 0.9 to 16mgcm-2 (EC10), regardless of sediment type (carbonate and
      siliciclastic) or particle size (fine and coarse silt). These levels equate to a
      very thin (<150MUm) veneer of sediment that occurs within background levels on
      reefs. Grooves within settlement surfaces slightly improved options for
      settlement on sediment-coated surfaces (EC10: 29mgcm-2), but were quickly
      infilled at higher deposited sediment levels. CRA that was temporarily smothered
      by sediment for 6d became bleached (53% surface area), and inhibited settlement
      at ~7mgcm-2 (EC10). A minor decrease in settlement was observed at high and very
      low light intensities when using suboptimal concentrations of a settlement
      inducer (CRA extract); however, no inhibition was observed when natural CRA
      surfaces along with more realistic diel-light patterns were applied. The low
      deposited sediment thresholds indicate that even a thin veneer of sediment can
      have consequences for larval settlement due to a reduction of optimal substrate.
      And while grooves and overhangs provide more settlement options in high
      deposition areas, recruits settling at these locations may be subject to ongoing
      stress from shading, competition, and sediment infilling.

PMID- 28750232
TI  - Effects of chair yoga therapy on physical fitness in patients with psychiatric
      disorders: A 12-week single-blind randomized controlled trial.
AB  - INTRODUCTION: Since falls may lead to fractures and have serious, potentially
      fatal outcomes, prevention of falls is an urgent public health issue. We examined
      the effects of chair yoga therapy on physical fitness among psychiatric patients
      in order to reduce the risk of falls, which has not been previously reported in
      the literature. METHODS: In this 12-week single-blind randomized controlled trial
      with a 6-week follow-up, inpatients with mixed psychiatric diagnoses were
      randomly assigned to either chair yoga therapy in addition to ongoing treatment,
      or treatment-as-usual. Chair yoga therapy was conducted as twice-weekly 20-min
      sessions over 12 weeks. Assessments included anteflexion in sitting, degree of
      muscle strength, and Modified Falls Efficacy Scale (MFES) as well as QOL,
      psychopathology and functioning. RESULTS: Fifty-six inpatients participated in
      this study (36 men; mean +/- SD age, 55.3 +/- 13.7 years; schizophrenia 87.5%).
      In the chair yoga group, significant improvements were observed in flexibility,
      hand-grip, lower limb muscle endurance, and MFES at week 12 (mean +/- SD: 55.1 +/
      16.6 to 67.2 +/- 14.0 cm, 23.6 +/- 10.6 to 26.8 +/- 9.7 kg, 4.9 +/- 4.0 to 7.0
      +/- 3.9 kg, and 114.9 +/- 29.2 to 134.1 +/- 11.6, respectively). Additionally,
      these improvements were observable six weeks after the intervention was over. The
      QOL-VAS improved in the intervention group while no differences were noted in
      psychopathology and functioning between the groups. The intervention appeared to
      be highly tolerable without any notable adverse effects. CONCLUSIONS: The results
      indicated sustainable effects of 20-min, 12-week, 24-session chair yoga therapy
      on physical fitness. Chair yoga therapy may contribute to reduce the risk of
      falls and their unwanted consequences in psychiatric patients.

PMID- 28750233
TI  - A simple and sensitive UHPLC-Q-TOF-MS/MS method for sophoricoside metabolism
      study in vitro and in vivo.
AB  - Sophoricoside (SOPH) is an isoflavone glycoside isolated from Fructus Sophorae,
      and it has the effects on reproductive system. Currently, a strategy was firstly
      developed to identify the metabolites of SOPH in vitro and in vivo using ultra
      high performance liquid chromatography coupled with hybrid triple quadrupole time
      of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Based on the proposed method, 60
      metabolites were structurally characterized in vivo including 22 phase I and 38
      phase II metabolites, and 4 metabolites in vitro were detected containing 2 phase
      I and 2 phase II metabolites. The results indicated that the metabolic pathways
      mainly included oxidation, reduction, hydrolysis, methylation, sulfate,
      glucuronide, glutamine and glycine conjugation. These results will provide basic
      data for future pharmacological and toxicology studies of SOPH and other
      isoflavone glycoside.

PMID- 28750234
TI  - Identification of a novel component leading to anti-tumor activity besides the
      major ingredient cordycepin in Cordyceps militaris extract.
AB  - In accordance with our previous study that was carried out to identify novel anti
      tumor ingredients, chromatographic separation in combination with an anti-tumor
      activity assay was used for analysis of Cordyceps militaris extract in this
      study. Various modes of chromatography including reversed-phase, cation-exchange
      and anion-exchange were used to separate components of Cordyceps militaris, which
      showed various chemical properties. Anti-tumor activity of each fraction was
      assessed by a Hoechst staining-based apoptosis assay using malignant melanoma
      MeWo cells. By these repeated approaches through chromatographic segregation and
      cell biological assay, we finally succeeded in identifying the target substance
      from a certain fraction that included neutral hydrophilic components using a pre
      column and post-column chlorine adduct ionization LC-APCI-MS method. The target
      substance was a mono-carbohydrate, xylitol, that induced apoptotic cell death in
      MeWo cells but not in normal human OUMS-24 fibroblasts. This is the first study
      showing that Cordyceps militaris extract contains a large amount of xylitol.
      Thus, our results will contribute greatly to uncovering the mysterious
      multifunctional herbal drug Cordyceps militaris as an anti-tumor agent.

PMID- 28750235
TI  - Investigation of the effect of plasma albumin levels on regorafenib-induced
      hepatotoxicity using a validated liquid chromatography-tandem mass spectrometry
      method.
AB  - Regorafenib is an oral multikinase inhibitor indicated for metastatic colorectal
      cancer and gastrointestinal stromal tumour. Due to its extensive plasma protein
      binding and low calculated hepatic extraction ratio, the hepatotoxicity observed
      with usage of the drug may be related to its plasma exposure. To investigate the
      highly dynamic free:bound drug concentration for regorafenib in the plasma, a
      bioanalytical liquid chromatography-tandem mass spectrometric assay was developed
      and validated in human plasma. The concentration range of the assay was 2
      1000ng/mL. Sample preparation was via protein precipitation using acetonitrile
      with sorafenib as the internal standard. The supernatant was injected into an
      ultra-performance liquid chromatographic system coupled to a triple quadrupole
      mass spectrometer. The analytes were separated on an AQUITY UPLC BEH C18 column
      (120A, 1.7MUm, 2.1mm*50mm) and eluted with a gradient elution system. The ions
      were detected in multiple reaction monitoring mode. The linearity, lower limit of
      quantification, intra-day and inter-day precision and accuracy conformed to FDA
      guidelines. The validated method was successfully applied to determine the effect
      of albumin levels in plasma on the extent of protein binding of regorafenib. The
      results indicated that physiologically-relevant levels of albumin were found to
      have no significant effect on the extent of protein binding of regorafenib, hence
      imposing minimal effect on drug disposition.

PMID- 28750236
TI  - Development, validation and application of a GC-MS method for the simultaneous
      detection and quantification of neutral lipid species in Trypanosoma cruzi.
AB  - The development and validation of an analytical method for the simultaneous
      analysis of five neutral lipids in Trypanosoma cruzi epimastigotes by GC-MS is
      presented in this study. The validated method meets all validation parameters for
      all components and the chromatographic conditions have been optimized during its
      development. This analytical method has demonstrated good selectivity, accuracy,
      within-day precision, recovery and linearity in each of the established ranges.
      In addition, detection and quantification limits for squalene, cholesterol,
      ergosterol and lanosterol have been improved and it is worth highlighting the
      fact that this is the first time that squalene-2,3-epoxide validation data have
      been reported. The new validated method has been applied to epimastigotes treated
      with compounds with in vitro anti-T.cruzi activity. This new methodology is
      straightforward and constitutes a tool for screening possible sterol biosynthesis
      pathway inhibitors in Trypanosoma cruzi, one of the most studied targets in
      Chagas disease treatment. Therefore, it is an interesting and useful contribution
      to medicinal chemistry research.

PMID- 28750237
TI  - Competitive adsorption of Pb(II), Cd(II) and Cu(II) onto chitosan-pyromellitic
      dianhydride modified biochar.
AB  - In this work, a novel engineered biochar prepared through modification with
      chitosan and pyromellitic dianhydride (PMDA) was investigated as an adsorbent for
      the removal of heavy metal ions from single metal and mixed-metal solutions (Cd,
      Cu and Pb). Characterization experiments with FTIR and XPS suggested that the
      novel modified biochar had more surface functional groups compare to the pristine
      biochar. Adsorption experiments indicated that the initial pH of the solution
      influenced the ability of biochars to adsorb heavy metals in single- and multi
      metal systems. Moreover, the chitosan-PMDA modified biochar had strong selective
      adsorption of Cu(II). Mechanism studies showed that chemisorption was the major
      mechanism for heavy metal removal by the chitosan-PMDA modified biochar.
      Furthermore, the types of effective functional group for these heavy metal
      removal were different. The NCO group played a dominant role in the process of
      Pb(II) removal, while several N-containing functional groups and CC groups
      participated in the adsorption of Cd(II). The novel engineered biochar had
      selective adsorption capacity for copper due to the N-containing functional
      groups, meanwhile abundant carbonyl groups also participated in the removal of
      copper, and may reduce Cu(II) to Cu(I).

PMID- 28750238
TI  - Highly reversible lithium storage in cobalt 2,5-dioxido-1,4-benzenedicarboxylate
      metal-organic frameworks boosted by pseudocapacitance.
AB  - Exploiting novel metal-organic frameworks (MOFs) as electrode materials with
      superior rate capabilities and understanding their electrochemical behaviour in
      detail are crucial for boosting the application of MOFs in the field of energy
      storage. Herein, we prepared Co2(DOBDC) (DOBDC=2,5-dioxido-1,4
      benzenedicarboxylate) via a hydrothermal method and explored its electrochemical
      performance as an anode material for lithium-ion batteries. The as-prepared
      Co2(DOBDC) MOF exhibits a reversible capacity of 526.1mAhg-1 after 200
      charge/discharge cycles at a current density of 500mAg-1 and also demonstrates an
      impressive rate capability, with a high capacity of 408.2mAhg-1 at a high current
      density of 2Ag-1. Furthermore, synchrotron-based soft X-ray absorption
      spectroscopy (sXAS) and electron paramagnetic resonance (EPR) spectroscopy have
      been applied to investigate the spin state of cobalt in the electrodes at
      different states of charge. Our results suggest that localized electrons in high
      spin (S=3/2) Co2+ in pristine Co2(DOBDC) are gradually delocalized after
      discharging. It was also found that the high rate capability of Co2(DOBDC) is
      mainly ascribed to an ultrafast ion intercalation pseudocapacitance process,
      which results from its unique microporous architecture and adequate specific
      surface that offers sufficient electrode/electrolyte contact and benefits fast
      Li+ ion diffusion.

PMID- 28750239
TI  - Nitrogen-doped carbon quantum dots as fluorescent probe for "off-on" detection of
      mercury ions, l-cysteine and iodide ions.
AB  - The application of fluorescent nanoparticles to the detection of inorganic ions
      and organic compounds has been attracted wide attention recently. In this paper,
      an "off-on" method for highly sensitive and selective detection of Hg2+ and l
      cysteine (l-Cys) or Hg2+ and I- using home-made nitrogen-doped carbon quantum
      dots (N-CQDs) as fluorescent probe was reported. The N-CQDs with a fluorescence
      quantum yield of 42.2% were prepared using tartaric acid, citric acid and
      ethanediamine as the precursors in the oleic acid media. The fluorescence of the
      obtained N-CQDs could be quenched selectively and sensitively by the addition of
      Hg2+ (turn-off) with a detection limit of 83.5nM. When l-Cys or I- was added into
      the N-CQDs-Hg2+ system, the fluorescence was recovered effectively (turn-on).
      This process could be used to the detection of l-Cys or I- with a detection limit
      of 45.8 and 92.3nM, respectively.

PMID- 28750240
TI  - High performance electrochemical glucose sensor based on three-dimensional
      MoS2/graphene aerogel.
AB  - Two-dimensional (2D) nanosheets have been extensively explored as electrode
      materials for the development of high-performance electrochemical biosensors due
      to their unique structural characteristics. Nevertheless, 2D nanosheets suffer
      from sheet aggregation issues limiting the electrical conductivity of layered
      metal sulfides or hydroxides. Here, we report high-performance glucose biosensors
      based on a three-dimensional (3D) aerogel composed of interconnected 2D MoS2 and
      graphene sheet. 3D MoS2/graphene aerogel (MGA) provides a large surface area for
      the effective immobilization of enzymes, and continuous framework of electrically
      conductive graphene sheets. Flow-injection amperometric evaluation of the glucose
      biosensor using a 3D MGA electrode exhibits a rapid response (~4s), a linear
      detection range from 2 to 20mM, a sensitivity of 3.36MUA/mM, and a low limit of
      detection of 0.29mM. Moreover, the interference response from oxidizable species,
      such as ascorbic acid, uric acid and dopamine is negligible at an operating
      potential of -0.45V.

PMID- 28750241
TI  - A polypeptide-mediated synthesis of green fluorescent gold nanoclusters for Fe3+
      sensing and bioimaging.
AB  - In this paper, growth hormone releasing peptide-6 (GHRP-6) is a bioactive
      polypeptide and acts as the reducing agent and capping ligand for synthesis of
      bright green fluorescent gold nanoclusters (GHRP-6-Au NCs) by a simple and
      environmental-friendly aqueous method, with the assistance of NaBr as the
      fluorescent sensitizer. The obtained GHRP-6-Au NCs had high fluorescent quantum
      yield (10.7%), and the fluorescence was strongly quenched by the existence of
      trace Fe3+. Thus, a new and highly sensitive sensor for the assay of Fe3+ was
      constructed based on the analyte-induced fluorescent quenching mechanism. The
      sensor had a low detection limit of 1.4uM (S/N=3) and a wide linear range of 2
      1000uM. Besides, GHRP-6-Au NCs exhibited low cytotoxicity and high
      biocompatibility for cell imaging.

PMID- 28750242
TI  - Rotational diffusion of magnetic nanoparticles in protein solutions.
AB  - The rotational diffusion of polyethylene glycol coated magnetic nanoparticles in
      serum albumin solutions was investigated in a range spanning 0mgmL-1 to 200mgmL
      1. Rotational diffusivities were determined from dynamic magnetic susceptibility
      measurements, which provide a non-optical means to probe rotation of
      nanoparticles in small volume samples. Experimental rotational diffusivities were
      compared to those estimated using the Stokes-Einstein relation and macroscopic
      measurements of the viscosity of the protein solutions. Excellent agreement was
      found between experimental measurements and theoretical predictions for serum
      albumin solutions buffered at physiological pH and for serum albumin solutions at
      acidic pH prepared using simple acids at physiological ionic strengths. For serum
      albumin solutions prepared using citrate buffer at acidic pH, we observed a
      discrepancy between the experimental rotational diffusivity and that predicted
      from the Stokes-Einstein relation. In contrast, when the pH was adjusted with a
      simple acid and salt at physiological ionic strength we observed agreement
      between the experimental rotational diffusivity and that predicted from the
      Stokes-Einstein relation. Because of the role of citrate ions in causing protein
      aggregation, we believe these observations suggest that dynamic magnetic
      susceptibility measurement of the rotational diffusivity of the nanoparticles is
      sensitive to gelation/crosslinking of proteins.

PMID- 28750243
TI  - Synthesis and characterization of Fe0/TiO2 nano-composites for ultrasound
      assisted enhanced catalytic degradation of reactive black 5 in aqueous solutions.
AB  - In the present study, nanocomposites (NCs) of zero valent iron nanoparticles (Fe0
      NPs) and titanium dioxide nanoparticles (Fe0/TiO2 NCs) were prepared by coating
      Fe0 NPs onto the surface of TiO2 NPs through borohydride reduction of Fe(II) salt
      for the ultrasound assisted removal/ degradation of reactive black 5 (RB5) dye
      from aqueous solutions. Morphological and structural characterizations of the
      Fe0/TiO2 NCs were performed by FE-SEM, HR-TEM, XRD, XPS and Brunauer-Emmett
      Teller (BET) method. The Fe0/TiO2 NCs exhibited highly efficient ultrasonic
      degradation/decolourization of RB5, compared to TiO2 NPs counterpart. In the
      presence of ultrasonic irradiation, 0.25g/L of Fe0/TiO2 NCs showed complete
      removal of 100mg/L RB5 dye within 10min of reaction. An increase in RB5 removal
      efficiency was obtained with decrease in initial concentration and solution pH,
      whereas it was decreased with decrease in the amount of Fe0/TiO2 NCs. The rate of
      RB5 degradation was in good agreement with the pseudo-first-order kinetic model.
      Higher RB5 removal efficiency was observed at a higher ultrasonic power level.
      Coexisting NO3- and SO42- ions had only a minor impact on the removal of RB5,
      whereas, CO32- ions considerably affected the% removal of RB5 using Fe0/TiO2 NCs.
      Regeneration/reusability experiments revealed that Fe0/TiO2 NCs could be reused
      efficiently up to 7th removal cycle without considerable loss of their original
      RB5 removal performance. Liquid chromatography-mass spectrometry (LC-MS) study,
      used for the detection of the RB5 degradation products showed that the
      degradation mechanism proceeds via the reductive cleavage of the azo linkage of
      the dye which produced 1-sulfonic, 2(4-aminobenzenesulfonyl) ethanol as the
      stable end product.

PMID- 28750244
TI  - Transparent, conductive, and superhydrophobic nanocomposite coatings on polymer
      substrate.
AB  - Transparent, conductive, and superhydrophobic nanocomposite coatings were
      fabricated on the polyethylene terephthalate substrate by a spray method.
      Different concentrations of multi-walled carbon nanotubes (MWCNTs) entwined with
      SiO2 nanoparticles, which originated from the hydrolysis and condensation of
      tetraethyl orthosilicate, were sprayed to form MWCNTs/SiO2 nanocomposite
      coatings. The coatings were characterized by scanning electron microscopy,
      contact angle measurements, and other analytical techniques. The surface
      morphology, hydrophobicity, transparency, and conductivity of the nanocomposite
      coating were found to be strongly dependent on the MWCNT concentration. With
      increasing MWCNT concentration, the hydrophobicity increased first and then
      decreased, and the optical transmittance and sheet resistance decreased. The
      enhanced hydrophobicity was associated with the surface microstructure and
      chemical composition of the coating. The decreased hydrophobicity resulted mainly
      from the decrease in the trapped air between the water droplet and the
      nanocomposite coating. Owing to the hierarchically porous 3-dimensional
      microstructure and opportune fluorinated MWCNT content, the nanocomposite coating
      with 0.2wt% MWCNTs exhibited the best hydrophobicity with a contact angle of
      156.7 degrees , good transparency with 95.7% transmittance and relatively high
      conductivity with a sheet resistance of 3.2*104Omegasq-1.

PMID- 28750245
TI  - Antecedents and outcomes of nurses' rest break organization: A scoping review.
AB  - OBJECTIVES: To prevent an accumulation of strain during work and to reduce error
      risk, many countries have made rest breaks mandatory. In the nursing literature,
      insufficient rest break organization is often reported. However, the outcomes of
      nurses' rest break organization and its anteceding factors are less clear. DATA
      SOURCES: We searched for academic literature on nurses' rest break organization
      in electronic databases (PubMed, Medline, PsycArticles, PsycINFO, CINAHL). REVIEW
      METHODS: Our search yielded 93 potentially relevant articles published between
      01/1990 and 04/2016. The final sample in our scoping review consisted of 36
      publications and included data from 35 independent and international study
      samples and two reviews. RESULTS: Several studies reported a high prevalence of
      missed, interrupted, or delayed rest breaks in nursing. Nurses' rest breaks often
      related to better physical and mental well-being but did not affect motivational
      outcomes and performance systematically. Results on the effects of napping breaks
      were inconsistent. Rest break activities and high quality rest break areas are
      further factors that relieve nurses from job demands and can be helpful in coping
      with them. Several study results indicated that temporal and quantitative work
      demands, job resources, and individual characteristics influence rest break
      organization. However, most of these findings stem from studies that do not allow
      causal conclusions to be drawn. CONCLUSIONS: Well-designed rest breaks influence
      nurses' occupational well-being and behavior positively. However, the mechanisms
      and moderating break-, work-, and person-related factors involved in producing
      these effects are not well understood today. Thus, further theory building and
      stronger empirical data are needed.

PMID- 28750246
TI  - Healing and/or breaking? The mental health implications of repeated economic
      insecurity.
AB  - Current literature confirms the negative consequences of contemporaneous economic
      insecurity for mental health, but ignores possible implications of repeated
      insecurity. This paper asks how much a person's history of economic insecurity
      matters for psychological distress by contrasting the implications of two models.
      Consistent with the health capital literature, the Healing model suggests
      psychological distress is a stock variable affected by shocks from life events,
      with past events having less impact than more recent shocks. Alternatively, the
      Breaking Point model considers that high levels of distress represent a distinct
      shift in life state, which occurs if the accumulation of past life stresses
      exceeds some critical value. Using five cycles of Canadian National Population
      Health Survey data (2000-2009), we model the impact of past economic insecurity
      shocks on current psychological distress in a way that can distinguish between
      these hypotheses. In our sample of 1775 males and 1883 females aged 25 to 64, we
      find a robust healing effect for one-time economic insecurity shocks. For males,
      only a recent one-time occurrence of economic insecurity is predictive of higher
      current psychological distress (0.19 standard deviations). Moreover, working age
      adults tend to recover from past accumulated experiences of economic insecurity
      if they were recently economically secure. However, consistent with the Breaking
      Point hypothesis, males experiencing three or four cycles of recent insecurity
      are estimated to have a level of current psychological distress that is 0.26-0.29
      standard deviations higher than those who were employed and job secure throughout
      the same time period. We also find, consistent with other literature, distinct
      gender differences - for working age females, all economic insecurity variables
      are statistically insignificant at conventional levels. Our results suggest that
      although Canadians are resilient to one-time insecurity shocks, males most
      vulnerable to repeated bouts suffer from elevated levels of psychological
      distress.

PMID- 28750248
TI  - How to tame an endogenous retrovirus: HERVH and the evolution of human
      pluripotency.
AB  - HERVH is one of the most successful endogenous retrovirus in the human genome.
      Relative to other endogenous retroviruses, slower degradation of HERVH internal
      sequences indicates their potential relevance for the host. HERVH is
      transcriptionally active during human preimplantation embryogenesis. In this
      review, we focus on the role of HERVH in regulating human pluripotency. The HERVH
      mediated pluripotency network has been evolved recently in primates.
      Nevertheless, it became an essential feature of human pluripotency. We discuss
      how HERVH modulates the human pluripotency network by providing alternative
      transcription factor binding sites, functioning as a long-range enhancer, and as
      being a major source for pluripotency specific long non-coding RNAs and chimeric
      transcripts.

PMID- 28750247
TI  - Macaque monkeys in Zika virus research: 1947-present.
AB  - Zika virus was first isolated in 1947 from an exotic rhesus macaque. Nearly 70
      years later, the emergence of Zika virus in the Americas and its newly described
      association with birth defects has motivated the development of captive macaque
      monkey models of human Zika virus infection. This review describes similarities
      between macaque and human Zika virus pathogenesis and discusses specific
      advantages and disadvantages of using macaques instead of other laboratory animal
      models. In particular, macaques provide an outstanding model for understanding in
      utero Zika virus infections that are essential for evaluating preclinical
      interventions for use in pregnancy.

PMID- 28750249
TI  - Fall risk and function in older women after gynecologic surgery.
AB  - PURPOSE OF STUDY: To examine change in balance-related fall risk and daily
      functional abilities in the first 2 post-operative weeks and up to 6 weeks after
      gynecologic surgery. MATERIALS AND METHODS: Prospective cohort study in
      gynecologic surgery patients age 65 and older. Balance confidence (Activities
      specific Balance Confidence Scale) and functional status (basic and instrumental
      activities of daily living) were recorded pre- and post-operatively daily for 1
      week and twice the second week. Physical performance balance and functional
      mobility were measured pre- and 1 week post-operatively using the Tinetti Fall
      Risk Scale, Timed Up and Go, and 6-Minute Walk test. Measures were repeated 6
      weeks after surgery. Non-parametric tests for paired data were used comparing
      scores baseline to post-operative (POD) 7 and to POD 42. RESULTS: Median age was
      72 years (range 65-88). Fall risk was elevated during the first 2 post-operative
      weeks, greatest on the median discharge day, POD 2 (p<0.01). Balance performance
      and functional mobility at 1 week were significantly lower than baseline
      (p<0.01). Functional abilities declined, including new dependence in medication
      management at home in 22% of these independent and cognitively intact women.
      CONCLUSIONS: After gynecologic surgery, older women's fall risk is highest on POD
      2 and remains elevated from baseline for 2 weeks. Functional limitations in the
      early home recovery period include the anticipated (bathing, cooking, etc.) and
      some unanticipated (medication management) ones. This information may help with
      post-operative discharge planning.

PMID- 28750250
TI  - Philosophical and theoretical content of the nursing discipline in academic
      education: A critical interpretive synthesis.
AB  - BACKGROUND: Nursing as clinical practice, management and research are based on
      nursing philosophy and theory. Thus, the philosophical and theoretical content is
      required to be incorporated in academic education in order to enable nurses'
      skills for reflection, analysis, and thinking about the profession. OBJECTIVE:
      The aim of this review was to describe what is known of the philosophical and
      theoretical content of the nursing discipline within academic education. DESIGN:
      A critical interpretive synthesis (CIS). METHODS: Electronic searches were
      performed across four databases, CINAHL, Scopus, Medline, and Web of Science, for
      papers published in English from 1980 to 2016. The selection of original articles
      was based on stages, and inclusion and exclusion criteria were used. Quality of
      the selected papers were evaluated by method sensitive appraisal criteria. The
      five phases of CIS were used to combine the selected data. RESULTS: The searches
      resulted 9148 titles, whereas 13 were selected. Nurses need philosophical and
      theoretical education in order to be aware of human health and explain the
      complexity of the human experience of illness. The philosophy of science, the
      philosophy of care, and theory development were highlighted as the key contents
      in nursing academic education as these subjects are central to the discipline
      that ensures that nurses acquire advanced skills. A model was developed that
      linked disciplinary issues the progression nursing science through the influence
      of advanced skills. CONCLUSIONS: Based on the findings in this study the
      philosophical and theoretical content of nursing discipline crates a basis for
      the academic education and enables a professional and exclusive vision for
      nurses. It provides an overall understanding of people's lives and support nurses
      to achieve deeper awareness of the meaning of illness and health in a person
      lifespan what is needed on the evidence-based decision making.

PMID- 28750251
TI  - Blood borne virus testing of 2250 patients in an unusual, repeated dental patient
      notification exercise: challenges faced and lessons learnt.
AB  - OBJECTIVES: The objectives of this study were to ascertain the risk created for
      patients of two dental practices where infection control was found to be
      inadequate, and if the risk was deemed to be significant, initiate an
      investigation involving notification and blood borne virus (BBV) testing to
      establish if any patient-to-patient BBV transmissions had occurred as a result of
      these infection control breaches. STUDY DESIGN: A case study. METHODS: A public
      health investigation and patient notification. Investigations involved practice
      inspections, staff interviews and examination of invoices. The practices were not
      fully cooperative during the investigation and provided misleading information
      regarding the allegations. This led to two patient notification exercises, as
      more serious breaches were uncovered following the first notification exercise.
      Risk assessments of BBV transmission likelihood were undertaken and informed the
      nature of the advice given to patients. RESULTS: The health board wrote to 5100
      patients informing them of the situation. BBV testing was offered in the second
      notification exercise and 2250 patients opted to be tested for HIV, hepatitis B
      and hepatitis C. There were no new cases of HIV or hepatitis B but less than five
      patients were found to be positive for hepatitis C. None of these cases were
      proven to have contracted their infection as a result of the dental infection
      control lapses. CONCLUSIONS: This incident was unusual in that the practice was
      found to be repeatedly and knowingly putting patients at risk, and attempts were
      made to cover up breaches during the investigation. In future, health boards
      would benefit from a risk assessment tool to aid decision making regarding
      notification exercises, and whether testing is indicated where risk to patients
      is low. This would help ensure that notification exercises do more good than
      harm.

PMID- 28750252
TI  - Neural correlates of bilingual language control during interlingual homograph
      processing in a logogram writing system.
AB  - Bilingual studies using alphabetic languages have shown parallel activation of
      two languages during word recognition. However, little is known about the brain
      mechanisms of language control during word comprehension with a logogram writing
      system. We manipulated the types of words (interlingual homographs (IH),
      cognates, and language-specific words) and the types of participants (Chinese
      (L1)-Japanese (L2) bilinguals vs. Japanese monolinguals). Greater activation was
      found in the bilateral inferior frontal gyri, supplementary motor area, caudate
      nucleus and left fusiform gyrus, when the bilinguals processed IH, as compared to
      cognates. These areas were also commonly activated when the bilinguals processed
      L2 control words during an L1 lexical decision task. The areas function as the
      task/decision system that plays a role in cognitive control for resolving
      response conflict. Furthermore, the anterior cingulate cortex, left thalamus, and
      left middle temporal gyrus were activated during IH processing, suggesting
      resolution of the semantic conflict at the stimulus level (i.e., one logographic
      word having different meanings in the two languages).

PMID- 28750253
TI  - Associations between butane hash oil use and cannabis-related problems.
AB  - BACKGROUND: High-potency cannabis concentrates are increasingly popular in the
      United States, and there is concern that use of high-potency cannabis might
      increase risk for cannabis-related problems. However, little is known about the
      potential negative consequences of concentrate use. This study reports on
      associations between past-year use of a high-potency cannabis concentrate, known
      as butane hash oil (BHO), and cannabis-related problems. METHODS: A sample of 821
      college students were recruited to complete a survey about their health and
      behavior. Participants who had used cannabis in the past year (33%, n=273)
      completed questions about their cannabis use, including their use of BHO and
      cannabis-related problems in eight domains: physical dependence, impaired
      control, academic-occupational problems, social-interpersonal problems, self-care
      problems, self-perception, risk behavior, and blackouts. RESULTS: Approximately
      44% (n=121) of past-year cannabis users had used BHO in the past year. More
      frequent BHO use was associated with higher levels of physical dependence
      (RR=1.8, p<0.001), impaired control (RR=1.3, p<0.001), cannabis-related
      academic/occupational problems (RR=1.5, p=0.004), poor self-care (RR=1.3,
      p=0.002), and cannabis-related risk behavior (RR=1.2, p=0.001). After accounting
      for sociodemographic factors, age of onset of cannabis use, sensation seeking,
      overall frequency of cannabis use, and frequency of other substance use, BHO use
      was still associated with higher levels of physical dependence (RR=1.2, p=0.014).
      CONCLUSIONS: BHO use is associated with greater physiological dependence on
      cannabis, even after accounting for potential confounders. Longitudinal research
      is needed to determine if cannabis users with higher levels of physiological
      dependence seek out BHO and/or if BHO use increases risk for physiological
      dependence.

PMID- 28750254
TI  - Prediction of incidence and stability of alcohol use disorders by latent
      internalizing psychopathology risk profiles in adolescence and young adulthood.
AB  - BACKGROUND: Comorbid internalizing mental disorders in alcohol use disorders
      (AUD) can be understood as putative independent risk factors for AUD or as
      expressions of underlying shared psychopathology vulnerabilities. However, it
      remains unclear whether: 1) specific latent internalizing psychopathology risk
      profiles predict AUD-incidence and 2) specific latent internalizing comorbidity
      profiles in AUD predict AUD-stability. AIMS: To investigate baseline latent
      internalizing psychopathology risk profiles as predictors of subsequent AUD
      incidence and -stability in adolescents and young adults. METHODS: Data from the
      prospective-longitudinal EDSP study (baseline age 14-24 years) were used. The
      study-design included up to three follow-up assessments in up to ten years. DSM
      IV mental disorders were assessed with the DIA-X/M-CIDI. To investigate risk
      profiles and their associations with AUD-outcomes, latent class analysis with
      auxiliary outcome variables was applied. RESULTS: AUD-incidence: a 4-class model
      (N=1683) was identified (classes: normative-male [45.9%], normative-female
      [44.2%], internalizing [5.3%], nicotine dependence [4.5%]). Compared to the
      normative-female class, all other classes were associated with a higher risk of
      subsequent incident alcohol dependence (p<0.05). AUD-stability: a 3-class model
      (N=1940) was identified with only one class (11.6%) with high probabilities for
      baseline AUD. This class was further characterized by elevated substance use
      disorder (SUD) probabilities and predicted any subsequent AUD (OR 8.5, 95% CI 5.4
      13.3). CONCLUSIONS: An internalizing vulnerability may constitute a pathway to
      AUD incidence in adolescence and young adulthood. In contrast, no indication for
      a role of internalizing comorbidity profiles in AUD-stability was found, which
      may indicate a limited importance of such profiles - in contrast to SUD-related
      profiles - in AUD stability.

PMID- 28750255
TI  - Effect of anti-muscarinic autoantibodies on leukocyte function in Sjogren's
      syndrome.
AB  - Patients with primary Sjogren's syndrome, a systemic autoimmune disease, have
      been shown to have serum autoantibodies that react with the muscarinic
      acetylcholine type 3 receptor (M3R).Primary Sjogren's syndrome is a systemic
      autoimmune disease. Patients with primary Sjogren's syndrome have been shown to
      have serum autoantibodies that react with the muscarinic acetylcholine type 3
      receptor (M3R). Leukopenia has been reported to be significantly more common in
      primary Sjogren's syndrome patients who have anti-M3R-autoantibodies in their
      sera. In this study, we investigated whether these anti-M3R autoantibodies have
      effects on M3R and MHCI expression in Jurkat T cells. Purified IgG antibodies
      were isolated from the serum of healthy individuals and primary Sjogren's
      syndrome patients. Jurkat cell line was used to represent T lymphocytes. In situ
      immunofluorescence confocal microscopy was used to confirm the binding reactivity
      of primary Sjogren's syndrome IgG antibodies to M3R. Co-immunoprecipitation and
      immunofluorescence results suggested a direct interaction between M3R and MHC I.
      Co-internalization of M3R and MHC I was observed when Jurkat cells were exposed
      to the primary Sjogren's syndrome IgG, but this primary Sjogren's syndrome IgG
      induced co-internalization of M3R and MHC I was prevented by the presence of
      exogenous IFN-gamma. Primary Sjogren's syndrome IgG itself did not affect the
      viability of Jurkat cells, but Jurkat cells exposed to primary Sjogren's syndrome
      IgG were observed to undergo significant cell death when co-cultured with primary
      Natural Killer cells. Our results suggest that anti-M3R autoantibodies in primary
      Sjogren's syndrome induce downregulation of plasma membrane-resident M3R and MHC
      class I molecules in leukocytes followed by NK cell-mediated cell death. This
      mechanism may explain the frequency of leukopenia occurrence in patients with
      primary Sjogren's syndrome.

PMID- 28750256
TI  - Genetically encoded sensors for monitoring the transport and concentration of
      nitrogen-containing and phosphorus-containing molecules in plants.
AB  - Nitrogen and phosphorus are macronutrients indispensable for plant growth. The
      acquisition and reallocation of both elements require a multitude of dedicated
      transporters that specifically recognize inorganic and organic forms of nitrogen
      and phosphorous. Although many transporters have been discovered through elegant
      screening processes and sequence homology, many remain uncharacterized for their
      functions in planta. Genetically encoded sensors for nitrogen and phosphorous
      molecules offer a unique opportunity for studying transport mechanisms that were
      previously inaccessible. In the past few years, sensors for some of the key
      nitrogen molecules became available, and many improvements have been made for
      existing sensors for phosphorus molecules. Methodologies for detailed in vivo
      analysis also improved. We summarize the recent improvements in genetically
      encoded sensors for nitrogen and phosphorus molecules, and the discoveries made
      by using such sensors.

PMID- 28750257
TI  - The endodermis, a tightly controlled barrier for nutrients.
AB  - Plant roots acquire nutrients from the soil and transport them upwards to the
      aerial parts. To reach the central vasculature of the root, water and nutrients
      radially cross all external cell layers. The endodermis surrounds the vascular
      tissues and forms diffusion barriers. It thereby compartmentalizes the root and
      allows control of nutrient transport from the soil to the vasculature, as well as
      preventing backflow of nutrients from the stele. To achieve this role, endodermal
      cells undergo two specialized differentiations states consisting of deposition of
      two impermeable polymers in the cell wall: lignin, forming the Casparian strips,
      and suberin lamellae. Recent publications showed that endodermal barrier
      formation is not a hard-wired, irreversible process. Synthesis and degradation of
      suberin lamellae is highly regulated by plant hormones in response to nutrient
      stresses. Moreover, Casparian strip continuity seems to be constantly checked by
      two small peptides produced in the vasculature that diffuse into the apoplastic
      space in order to test endodermal barrier integrity. This review discusses the
      recent understanding of endodermal barrier surveillance and plasticity and its
      role in plant nutrition.

PMID- 28750258
TI  - Myoelectronic signal-based methodology for the analysis of handwritten
      signatures.
AB  - With the overall aim of improving the synthesis of handwritten signatures, we
      have studied how muscle activation depends on handwriting style for both text and
      flourish. Surface electromyographic (EMG) signals from a set of twelve arm and
      trunk muscles were recorded in synchronization with handwriting produced on a
      digital Tablet. Correlations between these EMG signals and handwritten trajectory
      signals were analyzed so as to define the sequence of muscles activated during
      the different parts of the signature. Our results establish a correlation between
      the speed of the movement, stroke size, handwriting style and muscle activation.
      Muscle activity appeared to be clustered as a function of movement speed and
      handwriting style, a finding which may be used for filter design in a signature
      synthesizer.

PMID- 28750259
TI  - Impact of series length on statistical precision and sensitivity of
      autocorrelation assessment in human locomotion.
AB  - Long-range autocorrelations (LRA) are a robust feature of rhythmic movements,
      which may provide important information about neural control and potentially
      constitute a powerful marker of dysfunction. A clear difficulty associated with
      the assessment of LRA is that it requires a large number of cycles to generate
      reliable results. Here we investigate how series length impacts the reliability
      of LRA assessment. A total of 94 time series extracted from walking or cycling
      tasks were re-assessed with series length varying from 64 to 512 data points. LRA
      were assessed using an approach combining the rescaled range analysis or the
      detrended fluctuation analysis (Hurst exponent, H), along with the shape of the
      power spectral density (alpha exponent). The statistical precision was defined as
      the ability to obtain estimates for H and alpha that are consistent with their
      theoretical relationship, irrespective of the series length. The sensitivity
      consisted of testing whether significant differences between experimental
      conditions found in the original studies when considering 512 data points
      persisted with shorter series. We also investigate the use of evenly-spaced
      diffusion plots as a methodological improvement of original version of methods
      for short series. Our results show that the reliable assessment of LRA requires
      512 data points, or no shorter than 256 data points provided that more robust
      methods are considered such as the evenly-spaced algorithms. Such series can be
      reasonably obtained in clinical populations with moderate, or even more severe,
      gait impairments and open the perspective to extend the use of LRA assessment as
      a marker of gait stability applicable to a broad range of locomotor disorders.

PMID- 28750260
TI  - Effects of dual task difficulty in motor and cognitive performance: Differences
      between adults and adolescents.
AB  - In the present study our aim was to compare dual-task performance in thirteen
      adolescents and fifteen young adults while concurrently performing a cognitive
      and a motor task. The postural control variables were obtained under three
      different conditions: i) bipedal stance, ii) tandem stance and iii) unipedal
      stance. The cognitive task consisted of a backward digit span test in which the
      participants were asked to memorize a sequence of numbers and then repeat the
      number in reverse order at three different difficulty levels (i.e. with 3, 4 and
      5 digits). The difficulty of the cognitive task was seen to have different
      effects on adolescents and young adults. Adolescents seem to prioritize postural
      control during high difficulty postural conditions while a cross-domain
      competition model appeared in easy postural conditions.

PMID- 28750261
TI  - MAIT cells in infectious diseases.
AB  - In humans, MAIT cells represent the most abundant T cell subset reacting against
      bacteria. Their frequency in the blood is decreased in a large variety of
      infectious diseases of either bacterial or viral origin. MAIT cells accumulate at
      the site of bacterial infection and are protective in experimental infection
      models. Recent epidemiological evidence supports an implication of MAIT cells in
      protecting against tuberculosis. MAIT cells can be activated either through
      direct recognition of microbial ligands or by inflammatory cytokines such as IL
      12 and IL-18. MAIT cells secrete IFN-gamma, IL-17 and/or other effector molecules
      according to the context of triggering. MAIT cells can kill bacterially infected
      epithelial cells in vitro. Herein, we summarize and discuss the data suggesting a
      role for MAIT cells in infectious diseases.

PMID- 28750262
TI  - Limited diagnostic value of a multiplexed gastrointestinal pathogen panel for the
      detection of adenovirus infection in an oncology patient population.
AB  - BACKGROUND: Diagnosis of Adenovirus infections in transplant patients may be
      accomplished using either plasma or stool samples. IVD-cleared multiplexed
      gastrointestinal (GI) PCR panels offer an option for rapid testing of stool
      samples but most only target Adenovirus (HAdV) types F40/41. OBJECTIVES: Given
      the potential significance of a positive adenovirus test in an immunocompromised
      patient, we sought to determine the frequency of type 40/41 in our patient
      population and the utility of a readily available multiplexed, FDA-cleared GI
      Panel for the detection of adenovirus infections. STUDY DESIGN: A total of 215
      specimens from immunocompromised patients mostly with hematologic malignancy or
      transplant recipients were evaluated including 107 plasma samples, 85 stool
      samples and 23 respiratory samples. Genotyping was performed successfully on 122
      specimens. RESULTS: The most common type detected in all samples including stools
      was Adenovirus C/2. In a subset of patients with multiple specimen types tested,
      similar types were detected in all samples. CONCLUSIONS: Although Adenovirus
      F40/41 is the most common enteric type, Adenovirus C/2 was the most common type
      identified in stools and subsequently plasma samples of our patient population.
      Implementation of assays that have wide reactivity for most adenovirus types is
      essential for optimal diagnostic yield.

PMID- 28750263
TI  - Biomechanical differences between cases with chronic exertional compartment
      syndrome and asymptomatic controls during walking and marching gait.
AB  - Chronic exertional compartment syndrome is a significant problem in military
      populations that may be caused by specific military activities. This study aimed
      to investigate the kinematic and kinetic differences in military cases with
      chronic exertional compartment syndrome and asymptomatic controls. 20 males with
      symptoms of chronic exertional compartment syndrome of the anterior compartment
      and 20 asymptomatic controls were studied. Three-dimensional lower limb
      kinematics and kinetics were compared during walking and marching. Cases were
      significantly shorter in stature and took a relatively longer stride in relation
      to leg length than controls. All kinematic differences identified were at the
      ankle. Cases demonstrated increased ankle plantarflexion from mid-stance to toe
      off. Cases also demonstrated less ankle inversion at the end of stance and early
      swing phases. Lower ankle inversion moments were observed during mid-stance. The
      anthropometric and biomechanical differences demonstrated provide a plausible
      mechanism for the development of chronic exertional compartment syndrome in this
      population. The shorter stature in combination with the relatively longer stride
      length observed in cases may result in an increased demand on the anterior
      compartment musculature during ambulation. The results of this study, together
      with clinical insights and the literature suggest that the suppression of the
      walk-to-run stimulus during group marches may play a significant role in the
      development of chronic exertional compartment syndrome within a military
      population. The differences in joint angles and moments also suggest an
      impairment of the muscular control of ankle joint function, such as a reduced
      effectiveness of tibialis anterior. It is unclear whether this is a cause or
      consequence of chronic exertional compartment syndrome.

PMID- 28750264
TI  - The perpetrators of medical child abuse (Munchausen Syndrome by Proxy) - A
      systematic review of 796 cases.
AB  - INTRODUCTION: Little is known about the perpetrators of medical child abuse (MCA)
      which is often described as "Munchausen's syndrome by proxy" or "factitious
      disorder imposed on another". The demographic and clinical characteristics of
      these abusers have yet to be described in a sufficiently large sample. We aimed
      to address this issue through a systematic review of case reports and series in
      the professional literature. METHOD: A systematic search for case reports and
      series published since 1965 was undertaken using MEDLINE, Web of Science and
      EMBASE. 4100 database records were screened. A supplementary search was then
      conducted using GoogleScholar and reference lists of eligible studies. Our search
      yielded a total sample of 796 perpetrators: 309 from case reports and 487 from
      case series. Information extracted included demographic and clinical
      characteristics, in addition to methods of abuse and case outcomes. RESULTS:
      Nearly all abusers were female (97.6%) and the victim's mother (95.6%). Most were
      married (75.8%). Mean caretaker age at the child's presentation was 27.6 years.
      Perpetrators were frequently reported to be in healthcare-related professions
      (45.6%), to have had obstetric complications (23.5%), or to have histories of
      childhood maltreatment (30%). The most common psychiatric diagnoses recorded were
      factitious disorder imposed on self (30.9%), personality disorder (18.6%), and
      depression (14.2%). CONCLUSIONS: From the largest analysis of MCA perpetrators to
      date, we provide several clinical recommendations. In particular, we urge
      clinicians to consider mothers with a personal history of childhood maltreatment,
      obstetric complications, and/or factitious disorder at heightened risk for MCA.
      Longitudinal studies are required to establish the true prognostic value of these
      factors as our method may have been vulnerable to publication bias.

PMID- 28750265
TI  - Childhood cumulative contextual risk and depression diagnosis among young adults:
      The mediating roles of adolescent alcohol use and perceived social support.
AB  - This study examined associations between cumulative contextual risk in childhood
      and depression diagnosis in early adulthood, testing two adolescent mediating
      mechanisms, alcohol use and perceived social support from family and friends,
      while accounting for the stability of internalizing problems over time and
      examining possible gender moderation. Multiple group mediation analyses were
      conducted using parent- and adolescent-report as well as hospital records data
      from the Northern Finland Birth Cohort 1986 (N = 6963). Our analyses demonstrated
      that the association between cumulative contextual risk in childhood and
      depression diagnosis in adulthood is mediated by adolescent alcohol use and
      perceived social support both for boys and girls. The findings highlight
      potentially malleable mediating mechanisms associated with depression in
      vulnerable youth that could be targets in selective depression preventive
      interventions.

PMID- 28750266
TI  - The role of appearance schematicity in the internalization of media appearance
      ideals: A panel study of preadolescents.
AB  - Individuals who are more strongly invested in their appearance, appearance
      schematics, have a tendency to engage in appearance-related comparison.
      Appearance schematicity consists of two components. The self-evaluative component
      concerns the degree to which appearance is central to self-worth, referred to as
      dysfunctional appearance beliefs. Motivational salience refers to the engagement
      in behaviors designed to enhance appearance, such as body surveillance. Based on
      a three-wave panel survey of 973 Flemish preadolescents (Mage = 11.15, SD = 1.13)
      we found that the motivational and self-evaluative components had a different
      impact on media internalization. For preadolescents who engaged in more body
      surveillance, watching television resulted in more media internalization. For
      preadolescents who had fewer dysfunctional appearance beliefs, watching
      television resulted in more media internalization. These findings suggest that
      appearance schematicity is an important susceptibility variable in the
      relationship between TV-exposure and media internalization, and emphasize the
      importance of investigating individual dispositions beyond gender differences.

PMID- 28750267
TI  - Emotional intelligence and social skills on self-efficacy in Secondary Education
      students. Are there gender differences?
AB  - Self-efficacy affects our students' academic results, which may be related to
      people's social skills and emotional intelligence. This study included 1402
      (50.71% males) Secondary Education Spanish students (12-17 years), and analysed
      the relation of self-efficacy with emotional intelligence and social skills. It
      showed how these constructs were related, and how the self-efficacy perceived by
      students varied according to their social skills and emotional intelligence.
      Gender did not influence self-efficacy, social skills and emotional intelligence.
      These variables showed similar correlation indices in females and males. Self
      efficacy was related with social skills and emotional intelligence in Secondary
      Education students, but this relation was not gender-sensitive. More studies and
      research are needed to study and describe these variables according to gender
      from other perspectives. One proposal is to investigate the association between
      gender identity and self-efficacy and social skills and emotional intelligence to
      better understand how these constructs participate in adolescent development.

PMID- 28750268
TI  - Changes in severity of psychosocial difficulties in adolescents accessing
      specialist mental healthcare in England (2009-2014).
AB  - In England, clinicians and professional organisations report that higher numbers
      of adolescents with more severe psychosocial difficulties are accessing
      specialist services. A lack of national data on patterns of access to specialist
      services means there is limited information to inform policy. We examined whether
      severity of psychosocial difficulties in adolescents accessing mental healthcare
      has changed over time. Adolescents seen in specialist child mental healthcare in
      2009 vs. 2014 were matched on demographics and problem types using propensity
      score matching; final sample N = 2776 adolescents. We found: 1) stability over
      time in overall severity of difficulties, 2) an increase in severity of young
      women's emotional problems, and 3) a decrease in adolescents' conduct problems.
      The findings suggest the intriguing possibility that the criteria for accessing
      mental healthcare are not universally rising, but rather the patterns in access
      to specialist services may mirror epidemiological changes in severity of
      psychosocial difficulties in the population.

PMID- 28750269
TI  - A comparative analysis of ante- and postnatal clinical characteristics of
      extremely premature neonates suffering from refractory and non-refractory
      hypotension: Is early clinical differentiation possible?
AB  - BACKGROUND: About 25% of hypotensive ELBW infants are refractory to intravascular
      volume expansion and inotropic drugs (VI) and require hydrocortisone (HC). Such
      neonates suffer from complications of prolonged hypotension and extended therapy
      with VI. ELBW infants with refractory hypotension (RH) are clinically and
      biochemically indistinguishable from those who respond to VI. OBJECTIVE: Early
      identification and differentiation of ELBW infants susceptible to steroid
      dependent hypotension from those who respond to inotropic medications. METHODS:
      In a retrospective study the ante- and postnatal clinical characteristics of ELBW
      infants who received hydrocortisone (HC) for refractory hypotension (RH) were
      compared to those who responded to volume-inotropes (VI). RESULTS: Infants in HC
      group had lower birth weight (BW, 675+/-121g) and gestational age (GA, 25.1+/
      1.3weeks) and higher mean airway pressure and oxygen requirements, all
      independent of antenatal steroid (ANS) exposure. The receipt of ANS (p 0.01) and
      occurrences of maternal diabetes mellitus (GDM, p 0.01) were lower in HC group.
      ANS (OR 0.5, 95% CI 0.2-0.9, p 0.01) and GDM (OR 0.3, 95% CI 0.09-0.9, p 0.04)
      reduced the risk for RH. HC group had higher risk for IVH (OR 2.1, 95% CI 1.02
      4.2 p=0.04) which declined in the multivariate analysis. A trend towards lower
      risk of ventriculomegaly (VM) was noted in HC group (OR 0.3, 95% CI 0.1-1.1),
      which became significant after controlling for BW (OR 0.2 95% CI 0.07-0.9, p
      0.04). Similar trend was noted for maternal hypertension. CONCLUSION: Hypotension
      in ELBW infants who are <=25wks of GA and unexposed to ANS and GDM is refractory
      to VI therapy. Such neonates may benefit from an initial therapy with, or earlier
      institution of hydrocortisone. The trend towards a higher risk for VM with VI
      therapy needs validation in future studies.

PMID- 28750270
TI  - The influence of food consistency on chewing rate and muscular work.
AB  - Food properties influence the parameters of the masticatory process, such as jaw
      movement, muscle activity and chewing rate. Firm foods will require more muscle
      activity than softer foods. However, the influence of food hardness on chewing
      rate is ambiguous as both slower and higher chewing rates have been reported for
      harder foods. Rheological characteristics of the food, such as plasticity and
      elasticity, may help to explain differences in chewing rate. The aim of our study
      was to determine the influence of food properties on chewing rate and muscular
      work in five phases of a chewing sequence. Eighty-four participants chewed on
      five foods, which strongly differed in consistency. Chewing gum was used as a
      reference food. The phase in the chewing sequence had a large significant effect
      on cycle duration for the five foods. A significant decrease in cycle duration at
      the beginning of chewing was followed by an increase in later phases, leading to
      U-shaped curves. Food type had a small effect on the average cycle duration.
      However, large significant differences in cycle duration were observed between
      the foods at the beginning of a chewing sequence. In that phase, the firm foods
      were chewed much slower than the soft foods. Muscular work was significantly
      influenced by both chewing phase and food type.

PMID- 28750271
TI  - Safety, tolerability and antitumour activity of LY2780301 (p70S6K/AKT inhibitor)
      in combination with gemcitabine in molecularly selected patients with advanced or
      metastatic cancer: a phase IB dose escalation study.
AB  - BACKGROUND: LY2780301, a dual inhibitor of protein kinase B (AKT) and the
      downstream effector p70 ribosomal protein S6 kinase (p70S6K), may inhibit
      progression in tumours relying on phosphatidylinositol 3-kinase
      (PI3K)/AKT/mammalian target of rapamycin (mTOR) signalling pathway activation.
      This phase IB trial investigated the maximum tolerated dose (MTD), dose-limiting
      toxicities (DLTs), safety, pharmacokinetics (PK) and antitumour activity of
      LY2780301 plus gemcitabine in patients with advanced/metastatic solid tumours.
      METHODS: This was a non-randomised, open-label, dose escalation and dose
      expansion trial. Patients harbouring molecular alterations of the PI3K/AKT/mTOR
      pathway received once daily (QD) oral LY2780301 (400 or 500 mg) in combination
      with intravenous gemcitabine (750 or 1000 mg/m2) on days 1, 8 and 15 of a 28-d
      cycle. Dose escalation followed a 3 + 3 design. Assessments included adverse
      events (AEs), PK and preliminary antitumour activity. RESULTS: Fifty patients
      (median age, 53 years; 74% female) predominantly with mutations/amplifications of
      PI3K (60%) and phosphatase and tensin homologue (PTEN) gene/protein inactivation
      (42%) were treated for up to 14 cycles. The MTD was LY2780301 500 mg QD with
      gemcitabine 750 mg/m2. DLTs during cycle 1 were grade IV thrombocytopenia, grade
      III skin rash and grade III increase in alkaline phosphatase, gamma
      glutamyltransferase and alanine aminotransferase, occurring in one patient each.
      Most common AEs were anaemia (84%), fatigue (84%), transaminase increase (74%),
      thrombocytopenia (74%), nausea/vomiting (70%), neutropenia (68%) and lymphopenia
      (56%). Among the efficacy-evaluable population, two patients (5%) had a partial
      response; the disease control rate was 74% at cycle 2. CONCLUSIONS: Addition of
      LY2780301 to gemcitabine showed manageable toxicity and encouraging antitumour
      activity in patients with molecular alterations of the PI3K/AKT/mTOR pathway.
      CLINICAL TRIAL REGISTRATION NUMBER: NCT02018874.

PMID- 28750272
TI  - Medication use and kidney cancer risk: A population-based study.
AB  - BACKGROUND: Exposure to commonly prescribed medications may be associated with
      cancer risk. However, there is limited data in kidney cancer. Furthermore,
      methods of classifying cumulative medication exposure in previous studies may be
      prone to bias. METHODS: We conducted a population-based case-control study of
      10,377 incident kidney cancer cases aged >=66 years matched with 35,939 controls
      on age, sex, history of hypertension, comorbidity score, and geographic location.
      Cumulative exposure to commonly prescribed medications hypothesised to modulate
      cancer risk was obtained using prescription claims data. We modelled exposure in
      four different fashions: (1) as continuous exposures using (a) fractional
      polynomials (which allow for a non-linear relationship between an exposure and
      outcome) or (b) assuming linear relationships; and 2) as dichotomous exposures
      denoting (a) >=3 years versus <3 years exposure; or (b) "ever" versus "never"
      exposure. We used conditional logistic regression to estimate the association of
      medication exposure on incident kidney cancer. RESULTS: The directions of
      association were relatively consistent across analyses; however, the magnitudes
      were sensitive to the method of analysis. When utilising fractional polynomials,
      increasing cumulative exposure to acetylsalicylic acid, selective serotonin
      reuptake inhibitors, and proton-pump inhibitors was associated with significantly
      reduced risk of kidney cancer, while increasing exposure to antihypertensive
      drugs was associated with significantly increased risk. CONCLUSIONS: Our study
      provides impetus to further explore the effect of commonly prescribed medications
      on carcinogenesis to identify modifiable pharmacological interventions to reduce
      the risk of kidney cancer.

PMID- 28750273
TI  - Prognostic value of the G8 and modified-G8 screening tools for multidimensional
      health problems in older patients with cancer.
AB  - BACKGROUND: The G8 screening tool has been developed to identify older cancer
      patients requiring a geriatric assessment for tailoring therapy. Little is known
      about its prognostic value, particularly by tumour site. An optimised version has
      been recently developed, but no prognostic information is available. We compared
      the prognostic value of both instruments overall and by tumour site. METHODS:
      Data were from a prospective cohort of cancer patients >=70 years old referred to
      1 of 6 French geriatric oncology clinics between 2007 and 2014 (n = 1333).
      Endpoints were overall 1- and 3-year survival. Cox proportional-hazards models
      were built to assess the predictive value of abnormal G8 and modified-G8 scores,
      based on published cut-offs or by classes of increasing risk. Sensitivity
      analyses involved adjusting for age, gender, treatment, metastasis, and tumour
      site (digestive, breast, urinary tract, prostate, other solid cancers, and
      haematological malignancies) and stratifying by tumour site and metastatic
      status. RESULTS: Abnormal scores were independently associated with overall 1
      year survival: adjusted hazard ratio [aHR] = 4.3[G8]/4.9[modified-G8] and 3-year
      survival: aHR = 2.9/2.6; all p <0.0001. Associations persisted after stratifying
      by metastatic status and in most cancer sites (exceptions: colorectal (G8) and
      upper digestive cancer (both tools) [1-year analysis]; digestive cancers (both
      tools) [3-year analysis]). For both tools, classes of increasing risk showed a
      graded relationship with mortality (p < 0.0001). CONCLUSIONS: Our results
      identified both abnormal G8 and modified-G8 scores as strong and consistent
      predictors of overall survival, regardless of metastatic status or tumour site.
      These findings strengthen the clinical utility of these instruments in the
      geriatric oncology setting.

PMID- 28750274
TI  - Medical treatment of advanced chordomas.
AB  - Chordoma is a very rare bone sarcoma that can arise from any site along the spine
      and from the skull base. En bloc resection is the gold standard for treatment
      while radiation therapy has been shown to provide both curative and palliative
      benefit. Unfortunately, local recurrences are common, even after a complete
      surgical resection, and up to 40% of patients suffer from distant metastases,
      while salvage treatments are challenging. Patients carrying an advanced disease
      need a systemic treatment. Unluckily, conventional chordoma are insensitive to
      cytotoxic chemotherapy that is considered the standard treatment option in
      patients with metastatic sarcoma. In the last decade, innovative therapies have
      been introduced, positively impacting disease control and patients' quality of
      life. In addition, a better understanding of the molecular characteristics of
      chordoma allowed to detect new potential targets. This review is focused on the
      pharmacological management of patients affected by an advanced disease, starting
      with a summary of data available on conventional chemotherapy, then moving to a
      deeper analysis of available data on molecular agents and immunotherapy, and
      finally providing an update on ongoing clinical trials and future prospective.

PMID- 28750275
TI  - Special attention to women experiencing high-risk pregnancy: Delivery, care
      assistance and neonatal outcomes in two Brazilian maternity wards.
AB  - BACKGROUND: To compare two care models of high-risk pregnant women--a House for
      Pregnant Women, staffed by nurse-midwives, versus a traditional care model in a
      hospital maternity ward. DESIGN: This was across-sectional study conducted in two
      reference maternity hospitals for high-risk pregnancies, in Belo Horizonte, Minas
      Gerais, Brazil. The sample consisted of 312 high-risk pregnant women
      consecutively admitted from January 1st to December 31st, 2010, either to the
      House for Pregnant Women (n=247), or the hospital maternity ward (n=65).
      Gestational ages varied from 22 weeks to 36 weeks and six days. We measured
      individual, demographic, obstetric, labour and delivery variables, and newborn
      characteristics. For data analysis, we used descriptive, bivariate and
      multivariate statistics using Poisson regression, with a 5% significance level.
      FINDINGS: At the conventional hospital maternity ward, more women had six or more
      antenatal exams, greater frequencies of diagnosis related to blood pressure, and
      a greater number of women underwent either a C-section or a vaginal delivery with
      an episiotomy and analgesia. At the House for Pregnant Women, the majority of the
      hospitalizations were related to preterm labour and premature rupture of
      membranes. There were no statistical differences in the newborn characteristics.
      KEY CONCLUSIONS: The House for Pregnant Women care model, utilizing midwives was
      less interventionist, yet with results as favorable as in a conventional
      maternity hospital setting.

PMID- 28750276
TI  - Phylogenetic trends in the evolution of inflorescence odours in Amorphophallus.
AB  - The chemical composition of inflorescence odours of 80 species of Amorphophallus
      (Araceae) were determined by headspace-thermal desorption GC-MS. When compared to
      published molecular phylogenies of the genus, the data reveal evidence both of
      phylogenetic constraint and plasticity of odours. Dimethyl oligosulphides were
      found as common constituents of Amorphophallus odours and were the most abundant
      components in almost half of the species studied. Odours composed mainly of
      dimethyl oligosulphides, and perceived as being 'gaseous', were only found among
      Asian species, and some of these species clustered in certain clades in molecular
      phylogenies; e.g. in two clades in Amorphophallus subgenus Metandrium. However,
      some species with gaseous odours were found to be closely related to species
      producing odours more reminiscent of rotting meat in which various minor
      components accompany the dominant dimethyl oligosulphides. These two broad types
      of odours have co-evolved with other inflorescence characteristics such as
      colour, with species with rotting meat odours having darker inflorescences.
      Species producing pleasant odours characterised by benzenoid compounds constitute
      two broad groups that are not related in published phylogenies. Species having
      fruity odours containing 1-phenylethanol derivatives mainly occur in a clade in
      subgenus Metandrium while those with anise odours composed almost solely of the 2
      phenylethanol derivative 4-methoxyphenethyl alcohol are restricted to a clade in
      subgenus Scutandrium. Phylogenetic mapping of odours also indicates that the
      evolution of some odour types is likely to have been influenced by ecological
      factors. For example, species producing fishy odours dominated by trimethylamine
      and occurring in N and NE Borneo are not all closely related. Conversely, two
      sister species, A. mossambicensis and A. abyssinicus, which are morphologically
      very similar and have overlapping geographical distribution, produce odours which
      are very different chemically. The pressure of pollinator resource has therefore
      been a factor influencing the evolution of odours in Amorphophallus, driving both
      the divergence of odour types in some taxa and the convergence of odour types in
      others.

PMID- 28750277
TI  - Familial liability to psychosis is a risk factor for multimorbidity in people
      with psychotic disorders and their unaffected siblings.
AB  - BACKGROUND: Multimorbidity may impose an overwhelming burden on patients with
      psychosis and is affected by gender and age. Our aim is to study the independent
      role of familial liability to psychosis as a risk factor for multimorbidity.
      METHODS: We performed the study within the framework of the Genetic Risk and
      Outcome of Psychosis (GROUP) project. Overall, we compared 1024 psychotic
      patients, 994 unaffected siblings and 566 controls on the prevalence of 125
      lifetime diseases, and 19 self-reported somatic complaints. Multimorbidity was
      defined as the presence of two or more complaints/diseases in the same
      individual. Generalized linear mixed model (GLMM) were used to investigate the
      effects of gender, age (adolescent, young, older) and familial liability
      (patients, siblings, controls) and their interactions on multimorbidity. RESULTS:
      Familial liability had a significant effect on multimorbidity of either
      complaints or diseases. Patients had a higher prevalence of multimorbidity of
      complaints compared to siblings (OR 2.20, 95% CI 1.79-2.69, P<0.001) and to
      controls (3.05, 2.35-3.96, P<0.001). In physical health multimorbidity, patients
      (OR 1.36, 95% CI 1.05-1.75, P=0.018), but not siblings, had significantly higher
      prevalence than controls. Similar finding were observed for multimorbidity of
      lifetime diseases, including psychiatric diseases. Significant results were
      observed for complaints and disease multimorbidity across gender and age groups.
      CONCLUSION: Multimorbidity is a common burden, significantly more prevalent in
      patients and their unaffected siblings. Familial liability to psychosis showed an
      independent effect on multimorbidity; gender and age are also important factors
      determining multimorbidity.

PMID- 28750278
TI  - Neuropsychological deficits in adults age 60 and above with attention deficit
      hyperactivity disorder.
AB  - OBJECTIVE: Neuropsychological deficits are of major importance in ADHD, yet no
      previous studies have assessed clinically referred samples of older adults. The
      authors compared older adults with ADHD (60-75years) with both younger adults
      with ADHD (18-45years) and older healthy controls with regard to various
      neuropsychological deficits. METHODS: Well-established tests were used to
      investigate working memory, inhibition, switching, planning, fluency, and speed
      of processing. Self-ratings of executive functioning and delay-related behaviors
      were also included. Both variable-oriented and person-oriented analyses were
      conducted. RESULTS: Older adults with ADHD differed from controls with regard to
      working memory, inhibition, switching, and delay-related behaviors. In comparison
      to younger adults with ADHD, they performed at a similar level with regard to
      working memory and planning, but significantly better with regard to inhibition,
      switching, fluency, speed of processing, and delay aversion. Despite several
      significant group differences relative to controls, person-oriented analyses
      demonstrated that a majority of older adults with ADHD performed within the
      average range on each test and 20% showed no clear deficit within any
      neuropsychological domain. CONCLUSIONS: The results are in line with models of
      heterogeneity that have identified different neuropsychological subtypes in ADHD
      as well as a subgroup of patients without any clear neuropsychological deficits.
      For older adults with ADHD, it will be important to assess their functioning
      across time as normal aging is related to memory decline and these patients could
      therefore end up with severe deficits as they grow older, which in turn could
      have serious negative effects on daily life functioning.

PMID- 28750279
TI  - TNF-receptor superfamily agonists as molecular adjuvants for cancer vaccines.
AB  - Cancer vaccines have offered unrequited hope as a mechanism for rapidly and
      potently eliciting a patient's immune system to counter tumors. Initial results
      from preclinical mouse models have not translated to substantial benefit to
      patients, suggesting that either the targets or the vaccination approach were
      inadequate. Recent innovations in antigen identification have spiked renewed
      interest vaccination technologies. This has coincided with a detailed molecular
      understanding of the coordinated steps in postactivation support of T cell
      proliferation, differentiation and survival, leading to the development of novel
      targets and combinations that are substantially more effective than first and
      second generation cancer vaccines in preclinical models. Within this cluster of
      developments, the TNF-receptor superfamily members have emerged as attractive
      candidates for clinical implementation. Here we review recent developments in the
      mechanisms of action of TNFRSF agonists, and how their activity is potentiated by
      integration co-targeting pattern recognition receptors.

PMID- 28750281
TI  - Heteroleptic monometallic and trimetallic ruthenium(II) complexes incorporating a
      pi-extended dipyrrin ligand: Light-activated reactions with the A549 lung cancer
      cell line.
AB  - A heteroleptic monometallic ruthenium(II) and a heteroleptic trimetallic
      ruthenium(II) complex have been synthesized and characterized. Both complexes
      have an overall 3+ charge, with the charge density greater for the monometallic
      complex. The electronic spectra of the monometallic ruthenium(II) complex
      exhibits intense pi-pi* transitions associated with the bipyridyl groups along
      with overlapping metal to ligand charge transfer (MLCT) and ligand centered pi
      pi* transitions ranging from 520nm to approximately 600nm. The trimetallic
      ruthenium(II) complex, on the other hand, displays more well defined transitions
      with the expected pi-pi* transition of the bipyridyl groups at 294nm and Ru(dpi)
      to bpy(pi*) MLCT transitions at 355nm and 502nm. In addition to these absorption
      bands an intense transition, 578nm, resulting from overlapping dipyrrin (pi-pi*)
      and Ru(dpi) to dipyrrin(pi*) transitions is observed. Electrochemical and
      spectroelectrochemical experiments were used to help in assigning these
      transitions. Irradiation of the complexes in the presence of plasmid DNA within
      the photodynamic therapy window (600nm to 850nm) reveal, using electrophoresis,
      that both complexes are capable of causing photo-damage to the DNA backbone. The
      trimetallic ruthenium(II) complex; however, also shows the ability to generate
      photoinduced DNA damage in the absence of oxygen, suggesting a photo-oxidative
      process. Studies of the complexes toward lung cancer cells (A549 cell line) in
      the absence of light indicate little cytotoxicity up to 50MUM. Upon irradiation
      of the cells with a low power 420nm light source the trimetallic complex showed
      considerably greater photo-cytotoxicity compared to the monometallic analog. A
      dose-dependent response curve gives an IC50 of 92MUM for complex B.

PMID- 28750280
TI  - Tuberculosis vaccines - perspectives from the NIH/NIAID Mycobacteria vaccine
      testing program.
AB  - The development of novel vaccine candidates against infections with Mycobacterium
      tuberculosis has highlighted our limited understanding of immune mechanisms
      required to kill M. tuberculosis. The induction of a Th1 immunity is vital, but
      new studies are required to identify other mechanisms that may be necessary.
      Novel vaccines formulations that invoke effector cells such as innate lymphoid
      cells may provide an environment that promote effector mechanisms including T
      cell and B cell mediated immunity. Identifying pathways associated with killing
      this highly successful infectious agent has become critical to achieving the goal
      of reducing the global tuberculosis burden.

PMID- 28750282
TI  - Design and reactivity of Ni-complexes using pentadentate neutral-polypyridyl
      ligands: Possible mimics of NiSOD.
AB  - Superoxide plays a key role in cell signaling, but can be cytotoxic within cells
      unless well regulated by enzymes known as superoxide dismutases (SOD). Nickel
      superoxide dismutase (NiSOD) catalyzes the disproportion of the harmful
      superoxide radical into hydrogen peroxide and dioxygen. NiSOD has a unique active
      site structure that plays an important role in tuning the potential of the nickel
      center to function as an effective catalyst for superoxide dismutation with
      diffusion controlled rates. The synthesis of structural and functional analogues
      of NiSOD provides a route to better understand the role of the nickel active site
      in superoxide dismutation. In this work, the synthesis of a series of nickel
      complexes supported by nitrogen rich pentadentate ligands is reported. The
      complexes have been characterized through absorption spectroscopy, mass
      spectrometry, and elemental analysis. X-ray absorption spectroscopy was employed
      to establish the oxidation state and the coordination geometry around the metal
      center. The reactivity of these complexes toward KO2 was evaluated to elucidate
      the role of the coordination sphere in controlling superoxide dismutation
      reactivity.

PMID- 28750283
TI  - Evaluation of allocation methods for calculation of carbon footprint of grass
      based dairy production.
AB  - A major methodological issue for life cycle assessment, commonly used to quantify
      greenhouse gas emissions from livestock systems, is allocation from
      multifunctional processes. When a process produces more than one output, the
      environmental burden has to be assigned between the outputs, such as milk and
      meat from a dairy cow. In the absence of an objective function for choosing an
      allocation method, a decision must be made considering a range of factors, one of
      which is the availability and quality of necessary data. The objective of this
      study was to evaluate allocation methods to calculate the climate change impact
      of the economically average (?/ha) dairy farm in Ireland considering both milk
      and meat outputs, focusing specifically on the pedigree of the available data for
      each method. The methods were: economic, energy, protein, emergy, mass of
      liveweight, mass of carcass weight and physical causality. The data quality for
      each method was expressed using a pedigree score based on reliability of the
      source, completeness, temporal applicability, geographical alignment and
      technological appropriateness. Scenario analysis was used to compare the
      normalised impact per functional unit (FU) from the different allocation methods,
      between the best and worst third of farms (in economic terms, ?/ha) in the
      national farm survey. For the average farm, the allocation factors for milk
      ranged from 75% (physical causality) to 89% (mass of carcass weight), which in
      turn resulted in an impact per FU, from 1.04 to 1.22 kg CO2-eq/kg (fat and
      protein corrected milk). Pedigree scores ranged from 6.0 to 17.1 with protein and
      economic allocation having the best pedigree. It was concluded that when making
      the choice of allocation method, the quality of the data available (pedigree)
      should be given greater emphasis during the decision making process because the
      effect of allocation on the results. A range of allocation methods could be
      deployed to understand the uncertainty associated with the decision.

PMID- 28750284
TI  - Reviewing Bayesian Networks potentials for climate change impacts assessment and
      management: A multi-risk perspective.
AB  - The evaluation and management of climate change impacts on natural and human
      systems required the adoption of a multi-risk perspective in which the effect of
      multiple stressors, processes and interconnections are simultaneously modelled.
      Despite Bayesian Networks (BNs) are popular integrated modelling tools to deal
      with uncertain and complex domains, their application in the context of climate
      change still represent a limited explored field. The paper, drawing on the review
      of existing applications in the field of environmental management, discusses the
      potential and limitation of applying BNs to improve current climate change risk
      assessment procedures. Main potentials include the advantage to consider multiple
      stressors and endpoints in the same framework, their flexibility in dealing and
      communicate with the uncertainty of climate projections and the opportunity to
      perform scenario analysis. Some limitations (i.e. representation of temporal and
      spatial dynamics, quantitative validation), however, should be overcome to boost
      BNs use in climate change impacts assessment and management.

PMID- 28750285
TI  - Modelling food-web mediated effects of hydrological variability and environmental
      flows.
AB  - Environmental flows are designed to enhance aquatic ecosystems through a variety
      of mechanisms; however, to date most attention has been paid to the effects on
      habitat quality and life-history triggers, especially for fish and vegetation.
      The effects of environmental flows on food webs have so far received little
      attention, despite food-web thinking being fundamental to understanding of river
      ecosystems. Understanding environmental flows in a food-web context can help
      scientists and policy-makers better understand and manage outcomes of flow
      alteration and restoration. In this paper, we consider mechanisms by which flow
      variability can influence and alter food webs, and place these within a
      conceptual and numerical modelling framework. We also review the strengths and
      weaknesses of various approaches to modelling the effects of hydrological
      management on food webs. Although classic bioenergetic models such as Ecopath
      with Ecosim capture many of the key features required, other approaches, such as
      biogeochemical ecosystem modelling, end-to-end modelling, population dynamic
      models, individual-based models, graph theory models, and stock assessment models
      are also relevant. In many cases, a combination of approaches will be useful. We
      identify current challenges and new directions in modelling food-web responses to
      hydrological variability and environmental flow management. These include better
      integration of food-web and hydraulic models, taking physiologically-based
      approaches to food quality effects, and better representation of variations in
      space and time that may create ecosystem control points.

PMID- 28750286
TI  - Short-term forecasting of turbidity in trunk main networks.
AB  - Water discolouration is an increasingly important and expensive issue due to
      rising customer expectations, tighter regulatory demands and ageing Water
      Distribution Systems (WDSs) in the UK and abroad. This paper presents a new
      turbidity forecasting methodology capable of aiding operational staff and
      enabling proactive management strategies. The turbidity forecasting methodology
      developed here is completely data-driven and does not require hydraulic or water
      quality network model that is expensive to build and maintain. The methodology is
      tested and verified on a real trunk main network with observed turbidity
      measurement data. Results obtained show that the methodology can detect if
      discolouration material is mobilised, estimate if sufficient turbidity will be
      generated to exceed a preselected threshold and approximate how long the material
      will take to reach the downstream meter. Classification based forecasts of
      turbidity can be reliably made up to 5 h ahead although at the expense of
      increased false alarm rates. The methodology presented here could be used as an
      early warning system that can enable a multitude of cost beneficial proactive
      management strategies to be implemented as an alternative to expensive trunk
      mains cleaning programs.

PMID- 28750287
TI  - Operation-driven heterogeneity and overlooked feed-associated populations in
      global anaerobic digester microbiome.
AB  - Anaerobic digester (AD) microbiomes harbor complex, interacting microbial
      populations to achieve biomass reduction and biogas production, however how they
      are influenced by operating conditions and feed sludge microorganisms remain
      unclear. These were addressed by analyzing the microbial communities of 90 full
      scale digesters at 51 municipal wastewater treatment plants from five countries.
      Heterogeneity detected in community structures suggested that no single AD
      microbiome could be defined. Instead, the AD microbiomes were classified into
      eight clusters driven by operating conditions (e.g., pretreatment, temperature
      range, and salinity), whereas geographic location of the digesters did not have
      significant impacts. Comparing digesters populations with those present in the
      corresponding feed sludge led to the identification of a hitherto overlooked feed
      associated microbial group (i.e., the residue populations). They accounted for up
      to 21.4% of total sequences in ADs operated at low temperature, presumably due to
      ineffective digestion, and as low as 0.8% in ADs with pretreatment. Within each
      cluster, a core microbiome was defined, including methanogens, syntrophic
      metabolizers, fermenters, and the newly described residue populations. Our work
      provides insights into the key factors shaping full-scale AD microbiomes in a
      global scale, and draws attentions to the overlooked residue populations.

PMID- 28750288
TI  - Combining stable isotopes with contamination indicators: A method for improved
      investigation of nitrate sources and dynamics in aquifers with mixed nitrogen
      inputs.
AB  - Excessive nitrate (NO3-) concentration in groundwater raises health and
      environmental issues that must be addressed by all European Union (EU) member
      states under the Nitrates Directive and the Water Framework Directive. The
      identification of NO3- sources is critical to efficiently control or reverse NO3-
      contamination that affects many aquifers. In that respect, the use of stable
      isotope ratios 15N/14N and 18O/16O in NO3- (expressed as delta15N-NO3- and
      delta18O-NO3-, respectively) has long shown its value. However, limitations exist
      in complex environments where multiple nitrogen (N) sources coexist. This two
      year study explores a method for improved NO3- source investigation in a shallow
      unconfined aquifer with mixed N inputs and a long established NO3- problem. In
      this tillage-dominated area of free-draining soil and subsoil, suspected NO3-
      sources were diffuse applications of artificial fertiliser and organic point
      sources (septic tanks and farmyards). Bearing in mind that artificial diffuse
      sources were ubiquitous, groundwater samples were first classified according to a
      combination of two indicators relevant of point source contamination:
      presence/absence of organic point sources (i.e. septic tank and/or farmyard) near
      sampling wells and exceedance/non-exceedance of a contamination threshold value
      for sodium (Na+) in groundwater. This classification identified three
      contamination groups: agricultural diffuse source but no point source (D+P-),
      agricultural diffuse and point source (D+P+) and agricultural diffuse but point
      source occurrence ambiguous (D+P+/-). Thereafter delta15N-NO3- and delta18O-NO3-
      data were superimposed on the classification. As delta15N-NO3- was plotted
      against delta18O-NO3-, comparisons were made between the different contamination
      groups. Overall, both delta variables were significantly and positively
      correlated (p < 0.0001, rs = 0.599, slope of 0.5), which was indicative of
      denitrification. An inspection of the contamination groups revealed that
      denitrification did not occur in the absence of point source contamination (group
      D+P-). In fact, strong significant denitrification lines occurred only in the
      D+P+ and D+P+/- groups (p < 0.0001, rs > 0.6, 0.53 <= slope <= 0.76), i.e. where
      point source contamination was characterised or suspected. These lines originated
      from the 2-60/00 range for delta15N-NO3-, which suggests that i) NO3-
      contamination was dominated by an agricultural diffuse N source (most likely the
      large organic matter pool that has incorporated 15N-depleted nitrogen from
      artificial fertiliser in agricultural soils and whose nitrification is stimulated
      by ploughing and fertilisation) rather than point sources and ii) denitrification
      was possibly favoured by high dissolved organic content (DOC) from point sources.
      Combining contamination indicators and a large stable isotope dataset collected
      over a large study area could therefore improve our understanding of the NO3-
      contamination processes in groundwater for better land use management. We
      hypothesise that in future research, additional contamination indicators (e.g.
      pharmaceutical molecules) could also be combined to disentangle NO3-
      contamination from animal and human wastes.

PMID- 28750289
TI  - Activation of sodium persulfate by magnetic carbon xerogels (CX/CoFe) for the
      oxidation of bisphenol A: Process variables effects, matrix effects and reaction
      pathways.
AB  - An advanced oxidation process comprising sodium persulfate (SPS) and a novel
      magnetic carbon xerogel was tested for the degradation of bisphenol A (BPA), a
      model endocrine-disrupting compound. The catalyst, consisting of interconnected
      carbon microspheres with embedded iron and cobalt microparticles, was capable of
      activating persulfate to form sulfate and hydroxyl radicals at ambient
      conditions. The pseudo-first order degradation rate of BPA in ultrapure water
      (UPW) was found to increase with (i) increasing catalyst (25-75 mg/L) and SPS (31
      250 mg/L) concentrations, (ii) decreasing BPA concentration (285-14,200 MUg/L),
      and (iii) changing pH from alkaline to acidic values (9-3). Besides UPW, tests
      were conducted in drinking water, treated wastewater, groundwater and surface
      water; interestingly, the rate in UPW was always lower than in any other matrix
      containing several organic and inorganic constituents. The effect of natural
      organic matter (in the form of humic acids) and alcohols was detrimental to BPA
      degradation owing to the scavenging of radicals. Conversely, chlorides at
      concentrations greater than 50 mg/L had a positive effect due to the formation
      and subsequent participation of chlorine-containing radicals. Liquid
      chromatography time-of-flight mass spectrometry was employed to identify major
      transformation by-products (TBPs) of BPA degradation in the absence and presence
      of chlorides; in the latter case, several chlorinated TBPs were detected
      confirming the role of Cl-related radicals. Based on TBPs, main reaction pathways
      are proposed.

PMID- 28750290
TI  - High frequency activity overriding cortico-cortical evoked potentials reflects
      altered excitability in the human epileptic focus.
AB  - OBJECTIVE: We aimed to clarify that high frequency activity (HFA) of cortico
      cortical evoked potentials (CCEPs), elicited by single pulse electrical
      stimulation (SPES), reflects cortical excitability. METHODS: We recruited 16
      patients with refractory partial epilepsy who had chronic subdural electrode
      implantation for presurgical evaluation. A repetitive SPES was given to (1) the
      seizure onset zone (SOZ) and (2) the control cortices (non-seizure onset zone:
      nSOZ). CCEPs were recorded from the neighboring cortices within SOZ and nSOZ. We
      applied short-time Fourier transform to obtain the induced responses for the
      timing of early (<50ms after SPES) and late CCEP components and analyzed the
      logarithmic power change for ripple (<200Hz) and fast ripple (>200Hz) bands.
      RESULTS: Twenty-one clear CCEPs were recorded for both the SOZ and nSOZ. The HFA
      power of early CCEPs in SOZ significantly increased compared to that in nSOZ in
      both frequency bands, particularly in mesial temporal lobe epilepsy (MTLE).
      CONCLUSION: Similar to the features of spontaneous pathological HFOs, the power
      of stimulus-induced HFAs in SOZ were greater than that outside SOZ, particularly
      in MTLE. SIGNIFICANCE: HFA overriding CCEPs can be a surrogate marker of cortical
      excitability in epileptic focus.

PMID- 28750291
TI  - Structural characteristics of the core layer and biomimetic model of the ladybug
      forewing.
AB  - To explore the characteristics of the core structure of ladybug (Harmonia
      axyridis) forewings, their microstructure was studied using microscopes. The
      results suggest that trabeculae exist in the frame of the beetle (ladybug)
      forewing for the first time; this study represents the first determination of the
      parameters N, the total number of trabeculae in each forewing, and lambdat, the
      ratio of the cross-sectional area of the trabeculae to the effective area of
      trabecular distribution. The cross-sectional area of a single trabecula in the
      ladybug forewing is smaller than those in two other kinds of beetles, Allomyrina
      dichotoma and Prosopocoilus inclinatus. However, the average trabecular density
      of the ladybug forewing is 84 per square millimeter, which is the highest among
      these three kinds of beetles. The lambdat values are 1.0%, 1.5% and 10.5% for H.
      axyridis, A. dichotoma and P. inclinatus, respectively, and the corresponding N
      values are approximately 1.4, 1.7 and 3.7 thousand, respectively. Based on these
      findings, a biomimetic model of the ladybug forewing is proposed, which is
      characterized by a core structure with a high-density distribution of thin
      trabeculae surrounded by a foam-like material.

PMID- 28750292
TI  - Cortisol boosts risky decision-making behavior in men but not in women.
AB  - Acute stress may escalate risky decision-making in men, while there is no such
      effect in women. Although first evidence links these gender-specific effects of
      stress to stress-induced changes in cortisol, whether elevated cortisol is indeed
      sufficient to boost risk-taking, whether a potential cortisol effect depends on
      simultaneous noradrenergic activation, and whether cortisol and noradrenergic
      activation exert distinct effects on risk-taking in men and women is unknown. In
      this experiment, we therefore set out to elucidate the impact of cortisol and
      noradrenergic stimulation on risky decision-making in men and women. In a fully
      crossed, placebo-controlled, double-blind design, male and female participants
      received orally either a placebo, hydrocortisone, yohimbine, an alpha-2
      adrenoceptor-antagonist leading to increased noradrenergic stimulation, or both
      drugs before completing the balloon analogue risk task, a validated measure of
      risk-taking. Overall, participants' choice was risk-sensitive as reflected in
      reduced responding in high- compared to moderate- and low-risk conditions.
      Cortisol, however, led to a striking increase in risk-taking in men, whereas it
      had no effect on risk-taking behavior in women. Yohimbine had no such effect and
      the gender-specific effect of cortisol was not modulated by yohimbine. Our data
      show that cortisol boosts risk-taking behavior in men but not in women. This
      differential effect of cortisol on risk-taking may drive gender differences in
      risky decision-making under stress.

PMID- 28750293
TI  - Effects of polystyrene microbeads in marine planktonic crustaceans.
AB  - Plastic debris accumulates in the marine environment, fragmenting into
      microplastics (MP), causing concern about their potential toxic effects when
      ingested by marine organisms. The aim of this study was to verify whether 0.1um
      polystyrene beads are likely to trigger lethal and sub-lethal responses in marine
      planktonic crustaceans. MP build-up, mortality, swimming speed alteration and
      enzyme activity (cholinesterases, catalase) were investigated in the larval
      stages of Amphibalanus amphitrite barnacle and of Artemia franciscana brine
      shrimp exposed to a wide range of MP concentrations (from 0.001 to 10mgL-1) for
      24 and 48h. The results show that MP were accumulated in crustaceans, without
      affecting mortality. Swimming activity was significantly altered in crustaceans
      exposed to high MP concentrations (> 1mgL-1) after 48h. Enzyme activities were
      significantly affected in all organisms exposed to all the above MP
      concentrations, indicating that neurotoxic effects and oxidative stress were
      induced after MP treatment. These findings provide new insight into sub-lethal MP
      effects on marine crustaceans.

PMID- 28750294
TI  - Freezability genetics in rabbit semen.
AB  - The aim of this study was to estimate the heritability of semen freezability and
      to estimate the genetic correlation between frozen-thawed sperm traits and the
      growth rate in a paternal rabbit line. Estimated heritabilities showed that
      frozen-thawed semen traits are heritable (ranged between 0.08 and 0.15). In the
      case of Live-FT (percentage of viable sperm after freezing), the estimated
      heritability is the highest one, and suggests the possibility of effective
      selection. After the study of genetic correlations it seems that daily weight
      gain (DG) was negatively correlated with sperm freezability, but no further
      conclusions could be drawn due to the high HPD95%. More data should be included
      in order to obtain better accuracy for the estimates of these genetic
      correlations. If the results obtained at present study were confirmed, it would
      imply that selection for DG could alter sperm cell membranes or seminal plasma
      composition, both components related to sperm cryoresistance.

PMID- 28750295
TI  - Effect of zearalenone on circulating testosterone concentration, testicular and
      epididymal morphology and epididymal sperm characteristics in wild boars.
AB  - This study investigated the effect of exposure to zearalenone (ZEN) and its
      metabolites on the characteristics of epididymal spermatozoa, testicular and
      epididymal biometry and histology, and the concentration of testosterone in blood
      plasma in male wild boars. The study was performed during more than one year on
      18 clinically healthy male wild boars with initial and final body weight, of 39
      +/- 4 kg and 59 +/- 3 kg, respectively. The animals were divided into two
      experimental groups (group I and group II) and one control group (group C)
      comprising 6 boars per group. Group I animals were administered per os pure
      zearalenone (ZEN) at 150 MUg/kg BW for 7 consecutive days every two months, while
      group II animals received a dose of 50 MUg/kg BW/day via feed that was naturally
      contaminated with ZEN. These male wild boars were exposed to ZEN over a period of
      1 year. Control animals were fed a placebo. Testicles with epididymides of the
      boars were collected on the last day of the experiment within 3 min after
      slaughter. Blood samples were collected from each of the male wild boars. Testes
      and epididymides were measured and sampled for histological examination.
      Epididymides were dissected and epididymal spermatozoa were harvested. The
      spermatozoa were diluted with swine-specific BTS extender and stored at 17
      degrees C for 144 h. Sperm motility was analyzed with CASA, and other parameters
      including viability, acrosome integrity, DNA fragmentation index, lipid
      peroxidation and apoptosis were assessed with flow cytometry. In these wild
      boars, per os exposure to natural sources of ZEN or a combination of ZEN and its
      metabolites changed the testicular interstitium and led to modification of some
      epididymal sperm parameters. The interstitial glands in testes of experimental
      group I were markedly reduced and hyperemic with evident blood stasis in small
      capillaries. Also in group I were single degenerating seminiferous tubules. In
      both groups I and II, immediately after dilution of spermatozoa with BTS
      remarkable decreases in motility rate as well as in progressive motility and the
      subpopulation of cells with rapid movement were noted compared with the control
      group (P < 0.05). But unexpectedly, after 24 h incubation of boar semen in the
      BTS diluent, these sperm properties improved and were not significantly different
      from the control group. Thus, exposure to ZEN has no lasting but only a
      temporary, reversible effect on wild boar sperm motility. There was no influence
      of exposure to ZEN and its metabolites on the integrity of membranes, intensity
      of lipid peroxidation and apoptosis or on sperm chromatin structure. This study
      is the first using these direct measures of sperm motility and integrity to show
      a redundant adverse effect of ZEN exposure on wild boar sperm characteristics.
      There were no effects of exposure to ZEN and its metabolites on body weight,
      testicular and epididymal biometry, gonadosomatic index and the concentration of
      testosterone in blood plasma in the male wild boars.

PMID- 28750296
TI  - The role of L-type calcium channels in mouse oocyte maturation, activation and
      early embryonic development.
AB  - Calcium ion fluctuation is closely related to the transformation of cell cycle.
      However, little is known about the function of L-type calcium channel in
      mammalian oocyte and embryo development. We thus studied the roles of L-type
      calcium channel in mouse oocyte meiotic maturation, parthenogenetic activation
      and early embryonic development. We used the antagonist Amlodipine to block L
      type calcium channel. Oocytes or zygotes were cultured to different time points
      with 0 MUM, 10 MUM, 30 MUM and 50 MUM Amlodipine. Then we checked the rate of
      first polar body extrusion, spindle formation, asymmetric division
      parthenogenetic activation and early embryo cleavage. The results showed that
      Amlodipine treatment did not affect germinal vesicle breakdown, but caused
      disruption of cytoskeleton organization, symmetric division, formation of mature
      oocytes with a large polar body, or reduced the first polar body extrusion,
      depending on its concentrations. Amlodipine treatment also resulted in decreased
      parthenogenetic activation and arrested early embryonic development. Overall,
      these data suggest that proper function of L-type calcium channel is critical for
      oocyte maturation, activation, and early embryonic development.

PMID- 28750297
TI  - Fertility and pregnancy issues in BRCA-mutated breast cancer patients.
AB  - Fertility and pregnancy-related issues represent one of the main areas of
      concerns for young women with breast cancer. Carrying a germline deleterious BRCA
      mutation adds additional burden on this regard due to the specific issues that
      should be considered during the oncofertility counseling of this special patient
      group. Despite the availability of a growing amount of data in the general breast
      cancer population on the feasibility and safety of fertility preservation and
      pregnancy after diagnosis, numerous challenges remain for BRCA-mutated breast
      cancer patients in whom very limited studies have been performed so far.
      Therefore, studies aiming to address the specific issues of these patients,
      including the impact of the mutation on their fertility potential, the safety and
      efficacy of the different strategies for fertility preservation, and the
      feasibility of having a pregnancy after diagnosis, should be considered a
      research priority. The aim of the present manuscript is to perform an in depth
      overview on the role of BRCA mutations in breast cancer with a specific focus on
      their impact on reproductive potential, and to discuss the fertility and
      pregnancy issues faced by BRCA-mutated breast cancer patients. The final goal of
      this manuscript is to highlight current and upcoming knowledge in this field for
      trying to help physicians dealing with these patients during oncofertility
      counseling.

PMID- 28750298
TI  - Global gene expression changes of amniotic fluid cell free RNA according to fetal
      development.
AB  - OBJECTIVE: This study aimed to evaluate the effect of in utero fetal development
      on the cell-free transcriptome of amniotic fluid by analyzing global gene
      expression in the amniotic fluid supernatant obtained at different gestational
      ages from euploid fetuses STUDY DESIGN: Thirteen amniotic fluid samples were
      obtained from five individuals at 28 gestational weeks and eight individuals at
      full term pregnancy. Transcriptome data previously analyzed by our group from 14
      euploid mid-trimester amniotic fluid samples were used for comparative analysis.
      RNA was extracted from amniotic fluid supernatants, hybridized to Affymetrix
      GeneChip Human arrays, and the transcriptome was analyzed using the DAVID
      toolkit. RESULTS: We evaluated 27 samples, which were divided into three groups
      as follows: 14 subjects between 16 and 18 gestational weeks from our previous
      study (group 1), five subjects in late second trimester (group 2), and eight
      subjects at full term pregnancy (group 3). No genes were significantly
      differentially regulated between group 3 and group 2. We identified 545 probe
      sets that were significantly differentially expressed between group 1 and group 2
      and 3 samples (FDR P-value <0.05). Based on tissue expression analysis, 396 genes
      that were upregulated in group 1 were enriched in the nervous system including
      brain and endocrine organs such as pancreas and adrenal gland. In addition, 136
      genes that were upregulated in group 2 and 3 were specific to bronchioepithelial
      cells. Functional pathway analysis revealed that there was no significantly
      enriched pathway in terms of genes that were upregulated in either group 2 or
      group 3. Comparing the amniotic fluid cell-free transcriptome of group 1 and 2
      with that of group 3, 18 genes were significantly differently modulated.
      CONCLUSIONS: Fetal development affects the amniotic fluid cell-free
      transcriptome. Fetal skin keratinization, which begins at 19 gestational weeks,
      might play an important role in changes in global gene expression in the amniotic
      fluid.

PMID- 28750299
TI  - Prolonged activation of the coagulation system during in vitro fertilization
      cycles.
AB  - OBJECTIVE: To investigate coagulation system changes during an in-vitro
      fertilization (IVF) cycle using Thromboelastogram (TEG) that enables analysis of
      the elastic properties of whole blood samples and provides a global assessment of
      the hemostatic function. STUDY DESIGN: A prospective study. TEG indices were
      evaluated in 23 women who underwent controlled ovarian stimulation for IVF at
      four points in time: 1. At the beginning of the cycle (corresponding to the
      lowest levels of E2), 2. On the day of hCG administration (maximal stimulation
      with highest E2 levels), 3. On the day of ovum pickup and 4. At the first
      pregnancy test (approximately 14days after ovum pickup). The main outcome
      measures were TEG indices including R-time (time until initial fibrin formation),
      K-time (time until a 20mm amplitude is achieved), alpha angle (the rate of clot
      formation), Maximum Amplitude (MA, strength of the fibrin clot), Coagulation
      Index (CI, calculated overall indicator of coagulation) and LY30 (the decrease in
      graph amplitude). RESULTS: R, K, alpha angle, MA and CI before hCG administration
      and at the time of the first pregnancy test were significantly higher compared to
      the baseline measurement before gonadotropins administration. No correlation was
      found between E2 and TEG indices. CONCLUSION: Ovarian stimulation is associated
      with prolonged increased coagulability that extends after the time of maximal
      ovarian stimulation. The lack of association between E2 levels and TEG indices
      suggest that additional factors may play a role in the pathogenesis of increased
      coagulability in women with ovarian stimulation.

PMID- 28750300
TI  - Deterioration of the mechanical properties of calcium phosphate cements with Poly
      (gamma-glutamic acid) and its strontium salt after in vitro degradation.
AB  - The mechanical reliability of calcium phosphate cements has restricted their
      clinical application in load-bearing locations. Although their mechanical
      strength can be improved using a variety of strategies, their fatigue properties
      are still unclear, especially after degradation. The evolutions of uniaxial
      compressive properties and the fatigue behavior of calcium phosphate cements
      incorporating poly (gamma-glutamic acid) and its strontium salt after different
      in vitro degradation times were investigated in the present study. Compressive
      strength decreased from the 61.2+/-5.4MPa of the original specimen, to 51.1+/
      4.4, 42.2+/-3.8, 36.8+/-2.4 and 28.9+/-3.2MPa following degradation for one, two,
      three and four weeks, respectively. Fatigue life under same loading condition
      also decreased with increasing degradation time. The original specimens remained
      intact for one million cycles (run-out) under a maximum stress of 30MPa. After
      degradation for one to four weeks, the specimens were able to withstand maximum
      stress of 20, 15, 10 and 10MPa, respectively until run-out. Defect volume
      fraction within the specimens increased from 0.19+/-0.021% of the original
      specimen to 0.60+/-0.19%, 1.09+/-0.04%, 2.68+/-0.64% and 7.18+/-0.34% at
      degradation time of one, two, three and four weeks, respectively. Therefore, we
      can infer that the primary cause of the deterioration of the mechanical
      properties was an increasing in micro defects induced by degradation, which
      promoted crack initiation and propagation, accelerating the final mechanical
      failure of the bone cement. This study provided the data required for enhancing
      the mechanical reliability of the calcium phosphate cements after different
      degradation times, which will be significant for the modification of load-bearing
      biodegradable bone cements to match clinical application.

PMID- 28750302
TI  - Using developmental evaluation as a system of organizational learning: An example
      from San Francisco.
AB  - In the last 20 years, developmental evaluation has emerged as a promising
      approach to support organizational learning in emergent social programs. Through
      a continuous system of inquiry, reflection, and application of knowledge,
      developmental evaluation serves as a system of tools, methods, and guiding
      principles intended to support constructive organizational learning. However,
      missing from the developmental evaluation literature is a nuanced framework to
      guide evaluators in how to elevate the organizational practices and concepts most
      relevant for emergent programs. In this article, we describe and reflect on work
      we did to develop, pilot, and refine an integrated pilot framework. Drawing on
      established developmental evaluation inquiry frameworks and incorporating lessons
      learned from applying the pilot framework, we put forward the Evaluation-led
      Learning framework to help fill that gap and encourage others to implement and
      refine it. We posit that without explicitly incorporating the assessments at the
      foundation of the Evaluation-led Learning framework, developmental evaluation's
      ability to affect organizational learning in productive ways will likely be
      haphazard and limited.

PMID- 28750301
TI  - Titanium tetrafluoride incorporated into a two-step self-etching adhesive system:
      physico-mechanical characterization and bonding stability.
AB  - OBJECTIVES: To evaluate the influence of TiF4 incorporated into the primer (P) or
      bond (B) of a self-etching adhesive system on long-term dentin bonding, and
      evaluate the physico-mechanical properties of TiF4-containing adhesives. METHODS:
      Dentin surfaces received the following treatments (n = 8): CL (Clearfil SE Bond);
      TiF4CL (dentin pretreatment with TiF4 aqueous solution + CL); TiF4P (TiF4
      incorporated into the P); TiF4B (TiF4 incorporated into the B). Microtensile bond
      strength (uTBS) and failure mode evaluations were performed after 24h, 6 months
      and one year, respectively. Degree of conversion (DC) and flexural strength (FS)
      were evaluated to determine whether TiF4 influenced adhesive properties. Particle
      size (PS), polydispersity index (PI) and zeta potential (ZP) of TiF4-containing
      adhesives were measured using dynamic light scattering. Two-way ANOVA for
      repeated measures was applied to uTBS data, and one-way ANOVA and Tukey tests to
      DC and FS results. RESULTS: There was no difference in uTBS among the groups (p =
      0.818) regardless of time; the uTBS in each group was not significantly affected
      over time (p = 0.061). TiF4P and TiF4B significantly affected FS (p = 0.004). The
      DC for TiF4P was not significantly different from that of CL, and higher than
      that of TiF4B. Lower average particle size was observed for TiF4P at baseline.
      TiF4 aqueous solution showed a tendency to agglomerate. CONCLUSIONS: TiF4
      containing adhesives did not influence uTBS or failure mode to dentin over time,
      although FS and DC were affected, especially when TiF4 was incorporated into the
      B. TiF4P presented excellent stability over time.

PMID- 28750303
TI  - Initial investigations of spectral measurements to estimate the time within
      stages of Protophormia terraenovae (Robineau-Desvoidy) (Diptera: Calliphoridae).
AB  - Current applications of forensic entomology to post-mortem interval estimations
      involve ageing the insects colonizing the remains based on minimum time to reach
      the oldest stage of development. Immature species of blow fly develop at a
      predictable rate to each stage of development in their lifecycle. Unfortunately,
      the minimum time to reach a stage of development can be a rather unrefined
      estimate of tenure on the body in the sometimes lengthy time frame of the later
      stages. In a successful attempt to narrow this time frame, daily spectral
      measurements of the immature stages of Protophormia terraenovae (Robineau
      Desvoidy) raised at a mean temperature of 24.6 degrees C were collected and the
      functional data analysis was completed. Functional regressions and coefficient
      functions were examined for model prediction and generalization. P. terraenovae
      is a Holarctic species as well as an early colonizer of human remains and is
      therefore, an excellent indicator species in North American death investigations.
      Spectral measurements can be used successfully to estimate the day of development
      in the third instar including post feeding stage. In the intra-puparial period,
      however, only the last day of development could be distinguished from the earlier
      days of the intra-puparial period. Distinguishing day within second instar is
      also possible for P. terraenovae raised at a mean temperature of 24.6 degrees C
      and, although not fully within the pointwise 95% confidence interval, it still
      accurately predicts the day. The results of this proof of concept research are
      promising and show a potential method for narrowing the original death estimates
      and offering a better overall estimate of age of P. terraenovae larvae and,
      therefore; estimated time since death.

PMID- 28750304
TI  - Stability of benzodiazepines in hair after prolonged exposure to chlorinated
      water.
AB  - INTRODUCTION: An in vitro study on authentic positive samples was carried out,
      aiming the evaluation of the effect of chlorinated water on benzodiazepines in
      hair. Two subjects exposed to chlorinated water for several consecutive times
      were also investigated. METHOD: Seven hair samples collected from autopsy cases,
      previously tested positive for benzodiazepines, were washed with dichloromethane
      and methanol. They were longitudinally divided in six aliquots of about 30mg. An
      aliquot was processed without treatment while other five ones were soaked in
      chlorinated water (0.1% sodium dichloroisocyanurate and 0,1M sulfuric acid at pH
      5.5) for 4, 20, 24 and 30h respectively. Hair samples were then processed
      following a fully validated and previously published method. Briefly hair samples
      were sonicated in 600 microliters methanol containing halazepam (IS) up to two
      hours. Ten microliters were injected in a liquid chromatographic tandem mass
      spectrometric (LC-MS/MS) system. Analytes were eluted from a C18 reversed-phased
      column. Two transitions on multiple reaction monitoring and positive ionization
      mode were monitored for each compound. RESULT AND DISCUSSIONS: Six compounds
      among benzodiazepines and metabolites were identified and quantified in the seven
      hair samples: diazepam (575pg/mg), desmethyldiazepam (562pg/mg),
      chlordesmethyldiazepam (173pg/mg), desalkylflurazepam (320pg/mg), clonazepam
      (three cases-195, 119 and 111pg/mg respectively), lormetazepam (two cases-182 and
      416pg/mg respectively). Traces of 7-aminoclonazepam were identified into 2
      samples. Stability of benzodiazepines in water was evaluated by soaking an
      aliquot of hair for up to 30h in deionized water. No significant degradation was
      observed. Samples soaked in chlorinated water showed considerable decreasing from
      the initial concentration even after the 4-h treatment: the fastest degradation
      was provided by clonazepam that showed a 61% loss. The greatest loss was measured
      for diazepam (86% loss after 30-h soaking). CONCLUSION: To the best of our
      knowledge this is the first in vitro study that evaluated benzodiazepines
      stability in hair after prolonged exposure to chlorinated water. The results
      showed that the longer the exposure the higher the degradation. Prolonged
      exposure to chlorinated water and sunlight must be always taken into account as
      possible causes of false negative results.

PMID- 28750305
TI  - Progressive hippocampal sclerosis after viral encephalitis: Potential role of
      NMDA receptor antibodies.
AB  - PURPOSE: Survivors of viral encephalitis can develop refractory epilepsy and
      hippocampal sclerosis. Both the initial infectious insult and the secondary
      effects of recurrent seizures have been implicated in chronic disease
      progression. Recently, post-infectious autoimmunity, involved in acute relapses,
      has also been proposed as a pathomechanism for chronic disease progression. Our
      case series suggests a potential role of antibodies against the N-methyl-d
      aspartate receptor (NMDAR) in chronic inflammatory disease beyond acute
      manifestations. METHODS: Retrospective chart review of four patients with
      epilepsy, hippocampal sclerosis following viral encephalitis and NMDAR-antibodies
      in CSF. RESULTS: The four patients were female, developed hippocampal sclerosis
      (in 3/4 in a step-wise progression) after Herpes simplex or Varicella zoster
      virus encephalitis and harboured immunoglobulin G antibodies against the NMDAR in
      their CSF. Two patients were treated with short-term immunosuppression but did
      not benefit. CONCLUSION: This case series presents the first tentative evidence
      in support of chronic autoimmune inflammation driving disease progression after
      viral encephalitis beyond the known acute immune-mediated relapses. The anecdotal
      nature of the data does not, however, permit conclusive judgement on causality.
      Should our findings be replicated in larger cohorts, the treatment of post
      infectious epilepsy could potentially be expanded to include immunosuppressive
      strategies in antibody-positive cases.

PMID- 28750306
TI  - Electrical characterization of C28 fullerene junctions formed with group 1B metal
      electrodes.
AB  - We present an atomistic theory of electronic transport through single molecular
      junctions based on smallest stable fullerene molecule, C28. The electronic
      properties of single molecular junctions critically depend on the nature of
      electrode material. The two probe device is modeled by constraining C28 between
      two semi-infinite metal electrodes, from group 1B of periodic table, copper,
      silver and gold. We have highlighted the correlated phenomena of resonant
      conduction and current driven dynamics in molecular junctions using extendend
      Huckel theory in combination with non equilibrium Green's function framework. We
      conclude strong dependence of conductance on transmissions, which leads to
      oscillating conductance spectrum. An interesting interplay between conducting
      channels and different degrees of spatial localization and delocalization of
      molecular orbitals is evinced. The physical origin of current and conductance of
      so-formed C28 molecular junctions is discussed in detail by analysing their
      density of states, transmission spectra, molecular orbital analysis,
      rectification ratio and molecular projected self consistent Hamiltonian eigen
      states at different operating voltages ranging from -2V to +2V.

PMID- 28750307
TI  - Resilient protein co-expression network in male orbitofrontal cortex layer 2/3
      during human aging.
AB  - The orbitofrontal cortex (OFC) is vulnerable to normal and pathologic aging.
      Currently, layer resolution large-scale proteomic studies describing "normal" age
      related alterations at OFC are not available. Here, we performed a large-scale
      exploratory high-throughput mass spectrometry-based protein analysis on OFC layer
      2/3 from 15 "young" (15-43 years) and 18 "old" (62-88 years) human male subjects.
      We detected 4193 proteins and identified 127 differentially expressed (DE)
      proteins (p-value <=0.05; effect size >20%), including 65 up- and 62
      downregulated proteins (e.g., GFAP, CALB1). Using a previously described
      categorization of biological aging based on somatic tissues, that is, peripheral
      "hallmarks of aging," and considering overlap in protein function, we show the
      highest representation of altered cell-cell communication (54%), deregulated
      nutrient sensing (39%), and loss of proteostasis (35%) in the set of OFC layer
      2/3 DE proteins. DE proteins also showed a significant association with several
      neurologic disorders; for example, Alzheimer's disease and schizophrenia.
      Notably, despite age-related changes in individual protein levels, protein co
      expression modules were remarkably conserved across age groups, suggesting robust
      functional homeostasis. Collectively, these results provide biological insight
      into aging and associated homeostatic mechanisms that maintain normal brain
      function with advancing age.

PMID- 28750308
TI  - An innovative validated spectrofluorimetric method for determination of
      Lisinopril in presence of hydrochlorothiazide; application to content uniformity
      testing.
AB  - A new sensitive and discriminating spectrofluorimetric method has been developed
      and validated for determination of Lisinopril, one of the angiotensin converting
      enzyme inhibitors, in its pure bulk form and pharmaceutical tablets. The reaction
      of Lisinopril with ethylacetoacetate and formaldehyde in acidic buffered medium
      (pH3.8) has yielded a pale yellow product that exhibited a high fluorescence
      measured at 438nm after excitation at 350nm. All the experimental parameters
      affecting the formation and stability of the produced fluorophore were carefully
      investigated and optimized to give the maximum sensitivity. The fluorescence
      intensity was directly proportional to the drug concentration in the range of 0.5
      4.5MUg/mL with a limit of detection equal to 0.16MUg/mL. The method was
      successfully applied in the analysis of the commercially available pharmaceutical
      tablets containing the single drug or its binary mixtures with
      Hydrochlorothiazide. Furthermore, the developed procedure was adapted for
      studying the content uniformity test of some dosage forms containing the cited
      drug.

PMID- 28750309
TI  - Ultraviolet resonance Raman spectroscopy for the detection of cocaine in oral
      fluid.
AB  - Detecting and quantifying cocaine in oral fluid is of significant importance for
      practical forensics. Up to date, mainly destructive methods or biochemical tests
      have been used, while spectroscopic methods were only applied to pretreated
      samples. In this work, the possibility of using resonance Raman spectroscopy to
      detect cocaine in oral fluid without pretreating samples was tested. It was found
      that ultraviolet resonance Raman spectroscopy with 239-nm excitation allows for
      the detection of cocaine in oral fluid at 10MUg/mL level. Further method
      development will be needed for reaching the practically useful levels of cocaine
      detection.

PMID- 28750310
TI  - Manual therapy, exercise therapy or combined treatment in the management of adult
      neck pain - A systematic review and meta-analysis.
AB  - BACKGROUND: Neck pain is a common and often disabling musculoskeletal condition.
      Two therapies frequently prescribed for its management are manual therapy (MT)
      and exercise therapy (ET), and combining these treatment approaches are common.
      OBJECTIVE: To assess whether or not combined treatment consisting of MT and ET is
      more effective than either therapy alone in relieving pain and improving function
      in adult patients with grade I-II neck pain. DESIGN: Systematic review with meta
      analysis. METHODS: A systematic search on EMBASE, MEDLINE, AMED, CENTRAL and
      PEDro were performed until June 2017. Randomized controlled trials with adult
      grade I-II neck pain patients were included if they investigated the combined
      effect of MT and ET to the same ET or MT alone, and reported pain intensity or
      disability on numerical scales. Quality of life was assessed as a secondary
      outcome. Quality of the included trials was assessed with the PEDro scale, and
      the quality of evidence was assessed with GRADE. RESULTS: 1169 articles were
      screened, and 7 studies were included, all of which investigated the addition of
      ET to MT. Only very small and non-significant between group differences was found
      on pain intensity at rest, neck disability, and quality of life at immediate post
      treatment, 6 months, and 12 months follow-up. The quality of evidence was
      moderate for pain-at-rest outcomes and moderate too low for neck disability and
      quality of life outcomes. CONCLUSION: Combined treatment consisting of MT and ET
      does not seem to be more effective in reducing neck pain intensity at rest, neck
      disability or improving quality of life in adult patients with grade I-II neck
      pain, than ET alone.

PMID- 28750312
TI  - Synthesis of 2-imino and 2-hydrazono thiazolo[4,5-d]pyrimidines as corticotropin
      releasing factor (CRF) antagonists.
AB  - Corticotropin-releasing factor (CRF) is an important neuropeptide hormone which
      controls the body's overall response to stress. It plays a crucial role in
      regulating the behavioral, cardiovascular, immune and gastrointestinal systems.
      Over-activation of the CRF system has been implicated in many disorders including
      anxiety, depression, drug addiction, hypertension, Irritable Bowel Syndrome
      (IBS), peptic ulcers, inflammation and others. Thus, binding of CRF to its
      receptors is an attractive target to develop new medications which aim at
      treating ailments associated with chronic stress. Numerous small-molecule non
      peptide CRF receptor antagonists were developed and many are in various stages in
      clinical trials. Many showed great promise in treatment of anxiety, depression,
      peptic ulcers, inflammation, IBS and drug addiction. In our recent previous work,
      the development of two series of pyrimidine and fused pyrimidine CRF antagonists
      were described. In continuation of our efforts in this direction, in the current
      manuscript, the synthesis of a third series of CRF receptor antagonists is
      described. The binding affinities of select compounds for the type 1 receptor of
      CRF (CRF1R) were determined and compared to a standard CRF antagonist drug
      antalarmin. A lead compound was identified and further evaluated by measuring its
      effect on the inhibition of the agonist-stimulated accumulation of second
      messengers.

PMID- 28750311
TI  - Synthesis and antiangiogenic activity study of new hop chalcone Xanthohumol
      analogues.
AB  - Angiogenesis induction is a hallmark of cancer. Antiangiogenic properties of
      Xanthohumol (XN), a naturally occurring prenylated chalcone from hops, have been
      widely reported. Here we describe the synthesis and study the antiangiogenic
      activity in vitro of a series of XN derivatives, where different substituents on
      the B-ring of the chalcone scaffold were inserted. The new XN derivatives
      inhibited human umbilical-vein endothelial cell (HUVEC) proliferation, adhesion,
      migration, invasion and their ability to form capillary-like structures in vitro
      at 10 MUM concentration. The preliminary results indicate that the phenolic OH
      group in R, present in natural XN, is not necessary for having antiangiogenic
      activity. In fact, the most effective compound from this series, 13, was
      characterized by a para-methoxy group in R and a fluorine atom in R2 on B-ring.
      This study paves the way for future development of synthetic analogues of XN to
      be used as cancer angiopreventive and chemopreventive agents.

PMID- 28750313
TI  - Imidazo[1,2-a]pyrazine, Imidazo[1,5-a]quinoxaline and Pyrazolo[1,5-a]quinoxaline
      derivatives as IKK1 and IKK2 inhibitors.
AB  - The transcription nuclear factor NF-kappaB plays a pivotal role in chronic and
      acute inflammatory diseases. Among the several and diverse strategies for
      inhibiting NF-kappaB, one of the most effective approach considered by the
      pharmaceutical industry seems to be offered by the development of IKK inhibitors.
      In a former study, two potential IKK2 inhibitors have been highlighted among a
      series of imidazo[1,2-a]quinoxaline derivatives. In order to enhance this
      activity, we present herein the synthesis of twenty-one new compounds based on
      the imidazo[1,2-a]pyrazine, imidazo[1,5-a]quinoxaline or pyrazolo[1,5
      a]quinoxaline structures. Their potential to inhibit IKK1 and IKK2 activities is
      also tested.

PMID- 28750314
TI  - Endoscopic clipping of spontaneous esophageal rupture: Case reports of three
      patients.
AB  - INTRODUCTION: Spontaneous esophageal rupture is a life-threatening condition
      which is difficult to diagnose early, and is usually treated surgically.
      Prolonged hospitalization is common. Non-operative treatment of esophageal
      rupture localized to the mediastinum has been reported. We report three patients
      with spontaneous esophageal rupture successfully managed with endoscopic
      clipping. CASE PRESENTATIONS: Two patients had ruptures localized to the
      mediastinum, and were discharged within one week of undergoing closure. The third
      patient presented with Boerhaave's syndrome with a leak into the pleural space
      and needed prolonged hospitalization (34days), but she did not need surgery and
      began oral intake two days after endoscopic clipping. The patient had an
      uneventful recovery.

PMID- 28750315
TI  - A chip off the old block-A case report of gallstone ileus in which identification
      of a facetted stone was essential in preventing re-laparotomy.
AB  - Gallstone ileus is a rare presentation, accounting for 0.1% of cases of
      mechanical small bowel obstruction. Patients are often elderly with significant
      comorbidity. Treatment is based upon laparotomy and enterolithotomy. We present
      the case of a 75year old lady admitted as an emergency with a 4day history of
      small bowel obstruction. She was found on CT scan to have an impacted gallstone
      in the distal ileum. At operation, her impacted stone was removed through a
      proximal enterostomy. The stone however was found to have a squared off edge,
      raising the suspicion of a second fragment within the proximal small bowel lumen.
      Failure to retrieve this could have led to re-obstruction requiring a return to
      theatre and repeat laparotomy in an elderly patient with the associated
      morbidity.

PMID- 28750316
TI  - Diffuse field full matrix capture for near surface ultrasonic imaging.
AB  - This article reports a technique for near-surface ultrasonic array imaging.
      Information equivalent to an undelayed full matrix of inter-element responses is
      produced through cross-correlation of a later time diffuse full matrix. This
      reconstructed full matrix lacks the nonlinear effects of early time saturation
      present in a directly acquired response. Consequently the near-surface material
      information usually obscured by this effect is retrieved. Furthermore it is shown
      that a hybrid full matrix formed through a temporally weighted sum of coherent
      and reconstructed matrices allows for effective near-surface and bulk material
      imaging from a single direct-contact experimental realisation.

PMID- 28750317
TI  - Advantages of cooled fiber for monitoring laser tissue ablation through temporal
      and spectral analysis of RF ultrasound signal: A case study.
AB  - The promising minimally invasive laser thermal therapy technique may be improved
      if thermal lesions induced into the tissue can be carefully monitored in
      extension and morphology during the treatment. According to results obtained in
      several recent experimentations, solutions that avoid tissue carbonization during
      the treatment have been proposed, in order to allow deeper and longer lasting
      light penetration in treated tissue and to reduce failures of the applicator tip
      and fiber optic, dangerous for patients. In the work the advantages in using a
      cooled fiber are shown, in order not only to induce efficient lesions but also in
      performing an accurate monitoring by ultrasound. Indeed, one important limit of
      the ultrasound control is caused by the gas bubbles generation, which represent
      an acoustic barrier that invalidate the ultrasonic image representation of the
      treated tissue. Ultrasonic radiofrequency signals were acquired from the same
      bovine liver ex vivo sample by using both bare and cooled fiber and processed to
      produce B-mode and spectral parametric images by implementing TUV (Thermotherapy
      Ultrasonic View) algorithm. Radiofrequency signals, B-mode and TUV images were
      analysed and compared in order to evaluate the different tissue heating processes
      during ablation and the different lesion extensions induced into the tissue after
      the treatment. Cooled fiber avoided carbonization and strongly reduced gas
      bubbles generation inducing a larger lesion and allowing a more effective
      ultrasound monitoring. Moreover by correlating optical images of the lesions and
      the corresponding Integral TUV images, by using Dice and Jaccard coefficients, it
      was proven that TUV algorithm is able to characterize the tissue portions
      differently modified by ablation exhibiting better performances in the case of
      cooled fiber and revealing to be a potential tool capable to improve the laser
      delivery settings control.

PMID- 28750319
TI  - Theoretically obtained insight into the mechanism and dioxetanone species
      responsible for the singlet chemiexcitation of Coelenterazine.
AB  - Coelenterazine is a widespread bioluminescent substrate for a diverse set of
      marine species. Moreover, its imidazopyrazinone core is present in eight phyla of
      bioluminescent organisms. Given their very attractive intrinsic properties, these
      bioluminescent systems have been used in bioimaging, photodynamic therapy of
      cancer, as gene reporter and in sensing applications, among others. While it is
      known that bioluminescence results from the thermolysis of high-energy
      dioxetanones, the mechanism and dioxetanone species responsible for the singlet
      chemiexcitation of Coelenterazine are not fully understood. The theoretical
      characterization of the reactions of model Coelenterazine dioxetanones showed
      that efficient chemiexcitation is caused by a neutral dioxetanone with limited
      electron and charge transfer, by accessing a region of the PES where ground and
      excited states are nearly-degenerated. This finding was supported by calculation
      of equilibrium constants, which showed that only neutral dioxetanone is present
      in conditions associated with bioluminescence. Moreover, while cationic amino
      acids easily protonate amide dioxetanone, anionic ones cannot deprotonate the
      neutral species. These results indicate that, contrary to existent theories,
      efficient chemiexcitation can occur with significant electron and/or charge
      transfer. In fact, these processes can be prejudicial to chemiexcitation, as
      anionic dioxetanones showed a less efficient chemiexcitation despite the
      occurrence of significant electron and charge transfer.

PMID- 28750318
TI  - PEGylated (NH4)xWO3 nanorods as efficient and stable multifunctional nanoagents
      for simultaneous CT imaging and photothermal therapy of tumor.
AB  - The simultaneous imaging and photothermal therapy of tumors have attracted much
      attention, and a prerequisite is to obtain multifunctional nanomaterials.
      Ideally, one kind of nanoparticles with single component can be used as both
      imaging agent and photothermal agent. Herein, we have developed the PEGylated
      (NH4)xWO3 (denoted as (NH4)xWO3-PEG) nanorods as multifunctional nanoparticles
      with single semiconductor component. (NH4)xWO3-PEG nanorods with about 30nm
      diameter and length of several hundred nanometers have been obtained through a
      solvothermal synthesis-PEGylation two-step route. Under the irradiation of 980-nm
      laser with intensity of 0.72Wcm-2, aqueous dispersion of (NH4)xWO3-PEG nanorods
      (0.67-5.44mmol/L) displays high elevation (17.6-34.5 degrees C) of temperature in
      400s, accompanied by an excellent long-term photothermal stability. Furthermore,
      (NH4)xWO3-PEG nanorods exhibit as high as 6 times X-ray attenuation ability
      compared to that of the clinically used iodine-based X-ray computed tomography
      (CT) contrast agent (Iopromide). More importantly, after PBS solution of
      (NH4)xWO3-PEG nanorods is injected into the tumor of mice, the tumor can be
      effectively detected by CT imaging. Moreover, cancer cells in vivo can be further
      destroyed by the photothermal effects of (NH4)xWO3-PEG nanorods, under the
      irradiation of 980-nm laser with the safe intensity of 0.72Wcm-2 for 10min.
      Therefore, (NH4)xWO3-PEG nanorods can be used as a new kind of stable and
      efficient multifunctional nanoagent with single component for simultaneous CT
      imaging and photothermal therapy of tumor.

PMID- 28750320
TI  - Cellular Mycosporine-like amino acids protect photosystem II of the
      Dinoflagellate Scrippsiella sweeneyae from ultraviolet radiation damage.
AB  - Photo-damage to photosystem II (PSII) from ultraviolet radiation (UVR) was
      determined using chlorophyll fluorescence in relation to sunscreen factors on the
      dinoflagellate Scrippsiella sweeneyae based on the cellular mycosporine-like
      amino acid contents (CMAAs, cell) and cell diameter (=light path, d). Three
      different CMAAs, cell were prepared by acclimating cells to three levels (30.8,
      15.2, and 7.7Wm-2) of photosynthetically active radiation (PAR). PAR-acclimated
      cells were exposed to PAR (0.64Wm-2)+UVR (3.94W m-2=2.51Wm-2 UVB+1.43Wm-2 UVA)
      for 12min. High PAR (HL) and medium PAR (NDF1) treatments acclimated cells to
      induce shinorine and porphyra-334 (longer lambdamax at 333 and 334nm); whereas,
      the low PAR (NDF2) treatment acclimated cells to induce mycosporine-glycine and
      palythine (shorter lambdamax at 310 and 320nm). Absorption spectra for the
      individual MAAs were reconstructed using the lambdamax and CMAAs, cell and were
      summed to reconstruct the absorption of the total CMAAs, cell (m2cell-1) to
      estimate the sunscreen factor (S[lambda]) at lambdamax. The highest S(lambdamax)
      was obtained for cells that acclimated to the highest PAR (highest CMAAs, cell
      and longest d); whereas, the lowest S(lambdamax) was obtained for cells
      acclimated to the lowest PAR (the lowest CMAAs, cell and the shortest d). CMAAs,
      cell contributed approximately 94%, whereas d contributed <6%, of the sunscreen
      factor (Slambdamax). UVR-induced damage was indexed with a temporal decrease in
      the optimum quantum yield (Fv/Fm) in the Photosystem II. The highest damage was
      observed for cells acclimated to the lowest Slambdamax (lowest CMAAs, cell and
      shortest d); whereas, the lowest damage was observed for cells acclimated to the
      highest Slambdamax (highest CMAAs, cell and longest d). The CMAAs, cell mitigated
      most of the UVR-induced damage in photosystem II of the dinoflagellate S.
      sweeneyae.

PMID- 28750321
TI  - Modeling the evolution of SIV sooty mangabey progenitor virus towards HIV-2 using
      humanized mice.
AB  - HIV-2 is thought to have originated from an SIV progenitor native to sooty
      mangabeys. To model the initial human transmission and understand the sequential
      viral evolution, humanized mice were infected with SIVsm and serially passaged
      for five generations. Productive infection was seen by week 3 during the initial
      challenge followed by chronic viremia and gradual CD4+ T cell decline. Viral
      loads increased by the 5th generation resulting in more rapid CD4+ T cell
      decline. Genetic analysis revealed several amino acid substitutions that were
      nonsynonymous and fixed in multiple hu-mice across each of the 5 generations in
      the nef, env and rev regions. The highest rate of substitution occurred in the
      nef and env regions and most were observed within the first two generations.
      These data demonstrated the utility of hu-mice in modeling the SIVsm transmission
      to the human and to evaluate its potential sequential evolution into a human
      pathogen of HIV-2 lineage.

PMID- 28750322
TI  - Longitudinal sequencing of HIV-1 infected patients with low-level viremia for
      years while on ART shows no indications for genetic evolution of the virus.
AB  - HIV-infected patients on antiretroviral therapy (ART) may present low-level
      viremia (LLV) above the detection level of current viral load assays. In many
      cases LLV is persistent but does not result in overt treatment failure or
      selection of drug resistant viral variants. To elucidate whether LLV reflects
      active virus replication, we extensively sequenced pol and env genes of the viral
      populations present before and during LLV in 18 patients and searched for
      indications of genetic evolution. Maximum likelihood phylogenetic trees were
      inspected for temporal structure both visually and by linear regression analysis
      of root-to-tip and pairwise distances. Viral coreceptor tropism was assessed at
      different time points before and during LLV. In none of the patients consistent
      indications for genetic evolution were found over a median period of 4.8 years of
      LLV. As such these findings could not provide evidence that active virus
      replication is the main driver of LLV.

PMID- 28750323
TI  - Differential use of 3'CITEs by the subgenomic RNA of Pea enation mosaic virus 2.
AB  - The genomic RNA (gRNA) of Pea enation mosaic virus 2 (PEMV2) is the template for
      p33 and -1 frameshift product p94. The PEMV2 subgenomic RNA (sgRNA) encodes two
      overlapping ORFs, p26 and p27, which are required for movement and stability of
      the gRNA. Efficient translation of p33 requires two of three 3' proximal cap
      independent translation enhancers (3'CITEs): the kl-TSS, which binds ribosomes
      and engages in a long-distance interaction with the 5'end; and the adjacent eIF4E
      binding PTE. Unlike the gRNA, all three 3'CITEs were required for efficient
      translation of the sgRNA, which included the ribosome-binding 3'TSS. A hairpin in
      the 5' proximal coding region of p26/p27 supported translation by the 3'CITEs by
      engaging in a long-distance RNA:RNA interaction with the kl-TSS. These results
      strongly suggest that the 5' ends of PEMV2 gRNA and sgRNA connect with the 3'UTR
      through similar long-distance interactions while having different requirements
      for 3'CITEs.

PMID- 28750324
TI  - Infected T98G glioblastoma cells support human cytomegalovirus reactivation from
      latency.
AB  - T98G cells have been shown to support long-term human cytomegalovirus (HCMV)
      genome maintenance without infectious virus release. However, it remains unclear
      whether these viral genomes could be reactivated. To address this question, a
      recombinant HCMV (rHCMV) containing a GFP gene was used to infect T98G cells, and
      the infected cells absent of infectious virus production were designated T98G
      LrV. Upon dibutyryl cAMP plus IBMX (cAMP/IBMX) treatment, a serial of phenomena
      were observed, including GFP signal increase, viral genome replication, lytic
      genes expression and infectious viruses release, indicating the reactivation of
      HCMV in T98G-LrV cells from a latent status. Mechanistically, HCMV reactivation
      in the T98G-LrV cells induced by cAMP/IBMX was associated with the PKA-CREB
      signaling pathway. These results demonstrate that HCMV was latent in T98G-LrV
      cells and could be reactivated. The T98G-LrV cells represent an effective model
      for investigating the mechanisms of HCMV reactivation from latency in the context
      of neural cells.

PMID- 28750325
TI  - Cryo-EM maps reveal five-fold channel structures and their modification by
      gatekeeper mutations in the parvovirus minute virus of mice (MVM) capsid.
AB  - In minute virus of mice (MVM) capsids, icosahedral five-fold channels serve as
      portals mediating genome packaging, genome release, and the phased extrusion of
      viral peptides. Previous studies suggest that residues L172 and V40 are essential
      for channel function. The structures of MVMi wildtype, and mutant L172T and V40A
      virus-like particles (VLPs) were solved from cryo-EM data. Two constriction
      points, termed the mid-gate and inner-gate, were observed in the channels of
      wildtype particles, involving residues L172 and V40 respectively. While the mid
      gate of V40A VLPs appeared normal, in L172T adjacent channel walls were altered,
      and in both mutants there was major disruption of the inner-gate, demonstrating
      that direct L172:V40 bonding is essential for its structural integrity. In
      wildtype particles, residues from the N-termini of VP2 map into claw-like
      densities positioned below the channel opening, which become disordered in the
      mutants, implicating both L172 and V40 in the organization of VP2 N-termini.

PMID- 28750326
TI  - A putative hepatitis B virus splice variant associated with chronic hepatitis and
      liver cirrhosis.
AB  - Hepatitis B virus (HBV) pre-S deletion was associated with chronic hepatitis (CH)
      and liver cirrhosis (LC); however, the type of pre-S deletion associated with
      these conditions and the mechanism of the generation of pre-S deletion remain
      unknown. Here, pre-S sequences from asymptomatic carriers (ASCs) and carriers
      with CH or LC were analyzed. The results indicated that deletion in the S
      promoter and the C-terminal half of the pre-S1 region was more frequent in CH and
      LC patients than in ASCs. RNA splicing analysis revealed that one type of pre-S1
      deletion mutant, termed spPS1, was derived from splicing. This variant was
      associated with CH (12.7% vs. 1.8%, P = 0.06) and LC (14.5% vs. 1.8%, P = 0.032)
      when compared with ASC. In conclusion, spPS1, a putative splice variant; S
      promoter deletion mutant; and deletion in the C-terminal half of the pre-S1
      region were closely associated with CH and LC development.

PMID- 28750327
TI  - Cholesterol is required for stability and infectivity of influenza A and
      respiratory syncytial viruses.
AB  - Cholesterol-rich lipid raft microdomains in the plasma membrane are considered to
      play a major role in the enveloped virus lifecycle. However, the functional role
      of cholesterol in assembly, infectivity and stability of respiratory RNA viruses
      is not fully understood. We previously reported that depletion of cellular
      cholesterol by cholesterol-reducing agents decreased production of human
      parainfluenza virus type 1 (hPIV1) particles by inhibiting virus assembly. In
      this study, we analyzed the role of cholesterol on influenza A virus (IAV) and
      respiratory syncytial virus (RSV) production. Unlike hPIV1, treatment of human
      airway cells with the agents did not decrease virus particle production. However,
      the released virions were less homogeneous in density and unstable. Addition of
      exogenous cholesterol to the released virions restored virus stability and
      infectivity. Collectively, these data indicate a critical role of cholesterol in
      maintaining IAV and RSV membrane structure that is essential for sustaining viral
      stability and infectivity.

PMID- 28750328
TI  - Inactivation efficiency of plasmid-encoded antibiotic resistance genes during
      water treatment with chlorine, UV, and UV/H2O2.
AB  - This study assessed the inactivation efficiency of plasmid-encoded antibiotic
      resistance genes (ARGs) both in extracellular form (e-ARG) and present within
      Escherichia coli (intracellular form, i-ARG) during water treatment with
      chlorine, UV (254 nm), and UV/H2O2. A quantitative real-time PCR (qPCR) method
      was used to quantify the ARG damage to ampR (850 bp) and kanR (806 bp) amplicons,
      both of which are located in the pUC4K plasmid. The plate count and flow
      cytometry methods were also used to determine the bacterial inactivation
      parameters, such as culturability and membrane damage, respectively. In the first
      part of the study, the kinetics of E. coli inactivation and ARG damage were
      determined in phosphate buffered solutions. The ARG damage occurred much more
      slowly than E. coli inactivation in all cases. To achieve 4-log reduction of ARG
      concentration at pH 7, the required chlorine exposure and UV fluence were 33-72
      (mg * min)/L for chlorine and 50-130 mJ/cm2 for UV and UV/H2O2. After increasing
      pH from 7 to 8, the rates of ARG damage decreased for chlorine, while they did
      not vary for UV and UV/H2O2. The i-ARGs mostly showed lower rates of damage
      compared to the e-ARGs due to the protective roles of cellular components against
      oxidants and UV. The contribution of OH radicals to i-ARG damage was negligible
      in UV/H2O2 due to significant OH radical scavenging by cellular components. In
      all cases, the ARG damage rates were similar for ampR versus kanR, except for the
      chlorination of e-ARGs, in which the damage to ampR occurred faster than that to
      kanR. Chlorine and UV dose-dependent ARG inactivation levels determined in a
      wastewater effluent matrix could be reasonably explained by the kinetic data
      obtained from the phosphate buffered solutions and the expected oxidant (chlorine
      and OH radicals) demands by water matrix components. These results can be useful
      in optimizing chlorine and UV-based disinfection systems to achieve ARG
      inactivation.

PMID- 28750329
TI  - Depth of the vadose zone controls aquifer biogeochemical conditions and extent of
      anthropogenic nitrogen removal.
AB  - We investigated biogeochemical conditions and watershed features controlling the
      extent of nitrate removal through microbial dinitrogen (N2) production within the
      surficial glacial aquifer located on the north and south shores of Long Island,
      NY, USA. The extent of N2 production differs within portions of the aquifer, with
      greatest N2 production observed at the south shore of Long Island where the
      vadose zone is thinnest, while limited N2 production occurred under the thick
      vadose zones on the north shore. In areas with a shallow water table and thin
      vadose zone, low oxygen concentrations and sufficient DOC concentrations are
      conducive to N2 production. Results support the hypothesis that in aquifers
      without a significant supply of sediment-bound reducing potential, vadose zone
      thickness exerts an important control of the extent of N2 production. Since
      quantification of excess N2 relies on knowledge of equilibrium N2 concentration
      at recharge, calculated based on temperature at recharge, we further identify
      several features, such as land use and cover, seasonality of recharge, and
      climate change that should be considered to refine estimation of recharge
      temperature, its deviation from mean annual air temperature, and resulting
      deviation from expected equilibrium gas concentrations.

PMID- 28750330
TI  - Modelling the transport and decay processes of microbial tracers in a macro-tidal
      estuary.
AB  - The Loughor Estuary is a macro-tidal coastal basin, located along the Bristol
      Channel, in the South West of the U.K. The maximum spring tidal range in the
      estuary is up to 7.5 m, near Burry Port Harbour. This estuarine region can
      experience severe coastal flooding during high spring tides, including extreme
      flooding of the intertidal saltmarshes at Llanrhidian, as well as the lower
      industrial and residential areas at Llanelli and Gowerton. The water quality of
      this estuarine basin needs to comply with the designated standards for safe
      recreational bathing and shellfish harvesting industries. The waterbody however,
      potentially receives overloading of bacterial inputs that enter the estuarine
      system from both point and diffuse sources. Therefore, a microbial tracer study
      was carried out to get a better understanding of the faecal bacteria sources and
      to enable a hydro-environmental model to be refined and calibrated for both
      advection and dispersion transport. A two-dimensional hydro-environmental model
      has been refined and extended to predict the highest water level covering the
      intertidal floodplains of the Loughor Estuary. The validated hydrodynamic model
      for both water levels and currents, was included with the injected mass of
      microbial tracer, i.e. MS2 coliphage from upstream of the estuary, and modelled
      as a non-conservative tracer over several tidal cycles through the system. The
      calibration and validation of the transport and decay of microbial tracer was
      undertaken, by comparing the model results and the measured data at two different
      sampling locations. The refined model developed as a part of this study, was used
      to acquire a better understanding of the water quality processes and the
      potential sources of bacterial pollution in the estuary.

PMID- 28750331
TI  - The study of protein biomarkers to understand the biochemical processes
      underlying beef color development in young bulls.
AB  - This study investigates relationships between 21 biomarkers and meat color traits
      of Longissimus thoracis muscles of young Aberdeen Angus and Limousin bulls. The
      relationships found allowed to propose metabolic processes underlying meat color.
      The color coordinates were related with several biomarkers. The relationships
      were in some cases breed-dependent and the variability explained in the
      regression models varied between 31 and 56%. The correlations between biomarkers
      and color parameters were sometimes opposite between breeds. The PCA using the 21
      biomarkers and the instrumental color coordinates showed that these variables
      discriminated efficiently between the two studied breeds. Results are coherent
      with earlier studies on other beef breeds showing that several proteins belonging
      to different but partly related biological pathways involved in muscle
      contraction, metabolism, heat stress and apoptosis are related to beef color. The
      results suggest that in future, biomarkers may be used to classify meat cuts
      sampled early post-mortem according to their forthcoming color.

PMID- 28750332
TI  - The effect of temperature in the range of -0.8 to 4 degrees C on lamb meat color
      stability.
AB  - This study investigated effects of controlled freezing point storage (CFPS, -0.8
      degrees C) on lamb color stability compared with storage at 4 degrees C
      (control). The muscle samples (n=5) of longissimus thoracis et lumborum from both
      carcass sides were assigned randomly to the two storage treatments and stored for
      10days. The a*, b*, R630/580 and Chroma values of samples stored in CFPS were
      significantly higher than that of samples in control from day 2 to day 10
      (P<0.05). Higher relative content of oxymyoglobin but lower relative content of
      metmyoglobin were observed in samples stored in CFPS treatment than those in
      control over 10days of storage (P<0.05). Meat samples stored in CFPS group had a
      significantly higher NADH content and metmyoglobin reductase activity than that
      in control group. In conclusion, ovine muscle stored in CFPS treatment for 10days
      demonstrated better color stability in comparison with those in 4 degrees C
      storage.

PMID- 28750333
TI  - Mexican consumers at the point of meat purchase. Beef choice.
AB  - Within-consumer preference replication achieved through systematic image
      manipulation was used in consumer surveys in four cities across Mexico (Mexico
      City, n=195; Guadalajara, n=100; Hermosillo, n=132; Veracruz, n=61) to study beef
      preferences. Images of beef steaks controlled for lean and fat colour, fat cover
      and marbling were presented to consumers to determine the characteristics used in
      beef choice and the levels of preference of these characteristics. The most
      important choice criteria were fat cover (62% preferring little fat cover) and
      marbling (59% preferring non-marbled). Lean colour was also important with 24%
      and 29% choosing light and dark red beef, respectively. Fat colour was the least
      important of the four attributes studied (18% and 19% choosing white and yellow,
      respectively), but was nevertheless important given that 43% of consumers used
      three or four characteristics to make their choice. Imported and domestic beef in
      the Mexican marketplace appear to respond to the range of consumers' beef
      preferences at the point of purchase.

PMID- 28750334
TI  - Effects of sage distillation by-product (Salvia lavandulifolia Vahl.) dietary
      supplementation in light lambs fed on concentrates on meat shelf life and fatty
      acid composition.
AB  - Sage distillation by-product (SDB) was tested as dietary supplement in lambs for
      its effects on the lipid profile and meat stability. Segureno lambs from two
      different rearing systems (ewes grazing Mediterranean shrubland vs. ewes fed
      indoors on barley/lucerne) were weaned at 13kg live weight and given a basal diet
      (concentrate) or the SDB diet (concentrate with 100gSDBkg-1 feed) until they
      reached 25kg. Intramuscular fat composition and meat stability were determined.
      SDB increased n-3 PUFA and polyphenol intake. It was necessary to provide an n-3
      PUFA-promoting diet to both ewes (by grazing) and lambs (SDB) to increase the
      proportions of total PUFAs, n-3 PUFAs and CLA in meat. SDB had no antioxidant or
      antimicrobial effects; on the contrary, lipid oxidation, rancidity and lean
      discoloration were higher in retailed meat with high PUFA levels. Thus, the SDB
      based diet used needs to be readjusted to ensure that meat quality is improved
      irrespective of the diet provided to ewes.

PMID- 28750335
TI  - ironPhone: Mobile device-coupled point-of-care diagnostics for assessment of iron
      status by quantification of serum ferritin.
AB  - Iron deficiency (ID) is an urgent public health problem that has devastating
      effects on maternal and child health. However, due to poor access and
      affordability, screening and diagnosis for ID is often limited to proxy
      hemoglobin measurements alone. Here, we report the development and validation of
      ironPhone, a mobile-device coupled portable diagnostics for quantification of
      serum ferritin concentrations, an iron status biomarker, within a few minutes,
      from a drop of fingerprick blood. The ironPhone diagnostic platform comprises of
      a smartphone accessory, an app, and a disposable lateral flow immunoassay test
      strip to quantify serum ferritin. For initial validation in the lab, we optimized
      and evaluated the performance of ironPhone with known ferritin concentrations in
      spiked buffer and serum samples. Following lab validation, we performed a human
      validation by collecting fingerprick whole blood samples from 20 participants to
      assess iron status using ironPhone and compared the results with the laboratory
      standard IMMULITE 2000 analyzer. Findings from the ironPhone for the buffer and
      spiked serum samples provided a calibration curve with R2 values of 0.97 (n=27)
      and 0.93 (n=12), respectively. On comparison with the laboratory standard
      IMMULITE analyzer in whole blood samples, a correlation of 0.92 (P<0.0001) was
      observed with a sensitivity of over 90% for predicting ID (ferritin<15.0ug/L) via
      the ironPhone, demonstrating its promise for iron status assessment at the point
      of-care.

PMID- 28750336
TI  - Recent advances in biosensor technology in assessment of early diabetes
      biomarkers.
AB  - Discovery of biosensors has acquired utmost importance in the field of
      healthcare. Recent advances in biological techniques and instrumentation
      involving nanomaterials, surface plasmon resonance, and aptasensors have
      developed innovative biosensors over classical methods. Integrated approaches
      provided a better perspective for developing specific and sensitive devices with
      wide potential applications. Type 2 diabetes mellitus is a complex disease
      affecting almost every tissue and organ system, with metabolic complications
      extending far beyond impaired glucose metabolism. Although there is no known cure
      for Type 2 diabetes, early diagnosis and interventions are critical to prevent
      this disease and can postpone or even prevent the serious complications that are
      associated with diabetes. Biomarkers for type 2 diabetes are useful for
      prediction and intervention of the disease at earlier stages. Proper selection of
      biomarkers that represent health and disease states is vital for disease
      diagnosis and treatment by detecting it before it manifests. In this respect, we
      provide an overview of different types of biosensors being used, ranging from
      electrochemical, fluorescence-based, nanomonitors, SPR-based, and field-effect
      transistor biosensors for early detection and management of diabetes with focus
      on prediabetes. In the future, novel non-invasive technologies combined with
      blood and tissue-based biomarkers will enable the detection, prevention, and
      treatment of diabetes and its complications long before overt disease develops.

PMID- 28750337
TI  - Self-cleaned electrochemical protein imprinting biosensor basing on a thermo
      responsive memory hydrogel.
AB  - Herein, the self-cleaned electrochemical protein imprinting biosensor basing on a
      thermo-responsive memory hydrogel was constructed on a glassy carbon electrode
      (GCE) with a free radical polymerization method. Combining the advantages of
      thermo-responsive molecular imprinted polymers and electrochemistry, the resulted
      biosensor presents a novel self-cleaned ability for bovine serum albumin (BSA) in
      aqueous media. As a temperature controlled gate, the hydrogel film undergoes the
      adsorption and desorption of BSA basing on a reversible structure change with the
      external temperature stimuli. In particular, these processes have been revealed
      by the response of cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS) of electroactive [Fe(CN)6]3-/4-. The results have been
      supported by the evidences of scanning electron microscopy (SEM) and contact
      angles measurements. Under the optimal conditions, a wide detection range from
      0.02MUmolL-1 to 10MUmolL-1 with a detection limit of 0.012 MUmolL-1 (S/N = 3) was
      obtained for BSA. This proposed BSA sensor also possesses high selectivity,
      excellent stability, acceptable recovery and good reproducibility in its
      practical applications.

PMID- 28750338
TI  - MoS2-LA-PEI nanocomposite carrier for real-time imaging of ATP metabolism in
      glioma stem cells co-cultured with endothelial cells on a microfluidic system.
AB  - Stimuli-responsive carriers have extensively attracted attention in recent years.
      However, long-term and real-time tracking ability with stimuli-responsive carrier
      is still in its infant stage due to the limitations such as, low efficacy,
      instability and cytotoxicity in a bio-environment. In this work, we developed a
      reduction-sensitive carrier composed of lipoic acid-modified low molecular weight
      polyethyleneimine (LA-PEI) and large surface ratio MoS2 nanosheet integrated via
      disulfide bond to mimic a high molecular weight PEI. The positively charged
      carriers loading negatively charged aptamer enter the cells for a real time long
      term tracking of adenosine triphosphate (ATP) metabolism in glioma stem cells
      (GSCs) when stimulated by TGFbeta factor secreted from HUVECs. We envision that
      MoS2-LA-PEI carrier has a promising potential for delivery and monitoring the
      changes in live cells with low cytotoxicity and high efficiency.

PMID- 28750339
TI  - Differential neuronal and glial behavior on flat and micro patterned chitosan
      films.
AB  - Chitosan is a biodegradable natural polysaccharide that has been widely studied
      for regenerative purposes in the central nervous system. In this study we
      assessed the in vitro glial and neuronal cells response to chitosan either flat
      or patterned with grooves in the micrometric range. Chitosan demonstrated to be a
      good substrate for the attachment and growth of both neurons and glial cells.
      Chitosan micropatterns promoted glial cell maturation, suggesting astroglial
      activation. Nevertheless, those mature/reactive glial cells were permissive for
      axonal growth. Axons aligned and organized along the patterned grooves and the
      size of the linear topographic patterns is also affecting neurite and cell
      response. Patterns with 10MUm width induced fasciculation of axons, which can be
      useful for CNS tissue engineering substrates when precise orientation of the
      axonal outgrowth is desired.

PMID- 28750340
TI  - Activatable interpolymer complex-superparamagnetic iron oxide nanoparticles as
      magnetic resonance contrast agents sensitive to oxidative stress.
AB  - Magnetic resonance contrast agents that can be activated in response to specific
      triggers hold potential as molecular biosensors that may be of great utility in
      non-invasive disease diagnosis. We developed an activatable agent based on
      superparamagnetic iron oxide nanoparticles (SPIOs) that is sensitive to oxidative
      stress, a factor in the pathophysiology of numerous diseases. SPIOs were coated
      with poly(ethylene glycol) (PEG) and complexed with poly(gallol), a synthetic
      tannin. Hydrogen bonding between PEG and poly(gallol) creates a complexed layer
      around the SPIO that decreases the interaction of solute water with the SPIO,
      attenuating its magnetic resonance relaxivity. The complexed interpolymer
      nanoparticle is in an OFF state (decreased T2 contrast), where the contrast agent
      has a low T2 relaxivity of 7+/-2mM-1s-1. In the presence of superoxides, the
      poly(gallol) is oxidized and the polymers decomplex, allowing solute water to
      again interact with the SPIO, representing an ON state (increased T2 contrast)
      with a T2 relaxivity of 70+/-10mM-1s-1. These contrast agents show promise as
      effective sensors for diseases characterized in part by oxidative stress such as
      atherosclerosis, diabetes, and cancer.

PMID- 28750341
TI  - The enzyme-sensitive release of prodigiosin grafted beta-cyclodextrin and
      chitosan magnetic nanoparticles as an anticancer drug delivery system: Synthesis,
      characterization and cytotoxicity studies.
AB  - In present investigation, two glucose based smart tumor-targeted drug delivery
      systems coupled with enzyme-sensitive release strategy are introduced. Magnetic
      nanoparticles (Fe3O4) were grafted with carboxymethyl chitosan (CS) and beta
      cyclodextrin (beta-CD) as carriers. Prodigiosin (PG) was used as the model anti
      tumor drug, targeting aggressive tumor cells. The morphology, properties and
      composition and grafting process were characterized by transmission electron
      microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), vibration
      sample magnetometer (VSM), X-ray diffraction (XRD) analysis. The results revealed
      that the core crystal size of the nanoparticles synthesized were 14.2+/-2.1 and
      9.8+/-1.4nm for beta-CD and CS-MNPs respectively when measured using TEM; while
      dynamic light scattering (DLS) gave diameters of 121.1 and 38.2nm. The saturation
      magnetization (Ms) of bare magnetic nanoparticles is 50.10emucm-3, while
      modification with beta-CD and CS gave values of 37.48 and 65.01emucm-3,
      respectively. The anticancer compound, prodigiosin (PG) was loaded into the NPs
      with an encapsulation efficiency of approximately 81% for the beta-CD-MNPs, and
      92% for the CS-MNPs. This translates to a drug loading capacity of 56.17 and
      59.17mg/100mg MNPs, respectively. Measurement of in vitro release of prodigiosin
      from the loaded nanocarriers in the presence of the hydrolytic enzymes, alpha
      amylase and chitosanase showed that 58.1 and 44.6% of the drug was released after
      one-hour of incubation. Cytotoxicity studies of PG-loaded nanocarriers on two
      cancer cell lines, MCF-7 and HepG2, and on a non-cancerous control, NIH/3T3
      cells, revealed that the drug loaded nanoparticles had greater efficacy on the
      cancer cell lines. The selective index (SI) for free PG on MCF-7 and HepG2 cells
      was 1.54 and 4.42 respectively. This parameter was reduced for PG-loaded beta-CD
      MNPs to 1.27 and 1.85, while the SI for CS-MNPs improved considerably to 7.03 on
      MCF-7 cells. Complementary studies by fluorescence and confocal microscopy and
      flow cytometry confirm specific targeting of the nanocarriers to the cancer
      cells. The results suggest that CS-MNPs have higher potency and are better able
      to target the prodigiosin toxicity effect on cancerous cells than beta-CD-MNPs.

PMID- 28750342
TI  - The role of public and private natural space in children's social, emotional and
      behavioural development in Scotland: A longitudinal study.
AB  - INTRODUCTION: Poor mental health in childhood has implications for health and
      wellbeing in later life. Natural space may benefit children's social, emotional
      and behavioural development. We investigated whether neighbourhood natural space
      and private garden access were related to children's developmental change over
      time. We asked whether relationships differed between boys and girls, or by
      household educational status. METHODS: We analysed longitudinal data for 2909
      urban-dwelling children (aged 4 at 2008/9 baseline) from the Growing Up in
      Scotland (GUS) survey. The survey provided social, emotional and behavioural
      difficulty scores (Strengths and Difficulties Questionnaire (SDQ)), and private
      garden access. Area (%) of total natural space and parks within 500m of the
      child's home was quantified using Scotland's Greenspace Map. Interactions for
      park area, total natural space area, and private garden access with age and age2
      were modelled to quantify their independent contributions to SDQ score change
      over time. RESULTS: Private garden access was strongly related to most SDQ
      domains, while neighbourhood natural space was related to better social outcomes.
      We found little evidence that neighbourhood natural space or garden access
      influenced the trajectory of developmental change between 4 and 6 years,
      suggesting that any beneficial influences had occurred at younger ages.
      Stratified models showed the importance of parks for boys, and private gardens
      for the early development of children from low-education households. CONCLUSION:
      We conclude that neighbourhood natural space may reduce social, emotional and
      behavioural difficulties for 4-6 year olds, although private garden access may be
      most beneficial.

PMID- 28750343
TI  - Is ambient temperature associated with risk of infant mortality? A multi-city
      study in Korea.
AB  - BACKGROUND: Although numerous studies have shown increased risk of mortality from
      elevated temperatures for adults, limited studies have examined temperature's
      effect on mortality for infants. Our study investigated the city-specific and
      overall effects of ambient temperature on infant mortality in seven major cities
      in Korea, 2004-2007. METHODS: Birth cohort using a linked birth and death records
      included 777,570 births with 557 all-cause deaths. We estimated city-specific
      hazard ratios for each city using an extended Cox proportional hazards model with
      time-dependent covariates. Then we combined city-specific hazard ratios to
      generate overall hazard ratio across the seven cities using a Bayesian
      hierarchical model. Stratified analyses were conducted by cause of death (total
      and SIDS), exposure period (whole gestation, each trimester, lifetime, 1 month
      before death, and 2 weeks before death), sex, and maternal characteristics.
      RESULTS: Overall across the cities, we found significantly positive associations
      between ambient temperature during 1 month before death or 2 weeks before death
      and infant mortality from total or SIDS. The overall hazard ratio of infant
      mortality from total deaths and SIDS for a 1 degrees C increase during 1 month
      before death was 1.52 (95% CI, 1.46-1.57) and 1.50 (95% CI, 1.35-1.66),
      respectively. We also found suggestive evidence that some factors such as
      mother's age may modify the association. CONCLUSIONS: Our findings have
      implications for establishment of policy to reduce the risk of infant mortality
      from high ambient temperature under climate change.

PMID- 28750344
TI  - Aerosol pollution and its potential impacts on outdoor human thermal sensation:
      East Asian perspectives.
AB  - Aerosols affect the insolation at ground and thus the Aerosol Optical Depth (AOD,
      a measure of aerosol pollution) plays an important role on the variation of the
      Physiological Equivalent Temperature (PET) at locations with different aerosol
      climatology. The aerosol effects upon PET were studied for the first time at four
      East Asian cities by coupling a radiative transfer model and a human thermal
      comfort model which were previously well evaluated. Evident with the MODIS and
      AERONET AOD observations, the aerosol pollution at Beijing and Seoul was higher
      than at Chiayi (Taiwan) and Hong Kong. Based on the AERONET data, with background
      AOD levels the selected temperate cities had similar clear-sky PET values
      especially during summertime, due to their locations at similar latitudes. This
      also applied to the sub-tropical cities. Increase in the AOD level to the
      seasonal average one led to an increase in diffuse solar radiation and in turn an
      increase in PET for people living in all the cities. However, the heavy aerosol
      loading environment in Beijing and Seoul in summertime (AODs > 3.0 in episodic
      situations) reduced the total radiative flux and thus PET values in the cities.
      On the contrary, relatively lower episodic AOD levels in Chiayi and Hong Kong led
      to strong diffuse and still strong direct radiative fluxes and resulted in higher
      PET values, relative to those with seasonal averaged AOD levels. People tended to
      feel from "hot" to "very hot" during summertime when the AOD reached their
      average levels from the background level. This implies that in future aerosol
      effects add further burden to the thermal environment apart from the effects of
      greenhouse gas-induced global warming. Understanding the interaction between
      ambient aerosols and outdoor thermal environment is an important first step for
      effective mitigation measures such as urban greening to reduce the risk of human
      heat stress. It is also critical to make cities more attractive and enhancing to
      human well-being to achieve enhancing sustainable urbanization as one of the
      principal goals for the Nature-based Solutions.

PMID- 28750345
TI  - Are brief alcohol interventions targeting alcohol use efficacious in military and
      veteran populations? A meta-analysis.
AB  - BACKGROUND: Rates of hazardous and harm-related drinking are higher in the
      military and veteran populations compared to the general population. Brief
      alcohol interventions (BAIs) targeting alcohol use appear to reduce harmful
      drinking in the general population. However, less is known about the efficacy of
      BAIs targeting alcohol in military and veteran populations. METHODS: A systematic
      review and meta-analysis was conducted to assess the type and efficacy of BAIs
      used to reduce alcohol use in military and veteran populations conducted from
      2000 onwards. The meta-analysis was conducted using a standardised outcome
      measure of change in average weekly drinks (AWDs) from baseline to follow-up.
      RESULTS: The search revealed 10 papers that met the search criteria, and that
      reported data on 11 interventions included in the systematic review. 8 papers
      (reporting on 9 different interventions) were included in the meta-analysis after
      2 papers were excluded for which the relevant outcome data were not available.
      There was no overall effect of BAIs; a non-significant weekly drink reduction of
      0.95 drinks was found (95% CI, -0.17 to 2.07). This lack of efficacy persisted
      regardless of military group (conscripts, serving or veterans) and method of
      delivery (i.e., face-to-face, web-based or written information). Furthermore,
      sensitivity analyses revealed this small drink reduction was driven mainly by a
      single study. CONCLUSIONS: Based on these findings, existing BAIs do not seem to
      be efficacious in reducing alcohol use in military populations, despite some
      encouraging results from one electronic intervention which was of extensive
      duration.

PMID- 28750346
TI  - Relationship and community factors related to better mental health following
      child maltreatment among adolescents.
AB  - Research on factors associated with good mental health following child
      maltreatment is often based on unrepresentative samples and focuses on individual
      level factors. To address these gaps, the present study examined the association
      between relationship- and community-level factors and overall mental health
      status among adolescents with and without a history of maltreatment in a
      representative sample. Data were drawn from the National Comorbidity Survey of
      Adolescents (NCS-A; n=10,148; data collection 2001-2004); a large, cross
      sectional, nationally representative sample of adolescents aged 13-17 years from
      the United States. Having supportive parent and family relationships were
      significantly associated with good mental health (AOR ranging from 2.1 to 7.1).
      Positive community and school experiences were also significantly associated with
      good mental health (AOR ranging from 2.0 to 9.8). In most models, support from
      friends and siblings was not related to better mental health. Factors to be
      tested for efficacy in interventions targeted to adolescents with a history of
      child maltreatment include encouraging supportive parent and family
      relationships, and fostering positive community and school experiences.

PMID- 28750347
TI  - Global synchronization in finite time for fractional-order neural networks with
      discontinuous activations and time delays.
AB  - This paper is concerned with the global Mittag-Leffler synchronization and the
      synchronization in finite time for fractional-order neural networks (FNNs) with
      discontinuous activations and time delays. Firstly, the properties with respect
      to Mittag-Leffler convergence and convergence in finite time, which play a
      critical role in the investigation of the global synchronization of FNNs, are
      developed, respectively. Secondly, the novel state-feedback controller, which
      includes time delays and discontinuous factors, is designed to realize the
      synchronization goal. By applying the fractional differential inclusion theory,
      inequality analysis technique and the proposed convergence properties, the
      sufficient conditions to achieve the global Mittag-Leffler synchronization and
      the synchronization in finite time are addressed in terms of linear matrix
      inequalities (LMIs). In addition, the upper bound of the setting time of the
      global synchronization in finite time is explicitly evaluated. Finally, two
      examples are given to demonstrate the validity of the proposed design method and
      theoretical results.

PMID- 28750348
TI  - A comparative study on the activity of fungal lytic polysaccharide monooxygenases
      for the depolymerization of cellulose in soybean spent flakes.
AB  - Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes capable
      of the oxidative breakdown of polysaccharides. They are of industrial interest
      due to their ability to enhance the enzymatic depolymerization of recalcitrant
      substrates by glycoside hydrolases. In this paper, twenty-four lytic
      polysaccharide monooxygenases (LPMOs) expressed in Trichoderma reesei were
      evaluated for their ability to oxidize the complex polysaccharides in soybean
      spent flakes, an abundant and industrially relevant substrate. TrCel61A, a soy
      polysaccharide-active AA9 LPMO from T. reesei, was used as a benchmark in this
      evaluation. In total, seven LPMOs demonstrated activity on pretreated soy spent
      flakes, with the products from enzymatic treatments evaluated using mass
      spectrometry and high performance anion exchange chromatography. The hydrolytic
      boosting effect of the top-performing enzymes was evaluated in combination with
      endoglucanase and beta-glucosidase. Two enzymes (TrCel61A and Aspte6) showed the
      ability to release more than 36% of the pretreated soy spent flake glucose - a
      greater than 75% increase over the same treatment without LPMO addition.

PMID- 28750349
TI  - Escherichia coli maltose-binding protein (MBP) activates mouse Th1 through TLR2
      mediated MyD88-dependent pathway and TLR4-mediated TRIF-dependent pathway.
AB  - MBP (maltose-binding protein) is a component of Escherichia coli. Our previous
      study found that MBP directly induces the activation of Th1 (T helper type 1),
      but the molecular mechanism remains unclear. In the present study, CD4+T cells
      were purified from the spleens of normal mice using antibody-coated
      immunomagnetic beads by negative selection. CD4+T cells activated with a CD3/CD28
      antibody were stimulated with MBP. The results indicated that MBP elevated IFN
      gamma mRNA levels in activated CD4+T cells and promoted IFN-gamma production from
      activated CD4+T cells. To explore TLR2/TLR4 signaling involved in the mechanism
      of MBP-induced activation of Th1, we further detected downstream molecules of
      TLR2/TLR4 signaling. We found that MBP increased the mRNA levels of MyD88, TRAF6,
      TRIF and TRAF3 expressed in CD4+T cells. The results suggested that downstream
      molecules of TLR2/TLR4 signaling may be involved in MBP-induced activation of
      CD4+T cells. Furthermore, MyD88, TRIF, TRAF3 and TRAF6 expressed in activated
      CD4+T cells blocked with anti-TLR2 antibody or anti-TLR4 antibody followed by
      treatment with MBP were detected via RT-PCR and western blotting, respectively.
      MBP decreased the production of IFN-gamma in CD4+T cells in the presence of anti
      TLR2, accompanied by the down-regulated expression of MyD88 and TRAF6. However,
      MBP increased the production of IFN-gamma in CD4+T cells in the presence of anti
      TLR4 antibody accompanied by the up-regulated expression of MyD88 and the down
      regulated expression of TRIF, TRAF6 and TRAF3. The results suggested that the
      MyD88-dependent pathway of TLR2 and TRIF-dependent pathway are involved in the
      mechanism of Th1 activation induced by MBP. Our study has contributed to the
      clarification of the molecular mechanism of MBP-induced activation of CD4+T
      cells.

PMID- 28750350
TI  - Is macrophage polarization important in rheumatoid arthritis?
AB  - Macrophages are myeloid immune cells which are strategically positioned
      throughout the body, where they engulf and degrade debris, dead cells, and
      foreign substances, and coordinating the inflammatory processes. Macrophages can
      be divided into two extreme subsets, classical activation (M1), and alternatively
      activation (M2). The symptoms and signs of rheumatoid arthritis (RA) would
      exacerbate with the increase in pro-inflammatory cytokines, whereas anti
      inflammatory cytokines will alleviate the symptoms and signs of RA. This review,
      mainly discusses the effects of Notch, JNK and ERK signaling pathways on the
      regulation of macrophage polarization, and the effects of pro-inflammatory
      factors and/or anti-inflammatory cytokines produced by polarized macrophages in
      RA. Also, we will make an attempt to find out the importance of macrophage
      polarization in RA treatment as a drug target.

PMID- 28750351
TI  - Engineering resistance to virus transmission.
AB  - Engineering plants for resistance to virus transmission by invertebrate vectors
      has lagged behind other forms of plant protection. Vectors typically transmit
      more than one virus. Thus, vector resistance could provide a wider range of
      protection than defenses directed solely against one virus or virus group. We
      discuss current knowledge of vector-host-virus interactions, the roles of viral
      gene products in host and vector manipulation, and the effects of semiochemicals
      on host-vector interactions, and how this knowledge could be employed to disrupt
      transmission dynamics. We also discuss how resistance to vectors could be
      generated through genetic engineering or gene editing or indirectly through use
      of biocontrol using plant-resident viruses that infect vectors.

PMID- 28750352
TI  - Modelling the external radiation exposure from the Chernobyl fallout using data
      from the Swedish municipality measurement system.
AB  - In connection with the Chernobyl fallout and the subsequent deposition of
      radionuclides in Sweden, Swedish municipalities launched a measurement program to
      monitor the external radiation exposure. This program encompasses measurements of
      the ambient dose equivalent rate 1 m above ground at selected locations, and
      repeats those measurements at the same locations at 7-month intervals.
      Measurement data compiled from the seven locations with the highest deposition
      were combined with data from aerial surveys since May 1986 of ground deposition
      of 137Cs, high-resolution gamma spectrometry performed at four locations in May
      1986, and measurements from fixed continuous air gamma rate monitoring stations
      from 28 April to 15 May 1986. Based on these datasets, a model of the time
      pattern of the external dose rate in terms of ambient dose equivalent rate from
      the Chernobyl fallout was developed. The decrease in the ambient dose equivalent
      rate could, on average, be described by a four-component exponential decay
      function with effective half-times of 6.8 +/- 0.3 d, 104 +/- 26 d, 1.0 +/- 0.02 y
      and 5.5 +/- 0.09 y, respectively. The predominant contributions to the external
      dose rate in the first month were from short-lived fission products superseded by
      134Cs and then 137Cs. Integrated over 70 y and using extrapolation of the curve
      fits, our model predicts that 137Cs contributes about 60% and 134Cs contributes
      about 30% of the external effective dose at these seven locations. The projected
      time-integrated 70 y external effective dose to an unshielded person from all
      nuclides per unit total activity deposition of 137Cs is estimated to be 0.29 +/-
      0.0.08 mSv/(kBq m-2). These results are in agreement with those found in
      Chernobyl contaminated Russian forest areas, and emphasize the usefulness of
      maintaining a long-term and regular measurement program in contaminated areas.

PMID- 28750353
TI  - Old and dangerous: Prison and dementia.
AB  - Older prisoners are the fastest growing group of prisoners in many countries. The
      purpose of this study is to explore the phenomenon of detention of persons
      suffering from dementia. Medline searches were conducted for relevant articles,
      chapters and books published until August 2016. Search terms included dementia,
      elderly, prison and criminal. Publications found through this indexed search were
      reviewed for further relevant references. As results, there is a lack of data
      about elderly with dementia in prisons. Given the rise in the average age, it is
      reasonable to hypothesize that the number of older prisoners is growing.
      Moreover, some elderly are imprisoned with a concomitant cognitive impairment or
      psychiatric disorder while others will develop such diseases once incarcerated.
      At the present time, legal and social systems seem unprepared to handle the
      phenomenon of dementia in prison. As proposal, health assessments for older first
      time offenders should become a practice inside the correctional facilities and
      include an evaluation for specific health issues, such as psychiatric comorbidity
      and cognitive impairment.

PMID- 28750354
TI  - Assessing tumor extent on contrast-enhanced spectral mammography versus full
      field digital mammography and ultrasound.
AB  - OBJECTIVES: To compare breast cancer size measurements on full-field digital
      mammography (FFDM), contrast-enhanced spectral mammography (CEDM), and ultrasound
      (US), with histologic tumor size used as the reference standard. Material and
      methods The HIPAA complaint, IRB approved study comprised 88 women with newly
      diagnosed breast cancer who underwent FFDM and CEDM;74 also had US. Breast
      density, histologic subtype, and maximum tumor measurements were recorded.
      RESULTS: Pearson correlation coefficients for FFDM, US, and CEDM vs
      histopathology were 0.598, 0.639, and 0.859, respectively (P<0.001). The
      following correlation coefficients were calculated for dense breasts (n=48):
      histopathology vs FFDM (0.555), US (0.633), and CEDM (0.843) (P<0.001); for
      nondense breasts (n=40), they were FFDM (0.618), US (0.512), and CEDM (0.885)
      (P<0.001). For size difference, the mean (SD) for histopathology vs FFDM, US, and
      CEDM was -1.3 (11.9) mm, -2.8 (11.1) mm, and 2.9 (9.5) mm, respectively. Limits
      of agreement were -24.8 to 22.0mm, -24.5 to 18.8mm, and -15.6 to 21.4mm,
      respectively. CONCLUSIONS: In patients with biopsy-proven malignancy, size
      measurements correlated well with histopathologic size, and were higher on CEDM
      than those for FFDM and US in patients with dense or nondense breasts. The added
      value of CEDM as a supplement to FFDM in determining tumor size, however, was
      greater in patients with dense breasts. CEDM may be a promising alternative
      preoperative measurement tool for breast cancer patients with dense breasts
      and/or limited access or contraindications to MRI.

PMID- 28750355
TI  - Doxazosin nanoencapsulation improves its in vitro antiproliferative and
      anticlonogenic effects on breast cancer cells.
AB  - Doxazosin has been evaluated for the treatment of several types of cancer. Here,
      the antitumor effect of the nanoencapsulated form of doxazosin was evaluated in
      an in vitro model of breast cancer (MCF7 cell line). Doxazosin-loaded polymeric
      nanocapsules (DXZ-NC) were produced by interfacial deposition of preformed
      polymer with homogeneous aspect, spherical shape, mean diameter of about 130nm,
      positive zeta potential (+5mV), and encapsulation efficiency close to 35%. The
      Alamar Blue(r) assay and cell counting were carried out to assess cell viability
      and cell number, respectively. Mechanism of death was evaluated by
      Annexin/Propidium Iodide staining, while the long-term response was assessed
      using the clonogenic assay. Nuclear morphometric analysis was investigated using
      the NMA technique. A significant decrease in cell viability and clonogenicity was
      observed after the treatment with DXZ-NC when compared to the non-encapsulated
      drug. All treatments induced apoptosis as the main mechanism of toxicity. In
      conclusion, the nanoencapsulation of doxazosin improved its in vitro effects in
      MCF7 cells, without changing the mechanism of cell death underlying its toxicity.
      This approach was fundamental to reduce the long-term in vitro ability of the
      remaining tumor cells to form new colonies after the treatment, potentially
      reducing the risk of tumor recurrence.

PMID- 28750356
TI  - Combined calcitriol and menadione reduces experimental murine triple negative
      breast tumor.
AB  - BACKGROUND: Calcitriol (D) or 1,25(OH)2D3 inhibits the growth of several tumor
      cells including breast cancer cells, by activating cell death pathways. Menadione
      (MEN), a glutathione-depleting compound, may be used to potentiate the
      antiproliferative actions of D on cancer cells. We have previously shown in vitro
      that MEN improved D-induced growth arrest on breast cancer cell lines, inducing
      oxidative stress and DNA damage via ROS generation. Treatment with MEN+D resulted
      more effective than D or MEN alone. OBJECTIVE: To study the in vivo effect of
      calcitriol, MEN or their combination on the development of murine transplantable
      triple negative breast tumor M-406 in its syngeneic host. METHODS: Tumor M-406
      was inoculated s.c., and when tumors reached the desired size, animals were
      randomly assigned to one of four groups receiving daily i.p. injections of either
      sterile saline solution (controls, C), MEN, D, or both (MEN+D). Body weight and
      tumor volume were recorded three times a week. Serum calcium was determined
      before and at the end of the treatment, at which time tumor samples were obtained
      for histological examination. RESULTS: None of the drugs, alone or in
      combination, affected mice body weight in the period studied. The combined
      treatment reduced tumor growth rate (C vs. MEN+D, P<0.05) and the corresponding
      histological sections exhibited small remaining areas of viable tumor only in the
      periphery. A concomitant DNA fragmentation was observed in all treated groups and
      MEN potentiated the calcitriol effect on tumor growth. CONCLUSIONS: As previously
      observed in vitro, treatment with MEN and D delayed tumor growth in vivo more
      efficiently than the individual drugs, with evident signals of apoptosis
      induction. Our results propose an alternative protocol to treat triple negative
      breast cancer, using GSH depleting drugs together with calcitriol, which would
      allow lower doses of the steroid to maintain the antitumor effect while
      diminishing its adverse pharmacological effects.

PMID- 28750357
TI  - Protective effects of wedelolactone on dextran sodium sulfate induced murine
      colitis partly through inhibiting the NLRP3 inflammasome activation via AMPK
      signaling.
AB  - It has been reported that the ethanol extract of Wedelia chinensis attenuates
      murine colitis. Wedelolactone (WEL), a coumestane-type compound with many
      pharmacological activities, was isolated from W. chinensis. The present study
      aims to investigate the beneficial effects and underlying mechanisms of WEL on
      ulcerative colitis. In a dextran sodium sulfate (DSS)-induced mouse model, oral
      administration of WEL (50mg/kg) significantly attenuated pathological colonic
      damage and inhibited inflammatory infiltration, myeloperoxidase and alkaline
      phosphatase activities through MAPKs and NF-kappaB signaling pathways, while
      activating AMPK in colons treated with DSS. Further study revealed that WEL
      treatment dramatically inhibited NLRP3 inflammasome activation and caspase-1
      phosphorylation to decrease IL-1beta release in colons treated with DSS. In
      addition, WEL effectively regulates the disorder of skeleton proteins in colonic
      epithelial cells NCM460 exposed to TNF-alpha and protects the intestinal barrier
      function by activating AMPK in vivo. In summary, the AMPK-NLRP3-IL-1beta
      signaling axis plays an important role in colitis following WEL treatments. These
      findings provide new insights into the pharmacological actions of WEL as a
      potential therapeutic agent for colitis.

PMID- 28750358
TI  - Antitumor potential of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles in
      human bladder cancer cells.
AB  - Bladder cancer is a genitourinary malignant disease common worldwide. Current
      chemotherapy is often limited mainly due to toxicity and drug resistance. Thus,
      there is a continued need to discover new therapies. Recently evidences shows
      that pyrazoline derivatives are promising antitumor agents in many types of
      cancers, but there are no studies with bladder cancer. In order to find potent
      and novel chemotherapy drugs for bladder cancer, a series of pyrazoline
      derivatives 2a-2d were tested for their antitumor activity in two human bladder
      cancer cell lines 5647 and T24. The MTT assay showed that the compounds 1
      thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole (2a) and 1-thiocarbamoyl-5-(4
      chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (2c) decrease the cell viability
      of 5637 cells. Molecular modeling indicated that these compounds had a good oral
      bioavailability and low toxicities. Clonogenic assay and flow cytometric analysis
      were used to assess colony formation, apoptosis induction and cell cycle
      distribution. Overall, our results suggest that pyrazoline 2a and 2c, with the
      substituents hydrogen and chlorine respectively, may decrease cell viability and
      colony formation of bladder cancer 5637 cell line by inhibition of cell cycle
      progression, and for pyrazoline 2a, by induction of apoptosis. As indicated by
      the physicochemical properties of these compounds, the steric factor influences
      the activity. Therefore, these pyrazoline derivatives can be considered promising
      anticancer agents for the treatment of bladder cancer.

PMID- 28750359
TI  - Normal and anomalous heating rate effects on thermoluminescence of Ce-doped
      ZnB2O4.
AB  - The effect of heating rate (HR) on thermoluminescence (TL) glow curves of 1%, 4%,
      and 10% Ce3 + doped ZnB2O4 phosphors was investigated in detail. The glow peaks
      are examined and, activation energy (E) and frequency factor (s) are determined
      by using various heating rate (VHR) method. In the obtained glow curves with nine
      different HRs between 2 and 10 degrees C/s, it was observed that the TL
      intensities of the first peaks of all three samples and the second peak of 10%
      Ce3 + doped sample decrease with increasing HR. The decrease in TL intensity was
      investigated whether it may be due to the presence of thermal quenching or not.
      On the other hand, the second glow peaks of 1, 4% Ce3 + doped ZnB2O4 phosphors
      show an anomalous TL behavior, which the probability of the radiative processes
      increases due to recombination of free electrons, so the TL intensity increases
      with the HR. The graphs of full width at the half maximum (FWHM) versus HR were
      also plotted to evaluate the influence of HR on TL intensity. In this paper, we
      suggest that the non-localized Schon - Klasens model may give an explanation for
      the second peaks of 1, 4% Ce3 + doped ZnB2O4 phosphors showing an unexpected
      increase with the increasing HR. In addition, the calculated E values of all
      doped phosphors were found similar in the range of 0.47-0.53eV for peak 1 and
      0.61-0.66eV for peak 2. However, s values of Ce3 + doped ZnB2O4 phosphors were
      found slightly different according to the dopant amount and the equation used.
      Furthermore, different amount of Ce3 + doped samples indicate the similar
      properties for the repeated cycles of 5Gy in the same irradiation conditions.

PMID- 28750360
TI  - Brain and skull base MRI findings in patients with Ollier-Maffucci disease: A
      series of 12 patient-cases.
AB  - OBJECTIVES: To estimate the prevalence rate of silent cranial and intracranial
      lesions in a series of Ollier-Maffucci patients. PATIENTS AND METHODS: Cerebral
      MRI was routinely performed in Ollier-Maffucci patients followed-up in our
      tertiary centers. Patients with previous history of skull base or intracranial
      tumors were excluded from the study. Clinical and radiological datas were
      retrospectively collected. The occurrence rate and nature of abnormal cerebral
      MRIs were determined. RESULTS: Twelve patients were included. A glioma-looking
      lesion was found in one patient (8%), while skull base lesions were evidenced in
      3 others (25%). A regular MRI follow-up was recommended for each patient, with a
      time interval varying between 1year and 3years depending on the likelihood of
      tumoral evolutivity, as infered from the MRI findings. CONCLUSION: All in all,
      the high rate of intracranial and skull base lesions with a malignant potential
      warrants to include cerebral MRI in the routine follow-up of Ollier-Maffucci
      patients.

PMID- 28750361
TI  - The influence of focused-attention meditation states on the cognitive control of
      sequence learning.
AB  - Cognitive control processes influence how motor sequence information is utilised
      and represented. Since cognitive control processes are shared amongst goal
      oriented tasks, motor sequence learning and performance might be influenced by
      preceding cognitive tasks such as focused-attention meditation (FAM). Prior to a
      serial reaction time task (SRTT), participants completed either a single-session
      of FAM, a single-session of FAM followed by delay (FAM+) or no meditation
      (CONTROL). Relative to CONTROL, FAM benefitted performance in early, random
      ordered blocks. However, across subsequent sequence learning blocks, FAM+
      supported the highest levels of performance improvement resulting in superior
      performance at the end of the SRTT. Performance following FAM+ demonstrated
      greater reliance on embedded sequence structures than FAM. These findings
      illustrate that increased top-down control immediately after FAM biases the
      implementation of stimulus-based planning. Introduction of a delay following FAM
      relaxes top-down control allowing for implementation of response-based planning
      resulting in sequence learning benefits.

PMID- 28750362
TI  - Removal behaviors of sulfamonomethoxine and its degradation intermediates in
      fresh aquaculture wastewater using zeolite/TiO2 composites.
AB  - Removal efficiencies of sulfamonomethoxine (SMM) and its degradation
      intermediates formed by treatment with zeolite/TiO2 composites through adsorption
      and photocatalysis were investigated in fresh aquaculture wastewater (FAWW).
      Coexistent substances in the FAWW showed no inhibitory effects against SMM
      adsorption. Although coexistent substances in the FAWW inhibited the
      photocatalytic decomposition of SMM, the composites mitigated the inhibition,
      possibly because of concentration of SMM on their surface by adsorption. LC/MS/MS
      analyses revealed that hydroxylation of amino phenyl and pyrimidinyl portions,
      transformation of the amino group in the amino phenyl portion into a nitroso
      group, and substitution of the methoxy group with a hydroxyl group occurring in
      the initial reaction resulted in the formation of various intermediates during
      the photocatalysis of SMM. All detected intermediates had a ring structure, and
      almost all intermediates disappeared at the same time SMM was completely
      decomposed. Ph-OH formed by hydroxylation of the phenyl portion was detected upon
      decomposition of SMM during photocatalysis. The removal of Ph-OH by the
      composites proceeded more rapidly than that by TiO2 alone under ultraviolet
      irradiation. The SMM and Ph-OH were completely degraded by the composites within
      30min, showing that the zeolite/TiO2 composites were effective in removing SMM
      and its intermediates from FAWW.

PMID- 28750364
TI  - Deoxyelephantopin Induces Reactive Oxygen Species-Mediated Apoptosis and
      Autophagy in Human Osteosarcoma Cells.
AB  - BACKGROUND/AIMS: Osteosarcoma is the predominant form of primary bone malignancy.
      Although the combinational application of neoadjuvant chemotherapy and surgical
      resection significantly increases the survival rate, the therapeutic outcome
      remains unsatisfactory. Deoxyelephantopin (DET), an active ingredient of
      Elephantopus scaber, has been reported to have an anti-tumor effect in recent
      publications. This study aimed to investigate whether DET has antineoplastic
      effects on osteosarcoma cells and its underlying mechanism. METHODS: Cell
      viability and morphological changes were assessed by MTT and Live/dead assays.
      Cell apoptosis, reactive oxygen species (ROS) and mitochondrial membrane
      potential were detected utilizing Annexin V-FITC/PI double staining, DCFH-DA and
      JC-1 probes, respectively. Autophagy was detected by mRFP-GFP-LC3 adenovirus
      transfection and western blot. RESULTS: DET dose-dependently reduced the
      viability of osteosarcoma cells following the increase in intracellular ROS
      levels. Pretreatment with N-acetylcysteine (NAC) reversed this effect.
      Furthermore, DET induced mitochondrial apoptosis. Depolarized cells were
      increased, and apoptosis-related proteins, such as Bax, Bcl-2, cleaved caspase-9,
      cleaved caspase-3 and cleaved ploy ADP-ribose polymerase, were activated.
      Additionally, we found that DET could induce autophagy in osteosarcoma cells, but
      autophagy inhibition did not affect the decrease in cell viability. CONCLUSION:
      DET induced apoptosis in osteosarcoma cells through ROS generation, mitochondrial
      dysfunction and caspase activation; in addition, autophagy was involved in the
      effects of DET on osteosarcoma cells.

PMID- 28750365
TI  - A Novel Evaluation for Predicting Aortic Complicated Lesions Using Calcification
      on Chest X-ray.
AB  - BACKGROUND: The aorta is a significant source of cerebral thromboembolisms.
      Aortic complicated lesions (ACLs) are key findings on transesophageal
      echocardiography (TEE) for assessing aortic sources of emboli to the brain. TEE
      is sometimes avoided due to its invasiveness. However, few reports have examined
      alternative methods for predicting ACLs. We investigated relationships between
      aortic arch calcification (AAC) on chest X-ray and ACLs. METHODS: Participants
      comprised 300 patients with acute ischemic stroke or transient ischemic attack
      who underwent TEE for the evaluation of the aortic arch and heart. A postero
      anterior plain chest X-ray in the recumbent position was evaluated on admission
      for each patient. AAC was evaluated using 4 grades (0-3) and "AAC thickness"
      defined as the distance from the inner margin of the most distant AAC to the
      outer margin of the aortic vessel wall. ACLs were defined by intima-media
      thickness (IMT) >=4.0 mm or presence of ulcerated or mobile plaques. Carotid
      maximum IMT on ultrasonography was also evaluated. Comparison of the diagnostic
      ability to predict ACL was performed between AAC grades and AAC thickness or AAC
      thickness and carotid maximum IMT using the Delong method. RESULTS: ACLs were
      identified in 71 patients (23.7%), including ACLs with ulcerated plaques in 24
      (8.0%) and ACLs with mobile plaques in 9 (3.0%). Plaque thickness was greater in
      higher AAC grades or higher quartiles of AAC thickness (p for trend <0.001 each).
      The Cochran-Armitage test showed that both higher AAC grade and higher quartile
      of AAC thickness were significantly associated with the presence of ACLs, as well
      as the presence of ulcerated or mobile plaques (p for trend < 0.001 each).
      Receiver-operating characteristic (ROC) analysis showed optimal cut-off values
      for AAC thickness of 5.6 mm for ACLs and 6.0 mm for ulcerated or mobile plaques.
      Multivariate logistic regression revealed a higher grade of AAC (grades 2-3) and
      AAC thickness (>=6 mm) as significantly associated with ACLs and ulcerated or
      mobile plaques (p < 0.001 each). ROC curve comparisons showed that AAC thickness
      offered a better marker of ACLs than AAC grade (p = 0.019), although no
      significant difference was evident between AAC thickness and carotid maximum IMT
      (p = 0.567). CONCLUSIONS: AAC on chest X-ray, evaluated by both AAC grade and AAC
      thickness to the outer aortic vessel wall, was significantly associated with ACLs
      on TEE. AAC thickness was suggested as more useful than AAC grade and equivalent
      to carotid IMT in predicting ACLs.

PMID- 28750366
TI  - Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia
      Reperfusion Injury in Sprague Dawley Rats.
AB  - BACKGROUND: Hepatic ischemia reperfusion is one the main causes for graft failure
      following transplantation. Although, the molecular events that lead to hepatic
      failure following ischemia reperfusion (IR) are diverse and complex, previous
      studies have shown that excessive formation of reactive oxygen species (ROS) are
      responsible for hepatic IR injury. Cerium oxide (CeO2) nanoparticles have been
      previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we
      evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia
      reperfusion injury. METHODS: Male Sprague Dawley rats were randomly assigned to
      one of the four groups: Control, CeO2 nanoparticle only, hepatic ischemia
      reperfusion (IR) group and hepatic ischemia reperfusion (IR) plus CeO2
      nanoparticle group (IR+ CeO2). Partial warm hepatic ischemia was induced in left
      lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were
      sacrificed after 6h of reperfusion and blood and tissue samples were collected
      and processed for various biochemical experiments. RESULTS: Prophylactic
      treatment with CeO2 nanoparticles (0.5mg/kg i.v (IR+CeO2 group)) 1 hour prior to
      hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum
      levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after
      reperfusion. These changes were accompanied by significant decrease in hepatocyte
      necrosis along with reduction in several serum inflammatory markers such as
      macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO,
      myoglobin and plasminogen activator inhibitor-1. However, immunoblotting
      demonstrated no significant changes in the levels of apoptosis related protein
      markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours
      suggesting necrosis as the main pathway for hepatocyte death. CONCLUSION: Taken
      together, these data suggest that CeO2 nanoparticles attenuate IR induced cell
      death and can be used as a prophylactic agent to prevent hepatic injury
      associated with graft failure.

PMID- 28750367
TI  - Challenges Associated with Managing End-Stage Renal Disease in Extremely Morbid
      Obese Patients: Case Series and Literature Review.
AB  - Obesity has grown into an epidemic across the globe. Mirroring this growth in the
      number of obese individuals in the general population, the prevalence of obesity
      and extremely morbid obesity (body mass index >50 kg/m2) is similarly rising in
      patients with end-stage renal disease (ESRD). Obesity, and more so, extremely
      morbid obesity, creates additional challenges for clinicians aiming at providing
      the best treatment options to patients with ESRD. Although literature is
      available regarding renal replacement therapy (RRT) for obese patients,
      literature about challenges facing clinicians managing ESRD in the extremely
      obese patients is lacking. Furthermore, the optimal strategies and goals for
      managing these patients with ESRD are not well defined. To our knowledge, no
      study has been done evaluating RRT options available to extremely morbid obese
      patients and the challenges associated with these options. Here, we report a case
      series and discuss the potential challenges faced by extremely obese patients
      with ESRD requiring RRT.

PMID- 28750368
TI  - Changes in White Matter Integrity following Intensive Voice Treatment (LSVT
      LOUD(r)) in Children with Cerebral Palsy and Motor Speech Disorders.
AB  - Preliminary evidence suggests that intensive voice and speech treatment based on
      activity-dependent neuroplasticity principles holds promise for affecting
      positive change in children with cerebral palsy (CP) and motor speech disorders.
      Diffusion tensor imaging (DTI) allows researchers to make inferences about the
      integrity of white matter tracks and provides a sensitive measure of
      neuroplasticity. Previous treatment studies looking at the effects of training on
      white matter integrity have shown positive results, but these studies have been
      limited to gross motor function. Eight children with motor speech disorders and
      CP (3 females; age 8-16 years) and an age- and sex-matched group of typically
      developing (TD) children participated. Each child with CP completed a full dose
      of LSVT LOUD(r) and a 12-week maintenance program. Participants attended 3
      recording sessions: before and after treatment, and after the maintenance period.
      TD children were tested at the same 3 time points. Recording sessions for both
      groups of children included measures of white matter integrity using DTI and
      acoustic measures of voice and speech. Fractional anisotropy (FA) was measured
      for 2 motor tracts and 5 association tracts. In children with CP, we observed an
      increase in FA in several motor and association tracts immediately following
      treatment and 12 weeks after treatment. Acoustic data on untrained tasks were
      correlated with changes in FA detected immediately following treatment and after
      the 12-week maintenance program. These findings suggest that long-term practice
      of skills attained during the treatment phase enhances white matter tract
      integrity in speech production networks.

PMID- 28750369
TI  - Matrix Metalloproteinase Polymorphisms in Patients with Floppy Mitral
      Valve/Mitral Valve Prolapse (FMV/MVP) and FMV/MVP Syndrome.
AB  - BACKGROUND: It has been suggested that collagen abnormalities of the mitral valve
      are present in patients with floppy mitral valve (FMV)/mitral valve prolapse
      (MVP). Genetic factors determining collagen synthesis and degradation have not
      been well defined in these patients. This study was undertaken to determine
      whether selective polymorphisms of matrix metalloproteinase-2 (MMP2) or
      transforming growth factor-beta (TGFbeta), with known or putative effects on
      collagen turnover, are more frequent in FMV/MVP. METHODS: Single nucleotide
      polymorphisms (SNPs) in select genes related to collagen turnover, including MMP2
      rs2285053, MMP2 rs243865, TGFbeta1 rs1800469, and TGFbeta2 rs900, were determined
      in 98 patients with FMV/MVP who had severe mitral regurgitation and compared to
      99 controls. RESULTS: MMP2 rs243865 was the only SNP significantly associated
      with FMV/MVP as compared to the control (odds ratio 2.07, 95% CI 1.23-3.50, p =
      0.006). MMP2 rs228503 was the only SNP significantly associated with the FMV/MVP
      syndrome as compared to patients with FMV/MVP without the syndrome (odds ratio
      2.41, 95% CI 1.08-5.40, p = 0.032). CONCLUSION: The frequency of certain MMP2
      polymorphisms is higher in patients with the FMV/MVP syndrome and patients with
      FMV/MVP without the syndrome. The data suggest that a genetic predisposition that
      alters collagen turnover may play a role in the pathogenesis and development of
      FMV/MVP.

PMID- 28750370
TI  - Social Birth: Rites of Passage for the Newborn.
AB  - Rites of passage mark important changes during human life and, for the neonate,
      its transition from intrauterine life into society. Their original intent was to
      purify the body from blood and meconium. But the cleansing rites had a spiritual
      dimension from the very start. When the rites of Mesopotamian, Egyptian, Jewish,
      Greek, Roman, Hindu, Nordic, Muslim, Maya, and Christian cultures are briefly
      compared, they reveal a remarkable similarity. What most rites had in common was
      the cleansing of the body, or sprinkling it with water; special clothing; the
      exorcism of evil spirits; blessings and prayers for good spirits; and a name
      giving ceremony and a feast for family, relatives, and friends. Before this rite,
      the infant's social existence was incomplete and it could easily be abandoned or
      killed, as was usual in cases of severe malformations. Infant baptism originated
      in the 4th century CE with the concept of original sin. Emergency baptism
      originated in the 12th century and had a profound influence on the development of
      obstetrics and neonatal care. Rites of passage defined, but also set an end to,
      the liminal status between life and death in a phase of high mortality and
      partial personhood, and granted the right to live for the infant.

PMID- 28750371
TI  - Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery
      Constriction.
AB  - BACKGROUND/AIMS: Endothelin-1 is implicated in the pathogenesis of hypertension,
      but the underlying mechanisms remained elusive. Our previous study found that
      inhibition of mitochondrial fission of smooth muscle cells suppressed
      phenylephrine- and high K+-induced artery constriction. Here, we studied the
      effects of mitochondrial fission inhibitors on endothelin-1-induced
      vasoconstriction. METHODS: The tension of rat mesenteric arteries and thoracic
      aorta was measured by using a multi-wire myograph system. Mitochondrial
      morphology of aortic smooth muscle cells was observed by using transmission
      electron microscopy. RESULTS: Dynamin-related protein-1 selective inhibitor mdivi
      1 relaxed endothelin-1-induced constriction, and mdivi-1 pre-treatment prevented
      endothelin-1-induced constriction of rat mesenteric arteries with intact and
      denuded endothelium. Mdivi-1 had a similar inhibitory effect on rat thoracic
      aorta. Another mitochondrial fission inhibitor dynasore showed similar effects as
      mdivi-1 in rat mesenteric arteries. Mdivi-1 inhibited endothelin-1-induced
      increase of mitochondrial fission in smooth muscle cells of rat aorta. Rho
      associated protein kinase inhibitor Y-27632 which relaxed endothelin-1-induced
      vasoconstriction inhibited endothelin-1-induced mitochondrial fission in smooth
      muscle cells of rat aorta. CONCLUSION: Endothelin-1 increases mitochondrial
      fission in vascular smooth muscle cells, and mitochondrial fission inhibitors
      suppress endothelin-1-induced vasoconstriction.

PMID- 28750373
TI  - Principles in the Examination and Management of Soft Tissue Lesions.

PMID- 28750372
TI  - Contemporary Antiplatelet Treatment in Acute Coronary Syndrome Patients with
      Impaired Renal Function Undergoing Percutaneous Coronary Intervention.
AB  - OBJECTIVES: To assess the clinical impact of impaired renal function (IRF), in
      "real-world" acute coronary syndrome (ACS) patients, receiving clopidogrel,
      prasugrel, or ticagrelor. METHODS: This was a prospective, observational,
      multicenter, cohort study of ACS patients undergoing percutaneous coronary
      interventions (PCI) with IRF (creatinine clearance <60 mL/min by Cockroft-Gault
      equation), who were recruited into the Greek Antiplatelet Registry (GRAPE).
      Patients were followed-up until 1 year for major adverse cardiovascular events
      (MACE; a composite of death, nonfatal myocardial infarction, urgent
      revascularization, and stroke) and BARC (Bleeding Academic Research Consortium)
      bleeding. RESULTS: Out of 2,047 registered patients, there were 344 (16.8%) with
      IRF. At the 1-year follow-up, MACE occurred in 18.6 and 6.2% of those patients
      with and without IRF, respectively: adjusted hazard ratio (HR) = 2.13 (95%
      confidence interval, CI 1.16-3.91), p = 0.02. IRF patients were also at higher
      risk of death and BARC type >=2 and >=3 bleeding: adjusted HR = 3.55 (95% CI 1.73
      7.27), p = 0.001; HR = 2.75 (95% CI 1.13-6.68), p = 0.03; and HR = 6.02 (95% CI
      2.30-15.77), p < 0.001, respectively. Combined MACE and BARC type >=2 bleeding
      occurred in 34.0 and 14.0% of those with and without IRF, respectively: adjusted
      HR = 2.65 (95% CI 1.36-5.16), p = 0.004. At discharge, clopidogrel was more
      frequently prescribed in IRF patients (61.0 vs. 33.1%, p < 0.001). CONCLUSIONS:
      Real-world ACS patients with IRF subjected to PCI demonstrate higher thrombotic
      and bleeding risks than patients with normal renal function.

PMID- 28750374
TI  - Sampling and Preparation Techniques.

PMID- 28750375
TI  - Ancillary Techniques.

PMID- 28750376
TI  - Normal Elements and the Cytologic Features of Reactive Changes in Soft Tissue.

PMID- 28750377
TI  - Adipocytic Tumors.

PMID- 28750378
TI  - Fibroblastic/Myofibroblastic Tumors.

PMID- 28750380
TI  - Smooth-Muscle Tumors.

PMID- 28750379
TI  - So-Called Fibrohistiocytic Tumors.

PMID- 28750381
TI  - Pericytic (Perivascular) Tumors.

PMID- 28750382
TI  - Skeletal-Muscle Tumors.

PMID- 28750383
TI  - Vascular Tumors.

PMID- 28750384
TI  - Gastrointestinal Stromal Tumor.

PMID- 28750385
TI  - Nerve Sheath Tumors.

PMID- 28750386
TI  - Tumors of Uncertain Differentiation.

PMID- 28750387
TI  - Undifferentiated/Unclassified Sarcomas.

PMID- 28750388
TI  - Neuroectodermal Tumors.

PMID- 28750389
TI  - Principles in the Examination and Management of Bone Neoplasms; Normal Elements
      and the Cytologic Features of Reactive Changes in the Bone.

PMID- 28750390
TI  - Osteogenic Tumors.

PMID- 28750392
TI  - Giant Cell Tumor of Bone and Other Giant Cell-Rich Lesions.

PMID- 28750391
TI  - Ewing Sarcoma.

PMID- 28750393
TI  - Notochordal Tumors.

PMID- 28750394
TI  - Lymphohematopoietic and Histiocytic Tumors.

PMID- 28750396
TI  - Bone Lesions Rarely Examined by Fine-Needle Aspiration.

PMID- 28750395
TI  - Bone Metastases.

PMID- 28750397
TI  - Cartilaginous Tumors.

PMID- 28750399
TI  - Communication Skills Trainings: Subjective Appraisal of Physicians from Five
      Cancer Centres in North Rhine, Germany.
AB  - BACKGROUND: Physician-patient communication is an essential component of high
      quality health care provision for cancer patients. To date, communication skills
      training programmes have not been systematically implemented in oncology and have
      low physician participation rates. METHODS: As a part of a needs assessment a
      written questionnaire was used to explore needs and preferences (structural
      conditions and content) regarding communication skills training programmes for
      physicians working in oncology settings in 5 university hospitals in North Rhine,
      Germany. RESULTS: 207 physicians took part in the survey. Analyses revealed
      positive attitudes and high willingness to attend such training programmes, with
      a preference for short trainings that are compatible with clinical practice.
      Suggested topics included breaking bad news, conversations about death and dying
      and dealing with difficult emotions. CONCLUSION: Communication skills training
      approaches should not only pay attention to evidence regarding their efficacy,
      but also take into consideration physicians' needs and preferences. Further
      research is required on the subject of barriers to participation in such training
      programmes.

PMID- 28750400
TI  - A Dopamine Hypothesis of Autism Spectrum Disorder.
AB  - Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders
      characterized by social deficits and stereotyped behaviors. While several
      theories have emerged, the pathogenesis of ASD remains unknown. Although studies
      report dopamine signaling abnormalities in autistic patients, a coherent dopamine
      hypothesis which could link neurobiology to behavior in ASD is currently lacking.
      In this paper, we present such a hypothesis by proposing that autistic behavior
      arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that
      a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a
      dysfunction of the nigrostriatal circuit leads to stereotyped behaviors.
      Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on
      clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions
      in the same circuits should associate with autistic-like behavior in nonautistic
      subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune
      neuropsychiatric disorder associated with streptococcal infections) which
      displays behaviors similar to those of ASD, presumed to arise from dopaminergic
      dysfunctions. Second, we argue that providing dopamine modulators to autistic
      subjects should lead to a behavioral improvement. Regarding this, we present
      clinical studies of dopamine antagonists which seem to have improving effects on
      autistic behavior. Furthermore, we explore the means of testing our hypothesis by
      using neuroreceptor imaging, which could provide comprehensive evidence for
      dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the
      limitations of our hypothesis. Along these lines, we aim to provide a
      dopaminergic model of ASD which might lead to a better understanding of the ASD
      pathogenesis.

PMID- 28750401
TI  - A Practical Approach to Tumor Heterogeneity in Clinical Research and Diagnostics.
AB  - This Pathobiology issue tries to better define the complex phenomenon of
      intratumor heterogeneity (ITH), mostly from a practical point of view. This topic
      has been chosen because ITH is a central issue in tumor development and has to be
      investigated directly in patient tissue and immediately applied in the treatment
      of the presenting patient. Different types of ITH should be considered: clonal
      genetic and epigenetic evolution, morphological heterogeneity, and tumor
      sampling, heterogeneity resulting from microenvironmental autocrine and paracrine
      interaction, and stochastic plasticity related to different functional cell
      efficiencies. For a higher level of reproducibility in clinical research and
      diagnostics, it is necessary to establish standardized analytical methods,
      including microdissection. In situ techniques can be pivotal to explore tumor
      microenvironment and can be improved with associated digital analysis. Liquid
      biopsies for plasma DNA analysis are at present the best method to study
      recurrent tumors with treatment adaptation, and widespread clinical use could be
      beneficial. The different types of tumor genomic instabilities could have
      pragmatic applications to rank ITH for clinical applications: treatment
      approaches differ in patients with a high nucleotide mutation rate and patients
      with high copy number alterations.

PMID- 28750402
TI  - Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells.
AB  - BACKGROUND/AIMS: The effects of zinc signaling on proliferation or apoptosis of
      leukemia cells remain elusive. In the present study, we used N, N, N', N'
      tetrakis-(2-pyridylmethyl)-ethylene-diamine (TPEN), a membrane-permeable zinc
      chelator, to evaluate the effect of zinc depletion on survival and apoptosis of
      NB4 acute promyelocytic leukemia (APL) cells. METHODS: The pro-apoptotic effects
      of TPEN on NB4 cells were examined by flow cytometry, and observed using an
      optical microscope. Intracellular labile zinc, nitric oxide (NO) or reactive
      oxygen species (ROS) changes caused by TPEN were measured by flow cytometry. We
      then explored possible roles of the crosstalk between intracellular labile zinc
      signaling and nitric oxide signaling in TPEN-triggered apoptosis. RESULTS: we
      found that TPEN induced apoptosis in NB4 APL cells in a dosage-dependent manner.
      We further demonstrated that TPEN triggered apoptosis by attenuating
      intracellular zinc and nitric oxide signaling in NB4 cells. Both exogenous zinc
      supplement and the nitric donor sodium nitroprusside (SNP) pre-incubation
      reversed TPEN-mediated inhibition of intracellular NO and Zn2+ signaling, and
      rescued NB4 cells from apoptosis. CONCLUSION: These results suggest for the first
      time that crosstalk between zinc signaling and nitric oxide pathway is essential
      for the survival of NB4 cells. TPEN induces apoptosis in NB4 cells via negatively
      regulating intracellular NO and Zn2+ signaling. Our in vitro data suggest that
      zinc depletion by TPEN may be a potential therapeutic strategy for APL.

PMID- 28750403
TI  - Ablation of the Cl-/HCO3- Exchanger Pendrin Enhances Hydrochlorothiazide-Induced
      Diuresis.
AB  - BACKGROUND/AIMS: The Cl-/HCO3- exchanger pendrin and the thiazide-sensitive Na-Cl
      cotransporter NCC are expressed in the kidney distal nephron and mediate salt
      absorption. We hypothesized that deletion of pendrin leaves NCC as the major salt
      absorbing transporter in the distal nephron and therefore enhances salt excretion
      by hydrochlorothiazide (HCTZ). METHODS: Metabolic cage studies were performed in
      wild type, pendrin KO and NCC KO mice at baseline and following HCTZ treatment.
      In parallel studies, systemic blood pressure was measured in mice treated with
      HCTZ with the tail cuff method. RESULTS: Urine output, salt excretion and water
      intake were comparable in all groups under baseline condition. Urine output and
      water intake increased significantly only in pendrin KO mice in response to HCTZ,
      but not in WT or NCC KO mice. Sodium and chloride excretion increased in HCTZ
      treated pendrin KO mice, but they remained unchanged in WT or NCC KO mice.
      Pendrin KO mice treated with HCTZ developed volume depletion, as determined by
      increased expression of renin mRNA and protein. The expression of ENaC and
      pendrin increased in HCTZ-treated WT mice. HCTZ treatment did not significantly
      modify blood pressure in any of the experimental group. CONCLUSION: The ablation
      of the Cl-/HCO3- exchanger Pendrin enhances the magnitude of salt wasting by
      HCTZ.

PMID- 28750404
TI  - Altered Global 5-Hydroxymethylation Status in Hidradenitis Suppurativa: Support
      for an Epigenetic Background.
AB  - BACKGROUND: The pathogenesis of hidradenitis suppurativa (HS), with its complex
      inflammatory network, is still elusive. Imbalances in DNA methylation can lead to
      genome destabilization and have been assumed to play a role in inflammatory
      diseases. Global DNA methylation and hydroxymethylation have not been studied in
      HS yet. OBJECTIVE: We conducted this study to investigate the global DNA
      methylation and hydroxymethylation status in lesional and perilesional HS skin
      compared to healthy controls. METHODS: Immunohistochemical analysis was performed
      for 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in 30 lesional
      and 30 corresponding healthy-appearing perilesional HS tissue samples. We
      included 30 healthy subjects as an interindividual control group. RESULTS: 5-hmC
      levels were significantly lower in healthy-appearing perilesional (p < 0.0001)
      and lesional HS skin (p < 0.0001) when compared to healthy controls. There was no
      significant difference between lesional HS skin and perilesional HS skin
      regarding 5-hmC levels (p = 0.6654). In contrast to 5-hmC, 5-mC staining showed
      no significant changes between the 3 groups. Univariate analysis revealed no
      significant association between patients' characteristics, disease severity, and
      the levels of 5-mC and 5-hmC. CONCLUSION: Our findings indicate that imbalances
      in DNA hydroxymethylation may play a role in the pathogenesis of HS rather than
      DNA methylation. Further studies are warranted to investigate the significance of
      DNA hydroxymethylation and the regulating enzymes in HS in order to advance our
      knowledge of the inflammatory network in this disease.

PMID- 28750405
TI  - Untargeted DNA-Demethylation Therapy Neither Prevents Nor Attenuates Ischemia
      Reperfusion-Induced Renal Fibrosis.
AB  - BACKGROUND: Current treatment options for chronic kidney disease (CKD) are
      limited and their focus is on slowing its progression by addressing
      comorbidities. Fibrosis, the common histopathological process in CKD, is a major
      therapeutic research target. In CKD, fibroblasts are terminally activated due to
      alterations in their DNA-methylation pattern, particularly hypermethylation.
      Preventing the copying of pathological DNA-methylation patterns in proliferating
      fibroblasts could be a new effective therapeutic strategy for treating CKD.
      METHODS: To evaluate the therapeutic effect of short-term treatment with the DNA
      methyltransferase (DNMT)-inhibitor decitabine on fibrosis (either developing or
      already established), male C57Bl/6 mice underwent warm unilateral ischemia
      reperfusion injury. Respectively 3 days, 3 and 6 weeks after surgery, decitabine
      treatment (0.25 mg/kg) was initiated for 10 days after which animals were
      followed up to 12 weeks after ischemia. The efficacy of therapy on fibrosis was
      evaluated by collagen I and tgfbeta gene expression and histological
      quantification of collagen I staining. In addition, the effect of decitabine
      treatment on tubular injury (Kim-1, Ngal), inflammation (TNFa, IL6), DNA
      methyltransferases (Dnmt1, 3a, and 3b), and global methylation status was
      determined. RESULTS: Following ischemia there was a significant increase in
      fibrotic, injury, and inflammatory markers as well as an increase of the various
      dnmts. Although decitabine treatment transiently increased renal injury and had a
      moderately decreasing effect on dnmt expression and on global DNA-methylation
      upon immediate treatment, none of the treatment regimens succeeded in preventing,
      attenuating, or diminishing fibrosis in the long run. CONCLUSION: Administration
      of untargeted nucleoside analogues seems unsuitable as a first-line treatment
      option in developing or established CKD.

PMID- 28750406
TI  - A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal
      Abnormalities in GLUT4 +/- Male Mice.
AB  - BACKGROUND/AIMS: Altered nutrients during the in utero (IU) and/or lactation (L)
      period predispose offspring to cardio-renal diseases in adulthood. This study
      investigates the effect of a high fat diet (HFD) fed to female mice during IU/L
      on gene expression patterns associated with heart and kidney failure and
      hypertension in male offspring. METHODS: Female wild type (WT) mice were fed
      either a HFD or control chow (C) prior to mating with males with a genetic
      heterozygous deletion of GLUT4 (G4+/-, a model of peripheral insulin resistance
      and hypertension) and throughout IU/L. After weaning male offspring were placed
      on a standard rodent chow until 24 weeks of age. RESULTS: All offspring exposed
      to a maternal HFD showed increased heart and kidney weight and reduced cardiac
      insulin responsiveness. G4+/- offspring on a HFD displayed early hypertension
      associated with increased renal gene expression of renin and the AT1- receptors
      compared to G4+/- on a C diet. This group showed decreased cardiac expression of
      key genes involved in fatty acid oxidation compared to WT on a C diet.
      CONCLUSIONS: These results indicate an interaction between a HFD diet and
      genotype during early life development that can enhance susceptibility to cardio
      renal diseases later in life.

PMID- 28750407
TI  - In Individuals Following Aneurysmal Subarachnoid Haemorrhage, Hair Cortisol
      Concentrations Are Higher and More Strongly Associated with Psychological
      Functioning and Sleep Complaints than in Healthy Controls.
AB  - BACKGROUND: Following an aneurysmal subarachnoid haemorrhage (aSAH), many
      patients report persistent deficits in psychological functioning, characterised
      by high levels of stress and symptoms of depression, low life satisfaction, along
      with poor sleep. Such deficits have been associated with altered saliva and serum
      cortisol levels due to a dysregulation of hypothalamic-pituitary-adrenal axis
      activity (HPA-AA). However, hair cortisol concentrations (HCCs) have not been
      assessed in this population, although this method allows a long-term insight into
      cortisol values. Therefore, the objective of this study was to compare HCCs in
      aSAH patients and healthy controls and to examine how HCCs are associated with
      perceived stress, psychological functioning, and sleep complaints. METHODS: In
      this cross-sectional study, data on depressive symptoms, hypochondriacal beliefs,
      life satisfaction, and sleep complaints were gathered in 15 aSAH patients and 17
      healthy controls. HCCs of the previous 3 months were assessed. RESULTS: aSAH
      patients had significantly higher HCCs than healthy controls. In aSAH patients,
      higher HCCs were significantly associated with increased depressive symptoms,
      hypochondriacal beliefs, lower life satisfaction, and increased sleep complaints.
      Such significant associations were not found in healthy controls. CONCLUSIONS:
      Our findings indicate that a dysregulation of HPA-AA is associated with some of
      the long-term impairments in psychological functioning and sleep in aSAH
      survivors. While the direction of association remained unclear, a dysregulated
      HPA-AA may be causally linked with the maintenance of poor psychological
      functioning and poor sleep. The overall findings should be considered in the
      planning of long-term treatment aimed at improving psychological functioning and
      sleep in aSAH patients.

PMID- 28750408
TI  - Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In
      Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition.
AB  - BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT) is recognized as a
      crucial mechanism in breast cancer progression and metastasis. Paired-related
      homeobox 2 (Prrx2) has been identified as a new EMT inducer in cancer, but the
      underlying mechanisms are still poorly understood. METHODS: The expression of
      Prrx2 was assessed by immunohistochemistry in breast cancer tissues to evaluate
      the clinicopathological significance of Prrx2, as well as the correlation between
      Prrx2 and EMT. Short hairpin RNA knockdown of Prrx2 was used to examine cellular
      effects of Prrx2, detecte the expression of Wnt/beta-catenin signaling and EMT
      associated proteins, and observe cell proliferation, invasion and migration
      abilities in vitro and in vivo. RESULTS: Clinical association studies showed that
      Prrx2 expression was related to tumor size, lymph node metastasis, tumor node
      metastasis stages, EMT and poor survival. Results also showed that knockdown of
      Prrx2 could alter cell morphology, suppressed the abilities of cell
      proliferation, invasion and migration in breast cancer. Moreover, silencing of
      Prrx2 induced the mesenchymal-epithelial transition and prevented nuclear
      translocation of beta-catenin, inhibited wnt/beta-catenin signaling pathway.
      CONCLUSION: Our study indicated that Prrx2 may be an important activator of EMT
      in human breast cancer and it can serve as a molecular target of therapeutic
      interventions for breast cancer.

PMID- 28750409
TI  - TIMP-2*IGFBP7 (Nephrocheck(r)) Measurements at Intensive Care Unit Admission
      After Cardiac Surgery are Predictive for Acute Kidney Injury Within 48 Hours.
AB  - BACKGROUND/AIMS: Acute kidney injury (AKI) is a postoperative complication after
      cardiac surgery with a high impact on mortality and morbidity. Nephrocheck(r)
      [TIMP-2*IGFBP7] determines markers of tubular stress, which occurs prior to
      tubular damage. It is unknown at which time-point [TIMP-2*IGFBP7] measurement
      should be performed to ideally predict AKI. We investigated the association of
      [TIMP-2*IGFBP7] at various time-points with the incidence of AKI in patients
      undergoing elective cardiac surgery including cardio-pulmonary bypass. METHODS:
      In a prospective cohort study, serial blood and urine samples were collected from
      150 patients: pre-operative, at ICU-admission, 24h and 48h post-surgery. AKI was
      defined as Serum-Creatinine rise >0.3 mg/dl within 48hrs. Urinary [TIMP-2*IGFBP7]
      was measured at pre-operative, ICU-admission and 24h post-surgery; medical staff
      was kept blinded to these results. RESULTS: A total of 35 patients (23.5%)
      experienced AKI, with a higher incidence in those with high [TIMP-2*IGFBP7]
      values at ICU admission (57.1% vs. 10.1%, p<0.001). In logistic regression [TIMP
      2*IGFBP7] at ICU admission was independently associated with the occurrence of
      AKI (Odds Ratio 11.83; p<0.001, C-statistic= 0.74) after adjustment for EuroSCORE
      II and CBP-time. CONCLUSIONS: Early detection of elevated [TIMP-2*IGFBP7] at ICU
      admission was strongly predictive for postoperative AKI and appeared to be more
      precise as compared to subsequent measurements.

PMID- 28750411
TI  - EURenOmics Joint Annual Meeting. May 3-5, 2017, Berlin, Germany: Abstracts.

PMID- 28750410
TI  - Loss of the Protein Cystathionine beta-Synthase During Kidney Injury Promotes
      Renal Tubulointerstitial Fibrosis.
AB  - BACKGROUND/AIMS: Renal tubulointerstitial fibrosis (TIF) is the common pathway of
      progressive chronic kidney disease. Inflammation has been widely accepted as the
      major driving force of TIF. Cystathionine beta-synthase (CBS) is the first and
      rate-limiting enzyme in the transsulfuration pathway. CBS is considered to play
      protective role in liver and pulmonary fibrosis, but its role in TIF remains
      unknown. The purpose of this study was to investigate the potential role and
      mechanism of CBS in renal inflammation and TIF. METHODS: Renal function,
      tubulointerstitium damage index score, extracellular matrix (ECM) deposition, and
      the expressions of collagen I, collagen III, fibronectin, CD3, CD68, IL-1beta,
      TNF-alpha were measured in sham operation and unilateral ureteral obstruction
      (UUO) rats. Proteomics and gene array analysis were performed to screen
      differentially expressed molecules in the development of renal inflammation and
      TIF in UUO rats. The expression of CBS was detected in patients with obstructive
      nephropathy and UUO rats. We confirmed the expression of CBS using western blot
      and real-time PCR in HK-2 cells. Overexpression plasmid and siRNA were
      transfected specifically to study the possible function of CBS in HK-2 cells.
      RESULTS: Abundant expression of CBS, localized in renal tubular epithelial cells,
      was revealed in human and rat renal tissue, which correlated negatively with the
      progression of fibrotic disease. Expression of CBS was dramatically decreased in
      the obstructed kidney from UUO rats as compared with the sham group (SHM). In
      addition, knocking down CBS exacerbated extracellular matrix (ECM) deposition,
      whereas CBS overexpression attenuated TGF-beta1-induced ECM deposition in vitro.
      Inflammatory and chemotactic factors were also increased in CBS knockdown HK-2
      cells stimulated by IL-1beta. CONCLUSIONS: These findings establish CBS as a
      novel inhibitor in renal fibrosis and as a new therapeutic target in patients
      with chronic kidney disease.

PMID- 28750412
TI  - Where are the vertebras?

PMID- 28750413
TI  - In Vivo Imaging of Retinal Hypoxia Using HYPOX-4-Dependent Fluorescence in a
      Mouse Model of Laser-Induced Retinal Vein Occlusion (RVO).
AB  - Purpose: To demonstrate the utility of a novel in vivo molecular imaging probe,
      HYPOX-4, to detect and image retinal hypoxia in real time, in a mouse model of
      retinal vein occlusion (RVO). Methods: Retinal vein occlusion was achieved in
      adult mice by photodynamic retinal vein thrombosis (PRVT). One or two major
      retinal vein(s) was/were occluded in close proximity to the optic nerve head
      (ONH). In vivo imaging of retinal hypoxia was performed using, HYPOX-4, an
      imaging probe developed by our laboratory. Pimonidazole-adduct immunostaining was
      performed and used as a standard ex vivo method for the detection of retinal
      hypoxia in this mouse RVO model. The retinal vasculature was imaged using
      fluorescein angiography (FA) and isolectin B4 staining. Retinal thickness was
      assessed by spectral-domain optical coherence tomography (SD-OCT) analysis.
      Results: By application of the standard ex vivo pimonidazole-adduct
      immunostaining technique, retinal hypoxia was observed within 2 hours post-PRVT.
      The observed hypoxic retinal areas depended on whether one or two retinal vein(s)
      was/were occluded. Similar areas of hypoxia were imaged in vivo using HYPOX-4.
      Using OCT, retinal edema was observed immediately post-PRVT induction, resolving
      8 days later. Nominal preretinal neovascularization was observed at 10 to 14 days
      post-RVO. Conclusions: HYPOX-4 is an efficient probe capable of imaging retinal
      hypoxia in vivo, in RVO mice. Future studies will focus on its use in correlating
      retinal hypoxia to the onset and progression of ischemic vasculopathies.

PMID- 28750414
TI  - Retinal Vessel Geometry and the Incidence and Progression of Diabetic
      Retinopathy.
AB  - Purpose: To analyze the associations between retinal vessel geometry and the 1
      year incidence and progression of diabetic retinopathy (DR) in a Chinese
      population. Methods: This was a prospective cohort study of adult subjects with
      diabetes mellitus. Retinal vascular geometry was quantified from fundus
      photographs using a semiautomated computer-assisted program. Diabetic retinopathy
      was graded from retinal photographs at baseline and 1 year. Incident DR and 2
      step change in DR were analyzed. Results: In total, 249 subjects were included.
      Their mean age was 59.9 +/- 8.9 years, 74% were male, and the mean glycated
      hemoglobin A1c (HbA1C) and duration of diabetes were 7.7 +/- 1.4% and 14.3 +/-
      10.6 years, respectively. The distribution of DR severity at baseline was no DR
      in 35.7%, minimal nonproliferative diabetic retinopathy (NPDR) in 15.3%, mild
      NPDR in 14.6%, moderate NPDR in 23.1%, severe NPDR in 5.1%, and proliferative DR
      in 6.1% of eyes. In multivariate analyses adjusting for age, duration of
      diabetes, sex, smoking status, HbA1c, hypertension, and hyperlipidemia, subjects
      with higher venular fractal dimensions were more likely to have incident DR (odds
      ratio [OR] 0.38, [95% confidence interval (CI), 0.15-0.96], P = 0.032, per SD
      decrease). Lower venular tortuosity was associated with a lower likelihood of DR
      progression (OR 0.76, [95% CI, 0.59-0.97], P = 0.005, per SD decrease). Lower
      arteriolar tortuosity was associated with a greater likelihood of DR regression
      (OR 1.95, [95% CI 1.07-3.56], P = 0.037, per SD decrease). Conclusions: Novel
      measures of retinal vascular geometry are associated with the incidence and
      progression of DR at 1 year. These geometric measures are likely to represent
      early dysfunction in the retinal microvasculature.

PMID- 28750415
TI  - Influences of Phonological Context on Tense Marking in Spanish-English Dual
      Language Learners.
AB  - Purpose: The emergence of tense-morpheme marking during language acquisition is
      highly variable, which confounds the use of tense marking as a diagnostic
      indicator of language impairment in linguistically diverse populations. In this
      study, we seek to better understand tense-marking patterns in young bilingual
      children by comparing phonological influences on marking of 2 word-final tense
      morphemes. Method: In spontaneous connected speech samples from 10 Spanish
      English dual language learners aged 56-66 months (M = 61.7, SD = 3.4), we
      examined marking rates of past tense -ed and third person singular -s morphemes
      in different environments, using multiple measures of phonological context.
      Results: Both morphemes were found to exhibit notably contrastive marking
      patterns in some contexts. Each was most sensitive to a different combination of
      phonological influences in the verb stem and the following word. Conclusions:
      These findings extend existing evidence from monolingual speakers for the
      influence of word-final phonological context on morpheme production to a
      bilingual population. Further, novel findings not yet attested in previous
      research support an expanded consideration of phonological context in clinical
      decision making and future research related to word-final morphology.

PMID- 28750416
TI  - Electrophysiological Evidence for the Sources of the Masking Level Difference.
AB  - Purpose: The purpose of this review article is to review evidence from auditory
      evoked potential studies to describe the contributions of the auditory brainstem
      and cortex to the generation of the masking level difference (MLD). Method: A
      literature review was performed, focusing on the auditory brainstem, middle, and
      late latency responses used in protocols similar to those used to generate the
      behavioral MLD. Results: Temporal coding of the signals necessary for generating
      the MLD occurs in the auditory periphery and brainstem. Brainstem disorders up to
      wave III of the auditory brainstem response (ABR) can disrupt the MLD. The full
      MLD requires input to the generators of the auditory late latency potentials to
      produce all characteristics of the MLD; these characteristics include threshold
      differences for various binaural signal and noise conditions. Studies using
      central auditory lesions are beginning to identify the cortical effects on the
      MLD. Conclusions: The MLD requires auditory processing from the periphery to
      cortical areas. A healthy auditory periphery and brainstem codes temporal
      synchrony, which is essential for the ABR. Threshold differences require engaging
      cortical function beyond the primary auditory cortex. More studies using cortical
      lesions and evoked potentials or imaging should clarify the specific cortical
      areas involved in the MLD.

PMID- 28750417
TI  - Prediction of potentially avoidable readmission risk in a division of general
      internal medicine.
AB  - INTRODUCTION: The 30-day post-discharge readmission rate is a quality indicator
      that may reflect suboptimal care. The computerised algorithm SQLape(r) can
      retrospectively identify a potentially avoidable readmission (PARA) with high
      sensitivity and specificity. We retrospectively analysed the hospital stays of
      patients readmitted to the Department of Internal Medicine of the CHUV (Centre
      Hospitalier Universitaire Vaudois) in order to quantify the proportion of PARAs
      and derive a risk prediction model. METHOD: All hospitalisations between January
      2009 and December 2011 in our division of general internal medicine were
      analysed. Readmissions within 30 days of discharge were categorised using
      SQLape(r). The impact on PARAs was tested for various clinical and nonclinical
      factors. The performance of the developed model was compared with the well
      validated LACE and HOSPITAL scores. RESULTS: From a total of 11 074 hospital
      stays, 777 (7%) were followed with PARA within 30 days. By analysing a group of
      6729 eligible stays, defined in particular by the patients' returning to their
      place of residence (home or residential care centre), we identified the following
      risk factors: >=1 hospitalisation in the year preceding index admission, Charlson
      score >1, active cancer, hyponatraemia, length of stay >11 days, prescription of
      >=15 different medications during the stay. These variables were used to derive a
      risk prediction model for PARA with a good discriminatory power (C-statistic
      0.70) and calibration (p = 0.69). Patients were then classified as low (16.4%),
      intermediate (49.4%) or high (34.2%) risk of PARA. The estimated risk of PARA for
      each category was 3.5%, 8.7% and 19.6%, respectively. The LACE and the HOSPITAL
      scores were significantly correlated with the PARA risk. The discriminatory power
      of the LACE (C-statistic 0.61) and the HOSPITAL (C-statistic 0.54) were lower
      than our model. CONCLUSION: Our model identifies patients at high risk of 30-day
      PARA with a good performance. It could be used to target transition of care
      interventions. Nevertheless, this model should be validated on more data and
      could be improved with additional parameters. Our results highlight the
      difficulty to generalise one model in the context of different healthcare
      systems.

PMID- 28750418
TI  - Lower hospital volume is associated with higher mortality after oesophageal,
      gastric, pancreatic and rectal cancer resection.
AB  - BACKGROUND: In various countries, the association of lower hospital volume and
      higher mortality after oesophageal, gastric, pancreatic and rectal cancer
      resection has been clearly demonstrated. However, scientific evidence regarding
      the volume-outcomes relationship for high-risk visceral surgical procedures in
      Switzerland is lacking. The a priori hypothesis of this retrospective population
      based cohort study analysis was that low-volume hospitals in Switzerland have a
      higher rate of postoperative mortality after oesophageal, gastric, pancreatic and
      rectal cancer resection. METHODS: Patients undergoing elective resection of
      oesophageal, gastric, pancreatic and rectal cancer between 1999 and 2012 were
      identified in the inpatient database of the Swiss Federal Statistical Office.
      Nonparametric correlation analyses were used to assess time trends. Mortality was
      assessed in univariable and risk-adjusted conditional logistic regression
      analyses with stratification for year of surgery. RESULTS: A total of 1487
      oesophageal, 4404 gastric, 2668 pancreatic and 9743 rectal cancer patients were
      identified. For all cancer entities, significant treatment centralisation was
      observed over the time period (all p <0.001). The rate of mortality was inversely
      related to the annual number of patients treated at a certain hospital. The
      decrease of postoperative mortality from low-volume to high-volume hospitals was
      6.3% to 3.3% for oesophageal cancer (p = 0.019), 4.9% to 3.3% for gastric cancer
      (p = 0.023), 5.4% to 2.0% for pancreatic cancer (p = 0.037), and 2.4% to 1.6% for
      rectal cancer (p = 0.008). These results were confirmed in risk-adjusted analyses
      with a decreased odds of pos-operative death by 49% for oesophageal (odds ratio
      [OR] 0.51, 95% confidence interval [CI] 0.22-1.18; p = 0.085), 32% for gastric
      (OR 0.68, 95% CI 0.48-0.98; p = 0.032), 68% for pancreatic (OR 0.32, 95% CI 0.11
      0.89; p = 0.011) and 29% for rectal cancer (OR 0.71, 95% CI 0.52-0.98; p =
      0.033). CONCLUSION: This population-based analysis - the first of its kind in the
      literature - demonstrates a higher postoperative mortality in low-volume
      hospitals for patients undergoing oesophageal, gastric, pancreatic and rectal
      cancer resection in Switzerland. Hence, such operations should preferably be
      performed in high-volume hospitals.

PMID- 28750419
TI  - Pipamperone and delirium: a preliminary evaluation of its effectiveness in the
      management of delirium and its subtypes.
AB  - INTRODUCTION: Delirium has been recognised as an underdiagnosed and undermanaged
      syndrome with substantial prevalence rates and potentially deleterious
      consequences in the medically ill population. Despite its frequent administration
      in the management of delirium, the effectiveness of pipamperone has not yet been
      evaluated. METHODS: In this retrospective, descriptive cohort study of 192
      patients, pipamperone as monotherapy and as an adjunct to haloperidol,
      haloperidol alone, or atypical antipsychotics were compared with respect to their
      effectiveness in the management of delirium and its subtypes over the course of
      20 days. RESULTS: In this elderly patient population, pipamperone alone and as an
      adjunct to haloperidol was as effective as haloperidol or atypical antipsychotics
      in the management of delirium. Management with low-dose pipamperone monotherapy
      achieved delirium resolution in 70% of patients, over a mean of 6.4 (2-20) days.
      With pipamperone as an adjunct to haloperidol, delirium resolved in 59% of
      patients, over a mean of 7.4 (2-20) days. When haloperidol or atypical
      antipsychotics (risperidone, olanzapine or quetiapine) were used, the delirium
      resolution rates were 72 and 67%, over a mean of 5.2 (2-11) and 6.4 (2-20) days,
      respectively. The addition of pipamperone to haloperidol decreased the
      requirement for lorazepam. Pipamperone proved to be equally effective in all
      delirium subtypes - hypoactive, hyperactive and mixed. Nonetheless, potential
      bias could not be excluded in this observational design. CONCLUSION: From these
      initial results, low-dose pipamperone was as effective as haloperidol or atypical
      antipsychotics in the management of delirium and its subtypes, and was
      benzodiazepine-sparing when used as an adjunct to haloperidol.

PMID- 28750420
TI  - A 10-year observational study of Streptococcus dysgalactiae bacteraemia in
      adults: frequent occurrence among female intravenous drug users.
AB  - Beta-haemolytic streptococci of groups C and G have become increasingly
      recognized as causes of invasive human infections. We reviewed clinical and
      molecular characteristics of Streptococcus dysgalactiae isolates that caused
      bacteraemia in adults from 2006 to 2015. Among 67 episodes, skin and soft-tissue
      infections (43%) and emm types stG62647.0 (26%) were the most frequent clinical
      manifestation and emm type, respectively. Nineteen (28%) episodes occurred in
      intravenous drug users (75% women). Our observational study shows similarities to
      but also differences from other reports. The former include the most frequent
      clinical presentations, and the most frequently found emm types. This report
      highlights a relatively high proportion of female intravenous drug users among S.
      dysgalactiae bacteraemia episodes.

PMID- 28750421
TI  - Outcomes of an Early Protocol for Dependent Conditioning in Lower Extremity
      Microsurgical Free Flaps.

PMID- 28750422
TI  - [Atorvastatin therapy under clinical practice conditions - which LDL-C levels are
      achieved in patients at very high cardiovascular risk?]
AB  - Current information on the utilisation of atorvastatin under clinical practice
      conditions is limited. The cross sectional study DISCOVER documented in the
      period from June until December 2014 dose and effects on lipids in ambulatory
      patients at very high cardiovascular risk, who were treated with atorvastatin
      monotherapy (original drug or generics). Of 2625 patients (mean age 66.1 +/- 10.8
      years, 62.1 % males), 47.0 % had coronary heart disease (CHD), 25.1 % type 2
      diabetes mellitus (DM), and 27.9 % CHD plus concomitant DM. Mean treatment
      duration on atorvastatin was 92.6 +/- 109.6 weeks, mean atorvastatin dose at time
      of documentation was 27.9 +/- 15.8 mg/d. Low-density lipoprotein cholesterol (LDL
      C) < 70 mg/dL was achieved by 10.5 % of the total cohort (7.5 % in DM, 9.3 % in
      CHD, and 15.2 % in CHD+DM). In contrast, according to physicians' subjective
      assessment, 62.7 % of patients reached their individual LDL-C target (with small
      differences between groups). In conclusion, the LDL-C target level < 70 mg/dL as
      recommended by current guidelines is achieved only in a minority of atorvastatin
      treated patients at very high cardiovascular risk.

PMID- 28750423
TI  - Effectiveness of a Laboratory Gate-Keeping Strategy to Overcome Inappropriate
      Test Utilization for the Diagnosis of Heparin-Induced Thrombocytopenia.

PMID- 28750424
TI  - Endovascular Stroke Therapy.

PMID- 28750425
TI  - Emerging Therapeutic Strategies in the Treatment of Hemophilia A.

PMID- 28750426
TI  - Risk Stratification for Acute Pulmonary Embolism in Patients with Atrial
      Fibrillation: Role of CHADS2 Score.

PMID- 28750427
TI  - Environmental Risk Factors for Type 1 Diabetes Mellitus Development.
AB  - Background Although environmental factors induce development of type 1 diabetes
      mellitus (T1DM) in genetically susceptible individuals, many of those factors
      have been uncovered. Therefore, the aim of the present study was to analyze
      associations of T1DM with a wide range of environmental factors. Material and
      Methods A case-control study was conducted on 249 diabetic and 255 healthy
      individuals from the Dalmatian region of South Croatia. Data regarding risk
      factors during pregnancy and early life period of the child were evaluated.
      Results History of antihypertensive intake (p=0.04) and frequency of stressful
      life events during pregnancy (p=0.01) were associated with higher risk of T1DM,
      while hypertension was associated with lower risk of T1DM (p=0.01). Maternal
      age<25 years at delivery was associated with a higher risk of T1DM
      (p=0.01).Diabetic patients had a positive family history of T1DM or T2DM
      (p=0.002) more frequently than controls, while history of infectious diseases was
      inversely associated with the risk of T1DM (p=0.03). A higher risk of T1DM was
      significantly associated with earlier introduction of cow's milk (p=0.001),
      higher number of meals consumed per day (p=0.02), higher frequency of
      carbohydrate (p=0.001) and meat (p=0.01) consumption and stressful life events
      during childhood (p=0.02) while earlier introduction of fruit was associated with
      a lower risk of T1DM (p=0.03) Conclusion This case-control study confirmed
      associations of a large number of environmental factors with development of T1DM
      with emphasis on the association of mother's antihypertensive intake during
      pregnancy, which extends our knowledge about environmental factors related with
      development of T1DM.

PMID- 28750428
TI  - Experiences in Sensor-Augmented Pump Therapy in Families with two Children with
      Type 1 diabetes: A Qualitative Study.
AB  - BACKGROUND: Caring for a child with type 1 diabetes is a tremendous challenge for
      a family. The aim of the study was to explore the experiences of transition to
      sensor-augmented pump therapy (SAP) in families with 2 affected children and the
      internal and external conditions which potentially impede or facilitate the
      adjustment process. METHODS: 5 families (9 parents, 8 children and adolescents)
      who used the SAP technology for 6 months were interviewed to describe their
      experiences. The interviews were analysed using thematic content analysis.
      RESULTS: Qualitative analysis of the transcribed interviews revealed that the
      adaptation process to SAP consisted of several phases and differed among
      families. There were benefits as well as hassles of using SAP with regard to
      managing the diabetes, and psychosocial issues: school and peer relations, as
      well as family relations. While parents clearly regarded the improved metabolic
      control and hypoglycaemic safety as the most important benefits of SAP, the
      hassles reported as most important covered a wide range, from technical problems
      of the system to family conflicts. On the whole, families rated the experience of
      using SAP as a positive one, with most recommending SAP to other families as long
      as they were willing to come to terms with the technology and commit to the work
      and time involved. CONCLUSION: Sensor-augmented pump therapy can be extremely
      beneficial and a resource for families who care for more than one child with
      diabetes. During the adaptation process there is a great need of education and
      frequent follow-up e. g., by telemedical support.

PMID- 28750429
TI  - Self-reported Hypoglycaemic Events in 2 430 Patients with Insulin-treated
      Diabetes in the German Sub-population of the HAT Study.
AB  - Data concerning true hypoglycaemic incidence in insulin-treated patients with
      diabetes in real-world clinical practice are lacking in Germany. The aim of this
      analysis was to determine the incidence of hypoglycaemia experienced by the
      German cohort of patients enrolled in the global Hypoglycaemia Assessment Tool
      (HAT) study. This was a non-interventional, 6-month retrospective and 4-week
      prospective study using self-assessment questionnaires and patient diaries
      assessing patients aged >=18 years in Germany, with type 1 diabetes (T1D) (n=811)
      or type 2 diabetes (T2D) (n=1 619) treated with insulin for >12 months. The
      primary endpoint was the percentage of patients experiencing >=1 hypoglycaemic
      event during the prospective observational period (4 weeks after baseline).
      Predictive and continuous factors (such as age, gender, duration of insulin use
      and HbA1c) contributing to hypoglycaemia risk were explored.During the
      prospective period, at least one hypoglycaemic event was reported by 81.3% of
      patients with T1D and 39.7% of patients with T2D, indicating that hypoglycaemia
      is a common acute complication among patients with insulin-treated diabetes.
      Severe hypoglycaemia was reported by 9.1% of patients with T1D and 5.4% of
      patients with T2D. Higher rates of any and severe hypoglycaemia were reported
      prospectively than retrospectively, regardless of diabetes type, indicating that
      patients retrospectively under-report hypoglycaemia. Prospective rates (events
      per patient-year) of any, nocturnal and severe hypoglycaemia were 80.3, 9.9 and
      3.0 for T1D and 15.6, 2.4 and 1.1 for T2D, respectively. Given the potential for
      recall bias in retrospective reporting, this prospective assessment of
      hypoglycaemia appears more reliable than retrospective assessment. Trial number:
      NCT01696266.

PMID- 28750430
TI  - Prevalence and Distribution of Diabetes Mellitus in a Maximum Care Hospital:
      Urgent Need for HbA1c-Screening.
AB  - OBJECTIVE: Diabetes mellitus affects almost one in 10 individuals in Germany. So
      far, little is known about the diabetes prevalence in maximum care hospitals. We
      assessed the diabetes prevalence, proportion of undiagnosed cases, the
      effectiveness of diabetes screening in a university hospital, the consequences
      for hospital stay and acquired complications. RESEARCH DESIGN AND METHODS: Over a
      4 week period we determined HbA1c from 3 733 adult patients which were
      hospitalized at the university hospital of Tuebingen and had an available blood
      sample. Diabetes diagnosis was defined as HbA1c>=6.5% and/or previously
      documented diabetes diagnosis, prediabetes was defined as HbA1c>=5.7% and <6.5%
      without history of previous diabetes. RESULTS: 23.68% of the patients had
      prediabetes and 22.15% had diabetes with a high variation between the specialised
      departments (range 5-43%). The rate of unknown diabetes was 3.7%, the number
      needed to screen was 17 in patients older than 50 years. Patients with diabetes
      had a prolonged hospital stay compared to the mean length of stay for their
      diagnosis related group (diabetes: 1.47+/-0.24 days; no diabetes: -0.18+/-0.13
      days, p=0.0133). The prevalence of hospital acquired complications was higher in
      diabetic patients (diabetes: 197 of 630; no diabetes: 447 of 2 459, p<0.0001).
      CONCLUSIONS: Every fourth patient in the university hospital had diabetes and
      every second had either prediabetes or diabetes. It is also worthwhile to screen
      for unknown diabetes in patients over the age of 50. The high prevalence and
      negative consequences of diabetes require screening and intensified specialized
      diabetes treatment in hospitals.

PMID- 28750431
TI  - Nitric Oxide Plasma Level as a Barometer of Endothelial Dysfunction in Factory
      Workers.
AB  - Objective Nitric oxide (NO) plays a key role in the regulation of vascular tone
      and is known as one of the key markers of endothelial dysfunction. We
      investigated the relationship between NO and risk factors of lifestyle-related
      disease in factory workers. Methods Our study included 877 factory workers
      presenting hypertension, dyslipidemia and type 2 diabetes. Oxidated forms of NO,
      NO2-/NO3- (NOx) plasma concentrations were measured using a colorimetric method.
      Results NOx plasma levels in patients with lifestyle-related disease were
      significantly lower than those in the controls. The brachial-ankle pulse wave
      velocity (baPWV) measured in those patients was significantly greater than that
      of the controls. Multiple regression analysis revealed that LDL cholesterol was
      an independent risk factor for reducing NOx plasma concentrations. Interestingly,
      individuals with low NOx plasma concentrations were more likely to present type 2
      diabetes compared to those with the highest plasma levels of NOx (odds ratio [OR]
      [95% confidence interval; CI]=3.65 [1.61-8.28], P=0.002, 2.67 [1.15-6.20],
      P=0.022, and 3.27 [1.43-7.48], P=0.005). Subjects with the lowest levels of
      plasma NOx were more likely to present dyslipidemia (OR [95% CI]=1.69 [1.13
      2.53], P=0.01). Conclusion Endothelial function evaluated with plasma NOx may be
      indicative of lifestyle-related diseases independently from the vascular function
      assessed using baPWV.

PMID- 28750432
TI  - Hyperthyroidism in Patients with Graves' Ophthalmopathy, and Thyroidal, Skeletal
      and Eye Muscle Specific Type 2 Deiodinase Enzyme Activities.
AB  - Graves' ophthalmopathy is characterized by hyperthyroidism, which is associated
      with higher serum T3 levels than T4 due to deiodinase enzymes.The effect of
      Graves' patient's sera (n=52) with elevated thyroid hormone and TSH receptor or
      thyroid peroxidase antibody (anti-TPO) levels was investigated on thyroidal,
      skeletal and eye muscle type 2 deiodinase enzyme (DII) activities. DII activities
      were measured with 125I-T4 substrate, while thyroid hormone and antibody levels
      with immunoassays.In Graves' ophthalmopathy, sera with elevated FT4 or FT3 levels
      reduced DII activites remarkably in all tissue fractions. Thyroidal DII
      activities were lower than those using eye muscle fraction (0.6+/-0.22 vs 1.14+/
      0.43 pmol/mg/min, P<0.006). Effect of sera with increased FT3 levels demonstrated
      also reduced DII activities in patients with Graves' ophthalmopathy after
      methimazole therapy compared to those who had no ophthalmopathy (2.88+/-2 vs
      20.42+/-11.82 pmol/mg/min, P<0.006 for thyroidal fraction, 4.07+/-2.72 vs 29.22+/
      15.46 pmol/mg/min, P<0.004 for skeletal muscle, 5.3+/-3.47 vs 37.87+/-18.82
      pmol/mg/min, P<0.003 for eye muscle). Hyperthyroid sera with TSH receptor
      antibodies resulted in increased DII activities, while sera with anti-TPO
      antibodies were connected to lower DII activities in Graves' ophthalmopathy.In
      summary, the actions of hyperthyroid sera derived from patients with Graves'
      disease were tested on tissue-specific DII activities. Elevated FT4 level-induced
      DII inactivation is present in Graves' ophthalmopathy, which seems to be also
      present at the beginning of methimazole therapy. Stimulating TSH receptor
      antibiodies increased DII activities via their nongenomic effects using sera of
      hyperthyroid Graves' ophthalmopathy, but anti-TPO antibodies could influence DII
      activities via altering FT4 levels.

PMID- 28750433
TI  - Effect of a 12-Week Aerobic Exercise Training on Serum Fetuin-A and Adipocytokine
      Levels in Type 2 Diabetes.
AB  - OBJECTIVE: We aimed to evaluate the effect of 12-week aerobic exercise training
      on fetuin-A levels in type 2 diabetes mellitus and examine the relationships
      between fetuin-A and adipocytokine levels and cardiovascular risk factors.
      METHODS: The study included 32 patients with type 2 diabetes mellitus who were
      assigned to an exercise or a control group. The exercise group underwent 12 weeks
      of exercise (consisting of a 5-min warm-up, 60-min aerobic bicycle training
      performed at 70% of the maximal heart rate, a cool-down period, 5 times/week).
      Adiponectin, resistin, and fetuin-A serum levels were measured using enzyme
      linked immunosorbent assay. Leptin serum levels were measured by a
      radioimmunoassay. RESULTS: Exercise for 12 weeks significantly reduced serum
      fetuin-A (643.1+/-109.4 to 448.7+/-92.5 MUg/mL, P<0.05), leptin (11.9+/-7.2 to
      8.6+/-5.7 ng/dL, P<0.05), and resistin (3.2+/-1.5 to 2.2+/-1.4 ng/mL, P<0.05)
      levels, but increased adiponectin (6.9+/-1.9 to 8.1+/-1.7 ug/mL, P<0.05) levels.
      In the exercise group, Deltafetuin-A positively correlated with differences in
      weight (r=0.654, P=0.046), body mass index (r=0.725, P=0.002), waist
      circumference (r=0.898, P=0.013), and adiponectin levels (r=0.662, P=0.035).
      CONCLUSIONS: Aerobic exercise significantly decreased serum fetuin-A levels in
      type 2 diabetes mellitus, which can be attributed to weight loss and related to
      increased adiponectin levels.

PMID- 28750434
TI  - [26 Years of the Erlangen Glaucoma Registry: Demographic and Perimetric
      Characteristics of Patients Through the Ages].
AB  - Background The history of the Erlangen Glaucoma Registry goes back 26 years. In
      this study, we present retrospective demographic and perimetric data on the
      initial visit of patients with ocular hypertension (OHT), pre-perimetric
      (prePOAG) and perimetric primary open-angle glaucoma (POAG), normal tension
      glaucoma (NTG) and secondary open-angle glaucoma (SOAG) and correlate these
      results with the latest perimetric data. Material and Methods 1406 (754 patients)
      of the Erlangen Glaucoma Registry (EGR; NTC00494923) were investigated
      retrospectively between 1991 and 2016 covering: demographic data (age, visual
      acuity, intraocular pressure [IOP]), diagnosis and perimetric characteristics
      (mean defect [MD], loss variance [LV]) at the initial visit and the latest
      perimetric data. Results (1) 558 eyes of OHT, 347 prePOWG, 236 POAG, 161 NTG and
      104 SOWG were recruited in the Erlangen Glaucoma Registry between 1991 and 2007.
      (2) The initial age was significantly lower for OHT (43.79 +/- 13.64) than for
      perimetric open-angle glaucoma (NTG: 54.46 +/- 11.41, p < 0.001; POAG: 54.00 +/-
      11.27, p < 0.001; SOAG: 47.92 +/- 12.37, p = 0.008). Patients with prePOAG (48.62
      +/- 11.98) were significantly younger than patients with POAG/SOAG (p < 0.001).
      (3) The best corrected visual acuity was better for OHT (1.04 +/- 0.14, p <
      0.001) and prePOAG (1.05 +/- 0.15, p < 0.001) than for POAG (0.95 +/- 0.16), SOAG
      (0.93 +/- 0.23) and NTG (0.93 +/- 0.18). (4) Initial IOP was significantly higher
      for OHT (19.08 +/- 2.25 mmHg), prePOAG (19.18 +/- 3.90 mmHg), POAG (18.29 +/-
      4.11 mmHg) and SOAG (18.57 +/- 5.34 mmHg) than for NTG (15.23 +/- 2.83 mmHg, p <
      0.001). (5) Since 1991, increasing numbers of patients with POAG and SOAG were
      seen at the initial visit. (6) Trend for MD and LV between 1991 and 2016: a trend
      for increasing MD at the initial visit was detected for prePOAG and POAG, yet
      OHT, NTG and SOAG showed a decreasing trend for MD at the initial visit. All
      patient groups showed perimetric progression. Conclusion Since its start in 1991,
      the patients of the Erlangen Glaucoma Registry exhibited perimetric progression
      up to the year 2016, although antiglaucomatous therapy was re-evaluated and
      optimised if target IOP was not achieved.

PMID- 28750435
TI  - [Cell Transplantation in Age-related Macular Degeneration].
AB  - Robert Machemer offers a surgical approach to age-related macular degeneration
      with his retinal rotation. There is already considerable experimental and
      clinical knowledge available in Europe and the US on transplantation techniques
      for age-related macular degeneration. On average, initial visual acuity can be
      preserved. When photodynamic therapy was standard for exudative AMD,
      transplantation was superior. Photodynamic therapy could not stop, but was
      instead able to slow down visual loss. Currently, VEGF-blocker therapy has
      priority, because the visual acuity can be improved. However, this advantage does
      not last much longer than two years. Therefore, in the future, transplantation
      with new cells and less surgical risk may be reconsidered. At present, homologous
      RPE stem cells show promising results. They may be delivered as "sheets" or as
      single cells. For dry AMD only, a prophylactic approach seems reasonable,
      because, thus far, we are unable to reverse the atrophy on the retinal side.

PMID- 28750436
TI  - [Retinal Vascular Occlusion: Modern Therapeutic Approaches].
AB  - Retinal artery occlusion (RAO) should be evaluated as an emergency and can be
      seen as an ocular analogue to the cerebral apoplex. Both have the same
      arteriosclerotic risk factors, which are also responsible for cardiac,
      circulatory and cerebrovascular diseases. That is why an intensive
      interdisciplinary clarification is necessary to recognize possible comorbidities
      in time and, if necessary, to treat them. The current therapeutic possibilities
      of an acute RAO are very limited in their efficiency regarding visual
      improvement. Methods for systemic lysis cannot be recommended in routine care
      because of their significantly increased side-effect profile. However, there is a
      limited window of time of up to 6 hours after the onset of symptoms in which an
      intervention appears to be useful at all. On the other hand, the new therapeutic
      possibilities of retinal vein occlusions (RVO) led to marked visual improvements,
      especially due to the intravitreal application of anti-VEGF. Safety and
      efficiency of the individual anti-VEGF drugs are comparable according to clinical
      trials. Alternatively, the use of intravitreal steroids can be considered,
      whereby the side-effect profile should be carefully weighed. In the presence of
      retinal ischaemia, peripheral laser coagulation can have a stabilizing effect on
      visual acuity and prevents neovascularization. It is postulated that the
      combination of anti-VEGF and laser therapy might have a symbiotic effect.

PMID- 28750437
TI  - ?

PMID- 28750438
TI  - ?

PMID- 28750439
TI  - ?

PMID- 28750440
TI  - ?

PMID- 28750441
TI  - ?

PMID- 28750442
TI  - ?

PMID- 28750443
TI  - ?

PMID- 28750444
TI  - ?

PMID- 28750445
TI  - ?

PMID- 28750446
TI  - [Modern endoscopic imaging tools for urothelial carcinoma of the urinary
      bladder].
AB  - Cystoscopy is the gold standard for the initial diagnosis of urothelial carcinoma
      in the urinary bladder (UCB). White light exhibits significant limitations in its
      ability to detect flat lesions or carcinoma in situ. Photodynamic Diagnosis (PDD)
      and Narrow Band Imaging (NBI) are established techniques which may improve the
      detection rates of UCB and reduce the risk of recurrence. Multiple novel tools
      have been developed in order to improve the diagnostic accuracy of endoscopic
      procedures, including Digital Contrast Enhancement Technology, Confocal Laser
      Endomicroscopy (CLE) and Optical Coherence Tomography (OCT). In future, spectral
      analysis of urothelial lesions may be achieved by Raman spectroscopy, thus
      providing information about biological alterations in the tissue. Furthermore,
      molecular imaging may allow specific targeting by fluorescent antibodies or small
      molecule agents, thus enabling differential diagnosis of suspicious lesions.
      Software-based approaches have been developed to incorporate computer-aided
      diagnosis and improve digital documentation of endoscopic findings. This study
      reviews current and future developments in the field of modern endoscopy of the
      urinary bladder and discusses the different approaches.

PMID- 28750447
TI  - [En-bloc resection of bladder tumours (ERBT): current and future perspectives].
AB  - Limitations inherent in the conventional transurethral resection of bladder
      tumours, the standard approach for diagnosis and treatment of bladder cancer, are
      well known: staging errors due to insufficient resection depth as well as
      intravesical tumour fragmentation, both of which make histopathological
      evaluation difficult. The purpose of this review is to present recent clinical
      data on the en-bloc resection of bladder tumours (ERBT), which has been
      demonstrated to offer a high potential to overcome these limitations. The recent
      findings show that ERBT provides a good resection quality with varying detection
      rates for tunica muscularis, which is a surrogate marker for resection quality
      regarding muscle-invasive tumours. ERBT can be performed using all energy
      sources. Available data show no relevant difference with regard to perioperative
      morbidity compared with cTURB. No conclusions can be drawn regarding the impact
      of ERBT on recurrence as the data are partly controversial. This has to be
      defined by further studies.

PMID- 28750448
TI  - [Role of the human ErbB family receptors in urothelial carcinoma of the bladder:
      mRNA expression status and prognostic relevance].
AB  - Background Altered expression of epidermal growth factor (EGF) family (ErbB)
      receptors in urothelial carcinoma of the urinary bladder (UCB) has been
      associated with adverse outcomes. Given the limited treatment options in UCB,
      EGFR and HER2 (ERBB2) represent established therapeutic targets in other
      entities. We assessed the expression of ErbB family receptors (ERBB1 - 4) on mRNA
      levels in correlation with histopathological and clinical parameters in patients
      treated with radical cystectomy (RC). Methods 94 patients (female = 22; male =
      72; median age: 66.5 years [range 39 - 88]) with UCB (pT1 - 4) treated with RC
      were included. Median follow-up was 28.2 months (range 0.6 - 139). ErbB mRNA
      expression levels were determined after extraction from formalin-fixed, paraffin
      embedded tissue. Univariate and multivariate Cox proportional hazard models were
      performed to assess recurrence-free survival (RFS) and cancer-specific survival
      (CSS). Results Overexpression was observed in 18 % (ERBB3), 39 % (EGFR), 34 %
      (HER2, ERBB2) and 30 % (ERBB4) of patients, respectively. Higher pathological
      stage (p = 0.012), a positive nodal status (p = 0.0002), high ERBB4 (p = 0.012)
      and high HER2 (ERBB2) levels (p = 0.014) were significantly associated with
      reduced RFS. A negative lymph node status (p = 0.0003) and low HER2 (ERBB2) (p =
      0.042) levels had a favourable prognostic impact on CSS. In multivariate
      analysis, positive pN stage (p = 0.0011) and high ERBB4 (p = 0.0073) expression
      were independent predictors of reduced RFS. Higher pN stage (p = 0.0016) was an
      independent predictor of reduced CSS. Conclusions Higher HER2 (ERBB2) expression
      is associated with an unfavourable prognosis in patients with UCB. However, it is
      not an independent predictor when measured on mRNA levels. Further analyses need
      to clarify which patients may still benefit from HER2 (ERBB2) targeted drugs.

PMID- 28750449
TI  - ?

PMID- 28750450
TI  - Primary Amelanotic CNS Melanoma: Case Report and Literature Review.
AB  - Primary malignant melanomas of the central nervous system (CNS) are rarely seen
      entities in the clinical routine. Primary amelanotic melanomas are even rarer. In
      our literature review, we found only six case reports of primary amelanotic CNS
      melanomas. Our case report describes the course of a 71-year-old man with a
      primary amelanotic CNS melanoma with secondary spread to the spine.

PMID- 28750451
TI  - Long-term Clinical Outcomes and Quality of Life in Elderly Patients Treated with
      Interspinous Devices for Lumbar Spinal Stenosis.
AB  - BACKGROUND AND OBJECTIVE:  Lumbar spinal stenosis (LSS) is a common degenerative
      condition that occurs in the spine with increasing age. Clinically, LSS causes a
      progressive reduction in walking autonomy, resulting in a poor quality of life
      and impaired functional capacity. The aim of this study was to evaluate the
      clinical outcome and quality of life of elderly patients presenting with LSS and
      associated comorbidities after a 5-year follow-up who were treated with an
      interspinous process device (IPD). MATERIAL AND METHODS:  Sixty patients > 75
      years of age presenting with symptomatic degenerative LSS were included. All were
      treated with an IPD under local anesthesia. American Society of Anesthesiology
      score, Zurich Claudication Questionnaire, and Short Form 36 were evaluated pre-
      and postoperatively and at the follow-up visit each year for 5 years. RESULTS: 
      The mean surgery time while under local anesthesia was 20 minutes. Forty-eight
      patients were followed for 5 years. Significant clinical improvements in all
      outcome scores (p < 0.05) both postoperatively or at follow-up were found.
      CONCLUSIONS:  IPD seems to be an effective and safe treatment for LSS in elderly
      patients with general comorbidities. In our study, all followed up patients had a
      meaningful improvement of their quality of life even at 5 years after surgery.

PMID- 28750452
TI  - Mathematical Equation for Precise Burr Hole Placement in Stereotactic Deep Brain
      Stimulation Lead Placement.

PMID- 28750453
TI  - Overexpression of MicroRNA-106b-5p Attenuates Kidney Injuries after Deep
      Hypothermic Circulatory Arrest in Rats.
AB  - BACKGROUND: MicroRNAs (miRNA) have been identified to exert a wide range of
      biological functions in acute kidney injury (AKI) after deep hypothermic
      circulatory arrest (DHCA). We sought to investigate the renoprotection of miRNA
      106b-5p in a rat model of DHCA by targeting phosphatase and tensin homolog
      (PTEN). METHODS: Overexpression of miRNA-106b-5p in vivo was conducted by
      directly injection of lentivirus vectors containing pre-miRNA-106b-5p into the
      renal parenchyma of the animals under the ultrasound guidance 7 days before DHCA.
      The vehicle or control lentivirus vectors were given to the control group or the
      control vector group, respectively. Renal function and apoptosis activity were
      evaluated by serum cystatin C, serum/tissue neutrophil gelatinase-associated
      lipocalin (NGAL), and terminal deoxynucleotidyl transferase dUTP nick-end
      labeling assay (TUNEL) at 24 hours after surgery. Expressions of miRNA-106b-5p,
      PTEN, and caspase-3 in the kidney were evaluated by quantitative real-time
      polymerase chain reaction and western blot analysis. RESULTS: Transfection of pre
      miRNA-106b-5p significantly enhanced the expression of miRNA-106b-5p and
      dramatically downregulated the expressions of PTEN in the kidney compared with
      the control group. Renal functions were markedly protected by pretreatment with
      pre-miRNA-106b-5p as evidenced by decreases in serum cystatin C and serum/tissue
      neutrophil gelatinase-associated lipocalin at 24 hours after surgery. The pre
      miRNA-106b-5p group showed significantly fewer apoptotic cells and lower levels
      of caspase-3 activation than the control group. CONCLUSIONS: Overexpression of
      miRNA-106b-5p attenuates kidney injuries after DHCA, possibly by inhibition of
      PTEN.

PMID- 28750454
TI  - Minimally Invasive Mitral Valve Surgery for Mitral Valve Infective Endocarditis.
AB  - BACKGROUND: The feasibility of minimally invasive mitral valve (MV) surgery in
      infective endocarditis (IE) has not been reported in detail. We assessed the
      safety, efficacy, and durability of the minimally invasive approach through a
      right anterolateral minithoracotomy for surgical treatment of MV IE. METHODS: A
      review of the Leipzig Heart Center database revealed 92 eligible patients
      operated on between 2002 and 2013. All patients had undergone minimally invasive
      surgery for IE. The indication for surgery was isolated IE of the MV in all
      patients. Baseline and intraoperative data, as well as clinical outcomes and
      short-term follow-up were analyzed retrospectively. RESULTS: The patients' mean
      age was 60.9 +/-  15.3 years, the logistic EuroSCORE II was 19.6 +/- 19.1%, and
      64.1% (59) were male. MV repair was feasible in 23.9% (22/92) of patients. Repair
      techniques included annuloplasty ring implantation, anterior mitral leaflet
      resection, posterior mitral leaflet resection, and implantation of neochordae. MV
      replacement was performed in 69 patients (75%), a mitral annulus patch in 1
      patient, and concomitant tricuspid valve surgery for tricuspid regurgitation in 5
      patients. Bacteriological analysis showed staphylococcus infection in 45.5%,
      streptococcus in 36.4%, enterococcus in 13.6%, and others in 4.5%. The 30-day
      mortality rate was 9.8% (9 patients). The 1-year follow-up showed a 1-year
      survival rate of 77.7 +/- 4.4% and freedom from reoperation within 1 year due to
      reendocarditis of 93.3 +/- 2.1%. CONCLUSIONS: The minimally invasive approach is
      suitable for the treatment of IE of the MV. It is a good technique in IE in
      selected patients.

PMID- 28750455
TI  - Sarcoidosis: Evolving Concepts.

PMID- 28750456
TI  - Sarcoidosis around the Globe.

PMID- 28750457
TI  - Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights.

PMID- 28750458
TI  - Imaging for Sarcoidosis.

PMID- 28750459
TI  - Pulmonary Sarcoidosis.

PMID- 28750460
TI  - Sarcoidosis-Associated Pulmonary Hypertension.

PMID- 28750461
TI  - Lofgren's Syndrome: Diagnosis, Management, and Disease Pathogenesis.

PMID- 28750462
TI  - Cardiac Involvement in Sarcoidosis: Evolving Concepts in Diagnosis and Treatment.

PMID- 28750463
TI  - Neurosarcoidosis.

PMID- 28750464
TI  - Ocular Involvement in Sarcoidosis.

PMID- 28750465
TI  - Current Medical Therapy for Sarcoidosis.

PMID- 28750466
TI  - Sarcoidosis: Drugs under Investigation.

PMID- 28750467
TI  - Solid Organ Transplantation in Sarcoidosis.

PMID- 28750468
TI  - Quality of Life in Sarcoidosis.

PMID- 28750469
TI  - Maternal Gut Microbiome Biodiversity in Pregnancy.
AB  - OBJECTIVE: To measure maternal gut microbiome biodiversity in pregnancy.
      MATERIALS AND METHODS: In phase 1, maternal fecal samples were collected by
      rectal swab in 20 healthy pregnant women (14-28 weeks gestation) to measure
      bacterial abundance. In phase 2, fecal samples were collected from 31 women at
      enrollment (<20 weeks gestation, baseline) and at 36 to 39 weeks of gestation
      (follow-up). We assessed cluster analysis to assess bacterial community profiles
      at the phylum level longitudinally through pregnancy. DNA was extracted from
      swabs, followed by PCR of the bacterial 16s rRNA gene and multiplex high
      throughput sequencing (Ion Torrent). RESULTS: In phase 1, 16 of 20 samples
      yielded usable data. White women (n = 10) had greater abundance of Firmicutes (23
      +/- 0.15 vs. 16% +/- 0.75, p = 0.007) and Bacteroidetes (24 +/- 0.14 vs. 19% +/-
      0.68, p = 0.015) compared with non-White women (n = 6). In the 11 paired
      specimens, Bacteroidetes increased in abundance from baseline to follow-up.
      Compared with women who gained weight below the median gestational weight gain
      (GWG, <15.4 kg), those who gained above the median GWG had increased abundance of
      Bacteroidetes (p = 0.02) and other phyla (p = 0.04). CONCLUSION: Maternal
      microbiome biodiversity changes as pregnancy progresses and correlates with GWG.

PMID- 28750470
TI  - Clot waveform analysis using CS-2000iTM distinguishes between very low and absent
      levels of factor VIII activity in patients with severe haemophilia A.
AB  - INTRODUCTION: A recently developed method to assess comprehensive coagulation
      function, clot waveform analysis (CWA), accurately detect low levels (<1 IU/dL)
      of factor VIII activity (FVIII:C) in haemophilia A patients (HA-pts).
      Improvements are needed, however, to differentiate patients with very low from
      absent levels of FVIII:C. AIM: We attempted to optimize CWA using the coagulation
      analyser CS-2000iTM to distinguish between very low levels and absent FVIII:C in
      severe HA-pts. METHODS AND RESULTS: Activated partial thrombin time (aPTT)-based
      clot waveforms were determined in FVIII-deficient plasmas mixed with various
      amounts of recombinant FVIII. Clot times (CT) were shortened, and maximum
      coagulation velocity (|min1|) and acceleration (|min2|) were increased in FVIII
      dose-dependently at levels ranging from 0.25 to 100 IU/dL. The lowest level of
      FVIII:C detected was 0.25 IU/dL. Plasma samples from modestly severe (MS-HA; 0.5
      <1.0 IU/dL), very severe (VS-HA; 0.25-<0.5 IU/dL), extremely severe (ES-HA; <0.25
      IU/dL) and inhibitor-positive HA-pts (HA-inh) were examined. The CT was markedly
      prolonged in all instances but showed significant differences between the
      different groups insufficiently. The |min1| and |min2| in HA-inh were lower
      compared to the other groups (P<.05). A new parameter (slope-|min1|) reflecting
      average coagulation acceleration was derived. This index (median) was lower in HA
      inh (0.0042) compared to ES-HA (0.0068) and VS-HA (0.011) with greater
      significant differences (P<.01), and an index of <.005 reflected the total
      absence of FVIII in the presence of inhibitor. CONCLUSION: The slope-|min1|
      parameter could provide a useful index for evaluating very low and absent levels
      of FVIII and/or the development of FVIII inhibitor in HA-pts.

PMID- 28750471
TI  - Modulation of the activated protein C pathway in severe haemophilia A patients:
      The effects of thrombomodulin and a factor V-stabilizing fab.
AB  - INTRODUCTION: The thrombomodulin (TM)/activated protein C (APC) system is a key
      regulator of haemostasis, limiting amplification and propagation of the formed
      blood clot to the injury site. Dampening APC's inhibition of factor V (FV) and
      factor VIII (FVIII) may be a future strategy in developing next-generation
      therapeutic targets for haemophilia treatment. AIMS: To determine ex vivo the
      respective concentration-dependent effects of TM and a FV-stabilizing Fab on the
      APC regulatory pathway in severe FVIII-deficient blood and plasma. METHODS: Ten
      severe haemophilia A subjects and one healthy control were enrolled. Blood was
      spiked with TM (0, 1, 2.5, 5, 10, 20.0 nmol/L) and FV-stabilizing Fab (0, 3, 15,
      65, 300 nmol/L). The respective effects were compared to FVIII concentrations of
      3- and 10% using rotational thromboelastometry clotting time (CT) and thrombin
      generation analysis (TGA). RESULTS: With 1 and 2.5 nmol/L TM, 5% FVIII resulted
      in CT similar to the absence of TM, suggesting it completely reversed the effect
      of APC. Increasing TM concentrations also reduced peak thrombin generation and
      ETP. The addition of 300 nmol/L FV-stabilizing Fab returned CT to nearly
      baseline, but for most subjects was less than the effects of 3- or 10% FVIII. The
      FV-stabilizing Fab produced similar or greater thrombin generation compared to
      samples with 3- or 10% FVIII. CONCLUSIONS: The FV-stabilizing Fab resulted in
      enhanced CT and TGA parameters consistent with FVIII levels of 3- and 10%.
      Additional studies need to further characterize how modulating the APC pathway
      may prove beneficial in developing new haemophilia drug targets.

PMID- 28750472
TI  - Identifying bleeding: Go with the flow.

PMID- 28750473
TI  - A de novo factor VIII mutation in a haemophilia B family leading to combined
      deficiency of factor VIII and IX.

PMID- 28750474
TI  - Potential misdiagnosis of von Willebrand disease and haemophilia caused by
      ineffective mixing of thawed plasma.
AB  - INTRODUCTION: von Willebrand disease (VWD) reflects a loss or dysfunction in von
      Willebrand factor (VWF), while haemophilia represents a loss or dysfunction of
      clotting factors such as factor VIII (FVIII) or FIX. Their diagnosis requires
      laboratory testing, with this potentially compromised by preanalytical events,
      including poor sample quality. This study assessed the effect of inadequate
      mixing as a potential cause of VWD and haemophilia misdiagnosis. METHODS: After
      completion of requested testing, 48 consecutive patient samples comprising
      separate aliquots from single collections were individually pooled, appropriately
      mixed, then frozen in separate aliquots, either at -20 degrees C or -80 degrees C
      for 2-7 days. Each sample set was then thawed and the separate aliquots subjected
      to separate mixing protocols (several inversions, blood roller, vortex) vs a non
      mix sample, and all aliquots then tested for various VWF and factor assays.
      RESULTS: Non-mixing led to substantial reduction in VWF and factors in about 25%
      of samples, that in some cases could lead to misdiagnosis of VWD or haemophilia.
      Interestingly, there were also some differences observed with respect to
      different mixing protocols. CONCLUSIONS: Our study identified ineffective or
      variable mixing of thawed plasma samples as potential causes of misdiagnosis of
      VWD or haemophilia. Further education regarding the importance of appropriate
      mixing appears warranted.

PMID- 28750476
TI  - Haematuria work-up in general care-A German observational study.
AB  - BACKGROUND: Haematuria is a common finding in the population and the diagnostic
      workflow of this symptom represents a large proportion of "work-load" in the
      urological outpatient clinic. AIMS: The intention of this study was to verify if
      the intensive diagnostic procedures of haematuria patients is justified by
      detection of a significant proportion of genito-urinary tract cancers. MATERIALS
      AND METHODS: In a retrospective design 1049 consecutive patients, who presented
      themselves with macro- or microhaematuria in the outpatient clinic PURR in the
      time from 2011 to 2012, were included in the study and the diagnostic procedures
      including ultrasound, intravenous urography, computed tomography of the abdomen
      and urethrocystoscopy as well as therapeutic consequences with its results were
      analysed. RESULTS: The study group comprised 570 women (54.3%) and 479 men
      (45.7%) with a median age of 58 years and macrohaematuria occurred in 89
      patients. Diagnostics revealed seven patients with renal cell cancer, six
      patients with urothelial cell cancer of the renal pelvis, four patients with
      urothelial cell cancer of the ureter, 65 patients with urothelial cell cancer of
      the lower urinary tract and 17 patients with prostate cancer. Age, male gender
      and macrohaematuria were associated with a higher risk of cancer. CONCLUSIONS:
      The high incidence of urinary tract cancer in the data presented here support the
      rationale for diagnostic work-up of patients with micro- or macrohaematuria.
      Prospective randomised trials are necessary to identify index patients for second
      work-up after a primarily negative investigation as well as the role of molecular
      markers, which possibly enable to omit invasive work-up.

PMID- 28750475
TI  - Inpatient glucose management programme in the Asian healthcare setting.
AB  - AIM: To implement an inpatient glucose management (IGM) programme in the general
      medical wards and evaluate its clinical efficacy. METHOD: Consecutive patients
      admitted to selected medical wards over a 12-month period were included in the
      IGM programme. All patients with >=3 capillary blood glucose (CBG) readings
      (>10.0 mmol/L and/or <4.0 mmol/L) over a 24-hour period were identified
      electronically. A multidisciplinary team of diabetes care providers would provide
      specialist input to these patients. The control group comprised of consecutive
      patients admitted over the preceding 12 months. Outcome glucose measures include
      mean in-hospital glucose (MHG), mean patient-day glucose (MDG), proportion of CBG
      readings at predefined cut-offs and length of stay (LOS). RESULTS: Both the MHG
      and MDG were significantly lower following intervention (10.0+/-2.4 mmol/L vs
      11.2+/-2.6 mmol/L, P<.001; 10.0+/-2.3 mmol/L vs 11.2+/-2.6 mmol/L, P<.001,
      respectively). Prevalence of hyperglycaemic events, defined by CBG >10.0 mmol/L,
      was significantly lower at 36.5% versus 51.6% (P<.001). Hypoglycaemic events of
      CBG <4.0 mmol/L remained infrequent at <1.0% before and after IGM programme. A
      greater proportion of glucose readings was controlled within the target range of
      4.0-10.0 mmol/L (62.6% vs 47.6%, P<.001). With the IGM programme in place, more
      patients received scheduled CBG monitoring, and a significant shortening of mean
      LOS by 3.2 days was observed (P=.02). CONCLUSIONS: The IGM programme was
      effective in improving inpatient glycaemic monitoring and control in the general
      medical wards, with a significant reduction in LOS observed. These demonstrated
      the programme's potential to enhance quality and efficiency of patient care.

PMID- 28750477
TI  - Anti-PCSK9 antibodies for hypercholesterolaemia: Overview of clinical data and
      implications for primary care.
AB  - OBJECTIVES: To put data from our recent systematic review of phase 3 studies of
      anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies into the
      context of clinical practice. METHODS: Data from studies previously identified by
      a systematic review of phase 3 studies of alirocumab and evolocumab and
      additional references from non-systematic literature searches were used. We
      evaluated the hypothetical cardiovascular (CV) benefit in cases of typical
      patients in whom anti-PCSK9 antibodies may be recommended, using preliminary
      major CV event (CVE) rates from long-term clinical trials of anti-PCSK9
      antibodies and from extrapolations derived from correlation between low-density
      lipoprotein cholesterol (LDL-C) reduction and CV benefit with other lipid
      lowering therapies (LLTs). RESULTS: Rapid (within 1-2 weeks) and persistent (8-74
      weeks) reductions in LDL-C levels were achieved with anti-PCSK9 antibodies. When
      combined with statins (+/- ezetimibe), high rates of LDL-C goal achievement were
      observed (41%-87% with alirocumab and 63%-100% with evolocumab). In long-term
      alirocumab and evolocumab studies, reductions in major CVEs of 48% and 53%,
      respectively, were observed. For every 38.7 mg/dL (1 mmol/L) reduction in LDL-C,
      a 22% reduction in relative CVE risk is predicted. Applying these assumptions to
      typical patients who have high-very high risk (15%-60% absolute 10-year CVE risk)
      and elevated LDL-C despite maximally tolerated statins, the 10-year number needed
      to treat with an anti-PCSK9 antibody to prevent one additional CVE varies from 4
      to 26, depending on baseline LDL-C levels and residual absolute CVE risk.
      CONCLUSIONS: Anti-PCSK9 antibodies effectively lower LDL-C levels in a broad
      patient population. While awaiting comprehensive data from CV outcome trials,
      these agents should be considered in very high risk patients, such as those in
      secondary prevention and those with familial hypercholesterolaemia who are
      already receiving maximally tolerated LLTs, have not achieved their LDL-C goal
      and require substantial reductions in LDL-C.

PMID- 28750478
TI  - Multiple DSM-5 substance use disorders: A national study of US adults.
AB  - OBJECTIVE: Our aim is to determine the lifetime and past-year prevalence
      estimates of multiple Diagnostic and Statistical Manual of Mental Disorders fifth
      edition (DSM-5) substance use disorders (SUDs) among U.S. adults. METHODS: The
      2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions
      featured in-person interviews with a nationally representative sample of adults
      aged 18 and older. RESULTS: The majority of past-year nonalcohol DSM-5 SUDs had
      at least 1 other co-occurring past-year SUD, ranging from 56.8% (SE = 3.4) for
      past-year prescription opioid use disorder to 97.5% (SE = 2.7) for past-year
      hallucinogen use disorder. In contrast, only 15.0% (SE = 0.6) of past-year
      alcohol use disorders had a co-occurring past-year SUD. The odds of past-year
      multiple SUDs were greater among males, younger adults, African-Americans, and
      those with mood, personality, posttraumatic stress, or multiple psychiatric
      disorders. CONCLUSIONS: Assessment, diagnosis, and treatment often focus on
      individual substance-specific SUDs rather than multiple SUDs, despite evidence
      for substantial rates of polysubstance use in clinical and epidemiological
      studies. There are notable differences in the prevalence of multiple SUDs between
      alcohol use disorders and other nonalcohol SUDs that have important clinical
      implications; for example, multiple SUDs are more persistent than individual
      SUDs. These findings suggest that clinical assessment and diagnosis should screen
      for multiple SUDs, especially among adults with nonalcohol DSM-5 SUDs.

PMID- 28750479
TI  - The impact of alcohol hangover symptoms on cognitive and physical functioning,
      and mood.
AB  - Hangover research often records the presence and severity of symptoms experienced
      the day after heavy alcohol consumption. However, usually no information is
      gathered on the impact of experiencing these symptoms on mood, cognition, and
      physical activities. An online survey was held among Dutch students, aged 18-30
      years, who recently had a hangover. Overall hangover severity (i.e., a single 1
      item rating) and the severity of 22 individual symptoms were rated on an 11-point
      scale ranging from 0 (absent) to 10 (extreme). In addition, for each symptom,
      participants were asked to rate their respective negative impact on (a) cognitive
      functioning, (b) physical functioning, and (c) mood, on a 6-point Likert scale
      ranging from 0 (no impact) to 5 (extreme). N = 1837 subjects completed the
      survey. The mean (SD) overall (1-item) hangover severity score was 6.1 (1.9).
      Sleepiness, being tired, thirst, and concentration problems were the most
      frequently reported hangover symptoms. These symptoms also reached the highest
      severity scores (ranging from 6.3 to 7.0). The 4 symptoms with the biggest
      combined impact on mood, and cognitive and physical functioning were being tired,
      sleepiness, headache, and concentration problems. In conclusion, whereas severity
      and impact scores usually correspond well, some frequently reported symptoms with
      moderate to high severity scores had little impact on mood, and cognitive and
      physical functioning (i.e., reduced appetite, regret, and thirst).

PMID- 28750480
TI  - Development of an inhibitor in a man with mild haemophilia A.

PMID- 28750482
TI  - Infrared ion spectroscopy inside a mass-selective cryogenic 2D linear ion trap.
AB  - We demonstrate operation of the first cryogenic 2D linear ion trap (LIT) with
      mass-selective capabilities. This trap presents a number of advantages for
      infrared ion "action" spectroscopy studies, particularly those employing the
      "tagging/messenger" spectroscopy approach. The high trapping efficiencies,
      trapping capacities, and low detection limits make 2D LITs a highly suitable
      choice for low-concentration analytes from scarce biological samples. In our
      trap, ions can be cooled down to cryogenic temperatures to achieve higher
      resolution infrared spectra, and individual ions can be mass selected prior to
      irradiation for a background-free photodissociation scheme. Conveniently,
      multiple tagged analyte ions can be mass isolated and efficiently irradiated in
      the same experiment, allowing their infrared spectra to be recorded in parallel.
      This multiplexed approach is critical in terms of increasing the duty cycle of
      infrared ion spectroscopy, which is currently a key weakness of the technique.
      The compact design of this instrument, coupled with powerful mass selection
      capabilities, set the stage for making cryogenic infrared ion spectroscopy viable
      as a bioanalytical tool in small molecule identification.

PMID- 28750481
TI  - Aqueous shunts for glaucoma.
AB  - BACKGROUND: Aqueous shunts are employed to control intraocular pressure (IOP) for
      people with primary or secondary glaucomas who fail or are not candidates for
      standard surgery. OBJECTIVES: To assess the effectiveness and safety of aqueous
      shunts for reducing IOP in glaucoma compared with standard surgery, another type
      of aqueous shunt, or modification to the aqueous shunt procedure. SEARCH METHODS:
      We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register)
      (2016, Issue 8), MEDLINE Ovid (1946 to August 2016), Embase.com (1947 to August
      2016), PubMed (1948 to August 2016), LILACS (Latin American and Caribbean Health
      Sciences Literature Database) (1982 to August 2016), ClinicalTrials.gov
      (www.clinicaltrials.gov); searched 15 August 2016, and the World Health
      Organization (WHO) International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en); searched 15 August 2016. We did not use any date
      or language restrictions in the electronic search for trials. We last searched
      the electronic databases on 15 August 2016. We also searched the reference lists
      of identified trial reports and the Science Citation Index to find additional
      trials. SELECTION CRITERIA: We included randomized controlled trials that
      compared various types of aqueous shunts with standard surgery or to each other
      in eyes with glaucoma. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened search results for eligibility, assessed the risk of bias,
      and extracted data from included trials. We contacted trial investigators when
      data were unclear or not reported. We graded the certainty of the evidence using
      the GRADE approach. We followed standard methods as recommended by Cochrane. MAIN
      RESULTS: We included 27 trials with a total of 2099 participants with mixed
      diagnoses and comparisons of interventions. Seventeen studies reported adequate
      methods of randomization, and seven reported adequate allocation concealment.
      Data collection and follow-up times varied.Four trials compared an aqueous shunt
      (Ahmed or Baerveldt) with trabeculectomy, of which three reported one-year
      outcomes. At one-year, the difference in IOP between aqueous shunt groups and
      trabeculectomy groups was uncertain (mean difference (MD) 2.55 mmHg, 95%
      confidence interval (CI) -0.78 to 5.87; 380 participants; very low-certainty
      evidence). The difference in logMAR visual acuity was also uncertain (MD 0.12
      units, 95% CI -0.07 to 0.31; 380 participants; very low-certainty evidence). In
      two trials, the difference in visual field score was uncertain (MD -0.25, 95% CI 
      1.91 to 1.40; 196 participants; very low-certainty evidence). The mean number of
      antiglaucoma medications was higher in the aqueous shunt group than the
      trabeculectomy group in one trial (MD 0.80, 95% CI 0.48 to 1.12; 184
      participants; low-certainty evidence). The effect on needing additional glaucoma
      surgery was uncertain between groups in two trials (risk ratio (RR) 0.24, 95% CI
      0.04 to 1.36; 329 participants; very low-certainty evidence). In one trial, fewer
      total adverse events were reported in the aqueous shunt group than the
      trabeculectomy group (RR 0.59, 95% CI 0.43 to 0.81; 212 participants; very low
      certainty evidence). No trial reported quality-of-life outcomes at one-year
      follow-up.Two trials that compared the Ahmed implant with the Baerveldt implant
      for glaucoma found higher mean IOP in the Ahmed group at one-year follow-up (MD
      2.60 mmHg, 95% CI 1.58 to 3.62; 464 participants; moderate-certainty evidence).
      The difference in logMAR visual acuity was uncertain between groups (MD -0.07
      units, 95% CI -0.27 to 0.13; 501 participants; low-certainty evidence). The MD in
      number of antiglaucoma medications was within one between groups (MD 0.35, 95% CI
      0.11 to 0.59; 464 participants; moderate-certainty evidence). More participants
      in the Ahmed group required additional glaucoma surgery than the Baerveldt group
      (RR 2.77, 95% CI 1.02 to 7.54; 514 participants; moderate-certainty evidence).
      The two trials reported specific adverse events but not overall number of adverse
      events. Neither trial reported visual field or quality-of-life outcomes at one
      year follow-up.One trial compared the Ahmed implant with the Molteno implant for
      glaucoma over two-year follow-up. Mean IOP was higher in the Ahmed group than the
      Molteno group (MD 1.64 mmHg, 95% CI 0.85 to 2.43; 57 participants; low-certainty
      evidence). The differences in logMAR visual acuity (MD 0.08 units, 95% CI -0.24
      to 0.40; 57 participants; very low-certainty evidence) and mean deviation in
      visual field (MD -0.18 dB, 95% CI -3.13 to 2.77; 57 participants; very low
      certainty evidence) were uncertain between groups. The mean number of
      antiglaucoma medications was also uncertain between groups (MD -0.38, 95% CI 
      1.03 to 0.27; 57 participants; low-certainty evidence). The trial did not report
      the proportion needing additional glaucoma surgery, total adverse events, or
      quality-of-life outcomes.Two trials compared the double-plate Molteno implant
      with the Schocket shunt for glaucoma; one trial reported outcomes only at six
      month follow-up, and the other did not specify the follow-up time. At six-months,
      mean IOP was lower in the Molteno group than the Schocket group (MD -2.50 mmHg,
      95% CI -4.60 to -0.40; 115 participants; low-certainty evidence). Neither trial
      reported the proportion needing additional glaucoma surgery, total adverse
      events, or visual acuity, visual field, or quality-of-life outcomes.The remaining
      18 trials evaluated modifications to aqueous shunts, including 14 trials of Ahmed
      implants (early aqueous suppression versus standard medication regimen, 2 trials;
      anti-vascular endothelial growth factor agent versus none, 4 trials;
      corticosteroids versus none, 2 trials; shunt augmentation versus none, 3 trials;
      partial tube ligation versus none, 1 trial; pars plana implantation versus
      conventional implantation, 1 trial; and model M4 versus model S2,1 trial); 1
      trial of 500 mm2 Baerveldt versus 350 mm2 Baerveldt; and 3 trials of Molteno
      implants (single-plate with oral corticosteroids versus single-plate without oral
      corticosteroids, 1 trial; double-plate versus single-plate, 1 trial; and pressure
      ridge versus double-plate with tube ligation, 1 trial). AUTHORS' CONCLUSIONS:
      Information was insufficient to conclude whether there are differences between
      aqueous shunts and trabeculectomy for glaucoma treatment. While the Baerveldt
      implant may lower IOP more than the Ahmed implant, the evidence was of moderate
      certainty and it is unclear whether the difference in IOP reduction is clinically
      significant. Overall, methodology and data quality among existing randomized
      controlled trials of aqueous shunts was heterogeneous across studies, and there
      are no well-justified or widely accepted generalizations about the superiority of
      one surgical procedure or device over another.

PMID- 28750483
TI  - Advanced Colonic Neoplasia at Follow-up Colonoscopy According to Risk Components
      and Adenoma Location at Index Colonoscopy: A Retrospective Study of 1,974
      Asymptomatic Koreans.
AB  - Background/Aims: We aimed to estimate the cumulative incidence of advanced
      colonic neoplasia and analyze the risk factors for advanced colonic neoplasia
      according to risk components and adenoma location at index colonoscopy. Methods:
      We reviewed 1,974 subjects who underwent a follow-up colonoscopy after a complete
      screening colonoscopy and the removal of all polyps. We estimated the cumulative
      incidence of a subsequent advanced neoplasia according to risk groups (normal,
      low-risk, and high-risk). Risk factors were analyzed by risk components (>=3
      adenomas, adenoma >=1 cm, and villous-type adenoma) and adenoma location.
      Results: Overall, 111 advanced neoplasias (5.6%) were newly diagnosed at the
      follow-up colonoscopy. The 3-year cumulative incidences of advanced neoplasia
      were 0.8%, 3.1%, and 10.2% in the normal, low-risk, and high-risk groups,
      respectively (p<0.0001), and the 5-year cumulative incidences were 2.2%, 8.6%,
      and 20.2%, respectively (p<0.0001). Age >=60 years (hazard ratio [HR], 1.78; 95%
      confidence interval [CI], 1.21 to 2.63), right-sided colonic adenoma (HR, 1.74;
      95% CI, 1.13 to 2.66), >=3 adenomas (HR, 2.00; 95% CI, 1.22 to 3.28), and
      adenomas >=1 cm in size (HR, 2.03; 95% CI, 1.20 to 3.44) in the index colonoscopy
      were independent risk factors for subsequent development of advanced neoplasia.
      Conclusions: Right-sided colonic adenoma, >=3 adenomas, adenomas >=1 cm, and age
      >=60 years at the index colonoscopy were significant risk factors for advanced
      neoplasia following a complete screening colonoscopy and removal of all polyps.

PMID- 28750484
TI  - Reactivation of Hepatitis C Virus and Its Clinical Outcomes in Patients Treated
      with Systemic Chemotherapy or Immunosuppressive Therapy.
AB  - Background/Aims: According to the results of several studies, the outcome of
      hepatitis C virus (HCV) reactivation is not as severe as the outcome of hepatitis
      B virus reactivation. The aim of this study was to evaluate the effect of
      pharmacological immunosuppression on HCV reactivation. Methods: The medical
      records of patients who underwent systemic chemotherapy, corticosteroid therapy,
      or other immunosuppressive therapies between January 2008 and March 2015 were
      reviewed. Subsequently, 202 patients who were seropositive for the anti-HCV
      antibody were enrolled. Exclusion criteria were: unavailability of data on HCV
      RNA levels, a history of treatment for chronic hepatitis C, and the presence of
      liver diseases other than a chronic HCV infection. Results: Among the 120
      patients enrolled in this study, hepatitis was present in 46 patients (38%). None
      of the patients were diagnosed with severe hepatitis. Enhanced replication of HCV
      was noted in nine (27%) of the 33 patients who had data available on both basal
      and follow-up HCV RNA loads. Reappearance of the HCV RNA from an undetectable
      state did not occur after treatment. The cumulative rate of enhanced HCV
      replication was 23% at 1 year and 30% at 2 years. Conclusions: Although enhanced
      HCV replication is relatively common in HCV-infected patients treated with
      chemotherapy or immunosuppressive therapy, it does not lead to serious sequelae.

PMID- 28750485
TI  - In Vitro Activity of Diphenyleneiodonium toward Multidrug-Resistant Helicobacter
      pylori Strains.
AB  - Background/Aims: The increased resistance of Helicobacter pylori to antibiotics
      has increased the need to develop new treatments for this bacterium. The aim of
      our study was to identify new drugs with anti-H. pylori activity. Methods: We
      screened a small molecule library-the library of pharmacologically active
      compounds (LOPAC), which includes 1,280 pharmacologically active compounds-to
      identify inhibitors of H. pylori growth. The minimal inhibitory concentrations
      (MICs) of antibiotics against multidrug-resistant H. pylori strains were
      determined using the agar dilution method. Results: We identified
      diphenyleneiodonium (DPI) as a novel anti-H. pylori agent. The MIC values for DPI
      were <0.03 ug/mL against all tested H. pylori strains. DPI also exhibited strong
      antibacterial activity against common gram-negative and gram-positive pathogenic
      bacteria. Conclusions: DPI may be a candidate anti-H. pylori drug for future
      development.

PMID- 28750486
TI  - Assessment of the Risk of Colorectal Cancer Survivors Developing a Second Primary
      Pancreatic Cancer.
AB  - Background/Aims: We aimed to investigate the incidence of second primary
      pancreatic cancer (PC) after colorectal cancer (CRC) and to identify risk factors
      associated with subsequent PC. Methods: The observed incidence of a subsequent PC
      in patients with CRC was standardized using a population with CRC from the Korean
      Central Cancer Registry (KCCR). The expected incidence rate of PC was obtained by
      assuming that the select group experienced the same cancer incidence as the
      corresponding general population in the KCCR. Results: The registry included
      4,822 patients with CRC aged 45 to 74 years, representing 16,725.1 person-years
      of follow-up. Thirteen patients (0.3%) were diagnosed with a subsequent PC, and
      the overall age-adjusted incidence of second primary PC was 269.6 per 100,000
      cases. In contrast, the overall incidence of primary PC in the general population
      was 18.68 per 100,000 individuals. The standardized incidence ratio of subsequent
      PC was 14.44, which was significantly higher in patients with CRC than in the
      general population. Sex, diabetes mellitus, smoking, body mass index, and a
      history of receiving chemotherapy as a treatment for CRC did not increase the
      risk of subsequent development of PC. Conclusions: The risk of a second primary
      PC was higher in patients with CRC. Further studies are needed to identify the
      risk factors and generate a screening strategy for cancer survivors.

PMID- 28750487
TI  - The Effect of Intragastric Administration of Botulinum Toxin Type A on Reducing
      Adiposity in a Rat Model of Obesity Using Micro-CT and Histological Examinations.
AB  - Background/Aims: Botulinum toxin type A (BTX), a long-acting inhibitor of
      muscular contraction in both striated and smooth muscles, is responsible for
      gastric motility. The aim of this study was to investigate the effects of an
      endoscopic intragastric BTX injection on weight loss, body fat accumulation, and
      gastric emptying time. Methods: The BTX group consisted of 15 obese rats in which
      20 U of BTX were injected into the gastric antrum. The saline group consisted of
      15 obese rats injected with 20 U of saline, and the control group included 10
      obese rats that did not receive a surgical intervention. The gastric emptying
      time, biochemical parameters, and body fat volume were evaluated using micro
      computed tomography (micro-CT) and histologic evaluations. Results: The
      postoperative body weight of the BTX group was significantly lower than those of
      the other groups (p<0.001) at 6 weeks after the operation. The gastric emptying
      time (156+/-54 minutes) was significantly delayed in the BTX group. The BTX group
      showed significantly lower lipid levels than the other groups. A reduction in
      body fat volume was observed in the BTX group using micro-CT and histological
      evaluations. Conclusions: BTX application to the gastric antrum represents a
      potentially effective treatment for obesity and may help improve the lipid
      profile by increasing the gastric emptying time.

PMID- 28750488
TI  - Serum MicroRNA Levels as a Noninvasive Diagnostic Biomarker for the Early
      Diagnosis of Hepatitis B Virus-Related Liver Fibrosis.
AB  - Background/Aims: To investigate the role of selected serum microRNA (miRNA)
      levels as potential noninvasive biomarkers for differentiating S0-S2 (early
      fibrosis) from S3-S4 (late fibrosis) in patients with a chronic hepatitis B virus
      (HBV) infection. Methods: One hundred twenty-three treatment-naive patients with
      a chronic HBV infection who underwent a liver biopsy were enrolled in this study.
      The levels of selected miRNAs were measured using a real-time quantitative
      polymerase chain reaction assay. A logistic regression analysis was performed to
      assess factors associated with fibrosis progression. Receiver operating
      characteristic (ROC) curve and discriminant analyses validated these the ability
      of these predicted variables to discriminate S0-S2 from S3-S4. Results: Serum miR
      29, miR-143, miR-223, miR-21, and miR-374 levels were significantly downregulated
      as fibrosis progressed from S0-S2 to S3-S4 (p<0.05), but not miR-16. The
      multivariate logistic regression analysis identified a panel of three miRNAs and
      platelets that were associated with a high diagnostic accuracy in discriminating
      S0-S2 from S3-S4, with an area under the curve of 0.936. Conclusions: The levels
      of the studied miRNAs, with the exception of miR-16, varied with fibrosis
      progression. A panel was identified that was capable of discriminating S0-S2 from
      S3-S4, indicating that serum miRNA levels could serve as a potential noninvasive
      biomarker of fibrosis progression.

PMID- 28750489
TI  - Patients' Preferences for Primary Colorectal Cancer Screening: A Survey of the
      National Colorectal Cancer Screening Program in Korea.
AB  - Background/Aims: The adoption of colonoscopy as a primary colorectal cancer (CRC)
      screening technique has been argued for in Korea, without evidence of patient
      preferences. This study aimed to investigate patients' preferences for the
      primary CRC screening test for the National Cancer Screening Program (NCSP).
      Methods: Between June and August 2016, 414 individuals aged >=50 years who
      participated in the NCSP were prospectively invited to complete a questionnaire
      regarding their preferences for the primary CRC screening test and the reasons
      for their selection. Results: Among the 396 respondents who completed the
      questionnaire, 124 individuals (31.3%) preferred the fecal immunochemical test
      (FIT), whereas 272 individuals (68.7%) preferred colonoscopy. Elderly
      participants preferred the FIT (p<0.001), whereas participants with a higher
      education level (p=0.030), a higher income level (p=0.009), or individuals with a
      family member (p=0.028) or acquaintance (p=0.013) with a history of CRC preferred
      colonoscopy. Only 12.9% of participants had a bad experience with a previous FIT;
      however, 39.3% of participants had a bad experience with a previous colonoscopy.
      Conclusions: Colonoscopy was preferred to FIT in a 2.2:1 ratio as the primary CRC
      screening test for the NCSP. Patients' preference for colonoscopy should be
      considered for the NCSP in Korea.

PMID- 28750490
TI  - Secondary adrenal insufficiency: from the physiopathology to the possible role of
      modified-release hydrocortisone treatment.
AB  - Central adrenal insufficiency (AI) represents a life-threatening disorder that
      results from a reduced cortisol production due to an impairment production of
      adrenocorticotropic hormone (ACTH). In particular, secondary AI results from
      pituitary disease that impedes the release of ACTH, while tertiary AI is caused
      from an impaired synthesis of corticotropin-releasing hormone. Central AI has an
      estimated prevalence of 150-280 per million, resulting more common than primary
      AI. Prompt diagnosis and management of this condition is crucial, but the
      diagnostic investigation can often be challenging, in particular in cases of
      recent onset of secondary adrenal insufficiency. Moreover, different formulations
      of steroid replacement therapy are available for both primary and central adrenal
      insufficiency, but the therapy of choice for the treatment of secondary
      hypoadrenalism is still debated. In particular, several data confirm the
      advantages of dual-release hydrocortisone formulation in primary hypoadrenalism,
      while data for secondary AI are still lacking. However, in spite of few clinical
      data, the use of dual release hydrocortisone can be extremely favorable in ACTH
      deficiency, which is associated with an increase of overall and cardiovascular
      mortality, also due to the risk of overtreatment. In this condition, the use of a
      modified-release glucocorticoid formulation, which has been demonstrated to
      improve metabolic profile, can be extremely attractive.

PMID- 28750491
TI  - Severe Delayed Gastric Emptying Induces Non-acid Reflux up to Proximal Esophagus
      in Neurologically Impaired Patients.
AB  - Background/Aims: The aim of this study is to investigate the degree of delayed
      gastric emptying (DGE) and evaluate how the severity of DGE affects
      gastroesophageal reflux disease (GERD) in neurologically impaired (NI) patients
      utilizing 24-hour multichannel intraluminal impedance pH measurements (pH/MII)
      and 13C-acetate breath test (13C-ABT) analyses. Methods: 13C-ABT and pH/MII were
      conducted in 26 NI patients who were referred to our institution due to suspected
      GERD. At first, correlation analyses were performed to investigate the
      correlation between the 13C-ABT parameters and the clinical or pH/MII parameters.
      Thereafter, all patients were divided into 2 groups (DGE and severe DGE [SDGE]
      group) according to each cut off half emptying time (t1/2, 90-170 minutes). Each
      pH/MII parameter was compared between the 2 groups in each set-up cutoff t1/2.
      Results: The mean t1/2 of all patients was 215.5 +/- 237.2 minutes and the t1/2
      of 24 (92.3%) patients were > 100 minutes. Significant moderate positive
      correlations were observed between both t1/2 and lag phase time and the non-acid
      reflux related parameters. Furthermore, the patients in the SDGE group
      demonstrated higher non-acid reflux related parameters than those of the DGE
      groups when the cutoff was t1/2 >= 140 minutes. Conclusion: The present study
      demonstrated that GE with t1/2 >= 140 minutes was related to an increase of non
      acid exposure reaching up to the proximal esophagus in NI patients, and
      indicating that NI patients with SDGE might have a high risk of non-acid GERD.

PMID- 28750492
TI  - Parkinson disease-related cortical and striatal cognitive patterns in dual time F
      18 FP CIT: evidence for neural correlates between the caudate and the frontal
      lobe.
AB  - BACKGROUND: Using dual time F-18 FP-CIT, we evaluated cortical perfusion,
      striatal binding and neuropsychological performance simultaneously in Parkinson's
      disease (PD) with and without mild cognitive impairment (MCI), to investigate
      neural correlates between caudate and frontal cortex. METHODS: According to the
      neuropsychological scores, subjects were classified into 26 healthy controls
      (HC), 38 PD-MCI (executive) (PE), 24 PD-MCI (non-executive) (PN) and 21 PD
      (motor) (PM). Scans were acquired at 10 minutes and 2 hours. Group differences of
      early perfusion and delayed binding were compared using SPM and volume of
      interest method. The relationships between neuropsychological variables and the
      striatal binding were investigated with correlation and regression analysis.
      RESULTS: Compared with PM, PE showed decreased prefrontal perfusion and binding
      of both caudates (Right: p = 0.0010, Left: p = 0.014), but not of both putamens.
      Compared with PN, PE showed decreased binding of both caudates (Right: p = 0.001,
      Left: p = 0.005), but not in both putamens. Binding of both caudates correlated
      with the Stroop z-score, but not of both putamens. Executive score was a
      contributing factor to binding of the caudate, and not the putamen. CONCLUSIONS:
      PE showed decreased prefrontal perfusion and caudate binding, supporting neural
      correlates between the caudate and the prefrontal cortex. Dopaminergic binding of
      the caudate, but not of the putamen, was related to executive scores. Caudate
      hypofunction was specific to executive domain. This is the first study that
      elucidated the clinical use of dual time F-18 FP-CIT for integrative evaluation
      of cognitive and motor function in PD.

PMID- 28750493
TI  - Concomitant semi-quantitative and visual analysis improves the predictive value
      on treatment outcome of interim 18F-fluorodeoxyglucose / Positron Emission
      Tomography in advanced Hodgkin lymphoma.
AB  - BACKGROUND: Qualitative assessment using the Deauville five-point scale (DS) is
      the gold standard for interim and end-of treatment PET interpretation in
      lymphoma. In the present study we assessed the reliability and the prognostic
      value of different semi- quantitative (SQ) parameters in comparison with DS for
      interim PET (iPET) interpretation in Hodgkin lymphoma (HL). METHODS: A cohort of
      82 out of 260 patients with advanced stage HL enrolled in the International
      Validation Study (IVS), scored as 3 to 5 by the expert panel was included in the
      present report. Two nuclear medicine physicians blinded to patient history,
      clinical data and treatment outcome reviewed independently the iPET using the
      following parameters: DS, SUVMax, SUVPeak of the most active lesion, QMax (ratio
      of SUVMax of the lesion to liver SUVMax) and QRes (ratio of SUVPeak of the lesion
      to liver SUVMean). The optimal sensitivity, specificity, positive and negative
      predictive value to predict treatment outcome was calculated for all the above
      parameters with the Receiver Operator Characteristics analysis. RESULTS: The
      prognostic value of all parameters were similar, the best cut-off value being 4
      for DS (Area Under the Curve, AUC, 0.81 CI95%: 0.72-0.90), 3.81 for SUVMax (AUC
      0.82 CI95%: 0.73-0.91), 3.20 for SUVPeak (AUC 0.86 CI95%: 0.77-0.94), 1.07 for
      QMax (AUC 0.84 CI95%: 0.75-0.93) and 1.38 for QRes (AUC 0.84 CI95%: 0.75-0.93).
      The reproducibility of different parameters was similar as the inter-observer
      variability measured with Cohen's kappa were 0.93 (95% CI 0.84-1.01) for the DS,
      0.88 (0.77-0.98) for SUVMax, 0.82 (0.70-0.95) for SUVPeak, 0.85 (0.74-0.97) for
      QRes and 0.78 (0.65-0.92) for QMax. Due to the high specificity of SUVPeak (0.87)
      and to the good sensitivity of DS (0.86), upon the use of both parameters the
      positive predictive value increased from 0.65 of the DS alone to 0.79. When both
      parameters were positive in iPET, 3-years Failure-Free Survival (FFS) was
      significantly lower compared to patients whose iPET was interpreted with
      qualitative parameters only (DS 4 or 5): 21% vs 35%. On the other hand, the FFS
      of patients with negative results was not significantly different (88% vs 86%).
      CONCLUSIONS: In this study we demonstrated that, combining semi-quantitative
      parameters with SUVPeak to a pure qualitative interpretation key with DS, it is
      possible to increase the positive predictive value of iPET and to identify with
      higher precision the patients subset with a very dismal prognosis. However, these
      retrospective findings should be confirmed prospectively in a larger patient
      cohort.

PMID- 28750494
TI  - Brain PET and functional MRI: why simultaneously using hybrid PET/MR systems?
AB  - INTRODUCTION: In the last 20 years growing attention has been devoted to
      multimodal imaging. The recent literature is rich of clinical and research
      studies that have been performed using different imaging modalities on both
      separate and integrated positron emission tomography (PET) and magnetic resonance
      (MR) scanners. However, today, hybrid PET/MR systems measure signals related to
      brain structure, metabolism, neurochemistry, perfusion, and neuronal activity
      simultaneously, i.e. in the same physiological conditions. A frequently raised
      question at meeting and symposia is: "Do we really need a hybrid PET/MR system?
      Are there any advantages over acquiring sequential and separate PET and MR
      scans?" The present paper is an attempt to answer these questions specifically in
      relation to PET combined with functional magnetic resonance imaging (fMRI) and
      arterial spin labeling. EVIDENCE ACQUISITION: We searched (last update: June
      2017) the databases PubMed, PMC, Google Scholar and Medline. We also included
      additional studies if they were cited in the selected articles. No language
      restriction was applied to the search, but the reviewed articles were all in
      English. Among all the retrieved articles, we selected only those performed using
      a hybrid PET/MR system. We found a total of 17 papers that were selected and
      discussed in three main groups according to the main radiopharmaceutical used:
      18F-fluorodeoxyglucose (18F-FDG) (N.=8), 15O-water (15O-H2O) (N.=3) and
      neuroreceptors (N.=6). EVIDENCE SYNTHESIS: Concerning studies using 18F-FDG,
      simultaneous PET/fMRI revealed that global aspects of functional organization
      (e.g. graph properties of functional connections) are partially associated with
      energy consumption. There are remarkable spatial and functional similarities
      across modalities, but also discrepant findings. More work is needed on this
      point. There are only a handful of papers comparing blood flow measurements with
      PET 15O-H2O and MR arterial spin label (ASL) measures, and they show significant
      regional CBF differences between these two modalities. However, at least in one
      study the correlation at the level of gray, white matter, and whole brain is
      rather good (r=0.94, 0.8, 0.81 respectively). Finally, receptor studies show that
      simultaneous PET/fMRI could be a useful tool to characterize functional
      connectivity along with dynamic neuroreceptor adaptation in several physiological
      (e.g. working memory) or pathological (e.g. pain) conditions, with or without
      drug administrations. CONCLUSIONS: The simultaneous acquisition of PET (using a
      number of radiotracers) and functional MRI (using a number of sequences) offers
      exciting opportunities that we are just beginning to explore. The results thus
      far are promising in the evaluation of cerebral metabolism/flow, neuroreceptor
      adaptation, and network's energetic demand.

PMID- 28750495
TI  - Imaging biomarkers in Alzheimer's disease: added value in the clinical setting.
AB  - Over the last 20 years the availability of magnetic resonance imaging and
      positron-emission tomography technologies as well as of cerebrospinal fluid
      biomarkers has allowed research and clinical approach to Alzheimer's disease (AD)
      to move towards the earliest manifestations of the disease. This new approach
      resulted in an increasing knowledge about in-vivo biological and
      neuropathological processes of each phase of the AD-related damage from
      preclinical, to mild cognitive impairment, and finally to dementia due to AD. The
      present narrative review deals with the available data as well as with the
      unsolved issued related to the incorporation of AD biomarkers into the clinical
      practice. Ongoing research efforts aiming to better define and implement the use
      of imaging AD biomarkers in clinical practice according to a patient-centered
      approach and sustainability for clinical-care systems are also discussed.

PMID- 28750496
TI  - Tau imaging with PET: an overview of challenges, current progress, and future
      applications.
AB  - Folded and misfolded tau is common to many neurodegenerative conditions,
      collectively termed "tauopathies". In recent years, many efforts have contributed
      toward development of tau imaging agents to allow measurement of tau deposits in
      vivo using positron emission tomography (PET). The particularities of tau present
      some unique challenges for the development of tau imaging tracers. Most notably,
      these pertain to the predominantly intracellular nature of tau aggregations, the
      existence of six isoforms, multiple post-translational modification, and that tau
      is usually surrounded by larger concentrations of Abeta plaques. Nevertheless,
      significant progress has been made towards overcoming these issues and a number
      of tracers are now undergoing human trials. Once validated, tau imaging with PET
      will be a useful tool for the differential diagnosis and disease staging, as well
      as therapeutic trials of AD and non-AD tauopathies.

PMID- 28750498
TI  - Emerging clinical issues and multivariate analyses in PET investigations.
AB  - PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG-PET) has been gradually introduced
      in the diagnostic clinical criteria of the most prevalent neurodegenerative
      diseases. Moreover, an increasing amount of literature has shown that the
      information provided by FDG-PET enhances the sensitivity of standard imaging
      biomarkers in less frequent disorders in which an early differential diagnosis
      can be of paramount relevance for patient management and outcome. Therefore
      emerging uses of FDG-PET may be important in prion diseases, autoimmune
      encephalitis (AE) and amyotrophic lateral sclerosis. Interestingly, FDG-PET
      findings can also be observed in the early phases of these conditions, even in
      the presence of normal magnetic resonance imaging scans. Thalamic hypometabolism
      is a common finding in sporadic Creutzfeldt-Jacob disease and fatal familiar
      insomnia patients, with further cortical synaptic dysfunction in the former.
      Limbic and extra-limbic metabolic abnormalities (more often hypermetabolism) can
      be observed in AE, although specific patterns may be seen within different
      syndromes associated with antibodies that target neuronal surface or synaptic
      antigens. FDG-PET shows its usefulness by discriminating patients with
      amyotrophic lateral sclerosis associated to upper motor neuron onset that evolve
      to frontotemporal dementia. Besides visual and voxel based image analysis,
      multivariate analysis as interregional correlation analysis and
      independent/principal component analysis have been successfully implemented to
      PET images increasing the accuracy of the discrimination of neurodegenerative
      diseases. The clinical presentation and current diagnostic criteria of these
      neurologic disorders as well as the emerging usefulness of FDG-PET in the
      diagnostic workup are presented and discussed in this review.

PMID- 28750497
TI  - News and views on in-vivo imaging of neurotransmission using PET and MRI.
AB  - Molecular neuroimaging with PET is an integrated tool in psychiatry research and
      drug-development for as long as this modality has been available, in particular
      for studying neurotransmission and endogenous neurotransmitter release.
      Pharmacologic, behavioral and other types of challenges are currently applied to
      induce changes in neurochemical levels that can be inferred through their effects
      on changes in receptor binding and related outcome measures. Based on the
      availability of tracers that are sensitive for measuring neurotransmitter release
      these experiments have focused on the brain's dopamine system, while recent
      developments have extended those studies to other targets such as the serotonin
      or choline system. With the introduction of hybrid, truly simultaneous PET/MRI
      systems, in-vivo imaging of the dynamics of neuroreceptor signal transmission in
      the brain using PET and functional MRI (fMRI) has become possible. fMRI has the
      ability to provide information about the effects of receptor function that are
      complementary to the PET measurement. Dynamic acquisition of both PET and fMRI
      signals enables not only an in-vivo real-time assessment of neurotransmitter or
      drug binding to receptors but also dynamic receptor adaptations and receptor
      specific neurotransmission. While fMRI temporal resolution is comparatively fast
      in relation to PET, the timescale of observable biological processes is highly
      dependent on the kinetics of radiotracers and study design. Overall, the
      combination of the specificity of PET radiotracers to neuroreceptors, fMRI signal
      as a functional readout and integrated study design promises to expand our
      understanding of the location, propagation and connections of brain activity in
      health and disease.

PMID- 28750499
TI  - Exosomal miR-9-3p suppresses HBGF-5 expression and is a functional biomarker in
      hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer and
      the third leading cause of cancer-related death worldwide. Exosomes are secreted
      membrane vesicles that play important roles in various diseases by transporting
      proteins and RNAs, including microRNAs, between cells. However, the function of
      exosomal miRNA in HCC has not been fully investigated. METHODS: Exosomes were
      obtained from the sera by ultracentrifugation and were processed for transmission
      electron microscopy (TEM). Real time PCR were revealed changes of miRNA between
      patients and normal donors. Predicted targets of miRNA were described by
      bioinformatics analysis, luciferase reporter assay was used to confirmed whether
      miR-9-3p regulates target expression. And then miRNA were over-expressed in HCC
      cell line to study its function, western blotting were used to test expression of
      miRNA targets, Cell viability and proliferation were analyzed after over
      expressed miR-9-3p using MTT and BrdU assay. RESULTS: Serum exosomes from
      patients with HCC contained significantly lower levels of the miR-9-3p than did
      serum exosomes from normal donors, suggesting a potential role for this microRNA
      in HCC. Bioinformatics analysis identified fibroblast growth factor 5 (HBGF-5),
      which plays an important role in cell proliferation, as a potential miR-9-3p
      target mRNA. Luciferase reporter assay confirming that miR-9-3p can directly
      regulate HBGF-5 expression. Consistent with this finding, overexpression of miR-9
      3p in three HCC cell lines significantly downregulated HBGF-5 expression at both
      the mRNA and protein levels. Finally, overexpression of miR-9-3p reduced HCC cell
      viability and proliferation, and additionally reduced ERK1/2 expression,
      suggesting a potential mechanism by which miR-9-3p acts. CONCLUSIONS: These
      results provide new insight into the functions of miR-9-3p and HBGF-5 in HCC and
      identify miR-9-3p as a potential therapeutic target for HCC.

PMID- 28750500
TI  - Endoscopic ultrasound core needle for diagnosing of solid pancreatic lesions: is
      rapid on-site evaluation really necessary?
AB  - INTRODUCTION: Endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) has
      a crucial role in the diagnosis of solid pancreatic lesions and rapid on-site
      evaluation (ROSE) can increase its diagnostic yield. Rapid on-site evaluation is
      not always available and after EUS-FNA provides a cytology specimen with scant
      cellularity. Fine needle biopsy (FNB) specimens containing core tissue may
      theoretically overcome the limitations of EUS-FNA sampling. It could be
      hypothesized that EUS-FNB without ROSE could achieve the same adequacy and
      accuracy of EUS-FNB with ROSE. The aim of this review is to evaluate the evidence
      on the role of ROSE in the setting of EUS-guided tissue acquisition with core
      needles in patients with solid pancreatic lesions. EVIDENCE ACQUISITION: All
      relevant articles were extracted up to February 2017 based on the results of
      searches in PubMed, Scopus and Google Scholar. EVIDENCE SYNTHESIS: A total of 21
      pertinent articles were finally included. Among the included studies, 11 were
      performed without ROSE, 8 with ROSE, and 2 were performed both with and without
      ROSE. In the ROSE group we found a sensitivity, specificity, overall diagnostic
      adequacy and overall diagnostic accuracy of 96%, 100%, 86.5%, 85.5%,
      respectively, while in the no-ROSE group 86.6%, 100%, 89.5%, 86.1% were found,
      respectively. Mild pancreatitis (mean rates, 3.43%) and abdominal pain (mean
      rates, 3.6%) were reported as most frequent adverse events. CONCLUSIONS:
      Endoscopic ultrasound guided-FNB without ROSE offers similar results in terms of
      adequacy and accuracy as in the presence of an on-site cytopathologist.

PMID- 28750501
TI  - The current management of kidney disease in the elderly.
AB  - Chronic kidney disease (CKD), diabetes and cardiovascular disease constitute
      three interrelated conditions of strong public health relevance. Elderly
      individuals account for the largest and the most rapidly growing age segment of
      the end-stage renal disease population. The elderly are affected by the same
      types of kidney diseases as younger individuals, but aging itself is associated
      with a gradual reduction in estimated glomerular filtration rate, which leads to
      the diminishment of the functional reserve and makes an individual more
      vulnerable to injurious effects of hypertension, cardiovascular disease,
      diabetes, and drugs' toxicity. Although the spectrum of diseases affecting people
      aged >=65 is the same as in younger population, there are some distinct
      differences in the frequency of certain nephropathies between these two age
      groups. The superimposition of aging-related lesions on other kidney diseases
      evolving in the elderly population makes the clinical picture more complex and
      reaching diagnosis more challenging. In elderly CKD patients the high prevalence
      of comorbidities and the often aberrant metabolism of medications have to be
      considered in individually tailored treatment strategies.

PMID- 28750502
TI  - Geographic and demographic variabilities of quantitative parameters in stress
      myocardial computed tomography perfusion.
AB  - BACKGROUND/AIMS: To evaluate the geographic and demographic variabilities of the
      quantitative parameters of computed tomography perfusion (CTP) of the left
      ventricular (LV) myocardium in patients with normal coronary artery on computed
      tomography angiography (CTA). METHODS: From a multicenter CTP registry of stress
      and static computed tomography, we retrospectively recruited 113 patients (mean
      age, 60 years; 57 men) without perfusion defect on visual assessment and minimal
      (< 20% of diameter stenosis) or no coronary artery disease on CTA. Using
      semiautomatic analysis software, quantitative parameters of the LV myocardium,
      including the myocardial attenuation in stress and rest phases, transmural
      perfusion ratio (TPR), and myocardial perfusion reserve index (MPRI), were
      evaluated in 16 myocardial segments. RESULTS: In the lateral wall of the LV
      myocardium, all quantitative parameters except for MPRI were significantly higher
      compared with those in the other walls. The MPRI showed consistent values in all
      myocardial walls (anterior to lateral wall: range, 25% to 27%; p = 0.401). At the
      basal level of the myocardium, all quantitative parameters were significantly
      lower than those at the mid- and apical levels. Compared with men, women had
      significantly higher values of myocardial attenuation and TPR. Age, body mass
      index, and Framingham risk score were significantly associated with the
      difference in myocardial attenuation. CONCLUSIONS: Geographic and demographic
      variabilities of quantitative parameters in stress myocardial CTP exist in
      healthy subjects without significant coronary artery disease. This information
      may be helpful when assessing myocardial perfusion defects in CTP.

PMID- 28750503
TI  - Protein and vitamin B6 intake are associated with liver steatosis assessed by
      transient elastography, especially in obese individuals.
AB  - BACKGROUND/AIMS: Although the detrimental effects of several dietary components
      on the promotion of nonalcoholic fatty liver disease are well known, no studies
      have assessed the role of dietary vitamin B6. Moreover, studies on the
      associations between dietary components or body composition indices and liver
      steatosis assessed by transient elastography are rare. Our aim was to identify
      the nutritional factors and anthropometric parameters associated with liver
      steatosis. METHODS: In this cross-sectional study, we enrolled 168 individuals
      (35% obese) who underwent a liver steatosis assessment by Controlled Attenuation
      Parameter measurement and nutritional assessment. RESULTS: Tertiles of vitamin B6
      intake were positively associated with hepatic steatosis (B=1.89, P=0.026,
      confidence interval [CI] 0.03-0.80) as well as with triglycerides, glucose,
      alanine aminotransferase (ALT), and body mass index . In obese individuals, after
      multivariable analysis, the Controlled Attenuation Parameter score was still
      associated with triglycerides, ALT, and total protein intake (B=0.56, P=0.01, CI
      0.10-1.02). Participants in tertile I (low intake) had a lower Controlled
      Attenuation Parameter than those in tertile III (P=0.01). CONCLUSIONS: We found a
      positive association between hepatic steatosis or Controlled Attenuation
      Parameter score and vitamin B6/total protein intake, probably related to the high
      intake of meat. Vitamin B6 might have a pathogenic role related to the increase
      of hepatic steatosis.

PMID- 28750504
TI  - Does myofascial and trigger point treatment reduce pain and analgesic intake in
      patients undergoing onabotulinumtoxinA injection due to chronic intractable
      migraine?
AB  - BACKGROUND: Chronic migraine is a disabling disorder associated with myofascial
      and trigger point disorders in the neck. Pharmacological management is the first
      line of treatment; however, rehabilitation procedures aimed at lessening symptoms
      of myofascial and trigger point disorders may add value in the management of
      headache symptoms. AIM: The aim of this study was to evaluate the feasibility of
      myofascial and trigger point treatment in chronic migraine patients receiving
      prophylactic treatment with onabotulinumtoxinA. To evaluate the treatment effects
      on headache frequency and intensity, analgesic consumption, cervical range of
      motion, trigger point pressure pain threshold, quality of life, and disability.
      DESIGN: Pilot, single-blind randomized controlled trial with two parallel groups.
      SETTING: Neurorehabilitation Unit. POPULATION: Twenty-two outpatients with
      chronic migraine. METHODS: Patients were randomly assigned to receive either
      cervicothoracic manipulative treatment (N.=12) or transcutaneous electrical nerve
      stimulation (TENS) in the upper trapezius (N.=10). Treatment consisted of 4
      sessions (30 min/session, 1 session/week for 4 weeks). A rater blinded to
      treatment allocation evaluated outcomes before treatment, during treatment, and 1
      month after the end of treatment. Consistent with the pilot nature of the study,
      feasibility was considered the primary outcome and efficacy the secondary
      outcome. RESULTS: All patients completed the study. No adverse events were
      reported. No significant between-group differences in pain intensity were
      observed during the study period. At post-treatment evaluation, the total
      consumption of analgesics (P=0.02) and non-steroidal anti-inflammatory (P=0.02)
      drugs was significantly lower in the manipulative treatment group than in the
      TENS group. These effects paralleled significant improvements in trigger point
      sensitivity and cervical active range of motion. CONCLUSIONS: Manipulative
      techniques aimed at reducing peripheral nociceptive triggers might add value in
      the management of chronic migraine symptoms and lower acute medication use.
      CLINICAL REHABILITATION IMPACT: An interdisciplinary approach comprising
      pharmacological and non-pharmacological strategies can reduce analgesic
      consumption and myofascial dysfunction symptoms in chronic migraine patients.

PMID- 28750505
TI  - Protective Effects of the Ethanol Extract of Viola tianshanica Maxim against
      Acute Lung Injury Induced by Lipopolysaccharides in Mice.
AB  - Viola tianshanica Maxim, belonging to the Violaceae plant family, is
      traditionally used in Uighur medicine for treating pneumonia, headache, and
      fever. There is, however, a lack of basic understanding of its pharmacological
      activities. This study was designed to observe the effects of the ethanol extract
      (TSM) from Viola tianshanica Maxim on the inflammation response in acute lung
      injury (ALI) induced by LPS and the possible underlying mechanisms. We found that
      TSM (200 and 500 mg/kg) significantly decreased inflammatory cytokine production
      and the number of inflammatory cells, including macrophages and neutrophils, in
      bronchoalveolar lavage fluid. TSM also markedly inhibited the lung wet-to-dry
      ratio and alleviated pathological changes in lung tissues. In vitro, after TSM
      (12.5-100 MUg/ml) treatment to RAW 264.7 cells for 1 h, LPS (1 MUg/ml) was added
      and the cells were further incubated for 24 h. TSM dose-dependently inhibited the
      levels of proinflammatory cytokines, such as NO, PGE2, TNF-alpha, IL-6, and IL
      1beta, and remarkably decreased the protein and mRNA expression of TNF-alpha and
      IL-6 in LPS-stimulated RAW 264.7 cells. TSM also suppressed protein expression of
      p-IkappaBa and p-ERK1/2 and blocked nuclear translocation of NF-kappaB p65. The
      results indicate that TSM exerts anti-inflammatory effects related with
      inhibition on NF-kappaB and MAPK (p-ERK1/2) signaling pathways. In conclusion,
      our data demonstrate that TSM might be a potential agent for the treatment of
      ALI.

PMID- 28750506
TI  - Microbial Communities and Physicochemical Properties of Myeolchi Jeotgal (Anchovy
      Jeotgal) Prepared with Different Types of Salts.
AB  - Myeolchi jeotgals (MJs) were prepared with purified salt (PS), solar salt aged
      for 1 year (SS), and bamboo salt (BS) melted 3 times at 10% and 20% (w/w)
      concentrations, and fermented for 28 weeks at 15 degrees C. BS MJ showed higher
      pH and lower titratable acidities than the other samples because of the
      alkalinity of bamboo salt. Lactic acid bacteria counts increased until 4-6 weeks
      and then decreased gradually, and were not detected after 20 weeks from MJs with
      10% salt. Yeast counts of PS MJs were higher than those of BS and SS MJs. Bacilli
      were detected in relatively higher numbers throughout the 28 weeks, like marine
      bacteria, but archae were detected in lower numbers during the first 10 weeks.
      When 16S rRNA genes were amplified from total DNA from PS MJ (10% salt) at 12
      weeks, Tetragenococcus halophilus was the major species. However, Staphylococcus
      epidermidis was the dominant species for BS MJ at the same time point. In SS MJ,
      T. halophilus was the dominant species and S. epidermidis was the next dominant
      species. BS and SS MJs showed higher amino-type nitrogen, ammonia-type nitrogen,
      and volatile basic nitrogen contents than PS MJs. SS and BS were better than PS
      for the production of high-quality MJs.

PMID- 28750507
TI  - Improved Biosurfactant Production by Bacillus subtilis SPB1 Mutant Obtained by
      Random Mutagenesis and Its Application in Enhanced Oil Recovery in a Sand System.
AB  - Biosurfactants or microbial surfactants are surface-active biomolecules that are
      produced by a variety of microorganisms. Biodegradability and low toxicity have
      led to the intensification of scientific studies on a wide range of industrial
      applications for biosurfactants in the field of environmental bioremediation as
      well as the petroleum industry and enhanced oil recovery. However, the major
      issues in biosurfactant production are high production cost and low yield.
      Improving the bioindustrial production processes relies on many strategies, such
      as the use of cheap raw materials, the optimization of medium-culture conditions,
      and selecting hyperproducing strains. The present work aims to obtain a mutant
      with higher biosurfactant production through applying mutagenesis on Bacillus
      subtilis SPB1 using a combination of UV irradiation and nitrous acid treatment.
      Following mutagenesis and screening on blood agar and subsequent formation of
      halos, the mutated strains were examined for emulsifying activity of their
      culture broth. A mutant designated B. subtilis M2 was selected as it produced
      biosurfactant at twice higher concentration than the parent strain. The potential
      of this biosurfactant for industrial uses was shown by studying its stability to
      environmental stresses such as pH and temperature and its applicability in the
      oil recovery process. It was practically stable at high temperature and at a wide
      range of pH, and it recovered above 90% of motor oil adsorbed to a sand sample.

PMID- 28750508
TI  - In Vitro Evidence of Anti-Inflammatory and Anti-Obesity Effects of Medium-Chain
      Fatty Acid-Diacylglycerols.
AB  - Dietary approaches using structured lipids, including medium-chain fatty acids
      and diacylglycerols, have been adopted for the prevention of obesity-induced
      chronic inflammation. In an extension to previous studies, medium-chain fatty
      acid-diacylglycerol enriched dietary oil (MCDG) was prepared by
      interesterification of canola oil and mediumchain fatty acid-triacylglycerols.
      The consequent MCDG product was applied to RAW264.7 macrophages followed by the
      assessment of multiple inflammatory responses. Compared with conventionally used
      canola and olive oil controls, MCDG suppressed macrophage phagocytosis, as
      assessed by the uptake of microsphere beads. Furthermore, the production of IL-6
      and TNF-alpha, transcription of COX-2 and iNOS, and expression of CD80 on cell
      surfaces were downregulated by MCDG in LPS-stimulated macrophages. Subsequently,
      differentiated 3T3-L1 adipocytes were evaluated for proinflammatory cytokine
      production and lipid accumulation. IL-6 production was marginally affected and
      lipid accumulation was inhibited by MCDG. Taken together, these results suggest
      that MCDG has potential as an alternative oil for cooking in order to prevent
      obesity-induced inflammation.

PMID- 28750509
TI  - Photochemically Generated Thiyl Free Radicals Observed by X-ray Absorption
      Spectroscopy.
AB  - Sulfur-based thiyl radicals are known to be involved in a wide range of chemical
      and biological processes, but they are often highly reactive, which makes them
      difficult to observe directly. We report herein X-ray absorption spectra and
      analysis that support the direct observation of two different thiyl species
      generated photochemically by X-ray irradiation. The thiyl radical sulfur K-edge X
      ray absorption spectra of both species are characterized by a uniquely low energy
      transition at about 2465 eV, which occurs at a lower energy than any previously
      observed feature at the sulfur K-edge and corresponds to a 1s->3p transition to
      the singly occupied molecular orbital of the free radical. Our results constitute
      the first observation of substantial levels of thiyl radicals generated by X-ray
      irradiation and detected by sulfur K-edge X-ray absorption spectroscopy.

PMID- 28750510
TI  - A Selective Cation Exchange Strategy for the Synthesis of Colloidal Yb3+-Doped
      Chalcogenide Nanocrystals with Strong Broadband Visible Absorption and Long-Lived
      Near-Infrared Emission.
AB  - Doping lanthanide ions into colloidal semiconductor nanocrystals is a promising
      strategy for combining their sharp and efficient 4f-4f emission with the strong
      broadband absorption and low-phonon-energy crystalline environment of
      semiconductors to make new solution-processable spectral-conversion
      nanophosphors, but synthesis of this class of materials has proven
      extraordinarily challenging because of fundamental chemical incompatibilities
      between lanthanides and most intermediate-gap semiconductors. Here, we present a
      new strategy for accessing lanthanide-doped visible-light-absorbing semiconductor
      nanocrystals by demonstrating selective cation exchange to convert precursor Yb3+
      doped NaInS2 nanocrystals into Yb3+-doped PbIn2S4 nanocrystals. Excitation
      spectra and time-resolved photoluminescence measurements confirm that Yb3+ is
      both incorporated within the PbIn2S4 nanocrystals and sensitized by visible-light
      photoexcitation of these nanocrystals. This combination of strong broadband
      visible absorption, sharp near-infrared emission, and long (>400 MUs) emission
      lifetimes in a colloidal nanocrystal system opens promising new opportunities for
      both fundamental-science and next-generation spectral-conversion applications
      such as luminescent solar concentrators.

PMID- 28750511
TI  - Reconfigurable Pipet for Customized, Cost-Effective Liquid Handling.
AB  - We have developed a multichannel air displacement pipet with reconfigurable
      channels for nonstandard liquid handling applications. While linear multichannel
      pipets enable many established assays, they do not support analytical tools with
      customized liquid holding geometries, specifically paper-based microfluidic
      devices. Using our pipet, complex paper-based microfluidic devices can be
      fabricated without requiring multiple, time-consuming motions with a single
      channel pipet or device designs limited to the configurations of traditional
      multichannel pipets. We created this tool by modifying a commercial 8-channel
      pipet using machined and 3D-printed components. We demonstrate the quantitative
      capabilities of our tool by comparing its performance to that of a calibrated,
      single-channel pipet in volume delivery experiments. Our reconfigurable pipet
      supports the advancement of custom analytical tools with nonstandard liquid
      handling requirements and provides an ergonomic alternative to commercial
      equipment for developers of paper-based devices.

PMID- 28750512
TI  - Finely Composition-Tunable Synthesis of Ultrafine Wavy PtRu Nanowires as
      Effective Electrochemical Sensors for Dopamine Detection.
AB  - Preparing Pt-based one-dimensional (1D) ultrafine nanowires with abundant
      structural defects/grain boundaries and exploring their novel applications have
      attracted great interest in real-world applications. Here we introduce an
      environmentally friendly, facile aqueous solution approach to directly prepare a
      series of sub-3.0 nm PtRu ultrafine wavy nanowires. Characterizations show that
      the PtRu nanowires are alloy polycrystalline structures with abundant structural
      defects/grain boundaries. We first introduce the as-synthesized PtRu nanowires
      into electrochemical biosensors for the detection of DA and find that the Pt7Ru3
      nanowires exhibit excellent electrocatalytic activity to DA with fast response,
      ultralow limit of detection, and excellent selectivity at a potential of 0.3 V in
      0.1 M phosphate buffered solution (pH 7.2). This study shows an effective
      approach to the development of ultrafine PtRu nanowires as electrocatalysts for
      electrochemical nonenzymatic dopamine biosensors.

PMID- 28750513
TI  - A DNA Walker as a Fluorescence Signal Amplifier.
AB  - Sensing nucleic acids typically involves the recognition of a specific sequence
      and reporting by, for example, a fluorogenic reaction yielding one activated dye
      molecule per detected nucleic acid. Here, we show that after binding to a DNA
      origami track a bound DNA target (a "DNA walker") can release the fluorescence of
      many molecules by acting as the catalyst of an enzymatic nicking reaction. As the
      walking kinetics sensitively depends on the walker sequence, the resulting
      brightness distribution of DNA origamis is a sequence fingerprint with single
      nucleotide sensitivity. Using Monte Carlo simulations, we rationalize that the
      random self-avoiding walk is mainly terminated when steps to nearest neighbors
      are exhausted. Finally, we demonstrate that the DNA walker is also active in a
      plasmonic hotspot for fluorescence enhancement, indicating the potential of
      combining different amplification mechanisms enabled by the modularity of DNA
      nanotechnology.

PMID- 28750514
TI  - Rapid and Clean Covalent Attachment of Methylsiloxane Polymers and Oligomers to
      Silica Using B(C6F5)3 Catalysis.
AB  - The rapid, room-temperature covalent attachment of alkylhydridosilanes (R3Si-H)
      to silicon oxide surfaces to form monolayers using tris(pentafluorophenyl)borane
      (B(C6F5)3, BCF) catalysis has recently been described. This method, unlike
      alternative routes to monolayers, produces only unreactive H2 gas as a byproduct
      and reaches completion within minutes. We report the use of this selective
      reaction between surface silanols and hydridosilanes to prepare surface-grafted
      poly(dimethylsiloxane)s (PDMSs) with various graft architectures that are
      controlled by the placement of hydridosilane functionality at one end, both ends,
      or along the chain of PDMS samples of controlled molecular weight. We also report
      studies of model methylsiloxane monolayers prepared from pentamethyldisiloxane,
      heptamethyltrisiloxane (two isomers), heptamethylcyclotetrasiloxane, and
      tris(trimethylsiloxy)silane. These modified silica surfaces with structurally
      defined methylsiloxane groups are not accessible by conventional silane surface
      chemistry and proved to be useful in exploring the steric limitations of the
      reaction. Linear monohydride- and dihydride-terminated PDMS-grafted surfaces
      exhibit increasing thickness and decreasing contact angle hysteresis with
      increasing molecular weight up to a particular molecular weight value. Above this
      value, the hysteresis increases with increasing molecular weight of end-grafted
      polymers. Poly(hydridomethyl-co-dimethylsiloxane)s with varied hydride content (3
      100 mol %) exhibit decreasing thickness, decreasing contact angle, and increasing
      contact angle hysteresis with increasing hydride content. These observations
      illustrate the importance of molecular mobility in three-phase contact line
      dynamics on low-hysteresis surfaces. To calibrate our preparative procedure
      against both monolayers prepared by conventional approaches as well as the recent
      reports, a series of trialkylsilane (mostly, n-alkyldimethylsilane) monolayers
      was prepared to determine the reaction time required to achieve the maximum
      bonding density using dynamic contact angle analysis. Monolayers prepared from
      hydridosilanes with BCF catalysis have lower bonding densities than those derived
      from chlorosilanes, and the reactions are more sensitive to alkyl group sterics.
      This lower bonding density renders greater flexibility to the n-alkyl groups in
      monolayers and can decrease the contact angle hysteresis.

PMID- 28750516
TI  - Celebrating Electrochemical Sensors at the 2017 Matrafured Meeting.

PMID- 28750515
TI  - Highly Sensitive, Label-Free Detection of 2,4-Dichlorophenoxyacetic Acid Using an
      Optofluidic Chip.
AB  - A highly sensitive approach for rapid and label-free detection of the herbicide
      2,4-dichlorophenoxyacetic acid (2,4-D) using an optofluidic chip is demonstrated.
      The optofluidic chip is prepared by covalent immobilization of 2,4-D-bovine serum
      albumin (2,4-D-BSA) conjugate to an integrated microring resonator. Subsequent
      detection of 2,4-D carried out in a competitive immunoreaction format enables
      selective detection of 2,4-D in different types of water samples, including
      bottled, tap, and lake water, at a limit of detection (LOD) of 4.5 pg/mL and in a
      quantitative range of 15-105 pg/mL. The microring resonator-based optofluidic
      chip is reusable with ultrahigh sensitivity that offers real-time and on-site
      detection of low-molecular-weight targets for potential applications in food
      safety and environmental monitoring.

PMID- 28750517
TI  - Highly Efficient Gas Sensor Using a Hollow SnO2 Microfiber for Triethylamine
      Detection.
AB  - Triethylamine (TEA) gas sensors having excellent response and selectivity are in
      great demand to monitor the real environment. In this work, we have successfully
      prepared a hollow SnO2 microfiber by a unique sustainable biomass conversion
      strategy and shown that the microfiber can be used in a high-performance gas
      sensor. The sensor based on the hollow SnO2 microfiber shows a quick
      response/recovery toward triethylamine. The response of the hollow SnO2
      microfiber is up to 49.5 when the concentration of TEA gas is 100 ppm. The limit
      of detection is as low as 2 ppm. Furthermore, the sensor has a relatively low
      optimal operation temperature of 270  degrees C, which is lower than those of
      many other reported sensors. The excellent sensing properties are largely
      attributed to the high sensitivity provided by SnO2 and the good permeability and
      conductivity of the one-dimensional hollow structure. Thus, the hollow SnO2
      microfiber using sustainable biomass as a template is a significant strategy for
      a unique TEA gas sensor.

PMID- 28750518
TI  - Ultrasensitive Detection of Protein with Wide Linear Dynamic Range Based on Core
      Shell SERS Nanotags and Photonic Crystal Beads.
AB  - Detection of proteins in a wide concentration range from fg mL-1 to sub mg mL-1
      is a challenge in the high throughput analysis of precision medicine. Herein, we
      proposed a biosensor consisting of core-shell surface-enhanced Raman scattering
      (SERS) nanotags as labels and photonic crystal beads (PCBs) as carriers for
      ultrasensitive detection of proteins. In practice, Raman dyes (RDs) were embedded
      in the interface of gold core and silver shell in the bimetal nanoparticles to
      form SERS nanotags. It was found that the sensitivity was significantly improved
      due to the enhanced Raman signal by the coupling of the core-shell structure and
      linear dynamic range (LDR) was extended owing to the high surface to volume ratio
      of PCBs as well. In addition, we also demonstrated that the biosensor exhibited
      fine stability and low background, which has great application potential in the
      detection of protein biomarkers.

PMID- 28750519
TI  - PCR Technologies for Point of Care Testing: Progress and Perspectives.
AB  - Since the Human Genome Project completed in 2000, the sequencing of the first
      genome, massive progress has been made by medical science in the early diagnosis
      and personalized therapies based on nucleic acids (NA) analysis. To allow the
      extensive use of these molecular methods in medical practice, scientific research
      is nowadays strongly focusing on the development of new miniaturized and easy-to
      use technologies and devices allowing fast and low cost NA analysis in
      decentralized environments. It is now the era of so-called genetic "Point-of
      Care" (PoC). These systems must integrate and automate all steps necessary for
      molecular analysis such as sample preparation (extraction and purification of NA)
      and detection based on PCR (Polymerase Chain Reaction) technology in order to
      perform, by unskilled personnel, in vitro genetic analysis near the patient (in
      hospital, in the physician office, clinic, or home), with rapid answers and low
      cost. In this review, the recent advances in genetic PoC technologies are
      discussed, including the extraction and PCR amplification chemistry suitable for
      PoC use and the new frontiers of research in this field.

PMID- 28750520
TI  - A Wearable and Highly Sensitive Graphene Strain Sensor for Precise Home-Based
      Pulse Wave Monitoring.
AB  - Profuse medical information about cardiovascular properties can be gathered from
      pulse waveforms. Therefore, it is desirable to design a smart pulse monitoring
      device to achieve noninvasive and real-time acquisition of cardiovascular
      parameters. The majority of current pulse sensors are usually bulky or
      insufficient in sensitivity. In this work, a graphene-based skin-like sensor is
      explored for pulse wave sensing with features of easy use and wearing comfort.
      Moreover, the adjustment of the substrate stiffness and interfacial bonding
      accomplish the optimal balance between sensor linearity and signal sensitivity,
      as well as measurement of the beat-to-beat radial arterial pulse. Compared with
      the existing bulky and nonportable clinical instruments, this highly sensitive
      and soft sensing patch not only provides primary sensor interface to human skin,
      but also can objectively and accurately detect the subtle pulse signal variations
      in a real-time fashion, such as pulse waveforms with different ages, pre- and
      post-exercise, thus presenting a promising solution to home-based pulse
      monitoring.

PMID- 28750521
TI  - Plasmon Field-Enhanced Fluorescence Energy Transfer for Hairpin Aptamer Assay
      Readout.
AB  - Surface plasmon field-enhanced fluorescence energy transfer is employed for
      sensitive optical readout of a reversible hairpin aptamer assay that is suitable
      for continuous monitoring of low-molecular-weight chemical analytes. A hairpin
      aptamer specific to adenosine and adenosine triphosphate with Alexa Fluor 647
      fluorophore attached to its 5' end was anchored via 3' end thiol to a gold thin
      film. Molecular spacers were used to control the distance of the fluorophore from
      the surface in the aptamer "off" and "on" states. The specific binding of the
      target analyte changes the aptamer conformation, which alters the distance of the
      fluorophore from the gold surface and translates to variations in the detected
      fluorescence intensity. The plasmonically mediated fluorescence signal increases
      the measured signal-to-noise ratio and allows for real-time observation of the
      analyte binding. Theoretical as well as experimental study of the optical signal
      dependence on fluorophore orientation, design of spacers, and angular
      distribution of collected light is presented for rational design of the assay.
      The detected sensor signal increased by a factor as large as 23 upon switching
      the aptamer from the "off" to "on" state due to the hairpin opening associated
      with the specific capture of target analyte.

PMID- 28750522
TI  - Luminescent Probes for Sensitive Detection of pH Changes in Live Cells through
      Two Near-Infrared Luminescence Channels.
AB  - Two water-soluble near-infrared luminescent probes, which possess both
      conventional intense Stokes fluorescence and unique single-photon frequency
      upconversion luminescence (FUCL), were developed for sensitive and selective
      detection of pH changes in live cells. The water solubility and biocompatibility
      of these probes were achieved by introducing mannose residues through 2,2'
      (ethylenedioxy)diethylamine tethered spacers to a near-infrared conventional
      fluorescence (CF) and FUCL organic fluorophore. At a pH higher than 7.4, the
      probes have ring-closed spirocyclic lactam structures, thus are colorless and
      nonfluorescent. Nevertheless, they sensitively respond to acidic pH values, with
      a drastic structural change to ring-opened spirocyclic lactam forms, which cause
      significant absorbance increases at 714 nm. Correspondingly, their near-infrared
      CF and FUCL intensities at 740 nm are also significantly enhanced when excited by
      690 and 808 nm, respectively. The probes hold a variety of advantages such as
      high sensitivity, excellent reversibility and selectivity to pH over metal ions,
      low cellular autofluorescence background interference, good cell membrane
      permeability and photostability, as well as low cytotoxicity. Our results have
      successfully proven that these probes can visualize intracellular lysosomal pH
      changes in live cells by monitoring both near-infrared CF and FUCL changes.

PMID- 28750523
TI  - Aptamer-Embedded Zirconium-Based Metal-Organic Framework Composites Prepared by
      De Novo Bio-Inspired Approach with Enhanced Biosensing for Detecting Trace
      Analytes.
AB  - A series of Zr-based metal-organic framework (MOF) composites embedded with three
      kinds of aptamer strands (509-MOF@Apt) were achieved by a one-step de novo
      synthetic approach. A platform for ultrasensitive detection of analytes, namely,
      thrombin, kanamycin, and carcinoembryonic antigen (CEA), was also established.
      Considering the conformational changes caused by the binding interactions between
      aptamer strands and targeted molecules, the label-free electrochemical
      aptasensors based on 509-MOF@Apt composites could be developed to detect various
      target molecules. By comparing the common fabrication approaches of aptasensors,
      a distinct determination mechanism was presented through analysis of the
      electrochemical measurements on different interaction behaviors between probe
      aptamer strands and 509-MOF materials. The optimized aptasensors based on 509
      MOFs@Apt demonstrated excellent sensitivity (with the detection limit of 0.40,
      0.37, and 0.21 pg mL-1 for CEA, thrombin, and kanamycin, respectively),
      stability, repeatability, and applicability. This work will provide a new
      platform for direct and feasible detection in biosensing related to clinical
      diagnostics and therapeutics, and further, extend the scope of potential
      applications for MOF materials.

PMID- 28750524
TI  - Nanolock-Nanopore Facilitated Digital Diagnostics of Cancer Driver Mutation in
      Tumor Tissue.
AB  - Cancer driver mutations are clinically significant biomarkers. In precision
      medicine, accurate detection of these oncogenic changes in patients would enable
      early diagnostics of cancer, individually tailored targeted therapy, and precise
      monitoring of treatment response. Here we investigated a novel nanolock-nanopore
      method for single-molecule detection of a serine/threonine protein kinase gene
      BRAF V600E mutation in tumor tissues of thyroid cancer patients. The method lies
      in a noncovalent, mutation sequence-specific nanolock. We found that the nanolock
      formed on the mutant allele/probe duplex can separate the duplex dehybridization
      procedure into two sequential steps in the nanopore. Remarkably, this stepwise
      unzipping kinetics can produce a unique nanopore electric marker, with which a
      single DNA molecule of the cancer mutant allele can be unmistakably identified in
      various backgrounds of the normal wild-type allele. The single-molecule
      sensitivity for mutant allele enables both binary diagnostics and quantitative
      analysis of mutation occurrence. In the current configuration, the method can
      detect the BRAF V600E mutant DNA lower than 1% in the tumor tissues. The nanolock
      nanopore method can be adapted to detect a broad spectrum of both transversion
      and transition DNA mutations, with applications from diagnostics to targeted
      therapy.

PMID- 28750525
TI  - Wireless Passive Stimulation of Engineered Cardiac Tissues.
AB  - We present a battery-free radio frequency (RF) microwave activated wireless
      stimulator, 25 * 42 * 1.6 mm3 on a flexible substrate, featuring high current
      delivery, up to 60 mA, to stimulate engineered cardiac tissues. An external
      antenna shines 2.4 GHz microwave, which is modulated by an inverted pulse to
      directly control the stimulating waveform, to the wireless passive stimulator.
      The stimulator is equipped with an on-board antenna, multistage diode
      multipliers, and a control transistor. Rat cardiomyocytes, seeded on electrically
      conductive gelatin-based hydrogels, demonstrate synchronous contractions and Ca2+
      transients immediately upon stimulation. Notably, the stimulator output voltage
      and current profiles match the tissue contraction frequency within 0.5-2 Hz.
      Overall, our results indicate the promising potential of the proposed wireless
      passive stimulator for cardiac stimulation and therapy by induction of precisely
      controlled and synchronous contractions.

PMID- 28750526
TI  - Improved Sensitivity of Acetaldehyde Biosensor by Detecting ADH Reverse Reaction
      Mediated NADH Fluoro-Quenching for Wine Evaluation.
AB  - Acetaldehyde (AcH) is found in ambient air, foods, and the living body. This
      toxic substance is also contained in wine and known as an important ingredient
      affecting the quality of wine. Herein, we constructed and evaluated two different
      fiber-optic biosensors for measurement of AcH in the liquid phase (AcH biosensor)
      using aldehyde dehydrogenase (ALDH) or alcohol dehydrogenase (ADH). The AcH
      biosensor measured a concentration of AcH using fluorescence intensity of a
      reduced form of nicotinamide adenine dinucleotide (NADH) that was produced or
      consumed via catalytic reaction of the respective enzyme. In the AcH measurement
      system, an ultraviolet light emitting diode (UV-LED) and photomultiplier tube
      (PMT) were connected to a bifurcated optical fiber and were used to excite and
      detect NADH. A sensing region was developed using an optical fiber probe and an
      enzyme-immobilized membrane, buffer pH, and concentrations of a coenzyme in
      buffer solution for ALDH forward reaction and ADH reverse reaction were
      optimized, and the dynamic ranges were compared. ADH-mediated AcH biosensor
      showed higher sensitivity, wider dynamic range (1-500 MUM), and capability of
      rapid measurement (less than 3 min) than ALDH-mediated AcH biosensor (5-200 MUM).
      ADH biosensor also presented a high selectivity and allowed measurement of AcH in
      9 different wine samples (5 red and 4 white wines). The determined concentrations
      were comparable to those measured by NADH absorbance method, which validated the
      accuracy of the ADH biosensor in AcH measurement.

PMID- 28750527
TI  - Novel Biomimic Crystalline Colloidal Array for Fast Detection of Trace Parathion.
AB  - A novel gold doped inverse opal photonic crystal (IO PC) was successfully
      fabricated with combination of molecularly imprinted technical for the fast
      determination of parathion. First, a closest silica array arrangement behaved as
      the 3D photonic crystal precursors to build the opal photonic crystal (O PC).
      Second, the parathion-containing polymeric solution with gold nanoparticles was
      drawn into the 3D array cracks. After polymerization, the well-designed O PC was
      treated with HF solution for the etching of the silica skeleton. Finally, the
      template parathion was removed and the Au-MIP IO PCs were obtained. The
      morphology of SiO2 and Au NPs was characterized by transmission electron
      microscopy (TEM), and the eluted influence of the IO PCs was monitored by
      scanning electron microscopy (SEM). The cross-linking effect was well optimized
      according to the best spectrum signal of parathion. The as-synthesized Au-MIP IO
      PCs displayed the specificity toward parathion and the selectivity to other
      competitive pesticide molecules. The response time was only 5 min, and the
      parathion could be well detected from real water samples. The recoveries were
      between 95.5% and 101.5%.

PMID- 28750528
TI  - Plasmon-Based Colorimetric Nanosensors for Ultrasensitive Molecular Diagnostics.
AB  - Colorimetric detection of target analytes with high specificity and sensitivity
      is of fundamental importance to clinical and personalized point-of-care
      diagnostics. Because of their extraordinary optical properties, plasmonic
      nanomaterials have been introduced into colorimetric sensing systems, which
      provide significantly improved sensitivity in various biosensing applications.
      Here we review the recent progress on these plasmonic nanoparticles-based
      colorimetric nanosensors for ultrasensitive molecular diagnostics. According to
      their different colorimetric signal generation mechanisms, these plasmonic
      nanosensors are classified into two categories: (1) interparticle distance
      dependent colorimetric assay based on target-induced forming cross-linking
      assembly/aggregate of plasmonic nanoparticles; and (2) size/morphology-dependent
      colorimetric assay by target-controlled growth/etching of the plasmonic
      nanoparticles. The sensing fundamentals and cutting-edge applications will be
      provided for each of them, particularly focusing on signal generation and/or
      amplification mechanisms that realize ultrasensitive molecular detection.
      Finally, we also discuss the challenge and give our future perspective in this
      emerging field.

PMID- 28750529
TI  - Trace Analysis and Chemical Identification on Cellulose Nanofibers-Textured SERS
      Substrates Using the "Coffee Ring" Effect.
AB  - Surface-enhanced Raman scattering (SERS) has the theoretical possibility of
      detecting chemicals at the single molecular level. This potential is frequently
      limited, however, by the critical requirements of the surface morphology and
      mechanical stability of SERS substrates. In this paper, we report a new method
      for fabricating a SERS substrate with a significantly improved mechanical
      stability and analytical sensitivity, using cellulose nanofibers (CNFs) and gold
      nanoparticles (AuNPs). We constructed a uniformly CNFs-textured substrate on a
      glass surface by means of suppressing the "coffee ring" effect of the CNF sessile
      drop and then introduced an AuNP suspension onto the CNFs-textured substrate by
      taking advantage of the "coffee ring" effect. A widened detection zone is formed
      by AuNPs on the CNFs-textured glass, producing a stable SERS substrate for trace
      analysis and chemical identification. Microscopic and spectroscopic
      characterizations of the CNF-AuNPs SERS substrate show that the CNFs enhance the
      stability of both the AuNP clusters and the SERS activity. The CNF-AuNPs SERS
      substrate is significantly more stable and sensitive than the SERS substrate
      fabricated by directly depositing the AuNP suspension on a smooth glass surface.

PMID- 28750530
TI  - Wireless Oxygen Sensors Enabled by Fe(II)-Polymer Wrapped Carbon Nanotubes.
AB  - Oxygen causes food spoilage and drug degradation, which is addressed commercially
      by modified atmosphere packaging. We report herein a wireless oxygen sensor, O2-p
      CARD, from solution processed FeII-poly(4-vinylpyridine)-single-walled carbon
      nanotube composites on commercial passive near-field communication tags. A large
      irreversible attenuation in the reflection signal of an O2-p-CARD was observed in
      response to oxygen at relevant concentrations, enabling non-line-of-sight
      monitoring of modified atmosphere packaging. These devices allow for cumulative
      oxygen exposure inside a package to be read with a conventional smartphone. We
      have demonstrated that an O2-p-CARD can detect air ingress into a nitrogen-filled
      vegetable package at ambient conditions. This technology provides an inexpensive,
      heavy-metal-free, and smartphone-readable method for in situ non-line-of-sight
      quality monitoring of oxygen-sensitive packaged products.

PMID- 28750531
TI  - Electrostatic Cycling of Hybridization Using Nonionic DNA Mimics.
AB  - This study demonstrates efficient electrostatic control of surface hybridization
      through use of morpholinos, a charge-neutral DNA mimic, as the immobilized
      "probes". In addition to being compatible with low ionic strengths, use of
      uncharged probes renders the field interaction specific to the nucleic acid
      analyte. In contrast to DNA probes, morpholino probes enable facile cycling
      between hybridized and dehybridized states within minutes. Impact of ionic
      strength and temperature on the effectiveness of electrostatics to direct
      progress of hybridization is evaluated. Optimal electrostatic control is found
      when stability of probe-analyte duplexes is set so that electrostatics can
      efficiently switch between the forward (hybridization) and reverse
      (dehybridization) directions.

PMID- 28750532
TI  - Tracking Lithium Ions via Widefield Fluorescence Microscopy for Battery
      Diagnostics.
AB  - Direct tracking of lithium ions with time and spatial resolution can provide an
      important diagnostic tool for understanding mechanisms in lithium ion batteries.
      A fluorescent indicator of lithium ions, 2-(2-hydroxyphenyl)naphthoxazole, was
      synthesized and used for real-time tracking of lithium ions via widefield
      fluorescence microscopy. The fluorophore can be excited with visible light and
      was shown to enable quantitative determination of the lithium ion diffusion
      constant in a microfluidic model system for a plasticized polymer electrolyte
      lithium battery. The use of widefield fluorescence microscopy for in situ
      tracking of lithium ions in batteries is discussed.

PMID- 28750534
TI  - Functionalization-Free Microfluidic Electronic Tongue Based on a Single Response.
AB  - Electronic tongues (e-tongues) are promising analytical devices for a variety of
      applications to address the challenges of quality control in water monitoring and
      industries of foods, beverages, and pharmaceuticals. A crucial drawback in the
      current e-tongues is the need to recalibrate the device when one or more sensing
      units (usually with modified surface) are replaced. Another downside is the
      necessity to perform subsequent surface modifications and analyses to each of the
      diverse sensing units, undermining the simplicity and velocity of the method.
      These features have prevented widespread commercial use of the e-tongues. In this
      paper, we introduce a microfluidic e-tongue that overcomes all such limitations.
      The key principle of global selectivity of the e-tongue was achieved by recording
      only a single response, namely, the equivalent admittance spectrum of an
      association of resistors in parallel. Such resistors consisted of five
      nonfunctionalized stainless steel microwires (sensing units), which were short
      circuited and coated with gold, platinum, nickel, iron, and aluminum oxide films.
      The microwires were inserted in a chip composed of a single piece of
      polydimethylsiloxane (PDMS). Using impedance spectroscopy, the e-tongue was
      successfully applied in classification of basic tastes at a concentration below
      the threshold for the human tongue. In addition, our chip allowed the distinction
      of various chemicals used in oil industry. Finally, our cleanroom-free
      prototyping allows the mass production of chips with easily replaceable and
      reproducible sensing units. Hence, one can now envisage the widespread
      dissemination of e-tongues with fast and reproducible data.

PMID- 28750535
TI  - Evaluation of DNA Methyltransferase Activity and Inhibition via Isothermal Enzyme
      Free Concatenated Hybridization Chain Reaction.
AB  - Methyltransferase (MTase)-catalyzed DNA methylation plays a vital role in the
      biological epigenetic processes of key diseases and has attracted increasing
      attention, making the amplified detection of MTase activity of great significance
      in clinical disease diagnosis and treatment. Herein, we developed an isothermal,
      enzyme-free, and autonomous strategy for analyzing MTase activity based on
      concatenated hybridization chain reaction (C-HCR)-mediated Forster resonance
      energy transfer (FRET). In a typical C-HCR procedure without MTase (Dam), Y
      shaped initiator DNA activates upstream HCR-1 to assemble a double-stranded DNA
      (dsDNA) copolymeric nanowire consisting of multiple tandem DNA trigger units that
      motivate downstream HCR-2 to successively bring a fluorophore donor/acceptor
      (FAM/TAMRA) pair into close proximity, leading to the generation of an amplified
      FRET readout signal. The target Dam MTase and auxiliary DpnI endonuclease can
      sequentially and specifically recognize/methylate and cleave the Y-shaped
      initiator oligonucleotide, respectively, and thus prohibit the C-HCR process and
      FRET signal generation, resulting in the construction of a signal-on sensing
      platform for MTase assay. Our proposed isothermal enzyme-free C-HCR amplification
      approach was further utilized for screening MTase inhibitors. Furthermore, the
      proposed C-HCR approach can be easily adapted for probing other different MTases
      and for screening the corresponding inhibitors just by changing the recognition
      sequence of Y-shaped initiator DNA through a "plug-and-play" format. It provides
      a versatile and robust tool for highly sensitive detection of various
      biotransformations and thus holds great promise in clinical assessment and
      diagnosis.

PMID- 28750536
TI  - Magnetite-Quantum Dot Immunoarray for Plasmon-Coupled-Fluorescence Imaging of
      Blood Insulin and Glycated Hemoglobin.
AB  - New microarray chip strategies that are sensitive and selective and that can
      measure low levels of important biomarkers directly in a blood sample are
      significant for improving human health by allowing timely diagnosis of an
      abnormal condition. Herein, we designed an antibody-aptamer immunoarray chip to
      demonstrate simultaneous measurement of blood insulin and glycated hemoglobin
      (HbA1c) levels relevant to diabetic and prediabetic disorders using a surface
      plasmon microarray with validation by fluorescence imaging. To accomplish both
      surface plasmon and fluorescence imaging on the same sample, we decorated
      magnetite nanoparticles with quantum dots for covalent immobilization of aptamers
      for subsequent capture and isolation of the aptamers specific for insulin and
      HbA1c markers from 20-times diluted whole blood samples. Direct clinically
      relevant analysis, along with fluorescent imaging of the two markers, was
      achieved by this new immunoarray platform. The limit of detection was 4 pM for
      insulin and 1% for HbA1c. Examination of cross-talk using thrombin and platelet
      derived growth factor confirmed that the designed immunoarray was highly
      selective for insulin and HbA1c. Surface plasmon kinetic analysis provided
      apparent binding constants of 0.24 (+/-0.08) nM and 37 (+/-3) MUM, respectively,
      for the binding of insulin and HbA1c onto their surface immobilized monoclonal
      antibodies. Thus, quantitative imaging of ultralow levels of blood biomarker
      levels with binding kinetics is uniquely obtained in the designed immunoarray
      chip. In conclusion, this report demonstrates considerable significance of the
      developed magnetite-quantum dot-bioconjugate strategy for clinical diagnostics of
      whole blood biomarkers with characterization of molecular binding interactions.

PMID- 28750537
TI  - Fluorescent Protein-Based Turn-On Probe through a General Protection-Deprotection
      Design Strategy.
AB  - We demonstrated a general protection-deprotection strategy for the design of
      fluorescent protein biosensors through the construction of a turn-on Hg2+ sensor.
      A combination of fluorescent protein engineering and unnatural amino acid
      mutagenesis was used. Unlike previously reported fluorescent protein-based Hg2+
      sensors that relied on the binding of Hg2+ to the sulfhydryl group of cysteine
      residues, a well-established chemical reaction, oxymercuration, was transformed
      into biological format and incorporated into our sensor design. This novel Hg2+
      sensor displayed good sensitivity and selectivity both in vitro and in live
      bacterial cells. Over 60-fold change in fluorescence signal output was observed
      in the presence of 10 MUM Hg2+, while such a change was undetectable when nine
      other metal ions were tested. This new design strategy could expand the
      repertoire of fluorescent protein-based biosensors for the detection of small
      molecule analytes.

PMID- 28750538
TI  - Two-Dimensional Zirconium-Based Metal-Organic Framework Nanosheet Composites
      Embedded with Au Nanoclusters: A Highly Sensitive Electrochemical Aptasensor
      toward Detecting Cocaine.
AB  - Two-dimensional (2D) zirconium-based metal-organic framework nanosheets embedded
      with Au nanoclusters (denoted as 2D AuNCs@521-MOF) were prepared via a one-pot
      method under mild conditions. The optimized 2D AuNCs@521-MOF nanosheets not only
      possessed high specific surface area, physicochemical stability, and good
      electrochemical activity but also exhibited strong bioaffinity toward biomolecule
      bearing phosphate groups. Consequently, a large amount of cocaine aptamer strands
      can be immobilized onto the substrate modified by 2D AuNCs@521-MOF nanosheet,
      further leading to the formation of a constructed biosensitive platform, which
      can be used to successfully detect cocaine through the specific binding
      interactions between cocaine and aptamer strands. The results demonstrated that
      the 2D AuNCs@521-MOF-based aptasensor had high sensitivity for detecting cocaine
      within the broad concentration range of 0.001-1.0 ng.mL-1 and the low limit of
      detection of 1.29 pM (0.44 pg.mL-1) and 2.22 pM (0.75 pg.mL-1) as determined by
      electrochemical impedance spectroscopy and differential pulse voltammetry,
      respectively. As expected, with the advantages of high selectivity,
      repeatability, stability, and simple operation, this new strategy is believed to
      exhibit great potential for simple and convenient detection of cocaine.

PMID- 28750539
TI  - Octupolar Metastructures for a Highly Sensitive, Rapid, and Reproducible Phage
      Based Detection of Bacterial Pathogens by Surface-Enhanced Raman Scattering.
AB  - The development of fast and ultrasensitive methods to detect bacterial pathogens
      at low concentrations is of high relevance for human and animal health care and
      diagnostics. In this context, surface-enhanced Raman scattering (SERS) offers the
      promise of a simplified, rapid, and high-sensitive detection of biomolecular
      interactions with several advantages over previous assay methodologies. In this
      work, we have conceived reproducible SERS nanosensors based on tailored
      multilayer octupolar nanostructures which can combine high enhancement factor and
      remarkable molecular selectivity. We show that coating novel multilayer octupolar
      metastructures with proper self-assembled monolayer (SAM) and immobilized phages
      can provide label-free analysis of pathogenic bacteria via SERS leading to a
      giant increase in SERS enhancement. The strong relative intensity changes of
      about 2100% at the maximum scattered SERS wavelength, induced by the Brucella
      bacterium captured, demonstrate the performance advantages of the bacteriophage
      sensing scheme. We performed measurements at the single-cell level thus allowing
      fast identification in less than an hour without any demanding sample preparation
      process. Our results based on designing well-controlled octupolar coupling
      platforms open up new opportunities toward the use of bacteriophages as
      recognition elements for the creation of SERS-based multifunctional biochips for
      rapid culture and label-free detection of bacteria.

PMID- 28750540
TI  - Electrochromic Sensor for Multiplex Detection of Metabolites Enabled by Closed
      Bipolar Electrode Coupling.
AB  - Biosensors based on converting electrochemical signals into optical readouts are
      attractive candidates as low-cost, high-throughput sensor platforms. Here, we
      described a closed bipolar electrode (CBE)-based two-cell electrochromic device
      for sensing multiple metabolites, using the simultaneous detection of lactate,
      glucose, and uric acid as a model system. In the two-cell configuration, an
      analytical cell contains a redox mediator combined with a specific oxidase, e.g.,
      lactate oxidase, glucose oxidase, or uricase, to form an electrochemical mediator
      electrocatalyst pair that supports redox cycling. A closed bipolar electrode
      couples the electron transfer event in the analytical cell to an electrochromic
      reaction in a separate reporter cell, such that the magnitude of the color change
      is related to the concentration of metabolites in the analytical cell. To
      demonstrate multiplex operation, the CBE-based electrochromic detector is
      modified by integrating three sets of detection chemistries into a single device,
      in which simultaneous determination of glucose, lactate, and uric acid is
      demonstrated. Device sensitivity can be tuned by using reporter cells with
      different volumes. Furthermore, the analytical cell of this device can be
      fabricated as a disposable, paper-based carbon electrode without any
      pretreatment, demonstrating the potential to screen phenotypes that require
      multiple biomarkers in a point-of-care format.

PMID- 28750541
TI  - Influence of different cleaning processes on the surface chemistry of gold
      nanoparticles.
AB  - In this paper, the authors have investigated the effects of different cleaning
      methods (centrifugation and dialysis) on the surface chemistry and composition of
      15 nm sodium citrate stabilized gold nanoparticles. The nuclear magnetic
      resonance (NMR) results indicate that three centrifugation cycles are sufficient
      to remove most of the citrate molecules, while centrifuged liquid sedimentation
      and dynamic light scattering data reveal some degree of nanoparticle aggregation
      when three centrifugation cycles are exceeded. Regarding the dialysis procedure,
      NMR analysis demonstrated that after nine cleaning cycles, the citrate
      concentration is comparable to that measured after the first centrifugation
      (about 6 * 10-4 M) but with an increase in the dispersion polydispersivity index
      as determined by dynamic light scattering. X-ray photoelectron spectroscopy
      results support the NMR findings and revealed a major hydrocarbon contamination
      after the nanoparticles cleaning process. The impact of cleaning on surface
      functionalization was tested using 1H,1H,2H,2H-perfluorodecanethiol hydrophobic
      thiols (PFT) to test thiol-citrate substitution. After 24 h exposure, the PFT
      coverage was less than 0.6 monolayer (ML) for both pristine nanoparticles and
      particles after three dialysis cycles, but about 0.8 ML after two centrifugation
      washes.

PMID- 28750542
TI  - Clinical Presentation, Predictors, and Outcomes Among Mineralocorticoid Receptor
      Antagonist (MRA)-Eligible Acute Heart Failure Patients in the Heart Function
      Assessment Registry Trial in Saudi Arabia (HEARTS).
AB  - Mineralocorticoid receptor antagonist (MRA) therapy is indicated after myocardial
      infarction in patients with acute heart failure (AHF) with an ejection fraction
      <=40% and lacking contraindications. We analyzed clinical presentations,
      predictors, and outcomes of MRA-eligible patients within a prospective registry
      of patients with AHF from 18 hospitals in Saudi Arabia, from 2009 to 2010. For
      this subgroup, mortality rates were followed until 2013, and the clinical
      characteristics, management, predictors, and outcomes were compared between MRA
      treated and non-MRA-treated patients. Of 2609 patients with AHF, 387 (14.8%) were
      MRA eligible, of which 146 (37.7%) were prescribed MRAs. Compared with non-MRA
      treated patients, those prescribed MRAs more commonly exhibited non-ST-segment
      elevation myocardial infarction, acute on chronic heart failure, past history of
      ischemic heart disease, and severe left ventricular systolic dysfunction; were
      more commonly administered oral furosemide and digoxin; and had higher in
      hospital recurrent congestive HF rates. Mortality did not significantly differ (
      P > .05) between groups. In Saudi Arabia, 37.7% of eligible patients received MRA
      treatment, which is higher than that in developed countries. The lack of long
      term survival benefit raises concerns about systematic problems, for example,
      proper follow-up and management after hospital discharge, warranting further
      investigation.

PMID- 28750543
TI  - Bio-ecological factors associated with the psychological distress of fathers of
      children with autism spectrum disorder: A population-based study of Australian
      families.
AB  - Using a bio-ecological framework, the aim of this study was to examine factors
      associated with psychological distress experienced by fathers of children with
      autism spectrum disorder from a nationally representative sample of Australian
      children and their families. Individual (e.g. age and self-efficacy),
      interpersonal (e.g. partner distress, couple relationship, child behaviour and
      social support) and social environmental factors (e.g. job quality and financial
      hardship) were explored as potential predictors of fathers' distress. Data were
      drawn from the Longitudinal Study of Australian Children, where 159 fathers of
      children with autism spectrum disorder were identified. As comparison, 6578
      fathers of children without developmental disabilities were identified. Multiple
      regression analyses showed that experiencing depression within the past year, job
      quality (e.g. autonomy and access to parental leave) and social support were
      significant predictors for fathers of children with autism spectrum disorder. The
      importance of supporting the well-being of fathers of children with autism
      spectrum disorder is discussed.

PMID- 28750544
TI  - Emotion awareness and cognitive behavioural therapy in young people with autism
      spectrum disorder.
AB  - Young people with autism spectrum disorder experience high levels of emotional
      problems, including anxiety and depression. Adapted cognitive behavioural therapy
      is recommended for such difficulties. However, no evidence suggests whether
      emotion awareness is important in treatment outcome for young people on the
      autism spectrum. This study aimed to investigate the potential differences in
      emotion awareness between (1) young people on the autism spectrum and typically
      developing youth and (2) young people on the autism spectrum with and without
      experience of cognitive behavioural therapy. Three groups (aged 11-20 years)
      participated: (1) typically developing young people ( n = 56); (2) young people
      on the autism spectrum with no experience of cognitive behavioural therapy ( n =
      23); and (3) young people on the autism spectrum who had attended cognitive
      behavioural therapy ( n = 33). All participants completed the Emotion Awareness
      Questionnaire-30 item version. Young people on the autism spectrum differed
      significantly from typically developing young people on the emotional awareness
      measure. Young people on the autism spectrum who had attended cognitive
      behavioural therapy scored significantly lower on the Differentiating Emotions
      subscale, and significantly higher on the Attending to Others' Emotions subscale,
      compared to young people on the autism spectrum who had not attended cognitive
      behavioural therapy. This study highlights the importance of psycho-educational
      components of cognitive behavioural therapy when adapting for young people on the
      autism spectrum.

PMID- 28750545
TI  - Contribution of individual flavonoids in Lysimachia species to the antioxidant
      capacity based on HPLC-DPPH assay.
AB  - Quantitative phytochemical characterisation of the chief flavonoid aglycones in
      the hydrolysed Lysimachia extracts revealed the dominance of kaempferol,
      quercetin and myricetin in L. vulgaris, L. nummularia, L. punctata, L.
      christinae, L. ciliata and L. clethroides, respectively. Due to the significant
      radical scavenging capacity of the samples, the contribution of the individual
      aglycones to the total antioxidant activity became of interest. Therefore, a HPLC
      method coupled to pre-column DPPH scavenging assay was developed. Differences in
      the six Lysimachia species' phenolic composition regarding their participation to
      the antioxidant activity were revealed. The participation of the three
      investigated flavonoids to the radical quenching activity was the highest (91.2%)
      in the L. vulgaris sample, the lowest in L. christinae sample with 29.6%. In L.
      vulgaris sample, the 76.3% contribution of quercetin to the scavenger capacity
      was the highest peak area decrement ratio among the investigated samples.

PMID- 28750546
TI  - Factors associated with the quality of life of people with dementia and with
      quality of life-improving interventions: Scoping review.
AB  - : Objectives To synthesise current research exploring the factors and
      interventions associated with the quality of life of people with dementia.
      Background Dementia is a progressive condition affecting an estimated 40 million
      people worldwide. The illness has a significant impact on the lives of the
      persons affected and their loved ones, and may thus impair the quality of life of
      both. As it progresses, dementia weakens the patients' ability to express their
      own views about their quality of life and the factors associated with it. Design
      Scoping review. Data sources Electronic database search of MEDLINE, CINAHL,
      PsycINFO, Joanna Briggs Institute Library, Cochrane Database of Systematic
      Reviews, Database of Abstracts of Reviews of Effects (DARE), EMBASE, Medic
      published up to March 2016; and incremental hand search. REVIEW METHOD:
      Systematic or other kinds of reviews and single studies were included for the
      review if they met the inclusion criteria. RESULTS: A total of 20 reviews and 7
      primary studies were retained for synthesis. Key findings were abstracted and a
      themes matrix was generated to identify patterns of meaning. The factors
      associated with the quality of life of people with dementia were sociodemographic
      factors, factors related to dementia and social and caring environment.
      Interventions supporting quality of life focused on the activation of people with
      dementia. CONCLUSIONS: This scoping review identified a large body of knowledge
      exploring the factors and interventions associated with the quality of life of
      people with dementia. The interventions were heterogeneous and the sample sizes
      small, which is why more research is needed.

PMID- 28750547
TI  - Addressing medical needs of adolescents and adults with autism spectrum disorders
      in a primary care setting.
AB  - Little has been reported about how to improve health care access and delivery for
      adolescents and adults with autism spectrum disorder. To understand the
      contributions to the health disparities in the autism spectrum disorder
      population, we conducted two independent research approaches to learn about
      current medical needs. A retrospective chart review was performed to evaluate
      medical comorbidities and medication use. A focus group was also created to
      address barriers faced in providing medical care. Of 126 charts reviewed, 49% (n
      = 62) had intellectual disability, 49% (n = 62) had attention-deficit
      hyperactivity disorder, 52% (n = 65) had anxiety, 41% (n = 52) had obesity, 31%
      (n = 39) with a history of aggressive behavior, 31% (n = 31) had depression, 22%
      (n = 28) had seizures, and 9% (n = 11) had hypertension. A Medical Regimen
      Complexity Index score was determined to examine medication use trends in the
      autism spectrum disorder population. Medical Regimen Complexity Index scores were
      significantly higher for patients with intellectual disability, patients with
      seizures, and patients with a history of aggressive behavior. Both the focus
      group and our pre-visit assessment identified the waiting room and waiting time
      as barriers to care. Understanding the comorbidities, polypharmacy, and medical
      barriers should provide a better understanding of the current health care access
      and delivery needs of adolescents and adults with autism spectrum disorder.

PMID- 28750548
TI  - A feasibility study of a novel, task-specific movement training intervention for
      women with patellofemoral pain.
AB  - OBJECTIVE: To investigate whether a novel, task-specific training intervention
      that focused on correcting pain-producing movement patterns was feasible and
      whether it would improve hip and knee kinematics, pain, and function in women
      with patellofemoral pain. DESIGN: Prospective, non-randomized, within-group,
      double baseline, feasibility intervention study. SUBJECTS: A total of 25 women
      with patellofemoral pain were enrolled. INTERVENTION: The intervention, delivered
      2*/week for six weeks, consisted of supervised, high-repetition practice of daily
      weight-bearing and recreational activities. Activities were selected and
      progressed based on participants' interest and ability to maintain optimal
      alignment without increasing pain. MAIN MEASURES: Primary feasibility outcomes
      were recruitment, retention, adherence, and treatment credibility
      (Credibility/Expectancy Questionnaire). Secondary outcomes assessing intervention
      effects were hip and knee kinematics, pain (visual analog scale: current, average
      in past week, maximum in past week), and function (Patient-Specific Functional
      Scale). RESULTS: A total of 25 participants were recruited and 23 were retained
      (92% retention). Self-reported average daily adherence was 79% and participants
      were able to perform their prescribed home program correctly (reduced hip and
      knee frontal plane angles) by the second intervention visit. On average,
      treatment credibility was rated 25 (out of 27) and expectancy was rated 22 (out
      of 27). Hip and knee kinematics, pain, and function improved following the
      intervention when compared to the control phase. CONCLUSION: Based on the
      feasibility outcomes and preliminary intervention effects, this task-specific
      training intervention warrants further investigation and should be evaluated in a
      larger, randomized clinical trial.

PMID- 28750549
TI  - The role of movement errors in modifying spatiotemporal gait asymmetry post
      stroke: a randomized controlled trial.
AB  - OBJECTIVE: Current rehabilitation to improve gait symmetry following stroke is
      based on one of two competing motor learning strategies: minimizing or augmenting
      symmetry errors. We sought to determine which of those motor learning strategies
      best improves overground spatiotemporal gait symmetry. DESIGN: Randomized
      controlled trial. SETTING: Rehabilitation research lab. SUBJECTS: In all, 47
      participants (59 +/- 12 years old) with chronic hemiparesis post stroke and
      spatiotemporal gait asymmetry were randomized to error augmentation, error
      minimization, or conventional treadmill training (control) groups. INTERVENTIONS:
      To augment or minimize asymmetry on a step-by-step basis, we developed a
      responsive, "closed-loop" control system, using a split-belt instrumented
      treadmill that continuously adjusted the difference in belt speeds to be
      proportional to the patient's current asymmetry. MAIN MEASURES: Overground
      spatiotemporal asymmetries and gait speeds were collected prior to and following
      18 training sessions. RESULTS: Step length asymmetry reduced after training, but
      stance time did not. There was no group * time interaction. Gait speed improved
      after training, but was not affected by type of asymmetry, or group. Of those who
      trained to modify step length asymmetry, there was a moderately strong linear
      relationship between the change in step length asymmetry and the change in gait
      speed. CONCLUSION: Augmenting errors was not superior to minimizing errors or
      providing only verbal feedback during conventional treadmill walking. Therefore,
      the use of verbal feedback to target spatiotemporal asymmetry, which was common
      to all participants, appears to be sufficient to reduce step length asymmetry.
      Alterations in stance time asymmetry were not elicited in any group.

PMID- 28750550
TI  - Increasing HPV Vaccination Coverage Through Provider-Based Interventions.
AB  - With discouragingly low vaccination rates for human papillomavirus (HPV), we
      sought to improve the HPV vaccine completion rate for adolescents by increasing
      the consistency and quality of provider recommendations. Baseline data was
      extracted for vaccine completion rates among patients aged 13 to 17 years.
      Quality improvement measures led to interventions targeting factors associated
      with vaccine noncompletion, in particular, weaknesses in provider recommendations
      and patient characteristics most strongly correlated with missed vaccination
      opportunities. Vaccine completion rates increased overall from 50.9% to 61.7% ( P
      < .05), an increase seen in both males (42.6% to 57.3%, P < .001) and females
      (60.0% to 66.5%, P = .04). One-dose rates improved to 88.4% for males ( P = .02)
      and 91.5% for females ( P = .43). Vaccination also occurred more consistently,
      increasing from 77.5% of visits (95% CI 71.2-83.0) before study onset to 90.9% of
      visits (95% CI 85.4%-94.8%) afterward ( P < .01). HPV vaccination rates can
      increase through focused provider-level prompts and by offering the vaccine
      consistently.

PMID- 28750551
TI  - Midterm Results of the Salto Talaris Total Ankle Arthroplasty.
AB  - BACKGROUND: The Salto Talaris total ankle replacement is a modern fixed-bearing
      implant used to treat symptomatic ankle arthritis with the goals of providing
      pain relief, restoring mechanical alignment, and allowing motion of the ankle
      joint. The goal of this study was to report the midterm clinical results of one
      of the largest cohort of patients in the United States who underwent ankle
      replacement with this prosthesis. METHODS: This is a review of patients with a
      minimum of 5 years up to 10 years' follow-up. At the preoperative visit and each
      annual assessment, patients rated their current level of pain using the visual
      analog score (VAS) and reported their functional level using the American
      Orthopaedic Foot & Ankle (AOFAS) ankle-hindfoot scores, the Short Musculoskeletal
      Function Assessment (SMFA), and the Short Form-36 (SF-36) Health survey. These
      scores were analyzed to assess differences between their levels preoperatively, 1
      year postoperatively, and at their most recent follow-up. Criteria for failure
      was defined as revision requiring exchange or removal of the metallic components
      for any reason. We identified 106 patients having a Salto Talaris total ankle
      replacement. Seventy-two patients (mean age, 61.9 years) met the minimum
      requirement for follow-up (range 60-115 months, mean 81.1 months). RESULTS:
      Significant improvements were seen in the VAS, SMFA, AOFAS score, and SF-36 from
      preoperatively to their final follow-up ( P < .001). Survivorship was 95.8% for
      those with at least 5-year follow-up, with 2 patients undergoing revision
      arthroplasty for aseptic loosening and a third patient scheduled for revision for
      a chronic wound infection. Fourteen patients (19%) required an additional surgery
      for a total of 17 additional operative procedures on the ipsilateral ankle or
      hindfoot. CONCLUSION: Patients undergoing total ankle arthroplasty with the Salto
      Talaris prosthesis continued to show significant improvements in pain and
      functional outcomes at midterm follow-up. This prosthesis has shown to be an
      effective treatment option with durable results. LEVEL OF EVIDENCE: Level IV,
      therapeutic, case series.

PMID- 28750552
TI  - Human skin gene expression: Natural (trans) resveratrol versus five resveratrol
      analogs for dermal applications.
AB  - Resveratrol (RV) is a polyphenolic compound naturally produced by plants.
      Polyphenolic compounds incorporated into medicinal products are beneficial but,
      RV is rapidly metabolized with an associated decline in biological activity. This
      study tested RV as the standard and compared five structurally modified RV
      analogs: butyrate, isobutyrate, palmitoate, acetate, and diacetate (to improve
      functionality) at 1% concentration(s) for 24 h in epiderm full thickness cultures
      by gene array/qPCR mRNA analysis. When silent mating type information regulation
      2 homolog 1, extracellular elements (collagen1A1, 3A1, 4A1; elastin, tissue
      inhibitor of matrix metalloproteinase 1, fibrillin 1 laminin beta1 and matrix
      metalloproteinase 9), anti-aging and aging genes, inflammatory biomarkers
      (interleukin-1A [IL1A], IL1R2, IL-6 and IL-8), nerve growth factor, and the
      antioxidants (proliferating cell nuclear antigen, catalase, superoxide dismutase
      and metallothionein 1H/2H) were evaluated, ranking each from highest-to-lowest
      for gene expression: butyrate > isobutyrate > diacetate > acetate > palmitoate.
      This study showed that the butyrate and isobutyrate analogs are more biologically
      active compared to resveratrol and have potential use in topical applications to
      improve dermal and other health applications. Impact statement Resveratrol has
      been reported to have a wide variety of health benefits but its rapid metabolism
      especially after oral ingestion results in very low bioavailability. Notably, the
      first human skin gene expression study of resveratrol was not published until
      2014. The purpose of this study was to determine if increased stability and
      biological activity could be obtained by modifying the chemical structure of
      natural (trans) resveratrol and quantifying human gene expression by qPCR of skin
      biomarkers that enhance dermal health. Five resveratrol analogs were synthesized
      that increased their lipophilic index to enhance tissue penetration and augment
      biological activities on the measured parameters that expand the current
      knowledge of structure/function relationships. The butyrate and isobutyrate
      modifications displayed gene expression values significantly above resveratrol
      and suggest that oral application of these and potentially other resveratrol
      analogs may yield similar results to improve stability and biological activity to
      benefit/address various disorders/diseases.

PMID- 28750553
TI  - The Analgesic and Anti-Inflammatory Activity of Linum usitatissimum in Balb/c
      Mice.
AB  - Linum usitatissimum L is traditionally used for relief of pain and inflammation.
      In this study, the analgesic and anti-inflammatory effects of this plant were
      evaluated. Xylene test was used for anti-inflammatory evaluation in which 48 mice
      were randomly designated into 6 groups of 8 each including: control,
      dexamethasone as positive control (15 mg/kg), and experimental groups (42, 85,
      170, and 340 mg/kg, respectively). For analgesic evaluation, 192 mice were
      randomly designated into 4 sets of 6 groups of 8 mice, including control,
      morphine as positive control, morphine plus naloxone, experimental groups (200
      and 500 mg/kg extract), and extract along with naloxone group, which received 500
      mg/kg. The analgesic activities were evaluated at 5, 15, 30, and 60 minutes,
      respectively, in each set. Both doses showed analgesic activity, the 200 mg/kg
      possessed higher effects ( P < .05). Naloxone reduced a section of its effect ( P
      < .001). The 170 mg/kg dose of the extract showed anti-inflammatory activity ( P
      < .05). The extract had phenolic, flavonoid, and flavonol compounds with
      antioxidant activity. Linum usitatissimum L dose dependently had analgesic
      activity partially like morphine and might be used as analgesic and anti
      inflammatory agent.

PMID- 28750554
TI  - The TMA-93: A New Memory Test for Alzheimer's Disease in Illiterate and Less
      Educated People.
AB  - The present study aimed at validating the Memory Associative Test of the district
      of Seine-Saint-Denis (TMA)-93, a new test of episodic memory. The TMA-93 was
      proposed to mostly less educated and multicultural elderly population composed of
      376 healthy controls (HC) and 94 patients with Alzheimer's disease (AD). The
      construct validity was checked by studying correlations with a widely used memory
      test (the Free and Cued Selective Reminding Test [FCSRT]) in the subsample of
      literate patients. Results showed that (i) all the TMA-93 scores of the patients
      with AD were lower than those of the HC, (ii) the TMA-93 total score identified
      patients with AD with a high sensitivity (88%) and very high specificity (97%),
      and (iii) the TMA-93 total score was strongly correlated with both free recall
      and total recall scores of the FCSRT. Taken together, results showed that the TMA
      93 is a reliable tool to assess episodic memory in a multicultural, less
      educated, or illiterate population, with good construct validity for AD
      diagnostic accuracy.

PMID- 28750555
TI  - Achieving Improved Outcomes Through Value-Based Purchasing in One State.
AB  - Beginning as early as 2009, Texas began to put the antecedents in place for an
      effective Medicaid value-based purchasing model. Since those early activities
      were undertaken, Texas Medicaid is emerging as a national leader in value-based
      purchasing and has produced exceptional results that clearly demonstrate the
      value proposition associated with alignment of financial incentives. This article
      presents several years of data and preliminary results of this effort. This study
      found significant improvements in a number of outcomes. Further improvement will
      depend on implementation of financial incentives and ongoing commitment to paying
      for better outcomes. This ongoing commitment includes many additional programs
      that hospitals, in particular, have put in place such as improved handwashing
      techniques.

PMID- 28750556
TI  - The Quebec Respiratory Health Education Network: Integrating a model of self
      management education in COPD primary care.
AB  - The objective of this study is to evaluate whether a chronic obstructive
      pulmonary disease (COPD) self-management education program with coaching of a
      case manager improves patient-related outcomes and leads to practice changes in
      primary care. COPD patients from six family medicine clinics (FMCs) participated
      in a 1-year educational program offered by trained case managers who focused on
      treatment adherence, inhaler techniques, smoking cessation, and the use of an
      action plan for exacerbations. Health-care utilization, health-related quality of
      life (HRQL), treatment adherence, inhaler technique, and COPD knowledge were
      assessed at each visit with validated questionnaires. We also evaluated whether
      the use of spirometry and the assessment of individual patient needs led to a
      more COPD-targeted treatment by primary care physicians, based on changes in
      prescriptions for COPD (medication, immunization, and written action plan). Fifty
      four patients completed the follow-up visits and were included in the analysis.
      The number of unscheduled physician visits went from 40 the year before
      intervention to 17 after 1 year of educational intervention ( p = 0.033).
      Emergency room visits went from five to two and hospitalizations from two to
      three (NS). Significant improvements were observed in HRQL ( p = 0.0001),
      treatment adherence ( p = 0.025), adequate inhaler technique ( p < 0.0001), and
      COPD knowledge ( p < 0.001). Primary care physicians increased their
      prescriptions for long-acting bronchodilators with/without inhaled
      corticosteroid, flu immunizations, and COPD action plans in the event patient had
      an exacerbation. The COPD self-management educational intervention in FMCs
      reduced unscheduled visits to the clinic and improved patients' quality of life,
      self-management skills, and knowledge. The program had a positive impact on COPD
      related practices by primary care physicians in the FMCs.

PMID- 28750557
TI  - Qualitative and quantitative analysis of chemical constituents of Ptychopetalum
      olacoides Benth.
AB  - Ptychopetalum olacoides is a folk medicinal plant for health care in market,
      especially in Brazil. Fourteen known compounds were isolated from P. olacoides
      and their chemical structures were elucidated by extensive spectroscopic data,
      including 1D NMR, 2D NMR, UV, IR and HR-ESI-MS. The 14 known compounds were
      identified as N-trans-feruloyl-3,5-dihydroxyindolin-2-one (1), magnoflorine (2),
      menisperine (3), 4-coumaroylserotonin (4), moschamine (5), luteolin (6), 4'
      methoxyluteolin (7), 3-methoxyluteolin (8), 3, 7-dimethoxyluteolin (9), caffeic
      acid (10), ferulic acid (11), vanillic acid (12), syringic acid (13) and
      ginsenoside Re (14). To our knowledge, compounds (1-6, 13-14) were isolated from
      the plant for the first time. Additionally, quantitative analysis results
      indicated that calibration equations of compounds (1-3, 6, 9, 11-13) exhibited
      good linear regressions within the test ranges (R2 >= 0.9990) and magnoflorine
      and menisperine were the major constituents in the barks of P. olacoides. The
      contents of magnoflorine and menisperine accounted for 75.96% of all analytes.
      However, the content of phenolic components was smaller and the highest content
      was no more than 1.04 mg/g. Collectively, these results suggested that alkaloids
      are the dominant substances in P. olacoides, which can make a difference for the
      quality control and further use of P. olacoides.

PMID- 28750558
TI  - Case Report: Diagnosis of a Rare Plaque-Like Dermal Fibroma Successfully Treated
      With Mohs Surgery.
AB  - BACKGROUND: CD34-positive plaque-like dermal fibroma (PDF) is a poorly
      characterised benign dermal neoplasm that has a wide differential diagnosis. It
      can be mistaken for other entities on superficial biopsy and be overtreated,
      leading to unnecessary worry and extensive surgery. OBJECTIVE: To report on an
      uncommon presentation of this entity, the histopathologic differential diagnosis
      of PDF, and a novel treatment method. METHODS: Clinical and histopathological
      information was obtained for a PDF lesion on a 75-year-old man. RESULTS: On
      superficial biopsy, the PDF lesion was misinterpreted as a possible
      neurothekeoma. Successful Mohs surgery and genetic testing confirmed the
      diagnosis of PDF, and the patient received appropriate tissue-sparing surgical
      management. CONCLUSION: This case adds to our current knowledge about PDF and
      highlights the importance of early recognition of these lesions to direct
      appropriate diagnostic testing (full-thickness biopsy) and management. This case
      confirms successful management with Mohs surgery.

PMID- 28750559
TI  - Suppression of choroidal neovascularization in mice by subretinal delivery of
      multigenic lentiviral vectors encoding anti-angiogenic microRNAs.
AB  - Lentivirus-based vectors have been used for the development of potent gene
      therapies. Here, we present application of a multigenic lentiviral vector (LV)
      producing multiple anti-angiogenic microRNAs following subretinal delivery in a
      laser-induced choroidal neovascularization (CNV) mouse model. This versatile LV,
      carrying back-to-back RNApolII-driven expression cassettes, enables combined
      expression of microRNAs targeting vascular endothelial growth factor A (Vegfa)
      mRNA, and fluorescent reporters. In addition, by including a vitelliform macular
      dystrophy 2 (VMD2) promoter, expression of microRNAs is restricted to the retinal
      pigment epithelial (RPE) cells. Already 6 days post injection (PI) robust and
      widespread fluorescent signals of eGFP are observed in the retina by fundoscopy.
      The eGFP expression peaks at day 21 PI and persists with stable expression for at
      least 9 months. In parallel, prominent AsRED co-expression, encoded from the VMD2
      driven microRNA expression cassette, is evident in retinal sections and flat
      mounts, revealing RPE-specific expression of microRNAs. Furthermore, LV-delivered
      microRNAs targeting the Vegfa gene in RPE cells reduced the size of laser-induced
      CNV in mice 28 days PI, as a consequence of diminished VEGF levels, suggesting
      that LVs delivered locally are powerful tools in the development of gene therapy
      based strategies for treatment of age-related macular degeneration (AMD).

PMID- 28750560
TI  - Pharmacokinetic drug evaluation of lacosamide for the treatment of partial-onset
      seizures.
AB  - INTRODUCTION: The goal of pharmacologic therapy with antiepileptic drugs (AEDs)
      is to reduce the frequency of seizures and achieve a seizure-free state with
      minimal side effects. However 30% of patients treated with available AEDs
      continue to experience uncontrolled seizures. There is still need for new AEDs
      with enhanced effectiveness and tolerability. Areas covered: The present
      manuscript is based on an extensive Internet and PubMed search from 1992 to 2017.
      It is focused on the pharmacokinetic properties of lacosamide (LCM) for the
      treatment of partial-onset seizures. Expert opinion: LCM is an anticonvulsant
      approved as add-on treatment or monotherapy of partial-onset seizures with or
      without secondary generalization. LCM shares many of the pharmacokinetic
      characteristics of an ideal AED. LCM displays linear and dose-proportional
      pharmacokinetics, rapid and complete absorption from the gastrointestinal tract,
      low plasma-protein binding, renal excretion and a terminal half-life that
      supports twice-daily dosing. Because the bioavailability and tolerability of oral
      and intravenous LCM are comparable, LCM offers the advantage of direct conversion
      from oral to intravenous administration, and vice versa, without the need for
      titration or dose adjustment. Further studies are needed to determine optimal
      timing, dosing, as well as the safety and efficacy of LCM in status epilepticus.

PMID- 28750561
TI  - Renoprotective mechanisms of Astragaloside IV in cisplatin-induced acute kidney
      injury.
AB  - Nephrotoxicity remains a serious adverse effect of cisplatin chemotherapy,
      limiting its clinical usage. Numerous studies show that oxidative stress and
      inflammation are closely associated with cisplatin-induced renal damage.
      Astragaloside IV (AS-IV) has been found to possess antioxidant and anti
      inflammation functions. Therefore, we investigated the potential curative effects
      of AS-IV against cisplatin-induced renal injury and the possible cellular
      mechanism for activity, both in vitro and in vivo. We found that pretreatment of
      HK-2 cells with AS-IV could mitigate cisplatin-induced cell damage caused by
      oxygen-free radicals and the inflammatory response, as evidenced by reduced
      formation of reactive oxygen species (ROS) and inflammatory cytokines. AS-IV
      improved cisplatin-induced renal dysfunction and histopathological injury in
      mice. Additionally, AS-IV enhanced the activities of total superoxide dismutase
      (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). It also inhibited
      cisplatin-induced overproduction of kidney injury molecule-1 (KIM-1),
      malondialdehyde (MDA), tumour necrosis factor-alpha (TNF - alpha), and
      interleukin-1beta (IL-1beta) in kidney tissues. We found that the protective
      effects of AS-IV occurred via activation of the nuclear factor-erythroid 2
      related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins and inhibition of
      nuclear factor-kappaappaB (NF-kappaB) activation. Further, small interfering RNA
      (siRNA) knockdown of Nrf2 abrogated the protective effects of AS-IV against
      cisplatin-induced oxidative stress and blocked the inhibitory effects of AS-IV on
      cisplatin-induced NF-kappaB activation and inflammatory cytokine production. In
      conclusion, our data suggested that AS-IV attenuated cisplatin-mediated renal
      injury, and these protective effects might be due to inhibition of both oxidative
      damage and inflammatory response via activation of Nrf2 system and suppression of
      NF-kappaB activation.

PMID- 28750562
TI  - Successful endovascular treatment for thrombosed giant aneurysm of the V1 segment
      of the vertebral artery: A case report.
AB  - Thrombosed giant aneurysm of the V1 segment of the vertebral artery is rare, and
      there is controversy regarding the optimal method of treatment in this portion.
      Here, we report a thrombosed giant aneurysm of the V1 segment of the vertebral
      artery with a good clinical course with endovascular proximal artery occlusion of
      the vertebral artery. A 59-year-old woman presented with a large mass in the left
      side of the neck. Echographic examination revealed a mass measuring 42 * 38 * 48
      mm in the left neck. Angiography showed a thrombosed giant aneurysm of the V1
      segment of the left vertebral artery. Endovascular proximal artery occlusion of
      the vertebral artery was performed, and the aneurysm lessened gradually. Although
      a number of procedures have been developed to treat extracranial vertebral artery
      aneurysms, endovascular proximal artery occlusion is a good option to treat
      aneurysms in this portion.

PMID- 28750563
TI  - High-dose ascorbic acid induces carcinostatic effects through hydrogen peroxide
      and superoxide anion radical generation-induced cell death and growth arrest in
      human tongue carcinoma cells.
AB  - High-dose ascorbic acid (AsA) treatment, known as pharmacological AsA, has been
      shown to exert carcinostatic effects in many types of cancer cells and in vivo
      tumour models. Although pharmacological AsA has potential as a complementary and
      alternative medicine for anticancer treatment, its effects on human tongue
      carcinoma have not yet been elucidated. In this study, we investigated the effect
      of AsA treatment on human tongue carcinoma HSC-4 cells compared with non
      tumourigenic tongue epithelial dysplastic oral keratinocyte (DOK) cells. Our
      results show that treatment with 1 and 3 mM of AsA for 60 min preferentially
      inhibits the growth of human tongue carcinoma HSC-4 over DOK cells. Furthermore,
      AsA-induced effects were accompanied by increased intracellular oxidative stress
      and were repressed by treatment with a hydrogen peroxide (H2O2) scavenger
      catalase and a superoxide anion radical (O2-) scavenger, tempol. Time-lapse
      observation and thymidine analog EdU incorporation revealed that AsA treatment
      induces not only cell death but also suppression of DNA synthesis and cell
      growth. Moreover, the growth arrest was accompanied by abnormal cellular
      morphologies whereby cells extended dendrite-like pseudopodia. Taken together,
      our results demonstrate that AsA treatment can induce carcinostatic effects
      through induction of cell death, growth arrest, and morphological changes
      mediated by H2O2 and O2- generation. These findings suggest that high-dose AsA
      treatment represents an effective treatment for tongue cancer as well as for
      other types of cancer cells.

PMID- 28750564
TI  - Selective Antagonism of Bcl-xL Potentiates M1 Oncolysis by Enhancing
      Mitochondrial Apoptosis.
AB  - Oncolytic virotherapy is a novel and intriguing treatment strategy for cancer
      therapy. However, the clinical potential of oncolytic virus as single agent is
      limited. M1 virus is a promising oncolytic virus that has been tested in
      preclinical studies. In this study, we investigated the effect of the combination
      use of M1 virus and Bcl-2 family inhibitors. A chemical compounds screening
      including ten Bcl-2 family inhibitors demonstrated that pan-Bcl-2 inhibitors
      selectively augmented M1 virus oncolysis in cancer cells at very low doses. The
      mechanism of the enhanced antitumor effect of pan-Bcl-2 inhibitors with M1 virus
      is mainly due to the inhibition of Bcl-xL, which synergizes with M1-induced
      upregulation of Bak to trigger apoptosis. In xenograft mouse models and patient
      derived tumor tissues, the combination of M1 and pan-Bcl-2 inhibitors
      significantly inhibited tumor growth and prolonged survival, suggesting the
      potential therapeutic value of this strategy. These findings offer insights into
      the synergy between Bcl-xL inhibition and oncolytic virus M1 as a combination
      anticancer treatment modality.

PMID- 28750565
TI  - Digging deeper in relapsed acute lymphoblastic leukemia: impact of MRD status on
      outcome in second remission.

PMID- 28750566
TI  - Effect of cytogenetic risk status on outcomes for patients with acute myeloid
      leukemia undergoing various types of allogeneic hematopoietic cell
      transplantation: an analysis of 7812 patients.
AB  - This study aimed at determining how cytogenetic risk status affects outcomes for
      patients with acute myeloid leukemia (AML) after undergoing various types of
      allogeneic hematopoietic cell transplantation (HCT). Of 7812 patients eligible
      for analysis, cytogenetic risk was classified as favorable for 1088, intermediate
      for 5025, and poor for 1699. Overall, multivariate analysis showed significant
      intergroup differences in terms of relapse and survival, with the difference
      between poor- and intermediate-risk groups being greater than that between
      favorable- and intermediate-risk groups. Non-relapse mortality was identical for
      the three groups. Significant effects of cytogenetic risk status on survival were
      documented irrespective of donor type (related, unrelated, and umbilical cord
      blood), disease status at the time of transplantation (first or second complete
      remission, and more advanced disease status), and conditioning intensity
      (myeloablative and reduced-intensity). Our findings demonstrate robust and
      constant effects of cytogenetic risk status on survival after allogeneic HCT for
      patients with AML.

PMID- 28750567
TI  - Impact of pharmacogenomics upon the therapeutic response to etanercept in
      psoriasis and psoriatic arthritis.
AB  - INTRODUCTION: TNF-alpha inhibitors have demonstrated efficacy both as monotherapy
      and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the
      treatment of chronic inflammatory immune-mediated diseases. Etanercept is a decoy
      receptor" for TNF-alpha and it is composed of two p75 TNF-alpha receptors fused
      to human IgG1. Areas covered: We discuss the potential role of pharmacogenetics
      in predicting the response to etanercept in patients with Ps and PsA. Expert
      opinion: Pharmacogenetics represents the new frontier for the discovery of
      potential genetic markers of biological response to TNF-alpha inhibitors.
      Clinical studies showed that TNF-alpha -308 G/G, +489 GG and the +489 GA, TNF
      alpha -857C (rs1799724), TNFRSF1B 676T (rs1061622), TNFAIP3 G SNP (rs610604),
      FcgammaRIIIA-V158F, HLA-C*06, IL-17 A (rs2275913 and rs10484879), IL-17F
      (rs763780) and IL17RA (rs4819554) SNPs favor the response to etanercept. However,
      most of these studies are often small and not sufficiently powered to detect an
      effect and markers tend to be more prognostic than predictive of therapeutic
      response. Furthermore, studies often examines only the effects of a single SNP,
      while it would be more useful to analyze more haplotypes in contemporary in the
      same patients. Appropriately designed clinical trials are needed before a
      pharmacogenetic approach may be applicable in daily clinical therapeutic
      practice.

PMID- 28750568
TI  - Antipsychotic-induced Tardive dyskinesia: from biological basis to clinical
      management.
AB  - INTRODUCTION: Tardive dyskinesia (TD) is a chronic and disabling movement
      disorder with a complex pathophysiological basis. A significant percentage of
      patients does not receive correct diagnosis, resulting in delayed or inaccurate
      treatment and poor outcome. Therefore, there is a critical need for prompt
      recognition, implementation of efficacious treatment regimens and long-term
      follow up of patients with TD. Areas covered: The current paper provides an
      overview of emerging data concerning proposed pathophysiology theories,
      epidemiology, risk factors, and therapeutic strategies for TD. Expert commentary:
      Despite considerable research efforts, TD remains a challenge in the treatment of
      psychosis as the available strategies remain sub-optimal. The best scenario will
      always be the prophylaxis or prevention of TD, which entails limiting the use of
      antipsychotics.

PMID- 28750569
TI  - Improving the utility of the fine motor skills subscale of the comprehensive
      developmental inventory for infants and toddlers: a computerized adaptive test.
AB  - AIM: This study aimed at improving the utility of the fine motor subscale of the
      comprehensive developmental inventory for infants and toddlers (CDIIT) by
      developing a computerized adaptive test of fine motor skills. METHODS: We built
      an item bank for the computerized adaptive test of fine motor skills using the
      fine motor subscale of the CDIIT items fitting the Rasch model. We also examined
      the psychometric properties and efficiency of the computerized adaptive test of
      fine motor skills with simulated computerized adaptive tests. RESULTS AND
      CONCLUSIONS: Data from 1742 children with suspected developmental delays were
      retrieved. The mean scores of the fine motor subscale of the CDIIT increased
      along with age groups (mean scores = 1.36-36.97). The computerized adaptive test
      of fine motor skills contains 31 items meeting the Rasch model's assumptions
      (infit mean square = 0.57-1.21, outfit mean square = 0.11-1.17). For children of
      6-71 months, the computerized adaptive test of fine motor skills had high Rasch
      person reliability (average reliability >0.90), high concurrent validity (rs =
      0.67-0.99), adequate to excellent diagnostic accuracy (area under receiver
      operating characteristic = 0.71-1.00), and large responsiveness (effect size =
      1.05-3.93). The computerized adaptive test of fine motor skills used 48-84% fewer
      items than the fine motor subscale of the CDIIT. The computerized adaptive test
      of fine motor skills used fewer items for assessment but was as reliable and
      valid as the fine motor subscale of the CDIIT. Implications for Rehabilitation We
      developed a computerized adaptive test based on the comprehensive developmental
      inventory for infants and toddlers (CDIIT) for assessing fine motor skills. The
      computerized adaptive test has been shown to be efficient because it uses fewer
      items than the original measure and automatically presents the results right
      after the test is completed. The computerized adaptive test is as reliable and
      valid as the CDIIT.

PMID- 28750570
TI  - Identification of potential ibrutinib combinations in hematological malignancies
      using a combination high-throughput screen.
AB  - Matrix high-throughput screening (HTS) methods are increasingly employed to
      rapidly define potential therapeutic drug combinations. We used combination HTS
      to identify compounds showing synergistic anti-proliferative activity with
      ibrutinib, an irreversible, small-molecule inhibitor of Bruton's tyrosine kinase.
      The goal was to identify ibrutinib combinations with maximum synergistic effects
      in heme malignancy lines, particularly in non-Hodgkin lymphoma including diffuse
      large B-cell lymphoma (DLBCL). Growth inhibition (GI) was used to measure cell
      viability; synergy scores characterized strength of synergistic interaction.
      Single-agent ibrutinib demonstrated varying degrees of activity across 30 cell
      lines evaluated. In DLBCL lines, TMD8 was the most sensitive to ibrutinib (GI50 =
      0.001); combinations with BCL-2 inhibitor ABT-199, and PI3K inhibitors IPI-145
      and GDC-0941 showed the strongest synergistic activity. Anti-proliferative
      synergies were also observed with BET bromodomain inhibitor (+)-JQ1, XPO1
      inhibitor selinexor, and IRAK4 inhibitor, and confirmed using apoptosis assay.
      These findings are intended to inform and advance treatment of B-cell
      malignancies.

PMID- 28750571
TI  - A 50-bp Ins/Del polymorphism at the promoter region of the superoxide dismutase-1
      and bipolar disorder type 1.
AB  - Bipolar disorder type 1 (BPD) is a chronic psychiatric illness and is associated
      with oxidative stress. Superoxide dismutase-1 (SOD1; OMIM: 147450) metabolizes
      highly reactive and more dangerous superoxide radicals into less reactive
      molecules. A functional 50-bp insertion/deletion (Ins/Del) polymorphism in the
      promoter region of the gene has been reported. The primary aim of the current
      case-control study was to explore whether the SOD1 Ins/Del polymorphism
      associated with the risk of BPD. A secondary aim was to investigate the
      association between the study polymorphism and age of onset of BPD. The present
      case-control study was performed in Shiraz (southern Iran) on 228 BPD and 224
      healthy blood donor controls. The genotypes of the SOD1 Ins/Del polymorphism were
      determined by polymerase chain reaction. There was no significant association
      between the genotypes of Ins/Del polymorphism and the risk of BPD. Using Cox
      proportional hazards regression model, after adjustment for family history of
      BPD, revealed a significant association between the SOD1 Ins/Del polymorphism and
      age of onset. The age of onset was significantly lower for the Del/Del genotype
      than the 'Ins/Ins + Ins/Del' genotypes (hazard ratio = 2.33, 95%CI: 1.08-5.02, p
      = .030). Our present findings revealed that although the SOD1 Ins/Del
      polymorphism was not associated with the risk of BPD, it was significantly
      associated with age of onset of BPD.

PMID- 28750572
TI  - Small molecules as therapy for uveitis: a selected perspective of new and
      developing agents.
AB  - INTRODUCTION: Intraocular inflammation (uveitis) remains a significant burden of
      legal blindness. Because of its immune mediated and chronic recurrent nature,
      common therapy includes corticosteroids, disease-modifying anti-rheumatic drugs
      and more recently biologics as immune modulatory agents. The purpose of this
      article is to identify the role of new treatment approaches focusing on small
      molecules as therapeutic option in uveitis. Areas covered: A MEDLINE database
      search was conducted through February 2017 using the terms 'uveitis' and 'small
      molecule'. To provide ongoing and future perspectives in treatment options, also
      clinical trials as registered at ClinicalTrials.gov were included. Both, results
      from experimental as well as clinical research in this field were included. Since
      this field is rapidly evolving, a selection of promising agents had to be made.
      Expert opinion: Small molecules may interfere at different steps of the
      inflammatory cascade and appear as an interesting option in the treatment
      algorithm of uveitis. Because of their highly targeted molecular effects and
      their favorable bioavailability with the potential of topical application small
      molecules hold great promise. Nevertheless, a careful evaluation of these agents
      has to be made, since current experience is almost exclusively based on
      experimental uveitis models and few registered trials.

PMID- 28750574
TI  - Improving School Nurse Pain Assessment Practices for Students With Intellectual
      Disability.
AB  - School nurses are afforded minimal resources related to assessing pain in
      students with intellectual disability (ID) and have called for continuing
      education. The purpose of this study was to measure the effectiveness of an
      education program regarding best practices for assessing pain in students with
      ID. Educational sessions were presented to 248 school nurses. Pre-, post-, and
      follow-up surveys measured (1) difficulty school nurses face when assessing pain,
      (2) knowledge and use of pain assessment methods, and (3) intent to change and
      actual changes to professional practices. Participants experienced less
      difficulty assessing pain following the educational program. Almost all
      participants intended to change pain assessment practices, but large caseloads
      limited new practice adoption. Policy makers must consider population size and
      acuity when determining school nurse staffing. Trainings and other resources
      should be made available to school nurses in order to make pain assessments for
      students with ID more thorough and efficient.

PMID- 28750573
TI  - Life Is Precious: Views of Adolescents and Their Mothers on Methods to Reduce
      Suicidal Behavior in Latinas.
AB  - Life is Precious (LIP) was developed to help reduce suicidal behavior in Latina
      adolescents. As part of an external evaluation of the LIP program, we conducted
      focus groups with adolescent participants and mothers to learn whether
      participants and families believe that the activities of LIP address risks for
      suicidal behavior. Four focus groups were conducted: three with Latina adolescent
      LIP participants ( n = 31) and one with mothers ( n = 8). Transcripts were
      analyzed using ATLAS.ti. A grounded theory approach was used to identify themes
      and subthemes. The following themes emerged: (1) challenges contributing to
      suicidal behavior and self-harm among Latina adolescents, (2) how respondents
      believe that LIP is helping to reduce suicidal behavior, and 3) ongoing
      challenges. Participants say that the LIP program helps adolescents feel better
      and improve social relationships, academic performance, and relationships with
      their family. School nurses may wish to identify community-based programs
      offering similar services.

PMID- 28750575
TI  - Creation and Evaluation of New Porcine Model for Investigation of Treatments of
      Surgical Site Infection.
AB  - Surgical site infection (SSI) is the most common cause of surgical failure,
      increasing the risks of postoperative mortality and morbidity. Recently, it has
      been reported that the use of antimicrobial dressings at the incision site help
      with prevention of SSI. Despite the increased body of research on the development
      of different types of antimicrobial dressings for this application, to our
      knowledge, nobody has reported a reliable large animal model to evaluate the
      efficacy of developed materials in a preclinical SSI model. In this study, we
      developed a porcine full-thickness incision model to investigate SSI caused by
      methicillin-resistant Staphylococcus aureus (MRSA), the leading cause of SSI in
      the United States. Using this model, we then evaluated the efficacy of our newly
      developed silver releasing nanofibrous dressings for preventing and inhibiting
      MRSA infection. Our results confirmed the ease and practicality of a new porcine
      model as an in vivo platform for evaluation of biomaterials for SSI. Using this
      model, we found that our silver releasing scaffolds significantly reduced
      bacterial growth in wounds inoculated with MRSA relative to nontreated controls
      and to wounds treated with the gold standard, silver sulfadiazine, without
      causing inflammation at the wound site. Findings from this study confirm the
      potential of our silver-releasing nanofibrous scaffolds for treatment/prevention
      of SSI, and introduce a new porcine model for in vivo evaluation of additional
      SSI treatment approaches.

PMID- 28750576
TI  - Smartphone-based tele-electrocardiography support for primary care physicians
      reduces the pain-to-treatment time in acute coronary syndrome.
AB  - Background The Himachal Pradesh state acute coronary syndrome registry recorded a
      median delay of 13 h between the time of onset of pain to the time of making the
      diagnosis and giving treatment for acute coronary syndrome. We conducted a pilot
      study on providing 24-h tele-electrocardiography (Tele-ECG) services in the
      district Kangra of Himachal Pradesh, with the aim to reduce the time taken for
      diagnosis of acute coronary syndrome. Methods The intervention group for the
      study included eight rural community health centres, each with one to three
      primary care physicians, who were all unskilled in electrocardiogram
      interpretation. We provided them with 24-h Tele-ECG support. The primary care
      physicians used their smartphones to transmit the electrocardiogram image to the
      command centre, which was then read by the skilled specialist physicians in our
      medical college hospital and the report sent back within five minutes of having
      received the electrocardiogram. Antiplatelets were given by the primary care
      physician to patients diagnosed with acute coronary syndrome, who was then
      transported to the medical college hospital. The urban sub-divisional hospitals (
      n = 6) formed the control group for the study. These hospitals had five to
      fifteen unskilled primary care physicians and one to two skilled specialist
      physicians; no intervention was done in this group. A pilot was run from February
      2015-January 2016. Results We received 819 Tele-ECG consultations within the
      intervention group; 157 cases of acute coronary syndrome were confirmed and
      transferred to our medical college hospital facility. Similarly, we admitted 177
      cases of acute coronary syndrome at the medical college hospital, who were first
      attended to by the primary care physician in the control group. Aspirin was
      administered to 91% and 58% of patients with acute coronary syndrome in the
      intervention and the control groups, respectively ( p < 0.0001). The median
      hospital-to-aspirin time (h) in the intervention and the control groups was 0.7
      +/- 1.45 h and 3.5 +/- 10 h, respectively ( p < 0.0001). In the intervention
      group, 72% of the ST elevation myocardial infarction patients were diagnosed
      within 12 h by the primary care physician using Tele-ECG support. Interpretation
      and conclusions Smartphone-based Tele-ECG support for primary care physicians
      reduced the hospital-to-aspirin time in acute coronary syndrome significantly ( p
      < 0.0001). This is an effective low cost strategy and is easily replicable
      anywhere in the world.

PMID- 28750577
TI  - Assessing Option B+ retention and infant follow-up in Lilongwe, Malawi.
AB  - Malawi launched Option B+, a program for all pregnant or breastfeeding HIV
      positive women to begin lifelong combination antiretroviral therapy (cART), in
      July 2011. This study characterises a portion of the continuum of care within an
      antenatal setting in Lilongwe. Women testing HIV-positive and having a cART
      initiation record at Bwaila Antenatal Clinic from July 2013 to January 2014 were
      included. Using logistic regression models, we analysed relationships between
      maternal characteristics and return for infant testing. Among 490 HIV-positive
      women with a cART initiation record, 360 (73%) were retained at three months. Of
      these, 203 (56%) were adherent. Records of infant testing were located for 204
      women (42%). Women who were not retained were less likely to have an early infant
      diagnosis record (aOR = 0.20; 95% CI: 0.10, 0.41). Among the women retained,
      there was a non-significant association between maternal adherence and infant
      testing (OR = 1.35; 95% CI: 0.89, 2.06). Women lost at earlier continuum stages,
      who are at higher risk for mother-to-child-transmission, were less likely to
      bring infants for testing. Even with a test-and-treat program, many women did not
      remain in care or bring their infant for testing. Facilitating strategies to
      improve these measures remains an important unmet need.

PMID- 28750578
TI  - Dynamic predictions in Bayesian functional joint models for longitudinal and time
      to-event data: An application to Alzheimer's disease.
AB  - In the study of Alzheimer's disease, researchers often collect repeated
      measurements of clinical variables, event history, and functional data. If the
      health measurements deteriorate rapidly, patients may reach a level of cognitive
      impairment and are diagnosed as having dementia. An accurate prediction of the
      time to dementia based on the information collected is helpful for physicians to
      monitor patients' disease progression and to make early informed medical
      decisions. In this article, we first propose a functional joint model to account
      for functional predictors in both longitudinal and survival submodels in the
      joint modeling framework. We then develop a Bayesian approach for parameter
      estimation and a dynamic prediction framework for predicting the subjects' future
      outcome trajectories and risk of dementia, based on their scalar and functional
      measurements. The proposed Bayesian functional joint model provides a flexible
      framework to incorporate many features both in joint modeling of longitudinal and
      survival data and in functional data analysis. Our proposed model is evaluated by
      a simulation study and is applied to the motivating Alzheimer's Disease
      Neuroimaging Initiative study.

PMID- 28750579
TI  - Predictors of Back Pain in Firefighters.
AB  - The purpose of this study was to identify variables-that is, demographic factors
      (age, history of back pain, body mass index [BMI], and waist circumference),
      occupational stress, job satisfaction, perceived supervisor support, and physical
      fitness-that predict back pain in firefighters. Firefighters, an occupational
      group at high risk for back injury, perform many job tasks under hazardous work
      conditions. A nonexperimental, correlational design was used to study a
      convenience sample of 298 male firefighters who completed study questionnaires.
      Almost one third (30.20%) of the firefighters reported current back pain. The set
      of factors that predicted current back pain in firefighters included occupational
      stress, age, history of back pain, and BMI-pseudo R2 = .351. Further studies
      should validate the model and explore relationships among perceived supervisor
      support, occupational stress, and job satisfaction in other occupational groups,
      including nurses and police officers.

PMID- 28750580
TI  - Mortality and Self-Harm in Association With Clozapine in Treatment-Resistant
      Schizophrenia.
AB  - OBJECTIVE: This study evaluated rates of all-cause mortality and self-harm in
      association with clozapine treatment in individuals with treatment-resistant
      schizophrenia. METHOD: A population-based cohort of 2,370 individuals with
      treatment-resistant schizophrenia after Jan. 1, 1996, was followed until death,
      first episode of self-harm, emigration, or June 1, 2013. Time to all-cause death
      and time to first episode of self-harm were analyzed in Cox regression models
      with time-varying treatment, adjusted for clinical and sociodemographic
      covariates. RESULTS: The rate of all-cause mortality was higher for patients not
      receiving clozapine than for those given clozapine (hazard ratio: 1.88, 95%
      confidence interval [CI]: 1.16-3.05). This was driven mainly by periods of no
      antipsychotic treatment (hazard ratio: 2.50, 95% CI: 1.50-4.17), with
      nonsignificantly higher mortality during treatment with other antipsychotics
      (hazard ratio: 1.45, 95% CI: 0.86-2.45). Excess mortality was observed in the
      year after clozapine discontinuation (hazard ratio: 2.65, 95% CI: 1.47-4.78). The
      rate of self-harm was higher for nonclozapine antipsychotics than for clozapine
      (hazard ratio: 1.36, 95% CI: 1.04-1.78). CONCLUSIONS: The results demonstrate a
      nearly twofold higher mortality rate among individuals with treatment-resistant
      schizophrenia not treated with clozapine compared with clozapine-treated
      individuals. Furthermore, the results suggest a harmful effect of other
      antipsychotics regarding self-harm compared with clozapine. It remains to be
      investigated to what extent the observed excess mortality after clozapine
      discontinuation is confounded by nonadherence and other unobserved factors and to
      what extent it is mediated by adverse effects from recent clozapine exposure or
      deterioration in physical or mental health precipitated by clozapine
      discontinuation.

PMID- 28750582
TI  - Efficacy and Safety of MIN-101: A 12-Week Randomized, Double-Blind, Placebo
      Controlled Trial of a New Drug in Development for the Treatment of Negative
      Symptoms in Schizophrenia.
AB  - OBJECTIVE: The authors assessed the efficacy, safety, and tolerability of MIN
      101, a compound with affinities for sigma-2 and 5-HT2A receptors and no direct
      dopamine affinities, in comparison with placebo in treating negative symptoms in
      stabilized patients with schizophrenia. METHOD: The trial enrolled 244 patients
      who had been symptomatically stable for at least 3 months and had scores of at
      least 20 on the negative subscale of the Positive and Negative Syndrome Scale
      (PANSS). After at least 5 days' withdrawal from all antipsychotic medication,
      patients were randomly assigned to receive placebo or 32 mg/day or 64 mg/day of
      MIN-101 for 12 weeks. The primary outcome measure was the PANSS negative factor
      score (pentagonal structure model). Secondary outcome measures were PANSS total
      score and scores on the Clinical Global Impressions Scale (CGI), the Brief
      Negative Symptom Scale, the Brief Assessment of Cognition in Schizophrenia, and
      the Calgary Depression Scale for Schizophrenia. RESULTS: A statistically
      significant difference in PANSS negative factor score was observed, with lower
      scores for the MIN-101 32 mg/day and 64 mg/day groups compared with the placebo
      group (effect sizes, d=0.45 and d=0.57, respectively). Supporting these findings
      were similar effects on several of the secondary outcome measures, such as the
      PANSS negative symptom, total, and activation factor scores, the CGI severity
      item, and the Brief Negative Symptom Scale. There were no statistically
      significant differences in PANSS positive scale score between the MIN-101 and
      placebo groups. No clinically significant changes were observed in vital signs,
      routine laboratory values, weight, metabolic indices, and Abnormal Involuntary
      Movement Scale score. CONCLUSIONS: MIN-101 demonstrated statistically significant
      efficacy in reducing negative symptoms and good tolerability in stable
      schizophrenia patients.

PMID- 28750581
TI  - Rare Genome-Wide Copy Number Variation and Expression of Schizophrenia in 22q11.2
      Deletion Syndrome.
AB  - OBJECTIVE: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a
      more than 20-fold increased risk for developing schizophrenia. The aim of this
      study was to identify additional genetic factors (i.e., "second hits") that may
      contribute to schizophrenia expression. METHOD: Through an international
      consortium, the authors obtained DNA samples from 329 psychiatrically phenotyped
      subjects with 22q11.2DS. Using a high-resolution microarray platform and
      established methods to assess copy number variation (CNV), the authors compared
      the genome-wide burden of rare autosomal CNV, outside of the 22q11.2 deletion
      region, between two groups: a schizophrenia group and those with no psychotic
      disorder at age >=25 years. The authors assessed whether genes overlapped by rare
      CNVs were overrepresented in functional pathways relevant to schizophrenia.
      RESULTS: Rare CNVs overlapping one or more protein-coding genes revealed
      significant between-group differences. For rare exonic duplications, six of 19
      gene sets tested were enriched in the schizophrenia group; genes associated with
      abnormal nervous system phenotypes remained significant in a stepwise logistic
      regression model and showed significant interactions with 22q11.2 deletion region
      genes in a connectivity analysis. For rare exonic deletions, the schizophrenia
      group had, on average, more genes overlapped. The additional rare CNVs implicated
      known (e.g., GRM7, 15q13.3, 16p12.2) and novel schizophrenia risk genes and loci.
      CONCLUSIONS: The results suggest that additional rare CNVs overlapping genes
      outside of the 22q11.2 deletion region contribute to schizophrenia risk in
      22q11.2DS, supporting a multigenic hypothesis for schizophrenia. The findings
      have implications for understanding expression of psychotic illness and herald
      the importance of whole-genome sequencing to appreciate the overall genomic
      architecture of schizophrenia.

PMID- 28750584
TI  - Correlations Between Personality, Affective and Filial Self-Efficacy Beliefs, and
      Psychological Well-Being in a Sample of Italian Adolescents.
AB  - Adolescence is a critical period for the emergence of a balanced personality in
      adults. Extraversion, neuroticism, and affective self-efficacy beliefs in emotion
      regulation showed to be good predictors of psychological well-being in
      adolescents. We analyzed the association between affective self-efficacy beliefs,
      personality traits, and psychological well-being of 179 Italian adolescents. We
      also analyzed the connection between adolescents' filial self-efficacy beliefs
      and psychological well-being and possible moderating effects of self-efficacy
      beliefs on personality traits. Results show that extraversion, neuroticism, and
      self-efficacy beliefs in emotion regulation are correlated with psychological
      well-being, while filial self-efficacy does not. Self-efficacy beliefs do not
      show significant moderating effects on personality traits, even if self-efficacy
      beliefs in expressing positive emotions reduce negative characteristics of
      individuals with high level of psychoticism.

PMID- 28750583
TI  - Association of a History of Child Abuse With Impaired Myelination in the Anterior
      Cingulate Cortex: Convergent Epigenetic, Transcriptional, and Morphological
      Evidence.
AB  - OBJECTIVE: Child abuse has devastating and long-lasting consequences,
      considerably increasing the lifetime risk of negative mental health outcomes such
      as depression and suicide. Yet the neurobiological processes underlying this
      heightened vulnerability remain poorly understood. The authors investigated the
      hypothesis that epigenetic, transcriptomic, and cellular adaptations may occur in
      the anterior cingulate cortex as a function of child abuse. METHOD: Postmortem
      brain samples from human subjects (N=78) and from a rodent model of the impact of
      early-life environment (N=24) were analyzed. The human samples were from
      depressed individuals who died by suicide, with (N=27) or without (N=25) a
      history of severe child abuse, as well as from psychiatrically healthy control
      subjects (N=26). Genome-wide DNA methylation and gene expression were
      investigated using reduced representation bisulfite sequencing and RNA
      sequencing, respectively. Cell type-specific validation of differentially
      methylated loci was performed after fluorescence-activated cell sorting of
      oligodendrocyte and neuronal nuclei. Differential gene expression was validated
      using NanoString technology. Finally, oligodendrocytes and myelinated axons were
      analyzed using stereology and coherent anti-Stokes Raman scattering microscopy.
      RESULTS: A history of child abuse was associated with cell type-specific changes
      in DNA methylation of oligodendrocyte genes and a global impairment of the myelin
      related transcriptional program. These effects were absent in the depressed
      suicide completers with no history of child abuse, and they were strongly
      correlated with myelin gene expression changes observed in the animal model.
      Furthermore, a selective and significant reduction in the thickness of myelin
      sheaths around small-diameter axons was observed in individuals with history of
      child abuse. CONCLUSIONS: The results suggest that child abuse, in part through
      epigenetic reprogramming of oligodendrocytes, may lastingly disrupt cortical
      myelination, a fundamental feature of cerebral connectivity.

PMID- 28750585
TI  - Nutritional ketone salts increase fat oxidation but impair high-intensity
      exercise performance in healthy adult males.
AB  - This study investigated the impact of raising plasma beta-hydroxybutyrate (beta
      OHB) through ingestion of ketone salts on substrate oxidation and performance
      during cycling exercise. Ten healthy adult males (age, 23 +/- 3 years; body mass
      index, 25 +/- 3 kg/m2, peak oxygen uptake, 45 +/- 10 mL/(kg.min)-1) were
      recruited to complete 2 experimental trials. Before enrollment in the
      experimental conditions, baseline anthropometrics and cardiorespiratory fitness
      (peak oxygen uptake) were assessed and familiarization to the study protocol was
      provided. On experimental days, participants reported to the laboratory in the
      fasted state and consumed either 0.3 g/kg beta-OHB ketone salts or a flavour
      matched placebo at 30 min prior to engaging in cycling exercise. Subjects
      completed steady-state exercise at 30%, 60%, and 90% ventilatory threshold (VT)
      followed by a 150-kJ cycling time-trial. Respiratory exchange ratio (RER) and
      total substrate oxidation were derived from indirect calorimetry. Plasma glucose,
      lactate, and ketones were measured at baseline, 30 min post-supplement, post
      steady-state exercise, and immediately following the time-trial. Plasma beta-OHB
      was elevated from baseline and throughout the entire protocol in the ketone
      condition (p < 0.05). RER was lower at 30% and 60% VT in the ketone compared with
      control condition. Total fat oxidation was greater in the ketone versus control
      (p = 0.05). Average time-trial power output was ~7% lower (-16 W, p = 0.029) in
      the ketone condition. Ingestion of ketone salts prior to exercise increases fat
      oxidation during steady-state exercise but impairs high-intensity exercise
      performance.

PMID- 28750586
TI  - A controlled clinical trial of a clinically-tuned powered ankle prosthesis in
      people with transtibial amputation.
AB  - OBJECTIVE: To determine whether there are changes in level walking performance
      for people using a powered ankle prosthesis that was tuned by an independent,
      manufacturer-certified prosthetist in accordance with device recommendations.
      DESIGN: Intervention study with cross-over design. SETTING: Laboratory.
      PARTICIPANTS: Convenience sample of 10 individuals with unilateral, transtibial
      amputation, and 10 age- and gender-matched control participants. INTERVENTIONS:
      Powered ankle prosthesis (BiOM T2 Ankle System). Main outcome metrics: Metabolic
      costs of walking, preferred walking speed. RESULTS: There were no significant
      differences in oxygen consumption (2.9% difference; P = 0.606, d = 0.26), cost of
      transport (~1% difference; P = 0.652, d = 0.23), or preferred walking speed (~1%
      difference; P = 0.147, d = 0.76) when using the powered ankle compared to
      unpowered prostheses. Secondary analyses of user characteristics revealed that
      participants who were classified as having the highest function (K4 on Medicare's
      5-point scale from K0 to K4) were significantly more likely to exhibit energy
      cost savings than those classified as having lower function (K3; P = 0.014, d =
      2.36). CONCLUSIONS: Participants did not demonstrate significant improvements in
      energetics or preferred speed when wearing a clinically tuned powered ankle
      prosthesis compared to their non-powered prostheses. Prescribers of powered
      devices should understand that not all users will show an immediate reduction in
      energy expenditure.

PMID- 28750587
TI  - Lack of habituation of visual evoked potentials in migraine and healthy subjects:
      Correlated cognitive behavioral aspects.

PMID- 28750588
TI  - Efficacy of strength training on tension-type headache: A randomised controlled
      study.
AB  - Background Strength training has shown effects in reducing neck pain. As neck
      pain is highly prevalent in tension-type headache (TTH), it is relevant to
      examine the effect of strength training of the shoulder muscles on TTH patients.
      Aim To examine the effect of strength training of the shoulder/neck muscles on
      TTH frequency and duration. Methods Sixty patients with TTH were randomised into
      strength training or a control group. The strength training group trained ten
      weeks with elastic resistance bands. The control group performed ergonomic and
      posture correction. Efficacy was evaluated at follow-up after 19-22 weeks.
      Results Twenty-three patients completed strength training and 21 completed
      ergonomic and posture correction (per-protocol). No between-group effect was
      detected, but within groups numerical reductions were noted in both groups from
      baseline to follow-up. Frequency of TTH in the strength training group decreased
      by 11% ( P = 0.041) and duration decreased by10% ( P = 0.036), while the
      ergonomic and posture correction group showed a significant reduction in
      frequency of 24% ( P = 0.0033) and a decrease in duration of 27% ( P = 0.041).
      Conclusion No significant difference between the groups was found and the within
      group effects did not reach clinical significance. Combining all the elements
      into a multifaceted intervention could prove more useful and should be further
      explored in future studies. Clinical trials registration number NCT02984826.

PMID- 28750589
TI  - Brain atrophy following hemiplegic migraine attacks.
AB  - Background Patients with hemiplegic migraine (HM) may sometimes develop
      progressive neurological deterioration of which the pathophysiology is unknown.
      Patient We report a 16-year clinical and neuroradiological follow-up of a patient
      carrying a de novo p.Ser218Leu CACNA1A HM mutation who had nine severe HM attacks
      associated with seizures and decreased consciousness between the ages of 3 and 12
      years. Results Repeated ictal and postictal neuroimaging revealed cytotoxic
      oedema during severe HM attacks in the symptomatic hemisphere, which later showed
      atrophic changes. In addition, progressive cerebellar atrophy was observed. Brain
      atrophy halted after cessation of severe attacks, possibly due to prophylactic
      treatment with flunarizine and sodium valproate. Conclusion Severe HM attacks may
      result in brain atrophy and prophylactic treatment of these attacks might be
      needed in an early stage of disease to prevent permanent brain damage.

PMID- 28750590
TI  - Initiation of spreading depression by synaptic and network hyperactivity:
      Insights into trigger mechanisms of migraine aura.
AB  - Background Cortical spreading depression (SD) is thought to underlie migraine
      aura but mechanisms of triggering SD in the structurally normal, well-nourished
      cortex of migraine patients remain unknown. Synaptic and network dysfunctions
      appear to underlie episodic neurological disorders, including migraine. The
      narrative review summarizes old and recent experimental evidence for triggering
      SD by synaptic/network mechanisms and discusses the relevance of the data to
      migraine pathogenesis. Our hypothesis is that under some conditions
      synaptic/network hyperactivity may reliably ignite SD, and this mechanism may
      underlie triggering migraine aura in patients. Findings High-frequency tetanic
      stimulation of the cortex reliably triggers SD in synaptically connected regions;
      SD is a reliable cortical response to acute hyperexcitability (epileptic
      seizures), though chronic epilepsy prevents triggering SD; in the hyperexcitable
      cortex, SD may be triggered by sensory stimulation; compromised glutamatergic
      transmission plays the critical role in triggering SD. Conclusion SD may be
      triggered by dynamic network instability produced by dysfunction of calcium
      dependent glutamate release. Synaptic drive from subcortical sensory processing
      structures (brainstem and/or thalamocortical networks) is able to evoke
      depolarization of hyperexcitable cortical neurons sufficient to initiate the
      regenerative SD process. Studying SD initiation by synaptic/network
      hyperexcitability may provide insights into basic mechanisms underlying SD
      generation in migraine brain.

PMID- 28750591
TI  - Five-dimensional long bones biometry for estimation of femur length and fetal
      weight at term compared to two-dimensional ultrasound: a pilot study.
AB  - BACKGROUND/OBJECTIVE: This study aimed to evaluate accuracy of five-dimensional
      long bones (5D LB) compared to two-dimensional ultrasound (2DUS) biometry to
      predict fetal weight among normal term women. METHODS: Fifty six normal term
      women were recruited at Ain Shams Maternity Hospital, Egypt from 14 May to 30
      November 2015. Fetal weight was estimated by Hadlock's IV formula using 2DUS and
      5D LB. Estimated fetal weights (EFW) by 2DUS and 5D LB were compared with actual
      birth weights (ABW). RESULTS: Mean femur length (FL) was 7.07 +/- 0.73 cm and
      6.74 +/- 0.67 cm by 2DUS and 5D LB (p = .02). EFW was 3309.86 +/- 463.06 g by
      2DUS and 3205.46 +/- 447.85 g by 5D LB (p = .25). No statistical difference was
      observed between ABW and EFW by 2DUS (p = .7) or 5D LB (p = .45). Positive
      correlation was found between EFW by 2DUS, 5D LB, and ABW (r = 0.67 and 0.7; p <
      .001). There was strong agreement between FL measured by 2DUS and 5D LB (ICC =
      0.78), and perfect agreement between EFW by 2DUS and EFW by 5D LB (ICC = 0.918).
      2DUS and 5D LB showed mean absolute percentage error for EFW of 10 +/- 7% and 8
      +/- 7% compared to ABW (p = .15). CONCLUSIONS: 2DUS and 5D LB had same accuracy
      for fetal weight estimation at normal term pregnancy.

PMID- 28750592
TI  - FDG PET-CT evaluation in neurolymphomatosis: imaging characteristics and clinical
      outcomes.
AB  - Neurolymphomatosis (NL) often represents unidentified non-Hodgkin lymphoma
      relapses. Considering its severity, early detection and treatment are crucial. We
      outline one hospital's 18F-FDG-PET-CT imaging findings of NL, along with the
      patients' clinical characteristics. Clinical records and imaging findings of 19
      NL patients, PET-CT diagnosed, were retrospectively reviewed. Patient data, FDG
      PET-CT findings and the presence of coexisting diseases, especially CNS
      involvement, were documented. Available MRI and clinical data verified the
      findings. All cases had increased linear FDG uptake along anatomic nerve sites.
      CTs showed varying degrees of corresponding soft-tissue-thickening. Clinical
      correlations also contributed to the diagnosis. In 4/19 patients, lymphoma
      presented with NL, in 15/19 it appeared with disease recurrence/progression. In
      9/19, clinical symptoms suggested neural involvement while 10/19 had nonspecific
      symptoms. Eleven died of lymphoma within 0.9 years of diagnosis despite directed
      therapy. Eight, however, survived up to 7.82 years post-diagnosis. Whole-body FDG
      PET-CT can assist in early NL diagnosis, possibly enhancing survival.

PMID- 28750593
TI  - The role of external beam radiation therapy in well-differentiated thyroid
      cancer.
AB  - INTRODUCTION: This review article explores the use of external beam radiotherapy
      (EBRT) in well differentiated thyroid cancer. Areas covered: The published
      literature on EBRT for advanced pT4 disease and macroscopic unresectable disease
      to improve locoregional control is reviewed. EBRT techniques, volumes and doses
      are discussed in detail. The potential acute and late toxicities of EBRT are
      discussed in the context of the published literature. The use of EBRT for
      patients with metastatic disease is also described. Expert commentary: There is
      good retrospective evidence for EBRT in the setting of unresectable gross
      residual well-differentiated thyroid cancer as this can result in long-term local
      control. However, the benefit of EBRT in patients with locally advanced disease
      that is completely resected is less clear. The use of EBRT for these patients
      requires careful consideration of age, pathologic factors, comorbidities and
      patient preference, preferably by a multi-disciplinary team.

PMID- 28750594
TI  - Global capacity, potentials and trends of solid waste research and management.
AB  - In this study, United States, China, India, United Kingdom, Nigeria, Egypt,
      Brazil, Italy, Germany, Taiwan, Australia, Canada and Mexico were selected to
      represent the global community. This enabled an overview of solid waste
      management worldwide and between developed and developing countries. These are
      countries that feature most in the International Conference on Solid Waste
      Technology and Management (ICSW) over the past 20 years. A total of 1452 articles
      directly on solid waste management and technology were reviewed and credited to
      their original country of research. Results show significant solid waste research
      potentials globally, with the United States leading by 373 articles, followed by
      India with 230 articles. The rest of the countries are ranked in the order of: UK
      > Taiwan > Brazil > Nigeria > Italy > Japan > China > Canada > Germany >Mexico >
      Egypt > Australia. Global capacity in solid waste management options is in the
      order of: Waste characterisation-management > waste biotech/composting > waste to
      landfill > waste recovery/reduction > waste in construction > waste recycling >
      waste treatment-reuse-storage > waste to energy > waste dumping > waste
      education/public participation/policy. It is observed that the solid waste
      research potential is not a measure of solid waste management capacity. The
      results show more significant research impacts on solid waste management in
      developed countries than in developing countries where economy, technology and
      society factors are not strong. This article is targeted to motivate similar
      study in each country, using solid waste research articles from other streamed
      databases to measure research impacts on solid waste management.

PMID- 28750595
TI  - Selective Attention in Pigeon Temporal Discrimination.
AB  - Cues can vary in how informative they are about when specific outcomes, such as
      food availability, will occur. This study was an experimental investigation of
      the functional relation between cue informativeness and temporal discrimination
      in a peak-interval (PI) procedure. Each session consisted of fixed-interval (FI)
      2-s and 4-s schedules of food and occasional, 12-s PI trials during which pecks
      had no programmed consequences. Across conditions, the phi (phi) correlation
      between key light color and FI schedule value was manipulated. Red and green key
      lights signaled the onset of either or both FI schedules. Different colors were
      either predictive (phi = 1), moderately predictive (phi = 0.2-0.8), or not
      predictive (phi = 0) of a specific FI schedule. This study tested the hypothesis
      that temporal discrimination is a function of the momentary conditional
      probability of food; that is, pigeons peck the most at either 2 s or 4 s when phi
      = 1 and peck at both intervals when phi < 1. Response distributions were bimodal
      Gaussian curves; distributions from red- and green-key PI trials converged when
      phi <= 0.6. Peak times estimated by summed Gaussian functions, averaged across
      conditions and pigeons, were 1.85 s and 3.87 s, however, pigeons did not always
      maximize the momentary probability of food. When key light color was highly
      correlated with FI schedules (phi >= 0.6), estimates of peak times indicated that
      temporal discrimination accuracy was reduced at the unlikely interval, but not
      the likely interval. The mechanism of this reduced temporal discrimination
      accuracy could be interpreted as an attentional process.

PMID- 28750596
TI  - (RT)-qPCR for detection of and differentiation between RNA and DNA of HIV-1-based
      lentiviral vectors.
AB  - The purpose of the described method is the detection of and differentiation
      between RNA and DNA of HIV-derived lentiviral vectors (LV) in cell culture
      supernatants and swab samples. For the analytical surveillance of genetic
      engineering operations methods for the detection of the HIV-1 based LV
      generations are required. Furthermore, for research issues, it is important to
      prove the absence of LV particles for downgrading experimental settings in terms
      of the biosafety level. Here a qPCR method targeting the LTR U5 subunit and the
      start sequence of the packaging signal psi is described. Numerous controls are
      included in order to monitor the technical procedure.

PMID- 28750597
TI  - A maternal high-fat/high-caloric diet delays reflex ontogeny during lactation but
      enhances locomotor performance during late adolescence in rats.
AB  - OBJECTIVE: The main goal of the present study was to investigate the effects of
      two maternal high-fat diets with different energy densities on the somatic
      growth, reflex ontogeny, and locomotor activity of offspring. METHODS: Twenty
      nine female Wistar rats (220-250 g) were mated and grouped into three different
      dietary conditions: control (n = 11, AIN-93G diet, 3.6 kcal/g), high-fat/high
      caloric (HH, n = 9, 51% of the calories from fat, 4.62 kcal/g), and high
      fat/isocaloric (HI, n = 9, 51% of the calories from fat, 3.64 kcal/g). The fat
      source was mainly lard. The dietary groups were maintained during gestation and
      lactation. From postnatal day 1 (PND1) until weaning, the somatic growth,
      maturation of physical features, and reflex ontogeny of the male pups were
      evaluated. The locomotor activity was evaluated in an open field at PND8, PND14,
      PND17, PND21, PND30, PND45, and PND60. RESULTS: HH dams had a lower food intake
      but no difference in caloric intake or body weight gain. The HH pups had higher
      body weights, greater tail and body lengths, and an increased axis of the head at
      weaning. The prediction of ear unfolding, delayed palmar grasp, and cliff
      avoidance maturation were also observed in the HH offspring. At PND60, the HH
      pups showed an increased average speed as well as an average potency and kinetic
      energy in the open field. CONCLUSION: A high-fat/high-caloric maternal diet
      increases somatic growth, predicts the maturation of physical features, and
      delays reflex ontogeny during lactation, and it enhances motor performance during
      late adolescence. A maternal HI diet does not elicit the same influences on
      offspring development compared with the HH diet.

PMID- 28750598
TI  - Hemodynamic Instability Secondary to Vasopressin Withdrawal in Septic Shock.
AB  - RATIONALE: Vasopressors such as norepinephrine are first line for support of mean
      arterial pressure (MAP) in the management of septic shock. Their use, however, is
      commonly associated with many adverse events. These detriments frequently trigger
      the use of alternative, noncatecholamine therapies, including vasopressin.
      Vasopressin deficiency is a known physiologic consequence of septic shock, and
      while guidelines recommend vasopressin in addition to norepinephrine, no
      consensus exists on the duration of deficiency or ideal time of cessation.
      Studies have suggested that vasopressin discontinuation prior to other
      vasopressors may lead to hypotension; however, data are limited. This study
      evaluates the optimal sequence for the discontinuation of vasopressin therapy in
      septic shock. METHODS: This was a 1-year retrospective study of 152 patients
      admitted to the medical intensive care unit (ICU) with septic shock who received
      concurrent norepinephrine and vasopressin for vasoactive support. Patients were
      excluded if death occurred on vasopressors, within 24 hours after discontinuation
      of vasopressors, or within 48 hours of ICU admission. The primary outcome of
      hemodynamic instability included incidence of hypotension after vasopressor
      discontinuation (2 consecutive MAPs < 60 mm Hg), fluid bolus administration,
      greater than 0.05 MUg/kg/min increase in norepinephrine requirements, or addition
      of an alternative vasopressor. Secondary outcomes included time to hypotension,
      total vasopressor duration, arrhythmias, mortality, and length of stay. RESULTS:
      Ninety-one patients met exclusion criteria, resulting in 61 patients for
      evaluation. Vasopressin was the first vasoactive therapy to be discontinued in 19
      patients and last in 42 patients. Baseline characteristics and the use of
      potentially confounding treatments known to effect MAP were similar between
      groups. Discontinuation of vasopressin first was associated with a significant
      increase in hemodynamic instability (74% vs 16.7%, P < .01), with a shorter time
      to hemodynamic instability (5 vs 15 hours, P < .01). Secondary outcomes were
      similar. CONCLUSION: Vasopressin discontinuation prior to cessation of
      norepinephrine infusion was associated with an increased risk of hemodynamic
      instability.

PMID- 28750599
TI  - The influence of multiple trials and computer-mediated communication on
      collaborative and individual semantic recall.
AB  - Collaborative inhibition is a phenomenon where collaborating groups experience a
      decrement in recall when interacting with others. Despite this, collaboration has
      been found to improve subsequent individual recall. We explore these effects in
      semantic recall, which is seldom studied in collaborative retrieval. We also
      examine "parallel CMC", a synchronous form of computer-mediated communication
      that has previously been found to improve collaborative recall [Hinds, J. M., &
      Payne, S. J. (2016). Collaborative inhibition and semantic recall: Improving
      collaboration through computer-mediated communication. Applied Cognitive
      Psychology, 30(4), 554-565]. Sixty three triads completed a semantic recall task,
      which involved generating words beginning with "PO" or "HE" across three recall
      trials, in one of three retrieval conditions: Individual-Individual-Individual
      (III), Face-to-face-Face-to-Face-Individual (FFI) and Parallel-Parallel
      Individual (PPI). Collaborative inhibition was present across both collaborative
      conditions. Individual recall in Recall 3 was higher when participants had
      previously collaborated in comparison to recalling three times individually.
      There was no difference between face-to-face and parallel CMC recall, however
      subsidiary analyses of instance repetitions and subjective organisation
      highlighted differences in group members' approaches to recall in terms of
      organisation and attention to others' contributions. We discuss the implications
      of these findings in relation to retrieval strategy disruption.

PMID- 28750600
TI  - Towards modular bone tissue engineering using Ti-Co-doped phosphate glass
      microspheres: cytocompatibility and dynamic culture studies.
AB  - The production of large quantities of functional vascularized bone tissue ex vivo
      still represent an unmet clinical challenge. Microcarriers offer a potential
      solution to scalable manufacture of bone tissue due to their high surface area-to
      volume ratio and the capacity to be assembled using a modular approach.
      Microcarriers made of phosphate bioactive glass doped with titanium dioxide have
      been previously shown to enhance proliferation of osteoblast progenitors and
      maturation towards functional osteoblasts. Furthemore, doping with cobalt appears
      to mimic hypoxic conditions that have a key role in promoting angiogenesis. This
      characteristic could be exploited to meet the clinical requirement of producing
      vascularized units of bone tissue. In the current study, the human osteosarcoma
      cell line MG-63 was cultured on phosphate glass microspheres doped with 5% mol
      titanium dioxide and different concentrations of cobalt oxide (0%, 2% and 5%
      mol), under static and dynamic conditions (150 and 300 rpm on an orbital shaker).
      Cell proliferation and the formation of aggregates of cells and microspheres were
      observed over a period of two weeks in all glass compositions, thus confirming
      the biocompatibility of the substrate and the suitability of this system for the
      formation of compact micro-units of tissue. At the concentrations tested, cobalt
      was not found to be cytotoxic and did not alter cell metabolism. On the other
      hand, the dynamic environment played a key role, with moderate agitation having a
      positive effect on cell proliferation while higher agitation resulting in
      impaired cell growth. Finally, in static culture assays, the capacity of cobalt
      doping to induce vascular endothelial growth factor (VEGF) upregulation by
      osteoblastic cells was observed, but was not found to increase linearly with
      cobalt oxide content. In conclusion, Ti-Co phosphate glasses were found to
      support osteoblastic cell growth and aggregate formation that is a necessary
      precursor to tissue formation and the upregaulation of VEGF production can
      potentially support vascularization.

PMID- 28750601
TI  - Development and characterization of antibacterial braided polyamide suture coated
      with chitosan-citric acid biopolymer.
AB  - Braided polyamide sutures are frequently used in dermatologic surgery for wound
      closure. However, braided sutures promote bacteria proliferation. In order to
      prevent wound complications due to this effect, antibacterial sutures should be
      used. The main objective of this study is the development of new non-absorbable
      antibacterial polyamide braided suture. This paper suggests new coating process
      that leads to obtain suture uniformly covered by antibacterial film enclosing
      chitosan, which is known for its antibacterial benefit. Mechanical properties and
      surface morphology of developed sutures were investigated by using mechanical
      tests. Sutures surfaces were also examined by scanning electron microscope, to
      perceive spreading of coating product on suture surface. In order to identify
      potential reactions between chemical compounds present in coating solution and
      suture material, sutures were analyzed by ATR-IF spectroscopy. It has been
      demonstrated that many eventual bonds between compounds present in coating
      solutions and polyamide macromolecular chain may occur. The existence of these
      bonds implies the fixation of biopolymer coating on suture surface. It has been
      demonstrated that uniform surface may be obtained by progressively applying
      coating solution containing little amount of chitosan on suture surface. We have
      also found that developed coating process has not affected mechanical properties
      of suture, which still meet United States Pharmacopeia requirement. Finally,
      antibacterial effects against four colonies, very widespread in hospitals, were
      studied. Prominent antibacterial effects of braided polyamide suture against two
      gram-positive ( S Aureus, S epidermidis) and two gram-negative ( E coli and P
      aeruginosa) colonies are presented. Optimal result of best properties is obtained
      by applying three layers of biopolymer coating comprising 1% chitosan and 10%
      citric acid. The new developed suture coating process appears as a promising
      method for obtaining important antibacterial effect with smooth suture surface.

PMID- 28750602
TI  - Mechanical induction of bi-directional orientation of primary porcine bladder
      smooth muscle cells in tubular fibrin-poly(vinylidene fluoride) scaffolds for
      ureteral and urethral repair using cyclic and focal balloon catheter stimulation.
AB  - To restore damaged organ function or to investigate organ mechanisms, it is
      necessary to prepare replicates that follow the biological role model as
      faithfully as possible. The interdisciplinary field of tissue engineering has
      great potential in regenerative medicine and might overcome negative side effects
      in the replacement of damaged organs. In particular, tubular organ structures of
      the genitourinary tract, such as the ureter and urethra, are challenging because
      of their complexity and special milieu that gives rise to incrustation,
      inflammation and stricture formation. Tubular biohybrids were prepared from
      primary porcine smooth muscle cells embedded in a fibrin gel with a stabilising
      poly(vinylidene fluoride) mesh. A mechanotransduction was performed automatically
      with a balloon kyphoplasty catheter. Diffusion of urea and creatinine, as well as
      the bursting pressure, were measured. Light and electron microscopy were used to
      visualise cellular distribution and orientation. Histological evaluation revealed
      a uniform cellular distribution in the fibrin gel. Mechanical stimulation with a
      stretch of 20% leads to a circumferential orientation of smooth muscle cells
      inside the matrix and a longitudinal alignment on the outer surface of the
      tubular structure. Urea and creatinine permeability and bursting pressure showed
      a non-statistically significant trend towards stimulated tissue constructs. In
      this proof of concept study, an innovative technique of intraluminal pressure for
      mechanical stimulation of tubular biohybrids prepared from autologous cells and a
      composite material induce bi-directional orientation of smooth muscle cells by
      locally and cyclically applied mechanical tension. Such geometrically driven
      patterns of cell growth within a scaffold may represent a key stage in the future
      tissue engineering of implantable ureter replacements that will allow the active
      transportation of urine from the renal pelvis into the bladder.

PMID- 28750603
TI  - Evaluation of speed-accuracy trade-off in a computer task in individuals with
      cerebral palsy: a cross-sectional study.
AB  - BACKGROUND: Individuals with Cerebral Palsy (CP) present with sensorimotor
      dysfunction which make the control and execution of movements difficult. This
      study aimed to verify the speed-accuracy trade-off in individuals with CP.
      METHODS: Forty eight individuals with CP and 48 with typical development (TD)
      were evaluated (32 females and 64 males with a mean age of 15.02 +/- 6.37 years:
      minimum 7 and maximum 30 years). Participants performed the "Fitts' Reciprocal
      Aiming Task v.1.0 (Horizontal)" on a computer with different sizes and distance
      targets, composed by progressive indices of difficulty (IDs): ID2, ID4a and ID4b.
      RESULTS: There were no statistical differences between the groups in relation to
      the slope of the curve (b1) and dispersion of the movement time (r2). However,
      the intercept (b0) values presented significant differences (F(1.95) = 11.3; p =
      .001]), with greater movement time in the CP group compared to the TD group. It
      means that for individuals with CP, regardless of index difficulty, found the
      task more difficult than for TD participants. Considering CP and TD groups, speed
      accuracy trade-off was found when using different indices of difficulty (ID2 and
      ID4). However, when the same index of difficulty was used with a larger target
      and longer distance (ID4a) or with a narrow target and shorter distance (ID4b),
      only individuals with CP had more difficulty performing the tasks involving
      smaller targets. Marginally significant inverse correlations were identified
      between the values of b1 and age (r = -0.119, p = .052) and between r2 and Gross
      Motor Function Classification System (r = -0.280, p = .054), which did not occur
      with the Manual Ability Classification System. CONCLUSION: We conclude that the
      individuals with CP presented greater difficulty when the target was smaller and
      demanded more accuracy, and less difficulty when the task demanded speed. It is
      suggested that treatments should target tasks with accuracy demands, that could
      help in daily life tasks, since it is an element that is generally not considered
      by professionals during therapy. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT03002285 , retrospectively registered on 20 Dec 2016.

PMID- 28750604
TI  - Inferring Methionine Sulfoxidation and serine Phosphorylation crosstalk from
      Phylogenetic analyses.
AB  - BACKGROUND: The sulfoxidation of methionine residues within the phosphorylation
      motif of protein kinase substrates, may provide a mechanism to couple oxidative
      signals to changes in protein phosphorylation. Herein, we hypothesize that if the
      residues within a pair of phosphorylatable-sulfoxidable sites are functionally
      linked, then they might have been coevolving. To test this hypothesis a number of
      site pairs previously detected on human stress-related proteins has been
      subjected to analysis using eukaryote ortholog sequences and a phylogenetic
      approach. RESULTS: Overall, the results support the conclusion that in the
      eIF2alpha protein, serine phosphorylation at position 218 and methionine
      oxidation at position 222, belong to the same functional network. First, the
      observed data were much better fitted by Markovian models that assumed
      coevolution of both sites, with respect to their counterparts assuming
      independent evolution (p-value = 0.003). Second, this conclusion was robust with
      respect to the methods used to reconstruct the phylogenetic relationship between
      the 233 eukaryotic species analyzed. Third, the co-distribution of
      phosphorylatable and sulfoxidable residues at these positions showed multiple
      origins throughout the evolution of eukaryotes, which further supports the view
      of an adaptive value for this co-occurrence. Fourth, the possibility that the
      coevolution of these two sites might be due to structure-driven compensatory
      mutations was evaluated. The results suggested that factors other than those
      merely structural were behind the observed coevolution. Finally, the relationship
      detected between other modifiable site pairs from ataxin-2 (S814-M815), ataxin-2
      like (S211-M215) and Pumilio homolog 1 (S124-M125), reinforce the view of a role
      for phosphorylation-sulfoxidation crosstalk. CONCLUSIONS: For the four stress
      related proteins analyzed herein, their respective pairs of PTM sites
      (phosphorylatable serine and sulfoxidable methionine) were found to be evolving
      in a correlated fashion, which suggests a relevant role for methionine
      sulfoxidation and serine phosphorylation crosstalk in the control of protein
      translation under stress conditions.

PMID- 28750605
TI  - Hemodialysis patients' preferences for the management of secondary
      hyperparathyroidism.
AB  - BACKGROUND: Patient engagement and patient-centered care are critical in
      optimally managing patients with end-stage renal disease (ESRD). Understanding
      patient preferences is a key element of patient-centered care and shared decision
      making. The objective of this study was to elicit patients' preferences for the
      treatment of secondary hyperparathyroidism (SHPT) associated with ESRD using a
      discrete-choice experiment survey. METHODS: Clinical literature, nephrologist
      input, patient-education resources, and a patient focus group informed
      development of the survey instrument, which was qualitatively pretested before
      its administration to a broader sample of patients. The National Kidney
      Foundation invited individuals in the United States with ESRD who were undergoing
      hemodialysis to participate in the survey. Respondents chose among three
      hypothetical SHPT treatment alternatives (two medical alternatives and surgery)
      in each of a series of questions, which were defined by attributes of efficacy
      (effect on laboratory values and symptoms), safety, tolerability, mode of
      administration, and cost. The survey instrument included a best-worst scaling
      exercise to quantify the relative bother of the individual attributes of surgery.
      Random-parameters logit models were used to evaluate the conditional relative
      importance of the attributes. RESULTS: A total of 200 patients with ESRD
      completed the survey. The treatment attributes that were most important to the
      respondents were whether a treatment was a medication or surgery and out-of
      pocket cost. Patients had statistically significant preferences for efficacy
      attributes related to symptom management and laboratory values, but placed less
      importance on the attributes related to mode of administration and side effects.
      The most bothersome attribute of surgery was the risk of surgical mortality.
      CONCLUSIONS: Patients with ESRD and SHPT who are undergoing hemodialysis
      understand SHPT and have clear and measurable treatment preferences. These
      results may help inform clinicians about patients' preferences regarding
      treatment options for a common complication of ESRD.

PMID- 28750607
TI  - Are women with type 2 diabetes mellitus more susceptible to cardiovascular
      complications following coronary angioplasty?: a meta-analysis.
AB  - BACKGROUND: Scientific reports have shown Type 2 Diabetes Mellitus (T2DM) to be
      independently associated with adverse outcomes following Percutaneous Coronary
      Intervention (PCI). However, gender difference has also often been a
      controversial issue following PCI. Till date, very few meta-analyses have
      systematically compared the adverse cardiovascular outcomes in male versus female
      patients with T2DM following PCI. Therefore, we aimed to carry out this analysis
      in order to find out an answer to this interesting question. METHODS: Electronic
      databases were searched for English language publications reporting adverse
      cardiovascular outcomes in male versus female patients with diabetes mellitus
      respectively following coronary angioplasty. The RevMan 5.3 software was used to
      analyze selected adverse cardiovascular events whereby Odds Ratios (OR) and 95%
      Confidence Intervals (CI) were the statistical parameters. RESULTS: A total
      number of 19,304 patients with T2DM (12,986 male patients versus 6318 female
      patients) were included in this analysis. At baseline, female patients were older
      (68.7 versus 62.9 years), with a higher percentage of hypertension (75.6% versus
      66.5%) and dyslipidemia (53.3% versus 50.0%) whereas majority of the male
      patients were smokers (46.3% versus 14.9%). Results of this analysis showed short
      and long-term mortality to be significantly higher in female patients with T2DM
      (OR: 1.71, 95% CI: 1.46-2.00; P = 0.00001), and (OR: 1.20, 95% CI: 1.07-1.35; P =
      0.002) respectively. In addition, women were also more at risk for short and long
      term major adverse cardiac events (MACEs) with OR: 1.49, 95% CI: 1.07-2.07; P =
      0.02 and OR: 1.15, 95% CI: 1.04-1.28; P = 0.009 respectively. Subgroup analysis
      showed this significant result to have mainly been observed in patients with
      acute myocardial infarction compared to those with stable coronary artery
      disease. CONCLUSIONS: Following PCI, women with T2DM were indeed more susceptible
      to short and long-term cardiovascular complications compared to male patients
      with the same chronic disease. Even though this result was more applicable to
      patients with acute myocardial infarction, the fact that women were older with
      higher co-morbidities at baseline compared to men, should also not be ignored.

PMID- 28750606
TI  - Assessing the model transferability for prediction of transcription factor
      binding sites based on chromatin accessibility.
AB  - BACKGROUND: Computational prediction of transcription factor (TF) binding sites
      in different cell types is challenging. Recent technology development allows us
      to determine the genome-wide chromatin accessibility in various cellular and
      developmental contexts. The chromatin accessibility profiles provide useful
      information in prediction of TF binding events in various physiological
      conditions. Furthermore, ChIP-Seq analysis was used to determine genome-wide
      binding sites for a range of different TFs in multiple cell types. Integration of
      these two types of genomic information can improve the prediction of TF binding
      events. RESULTS: We assessed to what extent a model built upon on other TFs
      and/or other cell types could be used to predict the binding sites of TFs of
      interest. A random forest model was built using a set of cell type-independent
      features such as specific sequences recognized by the TFs and evolutionary
      conservation, as well as cell type-specific features derived from chromatin
      accessibility data. Our analysis suggested that the models learned from other TFs
      and/or cell lines performed almost as well as the model learned from the target
      TF in the cell type of interest. Interestingly, models based on multiple TFs
      performed better than single-TF models. Finally, we proposed a universal model,
      BPAC, which was generated using ChIP-Seq data from multiple TFs in various cell
      types. CONCLUSION: Integrating chromatin accessibility information with sequence
      information improves prediction of TF binding.The prediction of TF binding is
      transferable across TFs and/or cell lines suggesting there are a set of universal
      "rules". A computational tool was developed to predict TF binding sites based on
      the universal "rules".

PMID- 28750608
TI  - A comparison of the real world effectiveness of catheter ablation and drug
      therapy in atrial fibrillation patients in a Chinese setting.
AB  - BACKGROUND: Studies have demonstrated that catheter ablation of atrial
      fibrillation is associated with better rhythm control than drug therapy. The
      present study aimed to assess the clinical outcomes and health-related quality of
      life of ablation therapy in a real world setting. METHODS: A prospective, non
      randomized, single center study in a real-world clinical setting in China was
      conducted. Patients were followed up at 3, 6, and 9 months after baseline
      encounter. Propensity score matched patients receiving ablation or anti
      arrhythmic drug therapy were compared. Incidence rate of atrial fibrillation
      recurrence and quality of life outcomes were measured and analyzed using log-rank
      test, multivariate logistic regression and mixed-effects linear regression
      respectively. RESULTS: In this study, 151 atrial fibrillation patients treated by
      ablation therapy and 318 patients treated by anti-arrhythmic drugs were enrolled.
      During follow up, 82.0% in the ablation arm and 22.4% in the drug arm had no
      documented atrial fibrillation recurrence [HR for atrial fibrillation recurrence
      0.07 (95%CI: 0.02-0.21, p < 0.0001)] among paroxysmal atrial fibrillation
      patients. The corresponding no recurrent rate were 66.7% and 18.5% [0.21 (0.05
      0.95, p = 0.04)] respectively among persistent atrial fibrillation patients.
      Improvement in Short Form-36 physical component scores, Short Form-36 mental
      component scores and total Atrial Fibrillation Effect on Quality-of-life scores
      were 16.33 (14.05-18.61, p < 0.001), 8.10 (6.11-10.09, p < 0.001) and 18.28
      (16.11-20.45, p < 0.001) respectively among paroxysmal AF patients and 6.32 (3.15
      9.49, p < 0.001), 3.99 (1.82-6.16, p < 0.001) and 13.97 (10.89-17.05, p < 0.001)
      respectively among persistent AF patients. Improvements in total Atrial
      Fibrillation Effect on Quality-of-life score were also significant in ablation
      arm while no significant improvement of total Atrial Fibrillation Effect on
      Quality-of-life score in the drug arm. CONCLUSION: Compared with drug therapy,
      catheter ablation is associated with significant lower AF recurrence and improved
      overall quality of life. TRIAL REGISTRATION: The present study has been
      registered on clinicaltrials.gov. The ClinicalTrials.gov ID is NCT01878981 . The
      registration date is May 29, 2013.

PMID- 28750609
TI  - Hemodialysis patients' preferences for the management of anemia.
AB  - BACKGROUND: Patient engagement in end-stage renal disease (ESRD) is expected to
      result in a more patient-centered approach to care that aligns with patients'
      values, preferences, and goals for treatment. Nevertheless, no previous studies
      of which we are aware have evaluated patients' benefit-risk preferences for the
      management of anemia associated with ESRD. The primary objective of this study
      was to quantify the tradeoffs patients are willing to make between cardiovascular
      risks associated with some anemia medicines and red blood cell (RBC)
      transfusions. A secondary objective was to quantify the importance of avoiding
      transfusion-related risks. METHODS: A survey instrument was developed from the
      clinical literature, clinician input, patient-education resources, and a patient
      focus group. The survey instrument was qualitatively pretested before its
      administration to a broader sample of patients. The National Kidney Foundation
      invited individuals in the United States to participate in the survey. In a
      discrete-choice experiment (DCE), respondents chose between two hypothetical
      anemia medications in a series of questions. Each medication was defined by
      symptom relief, frequency of transfusions, cardiovascular risk, mode of
      administration, and out-of-pocket cost. The survey also included a best-worst
      scaling (BWS) exercise to quantify the importance of avoiding attributes of blood
      transfusions. Results from the DCE were used to estimate relative importance and
      marginal willingness to pay. Results from the BWS were converted to relative
      importance weights. RESULTS: A total of 200 individuals completed the survey.
      Patients were willing to accept a 6% medication-related risk of heart attack to
      avoid having two RBC transfusions per month. Symptom relief and mode of
      administration were of moderate importance. The most important transfusion
      related risk to avoid was transfusion-related lung injury. CONCLUSIONS: Patients
      with ESRD and anemia have measurable treatment preferences and are willing to
      accept risks associated with anemia medications to avoid transfusions.

PMID- 28750610
TI  - An exploratory study on the efficacy and safety of a BCAA preparation used in
      combination with cardiac rehabilitation for patients with chronic heart failure.
AB  - BACKGROUND: Sarcopenia is generally complicated with patients with chronic heart
      failure (CHF) and its presence negatively affects the course of heart failure,
      however effective nutritional intervention had not been elucidated yet. The
      primary objective of this study is to explore whether the addition of a branched
      chain amino acid (BCAA) preparation for cardiac rehabilitation (CR) of patients
      with CHF further improves cardiopulmonary functions, skeletal muscle functions,
      and metabolism in comparison with conventional CR. METHODS: This is a randomized,
      parallel-group comparative study. The elderly patients that were participated in
      CR and complicated with left ventricular systolic or diastolic dysfunction are
      randomized into two groups, CR + BCAA and CR. 20 weeks later, the second
      randomization is performed, which divide subjects into two groups with and
      without BCAA intervention without CR. Primary outcome measure is the rate of
      change of the anaerobic threshold workload from baseline to post-intervention.
      Secondary outcome include parameters of exercise capacity, cardiac function and
      psychological status. DISCUSSION: In the current study the effect of a promising
      new intervention, BCAA, will be assessed to determine whether its addition to CR
      improve exercise capacity in patients with heart failure, who are generally
      complicated with sarcopenia. TRIAL REGISTRATION: This clinical trial was
      registered with the University Hospital Medical Information Network-Clinical
      Trials Registry (UMIN-CTR; JPRN-UMIN R000022440 ).

PMID- 28750611
TI  - Clinical efficacy of implantation of toric intraocular lenses with different
      incision positions: a comparative study of steep-axis incision and non-steep-axis
      incision.
AB  - BACKGROUND: To compare the clinical outcomes after implantation of AcrySof Toric
      IOLs with different clear corneal incisions. METHODS: Sixty cataract patients
      with regular corneal astigmatism who underwent phacoemulsification combined with
      implantation of an AcrySof Toric IOL were enrolled. They were divided into two
      groups according to the position of the clear corneal incision: steep-axis and
      non-steep-axis. Main outcome measurements included visual acuity, residual
      astigmatism and changes of corneal astigmatism 3 months postoperatively.
      Deviation of IOL axis according to the re-calculation using the actual surgically
      induced astigmatism (SIA) and visual function 3 months after surgery were also
      evaluated. RESULTS: The corneal astigmatism decreased significantly in steep-axis
      group 3 months postoperatively (P < 0.05). Besides, more patients in non-steep
      axis group were with irregular corneal astigmatism after the surgery (43.33% vs
      10%, P = 0.004). The deviation of IOL axis according to the re-calculation using
      the actual SIA was significantly larger in non-steep-axis group than that of
      steep-axis group (P < 0.001). Moreover, the postoperative visual function was
      better in eyes of steep-axis group in various measurements, including point
      spread function, modulation transfer function and high-order aberrations.
      CONCLUSION: Steep-axis clear corneal incision could reduce the cylinder power of
      toric IOL and lower the chance of postoperative irregular astigmatism, which may
      consequently improve the postoperative visual quality.

PMID- 28750612
TI  - Causal explanations of miscarriage amongst Qataris.
AB  - BACKGROUND: Despite its commonality, there is a paucity of literature on
      miscarriage in non-Western societies. In particular, there is little
      understanding of how people ascribe cause to miscarriage. This research sought to
      gain an in-depth understanding of notions of miscarriage causality and risk
      amongst Qataris. METHODS: The study adopted an exploratory descriptive
      qualitative approach and collected data during 18 months of ethnographic research
      in Qatar, including semi-structured interviews. The sample includes 60 primary
      participants (20 pregnant women and 40 women who had recently miscarried), and 55
      secondary participants including family members, health care providers, religious
      scholars and traditional healers. Informed consent was obtained from all
      participants. Primary participants were interviewed in Arabic. The interviews
      were audio recorded, transcribed and translated into English. Data was analysed
      using an inductive thematic approach, which involved identification and
      application of multiple codes to different text segments. Data were encoded
      manually and examined for recurrences across the data set. Similar quotations
      were grouped into subcategories and further categorized into main themes.
      RESULTS: A number of key themes emerged, revealing Qatari women attributed
      miscarriages to a number of factors including: supernatural forces, such as God's
      will and evil eye; lifestyle, such as physical activities and consuming
      particular substances; medical conditions, such as diabetes; and emotional state,
      such as stress, and emotional upset. Resting, avoiding stress and upset,
      maintaining healthy diet, and spiritual healing (ruqyah) are seen as a means to
      avoid miscarriage. CONCLUSION: Practices and beliefs around miscarriage are
      embedded in social, cultural, religious and medical frameworks. Understanding the
      socio-cultural context and understandings of explanatory theories can enhance
      health care providers' understandings, resulting in improved communication and
      care.

PMID- 28750613
TI  - Transvaginal Sonography: perception and attitude of Nigerian women.
AB  - BACKGROUND: To assess the attitude to and perception of transvaginal sonography
      (TVS) among Nigerian women of mixed educational status in order to ascertain
      factors that may prevent them from submitting to TVS when recommended. METHODS: A
      Cross-sectional survey was adopted for the study. In all, one missionary, one
      government and eight private hospitals were enlisted. The instruments for data
      collection were visual analogue scale (VAS), to ascertain patients'
      pain/discomfort experience, and a researcher-developed semi-structured
      questionnaire. The level of pain/discomfort on the VAS was categorized into four
      on a scale of 100. The categories were: 0-5 (no pain), 6-40 (mild pain), 41-74
      (moderate pain), and 75-100 (severe pain). RESULTS: Majority (50.6%) of the
      respondents who attained secondary education had positive attitude to TVS. Also
      majority of the respondents (63.1%) preferred female sonographers. Majority of
      the respondents (54.1%) perceived TVS as not embarrassing, 78% did not consider
      it stressful, 96.9% reported that the sonographers were professional, 46.7% felt
      that a chaperon was needed, 98.4% reported there were enough privacy and 84.7%
      reported they needed prior information. Most of the respondents (82%) were
      willing to consent to TVS in future, 90.5% reported no pain, 8.6% reported mild
      pain/discomfort and 0.9% reported moderate pain. CONCLUSIONS: Majority of our
      respondents had positive attitude to TVS and were willing to consent to TVS in
      future, hence it was acceptable to them. It was however observed that
      acceptability increased with increasing academic status.

PMID- 28750614
TI  - Determinants of overweight with concurrent stunting among Ghanaian children.
AB  - BACKGROUND: Malnutrition (undernutrition and overnutrition) is a major public
      health problem in Ghana -affecting growth and development of individuals and the
      nation. Stunting and overweight are of particular interest, as recent national
      surveys show a rising trend of overnutrition and stubbornly high burden of
      stunting among Ghanaian children. There are currently no data on the simultaneous
      occurrence of overweight and stunting within individuals in Ghana. This paper
      presents the burden, the individual-level, and contextual determinants of
      overweight with concurrent stunting among Ghanaian children. METHODS: This study
      analyzed data set of the fourth round of the Ghana Multiple Indicator Cluster
      Survey (MICS4). Bivariate analyses were used to describe selected characteristics
      of survey respondents and their children. Hierarchical modelling approach
      facilitated identification of significant distal, intermediate and proximal
      factors/determinants of concurrent stunting and overweight. Both crude and
      adjusted prevalence ratios via a multivariable Poison regression model with their
      corresponding 95% Confidence Intervals (CI) are reported. Variables with p <=
      0.25 at the bivariate level were included in the multivariable analysis. An alpha
      value of 5% was used to indicate significance. RESULTS: Of 7550 cases (children)
      analyzed, the prevalence of stunting was 27.5%; underweight was 17.3%; and
      wasting was 7.7%. The prevalence of overweight and concurrent overweight and
      stunting were respectively 2.4% and 1.2%. Children who belonged to the fourth
      wealth quintile, were more likely to be overweight and concurrently stunted as
      against children belonging to the poorest quintile (aPR = 1.010; 95% CI, 1.003
      1.017). Compared to religious (Christians/Muslim/Traditionalist) household heads,
      children whose household heads did not belong to any religion had 2 times the
      rates of the Overweight with concurrent stunting (PR = 2.024; 95% CI, 1.016
      4.034). Children with mothers aged 20-34 and 35-49 had an increased though
      insignificant prevalence ratio of association (aPR = 1.001; 95% CI, 0.994-1.005)
      and (aPR = 1.001; 95% CI, 0.998-1.012) respectively. CONCLUSION: This analysis
      determined the prevalence of concurrent stunting and overweight among Ghanaian
      children to be 1.2%. Four contextual variables (breastfeeding status, religion,
      geographic region, and wealth index quintile) were associated with overweight
      with concurrent stunting. We conclude that, only contextual factors are
      predictive of DBM among children under five living in Ghana.

PMID- 28750615
TI  - Implications of male circumcision for women in Papua New Guinea: a
      transformational grounded theory study.
AB  - BACKGROUND: Male circumcision reduces the risk of female-to-male transmission of
      human immunodeficiency virus (HIV) and is being explored for HIV prevention in
      Papua New Guinea (PNG). PNG has a concentrated HIV epidemic which is largely
      heterosexually transmitted. There are a diverse range of male circumcision and
      penile modification practices across PNG. Exploring the implications of male
      circumcision for women in PNG is important to inform evidence-based health policy
      that will result in positive, intended consequences. METHODS: The
      transformational grounded theory study incorporated participatory action research
      and decolonizing methodologies. In Phase One, an existing data set from a male
      circumcision study of 861 male and 519 female participants was theoretically
      sampled and analyzed for women's understanding and experience of male
      circumcision. In Phase Two of the study, primary data were co-generated with 64
      women in seven interpretive focus group discussions and 11 semi-structured
      interviews to develop a theoretical model of the processes used by women to
      manage the outcomes of male circumcision. In Phase Three participants assisted to
      refine the developing transformational grounded theory and identify actions
      required to improve health. RESULTS: Many women know a lot about male
      circumcision and penile modification and the consequences for themselves, their
      families and communities. Their ability to act on this knowledge is determined by
      numerous social, cultural and economic factors. A transformational grounded
      theory was developed with connecting categories of: Women Know a Lot, Increasing
      Knowledge; Increasing Options; and Acting on Choices. Properties and dimensions
      of each category are represented in the model, along with the intervening
      condition of Safety. The condition of Safety contextualises the overarching lived
      realty for women in PNG, enables the inclusion of men in the transformational
      grounded theory model, and helps to explain relationships between men and women.
      The theory presents the core category as Power of Choice. CONCLUSIONS: This
      transformational grounded theory provides a means to explore how women experience
      male circumcision and penile modification in PNG, including for HIV prevention.
      Women who have had opportunities for education have a greater range of choices
      and an increased opportunity to act upon these choices. However, women can only
      exercise their power of choice in the context of safety. The concept of Peace
      drawn from the Social Determinants of Health is applied in order to extend the
      explanatory power of the transformational grounded theory. This study shows that
      women's ambivalence about male circumcision is often related to lack of safety, a
      consequence of gender inequality in PNG.

PMID- 28750616
TI  - Profiles of lipids, blood pressure and weight changes among premenopausal Chinese
      breast cancer patients after adjuvant chemotherapy.
AB  - BACKGROUND: Adjuvant chemotherapy improves outcome of patients with early breast
      cancer. However, chemotherapy may be associated with long term toxicities. In
      this retrospective cohort study, the objectives were to determine body weight,
      body mass index (BMI), blood pressure and fasting lipids levels of young
      premenopausal Chinese breast cancer patients after adjuvant chemotherapy.
      Potential factors associated with these parameters were identified. METHODS:
      Eligibility criteria include premenopausal Chinese patients who were diagnosed to
      have stage I-III breast cancer within 3-10 years, age < 45 and having received
      adjuvant chemotherapy at the time of breast cancer diagnosis. Information at
      initial breast cancer diagnosis were retrieved from patients' medical records and
      include age at diagnosis, tumor characteristics, anti-cancer treatments, blood
      pressure and body weight and height. At study entry, all patients had additional
      background demographics collected, as well as blood pressure, body weight and
      fasting serum lipid profiles measured. Incidence of chemotherapy-related
      amenorrhoea (CRA) and menopause were determined. Factors associated with weight
      gain, hypertension and dyslipidaemias were analyzed. RESULTS: Two hundred and
      eighty patients were studied. The median age at breast cancer diagnosis was 41
      years (range: 24-45). The median time from breast cancer diagnosis to study entry
      was 5.0 years. The median age at study entry was 46.5 years (range: 28-54). 91.1%
      developed CRA; 48.9% had become menopausal and 10% were peri-menopausal. Between
      initial breast cancer diagnosis and the time of study entry, the median weight
      gain was 1.8 kg; 63.2% gained weight by >2%; 52.1% were overweight/obese; 30.7%
      had hypertension. Abnormal total-cholesterol and LDL-cholesterol occurred in
      34.3% and 56.1% respectively. On multivariate analyses, older age was associated
      with reduced risk while occurrence of CRA and having received taxane-containing
      regimens were associated with increased risk of weight gain. Oestrogen-receptor
      positivity was associated with reduced risk while overweight/obese statuses were
      associated with increased risk of hypertension. Use of tamoxifen was associated
      with reduced risk of abnormal LDL-cholesterol. Weight gain, overweight/obese,
      older age, progression to post/peri-menopausal status at study entry, having
      received corticosteroid premedication before adjuvant chemotherapy and having
      received taxane-containing adjuvant chemotherapy were associated with increased
      risk of dyslipidaemias. CONCLUSION: Among young premenopausal Chinese breast
      cancer patients who had received adjuvant chemotherapy, the current study has
      revealed that although there was only a median weight gain of 1.8 kg, there was a
      nearly 60% increase in abnormal BMI. Further, a significant proportion of
      patients were detected to have hypertension and dyslipidaemias. Interventional
      studies with lifestyle modifications are warranted.

PMID- 28750617
TI  - Health system preparedness for integration of mental health services in rural
      Liberia.
AB  - BACKGROUND: There are increasing efforts and attention focused on the delivery of
      mental health services in primary care in low resource settings (e.g., mental
      health Gap Action Programme, mhGAP). However, less attention is devoted to
      systematic approaches that identify and address barriers to the development and
      uptake of mental health services within primary care in low-resource settings.
      Our objective was to prepare for optimal uptake by identifying barriers in rural
      Liberia. The country's need for mental health services is compounded by a 14-year
      history of political violence and the largest Ebola virus disease outbreak in
      history. Both events have immediate and lasting mental health effects. METHODS: A
      mixed-methods approach was employed, consisting of qualitative interviews with 22
      key informants and six focus group discussions. Additional qualitative data as
      well as quantitative data were collected through semi-structured assessments of
      19 rural primary care health facilities. Data were collected from March 2013 to
      March 2014. RESULTS: Potential barriers to development and uptake of mental
      health services included lack of mental health knowledge among primary health
      care staff; high workload for primary health care workers precluding addition of
      mental health responsibilities; lack of mental health drugs; poor physical
      infrastructure of health facilities including lack of space for confidential
      consultation; poor communication support including lack of electricity and mobile
      phone networks that prevent referrals and phone consultation with supervisors;
      absence of transportation for patients to facilitate referrals; negative
      attitudes and stigma towards people with severe mental disorders and their family
      members; and stigma against mental health workers. CONCLUSIONS: To develop and
      facilitate effective primary care mental health services in a post-conflict, low
      resource setting will require (1) addressing the knowledge and clinical skills
      gap in the primary care workforce; (2) improving physical infrastructure of
      health facilities at care delivery points; and (3) implementing concurrent
      interventions designed to improve attitudes towards people with mental illness,
      their family members and mental health care providers.

PMID- 28750618
TI  - Difference in the functional connectivity of the dorsolateral prefrontal cortex
      between smokers with nicotine dependence and individuals with internet gaming
      disorder.
AB  - BACKGROUND: It has been reported that internet gaming disorder (IGD) and smokers
      with nicotine dependence (SND) share clinical characteristics, such as over
      engagement despite negative consequences and cravings. This study is to
      investigate the alterations in the resting-state functional connectivity (rsFC)
      of the dorsolateral prefrontal cortex (DLPFC) observed in SND and IGD. In this
      study, 27 IGD, 29 SND, and 33 healthy controls (HC) underwent a resting-state
      functional magnetic resonance imaging (rs-fMRI) scan. DLPFC connectivity was
      determined in all participates by investigating the synchronized low-frequency
      fMRI signal fluctuations using a temporal seed-based correlation method. RESULTS:
      Compared with the HC group, the IGD and SND groups showed decreased rsFC with
      DLPFC in the right insula and left inferior frontal gyrus with DLPFC. Compared
      with SND group, the IGD subjects exhibited increased rsFC in the left inferior
      temporal gyrus and right inferior orbital frontal gyrus and decreased rsFC in the
      right middle occipital gyrus, supramarginal gyrus, and cuneus with DLPFC.
      CONCLUSION: Our results confirmed that SND and IGD share similar neural
      mechanisms related to craving and impulsive inhibitions. The significant
      difference in rsFC with DLPFC between the IGD and SND subjects may be attributed
      to the visual and auditory stimulation generated by long-term internet gaming.

PMID- 28750619
TI  - The practical use of genome sequencing data in the management of a feline colony
      pedigree.
AB  - BACKGROUND: A higher prevalence of inherited disorders among companion animals
      are often rooted in their historical restricted artificial selection for a
      variety of observed phenotypes that eventually decreased genetic diversity. Cats
      have been afflicted with many inherited diseases due to domestication and intense
      breed selection. Advances in sequencing technology have generated a more
      comprehensive way to access genetic information from an individual, allowing
      identification of putative disease-causing variants and in practice a means to
      avoid their spread and thus better pedigree management. We examine variants in
      three domestic shorthair cats and then calculated overall genetic diversity to
      extrapolate the benefits of this data for breeding programs within a feline
      colony. RESULTS: We generated whole genome sequence (WGS) data for three related
      cats that belong to a large feline pedigree colony. Genome-wide coverage ranged
      from 27-32X, from which we identified 18 million variants in total. Previously
      known disease-causing variants were screened in our cats, but none carry any of
      these known disease alleles. Loss of function (LoF) variants, that are in genes
      associated with a detrimental phenotype in human or mice were chosen for further
      evaluation on the comparative impact inferred. A set of LoF variants were
      observed in four genes, each with predicted detrimental phenotypes as a result.
      However, none of our cats displayed the expected disease phenotypes. Inbreeding
      coefficients and runs of homozygosity were also evaluated as a measure of genetic
      diversity. We find low inbreeding coefficients and total runs of homozygosity,
      thus suggesting pedigree management of genetic relatedness is acceptable.
      CONCLUSIONS: The use of WGS of a small sampling among a large feline colony has
      enabled us to identify possible disease-causing variants, their genotype state
      and measure pedigree management of genetic diversity. We contend a limited but
      strategic sampling of feline colony individuals using WGS can inform
      veterinarians of future health anomalies and guide breeding practices to ensure
      healthy genetic diversity.

PMID- 28750620
TI  - Efficacy of commercialised extracorporeal shock wave lithotripsy service: a
      review of 589 renal stones.
AB  - BACKGROUND: Extracorporeal shockwave lithotripsy (ESWL) is the management of
      choice for renal stones 20 mm or smaller, with a stone clearance rate of up to
      89%. The purpose of the present is to investigate the efficacy of a
      commercialised ESWL service, being performed as an outsourced treatment using a
      mobile lithotripsy system on an outpatient basis. Furthermore, the study aims to
      evaluate the risk of needing treatment with an internal ureteral double-J stent
      (JJ) after ESWL treatment. METHODS: During an eight-year period, 461 patients
      with a total of 589 renal stones were treated using a mobile lithotripsy system
      at a single Danish institution. A commercial company performed all treatments
      using a Storz Modulith SLK(r) system. Each stone was prospectively registered
      according to size, intra renal location and the presence of a JJ at the time of
      treatment. The number of required ESWL treatments and auxiliary procedures were
      retrospectively evaluated. RESULTS: The success rate after the initial ESWL
      procedure was 69%, which increased to an overall success rate of 93% after
      repeated treatment. A negative correlation was found between stone size and the
      overall success rate (r = -0.2, p < 0.01). The upper calyx was associated with a
      significantly better success rate, but otherwise intra renal stone location was
      not predictive for treatment success. A total of 17 patients (2.9%) required
      treatment with a JJ after the ESWL procedure. No significant difference was
      observed between the stone size or intra renal location and the risk of needing
      treatment with JJ after ESWL. CONCLUSIONS: Commercialised ESWL treatment can
      achieve an overall success rate of more than 90% using a mobile lithotripsy
      system. As expected, an inverse relation between stone size and success rate was
      found. Patients who do not require treatment with a JJ prior to ESWL will only
      rarely need treatment with a JJ after ESWL, irrespective of stone size and intra
      renal stone location.

PMID- 28750621
TI  - Clinical and electrophysiological features of post-traumatic Guillain-Barre
      syndrome.
AB  - BACKGROUND: Post-traumatic Guillain-Barre syndrome (GBS) is a rarely described
      potentially life-threatening cause of weakness. We sought to elucidate the
      clinical features and electrophysiological patterns of post-traumatic GBS as an
      aid to diagnosis. METHODS: We retrospectively studied six patients diagnosed with
      post-traumatic GBS between 2014 and 2016 at Tianjin Medical University General
      Hospital, China. Clinical features, serum analysis, lumbar puncture results,
      electrophysiological examinations, and prognosis were assessed. RESULTS: All six
      patients had different degrees of muscular atrophy at nadir and in two,
      respiratory muscles were involved. Five also had damaged cranial nerves and four
      of these had serum antibodies against gangliosides. The most common
      electrophysiological findings were relatively normal distal latency, prominent
      reduction of compound muscle action potential amplitude, and absence of F-waves,
      which are consistent with an axonal form of GBS. CONCLUSIONS: It is often
      overlooked that GBS can be triggered by non-infectious factors such as trauma and
      its short-term prognosis is poor. Therefore, it is important to analyze the
      clinical and electrophysiological features of GBS after trauma. Here we have
      shown that electrophysiological evaluations are helpful for diagnosing post
      traumatic GBS. Early diagnosis may support appropriate treatment to help prevent
      morbidity and improve prognosis.

PMID- 28750622
TI  - Re-classification within the serogroups O3 and O8 of Citrobacter strains.
AB  - BACKGROUND: Citrobacter strains are opportunistic pathogens often responsible for
      serious enteric as well as extra-intestinal diseases, and therefore the O
      antigenic scheme, still in use in diagnostic identification, should be set for
      proper serotyping. The structures of more than 30 different Citrobacter O
      antigens (O-polysaccharide chains of the lipopolysaccharides) of 43 Citrobacter O
      serogroups have been elucidated so far. However, relationships between strains in
      several heterogeneous serogroups still need to be clarified by immunochemical
      studies. These include complex serogroups O3 and O8, represented by 20 and 7
      strains, respectively, which are the subject of the present work. Earlier, the O
      polysaccharide structures have been determined for Citrobacter O3 strain Be35/57
      (PCM 1508) and Citrobacter O8 strain Be64/57 (PCM 1536). RESULTS: Serological
      studies (immunoblotting) carried out on Citrobacter lipopolysaccharides from
      different strains ascribed to serogroups O3 and O8 showed that each of these
      serogroups should be divided into non-cross-reacting subgroups. Based on the
      results of chemical analyses and 1H and 13C NMR spectroscopy the structure of
      Citrobacter O-antigens from strains PCM 1504 (O6) and PCM 1573 (O2) have been
      established. Chemical data combined with serological analyses showed that several
      Citrobacter strains should be reclassified into other serogroups. CONCLUSIONS:
      Immunochemical studies carried out on Citrobacter LPS, described in this paper,
      showed the expediency of reclassification of: 1) strains PCM 1504 and PCM 1573
      from serogroups O6 and O2 to serogroups O3 and O8, respectively, 2) strains PCM
      1503 and PCM 1505 from serogroups O3 and O8 to new serogroups O3a and O8a,
      respectively.

PMID- 28750623
TI  - l1kdeconv: an R package for peak calling analysis with LINCS L1000 data.
AB  - BACKGROUND: LINCS L1000 is a high-throughput technology that allows gene
      expression measurement in a large number of assays. However, to fit the
      measurements of ~1000 genes in the ~500 color channels of LINCS L1000, every two
      landmark genes are designed to share a single channel. Thus, a deconvolution step
      is required to infer the expression values of each gene. Any errors in this step
      can be propagated adversely to the downstream analyses. RESULTS: We presented a
      LINCS L1000 data peak calling R package l1kdeconv based on a new outlier
      detection method and an aggregate Gaussian mixture model (AGMM). Upon the remove
      of outliers and the borrowing information among similar samples, l1kdeconv showed
      more stable and better performance than methods commonly used in LINCS L1000 data
      deconvolution. CONCLUSIONS: Based on the benchmark using both simulated data and
      real data, the l1kdeconv package achieved more stable results than the commonly
      used LINCS L1000 data deconvolution methods.

PMID- 28750624
TI  - Leptin OB3 peptide suppresses leptin-induced signaling and progression in ovarian
      cancer cells.
AB  - BACKGROUND: Obesity and its comorbidities constitute a serious health burden
      worldwide. Leptin plays an important role in diet control; however, it has a
      stimulatory potential on cancer cell proliferation. The OB3 peptide, a synthetic
      peptide, was shown to be more active than leptin in regulating metabolism but
      with no mitogenic effects in cancer cells. METHODS: In this study, we
      investigated the proliferative effects, gene expressions and signaling pathways
      modulated by leptin and OB3 in human ovarian cancer cells. In addition, an animal
      study was performed. RESULTS: Leptin, but not OB3, induced the proliferation of
      ovarian cancer cells. Interestingly, OB3 blocked the leptin-induced proliferative
      effect when it was co-applied with leptin. Both leptin and OB3 activated the
      phosphatidylinositol-3-kinase (PI3K) signal transduction pathway. In addition,
      leptin stimulated the phosphorylation of signal transducer and activator of
      transcription-3 (STAT3) Tyr-705 as well as estrogen receptor (ER)alpha, and the
      expression of ERalpha-responsive genes. Interestingly, all leptin-induced signal
      activation and gene expressions were blocked by the co-incubation with OB3 and
      the inhibition of extracellular signal-regulated kinase (ERK)1/2. Coincidently,
      leptin, but not OB3, increased circulating levels of follicle-stimulating hormone
      (FSH) which is known to play important roles in the initiation and proliferation
      of ovarian cancer cells. CONCLUSIONS: In summary, our findings suggest that the
      OB3 peptide may prevent leptin-induced ovarian cancer initiation and progression
      by disrupting leptin-induced proliferative signals via STAT3 phosphorylation and
      ERalpha activation. Therefore, the OB3 peptide is a potential anticancer agent
      that might be employed to prevent leptin-induced cancers in obese people.

PMID- 28750625
TI  - Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds.
AB  - BACKGROUND: To date, genome-scale analyses in the domestic horse have been
      limited by suboptimal single nucleotide polymorphism (SNP) density and uneven
      genomic coverage of the current SNP genotyping arrays. The recent availability of
      whole genome sequences has created the opportunity to develop a next generation,
      high-density equine SNP array. RESULTS: Using whole genome sequence from 153
      individuals representing 24 distinct breeds collated by the equine genomics
      community, we cataloged over 23 million de novo discovered genetic variants.
      Leveraging genotype data from individuals with both whole genome sequence, and
      genotypes from lower-density, legacy SNP arrays, a subset of ~5 million high
      quality, high-density array candidate SNPs were selected based on breed
      representation and uniform spacing across the genome. Considering probe design
      recommendations from a commercial vendor (Affymetrix, now Thermo Fisher
      Scientific) a set of ~2 million SNPs were selected for a next-generation high
      density SNP chip (MNEc2M). Genotype data were generated using the MNEc2M array
      from a cohort of 332 horses from 20 breeds and a lower-density array, consisting
      of ~670 thousand SNPs (MNEc670k), was designed for genotype imputation.
      CONCLUSIONS: Here, we document the steps taken to design both the MNEc2M and
      MNEc670k arrays, report genomic and technical properties of these genotyping
      platforms, and demonstrate the imputation capabilities of these tools for the
      domestic horse.

PMID- 28750626
TI  - Biogeographical distribution analysis of hydrocarbon degrading and biosurfactant
      producing genes suggests that near-equatorial biomes have higher abundance of
      genes with potential for bioremediation.
AB  - BACKGROUND: Bacterial and Archaeal communities have a complex, symbiotic role in
      crude oil bioremediation. Their biosurfactants and degradation enzymes have been
      in the spotlight, mainly due to the awareness of ecosystem pollution caused by
      crude oil accidents and their use. Initially, the scientific community studied
      the role of individual microbial species by characterizing and optimizing their
      biosurfactant and oil degradation genes, studying their individual distribution.
      However, with the advances in genomics, in particular with the use of New
      Generation-Sequencing and Metagenomics, it is now possible to have a macro view
      of the complex pathways related to the symbiotic degradation of hydrocarbons and
      surfactant production. It is now possible, although more challenging, to obtain
      the DNA information of an entire microbial community before automatically
      characterizing it. By characterizing and understanding the interconnected role of
      microorganisms and the role of degradation and biosurfactant genes in an
      ecosystem, it becomes possible to develop new biotechnological approaches for
      bioremediation use. This paper analyzes 46 different metagenome samples, spanning
      20 biomes from different geographies obtained from different research projects.
      RESULTS: A metagenomics bioinformatics pipeline, focused on the biodegradation
      and biosurfactant-production pathways, genes and organisms, was applied. Our main
      results show that: (1) surfactation and degradation are correlated events, and
      therefore should be studied together; (2) terrestrial biomes present more
      degradation genes, especially cyclic compounds, and less surfactation genes, when
      compared to water biomes; and (3) latitude has a significant influence on the
      diversity of genes involved in biodegradation and biosurfactant production. This
      suggests that microbiomes found near the equator are richer in genes that have a
      role in these processes and thus have a higher biotechnological potential.
      CONCLUSION: In this work we have focused on the biogeographical distribution of
      hydrocarbon degrading and biosurfactant producing genes. Our principle results
      can be seen as an important step forward in the application of bioremediation
      techniques, by considering the biostimulation, optimization or manipulation of a
      starting microbial consortia from the areas with higher degradation and
      biosurfactant producing genetic diversity.

PMID- 28750627
TI  - Air pollution exposure is associated with MRSA acquisition in young U.S. children
      with cystic fibrosis.
AB  - BACKGROUND: The role of air pollution in increasing susceptibility to respiratory
      tract infections in the cystic fibrosis (CF) population has not been well
      described. We recently demonstrated that chronic PM2.5 exposure is associated
      with an increased risk of initial Pseudomonas aeruginosa acquisition in young
      children with CF. The purpose of this study was to determine whether PM2.5
      exposure is a risk factor for acquisition of other respiratory pathogens in young
      children with CF. METHODS: We conducted a retrospective study of initial
      acquisition of methicillin susceptible and methicillin resistant Staphylococcus
      aureus (MSSA and MRSA), Stenotrophomonas maltophilia and Achromobacter
      xylosoxidans in U.S. children <6 years of age with CF using the CF Foundation
      Patient Registry, 2003-2009. Multivariable Weibull regression with interval
      censored outcomes was used to evaluate the association of PM2.5 concentration in
      the year prior to birth and risk of acquisition of each organism. RESULTS: During
      follow-up 63%, 17%, 24%, and 5% of children acquired MSSA, MRSA, S. maltophilia,
      and A. xylosoxidans, respectively. A 10 MUg/m3 increase in PM2.5 exposure was
      associated with a 68% increased risk of MRSA acquisition (Hazard Ratio: 1.68; 95%
      Confidence Interval: 1.24, 2.27). PM2.5 was not associated with acquisition of
      other respiratory pathogens. CONCLUSIONS: Fine particulate matter is an
      independent risk factor for initial MRSA acquisition in young children with CF.
      These results support the increasing evidence that air pollution contributes to
      pulmonary morbidities in the CF community.

PMID- 28750628
TI  - What works for whom in the management of diabetes in people living with dementia:
      a realist review.
AB  - BACKGROUND: Dementia and diabetes mellitus are common long-term conditions and co
      exist in a large number of older people. People living with dementia (PLWD) may
      be less able to manage their diabetes, putting them at increased risk of
      complications such as hypoglycaemia. The aim of this review was to identify key
      mechanisms within different interventions that are likely to improve diabetes
      outcomes in PLWD. METHODS: This is a realist review involving scoping of the
      literature and stakeholder interviews to develop theoretical explanations of how
      interventions might work, systematic searches of the evidence to test and develop
      the theories and their validation with a purposive sample of stakeholders. Twenty
      six stakeholders - user/patient representatives, dementia care providers,
      clinicians specialising in diabetes or dementia and researchers - took part in
      interviews, and 24 participated in a consensus conference. RESULTS: We included
      89 papers. Ten focused on PLWD and diabetes, and the remainder related to people
      with either dementia, diabetes or other long-term conditions. We identified six
      context-mechanism-outcome configurations which provide an explanatory account of
      how interventions might work to improve the management of diabetes in PLWD. This
      includes embedding positive attitudes towards PLWD, person-centred approaches to
      care planning, developing skills to provide tailored and flexible care, regular
      contact, family engagement and usability of assistive devices. An overarching
      contingency emerged concerning the synergy between an intervention strategy, the
      dementia trajectory and social and environmental factors, especially family
      involvement. CONCLUSIONS: Evidence highlighted the need for personalised care,
      continuity and family-centred approaches, although there was limited evidence
      that this happens routinely. This review suggests there is a need for a flexible
      service model that prioritises quality of life, independence and patient and
      carer priorities. Future research on the management of diabetes in older people
      with complex health needs, including those with dementia, needs to look at how
      organisational structures and workforce development can be better aligned to
      their needs. TRIAL REGISTRATION: PROSPERO, CRD42015020625. Registered on 18 May
      2015.

PMID- 28750630
TI  - Conjunctival lymphoma during pregnancy: a case report.
AB  - BACKGROUND: To present a case of conjunctival lymphoma in a young woman
      complicated by pregnancy. CASE PRESENTATION: A 38-year-old previously healthy
      woman presented with a 2-year history of progressive right blepharoptosis. Giant
      papillomatous sessile masses were identified in the upper and lower fornix
      bilaterally and involved the tarsus of the right upper lid. The remaining
      ophthalmic examination was unremarkable. Histopathology and immunohistochemistry
      showed mucosa-associated lymphoid tissue (MALT) lymphoma with immunoglobulin
      kappa monotype. Further workup showed no evidence of systemic lymphoma or orbital
      involvement. CONCLUSIONS: Partial regrowth of conjunctival lymphoma occurred 6
      months after excision and the MALT lymphoma remained indolent during the course
      of her pregnancy without radiotherapy.

PMID- 28750629
TI  - Role of free fatty acids in endothelial dysfunction.
AB  - Plasma free fatty acids levels are increased in subjects with obesity and type 2
      diabetes, playing detrimental roles in the pathogenesis of atherosclerosis and
      cardiovascular diseases. Increasing evidence showing that dysfunction of the
      vascular endothelium, the inner lining of the blood vessels, is the key player in
      the pathogenesis of atherosclerosis. In this review, we aimed to summarize the
      roles and the underlying mechanisms using the evidence collected from clinical
      and experimental studies about free fatty acid-mediated endothelial dysfunction.
      Because of the multifaceted roles of plasma free fatty acids in mediating
      endothelial dysfunction, elevated free fatty acid level is now considered as an
      important link in the onset of endothelial dysfunction due to metabolic syndromes
      such as diabetes and obesity. Free fatty acid-mediated endothelial dysfunction
      involves several mechanisms including impaired insulin signaling and nitric oxide
      production, oxidative stress, inflammation and the activation of the renin
      angiotensin system and apoptosis in the endothelial cells. Therefore, targeting
      the signaling pathways involved in free fatty acid-induced endothelial
      dysfunction could serve as a preventive approach to protect against the
      occurrence of endothelial dysfunction and the subsequent complications such as
      atherosclerosis.

PMID- 28750631
TI  - Music interventions to reduce stress and anxiety in pregnancy: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Stress and anxiety are common in pregnancy and shown to have adverse
      effects on maternal and infant health outcomes. The aim of this review and meta
      analysis was to assess the effectiveness of music-based interventions in reducing
      levels of stress or anxiety among pregnant women. METHODS: Six databases were
      searched using key terms relating to pregnancy, psychological stress, anxiety and
      music. Inclusion criteria were randomised controlled or quasi-experimental trials
      that assessed the effect of music during pregnancy and measured levels of
      psychological stress or anxiety as a primary or secondary outcome. Two authors
      independently assessed and extracted data. Quality assessment was performed using
      The Cochrane Collaboration risk of bias criteria. Meta-analyses were conducted to
      assess stress and anxiety reduction following a music-based intervention compared
      to a control group that received routine antenatal care. RESULTS: Five studies
      with 1261 women were included. Music interventions significantly reduced levels
      of maternal anxiety (Standardised Mean Difference (SMD): -0.21; 95% Confidence
      Interval (CI) -0.39, -0.03; p = 0.02). There was no significant effect on general
      stress (SMD: -0.08; 95% CI -0.25, 0.09; p = 0.35) or pregnancy-specific stress
      (SMD: -0.02; 95% CI -0.19, 0.15; p = 0.80). The methodological quality of
      included studies was moderate to weak, all studies having a high or unclear risk
      of bias in allocation concealment, blinding and selective outcome reporting.
      CONCLUSIONS: There is evidence that music-based interventions may reduce anxiety
      in pregnancy; however, the methodological quality of the studies was moderate to
      weak. Additional research is warranted focusing on rigour of assessment,
      intensity of interventions delivered and methodological limitations.

PMID- 28750632
TI  - Impact of bileaflet mitral valve prolapse on quantification of mitral
      regurgitation with cardiac magnetic resonance: a single-center study.
AB  - BACKGROUND: To quantify mitral regurgitation (MR) with CMR, the regurgitant
      volume can be calculated as the difference between the left ventricular (LV)
      stroke volume (SV) measured with the Simpson's method and the reference SV, i.e.
      the right ventricular SV (RVSV) in patients without tricuspid regurgitation.
      However, for patients with prominent mitral valve prolapse (MVP), the Simpson's
      method may underestimate the LV end-systolic volume (LVESV) as it only considers
      the volume located between the apex and the mitral annulus, and neglects the
      ventricular volume that is displaced into the left atrium but contained within
      the prolapsed mitral leaflets at end systole. This may lead to an underestimation
      of LVESV, and resulting an over-estimation of LVSV, and an over-estimation of
      mitral regurgitation. The aim of the present study was to assess the impact of
      prominent MVP on MR quantification by CMR. METHODS: In patients with MVP (and no
      more than trace tricuspid regurgitation) MR was quantified by calculating the
      regurgitant volume as the difference between LVSV and RVSV. LVSVuncorr was
      calculated conventionally as LV end-diastolic (LVEDV) minus LVESV. A corrected
      LVESVcorr was calculated as the LVESV plus the prolapsed volume, i.e. the volume
      between the mitral annulus and the prolapsing mitral leaflets. The 2 methods were
      compared with respect to the MR grading. MR grades were defined as absent or
      trace, mild (5-29% regurgitant fraction (RF)), moderate (30-49% RF), or severe
      (>=50% RF). RESULTS: In 35 patients (44.0 +/- 23.0y, 14 males, 20 patients with
      MR) the prolapsed volume was 16.5 +/- 8.7 ml. The 2 methods were concordant in
      only 12 (34%) patients, as the uncorrected method indicated a 1-grade higher MR
      severity in 23 (66%) patients. For the uncorrected/corrected method, the
      distribution of the MR grades as absent-trace (0 vs 11, respectively), mild (20
      vs 18, respectively), moderate (11 vs 5, respectively), and severe (4 vs 1,
      respectively) was significantly different (p < 0.001). In the subgroup without
      MR, LVSVcorr was not significantly different from RVSV (difference: 2.5 +/- 4.7
      ml, p = 0.11 vs 0) while a systematic overestimation was observed with LVSVuncorr
      (difference: 16.9 +/- 9.1 ml, p = 0.0007 vs 0). Also, RVSV was highly correlated
      with aortic forward flow (n = 24, R 2 = 0.97, p < 0.001). CONCLUSION: For
      patients with severe bileaflet prolapse, the correction of the LVSV for the
      prolapse volume is suggested as it modified the assessment of MR severity by one
      grade in a large portion of patients.

PMID- 28750633
TI  - Urinary bisphenol A and pubertal development in Chinese school-aged girls: a
      cross-sectional study.
AB  - BACKGROUND: Animal studies suggest that bisphenol A (BPA) may perturb pubertal
      development in females. However, evidence from human studies is limited. METHODS:
      This was a cross-sectional study to investigate the association between BPA
      exposure and pubertal development in school-aged girls. A total of 655 girls aged
      9-18 years were selected from three schools in Shanghai, from May to June 2011.
      We collected one single spot urine sample from each girl. Urine BPA
      concentrations were measured by modified high-performance liquid chromatography
      and categorized according to LOD and the median of those above LOD. Pubertal
      development status was assessed by using Tanner staging, and age at menarche was
      collected as a milestone for mid-puberty. Modified Poisson regression was used to
      estimate adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs).
      RESULTS: After adjustment for potential confounders, girls with detected BPA were
      more likely to have delayed menarche, a mid-puberty event, compared with girls
      with undetectable BPA; the prevalence ratios (PR) were 0.73 (0.56, 0.95) for
      those with moderate BPA(LOD-median) and 0.72 (0.52, 0.99) for those with high
      BPA(>median), respectively. Girls aged 9-12 years with detected BPA were more
      likely to have reached pubic hair stage 2, the indicator of pubarche; while among
      girls aged >15 years, those with detected BPA were less likely to have reached
      pubic hair stage 5, the late stage of pubic hair development. CONCLUSIONS: BPA
      exposure was associated with alterations in the timing of pubertal development.
      Results in the present study should be interpreted with caution because of its
      cross-sectional nature and the limited sample size in each age group.

PMID- 28750634
TI  - Preclinical carotid atherosclerosis in patients with latent autoimmune diabetes
      in adults (LADA), type 2 diabetes and classical type 1 diabetes.
AB  - BACKGROUND: LADA is probably the most prevalent form of autoimmune diabetes.
      Nevertheless, there are few data about cardiovascular disease in this group of
      patients. The aim of this study was to investigate the frequency of carotid
      atherosclerotic plaques in patients with LADA as compared with patients with
      classic type 1 diabetes and type 2 diabetes. METHODS: Patients with LADA were
      matched for age and gender in different proportions to patients with type 2
      diabetes, and classic type 1 diabetes. None of the patients had clinical
      cardiovascular disease. All subjects underwent B-mode carotid ultrasound to
      detect atheroma plaques. Demographics were obtained from all subjects. RESULTS:
      We included 71 patients with LADA, 191 patients with type 2 diabetes and 116
      patients with type 1 diabetes. Carotid atherosclerosis was more frequent in
      patients with LADA compared with type 2 diabetes (73.2% vs. 56.9%, P = 0.0018)
      and classic type 1 diabetes (57.1%, P = 0.026); these changes occurred despite
      healthier macrovascular risk profiles in the former. Age (P < 0.001), smoking (P
      = 0.003) and hypertension (P = 0.019) were independently associated with carotid
      atherosclerosis. Multiple plaques were also more frequent in patients with LADA
      as compared with classic type 1 diabetes and type 2 diabetes (45.1% and 33.6% vs.
      27.2%, respectively, P = 0.022). The frequency of carotid plaques increased with
      increasing diabetes duration in LADA patients compared with type 2 diabetes
      (85.7% vs. 58.8%, inverse OR 5.72 [1.5-21.8]; P = 0.009). CONCLUSIONS: LADA
      patients do not present with less carotid atherosclerosis than patients with type
      1 and type 2 diabetes. Their macrovascular risk occurs despite a healthier
      macrovascular risk profile than those patients with type 2 diabetes.

PMID- 28750635
TI  - Proteomic analysis of human follicular fluid associated with successful in vitro
      fertilization.
AB  - BACKGROUND: Human follicular fluid (HFF) provides a key environment for follicle
      development and oocyte maturation, and contributes to oocyte quality and in vitro
      fertilization (IVF) outcome. METHODS: To better understand folliculogenesis in
      the ovary, a proteomic strategy based on dual reverse phase high performance
      liquid chromatography (RP-HPLC) coupled to matrix-assisted laser
      desorption/ionization time-of-flight tandem mass spectrometry (LC-MALDI TOF/TOF
      MS) was used to investigate the protein profile of HFF from women undergoing
      successful IVF. RESULTS: A total of 219 unique high-confidence (False Discovery
      Rate (FDR) < 0.01) HFF proteins were identified by searching the reviewed Swiss
      Prot human database (20,183 sequences), and MS data were further verified by
      western blot. PANTHER showed HFF proteins were involved in complement and
      coagulation cascade, growth factor and hormone, immunity, and transportation,
      KEGG indicated their pathway, and STRING demonstrated their interaction networks.
      In comparison, 32% and 50% of proteins have not been reported in previous human
      follicular fluid and plasma. CONCLUSIONS: Our HFF proteome research provided a
      new complementary high-confidence dataset of folliculogenesis and oocyte
      maturation environment. Those proteins associated with innate immunity,
      complement cascade, blood coagulation, and angiogenesis might serve as the
      biomarkers of female infertility and IVF outcome, and their pathways facilitated
      a complete exhibition of reproductive process.

PMID- 28750636
TI  - Pathogenic genotype of major piroplasm surface protein associated with anemia in
      Theileria orientalis infection in cattle.
AB  - Serious disease outbreaks in cattle caused by Theileria orientalis have emerged
      in the Asia-Pacific region. Genetic variables of the major piroplasm surface
      protein (MPSP) expressed on the surface of the piroplasm inside T. orientalis
      infected erythrocytes are considered to be associated with variation in the
      pathogenicity of T. orientalis. Our study describes the clinically relevant MPSP
      types associated with anemia in Theileria-infected cattle. These results revealed
      that MPSP expression plays an important role in hematological alterations in
      Theileria-infected cattle, and that MPSP type 1 is strongly associated with
      bovine anemia, which can be a potential target for the prevention of bovine
      theileriosis.

PMID- 28750637
TI  - Quantification of myocardium at risk in ST- elevation myocardial infarction: a
      comparison of contrast-enhanced steady-state free precession cine cardiovascular
      magnetic resonance with coronary angiographic jeopardy scores.
AB  - BACKGROUND: Clinical outcome following acute myocardial infarction is predicted
      by final infarct size evaluated in relation to left ventricular myocardium at
      risk (MaR). Contrast-enhanced steady-state free precession (CE-SSFP)
      cardiovascular magnetic resonance imaging (CMR) is not widely used for assessing
      MaR. Evidence of its utility compared to traditional assessment methods and as a
      surrogate for clinical outcome is needed. METHODS: Retrospective analysis within
      a study evaluating post-conditioning during ST elevation myocardial infarction
      (STEMI) treated with coronary intervention (n = 78). CE-SSFP post-infarction was
      compared with angiographic jeopardy methods. Differences and variability between
      CMR and angiographic methods using Bland-Altman analyses were evaluated. Clinical
      outcomes were compared to MaR and extent of infarction. RESULTS: MaR showed
      correlation between CE-SSFP, and both BARI and APPROACH scores of 0.83 (p <
      0.0001) and 0.84 (p < 0.0001) respectively. Bias between CE-SSFP and BARI was
      1.1% (agreement limits -11.4 to +9.1). Bias between CE-SSFP and APPROACH was 1.2%
      (agreement limits -13 to +10.5). Inter-observer variability for the BARI score
      was 0.56 +/- 2.9; 0.42 +/- 2.1 for the APPROACH score; -1.4 +/- 3.1% for CE-SSFP.
      Intra-observer variability was 0.15 +/- 1.85 for the BARI score; for the APPROACH
      score 0.19 +/- 1.6; and for CE-SSFP -0.58 +/- 2.9%. CONCLUSION: Quantification of
      MaR with CE-SSFP imaging following STEMI shows high correlation and low bias
      compared with angiographic scoring and supports its use as a reliable and
      practical method to determine myocardial salvage in this patient population.
      TRIAL REGISTRATION: Clinical trial registration information for the parent
      clinical trial: Karolinska Clinical Trial Registration (2008) Unique identifier:
      CT20080014. Registered 04th January 2008.

PMID- 28750638
TI  - Erratum to: prevalence of anelloviruses (TTV, TTMDV, and TTMV) in healthy blood
      donors and in patients infected with HBV or HCV in Qatar.

PMID- 28750639
TI  - Epithelial requirement for in vitro proliferation and xenograft growth and
      metastasis of MDA-MB-468 human breast cancer cells: oncogenic rather than tumor
      suppressive role of E-cadherin.
AB  - BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is associated with
      downregulated E-cadherin and frequently with decreased proliferation.
      Proliferation may be restored in secondary metastases by mesenchymal-to
      epithelial transition (MET). We tested whether E-cadherin maintains epithelial
      proliferation in MDA-MB-468 breast cancer cells, facilitating metastatic
      colonization in severe combined immunodeficiency (SCID) mice. METHODS: EMT/MET
      markers were assessed in xenograft tumors by immunohistochemistry. Stable E
      cadherin manipulation was effected by transfection and verified by Western
      blotting, immunocytochemistry, and quantitative polymerase chain reaction (qPCR).
      Effects of E-cadherin manipulation on proliferation and chemomigration were
      assessed in vitro by performing sulforhodamine B assays and Transwell assays,
      respectively. Invasion was assessed by Matrigel outgrowth; growth in vivo was
      assessed in SCID mice; and EMT status was assessed by qPCR. Hypoxic response of E
      cadherin knockdown cell lines was assessed by qPCR after hypoxic culture.
      Repeated measures analysis of variance (ANOVA), one- and two-way ANOVA with
      posttests, and paired Student's t tests were performed to determine significance
      (p < 0.05). RESULTS: EMT occurred at the necrotic interface of MDA-MB-468
      xenografts in regions of hypoxia. Extratumoral deposits (vascular and lymphatic
      inclusions, local and axillary nodes, and lung metastases) strongly expressed E
      cadherin. MDA-MB-468 cells overexpressing E-cadherin were more proliferative and
      less migratory in vitro, whereas E-cadherin knockdown (short hairpin CDH1
      [shCDH1]) cells were more migratory and invasive, less proliferative, and took
      longer to form tumors. shCDH1-MDA-MB-468 xenografts did not contain the hypoxia
      induced necrotic areas observed in wild-type (WT) and shSCR-MDA-MB-468 tumors,
      but they did not exhibit an impaired hypoxic response in vitro. Although vimentin
      expression was not stimulated by E-cadherin knockdown in 2D or 3D cultures,
      xenografts of these cells were globally vimentin-positive rather than exhibiting
      regional EMT, and they expressed higher SNA1 than their in vitro counterparts. E
      cadherin suppression caused a trend toward reduced lung metastasis, whereas E
      cadherin overexpression resulted in the reverse trend, consistent with the
      increased proliferation rate and predominantly epithelial phenotype of MDA-MB-468
      cells outside the primary xenograft. This was also originally observed in WT
      xenografts. Furthermore, we found that patients with breast cancer that expressed
      E-cadherin were more likely to have metastases. CONCLUSIONS: E-cadherin
      expression promotes growth of primary breast tumors and conceivably the formation
      of metastases, supporting a role for MET in metastasis. E-cadherin needs to be
      reevaluated as a tumor suppressor.

PMID- 28750640
TI  - Impact of somatic PI3K pathway and ERBB family mutations on pathological complete
      response (pCR) in HER2-positive breast cancer patients who received neoadjuvant
      HER2-targeted therapies.
AB  - BACKGROUND: The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor
      tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3)
      and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family
      mutations) occur alone or co-occur with somatic mutations in the gene encoding
      the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) in 19% of
      human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Because
      ERBB family mutations can activate the PI3K/AKT pathway and likely have similar
      canonical signalling effects to PI3K pathway mutations, we investigated their
      combined impact on response to neoadjuvant HER2-targeted therapies. METHODS:
      Baseline tumour biopsies were available from 74 patients with HER2-positive
      breast cancer who were enrolled in the phase II TCHL neoadjuvant study (ICORG 10
      05) assessing TCH (docetaxel, carboplatin, trastuzumab) (n = 38) versus TCL
      (docetaxel, carboplatin, lapatinib) (n = 10) versus TCHL (docetaxel, carboplatin,
      trastuzumab, lapatinib) (n = 40), each for six cycles. Activating mutations in
      PIK3CA and ERBB family genes were identified using mass spectrometry-based
      genotyping. Phosphatase and tensin homolog (PTEN) expression was assessed by
      immunohistochemistry. RESULTS: PIK3CA and/or ERBB family mutations were detected
      in 23 (31.1%) tumour samples tested, whereas PTEN expression was low in 31.1% of
      cases tested. Mutation frequency was similar in each treatment arm (31.3% in TCH
      arm, 30% in TCL arm and 31.3% in TCHL arm) and was not influenced by oestrogen
      receptor (ER) status (27.6% in ER-negative patients, 33.3% in ER-positive
      patients) or progesterone receptor (PR) status (32.6% in PR-negative patients,
      29% in PR-positive patients). There was no significant difference in pathological
      complete response (pCR) rates between 47 patients with wild-type (WT) tumours and
      22 patients whose tumours carried mutations (in either PIK3CA or ERBB family
      genes) (42.5% vs. 54.5%; p = 0.439). Similarly, there was no significant
      difference in pCR rates between patients with PIK3CA/ERBB family mutated/PTEN-low
      (i.e., PI3K-activated) tumours and patients without PI3K activation (50% vs. 44%;
      p = 0.769). However, in the TCHL (but not the TCH) group, the pCR rate was higher
      for 9 patients with PIK3CA/ERBB family mutated tumours than for 20 patients with
      PIK3CA/ERBB family WT tumours (77.8% vs. 35%; p = 0.05). CONCLUSIONS: Our results
      indicate that patients who receive neoadjuvant TCHL and have PIK3CA/ERBB family
      mutated tumours may be more likely to have a pCR than patients with WT tumours.
      TRIAL REGISTRATION: ClinicalTrials.gov, NCT01485926 . Registered on 2 December
      2011.

PMID- 28750641
TI  - Metabolome alterations in severe critical illness and vitamin D status.
AB  - BACKGROUND: Metabolic homeostasis is substantially disrupted in critical illness.
      Given the pleiotropic effects of vitamin D, we hypothesized that metabolic
      profiles differ between critically ill patients relative to their vitamin D
      status. METHODS: We performed a metabolomics study on biorepository samples
      collected from a single academic medical center on 65 adults with systemic
      inflammatory response syndrome or sepsis treated in a 20-bed medical ICU between
      2008 and 2010. To identify key metabolites and metabolic pathways related to
      vitamin D status in critical illness, we first generated metabolomic data using
      gas and liquid chromatography mass spectroscopy. We followed this by partial
      least squares-discriminant analysis to identify individual metabolites that were
      significant. We then interrogated the entire metabolomics profile using
      metabolite set enrichment analysis to identify groups of metabolites and pathways
      that were differentiates of vitamin D status. Finally we performed logistic
      regression to construct a network model of chemical-protein target interactions
      important in vitamin D status. RESULTS: Metabolomic profiles significantly
      differed in critically ill patients with 25(OH)D <= 15 ng/ml relative to those
      with levels >15 ng/ml. In particular, increased 1,5-anhydroglucitol, tryptophan
      betaine, and 3-hydroxyoctanoate as well as decreased 2-arachidonoyl
      glycerophosphocholine and N-6-trimethyllysine were strong predictors of 25(OH)D
      >15 ng/ml. The combination of these five metabolites led to an area under the
      curve for discrimination for 25(OH)D > 15 ng/ml of 0.82 (95% CI 0.71-0.93). The
      metabolite pathways related to glutathione metabolism and glutamate metabolism
      are significantly enriched with regard to vitamin D status. CONCLUSION: Vitamin D
      status is associated with differential metabolic profiles during critical
      illness. Glutathione and glutamate pathway metabolism, which play principal roles
      in redox regulation and immunomodulation, respectively, were significantly
      altered with vitamin D status.

PMID- 28750642
TI  - CMR fluoroscopy right heart catheterization for cardiac output and pulmonary
      vascular resistance: results in 102 patients.
AB  - BACKGROUND: Quantification of cardiac output and pulmonary vascular resistance
      (PVR) are critical components of invasive hemodynamic assessment, and can be
      measured concurrently with pressures using phase contrast CMR flow during real
      time CMR guided cardiac catheterization. METHODS: One hundred two consecutive
      patients underwent CMR fluoroscopy guided right heart catheterization (RHC) with
      simultaneous measurement of pressure, cardiac output and pulmonary vascular
      resistance using CMR flow and the Fick principle for comparison. Procedural
      success, catheterization time and adverse events were prospectively collected.
      RESULTS: RHC was successfully completed in 97/102 (95.1%) patients without
      complication. Catheterization time was 20 +/- 11 min. In patients with and
      without pulmonary hypertension, baseline mean pulmonary artery pressure was 39 +/
      12 mmHg vs. 18 +/- 4 mmHg (p < 0.001), right ventricular (RV) end diastolic
      volume was 104 +/- 64 vs. 74 +/- 24 (p = 0.02), and RV end-systolic volume was 49
      +/- 30 vs. 31 +/- 13 (p = 0.004) respectively. 103 paired cardiac output and 99
      paired PVR calculations across multiple conditions were analyzed. At baseline,
      the bias between cardiac output by CMR and Fick was 5.9% with limits of agreement
      -38.3% and 50.2% with r = 0.81 (p < 0.001). The bias between PVR by CMR and Fick
      was -0.02 WU.m2 with limits of agreement -2.6 and 2.5 WU.m2 with r = 0.98 (p <
      0.001). Correlation coefficients were lower and limits of agreement wider during
      physiological provocation with inhaled 100% oxygen and 40 ppm nitric oxide.
      CONCLUSIONS: CMR fluoroscopy guided cardiac catheterization is safe, with
      acceptable procedure times and high procedural success rate. Cardiac output and
      PVR measurements using CMR flow correlated well with the Fick at baseline and are
      likely more accurate during physiological provocation with supplemental high
      concentration inhaled oxygen. TRIAL REGISTRATION: Clinicaltrials.gov NCT01287026
      , registered January 25, 2011.

PMID- 28750643
TI  - Isolated hypercholesterolemia leads to steatosis in the liver without affecting
      the pancreas.
AB  - BACKGROUND: Lipid accumulation in the liver and pancreas is primarily caused by
      combined hyperlipidemia. However, the effect of isolated hypercholesterolemia
      without hypertriglyceridemia is not fully described. Therefore, our aim was to
      investigate whether hypercholesterolemia alone leads to alterations both in
      hepatic and pancreatic lipid panel and histology in rats. METHODS: Male Wistar
      rats were fed with 2% cholesterol +0.25% cholate-supplemented diet or standard
      chow for 12 weeks. Blood was collected at weeks 0, 4, 8 and 12 to measure serum
      cholesterol and triglyceride levels. At week 12, both the pancreas and the liver
      were isolated for further histological and biochemical analysis. Hepatic and
      plasma fatty acid composition was assessed by gas chromatography. Expression of
      mRNA of major enzymes involved in saturated/unsaturated fatty acid synthesis was
      analyzed by qPCR. In separate experiments serum enzyme activities and insulin
      levels were measured at week 9. RESULTS: At week 12, rats fed with 2% cholesterol
      +0.25% cholate-supplemented diet were characterized by elevated serum cholesterol
      (4.09 +/- 0.20 vs. 2.89 +/- 0.22 mmol/L, *p < 0.05) while triglyceride (2.27 +/-
      0.05 vs. 2.03 +/- 0.03 mmol/L) and glucose levels (5.32 +/- 0.14 vs. 5.23 +/-
      0.10 mmol/L) remained unchanged. Isolated hypercholesterolemia increased hepatic
      lipid accumulation, hepatic cholesterol (5.86 +/- 0.22 vs. 1.60 +/- 0.15 ng/g
      tissue, *p < 0.05) and triglyceride contents (19.28 +/- 1.42 vs. 6.78 +/- 0.71
      ng/g tissue, *p < 0.05), and hepatic nitrotyrosine level (4.07 +/- 0.52 vs. 2.59
      +/- 0.31 ng/mg protein, *p < 0.05). The histology and tissue lipid content of the
      pancreas was not affected. Serum total protein level, alanine aminotransferase
      (ALT) and aspartate aminotransferase (AST) activities remained unchanged in
      response to isolated hypercholesterolemia while serum alkaline phosphatase
      activity (ALP) significantly increased. Plasma insulin levels did not change in
      response to isolated hypercholesterolemia suggesting an intact endocrine function
      of the pancreas. Isolated hypercholesterolemia caused a significantly increased
      hepatic and serum fatty acid level associated with a marked alteration of fatty
      acid composition. Hepatic expression of Delta9-desaturase (SCD1) was increased
      4.92*, while expression of Delta5-desaturase and Delta6-desaturase were decreased
      (0.447* and 0.577*, respectively) due to isolated hypercholesterolemia.
      CONCLUSIONS: Isolated hypercholesterolemia leads to hepatic steatosis and marked
      alterations in the hepatic lipid profile without affecting the pancreas. Altered
      fatty acid profile might mediate harmful effects of cholesterol in the liver.

PMID- 28750644
TI  - A retrospective study of reproductive outcomes after fertility-sparing surgery
      and postoperative adjuvant chemotherapy in malignant ovarian germ cell tumors and
      sex cord-stromal tumors.
AB  - BACKGROUND: To retrospectively investigate reproductive outcomes after fertility
      sparing surgery and postoperative adjuvant chemotherapy in malignant ovarian germ
      cell tumors (MOGCT) and sex cord-stromal tumors (SCST). METHODS: Data from 32
      MOGCT (6 dysgerminomas, 6 yolk sac tumors, 17 immature teratomas, and 3 mixed
      germ cell tumors) and 9 SCST (4 granulosa cell tumors and 5 sertoli-leydig cell
      tumors) aged from 18 to 35, treated in the Obstetrics and Gynecology Hospital of
      Fudan University from October 2003 to October 2013 were collected and analyzed.
      RESULTS: Average follow up was (86.3 +/- 34.4) months. Average diagnosed age was
      (25.3 +/- 3.5) years. Average chemotherapy course was (4.4 +/- 1.3) times.
      Patients are all living. Thirty one patients (75.6%) reported normal menstrual
      cycles. Twelve patients (29.3%) wished to conceive, 10 (83.3%) naturally
      conceived and 8 (66.7%) had lived birth. CONCLUSIONS: Reproductive outcomes after
      fertility-sparing surgery and postoperative adjuvant chemotherapy in MOGCT and
      SCST are favorable, meanwhile education and consultation is needed.

PMID- 28750645
TI  - Comparative effects of microvascular and macrovascular disease on the risk of
      major outcomes in patients with type 2 diabetes.
AB  - BACKGROUND: Microvascular disease is associated with a high risk of macrovascular
      events in patients with type 2 diabetes, but the impact of macrovascular disease
      on the risk of microvascular events remains unknown. We sought to evaluate the
      respective effects of prior microvascular and macrovascular disease on the risk
      of major outcomes, including microvascular events, in these patients. METHODS:
      Participants in the Action in Diabetes and Vascular Disease: PreterAx and
      DiamicroN Modified-Release Controlled Evaluation (ADVANCE) trial (n = 11,140) and
      the ADVANCE-ON post-trial study (n = 8494) were categorized into 4 groups at
      baseline: dual absence of microvascular or macrovascular disease (n = 6789),
      presence of microvascular disease alone (n = 761), macrovascular disease alone (n
      = 3196), and both (n = 394). Outcomes were all-cause mortality, major
      macrovascular events (MACE), and major clinical microvascular events. RESULTS:
      All-cause mortality, MACE, and major clinical microvascular events occurred in
      2265 (20%), 2166 (19%), and 807 (7%) participants respectively, during a median
      follow-up of 9.9 (inter-quartile interval 5.6-10.9) years. The adjusted hazard
      ratios [95% CI] of death, MACE, and major clinical microvascular events were each
      greater in patients with baseline microvascular disease (1.43 [1.20-1.71], 1.64
      [1.37-1.97], and 4.74 [3.86-5.82], respectively), macrovascular disease (1.43
      [1.30-1.57], 2.04 [1.86-2.25], and 1.26 [1.06-1.51]) or both (2.01 [1.65-2.45],
      2.92 [2.40-3.55], and 6.30 [4.93-8.06]) compared with those without these
      conditions. No interaction was observed between baseline microvascular and
      macrovascular disease for these events. The addition of microvascular disease
      (change in c-statistic [95% CI] 0.005 [0.002-0.008], p = 0.02) or macrovascular
      disease (0.005 [0.002-0.007], p < 0.0001) considered separately or together
      (0.011 [0.007-0.014], p < 0.0001) improved the discrimination and the
      classification (integrated discrimination improvement (IDI): 0.013 [0.010-0.016],
      p < 0.001; net reclassification improvement (NRI): 0.021 [0.011-0.032], p <
      0.001) of the risk of all-cause mortality. Microvascular disease improved
      discrimination (0.009 [0.003-0.014]) and classification (IDI: 0.008 [0.006
      0.010]; NRI: 0.011 [0.001-0.020]) of MACE. Baseline macrovascular disease
      modestly enhanced IDI (0.002 [0.001-0.002]) and NRI (0.041 [0.002-0.087]), but
      not discrimination, of major clinical microvascular events. CONCLUSIONS:
      Microvascular and macrovascular disease are independently associated with the 10
      year risk of death, MACE, and major clinical microvascular events in patients
      with type 2 diabetes. The coexistence of these conditions was associated with the
      highest risks.

PMID- 28750646
TI  - Metabolomics of Rhabdomyosarcoma Cell During Echovirus 30 Infection.
AB  - BACKGROUND: Echovirus 30 (E30) causes acute aseptic meningitis. Viral replication
      requires energy and macromolecular precursors derived from the metabolic network
      of the host cell. The effect of viral infection within a host cell metabolic
      activity remains unclear. METHODS: To gain an insight into cell-virus interaction
      during E30 infection we used a human rhabdomyosarcoma cell line. In a new
      approach to metabolomics, 1H NMR was used to measure the level of various
      cellular metabolites at different times of infection and morphological
      examination of the cells. Statistical analysis was done by using Confidence
      interval (CI) 95% and One-way ANOVA test. RESULTS: The1H NMR metabolite spectrum
      signals were observed between mock infected and virus infected cells. Both mock
      infected and virus infected cells utilized glucose through metabolic pathways and
      released metabolic end products. Upon infection, the concentration of Alanine,
      Lactate, Acetate, Glutamate, Tyrosine, Histidine, Phenylalanine, Creatine,
      Choline and Formate, increased. Interestingly, all of these augmented metabolites
      were decreased during later stage of infection. The cells showed wide-ranging
      lipid signals at the end of infection, which correlates with the morphological
      changes as apoptosis (programmed cell death) of cells was observed. A significant
      association was found between time interval (12 h, 24 h, and 48 h) and
      metabolites likewise Alanin, Lactate, Acetate, Glutamate, Tyrosine, Histidine,
      Phenylalanine, Creatine, Choline and Formate respectively released by cell during
      infection, which is highly significant (p < 0.01). CONCLUSION: Progressive
      breakdown and utilization of all cellular components were observed as the
      infection increased. This study is useful for monitoring the cellular metabolic
      changes during viral infection.

PMID- 28750647
TI  - High level of HIV-1 drug resistance mutations in patients with unsuppressed viral
      loads in rural northern South Africa.
AB  - BACKGROUND: Combination antiretroviral therapy (cART) has significantly reduced
      HIV morbidity and mortality in both developed and developing countries. However,
      the sustainability of cART may be compromised by the emergence of viral drug
      resistance mutations (DRM) and the cellular persistence of proviruses carrying
      these DRM. This is potentially a more serious problem in resource limited
      settings. METHODS: DRM were evaluated in individuals with unsuppressed viral
      loads after first or multiple lines of cART at two sites in rural Limpopo, South
      Africa. Seventy-two patients with viral loads of >1000 copies/ml were recruited
      between March 2014 and December 2015. Complete protease (PR) and partial Reverse
      Transcriptase (RT) sequences were amplified from both plasma RNA and paired
      proviral DNA from 35 of these subjects. Amplicons were directly sequenced to
      determine subtype and DRM using the Stanford HIV Drug Resistance Interpretation
      algorithm. RESULTS: Among the 72 samples, 69 could be PCR amplified from RNA and
      35 from both RNA and DNA. Sixty-five (94.2%) viruses were subtype C, while one
      was subtype B (1.4%), one recombinant K/C, one recombinant C/B and one
      unclassified. Fifty-eight (84%) sequences carried at least one DRM, while 11
      (15.9%) displayed no DRM. DRM prevalence according to drug class was: NRTI 60.8%
      NNRTI 65.2%, and PI 5.8%. The most common DRMs were; M184V (51.7%), K103N (50%),
      V106M (20.6%), D67N (13.3%), K65R (12%). The frequency of the DRM tracked well
      with the frequency of use of medications to which the mutations were predicted to
      confer resistance. Interestingly, a significant number of subjects showed
      predicted resistance to the newer NNRTIs, etravirine (33%) and rilpivirine (42%),
      both of which are not yet available in this setting. The proportion of DRM in RNA
      and DNA were mostly similar with the exception of the thymidine analogue
      mutations (TAMs) D67N, K70R, K219QE; and K103N which were slightly more prevalent
      in DNA than RNA. Subjects who had received cART for at least 5 years were more
      likely to harbour >2 DRM (p < 0.05) compared to those treated for a shorter
      period. DRM were more prevalent in this rural setting compared to a neighbouring
      urban setting. CONCLUSION: We found a very high prevalence of NRTI and NNRTI DRM
      in patients from rural Limpopo settings with different durations of treatment.
      The prevalence was significantly higher than those reported in urban settings in
      South Africa. The dominance of NNRTI based mutations late in treatment supports
      the use of PI based regimens for second line treatment in this setting. The
      slight dominance of TAMs in DNA from infected PBMCs compared to plasma virus
      requires further studies that should include cART subjects with suppressed virus.
      Such studies will improve our understanding of the pattern of drug resistance and
      dynamics of viral persistence in these rural settings.

PMID- 28750648
TI  - Towards a more molecular taxonomy of disease.
AB  - BACKGROUND: Disease taxonomies have been designed for many applications, but they
      tend not to fully incorporate the growing amount of molecular-level knowledge of
      disease processes, inhibiting research efforts. Understanding the degree to which
      we can infer disease relationships from molecular data alone may yield insights
      into how to ultimately construct more modern taxonomies that integrate both
      physiological and molecular information. RESULTS: We introduce a new technique we
      call Parent Promotion to infer hierarchical relationships between disease terms
      using disease-gene data. We compare this technique with both an established
      ontology inference method (CliXO) and a minimum weight spanning tree approach.
      Because there is no gold standard molecular disease taxonomy available, we
      compare our inferred hierarchies to both the Medical Subject Headings (MeSH)
      category C forest of diseases and to subnetworks of the Disease Ontology (DO).
      This comparison provides insights about the inference algorithms, choices of
      evaluation metrics, and the existing molecular content of various subnetworks of
      MeSH and the DO. Our results suggest that the Parent Promotion method performs
      well in most cases. Performance across MeSH trees is also correlated between
      inference methods. Specifically, inferred relationships are more consistent with
      those in smaller MeSH disease trees than larger ones, but there are some notable
      exceptions that may correlate with higher molecular content in MeSH. CONCLUSIONS:
      Our experiments provide insights about learning relationships between diseases
      from disease genes alone. Future work should explore the prospect of disease term
      discovery from molecular data and how best to integrate molecular data with
      anatomical and clinical knowledge. This study nonetheless suggests that disease
      gene information has the potential to form an important part of the foundation
      for future representations of the disease landscape.

PMID- 28750649
TI  - Pharmacology education and antibiotic self-medication among medical students: a
      cross-sectional study.
AB  - OBJECTIVE: Pharmacology teaches rational prescribing. Self-medication among
      medical students is recognised as a threat to rational prescribing. Antibiotic
      self-medication could cause antibiotic resistance among medical students. We
      aimed to find an association between pharmacology education and antibiotic self
      medication. RESULTS: Overall, 39% [(110/285) 95% CI 32.9-44.3] of students were
      found to have antibiotic self-medication. The percentage for antibiotic self
      medication progressively increased with the year of study. The percentage of
      antibiotic self-medication was significantly high in the "Formal Pharmacology
      Education" group (47%-77/165) in comparison to the "No Formal Pharmacology
      Education" group (28%-33/120) (P = 0.001032). Overall, the most common self
      prescribed antibiotic was amoxicillin (56%-62/110).

PMID- 28750650
TI  - Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing
      spondylitis.
AB  - BACKGROUND: The assessment and characterization of the gut microbiome has become
      a focus of research in the area of human autoimmune diseases. Ankylosing
      spondylitis is an inflammatory autoimmune disease and evidence showed that
      ankylosing spondylitis may be a microbiome-driven disease. RESULTS: To
      investigate the relationship between the gut microbiome and ankylosing
      spondylitis, a quantitative metagenomics study based on deep shotgun sequencing
      was performed, using gut microbial DNA from 211 Chinese individuals. A total of
      23,709 genes and 12 metagenomic species were shown to be differentially abundant
      between ankylosing spondylitis patients and healthy controls. Patients were
      characterized by a form of gut microbial dysbiosis that is more prominent than
      previously reported cases with inflammatory bowel disease. Specifically, the
      ankylosing spondylitis patients demonstrated increases in the abundance of
      Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561 and
      decreases in Bacteroides spp. It is noteworthy that the Bifidobacterium genus,
      which is commonly used in probiotics, accumulated in the ankylosing spondylitis
      patients. Diagnostic algorithms were established using a subset of these gut
      microbial biomarkers. CONCLUSIONS: Alterations of the gut microbiome are
      associated with development of ankylosing spondylitis. Our data suggest
      biomarkers identified in this study might participate in the pathogenesis or
      development process of ankylosing spondylitis, providing new leads for the
      development of new diagnostic tools and potential treatments.

PMID- 28750651
TI  - A cross-sectional survey of Aedes aegypti immature abundance in urban and rural
      household containers in central Colombia.
AB  - BACKGROUND: Aedes aegypti, the major vector of dengue, breeds in domestic water
      containers. The development of immature mosquitoes in such containers is
      influenced by various environmental, ecological and socioeconomic factors. Urban
      and rural disparities in water storage practices and water source supply may
      affect mosquito immature abundance and, potentially, dengue risk. We evaluated
      the effect of water and container characteristics on A. aegypti immature
      abundance in urban and rural areas. Data were collected in the wet season of 2011
      in central Colombia from 36 urban and 35 rural containers, which were either
      mosquito-positive or negative. Immature mosquitoes were identified to species.
      Data on water and container characteristics were collected from all containers.
      RESULTS: A total of 1452 Aedes pupae and larvae were collected of which 81% were
      A. aegypti and 19% A. fluviatilis. Aedes aegypti immatures were found in both
      urban and rural sites. However, the mean number of A. aegypti pupae was five
      times higher in containers in the urban sites compared to those in the rural
      sites. One of the important factors associated with A. aegypti infestation was
      frequency of container washing. Monthly-washed or never-washed containers were
      both about four times more likely to be infested than those washed every week.
      There were no significant differences between urban and rural sites in frequency
      of washing containers. Aedes aegypti immature infestation was positively
      associated with total dissolved solids, but negatively associated with dissolved
      oxygen. Water temperature, total dissolved solids, ammonia, nitrate, and organic
      matter were significantly higher in urban than in rural containers, which might
      explain urban-rural differences in breeding of A. aegypti. However, many of these
      factors vary substantially between studies and in their degree of association
      with vector breeding, therefore they may not be reliable indices for vector
      control interventions. CONCLUSIONS: Although containers in urban areas were more
      likely to be infested with A. aegypti, rural containers still provide suitable
      habitats for A. aegypti. Containers that are washed more frequent are less likely
      to produce A. aegypti. These results highlight the importance of container
      washing as an effective vector control tool in both urban and rural areas. In
      addition, alternative designs of the highly productive washbasins should continue
      to be explored. To control diseases such as dengue, Zika and chikungunya,
      effective vector breeding site control must be implemented in addition to other
      interventions.

PMID- 28750652
TI  - Awareness, attitudes, need and demand on replacement of missing teeth among a
      group of partially dentate patients attending a University Dental Hospital.
AB  - OBJECTIVE: Our objective was to assess awareness, attitudes, need and demand on
      replacement of missing teeth according to edentulous space, age, gender,
      ethnicity, educational level and socio-economical status of the patient. RESULTS:
      76.2% of the study group was opined that the missing teeth should be replaced by
      prosthetic means. Majority were keen in getting them replaced mainly for the
      comfort in mastication. Although 77.9 and 32.9% were aware of the removable
      prostheses and implants respectively, only 25.2% knew about tooth supported
      bridges as an option of replacement of missing teeth. Participants' awareness on
      tooth and implant supported prostheses is at a higher level. Participants'
      opinion on need of regular dental visit was statistically significant when
      gender, ethnicity and education level were considered. The highest demand for
      replacement of missing teeth was observed in Kennedy class I and II situations in
      both upper and lower arches. Demand for fixed prostheses was significantly
      highest in Kennedy class II in upper and lower arches. In conclusion, although
      removable prosthodontic options are known to most of the patients, their
      awareness on tooth and implant supported prostheses is also at a higher level.
      The highest demand for replacement of missing teeth is by patients with Kennedy
      class I and II situations whereas Kennedy class II being the category with
      highest demand for fixed prostheses. We recommend that the location of missing
      teeth to be considered as a priority when educating patients on the most
      appropriate prosthetic treatment options. Dentists' involvement in educating
      patients on prosthetic options needs to be improved.

PMID- 28750653
TI  - Bacteraemic urinary tract infections in a tertiary hospital in Japan: the
      epidemiology of community-acquired infections and the role of non-carbapenem
      therapy.
AB  - OBJECTIVES: This study aimed to describe the epidemiology of bacteraemic urinary
      tract infections (UTIs), especially those that were community-acquired (i.e.,
      with no discernible healthcare-associated exposure) and caused by extended
      spectrum beta-lactamase-producing Enterobacteriaceae (ESBLPE). We also evaluated
      and compared empirical antimicrobial treatments [carbapenem (CBP) vs. non
      carbapenem beta-lactam (non-CBPBL)] for bacteraemic UTIs. Finally, we reviewed
      the published literature on the effectiveness of non-CBP compared to CBP
      treatments for UTIs caused by extended-spectrum beta-lactamase-producing
      organisms. RESULTS: A total of 339 bacteraemic UTI episodes were identified; 32
      (9.4%) were caused by ESBLPE. In bacteraemic UTI episodes, ESBLPE accounted for
      8.3% of hospital-acquired cases, 10.0% of community-acquired cases, and 8.2% of
      non-healthcare-associated cases. As effective empirical therapy for ESBLPE, 12
      patients received CBP and 7 patients received non-CBPBL treatments
      [piperacillin/tazobactam (PT) or cefmetazole (CMZ)]. Age, sex, Pitt bacteraemia
      score, immunosuppressive status, and causative bacterial species were similar
      between groups; neither group experienced mortality within 14 days. The number of
      days to defervescence was similar between groups. No difference was noted in the
      rates of microbiological cure (58% vs. 57%, P = 1.0). Five of seven patients in
      the non-CBPBL group did not receive CBP during the treatment period, even as
      definitive therapy, but all experienced clinical cure.

PMID- 28750654
TI  - Different therapeutic effects of cells derived from human amniotic membrane on
      premature ovarian aging depend on distinct cellular biological characteristics.
AB  - BACKGROUND: Many reports have shown that various kinds of stem cells have the
      ability to recover premature ovarian aging (POA) function. Transplantation of
      human amniotic epithelial cells (hAECs) improves ovarian function damaged by
      chemotherapy in a mice model. Understanding of how to evaluate the distinct
      effects of adult stem cells in curing POA and how to choose stem cells in
      clinical application is lacking. METHODS: To build a different degrees of POA
      model, mice were administered different doses of cyclophosphamide: light dose (70
      mg/kg, 2 weeks), medium dose (70 mg/kg, 1 week; 120 mg/kg, 1 week), and high dose
      (120 mg/kg, 2 weeks). Enzyme-linked immunosorbent assay detected serum levels of
      sex hormones, and hematoxylin and eosin staining allowed follicle counting and
      showed the ovarian tissue structure. DiIC18(5)-DS was employed to label human
      amniotic mesenchymal stem cells (hAMSCs) and hAECs for detecting the cellular
      retention time in ovaries by a live imaging system. Proliferation of human
      ovarian granule cells (ki67, AMH, FSHR, FOXL2, and CYP19A1) and immunological
      rejection of human peripheral blood mononuclear cells (CD4, CD11b, CD19, and
      CD56) were measured by flow cytometry (fluorescence-activated cell sorting
      (FACS)). Distinction of cellular biological characteristics between hAECs and
      hAMSCs was evaluated, such as collagen secretory level (collagen I, II, III, IV,
      and VI), telomerase activity, pluripotent markers tested by western blot,
      expression level of immune molecules (HLA-ABC and HLA-DR) analyzed by FACS, and
      cytokines (growth factors, chemotactic factors, apoptosis factors, and
      inflammatory factors) measured by a protein antibody array methodology. RESULTS:
      After hAMSCs and hAECs were transplanted into a different degrees of POA model,
      hAMSCs exerted better therapeutic activity on mouse ovarian function in the high
      dose administration group, promoting the proliferation rate of ovarian granular
      cells from premature ovarian failure patients, but also provoking immune
      rejection. Meanwhile, our results showed that the biological characteristics of
      hAMSCs were superior to hAECs, but not to expression of immune molecules.
      CONCLUSIONS: These results suggest that hAMSCs are a more effective cell type to
      improve ovarian function than hAECs. Meanwhile, this distinct effect is
      attributable to cellular biological characteristics of hAMSCs (telomerase
      activity, expression level of pluripotent markers, cytokine and collagen
      secretion) that are superior to hAECs, except for immunological rejection.
      Sufficient consideration of cell properties is warranted to move forward to more
      effective clinical therapy.

PMID- 28750655
TI  - Non-genomic transmission of longevity between generations: potential mechanisms
      and evidence across species.
AB  - Accumulating animal and human data indicate that environmental exposures
      experienced during sensitive developmental periods may strongly influence risk of
      adult disease. Moreover, the effects triggered by developmental environmental
      cues can be transgenerationally transmitted, potentially affecting offspring
      health outcomes. Increasing evidence suggests a central role of epigenetic
      mechanisms (heritable alterations in gene expression occurring without changes in
      underlying DNA sequence) in mediating these effects. This review summarizes the
      findings from animal models, including worms, insects, and rodents, and also from
      human studies, indicating that lifespan and longevity-associated characteristics
      can be transmitted across generations via non-genetic factors.

PMID- 28750656
TI  - Oligomeric amyloid-beta induces MAPK-mediated activation of brain cytosolic and
      calcium-independent phospholipase A2 in a spatial-specific manner.
AB  - Alzheimer's disease (AD) is histopathologically characterized by the build-up of
      fibrillar amyloid beta (Abeta) in the form of amyloid plaques and the development
      of intraneuronal neurofibrillary tangles consisting of aggregated
      hyperphosphorylated Tau. Although amyloid fibrils were originally considered
      responsible for AD pathogenesis, recent convincing evidence strongly implicates
      soluble oligomeric Abeta as the primary neurotoxic species driving disease
      progression. A third largely ignored pathological hallmark, originally described
      by Alois Alzheimer, is the presence of "adipose inclusions", suggestive of
      aberrant lipid metabolism. The molecular mechanisms underlying these "lipoid
      granules", as well as their potential link to soluble and/or fibrillar Abeta
      remain largely unknown. Seeking to better-understand these conundrums, we took
      advantage of the powerful technology of multidimensional mass spectrometry-based
      shotgun lipidomics and an AD transgenic mouse model overexpressing mutant amyloid
      precursor protein (APP E693Delta-Osaka-), where AD-like pathology and
      neurodegeneration occur as a consequence of oligomeric Abeta accumulation in the
      absence of amyloid plaques. Our results revealed for the first time that APP
      overexpression and oligomeric Abeta accumulation lead to an additive global
      accumulation of nonesterified polyunsaturated fatty acids (PUFAs) independently
      of amyloid plaques. Furthermore, we revealed that this accumulation is mediated
      by an increase in phospholipase A2 (PLA2) activity, evidenced by an accumulation
      of sn-1 lysophosphatidylcholine and by MAPK-mediated phosphorylation/activation
      of group IV Ca2+-dependent cytosolic (cPLA2) and the group VI Ca2+-independent
      PLA2 (iPLA2) independently of PKC. We further revealed that Abeta-induced
      oxidative stress also disrupts lipid metabolism via reactive oxygen species
      mediated phospholipid cleavage leading to increased sn-2 lysophosphatidylcholine
      as well as lipid peroxidation and the subsequent accumulation of 4
      hydroxynonenal. Brain histological studies implicated cPLA2 activity with
      arachidonic acid accumulation within myelin-rich regions, and iPLA2 activity with
      docosahexaenoic acid accumulation within pyramidal neuron-rich regions. Taken
      together, our results suggest that PLA2-mediated accumulation of free PUFAs
      drives AD-related disruption of brain lipid metabolism.

PMID- 28750657
TI  - Rapid expression and purification of the hepatitis delta virus antigen using the
      methylotropic yeast Pichia pastoris.
AB  - OBJECTIVE: Patients with dual hepatitis B (HBV) and hepatitis D (HDV) virus
      infection are at an increased risk of progression to liver cirrhosis and
      hepatocellular carcinoma than patients with a single viral infection. Treatment
      of viral hepatitis due to dual HBV/HDV infection represents a challenge.
      Currently there is no vaccine against HDV. Recombinant production of HDV antigen
      (HDAg) is the first step towards a potential vaccine candidate and the
      development of assays for HDV detection. RESULTS: This study demonstrates the
      expression of one HDAg isoform, S-HDAg, in Pichia pastoris. A recombinant vector
      carrying a tagged gene encoding S-HDAg under the control of the methanol
      inducible promoter AOX1 was designed and integrated into P. pastoris X33. The
      protein, which was purified using a Ni2+ affinity column and eluted at 100-150 mM
      imidazole, has potential as a recombinant antigen for further study.

PMID- 28750658
TI  - Complement regulator CD59 prevents peripheral organ injury in rats made
      seropositive for neuromyelitis optica immunoglobulin G.
AB  - Pathogenesis in aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive
      neuromyelitis optica spectrum disorders (herein called NMO) involves complement
      dependent cytotoxicity initiated by AQP4-IgG binding to astrocyte AQP4. We
      recently reported that rats lacking complement inhibitor protein CD59 were highly
      susceptible to development of NMO pathology in brain and spinal cord following
      direct AQP4-IgG administration (Yao and Verkman, Acta Neuropath Commun 2017,
      5:15). Here, we report evidence that CD59 is responsible for protection of
      peripheral, AQP4-expressing tissues in seropositive NMO. Rats made seropositive
      by intraperitoneal injection of AQP4-IgG developed marked weakness by 24 h and
      died soon thereafter. Serum creatine phosphokinase at 24 h was >900-fold greater
      in seropositive CD59-/- rats than in seropositive CD59+/+ (or control) rats. AQP4
      expressing cells in skeletal muscle and kidney, but not in stomach, of
      seropositive CD59-/- rats showed injury with deposition of AQP4-IgG and activated
      complement C5b-9, and inflammation. Organ injury in seropositive CD59-/- rats was
      prevented by a complement inhibitor. Significant pathological changes in
      seropositive CD59-/- rats were not seen in optic nerve, spinal cord or brain,
      including circumventricular tissue. These results implicate a major protective
      role of CD59 outside of the central nervous system in seropositive NMO, and hence
      offer an explanation as to why peripheral, AQP4-expressing cells are largely
      unaffected in NMO.

PMID- 28750659
TI  - Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative
      extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy
      for borderline resectable adenocarcinoma of the head of the pancreas.
AB  - BACKGROUND: Borderline resectable pancreatic cancers infiltrate into adjacent
      vascular structures to an extent that makes an R0 resection unlikely when
      pancreatectomy is performed de novo. In a pilot study, Alliance for Clinical
      Trials in Oncology Trial A021101, the median survival of patients who received
      chemotherapy and radiation prior to anticipated pancreatectomy was 22 months, and
      64% of operations achieved an R0 resection. However, the individual contributions
      of preoperative chemotherapy and radiation therapy to therapeutic outcome remain
      poorly defined. METHODS: In Alliance for Clinical Oncology Trial A021501, a
      recently activated randomized phase II trial, patients (N = 134) with a CT or MRI
      showing a biopsy-confirmed pancreatic ductal adenocarcinoma that meets centrally
      reviewed anatomic criteria for borderline resectable disease will be randomized
      to receive either 8 cycles of modified FOLFIRINOX (oxaliplatin 85 mg/m2,
      irinotecan 180 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400
      mg/m2 over 2 days for 4 cycles) or to 7 cycles of modified FOLFIRINOX followed by
      stereotactic body radiation therapy (33-40 Gy in 5 fractions). Patients without
      evidence of disease progression following preoperative therapy will undergo
      pancreatectomy and will subsequently receive 4 cycles of postoperative modified
      FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, bolus 5-fluorouracil 400
      mg/m2, and infusional 5-fluorouracil 2400 mg/m2 over 2 days for 4 cycles). The
      primary endpoint is the 18-month overall survival rate of patients enrolled into
      each of the two treatment arms. An interim analysis of the R0 resection rate
      within each arm will be conducted to assess treatment futility after accrual of
      30 patients. Secondary endpoints include rates of margin-negative resection and
      event-free survival. The primary analysis will compare the 18-month overall
      survival rate of each arm to a historical control rate of 50%. The trial is
      activated nationwide and eligible to be opened for accrual at any National
      Clinical Trials Network cooperative group member site. DISCUSSION: This study
      will help define standard preoperative treatment regimens for borderline
      resectable pancreatic cancer and position the superior arm for further evaluation
      in future phase III trials. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02839343
      , registered July 14, 2016.

PMID- 28750660
TI  - ReMixT: clone-specific genomic structure estimation in cancer.
AB  - Somatic evolution of malignant cells produces tumors composed of multiple clonal
      populations, distinguished in part by rearrangements and copy number changes
      affecting chromosomal segments. Whole genome sequencing mixes the signals of
      sampled populations, diluting the signals of clone-specific aberrations, and
      complicating estimation of clone-specific genotypes. We introduce ReMixT, a
      method to unmix tumor and contaminating normal signals and jointly predict
      mixture proportions, clone-specific segment copy number, and clone specificity of
      breakpoints. ReMixT is free, open-source software and is available at
      http://bitbucket.org/dranew/remixt .

PMID- 28750661
TI  - Human dental pulp pluripotent-like stem cells promote wound healing and muscle
      regeneration.
AB  - BACKGROUND: Dental pulp represents an easily accessible autologous source of
      adult stem cells. A subset of these cells, named dental pulp pluripotent-like
      stem cells (DPPSC), shows high plasticity and can undergo multiple population
      doublings, making DPPSC an appealing tool for tissue repair or maintenance.
      METHODS: DPPSC were harvested from the dental pulp of third molars extracted from
      young patients. Growth factors released by DPPSC were analysed using antibody
      arrays. Cells were cultured in specific differentiation media and their
      endothelial, smooth and skeletal muscle differentiation potential was evaluated.
      The therapeutic potential of DPPSC was tested in a wound healing mouse model and
      in two genetic mouse models of muscular dystrophy (Scid/mdx and Sgcb-null Rag2
      null gammac-null). RESULTS: DPPSC secreted several growth factors involved in
      angiogenesis and extracellular matrix deposition and improved vascularisation in
      all three murine models. Moreover, DPPSC stimulated re-epithelialisation and
      ameliorated collagen deposition and organisation in healing wounds. In dystrophic
      mice, DPPSC engrafted in the skeletal muscle of both dystrophic murine models and
      showed integration in muscular fibres and vessels. In addition, DPPSC treatment
      resulted in reduced fibrosis and collagen content, larger cross-sectional area of
      type II fast-glycolytic fibres and infiltration of higher numbers of
      proangiogenic CD206+ macrophages. CONCLUSIONS: Overall, DPPSC represent a
      potential source of stem cells to enhance the wound healing process and slow down
      dystrophic muscle degeneration.

PMID- 28750662
TI  - Impact of hypertension with or without diabetes on left ventricular remodeling in
      rural Chinese population: a cross-sectional study.
AB  - BACKGROUND: The aim of this study was to assess the impact of hypertension with
      or without diabetes on left ventricular (LV) remodeling in rural Chinese
      population. METHODS: A total of 10,270 participants were classified into control
      group, hypertension without diabetes (HT) group, and hypertension with diabetes
      (HT + DM) group. We compared clinical characteristics and echocardiographic
      parameters, and used multivariable logistic regression analysis to assess the
      associations of interest. RESULTS: HT + DM group had higher interventricular
      septal thickness (IVSd), posterior wall thickness (PWTd), left ventricular mass
      (LVM), LVM index (LVMI), relative wall thickness (RWT), left atrial diameter
      (LAD), A wave and lower E wave than HT group (all P < 0.05). The prevalence rates
      of left ventricular hypertrophy (LVH) and abnormal geometry were statistically
      different among three groups (P < 0.001) and eccentric hypertrophy was the
      highest proportion of geometry abnormality. Logistic regression analysis
      suggested that subjects in HT and HT + DM groups had odds ratio (OR) values of
      2.81, 4.41, 2.24 and 3.94, 7.20, 2.38 for LVH, concentric hypertrophy and
      eccentric hypertrophy in the total population, respectively, compared to control
      group. When compared with HT group, those in HT + DM group had approximately 1.40
      , 1.61- and 1.38-, 1.71-fold increased risk for LVH and concentric hypertrophy in
      the total and female population separately, but no association of HT + DM with
      LVH and abnormal geometrical patterns was found in men. CONCLUSIONS: This study
      demonstrated that, to varying degrees, hypertension was associated with LV
      remodeling in rural Chinese population, and this risk association was obviously
      increased for LVH and concentric hypertrophy when accompanied by diabetes,
      especially for women.

PMID- 28750663
TI  - Social capital and health during pregnancy; an in-depth exploration from rural
      Sri Lanka.
AB  - BACKGROUND: Dimensions of social capital relevant to health in pregnancy are
      sparsely described in the literature. This study explores dimensions of social
      capital and the mechanisms in which they could affect the health of rural Sri
      Lankan pregnant women. METHODS: An exploratory qualitative study of solicited
      diaries written by pregnant women on their social relationships, diary interviews
      and in-depth interviews with key informants was conducted. A framework approach
      for qualitative data analysis was used. RESULTS: Pregnant women (41), from eight
      different communities completed diaries and 38 post-diary interviews. Sixteen key
      informant interviews were conducted with public health midwives and senior
      community dwellers. We identified ten cognitive and five structural constructs of
      social capital relevant to health in pregnancy. Domestic and neighborhood
      cohesion were the most commonly expressed constructs. Social support was limited
      to support from close family, friends and public health midwives. A high density
      of structural social capital was observed in the micro-communities. Membership in
      local community groups was not common. Four different pathways by which social
      capital could influence health in pregnancy were identified. These include micro
      level cognitive social capital by promoting mental wellbeing; micro-level
      structural social capital by reducing minor ailments in pregnancy; micro-level
      social support mechanisms promoting physical and mental wellbeing through
      psychosocial resources and health systems at each level providing focused
      maternal care. CONCLUSION: Current tools available may not contain the relevant
      constructs to capture the unique dimensions of social capital in pregnancy.
      Social capital can influence health during pregnancy, mainly through improved
      psychosocial resources generated by social cohesion in micro-communities and by
      the embedded neighborhood public health services.

PMID- 28750664
TI  - Harvesting multipotent progenitor cells from a small sample of tonsillar biopsy
      for clinical applications.
AB  - BACKGROUND: Human adult stem cells hold the potential for the cure of numerous
      conditions and degenerative diseases. They possess major advantages over
      pluripotent stem cells as they can be derived from donors at any age, and
      therefore pose no ethical concerns or risk of teratoma tumor formation in vivo.
      Furthermore, they have a natural ability to differentiate and secrete factors
      that promote tissue healing without genetic manipulation. However, at present,
      clinical applications of adult stem cells are limited by a shortage of a
      reliable, standardized, and easily accessible tissue source which does not rely
      on specimens discarded from unrelated surgical procedures. METHOD: Human tonsil
      derived mesenchymal progenitor cells (MPCs) were isolated from a small sample of
      tonsillar tissue (average 0.88 cm3). Our novel procedure poses a minimal
      mechanical and enzymatic insult to the tissue, and therefore leads to high cell
      viability and yield. We characterized these MPCs and demonstrated robust
      multipotency in vitro. We further show that these cells can be propagated and
      maintained in xeno-free conditions. RESULTS: We have generated tonsillar biopsy
      derived MPC (T-MPC) lines from multiple donors across a spectrum of age, sex, and
      race, and successfully expanded them in culture. We characterized them by cell
      surface markers, as well as in vitro expansion and differentiation potential. Our
      procedure provides a robust yield of tonsillar biopsy-derived T-MPCs.
      CONCLUSIONS: Millions of MPCs can be harvested from a sample smaller than 1 g,
      which can be collected from a fully awake donor in an outpatient setting without
      the need for general anesthesia or hospitalization. Our study identifies
      tonsillar biopsy as an abundant source of adult MPCs for regenerative medicine.

PMID- 28750665
TI  - Renal damage induced by pemetrexed causing drug discontinuation: a case report
      and review of the literature.
AB  - BACKGROUND: Pemetrexed maintenance therapy holds tremendous potential in
      improving the survival of patients with advanced pulmonary adenocarcinoma. Major
      side effects include myelosuppression and cutaneous reactions. However, little
      data are available on pemetrexed nephrotoxicity. Our case describes clinically
      relevant renal events leading to treatment discontinuation in routine practice.
      CASE PRESENTATION: We report a case of a 69-year-old Moroccan man treated for
      metastatic non-small cell lung cancer. He was not on any other medications and he
      did not receive any nephrotoxic agents. He was exposed to intravenously
      administered contrast from thoracoabdominal computed tomography in the week of
      his last pemetrexed treatment. He developed kidney disease related to pemetrexed.
      He was submitted to renal biopsy, which showed acute tubular damage and
      interstitial fibrosis. His kidney function remained impaired, but stable, after
      discontinuation of pemetrexed therapy. He died 5 months later. CONCLUSIONS:
      Medical oncologists should be aware of renal adverse events for patients with
      advanced non-small cell lung cancer eligible for pemetrexed maintenance therapy.
      Suggestions for mitigating the risk for renal toxicities (dehydration, non
      steroidal anti-inflammatory drugs and zoledronic acid, radiocontrast agents)
      during pemetrexed maintenance should be followed to enable early detection and
      management of this adverse event.

PMID- 28750666
TI  - Perceptions of overweight by primary carers (mothers/grandmothers) of under five
      and elementary school-aged children in Bandung, Indonesia: a qualitative study.
AB  - BACKGROUND: The prevalence of childhood overweight has increased in the past two
      decades in Indonesia. Even though prevalence is escalating, there is a lack of
      qualitative evidence to assist in the design and implementation of strategies to
      tackle this issue. This study aimed to explore the view of primary carers
      (mothers and grandmothers) from different socio-economic-status groups, on
      childhood overweight in the Greater Bandung Area, Indonesia. METHODS: We
      conducted 12 focus groups discussions with a total of 94 carers of under-five and
      7-12 years children, from June to October 2016. We used the grounded theory
      approach in our analysis. RESULTS: Three main categories emerged: the concept of
      overweight, factors contributing to overweight, and awareness and feelings
      towards overweight children. Most carers from all SES groups defined overweight
      subjectively, while a few from the low SES group defined it objectively. Most
      carers from low and high SES groups agreed with the concept "chubbier is
      healthier". All carers had some knowledge of the main factors that contribute to
      childhood overweight: dietary factors, activity levels and sedentary behavior,
      and hereditary factors. Carers from all SES groups described similar
      characteristics of overweight; carers from low and intermediate SES groups had
      mixed feelings while all high SES carers have negative feelings about overweight
      children, mostly related to stigma. However, carers who identified their own
      children as being overweight expressed sensitivity about this weight status,
      especially their physical abilities. Almost all carers knew their children's
      current weight while less than two thirds knew their children's height.
      CONCLUSIONS: There are several policy implications. Firstly, health-related
      knowledge of the primary carers is of great importance and needs augmenting. To
      increase that knowledge, there is a role for front-line health practitioners
      (doctors/midwives/nurses) to be more active in educating the community. Secondly,
      simpler and more effective ways to disseminate healthy lifestyle messages to
      carers is required. Thirdly, by placing more emphasis on carers monitoring their
      children's growth may encourage carers to take steps to keep their children in
      the healthy weight and height ranges. Fourthly, the Department of Education may
      need to improve the quality and quantity of physical activity in schools.

PMID- 28750667
TI  - Co-existence of Blau syndrome and NAID? Diagnostic challenges associated with
      presence of multiple pathogenic variants in NOD2 gene: a case report.
AB  - BACKGROUND: Pediatric autoinflammatory diseases are rare and still poorly
      understood conditions resulting from defective genetic control of innate immune
      system, inter alia from anomalies of NOD2 gene. The product of this gene is Nod2
      protein, taking part in maintenance of immune homeostasis. Clinical form of
      resultant autoinflammatory condition depends on NOD2 genotype; usually patients
      with NOD2 defects present with Blau syndrome, NOD2-associated autoinflammatory
      disease (NAID) or Crohn's disease. CASE PRESENTATION: We present the case of a 7
      year-old girl with co-existing symptoms of two rare diseases, Blau syndrome and
      NAID. Overlapping manifestations of two syndromes raised a significant diagnostic
      challenge, until next-generation molecular test (NGS) identified presence of
      three pathogenic variants of NOD2 gene: P268S, IVS8+158, 1007 fs, and established
      the ultimate diagnosis. CONCLUSION: Presence of multiple genetical abnormalities
      resulted in an ambiguous clinical presentation with overlapping symptoms of Blau
      syndrome and NAID. Final diagnosis of autoinflammatory disease opened new
      therapeutic possibilities, including the use of biological treatments.

PMID- 28750668
TI  - From hybridomas to a robust microalgal-based production platform: molecular
      design of a diatom secreting monoclonal antibodies directed against the Marburg
      virus nucleoprotein.
AB  - BACKGROUND: The ideal protein expression system should provide recombinant
      proteins in high quality and quantity involving low production costs only.
      However, especially for complex therapeutic proteins like monoclonal antibodies
      many challenges remain to meet this goal and up to now production of monoclonal
      antibodies is very costly and delicate. Particularly, emerging disease outbreaks
      like Ebola virus in Western Africa in 2014-2016 make it necessary to reevaluate
      existing production platforms and develop robust and cheap alternatives that are
      easy to handle. RESULTS: In this study, we engineered the microalga Phaeodactylum
      tricornutum to produce monoclonal IgG antibodies against the nucleoprotein of
      Marburg virus, a close relative of Ebola virus causing severe hemorrhagic fever
      with high fatality rates in humans. Sequences for both chains of a mouse IgG
      antibody were retrieved from a murine hybridoma cell line and implemented in the
      microalgal system. Fully assembled antibodies were shown to be secreted by the
      alga and antibodies were proven to be functional in western blot, ELISA as well
      as IFA studies just like the original hybridoma produced IgG. Furthermore,
      synthetic variants with constant regions of a rabbit IgG and human IgG with
      optimized codon usage were produced and characterized. CONCLUSIONS: This study
      highlights the potential of microalgae as robust and low cost expression platform
      for monoclonal antibodies secreting IgG antibodies directly into the culture
      medium. Microalgae possess rapid growth rates, need basically only water, air and
      sunlight for cultivation and are very easy to handle.

PMID- 28750669
TI  - Population-level estimates of the proportion of Plasmodium vivax blood-stage
      infections attributable to relapses among febrile patients attending Adama
      Malaria Diagnostic Centre, East Shoa Zone, Oromia, Ethiopia.
AB  - BACKGROUND: Malaria is ranked as the leading communicable disease in Ethiopia,
      where Plasmodium falciparum and Plasmodium vivax are co-endemic. The incidence of
      P. vivax is usually considered to be less seasonal than P. falciparum. Clinical
      cases of symptomatic P. falciparum exhibit notable seasonal variation, driven by
      rainfall-dependent variation in the abundance of Anopheles mosquitoes. A similar
      peak of clinical cases of P. vivax is usually observed during the rainy season.
      However, the ability of P. vivax to relapse causing new blood-stage infections
      weeks to months after an infectious mosquito bite can lead to substantial
      differences in seasonal patterns of clinical cases. These cannot be detected with
      currently available diagnostic tools and are not cleared upon treatment with
      routinely administered anti-malarial drugs. METHODS: A health- facility based
      cross-sectional study was conducted in Adama malaria diagnostic centre from May
      2015 to April 2016. Finger-prick blood samples were collected for thin and thick
      blood film preparation from participants seeking treatment for suspected cases of
      febrile malaria. Informed consent was obtained from each study participant or
      their guardians. Seasonal patterns in malaria cases were analysed using
      statistical models, identifying the peaks in cases, and the seasonally varying
      proportion of P. vivax cases attributable to relapses. RESULTS: The proportion of
      patients with malaria detectable by light microscopy was 36.1% (1141/3161) of
      which P. vivax, P. falciparum, and mixed infections accounted for 71.4, 25.8 and
      2.8%, respectively. Of the febrile patients diagnosed, 2134 (67.5%) were males
      and 1919 (60.7%) were urban residents. The model identified a primary peak in P.
      falciparum and P. vivax cases from August to October, as well as a secondary peak
      of P. vivax cases from February to April attributable to cases arising from
      relapses. During the secondary peak of P. vivax cases approximately 77% (95% CrI
      68, 84%) of cases are estimated to be attributable to relapses. During the
      primary peak from August to October, approximately 40% (95% CrI 29, 57%) of cases
      are estimated to be attributable to relapses. DISCUSSION: It is not possible to
      diagnose whether a P. vivax case has been caused by blood-stage infection from a
      mosquito bite or a relapse. However, differences in seasonal patterns of P.
      falciparum and P. vivax cases can be used to estimate the population-level
      proportion of P. vivax cases attributable to relapses. These observations have
      important implications for the epidemiological assessment of vivax malaria, and
      initiating therapy that is effective against both blood stages and relapses.

PMID- 28750670
TI  - The experience of a nationwide Community of Practice to set up Regional
      Prevention Plans in Italy.
AB  - BACKGROUND: In 2010, the Italian Ministry of Health decided to start the planning
      process to elaborate the National Plan of Prevention 2010-2012 jointly with the
      21 Regions. The National Institute of Health was responsible for supporting
      regional planners (RPs) by an original participatory approach of a web-based
      Community of Practice (CoP) to set up their own Regional Plans of Prevention. In
      this paper, we summarise the theoretical framework adopted, the main phases
      characterising the lifecycle of the nationwide CoP, the evaluation approach
      adopted and its findings. METHODS: Following the CoP theoretical framework from
      Wenger, an initial group of RPs were trained on Project Cycle Management as a
      planning method and thereafter they started interacting on a web-based Moodle
      platform for 8 months. The CoP evaluation mainly took into account aspects of
      'immediate value', such as members interactions within the website, and several
      quantitative and qualitative tools were used to monitor changes over time. Data
      were retrieved from Moodle statistics or directly from the RPs by the means of a
      Knowledge, Attitude and Practice survey, a reaction survey, SWOT analysis and
      focus groups. RESULTS: The level of individual RPs knowledge increased after the
      initial course from 55.7% to 75%, attitudes and competence perception about the
      planning process method also showed an overall favourable change. During the CoP
      life span, the number of members increased from the original 98 RPs to include up
      to 600 new members on the basis of spontaneous demand. From April 2010 to January
      2011, the 'vital signs' of the CoP were monitored, including RP logins (13,450
      total logins and 3744 unique logins), views (27,522) and posts (1606) distributed
      in 326 forum discussion threads. Data and information retrieved from quantitative
      and qualitative evaluation approaches proved to be useful for the management and
      follow-up of the CoP. CONCLUSIONS: The CoP experience was successful as 19 out of
      20 Regions submitted their Regional Preventive Plan to their Ministry of Health
      within the due deadline. The CoP has proved to be an approach able to optimise
      resources and expertise, capitalising and generating new knowledge. However, more
      efforts should be deployed to define innovative ways to evaluate its values,
      tangible and intangible, as well as the return of investment.

PMID- 28750671
TI  - Adaptive lymphocyte profiles correlate to brain Abeta burden in patients with
      mild cognitive impairment.
AB  - BACKGROUND: We previously found that subjects with amnestic mild cognitive
      impairment exhibit a pro-inflammatory immune profile in the cerebrospinal fluid
      similar to multiple sclerosis, a central nervous system autoimmune disease. We
      therefore hypothesized that early neuroinflammation would reflect increases in
      brain amyloid burden during amnestic mild cognitive impairment. METHODS:
      Cerebrospinal fluid and blood samples were collected from 24 participants with
      amnestic mild cognitive impairment (12 men, 12 women; 66 +/- 6 years; 0.5
      Clinical Dementia Rating) enrolled in the AETMCI study. Analyses of cerebrospinal
      fluid and blood included immune profiling by multi-parameter flow cytometry,
      genotyping for apolipoprotein (APO)epsilon, and quantification of cytokine and
      immunoglobin levels. Amyloid (A)beta deposition was determined by 18F-florbetapir
      positron emission tomography. Spearman rank order correlations were performed to
      assess simple linear correlation for parameters including amyloid imaging,
      central and peripheral immune cell populations, and protein cytokine levels.
      RESULTS: Soluble Abeta42 in the cerebrospinal fluid declined as Abeta deposition
      increased overall and in the precuneous and posterior cingulate cortices.
      Lymphocyte profiling revealed a significant decline in T cell populations in the
      cerebrospinal fluid, specifically CD4+ T cells, as Abeta deposition in the
      posterior cingulate cortex increased. In contrast, increased Abeta burden
      correlated positively with increased memory B cells in the cerebrospinal fluid,
      which was exacerbated in APOepsilon4 carriers. For peripheral circulating
      lymphocytes, only B cell populations decreased with Abeta deposition in the
      precuneous cortex, as peripheral T cell populations did not correlate with
      changes in brain amyloid burden. CONCLUSIONS: Elevations in brain Abeta burden
      associate with a shift from T cells to memory B cells in the cerebrospinal fluid
      of subjects with amnestic mild cognitive impairment in this exploratory cohort.
      These data suggest the presence of cellular adaptive immune responses during
      Abeta accumulation, but further study needs to determine whether lymphocyte
      populations contribute to, or result from, Abeta dysregulation during memory
      decline on a larger cohort collected at multiple centers. TRIAL REGISTRATION:
      AETMCI NCT01146717.

PMID- 28750672
TI  - Frequency of Alu insertions within the ACE and PR loci in Northwestern Mexicans.
AB  - OBJECTIVE: Presently, non-LTR retrotransposons are the most active mobile
      elements in the human genome. Among these, Alu elements are highly represented in
      the modern population. Worldwide, distribution of Alu polymorphisms
      (insertion/deletion; I/D) shows variability between different populations. Two
      Alu insertion loci, ACE and PR, are significant biomarkers that have served in
      several genotype-phenotype association studies. In Mexico, studies concerning the
      frequency of these biomarkers have been conducted mainly in subpopulations from
      central and southern regions. Here, we screened a population sample of the
      northwestern region to gain further knowledge regarding the prevalence of Alu
      polymorphisms within ACE and PR loci. RESULTS: For ACE locus, the observed
      genotype frequencies were 26.5, 51.0 and 22.5% for II, ID, and DD, respectively;
      and allelic frequencies for I and D were 52 and 48%. Whereas respective genotype
      frequencies for PR locus were 2.7, 26.5 and 70.8%, and the corresponding allele
      frequencies were 16 and 84%. Furthermore, the insertion frequency within ACE
      locus was similar between central, western and northwestern subpopulations, and
      rather higher in southeastern subpopulation (p < 0.05). Although the occurrence
      of Alu polymorphisms within PR locus has not been widely examined, the insertion
      frequency was higher in northwestern subpopulation, as compared with western and
      southeastern subpopulations (p < 0.05). Based on the frequency of Alu insertions
      found in ACE and PR loci, subpopulations from the northwestern, western and
      central regions share a common genetic origin, but apparently not with the
      subpopulation from the southeastern region, in accordance with the notion that
      assumes the existence of a broad genomic diversity in the Mexican population. In
      addition, the high prevalence of Alu insertions reveals their potential
      application as biomarkers with prognostic value for the associated diseases;
      e.g., as part of the standard protocols for clinical diagnosis.

PMID- 28750673
TI  - The intervention process in the European Fans in Training (EuroFIT) trial: a
      mixed method protocol for evaluation.
AB  - BACKGROUND: EuroFIT is a gender-sensitised, health and lifestyle program
      targeting physical activity, sedentary time and dietary behaviours in men. The
      delivery of the program in football clubs, led by the clubs' community coaches,
      is designed to both attract and engage men in lifestyle change through an
      interest in football or loyalty to the club they support. The EuroFIT program
      will be evaluated in a multicentre pragmatic randomised controlled trial (RCT),
      for which ~1000 overweight men, aged 30-65 years, will be recruited in 15 top
      professional football clubs in the Netherlands, Norway, Portugal and the UK. The
      process evaluation is designed to investigate how implementation within the RCT
      is achieved in the various football clubs and countries and the processes through
      which EuroFIT affects outcomes. METHODS: This mixed methods evaluation is guided
      by the Medical Research Council (MRC) guidance for conducting process evaluations
      of complex interventions. Data will be collected in the intervention arm of the
      EuroFIT trial through: participant questionnaires (n = 500); attendance sheets
      and coach logs (n = 360); observations of sessions (n = 30); coach questionnaires
      (n = 30); usage logs from a novel device for self-monitoring physical activity
      and non-sedentary behaviour (SitFIT); an app-based game to promote social support
      for physical activity outside program sessions (MatchFIT); interviews with
      coaches (n = 15); football club representatives (n = 15); and focus groups with
      participants (n = 30). Written standard operating procedures are used to ensure
      quality and consistency in data collection and analysis across the participating
      countries. Data will be analysed thematically within datasets and overall
      synthesis of findings will address the processes through which the program is
      implemented in various countries and clubs and through which it affects outcomes,
      with careful attention to the context of the football club. DISCUSSION: The
      process evaluation will provide a comprehensive account of what was necessary to
      implement the EuroFIT program in professional football clubs within a trial
      setting and how outcomes were affected by the program. This will allow us to re
      appraise the program's conceptual base, optimise the program for post-trial
      implementation and roll out, and offer suggestions for the development and
      implementation of future initiatives to promote health and wellbeing through
      professional sports clubs. TRIAL REGISTRATION: ISRCTN81935608 . Registered on 16
      June 2015.

PMID- 28750674
TI  - Complementary feeding practices among children in Benishangul Gumuz Region,
      Ethiopia.
AB  - BACKGROUND: Appropriate complementary feeding helps to reduces child's risk of
      undernutrition, infectious disease and related mortality. However, complementary
      feeding practices are sub-optimal in Ethiopia. There is, however, also limited
      evidence in the country, particularly of Pawie District. Therefore, this study
      aimed to assess timely initiation of complementary feeding and associated factors
      among mothers who had children aged 6-23 months in Pawie District, Benishangul
      Gumuz Regional State. METHODS: A community based cross-sectional study was
      conducted in Pawie District from February 01 to March 29, 2015. A multi-stage
      sampling technique was employed to select 806 mother-child pairs. Multivariable
      logistic regression analysis was used to investigate factors associated with
      timely initiation of complementary feeding. Adjusted odds ratio (AOR) with
      corresponding 95% Confidence Interval was calculated to show the strength of
      association. A p value of <0.05 was used to declare significance of association.
      RESULTS: The overall prevalence of timely initiation of complementary feeding was
      61.8%. One quarter (23.7%) of children had good dietary diversity and 32.7% of
      children aged 12-23 months were fed with appropriate meal frequency. Mother's
      place of residence: urban settlement [AOR = 2.11, 95% CI 1.47, 3.02] and
      postnatal checkup [AOR = 1.68, 95% CI 1.15, 2.45] were significantly associated
      with timely initiation of complementary feeding. CONCLUSIONS: The prevalence of
      timely initiation of complementary feeding was low in Pawie District. Therefore,
      further strengthening maternal postnatal care utilization is a key to improve
      timely initiation of complementary feeding. Moreover, attention needs to be given
      to the rural mothers.

PMID- 28750675
TI  - Differential role of CSF fatty acid binding protein 3, alpha-synuclein, and
      Alzheimer's disease core biomarkers in Lewy body disorders and Alzheimer's
      dementia.
AB  - BACKGROUND: Neurodegenerative disorders such as Alzheimer's disease (AD),
      Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB)
      share clinical and molecular features. Cerebrospinal fluid (CSF) biomarkers may
      help the characterization of these diseases, improving the differential
      diagnosis. We evaluated the diagnostic performance of five CSF biomarkers across
      a well-characterized cohort of patients diagnosed with AD, DLB, PDD, and
      Parkinson's disease (PD). METHODS: A total of 208 patients were enrolled in 3
      European centers. The diagnostic groups (AD, n = 48; DLB, n = 40; PDD, n = 20;
      PD, n = 54) were compared with cognitively healthy neurological control subjects
      (patients with other neurological diseases [OND], n = 46). CSF levels of fatty
      acid binding protein 3, heart type (FABP3), alpha-synuclein (alpha-syn), amyloid
      beta peptide 1-42, total tau (t-tau), and phosphorylated tau 181 (p-tau) were
      assessed with immunoassays. Univariate and multivariate statistical analyses were
      applied to calculate the diagnostic value of the biomarkers as well as their
      association with clinical scores. RESULTS: FABP3 levels were significantly
      increased in patients with AD and DLB compared with those with PD and OND (p <
      0.001). CSF t-tau, p-tau, and alpha-syn were significantly higher in patients
      with AD than in patients with PDD, DLB, PD, and OND. Combination of FABP3 with p
      tau showed high accuracy for the differential diagnosis between AD and DLB (AUC
      0.92), whereas patients with AD were separated from those with PDD using a
      combination of p-tau, FABP3, and alpha-syn (AUC 0.96). CSF FABP3 was inversely
      associated with Mini Mental State Examination score in the whole cohort (r = 
      0.42, p < 0.001). CONCLUSIONS: The combination of CSF biomarkers linked to
      different aspects of neurodegeneration, such as FABP3, alpha-syn, and AD
      biomarkers, improves the biochemical characterization of AD and Lewy body
      disorders.

PMID- 28750676
TI  - Evaluation of a bespoke training to increase uptake by midwifery teams of NICE
      Guidance for membrane sweeping to reduce induction of labour: a stepped wedge
      cluster randomised design.
AB  - BACKGROUND: National guidance recommends pregnant women are offered membrane
      sweeping at term to reduce induction of labour. Local audit suggested this was
      not being undertaken routinely across two maternity units in the West Midlands,
      UK between March and November 2012. METHODS: Bespoke training session for
      midwifery teams (nine community and one antenatal clinic) was developed to
      address identified barriers to encourage offer of membrane sweeping, together
      with an information leaflet for women and appointment of a champion within each
      team. The timing of training session on membrane sweeping to ten midwifery teams
      was randomly allocated using a stepped wedge cluster randomised design. All women
      who gave birth in the Trusts after 39 + 3/40 weeks gestation within the study
      time period were eligible. Relevant anonymised data were extracted from maternity
      notes for three months before and after training. Data were analysed using a
      generalised linear mixed model, allowing for clustering and adjusting for
      temporal effects. Primary outcomes were number of women offered and accepting
      membrane sweeping and average number of sweeps per woman. Sub-group comparisons
      were undertaken for adherence to Trust guidance and potential influence of pre
      specified maternal characteristics. Data included whether sweeping was offered
      but declined and no record of membrane sweeping. RESULTS: Training was given to
      all teams as planned. Analyses included data from 2787 of the 2864 (97%) eligible
      low-risk women over 39 + 4 weeks pregnant. Characteristics of the women were
      similar before and after training. No evidence of difference in proportion of
      women being offered and accepting membrane sweeping (44.4% before training versus
      46.8% after training (adjusted relative risk [aRR] = 0.90, 95% confidence
      interval [CI] = 0.71-1.13), nor in average number of sweeps per woman (0.603
      versus 0.627, aRR = 0.83, 95% CI = 0.67-1.01). No differences in any secondary
      outcomes nor influence of maternal characteristics were demonstrated. The
      midwives evaluated training positively. CONCLUSIONS: This stepped wedge cluster
      trial enabled randomised evaluation within a natural roll-out and demonstrates
      the importance of robust evaluation in circumstances in which it is rarely
      undertaken. While the midwives evaluated the training positively, it did not
      appear to change practice. TRIALS REGISTRATION: ISRCTN14300475 . Registered on 23
      August 2016.

PMID- 28750677
TI  - Inhaled AP301 for treatment of pulmonary edema in mechanically ventilated
      patients with acute respiratory distress syndrome: a phase IIa randomized placebo
      controlled trial.
AB  - BACKGROUND: High-permeability pulmonary edema is a hallmark of acute respiratory
      distress syndrome (ARDS) and is frequently accompanied by impaired alveolar fluid
      clearance (AFC). AP301 enhances AFC by activating epithelial sodium channels
      (ENaCs) on alveolar epithelial cells, and we investigated its effect on
      extravascular lung water index (EVLWI) in mechanically ventilated patients with
      ARDS. METHODS: Forty adult mechanically ventilated patients with ARDS were
      included in a randomized, double-blind, placebo-controlled trial for proof of
      concept. Patients were treated with inhaled AP301 (n = 20) or placebo (0.9% NaCl;
      n = 20) twice daily for 7 days. EVLWI was measured by thermodilution (PiCCO(r)),
      and treatment groups were compared using the nonparametric Mann-Whitney U test.
      RESULTS: AP301 inhalation was well tolerated. No differences in mean baseline
      adjusted change in EVLWI from screening to day 7 were found between the AP301 and
      placebo group (p = 0.196). There was no difference in the PaO2/FiO2 ratio,
      ventilation pressures, Murray lung injury score, or 28-day mortality between the
      treatment groups. An exploratory subgroup analysis according to severity of
      illness showed reductions in EVLWI (p = 0.04) and ventilation pressures (p <
      0.05) over 7 days in patients with initial sequential organ failure assessment
      (SOFA) scores >=11 inhaling AP301 versus placebo, but not in patients with SOFA
      scores <=10. CONCLUSIONS: There was no difference in mean baseline-adjusted EVLWI
      between the AP301 and placebo group. An exploratory post-hoc subgroup analysis
      indicated reduced EVLWI in patients with SOFA scores >=11 receiving AP301. These
      results suggest further confirmation in future clinical trials of inhaled AP301
      for treatment of pulmonary edema in patients with ARDS. TRIAL REGISTRATION: The
      study was prospectively registered at clinicaltrials.gov, NCT01627613 .
      Registered 20 June 2012.

PMID- 28750678
TI  - Effects of urban motorways on physical activity and sedentary behaviour in local
      residents: a natural experimental study.
AB  - BACKGROUND: There is little evidence on how changing the physical environment
      changes health-related behaviours. We studied the effects of the new M74 motorway
      (freeway) - opened in 2011 - and the existing M8 motorway in Glasgow, Scotland,
      on physical activity and sedentary behaviour among local residents. METHODS: This
      natural experimental study used baseline (T1; 2005) and follow-up data (T2; 2013)
      from a longitudinal cohort (N = 365) and two cross-sectional samples (T1 N = 980;
      T2 N = 978). Adult participants were recruited from three study areas: one
      surrounding the new motorway, one surrounding the existing motorway, and a third,
      control, area without a motorway. The outcomes were self-reported time spent
      sitting, walking, and in moderate-to-vigorous physical activity (MVPA). Motorway
      exposure was defined in terms of (1) study area and (2) distance from home to the
      nearest motorway junction. Outcomes were regressed on exposures in two-part
      (walking and MVPA) or linear (sedentary behaviour) cohort and repeat cross
      sectional models, adjusted for baseline behaviour and sociodemographic
      covariates. RESULTS: Cohort participants living in the M8 area were less likely
      to participate in MVPA at follow-up than those living in the area without a
      motorway (OR 0.37; 95%CI 0.15, 0.91). Within the M8 area, those living closer to
      the motorway were also less likely to do so (OR 0.30; 95%CI 0.09, 0.97). No other
      statistically significant results were found. CONCLUSIONS: We found some evidence
      of a negative association between exposure to an existing urban motorway and
      MVPA. However, the behavioural impacts of motorways are likely to be complex and
      evolve over time.

PMID- 28750679
TI  - miR-500a-3p promotes cancer stem cells properties via STAT3 pathway in human
      hepatocellular carcinoma.
AB  - BACKGROUND: miR-500a-3p has been demonstrated to be involved in the development,
      progression and metastasis in several human cancers. Constitutive activation of
      JAK/STAT3 signaling pathway has been reported to play an important role in the
      development and progression of hepatocellular carcinoma (HCC).The purpose of this
      study was to determine the biological roles and clinical significance of miR-500a
      3p in HCC and to identify whether miR-500a-3p has an effect on the activity of
      JAK/STAT3 signaling in HCC. METHODS: miR-500a-3p expression was examined by real
      time PCR in 8 paired HCC tissues and individual 120 HCC tissues respectively.
      Statistical analysis was performed to explore the clinical correlation between
      miR-500a-3p expression and clinicopathological features and overall and relapse
      free survival in HCC patients. In vitro and in vivo assays were performed to
      investigate the biological roles of miR-500a-3p in HCC. The bioinformatics
      analysis, real-time PCR, western blot and luciferase reporter assay were
      performed to discern and examine the relationship between miR-500a-3p and its
      potential targets. Clinical correlation of miR-500a-3p with its targets was
      examined in HCC tissues. RESULTS: miR-500a-3p is dramatically elevated in HCC
      tissues and cells and high expression of miR-500a-3p correlates with poor overall
      and relapse-free survival in HCC patients. Upregulating miR-500a-3p enhances,
      while silencing miR-500a-3p suppresses, the spheroid formation ability, fraction
      of side population and expression of cancer stem cell factors in vitro and
      tumorigenicity in vivo in HCC cells. Our findings further reveal miR-500a-3p
      promotes the cancer stem cell characteristics via targeting multiple negative
      regulators of JAK/STAT3 signaling pathway, including SOCS2, SOCS4 and PTPN11,
      leading to constitutive activation of STAT3 signaling. Moreover, the inhibitory
      effects of anti-miR-500a-3p on cancer stem cell phenotypes and activity of STAT3
      signaling were reversed by silencing SOCS2, SOCS4 and PTPN11 in miR-500a-3p
      downexpressing cells, respectively. Clinical correlation of miR-500a-3p with the
      targets was examined in human HCC tissues. CONCLUSION: our results uncover a
      novel mechanism by which miR-500a-3p promotes the stemness maintenance of cancer
      stem cell in HCC, suggesting that silencing miR-500a-3p may serve as a new
      therapeutic strategy in the treatment of hepatocellular carcinoma.

PMID- 28750680
TI  - Primary tumor location as a predictor of the benefit of palliative resection for
      colorectal cancer with unresectable metastasis.
AB  - BACKGROUND: It is still under debate that whether stage IV colorectal cancer
      patients with unresectable metastasis can benefit from primary tumor resection,
      especially for asymptomatic colorectal cancer patients. Retrospective studies
      have shown controversial results concerning the benefit from surgery. This
      retrospective study aims to evaluate whether the site of primary tumor is a
      predictor of palliative resection in asymptomatic stage IV colorectal cancer
      patients. METHODS: One hundred ninety-four patients with unresectable metastatic
      colorectal cancer were selected from Sun Yat-sen University Cancer Center
      Database in the period between January 2007 and December 2013. All information
      was carefully reviewed and collected, including the treatment, age, sex,
      carcinoembryonic antigen, site of tumor, histology, cancer antigen 199, number of
      liver metastases, and largest diameter of liver metastasis. The univariate and
      multivariate analyses were used to detect the relationship between primary tumor
      resection and overall survival of unresectable stage IV colorectal cancer
      patients. RESULTS: One hundred twenty-five received palliative resection, and 69
      received only chemotherapy. Multivariate analysis indicated that primary tumor
      site was one of the independent factors (RR 0.569, P = 0.007) that influenced
      overall survival. For left-side colon cancer patients, primary tumor resection
      prolonged the median overall survival time for 8 months (palliative resection vs.
      no palliative resection: 22 vs. 14 months, P = 0.009); however, for right-side
      colon cancer patients, palliative resection showed no benefit (12 vs. 10 months,
      P = 0.910). CONCLUSIONS: This study showed that left-side colon cancer patients
      might benefit from the primary tumor resection in terms of overall survival. This
      result should be further explored in a prospective study.

PMID- 28750681
TI  - Drug-induced amino acid deprivation as strategy for cancer therapy.
AB  - Cancer is caused by uncontrollable growth of neoplastic cells, leading to
      invasion of adjacent and distant tissues resulting in death. Cancer cells have
      specific nutrient(s) auxotrophy and have a much higher nutrient demand compared
      to normal tissues. Therefore, different metabolic inhibitors or nutrient
      depleting enzymes have been tested for their anti-cancer activities. We review
      recent available laboratory and clinical data on using various specific amino
      acid metabolic pathways inhibitors in treating cancers. Our focus is on
      glutamine, asparagine, and arginine starvation. These three amino acids are
      chosen due to their better scientific evidence compared to other related
      approaches in cancer treatment. Amino acid-specific depleting enzymes have been
      adopted in different standard chemotherapy protocols. Glutamine starvation by
      glutaminase inhibitior, transporter inhibitor, or glutamine depletion has shown
      to have significant anti-cancer effect in pre-clinical studies. Currently,
      glutaminase inhibitor is under clinical trial for testing anti-cancer efficacy.
      Clinical data suggests that asparagine depletion is effective in treating
      hematologic malignancies even as a single agent. On the other hand, arginine
      depletion has lower toxicity profile and can effectively reduce the level of pro
      cancer biochemicals in patients as shown by ours and others' data. This supports
      the clinical use of arginine depletion as anti-cancer therapy but its exact
      efficacy in various cancers requires further investigation. However, clinical
      application of these enzymes is usually hindered by common problems including
      allergy to these foreign proteins, off-target cytotoxicity, short half-life and
      rapidly emerging chemoresistance. There have been efforts to overcome these
      problems by modifying the drugs in different ways to circumvent these hindrance
      such as (1) isolate human native enzymes to reduce allergy, (2) isolate enzyme
      isoforms with higher specificities and efficiencies, (3) pegylate the enzymes to
      reduce allergy and prolong the half-lives, and (4) design drug combinations
      protocols to enhance the efficacy of chemotherapy by drug synergy and minimizing
      resistance. These improvements can potentially lead to the development of more
      effective anti-cancer treatment with less adverse effects and higher therapeutic
      efficacy.

PMID- 28750682
TI  - Behavioural and neuroanatomical correlates of auditory speech analysis in primary
      progressive aphasias.
AB  - BACKGROUND: Non-verbal auditory impairment is increasingly recognised in the
      primary progressive aphasias (PPAs) but its relationship to speech processing and
      brain substrates has not been defined. Here we addressed these issues in patients
      representing the non-fluent variant (nfvPPA) and semantic variant (svPPA)
      syndromes of PPA. METHODS: We studied 19 patients with PPA in relation to 19
      healthy older individuals. We manipulated three key auditory parameters-temporal
      regularity, phonemic spectral structure and prosodic predictability (an index of
      fundamental information content, or entropy)-in sequences of spoken syllables.
      The ability of participants to process these parameters was assessed using two
      alternative, forced-choice tasks and neuroanatomical associations of task
      performance were assessed using voxel-based morphometry of patients' brain
      magnetic resonance images. RESULTS: Relative to healthy controls, both the nfvPPA
      and svPPA groups had impaired processing of phonemic spectral structure and
      signal predictability while the nfvPPA group additionally had impaired processing
      of temporal regularity in speech signals. Task performance correlated with
      standard disease severity and neurolinguistic measures. Across the patient
      cohort, performance on the temporal regularity task was associated with grey
      matter in the left supplementary motor area and right caudate, performance on the
      phoneme processing task was associated with grey matter in the left supramarginal
      gyrus, and performance on the prosodic predictability task was associated with
      grey matter in the right putamen. CONCLUSIONS: Our findings suggest that PPA
      syndromes may be underpinned by more generic deficits of auditory signal
      analysis, with a distributed cortico-subcortical neuraoanatomical substrate
      extending beyond the canonical language network. This has implications for
      syndrome classification and biomarker development.

PMID- 28750684
TI  - Clozapine-induced, dilated cardiomyopathy: a case report.
AB  - BACKGROUND: Clozapine is known to be a highly effective antipsychotic agent and
      additionally provides a significant reduction in suicide-risk and aggression.
      Clozapine-induced cardiomyopathy is a very rare but nonetheless dangerous side
      effect, with an incidence of 0.02-0.1%, depending on the literature, and a
      mortality rate of up to 17.9%. CASE PRESENTATION: We report on the case of a 25
      year-old patient, who was admitted for the evaluation of a potential
      electroconvulsive therapy due to persistent auditory hallucinations under
      clozapine. Shortly after admission he was found to be suffering from dilated
      cardiomyopathy, likely caused by his antipsychotic treatment. CONCLUSION:
      Clozapine-induced cardiomyopathy should be taken into account when monitoring
      patients treated with this antipsychotic and regular electrocardiograms should be
      performed in order to detect possible alterations as soon as possible.

PMID- 28750683
TI  - Identification of novel prostate cancer drivers using RegNetDriver: a framework
      for integration of genetic and epigenetic alterations with tissue-specific
      regulatory network.
AB  - We report a novel computational method, RegNetDriver, to identify tumorigenic
      drivers using the combined effects of coding and non-coding single nucleotide
      variants, structural variants, and DNA methylation changes in the DNase I
      hypersensitivity based regulatory network. Integration of multi-omics data from
      521 prostate tumor samples indicated a stronger regulatory impact of structural
      variants, as they affect more transcription factor hubs in the tissue-specific
      network. Moreover, crosstalk between transcription factor hub expression
      modulated by structural variants and methylation levels likely leads to the
      differential expression of target genes. We report known prostate tumor
      regulatory drivers and nominate novel transcription factors (ERF, CREB3L1, and
      POU2F2), which are supported by functional validation.

PMID- 28750685
TI  - Osteoradionecrosis of the hyoid bone after intra-arterial chemoradiotherapy for
      oropharyngeal cancer: MR imaging findings.
AB  - BACKGROUND: Osteoradionecrosis (ORN) of the hyoid bone sometimes induces severe
      front neck infection and can cause laryngeal stenosis and carotid rupture.
      Although ORN of the hyoid bone is known to be a complication of chemoradiotherapy
      for head and neck cancer, there has been no basis for its evaluation. Our purpose
      is to present the clinical and MR imaging features of ORN of the hyoid bone.
      METHODS: The study group comprised patients with advanced oropharyngeal cancer
      treated with targeted intra-arterial cisplatin infusion with concomitant
      radiotherapy. ORN of the hyoid bone was identified on the basis of decreased
      signal intensity of the bone marrow on T1WI images. Signal intensity on T2WI
      images was used to distinguish between inflammation and fibrosis. RESULTS: A
      total of 39 pre-treatment MR images and follow-up MR images were reviewed. ORN of
      the hyoid bone were detected in 30% of patients after treatment, with 23% of them
      showing inflammation and 7.7% fibrosis. Two patients developed severe neck
      infection and received antibiotics and underwent surgical intervention by
      tracheostomy and resection of the hyoid bone. CONCLUSION: Our MR imaging study
      showed that ORN of the hyoid bone is not particularly rare in patients with
      oropharyngeal cancer treated with chemoradiotherapy. Clinicians should evaluate
      images carefully to prevent the development of severe complication due to
      infection associated with ORN of the hyoid bone.

PMID- 28750686
TI  - Carbon dioxide narcosis due to inappropriate oxygen delivery: a case report.
AB  - BACKGROUND: Oxygen delivery to patients with chronic obstructive pulmonary
      disease may be challenging because of their potential hypoxic ventilatory drive.
      However, some oxygen delivery systems such as non-rebreathing face masks with an
      oxygen reservoir bag require high oxygen flow for adequate oxygenation and to
      avoid carbon dioxide rebreathing. CASE PRESENTATION: A 72-year-old Caucasian man
      with severe chronic obstructive pulmonary disease was admitted to the emergency
      department because of worsening dyspnea and an oxygen saturation of 81% measured
      by pulse oximetry. Oxygen was administered using a non-rebreathing mask with an
      oxygen reservoir bag attached. For fear of removing the hypoxic stimulus to
      respiration the oxygen flow was inappropriately limited to 4L/minute. The patient
      developed carbon dioxide narcosis and had to be intubated and mechanically
      ventilated. CONCLUSIONS: Non-rebreathing masks with oxygen reservoir bags must be
      fed with an oxygen flow exceeding the patient's minute ventilation (>6-10
      L/minute.). If not, the amount of oxygen delivered will be too small to
      effectively increase the arterial oxygen saturation. Moreover, the risk of carbon
      dioxide rebreathing dramatically increases if the flow of oxygen to a non
      rebreathing mask is lower than the minute ventilation, especially in patients
      with chronic obstructive pulmonary disease and low tidal volumes. Non-rebreathing
      masks (with oxygen reservoir bags) must be used cautiously by experienced medical
      staff and with an appropriately high oxygen flow of 10-15 L/minute. Nevertheless,
      arterial blood gases must be analyzed regularly for early detection of a rise in
      partial pressure of carbon dioxide in arterial blood in patients with chronic
      obstructive pulmonary disease  and a hypoxic ventilatory drive. These patients
      are more safely managed using a nasal cannula with an oxygen flow of 1-2L/minute
      or a simple face mask with an oxygen flow of 5L/minute.

PMID- 28750687
TI  - Extracellular vesicles from human liver stem cells restore argininosuccinate
      synthase deficiency.
AB  - BACKGROUND: Argininosuccinate synthase (ASS)1 is a urea cycle enzyme that
      catalyzes the conversion of citrulline and aspartate to argininosuccinate.
      Mutations in the ASS1 gene cause citrullinemia type I, a rare autosomal recessive
      disorder characterized by neonatal hyperammonemia, elevated citrulline levels,
      and early neonatal death. Treatment for this disease is currently restricted to
      liver transplantation; however, due to limited organ availability, substitute
      therapies are required. Recently, extracellular vesicles (EVs) have been reported
      to act as intercellular transporters carrying genetic information responsible for
      cell reprogramming. In previous studies, we isolated a population of stem cell
      like cells known as human liver stem cells (HLSCs) from healthy liver tissue.
      Moreover, EVs derived from HLSCs were reported to exhibit regenerative effects on
      the liver parenchyma in models of acute liver injury. The aim of this study was
      to evaluate whether EVs derived from normal HLSCs restored ASS1 enzymatic
      activity and urea production in hepatocytes differentiated from HLSCs derived
      from a patient with type I citrullinemia. METHODS: HLSCs were isolated from the
      liver of a patient with type I citrullinemia (ASS1-HLSCs) and characterized by
      fluorescence-activated cell sorting (FACS), immunofluorescence, and DNA
      sequencing analysis. Furthermore, their differentiation capabilities in vitro
      were also assessed. Hepatocytes differentiated from ASS1-HLSCs were evaluated by
      the production of urea and ASS enzymatic activity. EVs derived from normal HLSCs
      were purified by differential ultracentrifugation followed by floating density
      gradient. The EV content was analyzed to identify the presence of ASS1 protein,
      mRNA, and ASS1 gene. In order to obtain ASS1-depleted EVs, a knockdown of the
      ASS1 gene in HLSCs was performed followed by EV isolation from these cells.
      RESULTS: Treating ASS1-HLSCs with EVs from HLSCs restored both ASS1 activity and
      urea production mainly through the transfer of ASS1 enzyme and mRNA. In fact, EVs
      from ASS1-knockdown HLSCs contained low amounts of ASS1 mRNA and protein, and
      were unable to restore urea production in hepatocytes differentiated from ASS1
      HLSCs. CONCLUSIONS: Collectively, these results suggest that EVs derived from
      normal HLSCs may compensate the loss of ASS1 enzyme activity in hepatocytes
      differentiated from ASS1-HLSCs.

PMID- 28750688
TI  - The psychometric characteristics of the revised depression attitude questionnaire
      (R-DAQ) in Pakistani medical practitioners: a cross-sectional study of doctors in
      Lahore.
AB  - BACKGROUND: Depression is common mental health problem and leading contributor to
      the global burden of disease. The attitudes and beliefs of the public and of
      health professionals influence social acceptance and affect the esteem and help
      seeking of people experiencing mental health problems. The attitudes of
      clinicians are particularly relevant to their role in accurately recognising and
      providing appropriate support and management of depression. This study examines
      the characteristics of the revised depression attitude questionnaire (R-DAQ) with
      doctors working in healthcare settings in Lahore, Pakistan. METHODS: A cross
      sectional survey was conducted in 2015 using the revised depression attitude
      questionnaire (R-DAQ). A convenience sample of 700 medical practitioners based in
      six hospitals in Lahore was approached to participate in the survey. The R-DAQ
      structure was examined using Parallel Analysis from polychoric correlations.
      Unweighted least squares analysis (ULSA) was used for factor extraction. Model
      fit was estimated using goodness-of-fit indices and the root mean square of
      standardized residuals (RMSR), and internal consistency reliability for the
      overall scale and subscales was assessed using reliability estimates based on
      Mislevy and Bock (BILOG 3 Item analysis and test scoring with binary logistic
      models. Mooresville: Scientific Software, 55) and the McDonald's Omega statistic.
      Findings using this approach were compared with principal axis factor analysis
      based on Pearson correlation matrix. RESULTS: 601 (86%) of the doctors approached
      consented to participate in the study. Exploratory factor analysis of R-DAQ scale
      responses demonstrated the same 3-factor structure as in the UK development
      study, though analyses indicated removal of 7 of the 22 items because of weak
      loading or poor model fit. The 3 factor solution accounted for 49.8% of the
      common variance. Scale reliability and internal consistency were adequate: total
      scale standardised alpha was 0.694; subscale reliability for professional
      confidence was 0.732, therapeutic optimism/pessimism was 0.638, and generalist
      perspective was 0.769. CONCLUSIONS: The R-DAQ was developed with a predominantly
      UK-based sample of health professionals. This study indicates that this scale
      functions adequately and provides a valid measure of depression attitudes for
      medical practitioners in Pakistan, with the same factor structure as in the scale
      development sample. However, optimal scale function necessitated removal of
      several items, with a 15-item scale enabling the most parsimonious factor
      solution for this population.

PMID- 28750689
TI  - Peri-foci adipose-derived stem cells promote chemoresistance in breast cancer.
AB  - BACKGROUND: Mesenchymal stem cells in tumor microenvironment can influence
      therapeutic responses in various types of cancers. For triple negative breast
      cancer, chemotherapy remains the mainstay of standard treatment. Our aim was to
      investigate the correlation between human adipose-derived stem cells (hAdSCs) and
      chemoresistance in triple negative breast cancer. METHOD: Conditioned medium was
      collected from hAdSCs, which was isolated from breast cancer patients who had had
      breast mastectomy. The expression of selected CD markers was evaluated by flow
      cytometry to characterize hAdSCs. By array analyses of the secreted cytokines and
      chemokines of hAdSCs, we identified CXCL1 that mediated doxorubicin resistance
      and the expression of ATP-binding cassette transporters ABCG2 in TNBC. By
      microRNA microarray, the association between hAdSC-mediated doxorubicin
      resistance in TNBC was also revealed. RESULTS: Conditioned medium collected from
      hAdSCs elicited doxorubicin resistance and enhanced the expression of ABCG2,
      which is a transporter responsible for the efflux of doxorubicin. CXCL1 secreted
      by hAdSCs downregulated miR-106a expression in triple negative breast cancer, and
      resulted in ABCG2 upregulation and doxorubicin resistance. CONCLUSIONS: Our
      findings suggest that CXCL1 secreted by hAdSCs elicits doxorubicin resistance
      through miR-106a-mediated ABCG2 upregulation in triple negative breast cancer.
      These findings provide a better understanding of the importance of adipose
      derived stem cells in breast cancer microenvironment regarding to the development
      of chemoresistance and reveal the potential of discovering novel therapeutic
      strategies to overcome drug resistance in TNBC.

PMID- 28750691
TI  - The Use of Interpreters in Medical Triage during a Refugee Mass-Gathering
      Incident in Europe.
AB  - : Introduction During a refugees' mass-gathering incident in Kos Island, Greece,
      Medecins Sans Frontieres (MSF; Brussels, Belgium) teams provided emergency
      medical care. A case report of the event focusing on difficulties encountered by
      the interpreters during triage and emergency response was prepared. METHODS: Data
      collected during the event were reviewed from the patient's register and
      qualitative interviews were obtained from the MSF interpreters involved in the
      response. In addition, a description of the event and a literature review were
      included. RESULTS: Total consultations were 49 patients, mainly from Syria, with
      an average age of 25 years. During triage, 20 patients were tagged green with
      only minor injuries; 11 patients were tagged yellow, mostly due to heat
      exhaustion, but also a hypertensive crisis, a diabetic, a pregnant woman with
      abdominal pain, and a peptic ulcer exacerbation. The remaining 18 patients were
      tagged red and diagnosed with heat syncope, except from a case of epileptic
      seizures and an acute chest pain patient. Interpreters were insufficient in
      number to accompany each doctor and every nurse providing care during the event.
      In addition, they were constantly disturbed by both refugees and fellow medical
      team members demanding their service. Interpreters had to triage and prioritize
      where to go and for whom to interpret. CONCLUSION: Interpreters are an integral
      part of a proper refugee reception system. They should be included in authorities
      planning where mass gatherings of refugees are expected. Appropriate training may
      be needed for interpreters to develop skills useful in mass gatherings and
      similar prehospital settings in order to better coordinate with the medical team.
      Alexakis LC Papachristou A Baruzzi C Konstantinou A . The use of interpreters in
      medical triage during a refugee mass-gathering incident in Europe. Prehosp
      Disaster Med. 2017;32(6):684-687.

PMID- 28750692
TI  - Opioid Analgesics: Is it Time for Risk Stratification Prior to Use?

PMID- 28750690
TI  - Increased Abeta42-alpha7-like nicotinic acetylcholine receptor complex level in
      lymphocytes is associated with apolipoprotein E4-driven Alzheimer's disease
      pathogenesis.
AB  - BACKGROUND: The apolipoprotein E epsilon4 (APOE4) genotype is a prominent late
      onset Alzheimer's disease (AD) risk factor. ApoE4 disrupts memory function in
      rodents and may contribute to both plaque and tangle formation. METHODS:
      Coimmunoprecipitation and Western blot detection were used to determine: 1) the
      effects of select fragments from the apoE low-density lipoprotein (LDL) binding
      domain and recombinant apoE subtypes on amyloid beta (Abeta)42-alpha7 nicotinic
      acetylcholine receptor (alpha7nAChR) interaction and tau phosphorylation in
      rodent brain synaptosomes; and 2) the level of Abeta42-alpha7nAChR complexes in
      matched controls and patients with mild cognitive impairment (MCI) and dementia
      due to AD with known APOE genotypes. RESULTS: In an ex vivo study using rodent
      synaptosomes, apoE141-148 of the apoE promotes Abeta42-alpha7nAChR association
      and Abeta42-induced alpha7nAChR-dependent tau phosphorylation. In a single-blind
      study, we examined lymphocytes isolated from control subjects, patients with MCI
      and dementia due to AD with known APOE genotypes, sampled at two time points (1
      year apart). APOE epsilon4 genotype was closely correlated with heightened
      Abeta42-alpha7nAChR complex levels and with blunted exogenous Abeta42 effects in
      lymphocytes derived from AD and MCI due to AD cases. Similarly, plasma from APOE
      epsilon4 carriers enhanced the Abeta42-induced Abeta42-alpha7nAChR association in
      rat cortical synaptosomes. The progression of cognitive decline in APOE epsilon4
      carriers correlated with higher levels of Abeta42-alpha7nAChR complexes in
      lymphocytes and greater enhancement by their plasma of Abeta42-induced Abeta42
      alpha7nAChR association in rat cortical synaptosomes. CONCLUSIONS: Our data
      suggest that increased lymphocyte Abeta42-alpha7nAChR-like complexes may indicate
      the presence of AD pathology especially in APOE epsilon4 carriers. We show that
      apoE, especially apoE4, promotes Abeta42-alpha7nAChR interaction and Abeta42
      induced alpha7nAChR-dependent tau phosphorylation via its apoE141-148 domain.
      These apoE-mediated effects may contribute to the APOE epsilon4-driven
      neurodysfunction and AD pathologies.

PMID- 28750693
TI  - Influence of Diabetes on Long-Term Coronary Artery Bypass Graft Patency.
AB  - BACKGROUND: Nearly 50% of patients undergoing coronary artery bypass grafting
      have diabetes. However, little is known about the influence of diabetes on long
      term patency of bypass grafts. Because patients with diabetes have more severe
      coronary artery stenosis, we hypothesized that graft patency is worse in patients
      with than without diabetes. OBJECTIVES: This study sought to examine the
      influence of diabetes on long-term patency of bypass grafts. METHODS: From 1972
      to 2011, 57,961 patients underwent primary isolated coronary artery bypass
      grafting. Of these, 1,372 pharmacologically treated patients with diabetes and
      10,147 patients without diabetes had 15,887 postoperative angiograms; stenosis
      was quantified for 7,903 internal thoracic artery (ITA) grafts and 20,066
      saphenous vein grafts. Status of graft patency across time was analyzed by
      longitudinal nonlinear mixed-effects modeling. RESULTS: ITA graft patency was
      stable over time and similar in patients with and without diabetes: at 1, 5, 10,
      and 20 years, 97%, 97%, 96%, and 96% in patients with diabetes, and 96%, 96%,
      95%, and 93% in patients without diabetes, respectively (early p = 0.20; late p =
      0.30). In contrast, saphenous vein graft patency declined over time and similarly
      in patients with and without diabetes: at 1, 5, 10, and 20 years, 78%, 70%, 57%,
      and 42% in patients with diabetes, and 82%, 72%, 58%, and 41% in patients without
      diabetes, respectively (early p < 0.002; late p = 0.60). After adjusting for
      patient characteristics, diabetes was associated with higher early patency of ITA
      grafts (odds ratio: 0.63; 95% confidence limits: 0.43 to 0.91; p = 0.013), but
      late patency of ITA grafts was similar in patients with and without diabetes (p =
      0.80). Early and late patency of saphenous vein grafts were similar in patients
      with and without diabetes (early p = 0.90; late p = 0.80). CONCLUSIONS: Contrary
      to our hypothesis, diabetes did not influence long-term patency of bypass grafts.
      Use of ITA grafts should be maximized in patients undergoing coronary artery
      bypass grafting because they have excellent patency in patients with and without
      diabetes even after 20 years.

PMID- 28750694
TI  - Diabetes Status and Graft Patency After Coronary Bypass Surgery: Is There a
      Diabetes Paradox?

PMID- 28750696
TI  - Striking the Balance Between Benefits and Costs of Ticagrelor Beyond 1 Year After
      Myocardial Infarction.

PMID- 28750695
TI  - Cost-Effectiveness of Long-Term Ticagrelor in Patients With Prior Myocardial
      Infarction: Results From the PEGASUS-TIMI 54 Trial.
AB  - BACKGROUND: In patients with a myocardial infarction (MI) 1 to 3 years earlier,
      treatment with ticagrelor + low-dose aspirin (ASA) reduces the risk of
      cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone,
      but at an increased risk of major bleeding. OBJECTIVES: The authors evaluated
      cost-effectiveness of ticagrelor + low-dose ASA in patients with prior MI within
      the prior 3 years. METHODS: The authors performed a prospective economic substudy
      alongside the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients
      With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of
      Aspirin-Thrombolysis In Myocardial Infarction 54) trial, which randomized 21,162
      patients to ASA alone, ticagrelor 60 mg twice daily + low-dose ASA, or ticagrelor
      90 mg twice daily + low-dose ASA. Medical resource use data were collected over a
      median 33-month follow-up. Costs were assessed from the U.S. health care system
      perspective. In-trial data relating to survival, utility, and costs were combined
      with lifetime projections to evaluate lifetime cost-effectiveness of the Food and
      Drug Administration-approved lower-dose ticagrelor regimen (60 mg twice daily).
      RESULTS: Hospitalization costs were similar for ticagrelor 60 mg and placebo
      ($2,262 vs. $2,333; 95% confidence interval for difference -$303 to $163; p =
      0.54); after inclusion of a daily ticagrelor 60 mg cost of $10.52, total costs
      were higher for ticagrelor ($10,016 vs. $2,333; 95% CI: $7,441 to $7,930; p <
      0.001). In-trial quality-adjusted life-years (QALYs) were similar (2.28 vs. 2.27;
      p = 0.34). Over a lifetime horizon, ticagrelor was associated with QALY gains of
      0.078 and incremental costs of $7,435, yielding an incremental cost-effectiveness
      ratio (ICER) of $94,917/QALY gained. Several high-risk groups had more favorable
      ICERs, including patients with >1 prior MI, multivessel disease, diabetes, renal
      dysfunction (all with ICERs $50,000 to $70,000/QALY gained), patients age <75
      years (ICER = $44,779/QALY gained), and patients with peripheral artery disease
      (ICER = $13,427/QALY gained). CONCLUSIONS: For patients with a history of MI >1
      year previously, long-term treatment with ticagrelor 60 mg + low-dose ASA yields
      a cost-effectiveness ratio suggesting intermediate value based on current
      guidelines. Ticagrelor appears to provide higher value for patients in several
      recognized high-risk subgroups. (Prevention of Cardiovascular Events [e.g., Death
      From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior
      Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin
      [PEGASUS]; NCT01225562).

PMID- 28750697
TI  - Temperature-Controlled Radiofrequency Ablation for Pulmonary Vein Isolation in
      Patients With Atrial Fibrillation.
AB  - BACKGROUND: Saline irrigation improved the safety of radiofrequency (RF)
      ablation, but the thermal feedback for energy titration is absent. OBJECTIVES: To
      allow temperature-controlled irrigated ablation, a novel irrigated RF catheter
      was designed with a diamond-embedded tip (for rapid cooling) and 6 surface
      thermocouples to reflect tissue temperature. High-resolution electrograms (EGMs)
      from the split-tip electrode allowed rapid lesion assessment. The authors
      evaluated the preclinical and clinical performance of this catheter for pulmonary
      vein (PV) isolation. METHODS: Using the DiamondTemp (DT) catheter, pigs (n = 6)
      underwent discrete atrial ablation in a temperature control mode (60 degrees C/50
      W) until there was ~80% EGM amplitude reduction. In a single-center clinical
      feasibility study, 35 patients underwent PV isolation with the DT catheter (study
      group); patients were planned for PV remapping after 3 months, regardless of
      symptomatology. A control group included 35 patients who underwent PV isolation
      with a standard force-sensing catheter. RESULTS: Porcine lesion histology
      revealed transmurality in 51 of 55 lesions (92.7%). In patients, all PVs were
      successfully isolated; no char or thrombus formation was observed. Compared with
      the control group, the study cohort had shorter mean RF application duration
      (26.3 +/- 5.2 min vs. 89.2 +/- 27.2 min; p < 0.001), shorter mean fluoroscopic
      time (11.2 +/- 8.5 min vs. 19.5 +/- 6.8 min; p < 0.001), and lower acute dormant
      PV reconduction (0 of 35 vs. 5 of 35; p = 0.024). At 3 months, 23 patients
      underwent remapping: 39 of 46 PV pairs (84.8%) remained durably isolated in 17 of
      these patients (73.9%). CONCLUSIONS: This first-in-human series demonstrated that
      temperature-controlled irrigated ablation produced rapid, efficient, and durable
      PV isolation. (ACT DiamondTemp Temperature-Controlled and Contact Sensing RF
      Ablation Clinical Trial for Atrial Fibrillation [TRAC-AF]; NCT02821351).

PMID- 28750698
TI  - Power- Versus Temperature-Guided Radiofrequency Ablation: Have We Found the
      Perfect Catheter?

PMID- 28750700
TI  - High-Sensitivity Troponin in the General Population: Time for a New Normal?

PMID- 28750699
TI  - High-Sensitivity Cardiac Troponin Concentration and Risk of First-Ever
      Cardiovascular Outcomes in 154,052 Participants.
AB  - BACKGROUND: High-sensitivity assays can quantify cardiac troponins I and T (hs
      cTnI, hs-cTnT) in individuals with no clinically manifest myocardial injury.
      OBJECTIVES: The goal of this study was to assess associations of cardiac troponin
      concentration with cardiovascular disease (CVD) outcomes in primary prevention
      studies. METHODS: A search was conducted of PubMed, Web of Science, and EMBASE
      for prospective studies published up to September 2016, reporting on associations
      of cardiac troponin concentration with first-ever CVD outcomes (i.e., coronary
      heart disease [CHD], stroke, or the combination of both). Study-specific
      estimates, adjusted for conventional risk factors, were extracted by 2
      independent reviewers, supplemented with de novo data from PROSPER (Pravastatin
      in Elderly Individuals at Risk of Vascular Disease Study), then pooled by using
      random effects meta-analysis. RESULTS: A total of 28 relevant studies were
      identified involving 154,052 participants. Cardiac troponin was detectable in
      80.0% (hs-cTnI: 82.6%; hs-cTnT: 69.7%). In PROSPER, positive associations of log
      linear shape were observed between hs-cTnT and CVD outcomes. In the meta
      analysis, the relative risks comparing the top versus the bottom troponin third
      were 1.43 (95% confidence interval [CI]: 1.31 to 1.56) for CVD (11,763 events),
      1.67 (95% CI: 1.50 to 1.86) for fatal CVD (7,775 events), 1.59 (95% CI: 1.38 to
      1.83) for CHD (7,061 events), and 1.35 (95% CI: 1.23 to 1.48) for stroke (2,526
      events). For fatal CVD, associations were stronger in North American studies (p =
      0.010) and those measuring hs-cTnT rather than hs-cTnI (p = 0.027). CONCLUSIONS:
      In the general population, high cardiac troponin concentration within the normal
      range is associated with increased CVD risk. This association is independent of
      conventional risk factors, strongest for fatal CVD, and applies to both CHD and
      stroke.

PMID- 28750702
TI  - Evidence on Blood Pressure Measurement Methodology and Clinical Implementation:
      Research Agenda for the 21st Century.

PMID- 28750701
TI  - Accuracy of Cuff-Measured Blood Pressure: Systematic Reviews and Meta-Analyses.
AB  - BACKGROUND: Hypertension (HTN) is the single greatest cardiovascular risk factor
      worldwide. HTN management is usually guided by brachial cuff blood pressure (BP),
      but questions have been raised regarding accuracy. OBJECTIVES: This comprehensive
      analysis determined the accuracy of cuff BP and the consequent effect on BP
      classification compared with intra-arterial BP reference standards. METHODS:
      Three individual participant data meta-analyses were conducted among studies
      (from the 1950s to 2016) that measured intra-arterial aortic BP, intra-arterial
      brachial BP, and cuff BP. RESULTS: A total of 74 studies with 3,073 participants
      were included. Intra-arterial brachial systolic blood pressure (SBP) was higher
      than aortic values (8.0 mm Hg; 95% confidence interval [CI]: 5.9 to 10.1 mm Hg; p
      < 0.0001) and intra-arterial brachial diastolic BP was lower than aortic values (
      1.0 mm Hg; 95% CI: -2.0 to -0.1 mm Hg; p = 0.038). Cuff BP underestimated intra
      arterial brachial SBP (-5.7 mm Hg; 95% CI: -8.0 to -3.5 mm Hg; p < 0.0001) but
      overestimated intra-arterial diastolic BP (5.5 mm Hg; 95% CI: 3.5 to 7.5 mm Hg; p
      < 0.0001). Cuff and intra-arterial aortic SBP showed a small mean difference (0.3
      mm Hg; 95% CI: -1.5 to 2.1 mm Hg; p = 0.77) but poor agreement (mean absolute
      difference 8.0 mm Hg; 95% CI: 7.1 to 8.9 mm Hg). Concordance between BP
      classification using the Seventh Report of the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure cuff BP
      (normal, pre-HTN, and HTN stages 1 and 2) compared with intra-arterial brachial
      BP was 60%, 50%, 53%, and 80%, and using intra-arterial aortic BP was 79%, 57%,
      52%, and 76%, respectively. Using revised intra-arterial thresholds based on cuff
      BP percentile rank, concordance between BP classification using cuff BP compared
      with intra-arterial brachial BP was 71%, 66%, 52%, and 76%, and using intra
      arterial aortic BP was 74%, 61%, 56%, and 65%, respectively. CONCLUSIONS: Cuff BP
      has variable accuracy for measuring either brachial or aortic intra-arterial BP,
      and this adversely influences correct BP classification. These findings indicate
      that stronger accuracy standards for BP devices may improve cardiovascular risk
      management.

PMID- 28750705
TI  - Educating the MACRA-Ready Cardiologist: Developing Competencies in Value-Based
      Cardiovascular Medicine.

PMID- 28750704
TI  - Should We Still Have Bare-Metal Stents Available in Our Catheterization
      Laboratory?
AB  - The introduction of bare-metal stents (BMS) has represented a major advancement
      over plain old balloon angioplasty in the management of coronary artery disease.
      However, the high rates of target lesion revascularization associated with use of
      BMS have led to the development of drug-eluting stents, which require prolonged
      dual antiplatelet therapy due to the increased risk of late and very late stent
      thrombosis. The improvements in newer-generation drug-eluting stents have
      translated into better safety and efficacy compared with earlier generation and
      BMS, thus allowing shorter dual antiplatelet therapy duration. Here, we aim to
      provide reasons as to why we still need BMS in our cardiac catheterization
      laboratory.

PMID- 28750706
TI  - Real Clinical Significance of Statin Cessation After Adjustment for Smoking
      Persistence and Antiplatelet Treatment Discontinuation.

PMID- 28750703
TI  - Translational Perspective on Epigenetics in Cardiovascular Disease.
AB  - A plethora of environmental and behavioral factors interact, resulting in changes
      in gene expression and providing a basis for the development and progression of
      cardiovascular diseases. Heterogeneity in gene expression responses among cells
      and individuals involves epigenetic mechanisms. Advancing technology allowing
      genome-scale interrogation of epigenetic marks provides a rapidly expanding view
      of the complexity and diversity of the epigenome. In this review, the authors
      discuss the expanding landscape of epigenetic modifications and highlight their
      importance for future understanding of disease. The epigenome provides a
      mechanistic link between environmental exposures and gene expression profiles
      ultimately leading to disease. The authors discuss the current evidence for
      transgenerational epigenetic inheritance and summarize the data linking
      epigenetics to cardiovascular disease. Furthermore, the potential targets
      provided by the epigenome for the development of future diagnostics, preventive
      strategies, and therapy for cardiovascular disease are reviewed. Finally, the
      authors provide some suggestions for future directions.

PMID- 28750707
TI  - Statin Intolerance and the Obsession With Aggressive Cholesterol Lowering to
      Prevent Coronary Heart Disease.

PMID- 28750708
TI  - Reply: Statin Intolerance and Risk for Recurrent Myocardial Infarction, Coronary
      Heart Disease Events, and All-Cause Mortality.

PMID- 28750709
TI  - Adjustments of Electrocardiographic Criteria for the Diagnosis of Left
      Ventricular Hypertrophy.

PMID- 28750710
TI  - Rheumatoid Arthritis and Risk of Nonischemic Heart Failure: Closely Related
      Common Soil.

PMID- 28750711
TI  - Reply: Adjustments of Electrocardiographic Criteria for the Diagnosis of Left
      Ventricular Hypertrophy.

PMID- 28750712
TI  - Transfer of Patients with Fournier's Gangrene: In reply to Fujita.

PMID- 28750713
TI  - Referral Criteria for Treatment of Fournier's Gangrene at Specialized Centers.

PMID- 28750714
TI  - Did Isolated Limb Infusion Improve Limb Salvage Rate?

PMID- 28750715
TI  - Treatment of Soft Tissue Sarcoma: In reply to He and colleagues.

PMID- 28750716
TI  - McElmoyle's Shield Revisited.

PMID- 28750717
TI  - Ulcerative Colitis Can Be Safely Managed with Variant 2-Stage Ileal Pouch-Anal
      Anastomosis.

PMID- 28750718
TI  - August 2017 Featured Articles, Volume 225.

PMID- 28750719
TI  - Correction.

PMID- 28750721
TI  - Retraction notice.

PMID- 28750720
TI  - Retraction notice.

PMID- 28750722
TI  - Corrigendum to 'Mitofusin 2 ameliorates hypoxia-induced apoptosis via
      mitochondrial function and signaling pathways title of article' [International
      Journal of Biochemistry and Cell Biology 69 (2015) 29-40].

PMID- 28750724
TI  - Acquired heart disease in adults: what can a chest X-ray tell us?
AB  - : The last 25 to 30 years have seen enormous advances in imaging techniques for
      the diagnosis of heart disease (echocardiography, cardiac MRI, CT angiography,
      etc.). Nevertheless, the first imaging test done in patient with heart disease
      continues to be plain-film chest X-rays. This economical, widely available
      technique makes it possible to follow up patients with heart disease and even to
      assess the severity of disease in some cases. This article explains how to read a
      chest X-ray systematically and the radiologic signs that make possible to suspect
      heart disease; it also provides detailed information about the signs of heart
      failure and the meaning of cardiac calcifications. CONCLUSION: Plain-film chest X
      rays provide valuable additional information in the diagnosis and management of
      adult patients with heart disease.

PMID- 28750723
TI  - Intra-individual cognitive imbalance in ASD between perceptual reasoning and
      ambiguity-solving related to tool use: Comparison among children exhibiting ASD,
      AD/HD, and typical development.
AB  - OBJECTIVE: Several studies have suggested that objective deficits in the
      processing of abstract information in conjunction with an enhanced ability to
      process concrete information is a definitive characteristic of autism spectrum
      disorder (ASD). However, this cognitive imbalance is not necessarily clear in
      high-functioning autistic individuals who do not display absolute differences
      relative to typically developing (TD) populations. Thus, the purpose of this
      study was to identify this cognitive tendency in high-functioning autistic
      individuals using intra-individual cognitive comparisons. METHODS: The reaction
      times (RTs) of TD children, children with ASD, and children with attention
      deficit hyperactivity disorder (AD/HD) (n=17 in each group, mean age=11.9years,
      age range=9.8-15.8years) were compared using the Which/How-to-Apply Tools (W/HAT)
      test, which consists of tasks requiring the adaptive use of novel tools and
      familiar tools in atypical and typical situations. Differences in RTs between the
      atypical and typical trials ([A-T]) were used to assess intra-individual
      cognitive imbalances. RESULTS: As predicted, the [A-T] scores of the ASD group
      were significantly higher than those of the TD group even though the RTs in the
      atypical and typical trials did not differ. Additionally, the [A-T] values were
      significantly higher in the ASD group than in the AD/HD group, which indicates
      that the cognitive imbalance was specific to ASD individuals. No significant
      interaction was detected between the trial and subject group. CONCLUSIONS: The
      findings of this study demonstrate that a cognitive imbalance in ASD individuals
      may enhance the current understanding of the pathophysiology of this disorder,
      which is found in a range of individuals, including those with obvious cortical
      dysfunction to those with only intra-individual imbalances.

PMID- 28750725
TI  - Hydroxyapatite collagen scaffold with autologous bone marrow aspirate for
      mandibular condylar reconstruction.
AB  - PURPOSE: This study was designed with the aim to assess the efficiency of
      hydroxyapatite/collagen (HA/Col) bio-scaffold with bone marrow aspirate (BMA) to
      reconstruct mandibular condyle in patients with temporomandibular joint (TMJ)
      ankylosis. MATERIALS AND METHODS: Seven pediatric patients with TMJ ankylosis,
      who visited our outpatient clinic and whose parents opted for this procedure,
      were included in this study. After a history and clinical examination for TMJ
      movements, computed tomography (CT) scans were obtained. Interposition
      arthroplasty, with or without coronoidectomy, was performed to gain at least 35
      mm of mouth opening. A 2-ml quantity of BMA was aspirated from the posterior
      iliac crest. A HA/Col block was carved to shape the condyle, and was fixed to the
      ramus using a plate and screws. A collagen sponge soaked in BMA was interposed in
      between the graft and ramal end, and the temporal fascia was rotated between the
      glenoid fossa and graft. Physiotherapy was started on postoperative day 10. All
      patients were followed up for 1 year. Success was graded on the basis of the
      mouth opening and TMJ score based on efficiency of chewing, speech, activity,
      recreation, mood, and anxiety on a five-point ordinal scale. RESULTS: The mean
      age was 9.71 years (range 5-14 years), and the male-to-female ratio was 5:2. The
      mean preoperative mouth opening was 4.14 mm, which improved to 34.57 mm at 1-year
      follow-up. The mean protrusive movement improved from 0 to 2.86 mm. The mean
      success score was 4.43 out of 5. The mean TMJ score improved from 2.38 to 3.94.
      CONCLUSION: A HA/Col bio-scaffold with bone marrow aspirate is a safe and cost
      effective alternative for reconstruction of the mandibular condyle, particularly
      in growing individuals with high osteogenic potential.

PMID- 28750726
TI  - The challenges of GxE research: A rejoinder.

PMID- 28750727
TI  - Safety of Moderate Hypothermia for Perinatal Hypoxic-Ischemic Encephalopathy: A
      Meta-analysis.
AB  - BACKGROUND: We investigated the safety of therapeutic hypothermia during
      intervention in infants with hypoxic-ischemic encephalopathy (HIE). METHODS: The
      MEDLINE, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials
      from onset to November 30, 2016 were searched for studies on perinatal HIE.
      Randomized controlled trials comparing the use of therapeutic hypothermia with
      normothermia for perinatal HIE were included in the study. Safety and efficacy
      data for therapeutic hypothermia in 1806 infants with HIE were included in this
      meta-analysis. The primary outcomes were safety variables, and the secondary
      outcomes were efficacy variables. A fixed-effect model was used to perform the
      meta-analysis. Risk ratios (RR), risk differences (RD), and 95% confidence
      intervals (CI) were calculated. RESULTS: Thirteen trials, including 1806 infants,
      contained information on safety and efficacy variables. Moderate hypothermia
      significantly increased the risk of thrombocytopenia (RR 1.18, 95% CI 1.02 to
      1.37, P = 0.03; RD 0.06, 95% CI -0.02 to 0.09) and cardiac arrhythmia (RR 2.52,
      95% CI 1.62 to 3.93, P < 0.0001; RD 0.19, 95% CI 0.09 to 0.03) during
      intervention. CONCLUSIONS: In infants with HIE, the application of therapeutic
      hypothermia increases the risk of thrombocytopenia and cardiac arrhythmia during
      intervention.

PMID- 28750728
TI  - [Blood donation in the light of anthropology].
AB  - In his well-known Essai sur le don, French anthropologist Marcel Mauss has shown
      that in all societies, donation and exchange of gifts are part of people's
      commitments. Although systematically denied, that obligation is one of the main
      sources of sociability. In this respect, blood donation can be considered as a
      very common act, except that, since blood comes from human body, that act is, at
      the same time, very special and meaningful.

PMID- 28750729
TI  - [Preparation of sedation-analgesia procedures in spanish paediatric emergency
      departments: A descriptive study].
AB  - INTRODUCTION: The objective of this study was to describe the current practice
      regarding the preparation of the sedation-analgesia (SA) procedures performed in
      the paediatric emergency centres in Spain. MATERIAL AND METHODS: A multicentre,
      observational and prospective analytical study was carried out on the SA
      procedures that were performed on children under 18 years-old in 18 paediatric
      emergency departments between February 2015 and January 2016. RESULTS: A total of
      658 SA procedures were registered in 18 hospitals of Spain, most of them to
      children older than 24 months. The type of the procedure was: simple analgesia in
      57 (8.6%), sedation in 44 (6.7%), SA for a not very painful procedure in 275
      (41.8%), and SA for a very painful procedure in 282 (42.9%). Informed consent was
      requested in 98.6% of the cases. The written form was more frequently preferred
      in the group of patients that received SA for a very painful procedure (76.6%) in
      comparison to a painful procedure or to simple analgesia (62.9% and 54.4%,
      respectively, P<.001). The staff that most frequently performed the SA procedures
      were the paediatricians of the emergency departments (64.3%), followed by
      Paediatrics Residents (30.7%). The most frequent reasons for the SA were
      traumatological (35.9%) and surgical (28.4%). Fasting was observed in 81% of the
      cases. More than two-thirds (67.3%, n=480) children were monitored, the majority
      (95.8%) of them using pulse oximetry. The pharmacological strategy used was the
      administration of one drug in 443 (67.3%) of the cases, mostly nitrous oxide, and
      a combination of drugs in 215 (32.7%), especially midazolam/ketamine (46.9%).
      CONCLUSION: The majority of the SA procedures analysed in this study have been
      carried out correctly and prepared in accordance with the current guidelines.

PMID- 28750730
TI  - [Karyptype 48,XXXY/49,XXXXY and proximal radioulnar synostosis].

PMID- 28750731
TI  - A volatile tracer-assisted headspace analytical technique for determining the
      swelling capacity of superabsorbent polymers.
AB  - This paper reports on a new method for the determination of swelling capacity of
      superabsorbent polymers by a volatile tracer-assisted headspace gas
      chromatography (HS-GC). Toluene was used as a tracer and added to the solution
      for polymers swelling test. Based on the differences of the tracer partitioned
      between the vapor and hydrogel phase before and after the polymer's swelling
      capacity, a transition point (corresponding to the material swelling capacity)
      can be observed when plotting the GC signal of toluene vs. the ratio of solution
      added to polymers. The present method has good precision (RSD<2.1%) and good
      accuracy, in which the relative deference between the data measured by the HS-GC
      method and the reference method were within 8.0%. The present method is very
      suitable to be used for testing the swelling capacity of polymers at the elevated
      temperatures.

PMID- 28750732
TI  - Ni-functionalized submicron mesoporous silica particles as a sorbent for metal
      affinity chromatography.
AB  - In this research, a novel IMAC sorbent with high specificity for chlorine
      containing compounds was developed. Ni-functionalized monodisperse spherical
      mesoporous silica particles of 500+/-25nm diameter were synthesized and their
      metal affinity properties were studied with the use of diclofenac as the model
      substance. The particles were aggregatively stable in the pH range of 3-12. The
      sorbent demonstrated a high adsorption capacity (0.60+/-0.06MUg of DCF per 1mg of
      the sorbent) and high adsorption/desorption rate (20 and 5min was enough for the
      sorbent saturation and desorption of DCF, correspondingly). A mixture of eluents
      with addition of PFOS providing the almost complete recovery (98%) of diclofenac
      was first proposed. The monodispersity and the high sedimentation and aggregative
      stability of the particles provide the formation of a stable hydrosol even under
      ultrasound treatment which makes the mSiO2/Ni particles suitable for batch
      chromatography.

PMID- 28750733
TI  - Separation and identification of fatty acid esters of algal carotenoid
      metabolites in the freshwater mussel Dreissena bugensis, by liquid chromatography
      with ultraviolet/visible wavelength and mass spectrometric detectors in series.
AB  - LC with photodiode array and APCI-ion trap mass spectrometry has made it possible
      to tentatively identify 76 carotenyl fatty acid esters (cFAEs) in solvent
      extracts from Dreissena bugensis, collected from Lake Erie: 16 mono- and 33
      diFAEs of fucoxanthinol (FOH), and 27 diFAEs of mactraxanthin (MX). FOH and MX,
      previously identified in cFAE hydrolysates, were confirmed as parent carotenoids
      of the cFAEs, and as primary metabolites of fucoxanthin and violaxanthin,
      respectively, derived from diatoms and chlorophytes in the dreissenids' diet. The
      most abundant fatty acid substituents of cFAEs were 16:0 and 16:1; abundant fatty
      acid biomarkers were 16:1 and 20:5, from diatoms, and 17:0, from bacteria.
      Cleanup of solvent extracts by solid phase extraction (Florisil) was necessary to
      reduce neutral background lipids, which interfered with detection of MX-diFAEs by
      APCI(+), and detection of FOH-diFAEs by APCI(+/-). The FOH-monoFAEs, MX-diFAEs
      and FOH-diFAEs were found to elute in a well-defined chromatographic order, by
      two regression models for retention times increasing as a function of: i)
      increasing number of carbons but decreasing number of double bonds in the fatty
      acid and decreasing number of non-esterified OH-groups on the parent carotenoids;
      ii) increasing dispersive but decreasing polar and hydrogen-bonding interactions,
      described by solubility parameters calculated for each cFAE. The best separations
      of the dreissenid cFAEs, with free OH-groups decreasing from four to one, were
      achieved between 20 and 68min, using a C18-column and moderately polar mobile
      phase (acetone, water), to obtain a reverse-phase gradient with a 56% decrease in
      hydrogen-bonding interactions.

PMID- 28750734
TI  - GC-MS based metabolomics used for the identification of cancer volatile organic
      compounds as biomarkers.
AB  - A biomarker can be a metabolite, coming from a metabolic pathway or cell process,
      which might be employed in the diagnostic of diseases, predict patient response
      towards chemical therapies and/or monitor disease recurrences. Biomarkers, e.g.
      aldehydes or hydrocarbons, are often identified from different body fluids such
      as blood, urine, serum, saliva or from various tissues samples, and their
      concentration can vary from one sample to the other. However, the detection and
      the action of these biomarkers for diseases is a complicated process. Cancer is
      one of the main cause of death worldwide. The main characteristic of cancerous
      tumor is the uncontrolled growing of cells inside the organism. Likely, these
      uncontrolled growths are as consequence changes in the metabolism that could be
      analytically monitored. Depending on where the cancer cells are located, they
      provide different characteristics profiles. These profiles as fingerprints are
      used for differentiation in a comparison to normal cells. This critical study
      aimed at highlighting the latest progress in this area, especially in the
      employment of gas chromatography for the monitoring of volatile organic compounds
      (VOCs) and the identification of possible molecules used as biomarkers for cancer
      therapy.

PMID- 28750735
TI  - Treatment with Recombinant Human MG53 Protein Increases Membrane Integrity in a
      Mouse Model of Limb Girdle Muscular Dystrophy 2B.
AB  - Limb girdle muscular dystrophy type 2B (LGMD2B) and other dysferlinopathies are
      degenerative muscle diseases that result from mutations in the dysferlin gene and
      have limited treatment options. The dysferlin protein has been linked to multiple
      cellular functions including a Ca2+-dependent membrane repair process that
      reseals disruptions in the sarcolemmal membrane. Recombinant human MG53 protein
      (rhMG53) can increase the membrane repair process in multiple cell types both in
      vitro and in vivo. Here, we tested whether rhMG53 protein can improve membrane
      repair in a dysferlin-deficient mouse model of LGMD2B (B6.129-Dysftm1Kcam/J). We
      found that rhMG53 can increase the integrity of the sarcolemmal membrane of
      isolated muscle fibers and whole muscles in a Ca2+-independent fashion when
      assayed by a multi-photon laser wounding assay. Intraperitoneal injection of
      rhMG53 into mice before acute eccentric treadmill exercise can decrease the
      release of intracellular enzymes from skeletal muscle and decrease the entry of
      immunoglobulin G and Evans blue dye into muscle fibers in vivo. These results
      indicate that short-term rhMG53 treatment can ameliorate one of the underlying
      defects in dysferlin-deficient muscle by increasing sarcolemmal membrane
      integrity. We also provide evidence that rhMG53 protein increases membrane
      integrity independently of the canonical dysferlin-mediated, Ca2+-dependent
      pathway known to be important for sarcolemmal membrane repair.

PMID- 28750736
TI  - Obestatin Increases the Regenerative Capacity of Human Myoblasts Transplanted
      Intramuscularly in an Immunodeficient Mouse Model.
AB  - Although cell-based therapy is considered a promising method aiming at treating
      different muscular disorders, little clinical benefit has been reported. One of
      major hurdles limiting the efficiency of myoblast transfer therapy is the poor
      survival of the transplanted cells. Any intervention upon the donor cells focused
      on enhancing in vivo survival, proliferation, and expansion is essential to
      improve the effectiveness of such therapies in regenerative medicine. In the
      present work, we investigated the potential role of obestatin, an autocrine
      peptide factor regulating skeletal muscle growth and repair, to improve the
      outcome of myoblast-based therapy by xenotransplanting primary human myoblasts
      into immunodeficient mice. The data proved that short in vivo obestatin treatment
      of primary human myoblasts not only enhances the efficiency of engraftment, but
      also facilitates an even distribution of myoblasts in the host muscle. Moreover,
      this treatment leads to a hypertrophic response of the human-derived regenerating
      myofibers. Taken together, the activation of the obestatin/GPR39 pathway resulted
      in an overall improvement of the efficacy of cell engraftment within the host's
      skeletal muscle. These data suggest considerable potential for future therapeutic
      applications and highlight the importance of combinatorial therapies.

PMID- 28750738
TI  - Dengue Virus Evades AAV-Mediated Neutralizing Antibody Prophylaxis in Rhesus
      Monkeys.
AB  - Development of vaccines against mosquito-borne Flaviviruses is complicated by the
      occurrence of antibody-dependent enhancement (ADE), which can increase disease
      severity. Long-term delivery of neutralizing antibodies (nAbs) has the potential
      to effectively block infection and represents an alternative to vaccination. The
      risk of ADE may be avoided by using prophylactic nAbs harboring amino acid
      mutations L234A and L235A (LALA) in the immunoglobulin G (IgG) constant region.
      Here, we used recombinant adeno-associated viruses (rAAVs) to deliver the anti
      dengue virus 3 (DENV3) nAb P3D05. While the administration of rAAV-P3D05-rhesus
      immunoglobulin G1 (rhIgG1)-LALA to rhesus macaques engendered DENV3-neutralizing
      activity in serum, it did not prevent infection. The emergence of viremia
      following DENV3 challenge was delayed by 3-6 days in the rAAV-treated group, and
      replicating virus contained the envelope mutation K64R. This neutralization
      resistant variant was also confirmed by virus outgrowth experiments in vitro. By
      delivering P3D05 with unmutated Fc sequences, we further demonstrated that DENV3
      also evaded wild-type nAb prophylaxis, and serum viral loads appeared to be
      higher in the presence of low levels of unmutated P3D05-rhIgG1. Our study shows
      that a vectored approach for long-term delivery of nAbs with the LALA mutations
      is promising, but prophylaxis using a single nAb is likely insufficient at
      preventing DENV infection and replication.

PMID- 28750739
TI  - The YY1-HOTAIR-MMP2 Signaling Axis Controls Trophoblast Invasion at the Maternal
      Fetal Interface.
AB  - We aimed to determine the effect of YY1 expression on the expression profile of
      long noncoding RNAs (lncRNAs) in trophoblasts, and we studied the involvement of
      certain lncRNAs and YY1 in the pathogenesis of recurrent miscarriage (RM). RT2
      lncRNA PCR arrays revealed that YY1 overexpression in trophoblasts significantly
      promoted the expression of the HOX transcript antisense RNA HOTAIR and
      demonstrated that HOTAIR expression was significantly lower in the RM
      trophoblasts than in control trophoblasts. Ectopic HOTAIR overexpression and
      knockdown experiments revealed that it was a novel target of YY1. Bioinformatics
      analysis identified two YY1-binding sites in the HOTAIR promoter region, and
      chromatin immunoprecipitation (ChIP) analysis verified that YY1 binds directly to
      its promoter region. Interestingly, HOTAIR overexpression enhanced trophoblast
      invasion in an ex vivo explant culture model, while its knockdown repressed these
      effects. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      label-free quantitative proteomics screening revealed that HOTAIR overexpression
      activated phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling in
      trophoblasts. In an ex vivo explant culture model, HOTAIR overexpression
      effectively elevated matrix metalloproteinase 2 (MMP2) expression via the PI3K
      AKT signaling pathway, enhancing trophoblast migration and invasion. These
      findings reveal a new regulatory pathway in which YY1 activates PI3K-AKT
      signaling via HOTAIR, promoting MMP2 expression, suggesting that HOTAIR is a
      potential therapeutic target for RM.

PMID- 28750737
TI  - Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat
      Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis.
AB  - Despite aggressive antibiotic therapy, bronchopulmonary colonization by
      Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic
      fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with
      structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have
      demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a
      signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy
      for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of
      concept double-blind clinical trial. Submicromolar NO concentrations alone caused
      disruption of biofilms within ex vivo CF sputum and a statistically significant
      decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with
      ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation
      caused significant reduction in P. aeruginosa biofilm aggregates compared with
      placebo across 7 days of treatment. Our results suggest a benefit of using low
      dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to
      treat acute P. aeruginosa exacerbations in CF. Strategies to induce the
      disruption of biofilms have the potential to overcome biofilm-associated
      antibiotic tolerance in CF and other biofilm-related diseases.

PMID- 28750740
TI  - LncRNA ODRUL Contributes to Osteosarcoma Progression through the miR-3182/MMP2
      Axis.
AB  - Recent findings have shown that lncRNA dysregulation is involved in many cancers,
      including osteosarcoma (OS). In a previous study, we reported a novel lncRNA,
      ODRUL, that could promote doxorubicin resistance in OS. We now report the
      function and underlying mechanism of ODRUL in regulating OS progression. We show
      that ODRUL is upregulated in OS tissues and cell lines and correlates with poor
      prognosis. ODRUL knockdown significantly inhibits OS cell proliferation,
      migration, invasion, and tumor growth in vitro and in vivo by decreasing matrix
      metalloproteinase (MMP) expression. A microarray screen combined with online
      database analysis showed that miR-3182 is upregulated and MMP2 is downregulated
      in sh-ODRUL-expressing MG63 cells and that miR-3182 harbors potential binding
      sites for ODRUL and the 3' UTR of MMP2 mRNA. In addition, miR-3182 expression and
      function are inversely correlated with ODRUL expression in vitro and in vivo. A
      luciferase reporter assay demonstrated that ODRUL could directly interact with
      miR-3182 and upregulate MMP2 expression via its competing endogenous RNA activity
      on miR-3182 at the posttranscriptional level. Taken together, our study has
      elucidated the role of oncogenic ODRUL in OS progression and may provide a new
      target in OS therapy.

PMID- 28750741
TI  - Initiatives to fill the gaps in Africa's AIDS response.

PMID- 28750742
TI  - The effect of treatment simplification on HIV reservoirs.

PMID- 28750743
TI  - Methodological and statistical issues related to analysis of survival - Authors'
      reply.

PMID- 28750744
TI  - Methodological and statistical issues related to analysis of survival.

PMID- 28750745
TI  - Corrigendum to "A selective delta opioid receptor antagonist based on a stilbene
      core" [Bioorg. Med. Chem. Lett. 25 (2015) 5532-5535].

PMID- 28750746
TI  - Presentations from the Edwin L. Kendig Jr. Pediatric Pulmonary Symposium,
      Richmond Virginia May 25, 2017.

PMID- 28750747
TI  - Orientation-defined boundaries are detected with low efficiency.
AB  - When compared with other summary statistics (mean size, size variance,
      orientation variance), visual estimates of average orientation are inefficient.
      Observers act as if they use information from no more than two or three items. We
      hypothesised that observers would attain greater sampling efficiency when their
      task did not require an explicit representation of mean orientation. We tested
      this hypothesis using a texture-segmentation task. Two arrays of 32 wavelets each
      were presented; one left and one right of fixation. Orientations in the target
      array were sampled from wrapped normal distributions having two different means
      with the same variance. One distribution defined orientations above the
      horizontal meridian, the other defined orientations below the meridian. All
      orientations in the other array were defined by a single wrapped normal
      distribution having the same variance as each of the distributions in the target
      array. Contrary to our hypothesis, results indicate that observers effectively
      ignored all but one item from the top and bottom of each array. In fact, we found
      no change in the threshold difference between the target's two means when all but
      one item from the top and bottom of each array were removed. We are forced to
      conclude that the visual system does not compute the average of more than a few
      orientations, even for texture segmentation.

PMID- 28750748
TI  - Flash-lag effects in biological motion interact with body orientation and action
      familiarity.
AB  - The ability to localize moving joints of a person in action is crucial for
      interacting with other people in the environment. However, it remains unclear how
      the visual system encodes the position of joints in a moving body. We used a
      paradigm based on a well-known phenomenon, the flash-lag effect, to investigate
      the mechanisms underlying joint localization in bodily movements. We first found
      that observers perceived a strong flash-lag effect in biological motion: when a
      briefly-flashed dot was presented physically in perfect alignment with a
      continuously moving limb, the flash dot was perceived to lag behind the position
      of the moving joint. Importantly, our study revealed that for familiar forward
      walking actions, the strength of the flash-lag effect for a joint depends on body
      orientation. Specifically, observing a walker with a natural body orientation
      (i.e., upright) yielded a significantly stronger flash-lag effect for the
      critical foot joint than did viewing an inverted walker. In contrast, the hand
      joint showed a weaker flash-lag effect in the upright walker than the inverted
      walker. These findings suggest that the impact of body orientation on encoding
      joint locations depended on body part. Furthermore, we found that action
      familiarity modulates the impact of body orientation on the flash-lag effect.
      Body orientation impacted location encoding in familiar forward walking actions,
      but not in unfamiliar actions (e.g., backward walking, jumping-jack). Simulation
      results showed that generic motion mechanisms, such as the temporal averaging
      model, cannot fully account for these empirical findings regarding the flash-lag
      effect in biological motion. The present study provides compelling evidence that
      action processing interacts with position processing to localize the moving
      joints in whole-body actions, and that this influence depends on body orientation
      and familiarity of actions.

PMID- 28750749
TI  - Incidental focal colonic uptake in studies 18F-FDG PET/CT.
AB  - OBJECTIVES: To assess the frequency of focal colonic uptake as an incidental
      observation in 18F-FDG PET/CT studies, and to correlate this finding with
      histopathological results. MATERIAL AND METHODS: Out of a total of 3,176 PET/CT
      studies with 18F-FDG systematic analysis was carried out on 30 studies in which
      colonic focal uptake was observed. Patients with known colorectal neoplasia were
      excluded. The maximum standardised uptake values (SUVm) and the morphological
      findings provided by the CT were recorded. The studies were reported by a
      radiologist and a nuclear medicine doctor. The findings were compared with
      endoscopy and pathology findings. RESULTS: Of the 30 patients with focal
      hypermetabolic lesions of the colon (0.94%), 15 were men and 15 were women with
      ages between 27 and 73 (mean 55 years). The reasons for PET/CT were
      bronchopulmonary cancer (4), breast cancer (4), tumour of unknown origin (4),
      melanoma (3), renal carcinoma (3), cervical neoplasia (2), adenocarcinoma of
      ovary (2), and others (8). Of the 23 colonoscopies performed, 10 patients (43.4%)
      had malignant lesions, 6 (26.1%) had pre-malignant lesions, and in 7 patients
      (30.4%) no lesion was identified or was benign. No endoscopy was performed on 7
      patients for various reasons (patient refusal to perform the study, advanced
      oncological disease). An analysis was performed with the SUVm, with no
      statistically significant differences being found between malignant-premalignant
      lesions and benign lesions. CONCLUSIONS: Focal uptake in the colon of 18F-FDG has
      clinical relevance, and is mainly associated with morphological lesions in CT. It
      should be evaluated, as it may be a second tumour or a pre-malignant lesion. It
      is recommended that all focal uptakes of the colon be evaluated with endoscopy.

PMID- 28750750
TI  - Value of post-therapy 177Lu-PSMA images for accurate interpretation of therapy
      response with 68Ga-PSMA PET/CT.
AB  - A 54-year-old man with progressive prostate cancer underwent a 68Ga-PSMA PET/CT,
      which showed lymph node and bone metastases. After 2-cycles of 177Lu-PSMA
      therapy, the repeated 68Ga-PSMA PET/CT showed decreased radiotracer uptake in
      lymph node and bones metastases, but there were new lesions which may be
      compatible with progression or tumour sink-effect. A review of 177Lu-PSMA-therapy
      images revealed that new lesions in the second PET/CT were the metastatic lesions
      that progressed after the first PET/CT, and subsequently showed a good response.
      The patient received additional cycles of 177Lu-PSMA therapy, and the disease
      regressed further, with a PSA of 0.06ng/ml. Response evaluation of new
      therapeutic diagnostics (theranostic) agents needs a review of not only
      diagnostic PET/CT images, but also post-therapy images and laboratory results.

PMID- 28750751
TI  - The anti-aging and anti-oxidation effects of tea water extract in Caenorhabditis
      elegans.
AB  - Tea includes puer tea, black tea, green tea and many others. By using model
      organism Caenorhabditis elegans, the anti-aging and anti-oxidation effects of tea
      water extract were systemically examined in this study. We found that water
      extract of puer tea, black tea and green tea all increased the lifespan of worms,
      postponed Abeta-induced progressive paralysis in Alzheimer's disease transgenic
      worms, and improved the tolerance of worms to the oxidative stress induced by
      heavy metal Cr6+. Moreover, the anti-oxidation effects of tea water extract at
      low concentration were different among 4 kinds of brands of green tea. The
      underlying mechanisms were further explored using genetically manipulated-mutant
      worms. The anti-oxidative stress effects of green tea water extract depend on the
      dietary restriction and germline signaling pathways, but not the FOXO and
      mitochondrial respiratory chain signals. Therefore, tea water extract provides
      benefits of anti-aging, anti-AD and anti-oxidation.

PMID- 28750753
TI  - Photodynamic therapy with high-power LED mediated by erythrosine eliminates
      Enterococcus faecalis in planktonic forms.
AB  - BACKGROUND: The failure of endodontic treatment is linked to the presence of
      microorganisms, particularly Enterococcus faecalis, in the root canals. This
      study evaluated the effectiveness of photodynamic therapy (PDT) using erythrosine
      irradiated by a high-power curing light on a planktonic suspension culture of E.
      faecalis. METHODS: Bacterial suspensions of E. faecalis were adjusted and then
      mixed in a 1:1 proportion, in triplicate, in treatment groups by varying the
      length of irradiation time (120 and 240s) and the molarity of the erythrosine (5
      and 10MUM). In order to verify the post-treatment bactericidal effect, a count of
      the viable bacteria was performed (CFUmL-1) and transformed into Log10 CFU. The
      one-way ANOVA with Tukey post-hoc test was applied to check for differences
      between the groups. RESULTS: The bacteria were completely eradicated in the
      groups that used PDT with 5MUM 240s, 10MUM 120s and 10MUM 240s (p?0.001). The
      effect of the PDT 5MUM 120s group was significant (p?0.05) in comparison with the
      groups using only light or only erythrosine. Positive control (exposure to 2.5%
      NaClO for 120 and 240s) completely eradicated E. faecalis. The negative control
      (PBS) did not alter the quantities of E. faecalis CFU with 9.605 Log10 CFU at
      120s and 9.621 Log10 CFU at 240s. CONCLUSION: PDT with erythrosine in a
      concentration of 10MUM and high-power LED is capable of totally eliminating E.
      faecalis in planktonic suspension.

PMID- 28750752
TI  - Aging and circadian dysfunction increase alcohol sensitivity and exacerbate
      mortality in Drosophila melanogaster.
AB  - Alcohol abuse is a rising problem in middle-aged and older individuals resulting
      in serious health, family and economic consequences. Effective treatment
      necessitates the identification of factors influencing alcohol toxicity with
      aging. We investigated the interaction between aging, alcohol toxicity and
      circadian function using Drosophila as a model system. We found as wild type
      flies age, sensitivity to alcohol increases and circadian regulation of alcohol
      induced behaviors weakens. Decreased circadian modulation is correlated with
      significantly greater alcohol sensitivity during the subjective day. The
      circadian clock modulates alcohol-induced mortality in younger flies with
      increased mortality following alcohol exposure at night. Older flies exhibit
      significantly longer recovery times following alcohol-induced sedation and
      increased mortality following binge-like or chronic alcohol exposure. Flies
      rendered arrhythmic either genetically or environmentally exhibit significantly
      increased alcohol sensitivity, longer recovery times and increased mortality. We
      hypothesize that the circadian clock phase specifically buffers behavioral and
      cellular alcohol sensitivity with this protection diminishing as the circadian
      clock weakens with age.

PMID- 28750754
TI  - Physiological considerations acting on triplet oxygen for explicit dosimetry in
      photodynamic therapy.
AB  - The aims of this study were to determine the spatial and temporal theoretical
      distribution of the concentrations of Protoporphyrin IX, 3O2 and doses of 1O2.
      The type II mechanism and explicit dosimetry in photodynamic therapy were used.
      Furthermore, the mechanism of respiration and cellular metabolism acting on 3O2
      were taken into account. The dermis was considered as an absorbing and a
      scattering medium. An analytical solution was used for light diffusion in the
      skin. The photophysical, photochemical and biological effects caused by PDT with
      the initial irradiances of 20, 60 and 150mW/cm2 were studied for a time of
      exposure of 20min and a maximum depth of 0.5cm. We found that the initial
      irradiance triples its value in 0.02cm and that almost 100% of PpIX is part of
      the dynamics of reactions in photodynamic therapy. Additionally, with about
      40MUMof 3O2 there is a balance between the consumed and supplied oxygen. Finally,
      we determined that with 60mW/cm2, the highest dose of 1O2 is obtained.

PMID- 28750755
TI  - Evening salivary cortisol and alpha-amylase at 14months and neurodevelopment at
      4years: Sex differences.
AB  - Stress system activity in early life can have long-term effects on
      neurodevelopment. The main aim of this study was to assess the association of
      child evening salivary cortisol and alpha-amylase basal levels at 14months of age
      with longer-term neuropsychological development at 4years in a low-risk
      population-based birth cohort derived from the INMA (Environment and Childhood)
      project in Spain. We included 186 parent-children pairs with information on both
      stress system activity and neurodevelopment. Both stress markers at 14months of
      age showed an association with neuropsychological development at 4years. Salivary
      cortisol showed a sex-specific pattern of association. In girls, cortisol levels
      at 14months were negatively associated with cognitive development [long-term
      declarative memory (beta=-17.8, p=0.028; 95% CI=-33.2 to -2.5); executive
      function (beta=-9.8, p=0.08; 95% CI=-21 to 1)] and gross motor development (beta=
      13; p=0.022; 95% CI=-24 to -2), whereas in boys cortisol levels were negatively
      associated with socioemotional development [autistic-like behaviours: Incidence
      Rate Ratio (IRR)=1.6, p=0.039; 95% CI=1.01 to 2.41]. Salivary alpha-amylase was
      positively associated with socioemotional development in boys only [social
      competence (beta=2.11, p=0.013; 95% CI=0.47 to 3.72), autistic-like behaviours
      (IRR=0.93, p=0.042; 95% CI=0.87 to 0.99) and hyperactivity symptoms (IRR=0.81,
      p=0.021; 95% CI=0.69 to 0.97)]. These results suggest that stress system activity
      in early life is associated with longer-term neurodevelopment and that sex is an
      important factor in this relationship.

PMID- 28750757
TI  - Understanding the "terrible 2s" in preterm toddlers.

PMID- 28750756
TI  - Lessons from Goldilocks: maternal weight gain and neurocognitive outcomes of
      ELGAN.

PMID- 28750758
TI  - 50 Years Ago in The Journal of Pediatrics: The Denver Developmental Screening
      Test.

PMID- 28750759
TI  - Iron deficiency in adolescence.

PMID- 28750760
TI  - How mild is the outcome of mild neonatal encephalopathy?

PMID- 28750761
TI  - The next generation of Silver-Russell syndrome.

PMID- 28750762
TI  - When does BPD begin?

PMID- 28750763
TI  - 50 Years Ago in The Journal of Pediatrics: A Practical Classification of Newborn
      Infants by Weight and Gestational Age.

PMID- 28750764
TI  - Correction.

PMID- 28750765
TI  - To screen preterm brains at term or not: that is the question.

PMID- 28750766
TI  - 50 Years Ago in The Journal of Pediatrics: Further Observations on Trypsinogen
      Deficiency Disease: Report of a Second Case.

PMID- 28750767
TI  - 50 Years Ago in The Journal of Pediatrics: Acute Symptomatic Hyponatremia.

PMID- 28750768
TI  - Circulating levels of bacterial DNA and risk of infections in severe alcoholic
      hepatitis.

PMID- 28750769
TI  - Comparison of endoscopic therapies for rectal carcinoid tumors: Endoscopic
      mucosal resection with circumferential incision versus endoscopic submucosal
      dissection.
AB  - BACKGROUND AND OBJECTIVE: Although various endoscopic resection techniques have
      been established for rectal carcinoid tumors, there remains controversy regarding
      the best endoscopic treatment modality for these tumors. This study aimed to
      evaluate and compare the therapeutic efficacy and safety of EMR with
      circumferential incision (EMR-CI) and endoscopic submucosal dissection (ESD) for
      endoscopic resection of rectal carcinoid tumors. METHODS: From March 2012 to June
      2016, 66 rectal carcinoid tumors in 66 patients were resected by using EMR-CI
      (n=30) or ESD (n=36). The rates of both en bloc resection and complete resection,
      procedure time, procedure-related complications, and local or metastatic
      recurrence were analyzed retrospectively. RESULTS: The en bloc resection rate was
      96.7% (29/30) and 100% (36/36) for EMR-CI and ESD groups, respectively, and the
      difference was not statistically significant (P=0.455). The complete resection
      rate of the ESD group was 97.2% (35/36) and significantly higher than 76.7%
      (23/30) of the EMR-CI group (P=0.030). The mean procedure time of the ESD group
      was 20.44+/-6.64minutes, which was significantly longer than that of the EMR-CI
      group at 8.47+/-3.40minutes (P<0.001). The complication rates for ESD and EMR-CI
      did not differ significantly (0% for EMR-CI vs. 2.8% for ESD, P=1.000). No local
      or metastatic recurrence was found in either group during the follow-up period.
      CONCLUSION: This study suggested that ESD may be a safe, effective, and feasible
      endoscopic technique for removing rectal carcinoid tumors. ESD showed a similar
      safety profile and superior efficacy to EMR-CI.

PMID- 28750770
TI  - Circulating microRNAs panel as a diagnostic tool for discrimination of HCV
      associated hepatocellular carcinoma.
AB  - Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve the
      overall survival of HCC patients. However, current diagnostic markers are
      compromised and limited by their low sensitivity and specificity. In this work,
      circulating microRNAs (miRs) were utilized as a diagnostic tool to test their
      efficiency to segregate HCC and hepatitis C virus (HCV)-infected patients from
      healthy subjects. Nine HCC-related miRs (miR-21, miR-30c, miR-93, miR-122, miR
      125b, miR-126, miR-130a, miR-193b and miR-222) were analyzed by Real-Time PCR in
      86 serum samples; 34 HCC and 52 HCV patients in addition to 25 healthy subjects.
      The sensitivity and specificity of these miRs were assessed. Our results
      demonstrated that the median serum level of seven miRs was significantly reduced
      (P ranges from <0.01 to<0.001) in HCC patients whereas nine miRs were reduced
      (P<0.001) in HCV compared to healthy controls. Receiver operating characteristic
      (ROC) curve analyses had shown high diagnostic accuracy (AUC=1.0) when seven and
      nine combined miRs were considered in HCC and HCV groups, respectively compared
      to their counterparts. However, a combination of differentially expressed miRs
      did not improve the discriminatory power (AUC=0.742) when HCC compared to non-HCC
      groups. miR-122 showed the highest sensitivity and specificity to stratify HCC
      and HCV versus normal individuals and HCC versus HCV patients. We conclude that
      differentially expressed miRs in the serum of HCV and HCC patients can be
      utilized as surrogate and non-invasive biomarker for segregation of HCV and HCC
      patients from healthy subjects.

PMID- 28750771
TI  - Spatio-temporal expression of Mesocestoides corti McVAL2 during strobilar
      development.
AB  - VAL proteins belong to a diverse superfamily containing the CAP domain, with
      members described for various eukaryotic organisms, including parasites. They are
      implicated in diverse biological activities and, as secreted proteins, may be
      related in host - parasite interactions. For this reason they have been proposed
      as vaccine candidates against nematode infections. However, little is known about
      their function in cestodes. In M. corti, four partial cDNA sequences coding for
      members of the CAP superfamily were previously isolated. In this work we
      characterize the expression of McVAL2 in the larvae and segmented worms of M.
      corti, describing mRNA and protein localization using fluorescent microscopy. We
      also optimized real time PCR analysis for quantification of mRNA expression
      through the different stages of strobilar development. We show that McVAL2 is
      differentially located, depending on the developmental stage, and can be used as
      a molecular marker for the neuroendocrine system in the larvae. The dynamic and
      stage-specific expression patterns of McVAL2, combined with the large number of
      VAL proteins found in the genomes of parasitic flatworms, suggest varied roles
      for the VAL protein family in the biology of these parasites.

PMID- 28750772
TI  - Corrigendum to: Rhythmicity and cross-modal temporal Cues facilitate Detection
      [Neuropsychologia 63 (2014) 43-50].

PMID- 28750773
TI  - A study on current risk assessments and guidelines on the use of food animal
      products derived from cloned animals.
AB  - The author widely surveyed and analyzed the food safety issues, ethical issues,
      permits, and approval of animal products from animals cloned by somatic cell
      nuclear transfer worldwide. As a result of a 2-year survey, the author found that
      there is no evidence that meat and milk derived from cloned animals or their
      progeny pose a risk to food safety in terms of genotoxicity, adverse reproductive
      effects, or allergic reactions. Most countries have not approved meat and milk
      derived from cloned animals, and their progeny are entering the food supply. To
      establish the guidelines, the author suggests four principles of safety
      assessment for meat and milk derived from cloned animals. The four main
      principles for safety assessment are similarities of chemical composition,
      adverse reproductive effects, genotoxicity, and allergic reactions under the
      influence of meat and milk from cloned animals and noncloned counterparts. This
      principle means that meat and milk derived from a cloned animal are safe if there
      are no differences in the four safety assessments of meat and milk between cloned
      animal's progeny and noncloned counterparts.

PMID- 28750774
TI  - Effects of sub-chronic exposure to terbuthylazine on DNA damage, oxidative stress
      and parent compound/metabolite levels in adult male rats.
AB  - Terbuthylazine is a selective pre- and post-emergency chloro-triazine herbicide
      used for a broad spectrum of weed control. We evaluated the potential of low
      doses of terbuthylazine to induce oxidative stress and cytogenetic damage in
      peripheral blood samples of adult male Wistar rats. Following 28-day repeated
      oral exposure at 0.004 mg/kg b.w./day, 0.4 mg/kg b.w./day and 2.29 mg/kg
      b.w./day, parameters of lipid peroxidation, total antioxidant capacity, and
      activities of antioxidant enzymes were measured in blood samples. Alkaline comet
      assay on leukocytes and erythrocyte micronucleus assay were used to measure DNA
      damage. In addition, the concentration of terbuthylazine and its metabolite in
      urine and plasma were determined using high performance liquid chromatography
      with UV diode-array detector (HPLC-UV-DAD). The fraction of terbuthylazine
      excreted in urine was negligible and was not found in plasma.
      Deethylterbuthylazine was only compound detected in plasma samples. Exposure to
      terbuthylazine did not induce significant lipid peroxidation products. The
      significant changes in antioxidant enzyme activities and the elevated total
      antioxidant capacity indicated that terbuthylazine at experimental conditions
      applied has potential to disturb oxidative/antioxidant balance. Results regarding
      the alkaline comet assay as well as micronucleated reticulocyte frequency
      indicated that treatment led to low-level DNA instability. Our results call for
      further research using other sensitive biomarkers of effect, along with different
      exposure scenarios.

PMID- 28750775
TI  - Breakdown of long-range temporal correlations in brain oscillations during
      general anesthesia.
AB  - Consciousness has been hypothesized to emerge from complex neuronal dynamics,
      which prevails when brain operates in a critical state. Evidence supporting this
      hypothesis comes mainly from studies investigating neuronal activity on a short
      time-scale of seconds. However, a key aspect of criticality is presence of scale
      free temporal dependencies occurring across a wide range of time-scales. Indeed,
      robust long-range temporal correlations (LRTCs) are found in neuronal
      oscillations during conscious states, but it is not known how LRTCs are affected
      by loss of consciousness. To further test a relation between critical dynamics
      and consciousness, we investigated LRTCs in electrocorticography signals recorded
      from four macaque monkeys during resting wakefulness and general anesthesia
      induced by various anesthetics (ketamine, medetomidine, or propofol). Detrended
      Fluctuation Analysis was used to estimate LRTCs in amplitude fluctuations
      (envelopes) of band-pass filtered signals. We demonstrate two main findings.
      First, during conscious states all lateral cortical regions are characterized by
      significant LRTCs of alpha-band activity (7-14 Hz). LRTCs are stronger in the
      eyes-open than eyes-closed state, but in both states they form a spatial
      gradient, with anterior brain regions exhibiting stronger LRTCs than posterior
      regions. Second, we observed a substantial decrease of LRTCs during loss of
      consciousness, the magnitude of which was associated with the baseline (i.e. pre
      anesthesia) state of the brain. Specifically, brain regions characterized by
      strongest LRTCs during a wakeful baseline exhibited greatest decreases during
      anesthesia (i.e. "the rich got poorer"), which consequently disturbed the
      posterior-anterior gradient. Therefore, our results suggest that general
      anesthesia affects mainly brain areas characterized by strongest LRTCs during
      wakefulness, which might account for lack of capacities for extensive temporal
      integration during loss of consciousness.

PMID- 28750776
TI  - In vitro biofilm formation on resin-based composites after different finishing
      and polishing procedures.
AB  - OBJECTIVES: To evaluate the influence of surface treatments of different resin
      based composites (RBCs) on S. mutans biofilm formation. METHODS: 4 RBCs
      (microhybrid, nanohybrid, nanofilled, bulk-filled) and 6 finishing-polishing
      (F/P) procedures (open-air light-curing, light-curing against Mylar strip,
      aluminum oxide discs, one-step rubber point, diamond bur, multi-blade carbide
      bur) were evaluated. Surface roughness (SR) (n=5/group), gloss (n=5/group),
      scanning electron microscopy morphological analysis (SEM), energy-dispersive X
      ray spectrometry (EDS) (n=3/group), and S. mutans biofilm formation (n=16/group)
      were assessed. EDS analysis was repeated after the biofilm assay. A morphological
      evaluation of S. mutans biofilm was also performed using confocal laser-scanning
      microscopy (CLSM) (n=2/group). The data were analyzed using Wilcoxon (SR, gloss)
      and two-way ANOVA with Tukey as post-hoc tests (EDS, biofilm formation). RESULTS:
      F/P procedures as well as RBCs significantly influenced SR and gloss. While F/P
      procedures did not significantly influence S. mutans biofilm formation, a
      significant influence of RBCs on the same parameter was found. Different RBCs
      showed different surface elemental composition. Both F/P procedures and S. mutans
      biofilm formation significantly modified this parameter. CONCLUSIONS: The tested
      F/P procedures significantly influenced RBCs surface properties but did not
      significantly affect S. mutans biofilm formation. The significant influence of
      the different RBCs tested on S. mutans biofilm formation suggests that material
      characteristics and composition play a greater role than SR. CLINICAL
      SIGNIFICANCE: F/P procedures of RBCs may unexpectedly play a minor role compared
      to that of the restoration material itself in bacterial colonization.

PMID- 28750777
TI  - Prevalence of periodontitis, dental caries, and peri-implant pathology and their
      relation with systemic status and smoking habits: Results of an open-cohort study
      with 22009 patients in a private rehabilitation center.
AB  - OBJECTIVES: This investigation, based on a 3-year epidemiological surveillance
      open cohort study, aimed to provide an insight of the prevalence of
      periodontitis, dental caries and peri-implant pathology and to compare
      inferentially between healthy and systemic compromised patients. METHODS: A total
      of 22009 patients were observed consisting in 9035 men (41.1%) and 12974 women
      (58.9%) with an average age of 48.5 years (standard deviation of 15.6years). The
      prevalence of the 3 chronical oral diseases was calculated. The comparison
      between healthy and systemic compromised patients for each oral disease was
      performed through multivariate logistic regression: Odds ratios (OR) with 95%
      confidence intervals (95%CI) were estimated in one general model and one systemic
      condition specific model adjusted for age and gender. Attributable fractions were
      estimated for systemic conditions (both models). The level of significance was
      set at 5%. RESULTS: The prevalence rate of periodontitis, dental caries and peri
      implant pathology was 17.6%, 36.6% and 13.9%, respectively. The systemic
      compromised status was associated with the prevalence of the three chronical oral
      diseases on the general models. The systemic condition specific models yielded
      Diabetes [OR=1.49, 95%CI (1.24;1.79)] and HIV+ [OR=4.37, 95%CI (1.05;18.24)] as
      risk indicators for Periodontitis; cardiovascular conditions [OR=1.10, 95%CI
      (1.01;1.20)], Diabetes [OR=1.24, 95%CI (1.05;1.46)] and neurologic conditions
      [OR=1.84, 95%CI (1.32;2.57)] as risk indicators for dental caries; and smoking
      habits as a risk indicator for all three oral diseases [OR=1.90, 95%CI
      (1.74;2.07) for Periodontitis; OR=1.18, 95%CI (1.09;1.27) for dental caries;
      OR=1.84, 95%CI (1.64;2.07) for peri-implant pathology]. Attributable fractions
      estimated a potential reduction of 12.2% of Periodontitis, and 4.3% of dental
      caries cases if the exposure to systemic conditions was prevented; while the
      prevention of exposure to smoking alone would result in a potential reduction of
      37%, 7%, and 39% of Periodontitis, dental caries, and peri-implant pathology
      cases, respectively. CLINICAL SIGNIFICANCE: The present study describes an
      epidemiological approach to the distribution and determinants of the three
      principal chronical oral diseases. The association of systemic conditions and
      smoking habits with oral disease prevalence highlight the importance of a narrow
      monitoring system. CONCLUSIONS: The present study reported a high prevalence for
      oral disease and a potential association of a systemic compromised status and
      smoking habits with the three chronical oral diseases.

PMID- 28750779
TI  - Proinflammatory Dual Receptor T Cells in Chronic Graft-versus-Host Disease.
AB  - Defective post-transplantation thymopoiesis is associated with chronic graft
      versus-host disease (GVHD), a multiorgan pathology affecting up to 80% of
      patients after allogeneic hematopoietic stem cell transplantation (HSCT).
      Previous work demonstrated that the subset of T cells expressing 2 T cell
      receptors (TCRs) is predisposed to alloreactivity, driving selective and
      disproportionate activity in acute GVHD in both mouse models and HSCT patients.
      Here we investigate a potential role for this pathogenic T cell subset in chronic
      GVHD (cGVHD). HSCT patients with cGVHD demonstrated increased numbers of dual TCR
      cells in circulation. These dual receptor cells had an activated phenotype,
      indicating an active role in cGVHD. Notably, single-cell RNA sequencing
      identified the increased dual TCR cells in cGVHD as predominantly expressing
      Tbet, indicative of a proinflammatory phenotype. These results identify dual TCR
      cells as specific mediators of pathogenic inflammation underlying cGVHD and
      highlight Tbet-driven T cell function as a potential pathway for potential
      therapeutic targeting.

PMID- 28750778
TI  - Delayed photo-activation and addition of thio-urethane: Impact on polymerization
      kinetics and stress of dual-cured resin cements.
AB  - OBJECTIVE: 1) to determine the moment during the redox polymerization reaction of
      dual cure cements at which to photo-activate the material in order to reduce the
      polymerization stress, and 2) to evaluate possible synergistic effects between
      adding chain transfer agents and delayed photo-activation. METHODS: The two
      pastes of an experimental dual-cure material were mixed, and the polymerization
      kinetics of the redox phase was followed. The moment when the material reached
      its maximum rate of redox polymerization (MRRP) of cement was determined. The
      degree of conversion (DC) and maximum rates of polymerization (Rpmax) were
      assessed for materials where: the photoactivation immediately followed material
      mixing, at MRRP, 1min before and 1min after MRRP. Thio-urethane (TU) additives
      were synthesized and added to the cement (20% wt), which was then cured under the
      same conditions. The polymerization kinetics was evaluated for both cements photo
      activated immediately or at MRRP, followed by measurements of polymerization
      stress, flexural strength (FS) and elastic modulus (EM). Knoop hardness was
      measured before and after ethanol storage. RESULTS: Photo-activating the cement
      at or after MRRP reduced the Rpmax and the polymerization stress. Addition of TU
      promoted additional and more significant reduction, while not affecting the
      Rpmax. Greater hardness loss was observed for cements with TU, but the final
      hardness was similar for all experimental conditions. Addition of TU slightly
      reduced the EM and did not affect the FS. CONCLUSION: Delayed photo-activation
      and addition of TU significantly reduce the polymerization stress of dual-cured
      cements.

PMID- 28750780
TI  - Influence of psychological variables in morbidly obese patients undergoing
      bariatric surgery after 24 months of evolution.
AB  - BACKGROUND: Bariatric surgery is considered a more effective means of achieving
      weight loss than non-surgical options in morbid obesity. Rates of failure or
      relapse range from 20 to 30%. The study aims to analyse the influence of
      psychological variables (self-esteem, social support, coping strategies and
      personality) in the maintenance of weight loss after bariatric surgery. METHODS:
      A cohort study was conducted involving 64 patients undergoing bariatric surgery
      for 24 months. At the end of the follow-up period, patients were divided into
      2sub-cohorts classified as successes or failures. Success or favorable
      development was considered when the value of percent excess weight loss was 50 or
      higher. RESULTS: No statistically significant differences were observed between
      the 2groups in any variable studied. All patients had high self-esteem (87,3
      those who failed and 88,1 those who are successful) and social support (90,2 and
      90,9). Patients who succeed presented higher scores for cognitive restructuring
      (57,1) and were more introverted (47,1), while those who failed scored more
      highly in desiderative thinking (65,7) and were more prone to aggression (50,7)
      and neuroticism (51,7). CONCLUSIONS: High self-esteem and social support does not
      guarantee successful treatment. The groups differed in how they coped with
      obesity but the data obtained do not justify the weight evolution. In the absence
      of psychopathology, personality trait variability between patients is
      insufficient to predict the results.

PMID- 28750781
TI  - Corrigendum to "The thermophilic (55 degrees C) microaerobic pretreatment of corn
      straw for anaerobic digestion" [Bioresour. Technol. 175 (2015) 203-208].

PMID- 28750782
TI  - Aspiration Pneumonia in the Dog: A Review.
AB  - OBJECTIVE: To review the human and veterinary literature pertaining to aspiration
      pneumonitis and pneumonia. MATERIAL AND METHODS: Data sources included scientific
      reviews and original research publications from the human and veterinary
      literature. All reviews and studies that added to the understanding of aspiration
      pneumonia were included. RESULTS: Compared to human medicine, aspiration
      pneumonia can be difficult to diagnose in the canine patient and is often a
      diagnosis of presumption. Multiple risk factors exist increasing the likelihood
      of aspiration pneumonia and a thorough understanding of these can aid in
      prevention. Treatment recommendations center primarily on supportive care, oxygen
      therapy and antibiotic administration. CLINCIAL SIGNIFICANCE: Aspiration
      pneumonia is a common finding in the canine patient and a thorough understanding
      of the disease will lead to better treatment outcomes. Further studies on
      treatment and prevention in veterinary medicine are warranted.

PMID- 28750783
TI  - Effects of Cabergoline on Thyroid Hormones and Semen Quality of Dog.
AB  - In this study, the concentration of prolactin, FT4, and semen quality were
      investigated in 5 clinically healthy fertile mixed-breed dogs (1-3 years old)
      treated with cabergoline (5MUg/kg) during 9 weeks. Semen analysis was performed
      for volume, live or dead, concentration, and motility factors every week. The
      results indicated that cabergoline administration caused a minor but significant
      reduction of the mean prolactin concentration (P < .05) and did not affect the
      secretion of FT4 (P > .05). Further, there was not a significant effect of
      cabergoline on semen quality, statistically. We could not find any relationship
      between prolactin and FT4 concentration and changes in semen characteristics.

PMID- 28750784
TI  - The Clinical Follow-Up of Estradiol Benzoate Priming During Induction of Estrus
      With Cabergoline in Dogs.
AB  - Induction of estrus is used to improve reproductive efficiency of female dogs. In
      this study, 11 adult healthy female dogs were selected at anestrus stage. The
      dogs were assigned to treatment (6 dogs) and control groups (5 dogs). Single dose
      of estradiol benzoate was injected in treatment group at day 0 (0.01mg/kg, IM).
      Dogs in both groups received cabergoline (5MUg/kg orally) from day 7 to the onset
      of proestrus. Vaginal cytology and blood samples were taken twice a week during
      study. Average time to the onset of proestrus was 10.33 +/- 4.2 and 15 +/- 7.5
      days in the treatment and control groups, respectively (P = .08). The differences
      in time to the onset of estrus phase in the treatment group (14.67 +/- 5.9 days)
      and control group (18.67 +/- 10.8 days) were significant (P < .05). The average
      length of proestrus phase in treatment and control groups was 5.33 +/- 2.2 and 8
      +/- 4.6 days, respectively and their differences were significant (P < .05).
      Average length of estrus phase in treated dogs with estradiol benzoate was 8.57
      +/- 3.5 days but it was 8 +/- 4.6 days in control group (P > .05). Administration
      of cabergoline caused significant decrease of prolactin concentration in both
      groups (P < .01). The difference in serum prolactin concentration between
      treatment and control was not significant. The effect of cabergoline on serum
      prolactin concentration was not affected by administration of estradiol benzoate
      in treatment group (P > .05). As a result, administration of estradiol benzoate 1
      week before cabergoline improved induction and synchronization of estrus in dogs.

PMID- 28750785
TI  - Cerebellar Cortical Abiotrophy in Young Labrador-Retrievers.
AB  - Cerebellar abiotrophy is a hereditary degenerative disorder of the central
      nervous system in humans and animals. Four male and one female Labrador-retriever
      pups were presented with clinical signs of head swaying with intention tremor,
      loss of target oriented movement, wide base stance, forelimb hypermetria, and
      hindlimb ataxia leading to falling off during ambulation. On histopathologic
      examination of cerebellum, cerebellar cortical abiotrophy was confirmed with
      extensive loss of Purkinje cells, diminution of granular layer, relative
      thickening and foliar gliosis in white matter. This is the first reported case of
      cerebellar abiotrophy in Labrador-retriever to our knowledge.

PMID- 28750786
TI  - Proteomic Analysis of Synovial Fluid Obtained From a Dog Diagnosed With
      Idiopathic Immune-Mediated Polyarthritis.
AB  - This case study is to report the proteins detected by proteomic analysis of
      synovial fluid from a dog diagnosed with idiopathic immune-mediated
      polyarthritis, and to compare it with healthy dogs. Synovial fluid was collected
      via arthrocentesis from a dog diagnosed with immune-mediated polyarthritis.
      Protein precipitation was performed on the synovial fluid, followed by
      isoelectric focusing and 2-dimensional gel electrophoresis. The spots on the 2
      dimensional gels were analyzed using MALDI-TOF/MS. The results were then analyzed
      against the MASCOT database. The results from the proteomic analysis revealed an
      abundance of several types of immunoglobulins together with the presence of
      complement C4b-binding protein alpha chain. Actin and keratin were also among the
      proteins detected. Proteomic studies, facilitate a better understanding of the
      different levels of proteins expressed during disease activity. Potential disease
      biomarkers can aid in the diagnosis of disease, as well as help in monitoring
      treatment efficacy and providing prognosis for the patient.

PMID- 28750787
TI  - High-Dose Filgrastim Treatment of Nonregenerative Pancytopenia Associated With
      Chronic Canine Ehrlichiosis.
AB  - OBJECTIVE: To report the management and outcome of a dog with canine monocytic
      ehrlichiosis and nonregenerative pancytopenia, with high doses of filgrastim.
      CASE DESCRIPTION: An 8-year-old male, mixed-breed dog, weighing 5.6kg, presented
      with a 1-month history of hyporexia, adynamia, and a weight loss of approximately
      1kg. The general condition of the dog was observed to be poor as follows:
      lethargy, tachycardia, marked pallor of the mucous membranes, petechiae on the
      abdomen, hepatosplenomegaly, and cervical lymphadenopathy. A complete blood count
      analysis revealed severe leukopenia, thrombocytopenia, and anemia. A direct
      immunofluorescence assay using anti-Ehrlichia canis-immunoglobin G (1:400)
      yielded positive result. The dog was diagnosed with nonregenerative pancytopenia
      associated with canine monocytic ehrlichiosis. The dog presented poor prognostic
      signs (neutropenia, thrombocytopenia, and severe anemia). The dog was treated
      with antibiotics and a short course of high-dose filgrastim (50ug/kg, SC, q 48h
      for 4 days) to stimulate bone marrow response, prednisone to decrease peripheral
      platelet destruction, and an iron supplement to compensate for the iron
      deficiency in the bone deposits. Although temporary side effects associated with
      filgrastim use, such as bone pain, bleeding, and the worsening of
      thrombocytopenia, were observed, the treatment improved the clinical course and
      the cell counts in less than a month. CLINICAL RELEVANCE: The treatment protocol
      used in this case might be an alternative for treating cases of severe
      myelosuppression. This treatment plan can substantially change the clinical
      course of the disease for the better, compared to conventional treatment.

PMID- 28750788
TI  - Autologous Platelet Concentrates as Treatment for Avascular Necrosis of Femoral
      Head in a Dog.
AB  - Avascular necrosis of the femoral head is a developmental disturbance that
      generally affects young dogs of small breeds and produces ischemic necrosis of
      the femoral head resulting in an incongruous and malformed joint. The most common
      treatment is the excisional arthroplasty of the head and femoral neck. The aim of
      this study is to describe the treatment of avascular necrosis in a Yorkshire dog
      using intra-articular injections of autologous platelet concentrate. Evaluations
      were made at 0, 15, 30, 60, and 120 days of treatment, describing the following
      parameters: clinical gait analysis, perimetry, goniometry, and radiographic
      evaluations. The results obtained in this case suggest that the autologous
      platelet concentrate may be an alternative for the treatment of avascular
      necrosis of the femoral head in dogs.

PMID- 28750789
TI  - Acute Hypoxemic Respiratory Failure With Hemoptysis in a Dog Exposed to Copper
      Sulfate Powder.
AB  - A 2-year-old male mongrel dog was presented because of the onset of dry cough.
      About 16 hours before, the dog had been exposed to the pesticide that the owner
      was spraying in the vineyard. Approximately 3 hours later an acute respiratory
      failure, with a rapid evolution, began. Hemoptysis and regenerative normocytic
      normochromic anemia arose within hours, and a pulmonary hemorrhage was diagnosed.
      Pulmonary hemorrhage fast led to pneumonia, as evidenced by the serial CXR
      findings and the developing of leukocytosis. The hypothesis that we believe more
      likely is that the dog inhaled an amount of copper sulfate powder enough to
      determine respiratory tree damage, extending from the trachea to the pulmonary
      alveoli. Oxygen supplementation, antibiotics, antioxidant, and gastroprotective
      medications had been administered. After 4 days of hospitalization the dog was
      discharged. After a follow-up of more than 2 years later, the dog is still alive
      and in good health. To the authors knowledge no evidences of acute pulmonary
      involvement after copper sulfate inhalation exist in any species. This report is
      a contribution to the knowledge of copper poisoning, scarcely mentioned both in
      human and veterinary literature, and which has never been described in companion
      animals.

PMID- 28750790
TI  - Evaluation of the Effect of Mesotherapy in the Management of Osteoarthritis
      Related Pain in a Police Working Dog Using the Canine Brief Pain Inventory.
AB  - CASE DESCRIPTON: A 9-year-old, 33.4kg (73.63Lb) male entire drug detection
      Labrador Retriever Dog was presented with an history of constant lameness from
      the right thoracic limb, aggravated with exercise and work. CLINICAL FIDINGS:
      Clinical examination revealed mild signs of pain on the manipulation of the elbow
      joint, with reduced range of motion on the end feel of joint flexion and
      extension and crepitation. Radiographic examination of the right elbow joint
      revealed severe, chronic osteoarthritis, with osteophyte formation on the humeral
      epicondyles and articular margin of the distomedial humerus, with a narrowed
      joint space, and osteophytes on the proximal radius, proximomedial ulna, and
      anconeal process. TREATMENT AND OUTCOME: A solution comprised of a combination of
      lidocaine, thiocolchicoside, and piroxicam was prepared and applied around the
      right elbow joint. The animal was rested for 3 days and normal work load was
      introduced over a 5-day period. The CPBI was completed by the trainer before
      treatment (T0), 14 days (T1), 1 (T2), 2 (T3), 3 (T4), 4 (T5), 5 (T6), and 6 (T7)
      months after treatment. Following the mesotherapy session, pain score results
      consistently declined until the 3-month evaluation moment. At the 6-month follow
      up evaluation, values have risen to near baseline values. No side effects were
      recorded. CLINICAL RELEVANCE: Mesotherapy produced significant reduction of pain
      score results, as measure by the CBPI, and may be a promising treatment option
      for canine osteoarthritis-related pain. Further studies are required.

PMID- 28750791
TI  - Use of Nandrolone Decanoate in Treatment of Pure Red Cell Aplasia Secondary to
      Diclofenac Administration: A Case Report.
AB  - Pure red cell aplasia (PRCA) is a disorder that leads to a nonregenerative anemia
      that results from erythroid precursors failing to reach maturity in the bone
      marrow, whereas the numbers of mature myeloid and megakaryocytic cells remain
      normal. PRCA can be induced by autoimmune processes, infections, drugs, toxins,
      and radiation, and is diagnosed by a bone marrow cytology examination after
      excluding the most common causes of nonregenerative anemia. Immunosuppressive
      therapies are used to treat PRCA, and usually involve the use of glucocorticoids,
      cyclosporin, or azathioprine. Alternatively, although little studied in
      veterinary medicine, drugs which stimulate bone marrow (e.g., nandrolone
      decanoate) have been mentioned as possible therapeutic agents. A case of PRCA
      that presented at the Veterinary Teaching Hospital of the Faculty of Veterinary
      Medicine and Animal Science (UNESP)-Botucatu, Brazil showed a good therapeutic
      response to weekly administration of nandrolone decanoate. Therefore, it was
      concluded that bone marrow stimulants might improve the quality of life of PRCA
      patients, provided they are used with caution and under close clinical
      supervision.

PMID- 28750792
TI  - Heat Shock Proteins 70kDa, Eosinophil Cationic Protein, and Nitric Oxide During
      Chronic Superficial Keratitis in Dogs.
AB  - The objective of the study is to determine the levels of eosinophil cationic
      protein (ECP), heat shock proteins 70, and nitric oxide ions measured as nitrite
      ions (Griess reaction) in dogs with chronic superficial keratitis (CSK). The
      study was conducted on 24 dogs with CSK. Blood sera from the animals were tested
      for concentrations of heat shock proteins 70, ECP, and nitrite ions before
      treatment and again 5 weeks and 6 months after treatment. Dogs with CSK were
      treated for 6 months with various regimes involving the use of ophthalmic drops
      containing dexamethasone, dimethyl sulfoxide, and cyclosporine. The control group
      consisted of 16 clinically healthy German Shepherds. The results obtained
      indicated a significant (P <= 0.05) elevation in the concentrations of heat shock
      proteins 70 and nitrite ions in dogs with CSK in comparison to healthy dogs and
      dogs after 5 weeks of therapy. After 6 months of treatment, concentrations of
      heat shock proteins 70, ECP, and nitrite ions had fallen below pretreatment
      values. Significant correlations were found between concentrations of heat shock
      proteins 70, ECP, and nitrite ions in healthy animals and animals with CSK. The
      elevated concentrations of heat shock proteins 70, ECP, and nitrite ions in dogs
      with CSK may indicate that the disease was both localized and systemic. The
      significant correlation between levels of heat shock proteins 70 and nitrite ions
      suggests that these parameters may be used as indirect indicators of CSK.

PMID- 28750793
TI  - Ocean acidification hampers sperm-egg collisions, gamete fusion, and generation
      of Ca2+ oscillations of a broadcast spawning bivalve, Tegillarca granosa.
AB  - Although the effect of ocean acidification on fertilization success of marine
      organisms is increasingly well documented, the underlying mechanisms are not
      completely understood. The fertilization success of broadcast spawning
      invertebrates depends on successful sperm-egg collisions, gamete fusion, and
      standard generation of Ca2+ oscillations. Therefore, the realistic effects of
      future ocean pCO2 levels on these specific aspects of fertilization of Tegillarca
      granosa were investigated in the present study through sperm velocity trials,
      fertilization kinetics model analysis, and intracellular Ca2+ assays,
      respectively. Results obtained indicated that ocean acidification significantly
      reduced the fertilization success of T. granosa, which could be accountable by
      (i) decreased sperm velocity hence reducing the probability for sperm-egg
      collisions; (ii) lowered probability of gamete fusion for each gamete collision
      event; and (iii) disrupted intracellular Ca2+ oscillations.

PMID- 28750794
TI  - Mediastinal injury is the strongest predictor of mortality in mounted blast
      amongst UK deployed forces.
AB  - BACKGROUND: Blast injury has been the most common cause of morbidity and
      mortality encountered by UK forces during recent conflicts. Injuries sustained by
      blast are categorised by the injuring component of the explosion and depend upon
      physical surroundings. Previous work has established that head injuries and intra
      cavity haemorrhage are the major causes of death following exposure to under body
      (mounted) blast but has yet to explore the precise nature of these torso injuries
      nor the effect of particular injuries upon survival. This study examines the
      patterns of torso injury within the mounted blast environment in order to
      understand the effect of these injuries upon survivability. METHODS: This
      retrospective study examined the UK Joint Theatre Trauma Registry to determine
      precise injury patterns of mounted blast casualties within a 13year period of UK
      military deployments. Survival rates of individual injuries were compared and a
      multivariable logistic regression model was developed in order to assess the
      effect that each injury had upon likelihood of death. RESULTS: 426 mounted
      casualties were reviewed of whom 129 did not survive. Median NISS and ISS for non
      survivors was found to be 75. Torso injuries were significantly more common
      amongst non-survivors than survivors and high case fatality rates were associated
      with all haemorrhagic torso injuries. Multivariable analysis shows that
      mediastinal injuries have the largest odds ratio for mortality (20.4) followed by
      lung laceration and head injury. CONCLUSIONS: Non-compressible torso haemorrhage
      is associated with mortality amongst mounted blast. Of this group, mediastinal
      injury is the strongest predictor of death and could be considered as a surrogate
      marker of lethality. Future work to link blast loading characteristics with
      specific injury patterns will inform the design of mitigating strategies in order
      to improve survivability of underbody blast.

PMID- 28750795
TI  - Atrial fibrillation and patent foramen potentially share same atrial flow dynamic
      profile and thrombotic mechanism.

PMID- 28750796
TI  - The N-terminal extension of the P. falciparum GBP130 signal peptide is irrelevant
      for signal sequence function.
AB  - The malaria parasite P. falciparum exports a large number of proteins to its host
      cell, the mature human erythrocyte. Although the function of the majority of
      these proteins is not well understood, many exported proteins appear to play a
      role in modification of the erythrocyte following invasion. Protein export to the
      erythrocyte is a secretory process that begins with entry to the endoplasmic
      reticulum. For most exported proteins, this step is mediated by hydrophobic
      signal peptides found towards the N-terminal end of proteins. The signal peptides
      present on P. falciparum exported proteins often differ in length from those
      found in other systems, and generally contain a highly extended N-terminal
      region. Here we have investigated the function of these extended N-terminal
      regions, using the exported parasite protein GBP130 as a model. Surprisingly,
      several deletions of the extended N-terminal regions of the GBP130 signal peptide
      have no effect on the ability of the signal peptide to direct a fluorescent
      reporter to the secretory pathway. Addition of the same N-terminal extension to a
      canonical signal peptide does not affect transport of either soluble or membrane
      proteins to their correct respective subcellular localisations. Finally, we show
      that extended signal peptides are able to complement canonical signal peptides in
      driving protein traffic to the apicoplast of the parasite, and are also
      functional in a mammalian cell system. Our study is the first detailed analysis
      of an extended P. falciparum signal peptide and suggests that N-terminal
      extensions of exported Plasmodium falciparum proteins are not required for entry
      to the secretory system, and are likely to be involved in other, so far unknown,
      processes.

PMID- 28750797
TI  - Reliability of a multiplex PCR system for diagnosis of early and late prosthetic
      joint infections before and after broth enrichment.
AB  - Early microbiological diagnosis of prosthetic joint infection (PJI) is essential
      for successful antimicrobial treatment; however, culture has limited sensitivity,
      particularly in patients who had received antibiotic therapy, and the utility of
      molecular methods for diagnosing PJIs remains debated. We investigated the
      reliability of a multiplex PCR system for the microbiological diagnosis of early
      and late PJIs. Samples of periprosthetic tissues, synovial fluid, and prosthetic
      implants from 47 patients with early (n=13) or late (n=34) PJI were analyzed by
      conventional culture and with the multiplex-PCR Unyvero ITI(r) (U-ITI) cartridge
      system. Samples treated with dithiothreitol (DTT) and synovial fluids were spread
      directly on agar plates and inoculated into enrichment broths. The synovial
      fluids, DTT eluates and enrichment broths were processed according to the U-ITI
      protocol. When compared against culture as the reference method, U-ITI analysis
      of DTT eluates had a sensitivity of 34.2%; sensitivity of U-ITI analysis
      increased up to 81.6% when enrichment broths were analyzed. In particular,
      sensitivity was 44.4% for synovial fluids, and 41.7%, and 23.5% for DTT eluates
      from early and late infections, respectively. Sensitivity of analysis of
      enrichment broths was 83.3% for early infections, 82.3% for late infections and
      77.8% for synovial fluids. Our findings seem to suggest that, when coupled with
      the use of broth culture, U-ITI analysis may allow for more rapid microbial
      identification than biochemical methods, while no advantages in time to detect
      microbial growth were observed. Improvements, particularly in sensitivity, are
      needed to make it more suitable for diagnosis of early and late PJIs.

PMID- 28750798
TI  - Functional pectoralis minor myocutaneous flap transplantation for reconstruction
      of thumb opposition: An anatomic study with clinical applications.
AB  - OBJECTIVE: To develop a myocutaneous flap for reconstruction of thumb opposition
      function in patients with loss of the thenar muscles and skin. METHODS: An
      anatomic experiment on the dimensions of the pectoralis minor muscle and its
      neurovascular supply in 10 adult human cadavers was conducted to evaluate the
      feasibility of microsurgical transplantation using part of the muscle for thumb
      opposition reconstruction. Based on these results, we performed surgical thenar
      reconstruction with a pectoralis minor myocutaneous flap in seven patients (34.7
      +/- 9.8 years of age) from December 2007 to October 2010. RESULTS: The
      transferred muscle was reinnervated with the third lumbrical branch of the ulnar
      nerve. Six to twelve months after the surgery, follow-up assessment showed that
      all patients had recovered functional opposition of the carpometacarpal joint
      with survival of the skin and a muscle power of M4 to M5. CONCLUSION: Our results
      support the use of this new technique for thenar and opposition reconstruction in
      patients with severe loss of the thenar muscles and skin and damage to the median
      nerve and who wish to improve the appearance of the thenar eminence.

PMID- 28750799
TI  - Mouse Neuroblastoma CB1 Cannabinoid Receptor-Stimulated [35S]GTPgammaS Binding:
      Total and Antibody-Targeted Galpha Protein-Specific Scintillation Proximity
      Assays.
AB  - G protein-coupled receptors (GPCRs) are important regulators of cellular
      signaling functions and therefore are a major target for drug discovery. The CB1
      cannabinoid receptor is among the most highly expressed GPCRs in neurons, where
      it regulates many differentiated neuronal functions. One model system for
      studying the biochemistry of neuronal responses is the use of neuroblastoma cells
      originating from the C1300 tumor in the A/J mouse, including cloned cell lines
      NS20, N2A, N18TG2, N4TG1, and N1E-115, and various immortalized hybrids of
      neurons with N18TG2 cells. GPCR signal transduction is mediated through
      interaction with multiple types and subtypes of G proteins that transduce the
      receptor stimulus to effectors. The [35S]GTPgammaS assay provides a valuable
      pharmacological method to evaluate efficacy and potency in the first step in GPCR
      signaling. Here, we present detailed protocols for the [35S]GTPgammaS-binding
      assay to measure the total G protein binding and the antibody-targeted
      scintillation proximity assay to measure specific Galpha proteins in
      neuroblastoma cell membrane preparations. This chapter presents step-by-step
      methods from cell culture, membrane preparation, assay procedures, and data
      analysis.

PMID- 28750800
TI  - Lipidomics: A Corrective Lens for Enzyme Myopia.
AB  - Classifications and characterizations of specific proteins, such as enzymes, not
      only allow us to understand biosynthetic and metabolic pathways but they also
      help to drive our understanding of protein structure and function. How those
      characterizations are evaluated, however, may change our interpretations and lead
      us into broader and novel directions in research. Here, we will make the argument
      that using lipidomics as a tool for characterizing enzymatic function over more
      traditional toolkit options allows for these types of revelations. Using
      lipidomics techniques on specific brain regions with a series of enzyme knockout
      and disease models, we have generated a novel set of analyses from which to view
      protein function. Through these data, we have demonstrated that NAPE-PLD, MAG
      lipase, and FAAH all have broader roles throughout the brain than previously
      thought. Much like the data on how the extinction of specific species within an
      ecosystem has unpredicted outcomes, so too does the elimination of these enzymes
      affect the brain lipidome. From a purely biochemical standpoint, it is a
      fascinating story of how one change in a system can have exponential effects;
      however, from a drug-target standpoint, it may prove to be a cautionary tale.

PMID- 28750801
TI  - Functional Analysis of Mitochondrial CB1 Cannabinoid Receptors (mtCB1) in the
      Brain.
AB  - Recent evidence indicates that, besides its canonical localization at cell plasma
      membranes, the type-1 cannabinoid receptor, CB1 is functionally present at brain
      and muscle mitochondrial membranes (mtCB1). Through mtCB1 receptors, cannabinoids
      can directly regulate intramitochondrial signaling and respiration. This new and
      surprising discovery paves the way to new potential fields of research, dealing
      with the direct impact of G protein-coupled receptors on bioenergetic processes
      and its functional implications. In this chapter, we summarize some key
      experimental approaches established in our laboratories to identify anatomical,
      biochemical, and functional features of mtCB1 receptors in the brain. In
      particular, we describe the procedures to obtain reliable and controlled
      detection of mtCB1 receptors by immunogold electromicroscopy and by
      immunoblotting methods. Then, we address the study of direct cannabinoid effects
      on the electron transport system and oxidative phosphorylation. Finally, we
      present a functional example of the impact of mtCB1 receptors on mitochondrial
      mobility in cultured neurons. Considering the youth of the field, these
      methodological approaches will very likely be improved and refined in the future,
      but this chapter aims at presenting the methods that are currently used and, in
      particular, at underlining the need of rigorous controls to obtain reliable
      results. We hope that this chapter might help scientists becoming interested in
      this new and exciting field of research.

PMID- 28750802
TI  - Modeling Neurodegenerative Disorders for Developing Cannabinoid-Based
      Neuroprotective Therapies.
AB  - The increase in lifespan during the last 50 years, mainly in developed countries,
      has originated a progressive elevation in the incidence of chronic
      neurodegenerative disorders, for which aging is the key risk factor. This fact
      will definitively become the major biomedical challenge during the present
      century, in part because the expectation of a persisting elevation in the
      population older than 65 years over the whole population and, on the other hand,
      because the current lack of efficacious therapies to control these disorders
      despite years of intense research. This chapter will address this question and
      will stress the urgency of developing better neuroprotective and neurorepair
      strategies that may delay/arrest the progression of these disorders, reviewing
      the major needs to solve the causes proposed for the permanent failures
      experienced in recent years, e.g., to develop multitarget strategies, to use more
      predictive experimental models, and to identify early disease biomarkers. This
      chapter will propose the cannabinoids and their classic (e.g., endocannabinoid
      receptors and enzymes) and nonclassic (e.g., peroxisome proliferator-activated
      receptors, transcription factors) targets as a useful strategy for developing
      novel therapies for these disorders, based on their broad-spectrum
      neuroprotective profile, their activity as an endogenous protective system, the
      location of the endocannabinoid targets in cell substrates critical for neuronal
      survival, and their ability to serve for preservation and rescue, but also for
      repair and/or replacement, of neurons and glial cells against cytotoxic insults.

PMID- 28750803
TI  - Metabolic Profiling of CB1 Neutral Antagonists.
AB  - PIMSR is among the first neutral antagonists for the CB1R and was demonstrated
      pharmacologically to bind to the CB1R, yet not alter calcium flux. It was further
      shown computationally to be able to stabilize both the active and inactive states
      of CB1R revealing the molecular interactions that mechanistically afford the
      property of neutral antagonism. PIMSR shows dramatic positive effects in reducing
      weight, food intake, and adiposity as well as in improving glycemic control and
      lipid homeostasis in high-fat diet-induced obese mice, but also shows increased
      ALT and liver weight as markers of liver injury with chronic administration.
      Further, in a separate study, 3-day administration of PIMSR in C57BL/6J mice,
      hepatic steatosis from an acute administration of high of ethanol was
      significantly reduced. Also, it partially prevented alcohol-induced increases in
      ALT, AST, and LDH. The differences in ALT levels in obese and nonobese mice under
      different test paradigms are unlikely to be due to neutral antagonism itself
      since other neutral antagonists (AM6545) do not exhibit liver injury. The brain
      levels of low micromolar would support significant brain CB1 receptor occupancy
      (re: Ki=17nM), thus potentially including both CNS and peripheral influences on
      the observed weight loss. Overall, these studies suggest that marked improvements
      in aspects of metabolic disease and alcoholic steatosis can be realized with CB1R
      neutral antagonists and hence warrants the exploration of further members of this
      class of cannabinoid ligands.

PMID- 28750804
TI  - Ligand-Assisted Protein Structure (LAPS): An Experimental Paradigm for
      Characterizing Cannabinoid-Receptor Ligand-Binding Domains.
AB  - Detailed characterization of the ligand-binding motifs and structure-function
      correlates of the principal GPCRs of the endocannabinoid-signaling system, the
      cannabinoid 1 (CB1R) and cannabinoid 2 (CB2R) receptors, is essential to inform
      the rational design of drugs that modulate CB1R- and CB2R-dependent biosignaling
      for therapeutic gain. We discuss herein an experimental paradigm termed "ligand
      assisted protein structure" (LAPS) that affords a means of characterizing, at the
      amino acid level, CB1R and CB2R structural features key to ligand engagement and
      receptor-dependent information transmission. For this purpose, LAPS integrates
      three key disciplines and methodologies: (a) medicinal chemistry: design and
      synthesis of high-affinity, pharmacologically active probes as reporters capable
      of reacting irreversibly with particular amino acids at (or in the immediate
      vicinity of) the ligand-binding domain of the functionally active receptor; (b)
      molecular and cellular biology: introduction of discrete, conservative point
      mutations into the target GPCR and determination of their effect on probe binding
      and pharmacological activity; (c) analytical chemistry: identification of the
      site(s) of probe-GPCR interaction through focused, bottom-up, amino acid-level
      proteomic identification of the probe-receptor complex using liquid
      chromatography tandem mass spectrometry. Subsequent in silico methods including
      ligand docking and computational modeling provide supplementary data on the probe
      receptor interaction as defined by LAPS. Examples of LAPS as applied to human
      CB2R orthosteric binding site characterization for a biarylpyrazole
      antagonist/inverse agonist and a classical cannabinoid agonist belonging to
      distinct chemical classes of cannabinergic compounds are given as paradigms for
      further application of this methodology to other therapeutic protein targets.
      LAPS is well positioned to complement other experimental and in silico methods in
      contemporary structural biology such as X-ray crystallography.

PMID- 28750805
TI  - Protocols and Good Operating Practices in the Study of Cannabinoid Receptors.
AB  - With the approach of the 30th year since the pioneering discovery of a
      cannabinoid receptor in rat brain (Devane et al., 1988), the field of cannabinoid
      pharmacology and physiology has impacted human physiology at multiple levels. The
      development of highly specific and potent orthosteric ligands, as well as the
      blossoming field of allosteric ligand development, has placed the endocannabinoid
      system in the forefront as a modulator of a multitude of physiologic processes.
      Reproducibility among laboratories is especially important due to the development
      of novel tools to investigate the role(s) of the endocannabinoid system in human
      physiology, and to clarify the roles for medicinal marijuana. Any definitive role
      in normal, or diseased states, must be satisfied through the demonstration of a
      specific receptor-mediated event. This chapter provides working protocols for the
      study of cannabinoid receptor-ligand binding, as well as immediate and downstream
      G protein-dependent signaling assays to assess receptor function.

PMID- 28750806
TI  - New Methods for the Synthesis of Cannabidiol Derivatives.
AB  - Cannabidiol (CBD) is one of the most abundant components isolated from Cannabis
      sativa. However, CBD is a nonpsychotropic phytocannabinoid. In the last decade,
      there has been a growing interest in its therapeutic effects. This is why this
      natural product represents a lead structure for the development of new
      cannabinoid compounds. Even though chemistry of CBD has been explored for more
      than 30 years, the synthesis of only a few derivatives has been described. This
      chapter first reviews the synthetic methods for the preparation of CBD and
      derivatives. Then, it describes procedures for the synthesis of N-heterocyclic
      derivatives of CBD with, in particular, the preparation and structural
      characterization of 5-alkyl-2-(1H-pyrazol-3-yl)benzene-1,3-diol.

PMID- 28750807
TI  - Approaches to Assess Biased Signaling at the CB1R Receptor.
AB  - G protein-coupled receptors, such as the cannabinoid type 1 receptor (CB1R), have
      been shown to interact with multiple binding partners to transmit signals. In
      both transfected cell systems and in endogenously expressing cell lines, CB1R
      signaling has been described as multifaceted. The question remains as to how this
      highly widely expressed receptor signals in a given cell at a given time in vivo.
      The concept of functional selectivity, or biased agonism, describes the ability
      of an agonist to engage the receptor in a manner that preferentially engages
      certain signaling interactions (e.g., G proteins) over others (e.g., beta
      arrestins), presumably by stabilizing certain receptor conformations. There is
      growing interest in using such properties of ligands to direct signaling
      downstream of CB1R toward desirable therapeutic outcomes and to avoid adverse
      side effects. While it is not currently clear what pathways should be engaged and
      which should be avoided, the development of biased agonist tool compounds will
      aid in answering these questions. In this chapter, we discuss the approaches and
      caveats to assessing biased agonism at the CB1R.

PMID- 28750808
TI  - Design and Synthesis of Cannabinoid 1 Receptor (CB1R) Allosteric Modulators: Drug
      Discovery Applications.
AB  - Also expressed in various peripheral tissues, the type-1 cannabinoid receptor
      (CB1R) is the predominant G protein-coupled receptor (GPCR) in brain, where it is
      responsible for retrograde control of neurotransmitter release. Cellular
      signaling mediated by CB1R is involved in numerous physiological processes, and
      pharmacological CB1R modulation is considered a tenable therapeutic approach for
      diseases ranging from substance-use disorders and glaucoma to metabolic syndrome.
      Despite the design and synthesis of a variety of bioactive small molecules
      targeted to the CB1R orthosteric ligand-binding site, the potential of CB1R as a
      therapeutic GPCR has been largely unrealized due to adverse events associated
      with typical orthosteric CB1R agonists and antagonists/inverse agonists.
      Modulation of CB1R-mediated signal transmission by targeting alternative
      allosteric ligand-binding site(s) on the receptor has garnered interest as a
      potentially safer and more effective therapeutic modality. This chapter
      highlights the design and synthesis of novel, pharmacologically active CB1R
      allosteric modulators and emphasizes how their molecular properties and the
      positive and negative allosteric control they exert can lead to improved CB1R
      targeted pharmacotherapeutics, as well as designer covalent probes that can be
      used to map CB1R allosteric binding domains and inform structure-based drug
      design.

PMID- 28750810
TI  - Purification of Functional CB1 and Analysis by Site-Directed Fluorescence
      Labeling Methods.
AB  - The human cannabinoid receptor, CB1, has been difficult to purify in a functional
      form, hampering structural and biophysical studies. Here, we present our
      approaches for obtaining pure, detergent solubilized, functional CB1. We also
      discuss our site-directed fluorescence labeling (SDFL) methods for identifying
      different structural changes that CB1 can undergo upon binding different
      cannabinoid ligands. To identify optimal CB1 constructs for these studies (those
      with the best expression levels, solubility in detergent and function), we first
      screened various CB1-green fluorescent protein chimeras in a mammalian expression
      system. Once identified, we then tagged the best candidates with the 1D4 epitope
      (the C-terminus of rhodopsin) and purified them using a single-step
      immunoaffinity process. The resulting, highly pure proteins retain their ability
      to activate G-protein, and are ~85% functional, as assessed by radioligand
      binding studies. The SDFL studies involve introducing single cysteine residues at
      key places in the receptor, then labeling them with a small fluorophore, bimane.
      The spectral properties of the bimane probe are then monitored before and after
      addition of cannabinoid ligands. Changes in fluorescence of the attached probe
      indicate regions of the receptor undergoing conformational changes upon ligand
      binding. Together, these approaches set the stage for a deeper understanding of
      the structure and function of CB1. Access to pure, functional CB1 makes
      subsequent structural studies possible (such as crystallography and single
      particle EM analysis), and the SDFL studies enable a better structural and
      mechanistic understanding of this key receptor and the dynamic changes it
      undergoes during activation and attenuation.

PMID- 28750809
TI  - Assessing Allosteric Modulation of CB1 at the Receptor and Cellular Levels.
AB  - The cannabinoid CB1 receptor is abundant in the central nervous system and
      regulates neuronal transmission and other key physiological processes including
      those leading to pain, inflammation, memory, and feeding behavior. CB1 is
      activated by the endogenous ligands, arachidonoyl ethanolamine and 2-arachidonoyl
      glycerol, by various synthetic ligands (e.g., CP55940), and by Delta9
      tetrahydrocannabinol, the psychoactive component of Cannabis sativa. These CB1
      ligands are orthosteric and transduce downstream signals by binding CB1 and
      primarily inducing Gi coupling, but Gs and beta-arrestin coupling are also
      possible. Recently, allosteric modulators for CB1 were discovered that bind to
      topographically distinct sites and can noncompetitively impact the potency and
      efficacy of orthosteric compounds. These offer the exciting potential for
      mechanistic analyses and for developing therapeutics. Yet, it is critical to
      elucidate whether a compound is a positive allosteric modulator or a negative
      allosteric modulator of orthosteric ligand-induced CB1 profiles to understand
      pathway specificity and ameliorate diseases. In this chapter, we present
      equilibrium and kinetic binding analysis to reveal the impact of allosteric
      modulators on CB1. Also described are activities consistent with CB1 activation
      (or inactivation) and include cellular internalization of CB1 and downstream
      signaling patterns. Since many CB1 allosteric modulators do not enhance G protein
      coupling, it is critical to distinguish CB1 activation and biased signaling
      patterns via beta-arrestin from CB1 inactivation. These strategies can illuminate
      pathway specificity and are valuable for the fine-tuning of CB1 function.

PMID- 28750811
TI  - Mass Spectrometry Analysis of Human CB2 Cannabinoid Receptor and Its Associated
      Proteins.
AB  - Studying the assemblies and dynamics of the complex formed by cannabinoid
      receptors and their associated proteins is important for understanding the
      molecular basis for the functions of these receptors. In the absence of the
      crystal structures of these macromolecular complexes, mass spectrometry is a
      sensitive technique that can be used to study cannabinoid receptors and their
      associated proteins. In this chapter, three aspects of the work are presented:
      (1) mass spectrometry analysis of the primary sequence of the human CB2
      cannabinoid receptor after affinity chromatography purification of the receptor
      proteins, (2) functional proteomic analysis of CB2-associated proteins
      coimmunoprecipitated with CB2, and (3) chemical cross-linking and mass
      spectrometry analysis of CB2-G protein complex. The mass spectrometry approaches,
      in combination with mutagenesis and molecular modeling techniques, have been
      successfully used for studying the CB2-G protein complex. Similar approaches can
      also be applied for studying other G protein-coupled receptors in general.

PMID- 28750812
TI  - Expression and NMR Structural Studies of Isotopically Labeled Cannabinoid
      Receptor Type II.
AB  - Cannabinoid receptor type II (CB2) is an integral membrane protein with seven
      transmembrane helices that belongs to the large superfamily of rhodopsin-like G
      protein-coupled receptors. The CB2 is a part of the endocannabinoid system that
      plays a vital role in regulation of immune response, inflammation, pain, and
      other metabolic processes. Information about the structure and function of CB2 in
      cell membranes is essential for development of specific pharmaceuticals that
      target CB2 signaling. Methodology for recombinant expression, stable isotope
      labeling, purification, reconstitution into liposomes, and NMR characterization
      of functionally active CB2 is presented. Uniformly 13C-, 15N-labeled CB2 protein
      is expressed by fermentation of Escherichia coli in a medium of defined
      composition under controlled aeration, pH, and temperature and purified by tandem
      affinity chromatography. The receptor reconstituted into lipid bilayers is
      suitable for structural studies by solid-state NMR spectroscopy.

PMID- 28750814
TI  - Real-Time Measurement of Cannabinoid Receptor-Mediated cAMP Signaling.
AB  - Cannabinoid receptors, like other GPCRs, signal via a spectrum of related
      signaling pathways. Recently, monitoring GPCR-mediated cAMP signaling has become
      significantly easier with the development of genetically encoded, transfectable
      cAMP biosensors. Cell lines transfected with these biosensors can be monitored
      continuously, allowing the analysis of receptor-mediated signaling in
      unprecedented detail. Here, we describe a protocol for transfectable biosensors
      which report cellular cAMP concentrations by bioluminescence resonance energy
      transfer (BRET). This assay system has been utilized to elucidate the temporal
      nature of agonists and allosteric modulators of the cannabinoid receptor CB1. In
      particular, the CB1 allosteric modulator ORG27569 has been shown to modify
      receptor agonism in a time-dependent fashion; a characteristic which would not
      have been observed via traditional endpoint methods of detecting cAMP signaling.
      BRET cAMP biosensors are suitable for miniaturization and automation, and as such
      are valuable and cost-effective tools for moderate- to high-throughput
      experimental protocols.

PMID- 28750813
TI  - Methods for the Development of In Silico GPCR Models.
AB  - The Reggio group has constructed computer models of the inactive and G-protein
      activated states of the cannabinoid CB1 and CB2 receptors, as well as, several
      orphan receptors that recognize a subset of cannabinoid compounds, including
      GPR55 and GPR18. These models have been used to design ligands, mutations, and
      covalent labeling studies. The resultant second-generation models have been used
      to design ligands with improved affinity, efficacy, and subtype selectivity.
      Herein, we provide a guide for the development of GPCR models using the most
      recent orphan receptor studied in our lab, GPR3. GPR3 is an orphan receptor that
      belongs to the Class A family of G-protein-coupled receptors. It shares high
      sequence similarity with GPR6, GPR12, the lysophospholipid receptors, and the
      cannabinoid receptors. GPR3 is predominantly expressed in mammalian brain and
      oocytes and it is known as a Galphas-coupled receptor activated constitutively in
      cells. GPR3 represents a possible target for the treatment of different
      pathological conditions such as Alzheimer's disease, oocyte maturation, or
      neuropathic pain. However, the lack of potent and selective GPR3 ligands is
      delaying the exploitation of this promising therapeutic target. In this context,
      we aim to develop a homology model that helps us to elucidate the structural
      determinants governing ligand-receptor interactions at GPR3. In this chapter, we
      detail the methods and rationale behind the construction of the GPR3 active-and
      inactive-state models. These homology models will enable the rational design of
      novel ligands, which may serve as research tools for further understanding of the
      biological role of GPR3.

PMID- 28750816
TI  - Techniques for the Cellular and Subcellular Localization of Endocannabinoid
      Receptors and Enzymes in the Mammalian Brain.
AB  - This chapter attempts to piece together knowledge about new advanced microscopy
      techniques to study the neuroanatomical distribution of endocannabinoid receptors
      and enzymes at the level of cellular and subcellular structures and organelles in
      the brain. Techniques ranging from light to electron microscopy up to the new
      advanced LBM, PALM, and STORM super-resolution microscopy will be discussed in
      the context of their contribution to define the spatial distribution and
      organization of receptors and enzymes of the endocannabinoid system (ECS), and to
      better understand ECS brain functions.

PMID- 28750815
TI  - Molecular Dynamics Methodologies for Probing Cannabinoid Ligand/Receptor
      Interaction.
AB  - The cannabinoid type 1 and 2 G-protein-coupled receptors are currently important
      pharmacological targets with significant drug discovery potential. These
      receptors have been shown to display functional selectivity or biased agonism, a
      property currently thought to have substantial therapeutic potential. Although
      recent advances in crystallization techniques have provided a wealth of
      structural information about this important class of membrane-embedded proteins,
      these structures lack dynamical information. In order to fully understand the
      interplay of structure and function for this important class of proteins,
      complementary techniques that address the dynamical aspects of their function are
      required such as NMR as well as a variety of other spectroscopies. Complimentary
      to these experimental approaches is molecular dynamics, which has been
      effectively used to help unravel, at the atomic level, the dynamics of ligand
      binding and activation of these membrane-bound receptors. Here, we discuss and
      present several representative examples of the application of molecular dynamics
      simulations to the understanding of the signatures of ligand-binding and -biased
      signaling at the cannabinoid type 1 and 2 receptors.

PMID- 28750817
TI  - Endocannabinoid Transport Proteins: Discovery of Tools to Study Sterol Carrier
      Protein-2.
AB  - The endocannabinoid (eCB) neurotransmitter system regulates diverse neurological
      functions including stress and anxiety, pain, mood, and reward. Understanding the
      mechanisms underlying eCB regulation is critical for developing targeted
      pharmacotherapies to treat these and other neurologic disorders. Cellular studies
      suggest that the arachidonate eCBs, N-arachidonoylethanolamine (AEA) and 2
      arachidonoylglycerol (2-AG), are substrates for intracellular binding and
      transport proteins, and several candidate proteins have been identified. Initial
      evidence from our laboratory indicates that the lipid transport protein, sterol
      carrier protein 2 (SCP-2), binds to the eCBs and can regulate their cellular
      concentrations. Here, we present methods for evaluating SCP-2 binding of eCBs and
      their application to the discovery of the first inhibitor lead molecules. Using a
      fluorescent probe displacement assay, we found SCP-2 binds the eCBs, AEA
      (Ki=0.68+/-0.05MUM) and 2-AG (Ki=0.37+/-0.02MUM), with moderate affinity. A
      series of structurally diverse arachidonate analogues also bind SCP-2 with Ki
      values between 0.82 and 2.95MUM, suggesting a high degree of tolerance for
      arachidonic acid head group modifications in this region of the protein. We also
      report initial structure-activity relationships surrounding previously reported
      inhibitors of Aedis aegypti SCP-2, and the results of an in silico high
      throughput screen that identified structurally novel SCP-2 inhibitor leads. The
      methods and results reported here provide the basis for a robust probe discovery
      effort to fully elucidate the role of facilitated transport mediated by SCP-2 in
      eCB regulation and function.

PMID- 28750818
TI  - Preface.

PMID- 28750819
TI  - Surgery Versus Conventional Radiation Therapy for T1-2 N0 M0 Small-cell Lung
      Cancer: A Fair Comparison?

PMID- 28750821
TI  - Corrections.

PMID- 28750820
TI  - Low temperature plasma induces angiogenic growth factor via up-regulating hypoxia
      inducible factor 1alpha in human dermal fibroblasts.
AB  - Numerous studies on the application of low temperature plasma (LTP) have produced
      impressive results, including antimicrobial, antitumor, and wound healing
      effects. Although LTP research has branched out to include medical applications,
      the detailed effects and working mechanisms of LTP on wound healing have not been
      fully investigated. Here, we investigated the potential effect of inducing growth
      factor after exposure to LTP and demonstrated the increased expression of
      angiogenic growth factor mediated by LTP-induced HIF1alpha expression in primary
      cultured human dermal fibroblasts. In cell viability assays, fibroblast viability
      was reduced 6 h and 24 h after LTP treatment for only 5 min, and pre-treating
      with NAC, a ROS scavenger, prevented cell loss. Fibroblast migration
      significantly increased at 6 h and 24 h in scratch wound healing assays, the
      expression of cytokines significantly changed, and regulatory growth factors were
      induced at 6 h and 24 h after exposure to LTP in RT-PCR or ELISAs. Specifically,
      LTP treatment significantly induced the expression of HIF1alpha, an upstream
      regulator of angiogenesis. Pre-treatment with the inhibitor CAY10585 abolished
      HIF1alpha expression and prevented LTP-induced angiogenic growth factor
      production according to immunoblotting, immunocytochemistry, and ELISA results.
      Taken together, our results provide information on the molecular mechanism by
      which LTP application may promote angiogenesis and will aid in developing methods
      to improve wound healing.

PMID- 28750822
TI  - Linking cannabis use to depression and suicidal thoughts and behaviours.

PMID- 28750823
TI  - Major depressive disorder, suicidal thoughts and behaviours, and cannabis
      involvement in discordant twins: a retrospective cohort study.
AB  - BACKGROUND: Early and frequent cannabis use are associated with an increased
      likelihood of major depressive disorder (MDD) as well as suicidal thoughts and
      behaviours. We identify associations between aspects of cannabis use, MDD, and
      suicidal thoughts and behaviours and examine whether such associations persist
      after accounting for those predisposing factors, including genetic liability and
      early family environment, that are shared by identical twins who are discordant
      for cannabis exposure. Any residual association in such identical pairs might be
      indicative of individual-specific pathways that might be of a causal nature.
      METHODS: We did a logistic regression analysis of cannabis use from retrospective
      data on same-sex male and female twin pairs drawn from 3 studies that had
      recruited twins from the Australian Twin Registry, 1992-93 (sample 1), 1996-2000
      (sample 2), and 2005-09 (sample 3). We studied associations between early use and
      frequent use of cannabis and MDD, suicidal ideation (ever and persistent), and
      suicide plan and attempt in the full sample as well as in pairs of monozygotic
      and dizygotic twins that were discordant for each measure of cannabis involvement
      at a single timepoint. Significant monozygotic associations were further adjusted
      for covariates, such as early alcohol or nicotine use, early dysphoric or
      anhedonic mood, conduct disorder, and childhood sexual abuse. Interactions
      between each cannabis measure and sex, sample or study effects, and birth year
      category were also examined as covariates. FINDINGS: In 13 986 twins (6181
      monozygotic and 7805 dizygotic), cannabis use ranged from 1345 (30.4%) of 4432
      people in sample 1 to 2275 (69.0%) of 3299 in sample 3. Mean age of first
      cannabis use ranged from 17.9 years (SD 3.3) in sample 3 to 21.1 years (5.2) in
      sample 1, and frequent use (>=100 times) was reported by 214 (15.9%) of 1345
      users in sample 1 and 499 (21.9%) of 2275 in sample 3. The prevalence of suicidal
      ideation ranged from 1102 (24.9%) of 4432 people in sample 1 to 1644 (26.3%) of
      6255 people in sample 2 and 865 (26.2%) of 3299 people in sample 3. Prevalence of
      MDD ranged from 901 (20.3%) people in sample 1 to 1773 (28.3%) in sample 2. The
      monozygotic twin who used cannabis frequently was more likely to report MDD (odds
      ratio 1.98, 95% CI 1.11-3.53) and suicidal ideation (2.47, 1.19-5.10) compared
      with their identical twin who had used cannabis less frequently, even after
      adjustment for covariates. For early cannabis use, the monozygotic point estimate
      was not significant but could be equated to the significant dizygotic estimate,
      suggesting a possible association with suicidal ideation. INTERPRETATION: The
      increased likelihood of MDD and suicidal ideation in frequent cannabis users
      cannot be solely attributed to common predisposing factors. FUNDING: National
      Institute on Drug Abuse, National Institutes of Health, Australian National
      Health and Medical Research Council.

PMID- 28750824
TI  - SYNTAX Score and Pre- and Poststent Optical Coherence Tomography Findings in the
      Left Anterior Descending Coronary Artery in Patients With Stable Angina Pectoris.
AB  - SYNTAX score (SS) has been reported to be an independent predictor of future
      cardiac events including target lesion revascularization. The aim of this study
      was to assess the relation between SS and plaque characteristics and poststent
      vascular response using optical coherence tomography in coronary artery tree and
      left anterior descending artery (LAD) in patients with stable angina. A total of
      179 lesions among 165 patients, including 100 lesions in LAD, were analyzed.
      Patients were stratified into tertiles. In pre-percutaneous coronary intervention
      analysis of whole coronary tree and LAD, lesions of the third tertile had the
      highest prevalence of lipid-rich plaque. Compared with the first tertile, the
      third tertile had greater lipid index, thinner fibrous cap, and higher prevalence
      of thin-cap fibroatheroma. In poststent optical coherence tomography, the
      incidence of stent edge dissection and irregular protrusion was higher in the
      third tertile compared with the first tertile in coronary tree analysis. In LAD
      analysis, the prevalence of irregular protrusion was the highest in the third
      tertile. In conclusion, high SS may reflect higher plaque vulnerability. Stent
      edge dissection and irregular protrusion were more frequent in patients with
      higher SS, indicating poor vascular response to stenting. Our results may explain
      higher cardiac event rate and target lesion revascularization in patients with
      higher SS.

PMID- 28750826
TI  - Cardiology 1919-1941 and Cardiology Today.

PMID- 28750825
TI  - Differences in Natriuretic Peptide Levels by Race/Ethnicity (From the Multi
      Ethnic Study of Atherosclerosis).
AB  - Natriuretic peptides (NP) are cardiac-derived hormones with favorable
      cardiometabolic actions. Low NP levels are associated with increased risks of
      hypertension and diabetes mellitus, conditions with variable prevalence by race
      and ethnicity. Heritable factors underlie a significant proportion of the
      interindividual variation in NP concentrations, but the specific influences of
      race and ancestry are unknown. In 5597 individuals (40% white, 24% black, 23%
      Hispanic, and 13% Chinese) without prevalent cardiovascular disease at baseline
      in the Multi-Ethnic Study of Atherosclerosis, multivariable linear regression and
      restricted cubic splines were used to estimate differences in serum N-terminal
      pro B-type natriuretic peptide (NT-proBNP) levels according to, ethnicity, and
      ancestry. Ancestry was determined using genetic ancestry informative markers. NT
      proBNP concentrations differed significantly by race and ethnicity (black, median
      43 pg/ml [interquartile range 17 to 94], Chinese 43 [17 to 90], Hispanic 53 [23
      to 107], white 68 [34 to 136]; p = 0.0001). In multivariable models, NT-proBNP
      was 44% lower (95% confidence interval -48 to -40) in black and 46% lower (-50 to
      -41) in Chinese, compared with white individuals. Hispanic individuals had
      intermediate concentrations. Self-identified blacks and Hispanics were the most
      genetically admixed. Among self-identified black individuals, a 20% increase in
      genetic European ancestry was associated with 12% higher (1% to 23%) NT-proBNP.
      Among Hispanic individuals, genetic European and African ancestry were positively
      and negatively associated with NT-proBNP levels, respectively. In conclusion, NT
      proBNP levels differ according to race and ethnicity, with the lowest
      concentrations in black and Chinese individuals. Racial and ethnic differences in
      NT-proBNP may have a genetic basis, with European and African ancestry associated
      with higher and lower NT-proBNP concentrations, respectively.

PMID- 28750827
TI  - Outcomes for Atrial Fibrillation Patients with Silent Left Atrial Thrombi
      Detected by Transesophageal Echocardiography.
AB  - Although we have occasionally experienced silent thrombi in the left atrium (LA),
      defined as thrombi free from embolic events, by screening transesophageal
      echocardiography (TEE) for atrial fibrillation (AF), few data are available on
      predictors and outcomes of silent LA thrombi in patients with AF. We
      retrospectively reviewed clinical records and identified 83 patients (2.6%) with
      silent LA thrombi, out of 4,214 TEE procedures in 3,139 patients with AF at 6
      hospitals from January 2010 to December 2012. The median [interquartile range]
      CHA2DS2-VASc score was 3 [2, 5]. Most patients (n = 71, 86%) were taking oral
      anticoagulants before the TEE, and 59 patients (71%) had heart failure (HF).
      During follow-up periods of 905 [620, 1301] days, ischemic stroke and systemic
      embolism, and hemorrhagic stroke occurred only in 3 (3.6%) and 2 patients (2.4%),
      respectively. All-cause death developed in 14 patients (17%), and cardiac death
      was the primary cause of death (n = 9, 11%). Multivariate Cox regression analysis
      showed the composite end point of death, stroke, systemic embolism, and major
      bleeding was significantly associated with age (hazard ratio; 1.06, 95%
      confidence interval; 1.01 to 1.11, p = 0.019) and HF (3.18, 1.27 to 7.99, p =
      0.014). In conclusion, the incidence of ischemic stroke after detecting silent LA
      thrombi was relatively low in patients with AF under oral anticoagulation.
      Advanced age and HF were predictors for worse outcomes in AF patients with silent
      LA thrombi.

PMID- 28750828
TI  - Efficacy and Safety of Alirocumab Versus Ezetimibe Over 2 Years (from ODYSSEY
      COMBO II).
AB  - The proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been
      shown to substantially reduce low-density lipoprotein cholesterol (LDL-C).
      Demonstrating whether efficacy and safety are maintained over a long duration of
      exposure is vital for clinical decision-making. The COMBO II trial compared the
      efficacy and safety of alirocumab versus ezetimibe over 2 years. A prespecified
      first analysis was reported at 52 weeks. Here we report the final end-of-study
      data (on-treatment) and evaluate post hoc the safety profile with longer versus
      shorter duration of alirocumab exposure. Patients (n = 720) on maximally
      tolerated statin dose were treated with alirocumab (75/150 mg every 2 weeks) or
      ezetimibe (10 mg/day). Overall mean adherence for both treatment groups during
      the first and second year was >97%. At 2 years, LDL-C was reduced by 49%
      (alirocumab) versus 17% (ezetimibe; p <0.0001), and LDL-C <70 mg/dl was achieved
      by 73% of alirocumab-treated versus 40% of ezetimibe-treated patients. Overall
      safety was similar in both treatment groups at 2 years and during the first
      versus the second year. Local injection-site reactions were reported by 2.5%
      (alirocumab) versus 0.8% (ezetimibe) during the first year, and 0.2% versus 0.5%
      during the second year, indicating early occurrence during prolonged alirocumab
      exposure. Two consecutive calculated LDL-C values <25 mg/dl were observed in 28%
      of alirocumab-treated patients (vs 0.4% with ezetimibe). Persistent anti-drug
      antibody responses were observed in 1.3% (6 of 454) of alirocumab-treated versus
      0.4% (1 of 231) of ezetimibe-treated patients. Neutralizing antibodies (that
      inhibit binding in vitro) were observed in 1.5% (7 of 454) of alirocumab-treated
      patients (0 with ezetimibe), mostly at isolated time points. Alirocumab sustained
      substantial LDL-C reductions and was well tolerated up to 2 years in the COMBO II
      trial.

PMID- 28750829
TI  - Editorial commentary: Arrhythmias in patients with left ventricular assist
      devices: Pump fixed; rhythm ... not so much.

PMID- 28750830
TI  - Appropriate dosing of nonvitamin K antagonist oral anticoagulants for stroke
      prevention in atrial fibrillation.
AB  - The development of nonvitamin K antagonist oral anticoagulants (NOACs) has been a
      major advance in therapy for patients requiring oral anticoagulation,
      particularly for long-term indications such as stroke prevention in atrial
      fibrillation (AF). The NOACs are generally easier to dose and manage due to less
      heterogeneity of effect across individuals and fewer drug and food interactions,
      compared with warfarin. However, the treatment effect of NOACs may vary based on
      important patient characteristics, particularly renal function. Therefore, the
      package inserts for these drugs have dosing recommendations for patients with
      impaired kidney function, which are frequently but not always based on evidence
      from large-scale, randomized, clinical trials. Furthermore, there is evidence
      that NOAC dosing inconsistent with the regulatory labeling may be associated with
      adverse clinical outcomes. This review discusses the evidence supporting the
      current NOAC dosing, current dosing practices, associated outcomes, and gaps in
      knowledge regarding use of NOACs in patients with AF.

PMID- 28750831
TI  - Potential role of tyrosine hydroxylase in the loss of psychostimulant effect of
      amphetamine under conditions of impaired dopamine transporter activity.
AB  - Amphetamine and methylphenidate are known to have stimulatory effect in healthy
      subjects but not in humans with attention deficit hyperactivity disorder and in
      rodents with impaired dopamine transporter (DAT) function. This phenomenon is
      called the paradoxical calming effect of psychostimulants. It has been previously
      demonstrated that psychostimulants may regulate the enzymatic activity of
      tyrosine hydroxylase (TH). Hence, the objective of the present study was to
      determine whether the lack of activity-stimulating effects of amphetamine in
      hyperactive rats is associated with changes in TH activity. To model
      hyperactivity in rats, acute administration of DAT inhibitor GBR12909 was used.
      Changes in TH activity, assessed as L-DOPA accumulation and TH phosphorylation
      levels, were measured in amphetamine treated rats with or without pretreatment
      with GBR12909. Our results showed that amphetamine treatment alone increased
      locomotor activity in rats, whereas pretreatment of rats with GBR12909
      counteracted this effect, a finding consistent with the paradoxical calming
      effect. GBR12909, while having no effect on its own, blocked amphetamine-induced
      elevation of TH activity in dorsal striatum and nucleus accumbens, measured as
      increased tissue L-DOPA concentration. However, the phosphorylation levels of TH
      were not affected by treatment with amphetamine, GBR12909 or the combination of
      both. Our findings indicate that other mechanisms than phosphorylation-regulated
      TH activity changes are responsible for the paradoxical calming effect of
      amphetamine under conditions of impaired DAT activity.

PMID- 28750832
TI  - Functional brain activation associated with working memory training and transfer.
AB  - While behavioural trials of working memory (WM) training have received much
      attention in recent years, a lesser explored parallel approach is functional
      neuroimaging. A small literature has suggested a complex time course for
      functional activation pattern changes following WM training (i.e. not simply
      increasing or decreasing due to training); however, no study to date has examined
      such neuroplastic effects in both the training task (dual n-back) and the fluid
      intelligence transfer task to which the training is purported to transfer
      (Raven's Matrices). This study investigated neural correlates of WM training in
      healthy young adults randomized to six weeks of WM training, or an active control
      condition (processing speed training) with a pre- and post-training fMRI design.
      Results indicated significant reductions in activation for the WM trained group
      in key WM-task related areas for trained WM tasks after training compared to the
      processing speed active control group. The same pattern of training related
      decreases in activation for the WM trained group was not observed for the
      transfer task, which is consistent with null results for all cognitive outcomes
      of the present trial. The observed pattern of results suggests that repetitive
      practice with a complex task does indeed lead to neuroplastic processes that very
      likely represent the reduced demand for attentional control while sub-components
      of the task become more routinized with practice. We suggest that future research
      investigate neural correlates of WM training in populations for which WM itself
      is impaired and/or behavioural trials of WM training have returned more promising
      results.

PMID- 28750833
TI  - Putting attention in the spotlight: The influence of APOE genotype on visual
      search in mid adulthood.
AB  - The Apolipoprotein E e4 allele is associated with greater cognitive decline with
      age, yet effects of this gene are also observed earlier in the lifespan. This
      research explores genotype differences (e2, e3, e4) in the allocation of
      visuospatial attention in mid-adulthood. Sixty-six volunteers, aged 45-55 years,
      completed two paradigms probing the active selection of information at the focus
      of attention (a dynamic scaling task) and perceptual capacity differences. Two
      methods of statistical comparison (parametric statistics, Bayesian inference)
      found no significant difference between e4 carriers and the homozygous e3 group
      on either the dynamic scaling or perceptual load task. E2 carriers, however,
      demonstrated less efficient visual search performance on the dynamic scaling
      task. The lack of an e4 difference in visuospatial attention, despite previous
      suggestion in the literature of genotype effects, indicates that select
      attentional processes are intact in e4 carriers in mid-adulthood. The association
      of e2 genotype with slower visual search performance complicates the premised
      protective effects of this allele in cognitive ageing.

PMID- 28750834
TI  - Protective effect of atorvastatin on d-galactose-induced aging model in mice.
AB  - Atorvastatin (Ator), competitive inhibitors of 3-hydroxymethyl-3-glutaryl
      coenzyme-A reductase, is a cholesterol lowering drug. Ator has been shown to have
      neuroprotective, antioxidant and anti-inflammatory properties making that a
      potential candidate for the treatment of central nervous system (CNS) disorders.
      Here we assessed the effect of Ator on the d-galactose (d-gal)-induced aging in
      mice. For this purpose, Ator (0.1 and 1mg/kg/p.o.), was administrated daily in d
      gal-received (500mg/kg/p.o.) mice model of aging for six weeks. Anxiety-like
      behaviors and cognitive functions were evaluated by the elevated plus-maze and
      novel object recognition tasks, respectively. Physical power was assessed by
      forced swimming capacity test. Animals brains were analyzed for the superoxide
      dismutase (SOD) and brain-derived neurotrophic factor (BDNF). We found that Ator
      decreases the anxiety-like behaviors in d-gal-treated mice. Also, our behavioral
      tests showed that Ator reverses the d-gal induced learning and memory impairment.
      Furthermore, we found that Ator increases the physical power of d-gal-treated
      mice. Our results indicated that the neuroprotective effect of Ator on d-gal
      induced neurotoxicity is mediated, at least in part, by an increase in the SOD
      and BDNF levels. The results of present study suggest that Ator could be used as
      a novel therapeutic strategy for the treatment of age-related conditions.

PMID- 28750836
TI  - A Likely Case of Limbic Encephalitis in a Patient With Voltage-Gated Potassium
      Channel Complex Antibody, Without a Known Antigenic Target: A Review of the
      Disease State and Value of Antibody Titers.

PMID- 28750835
TI  - Validation of a Nurse-Based Delirium-Screening Tool for Hospitalized Patients.
AB  - BACKGROUND: Guidelines recommend daily delirium monitoring of hospitalized
      patients. Available delirium-screening tools have not been validated for use by
      nurses among diverse inpatients. OBJECTIVE: We sought to validate the Nursing
      Delirium-Screening Scale (Nu-DESC) under these circumstances. METHODS: A blinded
      cross-sectional and quality-improvement study was conducted from August 2015
      February 2016. Nurses' Nu-DESC scores were compared to delirium diagnosis
      according to Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5)
      criteria. A total of 405 consecutive hospitalized patients were included. Nu-DESC
      positive (threshold score >=2) patients were matched with equal numbers of Nu
      DESC-negative patients, by sex, age, and nursing unit. Nurses recorded a Nu-DESC
      score for each patient on every 12-hour shift. A Nu-DESC-blinded evaluator
      interviewed patients for 2 consecutive days. Delirium diagnosis was determined by
      physicians using DSM-5 criteria applied to collected research data. Sensitivity
      and specificity of the Nu-DESC were calculated. In an exploratory analysis, the
      performance of the Nu-DESC was analyzed with the addition of bedside measures of
      attention. RESULTS: The sensitivity of the Nu-DESC at a threshold of >=2 was 42%
      (95% CI: 33-53%). Specificity was 98% (97-98%). At a threshold of >=1,
      sensitivity was 67% (52-80%) and specificity 93% (90-95%). Similar results were
      found with the addition of attention tasks. CONCLUSION: The Nu-DESC is a specific
      delirium detection tool, but it is not sensitive at the usually proposed cut
      point of >=2. Using a threshold of >=1 or adding a test of attention increase
      sensitivity with a minor decrease in specificity.

PMID- 28750837
TI  - EUS-guided gastroenterostomy: a multicenter study comparing the direct and
      balloon-assisted techniques.
AB  - BACKGROUND: EUS-guided gastroenterostomy (EUS-GE) is a developing modality in the
      management of gastric outlet obstruction (GOO) with several technical approaches,
      including the direct and balloon-assisted techniques. The aim of this study was
      to compare the direct with the balloon-assisted modality while further defining
      the role of EUS-GE in GOO. METHODS: This multicenter, retrospective study
      involved consecutive patients who underwent EUS-GE with the direct or balloon
      assisted technique for GOO (January 2014 to October 2016). The primary outcome
      was technical success. Secondary outcomes were success (ability to tolerate at
      least a full fluid diet), procedure time, and rate/severity of adverse events
      (AEs). RESULTS: A total of 74 patients (44.6% women; mean age 63.0 +/- 11.7
      years) underwent EUS-GE for GOO (direct gastroenterostomy, n = 52; balloon
      assisted gastroenterostomy, n = 22). GOO was of malignant and benign etiology in
      66.2% and 33.8% of patients, respectively. Technical success was achieved in
      94.2% of the direct and 90.9% of the balloon-assisted approach (P = .63). Mean
      procedure time was shorter with the direct technique (35.7 +/- 32.1 minutes vs
      89.9 +/- 33.3 minutes, P < .001). The clinical success rate was 92.3% for the
      direct technique and 90.9% for the balloon-assisted modality (P = 1.00), with a
      mean time to oral intake of 1.32 +/- 2.76 days. The AE rate was 6.8% with only 1
      severe AE noted. Rate of AEs, postprocedure length of stay, need for
      reintervention, and survival were similar between the 2 groups. CONCLUSIONS: EUS
      GE is effective and safe in the management of GOO. The direct technique may be
      the preferred method given its shorter procedure time when compared with the
      balloon-assisted approach. Prospective trials are needed to confirm these
      findings.

PMID- 28750838
TI  - Impact of mucosal inflammation on risk of colorectal neoplasia in patients with
      ulcerative colitis: a systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: Long-standing ulcerative colitis is an established risk
      factor for colorectal neoplasia. A number of observational studies have suggested
      that evidence of mucosal inflammation (endoscopic or histologic) is associated
      with a greater risk for colorectal neoplasia than is mucosal healing. Our goal
      was to systematically analyze the risk of colorectal neoplasia in patients with
      ulcerative colitis who have ongoing mucosal inflammation to better inform
      surveillance strategies. METHODS: We performed a systematic review and meta
      analysis of the effect of endoscopic and/or histologic inflammation on the risk
      of colorectal neoplasia in cohort and case-control studies. Sensitivity analyses
      for study setting and case definition were performed. RESULTS: Six studies met
      the inclusion criteria, incorporating outcomes in 1443 patients. No study used a
      single validated measure for mucosal inflammation. The pooled odds ratio for
      colorectal neoplasia was 3.5 (95% confidence interval [CI], 2.6-4.8; P < .001) in
      those with any mucosal inflammation and 2.6 (95% CI, 1.5-4.5; P = .01) in those
      with histologic inflammation, when compared with those with mucosal healing. The
      overall quality of the studies was good. CONCLUSION: The presence of objective
      evidence of mucosal inflammation during follow-up in patients with ulcerative
      colitis is associated with a greater risk of subsequent colorectal neoplasia than
      in those with mucosal healing. This risk factor should be considered in
      guidelines on surveillance intervals for these patients.

PMID- 28750839
TI  - Endoscopic treatment of fistulas after sleeve gastrectomy: a comparison of
      internal drainage versus closure.
AB  - BACKGROUND AND AIMS: Fistulas after sleeve gastrectomy are major adverse events
      of bariatric surgery. The endoscopic management strategy evolved from closure to
      internal drainage after 2013. The main objective of our study was to evaluate and
      compare these different approaches. METHODS: This retrospective study included
      all patients treated for fistulas after sleeve gastrectomy in a referral center.
      Closure management was defined as initial treatment that used a covered metal
      stent and/or endoclips. Internal drainage management was defined as initial
      treatment by nasocystic drain and/or a double-pigtail stent. RESULTS: A total of
      100 patients (women N = 78, mean [+/- standard deviation {SD}] age 42 +/- 12
      years) were included between 2007 and 2015. The mean (+/- SD) delay between
      sleeve gastrectomy and the first endoscopy was 82 +/- 125 days. The overall
      success of endoscopic treatment was 86% within 6 +/- 27 months. Two patients
      died. The primary success of internal drainage and closure management occurred in
      19 of 22 (86%) and 49 of 77 (63%) patients, respectively. Among patients in
      failure for closure management, 22 had secondary internal drainage (18 being
      successful). Success of initial management was significantly higher for internal
      drainage (P = .043). Factors associated with failure of closure management were
      in multivariable analysis: collection >5 cm (P = .013). Factors associated with a
      time >6 months for achieving leakage closure were in multivariable analysis:
      reoperation before endoscopy (P = .044) and purulent flow at endoscopy (P =
      .043). CONCLUSIONS: Endoscopic management of fistulas after sleeve gastrectomy
      was successful in 86% of cases. In cases of collections >5 cm, internal drainage
      should be proposed first. Surgical reintervention before endoscopy delays
      treatment success.

PMID- 28750840
TI  - Electroacupuncture-reduced sedative and analgesic requirements for diagnostic
      EUS: a prospective, randomized, double-blinded, sham-controlled study.
AB  - BACKGROUND AND AIMS: The role of electroacupuncture (EA) in reducing sedative and
      analgesic requirements during EUS is uncertain. The aim of this study was to
      investigate the efficacy of EA in reducing procedure-related pain and discomfort
      during EUS. METHODS: This was a double-blinded randomized controlled study
      conducted between March 2014 and July 2016. Consecutive patients who were
      scheduled for diagnostic EUS were recruited and randomized to receive EA or sham
      electroacupuncture (SA). The primary outcome was the dosage of propofol used.
      Other outcome measurements included pain scores, anxiety scores, satisfaction
      scores, patients' willingness to repeat the procedure, total procedure time, and
      adverse events. RESULTS: A total of 128 patients were recruited to the study. The
      patients who received EA had significantly fewer requirements for patient
      controlled sedation and analgesia (PCA). The median (interquartile range) number
      of demands for PCA (2 [1-5] vs 16.5 [8.5-33.8]; P < .001), the number of
      successful demands (2 [1-4] vs 9 [5.3-13]; P < .001), and the total dose of
      propofol (0.15 [0.08-0.34] vs 0.77 [0.38-1.09]; P < .001) and alfentanil (0.38
      [0.20-0.86] vs 1.92 [0.94-2.72]; P < .001) were all significantly less. Patients
      who received EA also had significantly lower procedural pain scores and anxiety
      scores (P < .001), and higher satisfaction scores (P < .001), and they were more
      willing to repeat the procedure (P < .001). Being in the SA group and the
      procedure time were significant predictors of increased PCA demands (P < .001 and
      P = .009, respectively). CONCLUSIONS: In conclusion, the use of EA reduced
      sedative and analgesia demands, improved patient experience, and was associated
      with a low risk of adverse events during diagnostic EUS. (Clinical trial
      registration number: NCT02066194.).

PMID- 28750841
TI  - [Scientific publications by research directors of medical schools in Peru].

PMID- 28750842
TI  - Exploring the role of social capital in urban citizens' initiatives in the
      Netherlands.
AB  - OBJECTIVE: This research explores the role of social capital in urban citizens'
      initiatives in the Netherlands, by using in-depth interviews. METHOD: Social
      capital was operationalized as shared norms and values, connectedness, trust and
      reciprocity. RESULTS: The findings show that initiatives form around a shared
      idea or ambition (shared norms and values). An existing network of relationships
      (connectedness) is needed for an idea to emerge and take form. Connectedness can
      also increase as a result of an initiative. Some level of trust between people
      needs to be present from the start of the initiative. For the initiative to
      persist, strong in-group connections seem important, as well as a good balance
      between investments and returns. This reciprocity is mainly about intangible
      assets, such as energy and friendship. CONCLUSION: This study concludes that
      social capital within citizens' initiatives is both a prerequisite for the
      formation of initiatives and a result of the existence of initiatives.

PMID- 28750843
TI  - The Disruptive Radiologist.

PMID- 28750844
TI  - The ACGME Supports Small Programs.

PMID- 28750845
TI  - Meaningful Work.

PMID- 28750846
TI  - Patient Financial Responsibility Reduces Use of Digital Breast Tomosynthesis
      Screening Mammography.

PMID- 28750847
TI  - Balancing the Risks of Radiation and Anesthesia in Pediatric Patients.

PMID- 28750848
TI  - Who Moved My Films?

PMID- 28750849
TI  - Heterogeneity in application, design, and analysis characteristics was found for
      controlled before-after and interrupted time series studies included in Cochrane
      reviews.
AB  - OBJECTIVES: The aim of the study was to examine the application, design, and
      analysis characteristics of controlled before-after (CBA) and interrupted time
      series (ITS) studies and their use in Cochrane reviews. STUDY DESIGN AND SETTING:
      We searched the Cochrane library for reviews including these study designs from
      May 2012 to March 2015 and purposively selected, where available, two reviews
      each across 10 prespecified intervention types. We randomly selected two CBA and
      two ITS studies from each review. Two researchers independently extracted
      information from the studies and the respective reviews. RESULTS: Sixty-nine
      reviews considered CBA and ITS studies for inclusion. We analyzed 21 CBA and 16
      ITS studies from 11 to 8 reviews, respectively. Cochrane reviews inconsistently
      defined and labeled CBA and ITS studies. Many studies did not meet the Cochrane
      definition or the minimum criteria provided by Cochrane Effective Practice and
      Organisation of Care. The studies present a heterogeneous set of study features
      and applied a large variety of analyses. CONCLUSION: While CBA and ITS studies
      represent important study designs to evaluate the effects of interventions,
      especially on a population or organizational level, unclear study design features
      challenge unequivocal classification and appropriate use. We discuss options for
      more specific definitions and explicit criteria for CBA and ITS studies.

PMID- 28750851
TI  - Phytogeographic patterns and cryptic diversity in an aposematic toad from NW
      Argentina.
AB  - The Yungas Redbelly Toad, Melanophryniscus rubriventris, is patchily distributed
      in Argentina, confined to the upland portion (1000-2000m above sea level) of the
      montane forests of northern and central regions of Salta, and in central-eastern
      and south-eastern Jujuy. This species is known for its striking aposematic color
      variation across its geographic distribution, and was once treated as a complex
      of three subspecies based on distinctive color patterns. Here we assess the
      geographical genetic variation within M. rubriventris and quantify divergence in
      color and pattern among individuals sampled from Northwestern Argentina. We
      compare multi-gene phylogeography of M. rubriventris to patterns of dorsal and
      ventral coloration to test whether evolutionary affinities predict variation in
      warning color. Our results reveal two well-supported species lineages: one
      confined to the extreme northern portion of our sampling area, and the other
      extending over most of the Argentine portion of the species' range, within which
      there are two populations. However, these well-supported evolutionary
      relationships do not mirror the marked variation in warning coloration. This
      discordance between DNA genealogy and warning color variation may reflect
      selection brought about by differences in local predation pressures, potentially
      coupled with effects of sexual selection and thermoregulation.

PMID- 28750850
TI  - Mitochondria targeting by environmental stressors: Implications for redox
      cellular signaling.
AB  - Mitochondria are cellular powerhouses as well as metabolic and signaling hubs
      regulating diverse cellular functions, from basic physiology to phenotypic fate
      determination. It is widely accepted that reactive oxygen species (ROS) generated
      in mitochondria participate in the regulation of cellular signaling, and that
      some mitochondria chronically operate at a high ROS baseline. However, it is not
      completely understood how mitochondria adapt to persistently high ROS states and
      to environmental stressors that disturb the redox balance. Here we will review
      some of the current concepts regarding how mitochondria resist oxidative damage,
      how they are replaced when excessive oxidative damage compromises function, and
      the effect of environmental toxicants (i.e. heavy metals) on the regulation of
      mitochondrial ROS (mtROS) production and subsequent impact.

PMID- 28750852
TI  - Assessment of biosecurity and control measures to prevent incursion and to limit
      spread of emerging transboundary animal diseases in Europe: An expert survey.
AB  - Decision-makers and risk managers are often called upon to prioritise on and
      recommend suitable measures to prevent the risk of introduction and spread of
      pathogens. The main objective of this study was to assess the perceptions of
      experts in Italy, Switzerland and the United Kingdom concerning the importance,
      effectiveness, feasibility, costs and acceptability of selected biosecurity
      measures to prevent the introduction and limit the spread of rabies, blue tongue
      (BT) and classical swine fever (CSF). After identifying the most relevant
      measures by the project team, an expert knowledge elicitation was implemented
      through a questionnaire. After preliminary descriptive analyses, a number of
      statistical calculations were performed such as weighted medians, Spearman rank
      correlation tests, Wilcoxon comparison tests and ranking of measures. Three
      experts from each country completed the questionnaires, one expert for each
      disease. The mean answer rates for CSF, BT and rabies were 73%, 100% and 99%
      respectively. "Tracing system for live animal trade" was highlighted as very
      relevant in all diseases. The implementation of a "restriction zone after a
      suspicion or confirmation" was also rated as a relevant measure, especially for
      CSF. We identified generally a small correlation between costs and the other
      criteria. Among the rabies experts, measures related to "zoonotic risk" were
      rated highly, supporting the idea of a One Health approach. Disagreement among
      experts concerned 43 measures for the three pathogens: the debated measures were
      "control of the wildlife CSF status", "arthropod-vector control" and "rabies
      vaccination for domestic animals". Facing budget restriction, decision-makers
      need to prioritise their actions and make efficient prevention choices. With this
      study, we aimed to provide elements for reflection and to inform priority
      setting. The results can be applied through the implementation of similar surveys
      or directly from the knowledge already gathered in this study.

PMID- 28750853
TI  - Human papillomavirus vaccination and risk of autoimmune diseases: A large cohort
      study of over 2million young girls in France.
AB  - BACKGROUND: Whether human papillomavirus (HPV) vaccination could induce or
      trigger autoimmune diseases (AID) has been questioned, and potentially
      contributes to low immunization coverage in France. This study evaluated the
      association between HPV vaccination and the risk of AID using routinely collected
      data sources. METHODS: All girls aged 13-16years between 2008 and 2012, covered
      by the general health insurance scheme and without history of HPV vaccination or
      AID, were included and followed using French nationwide databases. Fourteen
      neurological, rheumatological, haematological, gastrointestinal or endocrine AID,
      were identified from ICD-10 codes allocated to hospital stays and long-term
      illnesses or by marker drugs. Their incidence was compared between girls exposed
      and non-exposed to HPV vaccination, using a Cox model adjusted for inclusion
      year, geographic area, socio-economic indicators, healthcare use level and other
      immunizations. RESULTS: Among 2,252,716 girls, 37% received HPV vaccine and 4,096
      AID occurred during a mean follow-up time of 33months. The incidence of AID was
      not increased after exposure to HPV vaccination, except for Guillain-Barre
      syndrome (GBS) (incidence rate of 1.4 among exposed [20 cases] versus 0.4 per
      100,000 PY among unexposed [23 cases]; adjusted HR: 3.78 [1.79-7.98]). This
      association persisted across numerous sensitivity analyses and was particularly
      marked in the first months following vaccination. Under the hypothesis of a
      causal relationship, this would result in 1-2 GBS cases attributable to HPV
      vaccine per 100,000 girls vaccinated. CONCLUSIONS: Our study provides reassuring
      results regarding the risk of AID after HPV vaccination, but an apparently
      increased risk of GBS was detected. Further studies are warranted to confirm this
      finding.

PMID- 28750855
TI  - Assessment of the duplicate notifiable reporting of hepatitis B infection in
      Zhejiang province, China, 2005-2015.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection control has seen improvements since
      the introduction of the HBV vaccination program in China. However, the reported
      incidence rate of HBV infection remains high owing to the large pool of
      individuals infected before the start of the HBV immunization program. The
      duplicated reporting of HBV had a remarkable effect on the overestimation of HBV
      disease burden, according to the Chinese National Notifiable Diseases Report
      System (NNDRS). METHODS: We analyzed the data of HBV in Zhejiang province, China,
      collected for the years 2005-2015 from the NNDRS. The duplicate reporting cases
      of HBV were captured according to the same identification number or the same
      name, sex and date of birth, or the same name, sex and resident town/street code.
      We assessed the magnitude of duplicated reporting of HBV and explored the
      possible factors contributing to duplicated reporting. RESULTS: There were 20,078
      redundant HBV cases reported from the NNDRS during 2005-2015, which accounted for
      6.33% (19,272/305,654) of all patients owing to duplicate reporting in Zhejiang
      province, China. Some risk factors, including male sex, age >=20years, chronic
      cases, residence in outside counties, and farming as an occupation (odds ratio
      [OR]=1.06; 95% confidence interval [CI]: 1.02-1.11) were positively associated
      with the risks on duplicate reporting. CONCLUSIONS: Our results demonstrated that
      the duplicated reporting of HBV infection is common in Zhejiang, China, which has
      contributed to a higher HBV infection prevalence than its real value. Some
      characteristics might affect the probability of duplicate reporting, including
      sex, occupation, place of residence, HBV type, and hospital type. These findings
      indicated the strong need to improve the data collection, deletion of
      duplications, and HBV classification during HBV surveillance, in order to obtain
      an accurate estimate of HBV disease burden in China. We also suggest establishing
      a specialized system to achieve high-quality HBV infection surveillance
      effectively and practically.

PMID- 28750854
TI  - Tularemia vaccine: Safety, reactogenicity, "Take" skin reactions, and antibody
      responses following vaccination with a new lot of the Francisella tularensis live
      vaccine strain - A phase 2 randomized clinical Trial.
AB  - BACKGROUND: Tularemia is caused by Francisella tularensis, a gram-negative
      bacterium that has been weaponized as an aerosol. For protection of personnel
      conducting biodefense research, the United States Army required clinical
      evaluation of a new lot of tularemia live vaccine strain manufactured in
      accordance with Current Good Manufacturing Practices. METHODS: A phase 2
      randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine
      that has been in use for decades (USAMRIID-LVS). The vaccines were delivered by
      scarification to 228 participants. Safety, reactogenicity, take and/or antibody
      levels were assessed on days 0, 1, 2, 8, 14, 28, 56, and 180. PRINCIPAL RESULTS:
      Both vaccines were safe and had acceptable reactogenicity profiles during six
      months of follow-up. There were no serious or grade 3 and 4 laboratory adverse
      events. Moderate systemic reactogenicity (mostly headache or feeling tired) was
      reported by ~23% of participants receiving either vaccine. Injection site
      reactogenicity was mostly mild itchiness and pain. The frequencies of vaccine
      take skin reactions were 73% (95% CI, 64, 81) for DVC-LVS and 80% (95% CI, 71,
      87) for USAMRIID-LVS. The 90% CI for the difference in proportions was -6.9% (
      16.4, 2.6). The rates of seroconversion measured by microagglutination assay on
      days 28 or 56 were 94% (95% CI, 88, 98; n=98/104) for DVC-LVS and 94% (95% CI,
      87, 97; n=103/110) for USAMRIID-LVS (p=1.00). Day 14 sera revealed more rapid
      seroconversion for DVC-LVS relative to USAMRIID-LVS: 82% (95% CI, 73, 89) versus
      55% (95% CI, 45, 65), respectively (p<0.0001). MAJOR CONCLUSIONS: The DVC-LVS
      vaccine had similar safety, reactogenicity, take and antibody responses compared
      to the older USAMRIID vaccine, and was superior for early (day 14) antibody
      production. Vaccination take was not a sensitive surrogate for seroconversion in
      a multi-center study where personnel at five research clinics performed
      assessments. ClinicalTrials.gov identifier NCT01150695.

PMID- 28750856
TI  - Readability of Patient Education Materials From the Web Sites of Orthopedic
      Implant Manufacturers.
AB  - BACKGROUND: Prior studies indicate that orthopedic patient education materials
      are written at a level that is too high for the average patient. The purpose of
      this study was to assess the readability of online patient education materials
      provided by orthopedic implant manufacturers. METHODS: All patient education
      articles available in 2013 from the web sites of the 5 largest orthopedic implant
      manufacturers were identified. Each article was evaluated with the Flesch-Kincaid
      (FK) readability test. The number of articles with readability <= the eighth
      grade level (average reading ability of US adults) and the sixth-grade level
      (recommended level for patient education materials) was determined. Mean
      readability levels of each company's articles were compared using analysis of
      variance (significance set at P < .05). RESULTS: A total of 581 articles were
      reviewed from the 5 largest implant manufacturers. The mean overall FK grade
      level was 10.9 (range, 3.8-16.1). Only 58 articles (10%) were written <= the
      eighth-grade level, and only 13 (2.2%) were <= the sixth-grade level. The mean FK
      grade level was significantly different among groups (Smith & Nephew = 12.0,
      Stryker = 11.6, Biomet = 11.3, DePuy = 10.6, Zimmer = 10.1; P < .0001).
      CONCLUSION: The majority of patient education materials from implant
      manufacturers are written at a level too high to be comprehended by the average
      patient. Future efforts should be made to improve the readability of orthopedic
      patient education materials.

PMID- 28750857
TI  - Interventions for Improving Hip Resurfacing Outcomes in Women: A High-Volume,
      Retrospective Study.
AB  - BACKGROUND: Women seeking surgical intervention for their hip disorders will
      often find total hip arthroplasty (THA) presented as their only option. THA, when
      compared with hip resurfacing arthroplasty, removes substantially more bone
      stock, limits range-of-motion, exhibits increased dislocation risk, and presents
      greater overall 10-year mortality rate. Despite these risks, most surgeons
      continue to select against women for hip resurfacing because registries
      notoriously report inferior survivorship when compared with men and THA. METHODS:
      We investigated the reasons for why resurfacing arthroplasty devices survive
      poorly in women to develop interventions which might improve hip resurfacing
      outcomes in women. Using these findings, we developed a series of surgical
      interventions to treat the underlying issues. Herein, we compare 2 study groups:
      women who received hip resurfacings before (group 1) and after (group 2) these
      interventions. RESULTS: Eight-year implant survivorship substantially improved
      from 89.6% for group 1 to 97.7% for group 2. Adverse wear-related failure,
      femoral component loosening, and acetabular component loosening were all
      significantly reduced in group 2, which we attribute to the implementation of our
      relative acetabular inclination limit guidelines, use of uncemented femoral
      fixation, and selection of the Tri-Spike acetabular component for supplemental
      fixation, respectively. Kaplan-Meier implant survivorship curves, grouped into 2
      year time intervals, show that the disparity in failure rates between men and
      women is diminishing. CONCLUSION: When experienced surgeons use refined and
      proper surgical technique, women show promise as excellent candidates for hip
      resurfacing as an alternative treatment for their debilitating hip conditions.

PMID- 28750858
TI  - Differences in Trochlear Surface Damage and Wear Between Three Different Total
      Knee Arthroplasty Designs.
AB  - INTRODUCTION: Trochlear design plays a role in patellofemoral kinematics. Little
      is known regarding differences in the contact properties between modern designs.
      The purpose of the present study was to analyze patellofemoral joint contact by
      identifying areas of joint surface damage and wear in retrieved femoral
      components of 3 modern designs. MATERIALS: Eighteen retrieved femoral components
      featuring 3 different modern designs (Triathlon, SIGMA, and GENESIS II) were
      matched based on time-in-vivo, age, gender, and body mass index. Trochlear wear
      and surface damage were assessed using visual inspection, light microscopy, and
      light profilometry. RESULTS: Visual inspection of the femoral components showed
      evidence of surface damage in all implant types. No significant differences
      between the groups were found with respect to surface damage and wear on visual
      inspection. Light profilometry of retrieved components showed that retrieved
      Triathlon (P = .002) and SIGMA (P = .009) components were significantly rougher
      than the corresponding reference components. The GENESIS II retrieved components
      were not substantially rougher than the reference components (P = .48). Light
      profilometry analysis showed significantly increased roughness of retrieved SIGMA
      components compared with Triathlon or GENESIS II components, particularly in the
      proximal trochlear groove and the medial trochlea. CONCLUSION: As the volume and
      patient demands for total knee arthroplasty increase, a greater understanding of
      the patellofemoral joint is warranted. Patellofemoral kinematics can have an
      effect on the surface characteristics of total knee arthroplasty components.
      Retrieved SIGMA components appeared to have increased roughness compared with
      Triathlon or GENESIS II components. The etiology and long-term effects of
      increased trochlear roughness require further investigation.

PMID- 28750859
TI  - Reply to letter to the editor.

PMID- 28750860
TI  - Impaired Barrier Function and Autoantibody Generation in Malnutrition Enteropathy
      in Zambia.
AB  - Intestinal damage in malnutrition constitutes a threat to the survival of many
      thousands of children globally. We studied children in Lusaka, Zambia, with
      severe acute malnutrition (SAM) and persistent diarrhea using endoscopy, biopsy
      and analysis of markers and protective proteins in blood and intestinal
      secretions. We carried out parallel investigations in apparently healthy adults,
      and analyzed biomarkers only in apparently healthy children. Villus height and
      crypt depth did not differ in children with SAM and adult controls, but
      epithelial surface was reduced in children with SAM (median 445, interquartile
      range (IQR) 388, 562MUm per 100MUm muscularis mucosae) compared to adults (578,
      IQR 465,709; P=0.004). Histological lesions and disruptions of claudin-4 and E
      cadherin were most pronounced in children with SAM. Circulating
      lipopolysaccharide, a marker of bacterial translocation, was higher in
      malnourished children (251, IQR 110,460EU/ml) than in healthy children (51, IQR
      0,111; P=0.0001). Other translocation markers showed similar patterns. Anti
      Deamidated Gliadin Peptide IgG concentrations, although within the normal range,
      were higher in children with SAM (median 2.7U/ml, IQR 1.5-8.6) than in adults
      (1.6, 1.4-2.1; P=0.005), and were inversely correlated with villus height (rho=
      0.79, n=13, P=0.001). Malnutrition enteropathy is associated with intestinal
      barrier failure and immune dysregulation.

PMID- 28750861
TI  - The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human
      Acute Myeloid Leukemia Cells.
AB  - Acute myeloid leukemia (AML) is a severe and often fatal systemic malignancy.
      Malignant cells are capable of escaping host immune surveillance by inactivating
      cytotoxic lymphoid cells. In this work we discovered a fundamental molecular
      pathway, which includes ligand-dependent activation of ectopically expressed
      latrophilin 1 and possibly other G-protein coupled receptors leading to increased
      translation and exocytosis of the immune receptor Tim-3 and its ligand galectin
      9. This occurs in a protein kinase C and mTOR (mammalian target of rapamycin)
      dependent manner. Tim-3 participates in galectin-9 secretion and is also released
      in a free soluble form. Galectin-9 impairs the anti-cancer activity of cytotoxic
      lymphoid cells including natural killer (NK) cells. Soluble Tim-3 prevents
      secretion of interleukin-2 (IL-2) required for the activation of cytotoxic
      lymphoid cells. These results were validated in ex vivo experiments using primary
      samples from AML patients. This pathway provides reliable targets for both highly
      specific diagnosis and immune therapy of AML.

PMID- 28750862
TI  - Alteration of haemostatic parameters in uncomplicated canine babesiosis.
AB  - Babesiosis is a tick-borne zoonotic disease caused by haemoprotozoan parasites.
      The aim of this study were to assess markers of coagulation pathways in 25 dogs
      with naturally occurring babesiosis caused by B. canis, compared to 10 healthy
      controls. Protein C (PC) and antithrombin III (AT III) activity were assessed
      using a chromogenic substrate test, while levels of thrombin-antithrombin (TAT)
      complexes, activated protein C (APC) and endothelial protein C receptor were
      assessed using canine-specific ELISA. AT III activity was decreased as a result
      of a negative acute phase response, degradation by elastase, reduced availability
      of glycosaminoglycans, and, most importantly, consumption as a consequence of
      thrombin formation. Procoagulant state and haemostatic shift towards thrombin
      formation are also demonstrated by elevated TAT levels. Regarding PC pathway only
      significant difference was found for APC. Taken together, haemostatic alterations
      in uncomplicated babesiosis represent a procoagulant state that is mostly
      reversed during treatment.

PMID- 28750863
TI  - Microscopic and molecular identification of hemotropic mycoplasmas in South
      American coatis (Nasua nasua).
AB  - Hemoplasmas were detected in two apparently healthy captive South American coatis
      (Nasua nasua) from southern Brazil during an investigation for vector-borne
      pathogens. Blood was subjected to packed cell volume (PCV) determination, a
      commercial real-time PCR panel for the detection of Anaplasma spp., Babesia spp.,
      Bartonella spp., Hepatozoon spp., Leishmania spp., Mycoplasma haemofelis,
      'Candidatus Mycoplasma turicensis', 'Candidatus Mycoplasma haemominutum',
      Neorickettsia risticii, Rickettsia rickettsii and Leptospira spp., and a pan
      hemoplasma conventional PCR assay. PCV was normal, but both coatis tested
      positive for hemoplasmas and negative for all the remaining pathogens tested.
      Using different techniques for microscopy (light, confocal or SEM), structures
      compatible with hemoplasmas were identified. Sequencing of the 16S rRNA gene
      identified an organism resembling Mycoplasma haemofelis and another hemotropic
      Mycoplasma sp., with a sequence identity of 96.8% to a Mycoplasma sp. previously
      detected in capybaras.

PMID- 28750864
TI  - Identification of a new diagnostic antigen for glanders using immunoproteome
      analysis.
AB  - Glanders is a disease of horses, donkeys and mules. The causative agent
      Burkholderia mallei, is a biorisk group 3 pathogen and is also a biothreat agent.
      Simple and rapid diagnostic tool is essential for control of glanders. Using a
      proteomic approach and immunoblotting with equine sera, we identified 12 protein
      antigens that may have diagnostic potential. Various immunoreactive proteins e.g.
      GroEL, translation elongation factor Tu, elongation factor Ts, arginine
      deiminase, malate dehydrogenase, DNA directed RNA polymerase subunit alpha were
      identified on 2-dimentional immunoblots. One of these proteins, GroEL, was cloned
      and expressed in E. coli and purified using Ni-NTA affinity chromatography. The
      recombinant GroEL protein was evaluated in ELISA format on a panel of glanders
      positive (n=49) and negative (n=79) equine serum samples to determine its
      diagnostic potential. The developed ELISA had a sensitivity and specificity of 96
      and 98.7% respectively. The results of this study highlight the potential of
      GroEL in serodiagnosis of glanders.

PMID- 28750865
TI  - Human head lice and pubic lice reveal the presence of several Acinetobacter
      species in Algiers, Algeria.
AB  - There are two majorspecies of medically important lice that parasitize humans:
      Phthirus pubis, found in pubic hair, and Pediculus humanus. Pediculus humanus
      consists of two eco types that live in specific niches on the human host: body
      lice (Pediculus humanus humanus), found on the human body and clothing, and head
      lice (Pediculus humanus capitis), found on the scalp. To date, only body lice are
      known to be vectors of human disease; however, it has recently been reported that
      the DNA of several bacterial agents has been detected in head lice, raising
      questions about their role in the transmission of pathogens. This issue caught
      our attention, in addition to the fact that the pathogenic bacteria associated
      with P. pubis and P. humanus capitis have never been investigated in Algeria. To
      investigate this,molecular techniques (real-time PCR) were used to screen for the
      presence of Acinetobacter spp., Bartonella spp., Borrelia spp. and Rickettsia
      prowazekii DNA from P. humanus capitis (64 lice) collected from
      schoolchildren,and P. pubis (4 lice),collected from one adultman living in
      Algiers. Positive samples for Acinetobacter spp.were identified by sequencing
      therpoBgene. Conventional PCR targeting the partial Cytb gene was used to
      determine the phylogenetic clade of the collected lice. Of the 64 samples
      collected, Acinetobacter spp. DNA was detected in 17/64 (27%) of head lice,
      identified as: A. baumannii (14%), A. johnsonii (11%) and A. variabilis (2%). Of
      the four P. pubissamples, 2(50%) were positive for A. johnsonii. The phylogenetic
      tree based on the Cytb gene revealed that P. humanus capitis were grouped into
      clades A and B. In this study, we report andidentify for the first time
      Acinetobacter spp.in Algerian P. pubis and P. humanus capitis. The detection of
      the genus Acinetobacter in lice should not be underestimated, especially in P.
      humanus capitis, which is distributed worldwide. However, additional
      epidemiological data are required to determine if human lice may act as an
      environmental reservoir and are actively involved in the propagation of these
      bacteria to humans.

PMID- 28750866
TI  - Two novel Ehrlichia strains detected in Amblyomma tigrinum ticks associated to
      dogs in peri-urban areas of Argentina.
AB  - The aim of this work was to describe two novel strains of Ehrlichia associated to
      Amblyomma tigrinum from Argentina. Molecular detection of agents belonging to the
      family Anaplasmataceae was performed targeting three different loci: 16S rRNA
      gene, dsb gene and a fragment of groESL heat shock operon. The results have shown
      that two different strains of Ehrlichia sp. associated to A. tigrinum are
      circulating in peri-urban areas of Argentina. The Ehrlichia strain detected in
      ticks from San Luis Province, named as Ehrlichia sp. strain San Luis, is closely
      related to the Ehrlichia chaffeensis. The novel Ehrlichia strain detected in
      Cordoba Province, named as Ehrlichia sp. strain Cordoba, is phylogenetically
      related to three Ehrlichia strains from Brazil, two of them isolated from wild
      carnivorous and the third one isolated from horse. Even though Ehrlichia sp.
      strain Cordoba was clustered with the three Ehrlichia strains from Brazil, the
      genetic similarity was too low to consider them as the same taxonomic entity.
      Blood samples of dogs were positive to Anaplasma platys. The association of these
      two novel strains with A. tigrinum has epidemiological relevance because adult
      stages of this tick species are common parasite of dogs in rural and peri-urban
      areas and they are aggressive to humans. The presence of these two novel
      Ehrlichia strains implies a potential epidemiological risk in Argentina because
      the species of the genus Ehrlichia are known to be pathogenic to both domestic
      mammals and humans.

PMID- 28750867
TI  - West Nile virus infection in horses, Indian ocean.
AB  - The circulation of West Nile virus (WNV) in horses was investigated in the
      Southwest Indian ocean. In 2010, blood samples were collected from a total of 303
      horses originating from Madagascar, Mauritius, Reunion and the Seychelles and
      tested for WNV-specific antibodies. An overall seroprevalence of 27.39% was
      detected in the Indian Ocean with the highest WNV antibody prevalence of 46.22%
      (95% CI: [37.4-55.2%]) in Madagascar. The age and origin of the horses were found
      to be associated with the WNV infection risk. This paper presents the first
      seroprevalence study investigating WN fever in horses in the Southwest Indian
      Ocean area and indicates a potential risk of infection for humans and animals. In
      order to gain a better understanding of WN transmission cycles, WNV surveillance
      needs to be implemented in each of the countries.

PMID- 28750868
TI  - Effect of colostrum quantity and quality on neonatal calf diarrhoea due to
      Cryptosporidium spp. infection.
AB  - This study was conducted to assess the effect of colostrum quality and quantity
      on Cryptosporidium spp. calf diarrhoea in an intensive dairy cattle farm in
      Greece. Faecal samples were collected from 100 dairy calves randomly selected and
      born during all 4 seasons (March 2015 to May 2016) of the year. In total, 71% of
      the selected calves were positive for Cryptosporidium spp. oocysts. The
      statistical analysis revealed influence of colostrum quality on faecal score.
      Linear regression showed that the colostrum quantity during the first day of life
      was negatively associated with the number of Cryptosporidium spp. oocysts in
      faeces. During multivariable analysis, the variables representing the quality of
      colostrum and the season of the calf's birth were identified as confounders.
      Cryptosporidium spp. is a common pathogen participating in neonatal calf
      diarrhoea. Colostrum management and season influence the number of
      Cryprosporidium spp. oocysts and faecal consistency. The above findings
      demonstrate novel risk factors that should be included in the strategic
      approaches to control cryptosporidiosis in newborn calves.

PMID- 28750869
TI  - Probiotic Lactobacillus acidophilus bacteria or synthetic TLR2 agonist boost the
      growth of chicken embryo intestinal organoids in cultures comprising epithelial
      cells and myofibroblasts.
AB  - The intestinal epithelial cells reside in close proximity to myofibroblasts and
      microbiota, which are supposed to have an impact on intestinal stem cells fate
      and to influence processes of tissue maturation and regeneration. Mechanism
      underlying these phenomena and their diversity among vertebrates can be studied
      in 3D organoid cultures. We investigated the growth of chicken embryo intestinal
      epithelial organoids in Matrigel with and without Toll-like receptors (TLRs)
      stimulation. The organoid cultures contained also some myofibroblasts with
      potential to promote intestinal stem cell survival. Organoid cells, expressing
      TLR4, TLR2 type 1 and TLR2 type 2 were incubated with their agonists
      (lipopolysaccharide - LPS and Pam3CSK4) or co-cultured with Lactobacillus
      acidophilus bacteria (LA-5). Pam3CSK4 and LA-5 promoted organoid growth, which
      was demonstrated by comparing the morphological parameters (mean number and area
      of organoids). The profile of prostaglandins (PG), known to promote intestinal
      regeneration, in supernatants from organoid and fibroblast cultures were
      evaluated. Both PGE2 and PGD2 were detected. As compared to unstimulated
      controls, supernatants from the Pam3CSK4-stimulated organoids contained twice as
      much of PGE2 and PGD2. The changes in production of prostaglandins and the
      support of epithelial cell growth by myofibroblasts are factors potentially
      responsible for stimulatory effect of TLR2 activation.

PMID- 28750870
TI  - [Impact of obesity in the pathophysiology of degenerative disk disease and in the
      morbidity and outcome of lumbar spine surgery].
AB  - Obesity (BMI>30Kg/m2) is a pandemic with severe medical and financial
      implications. There is growing evidence that relates certain metabolic processes
      within the adipose tissue, preferentially abdominal fat, with a low-intensity
      chronic inflammatory state mediated by adipokines and other substances that favor
      disk disease and chronic low back pain. Obesity greatly conditions both the
      preoperative evaluation and the spinal surgical technique itself. Some meta
      analyses have confirmed an increase of complications following lumbar spine
      surgery (mainly infections and venous thrombosis) in obese subjects. However,
      functional outcomes after lumbar spine surgery are favorable although inferior to
      the non-obese population, acknowledging that obese patients present with worse
      baseline function levels and the prognosis of conservatively treated obese
      cohorts is much worse. The impact of preoperative weight loss in spine surgery
      has not been prospectively studied in these patients.

PMID- 28750871
TI  - A multiplex assay for detection of SHIV plasma and mucosal IgG and IgA.
AB  - Evaluating antibody maturation provides valuable data to characterize immune
      responses to HIV infection and can provide insight into biomedical intervention
      efficacy. It is important to develop assays that evaluate antibody maturation in
      both plasma and mucosal compartments. The nonhuman primate model provides a
      controlled system to collect temporal data that are integral to assessing
      intervention strategies. We report the development of a novel multiplex assay,
      based on the Bio-Plex platform, to evaluate plasma and mucosal IgG and IgA
      avidity and maturation against simian/human immunodeficiency virus (SHIV) in this
      controlled system. Vaginal mucosa and plasma samples were collected from a prior
      study evaluating the efficacy of a tenofovir disoproxil fumarate (TDF)
      intravaginal ring (IVR) against SHIVSF162P3 challenge in female pigtailed
      macaques. For validation of the multiplex assay, specimens from six SHIV-infected
      placebo animals and one TDF breakthrough animal were evaluated. For SHIV and HIV
      envelope analytes, antibody levels and avidity in both compartments continued to
      mature post-infection. Maturation of IgG and IgA levels was similar in each
      compartment, however, mucosal antibody levels tended to be more variable. This
      SHIV assay elucidates IgG/IgA antibody kinetics in the plasma and vaginal mucosa
      and will be a valuable tool in vaccine and other biomedical intervention studies
      in the nonhuman primate model.

PMID- 28750872
TI  - A new index predicts early allograft dysfunction following living donor liver
      transplantation: A propensity score analysis.
AB  - OBJECTIVE/AIM: The aim of this study was to identify a new index to predict early
      allograft dysfunction following living donor liver transplantation. METHODS: The
      study enrolled 260 adult living donor liver transplantation recipients.
      Postoperative laboratory variables were assessed for their association with the
      prevalence of early allograft dysfunction using the inverse probability of
      treatment weighting and propensity-score matching (n=93 pairs) analysis. RESULTS:
      Forty-seven recipients (18.1%) developed early allograft dysfunction. In
      multivariable analysis, the alanine aminotransferase and gamma-glutamyl
      transpeptidase levels on postoperative day 1 were independent predictors of early
      allograft dysfunction. The alanine aminotransferase to gamma-glutamyl
      transpeptidase ratio (AGR) was developed. All cases were divided into two groups
      (Group 1 [AGR>=8.47, n=103] and Group 2 [AGR<8.47, n=157]). AGR>=8.47 (OR 10.345,
      95%CI 4.502-23.772, p<0.001), hepatorenal syndrome (OR 3.016, 95%CI 1.119-8.125,
      p=0.029), and graft to recipient weight ratio <0.8% (OR 2.155, 95%CI 1.004-4.624,
      p=0.049) were independent risk factors for early allograft dysfunction. The
      prevalence of early allograft dysfunction was higher in group 1 (after adjusting
      for inverse probability of treatment weighting [n=39; 37.9% vs n=8; 5.1%] and
      propensity-score matching [n=33; 35.5% vs n=2; 2.2%]) than that in group 2
      (p<0.001). CONCLUSIONS: The postoperative AGR is a practical index for predicting
      early allograft dysfunction after living donor liver transplantation.

PMID- 28750874
TI  - Guidelines on hyponatremia that not always guide.

PMID- 28750873
TI  - Mnemonic function in small vessel disease and associations with white matter
      tract microstructure.
AB  - Cerebral small vessel disease (SVD) is associated with deficits in working
      memory, with a relative sparing of long-term memory; function may be influenced
      by white matter microstructure. Working and long-term memory were examined in 106
      patients with SVD and 35 healthy controls. Microstructure was measured in the
      uncinate fasciculi and cingula. Working memory was more impaired than long-term
      memory in SVD, but both abilities were reduced compared to controls. Regression
      analyses found that having SVD explained the variance in memory functions, with
      additional variance explained by the cingula (working memory) and uncinate (long
      term memory). Performance can be explained in terms of integrity loss in specific
      white matter tract associated with mnemonic functions.

PMID- 28750875
TI  - Chronic kidney disease in hypertensive subjects >=60 years treated in Primary
      Care.
AB  - BACKGROUND: Hypertension (HT) is the second leading cause of kidney failure. In
      hypertensive patients with chronic kidney disease (CKD), blood pressure (BP)
      control is the most important intervention to minimise progression. For CKD
      diagnosis, standardised creatinine and estimated glomerular filtration rate
      (eGFR) testing by CKD-EPI is recommended. OBJECTIVES: To describe the prevalence
      and factors associated with a moderate decrease in eGFR (by CKD-EPI) and BP
      control in subjects with HT. METHODS: Cross-sectional descriptive study in
      subjects >= 60 years included in the SIDIAP plus database with hypertension and
      standardised serum creatinine and BP tests in the last 2years. EXCLUSION
      CRITERIA: eGFR<30, dialysis or kidney transplantation, prior cardiovascular
      disease, home care. Primary endpoint: eGFR by CKD-EPI formula. Covariates:
      demographic data, examination, cardiovascular risk factors, heart failure and
      auricular fibrillation diagnosis, and drugs (antihypertensive agents acting on
      renal function, antiplatelet and lipid lowering agents). BP control criteria:
      <=130/80mmHg in individuals with albuminuria, <=140/90 in all other subjects.
      RESULTS: Prevalence of eGFR <60=18.8%. Associated factors: age, gender, heart
      failure, albumin/creatinine ratio, auricular fibrillation, smoking,
      dyslipidaemia, diabetes and obesity. BP control: 66.14 and 63.24% in eGFR>=60 and
      eGFR <60, respectively (P<.05). Exposure to drugs was higher in eGFR<60.
      CONCLUSION: One in 5hypertensive patients without cardiovascular disease >=60
      years in primary care presented with a moderate decrease in eGFR. In addition to
      age and sex, albuminuria and heart failure were the main associated factors.
      Despite the increased exposure to drugs, BP control was lower in CKD.

PMID- 28750876
TI  - Acute renal failure in patients with myeloma: Experience with extended high cut
      off hemodialysis.

PMID- 28750877
TI  - Actinomyces viscosus infection in a kidney-pancreas trasplanted patient.

PMID- 28750878
TI  - Blood transfusion during haemodialysis improves systemic tissue oxygenation: A
      case report.

PMID- 28750879
TI  - Glomerular involvement in patient with sickle cell disease.

PMID- 28750880
TI  - Immuno complex mediated acute glomerulonephritis in a patient with infectious
      mononucleosis.

PMID- 28750881
TI  - Exophthalmos and hyperparathyroidism.

PMID- 28750882
TI  - Unrecognized failed airway management using a supraglottic airway device.
AB  - BACKGROUND: 911 Emergency Medical Services (EMS) systems utilize supraglottic
      devices for either primary advanced airway management, or for airway rescue
      following failed attempts at direct laryngoscopy endotracheal intubation. There
      is, however, limited data on objective confirmation of supraglottic airway
      placement in the prehospital environment. Furthermore, the ability of EMS field
      providers to recognize a misplaced airway is unknown. METHODS: Retrospective
      review of patients who underwent airway management using the King LTS-D
      supraglottic airway in a large urban EMS system, between 3/1/15-9/30/2015.
      Subjective success was defined as documentation of successful airway placement by
      the EMS provider. Objective success was confirmed by review of waveform
      capnography, with the presence of a 4-phase waveform greater than 5mmHg.
      Sensitivity and specificity of the field provider's assessment of success were
      then calculated. RESULTS: A total of 344 supraglottic airway attempts were
      reviewed. No patients met obvious death criteria. 269 attempts (85.1%) met
      criteria for both subjective and objective success. 19 attempts (5.6%) were
      recognized failures by the EMS provider. 47 (13.8%) airways were misplaced but
      unrecognized by the EMS provider. 4 attempts (1.2%) were correctly placed but
      misidentified as failures, leading to the unnecessary removal and replacement of
      the airway. Sensitivity of the provider's assessment was 98.5%; specificity was
      28.7%. CONCLUSION: The use of supraglottic airway devices results in unrecognized
      failed placement. Appropriate utilization and review of waveform capnography may
      remedy a potential blind-spot in patient safety, and systemic monitoring/feedback
      processes may therefore be used to prevent unrecognized misplaced airways.

PMID- 28750883
TI  - Delayed return of spontaneous circulation (the Lazarus phenomenon) after
      cessation of out-of-hospital cardiopulmonary resuscitation.
AB  - INTRODUCTION: The delayed return of spontaneous circulation (ROSC) after
      cessation of cardiopulmonary resuscitation (CPR), also known as the Lazarus
      phenomenon, is a rare event described in several case reports. This study aims to
      determine the incidence and the time of occurrence of the Lazarus phenomenon
      after cessation of out-of-hospital CPR. METHODS: This prospective observational
      cohort study was conducted in the Helsinki Emergency Medical Service in Finland
      from 1 January 2011 through 31 December 2016. All out-of-hospital CPR attempts
      were carefully monitored for 10min after the cessation of CPR in order to detect
      delayed ROSC. RESULTS: Altogether, 2102 out-of-hospital cardiac arrests occurred
      during the six-year study period. CPR was attempted in 1376 (65.5%) cases. In 840
      cases (61.0% of all attempts) CPR attempts were terminated on site. The Lazarus
      phenomenon occurred five times, with an incidence of 5.95/1000 (95% CI 2.10
      14.30) in field-terminated CPR attempts. Time to delayed ROSC from the cessation
      of CPR varied from 3 to 8min. Three of the five patients with delayed ROSC died
      at the scene within 2-15min while two died later in hospital within 1.5 and 26h,
      respectively. CONCLUSIONS: We observed that the Lazarus phenomenon is a real
      albeit rare event and can occur a few minutes after the cessation of out-of
      hospital CPR. We suggest a 10-min monitoring period before diagnosing death. CPR
      guidelines should be updated to include information of the Lazarus phenomenon and
      appropriate monitoring for it.

PMID- 28750884
TI  - Predictive value of EEG in postanoxic encephalopathy: A quantitative model-based
      approach.
AB  - INTRODUCTION: The majority of comatose patients after cardiac arrest do not
      regain consciousness due to severe postanoxic encephalopathy. Early and accurate
      outcome prediction is therefore essential in determining further therapeutic
      interventions. The electroencephalogram is a standardized and commonly available
      tool used to estimate prognosis in postanoxic patients. The identification of
      pathological EEG patterns with poor prognosis relies however primarily on visual
      EEG scoring by experts. We introduced a model-based approach of EEG analysis
      (state space model) that allows for an objective and quantitative description of
      spectral EEG variability. METHODS: We retrospectively analyzed standard EEG
      recordings in 83 comatose patients after cardiac arrest between 2005 and 2013 in
      the intensive care unit of the University Hospital Zurich. Neurological outcome
      was assessed one month after cardiac arrest using the Cerebral Performance
      Category. For a dynamic and quantitative EEG analysis, we implemented a model
      based approach (state space analysis) to quantify EEG background variability
      independent from visual scoring of EEG epochs. Spectral variability was compared
      between groups and correlated with clinical outcome parameters and visual EEG
      patterns. RESULTS: Quantitative assessment of spectral EEG variability (state
      space velocity) revealed significant differences between patients with poor and
      good outcome after cardiac arrest: Lower mean velocity in temporal electrodes (T4
      and T5) was significantly associated with poor prognostic outcome (p<0.005) and
      correlated with independently identified visual EEG patterns such as generalized
      periodic discharges (p<0.02). Receiver operating characteristic (ROC) analysis
      confirmed the predictive value of lower state space velocity for poor clinical
      outcome after cardiac arrest (AUC 80.8, 70% sensitivity, 15% false positive
      rate). CONCLUSION: Model-based quantitative EEG analysis (state space analysis)
      provides a novel, complementary marker for prognosis in postanoxic
      encephalopathy.

PMID- 28750885
TI  - Regional cerebral saturation monitoring during withdrawal of life support until
      death.
AB  - AIMS: The aim of this pilot study was to explore the regional cerebral oxygen
      saturation (rSO2) during the process of dying in Intensive Care Unit (ICU)
      patients in whom it was decided to withdraw life support. METHODS: Regional
      cerebral saturation was measured from the moment active treatment was stopped
      until the moment of death, defined as the onset of asystole. Simultaneously,
      heart rate and arterial blood pressure were recorded using a radial arterial
      catheter. Baseline rSO2 values were calculated as mean values over one hour in
      stable haemodynamic conditions immediately after the decision to withdraw life
      support. RESULTS: Cerebral saturation was measured in six dying ICU patients. The
      mean age of patients was 64year. The median baseline rSO2 value was 64% (58%
      68%). At time of death, median rSO2 was 33% (7%-40%). The median decrease in rSO2
      from baseline until death was 31% (25%-45%). The median decrease in rSO2 observed
      during the last hour before time of death was 20% (12%-31%). CONCLUSION: A
      continuous and patient specific decrease in rSO2 was observed in all patients
      with a simultaneous decrease in MAP. However, the absolute rSO2 value at moment
      death was clinically determined, had a broad range, indicating that there is no
      clear cut-off rSO2 value for death probably due to the heterogeneity of the
      studied population. Taken together, these observations highlight the importance
      of following trends and comparing rSO2 values in the cardiac arrest setting.

PMID- 28750886
TI  - Intubation is not a marker for coma after in-hospital cardiac arrest: A
      retrospective study.
AB  - INTRODUCTION: In-hospital cardiac arrest (IHCA) strikes over 200,000 people in
      the United States annually. Targeted temperature management (TTM) is considered
      beneficial in other settings, but there is no prospective data for IHCA. Recent
      work on TTM and IHCA found an association between TTM and worse outcome. However,
      the authors used intubation as a marker for coma to determine eligibility for
      TTM. The validity of this approach is unexplored. METHODS: Retrospective, single
      center study of adult patients with IHCA occurring in an intensive care unit,
      intubated prior to or during the event, or immediately after ROSC. We evaluated
      the percentage of patients documented as comatose after arrest, defined as
      Glasgow Comas Score (GCS) <8 for the primary analysis. We also evaluated the
      difference in hospital survival in patients with GCS <8 versus >=8. Two
      sensitivity analyses using different methods for defining coma using post-ROSC
      GCS were conducted. RESULTS: 29/102 (28%) intubated patients had a post-ROSC
      GCS>=8, and 22 (22%) were documented as following commands. Survival in patients
      with GCS>=8 vs.<8 was 62% (18/29) vs. 37% (27/73) in unadjusted analysis
      (p=0.02). The adjusted odds ratio for survival to hospital discharge was 3.81
      (95%CI: 1.37-10.61, p=0.01). Results were similar in both sensitivity analyses.
      CONCLUSIONS: Intubation prior to or during IHCA was not a valid marker of coma
      after ROSC. Post-ROSC mental status was associated with hospital survival, and
      thus could be an important confounder when conducting observational studies on
      the association of TTM with outcomes in this patient population.

PMID- 28750887
TI  - Probing the Interplay between Dendritic Spine Morphology and Membrane-Bound
      Diffusion.
AB  - Dendritic spines are protrusions along neuronal dendrites that harbor the
      majority of excitatory postsynapses. Their distinct morphology, often featuring a
      bulbous head and small neck that connects to the dendritic shaft, has been shown
      to facilitate compartmentalization of electrical and cytoplasmic signaling
      stimuli elicited at the synapse. The extent to which spine morphology also forms
      a barrier for membrane-bound diffusion has remained unclear. Recent simulations
      suggested that especially the diameter of the spine neck plays a limiting role in
      this process. Here, we examine the connection between spine morphology and
      membrane-bound diffusion through a combination of photoconversion, live-cell
      superresolution experiments, and numerical simulations. Local photoconversion was
      used to obtain the timescale of diffusive equilibration in spines and followed by
      global sparse photoconversion to determine spine morphologies with nanoscopic
      resolution. These morphologies were subsequently used to assess the role of
      morphology on the diffusive equilibration. From the simulations, we could
      determine a robust relation between the equilibration timescale and a generalized
      shape factor calculated using both spine neck width and neck length, as well as
      spine head size. Experimentally, we found that diffusive equilibration was often
      slower, but rarely faster than predicted from the simulations, indicating that
      other biological confounders further reduce membrane-bound diffusion in these
      spines. This shape-dependent membrane-bound diffusion in mature spines may
      contribute to spine-specific compartmentalization of neurotransmitter receptors
      and signaling molecules and thereby support long-term plasticity of synaptic
      contacts.

PMID- 28750888
TI  - The tumor suppressor CYLD controls epithelial morphogenesis and homeostasis by
      regulating mitotic spindle behavior and adherens junction assembly.
AB  - Epithelial morphogenesis and homeostasis are essential for animal development and
      tissue regeneration, and epithelial disorganization is associated with
      developmental disorders and tumorigenesis. However, the molecular mechanisms that
      contribute to the morphogenesis and homeostasis of the epithelium remain elusive.
      Herein, we report a novel role for the cylindromatosis (CYLD) tumor suppressor in
      these events. Our results show that CYLD depletion disrupts epithelial
      organization in both Drosophila egg chambers and mouse skin and intestinal
      epithelia. Microscopic analysis of proliferating cells in mouse epithelial
      tissues and cultured organoids reveals that loss of CYLD synergizes with tumor
      promoting agents to cause the misorientation of the mitotic spindle. Mechanistic
      studies show that CYLD accumulates at the cell cortex in epithelial tissues and
      cultured cells, where it promotes the formation of epithelial adherens junctions
      through the modulation of microtubule dynamics. These data suggest that CYLD
      controls epithelial morphogenesis and homeostasis by modulating the assembly of
      adherens junctions and ensuring proper orientation of the mitotic spindle. Our
      findings thus provide novel insight into the role of CYLD in development, tissue
      homeostasis, and tumorigenesis.

PMID- 28750889
TI  - Reciprocal activation of alpha5-nAChR and STAT3 in nicotine-induced human lung
      cancer cell proliferation.
AB  - Cigarette smoking is the top environmental risk factor for lung cancer. Nicotine,
      the addictive component of cigarettes, induces lung cancer cell proliferation,
      invasion and migration via the activation of nicotinic acetylcholine receptors
      (nAChRs). Genome-wide association studies (GWAS) show that CHRNA5 gene encoding
      alpha5-nAChR is especially relevant to lung cancer. However, the mechanism of
      this subunit in lung cancer is not clear. In the present study, we demonstrate
      that the expression of alpha5-nAChR is correlated with phosphorylated STAT3
      (pSTAT3) expression, smoking history and lower survival of non-small cell lung
      cancer (NSCLC) samples. Nicotine increased the levels of alpha5-nAChR mRNA and
      protein in NSCLC cell lines and activated the JAK2/STAT3 signaling cascade.
      Nicotine-induced activation of JAK2/STAT3 signaling was inhibited by the
      silencing of alpha5-nAChR. Characterization of the CHRNA5 promoter revealed four
      STAT3-response elements. ChIP assays confirmed that the CHRNA5 promoter contains
      STAT3 binding sites. By silencing STAT3 expression, nicotine-induced upregulation
      of alpha5-nAChR was suppressed. Downregulation of alpha5-nAChR and/or STAT3
      expression inhibited nicotine-induced lung cancer cell proliferation. These
      results suggest that there is a feedback loop between alpha5-nAChR and STAT3 that
      contributes to the nicotine-induced tumor cell proliferation, which indicates
      that alpha5-nAChR is an important therapeutic target involved in tobacco
      associated lung carcinogenesis.

PMID- 28750890
TI  - Cost analysis of substitutive renal therapies in children.
AB  - OBJECTIVE: End-stage renal disease is a health problem that consumes public and
      private resources. This study aimed to identify the cost of hemodialysis (either
      daily or conventional hemodialysis) and transplantation in children and
      adolescents. METHODS: This was a retrospective cohort of pediatric patients with
      End-stage renal disease who underwent hemodialysis followed by kidney transplant.
      All costs incurred in the treatment were collected and the monthly total cost was
      calculated per patient and for each renal therapy. Subsequently, a dynamic panel
      data model was estimated. RESULTS: The study included 30 children who underwent
      hemodialysis (16 conventional/14 daily hemodialysis) followed by renal
      transplantation. The mean monthly outlay for hemodialysis was USD 3500 and USD
      1900 for transplant. Hemodialysis costs added up to over USD 87,000 in 40 months
      for conventional dialysis patients and USD 131,000 in 50 months for daily
      dialysis patients. In turn, transplant costs in 50 months reached USD 48,000 and
      USD 70,000, for conventional and daily dialysis patients, respectively. For
      conventional dialysis patients, transplant is less costly when therapy exceeds 16
      months, whereas for daily dialysis patients, the threshold is around 13 months.
      CONCLUSION: Transplantation is less expensive than dialysis in children, and the
      estimated thresholds indicate that renal transplant should be the preferred
      treatment for pediatric patients.

PMID- 28750891
TI  - Triaging the Emergency Department, Not the Patient: United States Emergency
      Nurses' Experience of the Triage Process.
AB  - INTRODUCTION: Triage, as it is understood in the context of the emergency
      department, is the first and perhaps the most formal stage of the initial patient
      encounter. Bottlenecks during intake and long waiting room times have been linked
      to higher rates of patients leaving without being seen. The solution in many
      emergency departments has been to collect less information at triage or use an
      "immediate bedding" or "pull until full" approach, in which patients are placed
      in treatment areas as they become available without previous screening. The
      purpose of this study was to explore emergency nurses' understanding of-and
      experience with-the triage process, and to identify facilitators and barriers to
      accurate acuity assignation. METHODS: An exploratory qualitative study using
      focus-group interviews (N = 26). RESULTS: Five themes were identified: (1) "Sick
      or not sick," (2) "Competency/qualifications," (3) "Triaging the emergency
      department, not the patient," (4) "The unexpected," and (5) "Barriers and
      facilitators." DISCUSSION: Our participants described processes that were unit-
      and/or nurse-dependent and were manipulations of the triage system to "fix"
      problems in ED flow, rather than a standard application of a triage system. Our
      participants reported that, in practice, the use of triage scales to determine
      acuity and route patients to appropriate resources varies in accuracy and
      application among emergency nurses and in their respective emergency departments.
      Nurses in this sample reported a prevalence of "quick look" triage approaches
      that do not rely on physiologic data to make acuity decisions. Future research
      should focus on intervention and comparison studies examining the effect of
      staffing, nurse experience, hospital policies, and length of shift on the
      accuracy of triage decision making. Contribution to Emergency Nursing Practice.

PMID- 28750892
TI  - Getting poetic with data: Using poetry to disseminate the first-person voices of
      parents of children with a disability.
AB  - OBJECTIVE: This paper considers the limitations of traditional prose-based
      approaches to research dissemination and explores the potential merits and
      tensions in adopting a poetic approach to disseminate participants' experiences
      and perspectives. DISCUSSION: Drawing on our experience of using I-poetry to
      create first-person poems from our research data we discuss the attractiveness of
      the subjective, expressive and relational opportunities of poetry, and its
      ability to compress experience and create emotional connections and evoke
      emotion. We also reflect upon and discuss the limitations, challenges and
      criticisms of the use of research poetry, with a specific focus on the use of
      data poems and their value in disseminating research findings. CONCLUSION: Using
      poetry compelled us to think with our data differently and our poems have
      generated visceral responses from parents and professionals. Research poetry has
      value within academic and clinical worlds but its greatest potential perhaps lies
      in providing a means of disseminating research to the wider range of
      stakeholders.

PMID- 28750893
TI  - Early pediatric formulation development with new chemical entities: Opportunities
      of e-tongue besides human taste assessment.
AB  - The palatability of a pediatric drug formulation is one of the key prerequisites
      for therapeutic success. Liquid formulations are often chosen for pediatric drug
      products, and they require special attention regarding their taste, as they have
      direct contact to the taste buds and a relatively long residence time in the oral
      cavity. For ethical reasons, the role of electronic tongues in the development of
      oral drug formulations with new chemical entities (NCEs) for pediatric use is
      growing, however, little is known about the strategies how this instrumental
      taste assessment can be performed. The present study illustrates two
      possibilities to combine in-vitro and in-vivo data for the characterization of
      the palatability of the new drug candidates CSE3104 and CSE3165. As a first step,
      the implementation and suitability of electronic tongue measurements has been
      demonstrated by comparison of in-vivo and in-vitro data. In alignment with the
      taste assessment results during a single-center, double-blinded, randomized,
      placebo-controlled, single ascending dose (SAD) study in healthy subjects, the
      bitter taste perception of CSE3104 was assessed with e-tongue measurements.
      Moreover, the sensor response pattern showed comparable results of the e-tongue
      measurements to the human taste study of CSE3165: With increasing concentration,
      the bitterness values were increased. In addition, the human taste pattern showed
      increasing values for sourness due to higher volumes of the citric acid buffer.
      Results of the hedonic descriptor "unpleasant" within the human taste assessments
      could be related to bitterness in the instrumental taste assessment. For the
      second step in electronic tongue guided formulation development two possibilities
      are depicted in the article focusing on the effect of different excipients on the
      formulation on the one hand and on the assessment and comparison of two drug
      formulations on the other hand. Based on these results, the low number of healthy
      volunteers for the taste assessment in a Phase 1 study led to a meaningful
      interpretation, by applying in addition the electronic tongue. Using this
      instrumental approach led to reproducible data versus the human taste assessment,
      without ethical concerns, and with a reduction in time and costs.

PMID- 28750894
TI  - Patient acceptability of 3D printed medicines.
AB  - Patient-centric medicine is a derivative term for personalised medicine, whereby
      the pharmaceutical product provides the best overall benefit by meeting the
      comprehensive needs of the individual; considering the end-user from the
      beginning of the formulation design process right through development to an end
      product is a must. One way in which to obtain personalised medicines, on-site and
      on-demand is by three-dimensional printing (3DP). The aim of this study was to
      investigate the influence of the shape, size and colour of different placebo 3D
      printed tablets (PrintletsTM) manufactured by fused deposition modelling (FDM)
      3DP on end-user acceptability regarding picking and swallowing. Ten different
      printlet shapes were prepared by 3DP for an open-label, randomised, exploratory
      pilot study with 50 participants. Participant-reported outcome (PRO) and
      researcher reported outcome (RRO) were collected after picking and swallowing of
      selected printlet geometries including sphere, torus, disc, capsule and tilted
      diamond shapes. The torus printlet received the highest PRO cores for ease of
      swallowing and ease of picking. Printlets with a similar appearance to
      conventional formulations (capsule and disc shape) were also found to be easy to
      swallow and pick which demonstrates that familiarity is a critical acceptability
      attribute for end-users. RRO scores were in agreement with the PRO scores. The
      sphere was not perceived to be an appropriate way of administering an oral solid
      medicine. Smaller printlet sizes were found to be preferable; however it was
      found that the perception of size was driven by the type of shape. Printlet
      colour was also found to affect the perception of the end-user. Our study is the
      first to guide the pharmaceutical industry towards developing patient-centric
      medicine in different geometries via 3DP. Overall, the highest acceptability
      scores for torus printlets indicates that FDM 3DP is a promising fabrication
      technology towards increasing patient acceptability of solid oral medicines.

PMID- 28750895
TI  - Genotoxic evaluation of poly(anhydride) nanoparticles in the gastrointestinal
      tract of mice.
AB  - Gantrez(r) AN 119-based NPs have been developed as oral drug carriers due to
      their strong bioadhesive interaction with components of the gastrointestinal
      mucosa and to their adaptable surface. The use of mannosamine to coat Gantrez(r)
      AN 119-based NPs results in a high mucus-permeable carrier, able to reach the
      gastrointestinal epithelium. Although their efficacy to transport a therapeutic
      agent has been demonstrated, their safety has not yet been thoroughly studied.
      They have proved to be non-cytotoxic, non-genotoxic and non-mutagenic in vitro;
      however, the in vivo toxicity profile has not yet been determined. In this study,
      the in vivo genotoxic potential of Gantrez(r) AN 119 NPs coated with mannosamine
      (GN-MA-NP) has been assessed using the in vivo comet assay in combination with
      the enzyme formamidopyrimidine DNA glycosylase in mice, following the OECD test
      guideline 489. To determine the relevant organs to analyse and the sampling
      times, an in vivo biodistribution study was also carried out. Results showed a
      statistically significant induction of DNA strand breaks and oxidized bases in
      the duodenum of animals exposed to 2000 mg/kg bw. However, this effect was not
      observed at lower doses (i.e. 500 and 1000 mg/kg which are closer to the
      potential therapeutic doses) or in other organs. In conclusion, GN-MA-NP are
      promising nanocarriers as oral drug delivery systems.

PMID- 28750896
TI  - A novel mechanical antrum model for the prediction of the gastroretentive
      potential of dosage forms.
AB  - The development of gastroretentive dosage forms can be significantly enhanced by
      the reliable estimation of gastroretentive properties in vitro. In this context,
      it is mandatory to consider the propulsive contraction waves that occur in the
      antral region of the stomach, since they are regarded as the major physiological
      hurdle to overcome. Therefore, the aim of this study was to develop an in vitro
      model that allowed the evaluation of the gastroretentive potential of objects
      with different properties (e.g. size, shape and elasticity). The model enabled a
      realistic simulation of the human antrum and occurring contraction waves. We
      could demonstrate that larger objects made of elastic polyurethane foam were more
      rapidly emptied by the model than smaller objects having the same shape. Compared
      to this, rigid as well as slippery objects showed decreased gastroretentive
      properties. In contrast, a self-formed trichobezoar - an indigestible object
      known to remain in the stomach - showed the highest gastroretentive potential. We
      suggest that the gastroretentive potential of objects of a certain size increases
      if they exhibit compressible and elastic properties along with certain
      dimensions. The data showed that the development of novel gastroretentive dosage
      forms may be facilitated with the aid of the mechanical antrum model.

PMID- 28750897
TI  - Inhibition of Clostridium perfringens epsilon toxin by beta-cyclodextrin
      derivatives.
AB  - Clostridium perfringens epsilon toxin (ETX) is considered as one of the most
      dangerous potential biological weapons. The goal of this work was to identify
      inhibitors of ETX using a novel approach for the inactivation of pore-forming
      toxins. The approach is based on the blocking of the target pore with molecules
      having the same symmetry as the pore itself. About 200 various beta-cyclodextrin
      derivatives were screened for inhibitors of ETX activity using a colorimetric
      cell viability assay. Several compounds with dose-dependent activities at low
      micromolar concentrations have been identified. The same compounds were also able
      to inhibit lethal toxin of Bacillus anthracis.

PMID- 28750898
TI  - The use of a unique co-culture model of fetoplacental steroidogenesis as a
      screening tool for endocrine disruptors: The effects of neonicotinoids on
      aromatase activity and hormone production.
AB  - Estrogen biosynthesis during pregnancy is dependent on the collaboration between
      the fetus producing the androgen precursors, and the placenta expressing the
      enzyme aromatase (CYP19). Disruption of estrogen production by contaminants may
      result in serious pregnancy outcomes. We used our recently developed in vitro co
      culture model of fetoplacental steroidogenesis to screen the effects of three
      neonicotinoid insecticides on the catalytic activity of aromatase and the
      production of steroid hormones. A co-culture of H295R human adrenocortical
      carcinoma cells with fetal characteristics and BeWo human choriocarcinoma cells
      which display characteristics of the villous cytotrophoblast was exposed for 24h
      to various concentrations of three neonicotinoids: thiacloprid, thiamethoxam and
      imidacloprid. Aromatase catalytic activity was determined in both cell lines
      using the tritiated water-release assay. Hormone production was measured by
      ELISA. The three neonicotinoids induced aromatase activity in our fetoplacental
      co-culture and concordingly, estradiol and estrone production were increased. In
      contrast, estriol production was strongly inhibited by the neonicotinoids. All
      three pesticides induced the expression of CYP3A7 in H295R cells, and this
      induction was reversed by co-treatment of H295R cells with exogenous estriol.
      CYP3A7 is normally expressed in fetal liver and is a key enzyme involved in
      estriol synthesis. We suggest that neonicotinoids are metabolized by CYP3A7, thus
      impeding the 16alpha-hydroxylation of fetal DHEA(-sulfate), which is normally
      converted to estriol by placental aromatase. We successfully used the
      fetoplacental co-culture as a physiologically relevant tool to highlight the
      potential effects of neonicotinoids on estrogen production, aromatase activity
      and CYP3A7 expression during pregnancy.

PMID- 28750899
TI  - Evaluation of the frequency of food allergens based on skin prick test in
      children in Kurdistan Province - Iran.
AB  - INTRODUCTION: Food allergy refers to abnormal reactions of the body caused by an
      immune system response to food. This study was conducted aiming to investigate
      allergy to food allergens in children with food allergies. MATERIALS AND METHODS:
      This study was conducted as a cross-sectional one on 304 children aged six months
      to seven years with food allergies admitted to the tertiary referral hospital in
      Kurdistan Province - Iran, during 2014-2015. All the patients were examined for
      skin prick test using 49 allergens. Finally, the obtained data were analysed
      using SPSS15 and chi-square and t tests. RESULTS: The highest percentage of
      occurrence of bump reaction (wheal) and redness (flare) was due to the
      consumption of fish, eggs, tomatoes, and cocoa. Moreover, the lowest rate of
      wheal and flare was caused by exposure to allergens like latex, tea, malt, and
      wheat flour. The reaction most created due to the consumption of foods was flare
      which was higher among under three-year-olds group (p<0.05), and between the
      sexes, girls showed the most common allergic reactions (p<0.05). CONCLUSION:
      Since food allergy has a high prevalence in children, it should be considered
      with great interest. Considering that avoiding food allergens is the first step
      in the treatment of food allergies, the present study may be a useful guide in
      this regard.

PMID- 28750900
TI  - Virulence of an H5N8 highly pathogenic avian influenza is enhanced by the amino
      acid substitutions PB2 E627K and HA A149V.
AB  - A novel reassortant H5N8 highly pathogenic avian influenza (HPAI) virus was
      recently identified in Asia, Europe, and North America. The H5N8 HPAI virus has
      raised serious concerns regarding the potential risk for human infection.
      However, the molecular changes responsible for allowing mammalian infection in
      H5N8 HPAI viruses are not clear. The objective of this study was to identify
      amino acid substitutions that are potentially associated with the adaptation of
      H5N8 HPAI viruses to mammals. In this study, an avian-origin H5N8 virus was
      adapted to mice through serial lung-to-lung passage. The virulence of mouse
      adapted virus was increased and adaptive mutations, HA (A149V) and PB2 (E627K),
      were detected after the ninth passage in each series of mice. Reverse genetics
      were used to generate reassortants of the wild type and mouse-adapted viruses.
      Substitutions in the HA (A149V) and PB2 (E627K) proteins led to enhanced viral
      virulence in mice, the viruses displayed expanded tissue tropism, and increased
      replication kinetics in mammalian cells. Continued surveillance in poultry for
      amino acid changes that might indicate H5N8 HPAI viruses pose a threat to human
      health is required.

PMID- 28750901
TI  - Complex reassortment events of unusual G9P[4] rotavirus strains in India between
      2011 and 2013.
AB  - Rotavirus A (RVA) is the predominant etiological agent of acute gastroenteritis
      in young children worldwide. Recently, unusual G9P[4] rotavirus strains emerged
      with high prevalence in many countries. Such intergenogroup reassortant strains
      highlight the ongoing spread of unusual rotavirus strains throughout Asia. This
      study was undertaken to determine the whole genome of eleven unusual G9P[4]
      strains detected in India during 2011-2013, and to compare them with other human
      and animal global RVAs to understand the exact origin of unusual G9P[4]
      circulating in India and other countries worldwide. Of these 11 RVAs, four G9P[4]
      strains were double-reassortants with the G9-VP7 and E6-NSP4 genes on a DS-1-like
      genetic backbone (G9-P[4]-I2-R2-C2-M2-A2-N2-T2-E6-H2). The other strains showed a
      complex genetic constellation, likely derived from triple reassortment event with
      the G9-VP7, N1-NSP2 and E6-NSP4 on a DS-1-like genetic backbone (G9-P[4]-I2-R2-C2
      M2-A2-N1-T2-E6-H2). Presumably, these unusual G9P[4] strains were generated after
      several reassortment events between the contemporary co-circulating human
      rotavirus strains. Moreover, the point mutation S291L at the interaction site
      between inner and outer capsid proteins of VP6 gene may be important in the rapid
      spread of this unusual strain. The complex reassortment events within the G9[4]
      strains may be related to the high prevalence of mixed infections in India as
      reported in this study and other previous studies.

PMID- 28750902
TI  - Adaptable pattern recognition system for discriminating Melanocytic Nevi from
      Malignant Melanomas using plain photography images from different image
      databases.
AB  - OBJECTIVE: The aim of this study was to propose features that evaluate pictorial
      differences between melanocytic nevus (mole) and melanoma lesions by computer
      based analysis of plain photography images and to design a cross-platform,
      tunable, decision support system to discriminate with high accuracy moles from
      melanomas in different publicly available image databases. MATERIAL AND METHODS:
      Digital plain photography images of verified mole and melanoma lesions were
      downloaded from (i) Edinburgh University Hospital, UK, (Dermofit, 330moles/70
      melanomas, under signed agreement), from 5 different centers (Multicenter,
      63moles/25 melanomas, publicly available), and from the Groningen University,
      Netherlands (Groningen, 100moles/70 melanomas, publicly available). Images were
      processed for outlining the lesion-border and isolating the lesion from the
      surrounding background. Fourteen features were generated from each lesion
      evaluating texture (4), structure (5), shape (4) and color (1). Features were
      subjected to statistical analysis for determining differences in pictorial
      properties between moles and melanomas. The Probabilistic Neural Network (PNN)
      classifier, the exhaustive search features selection, the leave-one-out (LOO),
      and the external cross-validation (ECV) methods were used to design the PR-system
      for discriminating between moles and melanomas. RESULTS: Statistical analysis
      revealed that melanomas as compared to moles were of lower intensity, of less
      homogenous surface, had more dark pixels with intensities spanning larger spectra
      of gray-values, contained more objects of different sizes and gray-levels, had
      more asymmetrical shapes and irregular outlines, had abrupt intensity transitions
      from lesion to background tissue, and had more distinct colors. The PR-system
      designed by the Dermofit images scored on the Dermofit images, using the ECV,
      94.1%, 82.9%, 96.5% for overall accuracy, sensitivity, specificity, on the
      Multicenter Images 92.0%, 88%, 93.7% and on the Groningen Images 76.2%, 73.9%,
      77.8% respectively. CONCLUSION: The PR-system as designed by the Dermofit image
      database could be fine-tuned to classify with good accuracy plain photography
      moles/melanomas images of other databases employing different image capturing
      equipment and protocols.

PMID- 28750903
TI  - Computing eye gaze metrics for the automatic assessment of radiographer
      performance during X-ray image interpretation.
AB  - AIM: To investigate image interpretation performance by diagnostic radiography
      students, diagnostic radiographers and reporting radiographers by computing eye
      gaze metrics using eye tracking technology. METHODS: Three groups of participants
      were studied during their interpretation of 8 digital radiographic images
      including the axial and appendicular skeleton, and chest (prevalence of normal
      images was 12.5%). A total of 464 image interpretations were collected.
      Participants consisted of 21 radiography students, 19 qualified radiographers and
      18 qualified reporting radiographers who were further qualified to report on the
      musculoskeletal (MSK) system. OUTCOME MEASURES: Eye tracking data was collected
      using the Tobii X60 eye tracker and subsequently eye gaze metrics were computed.
      Voice recordings, confidence levels and diagnoses provided a clear demonstration
      of the image interpretation and the cognitive processes undertaken by each
      participant. A questionnaire afforded the participants an opportunity to offer
      information on their experience in image interpretation and their opinion on the
      eye tracking technology. RESULTS: Reporting radiographers demonstrated a 15%
      greater accuracy rate (p<=0.001), were more confident (p<=0.001) and took a mean
      of 2.4s longer to clinically decide on all features compared to students.
      Reporting radiographers also had a 15% greater accuracy rate (p<=0.001), were
      more confident (p<=0.001) and took longer to clinically decide on an image
      diagnosis (p=0.02) than radiographers. Reporting radiographers had a greater mean
      fixation duration (p=0.01), mean fixation count (p=0.04) and mean visit count
      (p=0.04) within the areas of pathology compared to students. Eye tracking
      patterns, presented within heat maps, were a good reflection of group expertise
      and search strategies. Eye gaze metrics such as time to first fixate, fixation
      count, fixation duration and visit count within the areas of pathology were
      indicative of the radiographer's competency. CONCLUSION: The accuracy and
      confidence of each group could be reflected in the variability of their eye
      tracking heat maps. Participants' thoughts and decisions were quantified using
      the eye tracking data. Eye tracking metrics also reflected the different search
      strategies that each group of participants adopted during their image
      interpretations. This is the first study to use eye tracking technology to assess
      image interpretation skills between various groups of different levels of
      experience in radiography, especially on a combination of the MSK system, chest
      cavity and a variety of pathologies.

PMID- 28750905
TI  - Automated problem list generation and physicians perspective from a pilot study.
AB  - OBJECTIVE: An accurate, comprehensive and up-to-date problem list can help
      clinicians provide patient-centered care. Unfortunately, problem lists created
      and maintained in electronic health records by providers tend to be inaccurate,
      duplicative and out of date. With advances in machine learning and natural
      language processing, it is possible to automatically generate a problem list from
      the data in the EHR and keep it current. In this paper, we describe an automated
      problem list generation method and report on insights from a pilot study of
      physicians' assessment of the generated problem lists compared to existing
      providers-curated problem lists in an institution's EHR system. MATERIALS AND
      METHODS: The natural language processing and machine learning-based Watson1
      method models clinical thinking in identifying a patient's problem list using
      clinical notes and structured data. This pilot study assessed the Watson method
      and included 15 randomly selected, de-identified patient records from a large
      healthcare system that were each planned to be reviewed by at least two internal
      medicine physicians. The physicians created their own problem lists, and then
      evaluated the overall usefulness of their own problem lists (P), Watson generated
      problem lists (W), and the existing EHR problem lists (E) on a 10-point scale.
      The primary outcome was pairwise comparisons of P, W, and E. RESULTS: Six out of
      the 10 invited physicians completed 27 assessments of P, W, and E, and in process
      evaluated 732 Watson generated problems and 444 problems in the EHR system. As
      expected, physicians rated their own lists, P, highest. However, W was rated
      higher than E. Among 89% of assessments, Watson identified at least one important
      problem that physicians missed. CONCLUSION: Cognitive computing systems like this
      Watson system hold the potential for accurate, problem-list-centered
      summarization of patient records, potentially leading to increased efficiency,
      better clinical decision support, and improved quality of patient care.

PMID- 28750904
TI  - A comparison of rule-based and machine learning approaches for classifying
      patient portal messages.
AB  - OBJECTIVE: Secure messaging through patient portals is an increasingly popular
      way that consumers interact with healthcare providers. The increasing burden of
      secure messaging can affect clinic staffing and workflows. Manual management of
      portal messages is costly and time consuming. Automated classification of portal
      messages could potentially expedite message triage and delivery of care.
      MATERIALS AND METHODS: We developed automated patient portal message classifiers
      with rule-based and machine learning techniques using bag of words and natural
      language processing (NLP) approaches. To evaluate classifier performance, we used
      a gold standard of 3253 portal messages manually categorized using a taxonomy of
      communication types (i.e., main categories of informational, medical, logistical,
      social, and other communications, and subcategories including prescriptions,
      appointments, problems, tests, follow-up, contact information, and
      acknowledgement). We evaluated our classifiers' accuracies in identifying
      individual communication types within portal messages with area under the
      receiver-operator curve (AUC). Portal messages often contain more than one type
      of communication. To predict all communication types within single messages, we
      used the Jaccard Index. We extracted the variables of importance for the random
      forest classifiers. RESULTS: The best performing approaches to classification for
      the major communication types were: logistic regression for medical
      communications (AUC: 0.899); basic (rule-based) for informational communications
      (AUC: 0.842); and random forests for social communications and logistical
      communications (AUCs: 0.875 and 0.925, respectively). The best performing
      classification approach of classifiers for individual communication subtypes was
      random forests for Logistical-Contact Information (AUC: 0.963). The Jaccard
      Indices by approach were: basic classifier, Jaccard Index: 0.674; Naive Bayes,
      Jaccard Index: 0.799; random forests, Jaccard Index: 0.859; and logistic
      regression, Jaccard Index: 0.861. For medical communications, the most predictive
      variables were NLP concepts (e.g., Temporal_Concept, which maps to 'morning',
      'evening' and Idea_or_Concept which maps to 'appointment' and 'refill'). For
      logistical communications, the most predictive variables contained similar
      numbers of NLP variables and words (e.g., Telephone mapping to 'phone',
      'insurance'). For social and informational communications, the most predictive
      variables were words (e.g., social: 'thanks', 'much', informational: 'question',
      'mean'). CONCLUSIONS: This study applies automated classification methods to the
      content of patient portal messages and evaluates the application of NLP
      techniques on consumer communications in patient portal messages. We demonstrated
      that random forest and logistic regression approaches accurately classified the
      content of portal messages, although the best approach to classification varied
      by communication type. Words were the most predictive variables for
      classification of most communication types, although NLP variables were most
      predictive for medical communication types. As adoption of patient portals
      increases, automated techniques could assist in understanding and managing
      growing volumes of messages. Further work is needed to improve classification
      performance to potentially support message triage and answering.

PMID- 28750906
TI  - Quantitative metrics for evaluating the phased roll-out of clinical information
      systems.
AB  - OBJECTIVES: We introduce a novel quantitative approach for evaluating the order
      of roll-out during phased introduction of clinical information systems. Such roll
      outs are associated with unavoidable risk due to patients transferring between
      clinical areas using both the old and new systems. METHODS: We proposed a simple
      graphical model of patient flow through a hospital. Using a simple instance of
      the model, we showed how a roll-out order can be generated by minimising the flow
      of patients from the new system to the old system. RESULTS: The model was applied
      to admission and discharge data acquired from 37,080 patient journeys at the
      Churchill Hospital, Oxford between April 2013 and April 2014. The resulting order
      was evaluated empirically and produced acceptable orders. DISCUSSION: The
      development of data-driven approaches to clinical Information system roll-out
      provides insights that may not necessarily be ascertained through clinical
      judgment alone. Such methods could make a significant contribution to the smooth
      running of an organisation during the roll-out of a potentially disruptive
      technology. CONCLUSION: Unlike previous approaches, which are based on clinical
      opinion, the approach described here quantitatively assesses the appropriateness
      of competing roll-out strategies. The data-driven approach was shown to produce
      strategies that matched clinical intuition and provides a flexible framework that
      may be used to plan and monitor Clinical Information System roll-out.

PMID- 28750907
TI  - Barriers to technology use among older heart failure individuals in managing
      their symptoms after hospital discharge.
AB  - BACKGROUND: In North America, heart failure (HF) is the leading cause for
      hospital readmission. Supportive technology, such as computers and tablets, could
      potentially assist patients with self-care to manage their condition after
      hospital discharge; however, older individuals have difficulties in adopting
      technology to manage their condition. METHOD: This study used a mixed methods
      design to identify barriers to technology use in HF self-care. In the qualitative
      phase, semi-structured interviews were conducted with 18 HF patients and 10
      informal caregivers or care partners (CP). In the quantitative phase, five
      questionnaires were administered to 15 patients and 8 CP: Montreal Cognitive
      Assessment; Short Literacy Survey and Subjective Numeracy Scale; Self-Care of HF
      Index; Knowledge Assessment Questionnaire; and Patient Activation Measure.
      RESULTS: In the qualitative phase, five themes emerged regarding engagement in
      self care and technology use: knowledge level of HF; level of willingness to ask
      questions related to HF; confidence level in making health-related decisions
      individually; level of technology usage in daily activities; and self-recording
      of health measurements. Quantitative analysis found that most HF patients had
      mild cognitive impairment (MCI), adequate health numeracy levels to understand
      and manage their health condition, high confidence levels in managing their
      condition and willingness to engage in self-care. There was variation in
      willingness to adopt technology. CONCLUSION: Patients were willing to engage in
      HF self-care however they relied on CPs who were more willing to ask questions
      about HF. Technology tools may assist in HF self-care, but they must be tailored
      for use among older individuals.

PMID- 28750908
TI  - A systematic review of the effectiveness of interruptive medication prescribing
      alerts in hospital CPOE systems to change prescriber behavior and improve patient
      safety.
AB  - OBJECTIVES: To assess the evidence of the effectiveness of different categories
      of interruptive medication prescribing alerts to change prescriber behavior
      and/or improve patient outcomes in hospital computerized provider order entry
      (CPOE) systems. METHODS: PubMed, Embase, CINAHL and the Cochrane Library were
      searched for relevant articles published between January 2000 and February 2016.
      Studies were included if they compared the outcomes of automatic, interruptive
      medication prescribing alert/s to a control/comparison group to determine alert
      effectiveness. RESULTS: Twenty-three studies describing 32 alerts classified into
      11 alert categories were identified. The most common alert categories studied
      were drug-condition interaction (n=6), drug-drug interaction alerts (n=6) and
      corollary order alerts (n=6). All 23 papers investigated the effect of the
      intervention alert on at least one outcome measure of prescriber behavior. Just
      over half of the studies (53%, n=17) reported a statistically significant
      beneficial effect from the intervention alert; 34% (n=11) reported no
      statistically significant effect, and 6% (n=2) reported a significant detrimental
      effect. Two studies also evaluated the effect of alerts on patient outcome
      measures; neither finding that patient outcomes significantly improved following
      alert implementation (6%, n=2). The greatest volume of evidence relates to three
      alert categories: drug-condition, drug-drug and corollary order alerts. Of these,
      drug-condition alerts had the greatest number of studies reporting positive
      effects (five out of six studies). Only two of six studies of drug-drug
      interaction and one of six of corollary alerts reported positive benefits.
      DISCUSSION AND CONCLUSION: The current evidence-base does not show a clear
      indication that particular categories of alerts are more effective than others.
      While the majority of alert categories were shown to improve outcomes in some
      studies, there were also many cases where outcomes did not improve. This lack of
      evidence hinders decisions about the amount and type of decision support that
      should be integrated into CPOE systems to increase safety while reducing the risk
      of alert fatigue. Virtually no studies have sought to investigate the impact on
      changes to prescriber behavior and outcomes overall when alerts from multiple
      categories are incorporated within the same system.

PMID- 28750909
TI  - Thank you for asking: Exploring patient perceptions of barcode medication
      administration identification practices in inpatient mental health settings.
AB  - BACKGROUND: Barcode medication administration systems have been implemented in a
      number of healthcare settings in an effort to decrease medication errors. To use
      the technology, nurses are required to login to an electronic health record, scan
      a medication and a form of patient identification to ensure that these correspond
      correctly with the ordered medications prior to medication administration. In
      acute care settings, patient wristbands have been traditionally used as a form of
      identification; however, past research has suggested that this method of
      identification may not be preferred in inpatient mental health settings. If
      barcode medication administration technology is to be effectively used in this
      context, healthcare organizations need to understand patient preferences with
      regards to identification methods. PURPOSE: The purpose of this study was to
      elicit patient perceptions of barcode medication administration identification
      practices in inpatient mental health settings. Insights gathered can be used to
      determine patient-centered preferences of identifying patients using barcode
      medication administration technology. METHODS: Using a qualitative descriptive
      approach, fifty-two (n=52) inpatient interviews were completed by a Peer Support
      Worker using a semi-structured interview guide over a period of two months.
      Interviews were conducted in a number of inpatient mental health areas including
      forensic, youth, geriatric, acute, and rehabilitation services. An
      interprofessional team, inclusive of a Peer Support Worker, completed a thematic
      analysis of the interview data. RESULTS: Six themes emerged as a result of the
      inductive data analysis. These included: management of information, privacy and
      security, stigma, relationships, safety and comfort, and negative associations
      with the technology. Patients also indicated that they would like a choice in the
      type of identification method used during barcode medication administration. As
      well, suggestions were made for how barcode medication administration practices
      could be modified to become more patient-centered. CONCLUSION: The results of
      this study have a number of implications for healthcare organizations. As
      patients indicated that they would like a choice in the type of identification
      method used during barcode medication administration, healthcare organizations
      will need to determine how they can facilitate this process. Furthermore, many of
      the concerns that patients had with barcode medication administration technology
      could be addressed through patient education.

PMID- 28750910
TI  - Click yes to consent: Acceptability of incorporating informed consent into an
      internet-based testing program for sexually transmitted and blood-borne
      infections.
AB  - BACKGROUND: Autonomous use of online health care services without interaction
      with a health care provider challenges existing models for achieving informed
      consent (IC); current examinations of this issue have focused on commercial
      direct-to-consumer genetic testing. As IC is integral to publicly funded clinical
      testing services, we incorporated pre-test concepts necessary for IC in
      GetCheckedOnline (GCO), British Columbia's online sexually transmitted and blood
      borne infection (STBBI) testing service. OBJECTIVE: We assessed the acceptability
      of this IC step and its design options among potential users during usability
      testing of GCO. METHODS: English-speaking participants>=19years were recruited
      from Craigslist and among provincial STI clinic clients for usability testing of
      an early version of GCO, which included a consent webpage presenting 8 pre-test
      statements for review prior to completing testing. Participants were interviewed
      regarding their acceptability, perceptions, and understanding of the consent
      page; transcripts were analyzed thematically. RESULTS: We conducted 13 interviews
      (9 males, 4 females; 9 self-identified as heterosexual; all had previously tested
      for STBBI). We identified three main themes: i) the meaning of IC (consent page
      viewed as important and for protection of individual and organization;
      participants demonstrated varying understandings of specific components); ii) the
      impact of previous experience on understanding IC (participants understood
      difference between online and in-person testing; IC concepts were better
      understood by participants with more testing experience); iii) the role of
      website design on achieving IC (design of page to disrupt speedy click-throughs
      was valued and demonstrated seriousness of the consent page). CONCLUSIONS: Our
      careful attention to both content and design of the consent page of GCO was
      highly valued by potential users of the service, and effective in disrupting
      routinization of consent on websites. We argue that principles of IC apply
      equally in online self-testing programs as in clinical practice, and can be
      effectively achieved without detracting from the user experience.

PMID- 28750911
TI  - Technology meets tradition: The perceived impact of the introduction of
      information and communication technology on ward rounds in the intensive care
      unit.
AB  - BACKGROUND: Public policy in many health systems is currently dominated by the
      quest to find ways to 'do more with less'-to achieve better outcomes at a reduced
      cost. The success or failure of initiatives in support of this quest are often
      understood in terms of an adversarial dynamic or struggle between the
      professional logics of medicine and of management. Here, we use the case of the
      introduction of information and communication technology (ICT) to a well
      established ritual of medical autonomy (the medical ward round) to articulate a
      more nuanced explanation of how and why new ways of working with technology are
      accepted and adopted (or not). METHODS: The study was conducted across four
      intensive care units (ICUs) in major teaching hospitals in Sydney, Australia.
      Using interviews, we examined 48 doctors' perceptions of the impact of ICT on
      ward round practice. We applied the concept of institutional logics to frame our
      analysis. Interview transcripts were analysed using a hybrid of deductive and
      inductive thematic analysis. RESULTS: The doctors displayed a complex engagement
      with the technology that belies simplistic characterisations of medical rejection
      of managerial encroachment. In fact, they selectively welcomed into the ward
      round aspects of the technology which reinforced the doctor's place in the
      healthcare hierarchy and which augmented their role as scientists. At the same
      time, they guarded against allowing managerial logic embedded in ICT to de
      emphasise their embodied subjectivity in relation to the patient as a person
      rather than as a collection of parameters. CONCLUSION: ICT can force the
      disruption of some aspects of existing routines, even where these are long
      established rituals. Resistance arose when the new technology did not fit with
      the 'logic of care'. Incorporation of the logic of care into the design and
      customisation of clinical information systems is a challenge and potentially
      counterproductive, because it could attempt to apply a technological fix to what
      is essentially a social problem. However, there are significant opportunities to
      ensure that new technologies do not obstruct doctors' roles as carers nor disrupt
      the embodied relationship they need to have with patients.

PMID- 28750912
TI  - Development and initial evaluation of a mobile application to help with
      mindfulness training and practice.
AB  - BACKGROUND AND OBJECTIVE: Different review articles support the usefulness and
      effectiveness of mindfulness techniques in health and wellbeing. In this paper we
      present a first prototype of a mobile application to help with the training and
      practice of mindfulness, taking into account the lacks detected in a previous
      literature review. Our aim was to measure acceptance and perceived quality, as
      well as gather data about app usage. Their dependence on demographic variables
      and the change in mindful level was also measured. MATERIALS AND METHODS: Two
      versions of a new application were developed, "Mindfulness" and "Mindfulness
      Sci". The application has been tested in two pilot studies: in traditional face
      to-face mindfulness groups and in individual and independent use. RESULTS: 3977
      users were involved in this study: 26 in the first trial during an 8-week usage
      period and 3951 in the second trial during 17 months. In the first study,
      participants assessed the app with high scores. They considered it as a helping
      tool for mindfulness practice, user-friendly and with high quality of use. The
      positive perception was maintained after 8-weeks meditation workshops, and
      participants considered that its use could contribute to obtain benefits for
      mental and physical health. In the second study, we found rather weak
      associations between usage time and age, nationality and educational level. The
      mindful level showed a weak positive correlation with the session accomplished
      but slightly above the boundary of statistical significance (p-value=0.051).
      Videos and information stood out as the most accessed resources. CONCLUSIONS: Up
      to our knowledge, this is the first app developed with the help of health
      professionals in Spanish that could be used with a general aim, in health and
      wellbeing. The results are promising with a positive evaluation in face-to-face
      and independent use situations. Therefore, the number of potential users is
      enormous in a global worldwide context.

PMID- 28750913
TI  - Identification of key factors in consumers' adoption behavior of intelligent
      medical terminals based on a hybrid modified MADM model for product improvement.
AB  - BACKGROUND: As a new application technology of the Internet of Things (IoT),
      intelligent medical treatment has attracted the attention of both nations and
      industries through its promotion of medical informatisation, modernisation, and
      intelligentisation. Faced with a wide variety of intelligent medical terminals,
      consumers may be affected by various factors when making purchase decisions.
      PURPOSE: To examine and evaluate the key influential factors (and their
      interrelationships) of consumer adoption behavior for improving and promoting
      intelligent medical terminals toward achieving set aspiration level in each
      dimension and criterion. METHOD: A hybrid modified Multiple Attribute Decision
      Making (MADM) model was used for this study, based on three components: (1) the
      Decision-Making Trial and Evaluation Laboratory (DEMATEL) technique, to build an
      influential network relationship map (INRM) at both 'dimensions' and 'criteria'
      levels; (2) the DEMATEL-based analytic network process (DANP) method, to
      determine the interrelationships and influential weights among the criteria and
      identify the source-influential factors; and (3) the modified Vlse Kriterijumska
      Optimizacija I Kompromisno Resenje (VIKOR) method, to evaluate and improve for
      reducing the performance gaps to meet the consumers' needs for continuous
      improvement and sustainable products-development. First, a consensus on the
      influential factors affecting consumers' adoption of intelligent medical
      terminals was collected from experts' opinion in practical experience. Next, the
      interrelationships and influential weights of DANP among dimensions/criteria
      based on the DEMATEL technique were determined. Finally, two intelligent medicine
      bottles (AdhereTech, A1 alternative; and Audio/Visual Alerting Pillbox, A2
      alternative) were reviewed as the terminal devices to verify the accuracy of the
      MADM model and evaluate its performance on each criterion for improving the total
      certification gaps by systematics according to the modified VIKOR method based on
      an INRM. RESULTS: In this paper, the criteria and dimensions used to improve the
      evaluation framework are validated. The systematic evaluation in index system is
      constructed on the basis of five dimensions and corresponding ten criteria.
      Influential weights of all criteria ranges from 0.037 to 0.152, which shows the
      rank of criteria importance. The evaluative framework were validated
      synthetically and scientifically. INRM (influential network relation map) was
      obtained from experts' opinion through DEMATEL technique shows complex
      interrelationship among factors. At the dimension level, the environmental
      dimension influences other dimensions the most, whereas the security dimension is
      most influenced by others. So the improvement order of environmental dimension is
      prior to security dimension. The newly constructed approach was still further
      validated by the results of the empirical case, where performance gap improvement
      strategies were analyzed for decision-makers. The modified VIKOR method was
      especially validated for solving real-world problems in intelligent medical
      terminal improvement processes. For this paper, A1 performs better than A2,
      however, promotion mix, brand factor, and market environment are shortcomings
      faced by both A1 and A2. In addition, A2 should be improved in the wireless
      network technology, and the objective contact with a high degree of gaps.
      CONCLUSIONS: Based on the evaluation index system and the integrated model
      proposed here, decision-makers in enterprises can identify gaps when promoting
      intelligent medical terminals, from which they can get valuable advice to improve
      consumer adoption. Additionally, an INRM and the influential weights of DANP can
      be combined using the modified VIKOR method as integrated weightings to determine
      how to reduce gaps and provide the best improvement strategies for reaching set
      aspiration levels.

PMID- 28750914
TI  - Evolving techniques in text-based medical consultation - Physicians' long-term
      experiences at an Ask the doctor service.
AB  - INTRODUCTION: Both the demands and the options for patients to communicate with
      health care providers utilizing eHealth solutions are increasing. Some patients,
      or relatives to patients, want to consult another health care provider than the
      regular one, merely in text. OBJECTIVE: To improve text-based medical
      consultation by learning from long-term experiences. MATERIALS AND METHODS:
      Physicians with comprehensive experience of answering free-text medical inquiries
      at an official health portal in Sweden were interviewed. The interviews were
      analyzed using a grounded theory approach. RESULTS: Over time, the interviewed
      physicians developed strategies on how to formulate the answer to a medical
      inquiry from a previously unknown inquirer. The answering physicians experienced
      their primary role as providers of medical information and as mediators between
      an inquirer and the regular health care provider. Many of the answering
      physicians experienced a personal development with improved communication skills,
      also in face-to-face meetings with patients. CONCLUSION: Text-based medical
      consultation is part of an expanding area in eHealth. The development of
      strategies, guidelines, ethical considerations as well as educational efforts are
      needed to optimize the skills of asynchronous text-based health consultation.

PMID- 28750915
TI  - The informatics capability maturity of integrated primary care centres in
      Australia.
AB  - CONTEXT: Integrated primary care requires systems and service integration along
      with financial incentives to promote downward substitution to a single entry
      point to care. Integrated Primary Care Centres (IPCCs) aim to improve integration
      by co-location of health services. The Informatics Capability Maturity (ICM)
      describes how well health organisations collect, manage and share information;
      manage eHealth technology, implementation, change, data quality and governance;
      and use "intelligence" to improve care. AIM: Describe associations of ICM with
      systems and service integration in IPCCs. METHODS: Mixed methods evaluation of
      IPCCs in metropolitan and rural Australia: an enhanced general practice, four GP
      Super Clinics, a "HealthOne" (private-public partnership) and a Community Health
      Centre. Data collection methods included self-assessed ICM, document review,
      interviews, observations in practice and assessment of electronic health record
      data. Data was analysed and compared across IPCCs. FINDINGS: The IPCCs
      demonstrated a range of funding models, ownership, leadership, organisation and
      ICM. Digital tools were used with varying effectiveness to collect, use and share
      data. Connectivity was problematic, requiring "work-arounds" to communicate and
      share information. The lack of technical, data and software interoperability
      standards, clinical coding and secure messaging were barriers to data collection,
      integration and sharing. Strong leadership and governance was important for
      successful implementation of robust and secure eHealth systems. Patient
      engagement with eHealth tools was suboptimal. CONCLUSIONS: ICM is positively
      associated with integration of data, systems and care. Improved ICM requires a
      health workforce with eHealth competencies; technical, semantic and software
      standards; adequate privacy and security; and good governance and leadership.

PMID- 28750916
TI  - Understanding consumer health information-seeking behavior from the perspective
      of the risk perception attitude framework and social support in mobile social
      media websites.
AB  - OBJECTIVE: This study integrates the risk perception attitude framework and
      social support to examine factors influencing consumers' intentions to seek
      health information in mobile social media websites. METHOD: We develop a research
      model consisting of four social support dimensions, perceived health risk, health
      self-efficacy, and health information-seeking intention. A survey is conducted
      among patients with non-serious conditions. A two-step approach of structural
      equation modeling is used to test the research model. RESULTS: Among the four
      dimensions of social support, tangible support and appraisal support
      significantly influence perceived risk, whereas emotional support and esteem
      support significantly influence health self-efficacy. Perceived health risk and
      health self-efficacy significantly influence the health information-seeking
      behavior intention of consumers. Specifically, health self-efficacy significantly
      moderates the relationship between perceived risk and behavior intention.
      CONCLUSIONS: This study highlights the integrated effects of social capital and
      risk perception attitude framework on health information-seeking intention. It
      examines relationships among perceived health risk, health self-efficacy, and
      behavior intention in the mobile social media context. The findings help
      understand effects of social capital factors on perceived health risk and health
      self-efficacy.

PMID- 28750917
TI  - Predictive role of serum HBsAg and HBcrAg kinetics in patients with HBeAg
      negative chronic hepatitis B receiving pegylated interferon-based therapy.
AB  - OBJECTIVES: To investigate the role of serum hepatitis B core-related antigen
      (HBcrAg) kinetics in predicting long-term outcome of pegylated interferon (PEG
      IFN)-based therapy in patients with hepatitis B e antigen (HBeAg)-negative
      chronic hepatitis B (CHB). METHODS: A total of 121 Thai patients with HBeAg
      negative CHB recruited from a previous randomized trial of 48-week PEG-IFN alone
      or combined with entecavir were enrolled. Hepatitis B surface antigen (HBsAg) and
      HBcrAg levels were serially examined. Paired biopsy samples taken at baseline and
      after treatment were assessed for intrahepatic covalently closed circular DNA
      (cccDNA). RESULTS: Persistent virologic remission (PVR, defined by persistent
      hepatitis B virus (HBV) DNA <2000 IU/mL) and HBsAg clearance at 3 years after
      treatment were 29% (35/121) and 9% (11/121) respectively. Baseline HBcrAg
      correlated with HBV DNA and cccDNA but not with HBsAg. Baseline HBsAg, as well as
      HBsAg and HBcrAg, declines were associated with PVR, while HBsAg decline was
      predictive of HBsAg clearance. High baseline antigen levels (HBsAg >=3.4 log10
      IU/mL plus HBcrAg >=3.7 log10 U/mL) yielded high negative predictive values of
      PVR (45/50, 90%) and HBsAg clearance (50/50, 100%). At week 12, declines of
      HBsAg, HBcrAg and both antigens combined of <0.5 log10 yielded negative
      predictive values for PVR of 90% (71/79), 82% (61/74) and 96% (48/50)
      respectively. CONCLUSIONS: Quantitative HBcrAg was significantly associated with
      cccDNA in HBeAg-negative CHB. This novel antigen, together with HBsAg, could
      identify patients with low probability of PVR and HBsAg clearance in long-term
      follow-up.

PMID- 28750918
TI  - Susceptibilities of clinical Clostridium difficile isolates to antimicrobials: a
      systematic review and meta-analysis of studies since 1970.
AB  - OBJECTIVES: Although exposure to antibiotics can cause Clostridium difficile
      infection, certain antibiotics are used to treat C. difficile. Measurements of
      antimicrobial C. difficile activity could help to identify antibiotic risk and
      emergent resistance. Here, we describe publication patterns relating to C.
      difficile susceptibilities and estimate minimum inhibitory concentrations (MIC)
      for antibiotic classes in the published literature between January 1970 and June
      2014. METHODS: We queried PUBMED and EMBASE for studies reporting antibiotic C.
      difficile MIC in English or French. We used mixed-effects models to obtain pooled
      estimates of antibiotic class median MIC (MIC50), 90th percentile of MIC (MIC90),
      and MIC90:MIC50 ratio. RESULTS: Our search identified 182 articles that met our
      inclusion criteria, of which 27 were retained for meta-analysis. Aminoglycosides
      (MIC50 120 mg/L, 95% CI 62-250), 3rd (MIC50 75 mg/L, 95% CI 39-130) and 2nd
      generation cephalosporins (MIC50 64 mg/L, 95% CI 27-140) had the least C.
      difficile activity. Rifamycins (MIC50 0.034 mg/L, 95% CI 0.012-0.099) and
      tetracyclines (MIC50 0.29 mg/L, 95% CI 0.054-1.7) had the highest level of
      activity. The activity of 3rd generation cephalosporins was more than three times
      lower than that of 1st generation agents (MIC50 19 mg/L, 95% CI 7.0-54). Time
      trends in MIC50 were increasing for carbapenems (70% increase per 10 years) while
      decreasing for tetracyclines (51% decrease per 10 years). CONCLUSIONS: We found a
      3500-fold variation in antibiotic C. difficile MIC50, with aminoglycosides as the
      least active agents and rifamycins as the most active. Further research is needed
      to determine how in vitro measures can help assess patient C. difficile risk and
      guide antimicrobial stewardship.

PMID- 28750919
TI  - Central nervous system infections: work in progress.

PMID- 28750920
TI  - Antibiotic stewardship: does it work in hospital practice? A review of the
      evidence base.
AB  - BACKGROUND: Guidelines for developing and implementing stewardship programmes
      include recommendations on appropriate antibiotic use to guide the stewardship
      team's choice of potential stewardship objectives. They also include
      recommendations on behavioural change interventions to guide the team's choice of
      potential interventions to ensure that professionals actually use antibiotics
      appropriately in daily practice. AIMS: To summarize the evidence base of both
      appropriate antibiotic use recommendations (the 'what') and behavioural change
      interventions (the 'how') in hospital practice. SOURCES: Published systematic
      reviews/Medline. CONTENT: The literature shows low-quality evidence of the
      positive effects of appropriate antibiotic use in hospital patients. The
      literature shows that any behavioural change intervention might work to ensure
      that professionals actually perform appropriate antibiotic use recommendations in
      daily practice. Although effects were overall positive, there were large
      differences in improvement between studies that tested similar change
      interventions. IMPLICATIONS: The literature showed a clear need for studies that
      apply appropriate study designs- (randomized) controlled designs-to test the
      effectiveness of appropriate antibiotic use on achieving meaningful outcomes.
      Most current studies used designs prone to confounding by indication. In the
      process of selecting behavioural change interventions that might work best in a
      chosen setting, much should be learned from behavioural sciences. The challenge
      for stewardship teams lies in selecting change interventions on the careful
      assessment of barriers and facilitators, and on a theoretical base while linking
      determinants to change interventions. Future studies should apply more robust
      designs and evaluations when assessing behavioural change interventions.

PMID- 28750921
TI  - The methodology of surveillance for antimicrobial resistance and healthcare
      associated infections in Europe (SUSPIRE): a systematic review of publicly
      available information.
AB  - OBJECTIVES: Surveillance is a key component of any control strategy for
      healthcare-associated infections (HAIs) and antimicrobial resistance (AMR), and
      public availability of methodologic aspects is crucial for the interpretation of
      the data. We sought to systematically review publicly available information for
      HAIs and/or AMR surveillance systems organized by public institutions or
      scientific societies in European countries. METHODS: A systematic review of
      scientific and grey literature following the Preferred Reporting Items for
      Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed.
      Information on HAIs and/or AMR surveillance systems published until 31 October
      2016 were included. RESULTS: A total of 112 surveillance systems were detected;
      56 from 20 countries were finally included. Most exclusions were due to lack of
      publicly available information. Regarding AMR, the most frequent indicator was
      the proportion of resistant isolates (27 of 34 providing information, 79.42%);
      only 18 (52.9%) included incidence rates; the data were only laboratory based in
      33 (78.5%) of the 42 providing this information. Regarding HAIs in intensive care
      units, all 22 of the systems providing data included central line-associated
      bloodstream infections, and 19 (86.3%) included ventilator-associated pneumonia
      and catheter-associated urinary tract infections; incidence density was the most
      frequent indicator. Regarding surgical site infections, the most frequent
      procedures included were hip prosthesis, colon surgery and caesarean section
      (21/22, 95.5%). CONCLUSIONS: Publicly available information about the methods and
      indicators of the surveillance system is frequently lacking. Despite the efforts
      of European Centre for Disease Control and Prevention (ECDC) and other
      organizations, wide heterogeneity in procedures and indicators still exists.

PMID- 28750922
TI  - Elevation of CA19-9 and CEA is associated with a poor prognosis in patients with
      resectable gallbladder carcinoma.
AB  - AIMS: The aim of this study was to determine whether a combination of the tumour
      markers carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA19-9) would be
      helpful in predicting the prognosis of patients with gallbladder carcinoma (GBC)
      who underwent resection. METHODS: A retrospective analysis of clinico
      pathological features and survival of 390 patients with GBC who were treated
      between January 2003 and December 2013. Time-dependent receiver operating
      characteristic (ROC) was used to evaluate the prognostic ability of tumour
      markers. Combinations of preoperative CEA and CA19-9 were tested as potential
      prognostic factors. RESULTS: The evaluation of preoperative CEA and CA19-9 showed
      that patients with both tumour markers within the normal range had the best
      prognosis with a median survival of 27 months and R0 rate of 86%. Patients with
      both tumour markers elevated had the poorest prognosis and lower R0 rate (p <
      0.001). The combination of CEA and CA19-9 was an independent risk factor for
      overall survival. The AUROC at 5 years of combination of CEA and CA19-9 was
      0.798, which was similar to CEA (0.765) or CA19-9 (0.771) alone (p = 0.103, p =
      0.147). CONCLUSIONS: A combination of an elevated preoperative CEA and CA19-9 was
      associated with a worse prognosis for patients with GBC who underwent resection.

PMID- 28750923
TI  - Didox (3,4-dihydroxybenzohydroxamic acid) suppresses IL-33-induced cytokine
      production in primary mouse mast cells.
AB  - While IgE is considered the primary mediator of mast cell activation, IL-33
      contributes substantially in asthma, allergic rhinitis, and atopic dermatitis. To
      develop effective treatments for allergic disease, it is important to understand
      the role of therapeutic agents on IL-33 activation. We examined the effect of
      Didox (3,4-dihydroxybenzohydroxamic acid), an antioxidant and ribonucleotide
      reductase (RNR) inhibitor, on IL-33-mediated mast cell activation. Didox
      suppressed IL-6, IL-13, TNF, and MIP-1alpha (CCL3) production in bone marrow
      derived mast cells following IL-33 activation. This suppression was observed in
      different genetic backgrounds and extended to peritoneal mast cells. The
      antioxidant N-acetylcysteine mimicked the suppression of Didox, albeit at a much
      higher dose, while the RNR inhibitor hydroxyurea had no effect. Didox
      substantially suppressed IL-33-mediated NFkappaB and AP-1 transcriptional
      activities. These results suggest that Didox attenuates IL-33-induced mast cell
      activation and should be further studied as a potential therapeutic agent for
      inflammatory diseases involving IL-33.

PMID- 28750924
TI  - Global geographical variations in ST-segment elevation myocardial infarction
      management and post-discharge mortality.
AB  - BACKGROUND: There is a shortage of information on regional variations in ST
      segment elevation myocardial infarction (STEMI) management and prognosis at a
      global level. We aimed to compare patient profiles, in-hospital management and
      post-discharge mortality across several world regions. METHODS: In total, 11,559
      patients with STEMI were enrolled in two prospective studies of acute coronary
      syndrome survivors: EPICOR (4943 patients from 555 hospitals in 20 countries in
      Europe and Latin America recruited between September 2010 and March 2011) and
      EPICOR Asia (6616 patients from 218 hospitals in eight Asian countries recruited
      between June 2011 and May 2012). Comparisons were performed by eight pre-defined
      regions: Northern Europe (NE), Southern Europe (SE), Eastern Europe (EE), Latin
      America (LA), China (CN), India (IN), Southeast Asia (SA), and South Korea/Hong
      Kong/Singapore (KS). RESULTS: Reperfusion therapy rates ranged between 53.9% (IN)
      and 81.2% (SE), primary percutaneous coronary intervention (PCI) between 24.8%
      (IN) and 65.6% (NE) and fibrinolysis between 8.1% (CN) and 34.2% (SA). Median
      time to primary PCI (h) ranged from 3.9 (NE) to 20.9 (IN) and to fibrinolysis
      from 2.4 (SE) to 6.3 (IN). Two-year mortality ranged between 2.5% in NE and 7.4%
      in LA. Regional variations in mortality persisted after adjustment for
      reperfusion therapy and known prognostic factors. CONCLUSIONS: Among patients
      with STEMI, there is a wide regional variation in clinical profiles, hospital
      care and mortality. Substantial room for improvement remains at a global level
      for increasing reperfusion rates, reducing delays and post-discharge mortality in
      patients with STEMI.

PMID- 28750925
TI  - beta1,4-galactosyltransferase 1 is a novel receptor for IgA in human mesangial
      cells.
AB  - IgA nephropathy is characterized by mesangial deposition of IgA, mesangial cell
      proliferation, and extracellular matrix production. Mesangial cells bind IgA, but
      the identity of all potential receptors involved remains incomplete. The
      transferrin receptor (CD71) acts as a mesangial cell IgA receptor and its
      expression is upregulated in many forms of glomerulonephritis, including IgA
      nephropathy. CD71 is not expressed in healthy glomeruli and blocking CD71 does
      not completely abrogate mesangial cell IgA binding. Previously we showed that
      mesangial cells express a receptor that binds the Fc portion of IgA and now
      report that this receptor is an isoform of beta-1,4-galactosyltransferase. A
      human mesangial cell cDNA library was screened for IgA binding proteins and beta
      1,4-galactosyltransferase identified. Cell surface expression of the long isoform
      of beta-1,4-galactosyltransferase was shown by flow cytometry and confocal
      microscopy and confirmed by immunoblotting. Glomerular beta-1,4
      galactosyltransferase expression was increased in IgA nephropathy. IgA binding
      and IgA-induced mesangial cell phosphorylation of spleen tyrosine kinase and IL-6
      synthesis were inhibited by a panel of beta-1,4-galactosyltransferase-specific
      antibodies, suggesting IgA binds to the catalytic domain of beta-1,4
      galactosyltransferase. Thus, beta-1,4-galactosyltransferase is a constitutively
      expressed mesangial cell IgA receptor with an important role in both mesangial
      IgA clearance and the initial response to IgA deposition.

PMID- 28750927
TI  - Fibroblast growth factor 1 ameliorates diabetic nephropathy by an anti
      inflammatory mechanism.
AB  - Inflammation plays a central role in the etiology of diabetic nephropathy, a
      global health issue. We observed a significant reduction in the renal expression
      of fibroblast growth factor 1, a known mitogen and insulin sensitizer, in
      patients with diabetic nephropathy and in mouse models implying that fibroblast
      growth factor 1 possesses beneficial anti-inflammatory and renoprotective
      activities in vivo. To test this possibility, we investigated the effects of
      chronic intraperitoneal administration of fibroblast growth factor 1 into both
      the streptozotocin-induced type 1 diabetes and db/db type 2 diabetes models.
      Indeed, recombinant fibroblast growth factor 1 significantly suppressed renal
      inflammation (i.e., cytokines, macrophage infiltration), glomerular and tubular
      damage, and renal dysfunction in both type 1 and type 2 diabetes mice. Fibroblast
      growth factor 1 was able to correct the elevated blood glucose levels in type 2
      but not in type 1 diabetic mice, suggesting that the anti-inflammatory effect of
      fibroblast growth factor 1 was independent of its glucose-lowering activity. The
      mechanistic study demonstrated that fibroblast growth factor 1-mediated
      inhibition of the renal inflammation in vivo was accompanied by attenuation of
      the nuclear factor kappaB and c-Jun N-terminal kinase signaling pathways, further
      validated in vitro using cultured glomerular mesangial cells and podocytes. Thus,
      fibroblast growth factor 1 holds great promise for developing new treatments for
      diabetic nephropathy through countering inflammatory signaling cascades in
      injured renal tissue.

PMID- 28750926
TI  - Label-free molecular imaging of the kidney.
AB  - In this review, we will highlight technologies that enable scientists to study
      the molecular characteristics of tissues and/or cells without the need for
      antibodies or other labeling techniques. Specifically, we will focus on matrix
      assisted laser desorption/ionization imaging mass spectrometry, infrared
      spectroscopy, and Raman spectroscopy.

PMID- 28750928
TI  - Paricalcitol and cinacalcet have disparate actions on parathyroid oxyphil cell
      content in patients with chronic kidney disease.
AB  - The parathyroid oxyphil cell content increases in patients with chronic kidney
      disease (CKD), and even more in patients treated with the calcimimetic cinacalcet
      and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more
      calcium-sensing receptors than chief cells, suggesting that the calcium-sensing
      receptor and calcimimetics are involved in the transdifferentiation of a chief
      cell to an oxyphil cell type. Here, we compared the effect of the vitamin D
      analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on
      the oxyphil cell content in patients with CKD to further investigate the genesis
      of these cells. Parathyroid tissue from four normal individuals and 27 patients
      with CKD who underwent parathyroidectomy for secondary hyperparathyroidism were
      analyzed. Prior to parathyroidectomy, patients had received the following
      treatment: seven with no treatment, seven with cinacalcet only, eight with
      paricalcitol only, or cinacalcet plus paricalcitol in five. Oxyphilic areas of
      parathyroid tissue, reported as the mean percent of total tissue area per
      patient, were normal, 1.03; no treatment, 5.3; cinacalcet, 26.7 (significant vs.
      no treatment); paricalcitol, 6.9 (significant vs. cinacalcet; not significant vs.
      no treatment); and cinacalcet plus paricalcitol, 12.7. Cinacalcet treatment leads
      to a significant increase in parathyroid oxyphil cell content but paricalcitol
      does not, reinforcing a role for the calcium-sensing receptor activation in the
      transdifferentiation of chief-to-oxyphil cell type. Thus, two conventional
      treatments for hyperparathyroidism have disparate effects on parathyroid
      composition, and perhaps function. This finding is provocative and may be useful
      when evaluating future drugs for hyperparathyroidism.

PMID- 28750929
TI  - Blood pressure parameters are associated with all-cause and cause-specific
      mortality in chronic kidney disease.
AB  - Previous observational studies reported J or U-shaped associations between blood
      pressure parameters and mortality in patients with chronic kidney disease (CKD).
      Here we examined the associations of different blood pressure levels with various
      causes of death in a CKD population that included patients with eGFR 15-59
      ml/min/1.73 m2 with underlying hypertension receiving at least one
      antihypertensive agent. We obtained data on date and cause of death from State
      Department of Health mortality files and classified deaths into three categories:
      cardiovascular, malignancy-related, and non-cardiovascular/non-malignancy
      related. Cox models were fitted for overall mortality, and separate competing
      risk regression models for each major cause of death category, to evaluate their
      associations with various systolic and diastolic blood pressures. During a median
      follow-up of 3.9 years, 13,332 of 45,412 patients died. Systolic blood pressures
      under 100, 100-109, 110-119, and over 150 (vs. 130-139 mm Hg) were associated
      with higher all-cause and cardiovascular mortality. Systolic blood pressures
      under 100 mm Hg and 100-109 were associated with higher non-cardiovascular/non
      malignancy related mortality. Diastolic blood pressures under 50 and 50-59 (vs.
      70-79 mm Hg) were associated with higher all-cause and non-cardiovascular/non
      malignancy-related mortality while diastolic blood pressures over 90 mm Hg was
      associated with higher cardiovascular but lower non-cardiovascular/non-malignancy
      related mortality. Thus, in a non-dialysis dependent CKD population, systolic
      blood pressures under 110 and over 150 mm Hg were associated with cardiovascular
      and non-cardiovascular/non-malignancy related deaths. However, diastolic blood
      pressure under 60 mm Hg was associated in contrast with all-cause mortality and
      non-cardiovascular/non-malignancy-related deaths.

PMID- 28750930
TI  - Positive antineutrophil cytoplasmic antibody serology in patients with lupus
      nephritis is associated with distinct histopathologic features on renal biopsy.
AB  - Class IV-S lupus nephritis is often associated with more necrosis and fewer
      subendothelial immune deposits compared to class IV-G lupus nephritis, suggestive
      of necrotising glomerular inflammation found in antineutrophil cytoplasmic
      antibody (ANCA)-associated vasculitis. ANCAs are present in a significant
      proportion of patients with lupus nephritis. Here we determine whether ANCAs are
      associated with distinct clinical and histopathologic features of lupus
      nephritis. Thirty-two ANCA-positive biopsies were compared to 222 ANCA-negative
      biopsies from patients with lupus nephritis. The majority (82%) of ANCA-positive
      patients had antimyeloperoxidase antibodies. Class IV-S lupus nephritis and
      glomerular necrosis were significantly more common (36% vs. 16% and 35% vs. 15%,
      respectively) and isolated Class V lupus nephritis significantly less common (10%
      vs. 29%) in the ANCA-positive group. ANCA-positive patients had significantly
      higher dsDNA titers (335u/ml vs. 52u/ml), significantly lower serum C4
      concentrations (0.125g/L vs. 0.15g/L) and significantly higher serum creatinine
      (130MUmol/L vs. 84MUmol/L) at the time of biopsy. Hence ANCAs appear to influence
      the histological pattern of lupus nephritis and are associated with worse
      baseline renal function and more active lupus serology. There was no significant
      difference in outcome between groups when matched for severity of disease and
      treatment using propensity scoring. Thus, further studies are needed to examine
      whether ANCAs in patients with lupus nephritis have a pathogenic role and whether
      they are associated with worse renal outcomes or are simply a marker of more
      severe disease.

PMID- 28750932
TI  - Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Management and outcome of patients with operable chronic
      thromboembolic pulmonary hypertension (CTEPH) who underwent pulmonary
      endarterectomy (PEA) at a large German referral center were investigated.
      METHODS: In Germany, 394 PEAs were performed in 2014 and 2015 with an in-hospital
      mortality rate of 5.8%. Of these, 253 patients (64.2%) were treated at the
      Kerckhoff Clinic, Bad Nauheim, and 237 (93.7%; median age, 62 years
      [interquartile range [IQR], 52-72 years]; 46.0% female) were included in the
      present analysis. RESULTS: On referral, 52 patients (22.0%) were treated with
      pulmonary arterial hypertension-specific drugs and 95 (40.4%) were treated with
      non-vitamin K-dependent oral anticoagulants, and 14 (5.9%) had mean pulmonary
      artery pressure <25 mm Hg and were classified as having chronic thromboembolic
      pulmonary vascular disease. PEA was feasible in 236 (99.6%) patients with median
      duration of surgery of 397 minutes (IQR, 363-431 minutes). Periprocedural (0%)
      and in-hospital (2.5%) mortality rates were very low. Forty-two patients (17.7%)
      had intraoperative complications, and 60 (25.3%) had post-operative
      complications. The duration of surgery was the only predictor of in-hospital
      mortality (>=500 minutes; odds ratio [OR], 32.0; 95% confidence interval [CI],
      5.5-187.6) and the only independent predictor of intraoperative (>=440 minutes;
      OR, 10.8; 95% CI, 4.4-26.5) and post-operative (>=390 minutes; OR, 2.4; 95%CI,
      1.1-5.7) complications. Only intraoperative complications independently predicted
      a longer duration of surgery (>=397 minutes; OR, 5.0; 95% CI, 2.2-11.2).
      CONCLUSIONS: In an experienced center with multidisciplinary diagnostic and
      therapeutic approaches, PEA is safe. Prognosis was mainly determined by
      occurrence of intraoperative complications and duration of surgery rather than
      patients' pre-operative status.

PMID- 28750931
TI  - Factor H autoantibody is associated with atypical hemolytic uremic syndrome in
      children in the United Kingdom and Ireland.
AB  - Factor H autoantibodies can impair complement regulation, resulting in atypical
      hemolytic uremic syndrome, predominantly in childhood. There are no trials
      investigating treatment, and clinical practice is only informed by retrospective
      cohort analysis. Here we examined 175 children presenting with atypical hemolytic
      uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies
      that included 17 children with titers above the international standard. Of the
      17, seven had a concomitant rare genetic variant in a gene encoding a complement
      pathway component or regulator. Two children received supportive treatment; both
      developed established renal failure. Plasma exchange was associated with a poor
      rate of renal recovery in seven of 11 treated. Six patients treated with
      eculizumab recovered renal function. Contrary to global practice,
      immunosuppressive therapy to prevent relapse in plasma exchange-treated patients
      was not adopted due to concerns over treatment-associated complications. Without
      immunosuppression, the relapse rate was high (five of seven). However,
      reintroduction of treatment resulted in recovery of renal function. All patients
      treated with eculizumab achieved sustained remission. Five patients received
      renal transplants without specific factor H autoantibody-targeted treatment with
      recurrence in one who also had a functionally significant CFI mutation. Thus, our
      current practice is to initiate eculizumab therapy for treatment of factor H
      autoantibody-mediated atypical hemolytic uremic syndrome rather than plasma
      exchange with or without immunosuppression. Based on this retrospective analysis
      we see no suggestion of inferior treatment, albeit the strength of our
      conclusions is limited by the small sample size.

PMID- 28750933
TI  - Association between antibody functions and human cytomegalovirus (HCMV)
      replication after lung transplantation in HCMV-seropositive patients.

PMID- 28750934
TI  - SERCA2a: A potential non-invasive biomarker of cardiac allograft rejection.
AB  - BACKGROUND: The detection of heart transplant rejection by non-invasive methods
      remains a major challenge. Despite the well-known importance of the study of
      sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) in the heart, its role as a
      rejection marker has never been analyzed. Our objective in this study was to
      determine whether circulating SERCA2a could be a good marker of cardiac
      rejection. METHODS: We collected 127 consecutive endomyocardial biopsies (EMBs)
      and serum samples from adult heart transplant recipients (49 without allograft
      rejection and 78 with the diagnosis of biopsy allograft rejection, including 48
      Grade 1R, 21 Grade 2R and 9 Grade 3R). Serum concentrations of SERCA2a were
      determined using a specific sandwich enzyme-linked immunosorbent assay. We also
      analyzed SERCA2a expression changes on EMBs using immunofluorescence. RESULTS:
      SERCA2a cardiac tissue and serum levels were decreased in patients with cardiac
      rejection (p < 0.0001). A receiver-operating characteristic analysis showed that
      SERCA2a strongly discriminated between patients with and without allograft
      rejection: normal grafts vs all rejecting grafts (AUC = 0.804); normal grafts vs
      Grade 1R (AUC = 0.751); normal grafts vs Grade 2R (AUC = 0.875); normal grafts vs
      Grade 3R (AUC = 0.922); normal grafts vs Grade 2R and 3R (AUC = 0.889), with p <
      0.0001 for all comparisons. CONCLUSIONS: We demonstrated that changes in SERCA2a
      cardiac tissue and serum levels occur in cardiac allograft rejection. Our
      findings suggest that SERCA2a concentration assessment may be a relatively
      simple, non-invasive test for heart transplant rejection, showing a strong
      capability for detection that improves progressively as rejection grades
      increase.

PMID- 28750935
TI  - Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1
      infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non
      inferiority trial.
AB  - BACKGROUND: Cabotegravir and rilpivirine are antiretroviral drugs in development
      as long-acting injectable formulations. The LATTE-2 study evaluated long-acting
      cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through
      96 weeks. METHODS: In this randomised, phase 2b, open-label study, treatment
      naive adults infected with HIV-1 initially received oral cabotegravir 30 mg plus
      abacavir-lamivudine 600-300 mg once daily. The objective of this study was to
      select an intramuscular dosing regimen based on a comparison of the antiviral
      activity, tolerability, and safety of the two intramuscular dosing regimens
      relative to oral cabotegravir plus abacavir-lamivudine. After a 20-week induction
      period on oral cabotegravir plus abacavir-lamivudine, patients with viral
      suppression (plasma HIV-1 RNA <50 copies per mL) were randomly assigned (2:2:1)
      to intramuscular long-acting cabotegravir plus rilpivirine at 4-week intervals
      (long-acting cabotegravir 400 mg plus rilpivirine 600 mg; two 2 mL injections) or
      8-week intervals (long-acting cabotegravir 600 mg plus rilpivirine 900 mg; two 3
      mL injections) or continued oral cabotegravir plus abacavir-lamivudine.
      Randomisation was computer-generated with stratification by HIV-1 RNA (<50 copies
      per mL, yes or no) during the first 12 weeks of the induction period. The primary
      endpoints were the proportion of patients with viral suppression at week 32 (as
      defined by the US Food and Drug Administration snapshot algorithm), protocol
      defined virological failures, and safety events through 96 weeks. All randomly
      assigned patients who received at least one dose of study drug during the
      maintenance period were included in the primary efficacy and safety analyses. The
      primary analysis used a Bayesian approach to evaluate the hypothesis that the
      proportion with viral suppression for each long-acting regimen is not worse than
      the oral regimen proportion by more than 10% (denoted comparable) according to a
      prespecified decision rule (ie, posterior probability for comparability >90%).
      Difference in proportions and associated 95% CIs were supportive to the primary
      analysis. The trial is registered at ClinicalTrials.gov, number NCT02120352.
      FINDINGS: Among 309 enrolled patients, 286 were randomly assigned to the
      maintenance period (115 to each of the 4-week and 8-week groups and 56 to the
      oral treatment group). This study is currently ongoing. At 32 weeks following
      randomisation, both long-acting regimens met primary criteria for comparability
      in viral suppression relative to the oral comparator group. Viral suppression was
      maintained at 32 weeks in 51 (91%) of 56 patients in the oral treatment group,
      108 (94%) of 115 patients in the 4-week group (difference 2.8% [95% CI -5.8 to
      11.5] vs oral treatment), and 109 (95%) of 115 patients in the 8-week group
      (difference 3.7% [-4.8 to 12.2] vs oral treatment). At week 96, viral suppression
      was maintained in 47 (84%) of 56 patients receiving oral treatment, 100 (87%) of
      115 patients in the 4-week group, and 108 (94%) of 115 patients in the 8-week
      group. Three patients (1%) experienced protocol-defined virological failure (two
      in the 8-week group; one in the oral treatment group). Injection-site reactions
      were mild (3648 [84%] of 4360 injections) or moderate (673 [15%] of 4360
      injections) in intensity and rarely resulted in discontinuation (two [<1%] of 230
      patients); injection-site pain was reported most frequently. Serious adverse
      events during maintenance were reported in 22 (10%) of 230 patients in the
      intramuscular groups (4-week and 8-week groups) and seven (13%) of 56 patients in
      the oral treatment group; none were drug related. INTERPRETATION: The two-drug
      combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4
      weeks or every 8 weeks was as effective as daily three-drug oral therapy at
      maintaining HIV-1 viral suppression through 96 weeks and was well accepted and
      tolerated. FUNDING: ViiV Healthcare and Janssen R&D.

PMID- 28750936
TI  - Long-acting injectable ART: next revolution in HIV?

PMID- 28750937
TI  - Castor oil for induction of labor in post-date pregnancies: A randomized
      controlled trial.
AB  - BACKGROUND: Castor oil is a substance used for labor induction in an inpatient
      setting. However, its efficacy as an agent for the induction of labor, for post
      date pregnancies in an outpatient setup is unknown. OBJECTIVE: Efficacy of castor
      oil as an agent for the induction of labor, for post-date pregnancies in
      outpatient settings. METHODS: Eighty-one women with a low-risk post-date
      singleton pregnancy with a Bishop score<=7, without effective uterine
      contractions were randomized to the intervention, 60ml of castor oil, or the
      control, 60ml of sun-flower oil. The primary outcome was proportion of women
      entering the active phase of labor 24, 36, 48h after ingestion. Secondary
      outcomes included meconium stained amniotic fluid, abnormal fetal heart rate
      tracing, cesarean section rate, instrumental deliveries, birth weight, 5min Apgar
      score, chorioamnionitis, hypertensive complications, retained placenta, and post
      partum hemorrhage. FINDINGS: Intervention and control groups included 38 and 43
      women, respectively. No differences in baseline characteristics, except for age
      were noted. The observed interaction between castor oil and parity was
      significant (pinteraction=0.02). Multiparous women in the intervention group
      exhibited a significant beneficial effect on entering active labor within 24, 36
      and 48h after castor oil consumption compared with the placebo (Hazard
      Ratio=2.93, p=0.048; Hazard Ratio=3.29, p=0.026; Hazard Ratio=2.78, p=0.042
      respectively). This effect was not noted among primiparous women. No differences
      in rate of obstetric complications or adverse neonatal outcomes were noted.
      CONCLUSION: Castor oil is effective for labor induction, in post-date multiparous
      women in outpatient settings.

PMID- 28750938
TI  - Impact of cryopreservation method on dromedary camel ovary structure, viability,
      and development of antral follicular oocytes.
AB  - The objectives of this study were, a) to compare two different vitrification
      techniques, the solid surface vitrification (SSV) and direct vitrification (DV)
      method, b) to evaluate the effect of four cryoprotectant agents and their
      toxicity on the morphological appearance and ultrastructural of camel ovarian
      cortex, c) to examine the development of oocytes recovered from the vitrified
      ovarian cortex. Fragments of ovarian cortex were exposed to equilibration
      solution consisting of TCM- 199 with 10% fetal camel serum (FCS); 0.10M sucrose
      and including one of the following cryoprotectants; 20% glycerol (GLY); 3.5M
      ethylene glycol (EG); 3.5M propanediol (PROH) or 3M dimethylsulphoxide (DMSO).
      After vitrification of ovarian fragments, they were warmed and evaluated by
      histological and transmission electron microscope. The oocytes isolated from
      vitrified ovarian cortex were cultured in TCM-199 at 38.5 degrees C under 5% CO2
      for 44h. Maturation was indicated through cumulus expansion and calculated by
      oocytes reaching first telophase and second metaphase (TI+MII). The percentage of
      morphologically normal and viable follicles of SSV was significantly higher
      P<0.05 than DV group (52.9 vs. 38.1, respectively). In conclusion, viability,
      histological and ultrastructural observations revealed that SSV method and
      ethylene glycol-based freezing solution were able to remain morphology better
      follicle and oocyte. Additionally, most organelles of oocytes are able to recover
      their normal morphology in camel ovarian cortex following cryopreservation and
      thawing processes, and oocytes isolated from vitrified ovarian cortex can exhibit
      maturation and reaches to (TI+MII).

PMID- 28750939
TI  - Corrigendum to "Oral health 4 life: Design and methods of a semi-pragmatic
      randomized trial to promote oral health care and smoking abstinence among tobacco
      quitline callers" [Contemp. Clin. Trials 57 (2017) 90-97].

PMID- 28750940
TI  - Lifestyle Risk Factors Increase the Risk of Hospitalization for Sciatica:
      Findings of Four Prospective Cohort Studies.
AB  - BACKGROUND: The purpose of this study is to assess the effects of lifestyle risk
      factors on the risk of hospitalization for sciatica and to determine whether
      overweight or obesity modifies the effect of leisure-time physical activity on
      hospitalization for sciatica. METHODS: We included 4 Finnish prospective cohort
      studies (Health 2000 Survey, Mobile Clinic Survey, Helsinki Health Study, and
      Young Finns Study) consisting of 34,589 participants and 1259 hospitalizations
      for sciatica during 12 to 30 years of follow-up. Sciatica was based on hospital
      discharge register data. We conducted a random-effects individual participant
      data meta-analysis. RESULTS: After adjustment for confounding factors, current
      smoking at baseline increased the risk of subsequent hospitalization for sciatica
      by 33% (95% confidence interval [CI], 13%-56%), whereas past smokers were no
      longer at increased risk. Obesity defined by body mass index increased the risk
      of hospitalization for sciatica by 36% (95% CI 7%-74%), and abdominal obesity
      defined by waist circumference increased the risk by 41% (95% CI 3%-93%). Walking
      or cycling to work reduced the risk of hospitalization for sciatica by 33% (95%
      CI 4%-53%), and the effect was independent of body weight and other leisure
      activities, while other types of leisure activities did not have a statistically
      significant effect. CONCLUSIONS: Smoking and obesity increase the risk of
      hospitalization for sciatica, whereas walking or cycling to work protects against
      hospitalization for sciatica. Walking and cycling can be recommended for the
      prevention of sciatica in the general population.

PMID- 28750941
TI  - Acute and sub-chronic toxicity studies of the aqueous extract from leaves of
      Cistus ladaniferus L. in mice and rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cistus ladaniferus L. (C.ladaniferus) (Cistaceae)
      is an aromatic shrub native to the Mediterranean region. The leaves are widely
      used in traditional medicine throughout Morocco for the treatment of various
      diseases including, diabetes, diarrhea, inflammation, and skin ailments. However,
      to the best of our knowledge, no systematic study concerning its toxicity profile
      has been reported. AIM OF THE STUDY: The study carried out evaluates the
      potential toxicity of the aqueous extract from leaves of the C.ladaniferus (CL
      extract) shrub, through the method of acute and sub-chronic oral administration
      in mice and rats. MATERIALS AND METHODS: During the acute toxicity study, male
      and female mice were orally administrated with CL aqueous extract at single doses
      of 500, 1000, 2000, 3000 and 5000mg/kg (n = 5/group/sex). Abnormal behavior,
      toxic symptoms, weight, and death were observed for 14 consecutive days to assess
      the acute toxicity. During the sub-chronic toxicity study, the aqueous extract
      was administered orally at doses of 500, 700 and 1000mg/kg (n = 6/group) daily to
      Wistar rats of both sexes for 90 days. The general behavior of the rats was
      observed daily, and their body weight was recorded weekly. A urinalysis,
      biochemical analysis, hematological analysis, macroscopic examination and
      histopathological examination of several organs were conducted at the end of the
      treatment period. RESULTS: During the acute toxicity test, when mice were
      administered doses of 3000 and 5000mg/kg, the CL extract produced a 10-30%
      mortality rate, respectively, and induced signs of toxicity. However, no
      mortality or adverse effect was noted at the doses of 1000 and 2000mg/kg. The
      median lethal dose (LD50) of the extract was estimated to be more than 5000mg/kg.
      In the subchronic study, the CL extract induced no mortality or treatment-related
      adverse effects with regard to body weight, general behavior, relative organ
      weights, urine, hematological, and biochemical parameters. Histopathological
      examination of vital organs showed normal architecture suggesting no
      morphological alterations. Moreover, the CL extracts improved lipid profile and
      exhibited a significant hypoglycemic effect in all doses tested in rats.
      CONCLUSION: The results of the present study suggest that treatment with the CL
      extract for 13 weeks does not appear to produce significant toxicity, except at
      high dose. Therefore, the use of appropriate levels of the CL extract as a
      traditional medicine remedies should have a wide margin of safety for its
      therapeutic use.

PMID- 28750942
TI  - A standardized extract of the fruit of Hovenia dulcis alleviated alcohol-induced
      hangover in healthy subjects with heterozygous ALDH2: A randomized, controlled,
      crossover trial.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hovenia dulcis, known as the oriental raisin
      tree, is mainly found in East Asia. It has long been used as traditional folk
      remedies for alcohol intoxication. AIM OF THE STUDY: To examine the anti-hangover
      effect of Hovenia dulcis Thunb. fruit extract (HDE) in a randomized controlled
      crossover trial. MATERIALS AND METHODS: Twenty-six eligible male adults with
      heterozygous ALDH2 (23.7+/-0.3 years old) consumed 360mL of Korean Soju (50g
      alcohol) together with HDE (2460mg) or matched placebo with subsequent crossover.
      The blood samples were taken at baseline and 1, 4, and 12h post-treatment.
      RESULTS: Blood alcohol, acetaldehyde, and total hangover scores were highest at
      1h post-treatment with no difference between groups, but declines in hangover
      symptom scores were significant in the HDE group compared to the placebo group.
      Significant differences between groups were also observed on interleukin (IL)-6,
      IL-10, IL-10/IL-6 ratio, and aspartate aminotransferase levels, but not on
      endotoxins. Pearson correlation analysis revealed a positive correlation between
      total hangover symptom scores and IL-6 and IL-10 level. Further analyses by
      CYP2E1 polymorphism at rs10776687, rs2031920, rs3813867, and rs4838767 alleles
      showed a reversed association, suggesting that CYP2E1 polymorphism might be an
      effect modifier. CONCLUSIONS: The results suggest that a favorable effect of HDE
      on alcohol hangovers might be associated with enhancing homeostatic regulation of
      inflammatory response. The magnitude of impact might be different in the presence
      of CYP2E1 polymorphism.

PMID- 28750943
TI  - Effect of Preterm Birth on Echogenicity in Basal Ganglia.
AB  - In this study, the influence of prematurity on echogenicity of deep gray matter
      at 30-wk corrected age was assessed using ultrasound measurements. In an
      observational cohort study, ultrasound scans of 224 extremely preterm infants
      were prospectively collected. Gray values were assessed in putamen and globus
      pallidus. Intra- and inter-observer reliability was analyzed and showed excellent
      agreement. The globus pallidus to putamen ratio was significantly related to
      gestational age at birth, adjusted regression coefficient in points per wk: 1.28
      (95% confidence interval [CI]: 0.38-2.19) for left and 2.12 (95% CI: 1.23-3.02)
      for right-side images. At 30-wk corrected age this was still the case, adjusted
      regression coefficient: 0.45 (95% CI: -0.57 to 1.47) for left and 1.29 (95% CI:
      0.10-2.48) for right. The putamen is more hyperechoic with lower gestational age.
      Measuring ultrasound gray values in deep gray matter seems highly reproducible.
      Prematurity shows a negative correlation with echogenicity of the putamen, this
      persists at 30-wk corrected age, suggesting altered maturation.

PMID- 28750944
TI  - Vector and Doppler Ultrasound Velocities Evaluated in a Flow Phantom and the
      Femoropopliteal Vein.
AB  - Ultrasound is used for evaluating the veins of the lower extremities. Operator
      and angle dependency limit spectral Doppler ultrasound (SDUS). The aim of the
      study was to compare peak velocity measurements in a flow phantom and the
      femoropopliteal vein of 20 volunteers with the angle-independent vector velocity
      technique vector flow imaging (VFI) and SDUS. In the flow phantom, VFI
      underestimated velocity (p = 0.01), with a lower accuracy of 5.5% (p = 0.01) and
      with no difference in precision, that is, error factor, compared with SDUS (VFI:
      1.02 vs. SDUS: 1.02, p = 0.58). In vivo, VFI estimated lower velocities (femoral:
      p = 0.001; popliteal: p = 0.001) with no difference in precision compared with
      SDUS (femoral: VFI 1.09 vs. SDUS 1.14, p = 0.37; popliteal: VFI 1.13 vs. SDUS
      1.06, p = 0.09). In conclusion, the precise VFI technique can be used to
      characterize venous hemodynamics of the lower extremities despite its
      underestimation of velocities.

PMID- 28750945
TI  - High prevalence of rare ryanodine receptor type 1 variants in patients suffering
      from aneurysmatic subarachnoid hemorrhage: A pilot study.
AB  - Subarachnoid hemorrhage (SAH) remains a challenging neurosurgical disease. The
      ryanodine receptor type 1 Ca2+ channel (RyR1) plays a crucial role in
      vasoconstriction and hemostasis. Mutations of the encoding gene, RYR1, are known
      to cause susceptibility to malignant hyperthermia (MH). Recently, a RYR1 mutation
      was found to be associated with abnormal bleeding times. Therefore, an assessment
      of the RYR1 gene might be of high relevance in patients with aneurysmatic SAH. In
      the presented pilot study, we screened 10 patients suffering from SAH for RYR1
      variants and, for the first time in SAH, performed an assessment of pathogenicity
      of these variants using protein prediction software. Four of the patients showed
      a RYR1 variant. For three of the variants, p.Glu79Lys, p.Arg885C, p.Glu2635 Val,
      all three programs predicted pathogenicity. Their prevalence in the general
      population is very low i.e. under 0.005%. For the fourth variant, p.Pro4501Leu
      (RS73933023), the results of the prediction programs were discrepant and the
      prevalence in the general population was high, i.e. almost 0.5%, which is too
      frequent to be associated with the rare SAH phenotype. Clinical evaluation
      revealed that no differences concerning neurological outcome, presence of
      vasospasm, ischemic deficits and mean hospital stay between patients with and
      without variants were found. However, in our series SAH patients have an
      increased frequency of rare RYR1 variants. Hence, potentially contributing to the
      pathogenesis of SAH. Further data is needed to confirm this preliminary result.

PMID- 28750946
TI  - Changes in the axial orientation of the zygapophyseal joint in the subaxial
      cervical spine from childhood to middle-age, and the biomechanical implications
      of these changes.
AB  - The objective of this study was to investigate the effect of age on facet
      orientation (FO) of the cervical spine during development, maturation, and
      degeneration. Computed tomography (CT) data of the cervical spine of 131 subjects
      without pathology of the cervical spine were analyzed. Subjects were categorized
      as: pediatric (n=36, 8-16years old), young adult (n=33, 18-24years old), and
      middle-age (n=62, 40-59years old). Serial CT scans were reconstructed by image
      processing. The FO in the axial plane was measured bilaterally at each vertebral
      level from C3/4 to C6/7. Differences in FO were analyzed between the 3 groups.
      The degree of external rotation of FO significantly decreased at C3/4 and C4/5
      with increasing in age, and maximum external rotation was observed at C5/6. The
      external rotation at C6/7 increased from pediatric to young adulthood, but
      decreased from young adults to middle-aged adults. The dominant external rotation
      was seen in C4/5 and C5/6 in the pediatric age group, C5/6 and C6/7 in young
      adults, and C4/5 and C5/6 in middle-aged adults. These results lead us to
      conclude that FO in the axial plane exhibits significant differences with age.
      The degree of external rotation with respect to FO at each vertebral level is
      comparable to changes in cervical spinal dynamics with age. Hence, FO in the
      axial plane is a biomechanical parameter that can be used to assess changes in
      the cervical spinal during maturation and degeneration.

PMID- 28750947
TI  - Polymyxins for CNS infections: Pharmacology and neurotoxicity.
AB  - Central nervous system (CNS) infections caused by multi-drug resistant (MDR) Gram
      negative bacteria present a major health and economic burden worldwide. Due to
      the nearly empty antibiotic discovery pipeline, polymyxins (i.e. polymyxin B and
      colistin) are used as the last-line therapy against Gram-negative 'superbugs'
      when all other treatment modalities have failed. The treatment of CNS infections
      due to multi-drug resistant Gram-negative bacteria is problematic and associated
      with high mortality rates. Colistin shows significant efficacy for the treatment
      of CNS infections caused by MDR Gram-negative bacteria that are resistant to all
      other antibiotics. In particular, MDR Acinetobacter baumannii, Pseudomonas
      aeruginosa and Klebsiella pneumoniae which are resistant to expanded-spectrum and
      fourth-generation cephalosporins, carbapenems and aminoglycosides, represent a
      major therapeutic challenge, although they can be treated with colistin or
      polymyxin B. However, current dosing recommendations of
      intrathecal/intraventricular polymyxins are largely empirical, as we have little
      understanding of the pharmacokinetics/pharmacodynamics and, importantly, we are
      only starting to understand the mechanisms of potential neurotoxicity. This
      review covers the current knowledge-base on the mechanisms of disposition and
      potential neurotoxicity of polymyxins as well as the combined use of
      neuroprotective agents to alleviate polymyxins-related neurotoxicity. Progress in
      this field will provide the urgently needed pharmacological information for safer
      and more efficacious intrathecal/intraventricular polymyxin therapy against life
      threatening CNS infections caused by Gram-negative 'superbugs'.

PMID- 28750949
TI  - A machine learning approach for real-time modelling of tissue deformation in
      image-guided neurosurgery.
AB  - OBJECTIVES: Accurate reconstruction and visualisation of soft tissue deformation
      in real time is crucial in image-guided surgery, particularly in augmented
      reality (AR) applications. Current deformation models are characterised by a
      trade-off between accuracy and computational speed. We propose an approach to
      derive a patient-specific deformation model for brain pathologies by combining
      the results of pre-computed finite element method (FEM) simulations with machine
      learning algorithms. The models can be computed instantaneously and offer an
      accuracy comparable to FEM models. METHOD: A brain tumour is used as the subject
      of the deformation model. Load-driven FEM simulations are performed on a
      tetrahedral brain mesh afflicted by a tumour. Forces of varying magnitudes,
      positions, and inclination angles are applied onto the brain's surface. Two
      machine learning algorithms-artificial neural networks (ANNs) and support vector
      regression (SVR)-are employed to derive a model that can predict the resulting
      deformation for each node in the tumour's mesh. RESULTS: The tumour deformation
      can be predicted in real time given relevant information about the geometry of
      the anatomy and the load, all of which can be measured instantly during a
      surgical operation. The models can predict the position of the nodes with errors
      below 0.3mm, beyond the general threshold of surgical accuracy and suitable for
      high fidelity AR systems. The SVR models perform better than the ANN's, with
      positional errors for SVR models reaching under 0.2mm. CONCLUSIONS: The results
      represent an improvement over existing deformation models for real time
      applications, providing smaller errors and high patient-specificity. The proposed
      approach addresses the current needs of image-guided surgical systems and has the
      potential to be employed to model the deformation of any type of soft tissue.

PMID- 28750948
TI  - Mitochondrial function requires NGLY1.
AB  - Mitochondrial respiratory chain (RC) diseases and congenital disorders of
      glycosylation (CDG) share extensive clinical overlap but are considered to have
      distinct cellular pathophysiology. Here, we demonstrate that an essential
      physiologic connection exists between cellular N-linked deglycosylation capacity
      and mitochondrial function. Following identification of altered muscle and liver
      mitochondrial amount and function in two children with a CDG subtype caused by
      NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human
      fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
      Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a
      consistent disruption of mitochondrial physiology was present involving modestly
      reduced mitochondrial content with more pronounced impairment of mitochondrial
      membrane potential, increased mitochondrial matrix oxidant burden, and reduced
      cellular respiratory capacity. Lentiviral rescue restored NGLY1 expression and
      mitochondrial physiology in human and mouse fibroblasts, confirming that NGLY1
      directly influences mitochondrial function. Overall, cellular deglycosylation
      capacity is shown to be a significant factor in mitochondrial RC disease
      pathogenesis across divergent evolutionary species.

PMID- 28750950
TI  - New Tools for Cryptosporidium Lead to New Hope for Cryptosporidiosis.
AB  - The pyrazolopyridine KDU731 is a promising drug candidate for treatment of
      diarrhea caused by Cryptosporidium in young children in the resource-limited
      world. KDU731, a PI (4) kinase inhibitor, blocks Cryptosporidium infection in
      vitro and in vivo in immunocompromised mice and dramatically reduces oocyst
      shedding, diarrhea, and dehydration in neonatal calves.

PMID- 28750952
TI  - Letter to Editor: Application of neuroplasticity theory through the use of the
      Feldenkrais Method with a runner with scoliosis and lower quarter pain:
      Additional respiratory mechanics principle, implication of the Feldenkrais method
      for clinical practice in neuro-musculoskeletal rehabilitation.

PMID- 28750953
TI  - A concise rehabilitation protocol for sub-acute and chronic non-specific neck
      pain.
AB  - There is increasing evidence in support of multidisciplinary approaches for
      management of chronic neck pain. Although presence of different team members is
      one of the strengths of these approaches, it can limit the access to these
      treatments. The main objective of this study is designing and investigating the
      efficacy of a concise rehabilitation program. Thirty-nine patients with sub-acute
      and chronic non-specific neck pain underwent an 8-week rehabilitation program.
      Baseline and 8 weeks' follow-up data regarding neck pain (visual analog scale,
      neck disability index and quality of life) were compared using paired T test.
      After eight weeks of study, pain and disability significantly decreased: -3.8 of
      10 (95% CI: -4.6 to -3.0) (p-value < 0.001) for pain and -18.4 of 100 (95% CI: 
      23.7 to -13.2) (p-value < 0.001) for disability. Also, all SF-36 domain scales
      improved significantly. By using this concise rehabilitation approach, pain,
      disability, and quality of life improved significantly in patients with sub-acute
      and chronic non-specific neck pain.

PMID- 28750954
TI  - Exercise and physical therapy help restore body and self in clients with severe
      anorexia nervosa.
AB  - Exercise in the context of anorexia nervosa is a multifaceted endeavour
      surrounded by controversy and uncertainty. A broader comprehension of this poorly
      understood phenomenon is required. Informed by the findings of a body examination
      of six individuals with anorexia nervosa, as well as exercise science,
      phenomenology and neurocognition, the purpose of this article is to elaborate on
      the potential role of exercise and physical therapy in the treatment of anorexia
      nervosa. The findings of the body assessment include constriction of posture,
      muscles and pattern of breathing. These bodily restraints are not necessarily
      merely associated with high levels of exercise, they may also reflect
      psychological strain accompanying the illness. The restricted breathing in
      particular is assumed to be associated with difficult thoughts and suppressed
      feelings. Based on the results of the body examination, as well as medical and
      psychological considerations accompanying the illness, it is suggested that
      interventions should focus on improving postural stability and restoring related
      muscular function. Integral to engaging in these activities, the potential to
      integrate proprioceptive information in this process may generate a more coherent
      experience of the body, as well as of the self, in these clients. Accordingly,
      constrictions of the body may have a vital role in constraining the experience of
      the self. As such, addressing bodily restraints in these clients may facilitate
      the experience of being the subject causing and controlling the movements. This
      is in marked contrast to clients' previous exercise experiences, which were
      associated with compulsion, rigidity and the absence of coherence and control.

PMID- 28750955
TI  - Acute electromyographic responses of deep thoracic paraspinal muscles to spinal
      manual therapy interventions. An experimental, randomized cross-over study.
AB  - This single group, randomized, cross-over study explored whether manual therapy
      alters motor tone of deep thoracic back muscles by examining resting
      electromyographic activity (EMG) after 2 types of manual therapy and a sham
      control intervention. Twenty-two participants with thoracic spinal pain (15
      females, 7 males, mean age 28.1 +/- 6.4 years) had dual fine-wire, intramuscular
      electrodes inserted into deep transversospinalis muscles at a thoracic level
      where tissues appeared abnormal to palpation (AbP) and at 2 sites above and below
      normal and non-tender to palpation (NT). A surface electrode was on the
      contralateral paraspinal mass at the level of AbP. EMG signals were recorded for
      resting prone, two 3-s free neck extension efforts, two 3-s resisted maximal
      voluntary isometric contractions (MVIC), and resting prone before the
      intervention. Randomized spinal manipulation, counterstrain, or sham manipulation
      was delivered and EMG re-measured. Participants returned 1 and 2 weeks later for
      the remaining 2 treatments. Reductions in resting EMG followed counterstrain in
      AbP (median decrease 3.3%, P = 0.01) and NT sites (median decrease 1.0%, P =
      0.05) and for the surface electrode site (median decrease 2.0%, P = 0.009).
      Reduction in EMG following counterstrain during free neck extension was found for
      the surface electrode site (median decrease 2.7%, P < 0.01). Spinal manipulation
      produced no change in EMG, whereas counterstrain technique produced small
      significant reductions in paraspinal muscle activity during prone resting and
      free neck extension conditions. The clinical relevance of these changes is
      unclear.

PMID- 28750956
TI  - Therapeutically efficient components of Basic Body Awareness Therapy as perceived
      by experienced therapists - A qualitative study.
AB  - BACKGROUND: Basic Body Awareness Therapy (BBAT) is a physiotherapeutic method
      used in rehabilitation to increase physical and emotional balance. The aim was to
      identify and describe perceived therapeutically efficient components of BBAT.
      METHODS: Twenty-four experienced BBAT therapists participated in focus group
      interviews. The data were analysed with content analysis. RESULTS: One central
      theme, the therapeutic space consisted of two categories; the therapeutic
      encounter and the therapeutic tools, which emerged as the core of the perceived
      therapeutically efficient components. The therapeutic encounter entailed the
      therapeutic approach, affect attunement, continuous interaction during treatment,
      affect mirroring and communicating by use of a person-centred approach. The
      therapeutic tools included adjustment and adaptation, the use of manual, verbal
      and non-verbal guiding, and creating an atmosphere of safety and sanctuary.
      CONCLUSION: The significance of interaction by use of a person-centred approach
      combined with the ability to continuously adjust the treatment constituted useful
      guidelines when designing rehabilitation using BBAT treatment.

PMID- 28750957
TI  - Effects of aerobic exercise on functional capacity, anthropometric measurements
      and inflammatory markers in diabetic elderly women.
AB  - This study investigated the effects of an aerobic training program on functional
      capacity [Timed Up and Go test (TUG), timed 10-m walk test (10MWT), five
      repetition sit-to-stand test (5-STS), handgrip strength test (HGS) and one-legged
      stance test (OLS)], anthropometric measurements [body mass, body mass index
      (BMI), waist and hip circumferences and waist-to-hip ratio] and plasma levels of
      inflammatory markers [soluble tumor necrosis factor receptors 1 and 2, and
      interleukins 6 and 10] in 43 elderly women with type 2 diabetes mellitus. After
      the training, a significant improvement was observed in the performance of the
      participants on the TUG, 10MWT, 5-STS and HGS and in the anthropometric measures
      of body mass, BMI and hip circumference. None of the inflammatory markers showed
      a significant difference between pre- and post-training. The aerobic exercise
      program improved the functional capacity of diabetic elderly women, but was
      ineffective to change the levels of the inflammatory markers evaluated.

PMID- 28750958
TI  - Muscle strength and stiffness in resistance exercise: Force transmission in
      tissues.
AB  - Physical therapists and osteopaths want to know the quantitative force
      transmitted in the tissues during resistance exercise and also the relationship
      between tissue strength and the specific type of resistance exercise of the
      skeletal muscles. This paper uses the strain energy function for large
      deformations associated with the active and passive response of transversely
      isotropic skeletal muscle tissue to evaluate muscle strength and force
      transmitted in tissues during resistance exercises for the quadriceps muscle at
      the knee during isometric training exercise at different knee angles in vivo. It
      is found that after an exercise program, the muscle stiffness is halved when the
      bending angle of the knee increases from 50 degrees  to 100 degrees . The muscle
      strength generated is marginally greater at 100 degrees  than at 50 degrees . The
      stress transmitted in the lateral direction for 100 degrees  bending is double
      that for 50 degrees .

PMID- 28750959
TI  - Bodily symptoms in patients with post traumatic stress disorder: A comparative
      study of traumatized refugees, Danish war veterans, and healthy controls.
AB  - BACKGROUND: Post traumatic stress disorder (PTSD) is associated with increased
      general health symptoms and patients suffer from numerous bodily complaints such
      as increased pain, increased muscular tension, and restricted breathing. METHODS
      AND MATERIAL: This study applied the Body Awareness Movement Quality and
      Experience scale (BAS MQ-E) in assessing and comparing bodily symptoms, including
      movement function, in traumatized refugees (N = 14) and Danish war veterans with
      PTSD (N = 19) and healthy controls (N = 20). RESULTS: Patients with PTSD had
      significantly poorer stability, balance, flexibility and coordination in
      movement, had more muscular tension, more complaints of pain, more restricted
      breathing, and more limitation in function of daily life than healthy controls.
      CONCLUSION: The BAS MQ-E was found to be an applicable and useful measure of
      bodily symptoms in patients with PTSD. Further research may add to the validity
      of BAS MQ-E and might be considered in future studies evaluating the efficacy of
      physiotherapy for patients with PTSD.

PMID- 28750960
TI  - The effects of opposite-directional static contraction of the muscles of the
      right upper extremity on the ipsilateral right soleus H-reflex.
AB  - The objective of this study was to explore the neurophysiological remote after
      effects of resistive static contraction (SC) of the muscles of the upper
      extremity, considering the resistant direction on the ipsilateral (right) soleus
      H-reflex. The participants included 12 normal subjects with a mean (SD) age of
      23.8 (2.8) years. The subjects were asked to maintain their upper extremity
      against the traction force, at a level of resistance that was 50% of the maximal
      SC strength. A 20-s SC of the muscles of the upper extremity utilizing
      contraction of the upper extremity muscles using a diagonal flexion (shoulder
      flexion-adduction-external rotation) or extension (shoulder extension-abduction
      internal rotation), a proprioceptive neuromuscular facilitation (PNF) pattern was
      induced. The traction force line of the diagonal flexion or extension direction
      ran parallel to the diagonal line from the left acromion process to the right
      ASIS. Three-way analysis of variance of the H/Mmax ratio with Scheffe's post-hoc
      tests revealed that the H/Mmacorrelatex ratio of SC via diagonal extension was
      significantly smaller than that via diagonal flexion and that the H/Mmax ratio
      during the 120-140 s phase after SC, as remote after-effect SC, was significantly
      smaller than that during SC. The induction of neurophysiological descending
      effects for inhibition requires consideration of the force direction.

PMID- 28750961
TI  - Pathoanatomical characteristics of temporomandibular dysfunction: Where do we
      stand? (Narrative review part 1).
AB  - Temporomandibular dysfunction (TMD) is a complicated and multifactorial condition
      that affects the temporomandibular joint (TMJ) and muscles of mastication,
      resulting in pain and disability in 5-12% of the population. The condition
      involves genetic, anatomic and hormonal factors and is propagated, in part, by
      trauma, habitual activity, psychosocial components and occlusal variation. Yet,
      the exact etiology of TMD is still unknown and the most strategic conservative
      management of the condition is still a topic of debate. The purpose of this
      paper, the first of a two part series, is to provide greater insight into the
      pathoanatomical factors associated with TMD. Consistent with Scully (2008, 2013),
      degenerative changes seem to disrupt the relationship between the TMJ capsule,
      articular disc and muscles of mastication. The resulting position of the
      articular disc coincides with three primary classifications of TMD: Type 1
      (muscle disorders), Type 2a/b (disc displacement with and without reduction), and
      Type 3 (any joint pain). Given the association of the lateral pterygoid with both
      the joint capsule and articular disc, the superior and inferior head seem to play
      a key role in TMD. Both heads undergo biological changes associated with the
      vicious cycle, pain adaptation and integrated pain adaptation, making the muscle
      a key pain generator associated with TMD. Clinicians must understand the
      pathoanatomic features associated with TMD so as to choose appropriate treatment
      strategies, leading to optimal short and long-term outcomes. While the former is
      discussed in part 1 of this narrative review, the latter will be considered in
      part 2.

PMID- 28750962
TI  - Conservative management of temporomandibular dysfunction: A literature review
      with implications for clinical practice guidelines (Narrative review part 2).
AB  - The effective management of temporomandibular dysfunction (TMD) requires a
      thorough understanding of the pathoanatomic factors that drive the underlying
      condition. After reviewing the etiology associated with TMD in Part 1 of this
      narrative review, the temporomandibular joint capsule, articular disc and muscles
      of mastication emerged as key players.
      (http://dx.doi.org/10.1016/j.jbmt.2017.05.017) Part 2 focuses on conservative
      treatment strategies best able to reduce the pain and disability associated with
      TMD. A review of the literature revealed limited support of strengthening
      exercises targeting the muscles of mastication. There was also limited evidence
      for manual soft tissue work targeting muscles of mastication, which may be
      specifically related to the limited accessibility of the pterygoid muscles to
      palpation. For the reduction of pain, there was little to no evidence supporting
      splint therapy and electrophysical modalities, including laser therapy,
      ultrasound, TENs and iontophoresis. However, for the reduction of pain and
      disability, non-thrust mobilization and high-velocity, low amplitude thrust
      manipulation techniques to the TMJ and/or upper cervical articulations that
      directly and indirectly target the TMJ joint capsule were generally supported in
      the literature. Studies that used dry needling or acupuncture of the lateral
      pterygoid and posterior, peri-articular connective tissue also led to significant
      improvements in pain and disability in patients with TMD. Thus, the most
      effective conservative management of TMD seems to be techniques best able to
      impact anatomic structures directly related to the etiology of TMD, to include
      the joint capsule, articular disc and muscles of mastication, specifically the
      superior and inferior head of the lateral pterygoid.

PMID- 28750963
TI  - Relationship between hardness and deformation of the vastus lateralis muscle
      during knee flexion using ultrasound imaging.
AB  - The aims of this study were to clarify the relationship between deformation of
      the VL during knee flexion and the stiffness of the VL. 40 lower limbs of 20 male
      normal volunteers were divided into control and tightness groups using the Ely
      test. Deformation of the VL in the transverse plane during active knee flexion
      from 0 to 90 degrees  was recorded using B-mode ultrasonography. Hardness of the
      VL was measured on the middle lateral thigh using a durometer. The reaction force
      at fully passive flexion was measured using a hand held dynamometer. The
      deformation of the VL and the hardness and passive torque showed significant
      differences between the 2 groups. The deformation of the VL showed a
      significantly higher correlation with hardness of the VL. Measurements of the
      deformation of the VL might be predicted by the elasticity around the VL.

PMID- 28750964
TI  - Comparison of ischemic compression and lumbopelvic manipulation as trigger point
      therapy for patellofemoral pain syndrome in young adults: A double-blind
      randomized clinical trial.
AB  - OBJECTIVE: To compare the effectiveness of ischemic compression (IC) directly to
      the vastus medialis obliquus (VMO) versus lumbopelvic manipulation (LPM) in
      improving pain, functional status and sensitivity to mechanical stimulation of
      the VMO trigger point in patients with patellofemoral pain syndrome (PFPS).
      PARTICIPANTS: 40 patients with unilateral PFPS aged 20-30 years were selected
      randomly among patients with unilateral PFPS referred to physical therapy clinics
      of Shiraz University of Medical Sciences in Shiraz, Iran, between March 2014 and
      July 2014. 30 young adults participated. Participants were blinded to treatment
      allocation, and 15 patients were allocated to either IC or LPM. INTERVENTIONS:
      Patients in both groups were treated in three sessions per week. IC consisted of
      three sets of continuous pressure applied for on the myofascial trigger point
      (MTrP) of VMO. LPM consisted of supine rotational glide manipulation of the
      ipsilateral lumbopelvic region of the involved knee. MAIN OUTCOME MEASURES:
      Numeric pain rating scale (VAS) for pain intensity, Kujala questionnaire for
      functional status, and pressure pain threshold (PPT) for sensitivity to
      mechanical stimulation. All three were recorded before treatment, 1 week, 1 month
      and 3 months after the last session. RESULTS: Both groups showed significant
      improvement (p < 0.05, 95% confidence interval) in pain, functional status and
      PPT values. However, the IC group showed greater improvements, and outcome
      measures remained significantly better than in the LPM group during post
      intervention follow-up. CONCLUSIONS: Both groups showed improvements throughout
      the study and follow-up period. However, the IC showed better short-term and long
      term effectiveness than LPM for treating PFPS.

PMID- 28750965
TI  - Effect of therapeutic Swedish massage on anxiety level and vital signs of
      Intensive Care Unit patients.
AB  - OBJECTIVE: To evaluate how Swedish massage affects the level of anxiety and vital
      signs of Intensive Care Unit (ICU) patients. METHODS: Quasi-experimental study.
      INCLUSION CRITERIA: ICU patients, 18-50 years old, cooperative, respiratory and
      hemodynamic stable, not under invasive mechanical ventilation. EXCLUSION
      CRITERIA: allergic to massage oil, vascular or orthopedic post-operative, skin
      lesions, thrombosis, fractures. A 30-min Swedish massage was applied once.
      VARIABLES: arterial pressure, heart rate, respiratory rate, S-STAI questionnaire.
      Timing of evaluation: pre-massage, immediately post-massage, 30 min post-massage.
      Comparison: T-test, corrected by Bonferroni method, level of significance of 5%,
      confidence interval of 95%. RESULTS: 48 patients included, 30 (62.5%) female,
      mean age 55.46 (15.70) years old. Mean S-STAI pre-massage: 42.51 (9.48);
      immediately post-massage: 29.34 (6.37); 30 min post-massage: 32.62 (8.56), p <
      0.001 for all comparison. Mean vital signs achieved statistical significance
      between pre-massage and immediately post-massage. CONCLUSION: Swedish massage
      reduced anxiety of ICU patients immediately and 30 min post-massage. Vital signs
      were reduced immediately post-massage.

PMID- 28750966
TI  - The effectiveness of osteopathic manipulative treatment in an abnormal uterine
      bleeding related pain and health related quality of life (HR-QoL) - A case
      report.
AB  - Abnormal uterine bleeding is characterized by painful and/or excessive menorrhea,
      chronic pelvic pain due to the endometriosis (Em). Osteopathic treatment is
      commonly used in the gynecological dysfunctions. The aim of the present case
      study was to explore the effect of osteopathic treatment (OT) for a woman with
      abnormal uterine bleeding related pain and quality of life (QoL). We reported a
      case of 29 year old female who presented with chief complaints of increased flow
      during periods, lower abdominal pain, leukorrhoea, lower back pain and with
      occasional constipation for the last 3 years. Patient is a mother of 6 years old
      male child born with normal delivery. On diagnostic ultrasonography the uterus
      was found bulky with insignificant endometriosis and no other abnormality was
      detected. She did not have any relevant past medical and surgical history. The
      pre and post osteopathic treatment measurements were measured using Visual Analog
      Scale (VAS) and the health related quality of life (HR-QoL) questionnaire called
      short form Endometriosis Health Profile Questionnaire (EHP) - 5. In the present
      case the pain due to the endometriosis was treated with the osteopathic treatment
      consists of all the major diaphragms' release (release of pelvic diaphragm,
      abdominal diaphragm, thoracic outlet release and hyoid diaphragm) during the
      first session and in the second session gastro-esophageal (GE) junction release,
      sigmoid colon release, cranial therapy to the occiput, sacral release and dural
      tube rocking. Following that improvement of pain from VAS 8.3/10 to 3.9/10 and
      QoL improvement from EHP-5, 72/100 to 26/100 was noted. Osteopathic manipulative
      approach (OMA) in the patient with Em might improve the abnormal uterine bleeding
      related pain and health related quality of life (HR-QoL).

PMID- 28750967
TI  - Joint amplitude MEMS based measurement platform for low cost and high
      accessibility telerehabilitation: Elbow case study.
AB  - This paper, presents an inertial and magnetic sensor based technological
      platform, intended for articular amplitude monitoring and telerehabilitation
      processes considering an efficient cost/technical considerations compromise. The
      particularities of our platform offer possibilities of a high social impact by
      making telerehabilitation accessible to large population sectors in marginal
      socio-economic sectors, especially in underdeveloped countries where, in contrast
      to developed countries, specialists are scarce and high technology is not
      available or inexistent. This platform integrates high resolution low cost
      inertial and magnetic sensors with adequate user interfaces and communication
      protocols to perform a diagnostic service through the web, or other available
      communication networks. Elbow amplitude information is generated by sensors and
      then transferred to a computing device with adequate interfaces to make it
      accessible to inexperienced personnel, providing a high social value at a low
      cost. Experimental methodology includes two different sets of tests: the first
      one uses flexion - extension movements on a robotic arm to validate our platform
      (IMOCAP) articular amplitude measurements, against the robotic positioning
      system. The second set of tests was carried out on human patients to test IMOCAP
      in real operational conditions; results were validated with an optical
      positioning system. This paper presents experimental results showing the platform
      applicability to telerehabilitation processes.

PMID- 28750968
TI  - Different weight bearing push-up plus exercises with and without isometric
      horizontal abduction in subjects with scapular winging: A randomized trial.
AB  - The aim of the present study was to determine whether the application of
      isometric horizontal abduction (IHA) differentially affected two weight-bearing
      push-up plus exercises by examining activation of the scapulothoracic muscles in
      subjects with scapular winging. Fifteen male subjects performed standard push-up
      plus (SPP) and wall push-up plus (WPP), with and without IHA. Two-way analyses of
      variance using two within-subject factors were used to determine the statistical
      significance of observed differences in upper trapezius (UT), pectoralis major
      (PM), and serratus anterior (SA) muscle activities and UT/SA and PM/SA muscle
      activity ratios. UT and SA muscle activities were greater during SPP than WPP. PM
      muscle activity was lower with IHA application. The UT/SA and PM/SA muscle
      activity ratios were lower during SPP than WPP. The PM/SA muscle activity ratio
      was lower with IHA application. The results suggest that IHA application using a
      Thera-Band can effectively reduce PM muscle activity during SPP and WPP
      exercises. Moreover, the SPP exercise can be used to increase UT and SA muscle
      activity and reduce the UT/SA and PM/SA muscle activity ratios in subjects with
      scapular winging.

PMID- 28750969
TI  - A case study utilizing myofascial release, acupressure and trigger point therapy
      to treat bilateral "Stringhalt" in a 12 year old Akhal-Teke horse.
AB  - "Stringhalt" is a horse condition that causes one or both hind legs to spasm when
      walking, trotting or backing. The condition is thought to be related to a
      neurological cause from either plant toxicity or peripheral nerve injury. The
      prognosis is poor and the horse's performance and quality of life can be
      affected. Treatment has included surgically cutting the digital extensors with
      varied results. The objective of the study is to utilize soft tissue release via
      acupressure, trigger point and myofascial release to decrease symptoms of
      stringhalt. The case study is a 12 year old Akhal-Teke horse of excellent
      pedigree. In 2011, she was caught in barbed wire overnight and sustained
      lacerations to the bone in her hindlimbs. Shortly after the injury the horse was
      placed in a stall for several months and was unable to walk or run, developing
      stringhalt. Currently, her condition is aggravated by stress and alleviated by
      certain types of massage (myofascial, acupressure, and trigger point release).
      The incidence of stringhalt occurs every 3-5 min, with more frequent and severe
      symptoms on the right hindlimb. The horse is unable to run or back up. Six 1 to
      11/2 hour bi-weekly treatments were performed. The treatments consisted of
      myofascial release at the cervical, sacrum and iliums, acupressure of the bladder
      meridian (including c-spine, t-spine, l-spine, and hamstring), and trigger point
      release of the iliacus. The stringhalt symptoms were monitored for 30 min prior
      to each of the 6 treatment sessions. After 6 treatments, the horse was observed
      running and standing in a position that promotes hip extension. She has not been
      able to do either since the injury. The frequency and severity of the spasms have
      decreased to every 10-20 min. The horse's owners report that her disposition,
      stress and quality of life are much improved. The results suggest that myofascial
      release, acupressure and trigger point therapy may be utilized to provide a
      positive treatment outcome in the case of stringhalt. However, please note that
      the scope of practice varies by state and special training is needed to work with
      the equine population.

PMID- 28750970
TI  - The effect of Tai Chi exercises on postural stability and control in older
      patients with knee osteoarthritis.
AB  - A few studies have examined the effect of Tai Chi on balance in elder patients
      with knee osteoarthritis (OA). The aim of this study was to determine the balance
      measures in elder patients with knee OA after Tai Chi exercises. For this purpose
      14 females and 6 males with knee OA were chosen. Area and mean velocity of the
      center of pressure movements (CoP) were measured by force plate in standing
      positions (on foam and rigid surfaces). The measurements of area and mean
      velocity of CoP were performed before and after 60 min of Tai Chi sessions (twice
      a week for 8 weeks). The results showed that the area of CoP in standing position
      on rigid surface was significantly decreased (P < 0.01) after Tai Chi exercises.
      Furthermore, the mean velocity of CoP was significantly decreased after Tai Chi
      exercises on both rigid and foam surfaces (P < 0.001). Our study also indicated
      that changes in surfaces (rigid and foam) would cause significant differences
      regarding the area of CoP in standing positions. However, similar findings were
      not found regarding the mean velocity of CoP. Considering the effects of Tai Chi
      on mean velocity of CoP, it might be concluded that motor control and postural
      stability improvements have occurred. Therefore, based on these results, Tai Chi
      exercises could be recommended for elder patients with knee OA as part of their
      rehabilitation and physical therapy protocols.

PMID- 28750971
TI  - The influence of physical fitness on pressure pain threshold of elderly women.
AB  - Several factors may influence pressure pain threshold (PPT), including physical
      fitness. However, only a few authors have studied this relationship. The aim of
      this study was to investigate the relationships between muscle strength,
      functional capacity (ability to perform physical work and activities of daily
      living) and PPT in elderly women. This observational cross-sectional study
      involved 75 healthy women aged between 60 and 75 years. Volunteers underwent an
      evaluation consisting of anthropometry, functional capacity, muscle strength and
      PPT assessment by algometry in the following muscles: biceps brachii, flexor
      carpi ulnaris, flexor carpi radialis, vastus medialis, vastus lateralis and
      gluteus maximus. Mean age of the 75 volunteers was 66.8 +/- 4.6 years old. No
      significant correlations were found between handgrip or elbow flexion strength
      and PPT in the upper limb muscles evaluated. The same was observed regarding
      functional capacity, lower limbs strength and PPT in lower limb muscles.
      Functional capacity and muscle strength did not correlate with PPT in healthy
      elderly women.

PMID- 28750972
TI  - Lower limb muscular activity during walking at different speeds: Over-ground
      versus treadmill walking: A voluntary response evaluation.
AB  - OBJECTIVE: To evaluate the overall lower limb muscular activity pattern during
      treadmill walking compared to over-ground walking. METHODOLOGY: The study was
      conducted on 25 healthy young females. Surface electromyography was recorded from
      gastrocnemius, hamstrings, vasti and gluteus medius muscles during walking over
      ground and treadmill at 3 different speeds (comfortable, slow and fast). The
      pattern of muscle activity was compared between two walking conditions at
      different speeds by the voluntary response index method. Voluntary response index
      is composed of two numeric values: magnitude which represents the strength of
      overall muscular activity, and similarity index which represents the resemblance
      of overall muscle activity. RESULTS: The main effect of walking conditions and
      speed as well as their interaction effect (P < 0.001) on magnitude of muscle
      activity were significant but not for similarity index. CONCLUSIONS: The pattern
      of muscular activity during walking on treadmill and over-ground was similar but
      walking on treadmill induced higher muscular activity in the lower limb
      musculature.

PMID- 28750973
TI  - Manipulation of the body schema - Unilateral manual stimulation of lower
      extremity influences weight distribution in standing position.
AB  - Clinical experience advocates sensory stimulation to increase the body sensation
      and adjust the body schema, which may be disturbed in some patients. Unilateral
      massage may affect the body midline orientation, but little evidence is available
      to support the effect of this practice. Twenty-one healthy young people
      participated in this experimental study. Two force plates measured weight
      distribution between the legs in standing position before and after unilateral
      manual stimulation of the lower extremities. Stimulation of the leg with initial
      least weight-bearing increased the load on this leg significantly from 48.2% to
      49.0% and a similar but reverse effect was seen when stimulating the contra
      lateral leg. When analysing the data with respect to stimulation of the non
      dominant leg, the stimulation increased the weight-bearing on this leg from 49.6%
      to 51.3%. These findings indicate that external afferent stimuli may enhance the
      body perception and influence the body schema and midline orientation.

PMID- 28750974
TI  - Does kinesiology tape increase trunk forward flexion?
AB  - INTRODUCTION: Non specific lower back pain is a common musculoskeletal disorder
      in manual labourers due to the strenuous nature of their job. Fear of pain can
      cause restrictions in trunk movement leading to reduced flexibility. Kinesiology
      Tape (KT) may be an option for treating low back stiffness. The present study
      investigated the immediate effect of KT on trunk flexion active range of motion.
      METHOD: 34 male participants (mean age +/- SD: 42 +/- 11), in physically
      demanding jobs, asymptomatic of pain, with a history of non specific lower back
      pain were randomly assigned to: 1) KT Intervention (KTI) or 2) KT Placebo (KTP).
      Trunk flexion data was collected at baseline and immediately following tape
      application. ANCOVA was used to examine the differences between groups. RESULTS:
      The KTI group demonstrated a statistically significant gain in Trunk flexion
      compared with baseline (2.75 cm, P < 0.05). Changes from pre to post treatment
      for the KTP were not significant (1.57 cm, P = 0.062). No statistically
      significant differences existed between groups post-treatment (P = 0.218).
      CONCLUSION: KTI demonstrates an immediate positive effect on trunk flexion when
      compared with baseline measurements. However, results suggest that KTI performs
      no better than a comparable placebo.

PMID- 28750975
TI  - The effects of inter-trial interval on implicit learning of sequential visual
      isometric pinch task.
AB  - Sequential visual isometric pinch task (SVIPT) has been recently used as a
      visuomotor sequence task in clinical research. The influence of varying intervals
      between sequenced trials on the acquisition of implicit sequence learning is not
      yet determined for SVIPT. The aim of this study was to investigate the effects of
      inter-trial interval (ITI) on implicit motor sequence learning using SVIPT. A
      total of 32 healthy participants with mean age 31.3 +/- 4.5 years participated in
      this study. Participants were randomly assigned to one of four ITI groups; (1, 2,
      3 and 4 s). They were instructed to control their force on a force transducer to
      reach a number of targets which appeared on the computer screen by changing the
      pinch force exerted onto the transducer. In this study, outcome measures were
      movement time, error rate and skill, which were measured before and after
      training. Our results indicated that motor sequence learning similarly affected
      various ITIs. Indeed, all participants exhibited same improvement in implicit
      learning of SVIPT even though the ITIs varied from 1 to 4 s. Our findings suggest
      that implicit learning of SVIPT is independent of ITI within this range in
      healthy individuals.

PMID- 28750976
TI  - Scapular dyskinesis among competitive swimmers.
AB  - AIM: To evaluate the prevalence of scapular dyskinesis (SD) in competitive
      swimmers during training sessions. METHODS: Repeated measurement observational
      study.20 young competitive swimmers were filmed before, at midpoint and at the
      end of a training session, performing shoulder flexion and abduction. SD was
      examined separately by two assessors. Demographic and Quick Disabilities of the
      Arm, Shoulder, and Hand questionnaires were collected. RESULTS: SD was observed
      in 30% of the swimmers before training, in 70%, an hour later, and in 80%, upon
      completion of the training session. The difference between the baseline and mid
      practice was close to significance (p-value = 0.055), and between mid-practice
      and end of practice was significant (p = 0.004). CONCLUSIONS: This study
      confirmed that the prevalence of SD increases throughout a training session in
      most swimmers. The main reason might be fatigue of the muscles which stabilize
      the scapula, therefore, when examining a sportsmen's shoulder, it is important to
      examine the SD post-training or following simulation of the training session in
      the clinic.

PMID- 28750977
TI  - Isometric endurance test of the cervical flexor muscles - Reliability and
      normative reference values.
AB  - OBJECTIVE: To obtain reference values for the isometric endurance test (IET) of
      the cervical flexor muscles, investigate its reproducibility, and compare the
      results with the maximal isometric strength test (MIST) of the cervical flexor
      muscles. DESIGN: Cross-sectional non-comparative study with single group repeated
      measurements. METHODS: Altogether 219 healthy females aged 20-59 years
      volunteered to participate in the study. The IET was performed in the supine
      position and MIST seated. The reproducibility was evaluated by the intraclass
      correlation coefficient (ICC) and an analysis described by Bland and Altman. The
      relationship between the two measuring methods was evaluated by Pearson's
      correlation coefficient. RESULTS: The mean (SD) IET time was 60 (33) seconds with
      no significant differences between the age groups of each decade. The ICC for
      intrarater repeatability was 0.80. However, the Bland-Altman analysis suggested
      moderate variation in repeated measurements. Pearson's correlation coefficient
      between the IET and MIST was 0.56. CONCLUSION: Normative reference values for the
      IET are presented. Although the ICC showed good repeatability, one should
      consider that the change at follow-up visits has to be considerable to be
      clinically relevant. The correlation between the endurance time and maximal
      flexion strength was moderate. Thus IET of the cervical flexor muscles may be
      used in the clinic like the Biering-Sorenson test has been used to assess fatigue
      of the trunk extensor muscles.

PMID- 28750978
TI  - A myofascial component of pain in knee osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is the most common cause of musculoskeletal pain
      and disability. The knee is the most common site of OA. Numerous studies have
      shown an inconsistency between patients' reports of pain and their radiographic
      findings. This inconsistency may be partially explained by the fact that a
      portion of the pain originates from the myofascial trigger points (MTrPs) located
      in the surrounding muscles. AIM: To assess the role of myofascial pain in OA
      patients. METHODS: Critical review. PubMed, Google Scholar, Scopus, and PEDro
      databases were searched from inception until December 2016 for the following
      keywords: "myofascial pain", "osteoarthritis", "trigger points", "knee" or any
      combination of these words. The reference lists of all articles retrieved were
      searched as well. RESULTS: The current review included two observational studies
      evaluating the prevalence of MTrPs in OA patients and six interventional studies
      describing the treatment of myofascial pain in OA patients. Data from two of the
      interventional studies also included an observational section. CONCLUSION: The
      reviewed observational studies offered initial evidence as to the assumption that
      myofascial pain and the presence of MTrPs may play a role in pain and disability
      of knee OA. Because of the cross-sectional design of these studies, the causal
      relationships could not be established. Additional studies are needed to confirm
      this assumption as well as to clarify if MTrPs are a portion of OA etiology or
      that OA is the basis for MTrPs formation. Each interventional study elaborated on
      various myofascial treatment techniques. However, treatment focusing on MTrPs
      seems to be effective in reducing pain and improving function in OA patients. Due
      to the heterogeneity in treatment methods and outcome measures, it is difficult
      to attain a definite conclusion and therefore, additional high-quality randomized
      controlled trials are warranted.

PMID- 28750979
TI  - Acute effects of self-myofascial release and stretching in overhead athletes with
      GIRD.
AB  - OBJECTIVE: To examine the acute effects of self-myofascial release (SMR), static
      stretching (SS), and the combination of self-myofascial release and static
      stretching (SMR + SS) on glenohumeral internal rotation range of motion (GH IR
      ROM) in overhead athletes with glenohumeral internal rotation deficit (GIRD).
      PARTICIPANTS: Twelve asymptomatic adult male amateur softball position players
      exhibiting GIRD. RESULTS: All three methods significantly improved GH IR ROM.
      Post hoc testing revealed that SS alone and SMR + SS improved GH IR ROM
      significantly more than SMR alone. However, there were no significant differences
      in GH IR ROM between SS alone and SMR + SS. CONCLUSIONS: If an athlete has a
      limited time to perform a warm-up (e.g., 3-4 min), SS alone is recommended to
      improve GH IR ROM. However, if the athlete has more time available to warm up
      (e.g., 7-8 min), combining SMR + SS may result in a greater increase in GH IR
      ROM.

PMID- 28750980
TI  - Successful treatment of rotator cuff tear using Fascial Manipulation(r) in a
      stroke patient.
AB  - Rotator cuff tear is a common disease affecting patients after stroke. It's a
      cause of pain and dysfunction that may compromise normal stroke rehabilitation.
      For many cases there is still controversy between whether to use surgical or
      conservative intervention. Treatment for cuff tears range from physical therapy
      to surgery. This paper describes for the first time the effect of Fascial
      Manipulation(r) (FM(r)) on rotator cuff tear in a post stroke patient. A 69 year
      old female stroke patient with full absence of distal components of the tendons
      of the rotator cuff, functional limitations on active movement of shoulder
      flexion and abduction of the left arm and perceived pain scored 10/10 on the
      Visual Analogic Scale, was assessed and treat with one session of FM(r) A basic
      theory that explains the healing results of FM(r) is that mechanoreceptors, such
      as spindle cells and other receptors, are located in the deep fascia and
      activated when movement are performed. Increased viscosity of the deep fascia and
      muscles due to increased viscosity of hyaluronic acid (HA) molecules prevents the
      normal gliding of fascia during movement inhibiting normal proprioception and
      muscle function.

PMID- 28750981
TI  - Interexaminer reliability study of a standardized myofascial diagnostic technique
      of the superior thoracic inlet.
AB  - Regional fascial motion palpation is often incorporated by osteopathic
      practitioners to enable them to identify superior thoracic inlet (STI) myofascial
      somatic dysfunction motion patterns; however without standardized instruction,
      diagnostic outcomes may vary between examiners. This study proposes a protocol
      for diagnosing the STI motion pattern that standardizes examiner hand placement,
      palpatory discrimination, posture, and relative body positioning. The study
      design incorporated useful infrastructure recommended by the Federation
      Internationale de Medecine Manuelle (FIMM) including protocol agreement steps
      prior to conducting the formal interexaminer reliability study with the goals of
      attaining >80% interexaminer agreement and kappa values >0.6 for each cardinal
      plane. The agreement phase comprised of testing 52 participants acquired
      agreements of 92.3% (rotation), 88.9% (translation), and 94.2% (sagittal). Kappa
      value testing involving an additional 82 participants obtained values of 0.65
      (rotation), 0.59 (translation), and 0.70 (sagittal). Such kappa values endorse
      fair-to-excellent positive interexaminer correlations, demonstrating utility of
      this standardized palpatory protocol for STI myofascial dysfunctional diagnosis.

PMID- 28750982
TI  - The significance of closed kinematic chains to biological movement and dynamic
      stability.
AB  - Closed kinematic chains (CKCs) are widely used in mechanical engineering because
      they provide a simple and efficient mechanism with multiple applications, but
      they are much less appreciated in living tissues. Biomechanical research has been
      dominated by the use of lever models and their kinematic analysis, which has
      largely ignored the geometric organization of these ubiquitous and evolutionary
      conserved systems, yet CKCs contribute substantially to our understanding of
      biological motion. Closed-chain kinematics couple multiple parts into continuous
      mechanical loops that allow the structure itself to regulate complex movements,
      and are described in a wide variety of different organisms, including humans. In
      a biological context, CKCs are modular units nested within others at multiple
      size scales as part of an integrated movement system that extends throughout the
      organism and can act in synergy with the nervous system, where present. They
      provide an energy-efficient mechanism that enables multiple mechanical functions
      to be optimized during embryological development and increases evolutionary
      diversity.

PMID- 28750983
TI  - A critical overview of the current myofascial pain literature - June 2017.
AB  - We would like to welcome Dr. Li-Wei Chou, MD, PhD as our newly appointed
      contributing author. Dr. Chou is Assistant Professor at China Medical University
      in Taichung, Taiwan and he has an impressive publication record with many
      research studies and book chapters. The current overview includes several
      articles comparing dry needling (DN) to acupuncture with sharply contrasting
      points of view. Several basic studies shed further light on the nature of
      myofascial pain, myalgia, fascia and examination techniques, such as
      sonoelastography. Neuroimaging studies demonstrated microstructural abnormalities
      in brain gray matter of chronic myofascial pain patients, which is an important
      new finding. As usual, many manual TrP papers and DN papers were published in the
      past several months.

PMID- 28750984
TI  - A commentary review of the cost effectiveness of manual therapies for neck and
      low back pain.
AB  - BACKGROUND & PURPOSE: Neck and low back pain (NLBP) are global health problems,
      which diminish quality of life and consume vast economic resources. Cost
      effectiveness in healthcare is the minimal amount spent to obtain acceptable
      outcomes. Studies on manual therapies often fail to identify which manual therapy
      intervention or combinations with other interventions is the most cost effective.
      The purpose of this commentary is to sample the dialogue within the literature on
      the cost effectiveness of evidence-based manual therapies with a particular focus
      on the neck and low back regions. METHODS: This commentary identifies and
      presents the available literature on the cost effectiveness of manual therapies
      for NLBP. Key words searched were neck and low back pain, cost effectiveness, and
      manual therapy to select evidence-based articles. Eight articles were identified
      and presented for discussion. RESULTS: The lack of homogeneity, in the available
      literature, makes difficult any valid comparison among the various cost
      effectiveness studies. DISCUSSION: Potential outcome bias in each study is
      dependent upon the lens through which it is evaluated. If evaluated from a
      societal perspective, the conclusion slants toward "adequate" interventions in an
      effort to decrease costs rather than toward the most efficacious interventions
      with the best outcomes. When cost data are assessed according to a healthcare (or
      individual) perspective, greater value is placed on quality of life, the
      patient's beliefs, and the "willingness to pay."

PMID- 28750985
TI  - The use of Neuro-Ultrasound to identify and treat nerve pathology.

PMID- 28750986
TI  - Intra-rater and inter-rater reliability of total faulty breathing scale using
      visual observation and videogrammetry methods.
AB  - Faulty breathing is an aspect of alteration in the normal fundamental pattern of
      breathing. The available existence of scales in assessing faulty breathing has
      not frequently been used. Measurement errors in assessing and quantifying
      breathing patterns may originate from unclear directions and variation between
      observers. This study determined the measure reliability of the Total Faulty
      Breathing Scale (TFBS) for quantifying breathing patterns. Twenty seven
      participants were recruited comprising healthy and unhealthy subjects. Two
      examiners assessed their breathing patterns using the TFBS on two different
      occasions with visual observation and a videogrammetry method. Evaluation of the
      observational breathing pattern method for intra-rater and inter-rater showed
      agreement of 96.30% and a kappa score of greater than 0.78, which indicated
      substantial agreements. The videogrammetry method showed a percent agreement of
      (100%) with a kappa score of (1.00). This study indicates that the TFBS is a
      considerably reliable tool for evaluating breathing patterns with both visual
      observation and a videogrammetry method.

PMID- 28750987
TI  - Evaluation of knee range of motion: Correlation between measurements using a
      universal goniometer and a smartphone goniometric application.
AB  - BACKGROUND: Goniometers are commonly used to measure range of motion in the
      musculoskeletal system. Recently smartphone goniometry applications have become
      available to clinicians. OBJECTIVE: Compare angular measures using a universal
      goniometer and a smartphone application. METHODS: Thirty four healthy women with
      at least 20 degrees  of limited range of motion regarding knee extension were
      recruited. Knee flexion angles of the dominant limb were measured with a
      universal goniometer and the ROM(c) goniometric application for the smartphone.
      Three trained examiners compared the two assessment tools. RESULTS: Strong
      correlations were found between the measures of the universal goniometer and
      smartphone application (Pearson's correlation and interclass correlation
      coefficient > 0.93). The measurements with both devices demonstrated low
      dispersion and little variation. CONCLUSION: Measurements obtained using the
      smartphone goniometric application analyzed are as reliable as those of a
      universal goniometer. This application is therefore a useful tool for the
      evaluation of knee range of motion.

PMID- 28750988
TI  - Reliability of digital photography for assessing lower extremity alignment in
      individuals with flatfeet and normal feet types.
AB  - AIM: The aim of this study was to investigate the intratester reliability of
      digital photographic method for quantifying static lower extremity alignment in
      individuals with flatfeet and normal feet types. METHODS: Thirteen females with
      flexible flatfeet and nine females with normal feet types were recruited from
      university communities. Reflective markers were attached over the participant's
      body landmarks. Frontal and sagittal plane photographs were taken while the
      participants were in a standardized standing position. The markers were removed
      and after 30 min the same procedure was repeated. Pelvic angle, quadriceps angle,
      tibiofemoral angle, genu recurvatum, femur length and tibia length were measured
      from photographs using the Image j software. RESULTS: All measured variables
      demonstrated good to excellent intratester reliability using digital photography
      in both flatfeet (ICC: 0.79-0.93) and normal feet type (ICC: 0.84-0.97) groups.
      CONCLUSION: The findings of the current study indicate that digital photography
      is a highly reliable method of measurement for assessing lower extremity
      alignment in both flatfeet and normal feet type groups.

PMID- 28750989
TI  - Reliability of SEMG measurements for trunk muscles during lifting variable loads
      in healthy subjects.
AB  - OBJECTIVE: The reliability of surface electromyography (SEMG) derived parameters
      is of high importance, but there is distinct lack of studies concerning the
      reliability during dynamic contractions. Particularly, the similarity index
      reliability has not been investigated during functional task yet. The purpose of
      this study was to evaluate the reliability of trunk muscle activities measured by
      means of surface electromyography during lifting tasks over repeated trials
      within a day. METHODS: Seven volunteers were assessed twice a day. SEMG signals
      were recorded bilaterally from seven trunk muscles. Intra class correlation
      coefficients (ICC) and standard error of similarity index, magnitude and timing
      were calculated. RESULTS: Investigation of ICC and correlation between trials
      showed that similarity index (ICC 0.73-0.97, correlation 0.6-0.95) is more
      reliable and repeatable than muscles magnitude (ICC 0.41-0.69, correlation 0.54
      0.65) and it's timing (ICC 0.41-0.69, correlation 0.31-0.74) while timing had the
      least reliability. CONCLUSION: Similarity index can be mentioned as an
      appropriate motor control index and evaluation of muscle recruitment pattern
      should be done by considering similarity index and magnitude.

PMID- 28750990
TI  - A comparison of scapulothoracic muscle electromyographic activity in subjects
      with and without subacromial impingement syndrome during a functional task.
AB  - Shoulder impingement syndrome (SIS) is the common cause of shoulder pain and
      disability and the individuals suffering from it are usually in different levels
      of physical activity covering an extensive age range. In spite of limited
      scientific evidence for an altered motor pattern in the shoulder muscles of
      patients with SIS, they are frequently referred to physiotherapists in an attempt
      to optimize coordination and strength of the affected muscles. The aim of this
      study was to compare scapular muscle activity in a general population of subjects
      with and without SIS during an arm elevation task executed at different speeds in
      two load conditions. The study is that of a comparative observational using a
      simple convenience sampling method, comprising 8 females (31.63 +/- 9.39) with
      SIS and 10 females (29.10 +/- 6.57) without SIS, matched in terms of age, body
      mass index (BMI) and levels of physical activity. The surface EMG (SEMG) of all
      the trapezius muscles, i.e., -upper fibers (UT), middle fibers (MT), and lower
      fibers (LT) serratus anterior (SA), and middle deltoid were recorded during
      shoulder elevation in a scapular plane at three speeds (slow, moderate, and fast)
      and two load conditions (with and without load). Data were analyzed using
      independent t-tests and three-factor repeated measures analysis of variance and
      Bonferroni method for paired comparisons. The EMG tests results in muscle
      activities revealed no significant differences between the two groups at three
      speeds, and with and without load. The findings do not support the claim that SIS
      necessarily accompanies changes in scapula thoracic and glenohumeral muscle
      activity.

PMID- 28750991
TI  - The Movement movement.

PMID- 28750992
TI  - Adapting to floor sitting and kneeling.
AB  - This short practical article suggests that for those unused to ground living,
      increasing their time spent in sitting or kneeling postures may improve their
      adaptation of their passive and active joint structures by using low stools,
      mats, blocks, yoga bricks, bolsters/cushions, and rolled towels. A very slow
      approach to adaptation and a deliberate reduction of extremes of available lower
      limb joint range, in the beginning of the process, is likely to reduce possible
      tissue overload injury risk.

PMID- 28750993
TI  - The Kettlebell Arm Bar.

PMID- 28750994
TI  - Inter-rater and intra-rater reliability of a movement control test in shoulder.
AB  - BACKGROUND: Movement faults are commonly observed in patients with
      musculoskeletal pain. The Kinetic Medial Rotation Test (KMRT) is a movement
      control test used to identify movement faults of the scapula and gleno-humeral
      joints during arm movement. Objective tests such as the KMRT need to be reliable
      and valid for the results to be applied across different clinical settings and
      patient populations. The primary objective of the present study was to determine
      the intra-rater and inter-rater reliability of KMRT in subjects with and without
      shoulder pain. METHODS: Sixty subjects were included in this study based on
      specific inclusion and exclusion criteria. Two musculoskeletal physiotherapists
      with different levels of clinical experience performed the tests. The intra-rater
      reliability was tested in twenty asymptomatic subjects by a single assessor at
      two week intervals. An equal number of subjects with and without shoulder pain
      were tested by both the assessors to determine the inter-rater reliability. Both
      components of the KMRT, the Gleno- Humeral Anterior Translation (GHAT) and the
      Scapular Forward Tilt (SCFT) were tested. RESULTS: The Kappa values for inter
      rater reliability of the GHAT and SCFT were K = 0.68 & K = 0.65 respectively in
      subjects with shoulder pain. In asymptomatic subjects, the inter-rater
      reliability of GHAT was K = 0.61 and SCFT was K = 0.85. Intra-rater reliability
      ranged from K = 0.66 for GHAT to K = 0.87 for SCFT. CONCLUSION: Our study found
      substantial agreement in inter-rater reliability of KMRT in subjects with
      shoulder pain, whereas substantial to near perfect agreement was found in intra
      rater and inter-rater reliability of KMRT in subjects without shoulder pain.

PMID- 28750995
TI  - Effect of stretching of piriformis and iliopsoas in coccydynia.
AB  - : Pain in the coccyx is referred as coccydynia. The pain aggravates in weight
      bearing i.e. sitting. Total 48 persons with coccydynia diagnosed clinically were
      recruited and randomly assigned into one of the 3 groups. Experimental group I
      were treated by stretching of piriformis and iliopsoas muscles, experimental
      group II were treated by stretching of piriformis and iliopsoas muscles and
      Maitland's rhythmic oscillatory thoracic mobilization over the hypomobile
      segments and the conventional group were treated by seat cushioning + Sitz bath +
      Phonophorosis. All participants underwent an initial baseline assessment for
      Pressure Pain Threshold (PPT) by using modified syringe algometer and pain free
      sitting duration. All the subjects were advised to minimise sitting posture and
      use a seat cushion. Treatment was given for 3 weeks, 5 sessions per week and post
      treatment evaluation was done after completion of 3 weeks. Follow up evaluation
      was done after 1 month. DATA ANALYSIS: The data was analyzed by using 3 * 3
      ANOVA. Tukey's HSD post-Hoc analysis was used for all pair wise comparison.
      RESULTS: The overall results of the study showed that there was significant
      improvement in pain pressure threshold and pain free sitting in both the
      experimental groups with treatment and improvement continued after cessation of
      therapy, whereas the conventional group did not improve significantly.

PMID- 28750996
TI  - Corrigendum to "The effects of 12 weeks Pilates-inspired exercise training on
      functional performance in older women: A randomized clinical trial" [J. Bodyw.
      Mov. Ther. 21 (2017) 251-258].

PMID- 28750997
TI  - [Atrial functional mitral regurgitation. Three-dimensional echocardiographic
      study].
AB  - INTRODUCTION AND OBJECTIVES: Atrial fibrillation can lead to left atrium
      remodelling and induce functional mitral regurgitation. The aim of this study is
      to establish those features of the mitral annulus that are related to atrial
      functional mitral regurgitation. METHODS: A total of 29 patients with persistent
      atrial fibrillation and 36 controls in sinus rhythm were retrospectively
      enrolled. The characteristics of the mitral annulus were analysed by three
      dimensional transoesophageal echocardiography in both groups. The 2D and 3D
      echocardiographic parameters were correlated with the effective regurgitant
      orifice. RESULTS: Patients with atrial fibrillation had a larger left atrium
      volume, anteroposterior diameter at end-diastole, and lower percentage of change
      in this diameter (P=.015, P=.019 and P<.001, respectively). In the multiple
      regression analysis, the ellipticity index (beta: -0.756, P=.004) and height
      anterolateral-posteromedial diameter ratio (beta: -0704, P=.003) were independent
      parameters that correlated with the effective regurgitant orifice (R2: 0.699,
      P=.019) in patients with atrial fibrillation. CONCLUSIONS: Atrial fibrillation
      leads to atrial dilation and alterations in the size and dynamics of the
      anteroposterior diameter, producing a circular mitral annulus. The independent
      determining factors of atrial functional mitral regurgitation in the atrial
      fibrillation group were the ellipticity index and the height-anterolateral
      posteromedial diameter ratio.

PMID- 28750998
TI  - The alternative splicing of BdTai and its involvement in the development of
      Bactrocera dorsalis (Hendel).
AB  - Interest in insect metamorphosis has primarily focused on juvenile hormone (JH)
      and ecdysone. Compared to ecdysone signaling, the molecular action of JH is less
      well established because Methoprene-tolerant (Met) as the JH receptor has been
      identified until recently. In vitro studies have indicated that Met forms an
      active JH-dependent complex with one partner protein, Taiman (Tai). However, the
      related studies on Tai's role in insect metamorphosis are very limited. In this
      study, five Tai isoforms differing in C-terminal region are identified from the
      oriental fruit fly Bactrocera dorsalis, an important worldwide pest infesting
      fruits and vegetables. The spatiotemporal expression pattern analysis indicates
      that BdTai-A and BdTai-B are highly expressed in early larvae while BdTai-D is
      more abundant in middle-late larvae. Meanwhile, in vivo methoprene stress leads
      to dramatic expression pattern fluctuation of BdTai isoforms. The subsequent
      reverse genetic study reveal that all Tai isoforms (denoted as "Tai-core")
      depletion in larvae stage of B. dorsalis produce precocious larvae-pupae
      development, i.e. shortened pupation process and miniature pupae. Further
      knockdown of individual Tai isoform show that silence of BdTai-E causes the same
      phenotype as of BdTai-core RNAi. The current data suggest that BdTai-E is
      involved in transducing the JH signal that represses metamorphosis. Besides,
      isoforms should be considered when studying Tai functions.

PMID- 28751000
TI  - Linear IgA Bullous Dermatosis Presenting as Toxic Epidermal Necrolysis.

PMID- 28750999
TI  - Pigmentary analysis of eggs of the silkworm Bombyx mori.
AB  - Ommochromes are major pigments involved in coloration of eggs, eyes, wings, and
      epidermis of insects. Bombyx mori (silkworm) eggs contain a mixture of ommochrome
      pigments and their precursors. Here, we analyzed the pigment composition of every
      egg color strain using egg color mutants (w-2, pe, and re) and wild-type strains
      (dazao and C108) by using full wavelength scanning and high-performance liquid
      chromatography. We identified ommochrome pigments and their precursors in pigment
      extracts from non-diapause eggs and diapause eggs, and found that the quantities
      of ommochrome precursor 3-hydroxy-kynurenine were much higher in the diapause
      eggs. Ommochrome pigments were absent in the non-diapause eggs. We analyzed the
      pigment composition of every egg color strain and found an accumulation of 3
      hydroxy-kynurenine and absence of ommochromes in the yellow eggs (w-2 and pe),
      suggesting that the essential factors for ommochrome biosynthesis are high levels
      of 3-hydroxy-kynurenine, enzymes for ommochrome synthesis and transferase, and
      spermatiation. Moreover, we confirmed that both decarboxylated xanthommatin and
      xanthommatin are major ommochrome pigments, and the quantity of decarboxylated
      xanthommatin is much higher than that of xanthommatin in silkworm eggs. Since
      ommochrome pigments can change color under oxidative/reductive conditions and the
      egg color mutant re turns crimson when preserved at a low temperature for a few
      weeks, we used an oxidation-reduction reaction in vitro to explore mechanisms
      behind the pigment-based color change. Specifically, during diapause, the
      contents of decarboxylated xanthommatin and xanthommatin are increased, and the
      ommochrome pigments convert into their reduced forms.

PMID- 28751001
TI  - Effect of tofacitinib on lipid levels and lipid-related parameters in patients
      with moderate to severe psoriasis.
AB  - BACKGROUND: Psoriasis is a systemic inflammatory disease associated with
      increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is
      an oral Janus kinase inhibitor. OBJECTIVE: The aim of the study was to
      investigate the effects of tofacitinib on traditional and nontraditional lipid
      parameters and CV risk markers in patients with psoriasis from a phase III study,
      OPT Pivotal 1. METHODS: Patients with psoriasis were randomized to tofacitinib 5
      or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at
      baseline, week 4, and week 16. Analyses included serum cholesterol levels,
      triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk
      markers, and high-density lipoprotein (HDL) function analyses. RESULTS: At week
      16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL
      C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total
      cholesterol/HDL-C ratio did not change. There was no significant change in the
      number of small dense LDL particles, which are considered to be more atherogenic
      than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity,
      linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid
      A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity
      to promote cholesterol efflux from macrophages did not change. Lecithin
      cholesterol acyltransferase activity, which is associated with reverse
      cholesterol transport, increased. Markers of systemic inflammation, serum amyloid
      A and C-reactive protein, decreased with tofacitinib. CONCLUSION: While small
      increases in lipid levels are observed with tofacitinib treatment in patients
      with psoriasis, effects on selected lipid-related parameters and other
      circulating CV risk biomarkers are not suggestive of an increased CV risk
      [NCT01276639].

PMID- 28751002
TI  - Laparoscopic pediatric inguinal hernia repair: a controlled randomized study.
AB  - BACKGROUND: Inguinal hernia repair is one of the most frequently performed
      surgical procedure in infants and young children. Laparoscopic hernia repair in
      infancy and childhood is still debatable. There are many techniques available for
      laparoscopic hernia repair in pediatrics. The aim of the study is to compare
      laparoscopic intracorporeal purse-string suture ligation of the hernia defect
      leaving the sac intact versus disconnection of the hernia sac with intracorporeal
      suturing of proximal part. PATIENTS AND METHODS: A prospective controlled
      randomized study of laparoscopic repair of congenital inguinal hernia (CIH) was
      conducted over a period of 2years and 8months from April 2014 to December 2016.
      All patients were randomized into two equal groups: Group I (n=66) received
      intracorporeal purse string suture ligation of the hernia sac at internal
      inguinal ring [IIR] leaving the sac intact; and Group II (n=66) received
      disconnection of the hernia sac with intracorporeal suture of proximal part at
      IIR. INCLUSION CRITERIA: Male patient with bilateral CIH, questionable other
      side, cases of CIH associated with umbilical hernia and parental request.
      EXCLUSION CRITERIA: Recurrent cases, complicated cases, hernia of canal of Nuck
      in females, inguinal hernia with undescended testis, parental refusal. The main
      outcome measurements were operative time, postoperative hydrocele formation,
      recurrence rate. RESULTS: This study included 132 patients with 157 hernia
      defects. Their age ranged from 6months to 3years. Statistically significant
      differences regarding the demographic data of the groups. All cases were
      completed successfully without conversion. There was no statistically significant
      difference between groups regarding intraoperative complications and hospital
      stay. There was statistically significant difference in the operative time and
      post-operative complications between the studied groups. CONCLUSIONS:
      Laparoscopic inguinal hernia repair by disconnection of the hernia sac at the IIR
      with peritoneal closure is safe and feasible method. It has a lower recurrence
      rate than the purse string suturing leaving the sac intact.

PMID- 28751003
TI  - Follow-up of children or teenagers with paroxysmal supraventricular tachycardia,
      but without pre-excitation syndrome.
AB  - BACKGROUND: Paroxysmal supraventricular tachycardia (SVT) is considered benign in
      children if the electrocardiogram in sinus rhythm is normal, but causes anxiety
      in parents, children and doctors. AIMS: To report on the clinical and
      electrophysiological data from children with SVT, their follow-up and management.
      METHODS: Overall, 188 children/teenagers (mean age 15+/-2.8 years) with a normal
      electrocardiogram in sinus rhythm were studied for SVT, and followed for 2.3+/-4
      years. RESULTS: SVT was poorly tolerated in 30/188 children (16.0%). SVT was
      related to atrioventricular nodal reentrant tachycardia (AVNRT) (n=133) or
      atrioventricular reentrant tachycardia (AVRT) over a concealed accessory pathway
      (n=55; 29.3%). Ablation of the slow pathway (n=66) or the accessory pathway
      (n=43) was performed without general anaesthesia, 2+/-3 years after initial
      evaluation. Failure or refusal to continue occurred in 18/109 (16.5%) children:
      7/66 with AVNRT (10.6%), 11/43 with AVRT (25.6%) (P<0.001). Symptoms of SVT
      recurred in 20/91 children (22.0%) with apparently successful ablation: 6/91
      (6.6%) had real SVT recurrence; 14/91 (15.4%) had only a sinus tachycardia, more
      frequent in AVNRT (11/59; 18.6%) than AVRT (3/32; 9.4%) (P<0.05). In 13 children
      treated with an antiarrhythmic drug (AAD), SVT recurred in four; two presented
      AAD-related syncope. In 66 untreated children, one death was noted after
      excessive AAD infusion to stop SVT; the others remained asymptomatic or had well
      tolerated SVT. CONCLUSIONS: At the time of ablation, SVT management remains
      difficult in children. Indications for ablation are more common in AVRT than in
      AVNRT, but failures are frequent; 22.0% remained symptomatic after successful
      ablation, but false recurrences were frequent (15.4%). Without ablation, one
      third had a spontaneous favourable evolution.

PMID- 28751004
TI  - Polyphenols activate energy sensing network in insulin resistant models.
AB  - Unhealthy diet deficient in fruits and vegetables but rich in calories is
      considered to be one factor responsible for the increased prevalence of insulin
      resistance and type 2 diabetes (T2D). The consumption of fast foods and soft
      drinks increases fructose consumption per se and this is of major concern since
      prolonged fructose intake induces insulin resistance and thereby T2D. The energy
      homeostasis is regulated by a network consisting of "fuel gauze" called AMP
      activated protein kinase (AMPK), the NAD+ dependent type III deacetylase (SIRT1)
      and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC
      1alpha) which is disrupted in T2D. The present study was aimed to investigate the
      action of naringenin and quercetin on energy sensing molecules in insulin
      resistant models. L6 myotubes and albino Wistar rats were rendered insulin
      resistant with palmitate and fructose respectively. Naringenin, quercetin or
      metformin were used for treatment. Fructose and palmitate treatment resulted in
      insulin resistance as evidenced by decreased glucose transporter 4 (GLUT4)
      translocation. The translocation of GLUT4, phosphorylation of AMPK and the
      expression of SIRT1 and PGC-1alpha which were reduced in insulin resistant cells,
      were increased upon treatment with polyphenols. Further, naringenin and quercetin
      showed binding affinity with energy sensing molecules. We conclude that drugs
      from natural resources that target energy sensing molecules might be helpful to
      prevent insulin resistance.

PMID- 28751005
TI  - Corrigendum to "Pyrene-based chemosensor detects picric acid upto attogram level
      through aggregation enhanced excimer emission" [Anal. Chim. Acta 864 (2015) 55
      63].

PMID- 28751008
TI  - Molecular epidemiology of Bordetella pertussis in Cambodia determined by direct
      genotyping of clinical specimens.
AB  - OBJECTIVES: This study sought to determine the genotypes of circulating
      Bordetella pertussis, the causative agent of pertussis, in Cambodia by direct
      molecular typing of clinical specimens. METHODS: DNA extracts from nasopharyngeal
      swabs obtained from 82 pertussis patients in 2008-2016 were analyzed by
      multilocus variable-number tandem repeat analysis (MLVA). B. pertussis virulence
      associated allelic genes (ptxA, prn, and fim3) and the pertussis toxin promoter
      ptxP were also investigated by DNA sequence-based typing. RESULTS: Forty-four DNA
      extracts (54%) yielded a complete MLVA profile, and these were sorted into 8 MLVA
      types (MT18, MT26, MT27, MT29, MT43, MT72, MT95, and MT200). MT27 and MT29, which
      are common in developed countries, were the predominant strain types (total 73%).
      The predominant profile of virulence-associated allelic genes was the combination
      of ptxP3/ptxA1/prn2/fim3A (48%). MT27 strains were detected during the entire
      study period, whereas MT29 strains were only found in 2014-2016. CONCLUSIONS: The
      B. pertussis population in Cambodia, where a whole-cell pertussis vaccine (WCV)
      has been continuously used, resembled those observed previously in developed
      countries where acellular pertussis vaccines are used. Circulating B. pertussis
      strains in Cambodia were distinct from those in other countries using WCVs.

PMID- 28751009
TI  - Mucormycosis infection in the upper limb: a salvageable condition.

PMID- 28751006
TI  - Apolipoprotein E Promotes Invasion in Oral Squamous Cell Carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) patients generally have a poor prognosis,
      because of the invasive nature of these tumors. In comparing transcription
      profiles between OSCC tumors with a more invasive (worst pattern of tumor
      invasion 5) versus a less invasive (worst pattern of tumor invasion 3) pattern of
      invasion, we identified a total of 97 genes that were overexpressed at least 1.5
      fold in the more invasive tumor subtype. The most functionally relevant genes
      were assessed using in vitro invasion assays with an OSCC cell line (UM-SCC-1).
      Individual siRNA knockdown of 15 of these 45 genes resulted in significant
      reductions in tumor cell invasion compared to a nontargeting siRNA control. One
      gene whose knockdown had a strong effect on invasion corresponded to
      apolipoprotein E (APOE). Both matrix degradation and the number of mature
      invadopodia were significantly decreased with APOE knockdown. APOE knockdown also
      resulted in increased cellular cholesterol, consistent with APOE's role in
      regulating cholesterol efflux. APOE knockdown resulted in decreased levels of
      phospho-extracellular signal-regulated kinase 1/2, phospho-c-Jun N-terminal
      kinase, and phospho-cJun, as well as decreased activator protein 1 (AP-1)
      activity. Expression of matrix metalloproteinase 7 (MMP7), an AP-1 target, was
      also significantly decreased. Our findings suggest that APOE protein plays a
      significant role in OSCC tumor invasion because of its effects on cellular
      cholesterol and subsequent effects on cell signaling and AP-1 activity, leading
      to changes in the expression of invasion-related proteins, including MMP7.

PMID- 28751010
TI  - Incidence, risk factors, and outcome of multidrug-resistant Acinetobacter
      baumannii acquisition during an outbreak in a burns unit.
AB  - BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MR-AB) can cause
      outbreaks in a burns unit. AIM: To study the incidence, risk factors and outcome
      of MR-AB colonization during an outbreak. METHODS: A prospective study was
      conducted from April to November 2014 in a burns unit in Paris. Weekly
      surveillance cultures of patients and their environment were performed. MR-AB
      acquisition, discharge, or death without MR-AB colonization were considered as
      competing events. To identify risk factors for colonization, baseline
      characteristics and time-dependent variables were investigated in univariate and
      multivariate analyses using Cox models. MR-AB strains were genotypically compared
      using multi-locus sequence typing. FINDINGS: Eighty-six patients were admitted in
      the burns unit during the study period. Among 77 patients without MR-AB
      colonization at admission, 25 (32%) acquired MR-AB with a cumulative incidence of
      30% at 28 days (95% CI: 20-40). Median time to MR-AB acquisition was 13 days
      (range: 5-34). In multivariate analysis, risk factors for MR-AB acquisition were
      >=2 skin graft procedures performed [hazard ratio (HR): 2.97; 95% confidence
      interval (CI): 1.10-8.00; P = 0.032] and antibiotic therapy during
      hospitalization (HR: 4.42; 95% CI: 1.19-16.4; P = 0.026). A major sequence type
      of MR-AB (ST2) was found in 94% and 92% of patients and environmental strains,
      respectively, with all strains harbouring the blaOXA-23 gene. MR-AB colonization
      increased length of hospitalization (HR: 0.32; 95% CI: 0.17-0.58; P = 0.0002) by
      a median of 12 days. CONCLUSION: A high incidence of MR-AB acquisition was seen
      during this outbreak with most strains from patients and their environment
      belonging to single sequence type. MR-AB colonization was associated with more
      skin graft procedures, antibiotic use, and prolonged hospitalization.

PMID- 28751011
TI  - A coupled mitral valve-left ventricle model with fluid-structure interaction.
AB  - Understanding the interaction between the valves and walls of the heart is
      important in assessing and subsequently treating heart dysfunction. This study
      presents an integrated model of the mitral valve (MV) coupled to the left
      ventricle (LV), with the geometry derived from in vivo clinical magnetic
      resonance images. Numerical simulations using this coupled MV-LV model are
      developed using an immersed boundary/finite element method. The model
      incorporates detailed valvular features, left ventricular contraction, nonlinear
      soft tissue mechanics, and fluid-mediated interactions between the MV and LV
      wall. We use the model to simulate cardiac function from diastole to systole.
      Numerically predicted LV pump function agrees well with in vivo data of the
      imaged healthy volunteer, including the peak aortic flow rate, the systolic
      ejection duration, and the LV ejection fraction. In vivo MV dynamics are
      qualitatively captured. We further demonstrate that the diastolic filling
      pressure increases significantly with impaired myocardial active relaxation to
      maintain a normal cardiac output. This is consistent with clinical observations.
      The coupled model has the potential to advance our fundamental knowledge of
      mechanisms underlying MV-LV interaction, and help in risk stratification and
      optimisation of therapies for heart diseases.

PMID- 28751012
TI  - The J to T-peak interval as a biomarker in drug safety studies: A method of
      accuracy assessment applied to two algorithms.
AB  - OBJECTIVES: To evaluate performance of J-to-T-peak (JTP) measurements of 12-lead
      ECGs, in a five-arm study using drugs with various levels of electrolyte channel
      block. METHODS: The novel evaluation method distinguishes between different
      aspects of measurement. "Random noise" is the variability among repeated
      measurements made without changing the conditions. "Context noise" is the
      variability of changes in context of the measurement, e.g. T-wave morphology,
      autonomic nervous system state. RESULTS: The average random noise of our RR
      corrected JTPc measurements in standard deviations was 3.0 ms and not dependent
      on the drug. The average context noise was 4.0 ms for ranolazine, verapamil, and
      placebo, and 8.8 ms for dofetilide and quinidine. Measurement consistency is
      corroborated by linear fit confidence intervals of baseline- and placebo
      corrected JTPc versus drug concentration. CONCLUSIONS: Systematic differences
      were found in JTPc drug response between the Mortara method and published data.
      Residual signal component in the context noise may influence future study design.

PMID- 28751013
TI  - Termination of a long RP supraventricular tachycardia by carotid sinus massage.
AB  - Carotid sinus massage is a useful diagnostic and therapeutic maneuver in patients
      with supraventricular tachycardia. Abrupt tachycardia termination with carotid
      sinus massage typically indicates a mechanism dependent on the atrioventricular
      node. Here, we present the case of a 79-year-old patient presenting with a long
      RP supraventricular tachycardia terminated with carotid sinus massage that was
      proven invasively to be due to a focal atrial tachycardia. We discuss mechanistic
      explanations for this unusual phenomenon and review the literature.

PMID- 28751014
TI  - Disappearance of pathologic anteroseptal Q waves after reperfusion with
      percutaneous coronary intervention (PCI) in a 61 year old female: A case report.
AB  - We report a case of a 61 year old female with disappearance of anteroseptal Q
      waves following an anterior STEMI. At presentation a 12 lead ECG revealed frank
      anteroseptal Q waves and T wave inversion (V1-V3). The patient underwent
      percutaneous coronary intervention (PCI) with drug eluting stenting to a
      critically stenosed left anterior descending artery. At a five month follow-up
      visit a 12 lead ECG demonstrated the complete resolution of anteroseptal Q waves
      and normal R wave progression was seen in the precordial leads. Here we discuss
      this observation with a review of the literature regarding Q wave resolution.

PMID- 28751015
TI  - Sacral Neuromodulation is Preferred over OnabotulinumtoxinA Injection for
      Overactive Bladder in Women: Pro.

PMID- 28751016
TI  - Sacral Neuromodulation is Preferred over OnabotulinumtoxinA Injection for
      Overactive Bladder in Women: Con.

PMID- 28751017
TI  - Co-refolding of a functional complex of Dengue NS3 protease and NS2B co-factor
      domain and backbone resonance assignment by solution NMR.
AB  - A novel approach for separate expression of dengue virus NS3 protease and its
      NS2B cofactor domain is described in this paper. The two proteins are expressed
      in E.coli and purified separately and subsequently efficiently co-refolded to
      form a stable complex. This straightforward and robust method allows for separate
      isotope labeling of the two proteins, facilitating analysis by nuclear magnetic
      resonance (NMR) spectroscopy. Unlinked NS2B-NS3pro behaves better in NMR
      spectroscopy than linked NS2B-NS3pro, which has resulted in the backbone
      resonance assignment of the unlinked NS2B-NS3 complex bound to a peptidic boronic
      acid inhibitor.

PMID- 28751018
TI  - Deletion of the P2X4 receptor is neuroprotective acutely, but induces a
      depressive phenotype during recovery from ischemic stroke.
AB  - INTRODUCTION: Acute ischemic injury leads to severe neuronal loss. One of the key
      mechanisms responsible for this effect is inflammation, which is characterized by
      the activation of myeloid cells, including resident microglia and infiltrating
      monocytes/macrophages. P2X4 receptors (P2X4Rs) present on these immune cells
      modulate the inflammatory response. For example, excessive release of adenosine
      triphosphate during acute ischemic stroke triggers stimulation of P2X4Rs, leading
      to myeloid cell activation and proliferation and further exacerbating post
      ischemic inflammation. In contrast, during recovery P2X4Rs activation on
      microglia leads to the release of brain-derived neurotrophic factor (BDNF), which
      alleviate depression, maintain synaptic plasticity and hasten post-stroke
      behavioral recovery. Therefore, we hypothesized that deletion of the P2X4R
      specifically from myeloid cells would have differential effects on acute versus
      chronic recovery following stroke. METHODS: We subjected global or myeloid
      specific (MS) P2X4R knock-out (KO) mice and wild-type littermates of both sexes
      to right middle cerebral artery occlusion (60min). We performed histological,
      behavioral (sensorimotor and depressive), and biochemical (quantitative PCR and
      flow cytometry) analyses to determine the acute (three days after occlusion) and
      chronic (30days after occlusion) effects of receptor deletion. RESULTS: Global
      P2X4R deletion led to reduced infarct size in both sexes. In MS P2X4R KO mice,
      only females showed reduced infarct size, an effect that did not change with
      ovariectomy. MS P2X4R KO mice of both sexes showed swift recovery from
      sensorimotor deficits during acute recovery but exhibited a more pronounced post
      stroke depressive behavior phenotype that was independent of infarct size.
      Quantitative PCR analysis of whole cell lysate as well as flow-sorted myeloid
      cells from the perilesional cortex showed increased cellular interleukin 1 beta
      (IL-1beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha)
      mRNA levels but reduced plasma levels of these cytokines in MS P2X4R KO mice
      after stroke. The expression levels of BDNF and other depression-associated genes
      were reduced in MS P2X4R KO mice after stroke. CONCLUSIONS: P2X4R deletion
      protects against stroke acutely but predisposes to depression-like behavior
      chronically after stroke. Thus, a time-sensitive approach should be considered
      when targeting P2X4Rs after stroke.

PMID- 28751019
TI  - The cystathionine beta-synthase/hydrogen sulfide pathway contributes to microglia
      mediated neuroinflammation following cerebral ischemia.
AB  - The mechanisms underlying neuroinflammation following cerebral ischemia remain
      unclear. Hydrogen sulfide (H2S), a newly identified gasotransmitter, has been
      reported to regulate inflammation. In the current study, we investigated whether
      the endogenous H2S production pathway contributed to microglia-mediated
      neuroinflammation following stroke. We used a mouse middle cerebral artery
      occlusion (MCAO) model and an in vitro cellular model to mimic ischemia-induced
      microglial neuroinflammation. Expression of the H2S synthase cystathionine beta
      synthase (CBS) and H2S synthetic activity were rapidly decreased in the ischemic
      brain tissue following MCAO. Consistently, when cultured microglia were polarized
      toward a pro-inflammatory phenotype with conditioned medium collected from
      neurons that had been subjected to oxygen-glucose deprivation (OGD neuron CM),
      they displayed reduced CBS expression and H2S production. Enhancing H2S
      bioavailability either by overexpressing CBS or by supplementing with exogenous
      H2S donors promoted a shift in microglial polarization from ischemia-induced pro
      inflammatory phenotypes toward anti-inflammatory phenotypes. Mechanistically,
      microglia that were exposed to OGD neuron CM displayed reduced activation of AMP
      activated protein kinase (AMPK), which was rescued by overexpressing CBS or by
      supplementing with H2S donors. Moreover, the promoting effects of H2S donors on
      microglial anti-inflammatory polarization were abolished by an AMPK inhibitor or
      CaMKKbeta inhibitor. Our results suggested that reduced CBS-H2S-AMPK cascade
      activity contributed to microglia-mediated neuroinflammation following stroke.
      Targeting the CBS-H2S pathway is a promising therapeutic approach for ischemic
      stroke.

PMID- 28751020
TI  - Nuclear deterrents: Intrinsic regulators of IL-1beta-induced effects on
      hippocampal neurogenesis.
AB  - Hippocampal neurogenesis, the process by which new neurons are born and develop
      into the host circuitry, begins during embryonic development and persists
      throughout adulthood. Over the last decade considerable insights have been made
      into the role of hippocampal neurogenesis in cognitive function and the cellular
      mechanisms behind this process. Additionally, an increasing amount of evidence
      exists on the impact of environmental factors, such as stress and
      neuroinflammation on hippocampal neurogenesis and subsequent impairments in
      cognition. Elevated expression of the pro-inflammatory cytokine interleukin-1beta
      (IL-1beta) in the hippocampus is established as a significant contributor to the
      neuronal demise evident in many neurological and psychiatric disorders and is now
      known to negatively regulate hippocampal neurogenesis. In order to prevent the
      deleterious effects of IL-1beta on neurogenesis it is necessary to identify
      signalling pathways and regulators of neurogenesis within neural progenitor cells
      that can interact with IL-1beta. Nuclear receptors are ligand regulated
      transcription factors that are involved in modulating a large number of cellular
      processes including neurogenesis. In this review we focus on the signalling
      mechanisms of specific nuclear receptors involved in regulating neurogenesis
      (glucocorticoid receptors, peroxisome proliferator activated receptors, estrogen
      receptors, and nuclear receptor subfamily 2 group E member 1 (NR2E1 or TLX)). We
      propose that these nuclear receptors could be targeted to inhibit
      neuroinflammatory signalling pathways associated with IL-1beta. We discuss their
      potential to be therapeutic targets for neuroinflammatory disorders affecting
      hippocampal neurogenesis and associated cognitive function.

PMID- 28751021
TI  - The association between alcohol abuse and neuroendocrine system dysregulation:
      Race differences in a National sample.
AB  - OBJECTIVES: Health outcomes, including chronic disease and mortality, attributed
      to or associated with alcohol abuse are discrepant between African Americans and
      Whites. To date, the topic is not fully understood and few studies conducted have
      used biomarker indicators of health. We investigated whether the association
      between alcohol abuse and biomarkers of the neuroendocrine system vary between
      black or African American and White respondents aged 34-84 from the Midlife in
      the United States Study (MIDUS) II (2004-2006) (n=1129). Alcohol abuse was
      assessed with a modified version of the Michigan Alcohol Screening Test. Ordinary
      least squared (OLS) regression was used to evaluate whether race moderated the
      associations between alcohol abuse and four biomarkers-urinary cortisol and serum
      dehydroepiandrosterone sulfate (DHEA-S), epinephrine and norepinephrine-and two
      composite summary scores, each consisting of two components that characterize the
      hypothalamic pituitary adrenal (HPA)-axis and sympathetic nervous systems (SNS),
      respectively. Covariates included age, sex, education, income, current drinking,
      smoking, exercise, fast food consumption, heart disease, blood pressure,
      diabetes, body mass index, medication use, anxiety/depression, sleep duration,
      and cholesterol markers. Race significantly moderated the associations between
      alcohol abuse and norepinephrine concentration (chi2 [1]=4.48, p=0.034) and the
      SNS composite score (chi2 [1]=5.83, p=0.016). Alcohol abuse was associated with
      higher mean norepinephrine levels (b=0.26, standard error (SE)=0.12, p=0.034) and
      SNS composite score (b=0.23, SE=0.11, p=0.016) for African Americans compared to
      Whites. Interestingly, for Whites a paradoxical association between alcohol
      abuse, norepinephrine and SNS levels was observed; those who abused alcohol had
      lower mean norepinephrine levels than non-abusers. Race differences in
      neuroendocrine response could be biological pathways that contribute the excess
      risk of chronic disease and mortality attributed to alcohol abuse among African
      Americans compared to Whites. Replication of these analyses in larger cohorts are
      warranted in addition to further studies of underlying mechanisms among Blacks
      and Whites separately.

PMID- 28751022
TI  - ER-resident antioxidative GPx7 and GPx8 enzyme isoforms protect insulin-secreting
      INS-1E beta-cells against lipotoxicity by improving the ER antioxidative
      capacity.
AB  - Increased circulating levels of saturated fatty acids (FFAs) and glucose are
      considered to be major mediators of beta-cell dysfunction and death in T2DM.
      Although it has been proposed that endoplasmic reticulum (ER) and oxidative
      stress play a crucial role in gluco/lipotoxicity, their interplay and relative
      contribution to beta-cell dysfunction and apoptosis has not been fully
      elucidated. In addition it is still unclear how palmitate - the physiologically
      most abundant long-chain saturated FFA - elicits ER stress and which immediate
      signals commit beta-cells to apoptosis. To study the underlying mechanisms of
      palmitate-mediated ER stress and beta-cell toxicity, we exploited the observation
      that the recently described ER-resident GPx7 and GPx8 are not expressed in rat
      beta-cells. Expression of GPx7 or GPx8 attenuated FFAs-mediated H2O2 generation,
      ER stress, and apoptosis induction. These results could be confirmed by a H2O2
      specific inactivating ER catalase, indicating that accumulation of H2O2 in the ER
      lumen is critical in FFA-induced ER stress. Furthermore, neither the expression
      of GPx7 nor of GPx8 increased insulin content or facilitated disulfide bond
      formation in insulin-secreting INS-1E cells. Hence, reduction of H2O2 by ER-GPx
      isoforms is not rate-limiting in oxidative protein folding in rat beta-cells.
      These data suggest that FFA-mediated ER stress is partially dependent on
      oxidative stress and selective expression of GPx7 or GPx8 improves the ER
      antioxidative capacity of rat beta-cells without compromising insulin production
      and the oxidative protein folding machinery.

PMID- 28751023
TI  - Lysocardiolipin acyltransferase regulates TGF-beta mediated lung fibroblast
      differentiation.
AB  - Lysocardiolipin acyltransferase (LYCAT), a cardiolipin remodeling enzyme, plays a
      key role in mitochondrial function and vascular development. We previously
      reported that reduced LYCAT mRNA levels in peripheral blood mononuclear cells
      correlated with poor pulmonary function outcomes and decreased survival in IPF
      patients. Further LYCAT overexpression reduced lung fibrosis, and LYCAT knockdown
      accentuated experimental pulmonary fibrosis. NADPH Oxidase 4 (NOX4) expression
      and oxidative stress are known to contribute to lung fibroblast differentiation
      and progression of fibrosis. In this study, we investigated the role of LYCAT in
      TGF-beta mediated differentiation of human lung fibroblasts to myofibroblasts,
      and whether this occurred through mitochondrial superoxide and NOX4 mediated
      hydrogen peroxide (H2O2) generation. Our data indicated that LYCAT expression was
      up-regulated in primary lung fibroblasts isolated from IPF patients and bleomycin
      challenged mice, compared to controls. In vitro, siRNA-mediated SMAD3 depletion
      inhibited TGF-beta stimulated LYCAT expression in human lung fibroblasts. ChIP
      immunoprecipitation assay revealed TGF-beta stimulated SMAD2/3 binding to the
      endogenous LYCAT promoter, and mutation of the SMAD2/3 binding sites (-179/-183
      and -540/-544) reduced TGF-beta-stimulated LYCAT promoter activity.
      Overexpression of LYCAT attenuated TGF-beta-induced mitochondrial and
      intracellular oxidative stress, NOX4 expression and differentiation of human lung
      fibroblasts. Further, pretreatment with Mito-TEMPO, a mitochondrial superoxide
      scavenger, blocked TGF-beta-induced mitochondrial superoxide, NOX4 expression and
      differentiation of human lung fibroblasts. Treatment of human lung fibroblast
      with NOX1/NOX4 inhibitor, GKT137831, also attenuated TGF-beta induced fibroblast
      differentiation and mitochondrial oxidative stress. Collectively, these results
      suggest that LYCAT is a negative regulator of TGF-beta-induced lung fibroblast
      differentiation by modulation of mitochondrial superoxide and NOX4 dependent H2O2
      generation, and this may serve as a potential therapeutic target for human lung
      fibrosis.

PMID- 28751024
TI  - Preoperative pregabalin or gabapentin for acute and chronic postoperative pain
      among patients undergoing breast cancer surgery: A systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND AND OBJECTIVE: Breast cancer surgery is associated with acute and
      chronic pain. We sought to systematically evaluate the effects of gabapentin and
      pregabalin on postoperative pain among patients undergoing breast cancer surgery.
      DATABASES AND DATA TREATMENT: We searched MEDLINE, EMBASE, CENTRAL, Web of
      Science, and ProQuest from the inception of each database to November 2015. We
      included studies enrolling adult patients undergoing breast cancer surgery who
      were randomly assigned to preoperative gabapentin or pregabalin versus placebo or
      active control and assessed acute (<=24 h) or chronic (>=2 months) pain. We
      conducted meta-analyses when possible and rated the quality of evidence (QoE) by
      using the GRADE approach. RESULTS: Twelve studies were eligible for review, of
      which eight evaluated gabapentin (n = 516) and four pregabalin (n = 209).
      Gabapentin reduced pain scores in the recovery room (mean difference [MD] -1.68
      on a 0-10 Numeric Rating Scale (NRS), 95% CI -2.59 to -0.77; minimally important
      difference is 1 point; relative risk [RR] for mild pain (<4/10) 1.71, 95% CI 1.33
      2.02; moderate QoE) and 24 h postoperatively (MD -0.52, 95% CI -1.02 to -0.01; RR
      for mild pain 1.07, 95% CI 1.00-1.13; very low QoE). Pregabalin reduced pain and
      morphine consumption in the recovery room (MD -6.71 mg, 95% CI -10.73 to -2.70;
      low QoE). No significant difference was observed in pain score at 24 h (MD -0.38,
      95%, CI -0.96 to 0.21; moderate QoE). Neither drug reduced the rate of chronic
      postoperative pain. CONCLUSIONS: Gabapentin and pregabalin seem to reduce opioid
      consumption in the recovery room. Gabapentin, but not pregabalin, reduces pain at
      24 h after breast cancer surgery. Neither drug affects the development of chronic
      postoperative pain. SIGNIFICANCE: Gabapentin and pregabalin administered
      perioperatively in patients undergoing breast cancer surgery improve acute
      postoperative pain as indicated by the reduction in opioid consumption. Further
      data are needed on reducing chronic postoperative pain.

PMID- 28751025
TI  - A dual indicator approach for monitoring benthic impacts from organic enrichment
      with test application near Atlantic salmon farms.
AB  - The organic enrichment of surficial sediments has a known effect on benthic
      faunal communities due largely to oxygen depletion and sulfide toxicity. Total
      dissolved sulfide (free S-2=H2S+HS-+S2-) concentrations in sediments are widely
      measured as a practical indicator of community effects. However, the standard ion
      selective electrode (ISE) method for free S-2 analysis can provide biased results
      owing to the inclusion of non-toxic mineral sulfides and the oxidation and
      volatilization of free S-2. A rapid field protocol was developed that alleviates
      these problems while also providing data on dissolved oxygen concentrations.
      Sediments collected near salmon aquaculture pens over cohesive and permeable
      substrates were analysed using the standard and new protocols. The results
      confirm previous conclusions of artifacts with the standard ISE method, while the
      dual indicator approach more accurately describes the stages, spatial extent and
      magnitude of sediment geochemical alterations affecting benthic communities.

PMID- 28751026
TI  - Impact of kelp cultivation on the Ecological Status of benthic habitats and
      Zostera marina seagrass biomass.
AB  - The Ecological Status of subtidal benthic communities within a commercial kelp
      farm on the southwest coast of Ireland was not impacted by macroalgal
      cultivation. Additionally, there was no effect on the biomass of Zostera marina,
      a key habitat under the EU Habitats Directive and OSPAR Commission. However,
      sediment grain size and total organic matter (TOM) were influenced by abiotic and
      biotic aspects of the farm. A temporal effect on univariate and multivariate
      species data, Infaunal Quality Index (IQI) and Z. marina biomass was observed.
      This effect was likely a community response to high storm disturbance in winter
      2013/14. The use of IQI to assess the impact of macroalgal cultivation on benthic
      communities is a novel approach. This study supports a view that environmental
      impacts of macroalgal cultivation are relatively benign compared to other forms
      of aquaculture. Further research must be conducted to understand all interactions
      between aquaculture activities and the environment.

PMID- 28751027
TI  - Settling of dilbit-derived oil-mineral aggregates (OMAs) & transport parameters
      for oil spill modelling.
AB  - The size and settling velocity of oil-mineral aggregates (OMAs) derived from
      diluted bitumen are primary constituents in predictive models for evaluating the
      potential fate of oil spilled in the aquatic environment. A series of low
      sediment concentration (15mg.L-1), colder water (<10 degrees C) wave tank
      experiments designed to measure variability in these parameters in naturally
      formed OMAs in response the presence or absence of chemical dispersant are
      discussed. Corresponding lab experiments revealed settling velocities of
      artificially formed OMAs on the order of 0.1-0.4mm.s-1. High-resolution imagery
      of settling particles were analyzed for particle size, density and settling
      velocity. In situ formation of OMAs in the wave tank was unsuccessful. Possible
      effects of chemical dispersant on natural sediment flocculation, the size of
      suspended oil droplets and clearance rates of suspended particles are discussed.

PMID- 28751028
TI  - Toxic metals biomonitoring based on prey-predator interactions and environmental
      forensics techniques: A study at the Romanian-Ukraine cross border of the Black
      Sea.
AB  - Marine cross-border areas are ideal for monitoring pollutants so as to increase
      ecosystems protection. This study was conducted at the Romanian-Ukraine border of
      the Black Sea to reveal evidence of contamination with toxic metals based on
      biomonitoring of: cadmium, lead, total chromium, nickel and copper at different
      water depths and prey-predator interactions, combined with environmental
      forensics techniques of biological sampling and separation in witnesses size
      groups. The species used were Mytilus galloprovincialis L. and Rapana venosa V.
      collected at 17.5m, 28m and 35m depth. An atomic absorption spectrometer with a
      high-resolution continuum source and graphite furnace was used for toxic metals
      quantification in various samples: sediments, soft tissue, stomach content,
      muscular leg, hepatopancreas. The best sample type, based on the pathology of
      metal location and bioaccumulation, is the hepatopancreas from R. venosa that
      proved a significant decrease of cadmium and lead at lower depths.

PMID- 28751029
TI  - Spatial distribution of marine debris on the seafloor of Moroccan waters.
AB  - Marine debris pollution is considered as a worldwide problem and a direct threat
      to the environment, economy and human health. In this paper, we provide the first
      quantitative assessment of debris on the seafloor of the southern part of the
      economic exclusive waters of Morocco. The data were collected in a scientific
      trawl survey carried out from 5 to 25 October 2014 between (26N) to (21N)
      covering different stratums of depths (from 10 to 266m) and following a sampling
      network of 100 stations distributed randomly in the study area. A total of 603kg
      of debris was collected and sorted into five main categories: plastic, metal,
      rubber, textiles and glass. Over 50% of collected items was made by plastic, 94%
      of them are the plastic fishing gear used to capture the Octopus vulgaris. The
      analysis of the distribution shows that anthropogenic debris is present in the
      majority of the prospected area (~ 47,541km2) with different densities ranging
      from 0 to 1768 (+/- 298,15)kg/km2. The spatial autocorrelation approach using GIS
      shows that the concentration of this debris is correlated very well with a set of
      factors such as the proximity to fishing activity sites. Moreover, the mechanism
      of transportation and dispersion was influenced by the hydrodynamic properties of
      the region.

PMID- 28751030
TI  - Thermal stress exposure, bleaching response, and mortality in the threatened
      coral Acropora palmata.
AB  - Demographic data for Elkhorn coral, Acropora palmata, and in situ water
      temperature data from seven upper Florida Keys (USA) reefs revealed three warm
      thermal stress events between 2010 and 2016. During a mild bleaching event in
      2011, up to 59% of colonies bleached, but no mortality resulted. In both 2014 and
      2015, severe and unprecedented bleaching was observed with up to 100% of colonies
      bleached. A. palmata live tissue cover declined by one-third following the 2014
      2015 events. Colony mortality of mildly- and non-bleached colonies did not differ
      but increased significantly with more severe bleaching. Increased bleaching
      prevalence corresponded to maximum daily average water temperatures above 31.3
      degrees C. However, the cumulative days with daily average exceeding 31.0 degrees
      C provided a better predictor of bleaching response. The bleaching response of
      surviving colonies in 2015 was not consistent with acclimatization as most
      individual colonies bleached at least as badly as in 2014.

PMID- 28751031
TI  - Natural and anthropogenic events influence the soundscapes of four bays on Hawaii
      Island.
AB  - The soundscapes of four bays along the Kona Coast of Hawaii Island were monitored
      between January 2011 and March 2013. Equivalent, unweighted sound pressure levels
      within standard 1/3rd-octave bands (dB re: 1MUPa) were calculated for each
      recording. Sound levels increased at night and were lowest during the daytime
      when spinner dolphins use the bays to rest. A tsunami provided an opportunity to
      monitor the soundscape with little anthropogenic component. We detected a
      decrease in sound levels and variability in one of the busiest bays. During the
      daytime in the 3.15kHz 1/3rd octave band, we detected 92 loud outliers from
      vessels, aquaculture, and military mid-frequency active sonar. During one
      military mid-frequency active sonar event sound levels reached 45.8dB above
      median ambient noise levels. The differences found in the bays illustrate the
      importance of understanding soundscapes to effectively manage noise pollution in
      marine ecosystems.

PMID- 28751032
TI  - Effects of long-term high continuity of care on avoidable hospitalizations of
      chronic obstructive pulmonary disease patients.
AB  - OBJECTIVE: To examine the effects of high continuity of care (COC) maintained for
      a longer time on the risk of avoidable hospitalization of patients with chronic
      obstructive pulmonary disease (COPD). METHODS: A retrospective cohort study
      design was adopted. We used a claim data regarding health care utilization under
      a universal health insurance in Taiwan. We selected 2199 subjects who were newly
      diagnosed with COPD. We considered COPD-related avoidable hospitalizations as
      outcome variables. The continuity of care index (COCI) was used to evaluate COC
      as short- and long-term COC. A logistic regression model was used to control for
      sex, age, low-income status, disease severity, and health status. RESULTS: Long
      term COC had stronger effect on health outcomes than short-term COC did. After
      controlling for covariables, the logistic regression results of short-term COC
      showed that the medium COCI group had a higher risk of avoidable hospitalizations
      (adjusted odds ratio [AOR]: 1.89, 95% CI: 1.07-3.33) than the high COCI group
      did. The results of long-term COC showed that both the medium (AOR: 1.98, 95% CI:
      1.0-3.94) and low (AOR: 2.03, 95% CI: 1.05-3.94) COCI groups had higher risks of
      avoidable hospitalizations than did the high COCI group. CONCLUSIONS: Maintaining
      long-term high COC effectively reduces the risk of avoidable hospitalizations. To
      encourage development of long-term patient-physician relationships could improve
      health outcomes.

PMID- 28751033
TI  - The relationship between health services standardized costs and mortality is non
      linear: Results from a large HMO population.
AB  - Older age, male gender, and poor socioeconomic status have been found to predict
      mortality. Studies have also documented an elevation in health services
      standardized costs (HSSC) and expenditures in the last years of life. We examined
      the contribution of HSSC in the last years of life in predicting mortality beyond
      predictors that have been established in the literature, and whether the impact
      of HSSC on mortality is linear. Vulnerability, operationalized as being exempt
      from co-payments due to poverty, being a holocaust survivor, or other reasons,
      was examined as potentially mediating the relationship between HSSC and
      mortality. We used longitudinal data obtained from the largest Health Maintenance
      Organization in Israel. Subjects were insured persons who were over age 65 in
      2006 (n=423,140). Predictors included demographics, co-morbidity, and HSSC. All
      factors significantly predicted time to death. For HSSC, high levels displayed
      the highest Hazard Ratios (HR), with medium levels having the lowest HRs. The
      higher mortality rate in the low HSSC group might indicate a risk of
      underutilizing health services. Vulnerable status remained a predictor of
      mortality even within a system of universal access to healthcare. There is a need
      for establishing mechanisms to identify those underutilizing health services. A
      universal health care system is insufficient for providing equal health care,
      indicating a need for additional means to increase equality.

PMID- 28751034
TI  - Current concepts on hematopoietic stem cell transplantation outcome registries;
      Emphases on resource requirements for new registries.
AB  - There is tremendous variability in size, scope, and resource requirements for
      registries depending on the number of patients and participating sites. The
      outcome registries are organized systems to collect uniform data using an
      observational study methodology. Patient registries are used to determine
      specified outcomes for a population for predetermined scientific, clinical, or
      policy purposes. Historically, outcome registries established in the development
      of hematopoietic stem cell transplantation (HSCT) have now evolved into myriads
      of locoregional and international transplant activity and outcome resources. Over
      time, these registries have contributed immensely in determining trends,
      patterns, and treatment outcomes in HSCT. There is wider variation in the goals,
      mission, objectives, and outcomes of the ongoing registries depending on the
      organizational structure. There is a growing trend toward overarching
      relationship of these registries to serve as complementary and interoperable
      resources for high potential collaborative research. In addition to capacity
      building, standardized, accredited, and optimally operational registries can
      provide unmatched and unparalleled research data that cannot be obtained
      otherwise. Moving forward, HSCT data collection, collation, and interpretation
      should be an integral part of the treatment rather than an option. Quality
      assurance and continuous quality improvement of the data are pivotal for
      credibility, measurable/quantifiable outcomes, clinically significant impact, and
      setting new benchmarks.

PMID- 28751035
TI  - Risk factors of neurosurgical site infection after craniotomy: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Neurosurgical site infection (SSI) is a complication related to
      craniotomy, which may lead to severe morbidity and higher hospital costs during
      the postoperative period. METHODS: Retrospective cohorts, case-control studies,
      or prospective investigations addressing risk factors of SSI updated until
      January 2017 were systematically searched in 2 databases (PubMed and Embase). The
      Newcastle-Ottawa Scale was used to evaluate quality of the included studies,
      heterogeneity was assessed by I2 tests, and a funnel plot and Egger test were
      used for the evaluation of publication bias. RESULTS: There were 26 studies in
      total enrolled in this review. The results showed that the risk factors which had
      relation with SSI were other infection (odds ratio [OR], 5.42; 95% confidence
      interval [CI], 2.8-10.49), number of operations (>1) (OR, 2.352; 95% CI, 1.142
      4.847), cerebrospinal fluid (CSF) leak (OR, 7.817; 95% CI, 2.573-23.751), CSF
      drainage (OR, 2.55; 95% CI, 1.58-4.11), duration of operation (>4 hours) (as for
      retrospective cohort studies) (OR, 1.766; 95% CI, 1.110-2.809), venous sinus
      entry (OR, 4.015; 95% CI, 1.468-10.982), American Society of Anesthesiologists
      score (>2) (OR, 1.398; 95% CI, 1.098-1.78), sex (male) (as for prospective
      investigations) (OR, 1.474; 95% CI, 1.013-2.145), and surgical reasons
      (nontraumatic) (OR, 2.137; 95% CI, 1.106-4.129). CONCLUSIONS: According to the
      current analysis, all the factors mentioned were the risk factors for SSI after
      craniotomy. Patients with these risk factors should be paid more attention to
      prevent SSI. More evidence provided by high-quality studies is still needed to
      further investigate the risk factors of SSI.

PMID- 28751036
TI  - Characteristics of methicillin-resistant Staphylococcus aureus in patients on
      admission to a teaching hospital in Rio de Janeiro, Brazil.
AB  - BACKGROUND: Infections caused by methicillin-resistant Staphylococcus aureus
      (MRSA) are associated with greater mortality and morbidity; however, risk factors
      for community-acquired infections caused by MRSA have not been established.
      Therefore, community patients who are admitted to hospitals without the necessary
      contact precautions and are infected with community-acquired lineages eventually
      cause these lineages to spread to these settings. The aim of this study was to
      detect community-acquired lineages of MRSA in patients on admission to a
      Brazilian teaching hospital. METHODS: The antimicrobial susceptibility of the
      MRSA isolates from nasal swabs was evaluated as was the molecular characteristics
      of the staphylococcal cassette chromosome mec (SCCmec). The clonality was
      determined using pulsed-field gel electrophoresis and multilocus sequence type
      analysis. RESULTS: A total of 702 patients were evaluated between March 2012 and
      March 2013; 180 (25%) of them were colonized by S aureus, and 21 (3%) were MRSA.
      The SCCmec IV/USA1100/sequence type (ST) 30 was the predominant MRSA lineage
      (42.8%), followed by SCCmec IV/USA800/ST5 (23.8%). CONCLUSIONS: The occurrence of
      MRSA colonization was very low, and only 1 patient from cardiac surgery developed
      an infection, which was caused by an SCCmec II/USA100/ST5 isolate. Screening for
      MRSA colonization on admission does not seem to be productive; however, for
      populations submitted to specific surgeries, active surveillance should be
      implemented.

PMID- 28751037
TI  - Patient-driven hand hygiene audit process at a regional cancer center.
AB  - A patient-driven hand hygiene compliance audit strategy was piloted in a Canadian
      provincial cancer agency during routine provision of cancer outpatient care by
      health care providers (physicians, nurses, and health care aides) under
      conditions where the deployment of an independent external auditor was not
      feasible. The results of the audit suggest the feasibility of this approach as a
      routine institutional performance metric.

PMID- 28751038
TI  - Small hepatocellular carcinomas displayed as a ring enhancing mass on arterial
      phase MRI in the chronically diseased liver.
AB  - AIM: To assess the prevalence of arterial phase (AP) ring-enhancing small
      hepatocellular carcinomas (HCC) on magnetic resonance imaging (MRI); detail
      additional MRI features that enable HCC diagnosis; and examine arterial timing as
      one possible cause of this appearance. MATERIALS AND METHODS: Patients undergoing
      HCC screening with both computed tomography (CT) and MRI within 40 days were
      examined at a single institution over a 7- year time period ending in 2013. From
      this initial group, small (1-3 cm), (AP) ring-enhancing HCC on MRI were studied.
      RESULTS: From the initial group of 64 patients with 129 HCC, 20 patients with 78
      HCCs had a small diameter with 32 (41%) having an AP ring at MRI. The mean age of
      this latter group was 63-years old, with the average tumour diameter of 1.9 cm.
      Histopathology and secondary imaging supported a diagnosis of HCC in 20 (100%)
      patients and 31 (97%) lesions. Most of the ringed lesions had early AP timing.
      CONCLUSION: This study revealed a high prevalence (41%) of small, AP ring HCC
      with MRI. The use of other MRI sequences adds support in making the proper
      diagnosis with this appearance. Early AP timing may help create this pattern.

PMID- 28751039
TI  - Reply.

PMID- 28751040
TI  - Corrigendum to "Serum calcium as an indicator of persistent organ failure in
      acute pancreatitis" [American Journal of Emergency Medicine (2017) 35:978-982].

PMID- 28751041
TI  - Clinical outcomes after Kratom exposures: A poison center case series.

PMID- 28751042
TI  - Spontaneous rupture of the urinary bladder (SRUB): Recovery from cardiopulmonary
      arrest.
AB  - Spontaneous rupture of the urinary bladder (SRUB) is rare and results in a lethal
      condition, i.e., pan peritonitis. However, early and accurate diagnosis of SRUB
      is very difficult. A 54-year-old woman was transported to our hospital with
      suspicion of pan peritonitis after spontaneous return of circulation with
      pulseless electrical activity. Laboratory investigation seemed to indicate acute
      renal failure. Namely, her serum urea and creatinine levels were grossly
      elevated. Exploratory laparotomy showed unexpected rupture of urinary bladder.
      Her recovery after surgery was relatively smooth. SRUB should be considered in
      the differential diagnosis of pan peritonitis, because urgent appropriate
      surgical intervention can rescue patients from this rare lethal disease.

PMID- 28751043
TI  - Atipamezole as an emergency treatment for overdose from highly concentrated alpha
      2 agonists used in zoo and wildlife anesthesia.

PMID- 28751044
TI  - Differently polarized macrophages affect the viability and growth of NSPCs by
      regulating the expression of PACAP.
AB  - : Objective To explore the influence of differently polarized macrophages, M1 or
      M2, to viability and growth of NSPCs and its possible mechanism, especially the
      role of pituitary adenylate cyclase-activating polypeptide (PACAP) in it. METHOD:
      Spinal cord-derived NSPCs were co-cultured with M1 or M2 through a transwell
      system. Growth of NSPCs in both groups was observed through an inverted
      microscope within 3days. NSPCs viability of each group, represented as
      intracellular ATP levels, was measured using the Cellular ATP Kit HTS following
      co-culture for 24h. PACAP levels in the co-cultured NSPCs was alleviated with
      immunofluorescence and Western blot analysis. RESULTS: Morphologically NSPCs
      demonstrated a long spindle shape with short sprout on 3rd day when cultured
      together with M2. NSPCs cultured with M1 showed a small circle or oval shape with
      no obvious sprout. Expression of PACAP was observed in NSPCs co-cultured with M2
      through immunofluorescence. In contrast, NSPCs did not demonstrate PACAP staining
      in the presence of M1 or cultured alone. PACAP in the NSPCs co-cultured with M2
      was upregulated significantly compared with that co-cultured with M1 according to
      Western blot method. The relative ATP level of NSPCs co-cultured with M1 was
      markedly decreased while that with M2 was elevated significantly. That trend
      could be relieved by exogenous PACAP or PACAP 6-38. Viability change of NSPCs by
      M1/M2 correlated with apoptosis. CONCLUSION: Differently polarized macrophages
      could affect the growth and viability of NSPCs by regulating the expression of
      PACAP.

PMID- 28751045
TI  - Corrigendum to Urinary concentrations of organophosphate and carbamate pesticides
      in residents of a vegetarian community [Environment International volume 96
      (2016) 34-40].

PMID- 28751046
TI  - Development of alginate gel beads with a potential use in the treatment against
      acute lead poisoning.
AB  - The objective was to develop alginate beads that could adsorb lead ions in
      gastric pH, in view to preconize their use in gastric lavage following lead
      poisoning. The swelling measurements of both, dry and hydrated beads, were
      carried out in simulated gastric fluid (SGF). The sorption kinetics was examined
      at lead concentrations ranging from 50 to 200mg/l. Calcium released during the
      sorption process was investigated. The swelling rate of the dry beads increased
      considerably with time increase and reached the equilibrium at 736% after 240min;
      concerning the hydrated beads, the equilibrium swelling reached 139% after
      180min. The adsorption of Pb (II) in SGF by dry beads increased with the increase
      of time and initial lead concentration. The adsorption kinetics of Pb ions by
      hydrated alginate beads indicated a rapid binding of Pb ions to the sorbent
      during the first 15min for all the concentrations, followed by a slow increase
      until the equilibrium was reached after 90min. The adsorption capacity of Pb ions
      increased with the increase of the storage time in water at 4 degrees C and with
      the weight. The amount of Ca2+ released by the beads increased with the increase
      of Pb ions a rate.

PMID- 28751047
TI  - Evaluation of anti-inflammatory potential of aqueous extract and polysaccharide
      fraction of Thuja occidentalis Linn. in mice.
AB  - Inflammation is a protective reaction of the microcirculation. However, sustained
      inflammation can lead to undesired effects. Thuja occidentalis Linn has many
      pharmacological properties but has no anti-inflammatory activity described. Thus,
      this study aims evaluating the anti-inflammatory activity of the aqueous extract
      (AE) and the polysaccharide fraction (PLS) of T. occidentalis L. in mice. The
      results of our evaluations in various experimental models indicated that AE and
      PLS (3, 10, and 30mg/kg, i.p.) reduced (p?0.05) paw edema induced by carrageenan,
      dextran sulfate (DEX), compound 48/80, serotonin (5-HT), bradykinin (BK),
      histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, it inhibited
      neutrophils recruitment; decreased MPO activity, tumor necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) levels, vascular permeability, nitrite
      concentration, and MDA concentration; and maintained the GSH levels in the
      peritoneal exudate. The AE and PLS reduced neutrophil infiltration and
      cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) immunostaining
      in paw tissue. Treatment with the AE and PLS (300mg/kg) did not induce gastric
      toxicity. In conclusion, these results show that the AE and PLS reduced the
      inflammatory response by inhibiting vascular and cellular events, inhibiting pro
      inflammatory cytokine production, and reducing oxidative stress. Furthermore,
      they did not induce gastric toxicity at high doses.

PMID- 28751048
TI  - Spectrofluorimetric and molecular docking studies on the interaction of cyanidin
      3-O-glucoside with whey protein, beta-lactoglobulin.
AB  - The interaction of beta-Lactoglobulin (beta-Lg) with cyanidin-3-O-glucoside (C3G)
      was characterized using fluorescence, circular dichroism spectroscopy, and
      docking studies under physiological conditions. Fluorescence studies showed that
      beta-Lg has a strong binding affinity for C3G via hydrophobic interaction with
      the binding constant, Ka, of 3.14*104M-1 at 298K. The secondary structure of beta
      Lg displayed an increase in the major structure of beta-sheet upon binding with
      C3G, whereas a decrease in the minor structure of alpha-helix was also observed.
      In addition, evidenced by near UV-CD, the interaction also disrupted the
      environments of Trp residues. The molecular docking results illustrated that both
      hydrogen bonding and the hydrophobic interaction are involved as an acting force
      during the binding process. These results may contribute to a better
      understanding over the enhanced physicochemical proprieties of anthocyanins due
      to the complexation with milk proteins.

PMID- 28751049
TI  - Cyanobacteria as source of marine bioactive compounds: Molecular specific
      detection based on Delta9 desaturase gene.
AB  - The blue-green microalga, Arthrospira sp., isolated from the sea of Kssour Essef
      in Mahdia (Tunisia), was purified and then identified both morphologically and
      genetically based on 16S rRNA gene sequence. Following physicochemical analysis,
      the prokaryotic microalga tested represented a competitive source of pigments and
      showed a considerable rate in protein (64%) which was confirmed by FTIR
      measurement. The lipid content (4%) was quantified by the gravimetric method and
      the intracellular lipid bodies were detected with the Nile red staining. Using
      gas chromatography coupled with flame ionization detector, the fatty acid profile
      revealed the presence of 27.4% and 32.88% of monounsaturated fatty acids (MUFAs)
      and polyunsaturated fatty acids (PUFAs), respectively. Given the richness of the
      isolated microalga in unsaturated fatty acids, we have developed a SYBR Green
      real time PCR method for the specific identification of Arthrospira sp. Delta9
      desaturase gene. This current method will be of great value for carrying out high
      throughput studies like cloning, heterologous expression and structure-function
      relationship analysis.

PMID- 28751050
TI  - Antimicrobial cerium ion-chitosan crosslinked alginate biopolymer films: A novel
      and potential wound dressing.
AB  - Wound dressings require good antiseptic properties, mechanical strength and, more
      trustably, natural material ingredients. Antimicrobial properties of cerium ions
      and chitosan are known and alginate based wound dressings are commercially
      available. In this study, the advantages of these materials were combined and
      alginate films were crosslinked with cerium(III) solution and chitosan added
      cerium(III) solution. Films were characterized by Fourier transform infrared
      spectroscopy (FTIR), light transmittance, scanning electron microscopy (SEM),
      swelling experiments, water vapor transmittance tests, and mechanical stretching
      tests. The antibacterial and physical properties of the films were compared with
      those of conventional calcium alginate films. Both cerium ion crosslinked and
      cerium ion-chitosan crosslinked alginate films gained antibacterial activity
      against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus
      aureus) bacteria. Cerium alginate-chitosan films showed high resistance to being
      deformed elastically. Results show that cerium alginate-chitosan films can be
      flexible, ultraviolet-protecting, and antibacterial wound dressings.

PMID- 28751051
TI  - New polylactic acid/ cellulose acetate-based antimicrobial interactive single
      dose nanofibrous wound dressing mats.
AB  - New single dose interactive extracellular matrix (ECM) mimicking nanofibrous
      wound dressings based on polylactic acid (PLA) and cellulose acetate (CA) were
      developed, characterized and investigated for wound treatment. The antimicrobial
      agent, thymoquinone (TQ) was selected and incorporated into the scaffolds for
      preventing common clinical infections, and to accelerate the rate of wound
      closure and re-epithelialization. The newly fabricated TQ-loaded PLA/CA wound
      dressings offered many advantages such as mimicking the ECM via the 3D
      nanofibrous structure, and promoted the cell proliferation due to the
      hydrophilicity and bioactivity of CA. The wound dressings also prevented the
      bacterial infection in the early stages due to presence of TQ, and maintained the
      minimum possible bacterial load in the wound area through the sustained release
      of the drug for 9days. In vivo assessment demonstrated that TQ-loaded PLA: CA
      (7:3) scaffolds significantly promoted the wound healing process by increasing re
      epithelialization and controlling the formation of granulation tissue. The
      obtained results suggest that the developed TQ-loaded PLA/CA nanofibrous mats
      could be ideal for wound dressing applications.

PMID- 28751052
TI  - Reduced-molecular-weight derivatives of frost grape polysaccharide.
AB  - A new Type II arabinogalactan was recently described as an abundant gum exudate
      from stems of wild frost grape (Vitus riparia Michx.). The purpose of the current
      study is to more thoroughly characterize the physical properties of this frost
      grape polysaccharide (FGP), and develop methods to modify the molecular weight of
      FGP for potential new applications. Specifically, native FGP was modified by heat
      treatment, digestion with the enzyme L-arabinosidase, and ultrasonication.
      Results showed that native FGP was progressively and irreversibly denatured by
      heat treatment, while the polymer remained largely resistant to enzymatic
      digestion. However, ultrasonication reduced the molecular weight of FGP from
      1.6*107Da to about 3.0*105Da. Reduced-molecular-weight FGP exhibited modified
      solution viscosity properties, which could be useful in food and prebiotic
      applications.

PMID- 28751053
TI  - Validation and Adjustment of the Leipzig-Halifax Acute Aortic Dissection Type A
      Scorecard.
AB  - BACKGROUND: The novel Leipzig-Halifax (LH) scorecard for acute aortic dissection
      type A (AADA) stratifies risk of in-hospital death based on age, malperfusion
      syndromes, critical preoperative state, and coronary disease. The study aim was
      to externally validate the LH scorecard performance and, if adequate, propose
      adjustments. METHODS: All consecutive AADA patients operated on from 1996 to 2016
      (n = 509) were included to generate an external validation cohort. Variables
      related to in-hospital death were analyzed using univariable and multivariable
      analysis. The LH scorecard was applied to the validation cohort, compared with
      the original study, and variable selection was adjusted using validation measures
      for discrimination and calibration. RESULTS: In-hospital mortality rate was 17.7%
      (LH cohort 18.7%). Critical preoperative state and Penn class non-Aa were
      independent predictors (odds ratio [OR] 2.42 and 2.45, respectively) of in
      hospital death. The LH scorecard was adjusted to include Penn class non-Aa,
      critical preoperative state, and coronary disease. Assessing discrimination, area
      under receiver operator characteristic curve for the LH scorecard was 0.61 versus
      0.66 for the new scorecard (p = 0.086). In-hospital mortality rates in low-,
      medium-, and high-risk groups were 14%, 15%, and 48%, respectively (LH scorecard)
      versus 11%, 23%, and 43%, respectively (new scorecard), and goodness-of-fit p
      value was 0.01 versus 0.86, indicating better calibration by the new scorecard. A
      lower Akaike information criterion value, 464 versus 448, favored the new
      scorecard. CONCLUSIONS: Through adjustment of the LH scorecard after external
      validation, prognostic performance improved. Further validated, the LH scorecard
      could be a valuable risk prediction tool.

PMID- 28751055
TI  - Deaths Due to Screenable Cancers Among People Living With HIV Infection, Florida,
      2000-2014.
AB  - INTRODUCTION: Because of antiretroviral therapy, people living with HIV infection
      are surviving longer and are at higher risk for chronic diseases. This study's
      objective was to assess the magnitude of deaths due to cancers for which there
      are screening recommendations for people living with HIV in Florida. METHODS:
      Florida Department of Health Enhanced HIV/AIDS Reporting System data were matched
      with Department of Health Vital Records and the National Death Index to identify
      deaths and their causes through 2014. The sex-specific and cause-specific
      mortality rates and indirect standardized mortality ratios (SMRs, using U.S.
      mortality rates as a standard) were calculated during 2016 for people reported
      with HIV infection 2000-2014. RESULTS: Despite the competing risk of HIV
      mortality, among the 25,678 females, there was a higher risk of cervical
      (SMR=6.32, 95% CI=4.63, 8.44), colorectal (SMR=2.05, 95% CI=1.44, 2.83), liver
      (SMR=8.96, 95% CI=5.39, 14.03), and lung (SMR=5.82, 95% CI=4.80, 6.96) cancer
      mortality and lower risk of breast cancer mortality (SMR=0.57, 95% CI=0.42,
      0.76). Among 63,493 males, there was a higher risk of liver (SMR=5.50, 95%
      CI=4.47, 6.70) and lung (4.63, 95% CI=4.11, 5.19) cancer mortality. Among males,
      the lung cancer SMR significantly declined 2000-2014 (p<0.05), but was still high
      in 2012-2014 (SMR=3.59, 95% CI=2.87, 4.43). CONCLUSIONS: These results indicate
      the importance of primary and secondary cancer prevention during primary care for
      people living with HIV infection.

PMID- 28751054
TI  - The role of bioelectrical impedance analysis, NT-ProBNP and inferior vena cava
      sonography in the assessment of body fluid volume in children with nephrotic
      syndrome.
AB  - BACKGROUND: Assessment of volume status and differentiating "underfill" and
      "overfill" edema is essential in the management of patients with nephrotic
      syndrome (NS). OBJECTIVES: Our aim was to evaluate the volume status of NS
      patients by using different methods and to investigate the utility of
      bioelectrical impedance analysis (BIA) in children with NS. METHODS: The
      hydration status of 19 patients with NS (before treatment of NS and at remission)
      and 25 healthy controls was assessed by multifrequency BIA, serum N-terminal-pro
      brain natriuretic peptide (NT-proBNP) levels, inferior vena cava (IVC) diameter,
      left atrium diameter (LAD) and vasoactive hormones. RESULTS: Renin, aldosterone
      levels, IVC diameter and LAD were not statistically different between the groups.
      NT-proBNP values were statistically higher in the attack period compared to
      remission and the control group (p=0.005 for each). Total body water (TBW),
      overhydration (OH) and extracellular water (ECW) estimated by the BIA measurement
      in the attack group was significantly higher than that of the remission group and
      controls. There were no significant correlations among volume indicators in group
      I and group II. However, significant correlations were observed between NT-proBNP
      and TBW/BSA (p=0.008), ECW/BSA (p=0.003) and ECW/ICW (p=0.023) in the healthy
      group. TBW was found to be higher in patients with NS in association with
      increased ECW but without any change in ICW. NT-proBNP values were higher in
      patients during acute attack than during remission. CONCLUSIONS: Our findings
      support the lack of hypovolaemia in NS during acute attack. In addition, BIA is
      an easy-to-perform method for use in routine clinical practice to determine
      hydration status in patients with NS.

PMID- 28751056
TI  - Federally Qualified Health Center Substitution of Local Health Department
      Services.
AB  - INTRODUCTION: Strategic and budgetary considerations have shifted local health
      departments (LHDs) away from safety net clinical services and toward population
      focused services. Federally Qualified Health Centers (FQHCs) play an increasing
      role in the safety net, and may complement or substitute for LHD clinical
      services. The authors examined the association between FQHC service levels in
      communities and the presence of specific LHD clinical services in 2010 and 2013.
      METHODS: Data from LHD surveys and FQHC service data were merged for 2010 and
      2013. Multivariate regression and instrumental variable methods were used to
      examine FQHC service levels that might predict related LHD service presence or
      discontinuation from 2010 to 2013. RESULTS: There were modest reductions in LHD
      service presence and increases in FQHC service volume over the time period. LHD
      primary care and dental service presence were inversely associated with higher
      related FQHC service volume. LHD prenatal care service presence, as well as a
      measure of change in general service approach, were not significantly associated
      with FQHC service volume. CONCLUSIONS: LHDs were less likely to provide certain
      clinical services where FQHCs provide a greater volume of services, suggesting a
      substitution effect. However, certain clinical services, such as prenatal care,
      may complement the public health mission-and LHDs may be strategically placed to
      continue to deliver these services.

PMID- 28751057
TI  - The role of surgical management in primary small bowel lymphoma: A single-center
      experience.
AB  - INTRODUCTION: Information on primary small intestinal lymphoma is more limited
      than for gastric lymphoma because most of the previous studies did not focus on
      the former. Few prognostic indicators in primary intestinal lymphoma have been
      reliably established because of limited patient numbers and variations in
      criteria for patient selection. In this study, we retrospectively reviewed the
      clinical and pathological characteristics of small intestinal lymphoma cases from
      our hospital, to determine prognostic factors and to clarify the effect of
      surgical resection on prognosis. METHODS: Eighty-two patients were enrolled in
      this retrospective study between January 1997 and December 2012. Patients were
      divided into two groups based on whether or not they underwent surgical
      management. Gross resection was defined as complete removal of the primary
      lesion(s), as confirmed by the naked eye. Combined therapy refers to concurrent
      surgery and chemotherapy. The clinicopathological characteristics and long-term
      outcomes of patients were analyzed and compared between the two groups. RESULTS:
      Most of the patients had abdominal pain (75.6%), and some had loss of body weight
      (29.3%) and bowel perforation (22.0%). Sixty-two patients (75.6%) underwent
      surgical management. Patients in the surgery group presented with fewer B
      symptoms (fever, night sweats, and weight loss; P = 0.035) but more bulky disease
      (P = 0.009). The ileocecal region was the most common site of solitary
      involvement (34.1%). The most common reason for surgery was for tumor-related
      complications (61.3%). Seven patients (11.3%) developed major complications of
      surgery, but these were not related to the indication, timing, or type of
      surgery. Only major surgical complications were statistically significant in
      relation to early mortality (P = 0.004). The estimated 5-year progression-free
      survival (PFS) was 35.1% and 5-year overall survival (OS) was 43.2%. Univariate
      analysis revealed that patients in the surgery group had improved 5-year PFS (P =
      0.028). T-cell lymphoma, involvement of multiple gastrointestinal regions and
      extranodal involvement, higher scores for International Prognostic Index (IPI),
      more advanced Ann Arbor stage, lactate dehydrogenase (LDH) levels above 215 U/L,
      and management without combined therapy were prognostic for shorter PFS and OS in
      univariate analyses. Individuals who received R0 resection or gross resection had
      improved 5-year PFS and OS. Cox regression analysis demonstrated that primary T
      cell lymphoma was an independent negative prognostic factor for both OS and PFS.
      CONCLUSION: Combined therapy is an independent prognostic factor for long-term
      survival in small intestinal lymphoma. Gross resection is recommended in patients
      with small intestinal lymphoma and leads to improved PFS without significantly
      increasing the risk of complications. Emergency surgery does not lead to poor
      prognosis. However, caution is warranted in the management of all patients,
      because of the high risk of post-operative complications and potential for early
      mortality.

PMID- 28751058
TI  - Groin sentinel node biopsy and 18F-FDG PET/CT-supported preoperative lymph node
      assessment in cN0 patients with vulvar cancer currently unfit for minimally
      invasive inguinal surgery: The GroSNaPET study.
AB  - OBJECTIVE: The study aims were: 1) to verify the role of sentinel node biopsy
      (SNB) in a subset of patients with clinical N0 (cN0) invasive vulvar cancer (VC)
      who were still candidates for radical inguinal surgery according to the current
      guidelines; 2) to investigate whether a preoperative 18F-FDG PET/CT (PET/CT)
      evaluation could improve the selection of node negative patients. METHODS: From
      July 2013 to July 2016, all patients with VC admitted to our Division were
      evaluated by standard imaging and clinical exam. Among the patients assessed as
      cN0 we enrolled those unsuitable for SNB, due to: T > 4 cm, multifocal tumors,
      complete tumor diagnostic excision, contralateral nodal involvement and local
      recurrence. A preoperative PET/CT was performed. For each patient surgery
      included SNB, performed using a combined technique (radiotracer plus blue dye),
      followed by standard inguino-femoral lymphadenectomy. The reference standard was
      histopathology. RESULTS: Forty-seven patients entered the study for a total of 73
      groins. Histopathology revealed 12 metastatic SNs in 9 groins. No false negative
      SNs were found (NPV 100%). PET/CT showed a negative predictive value of 93%.
      CONCLUSIONS: Our data suggest that SNB is accurate and safe even in cN0 patients
      currently excluded from this procedure, providing that a careful preoperative
      selection is performed. PET/CT allows a reliable assessment of LN status and may
      be an effective support for the selection of patients who are safe candidates for
      SNB.

PMID- 28751059
TI  - Schmallenberg virus, an emerging viral pathogen of cattle and sheep and a
      potential contaminant of raw materials, is detectable by classical in-vitro
      adventitious virus assays.
AB  - Emerging viruses, as potential contaminants of raw materials used in the
      manufacture of biologicals represent a challenge in the safety testing of
      biopharmaceutical products intended for human or veterinary use. Here, we report
      the challenge of an in vitro adventitious virus platform used in safety testing
      of biologicals, where a broad panel of detector cell lines was challenged to
      provide evidence that Schmallenberg virus is detectable by a classical reporting
      endpoint of cytopathic effect with Vero, BHK-21 and CHO-K1 detector cells, within
      typical in vitro assay timescales. We conclude that Schmallenberg virus is
      robustly detectable by classical in vitro viral biosafety assays.

PMID- 28751060
TI  - Should classification as an ACS-NSQIP high outlier be used to direct hospital
      quality improvement efforts?
AB  - BACKGROUND: ACS-NSQIP classifies hospitals as "high outliers" if their
      performance is significantly worse than expected. We determined how often
      hospitals return to as-expected performance after being newly identified as
      outliers. METHODS: Outlier status was identified in ACS-NSQIP semi-annual reports
      (SARs) 2008-2011 for 13 postoperative adverse events. Pearson correlation and R2
      measured the relationship between frequency of changes in outlier status,
      frequency of outlier identification, and adverse event rate. RESULTS: Among 284
      hospitals, 75% were classified as high outliers for an adverse event at least
      once. New high outliers frequently did not remain outliers in the next SAR. Of
      new outliers, mortality had the highest percentage return to as-expected
      performance (62.7%), while surgical site infection had the lowest (20.5%). The
      likelihood of an outlier hospital returning to as-expected performance was
      inversely related to the percentage of hospitals classified as outliers. The
      percentage of hospitals classified as outliers for an event explained 60% of
      variation in outlier hospitals returning to as-expected performance. CONCLUSIONS:
      Outlier status may be less meaningful for adverse events with relatively few
      outlier hospitals.

PMID- 28751061
TI  - Parental leave policies in graduate medical education: A systematic review.
AB  - BACKGROUND: A thorough understanding of attitudes toward and program policies for
      parenthood in graduate medical education (GME) is essential for establishing fair
      and achievable parental leave policies and fostering a culture of support for
      trainees during GME. METHODS: A systematic review of the literature was
      completed. Non-cohort studies, studies completed or published outside of the
      United States, and studies not published in English were excluded. Studies that
      addressed the existence of parental leave policies in GME were identified and
      were the focus of this study. RESULTS: Twenty-eight studies addressed the topic
      of the existence of formal parental leave policies in GME, which was found to
      vary across time and ranged between 22 and 90%. Support for such policies
      persisted across time. CONCLUSIONS: Attention to formal leave policies in GME has
      traditionally been lacking, but may be increasing. Negative attitudes towards
      parenthood in GME persist. Active awareness of the challenges faced by parent
      trainees combined with formal parental leave policy implementation is important
      in supporting parenthood in GME.

PMID- 28751062
TI  - Model for prioritization of Graduate Medical Education funding at a university
      setting - Engagement of GME committee with the Clinical Enterprise.
AB  - BACKGROUND: Funding for graduate medical education (GME) is becoming scarce and
      is likely to worsen. There is a higher degree of accountability and return on
      investment demanded from public funds dedicated to GME. Academic centers (AC)
      partnered with clinical enterprises (CE) are finding it increasingly difficult to
      retain sustainable funding streams for GME activities. METHODS: To develop and
      implement a novel algorithmic funding model at one AC in symbiotic partnership
      with the CE for all 50 GME programs with nearly 500 residents. RESULTS: A new GME
      Finance and Workforce Committee was convened which was tasked with developing the
      novel algorithmic financial model to prioritize GME funding. Early outcomes
      measures that were monitored consisted of: satisfaction of all stakeholders and
      financial savings. CONCLUSIONS: The model was presented to all the stakeholders
      and was well received and approved. Early signs, demonstrated AC and CE
      satisfaction with the model, financial savings and increased efficiency. This GME
      funding model may serve as a template for other academic centers with tailored
      modifications to suit their local needs, demands and constraints.

PMID- 28751063
TI  - A prospective randomized study comparing laparoscopic transabdominal
      preperitoneal (TAPP) versus Lichtenstein repair for bilateral inguinal hernias.
AB  - BACKGROUND: In literature, only a few studies have prospectively compared the
      results of laparoscopic with open inguinal hernia repair yet none have compared
      bilateral inguinal hernia repair. The aim of this study is to compare the open
      Lichtenstein repair (OLR) with laparoscopic trans-abdominal preperitoneal (TAPP)
      repair in patients undergoing surgery for bilateral inguinal hernia. METHODS:
      Patients were prospectively randomized between March 2013 and March 2015. Outcome
      parameters included hospital stay, operation time, postoperative complications,
      immediate postoperative pain and chronic pain, recurrence and quality of life.
      RESULTS: Sixty-one patients underwent TAPP repair and 73 underwent OLR. TAPP
      procedure had less early post-operative pain up to 7 days from surgery (p =
      0.003), a shorter length of hospital stay (p = 0.001), less postoperative
      complications (p = 0.012) and less chronic pain (0.04) when compared with the OLR
      approach. CONCLUSIONS: TAPP procedure for bilateral inguinal hernia effectively
      reduces early postoperative pain, hospital stay and postoperative complications.

PMID- 28751064
TI  - Structure, interfacial film properties, and thermal fluctuations of
      microemulsions as seen by scattering experiments.
AB  - The physics of microemulsions and in particular Dominique Langevin's
      contributions to the understanding of microemulsion structure and bending
      properties using scattering techniques are reviewed. Among the many methods used
      by her and her co-workers, we particularly emphasize optical techniques and small
      angle neutron scattering (SANS), but also neutron spin echo spectroscopy (NSE).
      The review is then extended to more recent studies of properties of
      microemulsions close to surfaces, using reflectometry and grazing-incidence small
      angle neutron scattering (GISANS).

PMID- 28751065
TI  - [Care pathway of patients with hepatocellular carcinoma in France: State of play
      in 2017].
AB  - Hepatocellular carcinoma is a major public health problem with one of the highest
      overall mortality compared to other cancers. The median overall survival in
      France in a hospital population with hepatocellular carcinoma is 9.4 months.
      Several publications reported a positive impact of hepatocellular carcinoma
      screening on diagnosis at an early-stage, eligibility for curative treatment and
      overall survival. However, the identification of patients to be included in a
      hepatocellular carcinoma screening program and the application of screening
      recommendations are not optimal. Other studies suggest a potentially negative
      impact of delayed diagnosis or treatment initiation on the patient's prognosis.
      Finally, marked variations between French regions and departments have been
      described in terms of access to curative treatment and overall survival. In this
      review article, we propose a state of play of the hepatocellular carcinoma
      patient's care pathway in France with the aim of identifying potential breaking
      points with negative impact on prognosis and of developing proposals for
      improvement.

PMID- 28751066
TI  - [Crohn's disease and hidradenitis suppurativa: An announced crisis?]

PMID- 28751067
TI  - When love makes a lover (transiently) blind: A case report describing postcoital
      Valsalva retinopathy.

PMID- 28751068
TI  - DOPA Decarboxylase Modulates Tau Toxicity.
AB  - BACKGROUND: The microtubule-associated protein tau accumulates into toxic
      aggregates in multiple neurodegenerative diseases. We found previously that loss
      of D2-family dopamine receptors ameliorated tauopathy in multiple models
      including a Caenorhabditis elegans model of tauopathy. METHODS: To better
      understand how loss of D2-family dopamine receptors can ameliorate tau toxicity,
      we screened a collection of C. elegans mutations in dopamine-related genes (n =
      45) for changes in tau transgene-induced behavioral defects. These included many
      genes responsible for dopamine synthesis, metabolism, and signaling downstream of
      the D2 receptors. RESULTS: We identified one dopamine synthesis gene, DOPA
      decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms.
      Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of
      tau transgenic worms, reduced phosphorylated and detergent-insoluble tau
      accumulation, and reduced tau-mediated neuron loss. Loss of function in other
      genes in the dopamine and serotonin synthesis pathways did not alter tau-induced
      toxicity; however, their function is required for the suppression of tau toxicity
      by bas-1. Additional loss of D2-family dopamine receptors did not synergize with
      bas-1 suppression of tauopathy phenotypes. CONCLUSIONS: Loss of the DDC bas-1
      reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no
      other dopamine or serotonin synthesis genes tested had this effect. Because loss
      of activity upstream of DDC could reduce suppression of tau by DDC, this suggests
      the possibility that loss of DDC suppresses tau via the combined accumulation of
      dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan.

PMID- 28751069
TI  - Activity-Dependent Brain-Derived Neurotrophic Factor Release Is Required for the
      Rapid Antidepressant Actions of Scopolamine.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a key role in the
      pathophysiology and treatment of depression. Recent clinical studies demonstrate
      that scopolamine, a nonselective muscarinic acetylcholine receptor antagonist,
      produces rapid antidepressant effects in patients with depression. Rodent studies
      demonstrate that scopolamine increases glutamate transmission and synaptogenesis
      in the medial prefrontal cortex (mPFC). Here we tested the hypothesis that
      activity-dependent BDNF release within the mPFC is necessary for the
      antidepressant actions of scopolamine. METHODS: Behavioral effects of scopolamine
      were assessed in BDNF Val/Met knock-in mice, in which BDNF processing and release
      are impaired. In addition, intra-mPFC infusion of a BDNF-neutralizing antibody
      was performed to test the necessity of BDNF release in driving scopolamine
      induced behavioral responses. Further in vivo and in vitro experiments were
      performed to delineate BDNF-dependent mechanisms underlying the effects of
      scopolamine. RESULTS: We found that BDNF Met/Met mice have attenuated responses
      to scopolamine and that anti-BDNF antibody infusions into the mPFC prevented the
      antidepressant-like behavioral effects of scopolamine. In vitro experiments show
      that scopolamine rapidly stimulates BDNF release and tropomyosin receptor kinase
      B-extracellular signal-regulated kinase signaling. Moreover, these effects
      require alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor
      activation and are blocked by neuronal silencing. Importantly, pretreatment with
      verapamil prevented scopolamine-induced behavioral responses and BDNF-tropomyosin
      receptor kinase B signaling, suggesting that these effects are dependent on
      activation of voltage-dependent calcium channels. CONCLUSIONS: The results
      identify an essential role for activity-dependent BDNF release in the rapid
      antidepressant effects of scopolamine. Attenuation of responses in BDNF Met mice
      indicates that patients with the Met allele may be less responsive to
      scopolamine.

PMID- 28751070
TI  - The urgent need to improve the tools to assess clinical benefit and value of
      cancer treatment.
AB  - There are several controversies in the assessment of the benefit, value and
      sustainability of cancer drugs. First, there is a surprising disagreement on the
      impact of drugs on the overall outcome of cancer treatment. Second, raising the
      bar of efficacy in clinical trials is claimed by many, but at the same time,
      being conservative appears justified as well, given the overall benefit of
      multiple incremental gains, typically observed in advanced solid tumours. Third,
      sustainability of cancer drug cost is a prohibitive challenge, but no major
      successful action has been taken so far. The reason for these controversies can
      be understood using concepts borrowed from psychological and cognitive sciences:
      each stakeholder has different perspectives generated by different availability
      biases; this implies different priorities, leading people to think, choose and
      act differently. Providing an 'objective' assessment of the benefit and value of
      a cancer drug makes sense only if the perspective adopted is clearly identified.
      The American Society of Clinical Oncology (ASCO) scale fits the patients'
      perspective by helping individual patients to choose the most valuable
      therapeutic option for their condition. Conversely, the European Society for
      Medical Oncology (ESMO) scale has a public health perspective: ranking the
      clinical benefit of oncologic drugs to identify those agents that should be
      available in every EU country. Because this scale is being adopted for
      reimbursement purposes in several European regions, the current major
      methodological problems of the scale should urgently be corrected to avoid
      unwanted societal consequences.

PMID- 28751071
TI  - Response to: Neoadjuvant chemoradiotherapy for oesophageal cancer: Still looking
      for a challenger to the CROSS regimen.

PMID- 28751072
TI  - The interrelationship of microstructure and hardness of human coronal dentin
      using reference point indentation technique and micro-Raman spectroscopy.
AB  - OBJECTIVES: The aim of this paper is to determine the interrelationship between
      the microstructure - in terms of chemical composition and crystallinity - to the
      microhardness of coronal dentin. METHODS: Dentin microhardness was tested by a
      novel reference point indenter and compared to the traditional Knoop hardness
      method. Micro-Raman spectroscopy was used to determine the chemical composition
      and crystallinity of dentin. RESULTS: From the occlusal groove to the border of
      the coronal pulp chamber, dentin hardness decreased from superficial dentin (SD)
      to deep dentin (DD). Mineral/organic matrix ratios (phosphate/CH and
      phosphate/amide I) also decreased from SD to DD; however, this change was
      significant (P<0.05) in the phosphate/amide I ratio only. The phosphate/carbonate
      ratio decreased significantly by varying position from SD to DD. The degree of
      the crystallinity, as measured by the full width at half maximum (FWHM) of the
      peak at 960cm-1, decreased significantly going from superficial to deep dentin.
      SIGNIFICANCE: For the first time, the interrelationship between the
      microstructure and the mechanical properties of coronal dentin was determined by
      using the novel reference point indentation technique and micro-Raman
      spectroscopy. We hypothesize that the decrease in hardness from superficial to
      deep dentin can potentially be explained by decreased mineral content and
      increased carbonate content, which is also associated with decreased
      crystallinity. Collectively, there is a positive association between dentin
      hardness and mineral content and a negative association between dentin hardness
      and carbonate content.

PMID- 28751073
TI  - Efficacy of new natural biomodification agents from Anacardiaceae extracts on
      dentin collagen cross-linking.
AB  - OBJECTIVES: Several polyphenols from renewable sources were surveyed for dentin
      biomodification. However, phenols from cashew nut shell liquid (CNSL, Anacardium
      occidentale) and from Aroeira (Myracrodruon urundeuva) extract have never been
      evaluated. The present investigation aimed to compare the dentin collagen
      crosslinking (biomodification) effectiveness of polyphenols from Aroeira stem
      bark extract, proanthocyanidins (PACs) from grape-seed extract (Vitis vinifera),
      cardol and cardanol from CNSL after clinically relevant treatment for one minute.
      METHODS: Three-point bending test was used to obtain the elastic modulus of fully
      demineralized dentin beams before and after biomodification, whilst color change
      and mass variation were evaluated after four weeks water biodegradation. Color
      aspect was assessed by optical images after biodegradation whereas collagen cross
      linking was investigated by micro-Raman spectroscopy. Statistical analysis was
      performed with repeated-measures two way ANOVA and Tukey's test (p<0.05).
      RESULTS: The increase in elastic modulus after biomodification was in the order
      cardol>cardanol>aroeira=PACs with cardol solution achieving mean 338.2% increase.
      The mass increase after biomodification followed the same order aforementioned.
      Nevertheless, after four weeks aging, more hydrophobic agent (cardanol) induced
      the highest resistance against water biodegradation. Aroeira and cardol attained
      intermediate outcomes whereas PACs provided the lower resistance. Tannin-based
      agents (Aroeira and PACs) stained the specimens in dark brown color. No color
      alteration was observed with cardol and cardanol treatments. All four agents
      achieved crosslinking in micro-Raman after one minute application. SIGNIFICANCE:
      In conclusion, major components of CNSL yield overall best dentin biomodification
      outcomes when applied for one minute without staining the dentin collagen.

PMID- 28751074
TI  - Corrigendum to "Functional expression of a putative geraniol 8-hydroxylase by
      reconstitution of bacterially expressed plant CYP76F45 and NADPH-cytochrome P450
      reductase CPR I from Croton stellatopilosus Ohba" [Phytochemistry 118 (2015) 204
      215].

PMID- 28751075
TI  - Effects of physical activity and breaks on mathematics engagement in adolescents.
AB  - OBJECTIVES: The purpose of this study was to determine whether physical activity
      has a positive relationship with school engagement regardless of the presence or
      absence of a recess or lunch break before the classroom lesson. DESIGN: Data were
      collected over three ten-week periods: January-April 2014 (Time 1), October
      December 2014 (Time 2), and April-June 2015 (Time 3). METHODS: A cohort of 2194
      adolescents (mean age=13.40years, SD=.73) wore an accelerometer during the hour
      before a mathematics lesson and completed a questionnaire following the
      mathematics lesson to assess school engagement in that lesson. RESULTS: Linear
      mixed models indicated that moderate-intensity activity before a mathematics
      lesson had a positive linear relationship with cognitive engagement (beta=.40,
      p<.05). Recess breaks before a mathematics lesson had a negative relationship
      with overall, behavioural, emotional, and cognitive engagement (beta=-.18, p<.01,
      beta=-.19, p<.01, beta=-.13, p=.03, and beta=-.13, p=.04, respectively).
      CONCLUSIONS: Promoting moderate-intensity activity prior to mathematics lessons
      could improve students' cognitive engagement. Educators should be aware that
      students tend to demonstrate the lowest levels of school engagement after recess
      breaks.

PMID- 28751076
TI  - Periodontal tactile sensation and occlusal loading condition of autotransplanted
      teeth: A retrospective pilot study.
AB  - PURPOSE: The objectives of this retrospective pilot study were: (1) to examine
      the occlusal properties (periodontal tactile sensation, occlusal force support
      ability, dynamic tooth mobility, occlusal force, contact area, preferred chewing
      side and main occluding area) of autotransplanted teeth with no clinical
      complications after transplantation (postoperative periods from 1 to 7 years).
      METHODS: Three groups were formed from 20 subjects (23 teeth in each group):
      autotransplanted teeth (ATP group), teeth contralateral to the recipient site
      (control group A), and teeth contralateral to the donor site (control group B).
      RESULTS: The tactile detection threshold of the ATP group was higher than both
      the control groups, and the individual occlusal force was significantly lower
      than control group A. The occlusal force ratio and the occlusal contact area
      ratio were significantly lower in the ATP group than in both control groups,
      while the mobility was similar in all groups. Eight out of 20 subjects chose the
      autotransplanted teeth side as the preferred chewing side. Especially when the
      recipient site was the first molar, the ATP of these subjects were included in
      the main occluding area. The pocket depth of the three groups was within the
      normal range. CONCLUSIONS: These results demonstrate that teeth
      autotransplantation can achieve a mastication efficiency and periodontal
      condition similar to normal teeth; however, without proper healing, the
      periodontal sensation of autotransplanted teeth may be inferior to that of normal
      teeth (<250).

PMID- 28751077
TI  - Validation of the French Version of the Edmonton Symptom Assessment System.
AB  - CONTEXT: The Edmonton Symptom Assessment System (ESAS) is a brief, widely
      adopted, multidimensional questionnaire to evaluate patient-reported symptoms.
      OBJECTIVES: The objective of this study was to define a standard French version
      of the ESAS (F-ESAS) to determine the psychometric properties in French-speaking
      patients. METHODS: In a first pilot study, health professionals (n = 20) and
      patients (n = 33) defined the most adapted terms in French (F-ESAS). In a
      prospective multicentric study, palliative care patients completed the three
      forms of F-ESAS (F-ESAS-VI, F-ESAS-VE, and F-ESAS-NU, where VI is visual, VE,
      verbal, and NU, numerical), the Hospital Anxiety and Depression Scale. All
      patients had a test-retest evaluation during the same half-day. Standardized
      distraction material was used between each scale. RESULTS: One hundred twenty
      four patients were included (mean age [+/-SD]: 68.3 +/- 12; 70 women; 54 men).
      Test-retest reliability was high for all three F-ESAS, and the correlation
      between these scales was nearly perfect (Spearman rs = 0.66-0.91; P < 0.05). F
      ESAS-VI, F-ESAS-VE, and F-ESAS-NU performed similarly and were equally reliable,
      although there was a trend toward lower reliability for F-ESAS-VI. Correlation
      between F-ESAS depression and anxiety and HADS depression and anxiety,
      respectively, were positive (Spearman rs = 0.38-0.41 for depression; Spearman rs
      = 0.48-0.57 for anxiety, P < 0.05). Among patients, 59 (48%), 45 (36%), and 20
      (16%) preferred to assess their symptoms with F-ESAS-VE, F-ESAS-NU, and F-ESAS
      VI, respectively. CONCLUSION: The F-ESAS is a valid and reliable tool for
      measuring multidimensional symptoms in French-speaking patients with an advanced
      cancer. All forms of F-ESAS performed well with a trend for better psychometric
      performance for F-ESAS-NU, but patients preferred the F-ESAS-VE.

PMID- 28751078
TI  - The Quality Improvement Environment: Results of the 2016 AAHPM/HPNA Membership
      Needs Assessment Survey.
AB  - CONTEXT: The American Academy of Hospice and Palliative Medicine (AAHPM) and
      Hospice and Palliative Nurses Association (HPNA) convened the Measuring What
      Matters (MWM) initiative in 2013, which recommended 10 quality performance
      measures; yet, little is known about the quality improvement (QI) environment and
      implementation of the MWM among hospices and palliative care services.
      OBJECTIVES: The objective of this study was to describe the findings of the 2016
      AAHPM/HPNA Needs Assessment survey exploring the QI environment among hospice and
      palliative care services. METHODS: An online survey was distributed to
      approximately 16,500 AAHPM and HPNA members, and other hospice and palliative
      care organizations were invited to respond. Summary data and individual write-in
      responses were collated and analyzed. Data analysis included generating
      descriptive statistics and analyzing individual write-in responses for additional
      information and themes. RESULTS: More than 1000 responses were received. Most
      organizations had a designated QI leader and used an electronic medical record.
      Less than 50% of systems had fields for palliative care information. The top
      three MWM measures collected through an electronic medical record were pain
      treatment (66%), screening for physical symptoms (55%), and comprehensive
      assessment (54%). The most common barrier to implementing QI was time constraint.
      Most respondents had received no training and education in how to implement QI.
      CONCLUSIONS: The 2016 AAHPM/HPNA Needs Assessment Survey provided important
      information about the QI systems and measurement environment within hospice and
      palliative care services. Survey insights can aid AAHPM/HPNA in developing
      resources to empower hospice and palliative care clinicians to make QIs that
      matter for their patients and families.

PMID- 28751079
TI  - One Size Does Not Fit All: Disease Profiles of Serious Illness Patients Receiving
      Specialty Palliative Care.
AB  - INTRODUCTION: Understanding the symptom profiles of seriously ill patients who
      receive palliative care, especially noncancer diagnoses where the data are sparse
      and are critical to better targeting our resources to the needs of patients.
      METHODS: We performed a retrospective, multicohort study of patients evaluated
      during their first consultative palliative care visit in a community-based
      palliative care registry. We placed into one of seven major disease categories
      based on clinician-reported primary diagnosis for consultation. Our primary aim
      of this analysis was to determine the univariate association between several
      patient-specific characteristics (e.g., demographics, care of setting, initial
      screening score) and the primary diagnosis. RESULTS: We evaluated the first visit
      consultation records of 1615 patients. Most prevalent diagnosis was Neurologic
      (564; 35%), followed by Cardiovascular (266; 16%), Pulmonary (229; 14%), and
      Cancer (208; 13%). Patients in the study with the highest symptom burden were
      those diagnosed with cancer or pulmonary disease, with 45% and 37% of cancer and
      pulmonary patients, respectively, having two or more moderate-to-severe symptoms;
      26% of cardiovascular disease patients reported two or more moderate-to-severe
      symptoms, whereas 11% reported three or more. Patients with a neurologic or
      infectious diagnosis had less symptom burden, but a large percentage of
      neurologic patients were unable to respond. DISCUSSION: This study is one of the
      first to describe symptom burden and functional scores by diagnostic categories
      and care settings across a community-based interdisciplinary specialty palliative
      care program. Results demonstrated statistically significant and clinically
      relevant differences among settings of care, functional status, and symptom
      profiles between patients with various serious illnesses.

PMID- 28751080
TI  - Non-alcoholic fatty liver disease: A poorly known pandemic.
AB  - Non-alcoholic fatty liver disease (NAFLD) consists of an excessive depositing of
      fat in the liver, which can end up by causing inflammation, fibrosis and also
      cirrhosis with the corresponding complications including liver cancer. NAFLD has
      become the most common liver disease worldwide. The incidence has increased in
      parallel with the obesity, diabetes and metabolic syndrome epidemic, thus
      resulting in becoming one of the main indications for liver transplant. The
      diagnosis has principally been through histology but with the development of non
      invasive methods, these have helped in simplifying the management of these
      patients in clinical practice. The only therapeutic strategies currently
      available are focused on weight loss (lifestyle changes or bariatric surgery).
      There is still no approved pharmacological option for the treatment of NAFLD,
      however there are a number of molecular studies in advanced stages of
      development.

PMID- 28751081
TI  - Mammography screening, what does the future hold?

PMID- 28751082
TI  - Acute pancreatitis caused by Campylobacter jejuni in a child with cystic
      fibrosis.

PMID- 28751083
TI  - Proposed action for detection and care of victims of hate violence for health
      professionals.

PMID- 28751084
TI  - Late diagnosis of 1b pseudohypoparathyroidism.

PMID- 28751085
TI  - Risks associated with the direct introduction of solid food in infants.

PMID- 28751086
TI  - High Risk, Low Frequency: Optimizing Performance of Emergency Intubation for
      Children.

PMID- 28751087
TI  - The Effect of Medicaid Expansion on Utilization in Maryland Emergency
      Departments.
AB  - STUDY OBJECTIVE: A proposed benefit of expanding Medicaid eligibility under the
      Patient Protection and Affordable Care Act (ACA) was a reduction in emergency
      department (ED) utilization for primary care needs. Pre-ACA studies found that
      new Medicaid enrollees increased their ED utilization rates, but the effect on
      system-level ED visits was less clear. Our objective was to estimate the effect
      of Medicaid expansion on aggregate and individual-based ED utilization patterns
      within Maryland. METHODS: We performed a retrospective cross-sectional study of
      ED utilization patterns across Maryland, using data from Maryland's Health
      Services Cost Review Commission. We also analyzed utilization differences between
      pre-ACA (July 2012 to December 2013) uninsured patients who returned post-ACA
      (July 2014 to December 2015). RESULTS: The total number of ED visits in Maryland
      decreased by 36,531 (-1.2%) between the 6 quarters pre-ACA and the 6 quarters
      post-ACA. Medicaid-covered ED visits increased from 23.3% to 28.9% (159,004
      additional visits), whereas uninsured patient visits decreased from 16.3% to
      10.4% (181,607 fewer visits). Coverage by other insurance types remained largely
      stable between periods. We found no significant relationship between Medicaid
      expansion and changes in ED volume by hospital. For patients uninsured pre-ACA
      who returned post-ACA, the adjusted visits per person during 6 quarters was 2.38
      (95% confidence interval 2.35 to 2.40) for those newly enrolled in Medicaid post
      ACA compared with 1.66 (95% confidence interval 1.64 to 1.68) for those remaining
      uninsured. CONCLUSION: There was a substantial increase in patients covered by
      Medicaid in the post-ACA period, but this did not significantly affect total ED
      volume. Returning patients newly enrolled in Medicaid visited the ED more than
      their uninsured counterparts; however, this cohort accounted for only a small
      percentage of total ED visits in Maryland.

PMID- 28751088
TI  - Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer
      bleeding under proton pump inhibitor use.
AB  - BACKGROUND/PURPOSE: Peptic ulcer bleeding remains a deadly disease, and a simple
      indicator of long-term outcomes is crucial. This study validated whether
      hypoalbuminemia and its related factors in patients with peptic ulcer bleeding
      can indicate long-term mortality and rebleeding under proton pump inhibitor use.
      METHODS: The prospective cohort study enrolled 426 patients with peptic ulcer
      bleeding who had high risk stigmata at endoscopy and had received endoscopic
      hemostasis. They were divided into 79 patients in the hypoalbuminemia group (Hypo
      AG, serum albumin <28 g/L), 135 in the marginal hypoalbuminemia group (Margin-AG,
      serum albumin 28-34.9 g/L), and 212 in the normal albuminemia group (Normal-AG,
      serum albumin >=35 g/L). Each subject received 72-h of intravenous infusion and
      then the oral form of proton pump inhibitors and were monitored for 84 days to
      assess all-cause mortality and recurrent bleeding. RESULTS: The primary outcome
      of all-cause mortality rates were increased in a stepwise fashion in a trend from
      Normal-AG, Margin-AG, to Hypo-AG (0-28th day: 1.9%, 2.2%, 12.8%, p < 0.001; 29th
      84th day: 2.5%, 8.0%, 10.6%, p < 0.01). The secondary outcome of recurrent
      bleeding rates were also increased in the same fashion (0-28th day: 6.4%, 15.4%,
      24.6%, p < 0.001; 29th-84th day: 0%, 3.0%, 4.2%, p = 0.01). Abnormal albuminemia
      was <30 g/L related to hemoglobin levels <70 g/L, nosocomial bleeding, cirrhosis,
      age >=70 years, shock, and ulcer size >=1.0 cm independently (p < 0.05).
      CONCLUSION: Hypoalbuminemia in patients with peptic ulcer bleeding can be an
      alarm indicator of all-cause mortality and recurrent bleeding in a long-term
      follow-up situation under proton pump inhibitor use (NCT01591083).

PMID- 28751089
TI  - Significant association of high-grade inflammation and thick lining epithelium
      with the increased number of Langerhans cells in dentigerous cysts.
AB  - BACKGROUND/PURPOSE: Langerhans cells (LCs) are antigen-presenting cells. This
      study assessed the LC counts in 80 dentigerous cysts (DCs). METHODS: The CD1a
      positive LC numbers in the lining epithelia and subepithelial connective tissues
      were counted at 80 DC sites without inflammation, 33 DC sites with mild/moderate
      inflammation, and 9 DC sites with severe inflammation from 80 DC specimens.
      RESULTS: The mean LC counts in the lining epithelia and subepithelial connective
      tissues increased significantly from no inflammation (0.5 +/- 0.5 and 0.2 +/- 0.3
      cell/high-power field or HPF, respectively) through mild/moderate inflammation
      (6.8 +/- 1.8 and 2.4 +/- 2.0 cells/HPF, respectively) to severe inflammation DC
      sites (18.9 +/- 7.0 and 6.7 +/- 5.8 cells/HPF, respectively; all P-values <
      0.001). DC sites with inflammation had thicker lining epithelia than those
      without inflammation. Moreover, the mean LC counts in the lining epithelia and
      subepithelial connective tissues of DCs were significantly higher in the thicker
      lining epithelium (>50 MUm) group (7.4 +/- 6.5 and 2.6 +/- 3.4 cells/HPF,
      respectively) than in the thinner lining epithelium (? 50 MUm) group (0.5 +/- 0.5
      and 0.2 +/- 0.3 cells/HPF, respectively; both P-values < 0.001). CONCLUSION: A
      significant association of high-grade inflammation and thick lining epithelium
      with the increased LC number in DCs is found. The finding of few LCs in the
      lining epithelia of DCs without inflammation indicates the reduced
      immunosurveillance ability against DC lining epithelial cells in DC patients. It
      needs further studies to confirm the role of reduced immunosurveillance in the
      enlargement of the DC.

PMID- 28751090
TI  - The effectiveness of styrene-maleic acid (SMA) copolymers for solubilisation of
      integral membrane proteins from SMA-accessible and SMA-resistant membranes.
AB  - Solubilisation of biological lipid bilayer membranes for analysis of their
      protein complement has traditionally been carried out using detergents, but there
      is increasing interest in the use of amphiphilic copolymers such as styrene
      maleic acid (SMA) for the solubilisation, purification and characterisation of
      integral membrane proteins in the form of protein/lipid nanodiscs. Here we survey
      the effectiveness of various commercially-available formulations of the SMA
      copolymer in solubilising Rhodobacter sphaeroides reaction centres (RCs) from
      photosynthetic membranes. We find that formulations of SMA with a 2:1 or 3:1
      ratio of styrene to maleic acid are almost as effective as detergent in
      solubilising RCs, with the best solubilisation by short chain variants (<30kDa
      weight average molecular weight). The effectiveness of 10kDa 2:1 and 3:1
      formulations of SMA to solubilise RCs gradually declined when genetically-encoded
      coiled-coil bundles were used to artificially tether normally monomeric RCs into
      dimeric, trimeric and tetrameric multimers. The ability of SMA to solubilise
      reaction centre-light harvesting 1 (RC-LH1) complexes from densely packed and
      highly ordered photosynthetic membranes was uniformly low, but could be increased
      through a variety of treatments to increase the lipid:protein ratio. However,
      proteins isolated from such membranes comprised clusters of complexes in small
      membrane patches rather than individual proteins. We conclude that short-chain
      2:1 and 3:1 formulations of SMA are the most effective in solubilising integral
      membrane proteins, but that solubilisation efficiencies are strongly influenced
      by the size of the target protein and the density of packing of proteins in the
      membrane.

PMID- 28751091
TI  - Ultraslow dynamics of a complex amphiphile within the phospholipid bilayer:
      Effect of the lipid pre-transition.
AB  - The shape and intensity of fluorescence emission spectra of Merocyanine 540
      embedded in dipalmitoylphosphatidylcholine bilayers differ depending on the
      thermal history of the sample. This apparent hysteresis in fluorescence emission
      was most prominent in the temperature range of 20 to 35 degrees C. Analysis of
      kinetic and temperature cycling experiments suggested that Merocyanine 540 slowly
      (half time of about 30min) assumes a metastable configuration as temperature is
      raised above the phospholipid pre-transition point. When the sample was cooled
      below the pre-transition temperature, the metastable state slowly depopulated
      (half time of about 15min). The rate of merocyanine exchange among these states
      was influenced more by membrane lipid mobility than by lipid order since
      cholesterol increased the rate of transition to the metastable state by a factor
      of 11.

PMID- 28751092
TI  - The incidence and effect of fatty atrophy, positive tangent sign, and rotator
      cuff tears on outcomes after total shoulder arthroplasty.
AB  - BACKGROUND: Treatment choices for total shoulder arthroplasty (TSA) in the
      absence of full-thickness rotator cuff tears (RCTs) are not clearly defined in
      current literature. This study investigated the prevalence and effect of
      preoperative partial-thickness RCTs and muscular degenerative changes on
      postoperative outcomes after TSA. METHODS: Medical records and magnetic resonance
      imaging studies were reviewed for patients who underwent TSA for primary
      glenohumeral osteoarthritis with minimum 2-year follow-up to determine
      preoperative tear classification, Goutallier grade, and supraspinatus tangent
      sign. Postoperative pain on the visual analog scale, range of motion, and patient
      outcomes scores were obtained to correlate preoperative RCT status, Goutallier
      grading, tangent sign, and postoperative outcomes. Patients with full-thickness
      RCT on preoperative magnetic resonance imaging were excluded. RESULTS: Forty-five
      patients met all inclusion criteria (average age, 65 +/- 10 years; average follow
      up, 43 months). Of the patients undergoing TSA, 40% had a significant (>50%
      thickness) partial RCT. Grade 3 to 4 Goutallier changes were noted in 22% of all
      patients, and 13% demonstrated grade 3 to 4 changes in the context of no tear.
      Positive tangent sign was present in 7% of all patients. The preoperative
      Goutallier grade of the infraspinatus was significantly negatively correlated
      with postoperative forward elevation (P = .02) and external rotation (P = .05),
      but rotator cuff pathology, including tear status, Goutallier grade, and the
      presence of a tangent sign, did not correlate with postoperative functional
      outcome scores. CONCLUSIONS: Even in the absence of a full-thickness RCT, rotator
      cuff atrophy, fatty infiltration, and partial thickness tearing are common
      findings. Although postoperative range of motion is correlated to Goutallier
      changes of the infraspinatus, rotator cuff pathology is not correlated to
      outcomes after TSA; therefore, one may proceed with TSA without concern of their
      effect on postoperative outcomes.

PMID- 28751093
TI  - Two-stage reimplantation for the treatment of deep infection after shoulder
      arthroplasty.
AB  - BACKGROUND: Two-stage reimplantation is the most common treatment modality
      considered for periprosthetic shoulder infection (PSI). Most studies to date have
      reported on a relatively small number of shoulders. The purpose of this study was
      to determine the outcome of 2-stage reimplantation for PSI in terms of both
      eradication of infection and restoration of function. METHODS: Between 1980 and
      2010, 40 shoulders (39 patients) underwent a 2-stage reimplantation for PSI; 35
      shoulders (34 patients) met inclusion criteria (10 hemiarthroplasties, 24
      anatomic total shoulder arthroplasties, 1 reverse total shoulder arthroplasty).
      Outcome data included pain, motion, Neer rating, and complications. RESULTS: At
      most recent follow-up (4.1 years), 2-stage reimplantation had resulted in
      significant improvements in pain (from 4.4 to 2 on a 5-point scale; P < .0001),
      mean forward elevation (64 degrees -118 degrees ; P < .0001), and mean external
      rotation (14 degrees -41 degrees ; P < .0001). Preoperative testing showed
      leukocytosis in 1 patient, elevated C-reactive protein concentration in 67%,
      elevated erythrocyte sedimentation rate in 61%, and positive preoperative
      aspiration in 69%. Persistent infection, defined as positive cultures in samples
      obtained at the time of reimplantation, was identified in 5 shoulders (15%); 50%
      of persistent infections grew Propionibacterium acnes. Reoperations for infection
      included irrigation and debridement (1), a second 2-stage reimplantation (2), and
      resection arthroplasty (1); 2 additional patients were treated with chronic
      suppression. Reoperation for aseptic glenoid loosening was performed in 2
      additional shoulders. Results were graded excellent in 10 (28%), satisfactory in
      12 (33%), and unsatisfactory in 13 (39%) shoulders. CONCLUSION: Two-stage
      reimplantation eradicated PSI in 85% of the shoulders. Pain relief and good arcs
      of motion were achieved in many patients, but there was an overall rate of
      unsatisfactory results approaching 40%. Preoperative testing was not always
      reliable for the diagnosis of PSI.

PMID- 28751094
TI  - Revision of failed shoulder hemiarthroplasty to reverse total arthroplasty:
      analysis of 157 revision implants.
AB  - BACKGROUND: There remains a paucity of studies examining the conversion of failed
      hemiarthroplasty (HA) to reverse total shoulder arthroplasty (RTSA). Therefore,
      the purpose of this study was to examine a large series of revision HA to RTSA.
      METHODS: A population of 157 patients who underwent conversion of a failed HA to
      a revision RTSA from 2006 through 2014 were included. The mean follow-up was 49
      months (range, 24-121 months). The indications for revision surgery included
      instability with rotator cuff insufficiency (n = 127) and glenoid wear (n = 30);
      instability and glenoid wear were associated in 38 cases. Eight patients with
      infection underwent 2-stage reimplantation. RESULTS: Patients experienced
      significant improvements in their preoperative to postoperative pain and shoulder
      range of motion (P < .0001), with median American Shoulder and Elbow Surgeons and
      Simple Shoulder Test scores of 60 and 6 points, respectively. There were 11 (7%)
      repeated revision surgeries, secondary to glenoid component loosening (n = 3),
      instability (n = 3), humeral component disassembly (n = 2), humeral stem
      loosening (n = 1), and infection (n = 2). Implant survivorship was 95.5% at 2
      years and 93.3% at 5 years. There were 4 reoperations including axillary nerve
      neurolysis (n = 2), heterotopic ossification removal (n = 1), and hardware
      removal for rupture of the metal cerclage for an acromial fracture (n = 1). At
      final follow-up, there were 5 "at-risk" glenoid components. CONCLUSION: Patients
      experience satisfactory pain relief and recovery of reasonable shoulder function
      after revision RTSA from a failed HA. There was a relatively low revision rate,
      with glenoid loosening and instability being the most common causes.

PMID- 28751095
TI  - A Comprehensive Review of Immunization Practices in Solid Organ Transplant and
      Hematopoietic Stem Cell Transplant Recipients.
AB  - BACKGROUND: Vaccine-preventable diseases, especially influenza, varicella, herpes
      zoster, and invasive pneumococcal infections, continue to lead to significant
      morbidity and mortality in solid organ transplant (SOT) and hematopoietic stem
      cell transplant (HSCT) recipients. METHODS: We highlight guideline
      recommendations for the use of key vaccines in SOT and HSCT recipients and to
      review the latest evidence and developments in the field. RESULTS: Physicians
      should vaccinate individuals with end-stage organ disease, as vaccine
      seroresponse rates are higher pretransplantation. Most live attenuated vaccines
      continue to be contraindicated post-transplantation, but there are emerging
      safety profile and efficacy data to support the use of specific live attenuated
      vaccines, such as measles, mumps, and rubella in pediatric liver or kidney
      transplant recipients who are on low-level maintenance immunosuppression and
      without recent history of allograft rejection. An inactivated subunit varicella
      zoster virus vaccine is currently awaiting US Food and Drug Administration
      approval. While we await the safety profile and efficacy data of this subunit
      vaccine in transplant recipients, it will likely benefit immunocompromised
      individuals, including transplant recipients, because the live attenuated herpes
      zoster vaccine is currently contraindicated in transplant recipients and
      transplantation candidates receiving immunosuppression. CONCLUSIONS: There is
      currently no evidence that vaccines lead to allograft rejection in SOT
      recipients. Household contacts of SOT and HSCT recipients should be vaccinated
      per the Advisory Committee on Immunization Practices schedule and
      recommendations. IMPLICATIONS: Immunizations remain underutilized in
      transplantation patients. Although efficacy of vaccines in SOT and HSCT may be
      suboptimal, partial protection is preferred over no protection.

PMID- 28751096
TI  - Vaccines.

PMID- 28751097
TI  - Corrigendum to "Abstracts Presented at EACPT 2017": Clin Ther 2017;39:e66.

PMID- 28751098
TI  - Patient-reported Quality of Life and Treatment Satisfaction in Patients With
      HR+/HER2- Advanced/Metastatic Breast Cancer.
AB  - PURPOSE: Globally, around 1.67 million new cases of breast cancer are diagnosed
      each year, with advanced breast cancer (ABC-Stage III) and metastatic breast
      cancer (MBC-Stage IV) together accounting for up to 22% of incident cases.
      Hormone receptor-positive/human epidermal growth factor receptor 2-negative
      (HR+/HER2-) breast cancer comprises 66% of ABC/MBC. Understanding disease
      specific health-related quality of life and patient satisfaction with treatments
      currently available for HR+/HER2- ABC/MBC in clinical practice is essential for
      assessing potential unmet need in this patient population. METHODS: Data on
      treatment patterns in patients with HR+/HER2- ABC/MBC were collected from
      oncology practices across the United States and Europe in a cross-sectional study
      in a clinical practice setting, the Adelphi Real World Advanced Breast Cancer
      Disease Specific Programme. A subset of patients included in the study completed
      several self-reported tools, including the Functional Assessment of Cancer
      Therapy-Breast and the Cancer Therapy Satisfaction Questionnaire. Analyses were
      conducted using data from the overall cohort and stratified by current treatment,
      metastatic sites, and number of prior therapy lines. FINDINGS: Overall, 739
      patients were recruited by 173 oncologists; 83% of patients had MBC, with the
      balance having ABC. The majority of patients with MBC had visceral metastases
      without bone metastases, and similar percentages of the total study population
      (~40%) were receiving chemotherapy and endocrine therapy. Patients receiving only
      endocrine therapy had significantly better cancer-specific quality of life than
      did those receiving chemotherapy. Endocrine therapy also associated with fewer
      concerns about side effects and higher treatment satisfaction than chemotherapy.
      Statistically lower scores, indicating poorer well-being, were observed in
      patients with both bone and visceral metastases compared with those with either
      bone-only or visceral-only metastases for all but the Social/Family Well-Being
      and Functional Well-Being domains of the Functional Assessment of Cancer Therapy
      Breast. Patients with bone and visceral metastases had significantly greater
      concerns about treatment side effects than those with metastases at other sites.
      Receipt of a greater number of prior lines of therapy was associated with poorer
      well-being scores. There was a significant negative association between number of
      lines of treatment and treatment expectations. IMPLICATIONS: Findings from this
      study from clinical practice suggest that treatment outcomes in HR+/HER2- ABC/MBC
      could be optimized through improved understanding of the impact that components
      of patient care have on health-related quality of life and treatment
      satisfaction.

PMID- 28751099
TI  - Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting
      Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE
      and CONFIRM.
AB  - PURPOSE: In Phase III studies (DEFINE [Determination of the Efficacy and Safety
      of Oral Fumarate in Relapsing-Remitting MS]/CONFIRM [Comparator and an Oral
      Fumarate in Relapsing-Remitting Multiple Sclerosis]), delayed-release dimethyl
      fumarate (DMF) demonstrated significant efficacy and a favorable benefit-risk
      profile in patients with relapsing-remitting multiple sclerosis (RRMS). Post hoc
      analyses of integrated data from DEFINE/CONFIRM were conducted to evaluate the
      effect of DMF in patients previously treated with interferon (IFN) beta. METHODS:
      Patients (age 18-55 years; Expanded Disability Status Scale score, 0-5.0) were
      randomized to receive DMF 240 mg BID or TID, placebo, or glatiramer acetate
      (CONFIRM only) for up to 2 years. Previous IFN users received at least 1 IFN
      treatment >3 months before randomization. Data for DMF 240 mg BID (approved
      dosing regimen) are reported. FINDINGS: In the integrated intention-to-treat
      population, 172 and 169 patients receiving DMF or placebo, respectively, had
      received >=1 prior IFN. In this subgroup, significant reductions with DMF versus
      placebo were observed for the annualized relapse rate (rate ratio, 0.55 [95% CI,
      0.40-0.77]), new/newly enlarging T2-hyperintense lesions (lesion mean ratio, 0.16
      [95% CI, 0.09-0.29]), odds of having more gadolinium-enhancing lesions (odds
      ratio, 0.17 [95% CI, 0.07-0.44]), and new T1-hypointense lesions (lesion mean
      ratio, 0.25 [95% CI, 0.14-0.45]). Median Expanded Disability Status Scale scores
      remained stable during the study period. Adverse events associated with DMF
      included flushing and gastrointestinal events. IMPLICATIONS: In this post hoc
      analysis in patients with previous IFN treatment, DMF demonstrated significant
      efficacy over 2 years versus placebo and an adverse event profile consistent with
      the overall population of DEFINE/CONFIRM. ClinicalTrials.gov identifiers: DEFINE,
      NCT00420212; and CONFIRM, NCT00451451.

PMID- 28751100
TI  - Reply to Bowman et al.: Building the foundations for moving mu suppression
      research forward.

PMID- 28751101
TI  - Association of handgrip strength with B-type natriuretic peptide levels and
      cardiovascular events in patients with type 2 diabetes.

PMID- 28751102
TI  - [Promoting directives of the Quality Law of the Spanish National Health System:
      Computer-interpretable clinical practice guidelines].
AB  - The Cohesion and Quality Act of the National Health System promotes the use of
      new technologies to make it possible for health professionals put the scientific
      evidence into practice. In order to do this, there are technological tools, known
      as of computer-interpretable guidelines, which can help achieve this goal from an
      innovation perspective. They can be adopted using an iterative process, having a
      great initial potential as an educational tool, of quality and safety of the
      patient, in the decision making and, optionally, can be integrated with the
      electronic medical history, once they are rigorously validated. This article
      presents updates on these tools, reviews international projects, and personal
      experiences in which they have demonstrated their value, and highlights the
      advantages, risks, and limitations they present from a clinical point of view.

PMID- 28751103
TI  - [Prevalence and characterization of overactive bladder detected in a population
      in Madrid with self-administered OAB-V3 questionnaire in Primary Care].
AB  - OBJECTIVE: Determining the prevalence of symptoms suggestive of overactive
      bladder (OAB) in a Spanish population and evaluate the impact of these symptoms
      on well-being and labour productivity in this population. DESIGN: Transversal
      study. LOCATION: Primary health care, Madrid, Spain. PARTICIPANTS: Males and
      females >30 years. INTERVENTIONS: Classification by primary care physicians with
      the Overactive Bladder Awareness Tool abbreviated version (OAB-V3). Subjects with
      score >=3 and a similarly balanced control population with score <3 were
      clinically investigated. PRINCIPAL MEASUREMENTS: History, physical examination,
      urinalysis, sonography, general well-being scale and the questionnaires PPBC, OAB
      q y WPAI-SHP. RESULTS: A total 923 subjects were screened, of which 209 (22.6%),
      35% males and 65% females, had probable OAB. Age distribution increased from
      11.1% in 4th decade to 44.4% in 9th decade. Kappa coefficient between suspected
      OAB and definite diagnosis was .83. The area under ROC curve for diagnosis based
      on OAB-V3 questionnaire and the presence of perceived bother and coping
      strategies was 92%. Subjects classified by score >=3 had worse well-being, higher
      PPBC score and worse parameters on total OAB-q and transformed scores for each
      OAB-q subscale (P<.0001). In these subjects labour productivity was not affected
      (P=.14) but the capacity to perform regular activities was (P<.0001).
      CONCLUSIONS: OAB-V3 is a simple questionnaire to screen OAB with good predictive
      accuracy in a primary care setting and reveals important implications on health
      related quality of life issues.

PMID- 28751104
TI  - Myofibroblastic, fibroblastic and myoid lesions of the breast.
AB  - Myofibroblastic, fibroblastic and/or myoid lesions are rare in the breast but
      comprise the majority of mammary mesenchymal spindle cell lesions. Whereas most
      have similar features to their counterparts at extramammary sites,
      pseudoangiomatous stromal hyperplasia is considered a breast-specific
      myofibroblastic proliferation on the same spectrum as myofibroblastoma. Other
      lesions with myofibroblastic/fibroblastic differentiation include fibromatosis
      and nodular fasciitis, as well as more aggressive tumors such as the rarely
      reported myofibrosarcoma, inflammatory myofibroblastic tumor and fibrosarcoma.
      Lesions with myoid differentiation include benign leiomyoma, myoid hamartoma and
      leiomyomatous myofibroblastoma, but primary leiomyosarcoma and rhabdomyosarcoma
      may also rarely arise in the breast. Furthermore, fibroepithelial lesions and
      metaplastic carcinomas can demonstrate myoid metaplasia. Diagnosis can be
      challenging, particularly on core biopsy, but benign lesions with or without
      recurrence potential must be distinguished from more aggressive tumors,
      especially metaplastic carcinoma and phyllodes tumors. This article will review
      lesions with myofibroblastic, fibroblastic and myoid differentiation in the
      breast, with special emphasis on differential diagnosis.

PMID- 28751105
TI  - Permissiveness of human hepatocellular carcinoma cell lines for hepatitis C virus
      entry and replication.
AB  - Hepatitis C virus (HCV) is a globally prevalent pathogen and is associated with
      high death rates and morbidity. Since its discovery in 1989, HCV research has
      been impeded by the lack of a robust infectious cell culture system and thus in
      vitro studies on diverse genetic backgrounds are hampered because of the limited
      number of hepatoma cell lines which are able to support different aspects of the
      HCV life cycle. In the current study, we sought to expand the limited number of
      permissive cells capable of supporting the diverse phases of the HCV life cycle.
      Initially, we screened a panel of new hepatoma-derived cell lines, designated
      BCLC-1, -2, -3, -4, -5, -6, -9 and -10 cells, for their ability to express
      essential HCV receptors and subsequently to support HCV entry by using the well
      characterized HCV pseudoparticle system (HCVpp). Apart from BCLC-9, all BCLC cell
      lines were permissive for HCVpp infection. Next, BCLC cells were subjected to
      short- and long-term HCV RNA replication studies using HCV subgenomic replicons.
      Interestingly, only BCLC-1, -5 and -9 cells, supported short-term HCV RNA
      replication, but the latter were excluded from further studies since they were
      refractory for HCV entry. BCLC-1, -5 were able to support long-term HCV
      replication too; yet BCLC-5 cells supported the highest long-term HCV RNA
      replication levels. Furthermore, cured BCLC-5 clones from HCV subgenomic
      replicon, showed increased permissiveness for HCV RNA replication. Strikingly, we
      were unable to detect endogenous BCLC-5 miR122 expression - an important HCV host
      factor- and as expected, the exogenous expression of miR122 in BCLC-5 cells
      increased their permissiveness for HCV RNA replication. However, this cell line
      was unable to produce HCV infectious particles despite ectopic expression of
      apolipoprotein E, which in other hepatoma cell lines has been shown to be
      sufficient to enable the HCV secretion process, suggesting a lack of other host
      cellular factor(s) and/or the presence of inhibitory factor(s). In conclusion,
      the establishment of these new permissive cell lines for HCV entry and
      replication, which possess a different genetic background compared to the well
      established models, expands the current repertoire of hepatoma cell lines
      susceptible to the study of the HCV life cycle and also will aid to further
      elucidate the cellular determinants that modulate HCV replication, assembly and
      egress.

PMID- 28751106
TI  - Altmetrics: A Measure of Social Attention toward Scientific Research.
AB  - The quality and impact of scientific research is traditionally measured by
      citation-based metrics. However, the internet and social media revolution has led
      to radical changes in the way scientific information is shared and how it impacts
      the world. Alternative metrics (altmetrics) is a rapidly evolving measure to
      quantify social media attention received by a scientific work. It is a complement
      to the conventional metrics, and has tremendous potential in enabling faster
      alternative ways of evaluating research impact. We discuss the Altmetric Score
      and the growing role of altmetrics for measuring research impact.

PMID- 28751107
TI  - Corrigendum to "Zerumbone enhances the Th1 response and ameliorates ovalbumin
      induced Th2 responses and airway inflammation in mice" [Int. Immunopharmacol. 24
      (2015) 383-391].

PMID- 28751108
TI  - Processing of mutant N-acetyl-alpha-glucosaminidase in mucopolysaccharidosis type
      IIIB fibroblasts cultured at low temperature.
AB  - BACKGROUND: The autosomal recessive, neurodegenerative disorder
      mucopolysaccharidosis type IIIB (MPSIIIB) is caused by a deficiency of the
      lysosomal enzyme N-acetyl-alpha-glucosaminidase (NAGLU), resulting in
      accumulation of heparan sulfate. The disease spectrum comprises a severe, rapidly
      progressing (RP) phenotype and a more attenuated, slowly progressing (SP)
      phenotype. Previous studies showed significantly higher NAGLU activity in skin
      fibroblasts of SP patients when cultured at 30 degrees C which may be relevant
      for development of novel therapeutic strategies. Here we report on the processes
      involved in this phenomenon. METHODS: Fibroblasts from controls, one RP patient
      (homozygous for the p.R297* mutation) and three SP MPSIIIB patients (homozygous
      for the mutation p.S612G or p.R643C, or compound heterozygous for the mutations
      p.A72_G79dup8 and p.R565Q) were cultured at temperatures ranging from 37 degrees
      C to 27 degrees C and harvested at different time points to assess NAGLU
      activity, mRNA and protein levels, and NAGLU glycosylation. Intracellular
      localization of wild-type and mutant mCherry-tagged NAGLU was analyzed by
      immunofluorescence. RESULTS: In control fibroblasts NAGLU was present as a 85kDa
      precursor and a 82kDa mature form. In SP patients' fibroblasts cultured at 37
      degrees C, only the 85kDa form was detected. Culturing at lower temperatures
      resulted in higher NAGLU mRNA levels, increased levels of both precursor and
      mature NAGLU protein and improved processing. The formation of mature NAGLU
      corresponded with higher NAGLU activity levels. CONCLUSION: We show that the
      NAGLU protein consists of a precursor and a mature form and that in SP MPSIIIB
      patients' fibroblasts only the precursor protein is present at 37 degrees C.
      Culturing at lower temperatures resulted in the formation of the mature,
      enzymatically active form, due to higher mRNA levels and improved processing.

PMID- 28751109
TI  - Polymorphism and peptide-binding specificities of porcine major
      histocompatibility complex (MHC) class I molecules.
AB  - The swine lymphocyte antigen class I (SLA I) is a highly polymorphic gene
      superfamily that plays an important role in swine anti-viral immune responses.
      However, an understanding of the highly variable sites and peptide-binding
      specificities of SLA I molecule is limited. In this study, a total of 27 SLA I
      alleles were identified from 3 Tibetan wild boars and 3 Heishan pigs. The
      phylogenetic relationship between the Tibetan wild boar and other breeds was
      analyzed using bioinformatics methods, and the highly variable sites were noted
      in the three dimensional structures of SLA I. Peptides from the porcine
      reproductive and respiratory syndrome virus (PRRSV) and influenza A virus (IAV)
      were screened with a bioinformatic method and refolding assay in vitro. The
      superior SLA I molecules, which have the ability to combine with more peptides,
      were selected from the Tibetan wild boars and Heishan pigs. The results showed
      that the SLA I of the Tibetan wild boars was not divergent from other pig breeds
      and that high-variation sites were mostly located in the peptide binding groove
      (PBG), suggesting that high variation sites could determines the peptide-binding
      characteristics and would possibly influences peptide-specific CD8+ T cell
      recognition. The SLA I allele SLA-1*0302 (known as KY113114) of the Tibetan wild
      boar formed stable complexes with three PRRSV peptides, and the SLA-3*hs0202
      (KJ555032) from Heishan pigs was able to bind with four IAV peptides. The results
      from this study may benefit vaccine development and may help control IAV and
      PRRSV in swine.

PMID- 28751110
TI  - Chronic arthritis in chikungunya virus infection.
AB  - INTRODUCTION: Chikungunya virus infection causes arthralgia and arthritis in the
      acute phase of the disease but, in more than half of the cases, musculoskeletal
      manifestations can be prolonged over time and, in some cases, become chronic.
      Although polyarthralgia is the most frequent chronic manifestation, forms with
      polyarthritis, tenosynovitis and enthesopathy are also common. OBJECTIVE: To
      analyze the clinical characteristics of patients with persistent articular
      manifestations after infection with the Chikungunya virus. PATIENTS: Report of 3
      cases of chronic arthritis after infection with chikungunya virus diagnosed at
      outpatient care in a university hospital of Catalonia, all of them imported after
      exposure in areas of epidemic infection between 2013-2015. RESULTS: All three
      patients had inflammatory joint pain for more than one year after acute disease
      (3, 2 and 1 years, respectively). In all cases, it appeared as polyarthritis with
      involvement of small joints of hands and feet (pseudorheumatoid arthritis-like).
      Laboratory tests showed a slight elevation of acute phase reactants, and analyses
      for immune markers were negative. Two of the patients required treatment with
      glucocorticoids and hydroxychloroquine. The course led to slow clinical
      improvement, but only one of them came to be completely asymptomatic. CONCLUSION:
      In the differential diagnosis of chronic polyarthritis, Chikungunya virus disease
      should also be considered in areas in which it is not endemic.

PMID- 28751111
TI  - Gustatory receptor 22e is essential for sensing chloroquine and strychnine in
      Drosophila melanogaster.
AB  - Chloroquine, an amino quinolone derivative commonly used as an anti-malarial
      drug, is known to impart an unpleasant taste. Little research has been done to
      study chloroquine taste in insects, therefore, we examined both the deterrant
      properties and mechanisms underlying chloroquine perception in fruit flies. We
      identified the antifeedant effect of chloroquine by screening 21 gustatory
      receptor (Grs) mutants through behavioral feeding assays and electrophysiology
      experiments. We discovered that two molecular sensors, GR22e and GR33a, act as
      chloroquine receptors, and found that chloroquine-mediated activation of GRNs
      occurs through S-type sensilla. At the same time, we successfully recapitulated
      the chloroquine receptor by expressing GR22e in ectopic gustatory receptor
      neurons. We also found that GR22e forms a part of the strychnine receptor. We
      suggest that the Drosophila strychnine receptor might have a very complex
      structure since five different GRs are required for strychnine-induced action
      potentials.

PMID- 28751112
TI  - HIV Status Disclosure in the Workplace: Positive and Stigmatizing Experiences of
      Health Care Workers Living with HIV.
AB  - We explored workplace experiences of 10 health care providers with HIV in the
      Netherlands. We used semi-structured interviews to discuss motivations for
      disclosure and concealment, reactions to disclosures, the impact of reactions,
      and coping with negative reactions. Reasons for disclosure were wanting to share
      the secret, expecting positive responses, observing positive reactions to others,
      wanting to prevent negative reactions, and being advised to disclose. Reasons for
      concealment included fearing negative reactions, observing negative reactions,
      previous negative experiences, having been advised to conceal, and considering
      disclosure unnecessary. Positive reactions included seeing HIV as a nonissue;
      showing interest, support, and empathy; and maintaining confidentiality. Negative
      reactions included management wanting to inform employees, work restrictions,
      hiring difficulties, gossip, and hurtful comments, resulting in participants
      being upset, taken aback, angry, depressed, or feeling resignation. Participants
      coped by providing information, standing above the experience, attributing
      reactions to ignorance, seeking social support, or leaving their jobs.

PMID- 28751113
TI  - Tissue Engineering in Hand Surgery: A Technology Update.
AB  - The field of hand surgery is constantly evolving to meet the challenges of
      repairing intricate anatomical structures with limited availability of donor
      tissue. The past 10 years have seen an exponential growth in tissue engineering,
      which has broadened the perspectives of tackling these age-old problems. Various
      fabrication techniques such as melt electrospinning and fused deposition
      modelling have been employed to synthesize 3-dimensional bioscaffolds that can be
      used to replace lost tissue. These bioscaffolds with strategic biomimicry have
      been shown to allow for integrative and functional repair of tissue injuries.
      This review article summarizes the most current advances in tissue engineering
      and its applications in the field of hand surgery. It outlines the current tissue
      engineering techniques commonly used for tackling musculoskeletal problems and
      highlights the most promising approaches according to clinical evidence. In
      particular, the paper explores regenerative medicine concepts applied to specific
      tissues including nerve, bone, cartilage, tendon, ligament, and vessels. In the
      face of innovative and pioneering research, tissue engineering will undoubtedly
      play a key role in reconstructive hand surgery in the not too distant future.

PMID- 28751114
TI  - [Post-partum depressive symptoms: Prevalence, risk factors and relationship with
      quality of life].
AB  - OBJECTIVE: The objective of our study was to estimate the prevalence of the post
      partum depressive symptomatology in a sample of Tunisian women, to study
      associated factors and to assess its relationship to quality of life. PATIENTS
      AND METHODS: This is a prospective study carried out in two stages: during the
      first week (T1), then between sixth and eighth week post-partum (T2). Depressive
      symptomatology and quality of life were assessed respectively by the Edinburgh
      Postnatal Depression Scale and the World Health Organization Quality of Life
      scale. RESULTS: In the first stage, the prevalence of depressive symptomatology
      in the total sample (150 women) was 14.7% and was related to age above 35 years,
      low school level, personal psychiatric history, multiparity, caesarean delivery
      or forceps in the previous pregnancy and unplanned pregnancy. This prevalence was
      19.8% among the 126 women reviewed in T2 and was correlated with the exaggerated
      sympathetic signs during pregnancy, namely perversion of taste and fatigue.
      Quality of life was strongly correlated with depressive symptoms in T1 and T2.
      CONCLUSION: Post-partum depressive symptoms were common in our sample and were
      correlated with quality of life. Therapeutic measures should be proposed for
      women with post-partum depressive symptoms and particularly with several risk
      factors in order to improve their quality of life.

PMID- 28751115
TI  - Comment on data sparsity - Diagnostic and prognostic significance of systemic
      alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study.

PMID- 28751116
TI  - Monoamine oxidase B oxidizes a novel multikinase inhibitor KW-2449 to its iminium
      ion and aldehyde oxidase further converts it to the oxo-piperazine form in human.
AB  - (E)-1-{4-[2-(1H-Indazol-3-yl)vinyl]benzoyl}piperazine (KW-2449) is a novel
      multikinase inhibitor. During our clinical study, we found that KW-2449 is mainly
      metabolized to its oxo-piperazine form (M1). An inhibition study suggested that
      monoamine oxidase-B (MAO-B) oxidizes KW-2449 to an iminium (intermediate) and
      aldehyde oxidase (AO) then metabolizes the intermediate to M1. The conversion of
      KW-2449 to the iminium (intermediate) by MAO-B was confirmed by the formation of
      its cyanide adduct. This cooperative metabolic pathway by MAO-B and AO was newly
      identified in the metabolism of piperazine. The clearance of KW-2449 by MAO-B and
      AO in human was estimated based on the kinetic analysis with in vitro-in vivo
      extrapolation. The systemic clearance in human was similar to the calculated
      value, indicating that the extrapolation approach was applicable to KW-2449
      metabolism. Finally, we found that (E)-3-amino-1-{4-[2-(1H-Indazol-3
      yl)vinyl]benzoyl}-pyrrolidine (Compound A) as a stable compound against MAO-B and
      AO. The total body clearance of Compound A was reduced to one tenth of KW-2449,
      demonstrating that preventing the metabolism of MAO and AO led to more preferable
      pharmacokinetic profiles. As piperazine is often introduced to drug candidates to
      improve lipophilicity of the compound to get more hydrophilic nature, the results
      of this study provide useful information for future drug development.

PMID- 28751117
TI  - Single agent trabectedin in heavily pretreated patients with recurrent ovarian
      cancer.
AB  - PURPOSE: In 2012, due to a shortage of pegylated liposomal doxorubicin, single
      agent trabectedin was proposed as an alternative of treatment to our patients
      with recurrent ovarian cancer (ROC) at our center. The aim of this retrospective
      study was to evaluate efficacy and tolerability of trabectedin in this context.
      PATIENTS AND METHODS: This retrospective study included all patients who received
      intravenous trabectedin 1.3mg/m2 over 3h every 3weeks for ROC between January
      2012 and December 2015 at the Centre hospitalier de l'Universite de Montreal. The
      primary outcome was the progression-free survival (PFS) based on CA-125 levels,
      clinical exam and/or Response Evaluation Criteria in Solid Tumors criteria. We
      also evaluated overall survival (OS), response rate and toxicities. RESULTS: A
      total of 42 patients with a median age of 59years received trabectedin in 2nd or
      3rd line (12% of patients), 4th or 5th line (43%), and >=6 lines (45%) and 45%
      were platinum-resistant. The median number of cycles received was 6 (range 1
      19cycles). Complete response (CR), partial response (PR), stable disease (SD) and
      progression occurred in 19%, 29%, 33% and 19% of patients, respectively. The
      median PFS and OS was 4.3months (95% CI, 3.4-5.1) and 16.2months (95% CI, 9.0
      23.5), respectively. In patients with a clinical benefit (CR, PR, SD), the median
      PFS was 4.6months. Trabectedin was well tolerated with few adverse events.
      CONCLUSION: Our results demonstrate that trabectedin has an interesting efficacy
      as a single agent in heavily treated ROC patients.

PMID- 28751118
TI  - Description of a reproducible anatomically based surgical algorithm for detection
      of pelvic sentinel lymph nodes in endometrial cancer.
AB  - OBJECTIVE: To describe and evaluate a reproducible, anatomically based surgical
      algorithm, including reinjection of tracer to enhance technical success rate, for
      detection of pelvic sentinel lymph nodes (SLNs) in endometrial cancer (EC).
      METHODS: A prospective study of 102 consecutive women with high risk EC scheduled
      for robotic surgery was conducted. Following cervical injection of a fluorescent
      dye, an algorithm for trans- and retroperitoneal identification of tracer display
      in the lower and upper paracervical pathways was strictly adhered to. To enhance
      the technical success rate, this included ipsilateral reinjection of tracer in
      case of non-display of any lymphatic pathway. The lymphatic pathways were kept
      intact by opening the avascular planes. To minimize disturbance from leaking dye,
      removal of SLNs was first performed along the lower paracervical (presacral)
      pathways followed by the more caudal upper paracervical pathways. In each
      pathway, the juxtauterine node with an afferent lymph vessel was defined as an
      SLN. After removal of SLNs, a complete pelvic and, unless contraindicated,
      infrarenal paraaortic lymph node dissection was performed. RESULTS: The bilateral
      detection rate including tracer reinjection was 96%. All 24 (23.5%) node positive
      patients had at least one metastatic SLN. Presacral lymph node metastases were
      discovered in 33.3% of the node positive patients. One patient (4.2%) had an
      isolated presacral lymph node metastasis. CONCLUSIONS: The described cranial-to
      caudal anatomically based surgical SLN algorithm, including a presacral
      dissection and reinjection of tracer, results in a high SLN detection rate and
      identified all patients with lymph node metastases.

PMID- 28751119
TI  - Utilization of intraperitoneal chemotherapy for optimally cytoreduced advanced
      stage epithelial ovarian cancer: A 10-year single institution experience with a
      racially diverse urban population.
AB  - OBJECTIVES: The goal of our study was to define utilization and clinical results
      of intraperitoneal (IV/IP) compared to intravenous (IV) chemotherapy in a
      racially and ethnically diverse population with optimally debulked advanced stage
      epithelial ovarian cancer. METHODS: After IRB approval, all patients diagnosed
      with epithelial ovarian cancer that underwent primary cytoreductive surgery at
      our institution from 2005 to 2016 were identified. Death was verified by the
      National Social Security Death Index. Patients who received at least one IV/IP
      cycle were analyzed in the IV/IP cohort. Kaplan-Meier and Cox proportional
      hazards models were performed. RESULTS: 96 patients with advanced stage optimally
      cytoreduced epithelial ovarian cancer (median follow up 33months) were
      identified. 51% and 49% of patients received IV/IP and IV chemotherapy,
      respectively. 27%, 22%, and 39% of patients were of white, black, and other race.
      Compared with IV chemotherapy only, IV/IP chemotherapy was associated with longer
      OS (log rank <0.002) and IV/IP chemotherapy versus IV chemotherapy alone was
      associated with a lower risk of death (HR=0.31, 95% CI 0.16-0.62, P<0.001). The
      median overall survival for the IV/IP and IV groups was 76months (95% CI 62 - not
      estimated) and 38months (95% CI 30-55), respectively. There was a trend toward
      higher risk of death for patients who completed fewer than 6cycles of IV/IP
      chemotherapy compared to women who completed 6 IV/IP cycles (HR=3.2, 95% CI 0.98
      9.27 (P=0.05). No differences in patient or tumor characteristics were identified
      between these two groups of patients. CONCLUSIONS: In our racially diverse urban
      patients, 50% of patients received IV/IP chemotherapy and it was associated with
      improved overall survival compared to IV chemotherapy alone. Further
      investigation is needed to identify barriers to use of IV/IP chemotherapy.

PMID- 28751120
TI  - Horizontal Gene Transfer and Ecosystem Function Dynamics.
AB  - Horizontal gene transfer can provide bacteria with new functions that confer an
      important competitive advantage, and is therefore likely to affect the dynamics
      of bacterial ecosystems. Two studies by Wolfe et al. and Bonham et al. prepare
      the way to study this hypothesis in a model ecosystem with reproducible
      properties.

PMID- 28751121
TI  - Autocatalytic networks in cognition and the origin of culture.
AB  - It has been proposed that cultural evolution was made possible by a cognitive
      transition brought about by onset of the capacity for self-triggered recall and
      rehearsal. Here we develop a novel idea that models of collectively autocatalytic
      networks, developed for understanding the origin and organization of life, may
      also help explain the origin of the kind of cognitive structure that makes
      cultural evolution possible. In this setting, mental representations (for
      example, memories, concepts, ideas) play the role of 'molecules', and 'reactions'
      involve the evoking of one representation by another through remindings and
      associations. In the 'episodic mind', representations are so coarse-grained
      (encode too few properties) that such reactions must be 'catalyzed' by external
      stimuli. As cranial capacity increased, representations became more fine-grained
      (encoded more features), which facilitated recursive catalysis and culminated in
      free-association and streams of thought. At this point, the mind could combine
      representations and adapt them to specific needs and situations, and thereby
      contribute to cultural evolution. In this paper, we propose and study a simple
      and explicit cognitive model that gives rise naturally to autocatalytic networks,
      and thereby provides a possible mechanism for the transition from a pre-cultural
      episodic mind to a mimetic mind.

PMID- 28751122
TI  - Inhalation injury caused by cornstarch dust explosion in intubated patients-A
      single center experience.
AB  - BACKGROUND: Around 10%-20% of burned patients have inhalation injuries, and the
      severity of these injuries is correlated with mortality. Fiberoptic bronchoscopy
      is an important tool for the early diagnosis of inhalation injury. This study
      investigated correlations between the severity of inhalation injury and outcomes
      of patients involved in a cornstarch dust explosion in northern Taiwan in 2015.
      METHODS: Patients with burns who were intubated after the explosion were
      enrolled. Their medical records were reviewed, and data including patient
      characteristics, percentage of total body surface area (%TBSA) burned, severity
      of the inhalation injury, mechanical ventilation settings, and outcomes were
      collected and analyzed. RESULTS: Twenty patients underwent fiberoptic
      bronchoscopy during the first 24h to evaluate an inhalation injury. Their mean
      age was 22.4+/-5.5 years and the mean %TBSA burned was 55.7+/-19.4%. Fourteen
      patients had a grade 1 inhalation injury and six had a grade 2 injury. There was
      a higher %TBSA burned in the grade 1 group than in the grade 2 group, although
      the difference did not reach statistical significance (60.0+/-20.3% versus 45.5+/
      13.5%, p=0.129). Compared to the grade 2 group, the grade 1 group had a
      significantly higher white blood cell count (29.4+/-9.3 versus 18.6+/-4.6,
      p=0.015) and frequency of facial burns (85.7% versus 33.3%, p=0.037). The overall
      intensive care unit mortality rate was 10% (n=2), with no significant intergroup
      difference (grade 1, 14.3% versus grade 2, 0%, p=0.192). CONCLUSION: Although the
      explosion resulted in a high rate of inhalation injuries in critically ill
      patients, there was no significant correlation between mortality and the severity
      of the inhalation injuries.

PMID- 28751123
TI  - Down Syndrome and Pediatric Nonalcoholic Fatty Liver Disease: A Causal or Casual
      Relationship?

PMID- 28751124
TI  - Leisure Time Physical Activity in Young Adults Born Preterm.
AB  - OBJECTIVE: To evaluate the amount of self-reported physical activity in young
      adults born prematurely compared with those born at term. STUDY DESIGN:
      Unimpaired participants of the Preterm Birth Study (Preterm Birth and Early Life
      Programming of Adult Health and Disease) birth cohort study were studied at age
      23.3 +/- 1.2 (SD) years: 118 born early preterm (<34 weeks), 210 late preterm (34
      36 weeks), and 311 born at term (>=37 weeks, controls). The participants
      completed a validated 30-item, 12-month physical activity questionnaire. The
      annual frequency and total volume of conditioning and nonconditioning leisure
      time physical activity and commuting physical activity were calculated and the
      data analyzed by means of linear regression. RESULTS: Adults born early preterm
      reported a 31.5% (95% CI, 17.4-43.2) lower volume of leisure time physical
      activity (in metabolic equivalents [MET] h/year) and had a 2.0-fold increased OR
      (1.2-3.3) of being in the least active quintile than controls. Lower amounts of
      conditioning, nonconditioning, and commuting physical activity all contributed to
      the difference. In addition, early preterm participants undertook less vigorous
      physical activity (>=6 MET). No differences in physical activity were found
      between the late preterm and control groups. Adjustments for potential early life
      confounders and current mediating health characteristics did not change the
      results. CONCLUSIONS: Young adults born early preterm engage less in leisure time
      physical activities than peers born at term. This finding may in part underlie
      the increased risk factors of cardiometabolic and other noncommunicable diseases
      in adults born preterm. Low physical activity is a risk factor for several
      noncommunicable diseases and amenable to prevention.

PMID- 28751125
TI  - Caregiver-Reported Quality of Life in Youth with Down Syndrome.
AB  - OBJECTIVES: To describe caregiver-reported quality of life (QOL) in youth with
      Down syndrome (DS) and to examine the role of obesity on QOL. STUDY DESIGN:
      Caregivers of youth with and without DS aged 10 through 20 years completed
      questionnaires examining QOL (Pediatric Quality of Life Questionnaire) and weight
      related QOL (Impact of Weight on Quality of Life - Kids). Age- and sex-specific z
      scores were generated for body mass index. Obesity was defined as a body mass
      index >=95th percentile for age and sex. RESULTS: Caregiver-reported Total QOL,
      Physical Health, and Psychosocial Health summary scores were all lower in the DS
      group compared with the non-DS controls (P < .001). Social and School Functioning
      were also lower (P < .001), but Emotional Functioning did not differ between DS
      and non-DS groups (P = .31). Physical Functioning (P = .003) and Total scores (P
      = .03) differed between youth without DS with and without obesity, but no
      differences were reported between youth with DS with and without obesity. On the
      Impact of Weight on Quality of Life - Kids, caregivers of youth with DS reported
      greater Body Esteem (P = .020) and Social Life scores (P = .03) than caregivers
      of non-DS youth. Caregivers of youth with obesity, regardless of DS status,
      reported significantly lower weight-specific QOL scores than caregivers of youth
      without obesity. CONCLUSION: Caregivers reported lower QOL in youth with DS
      compared with youth without DS with the exception of emotional functioning.
      Obesity influences most domains of weight-related QOL in youth with and without
      DS; therefore, providers should address weight concerns in youth with obesity
      even in the presence of DS. CLINICAL TRIAL REGISTRATION: NCT01821300.

PMID- 28751126
TI  - Intracellular Ca2+ is an essential factor for cell damage induced by unsaturated
      carbonyl compounds.
AB  - The unsaturated carbonyl compounds are known as the environmental pollutants.
      Acrolein (ACR) and methyl vinyl ketone (MVK) are representative unsaturated
      carbonyl compounds. ACR is contained in smoke, automobile exhaust, industrial
      waste, and several foods. MVK is widely used as the industrial chemical. Although
      ACR and MVK are highly toxic, the molecular mechanism for their cytotoxicity has
      been unclear. We have previously reported that ACR and MVK are major cytotoxic
      compounds in the gas phase of cigarette smoke, and protein kinase C (PKC)
      inhibitor and NADPH oxidases inhibitor partially rescued cells from ACR- or MVK
      induced cell death (Noya et al., Toxicology, 314, 1-10, 2013). PKC translocation,
      which is hallmark for PKC activation, and cell damage were induced by treatment
      of cultured cells with ACR or MVK. Intracellular Ca2+ chelator completely
      suppressed ACR- or MVK-induced PKC translocation to the cell membrane and cell
      damage, while extracellular Ca2+ chelator had no effects on ACR- and MVK-induced
      cytotoxicity. These results suggest that intracellular Ca2+ is an essential
      factor for cell damage caused by both PKC-dependent and PKC-independent pathways,
      and mobilization of Ca2+ from intracellular Ca2+ stores is induced by ACR or MVK.

PMID- 28751127
TI  - Isolation of six novel 7-oxo- or urso-type secondary bile acid-producing bacteria
      from rat cecal contents.
AB  - Understanding the dynamics of secondary bile acid (SBA) formation in the gut by
      SBA-producing bacteria is important for host health, as SBAs have been shown to
      affect host pathophysiology and gut microbiota composition. However, our
      knowledge of SBA producers is limited in light of the diversity of gut microbes.
      Here, we isolated six novel SBA-producing bacteria from rat cecal contents, all
      of which were members of known species of gut microbes. Anaerostipes caccae D10,
      Bacteroides nordii C5, Clostridioides difficile D7, and Clostridium cadaveris G11
      were capable of oxidizing cholic acid and chenodeoxycholic acid into 7-oxo
      derivatives with varying yields. B. nordii C5 and its type strain JCM 12987T had
      the highest molar yield, ~90%. Clostridium disporicum F4 and Clostridium
      subterminale C4 epimerized cholic acid into ursocholic acid with yields of ~85%;
      the corresponding type strains lacked epimerization activity. Furthermore,
      although not novel as an SBA producer, Clostridium scindens G10 that produced
      deoxycholic acid from cholic acid was isolated for the first time from rodents.
      These findings will contribute to elucidation of SBA formation in the gut.

PMID- 28751129
TI  - Associations of psychotic-like or manic-like experiences with later psychiatric
      disorders: An 11-year follow-up study of middle-aged adults.
AB  - Psychotic-like experiences (PLEs) and manic-like experiences (MLEs) have been
      found to be associated with elevated risk for future psychotic disorders.
      However, most follow-up studies have been conducted on adolescent and young adult
      samples leaving the predictive value of PLEs and MLEs among middle-aged subjects
      largely unknown. Here we report findings of an 11-year follow-up study of middle
      aged subjects with PLEs (n=86) or MLEs (n=45) at baseline and population controls
      (n=62). We found that PLEs or MLEs at baseline did not predict conversion to
      psychosis during an 11-year follow-up in this age group. However, MLEs at
      baseline were associated with increased risk of nonpsychotic psychiatric
      disorders at follow-up whereas PLEs were not. Baseline neuropsychological
      performance was not associated with later psychiatric disorders in groups with
      PLEs or MLEs. In conclusion, our results suggest that among middle-aged subjects
      having PLEs or MLEs may not be a similar risk for future psychotic disorders as
      in younger age groups. However, studies with larger study groups and longer
      follow-up periods are needed in the future.

PMID- 28751128
TI  - Trajectories of schizotypy and their emotional and social functioning: An 18
      month follow-up study.
AB  - Schizotypy is a set of personality traits that convey liability to develop
      schizophrenia. Studying schizotypy in healthy individuals may facilitate the
      understanding of the psychopathological processes underlying schizophrenia. The
      present study aimed to examine the developmental trajectories of schizotypy over
      time using a longitudinal study design. The Chapman Scales for Psychosis
      Proneness were administered to 1541 college students at baseline, and
      subsequently at six-monthly intervals up to 18months. Latent class growth
      analysis was conducted to track the different trajectories. In addition, self
      reported scales were used to measure idea of reference, emotional experiences and
      expression, stress and coping, as well as social functioning. We identified four
      latent classes with distinct trajectories: "nonschizotypy" group (LC1), "stable
      high schizotypy" group (LC3), "high reactive schizotypy" group (LC2) and "low
      reactive schizotypy" group (LC4). These findings suggest that there may be
      distinct developmental trajectories for schizotypy. Two groups may be of
      particular interest: the "stable high schizotypy" group that displayed the worst
      clinical and functioning outcomes on almost all measures and the "high reactive
      schizotypy" group characterized by a relatively rapid decline in functioning.

PMID- 28751130
TI  - In vivo gamma-aminobutyric acid and glutamate levels in people with first-episode
      schizophrenia: A proton magnetic resonance spectroscopy study.
AB  - BACKGROUND: Gamma-aminobutyric acid (GABA) dysfunction and its consequent
      imbalance are implicated in the pathophysiology of schizophrenia. Reduced GABA
      production would lead to a disinhibition of glutamatergic neurons and
      subsequently cause a disruption of the modulation between GABAergic interneurons
      and glutamatergic neurons. In this study, levels of GABA, Glx (summation of
      glutamate and glutamine), and other metabolites in the anterior cingulate cortex
      were measured and compared between first-episode schizophrenia subjects and
      healthy controls (HC). Diagnostic potential of GABA and Glx as upstream
      biomarkers for schizophrenia was explored. METHODS: Nineteen first-episode
      schizophrenia subjects and fourteen HC participated in this study. Severity of
      clinical symptoms of patients was measured with Positive and Negative Syndrome
      Scale (PANSS). Metabolites were measured using proton magnetic resonance
      spectroscopy, and quantified using internal water as reference. RESULTS: First
      episode schizophrenia subjects revealed reduced GABA and myo-inositol (mI), and
      increased Glx and choline (Cho), compared to HC. No significant correlation was
      found between metabolite levels and PANSS scores. Receiver operator
      characteristics analyses showed Glx had higher sensitivity and specificity
      (84.2%, 92.9%) compared to GABA (73.7%, 64.3%) for differentiating schizophrenia
      patients from HC. Combined model of both GABA and Glx revealed the best
      sensitivity and specificity (89.5%, 100%). CONCLUSION: This study simultaneously
      showed reduction in GABA and elevation in Glx in first-episode schizophrenia
      subjects, and this might provide insights on explaining the disruption of
      modulation between GABAergic interneurons and glutamatergic neurons. Elevated Cho
      might indicate increased membrane turnover; whereas reduced mI might reflect
      dysfunction of the signal transduction pathway. In vivo Glx and GABA revealed
      their diagnostic potential for schizophrenia.

PMID- 28751131
TI  - Recommendations of the Brazilian Society of Rheumatology for diagnosis and
      treatment of Chikungunya fever. Part 1 - Diagnosis and special situations.
AB  - Chikungunya fever has become a relevant public health problem in countries where
      epidemics occur. Until 2013, only imported cases occurred in the Americas, but in
      October of that year, the first cases were reported in Saint Marin island in the
      Caribbean. The first autochthonous cases were confirmed in Brazil in September
      2014; until epidemiological week 37 of 2016, 236,287 probable cases of infection
      with Chikungunya virus had been registered, 116,523 of which had serological
      confirmation. Environmental changes caused by humans, disorderly urban growth and
      an ever-increasing number of international travelers were described as the
      factors responsible for the emergence of large-scale epidemics. Clinically
      characterized by fever and joint pain in the acute stage, approximately half of
      patients progress to the chronic stage (beyond 3 months), which is accompanied by
      persistent and disabling pain. The aim of the present study was to formulate
      recommendations for the diagnosis and treatment of Chikungunya fever in Brazil. A
      literature review was performed in the MEDLINE, SciELO and PubMed databases to
      ground the decisions for recommendations. The degree of concordance among experts
      was established through the Delphi method, involving 2 in-person meetings and
      several online voting rounds. In total, 25 recommendations were formulated and
      divided into 3 thematic groups: (1) clinical, laboratory and imaging diagnosis;
      (2) special situations; and (3) treatment. The first 2 themes are presented in
      part 1, and treatment is presented in part 2.

PMID- 28751132
TI  - Spontaneous Lung Hernia Secondary to Persistent Cough: A Rare Entity.

PMID- 28751133
TI  - Effect of cleaning status on accuracy and precision of oxygen flowmeters of
      various ages.
AB  - OBJECTIVE: To evaluate oxygen flowmeters for accuracy and precision, assess the
      effects of cleaning and assess conformity to the American Society for Testing
      Materials (ASTM) standards. STUDY DESIGN: Experimental study. METHODS: The flow
      of oxygen flowmeters from 31 anesthesia machines aged 1-45 years was measured
      before and after cleaning using a volumetric flow analyzer set at 0.5, 1.0, 2.0,
      3.0, and 4.0 L minute-1. A general linear mixed models approach was used to
      assess flow accuracy and precision. RESULTS: Flowmeters 1 year of age delivered
      accurate mean oxygen flows at all settings regardless of cleaning status.
      Flowmeters >=5 years of age underdelivered at flows of 3.0 and 4.0 L minute-1.
      Flowmeters >=12 years underdelivered at flows of 2.0, 3.0 and 4.0 L minute-1
      prior to cleaning. There was no evidence of any beneficial effect of cleaning on
      accuracy of flowmeters 5-12 years of age (p > 0.22), but the accuracy of
      flowmeters >=15 years of age was improved by cleaning (p < 0.05). Regardless of
      age, cleaning increased precision, decreasing flow variability by approximately
      17%. Nine of 31 uncleaned flowmeters did not meet ASTM standards. After cleaning,
      a different set of nine flowmeters did not meet standards, including three that
      had met standards prior to cleaning. CONCLUSIONS: Older flowmeters were more
      likely to underdeliver oxygen, especially at higher flows. Regardless of age,
      cleaning decreased flow variability, improving precision. However, flowmeters
      still may fail to meet ASTM standards, regardless of cleaning status. CLINICAL
      RELEVANCE: Cleaning anesthesia machine oxygen flowmeters improved precision for
      all tested machines and partially corrected inaccuracies in flowmeters >=15 years
      old. A notable proportion of flowmeters did not meet ASTM standards. Cleaning did
      not ensure that they subsequently conformed to ASTM standards. We recommend
      annual flow output validation to identify whether flowmeters are acceptable for
      continued clinical use.

PMID- 28751134
TI  - Long non-coding RNAs in thyroid cancer: Biological functions and clinical
      significance.
AB  - Thyroid cancer is the most common endocrine malignant tumor with rapidly
      increasing incidence in recent decades. Although the majority of thyroid cancers
      are relatively indolent, some cases still have a risk of developing into more
      aggressive and lethal forms of thyroid cancers. Similar to other malignancies,
      thyroid tumorigenesis is a multistep process involving the accumulation of a
      large number of genetic and epigenetic alterations. Thus, determination of the
      mechanisms of tumorigenesis is an urgent need for thyroid cancer treatment. Long
      noncoding RNAs (LncRNAs) have recently been demonstrated to participate in cancer
      progression. However, their role and molecular mechanism in thyroid cancer remain
      largely unclear. In this review, we focus on the dysregulation of lncRNAs in
      thyroid cancer, summarize the latest findings regarding the functions and
      mechanism of lncRNAs in thyroid cancer, and discuss their potential clinical
      significance in diagnosis and prognosis of thyroid cancer.

PMID- 28751135
TI  - Chronic Sorrow in Parents of Children with a Chronic Illness or Disability: An
      Integrative Literature Review.
AB  - PROBLEM: This integrative review aims to synthesize the findings of studies on
      chronic sorrow in parents, to analyze the findings along three specific research
      questions, and to identify areas for future research. ELIGIBILITY CRITERIA:
      Studies of parents, mothers and/or fathers of non-adult children published in
      peer-reviewed journals that answered the research questions: 1) How does the
      experience of chronic sorrow differ between mothers and fathers? 2) What factors
      have been identified to impact the experience of chronic sorrow over time? 3)
      What strategies by health care providers for helping parents cope with chronic
      sorrow have been identified to be most and least helpful? SAMPLE: Nineteen
      studies from a literature search within the databases of CINAHL, MEDLINE,
      PsycINFO, Psycarticles and SocIndex were included in the review. RESULTS:
      Findings suggest that mothers experience more intense chronic sorrow compared
      with fathers. Health care crises and developmental milestones are potent triggers
      for resurgence of chronic sorrow. Helpful strategies by healthcare providers
      include providing information, helping to procure respite and being empathetic
      and compassionate. CONCLUSIONS: Healthcare providers need to understand that
      chronic sorrow is a normal consequence of having a child with a chronic illness
      or disability. IMPLICATIONS: Family-centered interventions should be
      individualized and aimed at providing increased comfort to parents in times of
      need. Further research that looks at the effectiveness of interventions is
      needed.

PMID- 28751136
TI  - Effects of Covering the Eyes versus Playing Intrauterine Sounds on Premature
      Infants' Pain and Physiological Parameters during Venipuncture.
AB  - BACKGROUND: There is a need to assess the impact of initiatives to reduce
      exposure to environmental light and sound in preterm infants undergoing painful
      interventions in neonatal intensive care units. OBJECTIVES: In this study, we
      aimed to identify the effect of covering the eyes and playing the intrauterine
      ambient sounds on premature infants' pain and physiological parameters during
      venipuncture. METHODS: This was a randomized controlled trial. Ninety-four
      preterm infants were randomly divided into three groups: intrauterine sounds
      (n=32), covered eyes (n=32), and control (n=30) groups. Data were collected on
      the Preterm Infant Information Form, Preterm Infant Follow-up Form, and Neonatal
      Infant Pain Scale (NIPS), used to assess pain. RESULTS: A significant difference
      was found between the intervention and control groups' NIPS score after
      venipuncture, which was primarily due to covered eyes' group. No significant
      difference was found between the intervention and control groups' NIPS score
      during venipuncture. In addition, no significant difference was found between the
      intervention and control groups of infants physiological parameters before,
      during, and after venipuncture. The practice of covering preterm infants' eyes
      during venipuncture positively affected their pain scores after venipuncture.
      CLINICAL IMPLICATIONS: The effect of covering the eyes and playing the
      intrauterine ambient sounds in preterm infants may be recommended as simple,
      safe, and supportive stimuli that facilitate positive effects during painful
      procedures.

PMID- 28751137
TI  - Impact of Non-medical Out-of-pocket Expenses on Families of Children With
      Cerebral Palsy Following Orthopaedic Surgery.
AB  - PURPOSE: Limited research has been conducted on the non-medical out-of-pocket
      expenses (NOOPEs) incurred by families of children with chronic health
      conditions. The study objectives were to: 1) calculate the estimated NOOPEs
      incurred by families during hospitalization of their child, 2) identify
      predictors of high NOOPEs, and 3) assess the impact of the child's chronic health
      condition on the family's finances. DESIGN AND METHODS: Prospective observational
      study. Parents were included if their child was 3-20years old, had severe, non
      ambulatory cerebral palsy (CP), and scheduled for hip or spine surgery. Parents
      reported all NOOPEs incurred during their child's hospitalization using the
      Family Expense Diary. Families completed the subscales of the Impact on Family
      Scale and the Assessment of Caregivers Experience with Neuromuscular Disease.
      Descriptive and univariate and multiple hierarchical regression models were used
      in the analysis. RESULTS: Fifty two parents participated. The total NOOPEs ranged
      from $193.00 to $7192.71 (M=$2001.92) per hospitalization representing an average
      of 4% of the family's annual earned income. Caregiver age (F=8.393, p<0.001),
      income (F=7.535, p<0.001), and distance traveled to the hospital (F=4.497,
      p=0.039) were significant predictors of high NOOPEs. The subscale scores
      indicated that a child's chronic health condition had a significant impact on
      family finances. CONCLUSIONS AND PRACTICE IMPLICATIONS: Hospitalization is
      associated with numerous NOOPEs that create additional financial demands for
      families caring for a child with severe CP. NOOPEs should be addressed when
      preparing families for their children's planned hospital admissions, especially
      those families of CSHCN who experience significant financial impacts secondary to
      their children's care.

PMID- 28751138
TI  - Prognostic Factors of Hearing Outcome in Untreated Vestibular Schwannomas:
      Implication of Subdivision of Their Growth by Volumetric Analysis.
AB  - BACKGROUND: Conservative wait-and-scan management for vestibular schwannomas
      (VSs) is an important treatment option, but its role is unclear because of
      discordance between tumor growth and hearing outcomes. METHODS: The present study
      was a retrospective analysis of 97 patients with sporadic VSs without treatment
      who were followed-up between 2003 and 2012. Tumor volume was measured by 3
      dimensional volumetry at each follow-up visit. The median follow-up duration was
      47 months (range, 13-122 months). The relationship between the tumor growth rate
      and hearing outcome was compared according to stratification of the initial tumor
      volumes. RESULTS: Hearing impairment was related significantly to the initial
      hearing status (Gardner-Robertson grade >=2), initial tumor volume (>=0.1 cm3),
      and tumor growth (>=0.10 cm3/year). During 4 years of follow-up, 26% and 42% of
      the patients with untreated VS showed rapid tumor growth and hearing impairment,
      respectively. For tumors with an initial volume of 0.1-3.0 cm3, hearing
      impairment during the conservative management period was inversely proportional
      to the tumor volume. CONCLUSIONS: Conservative management could be especially
      valid for small (<0.10 cm3), noncystic VSs in patients with Gardner-Robertson
      grade 1 at diagnosis. However, for tumors with a small-to-medium initial volume
      (0.10-3.0 cm3), future hearing impairment might be inversely proportional to
      tumor growth rate. Therefore, small-to-medium sized tumors should be followed-up
      more closely regardless of the initial hearing impairment.

PMID- 28751139
TI  - Identification of Driver Genes and Key Pathways of Pediatric Brain Tumors and
      Comparison of Molecular Pathogenesis Based on Pathologic Types.
AB  - OBJECTIVE: This study is to identify pediatric brain tumors (PBT) driver genes
      and key pathways to detect the expression of the driver genes and also to clarify
      the relationship between patients' prognosis and expression of driver genes.
      METHODS: The gene expression profile of GSE50161 was analyzed to identify the
      differentially expressed genes (DEGs) between tumor tissue and the normal tissue.
      Gene ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein
      protein interaction network analysis were conducted to identify the enrichment
      functions, pathways, and hub genes. After hub genes were identified, quantitative
      reverse transcription polymerase chain reaction was used to confirm the
      differential expression of these hub genes. Survival data of 325 patients' were
      analyzed to clarify the relationship between prognosis and expression levels of
      the mutual hub genes. RESULTS: Gene ontology and Kyoto Encyclopedia of Genes and
      Genomes analysis showed that there were 13 common functions and 3 common pathways
      which were upregulated or downregulated among the 4 groups. Mutual hub genes were
      somatostatin (SST), glutamate decarboxylase 2 (GAD2), and single copy human
      parvalbumin gene (PVALB). The expression of SST, GAD2, and PVALB in glioma cells
      significantly decreased compared with normal glial cells (P < 0.05). In addition,
      survival analysis showed a favorable progression-free and overall survival in
      patients with glioma with SST, GAD2, and PVALB high expression (P < 0.05).
      CONCLUSIONS: SST, GAD2, and PVALB significantly decrease in glioma cells compared
      with normal glial cells. Survival analysis suggests that patients with high
      expressed SST, GAD2, and PVALB have a longer overall and progression-free
      survival. The differential expressed genes identified in this study provide novel
      targets for diagnosis and treatment.

PMID- 28751140
TI  - Lumbosacral Transitional Vertebra: Possible Role in the Pathogenesis of
      Adolescent Lumbar Disc Herniation.
AB  - OBJECTIVE: To investigate the role of lumbosacral transitional vertebra (LSTV) in
      the pathogenesis of adolescent lumbar disc herniation (ALDH) and the association
      between LSTV type and the herniation level of ALDH. METHODS: This study was a
      retrospective case-control analysis of roentgenographic images. All adolescent
      patients who received surgical treatment for L4/5 or L5/S1 single level lumbar
      disc herniation in our department from 2010 to 2015 were eligible for the ALDH
      group. All adolescent patients admitted to our hospital during the same period
      and who had ever undergone a plain anteroposterior radiologic examination of the
      abdomen and met the inclusion criteria that ensured the absence of any spinal
      disorders were selected into the control group. The anteroposterior lumbar or
      abdomen roentgenograms were collected to identify the LSTV. The incidence of LSTV
      in the ALDH group and the control group were compared. Among the ALDH group, the
      association between LSTV type (sacralization or lumbarization) and the herniation
      level of ALDH were evaluated. RESULTS: A total of 80 adolescent patients were
      included in the ALDH group and 92 asymptomatic adolescents were included in the
      control group. LSTV was found in 24 patients (30%) in ALDH group compared with 7
      patients (7.6%) in the control group (P < 0.001; odds ratio, 5.2; 95% confidence
      interval 2.1, 12.9). Among the adolescent patients with sacralization, the L4/5
      disc herniation was significantly more common than L5/S1 (81.3% vs. 18.7%; P =
      0.019). CONCLUSIONS: The LSTV is associated with LDH in adolescents and the
      sacralization of L5 may contribute to the L4/5 disc herniation in adolescent
      patients.

PMID- 28751141
TI  - Histology-Stratified Tumor Control and Patient Survival After Stereotactic
      Radiosurgery for Pineal Region Tumors: A Report From the International Gamma
      Knife Research Foundation.
AB  - BACKGROUND: Pineal region tumors represent a rare and histologically diverse
      group of lesions. Few studies are available to guide management and the outcomes
      after stereotactic radiosurgery (SRS). METHODS: Patients who underwent SRS for a
      pineal region tumor and for whom at least 6 months of imaging follow-up was
      available were retrospectively assessed in 5 centers. Data were collected from
      the medical record and histology level analyses were performed, including
      actuarial tumor control and survival analyses. RESULTS: A total of 70 patients
      were treated between 1989 and 2014 with a median follow-up of 47 months.
      Diagnoses were pineocytoma (37%), pineoblastoma (19%), pineal parenchymal tumor
      of intermediate differentiation (10%), papillary tumor of the pineal region (9%),
      germinoma (7%), teratoma (3%), embryonal carcinoma (1%), and unknown (14%).
      Median prescription dose was 15 Gy at the 50% isodose line. Actuarial local
      control and survival rates were 81% and 76% at 20 years for pineocytoma, 50% and
      56% at 5 years for pineal parenchymal tumor of intermediate differentiation, 27%
      and 48% at 5 years for pineoblastoma, 33% and 100% at 5 years for papillary tumor
      of the pineal region, 80% and 80% at 20 years for germinoma, and 61% and 67% at 5
      years for tumors of unknown histology. New focal neurological deficit, Parinaud
      syndrome, and hydrocephalus occurred in 9%, 7%, and 3% of cases, respectively.
      CONCLUSIONS: SRS is a safe modality for the management of pineal region tumors.
      Its specific role is highly dependent on tumor histology. As such, all efforts
      should be made to obtain a reliable histologic diagnosis.

PMID- 28751142
TI  - Design, synthesis and biological evaluation of dual acetylcholinesterase and
      phosphodiesterase 5A inhibitors in treatment for Alzheimer's disease.
AB  - With the recent research advances in molecular biology and technology, multiple
      credible hypotheses about the progress of Alzheimer's disease (AD) have been
      proposed; multi-target drugs have emerged as an innovative therapeutic approach
      for AD. Current clinical therapy for AD patients is mainly palliative treatment
      targeting acetylcholinesterase (AChE). Inhibition of phosphodiesterase 5A (PDE5A)
      has recently been validated as a potentially novel therapeutic approach for
      Alzheimer's disease (AD). In this work, series of new compounds were designed,
      synthesized and evaluated as dual cholinesterase and PDE5A inhibitor. Biological
      results revealed that some of these compounds display good biological activities
      against AChE with IC50 values about 44.67-169.80nM (donepezil IC50 50.12nM).
      Notably, compound 12 presented potent activities against PDE5A with IC50 values
      about 50MUM (sildenafil IC50 12.59MUM), and some of these compounds showed low
      cell toxicity to A549 cells in vitro.

PMID- 28751143
TI  - N-alkyl-[1,1'-biphenyl]-2-sulfonamide derivatives as novel broad spectrum anti
      epileptic drugs with efficacy equivalent to that of sodium valproate.
AB  - In order to develop phenyl sulfonamides as a novel class of anti-epileptic drugs
      (AED) for both general and partial seizure, we initiated in vivo screening of our
      chemical library in the mice MES and sc-PTZ models and found compounds 1 and 2 as
      lead compounds. Optimization of 1 and 2 led to the discovery of compound 21,
      which showed potent anticonvulsant effect in MES, scPTZ and rat amygdala kindling
      models. These findings indicate that compound 21 could be a useful new broad
      spectrum AED like sodium valproate and provide an opportunity to struggle current
      therapy-resistant epilepsy.

PMID- 28751144
TI  - Interplay between H6PDH and 11beta-HSD1 implicated in the pathogenesis of type 2
      diabetes mellitus.
AB  - Extensive studies have been performed on the role of 11beta-hydroxysteroid
      dehydrogenase 1 (11beta-HSD1) in metabolic diseases. Our previous study reported
      glucose could directly regulate hexose-6-phosphate dehydrogenase (H6PDH) and
      11beta-HSD1. Recently, we further investigated the interplay of H6PDH and 11beta
      HSD1 and their roles in hepatic gluconeogenesis and insulin resistance to
      elucidate the importance of H6PDH and 11beta-HSD1 in pathogenesis of type 2
      diabetes mellitus (T2DM). T2DM rats model and H6PDH or 11beta-HSD1 siRNA
      transfected in CBRH-7919 cells were used to explore the effect of H6PDH and
      11beta-HSD1 in T2DM. The results showed that the expression and activity of H6PDH
      and 11beta-HSD1 in livers of diabetic rats were increased, with the expressions
      of PEPCK and G6Pase or liver corticosterone increased apparently. It also showed
      that H6PDH siRNA and 11beta-HSD1 siRNA could inhibit the protein expression and
      enzyme activity by each other. With H6PDH siRNA, the enhancement of
      gluconeogenesis was blocked and insulin resistance stimulated by corticosterone
      was reduced. H6PDH and 11beta-HSD1 might be the effective and prospective targets
      for T2DM and metabolic syndromes, based on the interplay between these two
      enzymes.

PMID- 28751145
TI  - Synthesis, antiviral activity, and molecular docking study of trans-ferulic acid
      derivatives containing acylhydrazone moiety.
AB  - In this study, we report the synthesis and antiviral activity of trans-ferulic
      acid derivatives containing acylhydrazone moiety. Biological tests demonstrated
      that most target compounds showed potent antiviral activity against tobacco
      mosaic virus (TMV). Compound D4 showed remarkable inactivating activity with EC50
      value of 36.59MUg/mL, which was obviously superior to ribavirin (126.05MUg/mL).
      Molecular docking results revealed that compound D4 exhibited the optimal
      combining capacity with five hydrogen bonds to different amino-acid residues of
      TMV coat protein (TMV-CP). Docking results were consistent with the inactivating
      activity of target compounds against TMV.

PMID- 28751146
TI  - Ethnophytotechnology: Harnessing the Power of Ethnobotany with Biotechnology.
AB  - Ethnobotany (the scientific study of traditional plant knowledge) has aided the
      discovery of important medicines. However, as single-molecule drugs or
      synergistic mixtures, these remedies have faced obstacles in production and
      analysis. Now, advances in bioreactor technology, metabolic engineering, and
      analytical instrumentation are improving the production, manipulation, and
      scientific understanding of such remedies.

PMID- 28751147
TI  - Stem Cell Therapies for Reversing Vision Loss.
AB  - Current clinical trials that evaluate human pluripotent stem cell (hPSC)-based
      therapies predominantly target treating macular degeneration of the eyes because
      the eye is an isolated tissue that is naturally weakly immunogenic. Here, we
      discuss current bioengineering approaches and biomaterial usage in combination
      with stem cell therapy for macular degeneration disease treatment. Retinal
      pigment epithelium (RPE) differentiated from hPSCs is typically used in most
      clinical trials for treating patients, whereas bone marrow mononuclear cells
      (BMNCs) or mesenchymal stem cells (MSCs) are intravitreally transplanted,
      undifferentiated, into patient eyes. We also discuss reported negative effects of
      stem cell therapy, such as patients becoming blind following transplantation of
      adipose-derived stem cells, which are increasingly used by 'stem-cell clinics'.

PMID- 28751148
TI  - Vision for navigation: What can we learn from ants?
AB  - The visual systems of all animals are used to provide information that can guide
      behaviour. In some cases insects demonstrate particularly impressive visually
      guided behaviour and then we might reasonably ask how the low-resolution vision
      and limited neural resources of insects are tuned to particular behavioural
      strategies. Such questions are of interest to both biologists and to engineers
      seeking to emulate insect-level performance with lightweight hardware. One
      behaviour that insects share with many animals is the use of learnt visual
      information for navigation. Desert ants, in particular, are expert visual
      navigators. Across their foraging life, ants can learn long idiosyncratic
      foraging routes. What's more, these routes are learnt quickly and the visual cues
      that define them can be implemented for guidance independently of other social or
      personal information. Here we review the style of visual navigation in solitary
      foraging ants and consider the physiological mechanisms that underpin it. Our
      perspective is to consider that robust navigation comes from the optimal
      interaction between behavioural strategy, visual mechanisms and neural hardware.
      We consider each of these in turn, highlighting the value of ant-like mechanisms
      in biomimetic endeavours.

PMID- 28751149
TI  - The effects of vitamin D supplementation on metabolic profiles and liver function
      in patients with non-alcoholic fatty liver disease: A systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: A systematic review and meta-analysis of randomized controlled trials
      (RCTs) was conducted to summarize the evidence on the effect of vitamin D
      supplementation on metabolic profiles in patients with non-alcoholic fatty liver
      disease (NAFLD). METHODS: We systematically searched PubMed, EMBASE and five
      other databases to identify all RCTs investigating the association between
      vitamin D and NAFLD up until 5 October 2016. Seven RCTs with 452 participants
      (227 patients and 225 controls) were included in the meta-analysis. RESULTS: The
      results showed that vitamin D administration had no beneficial effect on fasting
      plasma glucose (FPG) (standardized mean difference [SMD]-0.23; 95% confidence
      interval [CI], -0.88, 0.42), insulin (SMD -1.09; 95% CI, -2.70,0.52) and
      homeostasis model assessment of insulin resistance (HOMA-IR) (SMD -1.89; 95% CI, 
      3.88,0.09). Vitamin D supplementation also had no effect on lipid profiles
      including triglycerides (SMD -0.36; 95% CI, -1.77, 1.04), and total-cholesterol
      (SMD -0.46; 95% CI: -1.3, 0.39), as well as on aspartate transaminase (AST) (SMD 
      0.53; 95% CI, -1.11, 0.05), alanine aminotransferase (ALT) (SMD -0.66; 95% CI, 
      1.43,0.11), and body mass index (BMI) (SMD -0.25; 95% CI, -0.76,0.27).
      CONCLUSIONS: Vitamin D supplementation had no effect on FPG, insulin, HOMA-IR,
      triglycerides, total-, LDL-cholesterol, AST, ALT, and BMI.

PMID- 28751150
TI  - Prevalence of glucose intolerance in rheumatoid arthritis patients at a tertiary
      care centre in Haryana.
AB  - AIMS: Recent studies have shown increasing prevalence of dysglycemia in
      rheumatoid arthritis (RA) patients. The present study was planned to study the
      prevalence of pre-diabetes and diabetes in RA patients from a tertiary care
      centre in Haryana, India. METHODS: 150 diagnosed cases of rheumatoid arthritis
      which were on follow up in Rheumatology clinic from last one year and equal
      number of age, sex matched controls were recruited for the study. FPG, 2h plasma
      glucose level after 75g oral glucose tolerance test and HbA1c were estimated in
      all the subjects. In RA patients c-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), rheumatoid factor (RF) and Anti-cyclic citrullinated
      (Anti CCP) antibodies were also measured and disease activity was assessed by
      using (DAS28 joint counts) and CDAI. RESULTS: Patients with RA had statistically
      significant higher waist circumference, hip circumference and BMI as compared to
      control group. Prevalence of glucose intolerance in RA patients and control group
      was 14.67% and 6.67% respectively which was statistically significant (p=0.025).
      The prevalence of pre-diabetes was in RA group was not significant statistically.
      There was higher disease activity in glucose intolerant (GI) RA cases as compared
      to normal glucose tolerant (NGT) RA cases. The most commonly used drug
      combination among RA patients was MTX+HCQ+SAAZ (49 patients, 32.67%). Maximum
      glucose intolerance was observed in patients who were on Non-HCQ drug
      combinations. CONCLUSIONS: There is elevated prevalence of glucose intolerance
      among RA patients that is related to high disease activity, visceral adiposity
      and drugs usage.

PMID- 28751151
TI  - Development of Refractive Errors-What Can We Learn From Inherited Retinal
      Dystrophies?
AB  - PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera
      signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are
      characterized by dysfunction of a single retinal cell type and have a high risk
      of refractive errors, a study investigating the affected cell type, causal gene,
      and refractive error in IRDs may provide insight herein. DESIGN: Case-control
      study. METHODS: Study Population: Total of 302 patients with IRD from 2
      ophthalmogenetic centers in the Netherlands. Reference Population: Population
      based Rotterdam Study-III and Erasmus Rucphen Family Study (N = 5550).
      Distributions and mean spherical equivalent (SE) were calculated for main
      affected cell type and causal gene; and risks of myopia and hyperopia were
      evaluated using logistic regression. RESULTS: Bipolar cell-related dystrophies
      were associated with the highest risk of SE high myopia 239.7; odds ratio (OR)
      mild hyperopia 263.2, both P < .0001; SE -6.86 diopters (D) (standard deviation
      [SD] 6.38), followed by cone-dominated dystrophies (OR high myopia 19.5, P <
      .0001; OR high hyperopia 10.7, P = .033; SE -3.10 D [SD 4.49]); rod dominated
      dystrophies (OR high myopia 10.1, P < .0001; OR high hyperopia 9.7, P = .001; SE 
      2.27 D [SD 4.65]), and retinal pigment epithelium (RPE)-related dystrophies (OR
      low myopia 2.7; P = .001; OR high hyperopia 5.8; P = .025; SE -0.10 D [SD 3.09]).
      Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10])
      coincided with the highest degree of myopia and in CABP4 (SE 4.81 D [SD 0.35])
      with the highest degree of hyperopia. CONCLUSIONS: Refractive errors, in
      particular myopia, are common in IRD. The bipolar synapse and the inner and outer
      segments of the photoreceptor may serve as critical sites for myopia development.

PMID- 28751152
TI  - Human umbilical cord blood-derived mesenchymal stromal cells and small intestinal
      submucosa hydrogel composite promotes combined radiation-wound healing of mice.
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are a promising agent for
      treating impaired wound healing, and their therapeutic potential may be enhanced
      by employing extracellular matrix scaffolds as cell culture scaffolds or
      transplant cell carriers. Here, we evaluated the effect of human umbilical cord
      blood-derived (hUCB)-MSCs and a porcine small intestinal submucosa (SIS)-derived
      extracellular matrix scaffold in a combined radiation-wound mouse model of
      impaired wound healing. METHODS: hUCB-MSCs and SIS hydrogel composite was applied
      to the excisional wound of whole-body irradiated mice. Assessment of wound
      closing and histological evaluation were performed in vivo. We also cultured hUCB
      MSCs on SIS gel and examined the angiogenic effect of conditioned medium on
      irradiated human umbilical vein endothelial cells (HUVECs) in vitro. RESULTS:
      hUCB-MSCs and SIS hydrogel composite treatment enhanced wound healing and
      angiogenesis in the wound site of mice. Conditioned medium from hUCB-MSCs
      cultured on SIS hydrogel promoted the chemotaxis of irradiated HUVECs more than
      their proliferation. The secretion of angiogenic growth factors hepatocyte growth
      factor, vascular endothelial growth factor-A and angiopoietin-1 from hUCB-MSCs
      was significantly increased by SIS hydrogel, with HGF being the predominant
      angiogenic factor of irradiated HUVECs. CONCLUSIONS: Our results suggest that the
      wound healing effect of hUCB-MSCs is enhanced by SIS hydrogel via a paracrine
      factor-mediated recruitment of vascular endothelial cells in a combined radiation
      wound mouse model.

PMID- 28751153
TI  - CCR5-edited gene therapies for HIV cure: Closing the door to viral entry.
AB  - Human immunodeficiency virus (HIV) was first reported and characterized more than
      three decades ago. Once thought of as a death sentence, HIV infection has become
      a chronically manageable disease. However, it is estimated that a staggering 0.8%
      of the world's population is infected with HIV, with more than 1 million deaths
      reported in 2015 alone. Despite the development of effective anti-retroviral
      drugs, a permanent cure has only been documented in one patient to date. In 2007,
      an HIV-positive patient received a bone marrow transplant to treat his leukemia
      from an individual who was homozygous for a mutation in the CCR5 gene. This
      mutation, known as CCR5Delta32, prevents HIV replication by inhibiting the early
      stage of viral entry into cells, resulting in resistance to infection from the
      majority of HIV isolates. More than 10 years after his last dose of anti
      retroviral therapy, the transplant recipient remains free of replication
      competent virus. Multiple groups are now attempting to replicate this success
      through the use of other CCR5-negative donor cell sources. Additionally,
      developments in the use of lentiviral vectors and targeted nucleases have opened
      the doors of precision medicine and enabled new treatment methodologies to combat
      HIV infection through targeted ablation or down-regulation of CCR5 expression.
      Here, we review historical cases of CCR5-edited cell-based therapies, current
      clinical trials and future benefits and challenges associated with this
      technology.

PMID- 28751154
TI  - The etiology and bacteriology of healthcare-associated empyema are quite
      different from those of community-acquired empyema.
AB  - OBJECTS: Changes in patients' background and life environment could contribute to
      increase healthcare-associated (HCA) empyema. There are no guidelines and
      statements for HCA empyema. METHODS: We retrospectively reviewed all patients
      with empyema who were admitted to the Aichi Medical University Hospital, Japan
      between 2008 and 2015. We evaluated patients' characteristics, microbial
      profiles, treatment and outcomes, and analyzed prognostic factors for 90-day
      mortality. RESULTS: A total of 48 patients were enrolled in this study. They were
      categorized into community-acquired (CA) empyema (16 patients) and healthcare
      associated (HCA) empyema (32 patients). HCA empyema patients had higher Charlson
      comorbidity index (CCI) scores, and poorer performance status (PS) than CA
      empyema patients. Potentially-drug resistant (PDR) pathogens were seen more
      frequently in HCA empyema than in CA empyema. Compared with survival and death
      groups, the death group showed higher CCI scores and poorer PSs than the survival
      group. The death group had more malignancy than the survival group. PDR pathogens
      were detected more frequently in the death group than in the survival group.
      Multivariate analysis showed that emergence of PDR pathogens and malignancies
      were independent poor prognostic factors for 90-days mortality among empyema.
      CONCLUSION: The etiology and bacteriology of HCA empyema are quite different from
      those of CA empyema. Especially, the mortality of HCA empyema was higher than the
      one of CA empyema. Emergence of PDR pathogens in the pleural fluid detected by
      culture, pulmonary disease and malignancies were independent poor prognostic
      factors among CA and HCA empyema by multivariate logistic regression analysis.

PMID- 28751155
TI  - Primary lung abscess caused by Staphylococcus lugdunensis.
AB  - Staphylococcus lugdunensis, a strain of coagulase-negative staphylococci, is part
      of the normal flora of human skin but can cause multiple infections at various
      sites. This microorganism has emerged as a major human pathogen. However, no
      study has reported primary lung abscess caused by S. lugdunensis. A 54-year-old
      alcoholic man without relevant past medical history was admitted because of
      primary lung abscesses. Empirical amoxicillin/clavulanate therapy was initially
      administered; however, the patient had persistent pleuritic chest pain and fever.
      He subsequently underwent resection of the lung abscess and removal of exudative
      pleural effusion on the fourth hospital day. Histopathologic examination
      confirmed the diagnosis of lung abscess, and colonies of gram-positive bacteria
      were identified. The culture specimen from the abscess was positive for S.
      lugdunensis, which was susceptible to amoxicillin/clavulanate, cefazolin,
      ciprofloxacin, clindamycin, erythromycin, oxacillin, teicoplanin, tetracycline,
      and vancomycin. Following resection and 3 weeks of amoxicillin/clavulanate
      therapy, the patient eventually recovered well without relapse. This case report
      is the first to describe S. lugdunensis as a cause of primary lung abscess; this
      microorganism should be considered a potential monomicrobial pathogen in primary
      lung abscess.

PMID- 28751156
TI  - Performance evaluation of the Verigene(r)Clostridium difficile nucleic acid test,
      an automated multiplex molecular testing system for detection of C. difficile
      toxin.
AB  - The Verigene(r)Clostridium difficile nucleic acid test (Verigene(r) CDF test) is
      an automatic and rapid detection system for the genes encoding tcdA, tcdB, binary
      toxin, and the single nucleotide deletion at base pair 117 in the tcdC based on
      microarray and PCR amplification. We compared the performance of the Verigene(r)
      CDF test to that of two enzyme immunoassays, C. DIFF QUIK CHEK COMPLETE and
      X/Pect Toxin A/B, using 118 specimens. We found overall concordance rates of
      81.4% and 78.8% between C. DIFF QUIK CHEK COMPLETE and Verigene(r) CDF test, and
      X/Pect Toxin A/B and Verigene(r) CDF test. The Verigene(r) CDF test showed the
      highest sensitivity (93.9%) and had a specificity of 96.5%. The sensitivity and
      specificity were respectively 45.5 and 94.1% for C. DIFF QUIK CHEK COMPLETE and
      27.3 and 100.0% for X/Pect Toxin A/B. These results indicated that the
      Verigene(r) CDF test was highly accurate for the detection of C. difficile toxin
      in fecal specimens and supported its use in daily diagnostic practice.

PMID- 28751157
TI  - End-of-Life Decision Making for Parents of Extremely Preterm Infants.
AB  - OBJECTIVE: To explore parental attitudes and values in the end-of-life decision
      making process of extremely preterm infants (gestational age < 28 weeks). DESIGN:
      Hermeneutically oriented qualitative research design with in-depth interviews.
      SETTING: Level III NICU in Switzerland. PARTICIPANTS: Purposive sample of seven
      couples, five mothers, and one father (20 parents). METHODS: Qualitative content
      analysis was used to categorize and interpret themes from parents' narratives.
      RESULTS: Parents described factors that affected the decision-making process in
      satisfactory or unsatisfactory ways. Transparent information, empathy, and
      honesty enhanced communication between parents and the health care team. Lack of
      transparent information and continuous support decreased satisfaction. The level
      of involvement in decisions differed by setting. Most parents made decisions
      regarding lung maturation and/or initiation of care in the delivery room. Parent
      participation in the NICU was experienced differently. Contrary to the hospital's
      ethical model, few parents recalled being involved in the decision-making
      process. Some parents experienced a dissociative state of mind that hindered
      their involvement, whereas others felt actively involved. CONCLUSIONS: Our
      results suggest the need for careful and continuous professional evaluation of
      parents' wishes about involvement in the decision-making process, along with
      descriptions of medical facts and treatment options. A lack of attentive
      listening and dialogue may cause paternalistic decision trajectories.

PMID- 28751158
TI  - Mentors Offering Maternal Support Reduces Prenatal, Pregnancy-Specific Anxiety in
      a Sample of Military Women.
AB  - OBJECTIVE: To determine the efficacy of the Mentors Offering Maternal Support
      (MOMS) program to reduce pregnancy-specific anxiety and depression and build self
      esteem and resilience in military women. DESIGN: Randomized controlled trial with
      repeated measures. SETTING: Large military community in Texas. PARTICIPANTS:
      Pregnant women (N = 246) in a military sample defined as active duty or spouse of
      military personnel. METHODS: Participants were randomized in the first trimester
      to the MOMS program or normal prenatal care. Participants attended eight 1-hour
      sessions every other week during the first, second, and third trimesters of
      pregnancy. Pregnancy-specific anxiety, depression, self-esteem, and resilience
      were measured in each trimester. Linear mixed models were used to compare the two
      group difference in slope for prenatal anxiety, depression, self-esteem, and
      resilience. RESULTS: The Prenatal Self-Evaluation Questionnaire was used to
      measure perinatal anxiety. Rates of prenatal anxiety on the Identification With a
      Motherhood Role (p = .049) scale and the Preparation for Labor (p = .017) scale
      were significantly reduced for participants in MOMS. Nulliparous participants
      showed significantly lower anxiety on the Acceptance of Pregnancy scale and
      significantly greater anxiety on the Preparation for Labor scale. Single
      participants had significantly greater anxiety on the Well-Being of Self and Baby
      in Labor scale, and participants with deployed husbands had significantly greater
      anxiety on the Identification With a Motherhood Role scale. CONCLUSION:
      Participation in the MOMS program reduced pregnancy-specific prenatal anxiety for
      the dimensions of Identification With a Motherhood Role and Preparation for
      Labor. Both dimensions of anxiety were previously found to be significantly
      associated with preterm birth and low birth weight. Military leaders have
      recognized the urgent need to support military families.

PMID- 28751159
TI  - Ghrelin ameliorates acute lung injury induced by oleic acid via inhibition of
      endoplasmic reticulum stress.
AB  - AIMS: Acute lung injury (ALI) is associated with excessive mortality and lacks
      appropriate therapy. Ghrelin is a novel peptide that protects the lung against
      ALI. This study aimed to investigate whether endoplasmic reticulum stress (ERS)
      mediates the protective effect of ghrelin on ALI. MAIN METHODS: We used a rat
      oleic acid (OA)-induced ALI model. Pulmonary impairment was detected by
      hematoxylin and eosin (HE) staining, lung mechanics, wet/dry weight ratio, and
      arterial blood gas analysis. Plasma and lung content of ghrelin was examined by
      ELISA, and mRNA expression was measured by quantitative real-time PCR. Protein
      levels were detected by western blot. KEY FINDINGS: Rats with OA treatment showed
      significant pulmonary injury, edema, inflammatory cellular infiltration, cytokine
      release, hypoxia and CO2 retention as compared with controls. Plasma and
      pulmonary content of ghrelin was reduced in rats with ALI, and mRNA expression
      was downregulated. Ghrelin (10nmol/kg) treatment ameliorated the above symptoms,
      but treatment with the ghrelin antagonists D-Lys3 GHRP-6 (1MUmol/kg) and JMV 2959
      (6mg/kg) exacerbated the symptoms. ERS induced by OA was prevented by ghrelin and
      augmented by ghrelin antagonist treatment. The ERS inducer, tunicamycin (Tm)
      prevented the ameliorative effect of ghrelin on ALI. The decreased ratio of p-Akt
      and Akt induced by OA was improved by ghrelin treatment, and was further
      exacerbated by ghrelin antagonists. SIGNIFICANCE: Ghrelin protects against ALI by
      inhibiting ERS. These results provide a new target for prevention and therapy of
      ALI.

PMID- 28751160
TI  - M4IDP, a zoledronic acid derivative, induces G1 arrest, apoptosis and autophagy
      in HCT116 colon carcinoma cells via blocking PI3K/Akt/mTOR pathway.
AB  - AIMS: The aim of this work was to examine the antitumor effects and mechanisms of
      M4IDP, a zoledronic acid derivative, on human colorectal cancer (CRC) HCT116
      cells. MAIN METHODS: The effects of M4IDP on proliferation, cell cycle and ROS
      production were determined by CCK-8 and flow cytometry assays. Annexin-V-FITC/PI,
      Hoechst 33258, MDC staining assays and Ad-mCherry-GFP-LC3B fluorescence assay
      were performed to investigate apoptosis and autophagy. The effects of M4IDP on
      the induction of ER stress as well as the expression of cell cycle, apoptosis and
      autophagy-related proteins were analyzed by western blot assay. KEY FINDINGS:
      M4IDP exhibited strong and sustained inhibitory effect on the growth of HCT116
      cells. G1 arrest caused by M4IDP might be attributed to the enhancement of p27
      and reduction of cyclin D1 expression. Proper-time treatment of M4IDP activated
      autophagy and promoted autophagic flux, while long-time treatment might inhibit
      the autophagic degradation and undermine the autophagy. M4IDP-induced apoptosis
      and autophagy were related to the ROS production and subsequent ER stress. M4IDP
      treatment increased the expression of PTEN, inhibited the phosphorylation of
      PDK1, Akt, mTOR, p70S6K, and increased the phosphorylation of GSK-3beta and Bad,
      suggesting that the inhibition of PI3K/Akt/mTOR pathway might be involved in the
      antitumor activities of M4IDP. SIGNIFICANCE: Our study indicates the antitumor
      properties of M4IDP and its potential clinical use in CRC therapy by blocking
      PI3K/Akt/mTOR pathway. This study also provides a better understanding of the
      antitumor effects and the underlying mechanisms of bisphosphonates in the field
      of CRC therapy.

PMID- 28751161
TI  - New perspectives of physiological and pathological functions of nucleolin (NCL).
AB  - Nucleolin (NCL) is a multifunctional protein that mainly localized in the
      nucleolus, it is also found in the nucleoplasm, cytoplasm and cell membrane. The
      three main structural domains allow the interaction of NCL with different
      proteins and RNA sequences. Moreover, specific post-translational modifications
      and its shuttling property also contribute to its multifunctionality. NCL has
      been demonstrated to be involved in a variety of aspects such as ribosome
      biogenesis, chromatin organization and stability, DNA and RNA metabolism,
      cytokinesis, cell proliferation, angiogenesis, apoptosis regulation, stress
      response and microRNA processing. NCL has been increasingly implicated in several
      pathological processes, especially in tumorigenesis and viral infection, which
      makes NCL a potential target for the development of anti-tumor and anti-viral
      strategies. In this review, we present an overview on the structure,
      localizations and various functions of NCL, and further describe how the multiple
      functions of NCL are correlated to its multiple cellular distributions.

PMID- 28751162
TI  - New insights into the factors affecting synonymous codon usage in human infecting
      Plasmodium species.
AB  - Codon usage bias is due to the non-random usage of synonymous codons for coding
      amino acids. The synonymous sites are under weak selection, and codon usage bias
      is maintained by the equilibrium in mutational bias, genetic drift and selection
      pressure. The differential codon usage choices are also relevant to human
      infecting Plasmodium species. Recently, P. knowlesi switches its natural host,
      long-tailed macaques, and starts infecting humans. This review focuses on the
      comparative analysis of codon usage choices among human infecting P. falciparum
      and P. vivax along with P. knowlesi species taking their coding sequence data.
      The variation in GC content, amino acid frequencies, effective number of codons
      and other factors plays a crucial role in determining synonymous codon choices.
      Within species codon choices are more similar for P. vivax and P. knowlesi in
      comparison with P. falciparum species. This study suggests that synonymous codon
      choice modulates the gene expression level, mRNA stability, ribosome speed,
      protein folding, translation efficiency and its accuracy in Plasmodium species,
      and provides a valuable information regarding the codon usage pattern to
      facilitate gene cloning as well as expression and transfection studies for
      malaria causing species.

PMID- 28751163
TI  - Leishmaniasis in the major endemic region of Plurinational State of Bolivia:
      Species identification, phylogeography and drug susceptibility implications.
AB  - The Plurinational State of Bolivia is one of the Latin American countries with
      the highest prevalence of leishmaniasis, highlighting the lowlands of the
      Department of La Paz where about 50% of the total cases were reported. The
      control of the disease can be seriously compromised by the intrinsic variability
      of the circulating species that may limit the efficacy of treatment while
      favoring the emergence of resistance. Fifty-five isolates of Leishmania from
      cutaneous and mucocutaneous lesions from patients living in different provinces
      of the Department of La Paz were tested. Molecular characterization of isolates
      was carried out by 3 classical markers: the rRNA internal transcribed spacer 1
      (ITS-1), the heat shock protein 70 (HSP70) and the mitochondrial cytochrome b
      (Cyt-b). These markers were amplified by PCR and their products digested by the
      restriction endonuclease enzymes AseI and HaeIII followed by subsequent
      sequencing of Cyt-b gene and ITS-1 region for subsequent phylogenetic analysis.
      The combined use of these 3 markers allowed us to assign 36 isolates (65.5%) to
      the complex Leishmania (Viannia) braziliensis, 4 isolates (7, 27%) to L.
      (Viannia) lainsoni. and the remaining 15 isolates (23.7%) to a local variant of
      L. (Leishmania) mexicana. Concerning in vitro drug susceptibility the amastigotes
      from all isolates where highly sensitive to Fungizone(r) (mean IC50 between 0.23
      and 0.5MUg/mL) whereas against Glucantime(r) the sensitivity was moderate (mean
      IC50 ranging from 50.84MUg/mL for L. (V.) braziliensis to 18.23MUg/mL for L. (L.)
      mexicana. L. (V.) lainsoni was not sensitive to Glucantime(r). The susceptibility
      to miltefosine was highly variable among species isolates, being L. (L.) mexicana
      the most sensitive, followed by L. (V.) braziliensis and L. (V.) lainsoni (mean
      IC50 of 8.24MUg/mL, 17.85MUg/mL and 23.28MUg/mL, respectively).

PMID- 28751164
TI  - Coronary Serum Obtained After Myocardial Infarction Induces Angiogenesis and
      Microvascular Obstruction Repair. Role of Hypoxia-inducible Factor-1A.
AB  - INTRODUCTION AND OBJECTIVES: Microvascular obstruction (MVO) exerts deleterious
      effects following acute myocardial infarction (AMI). We investigated coronary
      angiogenesis induced by coronary serum and the role of hypoxia-inducible factor
      1A (HIF-1A) in MVO repair. METHODS: Myocardial infarction was induced in swine by
      transitory 90-minute coronary occlusion. The pigs were divided into a control
      group and 4 AMI groups: no reperfusion, 1minute, 1 week and 1 month after
      reperfusion. Microvascular obstruction and microvessel density were quantified.
      The proangiogenic effect of coronary serum drawn from coronary sinus on
      endothelial cells was evaluated using an in vitro tubulogenesis assay.
      Circulating and myocardial HIF-1A levels and the effect of in vitro blockade of
      HIF-1A was assessed. RESULTS: Compared with control myocardium, microvessel
      density decreased at 90-minute ischemia, and MVO first occurred at 1minute after
      reperfusion. Both peaked at 1 week and almost completely resolved at 1 month.
      Coronary serum exerted a neoangiogenic effect on coronary endothelial cells in
      vitro, peaking at ischemia and 1minute postreperfusion (32 +/- 4 and 41 +/- 9
      tubes vs control: 3 +/- 3 tubes; P < .01). Hypoxia-inducible factor-1A increased
      in serum during ischemia (5-minute ischemia: 273 +/- 52 pg/mL vs control: 148 +/-
      48 pg/mL; P < .01) being present on microvessels of all AMI groups (no
      reperfusion: 67% +/- 5% vs control: 15% +/- 17%; P < .01). In vitro blockade of
      HIF-1A reduced the angiogenic response induced by serum. CONCLUSIONS: Coronary
      serum represents a potent neoangiogenic stimulus even before reperfusion; HIF-1A
      might be crucial. Coronary neoangiogenesis induced by coronary serum can
      contribute to understanding the pathophysiology of AMI.

PMID- 28751165
TI  - Predictors of a Successful Urology Resident Using Medical Student Application
      Materials.
AB  - OBJECTIVE: To evaluate features from the medical student application record that
      predict for a high-quality urology resident because there are currently sparse
      data on factors that are associated with a successful urology residency.
      MATERIALS AND METHODS: We reviewed the Mayo Clinic experience with 53 urology
      residents who matriculated between 2000 and 2011. Residents were independently
      scored 1-10 based on overall quality by the Program Director and Associate
      Program Director. Discrepant scoring by >2 was resolved by the former Program
      Director. Associations of features from the medical student application with an
      excellent score (defined as 8-10) were evaluated with logistic regression.
      RESULTS: Discrepant scoring >2 was noted in only 3 residents (6%). Among the 53
      residents, the mean overall score was 6.2 (standard deviation 3.0, range 1-10)
      and 20 residents (38%) had an excellent score of 8-10. Univariably, higher United
      States Medical Licensing Examination step II score (P = .011), election to Alpha
      Omega Alpha (P = .017), no negative interview comments (P = .044), lower ranked
      medical school (P = .015), honors in obstetrics and gynecology clerkship (P =
      .044), and honors in all core clinical clerkships (P = .007) were significantly
      associated with an excellent score. In a multivariable model, no negative
      interview comments (P = .018), lower ranked medical school (P = .012), and honors
      in all core clinical clerkships (P = .006) were independently associated with an
      excellent score; the c-index for this model was 0.91. CONCLUSION: We demonstrate
      features associated with an excellent urology resident, most notably an honors
      grade in all core clinical clerkships.

PMID- 28751166
TI  - Clinical and demographic characteristics among patients with urothelial
      carcinomas of the upper urinary tract and bladder in Taiwan.
AB  - BACKGROUND: Urothelial carcinoma (UC) is derived from the urothelium of the
      urinary tract, and includes cancers of the bladder, renal pelvis and ureter. The
      aim of this study was to investigate the clinical and demographic features among
      patients with bladder cancer and urothelial carcinoma of the upper urinary tract
      (UTUC) in Taiwan. METHODS: The present study recruited a total of 736
      histopathologically confirmed UC cases, which consisted of 470 bladder cancer and
      266 UTUC between September 1998 and December 2009. Clinical and demographic
      features were collected by an interview utilizing a structured questionnaire, and
      supplemented by medical chart review. This study was approved by institutional
      review boards of the collaborating hospitals. The multivariate Cox proportional
      hazards model was performed to investigate prognostic factors for disease-free
      survival (DFS) and overall survival (OS). All statistical analyses were performed
      using the Statistical Analysis Software for Windows, version 9.1 (SAS Institute,
      Cary, NC, USA). RESULTS: UTUC patients had higher proportions of advanced
      clinical stage (T2-4) and poor cell differentiation (G3). Bladder cancer patients
      with advanced clinical stages (T2-3 and T4) had increased risks of poorer OS
      (hazard ratio, HR = 1.7 and 3.9, respectively). UTUC patients with the advanced
      clinical stage (T4) had a significantly greater risk of poorer OS (HR = 8.7).
      Bladder cancer patients with a high grade (G2-3) had a significantly increased
      risk of poorer OS (HR = 3.8). CONCLUSION: Based on the limited parameters and
      heterogeneous data, the present study merely observed that bladder cancer and
      UTUC patients with the higher tumor stage have a significant increased risk of
      poor overall survival. Therefore, the causal mechanisms of UC prognosis remained
      to be further explored in a larger population.

PMID- 28751167
TI  - Volume-staged gamma knife surgery for the treatment of large skull base
      meningioma surrounding the optical apparatus: A snowman-shape design.
AB  - BACKGROUND: In cases of meningioma surrounding the optical apparatus, this study
      sought to reduce the incidence of radiation-induced optical neuropathy resulting
      from gamma knife surgery (GKS) by dividing the treatment volume into 2 or 3
      fractions. METHODS: Four patients with a large skull base meningioma (1 male and
      3 females; median age: 42 years; range: 33-43 yrs) were treated using volume
      staged GKS. In stage I, the large basal part of the tumor (13.2 mL; range: 3.9
      54.7 mL) was treated with a marginal dose of 13.5 Gy (range: 12-15 Gy). In stage
      II, treatment focused on the smaller upper portion of the tumor located close to
      the optical apparatus (4.3 mL; range: 1.5-16.2 mL), and the marginal dose was 9
      Gy (range: 8-10 Gy). RESULTS: All patients tolerated the treatments well, and
      tumors regressed over a median follow-up period of 100.5 months (range: 42-122
      mos). Specifically, a 34-46% reduction in tumor volume was observed. All four
      patients presented improvements in the neurological deficits observed prior to
      GKS treatment, albeit to varying degrees. No adverse effects of radiation or new
      visual deterioration were observed during the follow-up period. Furthermore, no
      evidence of new endocrine dysfunction or new cranial nerve neuropathy was
      observed within a follow-up period of 100.5 months. CONCLUSION: The application
      of volume-staged GKS using snowman-shape design appears to be an effective
      approach to control tumor growth when treating benign meningiomas surrounding the
      optical apparatus. This approach enables the application of higher radiation
      dosages to facilitate tumor control while still preserving optic nerve function.

PMID- 28751168
TI  - Outcomes of Treatment Strategies for Isolated Spontaneous Dissection of the
      Superior Mesenteric Artery: A Systematic Review.
AB  - BACKGROUND: Isolated spontaneous dissection of the superior mesenteric artery
      (SMA) without aortic dissection is being increasingly recognized. This study
      aimed to evaluate the latest clinical characteristics and optimal treatment.
      METHODS: We searched the Cochrane Library, MEDLINE, and Clinical Trial.gov
      databases through December 31, 2016, using the following words: "superior
      mesenteric artery" and "dissection." We retrieved articles presenting the
      treatment and outcomes of isolated SMA dissection published in English. We
      investigated the patient characteristics, treatments, follow-up, and prognoses.
      Additionally, we compared mortality rates and assessed the need for additional
      interventions between treatment strategies in symptomatic patients without
      accompanying proof of bowel ischemia or aneurysm, which require immediate
      endovascular treatment or surgery. RESULTS: We identified 51 articles with 721
      patients. The initial treatments in symptomatic patients without accompanying
      proof of bowel ischemia or aneurysm were conservative treatment (82.1%),
      endovascular treatment (14.3%), catheter-directed infusion of medication (2.1%),
      and surgery (1.5%). Additional treatment was needed in 18.1% of patients
      receiving conservative treatment and 2.4% of patients receiving endovascular
      treatment (P = 0.0003). Mortality was not significantly different between each
      treatment strategy (P = 0.92). CONCLUSIONS: There was no significant difference
      in mortality of symptomatic SMA dissection patients without accompanying proof of
      bowel ischemia or aneurysm between interventional treatment and conservative
      treatment. An additional treatment is needed in a minority of patients receiving
      conservative treatment, however, more frequently than in those receiving
      endovascular treatment.

PMID- 28751169
TI  - Differences in laser-Doppler indices between skin-surface measurement sites in
      subjects with diabetes.
AB  - This study performed laser-Doppler flowmetry (LDF) measurements with the aim of
      identifying differences in diabetes-induced microcirculatory-blood-flow (MBF)
      responses between the following skin surface measurement sites: an acupoint
      around the wrist, an acupoint around the ankle, and a nearby nonacupoint around
      the ankle. The 67 study subjects were assigned to diabetic, prediabetic, and
      healthy groups according to the results of oral glucose tolerance tests. Beat-to
      beat and spectral analyses were applied to the LDF waveform to obtain the foot
      delay time (FDT), the flow rise time (FRT), and the relative energy contributions
      (RECs) in five frequency bands. FRT and FDT were significantly shorter and the
      RECs of the endothelial-, neural-, and myogenic-related frequency bands were
      significantly smaller in the diabetic group than in the control group at the
      acupoint around the ankle, but there were no such prominent differences at the
      other sites. The acupoint around the ankle was better than the nearby nonacupoint
      and the acupoint around the wrist for distinguishing the age-matched diabetic,
      prediabetic, and healthy subjects. These findings imply that when monitoring
      diabetes-induced MBF responses, the measurement locations should be chosen
      carefully in order to minimize interference effects and to improve the ability to
      distinguish subjects with different conditions.

PMID- 28751170
TI  - Rehabilitation of distal radioulnar joint instability.
AB  - Distal radioulnar joint (DRUJ) instabilities are common and often combined with
      other injuries of the interosseous membrane and/or the proximal radioulnar joint.
      Once they are diagnosed and the treatment is chosen, physiotherapists have
      limited choices due to the lack of validated protocols. The benefits of
      proprioception and neuromuscular rehabilitation have been brought to light for
      the shoulder, knee and ankle joints, among others. However, no program has been
      described for the DRUJ. The purpose of this article is to study the muscular
      elements responsible for active DRUJ stability, and to propose a proprioceptive
      rehabilitation program suited to this condition.

PMID- 28751171
TI  - Use of IFN-gamma and IP-10 detection in the diagnosis of latent tuberculosis
      infection in patients with inflammatory rheumatic diseases.
AB  - OBJECTIVES: Biologic agents are used against rheumatic diseases, however, they
      increase the risk of developing severe infections and diseases such as
      tuberculosis. We aimed to determine the benefits of IP-10 detection to diagnose
      latent tuberculosis infection (LTBI) in patients with inflammatory rheumatic
      diseases on different immunosuppressive drug regimens, and compare these results
      with IFN-gamma detection. MATERIALS AND METHODS: We included 64 patients with
      inflammatory rheumatic diseases. We used QuantiFERON Gold In-Tube (QFN-G-IT) and
      T-SPOT.TB to detect IFN-gamma production, and an in-house ELISA for IP-10
      detection from the previous QFN-G-IT stimulated samples. We assessed the combined
      use of IFN-gamma release assays (IGRAs) and IP-10 test, and analyzed the
      influence of immunotherapy on the tests performance. RESULTS: We obtained 34.9%
      positive results by T-SPOT.TB, 25.0% by QFN-G-IT and 31.3% by IP-10 test. The
      combined use of IGRAs and IP-10 detection increased significantly the amount of
      positive results (p < 0.0001). Treatment intake had no significant effect on in
      vitro tests (p > 0.05). CONCLUSIONS: IP-10 and IFN-gamma detection is comparable
      and their combined use could increase the number of positive results in the
      diagnosis of LTBI in rheumatic patients. The tested assays were not influenced by
      rheumatoid immunosuppressive therapy. Thus, IP-10 could be of use in the
      development of new and improved LTBI diagnostic tools.

PMID- 28751172
TI  - Detection of Lyme disease causing Borrelia burgdorferi s.l. in questing Ixodes
      ricinus ticks on Jersey.

PMID- 28751173
TI  - Identification and recovery of rare-earth permanent magnets from waste electrical
      and electronic equipment.
AB  - Nd-Fe-B permanent magnets are a strategic material for a number of emerging
      technologies. They are a key component in the most energy efficient electric
      motors and generators, thus, they are vital for energy technologies, industrial
      applications and automation, and future forms of mobility. Rare earth elements
      (REEs) such as neodymium, dysprosium and praseodymium are also found in waste
      electrical and electronic equipment (WEEE) in volumes that grow with the
      technological evolution, and are marked as critical elements by the European
      Commission due to their high economic importance combined with significant supply
      risks. Recycling could be a good approach to compensate for the lack of rare
      earths (REs) on the market. However, less than 1% of REs are currently being
      recycled, mainly because of non-existing collection logistics, lack of
      information about the quantity of RE materials available for recycling and
      recycling-unfriendly product designs. To improve these lack of information,
      different waste streams of electrical and electronic equipment from an industrial
      recycling plant were analyzed in order to localize, identify and collect RE
      permanent magnets of the Nd-Fe-B type. This particular type of magnets were
      mainly found in hard disk drives (HDDs) from laptops and desktop computers, as
      well as in loudspeakers from compact products such as flat screen TVs, PC
      screens, and laptops. Since HDDs have been investigated thoroughly by many
      authors, this study focusses on other potential Nd-Fe-B resources in electronic
      waste. The study includes a systematic survey of the chemical composition of the
      Nd-Fe-B magnets found in the selected waste streams, which illustrates the
      evolution of the Nd-Fe-B alloys over the years. The study also provides an
      overview over the types of magnets integrated in different waste electric and
      electronic equipment.

PMID- 28751174
TI  - An equivalent-time-lines model for municipal solid waste based on its compression
      characteristics.
AB  - Municipal solid waste (MSW) demonstrates a noticeable time-dependent stress
      strain behavior, which contributes greatly to the settlement of landfills and
      therefore influences both the storage capacity of landfills and the integrity of
      internal structures. The long-term compression tests for MSW under different
      biodegradation conditions were analyzed. It showed that the primary compression
      can affect the secondary compression due to the biodegradation and mechanical
      creep. Based on the time-lines model for clays and the compression
      characteristics of MSW, relationships between MSW's viscous strain rate and
      equivalent time were established, and then the viscous strain functions of MSW
      under different biodegradation conditions were deduced, and an equivalent-time
      lines model for MSW settlement for two biodegradation conditions was developed,
      including the Type I model for the enhanced biodegradation condition and the Type
      II model for the normal biodegradation condition. The simulated compression
      results of laboratory and field compression tests under different biodegradation
      conditions were consistent with the measured data, which showed the reliability
      of both types of the equivalent-time-lines model for MSW. In addition,
      investigations of the long-term settlement of landfills from the literature
      indicated that the Type I model is suitable for predicting settlement in MSW
      landfills with a distinct biodegradation progress of MSW, a high content of
      organics in MSW, a short fill age or under an enhanced biodegradation
      environment; while the Type II model is good at predicting settlement in MSW
      landfills with a distinct progress of mechanical creep compression, a low content
      of organics in MSW, a long fill age or under a normal biodegradation condition.
      Furthermore, relationships between model parameters and the fill age of landfills
      were summarized. Finally, the similarities and differences between the equivalent
      time-lines model for MSW and the stress-biodegradation model for MSW were
      discussed.

PMID- 28751175
TI  - Benefits to decomposition rates when using digestate as compost co-feedstock:
      Part I - Focus on physicochemical parameters.
AB  - Anaerobic digestion (AD) has gained a significant role in municipal solid waste
      management, but managing a high volume of digestate is one of the challenges with
      AD technology. One option is to mix digestate with fresh and/or stabilized
      organic waste and then feed to the composting process. In this study, the effect
      of co-composting anaerobic digestate (in different quantities) on a composting
      process was investigated. The digestate was prepared in a pilot-scale 500L high
      solids dry anaerobic digester and composting was completed in eight 25L reactors
      with different ratios of digestate to fresh feedstock from the organic fraction
      of municipal solid waste (OFMSW). The digestate constituted 0, 10, 20, 30, 40,
      50, 75, or 100% (wet mass) of the feedstock. The co-composting experiment was
      conducted in two phases: active aeration and curing. Monitored parameters
      included: process temperature, aeration rate, oxygen concentration of the outlet
      gas, mass changes, total solids, organic matter, pH, and electrical conductivity.
      In addition, respirometry, C:N ratio, ammonium to nitrate ratio, and Solvita(r)
      tests were used to quantify stability and maturity end points. The results showed
      that the addition of digestate to the OFMSW increased composting reaction rates
      in all cases, with peak performance occurring within the ratio of 20-40% of
      digestate addition on a wet weight basis. Reactor performance may have been
      influenced by the high total ammonia nitrogen (TAN) levels in the digestate.
      Composting rates increased as TAN levels increased up to 5000 TAN mgkg-1DM;
      however, TAN may have become inhibitory at higher levels.

PMID- 28751176
TI  - The effect of interactive reminders on medication adherence: A randomized trial.
AB  - Expanding on evidence that interventions to improve health are more effective
      when informed by behavioral science, we explore whether reminders designed to
      harness behavioral science principles can improve medication adherence. We
      conducted a randomized controlled trial with 46,581 U.S. participants with
      commercial or Medicare Advantage insurance from Humana. Participants were
      randomly assigned to one of four experimental conditions. Participants in the
      usual care condition only received standard mailings that the insurer usually
      sends. In addition to the standard mailings, participants in the other three
      conditions also received (1) mailings that reminded them to take a target
      medication (basic reminder condition), (2) reminders that prompted them to
      predict their medication adherence in the next 30days (prediction condition), or
      (3) reminders that prompted them to commit to a self-determined level of
      adherence for the next 30days (commitment condition). We sent these mailings once
      a month for three months from November, 2014 through January, 2015, and tracked
      prescription refills. We find that, during the mailing period, reminders
      increased adherence by 0.95 percentage points (p<0.05), and this effect was
      driven by the prediction and commitment conditions; during the three-month post
      mailing period, reminders increased adherence by 0.98 percentage points (p<0.05),
      and this effect was driven by the basic reminder and commitment conditions. The
      reminders increased medication adherence by 0.7 pills per dollar spent over our
      181day study period. Trial registry name: Effect of Reminders on Adherence.
      Registration identification number: NCT02411006 URL for the registry:
      https://clinicaltrials.gov/ct2/show/NCT02411006.

PMID- 28751177
TI  - In vitro screening of the open source Pathogen Box identifies novel compounds
      with profound activities against Neospora caninum.
AB  - Neospora caninum is a major cause of abortion in cattle and represents an
      important veterinary health problem of great economic significance. The Medicines
      for Malaria Venture (MMV) Pathogen Box, an open-source collection of 400
      compounds with proven anti-infective properties against a wide range of
      pathogens, was screened against a N. caninum beta-galactosidase reporter strain
      grown in human foreskin fibroblasts. A primary screening carried out at 1uM
      yielded 40 compounds that were effective against N. caninum tachyzoites. However,
      30 of these compounds also affected the viability of the host cells. The 10
      remaining compounds exhibited IC50 values between 4 and 43nM. Three compounds
      with IC50 values below 10nM, namely MMV676602, MMV688762 and MMV671636, were
      further characterized in vitro in more detail with respect to inhibition of
      invasion versus intracellular proliferation, and only MMV671636 had an impact on
      intracellular proliferation of tachyzoites. This was confirmed by transmission
      electron microscopy, showing that the primary target of MMV671636 was the
      mitochondrion. MMV671636 treatment of experimentally infected mice significantly
      reduced the number of animals with lung and brain infection, and these mice also
      exhibited a significantly reduced titer of antibodies directed against N. caninum
      antigens. Thus, MMV671636 is a promising starting point for the development of a
      future neosporosis therapy.

PMID- 28751179
TI  - External carotid artery sacrifice in the treatment of infantile
      haemangiopericytoma in a neonate.
AB  - Haemangiopericytoma of the head and neck (HN-HPC) is a rare neoplasm occurring in
      children. The rarity of the tumour poses a diagnostic and therapeutic challenge.
      Despite protocols that recommend the use of chemotherapy prior to surgery, no
      treatment standard has yet been proposed. This article reports the case of a 5
      month-old infant with a rapidly growing, giant life-threatening HN-HPC that was
      treated successfully by two-stage surgery without adjuvant chemotherapy.

PMID- 28751178
TI  - Acute action of rotenone on excitability of catecholaminergic neurons in rostral
      ventrolateral medulla.
AB  - The degeneration of the rostral ventrolateral medulla (RVLM) catecholaminergic
      neurons was responsible for some cardiovascular symptoms in Parkinson's disease
      (PD). Our previous study had observed the impairment of these neurons in the
      early stage of PD in the rotenone-induced PD rat model, but the related
      mechanisms remain unclear. Rotenone is a mitochondrial inhibitor, influencing the
      neuronal electrophysiological activity through activation of K-ATP channels that
      potentially participate in cell death processes. In the present study, effects of
      rotenone on electrophysiological properties of RVLM catecholaminergic neurons and
      its underlying mechanisms were investigated. In coronal slices of brain
      containing the RVLM through patch clamp technique, rotenone (0.5MUM) induced
      gradual postsynaptic inhibition on the spontaneous firing and cell membrane
      hyperpolarization with outward currents of catecholaminergic neurons. The
      electrophysiological changes were blocked by glibenclamide (30MUM), a blocker of
      K-ATP channels, and were nearly unchanged by diazoxide (100MUM), an opener of K
      ATP channels. Our results also showed that effects of rotenone on
      catecholaminergic neurons including reactive oxygen species (ROS) generation were
      prevented by pretreatment of coenzyme Q10 (CoQ10, 100MUM), a scavenger of ROS.
      These suggest that rotenone-induced electrophysiological changes of RVLM
      catecholaminergic neurons are caused by the opening of K-ATP channels, which are
      partly related to ROS generation. The changes of K-ATP channels might account for
      the vulnerability of RVLM catecholaminergic neurons.

PMID- 28751180
TI  - Outcomes of office-based temporomandibular joint arthroscopy: a 5-year
      retrospective study.
AB  - Temporomandibular joint (TMJ) arthroscopy is a minimally invasive surgical
      approach for intra-articular TMJ diseases. Office-based arthroscopy using the
      smallest TMJ scope allows for good visualization, as well as the ability to
      lavage the joint in an office setting. This study aimed to assess the efficacy of
      an office-based TMJ arthroscopic technique. A retrospective evaluation of 363
      patients with a TMJ disorder was performed. These patients underwent office-based
      arthroscopy using the OnPoint 1.2mm Scope System (Biomet Microfixation,
      Jacksonville, FL, USA) in Florida, USA, from July 2007. The following outcomes of
      the procedure were assessed: improvement in painless range of mandibular motion,
      pain on loading, and functional jaw pain; these were evaluated using a visual
      analog scale (VAS) over an average follow-up period of 263.81+/-142.1 days. The
      statistical analysis was performed using IBM SPSS Statistics version 20.
      Statistically significant improvements in TMJ pain and function, and other
      variables (P=0.001) were shown following TMJ arthroscopic lysis and lavage.
      Office-based arthroscopy using the OnPoint System was demonstrated to be a safe
      and efficient procedure for the treatment of patients with TMJ disorders as the
      first level of the algorithm of care.

PMID- 28751181
TI  - Short implants (6mm) vs. vertical bone augmentation and standard-length implants
      (>=9mm) in atrophic posterior mandibles: a 5-year retrospective study.
AB  - This retrospective study compared the 5-year clinical and radiographic outcomes
      of short implants (6 mm) (short group), and standard-length implants (>=9mm)
      placed after a vertical augmentation with autologous bone blocks (augmentation
      group), supporting partial fixed prostheses in the posterior mandible. Forty-five
      partially edentulous patients were enrolled in the study and evaluated after 5
      years: 22 (51 implants) in the augmentation group and 23 (46 implants) in the
      short group. Eight surgical complications occurred in the augmentation group
      versus none in the short group (P=0.003). One short implant failed before loading
      and one standard-length implant failed after 4 years because of peri-implantitis
      (P=1.0). Eight biological and two prosthetic complications occurred in the
      augmentation group vs. three biological and three prosthetic complications in the
      short group (P=0.09 and P=1.0, respectively). A mean marginal bone loss of 1.61+/
      1.12mm in the augmentation group and 0.68+/-0.68mm in the short group was found
      (P=0.002). Within the limitations of this study, both techniques resulted in
      successful clinical results after 5 years, but short implants exhibited less
      surgical complications and marginal bone loss than standard-length implants
      placed in augmented bone.

PMID- 28751182
TI  - Unilateral blindness after orthognathic surgery: hypotensive anaesthesia is not
      the primary cause.
AB  - Perioperative vision loss in non-ocular surgery represents a rare but devastating
      complication and multiple causes have been proposed. Any portion of the visual
      system may be involved and several authors have tried to relate that complication
      with deliberate hypotension anaesthetic technique, used to control intraoperative
      bleeding. We report a patient operated for orthognathism who suffered unilateral
      blindness. After review of similar cases, we can state that the transmission of
      forces generated during Le fort I osteotomy is related to the complication. This
      osteotomy technique is regularly performed in our hospital using a curved
      osteotome to achieve the pterygomaxillary disjunction and the adverse
      transmission of forces via the sphenoid bone is the main reason for indirect
      damage to the optic nerve and its vascular structures causing the neuropathy and
      blindness. Hypotensive anaesthesia may certainly lead to transient ischaemia but
      only in specific cases because of decreased ocular perfusion pressured.

PMID- 28751183
TI  - Three-dimensional aesthetic assessment of class II patients before and after
      orthognathic surgery and its association with quantitative surgical changes.
AB  - The aim of this study was to compare evaluations of the aesthetic outcome of
      class II orthognathic patients, as performed by observers with varying expertise
      using three-dimensional (3D) facial images, and to examine the relationship of
      aesthetic ratings in relation to quantitative surgical changes. Pre- and
      postoperative 3D facial images of 20 surgically treated class II patients (13
      female, 7 male) were assessed for aesthetics by orthodontists, maxillofacial
      surgeons, and laypeople. Attractiveness ratings for the lips, chin, and overall
      facial aesthetics were evaluated on a 5-point Likert scale. Correlation between
      the aesthetic scores was obtained and quantitative surgical changes were
      examined. For all groups of observers, significant improvements in attractiveness
      scores were found, especially for the chin assessment. Orthodontists perceived
      the greatest improvement and laypeople the smallest. Overall, laypeople scored
      higher with less variability, but with lower intra- and inter-observer agreement.
      No significant correlation was found between the aesthetic improvement and soft
      tissue surgical changes. To avoid patient dissatisfaction, it is important to
      bear in mind that the demands and perception of aesthetic improvement after
      orthognathic surgery are higher for clinicians than for the general public.

PMID- 28751184
TI  - Restoration of Sleep Architecture after Maxillomandibular Advancement: Success
      Beyond the Apnea-Hypopnea Index.
AB  - While effects of maxillomandibular advancement (MMA) on respiratory parameters
      for patients with obstructive sleep apnea (OSA) are well described, effects on
      sleep architecture before and after MMA are not. A retrospective cohort analysis
      on sleep architecture was examined in 10 OSA patients who underwent MMA surgery
      between July 2013 and November 2014, and had prespecified complete
      polysomnography (PSG) datasets. Sleep stages were examined relative to a Western
      European population-based control group. All of the respiratory parameters
      improved significantly post MMA. Rapid eye movement (REM) latency decreased from
      178.0+/-142.8 to 96.6+/-64.5min (P=0.035). %NREM (non-rapid eye movement)1
      (P=0.045) and %WASO (wakefulness after sleep onset) (P=0.006) decreased, while
      %REM increased (P=0.002) after MMA. WASO decreased from 64.2+/-57min to 22.4+/
      15.4min (P=0.017). Preoperatively, OSA subjects showed significantly lower sleep
      efficiency (P=0.016), sleep onset latency (P=0.015), and % REM (P<0.001) than the
      normative population dataset, while post MMA there was a significant decrease in
      %NREM1 sleep (P<0.001) and in %WASO (P<0.001). MMA results in a marked decrease
      in WASO and increase in REM, and to a lesser extent NREM sleep. Patients after
      MMA show values similar to population controls except for a lower WASO.

PMID- 28751185
TI  - Genome-wide association mapping of latex yield and girth in Amazonian accessions
      of Hevea brasiliensis grown in a suboptimal climate zone.
AB  - Latex yield and growth are the key complex traits in commercial rubber
      production. The present study is the first to report genome-wide association
      mapping of latex yield and girth, for 170 Amazonian accessions grown in a
      suboptimal area characterized by limited rainfall and a lengthy dry season.
      Targeted sequence enrichment to capture gene transcripts generated 14,155 high
      quality filtered single nucleotide polymorphisms (SNPs) of which 94.3% resided in
      coding regions. The rapid decay of linkage disequilibrium over physical and
      genetic distance found in the accessions was comparable to those previously
      reported for several outcrossing species. A mixed linear model detected three
      significant SNPs in three candidate genes involved in plant adaptation to drought
      stress, individually explaining 12.7-15.7% of the phenotypic variance. The SNPs
      identified in the study will help to extend understanding, and to support genetic
      improvement of rubber trees grown in drought-affected regions.

PMID- 28751186
TI  - The Science of Selection: Using Best Practices From Industry to Improve Success
      in Surgery Training.
AB  - BACKGROUND: The selection of high-quality applicants is critical to the future of
      surgery. However, it is unclear if current practices meet industry criteria of a
      successful selection system, as measured by administrative efficiency and
      performance and attrition of those selected. METHODS: We performed a modified
      systematic review process to gain an understanding of current selection
      processes, remediation practices, and attrition rates in surgery residency
      training programs in the United States. We also conducted semistructured
      interviews with local residency program directors and coordinators to obtain a
      specific snapshot of the amount of time and resources dedicated to these
      activities in various sized programs. The associated financial costs of these
      activities are also presented. RESULTS: The administrative costs for current
      residency selection processes are substantial, ranging from $45,000 to $148,000
      for each program per year. Approximately 30% of residents require at least 1
      remediation intervention, costing programs $3400 to $5300 per episode, and
      typically involve concerns around nontechnical skills. Attrition rates range from
      20% to 40%. CONCLUSIONS: This review suggests that additional methodologies may
      allow surgery residency programs to identify best-fit candidates more efficiently
      and effectively, while also decreasing remediation and attrition rates. Possible
      solutions include incorporation of structured interviews, personality
      inventories, and situational judgment tests. Resources dedicated to current
      interview practices, remediation efforts, and attrition management can be
      redirected to support these methodologies. By applying the science of selection
      and assessment to the recruitment process, programs may be able to make more data
      driven decisions to identify candidates who will be successful at their
      institution.

PMID- 28751187
TI  - Immunotherapy in Multiple Myeloma.
AB  - OBJECTIVES: To review the use of monoclonal antibodies (mAbs) in the treatment of
      multiple myeloma (MM) and the management of most common side effects. DATA
      SOURCES: Review of journal articles related to mAbs in MM. CONCLUSION: The
      therapeutic options for MM have improved dramatically and the development of mAbs
      has been associated with improvement in clinical outcomes and favorable toxicity
      profiles. IMPLICATIONS FOR NURSING PRACTICE: With appropriate pre-medications and
      nursing management, mAbs are a well-tolerated treatment option for myeloma
      patients.

PMID- 28751188
TI  - The Experience of Myeloma Caregivers During Home-Based Oral Chemotherapy
      Treatment: A Qualitative Study.
AB  - OBJECTIVE: The primary aim of this qualitative study was to explore myeloma
      carers/caregivers experience during outpatient-based oral treatment for patients
      with multiple myeloma (MM). DATA SOURCES: Literature review. In-depth, open-ended
      interviews of seven purposively selected caregivers of MM patients in the United
      Kingdom. CONCLUSION: Findings showed that carers were involved in practical and
      emotional caregiving activities, assisting the patient with managing complex oral
      combination treatments, and monitoring side effects. Care-giving activities
      continued after treatment, and experiences were described within the context of
      the MM journey and fear and uncertainty about the future. Caregivers also
      experienced a range of emotions, which they often kept hidden from the MM
      patients and other family members. Difficulties balancing caring
      responsibilities, particularly for those with jobs, were expressed. IMPLICATIONS
      FOR NURSING PRACTICE: Nurses need to understand the importance of considering
      carers' involvement when assessing patients, and the need to address caregivers'
      continuing support and information needs. Problems navigating health and social
      care processes should be anticipated, and nurses can direct the carers to
      appropriate resources to meet their needs.

PMID- 28751189
TI  - Targeted therapies in hematological malignancies using therapeutic monoclonal
      antibodies against Eph family receptors.
AB  - The use of monoclonal antibodies (mAbs) and molecules derived from them has
      achieved considerable attention and success in recent years, establishing this
      mode of therapy as an important therapeutic strategy in many cancers, in
      particular hematological tumors. mAbs recognize cell surface antigens expressed
      on target cells and mediate their function through various mechanisms such as
      antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, or
      immune system modulation. The efficacy of mAb therapy can be improved when they
      are conjugated to a highly potent payloads, including cytotoxic drugs and
      radiolabeled isotopes. The Eph family of proteins has received considerable
      attention in recent years as therapeutic targets for treatment of both solid and
      hematological cancers. High expression of Eph receptors on cancer cells compared
      with low expression levels in normal adult tissues makes them an attractive
      candidate for cancer immunotherapy. In this review, we detail the modes of action
      of antibody-based therapies with a focus on the Eph family of proteins as
      potential targets for therapy in hematological malignancies.

PMID- 28751190
TI  - Septin 6 regulates engraftment and lymphoid differentiation potential of murine
      long-term hematopoietic stem cells.
AB  - Septins are a family of filament-forming GTP-binding proteins that serve as
      scaffolds and diffusion barriers in various cellular processes. Septin 6 is known
      as a fusion partner of mixed-lineage leukemia in infant acute myeloid leukemia.
      The occurrence of the fusion gene is associated with a reduced expression of
      septin 6 itself. The role of septin 6 in hematopoiesis and whether it is involved
      in scaffolds within hematopoietic cells is not known. Septin 6-deficient
      hematopoietic stem cells (HSCs) present with an increased engraftment potential
      but altered lymphoid differentiation with a reduced contribution to the T-cell
      compartment and an increased B-cell contribution. Although multipotent progenitor
      cells showed a very distinct septin 6 filament organization and intracellular
      distribution, their function was not impaired by septin 6 deficiency. Our data
      therefore suggest a regulatory role for septin 6 in long-term HSC function and
      lymphoid lineage differentiation.

PMID- 28751191
TI  - Minimal clinically important difference of the Modified Fatigue Impact Scale in
      Parkinson's disease.
AB  - OBJECTIVE: Fatigue is a common and debilitating symptom of Parkinson's disease
      (PD) with no evidence-based treatments. While several fatigue scales are
      partially validated in PD the minimal clinically important difference (MCID) is
      unknown for any scale but is an important psychometric value to design and
      interpret therapeutic trials. We thus sought to determine the MCID for the
      Modified Fatigue Impact Scale (MFIS). METHODS: This is a secondary data analysis
      from 94 PD participants in an acupuncture trial for PD fatigue. Standard
      psychometric approaches were used to establish validity and an anchor-based
      approach was used to determine the MCID. RESULTS: The MFIS demonstrated good
      concurrent validity with other outcome measures and high internal consistency.
      MCIDs values were found to be 13.8, 6.8 and 6.2 for the MFIS total, MFIS
      cognitive, and MFIS physical subscores respectively. CONCLUSIONS: The MFIS is a
      valid multidimensional measure of fatigue in PD with demonstrable MCID.

PMID- 28751192
TI  - Evidence of an inverse correlation between serotonergic activity and spreading
      depression propagation in the rat cortex.
AB  - Various neurological and psychiatric diseases lead to alterations in cortical
      serotonergic activity as one of their underlying processes. However, the
      electrophysiological implication of changes in serotonergic activity remains a
      matter of investigation. In this study, we investigated whether brain
      serotonergic activity influences the excitability-related phenomenon known as
      cortical spreading depression (CSD). CSD parameters (propagation velocity, and
      amplitude and duration of the DC-shift) was evaluated in rats that received two
      treatments that increased cortical serotonergic activity, electrical stimulation
      of the raphe nuclei and subcutaneous injection of a selective serotonin reuptake
      inhibitor, sumatriptan. A third group of rats was tested on a low-tryptophan diet
      rat model of serotonin depletion. Control rats for these three groups received,
      respectively, sham raphe stimulation, saline injection, and a tryptophan
      supplemented diet. Compared to controls, electrical stimulation of the raphe
      nuclei and sumatriptan administration decelerated CSD and increased the duration
      of the negative DC-shift of CSD, whereas the low-tryptophan diet was associated
      with significantly accelerated CSD propagation and shortened DC-shift of CSD
      (p<0.05). We concluded that serotonergic neurons are very important for
      stabilizing the delicate equilibrium between excitatory and inhibitory neuronal
      influences that determines cortical excitability and CSD propagation. Our
      pharmacological, electrophysiological and dietary data suggest that cortical
      serotonergic activity negatively modulates CSD propagation in the rat cortex.
      Reduced central serotonergic activity, as can be observed in several neurological
      and psychiatric diseases, may constitute a pathological factor for increased
      sensitivity to CSD.

PMID- 28751193
TI  - MicroRNA-33a and let-7e inhibit human colorectal cancer progression by targeting
      ST8SIA1.
AB  - Colorectal cancer (CRC) is one of the leading causes of cancer mortality
      worldwide. Aberrant sialylation is crucially involved in the progression of
      various types of cancer. MicroRNAs (miRNAs) have been broadly studied in cancer.
      MicroRNA-33a (miR-33a) and Has-let-7e (let-7e) are non-coding RNA that can reduce
      cell motility and viability in cancer. In this study, miR-33a and let-7e levels
      were confirmed to be significantly down-regulated in CRC samples (n=32) and drug
      resistant cell line (HCT-8/5-FU) compared with those in the matched adjacent
      tissues and drug sensitivity cell line (HCT-8). ST8SIA1 was highly expressed in
      CRC tissues and HCT-8/5-FU cells, which was negatively correlated with miR
      33a/let-7e expression. Luciferase reporter assays confirmed that both miR-33a and
      let-7e bound to the 3'-untranslated (3'-UTR) region of ST8SIA1. Inhibiting miR
      33a/let-7e expression in CRC cells increased endogenous ST8SIA1 mRNA and protein
      levels. MiR-33a/let-7e knockdown promoted chemoresistance, proliferation,
      invasion, angiogenesis in vitro, and tumor growth in vivo. Whereas, ectopic
      expression of miR-33a/let-7e suppressed chemoresistance, proliferation, invasion
      and angiogenesis in CRC cell lines. ST8SIA1 knockdown mimicked the tumor
      suppressive effect of miR-33a/let-7e on CRC cells, while restoration of ST8SIA1
      abolished the tumor suppressive effect of miR-33a/let-7e on CRC cells. Taken
      together, altered expression of miR-33a/let-7e was correlated with ST8SIA1 level,
      which might contribute to CRC progression. The miR-33a/let-7e-ST8SIA1 axis could
      be a therapeutic target for CRC patients.

PMID- 28751194
TI  - Biaxial loading of arterial tissues with 3D in situ observations of adventitia
      fibrous microstructure: A method coupling multi-photon confocal microscopy and
      bulge inflation test.
AB  - Disorders in the wall microstructure underlie all forms of vascular disease, such
      as the aortic aneurysm, the rupture of which is necessarily triggered at the
      microscopic level. In this context, we developed an original experimental
      approach, coupling a bulge inflation test to multiphoton confocal microscopy, for
      visualizing the 3D micro-structure of porcine, human non-aneurysmal and
      aneurysmal aortic adventitial collagen under increasing pressurization. The
      experiment complexity on such tissues led to deeply address the acquisition major
      hurdles. The important innovative features of the methodology are presented,
      especially regarding region-of-interest tracking, definition of a stabilization
      period prior to imaging and correction of z-motion, z being the objective's axis.
      Such corrections ensured consistent 3D qualitative and quantitative analyses
      without z-motion. Qualitative analyses of the stable 3D images showed dense
      undulated collagen fiber bundles in the unloaded state which tended to
      progressive straightening and separation into a network of thinner bundles at
      high pressures. Quantitative analyses were made using a combination of weighted
      2D structure tensors and fitting of 4 independent Gaussian functions to measure
      parameters related to straightening and orientation of the fibers. They denoted 3
      principal fibers directions, approximately 45 degrees , 135 degrees  and 90
      degrees  with respect to the circumferential axis in the circumferential-axial
      plane without any evident reorientation of the fibers under pressurization.
      Results also showed that fibers at zero-pressure state were straighter and less
      dispersed in orientation for human samples - especially aneurysms - than for
      pigs. Progressive straightening and decrease in dispersion were quantified during
      the inflation. These findings provide further insight into the micro
      architectural changes within the arterial wall.

PMID- 28751195
TI  - Antinociceptive, antiallodynic and antihyperalgesic effects of the 5-HT1A
      receptor selective agonist, NLX-112 in mouse models of pain.
AB  - BACKGROUND AND PURPOSE: NLX-112 (a.k.a. befiradol, F13640) is a drug candidate
      intended for the treatment of l-DOPA-induced dyskinesia. It is a highly selective
      serotonin 5-HT1A receptor full agonist which has been previously tested in a
      variety of models of CNS effects including analgesic activity in rat. Its
      activity in mouse models of pain has not been previously investigated.
      EXPERIMENTAL APPROACH: The activity of NLX-112 was tested in mouse models of
      acute pain (hot plate), tonic pain (intraplantar formalin test), in the
      oxaliplatin-induced neuropathic pain model of chemotherapy-induced peripheral
      neuropathy and in the streptozotocin (STZ)-induced model of painful diabetic
      neuropathy. KEY RESULTS: The main findings indicate that (i) NLX-112 was markedly
      active in the formalin test with potent reduction of paw licking in both phases
      of the test (minimal effective dose (MED) 0.5 mg/kg i.p. and p.o. in acute phase,
      and 0.1 mg/kg i.p. and 1 mg/kg p.o. in late phase). The effects of NLX-112 in
      this test were completely abolished by the selective 5-HT1A receptor antagonist,
      WAY100635; (ii) NLX-112 was active in the hot plate test and in the oxaliplatin
      induced neuropathic pain model of chemotherapy-induced peripheral neuropathy, but
      at markedly higher doses (MED 2.5 mg/kg i.p.); (iii) NLX-112 was least active in
      the STZ-induced model of painful diabetic neuropathy (MED 5 mg/kg i.p.); (iv) NLX
      112 did not affect locomotor activity. CONCLUSIONS AND IMPLICATIONS: NLX-112 may
      have significant potential for treatment of tonic pain but may be less promising
      as a candidate for treatment of chemotherapy-induced or diabetic neuropathic
      pain.

PMID- 28751197
TI  - Development of a stereoselective and scalable process for the preparation of a
      methylcyclobutanol-pyridyl ether.
AB  - The evolution of a scalable process for the preparation of methylcyclobutanol
      pyridyl ether 1 is described. Key aspects of this development including careful
      control of the stereochemistry, elimination of chromatography, and application to
      kilogram-scale synthesis are addressed.

PMID- 28751196
TI  - Discovery of spiro[indole-3,2'-pyrrolidin]-2(1H)-one based inhibitors targeting
      Brr2, a core component of the U5 snRNP.
AB  - Bad response to refrigeration 2 (Brr2) is a member of the Ski2-like RNA
      helicases, and an essential component of the U5 small nuclear ribonucleoprotein
      (snRNP). A particularly important role of Brr2 is the ATP-dependent unwinding of
      the U4/U6 RNA duplex, which is a critical step in spliceosomal activation.
      Despite its biological importance, selective inhibitor for Brr2 had not been
      reported until our recent report. Here, we describe novel and structurally
      distinct spiro[indole-3,2'-pyrrolidin]-2(1H)-one based Brr2 inhibitors with
      superior activity to the previously reported 4,6-dihydropyrido[4,3-d]pyrimidine
      2,7(1H,3H)-dione series. Using an RNA dependent ATPase assay as a guide, high
      throughput screening, hit validation by structure-activity relationship (SAR)
      study, and subsequent chemical optimization to increase the ATPase inhibitory
      activity were performed. Thereafter, selectivity and helicase inhibitory activity
      of optimized compounds were confirmed. In the course of the study, compounds were
      synthesized using a three-component reaction, which accelerated the optimization
      process. All these efforts finally culminated in the discovery of the potent and
      selective Brr2 inhibitors (32a and 33a) exhibiting helicase inhibitory activity
      at submicromolar concentrations. Thus, compounds 32a and 33a could be valuable
      molecular probes to study the functions of Brr2 and molecular machinery of RNA
      splicing.

PMID- 28751198
TI  - Brassinolide-like activity of castasterone analogs with varied side chains
      against rice lamina inclination.
AB  - Brassinolide (BL) and castasterone (CS) are the representative members of
      brassinosteroid class of plant steroid hormone having plant growth promoting
      activity. In this study, eleven CS analogs bearing a variety of side chains were
      synthesized to determine the effect of the side chain structures on the BL-like
      activity. The plant hormonal activity was evaluated in a dwarf rice lamina
      inclination assay, and the potency was determined as the reciprocal logarithm of
      the 50% effective dose (ED50) from each dose-response curve. The reciprocal
      logarithm of ED50 (pED50) was decreased dramatically upon deletion of the C-28
      methyl group of CS. The introduction of oxygen-containing groups such as hydroxy,
      methoxy, and ethoxycarbonyl was also unfavorable to the activity. The pED50 was
      influenced by the geometry of carbon-carbon double bond between C-24 and C-25
      (cis and trans), but the introduction of a fluorine atom at the C-25 position of
      the double bond did not significantly change the activity. The binding free
      energy (DeltaG) was calculated for all ligand-receptor binding interactions using
      molecular dynamics, resulting that DeltaG is linearly correlated with the pED50.

PMID- 28751199
TI  - alpha-Geminal disubstituted pyrrolidine iminosugars and their C-4-fluoro
      analogues: Synthesis, glycosidase inhibition and molecular docking studies.
AB  - A simple strategy for the synthesis of alpha-geminal disubstituted pyrrolidine
      iminosugars 3a-c and their C-4 fluorinated derivatives 4a-c has been described
      from d-glucose. The methodology involves the Corey-Link and Jocic-Reeve reaction
      with 3-oxo-alpha-d-glucofuranose and nucleophilic displacement reaction to get
      the furanose fused pyrrolidine ring skeleton with requisite CH2OH/CO2H
      functionalities at C-3. The fluorine substituent in target molecules was
      introduced by nucleophilic displacement of -OTf in 9a/9c with CsF. Appropriate
      manipulation of the anomeric carbon in the furanose fused pyrrolidine ring
      skeleton afforded alpha-geminal disubstituted pyrrolidine iminosugars 3a-c and C
      4 fluoro derivatives 4a-c. The pyrrolidine iminosugars 3a and 3c were found to be
      potent inhibitors of alpha-galactosidase while, the fluoro derivatives 4a and 4b
      showed strong inhibition of beta-glucosidase and beta-galactosidase,
      respectively. These results were substantiated by in silico molecular docking
      studies.

PMID- 28751200
TI  - Gene regulation in adult neural stem cells. Current challenges and possible
      applications.
AB  - Adult neural stem and progenitor cells (NSPCs) offer a unique opportunity for
      neural regeneration and niche modification in physiopathological conditions,
      harnessing the capability to modify from neuronal circuits to glial scar.
      Findings exposing the vast plasticity and potential of NSPCs have accumulated
      over the past years and we currently know that adult NSPCs can naturally give
      rise not only to neurons but also to astrocytes and reactive astrocytes, and
      eventually to oligodendrocytes through genetic manipulation. We can consider
      NSPCs as endogenous flexible tools to fight against neurodegenerative and
      neurological disorders and aging. In addition, NSPCs can be considered as active
      agents contributing to chronic brain alterations and as relevant cell populations
      to be preserved, so that their main function, neurogenesis, is not lost in damage
      or disease. Altogether we believe that learning to manipulate NSPC is essential
      to prevent, ameliorate or restore some of the cognitive deficits associated with
      brain disease and injury, and therefore should be considered as target for future
      therapeutic strategies. The first step to accomplish this goal is to target them
      specifically, by unveiling and understanding their unique markers and signaling
      pathways.

PMID- 28751201
TI  - The role of mucus in cell-based models used to screen mucosal drug delivery.
AB  - The increasing interest in developing tools to predict drug absorption through
      mucosal surfaces is fostering the establishment of epithelial cell-based models.
      Cell-based in vitro techniques for drug permeability assessment are less
      laborious, cheaper and address the concerns of using laboratory animals.
      Simultaneously, in vitro barrier models that thoroughly simulate human epithelia
      or mucosae may provide useful data to speed up the entrance of new drugs and new
      drug products into the clinics. Nevertheless, standard cell-based in vitro models
      that intend to reproduce epithelial surfaces often discard the role of mucus in
      influencing drug permeation/absorption. Biomimetic models of mucosae in which
      mucus production has been considered may not be able to fully reproduce the
      amount and architecture of mucus, resulting in biased characterization of
      permeability/absorption. In these cases, artificial mucus may be used to
      supplement cell-based models but still proper identification and quantification
      are required. In this review, considerations regarding the relevance of mucus in
      the development of cell-based epithelial and mucosal models mimicking the gastro
      intestinal tract, the cervico-vaginal tract and the respiratory tract, and the
      impact of mucus on the permeability mechanisms are addressed. From simple
      epithelial monolayers to more complex 3D structures, the impact of the presence
      of mucus for the extrapolation to the in vivo scenario is critically analyzed.
      Finally, an overview is provided on several techniques and methods to
      characterize the mucus layer over cell-based barriers, in order to intimately
      reproduce human mucosal layer and thereby, improve in vitro/in vivo correlation.

PMID- 28751203
TI  - Simple algorithm for the correction of MRI image artefacts due to random phase
      fluctuations.
AB  - PURPOSE: Fast Field-Cycling (FFC) MRI is a novel technology that allows varying
      the main magnetic field B0 during the pulse sequence, from the nominal field
      (usually hundreds of millitesla) down to Earth's field or below. This technique
      uses resistive magnets powered by fast amplifiers. One of the challenges with
      this method is to stabilise the magnetic field during the acquisition of the NMR
      signal. Indeed, a typical consequence of field instability is small, random phase
      variations between each line of k-space resulting in artefacts, similar to those
      which occur due to homogeneous motion but harder to correct as no assumption can
      be made about the phase error, which appears completely random. Here we propose
      an algorithm that can correct for the random phase variations induced by field
      instabilities without prior knowledge about the phase error. METHODS: The
      algorithm exploits the fact that ghosts caused by field instability manifest in
      image regions which should be signal free. The algorithm minimises the signal in
      the background by finding an optimum phase correction for each line of k-space
      and repeats the operation until the result converges, leaving the background free
      of signal. CONCLUSION: We showed the conditions for which the algorithm is robust
      and successfully applied it on images acquired on FFC-MRI scanners. The same
      algorithm can be used for various applications other than Fast Field-Cycling MRI.

PMID- 28751202
TI  - R1rho dispersion and sodium imaging in human calf muscle.
AB  - PURPOSE: To evaluate the magnitude of chemical exchange effects and R1rho
      dispersion in muscle and their relationship to tissue sodium levels with aging.
      METHODS: Seven healthy volunteers (aged 24 to 87years, median age 47) underwent
      MRI to assess tissue sodium levels and water T1rho values at different spin
      locking frequencies in calf muscles. T1rho values at each locking field were
      computed based on a three-parameter mono-exponential model to fit signals
      obtained at different locking times, and R1rho (=1/T1rho) rates were compared at
      different locking fields. In particular, the dispersion of R1rho
      (DeltaR1rho=R1rho(0Hz)-R1rho(500Hz)) was examined as a function of subject age.
      Muscle sodium content was calculated by comparing signal intensities between
      tissues and reference standards within the same image. The variations of
      DeltaR1rho with age and sodium were analyzed by linear regression. RESULTS: T1rho
      values and sodium content both increased with age. R1rho dispersion also
      increased with age and showed a strong linear correlation (correlation
      coefficient r=0.98, P=0.000578) with sodium content. CONCLUSION: DeltaR1rho
      reports on the contribution of labile protons such as hydroxyls which may be
      associated with macromolecule accumulation in the extracellular matrix (ECM). An
      increase of sodium signal suggests an enlarged ECM volume fraction and/or an
      increase in sodium concentration, which occurs during normal aging. The strong
      correlation between DeltaR1rho and sodium is likely the consequence of increased
      ECM and density of total charged sites within the matrix from molecules such as
      collagens and proteoglycans. The results from this study show the potential use
      of R1rho dispersion and sodium imaging in the assessment of pathological changes
      in muscle such as fibrosis.

PMID- 28751204
TI  - Rapid acquisition of magnetic resonance imaging of the shoulder using three
      dimensional fast spin echo sequence with compressed sensing.
AB  - PURPOSE: To evaluate the feasibility of 3D fast spin-echo (FSE) imaging with
      compressed sensing (CS) for the assessment of shoulder. MATERIALS AND METHODS:
      Twenty-nine patients who underwent shoulder MRI including image sets of axial 3D
      FSE sequence without CS and with CS, using an acceleration factor of 1.5, were
      included. Quantitative assessment was performed by calculating the root mean
      square error (RMSE) and structural similarity index (SSIM). Two musculoskeletal
      radiologists compared image quality of 3D-FSE sequences without CS and with CS,
      and scored the qualitative agreement between sequences, using a five-point scale.
      Diagnostic agreement for pathologic shoulder lesions between the two sequences
      was evaluated. RESULTS: The acquisition time of 3D-FSE MRI was reduced using CS
      (3min 23s vs. 2min 22s). Quantitative evaluations showed a significant
      correlation between the two sequences (r=0.872-0.993, p<0.05) and SSIM was in an
      acceptable range (0.940-0.993; mean+/-standard deviation, 0.968+/-0.018).
      Qualitative image quality showed good to excellent agreement between 3D-FSE
      images without CS and with CS. Diagnostic agreement for pathologic shoulder
      lesions between the two sequences was very good (kappa=0.915-1). CONCLUSIONS: The
      3D-FSE sequence with CS is feasible in evaluating the shoulder joint with reduced
      scan time compared to 3D-FSE without CS.

PMID- 28751205
TI  - Central injection of a synthetic chicken partial leptin peptide does not affect
      food intake in chicks.
AB  - Leptin is an adipose tissue-derived hormone in mammals that plays an important
      role in whole body energy balance via its inhibitory effects on food intake
      mediated through the hypothalamus. Chicken leptin has a low sequence homology to
      mammalian leptin and its role in appetite regulation is not reported; hence the
      objective of this study was to determine effects of central injection of chicken
      leptin on food and water intake and associated behaviors in chicks. Chicks were
      intracerebroventricularly injected with 0 (vehicle), 0.3, 1.0, or 3.0 nmol of a
      synthetic chicken leptin partial peptide and food and water intake were
      monitored. There were no effects observed and a second experiment was conducted
      to evaluate food and water intake at higher doses; after injection of 0, 2.5,
      5.0, or 10.0 nmol leptin. Again, there were no effects on food or water intake.
      In the third experiment, behaviors were analyzed during the first 30 min post
      injection of vehicle or 10 nmol leptin. At 5 min post-injection, vehicle-injected
      chicks spent more time sitting than leptin-injected chicks. A wide dose range was
      evaluated however, the absence of an effect on food intake or behavior suggests
      that the chicken leptin peptide that was tested does not mediate effects on
      appetite in the brain and that chicken leptin likely has a different
      physiological role in birds than in mammals.

PMID- 28751206
TI  - Intravitreal injection of docosahexaenoic acid attenuated photoreceptor cell
      injury in a NaIO3-induced age-related macular degeneration rat model.
AB  - In most studies, the major supplement docosahexaenoic acid (DHA) is administered
      orally or intraperitoneally. In this study, we proposed to assess the safety and
      efficacy of the intravitreal injection of DHA in an age-related macular
      degeneration (AMD) rat model. Different concentrations of DHA were injected into
      the vitreous body. Histopathology and terminal deoxynucleotidyl transferase dUTP
      nick-end labeling (TUNEL) analysis showed that there was no difference in
      thickness, observable structure, or apoptosis among the untreated, normal saline,
      and DHA groups (0.2, 1.0, 5.0 and 10MUg). However, GFAP expression was increased
      in the 10MUg group. To investigate whether intravitreal injection of DHA could
      protect photoreceptors, we developed a NaIO3-induced retinal damage model in
      adult rats. Decreases in deformation and thickness were observed in the outer
      nuclear layer (ONL) after NaIO3 administration but were improved with DHA
      injection. The NaIO3 group showed a substantial reduction in the number of nuclei
      in ONL, whereas the DHA group showed an increase. Additionally, significant
      increases in SOD activity and Nrf2 expression were observed after DHA injection;
      GFAP and NF-kappaB expression levels were markedly decreased by DHA injection.
      Moreover, Western blotting showed that Bax, cleaved caspase-3 and CHOP were
      notably increased in the NaIO3 group but were significantly decreased by DHA
      injection. Collectively, intravitreal injection of DHA is safe and effective in
      select doses in a NaIO3-induced AMD rat model. The current results suggest that
      intravitreal injection of DHA may be a new avenue for the treatment of AMD.

PMID- 28751207
TI  - Analysis of the expression of HAX-1 gene in human glioma.
AB  - Glioma, as the most common aggressive malignant tumor in the central nervous
      system, is still an insurmountable issue in neural diseases. The proliferation
      and survival mechanism of glioma cells need to be explored further for the
      development of glioma treatment. Hematopoietic cell-specific protein 1 associated
      protein X-1 (HAX-1) is well known for its anti-apoptotic effect. It was reported
      to play an important role in several malignant tumors. However, the effect of HAX
      1 in glioma still remains unknown. This study aimed to investigate the expression
      of HAX-1 in glioma and the correlation between HAX-1 and the clinicopathological
      characteristics and prognosis of glioma. Quantitative reverse transcription
      polymerase chain reaction and Western blot analysis showed that HAX-1 was
      overexpressed in glioma cell lines compared with normal human astrocytes. This
      trend was confirmed by comparing the expression of HAX-1 in glioma tissues and
      nontumorous tissues. The study also analyzed the correlation between the
      expression of HAX-1 and clinicopathological characteristics of glioma and found
      the expression of HAX-1 to be highly related to the differentiation and World
      Health Organization stage of glioma tissues. The survival analysis revealed that
      HAX-1 was an independent prognostic factor. In conclusion, this novel study
      suggested that the overexpression of HAX-1 might contribute to the malignant
      progression of glioma.

PMID- 28751208
TI  - Response: First birth following spindle transfer.

PMID- 28751209
TI  - PKA activity exacerbates hypoxia-induced ROS formation and hypoxic injury in PC
      12 cells.
AB  - Hypoxia is a primary factor in many pathological conditions. Hypoxic cell death
      is commonly attributed to metabolic failure and oxidative injury. cAMP-dependent
      protein kinase A (PKA) is activated in hypoxia and regulates multiple enzymes of
      the mitochondrial electron transport chain, thus may be implicated in cellular
      energy depletion and hypoxia-induced cell death. Wild type (WT) PC-12 cells and
      PKA activity-deficient 123.7 PC-12 cells were exposed to 3, 6, 12 and 24h hypoxia
      (0.1% or 5% O2). Hypoxia, at 24h 0.1% O2, induced cell death and increased
      reactive oxygen species (ROS) in WT PC-12 cells. Despite lower ATP levels in
      normoxic 123.7 cells than in WT cells, hypoxia only decreased ATP levels in WT
      cells. However, menadione-induced oxidative stress similarly affected both cell
      types. While mitochondrial COX IV expression remained consistently higher in
      123.7 cells, hypoxia decreased COX IV expression in both cell types. N-acetyl
      cysteine antioxidant treatment blocked hypoxia-induced WT cell death without
      preventing ATP depletion. Transient PKA catalpha expression in 123.7 cells
      partially restored hypoxia-induced ROS but did not alter ATP levels or COX IV
      expression. We conclude that PKA signaling contributes to hypoxic injury, by
      regulating oxidative stress rather than by depleting ATP levels. Therapeutic
      strategies targeting PKA signaling may improve cellular adaptation and recovery
      in hypoxic pathologies.

PMID- 28751210
TI  - Melamine, beyond the kidney: A ubiquitous endocrine disruptor and neurotoxicant?
AB  - Melamine is commonly used in a variety of consumer products such as furniture,
      dining ware, and food utensils. The chemical infamously gained worldwide
      attention by its illegal addition to a variety of foodstuffs in order to falsify
      protein content, which led to serious, sometimes fatal, health impacts in
      children and pets. This resulted in a large amount of published primary studies
      and reviews of the impacts of melamine exposure on kidney function. However, a
      growing body of literature suggests that melamine may have impacts beyond renal
      dysfunction. We conducted a scoping review of this literature which yielded more
      than 40 studies with human, animal, and in vitro findings. Neurological impacts,
      reproductive function, and anthropometric outcomes were identified as possible
      candidates for systematic review based on evidence stream and replication of
      endpoints. The results of this analysis provide a basis for prioritizing future
      research on health impacts associated with melamine exposure.

PMID- 28751211
TI  - Microbial F-type lectin domains with affinity for blood group antigens.
AB  - F-type lectins are fucose binding lectins with characteristic fucose binding and
      calcium binding motifs. Although they occur with a selective distribution in
      viruses, prokaryotes and eukaryotes, most biochemical studies have focused on
      vertebrate F-type lectins. Recently, using sensitive bioinformatics search
      techniques on the non-redundant database, we had identified many microbial F-type
      lectin domains with diverse domain organizations. We report here the biochemical
      characterization of F-type lectin domains from Cyanobium sp. PCC 7001, Myxococcus
      hansupus and Leucothrix mucor. We demonstrate that while all these three
      microbial F-type lectin domains bind to the blood group H antigen epitope on
      fucosylated glycans, there are fine differences in their glycan binding
      specificity. Cyanobium sp. PCC 7001 F-type lectin domain binds exclusively to
      extended H type-2 motif, Myxococcus hansupus F-type lectin domain binds to B, H
      type-1 and Lewisb motifs, and Leucothrix mucor F-type lectin domain binds to a
      wide range of fucosylated glycans, including A, B, H and Lewis antigens. We
      believe that these microbial lectins will be useful additions to the
      glycobiologist's toolbox for labeling, isolating and visualizing glycans.

PMID- 28751212
TI  - Identification of three signaling molecules required for calcineurin-dependent
      monopolar growth induced by the DNA replication checkpoint in fission yeast.
AB  - Cell polarity is coordinately regulated with the cell cycle. Growth polarity of
      the fission yeast Schizosaccharomyces pombe transits from monopolar to bipolar
      during G2 phase, termed NETO (new end take off). Upon perturbation of DNA
      replication, the checkpoint kinase Cds1/CHK2 induces NETO delay through
      activation of Ca2+/calmodulin-dependent protein phosphatase calcineurin (CN). CN
      in turn regulates its downstream targets including the microtubule (MT) plus-end
      tracking CLIP170 homologue Tip1 and the Casein kinase 1gamma Cki3. However,
      whether and which Ca2+ signaling molecules are involved in the NETO delay remains
      elusive. Here we show that 3 genes (trp1322, vcx1 and SPAC6c3.06c encoding TRP
      channel, antiporter and P-type ATPase, respectively) play vital roles in the NETO
      delay. Upon perturbation of DNA replication, these 3 genes are required for not
      only the NETO delay but also for the maintenance of cell viability. Trp1322 and
      Vcx1 act downstream of Cds1 and upstream of CN for the NETO delay, whereas
      SPAC6c3.06c acts downstream of CN. Consistently, Trp1322 and Vcx1, but not
      SPAC6c3.06c, are essential for activation of CN. Interestingly, we have found
      that elevated extracellular Ca2+ per se induces a NETO delay, which depends on CN
      and its downstream target genes. These findings imply that Ca2+-CN signaling
      plays a central role in cell polarity control by checkpoint activation.

PMID- 28751213
TI  - Evaluation of dermal wound healing activity of synthetic peptide SVVYGLR.
AB  - SVVYGLR peptide (SV peptide) is a 7-amino-acid sequence with angiogenic
      properties that is derived from osteopontin in the extracellular matrix and
      promotes differentiation of fibroblasts to myofibroblast-like cells and the
      production of collagen type III by cardiac fibroblasts. However, the effects of
      SV peptide on dermal cells and tissue are unknown. In this study, we evaluated
      the effects of this peptide in a rat model of dermal wound healing. The synthetic
      SV peptide was added to dermal fibroblasts or keratinocytes, and their cellular
      motility was evaluated. In an in vivo wound healing exeriment, male rats aged 8
      weeks were randomly assigned to the SV peptide treatment, non-treated control, or
      phosphate-buffered saline (PBS) groups. Wound healing was assessed by its repair
      rate and histological features. Scratch assay and cell migration assays using the
      Chemotaxicell method showed that SV peptide significantly promoted the cell
      migration in both fibroblasts and keratinocytes. In contrast the proliferation
      potency of these cells was not affected by SV peptide. In the rat model, wound
      healing progressed faster in the SV peptide-treated group than in the control and
      PBS groups. The histopathological analyses showed that the SV peptide treatment
      stimulated the migration of fibroblasts to the wound area and increased the
      number of myofibroblasts. Immunohistochemical staining showed a marked increase
      of von Willebland factor-positive neomicrovessels in the SV peptide-treated
      group. In conclusion, SV peptide has a beneficial function to promote wound
      healing by stimulating granulation via stimulating angiogenesis, cell migration,
      and the myofibroblastic differentiation of fibroblasts.

PMID- 28751214
TI  - Glycan profiling analysis using evanescent-field fluorescence-assisted lectin
      array: Importance of sugar recognition for cellular uptake of exosomes from
      mesenchymal stem cells.
AB  - Studies involving the functional analysis of exosomal contents including
      proteins, DNA, and RNA have been reported. Most membrane proteins and lipids are
      glycosylated, which controls their physical properties and functions, but little
      is known about glycans on exosomes owing to the difficulty of analysing them. To
      shed light on these issues, we collected exosomes from mesenchymal stem cells
      (MSCs) derived from human adipose tissue for glycan profiling using evanescent
      field fluorescence-assisted lectin array as well as analysis of their uptake in
      vivo. Initial analyses showed that the mean diameter of the collected exosomes
      was 178 nm and they presented with typical exosomal and MSC markers. Regarding
      the glycan profiling, exosomes interacted more strongly than the membrane of the
      original MSCs did with a range of lectins, especially sialic acid-binding
      lectins. The findings also showed that cellular exosome uptake involved
      recognition by HeLa cell-surface-bound sialic acid-binding immunoglobulin (Ig)
      like lectins (siglecs). Confirming this siglec-related uptake, in vivo
      experiments involving subcutaneous injection of the fluorescently labelled
      exosomes into mice showed their transport into lymph nodes and internalization by
      antigen-presenting cells, particularly those expressing CD11b. Closer analysis
      revealed the colocalization of the exosomes with siglecs, indicating their
      involvement in the uptake. These findings provide us with an improved
      understanding of the importance of exosomal transport and targeting in relation
      to glycans on exosomal surfaces, potentially enabling us to standardize exosomes
      when using them for therapeutic purposes.

PMID- 28751215
TI  - Protective effects of 4-methylcoumarins and related compounds as radical
      scavengers and chain-breaking antioxidants.
AB  - The aim of this study is to determine, and to compare the protective effects of
      eight 4-methylcoumarins and four related compounds as radical scavengers and
      chain-breaking antioxidants. The main kinetic parameters of their radical
      scavenging activity (as % RSA, stoichiometry, n, and rate constants of reaction
      with DPPH radical, kRSA) and of chain breaking antioxidant activity (as
      antioxidant efficiency, PF and reactivity, ID), have been determined and
      discussed. The RSA study has been conducted at physiological temperature (37 
      degrees S) towards DPPH radical and the tested compounds are separated into three
      main groups: with strong activity (% RSA > 40%); with moderate activity (20% < %
      RSA > 40%) and with weak activity (% RSA < 20%). Chain-breaking antioxidant
      activities of the studied compounds have been evaluated during bulk phase lipid
      (triacylglycerols of sunflower oil, TGSO) autoxidation at 80  degrees C. All
      results obtained are compared with those for standard and known inhibitors of
      oxidation processes, e.g. caffeic and p-coumaric acids, alpha-tocopherol and
      butylated hydroxytoluene (BHT). On the basis of a comparative analysis with
      standard antioxidants, the differences in the radical scavenging and antioxidant
      abilities of the studied compounds have been discussed and reaction mechanisms
      proposed. All structures are optimized at UB3LYP/6-31 + G(d,p) level in gas phase
      and in acetone solution to study the solvation effects.

PMID- 28751216
TI  - Structural studies of amyloid-beta peptides: Unlocking the mechanism of
      aggregation and the associated toxicity.
AB  - Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases
      worldwide. Formation of amyloid plaques consisting of amyloid-beta peptides
      (Abeta) is one of the hallmarks of AD. Several lines of evidence have shown a
      correlation between the Abeta aggregation and the disease development. Extensive
      research has been conducted with the aim to reveal the structures of the
      neurotoxic Abeta aggregates. However, the exact structure of pathological
      aggregates and mechanism of the disease still remains elusive due to complexity
      of the occurring processes and instability of various disease-relevant Abeta
      species. In this article we review up-to-date structural knowledge about amyloid
      beta peptides, focusing on data acquired using solution and solid state NMR
      techniques. Furthermore, we discuss implications from these structural studies on
      the mechanisms of aggregation and neurotoxicity.

PMID- 28751217
TI  - Human placenta expresses both peripheral and neuronal isoform of tryptophan
      hydroxylase.
AB  - The role of placental serotonin has been an active topic of research notably
      because of its crucial role in brain development. However, which cell types
      synthesize serotonin in human placenta remains unknown. Moreover, it is not known
      if the two tryptophan hydroxylase isoforms (TPH1 and TPH2), the rate-limiting
      enzymes in serotonin biosynthesis, are expressed in placenta. Human placentas
      were obtained in first trimester or at term, and trophoblast cells were isolated
      and purified using a magnetic cell sorter and placed in primary culture. The
      tissue sublocalization of each TPH was determined by immunohistochemistry. TPH
      expression in primary villous trophoblasts was determined by PCR and
      immunoblotting, and serotonin secretion by LC-MS/MS. Villous cytotrophoblasts,
      syncytiotrophoblast, fetal capillaries, extravillous cytotrophoblasts, and
      decidual cells co-expressed TPH1 and TPH2. Moreover, mRNA and protein levels of
      both TPHs were detected in human primary trophoblast as well as in mouse
      placental tissues. Finally, human trophoblast cells were shown to produce
      serotonin de novo. This study demonstrates that both TPH1 and TPH2 are expressed
      in human and mouse placenta throughout pregnancy and helps to better understand
      the placental serotonin system, which is crucial for healthy pregnancy and fetal
      development. It is therefore important to further understand regulation of the
      placental serotonin system and how its disruption during pregnancy may impact the
      developing fetus and subsequent child programming.

PMID- 28751218
TI  - Brain lipoprotein lipase as a regulator of energy balance.
AB  - The central nervous system is an essential actor in the control of the energy
      balance. Indeed, many signals of nervous (vagal afferent for example) or
      circulating (hormone, nutrients) origin converge towards the brain to inform it
      permanently of the energetic status of the organism. In turn, the brain sends
      information to the periphery (sympathetic vagal balance, thyroid or corticotropic
      axis) which allows a fine regulation of the energy fluxes by acting on the
      hepatic glucose production, the secretion of the pancreatic hormones (glucagon,
      insulin) or food behavior. Among the nutrients, increasing amount of data assigns
      a signal molecule role to lipids such as fatty acids. These fatty acids may
      originate from the bloodstream but may also be the product of the hydrolysis of
      lipoproteins such as chylomicrons or VLDLs. Indeed, the identification of
      lipoprotein lipase (LPL) in the brain has led to the hypothesis that the LPL
      dependent degradation of TG-enriched particles, and the addition of fatty acids,
      as informative molecules, to sensitive cells (neurons and/or astrocytes), plays a
      key role in maintaining the energy balance at equilibrium. Other lipases could
      also participate in these regulatory mechanisms. This review will summarize the
      state of the art and open up perspectives.

PMID- 28751219
TI  - Structural studies with BnSP-7 reveal an atypical oligomeric conformation
      compared to phospholipases A2-like toxins.
AB  - There are 2.5 million cases of snakebite per year and approximately 100,000 to
      150,000 deaths. Thus, it is considered an important public health problem by the
      World Health Organization. Snakes from the Bothrops genus may cause severe local
      effects in the victims, so it is important to develop inhibitors to treat local
      effects in patients. In addition, approximately 30 different species of bothropic
      snakes have been described that may present differences in their venom
      composition. Small structural differences in the venom proteins may result in
      different ligands binding. Herein, BnSP-7, a PLA2-like protein that causes local
      myotoxic effects, was analyzed using different biophysical techniques. Crystal
      structures of BnSP-7 binding to three different cinnamic acid derivates were
      solved showing that the ligands bind in the membrane-dockage region (MDoS) of the
      protein. Spectroscopy fluorescence and microscale thermophoresis (MST) assays
      showed that these ligands also bind to BnSP-7 in solution and provide comparative
      information about their affinity to BnSP-7. MST experiments also showed that
      hydroxyl radicals of the ligands, involved in their binding with the MDoS region
      of BnSP-7, are essential to increase their affinity with the protein. As this
      region has been indicated as essential for the myotoxic mechanism, the ligands
      could potentially be used as inhibitors for BnSP-7. These results provide
      relevant insights to understand the PLA2-like proteins myotoxic mechanism and may
      eventually lead to design of new inhibitors for these toxins. Furthermore, a
      comparative structural analysis of BnSP-7 with other PLA2-like proteins showed
      that BnSP-7 has an atypical quaternary conformation, suggesting an intermediate
      state that is unlike other PLA2-like proteins. This information, combined with
      the absence or partial occupancy of molecules in their hydrophobic channel and
      the misaligned membrane-disruption region, led us to hypothesize that the protein
      is not able to fully exert its myotoxic activity like other PLA2-like proteins.

PMID- 28751220
TI  - The epicardium as a source of multipotent adult cardiac progenitor cells: Their
      origin, role and fate.
AB  - Since the regenerative capacity of the adult mammalian heart is limited, cardiac
      injury leads to the formation of scar tissue and thereby increases the risk of
      developing compensatory heart failure. Stem cell therapy is a promising
      therapeutic approach but is facing problems with engraftment and clinical
      feasibility. Targeting an endogenous stem cell population could circumvent these
      limitations. The epicardium, a membranous layer covering the outside of the
      myocardium, is an accessible cell population which plays a key role in the
      developing heart. Epicardial cells undergo epithelial to mesenchymal transition
      (EMT), thus providing epicardial derived cells (EPDCs) that migrate into the
      myocardium and cooperate in myocardial vascularisation and compaction. In the
      adult heart, injury activates the epicardium, and an embryonic-like response is
      observed which includes EMT and differentiation of the EPDCs into cardiac cell
      types. Furthermore, paracrine communication between the epicardium and myocardium
      improves the regenerative response. The significant role of the epicardium has
      been shown in both the developing and the regenerating heart. Interestingly, the
      epicardial contribution to cardiac repair can be improved in several ways. In
      this review, an overview of the epicardial origin and fate will be given and
      potential therapeutic approaches will be discussed.

PMID- 28751221
TI  - Labdane diterpenoids as potential anti-inflammatory agents.
AB  - The search for new anti-inflammatory agents is challenging due to the complexity
      of the inflammatory process and its role in host defense. Over the past few
      decades, a significant body of evidence has emerged, supporting the prominent
      role of labdane diterpenoids in therapeutic interventions of various inflammatory
      diseases. The anti-inflammatory activity of labdane diterpenoids has been
      attributed mainly to the inhibition of nuclear factor-kappaB (NF-kappaB)
      activity, the modulation of arachidonic acid (AA) metabolism and the reduction of
      nitric oxide (NO) production. This article provides extensive coverage of
      naturally occurring labdane diterpenes, discovered between 1981 and 2016, which
      have been verified as NF-kappaB, NO, or AA modulators. Herein, we also discuss
      the role of Michael acceptor, a common structural feature present in most of the
      active labdane diterpenes, and its association with NF-kappaB signaling
      inhibition. In the cases where a sufficient amount of data exists, structure
      activity relationship (SAR) studies and clinical studies performed on the anti
      inflammatory labdane diterpenoids are also discussed.

PMID- 28751222
TI  - The use of a composite synthetic mesh in the vicinity of bowel - For repair and
      prophylaxis of parastomal hernias. Does it increase the risk of short term
      infective complications?
AB  - AIMS: The use of synthetic meshes in potentially infected operative fields such
      as in the vicinity of large bowel, is controversial. This study describes our
      experience with the use of a synthetic composite mesh for prophylaxis and repair
      of parastomal hernias. METHODS: Data were collected retrospectively over a 7-year
      period from 2008 to 2015. An IPOM (DynaMeshTM) was used either during the
      formation of the stoma to reinforce the abdominal wall around the stoma or during
      the surgical repair of existing parastomal hernias, using keyhole or sandwich
      technique. Majority of meshes were placed laparoscopically. Clinical data and
      outcomes any stoma wound complications were collected. RESULTS: Forty seven
      patients were included with a male to female ratio of 34:13. Median age was 66
      years (38-91 years) with median follow-up of 17 months (3-73 months). Twenty
      seven patients had a prophylactic mesh placement (PMP) around colostomy after
      resection of colorectal cancer. None of these patients had any wound
      complications. Twenty patients had repair of parastomal hernias (RPH). One
      patient (1/20) in this group had a superficial wound infection around the stoma
      site and underwent an incision and drainage. One patient developed seroma and one
      had parastomal wound haematoma. CONCLUSIONS: The use of a composite synthetic
      mesh using a laparoscopic IPOM technique for the prophylaxis and treatment of
      parastomal hernias, even in a clean contaminated surgical field, is safe and
      feasible.

PMID- 28751223
TI  - Intra-abdominal infection after radical gastrectomy for gastric cancer:
      Incidence, pathogens, risk factors and outcomes.
AB  - BACKGROUND: Surgical site infection, particularly intra-abdominal infection
      (IAI), remains a clinically important event after gastrectomy for gastric cancer.
      The aim of this retrospective study was to clarify the incidence, pathogens, risk
      factors and outcomes of IAI following gastrectomy for gastric cancer. METHODS:
      The study cohort was 1835 patients who underwent gastrectomy for gastric cancer
      from January 2011 through December 2016. The incidence, pathogens, and treatment
      outcomes of IAI were examined, and the risk factors were identified using
      univariate and multivariate analyses. RESULTS: In total, 73 patients (4.0%)
      developed IAI after radical gastrectomy. Bacterial culture in these patients
      showed that Gram-negative bacilli, such as Escherichia coli and Klebsiella
      pneumonia were the most common pathogens. Multivariate analysis identified that
      combined multi-organ resection (Odds Ratio [OR] = 2.262, 95% confidence interval
      [CI]: 1.114-4.596, P = 0.024), and body mass index (BMI) >= 25 kg/m2 (OR = 1.968,
      95% CI: 1.107-3.500, P = 0.021) were independent risk factors. Three patients
      (4.1%) developed IAI who died from sepsis and/or multiple-organ failure, which
      was significantly higher than in the remaining 1762 patients without IAI (5
      cases, 0.3%, P = 0.003). Moreover, IAI required more re-operations (5.5% vs 0.8%,
      P = 0.005) and longer post-operative hospital stays (23.3 days vs 11.2 days, P <
      0.001) compared without IAI. CONCLUSIONS: IAI is a major complication after
      radical gastrectomy for gastric cancer, and associated with combined multi-organ
      resection and a BMI >= 25 kg/m2; thus, meticulous surgical procedures need to be
      performed in patients with these specific risk factors.

PMID- 28751224
TI  - Molecular cloning and functional characterization of eleven subtypes of
      interferon-alpha in Amur tigers (Panthera tigris altaica).
AB  - Interferon has a broad-spectrum of antiviral effects and represents an ideal
      choice for the development of antiviral drugs. Nonetheless, information about
      alpha interferon (IFN-alpha) is vacant in Amur tiger (Panthera tigris altaica),
      an endangered species and indigenous to northeast Asia. Herein, 11 PtIFN-alphas
      genes, which encoded proteins of 164-165 amino acids, were amplified. Afterwards,
      expression and purification were conducted in Escherichia coli. In
      physicochemical analysis, PtIFN-alphas were shown to be highly sensitive to
      trypsin and remained stable despite changes in pH and temperature. In feline
      kidney cells (F81)/vesicular stomatitis virus (VSV)/canine distemper virus
      (CDV)/avian influenza virus (AIV) systems, PtIFN-alphas were demonstrated to have
      distinct antiviral activities, some of them (PtIFN-alpha and PtIFN-alpha9)
      inhibited viral transcription levels more effectively than the other subtypes
      including Felis catus IFN-alpha, an effective therapeutic agent used for viral
      infections clinically. Additionally, PtIFN-alpha and PtIFN-alpha9 can up-regulate
      the transcription and expression of p53, a tumor suppressor factor, which could
      promote apoptosis of virus-infected cells. In conclusion, we cloned and expressed
      11 subtypes of PtIFN-alpha for the first time. Furthermore, PtIFN-alpha and PtIFN
      alpha9 were likely to be more efficient against both chronic viral infections and
      neoplastic diseases that affect the Amur tiger population. It will be of
      significant importance for further studies to protect this endangered species.

PMID- 28751225
TI  - Safety of transcranial direct current stimulation: Evidence based update 2016.

PMID- 28751226
TI  - BDNF Val66Met but not transcranial direct current stimulation affects motor
      learning after stroke.
AB  - BACKGROUND: tDCS is a non-invasive neuromodulation technique that has been
      reported to improve motor skill learning after stroke. However, the contribution
      of tDCS to motor skill learning has only been investigated in a small number of
      studies. In addition, it is unclear if tDCS effects are mediated by activity
      dependent BDNF release and dependent on timing of tDCS relative to training.
      OBJECTIVE: Investigate the role of activity-dependent BDNF release and timing of
      tDCS relative to training in motor skill learning. METHODS: Double-blind, between
      subjects randomized controlled trial of circuit tracing task improvement
      (DeltaMotor skill) in 80 chronic stroke patients who underwent tDCS and were
      genotyped for BDNF Val66Met. Patients received either short-lasting tDCS (20 min)
      during training (short-lasting online group), long-lasting tDCS (10 min-25 min
      break - 10 min) one day before training (long-lasting offline group), short
      lasting tDCS one day before training (short-lasting offline group), or sham tDCS.
      DeltaMotor skill was defined as the skill difference on the circuit tracing task
      between day one and day nine of the study. RESULTS: Having at least one BDNF Met
      allele was found to diminish DeltaMotor skill (betaBDNF,Met = -0.217 95%HDI = [
      0.431 -0.0116]), indicating activity-dependent BDNF release is important for
      motor skill learning after stroke. However, none of the tDCS protocols affected
      DeltaMotor skill (betaShort-lasting,online = 0.0908 95%HDI = [-0.227 0.403];
      betaLong-lasting,offline = 0.0242 95%HDI = [-0.292 0.349]; betaShort
      lasting,offline = -0.108 95%HDI = [-0.433 0.210]). CONCLUSION: BDNF Val66Met is a
      determinant of motor skill learning after stroke and could be important for
      prognostic models. tDCS does not modulate motor skill learning in our study and
      might be less effective than previously assumed.

PMID- 28751227
TI  - Postoperative local-regional radiation therapy in the treatment of parathyroid
      carcinoma: The MD Anderson experience of 35 years.
AB  - PURPOSE: We aimed to investigate outcomes of locoregional radiation therapy (XRT)
      in parathyroid carcinoma (PC) patients at a single institution over 35 years.
      METHODS AND MATERIALS: Retrospective review of PC patients who received
      postoperative locoregional XRT (1980-2015). Patients were grouped according to
      XRT after PC initial operation or after salvage surgery. All patients with a
      histopathological diagnosis of PC who had postoperative locoregional XRT at our
      institution were included. All patients with a histopathological diagnosis of
      uncertain malignancy, suggestive for malignancy, or atypical parathyroid tumors
      and those who had XRT outside our institution were excluded. RESULTS: Eight
      patients received XRT, 4 in each group, with a median follow-up of 12.5 years.
      The 4 patients who had XRT after initial surgery all had an oncologic operation,
      including ipsilateral thyroid lobectomy and central neck dissection, and all of
      these patients were disease-free at last follow-up. Of the 4 patients who
      received XRT after salvage surgery, only 1 remained disease free. There were no
      major complications/long-term side effects associated with XRT. CONCLUSIONS: XRT
      is well tolerated as postoperative locoregional treatment of patients with PC.
      Whether it is needed, and the timing of administering XRT, remains to be
      established.

PMID- 28751228
TI  - Consideration of patient and disease characteristics in selecting radiation
      regimens for treatment of bone metastases.
AB  - PURPOSE: Radiation therapy is one of the mainstays of treatment for painful bone
      metastases; however, the optimal fractionation and dosing of radiation for a
      given patient and disease characteristics are still subject to debate. METHODS
      AND MATERIALS: We retrospectively examined 475 patients who received radiation
      for bone metastases at our institution from 2009 through 2014 and evaluated
      survival outcomes based on parameters of their first treatment course and patient
      demographics. Kaplan-Meier analysis was used to analyze factors associated with
      overall survival (OS). A recursive partition analysis (RPA) was used to generate
      a decision tree of patient characteristics resulting in significant differences
      in survival. A Cox model was used to verify the RPA and evaluate the significance
      of biologically equivalent dose (BED) along with other factors. RESULTS: In our
      cohort, median age was 62 years and median Karnofsky performance status (KPS) was
      70. Survival time by primary tumor type: breast (median, 35.9 months), prostate
      (12.8 months), other (median, 11.0 months), lung (median, 5.3 months), and
      gastrointestinal (median, 4.0 months) (P < .0001). Primary tumor type and KPS
      significantly affected survival, whereas age was also significant for survival in
      certain primary tumor types. Pain control was not found to be significantly
      affected by primary tumor type (P = .72) or BED (P = .14). CONCLUSION: Our data
      demonstrate that selection of radiation fractionation schedules should take into
      account primary tumor type, KPS, and age, and we have generated an RPA model
      including these factors to help guide decision making. We also found that shorter
      fractionation schedules are as effective as longer fractionation schedules for
      pain control, regardless of primary tumor type.

PMID- 28751229
TI  - Improving efficiency and safety in external beam radiation therapy treatment
      delivery using a Kaizen approach.
AB  - INTRODUCTION: Modern external beam radiation therapy treatment delivery processes
      potentially increase the number of tasks to be performed by therapists and thus
      opportunities for errors, yet the need to treat a large number of patients daily
      requires a balanced allocation of time per treatment slot. The goal of this work
      was to streamline the underlying workflow in such time-interval constrained
      processes to enhance both execution efficiency and active safety surveillance
      using a Kaizen approach. METHODS AND MATERIALS: A Kaizen project was initiated by
      mapping the workflow within each treatment slot for 3 Varian TrueBeam linear
      accelerators. More than 90 steps were identified, and average execution times for
      each were measured. The time-consuming steps were stratified into a 2 * 2 matrix
      arranged by potential workflow improvement versus the level of corrective effort
      required. A work plan was created to launch initiatives with high potential for
      workflow improvement but modest effort to implement. Time spent on safety
      surveillance and average durations of treatment slots were used to assess
      corresponding workflow improvements. RESULTS: Three initiatives were implemented
      to mitigate unnecessary therapist motion, overprocessing of data, and wait time
      for data transfer defects, respectively. A fourth initiative was implemented to
      make the division of labor by treating therapists as well as peer review more
      explicit. The average duration of treatment slots reduced by 6.7% in the 9 months
      following implementation of the initiatives (P = .001). A reduction of 21% in
      duration of treatment slots was observed on 1 of the machines (P < .001). Time
      spent on safety reviews remained the same (20% of the allocated interval), but
      the peer review component increased. CONCLUSIONS: The Kaizen approach has the
      potential to improve operational efficiency and safety with quick turnaround in
      radiation therapy practice by addressing non-value-adding steps characteristic of
      individual department workflows. Higher effort opportunities are identified to
      guide continual downstream quality improvements.

PMID- 28751230
TI  - Dose de-escalation to the elective lymph nodes in head and neck cancer. Reply to
      Amdur et al.

PMID- 28751231
TI  - Concurrent administration of anti-HER2 therapy and radiotherapy: Systematic
      review.
AB  - BACKGROUND: Over the past few years, anti-HER2 targeted therapies have proven to
      be a key treatment in the management of human epidermal growth receptor 2 (HER2)
      positive breast cancers, as well as gastrointestinal tract tumors and head and
      neck tumors. Anti-HER2 therapies administered alone or in combination with
      chemotherapy have been extensively studied, but only limited robust data are
      available concerning the safety and efficacy of anti-HER2 molecules in
      combination with radiotherapy. METHODS: We searched on Medline, Embase and
      Cochrane databases the articles providing data on the concomitant association
      between the antiHER2 therapies used in clinical practice (trastuzumab,
      pertuzumab, lapatinib and T-DM1) with radiotherapy. The articles were selected
      according to their pre-clinical and clinical relevance. RESULTS: The trastuzumab
      irradiation combination is the most studied, with a focus on the cardiac
      toxicity. The combination of lapatinib-irradiation was particularly studied in
      the context of cerebral metastases of HER2-positive breast cancer. The data on
      pertuzumab and T-DM1 were poor and are mainly case reports. CONCLUSION: To date,
      reliable conclusions about the toxicity and/or efficacy of concomitant
      irradiation with anti-HER2 therapies are difficult to make due to the
      heterogeneity of the data in the literature and need to be confirmed on a larger
      scale and long term follow-up. Nevertheless, no serious adverse events are
      reported and the toxicity profile seems to be manageable.

PMID- 28751232
TI  - Omalizumab treatment in patients with chronic inducible urticaria: A systematic
      review of published evidence.
AB  - BACKGROUND: Omalizumab, a recombinant anti-IgE antibody, effectively treats
      chronic spontaneous urticaria. Evidence is lacking in patients with chronic
      inducible urticarias (CIndUs), which are frequently H1-antihistamine resistant.
      OBJECTIVE: From the current published literature, we aimed to determine the
      strength of evidence for omalizumab efficacy and safety in the treatment of
      CIndUs. METHODS: We performed a PubMed search to identify evidence on omalizumab
      use in the following 9 CIndU subtypes: symptomatic dermographism, cold urticaria,
      delayed-pressure urticaria, solar urticaria, heat urticaria, vibratory
      angioedema, cholinergic urticaria, contact urticaria, and aquagenic urticaria.
      RESULTS: Forty-three trials, case studies, case reports, and analyses were
      identified. Our review indicates that omalizumab has substantial benefits in
      patients with various CIndUs. The evidence is strongest for symptomatic
      dermographism, cold urticaria, and solar urticaria. Little/no evidence was
      available on vibratory angioedema and aquagenic and contact urticaria. Our review
      supports rapid onset of action demonstrated through early symptom control in most
      cases, sometimes within 24 hours. Many patients gained complete/partial symptom
      relief and substantially improved quality of life. Adverse events were generally
      low, with omalizumab being well tolerated by most patients, including children.
      CONCLUSIONS: A strong body of evidence supports the use of omalizumab in the
      treatment of patients with therapy-refractory CIndU. More data from randomized
      controlled studies are warranted.

PMID- 28751233
TI  - Sputum autoantibodies in patients with severe eosinophilic asthma.
AB  - BACKGROUND: The persistence of eosinophils in sputum despite high doses of
      corticosteroids indicates disease severity in asthmatic patients. Chronic
      inflamed airways can lose tolerance over time to immunogenic entities released on
      frequent eosinophil degranulation, which further contributes to disease severity
      and necessitates an increase in maintenance corticosteroids. OBJECTIVES: We
      sought to investigate the possibility of a polyclonal autoimmune event in the
      airways of asthmatic patients and to identify associated clinical and molecular
      characteristics. METHODS: The presence of autoantibodies against eosinophil
      peroxidase (EPX) and anti-nuclear antibodies was investigated in patients with
      eosinophilic asthma maintained on high-dose corticosteroids, prednisone, or both.
      The ability of sputum immunoglobulins to induce eosinophil degranulation in vitro
      was assessed. In addition, the associated inflammatory microenvironment in
      patients with detectable autoantibodies was examined. RESULTS: We report a
      "polyclonal" autoimmune event occurring in the airways of prednisone-dependent
      asthmatic patients with increased eosinophil activity, recurrent pulmonary
      infections, or both, as evident by the concomitant presence of sputum anti-EPX
      and anti-nuclear antibodies of the IgG subtype. Extensive cytokine profiling of
      sputum revealed a TH2-dominated microenvironment (eotaxin-2, IL-5, IL-18, and IL
      13) and increased signalling molecules that support the formation of ectopic
      lymphoid structures (B-cell activating factor and B cell-attracting chemokine 1).
      Immunoprecipitated sputum immunoglobulins from patients with increased
      autoantibody levels triggered eosinophil degranulation in vitro, with release of
      extensive histone-rich extracellular traps, an event unsuppressed by
      dexamethasone and possibly contributing to the steroid-unresponsive nature of
      these eosinophilic patients. CONCLUSION: This study identifies an autoimmune
      endotype of severe asthma that can be identified by the presence of sputum
      autoantibodies against EPX and autologous cellular components.

PMID- 28751234
TI  - Hysteroscopic Treatment of a Uterine Cystic Adenomyosis.

PMID- 28751235
TI  - Laparoscopic Uterovaginal Anastomosis for Cervical Agenesis: A Case Report.
AB  - STUDY OBJECTIVE: Isolated cervical agenesis occurs in 1 in 80 000 to 100 000
      births. According to the American Fertility Society, cervical agenesis should be
      classified as a type Ib mullerian anomaly. According to ESHRE/ESGE
      classification, it is classified in class C4 category. Here we demonstrate the
      possibility of an innovative surgery for the management of cervical agenesis.
      DESIGN: Stepwise description of laparoscopic uterovaginal anastomosis (Canadian
      Task Force classification II-3). SETTING: Video. PATIENT: A 13-year-old girl.
      INTERVENTION: Laparoscopic uterovaginal anastomosis was performed. Informed
      consent was taken from the patient for use of video and images. Institutional
      review board has ruled that approval was not required for this study.
      MEASUREMENTS AND MAIN RESULTS: This video demonstrates the management of a case
      of a 13-year-old girl with primary amenorrhea and cyclical lower abdominal pain
      for 5 months. After complete examination and investigation, a diagnosis of
      isolated cervical agenesis with hematomata and blind-ending vagina was made. An
      innovative technique was used to perform laparoscopic uterovaginal anastomosis.
      Later, a hysteroscopy was done that revealed patency of anastomoses. As a result,
      the patient is experiencing spontaneous regular menstruation for 48 months. The
      main steps of the procedure were as follows: A follow-up hysteroscopy was
      performed at 9 weeks after surgery. It showed patent anastomosis and normal
      uterine cavity. After 48 months, a repeat hysteroscopy was done and a partial
      fibrotic septum noted. It was resected using electric energy. CONCLUSION:
      Uterovaginal anastomosis for isolated cervical agenesis is possible by a
      minimally invasive approach. It can be offered as a first-line management for
      such cases over hysterectomy and cervical canalization, which have high
      complication rates. The surgery should only be performed by a specialized team
      with required expertise in minimally invasive surgery.

PMID- 28751236
TI  - Binding of bisphenol A, bisphenol AF, and bisphenol S on the androgen receptor:
      Coregulator recruitment and stimulation of potential interaction sites.
AB  - Bisphenol A (BPA), bisphenol AF (BPAF), and bisphenol S (BPS) are well known
      endocrine disruptors. Previous in vitro studies showed that these compounds
      antagonize androgen receptor (AR) transcriptional activity; however, the
      mechanisms of action are unclear. In the present study, we investigated
      interactions of coregulator peptides with BPA, BPAF, or BPS at the AR complexes
      using Micro Array for Real-time Coregulator Nuclear Receptor Interaction
      (MARCoNI) assays and assessed the binding of these compounds on AR by molecular
      dynamics (MD) simulations. The set of coregulator peptides that are recruited by
      BPA-bound AR, either positively/or negatively, are different from those recruited
      by the agonist R1881-bound AR. Therefore, the data indicates that BPA shows no
      similarities to R1881 and suggests that it may recruit other coregulators to the
      AR complex. BPAF-bound AR recruits about 70-80% of the same coregulator peptides
      as BPA-bound AR. Meanwhile, BPS-bound AR interacts with only few peptides
      compared to BPA or BPAF-bound AR. MD results show that multiple binding sites
      with varying binding affinities are available on AR for BPA, BPAF, and BPS,
      indicating the availability of modified binding surfaces on AR for coregulator
      interactions. These findings help explain some of the distinct AR-related
      toxicities observed with bisphenol chemicals and raise concern for the use of
      substitutes for BPA in commercial products.

PMID- 28751237
TI  - A large modern Southeast Asian human skeletal collection from Thailand.
AB  - The Khon Kaen University Human Skeleton Research Centre has a large human
      collection consisting of 745 modern northeastern Thai (Isan) skeletons derived
      from bodies bequeathed to the Department of Anatomy during the period 1979-2014.
      The aim of this paper is to document the collection and address the question of
      whether the collection may be representative of local Isan people, or populations
      of the wider region of mainland Southeast Asia. This will determine its value as
      a reference collection for forensic anthropology in particular but also for all
      other fields of research about human skeletal biology. Sex is recorded for 99.6%
      of the skeletons, and age at death for 91.7%. The collection consists of two
      thirds males, one-third females. It includes 10 individuals less than 19 years of
      age, and adults ranging in age from 20 to 109 years of age. Average age at death
      is 62 years. Other data available for smaller proportions of the collection
      include cause of death, occupation, and height and weight at the time of
      donation. Dates of birth are estimated to range from the late 19th Century to the
      most recent in 1988. Analysis of the demographic composition of the collection
      shows that is likely to be representative of the ancestral mix of the Isan
      people, and of the village farmers who still form a large portion of the Isan
      population. It may also represent 20th Century populations of much of Southeast
      Asia where agriculture dominates the economy. The collection forms a valuable
      resource for research on regional human skeletal characteristics for use in
      forensic anthropology.

PMID- 28751240
TI  - Evaluation of vancomycin MIC creep in Staphylococcus aureus.
AB  - OBJECTIVES: Vancomycin is the primary treatment for methicillin-resistant
      Staphylococcus aureus (MRSA). However, an increasing proportion of MRSA isolates
      with high minimum inhibitory concentrations (MICs) within the susceptible range
      (vancomycin 'MIC creep') is being observed. The aim of this study was to assess
      the vancomycin MIC distribution for S. aureus isolates over a period of 4 years
      in Centro Hospitalar Baixo Vouga (Aveiro, Portugal) and to identify differences
      in vancomycin MIC determined by different susceptibility testing methods.
      METHODS: For each S. aureus isolate, the vancomycin MIC was assayed by the
      VITEK(r)2 automated system and the broth microdilution testing method. RESULTS:
      The results showed significant differences in vancomycin MIC by different methods
      (P=0.021, sign test) and did not suggest the presence of vancomycin MIC creep
      during the study period. CONCLUSIONS: Vancomycin MIC creep is a regional problem,
      therefore it can only be assessed through the evaluation of local susceptibility
      profiles, and antibiogram based on real MIC assay should be an essential element
      in local MRSA infection clinical management.

PMID- 28751239
TI  - Experiencing early life maternal separation increases pain sensitivity in adult
      offspring.
AB  - Maternal separation is a widely accepted model for studying long-term behavioral
      changes produced by events during early life and its association with changes in
      pain sensitivity. Thus, our objective was to evaluate sensitivity to pain, under
      different stimuli in adult male and female rats that had undergone early life
      maternal separation. Animals were subjected to maternal separation from postnatal
      day (PND) 2-15. Maternal behavior and litter weight were evaluated during this
      period. Sensitivity to pain was assessed in offsprings during adulthood by
      exposing them to stimuli, including formalin (5%; 20MUl), a hot plate, and the
      electronic von Frey test, 4, 7, 10, and 24h after the administration of saline or
      Freund's complete adjuvant (CFA) injection. Maternal separation did not affect
      maternal behavior or litter weight during PND 2-15. However, experiencing
      maternal separation increased pain sensitivity in the rats subjected to formalin
      by increasing number of flinches and licking time Further, females appeared more
      sensitive than males to thermal stimuli, as they showed a decrease in latency in
      the hot plate test. In this test, male and female offsprings that were exposed to
      early life maternal separation and received the CFA injection also showed a
      reduction in latency to react to the painful stimuli. In the von Frey test, there
      was a reduction in withdrawal threshold in maternal separation animals injected
      with CFA, thus demonstrating a greater sensitivity to the mechanical stimuli. In
      conclusion, experiencing early life maternal separation increased pain
      sensitivity in adult offsprings. Thus, our data are important to understand the
      impact of environmental influences, such as stressful life events during critical
      developmental periods, on pain vulnerability.

PMID- 28751238
TI  - bHLH proneural genes as cell fate determinants of entero-endocrine cells, an
      evolutionarily conserved lineage sharing a common root with sensory neurons.
AB  - Entero-endocrine cells involved in the regulation of digestive function form a
      large and diverse cell population within the intestinal epithelium of all
      animals. Together with absorptive enterocytes and secretory gland cells, entero
      endocrine cells are generated by the embryonic endoderm and, in the mature
      animal, from a pool of endoderm derived, self-renewing stem cells. Entero
      endocrine cells share many structural/functional and developmental properties
      with sensory neurons, which hints at the possibility of an ancient evolutionary
      relationship between these two cell types. We will survey in this article recent
      findings that emphasize the similarities between entero-endocrine cells and
      sensory neurons in vertebrates and insects, for which a substantial volume of
      data pertaining to the entero-endocrine system has been compiled. We will then
      report new findings that shed light on the specification and morphogenesis of
      entero-endocrine cells in Drosophila. In this system, presumptive intestinal stem
      cells (pISCs), generated during early metamorphosis, undergo several rounds of
      mitosis that produce the endocrine cells and stem cells (ISCs) with which the fly
      is born. Clonal analysis demonstrated that individual pISCs can give rise to
      endocrine cells expressing different types of peptides. Immature endocrine cells
      start out as unpolarized cells located basally of the gut epithelium; they each
      extend an apical process into the epithelium which establishes a junctional
      complex and apical membrane specializations contacting the lumen of the gut.
      Finally, we show that the Drosophila homolog of ngn3, a bHLH gene that defines
      the entero-endocrine lineage in mammals, is expressed and required for the
      differentiation of this cell type in the fly gut.

PMID- 28751241
TI  - Flexibility assessment of the unfused thoracic segments above the "potential
      upper instrumented vertebrae" using the supine side bending radiographs in Lenke
      5 and 6 curves for adolescent idiopathic scoliosis patients.
AB  - BACKGROUND CONTEXT: Selection of upper instrumented vertebra for Lenke 5 and 6
      curves remains debatable, and several authors have described different selection
      strategies. OBJECTIVE: This study analyzed the flexibility of the unfused
      thoracic segments above the "potential upper instrumented vertebrae (UIV)" (T1
      T12) and its compensatory ability in Lenke 5 and 6 curves using supine side
      bending (SSB) radiographs. STUDY DESIGN: A retrospective study was used. PATIENT
      SAMPLE: This study comprised 100 patients. OUTCOME MEASURES: The ability of the
      unfused thoracic segments above the potential UIV, that is, T1-T12, to compensate
      in Lenke 5 and 6 curves was determined. We also analyzed postoperative
      radiological outcome of this cohort of patients with a minimum follow-up of 12
      months. METHODS: Right and left SSB were obtained. Right side bending (RSB) and
      left side bending (LSB) angles were measured from T1 to T12. Compensatory ability
      of thoracic segments was defined as the ability to return to neutral (center
      sacral vertical line [CSVL]) with the assumption of maximal correction of lumbar
      curve with a horizontal UIV. The Lenke 5 curves were classified as follows: (1)
      Lenke 5-ve (mobile): main thoracic Cobb angle <15 degrees  and (2) Lenke 5+ve
      (stiff): main thoracic Cobb angle 15.0 degrees -24.9 degrees . This study was
      self-funded with no conflict of interest. RESULTS: There were 43 Lenke 5-ve, 31
      Lenke 5+ve, and 26 Lenke 6 curves analyzed. For Lenke 5-ve, >70% of thoracic
      segments were able to compensate when UIV were at T1-T8 and T12 and >50% at T9
      T11. For Lenke 5+ve, >70% at T1-T6 and T12, 61.3% at T7, 38.7% at T8, 3.2% at T9,
      6.5% at T10, and 22.6% at T11 were able to compensate. For Lenke 6 curve, >70% at
      T1-T6, 69.2% at T7, 19.2% at T8, 7.7% at T9, 0% at T10, 3.8% at T11, and 34.6% at
      T12 were able to compensate. There was a significant difference between Lenke 5
      ve versus Lenke 5+ve and Lenke 5-ve versus Lenke 6 from T8 to T11. There were no
      significance differences between Lenke 5+ve and Lenke 6 curves from T1 to T11.
      CONCLUSIONS: The compensatory ability of the unfused thoracic segment of Lenke
      5+ve curves was different from the Lenke 5-ve curves, and it demonstrated
      characteristics similar to the Lenke 6 curves.

PMID- 28751242
TI  - Evaluation of a polyetheretherketone (PEEK) titanium composite interbody spacer
      in an ovine lumbar interbody fusion model: biomechanical, microcomputed
      tomographic, and histologic analyses.
AB  - BACKGROUND CONTEXT: The most commonly used materials used for interbody cages are
      titanium metal and polymer polyetheretherketone (PEEK). Both of these materials
      have demonstrated good biocompatibility. A major disadvantage associated with
      solid titanium cages is their radiopacity, limiting the postoperative monitoring
      of spinal fusion via standard imaging modalities. However, PEEK is radiolucent,
      allowing for a temporal assessment of the fusion mass by clinicians. On the other
      hand, PEEK is hydrophobic, which can limit bony ingrowth. Although both PEEK and
      titanium have demonstrated clinical success in obtaining a solid spinal fusion,
      innovations are being developed to improve fusion rates and to create stronger
      constructs using hybrid additive manufacturing approaches by incorporating both
      materials into a single interbody device. PURPOSE: The purpose of this study was
      to examine the interbody fusion characteristic of a PEEK Titanium Composite (PTC)
      cage for use in lumbar fusion. STUDY DESIGN/SETTING: Thirty-four mature female
      sheep underwent two-level (L2-L3 and L4-L5) interbody fusion using either a PEEK
      or a PTC cage (one of each per animal). Animals were sacrificed at 0, 8, 12, and
      18 weeks post surgery. MATERIALS AND METHODS: Post sacrifice, each surgically
      treated functional spinal unit underwent non-destructive kinematic testing,
      microcomputed tomography scanning, and histomorphometric analyses. RESULTS:
      Relative to the standard PEEK cages, the PTC constructs demonstrated significant
      reductions in ranges of motion and a significant increase in stiffness. These
      biomechanical findings were reinforced by the presence of significantly more bone
      at the fusion site as well as ingrowth into the porous end plates. CONCLUSIONS:
      Overall, the results indicate that PTC interbody devices could potentially lead
      to a more robust intervertebral fusion relative to a standard PEEK device in a
      clinical setting.

PMID- 28751243
TI  - Changes in protein abundance and activity induced by drought during generative
      development of winter barley (Hordeum vulgare L.).
AB  - : The present study investigated drought-induced changes in proteome profiles of
      ten DH lines of winter barley, relatively varied in water deficit tolerance
      level. Additionally, the parameters describing the functioning of the
      photosynthetic apparatus and the activity of the antioxidative system were
      analysed. Water deficit (3-week growth in soil with water content reduced to ca.
      35%) induced significant changes in leaf water relations and reduced
      photosynthetic activity, probably due to decreased stomatal conductance. It was
      associated with changes in protein abundance and altered activity of
      antioxidative enzymes. From 47 MS-identified proteins discriminating more
      tolerant from drought-sensitive genotypes, only two revealed distinctly higher
      while seven revealed lower abundance in drought-treated plants of tolerant DH
      lines in comparison to sensitive ones. The majority were involved in the dark
      phase of photosynthesis. Another factor of great importance seems to be the
      ability to sustain, during drought stress, relatively high activity of enzymes
      (SOD and CAT) decomposing reactive oxygen species and protecting plant cell from
      oxidative damages. Low molecular weight antioxidants seem to play less important
      roles. Our findings also suggest that high tolerance to drought stress in barley
      is a constitutively controlled trait regulated by the rate of protein synthesis
      and their activity level. BIOLOGICAL SIGNIFICANCE: According to our knowledge,
      this is the first comparative proteomic analysis of drought tolerance performed
      for the model set of several winter barley doubled haploid (DH) lines. We
      analysed both the drought impact on the protein pattern of individual winter
      barley DH lines as well as comparisons between them according to their level of
      drought tolerance. We have identified 47 proteins discriminating drought-tolerant
      from drought-sensitive genotypes. The majority was involved in the dark phase of
      photosynthesis. Another factor of great importance in our opinion seems to be the
      ability to sustain, during drought stress, relatively high activity of
      antioxidative enzymes (SOD and CAT) decomposing reactive oxygen species and
      protecting plant cell from oxidative damages. Our findings also suggest that high
      tolerance to drought stress in barley is a constitutively-controlled trait
      regulated by the rate of protein synthesis and their activity level.

PMID- 28751244
TI  - Cost-Effectiveness Analysis of Afatinib versus Gefitinib for First-Line Treatment
      of Advanced EGFR-Mutated Advanced Non-Small Cell Lung Cancers.
AB  - INTRODUCTION: The irreversible ErbB family blocker afatinib and the reversible
      EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter,
      international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line
      treatment of advanced EGFR mutation-positive NSCLCs. Afatinib and gefitinib costs
      and patients' outcomes in France were assessed. METHODS: A partitioned survival
      model was designed to assess the cost-effectiveness of afatinib versus gefitinib
      for EGFR mutation-positive NSCLCs. Outcomes and safety were taken primarily from
      the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an
      expert-panel questionnaire, and published literature, limiting expenditures to
      direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over
      a 10-year time horizon for the entire population, and EGFR exon 19 deletion or
      exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic
      sensitivity analyses were conducted. RESULTS: For all EGFR mutation-positive
      NSCLCs, the afatinib-versus-gefitinib ICER of was ?45,211 per quality-adjusted
      life-year (QALY) (0.170 QALY gain for an incremental cost of ?7697). ICERs for
      EGFR exon 19 deletion and L858R populations were ?38,970 and ?52,518,
      respectively. Afatinib had 100% probability to be cost-effective at a willingness
      to-pay threshold of ?70,000/QALY for patients with common EGFR mutations.
      CONCLUSION: First-line afatinib appears cost-effective compared with gefitinib
      for patients with EGFR mutation-positive NSCLCs.

PMID- 28751245
TI  - Comparison of 22C3 PD-L1 Expression between Surgically Resected Specimens and
      Paired Tissue Microarrays in Non-Small Cell Lung Cancer.
AB  - INTRODUCTION: The extent to which intratumoral heterogeneity of programmed death
      ligand 1 (PD-L1) expression causes discordance of PD-L1 expression between paired
      samples remains unclear. Here, PD-L1 status was compared between whole sections
      from NSCLCs and the corresponding tissue microarrays (TMAs) serving as surrogate
      biopsy specimens. METHODS: PD-L1 expression was evaluated by 22C3
      immunohistochemistry assay on 190 archival surgical specimens and matched to the
      TMA results. PD-L1 expression was determined by the tumor proportion score (TPS)
      and classified as TPS lower than 1%, TPS of 1% to 49%, and TPS of 50% or higher.
      Agreement statistics were used. RESULTS: The percentage of PD-L1 expression on
      tumor cells differed greatly between individual TMAs and matched surgical
      specimens. When PD-L1 TPS was adopted, a total of 36 of 190 discordance cases
      (18.9%) were observed, with a kappa-value of 0.630 between paired samples. The
      TMAs underestimated or overestimated PD-L1 status in 19 of 36 (52.8%) and 17 of
      36 (47.2%) of the matched surgical specimens, respectively (p = 0.118). The
      discordance rate was much lower in cases with a PD-L1 TPS lower than 1% compared
      with in cases with a TPS of 1% to 49% and TPS of 50% or higher (18.4% versus
      56.7% and 43.3%, p < 0.001). When a TPS of 50% or higher was used as the cutoff,
      the discordance rate of PD-L1 TPS less than 50% was further reduced to 7.5%. Such
      discrepancies were due mainly to intratumoral heterogeneity of PD-L1 expression
      and nonsignificant association with clinicopathological features. CONCLUSIONS: PD
      L1 expression in TMAs correlates moderately well with that in the corresponding
      surgical specimens, indicating that evaluating PD-L1 expression in diagnostic
      biopsy specimens could be misleading in defining sensitivity to pembrolizumab
      treatment yet may be reliable as a way to exclude patients with a PD-L1 TPS less
      than 50% from first-line pembrolizumab treatment.

PMID- 28751246
TI  - Concordance between Comprehensive Cancer Genome Profiling in Plasma and Tumor
      Specimens.
AB  - INTRODUCTION: Detection of somatic genomic alterations in the plasma of patients
      with cancer ("liquid biopsy") are increasingly being used in the clinic. However,
      the concordance of alterations identified in liquid biopsies with those detected
      in cancer specimens is not routinely being determined. METHODS: We sought to
      systematically compare alterations found by a massively parallel sequencing
      liquid biopsy assay covering 39 genes (NEOliquid [NEO New Oncology GmbH, Koln,
      Germany]) with those identified through routine diagnostic testing in a certified
      central pathology laboratory in a cohort of patients with nonsquamous NSCLC.
      NEOliquid is based on enrichment of the genomic territory of interest by hybrid
      capture and is thus capable of detecting point mutations, small insertions and
      deletions, copy number alterations, and gene rearrangements/fusions in a single
      assay. RESULTS: In a cohort of 82 patients with matched blood/tissue samples, the
      concordance between NEOliquid and tissue-based routine testing was 98%, the
      sensitivity of NEOliquid was higher than 70%, and the specificity was 100%.
      Discordant cases included those with insufficient amounts of circulaating tumor
      DNA in plasma and cases in which known driver mutations (e.g., isocitrate
      dehydrogenase (NADP(+)), 1 systolic gene [IDH1] R132H, kinesin family member 5B
      gene [KIF5b-ret proto-oncogene [RET], or MNNG HOS Transforming gene [MET] exon
      14) were found in the plasma but were not interrogated by routine tissue
      analyses. CONCLUSIONS: In summary, NEOliquid offers accurate and reliable
      detection of clinically relevant driver alterations in plasma of patients with
      cancer.

PMID- 28751247
TI  - Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor
      Biopsy Cohorts of the AURA Phase I Trial.
AB  - INTRODUCTION: Osimertinib is an oral, potent, irreversible EGFR tyrosine kinase
      inhibitor (TKI) selective for EGFR TKI and T790M resistance mutations. To enhance
      understanding of osimertinib's mechanism of action, we aimed to evaluate the
      modulation of key molecular biomarkers after osimertinib treatment in paired
      clinical samples from the phase I AURA trial. METHODS: Paired tumor biopsy
      samples were collected before the study and after 15 plus or minus 7 days of
      osimertinib treatment (80 or 160 mg daily). Clinical efficacy outcomes were
      assessed according to whether viable paired biopsy samples could be collected;
      safety was also assessed. Immunohistochemical analyses assessed key pathway and
      tumor/immune-relevant markers (phospho-EGFR, phospho-S6, phospho-AKT, programmed
      death ligand 1, and CD8), with samples scored by image analysis or a pathologist
      blinded to treatment allocation. RESULTS: Predose tumor biopsy samples were
      collected from 61 patients with EGFR T790M tumors; 29 patients had no viable
      postdose biopsy sample because of tumor regression or insufficient tumor sample.
      Evaluable predose and postdose tumor biopsy samples were collected from 24
      patients. Objective response rate (ORR) and median progression-free survival
      (mPFS) were improved in patients from whom a postdose biopsy sample could not be
      collected (ORR 62% and mPFS 9.7 months [p = 0.027]) compared with those from whom
      paired samples were collected (ORR 29% and mPFS 6.6 months). Osimertinib
      modulated key EGFR signaling pathways and led to increased immune cell
      infiltration. CONCLUSIONS: Collection of paired biopsy samples was challenging
      because of rapid tumor regression after osimertinib treatment, highlighting the
      difficulties of performing on-study biopsies in patients treated with highly
      active drugs.

PMID- 28751248
TI  - Reshapable polymeric hydrogel for controlled soft-tissue expansion: In vitro and
      in vivo evaluation.
AB  - Tissue expansion is the process by which extra skin is generated using a device
      that applies pressure from underneath the skin. Over the course of weeks to
      months, stretching by this pressure creates a flap of extra tissue that can be
      used to cover a defect area or enclose a permanent implant. Conventional tissue
      expanders require a silicone shell inflated either by external injections of
      saline solution or air, or by internal osmotic pressure generated by a
      hydrophilic polymer. In this study, a shell-free tissue expander comprised only
      of a chemically cross-linked biocompatible polymeric hydrogel is developed. The
      cross-linked network of hydrophilic polymer provides for intrinsically controlled
      swelling in the absence of an external membrane. The new type of hydrogel
      expanders were characterized in vitro as well as in vivo using a rat-skin animal
      model. It was found that increasing the hydrophobic polyester content in the
      hydrogel reduced the swelling velocity to a rate and volume that eliminate the
      danger of premature swelling rupturing the sutured area. Additionally, increasing
      the crosslinking density resulted in enough mechanical strength of the hydrogel
      to allow for complete post-swelling removal, without the hydrogel cracking or
      crumbling. No systemic toxicity was noted with the expanders and histology showed
      the material to be highly biocompatible. These expanders have an advantage of
      tissue expansion without requiring an external silicone membrane, and thus, they
      can be cut or reshaped at the time of implantation for applications in small or
      physically constrained regions of the body.

PMID- 28751249
TI  - delta-Protocadherins: Organizers of neural circuit assembly.
AB  - The delta-protocadherins comprise a small family of homophilic cell adhesion
      molecules within the larger cadherin superfamily. They are essential for neural
      development as mutations in these molecules give rise to human neurodevelopmental
      disorders, such as schizophrenia and epilepsy, and result in behavioral defects
      in animal models. Despite their importance to neural development, a detailed
      understanding of their mechanisms and the ways in which their loss leads to
      changes in neural function is lacking. However, recent results have begun to
      reveal roles for the delta-protocadherins in both regulation of neurogenesis and
      lineage-dependent circuit assembly, as well as in contact-dependent motility and
      selective axon fasciculation. These evolutionarily conserved mechanisms could
      have a profound impact on the robust assembly of the vertebrate nervous system.
      Future work should be focused on unraveling the molecular mechanisms of the delta
      protocadherins and understanding how this family functions broadly to regulate
      neural development.

PMID- 28751250
TI  - Wound redox gradients revisited.
AB  - Evidence emerges that redox gradients regulate morphogenesis, inflammation,
      regeneration, and healing of tissues. At the example of redox signaling during
      the zebrafish wound response, I briefly discuss current ideas on how such
      patterns might be sensed and spatially regulated to guide physiological processes
      over distances in animals.

PMID- 28751251
TI  - Autocrine mechanisms of cancer chemoresistance.
AB  - An ever-increasing number of studies highlight the role of cancer secretome in
      the modification of tumour microenvironment and in the acquisition of cancer cell
      resistance to therapeutic drugs. The knowledge of the mechanisms underlying the
      relationship between cancer cell-secreted factors and chemoresistance is becoming
      fundamental for the identification of novel anticancer therapeutic strategies
      overcoming drug resistance and novel prognostic secreted biomarkers. In this
      review, we summarize the novel findings concerning the regulation of secreted
      molecules by cancer cells compromising drug sensitivity. In particular, we
      highlight data from available literature describing the involvement of cancer
      cell-secreted molecules determining chemoresistance in an autocrine manner,
      including: i) growth factors; ii) glycoproteins; iii) inflammatory cytokines; iv)
      enzymes and chaperones; and v) tumor-derived exosomes.

PMID- 28751252
TI  - Pore-forming toxins in Cnidaria.
AB  - The ancient phylum of Cnidaria contains many aquatic species with peculiar
      lifestyle. In order to survive, these organisms have evolved attack and defense
      mechanisms that are enabled by specialized cells and highly developed venoms.
      Pore-forming toxins are an important part of their venomous arsenal. Along some
      other types, the most representative are examples of four protein families that
      are commonly found in other kingdoms of life: actinoporins, Cry-like proteins,
      aerolysin-like toxins and MACPF/CDC toxins. Some of the homologues of pore
      forming toxins may serve other functions, such as in food digestion, development
      and response against pathogenic organisms. Due to their interesting physico
      chemical properties, the cnidarian pore-forming toxins may also serve as tools in
      medical research and nanobiotechnological applications.

PMID- 28751253
TI  - Molecular mechanisms of action of sphingomyelin-specific pore-forming toxin,
      lysenin.
AB  - Lysenin, which is an earthworm toxin, strongly binds to sphingomyelin (SM).
      Lysenin oligomerizes on SM-rich domains and can induce cell death by forming
      pores in the membrane. In this review, the assembly of lysenin on SM-containing
      membranes is discussed mostly on the basis of the information gained by atomic
      force microscopy (AFM). AFM data show that lysenin assembles into a hexagonal
      close packed (hcp) structure by rapid reorganization of its oligomers on an
      SM/cholesterol membrane. In case of a phase-separated membrane of SM, lysenin
      induces phase mixing as a result of pore formation in SM-rich domains, and
      consequently its hcp assembly covers the entire membrane. Besides the lytic
      action, lysenin is important as an SM marker and its pore has the potential to be
      used as a biosensor in the future. These points are also highlighted in this
      review.

PMID- 28751254
TI  - Robotic Gait Training for Individuals With Cerebral Palsy: A Systematic Review
      and Meta-Analysis.
AB  - OBJECTIVE: To identify the effects of robotic gait training practices in
      individuals with cerebral palsy. DATA SOURCES: The search was performed in the
      following electronic databases: PubMed, Embase, Medline (OvidSP), Cochrane
      Database of Systematic Reviews, Web of Science, Scopus, Compendex, IEEE Xplore,
      ScienceDirect, Academic Search Premier, and Physiotherapy Evidence Database.
      STUDY SELECTION: Studies were included if they fulfilled the following criteria:
      (1) they investigated the effects of robotic gait training, (2) they involved
      patients with cerebral palsy, and (3) they enrolled patients classified between
      levels I and IV using the Gross Motor Function Classification System. DATA
      EXTRACTION: The information was extracted from the selected articles using the
      descriptive-analytical method. The Critical Review Form for Quantitative Studies
      was used to quantitate the presence of critical components in the articles. To
      perform the meta-analysis, the effects of the intervention were quantified by
      effect size (Cohen d). DATA SYNTHESIS: Of the 133 identified studies, 10 met the
      inclusion criteria. The meta-analysis showed positive effects on gait speed (.21
      [-.09, .51]), endurance (.21 [-.06, .49]), and gross motor function in dimension
      D (.18 [-.10, .45]) and dimension E (0.12 [-.15, .40]). CONCLUSIONS: The results
      obtained suggest that this training benefits people with cerebral palsy,
      specifically by increasing walking speed and endurance and improving gross motor
      function. For future studies, we suggest investigating device configuration
      parameters and conducting a large number of randomized controlled trials with
      larger sample sizes and individuals with homogeneous impairment.

PMID- 28751255
TI  - Modification of Spastic Stretch Reflexes at the Elbow by Flexion Synergy
      Expression in Individuals With Chronic Hemiparetic Stroke.
AB  - OBJECTIVE: To systematically characterize the effect of flexion synergy
      expression on the manifestation of elbow flexor stretch reflexes poststroke, and
      to relate these findings to elbow flexor stretch reflexes in individuals without
      neurologic injury. DESIGN: Controlled cohort study. SETTING: Academic medical
      center. PARTICIPANTS: Participants (N=20) included individuals with chronic
      hemiparetic stroke (n=10) and a convenience sample of individuals without
      neurologic or musculoskeletal injury (n=10). INTERVENTIONS: Participants with
      stroke were interfaced with a robotic device that precisely manipulated flexion
      synergy expression (by regulating shoulder abduction loading) while delivering
      controlled elbow extension perturbations over a wide range of velocities. This
      device was also used to elicit elbow flexor stretch reflexes during volitional
      elbow flexor activation, both in the cohort of individuals with stroke and in a
      control cohort. In both cases, the amplitude of volitional elbow flexor
      preactivation was matched to that generated involuntarily during flexion synergy
      expression. MAIN OUTCOME MEASURES: The amplitude of short- and long-latency
      stretch reflexes in the biceps brachii, assessed by electromyography, and
      expressed as a function of background muscle activation and stretch velocity.
      RESULTS: Increased shoulder abduction loading potentiated elbow flexor stretch
      reflexes via flexion synergy expression in the paretic arm. Compared with stretch
      reflexes in individuals without neurologic injury, paretic reflexes were larger
      at rest but were approximately equal to control muscles at matched levels of
      preactivation. CONCLUSIONS: Because flexion synergy expression modifies stretch
      reflexes in involved muscles, interventions that reduce flexion synergy
      expression may confer the added benefit of reducing spasticity during functional
      use of the arm.

PMID- 28751256
TI  - Inter- and Intraexaminer Reliability in Identifying and Classifying Myofascial
      Trigger Points in Shoulder Muscles.
AB  - OBJECTIVE: To determine inter- and intraexaminer reliability of examiners without
      clinical experience in identifying and classifying myofascial trigger points
      (MTPs) in the shoulder muscles of subjects asymptomatic and symptomatic for
      unilateral subacromial impact syndrome (SIS). DESIGN: Within-day inter- and
      intraexaminer reliability study. SETTING: Physical therapy department of a
      university. PARTICIPANTS: Fifty-two subjects participated in the study, 26
      symptomatic and 26 asymptomatic for unilateral SIS. INTERVENTIONS: Two examiners,
      without experience for assessing MTPs, independent and blind to the clinical
      conditions of the subjects, assessed bilaterally the presence of MTPs (present or
      absent) in 6 shoulder muscles and classified them (latent or active) on the
      affected side of the symptomatic group. Each examiner performed the same
      assessment twice in the same day. MAIN OUTCOME MEASURES: Reliability was
      calculated through percentage agreement, prevalence- and bias-adjusted kappa
      (PABAK) statistics, and weighted kappa. RESULTS: Intraexaminer reliability in
      identifying MTPs for the symptomatic and asymptomatic groups was moderate to
      perfect (PABAK, .46-1 and .60-1, respectively). Interexaminer reliability was
      between moderate and almost perfect in the 2 groups (PABAK, .46-.92), except for
      the muscles of the symptomatic group, which were below these values. With respect
      to MTP classification, intraexaminer reliability was moderate to high for most
      muscles, but interexaminer reliability was moderate for only 1 muscle (weighted
      kappa=.45), and between weak and reasonable for the rest (weighted kappa=.06
      .31). CONCLUSIONS: Intraexaminer reliability is acceptable in clinical practice
      to identify and classify MTPs. However, interexaminer reliability proved to be
      reliable only to identify MTPs, with the symptomatic side exhibiting lower values
      of reliability.

PMID- 28751257
TI  - Maternal inflammation induces immune activation of fetal microglia and leads to
      disrupted microglia immune responses, behavior, and learning performance in
      adulthood.
AB  - Maternal inflammation during pregnancy can have detrimental effects on embryonic
      development that persist during adulthood. However, the underlying mechanisms and
      insights in the responsible cell types are still largely unknown. Here we report
      the effect of maternal inflammation on fetal microglia, the innate immune cells
      of the central nervous system (CNS). In mice, a challenge with LPS during late
      gestation stages (days 15-16-17) induced a pro-inflammatory response in fetal
      microglia. Adult whole brain microglia of mice that were exposed to LPS during
      embryonic development displayed a persistent reduction in pro-inflammatory
      activation in response to a re-challenge with LPS. In contrast, hippocampal
      microglia of these mice displayed an increased inflammatory response to an LPS re
      challenge. In addition, a reduced expression of brain-derived neurotrophic factor
      (BDNF) was observed in hippocampal microglia of LPS-offspring. Microglia-derived
      BDNF has been shown to be important for learning and memory processes. In line
      with these observations, behavioral- and learning tasks with mice that were
      exposed to maternal inflammation revealed reduced home cage activity, reduced
      anxiety and reduced learning performance in a T-maze. These data show that
      exposure to maternal inflammation during late gestation results in long term
      changes in microglia responsiveness during adulthood, which is different in
      nature in hippocampus compared to total brain microglia.

PMID- 28751259
TI  - Investigation into the risk of ultra-low tar cigarettes and lung cancer.
AB  - We present analyses relating cigarette type to lung cancer based on a case
      control study in five European countries. The analyses involved 3561 cases and
      2301 controls with diseases not associated with smoking. Subjects completed a
      detailed questionnaire, including a lifetime smoking history. Analyses included
      never smokers, and those who smoked for at least 80% of the "critical period"
      from 2 to 20 years before diagnosis, ignoring those who ever smoked pipes or
      cigars, or chewed tobacco. The main analysis compares risk in those who, in the
      critical period, smoked ultra-low tar (ULT) cigarettes (machine yield <=3 mg
      tar/cigarette) for 8 + years, with those who only smoked full flavour (FF)
      cigarettes (>=10 mg tar/cigarette). After adjustment for sex, age, country,
      education, age of starting smoking, mean cigarette consumption and mean tar level
      21-50 years before interview, the odds ratio (OR) was 0.73 (95% confidence
      interval (CI) 0.50-1.06). Other analyses showed a modest, not statistically
      significant, reduction in risk with tar reduction. Risk in ULT smokers for 8 +
      years was substantially higher than in never smokers (OR 16.27, 95% CI 10.14
      26.09). The study was prematurely terminated due to cost overrun, limiting the
      power to detect an association. More evidence is needed, particularly on lifetime
      ULT smoking.

PMID- 28751260
TI  - Identification of appropriate QTc formula in beagle dogs for nonclinical safety
      assessment.
AB  - A number of drugs belonging to different therapeutic classes cause increase in QT
      interval duration, and this change has been associated with ventricular
      arrhythmias. Investigation of changes in QT intervals in toxicity studies in dogs
      is therefore of potential value. Estimation of a direct effect of drugs on the
      duration of the QT interval can be confused by drug-induced increases in heart
      rate. The objective of this evaluation was to identify an appropriate correction
      formula by comparing different formulae that could appropriately correct changes
      in QT interval in conscious beagle dogs in toxicology studies. Most commonly used
      QTc (QT correction) formulae are derived from human observations, like Bazett's
      formula and thus are not applicable for other species like dogs, where the normal
      values of heart rate is higher compared to humans. Using our historical data, we
      have established and compared different correction formulas and found that Van de
      Water's formula is the most appropriate for dog under conditions stated. However,
      there is no universally accepted formula for QTc calculation in dogs, and hence
      each organization should have its own formula, based on the analysis of data
      obtained from the strain used in its own experimental conditions.

PMID- 28751258
TI  - Distinct alpha-Synuclein strains and implications for heterogeneity among alpha
      Synucleinopathies.
AB  - The deposition of misfolded beta-sheet enriched amyloid protein is a shared
      feature of many neurodegenerative diseases. Recent studies demonstrated the
      existence of conformationally diverse strains as a common property for multiple
      amyloidogenic proteins including alpha-Synuclein (alpha-Syn). alpha-Syn is
      misfolded and aggregated in a group of neurodegenerative diseases collectively
      known as alpha-Synucleinopathies, which include Parkinson's disease (PD),
      dementia with Lewy body, multiple system atrophy and also a subset of Alzheimer's
      disease patients with concomitant PD-like Lewy bodies and neurites. While sharing
      the same pathological protein, different alpha-Synucleinopathies demonstrate
      distinct clinical and pathological phenotypes, which could result from the
      existence of diverse pathological alpha-Syn strains in patients. In this review,
      we summarized the characteristics of different alpha-Synucleinopathies and alpha
      Syn strains generated with recombinant alpha-Syn monomers. We also make
      predictions of alpha-Syn strains that could potentially exist in patients based
      on the knowledge from other amyloid proteins and the clinical and pathological
      features of different alpha-Synucleinopathies.

PMID- 28751261
TI  - Getting a molecule into the clinic: Nonclinical testing and starting dose
      considerations.
AB  - Examination of content of 35 Investigator Brochures (IBs) for small molecules
      (including some for oncology) used to support First-In-Human studies over a 2
      year period (2014-2016) showed that a mean of 37 nonclinical studies were
      performed per molecule with pharmacology, ADME and toxicology testing
      contributing 43%, 32% and 24% of the studies, respectively. Examination of 11 IBs
      for biopharmaceuticals (monoclonal antibodies) over the same time frame showed
      that the mean number of nonclinical studies was 17 studies per molecule with
      pharmacology, ADME and toxicology testing contributing 82%, 6% and 12% of the
      studies, respectively. For both types of molecule, similar numbers of
      pharmacology studies were performed but the approximately 50% fewer studies for
      biopharmaceuticals was due to considerably limited ADME and toxicology testing.
      Despite available regulatory guidance to allow calculation of a safe clinical
      starting dose, examination of how this occurred in the examined IBs showed that a
      variety of approaches are in practice, although reference to the NOAEL in
      toxicology testing is still key, whether in calculation of a Maximum Recommended
      Starting Dose (small molecules), or after use of pharmacology and/or PK data
      (especially for biopharmaceuticals) to show acceptable safety margins over doses
      used/exposure seen in toxicology studies.

PMID- 28751262
TI  - Do individuals with asthma experience airway hyper-responsiveness after exposure
      to nitrogen dioxide?
AB  - The current 100 ppb short-term National Ambient Air Quality Standard for NO2, and
      EPA's determination of a causal association for respiratory effects, are based in
      part on controlled human exposure studies evaluating airway hyper-responsiveness
      (AHR). A meta-analysis by Goodman et al. (2009) found increased AHR at 100 ppb
      NO2 but no clear concentration-response relationship up to 600 ppb, and an
      overall lack of an AHR effect for studies involving exercise or exposure to
      allergens. Several factors have been suggested to explain why effects on AHR are
      observed while people are at rest, but not during exercise or after exposure to
      allergens. These include an exercise-induced refractory period; partial reversal
      of bronchospasm from use of forced expiration maneuvers; and greater airway
      responsiveness of participants exposed to NO2 at rest. We reviewed the scientific
      evidence to determine whether there is biological support for these factors and
      found that none sufficiently explained the lack of an effect during exercise or
      after exposure to allergens. In the absence of either a consistent concentration
      response or a plausible explanation for the paradoxical AHR findings, the
      biological significance of these findings is uncertain and provides equivocal
      support for NO2 as a causal factor of AHR at these exposure levels.

PMID- 28751263
TI  - Improving insect control protein activity for GM crops: A case study
      demonstrating that increased target insect potency can be achieved without
      impacting mammalian safety.
AB  - Many insect-protected crops express insecticidal crystal (Cry) proteins derived
      from the soil bacterium Bacillus thuringiensis (Bt), including both naturally
      occurring Cry proteins and chimeric Cry proteins created through biotechnology.
      The Cry51Aa2 protein is a naturally-occurring Cry protein that was modified to
      increase its potency and expand its insect activity spectrum through amino acid
      sequence changes. The improved Cry51Aa2 variant, Cry51Aa2.834_16, and other
      developmental variants belong to the ETX_MTX2 family of proteins but share a low
      level of sequence similarity to other members of this family. This similarity is
      largely localized to the pore-forming and oligomerization protein domains, while
      sequence divergence is observed within the head domain that confers receptor
      binding specificity. The intact Cry51Aa2.834_16 protein was heat labile at
      temperatures >=55  degrees C, and was rapidly degraded after exposure to the
      gastrointestinal protease pepsin. No acute oral toxicity was observed in mice for
      three protein variants of Cry51Aa2, including Cry51Aa2.834_16, at doses exceeding
      1000 mg/kg body weight. The weight-of-evidence therefore supports the conclusion
      of safety for Cry51Aa2.834_16 and demonstrates that amino acid sequence
      modifications can be used to substantially increase insecticidal activity of a
      protein without an increased hazard to mammals.

PMID- 28751264
TI  - Allergenic potential of novel proteins - What can we learn from animal
      production?
AB  - Currently, risk assessment of the allergenic potential of novel proteins relies
      heavily on evaluating protein digestibility under normal conditions based on the
      theory that allergens are more resistant to gastrointestinal digestion than non
      allergens. There is also proposed guidance for expanded in vitro digestibility
      assay conditions to include vulnerable sub-populations. One of the underlying
      rationales for the expanded guidance is that current in vitro assays do not
      accurately replicate the range of physiological conditions. Animal scientists
      have long sought to predict protein and amino acid digestibility for precision
      nutrition. Monogastric production animals, especially swine, have
      gastrointestinal systems similar to humans, and evaluating potential allergen
      digestibility in this context may be beneficial. Currently, there is no
      compelling evidence that the mechanisms sometimes postulated to be associated
      with allergenic sensitization, e.g. antacid modification of stomach pH, are valid
      among production animals. Furthermore, examples are provided where non
      biologically representative assays are better at predicting protein and amino
      acid digestibility compared with those designed to mimic in vivo conditions.
      Greater emphasis should be made to align in vitro assessments with in vivo data.

PMID- 28751265
TI  - Risk assessment and Biomonitoring Equivalent for 2-ethylhexyl-2,3,4,5
      tetrabromobenzoate (TBB) and tetrabromobenzoic acid (TBBA).
AB  - 2-ethylhexyl-2,3,4,5 tetrabromobenzoate (TBB) is used as a flame retardant.
      Biomonitoring for TBB exposures include the metabolite, tetrabromobenzoic acid
      (TBBA), in urine. We derived a Reference Dose (RfD) for TBB and a Biomonitoring
      Equivalent (BE) for TBBA in urine. Three longer-term studies of oral gavage
      dosing of a commercial mixture BZ-54 (which includes 70% TBB) in rats were
      evaluated for deriving the RfD. The 95% lower confidence limits on the BMD
      associated with a 1 SD change from the mean (BDMLSD) values ranged from 77 to 134
      mg/kg-day. The mean BMDLSD value of 91 mg/kg-day for maternal body weight changes
      was selected as the appropriate point of departure (POD), corresponding to a
      human equivalent dose (PODHEC) of 25 mg/kg-day. A total composite uncertainty
      factor (UF) of 300 yields an RfD of 0.08 mg/kg-day. A urinary mass excretion
      fraction (Fue) of 0.6 for TBBA following oral doses of TBB in rats was used to
      calculate BEs for TBBA in urine of 2.5 mg/L and 2.5 mg/g cr. Mean (5.3 * 10-6
      mg/L) and maximum (340 * 10-6 mg/L) levels of TBBA measured in urine from human
      volunteers reported in the literature indicates margins of safety (MOS) are
      approximately 450,000 and 7,000, respectively.

PMID- 28751266
TI  - Testosterone Responders to Continuous Androgen Deprivation Therapy Show
      Considerable Variations in Testosterone Levels on Followup: Implications for
      Clinical Practice.
AB  - PURPOSE: We determined whether men on continuous androgen deprivation therapy who
      achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone
      elevations during followup and whether such events predict worse oncologic
      outcomes. MATERIALS AND METHODS: We evaluated a random, retrospective sample of
      514 patients with prostate cancer treated with continuous androgen deprivation
      therapy in whom serum testosterone was less than 0.7 nmol/l at University Health
      Network between 2007 and 2016. Patients were followed from the date of the first
      testosterone measurement of less than 0.7 nmol/l to progression to castrate
      resistance, death or study period end. Study outcomes were the development of
      testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7
      nmol/l, and progression to a castrate resistant state. Survival curves were
      constructed to determine the rate of testosterone elevations. Multivariate Cox
      regression analysis was done to assess whether elevations predicted progression
      to castrate resistance. RESULTS: Median patient age was 74 years and median
      followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients
      had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater
      than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than
      0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline
      characteristic was associated with elevations and elevations were not a
      significant predictor of progression to a castrate resistant state. CONCLUSIONS:
      Men on continuous androgen deprivation therapy in whom initial testosterone is
      less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone.
      Such a development should not trigger an immediate response from physicians as
      these events are prognostically insignificant with regard to oncologic outcomes.
      Levels are eventually reestablished at less than 0.7 nmol/l.

PMID- 28751267
TI  - Is Detrusor Contraction during Rapid Bladder Filling Caused by Cold or Warm
      Water? A Randomized, Controlled, Double-Blind Trial.
AB  - PURPOSE: We investigated whether detrusor contraction during rapid bladder
      filling is provoked by cold or warm water. MATERIALS AND METHODS: Patients with
      neurogenic lower urinary tract dysfunction were included in this randomized,
      controlled, double-blind trial. At the end of a standard urodynamic investigation
      patients underwent 2 bladder fillings using a 4C ice water test or a 36C warm
      water test saline solution at a filling speed of 100 ml per minute. The order was
      randomly selected, and patients and investigators were blinded to the order. The
      primary outcome measure was detrusor overactivity, maximum detrusor pressure and
      maximum bladder filling volume during the ice and warm water tests. RESULTS: Nine
      women and 31 men were the subject of data analysis. Neurogenic lower urinary
      tract dysfunction was caused by spinal cord injury in 33 patients and by another
      neurological disorder in 7. Irrespective of test order detrusor overactivity
      occurred significantly more often during the ice water test than during the warm
      water test (30 of 40 patients or 75% vs 25 of 40 or 63%, p = 0.02). When
      comparing the ice water test to the warm water test, maximum detrusor pressure
      was significantly higher and maximum bladder filling volume was significantly
      lower during the ice water test (each p <0.001). The order of performing the
      tests (ice water first vs warm water first) had no effect on the parameters.
      CONCLUSIONS: Our findings imply that the more frequent detrusor overactivity,
      higher maximum detrusor pressure and lower bladder filling volume during the ice
      water test compared to the warm water test were caused by cold water. This
      underlies the theory of a C-fiber mediated bladder cooling reflex in humans.

PMID- 28751268
TI  - The stem cell factor (SCF)/c-KIT system in carcinogenesis of reproductive
      tissues: What does the hormonal regulation tell us?
AB  - The tyrosine kinase receptor c-KIT and its ligand, the stem cell factor (SCF) are
      expressed in several tissues of male and female reproductive tract, playing an
      important role in the regulation of basic biological processes. The activation of
      c-KIT by SCF controls, cell survival and death, cell differentiation and
      migration. Also, the SCF/c-KIT system has been implicated in carcinogenesis of
      reproductive tissues due to its altered expression pattern or overactivation in
      consequence of gain-of-functions mutations. Over the years, it has also been
      shown that hormones, the primary regulators of reproductive function and
      causative agents in the case of hormone-dependent cancers, are also able to
      control the SCF/c-KIT tissue levels. Therefore, it is liable to suppose that
      disturbed SCF/c-KIT expression driven by (de)regulated hormone actions can be a
      relevant step towards carcinogenesis. The present review describes the SCF and c
      KIT expression in cancers of reproductive tissues, discussing the implications of
      the hormonal regulation of the SCF/c-KIT system in cancer development.
      Understanding the relationship between hormonal imbalance and the SCF/c-KIT
      expression and activity would be relevant in the context of novel therapeutic
      approaches in reproductive cancers.

PMID- 28751269
TI  - Impaired mitochondrial fusion, autophagy, biogenesis and dysregulated lipid
      metabolism is associated with preeclampsia.
AB  - Preeclampsia(PE) is a pregnancy complication that is diagnosed by the new onset
      of hypertension and proteinuria. The etiology of PE remains unclear; however,
      growing evidence indicates that mitochondrial impairment contributes to the
      pathogenesis. Therefore, we aim to investigate the function of mitochondria in
      the development of PE. The mitochondrial metabolome in preeclamptic (n = 11) and
      normal (n = 11) placentas were analyzed using Gas chromatography-mass
      spectrometry (GC-MS). Student's t-tests and receiver operating characteristic
      (ROC) curves were conducted to determine which mitochondrial metabolites differed
      significantly between the two groups. The Pathway Activity Profiling (PAPi) R
      package was used to predict which metabolic pathways were affected by PE. Western
      blot analysis was performed to identify the candidate proteins which were
      associated with mitochondrial repair regulation. GC-MS analysis demonstrated that
      higher levels of 38 metabolites and lower levels of 2 metabolites were observed
      in the placenta of patients with severe PE (sPE). Five fatty acids had an area
      under the ROC curve above 90%. Furthermore, we revealed abnormal regulation of
      mitochondrial dynamics, autophagy, and biogenesis in sPE. Our discoveries
      indicate that the compromised lipid metabolism in sPE may result from
      dysfunctional mitochondria, thus revealing new insights into the etiology of the
      disease.

PMID- 28751270
TI  - Protective antibodies against HSP60 for autoimmune inflammatory diseases.

PMID- 28751271
TI  - Early child adversity and psychopathology in adulthood: HPA axis and cognitive
      dysregulations as potential mechanisms.
AB  - Early adversity (EA) has been shown to be a potent risk factor for developing a
      psychopathology in adulthood. Alterations of the stress system in addition to
      changes in brain development have been suggested to explain some of the
      psychopathologies associated with EA. The stress response involves the activation
      of the hypothalamic-pituitary-adrenal (HPA)-axis, which leads to the production
      of glucocorticoids (GCs; cortisol in humans). Being soluble in lipids, GCs easily
      cross the blood brain barrier and access GC receptors in the hippocampus,
      prefrontal cortex and amygdala. These three brain structures do not develop at
      the same rhythm in humans and recent models suggest that exposition to EA at
      different times throughout cerebral development can induce a differential
      vulnerability to diverse mental illnesses. Although these models are of interest,
      they do not provide any mechanism(s) through which exposition to EA could lead to
      an increased vulnerability to certain mental illnesses and not others.
      Interestingly, the main brain structures that are affected by the chronic
      secretion of stress hormones during childhood (hippocampus, prefrontal cortex and
      amygdala) are differentially involved in various cognitive functions (memory,
      emotion regulation, encoding of emotional memories, etc.). It is therefore
      proposed that exposure to EA, by affecting the development of specific brain
      structures, might alter the underlying cognitive process of these brain regions,
      and increase vulnerability to specific mental disorders in adulthood.

PMID- 28751272
TI  - Effect of feeding frequency on growth, body composition, antioxidant status and
      mRNA expression of immunodependent genes before or after ammonia-N stress in
      juvenile oriental river prawn, Macrobrachium nipponense.
AB  - Feeding frequency is important for the improvement of growth performance and
      immunity of aquatic animals. In this study, the effect of feeding frequency on
      growth, body composition, antioxidant status and mRNA expression of
      immunodependent genes before or after ammonia-N stress was examined in
      Macrobrachium nipponense. Prawns were randomly assigned to one of five feeding
      frequencies (1, 2, 3, 4 and 6 times/day) following the same ration size over an 8
      week growth trial. After the feeding trial, prawns were challenged by ammonia-N.
      The weight gain of prawns fed with 3-6 times/day was significantly higher than
      that of prawns fed with 1 time/day. The best feed conversion ratio was obtained
      from prawns fed with 3-6 times/day. Body crude lipid with feeding frequency of 3,
      4 or 6 times/day was quite lower than that with 1 time/day. High feeding
      frequency (6 times/day) induced significantly elevated hepatopancreas super oxide
      dismutase and catalase activities. The malondialdehyde level in prawns fed with 6
      times/day was also significantly increased, which was higher than that of prawns
      fed with other feeding frequency. mRNA expression of toll like receptor 3 and
      myeloid differentiation primary response protein MyD88 was promoted by feeding
      frequency from 3 to 4 time/day but inhibited by high or low feeding frequency.
      Similar mRNA expression variation trends of the two genes were observed in prawns
      after ammonia-N stress. After ammonia-N challenge, the highest cumulative
      mortality was observed in prawns fed with 6 times/day, which was significantly
      higher than that of prawns fed with 2-4 times/day. These findings demonstrate
      that (1) too high feeding frequency induced oxidative stress and malondialdehyde
      accumulation, negatively affecting the health status of prawns and reduced its
      resistance to ammonia-N stress; (2) the optimal feeding frequency to improve
      growth and immune response of this species at juvenile stage is 3-4 times/day;
      (3) considering costs of labour, a feeding frequency of 3 times/day is
      recommended for this prawn.

PMID- 28751273
TI  - Overexpression and characterization of a recombinant l-ribose isomerase from
      Actinotalea fermentans ATCC 43279.
AB  - A putative l-ribose isomerase (EC 5.3.1.B3, l-RI) gene of Actinotalea fermentans
      ATCC 43279 was chemically synthesized, subcloned into pET-21b vector, and then
      overexpressed in Escherichia coli. After 0.5mM IPTG induction at 20 degrees C for
      20h, the recombinant l-RI was highly expressed with up to 50% of the total
      proteins. About 70% of the expressed l-RI appeared in the cell-free extract as a
      soluble form, and a high yield of active l-RI, 23,800U/L or 952U/g of wet cells,
      was achieved. The purified recombinant l-RI demonstrated its optimal activity at
      45 degrees C and pH 8 (in tricine-NaOH buffer). Metal ions are not required for l
      RI activity, but Hg2+ inhibits its activity completely. The enzyme has a half
      life of 74min at 50 degrees C and an equilibrium ratio of 30:70 between l
      ribulose and l-ribose at 45 degrees C. The Vmax, kcat, KM, and catalytic
      efficiency (kcat/KM) of the recombinant l-RI against l-ribose are 232U/mg,
      6700min-1, 31.3mM, and 214min-1mM-1, respectively. The high expression yield of
      the active recombinant A. fermentansl-RI and its highest Vmax, kcat, and
      catalytic efficiency among the characterized recombinant l-RIs suggest that this
      recombinant enzyme shows a potential application to produce l-ribose in industry.

PMID- 28751274
TI  - A step forward in laccase exploitation: Recombinant production and evaluation of
      techno-economic feasibility of the process.
AB  - Protein heterologous production offers viable opportunities to tailor laccase
      properties to specific industrial needs. The high redox potential laccase POXA1b
      from Pleurotus ostreatus was chosen as case study of marketable enzyme, due to
      its desirable properties in terms of activity/stability profile, and already
      assessed applicability. POXA1b was heterologously produced in Pichia pastoris by
      investigating the effect of inducible and constitutive expression systems on both
      the yield and the cost of its production. System performances were first assessed
      in shaken-flasks and then scaled-up in bioreactor. The production level obtained
      in the inducible system is 42U/mL, while the activity value achieved with the
      constitutive one is 60U/mL, the highest obtained in constitutive systems so far.
      The economic feasibility of recombinant laccase production was simulated,
      describing the case of an Italian small-medium enterprise. Two scenarios were
      evaluated: Scenario (I) production based on methanol inducible system; Scenario
      (II) production based on the constitutive system, fed with glycerol. At all the
      scales the glycerol-based fermentation is more economic than the methanol-based
      one. The price forecast for rPOXA1b production is 0.34?kU-1 for glycerol-based
      process, and is very competitive with the current price of commercial laccase.

PMID- 28751275
TI  - Lipase-catalyzed synthesis of sucrose monoester: Increased productivity by
      combining enzyme pretreatment and non-aqueous biphasic medium.
AB  - Sucrose monocaprate was synthesized by carrying out a lipase-catalyzed
      transesterification in a non-aqueous biphasic medium. Vinyl caprate was
      mechanically dispersed into a solution of sucrose in DMSO. The use of DMSO
      allowed increasing sucrose concentration up to 0.7M (in DMSO). The denaturing
      effect of DMSO on lipase was avoided by pretreatment of lipase by pH adjustment
      in the presence of crown ether. This pretreatment maintained a significant
      catalytic activity which led to 0.2M sucrose monoester within 1h at 50 degrees C,
      which represented higher productivity than already reported. Detailed structural
      characterization revealed that only monoester was recovered and the 2-O-acylated
      sucrose monocaprate was the major isomer in the final product.

PMID- 28751276
TI  - Chemoenzymatic synthesis of statine side chain building blocks and application in
      the total synthesis of the cholesterol-lowering compound solistatin.
AB  - The synthesis and enzymatic reduction of several 6-substituted dioxohexanoates
      are presented. Two-step syntheses of tert-butyl 6-bromo-3,5-dioxohexanoate and
      the corresponding 6-hydroxy compound have been achieved in 89% and 59% yield,
      respectively. Regio- and enantioselective reduction of these diketones and of the
      6-chloro derivative with alcohol dehydrogenase from Lactobacillus brevis (LBADH)
      gave the (5S)-5-hydroxy-3-oxo products with enantiomeric excesses of 91%, 98.4%,
      and >99.5%, respectively. Chain elongation of the reduction products by one
      carbon via cyanide addition, and by more than one carbon by Julia-Kocienski
      olefination, gave access to well-established statine side-chain building blocks.
      Application in the synthesis of the cholesterol-lowering natural compound
      solistatin is given.

PMID- 28751277
TI  - Computational study of the binding mechanism of medium chain acyl-CoA synthetase
      with substrate in Methanosarcina acetivorans.
AB  - The acyl-AMP forming family of adenylating enzymes catalyzes the formation of
      acyl-CoA from an acyl substrate, ATP, and CoA, which is a metabolite of many
      catabolic and anabolic processes. The medium-chain acyl-CoA synthetase from
      Methanosarcina acetivorans, designated MacsMa, uses 2-methylbutyrate as its
      preferred substrate. It is reported that the interaction between the sidechain of
      Cys298 and Lys256 of this enzyme is important for the catalytic activity. The
      mutation of these residues resulted in the changes of the structure stability and
      the reduced or absence catalytic activity. In the present study, the binding
      mechanism between the substrate 2-methylbutyrate- AMP (2MeBA) and MacsMa were
      explored by integrating multiple computational methods including molecular
      docking, molecular dynamics simulations, binding free energy calculation, active
      site access channel analysis and principal component analysis. The binding free
      energy between WT, mutated Macs and substrate was calculated by MM-GBSA method,
      which indicated that the binding affinity between this enzyme and substrate was
      stronger in the WT than that in the mutated forms (K256L, K256T and C298Y). Per
      residue binding free energy decomposition identified some residues, such as
      Gly327, Phe350, Gly351, Gln352 and Lys461, which are important for the enzyme and
      substrate binding affinity. The access channels of the mutant system (MacsK256L,
      MacsK256T and MacsC298Y) were found to be different from those in the wild-type
      systems. It suggested that K256L and C298Y induced larger flexibility to the
      overall protein compared with the WT, whereas K256T induced larger flexibility to
      the partial protein compared with the WT by PCA vector porcupines. This study
      provides novel insight to understand the substrate binding mechanism of Macs and
      useful information for the rational enzyme design.

PMID- 28751278
TI  - Production of 3-hydroxypropionic acid by balancing the pathway enzymes using
      synthetic cassette architecture.
AB  - Biological 3-hydroxypropionic acid (3-HP) production from glycerol is a two-step
      reaction catalyzed by glycerol dehydratase (GDHt) and aldehyde dehydrogenase
      (ALDH). Recombinant strains developed for 3-HP production often suffer from the
      accumulation of a toxic intermediate, 3-hydroxypropionaldehyde (3-HPA). In order
      to avoid 3-HPA accumulation, balancing of the two enzymatic activities, in the
      present study, was attempted by employment of synthetic-regulatory cassettes
      comprising varying-strength promoters and bicistronic ribosome-binding sites
      (RBSs). When tested in recombinant Escherichia coli, the cassettes could
      precisely and differentially control the gene expression in transcription,
      protein expression and enzymatic activity. Five recombinant strains showing
      different expressions for GDHt were developed and studied for 3-HPA accumulation
      and 3-HP production. It was found that 3-HPA accumulation could be completely
      abolished when expressing ALDH at a level approximately 8-fold higher than that
      of GDHt. One of the strains, SP4, produced 625mM (56.4g/L) of 3-HP in a fed-batch
      bioreactor, though late-period production was limited by acetate accumulation.
      Overall, this study demonstrated the importance of pathway balancing in 3-HP
      production as well as the utility of the synthetic cassette architecture for
      precise control of bacterial gene expression.

PMID- 28751280
TI  - Reform of the outside nomenclature biomedical tests in France: a two year review.

PMID- 28751279
TI  - The extracellular role of DNA damage repair protein APE1 in regulation of IL-6
      expression.
AB  - The human apurinic/apyrimidinic endonuclease 1 (APE1) is a pleiotropic nuclear
      protein with roles in DNA base excision repair pathway as well as in regulation
      of transcription. Recently, the presence of extracellular plasma APE1 was
      reported in endotoxemic rats. However, the biological significance and the
      extracellular function of APE1 remain unclear. In this study, we found that
      monocytes secrete APE1 upon inflammatory challenges. Challenging the monocytic
      cells with extracellular APE1 resulted in the increased expression and secretion
      of the pro-inflammatory cytokine IL-6. Additionally, the extracellular APE1
      treatment activated the transcription factor NF-kappaB, followed by its increased
      occupancy at the IL-6 promoter, resulting in the induction of IL-6 expression.
      APE1-induced IL-6 further served to elicit autocrine and paracrine cellular
      responses. Moreover, the extracellular IL-6 promoted the secretion of APE1, thus
      indicating a functional feedforward loop in this pathway. Furthermore, we show
      that APE1 is secreted through extracellular vesicles formation via endosomal
      sorting complex required for transport (ESCRT)-dependent pathway. Together, our
      study demonstrates a novel role of extracellular APE1 in IL-6-dependent cellular
      responses.

PMID- 28751281
TI  - Biotin: an emerging analytical interference.

PMID- 28751282
TI  - Stability of blood potassium: effects of duration, temperature and transport
      during 10 hours storage of human whole blood in serum and plasma.
AB  - To comply with the pre-analytical requirements of ISO EN 15189, we investigated
      the stability of potassium, a very critical and sensitive analyte. We took into
      count effects of duration, temperature and transport after 10 hours storage of
      human whole blood in serum and plasma. Blood of 12 healthy subjects was analyzed
      after 4, 6, 8 and 10 hours of storage. Three study groups were designed: samples
      stored in laboratory at room temperature, transported by car during 4 hours at a
      temperature of 21+/-1C, with or without previous thermal shock (20 min at 4+/-1
      C) before transportation. Variations in concentration were expressed as mean bias
      from baseline using the analytical change limit (ACL) and the reference change
      value (RCV). Using RCV, we considered that potassium was biologically stable
      during 10 hours whatever our study groups. Considering ACL, potassium in serum
      was not stable after the thermal shock. We conclude that whole blood in lithium
      heparin tubes may be used for routine potassium analysis even if long car
      transportation and previous thermal shock is involved. It confirms that potassium
      analysis can be still performed in locations distant from a medical laboratory.

PMID- 28751283
TI  - Clinical pathologists and physician in France: which partnership and which
      future?
AB  - Medical biology is a major area of medical specialization in French health care
      system. It is going through massive changes in public as in private sector since
      the 2010 Ballereau edict with the merging of laboratories and new quality
      standards based on accreditation. We have suggested that physicians had a
      negative feeling about the restructuring of medical biology in recent years. An
      electronic questionnaire has been sent to physicians so as to find out what they
      thought about the evolution of medical biology and to get suggestions to improve
      the taking care of the patient. Have answered 1364 residents and physicians from
      all specializations, all regions, practicing in public or private hospitals or in
      general practices. Doctors have on the whole a negative feeling about how medical
      biology has evolved in recent years thinking that it is moving towards
      industrialization with delay increasing. They are convinced that tests must be
      made on site. They remain satisfied with the quality of the tests and have a
      positive feeling about scientific evolutions and are in favor of a better
      clinical-biological cooperation. The study points out a lack of clarity
      concerning how private laboratories are organized and how they operate. A
      computer link between clinical pathologists and physicians to access results and
      a list of urgent medical examinations could be set up so as to have a more rapid
      access to results. Rapid diagnostic tests or delocalized biology could be used
      but doctors do not want these tests to replace the clinical pathologist.

PMID- 28751284
TI  - Search for biomarkers of neurosarcoidosis by proteomic analysis of cerebrospinal
      fluid.
AB  - Sarcoidosis is a systemic granulomatous disease, which mostly affects lung.
      Central nervous system can be affected causing a neurosarcoidosis in 5 to 15% of
      all sarcoidosis patients. The definitive diagnosis is established on histological
      examination of brain granulomas. Angiotensin converting enzyme is currently the
      most relevant biomarker to confirm a probable diagnosis; however, it lacks
      sensitivity and specificity. We aim to find novel biomarkers of neurosarcoidosis
      in cerebrospinal fluid (CSF) by proteomic analysis, combining two-dimension
      electrophoresis (2-DE) and mass spectrometry. We performed CSF proteomic profile
      of both patients (group S) and control subjects (group H). The statistical
      analysis of 2-D gels highlighted 42 spots significantly different between the two
      groups. Twenty-five spots were subjected to tryptic digestion; the peptides were
      analyzed by MALDI-TOF and MALDI-TOF-TOF, giving rise to 10 identifications. Among
      the identified proteins, low-molecular-mass-kininogen and vitamin-D-binding
      protein were increased, while transthyretin was decreased. These proteins have
      probably an intrathecal source and could be interesting candidates. This study
      led to the identification of several proteins which can be used for the diagnosis
      and/or monitoring of neurosarcoidosis. These putative biomarkers have to be
      confirmed on a larger cohort and assessed for their sensitivity and specificity.

PMID- 28751285
TI  - Comparison of human embryomorphokinetic parameters in sequential or global
      culture media.
AB  - A prospective study on randomized patients was conducted to determine how
      morphokinetic parameters are altered in embryos grown in sequential versus global
      culture media. Eleven morphokinetic parameters of 160 single embryos transferred
      were analyzed by time lapse imaging involving two University-affiliated in vitro
      fertilization (IVF) centers. We found that the fading of the two pronuclei
      occurred earlier in global (22.56+/-2.15 hpi) versus sequential media (23.63+/
      2.71 hpi; p=0.0297). Likewise, the first cleavage started earlier at 24.52+/-2.33
      hpi vs 25.76+/-2.95 hpi (p=0.0158). Also, the first cytokinesis was shorter in
      global medium, lasting 18+/-10.2 minutes in global versus 36+/-37.8 minutes in
      sequential culture medium (p <0.0001). We also observed a significant shortening
      in the duration of the 2-cell stage in sequential medium: 10.64 h+/-2.75 versus
      11.66 h+/-1.11 in global medium (p=0.0225) which suggested a faster progression
      of the embryos through their first mitotic cell cycle. In conclusion,
      morphokinetic analysis of human embryos by Time lapse imaging reveals significant
      differences in five kinetic variables according to culture medium. Our study
      highlights the need to adapt morphokinetic analysis accordingly to the type of
      media used to best support human early embryo development.

PMID- 28751286
TI  - Troponin elevation in other conditions than acute coronary syndromes.
AB  - Troponin is a specific cardiac infarction isoform (TnIc, TnTc) and its
      determination is used for the diagnosis of myocardial infarction even with normal
      Electrocardiography. The increase of cardiac troponins occurs in a variety of
      clinical situations without an acute coronary syndrome (ACS), cardiologists and
      emergency physicians are often confronted with positive troponins that are
      difficult to interpret. Few data exist about the occurrence, the clinical
      characteristics and the predictive value in case of absence of ACS. The objective
      of this study is to present the main extracardiac causes responsible of the
      increase of TnIc. We present some clinical cases that illustrate this diagnostic
      problem. A troponin elevation is observed in myopericarditis, renal failure,
      heart failure, pulmonary embolism, septic shock, rhabdomyolysis, stroke and
      others where there is a myocardial damage unrelated to coronary occlusion. Many
      cases of false positives, which raise the possibility of analytical
      interferences, must be identified.

PMID- 28751287
TI  - Clinical value of CA 15-3 for detection of distant metastases in newly diagnosed
      breast cancer.
AB  - The aim of the study is to investigate the clinical value of CA 15-3 for
      detection of distant metastases (DM) in newly diagnosed breast cancer. This
      retrospective study focuses on a population of 1,007 patients with locally
      advanced breast cancer (n=561) or metastatic breast cancer (n=446) diagnosed at
      the CGFL (Centre Georges Francois Leclerc) from March 1998 to October 2013. These
      patients underwent a measurement of CA 15-3 and an assessment of extension before
      any treatment. The cut-off value of CA 15-3 was determined and verified on two
      independents subpopulations determined in drawing lots. The ROC curve shows an
      AUC of 0.85 (p<0.0001). At the threshold of 50 kU/L, CA 15-3 before treatment has
      a predictive value on the existence of DM independently of the other prognostics
      factors. This predictive value has been found in every molecular subtype (AUC>=
      0.70; p<= 0,085). The rate of false negative is of 38% and depends on the number
      and the type of the metastatic localization. Among the 28 patients without DM and
      a CA 15-3> 50 kU/L, 13 have developed DM and 11 died of cancer. In conclusion,
      these facts confirm the independently predictive value of CA 15-3 before
      treatment on the existence of DM and the complementarity of the marker with the
      assessment of extension by imagery.

PMID- 28751288
TI  - Clinical value of CEA for detection of distant metastases in newly diagnosed
      breast cancer: comparison with CA 15-3.
AB  - The aim of the study is to investigate the clinical value of CEA
      (carcinoembryonic antigen) for detection of distant metastases (DM) in newly
      diagnosed breast cancer. This retrospective study focuses on a population of 929
      patients with locally advanced breast cancer (n=521) or metastatic breast cancer
      (n=408) diagnosed at the CGFL (Centre Georges Francois Leclerc) from 1998 to
      2014. These patients underwent a measurement of CA 15-3, a measurement of CEA and
      an assessment of extension before any treatment. The initial concentrations of
      CEA are correlated with conventional prognostic factors. The cut-off value of CEA
      was determined and verified on two independents subpopulations determined in
      drawing lots. The ROC curve shows an AUC of 0.82 (p<0.0001). At the threshold of
      6.7 MUg/L, CEA before treatment has a predictive value on the existence of DM
      independently of the CA 15-3 and other prognostic factors. The combination of CEA
      and CA 15-3 increases significantly the predictive value of CA 15-3 on the whole
      population (sensitivity increased by 9%) and on tumors expressing hormonal
      receptors. Concerning the only CEA the rate of false negative is of 52% and
      depends on the number and the type of the metastatic localization. Among the 28
      patients without DM and a CEA > 6.7 MUg/L, 15 have developed DM and 2 a new
      cancer. Thirteen will die of cancer. In conclusion, these facts confirm the
      independently predictive value of CEA before treatment on the existence of DM and
      its complementarity with CA 15-3 during the assessment of extension by imagery.

PMID- 28751289
TI  - A new case of IgE multiple myeloma with review of literature.
AB  - IgE myeloma is an extremely rare disease characterized by frequent plasma cell
      leukemia, little monoclonal-spike on electrophoresis, an high incidence of
      t(11;14) translocation and a worse survival than those with common myelomas. We
      report here a new case of IgE myeloma and discuss clinical presentation,
      biological features and therapeutic option.

PMID- 28751290
TI  - Myoadenylate deaminase deficiency: a frequent cause of muscle pain A case
      detected by exercise testing.
AB  - Myoadenylate deaminase deficit (MAD, MIM#615511) is the most common cause of
      metabolic myopathies with an estimated prevalence of 1-2% in the general
      population. We report the case of a 39-year-old man suffering from severe
      skeletal muscle pain that had developed gradually for 4 years. A moderate
      increase in creatine kinase (CK) was the only biological sign observed. This
      study takes a closer look at a common but poorly known pathology and highlights
      the interest of the dynamic metabolic investigations carried out during exercise
      stress test with a cycle ergometer. Our non-invasive clinical and biological
      examination, at the interface between physiology and biology, disclosed the total
      absence of a physiological increase in plasma ammonia evocative of MAD. However,
      MAD was later confirmed by histochemistry and molecular studies, which revealed
      the presence of the recurrent homozygous pathogenic variant affecting the
      adenosine monophosphate deaminase 1 gene (AMPD1) in most patients with MAD.

PMID- 28751291
TI  - A case of EDTA-related in vitro platelet degranulation.
AB  - A 71 year-old woman is admitted to Le Mans hospital center for management of a
      chronic skin lesion. She has no personal nor familial bleeding history and does
      not take any medication. In peripheral blood collected with EDTA (ethylene
      diamine tetra-acetate), the platelet count is elevated and the blood film shows
      uniformly grey platelets. In sodium citrate-collected blood, platelets show no
      abnormality. We describe an EDTA-related artifact that is not to be mistaken for
      grey platelet syndrome.

PMID- 28751292
TI  - Malaria following a blood exposure accident: about a case.
AB  - Each year, hundreds of cases of malaria are reported in Morocco and occur after
      anopheles in patients who have stayed in endemic areas, but transmission
      following an accident of exposure to blood is rare or exceptional, only about 20
      cases are published. We report a case of malaria in a nursing staff following an
      accidental sting with a catheter needle.

PMID- 28751293
TI  - A case report of pseudo grey platelet syndrome with citrate-induced
      pseudothrombocytopenia: those artifacts may interfere in the platelet numeration
      and lead to critical misdiagnosis.
AB  - The pseudo grey platelet syndrome is a rare artifact due to the degranulation of
      platelets caused, in vitro, by EDTA. This phenomenon is likely to disturb the
      platelet numeration and it is essential not to mistake it for a grey syndrome
      platelet, which is a constitutional thrombopathy with macrothrombopenia, in order
      to avoid specialized tests, or even misdiagnosis. Indeed, these two entities are
      cytologically alike, as grey platelets are found on the blood smear of a sample
      collected on EDTA in both cases. We here describe the case of a patient admitted
      in Colmar's Hospital for a chronic thrombocytopenia, associating both a
      pseudothrombocytopenia and a pseudo grey platelet syndrome.

PMID- 28751294
TI  - Drowsiness and uncommon fever in a child after cannabis ingestion.
AB  - Trivialization of cannabis consumption goes hand in hand with a growing exposure
      of children and the number of cannabis poisoning cases is steadily increasing. As
      clinical presentation can be different from what is currently seen in adults,
      added to the fact that it is not always suspected, diagnosis of cannabis
      intoxication in children is often delayed or missed. A 16-month-old girl was
      admitted to the pediatric emergency unit for an important drowsiness combined to
      moderate fever. After elimination of infectious causes, a toxic origin was
      considered and biological analyses led to the diagnosis of involuntary acute
      cannabis intoxication. In conclusion, cannabis intoxication in child has uncommon
      presentations compared to that seen in adults. In this context, biological
      analyses have a great importance for a rapid diagnosis and also for the
      understanding intoxication circumstance. This is of paramount importance because
      it may lead to consider child protection measures.

PMID- 28751295
TI  - Pseudo-Bartter syndrome as the sole manifestation of cystic fibrosis in a child
      with 711+G>T/IVS8-5T mutation: a new face of an old disease.
AB  - Pseudo-Bartter syndrome (PBS) describes an uncommon complication of cystic
      fibrosis leading to hypochloraemic, hypokalaemic metabolic alkalosis. PBS as the
      sole manifestation of cystic fibrosis in children is extremely rare and has never
      been described in patients carrying 5T variant. We report a clinical, biochemical
      and genetic study of a four year-old boy presenting a pseudo-Bartter syndrome as
      the sole manifestation of cystic fibrosis. All 27 exons and the flanking intron
      regions of the CFTR gene were analysed by PCR and direct sequencing. Direct
      sequencing was also used to analyse TGmTn and M470V polymorphisms in the patient
      and his parents. Two sweat tests were abnormal with elevated chloride levels at
      78 and 88 mmol/L. DNA sequencing revealed a heterozygous mutation 711+1 G>T and
      an IVS8-T5 allele. The mutation 711+1 G>T is in trans with the IVS8-T5-TG11
      allele and the child carried M470/V470 genotype. To the best of our knowledge,
      the genotype 711+1 G>T /IVS8-5T found in our patient is described for the first
      time. The role of TG11-5T-V470 allele in cases of cystic fibrosis with PB
      syndrome remains to be determined.

PMID- 28751296
TI  - Methanol detection after esmolol infusion in intensive care unit: a case report.

PMID- 28751298
TI  - The Relationship Between Individual Characteristics and Interest in Using a
      Mobile Phone App for HIV Self-Management: Observational Cohort Study of People
      Living With HIV.
AB  - BACKGROUND: The human immunodeficiency virus (HIV) continues to be a major health
      issue in the United States, and an estimated 1.2 million people in the United
      States are living with HIV. As part of Healthy People 2020, the Office of Disease
      Prevention and Health Promotion has targeted the persistent demographic and
      geographic disparities in HIV prevalence and management. Preliminary evidence
      suggests that mobile health technology (smartphone apps) may be a promising way
      to support HIV self-management among vulnerable populations of people living with
      HIV (PLWH) who lack access to appropriate health care services. OBJECTIVE: This
      study examines the association between individual characteristics of PLWH and
      level of interest in using a free mobile phone app for HIV self-management.
      METHODS: This study was conducted using cross-sectional survey data collected in
      the Florida Cohort Study between 2014 and 2016 (N=766). Associations between
      individual characteristics of PLWH and level of interest in using a free mobile
      phone app for HIV self-management were examined using bivariate analysis and
      logistic regression. RESULTS: Overall, 85.5% (655/766) of respondents were
      interested in using a free mobile phone app that supports HIV self-management.
      Participants expressed the highest interest in app functions that facilitate
      communication with health care providers (568/740, 76.8%) or help to identify
      relevant health care services (556/745 74.6%). Age (OR 0.959, 95% CI 0.936
      0.982), education (OR 1.281, 95% CI 1.027-1.598) and disability or inability to
      work (OR 0.296, 95% CI 0.145-0.606) were all significantly associated with being
      interested in using a free mobile phone app for HIV self-management. CONCLUSIONS:
      This study indicates that a majority of PLWH are interested in using a free
      mobile phone app to self-manage their condition. The findings can inform the
      development of mobile phone apps that support effective HIV self-management.

PMID- 28751299
TI  - Personalized Web-Based Advice in Combination With Well-Child Visits to Prevent
      Overweight in Young Children: Cluster Randomized Controlled Trial.
AB  - BACKGROUND: Overweight is a major health issue, and parent-targeted interventions
      to promote healthy development in children are needed. OBJECTIVE: The study aimed
      to evaluate E-health4Uth Healthy Toddler, an intervention that educates parents
      of children aged 18 to 24 months regarding health-related behaviors, as compared
      with usual care. The effect of this intervention on the following primary
      outcomes was evaluated when the children were 36 months of age: health-related
      behaviors (breakfast daily, activity and outside play, sweetened beverage
      consumption, television (TV) viewing and computer time), body mass index (BMI),
      and the prevalence of overweight and obesity. METHODS: The BeeBOFT (acronym for
      breastfeeding, breakfast daily, outside playing, few sweet drinks, less TV
      viewing) study is a cluster randomized controlled trial involving 51 Youth Health
      Care (YHC) teams. In total, 1094 parents participated in the control group, and
      1008 parents participated in the E-health4Uth Healthy Toddler intervention group.
      The intervention consisted of Web-based personalized advice given to parents who
      completed an eHealth module and discussion of the advice during a regular well
      child visit. In this study the eHealth module was offered to parents before two
      regular well-child visits at 18 and 24 months of age. During the well-child
      visits, the parents' personalized advice was combined with face-to-face
      counseling provided by the YHC professional. Parents in the control group
      received usual care, consisting of the regular well-child visits during which
      general information on child health-related behavior was provided to parents.
      Parents completed questionnaires regarding family characteristics and health
      related behaviors when the child was 1 month (inclusion), 6 months, 14 months,
      and 36 months (follow-up) of age. The child's height and weight were measured by
      trained health care professionals from birth through 36 months of age at fixed
      time points. Multilevel linear and logistic regression models were used to
      evaluate the primary outcomes at 36 months of age. RESULTS: At 36 months, we
      observed no differences between health-related behaviors of children, BMI or the
      percentage of children having overweight or obesity in the control and
      intervention group (P>.05). An analysis of the intervention effect revealed that
      boys benefited from eating breakfast daily, non-Dutch children spent more time
      being active or playing outdoors, children of low-educated parents and of
      overweight and obese mothers spent less time watching TV or using the computer,
      and children of normal weight mothers drank less sweetened beverages (P<.05)
      compared with the control group. CONCLUSIONS: The E-health4Uth Healthy Toddler
      intervention resulted in small improvements in health-related behaviors among
      subgroups but had no significant effects with respect to the children's BMI. We
      conclude that the E-health4Uth Healthy Toddler intervention may be useful for
      pediatric health care professionals in terms of providing parents with
      personalized information regarding their child's health-related behaviors. TRIAL
      REGISTRATION: Netherlands Trial Register: NTR1831;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1831 (Archived by
      WebCite at http://www.webcitation.org/6mm5YFOB0).

PMID- 28751300
TI  - Twelve-Month Follow-Up of a Randomized Controlled Trial of Internet-Based Guided
      Self-Help for Parents of Children on Cancer Treatment.
AB  - BACKGROUND: A substantial proportion of parents of children on cancer treatment
      report psychological distress such as symptoms of post-traumatic stress (PTSS),
      depression, and anxiety. During their child's treatment many parents also
      experience an economic burden. OBJECTIVE: The aim of this study was to evaluate
      the long-term efficacy of Internet-based guided self-help for parents of children
      on cancer treatment. METHODS: This study was a parallel randomized controlled
      trial comparing a 10-week Internet-based guided self-help program, including
      weekly support from a therapist via encrypted email, with a wait-list control
      condition. The intervention was based on cognitive behavior therapy (CBT) and
      focused on psychoeducation and skills to cope with difficult thoughts and
      feelings. Primary outcome was self-reported PTSS. Secondary outcomes were self
      reported symptoms of depression, anxiety, health care consumption, and sick leave
      during the past month. Outcomes were assessed pre- and postintervention and at 12
      month follow-up. Parents of children on cancer treatment were invited by health
      care personnel at pediatric oncology centers, and parents meeting the modified
      symptom criteria on the PCL-C were included in the study. Self-report assessments
      were provided on the Web. RESULTS: A total of 58 parents of children on cancer
      treatment (median months since diagnosis=3) were included in the study
      (intervention n=31 and control n=27). A total of 18 participants completed the
      intervention, and 16 participants in each group participated in the 12-month
      follow-up. Intention-to-treat analyses revealed significant effects in favor of
      the intervention on the primary outcome PTSS, with large between-group effect
      sizes at postassessment (d=0.89; 95% CI 0.35-1.43) and at 12-month follow-up
      (d=0.78; 95% CI 0.25-1.32). Significant effects in favor of the intervention on
      the secondary outcomes depression and anxiety were also observed. However, there
      was no evidence for intervention efficacy on health care consumption or sick
      leave. CONCLUSIONS: Using the Internet to provide psychological interventions
      shows promise as an effective mode of delivery for parents reporting an increased
      level of PTSS and who consider Internet-based interventions as a viable option.
      Future research should corroborate these findings and also develop and evaluate
      interventions and policies that may help ameliorate the economic burden that
      parents may face during their child's treatment for cancer.

PMID- 28751301
TI  - Consumer Adoption of Personal Health Record Systems: A Self-Determination Theory
      Perspective.
AB  - BACKGROUND: Personal Health Records (PHR) systems provide individuals with access
      and control over their health information and consequently can support
      individuals in becoming active participants, rather than passive recipients, in
      their own care process. In spite of numerous benefits suggested for consumers'
      utilizing PHR systems, research has shown that such systems are not yet widely
      adopted or well known to consumers. Bearing in mind the potential benefits of
      PHRs to consumers and their potential interest in these systems-and that similar
      to any other type of information system, adoption is a prerequisite for realizing
      the potential benefits of PHR systems-research is needed to understand how to
      enhance the adoption rates for PHR systems. OBJECTIVE: This research seeks to
      understand how individuals' intentions to adopt PHR systems are affected by their
      self-determination in managing their own health-the extent of their ability to
      take an active role in managing their own health. As such, this research aims to
      develop and empirically validate a theoretical model that explains PHR systems
      adoption by the general public through the integration of theories from the
      information systems and psychology literatures. METHODS: This research employs a
      cross-sectional survey method targeted at the Canadian general public without any
      prior experience in using PHR systems. A partial least squares approach to
      structural equation modeling was used to validate the proposed research model of
      this study (N=159). RESULTS: Individuals with higher levels of ability to manage
      their own health (self-determination) are more likely to adopt PHR systems since
      they have more positive perceptions regarding the use of such systems. Further,
      such self-determination is fueled by autonomy support from consumers' physicians
      as well as the consumers' personality trait of autonomy orientation. CONCLUSIONS:
      This study advances our theoretical understanding of PHR systems adoption. It
      also contributes to practice by providing insightful implications for designing,
      promoting, and facilitating the use of PHR systems among consumers.

PMID- 28751302
TI  - Smartphone-Based Endoscope System for Advanced Point-of-Care Diagnostics:
      Feasibility Study.
AB  - BACKGROUND: Endoscopic technique is often applied for the diagnosis of diseases
      affecting internal organs and image-guidance of surgical procedures. Although the
      endoscope has become an indispensable tool in the clinic, its utility has been
      limited to medical offices or operating rooms because of the large size of its
      ancillary devices. In addition, the basic design and imaging capability of the
      system have remained relatively unchanged for decades. OBJECTIVE: The objective
      of this study was to develop a smartphone-based endoscope system capable of
      advanced endoscopic functionalities in a compact size and at an affordable cost
      and to demonstrate its feasibility of point-of-care through human subject
      imaging. METHODS: We developed and designed to set up a smartphone-based
      endoscope system, incorporating a portable light source, relay-lens, custom
      adapter, and homebuilt Android app. We attached three different types of existing
      rigid or flexible endoscopic probes to our system and captured the endoscopic
      images using the homebuilt app. Both smartphone-based endoscope system and
      commercialized clinical endoscope system were utilized to compare the imaging
      quality and performance. Connecting the head-mounted display (HMD) wirelessly,
      the smartphone-based endoscope system could superimpose an endoscopic image to
      real-world view. RESULTS: A total of 15 volunteers who were accepted into our
      study were captured using our smartphone-based endoscope system, as well as the
      commercialized clinical endoscope system. It was found that the imaging
      performance of our device had acceptable quality compared with that of the
      conventional endoscope system in the clinical setting. In addition, images
      captured from the HMD used in the smartphone-based endoscope system improved eye
      hand coordination between the manipulating site and the smartphone screen, which
      in turn reduced spatial disorientation. CONCLUSIONS: The performance of our
      endoscope system was evaluated against a commercial system in routine
      otolaryngology examinations. We also demonstrated and evaluated the feasibility
      of conducting endoscopic procedures through a custom HMD.

PMID- 28751303
TI  - Diagnosis and early management of inflammatory arthritis.

PMID- 28751304
TI  - A lipodystrophy-causing lamin A mutant alters conformation and epigenetic
      regulation of the anti-adipogenic MIR335 locus.
AB  - Mutations in the Lamin A/C (LMNA) gene-encoding nuclear LMNA cause laminopathies,
      which include partial lipodystrophies associated with metabolic syndromes. The
      lipodystrophy-associated LMNA p.R482W mutation is known to impair adipogenic
      differentiation, but the mechanisms involved are unclear. We show in this study
      that the lamin A p.R482W hot spot mutation prevents adipogenic gene expression by
      epigenetically deregulating long-range enhancers of the anti-adipogenic MIR335
      microRNA gene in human adipocyte progenitor cells. The R482W mutation results in
      a loss of function of differentiation-dependent lamin A binding to the MIR335
      locus. This impairs H3K27 methylation and instead favors H3K27 acetylation on
      MIR335 enhancers. The lamin A mutation further promotes spatial clustering of
      MIR335 enhancer and promoter elements along with overexpression of the MIR355
      gene after adipogenic induction. Our results link a laminopathy-causing lamin A
      mutation to an unsuspected deregulation of chromatin states and spatial
      conformation of an miRNA locus critical for adipose progenitor cell fate.

PMID- 28751305
TI  - Dlx3b/4b is required for early-born but not later-forming sensory hair cells
      during zebrafish inner ear development.
AB  - Morpholino-mediated knockdown has shown that the homeodomain transcription
      factors Dlx3b and Dlx4b are essential for proper induction of the otic
      epibranchial progenitor domain (OEPD), as well as subsequent formation of sensory
      hair cells in the developing zebrafish inner ear. However, increasing use of
      reverse genetic approaches has revealed poor correlation between morpholino
      induced and mutant phenotypes. Using CRISPR/Cas9-mediated mutagenesis, we
      generated a defined deletion eliminating the entire open reading frames of dlx3b
      and dlx4b (dlx3b/4b) and investigated a potential phenotypic difference between
      mutants and morpholino-mediated knockdown. Consistent with previous findings
      obtained by morpholino-mediated knockdown of Dlx3b and Dlx4b, dlx3b/4b mutants
      display compromised otic induction, the development of smaller otic vesicles and
      an elimination of all indications of otic specification when combined with loss
      of foxi1, a second known OEPD competence factor in zebrafish. Furthermore,
      sensorigenesis is also affected in dlx3b/4b mutants. However, we find that only
      early-born sensory hair cells (tether cells), that seed and anchor the formation
      of otoliths, are affected. Later-forming sensory hair cells are present,
      indicating that two genetically distinct pathways control the development of
      early-born and later-forming sensory hair cells. Finally, impairment of early
      born sensory hair cell formation in dlx3b/4b mutant embryos reverses the common
      temporal sequence of neuronal and sensory hair cell specification in zebrafish,
      resembling the order of cell specification in amniotes; Neurog1 expression before
      Atoh1 expression. We conclude that the Dlx3b/4b-dependent pathway has been either
      acquired newly in the fish lineage or lost in other vertebrate species during
      evolution, and that the events during early inner ear development are remarkably
      similar in fish and amniotes in the absence of this pathway.

PMID- 28751307
TI  - EsGLUT4 and CHHBP are involved in the regulation of glucose homeostasis in the
      crustacean Eriocheir sinensis.
AB  - Glucose is an essential energy source for both vertebrates and invertebrates. In
      mammals, glucose uptake is mediated primarily by glucose transporters (GLUTs),
      members of the major facilitator superfamily (MFS) of passive transporters. Among
      the GLUTs, GLUT4 is the main glucose transporter in muscles and adipocytes. In
      skeletal muscle cells, GLUT4 interacts with the lipid raft protein flotillin to
      transport glucose upon stimulation by insulin. Although several studies have
      examined GLUT4 function in mammals, few have been performed in crustaceans, which
      also use glucose as their main energy source. Crustacean hyperglycemic hormone
      (CHH) is a multifunctional neurohormone found only in arthropods, and one of its
      roles is to regulate glucose homeostasis. However, the molecular mechanism that
      underlies CHH regulation and whether GLUT4 is involved in its regulation in
      crustaceans remain unclear. In the present study, we identified a full-length
      GLUT4 cDNA sequence (defined herein as EsGLUT4) from the Chinese mitten crab
      Eriocheir sinensis and analyzed its tissue distribution and cellular
      localization. By the ForteBio Octet system, two large hydrophilic regions within
      EsGLUT4 were found to interact with the CHH binding protein (CHHBP), an E.
      sinensis flotillin-like protein. Interestingly, live-cell imaging indicated that
      EsGLUT4 and CHHBP responded simultaneously upon stimulation by CHH, resulting in
      glucose release. In contrast to insulin-dependent GLUT4, however, EsGLUT4 and
      CHHBP were present within cytoplasmic vesicles, both translocating to the plasma
      membrane upon CHH stimulation. In conclusion, our results provide new evidence
      for the involvement of EsGLUT4 and CHHBP in the regulation of glucose homeostasis
      in crustacean carbohydrate metabolism.

PMID- 28751308
TI  - The probability of wing damage in the dragonfly Sympetrum vulgatum (Anisoptera:
      Libellulidae): a field study.
AB  - Dragonfly wings resist millions of cycles of dynamic loading in their lifespan.
      During their operation, the wings are subjected to relatively high mechanical
      stresses. They further experience accidental collisions which result from the
      insects' daily activities, such as foraging, mating and fighting with other
      individuals. All these factors may lead to irreversible wing damage. Here, for
      the first time, we collected qualitative and quantitative data to systematically
      investigate the occurrence of damage in dragonfly wings in nature. The results
      obtained from the analysis of 119 wings from >30 individual Sympetrum vulgatum
      (Anisoptera: Libellulidae), collected at the second half of their flight period,
      indicate a high risk of damage in both fore- and hindwings. Statistical analyses
      show no significant difference between the extent of damage in fore- and
      hindwings, or between male and female dragonflies. However, we observe a
      considerable difference in the probability of damage in different wing regions.
      The wing damage is found to mainly result from two failure modes: wear and
      fracture.

PMID- 28751309
TI  - Fat-containing cells are eliminated during Dictyostelium development.
AB  - Triacylglycerol is a universal storage molecule for metabolic energy in living
      organisms. However, Dictyostelium amoebae, that have accumulated storage fat from
      added fatty acids do not progress through the starvation period preceding the
      development of the durable spore. Mutants deficient in genes of fat metabolism,
      such as fcsA, encoding a fatty acid activating enzyme, or dgat1 and dgat2,
      specifying proteins that synthesize triacylglycerol, strongly increase their
      chances to contribute to the spore fraction of the developing fruiting body, but
      lose the ability to produce storage fat efficiently. Dictyostelium seipin, an
      orthologue of a human protein that in patients causes the complete loss of
      adipose tissue when mutated, does not quantitatively affect fat storage in the
      amoeba. Dictyostelium seiP knockout mutants have lipid droplets that are enlarged
      in size but reduced in number. These mutants are as vulnerable as the wild type
      when exposed to fatty acids during their vegetative growth phase, and do not
      efficiently enter the spore head in Dictyostelium development.

PMID- 28751310
TI  - Standard metabolic rate predicts growth trajectory of juvenile Chinese crucian
      carp (Carassius auratus) under changing food availability.
AB  - Phenotypic traits vary greatly within populations and can have a significant
      influence on aspects of performance. The present study aimed to investigate the
      effects of individual variation in standard metabolic rate (SMR) on growth rate
      and tolerance to food deprivation in juvenile Chinese crucian carp (Carassius
      auratus) under varying levels of food availability. To address this issue, 19
      high and 16 low SMR individuals were randomly assigned to a satiation diet for 3
      weeks, whereas another 20 high and 16 low SMR individuals were assigned to a
      restricted diet (approximately 50% of satiation) for the same period. Then, all
      fish were completely food-deprived for another 3 weeks. High SMR individuals
      showed a higher growth rate when fed to satiation, but this advantage of SMR did
      not exist in food-restricted fish. This result was related to improved feeding
      efficiency with decreased food intake in low SMR individuals, due to their low
      food processing capacity and maintenance costs. High SMR individuals experienced
      more mass loss during food deprivation as compared to low SMR individuals. Our
      results here illustrate context-dependent costs and benefits of intraspecific
      variation in SMR whereby high SMR individuals show increased growth performance
      under high food availability but had a cost under stressful environments (i.e.
      food shortage).

PMID- 28751311
TI  - Identification of a novel population of highly cytotoxic c-Met-expressing CD8+ T
      lymphocytes.
AB  - CD8+ cytotoxic T lymphocytes (CTLs) are critical mediators of anti-tumor
      immunity, and controlling the mechanisms that govern CTL functions could be
      crucial for enhancing patient outcome. Previously, we reported that hepatocyte
      growth factor (HGF) limits effective murine CTL responses via antigen-presenting
      cells. Here, we show that a fraction of murine effector CTLs expresses the HGF
      receptor c-Met (c-Met+ CTLs). Phenotypic and functional analysis of c-Met+ CTLs
      reveals that they display enhanced cytolytic capacities compared to their c-Met-
      CTL counterparts. Furthermore, HGF directly restrains the cytolytic function of c
      Met+ CTLs in cell-mediated cytotoxicity reactions in vitro and in vivo and
      abrogates T-cell responses against metastatic melanoma in vivo Finally, we
      establish in three murine tumor settings and in human melanoma tissues that c
      Met+ CTLs are a naturally occurring CD8+ T-cell population. Together, our
      findings suggest that the HGF/c-Met pathway could be exploited to control CD8+ T
      cell-mediated anti-tumor immunity.

PMID- 28751312
TI  - A Dynamic Hydro-Mechanical and Biochemical Model of Stomatal Conductance for C4
      Photosynthesis.
AB  - C4 plants are major grain (maize [Zea mays] and sorghum [Sorghum bicolor]), sugar
      (sugarcane [Saccharum officinarum]), and biofuel (Miscanthus spp.) producers and
      contribute ~20% to global productivity. Plants lose water through stomatal pores
      in order to acquire CO2 (assimilation [A]) and control their carbon-for-water
      balance by regulating stomatal conductance (gS). The ability to mechanistically
      predict gS and A in response to atmospheric CO2, water availability, and time is
      critical for simulating stomatal control of plant-atmospheric carbon and water
      exchange under current, past, or future environmental conditions. Yet, dynamic
      mechanistic models for gS are lacking, especially for C4 photosynthesis. We
      developed and coupled a hydromechanical model of stomatal behavior with a
      biochemical model of C4 photosynthesis, calibrated using gas-exchange
      measurements in maize, and extended the coupled model with time-explicit
      functions to predict dynamic responses. We demonstrated the wider applicability
      of the model with three additional C4 grass species in which interspecific
      differences in stomatal behavior could be accounted for by fitting a single
      parameter. The model accurately predicted steady-state responses of gS to light,
      atmospheric CO2 and oxygen, soil drying, and evaporative demand as well as
      dynamic responses to light intensity. Further analyses suggest that the effect of
      variable leaf hydraulic conductance is negligible. Based on the model, we derived
      a set of equations suitable for incorporation in land surface models. Our model
      illuminates the processes underpinning stomatal control in C4 plants and suggests
      that the hydraulic benefits associated with fast stomatal responses of C4 grasses
      may have supported the evolution of C4 photosynthesis.

PMID- 28751313
TI  - 5-Aminolevulinic Acid Dehydratase Gene Dosage Affects Programmed Cell Death and
      Immunity.
AB  - Programmed cell death (PCD) is an important form to protect plants from pathogen
      attack. However, plants must precisely control the PCD process under microbe
      attacks to avoid detrimental effects. The complexity of how plants balance the
      defense activation and PCD requires further clarification. Lesion mimic mutants
      constitute an excellent material to study the crosstalk between them. Here, we
      identified a Gossypium hirsutum (cotton) lesion mimic mutant (Ghlmm), which
      exhibits necrotic leaf damage and enhanced disease resistance. Map-based cloning
      demonstrated that GhLMMD, encoding 5-aminolevulinic acid dehydratase and located
      on chromosome D5, was responsible for the phenotype. The mutant was resulted from
      a nonsense mutation within the coding region of GhLMMD It exhibited an
      overaccumulation of the 5-aminolevulinic acid, elevated levels of reactive oxygen
      species and salicylic acid, along with constitutive expression of pathogenesis
      related genes and enhanced resistance to the Verticillium dahliae infection.
      Interestingly, GhLMM plays a dosage-dependent role in regulating PCD of cotton
      leaves and resistance to V. dahliae infection. This study provides a new strategy
      on the modulation of plant immunity, particularly in polyploidy plants.

PMID- 28751314
TI  - Biosynthesis of Diterpenoids in Tripterygium Adventitious Root Cultures.
AB  - Adventitious root cultures were developed from Tripterygium regelii, and growth
      conditions were optimized for the abundant production of diterpenoids, which can
      be collected directly from the medium. An analysis of publicly available
      transcriptome data sets collected with T. regelii roots and root cultures
      indicated the presence of a large gene family (with 20 members) for terpene
      synthases (TPSs). Nine candidate diterpene synthase genes were selected for
      follow-up functional evaluation, of which two belonged to the TPS-c, three to the
      TPS-e/f, and four to the TPS-b subfamilies. These genes were characterized by
      heterologous expression in a modular metabolic engineering system in Escherichia
      coli Members of the TPS-c subfamily were characterized as copalyl diphosphate
      (diterpene) synthases, and those belonging to the TPS-e/f subfamily catalyzed the
      formation of precursors of kaurane diterpenoids. The TPS-b subfamily encompassed
      genes coding for enzymes involved in abietane diterpenoid biosynthesis and others
      with activities as monoterpene synthases. The structural characterization of
      diterpenoids accumulating in the medium of T. regelii adventitious root cultures,
      facilitated by searching the Spektraris online spectral database, enabled us to
      formulate a biosynthetic pathway for the biosynthesis of triptolide, a
      diterpenoid with pharmaceutical potential. Considering the significant enrichment
      of diterpenoids in the culture medium, fast-growing adventitious root cultures
      may hold promise as a sustainable resource for the large-scale production of
      triptolide.

PMID- 28751315
TI  - SCYL2 Genes Are Involved in Clathrin-Mediated Vesicle Trafficking and Essential
      for Plant Growth.
AB  - Protein transport between organelles is an essential process in all eukaryotic
      cells and is mediated by the regulation of processes such as vesicle formation,
      transport, docking, and fusion. In animals, SCY1-LIKE2 (SCYL2) binds to clathrin
      and has been shown to play roles in trans-Golgi network-mediated clathrin-coated
      vesicle trafficking. Here, we demonstrate that SCYL2A and SCYL2B, which are
      Arabidopsis (Arabidopsis thaliana) homologs of animal SCYL2, are vital for plant
      cell growth and root hair development. Studies of the SCYL2 isoforms using
      multiple single or double loss-of-function alleles show that SCYL2B is involved
      in root hair development and that SCYL2A and SCYL2B are essential for plant
      growth and development and act redundantly in those processes. Quantitative
      reverse transcription-polymerase chain reaction and a beta-glucuronidase-aided
      promoter assay show that SCYL2A and SCYL2B are differentially expressed in
      various tissues. We also show that SCYL2 proteins localize to the Golgi, trans
      Golgi network, and prevacuolar compartment and colocalize with Clathrin Heavy
      Chain1 (CHC1). Furthermore, bimolecular fluorescence complementation and
      coimmunoprecipitation data show that SCYL2B interacts with CHC1 and two Soluble
      NSF Attachment Protein Receptors (SNAREs): Vesicle Transport through t-SNARE
      Interaction11 (VTI11) and VTI12. Finally, we present evidence that the root hair
      tip localization of Cellulose Synthase-Like D3 is dependent on SCYL2B. These
      findings suggest the role of SCYL2 genes in plant cell developmental processes
      via clathrin-mediated vesicle membrane trafficking.

PMID- 28751318
TI  - Dysphagia and choking in an older man.

PMID- 28751319
TI  - Seven days in medicine: 19-25 July 2017.

PMID- 28751317
TI  - POSITIVE REGULATOR OF IRON HOMEOSTASIS1, OsPRI1, Facilitates Iron Homeostasis.
AB  - Oryza sativa HEMERYTHRIN MOTIF-CONTAINING REALLY INTERESTING NEW GENE AND ZINC
      FINGER PROTEIN1 (OsHRZ1) is a putative iron-binding sensor. However, it is
      unclear how OsHRZ1 transmits signals. In this study, we reveal that POSITIVE
      REGULATOR OF IRON HOMEOSTASIS1 (OsPRI1) interacts with OsHRZ1. A loss-of-function
      mutation to OsPRI1 increased the sensitivity of plants to Fe-deficient conditions
      and down-regulated the expression of Fe-deficiency-responsive genes. Yeast one
      hybrid and electrophoretic mobility shift assay results suggested that OsPRI1
      binds to the OsIRO2 and OsIRO3 promoters. In vitro ubiquitination experiments
      indicated that OsPRI1 is ubiquitinated by OsHRZ1. Cell-free degradation assays
      revealed that the stability of OsPRI1 decreased in wild-type roots but increased
      in the hrz1-2 mutant, suggesting OsHRZ1 is responsible for the instability of
      OsPRI1. The hrz1-2 seedlings were insensitive to Fe-deficient conditions. When
      the pri1-1 mutation was introduced into hrz1-2 mutants, the pri1hrz1 double
      mutant was more sensitive to Fe deficiency than the hrz1-2 mutant. Additionally,
      the expression levels of Fe-deficiency-responsive genes were lower in the
      hrz1pri1 double mutant than in the hrz1-2 mutant. Collectively, these results
      imply that OsPRI1, which is ubiquitinated by OsHRZ1, mediates rice responses to
      Fe deficiency by positively regulating OsIRO2 and OsIRO3 expression as part of
      the OsHRZ1-OsPRI1-OsIRO2/3 signal transduction cascade.

PMID- 28751316
TI  - Determining the Site of Action of Strigolactones during Nodulation.
AB  - Strigolactones (SLs) influence the ability of legumes to associate with nitrogen
      fixing bacteria. In this study, we determine the precise stage at which SLs
      influence nodulation. We show that SLs promote infection thread formation, as a
      null SL-deficient pea (Pisum sativum) mutant forms significantly fewer infection
      threads than wild-type plants, and this reduction can be overcome by the
      application of the synthetic SL GR24. We found no evidence that SLs influence
      physical events in the plant before or after infection thread formation, since SL
      deficient plants displayed a similar ability to induce root hair curling in
      response to rhizobia or Nod lipochitooligosaccharides (LCOs) and SL-deficient
      nodules appear to fix nitrogen at a similar rate to those of wild-type plants. In
      contrast, an SL receptor mutant displayed no decrease in infection thread
      formation or nodule number, suggesting that SL deficiency may influence the
      bacterial partner. We found that this influence of SL deficiency was not due to
      altered flavonoid exudation or the ability of root exudates to stimulate
      bacterial growth. The influence of SL deficiency on infection thread formation
      was accompanied by reduced expression of some early nodulation genes.
      Importantly, SL synthesis is down-regulated by mutations in genes of the Nod LCO
      signaling pathway, and this requires the downstream transcription factor NSP2 but
      not NIN This, together with the fact that the expression of certain SL
      biosynthesis genes can be elevated in response to rhizobia/Nod LCOs, suggests
      that Nod LCOs may induce SL biosynthesis. SLs appear to influence nodulation
      independently of ethylene action, as SL-deficient and ethylene-insensitive double
      mutant plants display essentially additive phenotypes, and we found no evidence
      that SLs influence ethylene synthesis or vice versa.

PMID- 28751320
TI  - Hypogonadism with Normal Serum Testosterone.

PMID- 28751321
TI  - Commentary.

PMID- 28751322
TI  - Commentary.

PMID- 28751323
TI  - A Case of Severe Neonatal Hyperammonemia.

PMID- 28751324
TI  - A Primed Hemoglobinopathy Screen.

PMID- 28751325
TI  - Julia.

PMID- 28751326
TI  - The Perseverance of Paul Cezanne.

PMID- 28751327
TI  - The Mind Gap.

PMID- 28751328
TI  - Health care in hard times: holding the line.

PMID- 28751329
TI  - Reimagining mental health in primary care: a blueprint for STPs.

PMID- 28751330
TI  - Dementia: is the biopsychosocial model vindicated?

PMID- 28751331
TI  - Communicating risk in primary care: what the Academy of Medical Sciences' report
      means in practice.

PMID- 28751332
TI  - Multidisciplinary care.

PMID- 28751333
TI  - Bad Medicine: Defensiveness.

PMID- 28751334
TI  - Gluten-free food prescriptions for children with coeliac disease: should families
      have to pay?

PMID- 28751335
TI  - Increased survival means increasing roles for primary care after cancer
      diagnosis.

PMID- 28751336
TI  - The Trump budget: what does it mean for global health?

PMID- 28751337
TI  - Marathon madness: important lessons learned.

PMID- 28751338
TI  - Time to revive the GP-focused clinical examination.

PMID- 28751339
TI  - Yonder: Adolescent asthma, termination of pregnancy, oncologists, and doctors'
      attire.

PMID- 28751340
TI  - Making a difference: working at Freedom from Torture.

PMID- 28751341
TI  - Bad Medicine: The medical untouchables.

PMID- 28751342
TI  - BJGP Library: Human Traces: An Alternative View of Mental Health.

PMID- 28751343
TI  - Exhibition: Raphael: The Drawings: Drawing Master.

PMID- 28751344
TI  - Exhibition: Sea of Hull: Turning Blue in Hull.

PMID- 28751345
TI  - Books: Night Shift: Dragons of Depression to Seabirds.

PMID- 28751346
TI  - Books: Dismembered: How the Attack on the State Harms Us All: Slash and Burn.

PMID- 28751347
TI  - Ageing meets unequal population.

PMID- 28751348
TI  - Early intervention in psychosis services.

PMID- 28751349
TI  - Challenges and pitfalls of antipsychotic prescribing in people with learning
      disability.

PMID- 28751350
TI  - Achieving a balance between the physical and the psychological in headache.

PMID- 28751351
TI  - Intrusive thoughts and images of intentional harm to infants in the context of
      maternal postnatal depression, anxiety, and OCD.

PMID- 28751352
TI  - Ultrasound-guided injections in primary care: evidence, costs, and suggestions
      for change.

PMID- 28751353
TI  - CMML/JMML PDXs: as easy as 1, 2, NSG-SGM3.

PMID- 28751354
TI  - R-CHOP in NLPHL: who should receive it?

PMID- 28751355
TI  - A novel role for p53 in self-tolerance.

PMID- 28751356
TI  - SOX11 holds mantle cell lymphoma's key to home.

PMID- 28751357
TI  - KRASG12D, pulmonary LCH, and atorvastatin.

PMID- 28751358
TI  - Hot therapy for cold agglutinin disease.

PMID- 28751359
TI  - Microbiome influences von Willebrand factor.

PMID- 28751360
TI  - Morphologic features of MU-heavy-chain disease.

PMID- 28751361
TI  - A rare case of autoimmune hemolytic anemia.

PMID- 28751362
TI  - Parkinson's disease: summary of updated NICE guidance.

PMID- 28751363
TI  - Five-level emergency triage systems: variation in assessment of validity.
AB  - INTRODUCTION: Triage systems are scales developed to rate the degree of urgency
      among patients who arrive at EDs. A number of different scales are in use;
      however, the way in which they have been validated is inconsistent. Also, it is
      difficult to define a surrogate that accurately predicts urgency. This systematic
      review described reference standards and measures used in previous validation
      studies of five-level triage systems. METHODS: We searched PubMed, EMBASE and
      CINAHL to identify studies that had assessed the validity of five-level triage
      systems and described the reference standards and measures applied in these
      studies. Studies were divided into those using criterion validity (reference
      standards developed by expert panels or triage systems already in use) and those
      using construct validity (prognosis, costs and resource use). RESULTS: A total of
      57 studies examined criterion and construct validity of 14 five-level triage
      systems. Criterion validity was examined by evaluating (1) agreement between the
      assigned degree of urgency with objective standard criteria (12 studies), (2)
      overtriage and undertriage (9 studies) and (3) sensitivity and specificity of
      triage systems (7 studies). Construct validity was examined by looking at (4) the
      associations between the assigned degree of urgency and measures gauged in EDs
      (48 studies) and (5) the associations between the assigned degree of urgency and
      measures gauged after hospitalisation (13 studies). Particularly, among 46
      validation studies of the most commonly used triages (Canadian Triage and Acuity
      Scale, Emergency Severity Index and Manchester Triage System), 13 and 39 studies
      examined criterion and construct validity, respectively. CONCLUSION: Previous
      studies applied various reference standards and measures to validate five-level
      triage systems. They either created their own reference standard or used a
      combination of severity/resource measures.

PMID- 28751365
TI  - NHS director who was arrested on suspicion of voyeurism resigns.

PMID- 28751366
TI  - Recent advances in oxygen sensing and signal transduction in hypoxic pulmonary
      vasoconstriction.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is a physiological reaction, which
      adapts lung perfusion to regional ventilation and optimizes gas exchange.
      Impaired HPV may cause systemic hypoxemia, while generalized HPV contributes to
      the development of pulmonary hypertension. The triggering mechanisms underlying
      HPV are still not fully elucidated. Several hypotheses are currently under
      debate, including a possible decrease as well as an increase in reactive oxygen
      species as a triggering event. Recent findings suggest an increase in the
      production of reactive oxygen species in pulmonary artery smooth muscle cells by
      complex III of the mitochondrial electron transport chain and occurrence of
      oxygen sensing at complex IV. Other essential components are voltage-dependent
      potassium and possibly L-type, transient receptor potential channel 6, and
      transient receptor potential vanilloid 4 channels. The release of arachidonic
      acid metabolites appears also to be involved in HPV regulation. Further
      investigation of the HPV mechanisms will facilitate the development of novel
      therapeutic strategies for the treatment of HPV-related disorders.

PMID- 28751364
TI  - Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors and
      modulate transcriptional activity.
AB  - Nuclear hormone receptors (NRs) regulate physiology by sensing lipophilic ligands
      and adapting cellular transcription appropriately. A growing understanding of the
      impact of circadian clocks on mammalian transcription has sparked interest in the
      interregulation of transcriptional programs. Mammalian clocks are based on a
      transcriptional feedback loop featuring the transcriptional activators circadian
      locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1),
      and transcriptional repressors cryptochrome (CRY) and period (PER). CRY1 and CRY2
      bind independently of other core clock factors to many genomic sites, which are
      enriched for NR recognition motifs. Here we report that CRY1/2 serve as
      corepressors for many NRs, indicating a new facet of circadian control of NR
      mediated regulation of metabolism and physiology, and specifically contribute to
      diurnal modulation of drug metabolism.

PMID- 28751368
TI  - Functional correlates of detailed body composition in healthy elderly subjects.
AB  - Methods of body composition analysis are now widely used to characterize health
      status, i.e., nutritional status, metabolic rates, and cardiometabolic risk
      factors. However, the functional correlates of individual body components have
      not been systematically analyzed. In this study, we have used a two-compartment
      model, which was assessed by air displacement plethysmography. Detailed body
      composition was measured by whole body magnetic resonance imaging in a healthy
      population of 40 Caucasians, aged 65-81 yr (20 men; body mass index range: 18.6
      37.2 kg/m2). Physical, metabolic, as well as endocrine functions included
      pulmonary function, handgrip strength, gait speed, sit-to-stand test, physical
      activity, blood pressure, body temperature, resting energy expenditure (REE),
      liver and kidney functions (glomerular filtration rate), insulin sensitivity
      [homeostasis model assessment (HOMA)], plasma lipids, plasma leptin,
      testosterone, dehydroepiandrosterone, insulin-like growth factor I levels,
      thyroid status, vitamins, and inflammation. Individual body compartments were
      intercorrelated, e.g., skeletal muscle mass (SM) correlated with visceral adipose
      tissue ( r = 0.53) and kidneys ( r = 0.62). For the functional correlates, SM ( r
      = 0.58) and liver volume ( r = 0.63) were associated with REE, SM correlated with
      handgrip strength ( r = 0.57), and kidneys with glomerular filtration rate ( r =
      0.57). While visceral adipose tissue correlated with HOMA ( r = 0.59),
      subcutaneous adipose tissue was related to plasma leptin levels ( r = 0.84). The
      subcutaneous adipose tissue-to-leptin relationship was moderated by inflammation
      increasing the explained variance of leptin levels by 4.0%. In linear regression
      analysis, detailed body composition explained variances in REE (75.0%), HOMA
      (41.0%), and leptin (78.0%) compared with a body mass index-based model (REE
      16.0%, HOMA 31.0%, leptin 45.0%). In addition, detailed body composition
      explained 39.0% of the variance in kidney function. NEW & NOTEWORTHY BCA should
      be used to address specific body functions only. In clinical practice, there is
      need of a clear focus on the specific research question related to physical,
      metabolic, or endocrine functions.

PMID- 28751369
TI  - Wearable technology for compensatory reserve to sense hypovolemia.
AB  - Traditional monitoring technologies fail to provide accurate or early indications
      of hypovolemia-mediated extremis because physiological systems (as measured by
      vital signs) effectively compensate until circulatory failure occurs. Hypovolemia
      is the most life-threatening physiological condition associated with circulatory
      shock in hemorrhage or sepsis, and it impairs one's ability to sustain physical
      exertion during heat stress. This review focuses on the physiology underlying the
      development of a novel noninvasive wearable technology that allows for real-time
      evaluation of the cardiovascular system's ability to compensate to hypovolemia,
      or its compensatory reserve, which provides an individualized estimate of
      impending circulatory collapse. Compensatory reserve is assessed by real-time
      changes (sampled millions of times per second) in specific features (hundreds of
      features) of arterial waveform analog signals that can be obtained from
      photoplethysmography using machine learning and feature extraction techniques.
      Extensive experimental evidence employing acute reductions in central blood
      volume (using lower-body negative pressure, blood withdrawal, heat stress,
      dehydration) demonstrate that compensatory reserve provides the best indicator
      for early and accurate assessment for compromises in blood pressure, tissue
      perfusion, and oxygenation in resting human subjects. Engineering challenges
      exist for the development of a ruggedized wearable system that can measure
      signals from multiple sites, improve signal-to-noise ratios, be customized for
      use in austere conditions (e.g., battlefield, patient transport), and be worn
      during strenuous physical activity.

PMID- 28751367
TI  - Imaging approaches to understand disease complexity: chronic obstructive
      pulmonary disease as a clinical model.
AB  - The clinical manifestations of chronic obstructive pulmonary disease (COPD)
      reflect an aggregate of multiple pulmonary and extrapulmonary processes. It is
      increasingly clear that full assessment of these processes is essential to
      characterize disease burden and to tailor therapy. Medical imaging has advanced
      such that it is now possible to obtain in vivo insight in the presence and
      severity of lung disease-associated features. In this review, we have assembled
      data from multiple disciplines of medical imaging research to review the role of
      imaging in characterization of COPD. Topics include imaging of the lungs, body
      composition, and extrapulmonary tissue metabolism. The primary focus is on
      imaging modalities that are widely available in clinical care settings and that
      potentially contribute to describing COPD heterogeneity and enhance our insight
      in underlying pathophysiological processes and their structural and functional
      effects.

PMID- 28751370
TI  - Effects of different input pressure waveforms on the carotid sinus baroreflex
      mediated sympathetic arterial pressure response in rats.
AB  - Although the pulsatility of an input pressure is an important factor that
      determines the arterial baroreflex responses, whether the difference in the input
      waveforms can meaningfully affect the baroreflex function remains unknown. This
      study aimed to compare baroreflex responses between two distinct pressure
      waveforms: a forward saw wave (FSW) and a backward saw wave (BSW). In seven
      anesthetized rats, carotid sinus pressure was exposed to the FSW or the BSW with
      a mean of 120 mmHg, pulse pressure of 40 mmHg, and pulse frequency of 1 Hz.
      Changes in efferent sympathetic nerve activity (SNA) and arterial pressure (AP)
      during six consecutive saw wave trials (FSW1, BSW1, FSW2, BSW2, FSW3, and BSW3)
      were examined. The steady-state SNA value during FSW1 was 91.1 +/- 1.9%, which
      was unchanged during FSW2 and FSW3 but significantly increased during BSW1 (106.6
      +/- 3.4%, P < 0.01), BSW2 (110.6 +/- 2.5%, P < 0.01), and BSW3 (111.6 +/- 2.3%, P
      < 0.01). The steady-state AP value during FSW1 was 98.2 +/- 8.1 mmHg, which was
      unchanged during FSW2 and FSW3 but significantly increased during BSW1 (106.7 +/-
      7.4 mmHg, P < 0.01), BSW2 (105.6 +/- 7.8 mmHg, P < 0.01), and BSW3 (103.8 +/- 7.2
      mmHg, P < 0.05). In conclusion, the FSW was more effective than the BSW in
      reducing mean SNA and AP. The finding could be applied to designing an artificial
      pulsatile pressure such as that generated by left ventricular assist devices.NEW
      & NOTEWORTHY This study examined whether the waveforms of an input pressure alone
      can affect the baroreflex function by using a forward saw wave and a backward saw
      wave with the same mean pressure, pulse pressure, and pulse frequency. The
      forward saw wave was more effective than the backward saw wave in reducing
      sympathetic nerve activity and arterial pressure. The finding could be applied to
      designing an artificial pulsatile pressure such as that generated by left
      ventricular assist devices.

PMID- 28751371
TI  - Wearable knee health system employing novel physiological biomarkers.
AB  - Knee injuries and chronic disorders, such as arthritis, affect millions of
      Americans, leading to missed workdays and reduced quality of life. Currently,
      after an initial diagnosis, there are few quantitative technologies available to
      provide sensitive subclinical feedback to patients regarding improvements or
      setbacks to their knee health status; instead, most assessments are qualitative,
      relying on patient-reported symptoms, performance during functional tests, and
      physical examinations. Recent advances have been made with wearable technologies
      for assessing the health status of the knee (and potentially other joints) with
      the goal of facilitating personalized rehabilitation of injuries and care for
      chronic conditions. This review describes our progress in developing wearable
      sensing technologies that enable quantitative physiological measurements and
      interpretation of knee health status. Our sensing system enables longitudinal
      quantitative measurements of knee sounds, swelling, and activity context during
      clinical and field situations. Importantly, we leverage machine-learning
      algorithms to fuse the low-level signal and feature data of the measured time
      series waveforms into higher level metrics of joint health. This paper summarizes
      the engineering validation, baseline physiological experiments, and human subject
      studies-both cross-sectional and longitudinal-that demonstrate the efficacy of
      using such systems for robust knee joint health assessment. We envision our
      sensor system complementing and advancing present-day practices to reduce joint
      reinjury risk, to optimize rehabilitation recovery time for a quicker return to
      activity, and to reduce health care costs.

PMID- 28751372
TI  - Energy cost of running instability evaluated with wearable trunk accelerometry.
AB  - Maintaining stability under dynamic conditions is an inherent challenge to
      bipedal running. This challenge may impose an energetic cost (Ec) thus hampering
      endurance running performance, yet the underlying mechanisms are not clear.
      Wireless triaxial trunk accelerometry is a simple tool that could be used to
      unobtrusively evaluate these mechanisms. Here, we test a cost of instability
      hypothesis by examining the contribution of trunk accelerometry-based measures
      (triaxial root mean square, step and stride regularity, and sample entropy) to
      interindividual variance in Ec (J/m) during treadmill running. Accelerometry and
      indirect calorimetry data were collected concurrently from 30 recreational
      runners (16 men; 14 women) running at their highest steady-state running speed
      (80.65 +/- 5.99% Vo2max). After reducing dimensionality with factor analysis, the
      effect of dynamic stability features on Ec was evaluated using hierarchical
      multiple regression analysis. Three accelerometry-based measures could explain an
      additional 10.4% of interindividual variance in Ec after controlling for body
      mass, attributed to anteroposterior stride regularity (5.2%), anteroposterior
      root mean square ratio (3.2%), and mediolateral sample entropy (2.0%). Our
      results lend support to a cost of instability hypothesis, with trunk acceleration
      waveform signals that are 1) more consistent between strides anteroposterioly, 2)
      larger in amplitude variability anteroposterioly, and 3) more complex
      mediolaterally and are energetically advantageous to endurance running
      performance. This study shows that wearable trunk accelerometry is a useful tool
      for understanding the Ec of running and that running stability is important for
      economy in recreational runners. NEW & NOTEWORTHY This study evaluates and more
      directly lends support to a cost of instability hypothesis between runners.
      Moreover, this hypothesis was tested using a minimalist setup including a single
      triaxial trunk mounted accelerometer, with potential transferability to
      biomechanical and performance analyses in typical outdoor settings.

PMID- 28751373
TI  - Heat shock protein 90 contributes to cutaneous vasodilation through activating
      nitric oxide synthase in young male adults exercising in the heat.
AB  - While the mechanisms underlying the control of cutaneous vasodilation have been
      extensively studied, there remains a lack of understanding of the different
      factors that may modulate cutaneous perfusion during an exercise-induced heat
      stress. We evaluated the hypothesis that heat shock protein 90 (HSP90)
      contributes to the heat loss response of cutaneous vasodilation via the
      activation of nitric oxide synthase (NOS) during exercise in the heat. In 11
      young males (25 +/- 5 yr), cutaneous vascular conductance (CVC) was measured at
      four forearm skin sites that were continuously treated with 1) lactated Ringer
      solution (control), 2) NOS inhibition with 10 mM NG-nitro-l-arginine methyl ester
      (l-NAME), 3) HSP90 inhibition with 178 MUM geldanamycin, or 4) a combination of
      10 mM l-NAME and 178 MUM geldanamycin. Participants rested in a moderate heat
      stress (35 degrees C) condition for 70 min. Thereafter, they performed a 50-min
      bout of moderate-intensity cycling (~52% Vo2peak) followed by a 30-min recovery
      period. We showed that NOS inhibition attenuated CVC (~40-50%) relative to the
      control site during pre- and postexercise rest in the heat (P <= 0.05); however,
      no effect of HSP90 inhibition was observed (P > 0.05). During exercise, we
      observed an attenuation of CVC with the separate inhibition of NOS (~40-50%) and
      HSP90 (~15-20%) compared with control (both P <= 0.05). However, the effect of
      HSP90 inhibition was absent in the presence of the coinhibition of NOS (P >
      0.05). We show that HSP90 contributes to cutaneous vasodilation in young men
      exposed to the heat albeit during exercise only. We also show that the HSP90
      contribution is due to NOS-dependent mechanisms.NEW & NOTEWORTHY We show that
      heat shock protein 90 functionally contributes to the heat loss response of
      cutaneous vasodilation during exercise in the heat, and this response is mediated
      through the activation of nitric oxide synthase. Therefore, interventions that
      may activate heat shock protein 90 may facilitate an increase in heat dissipation
      through an augmentation of cutaneous perfusion. In turn, this may attenuate or
      reduce the increase in core temperature and therefore the level of heat strain.

PMID- 28751374
TI  - Associations between motor unit action potential parameters and surface EMG
      features.
AB  - The surface interference EMG signal provides some information on the neural drive
      to muscles. However, the association between neural drive to muscle and muscle
      activation has long been debated with controversial indications due to the
      unavailability of motor unit population data. In this study, we clarify the
      potential and limitations of interference EMG analysis to infer motor unit
      recruitment strategies with an experimental investigation of several concurrently
      active motor units and of the associated features of the surface EMG. For this
      purpose, we recorded high-density surface EMG signals during linearly increasing
      force contractions of the tibialis anterior muscle, up to 70% of maximal force.
      The recruitment threshold (RT), conduction velocity (MUCV), median frequency
      (MDFMU), and amplitude (RMSMU) of action potentials of 587 motor units from 13
      individuals were assessed and associated with features of the interference EMG.
      MUCV was positively associated with RT (R2 = 0.64 +/- 0.14), whereas MDFMU and
      RMSMU showed a weaker relation with RT (R2 = 0.11 +/- 0.11 and 0.39 +/- 0.24,
      respectively). Moreover, the changes in average conduction velocity estimated
      from the interference EMG predicted well the changes in MUCV (R2 = 0.71), with a
      strong association to ankle dorsiflexion force (R2 = 0.81 +/- 0.12). Conversely,
      both the average EMG MDF and RMS were poorly associated with motor unit
      recruitment. These results clarify the limitations of EMG spectral and amplitude
      analysis in inferring the neural strategies of muscle control and indicate that,
      conversely, the average conduction velocity could provide relevant information on
      these strategies.NEW & NOTEWORTHY The surface EMG provides information on the
      neural drive to muscles. However, the associations between EMG features and
      neural drive have been long debated due to unavailability of motor unit
      population data. Here, by using novel highly accurate decomposition of the EMG,
      we related motor unit population behavior to a wide range of voluntary forces.
      The results fully clarify the potential and limitation of the surface EMG to
      provide estimates of the neural drive to muscles.

PMID- 28751375
TI  - Automated full-range pressure-volume curves in mice and rats.
AB  - Pressure-volume (PV) curves constructed over the entire lung volume range can
      reliably detect functional changes in mouse models of lung diseases. In the
      present study, we constructed full-range PV curves in healthy and elastase
      treated mice using either a classic manually operated technique or an automated
      approach using a computer-controlled piston ventilator [flexiVent FX; Scientific
      Respiratory Equipment (SCIREQ), Montreal, Quebec, Canada]. On the day of the
      experiment, subjects were anesthetized, tracheotomized, and mechanically
      ventilated. Following an initial respiratory mechanics scan and degassing of the
      lungs with 100% O2, full-range PV curves were constructed using either the
      classic or the automated technique. In control mice, superimposable curves were
      obtained, and statistical equivalence was attained between the two methodologies.
      In the elastase-treated ones, where significant changes in respiratory mechanics
      and lung volumes were expected, very small differences were observed between the
      two techniques, and the criteria for statistical equivalence were met in two out
      of four parameters assessed. The automated technique was adapted to rats and used
      to estimate the functional residual capacity (FRC) by volume subtraction. This
      novel approach generated FRC estimates consistent with the literature, with added
      accuracy relative to the existing method in diseased subjects. In conclusion, the
      automated technique generated full-range PV curves that were equivalent or very
      close to those obtained with the classic method under physiological or severe
      pathological conditions. The automation facilitated some technical aspects of the
      procedure, eased its use across species, and helped derive a more accurate
      estimate of FRC in preclinical models of respiratory disease.NEW & NOTEWORTHY
      Partial and full-range pressure-volume (PV) curves are frequently used to
      characterize lung disease models. Whereas automated techniques exist to construct
      partial PV curves, a manually operated approach is classically employed to build
      the full-range ones. In this study, the full-range PV curve technique was
      automated using a computer-controlled piston ventilator. The automation
      simplified the technique, facilitated its extension to other species, and
      inspired a novel way of estimating the functional residual capacity in laboratory
      rodents.

PMID- 28751376
TI  - Kinetic analyses of single-stranded break repair by human DNA ligase III isoforms
      reveal biochemical differences from DNA ligase I.
AB  - Humans have three genes encoding DNA ligases with conserved structural features
      and activities, but they also have notable differences. The LIG3 gene encodes a
      ubiquitous isoform in all tissues (LIG3alpha) and a germ line-specific splicing
      isoform (LIG3beta) that differs in the C-terminal domain. Both isoforms are found
      in the nucleus and the mitochondria. Here, we determined the kinetics and
      thermodynamics of single-stranded break ligation by LIG3alpha and LIG3beta and
      compared this framework to that of LIG1, the nuclear replicative ligase. The
      kinetic parameters of the LIG3 isoforms are nearly identical under all tested
      conditions, indicating that the BRCA1 C terminal (BRCT) domain specific to
      LIG3alpha does not alter ligation kinetics. Although LIG3 is only 22% identical
      to LIG1 across their conserved domains, the two enzymes had very similar maximal
      ligation rates. Comparison of the rate and equilibrium constants for LIG3 and
      LIG1 nevertheless revealed important differences. The LIG3 isoforms were seven
      times more efficient than LIG1 at ligating nicked DNA under optimal conditions,
      mainly because of their lower Km value for the DNA substrate. This could explain
      why LIG3 is less prone to abortive ligation than LIG1. Surprisingly, the affinity
      of LIG3 for Mg2+ was ten times weaker than that of LIG1, suggesting that Mg2+
      availability regulates DNA ligation in vivo, because Mg2+ levels are higher in
      the mitochondria than in the nucleus. The biochemical differences between the
      LIG3 isoforms and LIG1 identified here will guide the understanding of both
      unique and overlapping biological roles of these critical enzymes.

PMID- 28751377
TI  - A mosquito hemolymph odorant-binding protein family member specifically binds
      juvenile hormone.
AB  - Juvenile hormone (JH) is a key regulator of insect development and reproduction.
      In adult mosquitoes, it is essential for maturation of the ovary and normal male
      reproductive behavior, but how JH distribution and activity is regulated after
      secretion is unclear. Here, we report a new type of specific JH-binding protein,
      given the name mosquito juvenile hormone-binding protein (mJHBP), which
      circulates in the hemolymph of pupal and adult Aedes aegypti males and females.
      mJHBP is a member of the odorant-binding protein (OBP) family, and orthologs are
      present in the genomes of Aedes, Culex, and Anopheles mosquito species. Using
      isothermal titration calorimetry, we show that mJHBP specifically binds JH II and
      JH III but not eicosanoids or JH derivatives. mJHBP was crystallized in the
      presence of JH III and found to have a double OBP domain structure reminiscent of
      salivary "long" D7 proteins of mosquitoes. We observed that a single JH III
      molecule is contained in the N-terminal domain binding pocket that is closed in
      an apparent conformational change by a C-terminal domain-derived alpha-helix. The
      electron density for the ligand indicated a high occupancy of the natural 10R
      enantiomer of JH III. Of note, mJHBP is structurally unrelated to hemolymph JHBP
      from lepidopteran insects. A low level of expression of mJHBP in Ae. aegypti
      larvae suggests that it is primarily active during the adult stage where it could
      potentially influence the effects of JH on egg development, mating behavior,
      feeding, or other processes.

PMID- 28751378
TI  - Discovery of a microbial transglutaminase enabling highly site-specific labeling
      of proteins.
AB  - Microbial transglutaminases (MTGs) catalyze the formation of Gln-Lys isopeptide
      bonds and are widely used for the cross-linking of proteins and peptides in food
      and biotechnological applications (e.g. to improve the texture of protein-rich
      foods or in generating antibody-drug conjugates). Currently used MTGs have low
      substrate specificity, impeding their biotechnological use as enzymes that do not
      cross-react with nontarget substrates (i.e. as bio-orthogonal labeling systems).
      Here, we report the discovery of an MTG from Kutzneria albida (KalbTG), which
      exhibited no cross-reactivity with known MTG substrates or commonly used target
      proteins, such as antibodies. KalbTG was produced in Escherichia coli as soluble
      and active enzyme in the presence of its natural inhibitor ammonium to prevent
      potentially toxic cross-linking activity. The crystal structure of KalbTG
      revealed a conserved core similar to other MTGs but very short surface loops,
      making it the smallest MTG characterized to date. Ultra-dense peptide array
      technology involving a pool of 1.4 million unique peptides identified specific
      recognition motifs for KalbTG in these peptides. We determined that the motifs
      YRYRQ and RYESK are the best Gln and Lys substrates of KalbTG, respectively. By
      first reacting a bifunctionalized peptide with the more specific KalbTG and in a
      second step with the less specific MTG from Streptomyces mobaraensis, a
      successful bio-orthogonal labeling system was demonstrated. Fusing the KalbTG
      recognition motif to an antibody allowed for site-specific and ratio-controlled
      labeling using low label excess. Its site specificity, favorable kinetics, ease
      of use, and cost-effective production render KalbTG an attractive tool for a
      broad range of applications, including production of therapeutic antibody-drug
      conjugates.

PMID- 28751380
TI  - Complete Genome Sequence of Bradyrhizobium sp. ORS285, a Photosynthetic Strain
      Able To Establish Nod Factor-Dependent or Nod Factor-Independent Symbiosis with
      Aeschynomene Legumes.
AB  - Here, we report the complete genome sequence of Bradyrhizobium sp. strain ORS285,
      which is able to nodulate Aeschynomene legumes using two distinct strategies that
      differ in the requirement of Nod factors. The genome sequence information of this
      strain will help understanding of the different mechanisms of interaction of
      rhizobia with legumes.

PMID- 28751379
TI  - The interleukin-like epithelial-mesenchymal transition inducer ILEI exhibits a
      non-interleukin-like fold and is active as a domain-swapped dimer.
AB  - Production and secretion of pro-metastatic proteins is a feature of many tumor
      cells. The FAM3C interleukin-like epithelial-to-mesenchymal-transition (EMT)
      inducer (ILEI) has been shown to be strongly up-regulated in several cancers and
      to be essential for tumor formation and metastasis in epithelial cells,
      correlating with a significant decrease in overall survival in colon and breast
      cancer patients. ILEI has been seen to interact with the gamma-secretase
      presenilin 1 subunit (PS1). However, not much is known about the mechanism-of
      action or the detailed ILEI structure. We present here the crystal structures of
      FAM3C ILEI and show that it exists as monomers but also as covalent dimers. The
      observed ILEI beta-beta-alpha fold confirmed previous indications that the FAM3C
      proteins do not form classical four-helix-bundle structures as was initially
      predicted. This provides the first experimental evidence that the interleukin
      like EMT inducers are not evolutionarily related to the interleukins. However,
      more surprisingly, the ILEI dimer structure was found to feature a trans-linked
      domain swap, converting an intramolecular disulfide to intermolecular.
      Interestingly, dimeric but not monomeric ILEI was subsequently found to cause a
      dose-dependent increase in EpRas cell invasiveness comparable with TGF-beta,
      indicating that the dimer might be the active ILEI species. This is in line with
      a parallel study showing that covalent oligomerization of ILEI is essential for
      EMT and tumor progression in vivo The structures and the activity data give some
      first insight into the relationship between dimerization and ILEI function as
      well as indicate an intriguing link between ILEI, the PS1-protease, TGF-beta, and
      the TGF-beta receptor 1.

PMID- 28751381
TI  - Genome Sequence of Zymomonas mobilis subsp. mobilis NRRL B-1960.
AB  - Zymomonas mobilis subsp. mobilis is an efficient ethanol producer with
      application for industrial production of biofuel. To supplement existing Z.
      mobilis genomic resources and to facilitate genomic research, we used Oxford
      Nanopore and Illumina sequencing to assemble the complete genome of the beer
      spoilage isolate Z. mobilis subsp. mobilis strain NRRL B-1960.

PMID- 28751382
TI  - Draft Genome Sequence of Anoxybacillus sp. Strain UARK-01, a New Thermophilic
      Lignin-Utilizing Bacterium Isolated from Soil in Arkansas, USA.
AB  - The draft genome of Anoxybacillus sp. strain UARK-01, a novel lignin-utilizing
      thermophilic soil bacterium, represents the first sequence of an Anoxybacillus
      isolate from the United States. The genome was sequenced using the Illumina MiSeq
      platform, de novo assembled using SeqMan NGen, and annotated at NCBI. The genome
      sequence revealed genes for laccase and lignocellulose degradation enzymes.

PMID- 28751383
TI  - Complete Genome Sequence of Bacillus horikoshii Strain 20a from Cuatro Cienegas,
      Coahuila, Mexico.
AB  - We sequenced the Bacillus horikoshii 20a genome, isolated from sediment collected
      in Cuatro Cienegas, Mexico. We identified genes involved in establishing
      antagonistic interactions in microbial communities (antibiotic resistance and
      bacteriocins) and genes related to the metabolism of cyanophycin, a reserve
      compound and spore matrix material potentially relevant for survival in an
      oligotrophic environment.

PMID- 28751384
TI  - Analysis of an RNA-seq Strand-Specific Library Sample Reveals a Complete Genome
      of Hardenbergia mosaic virus from Native Wisteria, an Indigenous Virus from
      Southwest Australia.
AB  - Analysis of an RNA-seq strand-specific library revealed a complete genome of
      Hardenbergia mosaic virus (HarMV) from RNA extracted from a native wisteria
      (Hardenbergia comptoniana) plant from southwest Australia. We compared it with
      eight other complete HarMV genomes. It most resembled (85.8% nucleotide identity)
      the genome of HarMV isolate MD4-D.

PMID- 28751385
TI  - Identification of Dezidougou Virus in a DAK AR 41524 Zika Virus Stock.
AB  - We report here the complete genome of a Dezidougou virus (DEZV) isolated from a
      passaged culture of the Zika virus strain DAK AR 41524. The consensus DEZV
      sequence we recovered shows 99% nucleotide similarity using BLASTN to a
      previously reported DEZV (accession no. JQ675604.1). The current sequence has
      additional repeat regions as well as a deleted repeat region, which we confirmed
      by Sanger sequencing, that were not present in the originally published sequence,
      JQ675604.1.

PMID- 28751386
TI  - Genome Sequence of the Dichloromethane-Degrading Bacterium Hyphomicrobium sp.
      Strain GJ21.
AB  - The genome sequence of Hyphomicrobium sp. strain GJ21, isolated in the
      Netherlands from samples of environments contaminated with halogenated pollutants
      and capable of using dichloromethane as its sole carbon and energy source, was
      determined.

PMID- 28751387
TI  - Complete Genome Sequence of Kluyveromyces lactis Strain GG799, a Common Yeast
      Host for Heterologous Protein Expression.
AB  - We report the genome sequence of the dairy yeast Kluyveromyces lactis strain
      GG799 obtained using the Pacific Biosciences RS II platform. K. lactis strain
      GG799 is a common host for the expression of proteins at both laboratory and
      industrial scales.

PMID- 28751388
TI  - Rhizospheric Microbiome Profiling of Capsicum annuum L. Cultivated in Amended
      Soils by 16S and Internal Transcribed Spacer 2 rRNA Amplicon Metagenome
      Sequencing.
AB  - Rhizospheric microbiomes of Capsicum annuum L. cultivated either conventionally
      or amended with a synthetic microbial consortium or a root exudate inductor, were
      characterized by 16S/internal transcribed spacer 2 (ITS2) rRNA amplicon
      metagenome sequencing. The most abundant taxa found, although differently
      represented in each treatment, were Gammaproteobacteria, Alphaproteobacteria,
      Actinobacteria, and Bacilli, as well as Chytridiomycetes and Mortierellomycotina.

PMID- 28751389
TI  - First Complete Genome Sequence of Potato leafroll virus from Argentina.
AB  - In this study, we determined for the first time the complete genomic sequence of
      an Argentinian isolate of Potato leafroll virus (PLRV), the type species of the
      genus Polerovirus The isolate sequenced came from a Solanum tuberosum plant that
      had been naturally infected with the virus. Isolate PLRV-AR had a nucleotide
      sequence identity between 94.4 and 97.3% with several known PLRV isolates
      worldwide.

PMID- 28751390
TI  - Draft Genome Sequences of 43 Lactobacillus Strains from the Species L. curvatus,
      L. fermentum, L. paracasei, L. plantarum, L. rhamnosus, and L. sakei, Isolated
      from Food Products.
AB  - The genome sequences of 43 Lactobacillus strains from the species L. curvatus, L.
      fermentum, L. paracasei, L. plantarum, L. rhamnosus, and L. sakei were determined
      using Illumina MiSeq.

PMID- 28751391
TI  - Complete Genome Sequences of Eight Rhizobium Symbionts Associated with Common
      Bean (Phaseolus vulgaris).
AB  - We present here the high-quality complete genome sequences of eight strains of
      Rhizobium-nodulating Phaseolus vulgaris Comparative analyses showed that some of
      them belonged to different genomic and evolutionary lineages with common
      symbiotic properties. Two novel symbiotic plasmids (pSyms) with P. vulgaris
      specificity are reported here.

PMID- 28751392
TI  - Draft Genome Sequence of Rathayibacter sp. Strain VKM Ac-2630 Isolated from Leaf
      Gall Induced by the Knapweed Nematode Mesoanguina picridis on Acroptilon repens.
AB  - A draft genome sequence of Rathayibacter sp. strain VKM Ac-2630 was derived using
      Ion Torrent sequencing technology. The genome size of this strain is 3.88 Mb,
      with an average G+C content of 72.0%. Genomic evidence of an aerobic mode of
      respiration and a heterotrophic lifestyle of this bacterium was obtained.

PMID- 28751393
TI  - Genome Sequence of Leuconostoc mesenteroides LK-151 Isolated from a Japanese Sake
      Cellar as a High Producer of d-Amino Acids.
AB  - Here, we report the complete genome sequence of strain LK-151 of Leuconostoc
      mesenteroides, which was isolated from a Japanese sake cellar and has the
      potential to produce large amounts of d-amino acids, namely, d-Ala and d-Glu. The
      genome contains 4 genes related to d-amino acid production.

PMID- 28751394
TI  - Complete Genome Sequence of Pseudomonas viridiflava CFBP 1590, Isolated from
      Diseased Cherry in France.
AB  - Pseudomonas viridiflava causes foliar and stem necrosis, as well as stem and root
      rot on a wide range of plants. We report here the first complete genome of a P.
      viridiflava strain, isolated from diseased tissue of a cherry tree.

PMID- 28751395
TI  - Draft Genome Sequence of Terrimicrobium sacchariphilum NM-5T, a Facultative
      Anaerobic Soil Bacterium of the Class Spartobacteria.
AB  - We report here a high-quality draft genome sequence of Terrimicrobium
      sacchariphilum strain NM-5T, a facultative anaerobic, mesophilic, fermentative
      bacterium belonging to the class Spartobacteria of the phylum Verrucomicrobia The
      genome comprises 4,751,807 bp in three contigs and has a G+C content of 60.19%.
      Annotation predicted 4,175 protein-coding sequences and 54 RNAs.

PMID- 28751396
TI  - Novel RNA Virus Genome Discovered in Ghost Ants (Tapinoma melanocephalum) from
      Hawaii.
AB  - Here, we report the full-genome sequence of Milolii virus, a novel single
      stranded (positive-sense) RNA virus discovered from Tapinoma melanocephalum ants
      in Hawaii. The genome is 10,475 nucleotides long, encoding a polyprotein of 3,304
      amino acids.

PMID- 28751397
TI  - Genome Sequence of Ophidiomyces ophiodiicola, an Emerging Fungal Pathogen of
      Snakes.
AB  - Ophidiomyces ophiodiicola, which belongs to the order Onygenales, is an emerging
      fungal pathogen of snakes in the United States. This study reports the 21.9-Mb
      genome sequence of an isolate of this reptilian pathogen obtained from a black
      racer snake in Pennsylvania.

PMID- 28751398
TI  - Draft Genome Sequence of Enterococcus faecalis DD14, a Bacteriocinogenic Lactic
      Acid Bacterium with Anti-Clostridium Activity.
AB  - We report the draft genome sequence of Enterococcus faecalis DD14, a strain
      isolated from meconium of a healthy newborn at Roubaix Hospital (France). The
      strain displayed antagonism against a set of Gram-positive bacteria through
      concomitant production of lactic acid and bacteriocin. The genome has a size of
      2,893,365 bp and a 37.3% G+C ratio and is predicted to contain at least 2,755
      coding sequences and 62 RNAs.

PMID- 28751399
TI  - Complete Genome Sequence of Torque teno indri virus 1, a Novel Anellovirus in
      Blood from a Free-Living Lemur.
AB  - We identified Torque teno indri virus 1 (TTIV1), the first anellovirus in a free
      living lemur (Indri indri). The complete circular 2,572-nucleotide (nt) TTIV1
      genome is distantly related to torque teno sus virus. Phylogenetic and sequence
      analyses support TTIV1 as a putative member of a new genus within the
      Anelloviridae family.

PMID- 28751400
TI  - Complete Genome Sequence of the Sourdough Isolate Lactobacillus zymae ACA-DC
      3411.
AB  - Lactobacillus zymae is a Gram-positive lactic acid bacterium belonging to the
      Lactobacillus brevis clade. Here, we report the first complete genome sequence of
      L. zymae ACA-DC 3411, which was isolated from traditional Greek wheat sourdough.
      Whole-genome analysis may reveal adaptive traits of strain ACA-DC 3411 in the
      sourdough ecosystem.

PMID- 28751401
TI  - Genome Sequence of Pantoea sp. Strain 1.19, Isolated from Rice Rhizosphere, with
      the Capacity To Promote Growth of Legumes and Nonlegumes.
AB  - Pantoea sp. 1.19, a plant growth-promoting bacterium (PGPB), was isolated from
      the rhizosphere of rice plants in Spain. Its genome, estimated at 3,771,065 bp,
      encodes 3,535 coding sequences (CDSs), carrying genes for synthesis of auxins,
      homoserine lactones, enzymes, siderophores, and quorum sensing. Several CDSs
      emphasize its biotechnological potential as an agriculture inoculant.

PMID- 28751402
TI  - Whole-Genome Shotgun Sequences of Salmonella enterica Serovar Typhimurium
      Lilleengen Type Strains LT1, LT18, LT19, LT20, LT21, and LT22.
AB  - The Lilleengen type (LT) collection of Salmonella enterica serovar Typhimurium
      strains has served the scientific community as a group of model organisms for
      basic genetic and biochemical pathway research. Here, we report the whole-genome
      shotgun sequences of Salmonella enterica serovar Typhimurium strains LT1, LT18,
      LT19, LT20, LT21, and LT22.

PMID- 28751403
TI  - Draft Genome Sequence of Paenarthrobacter nicotinovorans Hce-1.
AB  - Paenarthrobacter nicotinovorans Hce-1 is a Gram-positive obligate aerobe
      actinomycete. We report here the complete genome sequence of this organism. The
      genome has a length of 4,174,362 bp and contains 4,568 protein-coding genes, 64
      tRNA operons, and 22 rRNA operons. Its GC content in the gene region is 63.4%.

PMID- 28751404
TI  - Microbiomes of American Oysters (Crassostrea virginica) Harvested from Two Sites
      in the Chesapeake Bay.
AB  - In this study, we used 16S rRNA gene amplicons to describe the bacterial
      microbiota associated with oysters (Crassostrea virginica) and seawater collected
      from two sites in the Chesapeake Bay. The dominant bacterial groups included
      those belonging to the order Pelagibacteraceae, family Enterobacteriaceae, and
      genus Synechococcus The microbiomes varied among oysters from the same site and
      between the two sites and months.

PMID- 28751405
TI  - Complete Genome Sequence of Vibrio gazogenes ATCC 43942.
AB  - Vibrio gazogenes ATCC 43942 has the potential to synthesize a plethora of
      metabolites which are of clinical and agricultural significance in response to
      environmental triggers. The complete genomic sequence of Vibrio gazogenes ATCC
      43942 is reported herein, contributing to the knowledge base of strains in the
      Vibrio genus.

PMID- 28751406
TI  - Draft Genome Sequence of Pseudomonas syringae PDD-32b-74, a Model Strain for Ice
      Nucleation Studies in the Atmosphere.
AB  - We report here the whole genome sequence of Pseudomonas syringae PDD-32b-74, a
      gammaproteobacterium isolated from cloud water. This microorganism is equipped
      with ice-nucleation protein and biosurfactant genes that could potentially be
      involved in physicochemical processes in the atmosphere and clouds.

PMID- 28751407
TI  - Complete Genome Sequence of Campylobacter jejuni subsp. jejuni ATCC 35925.
AB  - Here, we report the complete genome sequence of Campylobacter jejuni ATCC 35925,
      an avian isolate from Sweden. The genome gives insight into the ATCC 35925
      strain's remarkable ability to tolerate copper and its permissiveness to plasmid
      transformation.

PMID- 28751408
TI  - Draft Genome Sequences of Saccharibacter sp. Strains 3.A.1 and M18 Isolated from
      Honey and a Honey Bee (Apis mellifera) Stomach.
AB  - The annotated draft genome sequences of two recent Saccharibacter sp. strains
      isolated from honey and a honey bee stomach in 2014 are reported here. Currently,
      two Saccharibacter whole-genome sequences are available in databases; thus, the
      sequences of our new isolates will contribute to a better understanding of
      Saccharibacter genomes.

PMID- 28751410
TI  - Evaluating 17 years of latent tuberculosis infection screening in north-west
      England: a retrospective cohort study of reactivation.
AB  - Approximately 72% of tuberculosis (TB) cases in England occur among non-UK born
      individuals, mostly as a result of reactivation of latent TB infection (LTBI).
      Programmatic LTBI screening is a key intervention of the TB strategy for England.
      This article reviews the results of a long-standing LTBI screening initiative in
      England.A retrospective cohort was created through probabilistic linkage between
      LTBI screening data and national TB case notifications. Screened persons were
      followed until they died, became a case, emigrated or until cohort-end. TB
      incidence rates and rate ratios (IRR) were calculated.97 out of 1820 individuals
      screened for LTBI were reported to have active TB. Crude incidence rates among
      LTBI-positive, treatment-naive individuals were 4.1 and 2.3 per 100 person-years
      in the QuantiFERON and tuberculin skin test cohorts, respectively. Among the
      QuantiFERON cohort, Poisson regression showed that LTBI positivity (IRR 22.6, 95%
      CI 6.8-74.6) and no chemoprophylaxis increased the probability of becoming a TB
      case (IRR 0.17, 95% CI 0.05-0.6).We found high TB rates in LTBI-positive,
      treatment-naive individuals and a strong association between no treatment and
      becoming a TB case, demonstrating feasibility and effectiveness of LTBI screening
      and providing important policy lessons for LTBI screening in England and beyond.

PMID- 28751411
TI  - Effectiveness and safety of standardised shorter regimens for multidrug-resistant
      tuberculosis: individual patient data and aggregate data meta-analyses.
AB  - We assessed the effectiveness and safety of standardised, shorter multidrug
      resistant tuberculosis (MDR-TB) regimens by pooling data from observational
      studies.Published studies were identified from medical databases; unpublished
      studies were identified from expert consultation. We conducted aggregate data
      meta-analyses to estimate pooled proportions of treatment outcomes and individual
      patient data (IPD) meta-regression to identify risk factors for unsuccessful
      treatment in patients treated with 9- to 12-month MDR-TB regimens composed of a
      second-line injectable, gatifloxacin/moxifloxacin, prothionamide, clofazimine,
      isoniazid, pyrazinamide and ethambutol.We included five studies in which 796 out
      of 1279 (62.2%) individuals with confirmed MDR-TB (98.4%) or rifampin-resistant
      TB (1.6%), and not previously exposed to second-line drugs, were eligible for
      shorter regimens. 669 out of 796 participants were successfully treated (83.0%,
      95% CI 71.9-90.3%). In IPD meta-regression (three studies, n=497),
      failure/relapse was associated with fluoroquinolone resistance (crude OR 46, 95%
      CI 8-273), pyrazinamide resistance (OR 8, 95% CI 2-38) and no culture conversion
      by month 2 of treatment (OR 7, 95% CI 3-202). Two participants acquired extensive
      drug resistance. Four studies reported grade 3 or 4 adverse events in 55 out of
      304 (18.1%) participants.Shorter regimens were effective in treating MDR-TB;
      however, there is uncertainty surrounding the generalisability of the high rate
      of treatment success to less selected populations, to programmatic settings and
      in the absence of drug susceptibility tests to key component drugs.

PMID- 28751412
TI  - Risk of recurrent venous thromboembolism in COPD patients: results from a
      prospective cohort study.
AB  - We aimed to assess the risk of recurrent venous thromboembolism (VTE) in patients
      with chronic obstructive pulmonary disease (COPD) following cessation of
      anticoagulation therapy.In a prospective cohort of 1468 patients with a
      documented episode of VTE, followed for up to 5 years after cessation of
      anticoagulation therapy, the diagnosis of COPD was confirmed in 136. The main
      outcome was recurrent VTE. The secondary outcome was overall mortality.
      Univariate and multivariate analyses were performed to identify the risk factors
      of recurrence.Of the 1468 patients included, recurrent VTE was observed in 306
      (34 with COPD and 272 without) during a median follow-up period of 36.5 months.
      The incidence rate of recurrent VTE was 9.1% (95% CI 6.5-12.8) for COPD patients
      and 7.0% (95% CI 6.2-7.9) for non-COPD patients. COPD was not associated with an
      increased risk of VTE recurrence on univariate or multivariate analyses (hazard
      ratio: 1.0 (95% CI 0.7-1.4)). The risk of death, adjusted for demographic and
      clinical characteristics, showed no increase in COPD patients, as compared to non
      COPD patients.In patients with COPD who had an acute episode of VTE, the risk of
      recurrent VTE was not any higher than that in non-COPD patients.

PMID- 28751414
TI  - Lazarus syndrome in nonsmall cell lung cancer patients with poor performance
      status and major leukocytosis following nivolumab treatment.

PMID- 28751413
TI  - Long-term outcomes of dasatinib-induced pulmonary arterial hypertension: a
      population-based study.
AB  - This study aimed to describe the long-term outcomes of pulmonary arterial
      hypertension (PAH) induced by dasatinib.21 incident, right heart catheterisation
      confirmed cases of dasatinib-induced PAH were identified from the French
      Pulmonary Hypertension Registry. Clinical and haemodynamic variables were
      compared from baseline to last follow-up (median (range) 24 (1-81) months).Median
      age was 52 years and 15 patients were female (71%). 19 patients received
      dasatinib for chronic myelogenous leukaemia for a median (range) duration of 42
      (8-74) months before PAH diagnosis. No bone morphogenic protein receptor-2
      (BMPR2) mutations were found in the 10 patients tested. Dasatinib was uniformly
      discontinued and 11 patients received PAH medications. Four patients died during
      follow-up. New York Heart Association functional class improved from 76% in class
      III/IV to 90% in class I/II (p<0.01). Median (range) 6-min walk distance improved
      from 306 (0-660) to 430 (165-635) m (p<0.01). Median (range) mean pulmonary
      arterial pressure improved from 45 (30-70) to 26 (17-50) mmHg (p<0.01) and
      pulmonary vascular resistance from 6.1 (3.2-27.3) to 2.6 (1.2-5.9) Wood units
      (p<0.01). Patients treated with PAH medications had worse baseline haemodynamics
      but similar long-term outcomes to untreated patients. PAH persisted in 37% of
      patients.Dasatinib-induced PAH frequently improves after discontinuation but
      persisted in over one-third of patients, therefore systematic follow-up is
      essential.

PMID- 28751415
TI  - Early outcomes in MDR-TB and XDR-TB patients treated with delamanid under
      compassionate use.

PMID- 28751416
TI  - Excess economic burden of comorbidities in COPD: a 15-year population-based
      study.
AB  - A better understanding of the true burden of chronic obstructive pulmonary
      disease (COPD) needs to consider the implications of comorbidities. This study
      comprehensively examined the impact of comorbidities on excess direct medical
      costs in COPD patients.From health administrative data in British Columbia,
      Canada (1996-2012), we created a propensity-score-matched cohort of incident COPD
      patients and individuals without COPD. Health services use records were compiled
      into 16 major disease categories based on International Classification of
      Diseases codes. Excess costs (in 2015 Canadian dollars and converted to 2015
      Euros; CAD1.000=EUR 0.706) were estimated as the adjusted difference in direct
      medical costs between the two groups.The sample included 128 424 subjects in each
      group. COPD patients generated excess costs of CAD5196/EUR3668 per person-year
      (95% CI CAD3540-8529), of which 26% was attributable to COPD itself and 51% was
      attributable to comorbidities (the remaining 23% could not be attributed to any
      specific condition). The major cost driver was excess hospitalisation costs. The
      largest components of comorbidity costs were circulatory diseases, other
      respiratory disorders, digestive disorders and psychological disorders
      (CAD696/EUR491, CAD312/EUR220, CAD274/EUR193 and CAD249/EUR176 per person-year,
      respectively).These findings suggest that the prevention and appropriate
      management of comorbidities in COPD patients may effectively reduce the overall
      burden of COPD.

PMID- 28751417
TI  - Assessment of Burden of COPD tool: evidence not perception.

PMID- 28751418
TI  - Costly comorbidities of COPD: the ignored side of the coin?

PMID- 28751419
TI  - The paradoxical association between pulmonary embolism and COPD.

PMID- 28751420
TI  - Recombination-Driven Genome Evolution and Stability of Bacterial Species.
AB  - While bacteria divide clonally, horizontal gene transfer followed by homologous
      recombination is now recognized as an important contributor to their evolution.
      However, the details of how the competition between clonality and recombination
      shapes genome diversity remains poorly understood. Using a computational model,
      we find two principal regimes in bacterial evolution and identify two composite
      parameters that dictate the evolutionary fate of bacterial species. In the
      divergent regime, characterized by either a low recombination frequency or strict
      barriers to recombination, cohesion due to recombination is not sufficient to
      overcome the mutational drift. As a consequence, the divergence between pairs of
      genomes in the population steadily increases in the course of their evolution.
      The species lacks genetic coherence with sexually isolated clonal subpopulations
      continuously formed and dissolved. In contrast, in the metastable regime,
      characterized by a high recombination frequency combined with low barriers to
      recombination, genomes continuously recombine with the rest of the population.
      The population remains genetically cohesive and temporally stable. Notably, the
      transition between these two regimes can be affected by relatively small changes
      in evolutionary parameters. Using the Multi Locus Sequence Typing (MLST) data, we
      classify a number of bacterial species to be either the divergent or the
      metastable type. Generalizations of our framework to include selection,
      ecologically structured populations, and horizontal gene transfer of
      nonhomologous regions are discussed as well.

PMID- 28751421
TI  - The Recombination Landscape in Wild House Mice Inferred Using Population Genomic
      Data.
AB  - Characterizing variation in the rate of recombination across the genome is
      important for understanding several evolutionary processes. Previous analysis of
      the recombination landscape in laboratory mice has revealed that the different
      subspecies have different suites of recombination hotspots. It is unknown,
      however, whether hotspots identified in laboratory strains reflect the hotspot
      diversity of natural populations or whether broad-scale variation in the rate of
      recombination is conserved between subspecies. In this study, we constructed fine
      scale recombination rate maps for a natural population of the Eastern house
      mouse, Mus musculus castaneus We performed simulations to assess the accuracy of
      recombination rate inference in the presence of phase errors, and we used a novel
      approach to quantify phase error. The spatial distribution of recombination
      events is strongly positively correlated between our castaneus map, and a map
      constructed using inbred lines derived predominantly from M. m. domesticus
      Recombination hotspots in wild castaneus show little overlap, however, with the
      locations of double-strand breaks in wild-derived house mouse strains. Finally,
      we also find that genetic diversity in M. m. castaneus is positively correlated
      with the rate of recombination, consistent with pervasive natural selection
      operating in the genome. Our study suggests that recombination rate variation is
      conserved at broad scales between house mouse subspecies, but it is not strongly
      conserved at fine scales.

PMID- 28751422
TI  - Analysis of Large-Scale Mutagenesis Data To Assess the Impact of Single Amino
      Acid Substitutions.
AB  - Mutagenesis is a widely used method for identifying protein positions that are
      important for function or ligand binding. Advances in high-throughput DNA
      sequencing and mutagenesis techniques have enabled measurement of the effects of
      nearly all possible amino acid substitutions in many proteins. The resulting
      large-scale mutagenesis data sets offer a unique opportunity to draw general
      conclusions about the effects of different amino acid substitutions. Thus, we
      analyzed 34,373 mutations in 14 proteins whose effects were measured using large
      scale mutagenesis approaches. Methionine was the most tolerated substitution,
      while proline was the least tolerated. We found that several substitutions,
      including histidine and asparagine, best recapitulated the effects of other
      substitutions, even when the identity of the wild-type amino acid was considered.
      The effects of histidine and asparagine substitutions also correlated best with
      the effects of other substitutions in different structural contexts. Furthermore,
      highly disruptive substitutions like aspartic and glutamic acid had the most
      discriminatory power for detecting ligand interface positions. Our work
      highlights the utility of large-scale mutagenesis data, and our conclusions can
      help guide future single substitution mutational scans.

PMID- 28751423
TI  - SID-1 Functions in Multiple Roles To Support Parental RNAi in Caenorhabditis
      elegans.
AB  - Systemic RNA interference (RNAi) in Caenorhbaditis elegans requires sid-1, sid-3,
      and sid-5 Injected, expressed, or ingested double-stranded RNA (dsRNA) is
      transported between cells, enabling RNAi in most tissues, including the germline
      and progeny (parental RNAi). A recent report claims that parental RNAi also
      requires the yolk receptor rme-2 Here, we characterize the role of the sid genes
      and rme-2 in parental RNAi. We identify multiple independent paths for maternal
      dsRNA to reach embryos and initiate RNAi. We showed previously that maternal and
      embryonic sid-1 contribute independently to parental RNAi. Here we demonstrate a
      role for embryonic sid-5, but not sid-2 or sid-3 in parental RNAi. We also find
      that maternal rme-2 contributes to but is not required for parental RNAi. We
      determine that parental RNAi by feeding occurs nearly exclusively in adults. We
      also introduce 5-ethynyluridine to densely internally label dsRNA, avoiding
      complications associated with other labeling strategies such as inhibition of
      normal dsRNA trafficking and separation of label and RNA. Labeling shows that
      yolk and dsRNA do not colocalize following endocytosis, suggesting independent
      uptake, and, furthermore, dsRNA appears to rapidly progress through the RAB-7
      endocytosis pathway independently of sid-1 activity. Our results support the
      premise that although sid-1 functions in multiple roles, it alone is central and
      absolutely required for inheritance of silencing RNAs.

PMID- 28751424
TI  - A simple, cost-effective method for generating murine colonic 3D enteroids and 2D
      monolayers for studies of primary epithelial cell function.
AB  - Cancer cell lines have been the mainstay of intestinal epithelial experimentation
      for decades, due primarily to their immortality and ease of culture. However,
      because of the inherent biological abnormalities of cancer cell lines, many
      cellular biologists are currently transitioning away from these models and toward
      more representative primary cells. This has been particularly challenging, but
      recent advances in the generation of intestinal organoids have brought the
      routine use of primary cells within reach of most epithelial biologists.
      Nevertheless, even with the proliferation of publications that use primary
      intestinal epithelial cells, there is still a considerable amount of trial and
      error required for laboratories to establish a consistent and reliable method to
      culture three-dimensional (3D) intestinal organoids and primary epithelial
      monolayers. We aim to minimize the time other laboratories spend troubleshooting
      the technique and present a standard method for culturing primary epithelial
      cells. Therefore, we have described our optimized, high-yield, cost-effective
      protocol to grow 3D murine colonoids for more than 20 passages and our detailed
      methods to culture these cells as confluent monolayers for at least 14 days,
      enabling a wide variety of potential future experiments. By supporting and
      expanding on the current literature of primary epithelial culture optimization
      and detailed use in experiments, we hope to help enable the widespread adoption
      of these innovative methods and allow consistency of results obtained across
      laboratories and institutions.NEW & NOTEWORTHY Primary intestinal epithelial
      monolayers are notoriously difficult to maintain culture, even with the recent
      advances in the field. We describe, in detail, the protocols required to maintain
      three-dimensional cultures of murine colonoids and passage these primary
      epithelial cells to confluent monolayers in a standardized, high-yield and cost
      effective manner.

PMID- 28751426
TI  - PARP2 deficiency affects invariant-NKT-cell maturation and protects mice from
      concanavalin A-induced liver injury.
AB  - Excessive or persistent inflammation and hepatocyte death are the key triggers of
      liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death
      and inflammation. Chemical inhibition of PARP activity protects against liver
      injury during concanavalin A (ConA)-induced hepatitis. In this mice model, ConA
      activates immune cells, which promote inflammation and induce hepatocyte death,
      mediated by the activated invariant natural killer T (iNKT) lymphocyte
      population. We analyzed immune cell populations in the liver and several lymphoid
      organs, such as the spleen, thymus, and bone marrow in Parp2-deficient mice to
      better define the role of PARP proteins in liver immunity and inflammation at
      steady state and during ConA-induced hepatitis. We show that 1) the genetic
      inactivation of Parp2, but not Parp1, protected mice from ConA hepatitis without
      deregulating cytokine expression and leucocyte recruitment; 2) cellularity was
      lower in the thymus, but not in spleen, liver, or bone marrow of Parp2-/- mice;
      3) spleen and liver iNKT lymphocytes, as well as thymic T and NKT lymphocytes
      were reduced in Parp2 knockout mice. In conclusion, our results suggest that the
      defect of T-lymphocyte maturation in Parp2 knockout mice leads to a systemic
      reduction of iNKT cells, reducing hepatocyte death during ConA-mediated liver
      damage, thus protecting the mice from hepatitis.NEW & NOTEWORTHY The genetic
      inactivation of Parp2, but not Parp1, protects mice from concanavalin A
      hepatitis. Immune cell populations are lower in the thymus, but not in the
      spleen, liver, or bone marrow of Parp2-deficient mice compared with wild-type
      mice. Spleen and liver invariant natural killer T (NKT) lymphocytes, as well as
      thymic T and NKT lymphocytes, are reduced in Parp2-deficient mice.

PMID- 28751425
TI  - Melatonin inhibits hypothalamic gonadotropin-releasing hormone release and
      reduces biliary hyperplasia and fibrosis in cholestatic rats.
AB  - Melatonin is a hormone produced by the pineal gland with increased circulating
      levels shown to inhibit biliary hyperplasia and fibrosis during cholestatic liver
      injury. Melatonin also has the capability to suppress the release of hypothalamic
      gonadotropin-releasing hormone (GnRH), a hormone that promotes cholangiocyte
      proliferation when serum levels are elevated. However, the interplay and
      contribution of neural melatonin and GnRH to cholangiocyte proliferation and
      fibrosis in bile duct-ligated (BDL) rats have not been investigated. To test
      this, cranial levels of melatonin were increased by implanting osmotic minipumps
      that performed an intracerebroventricular (ICV) infusion of melatonin or saline
      for 7 days starting at the time of BDL. Hypothalamic GnRH mRNA and cholangiocyte
      secretion of GnRH and melatonin were assessed. Cholangiocyte proliferation and
      fibrosis were measured. Primary human hepatic stellate cells (HSCs) were treated
      with cholangiocyte supernatants, GnRH, or the GnRH receptor antagonist cetrorelix
      acetate, and cell proliferation and fibrosis gene expression were assessed.
      Melatonin infusion reduced hypothalamic GnRH mRNA expression and led to decreased
      GnRH and increased melatonin secretion from cholangiocytes. Infusion of melatonin
      was found to reduce hepatic injury, cholangiocyte proliferation, and fibrosis
      during BDL-induced liver injury. HSCs supplemented with BDL cholangiocyte
      supernatant had increased proliferation, and this increase was reversed when HSCs
      were supplemented with supernatants from melatonin-infused rats. GnRH stimulated
      fibrosis gene expression in HSCs, and this was reversed by cetrorelix acetate
      cotreatment. Increasing bioavailability of melatonin in the brain may improve
      outcomes during cholestatic liver disease.NEW & NOTEWORTHY We have previously
      demonstrated that GnRH is expressed in cholangiocytes and promotes their
      proliferation during cholestasis. In addition, dark therapy, which increases
      melatonin, reduced cholangiocyte proliferation and fibrosis during cholestasis.
      This study expands these findings by investigating neural GnRH regulation by
      melatonin during BDL-induced cholestasis by infusing melatonin into the brain.
      Melatonin infusion reduced cholangiocyte proliferation and fibrosis, and these
      effects are due to GNRH receptor 1-dependent paracrine signaling between
      cholangiocytes and hepatic stellate cells.

PMID- 28751427
TI  - Unremitting watery diarrhoea in early childhood period.
AB  - Chronic watery diarrhoea can be a presentation of gastrointestinal disease itself
      or a less-evident systemic disease. A 17-month-old boy presented with intractable
      diarrhoea, failure to gain weight, refractory tachycardia and severe
      hypertension. The ability to recognise and make a quick diagnosis of secretory
      type of diarrhoea dictated the outcome of patients with this ailment.
      Catecholamine hypersecretion was considered with the additional clues of
      refractory tachycardia and hypertension, a well-recognised phenomenon of
      neuroblastic tumours. A neuroblastic tumour can lead to vasoactive intestinal
      peptide (VIP) overexpression, which may result in secretory diarrhoea. In this
      situation, measurements of plasma VIP enabled crucial diagnosis. Imaging studies
      were used to identify and localise a neuroblastic tumour. Subsequent removal of
      the tumour was curative and led to the resolution of the symptoms.

PMID- 28751428
TI  - Cerebral haemorrhage as a clinical manifestation of human ehrlichiosis.
AB  - A 16-year-old young man presented to the emergency room with new-onset
      generalised tonic-clonic seizures. Examination showed a Glasgow score of 13 and
      predominantly crural left hemiparesis. Imaging demonstrated a right
      frontoparietal haemorrhage of non-vascular origin with perilesional oedema.
      Surgical drainage was carried out, but rebleeding occurred within 24 hours
      following surgery, and again 1 week after discharge. On reinterrogation and
      examination, Ehrlichia canis infection was suspected and empirical management
      with doxycycline was begun. Improvement was evident 72 hours after antibiotic
      initiation, and PCR confirmed the diagnosis; thus, doxycycline was continued for
      6 months. After 2 years, seizures recurred and treatment was reinstated with good
      clinical response. However, seizures reappeared whenever treatment
      discontinuation was attempted. Lacking alternatives, doxycycline was maintained
      up to the third year following the initial episode. Subsequently, the patient
      showed complete resolution without neurological sequelae up to his last follow-up
      visit, 12 months following treatment cessation.

PMID- 28751429
TI  - Energy drinks give you wings but also an abnormal exercise test.
AB  - This is the case of a 53-year-old man with known coronary artery disease who
      underwent two exercise treadmill tests (ETT). The first test, which yielded an
      abnormal result, was undertaken shortly after he had drunk two cans of Red Bull,
      a popular energy drink (ED). A second ETT was undertaken 1 week later by the same
      team without EDs on board and the test result was normal. This case suggests that
      drinking EDs prior to an ETT could lead to a false positive result and should be
      discouraged prior to exercise testing.

PMID- 28751430
TI  - Persistent air leak after pulmonary transplantation.
AB  - A 59-year-old man with bilateral apical emphysema underwent a double lung
      transplant for end-stagechronic obstructive pulmonary disease leaving remnant
      right apical native tissue due to pleural adhesions. Initial postoperative course
      was uneventful until the chest drains were removed. This revealed a small
      pneumomediastinum, which progressively increased in size causing gross surgical
      emphysema. Re-insertion of the chest drain stabilised the patient so that the
      cause could be identified and corrected. Two bronchoscopies excluded anastomotic
      dehiscence as a cause. Therefore the subcostal wound was refashioned under video
      assisted thoracoscopic surgery in case there was a defect. Unfortunately this
      also failed to halt the air leak; therefore another cause was sought. A
      multidisciplinary team meeting review of the radiology revealed that the
      patient's native bullous tissue was still inflated. Subsequent bronchoscopy
      revealed a native bronchial communication, due to variant anatomy, proximal to
      the surgical anastomosis. This was subsequently occluded using a bronchial valve
      allowing the patient to make a swift recovery.

PMID- 28751431
TI  - A rare case of persistent nephropleural fistula following percutaneous
      nephrolithotomy.
AB  - Nephropleural fistula following percutaneous nephrolithotomy (PCNL) is a very
      rare complication and there are only a few case reports available in the
      literature. We present a case of a 65-year-old male patient with a right staghorn
      renal calculus and a left upper ureteric calculus who developed a right
      nephropleural fistula following right-sided PCNL. The patient required
      intercostal tube drainage. The cause of the fistula was identified to be a
      superior calyceal infundibular obstruction due to tiny residual stone fragments
      and oedema, which was endoscopically dilated, and the fistula subsequently
      healed. Urinary diversion using chest drainage and percutaneous nephrostomy
      followed by infundibular dilation and removal of secondary stones allowed the
      successful closure of the nephropleural fistula in our case.

PMID- 28751432
TI  - Severe hypokalaemia as a cause of acute transient quadriparesis.
AB  - Hypokalaemic paralysis covers a heterogeneous group of disorders caused either by
      an enhanced shift of potassium into the cells or following a significant renal or
      gastrointestinal loss of potassium. We present the case of a 48-year-old
      Caucasian man with paralysis of both upper and lower extremities. ECG showed
      sinus rhythm and characteristic changes of hypokalaemia with depression of the ST
      segment, prolonged QTc interval of 581ms and U waves seen as a small positive
      deflection at the T wave in the middle precordial leads. We suspected the cause
      of hypokalaemia leading to paralysis to be due to administration of high doses of
      furosemide without oral potassium supplementation coupled with regular use of
      insulin. Initial therapy included both oral and intravenous potassium replacement
      and close monitoring of cardiac rhythm and serum potassium levels. Twenty-four
      hours after admission, the potassium level had normalised and the patient slowly
      recovered and gained strength. The patient was discharged after 1 week of careful
      follow-up and did not experience any serious degree of rebound hyperkalaemia. At
      the time of discharge, all laboratory tests were normal and ECG revealed a normal
      sinus rhythm and normal QTc intervals.

PMID- 28751433
TI  - Ecthyma gangrenosum caused by Citrobacter freundii.
AB  - A 55-year-old man undergoing chemotherapy for recurrent multiple myeloma
      presented with a 2-day history of bilateral lower leg rash with pain and oedema.
      On examination, there were numerous non-palpable retiform pruritic patches over
      both lower legs. Skin pnch biopsy demonstrated a diffuse interstitial
      neutrophilic infiltrate with necrosis. Peripheral blood and skin tissue cultures
      both isolated Citrobacterfreundii, consistent with a rare form of ecthyma
      gangrenosum. The patient responded with appropriate antibiotic therapy and
      removal of medical port. He made a full recovery from this infectious
      complication of his underlying immunosuppression.

PMID- 28751434
TI  - Atypical presentation and management of fibrodysplasia ossificans progressiva.
AB  - We report a case of an 18-year-old woman, with bilateral acute inflammatory pain
      on the hip area, during the premenstrual period, and progressive increase in
      volume and rigidity of both hips. Bilateral exuberant soft tissue calcifications
      were present on the radiographic exams, and the patient also presented with
      bilateral short-length hallux valgus. A heterozygous mutation in the protein
      kinase domain of ACVR1 gene was found, allowing the diagnosis of fibrodysplasia
      ossificans progressive. Due to the relation between the disease flares and the
      premenstrual period, the patient was put into a chemically induced amenorrhea,
      with no new inflammatory crises since.This case illustrates the importance of an
      accurate diagnosis to prevent unnecessary diagnostic procedures, as well as the
      need to develop specific treatment strategies to address each patient's
      particular needs.

PMID- 28751435
TI  - Thompson's hip hemiarthroplasty for neck of femur fracture: remarkable clinical
      outcomes at 45-year follow-up.

PMID- 28751436
TI  - A striking image of spontaneous echo contrast in severe mitral stenosis in a
      patient with good international normalised ratio (INR) control.

PMID- 28751437
TI  - Enhanced recovery after surgery for hip and knee arthroplasty: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: To collect data of randomised controlled trials (RCTs) and clinical
      controlled trials (CCTs) for evaluating the effects of enhanced recovery after
      surgery on postoperative recovery of patients who received total hip arthroplasty
      (THA) or total knee arthroplasty (TKA). METHODS: Relevant, published studies were
      identified using the following key words: arthroplasty, joint replacement,
      enhanced recovery after surgery, fast track surgery, multi-mode analgesia, diet
      management, or steroid hormones. The following databases were used to identify
      the literature consisting of RCTs or CCTs with a date of search of 31 December
      2016: PubMed, Cochrane, Web of knowledge, Ovid SpringerLink and EMBASE. All
      relevant data were collected from studies meeting the inclusion criteria. The
      outcome variables were postoperative length of stay (LOS), 30-day readmission
      rate, and total incidence of complications. RevMan5.2. software was adopted for
      the meta-analysis. RESULTS: A total of 10 published studies (9936 cases) met the
      inclusion criteria. The cumulative data included 4205 cases receiving enhanced
      recovery after surgery (ERAS), and 5731 cases receiving traditional recovery
      after surgery (non-ERAS). The meta-analysis showed that LOS was significantly
      lower in the ERAS group than in the control group (non-ERAS group) (p<0.01), and
      there were fewer incidences of complications in the ERAS group than in the
      control group (p=0.03). However, no significant difference was found in the 30
      day readmission rate (p=0.18). CONCLUSIONS: ERAS significantly reduces LOS and
      incidence of complications in patients who have had THA or TKA. However, ERAS
      does not appear to significantly impact 30-day readmission rates.

PMID- 28751438
TI  - Physical activity patterns and socio-demographic correlates of physical activity
      among medical undergraduates in Sri Lanka: an observational study.
AB  - BACKGROUND: Physical inactivity is the fourth leading risk factor for mortality
      worldwide and a leading risk factor for type 2 diabetes and cardiovascular
      disease. Medical undergraduates are a group of young adults expected to have a
      sound knowledge of the benefits of physical activity (PA) and have an active
      lifestyle. OBJECTIVE: To quantifyPA levels among medical undergraduates of a Sri
      Lankan university and to determine the socio-demographic correlates of physical
      inactivity. METHODS: Medical undergraduates in their third, fourth and fifth
      years of study were recruited for this quantitative, descriptive, cross-sectional
      study using a self-administered questionnaire. RESULTS: A total of 421 students
      were recruited. Overall 41% were physically inactive. Females (47%) were more
      inactive than males (34%). The total mean weekly metabolic equivalent (MET)
      minutes was 1468.2+/-1873. Males (1676.2+/-1629) had a higher mean weekly MET
      minutes than females (1319+/-20102), p=0.05. 88% owned a portable internet device
      such as a smartphone or tablet. Students using health-related apps on their
      devices had significantly higherPA (p=0.01) and lower body mass index (BMI)
      (p=0.04), than those who did not. Binary logistic regression revealed physical
      inactivity to be significantly associated with gender (p=0.01), not using a
      health-promoting app on their portable device (p=0.01) and the year of study
      (p=0.03). CONCLUSION: Physical inactivity is a significant problem among medical
      undergraduates. The use of health applications was associated with a higher PA
      and lower BMI. The reasons for inactivity and the discrepancy in activity levels
      between males and females needs to be explored in greater detail.

PMID- 28751439
TI  - Recent advances in the treatment of erectile dysfunction.
AB  - Erectile dysfunction (ED) is one of the most common conditions affecting middle
      aged and older men. Nearly every primary care physician, internist and
      geriatrician will be called upon to manage this condition or to make referrals to
      urologists, endocrinologists and cardiologists who will assist in the treatment
      of ED. This article will briefly discuss the diagnosis and management of ED. In
      addition, emerging concepts in ED management will be discussed, such as the use
      of testosterone to treat ED, the role of the endothelium in men with ED and
      treating the partner of the man with ED. Finally, future potential therapies for
      ED will be discussed.

PMID- 28751440
TI  - Exposure-Response of Veliparib to Inform Phase II Trial Design in Refractory or
      Relapsed Patients with Hematological Malignancies.
AB  - Purpose: A phase I trial of veliparib in combination with topotecan plus
      carboplatin (T+C) demonstrated a 33% objective response rate in patients with
      hematological malignancies. The objective is to perform exposure-response
      analysis to inform the phase II trial design.Experimental Design:
      Pharmacokinetic, efficacy, and safety data from 95 patients, who were
      administered 10 to 100 mg b.i.d. doses of veliparib for either 8, 14, or 21 days
      with T+C, were utilized for exposure-efficacy (objective response and overall
      survival) and exposure-safety (>=grade 3 mucositis) analysis. Multivariate cox
      proportional hazards and logistic regression analyses were conducted. The
      covariates evaluated were disease status, duration of treatment, and number of
      prior therapies.Results: The odds of having objective response were 1.08-fold
      with 1,000 ng/hr/mL increase in AUC, 1.8-fold with >8 days treatment, 2.8-fold in
      patients with myeloproliferative neoplasms (MPN), and 0.5-fold with >=2 prior
      therapies. Based on analysis of overall survival, hazard of death decreased by
      1.5% for 1,000 ng/hr/mL increase in AUC, 39% with >8 days treatment, 44% in
      patients with MPN, while increased by 19% with >=2 prior therapies. The odds of
      having >=grade 3 mucositis increased by 29% with 1,000 ng.h/mL increase in
      AUC.Conclusions: Despite shallow exposure-efficacy relationship, doses lower than
      80 mg do not exceed veliparib single agent preclinical IC50 Shallow exposure
      mucositis relationship also supports the 80-mg dose. Based on benefit/risk
      assessment, veliparib at a dose of 80 mg b.i.d. for at least 14 days in
      combination with T+C is recommended to be studied in MPN patients. Clin Cancer
      Res; 23(21); 6421-9. (c)2017 AACR.

PMID- 28751441
TI  - miRomics and Proteomics Reveal a miR-296-3p/PRKCA/FAK/Ras/c-Myc Feedback Loop
      Modulated by HDGF/DDX5/beta-catenin Complex in Lung Adenocarcinoma.
AB  - Purpose: This study was performed to identify the detailed mechanisms by which
      miR-296-3p functions as a tumor suppressor to prevent lung adenocarcinoma (LADC)
      cell growth, metastasis, and chemoresistance.Experimental Design: The miR-296-3p
      expression was examined by real-time PCR and in situ hybridization. MTT, EdU
      incorporation, Transwell assays, and MTT cytotoxicity were respectively performed
      for cell proliferation, metastasis, and chemoresistance; Western blotting was
      performed to analyze the pathways by miR-296-3p and HDGF/DDX5 complex. The miRNA
      microarray and luciferase reporter assays were respectively used for the HDGF
      mediated miRNAs and target genes of miR-296-3p. The ChIP, EMSA assays, and
      coimmunoprecipitation combined with mass spectrometry and GST pull-down were
      respectively designed to analyze the DNA-protein complex and HDGF/DDX5/beta
      catenin complex.Results: We observed that miR-296-3p not only controls cell
      proliferation and metastasis, but also sensitizes LADC cells to cisplatin (DDP)
      in vitro and in vivo Mechanistic studies demonstrated that miR-296-3p directly
      targets PRKCA to suppress FAK-Ras-c-Myc signaling, thus stimulating its own
      expression in a feedback loop that blocks cell cycle and epithelial-mesenchymal
      transition (EMT) signal. Furthermore, we observed that suppression of HDGF-beta
      catenin-c-Myc signaling activates miR-296-3p, ultimately inhibiting the PRKCA-FAK
      Ras pathway. Finally, we found that DDX5 directly interacts with HDGF and induces
      beta-catenin-c-Myc, which suppresses miR-296-3p and further activates PRKCA-FAK
      Ras, cell cycle, and EMT signaling. In clinical samples, reduced miR-296-3p is an
      unfavorable factor that inversely correlates with HDGF/DDX5, but not
      PRKCA.Conclusions: Our study provides a novel mechanism that the miR-296-3p-PRKCA
      FAK-Ras-c-Myc feedback loop modulated by HDGF/DDX5/beta-catenin complex
      attenuates cell growth, metastasis, and chemoresistance in LADC. Clin Cancer Res;
      23(20); 6336-50. (c)2017 AACR.

PMID- 28751442
TI  - Toward Precision Radiotherapy for Use with Immune Checkpoint Blockers.
AB  - The first evidence that radiotherapy enhances the efficacy of immune checkpoint
      blockers (ICB) was obtained a dozen years ago in a mouse model of metastatic
      carcinoma refractory to anti-CTLA-4 treatment. At the time, ICBs had just entered
      clinical testing, an endeavor that culminated in 2011 with the approval of the
      first anti-CTLA-4 antibody for use in metastatic melanoma patients (ipilimumab).
      Thereafter, some patients progressing on ipilimumab showed systemic responses
      only upon receiving radiation to one lesion, confirming clinically the
      proimmunogenic effects of radiation. Preclinical data demonstrate that multiple
      immunomodulators synergize with radiotherapy to cause the regression of
      irradiated tumors and, less often, nonirradiated metastases. However, the impact
      of dose and fractionation on the immunostimulatory potential of radiotherapy has
      not been thoroughly investigated. This issue is extremely relevant given the
      growing number of clinical trials testing the ability of radiotherapy to increase
      the efficacy of ICBs. Recent data demonstrate that the recruitment of dendritic
      cells to neoplastic lesions (and hence the priming of tumor-specific CD8+ T
      cells) is highly dependent on radiotherapy dose and fractionation through a
      mechanism that involves the accumulation of double-stranded DNA in the cytoplasm
      of cancer cells and consequent type I IFN release. The molecular links between
      the cellular response to radiotherapy and type I IFN secretion are just being
      uncovered. Here, we discuss the rationale for an optimized use of radiotherapy as
      well as candidate biomarkers that may predict clinical responses to radiotherapy
      combined with ICBs. Clin Cancer Res; 24(2); 259-65. (c)2017 AACR.

PMID- 28751443
TI  - FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious
      BRCA Mutation-Associated Advanced Ovarian Cancer.
AB  - On December 19, 2016, the FDA granted accelerated approval to rucaparib (RUBRACA;
      Clovis Oncology, Inc.) for the treatment of patients with deleterious BRCA
      mutation (germline and/or somatic)-associated advanced ovarian cancer who have
      been treated with two or more chemotherapies. The FDA also approved the
      FoundationFocus CDx BRCA test (Foundation Medicine, Inc.), the first next
      generation sequencing-based companion diagnostic, for identifying patients with
      advanced ovarian cancer eligible for treatment with rucaparib based on detection
      of deleterious BRCA1 and/or BRCA2 mutations in tumor tissue. Rucaparib's approval
      was based primarily on efficacy data from 106 patients with BRCA mutation
      associated ovarian cancer who had prior treatment with two or more chemotherapies
      and safety data from 377 patients with ovarian cancer treated with rucaparib 600
      mg orally twice daily on two open-label, single-arm trials. Investigator-assessed
      objective response rate was 54% [57/106; 95% confidence interval (CI), 44-64],
      and median duration of response was 9.2 months (95% CI, 6.6-11.7). The approved
      companion diagnostic verified tumor BRCA mutation status retrospectively in 96%
      (64/67) of patients. Common adverse reactions (>=20%) to rucaparib were nausea,
      fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased
      appetite, diarrhea, thrombocytopenia, and dyspnea. This article summarizes the
      FDA review and data supporting rucaparib's accelerated approval. Clin Cancer Res;
      23(23); 7165-70. (c)2017 AACRSee related commentary by Kohn et al., p. 7155.

PMID- 28751444
TI  - Pediatric Phase I Trial and Pharmacokinetic Study of Trebananib in Relapsed Solid
      Tumors, Including Primary Tumors of the Central Nervous System ADVL1115: A
      Children's Oncology Group Phase I Consortium Report.
AB  - Purpose: Trebananib is a first-in-class antiangiogenic peptibody (peptide-Fc
      fusion protein) that inhibits Angiopoietin 1 and 2. A pediatric phase 1 trial was
      performed to define trebananib dose-limiting toxicities (DLT), recommended phase
      2 dose (RP2D), and pharmacokinetics (PK).Experimental Design: Trebananib was
      administered by weekly infusion. Three dose levels (10, 15, or 30 mg/kg/dose)
      were evaluated using a rolling-six design. Part 2 evaluated a cohort of subjects
      with primary central nervous system (CNS) tumors. Pharmacokinetic sampling and
      analysis of peripheral blood biomarkers was performed during the first 4 weeks.
      Response was evaluated after 8 weeks. Correlative studies included angiogenic
      protein expression and DCE-MRI.Results: Thirty-seven subjects were enrolled (31
      evaluable for toxicity) with median age 12 years (range, 2 to 21). Two of 19
      evaluable non-CNS subjects developed DLT at the 30 mg/kg dose level, including
      venous thrombosis and pleural effusion. In the CNS cohort, 3/12 subjects
      developed DLT, including decreased platelet count, transient ischemic attack, and
      cerebral edema with headache and hydrocephalus. Other grade 3 or 4 toxicities
      included lymphopenia (n = 4), anemia, thrombocytopenia, neutropenia, vomiting,
      and hypertension (n = 1 each). Response included stable disease in 7 subjects, no
      partial or complete responses. Two subjects continued study treatment with
      prolonged stable disease for 18 cycles (neuroblastoma) and 26 cycles (anaplastic
      astrocytoma). Pharmacokinetics appeared linear over 3 dose levels. Correlative
      studies demonstrated increased PlGF and sVCAM-1, but no change in endoglin or
      perfusion by DCE-MRI.Conclusions: Trebananib was well tolerated in pediatric
      patients with recurrent or refractory solid or CNS tumors. RP2D is 30 mg/kg. Clin
      Cancer Res; 23(20); 6062-9. (c)2017 AACR.

PMID- 28751445
TI  - Head and Neck Carcinoma Immunotherapy: Facts and Hopes.
AB  - Cancer of the head and neck (HNC) is a heterogeneous disease of the upper
      aerodigestive tract, encompassing distinct histologic types, different anatomic
      sites, and human papillomavirus (HPV)-positive as well as HPV-negative cancers.
      Advanced/recurrent HNCs have poor prognosis with low survival rates. Tumor
      mediated inhibition of antitumor immune responses and a high mutational burden
      are common features of HNCs. Both are responsible for the successful escape of
      these tumors from the host immune system. HNCs evolve numerous mechanisms of
      evasion from immune destruction. These mechanisms are linked to genetic
      aberrations, so that HNCs with a high mutational load are also highly
      immunosuppressive. The tumor microenvironment of these cancers is populated by
      immune cells that are dysfunctional, inhibitory cytokines, and exosomes carrying
      suppressive ligands. Dysfunctional immune cells in patients with
      recurrent/metastatic HNC can be made effective by the delivery of immunotherapies
      in combination with conventional treatments. With many promising immune-based
      strategies available, the future of immune therapies in HNC is encouraging,
      especially as methods for genetic profiling and mapping the immune landscape of
      the tumor are being integrated into a personalized approach. Efficiency of immune
      therapies is expected to rapidly improve with the possibility for patients'
      selection based on personal immunogenomic profiles. Noninvasive biomarkers of
      response to therapy will be emerging as a better understanding of the various
      molecular signals co-opted by the tumors is gained. The emerging role of
      immunotherapy as a potentially beneficial addition to standard treatments for
      recurrent/metastatic HNC offers hope to the patients for whom no other
      therapeutic options exist. Clin Cancer Res; 24(1); 6-13. (c)2017 AACR.

PMID- 28751446
TI  - Gene Copy Number Estimation from Targeted Next-Generation Sequencing of Prostate
      Cancer Biopsies: Analytic Validation and Clinical Qualification.
AB  - Purpose: Precise detection of copy number aberrations (CNA) from tumor biopsies
      is critically important to the treatment of metastatic prostate cancer. The use
      of targeted panel next-generation sequencing (NGS) is inexpensive, high
      throughput, and easily feasible, allowing single-nucleotide variant calls, but
      CNA estimation from this remains challenging.Experimental Design: We evaluated
      CNVkit for CNA identification from amplicon-based targeted NGS in a cohort of 110
      fresh castration-resistant prostate cancer biopsies and used capture-based whole
      exome sequencing (WES), array comparative genomic hybridization (aCGH), and FISH
      to explore the viability of this approach.Results: We showed that this method
      produced highly reproducible CNA results (r = 0.92), with the use of pooled
      germline DNA as a coverage reference supporting precise CNA estimation. CNA
      estimates from targeted NGS were comparable with WES (r = 0.86) and aCGH (r =
      0.7); for key selected genes (BRCA2, MYC, PIK3CA, PTEN, and RB1), CNA estimation
      correlated well with WES (r = 0.91) and aCGH (r = 0.84) results. The frequency of
      CNAs in our population was comparable with that previously described (i.e., deep
      deletions: BRCA2 4.5%; RB1 8.2%; PTEN 15.5%; amplification: AR 45.5%; gain: MYC
      31.8%). We also showed, utilizing FISH, that CNA estimation can be impacted by
      intratumor heterogeneity and demonstrated that tumor microdissection allows NGS
      to provide more precise CNA estimates.Conclusions: Targeted NGS and CNVkit-based
      analyses provide a robust, precise, high-throughput, and cost-effective method
      for CNA estimation for the delivery of more precise patient care. Clin Cancer
      Res; 23(20); 6070-7. (c)2017 AACR.

PMID- 28751447
TI  - Numb-/low Enriches a Castration-Resistant Prostate Cancer Cell Subpopulation
      Associated with Enhanced Notch and Hedgehog Signaling.
AB  - Purpose: To elucidate the role and molecular mechanism of Numb in prostate cancer
      and the functional contribution of Numb-/low prostate cancer cells in castration
      resistance.Experimental Design: The expression of Numb was assessed using
      multiple Oncomine datasets and prostate cancer tissues from both humans and mice.
      The biological effects of the overexpression and knockdown of Numb in human
      prostate cancer cell lines were investigated in vitro and in vivo In addition, we
      developed a reliable approach to distinguish between prostate cancer cell
      populations with a high or low endogenous expression of Numb protein using a Numb
      promoter-based lentiviral reporter system. The difference between Numb-/low and
      Numbhigh prostate cancer cells in the response to androgen-deprivation therapy
      (ADT) was then tested. The likely downstream factors of Numb were analyzed using
      luciferase reporter assays, immunoblotting, and quantitative real-time
      PCR.Results: We show here that Numb was downregulated and negatively correlated
      with prostate cancer advancement. Functionally, Numb played an inhibitory role in
      xenograft prostate tumor growth and castration-resistant prostate cancer
      development by suppressing Notch and Hedgehog signaling. Using a Numb promoter
      based lentiviral reporter system, we were able to distinguish Numb-/low prostate
      cancer cells from Numbhigh cells. Numb-/low prostate cancer cells were smaller
      and quiescent, preferentially expressed Notch and Hedgehog downstream and stem
      cell-associated genes, and associated with a greater resistance to ADT. The
      inhibition of the Notch and Hedgehog signaling pathways significantly increased
      apoptosis in Numb-/low cells in response to ADT.Conclusions: Numb-/low enriches a
      castration-resistant prostate cancer cell subpopulation that is associated with
      unregulated Notch and Hedgehog signaling. Clin Cancer Res; 23(21); 6744-56.
      (c)2017 AACR.

PMID- 28751448
TI  - Association of FGFR1 with ERalpha Maintains Ligand-Independent ER Transcription
      and Mediates Resistance to Estrogen Deprivation in ER+ Breast Cancer.
AB  - Purpose:FGFR1 amplification occurs in approximately 15% of estrogen receptor
      positive (ER+) human breast cancers. We investigated mechanisms by which FGFR1
      amplification confers antiestrogen resistance to ER+ breast cancer.Experimental
      Design: ER+ tumors from patients treated with letrozole before surgery were
      subjected to Ki67 IHC, FGFR1 FISH, and RNA sequencing (RNA-seq). ER+/FGFR1
      amplified breast cancer cells, and patient-derived xenografts (PDX) were treated
      with FGFR1 siRNA or the FGFR tyrosine kinase inhibitor lucitanib. Endpoints were
      cell/xenograft growth, FGFR1/ERalpha association by coimmunoprecipitation and
      proximity ligation, ER genomic activity by ChIP sequencing, and gene expression
      by RT-PCR.Results: ER+/FGFR1-amplified tumors in patients treated with letrozole
      maintained cell proliferation (Ki67). Estrogen deprivation increased total and
      nuclear FGFR1 and FGF ligands expression in ER+/FGFR1-amplified primary tumors
      and breast cancer cells. In estrogen-free conditions, FGFR1 associated with
      ERalpha in tumor cell nuclei and regulated the transcription of ER-dependent
      genes. This association was inhibited by a kinase-dead FGFR1 mutant and by
      treatment with lucitanib. ChIP-seq analysis of estrogen-deprived ER+/FGFR1
      amplified cells showed binding of FGFR1 and ERalpha to DNA. Treatment with
      fulvestrant and/or lucitanib reduced FGFR1 and ERalpha binding to DNA. RNA-seq
      data from FGFR1-amplified patients' tumors treated with letrozole showed
      enrichment of estrogen response and E2F target genes. Finally, growth of
      ER+/FGFR1-amplified cells and PDXs was more potently inhibited by fulvestrant and
      lucitanib combined than each drug alone.Conclusions: These data suggest the
      ERalpha pathway remains active in estrogen-deprived ER+/FGFR1-amplified breast
      cancers. Therefore, these tumors are endocrine resistant and should be candidates
      for treatment with combinations of ER and FGFR antagonists. Clin Cancer Res;
      23(20); 6138-50. (c)2017 AACR.

PMID- 28751449
TI  - T2-FLAIR Mismatch, an Imaging Biomarker for IDH and 1p/19q Status in Lower-grade
      Gliomas: A TCGA/TCIA Project.
AB  - Purpose: Lower-grade gliomas (WHO grade II/III) have been classified into
      clinically relevant molecular subtypes based on IDH and 1p/19q mutation status.
      The purpose was to investigate whether T2/FLAIR MRI features could distinguish
      between lower-grade glioma molecular subtypes.Experimental Design: MRI scans from
      the TCGA/TCIA lower grade glioma database (n = 125) were evaluated by two
      independent neuroradiologists to assess (i) presence/absence of homogenous signal
      on T2WI; (ii) presence/absence of "T2-FLAIR mismatch" sign; (iii) sharp or
      indistinct lesion margins; and (iv) presence/absence of peritumoral edema.
      Metrics with moderate-substantial agreement underwent consensus review and were
      correlated with glioma molecular subtypes. Somatic mutation, DNA copy number, DNA
      methylation, gene expression, and protein array data from the TCGA lower-grade
      glioma database were analyzed for molecular-radiographic associations. A separate
      institutional cohort (n = 82) was analyzed to validate the T2-FLAIR mismatch
      sign.Results: Among TCGA/TCIA cases, interreader agreement was calculated for
      lesion homogeneity [kappa = 0.234 (0.111-0.358)], T2-FLAIR mismatch sign [kappa =
      0.728 (0.538-0.918)], lesion margins [kappa = 0.292 (0.135-0.449)], and
      peritumoral edema [kappa = 0.173 (0.096-0.250)]. All 15 cases that were positive
      for the T2-FLAIR mismatch sign were IDH-mutant, 1p/19q non-codeleted tumors (P <
      0.0001; PPV = 100%, NPV = 54%). Analysis of the validation cohort demonstrated
      substantial interreader agreement for the T2-FLAIR mismatch sign [kappa = 0.747
      (0.536-0.958)]; all 10 cases positive for the T2-FLAIR mismatch sign were IDH
      mutant, 1p/19q non-codeleted tumors (P < 0.00001; PPV = 100%, NPV =
      76%).Conclusions: Among lower-grade gliomas, T2-FLAIR mismatch sign represents a
      highly specific imaging biomarker for the IDH-mutant, 1p/19q non-codeleted
      molecular subtype. Clin Cancer Res; 23(20); 6078-85. (c)2017 AACR.

PMID- 28751450
TI  - Infiltrating T Cells Increase IDO1 Expression in Glioblastoma and Contribute to
      Decreased Patient Survival.
AB  - Purpose: Indoleamine 2,3 dioxygenase 1 (IDO1) mediates potent immunosuppression
      in multiple preclinical models of cancer. However, the basis for elevated IDO1
      expression in human cancer, including the most common primary malignant brain
      tumor in adults, glioblastoma (GBM), is poorly understood. The major objective of
      this study is to address this gap in our understanding of how IDO1 expression
      contributes to the biology of GBM, and whether its level of expression is a
      determinant of GBM patient outcome.Experimental Design: Patient-resected GBM, The
      Cancer Genome Atlas, human T-cell:GBM cocultures, as well as nu/nu, NOD-scid, and
      humanized (NSG-SGM3-BLT) mice-engrafted human GBM form the basis of our
      investigation.Results:In situ hybridization for IDO1 revealed transcript
      expression throughout patient-resected GBM, whereas immunohistochemical IDO1
      positivity was highly variable. Multivariate statistical analysis revealed that
      higher levels of IDO1 transcript predict a poor patient prognosis (P = 0.0076).
      GBM IDO1 mRNA levels positively correlated with increased gene expression for
      markers of cytolytic and regulatory T cells, in addition to decreased patient
      survival. Humanized mice intracranially engrafted human GBM revealed an IFNgamma
      associated T-cell-mediated increase of intratumoral IDO1Conclusions: Our data
      demonstrate that high intratumoral IDO1 mRNA levels correlate with a poor GBM
      patient prognosis. It also confirms the positive correlation between increased
      GBM IDO1 levels and human-infiltrating T cells. Collectively, this study suggests
      that future efforts aimed at increasing T-cell-mediated effects against GBM
      should consider combinatorial approaches that coinhibit potential T-cell-mediated
      IDO1 enhancement during therapy. Clin Cancer Res; 23(21); 6650-60. (c)2017 AACR.

PMID- 28751451
TI  - 131I-labeled Anti-HER2 Camelid sdAb as a Theranostic Tool in Cancer Treatment.
AB  - Purpose: Camelid single-domain antibody-fragments (sdAb) have beneficial
      pharmacokinetic properties, and those targeted to HER2 can be used for imaging of
      HER2-overexpressing cancer. Labeled with a therapeutic radionuclide, they may be
      used for HER2-targeted therapy. Here, we describe the generation of a 131I
      labeled sdAb as a theranostic drug to treat HER2-overexpressing
      cancer.Experimental Design: Anti-HER2 sdAb 2Rs15d was labeled with 131I using
      [131I]SGMIB and evaluated in vitro Biodistribution was evaluated in two HER2+
      murine xenograft models by micro-SPECT/CT imaging and at necropsy, and under
      challenge with trastuzumab and pertuzumab. The therapeutic potential of
      [131I]SGMIB-2Rs15d was investigated in two HER2+ tumor mouse models. A single
      dose toxicity study was performed in mice using unlabeled [127I]SGMIB-sdAb at 1.4
      mg/kg. The structure of the 2Rs15d-HER2 complex was determined by X-ray
      crystallography.Results: [131I]SGMIB-2Rs15d bound specifically to HER2+ cells (Kd
      = 4.74 +/- 0.39 nmol/L). High and specific tumor uptake was observed in both
      BT474/M1 and SKOV-3 tumor xenografted mice and surpassed kidney levels by 3
      hours. Extremely low uptake values were observed in other normal tissues at all
      time points. The crystal structure revealed that 2Rs15d recognizes HER2 Domain 1,
      consistent with the lack of competition with trastuzumab and pertuzumab observed
      in vivo [131I]SGMIB-2Rs15d alone, or in combination with trastuzumab, extended
      median survival significantly. No toxicity was observed after injecting
      [127I]SGMIB-2Rs15d.Conclusions: These findings demonstrate the theranostic
      potential of [131I]SGMIB-2Rs15d. An initial scan using low radioactive [*I]SGMIB
      2Rs15d allows patient selection and dosimetry calculations for subsequent
      therapeutic [131I]SGMIB-2Rs15d and could thereby impact therapy outcome on HER2+
      breast cancer patients. Clin Cancer Res; 23(21); 6616-28. (c)2017 AACR.

PMID- 28751452
TI  - Classic Spotlight, 1998 and 1999: Articles of Significant Interest Selected from
      the Journal of Virology Archives by the Editors.

PMID- 28751454
TI  - Cysteamine prevents vascular leakage through inhibiting transglutaminase in
      diabetic retina.
AB  - Cysteamine (an aminothiol), which is derived from coenzyme A degradation and
      metabolized into taurine, has beneficial effects against cystinosis and
      neurodegenerative diseases; however, its role in diabetic complications is
      unknown. Thus, we sought to determine the preventive effect of cysteamine against
      hyperglycemia-induced vascular leakage in the retinas of diabetic mice.
      Cysteamine and ethanolamine, the sulfhydryl group-free cysteamine analogue,
      inhibited vascular endothelial growth factor (VEGF)-induced stress fiber
      formation and vascular endothelial (VE)-cadherin disruption in endothelial cells,
      which play a critical role in modulating endothelial permeability. Intravitreal
      injection of the amine compounds prevented hyperglycemia-induced vascular leakage
      in the retinas of streptozotocin-induced diabetic mice. We then investigated the
      potential roles of reactive oxygen species (ROS) and transglutaminase (TGase) in
      the cysteamine prevention of VEGF-induced vascular leakage. Cysteamine, but not
      ethanolamine, inhibited VEGF-induced ROS generation in endothelial cells and
      diabetic retinas. In contrast, VEGF-induced TGase activation was prevented by
      both cysteamine and ethanolamine. Our findings suggest that cysteamine protects
      against vascular leakage through inhibiting VEGF-induced TGase activation rather
      than ROS generation in diabetic retinas.

PMID- 28751453
TI  - Maternal modifiers of the infant gut microbiota: metabolic consequences.
AB  - Transmission of metabolic diseases from mother to child is multifactorial and
      includes genetic, epigenetic and environmental influences. Evidence in rodents,
      humans and non-human primates support the scientific premise that exposure to
      maternal obesity or high-fat diet during pregnancy creates a long-lasting
      metabolic signature on the infant innate immune system and the juvenile
      microbiota, which predisposes the offspring to obesity and metabolic diseases. In
      neonates, gastrointestinal microbes introduced through the mother are noted for
      their ability to serve as direct inducers/regulators of the infant immune system.
      Neonates have a limited capacity to initiate an immune response. Thus, disruption
      of microbial colonization during the early neonatal period results in disrupted
      postnatal immune responses that highlight the neonatal period as a critical
      developmental window. Although the mechanisms are poorly understood, increasing
      evidence suggests that maternal obesity or poor diet influences the development
      and modulation of the infant liver and other end organs through direct
      communication via the portal system, metabolite production, alterations in gut
      barrier integrity and the hematopoietic immune cell axis. This review will focus
      on how maternal obesity and dietary intake influence the composition of the
      infant gut microbiota and how an imbalance or maladaptation in the microbiota,
      including changes in early pioneering microbes, might contribute to the
      programming of offspring metabolism with special emphasis on mechanisms that
      promote chronic inflammation in the liver. Comprehension of these pathways and
      mechanisms will elucidate our understanding of developmental programming and may
      expand the avenue of opportunities for novel therapeutics.

PMID- 28751455
TI  - Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K+ Channel
      Dysfunction in DRG Neurons.
AB  - Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root
      ganglion (DRG) neurons contributes to the hyperexcitability associated with
      persistent pain induced by spinal cord injury (SCI). However, the underlying
      mechanism is not known. In light of our previous work demonstrating modulation of
      the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase
      calcineurin (CaN) using electrophysiological, molecular, and imaging approaches
      in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small
      diameter DRG neurons slowed repolarization of the somatic action potential (AP)
      and attenuated the Kv3.4 current. Attenuated Kv3.4 currents also exhibited slowed
      inactivation. We observed similar effects on the recombinant Kv3.4 channel
      heterologously expressed in Chinese hamster ovary cells, supporting our findings
      in DRG neurons. Elucidating the molecular basis of these effects, mutation of
      four previously characterized serines within the Kv3.4 N-terminal inactivation
      domain eliminated the effects of CaN inhibition on the Kv3.4 current. SCI
      similarly induced concurrent Kv3.4 current attenuation and slowing of
      inactivation. Although there was little change in CaN expression and localization
      after injury, SCI induced upregulation of the native regulator of CaN 1 (RCAN1)
      in the DRG at the transcript and protein levels. Consistent with CaN inhibition
      resulting from RCAN1 upregulation, overexpression of RCAN1 in naive DRG neurons
      recapitulated the effects of pharmacological CaN inhibition on the Kv3.4 current
      and the AP. Overall, these results demonstrate a novel regulatory pathway that
      links CaN, RCAN1, and Kv3.4 in DRG neurons. Dysregulation of this pathway might
      underlie a peripheral mechanism of pain sensitization induced by SCI.SIGNIFICANCE
      STATEMENT Pain sensitization associated with spinal cord injury (SCI) involves
      poorly understood maladaptive modulation of neuronal excitability. Although
      central mechanisms have received significant attention, recent studies have
      identified peripheral nerve hyperexcitability as a driver of persistent pain
      signaling after SCI. However, the ion channels and signaling molecules
      responsible for this change in primary sensory neuron excitability are still not
      well defined. To address this problem, this study used complementary
      electrophysiological and molecular methods to determine how Kv3.4, a voltage
      gated K+ channel robustly expressed in dorsal root ganglion neurons, becomes
      dysfunctional upon calcineurin (CaN) inhibition. The results strongly suggest
      that CaN inhibition underlies SCI-induced dysfunction of Kv3.4 and the associated
      excitability changes through upregulation of the native regulator of CaN 1
      (RCAN1).

PMID- 28751456
TI  - Intermittent Hypoxia Enhances Functional Connectivity of Midcervical Spinal
      Interneurons.
AB  - Brief, intermittent oxygen reductions [acute intermittent hypoxia (AIH)] evokes
      spinal plasticity. Models of AIH-induced neuroplasticity have focused on
      motoneurons; however, most midcervical interneurons (C-INs) also respond to
      hypoxia. We hypothesized that AIH would alter the functional connectivity between
      C-INs and induce persistent changes in discharge. Bilateral phrenic nerve
      activity was recorded in anesthetized and ventilated adult male rats and a
      multielectrode array was used to record C4/5 spinal discharge before [baseline
      (BL)], during, and 15 min after three 5 min hypoxic episodes (11% O2, H1-H3).
      Most C-INs (94%) responded to hypoxia by either increasing or decreasing firing
      rate. Functional connectivity was examined by cross-correlating C-IN discharge.
      Correlograms with a peak or trough were taken as evidence for excitatory or
      inhibitory connectivity between C-IN pairs. A subset of C-IN pairs had increased
      excitatory cross-correlations during hypoxic episodes (34%) compared with BL
      (19%; p < 0.0001). Another subset had a similar response following each episode
      (40%) compared with BL (19%; p < 0.0001). In the latter group, connectivity
      remained elevated 15 min post-AIH (30%; p = 0.0002). Inhibitory C-IN connectivity
      increased during H1-H3 (4.5%; p = 0.0160), but was reduced 15 min post-AIH (0.5%;
      p = 0.0439). Spike-triggered averaging indicated that a subset of C-INs is
      synaptically coupled to phrenic motoneurons and excitatory inputs to these "pre
      phrenic" cells increased during AIH. We conclude that AIH alters connectivity of
      the midcervical spinal network. To our knowledge, this is the first demonstration
      that AIH induces plasticity within the propriospinal network.SIGNIFICANCE
      STATEMENT Acute intermittent hypoxia (AIH) can trigger spinal plasticity
      associated with sustained increases in respiratory, somatic, and/or autonomic
      motor output. The impact of AIH on cervical spinal interneuron (C-IN) discharge
      and connectivity is unknown. Our results demonstrate that AIH recruits excitatory
      C-INs into the spinal respiratory (phrenic) network. AIH also enhances excitatory
      and reduces inhibitory connections among the C-IN network. We conclude that C-INs
      are part of the respiratory, somatic, and/or autonomic response to AIH, and that
      propriospinal plasticity may contribute to sustained increases in motor output
      after AIH.

PMID- 28751457
TI  - 2-Arachidonoylglycerol Reduces Proteoglycans and Enhances Remyelination in a
      Progressive Model of Demyelination.
AB  - The failure to undergo remyelination is a critical impediment to recovery in
      multiple sclerosis. Chondroitin sulfate proteoglycans (CSPGs) accumulate at
      demyelinating lesions creating a nonpermissive environment that impairs axon
      regeneration and remyelination. Here, we reveal a new role for 2
      arachidonoylglycerol (2-AG), the major CNS endocannabinoid, in the modulation of
      CSPGs deposition in a progressive model of multiple sclerosis, the Theiler's
      murine encephalomyelitis virus-induced demyelinating disease. Treatment with a
      potent reversible inhibitor of the enzyme monoacylglycerol lipase, which accounts
      for 85% of the 2-AG degradation in the mouse CNS, modulates neuroinflammation and
      reduces CSPGs accumulation and astrogliosis around demyelinated lesions in the
      spinal cord of Theiler's murine encephalomyelitis virus-infected mice. Inhibition
      of 2-AG hydrolysis augments the number of mature oligodendrocytes and increases
      MBP, leading to remyelination and functional recovery of mice. Our findings
      establish a mechanism for 2-AG promotion of remyelination with implications in
      axonal repair in CNS demyelinating pathologies.SIGNIFICANCE STATEMENT The
      deposition of chondroitin sulfate proteoglycans contributes to the failure in
      remyelination associated with multiple sclerosis. Here we unveil a new role for 2
      arachidonoylglycerol, the major CNS endocannabinoid, in the modulation of
      chondroitin sulfate proteoglycan accumulation in Theiler's murine
      encephalomyelitis virus-induced demyelinating disease. The treatment during the
      chronic phase with a potent reversible inhibitor of the enzyme monoacylglycerol
      lipase, which accounts for 85% of the 2-arachidonoylglycerol degradation in the
      mouse CNS, modulates neuroinflammation and reduces chondroitin sulfate
      proteoglycan deposition around demyelinated lesions in the spinal cord of
      Theiler's murine encephalomyelitis virus-infected mice. The increased 2
      arachidonoylglycerol tone promotes remyelination in a model of progressive
      multiple sclerosis ameliorating motor dysfunction.

PMID- 28751458
TI  - Information-Theoretic Evidence for Predictive Coding in the Face-Processing
      System.
AB  - Predictive coding suggests that the brain infers the causes of its sensations by
      combining sensory evidence with internal predictions based on available prior
      knowledge. However, the neurophysiological correlates of (pre)activated prior
      knowledge serving these predictions are still unknown. Based on the idea that
      such preactivated prior knowledge must be maintained until needed, we measured
      the amount of maintained information in neural signals via the active information
      storage (AIS) measure. AIS was calculated on whole-brain beamformer-reconstructed
      source time courses from MEG recordings of 52 human subjects during the baseline
      of a Mooney face/house detection task. Preactivation of prior knowledge for faces
      showed as alpha-band-related and beta-band-related AIS increases in content
      specific areas; these AIS increases were behaviorally relevant in the brain's
      fusiform face area. Further, AIS allowed decoding of the cued category on a trial
      by-trial basis. Our results support accounts indicating that activated prior
      knowledge and the corresponding predictions are signaled in low-frequency
      activity (<30 Hz).SIGNIFICANCE STATEMENT Our perception is not only determined by
      the information our eyes/retina and other sensory organs receive from the outside
      world, but strongly depends also on information already present in our brains,
      such as prior knowledge about specific situations or objects. A currently popular
      theory in neuroscience, predictive coding theory, suggests that this prior
      knowledge is used by the brain to form internal predictions about upcoming
      sensory information. However, neurophysiological evidence for this hypothesis is
      rare, mostly because this kind of evidence requires strong a priori assumptions
      about the specific predictions the brain makes and the brain areas involved.
      Using a novel, assumption-free approach, we find that face-related prior
      knowledge and the derived predictions are represented in low-frequency brain
      activity.

PMID- 28751459
TI  - PTEN Loss Increases the Connectivity of Fast Synaptic Motifs and Functional
      Connectivity in a Developing Hippocampal Network.
AB  - Changes in synaptic strength and connectivity are thought to be a major mechanism
      through which many gene variants cause neurological disease. Hyperactivation of
      the PI3K-mTOR signaling network, via loss of function of repressors such as PTEN,
      causes epilepsy in humans and animal models, and altered mTOR signaling may
      contribute to a broad range of neurological diseases. Changes in synaptic
      transmission have been reported in animal models of PTEN loss; however, the full
      extent of these changes, and their effect on network function, is still unknown.
      To better understand the scope of these changes, we recorded from pairs of mouse
      hippocampal neurons cultured in a two-neuron microcircuit configuration that
      allowed us to characterize all four major connection types within the
      hippocampus. Loss of PTEN caused changes in excitatory and inhibitory
      connectivity, and these changes were postsynaptic, presynaptic, and transynaptic,
      suggesting that disruption of PTEN has the potential to affect most connection
      types in the hippocampal circuit. Given the complexity of the changes at the
      synaptic level, we measured changes in network behavior after deleting Pten from
      neurons in an organotypic hippocampal slice network. Slices containing Pten
      deleted neurons showed increased recruitment of neurons into network bursts.
      Importantly, these changes were not confined to Pten-deleted neurons, but
      involved the entire network, suggesting that the extensive changes in synaptic
      connectivity rewire the entire network in such a way that promotes a widespread
      increase in functional connectivity.SIGNIFICANCE STATEMENT Homozygous deletion of
      the Pten gene in neuronal subpopulations in the mouse serves as a valuable model
      of epilepsy caused by mTOR hyperactivation. To better understand how gene
      deletions lead to altered neuronal activity, we investigated the synaptic and
      network effects that occur 1 week after Pten deletion. PTEN loss increased the
      connectivity of all four types of hippocampal synaptic connections, including two
      forms of increased inhibition of inhibition, and increased network functional
      connectivity. These data suggest that single gene mutations that cause
      neurological diseases such as epilepsy may affect a surprising range of
      connection types. Moreover, given the robustness of homeostatic plasticity, these
      diverse effects on connection types may be necessary to cause network phenotypes
      such as increased synchrony.

PMID- 28751460
TI  - Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for
      Cocaine.
AB  - Addiction is often characterized by intense motivation for a drug, which may be
      narrowly focused at the expense of other rewards. Here, we examined the role of
      amygdala-related circuitry in the amplification and narrowing of motivation focus
      for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2)
      stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala
      (BLA) of female rats with one particular nose-poke porthole option for earning
      cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned
      identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly
      came to pursue their CeA ChR2-paired cocaine option intensely and exclusively,
      elevating cocaine intake while ignoring their alternative cocaine alone option.
      By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats
      also emitted consummatory bites toward their laser-paired porthole, suggesting
      that higher incentive salience made that cue more attractive. A separate
      progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified
      rats' motivation, raising their breakpoint effort price for cocaine by 10-fold.
      However, CeA ChR2 laser on its own lacked any reinforcement value: laser by
      itself was never self-stimulated, not even by the same rats in which it amplified
      motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen
      microinjections prevented acquisition of cocaine self-administration and laser
      preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed
      cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine
      motivation. We conclude that CeA ChR2 excitation paired with a cocaine option
      specifically focuses and amplifies motivation to produce intense pursuit and
      consumption focused on that single target.SIGNIFICANCE STATEMENT In addiction,
      intense incentive motivation often becomes narrowly focused on a particular drug
      of abuse. Here we show that pairing central nucleus of amygdala (CeA) optogenetic
      stimulation with one option for earning intravenous cocaine makes that option
      almost the exclusive focus of intense pursuit and consumption. CeA stimulation
      also elevated the effort cost rats were willing to pay for cocaine and made
      associated cues become intensely attractive. However, we also show that CeA laser
      had no reinforcing properties at all when given alone for the same rats.
      Therefore, CeA laser pairing makes its associated cocaine option and cues become
      powerfully attractive in a nearly addictive fashion.

PMID- 28751461
TI  - Novel Aberrations Uncovered in Barrett's Esophagus and Esophageal Adenocarcinoma
      Using Whole Transcriptome Sequencing.
AB  - Esophageal adenocarcinoma (EAC) has one of the fastest increases in incidence of
      any cancer, along with poor five-year survival rates. Barrett's esophagus (BE) is
      the main risk factor for EAC; however, the mechanisms driving EAC development
      remain poorly understood. Here, transcriptomic profiling was performed using RNA
      sequencing (RNA-seq) on premalignant and malignant Barrett's tissues to better
      understand this disease. Machine-learning and network analysis methods were
      applied to discover novel driver genes for EAC development. Identified gene
      expression signatures for the distinction of EAC from BE were validated in
      separate datasets. An extensive analysis of the noncoding RNA (ncRNA) landscape
      was performed to determine the involvement of novel transcriptomic elements in
      Barrett's disease and EAC. Finally, transcriptomic mutational investigation of
      genes that are recurrently mutated in EAC was performed. Through these
      approaches, novel driver genes were discovered for EAC, which involved key cell
      cycle and DNA repair genes, such as BRCA1 and PRKDC. A novel 4-gene signature
      (CTSL, COL17A1, KLF4, and E2F3) was identified, externally validated, and shown
      to provide excellent distinction of EAC from BE. Furthermore, expression changes
      were observed in 685 long noncoding RNAs (lncRNA) and a systematic dysregulation
      of repeat elements across different stages of Barrett's disease, with wide
      ranging downregulation of Alu elements in EAC. Mutational investigation revealed
      distinct pathways activated between EAC tissues with or without TP53 mutations
      compared with Barrett's disease. In summary, transcriptome sequencing revealed
      altered expression of numerous novel elements, processes, and networks in EAC and
      premalignant BE.Implications: This study identified opportunities to improve
      early detection and treatment of patients with BE and esophageal adenocarcinoma.
      Mol Cancer Res; 15(11); 1558-69. (c)2017 AACR.

PMID- 28751462
TI  - Selective MET Kinase Inhibition in MET-Dependent Glioma Models Alters Gene
      Expression and Induces Tumor Plasticity.
AB  - The receptor tyrosine kinase (RTK) MET represents a promising tumor target in a
      subset of glioblastomas. Most RTK inhibitors available in the clinic today,
      including those inhibiting MET, affect multiple targets simultaneously.
      Previously, it was demonstrated that treatment with cabozantinib (MET/VEGFR2/RET
      inhibitor) prolonged survival of mice carrying orthotopic patient-derived
      xenografts (PDX) of the MET-addicted glioblastoma model E98, yet did not prevent
      development of recurrent and cabozantinib-resistant tumors. To exclude VEGFR2
      inhibition-inflicted blood-brain barrier normalization and diminished tumor
      distribution of the drug, we have now investigated the effects of the novel MET
      selective inhibitor Compound A in the orthotopic E98 xenograft model. In vitro,
      Compound A proved a highly potent inhibitor of proliferation of MET-addicted cell
      lines. In line with its target selectivity, Compound A did not restore the leaky
      blood-brain barrier and was more effective than cabozantinib in inhibiting MET
      phosphorylation in vivo Compound A treatment significantly prolonged survival of
      mice carrying E98 tumor xenografts, but did not prevent eventual progression.
      Contrasting in vitro results, the Compound A-treated xenografts displayed high
      levels of AKT phosphorylation despite the absence of phosphorylated MET.
      Profiling by RNA sequencing showed that in vivo transcriptomes differed
      significantly from those in control xenografts.Implications: Collectively, these
      findings demonstrate the plasticity of paracrine growth factor receptor signaling
      in vivo and urge for prudency with in vitro drug-testing strategies to validate
      monotherapies. Mol Cancer Res; 15(11); 1587-97. (c)2017 AACR.

PMID- 28751465
TI  - India cracks down on clinics offering stem cell therapy and blood cord banking.

PMID- 28751464
TI  - Effects of electroacupuncture stimulation at different spinal segmental levels in
      a rat model of diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus (DM) is associated with high morbidity, mortality
      and economic cost. Studies have shown that acupuncture can improve many symptoms
      of DM. OBJECTIVES: To examine for differences in effects of electroacupuncture
      (EA) stimulation at Weiwanxiashu, BL15 and BL23 in the streptozotocin (STZ)
      induced DM rat model, to help guide clinical selection of acupuncture points.
      METHODS: 90 male rats weighing 160A+/-5 g were used. 12 rats were control fed
      (Normal group) and 78 were fed a high-fat high-sugar diet for 8 weeks and
      underwent intraperitoneal STZ injection to model DM. 60 animals that met
      modelling criteria were randomly divided into an untreated DM group and four
      groups receiving EA at Weiwanxiashu (DM+WWX group), BL15 (DM+BL15 group), BL23
      (DM+BL23 group) or a non-traditional acupuncture point on the tail (DM+Tail
      group). Fasting blood glucose, total cholesterol (TC), triglyceride (TG), high
      density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL
      C) and insulin levels were determined and an oral glucose tolerance test (OGTT)
      performed. RESULTS: EA at Weiwanxiashu had a glucose-lowering effect on the 21st
      and 28th days, decreased TC, TG and LDL-C levels, increase insulin levels and
      improved glucose tolerance. EA at BL15 had a glucose-lowering effect on the7th,
      14th and 21st days of intervention but did not impact lipids, insulin or OGTT
      parameters. EA at BL23 or on the tail had no significant effects. CONCLUSION: EA
      at Weiwanxiashu and BL15 had differential effects on metabolic markers in the STZ
      induced rat model of DM. These effects may be explained neuroanatomically by
      variations in the segmental innervation of the tissues at these locations.

PMID- 28751463
TI  - Dual Src Kinase/Pretubulin Inhibitor KX-01, Sensitizes ERalpha-negative Breast
      Cancers to Tamoxifen through ERalpha Reexpression.
AB  - Unlike breast cancer that is positive for estrogen receptor-alpha (ERalpha),
      there are no targeted therapies for triple-negative breast cancer (TNBC). ERalpha
      is silenced in TNBC through epigenetic changes including DNA methylation and
      histone acetylation. Restoring ERalpha expression in TNBC may sensitize patients
      to endocrine therapy. Expression of c-Src and ERalpha are inversely correlated in
      breast cancer suggesting that c-Src inhibition may lead to reexpression of
      ERalpha in TNBC. KX-01 is a peptide substrate-targeted Src/pretubulin inhibitor
      in clinical trials for solid tumors. KX-01 (1 mg/kg body weight-twice daily)
      inhibited growth of tamoxifen-resistant MDA-MB-231 and MDA-MB-157 TNBC xenografts
      in nude mice that was correlated with Src kinase inhibition. KX-01 also increased
      ERalpha mRNA and protein, as well as increased the ERalpha targets progesterone
      receptor (PR), pS2 (TFF1), cyclin D1 (CCND1), and c-myc (MYC) in MDA-MB-231 and
      MDA-MB-468, but not MDA-MB-157 xenografts. MDA-MB-231 and MDA-MB-468 tumors
      exhibited reduction in mesenchymal markers (vimentin, beta-catenin) and increase
      in epithelial marker (E-cadherin) suggesting mesenchymal-to-epithelial transition
      (MET). KX-01 sensitized MDA-MB-231 and MDA-MB-468 tumors to tamoxifen growth
      inhibition and tamoxifen repression of the ERalpha targets pS2, cyclin D1, and c
      myc. Chromatin immunoprecipitation (ChIP) of the ERalpha promoter in KX-01
      treated tumors demonstrated enrichment of active transcription marks (acetyl-H3,
      acetyl-H3Lys9), dissociation of HDAC1, and recruitment of RNA polymerase II.
      Methylation-specific PCR and bisulfite sequencing demonstrated no alteration in
      ERalpha promoter methylation by KX-01. These data demonstrate that in addition to
      Src kinase inhibition, peptidomimetic KX-01 restores ERalpha expression in TNBC
      through changes in histone acetylation that sensitize tumors to
      tamoxifen.Implications: Src kinase/pretubulin inhibitor KX-01 restores functional
      ERalpha expression in ERalpha- breast tumors, a novel treatment strategy to treat
      triple-negative breast cancer. Mol Cancer Res; 15(11); 1491-502. (c)2017 AACR.

PMID- 28751466
TI  - Treatment-Refractory Sternocostoclavicular Hyperostosis.
AB  - Sternocostoclavicular hyperostosis (SCCH) is an infrequent chronic inflammatory
      disorder of the axial skeleton of unknown origin. SCCH goes often unrecognized
      due to a low level of awareness for the disorder. It typically presents with
      relapsing and remitting pain in the shoulder, neck, and anterior chest wall area
      with occasional swelling and tenderness of the sternoclavicular area. The
      diagnosis is confirmed radiologically by sclerosis and hyperostosis of the
      sternoclavicular joints. There have been several reports in which intravenous
      bisphosphonates and tumor necrosis factor-inhibitors have shown reasonable
      efficacy in the treatment of this disorder. We report a patient with a long
      history of SCCH in whom pamidronate 60 mg intravenously every 3 months for 3
      years failed to reduce symptom severity and improve radiologic findings.

PMID- 28751467
TI  - Recurrent Thrombosis in Patients with Antiphospholipid Syndrome Receiving Newer
      Oral Anticoagulants: A Case Report and Review of Literature.
AB  - We present the case of a patient with primary APS who had a recurrence of
      thrombotic event while on treatment with rivaroxaban and had to be restarted on
      warfarin. The current literature on recurrence of thrombotic events in patients
      with antiphospholipid syndrome (APS) treated with newer oral anticoagulants
      (NOAC) is also reviewed. Relevant case reports and case series were identified by
      searching the Medline database using the key words antiphospholipid syndrome,
      anticoagulants and names of the NOACs, and data on individual patients was
      abstracted. We identified several reports on the failure of newer anticoagulants
      in APS, as well as cases and clinical trial results reporting efficacy. We
      conclude that treatment strategies for APS should be tailored cautiously when
      using NOACs.

PMID- 28751468
TI  - Overcoming Operational Challenges to Ebola Case Investigation in Sierra Leone.
AB  - The Ebola virus disease (EVD) epidemic that hit West Africa in 2013 was the worst
      outbreak of EVD in recorded history. While much has been published regarding the
      international and national-level EVD responses, there is a dearth of literature
      on district-level coordination and operational structures, successes, and
      failures. This article seeks to understand how the EVD response unfolded at the
      district level, namely the challenges to operationalizing EVD surveillance over
      the course of the outbreak in Port Loko and Kambia districts of Sierra Leone. We
      present here GOAL Global's understanding of the fundamental challenges to case
      investigation operations during the EVD response, including environmental and
      infrastructural, sociocultural, and political and organizational challenges, with
      insight complemented by a survey of 42 case investigators. Major challenges
      included deficiencies in transportation and communication resources, low morale
      and fatigue among case investigators, mismanagement of data, mistrust among
      communities, and leadership challenges. Without addressing these operational
      challenges, technical surveillance solutions are difficult to implement and hold
      limited relevance, due to the poor quality and quantity of data being collected.
      The low prioritization of operational needs came at a high cost. To mediate this,
      GOAL addressed these operational challenges by acquiring critical transportation
      and communication resources to facilitate case investigation, including vehicles,
      boats, fuel, drivers, phones, and closed user groups; addressing fatigue and low
      morale by hiring more case investigators, making timely payments, arranging for
      time off, and providing meals and personal protective equipment; improving data
      tracking efforts through standard operating procedures, training, and mentorship
      to build higher-quality case histories and make it easier to access information;
      strengthening trust in communities by ensuring familiarity and consistency of
      case investigators; and improving operational leadership challenges through
      meetings and regular coordination, establishing an active surveillance strategy
      in Port Loko, and conducting an after-action review. Resolving or addressing
      these challenges was of primary importance, and requisite for the implementation
      of technical epidemiological complements to EVD case investigation.

PMID- 28751469
TI  - Ethics consultation in paediatric and adult emergency departments: an assessment
      of clinical, ethical, learning and resource needs.
AB  - OBJECTIVE: We sought to understand ethics and education needs of emergency nurses
      and physicians in paediatric and adult emergency departments (EDs) in order to
      build ethics capacity and provide a foundation for the development of an ethics
      education programme. METHODS: This was a prospective cross-sectional survey of
      all staff nurses and physicians in three tertiary care EDs. The survey tool,
      called Clinical Ethics Needs Assessment Survey, was pilot tested on a similar
      target audience for question content and clarity. RESULTS: Of the 123
      participants surveyed, 72% and 84% of nurses and physicians fully/somewhat agreed
      with an overall positive ethical climate, respectively. 69% of participants
      reported encountering daily or weekly ethical challenges. Participants expressed
      the greatest need for additional support to address moral distress (16%),
      conflict management with patients or families (16%) and resource issues (15%). Of
      the 23 reported occurrences of moral distress, 61% were associated with
      paediatric mental health cases. When asked how the ethics consultation service
      could be used in the ED, providing education to teams (42%) was the most desired
      method. CONCLUSIONS: Nurses report a greater need for ethics education and
      resources compared with their physician colleagues. Ethical challenges in
      paediatric EDs are more prevalent than adult EDs and nurses voice specific moral
      distress that are different than adult EDs. These results highlight the need for
      a suitable educational strategy, which can be developed in collaboration with the
      leadership of each ED and team of hospital ethicists.

PMID- 28751470
TI  - Paneth cells secrete lysozyme via secretory autophagy during bacterial infection
      of the intestine.
AB  - Intestinal Paneth cells limit bacterial invasion by secreting antimicrobial
      proteins, including lysozyme. However, invasive pathogens can disrupt the Golgi
      apparatus, interfering with secretion and compromising intestinal antimicrobial
      defense. Here we show that during bacterial infection, lysozyme is rerouted via
      secretory autophagy, an autophagy-based alternative secretion pathway. Secretory
      autophagy was triggered in Paneth cells by bacteria-induced endoplasmic reticulum
      (ER) stress, required extrinsic signals from innate lymphoid cells, and limited
      bacterial dissemination. Secretory autophagy was disrupted in Paneth cells of
      mice harboring a mutation in autophagy gene Atg16L1 that confers increased risk
      for Crohn's disease in humans. Our findings identify a role for secretory
      autophagy in intestinal defense and suggest why Crohn's disease is associated
      with genetic mutations that affect both the ER stress response and autophagy.

PMID- 28751471
TI  - Structure of a symmetric photosynthetic reaction center-photosystem.
AB  - Reaction centers are pigment-protein complexes that drive photosynthesis by
      converting light into chemical energy. It is believed that they arose once from a
      homodimeric protein. The symmetry of a homodimer is broken in heterodimeric
      reaction-center structures, such as those reported previously. The 2.2-angstrom
      resolution x-ray structure of the homodimeric reaction center-photosystem from
      the phototroph Heliobacterium modesticaldum exhibits perfect C2 symmetry. The
      core polypeptide dimer and two small subunits coordinate 54 bacteriochlorophylls
      and 2 carotenoids that capture and transfer energy to the electron transfer chain
      at the center, which performs charge separation and consists of 6
      (bacterio)chlorophylls and an iron-sulfur cluster; unlike other reaction centers,
      it lacks a bound quinone. This structure preserves characteristics of the
      ancestral reaction center, providing insight into the evolution of
      photosynthesis.

PMID- 28751473
TI  - Identification of the macrophage-specific promoter signature in FANTOM5 mouse
      embryo developmental time course data.
AB  - The FANTOM5 consortium used cap analysis of gene expression (CAGE) to analyze the
      time course of gene expression over development from 11 days postcoitum (dpc) to
      adult in 16 developing organs and the whole body of the mouse. Every tissue in
      the body contains a large number of resident macrophages that initially
      infiltrate the embryo from the yolk sac. These cells contribute to organogenesis,
      and their functions diversify during development as they acquire tissue-specific
      adaptations. In each of the FANTOM5 time courses, the expression of known
      macrophage-specific genes, including CSF1 receptor (Csf1r), epidermal growth
      factor-like module-containing mucin-like hormone receptor-like 1 (Emr1), and mer
      receptor tyrosine kinase (Mertk), was readily detectable and increased with time.
      We reasoned that genes expressed by macrophages would be strongly correlated in
      their expression with these known markers and might vary between tissues. We used
      the network analysis tool, Miru, to extract the sets of coexpressed genes from
      the time course and identified a core set of coexpressed genes attributable to
      embryonic macrophages, including some, such as dehydrogenase/reductase 3 (Dhrs3),
      that may have unique functions in development. The FANTOM5 data also detected the
      appearance of tissue-specific macrophage-expressed genes, such as T cell Ig and
      mucin domain-containing 4 (Timd4) and V-set and Ig domain-containing 4 (Vsig4) in
      liver and sialic acid-binding Ig-like lectin 5 (Siglec5) in lung, and confirmed
      that macrophage content increases with time in each organ as the proliferative
      phases end, and tissue-specific gene-expression increases. The FANTOM5 data are
      available on a comprehensive browser (http://fantom.gsc.riken.jp/zenbu/), which
      provides a resource for the study of macrophage transcriptional regulation and
      roles in mouse development.

PMID- 28751472
TI  - Parkinson disease-associated LRRK2 G2019S transgene disrupts marrow myelopoiesis
      and peripheral Th17 response.
AB  - Parkinson's disease (PD) is a neurodegenerative disease, whereas Crohn's disease
      is an inflammatory bowel disease. Interestingly, polymorphisms in the LRRK2 gene
      have been identified as risk factors for both diseases. LRRK2 G2019S is the most
      prevalent mutation found in PD. To gain insights into the role of the LRRK2
      G2019S gene on the development and activation of the immune system in the brain
      gut axis, we investigated the effect of LRRK2 G2019S on bone marrow myeloid
      progenitors and myeloid cell function in the periphery. We used bacterial
      artificial chromosome transgenic rats harboring the human LRRK2 G2019S gene.
      LRRK2 G2019S transgene decreased the numbers of monocytic and granulocytic
      progenitors in the bone marrow. However, the numbers of peripheral, immature
      myeloid cells with suppressive activity were increased in the gut and blood
      circulation of LRRK2 G2019S compared with control rats in various acute and
      chronic inflammatory responses. In inflammatory conditions, Th17 cell activity
      was suppressed, but tissue-associated phylum Bacteroidetes was abnormally
      increased in the intestine of LRRK2 G2019S rats. The abnormally expanded myeloid
      cells because of the LRRK2 G2019S gene were highly suppressive on Th17 cell
      differentiation. Moreover, we found that inhibition of LRRK2 kinase affects
      myeloid progenitors and myeloid cell differentiation. Taken together, the results
      indicate that abnormal LRRK2 activity can alter bone marrow myelopoiesis,
      peripheral myeloid cell differentiation, and intestinal immune homeostasis. These
      findings may have ramifications in immune and inflammatory responses in patients
      with LRRK2 abnormalities.

PMID- 28751474
TI  - HIV agenda must be prioritised to reduce deaths from AIDS in sub-Saharan Africa.

PMID- 28751475
TI  - Recent Trends in Ovarian Cancer Incidence and Relative Survival in the United
      States by Race/Ethnicity and Histologic Subtypes.
AB  - Background: Incidence and survival rates of nonserous epithelial ovarian cancer
      in racial/ethnic minorities remain relatively unknown in the United States. We
      examined the trends in incidence and survival rates for epithelial ovarian cancer
      by histologic subtypes and race/ethnicity.Methods: Ovarian cancer incidence and
      mortality data from 2000 to 2013 were obtained from the Surveillance,
      Epidemiology, and End Results database. Age-adjusted incidence rate, incidence
      rate ratio, and annual percentage changes (APC) were calculated by histology and
      race/ethnicity subgroups and stratified by age at diagnosis. Five-year relative
      survival rates were calculated by stage and race/ethnicity.Results: A small but
      significant decrease in incidence rates was seen in non-Hispanic white (NHW), non
      Hispanic black (NHB), and Hispanic women (APC -1.58, -0.84, and -1.31,
      respectively), while incidence rates remained relatively stable in Asian women
      (APC -0.37). With exception of significant increase in the incidence rate of
      clear cell carcinoma among Asian woman (APC 1.85), an overall trend toward
      decreasing incidence rates was seen across histologic subtypes and age-strata,
      although not all results were statistically significant. Compared with NHW women,
      NHB women experienced poorer 5-year survival at every stage across histologic
      subtypes, while Hispanic and Asian women had equivalent or better
      survival.Conclusions: Over the last decade, incidence rates of epithelial ovarian
      cancer in the United States have decreased or remained stable across race/ethnic
      and histologic subgroups, except for clear cell carcinoma. Survival remains
      poorest among NHB women.Impact: Comparative histologic subtype distribution and
      incidence trends do not explain the ovarian cancer survival disparity
      disproportionately affecting NHB women. Cancer Epidemiol Biomarkers Prev; 26(10);
      1511-8. (c)2017 AACR.

PMID- 28751476
TI  - Rural-Urban Differences in Cancer Incidence and Trends in the United States.
AB  - Background: Cancer incidence and mortality rates in the United States are
      declining, but this decrease may not be observed in rural areas where residents
      are more likely to live in poverty, smoke, and forego cancer screening. However,
      there is limited research exploring national rural-urban differences in cancer
      incidence and trends.Methods: We analyzed data from the North American
      Association of Central Cancer Registries' public use dataset, which includes
      population-based cancer incidence data from 46 states. We calculated age-adjusted
      incidence rates, rate ratios, and annual percentage change (APC) for: all cancers
      combined, selected individual cancers, and cancers associated with tobacco use
      and human papillomavirus (HPV). Rural-urban comparisons were made by demographic,
      geographic, and socioeconomic characteristics for 2009 to 2013. Trends were
      analyzed for 1995 to 2013.Results: Combined cancers incidence rates were
      generally higher in urban populations, except for the South, although the urban
      decline in incidence rate was greater than in rural populations (10.2% vs. 4.8%,
      respectively). Rural cancer disparities included higher rates of tobacco
      associated, HPV-associated, lung and bronchus, cervical, and colorectal cancers
      across most population groups. Furthermore, HPV-associated cancer incidence rates
      increased in rural areas (APC = 0.724, P < 0.05), while temporal trends remained
      stable in urban areas.Conclusions: Cancer rates associated with modifiable risks
      tobacco, HPV, and some preventive screening modalities (e.g., colorectal and
      cervical cancers)-were higher in rural compared with urban populations.Impact:
      Population-based, clinical, and/or policy strategies and interventions that
      address these modifiable risk factors could help reduce cancer disparities
      experienced in rural populations. Cancer Epidemiol Biomarkers Prev; 27(11); 1265
      74. (c)2017 AACR.

PMID- 28751477
TI  - Associations of Coffee Drinking and Cancer Mortality in the Cancer Prevention
      Study-II.
AB  - Background: Associations of coffee consumption with cancer mortality are
      inconsistent for many types of cancer, and confounding by smoking is an important
      concern.Methods: Cox proportional hazards regression was used to estimate
      multivariable-adjusted HRs for coffee consumption associated with death from all
      cancers combined and from specific cancer types among 922,896 Cancer Prevention
      Study-II participants ages 28-94 years who completed a four-page questionnaire
      and were cancer free at baseline in 1982.Results: During follow-up through 2012,
      there were 118,738 cancer-related deaths. There was a nonlinear association
      between coffee consumption and all-cancer death among current smokers and former
      smokers and no association among never smokers. Among nonsmokers, a 2 cup/day
      increase in coffee consumption was inversely associated with death from
      colorectal [HR = 0.97; 95% confidence interval (CI) 0.95-0.99], liver [HR = 0.92;
      95% CI, 0.88-0.96], and female breast (HR = 0.97; 95% CI, 0.94-0.99) cancers, and
      positively associated with esophageal cancer-related death (HR = 1.07; 95% CI,
      1.02-1.12). For head and neck cancer, a nonlinear inverse association was
      observed starting at 2-3 cups per day (HR = 0.72; 95% CI, 0.55-0.95), with
      similar associations observed at higher levels of consumption.Conclusions: These
      findings are consistent with many other studies that suggest coffee drinking is
      associated with a lower risk of colorectal, liver, female breast, and head and
      neck cancer. The association of coffee consumption with higher risk of esophageal
      cancer among nonsmokers in our study should be confirmed.Impact: These results
      underscore the importance of assessing associations between coffee consumption
      and cancer mortality by smoking status. Cancer Epidemiol Biomarkers Prev; 26(10);
      1477-86. (c)2017 AACR.

PMID- 28751479
TI  - An uncommon right iliac fossa mass in an older woman.

PMID- 28751478
TI  - Novel Gene and Network Associations Found for Acute Lymphoblastic Leukemia Using
      Case-Control and Family-Based Studies in Multiethnic Populations.
AB  - Background: Acute lymphoblastic leukemia (ALL) is the most common childhood
      cancer, suggesting that germline variants influence ALL risk. Although multiple
      genome-wide association (GWA) studies have identified variants predisposing
      children to ALL, it remains unclear whether genetic heterogeneity affects ALL
      susceptibility and how interactions within and among genes containing ALL
      associated variants influence ALL risk.Methods: Here, we jointly analyzed two
      published datasets of case-control GWA summary statistics along with germline
      data from ALL case-parent trios. We used the gene-level association method
      PEGASUS to identify genes with multiple variants associated with ALL. We then
      used PEGASUS gene scores as input to the network analysis algorithm HotNet2 to
      characterize the genomic architecture of ALL.Results: Using PEGASUS, we confirmed
      associations previously observed at genes such as ARID5B, IKZF1, CDKN2A/2B, and
      PIP4K2A, and we identified novel candidate gene associations. Using HotNet2, we
      uncovered significant gene subnetworks that may underlie inherited ALL risk: a
      subnetwork involved in B-cell differentiation containing the ALL-associated gene
      CEBPE, and a subnetwork of homeobox genes, including MEIS1Conclusions: Gene and
      network analysis uncovered loci associated with ALL that are missed by GWA
      studies, such as MEIS1 Furthermore, ALL-associated loci do not appear to interact
      directly with each other to influence ALL risk, and instead appear to influence
      leukemogenesis through multiple, complex pathways.Impact: We present a new
      pipeline for post hoc analysis of association studies that yields new insight
      into the etiology of ALL and can be applied in future studies to shed light on
      the genomic underpinnings of cancer. Cancer Epidemiol Biomarkers Prev; 26(10);
      1531-9. (c)2017 AACR.

PMID- 28751480
TI  - CQC boss heads for the exit: "I've always told it as it is".

PMID- 28751481
TI  - Recruitment and retention in a 10-month social network-based intervention
      promoting diabetes self-management in socioeconomically deprived patients: a
      qualitative process evaluation.
AB  - OBJECTIVES: Socioeconomically deprived patients with type 2 diabetes often face
      challenges with self-management, resulting in more diabetes-related
      complications. However, these groups are often under-represented in self
      management interventions. Evidence on effective recruitment and retention
      strategies is growing, but lacking for intensive self-management interventions.
      This study aims to explore recruitment, retention and effective intervention
      strategies in a 10-month group-based intervention among Dutch, Moroccan, Turkish
      and Surinamese patients from socioeconomically deprived neighbourhoods. METHODS:
      Participants were recruited through general practitioners (GPs) and participated
      in a 10-month social network-based intervention (10 groups, n=69): Powerful
      Together with Diabetes. This intervention also targeted the significant others of
      participants and aimed to increase social support for self-management and to
      decrease social influences hindering self-management. A qualitative process
      evaluation was conducted. Retention was measured using log books kept by group
      leaders. Further, we conducted 17 in-depth interviews with participants
      (multiethnic sample) and 18 with group leaders. Interviews were transcribed,
      coded and analysed using framework analyses. RESULTS: The GP's letter and
      reminder calls, an informational meeting and the intervention's informal nature
      facilitated recruitment. During the first months, positive group atmosphere, the
      intervention's perceived usefulness, opportunities to socialise and a reduction
      in practical barriers facilitated retention. After the first months, conflicting
      responsibilities and changes in the intervention's nature and planning hindered
      retention. Calls from group leaders and the prospect of a diploma helped
      participants overcome these barriers. CONCLUSION: To promote retention in lengthy
      self-management interventions, it seems important that patients feel they are
      going on an outing to a social gathering that is enjoyable, recreational, useful
      and easy to attend. However, rewards and intensive personal recruitment and
      retention strategies remained necessary throughout the entire intervention
      period. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR1886; Results.

PMID- 28751482
TI  - Associations of anthropometry since birth with sagittal posture at age 7 in a
      prospective birth cohort: the Generation XXI Study.
AB  - OBJECTIVES: Adult sagittal posture is established during childhood and
      adolescence. A flattened or hypercurved spine is associated with poorer
      musculoskeletal health in adulthood. Although anthropometry from birth onwards is
      expected to be a key influence on sagittal posture design, this has never been
      assessed during childhood. Our aim was to estimate the association between body
      size throughout childhood with sagittal postural patterns at age 7. DESIGN:
      Prospective cohort study. SETTING AND PARTICIPANTS: A subsample of 1029 girls and
      1101 boys taking part in the 7-year-old follow-up of the birth cohort Generation
      XXI (Porto, Portugal) was included. We assessed the associations between
      anthropometric measurements (weight, height and body mass index) at birth, 4 and
      7 years of age and postural patterns at age 7. Postural patterns were defined
      using latent profile analysis, a probabilistic model-based technique which allows
      for simultaneously including anthropometrics as predictors of latent profiles by
      means of logistic regression. RESULTS: Postural patterns identified were sway,
      flat and "neutral to hyperlordotic"in girls, and "sway to neutral", flat and
      hyperlordotic in boys; with flat and hyperlordotic postures representing a
      straightened and a rounded spine, respectively. In both girls and boys, higher
      weight was associated with lower odds of a flat pattern compared with a
      sway/"sway to neutral"pattern, with stronger associations at older ages: for
      example, ORs were 0.68 (95% CI 0.53 to 0.88) per SD increase in birth weight and
      0.36 (95% CI 0.19 to 0.68) per SD increase in weight at age 7 in girls, with
      similar findings in boys. Boys with higher ponderal index at birth were more
      frequently assigned to the hyperlordotic pattern (OR=1.44 per SD; p=0.043).
      CONCLUSIONS: Our findings support a prospective sculpting role of body size and
      therefore of load on musculoskeletal spinopelvic structures, with stronger
      associations as children get older.

PMID- 28751483
TI  - Respiratory syncytial virus: a systematic scientometric analysis of the global
      publication output and the gender distribution of publishing authors.
AB  - OBJECTIVE: Worldwide, the respiratory syncytial virus (RSV) represents the
      predominant viral agent causing bronchiolitis and pneumonia in children. To
      conduct research and tackle existing healthcare disparities, RSV-related research
      activities around the globe need to be described. Hence, we assessed the
      associated scientific output (represented by research articles) by geographical,
      chronological and socioeconomic criteria and analysed the authors publishing in
      the field by gender. Also, the 15 most cited articles and the most prolific
      journals were identified for RSV research. DESIGN: Retrospective, descriptive
      study. SETTING: The NewQIS (New Quality and Quantity Indices in Science) platform
      was employed to identify RSV-related articles published in the Web of Science
      until 2013. We performed a numerical analysis of all articles, and examined
      citation-based aspects (eg, citation rates); results were visualised by density
      equalising mapping tools. RESULTS: We identified 4600 RSV-related articles. The
      USA led the field; US-American authors published 2139 articles (46.5%% of all
      identified articles), which have been cited 83 000 times. When output was related
      to socioeconomic benchmarks such as gross domestic product or Research and
      Development expenditures, Guinea-Bissau, The Gambia and Chile were ranked in
      leading positions. A total of 614 articles on RSV (13.34% of all articles) were
      attributed to scientific collaborations. These were primarily established between
      high-income countries. The gender analysis indicated that male scientists
      dominated in all countries except Brazil. CONCLUSIONS: The majority of RSV
      related research articles originated from high-income countries whereas
      developing nations showed only minimal publication productivity and were barely
      part of any collaborative networks. Hence, research capacity in these nations
      should be increased in order to assist in addressing inequities in resource
      allocation and the clinical burden of RSV in these countries.

PMID- 28751484
TI  - Medication incidents in primary care medicine: a prospective study in the Swiss
      Sentinel Surveillance Network (Sentinella).
AB  - OBJECTIVES: To describe the type, frequency, seasonal and regional distribution
      of medication incidents in primary care in Switzerland and to elucidate possible
      risk factors for medication incidents. DESIGN: Prospective surveillance study.
      SETTING: Swiss primary healthcare, Swiss Sentinel Surveillance Network.
      PARTICIPANTS: Patients with drug treatment who experienced any erroneous event
      related to the medication process and interfering with normal treatment course,
      as judged by their physician. The 180 physicians in the study were general
      practitioners or paediatricians participating in the Swiss Federal Sentinel
      reporting system in 2015. OUTCOMES: Primary: medication incidents; secondary:
      potential risk factors like age, gender, polymedication, morbidity, care
      dependency, previous hospitalisation. RESULTS: The mean rates of detected
      medication incidents were 2.07 per general practitioner per year (46.5 per 1 00
      000 contacts) and 0.15 per paediatrician per year (2.8 per 1 00 000 contacts),
      respectively. The following factors were associated with medication incidents
      (OR, 95% CI): higher age 1.004 per year (1.001; 1.006), care by community nurse
      1.458 (1.025; 2.073) and care by an institution 1.802 (1.399; 2.323), chronic
      conditions 1.052 (1.029; 1.075) per condition, medications 1.052 (1.030; 1.074)
      per medication, as well as Thurgau Morbidity Index for stage 4: 1.292 (1.004;
      1.662), stage 5: 1.420 (1.078; 1.868) and stage 6: 1.680 (1.178; 2.396),
      respectively. Most cases were linked to an incorrect dosage for a given patient,
      while prescription of an erroneous medication was the second most common error.
      CONCLUSIONS: Medication incidents are common in adult primary care, whereas they
      rarely occur in paediatrics. Older and multimorbid patients are at a particularly
      high risk for medication incidents. Reasons for medication incidents are diverse
      but often seem to be linked to communication problems.

PMID- 28751485
TI  - Herbal medications for surgical patients: a systematic review protocol.
AB  - INTRODUCTION: Postoperative nausea and vomiting (PONV) affect approximately 80%
      of surgical patients and is associated with increased length of hospital stay and
      systemic costs. Preoperative and postoperative pain, anxiety and depression are
      also commonly reported. Recent evidence regarding their safety and effectiveness
      has not been synthesised. The aim of this systematic review is to evaluate the
      efficacy and safety of herbal medications for the treatment and prevention of
      anxiety, depression, pain and PONV in patients undergoing laparoscopic,
      obstetrical/gynaecological and cardiovascular surgical procedures. METHODS AND
      ANALYSIS: The following electronic databases will be searched up to 1 October
      2016 without language or publication status restrictions: CENTRAL, MEDLINE,
      EMBASE, CINAHL, Web of Science and LILACS. Randomised clinical trials enrolling
      adult surgical patients undergoing laparoscopic, obstetrical/gynaecological and
      cardiovascular surgeries and managed with herbal medication versus a control
      group (placebo, no intervention or active control) prophylactically or
      therapeutically will be considered eligible. Outcomes of interest will include
      the following: anxiety, depression, pain, nausea and vomiting. A team of
      reviewers will complete title and abstract screening and full-text screening for
      identified hits independently and in duplicate. Data extraction, risk of bias
      assessments and evaluation of the overall quality of evidence for each relevant
      outcome reported will be conducted independently and in duplicate using the
      Grading of Recommendations Assessment Development and Evaluation classification
      system. Dichotomous data will be summarised as risk ratios; continuous data will
      be summarised as standard average differences with 95% CIs. ETHICS AND
      DISSEMINATION: This is one of the first efforts to systematically summarise
      existing evidence evaluating the use of herbal medications in laparoscopic,
      obstetrical/gynaecological and cardiovascular surgical patients. The findings of
      this review will be disseminated through peer-reviewed publications and
      conference presentations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42016042838.

PMID- 28751486
TI  - Profiles of children's social-emotional health at school entry and associated
      income, gender and language inequalities: a cross-sectional population-based
      study in British Columbia, Canada.
AB  - OBJECTIVES: Early identification of distinct patterns of child social-emotional
      strengths and vulnerabilities has the potential to improve our understanding of
      child mental health and well-being; however, few studies have explored natural
      groupings of indicators of child vulnerability and strengths at a population
      level. The purpose of this study was to examine heterogeneity in the patterns of
      young children's social and emotional health and investigate the extent to which
      sociodemographic characteristics were associated. DESIGN: Cross-sectional study
      based on a population-level cohort. SETTING: All kindergarten children attending
      public schools between 2004 and 2007 in British Columbia (BC), Canada.
      PARTICIPANTS: 35 818 kindergarten children (age of 5 years) with available linked
      data from the Early Development Instrument (EDI), BC Ministry of Health and BC
      Ministry of Education. OUTCOME MEASURE: We used latent profile analysis (LPA) to
      identify distinct profiles of social-emotional health according to children's
      mean scores across eight social-emotional subscales on the EDI, a teacher-rated
      measure of children's early development. Subscales measured children's overall
      social competence, responsibility and respect, approaches to learning, readiness
      to explore, prosocial behaviour, anxiety, aggression and hyperactivity. RESULTS:
      Six social-emotional profiles were identified: (1) overall high social-emotional
      functioning, (2) inhibited-adaptive (3) uninhibited-adaptive, (4) inhibited
      disengaged, (5) uninhibited-aggressive/hyperactive and (6) overall low social
      emotional functioning. Boys, children with English as a second language (ESL)
      status and children with lower household income had higher odds of membership to
      the lower social-emotional functioning groups; however, this association was less
      negative among boys with ESL status. CONCLUSIONS: Over 40% of children exhibited
      some vulnerability in early social-emotional health, and profiles were associated
      with sociodemographic factors. Approximately 9% of children exhibited multiple co
      occurring vulnerabilities. This study adds to our understanding of population
      level distributions of children's early social-emotional health and identifies
      profiles of strengths and vulnerabilities that can inform future intervention
      efforts.

PMID- 28751487
TI  - Ability to join the workforce and work productivity among drug users under
      methadone maintenance treatment in a mountainous area of Northern Vietnam: a
      cross-sectional study.
AB  - OBJECTIVES: A major measure of treatment success for drug users undergoing
      rehabilitation is the ability to enter the workforce and generate income. This
      study examines the absenteeism and productivity among people who inject drugs
      (PWID) enrolled in methadone maintenance treatment (MMT) in Northern Vietnam.
      SETTING: We conducted a cross-sectional study in two clinics in Tuyen Quang
      province. PARTICIPANTS: A total of 241 patients enrolled in MMT. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Patients' work productivity was measured using the
      WPAI-GH instrument (Work Productivity and Activity Impairment Questionnaire:
      General Health V2.0). We also collected additional characteristics about
      participants' employment history, such as proficient jobs, whether they actively
      found a new job and be accepted by employers. RESULTS: Most of the participants
      (>90%) were employed at the time of the study. Rates of absenteeism (missed
      work), presenteeism (impairment while working) and overall loss of productivity
      were 15.8%, 5.6% and 11.2%, respectively, as measured by the WPAI-GH
      questionnaire. The most proficient job was 'freelancer' (17.5%), followed by
      'blue-collar worker' (10.6%) and 'farmer' (10.2%). Only 26.8% of patients
      reported that they actively sought jobs in the past. About half of them had been
      refused by employers because of their drug use history and/or HIV status. We
      found no statistically significant difference between patients enrolled in MMT
      for <1 year and those who had been enrolled >1 year. Factors associated with
      higher work productivity included not endorsing problems in mobility, self-care
      or pain; being HIV-negative and having greater MMT treatment adherence.
      CONCLUSION: Our study highlights the high employment rate and work productivity
      among PWID in MMT programmes in remote areas of Northern Vietnam. The results can
      help to improve the quality and structure of MMT programmes across Vietnam and in
      other countries.

PMID- 28751488
TI  - Guideline recommendations and antimicrobial resistance: the need for a change.
AB  - OBJECTIVES: Antimicrobial resistance has become a global burden for which
      inappropriate antimicrobial use is an important contributing factor. Any
      decisions on the selection of antibiotics use should consider their effects on
      antimicrobial resistance. The objective of this study was to assess the extent to
      which antibiotic prescribing guidelines have considered resistance patterns when
      making recommendations for five highly prevalent infectious syndromes. DESIGN: We
      used Medline searches complemented with extensive use of Web engine to identify
      guidelines on empirical treatment of community-acquired pneumonia, urinary tract
      infections, acute otitis media, rhinosinusitis and pharyngitis. We collected data
      on microbiology and resistance patterns and identified discrete pattern
      categories. We assessed the extent to which recommendations considered
      resistance, in addition to efficacy and safety, when recommending antibiotics.
      RESULTS: We identified 135 guidelines, which reported a total of 251
      recommendations. Most (103/135, 79%) were from developed countries. Community
      acquired pneumonia was the syndrome mostly represented (51, 39%). In only 16
      (6.4%) recommendations, selection of empirical antibiotic was discussed in
      relation to resistance and specific microbiological data. In a further 69 (27.5%)
      recommendations, references were made in relation to resistance, but the attempt
      was inconsistent. Across syndromes, 12 patterns of resistance with implications
      on recommendations were observed. 50% to 75% of recommendations did not attempt
      to set recommendation in the context of these patterns. CONCLUSION: There is
      consistent evidence that guidelines on empirical antibiotic use did not routinely
      consider resistance in their recommendations. Decision-makers should analyse and
      report the extent of local resistance patterns to allow better decision-making.

PMID- 28751489
TI  - Common attributes in retired professional cricketers that may enhance or hinder
      quality of life after retirement: a qualitative study.
AB  - OBJECTIVES: Retired professional cricketers shared unique experiences and may
      possess specific psychological attributes with potential to influence quality of
      life (QOL). Additionally, pain and osteoarthritis can be common in retired
      athletes which may negatively impact QOL. However, QOL in retired athletes is
      poorly understood. This study explores the following questions from the personal
      perspective of retired cricketers: How do retired cricketers perceive and
      experience musculoskeletal pain and function in daily life? Are there any
      psychological attributes that might enhance or hinder retired cricketers' QOL?
      DESIGN: A qualitative study using semistructured interviews, which were subject
      to inductive, thematic analysis. A data-driven, iterative approach to data coding
      was employed. SETTING: All participants had lived and played professional cricket
      in the UK and were living in the UK or abroad at the time of interview.
      PARTICIPANTS: Eighteen male participants, aged a mean 57+/-11 (range 34-77) years
      had played professional cricket for a mean 12+/-7 seasons and had been retired
      from professional cricket on average 23+/-9 years. RESULTS: Fifteen participants
      reported pain or joint difficulties and all but one was satisfied with their QOL.
      Most retired cricketers reflected on experiences during their cricket career that
      may be associated with the psychological attributes that these individuals
      shared, including resilience and a positive attitude. Additional attributes
      included a high sense of body awareness, an ability to self-manage pain and adapt
      lifestyle choices to accommodate physical limitations. Participants felt
      fortunate and proud to have played professional cricket, which may have further
      contributed to the high QOL in this group of retired cricketers. CONCLUSIONS:
      Most retired cricketers in this study were living with pain or joint
      difficulties. Despite this, all but one was satisfied or very satisfied with
      their QOL. This may be partly explained by the positive psychological attributes
      that these retired cricketers shared.

PMID- 28751490
TI  - Panel OKs CAR T Therapy for Leukemia.
AB  - An expert panel recommended approval of Novartis's experimental chimeric antigen
      T-cell therapy, tisagenlecleucel, for children and young adults with relapsed or
      refractory B-cell acute lymphoblastic leukemia. The therapy would be the first of
      its kind approved for cancer and has the potential to transform standard of care
      for advanced blood cancers.

PMID- 28751491
TI  - Pediatric Chronic Critical Illness: Reducing Excess Hospitalizations.
AB  - OBJECTIVES: The past 2 decades have seen an expanding pediatric population that
      is chronically critically ill: children with repeated and prolonged
      hospitalizations and ongoing dependence on technologies to sustain vital
      functions. Although illness complexity prompts many hospitalizations, our goal
      with this study was to explore modifiable patient, family, and health system
      contributions to excess hospital days for children with chronic critical illness
      (CCI). METHODS: Semistructured interviews were conducted with 51 stakeholders
      known for their CCI expertise. Stakeholders were from 5 metropolitan areas and
      were either (1) interdisciplinary providers (inpatient and/or outpatient
      clinicians, home health providers, foster care affiliates, or policy
      professionals) or (2) parents of children with CCI. Interview transcripts were
      qualitatively analyzed for themes. RESULTS: All stakeholders agreed that homelike
      settings are ideal care sites for children with CCI, yet in every region these
      children experience prolonged hospitalizations. The perceived causes of excess
      hospital days are (1) inadequate communication and coordination within health
      care teams and between clinicians and families, (2) widespread gaps in qualified
      pediatric home health services and durable medical equipment providers, (3)
      inconsistent parent support, and (4) policies that limit pediatric service
      eligibility, state-supported case management, and nonhospital care sites.
      CONCLUSIONS: Despite an expanding pediatric population with CCI, we lack an
      intentional care model to minimize their hospitalizations. In this study, we
      generate several hypotheses for exploring the potential impact of expanded access
      to home nursing, robust care coordination, and family and clinician support to
      reduce hospital days for this population of high health care utilizers.

PMID- 28751492
TI  - Honeybees in a virtual reality environment learn unique combinations of colour
      and shape.
AB  - Honeybees are well-known models for the study of visual learning and memory.
      Whereas most of our knowledge of learned responses comes from experiments using
      free-flying bees, a tethered preparation would allow fine-scale control of the
      visual stimuli as well as accurate characterization of the learned responses.
      Unfortunately, conditioning procedures using visual stimuli in tethered bees have
      been limited in their efficacy. In this study, using a novel virtual reality
      environment and a differential training protocol in tethered walking bees, we
      show that the majority of honeybees learn visual stimuli, and need only six
      paired training trials to learn the stimulus. We found that bees readily learn
      visual stimuli that differ in both shape and colour. However, bees learn certain
      components over others (colour versus shape), and visual stimuli are learned in a
      non-additive manner with the interaction of specific colour and shape
      combinations being crucial for learned responses. To better understand which
      components of the visual stimuli the bees learned, the shape-colour association
      of the stimuli was reversed either during or after training. Results showed that
      maintaining the visual stimuli in training and testing phases was necessary to
      elicit visual learning, suggesting that bees learn multiple components of the
      visual stimuli. Together, our results demonstrate a protocol for visual learning
      in restrained bees that provides a powerful tool for understanding how components
      of a visual stimulus elicit learned responses as well as elucidating how visual
      information is processed in the honeybee brain.

PMID- 28751493
TI  - The nervous system does not compensate for an acute change in the balance of
      passive force between synergist muscles.
AB  - It is unclear how muscle activation strategies adapt to differential acute
      changes in the biomechanical characteristics between synergist muscles. This
      issue is fundamental to understanding the control of almost every joint in the
      body. The aim of this human experiment was to determine whether the relative
      activation of the heads of the triceps surae [gastrocnemius medialis (GM),
      gastrocnemius lateralis (GL) and soleus (SOL)] compensates for differential
      changes in passive force between these muscles. Twenty-four participants
      performed isometric ankle plantarflexion at 20 N m and 20% of the active torque
      measured during a maximal contraction, at three ankle angles (30 deg of
      plantarflexion, 0 and 25 deg of dorsiflexion; knee fully extended). Myoelectric
      activity (electromyography, EMG) provided an index of neural drive. Muscle shear
      modulus (elastography) provided an index of muscle force. Passive dorsiflexion
      induced a much larger increase in passive shear modulus for GM (+657.6+/-257.7%)
      than for GL (+488.7+/-257.9%) and SOL (+106.6+/-93.0%). However, the neural drive
      during submaximal tasks did not compensate for this change in the balance of the
      passive force. Instead, when considering the contraction at 20% MVC, GL root mean
      square (RMS) EMG was reduced at both 0 deg (-39.4+/-34.5%) and 25 deg
      dorsiflexion (-20.6+/-58.6%) compared with 30 deg plantarflexion, while GM and
      SOL RMS EMG did not change. As a result, the GM/GL ratio of shear modulus was
      higher at 0 deg and 25 deg dorsiflexion than at 30 deg plantarflexion, indicating
      that the greater the dorsiflexion angle, the stronger the bias of force to GM
      compared with GL. The magnitude of this change in force balance varied greatly
      between participants.

PMID- 28751494
TI  - Norway ranks first on supporting elderly people, UK 11th.

PMID- 28751495
TI  - Investigating palpitations: the role of Holter monitoring and loop recorders.

PMID- 28751496
TI  - Nup153 and Nup50 promote recruitment of 53BP1 to DNA repair foci by antagonizing
      BRCA1-dependent events.
AB  - DNA double-strand breaks are typically repaired through either the high-fidelity
      process of homologous recombination (HR), in which BRCA1 plays a key role, or the
      more error-prone process of non-homologous end joining (NHEJ), which relies on
      53BP1. The balance between NHEJ and HR depends, in part, on whether 53BP1
      predominates in binding to damage sites, where it protects the DNA ends from
      resection. The nucleoporin Nup153 has been implicated in the DNA damage response,
      attributed to a role in promoting nuclear import of 53BP1. Here, we define a
      distinct requirement for Nup153 in 53BP1 intranuclear targeting to damage foci
      and report that Nup153 likely facilitates the role of another nucleoporin, Nup50,
      in 53BP1 targeting. The requirement for Nup153 and Nup50 in promoting 53BP1
      recruitment to damage foci induced by either etoposide or olaparib is abrogated
      in cells deficient for BRCA1 or its partner BARD1, but not in cells deficient for
      BRCA2. Together, our results further highlight the antagonistic relationship
      between 53BP1 and BRCA1, and place Nup153 and Nup50 in a molecular pathway that
      regulates 53BP1 function by counteracting BRCA1-mediated events.

PMID- 28751497
TI  - The Cdk5-Mcl-1 axis promotes mitochondrial dysfunction and neurodegeneration in a
      model of Alzheimer's disease.
AB  - Cdk5 deregulation is highly neurotoxic in Alzheimer's disease (AD). We identified
      Mcl-1 as a direct Cdk5 substrate using an innovative chemical screen in mouse
      brain lysates. Our data demonstrate that Mcl-1 levels determine the threshold for
      cellular damage in response to neurotoxic insults. Mcl-1 is a disease-specific
      target of Cdk5, which associates with Cdk5 under basal conditions, but is not
      regulated by it. Neurotoxic insults hyperactivate Cdk5 causing Mcl-1
      phosphorylation at T92. This phosphorylation event triggers Mcl-1 ubiquitylation,
      which directly correlates with mitochondrial dysfunction. Consequently, ectopic
      expression of phosphorylation-dead T92A-Mcl-1 fully prevents mitochondrial damage
      and subsequent cell death triggered by neurotoxic treatments in neuronal cells
      and primary cortical neurons. Notably, enhancing Mcl-1 levels offers comparable
      neuroprotection to that observed upon Cdk5 depletion, suggesting that Mcl-1
      degradation by direct phosphorylation is a key mechanism by which Cdk5 promotes
      neurotoxicity in AD. The clinical significance of the Mcl-1-Cdk5 axis was
      investigated in human AD clinical specimens, revealing an inverse correlation
      between Mcl-1 levels and disease severity. These results emphasize the potential
      of Mcl-1 upregulation as an attractive therapeutic strategy for delaying or
      preventing neurodegeneration in AD.

PMID- 28751498
TI  - The cell polarity proteins Boi1p and Boi2p stimulate vesicle fusion at the plasma
      membrane of yeast cells.
AB  - Eukaryotic cells can direct secretion to defined regions of their plasma
      membrane. These regions are distinguished by an elaborate architecture of
      proteins and lipids that are specialized to capture and fuse post-Golgi vesicles.
      Here, we show that the proteins Boi1p and Boi2p are important elements of this
      area of active exocytosis at the tip of growing yeast cells. Cells lacking Boi1p
      and Boi2p accumulate secretory vesicles in their buds. The essential PH domains
      of Boi1p and Boi2p interact with Sec1p, a protein required for SNARE complex
      formation and vesicle fusion. Sec1p loses its tip localization in cells depleted
      of Boi1p and Boi2p but overexpression of Sec1p can partially compensate for their
      loss. The capacity to simultaneously bind phospholipids, Sec1p, multiple subunits
      of the exocyst, Cdc42p and the module for generating active Cdc42p identify Boi1p
      and Boi2p as essential mediators between exocytosis and polar growth.

PMID- 28751499
TI  - The initiator caspase Dronc plays a non-apoptotic role in promoting DNA damage
      signalling in D. melanogaster.
AB  - The phosphorylation of the variant histone H2Ax (denoted gammaH2Ax; gammaH2Av in
      flies) constitutes an important signalling event in DNA damage sensing, ensuring
      effective repair by recruiting DNA repair machinery. In contrast, the gammaH2Av
      response has also been reported in dying cells, where it requires activation of
      caspase-activated DNases (CADs). Moreover, caspases are known to be required
      downstream of DNA damage for cell death execution. We show here, for the first
      time, that the Drosophila initiator caspase Dronc acts as an upstream regulator
      of the DNA damage response (DDR) independently of executioner caspases by
      facilitating gammaH2Av signalling, possibly through a function that is not
      related to apoptosis. Such a gammaH2Av response is mediated by ATM rather than
      ATR, suggesting that Dronc function is required upstream of ATM. In contrast, the
      role of gammaH2Av in cell death requires effector caspases and is associated with
      fragmented nuclei. Our study uncovers a novel function of Dronc in response to
      DNA damage aimed at promoting DDR via gammaH2Av signalling in intact nuclei. We
      propose that Dronc plays a dual role that can either initiate DDR or apoptosis
      depending upon its level and the required threshold of its activation in damaged
      cells.This article has an associated First Person interview with the first author
      of the paper.

PMID- 28751500
TI  - Genome-Wide SNP Discovery and Analysis of Genetic Diversity in Farmed Sika Deer
      (Cervus nippon) in Northeast China Using Double-Digest Restriction Site
      Associated DNA Sequencing.
AB  - Sika deer are an economically valuable species owing to their use in traditional
      Chinese medicine, particularly their velvet antlers. Sika deer in northeast China
      are mostly farmed in enclosure. Therefore, genetic management of farmed sika deer
      would benefit from detailed knowledge of their genetic diversity. In this study,
      we generated over 1.45 billion high-quality paired-end reads (288 Gbp) across 42
      unrelated individuals using double-digest restriction site-associated DNA
      sequencing (ddRAD-seq). A total of 96,188 (29.63%) putative biallelic SNP loci
      were identified with an average sequencing depth of 23*. Based on the analysis,
      we found that the majority of the loci had a deficit of heterozygotes (FIS >0)
      and low values of Hobs, which could be due to inbreeding and Wahlund effects. We
      also developed a collection of high-quality SNP probes that will likely be useful
      in a variety of applications in genotyping for cervid species in the future.

PMID- 28751501
TI  - Ras/MAPK Modifier Loci Revealed by eQTL in Caenorhabditis elegans.
AB  - The oncogenic Ras/MAPK pathway is evolutionarily conserved across metazoans. Yet,
      almost all our knowledge on this pathway comes from studies using single genetic
      backgrounds, whereas mutational effects can be highly background dependent.
      Therefore, we lack insight in the interplay between genetic backgrounds and the
      Ras/MAPK-signaling pathway. Here, we used a Caenorhabditis elegans RIL population
      containing a gain-of-function mutation in the Ras/MAPK-pathway gene let-60 and
      measured how gene expression regulation is affected by this mutation. We mapped
      eQTL and found that the majority (~73%) of the 1516 detected cis-eQTL were not
      specific for the let-60 mutation, whereas most (~76%) of the 898 detected trans
      eQTL were associated with the let-60 mutation. We detected six eQTL trans-bands
      specific for the interaction between the genetic background and the mutation, one
      of which colocalized with the polymorphic Ras/MAPK modifier amx-2 Comparison
      between transgenic lines expressing allelic variants of amx-2 showed the
      involvement of amx-2 in 79% of the trans-eQTL for genes mapping to this trans
      band. Together, our results have revealed hidden loci affecting Ras/MAPK
      signaling using sensitized backgrounds in C. elegans These loci harbor putative
      polymorphic modifier genes that would not have been detected using mutant screens
      in single genetic backgrounds.

PMID- 28751502
TI  - The Douglas-Fir Genome Sequence Reveals Specialization of the Photosynthetic
      Apparatus in Pinaceae.
AB  - A reference genome sequence for Pseudotsuga menziesii var. menziesii (Mirb.)
      Franco (Coastal Douglas-fir) is reported, thus providing a reference sequence for
      a third genus of the family Pinaceae. The contiguity and quality of the genome
      assembly far exceeds that of other conifer reference genome sequences (contig N50
      = 44,136 bp and scaffold N50 = 340,704 bp). Incremental improvements in
      sequencing and assembly technologies are in part responsible for the higher
      quality reference genome, but it may also be due to a slightly lower exact repeat
      content in Douglas-fir vs. pine and spruce. Comparative genome annotation with
      angiosperm species reveals gene-family expansion and contraction in Douglas-fir
      and other conifers which may account for some of the major morphological and
      physiological differences between the two major plant groups. Notable differences
      in the size of the NDH-complex gene family and genes underlying the functional
      basis of shade tolerance/intolerance were observed. This reference genome
      sequence not only provides an important resource for Douglas-fir breeders and
      geneticists but also sheds additional light on the evolutionary processes that
      have led to the divergence of modern angiosperms from the more ancient
      gymnosperms.

PMID- 28751503
TI  - Ankyrin-1 Gene Exhibits Allelic Heterogeneity in Conferring Protection Against
      Malaria.
AB  - Allelic heterogeneity is a common phenomenon where a gene exhibits a different
      phenotype depending on the nature of its genetic mutations. In the context of
      genes affecting malaria susceptibility, it allowed us to explore and understand
      the intricate host-parasite interactions during malaria infections. In this
      study, we described a gene encoding erythrocytic ankyrin-1 (Ank-1) which exhibits
      allelic-dependent heterogeneous phenotypes during malaria infections. We
      conducted an ENU mutagenesis screen on mice and identified two Ank-1 mutations,
      one resulting in an amino acid substitution (MRI95845), and the other a truncated
      Ank-1 protein (MRI96570). Both mutations caused hereditary spherocytosis-like
      phenotypes and confer differing protection against Plasmodium chabaudi
      infections. Upon further examination, the Ank-1(MRI96570) mutation was found to
      inhibit intraerythrocytic parasite maturation, whereas Ank-1(MRI95845) caused
      increased bystander erythrocyte clearance during infection. This is the first
      description of allelic heterogeneity in ankyrin-1 from the direct comparison
      between two Ank-1 mutations. Despite the lack of direct evidence from population
      studies, this data further supported the protective roles of ankyrin-1 mutations
      in conferring malaria protection. This study also emphasized the importance of
      such phenomena in achieving a better understanding of host-parasite interactions,
      which could be the basis of future studies.

PMID- 28751504
TI  - The Caenorhabditis elegans Female-Like State: Decoupling the Transcriptomic
      Effects of Aging and Sperm Status.
AB  - Understanding genome and gene function in a whole organism requires us to fully
      comprehend the life cycle and the physiology of the organism in question.
      Caenorhabditis elegans XX animals are hermaphrodites that exhaust their sperm
      after 3 d of egg-laying. Even though C. elegans can live for many days after
      cessation of egg-laying, the molecular physiology of this state has not been as
      intensely studied as other parts of the life cycle, despite documented changes in
      behavior and metabolism. To study the effects of sperm depletion and aging of C.
      elegans during the first 6 d of adulthood, we measured the transcriptomes of
      first-day adult hermaphrodites and sixth-day sperm-depleted adults, and, at the
      same time points, mutant fog-2(lf) worms that have a feminized germline
      phenotype. We found that we could separate the effects of biological aging from
      sperm depletion. For a large subset of genes, young adult fog-2(lf) animals had
      the same gene expression changes as sperm-depleted sixth-day wild-type
      hermaphrodites, and these genes did not change expression when fog-2(lf) females
      reached the sixth day of adulthood. Taken together, this indicates that changing
      sperm status causes a change in the internal state of the worm, which we call the
      female-like state. Our data provide a high-quality picture of the changes that
      happen in global gene expression throughout the period of early aging in the
      worm.

PMID- 28751506
TI  - Junior doctors can use the new contract to take back some control.

PMID- 28751505
TI  - The Integrated Genomic Architecture and Evolution of Dental Divergence in East
      African Cichlid Fishes (Haplochromis chilotes x H. nyererei).
AB  - The independent evolution of the two toothed jaws of cichlid fishes is thought to
      have promoted their unparalleled ecological divergence and species richness.
      However, dental divergence in cichlids could exhibit substantial genetic
      covariance and this could dictate how traits like tooth numbers evolve in
      different African Lakes and on their two jaws. To test this hypothesis, we used a
      hybrid mapping cross of two trophically divergent Lake Victoria species
      (Haplochromis chilotes * Haplochromis nyererei) to examine genomic regions
      associated with cichlid tooth diversity. Surprisingly, a similar genomic region
      was found to be associated with oral jaw tooth numbers in cichlids from both Lake
      Malawi and Lake Victoria. Likewise, this same genomic location was associated
      with variation in pharyngeal jaw tooth numbers. Similar relationships between
      tooth numbers on the two jaws in both our Victoria hybrid population and across
      the phylogenetic diversity of Malawi cichlids additionally suggests that tooth
      numbers on the two jaws of haplochromine cichlids might generally coevolve owing
      to shared genetic underpinnings. Integrated, rather than independent, genomic
      architectures could be key to the incomparable evolutionary divergence and
      convergence in cichlid tooth numbers.

PMID- 28751507
TI  - Commentary on "Weekly Low-Dose Versus Three-Weekly High-Dose Cisplatin for
      Concurrent Chemoradiation in Locoregionally Advanced Non-Nasopharyngeal Head and
      Neck Cancer: A Systematic Review and Meta-Analysis of Aggregate Data".

PMID- 28751509
TI  - Giant oesophageal gastrointestinal stromal tumour presenting with dyspnoea and
      clubbed fingers.
AB  - Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms of the
      gastrointestinal tract originating from the interstitial cells of Cajal. Giant
      oesophageal GISTs are rare since the oesophagus is rarely the primary site of
      GISTs, and they are usually diagnosed early due to complaints such as dysphagia.
      We present the case of a giant oesophageal GIST presenting with prominent
      clubbing. The case underlined the diagnostic importance of clubbing and the
      careful consideration of chemotherapy. Although clubbed fingers associated with
      GISTs are rare, our experience demonstrates the importance of physicians'
      recognition of clubbing as a paraneoplastic phenomenon for early diagnosis of
      malignancies since patients seldom notice their own clubbing by themselves.
      Chemotherapy using imatinib, an Bcr-Abl kinase inhibitor, is the standard option
      for unresectable giant GISTs. However, careful consideration must be made of the
      risk of complications associated with rapid mass reduction due to imatinib such
      as bleeding, oesophageal perforation and mediastinitis.

PMID- 28751508
TI  - Between fire and ice: refractory hypothermia and warmth-induced pain in inherited
      erythromelalgia.
AB  - Inherited erythromelalgia (IEM) is a well-described pain disorder caused by
      mutations of sodium channel Nav1.7, a peripheral channel expressed within dorsal
      root ganglion and the sympathetic ganglion neurons. Clinically, IEM is
      characterised by paroxysmal attacks of severe pain, usually in the distal
      extremities, triggered by warmth or exercise. Pain is not adequately treated by
      existing pharmacological agents. Individuals with IEM classically cool their
      limbs for relief, in some cases resulting in tissue injury. We describe a patient
      from a family with IEM due to the L858F mutation of Nav1.7 who presented with
      refractory hypothermia due to overcooling. This presentation of refractory
      hypothermia necessitating warming strategies, complicated by severe warmth
      induced pain, posed a substantial therapeutic challenge. We report our experience
      in overcoming hypothermia lasting 3 weeks in a child with IEM, discuss possible
      pathophysiological mechanisms underlying this unusual complication and suggest
      potential therapeutic interventions.

PMID- 28751510
TI  - Optimising the surgical outcome in a case of post-traumatic cataract using
      ultrasound biomicroscopy.
AB  - A 12-year-old boy was brought with the chief complaint of diminution of vision in
      his left eye for the past 1 month. History revealed a blunt trauma to his left
      eye with a wooden stick 6a?0/00weeks ago.Visual acuity was 20/20 and hand
      movement close to face in right and left eye, respectively, without any relative
      afferent pupillarydefect. Slit-lamp examination showed a total cataractous lens
      with signs suggestive of suspected posterior capsular (PC) defect. The PC defect
      was screened initially using B-scan ultrasound of the posterior segment, followed
      by confirmation of the same using ultrasound biomicroscopy. Left eye lens
      aspiration along with limited anterior vitrectomy followed by placement of
      multipiece intraocular lens in the sulcus was performed. Best-corrected visual
      acuity at 6 months of follow-up was 20/20.

PMID- 28751511
TI  - Type I talon cusp on mandibular incisor.

PMID- 28751512
TI  - Flat Panel Angiography in the Cross-Sectional Imaging of the Temporal Bone:
      Assessment of Image Quality and Radiation Dose Compared with a 64-Section
      Multisection CT Scanner.
AB  - BACKGROUND AND PURPOSE: Cross-sectional imaging of the temporal bone is
      challenging because of the complexity and small dimensions of the anatomic
      structures. We evaluated the role of flat panel angiography in the cross
      sectional imaging of the temporal bone by comparing its image quality and
      radiation dose with a 64-section multisection CT scanner. MATERIALS AND METHODS:
      We retrospectively collected 29 multisection CT and 29 flat panel angiography
      images of normal whole-head temporal bones. Image quality was assessed by 2
      neuroradiologists, who rated the visualization of 30 anatomic structures with a 3
      point ordinal scale. The radiation dose was assessed with an anthropomorphic
      phantom. RESULTS: Flat panel angiography showed better image quality than
      multisection CT in depicting the anterior and posterior crura of the stapes, the
      footplate of the stapes, the stapedius muscle, and the anterior ligament of the
      malleus (P < .05). In contrast, multisection CT showed better image quality than
      flat panel angiography in assessing the tympanic membrane, the bone marrow of the
      malleus and incus, the tendon of the tensor tympani, the interscalar septum, and
      the modiolus of the cochlea (P < .05). Flat panel angiography had a significantly
      higher overall image quality rating than multisection CT (P = .035). A reduction
      of the effective dose of approximately 40% was demonstrated for flat panel
      angiography compared with multisection CT. CONCLUSIONS: Flat panel angiography
      shows strengths and weaknesses compared with multisection CT. It is more
      susceptible to artifacts, but due to the higher spatial resolution, it shows
      equal or higher image quality in assessing some bony structures of diagnostic
      interest. The lower radiation dose is an additional advantage of flat panel
      angiography.

PMID- 28751513
TI  - Zika Virus Iceberg: Very Large.

PMID- 28751514
TI  - Syringomyelia Fluid Dynamics and Cord Motion Revealed by Serendipitous Null Point
      Artifacts during Cine MRI.
AB  - Dynamic MR imaging was used to evaluate a cervical syrinx in an adolescent boy
      with an associated hindbrain herniation. Null artifacts were present on one of
      the sequences that allowed simultaneous high-resolution visualization of syrinx
      fluid motion and the anatomy of the syrinx walls. A brief review of the theories
      of syrinx formation and propagation is provided with a comment on why the
      Williams "slosh" theory of syrinx progression is supported by our unique imaging.

PMID- 28751515
TI  - Concordance of Time-of-Flight MRA and Digital Subtraction Angiography in Adult
      Primary Central Nervous System Vasculitis.
AB  - BACKGROUND AND PURPOSE: 3D-TOF-MRA and DSA are 2 available tools to demonstrate
      neurovascular involvement in primary central nervous system vasculitis. We aimed
      to compare the diagnostic concordance of vessel imaging using 3D-TOF-MRA and DSA
      in patients with primary central nervous system vasculitis. MATERIALS AND
      METHODS: We retrospectively identified all patients included in the French
      primary central nervous system vasculitis cohort of 85 patients who underwent, at
      baseline, both intracranial 3D-TOF-MRA and DSA in an interval of no more than 2
      weeks and before treatment initiation. Two neuroradiologists independently
      reviewed all 3D-TOF-MRA and DSA imaging. Brain vasculature was divided into 25
      arterial segments. Concordance between 3D-TOF-MRA and DSA for the identification
      of arterial stenosis was assessed by the Cohen kappa Index. RESULTS: Thirty-one
      patients met the inclusion criteria, including 20 imaged with a 1.5T MR unit and
      11 with a 3T MR unit. Among the 25 patients (81%) with abnormal DSA findings, 24
      demonstrated abnormal 3D-TOF-MRA findings, whereas all 6 remaining patients with
      normal DSA findings had normal 3D-TOF-MRA findings. In the per-segment analysis,
      concordance between 1.5T 3D-TOF-MRA and DSA was 0.82 (95% CI, 0.75-0.93), and
      between 3T 3D-TOF-MRA and DSA, it was 0.87 (95% CI, 0.78-0.91). CONCLUSIONS: 3D
      TOF-MRA shows a high concordance with DSA in diagnostic performance when
      analyzing brain vasculature in patients with primary central nervous system
      vasculitis. In patients with negative 3T 3D-TOF-MRA findings, the added
      diagnostic value of DSA is limited.

PMID- 28751516
TI  - The Use and Utility of Aspiration Thrombectomy in Acute Ischemic Stroke: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Thrombectomy trials are often specifically interpreted as evidence
      for the effectiveness of stent retrievers. The effectiveness of other
      thrombectomy techniques such as aspiration thrombectomy should be validated
      through further investigation and review. PURPOSE: To evaluate published
      treatment times and clinical outcomes in patients treated with aspiration
      thrombectomy or ADAPT (A Direct Aspiration, First Pass Technique) for acute
      ischemic stroke. DATA SOURCES: A systematic literature review was performed
      following Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) guidelines. MEDLINE, Scopus, and the Cochrane trial register were
      searched on November 8, 2016. STUDY SELECTION: Twenty studies (n = 1523 patients)
      were included in this review and meta-analysis. One of these studies was
      prospective, and the rest were retrospective. DATA ANALYSIS: Meta-analysis was
      performed by using a random effects model. Data and publication bias were
      visualized with forest plots and funnel plots. DATA SYNTHESIS: Five studies
      investigated aspiration thrombectomy only, and 16 studies investigated ADAPT. Of
      the 16 studies on ADAPT, the rate of successful recanalization (TICI 2b/3) was
      89.3% (95% CI, 85.4%-92.3%). The proportion of patients with good clinical
      outcome (90-day mRS <=2) was 52.7% (95% CI, 48.0%-57.4%). LIMITATIONS: Studies on
      ADAPT were retrospective, and there was heterogeneity between studies for
      successful recanalization (P < .001) and good clinical outcome (P < .001). There
      was evidence of publication bias for recanalization rates (P = .01), but not for
      clinical outcomes (P = .42). CONCLUSIONS: ADAPT and aspiration thrombectomy are
      effective approaches to thrombectomy, with high recanalization rates and
      excellent clinical outcomes reported in the literature. Aspiration thrombectomy
      is a promising neurointervention, but large prospective randomized studies are
      needed to validate its utility.

PMID- 28751517
TI  - Packing Density Necessary to Reach a High Complete Occlusion Rate in
      Circumferential Unruptured Intracranial Aneurysms Treated with Stent-Assisted
      Coil Embolization.
AB  - BACKGROUND AND PURPOSE: This study is a homogeneous series of circumferential
      unruptured intracranial aneurysms with large necks treated with stent-assisted
      coil embolization. Our purpose was to demonstrate which value of packing density
      is required to produce a durable occlusion. MATERIALS AND METHODS: We
      retrospectively evaluated all patients with unruptured intracranial aneurysms who
      were treated with stent-assisted coil embolization having late angiographic
      control between 2004 and 2014, in a single large cerebrovascular referral center.
      To calculate the packing density, aneurysm volume, and coil volume, we used an on
      line system. RESULTS: In 49 circumferential unruptured intracranial aneurysms
      treated with stent-assisted coil embolization, 38.7% (n = 19) had complete
      occlusion in the immediate control. Of those with incomplete occlusion, 80% (n =
      24) progressed to complete occlusion in the late angiographic follow-up. At late
      angiographic control, 87.7% (n = 43) of aneurysms were completely occluded. All
      aneurysms with a packing density of >=19% were completely occluded. Packing
      density was the only statistically significant predictor of complete occlusion.
      None of the aneurysms with complete occlusion at immediate control or at late
      angiographic control had recurrence. CONCLUSIONS: In circumferential aneurysms
      treated with stent-assisted coil embolization, packing density is the main
      predictor of complete occlusion. In this type of aneurysm, a packing density of
      >=19% was enough to reach complete occlusion; knowing this is important to avoid
      higher packing densities that have more risk.

PMID- 28751518
TI  - Pre- and Postcontrast 3D Double Inversion Recovery Sequence in Multiple
      Sclerosis: A Simple and Effective MR Imaging Protocol.
AB  - BACKGROUND AND PURPOSE: The double inversion recovery sequence is known to be
      very sensitive and specific for MS-related lesions. Our aim was to compare the
      sensitivity of pre- and postcontrast images of 3D double inversion recovery and
      conventional 3D T1-weighted images for the detection of contrast-enhancing MS
      related lesions in the brain to analyze whether double inversion recovery could
      be as effective as T1WI. MATERIALS AND METHODS: A postcontrast 3D double
      inversion recovery sequence was acquired in addition to the standard MR imaging
      protocol at 3T, including pre- and postcontrast 3D T1WI sequences as well as
      precontrast double inversion recovery of 45 consecutive patients with MS or
      clinically isolated syndrome between June and December 2013. Two
      neuroradiologists independently assessed precontrast, postcontrast, and
      subtraction images of double inversion recovery as well as T1WI to count the
      number of contrast-enhancing lesions. Afterward, a consensus reading was
      performed. Lin concordance was calculated between both radiologists, and
      differences in lesion detectability were assessed with the Student t test.
      Additionally, the contrast-to-noise ratio was calculated. RESULTS: Significantly
      more contrast-enhancing lesions could be detected with double inversion recovery
      compared with T1WI (16%, 214 versus 185, P = .007). The concordance between both
      radiologists was almost perfect (rhoc = 0.94 for T1WI and rhoc = 0.98 for double
      inversion recovery, respectively). The contrast-to-noise ratio was significantly
      higher in double inversion recovery subtraction images compared with T1-weighted
      subtraction images (double inversion recovery, 14.3 +/- 5.5; T1WI, 6.3 +/- 7.1; P
      < .001). CONCLUSIONS: Pre- and postcontrast double inversion recovery enables
      better detection of contrast-enhancing lesions in MS in the brain compared with
      T1WI and may be considered an alternative to the standard MR imaging protocol.

PMID- 28751519
TI  - Value of Thrombus CT Characteristics in Patients with Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Thrombus CT characteristics might be useful for patient
      selection for intra-arterial treatment. Our objective was to study the
      association of thrombus CT characteristics with outcome and treatment effect in
      patients with acute ischemic stroke. MATERIALS AND METHODS: We included 199
      patients for whom thin-section NCCT and CTA within 30 minutes from each other
      were available in the Multicenter Randomized Clinical Trial of Endovascular
      Treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) study. We
      assessed the following thrombus characteristics: location, distance from ICA
      terminus to thrombus, length, volume, absolute and relative density on NCCT, and
      perviousness. Associations of thrombus characteristics with outcome were
      estimated with univariable and multivariable ordinal logistic regression as an OR
      for a shift toward better outcome on the mRS. Interaction terms were used to
      investigate treatment-effect modification by thrombus characteristics. RESULTS:
      In univariate analysis, only the distance from the ICA terminus to the thrombus,
      length of >8 mm, and perviousness were associated with functional outcome.
      Relative thrombus density on CTA was independently associated with functional
      outcome with an adjusted common OR of 1.21 per 10% (95% CI, 1.02-1.43; P = .029).
      There was no treatment-effect modification by any of the thrombus CT
      characteristics. CONCLUSIONS: In our study on patients with large-vessel
      occlusion of the anterior circulation, CT thrombus characteristics appear useful
      for predicting functional outcome. However, in our study cohort, the effect of
      intra-arterial treatment was independent of the thrombus CT characteristics.
      Therefore, no arguments were provided to select patients for intra-arterial
      treatment using thrombus CT characteristics.

PMID- 28751520
TI  - Validation of the Singapore nomogram for outcome prediction in breast phyllodes
      tumours in a large patient cohort.
AB  - AIMS: To validate the Singapore nomogram for outcome prediction in breast
      phyllodes tumours in a large cohort of Singaporean patients, as previous
      validation studies were conducted on small numbers of patients. We also
      investigate the association of fibroadenomas and phyllodes tumours within a
      subset of our cohort. METHODS: Histological parameters, surgical margin status
      and clinical follow-up data of 259 women diagnosed with phyllodes tumours were
      analysed. Patients with concurrent malignant or premalignant disease were
      excluded from the validation to minimise confounding influences. Biostatistics
      modelling was performed, and the concordance between predicted and observed
      survivals was calculated. The association between fibroadenomas and phyllodes
      tumours was quantified in a subset of the women. RESULTS: Phyllodes tumours with
      higher number of mitoses, stromal overgrowth and positive surgical margins were
      found to be associated with greater risk of clinical recurrence. Patients with a
      higher nomogram score had a significantly higher risk of developing relapse.
      Forty out of 78 (51.3%) of the subset of phyllodes cases reviewed showed either
      fibroadenoma-like areas within the phyllodes tumours or concurrent fibroadenomas
      in the ipsilateral or contralateral breast. CONCLUSIONS: The Singapore nomogram
      is useful in predicting outcome in breast phyllodes tumours when applied to a
      large cohort of Singaporean women.

PMID- 28751521
TI  - The third pathway of colorectal carcinogenesis.
AB  - AIMS: The majority of the colorectal carcinomas (CRC) arise in a vast mucosal
      area built with columnar cells and mucus-producing goblet cells. These carcinomas
      evolve via the conventional (tubular/villous) adenoma-carcinoma pathway, or the
      serrated adenoma-carcinoma pathway. Much less frequently CRC arise in the gut
      associated lymphoid tissue (GALT) mucosal domain via the third pathway of
      colorectal carcinogenesis. METHODS: All publications on human colorectal GALT
      carcinomas in the literature were reviewed. RESULTS: Only 23 GALT-carcinomas
      found in 20 patients are in record. The GALT carcinomas were detected at
      surveillance colonoscopic biopsy in 11 patients (four had ulcerative colitis, two
      were members of a Lynch syndrome family, two of a CRC family, one had familial
      adenomatous polyposis (FAP), one prior colon adenomas and one a submucosal
      tumour), or at diagnostic colonoscopic biopsy in the remaining nine patients
      (three had rectal bleedings, two abdominal pains, one diverticular disease and
      one protracted constipation. In three, no ground disease or symptoms were
      provided). In six of the 23 GALT carcinomas, the luminal surface showed tumour
      cells, ulcerations or no descriptions were given. Ten (66.7%) of the remaining 15
      GALT carcinomas showed on top, adenomas (n=8) or high-grade dysplasia (n=2).
      CONCLUSIONS: The low frequency of GALT carcinomas might be explained by the fact
      that the colorectal mucosal areas occupied by GALT domains are minute. The
      finding that two-thirds of the 15 remaining GALT carcinomas (vide supra) were
      covered by high-grade dysplasia or by conventional adenomas strongly suggest that
      conventional non-invasive neoplasias might have preceded the majority of the GALT
      carcinomas in record.

PMID- 28751522
TI  - Liver allograft biopsies with histological cholestasis: a clinicopathological
      study of 254 cases from a single centre.
AB  - AIMS: Liver allograft biopsy is important in the management of liver transplant
      (LT) recipients. Cholestasis is an indicator of liver dysfunction, and
      histological evidence of cholestasis can be observed in a wide range of
      pathological entities in the post-LT setting. In this study, we describe the
      clinicopathological features and significance of liver allograft biopsies with
      histological cholestasis over 11 years in our centre. METHODS: Liver allograft
      biopsies performed in Queen Mary Hospital, Hong Kong from 2004 to 2014 showing
      histological cholestasis were retrieved from the pathology archive. Clinical and
      pathological data were retrospectively reviewed and analyzed. RESULTS: Among the
      254 biopsies from 167 patients, large duct obstruction (LDO) and acute cellular
      rejection (ACR) were the two main aetiologies associated with cholestasis. There
      was a decrease in sepsis as a cause over the study duration. In cases showing
      cholestasis at 6 months or more after LT, LDO was more common than ACR. Over half
      (61%) of the 254 biopsies showed mild cholestasis. Severe panacinar cholestasis
      was more often observed in LDO. Mild cholestasis was most commonly observed
      regardless of the severity of ACR. Severe cholestasis was associated with poorer
      1-year and 3-year graft survival and patient survival, as well as higher 3-month
      and 6-month post-biopsy mortality. CONCLUSION: Histological cholestasis and its
      severity in liver allograft biopsies has clinical and prognostic significance.
      Our study summarizes our previous experience and provides further insights into
      the management of post-LT patients.

PMID- 28751523
TI  - CCL3 is a key mediator for the leukemogenic effect of Ptpn11-activating mutations
      in the stem-cell microenvironment.

PMID- 28751525
TI  - PGC-1alpha Protects from Notch-Induced Kidney Fibrosis Development.
AB  - Kidney fibrosis is the histologic manifestation of CKD. Sustained activation of
      developmental pathways, such as Notch, in tubule epithelial cells has been shown
      to have a key role in fibrosis development. The molecular mechanism of Notch
      induced fibrosis, however, remains poorly understood. Here, we show that, that
      expression of peroxisomal proliferation g-coactivator (PGC-1alpha) and fatty acid
      oxidation-related genes are lower in mice expressing active Notch1 in tubular
      epithelial cells (Pax8-rtTA/ICN1) compared to littermate controls. Chromatin
      immunoprecipitation assays revealed that the Notch target gene Hes1 directly
      binds to the regulatory region of PGC-1alpha Compared with Pax8-rtTA/ICN1
      transgenic animals, Pax8-rtTA/ICN1/Ppargc1a transgenic mice showed improvement of
      renal structural alterations (on histology) and molecular defect (expression of
      profibrotic genes). Overexpression of PGC-1alpha restored mitochondrial content
      and reversed the fatty acid oxidation defect induced by Notch overexpression in
      vitro in tubule cells. Furthermore, compared with Pax8-rtTA/ICN1 mice, Pax8
      rtTA/ICN1/Ppargc1a mice exhibited improvement in renal fatty acid oxidation gene
      expression and apoptosis. Our results show that metabolic dysregulation has a key
      role in kidney fibrosis induced by sustained activation of the Notch
      developmental pathway and can be ameliorated by PGC-1alpha.

PMID- 28751524
TI  - MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging
      concepts.
AB  - Acute myeloid leukemia (AML) is a deadly hematologic malignancy characterized by
      the uncontrolled growth of immature myeloid cells. Over the past several decades,
      we have learned a tremendous amount regarding the genetic aberrations that govern
      disease development in AML. Among these are genes that encode noncoding RNAs,
      including the microRNA (miRNA) family. miRNAs are evolutionarily conserved small
      noncoding RNAs that display important physiological effects through their
      posttranscriptional regulation of messenger RNA targets. Over the past decade,
      studies have identified miRNAs as playing a role in nearly all aspects of AML
      disease development, including cellular proliferation, survival, and
      differentiation. These observations have led to the study of miRNAs as biomarkers
      of disease, and efforts to therapeutically manipulate miRNAs to improve disease
      outcome in AML are ongoing. Although much has been learned regarding the
      importance of miRNAs in AML disease initiation and progression, there are many
      unanswered questions and emerging facets of miRNA biology that add complexity to
      their roles in AML. Moving forward, answers to these questions will provide a
      greater level of understanding of miRNA biology and critical insights into the
      many translational applications for these small regulatory RNAs in AML.

PMID- 28751526
TI  - The salivary peptide histatin-1 promotes endothelial cell adhesion, migration,
      and angiogenesis.
AB  - Saliva is a key factor that contributes to the high efficiency of wound healing
      in the oral mucosa. This is not only attributed to physical cues but also to the
      presence of specific peptides in the saliva, such as histatins. Histatin-1 is a
      38 aa antimicrobial peptide, highly enriched in human saliva, which has been
      previously reported to promote the migration of oral keratinocytes and
      fibroblasts in vitro However, the participation of histatin-1 in other crucial
      events required for wound healing, such as angiogenesis, is unknown. Here we
      demonstrate that histatin-1 promotes angiogenesis, as shown in vivo, using the
      chick chorioallantoic membrane model, and by an in vitro tube formation assay,
      using both human primary cultured endothelial cells (HUVECs) and the EA.hy926
      cell line. Specifically, histatin-1 promoted endothelial cell adhesion and
      spreading onto fibronectin, as well as endothelial cell migration in the wound
      closure and Boyden chamber assays. These actions required the activation of the
      Ras and Rab interactor 2 (RIN2)/Rab5/Rac1 signaling axis, as histatin-1 increased
      the recruitment of RIN2, a Rab5-guanine nucleotide exchange factor (GEF) to early
      endosomes, leading to sequential Rab5/Rac1 activation. Accordingly, interfering
      with either Rab5 or Rac1 activities prevented histatin-1-dependent endothelial
      cell migration. Finally, by immunodepletion assays, we showed that salivary
      histatin-1 is required for the promigratory effects of saliva on endothelial
      cells. In conclusion, we report that salivary histatin-1 is a novel proangiogenic
      factor that may contribute to oral wound healing.-Torres, P., Diaz, J., Arce, M.,
      Silva, P., Mendoza, P., Lois, P., Molina-Berrios, A., Owen, G. I., Palma, V.,
      Torres, V. A. The salivary peptide histatin-1 promotes endothelial cell adhesion,
      migration, and angiogenesis.

PMID- 28751529
TI  - First discovery of the charophycean green alga Lychnothamnus barbatus
      (Charophyceae) extant in the New World.
AB  - PREMISE OF THE STUDY: Although some species of Characeae, known as stoneworts,
      can be found on every continent except Antarctica, many species and some genera
      have limited geographic distributions. The genus Lychnothamnus, represented by a
      single extant species L. barbatus, was known only from scattered localities in
      Europe and Australasia until it was recently discovered in North America.
      METHODS: Morphological identifications were made from specimens collected in
      Minnesota and Wisconsin, USA. DNA sequences were obtained for three plastid
      encoded genes (atpB, psbC, rbcL) from seven putative Lychnothamnus samples from
      two states in the USA Distribution and abundance were estimated in each lake
      using point intercept surveys where surveyors sampled aquatic vegetation. KEY
      RESULTS: Fourteen lakes in Wisconsin and two lakes in Minnesota, USA, were found
      to harbor Lychnothamnus barbatus. These represent the first report of this rare
      charophycean extant in the New World. The North American specimens matched the
      morphological description for L. barbatus and were compared directly with the
      neotype. Phylogenetic results using three plastid-encoded genes confirmed the
      identification placing New World samples with those from Europe and Australasia.
      Our phylogenetic analyses also confirmed the sister relationship between L.
      barbatus and Nitellopsis obtusa. CONCLUSIONS: Because this taxon is not known for
      aggressive invasiveness in its native range, it may have existed in heretofore
      undiscovered native populations, although the possibility that it is a recent
      introduction cannot be eliminated. The potential for discovery of novel lineages
      of green algae in even well-studied regions is apparently far from exhausted.

PMID- 28751530
TI  - A 10-year review of child injury hospitalisations, health outcomes and treatment
      costs in Australia.
AB  - BACKGROUND: Childhood injury is a leading cause of hospitalisation, yet there has
      been no comprehensive examination of child injury and survival over time in
      Australia. To examine the characteristics, temporal trend and survival for
      children who were hospitalised as a result of injury in Australia. METHOD: A
      retrospective examination of linked hospitalisation and mortality data for
      injured children aged 16 years or less during 1 July 2001 to 30 June 2012.
      Negative binomial regression examined change in injury hospitalisation trends.
      Cox proportional hazard regression examined the association of risk factors on 30
      day survival. RESULTS: There were 6 86 409 injury hospitalisations, with an age
      standardised rate of 1489 per 1 00 000 population (95% CI 1485.3 to 1492.4) in
      Australia. Child injury hospitalisation rates did not change over the 10-year
      period. For every severely injured child, there are at least 13 children
      hospitalised with minor or moderate injuries. The total cost of child injury
      hospitalisations was $A2.1 billion (annually $A212 million). Falls (38.4%) were
      the most common injury mechanism. Factors associated with a higher risk of 30-day
      mortality were: child was aged <=10 years, higher injury severity, head injury,
      injured in a transport incident or following drowning and submersion or other
      threats to breathing, during self-harm and usual residence was regional/remote
      Australia. CONCLUSIONS: Childhood injury hospitalisation rates have not reduced
      in 10 years. Children's patterns of injury change with age, and priorities for
      injury prevention alter according to developmental stages. The development of a
      national multisectorial childhood injury monitoring and prevention strategy in
      Australia is long overdue.

PMID- 28751527
TI  - In utero exposure to diesel exhaust particulates is associated with an altered
      cardiac transcriptional response to transverse aortic constriction and altered
      DNA methylation.
AB  - In utero exposure to diesel exhaust air pollution has been associated with
      increased adult susceptibility to heart failure in mice, but the mechanisms by
      which this exposure promotes susceptibility to heart failure are poorly
      understood. To identify the potential transcriptional effects that mediate this
      susceptibility, we have performed RNA sequencing analysis on adult hearts from
      mice that were exposed to diesel exhaust in utero and that have subsequently
      undergone transverse aortic constriction. We identified 3 target genes, Mir133a
      2, Ptprf, and Pamr1, which demonstrate dysregulation after exposure and aortic
      constriction. Examination of expression patterns in human heart tissues indicates
      a correlation between expression and heart failure. We subsequently assessed DNA
      methylation modifications at these candidate loci in neonatal cultured cardiac
      myocytes after in utero exposure to diesel exhaust and found that the promoter
      for Mir133a-2 is differentially methylated. These target genes in the heart are
      the first genes to be identified that likely play an important role in mediating
      adult sensitivity to heart failure. We have also shown a change in DNA
      methylation within cardiomyocytes as a result of in utero exposure to diesel
      exhaust.-Goodson, J. M., Weldy, C. S., MacDonald, J. W., Liu, Y., Bammler, T. K.,
      Chien, W.-M., Chin, M. T. In utero exposure to diesel exhaust particulates is
      associated with an altered cardiac transcriptional response to transverse aortic
      constriction and altered DNA methylation.

PMID- 28751531
TI  - The preventive effect of a soccer-specific ankle brace on acute lateral ankle
      sprains in girls amateur soccer players: study protocol of a cluster-randomised
      controlled trial.
AB  - BACKGROUND: Acute lateral ankle sprains are the single most often diagnosed
      injury in female soccer players and often result in an inability to play. This
      highlights the need for effective prevention strategies. Proprioceptive training
      and/or the use of an external support to decrease inversion of the ankle joint
      can prevent or reduce the number of acute lateral ankle sprains. The
      effectiveness of a soccer-specific ankle brace in reducing first-time and
      recurrent acute lateral ankle sprains has never been investigated in girl soccer
      players. If effective, ankle braces could be introduced into soccer. STUDY
      DESIGN: Cluster-randomised controlled trial. METHODS: Girl amateur soccer players
      (aged 14-18 years) will be allocated to an intervention or control group. The
      intervention group will be instructed to wear soccer-specific ankle braces on
      both ankles during soccer training and matches; the control group will continue
      playing soccer as usual. Primary outcomes are the incidence and severity of acute
      lateral ankle sprains. Secondary outcomes are the prognostic value of generalised
      joint hypermobility and functional stability on the risk of acute lateral ankle
      sprains and compliance with the intervention. DISCUSSION: The findings from this
      study may provide evidence to support the use of a soccer-specific ankle brace to
      prevent lateral ankle sprains during soccer. We hypothesise that this brace will
      reduce the incidence of ankle sprains among young amateur girl soccer players by
      50%. The prevention of such injuries will be beneficial to players, clubs and
      society. TRIAL REGISTRATION NUMBER: The Netherlands Trial Register (NTR):
      NTR6045; Pre-results.

PMID- 28751532
TI  - Attempted suicide among adolescents in Mexico: prevalence and associated factors
      at the national level.
AB  - OBJECTIVE: To determine the prevalence and associated factors of attempted
      suicide (AS) in a sample of Mexican adolescents between 10 and 19 years of age.
      METHODS: A cross-sectional study was conducted with data from the 2012 National
      Health and Nutrition Survey (ENSANUT 2012 by its initials in Spanish). Based on
      multi-stage stratified probability sampling, ENSANUT 2012 canvassed 50 528
      households including 21 519 adolescents. A logistic regression model was used to
      identify the factors associated with AS. The model was selected based on the
      maximum likelihood test. RESULTS: Lifetime prevalence of AS amounted to 2.7% and
      was heterogeneously distributed across Mexico. Women showed significantly higher
      risk for AS than men (ORA(adjusted OR)) 6.3, 95% confidence interval CI 4.94 to
      8.06), and individuals who experienced damage to health caused by violence over
      the last 12 months were 4.35 times (ORA 4.35, 95% CI 3.27 to 5.80) more likely to
      engage in AS than those who did not. The likelihood of engaging in AS was 1.5
      times higher (ORA1.5 (95% CI 1.12 to 2.01)) among subjects with mild and 4.22
      times higher (95% CI 3.21 to 5.54) among subjects with moderate eating disorders
      compared to those with no eating disorders. Other AS-associated factors included
      age, smoking, consuming alcohol and living with relatives other than parents.
      CONCLUSIONS: Awareness of the risk factors associated with AS can help identify
      the populations who are exposed to injury or death by suicide. This can orient
      the actions of the health sector towards those who are most vulnerable. Actions
      must be matched by more qualitative and quantitative research on the subject.

PMID- 28751533
TI  - Fifteen-minute consultation: stabilisation of the high-risk newborn infant beside
      the mother.
AB  - Paediatric and adult resuscitation is often performed with family present.
      Current guidelines recommend deferred umbilical cord clamping as part of
      immediate neonatal care, requiring neonatal assessment next to the mother. This
      paper describes strategies for providing care beside the mother using both
      standard resuscitation equipment and a trolley designed for this purpose.

PMID- 28751534
TI  - Bedside ultrasound improves the success rate of lumbar puncture in infants.

PMID- 28751535
TI  - How to use tests for disorders of copper metabolism.
AB  - In paediatrics, one of our main aims in the diagnostic process is to identify any
      treatable conditions. The copper metabolism disorder Wilson's disease (WD) is one
      such condition that is caused by mutations in the ATP7B gene. Delay in treatment
      could result in irreversible disability or even death. Although liver disease is
      the most common presenting feature in children, some children may initially
      present with a subtle neurological presentation only. In patients presenting with
      dystonia, tremor, dysarthria or with a deterioration in school performance, there
      should be a high index of suspicion for WD. However, the differential of these
      clinical presentations is wide and exclusion of WD is difficult. No single
      diagnostic test can exclude WD and each of the biochemical tests has limitations.
      In this article, we discuss copper metabolism disorders including WD and Menke's
      disease. We then discuss the available diagnostic tests and how to investigate
      children for these rare disorders.

PMID- 28751536
TI  - Defective sperm head decondensation undermines the success of ICSI in the bovine.
AB  - The efficiency of intracytoplasmic sperm injection (ICSI) in the bovine is low
      compared to other species. It is unknown whether defective oocyte activation
      and/or sperm head decondensation limit the success of this technique in this
      species. To elucidate where the main obstacle lies, we used homologous and
      heterologous ICSI and parthenogenetic activation procedures. We also evaluated
      whether in vitro maturation negatively impacted the early stages of activation
      after ICSI. Here we showed that injected bovine sperm are resistant to nuclear
      decondensation by bovine oocytes and this is only partly overcome by exogenous
      activation. Remarkably, when we used heterologous ICSI, in vivo-matured mouse
      eggs were capable of mounting calcium oscillations and displaying normal PN
      formation following injection of bovine sperm, although in vitro-matured mouse
      oocytes were unable to do so. Together, our data demonstrate that bovine sperm
      are especially resistant to nuclear decondensation by in vitro-matured oocytes
      and this deficiency cannot be simply overcome by exogenous activation protocols,
      even by inducing physiological calcium oscillations. Therefore, the inability of
      a suboptimal ooplasmic environment to induce sperm head decondensation limits the
      success of ICSI in the bovine. Studies aimed to improve the cytoplasmic milieu of
      in vitro-matured oocytes and to replicate the molecular changes associated with
      in vivo capacitation and acrosome reaction will deepen our understanding of the
      mechanism of fertilization and improve the success of ICSI in this species.

PMID- 28751537
TI  - Management of Kawasaki disease in adults.
AB  - Kawasaki disease is the most common childhood vasculitis in the USA and the most
      common cause of acquired cardiac disease in children in developed countries.
      Since the vast majority of Kawasaki disease initially presents at <5 years of
      age, many adult cardiologists are unfamiliar with the pathophysiology of this
      disease. This vasculitis has a predilection for coronary arteries with a high
      complication rate across the lifespan for those with medium to large coronary
      artery aneurysms. An inflammatory cascade produces endothelial dysfunction and
      damage to the vascular wall, leading to aneurysmal dilatation. Later,
      pseudonormalisation of the vascular lumen occurs through vascular remodelling and
      layering thrombus, but this does not necessarily indicate resolution of disease
      or reduction of risk for future complications. There is a growing prevalence of
      Kawasaki disease, making it increasingly relevant for adult cardiologists as this
      population transitions into adulthood. As the 2017 American Heart Association
      (AHA) and 2014 Japanese Circulation Society (JCS) guidelines emphasise, Kawasaki
      disease requires rigorous follow-up with cardiac stress testing and non-invasive
      imaging to detect progressive stenosis, thrombosis and luminal occlusion that may
      lead to myocardial ischaemia and infarction. Due to differences in disease
      mechanisms, coronary disease due to Kawasaki disease should be managed with
      different pharmacological and non-pharmacological treatment algorithms than
      atherosclerotic coronary disease. This review addresses gaps in the current
      knowledge of the disease and its optimal treatment, differences in the AHA and
      JCS guidelines, targets for future research and obstacles to transition of care
      from adolescence into adulthood.

PMID- 28751538
TI  - Coronary anatomy in children with bicuspid aortic valves and associated
      congenital heart disease.
AB  - OBJECTIVE: In patients with bicuspid aortic valve (BAV), coronary anatomy is
      variable. High take-off coronary arteries have been described, but data are
      scarce, especially when associated with complex congenital heart disease (CHD).
      The purpose of this study was to describe coronary patterns in these patients.
      METHODS: In 84 postmortem heart specimens with BAV and associated CHD, position
      and height of the coronary ostia were studied and related to BAV morphology.
      RESULTS: High take-off right (RCA) and left coronary arteries (LCA) were observed
      in 23% and 37% of hearts, respectively, most frequently in hearts with
      hypoplastic left ventricle (HLV) and outflow tract anomalies. In HLV, high take
      off was observed in 18/40 (45%) more frequently of LCA (n=14) than RCA (n=6). In
      hearts with aortic hypoplasia, 8/13 (62%) had high take-off LCA and 6/13 (46%)
      high take-off RCA. High take-off was seen 19 times in 22 specimens with
      perimembranous ventricular septal defect (RCA 8, LCA 11). High take-off was
      associated with type 1A BAV (raphe between right and left coronary leaflets),
      more outspoken for the RCA. Separate ostia of left anterior descending coronary
      artery and left circumflex coronary artery were seen in four hearts (5%), not
      related to specific BAV morphology. CONCLUSION: High take-off coronary arteries,
      especially the LCA, occur more frequently in BAV with associated CHD than
      reported in normal hearts and isolated BAV. Outflow tract defects and HLV are
      associated with type 1A BAV and high take-off coronary arteries. Although it is
      unclear whether these findings in infants with detrimental outcome can be related
      to surviving adults, clinical awareness of variations in coronary anatomy is
      warranted.

PMID- 28751539
TI  - Mechanisms of Resistance to NTRK Inhibitors and Therapeutic Strategies in NTRK1
      Rearranged Cancers.
AB  - Neurotrophic receptor tyrosine kinase 1 (NTRK1) gene rearrangement leads to
      constitutive activation of NTRK1, which induces high-transforming ability. NTRK
      rearranged cancers have been identified in several cancer types, such as
      glioblastoma, non-small cell lung cancer, and colorectal cancer. Although there
      are currently no clinically approved inhibitors that target NTRK1, several
      tyrosine kinase inhibitors (TKI), such as entrectinib and LOXO-101, are in
      clinical trials. The purpose of this study was to identify potential mechanisms
      of resistance to NTRK inhibitors and find potential therapeutic strategies to
      overcome the resistance. We examined the sensitivity of TPM3-NTRK1-transformed
      Ba/F3 cells and TPM3-NTRK1-harboring KM12 cells to multiple NTRK inhibitors.
      Acquired NTRK inhibitor-resistant mutations were screened by N-ethyl-N
      nitrosourea mutagenesis with Ba/F3-TPM3-NTRK1 cells or by the establishment of
      NTRK-TKI-resistant cells from KM12 cells continuously treated with NTRK-TKIs. We
      identified multiple novel NTRK-TKI resistance mutations in the NTRK1 kinase
      domain, including G595R, and insulin growth factor receptor type 1 (IGF1R) bypass
      pathway-mediated resistance. After identifying the resistance mechanisms, we
      performed drug screening with small-molecule inhibitors to overcome the
      resistance. As a result, we found that ponatinib and nintedanib effectively
      inhibited the survival of TPM3-NTRK1-G667C but not G595R mutants, both of which
      showed resistance to entrectinib or larotrectinib (LOXO-101). Furthermore,
      cabozantinib with an IGF1R inhibitor such as OSI-906 could overcome bypass
      pathway-mediated resistance. We developed a comprehensive model of acquired
      resistance to NTRK inhibitors in cancer with NTRK1 rearrangement and identified
      cabozantinib as a therapeutic strategy to overcome the resistance. Mol Cancer
      Ther; 16(10); 2130-43. (c)2017 AACR.

PMID- 28751540
TI  - TTK Inhibitors as a Targeted Therapy for CTNNB1 (beta-catenin) Mutant Cancers.
AB  - The spindle assembly checkpoint kinase TTK (Mps1) is a key regulator of
      chromosome segregation and is the subject of novel targeted therapy approaches by
      small-molecule inhibitors. Although the first TTK inhibitors have entered phase I
      dose escalating studies in combination with taxane chemotherapy, a patient
      stratification strategy is still missing. With the aim to identify a genomic
      biomarker to predict the response of tumor cells to TTK inhibitor therapy, we
      profiled a set of preclinical and clinical TTK inhibitors from different chemical
      series on a panel of 66 genetically characterized cell lines derived from
      different tumors (Oncolines). Cell lines harboring activating mutations in the
      CTNNB1 gene, encoding the Wnt pathway signaling regulator beta-catenin, were on
      average up to five times more sensitive to TTK inhibitors than cell lines wild
      type for CTNNB1 The association of CTNNB1-mutant status and increased cancer cell
      line sensitivity to TTK inhibition was confirmed with isogenic cell line pairs
      harboring either mutant or wild-type CTNNB1 Treatment of a xenograft model of a
      CTNNB1-mutant cell line with the TTK inhibitor NTRC 0066-0 resulted in complete
      inhibition of tumor growth. Mutations in CTNNB1 occur at relatively high
      frequency in endometrial cancer and hepatocellular carcinoma, which are known to
      express high TTK levels. We propose mutant CTNNB1 as a prognostic drug response
      biomarker, enabling the selection of patients most likely to respond to TTK
      inhibitor therapy in proof-of-concept clinical trials. Mol Cancer Ther; 16(11);
      2609-17. (c)2017 AACR.

PMID- 28751541
TI  - Downregulation of Cavin-1 Expression via Increasing Caveolin-1 Degradation
      Prompts the Proliferation and Migration of Vascular Smooth Muscle Cells in
      Balloon Injury-Induced Neointimal Hyperplasia.
AB  - BACKGROUND: Percutaneous coronary intervention has been widely used in the
      treatment of ischemic heart disease, but vascular restenosis is a main limitation
      of percutaneous coronary intervention. Our previous work reported that caveolin-1
      had a key functional role in intimal hyperplasia, whereas whether Cavin-1
      (another important caveolae-related protein) was involved is still unknown.
      Therefore, we will investigate the effect of Cavin-1 on neointimal formation.
      METHODS AND RESULTS: Balloon injury markedly reduced Cavin-1 protein and enhanced
      ubiquitin protein expression accompanied with neointimal hyperplasia in injured
      carotid arteries, whereas Cavin-1 mRNA had no change. In cultured vascular smooth
      muscle cells (VSMCs), Cavin-1 was downregulated after inhibition of protein
      synthesis by cycloheximide, which was distinctly prevented by pretreatment with
      proteasome inhibitor MG132 but not by lysosomal inhibitor chloroquine, suggesting
      that proteasomal degradation resulted in Cavin-1 downregulation. Knockdown of
      Cavin-1 by local injection of Cavin-1 short hairpin RNA (shRNA) into balloon
      injured carotid arteries in vivo promoted neointimal formation. In addition,
      inhibition or overexpression of Cavin-1 in cultured VSMCs in vitro prompted or
      suppressed VSMC proliferation and migration via increasing or decreasing
      extracellular signal-regulated kinase phosphorylation and matrix-degrading
      metalloproteinases-9 activity, respectively. However, under basic conditions, the
      effect of Cavin-1 on VSMC migration was stronger than on proliferation. Moreover,
      our results indicated that Cavin-1 regulated caveolin-1 expression via lysosomal
      degradation pathway. CONCLUSIONS: Our study revealed the role and the mechanisms
      of Cavin-1 downregulation in neointimal formation by promoting VSMC
      proliferation, migration, and synchronously enhancing caveolin-1 lysosomal
      degradation. Cavin-1 may be a potential therapeutic target for the treatment of
      postinjury vascular remodeling.

PMID- 28751542
TI  - Kinetics of Circulating MicroRNAs in Response to Cardiac Stress in Patients With
      Coronary Artery Disease.
AB  - BACKGROUND: Circulating microRNAs (miRNAs/miRs) are regulated in patients with
      coronary artery disease. The impact of transient coronary ischemia on circulating
      miRNA levels is unknown. We aimed to investigate circulating miRNA kinetics in
      response to cardiac stress in patients with or without significant coronary
      stenosis. METHODS AND RESULTS: Eighty of 105 screened patients with stable
      coronary artery disease underwent dobutamine stress echocardiography before
      coronary angiography. Nine circulating vascular miRNAs (miRNA-21, miRNA-26, miRNA
      27a, miRNA-92a, miRNA-126-3p, miRNA-133a, miRNA-222, miRNA-223, and miRNA-199-5p)
      were quantified in plasma by reverse transcription polymerase chain reaction
      before, immediately after, and 4 and 24 hours after dobutamine stress
      echocardiography. Quantitative polymerase chain reaction revealed increased miRNA
      21, miRNA-126-3p, and miRNA-222 levels at 24 hours after dobutamine stress
      echocardiography in all patients. On coronary angiography, significant coronary
      artery stenoses (>80% diameter stenosis) were found in 41 patients. Stratifying
      patients according to the prevalence of significant stenoses, patients with
      stenosis showed an increase of circulating miRNA-21, miRNA-126-3p, and miRNA-222
      in response to cardiac stress. In patients without significant stenoses (<50%
      diameter stenosis), miRNA-92a levels gradually increased in response to cardiac
      stress. CONCLUSIONS: miRNAs are distinctly released into the circulation in
      response to cardiac stress depending on the prevalence of significant coronary
      stenoses.

PMID- 28751543
TI  - ADPase CD39 Fused to Glycoprotein VI-Fc Boosts Local Antithrombotic Effects at
      Vascular Lesions.
AB  - BACKGROUND: GPVI (Glycoprotein VI) is the essential platelet collagen receptor in
      atherothrombosis. Dimeric GPVI-Fc (Revacept) binds to GPVI binding sites on
      plaque collagen. As expected, it did not increase bleeding in clinical studies.
      GPVI-Fc is a potent inhibitor of atherosclerotic plaque-induced platelet
      aggregation at high shear flow, but its inhibition at low shear flow is limited.
      We sought to increase the platelet inhibitory potential by fusing GPVI-Fc to the
      ectonucleotidase CD39 (fusion protein GPVI-CD39), which inhibits local ADP
      accumulation at vascular plaques, and thus to create a lesion-directed dual
      antiplatelet therapy that is expected to lack systemic bleeding risks. METHODS
      AND RESULTS: GPVI-CD39 effectively stimulated local ADP degradation and, compared
      with GPVI-Fc alone, led to significantly increased inhibition of ADP-, collagen-,
      and human plaque-induced platelet aggregation in Multiplate aggregometry and
      plaque-induced platelet thrombus formation under arterial flow conditions. GPVI
      CD39 did not increase bleeding time in an in vitro assay simulating primary
      hemostasis. In a mouse model of ferric chloride-induced arterial thrombosis, GPVI
      CD39 effectively delayed vascular thrombosis but did not increase tail bleeding
      time in vivo. CONCLUSIONS: GPVI-CD39 is a novel approach to increase local
      antithrombotic activity at sites of atherosclerotic plaque rupture or injury. It
      enhances GPVI-Fc-mediated platelet inhibition and presents a potentially
      effective and safe molecule for the treatment of acute atherothrombotic events,
      with a favorable risk-benefit ratio.

PMID- 28751544
TI  - The Impact of Cryoballoon Versus Radiofrequency Ablation for Paroxysmal Atrial
      Fibrillation on Healthcare Utilization and Costs: An Economic Analysis From the
      FIRE AND ICE Trial.
AB  - BACKGROUND: This study sought to assess payer costs following cryoballoon or
      radiofrequency current (RFC) catheter ablation of paroxysmal atrial fibrillation
      in the randomized FIRE AND ICE trial. METHODS AND RESULTS: A trial period
      analysis of healthcare costs evaluated the impact of ablation modality
      (cryoballoon versus RFC) on differences in resource use and associated payer
      costs. Analyses were based on repeat interventions, rehospitalizations, and
      cardioversions during the trial, with unit costs based on 3 national healthcare
      systems (Germany [?], the United Kingdom [L], and the United States [$]). Total
      payer costs were calculated by applying standard unit costs to hospital stays,
      using International Classification of Diseases, 10th Revision diagnoses and
      procedure codes that were mapped to country-specific diagnosis-related groups.
      Patients (N=750) randomized 1:1 to cryoballoon (n=374) or RFC (n=376) ablation
      were followed for a mean of 1.5 years. Resource use was lower in the cryoballoon
      than the RFC group (205 hospitalizations and/or interventions in 122 patients
      versus 268 events in 154 patients). The cost differences per patient in mean
      total payer costs during follow-up were ?640, L364, and $925 in favor of
      cryoballoon ablation (P=0.012, 0.013, and 0.016, respectively). This resulted in
      trial period total cost savings of ?245 000, L140 000, and $355 000. CONCLUSIONS:
      When compared with RFC ablation, cryoballoon ablation was associated with a
      reduction in resource use and payer costs. In all 3 national healthcare systems
      analyzed, this reduction resulted in substantial trial period cost savings,
      primarily attributable to fewer repeat ablations and a reduction in
      cardiovascular rehospitalizations with cryoballoon ablation. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Identifier: NCT01490814.

PMID- 28751546
TI  - Children are being failed by substandard mental health services.

PMID- 28751545
TI  - Angiotensin II Type 1 Receptor-Associated Protein Regulates Kidney Aging and
      Lifespan Independent of Angiotensin.
AB  - BACKGROUND: The kidney is easily affected by aging-associated changes, including
      glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Particularly,
      renal tubulointerstitial fibrosis is a final common pathway in most forms of
      progressive renal disease. Angiotensin II type 1 receptor (AT1R)-associated
      protein (ATRAP), which was originally identified as a molecule that binds to
      AT1R, is highly expressed in the kidney. Previously, we have shown that ATRAP
      suppresses hyperactivation of AT1R signaling, but does not affect physiological
      AT1R signaling. METHODS AND RESULTS: We hypothesized that ATRAP has a novel
      functional role in the physiological age-degenerative process, independent of
      modulation of AT1R signaling. ATRAP-knockout mice were used to study the
      functional involvement of ATRAP in the aging. ATRAP-knockout mice exhibit a
      normal age-associated appearance without any evident alterations in physiological
      parameters, including blood pressure and cardiovascular and metabolic phenotypes.
      However, in ATRAP-knockout mice compared with wild-type mice, the following takes
      place: (1) age-associated renal function decline and tubulointerstitial fibrosis
      are more enhanced; (2) renal tubular mitochondrial abnormalities and subsequent
      increases in the production of reactive oxygen species are more advanced; and (3)
      life span is 18.4% shorter (median life span, 100.4 versus 123.1 weeks). As a key
      mechanism, age-related pathological changes in the kidney of ATRAP-knockout mice
      correlated with decreased expression of the prosurvival gene, Sirtuin1. On the
      other hand, chronic angiotensin II infusion did not affect renal sirtuin1
      expression in wild-type mice. CONCLUSIONS: These results indicate that ATRAP
      plays an important role in inhibiting kidney aging, possibly through sirtuin1
      mediated mechanism independent of blocking AT1R signaling, and further protecting
      normal life span.

PMID- 28751547
TI  - Defects in alpha-Cell Function in Patients With Diabetes Due to Chronic
      Pancreatitis Compared With Patients With Type 2 Diabetes and Healthy Individuals.
AB  - OBJECTIVE: Diabetes frequently develops in patients with chronic pancreatitis. We
      examined the alterations in the glucagon response to hypoglycemia and to oral
      glucose administration in patients with diabetes due to chronic pancreatitis.
      RESEARCH DESIGN AND METHODS: Ten patients with diabetes secondary to chronic
      pancreatitis were compared with 13 patients with type 2 diabetes and 10 healthy
      control subjects. A stepwise hypoglycemic clamp and an oral glucose tolerance
      test (OGTT) were performed. RESULTS: Glucose levels during the OGTT were higher
      in patients with diabetes and chronic pancreatitis and lower in control subjects
      (P < 0.0001). Insulin and C-peptide levels were reduced, and the glucose-induced
      suppression of glucagon was impaired in both groups with diabetes (all P < 0.0001
      vs. control subjects). During hypoglycemia, glucagon concentrations were reduced
      in patients with chronic pancreatitis and with type 2 diabetes (P < 0.05). The
      increase in glucagon during the clamp was inversely related to the glucose
      induced glucagon suppression and positively related to beta-cell function. Growth
      hormone responses to hypoglycemia were lower in patients with type 2 diabetes (P
      = 0.0002) but not in patients with chronic pancreatitis. CONCLUSIONS: alpha-Cell
      responses to oral glucose ingestion and to hypoglycemia are disturbed in patients
      with diabetes and chronic pancreatitis and in patients with type 2 diabetes. The
      similarities between these defects suggest a common etiology.

PMID- 28751548
TI  - Comparison of Ipragliflozin and Pioglitazone Effects on Nonalcoholic Fatty Liver
      Disease in Patients With Type 2 Diabetes: A Randomized, 24-Week, Open-Label,
      Active-Controlled Trial.
AB  - OBJECTIVE: To compare the efficacy of ipragliflozin versus pioglitazone in
      patients with type 2 diabetes complicated by nonalcoholic fatty liver disease
      (NAFLD). RESEARCH DESIGN AND METHODS: In this open-label, randomized, active
      controlled trial, we randomly assigned 66 patients with type 2 diabetes and NAFLD
      to receive ipragliflozin 50 mg (n = 32) or pioglitazone 15-30 mg (n = 34) orally
      once daily. The primary outcome was a change from baseline in the liver-to-spleen
      attenuation ratio (L/S ratio) on computed tomography at week 24. RESULTS: At week
      24, the mean +/- SD L/S ratio had increased by 0.22 (from 0.80 +/- 0.24 to 1.00
      +/- 0.18) in the ipragliflozin group and 0.21 (from 0.78 +/- 0.26 to 0.98 +/-
      0.16) in the pioglitazone group (P = 0.90). Serum aspartate and alanine
      aminotransferase levels, HbA1c, and fasting plasma glucose were similarly reduced
      in the two treatment groups. Nevertheless, body weight and visceral fat area
      showed significant reductions only in the ipragliflozin group compared with the
      pioglitazone group (P < 0.0001 and P = 0.0013, respectively). There were no
      serious adverse events in either group. CONCLUSIONS: Compared with pioglitazone,
      ipragliflozin exerts equally beneficial effects on NAFLD and glycemic control
      during the treatment of patients with type 2 diabetes complicated by NAFLD.
      Furthermore, ipragliflozin significantly reduced body weight and abdominal fat
      area.

PMID- 28751549
TI  - Cross-talk of Brassinosteroid signaling in controlling growth and stress
      responses.
AB  - Plants are faced with a barrage of stresses in their environment and must
      constantly balance their growth and survival. As such, plants have evolved
      complex control systems that perceive and respond to external and internal
      stimuli in order to optimize these responses, many of which are mediated by
      signaling molecules such as phytohormones. One such class of molecules called
      Brassinosteroids (BRs) are an important group of plant steroid hormones involved
      in numerous aspects of plant life including growth, development and response to
      various stresses. The molecular determinants of the BR signaling pathway have
      been extensively defined, starting with the membrane-localized receptor BRI1 and
      co-receptor BAK1 and ultimately culminating in the activation of BES1/BZR1 family
      transcription factors, which direct a transcriptional network controlling the
      expression of thousands of genes enabling BRs to influence growth and stress
      programs. Here, we highlight recent progress in understanding the relationship
      between the BR pathway and plant stress responses and provide an integrated view
      of the mechanisms mediating cross-talk between BR and stress signaling.

PMID- 28751550
TI  - Novel targeted therapies for cancer cachexia.
AB  - Anorexia and metabolic alterations are the main components of the cachectic
      syndrome. Glucose intolerance, fat depletion, muscle protein catabolism and other
      alterations are involved in the development of cancer cachexia, a multi-organ
      syndrome. Nutritional approach strategies are not satisfactory in reversing the
      cachectic syndrome. The aim of the present review is to deal with the recent
      therapeutic targeted approaches that have been designed to fight and counteract
      wasting in cancer patients. Indeed, some promising targeted therapeutic
      approaches include ghrelin agonists, selective androgen receptor agonists, beta
      blockers and antimyostatin peptides. However, a multi-targeted approach seems
      absolutely essential to treat patients affected by cancer cachexia. This approach
      should not only involve combinations of drugs but also nutrition and an adequate
      program of physical exercise, factors that may lead to a synergy, essential to
      overcome the syndrome. This may efficiently reverse the metabolic changes
      described above and, at the same time, ameliorate the anorexia. Defining this
      therapeutic combination of drugs/nutrients/exercise is an exciting project that
      will stimulate many scientific efforts. Other aspects that will, no doubt, be
      very important for successful treatment of cancer wasting will be an optimized
      design of future clinical trials, together with a protocol for staging cancer
      patients in relation to their degree of cachexia. This will permit that
      nutritional/metabolic/pharmacological support can be started early in the course
      of the disease, before severe weight loss occurs. Indeed, timing is crucial and
      has to be taken very seriously when applying the therapeutic approach.

PMID- 28751551
TI  - A quick guide to effective grassroots advocacy for scientists.
AB  - The current political climate in the United States has mobilized scientists to
      become more cognizant of the need to advocate for sustainable science funding
      from the federal government and for acceptance of evidence-based policy making
      that relies on the best available scientific data. Many scientists, however, do
      not learn about science policy or how to advocate in Washington, D.C., or at the
      local level as part of their scientific training. Here we explain why science
      advocacy is important and provide steps on how to get involved by communicating
      with elected officials and engaging in the local community.

PMID- 28751552
TI  - Plasma Glial Fibrillary Acidic Protein in the Differential Diagnosis of
      Intracerebral Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Plasma GFAP (glial fibrillary acidic protein) has
      recently emerged as a potential biomarker for the differentiation of acute
      intracerebral hemorrhage (ICH) from acute ischemic stroke (AIS). We prospectively
      assessed the diagnostic accuracy of GFAP in the differential diagnosis of ICH.
      METHODS: Consecutive patients presenting to the emergency department within 6
      hours from symptom onset were evaluated. All patients underwent extensive
      diagnostic work-up and were classified according to discharge diagnosis in AIS,
      ICH, subarachnoid hemorrhage, and stroke mimics. GFAP was also measured in
      healthy volunteers (controls). Baseline stroke severity was evaluated using
      National Institutes of Health Stroke Scale. Receiver operating characteristic
      curve analysis was used to identify the optimal cutoff point for the
      differentiation between subgroups. Correlation analyses of GFAP plasma
      concentrations with baseline National Institutes of Health Stroke Scale and onset
      to sampling time were performed with the nonparametric Spearman rank test and
      fractional polynomial regression, respectively. RESULTS: Our study population
      consisted of 270 individuals (AIS: 121, ICH: 34, stroke mimics: 31, subarachnoid
      hemorrhage: 5, controls: 79). No differences on baseline stroke severity and
      onset to sampling time were detected between AIS and ICH. Higher median plasma
      GFAP values were documented in ICH compared with AIS, stroke mimics, and controls
      (P<0.001). Receiver operating characteristic analysis highlighted a cutoff value
      of 0.43 ng/mL as the optimal threshold for the differentiation between ICH and
      AIS (sensitivity: 91%, specificity: 97%). No association was detected between
      plasma GFAP concentrations and baseline stroke severity for both AIS (P=0.515)
      and ICH (P=0.387). In the fractional polynomial analysis, the association between
      GFAP concentration and onset to sampling time was best described by a J-shaped
      curve for AIS and an inverted U-shaped curve for ICH, with a peak at 2 hours.
      CONCLUSIONS: Plasma GFAP seems to be a sensitive and specific biomarker for the
      differentiation of ICH from both AIS and other acute neurological disorders, with
      the optimal diagnostic yield being present in the second hour from symptom onset.

PMID- 28751553
TI  - Towards Improved Translational Stroke Research: Progress and Perspectives of the
      Recent National Institute of Neurological Disorders and Stroke Consensus Group
      Meeting.

PMID- 28751555
TI  - High Appraisal of Methodological Quality of Basic Science Articles Published in
      Stroke.

PMID- 28751554
TI  - Translational Stroke Research: Vision and Opportunities.

PMID- 28751556
TI  - ARID1A mutation in blastic plasmacytoid dendritic cell neoplasm.

PMID- 28751557
TI  - The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone
      activity in in vitro and in vivo models of multiple myeloma by blockade of Ikaros
      and MYC signaling.
AB  - Most patients with multiple myeloma treated with current therapies, including
      immunomodulatory drugs, eventually develop relapsed/refractory disease. Clinical
      activity of lenalidomide relies on degradation of Ikaros and the consequent
      reduction in IRF4 expression, both required for myeloma cell survival and
      involved in the regulation of MYC transcription. Thus, we sought to determine the
      combinational effect of an MYC-interfering therapy with
      lenalidomide/dexamethasone. We analyzed the potential therapeutic effect of the
      combination of the BET bromodomain inhibitor CPI203 with the
      lenalidomide/dexamethasone regimen in myeloma cell lines. CPI203 exerted a dose
      dependent cell growth inhibition in cell lines, indeed in
      lenalidomide/dexamethasone-resistant cells (median response at 0.5 MUM: 65.4%),
      characterized by G1 cell cycle blockade and a concomitant inhibition of MYC and
      Ikaros signaling. These effects were potentiated by the addition of
      lenalidomide/dexamethasone. Results were validated in primary plasma cells from
      patients with multiple myeloma co-cultured with the mesenchymal stromal cell line
      stromaNKtert. Consistently, the drug combination evoked a 50% reduction in cell
      proliferation and correlated with basal Ikaros mRNA expression levels (P=0.04).
      Finally, in a SCID mouse xenotransplant model of myeloma, addition of CPI203 to
      lenalidomide/dexamethasone decreased tumor burden, evidenced by a lower glucose
      uptake and increase in the growth arrest marker GADD45B, with simultaneous
      downregulation of key transcription factors such as MYC, Ikaros and IRF4. Taken
      together, our data show that the combination of a BET bromodomain inhibitor with
      a lenalidomide-based regimen may represent a therapeutic approach to improve the
      response in relapsed/refractory patients with multiple myeloma, even in cases
      with suboptimal prior response to immunomodulatory drugs.

PMID- 28751558
TI  - Characterization of atrial fibrillation adverse events reported in ibrutinib
      randomized controlled registration trials.
AB  - The first-in-class Bruton's tyrosine kinase inhibitor ibrutinib has proven
      clinical benefit in B-cell malignancies; however, atrial fibrillation (AF) has
      been reported in 6-16% of ibrutinib patients. We pooled data from 1505 chronic
      lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large,
      randomized, controlled studies to characterize AF with ibrutinib and its
      management. AF incidence was 6.5% [95% Confidence Interval (CI): 4.8, 8.5] for
      ibrutinib at 16.6-months versus 1.6% (95%CI: 0.8, 2.8) for comparator and 10.4%
      (95%CI: 8.4, 12.9) at the 36-month follow up; estimated cumulative incidence:
      13.8% (95%CI: 11.2, 16.8). Ibrutinib treatment, prior history of AF and age 65
      years or over were independent risk factors for AF. Multiple AF events were more
      common with ibrutinib (44.9%; comparator, 16.7%) among patients with AF. Most
      (85.7%) patients with AF did not discontinue ibrutinib, and more than half
      received common anticoagulant/antiplatelet medications on study. Low-grade bleeds
      were more frequent with ibrutinib, but serious bleeds were uncommon (ibrutinib,
      2.9%; comparator, 2.0%). Although the AF rate among older non-trial patients with
      comorbidities is likely underestimated by this dataset, these results suggest
      that AF among clinical trial patients is generally manageable without ibrutinib
      discontinuation (clinicaltrials.gov identifier: 01578707, 01722487, 01611090,
      01646021).

PMID- 28751560
TI  - Mutational status of IGHV is the most reliable prognostic marker in trisomy 12
      chronic lymphocytic leukemia.

PMID- 28751559
TI  - Loss-of-function but not dominant-negative intragenic IKZF1 deletions are
      associated with an adverse prognosis in adult BCR-ABL-negative acute
      lymphoblastic leukemia.
AB  - Genetic alterations of the transcription factor IKZF1 ("IKAROS") are detected in
      around 15-30% of cases of BCR-ABL-negative B-cell precursor acute lymphoblastic
      leukemia. Different types of intragenic deletions have been observed, resulting
      in a functionally inactivated allele ("loss-of-function") or in "dominant
      negative" isoforms. The prognostic impact of these alterations especially in
      adult acute lymphoblastic leukemia is not well defined. We analyzed 482 well
      characterized cases of adult BCR-ABL-negative B-precursor acute lymphoblastic
      leukemia uniformly treated in the framework of the GMALL studies and detected
      IKZF1 alterations in 128 cases (27%). In 20%, the IKZF1 alteration was present in
      a large fraction of leukemic cells ("high deletion load") while in 7% it was
      detected only in small subclones ("low deletion load"). Some patients showed more
      than one IKZF1 alteration (8%). Patients exhibiting a loss-of-function isoform
      with high deletion load had a shorter overall survival (OS at 5 years 28% vs.
      59%; P<0.0001), also significant in a subgroup analysis of standard risk patients
      according to GMALL classification (OS at 5 years 37% vs. 68%; P=0.0002). Low
      deletion load or dominant-negative IKZF1 alterations had no prognostic impact.
      The results thus suggest that there is a clear distinction between loss-of
      function and dominant-negative IKZF1 deletions. Affected patients should thus be
      monitored for minimal residual disease carefully to detect incipient relapses at
      an early stage and they are potential candidates for alternative or intensified
      treatment regimes. (clinicaltrials.gov identifiers: 00199056 and 00198991).

PMID- 28751561
TI  - Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2,
      TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma.
AB  - Splenic diffuse red pulp lymphoma is an indolent small B-cell lymphoma recognized
      as a provisional entity in the World Health Organization 2008 classification. Its
      precise relationship to other related splenic B-cell lymphomas with frequent
      leukemic involvement or other lymphoproliferative disorders remains undetermined.
      We performed whole-exome sequencing to explore the genetic landscape of ten cases
      of splenic diffuse red pulp lymphoma using paired tumor and normal samples. A
      selection of 109 somatic mutations was then evaluated in a cohort including 42
      samples of splenic diffuse red pulp lymphoma and compared to those identified in
      46 samples of splenic marginal zone lymphoma and eight samples of hairy-cell
      leukemia. Recurrent mutations or losses in BCOR (the gene encoding the BCL6
      corepressor) - frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy
      number loss (n=4) - were identified in 10/42 samples of splenic diffuse red pulp
      lymphoma (24%), whereas only one frameshift mutation was identified in 46 cases
      of splenic marginal zone lymphoma (2%). Inversely, KLF2, TNFAIP3 and MYD88,
      common mutations in splenic marginal zone lymphoma, were rare (one KLF2 mutant in
      42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse red pulp
      lymphoma. These findings define an original genetic profile of splenic diffuse
      red pulp lymphoma and suggest that the mechanisms of pathogenesis of this
      lymphoma are distinct from those of splenic marginal zone lymphoma and hairy-cell
      leukemia.

PMID- 28751562
TI  - Impact of prior therapy on the efficacy and safety of oral ixazomib-lenalidomide
      dexamethasone vs. placebo-lenalidomide-dexamethasone in patients with
      relapsed/refractory multiple myeloma in TOURMALINE-MM1.
AB  - Prior treatment exposure in patients with relapsed/refractory multiple myeloma
      may affect outcomes with subsequent therapies. We analyzed efficacy and safety
      according to prior treatment in the phase 3 TOURMALINE-MM1 study of ixazomib
      lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd. Patients with
      relapsed/refractory multiple myeloma received ixazomib-Rd or placebo-Rd. Efficacy
      and safety were evaluated in subgroups defined according to type (proteasome
      inhibitor [PI] and immunomodulatory drug) and number (1 vs. 2 or 3) of prior
      therapies received. Of 722 patients, 503 (70%) had received a prior PI, and 397
      (55%) prior lenalidomide/thalidomide; 425 patients had received 1 prior therapy,
      and 297 received 2 or 3 prior therapies. At a median follow up of ~15 months, PFS
      was prolonged with ixazomib-Rd vs. placebo-Rd regardless of type of prior therapy
      received; HR 0.739 and 0.749 in PI-exposed and -naive patients, HR 0.744 and
      0.700 in immunomodulatory-drug-exposed and -naive patients, respectively. PFS
      benefit with ixazomib-Rd vs. placebo-Rd appeared greater in patients with 2 or 3
      prior therapies (HR 0.58) and in those with 1 prior therapy without prior
      transplant (HR 0.60) versus those with 1 prior therapy and transplant (HR 1.23).
      Across all subgroups, toxicity was consistent with that seen in the intent-to
      treat population. In patients with relapsed/refractory multiple myeloma, ixazomib
      Rd was associated with a consistent clinical benefit vs. placebo-Rd regardless of
      prior treatment with bortezomib or immunomodulatory drugs. Patients with 2 or 3
      prior therapies, or 1 prior therapy without transplant seemed to have greater
      benefit than patients with 1 prior therapy and transplant. TOURMALINE-MM1
      registered at clinicaltrials.gov identifier: 01564537.

PMID- 28751563
TI  - Calreticulin as a novel B-cell receptor antigen in chronic lymphocytic leukemia.

PMID- 28751564
TI  - Increase of von Willebrand factor with aging in type 1 von Willebrand disease:
      fact or fiction?

PMID- 28751565
TI  - Incidence and outcome of acquired aplastic anemia: real-world data from patients
      diagnosed in Sweden from 2000-2011.
AB  - A plastic anemia is a rare life-threatening disease. However, since the
      introduction of immunosuppressive therapy and allogeneic stem cell
      transplantation, the outcome has improved considerably, and the 5-year survival
      is reported to be 70-80% in selected patient cohorts. Yet, contemporary
      population-based data on incidence and survival are lacking. We performed a
      national retrospective study to determine the incidence, treatment, and survival
      of patients with aplastic anemia diagnosed in Sweden from 2000-2011. Patients
      were included via the National Patient Registry, and diagnosed according to the
      Camitta criteria. In total, 257 confirmed cases were identified, with an overall
      incidence of 2.35 (95% CI: 2.06-2.64) cases per million inhabitants per year.
      Median age was 60 years (range: 2-92), and median follow up was 76 (0-193)
      months. Primary treatments included immunosuppressive therapy (63%), allogenic
      stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy
      (27%). The 5-year survival was 90.7% in patients aged 0-18 years, 90.5% in
      patients aged 19-39 years, 70.7% in patients aged 40-59 years, and 38.1% in
      patients aged >=60 years. Multivariate analysis showed that age (both 40-59 and
      >=60 age groups), very severe aplastic anemia and single-agent cyclosporine/no
      specific therapy were independent risk factors for inferior survival. In
      conclusion, younger aplastic anemia patients experience a very good long-term
      survival, while that of patients >=60 years in particular remains poor.
      Apparently, the challenge today is to improve the management of older aplastic
      anemia patients, and prospective studies to address this medical need are
      warranted.

PMID- 28751566
TI  - Prolonged versus standard native E. coli asparaginase therapy in childhood acute
      lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG
      randomized phase III trial 58951.
AB  - Asparaginase is an essential component of combination chemotherapy for childhood
      acute lymphoblastic leukemia and non-Hodgkin lymphoma. The value of asparaginase
      was further addressed in a group of non-very high-risk patients by comparing
      prolonged (long-asparaginase) versus standard (short-asparaginase) native E. coli
      asparaginase treatment in a randomized part of the phase III 58951 trial of the
      European Organization for Research and Treatment of Cancer Children's Leukemia
      Group. The main endpoint was disease-free survival. Overall, 1,552 patients were
      randomly assigned to long-asparaginase (775 patients) or short-asparaginase (777
      patients). Patients with grade >=2 allergy to native E. coli asparaginase were
      switched to equivalent doses of Erwinia or pegylated E. coli asparaginase. The 8
      year disease-free survival rate (+/-standard error) was 87.0+/-1.3% in the long
      asparaginase group and 84.4+/-1.4% in the short-asparaginase group (hazard ratio:
      0.87; P=0.33) and the 8-year overall survival rate was 92.6+/-1.0% and 91.3+/
      1.2% respectively (hazard ratio: 0.89; P=0.53). An exploratory analysis suggested
      that the impact of long-asparaginase was beneficial in the National Cancer
      Institute standard-risk group with regards to disease-free survival (hazard
      ratio: 0.70; P=0.057), but far less so with regards to overall survival (hazard
      ratio: 0.89). The incidences of grade 3-4 infection during consolidation (25.2%
      versus 14.4%) and late intensification (22.6% versus 15.9%) and the incidence of
      grade 2-4 allergy were higher in the long-asparaginase arm (30% versus 21%).
      Prolonged native E. coli asparaginase therapy in consolidation and late
      intensification for our non-very high-risk patients did not improve overall
      outcome but led to an increase in infections and allergy. This trial was
      registered at www.clinicaltrials.gov as #NCT00003728.

PMID- 28751567
TI  - The ADAMTS131239-1253 peptide is a dominant HLA-DR1-restricted CD4+ T-cell
      epitope.
AB  - Acquired thrombotic thrombocytopenic purpura is a rare and severe disease
      characterized by auto-antibodies directed against "A Disintegrin And
      Metalloproteinase with Thrombospondin type 1 repeats, 13th member" (ADAMTS13), a
      plasma protein involved in hemostasis. Involvement of CD4+ T cells in the
      pathogenesis of the disease is suggested by the IgG isotype of the antibodies.
      However, the nature of the CD4+ T-cell epitopes remains poorly characterized.
      Here, we determined the HLA-DR-restricted CD4+ T-cell epitopes of ADAMTS13.
      Candidate T-cell epitopes were predicted in silico and binding affinities were
      confirmed in competitive enzyme-linked immunosorbent assays. ADAMTS13-reactive
      CD4+ T-cell hybridomas were generated following immunization of HLA-DR1
      transgenic mice (Sure-L1 strain) and used to screen the candidate epitopes. We
      identified the ADAMTS131239-1253 peptide as the single immunodominant HLA-DR1
      restricted CD4+ T-cell epitope. This peptide is located in the CUB2 domain of
      ADAMTS13. It was processed by dendritic cells, stimulated CD4+ T cells from Sure
      L1 mice and was recognized by CD4+ T cells from an HLA-DR1-positive patient with
      acute thrombotic thrombocytopenic purpura. Interestingly, the ADAMTS131239-1253
      peptide demonstrated promiscuity towards HLA-DR11 and HLA-DR15. Our work paves
      the way towards the characterization of the ADAMTS13-specific CD4+ T-cell
      response in patients with thrombotic thrombocytopenic purpura using ADAMTS131239
      1253-loaded HLA-DR tetramers.

PMID- 28751568
TI  - mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling,
      Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient
      Mice.
AB  - OBJECTIVE: Elastin deficiency because of heterozygous loss of an ELN allele in
      Williams syndrome causes obstructive aortopathy characterized by medial
      thickening and fibrosis and consequent aortic stiffening. Previous work in Eln
      null mice with a severe arterial phenotype showed that inhibition of mTOR
      (mechanistic target of rapamycin), a key regulator of cell growth, lessened the
      aortic obstruction but did not prevent early postnatal death. We investigated the
      effects of mTOR inhibition in Eln-null mice partially rescued by human ELN that
      manifest a less severe arterial phenotype and survive long term. APPROACH AND
      RESULTS: Thoracic aortas of neonatal and juvenile mice with graded elastin
      deficiency exhibited increased signaling through both mTOR complex 1 and 2.
      Despite lower predicted wall stress, there was increased phosphorylation of focal
      adhesion kinase, suggestive of greater integrin activation, and increased
      transforming growth factor-beta-signaling mediators, associated with increased
      collagen expression. Pharmacological blockade of mTOR by rapalogs did not improve
      luminal stenosis but reduced mechanosignaling (in delayed fashion after mTOR
      complex 1 inhibition), medial collagen accumulation, and stiffening of the aorta.
      Rapalog administration also retarded somatic growth, however, and precipitated
      neonatal deaths. Complementary, less-toxic strategies to inhibit mTOR via altered
      growth factor and nutrient responses were not effective. CONCLUSIONS: In addition
      to previously demonstrated therapeutic benefits of rapalogs decreasing smooth
      muscle cell proliferation in the absence of elastin, we find that rapalogs also
      prevent aortic fibrosis and stiffening attributable to partial elastin
      deficiency. Our findings suggest that mTOR-sensitive perturbation of smooth
      muscle cell mechanosensing contributes to elastin aortopathy.

PMID- 28751569
TI  - CYLD Deubiquitinates Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4
      Contributing to Adventitial Remodeling.
AB  - OBJECTIVE: Transdifferentiation of adventitial fibroblasts (AFs) into
      myofibroblasts plays a critical role during the vascular remodeling that occurs
      during atherosclerosis, restenosis, and aortic aneurysm. The
      ubiquitination/deubiquitination regulatory system is essential for the quality
      control of proteins. The involvement of ubiquitination/deubiquitination during AF
      transdifferentiation remains largely unknown. In this study, we determined the
      role of cylindromatosis (CYLD), a deubiquitinase, in the process of AF
      differentiation and activation in vitro and in vivo. APPROACH AND RESULTS:
      Transforming growth factor-beta1 and homocysteine, 2 known inducers of AF
      transdifferentiation, greatly upregulated CYLD expression in a time- and dose
      dependent manner. The silencing of CYLD significantly inhibited AF
      transdifferentiation and activation as evidenced by the expression of contractile
      proteins, the production of the proinflammatory cytokines MCP-1 (monocyte
      chemotactic protein 1) and IL-6 (interleukin-6), the deposition of extracellular
      matrix, and cell migration. We further asked whether CYLD mediates AF activation
      via the regulation of nicotinamide adenine dinucleotide phosphate oxidase 4
      (Nox4) as it is an essential factor during AF transdifferentiation. Indeed, the
      silencing of CYLD repressed transforming growth factor-beta1-induced and
      homocysteine-induced Nox4 upregulation and reactive oxygen species production,
      whereas Nox4 overexpression greatly rescued the inhibitory effect on AF
      activation by CYLD silencing. Most interestingly, transforming growth factor
      beta1 and homocysteine repressed Nox4 ubiquitination and prolonged the half-life
      of Nox4. Moreover, Nox4 was deubiquitinated via a direct interaction with the
      ubiquitin-specific protease domain of CYLD. In accordance, hyperhomocysteinemia
      significantly increased adventitial CYLD and Nox4 expression, promoted AF
      transdifferentiation, and aggravated CaPO4-induced abdominal aortic aneurysm in
      mice. These effects were abolished in CYLD-/- mice. CONCLUSIONS: CYLD contributes
      to the transdifferentiation of AFs via deubiquitinating Nox4 and may play a role
      in vascular remodeling.

PMID- 28751570
TI  - Association of Coronary Perivascular Adipose Tissue Inflammation and Drug-Eluting
      Stent-Induced Coronary Hyperconstricting Responses in Pigs: 18F
      Fluorodeoxyglucose Positron Emission Tomography Imaging Study.
AB  - OBJECTIVE: Although coronary perivascular adipose tissue (PVAT) may play
      important roles as a source of inflammation, the association of coronary PVAT
      inflammation and coronary hyperconstricting responses remains to be examined. We
      addressed this important issue in a porcine model of coronary hyperconstricting
      responses after drug-eluting stent implantation with 18F-fluorodeoxyglucose (18F
      FDG) positron emission tomographic imaging. APPROACH AND RESULTS: An everolimus
      eluting stent (EES) was randomly implanted in pigs into the left anterior
      descending or the left circumflex coronary artery while nonstented coronary
      artery was used as a control. After 1 month, coronary vasoconstricting responses
      to intracoronary serotonin (10 and 100 MUg/kg) were examined by coronary
      angiography in vivo, followed by in vivo and ex vivo 18F-FDG positron emission
      tomographic/computed tomographic imaging. Coronary vasoconstricting responses to
      serotonin were significantly enhanced at the EES edges compared with the control
      site (P<0.01; n=40). Notably, in vivo and ex vivo 18F-FDG positron emission
      tomographic/computed tomographic imaging and autoradiography showed enhanced 18F
      FDG uptake and its accumulation in PVAT at the EES edges compared with the
      control site, respectively (both P<0.05). Furthermore, histological and reverse
      transcription polymerase chain reaction analysis showed that inflammatory changes
      of coronary PVAT were significantly enhanced at the EES edges compared with the
      control site (all P<0.01). Importantly, Rho-kinase expressions (ROCK1/ROCK2) and
      Rho-kinase activity (phosphorylated myosin phosphatase target subunit-1) at the
      EES edges were significantly enhanced compared with the control site.
      CONCLUSIONS: These results indicate for the first time that inflammatory changes
      of coronary PVAT are associated with drug-eluting stent-induced coronary
      hyperconstricting responses in pigs in vivo and that 18F-FDG positron emission
      tomographic imaging is useful for assessment of coronary PVAT inflammation.

PMID- 28751571
TI  - In Vivo Base Editing of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) as
      a Therapeutic Alternative to Genome Editing.
AB  - OBJECTIVE: High-efficiency genome editing to disrupt therapeutic target genes,
      such as PCSK9 (proprotein convertase subtilisin/kexin type 9), has been
      demonstrated in preclinical animal models, but there are safety concerns because
      of the unpredictable nature of cellular repair of double-strand breaks, as well
      as off-target mutagenesis. Moreover, precise knock-in of specific nucleotide
      changes-whether to introduce or to correct gene mutations-has proven to be
      inefficient in nonproliferating cells in vivo. Base editors comprising CRISPR
      Cas9 (clustered regularly interspaced short palindromic repeats [CRISPR]-CRISPR
      associated 9) fused to a cytosine deaminase domain can effect the alteration of
      cytosine bases to thymine bases in genomic DNA in a sequence-specific fashion,
      without the need for double-strand DNA breaks. The efficacy of base editing has
      not been established in vivo. The goal of this study was to assess whether in
      vivo base editing could be used to modify the mouse Pcsk9 gene in a sequence
      specific fashion in the liver in adult mice. APPROACH AND RESULTS: We screened
      base editors for activity in cultured cells, including human-induced pluripotent
      stem cells. We then delivered a base editor into the livers of adult mice to
      assess whether it could introduce site-specific nonsense mutations into the Pcsk9
      gene. In adult mice, this resulted in substantially reduced plasma PCSK9 protein
      levels (>50%), as well as reduced plasma cholesterol levels (~30%). There was no
      evidence of off-target mutagenesis, either cytosine-to-thymine edits or indels.
      CONCLUSIONS: These results demonstrate the ability to precisely introduce
      therapeutically relevant nucleotide variants into the genome in somatic tissues
      in adult mammals, as well as highlighting a potentially safer alternative to
      therapeutic genome editing.

PMID- 28751572
TI  - Short-Term Exposure to Ambient Air Pollution and Biomarkers of Systemic
      Inflammation: The Framingham Heart Study.
AB  - OBJECTIVE: The objective of this study is to examine associations between short
      term exposure to ambient air pollution and circulating biomarkers of systemic
      inflammation in participants from the Framingham Offspring and Third Generation
      cohorts in the greater Boston area. APPROACH AND RESULTS: We included 3996
      noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived
      within 50 km from a central air pollution monitoring site in Boston, MA, and
      calculated the 1- to 7-day moving averages of fine particulate matter
      (diameter<2.5 um), black carbon, sulfate, nitrogen oxides, and ozone before the
      examination visits. We used linear mixed effects models for C-reactive protein
      and tumor necrosis factor receptor 2, which were measured up to twice for each
      participant; we used linear regression models for interleukin-6, fibrinogen, and
      tumor necrosis factor alpha, which were measured once. We adjusted for
      demographics, socioeconomic position, lifestyle, time, and weather. The 3- to 7
      day moving averages of fine particulate matter (diameter<2.5 um) and sulfate were
      positively associated with C-reactive protein concentrations. A 5 ug/m3 higher 5
      day moving average fine particulate matter (diameter<2.5 um) was associated with
      4.2% (95% confidence interval: 0.8, 7.6) higher circulating C-reactive protein.
      Positive associations were also observed for nitrogen oxides with interleukin-6
      and for black carbon, sulfate, and ozone with tumor necrosis factor receptor 2.
      However, black carbon, sulfate, and nitrogen oxides were negatively associated
      with fibrinogen, and sulfate was negatively associated with tumor necrosis factor
      alpha. CONCLUSIONS: Higher short-term exposure to relatively low levels of
      ambient air pollution was associated with higher levels of C-reactive protein,
      interleukin-6, and tumor necrosis factor receptor 2 but not fibrinogen or tumor
      necrosis factor alpha in individuals residing in the greater Boston area.

PMID- 28751573
TI  - Sox10+ Cells Contribute to Vascular Development in Multiple Organs-Brief Report.
AB  - OBJECTIVE: Previous genetic lineage tracing studies showed that Sox10+ cells
      differentiate into vascular mural cells, limited to neural crest-derived blood
      vessels in craniofacial tissues, aortic arch, pulmonary arch arteries,
      brachiocephalic, carotid arteries, and thymus. The purpose of this study was to
      investigate the contribution of Sox10+ cells to the vascular development in other
      tissues and organs and their relationship with neural crest. APPROACH AND
      RESULTS: Using genetic lineage tracing technique based on Cre/LoxP system, we
      examined blood vessels in the adult organs of the mice expressing Sox10-Cre/Rosa
      LoxP-red fluorescent protein or Wnt1-Cre/Rosa-LoxP-red fluorescent protein by
      immunohistological analysis. In addition to previously reported tissues and
      organs derived from neural crest, we showed that Sox10+ cells also contributed to
      vascular mural cells in the lung, spleen, and kidney, which are derived from non
      neural crest origin as evidenced by red fluorescent protein-negative blood
      vessels in these 3 organs of Wnt1-Cre/Rosa-LoxP-red fluorescent protein mice.
      CONCLUSIONS: This study demonstrates that Sox10+ cells contribute to pericytes
      and smooth muscle cells in most parts of the body, including those from neural
      crest and non-neural crest, which has significant implications in vascular
      remodeling under physiological and pathological conditions.

PMID- 28751574
TI  - Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in
      Angiogenesis and Placenta Development.
AB  - OBJECTIVE: ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type
      1 repeats, member 13) is primarily synthesized in liver. The biosynthesis of
      ADAMTS13 and its physiological role in placenta are not known. APPROACH AND
      RESULTS: We used real-time polymerase chain reaction, immunohistochemistry, and
      Western blotting analyses, as well as proteolytic cleavage of FRETS (fluorescent
      resonance energy transfers)-VWF73, to determine ADAMTS13 expression in placenta
      and trophoblasts obtained from individuals with normal pregnancy and patients
      with severe preeclampsia. We also determined the role of ADAMTS13 in extravillous
      trophoblasts using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay, wound scratch assay, transwell migration assay, tube formation assay, and
      tissue outgrowth assays. We showed that full-length and proteolytically active
      ADAMTS13 was expressed in normal human placenta, primarily in the trophoblasts
      and villous core fetal vessel endothelium during pregnancy. Placental expression
      of ADAMTS13 mRNA, protein, and proteolytic activity was at the highest levels
      during the first trimester and significantly reduced at the term of gestation.
      Additionally, significantly reduced levels of placental ADAMTS13 expression was
      detected under hypoxic conditions and in patients with preeclampsia. In addition,
      recombinant ADAMTS13 protease stimulated proliferation, migration, invasion, and
      network formation of trophoblastic cells in culture. Finally, knockdown of
      ADAMTS13 expression attenuated the ability of tube formation in trophoblast (HTR
      8/SVNEO) cells and the extravillous trophoblast outgrowth in placental explants.
      CONCLUSIONS: Our results demonstrate for the first time the expression of
      ADAMTS13 mRNA and protein in normal and abnormal placental tissues and its role
      in promoting angiogenesis and trophoblastic cell development. The findings
      support the potential role of the ADAMTS13-von Willebrand factor pathway in
      normal pregnancy and pathogenesis of preeclampsia.

PMID- 28751575
TI  - Effects of Intranasal Insulin on Triglyceride-Rich Lipoprotein Particle
      Production in Healthy Men.
AB  - OBJECTIVE: Insulin administered directly into the brain acutely suppresses
      hepatic glucose production and triglyceride-rich lipoprotein (TRL) secretion in
      rodents. In addition, intranasally administered insulin, which selectively raises
      cerebrospinal fluid insulin concentration, suppresses hepatic glucose production
      in humans; however, its effect on TRL secretion in humans has not previously been
      examined. In this study, we examined whether intranasal insulin, administered at
      a dose that has previously been shown to suppress hepatic glucose production,
      modulates TRL particle secretion by the liver and intestine in humans. APPROACH
      AND RESULTS: Nine healthy, normolipidemic, and normoglycemic men participated in
      a study consisting of 2 randomized study arms. Subjects received intranasal
      lispro insulin (40 IU) or placebo. Because intranasal insulin results in a rapid
      and transient increase in systemic insulin concentration after administration, we
      matched systemic insulin concentrations in the 2 study arms by infusing lispro
      insulin intravenously for 30 minutes together with intranasal placebo
      administration. Apo (apolipoprotein) B100-containing (hepatically derived) and
      apoB48-containing (intestinally derived) TRL lipoprotein particle turnover were
      measured for the ensuing 10 hours under pancreatic clamp conditions and constant
      fed state, using stable isotope enrichment techniques and multicompartmental
      modeling. Under these experimental conditions, no significant effects of
      intranasal insulin versus placebo on TRL apoB100 or B48 concentrations,
      fractional catabolic rates, or production rates were observed. CONCLUSIONS:
      Insulin delivered intranasally at a dose that has been shown to raise
      cerebrospinal fluid insulin concentration and suppress hepatic glucose production
      does not affect TRL particle production by the liver and intestine in healthy
      men. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT03141827.

PMID- 28751576
TI  - Analytic Considerations for Repeated Measures of eGFR in Cohort Studies of CKD.
AB  - Repeated measures of various biomarkers provide opportunities for us to enhance
      understanding of many important clinical aspects of CKD, including patterns of
      disease progression, rates of kidney function decline under different risk
      factors, and the degree of heterogeneity in disease manifestations across
      patients. However, because of unique features, such as correlations across visits
      and time dependency, these data must be appropriately handled using longitudinal
      data analysis methods. We provide a general overview of the characteristics of
      data collected in cohort studies and compare appropriate statistical methods for
      the analysis of longitudinal exposures and outcomes. We use examples from the
      Chronic Renal Insufficiency Cohort Study to illustrate these methods. More
      specifically, we model longitudinal kidney outcomes over annual clinical visits
      and assess the association with both baseline and longitudinal risk factors.

PMID- 28751577
TI  - Outcomes of Deceased Donor Kidney Offers to Patients at the Top of the Waiting
      List.
AB  - BACKGROUND AND OBJECTIVES: Transplant centers may accept or refuse deceased-donor
      kidneys that are offered to their patients at the top of the waiting list. We
      sought to determine the outcomes of deceased-donor kidney offers and their
      association with characteristics of waitlisted patients and organ donors. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: We examined all 7 million deceased-donor
      adult kidney offers in the United States from 2007 to 2012 that led to eventual
      transplantation. Data were obtained from the national organ allocation system
      through the United Network of Organ Sharing. The study cohort consisted of
      178,625 patients waitlisted for a deceased-donor kidney transplant and 31,230
      deceased donors. We evaluated offers made to waitlisted patients and their
      outcomes (transplantation or specific reason for refusal). RESULTS: Deceased
      donor kidneys were offered a median of seven times before being accepted for
      transplantation. The most common reasons for refusal of an offer were donor
      related factors, e.g., age or organ quality (3.2 million offers, 45.0%), and
      transplant center bypass, e.g., minimal acceptance criteria not met (3.2 million
      offers, 44.0%). After adjustment for characteristics of waitlisted patients,
      organ donors, and transplant centers, male (odds ratio [OR], 0.93; 95% confidence
      interval [95% CI], 0.91 to 0.95) and Hispanic (OR, 0.96; 95% CI, 0.93 to 0.99)
      waitlisted patients were less likely to have an offer accepted than female and
      white patients, respectively. The likelihood of offer acceptance varied greatly
      across transplant centers (interquartile ratio, 2.28). CONCLUSIONS: Transplant
      centers frequently refuse deceased-donor kidneys. Such refusals differ by patient
      and donor characteristics, may contribute to disparities in access to
      transplantation, and vary greatly across transplant centers.

PMID- 28751578
TI  - Achieving Equity through Reducing Variability in Accepting Deceased Donor Kidney
      Offers.

PMID- 28751579
TI  - Promoterless gene targeting without nucleases rescues lethality of a Crigler
      Najjar syndrome mouse model.
AB  - Crigler-Najjar syndrome type I (CNSI) is a rare monogenic disease characterized
      by severe neonatal unconjugated hyperbilirubinemia with a lifelong risk of
      neurological damage and death. Liver transplantation is the only curative option,
      which has several limitations and risks. We applied an in vivo gene targeting
      approach based on the insertion, without the use of nucleases, of a promoterless
      therapeutic cDNA into the albumin locus of a mouse model reproducing all major
      features of CNSI Neonatal transduction with the donor vector resulted in the
      complete rescue from neonatal lethality, with a therapeutic reduction in plasma
      bilirubin lasting for at least 12 months, the latest time point analyzed. Mutant
      mice, which expressed about 5-6% of WT Ugt1a1 levels, showed normal liver
      histology and motor-coordination abilities, suggesting no functional liver or
      brain abnormalities. These results proved that the promoterless gene therapy is
      applicable for CNSI, providing therapeutic levels of an intracellular ER membrane
      bound enzyme responsible for a lethal liver metabolic disease.

PMID- 28751580
TI  - Intracellular adenosine regulates epigenetic programming in endothelial cells to
      promote angiogenesis.
AB  - The nucleoside adenosine is a potent regulator of vascular homeostasis, but it
      remains unclear how expression or function of the adenosine-metabolizing enzyme
      adenosine kinase (ADK) and the intracellular adenosine levels influence
      angiogenesis. We show here that hypoxia lowered the expression of ADK and
      increased the levels of intracellular adenosine in human endothelial cells.
      Knockdown (KD) of ADK elevated intracellular adenosine, promoted proliferation,
      migration, and angiogenic sprouting in human endothelial cells. Additionally,
      mice deficient in endothelial ADK displayed increased angiogenesis as evidenced
      by the rapid development of the retinal and hindbrain vasculature, increased
      healing of skin wounds, and prompt recovery of arterial blood flow in the
      ischemic hindlimb. Mechanistically, hypomethylation of the promoters of a series
      of pro-angiogenic genes, especially for VEGFR2 in ADK KD cells, was demonstrated
      by the Infinium methylation assay. Methylation-specific PCR, bisulfite
      sequencing, and methylated DNA immunoprecipitation further confirmed
      hypomethylation in the promoter region of VEGFR2 in ADK-deficient endothelial
      cells. Accordingly, loss or inactivation of ADK increased VEGFR2 expression and
      signaling in endothelial cells. Based on these findings, we propose that ADK
      downregulation-induced elevation of intracellular adenosine levels in endothelial
      cells in the setting of hypoxia is one of the crucial intrinsic mechanisms that
      promote angiogenesis.

PMID- 28751581
TI  - Going viral? Linking the etiology of human prostate cancer to the PCA3 long
      noncoding RNA and oncogenic viruses.

PMID- 28751583
TI  - Cover stories: A method for revealing chromatin.

PMID- 28751582
TI  - ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and
      mitotic cells.
AB  - The chromatin structure of DNA determines genome compaction and activity in the
      nucleus. On the basis of in vitro structures and electron microscopy (EM)
      studies, the hierarchical model is that 11-nanometer DNA-nucleosome polymers fold
      into 30- and subsequently into 120- and 300- to 700-nanometer fibers and mitotic
      chromosomes. To visualize chromatin in situ, we identified a fluorescent dye that
      stains DNA with an osmiophilic polymer and selectively enhances its contrast in
      EM. Using ChromEMT (ChromEM tomography), we reveal the ultrastructure and three
      dimensional (3D) organization of individual chromatin polymers, megabase domains,
      and mitotic chromosomes. We show that chromatin is a disordered 5- to 24
      nanometer-diameter curvilinear chain that is packed together at different 3D
      concentration distributions in interphase and mitosis. Chromatin chains have many
      different particle arrangements and bend at various lengths to achieve structural
      compaction and high packing densities.

PMID- 28751585
TI  - News at a glance.

PMID- 28751584
TI  - Kynurenines: Tryptophan's metabolites in exercise, inflammation, and mental
      health.
AB  - Kynurenine metabolites are generated by tryptophan catabolism and regulate
      biological processes that include host-microbiome signaling, immune cell
      response, and neuronal excitability. Enzymes of the kynurenine pathway are
      expressed in different tissues and cell types throughout the body and are
      regulated by cues, including nutritional and inflammatory signals. As a
      consequence of this systemic metabolic integration, peripheral inflammation can
      contribute to accumulation of kynurenine in the brain, which has been associated
      with depression and schizophrenia. Conversely, kynurenine accumulation can be
      suppressed by activating kynurenine clearance in exercised skeletal muscle. The
      effect of exercise training on depression through modulation of the kynurenine
      pathway highlights an important mechanism of interorgan cross-talk mediated by
      these metabolites. Here, we discuss peripheral mechanisms of tryptophan
      kynurenine metabolism and their effects on inflammatory, metabolic, oncologic,
      and psychiatric disorders.

PMID- 28751586
TI  - Turmoil imperils research university in Andes.

PMID- 28751587
TI  - Head of France's main funding body resigns amid acrimony.

PMID- 28751588
TI  - Travel ban would slam university in North Korea.

PMID- 28751589
TI  - Funders groan under growing review burden.

PMID- 28751590
TI  - Disease sleuths unmask deadly encephalitis culprit.

PMID- 28751591
TI  - 'Scientific wellness' study divides researchers.

PMID- 28751592
TI  - Biology of the Book.

PMID- 28751593
TI  - Nitrogen stewardship in the Anthropocene.

PMID- 28751594
TI  - Directing reconfigurable DNA nanoarrays.

PMID- 28751595
TI  - Photolithography based on nanocrystals.

PMID- 28751596
TI  - The genome-seeing it clearly now.

PMID- 28751597
TI  - Genetic biomarker for cancer immunotherapy.

PMID- 28751598
TI  - Improving global integration of crop research.

PMID- 28751599
TI  - Contingent valuation: Flawed logic?

PMID- 28751600
TI  - Contingent valuation: Flawed logic?-Response.

PMID- 28751601
TI  - Call to restore NIH's cap on grant funding.

PMID- 28751602
TI  - Second-scale nuclear spin coherence time of ultracold 23Na40K molecules.
AB  - Coherence, the stability of the relative phase between quantum states, is central
      to quantum mechanics and its applications. For ultracold dipolar molecules at sub
      microkelvin temperatures, internal states with robust coherence are predicted to
      offer rich prospects for quantum many-body physics and quantum information
      processing. We report the observation of stable coherence between nuclear spin
      states of ultracold fermionic sodium-potassium (NaK) molecules in the singlet
      rovibrational ground state. Ramsey spectroscopy reveals coherence times on the
      scale of 1 second; this enables high-resolution spectroscopy of the molecular
      gas. Collisional shifts are shown to be absent down to the 100-millihertz level.
      This work opens the door to the use of molecules as a versatile quantum memory
      and for precision measurements on dipolar quantum matter.

PMID- 28751603
TI  - Spectral narrowing of x-ray pulses for precision spectroscopy with nuclear
      resonances.
AB  - Spectroscopy of nuclear resonances offers a wide range of applications due to the
      remarkable energy resolution afforded by their narrow linewidths. However,
      progress toward higher resolution is inhibited at modern x-ray sources because
      they deliver only a tiny fraction of the photons on resonance, with the remainder
      contributing to an off-resonant background. We devised an experimental setup that
      uses the fast mechanical motion of a resonant target to manipulate the spectrum
      of a given x-ray pulse and to redistribute off-resonant spectral intensity onto
      the resonance. As a consequence, the resonant pulse brilliance is increased while
      the off-resonant background is reduced. Because our method is compatible with
      existing and upcoming pulsed x-ray sources, we anticipate that this approach will
      find applications that require ultranarrow x-ray resonances.

PMID- 28751604
TI  - Tough adhesives for diverse wet surfaces.
AB  - Adhesion to wet and dynamic surfaces, including biological tissues, is important
      in many fields but has proven to be extremely challenging. Existing adhesives are
      cytotoxic, adhere weakly to tissues, or cannot be used in wet environments. We
      report a bioinspired design for adhesives consisting of two layers: an adhesive
      surface and a dissipative matrix. The former adheres to the substrate by
      electrostatic interactions, covalent bonds, and physical interpenetration. The
      latter amplifies energy dissipation through hysteresis. The two layers
      synergistically lead to higher adhesion energies on wet surfaces as compared with
      those of existing adhesives. Adhesion occurs within minutes, independent of blood
      exposure and compatible with in vivo dynamic movements. This family of adhesives
      may be useful in many areas of application, including tissue adhesives, wound
      dressings, and tissue repair.

PMID- 28751605
TI  - Synthesis of FeH5: A layered structure with atomic hydrogen slabs.
AB  - High pressure promotes the formation of polyhydrides with unusually high hydrogen
      to-metal ratios. These polyhydrides have complex hydrogenic sublattices. We
      synthesized iron pentahydride (FeH5) by a direct reaction between iron and H2
      above 130 gigapascals in a laser-heated diamond anvil cell. FeH5 exhibits a
      structure built of atomic hydrogen only. It consists of intercalated layers of
      quasicubic FeH3 units and four-plane slabs of thin atomic hydrogen. The
      distribution of the valence electron density indicates a bonding between hydrogen
      and iron atoms but none between hydrogen atoms, presenting a two-dimensional
      metallic character. The discovery of FeH5 suggests a low-pressure path to make
      materials that approach bulk dense atomic hydrogen.

PMID- 28751606
TI  - Direct optical lithography of functional inorganic nanomaterials.
AB  - Photolithography is an important manufacturing process that relies on using
      photoresists, typically polymer formulations, that change solubility when
      illuminated with ultraviolet light. Here, we introduce a general chemical
      approach for photoresist-free, direct optical lithography of functional inorganic
      nanomaterials. The patterned materials can be metals, semiconductors, oxides,
      magnetic, or rare earth compositions. No organic impurities are present in the
      patterned layers, which helps achieve good electronic and optical properties. The
      conductivity, carrier mobility, dielectric, and luminescence properties of
      optically patterned layers are on par with the properties of state-of-the-art
      solution-processed materials. The ability to directly pattern all-inorganic
      layers by using a light exposure dose comparable with that of organic
      photoresists provides an alternate route for thin-film device manufacturing.

PMID- 28751607
TI  - Seismic evidence for partial melting at the root of major hot spot plumes.
AB  - Ultralow-velocity zones are localized regions of extreme material properties
      detected seismologically at the base of Earth's mantle. Their nature and role in
      mantle dynamics are poorly understood. We used shear waves diffracted at the core
      mantle boundary to illuminate the root of the Iceland plume from different
      directions. Through waveform modeling, we detected a large ultralow-velocity zone
      and constrained its shape to be axisymmetric to a very good first order. We thus
      attribute it to partial melting of a locally thickened, denser- and hotter-than
      average layer, reflecting dynamics and elevated temperatures within the plume
      root. Such structures are few and far apart, and they may be characteristic of
      the roots of some of the broad mantle plumes tomographically imaged within the
      large low-shear-velocity provinces in the lower mantle.

PMID- 28751608
TI  - Nanocrystalline copper films are never flat.
AB  - We used scanning tunneling microscopy to study low-angle grain boundaries at the
      surface of nearly planar copper nanocrystalline (111) films. The presence of
      grain boundaries and their emergence at the film surface create valleys composed
      of dissociated edge dislocations and ridges where partial dislocations have
      recombined. Geometric analysis and simulations indicated that valleys and ridges
      were created by an out-of-plane grain rotation driven by reduction of grain
      boundary energy. These results suggest that in general, it is impossible to form
      flat two-dimensional nanocrystalline films of copper and other metals exhibiting
      small stacking fault energies and/or large elastic anisotropy, which induce a
      large anisotropy in the dislocation-line energy.

PMID- 28751610
TI  - Eutrophication will increase during the 21st century as a result of precipitation
      changes.
AB  - Eutrophication, or excessive nutrient enrichment, threatens water resources
      across the globe. We show that climate change-induced precipitation changes alone
      will substantially increase (19 +/- 14%) riverine total nitrogen loading within
      the continental United States by the end of the century for the "business-as
      usual" scenario. The impacts, driven by projected increases in both total and
      extreme precipitation, will be especially strong for the Northeast and the corn
      belt of the United States. Offsetting this increase would require a 33 +/- 24%
      reduction in nitrogen inputs, representing a massive management challenge.
      Globally, changes in precipitation are especially likely to also exacerbate
      eutrophication in India, China, and Southeast Asia. It is therefore imperative
      that water quality management strategies account for the impact of projected
      future changes in precipitation on nitrogen loading.

PMID- 28751609
TI  - Control of species-dependent cortico-motoneuronal connections underlying manual
      dexterity.
AB  - Superior manual dexterity in higher primates emerged together with the appearance
      of cortico-motoneuronal (CM) connections during the evolution of the mammalian
      corticospinal (CS) system. Previously thought to be specific to higher primates,
      we identified transient CM connections in early postnatal mice, which are
      eventually eliminated by Sema6D-PlexA1 signaling. PlexA1 mutant mice maintain CM
      connections into adulthood and exhibit superior manual dexterity as compared with
      that of controls. Last, differing PlexA1 expression in layer 5 of the motor
      cortex, which is strong in wild-type mice but weak in humans, may be explained by
      FEZF2-mediated cis-regulatory elements that are found only in higher primates.
      Thus, species-dependent regulation of PlexA1 expression may have been crucial in
      the evolution of mammalian CS systems that improved fine motor control in higher
      primates.

PMID- 28751611
TI  - CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent
      polypeptides.
AB  - Ribosome stalling leads to recruitment of the ribosome quality control complex
      (RQC), which targets the partially synthesized polypeptide for proteasomal
      degradation through the action of the ubiquitin ligase Ltn1p. A second core RQC
      component, Rqc2p, modifies the nascent polypeptide by adding a carboxyl-terminal
      alanine and threonine (CAT) tail through a noncanonical elongation reaction. Here
      we examined the role of CAT-tailing in nascent-chain degradation in budding
      yeast. We found that Ltn1p efficiently accessed only nascent-chain lysines
      immediately proximal to the ribosome exit tunnel. For substrates without Ltn1p
      accessible lysines, CAT-tailing enabled degradation by exposing lysines
      sequestered in the ribosome exit tunnel. Thus, CAT-tails do not serve as a
      degron, but rather provide a fail-safe mechanism that expands the range of RQC
      degradable substrates.

PMID- 28751612
TI  - From abalone to advocacy.

PMID- 28751613
TI  - Research Priorities in Sudden Unexpected Infant Death: An International
      Consensus.
AB  - Despite the success of safe sleep campaigns and the progress in understanding
      risk factors, the rate of reduction in the cases of sudden infant death syndrome
      has now slowed and it remains a leading cause of postneonatal mortality in many
      developed countries. Strategic action is needed to tackle this problem and it is
      now vital to identify how the sudden infant death research community may best
      target its efforts. The Global Action and Prioritization of Sudden Infant Death
      Project was an international consensus process that aimed to define and direct
      future research by investigating the priorities of expert and lay members of the
      sudden unexpected infant death (SUID) community across countries. The aim was to
      identify which areas of research should be prioritized to reduce the number of
      SUID deaths globally. Scientific researchers, clinicians, counselors, educators,
      and SUID parents from 25 countries took part across 2 online surveys to identify
      potential research priorities. Workshops subsequently took place in the United
      Kingdom, United States, and Australia to reach consensus and 10 priority areas
      for research were established. Three main themes among the priorities emerged:
      (1) a better understanding of mechanisms underlying SUID, (2) ensuring best
      practice in data collection, management and sharing, and (3) a better
      understanding of target populations and more effective communication of risk.
      SUID is a global problem and this project provides the international SUID
      community with a list of shared research priorities to more effectively work
      toward explaining and reducing the number of sudden infant deaths.

PMID- 28751614
TI  - Variations in Definitions and Outcome Measures in Gastroesophageal Reflux
      Disease: A Systematic Review.
AB  - CONTEXT: Gastroesophageal reflux (GER) is defined as GER disease (GERD) when it
      leads to troublesome symptoms and/or complications. We hypothesized that
      definitions and outcome measures in randomized controlled trials (RCTs) on
      pediatric GERD would be heterogeneous. OBJECTIVES: Systematically assess
      definitions and outcome measures in RCTs in this population. DATA SOURCES: Data
      were obtained through Cochrane, Embase, Medline, and Pubmed databases. STUDY
      SELECTION: We selected English-written therapeutic RCTs concerning GERD in
      children 0 to 18 years old. DATA EXTRACTION: Data were tabulated and presented
      descriptively. Each individual parameter or set of parameters with unique
      criteria for interpretation was considered a single definition for GER(D).
      Quality was assessed by using the Delphi score. RESULTS: A total of 2410 unique
      articles were found; 46 articles were included. Twenty-six (57%) studies defined
      GER by using 25 different definitions and investigated 25 different
      interventions. GERD was defined in 21 (46%) studies, all using a unique
      definition and investigating a total of 23 interventions. Respectively 87 and 61
      different primary outcome measures were reported by the studies in GER and GERD.
      Eight (17%) studies did not report on side effects. Of the remaining 38 (83%)
      studies that did report on side effects, 18 (47%) included this as predefined
      outcome measure of which 4 (22%) as a primary outcome measure. Sixteen studies
      (35%) were of good methodological quality. LIMITATIONS: Only English-written
      studies were included. CONCLUSIONS: Inconsistency and heterogeneity exist in
      definitions and outcome measures used in RCTs on pediatric GER and GERD;
      therefore, we recommend the development of a core outcome set.

PMID- 28751630
TI  - The Effect of SIN1 and Microtubules on Insulin Induced PKC zeta Activation.
AB  - BACKGROUND Protein kinase C zeta (PKC zeta) plays an important role in insulin
      induced glycometabolism and insulin receptor (IR) associated signaling pathways.
      The full activation of PKC zeta depends on its translocation from cytosol to
      membrane and phosphorylation at Thr410. However, the mechanism of PKC zeta
      activation remains elusive. In this study, the effect of SIN1 and microtubules on
      insulin-induced PKC zeta activation was investigated. MATERIAL AND METHODS HepG2
      cells were stimulated with insulin for co-immunoprecipitation (co-IP) assay. The
      immunocomplex was captured by using anti-PKC zeta, anti-SIN1 or anti-FLAG
      antibodies and was subjected to western blotting analysis for detecting PKC zeta,
      SIN1, and beta-tubulin protein expression level. The cells were intervened by
      small interfering RNA (siRNA) that targeted exon regions of SIN1. Then the
      glucose uptake ratio after cells were stimulated by insulin was measured. The PKC
      zeta insulin receptor levels in the membranes were analyzed. Cells stained with
      anti-PKC zeta, anti-SIN1 antibodies and probed with molecular probes were
      observed by immunofluorescence confocal microscopy. RESULTS SIN1 interacted and
      co-located with PKC zeta by pleckstrin homology (PH) domain. Downregulation of
      SIN1 severely impaired PKC zeta translocation and phosphorylation induced by
      insulin. PKC zeta co-immunoprecipitated with beta-tubulin at different intervals
      upon insulin stimulus, and the activation of PKC zeta was affected by paclitaxel
      and nocodazole. CONCLUSIONS PKC zeta translocated from cytosol to membrane
      depending on SIN1, which suggested that PKC zeta may be activated directly by
      PI3K and the reaction probably carried out on microtubules in HepG2 cells.

PMID- 28751631
TI  - Medication as a Cause of Acute Pancreatitis.
AB  - BACKGROUND Acute pancreatitis is an inflammatory condition of the pancreas
      characterized clinically by epigastric abdominal pain and elevated levels of
      pancreatic enzymes in the blood. Drug-induced pancreatitis has recently gained
      more attention and as a result, physicians are screening more frequently for
      medications as a cause of acute pancreatitis. CASE REPORT We report the case of a
      74-year-old man with a significant past medical history for coronary artery
      disease, sleep apnea, and gastroesophageal reflux disease who presented with
      epigastric pain radiating to the back. After a careful history was taken, it was
      found the patient recently started furosemide; therefore, a diagnosis of
      furosemide-induced acute pancreatitis was made. CONCLUSIONS Furosemide and other
      medications should be strongly considered in the differential diagnosis of
      patients presenting with acute pancreatitis.

PMID- 28751632
TI  - Extracorporeal Membrane Oxygenation Support for Rituximab-Induced Acute
      Respiratory Distress Syndrome in an ABO-Incompatible Living Donor Liver
      Transplant Recipient: Successful Management of a Rare Complication and a Review
      of the Literature.
AB  - BACKGROUND Rituximab is commonly used to reduce the agglutinin titer in ABO
      incompatible liver transplant recipients. Although well-tolerated, rituximab
      infusion therapy may result in severe pulmonary adverse effects such as drug
      induced pneumonitis, leading to acute respiratory distress syndrome (ARDS), which
      has a high mortality rate. Management of such rare cases in an ABO-incompatible
      patient has never been described before. Herein, we present successful use of
      extracorporeal membrane oxygenation (ECMO) support for rituximab-induced ARDS in
      an ABO-incompatible living donor liver transplantation (LDLT) recipient. CASE
      REPORT A 57-year-old man patient presented with acute-on-chronic hepatic failure.
      Due to worsening clinical condition and unavailability of a deceased donor organ,
      ABO-incompatible LDLT was considered. The patient received rituximab therapy and
      plasmapheresis 1 week before the transplantation to reduce the B cell count.
      However, he suddenly developed acute respiratory distress-like symptoms, with a
      chest X-ray suggesting organized pneumonia. Infectious etiology was excluded as
      evidenced from negative sputum and blood culture, which were repeated after 48 h.
      LDLT was performed and ECMO support was instituted in the immediate postoperative
      period due to worsening of the ARDS. The pulmonary signs improved, with a chest X
      ray showing clear lung fields on the 5th postoperative day. The patient recovered
      well and was discharged with normal liver functions in the 4th postoperative
      month. CONCLUSIONS This is first reported experience of successful use of ECMO in
      an ABO-incompatible liver transplant recipient with rituximab-induced ARDS. This
      experience shows the feasibility and effectiveness of ECMO support in liver
      transplant recipients with poor respiratory functions.

PMID- 28751633
TI  - Chemical characterization of the adhesive secretions of the salamander Plethodon
      shermani (Caudata, Plethodontidae).
AB  - Salamanders have developed a wide variety of antipredator mechanisms, including
      tail autotomy, colour patterns, and noxious skin secretions. As an addition to
      these tactics, the red-legged salamander (Plethodon shermani) uses adhesive
      secretions as part of its defensive strategy. The high bonding strength, the fast
      curing nature, and the composition of the biobased materials makes salamander
      adhesives interesting for practical applications in the medical sector. To
      understand the adhesive secretions of P. shermani, its components were chemically
      analysed by energy dispersive X-ray spectroscopy (EDX), inductively coupled
      plasma mass spectrometry (ICP-MS), amino acid analysis, and spectroscopy (ATR-IR,
      Raman). In addition, proteins were separated by gel-electrophoresis and selected
      spots were characterised by peptide mass fingerprinting. The salamander secretion
      contains a high amount of water and predominantly proteins (around 77% in the dry
      stage). The gel-electrophoresis and peptide mass fingerprint analyses revealed a
      de novo set of peptides/proteins, largely with a pI between 5.0 and 8.0 and a
      molecular mass distribution between 10 and 170 kDa. Only low homologies with
      other proteins present in known databases could be identified. The results
      indicate that the secretions of the salamander Plethodon clearly differ
      chemically from those shown for other glue-producing terrestrial or marine
      species and thus represent a unique glue system.

PMID- 28751634
TI  - Global biogeography, cryptic species and systematic issues in the shrimp genus
      Hippolyte Leach, 1814 (Decapoda: Caridea: Hippolytidae) by multimarker analyses.
AB  - Hippolyte is a genus of small bodied marine shrimps, with a global distribution.
      Here, we studied the phylogenetic and biogeographic relationships amongst the
      species of this genus with two mitochondrial and two nuclear markers, using
      Bayesian Inference, Maximum Likelihood, genetic divergence, molecular clock and S
      DIVA. In addition, the Indo-West Pacific genus Alcyonohippolyte was included.
      Based on sequences from 57 specimens of 27 species, we recovered a robust
      biogeographic scenario that shows the Indo-West Pacific as the probable ancestral
      area of the genus Hippolyte, which emerged in the Paleocene, followed by
      dispersal in three general directions: (1) South Pacific, (2) eastern Atlantic
      and Mediterranean Sea and (3) Americas, the latter with a primary colonization in
      the eastern Pacific followed by a radiation into the western Atlantic. Our
      analysis reveals that the species of the H. ventricosa group do not constitute a
      monophyletic group and Alcyonohippolyte does not constitute a reciprocally
      monophyletic group to Hippolyte, with both genera herein synonimised. The
      relationships and systematic status of several transisthmian and Atlantic species
      are clarified.

PMID- 28751635
TI  - Microfluidic Cell Retention Device for Perfusion of Mammalian Suspension Culture.
AB  - Continuous production of biologics, a growing trend in the biopharmaceutical
      industry, requires a reliable and efficient cell retention device that also
      maintains cell viability. Current filtration methods, such as tangential flow
      filtration using hollow-fiber membranes, suffer from membrane fouling, leading to
      significant reliability and productivity issues such as low cell viability,
      product retention, and an increased contamination risk associated with filter
      replacement. We introduce a novel cell retention device based on inertial sorting
      for perfusion culture of suspended mammalian cells. The device was characterized
      in terms of cell retention capacity, biocompatibility, scalability, and long-term
      reliability. This technology was demonstrated using a high concentration (>20
      million cells/mL) perfusion culture of an IgG1-producing Chinese hamster ovary
      (CHO) cell line for 18-25 days. The device demonstrated reliable and clog-free
      cell retention, high IgG1 recovery (>99%) and cell viability (>97%). Lab-scale
      perfusion cultures (350 mL) were used to demonstrate the technology, which can be
      scaled-out with parallel devices to enable larger scale operation. The new cell
      retention device is thus ideal for rapid perfusion process development in a
      biomanufacturing workflow.

PMID- 28751636
TI  - Increased functional connectivity after stroke correlates with behavioral scores
      in non-human primate model.
AB  - Here we characterized the functional connectivity (FC) changes occurring after a
      controlled MCA stroke in a primate model. We hypothesize that if FC can inform
      about the neural changes after a stroke in the non-human primate (NHP) stroke
      model, then significant FC changes after the stroke would have to correlate with
      the remaining behavioral capacities. Eleven cynomolgus monkeys underwent an
      experimental middle cerebral artery occlusion while five monkeys remained as the
      control group. One month later the neurological function was assessed with a set
      of fine motor tasks and the Nonhuman Primate Stroke Scale (NHPSS). Structural and
      functional connectivity analyses were done to compare both groups. Three FC
      changes showed significant behavioral correlations: right sensorimotor-right
      lateral intraparietal FC with the six-well task; left posterior intraparietal
      left dorsal premotor FC with the hill task; and right visual-left primary motor
      FC with the NHPSS. In the three instances, stronger FC correlated with better
      behavioral outcome. The results show that the functional changes correlating with
      behavioral outcomes involved sensorimotor cortices that were not restricted to
      the affected hemisphere. These results show that the FC analysis in NHP stroke
      model is a relevant methodology suitable to inform the neural changes occurring
      after a stroke.

PMID- 28751637
TI  - Sugar intake from sweet food and beverages, common mental disorder and
      depression: prospective findings from the Whitehall II study.
AB  - Intake of sweet food, beverages and added sugars has been linked with depressive
      symptoms in several populations. Aim of this study was to investigate
      systematically cross-sectional and prospective associations between sweet
      food/beverage intake, common mental disorder (CMD) and depression and to examine
      the role of reverse causation (influence of mood on intake) as potential
      explanation for the observed linkage. We analysed repeated measures (23,245
      person-observations) from the Whitehall II study using random effects regression.
      Diet was assessed using food frequency questionnaires, mood using validated
      questionnaires. Cross-sectional analyses showed positive associations. In
      prospective analyses, men in the highest tertile of sugar intake from sweet
      food/beverages had a 23% increased odds of incident CMD after 5 years (95% CI:
      1.02, 1.48) independent of health behaviours, socio-demographic and diet-related
      factors, adiposity and other diseases. The odds of recurrent depression were
      increased in the highest tertile for both sexes, but not statistically
      significant when diet-related factors were included in the model (OR 1.47; 95%
      CI: 0.98, 2.22). Neither CMD nor depression predicted intake changes. Our
      research confirms an adverse effect of sugar intake from sweet food/beverage on
      long-term psychological health and suggests that lower intake of sugar may be
      associated with better psychological health.

PMID- 28751638
TI  - Targeted DNA methylation in human cells using engineered dCas9
      methyltransferases.
AB  - Mammalian genomes exhibit complex patterns of gene expression regulated, in part,
      by DNA methylation. The advent of engineered DNA methyltransferases (MTases) to
      target DNA methylation to specific sites in the genome will accelerate many areas
      of biological research. However, targeted MTases require clear design rules to
      direct site-specific DNA methylation and minimize the unintended effects of off
      target DNA methylation. Here we report a targeted MTase composed of an
      artificially split CpG MTase (sMTase) with one fragment fused to a catalytically
      inactive Cas9 (dCas9) that directs the functional assembly of sMTase fragments at
      the targeted CpG site. We precisely map RNA-programmed DNA methylation to
      targeted CpG sites as a function of distance and orientation from the protospacer
      adjacent motif (PAM). Expression of the dCas9-sMTase in mammalian cells led to
      predictable and efficient (up to ~70%) DNA methylation at targeted sites.
      Multiplexing sgRNAs enabled targeting methylation to multiple sites in a single
      promoter and to multiple sites in multiple promoters. This programmable de novo
      MTase tool might be used for studying mechanisms of initiation, spreading and
      inheritance of DNA methylation, and for therapeutic gene silencing.

PMID- 28751639
TI  - High-performance nanoscale topological energy transduction.
AB  - The realization of high-performance, small-footprint, on-chip inductors remains a
      challenge in radio-frequency and power microelectronics, where they perform vital
      energy transduction in filters and power converters. Modern planar inductors
      consist of metallic spirals that consume significant chip area, resulting in low
      inductance densities. We present a novel method for magnetic energy transduction
      that utilizes ferromagnetic islands (FIs) on the surface of a 3D time-reversal
      invariant topological insulator (TI) to produce paradigmatically different
      inductors. Depending on the chemical potential, the FIs induce either an
      anomalous or quantum anomalous Hall effect in the topological surface states.
      These Hall effects direct current around the FIs, concentrating magnetic flux and
      producing a highly inductive device. Using a novel self-consistent simulation
      that couples AC non-equilibrium Green functions to fully electrodynamic solutions
      of Maxwell's equations, we demonstrate excellent inductance densities up to
      terahertz frequencies, thus harnessing the unique properties of topological
      materials for practical device applications.

PMID- 28751640
TI  - Large nonlinear dielectric behavior in BaTi1-xSnxO3.
AB  - BaTi1-xSnxO3 (BTSn, 0 <= x <= 0.30) ceramics were prepared by both the
      conventional sintering (CS) and sparking plasma sintering (SPS). Composition,
      temperature and grain size dependences of the nonlinear dielectric behaviors were
      systematically studied. BTSn was found to have especially large tunability
      (>=90%), which is larger than most other Pb-free systems, and is comparable to Pb
      based relaxors. The high dielectric tunability in BTSn is attributed to its
      specific domain structures. Besides, temperature dependent tunability of BTSn
      presents a dispersed behavior and the dispersion is enhanced with the increase of
      Sn4+ concentrations, which is explained by the compositional fluctuation model.

PMID- 28751641
TI  - Mass-spectrometry analysis of modifications at DNA termini induced by DNA
      polymerases.
AB  - Non-natural nucleotide substrates are widely used in the enzymatic synthesis of
      modified DNA. The terminal activity of polymerases in the presence of modified
      nucleotides is an important, but poorly characterized, aspect of enzymatic DNA
      synthesis. Here, we studied different types of polymerase activity at sequence
      ends using extendable and non-extendable synthetic models in the presence of the
      Cy5-dUTP analog Y. In primer extension reactions with selected exonuclease
      deficient polymerases, nucleotide Y appeared to be a preferential substrate for
      non-templated 3'-tailing, as determined by MALDI mass-spectrometry and gel
      electrophoresis. This result was further confirmed by the 3'-tailing of a non
      extendable hairpin oligonucleotide model. Additionally, DNA polymerases induce an
      exchange of the 3' terminal thymidine for a non-natural nucleotide via
      pyrophosphorolysis in the presence of inorganic pyrophosphate. In primer
      extension reactions, the proofreading polymerases Vent, Pfu, and Phusion did not
      support the synthesis of Y-modified primer strand. Nevertheless, Pfu and Phusion
      polymerases were shown to initiate terminal nucleotide exchange at the template.
      Unlike non-proofreading polymerases, these two enzymes recruit 3'-5' exonuclease
      functions to cleave the 3' terminal thymidine in the absence of pyrophosphate.

PMID- 28751642
TI  - Anti-obesity and anti-inflammatory effects of synthetic acetic acid vinegar and
      Nipa vinegar on high-fat-diet-induced obese mice.
AB  - Recently, food-based bioactive ingredients, such as vinegar, have been proposed
      as a potential solution to overcome the global obesity epidemic. Although acetic
      acid has been identified as the main component in vinegar that contributes to its
      anti-obesity effect, reports have shown that vinegar produced from different
      starting materials possess different degrees of bioactivity. This study was
      performed to compare the anti-obesity and anti-inflammatory effects of synthetic
      acetic acid vinegar and Nipa vinegar in mice fed a high-fat diet. In this work,
      mice were fed a high-fat diet for 33 weeks. At the start of week 24, obese mice
      were orally fed synthetic acetic acid vinegar or Nipa vinegar (0.08 and 2 ml/kg
      BW) until the end of week 33. Mice fed a standard pellet diet served as a
      control. Although both synthetic acetic acid vinegar and Nipa vinegar effectively
      reduced food intake and body weight, a high dose of Nipa vinegar more effectively
      reduced lipid deposition, improved the serum lipid profile, increased adipokine
      expression and suppressed inflammation in the obese mice. Thus, a high dose of
      Nipa vinegar may potentially alleviate obesity by altering the lipid metabolism,
      inflammation and gut microbe composition in high-fat-diet-induced obese mice.

PMID- 28751643
TI  - Fabrication of three-dimensional suspended, interlayered and hierarchical
      nanostructures by accuracy-improved electron beam lithography overlay.
AB  - Nanofabrication techniques are essential for exploring nanoscience and many
      closely related research fields such as materials, electronics, optics and
      photonics. Recently, three-dimensional (3D) nanofabrication techniques have been
      actively investigated through many different ways, however, it is still
      challenging to make elaborate and complex 3D nanostructures that many researchers
      want to realize for further interesting physics studies and device applications.
      Electron beam lithography, one of the two-dimensional (2D) nanofabrication
      techniques, is also feasible to realize elaborate 3D nanostructures by stacking
      each 2D nanostructures. However, alignment errors among the individual 2D
      nanostructures have been difficult to control due to some practical issues. In
      this work, we introduce a straightforward approach to drastically increase the
      overlay accuracy of sub-20 nm based on carefully designed alignmarks and
      calibrators. Three different types of 3D nanostructures whose designs are
      motivated from metamaterials and plasmonic structures have been demonstrated to
      verify the feasibility of the method, and the desired result has been achieved.
      We believe our work can provide a useful approach for building more advanced and
      complex 3D nanostructures.

PMID- 28751644
TI  - Minimal hepatic encephalopathy is associated with expansion and activation of
      CD4+CD28-, Th22 and Tfh and B lymphocytes.
AB  - Peripheral inflammation acts synergistically with hyperammonemia in inducing
      neurological alterations in cirrhotic patients with minimal hepatic
      encephalopathy (MHE). We hypothesized that appearance of MHE would be associated
      to some specific qualitative change in peripheral inflammation. The aim of this
      work was to characterize the changes in peripheral inflammation associated to
      appearance of MHE. We analyzed it by immunophenotyping and cytokine profile
      analysis, in cirrhotic patients without or with MHE and controls. The main
      alterations associated specifically with MHE are: 1) increased activation of all
      subtypes of CD4+ T-lymphocytes, with the increased expression of CD69; 2)
      increased amount of CD4+CD28- T lymphocytes, associated with increased levels of
      CX3CL1 and of IL-15; 3) increased differentiation of CD4+ T lymphocytes to Th
      follicular and Th22; 4) increased activation of B lymphocytes and serum IgG. This
      study has identified some specific alterations of the immune system associated
      with appearance of the neurological alterations in MHE patients.

PMID- 28751645
TI  - Visual adaptation alters the apparent speed of real-world actions.
AB  - The apparent physical speed of an object in the field of view remains constant
      despite variations in retinal velocity due to viewing conditions (velocity
      constancy). For example, people and cars appear to move across the field of view
      at the same objective speed regardless of distance. In this study a series of
      experiments investigated the visual processes underpinning judgements of
      objective speed using an adaptation paradigm and video recordings of natural
      human locomotion. Viewing a video played in slow-motion for 30 seconds caused
      participants to perceive subsequently viewed clips played at standard speed as
      too fast, so playback had to be slowed down in order for it to appear natural;
      conversely after viewing fast-forward videos for 30 seconds, playback had to be
      speeded up in order to appear natural. The perceived speed of locomotion shifted
      towards the speed depicted in the adapting video ('re-normalisation'). Results
      were qualitatively different from those obtained in previously reported studies
      of retinal velocity adaptation. Adapting videos that were scrambled to remove
      recognizable human figures or coherent motion caused significant, though smaller
      shifts in apparent locomotion speed, indicating that both low-level and high
      level visual properties of the adapting stimulus contributed to the changes in
      apparent speed.

PMID- 28751646
TI  - An Integrative Computational Approach to Evaluate Genetic Markers for Bipolar
      Disorder.
AB  - Studies to date have reported hundreds of genes connected to bipolar disorder
      (BP). However, many studies identifying candidate genes have lacked replication,
      and their results have, at times, been inconsistent with one another. This paper,
      therefore, offers a computational workflow that can curate and evaluate BP
      related genetic data. Our method integrated large-scale literature data and gene
      expression data that were acquired from both postmortem human brain regions (BP
      case/control: 45/50) and peripheral blood mononuclear cells (BP case/control:
      193/593). To assess the pathogenic profiles of candidate genes, we conducted
      Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analyses,
      with 4 metrics proposed and validated for each gene. Our approach developed a
      scalable BP genetic database (BP_GD), including BP related genes, drugs,
      pathways, diseases and supporting references. The 4 metrics successfully
      identified frequently-studied BP genes (e.g. GRIN2A, DRD1, DRD2, HTR2A, CACNA1C,
      TH, BDNF, SLC6A3, P2RX7, DRD3, and DRD4) and also highlighted several recently
      reported BP genes (e.g. GRIK5, GRM1 and CACNA1A). The computational biology
      approach and the BP database developed in this study could contribute to a better
      understanding of the current stage of BP genetic research and assist further
      studies in the field.

PMID- 28751647
TI  - Antiparallel RNA G-quadruplex Formed by Human Telomere RNA Containing 8
      Bromoguanosine.
AB  - In this study, by combining nuclear magnetic resonance (NMR), circular dichroism
      (CD), liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI
      MS), and gel electrophoresis, we report an unusual topological structure of the
      RNA G-quadruplex motif formed by human telomere RNA r(UAGGGU) containing 8
      bromoguanosine. Results showed that the RNA sequence formed an antiparallel
      tetramolecular G-quadruplex, in which each pair of diagonal strands run in
      opposite directions. Furthermore, guanosines were observed both in syn- and anti
      conformations. In addition, two of these G-quadruplex subunits were found to be
      stacking on top of each other, forming a dimeric RNA G-quadruplex. Our findings
      provide a new insight into the behavior of RNA G-quadruplex structures.

PMID- 28751648
TI  - Effects of ultrashort laser pulses on angular distributions of photoionization
      spectra.
AB  - We study the photoelectron spectra by intense laser pulses with arbitrary time
      dependence and phase within the Keldysh framework. An efficient semianalytical
      approach using analytical transition matrix elements for hydrogenic atoms in any
      initial state enables efficient and accurate computation of the photoionization
      probability at any observation point without saddle point approximation,
      providing comprehensive three dimensional photoelectron angular distribution for
      linear and elliptical polarizations, that reveal the intricate features and
      provide insights on the photoionization characteristics such as angular
      dispersions, shift and splitting of photoelectron peaks from the tunneling or
      above threshold ionization(ATI) regime to non-adiabatic(intermediate) and
      multiphoton ionization(MPI) regimes. This facilitates the study of the effects of
      various laser pulse parameters on the photoelectron spectra and their angular
      distributions. The photoelectron peaks occur at multiples of 2homega for linear
      polarization while  odd-ordered peaks are suppressed in the direction
      perpendicular to the electric field. Short pulses create splitting and angular
      dispersion where the peaks are strongly correlated to the angles. For MPI and
      elliptical polarization with shorter pulse s  the peaks split into doublets and
      the first peak vanishes. The carrier envelope phase(CEP) significantly affects
      the ATI spectra while the Stark effect shifts the spectra of intermediate regime
      to higher energies due to interference.

PMID- 28751649
TI  - Microsatellite markers for multiple Pocillopora genetic lineages offer new
      insights about coral populations.
AB  - Population genetics of the coral genus Pocillopora have been more intensively
      studied than those of any other reef-building taxon. However, recent
      investigations have revealed that the current morphological classification is
      inadequate to represent genetic lineages. In this study, we isolated and
      characterized novel microsatellite loci from morphological Pocillopora meandrina
      (Type 1) and Pocillopora acuta (Type 5). Furthermore, we characterized previously
      reported microsatellite loci. A total of 27 loci (13 novel loci) proved useful
      for population genetic analyses at two sites in the Ryukyu Archipelago, in the
      northwestern Pacific. Clonal diversity differed in each genetic lineage. Genetic
      structure suggested by microsatellites corresponded to clusters in a phylogenetic
      tree constructed from a mitochondrial open reading frame (mtORF). In addition, we
      found an unknown mitochondrial haplotype of this mtORF. These microsatellite loci
      will be useful for studies of connectivity and genetic diversity of Pocillopora
      populations, and will also support coral reef conservation.

PMID- 28751650
TI  - RhoA phosphorylation mediated by Rho/RhoA-associated kinase pathway improves the
      anti-freezing potentiality of murine hatched and diapaused blastocysts.
AB  - Embryonic cryopreservation has a relatively low survival rate because of
      cytoskeletal damage. However, molecular anti-freezing mechanisms have been
      largely unexplored. This study investigated the significance of RhoA, involved in
      embryonic development, and the Rho/RhoA-associated kinase (ROCK) signalling
      pathway in cryopreservation. The anti-freezing mechanism in murine dormant
      embryos, compared with normal blastocysts, was assessed by combining molecular,
      physiological and pharmacological approaches. Real-time PCR and western blotting
      experiments showed high RhoA expression in cryo-dormant and dormant embryos. RhoA
      GTPases were overexpressed on the surface of trophectoderm cells in dormant
      embryos. Treatment with Y-27632, a ROCK antagonist, decreased survival of both
      normal and dormant blastocysts, while recombinant RhoA protein remarkably
      increased survival, after freeze-thawing, of normal hatched blastocysts. Our
      findings elucidated the molecular mechanism of anti-freezing, involving RhoA
      phosphorylation, meditated by the Rho/ROCK signalling pathway, in hatched and
      diapaused murine blastocysts. In addition, evidence for a potentially protective
      additive suggests a new method for improving the anti-freezing potential of
      mammalian embryos, without protecting the zona pellucida.

PMID- 28751652
TI  - Fractal Electrodes as a Generic Interface for Stimulating Neurons.
AB  - The prospect of replacing damaged body parts with artificial implants is being
      transformed from science fiction to science fact through the increasing
      application of electronics to interface with human neurons in the limbs, the
      brain, and the retina. We propose bio-inspired electronics which adopt the
      fractal geometry of the neurons they interface with. Our focus is on retinal
      implants, although performance improvements will be generic to many neuronal
      types. The key component is a multifunctional electrode; light passes through
      this electrode into a photodiode which charges the electrode. Its electric field
      then stimulates the neurons. A fractal electrode might increase both light
      transmission and neuron proximity compared to conventional Euclidean electrodes.
      These advantages are negated if the fractal's field is less effective at
      stimulating neurons. We present simulations demonstrating how an interplay of
      fractal properties generates enhanced stimulation; the electrode voltage
      necessary to stimulate all neighboring neurons is over 50% less for fractal than
      Euclidean electrodes. This smaller voltage can be achieved by a single diode
      compared to three diodes required for the Euclidean electrode's higher voltage.
      This will allow patients, for the first time, to see with the visual acuity
      necessary for navigating rooms and streets.

PMID- 28751651
TI  - Targeting autophagy in cancer.
AB  - Autophagy is a mechanism by which cellular material is delivered to lysosomes for
      degradation, leading to the basal turnover of cell components and providing
      energy and macromolecular precursors. Autophagy has opposing, context-dependent
      roles in cancer, and interventions to both stimulate and inhibit autophagy have
      been proposed as cancer therapies. This has led to the therapeutic targeting of
      autophagy in cancer to be sometimes viewed as controversial. In this Review, we
      suggest a way forwards for the effective targeting of autophagy by understanding
      the context-dependent roles of autophagy and by capitalizing on modern approaches
      to clinical trial design.

PMID- 28751653
TI  - Biochemical profiling of diabetes disease progression by multivariate vibrational
      microspectroscopy of the pancreas.
AB  - Despite the dramatic increase in the prevalence of diabetes, techniques for in
      situ studies of the underlying pancreatic biochemistry are lacking. Such methods
      would facilitate obtaining mechanistic understanding of diabetes pathophysiology
      and aid in prognostic and/or diagnostic assessments. In this report we
      demonstrate how a multivariate imaging approach (orthogonal projections to latent
      structures - discriminant analysis) can be applied to generate full vibrational
      microspectroscopic profiles of pancreatic tissues. These profiles enable
      extraction of known and previously unrecorded biochemical alterations in models
      of diabetes, and allow for classification of the investigated tissue with regards
      to tissue type, strain and stage of disease progression. Most significantly, the
      approach provided evidence for dramatic alterations of the pancreatic
      biochemistry at the initial onset of immune-infiltration in the Non Obese
      Diabetic model for type 1 diabetes. Further, it enabled detection of a previously
      undocumented accumulation of collagen fibrils in the leptin deficient ob/ob mouse
      islets. By generating high quality spectral profiles through the tissue capsule
      of hydrated human pancreata and by in vivo Raman imaging of pancreatic islets
      transplanted to the anterior chamber of the eye, we provide critical feasibility
      studies for the translation of this technique to diagnostic assessments of
      pancreatic biochemistry in vivo.

PMID- 28751654
TI  - Pro-106-Ser mutation and EPSPS overexpression acting together simultaneously in
      glyphosate-resistant goosegrass (Eleusine indica).
AB  - Glyphosate has been used for more than 15 years for weed management in citrus
      groves in the Gulf of Mexico, at up to 3-4 applications per year. Goosegrass
      (Eleusine indica (L.) Gaertn.) control has sometimes failed. In this research,
      the mechanisms governing three goosegrass biotypes (Ein-Or from an orange grove,
      and Ein-Pl1 and Ein-Pl2 from Persian lime groves) with suspected resistance to
      glyphosate were characterized and compared to a susceptible biotype (Ein-S). Dose
      response and shikimate accumulation assays confirmed resistance of the resistant
      (R) biotypes. There were no differences in glyphosate absorption, but the R
      biotypes retained up to 62-78% of the herbicide in the treated leaf at 96 h after
      treatment (HAT), in comparison to the Ein-S biotype (36%). The 5
      enolpyruvylshikimate-3-phosphate synthase (EPSPS) activity in the Ein-Or and Ein
      S biotypes was over 100-fold lower than the Ein-Pl1 and Ein-Pl2 ones. The latter
      showed a high EPSPS-basal activity, a mutation at Pro-106-Ser position in the
      EPSPS gene, and EPSPS overexpression. The EPSPS basal and EPSPS overexpression
      were positively correlated. The R goosegrass biotypes displayed poor glyphosate
      translocation. Furthermore, this grassweed showed, for the first time, two
      mechanisms at the target-site level (Pro-106-Ser mutation + EPSPS overexpression)
      acting together simultaneously against glyphosate.

PMID- 28751655
TI  - Corrigendum: Nosocomial and Community-Acquired Spontaneous Bacterial Peritonitis
      in patients with liver cirrhosis in China: Comparative Microbiology and
      Therapeutic Implications.
AB  - This corrects the article DOI: 10.1038/srep46025.

PMID- 28751656
TI  - Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy.
AB  - Cones are responsible for daylight, central, high acuity and color vision. Three
      proteins found in human cones, i.e. long-wavelength (L)-, middle-wavelength (M)-,
      and short-wavelength sensitive (S)-opsins, are responsible for red, green and
      blue color recognition, respectively. Human blue cone monochromacy (BCM) is
      characterized by functional loss of both L- and M-cone opsins due to mutations in
      the OPN1LW/OPN1MW gene cluster on the X chromosome. BCM patients, who rely on
      their vision from only S-cones and rods, suffer severely reduced visual acuity
      and impaired color vision. Recent studies show that there is sufficient cone
      structure remaining in the central fovea of BCM patients to consider AAV-mediated
      gene augmentation therapy. In contrast, mouse retina has only two opsins, S-opsin
      and M-opsin, but no L-opsin. We generated an M-opsin knockout mouse (Opn1mw -/-)
      expressing only S-opsin as a model for human BCM. We show that recombinant M
      opsin delivered by AAV5 vectors rescues M-cone function in Opn1mw -/- mice. We
      also show that AAV delivered M-opsin localizes in the dorsal cone outer segments,
      and co-localizes with S-opsin in the ventral retina. Our study demonstrates that
      cones without M-opsin remain viable and respond to gene augmentation therapy,
      thereby providing proof-of-concept for cone function restoration in BCM patients.

PMID- 28751658
TI  - Unconscious perception and reverie: an intersubjective connection.
AB  - This paper discusses an intriguing topic for psychoanalysis: the concept of
      unconscious communication. Beginning with the concept of unconscious perception,
      it moves on to figurability and culminates with reverie. Auxiliary concepts, such
      as receptive unconscious, intersubjectivtiy, countertransferrence and empathy,
      are discussed in order to articulate the conceptual network on which theoretical
      arguments are based.

PMID- 28751659
TI  - Ferenczi's Revolutionary Therapeutic Approach.
AB  - Many of the revolutionary principles introduced by Ferenczi in his clinical
      practice have now been widely accepted especially in the field of trauma and
      trauma therapy. Examples of these innovative views include his emphasis on
      empathy as opposed to technical neutrality and his stress on the real conditions
      of child caring and family environmental deficits and on the consequences of
      interpersonal violence and abuse that lead to "identification with the aggressor"
      by the victim thereby resulting in the internalization of both aggressiveness and
      guilt (the split guilt of the abuser). The resulting "fragmentation" of the
      personality, which is now considered dissociation (instead of Freud's
      "repression"), is at the root of several severe disorders, characterized by
      distortion of reality, loss of touch with one's body and loss of trust in the
      other. Therefore "abreaction is not enough". A new, positive relational
      experience must be re-inscribed at the level of implicit memory.

PMID- 28751660
TI  - Something Was Lost in Freud's Beyond the Pleasure Principle: A Ferenczian
      Reading.
AB  - Freud's Beyond the Pleasure Principle (1920) brought a lot of new possibilities
      to psychoanalytic theory, but also a series of losses. While I recognize the
      importance of the death drive as a metapsychological construct, I argue that the
      first thing that went missing with the arrival of this groundbreaking Freudian
      text is the theorization of the ego instincts or the self-preservative drives.
      Freud never articulated some plausible inheritors of the ego instincts. I follow
      the Budapest School, and especially the voice of Sandor Ferenczi, for addressing
      this loss. The second thing that went missing after Beyond the Pleasure Principle
      is our openness in thinking through repetition. With the seductive formulation of
      the "daemonic" repetition in this 1920 text, our theoretical imagination around
      repetition seems to have been affected. I draw on the work of Sandor Ferenczi for
      exploring new forms of repetition. Finally, I offer a Ferenczian re-reading of
      the Freudian Nachtraglichkeit, which I see as crucial in the process of
      pluralizing our thinking on repetition.

PMID- 28751661
TI  - Imaging and mapping the impact of clouds on skyglow with all-sky photometry.
AB  - Artificial skyglow is constantly growing on a global scale, with potential
      ecological consequences ranging up to affecting biodiversity. To understand these
      consequences, worldwide mapping of skyglow for all weather conditions is urgently
      required. In particular, the amplification of skyglow by clouds needs to be
      studied, as clouds can extend the reach of skyglow into remote areas not affected
      by light pollution on clear nights. Here we use commercial digital single lens
      reflex cameras with fisheye lenses for all-sky photometry. We track the reach of
      skyglow from a peri-urban into a remote area on a clear and a partly cloudy night
      by performing transects from the Spanish town of Balaguer towards Montsec
      Astronomical Park. From one single all-sky image, we extract zenith luminance,
      horizontal and scalar illuminance. While zenith luminance reaches near-natural
      levels at 5 km distance from the town on the clear night, similar levels are only
      reached at 27 km on the partly cloudy night. Our results show the dramatic
      increase of the reach of skyglow even for moderate cloud coverage at this site.
      The powerful and easy-to-use method promises to be widely applicable for studies
      of ecological light pollution on a global scale also by non-specialists in
      photometry.

PMID- 28751662
TI  - L p -Adaptation: Simultaneous Design Centering and Robustness Estimation of
      Electronic and Biological Systems.
AB  - The design of systems or models that work robustly under uncertainty and
      environmental fluctuations is a key challenge in both engineering and science.
      This is formalized in the design-centering problem, which is defined as finding a
      design that fulfills given specifications and has a high probability of still
      doing so if the system parameters or the specifications fluctuate randomly.
      Design centering is often accompanied by the problem of quantifying the
      robustness of a system. Here we present a novel adaptive statistical method to
      simultaneously address both problems. Our method, L p -Adaptation, is inspired by
      the evolution of robustness in biological systems and by randomized schemes for
      convex volume computation. It is able to address both problems in the general,
      non-convex case and at low computational cost. We describe the concept and the
      algorithm, test it on known benchmarks, and demonstrate its real-world
      applicability in electronic and biological systems. In all cases, the present
      method outperforms the previous state of the art. This enables re-formulating
      optimization problems in engineering and biology as design centering problems,
      taking global system robustness into account.

PMID- 28751663
TI  - Caregiver burden in schizophrenia following paliperidone palmitate long acting
      injectables treatment: pooled analysis of two double-blind randomized phase three
      studies.
AB  - : The pooled analysis of two double-blind, randomized, multicenter, phase-3
      studies evaluated predictors of improvement or worsening of schizophrenia-related
      caregiver burden following paliperidone palmitate long-acting injectables (1
      monthly [PP1M] and 3-monthly [PP3M]) treatment. Caregivers were offered to
      complete the involvement evaluation questionnaire (involvement evaluation
      questionnaire; 31-item scale). Total, 1498 caregivers (intent-to-treat open-label
      analysis set, n = 1497; mean [SD] age: 51.5 [13.02] years, 27 countries) were
      included: 49% were parents and >50% caregivers spent >32 hours/week in
      caregiving. Majority of caregivers with considerable burden (n = 1405; mean [SD]
      baseline involvement evaluation questionnaire scores: 28.4 [15.07]) improved
      significantly from baseline to end-of-study (n = 756; mean [SD] change from open
      label baseline to double-blind endpoint in long-acting injectable scores:-8.9
      [14.73]); most improvements were seen in urging followed by worrying, tension,
      and supervision domains (mean [SD] change from open-label baseline to double
      blind endpoint in involvement evaluation questionnaire scores, urging: -3.7
      [6.45]; worrying:-2.6 [5.11]; tension:-2.3 [4.84]; supervision: -1.3 [3.69]).
      Improvements significantly correlated with relapse status, patient age, and age
      of diagnosis (p < 0.001) while long-acting injectable use at baseline, number,
      and duration of prior psychiatric hospitalizations (<24 months) had no
      significant correlation. Caregiver burden was significantly improved for patients
      on prior oral antipsychotics post-switching to long-acting injectable, with less
      impact on leisure days and hours spent in caregiving (p < 0.001). Family members
      of patients with schizophrenia experience considerable caregiver burden.
      Switching from oral antipsychotic to long-acting injectable can provide
      meaningful and significant improvement in caregiver burden. DRUG FORMULATION:
      EASING THE TOLL OF CAREGIVING: Switching from oral to long-acting injectable
      antipsychotic medication improves overall caregiver burden. The physical,
      emotional and financial toll of providing care for patients with schizophrenia is
      often underestimated. Poor adherence to conventional oral antipsychotics is a
      major cause of symptomatic relapse in patients and of stress for carers. Srihari
      Gopal and colleagues at Janssen Pharmaceuticals have pooled data from two large
      studies involving 1498 caregivers across 27 countries. They found that
      administration of either 1- or 3-monthly long-acting injectable antipsychotics
      not only eased the burden of daily dosing and patient compliance, but also had a
      positive impact on the stress conditions of caregivers. Using the Involvement
      Evaluation Questionnaire to measure caregiver burden, the authors showed that the
      switch in drug formulation decreased the need to urge patients to self-care and
      the hours spent caregiving.

PMID- 28751664
TI  - Afferent specific role of NMDA receptors for the circuit integration of
      hippocampal neurogliaform cells.
AB  - Appropriate integration of GABAergic interneurons into nascent cortical circuits
      is critical for ensuring normal information processing within the brain. Network
      and cognitive deficits associated with neurological disorders, such as
      schizophrenia, that result from NMDA receptor-hypofunction have been mainly
      attributed to dysfunction of parvalbumin-expressing interneurons that
      paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that
      throughout postnatal development, thalamic, and entorhinal cortical inputs onto
      hippocampal neurogliaform cells are characterized by a large NMDA receptor
      mediated component. This NMDA receptor-signaling is prerequisite for
      developmental programs ultimately responsible for the appropriate long-range
      AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated
      input at local Schaffer-collateral synapses on neurogliaform cells remains normal
      following NMDA receptor-ablation. These afferent specific deficits potentially
      impact neurogliaform cell mediated inhibition within the hippocampus and our
      findings reveal circuit loci implicating this relatively understudied interneuron
      subtype in the etiology of neurodevelopmental disorders characterized by NMDA
      receptor-hypofunction.Proper brain function depends on the correct assembly of
      excitatory and inhibitory neurons into neural circuits. Here the authors show
      that during early postnatal development in mice, NMDAR signaling via activity of
      long-range synaptic inputs onto neurogliaform cells is required for their
      appropriate integration into the hippocampal circuitry.

PMID- 28751665
TI  - Multidimensional integrative analysis uncovers driver candidates and biomarkers
      in penile carcinoma.
AB  - Molecular data generation and their combination in penile carcinomas (PeCa), a
      significant public health problem in poor and underdeveloped countries, remain
      virtually unexplored. An integrativemethodology combin ing genome-wide copy
      number alteration, DNA methylation, miRNA and mRNA expression analysis was
      performed in a set of 20 usual PeCa. The well-ranked 16 driver candidates
      harboring genomic alterations and regulated by a set of miRNAs, including hsa-miR
      31, hsa-miR-34a and hsa-miR-130b, were significantly associated with over
      represented pathways in cancer, such as immune-inflammatory system, apoptosis and
      cell cycle. Modules of co-expressed genes generated from expression matrix were
      associated with driver candidates and classified according to the over
      representation of passengers, thus suggesting an alteration of the pathway
      dynamics during the carcinogenesis. This association resulted in 10 top driver
      candidates (AR, BIRC5, DNMT3B, ERBB4, FGFR1, PML, PPARG, RB1, TNFSF10 and STAT1)
      selected and confirmed as altered in an independent set of 33 PeCa samples. In
      addition to the potential driver genes herein described, shorter overall survival
      was associated with BIRC5 and DNMT3B overexpression (log-rank test, P = 0.026 and
      P = 0.002, respectively) highlighting its potential as novel prognostic marker
      for penile cancer.

PMID- 28751666
TI  - CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal
      Epithelial Cells.
AB  - Mechanical stimulation of airway epithelial cells causes apical release of ATP,
      which increases ciliary beat frequency (CBF) and speeds up mucociliary clearance.
      The mechanisms responsible for this ATP release are poorly understood. CALHM1, a
      transmembrane protein with shared structural features to connexins and pannexins,
      has been implicated in ATP release from taste buds, but it has not been evaluated
      for a functional role in the airway. In the present study, Calhm1 knockout, Panx1
      knockout, and wild-type mouse nasal septal epithelial cells were grown at an air
      liquid interface (ALI) and subjected to light mechanical stimulation from an air
      puff. Apical ATP release was attenuated in Calhm1 knockout cultures following
      mechanical stimulation at a pressure of 55 mmHg for 50 milliseconds (p < 0.05).
      Addition of carbenoxolone, a PANX1 channel blocker, completely abolished ATP
      release in Calhm1 knockout cultures but not in wild type or Panx1 knockout
      cultures. An increase in CBF was observed in wild-type ALIs following mechanical
      stimulation, and this increase was significantly lower (p < 0.01) in Calhm1
      knockout cultures. These results demonstrate that CALHM1 plays a newly defined
      role, complementary to PANX1, in ATP release and downstream CBF modulation
      following a mechanical stimulus in airway epithelial cells.

PMID- 28751667
TI  - High diversity of the Ganzhou Oviraptorid Fauna increased by a new "cassowary
      like" crested species.
AB  - A new oviraptorid dinosaur from the Late Cretaceous of Ganzhou, bringing
      oviraptrotid diversity of this region to seven taxa, is described. It is
      characterized by a distinct cassowary-like crest on the skull, no pleurocoels on
      the centra from the second through fourth cervical vertebrae, a neck twice as
      long as the dorsal vertebral column and slightly longer than the forelimb
      (including the manus). Phylogenetic analysis recovers the new oviraptorid taxon,
      Corythoraptor jacobsi, as closely related to Huanansaurus from Ganzhou.
      Osteochronology suggests that the type specimen of Corythoraptor had not reached
      stationary growth stage but died while decreasing growth rates. The histology
      implies that it would correspond to an immature individual approximately eight
      years old. We hypothesize, based on the inner structure compared to that in
      modern cassowaries, that the prominent casque of Corythoraptor was a
      multifunction-structure utilized in display, communication and probably
      expression of the fitness during mating seasons.

PMID- 28751668
TI  - Signatures of a magnetic field-induced unconventional nematic liquid in the
      frustrated and anisotropic spin-chain cuprate LiCuSbO4.
AB  - Modern theories of quantum magnetism predict exotic multipolar states in weakly
      interacting strongly frustrated spin-1/2 Heisenberg chains with ferromagnetic
      nearest neighbor (NN) inchain exchange in high magnetic fields. Experimentally
      these states remained elusive so far. Here we report strong indications of a
      magnetic field-induced nematic liquid arising above a field of ~13 T in the edge
      sharing chain cuprate LiSbCuO4 = LiCuSbO4. This interpretation is based on the
      observation of a field induced spin-gap in the measurements of the 7Li NMR spin
      relaxation rate T 1-1 as well as a contrasting field-dependent power-law behavior
      of T 1-1 vs. T and is further supported by static magnetization and ESR data. An
      underlying theoretical microscopic approach favoring a nematic scenario is based
      essentially on the NN XYZ exchange anisotropy within a model for frustrated spin
      1/2 chains and is investigated by the DMRG technique. The employed exchange
      parameters are justified qualitatively by electronic structure calculations for
      LiCuSbO4.

PMID- 28751669
TI  - In-vivo loss of carbapenem resistance by extensively drug-resistant Klebsiella
      pneumoniae during treatment via porin expression modification.
AB  - Klebsiella pneumoniae, an Enterobacteriaceae that mostly causes hospital-acquired
      infections, belongs to the recently published WHO's list of antibiotic-resistant
      pathogens that pose the greatest threat to human health. Indeed, K. pneumoniae is
      the enterobacterial species most concerned by both resistance to extended
      spectrum cephalosporins, due to extended-spectrum beta-lactamase (ESBL)
      production, and resistance to carbapenems, i.e. the beta-lactams with the
      broadest activity. Carbapenem resistance is related not only to carbapenemase
      production, but also the production of ESBL or AmpC and the loss of general
      porins. Here, we characterized the mechanisms that deprived a urinary ESBL
      producing, porin-deficient K. pneumoniae isolate, isolated 13 days after the end
      of a 40-day course of imipenem treatment, of its carbapenem resistance. These
      mechanisms were observed in two in-vivo derivatives of this isolate and consisted
      of mutations in genes encoding molecules that participate in the downregulation
      of the synthesis of PhoE, a porin specialized in phosphate transport. We obtained
      three new derivatives from one of the two original derivatives, following in
      vitro antibiotic pressure, in which the carbapenem resistance was restored
      because of mutations in genes encoding molecules that participate in the
      upregulation of PhoE synthesis. Thus, we uncovered novel mechanisms of carbapenem
      resistance/susceptibility switching in K. pneumoniae.

PMID- 28751670
TI  - Inclusion of Population-specific Reference Panel from India to the 1000 Genomes
      Phase 3 Panel Improves Imputation Accuracy.
AB  - Imputation is a computational method based on the principle of haplotype sharing
      allowing enrichment of genome-wide association study datasets. It depends on the
      haplotype structure of the population and density of the genotype data. The 1000
      Genomes Project led to the generation of imputation reference panels which have
      been used globally. However, recent studies have shown that population-specific
      panels provide better enrichment of genome-wide variants. We compared the
      imputation accuracy using 1000 Genomes phase 3 reference panel and a panel
      generated from genome-wide data on 407 individuals from Western India (WIP). The
      concordance of imputed variants was cross-checked with next-generation re
      sequencing data on a subset of genomic regions. Further, using the genome-wide
      data from 1880 individuals, we demonstrate that WIP works better than the 1000
      Genomes phase 3 panel and when merged with it, significantly improves the
      imputation accuracy throughout the minor allele frequency range. We also show
      that imputation using only South Asian component of the 1000 Genomes phase 3
      panel works as good as the merged panel, making it computationally less intensive
      job. Thus, our study stresses that imputation accuracy using 1000 Genomes phase 3
      panel can be further improved by including population-specific reference panels
      from South Asia.

PMID- 28751671
TI  - Comparison of micro-CT imaging and histology for approximal caries detection.
AB  - Histological sectioning is a generally accepted in vitro validation method for
      caries detection techniques. However, it requires cumbersome sample preparation
      and induces irreversible sample destruction. Micro-Computer Tomography (micro-CT)
      allows non-destructive imaging of tooth structure. The aim of this study was to
      compare the performance of histological sectioning and micro-CT imaging in
      detecting approximal carious lesions. Unlike previous studies, evaluation is
      objectified by comparing visual appearance of exactly corresponding anatomical
      regions. Sixty extracted human teeth were scanned with a desktop micro CT system.
      Axial histological slices were prepared and photographed. Sample preparation,
      combined with dedicated image processing, ensured selection of identical
      anatomical regions on radiographic and histological images. Evaluation of the
      presence and extent of carious lesions was performed by four dentists using
      custom-designed software. Each section was scored independently (histo or micro
      CT). Scores of approximal surfaces were retained for further analysis. Spearman's
      correlation coefficients (0.738 to 0.829, p < 0.0001) showed a good agreement
      between signs of carious lesions in the identical region obtained with both
      methods. Bland-Altman plots showed that 90.76% of the data points were within the
      limits of agreement. Micro-CT imaging was shown to provide an interesting
      alternative to histological sectioning as detection method for carious lesions.

PMID- 28751672
TI  - The LncRNA Connectivity Map: Using LncRNA Signatures to Connect Small Molecules,
      LncRNAs, and Diseases.
AB  - Well characterized the connections among diseases, long non-coding RNAs (lncRNAs)
      and drugs are important for elucidating the key roles of lncRNAs in biological
      mechanisms in various biological states. In this study, we constructed a database
      called LNCmap (LncRNA Connectivity Map), available at http://www.bio
      bigdata.com/LNCmap/ , to establish the correlations among diseases, physiological
      processes, and the action of small molecule therapeutics by attempting to
      describe all biological states in terms of lncRNA signatures. By reannotating the
      microarray data from the Connectivity Map database, the LNCmap obtained 237
      lncRNA signatures of 5916 instances corresponding to 1262 small molecular drugs.
      We provided a user-friendly interface for the convenient browsing, retrieval and
      download of the database, including detailed information and the associations of
      drugs and corresponding affected lncRNAs. Additionally, we developed two
      enrichment analysis methods for users to identify candidate drugs for a
      particular disease by inputting the corresponding lncRNA expression profiles or
      an associated lncRNA list and then comparing them to the lncRNA signatures in our
      database. Overall, LNCmap could significantly improve our understanding of the
      biological roles of lncRNAs and provide a unique resource to reveal the
      connections among drugs, lncRNAs and diseases.

PMID- 28751673
TI  - III-Nitride Digital Alloy: Electronics and Optoelectronics Properties of the
      InN/GaN Ultra-Short Period Superlattice Nanostructures.
AB  - The III-Nitride digital alloy (DA) is comprehensively studied as a short-period
      superlattice nanostructure consisting of ultra-thin III-Nitride epitaxial layers.
      By stacking the ultra-thin III-Nitride epitaxial layers periodically, these
      nanostructures are expected to have comparable optoelectronic properties as the
      conventional III-Nitride alloys. Here we carried out numerical studies on the
      InGaN DA showing the tunable optoelectronic properties of the III-Nitride DA. Our
      study shows that the energy gap of the InGaN DA can be tuned from ~0.63 eV up to
      ~2.4 eV, where the thicknesses and the thickness ratio of each GaN and InN ultra
      thin binary layers within the DA structure are the key factors for tuning
      bandgap. Correspondingly, the absorption spectra of the InGaN DA yield broad
      wavelength tunability which is comparable to that of bulk InGaN ternary alloy. In
      addition, our investigation also reveals that the electron-hole wavefunction
      overlaps are remarkably large in the InGaN DA structure despite the existence of
      strain effect and build-in polarization field. Our findings point out the
      potential of III-Nitride DA as an artificially engineered nanostructure for
      optoelectronic device applications.

PMID- 28751674
TI  - Honokiol suppresses formyl peptide-induced human neutrophil activation by
      blocking formyl peptide receptor 1.
AB  - Formyl peptide receptor 1 (FPR1) mediates bacterial and mitochondrial N-formyl
      peptides-induced neutrophil activation. Therefore, FPR1 is an important
      therapeutic target for drugs to treat septic or sterile inflammatory diseases.
      Honokiol, a major bioactive compound of Magnoliaceae plants, possesses several
      anti-inflammatory activities. Here, we show that honokiol exhibits an inhibitory
      effect on FPR1 binding in human neutrophils. Honokiol inhibited superoxide anion
      generation, reactive oxygen species formation, and elastase release in bacterial
      or mitochondrial N-formyl peptides (FPR1 agonists)-activated human neutrophils.
      Adhesion of FPR1-induced human neutrophils to cerebral endothelial cells was also
      reduced by honokiol. The receptor-binding results revealed that honokiol
      repressed FPR1-specific ligand N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein
      binding to FPR1 in human neutrophils, neutrophil-like THP-1 cells, and hFPR1
      transfected HEK293 cells. However, honokiol did not inhibit FPR2-specific ligand
      binding to FPR2 in human neutrophils. Furthermore, honokiol inhibited FPR1
      agonist-induced calcium mobilization as well as phosphorylation of p38 MAPK, ERK,
      and JNK in human neutrophils. In conclusion, our data demonstrate that honokiol
      may have therapeutic potential for treating FPR1-mediated inflammatory diseases.

PMID- 28751675
TI  - Cell-cycle arrest in mature adipocytes impairs BAT development but not WAT
      browning, and reduces adaptive thermogenesis in mice.
AB  - We previously reported brown adipocytes can proliferate even after
      differentiation. To test the involvement of mature adipocyte proliferation in
      cell number control in fat tissue, we generated transgenic (Tg) mice over
      expressing cell-cycle inhibitory protein p27 specifically in adipocytes, using
      the aP2 promoter. While there was no apparent difference in white adipose tissue
      (WAT) between wild-type (WT) and Tg mice, the amount of brown adipose tissue
      (BAT) was much smaller in Tg mice. Although BAT showed a normal cellular
      morphology, Tg mice had lower content of uncoupling protein 1 (UCP1) as a whole,
      and attenuated cold exposure- or beta3-adrenergic receptor (AR) agonist-induced
      thermogenesis, with a decrease in the number of mature brown adipocytes
      expressing proliferation markers. An agonist for the beta3-AR failed to increase
      the number of proliferating brown adipocytes, UCP1 content in BAT, and oxygen
      consumption in Tg mice, although the induction and the function of beige
      adipocytes in inguinal WAT from Tg mice were similar to WT mice. These results
      show that brown adipocyte proliferation significantly contributes to BAT
      development and adaptive thermogenesis in mice, but not to induction of beige
      adipocytes.

PMID- 28751676
TI  - Security enhanced memory for quantum state.
AB  - Security enhancement is important in terms of both classical and quantum
      information. The recent development of a quantum storage device is noteworthy,
      and a coherence time of one second or longer has been demonstrated. On the other
      hand, although the encryption of a quantum bit or quantum memory has been
      proposed theoretically, no experiment has yet been carried out. Here we report
      the demonstration of a quantum memory with an encryption function that is
      realized by scrambling and retrieving the recorded quantum phase. We developed
      two independent Ramsey interferometers on an atomic ensemble trapped below a
      persistent supercurrent atom chip. By operating the two interferometers with
      random phases, the quantum phase recorded by a pulse of the first interferometer
      was modulated by the second interferometer pulse. The scrambled quantum phase was
      restored by employing another pulse of the second interferometer with a specific
      time delay. This technique paves way for improving the security of quantum
      information technology.

PMID- 28751677
TI  - Nontuberculous mycobacteria in Denmark, incidence and clinical importance during
      the last quarter-century.
AB  - Disease caused by nontuberculous mycobacteria (NTM) is reported to increase due
      to an ageing population and a rise in the proportion of immunosuppressed
      patients. We did a retrospective cohort study of NTM-disease in the Danish
      population through a quarter-century to determine the disease burden and trends
      in annual incidence rates. 524,119 clinical specimens were cultured for
      mycobacteria from 1991 through 2015 at the International Reference Laboratory of
      Mycobacteriology in Denmark. Among these, 8,227 NTM strains were identified from
      3,462 patients and distributed according to microbiological disease criteria. We
      observed no increase in NTM disease incidence or proportion of patients with
      positive NTM cultures during the study period (Quasi-Poisson regression, p =
      0.275 and 0.352 respectively). Annual incidence rates were 1.20/105 for definite
      NTM disease, 0.49/105 for possible NTM disease and 0.88/105 for NTM colonization.
      The incidence rate of NTM disease was highest in children aged 0-4 years
      (5.36/105/year), predominantly with cervical Mycobacterium avium complex (MAC)
      adenitis. Surprisingly, based on more than half a million clinical specimens
      cultured for mycobacteria in Denmark through 25 years, the NTM disease burden and
      trend in incidence in the Danish population has not increased opposed to numerous
      internationals reports.

PMID- 28751678
TI  - Morpho-functional characterization of the systemic venous pole of the reptile
      heart.
AB  - Mammals evolved from reptile-like ancestors, and while the mammalian heart is
      driven by a distinct sinus node, a sinus node is not apparent in reptiles. We
      characterized the myocardial systemic venous pole, the sinus venosus, in reptiles
      to identify the dominant pacemaker and to assess whether the sinus venosus
      remodels and adopts an atrium-like phenotype as observed in mammals. Anolis
      lizards had an extensive sinus venosus of myocardium expressing Tbx18. A small
      sub-population of cells encircling the sinuatrial junction expressed Isl1, Bmp2,
      Tbx3, and Hcn4, homologues of genes marking the mammalian sinus node. Electrical
      mapping showed that hearts of Anolis lizards and Python snakes were driven from
      the sinuatrial junction. The electrical impulse was delayed between the sinus
      venosus and the right atrium, allowing the sinus venosus to contract and aid
      right atrial filling. In proximity of the systemic veins, the Anolis sinus
      venosus expressed markers of the atrial phenotype Nkx2-5 and Gja5. In conclusion,
      the reptile heart is driven by a pacemaker region with an expression signature
      similar to that of the immature sinus node of mammals. Unlike mammals, reptiles
      maintain a sinuatrial delay of the impulse, allowing the partly atrialized sinus
      venosus to function as a chamber.

PMID- 28751679
TI  - Conjugated Linoleic Acid Supplementation Improves Maternal High Fat Diet-Induced
      Programming of Metabolic Dysfunction in Adult Male Rat Offspring.
AB  - The developmental origins of health and disease hypothesis proposes that an
      adverse early life environment, including in utero exposure to a maternal
      obesogenic environment, can lead to an increased long-term risk of obesity and
      related metabolic complications in offspring. We assessed whether maternal
      supplementation with conjugated linoleic acid (CLA) could prevent some of these
      adverse effects in offspring exposed to a maternal high fat diet. Sprague-Dawley
      dams consumed either a: control (CD), control with CLA (CLA), high fat (HF) or
      high fat with CLA (HFCLA) diet 10 days prior to mating and throughout
      pregnancy/lactation. Male offspring were weaned onto a standard chow diet. Body
      composition was quantified by DXA and oral glucose tolerance tests conducted on
      adult offspring. Gene/protein expression and histological analysis were conducted
      in adipose tissue. Offspring from HF dams had increased body weight, body fat
      deposition, impaired insulin sensitivity and adipocyte hypertrophy; all of which
      were rescued in HFCLA offspring. Molecular and histological analyses of the
      adipose tissue suggest that disturbances in adipogenesis may mediate the
      metabolic dysfunction observed in HF offspring. Therefore, CLA supplementation to
      a maternal obesogenic diet may be a promising strategy to prevent adverse
      programming outcomes.

PMID- 28751680
TI  - Limits of Risk Predictability in a Cascading Alternating Renewal Process Model.
AB  - Most risk analysis models systematically underestimate the probability and impact
      of catastrophic events (e.g., economic crises, natural disasters, and terrorism)
      by not taking into account interconnectivity and interdependence of risks. To
      address this weakness, we propose the Cascading Alternating Renewal Process
      (CARP) to forecast interconnected global risks. However, assessments of the
      model's prediction precision are limited by lack of sufficient ground truth data.
      Here, we establish prediction precision as a function of input data size by using
      alternative long ground truth data generated by simulations of the CARP model
      with known parameters. We illustrate the approach on a model of fires in
      artificial cities assembled from basic city blocks with diverse housing. The
      results confirm that parameter recovery variance exhibits power law decay as a
      function of the length of available ground truth data. Using CARP, we also
      demonstrate estimation using a disparate dataset that also has dependencies: real
      world prediction precision for the global risk model based on the World Economic
      Forum Global Risk Report. We conclude that the CARP model is an efficient method
      for predicting catastrophic cascading events with potential applications to
      emerging local and global interconnected risks.

PMID- 28751681
TI  - Si Wire Supported MnO2/Al/Fluorocarbon 3D Core/Shell Nanoenergetic Arrays with
      Long-Term Storage Stability.
AB  - Three-dimensional MnO2/Al/fluorocarbon core/shell nanoenergetic arrays are
      prepared on silicon substrate that is with silicon wires on top. Silicon wires
      are first prepared as the scaffolds by maskless deep reactive ion etching of
      silicon wafer, which is followed by the hydrothermal growth of MnO2. Al and
      fluorocarbon are then deposited sequentially around the silicon wire (Si-W)
      supported MnO2 arrays by magnetron sputtering to realize the core/shell
      nanoenergetic composite. Several characterization techniques are used to
      investigate the prepared Si-W/MnO2/Al/fluorocarbon arrays, including the scanning
      electron microscopy, transmission electron microscopy, energy dispersive
      spectroscopy, X-ray photoelectron spectroscopy, and thermal analysis. 3D upright
      aligned core/shell structure with an intimate contact between MnO2 and Al is
      confirmed from the morphological characterization. Superhydrophobicity is
      achieved after the fluorocarbon coating. Most importantly, the Si
      W/MnO2/Al/fluorocarbon nanoenergetic arrays show no decay of energy density after
      9 months of storage, indicating potential applications in nanoenergetics-on-a
      chip when long-term storage is needed.

PMID- 28751682
TI  - Evolution, expression and association of the chemosensory protein genes with the
      outbreak phase of the two main pest locusts.
AB  - We analyze the evolutionary relationships and expression patterns of the large
      set of genes for chemosensory proteins (CSPs) in the two main pest locusts. We
      used the available transcriptome and genome data to infer the number of genes
      using BLAST searches and sequence similarity matrices. Maximum likelihood
      phylogenies revealed the relationships between these CSPs and CSPs from several
      arthropods. RNAseq and qPCR allowed associating CSPs to locust phases. Crossing
      the phylogenetic and expression data allowed us to deduce homologies and
      conservation of the involvement in the phase change. We confirm that Locusta
      migratoria has at least 58 CSP gene copies, only five of which lack evidence of
      expression, and we reveal that Schistocerca gregaria has at least 42 expressed
      CSP genes. Both species share 21 orthologs, whereas 33 L. migratoria and 15 S.
      gregaria CSPs seem species-specific. Additional six S. gregaria and four L.
      migratoria CSPs seem duplications. Although the expression profiles are not
      especially conserved, seven orthologous CSP pairs share a gregarious over
      expression pattern in adult locusts. We thus confirm that the number of locusts'
      CSPs is large, due to gene duplications during the evolution of Orthoptera, we
      establish sequence and potential functional homologies, and we highlight specific
      CSPs that appear to be involved in locust gregariousness either in general or in
      a species-specific manner.

PMID- 28751683
TI  - Corrigendum: A multiply-add engine with monolithically integrated 3D memristor
      crossbar/CMOS hybrid circuit.
AB  - This corrects the article DOI: 10.1038/srep42429.

PMID- 28751684
TI  - Lower Cretaceous fossils from China shed light on the ancestral body plan of
      crown softshell turtles (Trionychidae, Cryptodira).
AB  - Pan-trionychids or softshell turtles are a highly specialized and widespread
      extant group of aquatic taxa with an evolutionary history that goes back to the
      Early Cretaceous. The earliest pan-trionychids had already fully developed the
      "classic" softshell turtle morphology and it has been impossible to resolve
      whether they are stem members of the family or are within the crown. This has
      hindered our understanding of the evolution of the two basic body plans of crown
      trionychids. Thus it remains unclear whether the more heavily ossified shell of
      the cyclanorbines or the highly reduced trionychine morphotype is the ancestral
      condition for softshell turtles. A new pan-trionychid from the Early Cretaceous
      of Zhejiang, China, Perochelys hengshanensis sp. nov., allows a revision of
      softshell-turtle phylogeny. Equal character weighting resulted in a topology that
      is fundamentally inconsistent with molecular divergence date estimates of deeply
      nested extant species. In contrast, implied weighting retrieved Lower Cretaceous
      Perochelys spp. and Petrochelys kyrgyzensis as stem trionychids, which is fully
      consistent with their basal stratigraphic occurrence and an Aptian-Santonian
      molecular age estimate for crown-trionychids. These results indicate that the
      primitive morphology for soft-shell turtles is a poorly ossified shell like that
      of crown-trionychines and that shell re-ossification in cyclanorbines (including
      re-acquisition of peripheral elements) is secondary.

PMID- 28751685
TI  - Comparison of commercial ELISA assays for quantification of corticosterone in
      serum.
AB  - Enzyme-linked immunosorbent assay (ELISA) kits are widely used to quantify
      corticosterone levels for the assessment of stress in laboratory animals. The aim
      of this experiment was simply to evaluate if four different and widely used
      commercial ELISA assays would yield the same or similar values of corticosterone
      in serum samples taken from laboratory rats after the mild stress of being held
      for sampling blood from the saphenous vein. Trunk blood was sampled from 32 male
      Wistar rats 30 minutes after this mild stress exposure and analysed with each of
      four commercial ELISA kits. Both the Arbor Assays and the DRG-4164 kits were
      significantly higher than the DRG-5186 and the Enzo kits. There were no
      significant differences between the DRG-5186 and Enzo kits. Overall the
      correlations between kits were high. In conclusion, the commercial ELISA kits
      tested in the present experiment yielded different values of total corticosterone
      in the same serum samples. The precision in determining true values of the
      corticosterone level is low for these commercial ELISA kits, although they may be
      used to determine relative differences within studies.

PMID- 28751686
TI  - Carbon stocks and changes of dead organic matter in China's forests.
AB  - Forests play an important role in global carbon cycles. However, the lack of
      available information on carbon stocks in dead organic matter, including woody
      debris and litter, reduces the reliability of assessing the carbon cycles in
      entire forest ecosystems. Here we estimate that the national DOM carbon stock in
      the period of 2004-2008 is 925 +/- 54 Tg, with an average density of 5.95 +/-
      0.35 Mg C ha-1. Over the past two decades from periods of 1984-1988 to 2004-2008,
      the national dead organic matter carbon stock has increased by 6.7 +/- 2.2 Tg
      carbon per year, primarily due to increasing forest area. Temperature and
      precipitation increase the carbon density of woody debris, but decrease that of
      litter. Additionally, the woody debris increases significantly with above ground
      biomass and forest age. Our results can improve estimates of the carbon budget in
      China's forests and for better understanding of effects of climate and stand
      characteristics on dead organic matter distribution.Reliable estimates of the
      total forest carbon (C) pool are lacking due to insufficient information on dead
      organic matter (DOM). Here, the authors estimate that the current DOM C stock in
      China is 925 +/- 54 Tg and that it grew by 6.7 +/- 2.2 Tg C/yr over the past two
      decades primarily due to increasing forest area.

PMID- 28751687
TI  - Characterization and expression analysis of the WRKY gene family in moso bamboo.
AB  - The WRKY family of transcription factors (TFs) is one of the ten largest families
      of TFs in higher plants and has been implicated in multiple biological processes.
      Here, we identified 121 WRKY TFs in moso bamboo, including five novel members
      that were not annotated in the Phyllostachys edulis genomic database. Estimation
      of the divergence time of paralogous gene pairs revealed an important role of the
      recent whole-genome duplication in the expansion of the WRKY family. Expression
      analysis based on quantitative reverse-transcription polymerase chain reaction
      (qRT-PCR) data revealed that a large number of PheWRKY genes varied significantly
      under cold or drought stress treatments, which could be defined as abiotic stress
      responsive genes. The overexpression of PheWRKY72-2 in Arabidopsis resulted in a
      decreased sensitivity to drought stress during early seedling growth. PheWRKY72-2
      may enhance plant tolerance to stress by functioning as a positive regulator of
      stoma closure. Our study provides a theoretical foundation and some experimental
      evidence for further functional verification of the PheWRKY family of TFs.

PMID- 28751688
TI  - Enhanced efficiency of cell death by lysosome-specific photodamage.
AB  - Mobilization of specific mechanisms of regulated cell death is a promising
      alternative to treat challenging illness such as neurodegenerative disease and
      cancer. The use of light to activate these mechanisms may provide a route for
      target-specific therapies. Two asymmetric porphyrins with opposite charges, the
      negatively charged TPPS2a and the positively charged CisDiMPyP were compared in
      terms of their properties in membrane mimics and in cells. CisDiMPyP interacts to
      a larger extent with model membranes and with cells than TPPS2a, due to a
      favorable electrostatic interaction. CisDiMPyP is also more effective than TPPS2a
      in damaging membranes. Surprisingly, TPPS2a is more efficient in causing
      photoinduced cell death. The lethal concentration on cell viability of 50% (LC50)
      found for TPPS2a was ~3.5 (raw data) and ~5 (considering photosensitizer
      incorporation) times smaller than for CisDiMPyP. CisDiMPyP damaged mainly
      mitochondria and triggered short-term phototoxicity by necro-apoptotic cell
      death. Photoexcitation of TPPS2a promotes mainly lysosomal damage leading to
      autophagy-associated cell death. Our data shows that an exact damage in lysosome
      is more effective to diminish proliferation of HeLa cells than a similar damage
      in mitochondria. Precisely targeting organelles and specifically triggering
      regulated cell death mechanisms shall help in the development of new organelle
      target therapies.

PMID- 28751689
TI  - In silico, in vitro, X-ray crystallography, and integrated strategies for
      discovering spermidine synthase inhibitors for Chagas disease.
AB  - Chagas disease results from infection by Trypanosoma cruzi and is a neglected
      tropical disease (NTD). Although some treatment drugs are available, their use is
      associated with severe problems, including adverse effects and limited
      effectiveness during the chronic disease phase. To develop a novel anti-Chagas
      drug, we virtually screened 4.8 million small molecules against spermidine
      synthase (SpdSyn) as the target protein using our super computer "TSUBAME2.5" and
      conducted in vitro enzyme assays to determine the half-maximal inhibitory
      concentration values. We identified four hit compounds that inhibit T. cruzi
      SpdSyn (TcSpdSyn) by in silico and in vitro screening. We also determined the
      TcSpdSyn-hit compound complex structure using X-ray crystallography, which shows
      that the hit compound binds to the putrescine-binding site and interacts with
      Asp171 through a salt bridge.

PMID- 28751690
TI  - microRNA-352 regulates collateral vessel growth induced by elevated fluid shear
      stress in the rat hind limb.
AB  - Although collateral vessel growth is distinctly enhanced by elevated fluid shear
      stress (FSS), the underlying regulatory mechanism of this process remains
      incompletely understood. Recent studies have shown that microRNAs (miRNAs) play a
      pivotal role in vascular development, homeostasis and a variety of diseases.
      Therefore, this study was designed to identify miRNAs involved in elevated FSS
      induced collateral vessel growth in rat hind limbs. A side-to-side arteriovenous
      (AV) shunt was created between the distal stump of one of the bilaterally
      occluded femoral arteries and the accompanying vein. The miRNA array profile
      showed 94 differentially expressed miRNAs in FSS-stressed collaterals including
      miRNA-352 which was down-regulated. Infusion of antagomir-352 increased the
      number and proliferation of collateral vessels and promoted collateral flow
      restoration in a model of rat hind limb ligation. In cell culture studies, the
      miR-352 inhibitor increased endothelial proliferation, migration and tube
      formation. In addition, antagomir-352 up-regulated the expression of insulin-like
      growth factor II receptor (IGF2R), which may play a part in the complex pathway
      leading to arterial growth. We conclude that enhanced collateral vessel growth is
      controlled by miRNAs, among which miR-352 is a novel candidate that negatively
      regulates arteriogenesis, meriting additional studies to unravel the pathways
      leading to improved collateral circulation.

PMID- 28751691
TI  - A deletion affecting an LRR-RLK gene co-segregates with the fruit flat shape
      trait in peach.
AB  - In peach, the flat phenotype is caused by a partially dominant allele in
      heterozygosis (Ss), fruits from homozygous trees (SS) abort a few weeks after
      fruit setting. Previous research has identified a SSR marker (UDP98-412) highly
      associated with the trait, found suitable for marker assisted selection (MAS).
      Here we report a ~10 Kb deletion affecting the gene PRUPE.6G281100, 400 Kb
      upstream of UDP98-412, co-segregating with the trait. This gene is a leucine-rich
      repeat receptor-like kinase (LRR-RLK) orthologous to the Brassinosteroid
      insensitive 1-associated receptor kinase 1 (BAK1) group. PCR markers suitable for
      MAS confirmed its strong association with the trait in a collection of 246
      cultivars. They were used to evaluate the DNA from a round fruit derived from a
      somatic mutation of the flat variety 'UFO-4', revealing that the mutation
      affected the flat associated allele (S). Protein BLAST alignment identified
      significant hits with genes involved in different biological processes. Best
      protein hit occurred with AtRLP12, which may functionally complement CLAVATA2, a
      key regulator that controls the stem cell population size. RT-PCR analysis
      revealed the absence of transcription of the partially deleted allele. The data
      support PRUPE.6G281100 as a candidate gene for flat shape in peach.

PMID- 28751693
TI  - Physicians - Oral Sessions.

PMID- 28751692
TI  - CT-perfusion stroke imaging: a threshold free probabilistic approach to predict
      infarct volume compared to traditional ischemic thresholds.
AB  - The aim was to evaluate a novel method of threshold-free prediction of brain
      infarct from computed tomography perfusion (CTP) imaging in comparison to
      conventional ischemic thresholds. In a multicenter cohort of 161 patients with
      acute large vessel occlusion who received endovascular therapy, brain infarction
      was predicted by CTP using (1) optimized parameter cut-off values determined by
      ROC curve analysis and (2) probabilistic logistic regression threshold-free
      analysis. Predicted infarct volumes and prediction errors based on four perfusion
      parameter maps were compared against observed infarcts. In 93 patients with
      successful recanalization, the mean observed infarct volume was 35.7 +/- 61.9 ml
      (the reference for core infarct not savable by reperfusion). Optimal parameter
      thresholds predicted mean infarct volumes between 53.2 +/- 44.4 and 125.0 +/-
      95.4 ml whereas threshold-free analysis predicted mean volumes between 35.9 +/-
      28.5 and 36.1 +/- 29.0 ml. In 68 patients with persistent occlusion, the mean
      observed infarct volume was 113.4 +/- 138.3 ml (the reference to define penumbral
      infarct savable by reperfusion). Predicted mean infarct volumes by parameter
      thresholds ranged from 91.4 +/- 81.5 to 163.8 +/- 135.7 ml, by threshold-free
      analysis from 113.2 +/- 89.9 to 113.5 +/- 89.0 ml. Threshold-free prediction of
      infarct volumes had a higher precision and lower patient-specific prediction
      error than conventional thresholding. Penumbra to core lesion mismatch estimate
      may therefore benefit from threshold-free CTP analysis.

PMID- 28751695
TI  - Quality Management Group - Poster Session.

PMID- 28751694
TI  - Organising Committee.

PMID- 28751696
TI  - Welcome Address.

PMID- 28751697
TI  - EBMT Data Management Group - Poster Session.

PMID- 28751698
TI  - Van Bekkum Awards 1998-2017.

PMID- 28751699
TI  - Working Parties.

PMID- 28751700
TI  - EBMT Nurses Group - Oral Sessions.

PMID- 28751701
TI  - Physicians - Poster Session.

PMID- 28751702
TI  - EBMT Lectures 1998-2017.

PMID- 28751703
TI  - EBMT Nurses Group - Poster Session.

PMID- 28751705
TI  - Statistical Symposium - Oral Session.

PMID- 28751704
TI  - Physicians Abstracts.

PMID- 28751707
TI  - Quality Management Group - Oral Session.

PMID- 28751708
TI  - Using persistent photoconductivity to write a low-resistance path in SrTiO3.
AB  - Materials with persistent photoconductivity (PPC) experience an increase in
      conductivity upon exposure to light that persists after the light is turned off.
      Although researchers have shown that this phenomenon could be exploited for novel
      memory storage devices, low temperatures (below 180 K) were required. In the
      present work, two-point resistance measurements were performed on annealed
      strontium titanate (SrTiO3, or STO) single crystals at room temperature. After
      illumination with sub-gap light, the resistance decreased by three orders of
      magnitude. This markedly enhanced conductivity persisted for several days in the
      dark. Results from IR spectroscopy, electrical measurements, and exposure to a
      405 nm laser suggest that contact resistance plays an important role. The laser
      was then used as an "optical pen" to write a low-resistance path between two
      contacts, demonstrating the feasibility of optically defined, transparent
      electronics.

PMID- 28751709
TI  - Lymph node ratio is associated with adverse clinicopathological features and is a
      crucial nodal parameter for oral and oropharyngeal cancer.
AB  - The lymph node ratio(LNR) has been described as a novel predictor of the survival
      of patients with oral and oropharyngeal squamous cell carcinoma(O/OPSCC). The
      purpose of this study was to evaluate whether LNR is better at predicting
      survival and the need for adjuvant treatment than traditional tumour-nodal
      metastasis(TNM) staging. Eight hundred nine patients with O/OPSCC and positive
      lymph node disease were retrospectively enrolled in this study. LNR equal to
      0.075 is the best cut-off value for stratifying 5-year disease-free
      survival(DFS). High LNR is closely associated with more advanced T stage, higher
      N stage, more severe pathological grade, the presence of diffuse infiltration and
      extracapsular spread(ECS). LNR is better for evaluating prognosis than the
      pathological N stage. Patients with high LNR coupled with high number of positive
      lymph nodes who received adjuvant concurrent chemo-radiotherapy(CCRT) had a
      better 5-year DFS than patients who received surgery alone. Multivariate analyses
      revealed that T stage, ECS and LNR are independent prognostic factors of 5-year
      DFS and disease-specific survival(DSS). Therefore, high LNR is closely correlated
      with adverse parameters that markedly hinder prognosis. LNR is superior to
      traditional TNM staging for the evaluation of prognosis,and the combination of
      the LNR with the number of positive lymph nodes can predict the benefits of
      adjuvant CCRT.

PMID- 28751710
TI  - Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore
      microtubule attachments in human cells.
AB  - Human chromosomes are captured along microtubule walls (lateral attachment) and
      then tethered to microtubule-ends (end-on attachment) through a multi-step end-on
      conversion process. Upstream regulators that orchestrate this remarkable change
      in the plane of kinetochore-microtubule attachment in human cells are not known.
      By tracking kinetochore movements and using kinetochore markers specific to
      attachment status, we reveal a spatially defined role for Aurora-B kinase in
      retarding the end-on conversion process. To understand how Aurora-B activity is
      counteracted, we compare the roles of two outer-kinetochore bound phosphatases
      and find that BubR1-associated PP2A, unlike KNL1-associated PP1, plays a
      significant role in end-on conversion. Finally, we uncover a novel role for
      Aurora-B regulated Astrin-SKAP complex in ensuring the correct plane of
      kinetochore-microtubule attachment. Thus, we identify Aurora-B as a key upstream
      regulator of end-on conversion in human cells and establish a late role for
      Astrin-SKAP complex in the end-on conversion process.Human chromosomes are
      captured along microtubule walls and then tethered to microtubule-ends through a
      multi-step end-on conversion process. Here the authors show that Aurora-B
      regulates end-on conversion in human cells and establish a late role for Astrin
      SKAP complex in the end-on conversion process.

PMID- 28751711
TI  - Evidence linking microRNA suppression of essential prosurvival genes with
      hippocampal cell death after traumatic brain injury.
AB  - The underlying molecular mechanisms of how dysregulated microRNAs (miRNAs) cause
      neurodegeneration after traumatic brain injury (TBI) remain elusive. Here we
      analyzed the biological roles of approximately 600 genes - we previously found
      these dysregulated in dying and surviving rat hippocampal neurons - that are
      targeted by ten TBI-altered miRNAs. Bioinformatic analysis suggests that
      neurodegeneration results from a global miRNA-mediated suppression of genes
      essential for maintaining proteostasis; many are hub genes - involved in RNA
      processing, cytoskeletal metabolism, intracellular trafficking, cell cycle
      progression, repair/maintenance, bioenergetics and cell-cell signaling - whose
      disrupted expression is linked to human disease. Notably, dysregulation of these
      essential genes would significantly impair synaptic function and functional brain
      connectivity. In surviving neurons, upregulated miRNA target genes are co
      regulated members of prosurvival pathways associated with cellular regeneration,
      neural plasticity, and development. This study captures the diversity of miRNA
      regulated genes that may be essential for cell repair and survival responses
      after TBI.

PMID- 28751712
TI  - Activation of mitophagy leads to decline in Mfn2 and loss of mitochondrial mass
      in Fuchs endothelial corneal dystrophy.
AB  - Human corneal endothelial cells (HCEnCs) are terminally differentiated cells that
      have limited regenerative potential. The large numbers of mitochondria in HCEnCs
      are critical for pump and barrier function required for corneal hydration and
      transparency. Fuchs Endothelial Corneal Dystrophy (FECD) is a highly prevalent
      late-onset oxidative stress disorder characterized by progressive loss of HCEnCs.
      We previously reported increased mitochondrial fragmentation and reduced ATP and
      mtDNA copy number in FECD. Herein, carbonyl cyanide m-chlorophenyl hydrazone
      (CCCP)-induced mitochondrial depolarization decreased mitochondrial mass and Mfn2
      levels, which were rescued with mitophagy blocker, bafilomycin, in FECD.
      Moreover, electron transport chain complex (I, V) decrease in FECD indicated
      deficient mitochondrial bioenergetics. Transmission electron microscopy of FECD
      tissues displayed an increased number of autophagic vacuoles containing
      degenerated and swollen mitochondria with cristolysis. An elevation of LC3-II and
      LAMP1 and downregulation of Mfn2 in mitochondrial fractions suggested that loss
      of fusion capacity targets fragmented mitochondria to the pre-autophagic pool and
      upregulates mitophagy. CCCP-induced mitochondrial fragmentation leads to Mfn2 and
      LC3 co-localization without activation of proteosome, suggesting a novel Mfn2
      degradation pathway via mitophagy. These data indicate constitutive activation of
      mitophagy results in reduction of mitochondrial mass and abrogates cellular
      bioenergetics during degeneration of post-mitotic cells of ocular tissue.

PMID- 28751713
TI  - From powders to bulk metallic glass composites.
AB  - One way to adjust the properties of materials is by changing its microstructure.
      This concept is not easily applicable on bulk metallic glasses (BMGs), because
      they do not consist of grains or different phases and so their microstructure is
      very homogeneous. One obvious way to integrate inhomogeneities is to produce bulk
      metallic glass composites (BMGCs). Here we show how to generate BMGCs via high
      pressure torsion (HPT) starting from powders (amorphous Zr-MG and crystalline
      Cu). Using this approach, the composition can be varied and by changing the
      applied shear strains, the refinement of the microstructure is adjustable. This
      process permits to produce amorphous/crystalline composites where the scale of
      the phases can be varied from the micro- to the nanometer regime. Even mixing of
      the two phases and the generation of new metallic glasses can be achieved. The
      refinement of microstructure increases the hardness and a hardness higher than
      the initial BMG can be obtained.

PMID- 28751714
TI  - A pilot study demonstrating the altered gut microbiota functionality in stable
      adults with Cystic Fibrosis.
AB  - Cystic Fibrosis (CF) and its treatment result in an altered gut microbiota
      composition compared to non-CF controls. However, the impact of this on gut
      microbiota functionality has not been extensively characterised. Our aim was to
      conduct a proof-of-principle study to investigate if measurable changes in gut
      microbiota functionality occur in adult CF patients compared to controls.
      Metagenomic DNA was extracted from faecal samples from six CF patients and six
      non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq
      platform. Metabolomic analysis using gas chromatography-mass spectrometry was
      conducted on faecal water. The gut microbiota of the CF group was significantly
      different compared to the non-CF controls, with significantly increased
      Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher
      pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated
      fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430
      meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared
      to the controls. Significant differences in metabolites occurred between the two
      groups. This proof-of-principle study demonstrates that measurable changes in gut
      microbiota functionality occur in CF patients compared to controls. Larger
      studies are thus needed to interrogate this further.

PMID- 28751715
TI  - In vitro significance of SOCS-3 and SOCS-4 and potential mechanistic links to
      wound healing.
AB  - Wound healing and the management of chronic wounds represent a significant burden
      on the NHS. Members of the suppressor of cytokine signalling (SOCS) family have
      been implicated in the regulation of a range of cellular processes. The current
      study aims to explore the importance of SOCS-3 and SOCS-4 in regulating cellular
      traits associated with wound healing. SOCS-3 over-expression and SOCS-4 knockdown
      mutant lines were generated and verified using q-PCR and western blotting in
      human keratinocytes (HaCaT) and endothelial cells (HECV). Over-expression of SOCS
      3 resulted in a significantly reduced proliferative rate in HaCaT keratinocytes
      and also enhanced the tubule formation capacity of HECV cells. SOCS-4 knockdown
      significantly reduced HaCaT migration and HECV cell tubule formation. Suppression
      of SOCS-4 influenced the responsiveness of HaCaT and HECV cells to EGF and
      TGFbeta and resulted in a dysregulation of phospho-protein expression in HaCaT
      cells. SOCS-3 and SOCS-4 appear to play regulatory roles in a number of
      keratinocyte and endothelial cellular traits associated with the wound healing
      process and may also be able to regulate the responsiveness of these cells to EGF
      and TGFbeta. This implies a potential regulatory role in the wound healing
      process and, thus highlights their potential as novel therapies.

PMID- 28751716
TI  - Static Magnetic Field Stimulation Enhances Oligodendrocyte Differentiation and
      Secretion of Neurotrophic Factors.
AB  - The cellular-level effects of low/high frequency oscillating magnetic field on
      excitable cells such as neurons are well established. In contrast, the effects of
      a homogeneous, static magnetic field (SMF) on Central Nervous System (CNS) glial
      cells are less investigated. Here, we have developed an in vitro SMF stimulation
      set-up to investigate the genomic effects of SMF exposure on oligodendrocyte
      differentiation and neurotrophic factors secretion. Human oligodendrocytes
      precursor cells (OPCs) were stimulated with moderate intensity SMF (0.3 T) for a
      period of two weeks (two hours/day). The differential gene expression of cell
      activity marker (c-fos), early OPC (Olig1, Olig2. Sox10), and mature
      oligodendrocyte markers (CNP, MBP) were quantified. The enhanced myelination
      capacity of the SMF stimulated oligodendrocytes was validated in a dorsal root
      ganglion microfluidics chamber platform. Additionally, the effects of SMF on the
      gene expression and secretion of neurotrophic factors- BDNF and NT3 was
      quantified. We also report that SMF stimulation increases the intracellular
      calcium influx in OPCs as well as the gene expression of L-type channel subunits
      CaV1.2 and CaV1.3. Our findings emphasize the ability of glial cells such as OPCs
      to positively respond to moderate intensity SMF stimulation by exhibiting
      enhanced differentiation, functionality as well as neurotrophic factor release.

PMID- 28751717
TI  - Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain.
AB  - Mutations in the GDAP1 gene can cause Charcot-Marie-Tooth disease. These
      mutations are quite rare in most Western countries but not so in certain regions
      of Spain or other Mediterranean countries. This cross-sectional retrospective
      multicenter study analyzed the clinical and genetic characteristics of patients
      with GDAP1 mutations across Spain. 99 patients were identified, which were
      distributed across most of Spain, but especially in the Northwest and
      Mediterranean regions. The most common genotypes were p.R120W (in 81% of patients
      with autosomal dominant inheritance) and p.Q163X (in 73% of autosomal recessive
      patients). Patients with recessively inherited mutations had a more severe
      phenotype, and certain clinical features, like dysphonia or respiratory
      dysfunction, were exclusively detected in this group. Dominantly inherited
      mutations had prominent clinical variability regarding severity, including 29% of
      patients who were asymptomatic. There were minor clinical differences between
      patients harboring specific mutations but not when grouped according to
      localization or type of mutation. This is the largest clinical series to date of
      patients with GDAP1 mutations, and it contributes to define the genetic
      distribution and genotype-phenotype correlation in this rare form of CMT.

PMID- 28751718
TI  - Two mouse models reveal an actionable PARP1 dependence in aggressive chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) remains an incurable disease. Two recurrent
      cytogenetic aberrations, namely del(17p), affecting TP53, and del(11q), affecting
      ATM, are associated with resistance against genotoxic chemotherapy (del17p) and
      poor outcome (del11q and del17p). Both del(17p) and del(11q) are also associated
      with inferior outcome to the novel targeted agents, such as the BTK inhibitor
      ibrutinib. Thus, even in the era of targeted therapies, CLL with alterations in
      the ATM/p53 pathway remains a clinical challenge. Here we generated two mouse
      models of Atm- and Trp53-deficient CLL. These animals display a significantly
      earlier disease onset and reduced overall survival, compared to controls. We
      employed these models in conjunction with transcriptome analyses following
      cyclophosphamide treatment to reveal that Atm deficiency is associated with an
      exquisite and genotype-specific sensitivity against PARP inhibition. Thus, we
      generate two aggressive CLL models and provide a preclinical rational for the use
      of PARP inhibitors in ATM-affected human CLL.ATM and TP53 mutations are
      associated with poor prognosis in chronic lymphocytic leukaemia (CLL). Here the
      authors generate mouse models of Tp53- and Atm-defective CLL mimicking the high
      risk form of human disease and show that Atm-deficient CLL is sensitive to PARP1
      inhibition.

PMID- 28751719
TI  - Identification of non-activated lymphocytes using three-dimensional refractive
      index tomography and machine learning.
AB  - Identification of lymphocyte cell types are crucial for understanding their
      pathophysiological roles in human diseases. Current methods for discriminating
      lymphocyte cell types primarily rely on labelling techniques with magnetic beads
      or fluorescence agents, which take time and have costs for sample preparation and
      may also have a potential risk of altering cellular functions. Here, we present
      the identification of non-activated lymphocyte cell types at the single-cell
      level using refractive index (RI) tomography and machine learning. From the
      measurements of three-dimensional RI maps of individual lymphocytes, the
      morphological and biochemical properties of the cells are quantitatively
      retrieved. To construct cell type classification models, various statistical
      classification algorithms are compared, and the k-NN (k = 4) algorithm was
      selected. The algorithm combines multiple quantitative characteristics of the
      lymphocyte to construct the cell type classifiers. After optimizing the feature
      sets via cross-validation, the trained classifiers enable identification of three
      lymphocyte cell types (B, CD4+ T, and CD8+ T cells) with high sensitivity and
      specificity. The present method, which combines RI tomography and machine
      learning for the first time to our knowledge, could be a versatile tool for
      investigating the pathophysiological roles of lymphocytes in various diseases
      including cancers, autoimmune diseases, and virus infections.

PMID- 28751720
TI  - Experimental estimation and analysis of variance of the measured loss power of
      magnetic nanoparticles.
AB  - Magnetic nanoparticles dissipate heat when exposed to alternating magnetic fields
      (AMFs), making them suitable for cancer hyperthermia. Therapeutic heating
      applications demand accurate characterization of the heating power dissipated by
      the particles. Specific loss power (SLP) generated by magnetic nanoparticles is
      estimated from calorimetric heating measurements. Such measurements require
      adiabatic conditions, yet they are typically performed in an AMF device with non
      adiabatic conditions. We have measured heating from four magnetic nanoparticle
      constructs using a range of frequencies (150-375 kHz) and magnetic fields (4-44
      kA/m). We have extended a method developed to estimate SLP from the inherently
      non-adiabatic measurements, where we identify data ranges that conform to (quasi)
      adiabatic conditions. Each time interval of measurement that met a predetermined
      criterion was used to generate a value of SLP, and the mean from all estimates
      was selected as the estimated SLP. Despite the application of rigorous selection
      criteria, measured temperature data displayed variability at specific heating
      loads resulting in larger variance of calculated mean SLP values. Overall, the
      results show a linear dependence of the SLP with AMF frequency, as anticipated by
      current models. Conversely, measured amplitude-dependent SLP profiles of all
      studied constructs conform to no predictions of current models.

PMID- 28751721
TI  - Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis.
AB  - Megakaryocytopoiesis is a complex differentiation process driven by the hormone
      thrombopoietin by which haematopoietic progenitor cells give rise to
      megakaryocytes, the giant bone marrow cells that in turn break down to form blood
      platelets. The Tribbles Pseudokinase 3 gene (TRIB3) encodes a pleiotropic protein
      increasingly implicated in the regulation of cellular differentiation programmes.
      Previous studies have hinted that TRIB3 could be also involved in
      megakaryocytopoiesis but its role in this process has so far not been
      investigated. Using cellular model systems of haematopoietic lineage
      differentiation here we demonstrate that TRIB3 is a negative modulator of
      megakaryocytopoiesis. We found that in primary cultures derived from human
      haematopoietic progenitor cells, thrombopoietin-induced megakaryocytic
      differentiation led to a time and dose-dependent decrease in TRIB3 mRNA levels.
      In the haematopoietic cell line UT7/mpl, silencing of TRIB3 increased basal and
      thrombopoietin-stimulated megakaryocyte antigen expression, as well as basal
      levels of ERK1/2 phosphorylation. In primary haematopoietic cell cultures,
      silencing of TRIB3 facilitated megakaryocyte differentiation. In contrast, over
      expression of TRIB3 in these cells inhibited the differentiation process. The in
      vitro identification of TRIB3 as a negative regulator of megakaryocytopoiesis
      suggests that in-vivo this gene could be important for the regulation of platelet
      production.

PMID- 28751722
TI  - Hepatocyte specific TIMP3 expression prevents diet dependent fatty liver disease
      and hepatocellular carcinoma.
AB  - Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of
      conditions, ranging from non-progressive bland steatosis to hepatocarcinoma.
      Tissue inhibitor of metalloproteinase 3 (Timp3) has a role in the pathogenesis of
      fatty liver disease associated with obesity and is silenced during metabolic
      disorders and liver cancer. We generated an hepatocyte-specific TIMP3 'gain-of
      function' mouse model under the control of the Albumin promoter (AlbT3) and
      investigated its effects during high-fat diet (HFD). After 16 weeks of HFD, TIMP3
      overexpression significantly improved glucose metabolism, hepatic fatty acid
      oxidation and cholesterol homeostasis. In AlbT3 mice CYP7A1, MDR3 and MRP2 gene
      expressions were observed, consistent with higher bile acid synthesis and export.
      Next, to evaluate the role of A Disintegrin and Metalloproteinase 17 (ADAM17), a
      crucial target of TIMP3, in these processes, we created mice deficient in Adam17
      specifically in hepatocyte (A17LKO) or in myeloid lineage (A17MKO), founding that
      only A17LKO showed improvement in liver steatosis induced by HFD. Moreover, both,
      AlbT3 and A17LKO significantly reduced diethylnitrosamine-initiated, HFD-promoted
      hepatic tumorigenesis assessed by tumor multiplicity and total tumor area. Taken
      together, these data indicate that hepatic TIMP3 can slow progression of NAFLD,
      and tumorigenesis, at least in part, through the regulation of ADAM17 activity.

PMID- 28751723
TI  - Hydrogen sulphide donors selectively potentiate a green tea polyphenol EGCG
      induced apoptosis of multiple myeloma cells.
AB  - Hydrogen sulphide (H2S) is a colourless gas with the odour of rotten eggs and has
      recently been recognized as a signal mediator in physiological activities related
      with the regulation of homeostasis, the vascular system and the inflammatory
      system. Here we show that H2S donors, including sodium hydrogen sulphide (NaHS),
      GYY 4137 and diallyltrisulfide (DATS), synergistically enhanced the anti-cancer
      effect of a green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) against
      multiple myeloma cells without affecting normal cells. NaHS significantly
      potentiated the anti-cancer effect of EGCG and prolonged survival in a mouse
      xenograft model. In this mechanism, H2S enhanced apoptotic cell death through
      cyclic guanosine monophosphate (cGMP)/acid sphingomyelinase pathway induced by
      EGCG. Moreover, NaHS reduced the enzyme activity of cyclic nucleotide
      phosphodiesterase that is known as cGMP negative regulator. In conclusion, we
      identified H2S as a gasotransmitter that potentiates EGCG-induced cancer cell
      death.

PMID- 28751724
TI  - Values of ultrasound features and MMP-9 of papillary thyroid carcinoma in
      predicting cervical lymph node metastases.
AB  - Preoperative assessment of the cervical lymph node status is important in
      therapeutic schedule and further evaluations of prognosis for papillary thyroid
      carcinoma (PTC) patients. Our aim was to investigate the diagnostic values of
      conventional ultrasound (US), contrast-enhanced ultrasound (CEUS) features and
      the expression of MMP-9 of PTC in predicting the cervical lymph node metastases
      (LNM). In total, 156 patients with PTC confirmed by surgical pathology were
      included. Seventy-one patients had cervical LNM, while 85 patients had no LNM.
      The patients had cervical LNM (39.51 +/- 13.29 years) were younger than those had
      no LNM (44.15 +/- 10.94 years) (P = 0.02). Multivariate logistic regression
      results showed that tumor size >=0.95 cm (OR = 13.47), ill-defined margin (OR =
      4.31), internal heterogeneous low-enhancement (OR = 5.19) and ECE (OR = 25.25)
      were predictive for the presence of cervical LNM. The detection rate of ECE for
      the PTC with LNM by CEUS (81.48%, 44/54) was higher than by US (46.30%, 25/54).
      There was significant difference in MMP-9 intensity between PTC with and without
      cervical LNM (P = 0.000), and intense reactions (+++) were mainly found in the
      PTCs with LNM (80.95%, 17/21). In conclusion, the combination of conventional US,
      CEUS features and MMP-9 expression may serve as an effective tool for predicting
      the cervical LNM of PTC.

PMID- 28751725
TI  - Image based modeling of bleb site selection.
AB  - Cells often employ fast, pressure-driven blebs to move through tissues or against
      mechanical resistance, but how bleb sites are selected and directed to the cell
      front remains an open question. Previously, we found that chemotaxing
      Dictyostelium cells preferentially bleb from concave regions, where membrane
      tension facilitates membrane-cortex detachment. Now, through a novel modeling
      approach based on actual cell contours, we use cell geometry to predict where
      blebs will form in migrating cells. We find that cell geometry alone, and by
      implication, physical forces in the membrane, is sufficient to predict the
      location of blebs in rounded cells moving in a highly resistive environment. The
      model is less successful with more polarized cells moving against less
      resistance, but can be greatly improved by positing a front-to-back gradient in
      membrane-cortex adhesion. In accord with this prediction, we find that Talin,
      which links membrane and cortex, forms such a front-to-back gradient. Thus our
      model provides a means of dissecting out the role of physical forces in
      controlling where blebs form, and shows that in certain circumstances they could
      be the major determining factor.

PMID- 28751726
TI  - Shockwave-Loading-Induced Enhancement of T c in Superconducting
      Bi2Sr2CaCu2O8+delta.
AB  - We report a shockwave method for altering the properties of the superconductor
      material Bi2Sr2CaCu2O8+delta (Bi2212). We find that the superconducting
      transition temperature (T c) increases from 84 K for the pristine sample to 94 K
      for the sample treated at a temperature and pressure of ~1200 K and ~31 GPa,
      respectively. X-ray diffraction and transmission electron microscopy
      characterizations indicate that this T c enhancement arises from a phase
      transition from pristine Bi2212 to a mixture of superconducting Bi2212 and
      semiconducting Bi2Sr2CuO6+delta (Bi2201) during the shockwave treatment. The
      shockwave-treated sample exhibits n-type semiconductor properties (with an on-off
      ratio ~5), in contrast to the pure metallic pristine sample. Our study offers an
      alternative route for modifying the superconducting properties via a shockwave
      treatment. Furthermore, this method may provide a new approach for studying other
      temperature- and pressure-sensitive materials.

PMID- 28751727
TI  - Temporal trend of hepatitis B surface mutations in the post-immunization period:
      9 years of surveillance (2005-2013) in eastern China.
AB  - Limited information is available about the temporal trend in the prevalence and
      evolution of hepatitis B virus (HBV) S-gene mutations in the post-immunization
      era in China. From 2005 to 2013, 1077 hepatitis B cases under 15 years of age
      reported through Chinese National Notifiable Disease Reporting System (NNDRS)
      were successfully sequenced of S-gene in Shandong province, China. A total of 97
      (9.01%) cases had amino acid (aa) substitution in the "alpha" determinant of
      HBsAg. The yearly prevalence from 2005 to 2013 maintained at a relatively stable
      level, and showed no significant change (P > 0.05). Multivariate logistic
      regression analysis demonstrated that the prevalence of "alpha" mutations was
      independently associated with the maternal HBsAg status (P < 0.05), and not with
      surveillance year and hepatitis B vaccination (P > 0.05). The hottest mutation
      position was aa126 (I126S/N and T126A, 29.63%), and aa 145 (G145R/A, 25.93%).
      Mutated residue 126 tended to occur less frequent, while that of residue 145 was
      more frequent with increasing year. Our data showed that there was no increase in
      the frequency of HBV "alpha" mutations over time during the post-immunization
      period. However, long-term vaccination might enhance the change of HBV mutational
      pattern, and G145 mutation was becoming dominant.

PMID- 28751728
TI  - Radiocesium concentrations in wild mushrooms after the accident at the Fukushima
      Daiichi Nuclear Power Station: Follow-up study in Kawauchi village.
AB  - Since the accident at the Chernobyl Nuclear Power Plant, it has become well known
      that radiocesium tends to concentrate in wild mushrooms. During the recovery
      process after the accident at the Fukushima Daiichi Nuclear Power Station
      (FDNPS), it is important to perform follow-up measurements of the activity
      concentrations of radiocesium in mushrooms. We evaluated the activity
      concentrations of the detected artificial radionuclides (radiocesium) in wild
      mushrooms collected from Kawauchi village, which is within 30 km of the FDNPS, in
      2015, four years after the accident. We found that the radiocesium was determined
      in 147 of 159 mushroom samples (92.4%). Based on the average mushroom consumption
      of Japanese citizens (6.28 kg per year), we calculated committed effective doses
      ranging from <0.001 to 0.6 mSv. Although committed effective doses are relatively
      limited, even if residents have consumed mushrooms several times, continuous
      monitoring of the radiocesium in mushrooms in Fukushima is needed for sustained
      recovery from the nuclear disaster.

PMID- 28751729
TI  - High resolution temporal transcriptomics of mouse embryoid body development
      reveals complex expression dynamics of coding and noncoding loci.
AB  - Cellular responses to stimuli are rapid and continuous and yet the vast majority
      of investigations of transcriptional responses during developmental transitions
      typically use long interval time courses; limiting the available interpretive
      power. Moreover, such experiments typically focus on protein-coding transcripts,
      ignoring the important impact of long noncoding RNAs. We therefore evaluated
      coding and noncoding expression dynamics at unprecedented temporal resolution (6
      hourly) in differentiating mouse embryonic stem cells and report new insight into
      molecular processes and genome organization. We present a highly resolved
      differentiation cascade that exhibits coding and noncoding transcriptional
      alterations, transcription factor network interactions and alternative splicing
      events, little of which can be resolved by long-interval developmental time
      courses. We describe novel short lived and cycling patterns of gene expression
      and dissect temporally ordered gene expression changes in response to
      transcription factors. We elucidate patterns in gene co-expression across the
      genome, describe asynchronous transcription at bidirectional promoters and
      functionally annotate known and novel regulatory lncRNAs. These findings
      highlight the complex and dynamic molecular events underlying mammalian
      differentiation that can only be observed though a temporally resolved time
      course.

PMID- 28751730
TI  - Test-retest reproducibility of cardiac magnetic resonance imaging in healthy mice
      at 7-Tesla: effect of anesthetic procedures.
AB  - Cardiac magnetic resonance (CMR) has emerged as a powerful tool for in vivo
      assessments of cardiac parameters in experimental animal models of cardiovascular
      diseases, but its reproducibility in this setting remains poorly explored. To
      address this issue, we investigated the test-retest reproducibility of
      preclinical cardiac magnetic resonance imaging (CMR) at 7 Tesla in healthy
      C57BL/6 mice, including an analysis of the impact of different anesthetic
      procedures (isoflurane or pentobarbital). We also analyzed the intra-study
      reproducibility and the intra- and inter-observer post-processing reproducibility
      of CMR images. Test-retest reproducibility was high for left ventricular
      parameters, especially with the isoflurane anesthetic procedure, whereas right
      ventricular parameters and deformation measurements were less reproducible,
      mainly due to physiological variability. Post-processing reproducibility of CMR
      images was high both within and between observers. These results highlight that
      anesthetic procedures might influence CMR test-retest reproducibility, an
      important ethical consideration for longitudinal studies in rodent models of
      cardiomyopathy to limit the number of animals used.

PMID- 28751731
TI  - Construction of porous CuCo2S4 nanorod arrays via anion exchange for high
      performance asymmetric supercapacitor.
AB  - To push the energy density limit of supercapacitors, proper pseudocapacitive
      materials with favorable nanostructures are urgently pursued. Ternary transition
      metal sulfides are promising electrode materials due to the better conductivity
      and higher electrochemical activity in comparison to the single element sulfides
      and transition metal oxides. In this work, we have successfully synthesized
      porous CuCo2S4 nanorod array (NRAs) on carbon textile through a stepwise
      hydrothermal method, including the growth of the Cu-Co precursor nanowire arrays
      and subsequent conversion into CuCo2S4 NRAs via anion exchange reaction. The
      CuCo2S4 NRAs electrode exhibits a greatly enhanced specific capacitance and an
      outstanding cycling stability. Moreover, an asymmetric supercapacitor using the
      CuCo2S4 NRAs as positive electrode and activated carbon as negative electrode
      delivers a high energy density of 56.96 W h kg-1. Such superior performance
      demonstrate that the CuCo2S4 NRAs are promising materials for future energy
      storage applications.

PMID- 28751732
TI  - Natural variations in the biofilm-associated protein BslA from the genus
      Bacillus.
AB  - BslA is a protein secreted by Bacillus subtilis which forms a hydrophobic film
      that coats the biofilm surface and renders it water-repellent. We have
      characterised three orthologues of BslA from Bacillus amyloliquefaciens, Bacillus
      licheniformis and Bacillus pumilus as well as a paralogue from B. subtilis called
      YweA. We find that the three orthologous proteins can substitute for BslA in B.
      subtilis and confer a degree of protection, whereas YweA cannot. The degree to
      which the proteins functionally substitute for native BslA correlates with their
      in vitro biophysical properties. Our results demonstrate the use of naturally
      evolved variants to provide a framework for teasing out the molecular basis of
      interfacial self-assembly.

PMID- 28751733
TI  - "High-Throughput Characterization of Region-Specific Mitochondrial Function and
      Morphology".
AB  - The tissue-specific etiology of aging and stress has been elusive due to
      limitations in data processing of current techniques. Despite that many
      techniques are high-throughput, they usually use singular features of the data
      (e.g. whole fluorescence). One technology at the nexus of fluorescence-based
      screens is large particle flow cytometry ("biosorter"), capable of recording
      positional fluorescence and object granularity information from many individual
      live animals. Current processing of biosorter data, however, do not integrate
      positional information into their analysis and data visualization. Here, we
      present a bioanalytical platform for the quantification of positional information
      ("longitudinal profiling") of C. elegans, which we posit embodies the benefits of
      both high-throughput screening and high-resolution microscopy. We show the use of
      these techniques in (1) characterizing distinct responses of a transcriptional
      reporter to various stresses in defined anatomical regions, (2) identifying
      regions of high mitochondrial membrane potential in live animals, (3) monitoring
      regional mitochondrial activity in aging models and during development, and (4)
      screening for regulators of muscle mitochondrial dynamics in a high-throughput
      format. This platform offers a significant improvement in the quality of high
      throughput biosorter data analysis and visualization, opening new options for
      region-specific phenotypic screening of complex physiological phenomena and
      mitochondrial biology.

PMID- 28751734
TI  - Glucocorticoid therapy regulates podocyte motility by inhibition of Rac1.
AB  - Nephrotic syndrome (NS) occurs when the glomerular filtration barrier becomes
      excessively permeable leading to massive proteinuria. In childhood NS, immune
      system dysregulation has been implicated and increasing evidence points to the
      central role of podocytes in the pathogenesis. Children with NS are typically
      treated with an empiric course of glucocorticoid (Gc) therapy; a class of
      steroids that are activating ligands for the glucocorticoid receptor (GR)
      transcription factor. Although Gc-therapy has been the cornerstone of NS
      management for decades, the mechanism of action, and target cell, remain poorly
      understood. We tested the hypothesis that Gc acts directly on the podocyte to
      produce clinically useful effects without involvement of the immune system. In
      human podocytes, we demonstrated that the basic GR-signalling mechanism is intact
      and that Gc induced an increase in podocyte barrier function. Defining the GR
      cistrome identified Gc regulation of motility genes. These findings were
      functionally validated with live-cell imaging. We demonstrated that treatment
      with Gc reduced the activity of the pro-migratory small GTPase regulator Rac1.
      Furthermore, Rac1 inhibition had a direct, protective effect on podocyte barrier
      function. Our studies reveal a new mechanism for Gc action directly on the
      podocyte, with translational relevance to designing new selective synthetic Gc
      molecules.

PMID- 28751735
TI  - Aggregated transthyretin is specifically packaged into placental nano-vesicles in
      preeclampsia.
AB  - In preeclampsia, the serum levels of transthyretin, a carrier protein for
      thyroxine, are elevated. Transthyretin isolated from preeclamptic serum is also
      aggregated and can induce preeclampsia-like symptoms in pregnant IL10-/- mice.
      Using western blotting, immunofluorescence, ELISA and qRT-PCR, we investigated
      the production of transthyretin by preeclamptic placentae and whether
      transthyretin is carried into the maternal circulation via placental
      extracellular vesicles. Both total and aggregated transthyretin were present in
      higher levels in preeclamptic placentae compared to normotensive placentae (p <
      0.05, n = 7), however the levels of transythretin mRNA were not significantly
      different (n = 8). Preeclamptic placentae secreted similar levels of total
      transthyretin compared to normotensive placentae (2352 +/- 2949 ng/mL vs. 3250 +/
      1864 ng/mL, mean +/- SD, p > 0.05, n = 8), however in preeclampsia, a
      significant proportion is vesicle-associated (~48% vs 0%). Increased levels of
      aggregated transthyretin were specifically associated to preeclamptic nano
      vesicles (p < 0.02, n = 8). This study showed that the placenta actively produces
      transthyretin and in preeclampsia, a significant amount is extruded into the
      maternal circulation via placental exracellular vesicles. The increased
      aggregation of transthyretin in preeclampsia occurs at the post-transcriptional
      level and while preeclamptic nano-vesicles may be removing a toxic aggregated
      protein from the placenta, they may also be delivering aggregated transthyretin
      to specific maternal organs, contributing to the pathogenesis of preeclampsia.

PMID- 28751736
TI  - Selective dual-band metamaterial perfect absorber for infrared stealth
      technology.
AB  - We propose a dual-band metamaterial perfect absorber with a metal-insulator-metal
      structure (MIM) for use in infrared (IR) stealth technology. We designed the MIM
      structure to have surface plasmon polariton (SPP) and magnetic polariton (MP)
      resonance peaks at 1.54 MUm and 6.2 MUm, respectively. One peak suppresses the
      scattering signals used by laser-guided missiles, and the other matches the
      atmospheric absorption band, thereby enabling the suppression of long-wavelength
      IR (LWIR) and mid-wavelength IR (MWIR) signals from objects as they propagate
      through the air. We analysed the spectral properties of the resonance peaks by
      comparing the wavelength of the MP peak calculated using the finite-difference
      time-domain method with that obtained by utilizing an inductor-capacitor circuit
      model. We evaluated the dependence of the performance of the dual-band
      metamaterial perfect absorber on the incident angle of light at the surface. The
      proposed absorber was able to reduce the scattering of 1.54 MUm IR laser light by
      more than 90% and suppress the MWIR and LWIR signatures by more than 92%, as well
      as maintain MWIR and LWIR signal reduction rates greater than 90% across a wide
      temperature range from room temperature to 500  degrees C.

PMID- 28751737
TI  - Elucidation of the biosynthetic pathway of cis-jasmone in Lasiodiplodia
      theobromae.
AB  - In plants, cis-jasmone (CJ) is synthesized from alpha-linolenic acid (LA) via two
      biosynthetic pathways using jasmonic acid (JA) and iso-12-oxo-phytodienoic acid
      (iso-OPDA) as key intermediates. However, there have been no reports documenting
      CJ production by microorganisms. In the present study, the production of fungal
      derived CJ by Lasiodiplodia theobromae was observed for the first time, although
      this production was not observed for Botrytis cinerea, Verticillium longisporum,
      Fusarium oxysporum, Gibberella fujikuroi, and Cochliobolus heterostrophus. To
      investigate the biosynthetic pathway of CJ in L. theobromae, administration
      experiments using [18,18,18-2H3, 17,17-2H2]LA (LA-d5), [18,18,18-2H3, 17,17
      2H2]12-oxo-phytodienoic acid (cis-OPDA-d5), [5',5',5'-2H3, 4',4'-2H2, 3'-2H1]OPC
      8:0 (OPC8-d6), [5',5',5'-2H3, 4',4'-2H2, 3'-2H1]OPC 6:0 (OPC6-d6), [5',5',5'-2H3,
      4',4'-2H2, 3'-2H1]OPC 4:0 (OPC4-d6), and [11,11-2H2, 10,10-2H2, 8,8-2H2, 2,2
      2H2]methyl iso-12-oxo-phytodienoate (iso-MeOPDA-d8) were carried out, revealing
      that the fungus produced CJ through a single biosynthetic pathway via iso-OPDA.
      Interestingly, it was suggested that the previously predicted decarboxylation
      step of 3,7-didehydroJA to afford CJ might not be involved in CJ biosynthesis in
      L. theobromae.

PMID- 28751738
TI  - ApoE Influences the Blood-Brain Barrier Through the NF-kappaB/MMP-9 Pathway After
      Traumatic Brain Injury.
AB  - Apolipoprotein E (ApoE), encoded by the ApoE gene (APOE), influences the outcomes
      of traumatic brain injury (TBI), but the mechanism remains unclear. The present
      study aimed to investigate the effects of different ApoEs on the outcome of TBI
      and to explore the possible mechanisms. Controlled cortical impact (CCI) was
      performed on APOEepsilon3 (E3) and APOEepsilon4 (E4) transgenic mice, APOE-KO
      (KO) mice, and wild type (WT) mice to construct an in vivo TBI model.
      Neurological deficits, blood brain barrier (BBB) permeability and brain edema
      were detected at days 1, 3, and 7 after TBI. The results revealed no significant
      differences among the four groups at day 1 or day 3 after injury, but more severe
      deficits were found in E4 and KO mice than in E3 and WT mice. Furthermore, a
      significant loss of tight junction proteins was observed in E4 and KO mice
      compared with E3 and WT mice at day 7. Additionally, more expression and
      activation of NF-kappaB and MMP-9 were found in E4 mice compared with E3 mice.
      Different ApoEs had distinct effects on neuro-function and BBB integrity after
      TBI. ApoE3, but not E4, might inhibit the NF-kappaB/MMP-9 pathway to alleviate
      BBB disruption and improve TBI outcomes.

PMID- 28751739
TI  - Distinct brain responses to different inhibitions: Evidence from a modified
      Flanker Task.
AB  - Whether inhibition is a unitary or multifaceted construct is still an open
      question. To clarify the electrophysiological distinction among the different
      types of inhibition, we used a modified flanker paradigm, in which interference
      inhibition, rule inhibition, and response inhibition were compared to non
      inhibition condition. The results indicated that, compared to the non-inhibition
      condition (1) the interference inhibition condition induced larger negativities
      during N2 epoch at the frontal region, (2) the rule inhibition condition elicited
      a larger N1 at the posterior region, followed by a larger P3a at the frontal
      region, reflecting the function of proactive cognitive control in the new
      stimulus-reaction (S-R) association, and (3) the response inhibition condition
      evoked a larger P3b at the posterior region, reflecting the process of
      suppressing the old response and reprogramming the new action. These findings
      provide new evidence that distinct neural mechanisms underlie different types of
      inhibition.

PMID- 28751740
TI  - 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and
      metastasis of breast carcinoma in mice.
AB  - Metastasis causes approximately 90% of breast cancer-related deaths in women.
      Previously, we have demonstrated that 2-dodecyl-6-methoxycyclohexa-2,5-diene- 1,4
      dione (DMDD) remarkably inhibited the growth of human breast cancer cells with
      little toxicity. In this study, we investigated the toxicity and efficacy of DMDD
      to treat metastatic breast tumors using an in vivo mouse model of the 4T1 mammary
      carcinoma. DMDD caused no observable toxicity and significantly extended the
      survival of 4T1 tumor-bearing mice. DMDD effectively inhibited the growth of 4T1
      cells in vitro, and suppressed the growth and metastasis of mammary tumor in
      vivo. The levels of inflammatory cytokines in the serum (TNF-alpha, IL-6, IL-12,
      TGF-beta, and VEGF) were down regulated by DMDD. Immunohistochemical analysis
      demonstrated that the inhibition of tumor growth and metastasis was associated
      with activation of Bax, cleaved caspases-3 and -9, and down-regulation of Bcl-2,
      MMP-2 and -9, NF-kappaB and IkappaBalpha. We speculate that DMDD inhibits
      cytokine production in the tumor cells in mice, which leads to deactivation of NF
      kappaB pathway, and consequently inhibits the expression of many anti-apoptosis
      and metastasis-promoting genes, such as Bcl-2 and MMPs. Collectively, our results
      demonstrate the potential of DMDD as a safe and effective antitumor agent in the
      treatment of late-stage breast cancer.

PMID- 28751741
TI  - Soil microbial community structure and catabolic activity are significantly
      degenerated in successive rotations of Chinese fir plantations.
AB  - This study examined the hypotheses that soil microbial community composition and
      catabolic activity would significantly degenerated by consecutive monoculture in
      Chinese fir plantations. The phospholipid fatty acids (PLFA) and community level
      physiological profiles (CLPP) methods were used to assess the variations of soil
      microbial community among the first rotation Chinese fir plantation (FCP), the
      second rotation plantation (SCP) and the third rotation plantation (TCP). The
      total content of PLFA biomarkers was highest in FCP, followed by SCP, and TCP was
      the least detected. Conversely, the fungi/bacteria ratio significantly increased
      in the SCP and TCP soils. The average well-color development (AWCD) values
      significantly decreased (FCP > SCP > TCP). However, the sum of AWCD values of
      amino acids, carboxylic acids and phenolic compounds were higher significantly in
      the SCP and TCP soils than FCP soils, suggesting that the microflora feeding on
      acids gradually became predominant in the continuous monoculture plantation
      soils. Soil C/N ratio was one of the most important factors to soil microbial
      diversity. Both the PLFA and CLPP results illustrated the long-term pure
      plantation pattern exacerbated the microecological imbalance in the rhizospheric
      soils of Chinese fir, and markedly decreased the soil microbial community
      diversity and metabolic activity.

PMID- 28751742
TI  - Fractal scaling of particle-size distribution and associations with soil
      properties of Mongolian pine plantations in the Mu Us Desert, China.
AB  - Mongolian pine plantations (MPPs) composed of Pinus sylvestris var. mongolica (P.
      sylvestris) are used for desertification control and restoration of degraded land
      in arid and semi-arid regions. We studied soil changes associated with P.
      sylvestris by comparing top (0-20 cm) and sub-top (20-40 cm) soil properties
      across 8 stand density gradients of MPPs ranging from 900 +/- 5-2700 +/- 50 trees
      ha-1. The study was conducted in the uncovered Sandy Land in the southern Mu Us
      Desert, China. The relationships between the volume fractal dimensions (D) of
      soil particle size distribution and soil physicochemical properties were
      evaluated. D was determined using a laser diffraction technique and soil
      properties were measured. In the top layer, P. sylvestris significantly
      positively affected soil physicochemical properties except for bulk density and
      total nitrogen. These effects were not observed in the sub-top soil layer. D
      values ranged from 1.52 +/- 0.29-2.08 +/- 0.06 and were significantly correlated
      with stand density. Significant correlations were observed between D and soil
      properties (except total nitrogen) in the top soil layer. Given these results, we
      concluded that D is a sensitive and useful index because it quantifies changes in
      soil properties that additionally implies desertification in the studied area.

PMID- 28751743
TI  - Anti-AMPA GluA3 antibodies in Frontotemporal dementia: a new molecular target.
AB  - Frontotemporal Dementia (FTD) is a neurodegenerative disorder mainly
      characterised by Tau or TDP43 inclusions. A co-autoimmune aetiology has been
      hypothesised. In this study, we aimed at defining the pathogenetic role of anti
      AMPA GluA3 antibodies in FTD. Serum and cerebrospinal fluid (CSF) anti-GluA3
      antibody dosage was carried out and the effect of CSF with and without anti-GluA3
      antibodies was tested in rat hippocampal neuronal primary cultures and in
      differentiated neurons from human induced pluripotent stem cells (hiPSCs). TDP43
      and Tau expression in hiPSCs exposed to CSF was assayed. Forty-one out of 175
      screened FTD sera were positive for the presence of anti-GluA3 antibodies
      (23.4%). FTD patients with anti-GluA3 antibodies more often presented presenile
      onset, behavioural variant FTD with bitemporal atrophy. Incubation of rat
      hippocampal neuronal primary cultures with CSF with anti-GluA3 antibodies led to
      a decrease of GluA3 subunit synaptic localization of the AMPA receptor (AMPAR)
      and loss of dendritic spines. These results were confirmed in differentiated
      neurons from hiPSCs, with a significant reduction of the GluA3 subunit in the
      postsynaptic fraction along with increased levels of neuronal Tau. In conclusion,
      autoimmune mechanism might represent a new potentially treatable target in FTD
      and might open new lights in the disease underpinnings.

PMID- 28751744
TI  - Laboratory-based X-ray phase-imaging scanner using Talbot-Lau interferometer for
      non-destructive testing.
AB  - An X-ray Talbot-Lau interferometer scanning setup consisting of three
      transmission gratings, a laboratory-based X-ray source that emits X-rays
      vertically, and an image detector on the top has been developed for the
      application of X-ray phase imaging to moving objects that cannot be tested
      clearly with conventional absorption contrast. The grating-based X-ray phase
      imaging method usually employs a phase-stepping (or fringe-scanning) technique by
      displacing one of the gratings step-by-step while the object stays still. Since
      this approach is not compatible with a scanner-type application for moving
      objects, we have developed a new algorithm for achieving the function of phase
      stepping without grating displacement. By analyzing the movie of the moire
      pattern as the object moves across the field of view, we obtain the absorption,
      differential phase, and visibility images. The feasibility of the X-ray phase
      imaging scanner has been successfully demonstrated for a long sample moving at 5
      mm/s. This achievement is a breakthrough for the practical industrial application
      of X-ray phase imaging for screening objects carried on belt-conveyers such as
      those in factories.

PMID- 28751745
TI  - Translational roles of the C75 2'OH in an in vitro tRNA transcript at the
      ribosomal A, P and E sites.
AB  - Aminoacyl-tRNAs containing a deoxy substitution in the penultimate nucleotide
      (C75 2'OH -> 2'H) have been widely used in translation for incorporation of
      unnatural amino acids (AAs). However, this supposedly innocuous modification
      surprisingly increased peptidyl-tRNAAlaugc drop off in biochemical assays of
      successive incorporations. Here we predict the function of this tRNA 2'OH in the
      ribosomal A, P and E sites using recent co-crystal structures of ribosomes and
      tRNA substrates and test these structure-function models by systematic kinetics
      analyses. Unexpectedly, the C75 2'H did not affect A- to P-site translocation nor
      peptidyl donor activity of tRNAAlaugc. Rather, the peptidyl acceptor activity of
      the A-site Ala-tRNAAlaugc and the translocation of the P-site deacylated
      tRNAAlaugc to the E site were impeded. Delivery by EF-Tu was not significantly
      affected. This broadens our view of the roles of 2'OH groups in tRNAs in
      translation.

PMID- 28751746
TI  - Extreme Quantum Advantage when Simulating Classical Systems with Long-Range
      Interaction.
AB  - Classical stochastic processes can be generated by quantum simulators instead of
      the more standard classical ones, such as hidden Markov models. One reason for
      using quantum simulators has recently come to the fore: they generally require
      less memory than their classical counterparts. Here, we examine this quantum
      advantage for strongly coupled spin systems-in particular, the Dyson one
      dimensional Ising spin chain with variable interaction length. We find that the
      advantage scales with both interaction range and temperature, growing without
      bound as interaction range increases. In particular, simulating Dyson's original
      spin chain with the most memory-efficient classical algorithm known requires
      infinite memory, while a quantum simulator requires only finite memory. Thus,
      quantum systems can very efficiently simulate strongly coupled one-dimensional
      classical spin systems.

PMID- 28751747
TI  - Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium
      falciparum in culture and P. berghei infection in mouse model.
AB  - A series of phthalimide analogues, novelized with high-valued bioactive scaffolds
      was synthesized by means of click-chemistry under non-conventional microwave
      heating and evaluated as noteworthy growth inhibitors of Plasmodium falciparum
      (3D7 and W2) in culture. Analogues 6a, 6h and 6 u showed highest activity to
      inhibit the growth of the parasite with IC50 values in submicromolar range.
      Structure-activity correlation indicated the necessity of unsubstituted triazoles
      and leucine linker to obtain maximal growth inhibition of the parasite. Notably,
      phthalimide 6a and 6u selectively inhibited the ring-stage growth and parasite
      maturation. On other hand, phthalimide 6h displayed selective schizonticidal
      activity. Besides, they displayed synergistic interactions with chloroquine and
      dihydroartemisinin against parasite. Additional in vivo experiments using P.
      berghei infected mice showed that administration of 6h and 6u alone, as well as
      in combination with dihydroartemisinin, substantially reduced the parasite load.
      The high antimalarial activity of 6h and 6u, coupled with low toxicity advocate
      their potential role as novel antimalarial agents, either as standalone or
      combination therapies.

PMID- 28751748
TI  - Establishment of patient derived xenografts as functional testing of lung cancer
      aggressiveness.
AB  - Despite many years of research efforts, lung cancer still remains the leading
      cause of cancer deaths worldwide. Objective of this study was to set up a
      platform of non-small cell lung cancer patient derived xenografts (PDXs)
      faithfully representing primary tumour characteristics and offering a unique tool
      for studying effectiveness of therapies at a preclinical level. We established 38
      PDXs with a successful take rate of 39.2%. All models closely mirrored parental
      tumour characteristics although a selective pressure for solid patterns, vimentin
      expression and EMT was observed in several models. An increased grafting rate for
      tumours derived from patients with worse outcome (p = 0.006), higher stage (p =
      0.038) and higher CD133+/CXCR4+/EpCAM- stem cell content (p = 0.019) was observed
      whereas a trend towards an association with SUVmax higher than 8 (p = 0.084) was
      detected. Kaplan Meier analyses showed a significantly worse (p = 0.0008) overall
      survival at 5 years in patients with grafted vs not grafted PDXs also after
      adjusting for tumour stage. Moreover, for 63.2% models, grafting was reached
      before clinical recurrence occurred. Our findings strengthen the relevance of
      PDXs as useful preclinical models closely reflecting parental patients tumours
      and highlight PDXs establishment as a functional testing of lung cancer
      aggressiveness and personalized therapies.

PMID- 28751749
TI  - Soil natural capital in europe; a framework for state and change assessment.
AB  - Soils underpin our existence through food production and represent the largest
      terrestrial carbon store. Understanding soil state-and-change in response to
      climate and land use change is a major challenge. Our aim is to bridge the
      science-policy interface by developing a natural capital accounting structure for
      soil, for example, attempting a mass balance between soil erosion and production,
      which indicates that barren land, and woody crop areas are most vulnerable to
      potential soil loss. We test out our approach using earth observation, modelling
      and ground based sample data from the European Union's Land Use/Cover Area frame
      statistical Survey (LUCAS) soil monitoring program. Using land cover change data
      for 2000-2012 we are able to identify land covers susceptible to change, and the
      soil resources most at risk. Tree covered soils are associated with the highest
      carbon stocks, and are on the increase, while areas of arable crops are
      declining, but artificial surfaces are increasing. The framework developed offers
      a substantial step forward, demonstrating the development of biophysical soil
      accounts that can be used in wider socio-economic and policy assessment;
      initiating the development of an integrated soil monitoring approach called for
      by the United Nations Intergovernmental Technical Panel on Soils.

PMID- 28751750
TI  - N-glycan mediated adhesion strengthening during pathogen-receptor binding
      revealed by cell-cell force spectroscopy.
AB  - Glycan-protein lateral interactions have gained increased attention as important
      modulators of receptor function, by regulating surface residence time and
      endocytosis of membrane glycoproteins. The pathogen-recognition receptor DC-SIGN
      is highly expressed at the membrane of antigen-presenting dendritic cells, where
      it is organized in nanoclusters and binds to different viruses, bacteria and
      fungi. We recently demonstrated that DC-SIGN N-glycans spatially restrict
      receptor diffusion within the plasma membrane, favoring its internalization
      through clathrin-coated pits. Here, we investigated the involvement of the N
      glycans of DC-SIGN expressing cells on pathogen binding strengthening when
      interacting with Candida fungal cells by using atomic force microscope (AFM)
      assisted single cell-pathogen adhesion measurements. The use of DC-SIGN mutants
      lacking the N-glycans as well as blocking glycan-mediated lateral interactions
      strongly impaired cell stiffening during pathogen binding. Our findings
      demonstrate for the first time the direct involvement of the cell membrane
      glycans in strengthening cell-pathogen interactions. This study, therefore, puts
      forward a possible role for the glycocalyx as extracellular cytoskeleton
      contributing, possibly in connection with the intracellular actin cytoskeleton,
      to optimize strengthening of cell-pathogen interactions in the presence of
      mechanical forces.

PMID- 28751751
TI  - Understanding the cation ordering transition in high-voltage spinel
      LiNi0.5Mn1.5O4 by doping Li instead of Ni.
AB  - We determined how Li doping affects the Ni/Mn ordering in high-voltage spinel
      LiNi0.5Mn1.5O4(LNMO) by using neutron diffraction, TEM image, electrochemical
      measurements, and NMR data. The doped Li occupies empty octahedral interstitials
      (16c site) before the ordering transition, and can move to normal octahedral
      sites (16d (4b) site) after the transition. This movement strongly affects the
      Ni/Mn ordering transition because Li at 16c sites blocks the ordering transition
      pathway and Li at 16d (4b) sites affects electrostatic interactions with
      transition metals. As a result, Li doping increases in the Ni/Mn disordering
      without the effect of Mn3+ ions even though the Li-doped LNMO undergoes order
      disorder transition at 700  degrees C. Li doping can control the amount of Ni/Mn
      disordering in the spinel without the negative effect of Mn3+ ions on the
      electrochemical property.

PMID- 28751752
TI  - Tannic acid as a plant-derived polyphenol exerts vasoprotection via enhancing
      KLF2 expression in endothelial cells.
AB  - The transcription factor Kruppel-like factor 2 (KLF2) is a critical anti
      inflammatory and anti-atherogenic molecule in vascular endothelium. Enhancing
      KLF2 expression and activity improves endothelial function and prevents
      atherosclerosis. However, the pharmacological and molecular regulators for KLF2
      are scarce. Using high-throughput luciferase reporter assay to screen for KLF2
      activators, we have identified tannic acid (TA), a polyphenolic compound, as a
      potent KLF2 activator that attenuates endothelial inflammation. Mechanistic
      studies suggested that TA induced KLF2 expression in part through the ERK5/MEF2
      pathway. Functionally, TA markedly decreased monocyte adhesion to ECs by reducing
      expression of adhesion molecule VCAM1. Using lung ECs isolated from Klf2 +/+ and
      Klf2 +/- mice, we showed that the anti-inflammatory effect of TA is dependent on
      KLF2. Collectively, our results demonstrate that TA is a potent KLF2 activator
      and TA attenuated endothelial inflammation through upregulation of KLF2. Our
      findings provide a novel mechanism for the well-established beneficial
      cardiovascular effects of TA and suggest that KLF2 could be a novel therapeutic
      target for atherosclerotic vascular disease.

PMID- 28751753
TI  - Easily Regenerated Readily Deployable Absorbent for Heavy Metal Removal from
      Contaminated Water.
AB  - Although clean and abundant water is the keystone of thriving communities,
      increasing demand and volatile climate patterns are depleting rivers and
      aquifers. Moreover, the quality of such water sources is threatened by noxious
      contaminants, of which heavy metals represents an area of growing concern.
      Recently, graphene oxide (GO) has been suggested as an adsorbent; however, a
      support is desirable to ensure a high surface area and an immobile phase. Herein,
      we described the preparation and characterization of a supported-epoxidized
      carbon nanotube (SENT) via the growth of multi walled carbon nanotubes (MWNTs)
      onto a quartz substrate. Subsequent epoxidation provides sufficient functionality
      to enable adsorbent of heavy metals (Cd2+, Co2+, Cu2+, Hg2+, Ni2+, and Pb2+) from
      aqueous solution with initial concentrations (60-6000 ppm) chosen to simulate
      high industrial wastewater contamination. The SENT adsorption efficiency is
      >99.4% for all metals and the saturation concentration is significantly greater
      than observed for either GO or acid treated MWNTs. The SENT adsorbent may be
      readily regenerated under mild conditions using a globally available household
      chemical, vinegar. 1 g of SENT has the potential to treat 83,000 L of
      contaminated water down to WHO limits which would be sufficient for 11,000
      people.

PMID- 28751754
TI  - A First Phylogeny of the Genus Dimocarpus and Suggestions for Revision of Some
      Taxa Based on Molecular and Morphological Evidence.
AB  - Dimocarpus longan, commonly known as the longan, belongs to the family
      Sapindaceae, and is one of the most economically important fruits commonly
      cultivated in several regions in Asia. There are various cultivars of longan
      throughout the Thai-Malay peninsula region, but until now no phylogenetic
      analysis has been undertaken to determine the genetic relatedness of these
      cultivars. To address this issue, 6 loci, namely ITS2, matK, rbcL, trnH-psbA,
      trnL-I and trnL-trnF were amplified and sequenced from 40 individuals consisting
      of 26 longan cultivars 2 types of lychee and 8 herbarium samples. The sequencing
      results were used to construct a phylogenetic tree using the neighbor-joining
      (NJ), maximum likelihood (ML) and Bayesian inference (BI) criteria. The tree
      showed cryptic groups of D. longan from the Thailand-Malaysia region (Dimocarpus
      longan spp.). This is the first report of the genetic relationship of Dimocarpus
      based on multi-locus molecular markers and morphological characteristics.
      Multiple sequence alignments, phylogenetic trees and species delimitation support
      that Dimocarpus longan spp. longan var. obtusus and Dimocarpus longan spp.
      malesianus var. malesianus should be placed into a higher order and are two
      additional species in the genus Dimocarpus. Therefore these two species require
      nomenclatural changes as Dimocarpus malesianus and Dimocarpus obtusus,
      respectively.

PMID- 28751755
TI  - TCTP as a therapeutic target in melanoma treatment.
AB  - BACKGROUND: Translationally controlled tumour protein (TCTP) is an antiapoptotic
      protein highly conserved through phylogeny. Translationally controlled tumour
      protein overexpression was detected in several tumour types. Silencing TCTP was
      shown to induce tumour reversion. There is a reciprocal repression between TCTP
      and P53. Sertraline interacts with TCTP and decreases its cellular levels.
      METHODS: We evaluate the role of TCTP in melanoma using sertraline and siRNA.
      Cell viability, migration, and clonogenicity were assessed in human and murine
      melanoma cells in vitro. Sertraline was evaluated in a murine melanoma model and
      was compared with dacarbazine, a major chemotherapeutic agent used in melanoma
      treatment. RESULTS: Inhibition of TCTP levels decreases melanoma cell viability,
      migration, clonogenicity, and in vivo tumour growth. Human melanoma cells treated
      with sertraline show diminished migration properties and capacity to form
      colonies. Sertraline was effective in inhibiting tumour growth in a murine
      melanoma model; its effect was stronger when compared with dacarbazine.
      CONCLUSIONS: Altogether, these results indicate that sertraline could be
      effective against melanoma and TCTP can be a target for melanoma therapy.

PMID- 28751756
TI  - Knowledge or noise? Making sense of General Practitioners' and Consultant use of
      2-week-wait referrals for suspected cancer.
AB  - BACKGROUND: Early diagnosis and treatment of cancer is the goal of the 2-week
      wait referral pathway (2WW). Variation exists between General Practice use of 2WW
      and rates of consultant reprioritisation of GP referral from routine to 2WW
      (Consultant Upgrade). We investigated variation in General Practice and
      Consultant Upgrade 2WW referral activity. METHODS: Data from 185 000 referrals
      and 29 000 cancers recorded between 2011 and 2013 from the Northern Ireland
      Cancer Waiting Time database (CaPPS) were analysed to ascertain standardised
      referral rate ratios, detection rate (DR) (=sensitivity) and conversion rate (CR)
      (=positive predictive value) for Practice 2WW referrals and Consultant Upgrade
      2WW. Metrics were compared using Spearman's rank correlation co-efficients.
      RESULTS: There was consistency in Practice and Consultant Upgrade 2WW referral
      rates over time, though not for annual DR (Spearman's rho<0.37) or CR (Spearman's
      rho<0.26). Practice 2WW referral rates correlated negatively with CR and
      positively with DR while correlations between DR and CR were restricted to single
      year comparisons in Practice 2WW. In Consultant Upgrade, 2WW CR and DR were
      strongly correlated but only when the same cancers were included in both rates.
      CONCLUSIONS: Results suggest 'random case mix' explains previously reported
      associations between CR and DR with more 'hard to detect' cancers in some
      Practices than in others in a given year corresponding to lower DR and CR. Use of
      Practice and Consultant Upgrade 2WW referral metrics to gauge General Practice
      performance may be misleading.

PMID- 28751757
TI  - Expression of L1CAM in curettage or high L1CAM level in preoperative blood
      samples predicts lymph node metastases and poor outcome in endometrial cancer
      patients.
AB  - BACKGROUND: Several studies have identified L1 cell adhesion molecule (L1CAM) as
      a strong prognostic marker in endometrial cancer. To further underline the
      clinical usefulness of this biomarker, we investigated L1CAM as a predictive
      marker for lymph node metastases and its prognostic impact in curettage specimens
      and preoperative plasma samples. In addition, we aimed to validate the prognostic
      value of L1CAM in hysterectomy specimen. METHODS: Immunohistochemical staining of
      L1CAM was performed for 795 hysterectomy and 1134 curettage specimen from
      endometrial cancer patients. The L1CAM level in preoperative blood samples from
      372 patients was determined using ELISA. RESULTS: Expression of L1CAM in
      curettage specimen was significantly correlated to L1CAM level in corresponding
      hysterectomy specimen (P<0.001). Both in curettage and preoperative plasma
      samples L1CAM upregulation was significantly associated with features of
      aggressive disease and poor outcome (P<0.001). The L1CAM was an independent
      predictor of lymph node metastases, after correction for curettage histology,
      both in curettage specimen (P=0.002) and plasma samples (P=0.048). In the
      hysterectomy samples L1CAM was significantly associated with poor outcome
      (P<0.001). CONCLUSIONS: We demonstrate that preoperative evaluation of L1CAM
      levels, both in curettage or plasma samples, predicts lymph node metastases and
      adds valuable information on patient prognosis.

PMID- 28751758
TI  - Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Identifying informative prognostic biomarkers for oral tongue
      squamous cell carcinoma (OTSCC) is of great importance in order to better predict
      tumour behaviour and to guide treatment planning. Here, we summarise existing
      evidence regarding immunohistochemical prognostic biomarkers for OTSCC. METHODS:
      A systematic search of the literature was performed using the databases of
      Scopus, Ovid Medline, Web of Science and Cochrane Library. All studies which had
      investigated the prognostic significance of immunohistochemical biomarkers in
      OTSCC during the period from 1985 to 2015 were retrieved. For the five most often
      evaluated biomarkers a random-effects meta-analysis on overall survival was
      performed, including those studies that provided the necessary statistical
      results. RESULTS: A total of 174 studies conducted during the last three decades
      were found, and in these 184 biomarkers were evaluated for the prognostication of
      OTSCC. The five biomarkers most frequently assessed were p53, Ki-67, p16, VEGFs
      and cyclin D1. In the meta-analyses, the most promising results of the prognostic
      power for OTSCC were obtained for cyclin D1. For studies of VEGF A and C the
      results were equivocal, but the pooled analysis of VEGF A separately showed it to
      be a useful prognosticator for OTSCC. There was no sufficient evidence to support
      p53, Ki-67 and p16 as prognostic biomarkers for OTSCC. Limitations in the quality
      of the published studies (e.g., small cohorts, lack of compliance with REMARK
      guidelines) are widespread. CONCLUSIONS: Numerous biomarkers have been presented
      as useful prognosticators for OTSCC, but the quality of the conduct and reporting
      of original studies is overall unsatisfactory which does not allow reliable
      conclusions. The value of two biomarkers (VEGF-A and cyclin D1) should be
      validated in a multicentre study setting following REMARK guidelines.

PMID- 28751759
TI  - A comparative study of germline BRCA1 and BRCA2 mutation screening methods in use
      in 20 European clinical diagnostic laboratories.
AB  - BACKGROUND: Thousands of clinically relevant variations in BRCA1 and BRCA2 have
      been discovered and this poses a significant challenge with respect to the
      accurate detection, analysis turn-around time, characterisation and
      interpretation of these sequence variants. METHODS: We evaluated the performance
      of different BRCA1/2 gene testing practices in routine diagnostic use in 20
      European laboratories, with a focus on next-generation sequencing-based
      strategies as this is the technical approach implemented by or under adoption by
      most European clinical laboratories. Participant laboratories, selected on
      expertise and diagnostic service quality, tested 10 identical DNA samples
      containing a range of challenging pathogenic variants. RESULTS: A small number of
      errors in the detection of pathogenic and significant variants were identified
      (2.6% diagnostic error rate). There was a high degree of concordance (>97%)
      across all laboratories for all variants detected. No systematic technical flaw
      was identified in the strategies employed across the participating laboratories.
      CONCLUSIONS: The discrepancies identified are most likely due to human error or
      the way the methodology has been implemented locally, for example, next
      generation sequencing bioinformatics pipelines, rather than technical limitations
      of the methods. The choice of BRCA1/2 testing method will therefore depend on
      multiple factors including required throughput and turn-around times, access to
      equipment, expertise and budget.

PMID- 28751760
TI  - IL28B rs12979860 genotype as a predictor marker of progression to BKVirus
      Associated nephropathy, after kidney transplantation.
AB  - BK virus (BKV) associated nephropathy (BKVAN) is still an important cause of
      allograft dysfunction after kidney transplantation (KT). Recent data have shown
      that the new interferon (IFN)-lambda family has been ascribed antiviral
      properties similar to IFNalpha, and that the response to IFNlambda in kidney is
      restricted to epithelial cells, suggesting that the IFNlambda system evolves as
      specific protection of the epithelia. We aimed to test the hypothesis of
      correlation between a single nucleotide polymorphism (C/T dimorphism rs12979860)
      in the genomic region of IL28B and BKVAN, in patients after KT. Fifty kidney
      transplanted patients were included as follow: Group 1 (BKV+/BKVAN+): 11 patients
      with active BKV- replication and biopsy-proven BKVAN; Group 2 (BKV+/BKVAN-): 22
      patients with active BKV- replication but without evidence of BKVAN; Group 3 (BKV
      /BKVAN-): 17 patients without evidence of BKV- replication (control group). Here
      we show that the C/C genotype was statistically higher in group 2 than in group 1
      and BKVAN was detected significantly more frequently in patients with C/T and T/T
      genotypes than in patients with C/C genotype. We therefore propose IL28B
      polymorphism (rs12979860), as a predictor-marker to differentiate between
      patients with self-limited, even if persistent, BKV- reactivation and patients
      with a high risk of progression towards BKVAN, and to modulate the clinical
      management of these patients accordingly.

PMID- 28751761
TI  - Controlling bi-anisotropy in infrared metamaterials using three-dimensional split
      ring-resonators for purely magnetic resonance.
AB  - We propose and demonstrate the strategy to control bi-anisotropic response in
      three-dimensional split-ring-resonators (3D-SRRs) array for purely magnetic
      resonance in the mid-infrared region. By using a metal-stress-driven self-folding
      method, inversion symmetry along a propagation axis of 3D-SRRs was controlled.
      The inversion symmetry of 3D-SRRs realized non-bi-anisotropic response of a
      magnetic resonant mode at around 10 MUm in wavelength resulting in purely
      magnetic resonance with high transmission of 70%. Highly transparent purely
      magnetic artificial elements demonstrated in this study will be a key component
      for functional applications using artificial magnetism at the optical
      frequencies.

PMID- 28751762
TI  - Gastric and intestinal proteases resistance of chicken acidic chitinase nominates
      chitin-containing organisms for alternative whole edible diets for poultry.
AB  - Chitin, a polymer of N-acetyl-D-glucosamine (GlcNAc), functions as a major
      structural component in crustaceans, insects and fungi and is the second most
      abundant polysaccharide in the nature. Although these chitin-containing organisms
      have been suggested as novel animal feed resources, chitin has long been
      considered as indigestible fibers in the animal body. Recently, we reported that
      acidic chitinase (Chia) is a protease-resistant major glycosidase in mouse
      gastrointestinal tract (GIT) and that it digests chitin in the mouse stomach.
      However, the physiological role of Chia in other animals including poultry
      remains unknown. Here, we report that Chia can function as a digestive enzyme
      that breaks down chitin-containing organisms in chicken GIT. Chia mRNA is
      predominantly expressed in the glandular stomach tissue in normal chicken. We
      also show that chicken Chia has a robust chitinolytic activity at pH 2.0 and is
      highly resistant to proteolysis by pepsin and trypsin/chymotrypsin under
      conditions mimicking GIT. Chia degraded shells of mealworm larvae in the presence
      of digestive proteases and produced (GlcNAc)2. Thus, functional similarity of
      chicken Chia with the mouse enzyme suggests that chitin-containing organisms can
      be used for alternative poultry diets not only as whole edible resources but also
      as enhancers of their nutritional value.

PMID- 28751763
TI  - Modifiable risk factors in the first 1000 days for subsequent risk of childhood
      overweight in an Asian cohort: significance of parental overweight status.
AB  - BACKGROUND/OBJECTIVE: Many studies have identified early-life risk factors for
      subsequent childhood overweight/obesity, but few have evaluated how they combine
      to influence risk of childhood overweight/obesity. We examined associations,
      individually and in combination, of potentially modifiable risk factors in the
      first 1000 days after conception with childhood adiposity and risk of
      overweight/obesity in an Asian cohort. METHODS: Six risk factors were examined:
      maternal pre-pregnancy overweight/obesity (body mass index (BMI) ?25 kg m-2),
      paternal overweight/obesity at 24 months post delivery, maternal excessive
      gestational weight gain, raised maternal fasting glucose during pregnancy (?5.1
      mmol l-1), breastfeeding duration <4 months and early introduction of solid foods
      (<4 months). Associations between number of risk factors and adiposity measures
      (BMI, waist-to-height ratio (WHtR), sum of skinfolds (SSFs), fat mass index (FMI)
      and overweight/obesity) at 48 months were assessed using multivariable regression
      models. RESULTS: Of 858 children followed up at 48 months, 172 (19%) had none,
      274 (32%) had 1, 244 (29%) had 2, 126 (15%) had 3 and 42 (5%) had ?4 risk
      factors. Adjusting for confounders, significant graded positive associations were
      observed between number of risk factors and adiposity outcomes at 48 months.
      Compared with children with no risk factors, those with four or more risk factors
      had s.d. unit increases of 0.78 (95% confidence interval 0.41-1.15) for BMI, 0.79
      (0.41-1.16) for WHtR, 0.46 (0.06-0.83) for SSF and 0.67 (0.07-1.27) for FMI. The
      adjusted relative risk of overweight/obesity in children with four or more risk
      factors was 11.1(2.5-49.1) compared with children with no risk factors. Children
      exposed to maternal pre-pregnancy (11.8(9.8-13.8)%) or paternal overweight status
      (10.6(9.6-11.6)%) had the largest individual predicted probability of child
      overweight/obesity. CONCLUSIONS: Early-life risk factors added cumulatively to
      increase childhood adiposity and risk of overweight/obesity. Early-life and
      preconception intervention programmes may be more effective in preventing
      overweight/obesity if they concurrently address these multiple modifiable risk
      factors.

PMID- 28751764
TI  - A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma
      induces selective lysis in vitro and in vivo.
AB  - This corrects the article DOI: 10.1038/leu.2016.388.

PMID- 28751765
TI  - A TLR7 agonist enhances the antitumor efficacy of obinutuzumab in murine lymphoma
      models via NK cells and CD4 T cells.
AB  - This corrects the article DOI: 10.1038/leu.2016.352.

PMID- 28751766
TI  - Foragers of sympatric Asian honey bee species intercept competitor signals by
      avoiding benzyl acetate from Apis cerana alarm pheromone.
AB  - While foraging, animals can form inter- and intraspecific social signalling
      networks to avoid similar predators. We report here that foragers of different
      native Asian honey bee species can detect and use a specialized alarm pheromone
      component, benzyl acetate (BA), to avoid danger. We analysed the volatile alarm
      pheromone produced by attacked workers of the most abundant native Asian honey
      bee, Apis cerana and tested the responses of other bee species to these alarm
      signals. As compared to nest guards, A. cerana foragers produced 3.38 fold higher
      levels of BA. In foragers, BA and (E)-dec-2-en-1-yl acetate (DA) generated the
      strongest antennal electrophysiological responses. BA was also the only compound
      that alerted flying foragers and inhibited A. cerana foraging. BA thereby
      decreased A. cerana foraging for risky sites. Interestingly, although BA occurs
      only in trace amounts and is nearly absent in sympatric honeybee species
      (respectively only 0.07% and 0.44% as much in A. dorsata and A. florea), these
      floral generalists detected and avoided BA as strongly as they did to their own
      alarm pheromone on natural inflorescences. These results demonstrate that
      competing pollinators can take advantage of alarm signal information provided by
      other species.

PMID- 28751767
TI  - Ultrafast intersystem crossings in Fe-Co Prussian blue analogues.
AB  - Ultrafast spincrossover is studied in Fe-Co Prussian blue analogues using a
      dissipative quantum-mechanical model of a cobalt ion coupled to a breathing mode.
      All electronic interactions are treated on an equal footing. It is theoretically
      demonstrated that the divalent cobalt ion reaches 90% of the [Formula: see text]
      value within 20 fs after photoexciting a low-spin Co3+ ion by an iron-to-cobalt
      charge transfer. The doublet-to-quartet spin crossover is significantly faster
      than the oscillation period of the breathing mode. The system relaxes to the
      lowest manifold of divalent cobalt (4 T 1) in 150-200 fs. Strong oscillations in
      spin-orbit coupling and the involvement of higher-lying quartets are found.

PMID- 28751768
TI  - Cytogenetically cryptic ZMYM2-FLT3 and DIAPH1-PDGFRB gene fusions in myeloid
      neoplasms with eosinophilia.

PMID- 28751769
TI  - Phase I/II study of the deacetylase inhibitor panobinostat after allogeneic stem
      cell transplantation in patients with high-risk MDS or AML (PANOBEST trial).

PMID- 28751770
TI  - Enhancing venetoclax activity in acute myeloid leukemia by co-targeting MCL1.
AB  - Targeted therapies are frequently combined with standard cytotoxic drugs to
      enhance clinical response. Targeting the B-cell lymphoma 2 (BCL-2) family of
      proteins is an attractive option to combat chemoresistance in leukemia.
      Preclinical and clinical studies indicate modest single-agent activity with
      selective BCL-2 inhibitors (for example, venetoclax). We show that venetoclax
      synergizes with cytarabine and idarubicin to increase antileukemic efficacy in a
      TP53-dependent manner. Although TP53 deficiency impaired sensitivity to combined
      venetoclax and chemotherapy, higher-dose idarubicin was able to suppress MCL1 and
      induce cell death independently of TP53. Consistent with an MCL1-specific effect,
      cell death from high-dose idarubicin was dependent on pro-apoptotic Bak.
      Combining higher-dose idarubicin with venetoclax was able to partially overcome
      resistance in Bak-deficient cells. Using inducible vectors and venetoclax to
      differentially target anti-apoptotic BCL-2 family members, BCL-2 and MCL1 emerged
      as critical and complementary proteins regulating cell survival in acute myeloid
      leukemia. Dual targeting of BCL-2 and MCL1, but not either alone, prolonged
      survival of leukemia-bearing mice. In conclusion, our findings support the
      further investigation of venetoclax in combination with standard chemotherapy,
      including intensified doses of idarubicin. Venetoclax should also be investigated
      in combination with direct inhibitors of MCL1 as a chemotherapy-free approach in
      the future.

PMID- 28751771
TI  - Number of RUNX1 mutations, wild-type allele loss and additional mutations impact
      on prognosis in adult RUNX1-mutated AML.
AB  - RUNX1-mutated acute myeloid leukemia (AML) show a distinct pattern of genetic
      abnormalities and an adverse prognosis. We analyzed the impact of multiple RUNX1
      mutations and RUNX1 wild-type (WT) loss in 467 AML with RUNX1 mutations (mut):
      (1) RUNX1 WT loss (n=53), (2) >1 RUNX1mut (n=94) and (3) 1 RUNX1mut (n=323). In 1
      RUNX1mut, +8 was most frequent, whereas in WT loss +13 was the most abundant
      trisomy (+8: 66% vs 31%, P=0.022; +13: 15% vs 62%, P<0.001). Analyses of 28 genes
      in 163 selected cases revealed SRSF2 (39%), ASXL1 (36%), DNMT3A (19%), IDH2 (17%)
      and SF3B1 (17%) as most frequently mutated genes. RUNX1 WT loss showed a higher
      frequency of ASXL1mut compared with the other cases (50% vs 29%, P=0.009). Median
      overall survival (OS) in the total cohort was 14 months. WT loss (OS: 5 months)
      and >1 RUNX1mut (14 months) showed an adverse impact on prognosis compared with 1
      RUNX1mut (22 months; P=0.002 and 0.048, respectively). Mutations in ASXL1 and ?2
      additional mutations correlated with shorter OS (10 vs 18 months, P=0.028; 12 vs
      20 months, P=0.017). Thus, the number of RUNX1mut, RUNX1 WT loss and the number
      and type of additional mutations is biologically and clinically relevant.

PMID- 28751772
TI  - Inhibition of reactive oxygen species limits expansion of chronic lymphocytic
      leukemia cells.

PMID- 28751773
TI  - Influence of IDH on FLT3-ITD status in newly diagnosed AML.

PMID- 28751774
TI  - The assembly competence domain is essential for inv(16)-associated acute myeloid
      leukemia.

PMID- 28751775
TI  - Graphene transistors for interfacing with cells: towards a deeper understanding
      of liquid gating and sensitivity.
AB  - This work is focused on the fabrication and analysis of graphene-based, solution
      gated field effect transistor arrays (GFETs) on a large scale for bioelectronic
      measurements. The GFETs fabricated on different substrates, with a variety of
      gate geometries (width/length) of the graphene channel, reveal a linear relation
      between the transconductance and the width/length ratio. The area normalised
      electrolyte-gated transconductance is in the range of 1-2 mS.V-1.? and does not
      strongly depend on the substrate. Influence of the ionic strength on the
      transistor performance is also investigated. Double contacts are found to
      decrease the effective resistance and the transfer length, but do not improve the
      transconductance. An electrochemical annealing/cleaning effect is investigated
      and proposed to originate from the out-of-plane gate leakage current. The devices
      are used as a proof-of-concept for bioelectronic sensors, recording external
      potentials from both: ex vivo heart tissue and in vitro cardiomyocyte-like HL-1
      cells. The recordings show distinguishable action potentials with a signal to
      noise ratio over 14 from ex vivo tissue and over 6 from the cardiac-like cell
      line in vitro. Furthermore, in vitro neuronal signals are recorded by the
      graphene transistors with distinguishable bursting for the first time.

PMID- 28751776
TI  - Hobit expression by a subset of human liver-resident CD56bright Natural Killer
      cells.
AB  - Immune responses show a high degree of tissue specificity shaped by factors
      influencing tissue egress and retention of immune cells. The transcription factor
      Hobit was recently shown to regulate tissue-residency in mice. Whether Hobit acts
      in a similar capacity in humans remains unknown. Our aim was to assess the
      expression and contribution of Hobit to tissue-residency of Natural Killer (NK)
      cells in the human liver. The human liver was enriched for CD56bright NK cells
      showing increased expression levels of the transcription factor Hobit. Hobitpos
      CD56bright NK cells in the liver exhibited high levels of CD49a, CXCR6 and CD69.
      Hobitpos CD56bright NK cells in the liver furthermore expressed a unique set of
      transcription factors with higher frequencies and levels of T-bet and Blimp-1
      when compared to Hobitneg CD56bright NK cells. Taken together, we show that the
      transcription factor Hobit identifies a subset of NK cells in human livers that
      express a distinct set of adhesion molecules and chemokine receptors consistent
      with tissue residency. These data suggest that Hobit is involved in regulating
      tissue-residency of human intrahepatic CD56bright NK cells in a subset of NK
      cells in inflamed livers.

PMID- 28751777
TI  - Action-based Modeling of Complex Networks.
AB  - Complex networks can model a wide range of complex systems in nature and society,
      and many algorithms (network generators) capable of synthesizing networks with
      few and very specific structural characteristics (degree distribution, average
      path length, etc.) have been developed. However, there remains a significant lack
      of generators capable of synthesizing networks with strong resemblance to those
      observed in the real-world, which can subsequently be used as a null model, or to
      perform tasks such as extrapolation, compression and control. In this paper, a
      robust new approach we term Action-based Modeling is presented that creates a
      compact probabilistic model of a given target network, which can then be used to
      synthesize networks of arbitrary size. Statistical comparison to existing network
      generators is performed and results show that the performance of our approach is
      comparable to the current state-of-the-art methods on a variety of network
      measures, while also yielding easily interpretable generators. Additionally, the
      action-based approach described herein allows the user to consider an arbitrarily
      large set of structural characteristics during the generator design process.

PMID- 28751778
TI  - A decreasing glacier mass balance gradient from the edge of the Upper Tarim Basin
      to the Karakoram during 2000-2014.
AB  - In contrast to the glacier mass losses observed at other locations around the
      world, some glaciers in the High Mountains of Asia appear to have gained mass in
      recent decades. However, changes in digital elevation models indicate that
      glaciers in Karakoram and Pamir have gained mass, while recent laser altimetry
      data indicate mass gain centred on West Kunlun. Here, we obtain results that are
      essentially consistent with those from altimetry, but with two-dimensional
      observations and higher resolution. We produced elevation models using radar
      interferometry applied to bistatic data gathered between 2011 and 2014 and
      compared them to a model produced from bistatic data collected in 2000. The
      glaciers in West Kunlun, Eastern Pamir and the northern part of Karakoram
      experienced a clear mass gain of 0.043 +/- 0.078~0.363 +/- 0.065 m w.e. yr-1. The
      Karakoram showed a near-stable mass balance in its western part (-0.020 +/- 0.064
      m w.e. yr-1), while the Eastern Karakoram showed mass loss (-0.101 +/- 0.058 m
      w.e. yr-1). Significant positive glacier mass balances are noted along the edge
      of the Upper Tarim Basin and indicate a decreasing gradient from northeast to
      southwest.

PMID- 28751779
TI  - MiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the
      Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi
      Apparatus.
AB  - Because several studies have shown that exogenous miR-199a has antiviral effects
      against various viruses, including herpesviruses, we examined how miR-199a exerts
      its antiviral effects using epithelial tumour cell lines infected with herpes
      simplex virus-1 (HSV-1). We found that both miR-199a-5p and -3p impair the
      secondary envelopment of HSV-1 by suppressing their common target, ARHGAP21, a
      Golgi-localized GTPase-activating protein for Cdc42. We further found that the
      trans-cisternae of the Golgi apparatus are a potential membrane compartment for
      secondary envelopment. Exogenous expression of either pre-miR-199a or sh-ARHGAP21
      exhibited shared phenotypes i.e. alteration of Golgi function in uninfected
      cells, inhibition of HSV-1 secondary envelopment, and reduction of trans-Golgi
      proteins upon HSV-1 infection. A constitutively active form of Cdc42 also
      inhibited HSV-1 secondary envelopment. Endogenous levels of miR-199a in
      epithelial tumour cell lines were negatively correlated with the efficiency of
      HSV-1 secondary envelopment within these cells. These results suggest that miR
      199a is a crucial regulator of Cdc42 activity on Golgi membranes, which is
      important for the maintenance of Golgi function and for the secondary envelopment
      of HSV-1 upon its infection.

PMID- 28751780
TI  - TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever
      virus replication.
AB  - Classical swine fever virus (CSFV) non-structural protein 3 (NS3) is a
      multifunctional non-structural protein that plays a major role in viral
      replication. However, how exactly NS3 exerts these functions remains unknown.
      Here, we identified tumour necrosis factor receptor-associated factor 6 (TRAF6)
      as a novel NS3-interacting protein via yeast two-hybrid analysis, co
      immunoprecipitation, and glutathione S-transferase pull-down assays. Furthermore,
      we observed that TRAF6 overexpression significantly inhibited CSFV replication,
      and TRAF6 knockdown promoted CSFV replication in porcine alveolar macrophages.
      Additionally, TRAF6 was degraded during CSFV infection or NS3 expression
      exclusively, indicating that CSFV and TRAF6 were mutually antagonistic and that
      TRAF6 degradation might contribute to persistent CSFV replication. Moreover,
      nuclear factor-kappa B (NF-kappaB) activity and interferon (IFN)-beta and
      interleukin (IL)-6 expression were increased in TRAF6-overexpressing cells,
      whereas TRAF6-knockdown cells exhibited decreased NF-kappaB activity and IFN-beta
      and IL-6 levels. Notably, TRAF6 overexpression did not reduce CSFV replication
      following inhibition of NF-kappaB activation by p65 knockdown. Our findings
      revealed that TRAF6 inhibits CSFV replication via activation of NF-kappaB
      signalling pathways along with increases in the expression of its targets IFN
      beta and IL-6. This work addresses a novel aspect concerning the regulation of
      innate antiviral immune response during CSFV infection.

PMID- 28751781
TI  - Lower mean platelet volume predicts poor prognosis in renal cell carcinoma.
AB  - Altered mean platelet volume (MPV) is found in several malignancies. Remarkably,
      there is little consensus on using the value of MPV in the prognostic evaluations
      of renal cell carcinoma (RCC). The aim of this study is to examine the
      feasibility of MPV value as a prognostic indicator of RCC. The retrospective
      study recruited 306 consecutive RCC patients between January 2009 and December
      2009. The relationships between MPV and clinicopathological characteristics were
      analyzed. Kaplan-Meier method and Cox regression were used to evaluate the
      prognostic impact of MPV. Of the 306 RCC patients, low MPV levels were detected
      in 61 (19.9%) patients. Reduced MPV was associated with histology types, T
      classification, UCLA Integrated Scoring System (UISS) category, and Mayo clinic
      stage, size, grade, and necrosis score (SSIGN) category (P < 0.05). Patients with
      decreased MPV had significantly shorter survival time than patients with normal
      MPV (P < 0.001). Cox regression analysis revealed that reduced MPV was an
      independent prognostic factor for overall survival (hazard ratio, 1.758; 95%
      confidence interval [CI], 1.083-2.855, P = 0.023). Moreover, the prognostic
      accuracy of TNM stage, UISS, and SSIGN prognostic models were improved when MPV
      was added. In conclusion, reduced MPV is identified as an independent predictor
      of adverse clinical outcome in RCC.

PMID- 28751782
TI  - Reconstruction of local frequencies for recovering the unwrapped phase in optical
      interferometry.
AB  - In optics, when interferograms or digital holograms are recorded and their phase
      is recovered, it is common to obtain a wrapped phase with some errors, noise and
      artifacts such as singularities due to the non linearities of the demodulation
      process. This paper shows how to reconstruct the frequency field of the wrapped
      phase by using adaptive Gabor filters. Gabor filters are Gaussian quadrature
      filters tuned in at a certain frequency. We adapt these Gabor filters by tuning
      them locally and estimating the frequency using wrapped finite differences of the
      estimated phase. Doing this process iteratively, the frequency estimation is
      refined and smoothed. The unwrapped phase is easily recovered by integrating the
      recovered frequency field using, for example, a simple line raster integration.
      We don't have problems with phase inconsistencies or residues while integrating
      the phase, because these are removed. The obtained unwrapped phase is clean,
      consistent and practically error-free. We show estimation errors with simulated
      data and the performance of the proposed method using real-world recorded
      wavefronts.

PMID- 28751783
TI  - A Facile and Flexible Method for On-Demand Directional Speed Tunability in the
      Miniaturised Lab-on-a-Disc.
AB  - The Miniaturised Lab-on-a-Disc (miniLOAD) platform, which utilises surface
      acoustic waves (SAWs) to drive the rotation of thin millimeter-scale discs on
      which microchannels can be fabricated and hence microfluidic operations can be
      performed, offers the possibility of miniaturising its larger counterpart, the
      Lab-on-a-CD, for true portability in point-of-care applications. A significant
      limitation of the original miniLOAD concept, however, is that it does not allow
      for flexible control over the disc rotation direction and speed without manual
      adjustment of the disc's position, or the use of multiple devices to alter the
      SAW frequency. In this work, we demonstrate the possibility of achieving such
      control with the use of tapered interdigitated transducers to confine a SAW beam
      such that the localised acoustic streaming it generates imparts a force, through
      hydrodynamic shear, at a specific location on the disc. Varying the torque that
      arises as a consequence by altering the input frequency to the transducers then
      allows the rotational velocity and direction of the disc to be controlled with
      ease. We derive a simple predictive model to illustrate the principle by which
      this occurs, which we find agrees well with the experimental measurements.

PMID- 28751784
TI  - Rapid generation of OPC-like cells from human pluripotent stem cells for treating
      spinal cord injury.
AB  - Remyelination via the transplantation of oligodendrocyte precursor cells (OPCs)
      has been considered as a strategy to improve the locomotor deficits caused by
      traumatic spinal cord injury (SCI). To date, enormous efforts have been made to
      derive OPCs from human pluripotent stem cells (hPSCs), and significant progress
      in the transplantation of such cells in SCI animal models has been reported. The
      current methods generally require a long period of time (>2 months) to obtain
      transplantable OPCs, which hampers their clinical utility for patients with SCI.
      Here we demonstrate a rapid and efficient method to differentiate hPSCs into
      neural progenitors that retain the features of OPCs (referred to as OPC-like
      cells). We used cell sorting to select A2B5-positive cells from hPSC-derived
      neural rosettes and cultured the selected cells in the presence of signaling
      cues, including sonic hedgehog, PDGF and insulin-like growth factor-1. This
      method robustly generated neural cells positive for platelet-derived growth
      factor receptor-alpha (PDGFRalpha) and NG2 (~90%) after 4 weeks of
      differentiation. Behavioral tests revealed that the transplantation of the OPC
      like cells into the spinal cords of rats with contusive SCI at the thoracic level
      significantly improved hindlimb locomotor function. Electrophysiological
      assessment revealed enhanced neural conduction through the injury site.
      Histological examination showed increased numbers of axon with myelination at the
      injury site and graft-derived myelin formation with no evidence of tumor
      formation. Our method provides a cell source from hPSCs that has the potential to
      recover motor function following SCI.

PMID- 28751786
TI  - Political motivations for intra-European migration.
AB  - Motivations for migrating within the European Union have mainly been attributed
      to economic, career and lifestyle choices. This article suggests that political
      dissatisfaction is also an important motivator of recent intra-European
      migration. In our analysis of in-depth interviews with Romanian migrants in Spain
      and with Spanish migrants in Norway, we found a common emphasis on the political
      dimensions of their decision to migrate. In the interviews, the economic
      component of migration was often related to bad governance and negative
      perceptions of the state. The similarities of Spanish and Romanian migration
      narratives are especially striking because Spain and Romania represent
      substantially different migratory, political and economic contexts. However,
      migration is more obviously intertwined with conventional acts of political
      protest in the Spanish case. We suggest that differences in democratic contexts
      are pivotal in people's reactions to and framing of their deep dissatisfaction
      with domestic politics, as found in many European countries today.

PMID- 28751785
TI  - CTLA4-CD28 chimera gene modification of T cells enhances the therapeutic efficacy
      of donor lymphocyte infusion for hematological malignancy.
AB  - Donor lymphocyte infusion (DLI) followed by hematopoietic stem cell
      transplantation has served as an effective prevention/treatment modality against
      the relapse of some hematologic tumors, such as chronic myeloid leukemia (CML).
      However, the therapeutic efficacies of DLI for other types of leukemia, including
      acute lymphocytic leukemia (ALL), have been limited thus far. Therefore, we
      examined whether increasing the reactivity of donor T cells by gene modification
      could enhance the therapeutic efficacy of DLI in a murine model of ALL. When a
      CTLA4-CD28 chimera gene (CTC28) in which the intracellular signaling domain of
      CTLA4 was replaced with the CD28 signaling domain was introduced into CD4 and CD8
      T cells in DLI, the graft-versus-tumor (GVT) effect was significantly increased.
      This effect was correlated with an increased expansion of donor CD8 T cells in
      vivo, and the depletion of CD8 T cells abolished this effect. The CD8 T cell
      expansion and the enhanced GVT effect were dependent on the transduction of both
      CD4 and CD8 T cells with CTC28, which emphasizes the role of dual modification in
      this therapeutic effect. The CTC28-transduced T cells that expanded in vivo also
      exhibited enhanced functionality. Although the potentiation of the GVT effect
      mediated by the CTC28 gene modification of T cells was accompanied by an increase
      of graft-versus-host disease (GVHD), the GVHD was not lethal and was mitigated by
      treatment with IL-10 gene-modified third-party mesenchymal stem cells. Thus, the
      combined genetic modification of CD4 and CD8 donor T cells with CTC28 could be a
      promising strategy for enhancing the therapeutic efficacy of DLI.

PMID- 28751787
TI  - Successful Percutaneous Transcatheter Patent Foramen Ovale Closure Through The
      Right Internal Jugular Vein Using Stiff Amplatzer Catheter With A Reshaped Tip.
AB  - Percutaneous transcatheter closure of a patent foramen ovale (PFO) remains
      challenging when femoral venous approach is not available. We describe the
      successful closure of a PFO using the right internal jugular venous approach and
      a catheter delivery system with a reshaped tip in a patient with a PFO, recurrent
      stroke, recurrent gastrointestinal bleeding, bilateral deep venous thrombosis and
      thrombosed bilateral inferior vena cava filter.

PMID- 28751788
TI  - Cigarette Fires Involving Upholstered Furniture in Residences: The Role that
      Smokers, Smoker Behavior, and Fire Standard Compliant Cigarettes Play.
AB  - Residential structure fires pose a significant risk to life and property. A major
      source of these fires is the ignition of upholstered furniture by cigarettes. It
      has long been established that cigarettes and other lighted tobacco products
      could ignite upholstered furniture and were a leading cause of fire deaths in
      residences. In recent years, states have adopted fire standard compliant
      cigarettes ('FSC cigarettes') that are made with a wrapping paper that contains
      regularly spaced bands, which increases the likelihood of self-extinguishment.
      This paper measures the effectiveness of FSC cigarettes on the number of
      residential fires involving upholstered furniture, and the resulting fatalities,
      injuries, and extent of flame spread, while accounting for the under-reporting of
      fire incidents. In total, four models were estimated using fire department data
      from 2002 to 2011. The results provide evidence that FSC cigarettes, on average,
      reduced the number of residential fires by 45 %, reduced fatalities by 23 %, and
      extent of flame spread by 27 % in 2011. No effect on injuries was found. Within
      each state, effectiveness is moderated by the number of smokers and their
      consumption patterns. In general, FSC cigarettes are more effective in places
      with a large smoking population who engage in heavier smoking. There is a very
      limited effect on the lightest of smokers, suggesting behavioral differences
      between heavy and light smokers that influence fire risk.

PMID- 28751789
TI  - Trends in inequality in length of life in India: a decomposition analysis by age
      and causes of death.
AB  - BACKGROUND: Studies dealing with trends in inequality in length of life in India
      are rare. Studies documenting the contribution of age and causes of death to the
      inequality in length of life are more limited. OBJECTIVE: The study aims to
      examine the trends in inequality in length of life in India and 15 major states
      of India and to decompose the inequality in length of life into the contributions
      of age and causes of death. METHOD: We use life table Gini coefficient (G0) to
      measure the inequality in length of life. We use the formulae developed by
      Shkolnikov, Andreev, and Begun (DR 8(11):305-358, 2003) to decompose the
      differences between Gini coefficients by age and cause of death. RESULT: The G0
      for men has declined from 0.32 in 1981 to 0.19 in 2011. For women, G0 has
      decreased from 0.31 in 1981 to 0.22 in 2011. Mortality decline in the age group 0
      1 year has contributed most to the decrease in G0. In contrast, mortality decline
      in 60+ has tended to increase the G0. The state-wide variations in the age
      specific contributions to decrease in G0 were stark. The contribution of
      noncommunicable diseases to the male-female gap in G0 has increased between 1990
      and 2010. Injuries at ages from 20 to 39 years also contributed to the male
      female difference in G0 in 2010. CONCLUSION: Future studies must analyze
      inequality in life expectancy for assessing the performance of societies
      regarding length of life. CONTRIBUTION: This is the first study that provides
      compelling evidence on inequality in length of life in India and its major
      states.

PMID- 28751790
TI  - Development and evaluation of a leaflet for concerned family members and friends:
      'It's safe to talk about suicide'.
AB  - OBJECTIVES: Significant others can play a key role in suicide prevention, but
      little attention has been given to the resources they may need in order to do so
      effectively. Based on previous qualitative research and working in partnership
      with suicide prevention charities, we developed a simple educational leaflet to
      help family members and friends recognise and respond to a possible suicidal
      crisis. We disseminated 15,000 copies through a wide range of community agencies
      within one English local authority. This paper describes the development,
      distribution and evaluation of the leaflet. The aim of the evaluation was to
      assess how the distribution strategy was working, whether the leaflet was
      regarded as useful and acceptable, how it was being used and whether there were
      any concerns about its content. DESIGN: Interview study. METHODS: We conducted
      two rounds of semi-structured telephone interviews with every agency on the
      distribution list and in-depth qualitative interviews with a purposefully
      selected sub-sample. RESULTS: The leaflet was seen as filling an important gap.
      It was eagerly embraced by staff in frontline agencies, who passed it on to
      clients, used it for their own personal/professional development and to support
      clients or colleagues, or used it as a teaching aid. No concerns were raised
      about its content. CONCLUSION: Findings reveal a deep-seated fear of talking
      about suicide among frontline staff. They were using the leaflet in ways we had
      not anticipated, demonstrating lateral thinking and a real commitment to suicide
      prevention in agencies that are not typically associated with it.

PMID- 28751791
TI  - The development of contemporary European sea bass larvae (Dicentrarchus labrax)
      is not affected by projected ocean acidification scenarios.
AB  - Ocean acidification is a recognized consequence of anthropogenic carbon dioxide
      (CO2) emission in the atmosphere. Despite its threat to marine ecosystems, little
      is presently known about the capacity for fish to respond efficiently to this
      acidification. In adult fish, acid-base regulatory capacities are believed to be
      relatively competent to respond to hypercapnic conditions. However, fish in early
      life stage could be particularly sensitive to environmental factors as organs and
      important physiological functions become progressively operational during this
      period. In this study, the response of European sea bass (Dicentrarchus labrax)
      larvae reared under three ocean acidification scenarios, i.e., control (present
      condition, [Formula: see text] = 590 uatm, pH total = 7.9), low acidification
      (intermediate IPCC scenario, [Formula: see text] = 980 uatm, pH total = 7.7), and
      high acidification (most severe IPCC scenario, [Formula: see text] = 1520 uatm,
      pH total = 7.5) were compared across multiple levels of biological organizations.
      From 2 to 45 days-post-hatching, the chronic exposure to the different scenarios
      had limited influence on the survival and growth of the larvae (in the low
      acidification condition only) and had no apparent effect on the digestive
      developmental processes. The high acidification condition induced both faster
      mineralization and reduction in skeletal deformities. Global (microarray) and
      targeted (qPCR) analysis of transcript levels in whole larvae did not reveal any
      significant changes in gene expression across tested acidification conditions.
      Overall, this study suggests that contemporary sea bass larvae are already
      capable of coping with projected acidification conditions without having to
      mobilize specific defense mechanisms.

PMID- 28751792
TI  - Lead-rich carboxylate-substituted titanium-lead oxo clusters.
AB  - ABSTRACT: The carboxylate-substituted mixed-metal oxo clusters
      Pb6Ti6O9(acetate)(methacrylate)17 and Pb4Ti8O10(OiPr)18(acetate)2 contain a
      higher number of lead atoms in the cluster core than previously reported
      compounds. The metal atoms in both clusters are arranged in three layers of
      different composition, which are connected through oxygen, propionate and/or
      carboxylate bridges. GRAPHICAL ABSTRACT: 

PMID- 28751793
TI  - Aerosol-assisted CVD of thioether-functionalised indium aminoalkoxides.
AB  - ABSTRACT: Thioether-functionalised indium aminoalcoholates have been used as
      single-source precursors in aerosol-assisted CVD processes. The obtained In2O3-x
      S x oxysulphide deposits show either a single indium sulphide phase for deposits
      with high sulphide content [>75% (S/(S + O)) for the t-butyl derivatives] or
      pronounced phase separation in indium oxide and indium sulphide for lower
      sulphide content [<62% (S/(S + O)) for the n-butyl derivatives]. In addition to
      thin films, polycrystalline 1D structures are obtained at slightly modified
      synthesis conditions. The materials are analysed by EDX, XRD, XPS, SEM, and TEM.
      GRAPHICAL ABSTRACT: 

PMID- 28751794
TI  - Crosslinking of floating colloidal monolayers.
AB  - ABSTRACT: Crosslinked colloidal monolayers are promising as templates,
      lithographic masks, filtration membranes, or membranes for controlled release
      rates in drug delivery. We demonstrate assembly of monodisperse micron-sized
      polystyrene (PS) beads at an air/water interface, which are transformed into
      crystalline monolayers using addition of surface-active agents. Vapor annealing
      methods with solvents (toluene and xylene) and crosslinking agents
      (divinylbenzene) were investigated regarding their ability to crosslink these
      floating monolayers directly at the interface, generating crosslinked membranes
      with crystal size up to 44 cm2, domain size up to 1.9 mm2, and nano-sized pores
      (100-300 nm). The demonstrated fabrication method emphasizes short fabrication
      time using a simple setup. GRAPHICAL ABSTRACT: 

PMID- 28751795
TI  - Gender Moderates Association Between Emotional-Behavioral Problems and Text
      Comprehension in Children with Both Reading Difficulties and Adhd.
AB  - Evidence suggests that higher order linguistic functioning such as text
      comprehension is particularly vulnerable to emotional modulation. Gender has been
      identified as an important moderating variable in emotional expression such that
      girls tend toward internalizing emotions (e.g., sadness, anxiety) whereas boys
      tend toward externalizing emotions (e.g., anger, combativeness), which may
      influence the relationship between emotion and text comprehension. The present
      study examined whether gender moderates the relationship between emotional
      behavioral problems and text comprehension among children (n = 187; boys= 115,
      girls = 72) with both word reading difficulties (RD) and attention
      deficit/hyperactivity disorder (ADHD), a sample widely acknowledged to be at
      increased risk for developing emotional-behavioral problems such as anxiety, poor
      academic self-concept, and delinquency. A moderated regression analysis tested
      for the significance of two separate interaction terms (i.e., gender *
      externalizing problems, gender * internalizing problems) after controlling for
      gender, IQ, basic reading skills, cognitive-linguistic processes closely related
      to reading, attentional problems, internalizing problems, and externalizing
      problems. Results indicated that gender significantly and uniquely moderates the
      relationship between emotional-behavioral problems and text comprehension.
      Specifically, text comprehension was relatively lower among girls with relatively
      higher externalizing problems, whereas no such association was observed among
      boys. These results contribute to our understanding of cognition-emotion
      interactions within reading development and raise important implications.

PMID- 28751796
TI  - Calculations of Electron Inelastic Mean Free Paths. XI. Data for Liquid Water for
      Energies from 50 eV to 30 keV.
AB  - We calculated electron inelastic mean free paths (IMFPs) for liquid water from
      its optical energy-loss function (ELF) for electron energies from 50 eV to 30
      keV. These calculations were made with the relativistic full Penn algorithm (FPA)
      that has been used for previous IMFP and electron stopping-power calculations for
      many elemental solids. We also calculated IMFPs of water with three additional
      algorithms: the relativistic single-pole approximation (SPA), the relativistic
      simplified SPA, and the relativistic extended Mermin method. These calculations
      were made using the same optical ELF in order to assess any differences of the
      IMFPs arising from choice of the algorithm. We found good agreement among the
      IMFPs from the four algorithms for energies over 300 eV. For energies less than
      100 eV, however, large differences became apparent. IMFPs from the relativistic
      TPP-2M equation for predicting IMFPs were in good agreement with IMFPs from the
      four algorithms for energies between 300 eV and 30 keV but there was poorer
      agreement for lower energies. We calculated values of the static structure factor
      as a function of momentum transfer from the FPA. The resulting values were in
      good agreement with results from first-principles calculations and with inelastic
      X-ray scattering spectroscopy experiments. We made comparisons of our IMFPs with
      earlier calculations from authors who had used different algorithms and different
      ELF data sets. IMFP differences could then be analyzed in terms of the algorithms
      and the data sets. Finally, we compared our IMFPs with measurements of IMFPs and
      of a related quantity, the effective attenuation length (EAL). There were large
      variations in the measured IMFPs and EALs (as well as their dependence on
      electron energy). Further measurements are therefore required to establish
      consistent data sets and for more detailed comparisons with calculated IMFPs.

PMID- 28751797
TI  - Why Do People with OCD and Health Anxiety Seek Reassurance Excessively? An
      Investigation of Differences and Similarities in Function.
AB  - Excessive reassurance seeking (ERS) is commonly reported in patients who have OCD
      or health anxiety. Despite its prevalence and associated risk of ongoing
      difficulties, little is known about the function of ERS. It has been
      conceptualised as a type of compulsive checking behaviour, but could also be seen
      as being a supportive maneuver. This study offers a new approach towards defining
      ERS and support seeking (SS), and similarities between these two constructs in a
      sample of OCD and health anxious patients. A semi-structured interview was
      employed. Participants reflected on the nature and goals of their reassurance and
      support seeking-its impact on themselves and other people. Twenty interviews were
      conducted, transcribed and analysed in accordance to framework thematic analysis.
      Six overarching themes were identified in terms of ERS and five for SS. Results
      revealed limited diagnosis specificity of ERS. Strikingly, participants with
      health anxiety did not report seeking support.

PMID- 28751798
TI  - A Prospective Investigation of the Impact of Distinct Posttraumatic (PTSD)
      Symptom Clusters on Suicidal Ideation.
AB  - Inconsistent findings have been reported by previous cross-sectional studies
      regarding the association between specific posttraumatic stress disorder (PTSD)
      symptom clusters and suicidality. To advance the understanding of the role of
      specific PTSD symptoms in the development of suicidality, the primary aim of this
      study was to investigate the predictive effects of the three specific PTSD
      symptom clusters on suicidal ideation prospectively. Fifty-six individuals
      diagnosed with PTSD completed a two-stage research design, at baseline and 13-15
      months follow-up. The clinician administered PTSD scale (CAPS) was used to assess
      the severity of the PTSD symptom clusters and validated self-report measures were
      used to assess suicidal ideation, severity of depressive symptoms and perceptions
      of defeat entrapment. The results showed that only the hyperarousal symptom
      cluster significantly predicted suicidal ideation at follow-up after controlling
      for baseline suicidal ideation, severity of depressive symptoms and perceptions
      of defeat and entrapment. These findings suggest that both disorder-specific and
      transdiagnostic factors are implicated in the development of suicidal ideation in
      PTSD. Important clinical implications are discussed in terms of predicting and
      treating suicidality in those with PTSD.

PMID- 28751799
TI  - An Approach to the Estimation of Chronic Air Pollution Effects Using Spatio
      Temporal Information.
AB  - There is substantial observational evidence that long-term exposure to
      particulate air pollution is associated with premature death in urban
      populations. Estimates of the magnitude of these effects derive largely from
      cross-sectional comparisons of adjusted mortality rates among cities with varying
      pollution levels. Such estimates are potentially confounded by other differences
      among the populations correlated with air pollution, for example, socioeconomic
      factors. An alternative approach is to study covariation of particulate matter
      and mortality across time within a city, as has been done in investigations of
      short-term exposures. In either event, observational studies like these are
      subject to confounding by unmeasured variables. Therefore the ability to detect
      such confounding and to derive estimates less affected by confounding are a high
      priority. In this article, we describe and apply a method of decomposing the
      exposure variable into components with variation at distinct temporal, spatial,
      and time by space scales, here focusing on the components involving time.
      Starting from a proportional hazard model, we derive a Poisson regression model
      and estimate two regression coefficients: the "global" coefficient that measures
      the association between national trends in pollution and mortality; and the
      "local" coefficient, derived from space by time variation, that measures the
      association between location-specific trends in pollution and mortality adjusted
      by the national trends. Absent unmeasured confounders and given valid model
      assumptions, the scale-specific coefficients should be similar; substantial
      differences in these coefficients constitute a basis for questioning the model.
      We derive a backfitting algorithm to fit our model to very large spatio-temporal
      datasets. We apply our methods to the Medicare Cohort Air Pollution Study
      (MCAPS), which includes individual-level information on time of death and age on
      a population of 18.2 million for the period 2000-2006. Results based on the
      global coefficient indicate a large increase in the national life expectancy for
      reductions in the yearly national average of PM2.5. However, this coefficient
      based on national trends in PM2.5 and mortality is likely to be confounded by
      other variables trending on the national level. Confounding of the local
      coefficient by unmeasured factors is less likely, although it cannot be ruled
      out. Based on the local coefficient alone, we are not able to demonstrate any
      change in life expectancy for a reduction in PM2.5. We use additional survey data
      available for a subset of the data to investigate sensitivity of results to the
      inclusion of additional covariates, but both coefficients remain largely
      unchanged.

PMID- 28751800
TI  - Light and Temperature Signalling at the Level of CBF14 Gene Expression in Wheat
      and Barley.
AB  - The wheat and barley CBF14 genes have been newly defined as key components of the
      light quality-dependent regulation of the freezing tolerance by the integration
      of phytochrome-mediated light and temperature signals. To further investigate the
      wavelength dependence of light-induced CBF14 expression in cereals, we carried
      out a detailed study using monochromatic light treatments at an inductive and a
      non-inductive temperature. Transcript levels of CBF14 gene in winter wheat
      Cheyenne, winter einkorn G3116 and winter barley Nure genotypes were monitored.
      We demonstrated that (1) CBF14 is most effectively induced by blue light and (2)
      provide evidence that this induction does not arise from light-controlled CRY
      gene expression. (3) We demonstrate that temperature shifts induce CBF14
      transcription independent of the light conditions and that (4) the effect of
      temperature and light treatments are additive. Based on these data, it can be
      assumed that temperature and light signals are relayed to the level of CBF14
      expression via separate signalling routes.

PMID- 28751801
TI  - Drought-Tolerant Brassica rapa Shows Rapid Expression of Gene Networks for
      General Stress Responses and Programmed Cell Death Under Simulated Drought
      Stress.
AB  - Production of oilseed rape/canola (Brassica napus) is increasingly threatened by
      dry conditions while the demand for vegetable oil is increasing. Brassica rapa is
      a genetically diverse ancestor of B. napus, and is readily crossed with B. napus.
      Recently, we reported promising levels of drought tolerance in a wild type of B.
      rapa which could be a source of drought tolerance for B. napus. We analysed
      global gene expression by messenger RNA sequencing in seedlings of the drought
      tolerant and a drought-sensitive genotype of B. rapa under simulated drought
      stress and control conditions. A subset of stress-response genes were validated
      by reverse transcription quantitative PCR. Gene ontology enrichment analysis and
      pathway enrichment analysis revealed major differences between the two genotypes
      in the mode and onset of stress responses in the first 12 h of treatment. Drought
      tolerant plants reacted uniquely and rapidly by upregulating genes associated
      with jasmonic acid and salicylic acid metabolism, as well as genes known to cause
      endoplasmic reticulum stress and induction of programmed cell death. Conversely,
      active responses in drought-sensitive plants were delayed until 8 or 12 h after
      stress application. The results may help to identify biomarkers for selection of
      breeding materials with potentially improved drought tolerance.

PMID- 28751802
TI  - Molecular hydrogen in the treatment of acute and chronic neurological conditions:
      mechanisms of protection and routes of administration.
AB  - Oxidative stress caused by reactive oxygen species is considered a major mediator
      of tissue and cell injuries in various neuronal conditions, including
      neurological emergencies and neurodegenerative diseases. Molecular hydrogen is
      well characterized as a scavenger of hydroxyl radicals and peroxynitrite.
      Recently, the neuroprotective effects of treatment with molecular hydrogen have
      been reported in both basic and clinical settings. Here, we review the effects of
      hydrogen therapy in acute neuronal conditions and neurodegenerative diseases.
      Hydrogen therapy administered in drinking water may be useful for the prevention
      of neurodegenerative diseases and for reducing the symptoms of acute neuronal
      conditions.

PMID- 28751803
TI  - CAPE increases the expression of SOD3 through epigenetics in human retinal
      endothelial cells.
AB  - Extracellular-superoxide dismutase (EC-SOD or SOD3), which catalyzes the
      dismutation of superoxide anions into hydrogen peroxide, plays a key role in
      vascular protection against reactive oxygen species (ROS). The excess generation
      of ROS is closely involved in the pathogenesis of diabetic retinopathy (DR);
      therefore, the maintenance of SOD3 expression at high levels is important for the
      prevention of DR. In the present study, we showed that caffeic acid phenethyl
      ester (CAPE) increased the expression of SOD3 through the acetylation of histone
      within the SOD3 promoter region in human retinal endothelial cells (HRECs).
      Histone acetylation within its promoter was focused on the inhibition of histone
      deacetylase (HDAC), and we examined the involvement of myocyte enhancer factor 2
      (MEF2) and HDAC1 in CAPE-elicited SOD3 expression. Our results demonstrate that
      SOD3 silencing in basal HRECs is regulated by HDAC1 composed with MEF2A/2D hetero
      dimers. Moreover, phosphorylation of threonine 312 in MEF2A and dissociation of
      HDAC1 from SOD3 promoter play pivotal roles in CAPE-elicited SOD3 expression.
      Overall, our findings provide that CAPE may be one of the seed compounds that
      maintain redox homeostasis.

PMID- 28751804
TI  - Antioxidant properties of green tea aroma in mice.
AB  - Green tea ('Sencha'), made from the leaves of Camellia sinensis, is the most well
      researched antioxidant beverage. The major source of its antioxidant activity is
      polyphenols, consisting mainly of catechins (flavan-3-ols). However, little is
      known about the physiological effects of green tea aroma, which lacks catechins.
      In the present study, we performed inhalation experiments with green tea aroma to
      evaluate its antioxidant activity in mice. As a result, the urinary 8
      hydroxydeoxyguanosine levels were significantly decreased in comparison with
      those of the non-treated group, and the serum antioxidant capacity was
      significantly increased by the inhalation administration of green tea aroma.
      Furthermore, the increase in the urinary 8-hydroxydeoxyguanosine levels due to
      whole-body X-ray irradiation was significantly suppressed by the inhalation of
      green tea aroma. This is the first study to show the antioxidant activity of
      green tea aroma in vivo.

PMID- 28751805
TI  - Astaxanthin ameliorates ferric nitrilotriacetate-induced renal oxidative injury
      in rats.
AB  - Daily intake of vegetables can reduce the risk of cancer and lifestyle-related
      diseases. However, supplementary intake of beta-carotene alone has been reported
      to increase the risk of lung cancer in male cigarette smokers and people who were
      exposed to asbestos. The mechanism of the antioxidative properties of carotenoids
      in vivo, especially under oxidative stress conditions, still remains unclear. To
      investigate the antioxidant properties of dietary compounds, we examined the
      effects of chemically modified astaxanthin (Ax-C-8) using a rat model of ferric
      nitrilotriacetate (Fe-NTA)-induced renal oxidative injury. Ax-C-8 demonstrated
      lethally toxic effects on the rats in a dose-dependent manner. Following
      supplementation with Ax-C-8 (0.02%, w/w) for 30 days, the rats were euthanized 1,
      4 and 24 h after injection of Fe-NTA. After 4 h, Ax-C-8 pretreatment suppressed
      the elevation of creatinine and blood urea nitrogen and protected the rats from
      renal tubular necrosis and the formation of 4-hydroxy-2-nonenal-modified
      proteins. After 24 h, pretreatment with Ax-C-8 maintained the renal antioxidant
      enzyme levels and renal tubules. Here, we demonstrate the antioxidant effects of
      Ax-C-8 against Fe-NTA-induced oxidative injury in rats receiving a regular diet.
      These data suggest that dietary intake of astaxanthin may be useful for the
      prevention of renal tubular oxidative damage.

PMID- 28751806
TI  - A marine bio-functional lipid, fucoxanthinol, attenuates human colorectal cancer
      stem-like cell tumorigenicity and sphere formation.
AB  - Fucoxanthinol (FuOH), an intestinal metabolite form of fucoxanthin (Fx) isolated
      from marine algae, is known to possess multiple health benefits, such as
      prevention of human cancer. However, there is little available information about
      the effects of FuOH on colorectal cancer stem cells (CCSCs) and their
      contribution to drug resistance, tumorigenesis and cancer recurrence. In the
      present study, we investigated the anti-proliferative effect of FuOH on two
      putative CCSCs, CD44high/EpCAMhigh cells and colonospheres (Csps) formed by HT-29
      human colorectal cancer cells, and the suppressive effects of FuOH on the growth
      of xenografted tumor. FuOH significantly inhibited the growth of
      CD44high/EpCAMhigh cells and disintegrated Csps and induced many condensed
      chromatin bodies in the cells in a dose-dependent manner. The IC50 value of FuOH
      for these changes in Csps was 1.8 uM. FuOH down-regulated pAkt (Ser473),
      PPARbeta/delta and PPARgamma in Csps. These proteins play a critical role in cell
      proliferation, the cell cycle, metastasis and extracellular adhesion. Ten days
      after the administration of FuOH (5 mg/kg body weight) to the mice every 3 to 4
      days significantly suppressed the Csps tumorigenesis when compared to the
      untreated control mice. Our results suggest that FuOH could be used as a
      chemopreventive agent against human CCSC.

PMID- 28751807
TI  - Protective effects of astaxanthin on skin deterioration.
AB  - Astaxanthin is a carotenoid with potent antioxidant and anti-inflammatory
      activity. To evaluate the anti-inflammatory effect of astaxanthin on skin
      deterioration, we confirmed its role in epidermal-dermal interactions in vitro.
      Astaxanthin treatment suppressed ultraviolet B (UVB)-induced inflammatory
      cytokine secretion in keratinocytes, and matrix metalloproteinase-1 secretion by
      fibroblasts cultured in UVB-irradiated keratinocyte medium. To verify these
      findings, we conducted a 16-week clinical study with 65 healthy female
      participants. Participants were orally administered either a 6 mg or 12 mg dose
      of astaxanthin or a placebo. Wrinkle parameters and skin moisture content
      significantly worsened in the placebo group after 16 weeks. However, significant
      changes did not occur in the astaxanthin groups. Interleukin-1alpha levels in the
      stratum corneum significantly increased in the placebo and low-dose groups but
      not in the high-dose group between weeks 0 and 16. This study was performed in
      Japan from August to December, when changing environmental factors, such as UV
      and dryness, exacerbate skin deterioration. In conclusion, our study suggests
      that long-term prophylactic astaxanthin supplementation may inhibit age-related
      skin deterioration and maintain skin conditions associated with environmentally
      induced damage via its anti-inflammatory effect. (UMIN Clinical Trials Registry
      ID: UMIN000018550).

PMID- 28751808
TI  - Relationship between hyposalivation and oxidative stress in aging mice.
AB  - The increase in oxidative stress that accompanies aging has been implicated in
      the abnormal advance of aging and in the onset of various systemic diseases.
      However, the details of what effects the increase in oxidative stress that
      accompanies aging has on saliva secretion are not known. In this study, naturally
      aging mice were used to examine the stimulated whole saliva flow rate, saliva and
      serum oxidative stress, antioxidant level, submandibular gland H-E staining, and
      immunofluorescence staining to investigate the effect of aging on the volume of
      saliva secretion and the relationship with oxidative stress, as well as the
      effect of aging on the structure of salivary gland tissue. The stimulated whole
      saliva flow rate decreased significantly with age. Also, oxidative stress
      increased significantly with age. Antioxidant levels, however, decreased
      significantly with age. Structural changes of the submandibular gland
      accompanying aging included atrophy of parenchyma cells and fatty degeneration
      and fibrosis of stroma, and the submandibular gland weight ratio decreased. These
      results suggest that oxidative stress increases with age, not just systemically
      but also locally in the submandibular gland, and that oxidative stress causes
      changes in the structure of the salivary gland and is involved in hyposalivation.

PMID- 28751809
TI  - Intake of mulberry 1-deoxynojirimycin prevents colorectal cancer in mice.
AB  - The effect of 1-deoxynojirimycin, a caloric restriction mimetic, was examined in
      ICR mice with azoxymethane dextran sodium sulfate-induced colorectal cancer.
      Azoxymethane is a carcinogen (10 mg/kg body weight), and 2% dextran sodium
      sulfate (w/v) used as a colitis-inducing agent. Mice were separated into 5
      groups: a group without colorectal cancer fed a normal diet (CO- group), and
      groups with colorectal cancer fed a normal diet (CO+ group), a calorie-restricted
      diet (caloric restriction group), and diets including 0.02% and 0.1% 1
      deoxynojirimycin (l-1-deoxynojirimycin and H-1-deoxynojirimycin groups). The
      tumor incidence and number were reduced significantly in the caloric restriction
      group compared to the CO+ group, and were also suppressed in a dose-dependent
      manner by 1-deoxynojirimycin. mRNA for anti-apoptotic Bcl-2 was decreased and
      that for pro-apoptotic Bax was increased in the carcinoma tissue of CR, l-1
      deoxynojirimycin and H-1-deoxynojirimycin groups. These results suggest that
      caloric restriction and 1-deoxynojirimycin inhibit growth of colorectal cancer by
      inducing apoptosis in an induced cancer model in mice.

PMID- 28751810
TI  - Effectiveness of tolvaptan monotherapy and low-dose furosemide/tolvaptan
      combination therapy for hepatoprotection and diuresis in a rat cirrhotic model.
AB  - Spironolactone and furosemide, which are used to treat ascites associated with
      decompensated cirrhosis, are ineffective in treating refractory ascites. Hence,
      combination therapy with tolvaptan, a vasopressin V2 receptor antagonist, has
      been approved in Japan. Tolvaptan monotherapy and combination therapy with
      furosemide inhibit fibrosis in cardiac remodeling; hence, we examined these
      therapies in a rat cirrhotic model, including their usefulness in inhibiting
      hepatic fibrosis. In the present study, we used a model of hepatic fibrosis
      induced by a choline-deficient l-amino-acid-defined diet + diethylnitrosamine.
      Rats were divided into a low-dose furosemide group (15 mg/kg/day), a high-dose
      furosemide group (100 mg/kg/day), a tolvaptan monotherapy group (10 mg/kg/day), a
      low-dose furosemide/tolvaptan combination therapy group, and a control group
      which received neither furosemide nor tolvaptan; we then assessed diuretic
      effects and hepatic fibrosis. The tolvaptan monotherapy group and the
      furosemide/tolvaptan combination therapy group demonstrated significantly higher
      urine volume than the control group and the low-dose furosemide group. In
      addition, tolvaptan monotherapy and low-dose furosemide/tolvaptan combination
      therapy were found to inhibit hepatic fibrosis and yield a hepatoprotective
      effect by an antioxidative mechanism. The results of the present study suggest
      that tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy
      are highly effective for hepatoprotection and diuresis.

PMID- 28751811
TI  - The association between serum ferritin and 25-hydroxyvitamin D and metabolic
      syndrome in Korean women: the Korea National Health and Nutrition Examination
      Survey 2010-2012.
AB  - The present study was conducted to assess the association between serum ferritin
      and 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome (MetS) in Korean women.
      The data of a total of 9,256 adults (6,960 women without MetS and 2,296 women
      with MetS) aged >=20 years from the Fifth Korean National Health and Nutrition
      Examination Survey (KNHANES V) (2010-2012) were analyzed. A covariance test
      adjusted for covariates was performed for serum ferritin levels in relation to
      vitamin D (vitamin D deficiency, 25(OH)D <10.0 ng/ml; vitamin D insufficiency,
      25(OH)D >=10.0, <20.0 ng/ml; vitamin D sufficiency, 25(OH)D >=20.0 ng/ml). The
      key study results were as follows: First, in women without MetS, after adjusting
      for related variables (smoking, alcohol drinking, regular exercise, current
      menstruation, hormonal contraceptives, hormone-replacement therapy, SBP, DBP,
      BMI, WM, TC, TGs, HDL-C, FPG, AST, ALT, and age), vitamin D was positively
      associated with serum ferritin levels (p<0.001). Second, in women with MetS,
      after adjusting for related variables (except age), vitamin D was positively
      associated with serum ferritin levels (p = 0.041). However, when further adjusted
      for age, vitamin D was not associated with serum ferritin levels (p = 0.293). In
      conclusion, vitamin D was positively associated with serum ferritin levels in
      women without MetS but not in women with MetS.

PMID- 28751812
TI  - Maslinic acid improves quality of life by alleviating joint knee pain in the
      elderly: results from a community-based pilot study.
AB  - Chronic knee joint pain is common in the elderly and associated with poor quality
      of life. This study, an open-label clinical trial, aimed to examine how the
      intake on a daily basis of maslinic acid-containing product (30 mg maslinic acid)
      on 29 elderly residents (mean 70.7 +/- 10.1 years) of Nakajima Island, Ehime,
      Japan. Study participants consumed 10 g jelly containing maslinic acid daily for
      16 weeks and at 0 (baseline), 4, 8, 12 and 16 weeks, assessed for health-related
      quality of life (Short Form-8) and knee pain score (Japanese Knee Osteoarthritis
      Measure). After 16 weeks, the physical quality of life, more specifically, the
      level of Bodily Pain and Physical Component Summary, but not mental quality of
      life, was significantly improved by maslinic acid intake. Furthermore, maslinic
      acid intake significantly decreased the Japanese Knee Osteoarthritis Measure at
      week 8 and tended to decrease Visual Analogue Scale score at weeks 4 and 16.
      These results suggest that consumption of maslinic acid has a protective effect
      against chronic knee pain in elderly residents in a community where knee pain
      causes high quality of life burden.

PMID- 28751813
TI  - Urinary pH reflects dietary acid load in patients with type 2 diabetes.
AB  - Dietary acid load is important information, however, survey of food intake needs
      time and skill. Therefore, it is difficult to survey food intake from all
      patients. It remains to be elucidated the association between dietary acid load
      and urinary pH in patients with type 2 diabetes. In this cross-sectional study of
      173 patients, we investigated the relationship between urinary pH and dietary
      acid load, assessed with potential renal acid load. Habitual food and nutrient
      intake was assessed by a self-administered diet history questionnaire. Urinary pH
      was negatively correlated with potential renal acid load (r = -0.24, p = 0.002).
      Multivariate regression analysis revealed that potential renal acid load
      (standardized regression coefficient = -0.21, p = 0.036) was associated with
      urinary pH after adjusting for covariates. In addition, according to the receiver
      operator characteristic analysis, the optimal cut-off point of urinary pH for
      high dietary acid load, defined as potential renal acid load over 7.0 mEq/day was
      5.7 (area under the receiver operator characteristic curve 0.63 (95% CI 0.54
      0.71), sensitivity = 0.56, specificity = 0.70, p = 0.004). Urinary pH was
      associated with dietary acid load in patients with type 2 diabetes. We suggest
      that urinary pH can be a practical screening marker for dietary acid load in
      patients with type 2 diabetes.

PMID- 28751814
TI  - Concept of Phase Cycling in Pulsed Magnetic Resonance Using Sinusoidal Magnetic
      Field Modulation.
AB  - In conventional pulsed magnetic resonance suppression of unwanted signals is
      achieved by changing pulse phases with respect to the reference signal and spin
      magnetization phase. This method is called phase cycling. An alternative approach
      is suggested to separate the unwanted signals from the spin echo by using
      magnetic field modulation. Precession frequency of the spins, and therefore
      phases of free indication decays and echo signals, can be controlled by the
      selection of modulation parameters. This enables phase cycling. Since the signal
      is detected in the presence of the changing magnetic field, which drives spin
      precession, the echo signal is frequency-modulated. Numerical transformation into
      an accelerating reference frame associated with the Larmor frequency restores the
      signal to a form that would have been observed in the absence of modulation. The
      suggested phase cycling method is analyzed in detail for the two pulse spin echo
      case.

PMID- 28751815
TI  - 'Elderly years cause a Total dispaire of Conception': Old Age, Sex and
      Infertility in Early Modern England.
AB  - Although the history of old age has been studied in much greater detail in recent
      years, the subject of sexuality in old age remains relatively under-explored.
      This article examines early modern ideas about old bodies and sex in relation to
      fertility, to argue that because old bodies were understood as either infertile
      (post-menopausal women) or sub-fertile (old men) they were therefore
      characterised as unsuitable, undesirable and inappropriate sexual partners.
      Perceptions of old bodies, their sexual abilities, desirability and behaviour
      were remarkably consistent from the sixteenth through to the eighteenth century.
      The ridiculing of old men and women's sexual behaviour that permeated
      contemporary culture in stories, ballads and jokes, alongside medical literature
      that characterised old bodies as sexually unappetising as well as unreproductive,
      carried the message that sexual activity was not for the old, and in large part
      because they were infertile.

PMID- 28751816
TI  - Harnessing the Power of Difference: Colonialism and British Chronic Disease
      Research, 1940-1975.
AB  - Recent studies of post-war chronic disease epidemiology have generally focused on
      the histories of research in the USA and UK. Using the archival records of a
      major British funding body, the Colonial Medical Research Committee and its
      successor the Tropical Medical Research Board, this article demonstrates the
      advantages of bringing a post-colonial analytic to this historiography. It
      highlights how the administrative and medical interests in population difference
      at the centre of the new epidemiology came to map onto political apparatus
      initially created to know, reform and govern colonial subjects. Although detached
      from imperial aims, British medical scientists nonetheless attached value to
      colonial populations on the basis of British benefit and turned various sites
      into laboratories to extract it. This relationship did not die with the end of
      imperial rule. British scientists continued to pursue chronic disease
      epidemiology in former colonies well into the post-war period, informing debates
      about Britain's own public health concerns.

PMID- 28751817
TI  - Campaigning on the welfare state: The impact of gender and gender diversity.
AB  - Social policy matters have long been considered women's issues. Extant research
      has documented a strong link between gender and the policies of the welfare state
      in the legislative, executive and electoral arenas. Yet what determines the
      strength of this association has largely been left unexplored. Drawing on
      tokenism theory, this article proposes gender diversity at the group level as a
      key explanatory factor. It hypothesizes that the gender gap in social policy
      diminishes as the female representation in a political party increases. To test
      this argument, it examines almost 8000 press releases issued by over 600
      politicians during four election campaigns in Austria between 2002 and 2013. The
      analysis demonstrates that women talk more about social policy issues during
      election campaigns than men, but that this emphasis gap disappears for parties
      with a more equal gender balance. These results have important implications for
      our understanding of the politics of gender and social policy.

PMID- 28751818
TI  - Identifying Mother-Child Interaction Styles Using a Person-Centered Approach.
AB  - Parent-child conflict in the context of a supportive relationship has been
      discussed as a potentially constructive interaction pattern; the current study is
      the first to test this using a holistic analytic approach. Interaction styles,
      defined as mother-child conflict in the context of maternal sensitivity, were
      identified and described with demographic and stress-related characteristics of
      families. Longitudinal associations were tested between interaction styles and
      children's later social competence. Participants included 814 partnered mothers
      with a first-grade child. Latent profile analysis identified agreeable, dynamic,
      and disconnected interaction styles. Mothers' intimacy with a partner, depressive
      symptoms, and authoritarian childrearing beliefs, along with children's later
      conflict with a best friend and externalizing problems, were associated with
      group membership. Notably, the dynamic style, characterized by high sensitivity
      and high conflict, included families who experienced psychological and relational
      stressors. Findings are discussed with regard to how family stressors shape
      parent-child interaction patterns.

PMID- 28751819
TI  - Effects of Secreted Mast Cell Mediators on Retinal Pigment Epithelial Cells:
      Focus on Mast Cell Tryptase.
AB  - Numerous mast cells are present in the choroid, but the effects of mast cell
      mediators on retinal pigment epithelial (RPE) cells are not well understood. We
      investigated the influence of mast cell mediators on RPE cells in vitro, focusing
      on tryptase. Expression of receptors was examined by the reverse transcription
      polymerase chain reaction. We also assessed production of interleukin 8 and
      vascular endothelial growth factor (VEGF) after RPE cells were stimulated with
      mast cell mediators by using an antibody array and enzyme-linked immunosorbent
      assay. Furthermore, we investigated the influence of tryptase on RPE cell
      migration and integrity by the scratch assay and the transepithelial resistance.
      RPE cells expressed protease-activated receptor 2 (PAR2), histamine receptor 1,
      tumor necrosis factor-alpha (TNF-alpha) receptor 1, and CCR 1, 3, 4, 8, and 11.
      Tryptase, PAR2 agonists, histamine, and TNF-alpha all enhanced interleukin 8
      production by RPE cells, while only tryptase enhanced VEGF production. Tryptase
      also enhanced expression of phosphorylated extracellular signal-regulated kinases
      1/2, resulting in increased migration of RPE cells. However, tryptase did not
      alter epithelial integrity or the expression of zonula occludens-1 and junctional
      adhesion molecule-A by RPE cells. Mast cell mediators, especially tryptase, may
      influence RPE cell inflammation.

PMID- 28751820
TI  - Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute
      Colitis in Mice and the Production of Inflammatory Mediators from Macrophages.
AB  - We recently reported the immune-enhancing effects of a high-molecular-weight
      fraction (HMF) of CW in macrophages and immunosuppressed mice, and this effect
      was attributed to a crude polysaccharide. As polysaccharides may also have anti
      inflammatory functions, we investigated the anti-inflammatory effects and related
      molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in
      mice with dextran sulfate sodium- (DSS-) induced colitis and in
      lipopolysaccharide-induced RAW 264.7 macrophages. HMFO ameliorated the
      pathological characteristics of colitis and significantly reduced production of
      proinflammatory cytokines in the serum. Histological analysis indicated that HMFO
      improved the signs of histological damage such as abnormal crypts, crypt loss,
      and inflammatory cell infiltration induced by DSS. In addition, HMFO inhibited
      iNOS and COX-2 protein expression, as well as phosphorylated NF-kappaB p65 levels
      in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO
      inhibited several cytokines and enzymes involved in inflammation such as
      prostaglandin E2, nitric oxide, tumor necrosis factor-alpha, interleukin-6,
      inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear
      factor-kappaB (NF-kappaB) and mitogen-activated protein kinases. HMFO attenuated
      inflammation both in vitro and in vivo, primarily by inhibiting NF-kappaB
      activation. Our findings indicate that HMFO is a promising remedy for treating
      inflammatory bowel diseases, such as colitis.

PMID- 28751821
TI  - Immunomodulation of RA Patients' PBMC with a Multiepitope Peptide Derived from
      Citrullinated Autoantigens.
AB  - Citrullinated peptides are used for measuring anticitrullinated protein
      antibodies (ACPA) in rheumatoid arthritis (RA). Accumulation of citrullinated
      proteins in the inflamed synovium suggests that they may be good targets for
      inducing peripheral tolerance. In view of the multiplicity of citrullinated
      autoantigens described as ACPA targets, we generated a multiepitope citrullinated
      peptide (Cit-ME) from the sequences of major citrullinated autoantigens:
      filaggrin, beta-fibrinogen, vimentin, and collagen type II. We assessed the
      ability of Cit-ME or the citrullinated beta60-74 fibrinogen peptide (beta60-74
      Fib-Cit) which bears immunodominant citrullinated epitopes (i) to modify cytokine
      gene expression and (ii) to modulate Treg and Th17 subsets in PBMC derived from
      newly diagnosed untreated RA patients. RA patient's PBMC incubated with Cit-ME or
      beta60-74-Fib-Cit, showed upregulation of TGF-beta expression (16% and 8%,
      resp.), and increased CD4+Foxp3+ Treg (22% and 19%, resp.). Both peptides were
      shown to downregulate the TNF-alpha and IL-1beta expression; in addition, Cit-ME
      reduced CD3+IL17+ T cells. We showed that citrullinated peptides can modulate the
      expression of anti- and proinflammatory cytokines in PBMC from RA patients as
      well as the proportions of Treg and Th17 cells. These results indicate that
      citrullinated peptides could be active in vivo and therefore might be used as
      immunoregulatory agents in RA patients.

PMID- 28751822
TI  - Vitamin D Deficiency Is Associated with Increased Osteocalcin Levels in Acute
      Aortic Dissection: A Pilot Study on Elderly Patients.
AB  - An imbalance between degradation and reconstruction of the aortic wall is one of
      the leading causes of acute aortic dissection (AAD). Vitamin D seems an
      intriguing molecule to explore in the field of AAD since it improves endothelial
      function and protects smooth muscle cells from inflammation-induced remodeling,
      calcification, and loss of function, all events which are strongly related to the
      aging process. We quantified 25-hydroxy vitamin D, calcium, parathormone, bone
      alkaline phosphatase, and osteocalcin levels in 24 elderly AAD patients to
      identify a potential pathological implication of these molecules in AAD. Median
      25-hydroxy vitamin D (10.75 ng/mL, 25th-75th percentiles: 6.86-19.23 ng/mL) and
      calcium levels (8.70 mg/dL, 25th-75th percentiles: 7.30-8.80 mg/dL) suggested
      hypovitaminosis D and a moderate hypocalcemia. Thirty-eight percent of AAD
      patients had severe (<10 ng/mL), 38% moderate (10-20 ng/mL), and 24% mild 25
      hydroxy vitamin D deficiency (20-30 ng/mL). A significant inverse correlation was
      observed between 25OHD and osteocalcin levels. All the other molecules were
      unchanged. A condition of hypovitaminosis D associated to an increase in
      osteocalcin levels is present in AAD patients. The identification of these
      molecules as new factors involved in AAD may be helpful to identify individuals
      at high risk as well to study preventing strategies.

PMID- 28751823
TI  - Global Autorecognition and Activation of Complement by Mannan-Binding Lectin in a
      Mouse Model of Type 1 Diabetes.
AB  - Increasing evidence links mannan-binding lectin (MBL) to late vascular
      complications of diabetes. MBL is a complement-activating pattern recognition
      molecule of the innate immune system that can mediate an inflammation response
      through activation of the lectin pathway. In two recent animal studies, we have
      shown that autoreactivity of MBL is increased in the kidney in diabetic
      nephropathy. We hypothesize that long-term exposure to uncontrolled high blood
      glucose in diabetes may mediate formation of neoepitopes in several tissues and
      that MBL is able to recognize these structures and thus activate the lectin
      pathway. To test this hypothesis, we induced diabetes by injection of low-dose
      streptozotocin in MBL double-knockout (MBL/DKO) mice. Development of diabetes was
      followed by measurements of blood glucose and urine albumin-to-creatinine ratio.
      Fluorophore-labelled recombinant MBL was injected intravenously in diabetic and
      nondiabetic mice followed by ex vivo imaging of several organs. We observed that
      MBL accumulated in the heart, liver, brain, lung, pancreas, and intestines of
      diabetic mice. We furthermore detected increased systemic complement activation
      after administration of MBL, thus indicating MBL-mediated systemic complement
      activation in these animals. These new findings indicate a global role of MBL
      during late diabetes-mediated vascular complications in various tissues.

PMID- 28751824
TI  - Face race processing and racial bias in early development: A perceptual-social
      linkage.
AB  - Infants have asymmetrical exposure to different types of faces (e.g., more human
      than other-species, more female than male, and more own-race than other-race).
      What are the developmental consequences of such experiential asymmetry? Here we
      review recent advances in research on the development of cross-race face
      processing. The evidence suggests that greater exposure to own- than other-race
      faces in infancy leads to developmentally early perceptual differences in visual
      preference, recognition, category formation, and scanning of own- and other-race
      faces. Further, such perceptual differences in infancy may be associated with the
      emergence of implicit racial bias, consistent with a Perceptual-Social Linkage
      Hypothesis. Current and future work derived from this hypothesis may lay an
      important empirical foundation for the development of intervention programs to
      combat the early occurrence of implicit racial bias.

PMID- 28751825
TI  - A smoothing inexact Newton method for variational inequalities with nonlinear
      constraints.
AB  - In this paper, we propose a smoothing inexact Newton method for solving
      variational inequalities with nonlinear constraints. Based on the smoothed
      Fischer-Burmeister function, the variational inequality problem is reformulated
      as a system of parameterized smooth equations. The corresponding linear system of
      each iteration is solved approximately. Under some mild conditions, we establish
      the global and local quadratic convergence. Some numerical results show that the
      method is effective.

PMID- 28751826
TI  - Conformable fractional Dirac system on time scales.
AB  - We study the conformable fractional (CF) Dirac system with separated boundary
      conditions on an arbitrary time scale [Formula: see text]. Then we extend some
      basic spectral properties of the classical Dirac system to the CF case.
      Eventually, some asymptotic estimates for the eigenfunction of the CF Dirac
      eigenvalue problem are obtained on [Formula: see text]. So, we provide a
      constructive procedure for the solution of this problem. These results are
      important steps to consolidate the link between fractional calculus and time
      scale calculus in spectral theory.

PMID- 28751827
TI  - HIV is always with me: men living with perinatally acquired HIV and planning
      their families.
AB  - Once expected to not survive childhood, youth with perinatally-acquired HIV have
      now reached young adulthood are of reproductive age and sexually active. Given
      the health impact of pregnancy among YPHIV, understanding reproductive decision
      making may inform preconception counseling strategies. Most literature regarding
      reproductive health among YPHIV focuses on women, overlooking one of the most
      important factors influencing the reproductive decision making process, male
      sexual partners. This manuscript examined attitudes, perceptions and experiences
      of young men with perinatally-acquired HIV (YMPHIV) regarding family planning and
      relationships, safer sex, disclosure, stigma and psychological health.
      Participants (n = 21) were YMPHIV aged 18-24 recruited in Miami, Florida. Focus
      groups (n = 4) were conducted; qualitative data were analyzed using grounded
      theory. HIV disclosure, stigma, fertility intentions, safer preconception
      knowledge, attitudes and practices, family planning communication with medical
      providers and family, and mental health emerged as themes. Results suggest that
      despite accurate knowledge regarding healthy preconception practices,
      psychopathology, substance use, and stigma, impact the uptake of HIV healthcare
      interventions. Effective interventions on preconception counseling may require
      more tailored approaches than knowledge-based psychoeducation alone, such as
      inclusion of psychological treatment, which could be offered in HIV healthcare
      settings to optimize health outcomes.

PMID- 28751828
TI  - Do Bilingual advantages in attentional control influence memory encoding during a
      divided attention task?
AB  - The current study examined if bilingual advantages in cognitive control influence
      memory encoding during a divided attention task. Monolinguals, simultaneous
      bilinguals, and sequential bilinguals switched between classifying objects and
      words, then were tested for their recognition memory of stimuli previously seen
      during the classification task. Compared to bilingual groups, monolinguals made
      the most errors on the classification task and simultaneous bilinguals committed
      the fewest errors. On the memory task, however, no differences were found between
      the three language groups, but significant correlations were found between the
      number of errors during switch trials on the classification task and recognition
      memory for both target and non-target stimuli. For bilinguals, their age of
      second language acquisition partially accounted for the association between
      attentional control (number of switch errors) and subsequent memory for non
      target stimuli only. These results contribute to our understanding of how
      individual differences in language acquisition influence interactions between
      cognitive domains.

PMID- 28751829
TI  - Relationship between serum angiopoietin-like protein 2 and plaque vulnerability
      in patients with coronary artery disease and diabetes.
AB  - AIMS: Obesity is characterized by low-grade inflammation state and excessive
      inflammatory cytokine production of adipose tissue. Angiopoietin-like protein 2
      (ANGPTL2), a novel proinflammatory adipokine, has recently been suggested to be
      involved in the pathogenesis of atherosclerosis in animal studies. However, no
      data regarding the relationship between ANGPTL2 and morphologic characteristics
      of coronary plaques in humans are available. The aim of the current study was to
      investigate the in vivo association between serum ANGPTL2 level and plaque
      vulnerability in patients with coronary artery disease (CAD) and diabetes.
      METHODS AND RESULTS: 72 consecutive patients with clinically proven CAD and
      diabetes were enrolled between October 2013 and December 2014. Circulating
      ANGPTL2 concentration was measured using a human ANGPTL2 sandwich enzyme-linked
      immunosorbent assay (ELISA) kit. The morphologic characteristics of non-culprit
      lipid-rich plaques were assessed by optical coherence tomography. Fibrous cap
      thickness was significantly and negatively correlated with serum ANGPTL2 levels
      (r = -0.29, P = 0.005). A significant and positive correlation was observed
      between mean lipid core arc and serum ANGPTL2 concentration (r = 0.32, P = 0.01).
      In addition, levels of serum ANGPTL2 were significantly higher in patients with
      thin-cap fibroatheroma (TCFA) than those without TCFA (P < 0.001). Multivariate
      logistic regression analysis showed that a higher serum ANGPTL2 concentration was
      a powerful predictor of TCFA (odds ratio: 3.18, P = 0.002). CONCLUSION: Serum
      ANGPTL2 level is significantly associated with plaque vulnerability in patients
      with CAD and diabetes. Systemic ANGPTL2 comprises an inflammatory adipokine that
      links the adipose tissue and coronary plaque.

PMID- 28751830
TI  - Relationship between Serum fibroblast growth factor 21 levels and morphological
      atherosclerotic plaque characteristics in patients with coronary heart disease.
AB  - AIMS: Fibroblast growth factor (FGF) 21, as an important regulator for systemic
      glucose and lipid metabolism, has recently been demonstrated to be associated
      with atherosclerosis, but the relationship between serum FGF21 and
      characteristics of atherosclerotic plaques remains unclear. The aims of the
      current study were to evaluate the association between serum FGF21 and
      morphological characteristics of atherosclerotic plaques in vivo. METHODS AND
      RESULTS: Overall, 68 patients with coronary heart disease were evaluated by
      virtual histology-intravascular ultrasound, and circulating FGF21 concentration
      were measured by enzyme-linked immunosorbent assay. Serum FGF21 levels showed a
      significant and positive correlation with plaque burden (plaque+media divided by
      external elastic membrane) (r = 0.28, P = 0.01). Conversely, serum FGF21 levels
      in patients with VH thin-cap fibroatheroma were lower than those with VH thick
      cap fibroatheroma (P < 0.01). CONCLUSION: Serum FGF21 is positively correlated
      with atherosclerotic plaque burden, and interestingly, the high level of serum
      FGF21 may represent a positive response to atherosclerosis.

PMID- 28751831
TI  - Water-soluble chitosan regulates vascular remodeling in hypertension via NFATc1.
AB  - OBJECTIVE: Hypertension is a public health problem in the world, and the
      disability and mortality rate is extremely high. Its important pathology
      foundation is vascular remodeling. Water-soluble chitosan (WSC) is the
      degradation product of chitosan, and have a role to control hypertension. The
      present study aims to investigate the regulatory effects of WSC on vascular
      remodeling in hypertension, and further to confirm the roles of nuclear factor c1
      of activatied T cells (NFATc1) during this effect. METHODS: Primary cultured rat
      abdominal aortic smooth muscle cells were incubated with PBS, AngII, and AngII +
      WSC (0.1 mg/L) for 24 h. MTT and western blot methods were applied to analyzed
      the cell proliferation and c-myc protein expression, respectively, among all
      experimental groups. Successfully established spontaneously hypertensive Wistar
      kyoto rats (SHR) were divided into two groups randomly: SHR group (n = 30) and
      SHR + WSC group (n = 30,WSC150 mg/kg/d). Another 15 Wistar-kyoto rats treated
      with PBS were served as control group. At the end of the experiments, the
      hemodynamic changes were analyzed using rat tail arterial pressure measuring
      instrument. H&E staining was performed to observe the morphological changes of
      abdominal aorta. Furthermore, immunohistochemical method, western blot and real
      time quantitative PCR were applied to detected the expression of NAFTc1 protein
      and mRNA. RESULTS: WSC significantly reduced the cell viability in primary
      cultured rat abdominal aortic smooth muscle cells compare with PBS and AngII
      treated cells. Compared with PBS group, the enhanced expression level of c-myc
      protein was observed in AngII-treated cells, which was significantly blocked by
      WSC incubation. Compared with control rats, the abnormally high blood pressure
      and membrane thickness/lumen diameter ratio of abdominal aorta were noted in SHR
      model rats, which strongly reduced after WSC administration. Hypertension
      resulted in an increment on expression of both NFATc1 protein and mRNA in
      abdominal aorta of Wistar-kyoto rats compared with control groups. Encouragingly,
      WSC strikingly suppressed the high levels of NFATc1 protein and even mRNA.
      CONCLUSION: In both cell and animal experiments, we succefully confirmed the
      regulatory effects of WSC on vascular remodeling in hypertension. Based on the
      present results, WSC-inhibited vascular remodeling may be related to the
      modulation on NFATc1 expression. Our experiment provides a solid basis for the
      clinical application of WSC on hypertension.

PMID- 28751832
TI  - Relation between serum calcium levels and mortality in patients with coronary
      artery disease.
AB  - OBJECTIVES: Calcium has a critical role in a spectrum of biological processes
      related to cardiovascular disease. This study aimed to evaluate associations of
      baseline serum calcium levels with both short-term and long-term outcomes in CAD
      patients. MATERIALS AND METHODS: 3109 consecutive patients with angiography
      confirmed CAD, admitted to West China hospital of Sichuan University between July
      2008 and September 2012 were enrolled and were categorized into quartiles
      according to admission serum calcium to determine the association of serum
      calcium level with in-hospital and long-term mortality by multivariable Logistic
      and Cox regression analysis respectively. RESULTS: The admission serum calcium
      was normally distributed with a mean level of 2.20+/-0.15 mmol/L. A total of 259
      deaths, including 58 in-hospital deaths, occurred during a mean follow-up of 20
      months. Patients in the upper quartiles of serum calcium, as compared to the
      lowest quartile of serum calcium, were presented with lower in-hospital mortality
      [HR was 0.391 (95% CI: 0.188-0.812), 0.231(95% CI: 0.072-0.501) and 0.223 (95%
      CI: 0.093-0.534) for three upper quartiles versus lowest quartile respectively]
      and long-term mortality [HR was 0.614 (95% CI: 0.434-0.869), 0.476(95% CI: 0.294
      0.698) and 0.553 (95% CI: 0.349-0.777) respectively]. Similar association between
      serum calcium and long-term mortality as showed in total cohort were also
      obtained when restricting analyses to subgroups: stable CAD patients, ACS
      patients and discharged patients. CONCLUSIONS: As a widely available clinical
      index, serum calcium was an independent predictor of both in-hospital and long
      term mortality among CAD patients. Further studies are warranted to determine
      mechanisms and whether patients with hypocalcaemia could benefit from calcium
      supplement.

PMID- 28751834
TI  - ANMCO Position Paper: diagnostic-therapeutic pathway in patients with
      hypercholesterolaemia and statin intolerance.
AB  - Statins are a class of drugs used to lower total and low-density lipoprotein
      (LDL)-cholesterol. Clinical trials performed over the last 25 years have shown
      that these agents are effective in improving cardiovascular outcomes in several
      different clinical settings. However, in some cases statin treatment may be
      associated with significant side effects and adverse reactions. The occurrence of
      these adverse events during statin therapy may cause discontinuation of
      treatment, and hence the impossibility of achieving recommended lipid goals. The
      clinical condition in which patients experience major unacceptable symptoms
      and/or develop laboratory abnormalities during statin therapy is defined as
      statin intolerance. This document outlines the diagnostic and therapeutic
      pathways for the clinical management of patients with hypercholesterolaemia and
      statin intolerance.

PMID- 28751835
TI  - ANMCO Scientific Statement: clinical management of hypercholesterolaemia in
      patients with acute coronary syndromes.
AB  - LDL cholesterol (LDL-C) reduction after Acute Coronary Syndromes (ACS) is
      associated with a significant decrease in subsequent atherosclerotic
      cardiovascular events. Accordingly, international guidelines recommend a
      reduction of LDL-C below 70 mg/dL in ACS patients. Such a result can be
      effectively accomplished in most cases by using high intensity statins. In
      selected cases, the association with ezetimibe may be necessary in order to
      achieve recommended LDL-C targets. This document outlines management strategies
      that can be consistently implemented in clinical practice in order to achieve and
      maintain guidelines recommended therapeutic goals.

PMID- 28751833
TI  - ANMCO/ISS/AMD/ANCE/ARCA/FADOI/GICR-IACPR/SICI
      GISE/SIBioC/SIC/SICOA/SID/SIF/SIMEU/SIMG/SIMI/SISA Joint Consensus Document on
      cholesterol and cardiovascular risk: diagnostic-therapeutic pathway in Italy.
AB  - Atherosclerotic cardiovascular disease still represents the leading cause of
      death in Western countries. A wealth of scientific evidence demonstrates that
      increased blood cholesterol levels have a major impact on the outbreak and
      progression of atherosclerotic plaques. Moreover, several cholesterol-lowering
      pharmacological agents, including statins and ezetimibe, have proved effective in
      improving clinical outcomes. This document focuses on the clinical management of
      hypercholesterolaemia and has been conceived by 16 Italian medical associations
      with the support of the Italian National Institute of Health. The authors discuss
      in detail the role of hypercholesterolaemia in the genesis of atherosclerotic
      cardiovascular disease. In addition, the implications for high cholesterol levels
      in the definition of the individual cardiovascular risk profile have been
      carefully analysed, while all available therapeutic options for blood cholesterol
      reduction and cardiovascular risk mitigation have been explored. Finally, this
      document outlines the diagnostic and therapeutic pathways for the clinical
      management of patients with hypercholesterolaemia.

PMID- 28751836
TI  - ANMCO Position Paper: direct oral anticoagulants for stroke prevention in atrial
      fibrillation: clinical scenarios and future perspectives.
AB  - It is now 4 years since the introduction of the new direct oral anticoagulants
      into clinical practice. Therefore, the Italian Association of Hospital
      Cardiologists (ANMCO) has deemed necessary to update the previous position paper
      on the prevention of thrombo-embolic complications in patients with non-valvular
      atrial fibrillation, which was published in 2013. All available scientific
      evidence has been reviewed, focusing on data derived from both clinical trials
      and observational registries. In addition, all issues relevant to the practical
      clinical management of oral anticoagulation with the new direct inhibitors have
      been considered. Specific clinical pathways for optimal use of oral
      anticoagulation with the new directly acting agents are also developed and
      proposed for clinical implementation. Special attention is finally paid to the
      development of clinical algorithms for medium and long-term follow-up of patients
      treated with new oral direct anticoagulants.

PMID- 28751837
TI  - ANMCO/SIC Consensus Document: cardiology networks for outpatient heart failure
      care.
AB  - Changing demographics and an increasing burden of multiple chronic comorbidities
      in Western countries dictate refocusing of heart failure (HF) services from acute
      in-hospital care to better support the long inter-critical out-of- hospital
      phases of HF. In Italy, as well as in other countries, needs of the HF population
      are not adequately addressed by current HF outpatient services, as documented by
      differences in age, gender, comorbidities and recommended therapies between
      patients discharged for acute hospitalized HF and those followed-up at HF
      clinics. The Italian Working Group on Heart Failure has drafted a guidance
      document for the organisation of a national HF care network. Aims of the document
      are to describe tasks and requirements of the different health system points of
      contact for HF patients, and to define how diagnosis, management and care
      processes should be documented and shared among health-care professionals. The
      document classifies HF outpatient clinics in three groups: (i) community HF
      clinics, devoted to management of stable patients in strict liaison with primary
      care, periodic re-evaluation of emerging clinical needs and prompt treatment of
      impending destabilizations, (ii) hospital HF clinics, that target both new onset
      and chronic HF patients for diagnostic assessment, treatment planning and early
      post-discharge follow-up. They act as main referral for general internal medicine
      units and community clinics, and (iii) advanced HF clinics, directed at patients
      with severe disease or persistent clinical instability, candidates to advanced
      treatment options such as heart transplant or mechanical circulatory support.
      Those different types of HF clinics are integrated in a dedicated network for
      management of HF patients on a regional basis, according to geographic features.
      By sharing predefined protocols and communication systems, these HF networks
      integrate multi-professional providers to ensure continuity of care and patient
      empowerment. In conclusion, This guidance document details roles and interactions
      of cardiology specialists, so as to best exploit the added value of their input
      in the care of HF patients and is intended to promote a more efficient and
      effective organization of HF services.

PMID- 28751838
TI  - ANMCO/ELAS/SIBioC Consensus Document: biomarkers in heart failure.
AB  - Biomarkers have dramatically impacted the way heart failure (HF) patients are
      evaluated and managed. A biomarker is a characteristic that is objectively
      measured and evaluated as an indicator of normal biological or pathogenic
      processes, or pharmacological responses to a therapeutic intervention.
      Natriuretic peptides [B-type natriuretic peptide (BNP) and N-terminal proBNP] are
      the gold standard biomarkers in determining the diagnosis and prognosis of HF,
      and a natriuretic peptide-guided HF management looks promising. In the last few
      years, an array of additional biomarkers has emerged, each reflecting different
      pathophysiological processes in the development and progression of HF: myocardial
      insult, inflammation, fibrosis, and remodelling, but their role in the clinical
      care of the patient is still partially defined and more studies are needed before
      to be well validated. Moreover, several new biomarkers have the potential to
      identify patients with early renal dysfunction and appear to have promise to help
      the management cardio-renal syndrome. With different biomarkers reflecting HF
      presence, the various pathways involved in its progression, as well as
      identifying unique treatment options for HF management, a closer cardiologist
      laboratory link, with a multi-biomarker approach to the HF patient, is not far
      ahead, allowing the unique opportunity for specifically tailoring care to the
      individual pathological phenotype.

PMID- 28751839
TI  - The future of telemedicine for the management of heart failure patients: a
      Consensus Document of the Italian Association of Hospital Cardiologists
      (A.N.M.C.O), the Italian Society of Cardiology (S.I.C.) and the Italian Society
      for Telemedicine and eHealth (Digital S.I.T.).
AB  - Telemedicine applied to heart failure patients is a tool for recording and
      providing remote transmission, storage and interpretation of cardiovascular
      parameters and/or useful diagnostic images to allow for intensive home monitoring
      of patients with advanced heart failure, or during the vulnerable post-acute
      phase, to improve patient's prognosis and quality of life. Recently, several meta
      analyses have shown that telemedicine-supported care pathways are not only
      effective but also economically advantageous. Benefits seem to be substantial,
      with a 30-35% reduction in mortality and 15-20% decrease in hospitalizations.
      Patients implanted with cardiac devices can also benefit from an integrated
      remote clinical management since all modern devices can transmit technical and
      diagnostic data. However, telemedicine may provide benefits to heart failure
      patients only as part of a shared and integrated multi-disciplinary and multi
      professional 'chronic care model'. Moreover, the future development of remote
      telemonitoring programs in Italy will require the primary use of products
      certified as medical devices, validated organizational solutions as well as
      legislative and administrative adoption of new care methods and the widespread
      growth of clinical care competence to remotely manage the complexity of
      chronicity. Through this consensus document, Italian Cardiology reaffirms its
      willingness to contribute promoting a new phase of qualitative assessment,
      standardization of processes and testing of telemedicine-based care models in
      heart failure. By recognizing the relevance of telemedicine for the care of non
      hospitalized patients with heart failure, its strategic importance for the design
      of innovative models of care, and the many challenges and opportunities it
      raises, ANMCO and SIC through this document report a consensus on the main
      directions for its widespread and sustainable clinical implementation.

PMID- 28751840
TI  - Clinical pathways and management of antithrombotic therapy in patients with acute
      coronary syndrome (ACS): a Consensus Document from the Italian Association of
      Hospital Cardiologists (ANMCO), Italian Society of Cardiology (SIC), Italian
      Society of Emergency Medicine (SIMEU) and Italian Society of Interventional
      Cardiology (SICI-GISE).
AB  - Antiplatelet therapy is the cornerstone of the pharmacologic management of
      patients with acute coronary syndrome (ACS). Over the last years, several studies
      have evaluated old and new oral or intravenous antiplatelet agents in ACS
      patients. In particular, research was focused on assessing superiority of two
      novel platelet ADP P2Y12 receptor antagonists (i.e., prasugrel and ticagrelor)
      over clopidogrel. Several large randomized controlled trials have been undertaken
      in this setting and a wide variety of prespecified and post-hoc analyses are
      available that evaluated the potential benefits of novel antiplatelet therapies
      in different subsets of patients with ACS. The aim of this document is to review
      recent data on the use of current antiplatelet agents for in-hospital treatment
      of ACS patients. In addition, in order to overcome increasing clinical challenges
      and implement effective therapeutic interventions, this document identifies all
      potential specific care pathway for ACS patients and accordingly proposes
      individualized therapeutic options.

PMID- 28751841
TI  - Consensus Document of the Italian Association of Hospital Cardiologists (ANMCO),
      Italian Society of Cardiology (SIC), Italian Association of Interventional
      Cardiology (SICI-GISE) and Italian Society of Cardiac Surgery (SICCH): clinical
      approach to pharmacologic pre-treatment for patients undergoing myocardial
      revascularization procedures.
AB  - The wide availability of effective drugs in reducing cardiovascular events
      together with the use of myocardial revascularization has greatly improved the
      prognosis of patients with coronary artery disease. The combination of
      antithrombotic drugs to be administered before the knowledge of the coronary
      anatomy and before the consequent therapeutic strategies, can allow to anticipate
      optimal treatment, but can also expose the patients at risk of bleeding that,
      especially in acute coronary syndromes, can significantly weigh on their
      prognosis, even more than the expected theoretical benefit. In non ST-elevation
      acute coronary syndromes patients in particular, we propose a 'selective pre
      treatment' with P2Y12 inhibitors, based on the ischaemic risk, on the bleeding
      risk and on the time scheduled for the execution of coronary angiography. Much of
      the problems concerning this issue would be resolved by an early access to
      coronary angiography, particularly for patients at higher ischaemic and bleeding
      risk.

PMID- 28751842
TI  - ANMCO/AIIC/SIT Consensus Information Document: definition, precision, and
      suitability of electrocardiographic signals of electrocardiographs, ergometry,
      Holter electrocardiogram, telemetry, and bedside monitoring systems.
AB  - The electrocardiogram (ECG) signal can be derived from different sources. These
      include systems for surface ECG, Holter monitoring, ergometric stress tests, and
      telemetry systems and bedside monitoring of vital parameters, which are useful
      for rhythm and ST-segment analysis and ECG screening of electrical sudden cardiac
      death predictors. A precise ECG diagnosis is based upon correct recording,
      elaboration, and presentation of the signal. Several sources of artefacts and
      potential external causes may influence the quality of the original ECG
      waveforms. Other factors that may affect the quality of the information presented
      depend upon the technical solutions employed to improve the signal. The choice of
      the instrumentations and solutions used to offer a high-quality ECG signal are,
      therefore, of paramount importance. Some requirements are reported in detail in
      scientific statements and recommendations. The aim of this consensus document is
      to give scientific reference for the choice of systems able to offer high quality
      ECG signal acquisition, processing, and presentation suitable for clinical use.

PMID- 28751843
TI  - ANMCO-SIMEU Consensus Document: in-hospital management of patients presenting
      with chest pain.
AB  - Chest pain is a common general practice presentation that requires careful
      diagnostic assessment because of its diverse and potentially serious causes.
      However, the evaluation of acute chest pain remains challenging, despite many new
      insights over the past two decades. The percentage of patients presenting to the
      emergency departments because of acute chest pain appears to be increasing.
      Nowadays, there are two essential chest pain-related issues: (i) the missed
      diagnoses of acute coronary syndromes with a poor short-term prognosis; and (ii)
      the increasing percentage of hospitalizations of low-risk cases. It is well known
      that hospitalization of a low-risk chest pain patient can lead to unnecessary
      tests and procedures, with an increasing trend of complications and burden of
      costs. Therefore, the significantly reduced financial resources of healthcare
      systems induce physicians and administrators to improve the efficiency of care
      protocols for patients with acute chest pain. Despite the efforts of the
      Scientific Societies in producing statements on this topic, in Italy there is
      still a significant difference between emergency physicians and cardiologists in
      managing patients with chest pain. For this reason, the aim of the present
      consensus document is double: first, to review the evidence-based efficacy and
      utility of various diagnostic tools, and, second, to delineate the critical
      pathways (describing key steps) that need to be implemented in order to
      standardize the management of chest pain patients, making a correct diagnosis and
      treatment as uniform as possible across the entire country.

PMID- 28751844
TI  - ANMCO/SIT Consensus Document: telemedicine for cardiovascular emergency networks.
AB  - Telemedicine has deeply innovated the field of emergency cardiology, particularly
      the treatment of acute myocardial infarction. The ability to record an ECG in the
      early prehospital phase, thus avoiding any delay in diagnosing myocardial
      infarction with direct transfer to the cath-lab for primary angioplasty, has
      proven to significantly reduce treatment times and mortality. This consensus
      document aims to analyse the available evidence and organizational models based
      on a support by telemedicine, focusing on technical requirements, education, and
      legal aspects.

PMID- 28751845
TI  - ANMCO Position Paper: hospital discharge planning: recommendations and standards.
AB  - The hospital discharge is often poorly standardized and affected by discontinuity
      and fragmentation of care, putting patients at high risk of both post-discharge
      adverse events and early readmission. The present ANMCO document reviews the
      modifiable components of the hospital discharge process related to adverse events
      or re-hospitalizations and suggests the optimal methods for redesigning the whole
      discharge process. The key principles for proper hospital discharge or transfer
      of care acknowledge that the hospital discharge: * is not an isolated event, but
      a process that has to be planned as soon as possible after the admission,
      ensuring that the patient and the caregiver understand and contribute to the
      planned decisions, as equal partners; * is facilitated by a comprehensive
      systemic approach that begins with a multidimensional evaluation process; * must
      be organized by an operator who is responsible for the coordination of all phases
      of the hospital patient journey, involving afterward the general practitioner and
      transferring to them the information and responsibility at discharge; * is the
      result of an integrated multidisciplinary team approach; * appropriately uses the
      transitional and intermediate care services; * is carried out in an organized
      system of care and continuum of services; and * programs the passage of
      information to after-discharge services.

PMID- 28751847
TI  - ANMCO Position Paper: the use of non-vitamin K dependent new oral
      anticoagulant(s) in pulmonary embolism therapy and prevention.
AB  - The new oral anticoagulants (NOACs) have radically changed the approach to the
      treatment and prevention of thromboembolic pulmonary embolism. The authors of
      this position paper face, in succession, issues concerning NOACs, including (i)
      their mechanism of action, pharmacodynamics, and pharmacokinetics; (ii) the use
      in the acute phase with the 'double drug single dose' approach or with 'single
      drug double dose'; (iii) the use in the extended phase with demonstrated efficacy
      and with low incidence of bleeding events; (iv) the encouraging use of NOACs in
      particular subgroups of patients such as those with cancer, the ones under- or
      overweight, with renal insufficiency (creatinine clearance > 30 mL/min), the
      elderly (>75 years); (v) they propose a possible laboratory clinical pathway for
      follow-up; and (vi) carry out an examination on the main drug interactions, their
      potential bleeding risk, and the way to deal with some bleeding complications.
      The authors conclude that the use of NOACs both in the acute phase and in the
      extended phase is equally effective to conventional therapy and associated with
      fewer major bleeding events, which make their use in patients at higher risk of
      recurrences safer.

PMID- 28751846
TI  - Consensus Document of the Italian Association of Hospital Cardiologists (ANMCO),
      Italian Society of Pediatric Cardiology (SICP), and Italian Society of
      Gynaecologists and Obstetrics (SIGO): pregnancy and congenital heart diseases.
AB  - The success of cardiac surgery over the past 50 years has increased numbers and
      median age of survivors with congenital heart disease (CHD). Adults now represent
      two-thirds of patients with CHD; in the USA alone the number is estimated to
      exceed 1 million. In this population, many affected women reach reproductive age
      and wish to have children. While in many CHD patients pregnancy can be
      accomplished successfully, some special situations with complex anatomy,
      iatrogenic or residual pathology are associated with an increased risk of severe
      maternal and fetal complications. Pre-conception counselling allows women to come
      to truly informed choices. Risk stratification tools can also help high-risk
      women to eventually renounce to pregnancy and to adopt safe contraception
      options. Once pregnant, women identified as intermediate or high risk should
      receive multidisciplinary care involving a cardiologist, an obstetrician and an
      anesthesiologist with specific expertise in managing this peculiar medical
      challenge. This document is intended to provide cardiologists working in
      hospitals where an Obstetrics and Gynecology Department is available with a
      streamlined and practical tool, useful for them to select the best management
      strategies to deal with a woman affected by CHD who desires to plan pregnancy or
      is already pregnant.

PMID- 28751848
TI  - ANMCO Position Paper: long-term follow-up of patients with pulmonary
      thromboembolism.
AB  - Venous thromboembolism (VTE), including pulmonary embolism and deep venous
      thrombosis, is the third most common cause of cardiovascular death. The
      management of the acute phase of VTE has already been described in several
      guidelines. However, the management of the follow-up (FU) of these patients has
      been poorly defined. This consensus document, created by the Italian
      cardiologists, wants to clarify this issue using the currently available evidence
      in VTE. Clinical and instrumental data acquired during the acute phase of the
      disease are the cornerstone for planning the FU. Acquired or congenital
      thrombophilic disorders could be identified in apparently unprovoked VTE during
      the FU. In other cases, an occult cancer could be discovered after a VTE. The
      main targets of the post-acute management are to prevent recurrence of VTE and to
      identify the patients who can develop a chronic thromboembolic pulmonary
      hypertension. Knowledge of pathophysiology and therapeutic approaches is
      fundamental to decide the most appropriate long-term treatment. Moreover,
      prognostic stratification during the FU should be constantly updated on the basis
      of the new evidence acquired. Currently, the cornerstone of VTE treatment is
      represented by both the oral and the parenteral anticoagulation. Novel oral
      anticoagulants should be an interesting alternative in the long-term treatment.

PMID- 28751849
TI  - ANMCO/AIAC/SICI-GISE/SIC/SICCH Consensus Document: percutaneous occlusion of the
      left atrial appendage in non-valvular atrial fibrillation patients: indications,
      patient selection, staff skills, organisation, and training.
AB  - Atrial fibrillation (AF) is the most common arrhythmia and its prevalence is
      increasing due to the progressive aging of the population. About 20% of strokes
      are attributable to AF and AF patients are at five-fold increased risk of stroke.
      The mainstay of treatment of AF is the prevention of thromboembolic complications
      with oral anticoagulation therapy. Drug treatment for many years has been based
      on the use of vitamin K antagonists, but recently newer and safer molecules have
      been introduced (dabigatran etexilate, rivaroxaban, apixaban, and edoxaban).
      Despite these advances, many patients still do not receive adequate
      anticoagulation therapy because of contraindications (relative and absolute) to
      this treatment. Over the last decade, percutaneous closure of left atrial
      appendage, main site of thrombus formation during AF, proved effective in
      reducing thromboembolic complications, thus offering a valid medical treatment
      especially in patients at increased bleeding risk. The aim of this consensus
      document is to review the main aspects of left atrial appendage occlusion
      (selection and multidisciplinary assessment of patients, currently available
      methods and devices, requirements for centres and operators, associated therapies
      and follow-up modalities) having as a ground the significant evolution of
      techniques and the available relevant clinical data.

PMID- 28751851
TI  - ANMCO/AIOM/AICO Consensus Document on clinical and management pathways of cardio
      oncology: executive summary.
AB  - Cardiovascular disease and cancer are leading causes of death. Both diseases
      share the same risk factors and, having the highest incidence and prevalence in
      the elderly, they often coexist in the same individual. Furthermore, the enhanced
      survival of cancer patients registered in the last decades and linked to early
      diagnosis and improvement of care, not infrequently exposes them to the
      appearance of ominous cardiovascular complications due to the deleterious effects
      of cancer treatment on the heart and circulatory system. The above considerations
      have led to the development of a new branch of clinical cardiology based on the
      principles of multidisciplinary collaboration between cardiologists and
      oncologists: Cardio-oncology, which aims to find solutions to the prevention,
      monitoring, diagnosis and treatment of heart damage induced by cancer care in
      order to pursue, in the individual patient, the best possible care for cancer
      while minimizing the risk of cardiac toxicity. In this consensus document we
      provide practical recommendations on how to assess, monitor, treat and supervise
      the candidate or patient treated with potentially cardiotoxic cancer therapy in
      order to treat cancer and protect the heart at all stages of the oncological
      disease. Cardiovascular diseases and cancer often share the same risk factors and
      can coexist in the same individual. Such possibility is amplified by the
      deleterious effects of cancer treatment on the heart. The above considerations
      have led to the development of a new branch of clinical cardiology, based on
      multidisciplinary collaboration between cardiologist and oncologist: the cardio
      oncology. It aims to prevent, monitor, and treat heart damages induced by cancer
      therapies in order to achieve the most effective cancer treatment, while
      minimizing the risk of cardiac toxicity. In this paper, we provide practical
      recommendations on how to assess, monitor, treat and supervise patients treated
      with potential cardiotoxic cancer therapies.

PMID- 28751850
TI  - ANMCO/SIC/SICI-GISE/SICCH Executive Summary of Consensus Document on Risk
      Stratification in elderly patients with aortic stenosis before surgery or
      transcatheter aortic valve replacement.
AB  - Aortic stenosis is one of the most frequent valvular diseases in developed
      countries, and its impact on public health resources and assistance is
      increasing. A substantial proportion of elderly people with severe aortic
      stenosis is not eligible to surgery because of the advanced age, frailty, and
      multiple co-morbidities. Transcatheter aortic valve implantation (TAVI) enables
      the treatment of very elderly patients at high or prohibitive surgical risk
      considered ineligible for surgery and with an acceptable life expectancy.
      However, a significant percentage of patients die or show no improvement in
      quality of life (QOL) in the follow-up. In the decision-making process, it is
      important to determine: (i) whether and how much frailty of the patient
      influences the risk of procedures; (ii) how the QOL and the individual patient's
      survival are influenced by aortic valve disease or from other associated
      conditions; and (iii) whether a geriatric specialist intervention to evaluate and
      correct frailty or other diseases with their potential or already manifest
      disabilities can improve the outcome of surgery or TAVI. Consequently, in
      addition to risk stratification with conventional tools, a number of factors
      including multi-morbidity, disability, frailty, and cognitive function should be
      considered, in order to assess the expected benefit of both surgery and TAVI. The
      pre-operative optimization through a multidisciplinary approach with a Heart Team
      can counteract the multiple damage (cardiac, neurological, muscular, respiratory,
      and kidney) that can potentially aggravate the reduced physiological reserves
      characteristic of frailty. The systematic application in clinical practice of
      multidimensional assessment instruments of frailty and cognitive function in the
      screening and the adoption of specific care pathways should facilitate this task.

PMID- 28751852
TI  - Electron-Poor, Fluoro-Containing Arylboronic Acids as Efficient Coupling Partners
      for Bis(1,5-cyclooctadiene)nickel(0)/Tricyclohexylphosphine-Catalyzed Cross
      Coupling Reactions of Aryl Arenesulfonates.
AB  - The use of electron-poor, fluoro-containing arylboronic acids as general coupling
      partners for nickel(0) /tricyclohexylphosphine-catalyzed cross-coupling of aryl
      arenesulfonates is described. Electron-poor fluoro-containing arylboronic acids
      were found to react, faster than electron-rich/neutral arylboronic acids, with (4
      methoxyphenyl)(4-methylbenzenesulfonato-kappaO)bis(tricyclohexylphosphine)nickel.
      Bis(1,5-cyclooctadiene)nickel(0)/tricyclohexylphosphine, (4-methoxyphenyl)(4
      methylbenzenesulfonato-kappaO)bis(tricyclohexylpho sphine)nickel and
      bis(tricyclohexylphosphine)nickel (II) bromide were all found to be efficient
      catalysts/catalyst precursors.

PMID- 28751854
TI  - Neurogenic Processes Are Induced by Very Short Periods of Voluntary Wheel-Running
      in Male Mice.
AB  - Even in the adult mammalian brain progenitor cells proliferate and give rise to
      young neurons which integrate into the neuronal network. The dentate gyrus
      possesses such a neurogenic niche reactive to external stimuli like physical
      activity. In most studies mice or rats have been exposed to wheel running for
      periods of several weeks to activate neurogenesis while early neurogenic
      processes induced by very short running periods are less well understood. To
      address this issue, we allowed male C57Bl/6 mice free access to a running wheel
      for 2 or 7 days. We injected bromodeoxyuridine (BrdU) before the last running
      night, respectively, and quantified cell proliferation with immunocytochemistry
      for BrdU and Ki-67. Furthermore, we performed immunocytochemistry for
      doublecortin (DCX) and real-time RT-qPCR for NeuroD1 to characterize and quantify
      changes in neurogenesis on the protein and mRNA level. Real-time RT-qPCR for
      neurogenic niche factors (BDNF, FGF-2, BMP4, Noggin) was used to detect changes
      in the molecular composition of the neurogenic niche. Interestingly, we observed
      that cell proliferation was already affected after 2 days of running showing a
      transient decrease, which was followed by a rebound with increased proliferation
      after 7 days. Neurogenesis was stimulated after 2 days of running, reflected by
      elevated NeuroD1 mRNA levels, and it was significantly increased after 7 days as
      indicated by DCX immunostaining. On the level of niche factors we observed
      changes in expression in favor of neuronal differentiation (increased BDNF mRNA
      expression) and proliferation (decreased BMP4 mRNA expression) already after 2
      days, although increased proliferation is reflected on the cellular level only
      later. In summary, our data show that 2 days of running are sufficient to
      activate neurogenic processes and we hypothesize that a strong pressure toward
      differentiation privileges neurogenesis while proliferation lags behind.

PMID- 28751853
TI  - Tracking and Quantification of Magnetically Labeled Stem Cells using Magnetic
      Resonance Imaging.
AB  - Stem cell based therapies have critical impacts on treatments and cures of
      diseases such as neurodegenerative or cardiovascular disease. In vivo tracking of
      stem cells labeled with magnetic contrast agents is of particular interest and
      importance as it allows for monitoring of the cells' bio-distribution, viability,
      and physiological responses. Herein, recent advances are introduced in tracking
      and quantification of super-paramagnetic iron oxide (SPIO) nanoparticles-labeled
      cells with magnetic resonance imaging, a noninvasive approach that can
      longitudinally monitor transplanted cells. This is followed by recent
      translational research on human stem cells that are dual-labeled with green
      fluorescence protein (GFP) and SPIO nanoparticles, then transplanted and tracked
      in a chicken embryo model. Cell labeling efficiency, viability, and cell
      differentiation are also presented.

PMID- 28751855
TI  - Interactive Effects of Dopamine Baseline Levels and Cycle Phase on Executive
      Functions: The Role of Progesterone.
AB  - Estradiol and progesterone levels vary along the menstrual cycle and have
      multiple neuroactive effects, including on the dopaminergic system. Dopamine
      relates to executive functions in an "inverted U-shaped" manner and its levels
      are increased by estradiol. Accordingly, dopamine dependent changes in executive
      functions along the menstrual cycle have been previously studied in the pre
      ovulatory phase, when estradiol levels peak. Specifically it has been
      demonstrated that working memory is enhanced during the pre-ovulatory phase in
      women with low dopamine baseline levels, but impaired in women with high dopamine
      baseline levels. However, the role of progesterone, which peaks in the luteal
      cycle phase, has not been taken into account previously. Therefore, the main
      goals of the present study were to extend these findings (i) to the luteal cycle
      phase and (ii) to other executive functions. Furthermore, the usefulness of the
      eye blink rate (EBR) as an indicator of dopamine baseline levels in menstrual
      cycle research was explored. 36 naturally cycling women were tested during three
      cycle phases (menses-low sex hormones; pre-ovulatory-high estradiol; luteal-high
      progesterone and estradiol). During each session, women performed a verbal N-back
      task, as measure of working memory, and a single trial version of the Stroop
      task, as measure of response inhibition and cognitive flexibility. Hormone levels
      were assessed from saliva samples and spontaneous eye blink rate was recorded
      during menses. In the N-back task, women were faster during the luteal phase the
      higher their progesterone levels, irrespective of their dopamine baseline levels.
      In the Stroop task, we found a dopamine-cycle interaction, which was also driven
      by the luteal phase and progesterone levels. For women with higher EBR
      performance decreased during the luteal phase, whereas for women with lower EBR
      performance improved during the luteal phase. These findings suggest an important
      role of progesterone in modulating dopamine-cycle interactions. Additionally, we
      identified the eye blink rate as a non-invasive indicator of baseline dopamine
      function in menstrual cycle research.

PMID- 28751856
TI  - Synucleins and Gene Expression: Ramblers in a Crowd or Cops Regulating Traffic?
AB  - Synuclein family consists of three members, alpha, beta, and gamma-synuclein. Due
      to their involvement in human diseases, they have been thoroughly investigated
      for the last 30 years. Since the first synuclein identification and description,
      members of this family are found in all vertebrates. Sequencing of their genes
      indicates high evolutionary conservation suggesting important function(s) of
      these proteins. They are small naturally unfolded proteins prone to aggregate,
      easily change their conformation, and bind to the membranes. The genes for alpha,
      beta, and gamma-synuclein have different chromosomal localization and a well
      preserved general organization composed of five coding exons of similar size.
      Three genes encoding synucleins are present in the majority of vertebrates,
      however, a variable number of synuclein genes are described in fishes of
      different species. An important question concerns their normal function in cells
      and tissues. alpha-Synuclein is implicated in the regulation of synaptic activity
      through regulation of synaptic vesicle release, while the physiological functions
      of two other members of the family is understood less clearly. Here we discuss
      recent results describing their role in the regulation of gene expression.

PMID- 28751857
TI  - The BDNF val-66-met Polymorphism Affects Neuronal Morphology and Synaptic
      Transmission in Cultured Hippocampal Neurons from Rett Syndrome Mice.
AB  - Brain-derived neurotrophic factor (Bdnf) has been implicated in several
      neurological disorders including Rett syndrome (RTT), an X-linked
      neurodevelopmental disorder caused by loss-of-function mutations in the
      transcriptional modulator methyl-CpG-binding protein 2 (MECP2). The human BDNF
      gene has a single nucleotide polymorphism (SNP)-a methionine (met) substitution
      for valine (val) at codon 66-that affects BDNF's trafficking and activity
      dependent release and results in cognitive dysfunction. Humans that are carriers
      of the met-BDNF allele have subclinical memory deficits and reduced hippocampal
      volume and activation. It is still unclear whether this BDNF SNP affects the
      clinical outcome of RTT individuals. To evaluate whether this BDNF SNP
      contributes to RTT pathophysiology, we examined the consequences of expression of
      either val-BDNF or met-BDNF on dendrite and dendritic spine morphology, and
      synaptic function in cultured hippocampal neurons from wildtype (WT) and Mecp2
      knockout (KO) mice. Our findings revealed that met-BDNF does not increase
      dendritic growth and branching, dendritic spine density and individual spine
      volume, and the number of excitatory synapses in WT neurons, as val-BDNF does.
      Furthermore, met-BDNF reduces dendritic complexity, dendritic spine volume and
      quantal excitatory synaptic transmission in Mecp2 KO neurons. These results
      suggest that the val-BDNF variant contributes to RTT pathophysiology, and that
      BDNF-based therapies should take into consideration the BDNF genotype of the RTT
      individuals.

PMID- 28751858
TI  - Distinct Localization of SNAP47 Protein in GABAergic and Glutamatergic Neurons in
      the Mouse and the Rat Hippocampus.
AB  - Synaptosomal-associated protein of 47 kDa (SNAP47) isoform is an atypical member
      of the SNAP family, which does not contribute directly to exocytosis and synaptic
      vesicle (SV) recycling. Initial characterization of SNAP47 revealed a widespread
      expression in nervous tissue, but little is known about its cellular and
      subcellular localization in hippocampal neurons. Therefore, in the present study
      we applied multiple-immunofluorescence labeling, immuno-electron microscopy and
      in situ hybridization (ISH) and analyzed the localization of SNAP47 in pre- and
      postsynaptic compartments of glutamatergic and GABAergic neurons in the mouse and
      rat hippocampus. While the immunofluorescence signal for SNAP47 showed a
      widespread distribution in both mouse and rat, the labeling pattern was
      complementary in the two species: in the mouse the immunolabeling was higher over
      the CA3 stratum radiatum, oriens and cell body layer. In contrast, in the rat the
      labeling was stronger over the CA1 neuropil and in the CA3 stratum lucidum.
      Furthermore, in the mouse high somatic labeling for SNAP47 was observed in
      GABAergic interneurons (INs). On the contrary, in the rat, while most INs were
      positive, they blended in with the high neuropil labeling. ISH confirmed the high
      expression of SNAP47 RNA in INs in the mouse. Co-staining for SNAP47 and pre- and
      postsynaptic markers in the rat revealed a strong co-localization
      postsynaptically with PSD95 in dendritic spines of pyramidal cells and, to a
      lesser extent, presynaptically, with ZnT3 and vesicular glutamate transporter 1
      (VGLUT1) in glutamatergic terminals such as mossy fiber (MF) boutons.
      Ultrastructural analysis confirmed the pre- and postsynaptic localization at
      glutamatergic synapses. Furthermore, in the mouse hippocampus SNAP47 was found to
      be localized at low levels to dendritic shafts and axon terminals of putative INs
      forming symmetric synapses, indicating that this protein could be trafficked to
      both post- and presynaptic sites in both major cell types. These results reveal
      divergent localization of SNAP47 protein in mouse and rat hippocampus indicating
      species- and cell type-specific differences. SNAP47 is likely to be involved in
      unique fusion machinery which is distinct from the one involved in presynaptic
      neurotransmitter release. Nonetheless, our data suggest that SNAP47 may be
      involved not only postsynaptic, but also in presynaptic function.

PMID- 28751859
TI  - Probabilistic White Matter Atlases of Human Auditory, Basal Ganglia, Language,
      Precuneus, Sensorimotor, Visual and Visuospatial Networks.
AB  - Background: Despite the popularity of functional connectivity analyses and the
      well-known topology of several intrinsic cortical networks, relatively little is
      known about the white matter regions (i.e., structural connectivity) underlying
      these networks. In the current study, we have therefore performed fMRI-guided
      diffusion tensor imaging (DTI) tractography to create probabilistic white matter
      atlases for eight previously identified functional brain networks, including the
      Auditory, Basal Ganglia, Language, Precuneus, Sensorimotor, Primary Visual,
      Higher Visual and Visuospatial Networks. Methods: Whole-brain diffusion imaging
      data were acquired from a cohort of 32 healthy volunteers, and were warped to the
      ICBM template using a two-stage, high-dimensional, non-linear spatial
      normalization procedure. Deterministic tractography, with fractional anisotropy
      (FA) >=0.15 and deviation angle <50 degrees , was then performed using the Fiber
      Association by Continuous Tracking (FACT) algorithm, and a multi-ROI approach to
      identify tracts of interest. Regions-of-interest (ROIs) for each of the eight
      networks were taken from a pre-existing atlas of functionally defined regions to
      explore all ROI-to-ROI connections within each network, and all resulting
      streamlines were saved as binary masks to create probabilistic atlases (across
      participants) for tracts between each ROI-to-ROI pair. Results: The resulting
      functionally-defined white matter atlases (i.e., for each tract and each network
      as a whole) were saved as NIFTI images in stereotaxic ICBM coordinates, and have
      been added to the UManitoba-JHU Functionally-Defined Human White Matter Atlas
      (http://www.nitrc.org/projects/uofm_jhu_atlas/). Conclusion: To the best of our
      knowledge, this work represents the first attempt to comprehensively identify and
      map white matter connectomes for the Auditory, Basal Ganglia, Language,
      Precuneus, Sensorimotor, Primary Visual, Higher Visual and Visuospatial Networks.
      Therefore, the resulting probabilistic atlases represent a unique tool for future
      neuroimaging studies wishing to ascribe voxel-wise or ROI-based changes (i.e., in
      DTI or other quantitative white matter imaging signals) to these functional brain
      networks.

PMID- 28751860
TI  - Pseudo-Bootstrap Network Analysis-an Application in Functional Connectivity
      Fingerprinting.
AB  - Brain parcellation divides the brain's spatial domain into small regions, which
      are represented by nodes within the network analysis framework. While template
      based parcellations are widely used, the parcels on the template do not
      necessarily match individual's functional nodes. A new method is developed to
      overcome the inconsistent network analysis results by by-passing the difficulties
      of parcellating the brain into functionally meaningful areas. First, roughly
      equal-sized parcellations are obtained. Second, these random parcellations are
      applied to individual subjects multiple times and a pseudo-bootstrap (PBS) of the
      network is obtained for statistical inferences. It was found that the variation
      of mean global network metrics from PBS sampling is smaller compared with inter
      subject variation or within-subject variation between two diffusion MRI scans.
      Using the mean global network metrics from PBS sampling, the intra-class
      correlation is always higher than the average obtained from using a single random
      parcellation. As one application, the PBS method was tested on the Human
      Connectome Project resting state dataset to identify individuals across scan
      sessions based on the mean functional connectivity (FC)-a trivial network
      property that has little information about the connectivity between nodes. An
      accuracy rate of ~90% was achieved by simply finding the maximum correlation of
      mean FC of PBS samples between two scan sessions.

PMID- 28751861
TI  - Dementia in Latin America: Epidemiological Evidence and Implications for Public
      Policy.
AB  - Population aging is among the most important global transformations. Today, 12%
      of the world population is of age 60 and over and by the middle of this century
      this segment will represent 21.5%. The increase in population of those aged 80
      and over, also referred to as the "oldest old" or the "very elderly", will be
      even more pronounced, going from 1.7% of the population to 4.5% within the same
      period. Compared to European and North American countries, Latin America (LA) is
      experiencing this unprecedented demographic change at a significantly faster
      rate. Due to demographic and health transitions, the number of people with
      dementia will rise from 7.8 million in 2013 to over 27 million by 2050. Nowadays,
      the global prevalence of dementia in LA has reached 7.1%, with Alzheimer's
      Disease (AD) being the most frequent type. This level is similar to those found
      in developed countries; however, the dementia rate is twice as high as that of
      the 65-69 years age group in developed countries. In addition, the prevalence and
      incidence of dementia is higher among illiterate people. Mortality rates due to
      dementia have risen considerably. The burden and costs of the disease are high
      and must be covered by patients' families. The prevention of dementia and the
      development of long-term care policies and plans for people with dementia in LA,
      which take into account regional differences and similarities, should be urgent
      priorities.

PMID- 28751862
TI  - UTP - Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human
      Enterochromaffin Cells.
AB  - Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to
      trigger or modulate gut neural reflexes and transmit information about
      visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute
      to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms
      modulating Ca2+-dependent 5-HT release are not understood. Previous studies
      indicated that purinergic signaling via ATP and ADP is an important mechanism in
      modulation of 5-HT release. However, EC cells also respond to UTP and UDP
      suggesting uridine triphosphate receptor and signaling pathways are involved as
      well. We tested the hypothesis that UTP is a regulator of 5-HT release in human
      EC cells. Methods: UTP signaling mechanisms were studied in BON cells, a human EC
      model, using Fluo-4/Ca2+imaging, patch-clamp, pharmacological analysis,
      immunohistochemistry, western blots and qPCR. 5-HT release was monitored in BON
      or EC isolated from human gut surgical specimens (hEC). Results: UTP, UTPgammaS,
      UDP or ATP induced Ca2+oscillations in BON. UTP evoked a biphasic concentration
      dependent Ca2+response. Cells responded in the order of UTP, ATP > UTPgammaS >
      UDP >> MRS2768, BzATP, alpha,beta-MeATP > MRS2365, MRS2690, and NF546. Different
      proportions of cells activated by UTP and ATP also responded to UTPgammaS (P2Y4,
      50% cells), UDP (P2Y6, 30%), UTPgammaS and UDP (14%) or MRS2768 (<3%). UTP
      Ca2+responses were blocked with inhibitors of PLC, IP3R, SERCA Ca2+pump,
      La3+sensitive Ca2+channels or chelation of intracellular free Ca2+ by BAPTA/AM.
      Inhibitors of L-type, TRPC, ryanodine-Ca2+pools, PI3-Kinase, PKC or SRC-Kinase
      had no effect. UTP stimulated voltage-sensitive Ca2+currents (ICa), Vm
      depolarization and inhibited IK (not IA) currents. An IKv7.2/7.3 K+ channel
      blocker XE-991 mimicked UTP-induced Vm-depolarization and blocked UTP-responses.
      XE-991 blocked IK and UTP caused further reduction. La3+ or PLC inhibitors
      blocked UTP depolarization; PKC inhibitors, thapsigargin or zero Ca2+buffer did
      not. UTP stimulated 5-HT release in hEC expressing TPH1, 5-HT, P2Y4/P2Y6R. Zero
      Ca2+buffer augmented Ca2+responses and 5-HT release. Conclusion: UTP activates a
      predominant P2Y4R pathway to trigger Ca2+oscillations via internal
      Ca2+mobilization through a PLC/IP3/IP3R/SERCA Ca2+signaling pathway to stimulate
      5-HT release; Ca2+influx is inhibitory. UTP-induced Vm-depolarization depends on
      PLC signaling and an unidentified K channel (which appears independent of
      Ca2+oscillations or Ica/VOCC). UTP-gated signaling pathways triggered by
      activation of P2Y4R stimulate 5-HT release.

PMID- 28751863
TI  - Bone Morphogenetic Protein 9 Protects against Neonatal Hyperoxia-Induced
      Impairment of Alveolarization and Pulmonary Inflammation.
AB  - Aim: Effective treatment of premature infants with bronchopulmonary dysplasia
      (BPD) is lacking. We hypothesize that bone morphogenetic protein 9 (BMP9), a
      ligand of the TGF-beta family that binds to the activin receptor-like kinase 1
      (ALK1)-BMP receptor type 2 (BMPR2) receptor complex, may be a novel therapeutic
      option for BPD. Therefore, we investigated the cardiopulmonary effects of BMP9 in
      neonatal Wistar rats with hyperoxia-induced BPD. Methods: Directly after birth
      Wistar rat pups were exposed to 100% oxygen for 10 days. From day 2 rat pups
      received BMP9 (2.5 MUg/kg, twice a day) or 0.9% NaCl by subcutaneous injection.
      Beneficial effects of BMP9 on aberrant alveolar development, lung inflammation
      and fibrosis, and right ventricular hypertrophy (RVH) were investigated by
      morphometric analysis and cytokine production. In addition, differential mRNA
      expression of BMP9 and its receptor complex: ALK1, BMPR2, and Endoglin, and of
      the ALK1 downstream target transmembrane protein 100 (TMEM100) were studied
      during the development of experimental BPD. Expression of the BMP9 receptor
      complex and TMEM100 was studied in human endothelial and epithelial cell cultures
      and the effect of BMP9 on inflammatory cytokine production and TMEM100 expression
      was studied in endothelial cell cultures. Results:ALK1, ALK2, BMPRII, TMEM100,
      and Endoglin were differentially expressed in experimental BPD, suggesting a role
      for BMP9-dependent signaling in the development of (experimental) BPD. TMEM100
      was expressed in the wall of blood vessels, showing an elastin-like expression
      pattern in arterioles. Expression of TMEM100 mRNA and protein was decreased after
      exposure to hyperoxia. BMP9 treatment of rat pups with hyperoxia-induced
      experimental BPD reduced alveolar enlargement, lung septal thickness and
      fibrosis, and prevented inflammation, but did not attenuate vascular remodeling
      and RVH. The anti-inflammatory effect of BMP9 was confirmed in vitro. Highest
      expression of ALK1, BMPR2, and TMEM100 was observed in human endothelial cell
      cultures. Stimulation of human endothelial cell cultures with BMP9 reduced their
      pro-inflammatory cytokine response and induced TMEM100 expression in pulmonary
      arterial endothelial cells. Conclusion: BMP9 protects against neonatal hyperoxia
      induced BPD by improving aberrant alveolar development, inflammation and
      fibrosis, demonstrating its therapeutic potential for premature infants with
      severe BPD.

PMID- 28751865
TI  - Breakdown of Modularity in Complex Networks.
AB  - The presence of modular organization is a common property of a wide range of
      complex systems, from cellular or brain networks to technological graphs.
      Modularity allows some degree of segregation between different parts of the
      network and has been suggested to be a prerequisite for the evolvability of
      biological systems. In technology, modularity defines a clear division of tasks
      and it is an explicit design target. However, many natural and artificial systems
      experience a breakdown in their modular pattern of connections, which has been
      associated with failures in hub nodes or the activation of global stress
      responses. In spite of its importance, no general theory of the breakdown of
      modularity and its implications has been advanced yet. Here we propose a new,
      simple model of network landscape where it is possible to exhaustively
      characterize the breakdown of modularity in a well-defined way. Specifically, by
      considering the space of minimal Boolean feed-forward networks implementing the
      256 Boolean functions with 3 inputs, we were able to relate functional
      characteristics with the breakdown of modularity. We found that evolution cannot
      reach maximally modular networks under the presence of functional and cost
      constraints, implying the breakdown of modularity is an adaptive feature.

PMID- 28751864
TI  - Exosomes: A Rising Star in Falling Hearts.
AB  - Although exosomes were previously recognized as a mechanism for discharging
      useless cellular components, growing evidence has elucidated their roles in
      conveying information between cells. They contribute to cell-cell communication
      by carrying nucleic acids, proteins and lipids that can, in turn, regulate
      behavior of the target cells. Recent research suggested that exosomes extensively
      participate in progression of diverse cardiovascular diseases (CVDs), such as
      myocardial infarction, cardiomyopathy, pulmonary arterial hypertension and
      others. Here, we summarize effects of exosome-derived molecules (mainly microRNAs
      and proteins) on cardiac function, to examine their potential applications as
      biomarkers or therapeutics in CVDs.

PMID- 28751866
TI  - Ventilatory Efficiency in Children and Adolescents Born Extremely Preterm.
AB  - Purpose: Children and adolescents born extremely preterm (EP) have lower dynamic
      lung volumes and gas transfer capacity than subjects born at term. Most studies
      also report lower aerobic capacity. We hypothesized that ventilatory efficiency
      was poorer and that breathing patterns differed in EP-born compared to term-born
      individuals. Methods: Two area-based cohorts of participants born with
      gestational age <=28 weeks or birth weight <=1000 g in 1982-85 (n = 46) and 1991
      92 (n = 35) were compared with individually matched controls born at term. Mean
      ages were 18 and 10 years, respectively. The participants performed an
      incremental treadmill exercise test to peak oxygen uptake with data averaged over
      20 s intervals. For each participant, the relationship between exhaled minute
      ventilation ([Formula: see text]E) and carbon dioxide output ([Formula: see
      text]CO2) was described by a linear model, and the relationship between tidal
      volume (VT) and [Formula: see text]E by a quadratic model. Multivariate
      regression analyses were done with curve parameters as dependent variables, and
      the categories EP vs. term-born, sex, age, height, weight and forced expiratory
      volume in 1 s (FEV1) as independent variables. Results: In adjusted analyses, the
      slope of the [Formula: see text]E-[Formula: see text]CO2 relationship was
      significantly steeper in the EP than the term-born group, whereas no group
      difference was observed for the breathing pattern, which was related to FEV1
      only. Conclusion: EP-born participants breathed with higher [Formula: see text]E
      for any given CO2 output, indicating lower ventilatory efficiency, possibly
      contributing to lower aerobic capacity. The breathing patterns did not differ
      between the EP and term-born groups when adjusted for FEV1.

PMID- 28751867
TI  - Defects in Vascular Mechanics Due to Aging in Rats: Studies on Arterial Wave
      Properties from a Single Aortic Pressure Pulse.
AB  - Changes in vascular mechanics due to aging include elevated vascular impedance,
      diminished aorta distensibility, and an accelerated return of pulse wave
      reflection, which may increase the systolic workload on the heart. Classically,
      the accurate measurement of vascular mechanics requires the simultaneous
      recording of aortic pressure and flow signals. In practice, it is feasible to
      estimate arterial wave properties in terms of wave transit time (tauw) and wave
      reflection index (RI) by using aortic pressure signal alone. In this study, we
      determined the tau w and magnitudes of the forward (?Pf ?) and backward (?Pb ?)
      pressure waves in Long-Evans male rats aged 4 (n = 14), 6 (n = 17), 12 (n = 17),
      and 18 (n = 24) months, based on the measured aortic pressure and an assumed
      triangular flow (Qtri). The pulsatile pressure wave was the only signal recorded
      in the ascending aorta by using a high-fidelity pressure sensor. The base of the
      unknown Qtri was constructed using a duration, which equals to the ejection time.
      The timing at the peak of the triangle was derived using the fourth-order
      derivative of the aortic pressure waveform. In the 18-month-old rats, the ratio
      of tau w to left ventricular ejection time (LVET) decreased, indicating a decline
      in the distensibility of the aorta. The increased ?Pb ? associated with unaltered
      ?Pf ? enhanced the RI in the older rats. The augmentation index (AI) also
      increased significantly with age. A significant negative correlation between the
      AI and tau w /LVET was observed: AI = -0.7424 - 0.9026 * (tau w /LVET) (r =
      0.4901; P < 0.0001). By contrast, RI was positively linearly correlated with the
      AI as follows: AI = -0.4844 + 2.3634 * RI (r = 0.8423; P < 0.0001). Both the
      decreased tau w /LVET and increased RI suggested that the aging process may
      increase the AI, thereby increasing the systolic hydraulic load on the heart. The
      novelty of the study is that Qtri is constructed using the measured aortic
      pressure wave to approximate its corresponding flow signal, and that calibration
      of Qtri is not essential in the analysis.

PMID- 28751868
TI  - Editorial: Autism Spectrum Disorders: Developmental Trajectories, Neurobiological
      Basis, Treatment Update.

PMID- 28751869
TI  - Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity
      Disorder.
AB  - Growth factors (GFs) are cytokines that regulate the neural development. Recent
      evidence indicates that alterations in the expression level of GFs during
      embryogenesis are linked to the pathophysiology and clinical manifestations of
      attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders
      (ASD). In this concise review, we summarize the current evidence that supports
      the role of brain-derived neurotrophic factor, insulin-like growth factor 2,
      hepatocyte growth factor (HGF), glial-derived neurotrophic factor, nerve growth
      factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of
      ADHD and ASD. We also highlight the potential use of these GFs as clinical
      markers for diagnosis and prognosis of these neurodevelopmental disorders.

PMID- 28751870
TI  - Adaptation to Skew Distortions of Natural Scenes and Retinal Specificity of Its
      Aftereffects.
AB  - Image skew is one of the prominent distortions that exist in optical elements,
      such as in spectacle lenses. The present study evaluates adaptation to image skew
      in dynamic natural images. Moreover, the cortical levels involved in skew coding
      were probed using retinal specificity of skew adaptation aftereffects. Left and
      right skewed natural image sequences were shown to observers as adapting stimuli.
      The point of subjective equality (PSE), i.e., the skew amplitude in simple
      geometrical patterns that is perceived to be unskewed, was used to quantify the
      aftereffect of each adapting skew direction. The PSE, in a two-alternative forced
      choice paradigm, shifted toward the adapting skew direction. Moreover,
      significant adaptation aftereffects were obtained not only at adapted, but also
      at non-adapted retinal locations during fixation. Skew adaptation information was
      transferred partially to non-adapted retinal locations. Thus, adaptation to
      skewed natural scenes induces coordinated plasticity in lower and higher cortical
      areas of the visual pathway.

PMID- 28751871
TI  - Vocabulary Knowledge Predicts Lexical Processing: Evidence from a Group of
      Participants with Diverse Educational Backgrounds.
AB  - Vocabulary knowledge is central to a speaker's command of their language. In
      previous research, greater vocabulary knowledge has been associated with
      advantages in language processing. In this study, we examined the relationship
      between individual differences in vocabulary and language processing performance
      more closely by (i) using a battery of vocabulary tests instead of just one test,
      and (ii) testing not only university students (Experiment 1) but young adults
      from a broader range of educational backgrounds (Experiment 2). Five vocabulary
      tests were developed, including multiple-choice and open antonym and synonym
      tests and a definition test, and administered together with two established
      measures of vocabulary. Language processing performance was measured using a
      lexical decision task. In Experiment 1, vocabulary and word frequency were found
      to predict word recognition speed while we did not observe an interaction between
      the effects. In Experiment 2, word recognition performance was predicted by word
      frequency and the interaction between word frequency and vocabulary, with high
      vocabulary individuals showing smaller frequency effects. While overall the
      individual vocabulary tests were correlated and showed similar relationships with
      language processing as compared to a composite measure of all tests, they
      appeared to share less variance in Experiment 2 than in Experiment 1.
      Implications of our findings concerning the assessment of vocabulary size in
      individual differences studies and the investigation of individuals from more
      varied backgrounds are discussed.

PMID- 28751872
TI  - Editorial: Mental State Understanding: Individual Differences in Typical and
      Atypical Development.

PMID- 28751873
TI  - Targeting Next Generations to Change the Common Practice of Underpowered
      Research.

PMID- 28751874
TI  - CanDiD: A Framework for Linking Executive Function and Education.
AB  - The close association between executive functions (EFs) and educational
      achievement has led to the idea that targeted EF training might facilitate
      learning and goal-directed behavior in the classroom. The evidence that training
      interventions have long-lasting and transferable effects is however decidedly
      mixed (Melby-Lervag and Hulme, 2013; Simons et al., 2016). The goal of the
      current paper is to propose a new CanDiD framework for re-thinking EF and its
      links to education. Based on findings from basic EF research, the proposed CanDiD
      framework highlights dynamic and contextual influences on EF and emphasizes the
      importance of development and individual differences for understanding these
      effects. Implications for remedial interventions and curriculum design are
      discussed.

PMID- 28751875
TI  - Evoking and Measuring Identification with Narrative Characters - A Linguistic
      Cues Framework.
AB  - Current research on identification with narrative characters poses two problems.
      First, although identification is seen as a dynamic process of which the
      intensity varies during reading, it is usually measured by means of post-reading
      questionnaires containing self-report items. Second, it is not clear which
      linguistic characteristics evoke identification. The present paper proposes that
      an interdisciplinary framework allows for more precise manipulations and
      measurements of identification, which will ultimately advance our understanding
      of the antecedents and nature of this process. The central hypothesis of our
      Linguistic Cues Framework is that identification with a narrative character is a
      multidimensional experience for which different dimensions are evoked by
      different linguistic cues. The first part of the paper presents a literature
      review on identification, resulting in a renewed conceptualization of
      identification which distinguishes six dimensions: a spatiotemporal, a
      perceptual, a cognitive, a moral, an emotional, and an embodied dimension. The
      second part argues that each of these dimensions is influenced by specific
      linguistic cues which represent various aspects of the narrative character's
      perspective. The proposed relations between linguistic cues and identification
      dimensions are specified in six propositions. The third part discusses what
      psychological and neurocognitive methods enable the measurement of the various
      identification dimensions in order to test the propositions. By establishing
      explicit connections between the linguistic characteristics of narratives and
      readers' physical, psychological, and neurocognitive responses to narratives,
      this paper develops a research agenda for future empirical research on
      identification with narrative characters.

PMID- 28751876
TI  - Dimensions of Emotional Intelligence and Online Gaming Addiction in Adolescence:
      The Indirect Effects of Two Facets of Perceived Stress.
AB  - This study tested a parallel two-mediator model in which the relationship between
      dimensions of emotional intelligence and online gaming addiction are mediated by
      perceived helplessness and perceived self-efficacy, respectively. The sample
      included 931 male adolescents (mean age = 16.18 years, SD = 0.95) from southern
      China. Data on emotional intelligence (four dimensions, including self-management
      of emotion, social skills, empathy and utilization of emotions), perceived stress
      (two facets, including perceived self-efficacy and perceived helplessness) and
      online gaming addiction were collected, and bootstrap methods were used to test
      this parallel two-mediator model. Our findings revealed that perceived self
      efficacy mediated the relationship between three dimensions of emotional
      intelligence (i.e., self-management, social skills, and empathy) and online
      gaming addiction, and perceived helplessness mediated the relationship between
      two dimensions of emotional intelligence (i.e., self-management and emotion
      utilization) and online gaming addiction. These findings underscore the
      importance of separating the four dimensions of emotional intelligence and two
      facets of perceived stress to understand the complex relationship between these
      factors and online gaming addiction.

PMID- 28751877
TI  - Autoimmune Abnormalities of Postpartum Thyroid Diseases.
AB  - The year following parturition is a critical time for the de novo appearance or
      exacerbation of autoimmune diseases, including autoimmune thyroid disease. The
      vast majority of postpartum thyroid disease consists of postpartum thyroiditis
      (PPT) and the minority by Graves' disease and non-autoimmune thyroiditis. PPT has
      a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review
      published in 2012. Several factors confer risk for the development of PPT.
      Typically, the clinical course of PPT is characterized by three phases:
      thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women
      will have permanent hypothyroidism. The best humoral marker for predictivity,
      already during the first trimester of gestation, is considered positivity for
      thyroperoxidase autoantibodies (TPOAb), though only one-third to half of such
      TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium)
      or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a
      recent study on pregnant women with stable dietary habits, we found that the fish
      consumers had lower rates of positivity (and lower serum levels) of both TPOAb
      and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of
      other diseases that can be observed in the postpartum period, either autoimmune
      or non-autoimmune, thyroid or non-thyroid.

PMID- 28751878
TI  - Autoimmune Thyroiditis and Myasthenia Gravis.
AB  - Autoimmune diseases (AIDs) are the result of specific immune responses directed
      against structures of the self. In normal conditions, the molecules recognized as
      "self" are tolerated by immune system, but when the self-tolerance is lost, the
      immune system could react against molecules from the body, causing the loss of
      self-tolerance, and subsequently the onset of AID that differs for organ target
      and etiology. Autoimmune thyroid disease (ATD) is caused by the development of
      autoimmunity against thyroid antigens and comprises Hashimoto's thyroiditis and
      Graves disease. They are frequently associated with other organ or non-organ
      specific AIDs, such as myasthenia gravis (MG). In fact, ATD seems to be the most
      associated pathology to MG. The etiology of both diseases is multifactorial and
      it is due to genetic and environmental factors, and each of them has specific
      characteristics. The two pathologies show many commonalities, such as the organ
      specificity with a clear pathogenic effect of antibodies, the pathological
      mechanisms, such as deregulation of the immune system and the implication of the
      genetic predisposition. They also show some differences, such as the mode of
      action of the antibodies and therapies. In this review that focuses on ATD and
      MG, the common features and the differences between the two diseases are
      discussed.

PMID- 28751879
TI  - Carbon:Nitrogen:Phosphorus Stoichiometry in Fungi: A Meta-Analysis.
AB  - Surveys of carbon:nitrogen:phosphorus ratios are available now for major groups
      of biota and for various aquatic and terrestrial biomes. However, while fungi
      play an important role in nutrient cycling in ecosystems, relatively little is
      known about their C:N:P stoichiometry and how it varies across taxonomic groups,
      functional guilds, and environmental conditions. Here we present the first
      systematic compilation of C:N:P data for fungi including four phyla (Ascomycota,
      Basidiomycota, Glomeromycota, and Zygomycota). The C, N, and P contents (percent
      of dry mass) of fungal biomass varied from 38 to 57%, 0.23 to 15%, and 0.040 to
      5.5%, respectively. Median C:N:P stoichiometry for fungi was 250:16:1 (molar),
      remarkably similar to the canonical Redfield values. However, we found extremely
      broad variation in fungal C:N:P ratios around the central tendencies in C:N:P
      ratios. Lower C:P and N:P ratios were found in Ascomycota fungi than in
      Basidiomycota fungi while significantly lower C:N ratios (p < 0.05) and higher
      N:P ratios (p < 0.01) were found in ectomycorrhizal fungi than in saprotrophs.
      Furthermore, several fungal stoichiometric ratios were strongly correlated with
      geographic and abiotic environmental factors, especially latitude, precipitation,
      and temperature. The results have implications for understanding the roles that
      fungi play in function in symbioses and in soil nutrient cycling. Further work is
      needed on the effects of actual in situ growth conditions of fungal growth on
      stoichiometry in the mycelium.

PMID- 28751880
TI  - Genomic Reconstruction of Carbohydrate Utilization Capacities in Microbial-Mat
      Derived Consortia.
AB  - Two nearly identical unicyanobacterial consortia (UCC) were previously isolated
      from benthic microbial mats that occur in a heliothermal saline lake in northern
      Washington State. Carbohydrates are a primary source of carbon and energy for
      most heterotrophic bacteria. Since CO2 is the only carbon source provided, the
      cyanobacterium must provide a source of carbon to the heterotrophs. Available
      genomic sequences for all members of the UCC provide opportunity to investigate
      the metabolic routes of carbon transfer between autotroph and heterotrophs. Here,
      we applied a subsystem-based comparative genomics approach to reconstruct
      carbohydrate utilization pathways and identify glycohydrolytic enzymes,
      carbohydrate transporters and pathway-specific transcriptional regulators in 17
      heterotrophic members of the UCC. The reconstructed metabolic pathways include
      800 genes, near a one-fourth of which encode enzymes, transporters and regulators
      with newly assigned metabolic functions resulting in discovery of novel
      functional variants of carbohydrate utilization pathways. The in silico analysis
      revealed the utilization capabilities for 40 carbohydrates and their derivatives.
      Two Halomonas species demonstrated the largest number of sugar catabolic
      pathways. Trehalose, sucrose, maltose, glucose, and beta-glucosides are the most
      commonly utilized saccharides in this community. Reconstructed regulons for
      global regulators HexR and CceR include central carbohydrate metabolism genes in
      the members of Gammaproteobacteria and Alphaproteobacteria, respectively.
      Genomics analyses were supplemented by experimental characterization of metabolic
      phenotypes in four isolates derived from the consortia. Measurements of isolate
      growth on the defined medium supplied with individual carbohydrates confirmed
      most of the predicted catabolic phenotypes. Not all consortia members use
      carbohydrates and only a few use complex polysaccharides suggesting a
      hierarchical carbon flow from cyanobacteria to each heterotroph. In summary, the
      genomics-based identification of carbohydrate utilization capabilities provides a
      basis for future experimental studies of carbon flow in UCC.

PMID- 28751881
TI  - Eelgrass Leaf Surface Microbiomes Are Locally Variable and Highly Correlated with
      Epibiotic Eukaryotes.
AB  - Eelgrass (Zostera marina) is a marine foundation species essential for coastal
      ecosystem services around the northern hemisphere. Like all macroscopic
      organisms, it possesses a microbiome (here defined as an associated prokaryotic
      community) which may play critical roles in modulating the interaction of
      eelgrass with its environment. For example, its leaf surface microbiome could
      inhibit or attract eukaryotic epibionts which may overgrow the eelgrass leading
      to reduced primary productivity and subsequent eelgrass meadow decline. We used
      amplicon sequencing of the 16S and 18S rRNA genes of prokaryotes and eukaryotes
      to assess the leaf surface microbiome (prokaryotes) as well as eukaryotic
      epibionts in- and outside lagoons on the German Baltic Sea coast. Prokaryote
      microbiomes varied substantially both between sites inside lagoons and between
      open coastal and lagoon sites. Water depth, leaf area and biofilm chlorophyll a
      concentration explained a large amount of variation in both prokaryotic and
      eukaryotic community composition. The prokaryotic microbiome and eukaryotic
      epibiont communities were highly correlated, and network analysis revealed
      disproportionate co-occurrence between a limited number of eukaryotic taxa and
      several bacterial taxa. This suggests that eelgrass leaf surfaces are home to a
      mosaic of microbiomes of several epibiotic eukaryotes, in addition to the
      microbiome of the eelgrass itself. Our findings thereby underline that eukaryotic
      diversity should be taken into account in order to explain prokaryotic microbiome
      assembly and dynamics in aquatic environments.

PMID- 28751882
TI  - Spatial and Temporal Microbial Patterns in a Tropical Macrotidal Estuary Subject
      to Urbanization.
AB  - Darwin Harbour in northern Australia is an estuary in the wet-dry tropics subject
      to increasing urbanization with localized water quality degradation due to
      increased nutrient loads from urban runoff and treated sewage effluent. Tropical
      estuaries are poorly studied compared to temperate systems and little is known
      about the microbial community-level response to nutrients. We aimed to examine
      the spatial and temporal patterns of the bacterial community and its association
      with abiotic factors. Since Darwin Harbour is macrotidal with strong seasonal
      patterns and mixing, we sought to determine if a human impact signal was
      discernible in the microbiota despite the strong hydrodynamic forces. Adopting a
      single impact-double reference design, we investigated the bacterial community
      using next-generation sequencing of the 16S rRNA gene from water and sediment
      from reference creeks and creeks affected by effluent and urban runoff. Samples
      were collected over two years during neap and spring tides, in the dry and wet
      seasons. Temporal drivers, namely seasons and tides had the strongest
      relationship to the water microbiota, reflecting the macrotidal nature of the
      estuary and its location in the wet-dry tropics. The neap-tide water microbiota
      provided the clearest spatial resolution while the sediment microbiota reflected
      current and past water conditions. Differences in patterns of the microbiota
      between different parts of the harbor reflected the harbor's complex
      hydrodynamics and bathymetry. Despite these variations, a microbial signature was
      discernible relating to specific effluent sources and urban runoff, and the
      composite of nutrient levels accounted for the major part of the explained
      variation in the microbiota followed by salinity. Our results confirm an overall
      good water quality but they also reflect the extent of some hypereutrophic areas.
      Our results show that the microbiota is a sensitive indicator to assess ecosystem
      health even in this dynamic and complex ecosystem.

PMID- 28751883
TI  - Captivity Shapes the Gut Microbiota of Andean Bears: Insights into Health
      Surveillance.
AB  - The Andean bear is an endemic species of the tropical Andes who has an almost
      exclusively plant-based diet. Since herbivorous mammals do not carry enzymes for
      fiber degradation, the establishment of symbiosis with cellulolytic
      microorganisms in their gastrointestinal (GI) tract is necessary to help them
      fulfill their nutritional needs. Furthermore, as described for other mammals, a
      stable, diverse, and balanced gut microbial composition is an indicator of a
      healthy status of the host; under disturbances this balance can be lost, leading
      to potential diseases of the host. The goal of this study was to describe the gut
      microbiota of wild and captive Andean bears and determine how habitat status
      influences the composition and diversity of the gut symbiotic community. Fecal
      samples from wild (n = 28) and captive (n = 8) Andean bears were collected in
      "Reserva Pantano de Martos" and "Fundacion Bioandina", Colombia. Composition and
      diversity analyses were performed using amplicons from the V4 region of the 16S
      rDNA gene sequenced using the Ion PGM platform. PICRUSt algorithm was applied to
      predict the gene content of the gut microbiome of wild and captive Andean bears.
      A total of 5,411 and 838 OTUs were identified for wild and captive bears,
      respectively. Captive bears contained a lower number of bacterial phyla (n = 7)
      compared to wild individuals (n = 9). Proteobacteria (59.03%) and Firmicutes
      (14.03%) were the phyla that contributed the most to differences between wild and
      captive bears (overall dissimilarity = 87.72%). At family level,
      Enterobacteriaceae drove the main differences between the two groups (13.7%).
      PICRUSt metagenomics predictions suggested a similar pattern of relative
      abundance of gene families associated with the metabolism of carbohydrates across
      samples in wild individuals, despite the taxonomic differences of their gut
      microbiota. Captivity alters the availability and diversity of food resources,
      which likely reduces microbiota richness and diversity compared to wild
      individuals. Further considerations should be taken into account for nutritional
      schemes improving ex-situ conservation and its potential as a surveillance tool
      of endangered populations of wild Andean bears.

PMID- 28751884
TI  - Accumulation of Azole Drugs in the Fungal Plant Pathogen Magnaporthe oryzae Is
      the Result of Facilitated Diffusion Influx.
AB  - Magnaporthe oryzae is an agricultural mold that causes disease in rice, resulting
      in devastating crop losses. Since rice is a world-wide staple food crop,
      infection by M. oryzae poses a serious global food security threat. Fungicides,
      including azole antifungals, are used to prevent and combat M. oryzae plant
      infections. The target of azoles is CYP51, an enzyme localized on the endoplasmic
      reticulum (ER) and required for fungal ergosterol biosynthesis. However, many
      basic drug-pathogen interactions, such as how the azole gets past the fungal cell
      wall and plasma membrane, and is transported to the ER, are not understood. In
      addition, reduced intracellular accumulation of antifungals has consistently been
      observed as a drug resistance mechanism in many fungal species. Studying the
      basic biology of drug-pathogen interactions may elucidate uncharacterized
      mechanisms of drug resistance and susceptibility in M. oryzae and potentially
      other related fungal pathogens. We characterized intracellular accumulation of
      azole drugs in M. oryzae using a radioactively labeled fluconazole uptake assay
      to gain insight on whether azoles enter the cell by passive diffusion, active
      transport, or facilitated diffusion. We show that azole accumulation is not ATP
      dependent, nor does it rely on a pH-dependent process. Instead there is evidence
      for azole drug uptake in M. oryzae by a facilitated diffusion mechanism. The
      uptake system is specific for azole or azole-like compounds and can be modulated
      depending on cell phase and growth media. In addition, we found that co-treatment
      of M. oryzae with 'repurposed' clorgyline and radio-labeled fluconazole prevented
      energy-dependent efflux of fluconazole, resulting in an increased intracellular
      concentration of fluconazole in the fungal cell.

PMID- 28751885
TI  - A Multilocus Sequence Analysis Scheme for Phylogeny of Thioclava Bacteria and
      Proposal of Two Novel Species.
AB  - A multilocus sequence analysis (MLSA) was established and performed on the genus
      Thioclava, including 23 strains isolated from diverse marine environments, with
      the aim of better differentiation of strains and species within this genus. The
      study was based on sequences of 16S rRNA gene and five protein-coding
      housekeeping genes, gyrB, rpoD, dnaK, trpB, and recA. In contrast to 16S rRNA
      gene-based tree that was unable to separate some species within this genus, each
      tree based on a single housekeeping gene and MLSA had consistently defined seven
      clades, corresponding to the five established ones and two novel ones. The
      digital DNA-DNA hybridization and average nucleotide identity analyses based on
      genome sequences of the representative strains reconfirmed the validity of the
      MLSA analysis, and recommended a 97.3% MLSA similarity as the soft species
      threshold and nine species representing the five known and four putative novel
      species. Two of the four new species were identified as Thioclava sediminum sp.
      nov. (type strain TAW-CT134T = MCCC 1A10143T = LMG 29615T) and Thioclava marinus
      sp. nov. (type strain 11.10-0-13T = MCCC 1A03502T = LMG 29618T) by using a
      polyphasic taxonomic approach. Taken together, the newly established MLSA in this
      study first described the variability and phylogeny of the genus Thioclava which
      contributes to better understanding its ecology and evolution.

PMID- 28751886
TI  - Salmonella enterica serovar Infantis from Food and Human Infections, Switzerland,
      2010-2015: Poultry-Related Multidrug Resistant Clones and an Emerging ESBL
      Producing Clonal Lineage.
AB  - Objectives: The aim of this study was to characterize a collection of 520
      Salmonella enterica serovar Infantis strains isolated from food (poultry meat),
      human infections and environmental sources from the years 2010, 2013 and 2015 in
      Switzerland. Methods: We performed antimicrobial susceptibility testing and
      pulsed-field gel electrophoresis (PFGE) analysis on all 520 S. Infantis isolates,
      and whole genome sequencing (WGS) on 32 selected isolates. Results: The majority
      (74.8%) of the isolates was multidrug resistant (MDR). PFGE analysis revealed
      that 270 (51.9%) isolates shared an identity of 90%. All isolates subjected to
      WGS belonged to sequence type (ST) 32 or a double-locus variant thereof (one
      isolate). Seven (21.9%) of the sequenced isolates were phylogenetically related
      to the broiler-associated clone B that emerged in Hungary and subsequently spread
      within and outside of Europe. In addition, three isolates harboring blaCTX-M-65
      on a predicted large (~320 kb) plasmid grouped in a distinct cluster. Conclusion:
      This study documents the presence of the Hungarian clone B and related clones in
      food and human isolates between 2010 and 2015, and the emergence of a blaCTX-M-65
      harboring MDR S. serovar Infantis lineage.

PMID- 28751887
TI  - Azorhizobium caulinodans Transmembrane Chemoreceptor TlpA1 Involved in Host
      Colonization and Nodulation on Roots and Stems.
AB  - Azorhizobium caulinodans ORS571 is a motile soil bacterium that interacts
      symbiotically with legume host Sesbania rostrata, forming nitrogen-fixing root
      and stem nodules. Bacterial chemotaxis plays an important role in establishing
      this symbiotic relationship. To determine the contribution of chemotaxis to
      symbiosis in A. caulinodans ORS571-S. rostrata, we characterized the function of
      TlpA1 (transducer-like protein in A. caulinodans), a chemoreceptor predicted by
      SMART (Simple Modular Architecture Research Tool), containing two N-terminal
      transmembrane regions. The tlpA1 gene is located immediately upstream of the
      unique che gene cluster and is transcriptionally co-oriented. We found that a
      DeltatlpA1 mutant is severely impaired for chemotaxis to various organic acids,
      glycerol and proline. Furthermore, biofilm forming ability of the strain carrying
      the mutation is reduced under certain growth conditions. Interestingly,
      competitive colonization ability on S. rostrata root surfaces is impaired in the
      DeltatlpA1 mutant, suggesting that chemotaxis of the A. caulinodans ORS571
      contributes to root colonization. We also found that TlpA1 promotes competitive
      nodulation not only on roots but also on stems of S. rostrata. Taken together,
      our data strongly suggest that TlpA1 is a transmembrane chemoreceptor involved in
      A. caulinodans-S. rostrata symbiosis.

PMID- 28751888
TI  - Identification of the Components Involved in Cyclic Di-AMP Signaling in
      Mycoplasma pneumoniae.
AB  - Bacteria often use cyclic dinucleotides as second messengers for signal
      transduction. While the classical molecule c-di-GMP is involved in lifestyle
      selection, the functions of the more recently discovered signaling nucleotide
      cyclic di-AMP are less defined. For many Gram-positive bacteria, c-di-AMP is
      essential for growth suggesting its involvement in a key cellular function. We
      have analyzed c-di-AMP signaling in the genome-reduced pathogenic bacterium
      Mycoplasma pneumoniae. Our results demonstrate that these bacteria produce c-di
      AMP, and we could identify the diadenylate cyclase CdaM (MPN244). This enzyme is
      the founding member of a novel family of diadenylate cyclases. Of two potential c
      di-AMP degrading phosphodiesterases, only PdeM (MPN549) is active in c-di-AMP
      degradation, whereas NrnA (MPN140) was reported to degrade short
      oligoribonucleotides. As observed in other bacteria, both the c-di-AMP
      synthesizing and the degrading enzymes are essential for M. pneumoniae suggesting
      control of a major homeostatic process. To obtain more insights into the nature
      of this process, we have identified a c-di-AMP-binding protein from M.
      pneumoniae, KtrC. KtrC is the cytoplasmic regulatory subunit of the low affinity
      potassium transporter KtrCD. It is established that binding of c-di-AMP inhibits
      the KtrCD activity resulting in a limitation of potassium uptake. Our results
      suggest that the control of potassium homeostasis is the essential function of c
      di-AMP in M. pneumoniae.

PMID- 28751889
TI  - Morphological and Mitochondrial Genomic Characterization of Eyeworms (Thelazia
      callipaeda) from Clinical Cases in Central China.
AB  - Thelazia callipaeda, also called the oriental eyeworm, is the major etiological
      agent of human thelaziasis. Cases of thelaziasis have increased in recent years
      in China. Although this species is of medical importance, the genetics and
      phylogenetic systematics of T. callipaeda are poorly understood. In this study,
      we first reported three cases of thelaziasis in central China. All clinical
      isolates were identified as T. callipaeda according to morphological
      characteristics by light microscopy and scanning electron microscopy. Next,
      complete mitochondrial (mt) genomes for the three T. callipaeda isolates from
      different geographical locations were fully characterized using an Illumina
      sequencing platform. In addition, all available mt genomes of spirurid nematodes
      in GenBank were included to reconstruct the phylogeny and to explore the
      evolutionary histories of the isolates. The genome features of the T. callipaeda
      isolates contained 12 PCGs, 22 transfer RNA genes, two ribosomal RNA genes and a
      major non-coding region. The mtDNA nucleotide sequences of the T. callipaeda
      isolates from different hosts and different locations were similar. The nad6 gene
      showed high sequence variability among all isolates, which is worth considering
      for future population genetic studies of T. callipaeda. Phylogenetic analyses
      based on maximum parsimony and Bayesian inference methods revealed close
      relationships among Thelaziidae, Onchocercidae, Setariidae, Gongylonematidae,
      Physalopteridae, Dracunculidae, and Philometridae. The monophyly of the T.
      callipaeda isolates from different hosts and distinct geographical locations was
      confirmed. The entire mt genomes of T. callipaeda presented in this study will
      serve as a useful dataset for studying the population genetics and phylogenetic
      relationships of Thelazia species.

PMID- 28751890
TI  - TLR7/TLR9- and B Cell Receptor-Signaling Crosstalk: Promotion of Potentially
      Dangerous B Cells.
AB  - B cells are capable of receptor-mediated responses to foreign antigens.
      Recognition of microbial-derived nucleic acid (NA) by toll-like receptors (TLRs)
      7 and 9 in B cells has been substantiated. Endogenous NA released from damaged or
      dying cells can also be immunogenic in certain contexts and can incite aberrant
      activation of B cells. When TLR-driven B cell receptor (BCR)-activated B cells
      are not properly constrained, pathologic autoantibodies are produced. It is also
      clear that endosomal TLR7/TLR9 can operate in conjunction with BCR. In addition
      to BCR signaling, a balance between TLR7 and TLR9 is pivotal in the development
      of B cell autoreactivity. While TLR9 is important in normal memory B cell
      responses through BCR, TLR9 activation has been implicated in autoantibody
      production. Paradoxically, TLR9 also plays known protective roles against
      autoimmunity by directly and indirectly inhibiting TLR7-mediated autoantibody
      production. Herein, we summarize literature supporting mechanisms underpinning
      the promotion of pathological BCR-activated B cells by TLR7 and TLR9. We focus on
      the literature regarding known points of TLR7/TLR9 and BCR crosstalk. Data also
      suggest that the degree of TLR responsiveness relies on alterations of certain
      intrinsic B-cell signaling molecules and is also context specific. Because
      allogeneic hematopoietic stem cell transplantation is a high NA and B cell
      activating factor environment, we conclude that B cell studies of synergistic TLR
      BCR signaling in human diseases like chronic graft-versus-host disease are
      warranted. Further understanding of the distinct molecular pathways mediating TLR
      BCR synergy will lead to the development of therapeutic strategies in autoimmune
      disease states.

PMID- 28751891
TI  - Deconvolution of the Response to Bacillus Calmette-Guerin Reveals NF-kappaB
      Induced Cytokines As Autocrine Mediators of Innate Immunity.
AB  - Bacillus Calmette-Guerin (BCG) is used as a vaccine and diagnostic test for
      tuberculosis, as well as immunotherapy in the treatment of bladder cancer. While
      clinically useful, the response to mycobacterial stimulation is complex and the
      induced protein signature remains poorly defined. We characterized the cell types
      directly engaged by BCG, as well as the induced cytokine loops that transmit
      signal(s) to bystander cells. Standardized whole-blood stimulations and
      mechanistic studies on single and purified cell populations identified distinct
      patterns of activation in monocytes as compared to neutrophils and invariant
      lymphocyte populations. Deconvoluting the role of Toll-like receptor 2/4 and
      Dectin-1/2 in the inflammatory response to BCG, we revealed Dectin-1/2 as
      dominant in neutrophils as compared to monocytes, which equally engaged both
      pathways. Furthermore, we quantified the role of NF-kappaB and NADPH/reactive
      oxygen species (ROS)-dependent cytokines, which triggered a JAK1/2-dependent
      amplification loop and accounted for 40-50% of the induced response to BCG. In
      sum, this study provides new insight into the molecular and cellular pathways
      involved in the response to BCG, establishing the basis for a new generation of
      immunodiagnostic tools.

PMID- 28751892
TI  - Sharpening the Edge for Precision Cancer Immunotherapy: Targeting Tumor Antigens
      through Oncolytic Vaccines.
AB  - Cancer immunotherapy represents a promising, modern-age option for treatment of
      cancers. Among the many immunotherapies being developed, oncolytic viruses (OVs)
      are slowly moving to the forefront of potential clinical therapeutic agents,
      especially considering the fact that the first oncolytic virus was recently
      approved by the Food and Drug Administration for the treatment of melanoma. OVs
      were originally discovered for their ability to kill cancer cells, but they have
      emerged as unconventional cancer immunotherapeutics due to their ability to
      activate a long-term antitumor immune response. This immune response not only
      eliminates cancer cells but also offers potential for preventing cancer
      recurrence. A fundamental requirement for the generation of such a strong
      antitumor T cell response is the recognition of an immunogenic tumor antigen by
      the antitumor T cell. Several tumor antigens capable of activating these
      antitumor T cells have been identified and are now being expressed through
      genetically engineered OVs to potentiate antitumor immunity. With the emergence
      of novel technologies for identifying tumor antigens and immunogenic epitopes in
      a myriad of cancers, design of "oncolytic vaccines" expressing highly specific
      tumor antigens provides a great strategy for targeting tumors. Here, we highlight
      the various OVs engineered to target tumor antigens and discuss multiple studies
      and strategies used to develop oncolytic vaccine regimens. We also contend how,
      going forward, a combination of technologies for identifying novel immunogenic
      tumor antigens and rational design of oncolytic vaccines will pave the way for
      the next generation of clinically efficacious cancer immunotherapies.

PMID- 28751893
TI  - Patients Lacking a KIR-Ligand of HLA Group C1 or C2 Have a Better Outcome after
      Umbilical Cord Blood Transplantation.
AB  - Donor natural killer (NK) cells can destroy residual leukemic cells after
      allogeneic hematopoietic stem cell transplantation. This effect is based on the
      interaction of killer-cell immunoglobulin-like receptors (KIR) of donor NK cells
      with ligands of the major histocompatibility complex found on the surface of the
      target cells. HLA-C1 subtypes provide the ligand for KIR2DL2 and KIR2DL3 and the
      HLA-C2 subtypes for KIR2DL1. We have studied the probability of relapse (PR)
      after single-unit unrelated cord blood transplantation (UCBT) in relation to the
      potential graft-vs.-leukemia effect mediated by NK cells present in the umbilical
      cord blood (UCB) by analyzing KIR-ligand and HLA-C typing of the receptor. Data
      from 33 consecutive patients given a single unit UCBT were included. We have
      considered two groups of patients based on the absence or the presence of one of
      the C-ligands for inhibitory KIR and the incompatibility HLA-C1/2 between UCB and
      patients. Group 1 (n = 21): the patient lacks a C-ligand for inhibitory KIR
      present in UCB NK cells, i.e., patients homozygous C1/C1 or C2/C2. Group 2 (n =
      12): patients heterozygous C1/C2 in which KIR-mediated graft-vs.-leukemia effect
      is not expected (presence of both C ligands for inhibitory KIR in the receptor).
      With a median follow-up post-UCBT of 93 months, patients with absence of a C
      ligand for inhibitory KIRs (Group 1) showed a lower actuarial PR than patients
      with both C-ligands (group 2): 21 +/- 10 vs. 68 +/- 18% at 2 year and 36 +/- 13
      vs. 84 +/- 14% at 5 years (p = 0.025), respectively. In patients with acute
      lymphoblastic leukemia, the 2-year PR was 36 +/- 21% for group 1 and 66 +/- 26%
      for 2 (p = 0.038). Furthermore, group 1 had a lower incidence of grades II-IV
      acute graft-vs.-host disease (p = 0.04). In the setting of UCBT, the absence of a
      C-ligand (C1 or C2) of inhibitory KIR in the patient is associated with lower PR,
      which is probably due to the graft-vs.-host leukemia effect caused by UCB NK
      cells that lack a ligand for the inhibitory KIR 2DL1/2DL2/2DL3.

PMID- 28751894
TI  - Transient Depletion of CD169+ Cells Contributes to Impaired Early Protection and
      Effector CD8+ T Cell Recruitment against Mucosal Respiratory Syncytial Virus
      Infection.
AB  - Respiratory syncytial virus (RSV) is a major cause of respiratory viral
      infections in infants and children. Alveolar macrophages (AMs) play a crucial
      role in combatting airborne pathogens, strongly express CD169, and are localized
      in the lung alveoli. Therefore, we used CD169-diphtheria toxin receptor (DTR)
      transgenic mice to explore the roles of CD169+ cells in immune responses to
      mucosal RSV infection. The administration of diphtheria toxin to CD169-DTR mice
      induced specific AM depletion and reduced the recruitment of Ly6Chi monocytes.
      Notably, CD169+ cell depletion reduced levels of innate cytokines, such as
      interferon-beta, IL-6, and TNF-alpha, in bronchoalveolar lavage fluid during RSV
      infection without affecting the production of proinflammatory chemokines.
      Moreover, the depletion of CD169+ cells increased the recruitment of inflammatory
      cells to the lung during the early stage of RSV infection, although not during
      the later stages of RSV infection. Furthermore, the depletion of CD169+ cells
      reduced the recruitment of effector CD8+ T cells to the lungs after RSV mucosal
      infection. Our findings suggest that modulating the number of CD169+ cells to
      enhance immune responses to RSV infection may be useful as a new therapeutic
      strategy.

PMID- 28751895
TI  - A Multiple QTL-Seq Strategy Delineates Potential Genomic Loci Governing Flowering
      Time in Chickpea.
AB  - Identification of functionally relevant potential genomic loci using an
      economical, simpler and user-friendly genomics-assisted breeding strategy is
      vital for rapid genetic dissection of complex flowering time quantitative trait
      in chickpea. A high-throughput multiple QTL-seq strategy was employed in two
      inter (Cicer arietinum desi accession ICC 4958 * C reticulatum wild accession ICC
      17160)- and intra (ICC 4958 * C. arietinum kabuli accession ICC 8261)-specific
      RIL mapping populations to identify the major QTL genomic regions governing
      flowering time in chickpea. The whole genome resequencing discovered 1635117 and
      592486 SNPs exhibiting differentiation between early- and late-flowering mapping
      parents and bulks, constituted by pooling the homozygous individuals of extreme
      flowering time phenotypic trait from each of two aforesaid RIL populations. The
      multiple QTL-seq analysis using these mined SNPs in two RIL mapping populations
      narrowed-down two longer (907.1 kb and 1.99 Mb) major flowering time QTL genomic
      regions into the high-resolution shorter (757.7 kb and 1.39 Mb) QTL intervals on
      chickpea chromosome 4. This essentially identified regulatory as well as coding
      (non-synonymous/synonymous) novel SNP allelic variants from two efl1 (early
      flowering 1) and GI (GIGANTEA) genes regulating flowering time in chickpea.
      Interestingly, strong natural allelic diversity reduction (88-91%) of two known
      flowering genes especially mapped at major QTL intervals as compared to that of
      background genomic regions (where no flowering time QTLs were mapped; 61.8%) in
      cultivated vis-a-vis wild Cicer gene pools was evident inferring the significant
      impact of evolutionary bottlenecks on these loci during chickpea domestication.
      Higher association potential of coding non-synonymous and regulatory SNP alleles
      mined from efl1 (36-49%) and GI (33-42%) flowering genes for early and late
      flowering time differentiation among chickpea accessions was evident. The
      robustness and validity of two functional allelic variants-containing genes
      localized at major flowering time QTLs was apparent by their identification from
      multiple intra-/inter-specific mapping populations of chickpea. The functionally
      relevant molecular tags delineated can be of immense use for deciphering the
      natural allelic diversity-based domestication pattern of flowering time and
      expediting genomics-aided crop improvement to develop early flowering cultivars
      of chickpea.

PMID- 28751897
TI  - Comparative Agronomic Performance and Reaction to Fusarium wilt of Lens culinaris
      * L. orientalis and L. culinaris * L. ervoides derivatives.
AB  - The development of transgressive phenotype in the segregating populations has
      been speculated to contribute to niche divergence of hybrid lineages, which
      occurs most frequently at larger genetic distances. Wild Lens species are
      considered to be more resistant against major biotic and abiotic stresses than
      that of the cultivated species. In the present study, we assessed the comparative
      agronomic performance of lentil (Lens culinaris subsp. culinaris) inter-sub
      specific (L. culinaris subsp. orientalis) and interspecific (L. ervoides)
      derivatives, also discussed its probable basis of occurrence. The F3, F4, and F5
      inter sub-specific and interspecific populations of ILL8006 * ILWL62 and ILL10829
      * ILWL30, respectively revealed a substantial range of variation for majority of
      agro-morphological traits as reflected by the range, mean and coefficient of
      variation. A high level of fruitful heterosis was also observed in F3 and F4
      progeny for important traits of interest. Phenotypic coefficient of variation
      (PCV) was higher in magnitude than genotypic coefficient of variation (GCV) in
      all generations for several quantitative characters. The results showed high
      heritability estimates for majority of traits in conjunction with low to high
      genetic advance in F3 and F4 generations. Further, F5 progeny of ILL10829 *
      ILWL30, manifested resistant disease reaction for fifteen recombinant inbred
      lines (RILs) against (Fusarium oxysporum f. sp. lentis (Vasd. Srin.) Gord.). The
      multilocation agronomic evaluation of both crosses showed better results for
      earliness, desirable seed yield and Fusarium wilt resistance under two agro
      ecological regions of north-western India. These better performing recombinants
      of ILL8006 * ILWL62 and ILL10829 * ILWL30 can be advanced for further genetic
      improvement and developing high yielding disease resistant cultivars of lentil.

PMID- 28751896
TI  - Proteomics Coupled with Metabolite and Cell Wall Profiling Reveal Metabolic
      Processes of a Developing Rice Stem Internode.
AB  - Internodes of grass stems function in mechanical support, transport, and, in some
      species, are a major sink organ for carbon in the form of cell wall polymers.
      This study reports cell wall composition, proteomic, and metabolite analyses of
      the rice elongating internode. Cellulose, lignin, and xylose increase as a
      percentage of cell wall material along eight segments of the second rice
      internode (internode II) at booting stage, from the younger to the older
      internode segments, indicating active cell wall synthesis. Liquid-chromatography
      tandem mass spectrometry (LC-MS/MS) of trypsin-digested proteins from this
      internode at booting reveals 2,547 proteins with at least two unique peptides in
      two biological replicates. The dataset includes many glycosyltransferases,
      acyltransferases, glycosyl hydrolases, cell wall-localized proteins, and protein
      kinases that have or may have functions in cell wall biosynthesis or remodeling.
      Phospho-enrichment of internode II peptides identified 21 unique phosphopeptides
      belonging to 20 phosphoproteins including a leucine rich repeat-III family
      receptor like kinase. GO over-representation and KEGG pathway analyses highlight
      the abundances of proteins involved in biosynthetic processes, especially the
      synthesis of secondary metabolites such as phenylpropanoids and flavonoids. LC
      MS/MS of hot methanol-extracted secondary metabolites from internode II at four
      stages (booting/elongation, early mature, mature, and post mature) indicates that
      internode secondary metabolites are distinct from those of roots and leaves, and
      differ across stem maturation. This work fills a void of in-depth proteomics and
      metabolomics data for grass stems, specifically for rice, and provides baseline
      knowledge for more detailed studies of cell wall synthesis and other biological
      processes characteristic of internode development, toward improving grass
      agronomic properties.

PMID- 28751898
TI  - Comparative Analysis of Chloroplast psbD Promoters in Terrestrial Plants.
AB  - The transcription of photosynthesis genes encoded by the plastid genome is mainly
      mediated by a prokaryotic-type RNA polymerase called plastid-encoded plastid RNA
      polymerase (PEP). Standard PEP-dependent promoters resemble bacterial sigma-70
      type promoters containing the so-called -10 and -35 elements. On the other hand,
      an unusual light- and stress-responsive promoter (psbD LRP) that is regulated by
      a 19-bp AAG-box immediately upstream of the -35 element has been mapped upstream
      of the psbD-psbC operon in some angiosperms. However, the occurrence of the AAG
      box containing psbD LRP in plant evolution remains elusive. We have mapped the
      psbD promoters in eleven embryophytes at different evolutionary stages from
      liverworts to angiosperms. The psbD promoters were mostly mapped around 500-900
      bp upstream of the psbD translational start sites, indicating that the psbD mRNAs
      have unusually long 5'-UTR extensions in common. The -10 elements of the psbD
      promoter are well-conserved in all embryophytes, but not the -35 elements. We
      found that the AAG-box sequences are highly conserved in angiosperms and
      gymnosperms except for gnetaceae plants. Furthermore, partial AAG-box-like
      sequences have been identified in the psbD promoters of some basal embryophytes
      such as moss, hornwort, and lycophyte, whereas liverwort has the standard PEP
      promoter without the AAG-box. These results suggest that the AAG-box sequences of
      the psbD LRP may have evolved from a primitive type of AAG-box of basal
      embryophytes. On the other hand, monilophytes (ferns) use another type of psbD
      promoter composed of a distinct cis-element upstream of the potential -35
      element. Furthermore, we found that psbD expression is not regulated by light in
      gymnosperms or basal angiosperms, although they have the well-conserved AAG-box
      sequences. Thus, it is unlikely that acquisition of the AAG-box containing psbD
      promoter is directly associated with light-induced transcription of the psbD-psbC
      operon. Light- and stress-induced transcription may have evolved independently
      and multiple times during terrestrial plant evolution.

PMID- 28751899
TI  - Melatonin Has the Potential to Alleviate Cinnamic Acid Stress in Cucumber
      Seedlings.
AB  - Cinnamic acid (CA), which is a well-known major autotoxin secreted by the roots
      in cucumber continuous cropping, has been proven to exhibit inhibitory regulation
      of plant morphogenesis and development. Melatonin (MT) has been recently
      demonstrated to play important roles in alleviating plant abiotic stresses. To
      investigate whether MT supplementation could improve cucumber seedling growth
      under CA stress, we treated cucumber seeds and seedlings with/without MT under CA
      or non-stress conditions, and then tested their effects on cucumber seedling
      growth, morphology, nutrient element content, and plant hormone. Overall, 10 MUM
      MT best rescued cucumber seedling growth under 0.4 mM CA stress. MT was found to
      alleviate CA-stressed seedling growth by increasing the growth rates of
      cotyledons and leaves and by stimulating lateral root growth. Additionally, MT
      increased the allocation of newly gained dry weight in roots and improved the
      tolerance of cucumber seedlings to CA stress by altering the nutrient elements
      and hormone contents of the whole plant. These results strongly suggest that the
      application of MT can effectively improve cucumber seedling tolerance to CA
      stress through the perception and integration of morphology, nutrient element
      content and plant hormone signaling crosstalk.

PMID- 28751900
TI  - Conserved Function of Fibrillin5 in the Plastoquinone-9 Biosynthetic Pathway in
      Arabidopsis and Rice.
AB  - Plastoquinone-9 (PQ-9) is essential for plant growth and development. Recently,
      we found that fibrillin5 (FBN5), a plastid lipid binding protein, is an essential
      structural component of the PQ-9 biosynthetic pathway in Arabidopsis. To
      investigate the functional conservation of FBN5 in monocots and eudicots, we
      identified OsFBN5, the Arabidopsis FBN5 (AtFBN5) ortholog in rice (Oryza sativa).
      Homozygous Osfbn5-1 and Osfbn5-2 Tos17 insertion null mutants were smaller than
      wild type (WT) plants when grown on Murashige and Skoog (MS) medium and died
      quickly when transplanted to soil in a greenhouse. They accumulated significantly
      less PQ-9 than WT plants, whereas chlorophyll and carotenoid contents were only
      mildly affected. The reduced PQ-9 content of the mutants was consistent with
      their lower maximum photosynthetic efficiency, especially under high light.
      Overexpression of OsFBN5 complemented the seedling lethal phenotype of the
      Arabidopsis fbn5-1 mutant and restored PQ-9 and PC-8 (plastochromanol-8) to
      levels comparable to those in WT Arabidopsis plants. Protein interaction
      experiments in yeast and mesophyll cells confirmed that OsFBN5 interacts with the
      rice solanesyl diphosphate synthase OsSPS2 and also with Arabidopsis AtSPS1 and
      AtSPS2. Our data thus indicate that OsFBN5 is the functional equivalent of AtFBN5
      and also suggest that the SPSs-FBN5 complex for synthesis of the solanesyl
      diphosphate tail in PQ-9 is well conserved in Arabidopsis and rice.

PMID- 28751901
TI  - Functional Characterization of TaSnRK2.8 Promoter in Response to Abiotic Stresses
      by Deletion Analysis in Transgenic Arabidopsis.
AB  - Drought, salinity, and cold are the major factors limiting wheat quality and
      productivity; it is thus highly desirable to characterize the abiotic-stress
      inducible promoters suitable for the genetic improvement of plant resistance. The
      sucrose non-fermenting 1-related protein kinase 2 (SnRK2) family genes show
      distinct regulatory properties in response to abiotic stresses. The present study
      characterized the approximately 3000-bp upstream sequence (the 313 bp upstream of
      the ATG was the transcription start site) of the Triticum aestivum TaSnRK2.8
      promoter under abscisic acid (ABA) and abiotic stresses. Four different-length 5'
      deletion fragments of TaSnRK2.8 promoter were fused with the GUS reporter gene
      and transformed into Arabidopsis. Tissue expression analysis showed that the
      TaSnRK2.8 promoter region from position -1481 to -821 contained the stalk
      specific elements, and the region from position -2631 to -1481 contained the leaf
      and root-specific elements. In the ABA-treated seedlings, the deletion analysis
      showed that the TaSnRK2.8 promoter region from position -821 to -2631 contained
      ABA response elements. The abiotic stress responses of the TaSnRK2.8 promoter
      derivatives demonstrated that they harbored abiotic-stress response elements: the
      region from position -821 to -408 harbored the osmotic-stress response elements,
      whereas the region from position -2631 to -1481 contained the positive regulatory
      motifs and the region from position -1481 to -821 contained the leaf- and stalk
      specific enhancers. Further deletion analysis of the promoter region from
      position -821 to -408 indicated that a 125-bp region from position -693 to -568
      was required to induce an osmotic-stress response. These results contribute to a
      better understanding of the molecular mechanisms of TaSnRK2.8 in response to
      abiotic stresses, and the TaSnRK2.8 promoter seems to be a candidate for
      regulating the expression of abiotic stress response genes in transgenic plants.

PMID- 28751902
TI  - Overexpression of SbSI-1, A Nuclear Protein from Salicornia brachiata Confers
      Drought and Salt Stress Tolerance and Maintains Photosynthetic Efficiency in
      Transgenic Tobacco.
AB  - A novel Salicornia brachiata Salt Inducible (SbSI-1) gene was isolated and
      overexpressed in tobacco for in planta functional validation subjected to drought
      and salt stress. SbSI-1 is a nuclear protein. The transgenic tobacco
      overexpressing SbSI-1 gene exhibited better seed germination, growth
      performances, pigment contents, cell viability, starch accumulation, and
      tolerance index under drought and salt stress. Overexpression of SbSI-1 gene
      alleviated the build-up of reactive oxygen species (ROS) and curtailed the ROS
      induced oxidative damages thus improved the physiological health of transgenic
      tobacco under stressed conditions. The higher activities of antioxidant enzymes,
      lower accumulation of ROS, higher membrane stability, relative water content, and
      polyphenol contents indicated the better survival of the transgenic tobacco than
      wild-type (WT) tobacco under stressed conditions. Transgenic tobacco had a higher
      net photosynthetic rate, PSII operating efficiency, and performance index under
      drought and salt stress. Higher accumulation of compatible solutes and K+/Na+
      ratio in transgenic tobacco than WT showed the better osmotic and redox
      homeostasis under stressed conditions. The up-regulation of genes encoding
      antioxidant enzymes (NtSOD, NtAPX, and NtCAT) and transcription factors (NtDREB2
      and NtAP2) in transgenic tobacco under stressed conditions showed the role of
      SbSI-1 in ROS alleviation and involvement of this gene in abiotic stress
      tolerance. Multivariate data analysis exhibited statistical distinction among
      growth responses, physiological health, osmotic adjustment, and photosynthetic
      responses of WT and transgenic tobacco under stressed conditions. The
      overexpression of SbSI-1 gene curtailed the ROS-induced oxidative damages and
      maintained the osmotic homeostasis under stress conditions thus improved
      physiological health and photosynthetic efficiencies of the transgenic tobacco
      overexpressing SbSI-1 gene.

PMID- 28751903
TI  - Evolution of Daily Gene Co-expression Patterns from Algae to Plants.
AB  - Daily rhythms play a key role in transcriptome regulation in plants and
      microalgae orchestrating responses that, among other processes, anticipate light
      transitions that are essential for their metabolism and development. The recent
      accumulation of genome-wide transcriptomic data generated under alternating
      light:dark periods from plants and microalgae has made possible integrative and
      comparative analysis that could contribute to shed light on the evolution of
      daily rhythms in the green lineage. In this work, RNA-seq and microarray data
      generated over 24 h periods in different light regimes from the eudicot
      Arabidopsis thaliana and the microalgae Chlamydomonas reinhardtii and
      Ostreococcus tauri have been integrated and analyzed using gene co-expression
      networks. This analysis revealed a reduction in the size of the daily rhythmic
      transcriptome from around 90% in Ostreococcus, being heavily influenced by light
      transitions, to around 40% in Arabidopsis, where a certain independence from
      light transitions can be observed. A novel Multiple Bidirectional Best Hit (MBBH)
      algorithm was applied to associate single genes with a family of potential
      orthologues from evolutionary distant species. Gene duplication, amplification
      and divergence of rhythmic expression profiles seems to have played a central
      role in the evolution of gene families in the green lineage such as Pseudo
      Response Regulators (PRRs), CONSTANS-Likes (COLs), and DNA-binding with One
      Finger (DOFs). Gene clustering and functional enrichment have been used to
      identify groups of genes with similar rhythmic gene expression patterns. The
      comparison of gene clusters between species based on potential orthologous
      relationships has unveiled a low to moderate level of conservation of daily
      rhythmic expression patterns. However, a strikingly high conservation was found
      for the gene clusters exhibiting their highest and/or lowest expression value
      during the light transitions.

PMID- 28751904
TI  - Canopy Vegetation Indices from In situ Hyperspectral Data to Assess Plant Water
      Status of Winter Wheat under Powdery Mildew Stress.
AB  - Plant disease and pests influence the physiological state and restricts the
      healthy growth of crops. Physiological measurements are considered the most
      accurate way of assessing plant health status. In this paper, we researched the
      use of an in situ hyperspectral remote sensor to detect plant water status in
      winter wheat infected with powdery mildew. Using a diseased nursery field and
      artificially inoculated open field experiments, we detected the canopy spectra of
      wheat at different developmental stages and under different degrees of disease
      severity. At the same time, destructive sampling was carried out for physical
      tests to investigate the change of physiological parameters under the condition
      of disease. Selected vegetation indices (VIs) were mostly comprised of green
      bands, and correlation coefficients between these common VIs and plant water
      content (PWC) were generally 0.784-0.902 (p < 0.001), indicating the green
      waveband may have great potential in the evaluation of water content of winter
      wheat under powdery mildew stress. The Photochemical Reflectance Index (PRI) was
      sensitive to physiological response influenced by powdery mildew, and the
      relationships of PRI with chlorophyll content, the maximum quantum efficiency of
      PSII photochemistry (Fv/Fm), and the potential activity of PSII photochemistry
      (Fv/Fo) were good with R2 = 0.639, 0.833, 0.808, respectively. Linear regressions
      showed PRI demonstrated a steady relationship with PWC across different growth
      conditions, with R2 = 0.817 and RMSE = 2.17. The acquired PRI model of wheat
      under the powdery mildew stress has a good compatibility to different
      experimental fields from booting stage to filling stage compared with the
      traditional water signal vegetation indices, WBI, FWBI1, and FWBI2. The
      verification results with independent data showed that PRI still performed better
      with R2 = 0.819 between measured and predicted, and corresponding RE = 8.26%.
      Thus, PRI is recommended as a potentially reliable indicator of PWC in winter
      wheat with powdery mildew stress. The results will help to understand the
      physical state of the plant, and provide technical support for disease control
      using remote sensing during wheat production.

PMID- 28751905
TI  - Monoterpenyl Glycosyltransferases Differentially Contribute to Production of
      Monoterpenyl Glycosides in Two Aromatic Vitis vinifera Varieties.
AB  - HIGHLIGHTS A similar trend on accumulation of glycosidically bound monoterpenes
      was observed in both varietiesTwo VvGT7 alleles mutations occurred at key sites
      in Muscat blanc a PetitVvGT14 exerted a major role in production of monoterpenyl
      glycosides in both varieties Terpenoids are the major aroma components and
      generally exist as both free and glycosidically-bound forms, of which nonvolatile
      glycosides account for a large fraction in grape berries. Our previous study has
      indicated that differential accumulation of monoterpenyl glycosides in Vitis
      vinifera "Muscat blanc a Petit" between two regions is closely correlated to
      monoterpenyl glucosyltransferase (VvGT14, XM_002285734.2) transcript abundance.
      However, it has not been determined yet whether this correlation also exists in
      other Vitis vinifera varieties. This study investigated the evolution of free and
      glycosidically bound monoterpenes in two Vitis vinifera variety "Muscat blanc a
      Petit" and "Gewurztraminer" under two vintages, and further assessed the relation
      between the accumulation of bound monoterpenes and two monoterpenyl
      glycosyltransferase transcript levels. Results showed that free monoterpenes
      exhibited three evolution patterns in both varieties during berry development of
      two vintages, whereas glycosidically bound monoterpenes showed a concentration
      elevation with berry maturation. The Cis-rose oxide and geraniol were major
      components contributing to the aroma odors of "Gewurztraminer" grapes while
      linalool was major aroma contributor to the "Muscat blanc a Petit grain" grapes.
      The accumulation of glycosidically bound monoterpenes in both varieties was
      accompanied with the high expression of VvGT7 (XM_002276510.2) and VvGT14. Only
      one allele of VvGT7 was found in the variety "Gewurztraminer" and no mutation was
      observed in its enzyme active sites. XB-VvGT7-4 and XB-VvGT7-5 were two alleles
      of VvGT7 detected in "Muscat blanc a Petit grain." The mutation on its enzyme
      active site inhibited the activity of XB-VvGT7-4, whereas VvGT7-5 exhibited an
      alteration on enzyme activity due to the insertion mutation at the position 443.
      Only one VvGT14 allele was found in both varieties, and the VvGT14 allele in both
      varieties showed the similarity on amino acid sequence. No mutation occurred in
      active sites of VvGT14 allele. These indicated that VvGT7 and VvGT14
      differentially contributed to the production of monoterpenyl glycosides in these
      Vitis Vinifera varieties.

PMID- 28751906
TI  - Observation of Extensive Chromosome Axis Remodeling during the "Diffuse-Phase" of
      Meiosis in Large Genome Cereals.
AB  - The production of balanced fertile haploid gametes requires the faithful
      separation of paired (synapsed) chromosomes toward the end of meiotic prophase I
      (desynapsis). This involves the timely dissolution of the synaptonemal complex
      during the pachytene-diplotene transition, a stage traditionally referred to as
      the "diffuse stage." In species with large genomes such as, barley (Hordeum
      vulgare L.) and wheat (Triticum aestivum L.) we know most about the early stages
      of meiotic prophase I. There, synapsis initiates at the telomeric ends of
      chromosomes and progresses toward the centromeric regions through the ordered
      assembly of the synaptonemal complex (SC). Synapsis is impacted by recombination
      (crossing over, CO) which locally modifies the extent of chromatin compaction and
      extension. CO is uneven along the chromosomes, occurring mainly toward the
      telomeric regions resulting in a highly skewed distribution of recombination
      events. However, we know very little about the process of desynapsis which occurs
      during the "diffuse stage," where the synapsed and recombined chromosomes
      faithfully desynapse and separate into daughter cells. Here, using 3D-SIM super
      resolution immuno-cytology combined with the use of antibodies directed against
      two crucial SC proteins, ASY1 and ZYP1, we followed the whole of meiosis I (i.e.,
      both synapsis and desynapsis) in both barley and wheat. We showed that synapsis
      forms a characteristic tri-partite SC structure in zygotene (more clearly seen in
      barley). Toward the end of meiosis I, as the SC starts to disassemble, we show
      that extensive chromosome axis remodeling results in the formation of
      characteristic "tinsel-like" structures in both wheat and barley. By using a
      mutant (des10) that is severely compromised in polymerization of ZYP1during
      synapsis, we show that tinsel structure formation during SC dissolution is not
      dependant on full synapsis and may relate instead to changes in expansion stress.
      Our observations highlight a potentially new role for ASYNAPSIS1 (ASY1) in
      desynapsis, in addition to chromosome synapsis and cohesion.

PMID- 28751907
TI  - Editorial: Molecular and Metabolic Mechanisms Associated with Fleshy Fruit
      Quality.

PMID- 28751908
TI  - Quantifying Gene Regulatory Relationships with Association Measures: A
      Comparative Study.
AB  - In this work, we provide a comparative study of the main available association
      measures for characterizing gene regulatory strengths. Detecting the association
      between genes (as well as RNAs, proteins, and other molecules) is very important
      to decipher their functional relationship from genomic data in bioinformatics.
      With the availability of more and more high-throughput datasets, the
      quantification of meaningful relationships by employing association measures will
      make great sense of the data. There are various quantitative measures have been
      proposed for identifying molecular associations. They are depended on different
      statistical assumptions, for different intentions, as well as with different
      computational costs in calculating the associations in thousands of genes. Here,
      we comprehensively summarize these association measures employed and developed
      for describing gene regulatory relationships. We compare these measures in their
      consistency and specificity of detecting gene regulations from both simulation
      and real gene expression profiling data. Obviously, these measures used in genes
      can be easily extended in other biological molecules or across them.

PMID- 28751909
TI  - Simultaneous Methylation-Level Assessment of Hundreds of CpG Sites by Targeted
      Bisulfite PCR Sequencing (TBPseq).
AB  - Methylated-DNA sequencing technologies are producing vast amounts of methylome
      data from cancer samples, from which cancer-associated differentially methylated
      CpG sites (cDMCs) are continuously identified and filed. The inclusion of as many
      cDMCs as possible helps improve the accuracy of cancer diagnosis and sometimes
      identify cancer subtypes. However, the lack of an established method for the
      analysis of 100s of cDMCs practically impedes their robust use in clinical
      medicine. Here, we tested the availability of targeted bisulfite-PCR-sequencing
      (TBPseq) technology for the assessment of methylation levels of a myriad of CpGs
      scattered over the genome. In randomly selected 46 cancer cell lines, multiplexed
      PCR yielded a variety of amplicons harboring 246 CpGs residing at promoters of 97
      cancer-associated genes, all of which were sequenced in the same flow cell.
      Clustering analysis of the TBPseq-assessed methylation levels of target CpGs
      showed that the lung and liver cancer cell lines correlated relatively strongly
      with each other while they weakly correlated with colon cancer cells. CpGs at the
      LIFR gene promoter, which are known to be hypermethylated in colon cancers,
      indeed were heavily methylated in the tested colon cancer cells. Moreover, the
      LIFR promoter hypermethylation was found in colon cancer cells only, but not in
      biliary tract, liver, lung, and stomach cancers cell lines. A meta-analysis with
      public cancer methylome data verified the colon cancer specificity of LIFR
      promoter methylation. These results demonstrate that our TBPseq-based methylation
      assessment could be considered an effective, accurate, and competitive method to
      simultaneously examine a large number of target cDMCs and patient samples.

PMID- 28751910
TI  - Corrigendum to "The Alliance of Mesenchymal Stem Cells, Bone, and Diabetes".
AB  - [This corrects the article DOI: 10.1155/2014/690783.].

PMID- 28751911
TI  - Corrigendum to "Male Osteoporosis in the Elderly".
AB  - [This corrects the article DOI: 10.1155/2015/907689.].

PMID- 28751912
TI  - Efficacy and Safety of Topical Corticosteroids for Management of Oral Chronic
      Graft versus Host Disease.
AB  - BACKGROUND: Oral chronic graft versus host disease (cGVHD) is a major
      complication in transplantation community, a problem that can be addressed with
      topical intervention. Topical corticosteroids are the first line of treatment
      although the choice remains challenging as none of the available treatments is
      supported by strong clinical evidence. OBJECTIVE: This systematic review aims to
      determine the clinical efficacy and safety of topical corticosteroids for the
      management of the mucosal alterations of oral cGVHD. DATA SOURCES: Electronic
      search of different databases was conducted: PubMed, Cochrane library, Grey
      literature, WHO, and clinical trials.gov for clinical trial registration as well
      as hand search in the references of relevant articles up to November 2016. DATA
      EXTRACTION: Extracted pieces of information were intervention, population, sample
      sizes, and outcomes. DATA SYNTHESIS: Six studies were included: 2 randomized
      clinical trials (RCTs), 3 cohort studies, and 1 pre-post clinical trial. RESULTS:
      There is a limited evidence concerning clinical efficacy of topical
      corticosteroids. Clobetasol, dexamethasone, and budesonide were the topical
      corticosteroid of choice. The highest level of evidence score was given to
      clobetasol followed by budesonide with a lower evidence level. CONCLUSION: All
      three topical corticosteroid preparations are effective for management of oral
      chronic GVHD with minimal easily avoided side effects.

PMID- 28751913
TI  - Cumulative Success Rate of Short and Ultrashort Implants Supporting Single Crowns
      in the Posterior Maxilla: A 3-Year Retrospective Study.
AB  - AIM: To determine cumulative success rate (CSR) of short and ultrashort implants
      in the posterior maxilla restored with single crowns. PATIENTS AND METHODS: We
      performed a retrospective study in 65 patients with 139 implants. 46 were
      ultrashort and 93 short. Implants were placed with a staged approach and restored
      with single crowns. Success rate, clinical and radiographic outcomes, and crown
      to-implant ratio (CIR) were assessed after three years. Statistical analysis was
      performed by descriptive and inferential statistics. A log-binomial regression
      model where the main outcome was implant success was achieved. Coefficients and
      95% confidence intervals were reported. Analyses were performed with Stata 13.2
      for Windows. RESULTS: 61.54% of patients were female and mean overall age was
      51.9 +/- 11.08 years old. Overall CSR was 97.1% (95% CI: 92.4-98.9): 97.9 and
      95.1% for short and ultrashort, respectively (P value: 0.33). Four implants
      failed. Covariates were not associated with CSR (P value > 0.05). Regression
      model showed coefficients correlated with implant success for ultrashort implants
      (0.87) and most of covariates but none were statistically significant (P values >
      0.05). CONCLUSIONS: Our results suggest that short and ultrashort implants may be
      successfully placed and restored with single crowns in the resorbed maxillary
      molar region.

PMID- 28751914
TI  - Geochemical Characteristics and Origins of the Crude Oil of Triassic Yanchang
      Formation in Southwestern Yishan Slope, Ordos Basin.
AB  - Biomarker compounds that derived from early living organisms play an important
      role in oil and gas geochemistry and exploration since they can record the
      diagenetic evolution of the parent materials of crude oil and reflect the organic
      geochemical characteristics of crude oil and source rocks. To offer scientific
      basis for oil exploration and exploitation for study area, gas chromatography
      mass spectrometry method is applied to study the biomarker compounds of crude oil
      in Southwestern Yishan Slope of Ordos Basin, through qualitatively and
      quantitatively analyzing separated materials. The crude oil of Yanchang Formation
      and the source rocks of Yan'an and Yanchang Formation were collected in order to
      systematically analyze the characteristics of the biomarker compounds in
      saturated hydrocarbon fractions and clarify the organic geochemical
      characteristics of crude oil. The distribution and composition of various types
      of hydrocarbon biomarker compounds in crude oil suggest that the parent materials
      of crude oil are composed of hydrobiont and terrigenous plants, and the crude oil
      is mature oil which is formed in the weak reducing fresh water environment. Oil
      source correlation results show that the crude oil of Yanchang Formation in
      Yishan Slope is sourced from the source rocks of Chang 7 subformation.

PMID- 28751915
TI  - Gene Expression and Molecular Characterization of a Xylanase from Chicken Cecum
      Metagenome.
AB  - A xylanase gene xynAMG1 with a 1,116-bp open reading frame, encoding an endo-beta
      1,4-xylanase, was cloned from a chicken cecum metagenome. The translated XynAMG1
      protein consisted of 372 amino acids including a putative signal peptide of 23
      amino acids. The calculated molecular mass of the mature XynAMG1 was 40,013 Da,
      with a theoretical pI value of 5.76. The amino acid sequence of XynAMG1 showed
      59% identity to endo-beta-1,4-xylanase from Prevotella bryantii and Prevotella
      ruminicola and 58% identity to that from Prevotella copri. XynAMG1 has two
      conserved motifs, DVVNE and TEXD, containing two active site glutamates and an
      invariant asparagine, characteristic of GH10 family xylanase. The xynAMG1 gene
      without signal peptide sequence was cloned and fused with thioredoxin protein
      (Trx.Tag) in pET-32a plasmid and overexpressed in Escherichia coli
      TunerTM(DE3)pLysS. The purified mature XynAMG1 was highly salt-tolerant and
      stable and displayed higher than 96% of its catalytic activity in the reaction
      containing 1 to 4 M NaCl. It was only slightly affected by common organic
      solvents added in aqueous solution to up to 5 M. This chicken cecum metagenome
      derived xylanase has potential applications in animal feed additives and
      industrial enzymatic processes requiring exposure to high concentrations of salt
      and organic solvents.

PMID- 28751916
TI  - Sertoli-Leydig Cell Tumor with Concurrent Rhabdomyosarcoma: Three Case Reports
      and a Review of the Literature.
AB  - Sertoli-Leydig Cell Tumors (SLCTs) make up <1% of all ovarian tumors and are
      benign or malignant, androgen-secreting tumors. Rhabdomyosarcoma (RMS) is a
      heterogeneous group of malignant tumors that resemble developing skeletal muscle.
      There have been case reports of patients with concurrent SLCT and RMS with
      limited treatment options. We aim to demonstrate treatment strategies used in our
      patients, which seemed to have prolonged survival when compared to prior case
      reports of patients not cured by surgical resection. Herein we describe 22 cases
      of SLCT with RMS elements as discussed in prior case reports and three cases from
      the authors' institution. Of the 19 cases from prior case reports, five were lost
      to follow-up and two had NED after surgical intervention. Eleven patients had
      recurrence and were deceased within one year. Of those patients not surgically
      cured, only three patients were documented as living beyond two years, all of
      whom received chemotherapy. The three patients presented from our institution had
      clinical evidence of response to chemotherapy that is traditionally used for RMS.
      In conclusion, chemotherapy with doxorubicin and ifosfamide has activity in
      patients with SLCT and RMS as does salvage chemotherapy with vincristine,
      irinotecan, and temozolomide.

PMID- 28751917
TI  - Artificial Mitochondria Transfer: Current Challenges, Advances, and Future
      Applications.
AB  - The objective of this review is to outline existing artificial mitochondria
      transfer techniques and to describe the future steps necessary to develop new
      therapeutic applications in medicine. Inspired by the symbiotic origin of
      mitochondria and by the cell's capacity to transfer these organelles to damaged
      neighbors, many researchers have developed procedures to artificially transfer
      mitochondria from one cell to another. The techniques currently in use today
      range from simple coincubations of isolated mitochondria and recipient cells to
      the use of physical approaches to induce integration. These methods mimic natural
      mitochondria transfer. In order to use mitochondrial transfer in medicine, we
      must answer key questions about how to replicate aspects of natural transport
      processes to improve current artificial transfer methods. Another priority is to
      determine the optimum quantity and cell/tissue source of the mitochondria in
      order to induce cell reprogramming or tissue repair, in both in vitro and in vivo
      applications. Additionally, it is important that the field explores how
      artificial mitochondria transfer techniques can be used to treat different
      diseases and how to navigate the ethical issues in such procedures. Without a
      doubt, mitochondria are more than mere cell power plants, as we continue to
      discover their potential to be used in medicine.

PMID- 28751918
TI  - Cellular Responses in Human Dental Pulp Stem Cells Treated with Three Endodontic
      Materials.
AB  - Human dental pulp stem cells (HDPSCs) are of special relevance in future
      regenerative dental therapies. Characterizing cytotoxicity and genotoxicity
      produced by endodontic materials is required to evaluate the potential for
      regeneration of injured tissues in future strategies combining regenerative and
      root canal therapies. This study explores the cytotoxicity and genotoxicity
      mediated by oxidative stress of three endodontic materials that are widely used
      on HDPSCs: a mineral trioxide aggregate (MTA-Angelus white), an epoxy resin
      sealant (AH-Plus cement), and an MTA-based cement sealer (MTA-Fillapex). Cell
      viability and cell death rate were assessed by flow cytometry. Oxidative stress
      was measured by OxyBlot. Levels of antioxidant enzymes were evaluated by Western
      blot. Genotoxicity was studied by quantifying the expression levels of DNA damage
      sensors such as ATM and RAD53 genes and DNA damage repair sensors such as RAD51
      and PARP-1. Results indicate that AH-Plus increased apoptosis, oxidative stress,
      and genotoxicity markers in HDPSCs. MTA-Fillapex was the most cytotoxic oxidative
      stress inductor and genotoxic material for HDPSCs at longer times in preincubated
      cell culture medium, and MTA-Angelus was less cytotoxic and genotoxic than AH
      Plus and MTA-Fillapex at all times assayed.

PMID- 28751919
TI  - Intra-Articular Injection of Human Synovial Membrane-Derived Mesenchymal Stem
      Cells in Murine Collagen-Induced Arthritis: Assessment of Immunomodulatory
      Capacity In Vivo.
AB  - The aim of this study was to evaluate the efficacy of human synovial membrane
      derived MSCs (SM-MSCs) in murine collagen-induced arthritis (CIA). Male mice (age
      7-9 weeks) were injected intra-articularly with SM-MSCs obtained from patients
      with osteoarthritis, on days 28, 32, and 38 after bovine type II collagen
      immunization. The efficacy of SM-MSCs in CIA was evaluated clinically and
      histologically. Cytokine profile analyses were performed by real-time polymerase
      chain reaction and multiplex analyses. Splenic helper T (Th) cell and regulatory
      B cell subsets were analyzed by flow cytometry. Intra-articular SM-MSC injection
      ameliorated the clinical and histological severity of arthritis. Decrease in
      tumor necrosis factor-alpha, interferon-gamma, and interleukin- (IL-) 17A and
      increase in IL-10 production were observed after SM-MSC treatment. Flow cytometry
      showed that Th1 and Th17 cells decreased, whereas Th2, regulatory T (Treg), and
      PD-1+CXCR5+FoxP3+ follicular Treg cells increased in the spleens of SM-MSC
      treated mice. Regulatory B cell analysis showed that CD21hiCD23hi transitional 2
      cells, CD23lowCD21hi marginal zone cells, and CD19+CD5+CD1d+IL-10+ regulatory B
      cells increased following SM-MSC treatment. Our results demonstrated that SM-MSCs
      injected in inflamed joints in CIA had a therapeutic effect and could prevent
      arthritis development and suppress immune responses via immunoregulatory cell
      expansion.

PMID- 28751920
TI  - Common Clinical Characteristics and Rare Medical Problems of Fragile X Syndrome
      in Thai Patients and Review of the Literature.
AB  - Background. Clinical characteristics of fragile X syndrome (FXS) have been well
      documented in Caucasians, whereas in Asians they have rarely been described.
      Those that have been conducted used small cohorts that utilized DNA for diagnosis
      and larger cohorts that utilized cytogenetics for diagnosis. This study is to
      describe clinical characteristics of FXS in a large cohort of Thai patients
      diagnosed by standard molecular methods. Methods. Seventy-seven index cases and
      46 affected relatives diagnosed with FXS were recruited into the study. To
      determine frequencies of common characteristics of FXS in prepubertal boys, we
      reviewed 56 unrelated cases aged between 18 and 146 months. To list rare medical
      problems, we reviewed 75 cases aged between 8 months to 71 years old, including
      53 index cases and 22 affected relatives. In addition, we selected 16 clinical
      studies from various ethnicities for comparison with our findings. Results. In
      prepubertal boys with FXS, attention deficit and/or hyperactivity, prominent
      ears, macroorchidism, and elongated face were observed in 96%, 80%, 53%, and 48%
      of patients, respectively, whereas recognizable X-linked inheritance presented in
      11% of patients. IQ scores ranged between 30 and 64 (mean +/- SD = 43 +/- 9, n =
      25). We observed clinical findings that rarely or have never been reported, for
      example, medulloblastoma and tetralogy of Fallot. Conclusion. Attention deficit
      and/or hyperactivity and prominent ear are the most common behavioral and
      physical features in prepubertal boys with FXS, respectively. There are
      differences in frequencies of clinical characteristics observed between
      ethnicities; however, it is difficult to draw a solid conclusion due to different
      recruitment criteria and sample sizes within each study.

PMID- 28751921
TI  - Evaluation of Anti-Inflammatory Activities of Qingre-Qushi Recipe (QRQS) against
      Atopic Dermatitis: Potential Mechanism of Inhibition of IL-33/ST2 Signal
      Transduction.
AB  - To evaluate the anti-inflammatory activities of QRQS against AD and the
      inhibitory molecular mechanisms of IL-33/ST2 signal transduction, BALB/c mice
      were divided into six groups (normal control, OVA control, low-dose of QRQS,
      middle-dose of QRQS, high-dose of QRQS, and cetirizine) and epicutaneously
      exposed to ovalbumin or PBS for 3 weeks and treated with QRQS for 2 weeks. Skin
      biopsies and blood samples were obtained for histological study, antibody
      analysis, and RNA isolation. HaCaT cells, stimulated by TNF-alpha and IFN-gamma,
      were treated with QRQS to evaluate mRNA and protein expression by RT-PCR and
      ELISA. QRQS decreased both epidermal and dermal thickness, alleviated dermatitis,
      and reduced IL-33 and ST2 positive cell numbers. The concentration of specific
      IgE, IgG, IgG1, and IgG2a antibodies in serum and the expression of IL-33, ST2,
      IL-1RAcP, IL-4, and IL-13 mRNA in the skin were suppressed. No significant
      difference exists in TNF-alpha or IFN-gamma. QRQS decreased IL-33 mRNA and
      protein secretion in HaCaT cells exposed to TNF-alpha and IFN-gamma in a time-
      and concentration-dependent manner. QRQS regulates related molecule expression of
      ovalbumin-induced dermatitis involved in the IL-33/ST2 signaling axis in the
      treatment of acute AD.

PMID- 28751922
TI  - Clinical Effect of Electroacupuncture on Lung Injury Patients Caused by Severe
      Acute Pancreatitis.
AB  - This study aimed to investigate the effects of electroacupuncture at the Lieque,
      Chize, and Zusanli points in patients with lung injury caused by severe acute
      pancreatitis. Patients with acute respiratory distress syndrome (ARDS) induced by
      severe acute pancreatitis (SAP) were randomly divided into three groups based on
      the treatment: conventional therapy alone (group A), electroacupuncture of
      nonacupoints with conventional therapy (group B), and electroacupuncture at the
      Lieque (LU7), Chize (LU5), and Zusanli (ST36) points (group C) once a day for 5
      days. Arterial blood samples were obtained for blood gas analysis before
      electroacupuncture (T1) and 3 (T2) and 5 (T3) days after electroacupuncture. The
      oxygenation index was significantly higher in all groups at T2 and T3 than that
      at T1, while the APACHE-II scores were decreased significantly. The expression of
      TNF-alpha was significantly decreased and the IL-10 was significantly increased
      in all groups at T3. The oxygenation index at T2 and T3 was significantly higher
      in group C than that in group B. Electroacupuncture at Lieque, Chize, and Zusanli
      can lessen the lung injury induced by SAP, and the mechanism may be related to
      the decreased TNF-alpha and increased IL-10 value. Clinical Registration Number
      is ChiCTR-ICR-15006850.

PMID- 28751924
TI  - Corrigendum to "A Clinical Decision Support System for the Diagnosis, Fracture
      Risks and Treatment of Osteoporosis".
AB  - [This corrects the article DOI: 10.1155/2015/189769.].

PMID- 28751923
TI  - Role of BDNF/TrkB pathway in the visual system: Therapeutic implications for
      glaucoma.
AB  - INTRODUCTION: Neuroprotective therapeutics are needed to treat glaucoma, an optic
      neuropathy that results in death of retinal ganglion cells (RGCs). AREAS COVERED:
      The BDNF/TrkB pathway is important for RGC survival. Temporal and spatial
      alterations in the BDNF/TrkB pathway occur in development and in response to
      acute optic nerve injury and to glaucoma. In animal models, BDNF supplementation
      is successful at slowing RGC death after acute optic nerve injury and in
      glaucoma, however, the BDNF/TrkB signaling is not the only pathway supporting
      long term RGC survival. EXPERT COMMENTARY: Much remains to be discovered about
      the interaction between retrograde, anterograde, and retinal BDNF/TrkB signaling
      pathways in both neurons and glia. An ideal therapeutic agent for glaucoma likely
      has several modes of action that target multiple mechanisms of neurodegeneration
      including the BDNF/TrkB pathway.

PMID- 28751925
TI  - Effects of dialectical behavior therapy skills training on outcomes for mental
      health staff in a child and adolescent residential setting.
AB  - Training in Dialectical Behavior Therapy (DBT) skills coaching is desirable for
      staff in psychiatric settings, due to the efficacy of DBT in treating difficult
      patient populations. In such settings, training resources are typically limited,
      and staff turnover is high, necessitating brief training. This study evaluated
      the effects of a brief training in DBT skills coaching for nursing staff working
      in a child and adolescent psychiatric residential program. Nursing staff (n = 22)
      completed assessments of DBT skill knowledge, burnout, and stigma towards
      patients with borderline personality disorder (BPD) before and after a six-week
      DBT skills coaching training. Repeated measure ANOVAs were conducted to examine
      changes on all measures from pre- to post- treatment and hierarchical linear
      regressions to examine relationships between pre- training DBT knowledge,
      burnout, and BPD stigma and these same measures post-training. The brief DBT
      skill coaching training significantly increased DBT knowledge (p = .007) and
      decreased staff personal (p = .02) and work (p = .03) burnout and stigma towards
      BPD patients (p = .02). Burnout indices and BPD stigma were highly correlated at
      both time points (p < .001); however, while pre-training BPD stigma significantly
      predicted post-training client burnout (p = .04), pre-training burnout did not
      predict post-training BPD stigma. These findings suggest that brief training of
      psychiatric nursing staff in DBT skills and coaching techniques can result in
      significant benefits, including reduced staff burnout and stigma toward patients
      with BPD-related problems, and that reducing BPD stigma may particularly promote
      lower burnout.

PMID- 28751926
TI  - Origin of the Strong Interaction between Polar Molecules and Copper(II) Paddle
      Wheels in Metal Organic Frameworks.
AB  - The copper paddle-wheel is the building unit of many metal organic frameworks.
      Because of the ability of the copper cations to attract polar molecules, copper
      paddle-wheels are promising for carbon dioxide adsorption and separation. They
      have therefore been studied extensively, both experimentally and computationally.
      In this work we investigate the copper-CO2 interaction in HKUST-1 and in two
      different cluster models of HKUST-1: monocopper Cu(formate)2 and dicopper
      Cu2(formate)4. We show that density functional theory methods severely
      underestimate the interaction energy between copper paddle-wheels and CO2, even
      including corrections for the dispersion forces. In contrast, a multireference
      wave function followed by perturbation theory to second order using the CASPT2
      method correctly describes this interaction. The restricted open-shell Moller
      Plesset 2 method (ROS-MP2, equivalent to (2,2) CASPT2) was also found to be
      adequate in describing the system and used to develop a novel force field. Our
      parametrization is able to predict the experimental CO2 adsorption isotherms in
      HKUST-1, and it is shown to be transferable to other copper paddle-wheel systems.

PMID- 28751927
TI  - An NMR Crystallographic Investigation of the Relationships between the Crystal
      Structure and 29Si Isotropic Chemical Shift in Silica Zeolites.
AB  - NMR crystallography has recently been applied to great effect for silica
      zeolites. Here we investigate whether it is possible to extend the structural
      information available from routine NMR spectra via a simple structure-spectrum
      relationship. Unlike previous empirically derived relationships that have
      compared experimental crystal structures for (often disordered) silicates with
      experimental NMR spectra, where the structure may not be an accurate
      representation of the material studied experimentally, we use NMR parameters
      calculated by density functional theory (DFT) for both model Si(OSi(OH)3)4
      clusters and also extended zeolitic SiO2 frameworks, for which the input
      structure corresponding to the NMR parameters is known exactly. We arrive at a
      structure-spectrum relationship dependent on the mean Si-O bond length, mean Si-O
      Si bond angle, and the standard deviations of both parameters, which can predict
      to within 1.3 ppm the 29Si isotropic magnetic shielding that should be obtained
      from a DFT calculation. While this semiempirical relationship will never
      supersede DFT where this is possible, it does open up the possibility of a rapid
      estimation of the outcome of a DFT calculation where the actual calculation would
      be prohibitively costly or otherwise challenging. We also investigate the
      structural optimization of SiO2 zeolites using DFT, demonstrating that the mean
      Si-O bond lengths all tend to 1.62 A and the distortion index tends to <2.0
      degrees , suggesting that these metrics may be suitable for rapid validation of
      whether a given crystal structure represents a realistic local geometry around
      Si, or merely a bulk average with contributions from several different local
      geometries.

PMID- 28751928
TI  - A Decrease of Brain MicroRNA-122 Level Is an Early Marker of Cerebrovascular
      Disease in the Stroke-Prone Spontaneously Hypertensive Rat.
AB  - Based on preliminary evidence that highlights microRNA-122 as a contributing
      factor to stroke pathogenesis, we aimed at assessing its expression level, along
      with the presence of early signs of cerebrovascular disease, in the brain of
      stroke-prone spontaneously hypertensive rat (SHRSP), a suitable model of human
      disease that accelerates stroke occurrence under a high sodium/low potassium
      (Japanese-style) diet (JD). After one month of JD, before stroke occurrence,
      brain microRNA-122 level was significantly decreased in SHRSP as compared to the
      stroke-resistant SHR (SHRSR). At this time, levels of markers of oxidative stress
      and inflammation, as well as of endothelial integrity and function, apoptosis and
      necrosis were differently modulated in the brains of JD-fed SHRSP as compared to
      SHRSR, pointing to a significant activation of all deleterious mechanisms
      underlying subsequent stroke development in SHRSP. We also showed that miR-122
      improved survival of rat endothelial cerebral cells upon stress stimuli (excess
      NaCl, hydrogen peroxide). Our data suggest that a decrease of brain microRNA-122
      level is deleterious and can be considered as an early marker of stroke in the
      SHRSP. Understanding the mechanisms by which microRNA-122 protects vascular cells
      from stress stimuli may provide a useful approach to improve preventive and
      treatment strategies against stroke.

PMID- 28751929
TI  - The Preconditioning of Berberine Suppresses Hydrogen Peroxide-Induced Premature
      Senescence via Regulation of Sirtuin 1.
AB  - With a long history of application in Chinese traditional medicine, berberine
      (BBR) was reported to exhibit healthspan-extending properties in some age-related
      diseases, such as type 2 diabetes and atherosclerosis. However, the antiaging
      mechanism of BBR is not completely clear. By means of hydrogen peroxide- (H2O2-)
      induced premature cellular senescence model, we found that a low-concentration
      preconditioning of BBR could resist premature senescence in human diploid
      fibroblasts (HDFs) measured by senescence-associated beta-galactosidase (SA-beta
      gal), accompanied by a decrease in loss of mitochondrial membrane potential and
      production of intracellular reactive oxygen species (ROS). Moreover, the low
      concentration preconditioning of BBR could make cells less susceptible to
      subsequent H2O2-induced cell cycle arrest and growth inhibition. Experimental
      results further showed that the low concentration of BBR could induce a slight
      increase of ROS and upregulate the expression level of sirtuin 1 (SIRT1), an
      important longevity regulator. H2O2-induced activation of checkpoint kinase 2
      (Chk2) was significantly attenuated after the preconditioning of BBR. The present
      findings implied that the low-concentration preconditioning of BBR could have a
      mitohormetic effect against cellular senescence triggered by oxidative stress in
      some age-related diseases through the regulation of SIRT1.

PMID- 28751930
TI  - The Correlation between Chemical Structures and Antioxidant, Prooxidant, and
      Antitrypanosomatid Properties of Flavonoids.
AB  - Flavonoids have demonstrated in vivo and in vitro leishmanicidal, trypanocidal,
      antioxidant, and prooxidant properties. The chemotherapy of trypanosomiasis and
      leishmaniasis lacks efficacy, presents high toxicity, and is related to the
      development of drug resistance. Thus, a series of 40 flavonoids were investigated
      with the purpose of correlating these properties via structure and activity
      analyses based on integrated networks and QSAR models. The classical groups for
      the antioxidant activity of flavonoids were combined in order to explain the
      influence of antioxidant and prooxidant activities on the antiparasitic
      properties. These analyses become useful for the development of efficient
      treatments for leishmaniasis and trypanosomiasis. Finally, the dual activity of
      flavonoids presenting both anti- and prooxidant activities revealed that the
      existence of a balance between these two features could be important to the
      development of adequate therapeutic strategies.

PMID- 28751931
TI  - A Review of the Molecular Mechanisms Underlying the Development and Progression
      of Cardiac Remodeling.
AB  - Pathological molecular mechanisms involved in myocardial remodeling contribute to
      alter the existing structure of the heart, leading to cardiac dysfunction. Among
      the complex signaling network that characterizes myocardial remodeling, the
      distinct processes are myocyte loss, cardiac hypertrophy, alteration of
      extracellular matrix homeostasis, fibrosis, defective autophagy, metabolic
      abnormalities, and mitochondrial dysfunction. Several pathophysiological stimuli,
      such as pressure and volume overload, trigger the remodeling cascade, a process
      that initially confers protection to the heart as a compensatory mechanism. Yet
      chronic inflammation after myocardial infarction also leads to cardiac remodeling
      that, when prolonged, leads to heart failure progression. Here, we review the
      molecular pathways involved in cardiac remodeling, with particular emphasis on
      those associated with myocardial infarction. A better understanding of cell
      signaling involved in cardiac remodeling may support the development of new
      therapeutic strategies towards the treatment of heart failure and reduction of
      cardiac complications. We will also discuss data derived from gene therapy
      approaches for modulating key mediators of cardiac remodeling.

PMID- 28751932
TI  - Does Regular Exercise Counter T Cell Immunosenescence Reducing the Risk of
      Developing Cancer and Promoting Successful Treatment of Malignancies?
AB  - Moderate intensity aerobic exercise training or regular physical activity is
      beneficial for immune function. For example, some evidence shows that individuals
      with an active lifestyle exhibit stronger immune responses to vaccination
      compared to those who are inactive. Encouragingly, poor vaccine responses, which
      are characteristic of an ageing immune system, can be improved by single or
      repeated bouts of exercise. In addition, exercise-induced lymphocytosis, and the
      subsequent lymphocytopenia, is thought to facilitate immune surveillance, whereby
      lymphocytes search tissues for antigens derived from viruses, bacteria, or
      malignant transformation. Aerobic exercise training is anti-inflammatory and is
      linked to lower morbidity and mortality from diseases with infectious,
      immunological, and inflammatory aetiologies, including cancer. These observations
      have led to the view that aerobic exercise training might counter the age
      associated decline in immune function, referred to as immunosenescence. This
      article summarises the aspects of immune function that are sensitive to exercise
      induced change, highlighting the observations which have stimulated the idea that
      aerobic exercise training could prevent, limit, or delay immunosenescence,
      perhaps even restoring aged immune profiles. These potential exercise-induced
      anti-immunosenescence effects might contribute to the mechanisms by which active
      lifestyles reduce the risk of developing cancer and perhaps benefit patients
      undergoing cancer therapy.

PMID- 28751933
TI  - The Central Role of Biometals Maintains Oxidative Balance in the Context of
      Metabolic and Neurodegenerative Disorders.
AB  - Traditionally, oxidative stress as a biological aspect is defined as an imbalance
      between the free radical generation and antioxidant capacity of living systems.
      The intracellular imbalance of ions, disturbance in membrane dynamics, hypoxic
      conditions, and dysregulation of gene expression are all molecular pathogenic
      mechanisms closely associated with oxidative stress and underpin systemic changes
      in the body. These also include aspects such as chronic immune system activation,
      the impairment of cellular structure renewal, and alterations in the character of
      the endocrine secretion of diverse tissues. All of these mentioned features are
      crucial for the correct function of the various tissue types in the body. In the
      present review, we summarize current knowledge about the common roots of
      metabolic and neurodegenerative disorders induced by oxidative stress. We discuss
      these common roots with regard to the way that (1) the respective metal ions are
      involved in the maintenance of oxidative balance and (2) the metabolic and
      signaling disturbances of the most important biometals, such as Mg2+, Zn2+, Se2+,
      Fe2+, or Cu2+, can be considered as the central connection point between the
      pathogenesis of both types of disorders and oxidative stress.

PMID- 28751934
TI  - Activation of p47phox as a Mechanism of Bupivacaine-Induced Burst Production of
      Reactive Oxygen Species and Neural Toxicity.
AB  - Bupivacaine has been shown to induce neurotoxicity through inducing excessive
      reactive oxygen species (ROS), but the underlying mechanism remains unclear. NOX2
      is one of the most important sources of ROS in the nervous system, and its
      activation requires the membrane translocation of subunit p47phox. However, the
      role of p47phox in bupivacaine-induced neurotoxicity has not been explored. In
      our in vitro study, cultured human SH-SY5Y neuroblastoma cells were treated with
      1.5 mM bupivacaine to induce neurotoxicity. Membrane translocation of p47phox was
      assessed by measuring the cytosol/membrane ratio of p47phox. The effects of the
      NOX inhibitor VAS2870 and p47phox-siRNA on bupivacaine-induced neurotoxicity were
      investigated. Furthermore, the effect of VAS2870 on bupivacaine-induced
      neurotoxicity was assessed in vivo in rats. All these changes were reversed by
      pretreatment with VAS2870 or transfection with p47phox-siRNA in SH-SY5Y cells.
      Similarly, pretreatment with VAS2870 attenuated bupivacaine-induced neuronal
      toxicity in rats. It is concluded that enhancing p47phox membrane translocation
      is a major mechanism whereby bupivacaine induced neurotoxicity and that
      pretreatment with VAS2870 or local p47phox gene knockdown attenuated bupivacaine
      induced neuronal cell injury.

PMID- 28751935
TI  - Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of
      Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and
      Chromatin Binding.
AB  - Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage
      response bypass and tumorigenesis in our model of hydrogen peroxide-associated
      ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related
      dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative
      stress. In the UC model, we have observed features of oncogenic transformation:
      increased proliferation, undetected DNA damage, and apoptosis resistance. Here,
      we show that Chk1 was downregulated but activated in the acute and quiescent
      chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by
      suppressing JNK activation following oxidative stress, promoting cell cycle
      progression despite DNA damage. Simultaneously, activated Chk1 was bound to
      chromatin. This triggered histone acetylation and the binding of histone
      acetyltransferases and transcription factors to chromatin. Thus, chromatin
      immobilized activated Chk1 executed a dual function by suppressing DNA damage
      response and simultaneously inducing chromatin modulation. This caused undetected
      DNA damage and increased cellular proliferation through failure to transmit the
      appropriate DNA damage signal. Findings in vitro were corroborated by chromatin
      accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in
      vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel
      therapeutic strategy to prevent UC-related tumor progression.

PMID- 28751936
TI  - Maresin 1 Ameliorates Lung Ischemia/Reperfusion Injury by Suppressing Oxidative
      Stress via Activation of the Nrf-2-Mediated HO-1 Signaling Pathway.
AB  - Lung ischemia/reperfusion (I/R) injury occurs in various clinical conditions and
      heavily damaged lung function. Oxidative stress reaction and antioxidant enzymes
      play a pivotal role in the etiopathogenesis of lung I/R injury. In the current
      study, we investigated the impact of Maresin 1 on lung I/R injury and explored
      the possible mechanism involved in this process. MaR 1 ameliorated I/R-induced
      lung injury score, wet/dry weight ratio, myeloperoxidase, tumor necrosis factor,
      bronchoalveolar lavage fluid (BALF) leukocyte count, BALF neutrophil ratio, and
      pulmonary permeability index levels in lung tissue. MaR 1 significantly reduced
      ROS, methane dicarboxylic aldehyde, and 15-F2t-isoprostane generation and
      restored antioxidative enzyme (superoxide dismutase, glutathione peroxidase, and
      catalase) activities. Administration of MaR 1 improved the expression of nuclear
      Nrf-2 and cytosolic HO-1 in I/R-treated lung tissue. Furthermore, we also found
      that the protective effects of MaR 1 on lung tissue injury and oxidative stress
      were reversed by HO-1 activity inhibitor, Znpp-IX. Nrf-2 transcription factor
      inhibitor, brusatol, significantly decreased MaR 1-induced nuclear Nrf-2 and
      cytosolic HO-1 expression. In conclusion, these results indicate that MaR 1
      protects against lung I/R injury through suppressing oxidative stress. The
      mechanism is partially explained by activation of the Nrf-2-mediated HO-1
      signaling pathway.

PMID- 28751937
TI  - Myricitrin Modulates NADPH Oxidase-Dependent ROS Production to Inhibit Endotoxin
      Mediated Inflammation by Blocking the JAK/STAT1 and NOX2/p47phox Pathways.
AB  - Myricitrin, a naturally occurring polyphenol hydroxy flavonoid, has been reported
      to possess anti-inflammatory properties. However, the precise molecular mechanism
      of myricitrin's effects on LPS-induced inflammation is unclear. In the present
      study, myricitrin significantly alleviated acute lung injury in mice. Myricitrin
      also markedly suppressed the production of NO, TNF-alpha, IL-6, and MCP-1 in
      RAW264.7 macrophage cells. The inhibition of NO was concomitant with a decrease
      in the protein and mRNA levels of iNOS. The phosphorylation of JAKs and STAT-1
      was abrogated by myricitrin. Furthermore, myricitrin inhibited the nuclear
      transfer and DNA binding activity of STAT1. The JAK-specific inhibitor
      ruxolitinib simulated the anti-inflammatory effect of myricitrin. However,
      myricitrin had no impact on the MAPK signalling pathway. Myricitrin attenuated
      the generation of intracellular ROS by inhibiting the assembly of components of
      the gp91phox and p47phox. Suppression of ROS generation using NAC or apocynin or
      by silencing gp91phox and p47phox all demonstrated that decreasing the level of
      ROS inhibited the LPS-induced inflammatory response. Collectively, these results
      confirmed that myricitrin exhibited anti-inflammatory activity by blocking the
      activation of JAKs and the downstream transcription factor STAT1, which may
      result from the downregulation of NOX2-dependent ROS production mediated by
      myricitrin.

PMID- 28751938
TI  - LED Lights With Hidden Intensity-Modulated Blue Channels Aiming for Enhanced
      Subconscious Visual Responses.
AB  - A new form of light-emitting diode (LED) light suitable for general illumination
      is proposed to enhance subconscious, nonimage-forming visual responses, which are
      essential to our well-being. Pulsing light has been shown to reduce photoreceptor
      adaptation and elicit stronger subconscious visual responses at an indoor
      illumination level. Using the silent substitution technique, a melanopsin
      selective flicker can be added into white light. A linear optimization algorithm
      was developed to suppress any perceivable fluctuation of light intensity and
      colors of illuminated objects. Two examples of lights are given to illustrate the
      potential applications of the proposed multi-LED light for general illumination
      and therapeutic purposes.

PMID- 28751939
TI  - A Comparative Assessment of Postoperative Analgesic Efficacy of Lornoxicam versus
      Tramadol after Open Reduction and Internal Fixation of Mandibular Fractures.
AB  - Pain after any surgical procedure is inevitable but can be controlled by
      administration of analgesics in most cases. Postoperative pain after surgical
      treatment of mandibular fractures can be treated by nonsteroidal anti
      inflammatory drugs (NSAIDs) and opioid analgesics. The purpose of this study is
      to critically compare the postoperative analgesic efficacy of small doses of
      intravenous TRAMADOL (opioid analgesic) versus LORNOXICAM (NSAID) in patients
      with mandibular trauma undergoing open reduction and internal fixation (ORIF) and
      to assess the presence of any adverse effects due to NSAID or opioid use. Forty
      adult ASA grade I-II patients with mandibular trauma, scheduled for ORIF under
      general anesthesia in the Department of Oral and Maxillofacial Surgery, College
      of Dental Sciences, Davangere, were selected for the study. The patients were
      randomly assigned into a tramadol group (Group T) and a lornoxicam group (Group
      L) and were administered intravenous tramadol 50 mg and intravenous lornoxicam 8
      mg, respectively, at specific postoperative intervals. Pain intensity was
      quantitatively assessed at the 2nd, 4th, 6th, 12th, and 24th postoperative hours
      using a visual analog scale of 10 cm. Adverse effects of the analgesics were also
      recorded and compared. Both the drugs resulted in a significant decrease in pain
      intensity from 2nd to 24th postoperative hours, but better pain control was
      observed in Group L at 24th postoperative hour. Only two patients experienced
      nausea and vomiting in Group T and one patient experienced gastric acidity in
      Group L. The comparative results clearly demonstrate that pain control by
      intravenous lornoxicam is significantly better than by intravenous tramadol at
      24th postoperative hour after ORIF of mandibular trauma. Side effects produced by
      both the drugs were minor and had no apparent effect on the study results.

PMID- 28751941
TI  - Did King Philip II of Ancient Macedonia Suffer a Zygomatico-Orbital Fracture? A
      Maxillofacial Surgeon's Approach.
AB  - Philip II, father of Alexander the Great, succeeded his brother, Perdiccas III,
      to the throne of Macedonia in 360 BC. He has been described by historians as a
      generous king and military genius who managed to achieve his ambitious plans by
      expanding the Macedonian city-state over the whole Greek territory and the
      greater part of the Balkan Peninsula. The aim of our study was to present the
      evidence with regard to the facial injury of King Philip II of Macedonia and
      discuss the treatment of the wound by his famous physician, Critobulos. We
      reviewed the literature for historical, archaeological, and paleopathological
      evidence of King Philip's facial injury. We include a modern reconstruction of
      Philip's face based on the evidence of his injury by a team of anatomists and
      archaeologists from the Universities of Bristol and Manchester. In the light of
      the archaeological findings by Professor Andronikos and the paleopathological
      evidence by Musgrave, it can be claimed with confidence that King Philip II
      suffered a significant injury of his zygomaticomaxillary complex and supraorbital
      rim caused by an arrow as can be confirmed in many historical sources. To the
      best of our knowledge, this is the first attempt to present the trauma of King
      Philip II from a maxillofacial surgeon's point of view.

PMID- 28751940
TI  - Nasal Valve Reconstruction Using a Titanium Implant: An Outcomes Study.
AB  - Septoplasty alone is not always sufficient to correct nasal obstruction. Various
      techniques have been employed to repair nasal valve collapse and improve airflow.
      This article aimed to evaluate outcomes and quality of life following nasal valve
      reconstruction using a titanium implant in patients with nasal valve collapse.
      This is a single-center retrospective study that consisted of a telephone
      questionnaire of 37 quality-of-life measures and questions related to the
      surgical procedure and recovery process to evaluate postsurgical outcomes.
      Fifteen patients completed the survey. There was a significant improvement in
      nasal blockage/obstruction, breathing through the nose, sleeping, breathing
      through nose during exercise, the need to blow nose, sneezing, facial
      pain/pressure, fatigue, productivity, and restlessness/irritability after
      surgery. Overall, 100% of patients were satisfied with the results and would
      recommend this procedure. The most common postoperative complaints were pain
      (33%) and difficulty breathing (33%). Patients noticed no increase (20%) or a
      slight increase (73%) in the size of their nose. Sixty percent of patients cannot
      see the implant and 13% report the implant is barely noticeable. Nasal valve
      repair with a titanium implant was successful at improving symptoms of nasal
      obstruction and other quality-of-life issues. Satisfaction was high among all
      patients. The implants are palpable, thought to be visible by some patients, yet
      accepted by the majority of patients. This approach may be especially important
      in patients with prior nasal surgery but continue to experience refractory
      symptoms.

PMID- 28751942
TI  - Treatment of Mandibular Angle Fractures with Single Three-Dimensional Locking
      Miniplates without Maxillomandibular Fixation: How Much Fixation Is Required?
AB  - The aim of this simple nonrandomized and observational study was to evaluate the
      efficacy of single three-dimensional (3D) plate for the treatment of mandibular
      angle fractures without maxillomandibular fixation. A total of 30 patients with
      noncomminuted fractures of mandibular angle requiring open reduction and internal
      fixation were included in the study. All the patients were treated by open
      reduction and internal fixation using single 3D titanium locking miniplate placed
      with the help of transbuccal trocar or Synthes 90-degree hand piece and screw
      driver. 3D locking titanium miniplates used in our study was four-holed, box
      shaped plate, and screws with 2 mm diameter and 8 mm length. The following
      clinical parameters were assessed for each patient at each follow-up visit: pain
      (visual analog scale: 0-5), swelling (visual analog scale: 0-5), mouth opening,
      infection, paresthesia, hardware failure (plate fracture), occlusal
      discrepancies, and mobility between fracture fragments. A significant decrease in
      pain level was seen during the follow-up visits. No statistically significant
      changes were seen in swelling, but mouth opening increased in the subsequent
      visits. Also better results were seen in terms of fracture stability and
      occlusion in the postoperative period. Two cases of infection and two cases of
      hardware failure were noted in sixth postoperative week. 3D plating system is an
      easy to use alternative to conventional miniplates to treat mandibular angle
      fractures that uses lesser foreign material, thus reducing the operative time and
      overall cost of the treatment. Better fracture stability and occlusion was also
      achieved using the 3D plating system.

PMID- 28751943
TI  - Helmet Wear and Craniofacial Trauma Burden: A Plea for Regulations Mandating
      Protective Helmet Wear.
AB  - Helmet wear offers protection in various ways against craniomaxillofacial and
      brain trauma. The specific pattern and overall burden of craniofacial trauma
      among helmeted and unhelmeted patients has not been well defined. This is a
      retrospective review of trauma patients involved in documented helmet-associated
      injuries that presented to the Mayo Clinic Emergency Department in Rochester,
      Minnesota, and completed initial trauma evaluation between 1999 and 2015. A total
      of 417 patients (50% unhelmeted, 82% male) were identified. The median age at
      injury was 22.9 years (interquartile range [IQR]: 15.2-44.2]) and median follow
      up was 26 months ([IQR: 2.2-64.8]). The majority of injuries involved motorcycle
      accidents (57.6%), bicycles (30.2%), and other modes of injury (12.7%). The mean
      Glasgow Coma Score (GSC) at the time of presentation was 14.2 (SD +/- 2.4) and
      mean injury severity score (ISS) was 10.2 (SD +/- 7.5). Motorcycle accidents had
      a higher mean ISS compared with other modes of injury ( p  = 0.048). Unhelmeted
      patients were more likely to sustain scalp lacerations ( p  < 0.0001), facial
      bone fractures ( p  = 0.01), scalp hematomas ( p  = 0.041), skull fractures ( p 
      = 0.017), and are more likely to require hospital admission ( p  = 0.0003).
      Unhelmeted patients' hospital length of stay was on average 2 days longer than
      helmeted patients' stay ( p  = 0.0721). Unhelmeted patients were more likely to
      require out-of-home placement than helmeted patients. Among trauma patients,
      helmet use was associated with less scalp lacerations and hematomas, facial bones
      fractures, skull fractures, and need for hospital admission. Adoption of
      legislation and regulations mandating protective helmet use in all states are
      strongly encouraged to minimize the burden of craniofacial injuries among
      unhelmeted patients.

PMID- 28751944
TI  - Complications in Mandibular Midline Distraction.
AB  - Mandibular midline distraction (MMD) is a relatively new surgical technique for
      correction of transverse discrepancies of the mandible. This study assesses the
      amount and burden of complications in MMD. A retrospective cohort study was
      performed on patients who underwent MMD between 2002 and 2014. Patients with
      congenital deformities or a history of radiation therapy in the area of interest
      were excluded. Patient records were obtained and individually assessed for any
      complications. Complications were graded using the Clavien-Dindo classification
      system (CDS). Seventy-three patients were included of which 33 were males and 40
      were females. The mean follow-up was 2.1 years. Twenty-nine patients had minor
      complications, grades I and II. Two patients had a grade IIIa and three patients
      had a grade IIIb complication. Common complications were pressure ulcers,
      dehiscence, and (transient) sensory disturbances of the mental nerve. This study
      shows that although MMD is a relatively safe method, complications can occur.
      Mostly the complications are mild, transient, and manageable without the need for
      any reoperation.

PMID- 28751945
TI  - Injured Anterior Superior Alveolar Nerve Endoscopically Resected within Maxillary
      Sinus.
AB  - Posttraumatic facial pain is due to an injured nerve, most often a branch of the
      trigeminal nerve. While surgical approaches to injuries of the supraorbital,
      supratrochlear, infraorbital, and inferior alveolar nerves have been reported, an
      injury to the anterior superior alveolar nerve (ASAN) has not been reported. An
      algorithm is proposed for the diagnosis of injury to the ASAN versus the
      infraorbital nerve itself. A case is reported in which pain relief was achieved
      by dividing the ASAN within the maxillary sinus, leaving the proximal end exposed
      within the sinus at the level of the orbital floor.

PMID- 28751946
TI  - Concomitant "Ear Bleed and Styloid Fracture": An Unusual Complication of Impacted
      Mandibular Third Molar Removal.
AB  - The removal of impacted mandibular third molar is associated with potential
      complications such as dry socket, paresthesia, uncontrolled socket bleeding,
      angle fracture, etc., which are commonly encountered in dental practice. This
      article presents a peculiar case of "ear bleed" concomitant with "isolated
      styloid" fracture following removal of impacted mandibular third molar, not
      reported in the literature till date. Ear bleed is a bothersome clinical sign
      that requires thorough investigation and prompt treatment because it is
      frequently related to fractures of the skull base. Isolated fracture of the
      styloid process is rare; its diagnosis, impact on adjacent vital structures, and
      treatment protocol are less discussed in maxillofacial literature. The case
      report elucidates the etiopathogenesis of ear bleed and styloid fracture which
      have great clinical implications. The clinical correlation between the two
      entities and dental extraction is discussed in this report to guide a dental
      practitioner in its management.

PMID- 28751947
TI  - Reconstruction of the Cranial Vault Contour Using Tissue Expander and Castor Oil
      Prosthesis.
AB  - Nowadays the reconstruction of craniofacial defects can be performed with
      different kinds of materials, which include the bone and the so-called
      biomaterials, which have the advantage of not needing a surgical site donor.
      Among these materials, great attention is given to polymers. In this large group,
      current attention is focused on the castor oil polymer, since this polymer is
      biocompatible, low cost, and has adequate strength for reconstruction of the
      craniomaxillofacial complex. This study aims to report the use of a prosthetic
      castor oil polymer for reconstruction of extensive defect, caused by a trauma, in
      the temporoparietal region.

PMID- 28751948
TI  - Orbitocerebral Impalement: Case Discussion and Management Algorithm.
AB  - Orbitocerebral impalement by inanimate objects is a relatively uncommon event. If
      orbitocerebral impalement is suspected, management entails prompt referral to a
      trauma facility with neurosurgical, neuroanesthesiological, craniomaxillofacial,
      and ophthalmological expertise. The aim of this report is to describe the unique
      mechanism and perioperative considerations of a remarkable, deep orbitocerebral
      impalement from a walker brake lever through the orbital roof after a fall from
      standing. We discuss clinical vignette, evaluation, anesthetic approach, and
      considerations and review the literature on the epidemiology, pathophysiology,
      surgical and anesthetic management, and prognosis of this traumatic mechanism. We
      also offer a management algorithm that aims to streamline management.

PMID- 28751949
TI  - An Alternative Route for Entrapped Inferior Orbital Nerve in Orbital Floor
      Fracture.
AB  - Orbital floor fractures pose a grave threat for injury to the infraorbital nerve,
      resulting in the patient suffering from a disturbing paraesthesia. It is
      challenging for the operating surgeon to release and secure the entrapped nerve
      with reconstruction of the orbital floor. We present an interesting case of
      orbital floor fracture with entrapped infraorbital nerve, wherein we have
      decompressed the nerve and provided it, a new course.

PMID- 28751950
TI  - Orbital Compartment Syndrome despite Significant Traumatic Expansion of the
      Orbital Cavity.
AB  - Periorbital injury can present with various permutations of bone trauma, soft
      tissue edema, and hematomas that might involve proptosis and restricted motility.
      We report a case of a 32-year-old patient who sustained a traumatic orbital
      compartment syndrome simultaneously with a large, significantly displaced,
      orbital-floor blow-out fracture. Clinical signs consistent with both conditions
      were elicited. The initial management was as for orbital compartment syndrome.
      The clinical diagnosis was confirmed with computed tomographic imaging. This is
      an unusual and unexpected presentation. It would be expected that a hemorrhage
      would self-decompress in the presence of a large fracture. Physicians should be
      aware that such a combination of pathology might arise. Physicians likely to
      encounter periocular trauma should be prepared for its management: urgent lateral
      canthotomy and cantholysis. Differential diagnoses of periocular trauma are
      compared and contrasted.

PMID- 28751951
TI  - Narrow-Bladed "Endo" Sagittal Split Osteotomy Retractor.
AB  - A modification of the Obwegeser sagittal split retractor is presented. It is
      slender while still protecting the soft tissues and is particularly suitable for
      endoscopically assisted surgery.

PMID- 28751952
TI  - In-Office Guided Implant Placement for Prosthetically Driven Implant Surgery.
AB  - Application of surgical stents for implant placement via guided flapless surgery
      is increasing. However, high cost, need for some professional machines, and not
      taking into account the soft-tissue parameters have limited their application. We
      sought to design and introduce a technique named in-office guided implant
      placement (iGIP) to decrease the cost by using available devices in office and
      enhance the applicability of surgical stents. A customized surgical stent was
      fabricated based on prosthetic, soft- and hard-tissue parameters by taking into
      account the amount of available bone (using the computed tomographic [CT] data),
      soft-tissue thickness and contour (using a composite-covered radiographic stent),
      and position of the final crown (by diagnostic cast wax up and marking the final
      crown position with composite). The efficacy of iGIP, in terms of the accuracy of
      the three-dimensional position of the implant placed in the study cast and in
      patient's mouth, was confirmed by direct observation and postoperative CT. The
      iGIP can enhance implant placement in the prosthetically desired position in
      various types of edentulism. Using this technique minimizes the risk of unwanted
      consequences, as the soft-tissue thickness and contour are taken into account
      when fabricating a surgical stent.

PMID- 28751953
TI  - PCSK9 and carbohydrate metabolism: A double-edged sword.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a paramount role in
      the degradation of low-density lipoprotein (LDL) receptors (LDLR) on the hepatic
      cells surface and subsequently affects LDL particles catabolism and LDL
      cholesterol (LDL-c) levels. The anti-PCSK9 monoclonal antibodies lead to
      substantial decrease of LDL-c concentration. PCSK9 (which is also expressed in
      pancreatic delta-cells) can decrease LDLR and subsequently decrease cholesterol
      accumulation in pancreatic beta-cells, which impairs glucose metabolism and
      reduces insulin secretion. Thus, a possible adverse effect of PCSK9 inhibitors on
      carbohydrate metabolism may be expected by this mechanism, which has been
      supported by the mendelian studies results. On the other hand, clinical data have
      suggested a detrimental association of PCSK9 with glucose metabolism. So, the
      inhibition of PCSK9 may be seen as a double-edged sword regarding carbohydrate
      metabolism. Completed clinical trials have not shown a detrimental effect of
      PCSK9 inhibitors on diabetes risk, but their short-term duration does not allow
      definite conclusions.

PMID- 28751954
TI  - Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia.
AB  - Diabetic retinopathy (DR) is the most feared ocular manifestation of diabetes. DR
      is characterized by progressive retinal damage that may eventually result in
      blindness. Clinically, this blindness is caused by progressive damage to the
      retinal microvasculature, which leads to ischemia, retinal swelling, and
      neovascularization. Retinopathy is associated with both type 1 and type 2
      diabetes, with DR being the leading cause of new onset blindness in United States
      adults. Despite this strong association with diabetes, it must be noted that the
      development of retinopathy lesions is multifactorial and may occur in individuals
      without an established history of diabetes. Metabolic syndrome is a
      multifactorial condition of central obesity, hypertriglyceridemia, dyslipidemia,
      hypertension, fasting hyperglycemia, and insulin resistance. Although several
      studies examined the individual components observed in the metabolic syndrome in
      relation to the development of DR, there is conflicting data as to the
      association of the metabolic syndrome with the development of retinopathy lesions
      in non-diabetic subjects. This review will summarize the current literature on
      the evidence of the metabolic syndrome on retinopathy in subjects with and
      without an established history of diabetes. This review will also discuss some of
      the mechanisms through which metabolic syndrome can contribute to the development
      of retinopathy.

PMID- 28751955
TI  - PTPN22 and islet-specific autoimmunity: What have the mouse models taught us?
AB  - An allelic variant of the protein tyrosin phosphatase non-receptor 22 (PTPN22)
      gene, PTPN22 R620W, constitutes the strongest non-HLA genetic risk factor for the
      development of type 1 diabetes (T1D). A number of studies using mouse models have
      addressed how PTPN22 predisposes to T1D. PTPN22 downmodulation, overexpression or
      expression of the variant gene in genetically manipulated mice has generated
      controversial results. These discrepancies probably derive from the fact that
      PTPN22 has differential effects on innate and adaptive immune responses.
      Moreover, the effects of PTPN22 are dependent on other genetic variables. Here we
      discuss these findings and try to explain the discrepancies. Exploring the
      mechanism by which PTPN22 contributes to islet-specific autoimmunity could help
      us understand its role in T1D pathogenesis and exploit it as a potential
      therapeutic target to prevent the disease.

PMID- 28751956
TI  - Saponins as adipokines modulator: A possible therapeutic intervention for type 2
      diabetes.
AB  - Development of type 2 diabetes has been linked to beta-cell failure coupled with
      insulin resistance and obesity. Adipose tissue, known as the fat store, secretes
      a number of hormones and proteins collectively termed adipokines some of which
      regulate insulin sensitivity. Dysregulation in the secretion of adipokines has
      been linked to insulin resistance and type 2 diabetes. In this review, we
      summarized evidence of the role of adipokines with focus on leptin, adiponectin,
      adipsin, visfatin and apelin in the pathogenesis of type 2 diabetes and discussed
      the potential of saponins to modify the ill-regulated adipokines secretions,
      which could promote the use of this class of phytochemicals as potential
      antidiabetics agents.

PMID- 28751957
TI  - Vitamin D levels in subjects with or without chronic kidney disease among
      Veterans with diabetes in North East United States.
AB  - AIM: To evaluate the prevalence of vitamin D deficiency and its relation to
      diabetes and kidney disease in Veterans residing in the North East United States
      (VISN 2). METHODS: In this retrospective study, we used data from the
      computerized patient record system at Stratton Veterans Administration Medical
      Center at Albany, NY (VHA) for those patients who had 25-hydroxyvitamin D levels
      and 1,25 (OH) vitamin D levels measured between 2007 and 2010. We collected
      demographic information including age, sex, body mass index and race; clinical
      data including diabetes, hypertension and CAD; and laboratory data including
      calcium, creatinine and parathyroid hormone (PTH) (intact). Vitamin D deficiency
      is defined as a serum 25-hydroxyvitamin D level of less than 20 ng/mL (50
      nmol/L), and insufficiency is defined as a serum 25-hydroxyvitamin D level of 20
      to 30 ng/mL (50 to 75 nmol/L). RESULTS: Data was available for approximately
      68000 subjects. We identified 64144 subjects for analysis after exclusion of
      duplicates. Among them, 27098 had diabetes. The mean age of subjects with
      diabetes was 68 +/- 11 with a mean body mass index (BMI) of 32 +/- 7 and duration
      of diabetes of 5.6 +/- 3.2 years. The mean 25 (OH) vitamin D level among subjects
      with diabetes was 27 +/- 11.6. There was no significant difference in 25 (OH)
      vitamin D levels between subjects with diabetes and glomerular filtration rate (e
      GFR) < 60 compared to those with e-GFR >= 60. As expected, subjects with e-GFR <
      60 had significantly lower 1,25 (OH) vitamin D levels and significantly elevated
      PTH-intact. Of the 64144 subjects, 580 had end-stage renal disease. Of those, 407
      had diabetes and 173 did not. Vitamin D levels in both groups were in the
      insufficiency range and there was no significant difference irrespective of
      presence or absence of diabetes. Subjects with vitamin D levels less than 20
      ng/mL had a higher BMI and elevated PTH, and higher HbA1C levels compared to
      those with vitamin D levels more than 20 ng/mL. CONCLUSION: We conclude that we
      need to keep a close eye on vitamin D levels in subjects with mild chronic kidney
      disease as well as those with moderate control of diabetes.

PMID- 28751958
TI  - Type 2 diabetes in a Senegalese rural area.
AB  - AIM: To estimate the prevalence of diabetes in the rural population of Tessekere
      (Senegal) and investigate associated risk factors. METHODS: Data from a 2015
      survey of 500 individuals age 20 and over representative of the population of the
      municipality of Tessekere were used. Sociodemographic characteristics, health
      related variables, capillary whole blood glucose, and weight and height
      measurements of individuals were collected during face-to-face interviews.
      Statistical analyses used were bivariate tests and binary logistic regressions.
      RESULTS: The percentage of individuals having impaired fasting glucose (IFG) is
      6.6%. Those with fasting blood glucose (FBG) levels >= 126 mg/dL and/or currently
      being treated for diabetes is 4.2%. Only mean body mass index (BMI) is
      significantly higher among diabetic individuals and among those having FBG levels
      >= 110 mg/dL. After adjustment for sex, age, educational level, BMI and
      hypertension, only BMI is associated with diabetes. CONCLUSION: Prevalence of
      diabetes and IFG in our study correspond to the high range of rural sub-Saharan
      Africa prevalence. Diabetes is thus becoming a pressing public health concern,
      even in rural areas. But the risk factors identified in Tessekere suggest that
      the diabetes epidemic is still in the early stages, such that concerted action
      would make it possible to contain the devastating impact of this chronic
      condition.

PMID- 28751959
TI  - Quality of sleep and its determinants among people with type 2 diabetes mellitus
      in Northwest of Iran.
AB  - AIM: To examine sleep quality and its determinants among people with type 2
      diabetes mellitus (T2DM). METHODS: This is a cross-sectional study conducted
      among diabetic patients referring to Ardabil diabetes clinic in Northwest of
      Iran. Information on sleep quality was collected using Pittsburg Sleep Quality
      Index (PSQI). A questionnaire was used to collect data on sociodemographic
      lifestyle factors and psychological distress. This questionnaire was completed
      through an interview, and clinical information was extracted from patient's
      record. Data analysis was done using SPSS software version 23 and univariate and
      multivariate analyses. RESULTS: Study participants consist of 256 people with
      T2DM the majority of whom were women (70%), and mean age of participants was
      54.06 +/- 9.09. The mean of total score of PSQI was 5.56 +/- 3.34. Relative to
      younger age group, the middle-aged people with T2DM were twice more likely to be
      poor sleeper; the adjusted OR was 2.03 (95%CI: 1.01-4.08); and those with longer
      duration of diabetes were about 1.8 times more likely to report poor quality of
      sleep (ORadj = 1.77, 95%CI: 0.98-3.13). Participants with cholesterol level >=
      240 mg/dL were about twice more likely to be poor sleeper (ORadj = 1.99, 95%CI:
      1.01-3.94). The odds of being poor sleeper increased as the level of distress
      increased (1.84-4.09). CONCLUSION: As indicated by the results of the present
      study, some factors including age, duration of disease, psychological distress
      and high level of cholesterol were independently associated with poor sleep
      quality.

PMID- 28751960
TI  - Are body mass index and waist circumference significant predictors of diabetes
      and prediabetes risk: Results from a population based cohort study.
AB  - AIM: To determine the predictive role of body mass index (BMI) and waist
      circumference (WC) for diabetes and prediabetes risk in future in total sample as
      well as in men and women separately. METHODS: In a population based cohort study,
      1765 with mean +/- SD age: 42.32 +/- 6.18 healthy participants were followed up
      from 2003 till 2013 (n = 960). Anthropometric and biochemical measures of
      participants were evaluated regularly during the follow up period. BMI and WC
      measures at baseline and diabetes and prediabetes status of participants at 2013
      were determined. Multivariable logistic regression analysis was used for
      determining the risk of diabetes and prediabetes considering important potential
      confounding variables. Receiver operating characteristic curve analysis was
      conducted to determine the best cut of values of BMI and WC for diabetes and
      prediabetes. RESULTS: At 2013, among participants who had complete data, 45 and
      307 people were diabetic and prediabetic, respectively. In final fully adjusted
      model, BMI value was a significant predictor of diabetes (RR = 1.39, 95%CI: 1.06
      1.82 and AUC = 0.68, 95%CI: 0.59-0.75; P < 0.001) however not a significant risk
      factor for prediabetes. Also, WC was a significant predictor for diabetes (RR =
      1.2, 95%CI: 1.05-1.38 and AUC = 0.67, 95%CI: 0.6-0.75) but not significant risk
      factor for prediabetes. Similar results were observed in both genders.
      CONCLUSION: General and abdominal obesity are significant risk factors for
      diabetes in future.

PMID- 28751961
TI  - Effect of bariatric surgery on adiposity and metabolic profiles: A prospective
      cohort study in Middle-Eastern patients.
AB  - AIM: To investigate changes in adiposity and cardio-metabolic risk profile
      following Roux-en-Y gastric bypass in patients of Middle Eastern ethnicity with
      severe obesity. METHODS: This prospective cohort study involved 92 patients who
      met the indications of bariatric surgery. Post-procedure markers of obesity and
      cardiometabolic profile were monitored regularly for a year. RESULTS: Mean body
      mass index decreased by 29.5% from 41.9 to 29.5 kg/m2 between baseline and 12-mo
      follow-up, while mean fat mass decreased by 45.9% from 64.2 kg to 34.7 kg. An
      improvement was also observed in the gluco-metabolic profile with both fasting
      glucose and HbA1c substantially decreasing (P < 0.001). CONCLUSION: The present
      study shows the short to medium term (1 year) health benefits of bariatric
      surgery for patients of Middle Eastern ethnicity.

PMID- 28751962
TI  - Autologous bone marrow derived stem cell therapy in patients with type 2 diabetes
      mellitus - defining adequate administration methods.
AB  - AIM: To carry out randomized trial for evaluating effects of autologous bone
      marrow derived stem cell therapy (ABMSCT) through different routes. METHODS: Bone
      marrow aspirate was taken from the iliac crest of patients. Bone marrow
      mononuclear cells were separated and purified using centrifugation. These cells
      were then infused in a total of 21 patients comprising three groups of 7 patients
      each. Cells were infused into the superior pancreaticoduodenal artery (Group I),
      splenic artery (Group II) and through the peripheral intravenous route (Group
      III). Another group of 7 patients acted as controls and a sham procedure was
      carried out on them (Group IV). The cells were labelled with the PET tracer F18
      FDG to see their homing and in vivo distribution. Data for clinical outcome was
      expressed as mean +/- SE. All other data was expressed as mean +/- SD. Baseline
      and post treatment data was compared at the end of six months, using paired t
      test. Cases and controls data were analyzed using independent t-test. A
      probability (P) value of < 0.05 was regarded as statistically significant.
      Measures of clinical outcome were taken as the change or improvement in the
      following parameters: (1) C-peptide assay; (2) HOMA-IR and HOMA-B; (3) reduction
      in Insulin dose; subjects who showed reduction of insulin requirement of more
      than 50% from baseline requirement were regarded as responders; and (4) reduction
      in HbA1c. RESULTS: All the patients, after being advised for healthy lifestyle
      changes, were evaluated at periodical intervals and at the end of 6 mo. The
      changes in body weight, body mass index, waist circumference and percentage of
      body fat in all groups were not significantly different at the end of this
      period. The results of intra-group comparison before and after ABMSCT at the end
      of six months duration was as follows: (1) the area under C-peptide response
      curve was increased at the end of 6 mo however the difference remained
      statistically non-significant (P values for fasting C-peptide were 0.973, 0.103,
      0.263 and 0.287 respectively and the P values for stimulated C-peptide were
      0.989, 0.395, 0.325 and 0.408 respectively for groups I to IV); (2) the Insulin
      sensitivity indices of HOMA IR and HOMA B also did not show any significant
      differences (P values for HOMA IR were 0.368, 0.223, 0.918 and 0.895 respectively
      and P values for HOMA B were 0.183, 0.664, 0.206 and 0.618 respectively for
      groups I to IV); (3) Group Ishowed a significant reduction in Insulin dose
      requirement (P < 0.01). Group II patients also achieved a significant reduction
      in Insulin dosages (P = 0.01). The Group I and Group II patients together
      constituted the targeted group wherein the feeding arteries to pancreas were used
      for infusing stem cells. Group III, which was the intravenous group, showed a non
      significant reduction in Insulin dose requirement (P = 0.137). Group IV patients
      which comprised the control arm also showed a significant reduction in Insulin
      dosages at the end of six months (P < 0.05); and (4) there was a non-significant
      change in the Hb A1c levels at the end of 6 mo across all groups (P = 0.355, P =
      0.351, P = 0.999 and P = 0.408 respectively for groups I to IV). CONCLUSION:
      Targeted route showed a significant reduction in Insulin requirement at the end
      of six months of study period whereas the intravenous group failed to show
      reduction.

PMID- 28751963
TI  - L-arginine supplementation and risk factors of cardiovascular diseases in healthy
      men: a double-blind randomized clinical trial.
AB  - Context: The effect of L-arginine on risk factors of cardiovascular diseases
      (CVD) has mostly focused on western countries. Since cardiovascular diseases is
      the second cause of death in Iran and, as far as we are aware, there have been no
      studies about the effect of L-arginine on CVD risk factors, the aim of this trial
      was to assess the effects of L-arginine supplementation on CVD risk factors in
      healthy men. Objective: The purpose of this study was to evaluate the effect of
      low-dose L-arginine supplementation on CVD risk factors (lipid profile, blood
      sugar and blood pressure) in Iranian healthy men. Design, setting, participants:
      We conducted a double-blind randomized controlled trial in 56 patients selected
      from sport clubs at the Isfahan University of Medical Science between November
      2013 and December 2013. Interventions: Healthy men received L-arginine
      supplementation (2000 mg daily) in the intervention group or placebo (2000 mg
      maltodextrin daily) in the control group for 45 days. Main outcome measure: The
      primary outcome measures were we measured the levels of fasting blood sugar,
      blood pressure and lipid profile including triglyceride (TG), cholesterol, LDL
      and HDL in healthy subjects. It was hypothesized that these measures would be
      significantly improved in those receiving L-arginine supplementation. at the
      beginning and end of the study. Results: In this trial, we had complete data for
      52 healthy participants with mean age of 20.85+/-4.29 years. At the end of study,
      fasting blood sugar (P=0.001) and lipid profile (triglycerideTG (P<0.001),
      cholesterol (P<0.001), LDL (P=0.04), HDL (P=0.015)) decreased in the L-arginine
      group but we found no significant change in the placebo group. In addition, the
      reduction of fasting blood sugar and lipid profile in L-arginine was significant
      compared with placebo group. No significant changes were found about systolic
      (P=0.81) and diastolic blood pressure either in L-arginine or placebo group.
      (P=0.532). Conclusion: The use of L-arginine significantly improved outcomes
      compared to placebo.

PMID- 28751964
TI  - Method-centered digital communities on protocols.io for fast-paced scientific
      innovation.
AB  - The Internet has enabled online social interaction for scientists that previously
      happened only in physical meetings and conferences. Yet despite these innovations
      in communication, dissemination of methods is often relegated to the slow process
      of academic publishing. Further, these methods remain static, with subsequent
      advances published elsewhere and unlinked. For communities undergoing fast-paced
      innovation, researchers need new capabilities to share, obtain feedback, and
      publish methods at the forefront of scientific development. For example, a
      renaissance in virology is now underway given the new metagenomic methods to
      sequence viral DNA directly from an environment. Metagenomics makes it possible
      to "see" natural viral communities that could not be previously studied through
      culturing methods. Yet, the knowledge of specialized techniques for the
      production and analysis of viral metagenomes remains in a subset of labs.  This
      problem is common to any community using and developing emerging technologies and
      techniques. We developed new capabilities to create virtual communities in
      protocols.io, an open access platform, for disseminating protocols and knowledge
      at the forefront of scientific development. To demonstrate these capabilities, we
      present a virology community forum called VERVENet. These new features allow
      virology researchers to share protocols and their annotations and optimizations,
      connect with the broader virtual community to share knowledge, job postings,
      conference announcements through a common online forum, and discover the current
      literature through personalized recommendations to promote discussion of cutting
      edge research. Virtual communities in protocols.io enhance a researcher's ability
      to: discuss and share protocols, connect with fellow community members, and learn
      about new and innovative research in the field.  The web-based software for
      developing virtual communities is free to use on protocols.io. Data are available
      through public APIs at protocols.io.

PMID- 28751965
TI  - Four simple recommendations to encourage best practices in research software.
AB  - Scientific research relies on computer software, yet software is not always
      developed following practices that ensure its quality and sustainability. This
      manuscript does not aim to propose new software development best practices, but
      rather to provide simple recommendations that encourage the adoption of existing
      best practices. Software development best practices promote better quality
      software, and better quality software improves the reproducibility and
      reusability of research. These recommendations are designed around Open Source
      values, and provide practical suggestions that contribute to making research
      software and its source code more discoverable, reusable and transparent. This
      manuscript is aimed at developers, but also at organisations, projects, journals
      and funders that can increase the quality and sustainability of research software
      by encouraging the adoption of these recommendations.

PMID- 28751966
TI  - Resistance mechanisms to drug therapy in breast cancer and other solid tumors: An
      opinion.
AB  - Cancer is an important contributor to mortality worldwide. Breast cancer is the
      most common solid tumor in women. Despite numerous drug combinations and
      regimens, all patients with advanced breast cancer, similarly to other solid
      tumors, inevitably develop resistance to treatment. Identified mechanisms of
      resistance could be classified into intra- and extracellular mechanisms.
      Intracellular mechanisms include drug metabolism and efflux, target modulations
      and damage restoration. Extracellular mechanisms might be attributed to the
      crosstalk between tumor cells and environmental factors. However, current
      knowledge concerning resistance mechanisms cannot completely explain the
      phenomenon of multi-drug resistance, which occurs in the vast majority of
      patients treated with chemotherapy. In this opinion article, we investigate the
      role of these factors in the development of drug-resistance.

PMID- 28751967
TI  - Protein sites with more coevolutionary connections tend to evolve slower, while
      more variable protein families acquire higher coevolutionary connections.
AB  - Background: Correlated mutation or coevolution of positions in a protein is
      tightly linked with the protein's respective evolutionary rate. It is essential
      to investigate the intricate relationship between the extent of coevolution and
      the evolutionary variability exerted at individual protein sites, as well as the
      whole protein. Methods: In this study, we have used a reliable set of
      coevolutionary connections (sites within 10A spatial distance) and investigated
      their correlation with the evolutionary diversity within the respective protein
      sites. Results: Based on our observations, we propose an interesting hypothesis
      that higher numbers of coevolutionary connections are associated with lesser
      evolutionary variable protein sites, while higher numbers of the coevolutionary
      connections can be observed for a protein family that has higher evolutionary
      variability. Our findings also indicate that highly coevolved sites located in a
      solvent accessible state tend to be less evolutionary variable. This relationship
      reverts at the whole protein level where cytoplasmic and extracellular proteins
      show moderately higher anti-correlation between the number of coevolutionary
      connections and the average evolutionary conservation of the whole protein.
      Conclusions: Observations and hypothesis presented in this study provide
      intriguing insights towards understanding the critical relationship between
      coevolutionary and evolutionary changes observed within proteins. Our
      observations encourage further investigation to find out the reasons behind
      subtle variations in the relationship between coevolutionary connectivity and
      evolutionary diversity for proteins located at various cellular localizations
      and/or involved in different molecular-biological functions.

PMID- 28751968
TI  - Lumboperitoneal shunt insertion without fluoroscopy guidance: Accuracy of
      placement in a series of 107 procedures.
AB  - Background: Lumboperitoneal (LP) shunts were the mainstay of cerebrospinal fluid
      diversion therapy for idiopathic intracranial hypertension (IIH). The
      traditionally cited advantage of LP shunts over ventriculoperitoneal (VP) shunts
      is the ease of insertion in IIH. This needs to be placed at the level of L3/4 to
      be below the level of the spinal cord. The objective of this study was to analyse
      the position of LP shunts inserted without portable fluoroscopy guidance. 
      Methods: A retrospective analysis of radiology was performed for patients who
      underwent lumboperitoneal shunts between 2006 and 2016 at the National Hospital
      for Neurology and Neurosurgery. Patients who had insertion of a LP shunt without
      fluoroscopy guidance were selected.  Patients without post-procedural imaging
      were excluded. A retrospective analysis of the clinical notes was also performed.
      Results: Between 2006 and 2016, 163 lumboperitoneal shunts were inserted in 105
      patients. A total of 56 cases were excluded due to lack of post-procedural
      imaging; therefore, 107 post-procedural x-rays were reviewed. In 17 (15.8%) cases
      the proximal end of the LP shunt was placed at L1/L2 level or above. 
      Conclusions: Insertion of LP shunts without portable fluoroscopy guidance gives a
      15.8% risk of incorrect positioning of the proximal end of the catheter. We
      suggest that x-ray is recommended to avoid incorrect level placement. Further
      investigation could be carried out with a control group with fluoroscopy against
      patients without.

PMID- 28751969
TI  - valr: Reproducible genome interval analysis in R.
AB  - New tools for reproducible exploratory data analysis of large datasets are
      important to address the rising size and complexity of genomic data. We developed
      the valr R package to enable flexible and efficient genomic interval analysis.
      valr leverages new tools available in the "tidyverse", including dplyr.
      Benchmarks of valr show it performs similar to BEDtools and can be used for
      interactive analyses and incorporated into existing analysis pipelines.

PMID- 28751970
TI  - Service evaluation of the implementation of a digitally-enabled care pathway for
      the recognition and management of acute kidney injury.
AB  - Acute Kidney Injury (AKI), an abrupt deterioration in kidney function, is defined
      by changes in urine output or serum creatinine. AKI is common (affecting up to
      20% of acute hospital admissions in the United Kingdom), associated with
      significant morbidity and mortality, and expensive (excess costs to the National
      Health Service in England alone may exceed L1 billion per year). NHS England has
      mandated the implementation of an automated algorithm to detect AKI based on
      changes in serum creatinine, and to alert clinicians. It is uncertain, however,
      whether 'alerting' alone improves care quality. We have thus developed a
      digitally-enabled care pathway as a clinical service to inpatients in the Royal
      Free Hospital (RFH), a large London hospital. This pathway incorporates a mobile
      software application - the "Streams-AKI" app, developed by DeepMind Health - that
      applies the NHS AKI algorithm to routinely collected serum creatinine data in
      hospital inpatients. Streams-AKI alerts clinicians to potential AKI cases,
      furnishing them with a trend view of kidney function alongside other relevant
      data, in real-time, on a mobile device. A clinical response team comprising
      nephrologists and critical care nurses responds to these AKI alerts by reviewing
      individual patients and administering interventions according to existing
      clinical practice guidelines. We propose a mixed methods service evaluation of
      the implementation of this care pathway. This evaluation will assess how the care
      pathway meets the health and care needs of service users (RFH inpatients), in
      terms of clinical outcome, processes of care, and NHS costs. It will also seek to
      assess acceptance of the pathway by members of the response team and wider
      hospital community. All analyses will be undertaken by the service evaluation
      team from UCL (Department of Applied Health Research) and St George's, University
      of London (Population Health Research Institute).

PMID- 28751971
TI  - Recent advances in understanding eosinophil biology.
AB  - With the advent of novel therapies targeting eosinophils, there has been renewed
      interest in understanding the basic biology of this unique cell. In this context,
      murine models and human studies have continued to highlight the role of the
      eosinophil in homeostatic functions and immunoregulation. This review will focus
      on recent advances in our understanding of eosinophil biology that are likely to
      have important consequences on the development and consequences of eosinophil
      targeted therapies. Given the breadth of the topic, the discussion will be
      limited to three areas of interest: the eosinophil life cycle, eosinophil
      heterogeneity, and mechanisms of cell-cell communication.

PMID- 28751972
TI  - Chronic urticaria: a focus on pathogenesis.
AB  - Chronic urticaria is a spontaneous or inducible group of diseases characterized
      by the occurrence of wheals (and, in about half of cases, angioedema) for more
      than 6 weeks. These are rather frequent conditions that may severely affect
      patients' quality of life and sometimes represent a challenge for doctors as
      well. The causes of chronic urticaria are still poorly defined, although there is
      growing evidence that different biologic systems including immunity,
      inflammation, and coagulation may take part in the pathomechanism eventually
      leading to mast cell and basophil degranulation and hence to wheal formation.
      This review will discuss the main findings that are (slowly) shedding light on
      the pathogenesis of this disorder.

PMID- 28751974
TI  - Coronary CT angiography in acute chest pain.
AB  - Coronary computed tomographic angiography has become a reliable diagnostic tool
      in the evaluation of patients with chest pain. Studies have shown this modality
      to be accurate and safe when compared with conventional methods of assessing
      patients with chest pain. We review the recent developments with coronary
      computed tomographic angiography and devote particular attention toward its
      application to triage patients in the emergency department.

PMID- 28751973
TI  - Progress toward an integrated understanding of Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      after Alzheimer's disease, affecting over 10 million individuals worldwide. While
      numerous effective symptomatic treatments are currently available, no curative or
      disease-modifying therapies exist. An integrated, comprehensive understanding of
      PD pathogenic mechanisms will likely address this unmet clinical need. Here, we
      highlight recent progress in PD research with an emphasis on promising
      translational findings, including (i) advances in our understanding of disease
      susceptibility, (ii) improved knowledge of cellular dysfunction, and (iii)
      insights into mechanisms of spread and propagation of PD pathology. We emphasize
      connections between these previously disparate strands of PD research and the
      development of an emerging systems-level understanding that will enable the next
      generation of PD therapeutics.

PMID- 28751975
TI  - Comparison between CT Net enhancement and PET/CT SUV for N staging of gastric
      cancer: A case series.
AB  - BACKGROUND: The therapeutic approach of gastric cancer strictly depends on TNM
      staging mainly provided by CT and PET/CT. However, the lymph node size criterion
      as detected by MDCT causes a poor differential diagnosis between reactive and
      metastatic enlarged lymph nodes with low specificity values. Our study aims to
      compare 320-row CT Net enhancement and fluorine-18 fluoro-2-deoxy-d-glucose
      positron emission tomography/computed tomography (F-FDG PET/CT) SUV for N staging
      of gastric cancer. MATERIALS AND METHODS: 45 patients with histologically proven
      gastric cancer underwent CT and F-FDG PET/CT. Two radiologists in consensus
      evaluated all images and calculated the CT Net enhancement and F-FDG PET/CT SUV
      for N staging, having the histological findings as the reference standard. CT and
      F-FDG PET/CT sensitivity, specificity, diagnostic accuracy, positive and negative
      predictive values (PPV and NPV) were evaluated and compared by using the Mc Nemar
      test. RESULTS: The histological examination revealed nodal metastases in 29/45
      cases (64%). CT Net enhancement obtained sensitivity, specificity, accuracy, PPV
      and NPV of 90%, 81%, 87%, 90% and 81%, respectively. F-FDG PET/CT SUV obtained
      sensitivity, specificity, accuracy, PPV and NPV of 66%, 88%, 73%, 90% and 58%,
      respectively. No statistically significant difference between the two imaging
      modalities was found (p = 0.1). CONCLUSION: CT Net enhancement represents an
      accurate tool for N staging of gastric cancer and could be considered as the CT
      corresponding quantitative parameter of F-FDG PET/CT SUV. It could be applied in
      the clinical practice for differentiating reactive lymph nodes from metastatic
      ones improving accuracy and specificity of CT.

PMID- 28751976
TI  - Manganese transporter Slc39a14 deficiency revealed its key role in maintaining
      manganese homeostasis in mice.
AB  - SLC39A14 (also known as ZIP14), a member of the SLC39A transmembrane metal
      transporter family, has been reported to mediate the cellular uptake of iron and
      zinc. Recently, however, mutations in the SLC39A14 gene have been linked to
      manganese (Mn) accumulation in the brain and childhood-onset parkinsonism
      dystonia. It has therefore been suggested that SLC39A14 deficiency impairs
      hepatic Mn uptake and biliary excretion, resulting in the accumulation of Mn in
      the circulation and brain. To test this hypothesis, we generated and
      characterized global Slc39a14-knockout (Slc39a14-/- ) mice and hepatocyte
      specific Slc39a14-knockout (Slc39a14fl/fl;Alb-Cre+ ) mice. Slc39a14-/- mice
      develop markedly increased Mn concentrations in the brain and several
      extrahepatic tissues, as well as motor deficits that can be rescued by treatment
      with the metal chelator Na2CaEDTA. In contrast, Slc39a14fl/fl;Alb-Cre+ mice do
      not accumulate Mn in the brain or other extrahepatic tissues and do not develop
      motor deficits, indicating that the loss of Slc39a14 expression selectively in
      hepatocytes is not sufficient to cause Mn accumulation. Interestingly,
      Slc39a14fl/fl;Alb-Cre+ mice fed a high Mn diet have increased Mn levels in the
      serum, brain and pancreas, but not in the liver. Taken together, our results
      indicate that Slc39a14-/- mice develop brain Mn accumulation and motor deficits
      that cannot be explained by a loss of Slc39a14 expression in hepatocytes. These
      findings provide insight into the physiological role that SLC39A14 has in
      maintaining Mn homeostasis. Our tissue-specific Slc39a14-knockout mouse model can
      serve as a valuable tool for further dissecting the organ-specific role of
      SLC39A14 in regulating the body's susceptibility to Mn toxicity.

PMID- 28751977
TI  - Sheila Jennett and Ludwig Guttmann.

PMID- 28751978
TI  - Intracerebral haemorrhage following uncontrolled autonomic dysreflexia post
      suprapubic catheter placement surgery.
AB  - INTRODUCTION: We describe a case of intracerebral haemorrhage (ICH) following
      uncontrolled episodes of autonomic dysreflexia (AD) within 24 h of a minor
      urological procedure. CASE PRESENTATION: A 33-year-old active paraplegic patient
      T1 Association Impairment Scale A underwent an elective suprapubic catheter (SPC)
      placement for bladder management. The surgery was done under general anaesthesia
      and was uneventful. Four hours after surgery, he developed haematuria and
      multiple blood clots in the urine, which eventually caused blockage of the SPC
      and resulted in symptomatic AD. The clots and blockage persisted, which continued
      to trigger repeated episodes of increased blood pressure (BP) and AD. Despite
      medical treatment with sublingual nitrate to lower the increased BP, the patient
      subsequently developed massive left ICH presenting with right upper limb
      weakness, facial asymmetry and inability to speak. He continued to have
      fluctuating BP measurements for 11 days post event with severe hypertensive and
      hypotensive episodes. This presented a challenge in the BP management as well as
      post-ICH management. He underwent an intensive neurorehabilitation programme as
      soon as the BP had stabilized. DISCUSSION: Severe neurological complications of
      AD are rare. In this case report, we highlight the importance of close monitoring
      of BP and AD symptoms after an SPC procedure, the challenges in BP management and
      the subsequent importance of an early rehabilitation programme after ICH
      secondary to uncontrolled AD.

PMID- 28751979
TI  - Application of Rho Kinase Inhibitors for the Treatment of Corneal Endothelial
      Diseases.
AB  - ROCK (Rho kinase) signaling regulates a wide spectrum of fundamental cellular
      events and is involved in a variety of pathological conditions. It has therefore
      attracted research interest as a potential therapeutic target for combating
      various diseases. We showed that inhibition of ROCK enhances cell proliferation,
      promotes cell adhesion onto a substrate, and suppresses apoptosis of corneal
      endothelial cells (CECs). In addition, we reported that a ROCK inhibitor enhances
      wound healing in the corneal endothelium in animal models and in pilot clinical
      research. We also demonstrated the usefulness of a ROCK inhibitor as an adjunct
      drug in tissue engineering therapy as it enhances the engraftment of CECs onto
      recipient corneas. In 2013, we initiated a clinical trial to test the
      effectiveness of injection of cultured human CECs into the anterior chamber of
      patients with corneal endothelial decompensation. This paper reviews the
      accumulating evidence supporting the potency of ROCK inhibitors in clinical use,
      both as eye drops and as adjunct drugs in cell-based therapies, for the treatment
      of corneal endothelial decompensation.

PMID- 28751980
TI  - A Meta-Analysis of Choroidal Thickness Changes in Unilateral Amblyopia.
AB  - PURPOSE: To date, the topic of amblyopic changes remains controversial.
      Therefore, a systematic review and meta-analysis were carried out to evaluate
      choroidal changes in unilateral amblyopia. METHODS: Major literature databases
      were searched for amblyopia-relevant studies. Using enhanced depth imaging
      optical coherence tomography (EDI-OCT), the primary outcome parameters examined
      were subfoveal choroidal thickness (SFCT) and different choroidal thickness (CT)
      positions. Efficacy estimates were evaluated by weighted mean difference (WMD)
      and 95% confidence interval (CI) for choroidal-associated changes. We performed
      subgroup analysis and metaregression analysis to examine potential sources of
      heterogeneity. RESULTS: Eleven cross-sectional studies that included a total of
      768 participants were identified. The amblyopic eye SFCT was thicker than that of
      the fellow and control (normal) eyes (WMDamblyopia versus fellow = 49.24, 95% CI
      of 30.22 to 68.27, p < 0.001; WMDamblyopia versus control = 54.51, 95% CI of
      32.17 to 76.85, p < 0.001). There were no differences between the fellow and
      control eyes (WMD = 13.81, 95% CI of 1.16 to 28.77, p = 0.071). Subgroup and
      metaregression analyses indicated that the OCT type was the main source of
      heterogeneity. CONCLUSIONS: The CT in the amblyopic eyes was thicker than that in
      the fellow and control eyes.

PMID- 28751981
TI  - Characterization of Soft Contact Lens Fitting Using Ultra-Long Scan Depth Optical
      Coherence Tomography.
AB  - OBJECTIVES: To evaluate the centration and movement of soft contact lenses and to
      verify the repeatability of two repeated measurements of the lens centration and
      movement using ultra-long scan depth optical coherence tomography (UL-OCT).
      METHODS: A 1-day Acuvue(r) DefineTM lens was tested on both eyes of 10 subjects
      (5 males and 5 females; mean age, 31.6 years). The centration and blink-induced
      movement of the contact lens were measured using UL-OCT at 5 min and 30 min after
      insertion. The measurements were repeated once at each checkpoint. RESULTS: Good
      repeatability was found in the lens centration and movement between the two
      repeated measurements at either checkpoint. The values of the lens movement were
      0.457 +/- 0.248 mm and 0.402 +/- 0.229 mm at 5 min and decreased to 0.197 +/-
      0.065 mm and 0.211 +/- 0.110 mm at 30 min after insertion for the right and left
      eyes, respectively (P < 0.05). CONCLUSIONS: The custom-built UL-OCT presented
      good repeatability of centration and movement in Define lenses at 5 min and 30
      min after insertion. Most of the lenses were centered temporal and inferior to
      the cornea during the first 30 min wearing period. Compared with 5 min after
      insertion, the lens was centered better and exhibited less movement at 30 min.

PMID- 28751982
TI  - Clinical Features and Treatments of Syphilitic Uveitis: A Systematic Review and
      Meta-Analysis.
AB  - PURPOSE: To investigate the clinical features and efficacies of treatments for
      syphilitic uveitis. METHODS: PubMed was searched for studies of syphilitic
      uveitis published between January 1990 and October 2016. The clinical features
      were summarized and appraised. The pooled success rate was defined as an improved
      or maintained final visual acuity and was calculated with 95% confidence
      intervals (CIs). Heterogeneity, subgroup analysis, sensitivity analysis, and
      publication bias were assessed. RESULTS: Thirty-two studies involving 670
      patients were analyzed. The most common type of syphilitic uveitis was
      papillitis. The pooled success rate was 0.91 (95% CI 0.84-0.97) for antibacterial
      agents alone (15 studies, 286 patients); 0.95 (95% CI 0.91-0.98) for
      antibacterial agents and systemic corticosteroids combined (11 studies, 245
      patients); and 0.91 (95% CI 0.80-0.98) for antibacterial agents, systemic
      corticosteroids, and other immunosuppressants combined (3 studies, 73 patients).
      Subgroup analyses revealed no correlations of the efficacy of antibacterial agent
      monotherapy with study characteristics, such as human immunodeficiency virus
      coinfection status. CONCLUSIONS: This systematic review and meta-analysis
      revealed the efficacy of antibacterial agents for treating syphilitic uveitis.
      Coadministration of systemic corticosteroids or immunosuppressants did not elicit
      further improvements in the clinical outcomes of antibacterial agents.

PMID- 28751983
TI  - Advances in Vitreoretinal Interface Disorders.

PMID- 28751984
TI  - Corneal Backscatters as an Objective Index for Assessing Fuchs' Endothelial
      Corneal Dystrophy: A Pilot Study.
AB  - PURPOSE: To provide an objective, quantitative approach for monitoring Fuchs'
      endothelial corneal dystrophy (FECD), with Scheimpflug imaging. DESIGN: This is a
      retrospective case-control pilot study. METHODS: The study group consisted of 53
      eyes in 27 patients diagnosed with FECD, with normal subjects paired as control.
      Main outcome measures were corneal thickness, morphological patterns on
      densitograms, and indices of corneal density including the average area density
      (mean AD) and the average ratio of Descemet's membrane density versus area
      density (DM/AD) in Pentacam Scheimpflug images. RESULTS: There were no
      significant differences in age and corneal thickness between FECD and normal
      groups. Morphologically, hanging-hammock patterns were noted on the densitograms
      of FECD patients, which were different from the high-back chair patterns in
      normal subjects. Quantitatively, mean AD and DM/AD were both elevated in FECD
      patients as compared with normal subjects (P = 0.01 and 0.025, resp.). In
      addition, FECD patients with corneal edema had significantly higher mean AD (P =
      0.018) than those without corneal edema. CONCLUSIONS: This pilot study shows that
      Pentacam system provides an objective, quantitative way to approach FECD corneas.
      It can assist ophthalmologists in detecting the early change and in monitoring
      disease progression of FECD. Further studies are needed to consolidate the
      findings.

PMID- 28751985
TI  - Public Awareness regarding Common Eye Diseases among Saudi Adults in Riyadh City:
      A Quantitative Study.
AB  - AIM: The current study aimed to evaluate the knowledge of eye disease and
      awareness of eye care among the Saudi adults and to explore existing eye-related
      misconceptions in the community. METHODS: A cross-sectional study was conducted
      in Riyadh city during May and June 2016. A self-administered anonymous online
      questionnaire was used to explore the most common misconceptions related to eye
      diseases and eye care. RESULTS: Out of 1000 individuals, only 711 (71.1%)
      participant responses were received. The participants' acceptable knowledge
      (score >=50%) was high about the eye problem in diabetes (88.6%), ocular trauma
      (81.2%), and other general eye diseases (91.3%), whereas low about refractive
      errors (63%), pediatric eye problems (51.5%), and glaucoma (14.8%). The variation
      in knowledge about specific ocular morbidities was significant (p < 0.001). The
      majority of participants reported sources of information about the common eye
      diseases and eye care encountered from the community, internet-based resources,
      and social media. CONCLUSIONS: The majority of the participants had awareness
      about the common eye diseases, whereas low percentage of participant's awareness
      about specific condition of eye diseases. Public eye health awareness should be
      more focused on social media and the internet to be able to cover the younger
      individuals of the community.

PMID- 28751986
TI  - Evaluation of Bleb Morphology and Reduction in IOP and Glaucoma Medication
      following Implantation of a Novel Gel Stent.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the Xen Gel Stent and provide a
      macro- and microscopic analyses of bleb morphology. METHODS: A prospective 12
      month study on patients with primary open-angle glaucoma. Patients underwent
      implantation of the XEN Gel Stent (Allergan INC, Dublin, Ireland) either alone or
      combined with a cataract surgery. Biomicroscopy, in vivo confocal microscopy
      (IVCM), and anterior segment-optical coherence tomography (AS-OCT) were used to
      assess bleb morphology. Safety parameters were adverse events, best corrected
      visual acuity, visual field, and corneal endothelial cell loss. A postoperative
      IOP <= 18 mmHg without or on medications was respectively defined as complete and
      qualified success while an IOP >= 18 mmHg was defined as failure. RESULTS: Twelve
      eyes of 11 patients were evaluated. At one year, 5 out of 10 patients available
      achieved a complete success while five were qualified success. AS-OCT showed that
      bleb wall reflectivity was significantly higher in the failure group; IVCM
      revealed that stromal density was significantly lower in the success group. No
      safety issues were recorded. CONCLUSION: Implantation of the XEN Gel Stent
      appears to be a safe and effective procedure. AS-OCT and IVCM may be helpful in
      bleb assessment.

PMID- 28751987
TI  - Hypertension Management in Brazil: Usual Practice in Primary Care-A Meta
      Analysis.
AB  - Knowing the usual clinical practice is relevant for evaluations in health care
      and economic policies of management of hypertension. This study aimed to describe
      the usual management of hypertension in the Brazilian primary healthcare system
      through a systematic review and meta-analysis. The search of population-based
      studies conducted in Brazil was undertaken using PubMed, EMBASE, and Brazilian
      databases. Eligible studies were those conducted in adults with hypertension
      (blood pressure (BP) >= 140/90 mmHg or using BP lowering drugs). Three datasets'
      data were analyzed: SESI study (in Brazilian workers); HIPERDIA (Brazilian
      Registration and Monitoring of Hypertensive and Diabetic Patients Program); and a
      population-based study. Meta-analysis has been performed using the fixed and
      random effect models. A total of 11 studies or data sets were included in the
      systematic review. Hypertensive individuals had, on average, 2.6 medical visits
      annually and 18.2% were on diuretics (n = 811 hypertensive patients) and 16.2% on
      ACE inhibitors (n = 1768 hypertensive patients). BP control rate ranged from 43.7
      to 67.5%; 35.5% had measured total cholesterol and 36.5% determined fasting
      plasma glucose in the previous 12 months. Thiazide diuretics and ACE inhibitors
      were the most used BP lowering medications as single drugs, but the control rate
      of hypertension is insufficient.

PMID- 28751988
TI  - Hepatitis B Vaccination Status among Health Care Workers in a Tertiary Hospital
      in Ethiopia.
AB  - BACKGROUND: Even though health professionals (HPs) need special consideration for
      hepatitis B virus (HBV) vaccination, this is not widely implemented in low- and
      middle-income countries. The aim of this study was to determine the vaccination
      status of health professionals against hepatitis B virus infection, to identify
      barriers to vaccination and to identify factors associated with vaccination
      status. METHODS: This cross-sectional study was conducted from June 1 to 15,
      2016. Data was collected using self-administered questionnaire and analysed using
      SPSS version 21. A test of association was done using binary logistic regression
      and P value less than 0.05 was considered statistically significant. RESULTS: Out
      of 286 HPs included in the study 28.7% received full course vaccination against
      HBV. The most frequently mentioned reasons for not being vaccinated against HBV
      are unavailability of the vaccine (58.2%) and its cost (18.5%). Age, marital
      status, level of education, and type of profession have significant association
      with vaccination status. CONCLUSION: HBV coverage among HPs in Gondar University
      Hospital (GUH) is inadequate. This is mostly due to unavailability of the vaccine
      and its cost. Vaccination status significantly varies based on level of
      education, type of profession, age, and marital status. We recommend making
      vaccines available and accessible.

PMID- 28751989
TI  - En Bloc Pancreaticoduodenectomy for Locally Advanced Right Colon Cancers.
AB  - Locally advanced right colon cancer may invade adjacent tissue and organs. Direct
      invasion of the duodenum and pancreas necessitates an en bloc resection.
      Previously, this challenging procedure was associated with high morbidity and
      mortality; however, today, this procedure can be done more safely in experienced
      centers. The aim of this study is to report our experience on en bloc right
      colectomy with pancreaticoduodenectomy for locally advanced right colon cancers.
      Between 2000 and 2012, 5 patients underwent en bloc multivisceral resection. No
      major morbidities or perioperative mortalities were observed. Median disease-free
      survival time was 24.5 months and median overall survival time was 42.1 (range:
      4.5-70.4) months in our series. One patient lived 70 months after multivisceral
      resection and underwent cytoreductive surgery and total pelvic exenteration
      during the follow-up period. In locally advanced right colon tumors, all
      adhesions should be considered as malign invasion and separation should not be
      done. The reasonable option for this patient is to perform en bloc
      pancreaticoduodenectomy and right colectomy. This procedure may result in long
      term survival with acceptable morbidity and mortality rates. Multidisciplinary
      teamwork and multimodality treatment alternatives may improve the results.

PMID- 28751990
TI  - Dermal Substitutes Use in Reconstructive Surgery for Skin Tumors: A Single-Center
      Experience.
AB  - Reconstructive surgery following skin tumor resection can be challenging.
      Treatment options after removing the tumor are skin grafting, local pedicled and
      axial flaps, or microsurgery for complex and extensive wounds correction.
      Recently, the use of dermal substitutes has been extended to reconstructive
      surgery in cutaneous oncology. Objectives. To report both a single-center
      experience using dermal substitutes in reconstructive surgery for skin
      malignancies and reconstructive surgery's outcomes. Methods and Results. Among
      thirteen patients, seven (53.8%) were male with mean age of 62.6 years. Regarding
      diagnosis, there were five cases (38.5%) of basal cell carcinoma (BCC), two
      (15.4%) of melanoma in situ, two (15.4%) of dermatofibrosarcoma protuberans, one
      (7.7%) of squamous cell carcinoma (SCC), one (7.7%) of angiosarcoma, and one
      (7.7%) of eccrine carcinoma (EC). The most common site of injury was scalp
      (53.8%) and lower limbs (23.1%). Seven (53.8%) patients used NPWT and six (46.2%)
      patients underwent Brown's dressing. The most frequent complication of the first
      stage was wound contamination (38.5%). Average time to second-stage skin grafting
      was 43.9 days. Three (23%) patients developed tumor recurrence and one died.
      Conclusions. Use of dermal substitutes in oncology can be an option for
      reconstruction after extended resections, providing good aesthetical and
      functional results.

PMID- 28751991
TI  - Midwives' Role in Providing Nutrition Advice during Pregnancy: Meeting the
      Challenges? A Qualitative Study.
AB  - This study explored the Australian midwives' role in the provision of nutrition
      advice. Little is known about their perceptions of this role, the influence of
      the model of care, and the barriers and facilitators that may influence them
      providing quality nutrition advice to pregnant women. Semistructured telephone
      interviews were undertaken with a subsample (n = 16) of the members of the
      Australian College of Midwives who participated in an online survey about
      midwives' nutrition knowledge, attitudes, and their confidence in providing
      nutrition advice during pregnancy. Thematic descriptive analysis was used to
      analyse the data. Midwives believed they have a vital role in providing nutrition
      advice to pregnant women in the context of health promotion. However, this was
      not reflected in the advice many of them provided, which in many accounts was
      passive and medically directed. The extent and efficacy of their role appear to
      be challenged by many structural barriers. Midwives suggested facilitators that
      may assist in overcoming these challenges. Midwives need assistance, support, and
      guidance to provide holistic nutrition advice that assists women to achieve
      healthy pregnancies. A collaborative approach between midwifery bodies, nutrition
      and education experts, and maternity care services may provide an effective way
      forward.

PMID- 28751992
TI  - Prostatic-Like Syndrome in a Woman with Chronic Lymphocytic Leukemia: Sequential
      Kinase Inhibitor Therapy.
AB  - Chronic lymphocytic leukemia (CLL) is an incurable lymphoproliferative disorder
      with a heterogeneous genetic and clinical course. Two kinase inhibitors,
      ibrutinib and idelalisib, have demonstrated achievement of complete and durable
      remissions in relapse/refractory genetically unselected CLL patients. We present
      a case of relapsed CLL with extensive disease and hourglass deformity of urinary
      bladder as a result of the compression of two extraperitoneal paravesical soft
      tissue bulky masses, with excellent response to sequential kinase inhibitor
      therapy.

PMID- 28751993
TI  - Multiple Spontaneous Intracranial-Extracranial Arterial Dissections in a Patient
      with Osteogenesis Imperfecta.
AB  - A 40-year-old male with osteogenesis imperfecta (OI) was admitted to the hospital
      with an acute right monoparesis. Diffusion-weighted MRI showed infarction in the
      territory of the left anterior cerebral artery (ACA) and in the left posterior
      cerebral artery (PCA). In his vascular imaging, occlusion of the left vertebral
      artery (VA) starting from V2 segment was consistent with dissection and
      pseudoaneurysm in the right ACA. We presented this case because of the presence
      of spontaneous and simultaneous occurrence of both intracranial and extracranial
      arterial dissections in OI.

PMID- 28751994
TI  - Hypercalcemia in Lung Cancer due to Simultaneously Elevated PTHrP and Ectopic
      Calcitriol Production: First Case Report.
AB  - Calcitriol-mediated hypercalcemia has been reported in malignant lymphomas and
      granulomatous diseases but not in lung carcinoma. We describe a patient with
      squamous cell lung carcinoma with hypercalcemia and elevated calcitriol levels. A
      60-year-old Caucasian male patient with stage IIIB squamous cell lung cancer
      developed hypercalcemia at 14.8 mg/dL two years after receiving chemotherapy and
      radiotherapy where labs showed a serum intact PTH: 7 pg/mL, PTHrP: 30 pmol/L,
      1,25-hydroxyvitamin D (calcitriol): 76 pg/mL, and 25-hydroxyvitamin D levels: <4
      ng/mL. Calcitriol levels were elevated despite undetectable 25-hydroxyvitamin D
      levels. There are no reported lung cancer cases with elevated calcitriol as an
      etiology of hypercalcemia. We believe that the elevated calcitriol levels in this
      case were due to a PTHrP-independent mechanism, possibly from either ectopic
      production of calcitriol in tumor cells or from increased activity of 1-alpha
      hydroxylase in the same cells. The patient died before the effects of prednisone
      therapy could be assessed. Studies are needed to investigate the cellular source
      of calcitriol and its role in hypercalcemia in patients with lung cancer.

PMID- 28751995
TI  - "Monocept": A Brief Report of Congenital Absence of the Long Head of the Biceps
      Tendon and Literature Review.
AB  - The long head of the biceps tendon plays an important role in shoulder stability
      and its functional absence has been shown to contribute to glenohumeral
      instability. Congenital absence of the long head to the biceps tendon is rare,
      although described in the literature. We report the case of an 18-year-old
      recreational athlete with recurrent shoulder instability and congenital absence
      of the long head of the biceps tendon (which we term "monocept") and mild
      ipsilateral upper extremity hemimelia. The patient was treated surgically with
      posterior capsular shift with anterior Bankart repair without complication. At 16
      month follow-up the patient has returned to recreational activity and has had an
      11.37-point improvement in his DASH score. The authors suggest that patients with
      this uncommon anatomic anomaly and clinical shoulder instability are more likely
      to require surgical treatment.

PMID- 28751996
TI  - Leiomyosarcoma and Squamous Cell Carcinoma Arising in Mature Cystic Teratoma of
      the Ovary.
AB  - The occurrence of malignant transformation in mature cystic teratoma of the ovary
      is rare, with squamous cell carcinoma being the most common histologic type.
      Sarcomatous transformation has been rarely described in the literature. We
      present a case of leiomyosarcoma with a minor component of squamous cell
      carcinoma arising in mature cystic teratoma of ovary in a 65-year-old woman. The
      malignant tumor showed two distinct components of sarcomatous and invasive
      epithelial elements, which were confirmed by immunostaining. To our knowledge,
      only four cases of leiomyosarcoma in ovarian mature cystic teratoma have been
      reported and this is a unique case report of leiomyosarcoma and squamous cell
      carcinoma arising in a mature cystic teratoma of ovary.

PMID- 28751997
TI  - Corrigendum to "Management Challenges in a Child with Chronic Hyponatremia: Use
      of V2 Receptor Antagonist".
AB  - [This corrects the article DOI: 10.1155/2017/3757423.].

PMID- 28751998
TI  - Blood Transfusions Correct Anemia and Improve Tissue Oxygenation in Surgical and
      Critically ill Patients.

PMID- 28751999
TI  - The Yin and Yang of Blood Transfusion.

PMID- 28752000
TI  - Inadverdent Perioperative Hypothermia.

PMID- 28752001
TI  - Ultrasound a Game Changer.

PMID- 28752002
TI  - Changing Definitions of Sepsis.
AB  - Sepsis is one of the main causes of morbidity and mortality in critically ill
      patients despite the use of modern antibiotics and resuscitation therapies.
      Outcomes in sepsis have improved overall, probably because of an enhanced focus
      on early diagnosis and other improvements in supportive care, but mortality rates
      still remain unacceptably high. The diagnosis and definition of sepsis is a
      critical problem due to the heterogeneity of this disease process. Although it is
      apparent that much more needs to be done to advance our understanding, sepsis and
      related terms remain difficult to define. A 1991 consensus conference developed
      initial definitions that systemic inflammatory response syndrome (SIRS) to
      infection would be called sepsis. Definitions of sepsis and septic shock were
      revised in 2001 to incorporate the threshold values for organ damage. In early
      2016, the new definitions of sepsis and septic shock have changed dramatically.
      Sepsis is now defined as life-threatening organ dysfunction caused by a
      dysregulated host response to infection. The consensus document describes organ
      dysfunction as an acute increase in total Sequential Organ Failure Assessment
      (SOFA) score two points consequently to the infection. A significant change in
      the new definitions is the elimination of any mention of SIRS. The Sepsis-3 Task
      Force also introduced a new bedside index, called the qSOFA, to identify outside
      of critical care units patients with suspected infection who are likely to
      develop sepsis. Recently updated the consensus definitions improved specificity
      compared with the previous descriptions.

PMID- 28752003
TI  - Approach to Perioperative Hypothermia by Anaesthesiology and Reanimation
      Specialist in Turkey: A Survey Investigation.
AB  - OBJECTIVE: The aim is to investigate the attitudes of anaesthesiologists working
      in Turkey on perioperative temperature monitoring. METHODS: The questionnaire
      comprised 25 questions. Data were obtained through the completion of the
      questionnaire by hand or via the web. RESULTS: Two hundred and four
      questionnaires were evaluated. Most physicians were working in government
      hospitals. We determined that 26% of physicians often use temperature monitoring
      and that physicians who works in university hospitals are significantly more
      common monitor the body temperature. There are different approachs on core
      temperature. The skin/axilla was the most preferred monitoring site; forced-air
      warming devices were the most common preferred heating systems. New-borns were
      the most commonly monitored group, and the Turkish Anaesthesiology and
      Reanimation Society guideline was the most commonly used reference. Physicians
      working in university or private hospitals were significantly more able to adjust
      the operating room temperature on demand. CONCLUSION: There are different
      applications to prevent perioperative hypothermia. Although physicians are aware
      of the effects of anaesthesia on hypothermia and the contribution of hypothermia
      to complications, this awareness was not enough for them to make temperature
      monitoring a routine practice. To make temperature monitoring a standard
      practice, we believe that more studies should be conducted and that this issue
      needs to be more frequently addressed in congresses, anaesthesia conferences and
      particularly in residency training clinics.

PMID- 28752004
TI  - Survey of Knowledge and Attitudes about Obstructive Sleep Apnoea Among Italian
      Anaesthetists.
AB  - OBJECTIVE: As the care of Obstructive Sleep Apnoea (OSA) patients remains
      heterogeneous, we hypothesized that it may reflect insufficient OSA
      knowledge/awareness among clinicians. METHODS: OSA Knowledge/Attitude
      Questionnaire (OSAKA) was translated into Italian and distributed to
      anaesthetists attending SIAARTI National Congress and Airways courses and Hands
      on Workshops from October 2012 to June 2013. RESULTS: In total, 370 anaesthetists
      returned the questionnaires (response rate, 62%); the median (interquartile range
      [IQR]) knowledge score was 12 (10-14), and the range was 1-17 with no difference
      by gender, age, professional title or years of practice. The knowledge items
      achieved a mean rate of corrected response of 66%+/-0.14%. With regard to
      attitude items, median (IQR) score was 15 (13-17) and range was 0-20. Females and
      anaesthetists with >15 years of practice reached higher scores, while anaesthesia
      residents showed a lower attitude score. Gender and professional title were
      statistically associated with the attitude score (gender: F=14.6, p=0.0002;
      professional title: F=4.72, p=0.0099), whereas a weak association was observed
      within years in practice and attitude score (F=2.6, p=0.0519). Knowledge score
      correlated positively with attitude score (r=0.4, p<0.0001). For knowledge
      domains, there was a positive correlation between pathophysiology (mid-grade:
      r=0.3, p<0.0001), symptoms (low grade: r=0.2, p<0.0001), diagnosis (mid grade:
      r=0.3, p<0.0001) and the attitude score. Correlation close to zero was observed
      for epidemiology and treatment domains (r=0.09, p=0.06; r=-0.01, p=0.78,
      respectively). CONCLUSION: The results of our survey demonstrate lack of
      knowledge about OSA and its treatment, revealing the need to update the syllabus
      of teaching in medical practice and in national health care policies to improve
      perioperative care.

PMID- 28752005
TI  - Ultrasound-Guided Cannulation of the Brachiocephalic Vein in Infants and Children
      is Useful and Stable.
AB  - OBJECTIVE: Ultrasound-guided (USG) cannulation of the brachiocephalic vein (BCV)
      has been shown to be technically easy. We hypothesised that adoption of USG in
      plane cannulation of the BCV as the primary approach to central venous
      cannulation at our institution would lead to central venous cannulation for a
      greater variety of indications. METHODS: We performed retrospective, descriptive
      comparison of all central lines placed in patients aged <16 years who underwent
      any surgical operation during calendar years 2012-2014 at a small, free-standing
      children's hospital. The use and management of a central line was reviewed until
      the patient was discharged from the hospital. Analysis of the data was performed
      using simple comparative statistical methods. RESULTS: Forty-nine patients were
      identified, 20 who weighed <10 kg and 29 who weighed >10 kg. Cannulation was
      successful in all patients. No significant late complications occurred. Catheters
      were well tolerated post-operatively, with no accidental dislodgement and no
      removal because of discomfort. The average duration of insertion was 6.3 (3-20+/
      3.77) days. Nine catheters were placed for access during emergency surgery. 15
      were placed in patients with difficult peripheral intravenous (PIV) access. The
      central lines remained in place until discharge in 79.6% of patients. In 40% of
      patients, the PIV catheter was removed, and the central line was retained because
      of preference. Total parenteral nutrition (TPN) was administered in 11 (22.4%)
      patients. CONCLUSION: Cannulation of BCV was well tolerated by children, with an
      average insertion duration of 6.3 days, which often lasted beyond the
      removal/failure of the PIV cannula. Catheters were useful for primary venous
      access during hospitalisation and for short TPN courses.

PMID- 28752006
TI  - Short-Term and Long-Term Effects of Dexamethasone on Cognitive Dysfunction
      Induced by Sevoflurane in Adult Rats.
AB  - OBJECTIVE: Postoperative cognitive dysfunction (POCD) is common after anaesthesia
      in elderly patients. However, it may appear in patients of all ages. The main
      pathogenesis of cognitive dysfunction remains unclear, although there is some
      evidence that brain inflammation may alter cognitive abilities. In the present
      study, we aim to evaluate short-term and long-term effects of dexamethasone on
      cognitive dysfunction induced by sevoflurane anaesthesia in adult rats. METHODS:
      Seven-month-old 30 male Wistar albino rats were randomised into three groups:
      sevoflurane group (exposure to sevoflurane), sevoflurane + dexamethasone group
      (exposure to sevoflurane and dexamethasone injection), and control group
      (exposure to 100% oxygen). Spatial learning and short-term (7 days after
      exposure) and long-term (30 days after exposure) memory were evaluated using
      Morris water maze test. RESULTS: Sevoflurane induced significant deficit in
      spatial learning and short-term and long-term memory in adult rats. Dexamethasone
      treated animals exposed to sevoflurane had equivalent performance as control
      animals in training and probe trials. CONCLUSION: Sevoflurane may impair spatial
      learning and short-term and long-term memories in adult rats. The co
      administration of dexamethasone and sevoflurane may ameliorate short-term and
      long-term cognitive dysfunctions induced by sevoflurane in adult rats.

PMID- 28752007
TI  - Importance of the Upper Extremity Position for a Safe and Effective Axillary
      Block: a Comparative Study.
AB  - OBJECTIVE: Our aim was to determine the ideal position of upper extremities
      during ultrasonography guidance for axillary block. The position that provides
      the shortest distance between the median and musculocutaneous nerves was assumed
      to be the most appropriate position for axillary block. METHODS: In this cross
      sectional study, 120 (45 female and 75 male) patients were placed in a position
      with a shoulder at 90 degrees  / elbow 90 degrees  (position 1) and a shoulder 90
      degrees  / elbow 0 degrees  (position 2). The intersection point of the biceps
      brachii muscle with the lower border of the pectoralis major muscle is defined as
      the proximal level (P). Distal level (D) is reffered as 5 cm below the proximal
      level. In the positions described above, the distance between median and
      musculocutaneous nerves was measured proximal (positions 1P and 2P) and distal
      levels (positions 1D and 2D). It was investigated whether these measurements
      differed between the groups and whether the body mass index or the gender.
      RESULTS: The shortest mean distance (10.24+/-3.95 mm) between the two nerves was
      determined when the shoulder position 90 degrees /elbow position 0 degrees  at
      the distal level (1D) and the longest mean distance (13.41+/-4.26 mm) was
      determined when shoulder position 90 degrees /elbow position 90 degrees  at the
      proximal level (2P). In all four cases, there was no difference in the results
      between men and women. There was no relationship between the measurement results
      and the body mass indexes and age of the patients. CONCLUSION: Appropriate
      positioning of the upper extremities is important for achieving optimal position
      during axillary block. Thereby, the procedure can be safely and effectively
      performed with lesser amounts of local anaesthetic solution and a decreased
      number of manoeuvres with needle during infiltration.

PMID- 28752008
TI  - Importance of Sonography for Guiding Central Venous Cannulation in Patients with
      Neurofibromatosis.
AB  - A 15-year-old boy with neurofibromatosis type 1 (NF1) was referred to us for
      central venous catheter insertion, and on ultrasound of the neck, he was found to
      have extensive involvement of the brachial plexus due to the nerve sheath tumour.
      Multiple hypoechogenic lesions resembling the internal jugular vein and internal
      carotid artery were visualised and could be differentiated from the vessels by
      Doppler ultrasound. The importance of analyzing sonographic images of nerve
      sheath tumours, which can mimic blood vessels, and the importance of Doppler
      ultrasound for guiding central venous catheters in such patients to avoid nerve
      injury are discussed in this case report.

PMID- 28752009
TI  - Absent Lung Deflation Because of Blockade Using an Endobronchial Blocker.
AB  - One-lung ventilation is required for various thoracic procedures. In addition,
      various strategies such as the use of double-lumen tube, uninvent tubes, and
      endobronchial blocker have been used for performing one-lung ventilation. Each of
      these techniques has its advantages and limitations. Certain factors for failure
      of endobronchial blocker to provide lung deflation has been described in
      literature. We report a different aetiology of failure of lung deflation,
      although the endobronchial blocker was appropriately placed.

PMID- 28752010
TI  - Predictive Value of Brain Arrest Neurological Outcome Scale (BrANOS) on Mortality
      and Morbidity After Cardiac Arrest.

PMID- 28752011
TI  - Re: Predictive Value of Brain Arrest Neurological Outcome Scale (BrANOS) on
      Mortality and Morbidity After Cardiac Arrest.

PMID- 28752012
TI  - The FALLS-Protocol, Another Way to Assess Circulatory Status Using Lung
      Ultrasound.

PMID- 28752013
TI  - Determination of Absence of Right Internal Jugular Vein During Ultrasonographic
      Guided Central Venous Cannulation.

PMID- 28752014
TI  - Principles of Dataset Versioning: Exploring the Recreation/Storage Tradeoff.
AB  - The relative ease of collaborative data science and analysis has led to a
      proliferation of many thousands or millions of versions of the same datasets in
      many scientific and commercial domains, acquired or constructed at various stages
      of data analysis across many users, and often over long periods of time.
      Managing, storing, and recreating these dataset versions is a non-trivial task.
      The fundamental challenge here is the storage-recreation trade-off: the more
      storage we use, the faster it is to recreate or retrieve versions, while the less
      storage we use, the slower it is to recreate or retrieve versions. Despite the
      fundamental nature of this problem, there has been a surprisingly little amount
      of work on it. In this paper, we study this trade-off in a principled manner: we
      formulate six problems under various settings, trading off these quantities in
      various ways, demonstrate that most of the problems are intractable, and propose
      a suite of inexpensive heuristics drawing from techniques in delay-constrained
      scheduling, and spanning tree literature, to solve these problems. We have built
      a prototype version management system, that aims to serve as a foundation to our
      DataHub system for facilitating collaborative data science. We demonstrate, via
      extensive experiments, that our proposed heuristics provide efficient solutions
      in practical dataset versioning scenarios.

PMID- 28752015
TI  - Survey of Provider Preferences Regarding the Route of Misoprostol for Induction
      of Labor at Term.
AB  - Objective  To survey obstetrical provider preferences regarding use of
      misoprostol for induction of labor (IOL). Methods  An anonymous 25-question
      survey was distributed at an American College of Obstetricians and Gynecologists
      (ACOG) joint District V and VII Meeting in 2014 to obstetrics providers. The same
      survey was sent electronically to local providers. A separate survey was emailed
      to the labor and delivery nurses at two of the teaching hospitals in
      Indianapolis. The surveys queried provider demographics, dosing practice for
      misoprostol, opinions regarding different dosing strategies, and instructions on
      buccal administration. Results  A total of 113 (46.5%) providers responded. Of
      these, 92.9% used misoprostol for IOL, 73% preferred the vaginal route, 20%
      preferred buccal administration, and 7% oral administration. Only resident
      physician and midwife providers endorsed buccal route preference. Being a midwife
      independently predicted a preference for using buccal misoprostol (odds ratio
      [OR]: 125.8, 95% confidence interval [CI]: 7.9-1992.3). Additionally, 44 nurses
      completed the survey regarding administration techniques of buccal misoprostol.
      Also, 54.5% of nurses correctly instructed their patients on buccal
      administration techniques. Conclusion  Although not extensively studied, one
      fifth of providers, particularly nurse midwives, prefer buccal administration of
      misoprostol for IOL. The majority of nurses correctly administered buccal
      misoprostol. There may be a need for further study and education about buccal
      administration of misoprostol for IOL.

PMID- 28752016
TI  - Effect of Moderate to Vigorous Physical Activity Intervention on Improving
      Dementia Family Caregiver Physical Function: A Randomized Controlled Trial.
AB  - OBJECTIVE: Alzheimer's disease and related dementias (ADRD) affect more than five
      million Americans and their family caregivers. Caregiving creates challenges, may
      contribute to decreased caregiver health and is associated with $9.7 billion of
      caregiver health care costs. The purpose of this 12 month randomized clinical
      trial (RCT) was to examine if the Enhancing Physical Activity Intervention
      (EPAI), a moderate to vigorous physical activity (MVPA) treatment group, versus
      the Caregiver Skill Building Intervention (CSBI) control, would have greater: (1)
      MVPA adherence; and (2) physical function. METHODS: Caregivers were randomly
      assigned to EPAI or CSBI (N=211). MVPA was assessed using a self-report measure;
      and physical function was objectively assessed using two measures. Intention-to
      treat analyses used descriptive, categorical and generalized estimating equations
      (GEE), with an exchangeable working correlation matrix and a log link, to examine
      main effects and interactions in change of MVPA and physical function over time.
      RESULTS: At 12 months, EPAI significantly increased MVPA (p=<0.001) and number of
      steps (p=< .01); maintained stable caregiving hours and use of formal services;
      while CSBI increased hours of caregiving (p=<0.001) and used more formal services
      (p=<0.02). Qualitative physical function data indicated that approximately 50% of
      caregivers had difficulties completing physical function tests. CONCLUSION: The
      EPAI had a stronger 12 month effect on caregiver MVPA and physical function, as
      well as maintaining stability of caregiving hours and formal service use; while
      CSBI increased caregiving hours and use of formal services. A study limitation
      included greater EPAI versus CSBI attrition. Future directions are proposed for
      dementia family caregiver physical activity research.

PMID- 28752017
TI  - Attention Bias Modification (ABM): Review of Effects of Multisession ABM Training
      on Anxiety and Threat-Related Attention in High-Anxious Individuals.
AB  - Attention bias modification (ABM) aims to reduce anxiety by reducing attention
      bias (AB) to threat; however, effects on anxiety and AB are variable. This review
      examines 34 studies assessing effects of multisession-ABM on both anxiety and AB
      in high-anxious individuals. Methods include ABM-threat-avoidance (promoting
      attention-orienting away from threat), ABM-positive-search (promoting explicit,
      goal-directed attention-search for positive/nonthreat targets among
      negative/threat distractors), and comparison conditions (e.g., control-attention
      training combining threat-cue exposure and attention-task practice without AB
      modification). Findings indicate anxiety reduction often occurs during both ABM
      threat-avoidance and control-attention training; anxiety reduction is not
      consistently accompanied by AB reduction; anxious individuals often show no
      pretraining AB in orienting toward threat; and ABM-positive-search training
      appears promising in reducing anxiety. Methodological and theoretical issues are
      discussed concerning ABM paradigms, comparison conditions, and AB assessment. ABM
      methods combining explicit goal-directed attention-search for nonthreat/positive
      information and effortful threat-distractor inhibition (promoting top-down
      cognitive control during threat-cue exposure) warrant further evaluation.

PMID- 28752018
TI  - Project house water: a novel interdisciplinary framework to assess the
      environmental and socioeconomic consequences of flood-related impacts.
AB  - Protecting our water resources in terms of quality and quantity is considered one
      of the big challenges of the twenty-first century, which requires global and
      multidisciplinary solutions. A specific threat to water resources, in particular,
      is the increased occurrence and frequency of flood events due to climate change
      which has significant environmental and socioeconomic impacts. In addition to
      climate change, flooding (or subsequent erosion and run-off) may be exacerbated
      by, or result from, land use activities, obstruction of waterways, or
      urbanization of floodplains, as well as mining and other anthropogenic activities
      that alter natural flow regimes. Climate change and other anthropogenic induced
      flood events threaten the quantity of water as well as the quality of ecosystems
      and associated aquatic life. The quality of water can be significantly reduced
      through the unintentional distribution of pollutants, damage of infrastructure,
      and distribution of sediments and suspended materials during flood events. To
      understand and predict how flood events and associated distribution of pollutants
      may impact ecosystem and human health, as well as infrastructure, large-scale
      interdisciplinary collaborative efforts are required, which involve
      ecotoxicologists, hydrologists, chemists, geoscientists, water engineers, and
      socioeconomists. The research network "project house water" consists of a number
      of experts from a wide range of disciplines and was established to improve our
      current understanding of flood events and associated societal and environmental
      impacts. The concept of project house and similar seed fund and boost fund
      projects was established by the RWTH Aachen University within the framework of
      the German excellence initiative with support of the German research foundation
      (DFG) to promote and fund interdisciplinary research projects and provide a
      platform for scientists to collaborate on innovative, challenging research.
      Project house water consists of six proof-of-concept studies in very diverse and
      interdisciplinary areas of research (ecotoxicology, water, and chemical process
      engineering, geography, sociology, economy). The goal is to promote and foster
      high-quality research in the areas of water research and flood-risk assessments
      that combine and build off-laboratory experiments with modeling, monitoring, and
      surveys, as well as the use of applied methods and techniques across a variety of
      disciplines.

PMID- 28752019
TI  - Complex Frontal Pneumosinus Dilatans Associated with Meningioma: A Report of Two
      Cases and Associated Literature Review.
AB  - Introduction  Pneumosinus dilatans (PSD) is a rare phenomenon involving the
      expansion of the paranasal sinuses, without bony destruction or a mass.
      Previously documented cases have demonstrated simple expansion of a solitary air
      cell. We present two unique cases of PSD in the presence of meningioma, in which
      complex new cells developed within the frontal sinus. One of the two patients
      developed associated sinus disease. Case 1  A 28-year-old man presented with
      facial pain. A computed tomography scan showed an abnormally enlarged, septated
      right frontal sinus, not present on childhood scans. He underwent a modified
      endoscopic Lothrop approach to divide the septations, and his symptoms resolved.
      Case 2  A 72-year-old woman presented with a 3-month history of headaches. Scans
      revealed a left frontal meningioma and multiple enlarged, dilated left frontal
      air cells. She had no clinical sinusitis and therefore was managed
      conservatively. Conclusions  PSD has been widely documented in association with
      fibrous dysplasia and meningioma. The most prevalent theory of the mechanism of
      PSD is of obstruction of the sinus ostium causing sinus expansion through a "ball
      valve" effect. Our cases, which demonstrate septated PSD, suggest a more complex
      process involving local mediators and highlight the need to consider underlying
      meningioma in pneumosinus dilatans.

PMID- 28752020
TI  - Giant Epidermoid Cyst: A Rare Cause of Temporal Lobe Epilepsy.
AB  - Introduction  Epidermoid tumors represent approximately 0.3 to 1.8% of all
      intracranial brain tumors. Only 1.5% of all intracranial epidermoid cysts (ECs)
      invade the brain and secondary epilepsy is extremely rare. Since August 2014, a
      59-year-old male smoker had been presenting bad smell feelings, totaling four
      episodes with sudden onset and duration of 2 minutes. On September 2014, after a
      sense of smell episode, it evolved into loss of contact and automatic movements
      followed by generalized tonic-clonic movements. The brain magnetic resonance
      imaging revealed an extensive subtemporal lesion affecting anterior, middle, and
      posterior fossa with invasion of the choroidal fissure and projection to the
      temporal horn of the lateral ventricle. Pretemporal craniotomy with combined
      approaches, transsylvian and subtemporal, allowed for the excision of a white
      keratinized and softened lesion suggestive of EC. Discussion  The optimal
      surgical strategy in individuals with ECs and seizures is not established. The
      evaluation of the cause and risk-benefit must be held to choose the appropriate
      surgical strategy: lesionectomy, lobectomy, or amygdalohippocampectomy. In this
      case, a lesionectomy was performed due to an absence of evidence of involvement
      of hippocampus and amygdala. Conclusion  Epilepsy secondary to ECs is a rare
      association. Lesionectomy can be an option with good results without increasing
      the morbidity.

PMID- 28752021
TI  - Mycoremediation potential of Pleurotus species for heavy metals: a review.
AB  - Mycoremediation is one of the biotechniques that recruits fungi to remove toxic
      pollutants from environment in an efficient and economical manner. Mushrooms,
      macro-fungi, are among the nature's most important mycoremediators. Pleurotus
      species (also called oyster mushrooms) are considered to be the most popular and
      widely cultivated varieties worldwide and this might be attributed to their low
      production cost and higher yields. Apart from their nutritive and therapeutic
      properties, Pleurotus species have high biosorption potential due to their
      extensive biomass, i.e. mycelial production. The genus has been reported to
      accumulate high levels of heavy metals. The current state-of-the art review
      mainly summarises previous investigations carried out by researchers on different
      roles and mechanisms played by Pleurotus species on heavy metals mycoremediation.

PMID- 28752022
TI  - Ultrasound Imaging of Cystic Nephroma.
AB  - Cystic nephroma is a rare, benign multicystic lesion of the kidney. This tumor
      occurs both in children and in adults. In children, it is highly prevalent in
      males; in adults, it is more frequent in women. The term "cystic nephroma"
      represents two apparently different entities: pediatric cystic nephroma, a benign
      form thought to originate from metanephric tissue, and adult cystic nephroma,
      considered as a lesion of mixed epithelial stromal tumor. The clinical
      presentation may be a palpable mass or nonspecific symptoms such as abdominal
      pain, hematuria, and urinary tract infections. In this review, we summarize the
      ultrasound imaging features of cystic nephroma and describe the characteristics
      of the most common renal cystic lesions and the differential diagnosis of cystic
      nephroma with other renal cystic lesions.

PMID- 28752023
TI  - Trends in the Management of Small Renal Masses: A Survey of Members of the
      Endourological Society.
AB  - Treatment modalities for small renal masses (SRMs) include open or minimally
      invasive radical or partial nephrectomy, and laparoscopic or percutaneous
      ablations. Members of the Endourological Society were surveyed to evaluate how
      practitioner and clinical practice characteristics may be associated with the
      management of SRMs over time. The survey assessed characteristics of urologists
      (recency of residency and fellowship training, clinical practice type and
      location, and treatment modalities available) and their management of SRMs over
      the past year and over the course of the year 5 years prior. Of the 1495 surveys
      e-mailed, there were 129 respondents (8.6%). Comparing the past year to 5 years
      prior, there was increasing utilization of robotic partial nephrectomy (p <
      0.001) and robotic radial nephrectomy (p = 0.031). In contrast, there was
      decreasing utilization of open partial nephrectomy (p < 0.001), open radical
      nephrectomy (p = 0.039), laparoscopic partial nephrectomy (p = 0.002), and
      laparoscopic radical nephrectomy (p = 0.041). Employment of laparoscopic ablation
      decreased (p = 0.001), but that of percutaneous ablation did not change
      significantly. For masses treated with image-guided therapy, there was increasing
      utilization of microwave ablation (p = 0.008) and decreasing usage of
      radiofrequency ablation (p = 0.002). Future studies should focus on the most
      effective treatment modalities based on provider, patient, and tumor
      characteristics.

PMID- 28752024
TI  - Local environment and social factors in primary school children's afterschool
      commute in China.
AB  - The rapid decline in young children's active commutes to and from school has
      prompted investigations into ways to raise activity levels. The period after
      school is recognized as very important in the daily activity regime of primary
      school children. In this study, we examine the relative effects of local
      environmental factors and socio-economic status on children's after-school
      commute mode choice. Environmental factors are pedestrian priority streets,
      street intersection density, motorways, shops, and play spaces. Property values
      are used as a proxy for income. Twenty-four school districts are selected using
      intersection density and motorway length as criteria. All children's exit
      behaviors were film-recorded on October weekdays and extracted as four choices
      alone, in a group of children, on foot with a parent or guardian, on e-bike
      driven by an adult. A multinomial logistic regression reveals that gated
      communities, higher priced housing, motorways and bus stops are associated with
      children accompanied by adults. The presence of pedestrian streets is associated
      with children travelling alone and in groups. Greater travel distance is also
      associated with parents accompanying children on foot or on e-bike. The amount of
      play space is associated with children leaving school in groups. Overall, social
      and environmental factors are influential in the independent travel of primary
      school children after the school day ends in south China.

PMID- 28752025
TI  - Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone.
AB  - The natural compound thymoquinone, extracted from Nigella sativa (black cumin),
      is widely used in humans for its anti-oxidative properties. Thymoquinone is known
      for its acute endothelium-independent vasodilator effects in isolated rat aortae
      and pulmonary arteries, depending in part on activation of adenosine triphosphate
      sensitive potassium channels and inhibition of voltage-dependent calcium
      channels. The compound also improves endothelial dysfunction in mesenteric
      arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by
      inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment
      contractions in isolated arteries with endothelium of both rats and pigs. The
      endothelium-dependent augmentation it causes counterintuitively depends on biased
      activation of soluble guanylyl cyclase (sGC) producing inosine 3',5'-cyclic
      monophosphate (cyclic IMP) rather than guanosine 3',5'-cyclic monophosphate. This
      phenomenon shows a striking mechanistic similarity to the hypoxic augmentation
      previously observed in porcine coronary arteries. The cyclic IMP preferentially
      produced under thymoquinone exposure causes an increased contractility of
      arterial smooth muscle by interfering with calcium homeostasis. This brief review
      summarizes the vascular pharmacology of thymoquinone, focussing in particular on
      how the compound causes endothelium-dependent contractions by biasing the
      activity of sGC.

PMID- 28752026
TI  - Insects: an underrepresented resource for the discovery of biologically active
      natural products.
AB  - Nature has been the source of life-changing and -saving medications for
      centuries. Aspirin, penicillin and morphine are prime examples of Nature's gifts
      to medicine. These discoveries catalyzed the field of natural product drug
      discovery which has mostly focused on plants. However, insects have more than
      twice the number of species and entomotherapy has been in practice for as long as
      and often in conjunction with medicinal plants and is an important alternative to
      modern medicine in many parts of the world. Herein, an overview of current
      traditional medicinal applications of insects and characterization of isolated
      biologically active molecules starting from approximately 2010 is presented.
      Insect natural products reviewed were isolated from ants, bees, wasps, beetles,
      cockroaches, termites, flies, true bugs, moths and more. Biological activities of
      these natural products from insects include antimicrobial, antifungal, antiviral,
      anticancer, antioxidant, anti-inflammatory and immunomodulatory effects.

PMID- 28752027
TI  - The potential of natural products for targeting PPARalpha.
AB  - Peroxisome proliferator activated receptors (PPARs) alpha, -gamma and -beta/delta
      are ligand-activated transcription factors and members of the superfamily of
      nuclear hormone receptor. These receptors play key roles in maintaining glucose
      and lipid homeostasis by modulating gene expression. PPARs constitute a
      recognized druggable target and indeed several classes of drugs used in the
      treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g.
      fenofibrate and gemfibrozil) and diabetes (thiazolidinediones, e.g. rosiglitazone
      and pioglitazone) are ligands for the various PPAR isoforms. More precisely,
      antidiabetic thiazolidinediones act on PPARgamma, while PPARalpha is the main
      molecular target of antidyslipidemic fibrates. Over the past few years, our
      understanding of the mechanism underlying the PPAR modulation of gene expression
      has greatly increased. This review presents a survey on terrestrial and marine
      natural products modulating the PPARalpha system with the objective of
      highlighting how the incredible chemodiversity of natural products can provide
      innovative leads for this "hot" target.

PMID- 28752028
TI  - Approaches to establish Q-markers for the quality standards of traditional
      Chinese medicines.
AB  - Traditional Chinese medicine (TCM) has played a pivotal role in maintaining the
      health of Chinese people and is now gaining increasing acceptance around the
      global scope. However, TCM is confronting more and more concerns with respect to
      its quality. The intrinsic "multicomponent and multitarget" feature of TCM
      necessitates the establishment of a unique quality and bioactivity evaluation
      system, which is different from that of the Western medicine. However, TCM is
      investigated essentially as "herbal medicine" or "natural product", and the
      pharmacopoeia quality monographs are actually chemical-markers-based, which can
      ensure the consistency only in the assigned chemical markers, but, to some
      extent, have deviated from the basic TCM theory. A concept of "quality marker" (Q
      marker), following the "property-effect-component" theory, is proposed. The
      establishment of Q-marker integrates multidisciplinary technologies like natural
      products chemistry, analytical chemistry, bionics, chemometrics, pharmacology,
      systems biology, and pharmacodynamics, etc. Q-marker-based fingerprint and
      multicomponent determination conduce to the construction of more scientific
      quality control system of TCM. This review delineates the background, definition,
      and properties of Q-marker, and the associated technologies applied for its
      establishment. Strategies and approaches for establishing Q-marker-based TCM
      quality control system are presented and highlighted with a few TCM examples.

PMID- 28752029
TI  - Advances in ultrasound-targeted microbubble-mediated gene therapy for liver
      fibrosis.
AB  - Hepatic fibrosis develops as a wound-healing scar in response to acute and
      chronic liver inflammation and can lead to cirrhosis in patients with chronic
      hepatitis B and C. The condition arises due to increased synthesis and reduced
      degradation of extracellular matrix (ECM) and is a common pathological sequela of
      chronic liver disease. Excessive deposition of ECM in the liver causes liver
      dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a
      series of complications. However, fibrosis can be reversed before developing into
      cirrhosis and has thus been the subject of extensive researches particularly at
      the gene level. Currently, therapeutic genes are imported into the damaged liver
      to delay or prevent the development of liver fibrosis by regulating the
      expression of exogenous genes. One technique of gene delivery uses ultrasound
      targeting of microbubbles combined with therapeutic genes where the time and
      intensity of the ultrasound can control the release process. Ultrasound
      irradiation of microbubbles in the vicinity of cells changes the permeability of
      the cell membrane by its cavitation effect and enhances gene transfection. In
      this paper, recent progress in the field is reviewed with emphasis on the
      following aspects: the types of ultrasound microbubbles, the construction of an
      ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble
      mediated gene transfer and the application of ultrasound microbubbles in the
      treatment of liver fibrosis.

PMID- 28752030
TI  - Syringaresinol-4-O-beta-d-glucoside alters lipid and glucose metabolism in HepG2
      cells and C2C12 myotubes.
AB  - Syringaresinol-4-O-beta-d-glucoside (SSG), a furofuran-type lignan, was found to
      modulate lipid and glucose metabolism through an activity screen of lipid
      accumulation and glucose consumption, and was therefore considered as a promising
      candidate for the prevention and treatment of metabolic disorder, especially in
      lipid and glucose metabolic homeostasis. In this study, the effects of SSG on
      lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were
      further investigated. Treatment with SSG significantly inhibited lipid
      accumulation by oil red O staining and reduced the intracellular contents of
      total lipid, cholesterol and triglyceride in HepG2 cells. No effect was observed
      on cell viability in the MTT assay at concentrations of 0.1-10 MUmol/L. SSG also
      increased glucose consumption by HepG2 cells and glucose uptake by C2C12
      myotubes. Furthermore, real-time quantitative PCR revealed that the beneficial
      effects were associated with the down-regulation of sterol regulatory element
      binding proteins-1c, -2 (SREBP-1c, -2), fatty acid synthase (FAS), acetyl CoA
      carboxylase (ACC) and hydroxyl methylglutaryl CoA reductase (HMGR), and up
      regulation of peroxisome proliferator-activated receptors alpha and gamma
      (PPARalpha and PPARgamma). SSG also significantly elevated transcription activity
      of PPARgamma tested by luciferase assay. These results suggest that SSG is an
      effective regulator of lipogenesis and glucose consumption and might be a
      candidate for further research in the prevention and treatment of lipid and
      glucose metabolic diseases.

PMID- 28752031
TI  - Anti-diabetic effects and mechanisms of action of a Chinese herbal medicine
      preparation JQ-R in vitro and in diabetic KKAy mice.
AB  - Refined-JQ (JQ-R) is a mixture of refined extracts from Coptis chinensis
      (Ranunculaceae), Astragalus membranaceus (Leguminosae) and Lonicera japonica
      (Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional
      Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose
      metabolism and improves insulin sensitivity were studied in type 2 diabetic KKAy
      mice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ
      R improves insulin sensitivity, a model of insulin-resistant cells induced with
      palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression
      of factors involved in insulin signaling, stress, and inflammatory pathways were
      detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis
      and insulin resistance in a euglycemic clamp experiment and decreased fasting
      insulin levels in diabetic KKAy mice. JQ-R also improved the plasma lipid
      profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and
      decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS)
      levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose
      uptake with upregulated phosphorylation of AKT. The phosphorylation levels of
      nuclear factor kappa B (NF-kappaB p65), inhibitor of NF-kappaB (IkappaB alpha), c
      Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases
      (ERK1/2) were also changed after JQ-R treatment compared with the control group.
      Together these findings suggest that JQ-R improved glucose and lipid metabolism
      in diabetic KKAy mice. JQ-R directly enhanced insulin-stimulated glucose uptake
      in insulin-resistant myotubes with improved insulin signalling and inflammatory
      response and oxidative stress. JQ-R could be a candidate to achieve improved
      glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.

PMID- 28752032
TI  - Potassium 2-(l-hydroxypentyl)-benzoate attenuates neuroinflammatory responses and
      upregulates heme oxygenase-1 in systemic lipopolysaccharide-induced inflammation
      in mice.
AB  - A neuroinflammatory response is commonly involved in the progression of many
      neurodegenerative diseases. Potassium 2-(1-hydroxypentyl)-benzoate (PHPB), a
      novel neuroprotective compound, has shown promising effects in the treatment of
      ischemic stroke and Alzheimer's disease (AD). In the present study, the anti
      inflammatory effects of PHPB were investigated in the plasma and brain of C57BL/6
      mice administered a single intraperitoneal (i.p.) injection of lipopolysaccharide
      (LPS). Levels of iNOS and the cytokines TNFalpha, IL-1beta and IL-10 were
      elevated in plasma, cerebral cortex and hippocampus after LPS injection and the
      number of microglia and astrocytes in cortex and hippocampus were increased. LPS
      also upregulated the expression of heme oxygenase-1 (HO-1) in the cortex and
      hippocampus. PHPB reduced the levels of iNOS and cytokines in the plasma and
      brain, decreased the number of microglia and astrocytes and further enhanced the
      upregulation of HO-1. In addition, PHPB inhibited the LPS-induced phosphorylation
      of ERK, P38 and JNK. These results suggest that PHPB is a potential candidate in
      the treatment of neurodegenerative diseases through inhibiting neuroinflammation.

PMID- 28752033
TI  - 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors.
AB  - Dengue is a severe mosquito-borne viral infection causing half a million deaths
      annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue
      drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones
      analogues 4a-4j were synthesized and screened in silico against DENV2 NS2B/NS3
      protease to elucidate their binding mechanism and orientation around the active
      sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay
      using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5
      bis(arylidene)-4-piperidones (4e and 4j) emerged as promising lead molecules for
      novel protease inhibitors with an IC50 of 15.22 and 16.23 umol/L, respectively,
      compared to the standard, panduratin A, having IC50 of 57.28 umol/L.

PMID- 28752034
TI  - Phytochemical study of Illicium angustisepalum and its biological activities.
AB  - Sixteen compounds, including two new natural products (1 and 2), were obtained
      from the twigs of Illicium angustisepalum. The structures were elucidated based
      on NMR, MS, IR data and optical rotation values. Compounds 4, 5, 6 and 8
      displayed moderate antibacterial activities against clinical isolates; compounds
      4, 5, 8, 9 and 15 protected neural cells against oxidative stress; and compounds
      10 and 14 exhibited anti-acetylcholinesterase activity.

PMID- 28752035
TI  - Nine compounds from the root bark of Lycium chinense and their anti-inflammatory
      activitieslammatory activitiesretain-->.
AB  - Two new compounds, named lyciumlignan D (1) and lyciumphenyl propanoid A (2),
      along with seven known compounds, were isolated from the root bark of Lycium
      chinense. Their structures were elucidated using spectroscopic data (UV, IR, HR
      ESI-MS, 1D and 2D NMR, CD), as well as by comparison with those of the
      literature. Compounds 3-9 were isolated from this genus for the first time. In
      the in vitro assay, compounds 3, 6, and 7 exhibited stronger anti-inflammatory
      effects than the positive control curcumin at a concentration of 10 MUmol/L.

PMID- 28752036
TI  - Crystal structures, absolute configurations and molecular docking studies of
      naftopidil enantiomers as alpha1D-adrenoceptor antagonists.
AB  - Chiral drug naftopidil (NAF), a specific alpha1D-adrenoceptor (AR) antagonist for
      the treatment of benign prostatic hyperplasia, was used in racemic form for
      several decades. Our recent work declared that NAF enantiomers showed the same
      antagonistic effects on the alpha1D-AR, but the binding mechanism of these two
      stereochemical NAF isomers to the alpha1D receptor remained unclear. Herein, we
      reported the crystallographic structures of optically pure NAF stereoisomers for
      the first time and unambiguously determined their absolute configurations. The
      crystal data of R and S enantiomers matched satisfactorily the pharmacophore
      model for alpha1D-selective antagonists. Based on the constructed alpha1D
      homology model, molecular docking studies shed light on the molecular mechanism
      of NAF enantiomers binding to alpha1D-AR. The results indicated that NAF
      enantiomers exhibited the very similar binding poses and occupied the same
      binding pocket.

PMID- 28752037
TI  - In vivo retention of poloxamer-based in situ hydrogels for vaginal application in
      mouse and rat models.
AB  - The purpose of this study is to evaluate the in vivo retention capabilities of
      poloxamer-based in situ hydrogels for vaginal application with nonoxinol-9 as the
      model drug. Two in situ hydrogel formulations, which contained 18% poloxamer 407
      plus 1% poloxamer 188 (GEL1, relative hydrophobic) or 6% poloxamer 188 (GEL2,
      relative hydrophilic), were compared with respect to the rheological properties,
      in vitro hydrogel erosion and drug release. The vaginal retention capabilities of
      these hydrogel formulations were further determined in two small animal models,
      including drug quantitation of vaginal rinsing fluid in mice and isotope tracing
      with 99mTc in rats. The two formulations exhibited similar phase transition
      temperatures ranging from 27 to 32  degrees C. Increasing the content of
      poloxamer 188 resulted in higher rheological moduli under body temperature, but
      slightly accelerated hydrogel erosion and drug release. When compared in vivo,
      GEL1 was eliminated significantly slower in rat vagina than GEL2, while the
      vaginal retention of these two hydrogel formulations behaved similarly in mice.
      In conclusion, increases in the hydrophilic content of formulations led to faster
      hydrogel erosion, drug release and intravaginal elimination. Rats appear to be a
      better animal model than mice to evaluate the in situ hydrogel for vaginal
      application.

PMID- 28752038
TI  - Steroids hydroxylation catalyzed by the monooxygenase mutant 139-3 from Bacillus
      megaterium BM3.
AB  - The search of new substrates with pharmaceutical and industrial potential for
      biocatalysts including cytochrome P450 enzymes is always challenging. Cytochrome
      P450 BM3 mutant 139-3, a versatile biocatalyst, exhibited hydroxylation
      activities towards fatty acids and alkanes. However, there were limited reports
      about its hydroxylation activity towards steroids. Herein, an Escherichia coli
      based whole-cell extract containing the recombinant 139-3 protein was used as the
      biocatalyst to screen 13 steroids. Results revealed that 139-3 was able to
      specifically hydroxylate androstenedione (1) at 1alpha-position, generating a
      hydroxylated steroid 1alpha-OH-androstenedione (1a). To investigate whether C
      1alpha hydroxylation catalyzed by BM3 mutant 139-3 could be industrially used, an
      optimization of catalyzing conditions was performed. Accordingly, the BM3 mutant
      139-3 enzyme was observed to display maximum activity at 37  degrees C, under pH
      7.0 for 4 h, with 37% transformation rate. Moreover, four 139-3 variants were
      generated by random mutagenesis with the aim of improving its activity and
      expanding substrate scope. Surprisingly, these mutants, sharing a common mutated
      site R379S, lost their activities towards androstenedione (1). These data clearly
      indicated that arginine residue located at site 379 played key role in the
      hydroxylation activities of 139-3. Overall, these new findings broadened the
      substrate scope of 139-3 enzyme, thereby expanding its potential applications as
      a biocatalyst on steroids hydroxylation in pharmaceutical industry.

PMID- 28752039
TI  - Arylamine N-acetyltransferase 2 genotype-dependent N-acetylation of isoniazid in
      cryopreserved human hepatocytes.
AB  - Cryopreserved human hepatocytes were used to investigate the role of arylamine N
      acetyltransferase 2 (NAT2; EC 2.3.1.5) polymorphism on the N-acetylation of
      isoniazid (INH). NAT2 genotype was determined by Taqman allelic discrimination
      assay and INH N-acetylation was measured by high performance liquid
      chromatography. INH N-acetylation rates in vitro exhibited a robust and highly
      significant (P<0.005) NAT2 phenotype-dependent metabolism. N-acetylation rates in
      situ were INH concentration- and time-dependent. Following incubation for 24 h
      with 12.5 or 100 umol/L INH, acetyl-INH concentrations varied significantly (P =
      0.0023 and P = 0.0002) across cryopreserved human hepatocytes samples from rapid,
      intermediate, and slow acetylators, respectively. The clear association between
      NAT2 genotype and phenotype supports use of NAT2 genotype to guide INH dosing
      strategies in the treatment and prevention of tuberculosis.

PMID- 28752040
TI  - The reaction of cinnamaldehyde and cinnam(o)yl derivatives with thiols.
AB  - Spurred by the alleged relevance of the thia-Michael reaction in the bioactivity
      of various classes of cinnam(o)yl natural products and by the development of a
      quick NMR assay to study this reaction, we have carried out a systematic study of
      the "native" reactivity of these compounds with dodecanethiol and cysteamine as
      models, respectively, of simple thiols and reactive protein thiols that can
      benefit from iminium ion catalysis in Michael reactions. Cinnamoyl esters and
      amides, as well as cinnamyl ketones and oximes, did not show any reactivity with
      the two probe thiols, while cinnamaldehyde (1a) reacted with cysteamine to afford
      a mixture of a thiazoline derivative and compounds of multiple addition, and with
      aliphatic thiols to give a single bis-dithioacetal (6). Chalchones and their
      vinylogous C5-curcuminoid derivatives were the only cinnamoyl derivatives that
      gave a thia-Michael reaction. From a mechanistic standpoint, loss of conjugation
      in the adduct might underlie the lack of a native Michael reactivity. This
      property is restored by the presence of another conjugating group on the
      carbonyl, as in chalcones and C5-curcuminoids. A critical mechanistic revision of
      the chemical and biomedical literature on cinnamaldehyde and related compounds
      seems therefore required.

PMID- 28752041
TI  - Isocartormin, a novel quinochalcone C-glycoside from Carthamus tinctorius.
AB  - A new semi-quinonechalcone C-glycoside isocartormin along with cartormin and
      safflomin C were isolated from the water extract of Carthamus tinctorius L. The
      structure of isocartormin was determined by extensive analysis of HR-MS, 1D- and
      2D NMR data, and by comparison with those of cartormin reported previously by our
      group. Isocartormin was identified as a diastereoisomer of cartormin with a
      reverse configuration at C-18.

PMID- 28752042
TI  - Designing Cash Transfer Programs for an Older Population: The Mexican Case.
AB  - Aging populations and the prevalence of poverty in old age have led to the
      introduction of noncontributory pensions in many countries. We consider a number
      of alternative targeting approaches and simulate their effects in an empirical
      application in the State of Yucatan, Mexico. We compare the approaches with
      respect to leakage, under-coverage, and their effects on government budgets. We
      are also able to compare the simulated effects of one alternative with the
      observed effect of a recently introduced demogrant and find that the simulation
      is a close approximation of the empirical outcomes. We discuss issues of
      implementation and political feasibility.

PMID- 28752043
TI  - Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming.
AB  - BACKGROUND: The de novo biosynthesis of fatty acids (DNL) through fatty acid
      synthase (FASN) in adipocytes is exquisitely regulated by nutrients, hormones,
      fasting, and obesity in mice and humans. However, the functions of DNL in
      adipocyte biology and in the regulation of systemic glucose homeostasis are not
      fully understood. METHODS & RESULTS: Here we show adipocyte DNL controls
      crosstalk to localized sympathetic neurons that mediate expansion of beige/brite
      adipocytes within inguinal white adipose tissue (iWAT). Induced deletion of FASN
      in white and brown adipocytes of mature mice (iAdFASNKO mice) enhanced glucose
      tolerance, UCP1 expression, and cAMP signaling in iWAT. Consistent with induction
      of adipose sympathetic nerve activity, iAdFASNKO mice displayed markedly
      increased neuronal tyrosine hydroxylase (TH) and neuropeptide Y (NPY) content in
      iWAT. In contrast, brown adipose tissue (BAT) of iAdFASNKO mice showed no
      increase in TH or NPY, nor did FASN deletion selectively in brown adipocytes
      (UCP1-FASNKO mice) cause these effects in iWAT. CONCLUSIONS: These results
      demonstrate that downregulation of fatty acid synthesis via FASN depletion in
      white adipocytes of mature mice can stimulate neuronal signaling to control
      thermogenic programming in iWAT.

PMID- 28752044
TI  - Ca2+-associated triphasic pH changes in mitochondria during brown adipocyte
      activation.
AB  - OBJECTIVE: Brown adipocytes (BAs) are endowed with a high metabolic capacity for
      energy expenditure due to their high mitochondria content. While mitochondrial pH
      is dynamically regulated in response to stimulation and, in return, affects
      various metabolic processes, how mitochondrial pH is regulated during adrenergic
      stimulation-induced thermogenesis is unknown. We aimed to reveal the spatial and
      temporal dynamics of mitochondrial pH in stimulated BAs and the mechanisms behind
      the dynamic pH changes. METHODS: A mitochondrial targeted pH-sensitive protein,
      mito-pHluorin, was constructed and transfected to BAs. Transfected BAs were
      stimulated by an adrenergic agonist, isoproterenol. The pH changes in
      mitochondria were characterized by dual-color imaging with indicators that
      monitor mitochondrial membrane potential and heat production. The mechanisms of
      pH changes were studied by examining the involvement of electron transport chain
      (ETC) activity and Ca2+ profiles in mitochondria and the intracellular Ca2+
      store, the endoplasmic reticulum (ER). RESULTS: A triphasic mitochondrial pH
      change in BAs upon adrenergic stimulation was revealed. In comparison to a
      thermosensitive dye, we reveal that phases 1 and 2 of the pH increase precede
      thermogenesis, while phase 3, characterized by a pH decrease, occurs during
      thermogenesis. The mechanism of pH increase is partially related to ETC. In
      addition, the pH increase occurs concurrently with an increase in mitochondrial
      Ca2+. This Ca2+ increase is contributed to by an influx from the ER, and it is
      further involved in mitochondrial pH regulation. CONCLUSIONS: We demonstrate that
      an increase in mitochondrial pH is implicated as an early event in adrenergically
      stimulated BAs. We further suggest that this pH increase may play a role in the
      potentiation of thermogenesis.

PMID- 28752045
TI  - Angiopoietin-like 4 directs uptake of dietary fat away from adipose during
      fasting.
AB  - OBJECTIVE: Angiopoietin-like 4 (ANGPTL4) is a fasting-induced inhibitor of
      lipoprotein lipase (LPL) and a regulator of plasma triglyceride metabolism. Here,
      we examined the kinetics of Angptl4 induction and tested the hypothesis that
      ANGPTL4 functions physiologically to reduce triglyceride delivery to adipose
      tissue during nutrient deprivation. METHODS: Gene expression, LPL activity, and
      triglyceride uptake were examined in fasted and fed wild-type and Angptl4-/-
      mice. RESULTS: Angptl4 was strongly induced early in fasting, and this induction
      was suppressed in mice with access to food during the light cycle. Fasted Angptl4
      /- mice manifested increased LPL activity and triglyceride uptake in adipose
      tissue compared to wild-type mice. CONCLUSIONS: Angptl4 is induced early in
      fasting to divert uptake of fatty acids and triglycerides away from adipose
      tissues.

PMID- 28752046
TI  - Nicotinamide riboside kinases display redundancy in mediating nicotinamide
      mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells.
AB  - OBJECTIVE: Augmenting nicotinamide adenine dinucleotide (NAD+) availability may
      protect skeletal muscle from age-related metabolic decline. Dietary
      supplementation of NAD+ precursors nicotinamide mononucleotide (NMN) and
      nicotinamide riboside (NR) appear efficacious in elevating muscle NAD+. Here we
      sought to identify the pathways skeletal muscle cells utilize to synthesize NAD+
      from NMN and NR and provide insight into mechanisms of muscle metabolic
      homeostasis. METHODS: We exploited expression profiling of muscle NAD+
      biosynthetic pathways, single and double nicotinamide riboside kinase 1/2
      (NRK1/2) loss-of-function mice, and pharmacological inhibition of muscle NAD+
      recycling to evaluate NMN and NR utilization. RESULTS: Skeletal muscle cells
      primarily rely on nicotinamide phosphoribosyltransferase (NAMPT), NRK1, and NRK2
      for salvage biosynthesis of NAD+. NAMPT inhibition depletes muscle NAD+
      availability and can be rescued by NR and NMN as the preferred precursors for
      elevating muscle cell NAD+ in a pathway that depends on NRK1 and NRK2. Nrk2
      knockout mice develop normally and show subtle alterations to their NAD+
      metabolome and expression of related genes. NRK1, NRK2, and double KO myotubes
      revealed redundancy in the NRK dependent metabolism of NR to NAD+. Significantly,
      these models revealed that NMN supplementation is also dependent upon NRK
      activity to enhance NAD+ availability. CONCLUSIONS: These results identify
      skeletal muscle cells as requiring NAMPT to maintain NAD+ availability and reveal
      that NRK1 and 2 display overlapping function in salvage of exogenous NR and NMN
      to augment intracellular NAD+ availability.

PMID- 28752047
TI  - Amyloid formation disrupts the balance between interleukin-1beta and interleukin
      1 receptor antagonist in human islets.
AB  - OBJECTIVES: beta-cell dysfunction and apoptosis associated with islet
      inflammation play a key role in the pathogenesis of type 2 diabetes (T2D).
      Growing evidence suggests that islet amyloid, formed by aggregation of human
      islet amyloid polypeptide (hIAPP), contributes to islet inflammation and beta
      cell death in T2D. We recently showed the role of interleukin-1beta (IL
      1beta)/Fas/caspase-8 apoptotic pathway in amyloid-induced beta-cell death. In
      this study, we used human islets in culture as an ex vivo model of amyloid
      formation to: (1) investigate the effects of amyloid on islet levels of the
      natural IL-1 receptor antagonist (IL-1Ra); (2) examine if modulating the IL
      1beta/IL-1Ra balance can prevent amyloid-induced beta-cell Fas upregulation and
      apoptosis. METHODS: Isolated human islets (n = 10 donors) were cultured in
      elevated glucose (to form amyloid) with or without a neutralizing human IL-1beta
      antibody for up to 7 days. Parallel studies were performed with human islets in
      which amyloid formation was prevented by adeno-siRNA-mediated suppression of
      hIAPP expression (as control). beta-cell levels of IL-1Ra, Fas, apoptosis as well
      as islet function, insulin- and amyloid-positive areas, and IL-1Ra release were
      assessed. RESULTS: Progressive amyloid formation in human islets during culture
      was associated with alterations in IL-1Ra. Islet IL-1Ra levels were higher at
      early stages but were markedly reduced at later stages of amyloid formation.
      Furthermore, IL-1Ra release from human islets was reduced during 7-day culture in
      a time-dependent manner. These changes in IL-1Ra production and release from
      human islets during amyloid formation adversely correlated with islet IL-1beta
      levels, beta-cell Fas expression and apoptosis. Treatment with IL-1beta
      neutralizing antibody markedly reduced amyloid-induced beta-cell Fas expression
      and apoptosis, thereby improving islet beta-cell survival and function during
      culture. CONCLUSIONS: These data suggest that amyloid formation impairs the
      balance between IL-1beta and IL-1Ra in islets by increasing IL-1beta production
      and reducing IL-1Ra levels thereby promoting beta-cell dysfunction and death.
      Restoring the IL-1beta/IL-1Ra ratio may provide an effective strategy to protect
      islet beta-cells from amyloid toxicity in T2D.

PMID- 28752048
TI  - Myeloid protein tyrosine phosphatase 1B (PTP1B) deficiency protects against
      atherosclerotic plaque formation in the ApoE-/- mouse model of atherosclerosis
      with alterations in IL10/AMPKalpha pathway.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is the most prevalent cause of mortality
      among patients with Type 1 or Type 2 diabetes, due to accelerated
      atherosclerosis. Recent evidence suggests a strong link between atherosclerosis
      and insulin resistance due to impaired insulin receptor (IR) signaling. Moreover,
      inflammatory cells, in particular macrophages, play a key role in pathogenesis of
      atherosclerosis and insulin resistance in humans. We hypothesized that inhibiting
      the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative
      regulator of the IR, specifically in macrophages, would have beneficial anti
      inflammatory effects and lead to protection against atherosclerosis and CVD.
      METHODS: We generated novel macrophage-specific PTP1B knockout mice on
      atherogenic background (ApoE-/-/LysM-PTP1B). Mice were fed standard or pro
      atherogenic diet, and body weight, adiposity (echoMRI), glucose homeostasis,
      atherosclerotic plaque development, and molecular, biochemical and targeted
      lipidomic eicosanoid analyses were performed. RESULTS: Myeloid-PTP1B knockout
      mice on atherogenic background (ApoE-/-/LysM-PTP1B) exhibited a striking
      improvement in glucose homeostasis, decreased circulating lipids and decreased
      atherosclerotic plaque lesions, in the absence of body weight/adiposity
      differences. This was associated with enhanced phosphorylation of aortic Akt,
      AMPKalpha and increased secretion of circulating anti-inflammatory cytokine
      interleukin-10 (IL-10) and prostaglandin E2 (PGE2), without measurable
      alterations in IR phosphorylation, suggesting a direct beneficial effect of
      myeloid-PTP1B targeting. CONCLUSIONS: Here we demonstrate that inhibiting the
      activity of PTP1B specifically in myeloid lineage cells protects against
      atherosclerotic plaque formation, under atherogenic conditions, in an ApoE-/-
      mouse model of atherosclerosis. Our findings suggest for the first time that
      macrophage PTP1B targeting could be a therapeutic target for atherosclerosis
      treatment and reduction of CVD risk.

PMID- 28752049
TI  - Beta-adrenergic receptors are critical for weight loss but not for other
      metabolic adaptations to the consumption of a ketogenic diet in male mice.
AB  - OBJECTIVE: We have previously shown that the consumption of a low-carbohydrate
      ketogenic diet (KD) by mice leads to a distinct physiologic state associated with
      weight loss, increased metabolic rate, and improved insulin sensitivity [1].
      Furthermore, we identified fibroblast growth factor 21 (FGF21) as a necessary
      mediator of the changes, as mice lacking FGF21 fed KD gain rather than lose
      weight [2]. FGF21 activates the sympathetic nervous system (SNS) [3], which is a
      key regulator of metabolic rate. Thus, we considered that the SNS may play a role
      in mediating the metabolic adaption to ketosis. METHODS: To test this hypothesis,
      we measured the response of mice lacking all three beta-adrenergic receptors
      (beta-less mice) to KD feeding. RESULTS: In contrast to wild-type (WT) controls,
      beta-less mice gained weight, increased adipose tissue depots mass, and did not
      increase energy expenditure when consuming KD. Remarkably, despite weight-gain,
      beta-less mice were insulin sensitive. KD-induced changes in hepatic gene
      expression of beta-less mice were similar to those seen in WT controls eating KD.
      Expression of FGF21 mRNA rose over 60-fold in both WT and beta-less mice fed KD,
      and corresponding circulating FGF21 levels were 12.5 ng/ml in KD-fed wild type
      controls and 35.5 ng/ml in KD-fed beta-less mice. CONCLUSIONS: The response of
      beta-less mice distinguishes at least two distinct categories of physiologic
      effects in mice consuming KD. In the liver, KD regulates peroxisome proliferator
      activated receptor alpha (PPARalpha)-dependent pathways through an action of
      FGF21 independent of the SNS and beta-adrenergic receptors. In sharp contrast,
      induction of interscapular brown adipose tissue (BAT) and increased energy
      expenditure absolutely require SNS signals involving action on one or more beta
      adrenergic receptors. In this way, the key metabolic actions of FGF21 in response
      to KD have diverse effector mechanisms.

PMID- 28752050
TI  - Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet
      induced metabolic disorders.
AB  - OBJECTIVE: Brown and white adipose tissue exerts pleiotropic effects on systemic
      energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was
      recently identified as a brown fat-enriched secreted factor that ameliorates diet
      induced metabolic disorders, including insulin resistance and hepatic steatosis.
      However, the physiological mechanisms through which Nrg4 regulates energy balance
      and glucose and lipid metabolism remain incompletely understood. The aims of the
      current study were: i) to investigate the regulation of adipose Nrg4 expression
      during obesity and the physiological signals involved, ii) to elucidate the
      mechanisms underlying Nrg4 regulation of energy balance and glucose and lipid
      metabolism, and iii) to explore whether Nrg4 regulates adipose tissue secretome
      gene expression and adipokine secretion. METHODS: We examined the correlation of
      adipose Nrg4 expression with obesity in a cohort of diet-induced obese mice and
      investigated the upstream signals that regulate Nrg4 expression. We performed
      metabolic cage and hyperinsulinemic-euglycemic clamp studies in Nrg4 transgenic
      mice to dissect the metabolic pathways regulated by Nrg4. We investigated how
      Nrg4 regulates hepatic lipid metabolism in the fasting state and explored the
      effects of Nrg4 on adipose tissue gene expression, particularly those encoding
      secreted factors. RESULTS: Adipose Nrg4 expression is inversely correlated with
      adiposity and regulated by pro-inflammatory and anti-inflammatory signaling.
      Transgenic expression of Nrg4 increases energy expenditure and augments whole
      body glucose metabolism. Nrg4 protects mice from diet-induced hepatic steatosis
      in part through activation of hepatic fatty acid oxidation and ketogenesis.
      Finally, Nrg4 promotes a healthy adipokine profile during obesity. CONCLUSIONS:
      Nrg4 exerts pleiotropic beneficial effects on energy balance and glucose and
      lipid metabolism to ameliorate obesity-associated metabolic disorders. Biologic
      therapeutics based on Nrg4 may improve both type 2 diabetes and non-alcoholic
      fatty liver disease (NAFLD) in patients.

PMID- 28752051
TI  - Repletion of branched chain amino acids reverses mTORC1 signaling but not
      improved metabolism during dietary protein dilution.
AB  - OBJECTIVE: Dietary protein dilution (PD) has been associated with metabolic
      advantages such as improved glucose homeostasis and increased energy expenditure.
      This phenotype involves liver-induced release of FGF21 in response to amino acid
      insufficiency; however, it has remained unclear whether dietary dilution of
      specific amino acids (AAs) is also required. Circulating branched chain amino
      acids (BCAAs) are sensitive to protein intake, elevated in the serum of obese
      humans and mice and thought to promote insulin resistance. We tested whether
      replenishment of dietary BCAAs to an AA-diluted (AAD) diet is sufficient to
      reverse the glucoregulatory benefits of dietary PD. METHODS: We conducted AA
      profiling of serum from healthy humans and lean and high fat-fed or New Zealand
      obese (NZO) mice following dietary PD. We fed wildtype and NZO mice one of three
      amino acid defined diets: control, total AAD, or the same diet with complete
      levels of BCAAs (AAD + BCAA). We quantified serum AAs and characterized mice in
      terms of metabolic efficiency, body composition, glucose homeostasis, serum
      FGF21, and tissue markers of the integrated stress response (ISR) and mTORC1
      signaling. RESULTS: Serum BCAAs, while elevated in serum from hyperphagic NZO,
      were consistently reduced by dietary PD in humans and murine models. Repletion of
      dietary BCAAs modestly attenuated insulin sensitivity and metabolic efficiency in
      wildtype mice but did not restore hyperglycemia in NZO mice. While hepatic
      markers of the ISR such as P-eIF2alpha and FGF21 were unabated by dietary BCAA
      repletion, hepatic and peripheral mTORC1 signaling were fully or partially
      restored, independent of changes in circulating glucose or insulin. CONCLUSIONS:
      Repletion of BCAAs in dietary PD is sufficient to oppose changes in somatic
      mTORC1 signaling but does not reverse the hepatic ISR nor induce insulin
      resistance in type 2 diabetes during dietary PD.

PMID- 28752052
TI  - The role of ghrelin-responsive mediobasal hypothalamic neurons in mediating
      feeding responses to fasting.
AB  - OBJECTIVE: Ghrelin is a stomach-derived hormone that affects food intake and
      regulates blood glucose. The best-characterized actions of ghrelin are mediated
      by its binding to and activation of the growth hormone secretagogue receptor
      (GHSR; ghrelin receptor). Adequate examination of the identity, function, and
      relevance of specific subsets of GHSR-expressing neurons has been hampered by the
      absence of a suitable Cre recombinase (Cre)-expressing mouse line with which to
      manipulate gene expression in a targeted fashion within GHSR-expressing neurons.
      The present study aims to characterize the functional significance and
      neurocircuitry of GHSR-expressing neurons in the mediobasal hypothalamus (MBH),
      as they relate to ghrelin-induced food intake and fasting-associated rebound
      hyperphagia, using a novel mouse line in which Cre expression is controlled by
      the Ghsr promoter. METHODS: A Ghsr-IRES-Cre mouse line that expresses Cre
      directed by the Ghsr promoter was generated. The line was validated by comparing
      Cre activity in reporter mice to the known brain distribution pattern of GHSR.
      Next, the requirement of MBH GHSR-expressing neuronal activity in mediating food
      intake in response to administered ghrelin and in response to fasting was
      assessed after stereotaxic delivery of inhibitory designer receptor exclusively
      activated by designer drugs (DREADD) virus to the MBH. In a separate cohort of
      Ghsr-IRES-Cre mice, stereotaxic delivery of stimulatory DREADD virus to the MBH
      was performed to assess the sufficiency of MBH GHSR-expressing neuronal activity
      on food intake. Finally, the distribution of MBH GHSR-expressing neuronal axonal
      projections was assessed in the DREADD virus-injected animals. RESULTS: The
      pattern of Cre activity in the Ghsr-IRES-Cre mouse line mostly faithfully
      reproduced the known GHSR expression pattern. DREADD-assisted inhibition of MBH
      GHSR neuronal activity robustly suppressed the normal orexigenic response to
      ghrelin and fasting-associated rebound food intake. DREADD-assisted stimulation
      of MBH GHSR neuronal activity was sufficient to induce food intake. Axonal
      projections of GHSR-expressing MBH neurons were observed in a subset of
      hypothalamic and extra-hypothalamic regions. CONCLUSIONS: These results suggest
      that 1) activation of GHSR-expressing neurons in the MBH is required for the
      normal feeding responses following both peripheral administration of ghrelin and
      fasting, 2) activation of MBH GHSR-expressing neurons is sufficient to induce
      feeding, and 3) axonal projections to a subset of hypothalamic and/or extra
      hypothalamic regions likely mediate these responses. The Ghsr-IRES-Cre line
      should serve as a valuable tool to further our understanding of the functional
      significance of ghrelin-responsive/GHSR-expressing neurons and the neuronal
      circuitry within which they act.

PMID- 28752053
TI  - Dietary sugars, not lipids, drive hypothalamic inflammation.
AB  - OBJECTIVE: The hypothalamus of hypercaloric diet-induced obese animals is
      featured by a significant increase of microglial reactivity and its associated
      cytokine production. However, the role of dietary components, in particular fat
      and carbohydrate, with respect to the hypothalamic inflammatory response and the
      consequent impact on hypothalamic control of energy homeostasis is yet not clear.
      METHODS: We dissected the different effects of high-carbohydrate high-fat (HCHF)
      diets and low-carbohydrate high-fat (LCHF) diets on hypothalamic inflammatory
      responses in neurons and non-neuronal cells and tested the hypothesis that HCHF
      diets induce hypothalamic inflammation via advanced glycation end-products (AGEs)
      using mice lacking advanced glycation end-products (AGEs) receptor (RAGE) and/or
      the activated leukocyte cell-adhesion molecule (ALCAM). RESULTS: We found that
      consumption of HCHF diets, but not of LCHF diets, increases microgliosis as well
      as the presence of N(epsilon)-(Carboxymethyl)-Lysine (CML), a major AGE, in POMC
      and NPY neurons of the arcuate nucleus. Neuron-secreted CML binds to both RAGE
      and ALCAM, which are expressed on endothelial cells, microglia, and pericytes. On
      a HCHF diet, mice lacking the RAGE and ALCAM genes displayed less microglial
      reactivity and less neovasculature formation in the hypothalamic ARC, and this
      was associated with significant improvements of metabolic disorders induced by
      the HCHF diet. CONCLUSIONS: Combined overconsumption of fat and sugar, but not
      the overconsumption of fat per se, leads to excessive CML production in
      hypothalamic neurons, which, in turn, stimulates hypothalamic inflammatory
      responses such as microgliosis and eventually leads to neuronal dysfunction in
      the control of energy metabolism.

PMID- 28752054
TI  - Serotonergic modulation of the activity of GLP-1 producing neurons in the nucleus
      of the solitary tract in mouse.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) and 5-HT are potent regulators of food
      intake within the brain. GLP-1 is expressed by preproglucagon (PPG) neurons in
      the nucleus tractus solitarius (NTS). We have previously shown that PPG neurons
      innervate 5-HT neurons in the ventral brainstem. Here, we investigate whether PPG
      neurons receive serotonergic input and respond to 5-HT. METHODS: We employed
      immunohistochemistry to reveal serotonergic innervation of PPG neurons. We
      investigated the responsiveness of PPG neurons to 5-HT using in vitro Ca2+
      imaging in brainstem slices from transgenic mice expressing the Ca2+ indicator,
      GCaMP3, in PPG neurons, and cell-attached patch-clamp recordings. RESULTS: Close
      appositions from 5-HT-immunoreactive axons occurred on many PPG neurons.
      Application of 20 MUM 5-HT produced robust Ca2+ responses in NTS PPG dendrites
      but little change in somata. Dendritic Ca2+ spikes were concentration-dependent
      (2, 20, and 200 MUM) and unaffected by blockade of glutamatergic transmission,
      suggesting 5-HT receptors on PPG neurons. Neither activation nor blockade of 5
      HT3 receptors affected [Ca2+]i. In contrast, inhibition of 5-HT2 receptors
      attenuated increases in intracellular Ca2+ and 5-HT2C receptor activation
      produced Ca2+ spikes. Patch-clamp recordings revealed that 44% of cells decreased
      their firing rate under 5-HT, an effect blocked by 5-HT1A receptor antagonism.
      CONCLUSIONS: PPG neurons respond directly to 5-HT with a 5-HT2C receptor
      dependent increase in dendritic [Ca2+]i. Electrical responses to 5-HT revealed
      additional inhibitory effects due to somatic 5-HT1A receptors. Reciprocal
      innervation between 5-HT and PPG neurons suggests that the coordinated activity
      of these brainstem neurons may play a role in the regulation of food intake.

PMID- 28752055
TI  - Maternal obesity programs increased leptin gene expression in rat male offspring
      via epigenetic modifications in a depot-specific manner.
AB  - OBJECTIVE: According to the Developmental Origin of Health and Disease (DOHaD)
      concept, maternal obesity and accelerated growth in neonates predispose offspring
      to white adipose tissue (WAT) accumulation. In rodents, adipogenesis mainly
      develops during lactation. The mechanisms underlying the phenomenon known as
      developmental programming remain elusive. We previously reported that adult rat
      offspring from high-fat diet-fed dams (called HF) exhibited hypertrophic
      adipocyte, hyperleptinemia and increased leptin mRNA levels in a depot-specific
      manner. We hypothesized that leptin upregulation occurs via epigenetic
      malprogramming, which takes place early during development of WAT. METHODS: As a
      first step, we identified in silico two potential enhancers located upstream and
      downstream of the leptin transcription start site that exhibit strong dynamic
      epigenomic remodeling during adipocyte differentiation. We then focused on
      epigenetic modifications (methylation, hydroxymethylation, and histone
      modifications) of the promoter and the two potential enhancers regulating leptin
      gene expression in perirenal (pWAT) and inguinal (iWAT) fat pads of HF offspring
      during lactation (postnatal days 12 (PND12) and 21 (PND21)) and in adulthood.
      RESULTS: PND12 is an active period for epigenomic remodeling in both deposits
      especially in the upstream enhancer, consistent with leptin gene induction during
      adipogenesis. Unlike iWAT, some of these epigenetic marks were still observable
      in pWAT of weaned HF offspring. Retained marks were only visible in pWAT of 9
      month-old HF rats that showed a persistent "expandable" phenotype. CONCLUSIONS:
      Consistent with the DOHaD hypothesis, persistent epigenetic remodeling occurs at
      regulatory regions especially within intergenic sequences, linked to higher
      leptin gene expression in adult HF offspring in a depot-specific manner.

PMID- 28752057
TI  - Possible adverse effects of immunotherapy in non-small cell lung cancer;
      treatment and follow-up of three cases.
AB  - In the past decade novel agents are on the market for non-small cell lung cancer
      adenocarcinoma based on pharmacogenomics. The epidermal growth factor receptor
      mutation, anaplastic lymphoma kinase and programmed death-ligand 1 investigation
      is necessary in the everyday clinical practice for the oncologic patient.
      Immunotherapy is nowadays the novel therapy for advanced stage non-small cell
      lung cancer with two agents nivolumab and pembrolizumab. In the current case
      series we will present adverse effects from our centers and comment on the
      treatment and follow-up of the patients.

PMID- 28752056
TI  - The Munich MIDY Pig Biobank - A unique resource for studying organ crosstalk in
      diabetes.
AB  - OBJECTIVE: The prevalence of diabetes mellitus and associated complications is
      steadily increasing. As a resource for studying systemic consequences of chronic
      insulin insufficiency and hyperglycemia, we established a comprehensive biobank
      of long-term diabetic INSC94Y transgenic pigs, a model of mutant INS gene-induced
      diabetes of youth (MIDY), and of wild-type (WT) littermates. METHODS: Female MIDY
      pigs (n = 4) were maintained with suboptimal insulin treatment for 2 years,
      together with female WT littermates (n = 5). Plasma insulin, C-peptide and
      glucagon levels were regularly determined using specific immunoassays. In
      addition, clinical chemical, targeted metabolomics, and lipidomics analyses were
      performed. At age 2 years, all pigs were euthanized, necropsied, and a broad
      spectrum of tissues was taken by systematic uniform random sampling procedures.
      Total beta cell volume was determined by stereological methods. A pilot proteome
      analysis of pancreas, liver, and kidney cortex was performed by label free
      proteomics. RESULTS: MIDY pigs had elevated fasting plasma glucose and
      fructosamine concentrations, C-peptide levels that decreased with age and were
      undetectable at 2 years, and an 82% reduced total beta cell volume compared to
      WT. Plasma glucagon and beta hydroxybutyrate levels of MIDY pigs were chronically
      elevated, reflecting hallmarks of poorly controlled diabetes in humans. In total,
      ~1900 samples of different body fluids (blood, serum, plasma, urine,
      cerebrospinal fluid, and synovial fluid) as well as ~17,000 samples from ~50
      different tissues and organs were preserved to facilitate a plethora of
      morphological and molecular analyses. Principal component analyses of plasma
      targeted metabolomics and lipidomics data and of proteome profiles from pancreas,
      liver, and kidney cortex clearly separated MIDY and WT samples. CONCLUSIONS: The
      broad spectrum of well-defined biosamples in the Munich MIDY Pig Biobank that
      will be available to the scientific community provides a unique resource for
      systematic studies of organ crosstalk in diabetes in a multi-organ, multi-omics
      dimension.

PMID- 28752058
TI  - An elderly patient and an adult patients with isolated unilateral pulmonary
      arterial hypoplasia: Two cases reports and literature review of the literature.
AB  - Unilateral hypoplasia of a pulmonary artery (UHPA) is a rare condition that is
      usually associated with cardiac anomalies in childhood. In the absence of cardiac
      anomalies, patients may not be diagnosed until respiratory symptoms develop. We
      present two patients who were diagnosed as having isolated unilateral right
      pulmonary artery hypoplasia, one a woman aged 80 years, the other, a man aged 55
      years. To our knowledge, woman is the oldest patient with UHPA in the English
      medical literature. Awareness of this condition may contribute to the early
      recognition of these cases and planning of appropriate treatment.

PMID- 28752059
TI  - Microstructural abnormalities in white and gray matter in obese adolescents with
      and without type 2 diabetes.
AB  - AIMS/HYPOTHESES: In adults, type 2 diabetes and obesity have been associated with
      structural brain changes, even in the absence of dementia. Some evidence
      suggested similar changes in adolescents with type 2 diabetes but comparisons
      with a non-obese control group have been lacking. The aim of the current study
      was to examine differences in microstructure of gray and white matter between
      adolescents with type 2 diabetes, obese adolescents and healthy weight
      adolescents. METHODS: Magnetic resonance imaging data were collected from 15
      adolescents with type 2 diabetes, 21 obese adolescents and 22 healthy weight
      controls. Volumetric differences in the gray matter between the three groups were
      examined using voxel based morphology, while tract based spatial statistics was
      used to examine differences in the microstructure of the white matter. RESULTS:
      Adolescents with type 2 diabetes and obese adolescents had reduced gray matter
      volume in the right hippocampus, left putamen and caudate, bilateral amygdala and
      left thalamus compared to healthy weight controls. Type 2 diabetes was also
      associated with significant regional changes in fractional anisotropy within the
      corpus callosum, fornix, left inferior fronto-occipital fasciculus, left
      uncinate, left internal and external capsule. Fractional anisotropy reductions
      within these tracts were explained by increased radial diffusivity, which may
      suggest demyelination of white matter tracts. Mean diffusivity and axial
      diffusivity did not differ between the groups. CONCLUSION/INTERPRETATION: Our
      data shows that adolescent obesity alone results in reduced gray matter volume
      and that adolescent type 2 diabetes is associated with both white and gray matter
      abnormalities.

PMID- 28752061
TI  - Lethal neonatal rigidity and multifocal seizure syndrome with a new mutation in
      BRAT1.
AB  - Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal (RMFSL) (OMIM# 614498)
      is a rare and recently characterized epileptic encephalopathy that is related to
      variants in the BRAT1 gene (Breast Cancer 1-associated ataxia telangiectasia
      mutated activation-1 protein). In this report, an RMFSL case, who died in the
      10th month of the life, with rigidity, drug-resistant myoclonic seizures in the
      face and extremities, with, significant motor delays is presented. The exon
      sequence was determined and a new homozygous variant (C.2230_2237dupAACATGC) was
      detected. This RMFSL case with a homozygous variant in the BRAT1 gene, is the
      fourth one in the literature and the first one being reported from a Turkish
      family.

PMID- 28752060
TI  - Sleep onset uncovers thalamic abnormalities in patients with idiopathic
      generalised epilepsy.
AB  - The thalamus is crucial for sleep regulation and the pathophysiology of
      idiopathic generalised epilepsy (IGE), and may serve as the underlying basis for
      the links between the two. We investigated this using EEG-fMRI and a specific
      emphasis on the role and functional connectivity (FC) of the thalamus. We defined
      three types of thalamic FC: thalamocortical, inter-hemispheric thalamic, and
      intra-hemispheric thalamic. Patients and controls differed in all three measures,
      and during wakefulness and sleep, indicating disorder-dependent and state
      dependent modification of thalamic FC. Inter-hemispheric thalamic FC differed
      between patients and controls in somatosensory regions during wakefulness, and
      occipital regions during sleep. Intra-hemispheric thalamic FC was significantly
      higher in patients than controls following sleep onset, and disorder-dependent
      alterations to FC were seen in several thalamic regions always involving
      somatomotor and occipital regions. As interactions between thalamic sub-regions
      are indirect and mediated by the inhibitory thalamic reticular nucleus (TRN), the
      results suggest abnormal TRN function in patients with IGE, with a regional
      distribution which could suggest a link with the thalamocortical networks
      involved in the generation of alpha rhythms. Intra-thalamic FC could be a more
      widely applicable marker beyond patients with IGE.

PMID- 28752062
TI  - Prototheca: A Danger Underwater.
AB  - Prototheca wickerhamii rarely causes systemic infection in humans but when it
      occurs, there are coexisting comorbidities. This case illustrated shows the
      manifestation of this opportunistic microorganism in an immunosuppressed patient.
      The patient was successfully treated with Liposomal amphotericin B with complete
      resolution of the lesions.

PMID- 28752063
TI  - Urinary tract infection with Pasteurella multocida in a patient with cat exposure
      and abnormal urinary tract physiology: Case report and literature review.
AB  - Pasteurella multocida is a gram-negative organism that commonly colonizes the
      mouth of cats and dogs, and is known to cause infection in humans associated with
      animal bites or scratches. Sites of infection other than skin and soft tissue are
      rare, but have been reported in patients with specific risk factors including
      anatomical abnormalities or immunosuppression. Herein, we report a case of a
      symptomatic urinary tract infection caused by P. multocida in a 59 year old
      female who presented to the hospital with complaints of systemic symptoms
      including malaise, rigors, and chills, as well as thick, malodorous urine. The
      patient self-catheterized multiple times daily due to urostomy with Kock pouch.
      Treatment with piperacillin/tazobactam followed by amoxicillin resulted in
      resolution of the infection.

PMID- 28752064
TI  - Comments on: Kocova M, Anastasovska V. Comments on 'Newborn screening in
      southeastern Europe' published in Molecular Genetics and Metabolism, 2014 Sept
      Oct;113(1-2):42-45 by U. Groselj, M. ZerjavTansek, A. Smon, N. Angelkova, D.
      Anton, I. Baric, M. Djordjevic, L. Grimci, M. Ivanova, A. Kadam, V. Mulliqi
      Kotori, H. Maksic, O. Marginean, O. Margineanu, O. Milijanovic, F. Moldovanu, M.
      Muresan, S. Murko, M. Nanu, B. Repic Lampert, M. Samardzic, V. Sarnavka, A.
      Savov, M. Stojiljkovic, B. Suzic, R. Tincheva, H. Tahirovic, A. Toromanovic, N.
      Usurela, T. Battelino. Mol Genet Metab Rep. 2015 Nov 12;5:110. doi:
      10.1016/j.ymgmr.2015.11.003. eCollection 2015 Dec. Journal: Molecular Genetics
      and Metabolism Reports.

PMID- 28752065
TI  - Serous Borderline Tumor of the Testis and Associated Magnetic Resonance Imaging
      Findings.
AB  - Serous borderline tumor (SBT) of the testis is a rare, ovarian epithelial-type
      tumor of the testis. We present a case of SBT after radical orchiectomy in a 59
      year-old man who had 3-month progressive enlargement of his right hemi-scrotum,
      negative testicular tumor markers and scrotal ultrasound equivocal for
      malignancy. Magnetic resonance imaging (MRI) of the pelvis was obtained to aid
      with evaluation and showed marked hyperintensity on T2-weighted images with frond
      like nodular peripheral enhancement within right testis mass. These distinct MRI
      findings can help clinicians differentiate SBT from other testis tumors. Relapse
      has not been observed in 8 years of follow-up.

PMID- 28752066
TI  - A Case of Idiopathic Spontaneous Intratesticular Hemorrhage.
AB  - A 21-year-old man presented with acute-onset left lower abdominal pain that had
      initially developed 8 hours earlier. He was not given any medication including
      anti-coagulants. He denied trauma. On palpation, the left testis was slightly
      swollen and showed tenderness. The suspected diagnosis was testicular torsion,
      and surgical exploration was indicated. On visual inspection, the whole testis
      was black. The spermatic cord was neither distorted nor black. Testicular torsion
      could not be completely ruled out; thus, left orchiectomy was performed.
      Histopathology revealed diffuse intratesticular hemorrhage without the necrosis
      of seminiferous tubular cells. We encountered a case of idiopathic spontaneous
      intratesticular hemorrhage.

PMID- 28752067
TI  - Two-Stage Urethroplasty with Buccal Mucosa for Penoscrotal Hypospadias
      Reconstruction in a Male with a 46,XX Karyotype.
AB  - We present a case regarding a 32-year old African male with penoscrotal
      hypospadias, left cryptorchidism and a left inguinal hernia. There were moderate
      masculinization characteristics. He underwent a Lichtenstein hernia repair with
      perioperative biopsies of the left inguinal testis and epididymis. Microscopic
      examination showed a Sertoli-only left testis with Leydig-cell hyperplasia and
      the left epididymis consisted of ovarian tissue with corpora albicantia and
      maturing follicles. Endocrinological evaluation showed a sex-determining region Y
      (SRY) negative 46,XX karyotype. We successfully performed a two-stage
      urethroplasty with buccal mucosa graft to reconstruct his penoscrotal
      hypospadias.

PMID- 28752068
TI  - Management in Neonatal Priapism: Case and Review.
AB  - Neonatal priapism is uncommon and its cause is usually unknown, but it can
      generate anxiety for the parents and the pediatric team. The treatment in most
      cases is conservative and no sequelae are described.

PMID- 28752069
TI  - Hemangioendothelioma of the Bladder: The Youngest Case Report in A Child.
AB  - Hemangioendothelioma is a vascular tumor that commonly found in soft tissue,
      lungs, heart, liver, and bones, but it is very rare in bladder. We report a case
      of pediatric hemangioendothelioma of the bladder in a 2 years 7 months-old boy
      that treated with total excision of the bladder and bilateral
      ureterocutaneoustomy. This case is the second case in pediatric patients, and the
      youngest case that reported in a child. Our patient is doing well post
      operatively. But unfortunately interferon a-2b is not available in our hospital.
      At 3 months follow up, there was progressive progression of the tumor. Recurrent
      Abdominal mass was confirmed by Abdominal CT-Scan. The patient was died one week
      later. Interferon a-2b is might be an effective regimen on this tumor but further
      study is needed to confirm this statement.

PMID- 28752070
TI  - Polymers in our daily life.
AB  - Polymers are widely used advanced materials, which are found almost in every
      material used in our daily life. To date, the importance of polymers has been
      much more highlighted because of their applications in different dominions of
      sciences, technologies and industry - from basic uses to biopolymers and
      therapeutic polymers. The main aim of this editorial is to accentuate the
      pragmatic impacts of polymers in human daily life.

PMID- 28752071
TI  - An in vitro ethnopharmacological study on Prangos ferulacea: a wound healing
      agent.
AB  - Introduction: Traditionally Prangos ferulacea root is being used as an effective
      wound healing agent especially for pus-filled wounds both in human and stocks in
      the western north of Iran. Regarding the subject we decided to study P. ferulacea
      roots essential oil (PFE) for its antimicrobial and wound healing activities.
      Methods: The in vitro wound healing activity of PFE was evaluated in the mouse
      fibroblast cell line L929 using MTT assay of cell viability and cytotoxicity
      indices. Scratch assay as an in vitro model of wound healing assay was also
      conducted in this study. Moreover, the type I collagen content was used as an
      indicator of progress in wound healing process using Sircol collagen assay.
      Besides, PFE was subjected to GC/MS to identify the chemical constituents, and
      antimicrobical property was also evaluated against S. aureus, S. epidermidis, E.
      coli, P. aeruginosa,S. paratyphi and C. albicans using agar dilution method.
      Results: GC/MS analysis showed that the monoterpene hydrocarbones dominated in
      PFE, amounting to a total percentage of 95.1% with the major constituents: beta
      Phellandrene (32.1%), m-Tolualdehyde (26.2%), and delta-3-carene (25.8%). PFE
      inhibited the growth of S. aureus and P. aeruginusa with the MIC value of 20
      ug/mL. In addition, at the second day of treatment, PFE at concentrations of 4
      and 16 ug/mL significantly (P<0.001) enhanced the migration rate of L929 cells by
      87.05+/-2.4 and 63.5+/-0.08 %, respectively. Moreover, the collagen production by
      L929 cells was increased greatly (P<0.001). Conclusion: It is proposed that the
      excellent antimicrobial activity along with the significant increase of migration
      rate and collagen production by fibroblast cells might be associated with the
      high content and synergistic effect of the monoterpens, corroborating the
      traditional usage of this plant as a wound healing agent.

PMID- 28752072
TI  - Early endocrine disruptors exposure acts on 3T3-L1 differentiation and endocrine
      activity.
AB  - Introduction: Data from last years suggested that early exposure to endocrine
      disruptors (EDs) can predispose newborns to endocrine dysfunction of adipocytes,
      obesity, and associated disorders. The implication of EDs at low doses on
      adipocyte development has been poorly investigated. For instance, vinclozolin (V)
      is a dicarboximide fungicide widely used in agriculture since the 90's, alone or
      in mixture with genistein (G), an isoflavonoid from Leguminosae. This study aims
      to identify the effect of vinclozolin alone or with genistein, on adipose tissue
      properties using cell culture. Methods: In steroid-free conditions, 3T3-L1 pre
      adipocytes were induced to differentiate in the presence of EDs, singularly or in
      mixtures, for 2 days. DNA and triglyceride (TG) levels were measured on days 0, 2
      and 8 of differentiation. Leptin secretion was measured only on the eighth day.
      Results: We show that low doses of G (25 uM) and V (0.1 uM) inhibit pre
      adipocytes differentiation. This inhibition has been represented by a decreasing
      in DNA content (ug/well) and decreasing in TG accumulation (mg/mL) in 3T3-L1
      cells. Nevertheless, V increased the anti-adipogenic properties of G. Conclusion:
      This study confirms that EDs singularly or in mixtures, introduced during early
      stages of life, could affect the differentiation and the endocrine activity of
      adipocytes, and can act as potential factors for obesity.

PMID- 28752073
TI  - Surface plasmon resonance and molecular docking studies of bovine serum albumin
      interaction with neomycin: kinetic and thermodynamic analysis.
AB  - Introduction: The interactions between biomacromolecules such as serum albumin
      (SA) and various drugs have attracted increasing research attention in recent
      years. However, the study of SA with those drugs that have relatively high
      hydrophilicity and a lower affinity for SA could be a challenging issue. At the
      present study, the interaction of bovine SA (BSA) with neomycin as a hydrophilic
      drug has been investigated using surface plasmon resonance (SPR) and molecular
      docking methods. Methods: BSA was immobilized on the carboxymethyl dextran
      hydrogel sensor chip after activation of carboxylic groups through NHS/EDC and,
      then, the neomycin interaction with BSA at different concentrations (1-128 uM)
      was investigated. Results: Dose-response sensorgrams of BSA upon increasing
      concentration of neomycin has been shown through SPR analysis. The small KD value
      (4.96 e-7 at 40 degrees C) demonstrated high affinity of neomycin to BSA.
      Thermodynamic parameters were calculated through van't Hoff equation at 4
      different temperatures. The results showed that neomycin interacts with BSA via
      Van der Waals interactions and hydrogen bonds and increase of KD with temperature
      rising indicated that the binding process was entropy driven. Molecular docking
      study confirmed that hydrogen bond was the major intermolecular force stabilizing
      neomycin-BSA complex. Conclusion: The attained results showed that neomycin
      molecules can efficiently distribute within the body after interaction with BSA
      in spite of having hydrophilic properties. Besides, SPR can be considered as a
      useful instrument for study of the interaction of hydrophilic drugs with SA.

PMID- 28752074
TI  - Co-liquefaction with acetone and GC analysis of volatile compounds in exhaled
      breath as lung cancer biomarkers.
AB  - Introduction: A simple, rapid and low cost method for enrichment of volatile
      organic compounds (VOCs) from exhaled breath (EB) is presented. Methods: A 1000
      mL home-made extraction device was filled with EB. The VOCs were extracted and
      condensed in 0.5 mL acetone. Recognition of volatiles in the real studied EB
      samples was performed by a GC-MS. Results: The method displays an extraction
      efficiency of >86% with the enrichment factor of 1929 for octanal. Limits of
      detection and quantification, and linear dynamic range were 0.008, 0.026 and
      0.026-400 ng/mL respectively. Analysis of real samples showed the existence of
      more than 100 compounds in EB of healthy volunteers and patients with lung cancer
      before and after treatment. Exhaled octanal concentration was significantly
      higher in lung cancer patient than in healthy volunteers and lung cancer patient
      after treatment. Conclusion: Having used the proposed approach, high extraction
      recovery (up to 86%) was attained for the lung cancer marker, octanal, as an
      important biomarker. Our findings on smaples of EB of healthy controls and
      patients with lung cancer before and after treatment provide complelling evidence
      upon the effectiveness of the developed method.

PMID- 28752075
TI  - miR-155 effectively induces apoptosis in K562 Philadelphia positive cell line
      through upregulation of p27kip1.
AB  - Introduction: Chronic myelogenous leukemia (CML) is a myeloproliferative disorder
      caused by the Philadelphia chromosome translocation, at (9; 22), which results in
      BCR-ABL fusion tyrosine kinase oncoprotein. This fusion induces down-regulation
      of miR-155. Upregulation of miR-155 can influence cell fate via the effect on
      p27kip1 and apoptosis. The aim of this study was to induce apoptosis in K562 CML
      cell line by overexpression of miR-155. Methods: The K562 cell line was
      transfected with pLenti-III-pre mir155-GFP constructs through electroporation.
      Then, overexpression of miR-155 as well as the expression level of p27kip1 and c
      Myc was analyzed by quantitative PCR (qPCR). The level of p27 (Kip1) protein
      expression was measured by Western blot and the Annexin V method was carried out
      to investigate apoptosis. Results: Flow cytometric analysis results of K562 cells
      transfected with pLenti-III-pre mir155-GFP construct showed a significant
      increase in cell apoptosis. Gene expression and protein level of p27kip1 were
      upregulated. However, there was no change in c-Myc expression profile.
      Conclusion: miR-155 could be a promising approach to aid in the treatment of CML.
      However, further studies are required in this respect.

PMID- 28752076
TI  - Molecular machineries of pH dysregulation in tumor microenvironment: potential
      targets for cancer therapy.
AB  - Introduction: Cancer is an intricate disorder/dysfunction of cells that can be
      defined as a genetic heterogeneity in human disease. Therefore, it is
      characterized by several adaptive complex hallmarks. Among them, the pH
      dysregulation appears as a symbol of aberrant functions within the tumor
      microenvironment (TME). In comparison with normal tissues, in the solid tumors,
      we face with an irregular acidification and alkalinization of the extracellular
      and intracellular fluids. Methods: In this study, we comprehensively discussed
      the most recent reports on the hallmarks of solid tumors to provide deep insights
      upon the molecular machineries involved in the pH dysregulation of solid tumors
      and their impacts on the initiation and progression of cancer. Results: The
      dysregulation of pH in solid tumors is fundamentally related to the Warburg
      effect and hypoxia, leading to expression of a number of molecular machineries,
      including: NHE1, H+ pump V-ATPase, CA-9, CA-12, MCT-1, GLUT-1. Activation of
      proton exchangers and transporters (PETs) gives rise to formation of TME. This
      condition favors the cancer cells to evade from the anoikis and apoptosis,
      granting them aggressive and metastasis phenotype, as well as resistance to
      chemotherapy and radiation therapy. This review aimed to discuss the key
      molecular changes of tumor cells in terms of bio-energetics and cancer metabolism
      in relation with pH dysregulation. During this phenomenon, the intra- and
      extracellular metabolites are altered and/or disrupted. Such molecular
      alterations provide molecular hallmarks for direct targeting of the PETs by
      potent relevant inhibitors in combination with conventional cancer therapies as
      ultimate therapy against solid tumors. Conclusion: Taken all, along with other
      treatment strategies, targeting the key molecular machineries related to intra-
      and extracellular metabolisms within the TME is proposed as a novel strategy to
      inhibit or block PETs that are involved in the pH dysregulation of solid tumors.

PMID- 28752077
TI  - Prototheca zopfii Induced Ultrastructural Features Associated with Apoptosis in
      Bovine Mammary Epithelial Cells.
AB  - Prototheca zopfii infections are becoming global concerns in humans and animals.
      Bovine protothecal mastitis is characterized by deteriorating milk quality and
      quantity, thus imparting huge economic losses to dairy industry. Previous
      published studies mostly focused on the prevalence and characterization of P.
      zopfii from mastitis. However, the ultrastructural pathomorphological changes
      associated with apoptosis in bovine mammary epithelial cells (bMECs) are not
      studied yet. Therefore, in this study we aimed to evaluate the in vitro
      comparative apoptotic potential of P. zopfii genotype-I and -II on bMECs using
      flow cytometry, scanning electron microscopy (SEM), and transmission electron
      microscopy (TEM). The results showed fast growth rate and higher adhesion
      capability of genotype-II in bMECs as compared with genotype-I. The viability of
      bMECs infected with P. zopfii genotype-II was significantly decreased after 12 h
      (p < 0.05) and 24 h (p < 0.01) in comparison with control cells. Contrary,
      genotype-I couldn't show any significant effects on cell viability. Moreover,
      after infection of bMECs with genotype-II, the apoptosis increased significantly
      at 12 h (p < 0.05) and 24 h (p < 0.01) as compared with control group. Genotype-I
      couldn't display any significant effects on cell apoptosis. The host specificity
      of P. zopfii was also tested in mouse osteoblast cells, and the results suggest
      that genotype-I and -II could not cause any significant apoptosis in these cell
      lines. SEM interpreted the pathomorphological alterations in bMECs after
      infection. Adhesion of P. zopfii with cells and further disruption of
      cytomembrane validated the apoptosis caused by genotype-II under SEM. While
      genotype-1 couldn't cause any significant apoptosis in bMECs. Furthermore,
      genotype-II induced apoptotic manifested specific ultrastructure features, like
      cytoplasmic cavitation, swollen mitochondria, pyknosis, cytomembrane disruption,
      and appearance of apoptotic bodies under TEM. The findings of the current study
      revealed that genotype-II has the capability to invade and survive within the
      bMECs, thus imparting significant damages to the mammary cells which result in
      apoptosis. This study represents the first insights into the pathomorphological
      and ultrastructure features of apoptosis in bMECs induced by P. zopfii genotype
      II.

PMID- 28752078
TI  - Transcriptional Profiling of C. albicans in a Two Species Biofilm with Rothia
      dentocariosa.
AB  - Biofilms on silicone rubber voice prostheses are the major cause for frequent
      failure and replacement of these devices. The presence of both bacterial and
      yeast strains has been suggested to be crucial for the development of voice
      prosthetic biofilms. Polymicrobial biofilms that include Candida albicans and
      Rothia dentocariosa are the leading cause of voice prosthesis failure. An in
      vitro biofilm comprising these two organisms was developed on silicone rubber, a
      material used for Groningen button voice prosthesis. We found that this biofilm
      environment was not conducive for C. albicans growth or differentiation. Global
      transcriptional analyses of C. albicans biofilm cells grown with R. dentocariosa
      revealed that genes with functions related to cell cycle progression and hyphal
      development were repressed >2-fold. The mixed species biofilms were more compact
      and less robust compared to C. albicans mono-species biofilms, even when
      developed under conditions of continuous nutrient flow. Under these conditions R.
      dentocariosa also significantly inhibited C. albicans biofilm dispersal.
      Preferential adherence of R. dentocariosa to candidal hyphae was mediated by the
      adhesin Als3.

PMID- 28752079
TI  - Unique Chemokine Profiles of Lung Tissues Distinguish Post-chemotherapeutic
      Persistent and Chronic Tuberculosis in a Mouse Model.
AB  - There is a substantial need for biomarkers to distinguish latent stage from
      active Mycobacterium tuberculosis infections, for predicting disease progression.
      To induce the reactivation of tuberculosis, we present a new experimental animal
      model modified based on the previous model established by our group. In the new
      model, the reactivation of tuberculosis is induced without administration of
      immunosuppressive agents, which might disturb immune responses. To identify the
      immunological status of the persistent and chronic stages, we analyzed
      immunological genes in lung tissues from mice infected with M. tuberculosis. Gene
      expression was screened using cDNA microarray analysis and confirmed by
      quantitative RT-PCR. Based on the cDNA microarray results, 11 candidate cytokines
      genes, which were obviously up-regulated during the chronic stage compared with
      those during the persistent stage, were selected and clustered into three groups:
      (1) chemokine genes, except those of monocyte chemoattractant proteins (MCPs;
      CXCL9, CXCL10, CXCL11, CCL5, CCL19); (2) MCP genes (CCL2, CCL7, CCL8, CCL12); and
      (3) TNF and IFN-gamma genes. Results from the cDNA microarray and quantitative RT
      PCR analyses revealed that the mRNA expression of the selected cytokine genes was
      significantly higher in lung tissues of the chronic stage than of the persistent
      stage. Three chemokines (CCL5, CCL19, and CXCL9) and three MCPs (CCL7, CCL2, and
      CCL12) were noticeably increased in the chronic stage compared with the
      persistent stage by cDNA microarray (p < 0.01, except CCL12) or RT-PCR (p <
      0.01). Therefore, these six significantly increased cytokines in lung tissue from
      the mouse tuberculosis model might be candidates for biomarkers to distinguish
      the two disease stages. This information can be combined with already reported
      potential biomarkers to construct a network of more efficient tuberculosis
      markers.

PMID- 28752081
TI  - Absence of Nucleotide-Oligomerization-Domain-2 Is Associated with Less Distinct
      Disease in Campylobacter jejuni Infected Secondary Abiotic IL-10 Deficient Mice.
AB  - Human Campylobacter jejuni-infections are progressively increasing worldwide.
      Despite their high prevalence and socioeconomic impact the underlying mechanisms
      of pathogen-host-interactions are only incompletely understood. Given that the
      innate immune receptor nucleotide-oligomerization-domain-2 (Nod2) is involved in
      clearance of enteropathogens, we here evaluated its role in murine
      campylobacteriosis. To address this, we applied Nod2-deficient IL-10-/- (Nod2-/-
      IL-10-/-) mice and IL-10-/- counterparts both with a depleted intestinal
      microbiota to warrant pathogen-induced enterocolitis. At day 7 following peroral
      C. jejuni strain 81-176 infection, Nod2 mRNA was down-regulated in the colon of
      secondary abiotic IL-10-/- and wildtype mice. Nod2-deficiency did neither affect
      gastrointestinal colonization nor extra-intestinal and systemic translocation
      properties of C. jejuni. Colonic mucin-2 mRNA was, however, down-regulated upon
      C. jejuni-infection of both Nod2-/- IL-10-/- and IL-10-/- mice, whereas
      expression levels were lower in infected, but also naive Nod2-/- IL-10-/- mice as
      compared to respective IL-10-/- controls. Remarkably, C. jejuni-infected Nod2-/-
      IL-10-/- mice were less compromised than IL-10-/- counterparts and displayed less
      distinct apoptotic, but higher regenerative cell responses in colonic epithelia.
      Conversely, innate as well as adaptive immune cells such as macrophages and
      monocytes as well as T lymphocytes and regulatory T-cells, respectively, were
      even more abundant in large intestines of Nod2-/- IL-10-/- as compared to IL-10-/
      mice at day 7 post-infection. Furthermore, IFN-gamma concentrations were higher
      in ex vivo biopsies derived from intestinal compartments including colon and
      mesenteric lymph nodes as well as in systemic tissue sites such as the spleen of
      C. jejuni infected Nod2-/- IL-10-/- as compared to IL10-/- counterparts. Whereas,
      at day 7 postinfection anti-inflammatory IL-22 mRNA levels were up-regulated, IL
      18 mRNA was down-regulated in large intestines of Nod2-/- IL-10-/- vs. IL-10-/-
      mice. In summary, C. jejuni-infection induced less clinical signs and apoptosis,
      but more distinct colonic pro- and (of note) anti-inflammatory immune as well as
      regenerative cell responses in Nod2 deficient IL-10-/- as compared to IL-10-/-
      control mice. We conclude that, even though colonic Nod2 mRNA was down-regulated
      upon pathogenic challenge, Nod2-signaling is essentially involved in the well
      balanced innate and adaptive immune responses upon C. jejuni-infection of
      secondary abiotic IL-10-/- mice, but does neither impact pathogenic colonization
      nor translocation.

PMID- 28752082
TI  - Corrigendum to "Evaluation and Management of Skeletal Health in Celiac Disease:
      Position Statement".
AB  - [This corrects the article on p. 819 in vol. 26.].

PMID- 28752080
TI  - To Eat and to Be Eaten: Mutual Metabolic Adaptations of Immune Cells and
      Intracellular Bacterial Pathogens upon Infection.
AB  - Intracellular bacterial pathogens (IBPs) invade and replicate in different cell
      types including immune cells, in particular of the innate immune system (IIS)
      during infection in the acute phase. However, immune cells primarily function as
      essential players in the highly effective and integrated host defense systems
      comprising the IIS and the adaptive immune system (AIS), which cooperatively
      protect the host against invading microbes including IBPs. As countermeasures,
      the bacterial pathogens (and in particular the IBPs) have developed strategies to
      evade or reprogram the IIS at various steps. The intracellular replication
      capacity and the anti-immune defense responses of the IBP's as well as the
      specific antimicrobial responses of the immune cells of the innate and the AIS
      depend on specific metabolic programs of the IBPs and their host cells. The
      metabolic programs of the immune cells supporting or counteracting replication of
      the IBPs appear to be mutually exclusive. Indeed, recent studies show that upon
      interaction of naive, metabolically quiescent immune cells with IBPs, different
      metabolic activation processes occur which may result in the provision of a
      survival and replication niche for the pathogen or its eradication. It is
      therefore likely that within a possible host cell population subsets exist that
      are metabolically programmed for pro- or anti-microbial conditions. These
      metabolic programs may be triggered by the interactions between different
      bacterial agonistic components and host cell receptors. In this review, we
      summarize the current status in the field and discuss metabolic adaptation
      processes within immune cells of the IIS and the IBPs that support or restrict
      the intracellular replication of the pathogens.

PMID- 28752083
TI  - Recognition of Lynch Syndrome Amongst Newly Diagnosed Colorectal Cancers at St.
      Paul's Hospital.
AB  - BACKGROUND: Lynch Syndrome (LS) is the most common cause of inherited colorectal
      cancer (CRC). In British Columbia, most centres still use clinical criteria
      (Amsterdam II, Revised Bethesda, or the BC Cancer Agency's criteria) to determine
      who should undergo further first-line testing in the form of microsatellite
      instability or immunohistochemistry staining. Given the limitations with this
      strategy, LS is thought to be underrecognized. OBJECTIVE: To investigate whether
      LS is truly underrecognized when compared to the reported prevalence. METHODS: A
      retrospective chart review of all CRC cases diagnosed at St. Paul's Hospital from
      2010 to 2013 was conducted. RESULTS: 246 patients met inclusion criteria. 76%
      (83/109) with a family history of malignancy were unable to recall the specific
      malignancy or age of diagnosis. 18% (43/235) were only asked about a history of
      gastrointestinal related malignancy and 26% (65/246) met at least one of the
      three criteria but only 21% (13/63) received further investigation. Only 1.6%
      (4/246) had LS compared to the reported prevalence of 2-5% of all CRC cases.
      CONCLUSION: This data supports our hypothesis that LS is underrecognized. Issues
      at the patient, physician, and systems level need to be evaluated to determine
      where the limitations preventing appropriate testing are occurring.

PMID- 28752084
TI  - The Long-term Effect of Superficial Bladder Neck Incision on Ejaculation and
      Incontinence in Boys with Primary and Secondary Bladder Neck Obstruction.
AB  - OBJECTIVE: Superficial bladder neck incision (SBNI) is controversial at young
      age, with retrograde ejaculation after puberty as main concern. The aim of the
      study is to investigate the long-term effect of SBNI on ejaculation and
      incontinence in boys with primary and secondary bladder neck obstruction (BNO).
      MATERIALS AND METHODS: In boys with infravesical obstruction, SBNI was performed
      in case of a persistent BNO after earlier desobstruction or in case of primary
      severely obstructive bladder neck. SBNI was performed with a diathermy hook,
      always superficially (2-3 mm) and unilaterally at 7 O'clock. Males that had SBNI
      during childhood after posterior urethral valve incision or relief of other
      obstruction between 1986 and 2003 were included. Evaluation was done by
      International Continence Society male sex questionnaire, International Prostate
      Symptom Score, developmental International Consultation Modular Questionnaire on
      Urinary Incontinence, frequency volume chart, and uroflowmetry. RESULTS: Of 79
      traceable patients, 40 (50.6%) participated. Of these, 37 (92.5%) completed all
      questionnaires and 28 (70%) performed uroflowmetry. Median age at SBNI was 4.7
      years [interquartile range (IQR) 0.6-8.5] and was 19.6 years (IQR 17.3-20.9) at
      follow-up. All men had antegrade ejaculation, 4/37 (10.8%) reported possibly
      reduced ejaculatory volume. Eight (22%) had moderate lower urinary tract symptoms
      and two (5.4%) had moderate incontinence. Median maximum flow rate was 30.1 mL/s
      (IQR 24.4-42.6). CONCLUSION: SBNI in boys with severe infravesical obstruction
      can be done safely with preservation of antegrade ejaculation and no additional
      lower urinary tract dysfunction.

PMID- 28752085
TI  - Review of Pediatric Pheochromocytoma and Paraganglioma.
AB  - Pheochromocytoma (PCC) and paraganglioma (PGL) are rare chromaffin cell tumors
      which secrete catecholamines and form part of the family of neuroendocrine
      tumors. Although a rare cause of secondary hypertension in pediatrics, the
      presentation of hypertension in these patients is characteristic, and treatment
      is definitive. The gold standard for diagnosis is via measurement of plasma free
      metanephrines, with imaging studies performed for localization, identification of
      metastatic lesions and for surgical resection. Preoperative therapy with alpha
      blocking agents, beta blockers, and potentially tyrosine hydroxylase inhibitors
      aid in a safe pre-, intra- and postoperative course. PCC and PGL are inherited in
      as much as 80% of pediatric cases, and all patients with mutations should be
      followed closely given the risk of recurrence and malignancy. While the
      presentation of chromaffin cell tumors has been well described with multiple
      endocrine neoplasia, NF1, and Von Hippel-Lindau syndromes, the identification of
      new gene mutations leading to chromaffin cell tumors at a young age is changing
      the landscape of how clinicians approach such cases. The paraganglioma
      pheochromocytoma syndromes (SDHx) comprise familial gene mutations, of which the
      SDHB gene mutation carries a high rate of malignancy. Since the inheritance rate
      of such tumors is higher than previously described, genetic screening is
      recommended in all patients, and lifelong follow-up for recurrent tumors is a
      must. A multidisciplinary team approach allows for optimal health-care delivery
      in such children. This review serves to provide an overview of pediatric PCC and
      PGL, including updates on the preferred methods of imaging, guidelines on gene
      testing as well as management of hypertension in such patients.

PMID- 28752086
TI  - Editorial: Biological Engagement Programs: Reducing Threats and Strengthening
      Global Health Security Through Scientific Collaboration.

PMID- 28752087
TI  - Number and Severity of Type 2 Diabetes among Family Members Are Associated with
      Nutrition and Physical Activity Behaviors.
AB  - AIM: A binary measurement of type 2 diabetes (T2D) has been found not to
      influence behaviors. We aimed to examine the influence of other measures of
      family history such as number of relatives, genetic closeness of relatives, and
      severity of T2D of family members on nutrition and physical activity behaviors
      among college students. METHODS: Students across four colleges in Texas were
      sampled. Multiple linear regression models, controlling for covariates, were used
      to model results. Cross-sectional data were used. RESULTS: More number of
      relatives with T2D was associated with vegetable consumption (beta = 0.131, p =
      0.007) and exercise (beta = 0.129, p = 0.037). Having relatives with severe T2D
      was associated with vegetable consumption (beta = 0.157, p = 0.002) and exercise
      (beta = 106, p = 0.027). Closer genetic relationship with someone with T2D was
      associated with increased vegetable consumption (beta = 0.107, p = 0.023) and
      exercise (beta = 0.096, p = 0.047). CONCLUSION: It is likely that the severe
      complications that may accompany the relatives T2D or having an immediate family
      member living with T2D may in fact motivate other family members without T2D to
      modify their attitudes, beliefs, and knowledge about T2D, thus encourage health
      protective behaviors.

PMID- 28752088
TI  - Electron Transfer between Electrically Conductive Minerals and Quinones.
AB  - Long-distance electron transfer in marine environments couples physically
      separated redox half-reactions, impacting biogeochemical cycles of iron, sulfur
      and carbon. Bacterial bio-electrochemical systems that facilitate electron
      transfer via conductive filaments or across man-made electrodes are well-known,
      but the impact of abiotic currents across naturally occurring conductive and
      semiconductive minerals is poorly understood. In this paper I use cyclic
      voltammetry to explore electron transfer between electrodes made of common iron
      minerals (magnetite, hematite, pyrite, pyrrhotite, mackinawite, and greigite),
      and hydroquinones-a class of organic molecules found in carbon-rich sediments. Of
      all tested minerals, only pyrite and magnetite showed an increase in electric
      current in the presence of organic molecules, with pyrite showing excellent
      electrocatalytic performance. Pyrite electrodes performed better than
      commercially available glassy carbon electrodes and showed higher peak currents,
      lower overpotential values and a smaller separation between oxidation and
      reduction peaks for each tested quinone. Hydroquinone oxidation on pyrite
      surfaces was reversible, diffusion controlled, and stable over a large number of
      potential cycles. Given the ubiquity of both pyrite and quinones, abiotic
      electron transfer between minerals and organic molecules is likely widespread in
      Nature and may contribute to several different phenomena, including anaerobic
      respiration of a wide variety of microorganisms in temporally anoxic zones or in
      the proximity of hydrothermal vent chimneys, as well as quinone cycling and the
      propagation of anoxic zones in organic rich waters. Finally, interactions between
      pyrite and quinones make use of electrochemical gradients that have been
      suggested as an important source of energy for the origins of life on Earth.
      Ubiquinones and iron sulfide clusters are common redox cofactors found in
      electron transport chains across all domains of life and interactions between
      quinones and pyrite might have been an early analog of these ubiquitous systems.

PMID- 28752089
TI  - The Use of Operational Excellence Principles in a University Hospital.
AB  - The introduction of Operational Excellence in the Maastricht University Medical
      Center (MUMC+) has been the first of its kind and scale for a university
      hospital. The policy makers of the MUMC+ have combined different elements from
      various other business, management, and healthcare philosophies and frameworks
      into a unique mix. This paper summarizes the journey of developing this system
      and its most important aspects. Special attention is paid to the role of the
      operating rooms and the improvements that have taken place there, because of
      their central role in the working of the hospital. The MUMC+ is the leading
      tertiary healthcare center for the South-East region of The Netherlands and
      beyond. Regional, national, and international developments encouraged the MUMC+
      to start significantly reorganizing its care processes from 2009 onward. First
      experiments with Lean Six Sigma and Business Modeling were combined with lessons
      learned from other centers around the world to form the MUMC+'s own type of
      Operational Excellence. At the time of writing, many improvement projects of
      different types have been successfully completed. Every single department in the
      hospital now uses Operational Excellence and design thinking in general as a
      method to develop new models of care. An evaluation in 2014 revealed several
      opportunities for improvement. A large number of projects were in progress, but
      75% of all projects had not been completed, despite the first projects being
      initiated back in 2012. This led to a number of policy changes, mainly focusing
      on more intensive monitoring of projects and trying to do more improvement
      projects directly under the responsibility of the line manager. Focusing on
      patient value, continuous improvement, and the reduction of waste have proven to
      be very fitting principles for healthcare in general and specifically for
      application in a university hospital. Approaching improvement at a systems level
      while directly involving the people on the work floor in observing opportunities
      for improvement and realizing these has shown itself to be essential.

PMID- 28752090
TI  - Dr. Buzby's ToeGrips(r) Application Results in Minimal Changes in Kinetic Gait
      Parameters in Normal Dogs.
AB  - Poor traction on slick surfaces is difficult for dogs with neurologic deficits,
      osteoarthritis, or recovering from injury or surgery. Many dogs respond
      inappropriately to slick surfaces by decreasing digital pad-floor contact and
      extending their toenails. A device marketed to increase paw-floor friction in
      dogs was evaluated. Fifteen normal dogs underwent kinetic gait analysis before
      and after application of Dr. Buzby's ToeGrips(r). Ground reaction forces,
      including vertical peak force (VPF) and impulse for each limb, were measured and
      compared between pre- and post-application values. Stance time was significantly
      increased in all limbs after toe grip application. Stride velocity was slower in
      all limbs but significantly slower only in the left forelimb. VPF was
      significantly deceased in both hindlimbs after toe grip application, but the
      decrease was within the group SDs. Vertical impulse was significantly increased
      in both forelimbs and in the right hindlimb. Dr. Buzby's ToeGrips(r) result in a
      slower gait, with slightly decreased VPF in the hindlimbs and increased effort
      for propulsion kinetic changes were of minor magnitude and unlikely to be
      clinically relevant.

PMID- 28752091
TI  - Corrigendum to "Rehabilitation Training and Resveratrol Improve the Recovery of
      Neurological and Motor Function in Rats after Cerebral Ischemic Injury through
      the Sirt1 Signaling Pathway".
AB  - [This corrects the article DOI: 10.1155/2016/1732163.].

PMID- 28752092
TI  - Automated Image Analysis of HER2 Fluorescence In Situ Hybridization to Refine
      Definitions of Genetic Heterogeneity in Breast Cancer Tissue.
AB  - Human epidermal growth factor receptor 2 gene- (HER2-) targeted therapy for
      breast cancer relies primarily on HER2 overexpression established by
      immunohistochemistry (IHC) with borderline cases being further tested for
      amplification by fluorescence in situ hybridization (FISH). Manual interpretation
      of HER2 FISH is based on a limited number of cells and rather complex definitions
      of equivocal, polysomic, and genetically heterogeneous (GH) cases. Image analysis
      (IA) can extract high-capacity data and potentially improve HER2 testing in
      borderline cases. We investigated statistically derived indicators of HER2
      heterogeneity in HER2 FISH data obtained by automated IA of 50 IHC borderline
      (2+) cases of invasive ductal breast carcinoma. Overall, IA significantly
      underestimated the conventional HER2, CEP17 counts, and HER2/CEP17 ratio;
      however, it collected more amplified cells in some cases below the lower limit of
      GH definition by manual procedure. Indicators for amplification, polysomy, and
      bimodality were extracted by factor analysis and allowed clustering of the tumors
      into amplified, nonamplified, and equivocal/polysomy categories. The bimodality
      indicator provided independent cell diversity characteristics for all clusters.
      Tumors classified as bimodal only partially coincided with the conventional GH
      heterogeneity category. We conclude that automated high-capacity nonselective
      tumor cell assay can generate evidence-based HER2 intratumor heterogeneity
      indicators to refine GH definitions.

PMID- 28752093
TI  - Insomnia and Its Temporal Association with Academic Performance among University
      Students: A Cross-Sectional Study.
AB  - INTRODUCTION: Studies show that 9.4% to 38.2% of university students are
      suffering from insomnia. However, research data in developing countries is
      limited. Thus, the aim of the study was to assess insomnia and its temporal
      association with academic performance. METHODS AND MATERIALS: Institution based
      cross-sectional study was conducted with 388 students at Debre Berhan University.
      Data were collected at the nine colleges. Logistic and linear regression analysis
      was performed for modeling insomnia and academic performance with a p value
      threshold of 0.05, respectively. Data were entered using EPI-data version 3.1 and
      analyzed using SPSS version 20. RESULTS: The prevalence of insomnia was 61.6%.
      Field of study (p value = 0.01), worshiping frequency (p value = 0.048), marital
      status (p value = 0.03), and common mental disorder (p value < 0.001) were
      identified associated factors of insomnia. There was no significant association
      between insomnia and academic performance (p value = 0.53, beta = -0.04).
      Insomnia explained 1.2% (r2 = 0.012) of the difference in academic performance
      between students. CONCLUSIONS: Nearly 3 out of 5 students had insomnia. We
      recommended that universities would endorse sleep quality and mental health
      illness screening programs for students.

PMID- 28752094
TI  - Cardiovascular Emergencies.

PMID- 28752095
TI  - A Deep Morphological Characterization and Comparison of Different Dental
      Restorative Materials.
AB  - Giomer is a relatively new class of restorative material with aesthetics,
      handling and physical properties of composite resins, and benefits of glass
      ionomers: high radiopacity, antiplaque effect, fluoride release, and recharge. To
      verify the superior properties of Giomers, in this study, a deep morphological
      characterization has been performed with an in vitro comparative study among a
      Giomer (Beautifil(r) II by Shofu Dental Corporation, Osaka, Japan), a Compomer
      (Dyract Extra by Dentsply, Caulk, Germany), glass ionomer cement (Ketac fil plus
      by 3M ESPE), and a composite resin (Tetric Evoceram by Ivoclar). In particular,
      mechanical and optical properties and ageing effects have been compared to
      investigate materials similarities and differences. Indentation tests, UV-Visible
      spectroscopy, Raman spectroscopy, and weight loss after storage in saliva or
      sugary drink have been carried out to analyze materials behavior in real
      conditions. The results confirm the high quality of Giomer material and indicate
      possible improvements in their usage.

PMID- 28752096
TI  - Breast Density and Breast Cancer Incidence in the Lebanese Population: Results
      from a Retrospective Multicenter Study.
AB  - PURPOSE: To study the distribution of breast mammogram density in Lebanese women
      and correlate it with breast cancer (BC) incidence. METHODS: Data from 1,049
      women who had screening or diagnostic mammography were retrospectively reviewed.
      Age, menopausal status, contraceptives or hormonal replacement therapy (HRT),
      parity, breastfeeding, history of BC, breast mammogram density, and final BI-RADS
      assessment were collected. Breast density was analyzed in each age category and
      compared according to factors that could influence breast density and BC
      incidence. RESULTS: 120 (11.4%) patients had BC personal history with radiation
      and/or chemotherapy; 66 patients were postmenopausal under HRT. Mean age was
      52.58 +/- 11.90 years. 76.4% of the patients (30-39 years) had dense breasts.
      Parity, age, and menopausal status were correlated to breast density whereas
      breastfeeding and personal/family history of BC and HRT were not. In multivariate
      analysis, it was shown that the risk of breast cancer significantly increases
      3.3% with age (P = 0.005), 2.5 times in case of menopause (P = 0.004), and 1.4
      times when breast density increases (P = 0.014). CONCLUSION: Breast density
      distribution in Lebanon is similar to the western society. Similarly to other
      studies, it was shown that high breast density was statistically related to
      breast cancer, especially in older and menopausal women.

PMID- 28752097
TI  - Efficacy of Platelet-Rich Plasma in Retarding Intervertebral Disc Degeneration: A
      Meta-Analysis of Animal Studies.
AB  - OBJECTIVES: Several animal studies have demonstrated the positive effects of
      platelet-rich plasma (PRP) on disc degeneration retardation. The present meta
      analysis was to verify the efficacy of PRP in retarding disc degeneration in
      animal. METHODS: Relevant studies were identified and evaluated according to our
      inclusion and exclusion criteria. The standardized mean difference (SMD) and
      related 95% confidence interval (95% CI) were estimated to assess PRP efficiency.
      RESULTS: In total, eleven studies were included in this meta-analysis.
      Significant differences were found in the PRP treatment group, which showed
      increased disc height (SMD = 2.66, 95% CI: 1.86, 3.47, p = 0.000), increased MRI
      T2 signal intensity (SMD = -3.29, 95% CI: -4.44, -2.13, p = 0.000), and decreased
      histological degeneration grade (SMD = -4.28, 95% CI: -5.26, -3.30, p = 0.000).
      However, no significant increase in collagen II expression was found (SMD =
      25389.74, 95% CI: -27585.72, 78365.21, p = 0.348). Apart from the subgroup
      analysis of the disc height based on animal species (pig) and disc degeneration
      model (chymopapain induction), other subgroup analysis based on animal species
      (rabbit and rat), study design, disc degeneration model, and follow-up period
      demonstrated that PRP treatment can significantly restore disc height and
      increase MRI T2 signal intensity. CONCLUSIONS: PRP treatment is potentially
      effective in restoring disc height of rodent rabbit and rat, reducing
      histological degeneration grade, and increasing MRI T2 image signal. PRP
      injection may be promising therapy for retarding disc degeneration.

PMID- 28752099
TI  - Expressions Profiles of the Proteins Associated with Carbohydrate Metabolism in
      Rat Liver Regeneration.
AB  - Liver has a very amazing ability to regenerate from the remnant liver after
      injury or partial hepatectomy (PH). Carbohydrate metabolism plays a critical role
      in regeneration. Many signaling pathways are involved in the metabolism process.
      We analyzed the changes of proteins at 0-36 h after PH in rats using isobaric
      tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS-based
      quantitative proteomics strategy. The results showed that 110 proteins and 5
      signaling pathways related to carbohydrate metabolism in rat LR changed
      significantly. Based on a motif discovery method performed by iRegulon, we
      identified for the first time that the transcription factor SPIB whose motif was
      enriched among the differentiated genes associated with carbohydrate metabolism
      may play an important role in liver regeneration for the first time. The findings
      of this research provide a molecular basis for further unrevealing the mechanism
      of regeneration at priming stage (0-6 h) and proliferation stage (6-36 h) of LR
      in rats. At the same time, our studies provide more novel evidence for the
      signaling pathways which regulate carbohydrate metabolism from proteomics level.
      This study can provide some new thinking of liver regeneration and treatment of
      diseases associated with glucose metabolism.

PMID- 28752098
TI  - Recombinant Immunotoxin Therapy of Glioblastoma: Smart Design, Key Findings, and
      Specific Challenges.
AB  - Recombinant immunotoxins (RITs) refer to a group of recombinant protein-based
      therapeutics, which consists of two components: an antibody variable fragment or
      a specific ligand that allows RITs to bind specifically to target cells and an
      engineered toxin fragment that kills the target cells upon internalization. To
      date, over 1,000 RITs have been generated and significant success has been
      achieved in the therapy of hematological malignancies. However, the
      immunogenicity and off-target toxicities of RITs remain as significant barriers
      for their application to solid tumor therapy. A group of RITs have also been
      generated for the treatment of glioblastoma multiforme, and some have
      demonstrated evidence of tumor response and an acceptable profile of toxicity and
      safety in early clinical trials. Different from other solid tumors, how to
      efficiently deliver the RITs to intracranial tumors is more critical and needs to
      be solved urgently. In this article, we first review the design and expression of
      RITs, then summarize the key findings in the preclinical and clinical development
      of RIT therapy of glioblastoma multiforme, and lastly discuss the specific issues
      that still remain to forward RIT therapy to clinical practice.

PMID- 28752100
TI  - Downregulation of miR-214-3p May Contribute to Pathogenesis of Ulcerative Colitis
      via Targeting STAT6.
AB  - MicroRNAs (miRs) are small noncoding RNA molecules and recently have demonstrated
      that altered expression and functions are their tight association with ulcerative
      colitis (UC). Previous microarray study reported that miR-214 was downregulated
      in the sigmoid colon of patients with active UC, but the roles of miR-214 in the
      pathogenesis of UC remain to be elucidated. In this study, significant lower
      level of miR-214-3p and higher level of STAT6 in the intestinal mucosa of active
      UC patients compared with the health controls were confirmed by quantitative real
      time PCR. Results of luciferase reporter assays and western blot demonstrated
      that miR-214-3p directly targets STAT6 and negatively regulates the expression of
      STAT6 at the posttranscriptional level. Furthermore, the expression of miR-214-3p
      was decreased in TNF-alpha treated HT29 cells and STAT6 protein level was
      increased in a time-dependent manner. Silenced STAT6 and upregulation of miR-214
      3p could decrease the level of INF-gamma in TNF-alpha treated HT29 cells.
      Additionally, the results of the present study indicate that miR-214-3p and STAT6
      axis may be a novel therapeutic target for intestinal inflammation of patients
      with active UC.

PMID- 28752101
TI  - Implementation of a Large System-Wide Hepatitis C Virus Screening and Linkage to
      Care Program for Baby Boomers.
AB  - BACKGROUND: We implemented and evaluated a large health system-wide hepatitis C
      virus (HCV) screening and linkage to care program for persons born between 1945
      and 1965 ("baby boomers"). METHODS: An electronic health record (EHR) clinical
      decision support (CDS) tool for HCV screening for baby boomers was introduced in
      August 2015 for patients seen in the outpatient University of California, Los
      Angeles healthcare system setting. An HCV care coordinator was introduced in
      January 2016 to facilitate linkage to HCV care. We compared HCV testing in the
      year prior (August 2014-July 2015) to the year after (August 2015-July 2016)
      implementation of the CDS tool. Among patients with reactive HCV antibody
      testing, we compared outcomes related to the care cascade including HCV
      ribonucleic acid (RNA) testing, HCV RNA positivity, and linkage to HCV specialty
      care. RESULTS: During the study period, 19606 participants were screened for HCV
      antibody. Hepatitis C virus antibody screening increased 145% (from 5676 patients
      tested to 13930 tested) after introduction of the CDS intervention. Screening
      increased across all demographic groups including age, sex, and race/ethnicity,
      with the greatest increases among those in the older age groups. The addition of
      an HCV care coordinator increased follow-up HCV RNA testing for HCV antibody
      positive patients from 83% to 95%. Ninety-four percent of HCV RNA positive
      patients were linked to care postimplementation. CONCLUSIONS: Introduction of an
      EHR CDS tool and care coordination markedly increased the number of baby boomers
      screened for HCV, rates of follow-up HCV RNA testing, and linkage to specialty
      HCV care for patients with chronic HCV infection.

PMID- 28752102
TI  - Acute Kidney Injury and Urinary Biomarkers in Human Immunodeficiency Virus
      Associated Cryptococcal Meningitis.
AB  - BACKGROUND: Cryptococcus is the most common etiology of adult meningitis in
      Africa. Amphotericin B deoxycholate remains paramount to treatment, despite
      toxicities, including acute kidney injury (AKI). We assessed the ability of the
      following urine markers to predict AKI in patients who received amphotericin B:
      urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC),
      tissue inhibitor of metalloproteinases-2 (TIMP-2), and protein. METHODS: One
      hundred and thirty human immunodeficiency virus (HIV)-infected participants with
      cryptococcal meningitis were enrolled and received amphotericin and fluconazole
      for 2 weeks. We defined AKI as glomerular filtration rate (GFR) < 60 mL/min/1.73
      m2; measured urine NGAL, CysC, TIMP-2, and protein; and explored AKI incidence,
      risk factors, and associations with mortality using Cox proportional hazards
      models. RESULTS: Participants were 48% female with a median age of 35 years, a
      median CD4 count of 21 cells/MUL, and 44% died within 12 months. Incident AKI
      occurred in 42% and was associated with mortality (adjusted hazard ratio [aHR] =
      2.8; P < .001). Development of AKI was associated with female sex (P = .04) and
      with higher CD4 count (49 vs 14 cells/MUL; P < .01). Urine protein level in the
      highest quartile independently predicted AKI and mortality (aHR = 1.64, P = .04;
      aHR = 2.13, P = .02, respectively). Urine NGAL levels in the highest quartile
      independently predicted AKI (aHR = 1.65; P = .04). CONCLUSIONS: Acute kidney
      injury occurred in 42% of patients, and AKI was associated with mortality. Urine
      biomarkers, specifically urine protein, may be useful for antecedent prediction
      of amphotericin-associated AKI but need further evaluation.

PMID- 28752103
TI  - Evaluation of Viral Surrogate Markers for Study of Pathogen Dissemination During
      Simulations of Patient Care.
AB  - During patient care simulations, cauliflower mosaic virus DNA and bacteriophage
      MS2 performed similarly as surrogate markers of pathogen dissemination. These
      markers disseminated to the environment in a manner similar to Clostridium
      difficile spores but were more frequently detected on skin and clothing of
      personnel after personal protective equipment removal.

PMID- 28752104
TI  - Metrics for Performance Evaluation of Patient Exercises during Physical Therapy.
AB  - OBJECTIVE: The article proposes a set of metrics for evaluation of patient
      performance in physical therapy exercises. METHODS: Taxonomy is employed that
      classifies the metrics into quantitative and qualitative categories, based on the
      level of abstraction of the captured motion sequences. Further, the quantitative
      metrics are classified into model-less and model-based metrics, in reference to
      whether the evaluation employs the raw measurements of patient performed motions,
      or whether the evaluation is based on a mathematical model of the motions. The
      reviewed metrics include root-mean square distance, Kullback Leibler divergence,
      log-likelihood, heuristic consistency, Fugl-Meyer Assessment, and similar.
      RESULTS: The metrics are evaluated for a set of five human motions captured with
      a Kinect sensor. CONCLUSION: The metrics can potentially be integrated into a
      system that employs machine learning for modelling and assessment of the
      consistency of patient performance in home-based therapy setting. Automated
      performance evaluation can overcome the inherent subjectivity in human performed
      therapy assessment, and it can increase the adherence to prescribed therapy
      plans, and reduce healthcare costs.

PMID- 28752105
TI  - An entry-competent intermediate state of the HIV-1 envelope glycoproteins.
AB  - The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env)
      mediate viral entry and are the sole target of neutralizing antibodies. Recent
      studies show that the metastable HIV-1 Env trimer can transit among three
      conformational states: State 1, State 3, and State 2, corresponding to the
      "closed", "open" and intermediate conformations, respectively. During virus
      entry, binding to the CD4 receptor drives Env from state 1 to state 3. In the
      unliganded Env, transitions from the closed (State 1) conformation are restrained
      by intramolecular interactions among different Env residues, which regulate HIV-1
      Env conformation. Releasing the specific restraints on State 1 Env leads to
      increased occupancy of State 2, which is a functional conformation on the entry
      pathway and an obligate intermediate between State 1 and State 3. Frequent
      sampling of intermediate State 2 allows HIV-1 to infect cells expressing low
      levels of CD4, and leads to resistance to several broadly neutralizing antibodies
      as well as small-molecule inhibitors. Recent findings provide new mechanistic
      insights into the function and inhibition of HIV-1 Env and will contribute to the
      development of new therapeutic and prophylactic interventions to combat HIV-1.

PMID- 28752106
TI  - In vivo Analysis of Neutrophil Infiltration during LPS-induced Peritonitis.
AB  - Bacterial lipopolysaccharide (LPS) is present in the outer membrane of Gram
      negative bacteria and functions as pathogen-associated molecular pattern (PAMP)
      (Whitfield and Trent, 2014). LPS therefore is a potent activator of inflammatory
      responses leading to cytokine release and neutrophils recruitment. The lipid A
      moiety of LPS activates the complex consisting of the LPS binding protein (LBP),
      CD14, MD-2 and Toll-like receptor 4 (TLR4) and the non-canonical inflammasome
      linked caspases-4, 5 and 11, which in turn activate the canonical NLRP3
      inflammasome (Shi et al., 2014; Hagar et al., 2013; Kayagaki et al., 2013;
      Hoshino et al., 1999; Poltorak, 1998; Nagai et al., 2002; Park et al., 2009;
      Ratsimandresy et al., 2013). In particular, the cytokine interleukin (IL)-1beta
      produced in response to inflammasome activation has a crucial role in neutrophil
      recruitment through promoting neutrophil adhesion and migration (McDonald et al.,
      2010).This protocol allows studying of inflammatory response induced by LPS that
      affect neutrophil infiltration by tracking myeloperoxidase (MPO) activity in vivo
      (de Almeida et al., 2015).

PMID- 28752107
TI  - Muscle Histology Characterization Using H&E Staining and Muscle Fiber Type
      Classification Using Immunofluorescence Staining.
AB  - Muscle function is determined by its structure and fiber type composition. Here
      we describe a protocol to examine muscle histology and myofiber types using
      hematoxylin and eosin (H&E) and immunofluorescence staining, respectively. H&E
      stain nucleus in blue and cytoplasm in red, therefore allowing for morphological
      analyses, such as myofiber diameter, the presence of degenerated and regenerated
      myofibers, and adipocytes and fibrotic cells. Muscle fibers in adult skeletal
      muscles of rodents are classified into 4 subtypes based on the expression of
      myosin heavy chain proteins: Myh7 (type I fiber), Myh2 (type IIA fiber), Myh1
      (type IIX fiber), Myh4 (type IIB fiber). A panel of monoclonal antibodies can be
      used to specifically label these muscle fiber subtypes. These protocols are
      commonly used in the study of muscle development, growth and regeneration (for
      example: Wang et al., 2015; Nie et al., 2016; Yue et al., 2016; Wang et al.,
      2017).

PMID- 28752108
TI  - Measuring Behavioral Individuality in the Acoustic Startle Behavior in Zebrafish.
AB  - The objective of this protocol is to provide a detailed description for the
      construction and use of a behavioral apparatus, the zBox, for high-throughput
      behavioral measurements in larval zebrafish (Danio rerio). The zBox is used to
      measure behavior in multiple individuals simultaneously. Individual fish are
      housed in wells of multi-well plates and receive acoustic/vibration stimuli with
      simultaneous recording of behavior. Automated analysis of behavioral movies is
      performed with MATLAB scripts. This protocol was adapted from two of our
      previously published papers (Levitz et al., 2013; Pantoja et al., 2016). The zBox
      provides an easy to setup flexible platform for behavioral experiments in
      zebrafish larvae.

PMID- 28752109
TI  - Conjugation Assay for Testing CRISPR-Cas Anti-plasmid Immunity in Staphylococci.
AB  - CRISPR-Cas is a prokaryotic adaptive immune system that prevents uptake of mobile
      genetic elements such as bacteriophages and plasmids. Plasmid transfer between
      bacteria is of particular clinical concern due to increasing amounts of
      antibiotic resistant pathogens found in humans as a result of transfer of
      resistance plasmids within and between species. Testing the ability of CRISPR-Cas
      systems to block plasmid transfer in various conditions or with CRISPR-Cas
      mutants provides key insights into the functionality and mechanisms of CRISPR-Cas
      as well as how antibiotic resistance spreads within bacterial communities. Here,
      we describe a method for quantifying the impact of CRISPR-Cas on the efficiency
      of plasmid transfer by conjugation. While this method is presented in
      Staphylococcus species, it could be more broadly used for any conjugative
      prokaryote.

PMID- 28752110
TI  - Escherichia coli Infection of Drosophila.
AB  - Following septic insults, healthy insects, just like vertebrates, mount a complex
      immune response to contain and destroy pathogens. The failure to efficiently
      clear bacterial infections in immuno-compromised fly mutants leads to higher
      mortality rates which provide a powerful indicator for genes with important roles
      in innate immunity. The following protocol is designed to reproducibly inject a
      known amount of non-pathogenic E. coli into otherwise sterile flies and to
      measure the survival of flies after infection. The protocol can be easily adapted
      to different types of bacteria.

PMID- 28752111
TI  - Olfactory Cued Learning Paradigm.
AB  - Sensory stimulation leads to structural changes within the CNS (Central Nervous
      System), thus providing the fundamental mechanism for learning and memory. The
      olfactory circuit offers a unique model for studying experience-dependent
      plasticity, partly due to a continuous supply of integrating adult born neurons.
      Our lab has recently implemented an olfactory cued learning paradigm in which
      specific odor pairs are coupled to either a reward or punishment to study
      downstream circuit changes. The following protocol outlines the basic set up for
      our learning paradigm. Here, we describe the equipment setup, programming of
      software, and method of behavioral training.

PMID- 28752112
TI  - Lacunar-canalicular network in femoral cortical bone is reduced in aged women and
      is predominantly due to a loss of canalicular porosity.
AB  - The lacunar-canalicular network (LCN) of bone contains osteocytes and their
      dendritic extensions, which allow for intercellular communication, and are
      believed to serve as the mechanosensors that coordinate the processes of bone
      modeling and remodeling. Imbalances in remodeling, for example, are linked to
      bone disease, including fragility associated with aging. We have reported that
      there is a reduction in scale for one component of the LCN, osteocyte lacunar
      volume, across the human lifespan in females. In the present study, we explore
      the hypothesis that canalicular porosity also declines with age. To visualize the
      LCN and to determine how its components are altered with aging, we examined
      samples from young (age: 20-23 y; n = 5) and aged (age: 70-86 y; n = 6) healthy
      women donors utilizing a fluorescent labelling technique in combination with
      confocal laser scanning microscopy. A large cross-sectional area of cortical bone
      spanning the endosteal to periosteal surfaces from the anterior proximal femoral
      shaft was examined in order to account for potential trans-cortical variation in
      the LCN. Overall, we found that LCN areal fraction was reduced by 40.6% in the
      samples from aged women. This reduction was due, in part, to a reduction in
      lacunar density (21.4% decline in lacunae number per given area of bone), but
      much more so due to a 44.6% decline in canalicular areal fraction. While the
      areal fraction of larger vascular canals was higher in endosteal vs. periosteal
      regions for both age groups, no regional differences were observed in the areal
      fractions of the LCN and its components for either age group. Our data indicate
      that the LCN is diminished in aged women, and is largely due to a decline in the
      canalicular areal fraction, and that, unlike vascular canal porosity, this
      diminished LCN is uniform across the cortex.

PMID- 28752113
TI  - 2017 AGA Council Section Research Mentor Awardees.

PMID- 28752114
TI  - Do Animal Models of Acute Pancreatitis Reproduce Human Disease?
AB  - Acute pancreatitis is currently the most common cause of hospital admission among
      all nonmalignant gastrointestinal diseases. To understand the pathophysiology of
      the disease and as a potential step toward developing targeted therapies,
      attempts to induce the disease experimentally began more than 100 years ago.
      Recent decades have seen progress in developing new experimental pancreatitis
      models as well as elucidating many underlying cell biological and
      pathophysiological disease mechanisms. Some models have been developed to reflect
      specific causes of acute pancreatitis in human beings. However, the paucity of
      data relating to the molecular mechanisms of human disease, the likelihood that
      multiple genetic and environmental factors affect the risk of disease development
      and its severity, and the limited information regarding the natural history of
      disease in human beings make it difficult to evaluate the value of disease
      models. Here, we provide an overview of key models and discuss our views on their
      strengths for characterizing cell biological disease mechanisms or for
      identifying potential therapeutic targets. We also acknowledge their limitations.

PMID- 28752116
TI  - Multiple drug sensitization syndrome: A distinct phenotype associated with
      unrecognized Mycoplasma pneumonia infection.

PMID- 28752115
TI  - Acinar-to-Ductal Metaplasia Induced by Transforming Growth Factor Beta
      Facilitates KRASG12D-driven Pancreatic Tumorigenesis.
AB  - BACKGROUND & AIMS: Transforming growth factor beta (TGFbeta) acts either as a
      tumor suppressor or as an oncogene, depending on the cellular context and time of
      activation. TGFbeta activates the canonical SMAD pathway through its interaction
      with the serine/threonine kinase type I and II heterotetrameric receptors.
      Previous studies investigating TGFbeta-mediated signaling in the pancreas relied
      either on loss-of-function approaches or on ligand overexpression, and its
      effects on acinar cells have so far remained elusive. METHODS: We developed a
      transgenic mouse model allowing tamoxifen-inducible and Cre-mediated conditional
      activation of a constitutively active type I TGFbeta receptor (TbetaRICA) in the
      pancreatic acinar compartment. RESULTS: We observed that TbetaRICA expression
      induced acinar-to-ductal metaplasia (ADM) reprogramming, eventually facilitating
      the onset of KRASG12D-induced pre-cancerous pancreatic intraepithelial neoplasia.
      This phenotype was characterized by the cellular activation of apoptosis and
      dedifferentiation, two hallmarks of ADM, whereas at the molecular level, we
      evidenced a modulation in the expression of transcription factors such as
      Hnf1beta, Sox9, and Hes1. CONCLUSIONS: We demonstrate that TGFbeta pathway
      activation plays a crucial role in pancreatic tumor initiation through its
      capacity to induce ADM, providing a favorable environment for KRASG12D-dependent
      carcinogenesis. Such findings are highly relevant for the development of early
      detection markers and of potentially novel treatments for pancreatic cancer
      patients.

PMID- 28752117
TI  - Koebnerization phenomenon after broadband light therapy in a patient with
      cutaneous sarcoidosis.

PMID- 28752118
TI  - Localized skin-limited blastic plasmacytoid dendritic cell neoplasm: A subset
      with possible durable remission without transplantation.

PMID- 28752119
TI  - Atypical case of telangiectatic metastatic breast carcinoma presenting as
      purpura.

PMID- 28752120
TI  - Extrafacial nuchal lupus miliaris disseminatus faciei.

PMID- 28752121
TI  - Docetaxel extravasation: Pathologic correlation and treatment with intralesional
      steroids.

PMID- 28752122
TI  - Cutaneous purpura of Sjogren syndrome successfully treated with
      hydroxychloroquine.

PMID- 28752123
TI  - Topical imiquimod for the palliative treatment of recurrent oral squamous cell
      carcinoma.

PMID- 28752124
TI  - Drug reaction with eosinophilia and systemic symptoms (DRESS) successfully
      treated with tumor necrosis factor-alpha inhibitor.

PMID- 28752125
TI  - Oral warty dyskeratoma of the retromolar trigone: An unusual presentation of a
      rare lesion.

PMID- 28752126
TI  - Adalimumab-associated bullous pemphigoid in a patient with ulcerative colitis.

PMID- 28752127
TI  - Corrigendum to "Recommendations for Diagnosis and Management of Osteoporosis in
      COPD Men".
AB  - [This corrects the article DOI: 10.5402/2011/901416.].

PMID- 28752128
TI  - Dual Kidney Transplantation: A Review of Past and Prospect for Future.
AB  - Kidney transplantation (KT) is one of the treatment options for patients with
      chronic kidney disease. The number of patients waiting for kidney transplantation
      is growing day by day. Various strategies have been put in place to expand the
      donor pool. Extended criteria donors are now accepted more frequently. Increasing
      number of elderly donors with age > 60 years, history of diabetes or
      hypertension, and clinical proteinuria are accepted as donor. Dual kidney
      transplantation (DKT) is also more frequently done and experience with this
      technique is slowly building up. DKT not only helps to reduce the number of
      patients on waiting list but also limits unnecessary discard of viable organs.
      Surgical complications of DKT are comparable to single kidney transplantation
      (SKT). Patient and graft survivals are also promising. This review article
      provides a summary of evidence available in the literature.

PMID- 28752129
TI  - Retracted: Physical Activity: An Important Adaptative Mechanism for Body-Weight
      Control.
AB  - [This retracts the article DOI: 10.5402/2012/675285.].

PMID- 28752130
TI  - Design analysis of an MPI human functional brain scanner.
AB  - MPI's high sensitivity makes it a promising modality for imaging brain function.
      Functional contrast is proposed based on blood SPION concentration changes due to
      Cerebral Blood Volume (CBV) increases during activation, a mechanism utilized in
      fMRI studies. MPI offers the potential for a direct and more sensitive measure of
      SPION concentration, and thus CBV, than fMRI. As such, fMPI could surpass fMRI in
      sensitivity, enhancing the scientific and clinical value of functional imaging.
      As human-sized MPI systems have not been attempted, we assess the technical
      challenges of scaling MPI from rodent to human brain. We use a full-system MPI
      simulator to test arbitrary hardware designs and encoding practices, and we
      examine tradeoffs imposed by constraints that arise when scaling to human size as
      well as safety constraints (PNS and central nervous system stimulation) not
      considered in animal scanners, thereby estimating spatial resolutions and
      sensitivities achievable with current technology. Using a projection FFL MPI
      system, we examine coil hardware options and their implications for sensitivity
      and spatial resolution. We estimate that an fMPI brain scanner is feasible,
      although with reduced sensitivity (20*) and spatial resolution (5*) compared to
      existing rodent systems. Nonetheless, it retains sufficient sensitivity and
      spatial resolution to make it an attractive future instrument for studying the
      human brain; additional technical innovations can result in further improvements.

PMID- 28752131
TI  - Multiple Administrations of Viral Nanoparticles Alter in Vivo Behavior-Insights
      from Intravital Microscopy.
AB  - Multiple administrations of nanoparticle-based formulations are often a clinical
      requirement for drug delivery and diagnostic imaging applications. Steady
      pharmacokinetics of nanoparticles is desirable to achieve efficient therapeutic
      or diagnostic outcomes over such repeat administrations. While clearance through
      mononuclear phagocytic system is a key determinant of nanoparticle persistence in
      vivo, multiple administrations could potentially result in altered
      pharmacokinetics by evoking innate or adaptive immune responses. Plant viral
      nanoparticles (VNPs) represent an emerging class of programmable nanoparticle
      platform technologies that offer a highly organized proteinaceous architecture
      and multivalency for delivery of large payloads of drugs and molecular contrast
      agents. These very structural features also render them susceptible to immune
      recognition and subsequent accelerated systemic clearance that could potentially
      affect overall efficiency. While the biodistribution and pharmacokinetics of VNPs
      have been reported, the biological response following repeat administrations
      remains an understudied area of investigation. Here, we demonstrate that weekly
      administration of filamentous plant viruses results in the generation of
      increasing levels of circulating, carrier-specific IgM and IgG antibodies.
      Furthermore, PVX specific immunoglobulins from the serum of immunized animals
      quickly form aggregates when incubated with PVX in vitro. Such aggregates of VNP
      immune complexes are also observed in the mouse vasculature in vivo following
      repeat injections when imaged in real time using intravital two-photon laser
      scanning microscopy (2P-LSM). The size of aggregates diminishes at later time
      points, coinciding with antibody class switching from IgM to IgG. Together, our
      results highlight the need for careful in vivo assessment of (viral) nanoparticle
      based platform technologies, especially in studying their performance after
      repeat administration. We also demonstrate the utility of intravital microscopy
      to aid in this evaluation.

PMID- 28752132
TI  - Cognitive Support During High-Consequence Episodes of Care in Cardiovascular
      Surgery.
AB  - Despite significant efforts to reduce preventable adverse events in medical
      processes, such events continue to occur at unacceptable rates. This paper
      describes a computer science approach that uses formal process modeling to
      provide situationally aware monitoring and management support to medical
      professionals performing complex processes. These process models represent both
      normative and non-normative situations, and are validated by rigorous automated
      techniques such as model checking and fault tree analysis, in addition to careful
      review by experts. Context-aware Smart Checklists are then generated from the
      models, providing cognitive support during high-consequence surgical episodes.
      The approach is illustrated with a case study in cardiovascular surgery.

PMID- 28752133
TI  - Comparison of recruitment and retention among demographic subgroups in a large
      diverse population study of diet.
AB  - OBJECTIVE: We examined the feasibility of conducting a longitudinal study of diet
      among diverse populations by comparing rates of response throughout recruitment
      and retention phases by demographic and other characteristics. METHODS: Using
      quota sampling, participants were recruited from 3 geographically and
      demographically diverse integrated health systems in the United States. Overall,
      12,860 adults, ages 20-70, were invited to participate via mail. Participation
      first required accessing the study's website and later meeting eligibility
      criteria via telephone interview. Enrollees were asked to provide two 24-hour
      dietary recalls, either interviewer-administered or self-administered on the web,
      over 6 weeks. Stepped monetary incentives were provided. RESULTS: Rates for
      accessing the study website ranged from 6% to 23% (9% overall) across sites. Site
      differences may reflect differences in recruitment strategy or target samples. Of
      those accessing the website, enrollment was high (>= 87%). Of the 1185 enrollees,
      42% were non-Hispanic white, 34% were non-Hispanic black, and 24% were Hispanic.
      Men and minorities had lower enrollment rates than women and non-Hispanic whites,
      partially due to less successful telephone contact for eligibility screening.
      Once enrolled, 90% provided 1 recall and 80% provided both. Women had higher
      retention rates than men, as did older compared to younger participants.
      Retention rates were similar across race/ethnicity groups. CONCLUSIONS: While
      study recruitment remains challenging, once recruited most participants,
      regardless of race/ethnicity, completed two 24-hour dietary recalls, both
      interviewer-administered and self-administered on the web. This study
      demonstrates the feasibility of collecting multiple 24-hour recalls including
      less expensive automated self-administered recalls among diverse populations.

PMID- 28752134
TI  - HIV Infection of Macrophages: Implications for Pathogenesis and Cure.
AB  - Although CD4+ T cells represent the major reservoir of persistent HIV and SIV
      infection, accumulating evidence suggests that macrophages also contribute.
      However, investigations of the role of macrophages are often underrepresented at
      HIV pathogenesis and cure meetings. This was the impetus for a scientific
      workshop dedicated to this area of study, held in Cambridge, MA in January 2017.
      The workshop brought together experts in the fields of HIV/SIV immunology and
      virology, macrophage biology and immunology, and animal models of HIV/SIV
      infection to discuss the role of macrophages as a physiologically relevant viral
      reservoir, and the implications of macrophage infection for HIV pathogenesis and
      strategies for cure. While still controversial, there is an emerging theory that
      infected macrophages likely persist in the setting of combination antiretroviral
      therapy. These macrophages could then drive persistent inflammation and
      contribute to the viral reservoir, which indicates the importance of addressing
      macrophages as well as CD4+ T cells with future therapeutic strategies.

PMID- 28752135
TI  - Nanoscale x-ray imaging of circuit features without wafer etching.
AB  - Modern integrated circuits (ICs) employ a myriad of materials organized at
      nanoscale dimensions, and certain critical tolerances must be met for them to
      function. To understand departures from intended functionality, it is essential
      to examine ICs as manufactured so as to adjust design rules, ideally in a non
      destructive way so that imaged structures can be correlated with electrical
      performance. Electron microscopes can do this on thin regions, or on exposed
      surfaces, but the required processing alters or even destroys functionality.
      Microscopy with multi-keV x-rays provides an alternative approach with greater
      penetration, but the spatial resolution of x-ray imaging lenses has not allowed
      one to see the required detail in the latest generation of ICs. X-ray
      ptychography provides a way to obtain images of ICs without lens-imposed
      resolution limits, with past work delivering 20-40 nm resolution on thinned ICs.
      We describe a simple model for estimating the required exposure, and use it to
      estimate the future potential for this technique. Here we show for the first time
      that this approach can be used to image circuit detail through an unprocessed 300
      MUm thick silicon wafer, with sub-20 nm detail clearly resolved after mechanical
      polishing to 240 MUm thickness was used to eliminate image contrast caused by Si
      wafer surface scratches. By using continuous x-ray scanning, massively parallel
      computation, and a new generation of synchrotron light sources, this should
      enable entire non-etched ICs to be imaged to 10 nm resolution or better while
      maintaining their ability to function in electrical tests.

PMID- 28752136
TI  - Integrating personalized genomics into Turkish healthcare system: A cancer
      oriented pilot activity of Istanbul Northern Anatolian Public Hospitals with
      GLAB.

PMID- 28752137
TI  - Echocardiographic epicardial fat thickness measurement: A new screening test for
      subclinic atherosclerosis in patients with inflammatory bowel diseases.
AB  - OBJECTIVE: Inflammatory bowel diseases (IBD) consist of a number of chronic
      inflammatory diseases. Inflammatory process is known to be involved in all stages
      of atherosclerosis. Early atherosclerosis is reflected by increased levels of
      carotid artery intima media thickness (c-IMT) and high-sensitivity C-reactive
      protein (hs-CRP). Epicardial fat thickness (EFT) strongly influences both the
      formation and progression of atherosclerosis. Recent studies have demonstrated a
      relationship between c-IMT and hs-CRP levels and the risk of atherosclerosis in
      patients with IBD. However, no study has yet compared EFT between patients with
      IBD and the general healthy population. Hence, this study was designed to further
      evaluate whether patients with IBD have higher EFT values with increased c-IMT
      and hs-CRP levels compared to those in the healthy population. METHODS: A total
      of 110 patients with IBD and 105 healthy volunteers were enrolled into this
      study. EFT was evaluated by transthoracic echocardiography. c-IMT levels were
      measured using an ultrasound scanner with a linear probe. The plasma levels of hs
      CRP were measured using a highly sensitive sandwich ELISA technique. RESULTS: The
      hs-CRP and c-IMT levels of patients with IBD were significantly higher than those
      of the control group. The EFT values of patients with IBD were significantly
      higher than those of the control group (0.54+/-0.13 vs. 0.49+/-0.09, p=0.002).
      CONCLUSION: Echocardiographic EFT measurements of patients with IBD were
      significantly higher than those of the normal population, which may be associated
      with an increased subclinical atherosclerosis risk in these patients.

PMID- 28752138
TI  - Is duodenal biopsy appropriate in areas endemic for Helicobacter pylori?
AB  - OBJECTIVE: The primary reason for obtaining duodenal biopsy sample is to diagnose
      celiac disease. Helicobacter pylori (H. pylori) and drug injury are common causes
      of duodenitis. The aim of this retrospective study was to explore effects of H.
      pylori and drugs on duodenal mucosa. METHODS: Duodenal biopsy samples of patients
      who underwent upper gastrointestinal endoscopy (UGIE) between February 2014 and
      December 2014 were retrospectively examined. Clinical symptoms, referral
      indications, endoscopic findings, H. pylori status, and drug history were
      recorded. Duodenal biopsy findings were compared based on presence of H. pylori
      and drug history. RESULTS: Of 2389 patients who underwent UGIE, 206 had duodenal
      biopsy. Eight patients (3.9%) were diagnosed with celiac disease. After excluding
      cases with celiac disease, 76 patients of remaining 198 patients (36.9%) had
      duodenal histopathological abnormality. H. pylori was found in 95 (47.9%)
      patients. Drug usage was less common (42%). Of patients who had histopathological
      duodenitis, 59% were H. pylori-infected. Rate of duodenitis was higher in H.
      pylori (+) group than in H. pylori (-) group (45% vs 27.1%; odds ratio, 2.4; 95%
      confidence interval, 1.3-4.4; p=0.005). There was no difference between groups
      regarding drug use in terms of histopathological duodenitis. CONCLUSION: H.
      pylori is the major contributor to duodenitis in high prevalence regions.
      Serological testing may be more appropriate before performing duodenal biopsy in
      patients with suspected celiac disease.

PMID- 28752139
TI  - Association between serum vitamin B12 level and frailty in older adults.
AB  - OBJECTIVE: Frailty is associated with recurrent falls, fractures, limitation of
      daily living activities, cognitive impairment, increase in hospitalization,
      placement in nursing home, and mortality rate in older adults. Although
      malnutrition is one of the most important etiological factors, role of
      micronutrients is unclear. The aim of this study was to investigate association
      between frailty and vitamin B12, which has been demonstrated to be related to
      numerous geriatric syndromes. METHODS: Total of 335 patients who presented at
      geriatric outpatient clinic and underwent comprehensive geriatric assessment were
      included in this study. All patients were evaluated with both Fatigue,
      Resistance, Ambulation, Illnesses, and Loss of Weight (FRAIL) scale and Fried
      criteria for frailty. Vitamin B12 deficiency was defined as serum vitamin B12
      level of less than 400 pg/mL. RESULTS: In total of 335 patients, 88 (26.3%) were
      assessed as frail, 156 (46.6%) were prefrail, and 91 (27.2%) were robust. When
      the 3 groups were compared, it was found that patients in frail group had highest
      average age and lowest education level (p<0.001) and that complaints of urinary
      incontinence, balance disorders, recurrent falls, sleep disorders, amnesia,
      chronic pain, and constipation were more frequent in this group (p<0.05). Albumin
      and 25-hydroxy vitamin D levels decreased as frailty level increased (p<0.05),
      but no association between vitamin B12 levels and frailty was found. Patients
      were divided into 2 groups: vitamin B12 level above and below 400 pg/mL. Groups
      were then compared in terms of subparameters of both the FRAIL and Fried
      criteria, and no significant difference between groups was found (p>0.05).
      CONCLUSION: Results of this study determined no association between vitamin B12
      level and frailty in geriatric population; however, longitudinal studies are
      needed to clarify relationship.

PMID- 28752140
TI  - The effects of training inpatients and their relatives about infection control
      measures and subsequent rate of infection.
AB  - OBJECTIVE: Healthcare-associated infections are one of the most important
      problems of all health institutions. This study was conducted to evaluate results
      of training about infection control measures provided to patients treated and
      hospitalized in clinics of obstetrics and gynecology, and to their relatives, as
      well as subsequent effect on infection rate. METHODS: The study was conducted in
      clinics of obstetrics and gynecology of a state hospital. Study group comprised
      midwives and nursing staff, and inpatients and their relatives. Survey made up of
      16 questions was administered to patients and relatives before and after training
      provided by infection nurses. Survey with 18 questions was administered to
      midwives/nurses to evaluate compliance of patients and relatives with infection
      control measures. Study data were analyzed using statistical analysis software
      and findings were evaluated as numbers and percentages using Student's t-test.
      RESULTS: According to survey of patients and relatives, mean knowledge level
      score before and after training was 20.07+/-46.76 and 96.36+/-11.85,
      respectively. Results indicated that training about infection control measures
      was effective at increasing knowledge level and compliance of patients and their
      relatives (p<0.05). Of the total, 87.5% of midwives/nurses stated that educating
      patients and relatives about infection control measures facilitated treatment and
      healthcare processes. In all, 95.9% of midwives/nurses thought that such
      education contributed to observance of infection control measures by patients and
      relatives. CONCLUSION: It is thought that regular education about infection
      control measures provided to patients and relatives would have positive effect
      and reduce incidence rate of healthcare-associated infection.

PMID- 28752141
TI  - Neutrophil gelatinase-associated lipocalin reflects the severity of anemia
      without iron deficiency and secondary hyperparathyroidism in hemodialysis
      patients.
AB  - OBJECTIVE: Secondary hyperparathyroidism (SHPT) and anemia are the primary and
      most common complications in patients receiving hemodialysis (HD). Neutrophil
      gelatinase-associated lipocalin (NGAL) is a new marker to assess iron deficiency
      and manage iron therapy for HD patients. The aim of this study was to determine
      any association between serum NGAL level and anemia without iron deficiency in
      patients with SHPT on chronic HD. METHODS: Total of 61 SHPT patients on chronic
      HD were enrolled in the study and divided into 3 groups: mild SHPT group (n=17),
      moderate SHPT group (n=21), and severe SHPT group (n=23). Hemogram, biochemical
      assays, and level of ferritin, high sensitivity C-reactive protein (hs-CRP), and
      NGAL were evaluated in all groups. RESULTS: Serum NGAL level was significantly
      higher and hemoglobin (Hb) level was significantly lower in severe SHPT patients
      compared with both mild and moderate SHPT patients. Furthermore, in severe SHPT
      group, serum NGAL level was significantly positively correlated with serum
      parathyroid hormone (r=0.79; p=0.00) and hs-CRP (r=0.52; p=0.01) level and
      negatively correlated with serum Hb (r=-0.56; p=0.00) level. CONCLUSION: SHPT was
      important factor affecting anemia in HD patients. Even when iron deficiency
      anemia is excluded in patients with SHPT, there was significant negative
      correlation between serum NGAL and Hb.

PMID- 28752142
TI  - Clinical features of the patient with multiple primary tumors: Single center
      experience.
AB  - OBJECTIVE: Multiple primary tumors are the ones that develop in the same patient
      at the same or different times. They are usually examined under two groups. If
      the second tumor is diagnosed 6 months after the first tumor is diagnosed, it is
      named as metachronous tumor. If it is diagnosed in 6 months after the first
      diagnosis, it is called as synchronous tumor. The malignancy of tumors should be
      proved histologically. At least 2 cm of solid tissue should be present between
      two tumors. If they are at localized at the same place, a gap of at least 5 years
      should be present between them. Metastatic disease should be eliminated. This
      study aimedto review the clinical, demographic, and pathological features of
      multiple primary tumors, detect the prevalence, compare the results with
      literature findings, and evaluate and improve the approach to multiple primary
      tumors. METHODS: A total of 170 patients diagnosed with multiple primary tumors
      were included in this study. Patient data were obtained from pathology and
      medical reports of the patients. RESULTS: Most of the multiple primary tumors
      were metachronous. The number of male patients was more than that of female
      patients. The median time between double tumors was 3 monthsforsynchronous
      tumorsand 26 months for metachronous tumors. Synchronous tumors with the highest
      prevalence of comorbidity were lung-larynx and lung-colon, whereas metachronous
      tumors with the highest prevalence of comorbidity were lung-bladder, lung-larynx,
      breast-endometrium, and breast-colon. The history of smoking and alcohol was
      found to be higher in male patients andsynchronous tumors. CONCLUSION: The
      detection of the first tumor in the metastatic stage and an accompanying
      synchronous secondary tumor was found to be a poor prognostic factor. The
      treatment of the first tumor, smoking, squamous cell histology, and male gender
      were among the other factors negatively affecting survival, although they were
      not statistically significant.

PMID- 28752143
TI  - The effects of pre-obesity on quality of life, disease activity, and functional
      status in patients with ankylosing spondylitis.
AB  - OBJECTIVE: This study was an investigation of effects of pre-obesity on clinical
      characteristics and quality of life in patients with ankylosing spondylitis (AS).
      METHODS: Total of 28 AS patients and 30 age- and sex-matched healthy controls
      were included in the study. Patients and controls with any systemic inflammatory
      disease and/or cognitive and mental problems were excluded. Disease activity and
      functional capacity were measured using the Bath Ankylosing Spondylitis Disease
      Activity Index and Bath Ankylosing Spondylitis Functional Index. For quality of
      life assessment, 36-Item Short Form Health Survey was used in both groups, and AS
      group also responded to Ankylosing Spondylitis Quality of Life questionnaire.
      RESULTS: There was no significant difference in sociodemographic characteristics
      between AS patients and healthy controls (p>0.05). Mean quality of life scores
      were significantly lower in the pre-obese AS patients compared with controls
      (p<0.05). Functional capacity was positively and significantly associated with
      body mass index (BMI) (p=0.024) and disease activity was significantly associated
      with female gender (p=0.011). CONCLUSION: Increased BMI in patients with AS is
      factor that affects quality of life, disease activity, and functional capacity.
      Multidisciplinary rehabilitation programs will support improved quality of life
      for pre-obese patients with AS.

PMID- 28752144
TI  - Is there any relationship between low PAPP-A levels and measures of umbilical
      vein and placental thickness during first trimester of pregnancy?
AB  - OBJECTIVE: Low pregnancy-associated plasma protein A (PAPP-A) level is associated
      with adverse perinatal outcomes. The purpose of this study was to evaluate
      relationship between umbilical cord diameter (UCD), umbilical vein and artery
      diameters (UVD, UAD), placental thickness, and PAPP-A level at gestational age of
      between 11 and 14 weeks. METHODS: UCD, UVD, UAD, and placental thickness of 246
      women were assessed during ultrasound examination at between 11 and 14 weeks of
      gestation, as well as measurement of nuchal translucency (NT) and crown-rump
      length (CRL). Patients were divided into 2 groups according to PAPP-A percentile.
      Group 1 comprised 23 patients who had low PAPP-A (<0.44 multiple of medians
      [MoM], <10th percentile) and Group 2 was made up of 223 patients with PAPP-A of
      >0.44 MoM, >10th percentile. Calipers used for measurement were placed inner edge
      to inner edge of echogenic boundaries of the vessel. Largest sections of all
      vessels (UV and both arteries) were evaluated. Thickest part of the placenta was
      used for placental thickness measurement. RESULTS: Narrow UCD (<4.5+/-0.6 mm) was
      associated with low PAPP-A level (p=0.02). There was no significant difference in
      UVD, UAD, or placental thickness between groups. There was no significant
      difference in gestational age, CRL, or NT between groups. Fetal birth weight was
      significantly lower in Group 1 (p=0.03). CONCLUSION: Closer attention to women
      with low-risk, healthy pregnancies and low PAPP-A level in first trimester
      screening results is recommended. They should be routinely screened for
      background medical risk factors and umbilical cord morphology in first trimester
      scan.

PMID- 28752145
TI  - Increased levels of red cell distribution width is correlated with presence of
      left atrial stasis in patients with non-valvular atrial fibrillation.
AB  - OBJECTIVE: Red cell distribution width (RDW) and neutrophil to lymphocyte ratio
      (NLR) have been found to be associated with non-valvular atrial fibrillation (AF)
      and cardiovascular diseases. However, correlation of these parameters with
      presence of left atrial (LA) thrombus and/or spontaneous echo contrast (SEC) in
      patients with non-valvular AF has not been clarified. This study was an
      investigation of correlation of RDW, NLR, and clinical risk factors with LA
      thrombus and dense SEC in patients with non-valvular AF in the Turkish
      population. METHODS: The demographic, laboratory, and echocardiographic
      properties of 619 non-valvular AF patients who underwent transesophageal
      echocardiography (TEE) examination before direct current cardioversion (DCCV) or
      AF ablation treatment were retrospectively investigated. Complete blood count
      (CBC) and biochemical parameters were studied 6 to 12 hours before TEE
      examination. Left atrial stasis (LAS) markers were noted as presence of left
      atrial/left atrial appendage (LA/LAA) thrombus or dense spontaneous echo contrast
      (DSEC). RESULTS: Total of 325 (52%) patients with LAS were compared with 294
      patients (48%) without LAS. In the LAS group, there were 274 (84%) patients with
      LA/LAA thrombus and 51 (16%) patients with DSEC. LAS (+) group, values for RDW
      (14.85+/-1.48 vs. 13.77+/-1.30; p<0.01), NLR (2.38 [1.58], vs. 2.10 [1.35];
      p<0.01) and C-reactive protein (0.95 [0.61] vs. 0.88 [0.60] mg/L; p<0.01) were
      significantly higher than seen in LAS (-) group. In multivariate regression
      analysis, increased level of RDW, age, male gender, heart failure, duration of AF
      >6 months, and international normalized ratio <2 were independently correlated
      with presence of LAS. CONCLUSION: Our study indicated that increased level of RDW
      is independently correlated with higher risk for development of LAS in patients
      with non-valvular AF.

PMID- 28752146
TI  - Acute biliary pancreatitis in cholecystectomised patients.
AB  - OBJECTIVE: The present study is an evaluation of cases of acute biliary
      pancreatitis that developed subsequent to cholecystectomy. METHODS: Total of 44
      patients were assessed in this retrospective study. Demographic characteristics,
      severity of illness, time elapsed between cholecystectomy and development of
      pancreatitis, whether endoscopic sphincterotomy (ES) was performed, surgical
      procedure used, duration of hospitalization, and mortality data were recorded.
      RESULTS: Mean age of all patients was 60.14+/-16.4 years (range: 20-85 years),
      and female:male ratio was 28:16. Mean length of time elapsed between
      cholecystectomy and development of acute pancreatitis was 80.6 months (range: 5
      230 months). Gallstones and biliary sand were found in the choledochi of 36
      patients upon endoscopic retrograde cholangiopancreatography (ERCP), but not
      observed in the remaining 8 patients. ES was performed and material was extracted
      in 32 of the 36 patients, but stone extraction was unsuccessful in 4 cases; 3
      patients underwent open surgery with choledochus exploration and 1 patient died.
      Excluding this patient, mean duration of hospitalization was 7.5+/-2.5 days.
      CONCLUSION: Stones in bile ducts may remain asymptomatic for long periods after
      cholecystectomy. However, some stones trigger acute pancreatitis months or years
      after cholecystectomy, causing risk of mortality. ERCP and ES are the standard
      treatments. If these are unsuccessful, the choledochus may be explored via open
      or laparoscopic surgery.

PMID- 28752147
TI  - Giant neglected Bowen's disease lesion treated successfully with topical 5
      fluorouracil.

PMID- 28752148
TI  - A condition that should be kept in mind in incarcerated hernia: Amyand's hernia.
AB  - As a complication of inguinal hernia, incarcerations are often seen in emergency
      services. Incarceration is an acute complication of inguinal hernia presenting as
      surgical emergency. The sac of inguinal hernia most frequently contains omentum
      and intestine but sometimes organs such as appendix and Meckel's diverticulum can
      also be seen in the hernial sac. We present a case of Amyand's hernia containing
      appendix in the incarcerated herniated sac.

PMID- 28752149
TI  - Systemic juvenile idiopathic arthritis as a fever of unknown origin.
AB  - Juvenile idiopathic arthritis (JIA) is a rare inflammation with still
      unidentified cause. It can also be cause of fever of unknown origin. Diagnosis is
      made by eliminating infection, malignancy, and rheumatological diseases. In this
      report, case of a 5-year-old patient with symptoms of intermittent fever, areas
      of rash on the body, itching, and swelling, redness, and pain in the right and
      left ankle is described. Serological test results were negative for infectious
      agents, and malignancy was excluded. Patient was diagnosed with systemic JIA
      associated with intermittent fever, negative rheumatological markers and negative
      serology test results. Treatment with methylprednisolone and methotrexate yielded
      positive clinical response. Diagnosis of systemic JIA can be challenging, and
      must be made by eliminating other diseases.

PMID- 28752150
TI  - Priapism associated with the addition of risperidone to methylphenidate
      monotherapy: a case report.
AB  - Priapism is a state of prolonged and unwanted erection without sexual stimulation
      or desire. Priapism may occur with a variety of diseases or as a side effect of
      medication. Immediate diagnosis and treatment is essential, as ischemia of
      cavernous tissues results in erectile dysfunction. Described in the present
      report is a 12-year-old male with priapism associated with the addition of
      risperidone to methylphenidate monotherapy. Priapism decreased and disappeared
      following discontinuation of drug therapy and implementation of cavernous
      drainage. To our knowledge, the present is the first report to describe priapism
      associated with the addition of risperidone to methylphenidate monotherapy. It is
      hoped that attention will be drawn to the risk of priapism caused by the
      combination of these psychopharmacologic agents.

PMID- 28752151
TI  - Intra-articular lipoma of the knee joint located in the posterior compartment: A
      rare location.
AB  - This report presents the case of a 51-year-old woman with intermittent left knee
      pain, especially during full flexion of the knee, which had been ongoing for 1
      year. Magnetic resonance imaging (MRI) showed mild effusion and round mass at the
      posterior compartment without synovial changes. Computerized tomography (CT)
      indicated mass had homogeneous low attenuation and density measurement of -99.4+/
      62.3 Hounsfield units (HU), correlated with a lipomatous lesion.

PMID- 28752152
TI  - Foreign bodies in the rectum: 2 Case reports.
AB  - Encountering a foreign object in the rectum is rare; however, the incidence has
      greatly increased in recent years. Treatment of these patients requires a
      multidisciplinary approach because this condition may have serious complications.
      Presently described is management of 2 cases of rectal foreign body treated in
      the clinic.

PMID- 28752153
TI  - Iatrogenic Cushing's syndrome caused by intranasal steroid use.
AB  - Cushing's syndrome (CS) is common after oral steroid use and has also been
      reported following topical or inhaled use, but it is extremely uncommon after
      intranasal administration. This is the case of a 6-year-old child who developed
      Cushing's syndrome after intranasal application of dexamethasone sodium phosphate
      for a period of 6 months. Pediatricians and other clinical practitioners should
      be aware that high-dose and long-term nasal steroid administration may cause
      iatrogenic Cushing's syndrome characterized by complications of glucocorticoid
      excess as well as serious and even life-threatening complications of adrenal
      insufficiency.

PMID- 28752154
TI  - Epidemiology, pathophysiology, clinical evaluation, and treatment of carbon
      monoxide poisoning in child, infant, and fetus.
AB  - Carbon monoxide (CO) poisoning is one of the most common types of poisoning
      causing death worldwide. In our country, it occurs particularly during winter as
      a result of leak from stove or water heater, or as result of inhalation during a
      fire. Although most poisonings occur accidentally, some cases are suicide
      attempt. As CO is a substance that is not visible and has no taste or smell and
      is therefore difficult to detect, the gas can be a "silent killer" that is not
      noticed until effects develop. CO reacts with oxygen, creating carboxy hemoglobin
      (COHb), which leads to tissue hypoxia. In addition, it has direct effect of
      causing cellular damage. Although symptoms of acute poisoning are most commonly
      observed in patients admitted to emergency rooms, effects of chronic exposure to
      CO can also seen. Clinically, although it affects all organ systems, involvement
      of central nervous system (CNS) and cardiovascular system is predominant. Most
      common poisoning symptoms are weakness, dizziness, headache, nausea, and
      nonspecific flu-like symptoms, like vomiting. Depending on severity of exposure,
      seizures, syncope, and arrhythmia may also be observed. In pregnant women, fetus
      can be harmed with relatively low level of COHb. Poisoning in infants has a more
      severe course than seen in other age groups. Symptoms must be associated with
      cause of poisoning, and careful anamnesis and treatment must be conducted
      quickly. Oxygen is the antidote for CO. It is administered through a mask in the
      form of normobaric oxygen therapy or through specific devices in the form of
      hyperbaric oxygen therapy. In this review, clinical data and current diagnostic
      and therapeutic approaches concerning CO poisoning are discussed.

PMID- 28752155
TI  - Treating Suicidality in College Counseling Centers: A Response to Polychronis.
AB  - This is a commentary on the article by Paul D. Polychronis, "Changes Across Three
      Editions of The Suicidal Patient: Clinical and Legal Standards of Care: Relevance
      to Counseling Centers," published in this issue of the Journal of College Student
      Psychotherapy.

PMID- 28752156
TI  - Accounting for the Confound of Meninges in Segmenting Entorhinal and Perirhinal
      Cortices in T1-Weighted MRI.
AB  - Quantification of medial temporal lobe (MTL) cortices, including entorhinal
      cortex (ERC) and perirhinal cortex (PRC), from in vivo MRI is desirable for
      studying the human memory system as well as in early diagnosis and monitoring of
      Alzheimer's disease. However, ERC and PRC are commonly over-segmented in T1
      weighted (T1w) MRI because of the adjacent meninges that have similar intensity
      to gray matter in T1 contrast. This introduces errors in the quantification and
      could potentially confound imaging studies of ERC/PRC. In this paper, we propose
      to segment MTL cortices along with the adjacent meninges in T1w MRI using an
      established multi-atlas segmentation framework together with super-resolution
      technique. Experimental results comparing the proposed pipeline with existing
      pipelines support the notion that a large portion of meninges is segmented as
      gray matter by existing algorithms but not by our algorithm. Cross-validation
      experiments demonstrate promising segmentation accuracy. Further, agreement
      between the volume and thickness measures from the proposed pipeline and those
      from the manual segmentations increase dramatically as a result of accounting for
      the confound of meninges. Evaluated in the context of group discrimination
      between patients with amnestic mild cognitive impairment and normal controls, the
      proposed pipeline generates more biologically plausible results and improves the
      statistical power in discriminating groups in absolute terms comparing to other
      techniques using T1w MRI. Although the performance of the proposed pipeline is
      inferior to that using T2-weighted MRI, which is optimized to image MTL sub
      structures, the proposed pipeline could still provide important utilities in
      analyzing many existing large datasets that only have T1w MRI available.

PMID- 28752157
TI  - Retention Rate of Four Different Sealant Materials after Four Years.
AB  - PURPOSE: To test the hypotheses: 1) cumulative survival rates of fully and
      partially retained high-viscosity glass-ionomer (HVGIC) ART sealants with heat
      application and glass-carbomer sealants on occlusal and free-smooth surfaces are
      both higher than that of resin sealants; 2) cumulative survival rate of fully and
      partially retained high-viscosity glass-ionomer ART sealant with heat application
      on occlusal and free-smooth surfaces is higher than that of comparable ART
      sealants without heat application. MATERIALS AND METHODS: The block-randomised
      clinical trial covered 405 eight-year-old children. The HVGIC was Ketac Molar
      Easymix, the glass carbomer was GlassCarbomer and the resin sealant was Clinpro.
      Retention rates of sealants on occlusal and free-smooth surfaces using
      conventional and modified categorisation (fully and partially retained sealants
      vs those completely lost [at least one-third of surface re-exposed]) were the
      dependent variables. The Kaplan-Meier survival method was used. RESULTS: The
      cumulative survival rate of completely and partially retained resin sealants on
      occlusal (81.2%) and free-smooth (81%) surfaces after 4 years was statistically
      significantly higher, and that of glass-carbomer sealants (10.8% and 21.1%,
      respectively) was statistically significantly lower than those of the other
      sealant groups. There was no statistically significant difference in survival
      rates of completely and partially retained high-viscosity glass-ionomer ART
      sealants with (56% for both surfaces) or without heat application (56%) on
      occlusal and free-smooth surfaces (55.7% and 59.1%, respectively). CONCLUSIONS:
      Resin sealants had the highest and glass-carbomer sealants the lowest retention
      rate after 4 years. Application of heat to high-viscosity glass-ionomer ART
      sealants did not result in a significantly higher sealant retention rate. Use of
      the modified categorisation for determining sealant retention is advocated.

PMID- 28752158
TI  - Contextual Social Inequities and Occurrence of Dental Caries in Adolescents: A
      Systematic Review.
AB  - PURPOSE: This systematic review sought to determine whether there is consistent
      evidence of the association between contextual social inequities and the
      occurrence of dental caries in adolescents. MATERIALS AND METHODS: An electronic
      survey in ISI Web of Science, SCOPUS, MEDLINE, LILACS, Cochrane Library, and
      SciELO databases was performed, establishing a specific search strategy in each
      of them. Only analytical articles in which social indicators were measured at the
      contextual level published up to December 2015 were included. The risk of bias of
      studies selected was assessed from parameters suggested by MOOSE (Meta-analysis
      of Observational Studies in Epidemiology), classifying them in each item as
      adequate, partially adequate, inadequate and unclear. After evaluation, studies
      were classified as good (level 1), regular (level 2) or bad (level 3) quality.
      RESULTS: Of the 181 articles identified, four met the inclusion and exclusion
      criteria, and of these, only one showed high risk of bias. Four articles showed
      significant association between contextual socioeconomic factors and caries.
      Despite the measurement of different social inequities such as social class and
      neighbourhood empowerment level, the articles showed significant association
      between contextual socioeconomic factors and caries. CONCLUSIONS: The scientific
      evidence that adolescents from areas of higher social inequity are at higher risk
      for caries is weak, especially considering the small number of existing studies,
      methodological vulnerabilities and the risk of study bias.

PMID- 28752159
TI  - Oral Health Behaviour and Oral Hygiene of Dental Professionals and Laypersons - A
      Survey Performed in Lower Saxony, Germany.
AB  - PURPOSE: The aim of this survey-based cross-sectional study was to analyse the
      oral health behaviour of dental professionals and persons without professional
      dental knowledge (layperson group) regarding the use and selection of tools for
      their personal dental hygiene. MATERIALS AND METHODS: A total of 356 persons
      participated in the survey (dental professional group: 160; layperson group:
      196). Information regarding dental hygiene habits, such as toothbrush use,
      toothbrushing habits, and the use of additional dental hygiene tools was
      determined using a standardised questionnaire. Data were analysed using the chi
      squared and Wilcoxon tests, with significance set at p < 0.05. RESULTS: 93% of
      the dental professional group and 89% of layperson group used manual toothbrushes
      (p = 0.03). Power toothbrushes were used by 57% of those surveyed in the dental
      professional group and 37% of those in the layperson group (p < 0.01). In the
      dental professional group, the duration of toothbrushing was significantly longer
      and it was performed more often compared to layperson group (p < 0.001). The use
      of dental floss and interdental brushes in the layperson group (dental floss 38%,
      interdental brush 5%) was considerably lower than in the dental professional
      group (dental floss 84%, interdental brush 11%; p < 0.001). CONCLUSION: The
      results of the survey on oral health behaviour revealed significant differences
      between the groups. The acceptance of additional tools for personal dental
      hygiene was low, such as dental floss and interdental brushes. Given the great
      importance of these tools for biofilm control, they should be emphasised in
      motivational measures and instructions regarding oral care performed at home.

PMID- 28752160
TI  - Saliva, Serum Levels of Interleukin-21, -33 and Prostaglandin E2 in Patients with
      Generalised Aggressive or Chronic Periodontitis.
AB  - PURPOSE: This cross-sectional study aims to evaluate saliva, serum levels of
      interleukin-21 (IL-21), IL-33, and prostaglandin E2 (PGE2) in patients with
      generalised chronic periodontitis or aggressive periodontitis. MATERIALS AND
      METHODS: Before initiation of any periodontal treatment, saliva and serum samples
      were collected and clinical periodontal measurements were recorded from 94
      participants (25 aggressive periodontitis patients, 25 chronic periodontitis
      patients, 44 periodontally healthy individuals). IL-21, IL-33 and PGE2 levels in
      serum and saliva samples were determined by ELISA. Data were tested statistically
      using Kruskal-Wallis, Mann-Whitney U-, and Spearman-rho rank tests. RESULTS:
      Saliva IL-33 levels were statistically significantly higher in the chronic than
      the aggressive group (p < 0.05). Serum IL-33, saliva and serum IL-21 and PGE2
      levels were similar in the two periodontitis groups. Saliva IL-33 levels
      correlated with age in the chronic periodontitis group (p < 0.05). Statistically
      significant positive correlations were found between serum, saliva PGE2 levels
      and plaque index (p < 0.05). IL-33 and IL-21 levels in serum samples positively
      correlated in the periodontitis groups (p < 0.05). CONCLUSION: IL-21 and PGE2
      analysis did not exhibit discriminating data between generalised chronic and
      aggressive periodontitis, but the present findings support the role of these
      cytokines in periodontitis. Statistically significantly higher saliva IL-33
      levels in the chronic periodontitis group warrant further research.

PMID- 28752161
TI  - Oral healthcare in rural areas.

PMID- 28752162
TI  - An aryne-based three-component access to alpha-aroylamino amides.
AB  - Aryne chemistry has recently received widespread attention and isocyanides have
      been reported as efficient nucleophilic partners in a set of multicomponent
      transformations. In this study, we demonstrate that tertiary alpha
      monosubstituted alpha-isocyanoacetamides are efficaciously coupled with water and
      benzyne to offer a direct and metal-free access to densely functionalized alpha
      benzoylamino amides, without competing with the intramolecular cyclization to 5
      aminooxazoles. Despite the formation of the aryl anion as a key intermediate, the
      reaction displays a stereoconservative course, allowing for the preparation of
      enantiomerically pure alpha-benzoylamino amides. Finally, the synthetic utility
      of the reported MCR was exemplified by the preparation of proglumide, a
      cholecystokinin antagonist.

PMID- 28752163
TI  - 2,5-Hexanedione induces autophagic death of VSC4.1 cells via a PI3K/Akt/mTOR
      pathway.
AB  - 2,5-Hexanedione (HD) is an important bioactive metabolite of n-hexane, which
      mediates the neurotoxicity of the parent compound. Increasing evidence suggests
      that over-activated autophagy can lead to autophagic neuronal death; however,
      whether the excessive autophagy is involved in HD-induced neurotoxicity remains
      unknown. To investigate the effect of HD on autophagy and to find its underlying
      mechanism, we respectively treated VSC4.1 cells with 5, 15 and 25 mM HD for 24 h.
      Our results show that HD induced excessive autophagy of VSC4.1 cells in a dose
      dependent manner, also, the over-activated autophagy was significantly mitigated
      in the presence of PI3K activator or Akt activator or mTOR activator. These
      results indicate that HD induces excessive autophagy of VSC4.1 cells by
      repressing the PI3K/Akt/mTOR signaling pathway. LDH assay showed that HD
      contributed to a concentration dependent increase in VSC4.1 cell death, which was
      significantly reduced by the administration of PIK-III, an autophagy inhibitor.
      These results also indicate that HD induces autophagic death of VSC4.1 cells via
      the signaling pathway.

PMID- 28752164
TI  - In situ generation of human brain organoids on a micropillar array.
AB  - Brain organoids derived from human induced pluripotent stem cells can
      recapitulate the early stages of brain development, representing a powerful in
      vitro system for modeling brain development and diseases. However, the existing
      methods for brain organoid formation often require time-consuming procedures,
      including the initial formation of embryoid bodies (EBs) from hiPSCs, and
      subsequent neural induction and differentiation companied by multi-steps of cell
      transfer and encapsulation in a 3D matrix. Herein, we propose a simple strategy
      to enable in situ formation of massive brain organoids from hiPSCs on a
      micropillar array without tedious manual procedures. The optimized micropillar
      configurations allow for controlled EB formation, neural induction and
      differentiation, and generation of functional human brain organoids in 3D culture
      on a single device. The generated brain organoids were examined to imitate brain
      organogenesis in vivo at early stages of gestation with specific features of
      neuronal differentiation, brain regionalization, and cortical organization. By
      combining microfabrication techniques with stem cells and developmental biology
      principles, the proposed method can greatly simplify brain organoid formation
      protocols as compared to conventional methods, overcoming the potential
      limitations of cell contamination, lower throughput and variance of organoid
      morphology. It can also provide a useful platform for the engineering of stem
      cell organoids with improved functions and extending their applications in
      developmental biology, drug testing and disease modeling.

PMID- 28752165
TI  - Structural and dynamic properties of the C-terminal region of the Escherichia
      coli RNA chaperone Hfq: integrative experimental and computational studies.
AB  - In Escherichia coli, hexameric Hfq is an important RNA chaperone that facilitates
      small RNA-mediated post-transcriptional regulation. The Hfq monomer consists of
      an evolutionarily conserved Sm domain (residues 1-65) and a flexible C-terminal
      region (residues 66-102). It has been recognized that the existence of the C
      terminal region is important for the function of Hfq, but its detailed structural
      and dynamic properties remain elusive due to its disordered nature. In this work,
      using integrative experimental techniques, such as nuclear magnetic resonance
      spectroscopy and small-angle X-ray scattering, as well as multi-scale
      computational simulations, new insights into the structure and dynamics of the C
      terminal region in the context of the Hfq hexamer are provided. Although the C
      terminal region is intrinsically disordered, some residues (83-86) are motionally
      restricted. The hexameric core may affect the secondary structure propensity of
      the C-terminal region, due to transient interactions between them. The residues
      at the rim and the proximal side of the core have significantly more transient
      contacts with the C-terminal region than those residues at the distal side, which
      may facilitate the function of the C-terminal region in the release of double
      stranded RNAs and the cycling of small non-coding RNAs. Structure ensembles
      constructed by fitting the experimental data also support that the C-terminal
      region prefers to locate at the proximal side. From multi-scale simulations, we
      propose that the C-terminal region may play a dual role of steric effect
      (especially at the proximal side) and recruitment (at the both sides) in the
      binding process of RNA substrates. Interestingly, we have found that these
      motionally restricted residues may serve as important binding sites for the
      incoming RNAs that is probably driven by favorable electrostatic interactions.
      These integrative studies may aid in our understanding of the functional role of
      the C-terminal region of Hfq.

PMID- 28752166
TI  - Discovery of 2-(pyridin-2-yl)aniline as a directing group for the sp2 C-H bond
      amination mediated by cupric acetate.
AB  - 2-(Pyridin-2-yl) aniline was designed as a new, removable directing group in
      promoting C-H amination mediated by cupric acetate. Employing this auxiliary, the
      beta-C(sp2)-H bonds of benzamide derivatives can be effectively aminated with a
      variety of amines in moderate to good yields with good functional group tolerance
      in air. In addition, the quinazolinone derivatives were isolated from the
      reaction mixture of N-(2-(pyridin-2-yl)phenyl)benzamide with formamide or 5
      nitroindole. The corresponding mechanism is discussed. These results indicate
      that 2-(pyridine-2-yl)aniline can serve as a directing group.

PMID- 28752167
TI  - A novel enzymatic method for synthesis of glycopeptides carrying natural
      eukaryotic N-glycans.
AB  - A novel enzymatic approach was developed for facile production of glycopeptides
      carrying natural eukaryotic N-glycans. In this approach, peptides can be
      GlcNAcylated at one or two natural N-glycosylation sites via two-step enzymatic
      reactions catalyzed by an evolved N-glycosyltransferase (ApNGTQ469A) and a
      glucosamine N-acetyltransferase (GlmA), respectively. The resulting GlcNAc
      peptides were further modified by an endo-beta-N-acetylglucosaminidase M mutant
      (EndoMN175Q) to generate glycopeptides. In three steps of enzymatic catalysis,
      glycopeptides carrying complex-type N-glycans can be efficiently synthesized.

PMID- 28752168
TI  - Influence of microenvironment topography and stiffness on the mechanics and
      motility of normal and cancer renal cells.
AB  - The tumor microenvironment highly influences cancer cell modes and dynamics,
      above all during invasive and metastatic processes. When aiming at studying
      cancer cell behavior in vitro, the use of conventional cell culture systems, such
      as Petri dishes, fails in recapitulating the mechanical and topographical
      properties of the natural extracellular matrix (ECM). Here the versatility of
      stiffness-tunable hydrogels and the efficacy of the replica molding technique
      with silicone polymers are exploited, aiming at studying cancer and normal cell
      behavior with platforms able to capture the heterogeneities of the natural in
      vivo context. We compared the mechanical properties of normal and cancer renal
      cells on different stiffness value gels (with Young's moduli of 3, 17 and 31 kPa)
      by using atomic force microscopy (AFM) and investigated cell indentation
      phenomena on compliant gels with confocal microscopy. Moreover, we studied cell
      mechanics, morphology and migration on isotropic linear structures, spaced at 1.5
      MUm, aiming at mimicking the aligned fiber bundles typically observed at tumor
      borders. By using this approach, we could highlight differences in the way
      healthy and cancer renal cells react to changes in their microenvironment. Our
      results may potentially pave the way to unravel the complex processes involved in
      cancer progression, especially in tissue invasion and migration during metastasis
      formation.

PMID- 28752169
TI  - Intramolecular ipso-arylative cyclization of aryl-alkynoates and N
      arylpropiolamides with aryldiazonium salts through merged gold/visible light
      photoredox catalysis.
AB  - A visible-light-promoted merged gold/photoredox catalyzed ipso-arylative
      cyclization has been reported. For instance, the reaction of aryl-alkynoates and
      N-arylpropiolamides with aryldiazonium salts in the presence of catalytic amounts
      of [(4-OCH3)C6H4]3PAuCl and Ru(bpy)3(PF6)2 under irradiation using a 32 W CFL
      bulb gave arylated spirocarbocycles in moderate to good yields.

PMID- 28752170
TI  - A green route to methyl acrylate and acrylic acid by an aldol condensation
      reaction over H-ZSM-35 zeolite catalysts.
AB  - A one-step aldol condensation reaction to produce MA and AA is a green and
      promising strategy. Here, the aldol condensation reaction was first conducted
      with DMM and MAc over different types of zeolite catalysts. The H-ZSM-35 zeolite
      demonstrates excellent catalytic performance with a DMM conversion of 100% and a
      MA + AA selectivity of up to 86.2% and superior regeneration ability, with great
      potential for industrial operation.

PMID- 28752171
TI  - Polypyrrole capacitance characteristics with different doping ions and
      thicknesses.
AB  - Polypyrrole films doped with Cl-, SO42- and 4-toluene sulfonic ions (PPy/Cl-,
      PPy/SO42-, PPy/Ts-) with different polymerization charges were prepared by
      electrochemical polymerization. PPy/Ts- films exhibited good electrochemical
      properties when their polymerization charges were 0.5 C cm-2 and 1 C cm-2.
      However, PPy/Cl- and PPy/SO42- films exhibited markedly larger specific
      capacitance than those of PPy/Ts- films when their polymerization charges
      increased to 2 C cm-2 or 4 C cm-2. A simple model was suggested for explaining
      the relation between the electrochemical properties and thickness of the PPy
      films. According to the model, the incremental polymerization bulk of PPy/Ts-
      films from 1 C cm-2 to 2 C cm-2 is "inactive", which resulted in the reduction of
      the specific capacitance by half. X-ray diffraction patterns indicated that
      PPy/Ts- films possessed a more ordered structure, which limited ion diffusion in
      the PPy matrix. Therefore, the high crystallinity of the PPy film does not always
      mean good capacitance properties. In the cycle stability test, the PPy/Ts- film
      exhibited better stability, which should be closely related to its more ordered
      structure. It is noteworthy that we present a newly developed method to estimate
      the appropriate thickness of electrode materials, which is significant in the
      preparation of energy-storage devices.

PMID- 28752172
TI  - A co-pillar[5]arene sensor for linear biogenic amines.
AB  - A thiolated co-pillar[5]arene was attached to the surface of a gold electrode and
      shown to give an analyte-selective voltammetric response to linear biogenic
      amines.

PMID- 28752173
TI  - Improved i-motif thermal stability by insertion of anthraquinone monomers.
AB  - In order to gain insight into how to improve thermal stability of i-motifs when
      used in the context of biomedical and nanotechnological applications, novel
      anthraquinone-modified i-motifs were synthesized by insertion of 1,8-, 1,4-, 1,5-
      and 2,6-disubstituted anthraquinone monomers into the TAA loops of a 22mer
      cytosine-rich human telomeric DNA sequence. The influence of the four
      anthraquinone linkers on the i-motif thermal stability was investigated at 295 nm
      and pH 5.5. Anthraquinone monomers modulate the i-motif stability in a position
      depending manner and the modulation also depends on the substitution pattern of
      the anthraquinone. The insertion of anthraquinone was found to stabilize the i
      motif structure when replacing any one of the positions of the central TAA loop
      and the thermal stabilities were typically higher than those previously found for
      i-motifs containing pyrene-modified uracilyl unlocked nucleic acid monomers or
      twisted intercalating nucleic acid. The 2,6-disubstituted anthraquinone linker
      replacing T10 enabled a significant increase of i-motif thermal melting by 8.2 
      degrees C. A substantial increase of 5.0  degrees C in i-motif thermal melting
      was recorded when both A6 and T16 were modified with a double replacement by the
      2,6-isomer into the TAA loops in the outer regions. The largest destabilization
      is observed for the 1,5-disubstituted anthraquinone linker upon the replacement
      of A18. CD curves of anthraquinone-modified variants imply no structural changes
      in all cases under potassium buffer conditions compared with those of the native
      i-motif. Molecular modeling studies explained the increased thermal stabilities
      of anthraquinone-modified i-motifs.

PMID- 28752174
TI  - Transferrin-coated magnetic upconversion nanoparticles for efficient photodynamic
      therapy with near-infrared irradiation and luminescence bioimaging.
AB  - In the present study, we devised a green-synthesis route to NaYF4:Gd3+,Yb3+,Er3+
      upconversion nanoparticles (UCNPs) by using eco-friendly paraffin liquid, instead
      of 1-octadecene, as a high boiling non-coordinating solvent. A multifunctional
      nanoplatform was then developed by coating UCNPs with biocompatible transferrin
      (TRF) for magnetically-assisted and near-infrared light induced photodynamic
      therapy and bioimaging. Protoporphyrin IX (PpIX), a clinically approved
      photodynamic therapy agent, was loaded into the shell layer of the TRF-coated
      UCNPs (UCNP@TRF nanoparticles), which can be efficiently taken up by cancer cells
      for photodynamic therapy. Upon near-infrared light irradiation, the UCNP@TRF-PpIX
      nanoparticles could not only kill the cancer cells via photodynamic therapy but
      also serve as imaging probes. We also demonstrated that an external magnetic
      field could be used to increase the uptake of UCNP@TRF-PpIX nanoparticles by MDA
      MB-231 and HeLa cancer cells, and hence result in an enhanced photodynamic
      therapy efficiency. This work demonstrates the innovative design and development
      of high-performance multifunctional PDT agents.

PMID- 28752175
TI  - Proof of principle of a three-input AND-INHIBIT-OR combinatorial logic gate
      array.
AB  - A designed molecule fluoresces according to a combinatorial logic circuit
      equivalent to wiring together three-input AND, three-input INHIBIT and two-input
      OR logic gates.

PMID- 28752176
TI  - Enhancement of the dielectric response in polymer nanocomposites with low
      dielectric constant fillers.
AB  - In order to increase the dielectric constants of polymer-based dielectrics,
      composite approaches, in which inorganic fillers with much higher dielectric
      constants are added to the polar polymer matrix, have been investigated. However,
      high dielectric constant fillers cause high local electric fields in the polymer,
      resulting in a large reduction of the electric breakdown strength. We show that a
      significant increase in the dielectric constant can be achieved in polyetherimide
      nanocomposites with nanofillers whose dielectric constant can be similar to that
      of the matrix. The presence of nanofillers reduces the constraints on the dipole
      response to the applied electric field, thus enhancing the dielectric constant.
      Our results demonstrate that through nanostructure engineering, the dielectric
      constant of nanocomposites can be enhanced markedly without using high dielectric
      constant nanofillers.

PMID- 28752177
TI  - "On water" catalytic enantioselective sulfenylation of deconjugated
      butyrolactams.
AB  - The first catalytic enantioselective alpha-sulfenylation of deconjugated
      butyrolactams has been developed using dimeric cinchona alkaloids as catalysts in
      a water-enriched reaction medium. Highly substituted and densely functionalized
      gamma-lactams, bearing a quaternary stereogenic center, are produced with up to
      99.5 : 0.5 er. The applicability of the same catalyst system for the
      enantioselective alpha-selenylation and formal vinylogous gamma-hydroxylation of
      deconjugated butyrolactam has also been described.

PMID- 28752178
TI  - Inhibitory effect of JAK inhibitor on mechanical stress-induced protease
      expression by human articular chondrocytes.
AB  - OBJECTIVE: To investigate whether janus kinase (JAK) inhibitor exhibits a chondro
      protective effect against mechanical stress-induced expression of a disintegrin
      and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix
      metalloproteinase (MMPs) in human chondrocytes. MATERIALS AND METHODS: Normal
      human articular chondrocytes were seeded onto stretch chambers and incubated with
      or without tofacitinib (1000 nM) for 12 h before mechanical stimulation or
      cytokine stimulation. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 10%
      elongation, 30 min) was applied and the gene expression levels of type II
      collagen alpha1 chain (COL2A1), aggrecan (ACAN), ADAMTS4, ADAMTS5, MMP13, and
      runt-related transcription factor 2 (RUNX-2) were examined by real-time
      polymerase chain reaction. Nuclear translocation of RUNX-2 and nuclear factor
      kappaB (NF-kappaB) was examined by immunocytochemistry, and phosphorylation of
      mitogen-activated protein kinase (MAPK) and signaling transducer and activator of
      transcription (STAT) 3 was examined by western blotting. The concentration of
      interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in the supernatant
      was examined by enzyme-linked immunosorbent assay. RESULTS: COL2A1 and ACAN gene
      expression levels were decreased by CTS, but these catabolic effects were
      canceled by tofacitinib. Tofacitinib significantly down-regulated CTS-induced
      expression of ADAMTS4, ADAMTS5, MMP13, and RUNX2, and the release of IL-6 in
      supernatant by chondrocytes. Tofacitinib also reduced CTS-induced nuclear
      translocation of RUNX-2 and NF-kappaB, and phosphorylation of MAPK and STAT3.
      CONCLUSION: Tofacitinib suppressed mechanical stress-induced expression of
      ADAMTS4, ADAMTS5, and MMP13 by human chondrocytes through inhibition of the
      JAK/STAT and MAPK cascades.

PMID- 28752179
TI  - [Clinical autopsies in Switzerland : A status report].
AB  - BACKGROUND: The number of autopsies has been steadily declining worldwide over
      the past decades. The reasons for this are diverse. Legislation regarding
      opposition and consent rules does not appear to have had a significant impact on
      the autopsy rates. Above all, structural causes and the attitude of the medical
      profession are the reasons for this decline. The main argument for a high autopsy
      rate is the identification of diagnostic errors; however, diagnostic
      discrepancies are relatively independent of the rate of autopsies performed. At
      the University Hospital (UniversitatsSpital) Zurich it could be shown in a study
      that from 1972-2002 the frequency of relevant diagnostic discrepancies (classes I
      and II) decreased from 30% to 7%. OBJECTIVE: The aim of this article is to
      present the necessity of a stable autopsy rate and to examine the situation of
      the autopsy in Switzerland. MATERIAL AND METHODS: For this purpose, the
      importance of autopsies in the fields of quality assurance of medical
      diagnostics, cancer statistics, medical research as well as further education of
      doctors in Switzerland is shown. Efforts are being made by the pathologists to
      counteract the declining autopsy rates. RESULTS AND DISCUSSION: Declining autopsy
      numbers have a significant influence on cancer statistics. The rate of newly
      discovered tumors in autopsies in Switzerland decreased from 42% in 1980 to 17%
      in 2010. Pediatric autopsies are an important tool for quality assurance of
      medical diagnostics in neonatology and pediatrics in Switzerland, but the rate of
      autopsies carried out is also declining. Postmortem magnetic resonance imaging
      (MRI) examinations (virtopsy) could increase the acceptance of the parents for an
      autopsy in the future. Autopsies make an important contribution in research and
      in documentation of therapy-associated side effects and they are an important
      component of further education of the upcoming medical generations.

PMID- 28752180
TI  - The Difference of Photosynthetic Responses to the Cadmium Stress Between a Wild
      Soybean (Glycine soja Sieb. et Zucc.) and a Cultivated Soybean.
AB  - The effects of Cd on a halophyte of Doingying wild soybean (DY-03262) were
      studied by comparing it with a cultivated soybean (SN-11) via investigating
      photosynthetic activity, chlorophyll fluorescence and Cd concentrations in leaves
      after treatment with different concentrations of Cd (0, 50, and 100 MUM) for 10
      days. There were no significant differences in photosynthetic rate (PN), actual
      photochemical efficiency of PSII (PhiPSII), stomatal conductance (gs), and
      photochemical quenching (qP) between the both soybean species without Cd
      treatment, but they decreased greater in DY-03262 than that in SN-11 leaves after
      Cd treatment. The study demonstrated that the decrease in PN were significantly
      correlated with Cd concentrations in the leaves of both soybeans species. The
      greater decreases in photosynthetic activity of the DY-03262 were due to the
      higher Cd concentrations in its leaves.

PMID- 28752181
TI  - Asymmetric response of root-associated fungal communities of an arbuscular
      mycorrhizal grass and an ectomycorrhizal tree to their coexistence in primary
      succession.
AB  - The arbuscular mycorrhizal (AM) grass Calamagrostis epigejos and predominantly
      ectomycorrhizal (EcM) tree Salix caprea co-occur at post-mining sites
      spontaneously colonized by vegetation. During succession, AM herbaceous
      vegetation is replaced by predominantly EcM woody species. To better understand
      the interaction of AM and EcM plants during vegetation transition, we studied the
      reciprocal effects of these species' coexistence on their root-associated fungi
      (RAF). We collected root and soil samples from three different microenvironments:
      stand of C. epigejos, under S. caprea canopy, and contact zone where roots of the
      two species interacted. RAF communities and mycorrhizal colonization were
      determined in sampled roots, and the soil was tested for EcM and AM inoculation
      potentials. Although the microenvironment significantly affected composition of
      the RAF communities in both plant species, the effect was greater in the case of
      C. epigejos RAF communities than in that of S. caprea RAF communities. The
      presence of S. caprea also significantly decreased AM fungal abundance in soil as
      well as AM colonization and richness of AM fungi in C. epigejos roots. Changes
      observed in the abundance and community composition of AM fungi might constitute
      an important factor in transition from AM-dominated to EcM-dominated vegetation
      during succession.

PMID- 28752182
TI  - The challenging surgical treatment of closed distal humerus fractures in elderly
      and octogenarian patients: radiographic and functional outcomes with a minimum
      follow-up of 24 months.
AB  - INTRODUCTION: The main purpose of this retrospective, non-randomized, case series
      study was to evaluate the clinical and radiographic outcomes of distal humerus
      fractures (DHFs) in a consecutive series of elderly patients operatively treated
      by two surgeons, and second, to identify proper indications for two elderly age
      ranges and two fracture pattern groups. MATERIALS AND METHODS: From January 2009
      to June 2014, 51 patients (pts) underwent open reduction and internal fixation
      (ORIF) using the locking compression plate (LCP) distal humerus plate (DHP)
      system at our institution. Medical records and radiographs were retrospectively
      assessed. Patients were divided into 3 groups according to gender, age (pts <85
      years, pts >=85 years) and AO classification (13-B1-B2-C1-C2 or 13-C3). All
      subjects completed MEPS, Quick-DASH and SF-36 PCS/MCS scores at final follow-up,
      and statistical analysis was performed. RESULTS: 36 patients (20 women, 16 men),
      mean age 80.3 years, with AO type 13-B and 13-C DHFs were included with a mean
      follow-up of 56 months (range 24-92). The most common mechanism of trauma was a
      fall from ground level (55.6%). The mean MEPS was 78.9 points, Quick-DASH 28.4,
      SF-36 PCS 48.3 and MCS 48.9. There was statistically significant evidence that
      having a 13-C3 fracture leads to worse results in MEPS, Quick-DASH and SF-36. The
      female gender correlates with worse results in SF-36. The patients >=85 years had
      a worse prognosis according to Quick-DASH and SF-36, while the AO 13-C3 pattern
      obtained the worst ROM outcomes versus AO 13 B1-B2-C1-C2 (normal ROM 0 degrees 
      140 degrees ): mean ROM 24 degrees -114 degrees  vs 10 degrees -130 degrees ,
      mean flexion deficit 26 degrees  vs 10 degrees , mean extension deficit 24
      degrees  vs 10 degrees , respectively). Complications were presents in 36.1% of
      patients, overall belonging to the AO type 13-C fracture pattern and to the group
      >=85 years. CONCLUSION: These study data seem to confirm our hypothesis that
      plate fixation for DHFs guarantees adequate fracture osteosynthesis and
      satisfactory functional outcomes at medium to long-term follow-up, not only in
      elderly patients, but also in octogenarian osteoporotic patients (>=85 years)
      with 13-C1 and 13-C2 fracture patterns, while an alternative solution should be
      considered for type C3 fractures, even in a primary trauma setting.

PMID- 28752183
TI  - [Erratum to: Residual neuromuscular blockade].

PMID- 28752184
TI  - [Hans F. E. Killian and Rudolf Frey-two pioneers of German anesthesia].

PMID- 28752185
TI  - The subchondral bone healing after fixation of an osteochondral talar defect is
      superior in comparison with microfracture.
AB  - PURPOSE: Arthroscopic bone marrow stimulation (BMS) has been considered the
      primary surgical treatment for osteochondral defects (OCDs) of the talus.
      However, fixation has been considered as a good alternative. Recently, a new
      arthroscopic fixation technique was described: the lift, drill, fill and fix
      procedure (LDFF). The purpose of this study was to evaluate the clinical and
      radiological results between arthroscopic LDFF and arthroscopic BMS in primary
      fixable talar OCDs at 1-year follow-up. METHODS: In a prospective comparative
      study, 14 patients were treated with arthroscopic BMS and 14 patients with
      arthroscopic LDFF. Pre- and postoperative clinical assessment included the
      American Orthopaedic Foot and Ankle Society (AOFAS) score and the numeric rating
      scales (NRSs) of pain at rest and running. Additionally, the level of the
      subchondral plate (flush or depressed) was analysed on the 1 year postoperative
      computed tomography scans. RESULTS: No significant differences in the AOFAS and
      NRS pain at rest and running were found between both groups at 1-year follow-up.
      After LDFF the level of the subchondral bone plate was flush in 10 patients and
      after BMS in three patients (p = 0.02). CONCLUSION: No clinical differences were
      found between arthroscopic LDFF and arthroscopic BMS in the treatment of talar
      OCDs at 1-year follow-up. However, the subchondral bone plate restores
      significantly superior after arthroscopic LDFF compared to arthroscopic BMS. It
      may therefore give less progression of ankle osteoarthritis in the future with a
      thus potential better long-term outcome. LEVEL OF EVIDENCE: III.

PMID- 28752186
TI  - Low-impact sports activities are feasible after meniscus transplantation: a
      systematic review.
AB  - PURPOSE: To determine sports activities achieved after meniscus transplantation
      and if associations exist between sports activity levels and transplant failure
      or progression of tibiofemoral osteoarthritis (OA). METHODS: A systematic search
      was performed using PubMed and Cochrane online databases. Inclusionary criteria
      were English language, clinical trials published from 1996 through May 2017,
      minimum 2 years of follow-up, and sports activity data reported. RESULTS: Twenty
      eight studies were included in which 1521 menisci were implanted into 1497
      patients. The mean age was 34.3 +/- 6.7 years, and the mean follow-up was 5.0 +/-
      3.7 years. Details on sports activities were provided in 7 studies (285 patients)
      that reported 70-92% of patients returned to a wide variety of sports activities.
      Mean Tegner activity scores were reported in 24 investigations. The mean score
      was <5 in 58% of these studies, indicating many patients were participating in
      light recreational activities. There was no association between mean Tegner
      scores and transplant failure rates. A moderate correlation was found between
      failure rates and mean follow-up time (R = 0.63). The effect of sports activity
      levels on progression of tibiofemoral OA could not be determined because of
      limited data. Only two studies determined whether symptoms occurred during sports
      activities; these reported 1/38 (3%) and 5/69 (7%) patients had knee-related
      problems. CONCLUSIONS: It appeared that the majority of individuals returned to
      low-impact athletic activities after meniscus transplantation. The short-term
      follow-up did not allow for an analysis on the effect of return to high-impact
      activities on transplant failure rates or progression of OA. LEVEL OF EVIDENCE:
      IV.

PMID- 28752187
TI  - Systematic review and network meta-analysis comparing palbociclib with
      chemotherapy agents for the treatment of postmenopausal women with HR-positive
      and HER2-negative advanced/metastatic breast cancer.
AB  - PURPOSE: To compare palbociclib + letrozole and palbociclib + fulvestrant with
      chemotherapy agents in postmenopausal women with hormone receptor-positive
      (HR+)/human epidermal growth factor receptor 2-negative (HER2-)
      advanced/metastatic breast cancer (ABC/MBC) who had no prior systemic treatment
      for advanced disease (first line) or whose disease progressed after prior
      endocrine therapy or chemotherapy (second line). METHODS: A systematic search
      identified randomized controlled trials (RCTs) published from January 2000 to
      January 2016 that compared endocrine-based therapies, chemotherapy agents, and/or
      chemotherapy agents + biological therapies in the first- and second-line
      treatment of postmenopausal women with HR+/HER2- ABC/MBC. The main outcome of
      interest was progression-free survival (PFS)/time to progression (TTP). Bayesian
      network meta-analyses (NMAs) and pairwise meta-analyses were conducted.
      Heterogeneity and inconsistency were assessed. RESULTS: Sixty RCTs met
      eligibility criteria and were stratified by line of therapy. In the first line,
      palbociclib + letrozole showed statistically significant improvements in PFS/TTP
      versus capecitabine [intermittent: HR 0.28 (95% CrI 0.11-0.72)] and mitoxantrone
      [HR 0.28 (0.13-0.61)], and trended toward improvements versus paclitaxel [HR 0.59
      (0.19-1.96)], docetaxel [HR 0.51 (0.14-2.03)] and other monotherapy or
      combination agents (HRs ranging from 0.24 to 0.99). In the second line,
      palbociclib + fulvestrant showed statistically significant improvements in
      PFS/TTP versus capecitabine [intermittent: HR 0.28 (0.13-0.65)], mitoxantrone [HR
      0.26 (0.12-0.53)], and pegylated liposomal doxorubicin [HR 0.19 (0.07-0.50)], and
      trended toward improvements versus paclitaxel [HR 0.48 (0.16-1.44)], docetaxel
      [HR 0.71 (0.24-2.13)] and other monotherapy or combination agents (HRs ranging
      from 0.23-0.89). NMA findings aligned with direct evidence and were robust to
      sensitivity analyses. CONCLUSIONS: Palbociclib + letrozole and palbociclib +
      fulvestrant demonstrate trends in incremental efficacy compared with chemotherapy
      agents for the first- and second-line treatment of HR +/HER2- ABC/MBC.

PMID- 28752188
TI  - Association between survival time with metastatic breast cancer and aggressive
      end-of-life care.
AB  - PURPOSE: For women with stage IV breast cancer (BC), the association between
      survival time (ST) and use of aggressive end-of-life (EOL) care is unknown.
      METHODS: We used the SEER-Medicare database to identify women with stage IV BC
      diagnosed 2002-2011 who died by 12/31/2012. Aggressive EOL care was defined as
      receipt in the last month of life: >1 ED visit, >1 hospitalization, ICU
      admission, life-extending procedures, hospice admission within 3 days of death,
      IV chemotherapy within 14 days of death, and/or >=10 unique physician encounters
      in the last 6 months of life. Receipt of aggressive EOL care and hospice in the
      last month of life were determined using claims, and multivariable analysis was
      used to identify factors associated with receipt. Costs of care were also
      evaluated. RESULTS: We identified 4521 eligible patients. Of these, 2748 (60.8%)
      received aggressive EOL care. Factors associated with aggressive EOL care were
      race (OR 1.45, 95% CI 1.19-1.81 for blacks compared to whites) and more frequent
      oncology office visits (OR 1.56, 95% CI 1.28-1.90). Patients who lived >12 months
      after diagnosis were less likely to receive aggressive EOL care (OR 0.44, 95% CI
      0.38-0.52), and more likely to utilize hospice (OR 1.43, 95% CI 1.21-1.69)
      compared to patients who lived <=6 months. Patients with a shorter ST had
      significantly higher costs of care per-month-alive compared to patients with
      longer ST. CONCLUSION: Patients with a shorter ST were more likely to receive
      aggressive EOL care and had higher costs of care compared to patients who lived
      longer.

PMID- 28752189
TI  - Impact of tissue-based genomic profiling on clinical decision making in the
      management of patients with metastatic breast cancer at academic centers.
AB  - BACKGROUND: Genomic profiling can identify targetable mutations; however, the
      impact of tissue-based genomic profiling on clinical decision making for patients
      with metastatic breast cancer has not been well characterized. METHODS: Patients
      with stage IV breast cancer who had undergone genomic profiling between 7/2013
      and 3/2015 were identified at three academic cancer centers. Genomic analysis was
      determined to have impacted clinical decision if (A) a patient was enrolled onto
      a genotype-matched clinical trial or (B) prescribed off-label an FDA-approved
      therapy targeting an identified mutation. The frequency of mutated genes was
      determined. RESULTS: A total of 117 patients with stage IV breast cancer were
      identified. Median age was 46 (25-75). Fifty-three patients (45%) had ER
      positive/HER2-negative disease, 50 (43%) had ER-negative/HER2-negative disease,
      and 14 (12%) had ER-any/HER2-positive disease. Median number of previous
      therapies received prior to genomic profiling was 2 (range 0-15), and median
      follow-up after testing was obtained after 5.8 months (range 0-24.4 months).
      Commercial reports indicated that 85 (73%) patients had at least one mutation
      targetable by an FDA-approved medication, and 112 (96%) patients had at least one
      clinical trial available; however, clinical management was only affected in 11
      patients (9%). The most frequent mutations observed were those in TP53, FGF,
      PI3KCA, MYC, ZNF, FGFR, CCND, ARID1A, GATA3, and MAP; frequencies of these
      mutations varied by clinical subtype. CONCLUSIONS: Tumor genomic profiling
      affected clinical management in a minority of patients with metastatic breast
      cancer, thus these data do not support the routine use of genomic profiling
      outside of a clinical trial.

PMID- 28752190
TI  - Postlactational involution biomarkers plasminogen and phospho-STAT3 are linked
      with active age-related lobular involution.
AB  - PURPOSE: Breast terminal duct lobular units undergo two distinctive physiological
      processes of involution: age-related lobular involution (LI), which is gradual
      and associated with decreased breast cancer risk, and postlactational involution,
      which is relatively precipitous, occurs with weaning, and has been associated
      with potentiation of tumor aggressiveness in animal models. Here we assessed
      whether markers of postlactational involution are associated with ongoing LI in a
      retrospective tissue cohort. METHODS: We selected 57 women from the Mayo Clinic
      Benign Breast Disease Cohort who underwent multiple biopsies and who were average
      age 48 at initial biopsy. Women were classified as having progressive or non
      progressive LI between initial and subsequent biopsy. Serial tissue sections were
      immunostained for plasminogen, matrix metalloproteinase 9 (MMP-9), phospho-STAT3
      (pSTAT3), tenascin C, Ki67, CD44, cytokeratin 14 (CK14), cytokeratin 19 (CK19),
      and c-myc. All but Ki67 were digitally quantified. Associations between maximal
      marker expression per sample and progressive versus non-progressive LI were
      assessed using logistic regression and adjusted for potential confounders.
      RESULTS: While no biomarker showed statistically significant association with LI
      progression when evaluated individually, lower expression of pSTAT3 (OR 0.35, 95%
      CI 0.13-0.82, p = 0.01) and higher expression of plasminogen (OR 2.89, 95% CI
      1.14-8.81, p = 0.02) were associated with progressive LI in models simultaneously
      adjusted for all biomarkers. Sensitivity analyses indicated that the
      strengthening in association for pSTAT3 and plasminogen with progressive LI was
      due to collinearity between these two markers. CONCLUSIONS: This is the first
      study to identify biomarkers of active LI. Our findings that plasminogen and
      pSTAT3 are significantly associated with LI suggest that they may represent
      signaling nodes or biomarkers of pathways common to the processes of
      postlactational involution and LI.

PMID- 28752191
TI  - Breast cancer family history leads to early breast cancer detection and optimal
      management.
AB  - PURPOSE: We investigated whether the relationship between family history (FH) of
      breast cancer and survival of women with breast cancer is related to the quality
      of care received, once adjusted for other prognostic variables using data from
      the Geneva population-based cancer registry and quality of care indicators
      defined by the European Society of breast cancer specialists (EUSOMA). METHODS:
      We included non-metastatic malignant breast tumor patients who had their surgery
      between 2001 and 2010. We assessed the association between FH and patient and
      tumor characteristics on one hand, and each quality of care indicator and an
      overall score of quality of care, on the other hand, through logistic regression.
      We assessed the impact of FH and the quality of care-score on 5-year survival
      with Cox regression adjusting for patient and tumor characteristics. RESULTS:
      2,672 patients were included in the study. Women with a positive FH were younger,
      more likely from Switzerland, screen detected, had positive estrogen and
      progesterone receptor status, and had smaller and ductal tumors. A positive FH
      was also associated with better management for several quality indicators. Women
      with a positive FH had a better crude survival (Hazard Ratio 0.61, p = 0.006).
      This association was not substantially affected when adjusting for quality of
      care. However, the effect of FH did not persist when also adjusting for patient
      and tumor characteristics. CONCLUSIONS: A positive FH of breast cancer is
      associated with earlier breast cancer diagnosis, better tumor features, and
      higher quality of care. These factors explain the better survival observed among
      breast cancer women with a positive FH as compared to women without positive FH.

PMID- 28752192
TI  - Erratum to: Risk of breast, endometrial, colorectal, and renal cancers in
      postmenopausal women in association with a body shape index and other
      anthropometric measures.

PMID- 28752193
TI  - Readmissions after continuous flow left ventricular assist device implantation.
AB  - Continuous flow left ventricular assist device (CF-LVAD) therapy has improved the
      survival of patients with advanced heart failure. However, the readmission rate
      of CF-LVAD patients is still relatively high. A total of 90 patients who received
      CF-LVADs between April 2011 and March 2016 at our institute and were discharged
      home were analyzed retrospectively. They were followed up through March 2017.
      Clinical data, including frequency, length and etiology of readmission, were
      obtained from medical records. The mean observation period after initial
      discharge was 713 +/- 322 days. In total, 73 patients (81%) had 236 readmissions,
      214 unplanned and 22 planned. The overall and unplanned readmission rates were
      1.34 and 1.22 per patient-year, respectively. The rate of freedom from unplanned
      first readmission at 1 year after initial discharge was 39%. The median interval
      between the previous hospital discharge and first and second readmissions was 311
      and 213 days, respectively (log-rank test, p = 0.117). The rate of readmission
      after more than three readmissions was significantly higher than that of first or
      second readmission (log-rank test, p < 0.001). The most common etiology of
      readmission was driveline infection (DLI) (36%), followed by stroke (9%). The
      median length of hospital stay due to DLI was 23 days. The patients with repeated
      unplanned readmissions had significantly lower EuroQol 5 dimensions questionnaire
      utility score than those with no or just one readmission. Readmission was common
      in CF-LVAD patients, and the most common etiology of readmissions was DLI. The
      interval to the next readmission seemed shorter for patients with repeated
      readmissions.

PMID- 28752195
TI  - Processing Lexical and Speaker Information in Repetition and Semantic/Associative
      Priming.
AB  - The purpose of this study is to investigate the interaction between processing
      lexical and speaker-specific information in spoken word recognition. The specific
      question is whether repetition and semantic/associative priming is reduced when
      the prime and target are produced by different speakers. In Experiment 1, the
      prime and target were repeated (e.g., queen-queen) or unrelated (e.g., bell
      queen). In Experiment 2, the prime and target were semantically/associatively
      related (e.g., king-queen) or unrelated (e.g., bell-queen). In both experiments,
      the prime and target were either produced by the same male speaker or two
      different male speakers. Two interstimulus intervals between the prime and target
      were used to examine the time course of processing speaker information. The tasks
      for the participants included judging the lexical status of the target (lexical
      decision), followed by judging whether the prime and target were produced by the
      same speaker or different speakers (speaker discrimination). The results showed
      that both lexical decision and speaker discrimination were facilitated to a
      smaller extent when the prime and target were produced by different speakers,
      indicating reduced repetition priming by speaker variability. In contrast,
      semantic/associative priming was not affected by speaker variability. The ISI
      between the prime and target did not affect either type of priming. In
      conclusion, speaker variability affects accessing a word's form but not its
      meaning, suggesting that speaker-specific information is processed at a
      relatively shallow level.

PMID- 28752194
TI  - From engineering to editing the rat genome.
AB  - Since its domestication over 100 years ago, the laboratory rat has been the
      preferred experimental animal in many areas of biomedical research (Lindsey and
      Baker The laboratory rat. Academic, New York, pp 1-52, 2006). Its physiology,
      size, genetics, reproductive cycle, cognitive and behavioural characteristics
      have made it a particularly useful animal model for studying many human disorders
      and diseases. Indeed, through selective breeding programmes numerous strains have
      been derived that are now the mainstay of research on hypertension, obesity and
      neurobiology (Okamoto and Aoki Jpn Circ J 27:282-293, 1963; Zucker and Zucker J
      Hered 52(6):275-278, 1961). Despite this wealth of genetic and phenotypic
      diversity, the ability to manipulate and interrogate the genetic basis of
      existing phenotypes in rat strains and the methodology to generate new rat models
      has lagged significantly behind the advances made with its close cousin, the
      laboratory mouse. However, recent technical developments in stem cell biology and
      genetic engineering have again brought the rat to the forefront of biomedical
      studies and enabled researchers to exploit the increasingly accessible wealth of
      genome sequence information. In this review, we will describe how a breakthrough
      in understanding the molecular basis of self-renewal of the pluripotent founder
      cells of the mammalian embryo, embryonic stem (ES) cells, enabled the derivation
      of rat ES cells and their application in transgenesis. We will also describe the
      remarkable progress that has been made in the development of gene editing enzymes
      that enable the generation of transgenic rats directly through targeted genetic
      modifications in the genomes of zygotes. The simplicity, efficiency and cost
      effectiveness of the CRISPR/Cas gene editing system, in particular, mean that the
      ability to engineer the rat genome is no longer a limiting factor. The selection
      of suitable targets and gene modifications will now become a priority: a
      challenge where ES culture and gene editing technologies can play complementary
      roles in generating accurate bespoke rat models for studying biological processes
      and modelling human disease.

PMID- 28752196
TI  - Persistent Disadvantages or New Opportunities? The Role of Agency and Structural
      Constraints for Low-Achieving Adolescents' School-to-Work Transitions.
AB  - School leavers with low educational attainment face great difficulties in their
      school-to-work transitions. They are, however, quite heterogeneous in terms of
      their personal and social resources. These within-group differences may influence
      who shows initiative during the school-to-work transition period and thereby
      helps employers recognize their learning potential at labor market entry. Yet
      this recognition also depends on the ways employers select applicants, which may
      prevent them from discovering such within-group differences. We therefore
      investigate the interplay between agency and its constraints, that is, whether
      higher cognitive and noncognitive skills and more parental resources provide low
      achieving school leavers with new opportunities in the school-to-work transition
      period or whether their low school attainment causes the persistency of their
      disadvantages. We use panel data from the German National Educational Panel Study
      (NEPS), which started in grade 9. The NEPS also includes school leavers from
      special-needs schools. Our sample consists of 3417 low-achieving adolescents (42%
      female), defined as adolescents who leave school with no or only a lower
      secondary school-leaving certificate. Their average school-leaving age is 16 to
      17 years. Our key findings are that the transition period opens up new
      opportunities only for those low-achieving adolescents with better vocational
      orientation and higher career aspirations, leading them to make stronger
      application efforts. The success of youth's initiative varies considerably by
      school-leaving certificate and school type but not by competences, noncognitive
      characteristics, and parental background. Thus, the label of "having low
      qualifications" is a major obstacle in this transition period-especially for the
      least educated subgroup. Their poor school attainment strongly disadvantages them
      when accessing the required training to become economically independent and hence
      in their general transition to adulthood. Our results are also of interest
      internationally, because participation in firm-based training programs functions
      as the entry labor market in Germany. Thus, similar explanations may apply to low
      achieving adolescents' difficulties in finding a job.

PMID- 28752197
TI  - The effect of different torque wrenches on rotational stiffness in compressive
      femoral nails: a biomechanical study.
AB  - PURPOSE: Rotation instability and locking screws failure are common problems. We
      aimed to determine optimal torque wrench offering maximum rotational stiffness
      without locking screw failure. METHODS: We used 10 conventional compression
      nails, 10 novel compression nails and 10 interlocking nails with 30 composite
      femurs. We examined rotation stiffness and fracture site compression value by
      load cell with 3, 6 and 8 Nm torque wrenches using torsion apparatus with a
      maximum torque moment of 5 Nm in both directions. Rotational stiffness of
      composite femur-nail constructs was calculated. RESULTS: Rotational stiffness of
      composite femur-compression nail constructs compressed by 6 Nm torque wrench was
      3.27 +/- 1.81 Nm/angle (fracture site compression: 1588 N) and 60% more than that
      compressed with 3 Nm torque wrench (advised previously) with 2.04 +/- 0.81
      Nm/angle (inter fragmentary compression: 818 N) (P = 0.000). Rotational stiffness
      of composite-femur-compression nail constructs compressed by 3 Nm torque wrench
      was 2.04 +/- 0.81 Nm/angle (fracture site compression: 818 N) and 277% more than
      that of interlocking nail with 0.54 +/- 0.08 Nm/angle (fracture site compression:
      0 N) (P = 0.000). CONCLUSION: Rotational stiffness and fracture site compression
      value produced by 3 Nm torque wrench was not satisfactory. To obtain maximum
      rotational stiffness and fracture site compression value without locking screw
      failure, 6 Nm torque wrench in compression nails and 8 Nm torque wrench in novel
      compression nails should be used.

PMID- 28752198
TI  - Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort
      study and meta-analysis of published observational cohort studies.
AB  - The renin-angiotensin system (RAS) represents an important target of
      antihypertensive medications. Angiotensin-converting enzyme inhibitors (ACEI) and
      angiotensin II receptor blockers (ARB), which are widely-used RAS inhibiting
      drugs, have been suggested to have beneficial effects on bone tissue. We aimed to
      assess the associations of use of ACEIs and/or ARBs with the risk of fractures
      using a population-based prospective cohort and a meta-analysis of published
      prospective cohort studies. Information on antihypertensive medication use
      (including both ACEIs and ARBs) were assessed in 1743 men and women of the Kuopio
      Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) [95%
      confidence intervals (CI)] of ACEIs or ARBs use with incident fractures were
      calculated. A total of 203 composite (hip, humeral, and wrist) fractures occurred
      during a median follow-up of 14.8 years. In multivariate adjusted analysis, the
      HR for composite fractures comparing users of ACEIs or ARBs with non-users was
      1.00 (0.59-1.69). The corresponding adjusted HR for hip fractures comparing users
      versus non-users of ACEIs or ARBs was 0.89 (0.32-2.47). Including the current
      study, a total of 11 observational cohort studies involving 3526,319 participants
      and >323,355 fractures were included in a meta-analysis. Comparing ACEI users
      with non-users and ARB users with non-users, the HRs for composite fractures were
      1.09 (0.89-1.33) and 0.87 (0.76-1.01) respectively. The corresponding HRs for hip
      fractures were 0.91 (0.86-0.95) and 0.80 (0.75-0.85) respectively. Use of RAS
      inhibitors was not associated with long-term risk of composite fractures in both
      primary and pooled analyses. Pooled evidence however suggests a beneficial effect
      of RAS blockers on hip fracture risk.

PMID- 28752199
TI  - Thymus vulgaris L. and thymol assist murine macrophages (RAW 264.7) in the
      control of in vitro infections by Staphylococcus aureus, Pseudomonas aeruginosa,
      and Candida albicans.
AB  - : Microorganisms are capable to combat defense cells by means of strategies that
      contribute to their stabilization and proliferation in invaded tissues.
      Frequently antimicrobial-resistant strains appear; therefore, alternative methods
      to control them must be investigated, for example, the use of plant products. The
      capacity of the thyme extract (Thymus vulgaris L.) and phytocompound thymol in
      the control of in vitro infections by Staphylococcus aureus, Pseudomonas
      aeruginosa, and Candida albicans in murine macrophages (RAW 264.7) was evaluated.
      Minimal inhibitory concentrations (MIC) of the plant products were used. The
      effect of these MIC were analyzed in the assays of phagocytosis and
      immunoregulation by analysis of the production of cytokines (IL-1beta, TNF-alpha,
      and IL-10) and nitric oxide (NO). The plant products effectively assisted the
      macrophages in the phagocytosis of microorganisms, presenting significant
      reductions of S. aureus and P. aeruginosa. The macrophages also regulated the
      production of inflammatory mediators in the infections by S. aureus, P.
      aeruginosa, and C. albicans. In addition, thyme provided a satisfactory effect in
      response to the bacterial infections, regarding generation of NO. Thus, the
      effectiveness of the thyme and thymol to control in vitro infections by S.
      aureus, P. aeruginosa, and C. albicans was observed. HIGHLIGHTS: Phagocytosis of
      S. aureus by RAW 264.7 was enhanced with thymol Thyme enhanced the phagocytosis
      of P. aeruginosa by RAW 264.7 Plant products provided immunoregulation of
      inflammatory cytokines Production of nitric oxide was improved with the
      treatments in bacterial infections.

PMID- 28752200
TI  - Retrospective analysis of 769 cases of sudden cardiac death from 2006 to 2015: a
      forensic experience in China.
AB  - Sudden cardiac death (SCD) is a major health challenge. The records of 769
      autopsy cases of SCD examined at Tongji Medicolegal Expertise Center from January
      2006 to December 2015 were retrospectively reviewed. The mean age of the cases
      was 46 years, excluding 27 victims in whom the exact age could not be confirmed.
      The highest incidence of SCD occurred among the 40- to 60-year-old group (45.0%).
      Male preponderance was observed in SCD cases (male: female ratio: 5.0:1), and
      this preponderance was even higher (8.0:1) in the 10- to 20-year-old and 60- to
      70-year-old groups. Death predominantly occurred in hospitals (37.4%) and
      outdoors (32.5%). The incidence of SCD did not differ significantly between the
      seasons. Coronary atherosclerotic disease (CAD) was the main cause of SCD
      (67.9%), followed by unexplained SCD (6.1%), myocarditis (5.7%), cardiomyopathy
      (4.7%), rupture of aortic dissection (3.9%), and cardiac conduction system
      disease (3.9%). In terms of the CAD cases, the mean age was 52.0 years and
      coronary artery stenosis exceeding 75% accounted for 73.6% of cases. The left
      anterior descending branch was involved with atherosclerosis in 92.0% of cases.
      In conclusion, detailed autopsy and forensic pathology examination is key to
      diagnosing SCD. Making an early diagnosis and performing early intervention of
      CAD may reduce the mortality of SCD. Additionally, the use of molecular genetic
      tests plus forensic pathology diagnosis will help further determine the
      underlying cause of death in individuals with SCD.

PMID- 28752202
TI  - Pediatric central nervous system hemangioblastomas: different from adult forms? A
      retrospective series of 25 cases.
AB  - BACKGROUND: Pediatric hemangioblastomas are rare, and the clinical features,
      timing of surgical intervention, optimal treatment, and clinical outcomes are
      still unclear. METHODS: We performed a retrospective study of all patients with
      CNS hemangioblastomas who were treated at West China Hospital from January 2003
      to March 2015. Patients under the age of 16 years were included in the study. The
      medical records of these patients were reviewed and statistically analyzed.
      RESULTS: Twenty-five children (15 females and ten males, [mean age 12.6 +/- 4.7
      years, range 1-16 years]) presented with hemangioblastomas. Tumors were detected
      in the cerebellum, brainstem, and spinal cord in 40, 28, and 32% of patients,
      respectively. Sixteen children (64%) had VHL syndrome. The most frequent symptoms
      were those related to increased intracranial pressure. The mean duration of
      symptoms was 1.5 +/- 2.1 months. Preoperative hydrocephalus was noted in 11
      children (44%). Gross total resection was achieved in all children. Clinical
      symptoms improved in 19 children (76%), unchanged in four children (16%), and
      aggravated in two children (8%), respectively. The mean follow-up was 44.5 +/-
      32.3 months. Five patients (20%) experienced disease progression. Using
      univariate analysis, both tumor-associated cysts (P = 0.027) and VHL disease (P =
      0.032) were significantly related to postoperative outcomes. CONCLUSIONS:
      Pediatric hemangioblastomas have many different clinical features compared with
      adult cases. A high degree of suspicion for VHL disease should be raised in
      pediatric hemangioblastomas. Despite many challenges involved, surgical outcomes
      for pediatric hemangioblastomas are favorable. Lifelong follow-up is mandatory to
      detect the disease progression.

PMID- 28752201
TI  - The mitochondrial epitranscriptome: the roles of RNA modifications in
      mitochondrial translation and human disease.
AB  - Mitochondrial protein synthesis is essential for the production of components of
      the oxidative phosphorylation system. RNA modifications in the mammalian
      mitochondrial translation apparatus play key roles in facilitating mitochondrial
      gene expression as they enable decoding of the non-conventional genetic code by a
      minimal set of tRNAs, and efficient and accurate protein synthesis by the
      mitoribosome. Intriguingly, recent transcriptome-wide analyses have also revealed
      modifications in mitochondrial mRNAs, suggesting that the concept of dynamic
      regulation of gene expression by the modified RNAs (the "epitranscriptome")
      extends to mitochondria. Furthermore, it has emerged that defects in RNA
      modification, arising from either mt-DNA mutations or mutations in nuclear
      encoded mitochondrial modification enzymes, underlie multiple mitochondrial
      diseases. Concomitant advances in the identification of the mitochondrial RNA
      modification machinery and recent structural views of the mitochondrial
      translation apparatus now allow the molecular basis of such mitochondrial
      diseases to be understood on a mechanistic level.

PMID- 28752203
TI  - Treatment of atlanto-axial subluxation secondary to rheumatoid arthritis by short
      segment stabilization with polyaxial screws.
AB  - OBJECTIVE: The main aim of this study was to analyse the compex clinical and
      radiographic findings in a group of RA patients with atlanto-axial slip (AAS)
      treated with free-hand short C1 lateral mass and C2 trans-pedicular screw
      fixation. The surgical technique used and the pathology treated were the same in
      all patients, producing a very homogeneous cohort of patients This allowed the
      study and measurement of radiographic parameters and fusion process. METHODS:
      Twenty-nine patients (21 female, 8 male, mean age 54.9 years, duration of RA 17.3
      years) with AAS and without CS were treated by short C1/2 fixation. Mean follow
      up was 4.5 years. Pain intensity was monitored using VAS. Radiographic assessment
      consisted of lateral cervical radiographs in neutral and dynamic views, MR and CT
      of the cervical spine. The AADI, PADI, AAA, sub-axial cervical Cobb angle and
      canal-clivus angle (CCA) were measured pre-operatively and during the follow-up.
      RESULTS: Significant malposition was recorded in 4 (3.4%) out of 116 inserted
      screws. AADI, PADI, AAA and CCA values changed significantly after surgery and
      remained stable during follow-up. The Cobb C angle value showed no significant
      change after surgery. There was a significant decrease of the VAS after the
      surgery. Fusion or a stable situation was achieved in all patients at 2-year
      follow-up. Pannus regression was observed in the vast majority of patients; only
      in two cases was rheumatic tissue detected on MR at 2 years post-operatively.
      CONCLUSION: C1 lateral mass and C2 trans-pedicular fixation with polyaxial screws
      followed by an autograft between C1 and C2 lamina allowed, with an acceptable
      complication rate and favourable clinical results, adequate slip reposition,
      introduction of optimal sagittal alignment in terms of the final AAA with no
      radiographic consequences for the sub-axial cervical spine and assurance of long
      term stability.

PMID- 28752204
TI  - Topical application of palmitoyl-RGD reduces human facial wrinkle formation in
      Korean women.
AB  - Maintaining a youthful appearance is a common desire among the aging population.
      Loss of elasticity and dermal density constitutes major causes of wrinkle
      formation during skin aging. In particular, periorbital wrinkles comprise the
      critical assessment point of skin aging. To address these issues, cosmetic
      industries have been making increasing efforts to develop efficient agents
      against wrinkle formation. Arg-Gly-Asp (RGD) is a tripeptide sequence used for
      surface coating because of its integrin-binding property. However, its
      pharmacological properties on skin have not yet been studied. Here, we synthesize
      the novel palmitoyl-Arg-Gly-Asp (Palm-RGD) and investigate its effects on
      periorbital wrinkle formation by clinical and in vitro studies. We observed that
      Palm-RGD cream application for 12 weeks decreased global photodamage and skin
      roughness (R1, R2, R3, and Ra) scores without causing skin irritation. In
      addition, topical application of Palm-RGD cream time-dependently increased skin
      elasticity and dermal density. An in vitro study using human dermal fibroblasts
      (HDFs) demonstrated increased type I procollagen production by Palm-RGD
      treatment. Furthermore, Palm-RGD suppressed MMP-1 expression in HDFs. Our results
      demonstrate that Palm-RGD has protective effects against wrinkle formation,
      likely through the activation of collagen expression and the protection against
      collagen degradation. Therefore, Palm-RGD could be used as a potential agent for
      the prevention of wrinkle formation consequent to aging.

PMID- 28752205
TI  - Post-operative radiological predictors of satisfying outcomes occurring after
      intra-articular calcaneal fractures: a three dimensional CT quantitative
      evaluation.
AB  - PURPOSE: No functional outcome related to 3-D CT evaluations for calcaneal
      fractures has been presented. The aims of this study are to analyze the post
      operative morphological parameters of calcaneal fractures in 3-D space and to
      correlate the 3-D morphological parameters with functional outcomes. METHODS:
      Between 2009 and 2015, 156 patients operatively treated for displaced calcaneal
      fractures were retrospectively reviewed with an average follow-up time of 32.4
      months. Bohler's angle, Gissane's angle, the length of calcaneal axis, the height
      of posterior facet, the length of posterior facet, and the subtalar joint
      congruity were evaluated post-operatively in accordance with 3-D CT. Each
      parameter was quantified, and then its association with the clinical outcomes
      assessed by the AOFAS score and Short Form-36 questionnaire was evaluated.
      RESULTS: The restoration of the length of calcaneal axis, the height of posterior
      facet, and the length of posterior facet had no significant correlation with the
      clinical outcomes (P > 0.05). The restoration of Bohler's angle and Gissane's
      angle had significant correlation with the better AOFAS score (P < 0.001), while
      no correlation was found with the SF-36 physical component summary score (P >
      0.05). No significant association emerged between the clinical outcomes and
      reconstruction of the posterior facet congruity (P > 0.05). CONCLUSION: The
      predictable functional outcome is related to the reconstruction of post-operative
      morphological characteristics of the calcaneus as evaluated on 3-D CT, especially
      the Bohler's angle and Gissane's angle. Despite post-operative step-off of the
      posterior facet exiting, the clinical outcomes appear to be not related to the
      posterior facet congruity.

PMID- 28752206
TI  - Surgical treatment of pelvic sarcoma in children: outcomes for twenty six
      patients.
AB  - PURPOSE: Pelvic sarcoma is uncommon in children and challenging to treat. This
      study examined different surgical approaches to treat pelvic sarcoma with the aim
      of assessing the oncologic, and functional outcomes. METHODS: We retrospectively
      examined the medical records of patients younger than 21 years of age who
      underwent surgery for pelvic sarcoma at our institution from 1992 to 2010. The
      functional status of the patients was examined after a minimum follow-up of two
      years. RESULTS: Twenty-six patients were included in the analysis. Nineteen (73%)
      patients were male and seven (27%) were female. Mean age at presentation was 12.0
      +/- 3.9 years. Nineteen patients had Ewing sarcoma (73%), five had osteosarcoma
      (19%), one had chondrosarcoma (4%) and one had rhabdomyosarcoma (4%). Iliac wing
      resection with no reconstruction was done in three patients. Reconstruction with
      free fibular graft A-frame was performed in four patients, saddle endoproshtesis
      in five patients, iliac autoclave in one patient, and internal hemipelvectomy in
      nine patients. Hindquarter amputation was performed in five patients. Median
      follow-up was 4.6 years (range, 2.6-16 years). Nineteen patients were alive
      (73%); of those, 13 were known to be without disease, three were with disease and
      three did not have known tumor status. Six patients were reported deceased, three
      had osteosarcoma and three had Ewing sarcoma. Function was assessed in 17
      patients; 64% were asymptomatic and ambulatory and 36% were symptomatic and
      ambulatory. CONCLUSIONS: Salvage reconstruction for pelvic sarcoma can be
      performed through various procedures on the extent of necessary bony resection.
      Survival rate and functional outcomes were promising in the performed study.

PMID- 28752207
TI  - Conformational changes, from beta-strand to alpha-helix, of the fatty acid
      binding protein ReP1-NCXSQ in anionic lipid membranes: dependence with the
      vesicle curvature.
AB  - We studied the conformational changes of the fatty acid-binding protein ReP1
      NCXSQ in the interface of anionic lipid membranes. ReP1-NCXSQ is an acidic
      protein that regulates the activity of the Na+/Ca2+ exchanger in squid axon. The
      structure is a flattened barrel composed of two orthogonal beta-sheets delimiting
      an inner cavity and a domain of two alpha-helix segments arranged as a hairpin.
      FTIR and CD spectroscopy showed that the interactions with several anionic lipids
      in the form of small unilamellar vesicles (SUVs) induced an increase in the
      proportion of helix secondary structure. Lower amount or no increase in alpha
      helix was observed upon the interaction with anionic lipids in the form of large
      unilamellar vesicles (LUVs). The exception was 1,2-dimyristoyl-sn-glycero-3
      phosphoglycerol (DMPG) that was equally efficien to to induce the conformational
      change both in SUVs and in LUVs. In solution, the infrared spectra of ReP1-NCXSQ
      at temperatures above the unfolding displayed a band at 1617 cm-1 characteristic
      of aggregated strands. This band was not observed when the protein interacted
      with DMPG, indicating inhibition of aggregation in the interface. Similarly to
      the observed in L-BABP, another member of the fatty acid binding proteins, a
      conformational change in ReP1-NCXSQ was coupled to the gel to liquid-crystalline
      lipid phase transition.

PMID- 28752208
TI  - MicroRNAs in Atrial Fibrillation: from Expression Signatures to Functional
      Implications.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia and is
      associated with pronounced morbidity and mortality. Its prevalence, expected to
      further increase for the forthcoming years, and associated frequent
      hospitalizations turn AF into a major health problem. Structural and electrical
      atrial remodelling underlie the substrate for AF, but the exact mechanisms
      driving this remodelling remain incompletely understood. Recent studies have
      shown that microRNAs (miRNA), short non-coding RNAs that regulate gene
      expression, may be involved in the pathophysiology of AF. MiRNAs have been
      implicated in AF-induced ion channel remodelling and fibrosis. MiRNAs could
      therefore provide insight into AF pathophysiology or become novel targets for
      therapy with miRNA mimics or anti-miRNAs. Moreover, circulating miRNAs have been
      suggested as a new class of diagnostic and prognostic biomarkers of AF. However,
      the origin and function of miRNAs in tissue and plasma frequently remain unknown
      and studies investigating the role of miRNAs in AF vary in design and focus and
      even present contradicting results. Here, we provide a systematic review of the
      available clinical and functional studies investigating the tissue and plasma
      miRNAs in AF and will thereafter discuss the potential of miRNAs as biomarkers or
      novel therapeutic targets in AF.

PMID- 28752209
TI  - Plasma Lipidome Analysis by Liquid Chromatography-High Resolution Mass
      Spectrometry and Ion Mobility of Hypertriglyceridemic Patients on Extended
      Release Nicotinic Acid: a Pilot Study.
AB  - BACKGROUND: Plasma high triacylglycerols and low HDL-C concentration are
      associated with increased cardiovascular events. Extended-release nicotinic acid
      (ERN) was shown to reduce plasma triacylglycerols and total cholesterol but also
      to markedly increase high-density lipoprotein-cholesterol (HDL-C). No data on the
      effect of ERN on different species of triacylglycerol, cholesteryl ester, and
      phospholipids are available. In this study, we applied a nontargeted lipidomic
      approach to investigate the plasma and lipoproteins lipids profile of
      hypertriglyceridemic patients treated with ERN or a placebo in order to identify
      new lipids markers associated with this treatment. METHODS: Eight
      hypertriglyceridemic patients enrolled in a crossover randomized trial with ERN
      for 8 weeks and treated with 2 g/day of ERN or a placebo. Ultra-performance
      liquid chromatography (UPLC) coupled to high-resolution mass spectrometry (HRMS)
      was used in mass spectrometry energy mode (HRMSE) combined with ion mobility
      spectrometry to characterize the plasma and very low density lipoprotein (VLDL),
      low density lipoprotein (LDL) and high density lipoprotein (HDL) lipidome. The
      accuracy and precision of the method were validated on plasma samples. RESULTS:
      Compared to placebo, among 155 plasma lipids characterized using UPLC-ESI-HRMS, a
      multivariate analysis revealed a significant increase of lysophosphatidylcholine
      (LPC 20:5), a significant decrease of phosphatidylethanolamine (PE 16:0/22:3) and
      sphingomyelin (SM d18:1/22:0) and a decrease of triacylglycerol (TG
      16:0/16:1/18:2) after ERN treatment. Analysis of these lipids in lipoproteins
      showed an increase of LPC (20:5) in HDL, a decrease of PE (16:0/22:3) in HDL and
      LDL, of SM (d18:1/22:0) in VLDL and LDL and of TG (16:0/16:1/18:2) in VLDL.
      CONCLUSION: This lipidomic strategy characterized new specific lipid markers
      likely to be involved in the effect of ERN on cardiovascular risk opening a new
      strategy to analyze randomized controlled with this treatment. TRIAL
      REGISTRATION: NCT01216956.

PMID- 28752210
TI  - Helicobacter pylori infection and atherosclerosis: is there a causal
      relationship?
AB  - For many years, the coexistence of Helicobacter pylori (H. pylori) infection and
      atherosclerotic diseases in a disproportional number of patients has inspired the
      presumption that a causal relationship exists between the conditions. This
      presumption was evidenced by the simultaneously declining epidemics of duodenal
      ulcer and coronary artery diseases in the United States in the past 40 years, and
      was further evidenced by the detection of H. pylori and their DNA in
      atherosclerotic plaques. Suggested mechanisms underlying this possible causality
      include intensified inflammatory stress, dyslipidemia, abnormal glucose
      metabolism, arterial stiffness, increased blood pressure and malnutrition.
      However, a causal relationship was disproved by results from other studies, which
      indicated that common risk factors shared by H. pylori infection and
      atherosclerosis, such as aging, cigarette smoking, disadvantageous socioeconomic
      status and high salt intake, may predestine their coexistence. Understanding the
      nature of the relationship between H. pylori infection and atherosclerosis is of
      vital importance, because a causality may indicate a possible strategy for
      preventing and treating atherosclerosis by eradicating H. pylori infection in
      selected individuals. This review assessed current evidence for and against a
      causal relationship between H. pylori infection and atherosclerosis.

PMID- 28752211
TI  - Relationship between teat morphological traits and subclinical mastitis in
      Frieswal dairy cows.
AB  - The present study was aimed to investigate the relationship between selected
      morphological traits of teat and subclinical mastitis (SCM) in Frieswal crossbred
      dairy cows. A total of 1040 quarters from 261 lactating cows were evaluated for
      teat shape (bottle/fleshy/collapsed/conical/normal/pencil and short), teat-end
      shape (dished/flat/funnel/pocketed/pointed and rounded), teat orientation
      (aligned/misaligned) and teat position (front and rear; left-sided and right
      sided). Each udder quarter was screened with California Mastitis Test (CMT) for
      the purpose of defining quarter health status. Data were analysed using Chi
      square test and multivariable logistic regression procedure. An overall
      prevalence of SCM (CMT positive) at quarter level was 30.6%. Most of the teats
      had normal or cylindrical shapes (48%), dished teat-ends (40.7%), and aligned
      (central or squared) in orientation (65%). At bivariable level, significant
      association of SCM with teat shape, teat position, teat orientation, parity, and
      stage of lactation was observed (P < 0.05 to P < 0.001). Teat-end shapes showed
      some association with SCM (P = 0.07). Results of multivariable analysis showed
      that pencil-shaped teats were least associated with SCM (P < 0.05) as compared to
      other teat shapes. Prevalence of SCM was also higher in rear teats (P = 0.015),
      misaligned teats (P = 0.01), and cows in second or higher parities (P < 0.01) and
      late stage of lactation (P < 0.001). The results of the present study indicate
      that selected morphological traits of teat are associated with SCM in Frieswal
      crossbred cows; therefore, selection towards desirable morphological traits could
      help reduce mastitis in this breed.

PMID- 28752212
TI  - Factors affecting the livestock herd size among smallholder households in Zambia.
AB  - Structural changes in the economic and demographic landscapes in the developing
      countries create a host of opportunities for smallholder livestock producers to
      tap into the economic growth from which they have largely been excluded. However,
      small livestock herd sizes limit the opportunities available to farmers to
      commercialize and benefit from the growing demand for livestock and livestock
      products. Therefore, understanding what it takes to build and maintain the herd
      size is a critical step in addressing the problem of low market participation.
      The study used five cross-sectional nationally representative data sets to arrive
      at the following conclusions. While purchases are a primary source for the
      initial stock, births are the principal way of increasing the herd size.
      Livestock deaths as reflected by high mortality rates are the major outflow
      channel through which livestock leaves the herd, and reducing the mortality rates
      has a positive effect on the livestock population as evidenced within the cattle
      sub-sector. Thus, provision of adequate animal health services is key to
      addressing the high mortality rates which subsequently can lead to increased herd
      size. As births are the primary means of increasing the herd size, it is
      necessary to implement interventions that address the reproduction rates. The
      interventions include adequate feeding of livestock on high-quality feed and
      strategic feeding to address the dry season challenges. These interventions can
      facilitate the growth of the young livestock into mature breeding stock and thus
      increase the herd size.

PMID- 28752213
TI  - Changes of haemogram and serum biochemistry in neonatal piglet diarrhoea
      associated with porcine rotavirus type A.
AB  - Porcine rotavirus type A (RVA) is a major cause of neonatal piglet mortality in
      India. The effect of the disease on haemogram and serum biochemical profile is
      not well established in piglets. Accordingly, we assessed the haemogram and serum
      biochemical profile in the neonatal piglet diarrhoea with RVA infection (n = 17).
      The diagnosis of RVA was confirmed using RNA-polyacrylamide gel electrophoresis
      (RNA-PAGE), commercially available enzyme-linked immunosorbent assay (ELISA) kit
      and reverse transcription-polymerase chain reaction (RT-PCR). Non-infected
      healthy piglets (n = 6) served as control. The concentrations of total protein,
      albumin, alanine amino transaminase (ALT), aspartate amino transaminase (AST),
      blood urea nitrogen (BUN) and creatinine in serum were measured by
      spectrophotometric method. Haemogram was done in the blood using sodium
      ethylenediaminetetraacetic acid (Na2 EDTA) as anticoagulant. The mean values of
      total protein, albumin and globulin concentrations were significantly (P < 0.001)
      decreased and concentrations of ALT, AST, BUN and creatinine were significantly
      increased (P < 0.001) in the RVA-infected piglets. Haemogram showed marked
      haemoconcentration (P < 0.001), leukopenia (P < 0.01) and neutropenia (P < 0.01)
      in the presence of RVA infection than healthy piglets. The results indicated a
      possible extra-intestinal spread of RVA in piglets during neonatal diarrhoea. The
      finding might be helpful to clinicians and while treating such type of clinical
      cases, incorporation of organ protective drugs will be helpful for better
      response in the treatment schedule.

PMID- 28752214
TI  - Prevalence and risk factors associated with Theileria parva infection in cattle
      in three regions of Tanzania.
AB  - Ticks and tickborne diseases (TBDs) are serious constraints to cattle production
      in Tanzania and other tropical and subtropical countries. Among the TBDs, East
      Coast fever (ECF) is the most important as it causes significant economic losses
      to the cattle industry in Tanzania. However, control of ECF in Tanzania has
      continued to be a challenge due to inadequate epidemiological information. The
      main objective of this study was to determine the epidemiological situation of
      Theileria parva infections in cattle kept under pastoral and agro-pastoral
      farming systems in Mara, Singida, and Mbeya regions of Tanzania. Blood samples
      were collected from 648 cattle in the three regions. Genomic DNA was extracted
      and amplified in a polymerase chain reaction (PCR) using T. parva-specific
      primers targeting the 104-kD antigen (P104) gene. In addition, information was
      collected on the possible risk factors of T. parva infection (animal age, region,
      animal sex, tick burden, tick control method, and frequency of acaricide
      application). The prevalence of T. parva across the three regions was 14.2%.
      There was variation in prevalence among the three regions with Mara (21.8%)
      having a significantly higher (p = 0.001) prevalence than the other regions.
      Moreover, Mbeya exhibited relatively lower prevalence (7.4%) compared to the
      other regions. Factors found to be significantly associated with an animal being
      PCR positive for T. parva were region (p = 0.001) and tick burden (p = 0.003).
      Other factors were not found to be significant predictors of being PCR positive
      for T. parva. The present study showed high variation in tick burden and T. parva
      prevalence across the regions. Therefore, different strategic planning and cost
      effective control measures for ticks and T. parva infection should be implemented
      region by region in order to reduce losses caused by ticks and ECF in the study
      area.

PMID- 28752215
TI  - Epstein-Barr virus-positive ileal carcinomas associated with Crohn's disease.

PMID- 28752216
TI  - Improving mTICI2b reperfusion to mTICI2c/3 reperfusions: A retrospective
      observational study assessing technical feasibility, safety and clinical
      efficacy.
AB  - BACKGROUND: Recent studies suggested that modified Thrombolysis in Cerebral
      Infarction grade (mTICI) 3 reperfusions are associated with superior outcome to
      mTICI2b reperfusions, questioning if neurointerventionalists should generally
      strive to achieve mTICI3. METHODS: Retrospective analysis of successfully
      reperfused MCA occlusions (n=246) with available angiography runs between every
      manoeuvre was performed. Final reperfusion success and those between all single
      manoeuvres were evaluated applying the modified version of the TICI score
      (including TICI2c). Final TICI2c/3 reperfusions were dichotomized as 'direct'
      (reperfusion before final manoeuvre <=mTICI2a) or 'secondary improved' (mTICI2b
      was achieved). RESULTS: Patients with mTICI2c reperfusion had similar outcome to
      patients with mTICI3 rather than mTICI2b reperfusions. Compared with mTICI2c/3
      patients, mTICI2b-patients had lower rates of neurological improvement (33.3% vs.
      61.2%, p<0.001) and good functional outcome (28.7% vs. 46.5%, p=0.008). In 28
      patients, mTICI2b reperfusion was improved to mTICI2c/3 without complications.
      Outcome of patients with 'direct' or 'secondary improved' mTICI2c/3 did not
      differ (p>0.5). CONCLUSION: Improving mTICI2b reperfusions to mTICI2c/3
      reperfusions is sometimes technically feasible and safe, and associated with
      clinical benefit comparable to 'direct' mTICI2c/3 reperfusions. If confirmed, a
      more aggressive treatment approach in cases of already achieved mTICI2b may be
      justified, although proper patient selection is needed. KEY POINTS: * Patients
      with mTICI2c or 3 reperfusions have a comparable clinical course. * mTICI2c/3 are
      associated with a larger therapeutic benefit than are mTICI2b reperfusions. *
      Improving reperfusion from mTICI2b to mTICI2c/3 is sometimes feasible and
      reasonably safe. * Outcome of patients with 'secondary improved' and 'direct'
      mTICI2c/3 is not different.

PMID- 28752217
TI  - Non-invasive monitoring of the therapeutic response in sorafenib-treated
      hepatocellular carcinoma based on photoacoustic imaging.
AB  - PURPOSE: We investigated the changes of tissue oxygen saturation (sO2) in
      sorafenib-treated HCC (hepatocelluar carcinoma) mouse models using photoacoustic
      imaging (PI). MATERIALS AND METHODS: Nude mice, implanted with human HCC (HepG2
      RFP) cells in the liver, were randomised to the sorafenib-treated group (n = 21)
      or the control group (n = 20). Tumour volume and sO2 were measured by PI at
      baseline and then one week later, and radiant efficiency (RE) and therapeutic
      response were analysed by fluorescence imaging and histologic analysis. RESULTS:
      Sorafenib was effective in treating HCC by evaluating necrotic fraction,
      apoptosis index, and microvessel density (MVD). One week after treatment, the sO2
      of HCC and residual healthy liver tissue decreased, and the hypoxia inducible
      factor-1alpha (HIF-1alpha) protein expression of HCC increased, correlating with
      the apoptosis index. The DeltasO2 in HCC showed a significantly positive
      correlation with the necrotic fraction and the apoptosis index of tumour and a
      negative correlation with the MVD of tumour. CONCLUSION: Sorafenib treatment
      results in changes of sO2 in HCC and liver parenchyma and induces the
      accumulation of HIF-1alpha by hypoxic environment. sO2 as measured by PI, can be
      a useful marker for non-invasive monitoring of the therapeutic response in
      orthotopic HCC mouse models. KEY POINTS: * Hypoxia is a characteristic feature of
      the tumour microenvironment * It is important to monitor sO 2 in HCC during
      sorafenib treatment * PI is useful for non-invasive monitoring of sO 2 in HCC. *
      DeltasO 2 in HCC showed a significantly correlation with tumour response.

PMID- 28752218
TI  - Predicting IDH mutation status of intrahepatic cholangiocarcinomas based on
      contrast-enhanced CT features.
AB  - OBJECTIVES: To explore the difference in contrast-enhanced computed tomography
      (CT) features of intrahepatic cholangiocarcinomas (ICCs) with different
      isocitrate dehydrogenase (IDH) mutation status. METHODS: Clinicopathological and
      contrast-enhanced CT features of 78 patients with 78 ICCs were retrospectively
      analysed and compared based on IDH mutation status. RESULTS: There were 11 ICCs
      with IDH mutation (11/78, 14.1%) and 67 ICCs without IDH mutation (67/78, 85.9%).
      IDH-mutated ICCs showed intratumoral artery more often than IDH-wild ICCs (p =
      0.023). Most ICCs with IDH mutation showed rim and internal enhancement (10/11,
      90.9%), while ICCs without IDH mutation often appeared diffuse (26/67, 38.8%) or
      with no enhancement (4/67, 6.0%) in the arterial phase (p = 0.009). IDH-mutated
      ICCs showed significantly higher CT values, enhancement degrees and enhancement
      ratios in arterial and portal venous phases than IDH-wild ICCs (all p < 0.05).
      The CT value of tumours in the portal venous phase performed best in
      distinguishing ICCs with and without IDH mutation, with an area under the curve
      of 0.798 (p = 0.002). CONCLUSIONS: ICCs with and without IDH mutation differed
      significantly in arterial enhancement mode, and the tumour enhancement degree on
      multiphase contrast-enhanced CT was helpful in predicting IDH mutation status.
      KEY POINTS: * IDH mutation occurred frequently in ICCs. * ICCs with and without
      IDH mutation differed significantly in arterial enhancement mode. * ICCs with IDH
      mutation enhanced more than those without IDH mutation. * Enhancement ratio and
      tumour CT value can predict IDH mutation status.

PMID- 28752220
TI  - A patient with mitochondrial disorder due to a novel mutation in MRPS22.
AB  - MRPS22 gene defect is a very rare newly discovered mitochondrial disorder. We
      report a 4-month-old severely affected male infant with MRPS22 mutation. Whole
      exome sequencing revealed a novel homozygous splicing mutation c.339 + 5 G > A in
      MRPS22 gene. He has mild dysmorphism, hypotonia, developmental delay but not
      hypertrophic cardiomyopathy and tubulopathy which differ from other majority of
      reported patients. Therefore, hypertrophic cardiomyopathy and tubulopathy may not
      be considered as constant features of MRPS22. With this case report, we also
      present first symmetrical bilateral brainstem and medial thalamic lesions, and
      cerebellar and cerebral atrophy on a brain MR imaging follow-up of ten months.

PMID- 28752219
TI  - The putative role of environmental aluminium in the development of chronic
      neuropathology in adults and children. How strong is the evidence and what could
      be the mechanisms involved?
AB  - The conceptualisation of autistic spectrum disorder and Alzheimer's disease has
      undergone something of a paradigm shift in recent years and rather than being
      viewed as single illnesses with a unitary pathogenesis and pathophysiology they
      are increasingly considered to be heterogeneous syndromes with a complex
      multifactorial aetiopathogenesis, involving a highly complex and diverse
      combination of genetic, epigenetic and environmental factors. One such
      environmental factor implicated as a potential cause in both syndromes is
      aluminium, as an element or as part of a salt, received, for example, in oral
      form or as an adjuvant. Such administration has the potential to induce pathology
      via several routes such as provoking dysfunction and/or activation of glial cells
      which play an indispensable role in the regulation of central nervous system
      homeostasis and neurodevelopment. Other routes include the generation of
      oxidative stress, depletion of reduced glutathione, direct and indirect
      reductions in mitochondrial performance and integrity, and increasing the
      production of proinflammatory cytokines in both the brain and peripherally. The
      mechanisms whereby environmental aluminium could contribute to the development of
      the highly specific pattern of neuropathology seen in Alzheimer's disease are
      described. Also detailed are several mechanisms whereby significant quantities of
      aluminium introduced via immunisation could produce chronic neuropathology in
      genetically susceptible children. Accordingly, it is recommended that the use of
      aluminium salts in immunisations should be discontinued and that adults should
      take steps to minimise their exposure to environmental aluminium.

PMID- 28752222
TI  - High Grade T1 Papillary Urothelial Bladder Cancer Shows Prominent Peritumoral
      Retraction Clefting.
AB  - Differentiation of noninvasive from invasive papillary urothelial carcinoma can
      be challenging due to inability of proper orientation and thermal damage of
      transurethrally obtained material. The aim of this study was to analyze the
      presence and extent of peritumoral retractions in pT1 compared to pTa papillary
      urothelial carcinoma. Since peritumoral retractions may result from altered
      expression profiles of extracellular matrix proteins, we additionally analyzed
      the expression of matrix metalloproteinase 2 (MMP-2) and interleukin 8 (IL-8) in
      these tumors. The study comprised 50 noninvasive (pTa) and 50 invasive (pT1)
      cases of transurethrally obtained primary papillary urothelial carcinomas. The
      invasive nature of nests showing peritumoral retractions was confirmed
      immunohistochemically using antibody against collagen IV. Staining for MMP-2 and
      IL-8 was evaluated semiquantitatively using immunohistochemical staining index,
      calculated by multiplying the percentage of positive cells and staining
      intensity. Peritumoral retractions were found in 32% of pT1 carcinomas but in
      none of the pTa carcinomas. All tumors showing peritumoral retraction were high
      grade tumors. There was no statistically significant correlation between the
      expression of MMP-2 or IL-8 and the presence of peritumoral retractions or stage
      of the tumor (pTa vs. pT1). A statistically significant but weak correlation was
      found between MMP-2 and IL-8 expression (chi2-test, p=0,015). There was no
      statistically significant correlation between the presence of peritumoral
      retractions or MMP-2 expression and tumor recurrence and progression. Our study
      shows that, in doubtful cases, when differentiating between pTa and pT1 stages of
      papillary urothelial carcinoma, the presence of peritumoral retractions could
      favor the diagnosis of invasive neoplasm.

PMID- 28752221
TI  - DNA methylation profiles in cancer diagnosis and therapeutics.
AB  - Cancer initiation and proliferation is regulated by both epigenetic and genetic
      events with epigenetic modifications being increasingly identified as important
      targets for cancer research. DNA methylation catalyzed by DNA methyltransferases
      (DNMTs) is one of the essential epigenetic mechanisms that control cell
      proliferation, apoptosis, differentiation, cell cycle, and transformation in
      eukaryotes. Recent progress in epigenetics revealed a deeper understanding of the
      mechanisms of tumorigenesis and provided biomarkers for early detection,
      diagnosis, and prognosis in cancer patients. Although DNA methylation biomarker
      possesses potential contributing to precision medicine, there are still
      limitations to be overcome before it reaches clinical setting. Hence, the current
      status of DNA methylation biomarkers was reviewed and the future use in clinic
      was also predicted.

PMID- 28752223
TI  - Discrete-choice modelling of patient preferences for modes of drug
      administration.
AB  - The administration of (biologically-derived) drugs for various disease conditions
      involves consumption of resources that constitutes a direct monetary cost to
      healthcare payers and providers. An often ignored cost relates to a mismatch
      between patients' preferences and the mode of drug administration. The
      "intangible" benefits of giving patients what they want in terms of the mode of
      drug delivery is seldom considered. This study aims to evaluate, in monetary
      terms, end-user preferences for the non-monetary attributes of different modes of
      drug administration using a discrete-choice experiment. It provides empirical
      support to the notion that there are significant benefits from developing patient
      friendly approaches to drug delivery. The gross benefits per patient per unit
      administration is in the same order of magnitude as the savings in resource costs
      of administering drugs. The study argues that, as long as the underlying
      manufacturing science is capable, a patient-centred approach to producing drug
      delivery systems should be encouraged and pursued.

PMID- 28752224
TI  - Early Preclinical Changes in Hippocampal CREB-Binding Protein Expression in a
      Mouse Model of Familial Alzheimer's Disease.
AB  - The molecular basis of memory loss in Alzheimer's disease (AD), the main cause of
      senile dementia, is under investigation. In the present study, we have focused on
      the early hippocampal memory-related changes in APPswe/PS1dE9 (APP/PS1) mice, a
      well-established mouse model of familial AD. It is well known that molecules like
      cAMP response element binding (CREB) and binding protein (CBP) play a crucial
      role in memory consolidation. We analyzed CBP on its transcriptional activity and
      protein levels, finding a significant downregulation of both of them at 3-month
      old mice. In addition, the downregulation of this molecule was associated with a
      decrease on acetylation levels of histone H3 in the hippocampus of APP/PS1 mice.
      Moreover, the p-CREB levels, which are important for memory acquisition at 3
      months in APP/PS1 mice, were downregulated. Furthermore, we suggest that early
      neuroinflammation, especially due to the Tnfalpha gene increased expression,
      could also be responsible to this process of memory loss. Given all the
      previously mentioned results, we propose that an early suitable treatment to
      prevent the evolution of the disease should include a combination of drugs,
      including anti-inflammatories, which may decrease glial activation and Tnfalpha
      levels, and phosphodiesterase inhibitors that increase cAMP levels.

PMID- 28752225
TI  - Grading and outcome prediction of pediatric diffuse astrocytic tumors with
      diffusion and arterial spin labeling perfusion MRI in comparison with 18F-DOPA
      PET.
AB  - PURPOSE: The aim of this study was to investigate MRI-derived diffusion weighted
      imaging (DWI) and arterial spin labeling (ASL) perfusion imaging in comparison
      with 18F-dihydroxyphenylalanine (DOPA) PET with respect to diagnostic performance
      in tumor grading and outcome prediction in pediatric patients with diffuse
      astrocytic tumors (DAT). METHODS: We retrospectively analyzed 26 children with
      histologically proven treatment naive low and high grade DAT who underwent ASL
      and DWI performed within 2 weeks of 18F-DOPA PET. Relative ASL-derived cerebral
      blood flow max (rCBF max) and DWI-derived minimum apparent diffusion coefficient
      (rADC min) were compared with 18F-DOPA uptake tumor/normal tissue (T/N) and
      tumor/striatum (T/S) ratios, and correlated with World Health Organization (WHO)
      tumor grade and progression-free survival (PFS). Statistics included Pearson's
      chi-square and Mann-Whitney U tests, Spearman's rank correlation, receiver
      operating characteristic (ROC) analysis, discriminant function analysis (DFA),
      Kaplan-Meier survival curve, and Cox analysis. RESULTS: A significant correlation
      was demonstrated between rCBF max, rADC min, and 18F-DOPA PET data (p < 0.001).
      Significant differences in terms of rCBF max, rADC min, and 18F-DOPA uptake were
      found between low- and high-grade DAT (p <= 0.001). ROC analysis and DFA
      demonstrated that T/S and T/N values were the best parameters for predicting
      tumor progression (AUC 0.93, p < 0.001). On univariate analysis, all diagnostic
      tools correlated with PFS (p <= 0.001); however, on multivariate analysis, only
      18F-DOPA uptake remained significantly associated with outcome (p <= 0.03), while
      a trend emerged for rCBF max (p = 0.09) and rADC min (p = 0.08). The combination
      of MRI and PET data increased the predictive power for prognosticating tumor
      progression (AUC 0.97, p < 0.001). CONCLUSIONS: DWI, ASL and 18F-DOPA PET provide
      useful complementary information for pediatric DAT grading. 18F-DOPA uptake
      better correlates with PFS prediction. Combining MRI and PET data provides the
      highest predictive power for prognosticating tumor progression suggesting a
      synergistic role of these diagnostic tools.

PMID- 28752226
TI  - Highlights of articles published in annals of nuclear medicine 2016.
AB  - This article is the first installment of highlights of selected articles
      published during 2016 in the Annals of Nuclear Medicine, an official peer
      reviewed journal of the Japanese Society of Nuclear Medicine. A companion article
      highlighting selected articles published during 2016 in the European Journal of
      Nuclear Medicine and Molecular Imaging, which is the official peer-reviewed
      journal of the European Association of Nuclear Medicine, will also appear in the
      Annals Nuclear Medicine. This new initiative by the respective journals will
      continue as an annual endeavor and is anticipated to not only enhance the
      scientific collaboration between Europe and Japan but also facilitate global
      partnership in the field of nuclear medicine and molecular imaging.

PMID- 28752227
TI  - Feasibility of ultrasound-guided vascular access during cardiac implantable
      device placement.
AB  - PURPOSE: Ultrasound (US)-guided access for venous catheter placement has
      previously been shown to improve success rates and decrease access-related
      complications. The purpose of this study was to determine the feasibility of US
      guided versus traditional vascular access approaches during implantation of
      cardiac implantable electronic devices (CIEDs). METHODS: We evaluated outcomes
      for 816 consecutive patients undergoing new CIED implantation between May 2013
      and April 2016 at a single institution with respect to use of US guidance for
      vascular access (137 with US guidance versus 679 with traditional access
      techniques). The primary outcome was a composite of procedural complications
      including deep vein thrombosis, pneumothorax, or hematoma. RESULTS: There was no
      cross-over between US guidance and traditional access. The overall complication
      rate was 3.6% (2.2% in US, 3.8% in non-US). The use of US was associated with a
      decrease in fluoroscopy time (r = -0.17, p < 0.01) but not the primary outcome (r
      = 0.03, p = 0.34). In models adjusted for age and number of leads, use of US was
      non-significantly associated with a change in fluoroscopy time (beta = -0.20, p =
      0.7). In logistic models adjusted for age and number of leads, use of US was
      associated with a trend toward reduced major complications (OR = 0.57, 95% CI
      0.17-1.91, p = 0.36). CONCLUSIONS: US-guided vascular access for CIED
      implantation is safe and effective compared to traditional approaches with a non
      significant reduction in both fluoroscopy time and procedural complications.

PMID- 28752228
TI  - The Dx-AF study: a prospective, multicenter, randomized controlled trial
      comparing VDD-ICD to VVI-ICD in detecting sub-clinical atrial fibrillation in
      defibrillator patients.
AB  - PURPOSE: Atrial fibrillation (AF) is the most common cardiac dysrhythmia.
      Appropriate detection of AF and early initiation of oral anticoagulation therapy
      are critical to reduce the risk of stroke. Patients with implantable cardioverter
      defibrillators (ICD) are at high risk of developing AF. The purpose of the Dx-AF
      study is to demonstrate that a novel single-lead VDD-ICD system (Linox smart S
      DX) will facilitate adequate recognition of sub-clinical AF and ultimately stroke
      prevention with a comparable safety profile in comparison to VVI-ICD. METHODS AND
      RESULTS: Dx-AF is a prospective, randomized controlled, open-label trial.
      Patients who are indicated to receive a single-chamber ICD will be randomized to
      a VDD-ICD (experimental group) or single-chamber ICD (control group). We have
      used a sample size of 355, which after generous allowance for loss-to-follow-up,
      yields a sample size of 378 patients at up to 13 Canadian sites. The trial will
      enroll patients with ischemic or non-ischemic cardiomyopathy, age > 50 years,
      LVEF < 50%, scheduled for primary or secondary prevention single-chamber ICD,
      with no ECG-documented history of AF or flutter. The primary (efficacy) outcome
      of this study will be the time to the first detected and confirmed episode of AF
      or atrial flutter lasting at least 6 min. The secondary (safety) outcome will be
      a composite outcome of serious device-related complications. The proposed follow
      up period in this trial will be 36 months after randomization. CONCLUSIONS: The
      Dx-AF Study should provide significant scientific evidence and guidance to an
      adequate ICD system choice and early AF detection/management hence improve
      clinical outcomes in a large patient population.

PMID- 28752229
TI  - Hope Modules: Brief Psychotherapeutic Interventions to Counter Demoralization
      from Daily Stressors of Chronic Illness.

PMID- 28752231
TI  - Parasites and pathological conditions in the edible oyster, Crassostrea
      madrasensis (Preston), from the east and west coasts of India.
AB  - A detailed pathological survey was carried out on the commercially important
      edible oyster, Crassostrea madrasensis (Preston), from two distinct
      coastal/brackish water ecosystems of south India. Samples were collected twice a
      year during wet and dry seasons from 2009 to 2012. Bacterial colonies in the form
      of prokaryotic inclusions, protozoans (Perkinsus beihaiensis, Nematopsis sp. and
      ciliates Sphenophrya sp. and Stegotricha sp.), metazoans (trematodes,
      turbellaria, cestodes and crustaceans) and shell parasites (Polydora spp. and
      Cliona spp.) along with various pathological conditions (digestive tubule
      atrophy, ceroid bodies, haemocytic infiltration, tissue necrosis and neoplastic
      disorders) were observed in C. madrasensis collected from two sites. Intensity,
      spatial and seasonal variations in infection prevalence and pathological effects
      on the host were studied. The protozoan parasite, P. beihaiensis; shell parasite,
      Polydora spp. and pathological condition, digestive gland atrophy were most
      prevalent in occurrence. High-intensity infections with P. beihaiensis, larval
      trematodes and Polydora spp. were found to cause significant impact on host
      physiology. All other parasites were observed with low mean prevalence and
      intensity. Karapad in Tuticorin bay, the site reported with marked pollution
      levels, exhibited higher number of parasitic taxa and high mean prevalence and
      intensity for pathological conditions.

PMID- 28752230
TI  - Biological therapies for the treatment of Behcet's disease-related uveitis beyond
      TNF-alpha blockade: a narrative review.
AB  - Intraocular inflammation is one of the more relevant complications of Behcet's
      disease (BD), which tends to respond poorly to different medications. The ocular
      histopathologic changes are basically identical to those occurring in other
      organs and consist in a necrotizing leukocytoclastic obliterative vasculitis,
      which is probably immune complex-mediated and affects both arteries and veins of
      all sizes. There are growing evidences showing the potential role of biologic
      agents other than anti-tumor necrosis factor (TNF)-alpha agents in the management
      of ocular-BD, which have been collected in this review, including interleukin-1
      and interleukin-6 blockade, secukinumab, ustekinumab, daclizumab, rituximab, and
      alemtuzumab. Further large studies are needed to fully elucidate and establish
      the clinical efficacy of these different tools in the refractory ocular
      manifestations of BD.

PMID- 28752232
TI  - Urethral prolapse in a paediatric patient with urogenital bleeding: diagnosis by
      imaging.

PMID- 28752233
TI  - Upper limb lymphedema in breast cancer patients in the era of Z0011, sentinel
      lymph node biopsy and breast conservation.
AB  - INTRODUCTION: Surgical techniques in breast cancer (BCa) have seen a dramatic
      change recently with breast-conserving surgery (BCS) and sentinel lymph node
      biopsy (SLNB). The ACOSOG-Z0011 trial reported equivalence in outcomes for
      certain patients with SLN metastases treated with axillary lymph node dissection
      (ALND) or SLNB alone. Our aim was to investigate changes in lymphedema referral
      patterns in BCa patients over the last 3 years in a specialist unit and to
      elucidate effects of SLNB, BCS, and Z0011 trial publication on such patterns.
      METHODS: A retrospective study was performed over a 3-year period (May 2012-May
      2015). Patients were identified using a prospectively maintained lymphedema
      database and newly referred BCa patients with data availability were included.
      RESULTS: Overall lymphedema incidence was 11% (19.2% in ALND and 5.1% in SLNB
      cohort). There was a statistically significant difference in lymphedema referral
      patterns after Z0011, new referrals reduced by 20% (chi-sq; p = 0.001). Volume of
      referrals post ALND was reduced by 40% with concomitant 31% rise in those post
      SLNB alone, reflecting changing surgical patterns. There was a significant change
      in extent of lymphnode dissection during ALND (p = 0.003). CONCLUSION: The Z0011
      trial in association with wider implementation of SLNB has led to significant
      changes in the lymphedema referral patterns and extent of ALND.

PMID- 28752234
TI  - Implementing a tobacco-free hospital campus in Ireland: lessons learned.
AB  - BACKGROUND: The Irish Health Service Executive (HSE) had set a target that all
      HSE facilities should implement the HSE Tobacco Free Campus (TFC) policy by 2015.
      AIM: The aims of this study are to examine hospital staff awareness and to assess
      the progress of selected HSE health care facilities towards a TFC policy.
      METHODS: Three health care facilities that were conveniently located were self
      selected in County Cork, namely, an acute hospital, a mental health service and
      an older person's facility. Three different types of quantitative data were
      collected between May and September 2016 drawn on Standards 3, 4 and 5 of the
      European Network for Tobacco Free Health Care Services (ENSH-Global) tools: (1)
      face-to-face consultation with health care facility managers on their progress
      towards the HSE TFC policy, (2) self-administered questionnaire to a purposive
      sample of 153 staff members across three health care facilities and (3) physical
      observation of signs of smoking and smoking-related information across each
      health care facility for objective verification of compliance. RESULTS: Of the
      153 staff who completed the questionnaire, 64% were females, 39% were nurses, 20%
      were smokers and 76% agreed with the TFC policy. However, only 26% of the 153
      staff had received training on motivational and tobacco cessation techniques.
      Seventy-seven percent of the 153 staff stated that the campus was not tobacco
      free. Physical observation suggested signs of smoking within the campus across
      all three health care facilities surveyed. CONCLUSION: Staff awareness of the HSE
      TFC policy across selected health care facilities in Ireland is positive but is
      not sufficient. There are gaps in the implementation process of the HSE TFC
      policy in the health care facilities. Therefore, proper communication on the
      importance of the ENSH-Global standards and cessation training to all staff is
      necessary to help reduce smoking rates across the health care facilities and also
      to move towards a Tobacco Free Campus in Ireland.

PMID- 28752235
TI  - Prognostic implications of human papillomavirus status for patients with non
      oropharyngeal head and neck squamous cell carcinomas.
AB  - PURPOSE: We examined overall survival in a large cohort of patients with human
      papillomavirus (HPV)-positive and HPV-negative non-oropharyngeal squamous cell
      carcinoma of the head and neck (non-OPSCC). METHODS: Patients diagnosed with non
      OPSCC and known HPV status were identified in the National Cancer Database
      (NCDB). Multivariate logistic regression was applied to examine factors
      associated with HPV status. Multivariate analysis was utilized to determine
      factors correlated with overall survival. Propensity score-weighted Kaplan-Meier
      estimation was used to adjust for confounders in survival analyses. Multiple
      imputation method was used for sensitivity analysis. RESULTS: We identified
      19,993 non-OPSCC patients with 5070 being positive for HPV in the NCDB. Median
      follow-up was 23.5 months. HPV-positive patients were more commonly male, white,
      with a lower comorbidity index score, presenting with T-stage <2, and N-stage
      >=1. Unadjusted 3-year overall survival was 62% and 80% for HPV-negative and HPV
      positive patients, respectively (p < 0.0001). On multivariate analysis, mortality
      was reduced for HPV-positive patients with early stage (HR = 0.68) and locally
      advanced disease (HR = 0.46). Adjusted 3-year overall survival was 65% for HPV
      negative and 76% for HPV-positive patients (p < 0.0001). The survival advantage
      of HPV was maintained in all subsites and robust on sensitivity analysis.
      CONCLUSIONS: Patients with HPV-positive non-OPSCC exhibit similar characteristics
      as HPV-positive OPSCC. Overall survival was significantly higher for patients
      with HPV-positive versus HPV-negative non-OPSCC. These data reveal that HPV
      positive non-OPSCC represent a favorable cohort that warrants recognition in the
      design of future clinical trial investigation.

PMID- 28752236
TI  - Opa interacting protein 5 acts as an oncogene in bladder cancer.
AB  - PURPOSE: To explore the biological functions and mechanism of Opa interacting
      protein 5 (OIP5) in bladder cancer (BC). METHODS: We investigated the expression
      of OIP5 in BC through immunohistochemical staining (IHC) and its correlation with
      clinicopathologic features of BC patients. Moreover, knockdown of OIP5 was
      performed in BC cell lines and colony formation capacity, cell growth curve, cell
      cycle phase and cell apoptosis assay was applied for investigating the roles of
      OIP5 in BC. Moreover, the expression of OIP5 was validated through the Cancer
      Genome Atlas (TCGA) database. The diagnosis value of OIP5 was accessed by
      receiver operating characteristic (ROC) analysis in TCGA database. RESULTS: The
      expression of OIP5 in BC tissues was significantly higher than that in adjacent
      non-tumor tissues and bladder mucosa tissues with chronic cystitis. Higher
      protein expression level of OIP5 predicted shorter survival time in patients with
      BC, which was significantly correlated with larger tumor size, high-grade tumor
      and advanced T classification. The expression of OIP5 was considerably decreased
      after lentivirus infection both at mRNA and protein levels. Functional assay
      displayed that silencing of OIP5 inhibited colony formation capacity and cell
      growth in BC cell lines. Cell cycle assays indicated that suppressed OIP5
      disturbed the balance of the cell cycle in BC cell lines, which increased the
      cell population of the G1 phase and decreased the cell population of the S phase.
      Furthermore, knockdown of OIP5 expression enhanced cell apoptosis process. The
      expression of OIP5 was significantly up-regulated in BC compared with adjacent
      non-tumor tissues based on TCGA database. OIP5 had the potential diagnostic value
      for BC. CONCLUSIONS: Our work demonstrated that OIP5 might function as an
      oncogene to promote colony formation capacity and cell growth, arrest cell cycle
      and suppress cell apoptosis in bladder cancer.

PMID- 28752237
TI  - "Making My Own Decisions Sometimes": A Pilot Study of Young Adult Cancer
      Survivors' Perspectives on Medical Decision-Making.
AB  - This study aimed to provide a better understanding of the medical decision-making
      preferences and experiences of young adult survivors of pediatric, adolescent,
      and young adult cancers. We conducted key informant interviews and a cross
      sectional mailed survey with young adult survivors (currently aged 18-39 years)
      of pediatric, adolescent, and young adult cancers in South Texas. Of the
      responding survivors, almost all wanted to be actively involved in medical
      decision-making, but preferences regarding family and doctor involvement varied.
      In open-ended responses, the most commonly reported concerns related to medical
      decision-making were feelings of uncertainty and fear of receiving bad news.
      Survivors reported that they desired more information in order to feel better
      about medical decision-making. Due to the variety of preferences regarding
      decision-making and who to include in the process, physicians should be prepared
      to ask and accommodate patients regarding their decision-making preferences.

PMID- 28752238
TI  - Exome sequencing reveals a novel homozygous mutation in ACP33 gene in the first
      Italian family with SPG21.

PMID- 28752240
TI  - Preliminary screening of polybrominated diphenyl ethers (PBDEs),
      hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA) flame retardants
      in landfill leachate.
AB  - The occurrence of selected brominated flame retardants, including nine
      polybrominated diphenyl ether (PBDE) congeners, hexabromocyclododecane (HBCDD)
      and tetrabromobisphenol A (TBBPA) in leachate samples from eight landfill sites
      in South Africa, were investigated. In addition, the possible influences of
      dissolved organic carbon on their levels were also evaluated. Filtered leachate
      samples were subjected to solid-phase extraction to isolate the various target
      compounds. PBDEs with six bromine substituents and above, as well as alpha-HBCDD,
      beta-HBCDD and TBBPA, were generally found below the detection limit. However,
      the mean value of the total lower PBDE congeners ranged between 0.04 and 0.48 MUg
      L-1, and the concentrations of gamma-HBCDD ranged from not detectable (ND) to
      0.05 MUg L-1. No significant correlation was observed between the target
      compounds and dissolved organic carbon, although weak to moderate correlations
      were mostly observed for the lower PBDEs.

PMID- 28752239
TI  - Biometeorology for cities.
AB  - Improvements in global sustainability, health, and equity will largely be
      determined by the extent to which cities are able to become more efficient,
      hospitable, and productive places. The development and evolution of urban areas
      has a significant impact on local and regional weather and climate, which
      subsequently affect people and other organisms that live in and near cities.
      Biometeorologists, researchers who study the impact of weather and climate on
      living creatures, are well positioned to help evaluate and anticipate the
      consequences of urbanization on the biosphere. Motivated by the 60th anniversary
      of the International Society of Biometeorology, we reviewed articles published in
      the Society's International Journal of Biometeorology over the period 1974-2017
      to understand if and how biometeorologists have directed attention to urban
      areas. We found that interest in urban areas has rapidly accelerated; urban
      oriented articles accounted for more than 20% of all articles published in the
      journal in the most recent decade. Urban-focused articles in the journal span
      five themes: measuring urban climate, theoretical foundations and models, human
      thermal comfort, human morbidity and mortality, and ecosystem impacts. Within
      these themes, articles published in the journal represent a sizeable share of the
      total academic literature. More explicit attention from urban biometeorologists
      publishing in the journal to low- and middle-income countries, indoor
      environments, animals, and the impacts of climate change on human health would
      help ensure that the distinctive perspectives of biometeorology reach the places,
      people, and processes that are the foci of global sustainability, health, and
      equity goals.

PMID- 28752241
TI  - Aeolian process of the dried-up riverbeds of the Hexi Corridor, China: a wind
      tunnel experiment.
AB  - Wind tunnel studies, which remain limited, are an important tool to understand
      the aeolian processes of dried-up riverbeds. The particle size, chemical
      composition, and the mineral contents of sediments arising from the dried river
      beds are poorly understood. Dried-up riverbeds cover a wide area in the Hexi
      Corridor, China, and comprise a complex synthesis of different land surfaces,
      including aeolian deposits, pavement surfaces, and Takyr crust. The results of
      the present wind tunnel experiment suggest that aeolian transport from the dried
      up riverbeds of the Hexi Corridor ranges from 0 to 177.04 g/m2/min and that dry
      riverbeds could be one of the main sources of dust emissions in this region. As
      soon as the wind velocity reaches 16 m/s and assuming that there are abundant
      source materials available, aeolian transport intensity increases rapidly. The
      dried-up riverbed sediment and the associated aeolian transported material were
      composed mainly of fine and medium sands. However, the transported samples were
      coarser than the bed samples, because of the sorting effect of the aeolian
      processes on the sediment. The aeolian processes also led to regional elemental
      migration and mineral composition variations.

PMID- 28752242
TI  - Patients' Understanding and Attitudes Towards Infliximab and Etanercept
      Biosimilars: Result of a UK Web-Based Survey.
AB  - BACKGROUND: Infliximab and etanercept biosimilars present significant potential
      cost savings to the NHS. Patients need to be involved in the decision to use
      these medicines but there is limited published literature on their knowledge and
      attitudes about these biosimilars. OBJECTIVES: The aim of this study was to
      investigate ankylosing spondylitis and rheumatoid arthritis patients' knowledge
      and attitudes towards infliximab and etanercept biosimilars in the UK. METHODS: A
      self-administered web survey was conducted among the members of the National
      Rheumatoid Arthritis Society and the National Ankylosing Spondylitis Society in
      the UK between 2 March 2017 and 2 June 2017. RESULTS: A total of 182 patients
      participated in this survey. The majority of participants (73%) were on
      etanercept, and 66 and 80% of patients on originator biologic and biosimilars,
      respectively, understood what biosimilars were. Patients who were currently on
      biosimilars had greater confidence in their effectiveness and the doctor's
      decision to initiate than those who were originally on originator biologics that
      doctors proposed to switch to biosimilars. The majority (82%) of participants on
      biosimilars thought that biosimilars help to save money for the NHS, while just
      over half (54%) of participants on the originator biologics thought the cost of
      treatment should not be considered when prescribing biosimilars. CONCLUSIONS:
      Survey participants had a good knowledge and understanding of biosimilars.
      Participants on biosimilars were confident and positive about biosimilars'
      safety, efficacy and switching, whereas participants on the originator biologics
      were more reluctant to switch to biosimilars. Those patients who expressed
      concerns felt that more clinical trials on switching biosimilars, better
      communication and reassurance by healthcare professional teams and further
      involvement in decision making would increase their acceptance of biosimilars.

PMID- 28752243
TI  - Design of mulitlevel OLF approach ("V"-shaped decompressive laminoplasty) based
      on 3D printing technology.
AB  - PURPOSE: To introduce a new surgical approach to the multilevel ossification of
      the ligamentum flavum (OLF) aided by three-dimensional (3D) printing technology.
      METHODS: A multilevel OLF patient (male, 66 years) was scanned using computed
      tomography (CT). His saved DICOM format data were inputted to the Mimics14.0 3D
      reconstruction software (Materialise, Belgium). The resulting 3D model was used
      to observe the anatomical features of the multilevel OLF area and to design the
      surgical approach. At the base of the spinous process, two channels were created
      using an osteotomy bilaterally to create a "V" shape to remove the bone
      ligamentous complex (BLC). The decompressive laminoplasty using mini-plate
      fixation was simulated with the computer. The physical model was manufactured
      using 3D printing technology. The patient was subsequently treated using the
      designed surgery. RESULT: The operation was completed successfully without any
      complications. The operative time was 90 min, and blood loss was 200 ml. One
      month after the operation, neurologic function was recovered well, and the JOA
      score was improved from 6 preoperatively to 10. Postoperative CT scanning showed
      that the OLF was totally removed, and the replanted BLC had not subsided.
      CONCLUSION: 3D printing technology is an effective, reliable, and minimally
      invasive method to design operations. The technique can be an option for
      multilevel OLF surgical treatment. This can provide sufficient decompression with
      minimum damage to the spine and other intact anatomical structures.

PMID- 28752244
TI  - Accuracy of 3D fluoro-navigated anterior transpedicular screws in the subaxial
      cervical spine: an experimental study on human specimens.
AB  - INTRODUCTION: Pedicle screw stabilization, the standard technique in the thoracic
      and lumbar spine, is increasingly used in the cervical spine. Initial studies on
      the use of anterior pedicle screws (ATPS) in the cervical spine have been
      recently published. ATPS use has theoretical advantages over posterior
      stabilization. We have already established a 3D-fluoroscopy navigation setup in a
      study of artificial bones. The aim of the current study was to evaluate the
      positioning quality/accuracy of ATPS introduced to human specimens. METHODS: 36
      cannulated screws (3.5 mm) were implanted anteriorly into the C3-C7 segments of
      four spines (unfixed, frozen, cadaveric specimens) using a 3D-fluoroscopy
      navigation system. Placement accuracy was evaluated using a recently published
      classification on postoperative CT scans. Grade 1 is perfect position with
      pedicle wall perforation <1 mm, grade 2 is perforation <2 mm, etc., and finally
      grade 5 is cortical perforation of >4 mm and/or transverse foramen entry.
      RESULTS: 36 anterior pedicle screws were inserted into four human cervical spine
      specimens. Of these, seven screws were introduced to C3, five to C4 and eight
      each to C5, C6, and C7. Classified with the modified G&R, 21 of 36 (58.3%) were
      grade 1. Ten screws (27.8%) were grade 2. Grade 4 was assessed for two screws and
      grade 5 for three. Customary "good" positioning, combining grades 1 and 2, was
      thus found in 86.1%. Five screws (13.9%) did not meet this criterion (grade >=3).
      CONCLUSIONS: With 86.1% of good positioning (grade 2 or better), a 3D-fluoroscopy
      navigation of ATPS screws into human c-spine specimens achieved a satisfying
      results. These are at least comparable to results presented in the literature for
      posteriorly introduced subaxial pedicle screws.

PMID- 28752245
TI  - Which salvage fixation technique is best for the failed initial screw fixation at
      the cervicothoracic junction? A biomechanical comparison study.
AB  - PURPOSE: The pedicle screw construct is the most widely used technique for
      instrumentation at cervicothoracic junction (CTJ) because of its high
      biomechanical stability. However, we may need salvage fixation options for it as
      there might be a situation when pedicle screw is not available or it initially
      fails in order to obviate the need to instrument an additional motion segment. We
      aimed to evaluate the ability of using salvage screw fixations at CTJ (C7, T1,
      T2), when the initial fixation method fails. METHODS: Fifteen fresh-frozen
      cadaveric specimens (C7-T2) were tested for pull-out strength (POS, N) and
      insertion torque (IT, Nm) of three C7 fixation techniques (lateral mass, pedicle
      and laminar screw) and three upper thoracic spine instrumentation (pedicle screws
      with straight trajectory, anatomical trajectory pedicle screws and laminar
      screw). Data are shown as mean +/- standard deviation (SD). RESULTS: C7 pedicle
      screws generated statistically greater IT and POS than other C7 fixation
      techniques (P < 0.05). Similar trends were observed with pedicle fixation as a
      salvage procedure (P < 0.05). Laminar screws yielded significantly higher POS
      values than lateral mass fixation when applied as a salvage C7 fixation (mean
      POS: lateral mass screw-299.4 +/- 173.8 N, laminar screw-629.3 +/- 216.1, P =
      0.013). Significant relationship was established between IT and POS for all
      screws using Pearson correlation coefficient analysis (r = 0.624, P < 0.01).
      Pedicle screw with different trajectory (anatomical vs straightforward) did not
      show any significant difference in terms of POS as the initial and salvage
      fixation of upper thoracic spine. As a salvage fixation technique, there was no
      significant difference between laminar screw and a pedicle screw with different
      trajectory (P > 0.05). CONCLUSION: Laminar screws appear to provide stronger and
      more reproducible salvage fixation than lateral mass screws for C7 fixation, if
      pedicle screw should fail. If failure of initial pedicle screw is verified at the
      upper thoracic spine, both laminar screw and pedicle screw with different
      trajectory could be an option of salvage fixation. Our results suggest that
      pedicle screws and laminar screw similarly provide a strong fixation for salvage
      applications in the cervicothoracic junction.

PMID- 28752246
TI  - Myelopathy associated with instability consequent to resection of ossification of
      anterior longitudinal ligament in DISH.
AB  - PURPOSE: The presence of prominent OALL (ossification of anterior longitudinal
      ligament) in the anterior cervical spine has been implicated as a cause of
      dysphagia. Surgical resection of the OALL is considered effective for the
      management of diffuse idiopathic skeletal hyperostosis (DISH)-related dysphagia.
      Although many reports have been published on DISH-related dysphagia, no cases of
      postoperative cervical instability have been reported thus far. We present a case
      in which the patient developed myelopathy associated with instability consequent
      to resection of OALL in DISH. METHODS: A 62-year-old man presented with
      progressive dysphagia that persisted for a year. The patient's symptoms were
      successfully resolved by resection of OALL. Five years after the surgery, the
      dysphagia resurfaced and was found to be caused by the regrowth of the OALL. A
      repeat surgery was performed, and the dysphagia disappeared. Eleven months after
      the second surgery, he visited the hospital with progressive quadriparesis and
      pain in the cervical region. RESULTS: Nine-month follow-up radiologic study
      revealed cervical instability at the level of C5-6 resulting in myelopathy. The
      patient underwent decompressive laminectomy and posterior fusion surgery.
      CONCLUSION: Surgical resection of DISH-related dysphagia typically yields
      excellent outcomes, but our experience in this case highlights the possibility of
      OALL regrowth and subsequent cervical instability after resection of OALL.

PMID- 28752247
TI  - Breast cancer complexity: implications of intratumoral heterogeneity in clinical
      management.
AB  - Generation of intratumoral phenotypic and genetic heterogeneity has been
      attributed to clonal evolution and cancer stem cells that together give rise to a
      tumor with complex ecosystems. Each ecosystem contains various tumor cell
      subpopulations and stromal entities, which, depending upon their composition, can
      influence survival, therapy responses, and global growth of the tumor. Despite
      recent advances in breast cancer management, the disease has not been completely
      eradicated as tumors recur despite initial response to treatment. In this review,
      using data from clinically relevant breast cancer models, we show that the fates
      of tumor stem cells/progenitor cells in the individual tumor ecosystems
      comprising a tumor are predetermined to follow a limited (unipotent) and/or
      unlimited (multipotent) path of differentiation which create conditions for
      active generation and maintenance of heterogeneity. The resultant dynamic systems
      respond differently to treatments, thus disrupting the delicate stability
      maintained in the heterogeneous tumor. This raises the question whether it is
      better then to preserve stability by preventing takeover by otherwise dormant
      ecosystems in the tumor following therapy. The ultimate strategy for personalized
      therapy would require serial assessments of the patient's tumor for biomarker
      validation during the entire course of treatment that is combined with their
      three-dimensional mapping to the tumor architecture and landscape.

PMID- 28752249
TI  - [Treatment structures for men with pedosexual problems].
AB  - Pedophilia is defined as a persistent or dominating sexual preference for
      prepubescent children characterized by persistent thoughts, fantasies, urges,
      sexual arousal and behavior. Less than 50% of all child abusers fulfill the
      diagnostic criteria and an even smaller part exclusively has a preference for
      children. Following psychiatric classification systems, pedophilia must be
      distinguished from child sexual abuse. Outpatient treatment and treatment in
      forensic psychiatry clinics, sociotherapeutic facilities and in correction
      facilities are different aspects of prevention. So-called grey area projects
      (Dunkelfeldprojekte) are special facilities of primary and secondary prevention.
      The aim is to prevent sexual abuse by reducing and controlling of risk factors.

PMID- 28752250
TI  - [The roots of sexual medicine in Germany : A personal retrospective].
AB  - The first steps toward an academic sexual medicine were made half a century ago
      in the Federal Republic of Germany. After the so-called sexual revolution, the
      first approaches to an academicization of the field of sexual science were
      located in Hamburg and Frankfurt, where independent institutes and chairs were
      set up. Through empirical studies, the ignorance of physicians and medical
      students in sexuality-related topics could be demonstrated and subsequently
      addressed. In the early 1970s a journal named Sexualmedizin was founded, the
      first education courses for physicians in sexual medicine were held and in
      Frankfurt the first "special" university outpatient clinic in the country was
      opened with a department for sexual science. During the following decades,
      several textbooks were published and the professional training of physicians was
      expanded. As a university specialty, however, sexual medicine is still one of the
      most threatened medical subjects, being represented in only a few German
      faculties.Prof. Dr. Volkmar Sigusch, a pioneer of modern sexual research, looks
      back on events and personal experiences and gives an overview of the actors and
      sexual-scientific publications of the time.

PMID- 28752248
TI  - Antiplatelet agents for cancer treatment: a real perspective or just an echo from
      the past?
AB  - The association between coagulation and cancer development has been observed for
      centuries. However, the connection between inflammation and malignancy is also
      well-recognized. The plethora of evidence indicates that among multiple
      hemostasis components, platelets play major roles in cancer progression by
      providing surface and granular contents for several interactions as well as
      behaving like immune cells. Therefore, the anticancer potential of anti-platelet
      therapy has been intensively investigated for many years. Anti-platelet agents
      may prevent cancer, decrease tumor growth, and metastatic potential, as well as
      improve survival of cancer patients. On the other hand, there are suggestions
      that antiplatelet treatment may promote solid tumor development in a phenomenon
      described as "cancers follow bleeding." The controversies around antiplatelet
      agents justify insight into the subject to establish what, if any, role platelet
      directed therapy has in the continuum of anticancer management.

PMID- 28752251
TI  - A case of Kawasaki disease presenting as sigmoid colitis.
AB  - Initial gastrointestinal symptoms might confuse the clinical pictures of some
      patients with Kawasaki disease (KD) and delay diagnosis and treatment, especially
      when the patient does not fulfill sufficient diagnostic criteria for KD. Here, we
      present the case of a 4-year-old boy with KD who complained of severe left
      abdominal pain and fever alone for the first 6 days. Abdominal ultrasonography
      showed severe wall thickening localized to the sigmoid colon, and these findings
      were confirmed by computed tomography and colonoscopy. Microscopic examination of
      a biopsy specimen revealed non-specific colitis with inflammatory cells in the
      lamina propria of the sigmoid colon, indicating sigmoid colitis. He subsequently
      exhibited typical symptoms of KD and was successfully treated with oral
      administration of aspirin. We suggest that KD should be considered as a
      differential diagnosis in any child presenting with abdominal symptoms and
      prolonged fever without definable cause. Abdominal ultrasonography can help
      evaluate the gastrointestinal complications of KD.

PMID- 28752252
TI  - Prenatal diagnosis of pulmonary atresia with ventricular septal defect.
AB  - Pulmonary atresia with ventricular septal defect (PA-VSD) is a rare complex
      congenital heart defect. Major artery-pulmonary collateral arteries (MAPCAs) are
      characteristic of PA-VSD. Prenatal diagnosis can be achieved in most cases of PA
      VSD with recent advances in echocardiography. However, it is extremely rare that
      all MAPCAs can be observed on the echocardiograph. Here, we report a case of
      prenatally diagnosed type C PA-VSD in which all the MAPCAs could be seen on the
      echocardiograph, with the diagnosis supported by autopsy evidence.

PMID- 28752253
TI  - Homing in a tropical social wasp: role of spatial familiarity, motivation and
      age.
AB  - We captured foragers of the tropical social wasp Ropalidia marginata from their
      nests and displaced them at different distances and directions. Wasps displaced
      within their probable foraging grounds returned to their nests on the day of
      release although they oriented randomly upon release; however, wasps fed before
      release returned sooner, displaying nest-ward orientation. When displaced to
      places far from their nests, thus expected to be unfamiliar, only a third
      returned on the day of release showing nest-ward orientation; others oriented
      randomly and either returned on subsequent days or never. When confined within
      mosquito-net tents since eclosion and later released to places close to their
      nests (but unfamiliar), even fed wasps oriented randomly, and only older wasps
      returned, taking longer time. Thus, contrary to insects inhabiting less-featured
      landscapes, R. marginata foragers appear to have thorough familiarity with their
      foraging grounds that enables them to orient and home efficiently after passive
      displacement. Their initial orientation is, however, determined by an interaction
      of the information acquired from surrounding landscape and their physiological
      motivation. With age, they develop skills to home from unfamiliar places. Homing
      behaviour in insects appears to be influenced by evolutionarily conserved
      mechanisms and the landscape in which they have evolved.

PMID- 28752254
TI  - Interaction between C18 fatty acids and DOPE PEG2000 in Langmuir monolayers:
      effect of degree of unsaturation.
AB  - In this study, we address the effect of the cis-double bond in 1,2-dioleoyl-sn
      glycero-3-phosphoethanolamide-N-[methoxy(polyethylene glycol)-2000, DOPE PEG2000
      (DP), on the Langmuir monolayer of C18 fatty acids-namely, stearic acid (SA),
      oleic acid (L1), linoleic acid (L2), and linolenic acid (L3)-with the same head
      group but different degrees of saturation on their hydrocarbon chains. Negative
      values of Gibbs free energy of mixing (DeltaG mix) were obtained throughout the
      investigated ranges of the unsaturated C18 fatty-acid (L1, L2 and L3) mixed
      systems, indicating that very strong attractions occurred between molecules in
      the monolayers. The bend and kink effects from the cis-double bond(s) in the
      hydrocarbon chain affected the membrane fluidity and molecular packing in the
      monolayers, which resulted in a greater interaction between unsaturated C18 fatty
      acids and DP. The most thermodynamically stable mole composition of unsaturated
      C18 fatty acids to DP was observed at 50:1; this ratio is suggested to be the
      best mole ratio and will be subsequently used to prepare DP-C18 fatty-acid
      nanoliposomes. The presence of cis-double bonds in both hydrocarbon chains of
      DOPE in DP also created an imperfection in the membrane structure of lipid-drug
      delivery systems, which is expected to enhance lipid-based systems for antibody
      conjugation and drug encapsulation.

PMID- 28752255
TI  - The representativeness of direct oral anticoagulant clinical trials to
      hospitalized patients with atrial fibrillation.
AB  - PURPOSE: Trials of the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban
      and apixaban provide the basis for prescribing for the prevention of stroke and
      systemic embolism in atrial fibrillation (AF). The objective of this study was to
      assess the representativeness of the three pivotal DOAC randomized controlled
      trials of dabigatran, rivaroxaban and apixaban for unselected hospitalized
      patients with AF. METHODS: A cross-sectional study was undertaken. All patients
      discharged with AF between 2012 and 2015 from a large public hospital network in
      Melbourne, Australia, were identified. Inclusion and exclusion criteria from the
      DOAC trials were applied. The proportions of hospitalized patients with AF who
      would have been eligible for the dabigatran (RE-LY), rivaroxaban (ROCKET-AF) and
      apixaban (ARISTOTLE) trials were estimated, as was pooled eligibility for all
      three trials. Characteristics of eligible and ineligible patients were compared.
      RESULTS: For the 4734 patients, application of the inclusion and exclusion
      criteria resulted in 60.5, 52.6 and 35.8% eligibility for the trials of apixaban,
      dabigatran and rivaroxaban, respectively. Pooled eligibility across all three
      trials demonstrated that 33.4% of the patients would have been eligible for all
      three trials but 36.7% ineligible for any trial. Ineligible patients who met
      exclusion criteria were older and experienced more comorbidities. CONCLUSIONS:
      The apixaban and dabigatran trials may be the most representative of hospitalized
      patients with AF. The DOAC trial results can readily be extrapolated to, and
      guide prescribing for, at least two thirds of patients discharged from a large
      metropolitan health service in Australia.

PMID- 28752256
TI  - Capecitabine-induced hyperglycemia without hyperlipidemia: a case report.

PMID- 28752257
TI  - What is the Best Revascularization Strategy for Acute Occlusive Arterial
      Mesenteric Ischemia: Systematic Review and Meta-analysis.
AB  - PURPOSE: Acute mesenteric ischemia (AMI) is a life-threatening disease that leads
      to bowel infarction and death. The optimal management of AMI remains
      controversial. The present meta-analysis aimed to estimate the prognostic impact
      of surgical (SG) versus endovascular or hybrid intervention (EV) as the first
      line treatment for acute arterial occlusive mesenteric ischemia and to assess
      whether endovascular strategy was actually effective in reducing bowel resection.
      METHODS: MEDLINE, Scopus and the Cochrane Library databases were searched. There
      have been no randomized controlled trials comparing SG versus EV for the
      treatment of AMI. We undertook this systematic review and meta-analysis according
      to MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines,
      assessing the included study quality with the Newcastle-Ottawa scale. RESULTS:
      Seven studies comparing EV versus SG as first strategy for the treatment of AMI
      were selected for the analyses, reporting of 3020 patients. EV was associated
      with a reduced risk of in-hospital mortality (RR 0.68; 95% CI 0.59-0.79; fixed
      effects analysis; p < 0.0001; I 2 = 4.9%; tau 2 = 0.025). Pooled prevalence of
      mortality was 19% for EV and 34% for SG. EV also showed a benefit impact on risk
      of bowel resection and second-look laparotomy. CONCLUSIONS: The present meta
      analysis outlines that endovascular revascularization strategy seems to offer
      advantages in terms of in-hospital mortality and morbidity in case of arterial
      occlusive AMI. A multidisciplinary team consisting of radiologists,
      interventional radiologists, cardiovascular and general surgeons comes out to be
      essential to tailor the right procedure to the patient and improve the outcomes
      associated with AMI.

PMID- 28752258
TI  - Allogeneic Reduced-Intensity Hematopoietic Stem Cell Transplantation for Chronic
      Granulomatous Disease: a Single-Center Prospective Trial.
AB  - PURPOSE: The purpose of this study was to evaluate engraftment and adverse events
      with a conditioning and prophylactic regimen intended to achieve high rates of
      engraftment with minimal graft-versus-host disease (GVHD) in allogeneic
      transplantation for chronic granulomatous disease in a single center. METHODS:
      Forty patients, 37 male, with chronic granulomatous disease were transplanted.
      Transplant products were matched sibling peripheral blood stem cells (PBSCs) in
      four and matched unrelated donor (MUD) bone marrow in three, and one patient
      received mismatched unrelated PBSCs. Thirty-two patients received MUD PBSCs. All
      patients received a conditioning regimen of busulfan/alemtuzumab (with low-dose
      total body irradiation for MUD recipients) with sirolimus graft-versus-host
      disease prophylaxis. RESULTS: Engraftment occured in 38/40 recipients (95%).
      Acute or chronic GVHD occurred in 18 (45%) and 5 (12.5%), respectively, with 6
      episodes of grades III-IV and/or steroid refractory GVHD. Overall survival was
      33/40 (82.5%) and event-free survival was 30/40 (80%). Successful engraftment was
      associated with myeloid and NK cell, but not CD3+ chimerism. Myeloid engraftment
      was greater than 70% in 30/32 recipients at mean follow-up of 3.4 years. Evidence
      of persistent immunodeficiency was not seen in successful transplants. Attempts
      to rescue failed or poorly functioning grafts were associated with unacceptable
      morbidity and mortality. CONCLUSIONS: A reduced-intensity allogeneic transplant
      protocol based on alemtuzumab and busulfan with sirolimus GVHD prophylaxis
      produced high rates of successful engraftment and minimal regimen-related
      toxicity. Prolonged clinical follow-up has confirmed its efficacy in ameliorating
      CGD-related disease. Outcomes were not acceptable with donor cell infusion rescue
      of cause with poor graft function.

PMID- 28752259
TI  - The association of experience of violence and somatization, depression, and
      alexithymia: a sample of women with medically unexplained symptoms in Turkey.
AB  - The aim of the study was to examine the relationship between the levels of
      somatization, depression as well as alexithymia, and MUS in women going through
      violence experience in three contexts (childhood, adulthood, and both childhood
      and adulthood). The study was performed on 180 patients attending the Internal
      Medicine Department of Istanbul University Medical Faculty. The data of women
      with MUS (n = 50) were compared those of women with acute physical conditions (n
      = 46) and chronic physical conditions (n = 84). Semi-structured Interview Form,
      Childhood Abuse and Neglect Inventory, Brief Symptom Inventory, Beck Depression
      Inventory, and the Toronto Alexithymia Scale were administered. The levels of
      somatization and depression were found to be higher in women who were exposed to
      emotional abuse (EA) and physical abuse (PA) in adulthood in the MUS group
      compared with those of the women exposed to EA and PA in adulthood in the other
      groups. The levels of somatization, depression, and alexithymia in the MUS group
      exposed to childhood emotional abuse (CEA) were also higher than those in the
      controls exposed to CEA. The levels of somatization and alexithymia in the MUS
      group who were exposed to childhood physical abuse (CPA) were higher than those
      in the controls exposed to CPA. The levels of somatization and depression in the
      MUS group who were exposed to violence both in childhood and in adulthood were
      higher than those in the controls who experienced violence both in childhood and
      in adulthood. Most women exposed to domestic violence present to health care
      institutions with various physical and psychological symptoms in Turkey. So, it
      is important that health caregivers also ask questions about experiences of
      violence and psychological symptoms in women presenting with medically
      unexplained symptoms.

PMID- 28752260
TI  - Correlates of early pregnancy serum brain-derived neurotrophic factor in a
      Peruvian population.
AB  - Knowledge about factors that influence serum brain-derived neurotrophic factor
      (BDNF) concentrations during early pregnancy is lacking. The aim of the study is
      to examine the correlates of early pregnancy serum BDNF concentrations. A total
      of 982 women attending prenatal care clinics in Lima, Peru, were recruited in
      early pregnancy. Pearson's correlation coefficient was calculated to evaluate the
      relation between BDNF concentrations and continuous covariates. Analysis of
      variance and generalized linear models were used to compare the unadjusted and
      adjusted BDNF concentrations according to categorical variables. Multivariable
      linear regression models were applied to determine the factors that influence
      early pregnancy serum BDNF concentrations. In bivariate analysis, early pregnancy
      serum BDNF concentrations were positively associated with maternal age (r = 0.16,
      P < 0.001) and early pregnancy body mass index (BMI) (r = 0.17, P < 0.001), but
      inversely correlated with gestational age at sample collection (r = -0.21, P <
      0.001) and C-reactive protein (CRP) concentrations (r = -0.07, P < 0.05). In the
      multivariable linear regression model, maternal age (beta = 0.11, P = 0.001),
      early pregnancy BMI (beta = 1.58, P < 0.001), gestational age at blood collection
      (beta = -0.33, P < 0.001), and serum CRP concentrations (beta = -0.57, P = 0.002)
      were significantly associated with early pregnancy serum BDNF concentrations.
      Participants with moderate antepartum depressive symptoms (Patient Health
      Questionnaire-9 (PHQ-9) score >= 10) had lower serum BDNF concentrations compared
      with participants with no/mild antepartum depressive symptoms (PHQ-9 score < 10).
      Maternal age, early pregnancy BMI, gestational age, and the presence of moderate
      antepartum depressive symptoms were statistically significantly associated with
      early pregnancy serum BDNF concentrations in low-income Peruvian women.
      Biological changes of CRP during pregnancy may affect serum BDNF concentrations.

PMID- 28752261
TI  - Leishmanicidal effect of antiparasitic photodynamic therapy-ApPDT on infected
      macrophages.
AB  - The aim of this study is to evaluate the effects of ApPDT (antiparasitic
      photodynamic therapy) on the interaction of Leishmania braziliensis with J774
      macrophages, used as a photosensitizer, methylene blue associated with red laser.
      The tests are in triplicate and the samples divided into four groups: control,
      photosensitizer, laser, and ApPDT. The photosensitizer used was the methylene
      blue at concentration of 12.5 MUg/mL. The parameters of the laser were lambda =
      660 nm, 40 mW, and 8.4 J/cm2. Samples are analyzed by optical microscopy through
      the identification and counting of infected and uninfected macrophages, parasite
      load, infectivity, and infection index. Statistical analysis used ANOVA test with
      Tukey post-test, being considered statistically significant p < 0.05. The
      analysis of the interaction tests shows that the infection rate in the ApPDT
      group in relation to the control group presents a statistically significant
      reduction (p < 0.0001) of 71% at both 24 and 48 h (p < 0.0001) of 62%. ApPDT
      reduces the number of macrophages infected by Leishmania braziliensis, as well as
      the number of intracellular parasites, being a possible alternative therapy in
      the treatment of cutaneous leishmaniosis.

PMID- 28752262
TI  - Discrimination model applied to urinalysis of patients with diabetes and
      hypertension aiming at diagnosis of chronic kidney disease by Raman spectroscopy.
AB  - Higher blood pressure level and poor glycemic control in diabetic patients are
      considered progression factors that cause faster decline in kidney functions
      leading to kidney damage. The present study aimed to develop a quantification
      model of biomarkers creatinine, urea, and glucose by means of selected peaks of
      these compounds, measured by Raman spectroscopy, and to estimate the
      concentration of these analytes in the urine of normal subjects (G_N), diabetic
      patients with hypertension (G_WOL) patients with chronic renal failure doing
      dialysis (G_D). Raman peak intensities at 680 cm-1 (creatinine), 1004 cm-1
      (urea), and 1128 cm-1 (glucose) from normal, diabetic, and hypertensive and doing
      dialysis patients, obtained with a dispersive 830 nm Raman spectrometer, were
      estimated through Origin software. Spectra of creatinine, urea, and glucose
      diluted in water were also obtained, and the same peaks were evaluated. A
      discrimination model based on Mahalanobis distance was developed. It was possible
      to determine the concentration of creatinine, urea, and glucose by means of the
      Raman peaks of the selected biomarkers in the urine of the groups G_N, G_WOL, and
      G_D (r = 0.9). It was shown that the groups G_WOL and G_D had lower creatinine
      and urea concentrations than the group G_N (p < 0.05). The classification model
      based on Mahalanobis distance applied to the concentrations of creatinine, urea,
      and glucose presented a correct classification of 89% for G_N, 86% for G_WOL, and
      79% for G_D. It was possible to obtain quantitative information regarding
      important biomarkers in urine for the assessment of renal impairment in patients
      with diabetes and hypertension, and this information can be correlated with
      clinical criteria for the diagnosis of chronic kidney disease.

PMID- 28752263
TI  - Photobiomodulation therapy by NIR laser in persistent pain: an analytical study
      in the rat.
AB  - Over the past three decades, physicians have used laser sources for the
      management of different pain conditions obtaining controversial results that call
      for further investigations. In order to evaluate the pain relieving possibilities
      of photobiomodulation therapy (PBMT), we tested two near infrared (NIR) laser
      systems, with different power, against various kinds of persistent hyperalgesia
      animal models. In rats, articular pain was reproduced by the intra-articular
      injection of sodium monoiodoacetate (MIA) and complete Freund's adjuvant (CFA),
      while compressive neuropathy was modelled by the chronic constriction injury of
      the sciatic nerve (CCI). In MIA and CFA models, (NIR) laser (MLS-Mphi, ASA
      S.r.l., Vicenza, Italy) application was started 14 days after injury and was
      performed once a day for a total of 13 applications. In MIA-treated animals, the
      anti-hyperalgesic effect of laser began 5 min after treatment and vanished after
      60 min. The subsequent applications evoked similar effects. In CFA-treated rats,
      laser efficacy started 5 min after treatment and disappeared after 180 min. In
      rats that underwent CCI, two treatment protocols with similar fluence but
      different power output were tested using a new experimental device called
      Multiwave Locked System laser (MLS-HPP). Treatments began 7 days after injury and
      were performed during 3 weeks for a total of 10 applications. Both protocols
      reduced mechanical hyperalgesia and hindlimb weight bearing alterations until 60
      min after treatment with a higher efficacy recorded for the animals treated using
      the higher power output. In conclusion, this study supports laser therapy as a
      potential treatment for immediate relief of chronic articular or neuropathic
      pain.

PMID- 28752264
TI  - Papain-like cysteine protease encoding genes in rubber (Hevea brasiliensis):
      comparative genomics, phylogenetic, and transcriptional profiling analysis.
AB  - MAIN CONCLUSION: 43 HbPLCPs representing nine subfamilies or 20 orthologous
      groups were found in rubber, where paralogs were resulted from the recent WGD and
      local duplication. Several senescence-associated genes were also identified.
      Papain-like cysteine proteases (PLCPs) comprise a large family of proteolytic
      enzymes involved in plant growth and development, seed germination, organ
      senescence, immunity, and stress response. Despite their importance and the
      extensive research in the model plant Arabidopsis thaliana, little information is
      available on rubber tree (Hevea brasiliensis), a rubber-producing plant of the
      Euphorbiaceae family. This study performed a genome-wide identification of PLCP
      family genes in rubber, resulting in a relatively high number of 43 members. The
      phylogenetic analysis assigned these genes into nine subfamilies, i.e., RD21 (6),
      CEP (4), XCP (4), XBCP3 (2), THI (1), SAG12 (18), RD19 (4), ALP (2), and CTB (2).
      Most of them were shown to have orthologs in Arabidopsis; however, several
      members in SAG12, CEP and XBCP3 subfamilies form new groups as observed in other
      core eudicots such as Manihot esculenta, Ricinus communis, Populus trichocarpa,
      and Vitis vinifera. Based on an expert sequence comparison, 20 orthologous groups
      (OGs) were proposed for core eudicots, and rubber paralogs were shown to be
      resulted from the recent whole-genome duplication (WGD) as well as local
      duplication. Transcriptional profiling showed distinct expression pattern of
      different members across various tissues, e.g., root, leaf, bark, laticifer,
      flower, and seed. By using the senescence-specific HbSAG12H1 as the indicator,
      the transcriptome of senescent rubber leaves was deeply sequenced and several
      senescence-associated PLCP genes were identified. Results obtained from this
      study provide valuable information for future functional analysis and utilization
      of PLCP genes in Hevea and other species.

PMID- 28752265
TI  - The augmented lipid productivity in an emerging oleaginous model alga Coccomyxa
      subellipsoidea by nitrogen manipulation strategy.
AB  - The lipid productivity controlled by both of biomass and lipid content was really
      crucial for economic-feasibility of microalgae-based biofuels production. This
      study attempted at augmenting lipid productivity in an emerging oleaginous model
      alga Coccomyxa subellipsoidea by different nitrogen manipulation including one
      stage continuous N-sufficiency (OCNS), N-deprivation (OCND), N-limitation (OCNL),
      and also two-stage batch N-starvation (TBNS). Amongst four tested nitrogen
      manipulation strategies, OCNS performed remarkable promoting effect on cell
      metabolic growth and the maximum biomass was achieved by 7.39 g/L. Whereas TBNS
      regime induced the highest lipid content (over 50.5%). Only OCNL treatment
      augmented the lipid productivity by 232.37 mg/L/day, representing 1.25-fold more
      than TBNS and even as much as 5.06-fold more than that of OCND strategy. OCNL
      also strengthened the proportions of saturated (C16:0 and C18:0) and
      monounsaturated fatty acid (C18:1) which were inclined to high-quality biofuels
      making. This might be due to that most part of energy and metabolic flux (e.g.
      acetyl-CoA) derived from TCA cycle and glycolysis flowed into fatty acids
      biosynthesis pathway (especially C18:1) response to OCNL manipulation. This study
      represented a pioneering work of utilizing OCNL for lipids production by C.
      subellipsoidea and clearly implied that OCNL might be a feasible way for algal
      lipid production on a commercial scale and also promoted the potential of C.
      subellipsoidea as an ideal biodiesel feedstock.

PMID- 28752266
TI  - Accuracy of a Laryngopharyngeal Endoscopic Esthesiometer (LPEER) for Evaluating
      Laryngopharyngeal Mechanosensitivity: A Validation Study in a Prospectively
      Recruited Cohort of Patients.
AB  - Recent studies have shown an association between alterations in laryngopharyngeal
      mechanosensitivity (LPMS) and dysphagia, obstructive sleep apnea, and chronic
      cough hypersensitivity syndrome. A previous reliability study of a new
      laryngopharyngeal endoscopic esthesiometer and rangefinder (LPEER) showed high
      intra- and inter-rater reliability; however, its accuracy has not been tested. We
      performed an accuracy study of the LPEER in a prospectively and consecutively
      recruited cohort of 118 patients at two tertiary care university hospitals. Most
      of the patients were suffering from dysphagia, and all of them underwent a
      standard clinical evaluation and fiberoptic endoscopic evaluation of swallowing
      with sensory testing (FEESST) using a new sensory testing protocol. The sensory
      test included determinations of the laryngeal adductor reflex threshold (LART),
      the cough reflex threshold (CRT) and the gag reflex threshold (GRT).
      Abnormalities on these reflex thresholds were evaluated for associations with
      major alterations in swallowing safety (pharyngeal residues, penetration, and
      aspiration). We evaluated the discriminative capacity of the LPMS test using ROC
      curves and the area under the curve (AUC-ROC) and its relationship with the eight
      point penetration-aspiration scale (PAS) using the Spearman's rho correlation
      coefficient (SCC). We found a positive correlation between the PAS and LART (SCC
      0.47; P < 0.001), CRT (SCC 0.46; P < 0.001) and GRT (SCC 0.34; P = 0.002). The
      AUC-ROC values for detecting a PAS >=7 were as follows: LART, 0.83 (P < 0.0001);
      CRT, 0.79 (P < 0.0001); GRT, 0.72 (P < 0.0001). In this study, the LPEER showed
      good accuracy for evaluating LPMS. These results justify further validation
      studies in independent populations.

PMID- 28752267
TI  - Gender Specific Characteristics of Revolving Door Adolescents in Acute
      Psychiatric Inpatient Care.
AB  - This study examined the impact of clinical and family related factors on
      adolescent revolving door (RD) phenomenon, defined as having three or more
      psychiatric hospitalizations before the age of 18. A clinical sample of
      adolescents (N = 508) aged 13-17 years, admitted to psychiatric inpatient care
      between April 2001 through March 2006, were interviewed using the k-SADS-PL and
      the EuropASI instruments. The national Finnish Care Register for Health Care
      provided life-time data on child and adolescent psychiatric inpatient
      hospitalizations. RD boys were shown to be significantly more likely than non-RD
      boys to be admitted to psychiatric inpatient care from child welfare placements
      and have previous self-mutilative behavior (SMB) and suicide attempts. RD girls
      were more likely to come from child welfare placements, have unemployed mothers
      and a history of SMB. Mortality in RD boys was significantly higher compared to
      non-RD boys. Frequent use of psychiatric inpatient care warrants comprehensive
      assessment of suicidal behavior in adolescents.

PMID- 28752268
TI  - Erratum to: A new hereditary colorectal cancer network in the Middle East and
      eastern Mediterranean countries to improve care for high-risk families.

PMID- 28752269
TI  - Opportunities for Skin Cancer Prevention Education among Individuals Attending a
      Community Skin Cancer Screening in a High-Risk Catchment Area.
AB  - Despite the highly preventable nature of skin cancer, it remains the most
      commonly diagnosed form of cancer in the United States. Recommendations for a
      complete skin cancer prevention regimen include engaging in photoprotection
      (e.g., sunscreen use), avoiding skin cancer risk behaviors (e.g., tanning), and
      receiving total body skin exams from a health care provider. The current study
      examined reported engagement in these behaviors among participants attending a
      community skin cancer screening (N = 319) in a high-risk catchment area to assess
      the need for increased health education on skin cancer prevention. Participants'
      responses indicate a history of suboptimal avoidance of skin cancer risk
      behaviors. Over half of participants (52%) reported four or more blistering
      sunburns before age 20, and 46% reported indoor tanning at least one during their
      lifetime. There is a need among this population for education regarding a
      complete skin cancer prevention regimen, which could improve adherence to
      photoprotection and avoidance of skin cancer risk behaviors, thereby reducing
      morbidity and mortality due to skin cancer.

PMID- 28752270
TI  - Combination treatment with dendrosomal nanocurcumin and doxorubicin improves
      anticancer effects on breast cancer cells through modulating CXCR4/NF-kappaB/Smo
      regulatory network.
AB  - Despite advantageous antitumor properties of doxorubicin, the considerable
      cytotoxicity of this chemotherapeutic agent has made it necessary to develop
      combination treatment strategies. The aim of the current study was to investigate
      the possible synergism between dendrosomal nanocurcumin (DNC) and doxorubicin in
      eliciting anticancer effects on MDA-MB-231 metastatic breast cancer cells. The
      expression levels of CXCL12/CXCR4 axis and Hedgehog pathway genes were evaluated
      in patient-derived breast carcinoma tissues by qRT-PCR. MTT assay, Annexin V-FITC
      staining followed by flowcytomety and wound healing assay were used to measure
      the effects caused by DNC and doxorubicin, alone and in combination, on the
      viability, apoptosis induction, and migration of MDA-MB-231 cells, respectively.
      Also, qRT-PCR was exploited to analyze the expression of Smo, NF-kappaB and CXCR4
      in cancer cells. Our results revealed that combination treatment with DNC and
      doxorubicin leads to significantly decreased viability, increased apoptosis, and
      reduced migration of breast cancer cells compared with using each drug alone.
      Also, combination treatment is more efficient that single treatment in reducing
      the expression levels of NF-kappaB and Smo transcripts. Our findings provide
      convincing support for the notion that DNC could synergistically enhance the
      anticancer effects of doxorubicin on metastatic breast cancer cells by improving
      its anti-proliferative, pro-apoptotic, and anti-migratory activities. This may be
      mediated, in part, by downregulating CXCR4, NF-kappaB, and Smo genes. Overall,
      the findings of the current study suggest that DNC might be used as a synergistic
      agent for enhancing therapeutic efficiency and reducing toxic effects of
      doxorubicin on breast cancer cells.

PMID- 28752271
TI  - Psychometric Assessment of the Child Surgery Worries Questionnaire Among
      Portuguese Children.
AB  - Worries are common in surgical patients, especially in children. The present
      study analyzed the factor structure and the psychometric properties of a
      Portuguese version of the Child Surgery Worries Questionnaire (CSWQ-P) in a
      Portuguese sample of 490 children. Exploratory factor analysis, conducted via
      principal axis factoring with oblimin rotation, provided evidence for a four
      factor structure of the 21 item questionnaire. A confirmatory factor analysis was
      also conducted, showing the good fit of this solution. The CSWQ-P proved to have
      one more subscale than the original Spanish version CSWQ. Correlations with the
      children's trait anxiety provided evidence of convergent validity for the CSWQ-P.
      Females also scored higher on worries than males on all subscales. Psychometric
      properties of this revised version of the CSWQ provided support for use with
      young children, and indicate the CSWQ-P has value for use in healthcare practice
      and in clinical research.

PMID- 28752273
TI  - The Association Between Preconception Care Receipt and the Timeliness and
      Adequacy of Prenatal Care: An Examination of Multistate Data from Pregnancy Risk
      Assessment Monitoring System (PRAMS) 2009-2011.
AB  - Objectives Prenatal care (PNC) is a critical preventive health service for
      pregnant women and infants. While timely PNC has been associated with improved
      birth outcomes, improvements have slowed since the late 1990s. Therefore, focus
      has shifted to interventions prior to pregnancy. Preconception care is
      recommended for all women of reproductive age. This study aimed to examine
      preconception care and its association with timeliness and adequacy of PNC.
      Methods This retrospective cohort study used data from a large sample of United
      States first-time mothers (n = 13,509) who participated in the 2009-2011
      Pregnancy Risk Assessment Monitoring System in ten states. Timeliness and
      adequacy of PNC data came from birth certificates, while preconception care
      receipt was self-reported. Logistic regression provided odds ratios (ORs) and 95%
      confidence intervals (CIs) to model the association between preconception care
      receipt and the two PNC outcomes. Results After adjustment, women who received
      preconception care had statistically significant increased odds of timely (OR
      1.30, 95% CI 1.08, 1.57), but not adequate PNC (OR 1.08, 95% CI 0.94, 1.24) as
      compared to women who did not receive preconception care. Pregnancy intention
      modified these associations. Associations were strongest among women with
      intended pregnancies (timely PNC: OR 1.63 and adequate PNC: OR 1.22). Conclusions
      for Practice Given that untimely PNC is associated with adverse birth outcomes,
      the observed association warrants increased focus on implementing preconception
      care. Future studies should investigate how specific components of preconception
      care are associated with PNC timeliness/adequacy, health behaviors during
      pregnancy, and birth outcomes.

PMID- 28752272
TI  - Cadmium and Lead Content in Chosen Commercial Fishery Products Consumed in Poland
      and Risk Estimations on Fish Consumption.
AB  - The presented studies aimed to verify whether fish and fishery products available
      on the Polish market were safe for consumers in terms of Cd and Pb content.
      Safety was evaluated according to the content of Cd and Pb in fishery products
      and based on the share of such products in supplying Cd and Pb in the weekly diet
      of an adult. Fish samples, of which 139 were smoked fish (26 samples of mackerel,
      21 of salmon, 35 of sprat, 38 of eel and 19 of trout) and 117 samples of prepared
      fish-based dishes (20 of salads, 41 of spreads and 56 of marinated herring) were
      analysed. The content of Cd and Pb was determined using the GF AAS method. The
      content of Cd per 1 kg of the analysed product can be represented as follows:
      salads > smoked eel > smoked salmon and mackerel > smoked trout and spreads >
      marinated herring > smoked sprat. The content of Pb per 1 kg of the analysed
      product can be represented as follows: smoked salmon and salads > smoked mackerel
      and spreads > smoked eel > smoked sprat and smoked trout. Most Cd was found in
      salads (on average 10.7 MUg kg-1; range 6.53-14.7 MUg), whereas most Pb was
      recorded in salads (on average 56.8 MUg per kg; range 32.6-78.9 MUg) and
      marinated fish (on average 58.8 MUg per kg; range 19.8-79.6 MUg). Fish and
      fishery products available in Poland are safe for consumers.

PMID- 28752274
TI  - Renal Artery Stenosis: New Findings from the CORAL Trial.
AB  - PURPOSE OF REVIEW: The goal of this review is to summarize recent advances in the
      field and highlight important new insights from the Cardiovascular Outcomes in
      Renal Atherosclerotic Lesions (CORAL) trial regarding the optimal management of
      patients with renal artery stenosis (RAS). RECENT FINDINGS: The CORAL trial
      demonstrated that subjects with RAS had similar outcomes whether randomized to
      optimal medical therapy alone or optimal medical therapy plus renal artery
      stenting. Subgroup analyses have failed to demonstrate that baseline blood
      pressure or lesion gradients can predict which subjects may have improved
      response after stent intervention. Importantly, urine albumin to creatinine ratio
      appears to different subjects that may benefit from stent intervention versus
      subjects that are unlikely to achieve any benefit. In addition, there was a trend
      toward increase benefit in subjects with greater percent stenosis.
      Atherosclerotic RAS is a frequent finding and is often seen in patients with
      resistant hypertension, congestive heart failure, chronic kidney disease, and
      rarely those who need renal replacement therapy. Risk factors for RAS overlap
      with those of generalized atherosclerosis including hyperlipidemia, smoking,
      hypertension, and diabetes. Patients with CAD or PVD frequently have co-existing
      RAS. The management of RAS has been controversial for many years. The CORAL trial
      provides important insights into the optimal management of subjects with RAS.

PMID- 28752275
TI  - The Impact of Antihypertensive Medications on Bone Mineral Density and Fracture
      Risk.
AB  - PURPOSE OF REVIEW: This review summarizes the impact of thiazide diuretics on
      fracture risk in older hypertensive individuals. RECENT FINDINGS: We performed a
      post hoc evaluation of the Antihypertensive and Lipid-Lowering Treatment to
      Prevent Heart Attack Trial, a randomized, prospective, double blind hypertension
      study comparing a thiazide-like diuretic, a calcium channel blocker (CCB), and an
      angiotensin converting enzyme inhibitor (ACEi). We examined the risk of hip and
      pelvic fractures during the in-trial period (n = 22,180 participants; mean 4.9
      year follow-up) and during the post-trial period using national data bases (n =
      16,622 participants) (mean total follow-up 7.8 years). During the trial,
      participants randomized to the thiazide diuretic versus the CCB or the ACEi had a
      lower risk of fracture on adjusted analyses (HR 0.79 [95% CI, 0.63, 0.98], p =
      0.04). Risk of fracture was significantly lower in participants randomized to the
      diuretic as compared to those randomized to the ACEi (HR 0.75 [95% CI, 0.58,
      0.98]; p = 0.04), but not significantly different compared to the CCB (HR 0.87
      [95% CI, 0.71, 1.09]; p = 0.17). Over the entire trial and post-trial period of
      follow-up, the cumulative incidence of fractures was non-significantly lower in
      participants assigned to the diuretic vs assignment to the ACEi or the CCB (HR
      0.87 [0.74-1.03], p = 0.10) and versus each medication separately. These findings
      establish a benefit for thiazide diuretic treatment for the prevention of
      fractures versus other commonly used antihypertensive medications using
      prospective, randomized data. The effects of the thiazide diuretic on bone appear
      to be long lasting.

PMID- 28752276
TI  - Nutrition Education for Cardiologists: The Time Has Come.
AB  - PURPOSE OF REVIEW: Nutrition is a cornerstone of cardiovascular health, yet the
      training of cardiovascular specialists in nutrition has been called into
      question. This report summarizes the current state of nutrition education in the
      training of cardiovascular specialists and offers recommendations for curricular
      enhancements. RECENT FINDINGS: Medical students receive an average of fewer than
      20 h of nutrition education, largely confined to basic sciences and discussion of
      vitamin deficiency states. Current guidelines for Internal Medicine residency and
      cardiovascular fellowship training do not contain any specific requirement for
      nutrition education. A recent survey showed that the vast majority of
      cardiologists report having received minimal nutrition training, although most
      cardiologists believe it is their personal responsibility to provide nutritional
      counseling to their patients. Cardiologists typically receive minimal training in
      nutrition and are not well equipped to deliver effective nutritional counseling
      and recognize opportunities for appropriate referral. The potential for
      cardiologists to become more effective team members in delivering nutritional
      interventions is considerable.

PMID- 28752277
TI  - Myocardial Tissue Engineering for Regenerative Applications.
AB  - PURPOSE OF REVIEW: This review provides an overview of the current state of
      tissue-engineered heart repair with a special focus on the anticipated modes of
      action of tissue-engineered therapy candidates and particular implications as to
      transplant immunology. RECENT FINDINGS: Myocardial tissue engineering
      technologies have made tremendous advances in recent years. Numerous different
      strategies are under investigation and have reached different stages on their way
      to clinical translation. Studies in animal models demonstrated that heart repair
      requires either remuscularization by delivery of bona fide cardiomyocytes or
      paracrine support for the activation of endogenous repair mechanisms. Tissue
      engineering approaches result in enhanced cardiomyocyte retention and sustained
      remuscularization, but may also be explored for targeted paracrine or mechanical
      support. Some of the more advanced tissue engineering approaches are already
      tested clinically; others are at late stages of pre-clinical development. Process
      optimization towards cGMP compatibility and clinical scalability of contractile
      engineered human myocardium is an essential step towards clinical translation.
      Long-term allograft retention can be achieved under immune suppression. HLA
      matching may be an option to enhance graft retention and reduce the need for
      comprehensive immune suppression. Tissue-engineered heart repair is entering the
      clinical stage of the translational pipeline. Like in any effective therapy, side
      effects must be anticipated and carefully controlled. Allograft implantation
      under immune suppression is the most likely clinical scenario. Strategies to
      overcome transplant rejection are evolving and may further boost the clinical
      acceptance of tissue-engineered heart repair.

PMID- 28752278
TI  - Predictors and Therapy of Cardiomyopathy Caused by Frequent Ventricular Ectopy.
AB  - PURPOSE OF REVIEW: The aim of this review is to describe predictors and
      therapeutic principles for PVC-induced cardiomyopathy. RECENT FINDINGS: PVC
      induced cardiomyopathy is a treatable condition resulting in a reversible form of
      cardiomyopathy. PVC-induced cardiomyopathy has only recently been recognized as
      an entity that causes a reversible form of cardiomyopathy. The mechanism of
      development of PVC-induced cardiomyopathy has not yet been elucidated, although
      dyssynchrony appears to play a major role. Multiple factors have been described
      that are independently associated with PVC-induced cardiomyopathy. Predictors of
      PVC-induced cardiomyopathy include PVC prevalence, epicardial origin, male
      gender, longer symptom duration and asymptomatic status, presence of interpolated
      PVCs, lack of circadian variability, and a broader PVC-QRS width. In the presence
      of cardiomyopathy, work-up for structural heart disease and its etiology should
      be performed, followed by aggressive attempts at PVC reduction. There is evidence
      that ablation therapy is superior to medical therapy for frequent PVCs, but
      treatment decisions need to be individualized depending on the patients symptoms,
      PVC prevalence, PVC origin, patients comorbidities, and patient preference. The
      potential of sudden cardiac death associated with the presence of structural
      heart disease needs to be recognized, and appropriate risk stratification is
      mandatory.

PMID- 28752279
TI  - Ablative Radiotherapy as a Noninvasive Alternative to Catheter Ablation for
      Cardiac Arrhythmias.
AB  - PURPOSE OF REVIEW: Stereotactic radioablation is a commonly utilized technology
      to noninvasively treat solid tumors with precision and efficacy. Using a robotic
      arm mounted delivery system, multiple low-dose ionizing radiation beams are
      delivered from multiple angles, concentrating ablative energy at the target
      tissue. Recently, this technology has been evaluated for treatment of cardiac
      arrhythmias. This review will present the basic underlying principles, proof-of
      principle studies, and clinical experience with stereotactic arrhythmia
      radioablation. RECENT FINDINGS: Most recently, stereotactic radioablation has
      been used to safely and effectively treat a limited number of patients with
      malignant arrhythmias, including ventricular tachycardia (VT) and atrial
      fibrillation (AF). Treatment protocols, outcomes, ongoing studies, and future
      directions will be discussed. Stereotactic radioablation is a well-established
      technology that has been shown to be a safe and effective therapy for patients
      with drug-refractory cardiac arrhythmias, including VT and AF. Further clinical
      evaluation to define safety and efficacy in larger populations of patients is
      needed.

PMID- 28752281
TI  - Eschar of Scrub Typhus Hidden in Umbilicus.

PMID- 28752280
TI  - Complementary Role of Echocardiography and Cardiac Magnetic Resonance in
      Hypertrophic Cardiomyopathy.
AB  - PURPOSE OF REVIEW: This review discusses the complementary roles of
      echocardiography and cardiac magnetic resonance in the diagnosis and management
      of patients with hypertrophic cardiomyopathy (HCM). RECENT FINDINGS: Imaging
      using novel echocardiographic techniques and cardiac magnetic resonance (CMR)
      imaging in HCM has demonstrated incremental utility in diagnosis and management
      guidance. Application of 3-D imaging has improved assessment of left ventricular
      (LV) mass and volume by echocardiography. Quantification of myocardial mechanics
      has shown promise for clarification of diagnosis, prognosis, and assessment of LV
      dysfunction. CMR permits 3-D tomographic characterization of cardiac structure
      and tissue characterization which has shown utility for assessing the diverse
      phenotypes in HCM and quantification of left ventricular fibrosis, an
      increasingly recognized poor prognostic marker. Non-invasive cardiac imaging
      remains central for the evaluation of HCM patients. An approach integrating
      echocardiography and CMR as complementary modalities allows for improved
      diagnostic and prognostic assessment.

PMID- 28752282
TI  - CLOVE Syndrome.

PMID- 28752283
TI  - Dissociation of binding and learning processes.
AB  - A single encounter of a stimulus together with a response can result in a short
      lived association between the stimulus and the response [sometimes called an
      event file, see Hommel, Musseler, Aschersleben, & Prinz, (2001) Behavioral and
      Brain Sciences, 24, 910-926]. The repetition of stimulus-response pairings
      typically results in longer lasting learning effects indicating stimulus-response
      associations (e.g., Logan & Etherton, (1994) Journal of Experimental Psychology:
      Learning, Memory, and Cognition, 20, 1022-1050]. An important question is whether
      or not what has been described as stimulus-response binding in action control
      research is actually identical with an early stage of incidental learning (e.g.,
      binding might be seen as single-trial learning). Here, we present evidence that
      short-lived binding effects can be distinguished from learning of longer lasting
      stimulus-response associations. In two experiments, participants always responded
      to centrally presented target letters that were flanked by response irrelevant
      distractor letters. Experiment 1 varied whether distractors flanked targets on
      the horizontal or vertical axis. Binding effects were larger for a horizontal
      than for a vertical distractor-target configuration, while stimulus configuration
      did not influence incidental learning of longer lasting stimulus-response
      associations. In Experiment 2, the duration of the interval between response n -
      1 and presentation of display n (500 ms vs. 2000 ms) had opposing influences on
      binding and learning effects. Both experiments indicate that modulating factors
      influence stimulus-response binding and incidental learning effects in different
      ways. We conclude that distinct underlying processes should be assumed for
      binding and incidental learning effects.

PMID- 28752284
TI  - Brightness scaling of periodic tones.
AB  - Brightness is an attribute often used by musicians when describing timbral
      characteristics. It is related to the spectral distribution of energy, as is
      sharpness, studied by Zwicker (Psychoacoustics: Facts and Models, 1990). In the
      current work, subjects adjusted the spectral slope and thus the spectral centroid
      (SC) of one of a pair of sounds to make it twice as bright as the other, so as to
      build a perceptual scale. The ratio of SC required to double brightness is a
      little less than 2 and decreases as the SC of the tones increases. For these
      tones, the ratio of brightness is statistically different from the ratio of
      sharpness calculated from published models.

PMID- 28752286
TI  - Upper Abdominal Activity in Bone Scan.

PMID- 28752285
TI  - HIV Prevention Among Transgender Populations: Knowledge Gaps and Evidence for
      Action.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize the available
      evidence-based HIV prevention interventions tailored for transgender people.
      RECENT FINDINGS: A limited number of evidence-based HIV prevention interventions
      have been tested with transgender populations. Most existing interventions target
      behavior change among transgender women, with only one HIV prevention program
      evaluated for transgender men. Studies addressing biomedical interventions for
      transgender women are ongoing. Few interventions address social and structural
      barriers to HIV prevention, such as stigma, discrimination, and poverty. Evidence
      based multi-level interventions that address the structural, biomedical, and
      behavioral risks for HIV among transgender populations, including transgender
      men, are needed to address disparities in HIV prevalence. Future research should
      address not only pre-exposure prophylaxis uptake and condom use but also
      structural barriers that limit access to these prevention strategies.

PMID- 28752287
TI  - Effects of topiroxostat in hyperuricemic patients with chronic kidney disease.
AB  - BACKGROUND: Hyperuricemia is associated with chronic kidney disease (CKD).
      Although topiroxostat, a novel, non-purine, selective xanthine oxidase inhibitor,
      has a strong effect against hyperuricemia, limited data are available on its
      renoprotective effect against CKD. METHODS: This study was conducted between
      October 2014 and May 2016. Thirty patients (20 male, 10 female) were administered
      40 mg/day of topiroxostat twice daily. All patients were followed for a year. To
      elucidate the effects of topiroxostat, we evaluated the clinically documented
      primary indication of progression, viz. laboratory evidence of kidney function
      decline (reference indicator), uric acid, and hypertension in different patient
      groups, separated according to their baseline uProt levels and baseline eGFR.
      RESULTS: Topiroxostat treatment resulted in significant reduction in SUA (-1.53
      mg/dL), systolic blood pressure (-8.9 mmHg), diastolic blood pressure (-5.0
      mmHg), and urinary protein excretion (-795.5 mg/gCr) compared with baseline
      values. However, serum creatinine and urinary NAG levels, and estimated
      glomerular filtration rate did not change significantly. CONCLUSIONS:
      Topiroxostat reduced SUA levels effectively and may exhibit renoprotective effect
      in hyperuricemic patients with CKD. Further studies are required to clarify
      whether topiroxostat prevents the progression of renal disease and improves the
      prognosis of CKD patients.

PMID- 28752288
TI  - Application of next-generation sequencing technology to diagnosis and treatment
      of focal segmental glomerulosclerosis.
AB  - A broad range of genetic and non-genetic factors can lead to kidney injury that
      manifests as focal segmental glomerulosclerosis (FSGS), which can be classified
      into primary (idiopathic) and secondary forms. Previous genetic approaches to
      familial or sporadic cases of FSGS or steroid-resistant nephrotic syndrome
      identified causal mutations in a subset of genes. Recently, next-generation
      sequencing (NGS) approaches are becoming a part of a standard assessment in
      medical genetics. Current knowledge of the comprehensive genomic information is
      changing the way we think about FSGS and draws attention not only to
      identification of novel causal genes, but also to potential roles for
      combinations of mutations in multiple genes, mutations with complex inheritance,
      and susceptibility genes with variable penetrance carrying relatively minor but
      significant effects. This review provides an update on recent advances in the
      genetic analysis of FSGS and highlights the potential as well as the new
      challenges of NGS for diagnosis and mechanism-based treatment of FSGS.

PMID- 28752289
TI  - Diabetes mellitus as a cause or comorbidity of chronic kidney disease and its
      outcomes: the Gonryo study.
AB  - BACKGROUND: Diabetes mellitus (DM) is a major cause of end-stage kidney disease
      (ESKD). However, the difference in renal outcomes between DM patients with non
      diabetic renal disease (DM and NDRD) and those with diabetic nephropathy (DN) is
      controversial. The aim of the present study was to evaluate the differences among
      patients with DN, DM, and NDRD, and non-DM chronic kidney disease (CKD) in a
      prospective observational study. METHODS: We extracted the data of 2484 patients
      from 11 nephrology care centers and categorized into three groups as described
      above. The primary outcome was ESKD requiring renal replacement therapy. RESULTS:
      During the median follow-up of 4.44 years, 281 patients (11.3%) developed ESKD.
      Renal outcomes of DM and NDRD patients were similar to those of non-DM patients
      (p >= 0.05). At CKD stage G3b, the hazard ratios (95% confidence intervals) of
      ESKD were 7.10 (2.46-20.49) in DN patients and 0.89 (0.19-4.24) in DM and NDRD.
      The annual change in the estimated glomerular filtration rate (eGFR) in DN
      patients was significantly larger than that in other groups at stage G3b (
      9.7%/year). CONCLUSIONS: We found that DN patients have a higher risk for ESKD
      than DM and NDRD or non-DM patients. In particular, GFR rapidly declined in DN at
      stage G3b. DM and NDRD patients can accomplish equally beneficial renal outcomes
      as non-DM CKD, regardless of their similar metabolic profiles as DN. In
      conclusion, we should prudentially consider the risk stratification of DM whether
      cause or comorbidity of CKD.

PMID- 28752290
TI  - Factors Contributing to the Efficacy-Effectiveness Gap in the Case of Orphan
      Drugs for Metabolic Diseases.
AB  - INTRODUCTION: Authorization of orphan medicinal products (OMPs) is often based on
      studies with several methodological shortcomings. Hence, data are difficult to
      interpret and efficacy does not always correspond to real-world effectiveness. We
      investigated to what extent an efficacy-effectiveness gap exists for OMPs for
      metabolic diseases and set out to explore which factors contribute to it.
      METHODS: We included all OMPs for rare metabolic diseases authorized in the EU up
      to 1 January 2016. Efficacy data were obtained from European Public Assessment
      Reports, relative effectiveness data from the Dutch National Healthcare Institute
      website, and real-world effectiveness data from literature and interviews with
      experts and patients. Efficacy and effectiveness were scored as 'no effect',
      'unclear' or 'good' based upon a prespecified scoring system. RESULTS: We
      identified 31 authorized OMPs, of which 21 had post-marketing studies available,
      thus making it possible to score real-world effectiveness. Eight of 21 (38%) OMPs
      had a 'good' real-world effectiveness. The use of a clinical or validated
      surrogate primary endpoint and a representative study population seemed to be
      related to good effectiveness in the real world, as were type of marketing
      authorization, study population and disease prevalence. CONCLUSIONS: This study
      revealed that less than half of the authorized OMPs are effective in the real
      world. Since the type of primary endpoint used in the pivotal study seems to be
      associated with good real-world effectiveness, it is important to agree upon
      study endpoints through early dialogues among relevant stakeholders.

PMID- 28752291
TI  - Composition and abundance of microbiota in the pharynx in patients with laryngeal
      carcinoma and vocal cord polyps.
AB  - The pharynx is an important site of microbiota colonization, but the bacterial
      populations at this site have been relatively unexplored by culture-independent
      approaches. The aim of this study was to characterize the microbiota structure of
      the pharynx. Pyrosequencing of 16S rRNA gene libraries was used to characterize
      the pharyngeal microbiota using swab samples from 68 subjects with laryngeal
      cancer and 28 subjects with vocal cord polyps. Overall, the major phylum was
      Firmicutes, with Streptococcus as the predominant genus in the pharyngeal
      communities. Nine core operational taxonomic units detected from Streptococcus,
      Fusobacterium, Prevotella, Granulicatella, and Veillonella accounted for 21.3% of
      the total sequences detected. However, there was no difference in bacterial
      communities in the pharynx from patients with laryngeal cancer and vocal cord
      polyps. The relative abundance of Firmicutes was inversely correlated with
      Fusobacteria, Proteobacteria, Actinobacteria, and Bacteroidetes. The correlation
      was evident at the genus level, and the relative abundance of Streptococcus was
      inversely associated with Fusobacterium, Leptotrichia, Neisseria, Actinomyces,
      and Prevotella. This study presented a profile for the overall structure of the
      microbiota in pharyngeal swab samples. Inverse correlations were found between
      Streptococcus and other bacterial communities, suggesting that potential
      antagonism may exist among pharyngeal microbiota.

PMID- 28752292
TI  - Effect of amikacin on cell wall glycopeptidolipid synthesis in Mycobacterium
      abscessus.
AB  - Cultivation of the smooth colony Mycobacterium abscessus at the sub-minimum
      inhibitory concentration (MIC) of amikacin changed its growth pattern including
      its colony morphology (smooth to rough) and cell arrangement (dispersed to cord
      formation). In addition, reduced sliding motility and biofilm formation were
      observed. The amount of glycogpetidolipid (GPL) and mRNA expression of key genes
      involved in GPL synthesis were decreased in the amikacin-treated M. abscessus
      strain. An in vitro infection assay revealed that the amikacin-treated smooth M.
      abscessus strain induced more pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL
      6) than that of the smooth strain in murine macrophage cells. These results
      suggest that long-term exposure to a low concentration of amikacin causes a
      physical change in the cell wall which may increase its virulence.

PMID- 28752293
TI  - Development of recombinant Yarrowia lipolytica producing virus-like particles of
      a fish nervous necrosis virus.
AB  - Nervous necrosis virus (NNV) causes viral encephalopathy and retinopathy, a
      devastating disease of many species of cultured marine fish worldwide. In this
      study, we used the dimorphic non-pathogenic yeast Yarrowia lipolytica as a host
      to express the capsid protein of red-spotted grouper nervous necrosis virus
      (RGNNV-CP) and evaluated its potential as a platform for vaccine production. An
      initial attempt was made to express the codon-optimized synthetic genes encoding
      intact and N-terminal truncated forms of RGNNV-CP under the strong constitutive
      TEF1 promoter using autonomously replicating sequence (ARS)-based vectors. The
      full-length recombinant capsid proteins expressed in Y. lipolytica were detected
      not only as monomers and but also as trimers, which is a basic unit for formation
      of NNV virus-like particles (VLPs). Oral immunization of mice with whole
      recombinant Y. lipolytica harboring the ARS-based plasmids was shown to
      efficiently induce the formation of IgG against RGNNV-CP. To increase the number
      of integrated copies of the RGNNV-CP expression cassette, a set of 26S ribosomal
      DNA-based multiple integrative vectors was constructed in combination with a
      series of defective Ylura3 with truncated promoters as selection markers,
      resulting in integrants harboring up to eight copies of the RGNNV-CP cassette.
      Sucrose gradient centrifugation and transmission electron microscopy of this high
      copy integrant were carried out to confirm the expression of RGNNV-CPs as VLPs.
      This is the first report on efficient expression of viral capsid proteins as VLPs
      in Y. lipolytica, demonstrating high potential for the Y. lipolytica expression
      system as a platform for recombinant vaccine production based on VLPs.

PMID- 28752294
TI  - Characterization and phylogenetic analysis of Varicella-zoster virus strains
      isolated from Korean patients.
AB  - Varicella-zoster virus (VZV) is a causative agent of chickenpox in primary
      infection and shingles after its reactivation from latency. Complete or almost
      complete genomic DNA sequences for various VZV strains have been reported.
      Recently, clinical VZV strains were isolated from Korean patients whose genome
      was sequenced using high-throughput sequencing technology. In this study, we
      analyzed single nucleotide polymorphism (SNP) of VZV strains to genetically
      characterize Korean clinical isolates. Phylogenetic analyses revealed that three
      Korean strains, YC01, YC02, and YC03, were linked to clade 2. Comprehensive SNP
      analysis identified 86 sites specific for the 5 VZV clades. VZV strains isolated
      from Korea did not form a phylogenetic cluster. Rather, YC02 and YC03 clustered
      strongly with Chinese strain 84-7 within clade 2, more specifically cluster 2a.
      Signature sequences for the cluster 2a were identified and found to play an
      important role in the separation of cluster 2a strains from other clade 2
      strains, as shown in substitution studies. Further genetic analysis with
      additional strains isolated from Japan, China, and other Asian countries would
      provide a novel insight into the significance of two distinct subclades within
      clade 2.

PMID- 28752295
TI  - NMR-based metabolomics reveals the metabolite profiles of Vibrio parahaemolyticus
      under ferric iron stimulation.
AB  - Vibrio parahaemolyticus is a halophilic bacterium endemic to coastal areas, and
      its pathogenicity has caused widespread seafood poisoning. In our previous
      research, the protein expression of V. parahaemolyticus in Fe3+ medium was
      determined using isobaric tags for relative and absolute quantitation (iTRAQ).
      Here, nuclear magnetic resonance (NMR) was used to detect changes in the V.
      parahaemolyticus metabolome. NMR spectra were obtained using methanol-water
      extracts of intracellular metabolites from V. parahaemolyticus under various
      culture conditions, and 62 metabolites were identified, including serine,
      arginine, alanine, ornithine, tryptophan, glutamine, malate, NAD+, NADP+,
      oxypurinol, xanthosine, dCTP, uracil, thymine, hypoxanthine, and betaine. Among
      these, 21 metabolites were up-regulated after the stimulation of the cells by
      ferric iron, and 9 metabolites were down-regulated. These metabolites are
      involved in amino acid and protein synthesis, energy metabolism, DNA and RNA
      synthesis and osmolality. Based on these results, we conclude that Fe3+
      influences the metabolite profiles of V. parahaemolyticus.

PMID- 28752296
TI  - Pseudaminobacter granuli sp. nov., isolated from granules used in a wastewater
      treatment plant.
AB  - A Gram negative, aerobic, non-motile and rod-shaped bacterial strain designated
      as Gr-2T was isolated from granules used in a wastewater treatment plant in
      Korea, and its taxonomic position was investigated using a polyphasic approach.
      Strain Gr-2T grew at 18-37 degrees C (optimum temperature, 30 degrees C) and a pH
      of 6.0-8.0 (optimum pH, 7.0) on R2A agar medium. Based on 16S rRNA gene
      phylogeny, the novel strain showed a new branch within the genus Pseudaminobacter
      of the family Phyllobacteriaceae, and formed clusters with Pseudaminobacter
      defluvii THI 051T (98.9%) and Pseudaminobacter salicylatoxidans BN12T (98.7%).
      The G+C content of the genomic DNA was 63.6%. The predominant respiratory quinone
      was ubiquinone-10 (Q-10) and the major fatty acids were cyclo-C19:0 omega8c,
      C18:1 omega7c, and iso-C17:0. The overall polar lipid patterns of Gr-2T were
      similar to those determined for the other Pseudaminobacter species. DNA-DNA
      relatedness values between strain Gr-2T and its closest phylogenetically
      neighbors were below 18%. Strain Gr-2T could be differentiated genotypically and
      phenotypically from the recognized species of the genus Pseudaminobacter. The
      isolate therefore represents a novel species, for which the name Pseudaminobacter
      granuli sp. nov. is proposed with the type strain Gr-2T (=KACC 18877T =LMG
      29567T).

PMID- 28752298
TI  - Diversity, Daily Flight Activity and Temporal Occurrence of Necrophagous Diptera
      Associated with Decomposing Carcasses in a Semi-Arid Environment.
AB  - The harsh conditions of the Brazilian seasonally dry tropical forest known as
      Caatinga pose challenges to the insects specialized in the exploitation of
      ephemeral resources. We investigated the diversity and daily flight activity of
      dipterans associated with decomposing rat carcasses in a field experiment
      performed in the semi-arid region of Pernambuco State, Brazil. We also analyzed
      the temporal arrival of adult insects on the carcasses at three stages of
      decomposition: early, intermediate, and advanced. We collected 1173 individuals,
      of which Muscidae had the highest abundance (36.5%), followed by Sarcophagidae
      (28.1%), Calliphoridae (25.2%), and Fanniidae (10.2%). Chrysomya albiceps
      (Wiedemann, 1819) (Calliphoridae), Fannia pusio (Wiedemann, 1830) (Fanniidae),
      Atherigona orientalis (Schiner, 1868), and Musca domestica (Linnaeus, 1758)
      (Muscidae) were the most abundant species. The richness reached its maximum value
      on the second day of decomposition, with 18 species, decreasing to 8 species on
      the last day of decomposition (7 days). The ecological indices of diversity,
      dominance, and evenness varied little among the stages. There was an overlap of
      most species throughout the decomposition, although the overall abundance was
      higher at the intermediate stage for Calliphoridae, Muscidae, and Sarcophagidae.
      In accordance to previous studies, nocturnal flight was rare, as approximately 8%
      of insects were captured at night. Our results expand the knowledge on ecological
      and behavioral aspects of necrophagous flies under inhospitable environments,
      such as the dry season in the Caatinga. The dominance of the invasive species C.
      albiceps reinforced here illustrates its geographical expansion towards the
      countryside of Northeastern Brazil.

PMID- 28752297
TI  - Uliginosibacterium flavum sp. nov. isolated from an artificial lake.
AB  - A Gram-negative, facultative anaerobic, rod-shaped, motile by means of a polar
      flagellum, greenish-yellow-pigmented bacterial strain (designated strain JJ3220T)
      was isolated from an artificial lake in South Korea and characterized using a
      polyphasic approach. The 16S rRNA gene sequence of strain JJ3220T indicated that
      the isolate belongs to the family Rhodocyclaceae, and that it exhibits 96.4%
      similarity to Uliginosibacterium paludis KBP-13T. The major cellular fatty acids
      of the novel strain were C14:0, C16:0, and summed feature 3 (C16:1 omega6c and/or
      C16:1 omega7c). Strain JJ3220T had flexirubin-type pigments. The DNA G+C content
      of the strain was 62.8%. The major respiratory quinone and major polar lipid of
      strain JJ3220T were ubiquinone-8 and phosphatidylethanolamine, respectively.
      Based on the morphological and physiological properties and biochemical evidence
      presented, it can be concluded that strain JJ3220T represents a novel species of
      the genus Uliginosibacterium. The type strain Uliginosibacterium flavum is
      JJ3220T (=KACC 17644T =JCM 19465T).

PMID- 28752299
TI  - Silica microparticles for sustained zero-order release of an anti-CD40L antibody.
AB  - Silica microparticle hydrogel depot (HG) formulation was prepared using spray
      drying of silica-based sol-gels for the sustained delivery of MR1 antibody which
      binds to CD40 ligand (CD40L). The formulation was tested in vitro for antibody
      release, surface morphology, particle size, rheology, and injectability. In vivo
      pharmacokinetic evaluation was performed for the microparticle formulation and
      free MR1 antibody in BALB/c female mice. Serum samples up to day 62 were assessed
      using an enzyme-linked immunosorbent assay. In vitro release indicated that the
      MR1 antibody was uniformly encapsulated in silica microparticles, and less than
      5% burst release of the antibody was observed. In vivo pharmacokinetics showed a
      zero-order release up to 62 days from the MR1 silica microparticle HG-controlled
      release composition.

PMID- 28752300
TI  - Functions of Aggression and Peer Victimization in Elementary School Children: the
      Mediating Role of Social Preference.
AB  - This study examined whether social preference was a mechanism that explained the
      relation between proactive and reactive aggression and peer victimization.
      Participants were 494 children in grades 2-5. Proactive and reactive aggression
      was assessed via a self-report measure and indices of social preference and peer
      victimization were assessed via a peer nomination inventory. Data was collected
      during the fall and spring of two academic years. The relations among aggression,
      social preference, and peer victimization varied as a function of aggression and
      gender. For girls, reactive aggression was a significant negative predictor of
      social preference. Findings also revealed social preference mediated the relation
      between reactive aggression and peer victimization for girls. This pathway did
      not hold for boys. There was some evidence that proactive aggression was
      negatively associated with peer victimization, but only for girls. Findings from
      the current study suggest social preference may be a key mechanism through which
      reactive aggression is associated with future victimization for girls. Boys'
      aggression was not related to subsequent peer victimization. Future research and
      intervention efforts should consider gender differences and the function of
      aggression when investigating children's peer victimization experiences.

PMID- 28752302
TI  - Jusepe de Ribera "Lo Spagnoletto": Sileno ebbro.

PMID- 28752301
TI  - Gender differences in the association of ELMO1 genetic variants with type 2
      diabetes in Tunisian Arabs.
AB  - PURPOSE: Polymorphisms of the engulfment and cell motility 1 (ELMO1) gene were
      recently associated with type 2 diabetes (T2DM) and its complications. We
      investigated the association of rs10255208, rs7782979, and rs2041801 ELMO1 gene
      variants with T2DM in Tunisian Arabs. METHODS: Subjects comprised 900 T2DM
      patients and 600 normoglycemic controls. ELMO1 genotyping was done by PCR-RFLP;
      the contribution of ELMO1 variants to T2DM was analyzed by Haploview and
      regression analysis. RESULTS: Minor allele frequencies of rs7782979 and
      rs10255208 ELMO1 variants were significantly higher among unselected T2DM cases
      than controls, and significant differences in the distribution of rs7782979
      genotypes were seen between T2DM cases and control subjects, which was seen in
      male but not female subjects. Three-locus ELMO1 haplotype analysis identified
      haplotype GAA to be positively associated, and haplotypes GCA, AAA, and GCG to be
      negatively associated with T2DM. The distribution of these haplotypes was gender
      dependent for some (GCA, GCG, AAG), and gender-independent for others (GAA, AAA).
      This translated into altered risk of T2DM in male or female subjects, which
      persisted after adjusting for BMI, systolic and diastolic blood pressure, and
      serum lipid profile. CONCLUSION: These results confirm role for ELMO1 as T2DM
      susceptibility locus, which appears to be gender-dependent.

PMID- 28752303
TI  - Estimation of daily fish intake values for use with water quality criteria for
      human health assessments in Korea.
AB  - Daily fish intake is a key parameter of water quality criteria for protecting
      human health. Daily fish intake values should be representative of consumption
      patterns and must be practical for regulatory purposes. Thus, values must be
      scientifically verified and regularly updated for inclusion in water quality
      criteria. In Korea, four different fish intake values have been identified from
      food balance sheets (KREI 2000), the Korea National Health and Nutrition
      Examination Survey (KNHANES) II (Ministry of Health and Welfare 2002), Korean
      Exposure Factors Handbook (MOE 2007a), and KNHANES IV-V (CDC 2008; 2009; 2010),
      which have been applied to water quality standards and related national projects
      and regulations. This paper reviews the estimation methodologies of previous
      daily fish intake values from multiple sources and improvements in these values
      between 2000 and 2012. Finally, limitations associated with each value were
      examined to assist future research and regulatory management. This review
      provides information on changes in the daily fish intake values and their
      application in water quality standards in Korea.

PMID- 28752304
TI  - UV-C as a means to combat biofilm proliferation on prehistoric paintings:
      evidence from laboratory experiments.
AB  - A laboratory investigation of UV-C effects was conducted over a 62-h period: a
      much higher dose than in classic UV-C treatment was applied to five pigments and
      two painting binders used by prehistoric humans. Colorimetric parameters were
      compared to a control to see if UV-C can change pigment and binder color.
      Infrared spectroscopy, scanning electron microscopy, inductively coupled plasma
      and X-ray crystallography were also carried out to confirm colorimetric
      measurement. In order to understand how microorganism may physically deteriorate
      paintings, limestone blocks were painted and monitored until their complete
      colonization by algae, cyanobacteria, fungi and/or mosses. The results show that
      UV-C has no effect on mineral compounds. Conversely, it is noteworthy that binder
      color changed under both UV-C light conditions as well as in visible light.
      Concerning painted blocks, a fast proliferation has been observed with
      deterioration of the paintings. These results show the high importance of
      treating biofilm as soon as possible. Moreover, these findings may be a promising
      avenue inducing cave managers to use friendly UV-C light to treat contaminated
      cave paintings and also in the prevention of biodeterioration by lampenflora.

PMID- 28752305
TI  - Model and algorithm for bi-fuel vehicle routing problem to reduce GHG emissions.
AB  - Because of the harmful effects of greenhouse gas (GHG) emitted by petroleum-based
      fuels, the adoption of alternative green fuels such as biodiesel and compressed
      natural gas (CNG) is an inevitable trend in the transportation sector. However,
      the transition to alternative fuel vehicle (AFV) fleets is not easy and,
      particularly at the beginning of the transition period, drivers may be forced to
      travel long distances to reach alternative fueling stations (AFSs). In this
      paper, the utilization of bi-fuel vehicles is proposed as an operational
      approach. We present a mathematical model to address vehicle routing problem
      (VRP) with bi-fuel vehicles and show that the utilization of bi-fuel vehicles can
      lead to a significant reduction in GHG emissions. Moreover, a simulated annealing
      algorithm is adopted to solve large instances of this problem. The performance of
      the proposed algorithm is evaluated on some random instances.

PMID- 28752306
TI  - Hexabromocyclododecanes in soils and plants from a plastic waste treatment area
      in North China: occurrence, diastereomer- and enantiomer-specific profiles, and
      metabolization.
AB  - Plastic waste is a source of organic contaminants such as hexabromocyclododecanes
      (HBCDs). HBCDs have been found to cause developmental and reproductive toxicity;
      it is important to investigate the occurrence and metabolization of HBCDs in the
      soil environments with plastic waste contamination. This work analyzed HBCDs and
      their metabolites in soil and plant samples collected from Xinle and Dingzhou-the
      major plastic waste recycling centers in North China. Results showed that total
      HBCD concentrations in soils followed the order: plastic waste treatment site
      (11.0-624 ng/g) > roadside (2.96-85.4 ng/g) >= farmland (8.69-55.5 ng/g). HBCDs
      were detected in all the plant samples with total concentrations ranging from
      3.47 to 23.4 ng/g. gamma-HBCD was the dominant congener in soils, while alpha
      HBCD was preferentially accumulated in plants. Compositions of HBCD isomers in
      soils and plants were significantly different (P < 0.05) among sampling sites and
      among plant species. HBCDs in farmland soil and all plant samples exhibited high
      enantio-selectivity based on the enantiomeric fractions (EFs). Furthermore,
      metabolites of pentabromocyclododecenes (PBCDEs) were frequently identified in
      soils, and mono-OH-HBCDs were the most common ones in plants. This study for the
      first time provides evidences of HBCD contamination in the soil-plant system
      caused by plastic waste, their stereo-selectivity, and metabolization behavior,
      improving our understanding of the environmental behavior and fate of HBCDs.

PMID- 28752307
TI  - Metal uptake capability of Cyperus articulatus L. and its role in mitigating
      heavy metals from contaminated wetlands.
AB  - Wetland plants are biological filters that play an important role in maintaining
      aquatic ecosystem and can take up toxic metals from sediments and water. The
      present study investigated the seasonal variation in the accumulation potential
      of heavy metals by Cyperus articulatus in contaminated watercourses. Forty
      quadrats, distributed equally in 8 sites (six contaminated sites along Ismailia
      canal and two uncontaminated sites along the River Nile), were selected
      seasonally for sediment, water, and plant investigations. Autumn was the
      flourishing season of C. articulatus with the highest shoot density, length, and
      diameter as well as aboveground biomass, while summer showed the least growth
      performance. The photosynthetic pigments were markedly reduced under
      contamination stress. C. articulatus plants accumulated concentrations of most
      heavy metals, except Pb, in their roots higher than the shoots. The plant tissues
      accumulated the highest concentrations of Fe, Cd, Ni, and Zn during autumn, while
      Cu and Mn during spring, and Cr and Co during winter. It was found that Cd, Cu,
      Ni, Zn, Pb, and Co had seasonal bioaccumulation factor (BF) > 1 with the highest
      BF for Cd, Ni, and Zn during autumn, Co, Cu, and Pb in winter, spring, and
      summer, respectively. The translocation factor of most heavy metals, except Pb in
      spring, was <1 indicating potential phytostabilization of these metals. In
      conclusion, autumn is an ideal season for harvesting C. articulatus in order to
      monitor pollution in contaminated wetlands.

PMID- 28752308
TI  - Green synthesis of gold nanoparticles using fungus Mariannaea sp. HJ and their
      catalysis in reduction of 4-nitrophenol.
AB  - In the present study, biosynthesis of gold nanoparticles (AuNPs) by the cells
      (cells-AuNPs) and cell-free extracts (extracts-AuNPs) of a new fungus Mariannaea
      sp. HJ was reported. The as-synthesized particles were characterized by UV-vis
      spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD),
      and Fourier transform infrared spectroscopy (FTIR). The effects of different
      parameters on AuNP biosynthesis were investigated, and initial gold ion
      concentration of 2 mM, pH 7, was demonstrated to be suitable for both cells-AuNP
      and extracts-AuNP syntheses. The cells-AuNPs were of various shapes, including
      sphere, hexagon, and irregular shapes, with an average size of 37.4 nm, while the
      extracts-AuNPs were almost spherical and pseudo-spherical with an average size of
      11.7 nm. XRD pattern suggested that the crystal structure of both AuNPs was face
      centered cubic. FTIR spectra implied that some biomolecules from the fungal cell
      walls or cell-free extracts were involved in the formation of AuNPs. The as
      synthesized AuNPs were demonstrated to have excellent catalytic activities for
      the reduction of 4-nitrophenol with the catalytic rate constants of 5.7 * 10-3/s
      for cells-AuNPs and 24.7 * 10-3/s for extracts-AuNPs. To the best of our
      knowledge, this is the first report on AuNP biosynthesis by Mariannaea sp.

PMID- 28752309
TI  - Cadmium phytoremediation potential of turnip compared with three common high Cd
      accumulating plants.
AB  - Phytoextraction is a phytoremediation technique used for remediating polluted
      soils and it greatly relies on the plants' capacities to accumulate contaminants.
      Turnip is a high cadmium (Cd)-accumulating plant. We compared the Cd tolerance,
      growth, and Cd accumulation characteristics of two turnip landraces with three
      additional commonly known high Cd-accumulating species to systematically estimate
      its Cd phytoremediation potential. Results showed that the turnips could tolerate
      relatively lower Cd concentrations than other plants. Growth characteristics
      analyses indicated that the turnips initially grew rapidly and then gradually
      slowed down, and their photosynthetic parameters indicated that biomass
      accumulation was easily affected by light. However, the Cd uptake and
      translocation capacities of the two turnip landraces were higher than those of
      Phytolacca americana Linn. and Bidens pilosa Linn. but close to that of Brassica
      napus Linn.. Ultimately, large amounts of Cd accumulated in turnips during early
      growth and slightly increased as the fleshy roots increased in size. Based on
      these findings, the present turnip landraces have potential for soil remediation,
      but additional research is needed before these landraces can be practically used.
      Moreover, turnips are good candidates for studying the molecular mechanism of
      high Cd accumulation in plants.

PMID- 28752310
TI  - Impact of metal artifact reduction software on image quality of gemstone spectral
      imaging dual-energy cerebral CT angiography after intracranial aneurysm clipping.
AB  - PURPOSE: We aimed to assess the impact of metal artifact reduction software
      (MARs) on image quality of gemstone spectral imaging (GSI) dual-energy (DE)
      cerebral CT angiography (CTA) after intracranial aneurysm clipping. METHODS: This
      retrospective study was approved by the institutional review board, which waived
      patient written consent. From January 2013 to September 2016, single source DE
      cerebral CTA were performed in 45 patients (mean age: 60 +/- 9 years, male 9)
      after intracranial aneurysm clipping and reconstructed with and without MARs.
      Signal-to-noise (SNR), contrast-to-noise (CNR), and relative CNR (rCNR) ratios
      were calculated from attenuation values measured in the internal carotid artery
      (ICA) and middle cerebral artery (MCA). Volume of clip and artifacts and relative
      clip blurring reduction (rCBR) ratios were also measured at each energy level
      with/without MARs. Variables were compared between GSI and GSI-MARs using the
      paired Wilcoxon signed-rank test. RESULTS: MARs significantly reduced metal
      artifacts at all energy levels but 130 and 140 keV, regardless of clips' location
      and number. The optimal rCBR was obtained at 110 and 80 keV, respectively, on GSI
      and GSI-MARs images, with up to 96% rCNR increase on GSI-MARs images. The best
      compromise between metal artifact reduction and rCNR was obtained at 70-75 and 65
      70 keV for GSI and GSI-MARs images, respectively, with up to 15% rCBR and rCNR
      increase on GSI-MARs images. CONCLUSION: MARs significantly reduces metal
      artifacts on DE cerebral CTA after intracranial aneurysm clipping regardless of
      clips' location and number. It may be used to reduce radiation dose while
      increasing CNR.

PMID- 28752311
TI  - Natural history of lesions with the MR imaging appearance of multinodular and
      vacuolating neuronal tumor.
AB  - PURPOSE: Multinodular and vacuolating neuronal tumor (MVNT) have been recently
      added to the WHO classification of CNS tumors and has not been extensively
      reported upon in the radiological literature. We report the first radiological
      and the largest series of cases, aiming to highlight the natural history of
      lesions with the imaging appearance of MVNT with long follow-up time. METHODS: In
      this retrospective study, we collected cases with the imaging appearance of MVNT.
      All lesions were evaluated by using routine MR imaging, with follow-up of up to
      93 months. Patient demographics, clinical course, and MRI features of the lesions
      were recorded. RESULTS: Twenty-four subjects were enrolled, f/m = 16:8, age range
      24-59 years, with a median age of 45 years. The patients' symptoms were often
      episodic and most frequently due to headaches in 12 (50%), visual symptoms in 6
      (25%), seizures in 5 +/- 1 (20-25%), paresthesia in 4 (~17%), cognitive
      difficulties in 4 (~17%), in addition to other variable neurological symptoms, or
      incidental. A total of 30 lesions identified, 77% of the lesions had gadolinium
      enhanced MRI and only 13% showed enhancement. A 6.7% of the lesions that had MRI
      followed up showed progression, while the rest remained stable up to 93 months
      interval. All patients had intact neurological examinations (except one case that
      was diagnosed with optic neuritis), were managed conservatively, and did well.
      CONCLUSION: The natural history of lesions with imaging features of MVNT is
      overall stable from a clinical and imaging appearance over time.

PMID- 28752312
TI  - Ischemia and inflammation on chronic kidney disease.

PMID- 28752313
TI  - The elusive role of myocardial perfusion imaging in stable ischemic heart
      disease: Is ISCHEMIA the answer?
AB  - The assessment of ischemia through myocardial perfusion imaging (MPI) is widely
      accepted as an index step in the diagnostic evaluation of stable ischemic heart
      disease (SIHD). Numerous observational studies have characterized the prognostic
      significance of ischemia extent and severity. However, the role of ischemia in
      directing downstream SIHD care including coronary revascularization has remained
      elusive as reductions in ischemic burden have not translated to improved clinical
      outcomes in randomized trials. Importantly, selection bias leading to the
      inclusion of many low risk patients with minimal ischemia have narrowed the
      generalizability of prior studies along with other limitations. Accordingly, an
      ongoing randomized controlled trial entitled ISCHEMIA (International Study of
      Comparative Health Effectiveness with Medical and Invasive Approaches) will
      compare an invasive coronary revascularization strategy vs a conservative medical
      therapy approach among stable patients with moderate to severe ischemia. The
      results of ISCHEMIA may have a substantial impact on the management of SIHD and
      better define the role of MPI in current SIHD pathways of care.

PMID- 28752314
TI  - Predictors of recurrent hospital admissions among prostate cancer survivors.
AB  - Cancer survivors often have poor outcomes compared to their peers without cancer.
      Mortality from prostate cancer has been steadily decreasing, and these cancer
      survivors have other comorbidities that progress over time. Current study
      explores the type of admissions and associated risk factors with recurrent
      hospitalizations among prostate cancer survivors. A retrospective review of
      medical records was performed at a single academic institution for male patients
      aged 40 years and older who were diagnosed with prostate cancer more than 2 years
      prior to the study's observation period from January 2008 to December 2010.
      Unpaired t test and Chi-square tests were used to compare patients'
      characteristics, and logistic regression models were used to assess risk factors
      association with recurrent admissions. In total, 245 prostate cancer survivors
      were stratified by single versus recurrent hospital admission. The
      characteristics of the study population were similar to the exception of mean
      Gleason score that was lower, while cardiovascular admissions and clinical
      comorbidities were higher in the recurrent group. In the multivariable regression
      analyses where sociodemographic, primary prostate cancer treatment-related
      sequelae and clinical comorbid conditions were simultaneously analyzed,
      congestive heart failure (OR 3.90, 95% CI 1.25-12.2) and history of metastasis
      (OR 8.10, 95% CI 1.10-60.1) were associated with recurrent hospital admissions.
      Prostate cancer survivors experience a greater number of recurrent admissions,
      and therefore, understanding the nature of these admissions and associated
      medical comorbidities may help us in developing screening or preventive
      strategies to reduce the readmissions for this group of cancer survivors.

PMID- 28752316
TI  - Practical Management of Cardiovascular Comorbidities in Rheumatoid Arthritis.
AB  - Cardiovascular (CV) comorbidities are a frequent extra-articular manifestation of
      rheumatoid arthritis (RA). Cardiovascular disease (CVD) with accelerated
      atherosclerosis is a major cause of morbidity and mortality in patients with RA.
      Subclinical CVD may be present since the early phase of RA. Not only traditional
      but also non-traditional CV risk factors are involved in the pathogenesis of RA
      related CVD. Due to the lack of specifically designed randomized clinical trials,
      it is still unclear which tools to use to perform CV risk assessment, how to
      interpret the results and which interventions are appropriate in RA patients both
      to prevent and to manage CVD. Based on the available evidence, we propose a
      practical approach.

PMID- 28752317
TI  - Shifting the set of stimulus selection when switching between tasks.
AB  - Switching between tasks associated with different requirements of stimulus
      selection may suffer interference from persisting attentional settings or
      processes of reconfiguration, possibly constituting a source of task switch costs
      (i.e., impaired performance in task switch trials compared to task repetition
      trials). To explore the processes involved in task switching with and without a
      switch in stimulus selection requirements, we administered a task-switching
      paradigm that involved task-unique sets of hierarchical (Navon) stimuli,
      preventing stimulus-related proactive interference (i.e., impaired responding to
      a stimulus that was previously processed in the context of a different task), and
      varied, between groups of participants, whether the target stimulus level (i.e.,
      global vs. local) was held constant or varied between the tasks. Mixing target
      levels impaired performance overall and increased the task switch costs.
      Moreover, (within-task) global-local congruency effects were larger when target
      levels were mixed, particularly in task switch trials, suggesting relatively
      stronger stimulus processing according to the attentional set of the other task.
      In a second phase of the experimental session, the target level was changed
      persistently for either one or for both tasks, presumably evoking stimulus
      related proactive interference. This change yielded large task switch costs and
      global-local congruency effects when it resulted in mixed target levels, but not
      when it resulted in a constant target level. These results are consistent with
      the notion that stimulus-related proactive interference is reduced by constant
      withdrawal of attention from the perceptual dimension of the interference
      eliciting stimuli.

PMID- 28752318
TI  - Sex differences in hippocampal damage, cognitive impairment, and trophic factor
      expression in an animal model of an alcohol use disorder.
AB  - Compared to men, women disproportionally experience alcohol-related organ damage,
      including brain damage, and while men remain more likely to drink and to drink
      heavily, there is cause for concern because women are beginning to narrow the
      gender gap in alcohol use disorders. The hippocampus is a brain region that is
      particularly vulnerable to alcohol damage, due to cell loss and decreased
      neurogenesis. In the present study, we examined sex differences in hippocampal
      damage following binge alcohol. Consistent with our prior findings, we found a
      significant binge-induced decrement in dentate gyrus (DG) granule neurons in the
      female DG. However, in the present study, we found no significant decrement in
      granule neurons in the male DG. We show that the decrease in granule neurons in
      females is associated with both spatial navigation impairments and decreased
      expression of trophic support molecules. Finally, we show that post-binge
      exercise is associated with an increase in trophic support and repopulation of
      the granule neuron layer in the female hippocampus. We conclude that sex
      differences in alcohol-induced hippocampal damage are due in part to a paucity of
      trophic support and plasticity-related signaling in females.

PMID- 28752319
TI  - Lower limb muscle activity during gait in individuals with hearing loss.
AB  - The objective of this study was to investigate the electrical activity of lower
      limb muscles during gait in an able-bodied control group and in deaf individuals.
      Thirty male children were equally divided into a control group and a group of
      deaf children. A portable EMG system was used to record the activity of the
      bilateral tibialis anterior, gastrocnemius medialis and vastus lateralis muscles
      during barefoot walking with and without dual task. For EMG analysis, the average
      root mean square (RMS) values of the five trials were calculated and then
      normalized based on the peak RMS obtained by the maximum isometric voluntary
      contraction. MANOVA test was used for between group comparisons. The significance
      level was set at p < 0.05 for all analyses. The findings indicated that gait
      speed in children with hearing loss was smaller than that in control group. Dual
      task resulted in a decreased walking speed of children with hearing loss. The
      activities of tibialis anterior muscle in terminal stance phase (p = 0.040),
      medial gastrocnemius muscle in loading response and initial swing phases (p <
      0.05), and vastus lateralis muscle in the terminal stance and pre swing phases (p
      < 0.05) were greater in deaf group. In deaf children the gait speed was reduced
      and the muscle activity was increased with respect to those in control group.
      This altered gait speed and muscle activity is suggestive of a lower mechanical
      efficiency of gait in deaf children.

PMID- 28752320
TI  - Polymer gel dosimeters with PVA-GA matrix.
AB  - Properties of a new polymer gel with cross-linked polyvinyl alcohol as a
      gelatinous matrix were investigated. The new polymer gel dosimeter was named
      PVABAT. The irradiation was performed using a calibrated 60Co beam. The dose
      responses of the PVABAT formulations were quantified with MRI transverse
      relaxation rate (R2) measurements. The results show that the PVABAT gel responds
      linearly to the absorbed dose for doses from 30 up to 45 Gy. The maximal amount
      of [Formula: see text] of PVABAT polymer gel dosimeter was about 0.19 Gy which
      was indicated on a better resolution in comparison with previously reported
      acrylamide-based polymer gel dosimeters formulations. Furthermore, the gel
      response remains stable in the investigated time (192 h) after the irradiation.
      The effective atomic number and electron density of the new gel showed a maximum
      difference of 3.2 and 2% with soft tissue respectively. The melting point also
      increased significantly for new formulation. Furthermore, the new gel formulation
      has an elemental tissue equivalency for dosimetry applications involving nuclear
      reactions.

PMID- 28752321
TI  - A new scoring system for evaluating coronary artery disease by using blood
      pressure variability.
AB  - The aim of this study was to develop a new scoring system using ambulatory blood
      pressure monitoring (ABPM) to assist in the evaluation of coronary artery disease
      (CAD). One hundred twenty-five subjects (53.1 +/- 9.6 years of age) were
      included. Pearson's tests were first performed to identify the parameters that
      correlated with Duke Treadmill Score (DTS). Blood test parameters and blood
      pressure variability (BPV) measures that were extracted from the ABPM were
      included. Next, a multiple linear regression analysis was performed to train a
      new scoring system in the 84 patients from the 125 patients. Then, a correlation
      analysis was conducted to validate the correlation between the new scoring system
      and DTS in the remaining 41 subjects. A further correlation analysis was used to
      verify the clinical value of the new scoring system using ultrasonic cardiogram
      (UCG) and brachial-ankle pulse wave velocity (baPWV). Our new scoring system,
      which had a 24.096 - 0.083 * residual standard deviation of night systolic blood
      pressure (SBP) - 0.130 * age - 0.206 * average real variability of night SBP, was
      correlated with DTS (r = 0.312, P = 0.047). Moreover, our new scoring system was
      also correlated with various markers of cardiac function (r = -0.290, P = 0.001;
      r = -0.262, P = 0.004; r = -0.303, P = 0.001; r = -0.306, P = 0.001,
      respectively) measured by UCG and with baPWV (r = 0.529, P = 0.001). Furthermore,
      the r-values for the BPV Score versus the markers were closer to -1 than the
      corresponding r-values for the Duke Score vs the same parameters. And the
      differences in r-values between Duke Score and BPV Score were statistically
      significant (P = 0.022). In conclusion, the new scoring system based on ABPM has
      potential as a non-invasive tool for evaluating CAD.

PMID- 28752322
TI  - Redefining the Practice of Peer Review Through Intelligent Automation Part 2:
      Data-Driven Peer Review Selection and Assignment.
AB  - In conventional radiology peer review practice, a small number of exams
      (routinely 5% of the total volume) is randomly selected, which may significantly
      underestimate the true error rate within a given radiology practice. An
      alternative and preferable approach would be to create a data-driven model which
      mathematically quantifies a peer review risk score for each individual exam and
      uses this data to identify high risk exams and readers, and selectively target
      these exams for peer review. An analogous model can also be created to assist in
      the assignment of these peer review cases in keeping with specific priorities of
      the service provider. An additional option to enhance the peer review process
      would be to assign the peer review cases in a truly blinded fashion. In addition
      to eliminating traditional peer review bias, this approach has the potential to
      better define exam-specific standard of care, particularly when multiple readers
      participate in the peer review process.

PMID- 28752323
TI  - Bone Tumor Diagnosis Using a Naive Bayesian Model of Demographic and Radiographic
      Features.
AB  - Because many bone tumors have a variety of appearances and are uncommon, few
      radiologists develop sufficient expertise to guide optimal management. Bayesian
      inference can guide decision-making by computing probabilities of multiple
      diagnoses to generate a differential. We built and validated a naive Bayes
      machine (NBM) that processes 18 demographic and radiographic features. We
      reviewed over 1664 analog radiographic cases of bone tumors and selected 811
      cases (66 diagnoses) for annotation using a quantitative imaging platform. Leave
      one-out cross validation was performed. Primary accuracy was defined as the
      correct pathological diagnosis as the top machine prediction. Differential
      accuracy was defined as whether the correct pathological diagnosis was within the
      top three predictions. For the 29 most common diagnoses (710 cases), primary
      accuracy was 44%, and differential accuracy was 60%. For the top 10 most common
      diagnoses (478 cases), primary accuracy was 62%, and differential accuracy was
      80%. The machine returned relevant diagnoses for the majority of unknown test
      cases and may be a feasible alternative to machine learning approaches such as
      deep neural networks or support vector machines that typically require larger
      training data (our model required a minimum of five samples per diagnosis) and
      are "black boxes" (our model can provide details of probability calculations to
      identify features that most significantly contribute to truth diagnoses).
      Finally, our Bayes model was designed to scale and "learn" from external data,
      enabling incorporation of outside knowledge such as Dahlin's Bone Tumors, a
      reference of anatomic and demographic statistics of more than 10,000 tumors.

PMID- 28752324
TI  - Effect of Glucose on 3D Cardiac Microtissues Derived from Human Induced
      Pluripotent Stem Cells.
AB  - Maternal hyperglycemia is a risk factor for fetal cardiac anomalies. This study
      aimed to assess the effect of high glucose on human induced pluripotent stem cell
      derived cardiomyocyte self-assembly into 3D microtissues and their calcium
      handling. Stem cells were differentiated to beating cardiomyocytes using
      established protocols. On the final day of the differentiation process, cells
      were treated with control media, 12 mM glucose, or 12 mM mannitol (an osmolality
      control). Once beating, the cardiac cells were dissociated with trypsin,
      collected, mixed with collagen, and plated into custom-made silicone micro molds
      in order to generate 3D cardiac microtissues. A time-lapse microscope took
      pictures every 4 h to quantify the kinetics of cellular self-assembly of 3D
      cardiac tissues. Fiber widths were recorded at 4-h intervals and plotted over
      time to assess cardiomyocyte 3D fiber self-assembly. Microtissue calcium flux was
      recorded with optical mapping by pacing microtissues at 0.5 and 1.0 Hz. Exposure
      to high glucose impaired the ability of cardiomyocytes to self-assemble into
      compact microtissues, but not their ability to spontaneously contract. Glucose
      exposed cardiomyocytes took longer to self-assemble and finished as thicker
      fibers. When cardiac microtissues were paced at 0.5 and 1.0 Hz, those exposed to
      high glucose had altered calcium handling with shorter calcium transient
      durations, but larger amplitudes of the calcium transient when compared to
      controls. Additional studies are needed to elucidate a potential mechanism for
      these findings. This model provides a novel method to assess the effects of
      exposures on the cardiomyocytes' intrinsic abilities for organogenesis in 3D.

PMID- 28752325
TI  - Single-Stage Correction for Taussig-Bing Anomaly Associated With Aortic Arch
      Obstruction.
AB  - Taussig-Bing anomaly and aortic arch obstruction are two types of complex
      congenital cardiac malformations. Almost 50% of patients with Taussig-Bing
      anomaly have aortic arch obstruction. This report assesses the surgical outcomes
      of single-stage correction in neonates with both defects. Between November 2006
      and November 2015, 39 neonates with Taussig-Bing anomaly and aortic arch
      obstruction (28 patients with coarctation of the aorta and 11 patients with
      interrupted aortic arch) underwent a one-stage arterial switch operation and
      aortic reconstruction. There were three in-hospital deaths and one late death (8
      months after the surgery). The short-term survival rate was 92.3% (36/39), and
      the mid-term survival rate was 89.7% (35/39). Follow-up data were available for
      all patients who survived the operation (range 6-92 months). Echocardiology
      showed six cases of recoarctation, three cases of left ventricular outflow tract
      obstruction, three cases of right ventricular outflow tract obstruction, four
      cases of pulmonary artery stenosis, five cases of aortic regurgitation, and eight
      cases of pulmonary regurgitation. Eight patients required a reoperation during
      the follow-up period with no mortality. All survivors remained in good condition
      (New York Heart association functional class I or II). Single-stage correction of
      Taussig-Bing anomaly with aortic arch obstruction in neonates had favorable short
      and mid-term outcomes in terms of mobility and reoperation rate. The optimal
      operative procedure should be chosen according to the position of the coronary
      arteries and the type of aortic anomaly.

PMID- 28752326
TI  - Modified whole-mount in situ hybridisation and immunohistochemistry protocols
      without removal of the vitelline membrane in the appendicularian Oikopleura
      dioica.
AB  - The appendicularian Oikopleura dioica is a planktonic chordate that retains a
      tadpole shape throughout its life. Its simple and transparent body, invariant
      cell lineages, fast development and available genome and transcriptome resources
      make it a promising model organism for research in developmental biology.
      However, large-scale analysis of gene expression in O. dioica is limited owing to
      the laborious and time-consuming process of manual removal of the vitelline
      membrane, because devitellinisation of pre-hatching embryos causes failure of
      normal development. Therefore, in this study, modified procedures were developed
      for whole-mount in situ hybridisation (WISH) and immunohistochemistry (WIHC).
      This protocol enables rapid mRNA or protein detection without a manual
      devitellination step for each specimen. The critical procedure is brief treatment
      of the vitelline membrane of living embryos with 0.05% actinase E before
      fixation. Two minutes of treatment was optimal for the penetration of antisense
      RNA probes and antibodies through the vitelline membrane. This WISH protocol was
      applicable for chromogenic and fluorescent tyramide signal amplification
      reactions. Using the new protocol, we found eight genes with tissue-specific
      expression in the tail muscle, trunk epidermis, heart, pharynx, oesophagus,
      stomach or gill openings of developing larvae. This procedure also allowed for
      the detection of exogenous FLAG-tagged histone-enhanced green fluorescent protein
      by WIHC using anti-FLAG antibody. This study provides a useful and convenient
      tool for studying spatial and temporal gene expression patterns in this simple
      chordate model and should facilitate handling large amounts of genetic data from
      transcriptome-based approaches and other techniques such as treatments with
      chemical inhibitors.

PMID- 28752327
TI  - A conserved plan for wiring up the fan-shaped body in the grasshopper and
      Drosophila.
AB  - The central complex comprises an elaborate system of modular neuropils which
      mediate spatial orientation and sensory-motor integration in insects such as the
      grasshopper and Drosophila. The neuroarchitecture of the largest of these
      modules, the fan-shaped body, is characterized by its stereotypic set of
      decussating fiber bundles. These are generated during development by axons from
      four homologous protocerebral lineages which enter the commissural system and
      subsequently decussate at stereotypic locations across the brain midline. Since
      the commissural organization prior to fan-shaped body formation has not been
      previously analyzed in either species, it was not clear how the decussating
      bundles relate to individual lineages, or if the projection pattern is conserved
      across species. In this study, we trace the axonal projections from the
      homologous central complex lineages into the commissural system of the embryonic
      and larval brains of both the grasshopper and Drosophila. Projections into the
      primordial commissures of both species are found to be lineage-specific and allow
      putatively equivalent fascicles to be identified. Comparison of the projection
      pattern before and after the commencement of axon decussation in both species
      reveals that equivalent commissural fascicles are involved in generating the
      columnar neuroarchitecture of the fan-shaped body. Further, the tract-specific
      columns in both the grasshopper and Drosophila can be shown to contain axons from
      identical combinations of central complex lineages, suggesting that this columnar
      neuroarchitecture is also conserved.

PMID- 28752328
TI  - Counting on the mental number line to make a move: sensorimotor ('pen') control
      and numerical processing.
AB  - Mathematics is often conducted with a writing implement. But is there a
      relationship between numerical processing and sensorimotor 'pen' control? We
      asked participants to move a stylus so it crossed an unmarked line at a location
      specified by a symbolic number (1-9), where number colour indicated whether the
      line ran left-right ('normal') or vice versa ('reversed'). The task could be
      simplified through the use of a 'mental number line' (MNL). Many modern societies
      use number lines in mathematical education and the brain's representation of
      number appears to follow a culturally determined spatial organisation (so better
      task performance is associated with this culturally normal orientation-the MNL
      effect). Participants (counter-balanced) completed two consistent blocks of
      trials, 'normal' and 'reversed', followed by a mixed block where line direction
      varied randomly. Experiment 1 established that the MNL effect was robust, and
      showed that the cognitive load associated with reversing the MNL not only
      affected response selection but also the actual movement execution (indexed by
      duration) within the mixed trials. Experiment 2 showed that an individual's motor
      abilities predicted performance in the difficult (mixed) condition but not the
      easier blocks. These results suggest that numerical processing is not isolated
      from motor capabilities-a finding with applied consequences.

PMID- 28752329
TI  - Reward and punishment-based compound cue learning and generalization in opiate
      dependency.
AB  - Substance dependence is thought to be mediated by abnormalities in cognitive
      abilities, but how this impacts decision-making remains unclear. This study aimed
      to test whether people who are opiate dependent differed from never-dependent
      controls in learning from reward and punishment or in the generalization of
      learning to novel conditions. Participants with opiate dependency consisted of 21
      people who were outpatients in a methadone maintenance program; the control group
      consisted of 21 healthy participants with no histories of substance abuse.
      Subjects completed a computer-based task that involved two phases: the training
      phase involved participants being presented with compound stimulus (a shape and
      color) in each trial, with the goal of learning which compounds to 'pick' for
      rewards or 'skip' to avoid punishment. The test phase involved a transfer test,
      where stimuli from the first phase were combined together to form novel compounds
      without feedback. The control group demonstrated fewer errors compared to opiate
      dependent individuals during the training phase. In the test phase, controls used
      prior knowledge of both shapes and colors in responding; however, opiate
      dependent individuals used shapes but did not use their knowledge of color to
      modulate responding. When performance during training was equated in the groups
      using a learning threshold, this difference between groups on the generalization
      test remained. A deficit in learning generalization might be indicative of group
      differences in learning strategies in operation during training; however, future
      work is necessary to uncover the specific neural substrates in action during
      transfer tasks, and to determine the effects of acute methadone dosage on
      decision-making.

PMID- 28752330
TI  - Cortico-thalamic disconnection in a patient with supernumerary phantom limb.
AB  - Supernumerary phantom limb (SPL) designates the experience of an illusory
      additional limb occurring after brain damage. Functional neuroimaging during SPL
      movements documented increased response in the ipsilesional supplementary motor
      area (SMA), premotor cortex (PMC), thalamus and caudate. This suggested that
      motor circuits are important for bodily related cognition, but anatomical
      evidence is sparse. Here, we tested this hypothesis by studying an extremely rare
      patient with chronic SPL, still present 3 years after a vascular stroke affecting
      cortical and subcortical right-hemisphere structures. Anatomical analysis
      included an advanced in vivo reconstruction of white matter tracts using
      diffusion-based spherical deconvolution. This reconstruction demonstrated a
      massive and relatively selective disconnection between anatomically preserved
      SMA/PMC and the thalamus. Our results provide strong anatomical support for the
      hypothesis that cortico-thalamic loops involving motor-related circuits are
      crucial to integrate sensorimotor processing with bodily self-awareness.

PMID- 28752331
TI  - The association of neighborhood context with health outcomes among ethnic
      minority breast cancer survivors.
AB  - While individual-level determinants of health, such as education and income, have
      been well documented among breast cancer survivors, little is known about the
      role of neighborhood context on survivorship outcomes among this population. The
      present study examined the association of neighborhood stress with multiple
      health outcomes among ethnic minority breast cancer survivors (BCS). A mixed
      methods approach was used to recruit 320 African-American and Hispanic BCS who
      were 26-89 years and lived in metropolitan Los Angeles, CA. Neighborhood stress
      was assessed by six items taken from the Life Stress Scale. Health outcomes
      included (1) self-rated health, measured by the Short-Form-36 Health Survey, (2)
      number of comorbidities (0-14), (3) depressive symptoms, assessed by the Center
      for Epidemiological Studies-Depression scale, and (4) psychological difficulties.
      Greater neighborhood stress was significantly associated with poorer self
      reported health (adjusted beta = -.22, 95% confidence interval [CI] -.40, -.05),
      greater number of comorbidities (adjusted risk ratio = .19, 95% CI .07, .30),
      more depressive symptoms (adjusted beta = .10, 95% CI .06, .15), and a higher
      likelihood of psychological difficulties (adjusted odds ratio = 2.28, 95% CI
      1.51, 3.45) among ethnic minority BCS. These findings underscored the importance
      of taking neighborhood context into account in examining the determinants of
      health, survivorship, and quality of life outcomes among cancer patients. Our
      findings may inform population health, health services, and interventions
      addressing neighborhood and individual-level factors to promote post treatment
      health and survivorship outcomes as well as to identify high-risk patients,
      especially among medically vulnerable communities.

PMID- 28752334
TI  - Erratum to: A Modeling Study of the Responses of the Lateral Superior Olive to
      Ipsilateral Sinusoidally Amplitude-Modulated Tones.

PMID- 28752332
TI  - Adverse bone effects of medications used to treat non-skeletal disorders.
AB  - There is a growing list of medications used to treat non-skeletal disorders that
      cause bone loss and/or increase fracture risk. This review discusses
      glucocorticoids, drugs that reduce sex steroids, antidiabetic agents, acid
      reducing drugs, selective serotonin reuptake inhibitors, and heparin. A number of
      drugs are known to cause bone loss, increase fracture risk, or both. These drugs
      should be used in the lowest dose necessary to achieve the desired benefit and
      for the shortest time necessary, but in many cases, long-term treatment is
      required. Effective countermeasures are available for some.

PMID- 28752333
TI  - Significance of long chain polyunsaturated fatty acids in human health.
AB  - In the last decades, the development of new technologies applied to lipidomics
      has revitalized the analysis of lipid profile alterations and the understanding
      of the underlying molecular mechanisms of lipid metabolism, together with their
      involvement in the occurrence of human disease. Of particular interest is the
      study of omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFAs),
      notably EPA (eicosapentaenoic acid, 20:5n-3), DHA (docosahexaenoic acid, 22:6n
      3), and ARA (arachidonic acid, 20:4n-6), and their transformation into bioactive
      lipid mediators. In this sense, new families of PUFA-derived lipid mediators,
      including resolvins derived from EPA and DHA, and protectins and maresins derived
      from DHA, are being increasingly investigated because of their active role in the
      "return to homeostasis" process and resolution of inflammation. Recent findings
      reviewed in the present study highlight that the omega-6 fatty acid ARA appears
      increased, and omega-3 EPA and DHA decreased in most cancer tissues compared to
      normal ones, and that increments in omega-3 LC-PUFAs consumption and an omega
      6/omega-3 ratio of 2-4:1, are associated with a reduced risk of breast, prostate,
      colon and renal cancers. Along with their lipid-lowering properties, omega-3 LC
      PUFAs also exert cardioprotective functions, such as reducing platelet
      aggregation and inflammation, and controlling the presence of DHA in our body,
      especially in our liver and brain, which is crucial for optimal brain
      functionality. Considering that DHA is the principal omega-3 FA in cortical gray
      matter, the importance of DHA intake and its derived lipid mediators have been
      recently reported in patients with major depressive and bipolar disorders,
      Alzheimer disease, Parkinson's disease, and amyotrophic lateral sclerosis. The
      present study reviews the relationships between major diseases occurring today in
      the Western world and LC-PUFAs. More specifically this review focuses on the
      dietary omega-3 LC-PUFAs and the omega-6/omega-3 balance, in a wide range of
      inflammation disorders, including autoimmune diseases. This review suggests that
      the current recommendations of consumption and/or supplementation of omega-3 FAs
      are specific to particular groups of age and physiological status, and still need
      more fine tuning for overall human health and well being.

PMID- 28752335
TI  - Risk factors for morbidity after appendectomy.
AB  - INTRODUCTION: The aim of the present study was to evaluate the risk factors for
      postoperative complications after an appendectomy with special regard to both the
      time period from hospital admission to operation and night time surgery. PATIENTS
      AND METHODS: Patients who underwent an appendectomy due to acute appendicitis and
      were admitted to the University Hospital Aachen between January 2003 and January
      2014 were included in this retrospective analysis. Regarding the occurrence of
      postoperative complications, patients were divided into the following two groups:
      the group with complications (group 1) and the group without complications (group
      2). RESULTS: Of the 2136 patients who were included in this study, 165 patients
      (group 1) exhibited complications, and in 1971 patients (group 2), no
      complications appeared. After a univariate logistic regression analysis, six
      predictors for postoperative complications were found and are described as
      follows: (1) complicated appendicitis (odds ratio (OR) 4.8 (3.46-6.66), p <
      0.001), (2) operation at night (OR 1.62 (1.17-2.24), p = 0.004), (3) conversion
      from laparoscopic to open access (OR 37.08 (12.95-106.17), p < 0.001), (4) an age
      > 70 years (OR 6.00 (3.64-9.89), p < 0.001), (5) elevated CRP (OR 1.01 (1.01
      1.01), p < 0.001) and (6) increased WBC count (OR 1.04 (1.01-1.07), p = 0.003).
      After multivariate logistic regression analysis, a significant association was
      demonstrated for complicated appendicitis (1.88 (1.06-3.32), p < 0.031),
      conversion to open access (OR 16.33 (4.52-58.98), p < 0.001), elevated CRP (OR
      1.00 (1.00-1.01), p = 0.017) and an age > 70 years (OR 3.91 (2.12-7.21), p <
      0.001). The time interval between hospital admission and operation was not
      associated with postoperative complications in the univariate and multivariate
      logistic regression analyses, respectively. However, the interaction between
      complicated appendicitis and the time interval to operation was significant (OR
      1.024 (1.00-1.05), p = 0.028). CONCLUSION: Based on our findings, surgical delay
      in the case of appendicitis and operation at night did not increase the risk for
      postoperative complications. However, the mean waiting time was less than 12 h
      and patients aged 70 years or older were at a higher risk for postoperative
      complications. Furthermore, for the subgroup of patients with complicated
      appendicitis, the time interval to surgery had a significant influence on the
      occurrence of postoperative complications. Therefore, the contemporary operation
      depending on the clinical symptoms and patient age remains our recommendation.

PMID- 28752336
TI  - Acute appendicitis in children: can surgery be postponed? Short-term results in a
      cohort of 225 children.
AB  - PURPOSE: To our knowledge, there is no German study, which has examined the
      relationship between a postponement of surgery (from emergency service to
      standard working time) and the corresponding risk of postoperative complications
      in children and adolescents with acute appendicitis. The aim of this study is to
      examine if surgery of acute appendicitis in childhood can be postponed from night
      shift to the next working day without negative effects for the patient. METHODS:
      In a retrospective analysis (September 2001 to June 2007), the files of 225
      paediatric surgical patients with acute appendicitis have been analysed
      concerning history, histology, course of treatment and development of
      complications. The cohort was divided into groups by their histology (common,
      "A", complicated appendicitis, "B") and by the median time (10 h) from admission
      to surgery (immediate, "C", delayed surgery, "D"). These groups have been
      analysed and compared. RESULTS: Groups A and B did not differ concerning time to
      admittance (p = 0.922). Seven patients developed complications (n = 7/225, 3.1%).
      Six complications were seen in group C (n = 6/113, 5.3%) compared to 1 in group D
      (n = 1/112, 0.9%), the difference was not significant (p = 0.119). None of the
      patients of group B developed complications after delayed surgery. Median follow
      up was 10 days (IQR 7-15). CONCLUSIONS: In view of the development of
      complications, there was no evidence that the time between inpatient admission
      and surgery had any impact on the postoperative result. Thus, there is usually no
      need to perform surgery in common appendicitis during night shift.

PMID- 28752338
TI  - Exploring the peptide retention mechanism in molecularly imprinted polymers.
AB  - Molecularly imprinted polymers (MIPs) have been used as useful sorbents in solid
      phase extraction for a wide range of molecules and sample matrices. Their unique
      selectivity can be fine-tuned in the imprinting process and is crucial for the
      extraction of macromolecules from complex matrices such as serum. A relevant
      example of this is the application of MIPs to peptides in diagnostic assays. In
      this article the selectivity of MIPs, previously implemented in a quantitative
      mass-spectrometric assay for the biomarker pro-gastrin-releasing peptide, is
      investigated. Partial least squares regression was used to generate models for
      the evaluation and prediction of the retention mechanism of MIPs. A hypothesis on
      interactions of MIPs with the target peptide was verified by ad hoc experiments
      considering the relevant peptide physicochemical properties highlighted from the
      multivariate analysis. Novel insights into and knowledge of the driving forces
      responsible for the MIP selectivity have been obtained and can be directly used
      for further optimization of MIP imprinting strategies. Graphical Abstract Applied
      analytical strategy: the Solid Phase Extraction (SPE) of digested Bovin Serum
      Albumin (BSA), using Molecularly Imprinted Polymers (MIP), is followed by the
      liquid chromatography-mass spectrometry (LC-MS) analysis for the identification
      of the retained peptides. The further application of multivariate analysis allows
      setting up a Partial Least Square (PLS) model, which describes the peptide
      retention into the MIP and gives additional knowledge to be used in the
      optimization of the MIP and the whole SPE method.

PMID- 28752339
TI  - The 116th Annual Scientific Meeting of the American Society of Colon and Rectal
      Surgeons.

PMID- 28752340
TI  - Importance of the Moskowitz artery in the laparoscopic medial approach to splenic
      flexure mobilization: a cadaveric study.
AB  - BACKGROUND: The medial approach in laparoscopic splenic flexure mobilization is
      based on the entrance to the lesser sac just above the ventral edge of the
      pancreas (VEOP). The artery of Moskowitz runs through the base of the mesocolon,
      just above the VEOP. The aim of this study was to assess the incidence of the
      artery of Moskowitz, its route and its distance from the VEOP. METHODS: We
      performed a cadaveric study on 27 human cadavers. The vascular arcades of the
      splenic flexure were dissected, the number of vascular arches, and the origin and
      localization of its terminal anastomosis were recorded. The splenic flexure
      avascular space (SFAS) was defined as the avascular zone in the mesocolon
      delimited by the VEOP, middle colic artery, ascending branch of the left colic
      artery and the vascular arch of the splenic flexure nearest to the VEOP and was
      quantified as the distance between the VEOP and the most proximal arch RESULTS:
      The artery of Drummond was identified in 100% of the cadavers. In 5 of 27 (18%)
      Riolan's arch was present, and in 3 of 27 (11%) the Moskowitz artery was found.
      The mean distance from the VEOP to the artery of Moskowitz was 0.3 cm (SD 0.04).
      This vascular arch travelled from the origin of the middle colic artery to the
      distal third of the ascending branch of the left colic artery. The SFAS was
      greater (p = 0.001) in cadavers that only presented the artery of Drummond (mean
      6.8 cm; SD 1.25) than in those with Riolan's arch (mean 4.5 cm; SD 0.5)
      CONCLUSIONS: In the medial approach for laparoscopic mobilization of the splenic
      flexure, when only one of the arches is present, the avascular area is an
      extensive and secure territory. If the artery of Moskowitz is present, the area
      is nonexistent and this would contraindicate the approach due to risk of
      iatrogenic bleeding. A radiological preoperatory study could be essential for
      accurate and safe surgery in this area.

PMID- 28752341
TI  - Comparative Correlation Between Chemical Composition and Cytotoxic Potential of
      the Coral-Associated Fungus Aspergillus sp. 2C1-EGY Against Human Colon Cancer
      Cells.
AB  - Cancer is a leading cause of death in several countries. In the search for new
      anticancer drugs, marine organisms have played an important role in the discovery
      of lead compounds and the development of new pharmaceuticals for their wide
      diversity of chemical structures and biological activities. In the present study,
      the cytotoxicity on colorectal cancer cells HCT116 exerted by marine fungus
      Aspergillus sp. 2C1-EGY extracts associated with the soft coral Sinularia sp. was
      investigated; the sub-fractions Fr 2c and Fr 2d had significantly high cytotoxic
      activity (88 and 85%, respectively). Moreover, the major hexadecanoic,
      octadecanoic, and octadecenoic acids as well as their methyl esters were
      isolated. GC/MS analysis revealed the identification of 46 major and minor
      compounds, from which 19 saturated and unsaturated fatty acids and eight fatty
      acid esters were identified.

PMID- 28752342
TI  - Erratum to: Distal pain and carpal tunnel syndrome diagnosis among cashiers: a
      longitudinal study.

PMID- 28752343
TI  - Erratum to: Lessons learned from comparing molecular dynamics engines on the
      SAMPL5 dataset.

PMID- 28752344
TI  - Molden 2.0: quantum chemistry meets proteins.
AB  - Since the first distribution of Molden in 1995 and the publication of the first
      article about this software in 2000 work on Molden has continued relentlessly. A
      few of the many improved or fully novel features such as improved and broadened
      support for quantum chemistry calculations, preparation of ligands for use in
      drug design related softwares, and working with proteins for the purpose of
      ligand docking.

PMID- 28752345
TI  - Structure-reactivity modeling using mixture-based representation of chemical
      reactions.
AB  - We describe a novel approach of reaction representation as a combination of two
      mixtures: a mixture of reactants and a mixture of products. In turn, each mixture
      can be encoded using an earlier reported approach involving simplex descriptors
      (SiRMS). The feature vector representing these two mixtures results from either
      concatenated product and reactant descriptors or the difference between
      descriptors of products and reactants. This reaction representation doesn't need
      an explicit labeling of a reaction center. The rigorous "product-out" cross
      validation (CV) strategy has been suggested. Unlike the naive "reaction-out" CV
      approach based on a random selection of items, the proposed one provides with
      more realistic estimation of prediction accuracy for reactions resulting in novel
      products. The new methodology has been applied to model rate constants of E2
      reactions. It has been demonstrated that the use of the fragment control domain
      applicability approach significantly increases prediction accuracy of the models.
      The models obtained with new "mixture" approach performed better than those
      required either explicit (Condensed Graph of Reaction) or implicit (reaction
      fingerprints) reaction center labeling.

PMID- 28752346
TI  - Neuro-ophthalmological findings in TAFRO syndrome in a patient from South
      America, a variant of multicentric Castleman's disease.
AB  - BACKGROUND: To report the neuro-ophthalmological findings in the TAFRO syndrome
      in a South American patient. METHODS: This is a case report of a patient with
      TAFRO syndrome. RESULTS: We present the case of a 66-year-old woman with TAFRO
      syndrome and multicentric Castleman disease, who developed ophthalmic
      manifestations, as a rare complication, including optic disk edema and serous
      retinal detachment, which improved with conventional therapy. CONCLUSIONS: The
      optic disk edema could be present as a neuro-ophthalmological finding in TAFRO
      syndrome. To the best of our knowledge, this is the first report on the
      ophthalmic manifestations in the TAFRO syndrome.

PMID- 28752347
TI  - [Prolonged neuroleptic malignant syndrome after Haloperidol injection].
AB  - Neuroleptic malignant syndrome (NMS) is a rare disorder caused by drug-induced
      dopamine-receptor-blockage or low dopamine concentration in the brain. It is a
      severe reaction to neuroleptic drugs in antipsychotic therapy. Symptoms in NMS
      typically consist of fever, muscle rigidity and cognitive changes; laboratory
      findings include elevated infectious disease markers and creatine kinase as well
      as signs of rhabdomyolysis. To differentiate NMS from other malignant
      hyperthermia syndromes identifying the offending drug and clinical history are
      essential. Therapy in NMS includes withdrawal of the causative medication and
      intensive care treatment possibly with administration of dantrolene.In this case
      report, we describe the clinical course of a 48 year old man who developed
      typical clinical symptoms and laboratory parameters of malignant hyperthermia
      syndrome after injection of haloperidol.

PMID- 28752348
TI  - Prevalence of vitamin D deficiency in otherwise healthy individuals between the
      ages of 18 and 90 years in southeast Turkey.

PMID- 28752349
TI  - Citicoline in severe traumatic brain injury: indications for improved outcome : A
      retrospective matched pair analysis from 14 Austrian trauma centers.
AB  - Goal-oriented management of traumatic brain injury (TBI) can save the lives
      and/or improve the long-term outcome of millions of affected patients worldwide.
      Additionally, enhancing quality of life will save enormous socio-economic costs;
      however, promising TBI treatment strategies with neuroprotective agents, such as
      citicoline (CDP-choline), lacked evidence or produced contradictory results in
      clinical trials. During a prehospital TBI project to optimize early TBI care
      within 14 Austrian trauma centers, data on 778 TBI patients were prospectively
      collected. As preceding evaluations suggested a beneficial outcome in TBI
      patients treated at the Wiener Neustadt Hospital (WNH), we aimed to investigate
      the potential role of citicoline administration, solely applied in WNH, in those
      patients. In a retrospective subgroup analysis we compared 67 patients from WNH
      with citicoline administration and 67 matched patients from other Austrian
      centers without citicoline use. Patients with Glasgow Coma Scale score <13 on
      site and/or Abbreviated Injury Scale of the region "head" >2 were included. Our
      analysis revealed significantly reduced rates of intensive care unit (ICU)
      mortality (5% vs. 24%, p < 0.01), in-hospital mortality (9% vs. 24%, p = 0.035)
      and 6-month mortality (13% vs. 28%, p = 0.031), as well as of unfavorable outcome
      (34% vs. 57%, p = 0.015) and observed vs. expected ratio for mortality (0.42 vs.
      0.84) in the WNH (citicoline receivers) group. Despite the limitations of a
      retrospective subgroup analysis our findings suggest a possible correlation
      between early and consequent citicoline administration and beneficial outcomes.
      Therefore, we aim to set up an initiative for a prospective, multicenter
      randomized controlled trial with citicoline in sTBI (severe TBI) patients.

PMID- 28752350
TI  - Lung transplantation for bronchiolitis obliterans syndrome after allogenic
      hematopoietic stem cell transplantation.
AB  - Bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell
      transplantation (HSCT) is a major cause of morbidity and mortality with limited
      treatment options. Lung transplantation (LTX) has been rarely reported as a
      treatment option for selected HSCT recipients with this problem. In the present
      study, we reported six patients who underwent LTX due to BOS after HSCT (two
      females, four males) from January 2012 to December 2014 in our center. The median
      time from HSCT to diagnosis of BOS was 2.5 years (ranging from 1 to 5 years). At
      a median time of 4 years (ranging from 2 to 5 years) after diagnosis of BOS, four
      patients received bilateral sequential LTX, and two patients received single LTX.
      One of the recipients suffered from mild acute rejection after LTX, another
      suffered from primary lung graft dysfunction on post-operation day 2, and three
      experienced fungal infections. The median time for follow-up after LTX was 19.5
      months (ranging from 12 to 39 months). At present, all patients are alive with
      good functional capacity and no relapse of BOS and hematologic malignancy
      conditions. Patients who received bilateral LTX have better pulmonary functions
      than patients who received single LTX.

PMID- 28752351
TI  - The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a
      systematic review and meta-analysis.
AB  - The aim of this study was to evaluate the evidence regarding the neutrophil-to
      lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer
      patients. A search of PubMed and Embase for relevant studies between January 1,
      1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil
      lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion
      required studies published in English containing bladder cancer patients and
      evaluating NLR as a predictive factor. Endpoints of NLR and survival data were
      extracted for pooled analysis. The pooled results showed that an elevated NLR was
      a predictor for poor overall survival (OS) [hazard ratio (HR) = 1.19, 95%
      confidence interval (CI) 1.07-1.31], cancer-specific survival (CSS) (HR = 1.40,
      95% CI 1.17-1.69), recurrence-free survival (RFS) (HR = 1.58, 95% CI 1.24-2.03)
      and progression-free survival (PFS) (HR = 1.33, 95% CI 1.19-1.49) in patients
      with bladder cancer. Heterogeneity between studies was observed for OS, CSS and
      RFS, but not for PFS. Publication bias was detected for all these outcomes. Our
      results showed that elevated NLR might be valuable as a predictive factor of
      survival in bladder cancer patients.

PMID- 28752352
TI  - Presurgical axitinib therapy increases fibrotic reactions within tumor thrombus
      in renal cell carcinoma with thrombus extending to the inferior vena cava.
AB  - BACKGROUND: Clinical benefits of presurgical axitinib therapy for renal cell
      carcinoma (RCC) extending into the inferior vena cava (IVC) remain unclear. We
      aimed to investigate surgical benefits and pathological antitumor effects of
      presurgical axitinib therapy for RCC with IVC thrombus. METHODS: Of 56
      consecutive RCC patients with IVC thrombus between January 1994 and December
      2016, 41 patients who underwent radical nephrectomy (RN) were categorized as
      upfront RN (Upfront group) or presurgical axitinib followed by RN (Presurgical
      group). We retrospectively evaluated safety, radiologic tumor responses, and Ki
      67 proliferation index before and after axitinib administration in the
      Presurgical group. Surgical outcomes, postoperative complications, and fibrosis
      within the IVC thrombus were compared between the Upfront and Presurgical groups.
      RESULTS: The number of patients in the Upfront and Presurgical groups was 31 and
      10, respectively. Major presurgical axitinib-related adverse events were grade 2
      or 3 hypertension (50%). The median radiological tumor response in the renal
      tumor, IVC thrombus length, and IVC thrombus volume were -19%, -21 mm, and -54%,
      respectively. The fibrosis within the IVC thrombus was significantly higher in
      the Presurgical group (10%) than in the Upfront group (3.4%). The Ki-67
      proliferation index was significantly decreased in RN specimens (7.3%) versus
      needle biopsy specimens (23%) in the Presurgical group. Blood loss and operative
      duration were significantly lower and shorter, respectively, in the Presurgical
      group than in the Upfront group. CONCLUSIONS: Presurgical axitinib therapy
      enhanced tumor reduction accompanied by fibrosis and may contribute to surgical
      risk reduction for selected patients.

PMID- 28752353
TI  - Readiness for Antiretroviral Therapy: Implications for Linking HIV-Infected
      Individuals to Care and Treatment.
AB  - Using survey data collected immediately after referral for ART (N = 87), this
      study examined ART-readiness among individuals (18 years and older) attending a
      mobile health clinic in South Africa. Most participants reported being very ready
      (84%) and motivated (85%) to start ART, but only 72% were assessed as ready for
      ART on all measures. Treatment readiness was lower among individuals who did not
      think they would test HIV-positive (aOR 0.26, p < 0.05) and among individuals who
      reported being in good health (aOR 0.44, p < 0.1). In contrast, higher readiness
      was associated with better ART knowledge (aOR 4.31, p < 0.05) and knowing someone
      who had experienced positive health effects from ART (aOR 2.65, p < 0.05).
      Results indicate that post-test counselling will need to be designed to deal with
      surprise at HIV diagnosis, and that health messaging needs to be carefully
      crafted to support uptake of ART among HIV-positive but healthy individuals.
      Further research is needed on effective post-test counselling approaches and
      effective framing of health messaging to increase awareness of the multiple
      positive benefits of early ART initiation and corresponding readiness to engage
      in treatment.

PMID- 28752354
TI  - Acceptability of Daily Use of Free Oral Pre-exposure Prophylaxis (PrEP) Among
      Transgender Women Sex Workers in Shenyang, China.
AB  - This study investigated the acceptability of daily use of free oral pre-exposure
      prophylaxis (PrEP) and associated factors among transgender women sex workers in
      Shenyang, China, following a briefing on PrEP. A total of 183 HIV negative or
      sero-status unknown participants completed the cross-sectional survey. The
      prevalence of acceptability of daily use of free oral PrEP was 61.2%. Adjusting
      for education level and monthly income, variables on negative attitudes toward
      PrEP (i.e., having concerns about the side-effects of PrEP) [Adjusted odds ratios
      (AOR): 0.26], perceived subjective norms (i.e., perceiving support from male
      partners to take PrEP) (AOR: 2.08), and perceived behavioral control (e.g.,
      perceiving complete control over using PrEP) (AOR: 2.10-16.72) were significantly
      associated with acceptability of daily use of free oral PrEP. In addition,
      experiencing violence during sex work, perceived risk of contracting HIV from
      clients and probable anxiety were also significant. Future PrEP promotion
      campaigns should consider these factors.

PMID- 28752355
TI  - Trichostatin A increases embryo and green plant regeneration in wheat.
AB  - KEY MESSAGE: Chemical agents such as trichostatin A (TSA) can assist in
      optimization of doubled haploidy for rapid improvements in wheat germplasm and
      addressing recalcitrance issues in cell culture responses. In wheat, plant
      regeneration through microspore culture is an integral part of doubled haploid
      (DH) production. However, low response to tissue culture and genotype specificity
      are two major constraints in the broad deployment of this breeding tool.
      Recently, the structure of chromatin was shown to be linked with cell transitions
      during tissue culture. Specifically, repression of genes that are required for
      cell morphogenesis, through acetylation of histones, may play an important role
      in this process. Reduction of histone acetylation by chemical inhibition may
      increase tissue culture efficiency. Here, the role of trichostatin A (TSA) in
      inducing microspore-derived embryos was investigated in wheat. The optimal dose
      of TSA was determined for wheat cultivars and subsequently validated in F1
      hybrids. A significant increase in the efficiency of DH production was observed
      in both cultivated varieties and F1 hybrids. Thus, the inclusion of TSA in DH
      protocols for wheat breeding programs is advocated.

PMID- 28752356
TI  - Capsule commentary on Jones et al., "Connecting the Dots": a Qualitative Study of
      Home Health Nurse Perspectives on Coordinating Care for Recently-Discharged
      Patients.

PMID- 28752357
TI  - Capsule Commentary on Klein et al., Categorical Risk Perception Drives
      Variability in Antibiotic Prescribing in the Emergency Department: a Mixed
      Methods Observational Study.

PMID- 28752358
TI  - Capsule Commentary on VanGompel et al., Incidence and Predictors of Repeat Bone
      Mineral Densitometry: A Longitudinal Cohort Study.

PMID- 28752359
TI  - Irrational Exuberance in Medicine.

PMID- 28752360
TI  - Anatomical characteristics of greater palatine foramen: a novel point of view.
AB  - PURPOSE: Anatomy of greater palatine foramen is important for maxillary nerve
      blocks, haemostatic procedures, and the treatment of neuralgia; although metrical
      data are available about its collocation, still several aspects need to be
      explored, such as the influence of the cranium size. METHODS: The position of
      greater palatine foramen was assessed on 100 skulls through six measurements
      (distances from intermaxillary suture, posterior palatal border, posterior nasal
      spine, and incisive foramen; palatal length; relative position on palatal length)
      and two angles (angles at incisive foramen and greater palatine foramen). Maximum
      cranial length, maximum cranial breadth, cranial height and bizygomatic breadth,
      horizontal cephalic index, and Giardina Y-index were evaluated. Possible
      differences according to sex and side were assessed through two-way ANOVA (p <
      0.05). Measurements showing sexual dimorphism were further assessed through one
      way ANCOVA including cranial parameters as covariates (p < 0.05). RESULTS:
      Distances of the greater palatine foramen from intermaxillary suture, incisive
      foramen, posterior palatal border, posterior nasal spine, palatal length, and
      position of the greater palatine foramen on the palatal length were statistically
      different according to sex (p < 0.05), independently from general cranial
      dimensions but for the distance from the posterior palatal border. The angle at
      the incisive foramen and distances from intermaxillary suture and from posterior
      nasal spine showed statistically significant differences according to side (p <
      0.05). CONCLUSIONS: Results highlight that most of sexually dimorphic
      measurements useful for pinpointing the greater palatal foramen do not depend
      upon the cranium size. A more complete metrical assessment of the localization of
      the greater palatine foramen was provided.

PMID- 28752361
TI  - The role of preoperative C-reactive protein and procalcitonin as predictors of
      post-pancreaticoduodenectomy infective complications: A prospective observational
      study.
AB  - INTRODUCTION: The common causes of morbidity after pancreaticoduodenectomy (PD)
      are infective complications. Till date, no specific preoperative markers have
      been identified to determine the probability of developing infective
      complications. We have studied the factors predicting the occurrence of the
      infective complication/s in the present study. METHODS: The present prospective
      observational study included 133 consecutive patients who underwent PD from
      January 2011 to June 2016 at a specialized hepatopancreaticobiliary surgical
      oncology unit. The surgeries were done using a standardized technique.
      Postoperative complications were segregated into two categories-(a) infective
      (e.g. cholangitis) and (b) non-infective (e.g. delayed gastric emptying).
      Increased age, preoperative serum albumin levels, preoperative biliary stenting,
      pre-stenting serum bilirubin levels, duration of common bile duct stenting,
      preoperative C-reactive protein [CRP], and procalcitonin [PCT] were evaluated.
      RESULTS: Overall morbidity rate was 48.8%. Morbidity associated with infective
      complications was 21.8%. Increased age, preoperative serum albumin levels, and
      pre-stenting serum bilirubin levels did not increase the rate of the infective
      complications. The association between preoperative PCT and preoperative CRP with
      the infective complications was significant with a p-value of <0.01 (6.75E-07)
      and <0.01 (4.80E-10), respectively. In the multivariate analysis, only the
      elevated preoperative procalcitonin was a statistically significant predictor of
      postoperative infective complications. CONCLUSION: Preoperative PCT and CRP
      levels done 48 h before surgery are sensitive, specific, easily available, and
      cost-effective predictors of infective complications after PD.

PMID- 28752362
TI  - Necrostatin-1 Protects Against D-Galactosamine and Lipopolysaccharide-Induced
      Hepatic Injury by Preventing TLR4 and RAGE Signaling.
AB  - Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome results
      in massive inflammation and hepatocyte death. Necroptosis is a regulated form of
      necrotic cell death that is emerging as a crucial control point for inflammatory
      diseases. The kinases receptor interacting protein (RIP) 1 and RIP3 are known as
      key modulators of necroptosis. In this study, we investigated the impact of
      necroptosis in the pathogenesis of FHF and molecular mechanisms, particularly its
      linkage to damage-associated molecular pattern (DAMP)-mediated pattern
      recognition receptor (PRR) signaling pathways. Male C57BL/6 mice were given an
      intraperitoneal injection of necrostatin-1 (Nec-1, RIP1 inhibitor; 1.8 mg/kg;
      dissolved in 2% dimethyl sulfoxide in phosphate-buffered saline) 1 h before
      receiving D-galactosamine (GalN; 800 mg/kg)/lipopolysaccharide (LPS; 40 MUg/kg).
      Hepatic RIP1, RIP3 protein expression, their phosphorylation, and RIP1/RIP3
      complex formation upregulated in the GalN/LPS group were attenuated by Nec-1. Nec
      1 markedly reduced the increases in mortality and serum alanine aminotransferase
      activity induced by GalN/LPS. Increased serum high mobility group box 1 (HMGB1)
      and interleukin (IL)-33 release, HMGB1-toll-like receptor 4 and HMGB1-receptor
      for advanced glycation end products (RAGE) interaction, and nuclear protein
      expressions of NF-kappaB and early growth response protein-1 (egr-1) were
      attenuated by Nec-1. Our finding suggests that necroptosis is responsible for
      GalN/LPS-induced liver injury through DAMP-activated PRR signaling.

PMID- 28752363
TI  - Inhibition of Endoplasmic Reticulum Stress Alleviates Lung Injury Induced by
      Brain Death.
AB  - Brain death (BD) can induce inflammation and injury of organs. Endoplasmic
      reticulum (ER) stress is associated with a variety of diseases. However, little
      is known about how ER stress is implicated in brain death (BD)-induced lung
      injury. In this study, a stable BD rat model was constructed to investigate the
      role of ER stress on BD-induced lung injury. H&E staining demonstrated that BD
      can induce lung injury in rats. The results of Western blot and
      immunohistochemistry showed that apoptosis was observed in the lung tissues of BD
      rats. And the level of GRP78, p-PERK, p-eIF2alpha, CHOP, and Caspase-12 was
      highly expressed in BD rats compared with the control group. Inhibition of ER
      stress with salubrinal reduced the BD-induced lung inflammation. Moreover, BD
      induced increase of NF-kappaB activity was lowered by inhibition of ER stress.
      These results suggested that inhibition of ER stress alleviates BD-induced lung
      inflammation by regulating NF-kappaB signaling pathway.

PMID- 28752364
TI  - Socio-demographic Moderators of Associations Between Psychological Factors and
      Latinas' Breast Cancer Screening Behaviors.
AB  - This study tested whether socio-demographic factors moderated associations
      between psychological factors and Latinas' breast cancer screening behaviors. 222
      churchgoing Latinas (40-65 years) in San Diego, CA completed surveys assessing
      socio-demographics (e.g., income and acculturation), psychological factors (e.g.,
      perceived barriers to screening), and cancer screening behaviors. Multilevel
      models examined associations of socio-demographic and psychological factors (and
      their interactions) with adherence to annual mammography or clinical breast exam
      (CBE) screening. Although no main effects were found, there were moderation
      effects. Acculturation moderated associations between perceived barriers to
      screening and both screening outcomes, with inverse associations only among the
      high-acculturation group. Education moderated the relationship between perceived
      barriers to screening and CBE screening, with an inverse association only among
      the low-education group. Marital status moderated the relationship between
      depressive symptoms and CBE screening, with an inverse association only among
      single/non-partnered participants. Interventions are needed targeting
      psychological barriers to breast cancer screening among Latinas.

PMID- 28752365
TI  - Alternative reagents to antibodies in imaging applications.
AB  - Antibodies have been indispensable tools in molecular biology, biochemistry and
      medical research. However, a number of issues surrounding validation, specificity
      and batch variation of commercially available antibodies have prompted research
      groups to develop novel non-antibody binding reagents. The ability to select
      highly specific monoclonal non-antibody binding proteins without the need for
      animals, the ease of production and the ability to site-directly label has
      enabled a wide variety of applications to be tested, including imaging. In this
      review, we discuss the success of a number of non-antibody reagents in imaging
      applications, including the recently reported Affimer.

PMID- 28752366
TI  - [Toni-Haid-Travel Grant for neurootologic research of the Working Group of German
      speaking Audiologists, Neurootologists and Otologists].

PMID- 28752367
TI  - Update on Quinolone Allergy.
AB  - PURPOSE OF REVIEW: Quinolones are a group of synthetic antibiotics widely use as
      first-line treatment for many infections. There has been an increase in the
      incidence of hypersensitivity reactions to quinolones in recent years, likely due
      to increased prescription. The purpose of this review is to summarize the
      clinical pictures, the methods used for diagnosing and the management of allergic
      reactions to quinolones. RECENT FINDINGS: Allergic reactions to quinolones can be
      immediate or delayed, being anaphylaxis and maculopapular exanthema respectively
      the most frequent clinical entities. A precise diagnosis is particularly
      difficult since clinical history is often unreliable, skin tests can induce false
      positive results, and commercial in vitro test are not well validated. Therefore,
      drug provocation testing is considered the gold standard to establish diagnosis,
      which is not a risk-free procedure. Cross-reactivity between quinolones is
      difficult to predict due to the small number of patients included in the few
      published studies. Moreover, hypersensitivity to quinolones has also been
      associated with beta-lactam and neuromuscular blocking agent allergies, although
      further studies are needed to understand the underlying mechanisms. Avoidance of
      the culprit quinolone is indicated in patients with a diagnosis of
      hypersensitivity to these drugs. When quinolone treatment is the only therapeutic
      option available, desensitization is necessary. This review summarizes the
      complex diagnostic approach and management of allergic reactions to quinolones.

PMID- 28752368
TI  - Long-term follow-up of conjunctival melanoma treated with topical interferon
      alpha-2b eye drops as adjunctive therapy following surgical resection.
AB  - PURPOSE: The purpose of this study was to report the clinical outcomes of
      patients with conjunctival melanoma treated with interferon (IFN) alpha-2b eye
      drops following local tumor resection. METHODS: Five eyes of five patients were
      enrolled in this study. All patients underwent the local resection of tumors, and
      topical IFNalpha-2b eye drops were subsequently administered 4 times/day until
      the complete disappearance of the pigmented lesions determined by slit-lamp
      examination. Ophthalmological findings, histopathological findings, and imaging
      modalities were retrospectively analyzed. RESULTS: The age of the patients ranged
      from 65 to 84 years (mean: 75.4 years). Locations of the tumor were the bulbar
      conjunctiva in three eyes, multiple palpebral conjunctivas in one eye, and
      palpebral conjunctiva and caruncle in one eye. All patients received topical
      IFNalpha-2b eye drop treatment for 6-10 months. Follow-up periods after resection
      ranged from 18 to 78 months. Histologically, all excised conjunctival tumors were
      diagnosed with malignant melanoma, where the surgical margins were completely
      negative in one patient. No patients had suffered from severe adverse effects
      related to IFNalpha-2b. Four out of five patients consequently achieved complete
      remission. Since one eye in one case showed resistance to the local chemotherapy
      containing IFNalpha-2b eye drops and the subconjunctival injection of IFN-beta,
      orbital exenteration was eventually required 12 months after local resection.
      CONCLUSIONS: Topical IFNalpha-2b eye drops may be safe and one of the useful
      adjunctive treatments following surgical resection for patients with conjunctival
      melanoma.

PMID- 28752369
TI  - Ranibizumab versus dexamethasone implant for central retinal vein occlusion:
      special remarks of the RANIDEX study.

PMID- 28752370
TI  - Post-hypoxic constriction of retinal arterioles is impaired during nitric oxide
      and cyclo-oxygenase inhibition and in diabetic patients without retinopathy.
AB  - Occlusion of retinal vessels leads to retinal ischaemia and hypoxia, which
      induces vasodilatation in adjacent retinal areas in order to normalize retinal
      oxygenation. Previous studies have shown that NO and COX products are involved in
      hypoxia-induced dilatation of retinal arterioles in vitro and in vivo, and that
      this response is disturbed in patients with diabetes mellitus. However, it is
      unknown to what extent post-hypoxic recovery of the diameter of retinal
      arterioles depends on NO and COX products in normal persons and in diabetic
      patients. The Dynamic Vessel Analyzer (DVA) was used to study the post-hypoxic
      diameter changes of larger retinal vessels in 20 normal persons, 20 diabetic
      patients without diabetic retinopathy, and in 18 patients with diabetic
      maculopathy before and after inhibition of the synthesis of nitric oxide and COX
      products. In normal persons, the arterioles had re-constricted (p > 0.99) 2
      minutes after termination of hypoxia in the absence of antagonists, but not after
      treatment with L-NMMA and diclofenac (p < 0.01 for all comparisons). In diabetic
      patients without retinopathy, the arterioles showed no diameter changes after
      termination of hypoxia during any of the interventions. In patients with diabetic
      maculopathy hypoxia had not dilated retinal arterioles (p > 0.1 for all
      comparisons) to allow the study of re-constriction. In all groups, the dilatation
      of venules remained significantly increased during the post-hypoxic observation
      period, both in the absence and in the presence of L-NMMA and diclofenac.Post
      hypoxic constriction of retinal arterioles depends on NO and COX products, and is
      impaired in diabetic patients before the development of retinopathy. This
      disturbance may contribute to the development of diabetic retinopathy, and should
      be the target of future interventional studies aimed at preventing and treating
      the disease.ClinicalTrials.gov identifier: NCT01689090.

PMID- 28752371
TI  - Retinal dystrophy and subretinal drusenoid deposits in female choroideremia
      carriers.
AB  - PURPOSE: To describe clinical and molecular characteristics in a group of Italian
      female choroideremia (CHM) carriers and report fundus patterns. METHODS: We
      retrospectively studied 11 female carriers belonging to six CHM families examined
      at the Regional Reference Center for Hereditary Retinal Degenerations at the Eye
      Clinic in Florence. We took into consideration patients with a comprehensive
      ophthalmological examination, fundus photography, optical coherence tomography
      (OCT), full field electro-retinography (ERG), and visual field (VF). All patients
      were screened for mutations of the CHM gene. RESULTS: Fundus examination revealed
      retinal abnormalities in all female carriers (11/11) in the study; in particular
      four fundus patterns were identified: pattern A (RPE dystrophy involving only the
      peripheral retina), pattern B (RPE dystrophy involving the peripheral retina and
      the posterior pole with small hypo-pigmented RPE areas), pattern C (RPE dystrophy
      involving the peripheral retina and the posterior pole with small yellowish well
      defined dots), and pattern D (RPE dystrophy involving the peripheral retina and
      the posterior pole with large hypo-pigmented RPE areas and well-defined yellowish
      dots). Pattern D was characterized by widespread macular subretinal drusenoid
      deposits (SDD). Half of the observed mutations were novel mutations. A genotype
      phenotype correlation was not identified. CONCLUSIONS: Retinal dystrophy and SDD
      were detected in our female CHM carriers, and fundus patterns have been described
      in this study. The recognition of specific fundoscopic patterns may permit a
      correct diagnosis, an appropriate molecular investigation and genetic counseling.

PMID- 28752372
TI  - The Cutaneous Spectrum of Lupus Erythematosus.
AB  - Systemic lupus erythematosus is a complex autoimmune disease with a wide spectrum
      of clinical and immunopathological features. Cutaneous and articular
      manifestations are the most common signs in patients with systemic lupus
      erythematosus. We here review the pathogenesis and the new classification of
      cutaneous lupus erythemathosus with a discussion of the significance of the
      various cutaneous signs. The lesions are classified according to the level of the
      cellular infiltrate and tissue damage in the epidermis, dermis, and/or subcutis.
      Furthermore, cutaneous lesions pointing to the presence of a thrombotic
      vasculopathy and those due to a distinct inflammatory, neutrophilic-mediated
      reaction pattern are highlighted. Particular attention will be given in
      describing the histology of skin manifestation. Treatment options for cutaneous
      lupus erythemathosus have increased with the introduction of new biological
      therapies. However, the majority of the patients still benefit from
      antimalarials, which remain the cornerstone of treatment. The evaluation and
      management of cutaneous lupus erythemathosus patients depend on the clinical
      findings and associated symptoms.

PMID- 28752374
TI  - Erratum to: Serelaxin in acute heart failure patients with and without atrial
      fibrillation: a secondary analysis of the RELAX-AHF trial.

PMID- 28752373
TI  - Skin Manifestations of Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, and
      Spondyloarthritides.
AB  - Extra-articular manifestations of rheumatoid arthritis, juvenile idiopathic
      arthritis, and various spondyloarthritides including psoriatic arthritis,
      ankylosing spondylitis, reactive arthritis, and inflammatory bowel disease
      associated spondyloarthritis often involve the skin and may occur before or after
      diagnosis of these rheumatic diseases. Cutaneous manifestations encompass a wide
      range of reactions that may have a notable negative impact not only on the
      physical but especially on the emotional and psychosocial well-being of these
      patients. Several cutaneous manifestations have been related to rheumatoid
      arthritis such as subcutaneous nodules including classical rheumatoid nodules,
      accelerated rheumatoid nodulosis, and rheumatoid nodulosis; vascular disorders
      like rheumatoid vasculitis, livedo racemosa, and Raynaud's phenomenon; and
      neutrophilic and/or granulomatous diseases like pyoderma gangrenosum, Sweet's
      syndrome, rheumatoid neutrophilic dermatitis, interstitial granulomatous
      dermatitis with arthritis, as well as palisaded neutrophilic and granulomatous
      dermatitis. In juvenile idiopathic arthritis, the main cutaneous manifestations
      include an evanescent rash, rheumatoid nodules, as well as plaque and guttate
      psoriasis. Plaque psoriasis is also the main skin disease involved in
      spondyloarthritides. Furthermore, other forms of psoriasis including guttate,
      inverse, erythrodermic, pustular, and particularly nail psoriasis may also occur.
      In addition, a variety of drug-induced skin reactions may also appear in these
      diseases. Early recognition and understanding of these different dermatologic
      manifestations together with an interdisciplinary approach are often needed to
      optimize management of these diseases.

PMID- 28752375
TI  - Biological and Physical Factors Involved in the Maturation of Arteriovenous
      Fistula for Hemodialysis.
AB  - One of the most important limitations of hemodialysis (HD) treatment is the
      vascular access (VA) that is used to connect the patient's blood vessels to the
      extracorporeal circulation. The arteriovenous fistula (AVF) obtained with native
      vessels is the VA of choice for the low incidence of infections and the long-term
      patency, but it is affected by high incidence of non-maturation or primary
      failure. Before use for cannulation, AVF must undergo vascular remodeling, with
      progressive increase in vessel diameter, to accommodate the increase in blood
      flow. A growing body of evidence indicates that AVF maturation is related to the
      response of endothelial cells to changes in blood flow and wall shear stress. In
      the present report we examine the experimental and clinical evidences on the
      mechanisms that play a role in vascular remodeling during AVF maturation. The
      physical and biological factors that develop upon arteriovenous surgical
      connection affect endothelial and smooth muscle cell function, as well as
      extracellular matrix remodeling. They can explain to a great extent the process
      of vascular remodeling and put more light on cellular mechanisms of vessel wall
      adaptation. The understanding of these phenomena, besides indicating the reasons
      for non-maturation and primary failure, may be fundamental in the future to
      ameliorate clinical outcomes of AVF creation, with a great impact on the clinical
      management of HD patients and their quality of life.

PMID- 28752376
TI  - Abdominal-pelvic scanning parameters revisited: a case for Z-axis reduction in
      patients with clinical suspicion for acute appendicitis.
AB  - PURPOSE: The purpose of this study was to determine if CT for appendicitis can be
      abbreviated to begin at the top of the L2 vertebral body level and still maintain
      the detection rate of appendicitis and other symptomatic pathology without
      omitting significant incidental findings. METHODS: Retrospective review of CT
      abdomen-pelvis exams for suspected appendicitis over a 5-month period was
      performed. The Z-axis scan length of the original full scans and theoretical
      limited scans from the top of L2 were recorded and calculated. Images were
      reviewed for incidental findings above the L2 vertebral body level and
      categorized by severity per American College of Radiology (ACR) white paper
      guidelines. Final diagnoses based on imaging findings were also recorded.
      RESULTS: One hundred nineteen patients (46 males, 73 females, mean age 29 +/- 14)
      were included. Appendicitis was present in 26 cases (22%). Using a theoretical
      scan beginning at the top of the L2 vertebral body, none of the findings leading
      to diagnosis of appendicitis would have been missed. A total of 30 incidental
      findings were found above the L2 vertebral body. Per ACR white paper guidelines,
      26 of these findings did not require additional imaging follow-up. Additional
      follow-up imaging was recommended for 3 of the findings above L2, and 1 right
      adrenal metastasis was found above L2 in a patient with previously undiagnosed
      NSCLC. This patient coincidentally also had appendicitis. No symptomatic
      pathology would have been missed had the scans begun at the top of the L2
      vertebral body. Such an abbreviated scan would have resulted in a mean Z-axis
      reduction of 12.9 cm (30.3%). CONCLUSIONS: CT using abbreviated Z-axis scan
      length can reduce radiation dose and provide necessary imaging needed to diagnose
      appendicitis or other symptomatic pathology without omitting significant
      incidental findings.

PMID- 28752377
TI  - Is he important to me? Source memory advantage for personally relevant cheaters.
AB  - A popular assumption in evolutionary psychology claims that reciprocal altruism
      is supported by a cognitive module that helps individuals to detect and remember
      cheaters. Previous studies found a source memory advantage for faces of cheaters
      rather than faces of cooperators. The present study examines memory for social
      exchange relevant information. More precisely, faces were shown together with
      behavior descriptions of cheating, trustworthy and neutral behavior either high
      or low in relevance for a student population. A multinomial model was used to
      measure old-new discrimination, source memory, and guessing biases separately.
      The study showed a source memory advantage for cheaters high in relevance.
      However, source memory for trustworthy persons low and high in relevance was also
      enhanced. The results are in line with the assumption of a flexible mechanism
      that focuses on exchange-relevant information. A system that is able to take into
      account the relative significance of information may be more beneficial than a
      system focusing on every cheater independently of his or her relative importance.

PMID- 28752378
TI  - A safety mechanism for observational learning.
AB  - This empirical article presents the first evidence of a "safety mechanism" based
      on an observational-learning paradigm. It is accepted that during observational
      learning, a person can use different strategies to learn a motor skill, but it is
      unknown whether the learner is able to circumvent the encoding of an uncompleted
      observed skill. In this study, participants were tested in a dyadic protocol in
      which an observer watched a participant practicing two different motor sequences
      during a learning phase. During this phase, one of the two motor sequences was
      interrupted by a stop signal that precluded motor learning. The results of the
      subsequent retention test revealed that both groups learned the two motor
      sequences, but only the physical practice group showed worse performance for the
      interrupted sequence. The observers were consequently able to use a safety
      strategy to learn both sequences equally. Our findings are discussed in light of
      the implications of the action observation network for sequence learning and the
      cognitive mechanisms of error-based observation.

PMID- 28752379
TI  - A Bayesian perspective on Likert scales and central tendency.
AB  - The central tendency bias is a robust finding in data from experiments using
      Likert scales to elicit responses. The present paper offers a Bayesian
      perspective on this bias, explaining it as a natural outcome of how participants
      provide point estimates of probability distributions over the items on a Likert
      scale. Two studies are reported that support this Bayesian explanation.

PMID- 28752380
TI  - Comparison of Banded Versus Non-banded Roux-en-Y Gastric Bypass: a Series of 1150
      Patients at a Single Institution.
AB  - BACKGROUND: Variations have been proposed in order to improve weight loss and
      decrease complication profiles in Roux-en-Y gastric bypass (RYGB) patients. We
      previously reported a preliminary result of pericardial patch ring RYGB. We aim
      to report a detailed result of banded RYGB by comparing these patients to non
      banded RYGB patients with larger case number and longer follow-up. MATERIAL AND
      METHODS: A retrospective chart review was performed in 543 banded RYGB and 607
      non-banded RYGB patients who underwent laparoscopic RYGB between January 2009 and
      December 2014. RESULTS: Thirty-day readmission rate was 3.1% (n = 16) in the
      banded group and 3.8% (n = 23) in the non-banded group. Thirty-day reoperation
      rate was 1.5% (n = 8) in the banded group and 1.6% (n = 10) in the non-banded
      group. Two mortalities occurred after a mesenteric venous thrombosis and an
      intracranial hemorrhage in the non-banded group. The differences in 30-day
      readmission and reoperation rates were not statistically significant between the
      two groups. Mean percentage of excess BMI loss (%EBMIL) dating from the time of
      RYGB was 53.1, 72.5, 76.5, 78.8, and 73.3% in the banded group, and 51.5, 73.5,
      78.8, 79.0, and 74.8% in the non-banded group at 6, 12, 18, 24, and 36 months,
      respectively, adjusted for preoperative BMI. The differences in %EBMIL were not
      significant at any follow-up points between the two groups. CONCLUSIONS: Banded
      laparoscopic RYGB with a pericardial patch may not demonstrate a significant
      additional weight loss or prevent future weight regain. We were not able to
      demonstrate a clear advantage of banded RYGB over non-banded RYGB.

PMID- 28752382
TI  - GLYCO 24 : XXIV International Symposium on Glycoconjugates.

PMID- 28752381
TI  - Erratum to: Histopathological Changes in Laparoscopic Sleeve Gastrectomy
      Specimens: Prevalence, Risk Factors, and Value of Routine Histopathologic
      Examination.

PMID- 28752383
TI  - Construction and functional characterization of truncated versions of recombinant
      keratanase II from Bacillus circulans.
AB  - There is a need for degradative enzymes in the study of glycosaminoglycans. Many
      of these enzymes are currently available either in their natural or recombinant
      forms. Unfortunately, progress in structure-activity studies of keratan sulfate
      (KS) have been impeded by the lack of a commercially available endo-beta-N
      acetylglucosaminidase, keratantase II. The current study uses a recently
      published sequence of a highly thermostable keratanase II identified in Bacillus
      circulans to clone and express a series of truncation mutants in Escherichia coli
      BL21. The resulting truncated forms of keratanase II exhibit activity and
      excellent storage and thermal stability making these useful tools for
      glycobiology research.

PMID- 28752384
TI  - Combining Two Methods of Global Sensitivity Analysis to Investigate MRSA Nasal
      Carriage Model.
AB  - We apply two different sensitivity techniques to a model of bacterial
      colonization of the anterior nares to better understand the dynamics of
      Staphylococcus aureus nasal carriage. Specifically, we use partial rank
      correlation coefficients to investigate sensitivity as a function of time and
      identify a reduced model with fewer than half of the parameters of the full
      model. The reduced model is used for the calculation of Sobol' indices to
      identify interacting parameters by their additional effects indices.
      Additionally, we found that the model captures an interesting characteristic of
      the biological phenomenon related to the initial population size of the
      infection; only two parameters had any significant additional effects, and these
      parameters have biological evidence suggesting they are connected but not yet
      completely understood. Sensitivity is often applied to elucidate model
      robustness, but we show that combining sensitivity measures can lead to
      synergistic insight into both model and biological structures.

PMID- 28752385
TI  - The population-based prevalence of albuminuria in children.
AB  - OBJECTIVES: To determine the population-based prevalence of albuminuria in
      Australian children and validate any negative correlation with body mass index
      (BMI). METHODS: Data from the Australian Health Survey 2011-2013 were used. This
      is a large-scale survey of the health of the Australian population, conducted by
      the Australian Bureau of Statistics, and uses a stratified, multistage area
      design with replicate weights attached to observations to allow for the
      derivation of accurate population estimates. We considered children aged 5-18
      years, and defined albuminuria as an albumin-to-creatinine ratio (ACR) >30 mg/g
      (3.4 mg/mmol). RESULTS: A total of 975 children provided urine samples for
      determination of ACR. The prevalence of albuminuria was 10.2% for males (95%
      confidence interval [CI] 6.1-14.2) and 15.5% for females (95% CI 10.7-20.3).
      After adjusting for age and gender, the odds ratio for albuminuria associated
      with being overweight or obese was 0.34 (95% CI 0.15-0.75). This relationship
      also held for waist-to-height ratio, where the adjusted odds ratio for each 0.1
      increase was 0.46 (95% CI 0.26-0.82). CONCLUSIONS: Albuminuria, using a
      measurement suitable for population-based and clinical screening, occurs in 12.8%
      of school-aged Australian children, and is less common in overweight and obese
      children.

PMID- 28752386
TI  - Glycolate oxidase deficiency in a patient with congenital hyperinsulinism and
      unexplained hyperoxaluria.
AB  - BACKGROUND: A baby girl was born at 39 weeks gestation to consanguineous Asian
      parents. From day 1 of life she had severe hypoglycaemia with an inappropriately
      elevated insulin concentration consistent with congenital hyperinsulinism (CHI),
      confirmed by the finding of a homozygous mutation in ABCC8 (encoding the
      sulfonylurea receptor 1). CASE DIAGNOSIS/TREATMENT: Urine organic acid analysis
      showed an incidentally elevated excretion of glycolate. Whilst this was unlikely
      to contribute to the hypoglycaemia, hyperglycolic aciduria is a known feature of
      primary hyperoxaluria type 1 (PH1); therefore oxalate was also measured in urine
      and found to be elevated. Sequence analysis of the genes involved in PH1 and also
      the two other known forms of primary hyperoxaluria revealed no pathological
      variants. PH1 was definitively excluded by enzyme activity analysis on a liver
      biopsy, which confirmed normal glyoxylate aminotransferase (AGT) activity and
      positive AGT immunoreactivity. Glycolate oxidase (GO) deficiency was considered,
      and thus gene sequencing of HAO1, which encodes GO, was performed. A homozygous
      change (c.493G>T p.(Gly165Cys)) was found in exon 3 of HAO1, predicted to be
      deleterious to protein function. Further analysis of the liver biopsy
      demonstrated absent GO enzyme activity, confirming GO deficiency in this case.
      CONCLUSIONS: The results lead to the conclusion that this baby has two unrelated
      autosomal recessive conditions, CHI and GO deficiency, and also hyperoxaluria of
      unknown aetiology. Deficiency of GO is a very rare disorder with only two
      previously published cases. It is considered to be an essentially benign inborn
      error of metabolism. The present case is unique in that GO deficiency is
      associated with persistent hyperoxaluria.

PMID- 28752387
TI  - Vitamin and trace element deficiencies in the pediatric dialysis patient.
AB  - Pediatric dialysis patients are at risk of nutritional illness secondary to
      deficiencies in water-soluble vitamins and trace elements. Unlike 25-OH vitamin
      D, most other vitamins and trace elements are not routinely monitored in the
      blood and, consequently, the detection of any deficiency may not occur until
      significant complications develop. Causes of vitamin and trace element deficiency
      in patients on maintenance dialysis patient are multifactorial, ranging from
      diminished nutritional intake to altered metabolism as well as dialysate-driven
      losses of water-soluble vitamins and select trace elements. In this review we
      summarize the nutritional sources of key water-soluble vitamins and trace
      elements with a focus on the biological roles and clinical manifestations of
      their respective deficiency to augment awareness of potential nutritional illness
      in pediatric patients receiving maintenance dialysis. The limited pediatric data
      on the topic of clearance of water-soluble vitamins and trace elements by
      individual dialysis modality are reviewed, including a brief discussion on
      clearance of water-soluble vitamins and trace elements with continuous renal
      replacement therapy.

PMID- 28752388
TI  - [Color vision in animals : From color blind seals to tetrachromatic vision in
      birds].
AB  - BACKGROUND: The colors in which we see an object are not only dependent on the
      spectral composition of the reflected light but also represent an interpretation
      by our eyes and the trichromatic visual system. OBJECTIVE: How do animals of
      other species see the world? RESULTS: The majority of mammals do not have three
      but only two types of cones and therefore have dichromatic color vision. Marine
      mammals and some nocturnally active mammals even have only one type of cone and
      are completely color blind. In contrast, birds as well as many fish and reptiles
      see in the world in more color hues and with four types of cones. Many
      vertebrates, insects and crustaceans can see not only the spectrum perceived by
      us but also ultraviolet radiation as light. CONCLUSION: In order to understand
      how animals of other species see the world, their visual systems must be
      understood and the animals must be tested in behavioral investigations.

PMID- 28752389
TI  - A comparative analysis of child passenger restraint use in China and the United
      States.
AB  - BACKGROUND: Few published studies have examined child passenger safety practices
      across countries. This study compared the prevalence and associated factors of
      child passenger restraint use among children, aged 0 to 17 in the state of Iowa
      in the United States, and the city of Shantou in China. METHODS: Child restraint
      use observations were conducted in Iowa and in Shantou in 2012, respectively,
      among child passengers. Observations in Iowa were conducted at randomly selected
      gas stations, while in Shantou observations were completed at randomly selected
      schools or medical clinics. Research observers approached the driver, observed
      restraint use, and collected brief survey data. RESULTS: A total of 3049 children
      from Iowa and 3333 children aged 0 to 17 years from Shantou were observed. For
      children aged 0 to 3 years, only 0.1% were compliantly restrained in Shantou as
      compared to 95.9% in Iowa. The proportion of children who were compliantly
      restrained in Shantou increased with age, but generally decreased with age in
      Iowa. In Shantou, 36.0% of children aged 0 to 3 were sitting in the front seat as
      compared to only 1.7% of children of the same age in Iowa. Driver seat belt use
      was significantly associated with child restraint in both Iowa and Shantou; the
      association was stronger in Iowa than Shantou for all age groups. CONCLUSIONS: A
      significantly higher prevalence of children who were not appropriately restrained
      was observed in Shantou than in Iowa. Our findings support the need of mandatory
      child safety restraint use legislation in China.

PMID- 28752390
TI  - PDGFRbeta-P2A-CreERT2 mice: a genetic tool to target pericytes in angiogenesis.
AB  - Pericytes are essential mural cells distinguished by their association with small
      caliber blood vessels and the presence of a basement membrane shared with
      endothelial cells. Pericyte interaction with the endothelium plays an important
      role in angiogenesis; however, very few tools are currently available that allow
      for the targeting of pericytes in mouse models, limiting our ability to
      understand their biology. We have generated a novel mouse line expressing
      tamoxifen-inducible Cre-recombinase under the control of the platelet-derived
      growth factor receptor beta promoter: PDGFRbeta-P2A-CreER T2 . We evaluated the
      expression of the PDGFRbeta-P2A-CreER T2 line by crossing it with fluorescent
      reporter lines and analyzed reporter signal in the angiogenic retina and brain at
      different time points after tamoxifen administration. Reporter lines showed
      labeling of NG2+, desmin+, PDGFRbeta+ perivascular cells in the retina and the
      brain, indicating successful targeting of pericytes; however, signal from
      reporter lines was also observed in a small subset of glial cells both in the
      retina and the brain. We also evaluated recombination in tumors and found
      efficient recombination in perivascular cells associated with tumor vasculature.
      As a proof of principle, we used our newly generated driver to delete Notch
      signaling in perivascular cells and observed a loss of smooth muscle cells in
      retinal arteries, consistent with previously published studies evaluating Notch3
      null mice. We conclude that the PDGFRbeta-P2A-CreER T2 line is a powerful new
      tool to target pericytes and will aid the field in gaining a deeper understanding
      of the role of these cells in physiological and pathological settings.

PMID- 28752391
TI  - Clinical dissection of thrombotic microangiopathy.
AB  - Differential treatment strategies are applied in thrombotic microangiopathy (TMA)
      according to the sub-classifications. Hence, it is worthwhile to overview
      clinical manifestations and outcomes of overall TMA patients according to sub
      classifications. We analyzed TMA patients whose serum lactate dehydrogenase
      levels >250 IU/L, with the presence of schistocytes in their peripheral blood
      smear, or with typical vascular pathologic abnormalities in their renal biopsy.
      We compared clinical manifestations including overall survival (OS) and renal
      survival according to TMA causes. A total of 117 TMA patients (57 primary and 60
      secondary TMA) were analyzed. Renal symptom was the most common manifestation in
      whole patients, while renal function at diagnosis was worst in pregnancy-related
      TMA group. Primary TMA patients had more frequent CNS symptom and hematologic
      manifestation compared to secondary TMAs. Among secondary TMAs, pregnancy- and
      HSCT-related TMA patients showed prevalent hemolytic features. During 150.2
      months of follow-up, 5-year OS rate was 64.8%. Poor prognostic factors included
      older age, combined hematologic and solid organ malignancies, lower hemoglobin
      levels, and lower serum albumin levels. There was no significant difference in OS
      between primary and secondary TMAs. Seventy-eight percent of patients experienced
      AKI during TMA. Five-year death-censored renal survival rate was poor with only
      69.2%. However, excellent renal outcome was observed in pregnancy-associated TMA.
      TMA showed various clinical manifestations according to their etiology. Notably,
      both OS and renal survival were poor regardless of their etiologies except
      pregnancy-associated TMA. Physicians should differentiate a variety of TMA
      categories and properly manage this complex disease entity.

PMID- 28752392
TI  - GATA2 gene analysis in several forms of hematological malignancies including
      familial aggregations.
AB  - The genetic predisposition to familial hematological malignancies has been
      previously reported highlighting inherited gene mutations. Several genes have
      been reported but genetic basis remains not well defined. In this study, we
      extended our investigation to a potential candidate GATA2 gene which was analyzed
      by direct sequencing in 119 cases including familial aggregations with a variety
      of hematological malignancies and sporadic acute leukemia belonging to Tunisian
      and French populations. We reported a deleterious p.Arg396Gln GATA2 mutation in
      one patient diagnosed with both sporadic acute myeloid leukemia (AML) and breast
      cancer. We also reported several GATA2 variations in familial cases. The absence
      of deleterious mutations in this large cohort of familial aggregations of
      hematological malignancies may strengthen the hypothesis that GATA2 mutations are
      an important predisposing factor, although as a secondary genetic event, required
      for the development of overt malignant disease.

PMID- 28752393
TI  - Sudden blindness as an initial manifestation of localized fusariosis in ethmoid
      sinus and optic nerve.

PMID- 28752394
TI  - A prolonged microscopic observation improves detection of underpopulated cells in
      peripheral blood smears.
AB  - We evaluated an extended time in the microscopic review in samples in which the
      potential clinical information could be increased with respect to those that
      could be achieved with the usual laboratory methodologies. We used samples
      containing nucleated red blood cells in a small amount and cytopenic samples. For
      these purposes for each peripheral blood smear, the timing of eye-count
      differential was increased up to 20 min, regardless of the final number of cells
      which could be counted. In addition, an automated system for digital analysis of
      peripheral blood smears was employed and the number of cells counted was brought
      up to 1000 leukocytes. In both manual and automatic light microscopy extended
      observation, we obtained more diagnostic information in respect to those with
      routine or standard methods. Both automated and manual increase systems of the
      timing for microscopic review are useful tools to find diagnostic information
      that otherwise would be lost using normal and standard procedures. So, these
      methods should be used especially when there is a higher pre-test probability for
      discovery of pathological cells.

PMID- 28752395
TI  - Neutrophil aggregation on the peripheral blood smear in a patient with cold
      agglutinin disease.

PMID- 28752396
TI  - Physico-chemical characterization of formulations containing endomorphin-2
      derivatives.
AB  - In this study semisolid formulations containing AcYPFF (N-acetyl-Tyr-Pro-Phe-Phe
      NH2) tetrapeptide were obtained and characterized in terms of rheology, stability
      by multiple light scattering and particle size distribution by laser diffraction.
      Additionally, the release studies of tetrapeptide from formulations obtained were
      performed. The influence of different factors such as semisolid and membrane type
      on tetrapeptide release rate was examined. The release experiments of
      tetrapeptide modified with palmitoyl group (PalmYPFF) were also carried out. The
      results proved that formulation type and its rheological properties strongly
      determined the permeation process of the tetrapeptide. The fastest release of
      tetrapeptide was observed from hydrogel that had the lowest viscosity. The
      kinetic data of tetrapeptide released from oil-in-water (o/w) and water-in-oil
      (w/o) emulsions prepared at elevated temperature showed good fit to the Higuchi
      equation, whereas when AcYPFF was released from oil-in-water (o/w) emulsion
      prepared with the addition of auto-emulsifier high linearity with Korsmeyer
      Peppas model was observed. While when tetrapeptide was released from Hydrogel the
      most suitable model was the first-order kinetics. It was suggested that mechanism
      that led to the release of tetrapeptide from all formulations was non-Fickian
      diffusion transport. The presence of palmitoyl group changed the solubility of
      tetrapeptide both in formulation and receptor fluid and thus the release rate of
      active compound was modified.

PMID- 28752400
TI  - Normal references of right ventricular strain values by two-dimensional strain
      echocardiography according to the age and gender.
AB  - Right ventricular (RV) strain values by 2-dimensional strain echocardiography
      (STE) can be used as objective markers of RV systolic function. However, there is
      little data about normal reference RV strain values according to age and gender.
      We measured normal RV strain values by STE. RV strain values were analyzed from
      the digitally stored echocardiographic images from NORMAL (Normal
      echOcardiogRaphic diMensions and functions in KoreAn popuLation) study for the
      measurement of normal echocardiographic values performed in 23 Korean university
      hospitals. We enrolled total 1003 healthy persons in the NORMAL study. Of them,
      we analyzed 2-dimensional RV strain values in 493 subjects (261 females, mean 47
      +/- 15 years old) only with echocardiographic images by GE machines. Their LV
      systolic and diastolic functions were normal. RV fractional area change was 48 +/
      6% and tricuspid annular plane systolic excursion was 23 +/- 3 mm. Total RV
      global longitudinal peak systolic strain (RVGLStotal) was -21.5 +/- 3.2%. Females
      had higher absolute RVGLStotal (-22.3 +/- 3.3 vs -20.7 +/- 2.9%, p < 0.001) than
      males. Younger (<50 years old) females had higher absolute RVGLStotal (-22.9 +/-
      3.2 vs -20.5 +/- 2.8%, p < 0.001) than age matched males. RVGLStotal in females
      gradually increased according to age (p for trend = 0.002) and becomes almost
      similar in age >=50 years. However, this trend was not seen in males (p for trend
      = 0.287), and younger males had similar RVGLStotal value to that of older males
      (age >=50 years, -20.5 +/- 2.8 vs -20.9 +/- 3.1%, p = 0.224). We calculated
      normal RVGLS values in normal population. Females have higher absolute strain
      values than males, especially in younger age groups (<50 years old).

PMID- 28752401
TI  - Muzi's Tension Free Primary Closure of Pilonidal Sinus Disease: Updates on Long
      Term Results on 514 Patients.
AB  - BACKGROUND: The aim of this study is to evaluate the long-term results of Muzi's
      tension free primary closure technique for pilonidal sinus disease (PSD), in
      terms of patients' discomfort and recurrence rate. METHODS: This study is a
      retrospective analysis of prospectively collected data. Five hundred fourteen
      patients were treated. Postoperative pain (assessed by a visual analog scale,
      VAS), complications, time needed to return to full-day activities, and recurrence
      rate were recorded. At 12, 22, and 54 months postoperative, patients'
      satisfaction was evaluated by a questionnaire scoring from 0 (not satisfied) to
      12 (greatly satisfied). RESULTS: The median operative time was 30 min. The
      overall postoperative complication rate was 2.52%. Median VAS score was 1. The
      mean of resumption to normal activity was 8.1 days. At median follow-up of 49
      months, recurrence rate was 0.4% (two patients). At 12 months' follow-up, the
      mean satisfaction score was 10.3 +/- 1.7. At 22 and 54 months' follow-up, the
      score was confirmed. CONCLUSIONS: Muzi's tension free primary closure technique
      has proved to be an effective treatment, showing in the long-term follow-up low
      recurrence rate and high degree of patient satisfaction. Therefore, we strongly
      recommend this technique for the treatment of PSD.

PMID- 28752402
TI  - Equipping the 8th Edition American Joint Committee on Cancer Staging for Gastric
      Cancer with the 15-Node Minimum: a Population-Based Study Using Recursive
      Partitioning Analysis.
AB  - BAKCGROUND: The recently proposed 8th American Joint Committee on Cancer (AJCC)
      staging for gastric cancer (GC) did not include the evaluated lymph node (ELN)
      count as a prognostic indicator. In this study, we performed recursive
      partitioning analysis (RPA) to objectively combine the 15-ELN threshold and 8th
      AJCC stage to refine the staging for GC. METHODS: We analyzed 19,018 patients
      with non-metastatic GC from the Surveillance, Epidemiology, and End Results
      database. The dataset was randomly divided into training and validation sets.
      RESULTS: For each 8th AJCC stage, survival was significantly better for patients
      with >=15 ELNs versus those with <15 ELNs (P < 0.001 for all). RPA divided non
      metastatic GC into seven stages: RPA-IA (8th AJCC IA with >=15 ELNs), RPA-IB (IA
      with <15 ELNs and IB/IIA with >=15 ELNs), RPA-IIA (IB with <15 ELNs and IIB with
      >=15 ELNs), RPA-IIB (IIA with <15 ELNs and IIIA with >=15 ELNs), RPA-IIIA (IIB
      with <15 ELNs), RPA-IIIB (IIIA with <15 ELNs and IIIB >=15 ELNs), and RPA-IIIC
      (IIIB with <15 ELNs and IIIC). The corresponding 5-year survival rates were 84.1,
      70.3, 52.8, 41.4, 32.9, 21.7, and 10.2%, respectively (P < 0.001 for all pairwise
      comparisons). The RPA staging outperformed the 8th AJCC staging in terms of
      discrimination and homogeneity among the SEER training and validation sets, as
      well as an independent Chinese cohort. CONCLUSION: By equipping the 8th AJCC
      stage with the 15-ELN threshold, the proposed RPA staging is superior to the 8th
      AJCC staging without overcomplicating.

PMID- 28752403
TI  - Common Bile Duct Duplication Type Va. A Rare but Important Anatomical Variation
      to Know.

PMID- 28752404
TI  - Preoperative Neutrophil to Lymphocyte Ratio and Lymphocyte to Monocyte Ratio are
      Prognostic Factors in Gastric Cancers Undergoing Surgery.
AB  - BACKGROUND: Cancer outcome is considered to result from the interplay of several
      factors, among which host inflammatory and immune status are deemed to play a
      significant role. The neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to
      monocyte ratio (LMR) have been profitably used as surrogate markers of host
      immunoinflammatory status and have also been shown to correlate with outcome in
      several human tumors. However, only a few studies on these biomarkers have been
      performed in gastric cancer patients, yielding conflicting results. METHODS: Data
      were retrieved from a prospective institutional database. Overall survival (OS)
      of 401 patients undergoing surgery for gastric cancer between January 2000 and
      June 2015 as well as disease-free survival (DFS) rates in 297 radically resected
      patients were calculated. MaxStat analysis was used to select cutoff values for
      NLR and LMR. RESULTS: NLR and LMR did not significantly correlate with tumor
      stage. Patients with a high NLR and a low LMR experienced more tumor recurrences
      (p < 0.001) and had a higher hazard ratio (HR) for both OS (HR = 2.4 and HR =
      2.10; p < 0.001) and DFS (HR = 2.99 and HR = 2.46; p < 0.001) than low NLR and
      high LMR subjects. Both biomarkers were shown to independently predict OS (HR =
      1.65, p = 0.016; HR = 2.01, p = 0.002, respectively) and DFS (HR = 3.04, p =
      0.019; HR = 4.76, p = 0.002, respectively). A score system combining both
      biomarkers was found to significantly correlate with long-term results.
      CONCLUSIONS: A simple prognostic score including preoperative NLR and LMR can be
      used to easily predict outcome in gastric cancer patients undergoing surgery.

PMID- 28752405
TI  - Extended Lymphadenectomy Is Required for Incidental Gallbladder Cancer
      Independent of Cystic Duct Lymph Node Status.
AB  - BACKGROUND: We examined whether the incidental cystic duct nodal status predicts
      the status of the hepatoduodenal ligament (D1) or common hepatic artery, the
      pancreaticoduodenal and paraaortic lymph nodes (D2), and the overall prognosis
      and thus indicates whether an oncologic extended resection (OER) is required.
      METHODS: The study included patients who underwent OER for incidental gallbladder
      cancer (IGBC) during 1999-2015. Associations between a positive cystic duct node
      and D2 nodal status and disease-specific survival (DSS) were analyzed. RESULTS:
      One-hundred-eight-seven patients were included. Seventy-three patients (39%) had
      the incidental cystic duct node retrieved. Cystic duct node positivity was
      associated with positive D1 (odds ratio 5.2, p = 0.012) but not with D2. Among
      all patients, a positive cystic duct node was associated with worse DSS (hazard
      ratio [HR] 2.09). Patients without residual cancer at OER and positive incidental
      cystic duct node had similar DSS to patients with negative nodes 70 vs 60% (p =
      0.337). Positive D1 (HR 6.07) or positive D2 (HR 13.8) was predictive of worse
      DSS. CONCLUSIONS: Patients with no residual cancer at OER and regional disease
      limited to their incidental cystic duct node have similar DSS to pN0 patients.
      The status of the cystic duct node only predicts the status of hepatic pedicle
      nodes.

PMID- 28752406
TI  - How I Do It: Per-Oral Pyloromyotomy (POP).
AB  - INTRODUCTION: Several surgical treatments exist for treatment of gastroparesis,
      including gastric electrical stimulation, pyloroplasty, and gastrectomy. Division
      of the pylorus by means of endoscopy, Per-Oral Pyloromyotomy (POP), is a newer,
      endoluminal therapy that may offer a less invasive, interventional treatment
      option. METHODS: We describe and present a video of our step by step technique
      for POP using a lesser curvature approach. The following are technical steps to
      complete the POP procedure from the lesser curve approach. CONCLUSION: In our
      experience, these methods provide promising initial results with low operative
      risks, although long-term outcomes remain to be determined.

PMID- 28752407
TI  - Variation in the Volatile Profiles of Black and Manchurian Ash in Relation to
      Emerald Ash Borer Oviposition Preferences.
AB  - Emerald ash borer (EAB; Agrilus planipennis) is a devastating pest of ash
      (Fraxinus spp.) in its invaded range in North America. Its coevolved Asian hosts
      are more resistant and less preferred for oviposition than susceptible North
      American species. We compared EAB oviposition preferences and bark and canopy
      volatile organic compound (VOC) emissions of resistant Manchurian ash and
      susceptible black ash, and examined relationships between VOC profiles and
      oviposition. In the field, black ash was highly preferred for oviposition while
      no eggs were laid on Manchurian ash, and we found clear differences in the VOC
      profiles of Manchurian and black ash. We detected 78 compounds emitted from these
      species, including 16 compounds that elicited EAB antennal activity in prior
      studies. Four compounds were unique to black and 11 to Manchurian ash. Emission
      rates of 14 canopy and 19 bark volatiles varied among the two species, including
      four previously reported as antennally active. Specifically, 7-epi-sesquithujene
      (bark) emissions were greater from black ash, while beta-caryophyllene (canopy),
      linalool (bark), and alpha-cubebene (bark) were emitted at higher rates by
      Manchurian ash. No relationships were found between the emission rate of any
      single compound or group of compounds (e.g. monoterpenes) suggesting that
      preference may be based on complex profile combinations. This is the first study
      to directly compare VOCs of black and Manchurian ash as well as the first to
      examine bark- and canopy-specific VOCs. The unique bark and canopy VOC profiles
      of these two species implicates potentially important variation in VOCs between a
      closely related resistant and susceptible species that provides a foundation for
      future studies of host preferences of EAB.

PMID- 28752408
TI  - The NLRP3 Inflammasome: An Important Driver of Neuroinflammation in Hemorrhagic
      Stroke.
AB  - Hemorrhagic stroke is a devastating clinical event with no effective medical
      treatment. Neuroinflammation, which follows a hemorrhagic stroke, is an important
      element that involves both acute brain injury and subsequent brain
      rehabilitation. Therefore, delineating the key inflammatory mediators and
      deciphering their pathophysiological roles in hemorrhagic strokes is of great
      importance in the development of novel therapeutic targets for this disease. The
      NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a
      multi-protein complex that is localized within the cytoplasm. This NOD-like
      receptor orchestrates innate immune responses to pathogenic organisms and cell
      stress through the activation of caspase-1 and the maturation of the
      proinflammatory cytokines such as interleukin-1beta (IL-1beta) and IL-18.
      Mounting evidence has demonstrated that when the NLRP3 inflammasome is activated,
      it exerts harmful effects on brain tissue after a hemorrhagic stroke. This review
      article summarizes the current knowledge regarding the role and the underlying
      mechanisms of the NLRP3 inflammasome in the pathophysiological processes of
      hemorrhagic strokes. A better understanding of the function and regulation of the
      NLRP3 inflammasome in hemorrhagic strokes will provide clues for devising novel
      therapeutic strategies to fight this disease.

PMID- 28752409
TI  - [IL-1-blockade with Anakinra during pregnancy : Retrospective analysis of
      efficacy and safety in female patients with familial Mediterranean fever].
AB  - OBJECTIVE: To retrospectively assess and analyze the clinical efficacy and safety
      of off-label interleukin-1 (IL-1) blockade with anakinra during pregnancy of
      patients with familial Mediterranean fever (FMF). METHODS: Retrospective analysis
      of clinical and laboratory parameters making use of an electronic database
      system. Detailed descriptions of the genotype and phenotype of FMF are given and
      the course of the pregnancy and fetal development are reported. RESULTS: The data
      of three patients and a total of four pregnancies under treatedment with anakinra
      were analyzed. All patients were of Mediterranean origin, fulfilled the Tel
      Hashomer criteria for diagnosis of FMF and had a confirmed mutation in the MEFV
      gene. In all patients, treatment with anakinra was initiated due to an
      insufficient treatment response to colchicine. Anakinra led to a rapid response
      in all patients. In three pregnancies anakinra treatment was continued during the
      whole pregnancy, while in one pregnancy anakinra was started in the second
      trimester because of uncontrolled FMF activity. Fetal development was normal in
      all pregnancies. In two patients the fetuses were carried to term, while in one
      patient a primary cesarean section was carried out in week 33 because of an
      increased risk for complications. All children showed an unremarkable early
      childhood development without any signs of an existing disease. CONCLUSION: The
      data of our retrospective analysis suggest that IL-1-blockade by anakinra is an
      effective and safe treatment in pregnant women suffering from FMF, which can
      reliably prevent disease flares. In the four pregnancies presented the use of
      anakinra did not result in impaired fetal and (early) childhood development.

PMID- 28752410
TI  - Infections Up to 76 Days After Stroke Increase Disability and Death.
AB  - Early infection after stroke is associated with a poor outcome. We aimed to
      determine whether delayed infections (up to 76 days post-stroke) are associated
      with poor outcome at 90 days. Data came from the international Efficacy of Nitric
      Oxide Stroke (ENOS, ISRCTN99414122) trial. Post hoc data on infections were
      obtained from serious adverse events reports between 1 and 76 days following
      stroke in this large cohort of patients. Regression models accounting for
      baseline covariates were used to analyse fatalities and functional outcomes
      (modified Rankin Scale (mRS), Barthel Index, Euro-Qol-5D) at 90 days, in patients
      with infection compared to those without infection. Of 4011 patients, 242 (6.0%)
      developed one or more serious infections. Infections were associated with an
      increased risk of death (p < 0.001) and an increased likelihood of dependency
      (measured by mRS) compared to those of all other patients (p < 0.001). This
      remained when only surviving patients were analysed, indicating that the
      worsening of functional outcome is not due to mortality (p < 0.001). In addition,
      the timing of the infection after stroke did not alter its detrimental
      association with fatality (p = 0.14) or functional outcome (p = 0.47). In
      conclusion, severe post-stroke infections, whether occurring early or late after
      stroke, are associated with an increased risk of death and poorer functional
      outcome, independent of differences in baseline characteristics or treatment. Not
      only are strategies needed for reducing the risk of infection immediately after
      stroke, but also during the first 3 months following a stroke. This study is
      registered: ISRCTN registry, number ISRCTN99414122, ClinicalTrials.gov
      Identifier, NCT00989716.

PMID- 28752411
TI  - Alcohol Consumption and Aneurysmal Subarachnoid Hemorrhage.
AB  - Alcohol consumption may be a modifiable risk factor for rupture of intracranial
      aneurysms. Our aim is to evaluate the association between ruptured aneurysms and
      alcohol consumption, intensity, and cessation. The medical records of 4701
      patients with 6411 radiographically confirmed intracranial aneurysms diagnosed at
      the Brigham and Women's Hospital and Massachusetts General Hospital between 1990
      and 2016 were reviewed. Individuals were divided into cases with ruptured
      aneurysms and controls with unruptured aneurysms. Univariable and multivariable
      logistic regression analyses were performed to determine the association between
      alcohol consumption and rupture of intracranial aneurysms. In multivariable
      analysis, current alcohol use (OR 1.36, 95% CI 1.17-1.58) was associated with
      rupture status compared with never drinkers, whereas former alcohol use was not
      significant (OR 1.23, 95% CI 0.92-1.63). In addition, the number of alcoholic
      beverages per day among current alcohol users (OR 1.13, 95% CI 1.04-1.23) was
      significantly associated with rupture status, whereas alcohol use intensity was
      not significant among former users (OR 1.02, 95% CI 0.94-1.11). Current alcohol
      use and intensity are significantly associated with intracranial aneurysm
      rupture. However, this increased risk does not persist in former alcohol users,
      emphasizing the potential importance of alcohol cessation in patients harboring
      unruptured aneurysms.

PMID- 28752412
TI  - Oxytocin participates on the effects of vasoactive intestinal peptide on food
      intake and plasma parameters.
AB  - Vasoactive intestinal peptide (VIP) is a neurotransmitter with anorectic effect
      that acts in the hypothalamus to regulate food intake. Oxytocin is a neuropeptide
      produced in the hypothalamus that controls energy homeostasis and has an
      inhibitory role on food intake. Thus, the present study aims at verifying the
      role of oxytocin as a mediator of VIP on energy homeostasis. For this purpose,
      intracerebroventricular microinjection of oxytocin receptor antagonist
      (vasotocin, OVT) or vehicle (NaCl 0.9%) was carried out in male rats, and after
      15 min, VIP or saline was microinjected. After 15 min of the second
      microinjection, food intake was evaluated or euthanasia was undertaken for blood
      collection. There was a reduction on food intake after VIP microinjection and the
      pretreatment with OVT partially reversed this effect. Hyperglycemia was observed
      after VIP microinjection, and pretreatment with OVT partially blocked this
      effect. Plasma corticosterone concentration was significantly increased after VIP
      or OVT. Plasma levels of free fatty acids were decreased by VIP, but not when VIP
      was microinjected after OVT. Thus, OVT partially reversed VIP-induced hypophagia
      and changes on plasma metabolic parameters, suggesting a role for oxytocin as a
      mediator of VIP effects on energy homeostasis.

PMID- 28752413
TI  - Punctuated evolution of viscid silk in spider orb webs supported by mechanical
      behavior of wet cribellate silk.
AB  - The origin of viscid capture silk in orb webs, from cribellate silk-spinning
      ancestors, is a key innovation correlated with significant diversification of web
      building spiders. Ancestral cribellate silk consists of dry nanofibrils
      surrounding a stiff, axial fiber that adheres to prey through van der Waals
      interactions, capillary forces, and physical entanglement. In contrast, viscid
      silk uses chemically adhesive aqueous glue coated onto a highly compliant and
      extensible flagelliform core silk. The extensibility of the flagelliform fiber
      accounts for half of the total work of adhesion for viscid silk and is enabled by
      water in the aqueous coating. Recent cDNA libraries revealed the expression of
      flagelliform silk proteins in cribellate orb-weaving spiders. We hypothesized
      that the presence of flagelliform proteins in cribellate silk could have allowed
      for a gradual shift in mechanical performance of cribellate axial silk, whose
      effect was masked by the dry nature of its adhesive. We measured supercontraction
      and mechanical performance of cribellate axial silk, in wet and dry states, for
      two species of cribellate orb web-weaving spiders to see if water enabled
      flagelliform silk-like performance. We found that compliance and extensibility of
      wet cribellate silk increased compared to dry state as expected. However, when
      compared to other silk types, the response to water was more similar to other web
      silks, like major and minor ampullate silk, than to viscid silk. These findings
      support the punctuated evolution of viscid silk mechanical performance.

PMID- 28752414
TI  - Effectiveness of Mindfulness- and Relaxation-Based eHealth Interventions for
      Patients with Medical Conditions: a Systematic Review and Synthesis.
AB  - PURPOSE: This systematic review aims to summarize eHealth studies with
      mindfulness- and relaxation-based interventions for medical conditions and to
      determine whether eHealth interventions have positive effects on health. METHOD:
      A comprehensive search of five databases was conducted for all available studies
      from 1990 to 2015. Studies were included if the intervention was mainly
      technology delivered and included a mindfulness- or relaxation-based intervention
      strategy and if patients with a medical condition were treated. Treatment effects
      were summarized for different outcomes. RESULTS: A total of 2383 records were
      identified, of which 17 studies with 1855 patients were included in this
      systematic review. These studies were conducted in patients with irritable bowel
      syndrome, chronic fatigue syndrome, cancer, chronic pain, surgery, and
      hypertension. All but one study were delivered online through a web-based
      platform; one study delivered the intervention with iPods. The studies indicate
      that mindfulness- and relaxation-based eHealth interventions can have positive
      effects on patients' general health and psychological well-being. No effects were
      found for stress or mindfulness. Only five studies reported economic analyses of
      eHealth interventions without any clear conclusion. CONCLUSION: There is some
      evidence that mindfulness- and relaxation-based eHealth interventions for medical
      conditions can have positive effects on health outcomes. Therefore, such
      interventions might be a useful addition to standard medical care. No app studies
      were retrieved, even though a vast number of smartphone apps exist which aim at
      increasing users' health. Therefore, more studies investigating those health apps
      are needed.

PMID- 28752415
TI  - Computational study of Simultaneous synthesis of optically active (RS)-1,2,4
      butanetriol trinitrate (BTTN).
AB  - In respective water or ethanol polarizable continuum cavity environments,
      simultaneous aldol condensation was performed using density functional theory
      (DFT) computational method to model the synthesis of optically active (RS)-1,2,4
      butanetriol trinitrate (BTTN). The results of reaction energy barrier analysis
      suggested feasible routes with lower activation energies to obtain either the (R)
      or (S)-configuration product in ethanolic solution. In addition, local analysis
      of average inter-particulate distances of reaction species revealed that a
      stronger inter-particulate interaction accompanied a shorter average distance in
      the ethanol system. The stabilization effect also indicated that related
      syntheses would be able to proceed in ethanol. Furthermore, relative to the
      production of (R)-BTTN, a lower overall energy of 425.3 kJ/mol was required for
      the synthesis of (S)-BTTN. Through analysis of the effects of temperature on the
      reaction rates of individual parallel stages of (R)- and (S)-species synthesis,
      it was simple to adjust the reaction temperature accordingly to differentiate
      between relative rates in order to obtain a product of a specific configuration.
      Graphical abstract ?.

PMID- 28752416
TI  - The particularity of dignity: relational engagement in care at the end of life.
AB  - This paper articulates dignity as relational engagement in concrete care
      situations. Dignity is often understood as an abstract principle that represents
      inherent worth of all human beings. In actual care practices, this principle has
      to be substantiated in order to gain meaning and inform care activities. We
      describe three exemplary substantiations of the principle of dignity in care: as
      a state or characteristic of a situation; as a way to differentiate between socio
      cultural positions; or as personal meaning. We continue our analysis by
      presenting cases on dignity in care related to us in focus groups with medical
      professionals. Our empirical ethical lens is in this paper is to analyse, not the
      meaning of dignity, but the way in which it emerges in practices where it is
      pursued, within relationships between people, technologies, places, regulations,
      and the values cherished by or embedded in them. We show that professional
      caregivers recognize in the dignity of the person they care for their own
      dignity; giving up on the one implies no less than giving up on the other. This
      'mirrored experience' of dignity expresses itself in professional's engagement
      with the situation. The value of this engagement, we argue, lies not primarily in
      realizing the particular content of the values at stake. We point to the
      importance of engagement itself, even if the values engaged with cannot be
      realized to the full, and even if competing versions of dignity are at stake
      simultaneously. In this way the caregivers provide us with interesting examples
      of moral actorship in situations of conflicting values.

PMID- 28752417
TI  - Metformin Alleviated the Neuronal Oxidative Stress in Hippocampus of Rats under
      Single Prolonged Stress.
AB  - In an animal model of post-traumatic stress disorder (PTSD), our previous studies
      showed mitochondrial stress-induced apoptosis in the hippocampus. Metformin, the
      most commonly prescribed anti-diabetic drug, exerts its effects through 5'
      adenosine monophosphate-activated protein kinase (AMPK) activation. It was shown
      that a neuroprotective role was gradually established against stroke, spinal cord
      injury and Parkinson's disease. The aim of this study was to explore the role of
      the AMPK pathway in neuronal apoptosis in the hippocampus using a rat model of
      PTSD. The model PTSD rats received acute exposure to prolonged stress (single
      prolonged stress, SPS), followed by examination of the effects of genes and/or
      proteins related to the AMPK and oxidative stress pathways in the hippocampus
      with or without metformin preconditioning. The results indicated that the level
      of phosphorylated AMPK was markedly increased after SPS. Metformin protected the
      hippocampus as evidenced by abolishing down-regulation of the AMPK pathway and up
      regulating expression of oxidative stress-related genes. These results indicated
      that metformin attenuated oxidative stress in the hippocampus in rats under SPS.
      AMPK pathway activation may be a novel therapeutic protocol for PTSD patients.

PMID- 28752418
TI  - The effect of perinatal fish oil supplementation on neurodevelopment and growth
      of infants: a randomized controlled trial.
AB  - INTRODUCTION: Long-chain polyunsaturated fatty acids, the most abundant fatty
      acids in the brain, are essential for the growth and development of the brain and
      the retina. OBJECTIVE: To evaluate the effect of fish oil supplementation on the
      development (primary outcome) and growth of 4- and 6-month-old infants. METHODS:
      In this triple-blind randomized controlled trial, 150 pregnant women aged 18-35
      years, who were referred to healthcare centres of Tabriz-Iran, were randomly
      allocated into two groups. One group of women consumed fish oil supplementation
      (containing 120 mg docosahexaenoic acid and 180 mg eicosapentaenoic acid) daily,
      while the other consumed a placebo from the 20th week of pregnancy till 30 days
      after childbirth in a parallel design by a computer-generated block randomization
      scheme. The neurodevelopment of infants was the primary outcome; it was assessed
      using the ages and stages questionnaire (ASQ) at 4- and a-6 months of age. The
      growth of these infants was measured using weight, length and head circumference.
      The participants, the caregivers, and those assessing the outcomes were blind to
      the group assignment. RESULTS: Only one woman in the placebo group discontinued
      the intervention because of persistent severe nausea. All 75 neonates aged 4- and
      a-6 months in the fish oil supplementation group, along with 73 and 71 neonates
      aged 4 and 6 months, respectively in the placebo group, were followed and
      analysed. Although the mean scores of neurodevelopment at the end of 4 and 6
      months were higher in the supplemented group than in the placebo group in each
      ASQ domain, a statistically significant difference was observed only in the
      communication domain at the 4th month (adjusted mean difference 2.63; 95%
      confidence interval 0.36-4.89). There was no significant difference in weight,
      length, or head circumference between the two groups of infants aged 4 and 6
      months (P >= 0.05). CONCLUSION: Based on the results, perinatal fish oil
      supplementation is beneficial for the communication domain of neurodevelopment of
      4-month-old infants. The study results relating to the supplementation effect on
      other domains are inconclusive. There ought to be further studies with up-to-date
      lipidomic analysis to find biochemical correlate compared to an intervention and
      developmental finding.

PMID- 28752419
TI  - Regional Variability of Repeat Esophagogastroduodenoscopy Use in the National
      Veteran Population.
AB  - BACKGROUND: Esophagogastroduodenoscopy (EGD) procedures are performed frequently
      to evaluate gastrointestinal disease and symptoms. AIM: To determine regional
      practice variability of repeat EGDs in a national population. METHODS: The study
      sample included US Veterans with an outpatient index EGD from 1/1/2008 to
      12/2010. We determined risk of repeat endoscopy from 1/2008 to 10/1/2014. A
      logistic regression model was used to assess the association between the odds of
      repeated EGD and patient demographics, ICD diagnostic codes, and geographic
      region. Multivariable logistic regression was performed to obtain the adjusted
      odds ratio and predicted probabilities of repeat EGDs by region. RESULTS: A total
      of 202,086 patients had an index endoscopy from 1/2008 to 12/2010. Unique
      patients with an index endoscopy were predominantly male (93.2%), white (72.8%),
      and on average 61 years. A total of 58,469 patients (28.9%) had one or more
      repeat EGDs, accounting for 103,253 repeat procedures through 10/2014. ICD-9-CM
      codes associated with increased risk of repeat procedures were Barrett's
      esophagus (OR 3.6, 95% CI 3.5-3.7), dysphagia (OR 1.3, 95% CI 1.2-1.3), ulcer (OR
      1.3, 95% CI 2.2-2.4), stricture (OR 1.8, 95% CI 1.7-1.9), and esophageal varices
      (OR 2.8, 95% CI 2.7-3.0). There was a significant difference in the probability
      of repeat EGD by VA region, with the Midwest region having the highest
      probability (31.2%) and Southeast the lowest probability (27.3%). This difference
      would account for 400 more EGD procedures per 10,000 Veterans, after adjusting
      for patient demographics and diagnosis codes. CONCLUSIONS: Regional practice
      variability accounts for a substantial volume of repeat EGD procedures,
      regardless of patient characteristics and associated diagnoses.

PMID- 28752420
TI  - Alzheimer's disease CSF biomarkers: clinical indications and rational use.
AB  - This review focusses on the validation and standardization of Alzheimer's disease
      (AD) cerebrospinal fluid (CSF) biomarkers, as well as on the current clinical
      indications and rational use of CSF biomarkers in daily clinical practice. The
      validated AD CSF biomarkers, Abeta1-42, T-tau, and P-tau181, have an added value
      in the (differential) diagnosis of AD and related disorders, including mixed
      pathologies, atypical presentations, and in case of ambiguous clinical dementia
      diagnosis. CSF biomarkers should not be routinely used in the diagnostic work-up
      of dementia and cannot be used to diagnose non-AD dementias. In cognitively
      healthy subjects, CSF biomarkers can only be applied for research purposes, e.g.,
      to identify pre-clinical AD in the context of clinical trials with potentially
      disease-modifying drugs. Therefore, biomarker-based early diagnosis of AD offers
      great opportunities for preventive treatment development in the near future.

PMID- 28752421
TI  - Modeling a SI epidemic with stochastic transmission: hyperbolic incidence rate.
AB  - In this paper a stochastic susceptible-infectious (SI) epidemic model is
      analysed, which is based on the model proposed by Roberts and Saha (Appl Math
      Lett 12: 37-41, 1999), considering a hyperbolic type nonlinear incidence rate.
      Assuming the proportion of infected population varies with time, our new model is
      described by an ordinary differential equation, which is analogous to the
      equation that describes the double Allee effect. The limit of the solution of
      this equation (deterministic model) is found when time tends to infinity. Then,
      the asymptotic behaviour of a stochastic fluctuation due to the environmental
      variation in the coefficient of disease transmission is studied. Thus a
      stochastic differential equation (SDE) is obtained and the existence of a unique
      solution is proved. Moreover, the SDE is analysed through the associated Fokker
      Planck equation to obtain the invariant measure when the proportion of the
      infected population reaches steady state. An explicit expression for invariant
      measure is found and we study some of its properties. The long time behaviour of
      deterministic and stochastic models are compared by simulations. According to our
      knowledge this incidence rate has not been previously used for this type of
      epidemic models.

PMID- 28752422
TI  - Regulation of Clock Genes by Adrenergic Receptor Signaling in Osteoblasts.
AB  - The clock system has been identified as one of the major mechanisms controlling
      cellular functions. Circadian clock gene oscillations also actively participate
      in the functions of various cell types including bone-related cells. Previous
      studies demonstrated that clock genes were expressed in bone tissue and also that
      their expression exhibited circadian rhythmicity. Recent findings have shown that
      sympathetic tone plays a central role in biological oscillations in bone.
      Adrenergic receptor (AR) signaling regulates the expression of clock genes in
      cancellous bone. Furthermore, alpha1-AR signaling in osteoblasts is known to
      negatively regulate the expression of bone morphogenetic protein-4 (Bmp4) by up
      regulating nuclear factor IL-3 (Nfil3)/e4 promoter-binding protein 4 (E4BP4). The
      ablation of alpha1B-AR signaling also increases the expression of the Bmp4 gene
      in bone. The findings of transient overexpression and siRNA experiments have
      supported the involvement of the transcription factor CCAAT/enhancer-binding
      protein delta (C/EBPdelta, Cebpd) in Nfil3 and Bmp4 expression in MC3T3-E1 cells.
      These findings suggest that the effects of Cebpd are due to the circadian
      regulation of Bmp4 expression, at least in part, by the up-regulated expression
      of the clock gene Nfil3 in response to alpha1B-AR signaling in osteoblasts.
      Therefore, AR signaling appears to modulate cellular functionality through the
      expression of clock genes that are circadian rhythm regulators in osteoblasts.
      The expression of clock genes regulated by the sympathetic nervous system and
      clock-controlled genes that affect bone metabolism are described herein.

PMID- 28752423
TI  - In Vitro Evaluation of the Probiotic and Safety Properties of Bacteriocinogenic
      and Non-Bacteriocinogenic Lactic Acid Bacteria from the Intestines of Nile
      Tilapia and Common Carp for Their Use as Probiotics in Aquaculture.
AB  - In this study, seven bacteriocinogenic and non-bacteriocinogenic LAB strains
      previously isolated from the intestines of Nile tilapia and common carp and that
      showed potent antibacterial activity against host-derived and non-host-derived
      fish pathogens were assayed for their probiotic and safety properties so as to
      select promising candidates for in vivo application as probiotic in aquaculture.
      All the strains were investigated for acid and bile tolerances, transit tolerance
      in simulated gastrointestinal conditions, for cell surface characteristics
      including hydrophobicity, co-aggregation and auto-aggregation, and for bile salt
      hydrolase activity. Moreover, haemolytic, gelatinase and biogenic amine-producing
      abilities were investigated for safety assessment. The strains were found to be
      tolerant at low pH (two strains at pH 2.0 and all the strains at pH 3.0). All of
      them could also survive in the presence of bile salts (0.3% oxgall) and in
      simulated gastric and intestinal juices conditions. Besides, three of them were
      found to harbour the gtf gene involved in pH and bile salt survival. The strains
      also showed remarkable cell surface characteristics, and 57.14% exhibited the
      ability to deconjugate bile salts. When assayed for their safety properties, the
      strains prove to be free from haemolytic activity, gelatinase activity and they
      could neither produce biogenic amines nor harbour the hdc gene. They did not also
      show antibiotic resistance, thus confirming to be safe for application as
      probiotics. Among them, Lactobacillus brevis 1BT and Lactobacillus plantarum 1KMT
      exhibited the best probiotic potentials, making them the most promising
      candidates.

PMID- 28752424
TI  - Factors associated with hernia recurrence after laparoscopic total
      extraperitoneal repair for inguinal hernia: a 2-year prospective cohort study.
AB  - BACKGROUND: Laparoscopic total extraperitoneal repair (TEP) of inguinal hernia
      has been associated with higher rates of recurrence compared to open methods. The
      aim of the present study was to determine independent risk factors for recurrence
      within 2 years after TEP. METHODS: This was a single-centre prospective cohort
      study with consecutive inclusion of patients undergoing inguinal hernia repair
      from 2010 to 2014. Systematic follow-up was conducted 6 months and 2 years
      postoperatively. Risk factors for recurrence after 2 years were analysed in
      univariate and multivariate analyses. RESULTS: A total of 1194 patients underwent
      TEP for inguinal or femoral hernia in the study period, of which 1047 were
      eligible for analyses. After 2 years, 56 (5.3%) patients had presented with
      recurrence. The following factors were associated with recurrence in univariate
      analyses: body mass index (BMI) >30 (HR 3.64; p = 0.011), medial vs. lateral
      hernia (HR 2.37; p = 0.004), repair of recurrent hernia vs. primary repair (HR
      2.12; p = 0.049), and length of stay >1 day (HR 1.77; p = 0.043). In multivariate
      analyses, factors independently associated with recurrence after 2 years were BMI
      >30 (HR 3.74; p = 0.026) and medial vs. lateral hernia (HR 2.39; p = 0.004).
      CONCLUSION: The recurrence rate after TEP is higher than reported after open
      hernia repair. Attempts to decrease the rate should be persuaded. Good surgical
      technique with precise dissection and correct placement of the mesh, especially
      in medial hernias and obese patients, may be key points to improve outcomes after
      TEP.

PMID- 28752425
TI  - Minimal modulation of the host immune response to SIS matrix implants by
      mesenchymal stem cells from the amniotic fluid.
AB  - PURPOSE: Surgical restoration of soft tissue defects often requires implantable
      devices. The clinical outcome of the surgery is determined by the properties
      inherent to the used matrix. Mesenchymal stem cells (MSC) modulate the immune
      processes after in vivo transplantation and their addition to matrices is
      associated with constructive remodeling. Herein we evaluate the potential of MSC
      derived from the amniotic fluid (AF-MSC), an interesting MSC source for cell
      therapeutic applications in the perinatal period, for immune modulation when
      added to a biomaterial. METHODS: We implant cell free small intestinal submucosa
      (SIS) or SIS seeded with AF-MSC at a density of 1 * 105/cm2 subcutaneously at the
      abdominal wall in immune competent rats. The host immune response is evaluated at
      3, 7 and 14 days postoperatively. RESULTS: The matrix-specific or cellular
      characteristics are not altered after 24 h of in vitro co-culture of SIS with AF
      MSC. The host immune response was not different between animals implanted with
      cell free or AF-MSC-seeded SIS in terms of cellular infiltration, vascularity,
      macrophage polarization or scaffold replacement. Profiling the mRNA expression
      level of inflammatory cytokines at the matrix interface shows a significant
      reduction in the expression of the pro-inflammatory marker Tnf-alpha and a trend
      towards lower iNos expression upon AF-MSC-seeding of the SIS matrix. Anti
      inflammatory marker expression does not alter upon cell seeding of matrix
      implants. CONCLUSION: We conclude that SIS is a suitable substrate for in vitro
      culture of AF-MSC and fibroblasts. AF-MSC addition to SIS does not significantly
      modulate the host immune response after subcutaneous implantation in rats.

PMID- 28752426
TI  - Erratum to: Functional Viability: Measurement of Synaptic Vesicle Pool Sizes.

PMID- 28752427
TI  - A Novel Lateral Approach to the Assessment of Vocal Cord Movement by
      Ultrasonography.
AB  - BACKGROUND: Ultrasonography is a non-invasive technique that is commonly used by
      endocrinologists and endocrine surgeons to examine the thyroid region and could
      be useful for the assessment of vocal cord movement by these specialists.
      However, previous studies reported a low rate of successful visualization of
      vocal cord movement by ultrasonography. To address this issue, we devised a novel
      ultrasonographic procedure for assessing vocal cord movement indirectly by
      observing the arytenoid movement from a lateral view. METHODS: Subjects were 188
      individuals, including 23 patients with vocal cord paralysis and 13 with vocal
      cord paresis. We performed ultrasonographic assessment of vocal cord movement
      using two different procedures: the conventional middle transverse procedure and
      the novel lateral vertical procedure. RESULTS: The rate of visualization of vocal
      cords with the middle transverse procedure was 70.2% and that of the arytenoid
      cartilage with the lateral vertical procedure was 98.4%. The lateral vertical
      procedure enabled visualization of all patients with vocal cord paresis/paralysis
      and detected all 23 patients with vocal paralysis; only one of 13 patients with
      vocal cord paresis was positively identified. The conventional procedure enabled
      visualization of 21 of 36 patients with vocal cord paresis/paralysis with high
      accuracy. There was no false-positive case in either procedure. CONCLUSION: The
      proposed lateral vertical procedure improved the rate of visualization of vocal
      cord movement by ultrasonography, suggesting that it is a useful technique to
      screen for vocal cord paralysis by ultrasonography.

PMID- 28752428
TI  - Laparoscopic Treatment in Children with Hydatid Cyst of the Liver.
AB  - BACKGROUND: There is no consensus on the surgical treatment of children with
      hydatid cyst of the liver (HCL). We evaluated the outcomes of laparoscopic and
      open surgery for childhood HCL. METHODS: We performed 81 open surgery and
      laparoscopic procedures in 37 (45.7%) boys and 44 (54.3%) girls with HCL (mean
      age 9.3 +/- 2.1 years) who were assigned to a main group (laparoscopy, n = 21)
      and a control group (open surgery, n = 60). Clinical assessments, surgical
      durations, complications, and postoperative outcomes were investigated. Cyst
      types in the two groups were I (Gharbi)/CE 1 (WHO-IWGE), 71.4 and 58.3%,
      respectively; II/CE 2, 19.1 and 25.0%, respectively; and III/CE 3, 9.5 and 16.7%,
      respectively. The parasitic hydatid cysts were located mostly in the right liver
      lobe in both the main and control groups (90.4 and 80.0%, respectively). RESULTS:
      Hospital stays were significantly (p < 0.05) longer in patients in the control
      group (12.1 +/- 1.5 vs. 5.6 +/- 2.2 days). Operation time was significantly (p <
      0.01) shorter for the main group (90.1 +/- 7.8 vs. 120.6 +/- 5.3 min). Local
      complications (residual cavity infection, biliary fistula) occurred in 21.6% of
      patients in the control group and 14.3% in the main group. Each was treated, and
      none recurred. There were no apparent systemic complications. CONCLUSIONS:
      Laparoscopic surgical treatment for children with HCL is safe in compliance with
      all classic open surgery principles. The laparoscopic technique offered a shorter
      duration of the surgical effects and markedly fewer postoperative complications.

PMID- 28752429
TI  - Short-Term Outcomes of Totally Laparoscopic Central Hepatectomy and Right
      Anterior Sectionectomy for Centrally Located Tumors: A Case-Matched Study with
      Propensity Score Matching.
AB  - BACKGROUND: Recent advances in technology and accumulation of surgical experience
      have expanded the indications for laparoscopic liver resection (LLR). However,
      compared to open liver resection (OLR), the feasibility of laparoscopic
      anatomical liver resection for centrally located tumor (CLT) has not been clearly
      established. The aim of our study was to assess the feasibility and safety of
      laparoscopic anatomical major liver resection for CLT. METHODS: From April 2011
      to March 2016, 20 cases of anatomical LLR and 86 cases of OLR for CLTs such as
      central hepatectomy (CH) and right anterior sectionectomy (RAS) were performed at
      a single institution. We performed one-to-one propensity score matching and
      analyzed short-term outcomes between the LLR (n = 20) and OLR (n = 20) groups.
      RESULTS: Among 20 cases in the LLR group, two cases underwent open conversion due
      to common bile duct injury and anatomical distortion, respectively. There were no
      statistically significant difference between the LLR and OLR groups regarding
      clamping time of the Pringle maneuver (p = 0.502), blood loss (p = 0.746),
      surgical margin (p = 0.198), or length of hospital stay (p = 0.110). However,
      surgical time was significantly longer in the LLR group than in the OLR group
      (388 vs 268 min; p < 0.001). There were no significant differences between the
      two groups with regard to morbidity rate or mean comprehensive complication index
      (p = 0.716 and p = 0.819, respectively). CONCLUSION: Total anatomical LLR can be
      performed safely in selected CLT patients by experienced surgeons. Laparoscopic
      CH or RAS appears feasible with non-inferior perioperative outcomes compared to
      OLR.

PMID- 28752430
TI  - Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro
      Pharmacokinetic Studies.
AB  - Investigation of the pharmacokinetics (PK) of a compound is of significant
      importance during the early stages of drug development, and therefore several in
      vitro systems are routinely employed for this purpose. However, the need for more
      physiologically realistic in vitro models has recently fueled the emerging field
      of tissue-engineered 3D cultures, also referred to as organs-on-chips, or
      microphysiological systems (MPSs). We have developed a novel fluidic platform
      that interconnects multiple MPSs, allowing PK studies in multi-organ in vitro
      systems along with the collection of high-content quantitative data. This
      platform was employed here to integrate a gut and a liver MPS together in
      continuous communication, and investigate simultaneously different PK processes
      taking place after oral drug administration in humans (e.g., intestinal
      permeability, hepatic metabolism). Measurement of tissue-specific phenotypic
      metrics indicated that gut and liver MPSs can be fluidically coupled with
      circulating common medium without compromising their functionality. The PK of
      diclofenac and hydrocortisone was investigated under different experimental
      perturbations, and results illustrate the robustness of this integrated system
      for quantitative PK studies. Mechanistic model-based analysis of the obtained
      data allowed the derivation of the intrinsic parameters (e.g., permeability,
      metabolic clearance) associated with the PK processes taking place in each MPS.
      Although these processes were not substantially affected by the gut-liver
      interaction, our results indicate that inter-MPS communication can have a
      modulating effect (hepatic metabolism upregulation). We envision that our
      integrative approach, which combines multi-cellular tissue models, multi-MPS
      platforms, and quantitative mechanistic modeling, will have broad applicability
      in pre-clinical drug development.

PMID- 28752432
TI  - Beta-blockers and perioperative outcomes in vascular surgery.

PMID- 28752431
TI  - Effects of epigallocatechin-3-gallate on systemic inflammation-induced cognitive
      dysfunction in aged rats.
AB  - PURPOSE: In this study, we examined the effects of epigallocatechin-3-gallate
      (EGCG), a green tea polyphenol, on sepsis-induced neurocognitive abnormity in
      aged rats. METHODS: Aged rats received an intraperitoneal (i.p.) injection of 5.0
      mg/kg lipopolysaccharide (LPS) or saline. Animals were further divided into three
      groups: control, low-dose EGCG (4.0 mg/kg), and high-dose EGCG (20 mg/kg). EGCG
      was i.p. injected at the same time, 24 and 48 h after LPS administration.
      Survival rate was recorded for 1 week. All surviving animals were assessed for
      cognitive function using the novel object recognition test, followed by
      measurement of hippocampal cytokine levels. In an additional set of experiments,
      the liver function test was performed. Furthermore, the effects of EGCG on
      cytokine release from microglia isolated from young and aged rats were assessed.
      RESULTS: The survival rate in LPS-treated control rats was 77.8%, which was
      decreased to 72.2 and 33.3% in the low and high EGCG groups, respectively. In the
      surviving animals, the LPS-treated control rats exhibited impaired cognitive
      performance and increased pro-inflammatory cytokine levels compared with
      untreated animals. None of these neurocognitive alterations were affected by low
      or high EGCG treatment. Blood chemical analysis showed co-administration of EGCG
      with LPS resulted in a marked increase in both aspartate aminotransferase and
      alanine aminotransferase levels. In addition, EGCG inhibited LPS-induced cytokine
      release, whereas the suppressive ability of EGCG was lower in aged microglia
      compared with in young microglia. CONCLUSIONS: Our findings demonstrated that
      EGCG cannot prevent hippocampal neuroinflammation and related memory deficits in
      aged rats surviving sepsis.

PMID- 28752433
TI  - A Phase I study to determine safety, pharmacokinetics, and pharmacodynamics of
      ANF-RHOTM, a novel PEGylated granulocyte colony-stimulating factor, in healthy
      volunteers.
AB  - Patients receiving pegfilgrastim (Neulasta(r)) for the treatment of neutropenia
      can experience bone pain following the injections required to achieve effective
      neutrophil levels. The safety, pharmacokinetic (PK), and pharmacodynamic (PD)
      profiles of ANF-RHOTM, a novel pegylated granulocyte colony stimulating factor,
      were assessed in a randomized, controlled, double-blind Phase 1 clinical study in
      healthy volunteers. Subjects received a single subcutaneous dose of ANF-RHO over
      a range of 6 doses (5-50 MUg/kg), placebo (saline), or the recommended clinical
      dose of pegfilgrastim administered at the labeled fixed 6 mg dosage (equivalent
      to 80-100 MUg/kg). The primary outcome measure was safety and tolerability.
      Secondary outcomes included PK and PD effects on absolute neutrophil count (ANC)
      and number of CD34+ progenitor cells. Severity of bone pain was also assessed. In
      healthy volunteers, ANF-RHO was administered at ascending doses up to 50 MUg/kg
      without significant adverse effects; appeared to be better (5 to 30 MUg/kg) or
      equally well (50 MUg/kg) tolerated, and had lower mean bone pain scores as
      compared to pegfilgrastim. ANF-RHO achieved CD34+ and ANC numbers at
      significantly lower doses, and had a significantly longer circulating half-life
      than pegfilgrastim. These results suggest that ANF-RHO can be provided less
      frequently, at a lower dose, and with fewer side effects. ANF-RHO had unique,
      prolonged PK/PD attributes as compared to marketed pegfilgrastim, suggesting that
      it may provide an improved clinical benefit in further clinical studies in
      patients with chemotherapy-induced or chronic idiopathic neutropenia.

PMID- 28752434
TI  - Recombinant Escherichia coli cultivation in a pressurized airlift bioreactor:
      assessment of the influence of temperature on oxygen transfer and uptake rates.
AB  - Temperature influences the rates of oxygen transfer (OTR) and uptake (q O2) in
      aerobic bioprocesses. Hence, joint analysis of q O2 and OTR at variable
      temperature is essential for bioprocess optimization and control. However, no
      such analyses have yet been reported for cultures of engineered E. coli producing
      recombinant proteins. E. coli cultivations at different temperatures (27-37 
      degrees C) were performed using a 5-L stirred tank bioreactor (STB), and a 5-L
      airlift bioreactor (ALB) was used to measure k L a and validate models of q O2
      and OTR. The equations were then employed to evaluate the cultivation process in
      the ALB at different pressures (0.1-0.4 MPa) and temperatures (27-37  degrees C).
      The results showed that the positive effect of temperature on k L a was more
      pronounced than the negative influence on oxygen solubility, increasing the OTR
      in the ALB. The specific growth rate and temperature influenced q O2. In contrast
      to previous reports, the results showed that q O2 was not explicitly affected by
      recombinant protein synthesis. In addition, model predictions revealed that
      biomass concentration and productivity were greatly improved by pressurization of
      the system and use of a lower temperature.

PMID- 28752435
TI  - [Importance of repeated liver resection in recurrent intrahepatic
      cholangiocarcinoma].

PMID- 28752436
TI  - [Organ-preserving surgery for rectal cancer].

PMID- 28752437
TI  - [Stent vs. stoma in malignant colon obstruction - long term results].

PMID- 28752438
TI  - [Blunt and penetrating thoracic trauma].
AB  - In most cases blunt chest trauma leads to fractures of the bony thorax, i. e.
      ribs. In the case of accompanying hemothorax or pneumothorax initial management
      consists of chest tube drainage by mini-thoracotomy. Subsequently patients with
      blunt chest trauma have to be transferred to the intensive care unit as these
      patients are at risk of pulmonary insufficiency or persistent blood loss via the
      chest tube. Injury to the great vessels or heart requires trauma care in
      specialized centers. Penetrating trauma is always surgically treated and the
      foreign body is removed in the operating room (OR). Life-threatening conditions,
      such as tension pneumothorax have to be treated by thorax drainage prior to
      hospital admission.

PMID- 28752439
TI  - Psychometrics in action, science as practice.
AB  - Practitioners in health sciences education and assessment regularly use a range
      of psychometric techniques to analyse data, evaluate models, and make crucial
      progression decisions regarding student learning. However, a recent editorial
      entitled "Is Psychometrics Science?" highlighted some core epistemological and
      practical problems in psychometrics, and brought its legitimacy into question.
      This paper attempts to address these issues by applying some key ideas from
      history and philosophy of science (HPS) discourse. I present some of the
      conceptual developments in HPS that have bearing on the psychometrics debate.
      Next, by shifting the focus onto what constitutes the practice of science, I
      discuss psychometrics in action. Some incorrectly conceptualize science as an
      assemblage of truths, rather than an assemblage of tools and goals.
      Psychometrics, however, seems to be an assemblage of methods and techniques.
      Psychometrics in action represents a range of practices using specific tools in
      specific contexts. This does not render the practice of psychometrics meaningless
      or futile. Engaging in debates about whether or not we should regard
      psychometrics as 'scientific' is, however, a fruitless enterprise. The key
      question and focus should be whether, on what grounds, and in what contexts, the
      existing methods and techniques used by psychometricians can be justified or
      criticized.

PMID- 28752441
TI  - Pathophysiology of Alpha-1 Antitrypsin Deficiency Liver Disease.
AB  - Classical alpha-1 antitrypsin (a1AT) deficiency is an autosomal recessive disease
      associated with an increased risk of liver disease in adults and children, and
      with lung disease in adults (Teckman and Jain, Curr Gastroenterol Rep 16(1):367,
      2014). The vast majority of the liver disease is associated with homozygosity for
      the Z mutant allele, the so-called PIZZ. These homozygous individuals synthesize
      large quantities of a1AT mutant Z protein in the liver, but the mutant protein
      folds improperly during biogenesis and approximately 85% of the molecules are
      retained within the hepatocytes rather than appropriately secreted. The resulting
      low, or "deficient," serum level leaves the lungs vulnerable to inflammatory
      injury from uninhibited neutrophil proteases. Most of the mutant Z protein
      molecules retained within hepatocytes are directed into intracellular proteolysis
      pathways, but some molecules remain in the endoplasmic reticulum for long periods
      of time. Some of these molecules adopt an unusual aggregated or "polymerized"
      conformation (Duvoix et al., Rev Mal Respir 31(10):992-1002, 2014). It is thought
      that these intracellular polymers trigger a cascade of intracellular injury which
      can lead to end-organ liver injury including chronic hepatitis, cirrhosis, and
      hepatocellular carcinoma (Lindblad et al., Hepatology 46(4):1228-1235, 2007). The
      hepatocytes with the largest accumulations of mutant Z polymers undergo apoptotic
      death and possibly other death mechanisms. This intracellular death cascade
      appears to involve ER stress, mitochondrial depolarization, and caspase cleavage,
      and is possibly linked to autophagy and redox injury. Cells with lesser burdens
      of mutant Z protein proliferate to maintain the liver cell mass. This chronic
      cycle of cell death and regeneration activates hepatic stellate cells and
      initiates the process of hepatic fibrosis. Cirrhosis and hepatocellular carcinoma
      then result in some patients. Since not all patients with the same homozygous
      PIZZ genotype develop end-stage disease, it is hypothesized that there is likely
      to be a strong influence of genetic and environmental modifiers of the injury
      cascade and of the fibrotic response.

PMID- 28752442
TI  - Pathophysiology of Alpha-1 Antitrypsin Lung Disease.
AB  - Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by
      low serum levels of alpha-1 antitrypsin (AAT). Loss of AAT disrupts the protease
      antiprotease balance in the lungs, allowing proteases, specifically neutrophil
      elastase, to act uninhibited and destroy lung matrix and alveolar structures.
      Destruction of these lung structures classically leads to an increased risk of
      developing emphysema and chronic obstructive pulmonary disease (COPD), especially
      in individuals with a smoking history. It is estimated that 3.4 million people
      worldwide have AATD. However, AATD is considered to be significantly
      underdiagnosed and underrecognized by clinicians. Contributing factors to the
      diagnostic delay of approximately 5.6 years are: inadequate awareness by
      healthcare providers, failure to implement recommendations from the American
      Thoracic Society/European Respiratory Society, and the belief that AATD testing
      is not warranted. Diagnosis can be attained using qualitative or quantitative
      laboratory testing. The only FDA approved treatment for AATD is augmentation
      therapy, although classically symptoms have been treated similarly to those of
      COPD. Future goals of AATD treatment are to use gene therapy using vector systems
      to produce therapeutic levels of AAT in the lungs without causing a systemic
      inflammatory response.

PMID- 28752440
TI  - Longitudinal validity and reliability of the Myeloma Patient Outcome Scale
      (MyPOS) was established using traditional, generalizability and Rasch
      psychometric methods.
AB  - PURPOSE: The Myeloma Patient Outcome Scale (MyPOS) was developed to measure
      quality of life in routine clinical care. The aim of this study was to determine
      its longitudinal validity, reliability, responsiveness to change and its
      acceptability. METHODS: This 14-centre study recruited patients with multiple
      myeloma. At baseline and then every two months for 5 assessments, patients
      completed the MyPOS. Psychometric properties evaluated were as follows: (a)
      confirmatory factor analysis and scaling assumptions (b) reliability:
      Generalizability theory and Rasch analysis, (c) responsiveness and minimally
      important difference (MID) relating changes in scores between baseline and
      subsequent assessments to an external criterion, (d) determining the
      acceptability of self-monitoring. RESULTS: 238 patients with multiple myeloma
      were recruited. Confirmatory factor analysis found three subscales; criteria for
      scaling assumptions were satisfied except for gastrointestinal items and the
      Healthcare support scale. Rasch analysis identified limitations of suboptimal
      scale-to-sample targeting, resulting in floor effects. Test-retest reliability
      indices were good (R = > 0.97). Responsiveness analysis yielded an MID of +2.5
      for improvement and -4.5 for deterioration. CONCLUSIONS: The MyPOS demonstrated
      good longitudinal measurement properties, with potential areas for revision being
      the Healthcare Support subscale and the rating scale. The new psychometric
      approaches should be used for testing validity of monitoring in clinical
      settings.

PMID- 28752443
TI  - Measuring and Interpreting Serum AAT Concentration.
AB  - Deficiency of alpha-1 antitrypsin (AAT) is caused by mutations in the SERPINA1
      gene that results in low concentrations of AAT in circulation. The low AAT
      concentration can result in uninhibited neutrophil elastase activity in the lung,
      leading to pulmonary tissue damage and lung disease. Clinical evaluation for
      possible AAT deficiency includes two critical components: measuring AAT
      concentration in serum and identification of AAT deficiency alleles. In this
      chapter the methods by which AAT concentration can be measured in the clinical
      laboratory are described. The two most common methodologies for AAT
      quantification employ immunometric techniques, specifically nephelometry and
      turbidimetry, which are both based on light scatter technology. The AAT in the
      patient sample is combined with an anti-AAT polyclonal antibody solution leading
      to polymer formation and a proportional amount of subsequent light scatter.
      Descriptions of each method are presented, and specifics of quality control and
      assay parameters are discussed. A special discussion focuses on interpretation of
      results in the context of the different AAT genetic phenotypes and in the context
      of patients with active inflammatory conditions. Emerging techniques for AAT
      quantitation by mass spectrometry are also described given that both AAT
      quantitation and allele identification can be performed on the same assay.

PMID- 28752444
TI  - AAT Phenotype Identification by Isoelectric Focusing.
AB  - Isoelectric focusing (IEF) electrophoresis is considered to be the gold standard
      test for determining an individual's AAT phenotype. IEF electrophoresis is a
      technique used to separate proteins by differences in their isoelectric point
      (pI). Testing is performed on serum that is applied to an agarose gel containing
      ampholytes which create a pH gradient ranging from 4.2 to 4.9. Variants of AAT
      are therefore separated from each other and, after visualization of the focused
      protein bands using immunochemical techniques, can be identified and an AAT
      phenotype determined.In this chapter we elaborate on IEF electrophoresis as it
      relates to AAT phenotyping, describe practical approaches to AAT variant
      identification, and discuss circumstances in which phenotype testing may be
      inaccurate.

PMID- 28752445
TI  - Laboratory Diagnosis by Genotyping.
AB  - Alpha-1 antitrypsin (AAT) genotyping is useful to confirm the clinical diagnosis
      of AAT deficiency and determine the specific allelic variant. Genotyping is the
      reference standard procedure for identifying rare allelic variants and
      characterizing new variants. It is also useful when there is a discrepancy
      between the patients' AAT levels and their phenotypes. AAT genotype is determined
      by an allele-specific genotyping assay for the S, Z, and Mmalton variants and by
      exome sequencing.

PMID- 28752446
TI  - Genotyping Protocol for the Alpha-1 Antitrypsin (PiZ) Mouse Model.
AB  - The most common alpha-1 antitrypsin (AAT) mutant variant is a missense mutation
      (E342K), commonly referred to as PiZ. A transgenic mouse model exists that
      expresses the mutant human PiZ AAT gene. This protocol outlines the procedure
      used to extract DNA from and genotype AAT transgenic (PiZ) mice.

PMID- 28752447
TI  - Elastase-Induced Lung Emphysema Models in Mice.
AB  - Pulmonary emphysema is one of the distinct pathological forms of chronic
      obstructive pulmonary disease (COPD) that is accompanied by gradual elimination
      of alveolar tissue, causing reductions in lung recoil and leading to difficulty
      in breathing. As there is no cure for emphysema, animal models are often used to
      better understand the pathogenesis and progression of the disease. One widely
      used animal model of emphysema is the elastase treatment. In this chapter, we
      describe two methods of elastase-induced emphysema in mice. The first is a single
      dose treatment, whereby elastase is introduced oropharengeally into the lung and
      the structure and/or function of the lungs are studied between 2 days and 4 weeks
      following the treatment. The second method consists of exposing mice repeatedly
      (four times) to elastase intratracheally and observing the effects of the
      treatment 1-4 weeks following the last administration of the enzyme. Both
      protocols are described in detail, and examples of lung structure and function of
      the emphysematous mouse lung are provided.

PMID- 28752448
TI  - Assessing Structure-Function Relations in Mice Using the Forced Oscillation
      Technique and Quantitative Histology.
AB  - The structure and function of the lung gradually becomes compromised during the
      progression of emphysema. In this chapter, we first describe how to assess and
      evaluate lung function using the forced oscillation technique. Next, we provide
      details on how to use the Flexivent system to measure respiratory mechanical
      parameters in mice. We also describe the outlines of how to set up a homemade
      forced oscillatory system and use it to measure respiratory mechanics. To
      characterize the structure from standard histological images, we describe a
      method that is highly sensitive to early emphysema. Correlating structural
      information such as equivalent alveolar diameter and its variance with
      respiratory elastance or compliance, provides structure-function relationships
      that can subsequently reveal novel mechanisms of emphysema progression or be used
      to track the effectiveness of treatment.

PMID- 28752449
TI  - Practical Methods for Assessing Emphysema Severity Based on Estimation of Linear
      Mean Intercept (Lm) in the Context of Animal Models of Alpha-1 Antitrypsin
      Deficiency.
AB  - Alpha-1 antitrypsin deficiency is typified by panacinar emphysema in humans.
      Whilst animal models of (alpha1A-TD) that more accurately reflect the histology
      and molecular pathology of alpha1A-TD are in development, it is timely to discuss
      methods to assess emphysema severity. Several methods exist to quantify emphysema
      from histologic sections, including linear mean intercept (Lm), equivalent
      diameters (D) or their statistical derivatives (D2), and more recently
      probability models of D2 ("severity index"). Given proper attention to lung
      inflation, reference volume, and random sampling, Lm determined by intersect
      point counting provides a robust analytical tool to quantify emphysema severity.
      Details of lung preparation, processing for random sampling, and batch processing
      of prescreened images are provided herein.

PMID- 28752450
TI  - Design, Cloning, and In Vitro Screening of Artificial miRNAs to Silence Alpha-1
      Antitrypsin.
AB  - This protocol describes the design, cloning, and in vitro screening of artificial
      microRNAs (miRNAs) to silence alpha-1 antitrypsin (AAT). This method would be of
      interest to silence AAT in a variety of in vitro or in vivo models, and
      prevalidated sequences against human AAT are provided. This simple 5-day protocol
      may more generally be used to design artificial miRNAs against any transcript.

PMID- 28752451
TI  - Methods to Identify and Characterize siRNAs Targeting Serpin A1 In Vitro and In
      Vivo Using RNA Interference.
AB  - RNAi is a powerful tool that can be used to probe gene function as well as for
      therapeutic intervention. We describe a workflow and methods to identify screen
      and select potent and specific siRNAs in vitro and in vivo using qPCR-based
      methods as well as an AAT activity assay. We apply these techniques to a set of
      siRNAs targeting rat AAT, and use this set to exemplify the cell-based and in
      vivo data that can be generated using these methods.

PMID- 28752452
TI  - Knockdown of Z Mutant Alpha-1 Antitrypsin In Vivo Using Modified DNA Antisense
      Oligonucleotides.
AB  - Alpha-1 antitrypsin (AAT) is a serum protease inhibitor, mainly expressed in and
      secreted from hepatocytes, important for regulating neutrophil elastase activity
      among other proteases. Various mutations in AAT cause alpha-1 antitrypsin
      deficiency (AATD), a rare hereditary disorder that results in liver disease due
      to accumulation of AAT aggregates and lung disease from excessive neutrophil
      elastase activity. PiZ transgenic mice contain the human AAT genomic region
      harboring the most common AATD mutation, the Glu342Lys (Z) point mutation. These
      mice effectively recapitulate the liver disease exhibited in AATD patients,
      including AAT protein aggregates, hepatocyte death, and eventual liver fibrosis.
      Previously, we demonstrated that modified antisense oligonucleotides (ASOs) can
      dramatically reduce Z-AAT RNA and protein levels in PiZ mice enabling inhibition,
      prevention, and reversal of the associated liver disease. Here, we describe in
      detail usage of AAT-ASOs to knock down Z-AAT in PiZ mice with a focus on
      preparation and in vivo delivery of ASOs, as well as detailed workflows
      pertaining to the analysis of Z-AAT mRNA, plasma protein, and soluble/insoluble
      liver protein levels following ASO administration.

PMID- 28752453
TI  - Immunohistochemistry Staining for Human Alpha-1 Antitrypsin.
AB  - Immunohistochemistry (IHC) is a powerful immunology-based method that is used to
      study the location of proteins in cells and tissues. There have been numerous
      advancements in IHC technology that continually increase the sensitivity and
      specificity through which this method can be used to generate new discoveries.
      Similarly, Alpha-1 Antitrypsin (AAT) IHC can be used to study AAT protein
      expression within the human liver or exogenous AAT that is delivered through gene
      therapy. Here, we describe a highly sensitive method to detect the AAT antigen in
      formalin-fixed paraffin-embedded human or mouse tissues.

PMID- 28752454
TI  - Periodic Acid-Schiff Staining with Diastase.
AB  - Periodic Acid-Schiff (PAS) with diastase (PAS-D) refers to the use of the PAS
      stain in combination with diastase, which is an enzyme that digests the glycogen.
      The purpose of using the PAS-D procedure is to differentiate glycogen from other
      PAS-positive elements in tissue samples. The PAS-D method is also used for
      periportal liver staining of AAT polymer inclusions that are seen in alpha-1
      antitrypsin deficiency disease. Here, we describe the procedure of PAS-D staining
      in formalin-fixed, paraffin-embedded human liver tissues.

PMID- 28752455
TI  - Protocol for Directed Differentiation of Human Induced Pluripotent Stem Cells
      (iPSCs) to a Hepatic Lineage.
AB  - Directed differentiation is a powerful cell culture technique where developmental
      pathways are applied to a pluripotent progenitor in order to generate specific
      terminally differentiated cell populations. Here, we describe a serum-free
      protocol using growth factors in defined concentrations to derive iPSC-hepatic
      cells starting from both feeder and feeder-free conditions. The generated iPSC
      hepatic cells are developmentally similar to fetal stage hepatocytes, and when
      generated from patients with genetic mutations such as alpha-1 antitrypsin
      deficiency recapitulate pathologic changes associated with clinical disease, such
      as protein misfolding, intracellular retention of misfolded proteins, and
      elevated levels of ER stress.

PMID- 28752456
TI  - Isolation of Kupffer Cells and Hepatocytes from a Single Mouse Liver.
AB  - Liver perfusion is a common technique used to isolate parenchymal and non
      parenchymal liver cells for in vitro experiments. This method allows hepatic
      cells to be separated based on their size and weight, by centrifugation using a
      density gradient. To date, other methods allow the isolation of only one viable
      hepatic cellular fraction from a single mouse; either parenchymal (hepatocytes)
      or non-parenchymal cells (i.e., Kupffer cells or hepatic stellate cells). Here,
      we describe a method to isolate both hepatocytes and Kupffer cells from a single
      mouse liver, thereby providing the unique advantage of studying different liver
      cell types that have been isolated from the same organism.

PMID- 28752457
TI  - Alpha-1 Antitrypsin Transcytosis and Secretion.
AB  - Protective levels of Alpha-1 antitrypsin (A1AT) are achieved in the lung through
      the uptake of the pulmonary vasculature of hepatocyte-secreted A1AT. The anti
      inflammatory, anti-apoptotic, and anti-protease properties of A1AT are critical
      toward maintaining the function of pulmonary endothelial and epithelial cells and
      for the structural integrity of the pulmonary interstitium. To perform these
      functions A1AT must cross the pulmonary-endothelial barrier. Using transwell
      inserts, we have demonstrated that the endocytosis of A1AT at the apical surface
      of endothelial cells, followed by the transcytosis and secretion at the
      basolateral surface, is a mechanism through which A1AT is transported into the
      lung epithelium and interstitium.

PMID- 28752458
TI  - Measuring the Effect of Histone Deacetylase Inhibitors (HDACi) on the Secretion
      and Activity of Alpha-1 Antitrypsin.
AB  - Alpha-1 antitrypsin deficiency (AATD) is a protein conformational disease with
      the most common cause being the Z-variant mutation in alpha-1 antitrypsin (Z
      AAT). The misfolded conformation triggered by the Z-variant disrupts cellular
      proteostasis (protein folding) systems and fails to meet the endoplasmic
      reticulum (ER) export metrics, leading to decreased circulating AAT and deficient
      antiprotease activity in the plasma and lung. Here, we describe the methods for
      measuring the secretion and neutrophil elastase (NE) inhibition activity of AAT/Z
      AAT, as well as the response to histone deacetylase inhibitor (HDACi), a major
      proteostasis modifier that impacts the secretion and function of AATD from the
      liver to plasma. These methods provide a platform for further therapeutic
      development of proteostasis regulators for AATD.

PMID- 28752459
TI  - Expression and Purification of Active Recombinant Human Alpha-1 Antitrypsin (AAT)
      from Escherichia coli.
AB  - Well-established genetic manipulation procedures along with a fast doubling time,
      the ability to grow in inexpensive media, and easy scaleup make Escherichia coli
      (E. coli) a preferred recombinant protein expression platform. Human alpha-1
      antitrypsin (AAT) and other serpins are easily expressed in E. coli despite their
      metastability and complicated topology. Serpins can be produced as soluble
      proteins or aggregates in inclusion bodies, and both forms can be purified to
      homogeneity. In this chapter, we describe an ion-exchange chromatography-based
      protocol that we have developed involving the use of two anion-exchange columns
      to purify untagged human AAT from E. coli. We also outline methods that can be
      used to determine the inhibitory activity of both AAT in cell lysates and
      purified AAT. Our protocol for the purification of bacterially expressed AAT
      yields pure and active protein at 6-7 mg/l culture.

PMID- 28752460
TI  - Quantification of Total Human Alpha-1 Antitrypsin by Sandwich ELISA.
AB  - In this chapter we describe an enzyme-linked immunosorbent assay (ELISA) to
      quantitatively measure human alpha-1 antitrypsin (AAT) protein levels in serum,
      other body fluids or liquid media. This assay can be used to measure the
      expression of the human AAT (hAAT) gene in a variety of gene transfer or gene
      downregulation experiments.A hAAT-specific capture antibody and a HRP-conjugated
      anti-AAT detection antibody are used in this assay. The conjugated anti-AAT used
      in this protocol, instead of the typical sandwich which employs an unconjugated
      antibody followed by a specifically conjugated IgG, makes the assay simpler and
      decreases variability. This provides a useful tool to evaluate the AAT levels in
      clinical and research samples and can allow fairly rapid testing of a large
      number of samples.

PMID- 28752461
TI  - Quantification of Murine AAT by Direct ELISA.
AB  - This methods chapter elaborates on how a direct enzyme-linked immunosorbent assay
      (ELISA) is used to specifically detect and quantify murine alpha-1 antitrypsin
      (AAT). As a direct ELISA, it lacks some sensitivity as compared to the "sandwich"
      ELISA method; however, it does reliably differentiate between samples with
      varying amounts of the mouse AAT protein. This protocol relies on the principle
      of adsorption to coat each well with sera proteins, whereas detection occurs
      specifically using a two-step antibody combination. This procedure effectively
      identifies and quantifies murine AAT from a wide variety of samples including
      mouse serum, cell culture medium, and cell or tissue lysate.

PMID- 28752462
TI  - Quantification of Z-AAT by a Z-Specific "Sandwich" ELISA.
AB  - This protocol describes an enzyme-linked immunosorbent assay (ELISA) to
      specifically detect Z-alpha-1 antitrypsin (AAT), the most common protein variant
      associated with alpha-1 antitrypsin deficiency. This "sandwich" ELISA relies on
      an anti-Z-AAT specific capture antibody and a HRP-conjugated anti-AAT detection
      antibody. This method would be of interest to identify and quantify Z-AAT in a
      variety of samples such as cell culture medium, cell or tissue lysate, animal or
      patient serum. Because this method is specific and sensitive, it would be
      particularly valuable for detection of Z-AAT in the presence of background M-AAT,
      for instance when quantifying silencing of Z-AAT in patients undergoing M-AAT
      augmentation therapy.

PMID- 28752463
TI  - Semiquantitation of Monomer and Polymer Alpha-1 Antitrypsin by Centrifugal
      Separation and Assay by Western Blot of Soluble and Insoluble Components.
AB  - Alpha-1 antitrypsin (a1AT) deficiency, in its classical form, is an autosomal
      recessive disease associated with an increased risk of liver disease in adults
      and children, and with lung disease in adults. The vast majority of liver disease
      is associated with homozygosity for the Z mutant allele, also called PiZZ. This
      homozygous allele synthesizes large quantities of a1AT mutant Z protein in the
      liver, but the mutant protein also folds improperly during biogenesis. As a
      result, approximately 85% of the molecules are retained within the hepatocytes
      instead of being appropriately secreted. The resulting low, or "deficient," serum
      level leaves the lungs vulnerable to inflammatory injury from uninhibited
      neutrophil proteases. Most of the mutant Z protein retained within hepatocytes is
      directed into intracellular proteolysis pathways, but some molecules remain in
      the endoplasmic reticulum for long periods of time and others adopt an unusual
      aggregated or "polymerized" conformation. It is thought that these intracellular
      polymers trigger a cascade of intracellular injury which can lead to end organ
      liver injury including chronic hepatitis, cirrhosis, and hepatocellular
      carcinoma. It is widely accepted that the disease causing factor in mutant Z
      alpha-1 antitrypsin deficiency (AATD-Z) is the toxic build-up of the mutant Z
      protein. Since misfolding of some but not all of the Z protein during its
      maturation leads to homopolymerization, an assay to assess the amount of normally
      folded ATZ and accumulated polymeric ATZ would be very useful. Here we describe a
      method to semiquantitatively assess these two fractions in a tissue or cell
      culture source.

PMID- 28752464
TI  - Electrophoresis- and FRET-Based Measures of Serpin Polymerization.
AB  - Many serpinopathies, including alpha-1 antitrypsin (A1AT) deficiency, are
      associated with the formation of unbranched polymer chains of mutant serpins. In
      vivo, this deficiency is the result of mutations that cause kinetic or
      thermodynamic destabilization of the molecule. However, polymerization can also
      be induced in vitro from mutant or wild-type serpins under destabilizing
      conditions. The characteristics of the resulting polymers are dependent upon
      induction conditions. Due to their relationship to disease, serpin polymers,
      mainly those formed from A1AT, have been widely studied. Here, we describe
      Forster resonance energy transfer (FRET) and gel-based approaches for their
      characterization.

PMID- 28752465
TI  - Therapeutics: Alpha-1 Antitrypsin Augmentation Therapy.
AB  - Subjects with alpha-1 antitrypsin deficiency who develop pulmonary disease are
      managed following general treatment guidelines, including disease management
      interventions. In addition, administration of intravenous infusions of alpha-1
      proteinase inhibitor (augmentation therapy) at regular schedules is a specific
      therapy for individuals with AATD with pulmonary involvement.This chapter
      summarizes the manufacturing differences of commercially available formulations
      and the available evidence of the effects of augmentation therapy. Biologically,
      there is clear evidence of in vivo local antiprotease effects in the lung and
      systemic immunomodulatory effects. Clinically, there is cumulative evidence of
      slowing lung function decline and emphysema progression. The optimal dose of
      augmentation therapy is being revised as well as more individualized assessment
      of who needs this therapy.

PMID- 28752466
TI  - Therapeutic Options in Alpha-1 Antitrypsin Deficiency: Liver Transplantation.
AB  - Alpha-1 antitrypsin deficiency is the commonest genetic condition leading to
      liver transplantation in childhood. It remains unclear why only a minority of
      individuals carrying homozygous PiZ phenotype has liver disease, but also why of
      those only about a quarter develops end stage liver disease, requiring liver
      transplantation. This intervention has now become routine worldwide with 1-year
      patient survival rates well above 90%. As for all autosomal recessive conditions
      liver donation from anonymous cadaveric sources is preferred to living related
      parental donors, due to their presumed heterozygous state.

PMID- 28752467
TI  - Therapeutics: Gene Therapy for Alpha-1 Antitrypsin Deficiency.
AB  - This review seeks to give an overview of alpha-1 antitrypsin deficiency,
      including the different disease phenotypes that it encompasses. We then describe
      the different therapeutic endeavors that have been undertaken to address these
      different phenotypes. Lastly we discuss future potential therapeutics, such as
      genome editing, and how they may play a role in treating alpha-1 antitrypsin
      deficiency.

PMID- 28752468
TI  - Erratum to: Implications of Impaired Endurance Performance Following Single Bouts
      of Resistance Training: An Alternate Concurrent Training Perspective.

PMID- 28752469
TI  - 8th Edition of the AJCC Cancer Staging Manual: Pancreas and Hepatobiliary
      Cancers.

PMID- 28752471
TI  - Calcium Phosphate Particles as Pulmonary Delivery System for Interferon-alpha in
      Mice.
AB  - Systemically administered interferons are rapidly cleared from the circulation
      thus requiring frequent dosing to maintain the therapeutic levels of circulating
      interferon. This is particularly problematic for their use in the treatment of
      chronic diseases. The purpose of this study was to evaluate the potential of
      proprietary calcium phosphate (CaP) particles to deliver biologically active
      interferon alpha (IFNalpha) via the lungs into systemic circulation. Recombinant
      human IFNalpha-2a was formulated with proprietary CaP particles. In vitro
      biological activity of IFNalpha was assessed for its potential to activate IFN
      induced cellular pathways in HEK-Blu-IFN alpha/beta cell cultures. Antiviral
      activity was evaluated against vesicular stomatitis virus (VSV) infection of HeLa
      cells. Male BALB/c mice were used to evaluate the absorption of IFNalpha from CaP
      IFNalpha across the lungs following intratracheal (IT) instillation. Serum
      IFNalpha concentrations up to 9 h post-treatment were determined. Data were
      analyzed to obtain pharmacokinetic (PK) parameters. Data from these studies
      indicated that IFNalpha formulated with CaP retains its biological activity, and
      it is transported into circulation in a dose-dependent manner. PK analysis showed
      larger than two-fold area under the serum concentration-time curve (AUC) for CaP
      IFNalpha compared to non-formulated IFNalpha administered IT. The IFNalpha
      formulated with CaP had two-fold longer half-life (t1/2) and mean residence time
      (MRT) relative to IFNalpha alone administered by injection. Clearance of CaP
      IFNalpha was slower than IFNalpha administered IM or IT. Relative bioavailability
      of CaP-IFNalpha was 1.3-fold of IFNalpha injection and twofold of IFNalpha
      administered IT. Furthermore, inhalation of aerosolized CaP did not indicate any
      lung toxicity in animals.

PMID- 28752470
TI  - Comparative Study of Novel Fluorescent Cyanine Nucleotides: Hybridization
      Analysis of Labeled PCR Products Using a Biochip.
AB  - This study investigated the synthesis and substrate properties of Cy5-labeled
      dUTP derivatives with different substituents, linkers between the dye unit and
      pyrimidine heterocycle and fluorophore charges. Fluorescently labeled nucleoside
      triphosphates were studied as substrates using multiplex PCR with Taq and Vent
      (exo-) DNA polymerases, the typical representatives of the A and B polymerase
      families. The efficiency of nucleotide incorporation during PCR was assessed with
      a multi-parameter hybridization analysis using a diagnostic DNA microarray. The
      hybridization analysis indirectly estimates the incorporation efficiency of dye
      labeled nucleotides in multiplex PCR. Our results demonstrated higher
      efficiencies of substrates with electrically neutral dyes than electropositive
      and electronegative Cy5 residues.

PMID- 28752472
TI  - Technical challenges related to implementation of a formula one real time data
      acquisition and analysis system in a paediatric intensive care unit.
AB  - Most existing, expert monitoring systems do not provide the real time continuous
      analysis of the monitored physiological data that is necessary to detect
      transient or combined vital sign indicators nor do they provide long term storage
      of the data for retrospective analyses. In this paper we examine the feasibility
      of implementing a long term data storage system which has the ability to
      incorporate real-time data analytics, the system design, report the main
      technical issues encountered, the solutions implemented and the statistics of the
      data recorded. McLaren Electronic Systems expertise used to continually monitor
      and analyse the data from F1 racing cars in real time was utilised to implement a
      similar real-time data recording platform system adapted with real time analytics
      to suit the requirements of the intensive care environment. We encountered many
      technical (hardware and software) implementation challenges. However there were
      many advantages of the system once it was operational. They include: (1) The
      ability to store the data for long periods of time enabling access to historical
      physiological data. (2) The ability to alter the time axis to contract or expand
      periods of interest. (3) The ability to store and review ECG morphology
      retrospectively. (4) Detailed post event (cardiac/respiratory arrest or other
      clinically significant deteriorations in patients) data can be reviewed
      clinically as opposed to trend data providing valuable clinical insight. Informed
      mortality and morbidity reviews can be conducted. (5) Storage of waveform data
      capture to use for algorithm development for adaptive early warning systems.
      Recording data from bed-side monitors in intensive care/wards is feasible. It is
      possible to set up real time data recording and long term storage systems. These
      systems in future can be improved with additional patient specific metrics which
      predict the status of a patient thus paving the way for real time predictive
      monitoring.

PMID- 28752473
TI  - Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with
      Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post
      Marketing Experience.
AB  - INTRODUCTION: Eslicarbazepine acetate was first approved in the European Union in
      2009 as adjunctive therapy in adults with partial-onset seizures with or without
      secondary generalization. OBJECTIVE: The objective of this study was to review
      the safety profile of eslicarbazepine acetate analyzing the data from several
      clinical studies to 6 years of post-marketing surveillance. METHODS: We used a
      post-hoc pooled safety analysis of four phase III, double-blind, randomized,
      placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine
      acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in
      special populations of patients aged >=65 years with partial-onset seizures (BIA
      2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal
      impairment (BIA-2093-112) are also considered. The incidences of treatment
      emergent adverse events, treatment-emergent adverse events leading to
      discontinuation, and serious adverse events were analyzed. The global safety
      database of eslicarbazepine acetate was analyzed for all cases from post
      marketing surveillance from 1 October, 2009 to 21 October, 2015. RESULTS: From a
      pooled analysis of four phase III studies, it was concluded that the incidence of
      treatment-emergent adverse events, treatment-emergent adverse events leading to
      discontinuation, and adverse drug reactions were dose dependent. Dizziness,
      somnolence, headache, and nausea were the most common treatment-emergent adverse
      events (>=10% of patients) and the majority were of mild-to-moderate intensity.
      No dose-dependent trend was observed for serious adverse events and individual
      serious adverse events were reported in less than 1% of patients. Hyponatremia
      was classified as a possibly related treatment-emergent adverse event in phase
      III studies (1.2%); however, after 6 years of post-marketing surveillance it
      represents the most frequently (10.2%) reported adverse drug reaction, with more
      than half of these cases occurring with eslicarbazepine acetate at daily doses of
      1200 mg. Other adverse drug reactions reported in post-marketing surveillance are
      seizure (5.8%), dizziness (4.1%), rash (2.6%), and fatigue (2.1%). The safety
      profile of eslicarbazepine acetate in renal and hepatic impairment subjects
      (phase I studies) and in elderly patients (phase III study) did not raise any
      specific concern. CONCLUSION: After 6 years of post-marketing surveillance,
      eslicarbazepine acetate maintains a similar safety profile to that observed in
      pivotal clinical studies.

PMID- 28752474
TI  - Secondary Sclerosing Cholangitis: a Review of Recent Literature.
AB  - PURPOSE OF REVIEW: Secondary sclerosing cholangitis is an emerging entity. Yet,
      because of the low incidence and varying etiologies of this disease, the
      literature is not robust. There are mainly case reports and small studies
      evaluating the disease. Our aim in this review is to bring the reader up to date
      with recent literature on secondary sclerosing cholangitis including the disease
      presentation, course, prognosis, and treatment options. RECENT FINDINGS: Numerous
      case reports have been published the last 5 years on secondary sclerosing
      cholangitis. We have divided them into infectious, drug-induced, ischemic,
      obstructive, and autoimmune etiologies. The bulk of the literature describes
      secondary sclerosing cholangitis in the critically ill patient. Secondary
      sclerosing cholangitis due to drugs or autoimmune causes seem to have the best
      prognosis. However, causes such as critical illness seem to have worse outcomes.

PMID- 28752475
TI  - Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current
      Views and Prospects.
AB  - PURPOSE OF REVIEW: The purpose of this study is to analyze the current evidence
      regarding the use of statins in patients with chronic liver disease and
      cirrhosis. RECENT FINDINGS: Chronic liver disease (CLD), cirrhosis, and its
      complications, including hepatocellular carcinoma (HCC), are significant public
      health problems. The use of statins in patients with CLD has been a matter of
      concern, and physicians are often reluctant to its prescription in these
      patients. This mainly relates to the potential occurrence of drug-induced liver
      injury. However, newer evidence from pre-clinical and clinical research has shown
      that statins are drugs with a potentially beneficial impact on the natural
      history of cirrhosis, on portal hypertension, and in HCC prevention. In this
      review, we summarize current evidence regarding the influence of statins in
      endothelial dysfunction in CLD, their ability to modulate hepatic fibrogenesis,
      and their vasoprotective effects in portal hypertension; we also focus on
      existing data about the impact of statins in cirrhosis development, progression,
      and complications and critically assess the current concerns about its use in
      patients with CLD.

PMID- 28752476
TI  - Bleeding Risk with Invasive Procedures in Patients with Cirrhosis and
      Coagulopathy.
AB  - PURPOSE OF REVIEW: Previous perceptions of cirrhosis as a hypocoagulable state
      have resulted in empirical blood product transfusions prior to invasive
      procedures. We evaluate procedure-related bleeding risks in patients with
      cirrhosis, assess the utility of conventional and newer global coagulation tests,
      and explore evidence surrounding prophylactic transfusion strategies. RECENT
      FINDINGS: Recent literature supports the concept of a rebalanced, albeit fragile,
      haemostasis equilibrium in cirrhosis, with a potential hypercoagulable tendency
      in stable patients. Standard coagulation tests provide a poor reflection of
      bleeding risks and yet are relied upon for transfusion thresholds. Consequently,
      a sizeable proportion of patients receive unnecessary blood products. The role of
      viscoelastic tests to guide transfusions requires further evaluation. In stable
      cirrhotic patients, procedure-related bleeding rates appear low. Prophylactic
      transfusion strategies based on arbitrary thresholds lack evidence of clinical
      benefit. There is a pressing need for point-of-care coagulation tests that
      represent the complex coagulopathy of cirrhosis and well-powered randomised
      controlled trials to develop evidence-based pre-procedure transfusion guidelines.

PMID- 28752477
TI  - Addition of biomarker panel improves prediction performance of American College
      of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator
      for cardiac risk assessment of elderly patients preparing for major non-cardiac
      surgery: a pilot study.
AB  - BACKGROUND: Number of elderly patients subjected to extensive surgical procedures
      in the presence of cardiovascular morbidities is increasing every year.
      Therefore, there is a need to make preoperative diagnostics more accurate. AIMS:
      To evaluate the usefulness of American College of Surgeons National Surgical
      Quality Improvement Program (ACS NSQIP) calculator as a predictive tool in
      preoperative assessment of cardiovascular risk in elderly patients. METHODS: This
      prospective pilot study included 78 patients who were being prepared for
      extensive non-cardiac surgeries under general anaesthesia. Their data have been
      processed on the interactive ACS NSQIP calculator. Blood sampling has been
      performed 7 days prior to surgery, and serum has been separated. Clinical, novel,
      and experimental biomarkers [hsCRP, H-FABP, and Survivin (BIRC5)] have been
      measured in specialized laboratories. RESULTS: Mean age of included patients was
      71.35 +/- 6.89 years. In the case of heart complications and mortality
      prediction, hsCRP and ACS NSQIP showed the highest specificity and sensitivity
      with AUC, respectively, 0.869 and 0.813 for heart complications and 0.883 and
      0.813 for mortality. When combined with individual biomarkers AUC of ACS NSQIP
      raised, but if we combined all three biomarkers with ACS NSQIP, AUC reached as
      much as 0.920 for heart complications and 0.939 for mortality. DISCUSSION: ACS
      NSQIP proved to reduce inaccuracy in preoperative assessment, but it cannot be
      used independently, which has already been proved by other authors. CONCLUSIONS:
      Our results indicate that ACS NSQIP represents an accurate tool for preoperative
      assessment of elderly patients, especially if combined with cardiac biomarkers.

PMID- 28752478
TI  - Coming to Grips with Ambiguity: Ion Mobility-Mass Spectrometry for Protein
      Quaternary Structure Assignment.
AB  - Multiprotein complexes are central to our understanding of cellular biology, as
      they play critical roles in nearly every biological process. Despite many
      impressive advances associated with structural characterization techniques, large
      and highly-dynamic protein complexes are too often refractory to analysis by
      conventional, high-resolution approaches. To fill this gap, ion mobility-mass
      spectrometry (IM-MS) methods have emerged as a promising approach for
      characterizing the structures of challenging assemblies due in large part to the
      ability of these methods to characterize the composition, connectivity, and
      topology of large, labile complexes. In this Critical Insight, we present a
      series of bioinformatics studies aimed at assessing the information content of IM
      MS datasets for building models of multiprotein structure. Our computational data
      highlights the limits of current coarse-graining approaches, and compelled us to
      develop an improved workflow for multiprotein topology modeling, which we
      benchmark against a subset of the multiprotein complexes within the PDB. This
      improved workflow has allowed us to ascertain both the minimal experimental
      restraint sets required for generation of high-confidence multiprotein
      topologies, and quantify the ambiguity in models where insufficient IM-MS
      information is available. We conclude by projecting the future of IM-MS in the
      context of protein quaternary structure assignment, where we predict that a more
      complete knowledge of the ultimate information content and ambiguity within such
      models will undoubtedly lead to applications for a broader array of challenging
      biomolecular assemblies. Graphical Abstract ?.

PMID- 28752479
TI  - Quantitative Proteomic Analysis of Optimal Cutting Temperature (OCT) Embedded
      Core-Needle Biopsy of Lung Cancer.
AB  - With recent advances in understanding the genomic underpinnings and oncogenic
      drivers of pathogenesis in different subtypes, it is increasingly clear that
      proper pretreatment diagnostics are essential for the choice of appropriate
      treatment options for non-small cell lung cancer (NSCLC). Tumor tissue
      preservation in optimal cutting temperature (OCT) compound is commonly used in
      the surgical suite. However, proteins recovered from OCT-embedded specimens pose
      a challenge for LC-MS/MS experiments, due to the large amounts of polymers
      present in OCT. Here we present a simple workflow for whole proteome analysis of
      OCT-embedded NSCLC tissue samples, which involves a simple trichloroacetic acid
      precipitation step. Comparisons of protein recovery between frozen versus OCT
      embedded tissue showed excellent consistency with more than 9200 proteins
      identified. Using an isobaric labeling strategy, we quantified more than 5400
      proteins in tumor versus normal OCT-embedded core needle biopsy samples. Gene
      ontology analysis indicated that a number of proliferative as well as squamous
      cell carcinoma (SqCC) marker proteins were overexpressed in the tumor, consistent
      with the patient's pathology based diagnosis of "poorly differentiated SqCC".
      Among the most downregulated proteins in the tumor sample, we noted a number of
      proteins with potential immunomodulatory functions. Finally, interrogation of the
      aberrantly expressed proteins using a candidate approach and cross-referencing
      with publicly available databases led to the identification of potential
      druggable targets in DNA replication and DNA damage repair pathways. We conclude
      that our approach allows LC-MS/MS proteomic analyses on OCT-embedded lung cancer
      specimens, opening the way to bring powerful proteomics into the clinic.
      Graphical Abstract ?.

PMID- 28752480
TI  - Evaluation of three adjuvants with respect to both adverse effects and the
      efficacy of antibody production to the Bm86 protein.
AB  - Cattle tick infestations remain an important burden for farmers in tropical area
      like in New Caledonia. With the development of acaricide resistance, tick
      vaccines should be an attractive alternative to control ticks but their efficacy
      needs to be improved. In this study three adjuvants were studied in an
      experimental tick vaccine with a Bm86 protein to assess their performance in
      terms of antibody productions and adverse reactions following vaccinations. The
      water-in-oil adjuvant ISA 61 VG led to higher antibody titers compared to a water
      in-oil-in-water adjuvant ISA 201 VG and an aqueous polymeric adjuvant Montanide
      Gel 01. Vaccinations with these three adjuvants did not produce severe general
      reaction but an increase in skin thickness was observed especially with both oil
      based emulsions. These results indicated that the water-in-oil adjuvant is the
      most interesting to use for this vaccine but local adverse reactions remain an
      issue.

PMID- 28752481
TI  - Complexity, adaptations and variations in the secondary insemination system of
      female Dermanyssina mites (Acari: Anactinothrichida: Gamasida): the case of
      Afrocypholaelaps africana.
AB  - Gamasine mites, mainly of the taxon Dermanyssina, possess a secondarily evolved
      insemination system (sperm access system), of which there are two, generally
      recognized, structurally different types, the laelapid- and the phytoseiid-type.
      The ultrastructure of the female sperm access system in Afrocypholaelaps africana
      is described. It consists of paired insemination pores, opening between the bases
      of legs three and four, and paired cuticle-lined tubules that converge into a
      large, sack-like spermatheca, remarkably cuticle-lined as well. The entire
      spermatheca and part of the tubules are embedded in a peculiar syncytial tissue
      where numerous sperm cells are present. The general organization of this
      insemination system is of the laelapid-type. However, it presents striking
      structural differences, compared with the systems described in Varroa destructor
      and Hattena cometis, the other gamasine mites having a laelapid-type system
      studied ultrastructurally until now. The functional morphology, complexity and
      variations of the sperm access system in Dermanyssina are discussed and
      correlated with the evolutionary biology of the group.

PMID- 28752482
TI  - Is body size important? Seasonal changes in morphology in two grass-feeding
      Abacarus mites.
AB  - Overwintering strategies in herbivorous mites (Acariformes: Eriophyoidea) are
      poorly understood. A study of two Abacarus spp. was conducted to compare body
      size parameters of adult females in different seasons. Mites of Abacarus n. sp.
      (under description) and A. lolli were sampled from Bromopsis inermis and Lolium
      perenne, respectively, in April, September and December of 2001 in Poznan,
      Poland; 21 morphological traits were measured for each specimen. A principal
      component analysis revealed significant differences in body size parameters
      between collection dates, with larger females collected in December in both
      species. Larger body size in winter is consistent with the hypothesis that mites
      of these species, for which deutogyny has not been observed, undergo
      physiological changes such as accumulation of nutritional reserves, that enable
      them to withstand adverse environmental conditions. Larger body size has also
      been shown in other invertebrates to reduce heat loss in cold conditions. Filling
      gaps in the current knowledge of eriophyoid overwintering strategies, whether in
      the presence or absence of deutogyny, will contribute to both basic and applied
      future studies of this important arthropod group.

PMID- 28752483
TI  - Testing of Anesthesia Machines and Defibrillators in Healthcare Institutions.
AB  - To improve the quality of patient treatment by improving the functionality of
      medical devices in healthcare institutions. To present the results of the safety
      and performance inspection of patient-relevant output parameters of anesthesia
      machines and defibrillators defined by legal metrology. This study covered 130
      anesthesia machines and 161 defibrillators used in public and private healthcare
      institutions, during a period of two years. Testing procedures were carried out
      according to international standards and legal metrology legislative procedures
      in Bosnia and Herzegovina. The results show that in 13.84% of tested anesthesia
      machine and 14.91% of defibrillators device performance is not in accordance with
      requirements and should either have its results be verified, or the device
      removed from use or scheduled for corrective maintenance. Research emphasizes
      importance of independent safety and performance inspections, and gives
      recommendations for the frequency of inspection based on measurements. Results
      offer implications for adequacy of preventive and corrective maintenance
      performed in healthcare institutions. Based on collected data, the first digital
      electronical database of anesthesia machines and defibrillators used in
      healthcare institutions in Bosnia and Herzegovina is created. This database is a
      useful tool for tracking each device's performance over time.

PMID- 28752484
TI  - Composite Pheochromocytoma/Paraganglioma-Ganglioneuroma: A Clinicopathologic
      Study of Eight Cases with Analysis of Succinate Dehydrogenase.
AB  - Ganglioneuromas represent the most well-differentiated spectrum of neoplasia
      arising from the sympathetic nervous system, while neuroblastomas represent the
      most poorly differentiated counterpart, and ganglioneuroblastomas represent
      intermediate stages of differentiation. Small series of cases have documented the
      co-occurrence of ganglioneuroma with a pheochromocytoma (Pheo)/paraganglioma
      (PGL) component. We report the clinicopathologic features of eight such cases,
      diagnosed between 2003 and 2015 with a mean follow-up of 22 months (1-47), which
      were evaluated for syndrome associations, SDHB expression, and clinical outcome.
      Mutations of the succinate dehydrogenase (SDH) complex subunits (A, B, C, D, and
      SDHAF2) have been implicated in predicting metastatic behavior and in identifying
      possible paraganglioma syndromes. The proliferative index was calculated by
      manual quantification of Ki-67-positive cells at selected hot-spots using ImageJ
      (NIH). In our series, composite Pheo/PGL-ganglioneuromas predominantly involved
      the adrenal gland (Pheo 7, PGL 1). The cases had an equal gender distribution
      (males 4, females 4), with a mean age at diagnosis of 67 years (range 53 to 86
      years), an average size of 5.2 cm (range 2 to 8.2 cm), an average weight of 49.3
      g (7.8 to 144.7 g, n = 6), and the majority were functionally active (7 of 8,
      88%). The mean Ki67 proliferation rate was 2% (range 0.3 to 3%), and all cases
      retained SDHB expression (8/8, 100%). No patient (0/8, 0%) developed metastatic
      disease on follow-up. One patient had a retroperitoneal composite PGL
      ganglioneuroma in the setting of neurofibromatosis type 1. No recurrent disease
      or other associations were identified. In our study, composite Pheo/PGL
      ganglioneuromas predominantly affected the adrenal gland in older patients,
      showed no loss of SDHB, and no disease recurrence was identified.

PMID- 28752485
TI  - Effect of Aggregation on the Hydrodynamic Properties of Bovine Serum Albumin.
AB  - PURPOSE: To systematically analyze shape and size of soluble irreversible
      aggregates and the effect of aggregate formation on viscosity. METHODS: Online
      light scattering, refractive index and viscosity detectors attached to HPLC
      (Viscotek(r)) were used to study aggregation, molecular weight and intrinsic
      viscosity of bovine serum albumin (BSA). Irreversible aggregates were generated
      by heat stress. Bulk viscosity was measured by an oscillating piston viscometer.
      RESULTS: As BSA was heated at a higher concentration or for a longer time, the
      relative contribution, molecular weight and intrinsic viscosity of aggregate
      species increased. Molecular shape was evaluated from intrinsic viscosity values,
      and aggregates were estimated to be more asymmetric than monomer species. The
      presence of aggregates resulted in an increase in bulk viscosity when relative
      contribution of very high molecular weight species exceeded 10%. CONCLUSIONS: For
      model system and conditions studied, generation of higher order aggregate species
      was concluded to be associated with an increase in molecular asymmetry. Elevated
      viscosity in the presence of aggregated species points to molecular asymmetry
      being a critical parameter affecting solution viscosity of BSA.

PMID- 28752486
TI  - Ecological Instability and Children's Classroom Behavior in Kindergarten.
AB  - We engage the concept of ecological instability to assess whether children's
      exposure to frequent change in multiple contexts is associated with teacher
      reports of students' overall behavior, externalizing behavior, and approach to
      learning during kindergarten. We operationalize multiple dimensions of children's
      exposure to repeated change-including the frequency, concurrency, chronicity,
      timing, and types of changes children experience-in a nationally representative
      longitudinal cohort of U.S.-born children (Early Childhood Longitudinal Study
      Birth Cohort, N ~ 4,750). We focus on early childhood, a period of substantial
      flux in children's family and neighborhood contexts. Predicted behavior scores
      differ by approximately one-fifth of a standard deviation for children who
      experienced high or chronic exposure to ecological change compared with those who
      experienced little or no change. These findings emphasize the distinctiveness of
      multidomain ecological instability as a risk factor for healthy development that
      should be conceptualized differently from the broader concept of normative levels
      of change in early childhood environments.

PMID- 28752487
TI  - The Demography of Mental Health Among Mature Adults in a Low-Income, High-HIV
      Prevalence Context.
AB  - Very few studies have investigated mental health in sub-Saharan Africa (SSA).
      Using data from Malawi, this article provides a first picture of the demography
      of depression and anxiety (DA) among mature adults (aged 45 or older) in a low
      income country with high HIV prevalence. DA are more frequent among women than
      men, and individuals affected by one are often affected by the other. DA are
      associated with adverse outcomes, such as poorer nutrition intake and reduced
      work efforts. DA also increase substantially with age, and mature adults can
      expect to spend a substantial fraction of their remaining lifetime-for instance,
      52 % for a 55-year-old woman-affected by DA. The positive age gradients of DA are
      not due to cohort effects, and they are in sharp contrast to the age pattern of
      mental health that has been shown in high-income contexts, where older
      individuals often experience lower levels of DA. Although socioeconomic and risk-
      or uncertainty-related stressors are strongly associated with DA, they do not
      explain the positive age gradients and gender gap in DA. Stressors related to
      physical health, however, do. Hence, our analyses suggest that the general
      decline of physical health with age is the key driver of the rise of DA with age
      in this low-income SSA context.

PMID- 28752488
TI  - Wnt/beta-catenin Signaling in Osteoarthritis and in Other Forms of Arthritis.
AB  - PURPOSE OF REVIEW: Arthritis defines a large group of diseases primarily
      affecting the joint. It is the leading cause of pain and disability in adults.
      Osteoarthritis (OA) affecting the knee or hip is the most common form among over
      100 types of arthritis. Other types of arthritis include erosive hand OA,
      temporomandibular joint (TMJ) OA, facet joint OA, diffuse idiopathic skeletal
      hyperostosis (DISH), and spondyloarthritis (SpA). However, the specific molecular
      signals involved in the development and progression of OA and related forms of
      arthritis remain largely unknown. The canonical wingless/integrated (Wnt)/beta
      catenin signaling pathway could play a unique role in the pathogenesis of
      arthritis. In this review article, we will focus on the molecular mechanisms of
      Wnt/beta-catenin signaling in the pathogenesis of OA and other types of
      arthritis. RECENT FINDINGS: Emerging evidence demonstrates that Wnts and Wnt
      related molecules are involved in arthritis development and progression in human
      genetic studies and in vitro studies. Also, mouse models have been generated to
      determine the role of Wnt/beta-catenin signaling in the pathogenesis of
      arthritis. Wnt/beta-catenin signaling represents a unique signaling pathway
      regulating arthritis development and progression, and the molecules in this
      particular pathway may serve as targets for the therapeutic intervention of
      arthritis. Mediators and downstream effectors of Wnt/beta-catenin signaling are
      increased in OA as well other forms of arthritis, including DISH and SpA. Through
      extensive investigations, including pre-clinical studies in transgenic mice and
      translational and human studies, the Wnt/beta-catenin signaling pathway has been
      proven to play roles in bone and joint pathology by directly affecting bone,
      cartilage, and synovial tissue; further, these pathologies can be reduced through
      targeting this pathway. Continued investigation into the distinct molecular
      signaling of the Wnt/beta-catenin pathway will provide additional insights toward
      the therapeutic intervention in arthritis.

PMID- 28752489
TI  - Mechanism of New Bone Formation in Axial Spondyloarthritis.
AB  - PURPOSE OF THE REVIEW: The purpose of this review is to discuss new evidence
      explaining the progress from bony inflammation over repair tissue to new bone
      formation in axial spondyloartrhitis and its correlations in imaging and
      histology of the bone. RECENT FINDINGS: Data from imaging, histology and
      treatment interventions indicates that the disease starts with inflammation,
      followed by replacement of subchondral bone marrow by repair tissue which
      presence is crucial for the stimulation of new bone formation. The magnetic
      resonance imaging (MRI) sequences of STIR and T1 are currently the most commonly
      used imaging techniques to follow this process; explanations are offered for the
      limited sensitivity to detect these bony changes on MRI in their different
      phases. Early and effective anti-inflammatory treatment is crucial for the
      prevention of long-term ankylosis. Whether there are currently also treatment
      options targeting new bone formation in these patients directly is less clear.

PMID- 28752490
TI  - Do Biologic Therapies for Rheumatoid Arthritis Offset Treatment-Related Resource
      Utilization and Cost? A Review of the Literature and an Instrumental Variable
      Analysis.
AB  - PURPOSE OF REVIEW: One justification for using expensive biologic therapy in
      rheumatoid arthritis (RA) has been that it can reduce future healthcare
      utilization such as joint surgeries and physician visits. However, the evidence
      to support this assertion is unclear. We conducted a review of the literature for
      studies which have analyzed the trends in resource use of RA patients, and then
      undertook a retrospective observational analysis of a Canadian administrative
      database using instrumental variable methods. RECENT FINDINGS: Our review found a
      trend in reduced resource utilization prior to the introduction of biologics and
      no evidence that biologic therapies have specifically contributed to this
      reduction. Our observational analysis, which overcame some of the epidemiological
      challenges with determining the influence of biologics on resource utilization,
      found a possible reduction in other medications but possible increases rather
      than decreases in physician visits and hospitalizations. However, our sample was
      not sufficiently large to make definitive conclusions. Over 15 years since the
      introduction of biologics for RA, no evidence exists supporting the assumption
      that biologic therapies reduce future healthcare utilization. While such a
      question is challenging to generate evidence for, and so an absence of evidence
      does not suggest that the hypothesis is incorrect, an instrumental variable
      analysis using sufficient data could provide definitive evidence.

PMID- 28752491
TI  - Predictors of Osteoarthritis Pain: the Importance of Resilience.
AB  - PURPOSE OF REVIEW: Osteoarthritis (OA) is one of the most common and disabling
      forms of arthritis worldwide, with joint pain being a primary symptom. Given that
      clinical symptoms often show poor concordance with tissue damage in OA, processes
      other than joint remodeling likely play a role in the condition. Using the
      biopsychosocial model of pain as a guiding framework, the purpose of this review
      is to highlight the extra-articular mechanisms that contribute to pain and
      dysfunction in OA, with a specific focus on resilience. RECENT FINDINGS: Whereas
      previous research has mostly focused on risk factors for worsening of OA pain,
      recently emerging evidence places greater emphasis on the identification of
      protective mechanisms that enhance pain adaptation and palliate the negative
      effects of joint pain. In view of this new and important research, more emphasis
      should be placed on endogenous pain modulation and, in particular, pain
      attenuation. The result of such work could serve as a basis for optimizing
      treatment in the OA population.

PMID- 28752492
TI  - Pulmonary Involvement in Systemic Vasculitis.
AB  - PURPOSE OF REVIEW: The purpose of this study is to describe the most relevant
      advances concerning lung involvement in the ANCA-associated vasculitides
      (excluding eosinophilic granulomatosis with polyangiitis which may have different
      disease mechanisms). Focus is on pathophysiology, recent important imagenological
      procedures, treatment, and outcome. RECENT FINDINGS: Emerging information exists
      on potential newly investigated diagnostic procedures (v.g. transbronchial
      cryobiopsies), detailed tomographic abnormalities, the potential favorable role
      of rituximab and the still uncertain one of plasma exchange in the treatment, and
      the increasing description of interstitial lung disease. Survival is reduced in
      case of both, diffuse alveolar hemorrhage and diffuse parenchymal disease. There
      is the need to expand the knowledge concerning better long-term treatment options
      with specific regimes, and to incorporate other measures regarding integral
      treatment in patients afflicted with lung involvement these maladies, as the
      outcome seems adverse in this scenario.

PMID- 28752493
TI  - Mindfulness Meditation for Fibromyalgia: Mechanistic and Clinical Considerations.
AB  - PURPOSE OF REVIEW: Fibromyalgia is a disorder characterized by widespread pain
      and a spectrum of psychological comorbidities, rendering treatment difficult and
      often a financial burden. Fibromyalgia is a complicated chronic pain condition
      that requires a multimodal therapeutic approach to optimize treatment efficacy.
      Thus, it has been postulated that mind-body techniques may prove fruitful in
      treating fibromyalgia. Mindfulness meditation, a behavioral technique premised on
      non-reactive sensory awareness, attenuates pain and improves mental health
      outcomes. However, the impact of mindfulness meditation on fibromyalgia-related
      outcomes has not been comprehensively characterized. The present review
      delineates the existing evidence supporting the effectiveness and hypothesized
      mechanisms of mindfulness meditation in treating fibromyalgia-related outcomes.
      RECENT FINDINGS: Mindfulness-based interventions premised on cultivating
      acceptance, non-attachment, and social engagement may be most effective in
      decreasing fibromyalgia-related pain and psychological symptoms. Mindfulness
      based therapies may alleviate fibromyalgia-related outcomes through multiple
      neural, psychological, and physiological processes. Mindfulness meditation may
      provide an effective complementary treatment approach for fibromyalgia patients,
      especially when combined with other reliable techniques (exercise; cognitive
      behavioral therapy). However, characterizing the specific analgesic mechanisms
      supporting mindfulness meditation is a critical step to fostering the clinical
      validity of this technique. Identification of the specific analgesic mechanisms
      supporting mindfulness-based pain relief could be utilized to better design
      behavioral interventions to specifically target fibromyalgia-related outcomes.

PMID- 28752495
TI  - Changing clinical phenotypes of HIV-associated neurocognitive disorders.
AB  - HIV-associated neurocognitive disorder (HAND) remains a common cause of cognitive
      impairment and persists in 15-55% of HIV+ individuals in the combination
      antiretroviral therapy (CART) era. CART is now the primary treatment for HAND,
      but it is effective in only a subset of patients. In the pre-CART era, HIV
      associated dementia was the most common form of HAND. However, in CART-treated
      patients, the prevalence of HIV-associated dementia has declined substantially,
      and milder stages of HAND, i.e., ANI and MND predominate. HIV+ patients with mild
      neurocognitive disorder (MND) can still have significant functional impairment in
      some activities of daily living. There have been several other significant
      changes in the clinical features of HAND in the CART era. The mean survival for
      an individual diagnosed with HIV dementia has increased dramatically. In HIV+
      individuals on CART with a suppressed systemic viral load, the majority of
      individuals with HAND remain stable, with a small proportion showing
      deterioration. Extrapyramidal signs are now less common in patients with HAND on
      CART. In the CART era, HAND may have a mixed pattern of both cortical and
      subcortical features with greater deficits in executive functioning and working
      memory. Despite the milder clinical phenotype, in the CART era, patients with
      HAND still have persistent laboratory and neuroimaging abnormalities in the
      central nervous system even with systemic viral suppression. As the HIV+ patient
      population ages, cerebrovascular disease risk factors such as hypertension,
      diabetes, and hypercholesterolemia are increasingly recognized as risk factors
      for cognitive impairment in HIV+ patients on CART. HAND remains a common
      neurological condition globally in the CART era, necessitating the need for new
      animal models to examine pathogenesis and potential treatments for HAND.

PMID- 28752494
TI  - Epigenetics in SLE.
AB  - PURPOSE OF REVIEW: Systemic lupus erythematosus is a severe
      autoimmune/inflammatory condition of unknown pathophysiology. Though genetic
      predisposition is essential for disease expression, risk alleles in single genes
      are usually insufficient to confer disease. Epigenetic dysregulation has been
      suggested as the missing link between genetic risk and the development of
      clinically evident disease. RECENT FINDINGS: Over the past decade, epigenetic
      events moved into the focus of research targeting the molecular pathophysiology
      of SLE. Epigenetic alteration can be the net result of preceding infections,
      medication, diet, and/or other environmental influences. While altered DNA
      methylation and histone modifications had already been established as
      pathomechanisms, DNA hydroxymethylation was more recently identified as an
      activating epigenetic mark. Defective epigenetic control contributes to
      uncontrolled cytokine and co-receptor expression, resulting in immune activation
      and tissue damage in SLE. Epigenetic alterations promise potential as disease
      biomarkers and/or future therapeutic targets in SLE and other
      autoimmune/inflammatory conditions.

PMID- 28752496
TI  - Investigations on in vitro anti-carcinogenic potential of L-carnosine in liver
      cancer cells.
AB  - This study was carried out to investigate the anti-carcinogenic effect of L
      carnosine in human carcinoma cells (SNU-423). The SNU-423 cancer cells were
      cultured at a density of 2 * 104 cells/well in Dulbecco modified Eagle medium.
      After 24 h of adherence, the cells were treated with L-carnosine (0.2 and 1
      mg/mL) for 48 h. Then, cell viability was assessed by sulforhodamine assay, while
      mitochondrial dysfunction was measured by fluorescence microscopy using chromatin
      specific dye Hoechst 33258. Intracellular levels of ROS were assayed by
      fluorescence spectroscopy with 2',7'-dichlorofluorescein diacetate (DCFDA). L
      Carnosine significantly inhibited the growth of the SNU-423 cells (p < 0.05). The
      inhibitory effect of L-carnosine was confirmed by results from mitochondrial
      fragmentation assay. The relative fluorescent unit was increased in a dose
      dependent manner by L-carnosine, with values of 79.43, 186.87 and 400.89 for 0.6,
      0.8 and 1 mg/mL of L-carnosine, respectively (p < 0.05). These results
      demonstrate that L-carnosine exerts anti-carcinogenic effects in human liver
      cancer cells.

PMID- 28752497
TI  - Testing virtual reality-based cue-exposure software: Which cue-elicited responses
      best discriminate between patients with eating disorders and healthy controls?
AB  - PURPOSE: Virtual reality (VR) technologies have been proposed as a new tool able
      to improve on in vivo exposure in patients with eating disorders. This study
      assessed the validity of a VR-based software for cue exposure therapy (CET) in
      people with bulimia nervosa (BN) and binge eating disorder (BED). METHODS: Fifty
      eight outpatients (33 BN and 25 BED) and 135 healthy participants were exposed to
      10 craved virtual foods and a neutral cue in four experimental virtual
      environments (kitchen, dining room, bedroom, and cafeteria). After exposure to
      each VR scenario, food craving and anxiety were assessed. The frequency/severity
      of episodes of uncontrollable overeating was also assessed and body mass index
      was measured prior to the exposure. RESULTS: In both groups, craving and anxiety
      responses when exposed to the food-related virtual environments were
      significantly higher than in the neutral-cue virtual environment. However,
      craving and anxiety levels were higher in the clinical group. Furthermore, cue
      elicited anxiety was better at discriminating between clinical and healthy groups
      than cue-elicited craving. CONCLUSIONS: This study provides evidence of the
      ability of food-related VR environments to provoke food craving and anxiety
      responses in BN and BED patients and highlights the need to consider both
      responses during treatment. The results support the use of VR-CET in the
      treatment of eating disorder patients characterized by binge-eating and people
      with high bulimic symptoms.

PMID- 28752498
TI  - Pseudoprogression in pediatric low-grade glioma after irradiation.
AB  - This study aimed to assess the incidence and management of pseudoprogression
      after radiation therapy (RT) in patients with pediatric low-grade glioma (LGG).
      This retrospective review included patients aged 21 years or younger with
      intracranial LGG treated with curative-intent RT. Pseudoprogression was defined
      as an increase in tumor size by >=10% in at least two dimensions between two and
      three consecutive MR imaging studies. Overall survival (OS) and event-free
      survival (EFS) were measured from the first day of RT. EFS was defined as
      survival without true progression or secondary high-grade glioma. Sixty-two of
      221 patients developed pseudoprogression, with a 10-year cumulative incidence of
      29.0% (95% CI 23.0-35.2). Median time to pseudoprogression was 6.1 months after
      RT. Symptomatic pseudoprogression was managed with subtotal resection,
      shunt/Ommaya reservoir placement, or corticosteroids in 11 (18%), 7 (11%), and 2
      patients (3%), respectively. The remaining tumors were observed (68%). Patients
      with pilocytic astrocytoma (PA) had 5.4-fold greater odds of developing
      pseudoprogression relative to tumors of other histology (odds ratio 95% CI 2.5
      11.4, P < 0.0001). Among patients with PA (n = 127), the 10-year cumulative
      incidence of pseudoprogression was 42.9%. In this group, pseudoprogression was
      associated with improved 10-year EFS (84.5% vs. 58.5%, P = 0.008) and OS (98.0%
      vs. 91.2%, P = 0.03). Pseudoprogression after irradiation was common, especially
      in patients with pilocytic astrocytoma, and was associated with improved
      survival. Knowledge of the incidence and temporal course of pseudoprogression may
      help avoid unnecessary salvage therapy.

PMID- 28752499
TI  - Walking ability in patients with glioblastoma: prognostic value of the Berg
      Balance Scale and the 10 meter walk test.
AB  - Primary brain tumors frequently cause considerable functional impairments and the
      survival time when diagnosed with glioblastoma is 14.6 months. The aim of this
      study was to examine if baseline postural control and walking ability in patients
      with glioblastoma could predict long term walking ability and 1 year mortality.
      Data were gathered from prospective recordings in a brain cancer database
      supplemented by retrospective review of electronic patient records. We included
      109 patients with glioblastoma, 47 women and 62 men with mean age 65 years. At
      admission 84 patients were tested with Berg Balance Scale and 57 were tested with
      10 meter walk test. Binary logistic regression analysis showed no statistical
      significance in favour of the 10 meter walk test. Berg Balance Scale showed an
      ability to predict walking ability 4-8 months after admission. The risk of dying
      within a year was 6.9 times higher in patients who lost their ability to walk
      within 4-8 months of the first admission. This study showed that Berg Balance
      Scale has some ability to predict the loss of walking ability 4-8 months after
      admission. This could be an important indicator pin pointing patients most in
      need of more intensive specialized neurorehabilitation efforts early in the
      disease course.

PMID- 28752500
TI  - Negative impact of leukoaraiosis on the incidence of brain metastases in patients
      with lung cancer.
AB  - The embolization of cancer cells to cerebral vessels occurs early in the multi
      step metastatic process. We aimed to determine whether the presence of
      leukoaraiosis (LA) before treatment would predict the development of brain
      metastases (BM) in patients with lung cancer. Between January 2014 and June 2015,
      1007 patients underwent initial (i.e., prior to any chemotherapy) or routine
      magnetic resonance (MR) imaging of the brain and exhibited no evidence of BM. Of
      these, 189 underwent repeat MR imaging; 34 of 189 patients (18%) developed new
      BM, whereas 155 patients did not. LA was retrospectively evaluated according to
      Fazekas scale on the initial screening MR images of these 189 patients. The
      frequency of grade 0 periventricular hyperintensity (PVH) was greater among
      patients with BM, compared to those without BM (p = 0.001). In a multivariate
      analysis, patients with adenocarcinoma (95% confidence interval [CI] 1.8-171.8)
      and small cell carcinoma (95% CI 1.4-172.4) respectively developed BM at 9.3- and
      8.8-fold higher rates than those with squamous cell carcinoma. Patients with
      grade 0 PVH developed BM at a rate 3.5-, 8.6-, and 3.6-fold higher rates than
      those with grade 1 (95% CI 1.4-9.0), 2 (95% CI 2.4-41.9), and 3 (95% CI 1.02
      15.0), respectively. Lung cancer patients with grade 0 PVH on initial MR images
      have a high subsequent incidence of BM. PVH is a useful method for evaluating
      risk of BM.

PMID- 28752501
TI  - Prognostic value of ion channel genes in Chinese patients with gliomas based on
      mRNA expression profiling.
AB  - Increasing evidence suggests that ion channels not only regulate electric
      signaling in excitable cells but also play important roles in the development of
      human cancer. However, the roles of ion channels in glioma remain controversial.
      We systematically analyzed the expression patterns of ion channel genes in a
      cohort of Chinese patients with glioma using whole-genome mRNA expression
      profiling. First, a molecular signature comprising 47 ion channel genes (IC47)
      was identified using Spearman's rank correlation test conducted between tumor
      grade and gene expression. We assigned a risk score based on IC47 to each glioma
      patient. We demonstrated that the risk score effectively predicted overall
      survival in glioma patients. Next, we screened IC47 in different molecular glioma
      subtypes. IC47 showed a Mesenchymal subtype and wild-type IDH1 preference. Gene
      ontology (GO) analysis and gene set variation analysis (GSVA) for the functional
      annotation of IC47 showed that patients with high-risk scores tended to exhibit
      the decreased expression of proteins associated with the apoptosis and cell
      adhesion, and higher expression of proteins associated with the cell cycle and
      cell proliferation. These results suggest that ion channel gene expression could
      improve the subtype classification in gliomas at the molecular level. The
      findings in the present study have been validated in two independent cohorts.

PMID- 28752502
TI  - Attitude of patients, healthcare professionals, and noninjured lay persons
      towards online video instructions on mild traumatic brain injury: a cross
      sectional study.
AB  - BACKGROUND: The objective of this study was to determine the attitude of
      patients, healthcare professionals, and noninjured lay persons towards adding a
      video with discharge instructions to patient care for patients with mild
      traumatic brain injury (MTBI). A survey was conducted at the emergency department
      (ED). Participants consisted of MTBI patients (n = 50), healthcare professionals
      (n = 50), and noninjured lay persons (n = 50). The participants viewed a video
      with discharge instructions on MTBI and filled out a questionnaire that measured
      their attitude towards the use of a video as part of discharge instructions.
      FINDINGS: Nearly all healthcare professionals (94%) and 70% of the noninjured lay
      persons considered the video to be a valuable addition to oral discharge
      instructions. For 84% of patients, verbal information from the doctor is of
      importance. And, 50% of patients would like to receive additional video discharge
      instructions. CONCLUSIONS: The majority of noninjured lay persons and healthcare
      professionals and half of the MTBI patients consider a video with discharge
      instructions to be a valuable addition to patient care. Video discharge
      instructions are a relative low-cost measure that could enhance patient care at
      the ED, provided that this does not compromise the personal contact between
      patient and healthcare professional.

PMID- 28752503
TI  - Trends in Drug Prescription Rates for Dementia: An Observational Population-Based
      Study in France, 2006-2014.
AB  - BACKGROUND: Since the 2011 French guidance updates, cholinesterase inhibitors and
      memantine are considered optional in the management of dementia and leave
      physicians free to prescribe based on their clinical expertise. OBJECTIVES: The
      aims of this study were to analyze the influence of these recent guidance updates
      on the prescription rates of these drugs and to quantify the impact of potential
      changes on healthcare expenditures. METHODS: Patients over 65 years old from a
      representative sample of a national administrative claims database, the French
      national health insurance database, were retrospectively included from 2006 to
      2014. Trends of annual prescription rates were tested using adjusted segmented
      regression analysis. Drug costs with and without prescribers' behavioral changes
      were estimated. RESULTS: A total of 119,731 individuals were included and
      followed during the study period. Among them, 5514 individuals were treated for
      dementia. According to the unadjusted segmented regression model, there was a
      significant increase in prescription rates between 2006 and 2010, from 2.23% (95%
      confidence interval 2.13-2.34) to 2.73% (95% confidence interval 2.62-2.84) of
      the study population. Since 2011, the trend has reversed with a significant
      decrease until 2014, from 2.64% (95% confidence interval 2.54-2.75) to 1.92% (95%
      confidence interval 1.84-2.01). In the multivariate analysis, we also found a
      gradual decline since 2011, particularly for patients aged 65-69 years and with
      one or more other chronic diseases. Cost savings associated with prescribers'
      behavioral changes were estimated at ?108 million. CONCLUSION: Drugs prescribed
      for dementia are on a declining trend with important cost savings, and this was
      concomitant with guidance updates that left physicians to rely on their clinical
      expertise while managing dementia.

PMID- 28752504
TI  - ?
AB  - Crohn?s disease (CD) is a chronic inflammatory bowel disease whose oral features
      remain underrated at clinical examination. The aim of the study was to report
      forerunner orofacial presentations leading to diagnosis of CD among nine patients
      of mean age 23 between 2008 and 2015. Linear ulcerative buccal lesions,
      cobblestoning, mucosal tags and perioral erythema are highly evocative and might
      precede intestinal signs for several years. Oral biopsies revealed highly
      suggestive lesions of CD for 45% of patients before any intestinal symptom or
      digestive investigation. Mean time to diagnosis was 14 months. Immunomodulatory
      therapy (azathioprine, infliximab, adalimumab) was introduced alone or in
      association for 89% of patients. Early diagnosis could lead to specific therapy,
      often necessary to reduce severity of lesions and improve quality of life.

PMID- 28752505
TI  - ?
AB  - This script gives a pragmatic advice for general dentists on accurate use of
      amoxicillin with clavulanic acid considering current literature at acute
      inflammatory disease. In absence of contraindications a twice daily formulation
      of 1g amoxicillin with clavulanic acid is the first choice for concomitant
      therapy after treating the cause of inflammation or prophylaxis. Compared to
      clindamycin the concentration of amoxicillin in teeth and bone (Hallig 2014) is
      higher and has less gastrointestinal side-effects (Bax 2007). Furthermore it is
      prescribable during pregnancy and lactation. With these advantages amoxicillin
      with clavulanic acid is the first choice of antibiotics in general dental
      medicine.

PMID- 28752506
TI  - Dental tourism from Switzerland to Germany.
AB  - In recent years the topic of dental tourism has increasingly come into focus of
      dentists and patients. In the present study an attempt was made to find out, why
      patients from a restricted region travel to Germany for dental care. In five
      German dental clinics located in the border area between Switzerland and Germany,
      272 women and 236 men ranging in age from 5 to 94 years, who had undergone at
      least one dental treatment in Germany, were questioned concerning the reasons for
      their visits. The interviews took place within a period of 6 months and relied on
      a questionnaire to collect data regarding sociodemographic features and patient
      behavior. In comparison to residents of Germany, patients residing in Switzerland
      took on considerably longer travel distances for the dental visit, in some cases
      more than 50km (9.7%). For patients residing in Switzerland the technical
      equipment of the practice was more important (p<0.001), whereas for residents of
      Germany the cost-effective treatment was decisive (p<0.05). Almost all patients
      residing in Switzerland (95.6%) confirmed that dental treatments in Germany were
      cheaper and that additional family members also came to Germany for dental care
      (65.0%).

PMID- 28752507
TI  - Intravenous Alteplase for Acute Ischemic Stroke in Taiwan: Can We Expand the
      National Health Insurance's Reimbursement Criteria?
AB  - lization of intravenous thrombolysis with alteplase was very low in Taiwanese
      patients with acute ischemic stroke(1). One of the reasons is the strict
      reimbursement guideline made by the Bureau of National Health Insurance (NHI) in
      2004(2). In this issue of the Acta Neurologica Taiwanica, Yu-Hsiang Su and co
      authors(3) retrospectively evaluated outcomes of their thrombolysed stroke
      patients who were "mismatched" between updated clinical practice guideline and
      NHI reimbursement criteria. They concluded that the outcomes of patients treated
      according to guidelines were comparable between the reimbursement and non
      reimbursement groups. Despite the inherent selection bias and no comparison with
      the non-treated patients in this observational study, it might serve the an
      important local evidence for physicians in Taiwan when evaluating intravenous
      thrombolysis for acute ischemic stroke. SO, CAN WE EXPAND THE REIMBURSEMENT
      CRITERIA FOR INTRAVENOUS ALTEPLASE IN STROKE PATIENTS? At the present time, the
      answer may still probably be NO! The insurance payer, usually after an economic
      evaluation, may decide to pay a pharmaceutical product for its beneficiaries. As
      a rule of thumb, insurance reimbursement criteria should not be greater than the
      labelled prescribing information. Thus, the essence of this question should be
      back to the labelled indications and contraindications of alteplase for stroke,
      made by Taiwanese regulator in Nov 2002(4). Although data from high-quality meta
      analyses(5,6) of new trials in the past decade challenged some of the major
      contraindications, such as onset > 3 hours or age > 80 years, the Taiwan's Food
      and Drug Administration has turned down twice the application by the manufacturer
      to change the package insert regarding those two contraindications. The reasons
      were mostly "insufficient of benefits". Without the change of labelled
      prescribing information, the NHI reimbursement criteria cannot be expanded. WHAT
      CAN WE DO NOW? Pragmatically, physicians should consider the potential
      medicolegal consequences if the potentially lethal symptomatic intracranial
      hemorrhage occur after such "off-label" uses of alteplase in their stroke
      patients. The problems may get even worse if the fee of alteplase is paid with
      patients' out-of-pocket money. Nevertheless, the potential solution of this issue
      may be still medical technology and stroke science themselves. For stroke
      patients not eligible for intravenous thrombolysis at present time, the use of
      endovascular therapy (EVT) or screening for the eligibility of ongoing clinical
      trials might be considered. In Jan 2016, three novel devices for EVT in stroke
      patients with large vessel occlusion got reimbursement by Taiwan's NHI(7). The
      reimbursement criteria were much wider than intravenous alteplase, e.g., the time
      window may be as long as 8 hours for an anterior circulation stroke, and there's
      no upper limit of age. And for those with unclear onset time of stroke (e.g. the
      "wake-up stroke"), screening with modern imaging technique for penumbra and
      determining the eligibility of large multicenter randomized thrombolysis trials
      may be another option(8,9). Administrating intravenous thrombolysis under the
      setting of a wellconducted clinical trial in patients not eligible according to
      current labelled indication should be more appropriate than the previous "off
      label" practice pattern. It is not only safer medicolegally and ethically for the
      patients and physicians, but also provides more solid evidences to change or
      generate new label indications of thrombolysis for stroke patients in the future.
      In conclusion, the non-reimbursement group in Su, et al(3). is a mixture of
      stroke patients with very heterogeneous characteristics. With the advances of
      imaging selection modalities and new hyperacute treatment options nowadays, they
      should no longer be considered as an identical group of patients. We
      strokologists, as an emerging subspecialists, should devote more in dedicated and
      individualized selection of stroke patients for appropriate early recanalization
      therapy to improve their outcomes. Conflict of Interest Disclosure: I received
      speaker fee from Boehringer Ingelheim for Actilyse(r)
      (http://grsp2013.innovarad.tw/2016/07/rt-pa_ forum_hsiehcy_share.html).
      Acknowledgements: I thank Dr. Chan-Shan Chen for his critical review of this
      manuscript.

PMID- 28752508
TI  - Safety and Effectiveness of Intravenous Thrombolysis for Acute Ischemic Stroke
      Outside the Coverage of National Health Insurance in Taiwan.
AB  - PURPOSE: Only a small percentage of ischemic stroke patients were treated with
      intravenous thrombolysis in Taiwan, partly because of the narrow reimbursement
      criteria of the National Health Insurance (NHI). We aimed to assess the safety
      and effectiveness of intravenous thrombolysis not covered by the NHI. METHODS:
      This is a retrospective analysis of register data from four hospitals. All
      patients who received intravenous tissue plasminogen activator and fulfilled the
      American Heart Association/American Stroke Association (AHA/ASA) thrombolysis
      guidelines between January 2007 and June 2012 were distinguished into two groups:
      those in accordance (reimbursement group) and those not in accordance (non
      reimbursement group) with the NHI reimbursement criteria. Primary outcome was
      symptomatic intracerebral hemorrhage (SICH). Secondary outcomes were dramatic
      improvement in the National Institutes of Health Stroke Scale (NIHSS) score at
      discharge, good functional outcome (modified Rankin Scale <=2) at discharge, and
      all-cause in-hospital mortality. RESULTS: In 569 guideline-eligible patients, 177
      (31%) were treated without reimbursement. The reasons for exclusion from
      reimbursement included age >80 (n=42), baseline NIHSS less than 6 (n=29),
      baseline NIHSS >25 (n=15), thrombolysis beyond 3 hours (n=49), prior stroke with
      diabetes (n=28), use of oral anticoagulant (n=2), and more than one
      contraindication (n=12). Overall, we observed no differences between the
      reimbursement and non-reimbursement groups in the rate of SICH (7% versus 6%),
      dramatic improvement (36% versus 36%), good functional outcome (39% versus 37%),
      and in-hospital mortality (8% versus 6%) Conclusion: In stroke patients treated
      with intravenous thrombolysis according to the AHA/ASA guidelines, the outcomes
      were comparable between the reimbursement and non-reimbursement groups.

PMID- 28752509
TI  - The Association of Apolipoprotein E Allele 4 Polymorphism with the Recovery of
      Sleep Disturbance after Mild Traumatic Brain Injury.
AB  - PURPOSE: Mild traumatic brain injury (mTBI) is a major public health concern. The
      apolipoprotein E (APOE) gene contains three polymorphisms, and the APOE4
      polymorphism may affect several physiological states, such as the recovery from
      mTBI as well as sleep. This study aims to investigate the association between
      APOE4 with the recovery of sleep disturbance after mTBI. METHODS: From May 2012
      to Aug 2015, 189 mTBI patients completed baseline (1st week post-mTBI) and follow
      up (6th week post-mTBI) sleep assessments that involved using the Pittsburgh
      Sleep Quality Index (PSQI). APOE genotypes were determined by sequencing the
      products of polymerase chain reaction from genomic DNA. Statistical analyses were
      performed using the Wilcox signed-rank or chi-square test. RESULTS: Thirty-five
      (18.5%) participants were APOE4 carriers. At baseline, the demographic data and
      the severity of sleep disturbance were similar in both groups. APOE4 carriers
      demonstrated significant improvement in the overall PSQI score (8.34+/-3.9 at
      baseline and 7.43+/-3.99 at follow-up, p = 0.05) and scores of several PSQI
      subscales, including sleep disturbance, sleep latency, daytime dysfunction caused
      by sleepiness, and overall sleep quality, which was similar to APOE4 noncarriers.
      CONCLUSION: APOE4 is not associated with the recovery of sleep disturbance after
      mTBI.

PMID- 28752510
TI  - Comparison of LCModel and SAGE in Analysis of Brain Metabolite Concentrations-A
      study of Patients with Mild Cognitive Impairment.
AB  - PURPOSE: The purpose of this study was to compare brain metabolite concentration
      ratios determined by LCModel and Spectroscopy Analysis by General Electric (SAGE)
      quantitative methods to elucidate the advantages and disadvantages of each
      method. MATERIALS AND METHODS: A total of 10 healthy volunteers and 10 patients
      with mild cognitive impairment (MCI) were recruited in this study. A point
      resolved spectroscopy (PRESS) sequence was used to obtain the brain magnetic
      resonance spectroscopy (MRS) spectra of the volunteers and patients, as well as
      the General Electric (GE) MRS-HD-sphere phantom. The brain metabolite
      concentration ratios were estimated based on the peak area obtained from both
      LCModel and SAGE software. Three brain regions were sampled for each volunteer or
      patient, and 20 replicates were acquired at different times for the phantom
      analysis. RESULTS: The metabolite ratios of the GE phantom were estimated to be
      myo-inositol (mI)/creatine (Cr): 0.70 +/- 0.01, choline (Cho)/Cr: 0.37 +/- 0.00,
      N-acetylaspartate (NAA)/Cr: 1.26 +/- 0.02, and NAA/mI: 1.81 +/- 0.04 by LCModel,
      and mI/Cr: 0.88 +/- 0.15, Cho/Cr: 0.35 +/- 0.01, NAA/Cr: 1.33 +/- 0.03, and
      NAA/mI: 1.55 +/- 0.26 by SAGE. In the healthy volunteers and MCI patients, the
      ratios of mI/Cr and Cho/Cr estimated by LCModel were higher than those estimated
      by SAGE. In contrast, the ratio of NAA/Cr estimated by LCModel was lower than
      that estimated by SAGE. CONCLUSION: Both methods were acceptable in estimating
      brain metabolite concentration ratios. However, LCModel was marginally more
      accurate than SAGE because of its full automation, basis set, and user
      independency.

PMID- 28752511
TI  - Wernicke's Encephalopathy after Bariatric Surgery with Atypical Magnetic
      Resonance Imaging: A Case Report.
AB  - Wernicke's encephalopathy (WE) is a disease caused by thiamine deficiency related
      to alcoholism, hyperemesis, or thiamine malabsorption. The clinical
      manifestations of WE are mental change, ataxia, and ophthalmoplegia. The typical
      magnetic resonance imaging (MRI) findings of WE are symmetrical involvement of
      medial thalamus, periventricular region of the third ventricle, periaqueductal
      area, and mammillary body. The atypical MRI findings are more common in
      nonalcoholic WE. Since the increasing population of obesity and the preference of
      weight loss surgery, the risk of developing thiamine deficiencies associated with
      weight loss surgery has become a considerable etiology of WE. We herein reported
      a case reminds clinicians that WE can be a possible diagnosis in patient who
      developed acute altered mental status with atypical MRI lesion involving
      bilateral centrum semiovale and corona radiata after receiving bariatric surgery.

PMID- 28752512
TI  - Medical Treatment Guidelines for Preventive Treatment of Migraine.
AB  - The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the
      medications currently used for migraine prevention in Taiwan. We assessed the
      results of new published drug trials, information from medical database and
      referred to the latest guidelines published. After comprehensive discussion, we
      proposed Taiwanese consensus about the preventive treatment for migraine
      including recommendation levels, strength of evidences, and related prescription
      information regarding dosage and adverse effects. This guideline is updated from
      earlier version published in 2008. Migraine preventive medications currently
      available in Taiwan can be categorized into beta-blockers, antidepressants,
      calcium channel blockers, anticonvulsants, nonsteroid anti-inflammatory drugs,
      OnabotulinumtoxinA and miscellaneous medications. Propranolol has the best level
      of evidence and fewer side-effects, and is recommended as the first-line
      medication for episodic migraine prevention. Valproic acid, topiramate,
      flunarizine and amitriptyline are suggested as the second-line medications. The
      rest medications are used when the above medications fail. OnabotulinumtoxinA and
      topiramate are recommended for chronic migraine prevention. Those other
      medications used for episodic migraine could also be used as a second-line
      option. It is not recommended to use migraine preventive medication during
      pregnancy or lactation. For those women with menstrual migraine, nonsteroid anti
      inflammatory drugs and triptans can be used for prevention during the menstrual
      period. The levels of evidences for migraine preventive medications in
      children/adolescents and elderly are low. The preventive medications should
      follow the "start low and go slow" doctrine to reach an effective dosage. This
      can prevent adverse events and improve tolerance. The efficacy of preventive
      medications cannot be evaluated until 3 to 4 weeks after treatment. If the
      improvement of migraine maintains for 6 months, physicians can gradually taper
      the medications. Physicians should notify the patients not to overuse acute
      medications during migraine prevention treatment.

PMID- 28752513
TI  - Malnutrition-related early childhood exposures and enamel defects in the
      permanent dentition: A longitudinal study from the Bolivian Amazon.
AB  - OBJECTIVES: We investigated the relationship between early childhood malnutrition
      related measures and subsequent enamel defects in the permanent dentition.
      MATERIALS AND METHODS: This cohort study included 349 Amerindian adolescents (10
      17 years, 52% male) from the Bolivian Amazon. Exposures included: stunted growth
      (height-for-age z-scores), underweight (weight-for-age z-scores), anemia
      (hemoglobin), acute inflammation (C-reactive protein) and parasitic infection
      (hookworm). We measured the occurrence (no/yes) and extent (<1/3, 1/3-2/3, >2/3)
      of enamel defects. We estimated associations between childhood exposures and
      enamel defect measures using log-binomial and multinomial logistic regression.
      RESULTS: The prevalence of an enamel defect characterized by an orange peel
      texture on a large central depression on the labial surface of the central
      maxillary incisors was 92.3%. During childhood (1-4 years), participants had a
      high prevalence of stunted growth (75.2%), anemia (56.9%), acute inflammation
      (39.1%), and hookworm infection (49.6%). We observed associations between
      childhood height-for-age (OR = 0.65; P = 0.028 for >2/3 extent vs. no EH) and
      gastrointestinal hookworm infection (OR = 3.43; P = 0.035 for >2/3 extent vs. no
      defects or <1/3 extent) with enamel defects. DISCUSSION: The study describes a
      possibly novel form of enamel hypoplasia and provides evidence for associations
      of malnutrition-related measures in early childhood, including stunted growth and
      parasitic helminth infection, with the observed enamel defects.

PMID- 28752514
TI  - The impact of multifocal perineural invasion on biochemical recurrence and timing
      of adjuvant androgen-deprivation therapy in high-risk prostate cancer following
      radical prostatectomy.
AB  - BACKGROUND: Perineural invasion (PNI) is a distinct pathologic entity and a
      recognized source of tumor spread. However, the role of PNI in high-risk prostate
      cancer (PCa) has not been explored. The aims of the study were to investigate the
      impact of PNI on biochemical recurrence (BCR) and optimal timing of adjuvant
      androgen-deprivation therapy (ADT) after radical prostatectomy (RP). METHODS: A
      total of 265 prostatectomies, median follow-up 45 months, were assessed for the
      presence and intensity of PNI (unifocal and multifocal) in RP specimens. Kaplan
      Meier curves were used to estimate BCR probabilities. Cox proportional hazard
      models were used to address predictors of BCR. Harrell's C-index was conducted to
      further validate prognostic value of multi-PNI. RESULTS: A total of 123 patients
      (46.4%) were PNI positive, among which, 91 (74%) and 32 (26%) had unifocal PNI
      (uni-PNI) and multifocal PNI (multi-PNI), respectively. The presence of multi-PNI
      was strongly associated with increasing incidence of BCR (HR = 3.87, 95%CI: 1.66
      9.01, P = 0.002). Patients with uni-PNI had a similar BCR rate to those without
      PNI after adjuvant ADT. For men with multi-PNI, immediate ADT was superior to
      delayed ADT in decreasing biochemical failure. CONCLUSIONS: Our findings suggest
      that detection of multi-PNI in high-risk RP specimens could be a prognosticator
      for early biochemical relapse post-surgery. Initiation of adjuvant therapy may be
      appropriate in patients with multi-PNI as soon as possible after surgery.

PMID- 28752515
TI  - An interesting and unusual coronary artery anomaly.
AB  - Cardiac CT angiography utilized in the emergency room for triage of low-to
      intermediate risk chest pain on occasion identifies unexpected abnormalities. In
      this case, multiple coronary anomalies existed in the same patient. Images and
      clinical decision making are discussed in this presentation. Coronary anomalies
      are being recognized with increased frequency due to increasing use of this
      modality in the evaluation of chest pain. The clinical implications of these
      findings are not always clear.

PMID- 28752516
TI  - CYCLING DOF FACTOR 1 represses transcription through the TOPLESS co-repressor to
      control photoperiodic flowering in Arabidopsis.
AB  - CYCLING DOF FACTOR 1 (CDF1) and its homologs play an important role in the floral
      transition by repressing the expression of floral activator genes such as
      CONSTANS (CO) and FLOWERING LOCUS T (FT) in Arabidopsis. The day-length-specific
      removal of CDF1-dependent repression is a critical mechanism in photoperiodic
      flowering. However, the mechanism by which CDF1 represses CO and FT transcription
      remained elusive. Here we demonstrate that Arabidopsis CDF proteins contain non
      EAR motif-like conserved domains required for interaction with the TOPLESS (TPL)
      co-repressor protein. This TPL interaction confers a repressive function on CDF1,
      as mutations of the N-terminal TPL binding domain largely impair the ability of
      CDF1 protein to repress its targets. TPL proteins are present on specific regions
      of the CO and FT promoters where CDF1 binds during the morning. In addition, TPL
      binding increases when CDF1 expression is elevated, suggesting that TPL is
      recruited to these promoters in a time-dependent fashion by CDFs. Moreover,
      reduction of TPL activity induced by expressing a dominant negative version of
      TPL (tpl-1) in phloem companion cells results in early flowering and a decreased
      sensitivity to photoperiod in a manner similar to a cdf loss-of-function mutant.
      Our results indicate that the mechanism of CDF1 repression is through the
      formation of a CDF-TPL transcriptional complex, which reduces the expression
      levels of CO and FT during the morning for seasonal flowering.

PMID- 28752517
TI  - Nitrate reductases in Hydrogenobacter thermophilus with evolutionarily ancient
      features: distinctive localization and electron transfer.
AB  - Dissimilatory nitrate reductase (NAR) and assimilatory nitrate reductase (NAS)
      serve as key enzymes for nitrogen catabolism and anabolism in many organisms. We
      purified NAR and NAS from H. thermophilus, a hydrogen-oxidizing
      chemolithoautotroph belonging to the phylogenetically deepest branch in the
      Bacteria domain. Physiological contribution of these enzymes to nitrate
      respiration and assimilation was clarified by transcriptomic analysis and gene
      disruption experiments. These enzymes showed several features unreported in
      bacteria, such as the periplasmic orientation of NAR anchored with a putative
      transmembrane subunit and the specific electron transfer from a [4Fe-4S]-type
      ferredoxin to NAS. While some of their enzymatic properties are shared with NARs
      from archaea and with NASs from phototrophs, phylogenetic analysis indicated that
      H. thermophilus NAR and NAS have deep evolutionary origins that cannot be
      explained by a recent horizontal gene transfer event from archaea and
      phototrophs. These findings revealed the diversity of NAR and NAS in
      nonphotosynthetic bacteria, and they also implied that the outward orientation of
      NAR and the ferredoxin-dependent electron transfer of NAS are evolutionarily
      ancient features preserved in H. thermophilus.

PMID- 28752519
TI  - Nurses' use of mobile instant messaging applications: A uses and gratifications
      perspective.
AB  - AIM: To explore how and why mobile instant messaging applications are used by
      Filipino nurses as part of their work. METHODS: Guided by the uses and
      gratifications theory, in-depth interviews with 20 staff nurses working in 9
      hospitals (ie, 4 private and 5 public hospitals) in the Philippines were
      conducted in July 2015. Interview data were analysed through a phenomenological
      perspective to thematic analysis. RESULTS: Results show that mobile instant
      messaging applications such as Facebook Messenger and Viber were mostly used by
      staff nurses and these were accessed using their own smartphones. Thematic
      analysis indicates that they were used to meet staff nurses' need for information
      exchange, socialization, and catharsis. Moreover, user interactions vary
      depending on members within a chat group. For instance, communication via mobile
      instant messaging applications are much formal when superiors are included in a
      chat group. CONCLUSION: In general, the results show that mobile instant
      messaging applications are routinely used by Filipino staff nurses not only for
      clinical purposes (ie, information exchange) but also for non-clinical purposes
      (ie, socialization and catharsis). This paper ends with several practical and
      theoretical implications including future research directions.

PMID- 28752518
TI  - The color of cancer: Margin guidance for oral cancer resection using elastic
      scattering spectroscopy.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the usefulness of elastic scattering
      spectroscopy (ESS) as a diagnostic adjunct to frozen section analysis in patients
      with diagnosed squamous cell carcinoma of the oral cavity. STUDY DESIGN:
      Prospective analytic study. METHODS: Subjects for this single institution,
      institutional review board-approved study were recruited from among patients
      undergoing surgical resection for squamous cell cancer of the oral cavity. A
      portable ESS device with a contact fiberoptic probe was used to obtain spectral
      signals. Four to 10 spectral readings were obtained on each subject from various
      sites including gross tumor and normal-appearing mucosa in the surgical margin.
      Each reading was correlated with the histopathologic findings of biopsies taken
      from the exact location of the spectral readings. A diagnostic algorithm based on
      multidimensional pattern recognition/machine learning was developed. Sensitivity
      and specificity, error rate, and area under the curve were used as performance
      metrics for tests involving classification between disease and nondisease
      classes. RESULTS: Thirty-four (34) subjects were enrolled in the study. One
      hundred seventy-six spectral data point/biopsy specimen pairs were available for
      analysis. ESS distinguished normal from abnormal tissue, with a sensitivity
      ranging from 84% to 100% and specificity ranging from 71% to 89%, depending on
      how the cutoff between normal and abnormal tissue was defined (i.e., mild,
      moderate, or severe dysplasia). There were statistically significant differences
      in malignancy scores between histologically normal tissue and invasive cancer and
      between noninflamed tissue and inflamed tissue. CONCLUSIONS: This is the first
      study to evaluate the effectiveness of ESS in guiding mucosal resection margins
      in oral cavity cancer. ESS provides fast, real-time assessment of tissue without
      the need for pathology expertise. ESS appears to be effective in distinguishing
      between normal mucosa and invasive cancer and between "normal" tissue
      (histologically normal and mild dysplasia) and "abnormal" tissue (severe
      dysplasia and carcinoma in situ) that might require further margin resection.
      Further studies, however, are needed with a larger sample size to validate these
      findings and to determine the effectiveness of ESS in distinguishing visibly and
      histologically normal tissue from visibly normal but histologically abnormal
      tissue. LEVEL OF EVIDENCE: NA Laryngoscope, 127:S1-S9, 2017.

PMID- 28752520
TI  - Abstracts from the International Surgical Congress of the Association of Surgeons
      of Great Britain and Ireland, Glasgow, 2017.

PMID- 28752521
TI  - Effect of catheter size and injection rate of contrast agent on enhancement and
      image quality for triple-phase helical computed tomography of the liver in small
      dogs.
AB  - Rapid contrast injection is recommended for triple-phase helical computed
      tomography (CT) of the liver. However, a large-gauge catheter is needed for
      faster contrast injection and this is not practical for small breed dogs or cats.
      The purpose of this crossover group study was to evaluate applicability of a
      lower injection rate with a small-gauge (G) catheter for triple-phase hepatic CT
      in small dogs. Triple-phase CT images were acquired for six beagle dogs using
      three protocols: an injection rate of 1.5 ml/s with a 24 G catheter, 3.0 ml/s
      with a 22 G catheter, and 4.5 ml/s with a 20 G catheter. Enhancement of the
      aorta, portal vein, and hepatic parenchyma was measured in each phase (arterial,
      portal, and delayed) and image quality was scored subjectively by two observers.
      Injection duration, time to scan delay, and time to peak enhancement were also
      recorded. Contrast injection duration decreased with a higher injection rate (n =
      6, P <= 0.01), but time to peak enhancement and time to scan delay were not
      significantly affected by injection rates and catheter sizes. Contrast injection
      rate did not significantly affect aortic, portal, and hepatic enhancement. In
      addition, separation between each phase and quality of images was subjectively
      scored as good regardless of injection rate. Findings from the current study
      supported using an injection rate of 1.5 ml/s with a catheter size of 24 G for
      triple-phase hepatic CT in small dogs (weight < 12 kg).

PMID- 28752522
TI  - Pentoxifylline increases the level of nitric oxide produced by human spermatozoa.
AB  - Pentoxifylline (PF) is a xanthine derivative drug primarily used to treat
      peripheral vascular disorders. It is currently used in assisted reproductive
      technologies to enhance human sperm motility. However, the mechanism by which
      this enhancement occurs is not fully understood. Given that nitric oxide has been
      identified as a trigger to sperm motion, we asked whether nitric oxide modulates
      the stimulatory effect of PF on sperm motility. A total of 41 semen samples from
      infertile males were studied. Nitric oxide production in the presence of 5 mm PF
      was tested using different bio-analytical methods (spectrophotometry, fluorometry
      and fluorescence microscopy). The spectrophotometric determination showed higher
      levels of nitrite, an indirect measure for nitric oxide, in sperm samples
      supplemented with PF compared to controls. The fluorometric experiment showed
      higher 4, 5-diaminofluorescein triazole, a product from the reaction between
      nitric oxide and 4, 5-diaminofluorescein diacetate, after adding PF to
      spermatozoa. The fluorescence microscopy images of the spermatozoa supplemented
      with PF showed higher green fluorescence, indicating higher 4, 5
      diaminofluorescein triazole levels, compared to controls. It is concluded that PF
      enhances nitric oxide production in human spermatozoa, which explains, at least
      in part, the mechanism by which PF stimulates human sperm motility.

PMID- 28752523
TI  - Dermoscopy of lymphangioma circumscriptum: A morphological study of 45 cases.
AB  - BACKGROUND/OBJECTIVES: The dermoscopy of lymphangioma circumscriptum, also known
      as superficial lymphatic malformation, remains to be clarified. METHODS: Digital
      dermoscopic images of 45 histopathologically confirmed cases of lymphangioma
      circumscriptum collected from nine hospitals in Spain, Italy and Turkey were
      evaluated for the presence of dermoscopic structures and patterns. RESULTS: Our
      study shows that the most common structure found in lymphangioma circumscriptum
      was the presence of lacunae (89% of cases). The latter were red or dark-coloured
      in 18 cases (45%), yellowish or whitish in 14 cases (35%) and multicoloured in
      eight cases (20%). The second most common dermoscopic structure was the presence
      of vascular structures, which were found in 82% of cases, followed by white lines
      (47%), the hypopyon sign or two-tone lacunae (42%) and scales (7%). CONCLUSIONS:
      Dermoscopy is useful in improving the diagnosis of lymphangioma circumscriptum
      with characteristic structures and patterns and could assist in elucidating the
      presence of blood in lymphatic channels.

PMID- 28752524
TI  - Serial combination of non-invasive tools improves the diagnostic accuracy of
      severe liver fibrosis in patients with NAFLD.
AB  - BACKGROUND: The accuracy of available non-invasive tools for staging severe
      fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still
      limited. AIM: To assess the diagnostic performance of paired or serial
      combination of non-invasive tools in NAFLD patients. METHODS: We analysed data
      from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI,
      AST/ALT, BARD, FIB-4, and NAFLD Fibrosis Score (NFS) scores were calculated
      according to published algorithms. Liver stiffness measurement (LSM) was
      performed by FibroScan. RESULTS: LSM, NFS and FIB-4 were the best non-invasive
      tools for staging F3-F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively),
      with LSM having the highest sensitivity (90%), and the highest NPV (94%), and NFS
      and FIB-4 the highest specificity (97% and 93%, respectively), and the highest
      PPV (73% and 79%, respectively). The paired combination of LSM or NFS with FIB-4
      strongly reduced the likelihood of wrongly classified patients (ranging from 2.7%
      to 2.6%), at the price of a high uncertainty area (ranging from 54.1% to 58.2%),
      and of a low overall accuracy (ranging from 43% to 39.1%). The serial combination
      with the second test used in patients in the grey area of the first test and in
      those with high LSM values (>9.6 KPa) or low NFS or FIB-4 values (<-1.455 and
      <1.30, respectively) overall increased the diagnostic performance generating an
      accuracy ranging from 69.8% to 70.1%, an uncertainty area ranging from 18.9% to
      20.4% and a rate of wrong classification ranging from 9.2% to 11.3%. CONCLUSION:
      The serial combination of LSM with FIB-4/NFS has a good diagnostic accuracy for
      the non-invasive diagnosis of severe fibrosis in NAFLD.

PMID- 28752525
TI  - Differences in free-living and particle-associated bacterial communities and
      their spatial variation in Kongsfjorden, Arctic.
AB  - High throughput V3-16S rRNA amplicon sequencing data was used for evaluating
      differences between free-living (FL, <1.2-0.2 MUm) and particle-associated (PA,
      >1.2 MUm) bacterial communities, and their spatial variation between inner fjord
      (IF) and outer fjord (OF) of Kongsfjorden. A total of 4,454,142 high quality
      sequences obtained clustered into 32,058 OTUs. A majority of these sequences were
      affiliated with Proteobacteria (59.8%), followed by Bacteroidetes (29.02%),
      Firmicutes (5.9%), Actinobacteria (2.84%), Cyanobacteria (1.04%), and others
      (1.4%). The highest bacterial diversity was recorded in the inner fjord free
      living (IF_FL) fraction whilst the lowest was observed in the outer fjord free
      living (OF_FL) fraction. There was a clear spatial variation among FL bacterial
      communities, while PA communities remained similar at both sampling locations.
      The free-living bacterial community differs from particle-associated community
      and had relatively higher abundance (>4-fold) of Alteromonas and
      Pseudoalteromonas, while PA community was relatively more enriched with
      Balneatrix, Ulvibacter, Formosa, Candidatus Planktomarina, Sulfitobacter,
      Loktanella, members of SAR116, and Acidimicrobiales. In addition, two major
      bacterial taxa, Polaribacter and SAR11, co-occurred in both FL and PA fractions
      with varied proportions in IF and OF. These results suggest co-occurrence of PA
      specialist as well as generalist bacterial groups in Kongsfjorden. Further, high
      bacterial diversity in the IF_FL fraction indicates possible role of glacial
      inputs in modulating diversity of free-living bacterial community in
      Kongsfjorden.

PMID- 28752526
TI  - Dynamic properties of imidazolium orthoborate ionic liquids mixed with
      polyethylene glycol studied by NMR diffusometry and impedance spectroscopy.
AB  - We used 1 H pulsed field gradient nuclear magnetic resonance to study the self
      diffusion of polyethylene glycol (PEG) with average molecular mass of 200 and
      ions in mixtures of PEG with imidazolium bis(mandelato)borate (BMB) and
      imidazolium bis(oxalato)borate ionic liquids (ILs). The IL was mixed with PEG in
      the concentration range of 0-100 wt%. Within the temperature range of 295 to 353
      K, the diffusion coefficient of BMB is slower than that of the imidazolium
      cation. The diffusion coefficients of PEG, as well as the imidazolium cation and
      BMB anions, differ under all experimental conditions tested. This demonstrates
      that the IL in the mixture is present in at least a partially dissociated state.
      Generally, increasing the concentration of PEG leads to an increase in the
      diffusion coefficients of PEG and both the ions and decreases their activation
      energy for diffusion. Nuclear magnetic resonance chemical shift alteration
      analysis showed that the presence of PEG changes the chemical shifts of both ions
      but in different directions. Impedance spectroscopy was used to measure the ionic
      conductivity of the ILs mixed with PEG. Copyright (c) 2017 John Wiley & Sons,
      Ltd.

PMID- 28752527
TI  - Interleukin-15 in obesity and metabolic dysfunction: current understanding and
      future perspectives.
AB  - Obesity rises rapidly and is a major health concern for modern people.
      Importantly, it is a major risk factor in the development of numerous chronic
      diseases such as type 2 diabetes mellitus (T2DM). Recently, interleukin (IL)-15
      has attracted considerable attention as a potential regulator for the prevention
      and/or treatment of obesity and T2DM. The beneficial effects include increased
      loss of fat mass and body weight, improved lipid and glucose metabolism, reduced
      white adipose tissue inflammation, enhanced mitochondrial function, alterations
      in the composition of muscle fibres and gut bacterial and attenuated endoplasmic
      reticulum stress. Although these beneficial effects are somewhat controversial,
      IL-15, exogenously delivered or endogenously produced, may be a promising target
      in the prevention and treatment of obesity and T2DM.

PMID- 28752528
TI  - Folic acid modulates cancer-associated micro RNAs and inflammatory mediators in
      neoplastic and non-neoplastic colonic cells in a different way.
AB  - SCOPE: Scientific evidence suggests that folic acid (FA) supplementation protects
      the healthy colonic mucosa from neoplastic transformation but may promote the
      progression of precancerous lesions. The underlying molecular mechanisms are not
      fully understood. Therefore, we explored, if high physiological FA doses provoke
      changes in (i) promoter-specific DNA methylation (ii) expression of cancer
      associated micro RNAs (miRNAs) and (iii) inflammatory mediators in human
      neoplastic and non-neoplastic colonic cell lines. METHODS AND RESULTS: The
      malignant and the non-malignant colonic cell lines HT29 and HCEC were adapted to
      different near-physiological FA concentrations. Using DNA methylation and pathway
      specific PCR arrays, high-physiological FA concentrations revealed no relevant
      impact on promoter methylation but a number of differences between the cell lines
      in the expression of miRNAs and inflammatory mediators. In the HCEC cell line pro
      inflammatory genes were repressed and the miRNA expression remained nearly
      unaffected. In contrast, in the HT29 cell line tumour-suppressive miRNAs were
      predominantly down-regulated and the expression of genes involved in chemotaxis
      and immunity were modulated. CONCLUSION: The different effects of high
      physiological FA concentrations in malignant and non-malignant colonic cell lines
      regarding cancer-associated miRNAs and inflammatory mediators may contribute to
      the different effects of FA supplementation on colonic carcinogenesis.

PMID- 28752529
TI  - Predicting variations to missed nursing care: A three-nation comparison.
AB  - AIMS: To measure and model Australian, Cypriot and Italian nurses' beliefs about
      what care is missed and how frequently it occurs within their settings.
      BACKGROUND: This study expands on previous MISSCARE research but now applies and
      predicts missed care within three countries. METHODS: Multivariate analysis was
      performed to estimate 1,896 nurses' consensus scores about missed care activities
      based on Alfaro-Lefevre's conceptual framework of care priorities. RESULTS: Five
      latent variables have direct predictor effects on missed care frequencies.
      Another four variables including the nurses' age, highest qualifications,
      absenteeism rate and workplace type, contributed to explaining the overall
      variance of missed care scores. The nurses' gender had no influence on missed
      care. CONCLUSION: Cross country comparisons of missed nursing care allow for a
      more refined identification of strategies for remediation for both managers and
      clinicians. IMPLICATIONS FOR NURSING MANAGEMENT: Reliable consensus estimates
      about the types and frequencies of missed care can be scaled with variables
      identified to predict missed care across three different countries. Comparative
      international studies build on the foundations for understanding missed care in
      terms of nursing practices, policies and related social policies.

PMID- 28752530
TI  - HMGA2 regulates lung cancer proliferation and metastasis.
AB  - BACKGROUND: This study aimed to explore the effects of HMGA2 on cell
      proliferation and metastases in lung cancer and its underlying mechanism.
      METHODS: HMGA2 expression in lung cancer tissues and its association with overall
      survival were analyzed based on data from a public database. The roles of HMGA2
      were validated via loss-of-function and gain-of-function experiments in vitro.
      HMGA2 regulation by microRNA-195 (miR-195) was validated by real time-PCR,
      Western blotting, and luciferase reporter assays. RESULTS: HMGA2 was upregulated
      and associated with reduced overall survival in patients with lung
      adenocarcinoma. HMGA2 knockdown suppressed the proliferation and motility of
      H1299 cells, while HMGA2 ectopic expression in A549 cells increased cell
      proliferation and migration. HMGA2 affected cell apoptosis through caspase 3/9
      and Bcl-2, and regulated epithelial-to-mesenchymal transition by targeting Twist
      1. Moreover, miR-195 was found to directly target the 3' untranslated region of
      HMGA2 messenger RNA and suppress its expression in lung cancer. CONCLUSION: This
      study demonstrated that HMGA2, regulated by miR-195, played important roles in
      proliferation, metastases, and epithelial-to-mesenchymal transition in lung
      cancer. HMGA2 might serve as a biomarker and potential therapeutic target for
      lung cancer treatment.

PMID- 28752531
TI  - Cardiac sarcoidosis diagnosed by multimodality imaging.
AB  - A 66-year-old woman presented with frequent premature ventricular contractions
      (PVC) and akinesis of the basal septum on echocardiography. Coronary angiography
      was normal. Cardiac magnetic resonance showed mid-wall enhancement. Positron
      emission tomography showed a perfusion defect at the same location using 13N
      ammonia, but increased 18-fluorodeoxyglucose uptake. These findings supported the
      diagnosis of cardiac sarcoidosis. High-dose steroids initially reduced frequency
      of PVCs but had to be withdrawn due to severe side effects. An ICD was implanted.
      Our case demonstrates the utility of multimodality imaging to diagnose and guide
      management of this entity.

PMID- 28752532
TI  - Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast Cancer
      Cells.
AB  - Several studies have documented the ability of flavonoids to sensitize cancer
      cells to chemotherapeutics and reverse multidrug resistance by inhibition of
      efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis
      activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin
      3-O-beta-d-rutinoside) was investigated as chemosensitizer towards two different
      human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as
      representative for triple-negative breast cancer and (ii) MCF-7 used as a well
      characterized model of HER2-negative breast cancer. To assess the
      cytocompatibility of rutin against non-cancer cells, primary human mammary
      fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20
      MUM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate.
      Rutin significantly (p < 0.05) increased the anticancer activity of both
      chemotherapeutics, at 24-48-72 h, and decreased the activity of the adenosine
      triphosphate-binding cassette transporters, namely, P-glycoprotein (P-gp) and
      breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 MUM
      and 50 MUM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively,
      significantly promoting cell apoptosis. Rutin, via non-selective inhibition of P
      gp and BCRP pumps, efficiently reverses multidrug resistance and restores
      chemosensitivity to cyclophosphamide and cyclophosphamide of human
      chemoresistant, triple-negative breast cancer cells, successfully arresting cell
      cycle progression. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28752533
TI  - An improved null model for assessing the net effects of multiple stressors on
      communities.
AB  - Ecological stressors (i.e., environmental factors outside their normal range of
      variation) can mediate each other through their interactions, leading to
      unexpected combined effects on communities. Determining whether the net effect of
      stressors is ecologically surprising requires comparing their cumulative impact
      to a null model that represents the linear combination of their individual
      effects (i.e., an additive expectation). However, we show that standard additive
      and multiplicative null models that base their predictions on the effects of
      single stressors on community properties (e.g., species richness or biomass) do
      not provide this linear expectation, leading to incorrect interpretations of
      antagonistic and synergistic responses by communities. We present an alternative,
      the compositional null model, which instead bases its predictions on the effects
      of stressors on individual species, and then aggregates them to the community
      level. Simulations demonstrate the improved ability of the compositional null
      model to accurately provide a linear expectation of the net effect of stressors.
      We simulate the response of communities to paired stressors that affect species
      in a purely additive fashion and compare the relative abilities of the
      compositional null model and two standard community property null models
      (additive and multiplicative) to predict these linear changes in species richness
      and community biomass across different combinations (both positive, negative, or
      opposite) and intensities of stressors. The compositional model predicts the
      linear effects of multiple stressors under almost all scenarios, allowing for
      proper classification of net effects, whereas the standard null models do not.
      Our findings suggest that current estimates of the prevalence of ecological
      surprises on communities based on community property null models are unreliable,
      and should be improved by integrating the responses of individual species to the
      community level as does our compositional null model.

PMID- 28752534
TI  - Structural basis for substrate selection by the translocation and assembly module
      of the beta-barrel assembly machinery.
AB  - The assembly of proteins into bacterial outer membranes is a key cellular process
      that we are only beginning to understand, mediated by the beta-barrel assembly
      machinery (BAM). Two crucial elements of that machinery are the core BAM complex
      and the translocation and assembly module (TAM), with each containing a member of
      the Omp85 superfamily of proteins: BamA in the BAM complex, TamA in the TAM.
      Here, we used the substrate protein FimD as a model to assess the selectivity of
      substrate interactions for the TAM relative to those of the BAM complex. A
      peptide scan revealed that TamA and BamA bind the beta-strands of FimD, and do so
      selectively. Chemical cross-linking and molecular dynamics are consistent with
      this interaction taking place between the first and last strand of the TamA
      barrel domain, providing the first experimental evidence of a lateral gate in
      TamA: a structural element implicated in membrane protein assembly. We suggest
      that the lateral gates in TamA and BamA provide different environments for
      substrates to engage, with the differences observed here beginning to address how
      the TAM can be more effective than the BAM complex in the folding of some
      substrate proteins.

PMID- 28752536
TI  - Multimodality imaging of primary ureteral hemangiosarcoma with thoracic
      metastasis in an adult dog.
AB  - A 12-year-old spayed female standard Poodle was presented for investigation of
      severe hematuria. Abdominal ultrasound and thoracic and abdominal computed
      tomography identified severe hydronephrosis due to an obstructive ureteral mass
      with no evidence of metastasis. Histological examination after nephrectomy and
      ureterectomy confirmed an obstructive ureteral hemangiosarcoma. Forty days after
      surgery, the dog was presented with severe dyspnea. Survey radiographs of the
      thorax revealed a severe diffuse nodular interstitial pattern. Postmortem
      histological examination revealed pulmonary metastasis of hemangiosarcoma.

PMID- 28752535
TI  - Nurse prescribing in Spain: The law and the curriculum.
AB  - In this cross-sectional study, we explored course content related to pharmacology
      and/or healthcare products and supplies in all nursing degree programs in Spain.
      Changes in nurse-prescribing legislation in Spain require that nurses take a
      certification course before prescribing over-the-counter products and
      medications. Using a cross-sectional descriptive study, between July and
      September 2014, the degree programs of all centers that offer a degree in nursing
      in Spain were examined, selecting those with course information available online.
      All centers offered at least one pharmacology course. One-third of the required
      courses had content related to pharmacology and healthcare products/supplies. The
      analysis showed that the course content and training received during the current
      nursing degree program provides the knowledge and skills needed to prescribe
      healthcare products/supplies and medications that do not now require a doctor's
      prescription, without the need for additional training and certification. It is
      essential that government regulation of nursing education be aligned with nursing
      competencies, curriculum standards, clinical practice, and evidence-based
      research to provide the maximum level of confidence for nursing professionals and
      their patients.

PMID- 28752537
TI  - Utility of bronchoscopy in the definitive diagnosis of patients with
      haematological malignancies presenting with radiological abnormalities.
AB  - INTRODUCTION: Patients with haematological malignancies usually have a plethora
      of respiratory complications. Bronchoscopy is one of the most important
      procedures used to diagnose respiratory complications. Despite enormous benefit,
      patients should be carefully selected for bronchoscopy as the process is
      invasive; however, there are only few reports evaluating the contributing factors
      of bronchoscopy that result in the definitive diagnosis of respiratory
      complications in these patients. OBJECTIVE: This study aimed to elucidate and
      identify the contributing factors of bronchoscopy for definitive diagnosis in
      patients with haematological malignancies. METHODS: We retrospectively analysed
      275 patients with haematological malignancies who later showed respiratory
      complications, requiring consultation with pulmonologists. We found that 62
      patients underwent bronchoscopy. Our data analysis focused on this particular
      subset of patients to identify the factors crucial for definitive diagnosis via
      bronchoscopy. RESULTS: Bronchoscopy provided definitive diagnosis for 25 patients
      (diagnostic yield = 40.3%). We determined that nodular shadow was associated with
      high diagnostic yields by multivariate logistic regression [odds ratio (OR): 6.6
      (2.1-23)]. Furthermore, in several bronchoscopic procedures, biopsy also
      contributed to definitive diagnosis of patients with nodular shadow [OR: 17 (1.5
      180)]. Life-threatening complications were not observed due to bronchoscopy in
      our study. CONCLUSIONS: Our study demonstrated that patients with haematological
      malignancies who showed lung nodular shadows are more likely to be definitively
      diagnosed by bronchoscopy, whereas transbronchial biopsy may also be beneficial
      for these patients.

PMID- 28752538
TI  - Clinicopathologic features of lingual canine T-zone lymphoma.
AB  - Canine T-zone lymphoma (TZL) is a subtype of T-cell lymphoma characterized by
      unique histologic pattern and cytomorphology, immunophenotypic loss of CD45
      expression, and an indolent clinical behaviour. Dogs with TZL typically present
      with 1 or more enlarged lymph nodes and/or lymphocytosis. We describe a novel
      extranodal presentation of TZL involving the tongue. Twelve dogs with tongue
      masses were diagnosed with lingual TZL based on a variable combination of
      immunophenotyping via flow cytometry, cytology, histopathology,
      immunohistochemistry and/or PCR for antigen receptor rearrangement (PARR) assay.
      Eleven dogs exhibited concurrent lymphocytosis and/or lymph node enlargement.
      Three cases were initially diagnosed as plasma cell tumours based on histology
      alone, thereby revealing a potential diagnostic challenge. Seven dogs achieved
      clinical remission and 4 achieved stable disease following variable treatment,
      consistent with the indolent nature of typical TZL involving the lymph nodes and
      peripheral blood. In 1 case the TZL resulted in progressive disease and failure
      to respond to treatment. In this case, the TZL exhibited histologic features of a
      higher grade neoplasm. This case series highlights a unique presentation of TZL
      and identifies a new differential diagnosis for lingual neoplasia. In this study,
      we characterize the clinical presentation, diagnostic features and patient
      outcomes of 12 dogs with lingual TZL.

PMID- 28752539
TI  - Disparities in Treatment of Older Adults with Suicide Risk in the Emergency
      Department.
AB  - BACKGROUND/OBJECTIVE: We described characteristics and treatment received for
      older (>=60 years) vs younger (<60 years) adult emergency department (ED)
      patients with suicide risk. DESIGN: Retrospective chart review. SETTING: An ED
      with universal screening for suicide risk. PARTICIPANTS: Eligible charts included
      a random sample of adults (>=18 years) who screened positive for suicidal
      ideation (SI) in past 2 weeks and/or a suicide attempt (SA) within the past 6
      months. Visit dates were from May 2014 to September 2016. RESULTS: A total of 800
      charts were reviewed, with oversampling of older adults. Of the 200 older adults
      sampled, fewer older adults compared to younger adults (n = 600) had a chief
      complaint involving psychiatric behavior (53% vs 70%) or self-harm behavior (26%
      vs 36%). Although a higher number of older adults (93%) had documentation of
      current SI compared to younger adults (79%), fewer older adults (17%) reported SA
      in the past 2 weeks compared to younger adults (23%). Of those with a positive
      suicide screen who were discharged home, less than half of older adults received
      a mental health evaluation during their visit (42%, 95% CI 34-52) compared to 66%
      (95% CI 61-70) of younger adults who met the same criteria. Similarly, fewer
      older, than younger, adult patients with current SI/SA received referral
      resources (34%; 95% CI 26-43; vs 60%; 95% CI 55-65). CONCLUSIONS: Significantly
      fewer suicidal older adult patients who were discharged home received a mental
      health evaluation when compared to similar younger adults. These findings
      highlight an important area for improvement in the treatment of older adults at
      risk for suicide.

PMID- 28752540
TI  - The effects of traffic light labelling versus cartoon labelling on food and
      beverage purchases in a children's hospital setting.
AB  - This study's purpose was to examine changes in healthy and unhealthy items
      purchased following the implementation of traffic light and cartoon labelling in
      a small retail food venue (Cafe Bay) in a children's hospital in eastern North
      Carolina. Between October 2015 and March 2016, daily food and beverage sales from
      Cafe Bay were obtained during baseline, traffic light labelling, a washout
      period, cartoon labelling (on healthy foods only) and a final washout period.
      Pearson chi-squared tests and multiple linear regressions were used to examine
      effects of labelling strategies, controlling for the holidays. In unadjusted
      analyses, traffic light labelling was associated with significant decreases in
      purchases of unhealthy items purchased, while cartoon labelling was associated
      with increases in unhealthy items purchased. In adjusted linear regression
      analysis, traffic light labelling was associated with fewer unhealthy purchases
      and thus may have potential to decrease the amount of unhealthy items purchased
      in a children's hospital food retail venue.

PMID- 28752541
TI  - Functionalization of porous BCP scaffold by generating cell-derived extracellular
      matrix from rat bone marrow stem cells culture for bone tissue engineering.
AB  - The potential of decellularized cell-derived extracellular matrix (ECM) deposited
      on biphasic calcium phosphate (BCP) scaffold for bone tissue engineering was
      investigated. Rat derived bone marrow mesenchymal stem cells were cultured on
      porous BCP scaffolds for 3 weeks and decellularized with two different methods
      (freeze-thaw [F/T] or sodium dodecyl sulfate [SDS]). The decellularized ECM
      deposited scaffolds (dECM-BCP) were characterized through scanning electron
      microscopy, energy dispersive X-ray spectrometer, and confocal microscopy. The
      efficiency of decellularization was evaluated by quantifying remaining DNA,
      sulfated glycosaminoglycans, and collagens. Results revealed that F/T method was
      more effective procedure for removing cellular components of cultured cells
      (95.21% DNA reduction) than SDS treatment (92.49%). Although significant loss of
      collagen was observed after decellularization with both F/T (56.68%) and SDS
      (70.87%) methods, F/T treated sample showed higher retaining amount of sulfated
      glycosaminoglycans content (75.64%) than SDS (33.28%). In addition, we
      investigated the cell biocompatibility and osteogenic effect of dECM-BCP
      scaffolds using preosteoblasts (MC3T3-E1). Compared to bare BCP scaffolds, dECM
      BCP_F/T scaffolds showed improved cell attachment and proliferation based on
      immunofluorescence staining and water soluble tetrazolium salts assay (p < .001).
      Moreover, dECM-BCP scaffolds showed increased osteoblastic differentiation of
      newly seeded preosteoblasts by up-regulating three types of osteoblastic genes
      (osteopontin, alkaline phosphatase, and bone morphogenic protein-2). This study
      demonstrated that functionalization of BCP scaffold using cell-derived ECM could
      be useful for improving the bioactivity of materials and providing suitable
      microenvironment, especially for osteogenesis. Further study is needed to
      determine the potential of dECM-BCP scaffold for bone formation and regeneration
      in vivo.

PMID- 28752542
TI  - Steady, relentless progress towards effective, safe screening for early detection
      of cancer of the ovary.

PMID- 28752543
TI  - Exonal switch down-regulates the expression of CD5 on blasts of acute T cell
      leukaemia.
AB  - To date, CD5 expression and its role in acute T cell lymphoblastic leukaemia (T
      ALL) have not been studied closely. We observed a significant reduction in
      surface expression of CD5 (sCD5) on leukaemic T cells compared to autologous non
      leukaemic T cells. In this study, we have shown the molecular mechanism
      regulating the expression and function of CD5 on leukaemic T cells. A total of
      250 patients suffering from leukaemia and lymphoma were immunophenotyped. Final
      diagnosis was based on their clinical presentation, morphological data and flow
      cytometry-based immunophenotyping. Thirty-nine patients were found to be of ALL-T
      origin. Amplification of early region of E1A and E1B transcripts of CD5 was
      correlated with the levels of surface and intracellular expression of CD5
      protein. Functional studies were performed to show the effect of CD5 blocking on
      interleukin IL-2 production and survival of leukaemic and non-leukaemic cells.
      Lack of expression of sCD5 on T-ALL blasts was correlated closely with
      predominant transcription of exon E1B and significant loss of exon E1A of the CD5
      gene, which is associated with surface expression of CD5 on lymphocytes. High
      expression of E1B also correlates with increased expression of cytoplasmic CD5
      (cCD5) among leukaemic T cells. Interestingly, we observed a significant increase
      in the production of IL-2 by non-leukaemic T cells upon CD5 blocking, leading
      possibly to their increased survival at 48 h. Our study provides understanding of
      the regulation of CD5 expression on leukaemic T cells, and may help in
      understanding the molecular mechanism of CD5 down-regulation.

PMID- 28752544
TI  - Three cases of lymphocytic thrombophilic arteritis presenting with an annular
      eruption.
AB  - We describe three patients who presented with a striking erythematous non
      blanching annular eruption and features of lymphocytic thrombophilic arteritis
      (LTA), with a prominent lymphocytic vasculitis involving deep dermal vessels.
      Lymphocytic inflammation was also evident in the superficial vessels and one
      patient had small superficial ulcers over the ankle area resembling livedoid
      vasculopathy (LV). Multiple biopsies demonstrated a persistent absence of
      neutrophils in the infiltrate consistent with a lymphocytic process. In addition
      to highlighting the annular morphology as a novel presentation of LTA, these
      cases suggest a possible relationship between LV and LTA and support the notion
      that they are distinct from neutrophilic vasculitides such as cutaneous
      polyarteritis nodosa.

PMID- 28752545
TI  - Broadband-Emitting 2 D Hybrid Organic-Inorganic Perovskite Based on Cyclohexane
      bis(methylamonium) Cation.
AB  - A new broadband-emitting 2 D hybrid organic-inorganic perovskite (CyBMA)PbBr4
      based on highly flexible cis-1,3-bis(methylaminohydrobromide)cyclohexane
      (CyBMABr) core has been designed, synthesized, and investigated, highlighting the
      effects of stereoisomerism of the templating cation on the formation and
      properties of the resulting perovskite. The new 2 D material has high exciton
      binding energy of 340 meV and a broad emission spanning from 380 to 750 nm,
      incorporating a prominent excitonic band and a less intense broad peak at room
      temperature. Significant changes in the photoluminescence (PL) spectrum were
      observed at lower temperatures, showing remarkable enhancement in the intensity
      of the broadband at the cost of excitonic emission. Temperature-dependent PL
      mapping indicates the effective role of only a narrow band of excitonic
      absorption in the generation of the active channel for emission. Based on the
      evidences obtained from the photophysical investigations, we attributed the
      evolution of the broad B-band of (CyBMA)PbBr4 to excitonic self-trapped states.

PMID- 28752546
TI  - Mandatory waiting periods and biased abortion counseling in Central and Eastern
      Europe.
AB  - Several Central and Eastern European countries have recently enacted
      retrogressive laws and policies introducing new preconditions that women must
      fulfill before they can obtain legal abortion services. Mandatory waiting periods
      and biased counseling and information requirements are particularly common
      examples of these new prerequisites. The present article considers these
      requirements in light of international human rights standards and public health
      guidelines, and outlines the manner in which, by imposing regressive barriers on
      women's access to legal abortion services, these new laws and policies undermine
      women's health and well-being, fail to respect women's human rights, and
      reinforce harmful gender stereotypes and abortion stigma.

PMID- 28752547
TI  - Inflammation and insulin resistance: New targets encourage new thinking: Galectin
      3 and LTB4 are pro-inflammatory molecules that can be targeted to restore insulin
      sensitivity.
AB  - Galectin-3 and LTB4 are pro-inflammatory molecules recently shown to directly
      cause insulin resistance in mouse and human cells. They are highly expressed in
      the obese state, and can be targeted both genetically and pharmacologically to
      improve insulin sensitivity in vivo. This expands on previous research showing
      that targeting inflammatory cytokines can be insulin sensitizing in animal
      models. However, translating these potential therapies into the human setting
      remains challenging. Here we review this latest research, and discuss how
      balancing their pleiotropic functions, the action of the microbiome, and the
      ability to identify relevant patient populations are vital considerations for
      successful anti-inflammatory insulin sensitizing therapy.

PMID- 28752548
TI  - Insecticide resistance, associated mechanisms and fitness aspects in two
      Brazilian Stegomyia aegypti (= Aedes aegypti) populations.
AB  - In Brazil, insecticide resistance in Stegomyia aegypti (= Aedes aegypti)
      (Diptera: Culicidae) populations to pyrethroids and to the organophosphate (OP)
      temephos is disseminated. Currently, insect growth regulators (IGRs) and the OP
      malathion are employed against larvae and adults, respectively. Bioassays with
      mosquitoes from two northeast municipalities, Crato and Aracaju, revealed, in
      both populations, susceptibility to IGRs and malathion (RR95  <= 2.0), confirming
      the effectiveness of these compounds. By contrast, temephos and deltamethrin
      (pyrethroid) resistance levels were high (RR95  > 10), which is consistent with
      the use of intense chemical control. In Crato, RR95 values were > 50 for both
      compounds. Knock-down-resistant (kdr) mutants in the voltage-gated sodium
      channel, the pyrethroid target site, were found in 43 and 32%, respectively, of
      Aracaju and Crato mosquitoes. Biochemical assays revealed higher metabolic
      resistance activity (esterases, mixed function oxidases and glutathione-S
      transferases) at Aracaju. With respect to fitness aspects, mating effectiveness
      was equivalently impaired in both populations, but Aracaju mosquitoes showed more
      damaging effects in terms of longer larval development, decreased bloodmeal
      acceptance, reduced engorgement and lower numbers of eggs laid per female.
      Compared with mosquitoes in Crato, Aracaju mosquitoes exhibited lower OP and
      pyrethroid RR95 , increased activity of detoxifying enzymes and greater effect on
      fitness. The potential relationship between insecticide resistance mechanisms and
      mosquito viability is discussed.

PMID- 28752549
TI  - Choice predicts the feedback negativity.
AB  - Choosing the appropriate response given the circumstance is integral to all
      aspects of human behavior. One way of elucidating the mechanisms of choice is to
      relate behavior to neural correlates. Electrophysiological evidence implicates
      the ERP feedback-negativity (FN) and the P300 as promising neural correlates of
      reward processing, an integral component of learning. However, prior research has
      not adequately addressed how the development of a preference to select one option
      over another (choice preference) relates to the FN and the P300. We assessed
      whether variation in choice preference predicted the FN and P300 amplitude within
      subjects. We used a discrete-trials two-alternative choice procedure, where the
      reinforcer rate for each option was dependently scheduled by a concurrent
      variable interval. The reinforcer ratio for selecting each option was varied
      between sessions. Choice was quantified using both the generalized matching law
      sensitivity and the log odds of staying on the same versus switching to the other
      alternative (stay preference). The relationship between stay preference, FN, and
      P300 amplitudes was assessed using the innovative application of hierarchical
      Bayesian linear regression. The results demonstrate that stay preference was
      controlled by the reinforcer ratios and credibly predicted the FN amplitude but
      not P300 amplitude. The findings are consistent with the view that reinforcers
      may guide behavior by what they signal about future reinforcement, with the FN
      related to such a process.

PMID- 28752550
TI  - Four-dimensional echocardiography area strain combined with exercise stress
      echocardiography to evaluate left ventricular regional systolic function in
      patients with mild single vessel coronary artery stenosis.
AB  - BACKGROUND: The aim of this prospective study was to assess the diagnosis value
      of four-dimensional echocardiography area strain (AS) combined with exercise
      stress echocardiography to evaluate left ventricular regional systolic function
      in patients with mild single vessel coronary artery stenosis. METHODS: Based on
      treadmill exercise load status, two-dimensional conventional echocardiography and
      four-dimensional echocardiography area strain were performed on patients
      suspected coronary artery disease before coronary angiogram. Thirty patients
      (case group) with mild left anterior descending coronary artery stenosis
      (stenosis <50%) and thirty gender- and age-matched patients (control group)
      without coronary artery stenosis according to the coronary angiogram results were
      prospectively enrolled. RESULTS: All the patients had no left ventricular
      regional wall motion abnormality in two-dimensional echocardiography at rest and
      exercise stress. There was no significant difference in the 16 segmental systolic
      peak AS at rest between two groups. After exercise stress, the peak systolic
      ASrest-stress at mid anterior wall (-7.00%+/-10.90% vs 2.80%+/-23.69%) and mid
      anterolateral wall (-4.40%+/-18.81% vs 8.80%+/-19.16%) were decreased, while
      increased at basal inferolateral wall (14.00%+/-19.27% vs -5.60%+/-15.94%) in
      case group compared with control group (P<.05). CONCLUSIONS: In patients with
      mild single vessel coronary artery stenosis, the area strain was decreased at
      involved segments, while compensatory increased at noninvolved segments after
      exercise stress. Four-dimensional echocardiography area strain combined with
      exercise stress echocardiography could sensitively find left ventricular regional
      systolic function abnormality in patients with mild single vessel coronary artery
      stenosis, and locate stenosis coronary artery accordingly.

PMID- 28752551
TI  - Point-of-care instruments need to offer high levels of accuracy.

PMID- 28752552
TI  - The two-component response regulator Skn7 belongs to a network of transcription
      factors regulating morphogenesis in Candida albicans and independently limits
      morphogenesis-induced ROS accumulation.
AB  - Skn7 is a conserved fungal heat shock factor-type transcriptional regulator. It
      participates in maintaining cell wall integrity and regulates the
      osmotic/oxidative stress response (OSR) in S. cerevisiae, where it is part of a
      two-component signal transduction system. Here, we comprehensively address the
      function of Skn7 in the human fungal pathogen Candida albicans. We provide
      evidence reinforcing functional divergence, with loss of the cell wall/osmotic
      stress-protective roles and acquisition of the ability to regulate morphogenesis
      on solid medium. Mapping of the Skn7 transcriptional circuitry, through
      combination of genome-wide expression and location technologies, pointed to a
      dual regulatory role encompassing OSR and filamentous growth. Genetic interaction
      analyses revealed close functional interactions between Skn7 and master
      regulators of morphogenesis, including Efg1, Cph1 and Ume6. Intracellular
      biochemical assays revealed that Skn7 is crucial for limiting the accumulation of
      reactive oxygen species (ROS) in filament-inducing conditions on solid medium.
      Interestingly, functional domain mapping using site-directed mutagenesis allowed
      decoupling of Skn7 function in morphogenesis from protection against
      intracellular ROS. Our work identifies Skn7 as an integral part of the
      transcriptional circuitry controlling C. albicans filamentous growth and
      illuminates how C. albicans relies on an evolutionarily-conserved regulator to
      protect itself from intracellular ROS during morphological development.

PMID- 28752553
TI  - Physical activity, sedentary behaviour, and psychosocial well-being among young
      South Korean children.
AB  - OBJECTIVE: To examine associations between television (TV) viewing, reading,
      physical activity (PA), and psychosocial well-being among a representative sample
      of young South Korean children aged 0-5 years. METHODS: Findings are based on
      1,774 children who participated in the Korea Children and Youth Survey. All
      measures were questionnaire-derived. Psychosocial well-being included social,
      interactive, and emotional skills (alpha = .7-.9), and the top quartile denoted
      high psychosocial well-being. Multiple logistic regressions were performed to
      examine relationships after controlling for several confounders. RESULTS:
      Compared to children who participated in PA for <1 hr/week, those who
      participated in PA for 1- <3 hr/week were more likely to show high emotional
      skills (odds ratio [OR]: 1.40, 95% confidence interval [CI] [1.02, 1.93]), and
      those who participated >=3 hr/week were more likely to show high social (OR:
      2.01, 95% CI [1.45, 2.78]) and interactive skills (OR: 1.39, 95% CI [1.01,
      1.92]). During weekdays, children who read 1- <3 hr/day and >=3 hr/day, compared
      to <1 hr/day, were more likely to show high social (OR: 1.61, 95% CI [1.20, 2.16]
      and OR: 2.47, 95% CI [1.31, 4.67]) and emotional skills (OR: 1.57, 95% CI [1.16,
      2.13] and OR: 2.58, 95% CI [1.34, 4.98]). In addition, children who read 1- <3
      hr/day, compared to <1 hr/day, were more likely to show high interactive skills
      (OR: 1.44, 95% CI [1.08, 1.92]). Similar findings for reading on weekends were
      observed. TV viewing was not associated with social skills or interactive skills.
      TV viewing for 1- <3 hr/day, compared to <1 hr/day, was associated with increased
      odds of high emotional skills (OR: 1.71, 95% CI [1.28, 2.27] on weekdays; OR:
      1.90, 95% CI [1.39, 2.61] on weekends). CONCLUSION: PA and reading primarily
      showed favourable associations with psychosocial well-being, whereas TV viewing
      did not; thus, PA or reading may be a better option over TV viewing for optimal
      psychosocial well-being among young South Korean children. These findings should
      be confirmed with stronger study designs.

PMID- 28752554
TI  - A systematic review of the impact of mindfulness on the well-being of healthcare
      professionals.
AB  - OBJECTIVE: Among efforts to improve the well-being of healthcare professionals
      are initiatives based around mindfulness meditation. To understand the value of
      such initiatives, we conducted a systematic review of empirical studies
      pertaining to mindfulness in healthcare professionals. METHOD: Databases were
      reviewed from the start of records to January 2016. Eligibility criteria included
      empirical analyses of mindfulness and well-being outcomes acquired in relation to
      practice. 81 papers met the eligibility criteria, comprising a total of 3,805
      participants. Studies were principally examined for outcomes such as burnout,
      distress, anxiety, depression, and stress. RESULTS: Mindfulness was generally
      associated with positive outcomes in relation to most measures (although results
      were more equivocal with respect to some outcomes, most notably burnout).
      CONCLUSION: Overall, mindfulness does appear to improve the well-being of
      healthcare professionals. However, the quality of the studies was inconsistent,
      so further research is needed, particularly high-quality randomized controlled
      trials.

PMID- 28752556
TI  - 3D-multi-echo radial imaging of 23 Na (3D-MERINA) for time-efficient multi
      parameter tissue compartment mapping.
AB  - PURPOSE: This work demonstrates a 3D radial multi-echo acquisition scheme for
      time-efficient sodium (23 Na) MR-signal acquisition and analysis. Echo
      reconstructions were used to produce signal-to-noise ratio (SNR)-enhanced 23 Na
      images and parameter maps of the biexponential observed transverse relaxation
      time ( T2*) decay. METHODS: A custom-built sequence for radial multi-echo
      acquisition was proposed for acquisition of a series of 3D volumetric 23 Na
      images. Measurements acquired in a phantom and in vivo human brains were analyzed
      for SNR enhancement and multi-component T2* estimation. RESULTS: Rapid gradient
      refocused imaging acquired 38 echoes within a repetition time of 160 ms. Signal
      averaging of multi-echo time (TE) measurements showed an average brain tissue SNR
      enhancement of 34% compared to single-TE images across subjects. Phantom and in
      vivo measurements detected distinguishable signal decay characteristics for fluid
      and solid media. Mapping results were investigated in phantom and in vivo
      experiments for sequence timing optimization and signal decay analysis. The T2*
      mapping results were consistent with previously reported values and facilitated
      fluid-signal discrimination. CONCLUSION: The proposed method offers an efficient
      23 Na-imaging scheme that extends existing 23 Na-MRI sequences by acquiring
      signal decay information with no increase in time or specific absorption rate.
      The resultant SNR-enhanced 23 Na-images and estimated T2* signal decay
      characteristics offer great potential for detailed investigation of tissue
      compartment characterization and clinical application. Magn Reson Med 79:1950
      1961, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

PMID- 28752555
TI  - Relationships between Medication Adherence and Cardiovascular Disease Risk Factor
      Control in Elderly Patients with Diabetes.
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) Medicare Star
      program provides incentives to health plans when their patients with diabetes
      meet adherence targets to angiotensin-converting enzyme inhibitors/angiotensin II
      receptor blockers (ACEIs/ARBs) and statins. While a link between adherence and
      cardiovascular risk factor control is established, most studies included young
      patients with few comorbidities. Whether the Star adherence target is associated
      with reduced blood pressure or low-density lipoprotein cholesterol (LDL-C) in
      complex older patients is not well understood. OBJECTIVES: Determine correlates
      of adherence and examine the effect of meeting Star adherence targets on blood
      pressure and LDL-C in the Medicare-aged diabetes population. DESIGN AND SUBJECTS:
      Retrospective cohort study of 129,040 patients with diabetes aged 65 or older.
      MEASURES: Adherence estimated using proportion of days covered target >= 0.8;
      blood pressure < 140/90 mg Hg; LDL-C < 100 mg/dl. Modified Poisson regression
      used to assess relationships. RESULTS: Adherence differed little across elderly
      age groups. Compared to no comorbidity, high comorbidity (>= 4) was associated
      with lower ACEI/ARB (risk ratio [RR] 0.88 [95% confidence interval (CI) 0.87
      0.89]) or statin (RR 0.91 [0.90-0.92]) adherence. ACEI/ARB adherence was not
      associated with blood pressure < 140/90 mm Hg in patients >= 85 years (RR 1.01
      [0.96-1.07]) or with multiple comorbidities (e.g., 3: RR 1.04 [0.99-1.08]).
      Statin adherence and LDL-C < 100 mg/dl were associated in all elderly age groups
      (e.g., >= 85: RR 1.13 [1.09-1.16]) and comorbidity levels (e.g., >= 4: RR 1.13
      [1.12-1.15]). CONCLUSIONS: Adherence to ACEI/ARB is not linked with reduced blood
      pressure in patients with diabetes who are at least 85 years or with multiple
      comorbidities.

PMID- 28752557
TI  - Retort beef aroma that gives preferable properties to canned beef products and
      its aroma components.
AB  - The objective of this study is to identify the properties and responsible
      compounds for the aromatic roast odor (retort beef aroma) that commonly occurs in
      canned beef products and could contribute to their palatability. The optimal
      temperature for generating retort beef aroma was 121 degrees C. An untrained
      panel evaluated both uncured corned beef and canned yamato-ni beef and found that
      they had an aroma that was significantly (P < 0.01) similar to the odor of 121
      degrees C-heated beef than 100 degrees C-heated beef. The panel also noted that
      the aroma of 121 degrees C-heated beef tended to be (P < 0.1) preferable than
      that of 100 degrees C-heated beef. These results suggest that retort beef aroma
      is one constituent of palatability in canned beef. GC-MS (gas chromatography-mass
      spectrometry) analysis of the volatile fraction obtained from 100 degrees C- and
      121 degrees C-heated beef showed that the amounts of pyrazine, 2-methylpyrazine
      and diacetyl were higher in the 121 degrees C-heated beef than in the 100 degrees
      C-heated beef. GC-sniffing revealed that the odor quality of pyrazines was
      similar to that of retort beef aroma. Therefore, pyrazines were suggested to be a
      candidate responsible for the retort beef aroma. Analysis of commercial uncured
      corned beef and cured corned beef confirmed the presence of pyrazine, 2
      methylpyrazine and 2,6-dimethylpyrazine.

PMID- 28752558
TI  - Self-Assembled CoS Nanoflowers Wrapped in Reduced Graphene Oxides as the High
      Performance Anode Materials for Sodium-Ion Batteries.
AB  - It remains a big challenge to identify high-performance anode materials to
      promote practical applications of sodium-ion batteries. Herein, the facile
      synthesis of CoS nanoflowers wrapped in reduced graphene oxides (RGO) is
      reported, and their sodium storage properties are systematically studied in
      comparison with bare CoS. The CoS@RGO nanoflowers deliver a high reversible
      capacity of 620 mAh g-1 at a current density of 100 mA g-1 and superior rate
      capability with discharge capacity of 329 mAh g-1 at 4 A g-1 , much higher than
      those of the bare CoS. Evidenced by electrochemical impedance spectra and ex-situ
      SEM images, the improvement in the sodium storage performance is found to be due
      to the introduction of RGO which serves as a conducting matrix, to not only
      increase the kinetic properties of CoS, but also buffer the volume change and
      maintain the integrity of working electrodes during (de)sodiation processes. More
      importantly, the pseudocapacitive contribution of more than 89 % is only observed
      in the CoS@RGO nanocomposites, owing to the enhanced specific area and surface
      redox behavior.

PMID- 28752559
TI  - Catalytic, Reversible Arylation of Phosphines and Sulfides.
AB  - A fair exchange: Morandi and co-workers have reported a process that enables the
      exchange of aryl groups on sulfur or phosphorus. Building on established aryl
      transfer reactions, this Pd-catalyzed metathesis can be used to diversify
      thioanisoles and generate cyclic phosphines.

PMID- 28752560
TI  - Adherence with direct oral anticoagulants in nonvalvular atrial fibrillation new
      users and associated factors: a French nationwide cohort study.
AB  - PURPOSE: Direct oral anticoagulants (DOACs) have been promoted in patients with
      nonvalvular atrial fibrillation (nv-AF) as a more convenient alternative to
      vitamin K antagonists. We estimated 1-year dabigatran and rivaroxaban adherence
      rates in nv-AF patients and assessed associations between baseline patient
      characteristics and nonadherence. METHODS: This cohort study included OAC-naive
      nv-AF patients with no contraindications to OAC, who initiated dabigatran and
      rivaroxaban, using nationwide data from French national health care databases.
      One-year adherence was defined by the proportion of days covered of 80% or more
      over a fixed 1-year period after treatment initiation. Associations between
      nonadherence and baseline patient characteristics were assessed using
      multivariate logistic regression models. RESULTS: The population was composed of
      11 141 dabigatran (women: 48%; mean age: 74 +/- 10.7 y; >=80 y: 34.9%) and 11 126
      rivaroxaban (46.5%; 74 +/- 10.9 y; 34.8%) new users. One-year adherence was 53.3%
      in dabigatran-treated and 59.9% in rivaroxaban-treated patients, consistent with
      numerous subgroup analyses. A switch to vitamin K antagonist was observed in
      14.5% of dabigatran and 11.7% of rivaroxaban patients; 10.2% and 5.9% of patients
      switched to another DOAC, respectively; and 4.3% of patients died in the 2
      cohorts. In patients who did not die or switch during the follow-up, 1-year
      adherence was 69.6% in dabigatran-treated and 72.3% in rivaroxaban-treated
      patients. Having concomitant ischemic heart diseases was associated with an
      increased risk of nonadherence in the 2 cohorts. CONCLUSION: In this real-life
      study, 1-year adherence to DOAC is poor in nv-AF new users. Despite the
      introduction of DOAC, adherence to OACs may remain a significant challenge in AF
      patients.

PMID- 28752561
TI  - Preliminary evaluation of reflectance confocal microscopy features of scalp
      melanoma.

PMID- 28752562
TI  - Gas-phase chemical ionization of 4-alkyl branched-chain carboxylic acids and 3
      methylindole using H3 O+ , NO+ , and O2+ ions.
AB  - RATIONALE: 4-Methyloctanoic acid, 4-ethyloctanoic acid, 4-methylnonanoic acid,
      and 3-methylindole are primary contributors to the distinctive aroma and flavor
      of lamb meat. The reactions of H3 O+ , NO+ , and O2+ with these compounds, and
      identification of the product ions and their distribution, are fundamental to
      their characterization and rapid, real-time trace analysis using selected ion
      flow tube mass spectrometry (SIFT-MS). METHODS: The chemical ionization of pure
      standards of 4-ethyloctanoic acid, 4-methyloctanoic acid, 4-ethylnonanoic acid,
      and 3-methylindole was carried out using the H3 O+ , NO+ , and O2+ reagent ions
      of a V200TM SIFT mass spectrometer. Kinetic data were calculated using the
      Langevin collision rate with parameterized trajectory equations. Identification
      of product ions, distribution, and interferences was performed by further
      evaluation of the pertinent ion-molecule reaction mechanisms, careful spectral
      analyses, and molecular mass-molecular structure pairing. RESULTS: The
      collisional capture rate constants of the reaction of the precursor ions H3 O+ ,
      NO+ , and O2+ , their extended hydrates and the analytes, which were assumed to
      occur at or near the collisional rate, were all of the order of 10-9  cm3
      molecule s-1 - typical for bimolecular ion-molecule reactions. Positive
      identification of the primary and secondary product ions, fragmented ionic
      species, and potential ion conflicts and interferences, from each reagent ion
      channel, was determined for each compound. CONCLUSIONS: We have established the
      ion chemistry involved in the ionization of the 4-alkyl branched-chain fatty
      acids and 3-methylindole using the precursor ions, H3 O+ , NO+ , and O2+ in SIFT
      MS. The ion-molecular chemistry and the associated kinetics serve as a
      fundamental basis for the accurate characterization of these compounds by SIFT
      MS.

PMID- 28752563
TI  - Differential intestinal anti-inflammatory effects of Lactobacillus fermentum and
      Lactobacillus salivarius in DSS mouse colitis: impact on microRNAs expression and
      microbiota composition.
AB  - SCOPE: To compare the intestinal anti-inflammatory effects of two probiotics
      Lactobacillus fermentum and Lactobacillus salivarius in mouse colitis, focusing
      on their impact on selected miRNAs and microbiota composition. METHODS AND
      RESULTS: Male C57BL/6J mice were randomly assigned to four groups (n = 10): non
      colitic, DSS colitic and two colitic groups treated with probiotics (5 * 108
      CFU/mouse/day). Both probiotics ameliorated macroscopic colonic damage. They
      improved the colonic expression of markers involved in the immune response, and
      the expression of miR-155 and miR-223. L. fermentum also restored miR-150 and miR
      143 expression, also linked to the preservation of the intestinal barrier
      function. Besides, these beneficial effects were associated with the amelioration
      of the microbiota dysbiosis and a recovery of the SCFAs- and lactic acid
      producing bacterial populations, although only L. fermentum improved Chao
      richness, Pielou evenness and Shannon diversity. Moreover, L. fermentum also
      restored the Treg cell population in MLNs and the Th1/Th2 cytokine balance.
      CONCLUSION: Both probiotics exerted intestinal anti-inflammatory effects in DSS
      mouse colitis, maybe due to their ability to restore the intestinal microbiota
      homeostasis and modulate the immune response. L. fermentum showed a greater
      beneficial effect compared to L. salivarius, which makes it more interesting for
      future studies.

PMID- 28752564
TI  - Oral versus intravenous fluoropyrimidines for colorectal cancer.
AB  - BACKGROUND: Patients prefer oral to intravenous (IV) palliative chemotherapy,
      provided that oral therapy is not less effective. We compared the efficacy and
      safety of oral and IV fluoropyrimidines for treatment of colorectal cancer (CRC).
      OBJECTIVES: To compare the effects of oral and IV fluoropyrimidine chemotherapy
      in patients treated with curative or palliative intent for CRC. SEARCH METHODS:
      We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016,
      Issue 5), along with OVID MEDLINE, OVID Embase, and Web of Science databases, in
      June 2016. We also searched five clinical trials registers, several conference
      proceedings, and reference lists from study reports and systematic reviews. We
      contacted pharmaceutical companies to identify additional studies. SELECTION
      CRITERIA: We included randomised controlled trials (RCTs) comparing oral and IV
      fluoropyrimidine chemotherapy in patients treated with curative or palliative
      intent for CRC. DATA COLLECTION AND ANALYSIS: Three review authors extracted data
      and assessed risk of bias independently. We assessed the seven domains in the
      Cochrane 'Risk of bias' tool and three additional domains: schedules of outcome
      assessment and/or follow-up; use of intention-to-treat analysis; and baseline
      comparability of treatment arms. MAIN RESULTS: We included nine RCTs (total of
      10,918 participants) that examined treatment with curative intent for CRC with
      neoadjuvant and/or adjuvant chemotherapy. We included 35 RCTs (total of 12,592
      participants) that examined treatment with palliative intent for inoperable
      advanced or metastatic CRC with chemotherapy (31 first-line studies, two second
      line studies, and two studies of first- or second-line chemotherapy). All studies
      included male and female participants, and no studies included participants
      younger than 18 years of age. Patients treated with curative intent for CRC with
      neoadjuvant and/or adjuvant chemotherapy * Disease-free survival (DFS): DFS did
      not differ between participants treated with oral versus IV fluoropyrimidines
      (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.87 to 1.00; seven
      studies, 8903 participants; moderate-quality evidence).* Overall survival (OS):
      OS did not differ between participants treated with oral versus IV
      fluoropyrimidines (HR 0.92, 95% CI 0.84 to 1.00; seven studies, 8902 participants
      analysed; high-quality evidence).* Grade >= 3 adverse events (AEs): Participants
      treated with oral fluoropyrimidines experienced less grade >= 3
      neutropenia/granulocytopenia (odds ratio (OR) 0.14, 95% CI 0.11 to 0.16; seven
      studies, 8087 participants; moderate-quality evidence), stomatitis (OR 0.21, 95%
      CI 0.14 to 0.30; five studies, 4212 participants; low-quality evidence), and any
      grade >= 3 AEs (OR 0.82, 95% CI 0.74 to 0.90; five studies, 7741 participants;
      low-quality evidence). There was more grade >= 3 hand foot syndrome (OR 4.59, 95%
      CI 2.97 to 7.10; five studies, 5731 participants; low-quality evidence) in
      patients treated with oral fluoropyrimidines. There were no differences between
      participants treated with oral versus IV fluoropyrimidines in occurrence of grade
      >= 3 diarrhoea (OR 1.12, 95% CI 0.99 to 1.25; nine studies, 9551 participants;
      very low-quality evidence), febrile neutropenia (OR 0.59, 95% CI 0.18 to 1.90;
      four studies, 2925 participants; low-quality evidence), vomiting (OR 1.05, 95% CI
      0.83 to 1.34; eight studies, 9385 participants; low-quality evidence), nausea (OR
      1.21, 95% CI 0.97 to 1.51; seven studies, 9233 participants; low-quality
      evidence), mucositis (OR 0.64, 95% CI 0.25 to 1.62; four studies, 2233
      participants; very low-quality evidence), and hyperbilirubinaemia (OR 1.67, 95%
      CI 0.52 to 5.38; three studies, 2757 participants; very low-quality evidence).
      Patients treated with palliative intent for inoperable advanced or metastatic CRC
      with chemotherapy * Progression-free survival (PFS): Overall, PFS was inferior in
      participants treated with oral versus IV fluoropyrimidines (HR 1.06, 95% CI 1.02
      to 1.11; 23 studies, 9927 participants; moderate-quality evidence). Whilst PFS
      was worse in participants treated with oral compared with IV fluoropyrimidines
      when UFT/Ftorafur or eniluracil with oral 5-fluorouracil (5-FU) was used, PFS did
      not differ between individuals treated with oral versus IV fluoropyrimidines when
      capecitabine, doxifluridine, or S-1 was used.* OS: Overall, OS did not differ
      between participants treated with oral versus IV fluoropyrimidines (HR 1.02, 95%
      CI 0.99 to 1.05; 29 studies, 12,079 participants; high-quality evidence). OS was
      inferior in participants treated with oral versus IV fluoropyrimidines when
      eniluracil with oral 5-fluorouracil (5-FU) was used.* Time to progression (TTP):
      TTP was inferior in participants treated with oral versus IV fluoropyrimidines
      (HR 1.07, 95% CI 1.01 to 1.14; six studies, 1970 participants; moderate-quality
      evidence).* Objective response rate (ORR): ORR did not differ between
      participants treated with oral versus IV fluoropyrimidines (OR 0.98, 95% CI 0.90
      to 1.06; 32 studies, 11,115 participants; moderate-quality evidence).* Grade >= 3
      AEs: Participants treated with oral fluoropyrimidines experienced less grade >= 3
      neutropenia/granulocytopenia (OR 0.17, 95% CI 0.15 to 0.18; 29 studies, 11,794
      participants; low-quality evidence), febrile neutropenia (OR 0.27, 95% CI 0.21 to
      0.36; 19 studies, 9407 participants; moderate-quality evidence), stomatitis (OR
      0.26, 95% CI 0.20 to 0.33; 21 studies, 8718 participants; low-quality evidence),
      mucositis (OR 0.17, 95% CI 0.12 to 0.24; 12 studies, 4962 participants; low
      quality evidence), and any grade >= 3 AEs (OR 0.83, 95% CI 0.74 to 0.94; 14
      studies, 5436 participants; low-quality evidence). There was more grade >= 3
      diarrhoea (OR 1.66, 95% CI 1.50 to 1.84; 30 studies, 11,997 participants; low
      quality evidence) and hand foot syndrome (OR 3.92, 95% CI 2.84 to 5.43; 18
      studies, 6481 participants; moderate-quality evidence) in the oral
      fluoropyrimidine arm. There were no differences between oral and IV
      fluoropyrimidine arms in terms of grade >= 3 vomiting (OR 1.18, 95% CI 1.00 to
      1.40; 23 studies, 9528 participants; low-quality evidence), nausea (OR 1.16, 95%
      CI 0.99 to 1.36; 25 studies, 9796 participants; low-quality evidence), and
      hyperbilirubinaemia (OR 1.62, 95% CI 0.99 to 2.64; nine studies, 2699
      participants; low-quality evidence). AUTHORS' CONCLUSIONS: Results of this review
      should provide confidence that treatment for CRC with most of the oral
      fluoropyrimidines commonly used in current clinical practice is similarly
      efficacious to treatment with IV fluoropyrimidines. Treatment with eniluracil
      with oral 5-FU was associated with inferior PFS and OS among participants treated
      with palliative intent for CRC, and eniluracil is no longer being developed. Oral
      and IV fluoropyrimidines have different patterns of side effects; future research
      may focus on determining the basis for these differences.

PMID- 28752565
TI  - The relationship between subcortical brain volume and striatal dopamine D2/3
      receptor availability in healthy humans assessed with [11 C]-raclopride and [11
      C]-(+)-PHNO PET.
AB  - BACKGROUND: Abnormalities in dopamine (DA) and brain morphology are observed in
      several neuropsychiatric disorders. However, it is not fully understood how these
      abnormalities may relate to one another. For such in vivo findings to be used as
      biomarkers for neuropsychiatric disease, it must be understood how variability in
      DA relates to brain structure under healthy conditions. We explored how the
      availability of striatal DA D2/3 receptors (D2/3 R) is related to the volume of
      subcortical brain structures in a sample of healthy humans. Differences in D2/3 R
      availability measured with an antagonist radiotracer ([11 C]-raclopride) versus
      an agonist radiotracer ([11 C]-(+)-PHNO) were examined. METHODS: Data from 62
      subjects scanned with [11 C]-raclopride (mean age = 38.98 +/- 14.45; 23 female)
      and 68 subjects scanned with [11 C]-(+)-PHNO (mean age = 38.54 +/- 14.59; 25
      female) were used. Subcortical volumes were extracted from T1-weighted images
      using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm.
      Partial correlations were used controlling for age, gender, and total brain
      volume. RESULTS: For [11 C]-(+)-PHNO, ventral caudate volumes were positively
      correlated with BPND in the dorsal caudate and globus pallidus (GP). Ventral
      striatum (VS) volumes were positively correlated with BPND in the VS. With [11 C]
      raclopride, BPND in the VS was negatively correlated with subiculum volume of the
      hippocampus. Moreover, BPND in the GP was negatively correlated with the volume
      of the lateral posterior nucleus of the thalamus. CONCLUSION: Findings are purely
      exploratory and presented corrected and uncorrected for multiple comparisons. We
      hope they will help inform the interpretation of future PET studies where
      concurrent changes in D2/3 R and brain morphology are observed. Hum Brain Mapp
      38:5519-5534, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28752566
TI  - Impaired insulin clearance as a cause rather than a consequence of insulin
      resistance.

PMID- 28752567
TI  - Auditory-visual integration modulates location-specific repetition suppression of
      auditory responses.
AB  - Space is a dimension shared by different modalities, but at what stage spatial
      encoding is affected by multisensory processes is unclear. Early studies observed
      attenuation of N1/P2 auditory evoked responses following repetition of sounds
      from the same location. Here, we asked whether this effect is modulated by
      audiovisual interactions. In two experiments, using a repetition-suppression
      paradigm, we presented pairs of tones in free field, where the test stimulus was
      a tone presented at a fixed lateral location. Experiment 1 established a neural
      index of auditory spatial sensitivity, by comparing the degree of attenuation of
      the response to test stimuli when they were preceded by an adapter sound at the
      same location versus 30 degrees  or 60 degrees  away. We found that the degree of
      attenuation at the P2 latency was inversely related to the spatial distance
      between the test stimulus and the adapter stimulus. In Experiment 2, the adapter
      stimulus was a tone presented from the same location or a more medial location
      than the test stimulus. The adapter stimulus was accompanied by a simultaneous
      flash displayed orthogonally from one of the two locations. Sound-flash
      incongruence reduced accuracy in a same-different location discrimination task
      (i.e., the ventriloquism effect) and reduced the location-specific repetition
      suppression at the P2 latency. Importantly, this multisensory effect included
      topographic modulations, indicative of changes in the relative contribution of
      underlying sources across conditions. Our findings suggest that the auditory
      response at the P2 latency is affected by spatially selective brain activity,
      which is affected crossmodally by visual information.

PMID- 28752569
TI  - The first phlebo-like virus infecting plants: a case study on the adaptation of
      negative-stranded RNA viruses to new hosts.
AB  - A novel negative-stranded (ns) RNA virus associated with a severe citrus disease
      reported more than 80 years ago has been identified. Transmission electron
      microscopy showed that this novel virus, tentatively named citrus concave gum
      associated virus, is flexuous and non-enveloped. Notwithstanding, its two genomic
      RNAs share structural features with members of the genus Phlebovirus, which are
      enveloped arthropod-transmitted viruses infecting mammals, and with a group of
      still unclassified phlebo-like viruses mainly infecting arthropods. CCGaV genomic
      RNAs code for an RNA-dependent RNA polymerase, a nucleocapsid protein and a
      putative movement protein showing structural and phylogenetic relationships with
      phlebo-like viruses, phleboviruses and the unrelated ophioviruses, respectively,
      thus providing intriguing evidence of a modular genome evolution. Phylogenetic
      reconstructions identified an invertebrate-restricted virus as the most likely
      ancestor of this virus, revealing that its adaptation to plants was independent
      from and possibly predated that of the other nsRNA plant viruses. These data are
      consistent with an evolutionary scenario in which trans-kingdom adaptation
      occurred several times during the history of nsRNA viruses and followed different
      evolutionary pathways, in which genomic RNA segments were gained or lost. The
      need to create a new genus for this bipartite nsRNA virus and the impact of the
      rapid and specific detection methods developed here on citrus sanitation and
      certification are also discussed.

PMID- 28752568
TI  - IDUA mutational profile and genotype-phenotype relationships in UK patients with
      Mucopolysaccharidosis Type I.
AB  - Mucopolysaccharidosis Type I (MPS I) is a lysosomal storage disorder with varying
      degrees of phenotypic severity caused by mutations in IDUA. Over 200 disease
      causing variants in IDUA have been reported. We describe the profile of disease
      causing variants in 291 individuals with MPS I for whom IDUA sequencing was
      performed, focusing on the UK subset of the cohort. A total of 63 variants were
      identified, of which 20 were novel, and the functional significance of the novel
      variants is explored. The severe form of MPS I is treated with hematopoietic stem
      cell transplantation, known to have improved outcomes with earlier age at
      treatment. Developing genotype-phenotype relationships would therefore have
      considerable clinical utility, especially in the light of the development of
      newborn screening programs for MPS I. Associations between genotype and phenotype
      are examined in this cohort, particularly in the context of the profile of
      variants identified in UK individuals. Relevant associations can be made for the
      majority of UK individuals based on the presence of nonsense or truncating
      variants as well as other associations described in this report.

PMID- 28752570
TI  - A preliminary comparison of two-dimensional speckle tracking echocardiography and
      pressure-volume loop analysis in patients with Fontan physiology: The role of
      ventricular morphology.
AB  - OBJECTIVE: Speckle tracking echocardiography (STE) may be a useful modality for
      assessing ventricular performance in patients with single ventricle physiology.
      However, STE's ability to accurately assess ventricular performance in this
      population is unknown. The objective of this study was to perform a preliminary
      comparison of STE measures of myocardial deformation to reference standard
      measures of function derived from pressure-volume loop (PVL) analysis. DESIGN:
      This was a secondary analysis of a prospective study investigating PVLs in
      patients with Fontan physiology. PVLs were recorded using microconductance
      catheters. PVL indices included end-systolic elastance (Ees), arterial elastance
      (Ea), ventriculo-arterial coupling (Ea/Ees), and the isovolumic relaxation time
      constant (tau). Patients were included if they had an echocardiogram within 1
      month of their catheterization. STE was performed retrospectively using vendor
      independent software. RESULTS: Seventeen patients had echocardiograms available
      for analysis, 12 were right ventricular (RV) dominant. The median age was 8 years
      (IQR 5-17 years). Circumferential strain (r=-.72, P<=.01) and strain rate (r=
      .61, P=.04) correlated with Ea/Ees in those with RV-dominant morphology.
      Longitudinal strain rate correlated with Ees in those with LV-dominant morphology
      (r=-.98, P<=.01). Longitudinal EDSR correlated with tau in those with LV-dominant
      morphology (r=-.90, P=.04). CONCLUSIONS: In this limited sample, circumferential
      measures of deformation correlated with PVL measures better in patients with RV
      morphology, while longitudinal measures correlated better with PVL measures in
      patients with LV morphology. Further validation and investigation into the
      clinical usefulness of these measures are warranted.

PMID- 28752571
TI  - Haematopoietic stem cell transplantation for primary immunodeficiency syndromes:
      A 5-year single-centre experience.
AB  - AIM: Haematopoietic stem cell transplantation (HSCT) is a central therapy in the
      treatment of primary immunodeficiency diseases (PIDs). Over the past 5 years,
      outcomes have been greatly improved due to earlier diagnosis, improved donor
      availability, advancements in graft manipulation and the use of less toxic
      preparative regimens. We present a 5-year audit of HSCT for PID at a single
      Australian tertiary hospital. METHODS: Retrospective case note review identified
      diagnosis, pre-transplant medical morbidity, transplant protocol, engraftment,
      adverse events, post-transplant immune reconstitution and general health.
      RESULTS: A total of 22 patients with PID underwent 24 HSCTs at our institution
      between 2012 and 2016. The most common indications were severe combined
      immunodeficiency, chronic granulomatous disease and familial haemophagocytic
      lymphohistiocytosis, with a genetic diagnosis in all but two patients. Reduced
      intensity or reduced toxicity conditioning was used in 91% of cases, and 75% of
      the donors were unrelated. Transplant-related mortality at day +100 was 9.5%, and
      cumulative overall survival was 86%. There were three mortalities, all secondary
      to viral infection, one of which occurred in the context of graft failure. Two
      patients remained on immune support, with the remainder achieving adequate immune
      reconstitution. CONCLUSIONS: The outcomes for HSCT for PIDs performed at Sydney
      Children's Hospital were in line with the world's best practice. HSCT should be
      considered a potential therapeutic option for all Australian PID patients with a
      valid disease indication.

PMID- 28752572
TI  - Effect of paracetamol on semen quality.
AB  - Several published studies, both direct and indirect, have connected paracetamol,
      also named acetaminophen, a commonly used over-the-counter analgesic and
      antipyretic medication, with semen quality and male infertility, although as yet
      this connection is unclear. This review addresses the effect of paracetamol on
      semen quality and hence on male factor infertility. We searched the MEDLINE
      database from January 1980 through January 2017 for English-language articles
      using the key words "paracetamol" and "acetaminophen" versus "sperm." References
      from articles were used only if relevant. In summary, paracetamol, when used at
      high doses, appears to change semen quality, particularly sperm morphology, and
      hence its fertilising ability. Such effect of paracetamol on semen quality may
      occur by suppressing testosterone synthesis, inducing oxidative stress, provoking
      apoptosis of spermatocytes, reducing nitric oxide production and inhibiting
      prostaglandin synthesis. Further research, particularly clinical research, will
      be very important to confirm these effects.

PMID- 28752573
TI  - Adiponectin exerts a potent anti-arthritic effect and insulin resistance in
      collagen-induced arthritic rats.
AB  - AIM: Previous research has shown that adiponectin (AD) induces severe insulin
      resistance (IR) and exhibits pro-inflammatory effect, so it could serve as a
      useful risk biomarker in rheumatoid arthritis (RA). The present study aims to
      evaluate the effect of AD on IR and anti-arthritis in collagen-induced arthritic
      (CIA) rats. METHOD: After immunization with bovine type II collagen (CII), Wistar
      rats were administered with AD (60 MUg/kg/day) or saline into the ankle joint
      cavity of the left hind leg for 15 days. The severity of arthritis was clinically
      and histologically assessed. Arthritis score was recorded every other day for
      each paw. Paw volume was measured on alternate days to monitor the progression of
      the disease in the arthritic control group. Tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-1, AD, insulin and fasting glucose were measured in sera.
      Histopathology of joint synovial tissues was also examined. RESULTS: Treatment
      with AD resulted in significantly delayed onset of arthritis as well as decreased
      clinical arthritis and histopathological severity scores. AD reduced both serum
      fasting glucose, TNF-alpha, IL-1 and IR. Histological analysis confirmed
      treatment with AD suppressed joint synovial inflammation and immunohistochemical
      expression of TNF-alpha compared to the CIA group. Surprisingly, adiponectin
      levels measured by enzyme-linked immunosorbent assay in serum were significantly
      increased in CIA rats compared to the normal group. CONCLUSIONS: Adiponectin
      might display anti-inflammatory effects. These results suggest that AD may be a
      potential immunosuppressant for the treatment of RA linked to metabolic disease.

PMID- 28752574
TI  - Improved sensitivity of firefly luminescent intermediate-based protein
      interaction assay using Ser 440 mutant with lower adenylation activity.
AB  - Protein-protein interaction assays are important in various fields including
      molecular biology, diagnostics, and drug screening. We recently designed a novel
      protein-protein interaction assay, the firefly luminescent intermediate-based
      protein interaction assay (FlimPIA), that exploited the unique reaction mechanism
      of firefly luciferase (Fluc). Using two mutant Flucs, each impaired with one of
      the two half-reactions, namely adenylation and subsequent oxidative luminescent
      steps, FlimPIA detects the proximity of the two proteins tethered to the mutant
      Flucs. Here, we found that introducing a mutation into a residue in the hinge
      region (S440) of the mutant with lowered adenylation activity ('Acceptor' Fluc)
      further improved the response of FlimPIA by lowering the residual adenylation
      activity. Mutants with bulkier residues showed greater inhibition, probably due
      to increased steric hindrance at the adenylation conformation. As a result, the
      FlimPIA with S440 L acceptor showed the best signal/background ratio for the
      detection of rapamycin-induced FKBP12-FRB interactions.

PMID- 28752575
TI  - IPL vs PDL in treatment of facial erythema: A split-face study.
AB  - BACKGROUND: Lasers and noncoherent intense pulse light sources effectively treat
      vascular lesions. Intense pulsed light (IPL), a nonablative treatment for
      photorejuvenation, uses a flashlamp which emits noncoherent light between 400 and
      1400 nm. The light may be filtered to target a specific chromophore. The pulsed
      dye laser (PDL), at 595 nm, has been the historical standard of care in the
      treatment of facial erythema. We sought to determine whether IPL may be used in
      lieu of PDL in reducing facial erythema. OBJECTIVES: To determine whether IPL may
      be used to treat facial erythema with equal efficacy as PDL used at nonpurpuric
      settings. METHODS: Prospective investigation of a cohort of 15 subjects with
      unwanted bilateral facial erythema. Subjects presented for two treatments with an
      IPL (BBLTM BroadBand Light; Sciton, Palo Alto, CA) to one half of the face and
      PDL (CynergyTM; Cynosure, Westford, MA) to the other half. RESULTS: Patients with
      facial erythema may be successfully treated with IPL or PDL. CONCLUSIONS: Intense
      pulsed light and pulsed dye laser with nonpurpuric settings were equally
      effective in reducing facial erythema.

PMID- 28752576
TI  - Influence of Prostanoids in the Diuretic and Natriuretic Effects of Extracts and
      Kaempferitrin from Bauhinia forficata Link Leaves in Rats.
AB  - Although Bauhinia forficata Link is popularly used in Brazil to induce diuresis,
      no scientific investigation has focused on demonstrating its efficacy in
      preclinical trials. For that, normotensive male Wistar and spontaneously
      hypertensive rats were used to test the effect of extracts and kaempferitrin
      obtained from Bauhinia forficata leaves in the experimental model of diuresis.
      Cumulative urine volume, Na+ and K+ excretion, calcium, creatinine, prostaglandin
      E2 , pH, density, and conductivity were measured at the end of the experiment
      (after 8 or 24 h). The treatment with aqueous infusion, methanolic extract,
      trichloromethane, or ethyl acetate-butanolic fractions significantly increase
      urinary volume and electrolytes levels when orally given to rats, without
      altering the pH or density parameters. Kaempferitrin induced diuretic,
      natriuretic, but not kaliuretic effects in both normotensive and hypertensive
      rats. In addition, kaempferitrin enhanced urinary creatinine and prostaglandin E2
      excretion, without modifying calcium levels. Kaempferitrin-induced diuresis was
      unaffected by previous treatment with a nonselective inhibitor of nitric oxide
      synthase and neither with a nonselective muscarinic receptor antagonist. On the
      other hand, a cyclooxygenase inhibitor was able to decrease its effect when
      compared with vehicle-treated rats, suggesting that the diuretic and natriuretic
      properties from kaempferitrin are associated with endogenous prostanoids
      generation. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28752577
TI  - Extent, quality and impact of patient and public involvement in antimicrobial
      drug development research: A systematic review.
AB  - BACKGROUND: Patient and public involvement (PPI) is increasingly recognized as
      bringing a range of benefits to clinical and health services research. Recent
      systematic reviews have identified and synthesized many benefits (eg higher
      recruitment rates) and some costs (eg extra time need). Much of the literature
      focuses on PPI in long-term conditions rather than more acute health care in
      which the majority of microbiological research is undertaken. OBJECTIVES: The aim
      was to identify the extent, quality and impact of PPI in antimicrobial drug
      development research. Objectives were to identify any relevant reporting of PPI
      in antimicrobial research; appraise the quality of reporting on PPI using
      recognized PPI reporting and critical appraisal tools; and extract and synthesize
      data on the impact of PPI. SEARCH STRATEGY: A systematic review was undertaken
      with a search strategy based on four word groups (PPI, patients, antimicrobial
      drug development and outcomes). Eight online databases were searched. INCLUSION
      CRITERIA: English language publication, publication between 1996 and 2016 and
      studies describing PPI in antimicrobial drug development research. MAIN RESULTS:
      No studies were found through online searching that met the search strategy and
      inclusion criteria. One relevant protocol paper with a brief mention of PPI was
      identified through expert recommendation. Commentary papers recommending PPI were
      identified through website searching and expert opinion. DISCUSSION AND
      CONCLUSIONS: Despite strong policy guidance encouraging PPI at the international
      and national levels, and anecdotal accounts of PPI taking place, evidence for the
      extent, quality and impact of PPI in antimicrobial drug development research has
      not yet appeared in the peer-reviewed literature.

PMID- 28752578
TI  - Ultrathin Two-Dimensional Multinary Layered Metal Chalcogenide Nanomaterials.
AB  - Ultrathin two-dimensional (2D) layered transition metal dichalcogenides (TMDs),
      such as MoS2 , WS2 , TiS2 , TaS2 , ReS2 , MoSe2 and WSe2 , have attracted
      considerable attention over the past six years owing to their unique properties
      and great potential in a wide range of applications. Aiming to achieve tunable
      properties and optimal application performances, great effort is devoted to the
      exploration of 2D multinary layered metal chalcogenide nanomaterials, which
      include ternary metal chalcogenides with well-defined crystal structures, alloyed
      TMDs, heteroatom-doped TMDs and 2D metal chalcogenide heteronanostructures. These
      novel 2D multinary layered metal chalcogenide nanomaterials exhibit some unique
      properties compared to 2D binary TMD counterparts, thus holding great promise in
      various potential applications including electronics/optoelectronics, catalysis,
      sensors, biomedicine, and energy storage and conversion with enhanced
      performances. This article focuses on the state-of-art progress on the
      preparation, characterization and applications of ultrathin 2D multinary layered
      metal chalcogenide nanomaterials.

PMID- 28752579
TI  - Osteoarthritic human chondrocytes proliferate in 3D co-culture with mesenchymal
      stem cells in suspension bioreactors.
AB  - Osteoarthritis (OA) is a painful disease, characterized by progressive surface
      erosion of articular cartilage. The use of human articular chondrocytes (hACs)
      sourced from OA patients has been proposed as a potential therapy for cartilage
      repair, but this approach is limited by the lack of scalable methods to produce
      clinically relevant quantities of cartilage-generating cells. Previous studies in
      static culture have shown that hACs co-cultured with human mesenchymal stem cells
      (hMSCs) as 3D pellets can upregulate proliferation and generate neocartilage with
      enhanced functional matrix formation relative to that produced from either cell
      type alone. However, because static culture flasks are not readily amenable to
      scale up, scalable suspension bioreactors were investigated to determine if they
      could support the co-culture of hMSCs and OA hACs under serum-free conditions to
      facilitate clinical translation of this approach. When hACs and hMSCs (1:3 ratio)
      were inoculated at 20,000 cells/ml into 125-ml suspension bioreactors and fed
      weekly, they spontaneously formed 3D aggregates and proliferated, resulting in a
      4.75-fold increase over 16 days. Whereas the apparent growth rate was lower than
      that achieved during co-culture as a 2D monolayer in static culture flasks,
      bioreactor co-culture as 3D aggregates resulted in a significantly lower collagen
      I to II mRNA expression ratio and more than double the glycosaminoglycan/DNA
      content (5.8 vs. 2.5 MUg/MUg). The proliferation of hMSCs and hACs as 3D
      aggregates in serum-free suspension culture demonstrates that scalable
      bioreactors represent an accessible platform capable of supporting the generation
      of clinical quantities of cells for use in cell-based cartilage repair.

PMID- 28752580
TI  - A randomized controlled trial comparing EMDR and CBT for obsessive-compulsive
      disorder.
AB  - BACKGROUND: This study aimed to evaluate eye movement desensitization and
      reprocessing (EMDR) as a treatment for obsessive-compulsive disorder (OCD), by
      comparison to cognitive behavioural therapy (CBT) based on exposure and response
      prevention. METHOD: This was a pragmatic, feasibility randomized controlled trial
      in which 55 participants with OCD were randomized to EMDR (n = 29) or CBT (n =
      26). The Yale-Brown obsessive-compulsive scale was completed at baseline, after
      treatment and at 6 months follow-up. Treatment completion and response rates were
      compared using chi-square tests. Effect size was examined using Cohen's d and
      multilevel modelling. RESULTS: Overall, 61.8% completed treatment and 30.2%
      attained reliable and clinically significant improvement in OCD symptoms, with no
      significant differences between groups (p > .05). There were no significant
      differences between groups in Yale-Brown obsessive-compulsive scale severity post
      treatment (d = -0.24, p = .38) or at 6 months follow-up (d = -0.03, p = .90).
      CONCLUSIONS: EMDR and CBT had comparable completion rates and clinical outcomes.

PMID- 28752581
TI  - Direct and Selective Synthesis of Hydrogen Peroxide over Palladium-Tellurium
      Catalysts at Ambient Pressure.
AB  - Highly selective hydrogen peroxide (H2 O2 ) synthesis directly from H2 and O2 is
      a strongly desired reaction for green processes. Herein a highly efficient
      palladium-tellurium (Pd-Te/TiO2 ) catalyst with a selectivity of nearly 100 %
      toward H2 O2 under mild conditions (283 K, 0.1 MPa, and a semi-batch continuous
      flow reactor) is reported. The size of Pd particles was remarkably reduced from
      2.1 nm to 1.4 nm with the addition of Te. The Te-modified Pd surface could
      significantly weaken the dissociative activation of O2 , leading to the non
      dissociative hydrogenation of O2 . Density functional theory calculations
      illuminated the critical role of Te in the selective hydrogenation of O2 , in
      that the active sites composed of Pd and Te could significantly restrain side
      reactions. This work has made significant progress on the development of high
      selectivity catalysts for the direct synthesis of H2 O2 at ambient pressure.

PMID- 28752582
TI  - Aspects of control and substance use among middle-aged and older adults with
      bipolar disorder.
AB  - High prevalence rates of alcohol and substance use disorders have been reported
      among persons with bipolar disorder (BD). In the present study, we explored the
      daily experiences of middle-aged and older adults living with BD who reported
      regular substance use and the ways in which participants expressed 'control' in
      relation to their use of alcohol and other substances. Semistructured, in-depth
      interviews were conducted with 12 participants (nine women and three men), aged
      36-57 years of age (mean = 49 years). Thematic analyses identified emergent
      themes and patterns in participants' life histories. The theme of 'control'
      emerged as central to participants' reports, and was organized into four
      categories: (i) substance use to control BD symptoms; (ii) substance use provides
      a sense of being in control; (iii) methods of controlled substance use; and (iv)
      not having control: overreliance on substances. Implications of the present study
      include the need for nurses to openly discuss the use of alcohol and other drugs
      with persons with BD, provide health information and screening, and determine
      whether persons with BD feel they have control over their substance use. Several
      lines of research with persons who have BD and use substances are suggested.

PMID- 28752583
TI  - Supramolecular Polymerization from Controllable Fabrication to Living
      Polymerization.
AB  - Supramolecular polymers have attracted plenty of interest in the scientific
      community; however, developing controllable methods of supramolecular
      polymerization remains a serious challenge. This article reviews some recent
      developments of methods for supramolecular polymerization from controllable
      fabrication to living polymerization. Three facile methods with general
      applicability for controllable fabrication of supramolecular polymers have been
      established recently: the first method is a self-sorting approach by manipulating
      ring-chain equilibrium based on noncovalent control over rigidity of monomers;
      the second is covalent polymerization from supramonomers formed by noncovalent
      interactions; and the third is supramolecular interfacial polymerization. More
      excitingly, living supramolecular polymerization has been achieved by two elegant
      strategies, including seeded supramolecular polymerization under pathway
      complexity control and chain-growth supramolecular polymerization by metastable
      monomers. It is anticipated that this review may provide some guidance for
      precise fabrication of supramolecular polymers, leading to the construction of
      supramolecular polymeric materials with controllable architectures and functions.

PMID- 28752584
TI  - Age-related shifts in hemispheric dominance for syntactic processing.
AB  - Recent ERP data from young adults have revealed that simple syntactic anomalies
      elicit different patterns of lateralization in right-handed participants
      depending upon their familial sinistrality profile (whether or not they have left
      handed biological relatives). Right-handed participants who do not have left
      handed relatives showed a strongly lateralized response pattern, with P600
      responses following left-hemisphere-biased presentations and N400 responses
      following right-hemisphere-biased presentations. Given that the literature on
      aging has documented a tendency to change across adulthood from asymmetry of
      function to a more bilateral pattern, we tested the stability of this asymmetric
      response to syntactic violations by recording ERPs as 24 older adults (age 60+)
      with no history of familial sinistrality made grammaticality judgments on simple
      two-word phrases. Results showed that the asymmetric pattern observed in right
      handed adults without familial sinistrality indeed changes with age, such that
      P600 responses come to be elicited not only with left-hemisphere-biased but also
      with right-hemisphere-biased presentations in older adults. These findings
      suggest that, as with many other cognitive functions, syntactic processing
      becomes more bilateral with age.

PMID- 28752585
TI  - Endoscopic identification of a laryngeal anaplastic sarcoma in a pet rabbit.

PMID- 28752586
TI  - Bone mineral density profile among post-menopausal women in Manipur: a hospital
      based study - methodological issues.

PMID- 28752587
TI  - Unexpected resilience of a seagrass system exposed to global stressors.
AB  - Despite a growing interest in identifying tipping points in response to
      environmental change, our understanding of the ecological mechanisms underlying
      nonlinear ecosystem dynamics is limited. Ecosystems governed by strong species
      interactions can provide important insight into how nonlinear relationships
      between organisms and their environment propagate through ecosystems, and the
      potential for environmentally mediated species interactions to drive or protect
      against sudden ecosystem shifts. Here, we experimentally determine the functional
      relationships (i.e., the shapes of the relationships between predictor and
      response variables) of a seagrass assemblage with well-defined species
      interactions to ocean acidification (enrichment of CO2 ) in isolation and in
      combination with nutrient loading. We demonstrate that the effect of ocean
      acidification on grazer biomass (Phyllaplysia taylori and Idotea resecata) was
      quadratic, with the peak of grazer biomass at mid-pH levels. Algal grazing was
      negatively affected by nutrients, potentially due to low grazer affinity for
      macroalgae (Ulva intestinalis), as recruitment of both macroalgae and diatoms
      were favored in elevated nutrient conditions. This led to an exponential increase
      in macroalgal and epiphyte biomass with ocean acidification, regardless of
      nutrient concentration. When left unchecked, algae can cause declines in seagrass
      productivity and persistence through shading and competition. Despite quadratic
      and exponential functional relationships to stressors that could cause a
      nonlinear decrease in seagrass biomass, productivity of our model seagrass-the
      eelgrass (Zostera marina)- remained highly resilient to increasing acidification.
      These results suggest that important species interactions governing ecosystem
      dynamics may shift with environmental change, and ecosystem state may be
      decoupled from ecological responses at lower levels of organization.

PMID- 28752588
TI  - Psychological adjustment and behaviours in children of migrant workers in China.
AB  - BACKGROUND: In China, there are around 274 million rural-urban migrants, an
      estimated 61 million children left behind in rural areas by parents, and 29
      million children who accompany their parents to cities. The aim of this study was
      to compare the psychosocial adjustment and behaviours of left-behind children and
      migrant children. METHODS: Full data were available for 761 left-behind children
      and 1,392 migrant children aged 11 to 17 in Zhejiang Province, eastern China.
      Participants completed a questionnaire focusing on migration status, risks
      behaviours, and psychological well-being, measured with the Strengths and
      Difficulties Questionnaire. RESULTS: There were more left behind girls and more
      urban migrant boys (p < .001). The mean scores on the Strengths and Difficulties
      Questionnaire were all higher in left-behind children than migrant children: for
      emotional symptoms (3.82 vs. 3.03, p < .001), conduct problems (2.55 vs. 2.41, p
      = .048), hyperactivity (4.25 vs. 3.81, p < .001), and total difficulties (13.46
      vs. 12.00, p = .020), whereas the prosocial score was lower (6.68 vs. 6.90, p <
      .001), all indicating lower levels of well-being in left-behind children.
      Overall, 11.4% of left-behind children and 8.8% of migrant children scored in the
      abnormal range for total difficulties. Left behind girls were particularly
      vulnerable to emotional problems. Left-behind children were more likely to admit
      to stealing and cheating on exams, but there were no differences in other risks
      behaviours, such as smoking and drinking. CONCLUSIONS: Migration with parents,
      rather than separation from parents, was associated with better psychological
      well-being and fewer behavioural problems. Our findings have relevance for
      migrant parents in helping to inform decisions about where to raise their
      children as well as for policymakers in countries where migration is a major
      issue. When children are left behind, models of community support need to be
      considered, especially for those who are most vulnerable.

PMID- 28752589
TI  - Frailty and Potentially Inappropriate Medication Use at Nursing Home Transition.
AB  - BACKGROUND/OBJECTIVES: To estimate the prevalence of potentially inappropriate
      medication (PIM) use among older adults with cognitive impairment or dementia
      prior to and following admission to nursing homes and in relation to frailty.
      DESIGN: Retrospective cohort study using health administrative databases.
      SETTING: Ontario, Canada. PARTICIPANTS: 41,351 individuals with cognitive
      impairment or dementia, aged 66+ years newly admitted to nursing home between
      2011 and 2014. MEASUREMENTS: PIMs were defined with 2015 Beers Criteria and
      included antipsychotics, H2 -receptor antagonists, benzodiazepines, and drugs
      with strong anticholinergic properties. Medication information was obtained at
      nursing home admission and in the subsequent 180 days. Multivariable Cox
      proportional-hazards models were used to assess the impact of frailty status
      (determined by a 72-item frailty index) on the hazard of starting and
      discontinuing PIMs. RESULTS: At admission, 44% of residents with cognitive
      impairment or dementia were on a PIM and prevalence varied by frailty (38.7% non
      frail, 42.8% pre-frail, and 48.1% frail, P < .001). Following admission, many
      residents discontinued PIMs (23.5% for antipsychotics, 49.3% benzodiazepines,
      32.2% anticholinergics, and 30.9% H2 -receptor antagonists). However, PIMs were
      also introduced with 10.9% newly started on antipsychotics, benzodiazepines
      (10.1%), anticholinergics (6.6%), and H2 -receptor antagonists (1.2%). After
      adjustment for other characteristics, frail residents had a similar risk of PIM
      discontinuation as non-frail residents except for anticholinergics (HR = 1.21,
      95% CI 1.06-1.39) but were more likely to be newly prescribed benzodiazepines (HR
      = 1.32, 95% CI 1.20-1.44), antipsychotics (HR = 1.36, 1.23-1.49), and
      anticholinergics (HR = 1.34, 95% CI 1.20-1.50). CONCLUSION: Many residents with
      cognitive impairment or dementia enter nursing homes on PIMs. PIMs are more
      likely to be started in frail individuals following admission. Interventions to
      support deprescribing of PIMs should be implemented targeting frail individuals
      during the transition to nursing home.

PMID- 28752590
TI  - Comparison of the G and V methods for ventrogluteal site identification: Muscle
      and subcutaneous fat thicknesses and considerations for successful intramuscular
      injection.
AB  - The ventrogluteal site is increasingly recommended for long-acting antipsychotic
      intramuscular injections; however, it remains infrequently utilized due to
      nurses' lack of confidence in site identification. The more recent G (geometric)
      method of ventrogluteal site identification is less subjective and likely more
      reliable than the V method for successful intramuscular injection outcomes.
      Knowledge of muscle and subcutaneous fat thicknesses, and the influence of sex
      and anthropometry on theoretical injection outcome, is necessary to support
      evidence-based use of the ventrogluteal site. In the presents study, we compared
      the V and G methods for injection site subcutaneous fat, muscle, and total tissue
      thicknesses, and theoretical injection outcome (bone injury, intramuscular or
      subcutaneous), and determined anthropometric predictors of injection outcome.
      Subcutaneous fat and muscle thicknesses were measured via ultrasound, bilaterally
      at V and G method sites (28 males, 32 females). Muscle and total tissue were
      significantly thicker, and successful intramuscular injection significantly more
      likely, using the G versus V method (75% versus 57%). Females had significantly
      thicker subcutaneous fat than males at both sites. Even using the G method, 92%
      of males but only 59% of females, would have a successful intramuscular
      injection, with remaining females at risk of bone injury (16%) or subcutaneous
      injection (25%). The G method site is more reliable for successful intramuscular
      injection, with less risk of bone injury than the V method site. Appropriate
      needle-length selection is essential for females with a body mass index (BMI) <23
      kg m-2 and weight <60 kg (to avoid bone injury), and BMI >30 kg m-2 and hip >90
      cm (to avoid subcutaneous injection).

PMID- 28752591
TI  - Comparison and evaluation of capacitation and acrosomal reaction in freeze-thawed
      human ejaculated spermatozoa treated with L-carnitine and pentoxifylline.
AB  - Cryopreservation is used to preserve the spermatozoa; however, it leads to a
      reduction in sperm quality. L-carnitine (LC) influences sperm motility and
      preserves the sperm membrane and DNA integrity. The objectives of this study were
      to evaluate the protective effects of LC on the membrane integrity of normal
      human spermatozoa and compare it with pentoxifylline (PT) during
      cryopreservation. Thirty normal semen samples, prepared by swim-up procedure,
      were divided into three aliquots: a control without any treatment and two
      experimental aliquots that were incubated in PT or LC for 30 min. All aliquots
      were cryopreserved and thawed after 48 hr. To evaluate the percentages of intact,
      acrosomal-reacted and capacitated spermatozoa, lectin histochemistry and flow
      cytometry were performed by wheat germ agglutinin, peanut agglutinin and Con A.
      Statistical analyses were performed using ANOVA. LC supplementation elevated the
      percentage of noncapacitated spermatozoa compared with control and PT-treated
      samples and the percentages of acrosomal intact spermatozoa compared with PT
      treated samples. PT pre-treatment improved the motility but not membrane
      integrity. LC supplementation reduced the percentages of acrosomal-reacted
      spermatozoa compared with the control and PT-treated samples. Although LC did not
      improve motility, it protected the plasma membrane and acrosomal integrity.
      Therefore, LC may be the superior choice compared to PT for maintaining the sperm
      integrity.

PMID- 28752592
TI  - Atomic Force Microscopy as a Tool to Assess the Specificity of Targeted
      Nanoparticles in Biological Models of High Complexity.
AB  - The ability to design nanoparticle delivery systems capable of selectively target
      their payloads to specific cell populations is still a major caveat in
      nanomedicine. One of the main hurdles is the fact that each nanoparticle
      formulation needs to be precisely tuned to match the specificities of the target
      cell and route of administration. In this work, molecular recognition force
      spectroscopy (MRFS) is presented as a tool to evaluate the specificity of neuron
      targeted trimethyl chitosan nanoparticles to neuronal cell populations in
      biological samples of different complexity. The use of atomic force microscopy
      tips functionalized with targeted or non-targeted nanoparticles made it possible
      to assess the specific interaction of each formulation with determined cell
      surface receptors in a precise fashion. More importantly, the combination of MRFS
      with fluorescent microscopy allowed to probe the nanoparticles vectoring capacity
      in models of high complexity, such as primary mixed cultures, as well as specific
      subcellular regions in histological tissues. Overall, this work contributes for
      the establishment of MRFS as a powerful alternative technique to animal testing
      in vector design and opens new avenues for the development of advanced targeted
      nanomedicines.

PMID- 28752593
TI  - Dynamics of Templated Assembly of Nanoparticle Filaments within Nanochannels.
AB  - Nanoparticles (NPs) can self-assemble into complex, organized superstructures on
      patterned surfaces through fluid-mediated interactions. However, the detailed
      mechanisms for such NP assemblies are largely unknown. Here, using in situ
      transmission electron microscopy, the stepwise self-assembly dynamics of
      hydrophobic gold NPs into long filaments formed on the surfaces of water-filled
      patterned nanochannel templates is observed. First, the formation of a meniscus
      between the nanochannel walls, during the slow drying of water, causes
      accumulation of the NPs in the middle of the nanochannels. Second, owing to the
      strong van der Waals attraction between the NP ligands, the NPs condense into
      filaments along the centers of the nanochannels. Filaments with highly
      fluctuating longitudinal NP densities are also observed to fragment into
      separated structures. Understanding the intermediate stages of fluid-mediated NP
      self-assembly on patterned surfaces will have important implications for the
      controlled formation of templated NP assemblies with numerous applications.

PMID- 28752594
TI  - Serum N-glycans outperform CA19-9 in diagnosis of extrahepatic
      cholangiocarcinoma.
AB  - Extensive efforts have been devoted to improve the diagnosis of extrahepatic
      cholangiocarcinoma (ECCA) due to its silent clinical character and lack of
      effective diagnostic biomarkers. Specific alterations in N-glycosylation of
      glycoproteins are considered a key component in cancer progression, which can
      serve as a distinct molecular signature for cancer detection. This study aims to
      find potential serum N-glycan markers for ECCA. In total, 255 serum samples from
      patients with ECCA (n = 106), benign bile tract disease (BBD, n = 60) and healthy
      controls (HC, n = 89) were recruited. Only 2 MUL of serum from individual
      patients was used in this assay where the N-glycome of serum glycoproteins was
      profiled by DNA sequencer-assisted fluorophore-assisted capillary electrophoresis
      (DSA-FACE) technology. Multi-parameter models were constructed by combining the N
      glycans and carbohydrate antigen 19-9 (CA19-9) which is currently used
      clinically. Quantitative analyses showed that among 13 N-glycan structures, the
      bifucosylated triantennary N-glycan (peak10, NA3F2) presented the best diagnostic
      performance for distinguishing ECCA from BBD and HC. Two diagnostic models
      (Glycotest1 and Glycotest2) performed better than single N-glycan or CA19-9.
      Additionally, two N-glycan structures (peak9, NA3Fb; peak12, NA4Fb) were tightly
      related to lymph node metastasis in ECCA patients. In conclusion, sera of ECCA
      showed relatively specific N-glycome profiling patterns. Serum N-glycan markers
      and models are novel, valuable and noninvasive alternatives in ECCA diagnosis and
      progression monitoring.

PMID- 28752595
TI  - Investigating in utero fetal death: outcome of internal medicine consultation.
AB  - AIM: The objectives were to determine the frequency of in utero fetal death
      (IUFD) related to placental disorders and to assess the frequency of
      antiphospholipid antibodies syndrome (APS) among women referred to the internal
      medicine department. METHODOLOGY: A retrospective clinical study conducted in
      Rennes University Hospital, France. From January 2007 to December 2014, 53 women
      who presented an IUFD at 14 weeks or more of gestational age were included. The
      main cause for each IUFD was determined by expert agreement. Primary outcome was
      to analyze the final etiologies diagnosed and the prevalence of IUFD related to
      placental disorders. Secondary outcomes included the frequency of APS among
      patients with IUFD of placental origin and the pathological and clinical features
      associated with APS. RESULTS: IUFD resulted from placental disorders in 36/53
      (68%) patients, and remained unexplained in 11 cases (20.8%). Among the 36
      patients with placental disorders, APS was diagnosed in five (13.9%) cases, and
      four (11.1%) patients were considered as having 'non-criteria' APS. History of
      thrombosis (P = 0.001) and placental infarcts (P = 0.047) were significantly
      associated with APS. CONCLUSION: Placental disorders were the major cause for
      IUFD in patients who were referred to internal medicine specialists. Importantly,
      APS was seldom found in patients with placental disorders. Venous thromboembolism
      history and placental infarcts were both significantly associated with APS.
      Further studies are needed in order to deepen our understanding of the
      physiopathology of placental disorders and its underlying causes among non-APS
      women, and to determine the best treatment regimen for future pregnancies.

PMID- 28752596
TI  - Additional value of the ratio of serum total testosterone to total prostate
      specific antigen in the diagnosis of prostate cancer in a Chinese population.
AB  - We investigated whether serum testosterone and testosterone/prostate-specific
      antigen ratio (T/PSA) might be prostate cancer (PCa) biomarkers. We
      retrospectively reviewed 92 patients with benign prostatic hyperplasia (BPH) and
      164 patients with PCa treated at Zhongshan Hospital, China (April 2012 to
      November 2013). The BPH and PCa groups had similar serum total testosterone
      (median, 15.8 versus 16.3 nmol/L).Compared with the BPH group, the PCa group had
      higher PSA (16.8 versus 5.1 ng/ml) and lower free/total PSA (9.5% versus 19.3%)
      and T/PSA (1.37 versus 4.69) (all p < .001).Patients with PCa and PSA <=20 ng/ml
      had higher testosterone (17.5 versus 12.9 ng/ml; p = .002) and T/PSA (2.24 versus
      0.29; p < .001) than those with PSA >20 ng/ml. Patients with PCa and Gleason
      score <=7 had higher testosterone (18.3 versus 14.1 ng/ml; p = .023) and T/PSA
      (1.93 versus 0.72; p < .001) than those with Gleason score >7. In patients with
      PSA <=20 ng/ml, T/PSA was higher in those with BPH than in those with PCa (4.69
      versus 2.24; p < .001). ROC curve analysis yielded an AUC of 0.712; for the
      optimal cut-off of 4.43, specificity and sensitivity were 52% and 97%
      respectively. T/PSA may improve the accuracy of PCa diagnosis in patients with a
      PSA level <=20 ng/ml.

PMID- 28752597
TI  - Comparative landscape genetics of pond-breeding amphibians in Mediterranean
      temporal wetlands: The positive role of structural heterogeneity in promoting
      gene flow.
AB  - Comparative landscape genetics studies can provide key information to implement
      cost-effective conservation measures favouring a broad set of taxa. These studies
      are scarce, particularly in Mediterranean areas, which include diverse but
      threatened biological communities. Here, we focus on Mediterranean wetlands in
      central Iberia and perform a multi-level, comparative study of two endemic pond
      breeding amphibians, a salamander (Pleurodeles waltl) and a toad (Pelobates
      cultripes). We genotyped 411 salamanders from 20 populations and 306 toads from
      16 populations at 18 and 16 microsatellite loci, respectively, and identified
      major factors associated with population connectivity through the analysis of
      three sets of variables potentially affecting gene flow at increasingly finer
      levels of spatial resolution. Topographic, land use/cover, and remotely sensed
      vegetation/moisture indices were used to derive optimized resistance surfaces for
      the two species. We found contrasting patterns of genetic structure, with
      stronger, finer scale genetic differentiation in Pleurodeles waltl, and notable
      differences in the role of fine-scale patterns of heterogeneity in vegetation
      cover and water content in shaping patterns of regional genetic structure in the
      two species. Overall, our results suggest a positive role of structural
      heterogeneity in population connectivity in pond-breeding amphibians, with
      habitat patches of Mediterranean scrubland and open oak woodlands ("dehesas")
      facilitating gene flow. Our study highlights the usefulness of remotely sensed
      continuous variables of land cover, vegetation and water content (e.g., NDVI,
      NDMI) in conservation-oriented studies aimed at identifying major drivers of
      population connectivity.

PMID- 28752599
TI  - On the independent gene trees assumption in phylogenomic studies.
AB  - Multilocus coalescent methods for inferring species trees or historical
      demographic parameters typically require the assumption that gene trees for
      sampled SNPs or DNA sequence loci are conditionally independent given their
      species tree. In practice, researchers have used different criteria to delimit
      "independent loci." One criterion identifies sampled loci as being independent of
      each other if they undergo Mendelian independent assortment (IA criterion).
      O'Neill et al. (2013, Molecular Ecology, 22, 111-129) used this approach in their
      phylogeographic study of North American tiger salamander species complex. In two
      other studies, researchers developed a pair of related methods that employ an
      independent genealogies criterion (IG criterion), which considers the effects of
      population-level recombination on correlations between the gene trees of
      intrachromosomal loci. Here, I explain these three methods, illustrate their use
      with example data, and evaluate their efficacies. I show that the IA approach is
      more conservative, is simpler to use and requires fewer assumptions than the IG
      approaches. However, IG approaches can identify much larger numbers of
      independent loci than the IA method, which, in turn, allows researchers to obtain
      more precise and accurate estimates of species trees and historical demographic
      parameters. A disadvantage of the IG methods is that they require an estimate of
      the population recombination rate. Despite their drawbacks, IA and IG approaches
      provide molecular ecologists with promising a priori methods for selecting SNPs
      or DNA sequence loci that likely meet the independence assumption in coalescent
      based phylogenomic studies.

PMID- 28752598
TI  - Supercritical Fluid Technology: An Emphasis on Drug Delivery and Related
      Biomedical Applications.
AB  - During the past few decades, supercritical fluid (SCF) has emerged as an
      effective alternative for many traditional pharmaceutical manufacturing
      processes. Operating active pharmaceutical ingredients (APIs) alone or in
      combination with various biodegradable polymeric carriers in high-pressure
      conditions provides enhanced features with respect to their physical properties
      such as bioavailability enhancement, is of relevance to the application of SCF in
      the pharmaceutical industry. Herein, recent advances in drug delivery systems
      manufactured using the SCF technology are reviewed. We provide a brief
      description of the history, principle, and various preparation methods involved
      in the SCF technology. Next, we aim to give a brief overview, which provides an
      emphasis and discussion of recent reports using supercritical carbon dioxide (SC
      CO2 ) for fabrication of polymeric carriers, for applications in areas related to
      drug delivery, tissue engineering, bio-imaging, and other biomedical
      applications. We finally summarize with perspectives.

PMID- 28752602
TI  - Alterations in the steroid biosynthetic pathways in the human prefrontal cortex
      in mood disorders: A post-mortem study.
AB  - Altered levels of steroids have been reported in the brain, cerebral spinal fluid
      and plasma of patients with mood disorders. Neuroimaging studies have reported
      both functional and structural alterations in mood disorders, for instance in the
      anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC). In
      order to determine whether the endogenous production of steroids is altered in
      the ACC and DLPFC of patients with major depressive disorder (MDD) or bipolar
      disorder (BPD), quantitative real-time PCR was performed to detect mRNA
      expression level of key enzymes in the steroid biosynthetic pathways. In MDD, a
      significant decrease in mRNA level of cytochrome P450 17A1 (CYP17A1, synthesizing
      C19 ketosteroids) in the ACC and a significant increase in mRNA levels of
      hydroxysteroid sulfotransferase 2A1 [SULT2A1, catalyzing the sulfate conjugation
      of dehydroepiandrosterone (DHEA)] were observed in the DLPFC, suggesting
      alterations in DHEA and its sulfate metabolite DHEAS levels. Decreased intensity
      and distribution of CYP17A1 immunohistochemical staining was found in the ACC of
      MDD patients. Interestingly, there was a significant positive correlation between
      the mRNA levels of CYP17A1 and tyrosine-related kinase B (TrkB) full length
      isoform. In a unique post-mortem human brain slice culture paradigm, BDNF mRNA
      expression was found to be significantly increased following incubation with
      DHEA. Together, these data indicate a close relationship between DHEA and BDNF
      TrkB pathways in depression. Furthermore, in the DLPFC, higher mRNA levels of
      11beta-hydroxysteroid dehydrogenase-1 (HSD11B1, reducing cortisone to the active
      hormone cortisol) and steroidogenic acute regulatory protein (STAR, facilitating
      the shuttle of cholesterol through the intermembrane space) were found in the MDD
      patients and BPD patients, respectively. In conclusion, this study suggests the
      presence of a disturbance in the endogenous synthesis of DHEA and DHEAS in mood
      disorders, which has a close relationship with BDNF-TrkB signaling.

PMID- 28752601
TI  - Progression of hepatitis C in the haemophiliac population in Ireland, after 30
      years of infection in the pre-DAA treatment era.
AB  - INTRODUCTION: Prior to the introduction of viral inactivation of factor
      concentrates and screening of blood, 225 people with haemophilia became infected
      with hepatitis C (HCV) in Ireland. AIM: Our aim was to assess liver disease
      progression and mortality in this population after 30 years of infection.
      METHODS: Demographic and clinical data were collected from medical records in
      five hepatology units and one infectious disease unit retrospectively in 2005,
      and on four subsequent occasions. RESULTS: The participation rate was 73%
      (165/225). Eighty three percent of patients, who had been tested for RNA (n =
      106/128), developed chronic HCV infection. Thirty four percent were co-infected
      with HIV. All-cause mortality, after approximately 30 years of infection with
      chronic HCV, was 44% in HIV positive patients and 29% in HIV negative patients.
      Liver-related mortality was 12.5% and did not vary significantly by HIV status.
      Thirty seven percent of patients had developed advanced liver disease, including
      20% with cirrhosis and 9% with hepatocellular carcinoma. In the pre-interferon
      free direct acting antivirals era, 57% (n = 60/106) of patients were treated for
      HCV, 65% of whom achieved a sustained virological response. Successfully treated
      patients had few adverse liver outcomes. CONCLUSION: After 30 years of infection,
      40% of the patients who had evidence of chronic HCV had developed advanced liver
      disease, such as cirrhosis and HCC, or had died from liver-related causes. This
      proportion is high relative to similar international cohorts despite good anti
      HCV treatment uptake and responses.

PMID- 28752600
TI  - Getting Drugs Across Biological Barriers.
AB  - The delivery of drugs to a target site frequently involves crossing biological
      barriers. The degree and nature of the impediment to flux, as well as the
      potential approaches to overcoming it, depend on the tissue, the drug, and
      numerous other factors. Here an overview of approaches that have been taken to
      crossing biological barriers is presented, with special attention to transdermal
      drug delivery. Technology and knowledge pertaining to addressing these issues in
      a variety of organs could have a significant clinical impact.

PMID- 28752603
TI  - Carbon input by roots into the soil: Quantification of rhizodeposition from root
      to ecosystem scale.
AB  - Despite its fundamental role for carbon (C) and nutrient cycling, rhizodeposition
      remains 'the hidden half of the hidden half': it is highly dynamic and
      rhizodeposits are rapidly incorporated into microorganisms, soil organic matter,
      and decomposed to CO2 . Therefore, rhizodeposition is rarely quantified and
      remains the most uncertain part of the soil C cycle and of C fluxes in
      terrestrial ecosystems. This review synthesizes and generalizes the literature on
      C inputs by rhizodeposition under crops and grasslands (281 data sets). The
      allocation dynamics of assimilated C (after 13 C-CO2 or 14 C-CO2 labeling of
      plants) were quantified within shoots, shoot respiration, roots, net
      rhizodeposition (i.e., C remaining in soil for longer periods), root-derived CO2
      , and microorganisms. Partitioning of C pools and fluxes were used to extrapolate
      belowground C inputs via rhizodeposition to ecosystem level. Allocation from
      shoots to roots reaches a maximum within the first day after C assimilation.
      Annual crops retained more C (45% of assimilated 13 C or 14 C) in shoots than
      grasses (34%), mainly perennials, and allocated 1.5 times less C belowground. For
      crops, belowground C allocation was maximal during the first 1-2 months of growth
      and decreased very fast thereafter. For grasses, it peaked after 2-4 months and
      remained very high within the second year causing much longer allocation periods.
      Despite higher belowground C allocation by grasses (33%) than crops (21%), its
      distribution between various belowground pools remains very similar. Hence, the
      total C allocated belowground depends on the plant species, but its further fate
      is species independent. This review demonstrates that C partitioning can be used
      in various approaches, e.g., root sampling, CO2 flux measurements, to assess
      rhizodeposits' pools and fluxes at pot, plot, field and ecosystem scale and so,
      to close the most uncertain gap of the terrestrial C cycle.

PMID- 28752604
TI  - Shaping Antiaromatic pi-Systems by Metalation: Synthesis of a Bowl-Shaped
      Antiaromatic Palladium Norcorrole.
AB  - The synthesis of a bowl-shaped antiaromatic molecule was achieved through the
      deformation of a planar antiaromatic porphyrinic pi-conjugation system by
      insertion of palladium into the small cavity of a metal-free norcorrole. The bowl
      to-bowl inversion dynamics of the antiaromatic Pd-coordinated norcorrole was
      determined by variable-temperature 1 H NMR spectroscopy. The metal-free
      norcorrole was prepared from acid-induced demetalation of a copper norcorrole,
      which was obtained from the intramolecular coupling of a bis(diiododipyrrin)
      copper complex with copper thiophenecarboxylate.

PMID- 28752606
TI  - Successful multi-target therapy including rituximab and mycophenolate mofetil in
      anti-melanoma differentiation-associated gene 5 antibody-positive rapidly
      progressive interstitial lung disease with clinically amyopathic dermatomyositis.

PMID- 28752605
TI  - Peaks of in situ N2 O emissions are influenced by N2 O-producing and reducing
      microbial communities across arable soils.
AB  - Agriculture is the main source of terrestrial N2 O emissions, a potent greenhouse
      gas and the main cause of ozone depletion. The reduction of N2 O into N2 by
      microorganisms carrying the nitrous oxide reductase gene (nosZ) is the only known
      biological process eliminating this greenhouse gas. Recent studies showed that a
      previously unknown clade of N2 O-reducers (nosZII) was related to the potential
      capacity of the soil to act as a N2 O sink. However, little is known about how
      this group responds to different agricultural practices. Here, we investigated
      how N2 O-producers and N2 O-reducers were affected by agricultural practices
      across a range of cropping systems in order to evaluate the consequences for N2 O
      emissions. The abundance of both ammonia-oxidizers and denitrifiers was
      quantified by real-time qPCR, and the diversity of nosZ clades was determined by
      454 pyrosequencing. Denitrification and nitrification potential activities as
      well as in situ N2 O emissions were also assessed. Overall, greatest differences
      in microbial activity, diversity, and abundance were observed between sites
      rather than between agricultural practices at each site. To better understand the
      contribution of abiotic and biotic factors to the in situ N2 O emissions, we
      subdivided more than 59,000 field measurements into fractions from low to high
      rates. We found that the low N2 O emission rates were mainly explained by
      variation in soil properties (up to 59%), while the high rates were explained by
      variation in abundance and diversity of microbial communities (up to 68%).
      Notably, the diversity of the nosZII clade but not of the nosZI clade was
      important to explain the variation of in situ N2 O emissions. Altogether, these
      results lay the foundation for a better understanding of the response of N2 O
      reducing bacteria to agricultural practices and how it may ultimately affect N2 O
      emissions.

PMID- 28752608
TI  - Different solutions to restoring oxygen delivery at altitude.

PMID- 28752607
TI  - Reproducibility of heart rate recovery in patients with intermittent
      claudication.
AB  - BACKGROUND: Postexercise heart rate recovery (HRR) is a non-invasive tool for
      cardiac autonomic function assessment. Reproducibility of HRR has been
      established in healthy subjects; however, no study has evaluated this
      reproducibility in clinical populations who may present autonomic dysfunction.
      Patients with peripheral artery disease and intermittent claudication (IC) often
      present altered cardiac autonomic function and HRR could be an interesting tool
      for evaluating autonomic responses to interventions in this population.
      Therefore, the reproducibility of HRR should be determined in this specific
      population. OBJECTIVE: To determine the reproducibility of HRR indices in
      patients with IC. METHODS: Nineteen men with IC underwent two repeated maximal
      treadmill tests. Raw HR and relative HRR (difference to exercise peak) indices
      measured at 30, 60, 120, 180, 240 and 300s of recovery were evaluated. The
      presence of systematic bias was assessed by comparing test and retest mean values
      via paired t-test. Reliability was assessed by intraclass correlation coefficient
      (ICC), and agreement by typical error (TE), coefficient of variation (CV) and
      minimal detectable difference (MDD). RESULTS: There were no significant
      differences between the test and retest values of all raw HR and relative HRR
      indices (P >= 0.05), except for HR120s (P = 0.032). All indices exhibited
      excellent reliability (ICC >= 0.78). Raw HR and relative HRR indices showed TEs
      <= 6.4 bpm and MDDs <= 17.8 bpm. In addition, all indices showed CVs <= 13.2%,
      except HRR30s (CV = 45.6%). CONCLUSIONS: The current results demonstrated that
      most HRR indices were highly reproducible with no systematic error, excellent
      reliability and good agreement in patients with IC following maximal graded
      exercise.

PMID- 28752609
TI  - The atrial appendage as a suitable source to generate cardiac-derived adherent
      proliferating cells for regenerative cell-based therapies.
AB  - Cardiac-derived adherent proliferating (CardAP) cells obtained from
      endomyocardial biopsies (EMBs) with known anti-fibrotic and pro-angiogenic
      properties are good candidates for the autologous therapy of end-stage cardiac
      diseases such as dilated cardiomyopathy. However, due to the limited number of
      CardAP cells that can be obtained from EMBs, our aim is to isolate cells with
      similar properties from other regions of the heart with comparable tissue
      architecture. Here, we introduce the atrial appendage as a candidate region.
      Atrial appendage-derived cells were sorted with CD90 microbeads to obtain a
      CD90low cell population, which were subsequently analysed for their surface
      marker and gene expression profiles via flow cytometry and micro array analysis.
      Enzyme-linked immunosorbent assays for vascular endothelial growth factor and
      interleukin-8 as well as tube formation assays were performed to investigate pro
      angiogenic properties. Furthermore, growth kinetic assays were performed to
      estimate the cell numbers needed for cell-based products. Microarray analysis
      revealed the expression of numerous pro-angiogenic genes and strong similarities
      to CardAP cells with which they also share expression levels of defined surface
      antigens, that is, CD29+ , CD44+ , CD45- , CD73+ , CD90low , CD105+ , and CD166+
      . High secretion levels of vascular endothelial growth factor and interleukin-8
      as well as improved properties of vascular structures in vitro could be detected.
      Based on growth parameters, cell dosages for the treatment of more than 250
      patients are possible using one appendage. These results lead to the conclusion
      that isolating cells with regenerative characteristics from atrial appendages is
      feasible and permits further investigations towards allogenic cell-based
      therapies.

PMID- 28752610
TI  - Intrapericardial dermoid cyst presenting with acute coronary syndrome.

PMID- 28752611
TI  - Quality assessment and improvement of "Unsatisfactory" liquid-based
      cervicovaginal papanicolaou smears.
AB  - OBJECTIVES: The quality of cervicovaginal smears determines the success of
      cytology in screening programs for cervical cancer. Bethesda 2014 revisited the
      adequacy criteria for atrophic smears and redefined the squamous cell count in
      the "unsatisfactory" category. In this study, we evaluated the smear quality of
      Thinprep liquid-based cervicovaginal Papanicolaou cytology slides (TPS) that were
      previously deemed unsatisfactory, to determine reasons for such categorization.
      In addition, we attempted to establish the impact of the new adequacy criteria on
      the rate and management of unsatisfactory diagnosis. METHODS: About 234
      unsatisfactory TPS were examined. The reasons for unsatisfactory were noted. The
      number of squamous cells was recounted, as per the new Bethesda criteria, in
      borderline adequacy cases that showed an atrophic pattern. RESULTS: The leading
      cause for unsatisfactory TPS was lubricating gel, followed by blood, as observed
      in older and younger age groups, respectively (Figure 1). Eleven borderline cases
      were reclassified as "satisfactory" using the new Bethesda cell count, with 27%
      above 60 years of age. About 82% of these borderline cases were negative for
      intraepithelial lesion or malignancy on repeat testing. CONCLUSIONS: There was no
      difference of management or change in rate of unsatisfactory when patients above
      60 were reclassified into the satisfactory category using the new Bethesda count.
      However, a larger study is needed to evaluate whether the new recommendation for
      minimum cellularity can be implemented in patients above a certain age cut-off.
      The study highlights the need for improvement in collection practices and
      education of practitioners.

PMID- 28752612
TI  - App-based attention training: Incorporating older adults' feedback to facilitate
      home-based use.
AB  - BACKGROUND: Technology-based attention training programs have demonstrated
      promise in improving cognitive functioning in older adults. AIMS AND OBJECTIVES:
      The purpose of this study was to evaluate the usability and acceptability of a
      modified version of a mobile attention training application. DESIGN: A
      descriptive, mixed-methods design was used to capture older adults' feedback on
      the usability and acceptability of the modified attention training application.
      METHODS: A convenience sample of older adults (n = 12) participated in three
      study visits and a one-week testing period of the modified attention training
      application in their homes. Descriptive statistics were calculated for all
      quantitative data, and an iterative content analysis was used to characterise
      participant responses. RESULTS: On average, participants rated the modified
      attention training application more positively than negatively in terms of
      usability, interest, enjoyment and satisfaction. The qualitative analyses
      revealed positive aspects of using the app including working through challenges,
      perceived benefit and helpfulness of instructions. CONCLUSIONS: The modified
      attention training application was usable by and acceptable to the majority of
      older adults in our sample who had varying degrees of experience with mobile
      technology. Future development should specifically consider personal
      characteristics as well as individual preferences to maximise the potential of
      the modified attention training application. IMPLICATIONS FOR PRACTICE: This
      technology may be helpful for providing memory improvement interventions to older
      persons with cognitive impairment who do not have access to memory clinics.

PMID- 28752613
TI  - Sleep patterns among patients with chronic fatigue: A polysomnography-based
      study.
AB  - OBJECTIVES: The purpose of this study was to detect treatable sleep disorders
      among patients complaining of chronic fatigue by using sleep questionnaires and
      polysomnography. METHODS: Patients were referred to hospital for investigations
      and rehabilitation because of a suspected diagnosis of myalgic
      encephalomyelitis/chronic fatigue syndrome (ME/CFS). The criteria for further
      referral to full-night polysomnography (PSG) were symptoms of excessive daytime
      sleepiness and/or tiredness in the questionnaires. RESULTS: Of a total of 381
      patients, 78 (20.5%) patients underwent PSG: 66 women and 12 men, mean age 48.6
      years, standard deviation +/-9.9 years. On the basis of the PSG, 31 (40.3%)
      patients were diagnosed with obstructive sleep apnoea, 7 (8.9%) patients with
      periodic limb movement disorder, 32 (41.0%) patients with restless legs syndrome
      and 54 (69.3%) patients had one or more other sleep disorder. All patients were
      grouped into those who fulfilled the diagnostic criteria for ME/CFS (n = 55,
      70.5%) and those who did not (n = 23, 29.5%). The latter group had significantly
      higher respiratory (P = .01) and total arousal (P = .009) indexes and a higher
      oxygen desaturation index (P = .009). CONCLUSIONS: More than half of these
      chronic fatigue patients, who also have excessive daytime sleepiness and/or
      tiredness, were diagnosed with sleep disorders such as obstructive sleep apnoea,
      periodic limb movement disorder and/or restless legs syndrome. Patients with such
      complaints should undergo polysomnography, fill in questionnaires and be offered
      treatment for sleep disorders before the diagnose ME/CFS is set.

PMID- 28752614
TI  - Relationship of body fat and body mass index in young Pacific Islanders: a cross
      sectional study in European, Melanesian and Polynesian groups.
AB  - BACKGROUND: Body mass index is the most often used indicator of obesity but does
      not distinguish between lean and fat mass. Adiposity at the same body mass index
      differs across ethnic groups. OBJECTIVES: The twofold aim of this study was to
      determine whether body mass index (BMI)-based references are correlated with body
      fat percentage (%BF) in a pluri-ethnic population of Pacific Islanders and to
      assess the diagnostic accuracy of these references by using the percentage of
      body fat as the gold standard. METHODS: Height and weight were obtained, and
      triceps and subscapular skinfold thicknesses were measured in a sample of 796
      adolescents (11-16 years) from the three main ethnic groups in New Caledonia:
      Melanesian, European and Polynesian. %BF was derived from the Slaughter
      equations, and BMI z score was calculated by using various international and
      national references. RESULTS: Melanesian teens had lower %BF compared with their
      European counterparts for the same BMI z score. Whatever the BMI-based reference
      used to detect overfatness (%BF >25% for boys and >30% for girls), sensitivity
      was higher in Melanesian adolescents, while specificity was higher in their
      European counterparts. Diagnostic accuracy was better in Melanesian compared with
      European adolescents. CONCLUSIONS: This study shows that Melanesian adolescents
      have lower %BF than their European counterparts for the same BMI z score.
      Therefore, the diagnostic accuracy of BMI to detect overfatness is related to
      ethnicity. Whatever the BMI-based reference, sensitivity was higher in the
      Melanesian group, while specificity was higher in the European group.

PMID- 28752615
TI  - Systematic literature review to identify methods for treating and preventing
      bacterial skin infections in Indigenous children.
AB  - BACKGROUND/OBJECTIVES: Bacterial skin infections in Indigenous children in
      Australia frequently lead them to access primary health care. This systematic
      review aims to identify and analyse available studies describing the treatment
      and prevention of bacterial skin infections in Indigenous children. METHODS:
      Electronic databases including Scopus, MEDLINE, CINAHL, ProQuest, Informit and
      Google Scholar were searched. Studies in English published between August 1994
      and September 2016, with the subject of bacterial skin infections involving
      Indigenous children and conducted in Australia, New Zealand, the USA or Canada
      were selected. RESULTS: Initially 1474 articles were identified. After the
      application of inclusion and exclusion criteria, 10 articles remained. Strategies
      for the treatment and prevention of bacterial skin infections included the
      management of active infections and lesions, improving environmental and personal
      hygiene, the installation of swimming pools and screening and treatment.
      CONCLUSION: There is a need for more, rigorous, large-scale studies to develop
      evidence for appropriate, culturally acceptable methods to prevent and manage
      bacterial skin infections in Indigenous children in Australia. The problem is
      complex with multiple determinants. Until underlying socioeconomic conditions are
      addressed skin infections will continue to be a burden to communities.

PMID- 28752616
TI  - Study on testicular response to prolong artemisinin-based combination therapy
      treatments in guinea pigs.
AB  - Artemisinin-based combination therapies (ACTs) are first-line agents in malaria
      chemotherapy, but often abused in malaria endemic countries including Nigeria.
      This study investigated the effects of prolong treatment of artesunate
      amodiaquine (ATS-Amod), artesunate-sulfadoxine-pyrimethamine (ATS-SP) and
      artemether-lumefantrine (ATM-Lum) on testicular indices in guinea pigs. Sixty
      five pigs were grouped into 13 (n = 5 per group). Six groups were given standard
      or double therapeutic dose equivalents of ATS-Amod, ATS-SP or ATM-Lum daily for
      14 day and sacrificed 24 hr after treatments. Six other groups (recovery groups)
      received similar drug treatments but allowed to recover for 14 day before
      sacrificed. Control group received distilled water. ATS-Amod, ATS-SP and ATM-Lum,
      respectively, decreased (p < .01) sperm count (17.7%, 37.7% and 33.8%), motility
      (48.6%, 50% and 51.4%), viability (32.7%, 43.7% and 35.9%) and morphology
      (123.5%, 0% and 0%), compared to control. These effects were reversed in recovery
      animals. Also, they decreased (p < .01) luteinising hormone and testosterone
      serum levels, without affecting follicle-stimulating hormone. Testicular
      malondialdehyde level was elevated, and glutathione was decreased, while catalase
      and superoxide dismutase enzymes were unaffected by the drugs. The alterations
      were all reversed in recovery animals. The study reveals that prolong
      administration of ACTs results in reversible alteration of sperm parameters and
      reduction of testosterone which is partly attributable to oxidative stress.

PMID- 28752617
TI  - High body mass index is a predictor of left ventricular reverse remodelling in
      heart failure with reduced ejection fraction.
AB  - AIMS: Structural and functional left ventricular alterations can occur in heart
      failure (HF), referred to as left ventricular reverse remodelling (LVRR). This
      study aimed to define novel predictors of LVRR besides well-known effects of
      medical and device therapy. METHODS AND RESULTS: From echographic database, we
      included 295 patients with both left ventricular ejection fraction (LVEF) <=45%
      and indexed left ventricular end-diastolic diameter >=33 mm/m2 and who had at
      least two echocardiographic exams with a delay between 3 and 12 months. LVRR was
      defined as the combination of (i) normalization of LVEF (LVEF >=50%) or increase
      in LVEF >=10% and (ii) a decrease in indexed left ventricular end-diastolic
      diameter >=10%. Clinical follow-up was also obtained. LVRR occurred in 53 (18%)
      patients. Patients in the LVRR group were more likely to present with de novo HF
      (75% vs. 42%), had lower LVEF and left ventricular end-diastolic volumes at index
      examination, yet a higher body mass index (BMI) than non-LVRR patients. Obesity
      was observed in 25% of LVRR patients vs. 14% in others. In multivariate analyses,
      BMI (per each 1 kg/m2 increase) emerged as a predictor of LVRR: odds ratio 1.10
      (95% confidence interval 1.02-1.19) after adjustment to other predictors of LVRR.
      During a mean follow-up of 37 months, 32% of patients had a major adverse cardiac
      event; de novo HF, age, and LVEF were associated with major adverse cardiac
      event. CONCLUSIONS: We identified significant relationship between high BMI and
      LVRR. This intriguing novel finding deserves further study.

PMID- 28752618
TI  - Cell size control - a mechanism for maintaining fitness and function.
AB  - The maintenance of cell size homeostasis has been studied for years in different
      cellular systems. With the focus on 'what regulates cell size', the question 'why
      cell size needs to be maintained' has been largely overlooked. Recent evidence
      indicates that animal cells exhibit nonlinear cell size dependent growth rates
      and mitochondrial metabolism, which are maximal in intermediate sized cells
      within each cell population. Increases in intracellular distances and changes in
      the relative cell surface area impose biophysical limitations on cells, which can
      explain why growth and metabolic rates are maximal in a specific cell size range.
      Consistently, aberrant increases in cell size, for example through polyploidy,
      are typically disadvantageous to cellular metabolism, fitness and functionality.
      Accordingly, cellular hypertrophy can potentially predispose to or worsen
      metabolic diseases. We propose that cell size control may have emerged as a
      guardian of cellular fitness and metabolic activity.

PMID- 28752619
TI  - Spectrum and immunophenotyping of 653 patients with B-cell chronic
      lymphoproliferative disorders in China: A single-centre analysis.
AB  - The incidence of B-cell chronic lymphoproliferative disorders (B-CLPDs) is
      significantly lower in China than that in western countries. There have been
      studies involving small cohorts with conflicting results regarding the spectrum
      of B-CLPDs in China, and the types and immunophenotyping of B-CLPDs in China
      remain largely unexplored. We conducted a retrospective analysis of 653 cases of
      B-CLPDs seen in our centre from 2011 to 2015. Four-colour flow cytometry was used
      to determine the expression of each immunological marker, and the diagnostic
      values of the immunological markers were also investigated. Chronic lymphocytic
      leukaemia (CLL) was the most common type of B-CLPD, which was consistent with
      that in west countries. However, the proportions of CLL (55.9%), follicular
      lymphoma (2.6%), and hairy cell leukaemia (0.2%) were lower, while the proportion
      of lymphoplasmacytic lymphoma/WaldenstrOm macroglobulinaemia (5.4%) was higher in
      China, as compared with western countries. With respect to immunophenotypic
      characteristics, CD23 (31.7%) was more frequently expressed in mantle cell
      lymphoma (MCL) in our cohort than that in western countries. Immunophenotyping
      was useful in differentiating MCL from CLL or B-cell prolymphocytic leukaemia and
      lymphoplasmacytic lymphoma/WaldenstrOm macroglobulinaemia from splenic marginal
      zone lymphoma. CD200 was of better diagnostic performance (accuracy: 94.6%) in
      differentiating CLL from MCL compared with CD23 (accuracy: 93.3%). Some cases of
      B-CPLDs, however, had no definite diagnoses, which were diagnosed as CD5+ B-CPLDs
      unclassified (7.7%) and CD5- B-CPLDs unclassified (15.8%). This is the largest
      study that systematically explores the spectrum and immunophenotyping of B-CLPDs
      in Asia, confirming that spectrum of B-CLPDs in China was different from that in
      western countries. The immunophenotypic features of B-CLPDs were similar between
      China and western countries, although a few disparities exist. Cases with no
      definite diagnoses warrant further studies in the future.

PMID- 28752620
TI  - Population-based incidence of diabetic ketoacidosis in type 2 diabetes: medical
      claims data analysis in Japan.
AB  - PURPOSE: Determination of the incidence rate of diabetic ketoacidosis (DKA) in
      type 2 diabetes mellitus (T2DM) is urgent, in response to the safety issue with
      use of the glucose lowering drugs, sodium-glucose cotransporter-2 inhibitors, and
      DKA. METHODS: We extracted data of adult patients with T2DM from a medical claims
      database in Japan, which included 1 million individuals. The study period was
      2005-2013, before the era of sodium-glucose cotransporter-2 inhibitors. The
      inclusion criteria were patients with a diagnosis of T2DM who had at least 1
      prescription for a glucose-lowering drug. We further examined the number of DKA
      related admissions and medication use prior to admission. Calculation of DKA
      incidence was on a patient-years basis, with 95% confidence interval using a
      Poisson distribution. RESULTS: Of 36,674 adult patients with T2DM, we identified
      74 cases admitted for DKA, with an estimated DKA incidence of 0.48/1000 (95%
      confidence interval, 0.38-0.60/1000) patient-years. Of these 74 cases,
      approximately two-thirds of patients had no past or recent history of glucose
      lowering drug use before admission for DKA. CONCLUSIONS: This study estimated
      that the incidence of DKA was 0.48/1000 patient-years in Japan, similar to
      previous studies. We also found that underuse of glucose-lowering medication was
      common among patients hospitalized for DKA. KEY POINTS The population-based
      incidence of DKA in T2DM is largely unknown. In Japan, the estimated DKA
      incidence was 0.48/1000 (95% CI, 0.38-0.60/1000) patient-years. Drug-induced DKA
      is an emerging research area, and our results can be applied to evaluating the
      risk of DKA.

PMID- 28752621
TI  - Anterolateral papillary muscle rupture in Staphylococcus aureus endocarditis due
      to direct bacterial invasion of papillary muscle.
AB  - Rupture of papillary muscles due to infective endocarditis is a very rare event.
      We report a case of anterolateral papillary muscle rupture caused by
      Staphylococcus aureus endocarditis, due to direct bacterial invasion of the
      papillary muscle, resulting in severe mitral regurgitation.

PMID- 28752622
TI  - Response to nitrogen addition reveals metabolic and ecological strategies of soil
      bacteria.
AB  - The nitrogen (N) cycle represents one of the most well-studied systems, yet the
      taxonomic diversity of the organisms that contribute to it is mostly unknown, or
      linked to poorly characterized microbial groups. While new information has
      allowed functional groups to be refined, they still rely on a priori knowledge of
      enzymes involved and the assumption of functional conservation, with little
      connection to the role the transformations, plays for specific organisms. Here,
      we use soil microcosms to test the impact of N deposition on prokaryotic
      communities. By combining chemical, genomic and transcriptomic analysis, we are
      able to identify and link changes in community structure to specific organisms
      catalysing given chemical reactions. Urea deposition led to a decrease in
      prokaryotic richness, and a shift in community composition. This was driven by
      replacement of stable native populations, which utilize energy from N-linked
      redox reactions for physiological maintenance, with fast responding populations
      that use this energy for growth. This model can be used to predict response to N
      disturbances and allows us to identify putative life strategies of different
      functional and taxonomic groups, thus providing insights into how they persist in
      ecosystems by niche differentiation.

PMID- 28752623
TI  - Summer and winter drought drive the initiation and spread of spruce beetle
      outbreak.
AB  - This study used Landsat-based detection of spruce beetle (Dendroctonus
      rufipennis) outbreak over the years 2000-2014 across the Southern Rocky Mountain
      Ecoregion to examine the spatiotemporal patterns of outbreak and assess the
      influence of temperature, drought, forest characteristics, and previous spruce
      beetle activity on outbreak development. During the 1999-2013 period, time series
      of spruce beetle activity were highly spatially correlated (r > 0.5) at distances
      <5 km, but remained weakly correlated (r = 0.08) at distances >400 km.
      Furthermore, cluster analysis on time series of outbreak activity revealed the
      outbreak developed at multiple incipient locations and spread to unaffected
      forest, highlighting the importance of both local-scale dispersal and regional
      scale drivers in synchronizing spruce beetle outbreak. Spatial overlay analysis
      and Random Forest modeling of outbreak development show that outbreaks initiate
      in areas characterized by summer, winter, and multi-year drought and that
      outbreak spread is strongly linked to the proximity and extent of nearby
      outbreak, but remains associated with drought. Notably, we find that spruce
      beetle outbreak is associated with low peak snow water equivalent, not just
      summer drought. As such, future alterations to both winter and summer
      precipitation regimes are likely to drive important changes in subalpine forests.

PMID- 28752624
TI  - Paired motor cortex and cervical epidural electrical stimulation timed to
      converge in the spinal cord promotes lasting increases in motor responses.
AB  - KEY POINTS: Pairing motor cortex stimulation and spinal cord epidural stimulation
      produced large augmentation in motor cortex evoked potentials if they were timed
      to converge in the spinal cord. The modulation of cortical evoked potentials by
      spinal cord stimulation was largest when the spinal electrodes were placed over
      the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord
      stimulation caused lasting increases in evoked potentials from both sites, but
      only if the time between the stimuli was optimal. Both immediate and lasting
      effects of paired stimulation are likely mediated by convergence of descending
      motor circuits and large diameter afferents onto common interneurons in the
      cervical spinal cord. ABSTRACT: Convergent activity in neural circuits can
      generate changes at their intersection. The rules of paired electrical
      stimulation are best understood for protocols that stimulate input circuits and
      their targets. We took a different approach by targeting the interaction of
      descending motor pathways and large diameter afferents in the spinal cord. We
      hypothesized that pairing stimulation of motor cortex and cervical spinal cord
      would strengthen motor responses through their convergence. We placed epidural
      electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor
      evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex
      were robustly augmented with spinal epidural stimulation delivered at an
      intensity below the threshold for provoking an MEP. Augmentation was critically
      dependent on the timing and position of spinal stimulation. When the spinal
      stimulation was timed to coincide with the descending volley from motor cortex
      stimulation, MEPs were more than doubled. We then tested the effect of repeated
      pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong
      augmentation of cortical MEPs and spinal excitability that lasted up to an hour
      after just 5 min of pairing. Additional physiology experiments support the
      hypothesis that paired stimulation is mediated by convergence of descending motor
      circuits and large diameter afferents in the spinal cord. The large effect size
      of this protocol and the conservation of the circuits being manipulated between
      rats and humans makes it worth pursuing for recovery of sensorimotor function
      after injury to the central nervous system.

PMID- 28752625
TI  - Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and
      Astragaloside IV via Down-Regulating Connexin 43.
AB  - Paeoniflorin (PF) and astragaloside IV (AS-IV) have protective effects on
      cerebral ischemia. We aimed to test the effects of combined use of PF and AS-IV
      on ischemic brain edema and investigate whether the effects were dependent on
      connexin43 (Cx43). We detected the expression of Cx43 induced by PF and AS-IV
      after cerebral ischemia. We also examined the effects of combined use of PF and
      AS-IV on ischemic edema and further investigated the related pathways. We
      demonstrated PF and AS-IV decreased Cx43 and aquaporin4 (AQP4) associating with
      reduction of brain edema by dry-wet weight and brain-specific gravity methods
      after cerebral ischemia. Administration of PF and AS-IV displayed a further
      attenuation of brain edema with lower Cx43 levels. Meanwhile, Cx43 blockade
      inhibited AQP4 down-regulation by the two drugs. Moreover, phosphorylation of C
      Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)
      were increased by PF and AS-IV, respectively. The effects of PF and AS-IV to down
      regulate Cx43 were suppressed by JNK and ERK inhibitors, respectively. Our data
      indicate that PF and AS-IV alleviate ischemic brain edema, which has close
      relation to Cx43 down-regulation causing decrease of AQP4 via JNK and ERK
      pathways activation, respectively. Combined administration elicits synergistic
      effects on brain edema reduction. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28752626
TI  - Stand dynamics modulate water cycling and mortality risk in droughted tropical
      forest.
AB  - Transpiration from the Amazon rainforest generates an essential water source at a
      global and local scale. However, changes in rainforest function with climate
      change can disrupt this process, causing significant reductions in precipitation
      across Amazonia, and potentially at a global scale. We report the only study of
      forest transpiration following a long-term (>10 year) experimental drought
      treatment in Amazonian forest. After 15 years of receiving half the normal
      rainfall, drought-related tree mortality caused total forest transpiration to
      decrease by 30%. However, the surviving droughted trees maintained or increased
      transpiration because of reduced competition for water and increased light
      availability, which is consistent with increased growth rates. Consequently, the
      amount of water supplied as rainfall reaching the soil and directly recycled as
      transpiration increased to 100%. This value was 25% greater than for adjacent
      nondroughted forest. If these drought conditions were accompanied by a modest
      increase in temperature (e.g., 1.5 degrees C), water demand would exceed supply,
      making the forest more prone to increased tree mortality.

PMID- 28752627
TI  - Vector competence of northern and southern European Culex pipiens pipiens
      mosquitoes for West Nile virus across a gradient of temperatures.
AB  - In Europe, West Nile virus (WNV) outbreaks have been limited to southern and
      central European countries. However, competent mosquito vectors and susceptible
      bird hosts are present in northern Europe. Differences in temperature and vector
      competence of mosquito populations may explain the absence of WNV outbreaks in
      northern Europe. The aim of the present study was to directly compare vector
      competence of northern and southern European Culex pipiens (Cx. p.) pipiens
      mosquitoes for WNV across a gradient of temperatures. WNV infection and
      transmission rates were determined for two Cx. p. pipiens populations originating
      from The Netherlands and Italy, respectively. Mosquitoes were orally exposed by
      providing an infectious bloodmeal, or by injecting WNV (lineage 2) in the thorax,
      followed by 14-day incubation at 18, 23, or 28  degrees C. No differences in
      infection or transmission rates were found between the Cx. p. pipiens populations
      with both infection methods, but WNV transmission rates were significantly higher
      at temperatures above 18  degrees C. The absence of WNV outbreaks in northern
      Europe cannot be explained by differences in vector competence between Cx. p.
      pipiens populations originating from northern and southern Europe. This study
      suggests that low temperature is a key limiting factor for WNV transmission.

PMID- 28752628
TI  - Intranasal delivery of dexamethasone efficiently controls LPS-induced murine
      neuroinflammation.
AB  - Neuroinflammation is the hallmark of several infectious and neurodegenerative
      diseases. Synthetic glucocorticoids (GCs) are the first-line immunosuppressive
      drugs used for controlling neuroinflammation. A delayed diffusion of GCs
      molecules and the high systemic doses required for brain-specific targeting lead
      to severe undesirable effects, particularly when lifelong treatment is required.
      Therefore, there is an urgent need for improving this current therapeutic
      approach. The intranasal (i.n.) route is being employed increasingly for drug
      delivery to the brain via the olfactory system. In this study, the i.n. route is
      compared to the intravenous (i.v.) administration of GCs with respect to their
      effectiveness in controlling neuroinflammation induced experimentally by systemic
      lipopolysaccharide (LPS) injection. A statistically significant reduction in
      interleukin (IL)-6 levels in the central nervous system (CNS) in the percentage
      of CD45+ /CD11b+ /lymphocyte antigen 6 complex locus G6D [Ly6G+ and in glial
      fibrillary acidic protein (GFAP) immunostaining was observed in mice from the
      i.n.-dexamethasone (DX] group compared to control and i.v.-DX-treated animals. DX
      treatment did not modify the percentage of microglia and perivascular macrophages
      as determined by ionized calcium binding adaptor molecule 1 (Iba1) immunostaining
      of the cortex and hippocampus. The increased accumulation of DX in brain
      microvasculature in DX-i.n.-treated mice compared with controls and DX-IV-treated
      animals may underlie the higher effectiveness in controlling neuroinflammation.
      Altogether, these results indicate that IN-DX administration may offer a more
      efficient alternative than systemic administration to control neuroinflammation
      in different neuropathologies.

PMID- 28752629
TI  - Comparative analyses of basal rate of metabolism in mammals: data selection does
      matter.
AB  - Basal rate of metabolism (BMR) is a physiological parameter that should be
      measured under strictly defined experimental conditions. In comparative analyses
      among mammals BMR is widely used as an index of the intensity of the metabolic
      machinery or as a proxy for energy expenditure. Many databases with BMR values
      for mammals are available, but the criteria used to select metabolic data as BMR
      estimates have often varied and the potential effect of this variability has
      rarely been questioned. We provide a new, expanded BMR database reflecting
      compliance with standard criteria (resting, postabsorptive state; thermal
      neutrality; adult, non-reproductive status for females) and examine potential
      effects of differential selectivity on the results of comparative analyses. The
      database includes 1739 different entries for 817 species of mammals, compiled
      from the original sources. It provides information permitting assessment of the
      validity of each estimate and presents the value closest to a proper BMR for each
      entry. Using different selection criteria, several alternative data sets were
      extracted and used in comparative analyses of (i) the scaling of BMR to body mass
      and (ii) the relationship between brain mass and BMR. It was expected that
      results would be especially dependent on selection criteria with small sample
      sizes and with relatively weak relationships. Phylogenetically informed
      regression (phylogenetic generalized least squares, PGLS) was applied to the
      alternative data sets for several different clades (Mammalia, Eutheria,
      Metatheria, or individual orders). For Mammalia, a 'subsampling procedure' was
      also applied, in which random subsamples of different sample sizes were taken
      from each original data set and successively analysed. In each case, two data
      sets with identical sample size and species, but comprising BMR data with
      different degrees of reliability, were compared. Selection criteria had minor
      effects on scaling equations computed for large clades (Mammalia, Eutheria,
      Metatheria), although less-reliable estimates of BMR were generally about 12-20%
      larger than more-reliable ones. Larger effects were found with more-limited
      clades, such as sciuromorph rodents. For the relationship between BMR and brain
      mass the results of comparative analyses were found to depend strongly on the
      data set used, especially with more-limited, order-level clades. In fact, with
      small sample sizes (e.g. <100) results often appeared erratic. Subsampling
      revealed that sample size has a non-linear effect on the probability of a zero
      slope for a given relationship. Depending on the species included, results could
      differ dramatically, especially with small sample sizes. Overall, our findings
      indicate a need for due diligence when selecting BMR estimates and caution
      regarding results (even if seemingly significant) with small sample sizes.

PMID- 28752630
TI  - Safety and efficacy of percutaneous intramyocardial bone marrow cell injection
      for chronic myocardial ischemia: Long-term results.
AB  - BACKGROUND: Intramyocardial injection of bone marrow cells (BMC) in refractory
      angina patients with chronic myocardial ischemia has shown to be safe and improve
      clinical status during short-term follow-up. However, scarce data are available
      on long-term (>12 months) safety and efficacy. Therefore, the occurrence of
      clinical events and the long-term clinical effects of intramyocardial BMC
      injection were evaluated in patients with chronic myocardial ischemia up to 10
      years after treatment. METHODS AND RESULTS: Patients (n = 100, age 64 +/- 9
      years, male 88%) with chronic myocardial ischemia who underwent intramyocardial
      BMC injection between 2004 and 2010 were evaluated. During yearly outpatient
      clinic visits, the occurrence of clinical events was documented. In addition,
      clinical status was assessed according to the Canadian Cardiovascular Society
      (CCS) score and quality of life was measured using the Seattle Angina
      Questionnaire. These parameters were evaluated at baseline and during the first
      year, followed by cross-sectional long-term follow-up which was performed in 2011
      and 2014. No adverse events considered related to the procedure occurred during
      10 years of follow-up. Observed annual mortality rate and annual myocardial
      infarction rate were 3.8% and 1.9% per year, respectively. When compared to
      baseline, CCS class and quality of life remained significantly better during 5
      year follow-up after BMC treatment (both P < 0.05). CONCLUSIONS: The present long
      term follow-up study shows that intramyocardial BMC injection in patients with
      chronic myocardial ischemia is safe and improves both angina complaints and
      quality of life up to 5 years after BMC treatment.

PMID- 28752631
TI  - What approaches for promoting shared decision-making are used in child mental
      health? A scoping review.
AB  - OBJECTIVE: Whilst the benefits of shared decision-making (SDM) have been promoted
      across different health settings, its implementation is complex, particularly for
      children and young people with mental health difficulties. The aim of this
      scoping review was to identify and describe SDM approaches (tools, techniques,
      and technologies) used in child and youth mental health. METHOD: Electronic
      databases and grey literature were searched. Papers were included if they
      satisfied these criteria: English language; described an SDM approach (tool,
      technique, or technology); included sufficient detail on the SDM approach for
      quality assessment; did not use only a questionnaire to provide feedback on SDM
      or related concepts (e.g., therapeutic alliance) without another SDM approach;
      child or adolescent population (up to 18 years); carers of children or
      adolescents; and mental health setting. Screening and data extraction were
      performed by two co-authors, and each included record was quality assessed
      against a set of essential ingredients of SDM identified by previous studies.
      RESULTS: Of the 8,153 initial results, 22 were eligible for final inclusion.
      These could be grouped into six approaches: therapeutic techniques,
      psychoeducational information, decision aids, action planning or goal setting,
      discussion prompts, and mobilizing patients to engage. The quality of approaches
      identified ranged from one to seven of the nine essential elements of SDM.
      CONCLUSION: Evidence suggests that a range of approaches are being developed to
      support SDM in child and youth mental health. Rigorous research evaluating the
      effectiveness of these approaches is urgently needed, particularly from the
      perspective of children and young people.

PMID- 28752632
TI  - Digest: Does intralocus sexual conflict affect cricket nutrition?

PMID- 28752634
TI  - Characterization of Biomimetic Cofactors According to Stability, Redox
      Potentials, and Enzymatic Conversion by NADH Oxidase from Lactobacillus pentosus.
AB  - Oxidoreductases are attractive biocatalysts that convert achiral substrates into
      products of higher value, but they are also for the most part dependent on
      nicotinamide cofactors. Recently, biomimetic nicotinamide derivatives have
      received attention as less costly alternatives to natural cofactors. However,
      recycling of biomimetics is still challenging because there are only limited
      opportunities. Here, we have characterized various biomimetic cofactors with
      regard to stability and redox potentials to find the best alternative to natural
      cofactors. Further, the cofactor spectrum of NADH oxidase from Lactobacillus
      pentosus (LpNox) could be expanded, and the enzymatic activity was also compared
      to activities with different small-molecule catalysts. As a result, we succeeded
      in identifying several strategies for regeneration of oxidized biomimetics.

PMID- 28752633
TI  - Reproducibility of assessing fecal microbiota in chronic constipation.
AB  - BACKGROUND: While limited data suggest that the fecal microbiota in healthy
      people is stable over time, the intraindividual variability of the fecal
      microbiota in constipated patients is unknown. METHODS: This study evaluated the
      intraindividual reproducibility of fecal microbiota analyzed with 16S rRNA gene
      sequencing in two stool samples collected without and after a laxative,
      respectively, in 25 healthy people and 25 constipated women. Participants
      completed a food record for 3 d before the stool collection. Colonic transit was
      measured with scintigraphy. KEY RESULTS: The constipated patients were older
      (48+/-15 vs 39+/-10 y, P=.02) than healthy participants but had a similar BMI.
      The total daily caloric intake was less (P=.005) in constipated (1265+/-350 kcal)
      than healthy participants (1597+/-402 kcal). Fourteen patients but only two
      controls (P<.005), had delayed colonic transit. For most measures of alpha (eg,
      Observed OTU number, Shannon index) and beta diversity (eg, Bray-Curtis
      dissimilarity, UniFrac, phyla level abundance), the ICCs between two stool
      samples were high, indicating moderate or strong agreement, and similar in
      healthy people and constipated patients. The ICC for the weighted UniFrac
      distance, which is weighted by abundance, was lower than its unweighted
      counterpart, indicating that the unweighted measure is more robust and
      reproducible. CONCLUSIONS AND INFERENCES: The intraindividual reproducibility of
      fecal microbiota in constipated patients is high and comparable to healthy
      participants. For most purposes, evaluating the fecal microbiota in a single
      stool sample should generally suffice in adequately powered studies of healthy
      and constipated patients.

PMID- 28752635
TI  - Hybrid zone formation and contrasting outcomes of secondary contact over
      transects in common toads.
AB  - Much progress in speciation research stems from documenting patterns of
      morphological and genetic variation in hybrid zones. Contrasting patterns of
      marker introgression in different sections of the contact can provide valuable
      insights on the relative importance of various evolutionary mechanisms
      maintaining species differences in the face of hybridization and gene flow and on
      hybrid zone temporal and spatial dynamics. We studied species interactions in the
      common toads Bufo bufo and B. spinosus in France and northwestern Italy using
      morphological and molecular data from the mitochondrial and nuclear genomes in an
      extensive survey, including two independent transects west and east of the Alps.
      At both, we found sharp, coincident and concordant nuclear genetic transitions.
      However, morphological clines were wider or absent and mtDNA introgression was
      asymmetric. We discuss alternative, nonexclusive hypotheses about evolutionary
      processes generating these patterns, including drift, selection, long-distance
      dispersal and spatial shifts in hybrid zone location and structure. The
      distribution of intraspecific mtDNA lineages supports a scenario in which B. bufo
      held a local refugium during the last glacial maximum. Present-day genetic
      profiles are best explained by an advance of B. spinosus from a nearby Iberian
      refugium, largely superseding the local B. bufo population, followed by an
      advance of B. bufo from the Balkans, with prongs north and south of the Alps,
      driving B. spinosus southwards. A pendulum moving hybrid zone, first northwards
      and then southwards, explains the wide areas of introgression at either side of
      the current position of the contact zones.

PMID- 28752636
TI  - Overlap syndrome: juvenile dermatomyositis and perinuclear antineutrophil
      cytoplasmic autoantibody vasculitis, a case report and review of literature.

PMID- 28752637
TI  - Anti-TNF treatment in Crohn's disease and risk of bowel resection-a population
      based cohort study.
AB  - BACKGROUND: TNF inhibitors (TNFi) have been shown to reduce the need for surgery
      in Crohn's disease, but few studies have examined their effect beyond the first
      year of treatment. AIM: To conduct a register-based observational cohort study in
      Sweden 2006-2014 to investigate the risk of bowel resection in bowel surgery
      naive TNFi-treated Crohn's disease patients and whether patients on TNFi >=12
      months are less likely to undergo bowel resection than patients discontinuing
      treatment before 12 months. METHODS: We identified all individuals in Sweden with
      Crohn's disease through the Swedish National Patient Register 1987-2014 and
      evaluated the incidence of bowel resection after first ever dispensation of
      adalimumab or infliximab from 2006 and up to 7 years follow-up. RESULTS: We
      identified 1856 Crohn's disease patients who had received TNFi. Among these
      patients, 90% treatment retention was observed at 6 months after start of TNFi
      and 65% remained on the drug after 12 months. The cumulative rates of surgery in
      Crohn's disease patients exposed to TNFi years 1-7 were 7%, 13%, 17%, 20%, 23%,
      25% and 28%. Rates of bowel resection were similar between patients with TNFi
      survival <12 months and >=12 months respectively (P=.27). No predictors (eg, sex,
      age, extension or duration of disease) for bowel resection were identified.
      CONCLUSIONS: The risk of bowel resection after start of anti-TNF treatment is
      higher in regular health care than in published RCTs. Patients on sustained TNFi
      treatment beyond 12 months have bowel resection rates similar to those who
      discontinue TNFi treatment earlier.

PMID- 28752638
TI  - Wissenschaftspreis 2017: T. Beck / Elected to the Heidelberg Academy of Sciences
      and Frantisek Sorm Memorial Medal: A. Marx / Ruhrpreis fur Kunst und
      Wissenschaft: R. Schlogl / Karl Ziegler Guest Professorship: A. H. Hoveyda.

PMID- 28752639
TI  - Perioperative management of haemophilia B: A critical appraisal of the evidence
      and current practices.
AB  - BACKGROUND: While there is substantial literature addressing the principles of
      general management of haemophilia, literature on perioperative management of
      haemostasis is scarce. OBJECTIVE: The aim of this study was to better understand
      perioperative management among congenital haemophilia B patients (without
      inhibitors) and to gain insights into real-world surgical practices. METHOD: A
      systematic literature review, with an emphasis on haemophilia B, was conducted
      using EMBASE(r) , Medline(r) and the Cochrane Library. Studies from 1974 to June
      2015 were accessed, and 132 studies were eligible for the full-study review. An
      international expert panel with five haematologists and one surgeon reviewed the
      resulting literature and provided further insights. RESULTS: The literature
      review revealed that documented experience in the perioperative management of
      bleeding risk in haemophilia B patients is relatively scarce. Therefore, the
      review was amended to provide a comprehensive overview of the perioperative
      management for haemophilia A and B patients; the expert panel applied a
      particular focus to haemophilia B. Several gaps were identified in the literature
      including the lack of consensus on defining surgery in terms of bleeding risk,
      optimal factor levels during surgery and lack of robust evidence on surgical
      outcomes. The ensuing discussions with the expert panel provided validation of
      some of the results from the systematic literature review and proposed future
      directions for perioperative management. Suggestions included collaboration with
      haemophilia treatment centres (HTCs) to collect real-world data on perioperative
      management, establishing the need for optimal factor level monitoring practice,
      and the appropriate adoption of extended half-life products in clinical settings.

PMID- 28752640
TI  - Early colposcopic reassurance and discharge to routine recall does not increase
      subsequent high-grade referral or treatment rates.
AB  - BACKGROUND: The Jessop Wing Colposcopy Unit identified that between 1st April
      2014 and 31st March 2015 the number of women referred with high-grade dyskaryosis
      and the number of women undergoing treatment increased by 21% and 19%,
      respectively. There was concern that referral and treatment rates were increasing
      because we were now seeing women, previously discharged to routine recall with
      prior low-grade cytology hrHPV positive, re-enter the system for their second
      round of screening. The aim of this study was to assess the reasons for our
      significant increase in referral and treatment rates. METHODS: A retrospective
      cohort study performed between 1st April 2012 and 30th June 2015 at the Jessop
      Wing Colposcopy Unit, Sheffield, UK. RESULTS: During the study period, 1765 women
      underwent large loop excision of the transformation zone (LLETZ), of whom 1517
      were referred with high-grade dyskaryosis. Fifty-six (4%) women undergoing
      treatment; and four untreated high-grade referrals were seen in the previous 3-5
      years with low-grade cytology hrHPV positive and discharged to routine recall.
      There were no cases of invasive disease in the previously discharged groups.
      There was, however, a significantly higher likelihood of a negative LLETZ
      (P=.0066) in those women previously discharged to routine recall, and lower rates
      of CIN2 or worse identified. CONCLUSION: Prior discharge to routine recall does
      not have any major influence on treatment rates or high-grade referrals. The
      finding of no invasive disease; lower rates of CIN2 or worse; and a significantly
      higher likelihood of a negative LLETZ in those women previously discharged to
      routine recall is reassuring and further reinforces the safety of HPV triage
      pathways.

PMID- 28752641
TI  - Influenza virus-like particles harboring H9N2 HA and NA proteins induce a
      protective immune response in chicken.
AB  - BACKGROUND: Avian influenza viruses represent a growing threat of an influenza
      pandemic. The co-circulation of multiple H9N2 genotypes over the past decade has
      been replaced by one predominant genotype-G57 genotype, which displays a changed
      antigenicity and improved adaptability in chickens. Effective H9N2 subtype avian
      influenza virus vaccines for poultry are urgently needed. OBJECTIVE: In this
      study, we constructed H9N2 subtype avian influenza virus-like particle (VLP) and
      evaluated its protective efficacy in specific pathogen-free (SPF) chickens to lay
      the foundation for developing an effective vaccine against influenza viruses.
      METHODS: Expression of influenza proteins in VLPs was confirmed by Western blot,
      hemagglutination inhibition (HI), and neuraminidase inhibition (NI). The
      morphology was observed by electron microscopy. A group of 15 three-week-old SPF
      chickens was divided into three subgroups of five chickens immunized with VLP,
      commercial vaccine, and PBS. Challenge study was performed to evaluate efficacy
      of VLP vaccine. RESULTS AND CONCLUSIONS: The hemagglutinin (HA) and neuraminidase
      (NA) proteins were co-expressed in the infected cells, self-assembled, and were
      released into the culture medium in the form of VLPs of diameter ~80 nm. The VLPs
      exhibited some functional characteristics of a full influenza virus, including
      hemagglutination and neuraminidase activity. In SPF chickens, the VLPs elicited
      serum antibodies specific for H9N2 and induced a higher HI titer (as detected by
      a homologous antigen) than did a commercial H9N2 vaccine
      (A/chicken/Shanghai/F/1998). Viral shedding from VLP vaccine subgroup was reduced
      compared with commercial vaccine subgroup and control subgroup.

PMID- 28752642
TI  - Genome-wide map of Apn1 binding sites under oxidative stress in Saccharomyces
      cerevisiae.
AB  - The DNA is cells is continuously exposed to reactive oxygen species resulting in
      toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage
      occurs primarily through the base excision repair (BER) pathway, the nucleotide
      excision repair (NER) pathway processes some of the same lesions. In addition,
      damage tolerance mechanisms, such as recombination and translesion synthesis,
      enable cells to tolerate oxidative DNA damage, especially when BER and NER
      capacities are exceeded. Thus, disruption of BER alone or disruption of BER and
      NER in Saccharomyces cerevisiae leads to increased mutations as well as large
      scale genomic rearrangements. Previous studies demonstrated that a particular
      region of chromosome II is susceptible to chronic oxidative stress-induced
      chromosomal rearrangements, suggesting the existence of DNA damage and/or DNA
      repair hotspots. Here we investigated the relationship between oxidative damage
      and genomic instability utilizing chromatin immunoprecipitation combined with DNA
      microarray technology to profile DNA repair sites along yeast chromosomes under
      different oxidative stress conditions. We targeted the major yeast AP
      endonuclease Apn1 as a representative BER protein. Our results indicate that Apn1
      target sequences are enriched for cytosine and guanine nucleotides. We predict
      that BER protects these sites in the genome because guanines and cytosines are
      thought to be especially susceptible to oxidative attack, thereby preventing
      large-scale genome destabilization from chronic accumulation of DNA damage.
      Information from our studies should provide insight into how regional deployment
      of oxidative DNA damage management systems along chromosomes protects against
      large-scale rearrangements. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28752643
TI  - Combined deficiency of the Cnr1 and Cnr2 receptors protects against age-related
      bone loss by osteoclast inhibition.
AB  - The endocannabinoid system plays a role in regulating bone mass and bone cell
      activity and inactivation of the type 1 (Cnr1) or type 2 (Cnr2) cannabinoid
      receptors influences peak bone mass and age-related bone loss. As the Cnr1 and
      Cnr2 receptors have limited homology and are activated by different ligands, we
      have evaluated the effects of combined deficiency of Cnr1 and 2 receptors (Cnr1/2
      /- ) on bone development from birth to old age and studied ovariectomy induced
      bone loss in female mice. The Cnr1/2-/- mice had accelerated bone accrual at
      birth when compared with wild type littermates, and by 3 months of age, they had
      higher trabecular bone mass. They were also significantly protected against
      ovariectomy-induced bone loss due to a reduction in osteoclast number. The Cnr1/2
      /- mice had reduced age-related bone loss when compared with wild-type due to a
      reduction in osteoclast number. Although bone formation was reduced and bone
      marrow adiposity increased in Cnr1/2-/- mice, the osteoclast defect outweighed
      the reduction in bone formation causing preservation of bone mass with aging.
      This contrasts with the situation previously reported in mice with inactivation
      of the Cnr1 or Cnr2 receptors individually where aged-related bone loss was
      greater than in wild-type. We conclude that the Cnr1 and Cnr2 receptors have
      overlapping but nonredundant roles in regulating osteoclast and osteoblast
      activities. These observations indicate that combined inhibition of Cnr1 and Cnr2
      receptors may be beneficial in preventing age-related bone loss, whereas blockade
      of individual receptors may be detrimental.

PMID- 28752644
TI  - Hypertension is associated with worse cognitive function and hippocampal
      hypometabolism in Alzheimer's disease.
AB  - BACKGROUND AND PURPOSE: A growing body of evidence suggests that cardiovascular
      disease risk factors including hypertension may be linked to sporadic Alzheimer's
      disease (AD). It is well known that hypertension is associated with
      cerebrovascular disease and vascular dementia on the basis of vascular
      remodeling. However, the mechanisms linking hypertension and AD remain unclear.
      METHODS: We studied 197 patients with AD (86 male; mean age +/- SD: 75.8 +/- 7.4
      years) from the Alzheimer's Disease Neuroimaging Initiative database with (n =
      97) and without (n = 100) hypertension. We explored associations between
      hypertension and clinical, plasma, cerebrospinal fluid and imaging markers of AD
      pathology in order to elucidate the underlying mechanisms that may link AD and
      hypertension. RESULTS: We found that patients with AD with hypertension had worse
      cognitive function (Alzheimer's disease Assessment Scale-cognitive subscale, P =
      0.038) and higher neuropsychiatric symptom burden (Neuropsychiatric Inventory
      Questionnaire, P = 0.016) compared with those without hypertension. Patients with
      AD with hypertension showed reduced glucose hypometabolism in the right (P <
      0.001) and left (P = 0.007) hippocampus. No differences were found in magnetic
      resonance imaging volumetric measurements, [18 F]florbetapir uptakes, plasma and
      cerebrospinal fluid between patients with AD with and without hypertension.
      CONCLUSIONS: Although hypertension is associated with worse cognitive function,
      behavioural symptoms and hippocampal glucose hypometabolism, it is not associated
      with evidence of increased amyloid or tau pathology. Effective management of
      hypertension may potentially have a therapeutic role in the alleviation of
      symptoms in AD.

PMID- 28752645
TI  - Effect of pumping pressure on onset of lactation after caesarean section: A
      randomized controlled study.
AB  - Caesarean section is associated with weaker newborn suction pressure. This
      nonblinded, randomized trial explored the effect of suction pressures generating
      by a breast pump on mothers' onset of lactation and milk supply after caesarean
      section. A high pressure group (-150 mmHg), a low pressure group (-100 mmHg), and
      a control group (none) were generated under computer random assignment with
      concealed allocation in 2 tertiary hospitals. The breast pumping began within 2
      hr after caesarean operation (6 times a day and 30 min per time) until onset of
      lactation. The primary outcomes were the timing of onset of lactation, milk
      supply, and mother's satisfaction in lactation, using both intention-to-treat and
      per-protocol analyses. The secondary endpoints were the pumping-related pain,
      nipple injury, and maternal fatigue. All 164 women randomized were included in
      analysis. The breast pumping at -150 mmHg optimally advanced the timing of the
      onset of lactation and increased daytime milk supply. The pumping also appeared
      to boost mothers' confidence in lactation. The results in the per-protocol
      population (n = 148) were consistent with those of intention-to-treat population
      (n = 164). However, the pumping aggravated maternal nipple pain and fatigue,
      though there was no statistical significance. The findings suggest that a higher
      pumping pressure within the range of normal vaginally born infant suction could
      promote onset of lactation and milk supply among mothers giving birth by
      caesarean section. The pumping could also enhance mothers' confidence in
      breastfeeding.

PMID- 28752646
TI  - Comparing Direct and Video Laryngoscopy for Prehospital Intubation: Can Meta
      analysis Provide an Exact Solution?

PMID- 28752647
TI  - Palladium-Catalyzed Alkylation with Alkyl Halides by C(sp3 )-H Activation.
AB  - Utilizing halogens as traceless directing goups represents an attractive strategy
      for C-H functionalization. A two C-H alkylation system, initiated by the
      oxidative addition of organohalides to Pd0 , has been developed. The first
      reaction involves an intermolecular alkylation of palladacycles to form C(sp3 )
      C(sp2 ) bonds followed by C(sp2 )-H activation/cyclization to deliver alkylated
      benzocyclobutenes as the final products. In the second reaction, two C-C bonds
      are formed by the reaction of palladacycles with CH2 Br2 , and provides a facile
      and efficient method for the synthesis of indanes. The alkylated benzocyclobutene
      products can be transformed into tricyclic hyrocarbons, and the indane
      derivatives are essential structural motifs in bioactive and odorant molecules.

PMID- 28752648
TI  - Foetal fractional thigh volume: an early 3D ultrasound marker of neonatal
      adiposity.
AB  - BACKGROUND: The predisposition for obesity is suggested to originate in the
      prenatal period. Prenatal markers are needed to identify foetuses at risk for
      neonatal adiposity, as early marker of childhood obesity. OBJECTIVE: The aim of
      this study is to assess the association between foetal fractional thigh volume
      (TVol) and neonatal percentage fat mass from mid-gestation onward. METHODS: In
      this perinatal cohort study, singleton pregnancies with term born infants were
      included. Foetal TVol was measured on three-dimensional ultrasound scans (3D US)
      obtained at 22, 26 and 32 weeks of gestation. Neonatal body composition
      measurement (percentage body fat (%BF)) was planned between 42+0 and 42+6 -week
      postmenstrual age. Cross-sectional and longitudinal linear regression analyses
      were performed. RESULTS: Seventy-nine mother-child pairs were included. Median
      (interquartile range) TVol increased from 7.6 (7.1; 8.5) cm3 at 22 weeks to 36.5
      (33.8; 40.9) cm3 at 32 weeks. Median neonatal %BF was 14.3% (11.7; 17.0). TVol at
      22 weeks (beta = -1.58, 95% CI -2.45; -0.70, explained variance 31%) was
      negatively associated with %BF, but no associations were found at 26 and 32 weeks
      of gestation. TVol growth between 22 and 32 weeks of gestation (explained
      variance 18%) was also statistically significantly negatively associated with
      %BF. CONCLUSIONS: Foetal TVol is a promising 3D US marker for prediction of
      neonatal adiposity from mid-gestation onward.

PMID- 28752649
TI  - Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter
      Orange) Extract and p-Synephrine.
AB  - Citrus aurantium L. (bitter orange) extracts that contain p-synephrine as the
      primary protoalkaloid are widely used for weight loss/weight management, sports
      performance, appetite control, energy, and mental focus and cognition. Questions
      have been raised about the safety of p-synephrine because it has some structural
      similarity to ephedrine. This review focuses on current human, animal, in vitro,
      and mechanistic studies that address the safety, efficacy, and mechanisms of
      action of bitter orange extracts and p-synephrine. Numerous studies have been
      conducted with respect to p-synephrine and bitter orange extract because ephedra
      and ephedrine were banned from use in dietary supplements in 2004. Approximately
      30 human studies indicate that p-synephrine and bitter orange extracts do not
      result in cardiovascular effects and do not act as stimulants at commonly used
      doses. Mechanistic studies suggest that p-synephrine exerts its effects through
      multiple actions, which are discussed. Because p-synephrine exhibits greater
      adrenergic receptor binding in rodents than humans, data from animals cannot be
      directly extrapolated to humans. This review, as well as several other
      assessments published in recent years, has concluded that bitter orange extract
      and p-synephrine are safe for use in dietary supplements and foods at the
      commonly used doses. Copyright (c) 2017 The Authors Phytotherapy Research
      Published by John Wiley & Sons Ltd.

PMID- 28752650
TI  - Adolescent alcohol and cannabis use in Iceland 1995-2015.
AB  - INTRODUCTION: Over the past two decades, alcohol consumption of Icelandic
      adolescents has decreased dramatically. The aim of this study was to quantify the
      extent of this reduction and compare it with the trend in cannabis use over a 20
      year period and to identify possible explanations. METHODS: We used data from the
      Icelandic participants to the European School Survey Project on Alcohol and Other
      Drugs study (collected via paper-and-pencil questionnaires in classrooms). The
      sample included all students in the 10th grade (54-89% response rate). RESULTS:
      The percentage of participants who had never used alcohol during their lifetime
      rose from 20.8% in 1995 to 65.5% in 2015. Similarly, there was a decline in the
      proportion of students who had consumed alcohol 40 times or more, from 13.7% to
      2.8%. During the same period, the number of students who had never used cannabis
      rose from 90.2% to 92.0%. In contrast, we found a small, but statistically
      significant, increase in the prevalence of those who had used cannabis 40 times
      or more, from 0.7% in 1995 to 2.3% in 2015. Parental monitoring increased
      markedly between 1995 and 2015, but availability of alcohol decreased. Perceived
      access to cannabis and youth attitudes towards substance use remained unchanged.
      DISCUSSION: Although Iceland has enjoyed success in lowering alcohol use among
      adolescents over the past decades, and somewhat fewer claim to have ever tried
      cannabis, there has been a threefold increase among heavy users of cannabis.
      Increased parental monitoring and decreased availability of alcohol explain some
      of the changes seen.

PMID- 28752651
TI  - Amine-Urea-Mediated Asymmetric Cycloadditions between Nitrile Oxides and o
      Hydroxystyrenes by Dual Activation.
AB  - The first example of asymmetric 1,3-dipolar cycloadditions between nitrile oxides
      and o-hydroxystyrenes, mediated by cinchona-alkaloid-based amine-ureas is
      reported. The method is based on a dual activation involving both LUMO and HOMO
      activations. In addition to the stoichiometric asymmetric induction, a catalytic
      amount of amine-urea enables the cycloadditions to proceed in an enantioselective
      manner. Computational studies strongly support the HOMO activation of o
      hydroxystyrenes and LUMO activation of nitrile oxides by hydrogen-bonding
      interactions with the Bronsted acid/base bifunctional catalyst.

PMID- 28752652
TI  - Y-27632 simplifies the isolation procedure of human primary epidermal cells by
      selectively blocking focal adhesion of dermal cells.
AB  - Primary skin epidermal cells isolation and in vitro expansion culture have been
      widely used for laboratory research and clinical applications. The conventional
      methods involving sequential enzymatic digestion of adult tissues have given low
      cell recovery rate and reduced cell viability. We report here an advanced method
      for human primary epidermal progenitor cells isolation from skin tissues
      including the Rho kinase inhibitor Y-27632. Compared with traditional protocols,
      the current protocol is simple, easy, and faster; moreover, it gives a greater
      yield of integrin-expressing epithelial stem cells. In addition, our new
      methodology does not require a separation of epidermis from dermis because the
      medium selectively blocks focal adhesion and growth of dermal cells. Importantly,
      the cells isolated from this method can maintain their regeneration potential and
      quickly reconstitute a mature human skin in vivo after grafting onto nude mice.
      In brief, we describe here a simple (one step) and serum-free method for
      isolating primary epidermal stem cells from adult tissues. The isolated cells may
      be widely used for both laboratory studies and clinical application, especially
      in the field of tissue engineering and regeneration.

PMID- 28752653
TI  - Who often feels lonely? A cross-sectional study about loneliness and its related
      factors among older home-dwelling people.
AB  - AIM AND OBJECTIVES: To investigate the prevalence of individuals who often feel
      lonely among a sample of Norwegian older home-dwelling people aged >=65 years
      old, as well as to identify any possible factors explaining their loneliness.
      BACKGROUND: Loneliness is known to be common among older people. To identify
      those older adults who are lonely, and to acquire knowledge about the complexity
      of their loneliness, is important to provide them with adequate help and support.
      DESIGN: This study employed a cross-sectional design. METHOD: A questionnaire was
      mailed to a randomised sample of 6,033 older home-dwelling persons aged >=65
      years. A total of 2,052 persons returned the questionnaire and were included in
      the study. The questionnaire consisted of questions asking whether the subjects
      often felt lonely or not, as well as health-related and background questions and
      instruments to measure the participants' sense of coherence, mental problems,
      nutritional screening and self-care ability. The data were analysed using
      univariate and multivariate statistical methods. RESULTS: A total of 11.6% of the
      participants reported often feeling lonely. Six factors emerged to be
      independently associated with often feeling lonely among the respondents: Living
      alone, not being satisfied with life, having mental problems, a weak sense of
      coherence, not having contact with neighbours and being at risk for
      undernutrition. CONCLUSIONS: The study shows that often feeling lonely among
      older home-dwelling persons is a health-related problem that includes social,
      psychological and physical aspects. Moreover, these persons have limited
      resources to overcome feelings of loneliness. IMPLICATIONS FOR PRACTICE: Lasting
      loneliness among older home-dwelling persons requires an overall, person-centred
      and time-consuming approach by nurses. Nurses with advanced knowledge on
      geriatric nursing may be required to offer appropriate care and support.
      Healthcare leaders and politicians should offer possibilities for adequate
      assessment, support and help.

PMID- 28752654
TI  - Land use and mobility during the Neolithic in Wales explored using isotope
      analysis of tooth enamel.
AB  - OBJECTIVES: The nature of land use and mobility during the transition to
      agriculture has often been debated. Here, we use isotope analysis of tooth enamel
      from human populations buried in two different Neolithic burial monuments,
      Penywyrlod and Ty Isaf, in south-east Wales, to examine patterns of land use and
      to evaluate where individuals obtained their childhood diet. MATERIALS AND
      METHODS: We employ strontium (87 Sr/86 Sr) and oxygen (delta18 O) and carbon
      (delta13 C) isotope analysis of enamel from adjacent molars. We compare strontium
      isotope values measured in enamel to locally bioavailable 87 Sr/86 Sr values. We
      combine discussion of these results with evaluation of new radiocarbon dates
      obtained from both sites. RESULTS: The majority of enamel samples from Penywyrlod
      have strontium isotope ratios above 0.7140. In contrast, the majority of those
      from Ty Isaf have 87 Sr/86 Sr values below 0.7140. At Penywyrlod oxygen isotope
      ratios range between 25.9 and 28.2 0/00 (mean 26.7 +/- 0.6 0/00, 1sigma, n = 15)
      and enamel delta13 Ccarbonate values range between -18.0 and -15.0 0/00 (mean 
      16.0 +/- 0.8 0/00, 1sigma, n = 15). At Ty Isaf oxygen isotope ratios exhibited by
      Neolithic individuals range between 25.4 and 27.7 0/00 (mean 26.7 +/- 0.6 0/00,
      1sigma, n = 15) and enamel delta13 Ccarbonate values range between -16.9 and 
      14.9 0/00 (mean -16.0 +/- 0.6 0/00, 1sigma, n = 15). DISCUSSION: The strontium
      isotope results suggest that the majority of individuals buried at Penywyrlod did
      not source their childhood diet locally. One individual in this group has
      strontium isotope ratios that exceed all current known biosphere values within
      England and Wales. This individual is radiocarbon dated to the first few
      centuries of the 4th millennium BC, consistent with the period in which
      agriculture was initiated in Wales: the results therefore provide evidence for
      migration during the transition to farming in Wales. In contrast, all individuals
      sampled from Ty Isaf post-date the period in which agriculture is considered to
      have been initiated and could have sourced their childhood diet from the local
      region in which they were buried.

PMID- 28752656
TI  - The relationship between professional communication competences and nursing
      performance of critical care nurses in South Korea.
AB  - BACKGROUND: Ineffective communication of critical care nurses can lead to higher
      levels of burnout and negatively affect quality of patient care and patient
      outcomes such as higher mortality. AIM: The purpose of this study is to describe
      the relationship between professional communication competences and nursing
      performance of critical care nurses in South Korea. METHOD: This cross-sectional
      study collected data on 197 intensive care unit staff nurses in 3 tertiary
      academic medical centres in South Korea from July to November 2014. RESULTS: In
      the hierarchical regression analysis, the professional communication competences
      were the only significant predictors of nursing performance after adjusting for
      sociodemographic characteristics. In addition, the greater professional
      communication competences of nurses were associated with being older and having a
      higher education level, more years of overall clinical and intensive care unit
      experience, and a higher monthly salary. CONCLUSION: Our findings indicate that
      communication skills-related training should be included in the practical
      education to improve nursing performance for the quality of intensive care.
      Further research is needed to identify the comprehensive factors on professional
      communication competences of nurses in intensive care units.

PMID- 28752655
TI  - Predictors of Emerging Suicide Death Among Military Personnel on Social Media
      Networks.
AB  - Suicide is a leading cause of death in the United States and is the second
      leading cause of death in the U.S. military. Previous research suggests that data
      obtained from social media networks may provide important clues for identifying
      at-risk individuals. To test this possibility, the social media profiles from 315
      military personnel who died by suicide (n = 157) or other causes (n = 158) were
      coded for the presence of stressful life situations (i.e., triggers), somatic
      complaints or health issues (i.e., physical), maladaptive or avoidant coping
      strategies (i.e., behaviors), negative mood states (i.e., emotion), and/or
      negative cognitive appraisals (cognition). Content codes were subsequently
      analyzed using multilevel models from a dynamical systems perspective to identify
      temporal change processes characteristic of suicide death. Results identified
      temporal sequences unique to suicide, notably social media posts about triggers
      followed by more posts about cognitions, posts about cognitions followed by more
      posts about triggers, and posts about behaviors followed by fewer posts about
      cognitions. Results suggest that certain sequences in social media content may
      predict cause of death and provide an estimate of when a social media user is
      likely to die by suicide.

PMID- 28752657
TI  - Maternal executive function, infant feeding responsiveness and infant growth
      during the first 3 months.
AB  - BACKGROUND: There is limited research in young infants, particularly <3 months of
      age, on maternal feeding practices in spite of increasing evidence that early
      weight gain velocity is a determinant of later obesity risk. OBJECTIVE: To
      examine associations between maternal executive function (cognitive control over
      one's own behaviour), maternal feeding decisions and infant weight and adiposity
      gains. METHODS: We used a checklist to assess cues mothers use to decide when to
      initiate and terminate infant feedings at 2 weeks and 3 months of age (N = 69).
      Maternal executive function was assessed using the NIH Toolbox Cognition Battery
      subtests for executive function and infant body composition using air
      displacement plethysmography. RESULTS: Mothers with higher executive function
      reported relying on fewer non-satiety cues at 2 weeks of age (beta = -0.29, p =
      0.037) and on more infant hunger cues at 3 months of age (beta = 0.31, p = 0.018)
      in their decisions on initiating and terminating feedings. Responsive feeding
      decisions, specifically the use of infant-based hunger cues at 3 months, in turn
      were associated with lower gains in weight-for-length (beta = -0.30, p = 0.028)
      and percent body fat (beta = -0.2, p = 0.091; non-covariate adjusted beta = 
      0.27, p = 0.029). CONCLUSIONS: These findings show both an association between
      maternal executive function and responsive feeding decisions and an association
      between responsive feeding decisions and infant weight and adiposity gains. The
      causal nature and direction of these associations require further investigation.

PMID- 28752659
TI  - Editorial.

PMID- 28752658
TI  - Controlling hypertension and reducing its associated morbidity and mortality in
      the Caribbean: implications of race and ethnicity.
AB  - Cardiovascular diseases and stroke, especially hypertension, represent a
      significant global disease burden for both morbidity and mortality, with a
      disproportionately higher impact in vulnerable low- to middle-income countries.
      International initiatives such as the Centers for Disease and Prevention and the
      Pan American Health Organization Standardized Hypertension Treatment Project have
      been developed to address this burden on the Caribbean and Latin America
      populations. The disparity in disease burden observed in low- to middle-income
      countries is explained, in part, by differences in disease risks for different
      racial and ethnic groups with high blood pressure more prevalent and hypertension
      related morbidity significantly higher in men and women of African heritage. In
      addition to the race and ethnic differences in indicators of socioeconomic
      status, access to care and health service delivery, the physiologic mechanism of
      high blood pressure including salt-sensitivity, may also play a significant role
      in the disparities in hypertension and hypertension-related outcomes. This
      article focuses on potential racial and ethnic differences in influences on the
      pathophysiology of hypertension in the Caribbean region of the world. The
      identification of such differences may be used in the development of population
      hypertension control strategies and treatment approach that address the excess
      disease burden in these populations. The consideration of strategies, such as
      salt reduction and hypertension awareness and treatment, are particularly
      relevant to the high-risk Caribbean region.

PMID- 28752660
TI  - Changes in psychopharmacological management of persons with borderline
      personality disorder.

PMID- 28752661
TI  - Left ventricular torsion assessed by two-dimensional echocardiography speckle
      tracking as a predictor of left ventricular remodeling and short-term outcome
      following primary percutaneous coronary intervention for acute myocardial
      infarction: A single-center experience.
AB  - AIMS: Left ventricular (LV) torsion is a novel method to assess systolic LV
      function. This study aimed at exploring the utility of 2D speckle tracking-based
      assessment of left ventricular torsion in patients with acute myocardial
      infarction (AMI) undertaking primary percutaneous intervention (pPCI) in
      predicting left ventricular remodeling. METHODS AND RESULTS: The study included
      115 patients (mean+/-SD, age 52.2+/-9.67, males 84.3%) who underwent pPCI for
      AMI. Echocardiographic assessment of LV torsion by two-dimensional speckle
      tracking was performed early after the index pPCI. Patients underwent repeat
      echocardiography at 6 months to detect remodeling. LV torsion in the acute
      setting was significantly lower in those who demonstrated LV remodeling at follow
      up compared to those without remodeling (7.56+/-1.95 vs 15.16+/-4.65; P<.005).
      Multivariate analysis identified peak CK & CK-MB elevation (beta=-0.767 and 
      0.725; P<.001), SWMA index (beta=-0.843; P<.001), and Simpson's derived LV
      ejection fraction (LVEF; beta=0.802; P<.001) as independent predictors of
      baseline LV torsion. It also identified peak LV torsion (beta: 0.27; 95% CI: 0.15
      0.5, P=.001) and SWMA index (beta: 1.07, 95% CI: 1.03-1.12, P=.005) as
      independent predictors of LV remodeling. Baseline Killip's grades II and higher
      (beta: 48.6; 95% CI 5.5-428, P<.001) and diabetes mellitus (beta: 29.7; 95% CI
      1.1-763, P<.05) were independent predictors of mortality. CONCLUSION: Left
      ventricular torsion in acute MI setting is impaired and predicts subsequent LV
      remodeling at 6-month follow-up.

PMID- 28752662
TI  - A Bayesian approach to solve proton stopping powers from noisy multi-energy CT
      data.
AB  - PURPOSE: To propose a new formalism allowing the characterization of human
      tissues from multienergy computed tomography (MECT) data affected by noise and to
      evaluate its performance in estimating proton stopping powers (SPR). METHODS: A
      recently published formalism based on principal component analysis called
      eigentissue decomposition (ETD) is adapted to the context of noise using a
      Bayesian estimator. The method, named Bayesian ETD, uses the maximum a posteriori
      fractions of eigentissues in each voxel to determine physical parameters relevant
      for proton beam dose calculation. Simulated dual-energy computed tomography
      (DECT) data are used to evaluate the performance of the proposed method to
      estimate SPR and to compare it to the initially proposed maximum-likelihood ETD
      and to a state-of-the-art rhoe  - Z formalism. To test the robustness of each
      method towards clinical reality, three different levels of noise are implemented,
      as well as variations in elemental composition and density of reference tissues.
      The impact of using more than two energy bins to determine SPR is also
      investigated by simulating MECT data using two to five energy bins. Finally, the
      impact of using MECT over DECT for range prediction is evaluated using a
      probabilistic model. RESULTS: For simulated DECT data of reference tissues, the
      Bayesian ETD approach systematically gives lower root-mean-square (RMS) errors
      with negligible bias. For a medium level of noise, the RMS errors on SPR are
      found to be 2.78%, 2.76% and 1.53% for rhoe  - Z, maximum-likelihood ETD, and
      Bayesian ETD, respectively. When variations are introduced to the elemental
      composition and density, all implemented methods give similar performances at low
      noise. However, for a medium noise level, the proposed Bayesian method
      outperforms the two others with a RMS error of 1.94%, compared to 2.79% and 2.78%
      for rhoe  - Z and maximum-likelihood ETD, respectively. When more than two energy
      spectra are used, the Bayesian ETD is able to reduce RMS error on SPR using up to
      five energy bins. In terms of range prediction, Bayesian ETD with four energy
      bins in realistic conditions reduces proton beam range uncertainties by a factor
      of up to 1.5 compared to rhoe  - Z. CONCLUSION: The Bayesian ETD is shown to be
      more robust against noise than similar methods and a promising approach to
      extract SPR from noisy DECT data. In the advent of commercially available multi
      energy CT or photon-counting CT scanners, the Bayesian ETD is expected to allow
      extracting more information and improve the precision of proton therapy beyond
      DECT.

PMID- 28752663
TI  - Platelet production from induced pluripotent stem cells.
AB  - Ex vivo production of human platelets has been pursued as an alternative measure
      to resolve limitations in the supply and safety of current platelet transfusion
      products. To this end, induced pluripotent stem cells (iPSCs) are considered an
      ideal global source, as they are not only pluripotent and self-renewing, but are
      also available from basically any person, have relatively few ethical issues, and
      are easy to manipulate. From human iPSCs, megakaryocyte (MK) lines with robust
      proliferation capacity have been established by the introduction of specified
      sets of genes. These expandable MKs are also cryopreservable and thus would be
      suitable as master cells for good manufacturing practice (GMP)-grade production
      of platelets, assuring availability on demand and safety against blood-borne
      infections. Meanwhile, developments in bioreactors that physically mimic the in
      vivo environment and discovery of substances that promote thrombopoiesis have
      yielded competent platelets with improved efficiency. The derivation of platelets
      from iPSCs could further resolve transfusion-related alloimmune complications
      through the manufacturing of autologous products and human leukocyte antigen
      (HLA)-compatible platelets from stocked homologous HLA-type iPSC libraries or by
      manipulation of HLAs and human platelet antigens (HPAs). Considering these key
      advances in the field, HLA-deleted platelets could become a universal product
      that is manufactured at industrial level to safely fulfill almost all demands. In
      this review, we provide an overview of the ex vivo production of iPSC-derived
      platelets toward clinical applications, a production that would revolutionize the
      blood transfusion system and lead the field of iPSC-based regenerative medicine.

PMID- 28752664
TI  - Modeling plant interspecific interactions from experiments with perennial crop
      mixtures to predict optimal combinations.
AB  - The contribution of plant species richness to productivity and ecosystem
      functioning is a longstanding issue in ecology, with relevant implications for
      both conservation and agriculture. Both experiments and quantitative modeling are
      fundamental to the design of sustainable agroecosystems and the optimization of
      crop production. We modeled communities of perennial crop mixtures by using a
      generalized Lotka-Volterra model, i.e., a model such that the interspecific
      interactions are more general than purely competitive. We estimated model
      parameters -carrying capacities and interaction coefficients- from, respectively,
      the observed biomass of monocultures and bicultures measured in a large diversity
      experiment of seven perennial forage species in Iowa, United States. The sign and
      absolute value of the interaction coefficients showed that the biological
      interactions between species pairs included amensalism, competition, and
      parasitism (asymmetric positive-negative interaction), with various degrees of
      intensity. We tested the model fit by simulating the combinations of more than
      two species and comparing them with the polycultures experimental data. Overall,
      theoretical predictions are in good agreement with the experiments. Using this
      model, we also simulated species combinations that were not sown. From all
      possible mixtures (sown and not sown) we identified which are the most productive
      species combinations. Our results demonstrate that a combination of experiments
      and modeling can contribute to the design of sustainable agricultural systems in
      general and to the optimization of crop production in particular.

PMID- 28752665
TI  - Salient-but-irrelevant stimuli cause attentional capture in difficult, but
      attentional suppression in easy visual search.
AB  - Search for a shape target is difficult when its shape is similar to the shape of
      the surrounding nontargets and easy when it is dissimilar. We asked whether
      interference from a salient but irrelevant color singleton depended on search
      difficulty as manipulated by target-nontarget similarity. We found that
      interference was strong in difficult searches, and the occurrence of an
      electrophysiological index of attentional selectivity (the N2pc component)
      confirmed that attention was captured by the distractor. In contrast,
      interference from the distractor was weak with easy searches, and the occurrence
      of the PD component confirmed that saliency signals from the distractor were
      suppressed. The results suggest that attentional suppression of salient but
      irrelevant distractors is only possible when search is efficient (i.e., with low
      target-nontarget similarity), otherwise, attentional capture occurs. Further, we
      analyzed the Ppc component, a positivity occurring between 100 and 200 ms after
      stimulus onset contralateral to a salient feature discontinuity. It has been
      suggested that the Ppc reflects bottom-up saliency signals, but we found the Ppc
      to occur only when the salient stimulus was unlikely to be selected, as in
      efficient searches. Thus, attentional requirements modulate the Ppc component.

PMID- 28752666
TI  - Mannich Ketones as Possible Antimycobacterial Agents.
AB  - Twenty-three known unsaturated and fused Mannich ketones and their reduced
      derivatives (amino alcohols) were selected for an antituberculotic study. They
      were screened against several mycobacterial strains including Mycobacterium
      tuberculosis, M. xenopi, and M. gordonae, and minimum inhibitory concentration
      values were also determined using the standard antituberculotic drug isoniazid
      (INH) as a reference. Structure-activity relationships were also studied. The
      mode of action of the test compounds was investigated using transmission electron
      microscopy, high-performance liquid chromatography, and matrix-assisted
      desorption/ionization mass spectrometry. Several test substances proved to be as
      potent as INH, but their antimycobacterial spectra were broader than that of INH.
      Our findings suggest that their mode of action is probably through the inhibition
      of mycobacterial cell wall biosynthesis.

PMID- 28752668
TI  - Comparison of two decellularized dermal equivalents.
AB  - Immunologically inert allogeneic acellular dermal scaffolds provide a matrix with
      molecular architecture close to native tissues, which synthetic scaffolds cannot.
      Not all nature-derived scaffolds possess the same biological and physical
      properties. The different properties of scaffolds supporting cellular growth used
      for manufacturing tissue engineered grafts could lead to different implantation
      results. The scaffold properties should be carefully considered in order to meet
      the expected outcomes of tissue engineered grafts. In this report, we evaluated
      the cellular growth on AlloDerm(r) and Allopatch, 2 acellular scaffolds derived
      from human cadaver skin, using a fabricated 3D organotypic culture with primary
      human oral keratinocytes to produce an ex vivo produced oral mucosa equivalent
      (EVPOME). A well stratified epithelium could be constructed on both scaffolds.
      AlloDerm(r) and Allopatch EVPOMEs were also implanted into severe combined
      immunodeficiency mice to compare the ingrowth of blood vessels into the dermal
      component of the two EVPOMEs. Blood vessel counts were 3.3 times higher (p = .01)
      within Allopatch EVPOMEs than within AlloDerm(r) EVPOMEs. An oral and skin
      keratinocyte co-culture, separated by a physical barrier to create a cell-free
      zone, was used to evaluate cell migration on AlloDerm(r) and Allopatch. Slower
      cell migration was observed on Allopatch than on AlloDerm(r).

PMID- 28752667
TI  - Genetic networks controlled by the bacterial replication initiator and
      transcription factor DnaA in Bacillus subtilis.
AB  - DnaA is the widely conserved bacterial AAA+ ATPase that functions as both the
      replication initiator and a transcription factor. In many organisms, DnaA
      controls expression of its own gene and likely several others during growth and
      in response to replication stress. To evaluate the effects of DnaA on gene
      expression, separate from its role in replication initiation, we analyzed changes
      in mRNA levels in Bacillus subtilis cells with and without dnaA, using engineered
      strains in which dnaA is not essential. We found that dnaA was required for many
      of the changes in gene expression in response to replication stress. We also
      found that dnaA indirectly affected expression of several regulons during growth,
      including those controlled by the transcription factors Spo0A, AbrB, PhoP, SinR,
      RemA, Rok and YvrH. These effects were largely mediated by the effects of DnaA on
      expression of sda. DnaA activates transcription of sda, and Sda inhibits
      histidine protein kinases required for activation of the transcription factor
      Spo0A. We also found that loss of dnaA caused a decrease in the development of
      genetic competence. Together, our results indicate that DnaA plays an important
      role in modulating cell physiology, separate from its role in replication
      initiation.

PMID- 28752669
TI  - Behaviour of 4- to 5-year-old nondisabled ELBW children: Outcomes following group
      based physiotherapy intervention.
AB  - BACKGROUND: Extreme prematurity or extremely low birth weight (ELBW) can
      adversely affect behaviour. Nondisabled ELBW children are at risk of behavioural
      problems, which may become a particular concern after commencement of formal
      education. This study explored the frequency of behavioural and emotional
      problems amongst nondisabled ELBW children at 4 to 5 years of age and whether
      intervention had a positive influence on behaviour. The relationship between
      behaviour, gender, and other areas of performance at 5 years was explored.
      METHODS: Fifty 4-year-old children (born <28 weeks gestation or birth weight
      <1,000 g) with minimal/mild motor impairment were randomly allocated to
      intervention (n = 24) or standard care (n = 26). Intervention was 6 group-based
      physiotherapy weekly sessions and home programme. Standard care was best practice
      advice. The Child Behavior Checklist (CBCL) for preschool children was completed
      at baseline and at 1-year post-baseline. Other measures at follow-up included
      Movement Assessment Battery for Children Second Edition, Beery Visual-Motor
      Integration Test 5th Edition, and Peabody Picture Vocabulary Test 4th Edition.
      RESULTS: The whole cohort improved on CBCL total problems score between baseline
      (mean 50.0, SD 11.1) and 1-year follow-up (mean 45.2, SD 10.3), p = .004. There
      were no significant differences between groups over time on CBCL internalizing,
      externalizing, or total problems scores. The intervention group showed a mean
      difference in total problems score of -3.8 (CI [1.5, 9.1]) between times, with
      standard care group values being -4.4 (CI [1.6, 7.1]). Males had higher total
      problems scores than females (p = .026), although still performed within the
      "normal" range. CBCL scores did not correlate with other scores. CONCLUSIONS: The
      behaviour of nondisabled ELBW children was within the "normal" range at 4 to 5
      years, and both intervention and standard care may have contributed to improved
      behavioural outcomes. Behaviour was not related to performance in other
      developmental domains.

PMID- 28752671
TI  - Graphene-Contacted Ultrashort Channel Monolayer MoS2 Transistors.
AB  - 2D semiconductors are promising channel materials for field-effect transistors
      (FETs) with potentially strong immunity to short-channel effects (SCEs). In this
      paper, a grain boundary widening technique is developed to fabricate graphene
      electrodes for contacting monolayer MoS2 . FETs with channel lengths scaling down
      to ~4 nm can be realized reliably. These graphene-contacted ultrashort channel
      MoS2 FETs exhibit superior performances including the nearly Ohmic contacts and
      excellent immunity to SCEs. This work provides a facile route toward the
      fabrication of various 2D material-based devices for ultrascaled electronics.

PMID- 28752670
TI  - Use of direct oral anticoagulants in patients with atrial fibrillation in
      Scotland: Applying a coherent framework to drug utilisation studies.
AB  - PURPOSE: To report the use of direct oral anticoagulants (DOACs) for stroke
      prevention in patients with atrial fibrillation in Scotland and advocate the
      standardisation of drug utilisation research methods. METHODS: Retrospective
      cohort study using linked administrative data. Patients included those with a
      diagnosis of atrial fibrillation (confirmed in hospital) who received a first
      prescription for a DOAC (dabigatran, rivaroxaban, or apixaban) from September
      2011 to June 2014. Drug utilisation measures included discontinuation,
      persistence, and adherence. RESULTS: A total of 5398 patients (mean CHA2 DS2 
      VASc score 2.98 [SD 1.71], 89.7% with >=5 concomitant medicines) were treated
      with DOACs for a median of 228 days (interquartile range 105-425). Of 35.6% who
      discontinued DOAC treatment, 11.0% switched to warfarin, and 48.3% reinitiated
      DOACs. Persistence after 12 and 18 months was 75.9% and 69.8%, respectively.
      Differences between individual DOACs were observed: Discontinuation rates ranged
      from 20.4% (apixaban) to 60.6% (dabigatran) and 12 months persistence from 60.1%
      (dabigatran) to 85.5% (apixaban). Adherence to treatment with all DOACs was good:
      Overall DOAC median medication refill adherence was 102.9% (interquartile range
      88.9%-115.5%), and 82.3% of patients had a medication refill adherence > 80%.
      CONCLUSIONS: In Scotland, adherence to DOAC treatment was good, and switching
      from DOAC to warfarin was low. However, discontinuation and persistence rates
      were variable-although treatment interruptions were often temporary. To decrease
      the inconsistencies in drug utilisation methods and facilitate meaningful study
      comparison, the use of a coherent framework-using a combination of
      discontinuation, persistence, and adherence-and the standardisation of
      measurements is advocated.

PMID- 28752672
TI  - Risk factors for stomatitis in patients with lymphangioleiomyomatosis during
      treatment with sirolimus: A multicenter investigator-initiated prospective study.
AB  - PURPOSE: Lymphangioleiomyomatosis is a rare lung disease caused by proliferation
      of abnormal smooth muscle-like cells and typically occurs in premenopausal women.
      Sirolimus is now the first-line drug for the treatment of
      lymphangioleiomyomatosis. Sirolimus-induced stomatitis is the most frequent
      adverse event experienced during treatment. To identify risk factors, we
      investigated the association of stomatitis incidence with patient background data
      and treatment parameters, using data from the multicenter long-term sirolimus
      trial. METHODS: Subjects received sirolimus for 2 years at doses adjusted to
      maintain a trough blood level of 5 to 15 ng/mL. The incidence of stomatitis was
      correlated with baseline demographics, clinical characteristics, and changes in
      the longitudinal data. Risk factors at baseline were assessed by using univariate
      and multivariate analyses. RESULTS: The most frequent adverse event was
      stomatitis, with the cumulative rate reaching 88.9% by 9 months, higher than that
      reported in postrenal transplant patients. The repetition, the duration, and the
      severity of stomatitis events were variable among patients. We found that
      patients with low hemoglobin (Hb) (<14.5 g/dL) showed significantly higher
      incidence than those with high Hb (>=14.5 g/dL, P < .01). The cumulative rate for
      stomatitis incidence was significantly associated with a decrease in the mean
      corpuscular volume, while the Hb level was constant; thus, red blood cell count
      in patients increased during the study. CONCLUSIONS: Baseline Hb levels and a
      decrease in mean corpuscular volume during treatment were correlated with the
      incidence of stomatitis.

PMID- 28752673
TI  - Liver haemangiomas and consumptive hypothyroidism in association with three
      cutaneous haemangiomas.

PMID- 28752674
TI  - Association of MICA-129 polymorphism and circulating soluble MICA level with
      rheumatoid arthritis in a south Indian Tamil population.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a clinically heterogeneous chronic
      inflammatory disorder characterized by synovitis leading to joint destruction.
      Both genetic and environmental factors are involved in the pathogenesis of RA.
      Significant dysregulation of NKG2D, an activating receptor of natural killer and
      certain autoreactive T cells as well as its ligand major histocompatibility
      complex class I chain-related gene A (MICA) has been implicated in perpetuating
      the pathology of RA. Since the genetic polymorphism in MICA gene (MICA-129
      met/val polymorphism at codon 129) is known to affect its binding affinity to
      NKG2D, we explored its influence on RA susceptibility and disease severity.
      METHODS: The MICA-129 met/val polymorphism was examined in 270 patients with RA
      and 232 healthy controls by TaqMan 5'-nuclease assay. Serum soluble MICA (sMICA)
      was measured in a subset of 89 patients and 80 controls by enzyme-linked
      immunosorbent assay. RESULTS: We observed that the frequency of MICA-129 val
      allele (73% vs. 65%, Pc = 0.006, odds ratio = 1.48, 95% CI = 1.12-1.95) was
      higher in patients than in controls. sMICA levels were significantly higher in
      patients with RA than in controls (P < 0.0001). sMICA levels were higher in
      patients with val/val genotype than in those with met/val or met/met genotype (P
      = 0.03). The MICA-129 val/val genotype was associated with high titers of sMICA
      in patients with deforming RA phenotype (P = 0.02), suggesting a role in
      determination of severity of RA. CONCLUSION: MICA-129 val/val genotype,
      associated with higher levels of circulating sMICA, may influence disease
      susceptibility and associate with increased severity of RA in south Indian
      Tamils.

PMID- 28752675
TI  - International quality of life, similar but different.

PMID- 28752676
TI  - Fine-needle aspiration findings of a rare hematopoietic neoplasm presenting as
      obstructive jaundice.
AB  - A 51-year-old female who presented with obstructive jaundice was found to have
      masses in the pancreatic head and tail as well as suspicious liver and periaortic
      masses on imaging. Aspiration cytology of the pancreatic tail mass showed
      abundant large single cells with vacuolated eosinophilic cytoplasm, marked
      nuclear pleomorphism, large bizarre irregular nuclei, binucleation, and prominent
      nucleoli. Numerous cells also showed intracytoplasmic black to brown
      pigmentation. A cell block was obtained and extensive immunohistochemical
      staining was performed. S-100, HMB-45, Sox10, pancytokeratin, CK7, RCC antigen,
      synaptophysin, HepPar 1, inhibin, CD45, CD21, and CD123 were negative, making
      melanoma, epithelial malignancies, lymphoma, follicular dendritic and
      plasmacytoid dendritic cell neoplasms less likely. CD4 and CD56 showed partial
      positivity, and CD68, CD163, and CD14 were positive, supporting the diagnosis of
      histiocytic sarcoma. Surgical specimens and immunohistochemistry confirmed the
      cytologic findings. Histiocytic sarcoma is a rare aggressive malignancy of
      histiocytic origin with most cases presenting in adults in extranodal sites, most
      commonly the intestinal tract. Few cases are reported in the literature,
      presenting diagnostic challenges for cytopathologists when seen on fine-needle
      aspiration. We present the first reported case of histiocytic sarcoma presenting
      as a pancreatic mass, diagnosed by endoscopic ultrasound guided fine-needle
      aspiration (EUS-FNA). This entity is rarely described on cytology and arose in a
      location in which EUS-FNA is the diagnostic modality of choice. This case study
      highlights that cytopathologists should be aware of histiocytic sarcoma occurring
      in extranodal locations accessible by EUS-FNA and be familiar with the
      cytomorphologic appearance.

PMID- 28752677
TI  - New findings on phosphodiesterases, MoPdeH and MoPdeL, in Magnaporthe oryzae
      revealed by structural analysis.
AB  - The cyclic adenosine monophosphate (cAMP) signalling pathway mediates signal
      communication and sensing during infection-related morphogenesis in eukaryotes.
      Many studies have implicated cAMP as a critical mediator of appressorium
      development in the rice blast fungus, Magnaporthe oryzae. The cAMP
      phosphodiesterases, MoPdeH and MoPdeL, as key regulators of intracellular cAMP
      levels, play pleiotropic roles in cell wall integrity, cellular morphology,
      appressorium formation and infectious growth in M. oryzae. Here, we analysed the
      roles of domains of MoPdeH and MoPdeL separately or in chimeras. The results
      indicated that the HD and EAL domains of MoPdeH are indispensable for its
      phosphodiesterase activity and function. Replacement of the MoPdeH HD domain with
      the L1 and L2 domains of MoPdeL, either singly or together, resulted in decreased
      cAMP hydrolysis activity of MoPdeH. All of the transformants exhibited phenotypes
      similar to that of the DeltaMopdeH mutant, but also revealed that EAL and L1 play
      additional roles in conidiation, and that L1 is involved in infectious growth. We
      further found that the intracellular cAMP level is important for surface signal
      recognition and hyphal autolysis. The intracellular cAMP level negatively
      regulates Mps1-MAPK and positively regulates Pmk1-MAPK in the rice blast fungus.
      Our results provide new information to better understand the cAMP signalling
      pathway in the development, differentiation and plant infection of the fungus.

PMID- 28752678
TI  - Risk factors and outcome of Thai patients with scleroderma renal crisis: a
      disease duration-matched case control study.
AB  - INTRODUCTION: Data regarding the prevalence, risk factors and outcome of
      scleroderma renal crisis (SRC) in Asian patients with systemic sclerosis (SSc)
      are limited. OBJECTIVE: To determine the prevalence, risk factors and outcomes of
      SRC in Thai SSc patients. METHOD: Medical records of all SSc patients seen at the
      Division of Rheumatology, Chiang Mai University, Thailand, from January 1990 to
      December 2015 were retrospectively reviewed. For each SRC case, a disease
      duration (+/-1 year) matched control (four SSc patient without SRC for each SRC
      patient) was identified. RESULT: Of 608 SSc patients seen during the study
      period, 19 SRC cases were identified, resulting in an SRC prevalence of 3.13%,
      with 76 matched controls. Of the 19 cases, mean +/- SD age and median
      (interquartile range 1-3) disease duration was 56.2 +/- 13.8 years and 5 (3-22)
      months, respectively. Seventeen patients (89.5%) had diffuse cutaneous SSc.
      Twelve patients (63.2%) had hypertensive renal crisis and seven (36.8%) had
      normotensive renal crisis. Multivariate conditional logistic regression analyses
      showed that digital gangrene (adjusted odd ratio [AOR] 31.41, 95% CI = 1.16
      852.23, P = 0.041), current prednisolone dose >= 15 mg/day (AOR 31.22, 95% CI =
      1.59-613.85, P = 0.024), serum albumin < 3 mg/dL (AOR 7.97, 95% CI = 1.49-42.56,
      P = 0.015), and cardiac involvement (AOR = 6.62, 95% CI = 1.08-40.63, P = 0.041)
      were independent risk factors for SRC. Fifteen SRC patients (78.9%) required
      dialysis and 10 (52.6%) died. CONCLUSION: SRC was an uncommon complication in
      Thai patients with SSc, but is associated with high mortality. Digital gangrene,
      current prednisolone dose >= 15 mg/day, serum albumin < 3 mg/dL and cardiac
      involvement were independent risk factors for SRC.

PMID- 28752679
TI  - The effect of intra-articular injection of autologous bone marrow stem cells on
      pain and knee function in patients with osteoarthritis.
AB  - AIM: Management of osteoarthritis (OA) is basically symptomatic. Recently, stem
      cells (SC) have been used in the search for an optimum treatment. We decided to
      conduct a controlled clinical trial to determine if a single intra-articular
      injection of in vivo stimulated bone marrow SC could lead to an improvement in
      pain management and quality of life in patients with knee OA. METHOD: This was a
      prospective, open-label, phase I/II clinical trial to assess the safety and
      efficacy of a single intra-articular injection of autologous stimulated bone
      marrow stem cells (BM-SC) in patients with knee OA. Individuals of both genders
      older than 30 years with confirmed diagnosis of OA who signed informed consent
      were included in two groups: SC group received in vivo BM stimulation with
      subcutaneous administration of granulocyte colony stimulating factor (G-CSF). SC
      were obtained by BM aspiration and administered in a single intra-articular
      injection. The control group received exclusively oral acetaminophen. Visual
      analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index
      scores were performed at 1 week, 1 month and 6 months in both groups. This trial
      was registered in ClinialTrials.gov NCT01485198. RESULTS: A total of 61 patients
      were included. Socio-demographic characteristics, OA grades and initial scores
      were similar in both groups. The BM-SC group showed significant improvement in
      knee pain and quality of life during the 6-month follow-up. CONCLUSION: The study
      demonstrates feasibility and supports efficacy of a completely ambulatory
      procedure in treatment of knee OA.

PMID- 28752680
TI  - Elevated serum interleukin-35 is associated with disease activity in patients
      with systemic lupus erythematosus.

PMID- 28752681
TI  - Spontaneous pneumomediastinum, emphysema, and pulmonary bullae associated with
      refractory Mycoplasma pneumoniae pneumonia in a child.
AB  - We report a 21-month-old child with spontaneous pneumomediastinum (PM),
      emphysema, and pulmonary bullae caused by Mycoplasma pneumonia (M. pneumoniae)
      pneumonia. The patient presented with stubborn dyspnea and wheezing although
      received integrated treatment, including anti-infection, anti-inflammation, and
      intravenous immunoglobulin. This case was unique in that pulmonary bullae kept
      increasing. PM and emphysema were refractory in our patient, which have been
      reported as benign and limited. Surgical intervention was implemented to
      ultimately cure the case. Clinicians should be aware of air leaks in patients
      with M. pneumoniae pneumonia since this complication may be fatal.

PMID- 28752682
TI  - Impairment of Retinoic Acid Signaling in Cornelia de Lange Syndrome Fibroblasts.
AB  - BACKGROUND: Cornelia de Lange syndrome (CdLS) is a rare genetic disorder
      affecting the neurodevelopment, gastrointestinal, musculoskeletal systems. CdLS
      is caused by mutations within NIPBL, SMC1A, SMC3, RAD21, and HDAC8 genes. These
      genes codify for the "cohesin complex" playing a role in chromatid adhesion, DNA
      repair and gene expression regulation. The aim of this study was to investigate
      retinoic acid (RA) signaling pathway, a master developmental regulator, in CdLS
      cells. METHODS: Skin biopsies from CdLS patients and healthy controls were
      cultured and derived primary fibroblast cells were treated with RA or dimethyl
      sulfoxide (vehicle). After RA treatment, cells were harvested and RNA was
      isolated for quantitative real-time polymerase chain reaction experiments.
      RESULTS: We analyzed several components of RA metabolism in a human cell line of
      kidney fibroblasts (293T), in addition to fibroblasts collected from both NIPBL
      mutated patients and healthy donors, with or without RA treatment. In all cases,
      ADH and RALDH1 gene expression was not affected by RA treatment, while CRABP1 was
      induced. CRABP2 was dramatically upregulated upon RA treatment in healthy donors
      but not in CdLS patients cells. CONCLUSION: We investigated if CdLS alterations
      are associated to perturbation of RA signaling. Cells derived from CdLS patients
      do not respond to RA signaling as efficiently as healthy controls. RA pathway
      alterations suggest a possible underlying mechanism for several cellular and
      developmental abnormalities associated with cohesin function. Birth Defects
      Research 109:1268-1276, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28752683
TI  - Preface: mathematics, physics, and engineering in biology.

PMID- 28752684
TI  - Amblyomma sculptum: genetic diversity and rickettsias in the Brazilian Cerrado
      biome.
AB  - Amblyomma sculptum (Ixodida: Ixodidae) Berlese, 1888 is the most important tick
      vector in Brazil, transmitting the bioagent of the most severe form of spotted
      fever (SF) in part of the Cerrado (in the states of Minas Gerais and Sao Paulo).
      In another part of the Cerrado (Central-West region of Brazil), a milder form of
      SF has been recorded. However, neither the rickettsia nor the vector involved
      have been characterized. The aim of the current study was to analyse genetic
      variation and the presence of rickettsia in A. sculptum in Cerrado, from silent
      areas and with the milder form of SF. Samples were subjected to DNA extraction,
      amplification and sequencing of 12S rDNA, cytochrome oxidase subunit II and D
      loop mitochondrial genes (for tick population analyses), and gltA, htrA, ompA and
      gene D (sca4) genes for rickettsia researches. Exclusive haplotypes with low
      frequencies, high haplotype diversity and low nucleotide diversity, star-shaped
      networks and significant results in neutrality tests indicate A. sculptum
      population expansions in some areas. Rickettsia amblyommatis, Candidatus
      Rickettsia andeanae and Rickettsia felis were detected. The A. sculptum diversity
      is not geographically, or biome delimited, pointing to a different potential in
      vector capacity, possibly associated with differing tick genetic profiles.

PMID- 28752685
TI  - Gastrointestinal: Aspergillus granulomatous gastritis.

PMID- 28752686
TI  - Hepatobiliary and Pancreatic: Portal vein stent for local recurrence of bile duct
      cancer.

PMID- 28752687
TI  - Gastrointestinal: Ileo-anal J-pouch intraluminal bridge causing obstruction and
      bleeding.

PMID- 28752688
TI  - Hepatobiliary and Pancreatic: Biliary intra-epithelial neoplasia.

PMID- 28752689
TI  - Gastrointestinal: Biliary tubulovillous adenoma.

PMID- 28752690
TI  - Brexit should not mean Brexit for cytopathology.

PMID- 28752692
TI  - In Reply: Comparing Direct and Video Laryngoscopy for Prehospital Intubation: Can
      Meta-analysis Provide an Exact Solution?

PMID- 28752693
TI  - Comparison between mineralized cancellous bone allograft and an alloplast
      material for sinus augmentation: A split mouth histomorphometric study.
AB  - BACKGROUND: Several grafting materials have been used in sinus augmentation
      procedures including autogenous bone, demineralized freeze-dried bone,
      hydroxyapatite, beta-tricalcium phosphate, anorganic deproteinized bovine bone,
      and combination of these and others. Yet, the issue of the optimal graft material
      for sinus floor augmentation is controversial. PURPOSE: This prospective,
      randomized split-mouth study was undertaken to histomorphometrically compare a
      biphasic calcium phosphate (BCP) alloplastic bone substitute and a human bone
      mineral allograft (freeze-dried bone allograft, FDBA) in patients undergoing
      bilateral maxillary lateral sinus floor augmentation. MATERIAL AND METHODS: Apico
      coronal core biopsies were harvested at 9 months from 26 bilateral sites in 13
      treated patients. Specimens were processed for histological and
      histomorphometrical analyses. RESULTS: Newly formed bone (NB) was evident in all
      specimens with values of 27.5% and 24.0% at the FDBA and BCP sites, respectively
      (P = .331). The residual graft particle values were 12.5% and 25.4% (P = .001),
      and the connective tissue values were 60.0% and 50.6%, respectively. The
      osteoconductive value was 52.6% for the FDBA and 26.7% for the alloplast (P =
      .001). The values for the measured residual graft particles, connective tissue,
      and osteoconductivity, but not for NB, showed highly significant differences
      between the two groups. All sections in the alloplast material showed evidence of
      a light chronic inflammatory infiltrate, mainly comprising lymphocytes and
      multinucleated giant cells. CONCLUSIONS: Both graft materials are suitable for
      sinus floor augmentation, with the allograft material being more osteoconductive.

PMID- 28752694
TI  - Impact of Age on Scleral Buckling Surgery for Rhegmatogenous Retinal Detachment.
AB  - PURPOSE: The purpose of this study is to investigate new prognostic factors in
      associated with primary anatomical failure after scleral buckling (SB) for
      uncomplicated rhegmatogenous retinal detachment (RRD). METHODS: The medical
      records of patients with uncomplicated RRD treated with SB were retrospectively
      reviewed. Eyes with known prognostic factors for RRD, such as fovea-on,
      proliferative vitreoretinopathy, pseudophakia, aphakia, multiple breaks, or media
      opacity, were excluded. Analysis was performed to find correlations between
      anatomical success and various parameters, including age. RESULTS: This study
      analyzed 127 eyes. Binary logistic regression analysis revealed that older age
      (>=35) was the sole independent prognostic factor (odds ratio, 3.5; p = 0.022).
      Older age was correlated with worse preoperative visual acuity (p < 0.001),
      shorter symptom duration (p < 0.001), presence of a large tear (p < 0.001),
      subretinal fluid drainage (p < 0.001), postoperative macular complications (p =
      0.048), and greater visual improvement (p = 0.003). CONCLUSIONS: Older age (>=35)
      was an independent prognostic factor for primary anatomical failure in SB for
      uncomplicated RRD. The distinguished features of RRD between older and younger
      patients suggest that vitreous liquefaction and posterior vitreous detachment are
      important features associated with variation in surgical outcomes.

PMID- 28752695
TI  - Changes in Tear Volume after 3% Diquafosol Treatment in Patients with Dry Eye
      Syndrome: An Anterior Segment Spectral-domain Optical Coherence Tomography Study.
AB  - PURPOSE: To evaluate changes in the tear meniscus area and tear meniscus height
      over time in patients with dry eye syndrome, using anterior segment spectral
      domain optical coherence tomography after the instillation of 3% diquafosol
      ophthalmic solution. METHODS: Sixty eyes from 30 patients with mild to moderate
      dry eye syndrome were included. Tear meniscus images acquired by anterior segment
      spectral-domain optical coherence tomography were analyzed using National
      Institutes of Health's image-analysis software (ImageJ 1.44p). Tear meniscus area
      and tear meniscus height were measured at baseline, 5 minutes, 10 minutes, and 30
      minutes after instillation of a drop of diquafosol in one eye and normal saline
      in the other eye. Changes in ocular surface disease index score, tear film break
      up time, corneal staining score by Oxford schema, and meibomian expressibility
      were also evaluated at baseline, and after 1 week and 1 month of a diquafosol
      daily regimen. RESULTS: Sixty eyes from 30 subjects (mean age, 29.3 years; 8 men
      and 22 women) were included. In eyes receiving diquafosol, tear volume was
      increased at 5 and 10 minutes compared with baseline. It was also higher than
      saline instilled eyes at 5, 10, and 30 minutes. Changes in tear volume with
      respect to baseline were not statistically different after the use of diquafosol
      for 1 month. Ocular surface disease index score, tear film break-up time, and
      Oxford cornea stain score were significantly improved after 1 week and 1 month of
      daily diquafosol instillation, but meibomian expressibility did not change.
      CONCLUSIONS: Topical diquafosol ophthalmic solution effectively increased tear
      volume for up to 30 minutes, compared to normal saline in patients with dry eye
      syndrome.

PMID- 28752696
TI  - Learning Curve for Endoscopic Endonasal Dacryocystorhinostomy.
AB  - PURPOSE: To elucidate the learning curve for endoscopic endonasal
      dacryocystorhinostomy (EE-DCR) based on the results of EE-DCR performed by three
      surgeons at three different tertiary hospitals. METHODS: A retrospective review
      of the medical records of 386 eyes of 337 patients who had undergone EE-DCR by
      three surgeons at three tertiary hospitals and who were available for a >6-month
      postoperative observation period was conducted. The success of a given surgery
      was determined based on the results of a test performed during the patient's last
      outpatient visit to the hospital. The learning curve was identified by dividing
      the patients into four groups (20, 30, 40, and 50 eyes in each respective group)
      and comparing their success rates. RESULTS: The overall success rate of the
      entire study population was 86.3%. The success rates for each of three surgeons
      was 83.3%, 85.6%, and 88.1%, respectively. After dividing the patients into
      groups of 30 eyes each, all three surgeons showed a significant increase in
      surgery success rates after their first group of 30 eyes (p < 0.05). The overall
      success rate excluding the first 30 eyes was 92.9%, and all three surgeons
      exhibited a significantly improved success rate of >90% (A, 94.4%; B, 90.8%; C,
      95.4%). CONCLUSIONS: A surgeon should be required to perform at least 30 EE-DCR
      procedures to obtain stable surgical skill for this procedure.

PMID- 28752697
TI  - Clinical Features of Pregnancy-associated Retinal and Choroidal Diseases Causing
      Acute Visual Disturbance.
AB  - PURPOSE: To report clinical features of patients with retinal and choroidal
      diseases presenting with acute visual disturbance during pregnancy. METHODS: In
      this retrospective case series, patients who developed acute visual loss during
      pregnancy (including puerperium) and visited a tertiary hospital from July 2007
      to June 2015, were recruited by searching electronic medical records. Patients
      were categorized according to the cause of visual loss. Clinical features and
      required diagnostic modalities were analyzed in the retinal and choroidal disease
      group. RESULTS: Acute visual loss occurred in 147 patients; 49 (38.9%) were
      classified into the retinal and choroidal group. The diagnoses included central
      serous chorioretinopathy (22.4%), hypertensive retinopathy with or without pre
      eclampsia (22.4%), retinal tear with or without retinal detachment (18.4%),
      diabetic retinopathy progression (10.2%), Vogt-Koyanagi-Harada disease (4.1%),
      retinal artery occlusion (4.1%), multiple evanescent white dot syndrome (4.1%),
      and others (14.3%). Visual symptoms first appeared at gestational age 25.9 +/-
      10.3 weeks. The initial best-corrected visual acuity (BCVA) was 0.27 +/- 0.39
      logarithm of the minimum angle of resolution (logMAR); the final BCVA after
      delivery improved to 0.13 +/- 0.35 logMAR. Serious visual deterioration (BCVA
      worth than 20 / 200) developed in two patients. Differential diagnoses were
      established with characteristic fundus and spectral-domain optical coherence
      tomography findings in all cases. CONCLUSIONS: In pregnant women with acute
      visual loss, retinal and choroidal diseases are common and could be vision
      threatening. Physicians should be aware of pregnancy-associated retinal and
      choroidal diseases and their clinical features. The differential diagnosis can be
      established with non-invasive techniques.

PMID- 28752698
TI  - Endophthalmitis.
AB  - Endophthalmitis is a rare but severe form of ocular inflammation due to infection
      of the intraocular cavity that can lead to irreversible visual loss if not
      treated properly and timely. It can be classified as exogenous or endogenous
      based on the transmission route of the infectious source. Exogenous
      endophthalmitis occurs when infecting organisms gain entry into the eye via
      direct inoculation, while endogenous endophthalmitis occurs when infectious
      agents hematogenously spread into the eye from a distant focus of infection. The
      diagnosis of endophthalmitis depends mostly on the clinical findings on
      ophthalmological examination. Delayed diagnosis of endogenous endophthalmitis can
      lead to not only visual loss, but also increased risk of mortality. Since ocular
      and systemic symptoms of endophthalmitis are usually non-specific, early
      diagnosis relies on the alertness of clinicians. Early diagnosis and proper
      treatment are keys to saving the eye. Following advances in vitreoretinal
      pharmacotherapy and surgical technology, early surgical intervention is the
      current trend in the management of endophthalmitis.

PMID- 28752699
TI  - Nontuberculous Mycobacterial Infection after Removal of the Exposed
      Hydroxyapatite.

PMID- 28752700
TI  - Effect of Anti-vascular Endothelial Growth Factor Antibody on the Survival of
      Cultured Retinal Ganglion Cells.
AB  - PURPOSE: To investigate the effects of anti-vascular endothelial growth factor
      (VEGF) antibody on the survival of retinal ganglion cell (RGC)-5 cells
      differentiated with staurosporine under oxidative stress. METHODS: We used real
      time polymerase chain reaction and Western blot to confirm the expression of
      VEGF, VEGF receptor (VEGFR)-1 and VEGFR-2 in RGC-5 cells differentiated with
      staurosporine for 6 hours. The differentiated RGC-5 cells were treated with 800
      MUM hydrogen peroxide (H2O2) for 24 hours to induce oxidative stress. Then, the
      survival rate of RGC-5 was confirmed by lactate dehydrogenase assay at each
      concentration (0, 0.01, 0.1, and 1 mg) using bevacizumab as the anti-VEGF
      antibody. The expression of VEGF, VEGFR-1, and VEGFR-2 was confirmed using real
      time polymerase chain reaction. RESULTS: VEGF, VEGFR-1, and VEGFR-2 were all
      expressed in differentiated RGC-5 cells. When RGC-5 cells were simultaneously
      treated with bevacizumab and 800 MUM H2O2, survival of RGC-5 decreased with
      bevacizumab concentration. VEGF expression in RGC-5 cells increased with
      increasing concentration of bevacizumab. Similar patterns were observed for VEGFR
      1 and VEGFR-2, but the degree of increase was smaller than that for VEGF.
      CONCLUSIONS: When bevacizumab was administered to differentiated RGC-5 cells, the
      cell damage caused by oxidative stress increased. Therefore, given these in vitro
      study results, caution should be exercised with bevacizumab treatment.

PMID- 28752701
TI  - [Effects of myeloid specific deficiency of FBXW7 on lung metastasis of murine
      melanoma].
AB  - Objective: To investigate the effects of myeloid-specific deficiency of FBXW7 on
      lung metastasis of murine B16F10 melanoma and its mechanisms. Methods: Mice
      carrying the floxed allele of FBXW7 and lysozyme M-Cre were used for generation
      of mice with myeloid cell-specific deletion of FBXW7. Mouse genotypes were
      examined by genomic DNA PCR. B16F10 cells in PBS were injected into the tail vein
      of Lysm-FBXW7f/f and Lysm+FBXW7 f/f mice. After 14 d, the mice were sacrificed,
      and the lungs were removed and weighed. B16F10 tumor colonies in the lungs were
      counted. The myeloid cells were analyzed by flow cytometry. Results: Myeloid
      specific deficiency of FBXW7 mice were generated successfully, as FBXW7
      expressions in peritoneal macrophages and bone marrow-derived macrophages (BMDMs)
      of Lysm+FBXW7f/f mice were knockdown. Flow cytometry results showed the deletion
      of FBXW7 in myeloid lineages did not affect the development of myeloid immune
      cell subsets. Metastasis was reduced in Lysm+FBXW7 f/f mice compared with control
      mice. The number of tumor colonies was 165+/-42, 122+/-12 respectively. The
      proportion of metastasis-associated macrophages (MAM) in the lungs of Lysm+FBXW7
      f/f mice was reduced [(23.15+/-7.59)% vs (13.13+/-2.26)%], while the proportion
      of resident macrophages was increased [(5.426+/-0.42)% vs (10.42+/-1.90)%]. The
      proportion of myeloid-derived suppressor cells in the lung showed no difference
      between Lysm-FBXW7f/f and Lysm+FBXW7 f/f mice. Conclusion: Myeloid-specific
      deficiency of FBXW7 can inhibit lung metastasis of B16F10 melanoma in mice, and
      the mechanism may be associated with regulation of MAM in the metastatic tumor
      lesions.

PMID- 28752702
TI  - [Synthesis of BODIPY photosensitizers and their photodynamic effect on cancer
      cells].
AB  - Objective: To design and synthesize photosensitizers with different substituents
      and to identify its physicochemical characteritics and photodynamic effect on
      cancer cells. Methods: Two kinds of BODIPY photosensitizers BPOI and BPCI were
      synthesized through condensation reaction between aldehyde and reactive hydrogen
      of pyrrole, followed with electrophilic substitution reaction. Physicochemical
      properties were characterized by 1H NMR, FT-IR and UV-visible absorption spectra
      and fluorescence emission spectra. The ability to produce reactive oxygen species
      was detected by BPDF and DCFH-DA. Photodynamic therapy effect on rat glioma C6
      cells in vitro was determined by MTT method. Results: Two kinds of BODIPY
      photosensitizers BPOI and BPCI were successfully synthesized with different
      substituents, which were confirmed by 1H NMR, FT-IR. Both materials had low
      toxicity and could be readily taken up by tumor cells. The ability of synthesized
      photosensitizers to produce reactive oxygen species was strongly influenced by
      solvent polarity when the substituent was electron-donating group, while no
      effect was found when the substituent was electron-withdrawing group. Conclusion:
      Photosensitizer BPOI with electron-donating substituent produces reactive oxygen
      species with a slow rate in a highly polar environment, while greatly enhanced
      this effect in a low polarity environment, which is expected to be used for
      environmental-selective photodynamic therapy in tumor cells.

PMID- 28752703
TI  - [Synthesis, characterization and antitumor activity of 5-fluorouracil
      nicotinamide cocrystal].
AB  - Objective: To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to
      investigate its physicochemical and biological properties. Methods: The cocrystal
      of 5-Fu-NCT was prepared through the cooling technology. PXRD, NMR, FTIR and DSC
      were used to characterize the structure of 5-FU-NCT cocrystal. Solubility was
      measured by HPLC method. Drug resistant human liver cancer BEL-7402/5-FU cells
      were treated with 5-FU-NCT cocrystal, the inhibition effect was tested by MTT and
      HE staining, and cancer cell migration was determined by scratch test. Results:
      According to PXRD, NMR, FTIR and DSC results, the cocrystal of 5-Fu-NCT had been
      synthesized successfully. The characteristic diffraction peaks (2theta/ degrees )
      of the cocrystal were 16.4, 20.4, 22.3, 27.9 and 30.1. The solubility of 5-FU-NCT
      was 13.5 g/L as measured by HPLC. The antitumor activity tests showed that 5-FU
      NCT cocrystal enhanced anticancer effect of 5-FU, and the IC50 of 5-FU and 5-FU
      NCT was 129.6 MUg/mL and 42.6 MUg/mL, respectively. Conclusion: 5-Fu-NCT
      cocrystal have been synthesized successfully through the cooling technology and
      it shows an enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU
      cells.

PMID- 28752704
TI  - [Preparation, characterization and cytology study of Pluronic-PEI micelles].
AB  - Objective: To prepare and characterize Pluronic-PEI micelles as a drug/gene
      delivery system. Methods: We used the low-molecular-weight PEI as a cross-linking
      agent to prepare the Pluronic-PEI micelles. The particle size, zeta potential and
      critical micelle concentration (CMC) were measured by dynamic light scattering
      (DLS) and pyrene fluorescence probe. The cytotoxicity, transfection efficiency
      and the impact on the intracellular ATP and P-gp levels of Pluronic-PEI micelles
      were investigated at the cellular level. Results: Pluronic-PEI micelles were
      successfully prepared with a suitable particle size (120-180 nm), zeta potential
      (+6-+9 mv), and a good ability to carry the drug/gene. An in-vitro study showed
      that Pluronic-PEI had low cytotoxicity, and the P123-PEI600 possessed high gene
      transfection efficiency and could downregulate the intracellular ATP and P-gp
      levels. Conclusion: Pluronic-PEI is a good drug/gene delivery system, and P123
      PEI600 is an ideal vector, which may be used in the combination therapy for
      reversing multidrug resistance.

PMID- 28752705
TI  - [Bacterial outer membrane vesicles as nano carriers to study immunological
      activities].
AB  - Objective: To prepare a nano-carrier based on combining bacterial outer membrane
      vesicles (OMV) with three block polymer pluronic F127 (PEO100-PPO65-PEO100) (OMV
      F127) and to investigate its immunological activity. Methods: Attenuated
      salmonella (sal) was cultivated. OMV were separated by centrifugal
      ultrafiltration or ultrasonication, and OMV-F127 was prepared by mechanical
      extrudation method. The protein contents and compositions were tested with BCA
      and SDS-PAGE; the morphology of OMV, F127 and OMV-F127 were observed with FM and
      TEM; the particle sizes and their zeta potential were determined with DLS. Mouse
      macrophage RAW246.7 cells were treated with OMV-F127 (50 MUg/mL, 100 MUg/mL) in
      vitro, and the concentrations of IL-12, TNF-alpha and IFN-gamma in culture
      supernatant were measured with ELISA kits. Results: The contents of protein in
      separated OMV by centrifugal ultrafiltration and ultrasonication were 2.8 mg/mL
      and 2.7 mg/mL, respectively. SDS-PAGE showed the marker protein OmpF/C in OMV.
      Under the FM and TEM, ball-like structure of F127 and OMV-F127 was observed. Size
      analysis revealed that the diameters of OMV, F127 and OMV-F127 were 72+/-2 nm,
      90+/-3 nm and 92+/-2 nm, respectively. ELISA tests revealed that OMV-F127
      significantly stimulated the secretion of IL-12, TNF-alpha and IFN-gamma in
      RAW246.7 cells. Conclusion: A nano-carrier based on bacterial outer membrane
      vesicles has been prepared, which can stimulate the secretion of cytokines and
      may have immunomodulatory effects.

PMID- 28752706
TI  - [Preparation, characterization and antitumor of cyclodextrin inclusion of an anti
      cancer drug regorafenib].
AB  - Objective: In order to improve the drug's solubility, dissolution and
      bioavailability, RG-beta-CD, RG-gamma-CD and RG-Hp-beta-CD were prepared by co
      crystallization between Regorafenib (RG) and beta-cyclodextrin (beta-CD), gamma
      cyclodextrin (gamma-CD) and Hydroxypropyl-beta-cyclodextrin (Hp-beta-CD).
      Methods: Three inclusion complexes were prepared by recrystallization and solvent
      evaporation methods and characterized by fourier transform infrared spectroscopy
      (FT-IR), thermal analysis (TG), differential scanning calorimetry (DSC), powder X
      ray diffraction (PXRD), 1H nuclear magnetic resonance (1H-NMR), nuclear
      overhauser effect spectroscopy (NOESY). In vivo experiments, tumor suppression
      assay were made with SW620 colon cancer cell. Results: The ability of solubility
      and dissolution were improved after inclusion with three kinds of cyclodextrins.
      The regorafenib-beta-cyclodextrin inclusionis proved to have the best stability.
      The less enhanced was regorafenib-gamma-cycl-odextrin inclusion. The best
      dissolution of regorafenib-beta-cyclodextrin inclusion complex was to bring as
      the tumor suppression assay, the result shows that regorafenib inclusion with
      beta-cyclodextrin is better than regorafenib itself. Conclusion: The
      bioavailability of regorafenib by inclusion with cyclodextrin can enhance due to
      the solubility enhancement of RG, which can provide an effective method for
      improving solubility and dissolution of insoluble drug in clinical medication.

PMID- 28752707
TI  - [Characterization and stability of S (-) pantoprazole sodium hydrates].
AB  - Objective: To study the characteristics and stability of new S(-) pantoprazole
      sodium hydrates. Methods: The X-ray single crystal diffractometer (SXRD), X-ray
      powder diffractometer (PXRD), thermogravimetric analysis (TG) and infrared
      spectrometry (IR) were used to characterize S(-) pantoprazole sodium hydrates.
      The stability of the hydrates was evaluated by high temperature test,affecting
      factors test and accelerated test. Results: The crystalline water in S(-)
      pantoprazole sodium hydrates were very easy to lose and obtain, but crystal
      structure was not changed significantly. The transition from S(-) pantoprazole
      sodium trihydrate to S(-) pantoprazole sodium hemipentahydrate occurred at
      approximately 40 C and reversible transitions from hemipentahydrate to trihydrate
      occurred at high humidity. Two hydrates had no significant difference in
      accelerated test. Conclusion: The crystal structure of the two hydrates are
      almost the same, hemipentahydrate is more stable than trihydrates at high
      temperature or at exposure to light(at 4500 +/- 500 lx).

PMID- 28752708
TI  - [Advances in nanoparticle-targeting tumor associated macrophages for cancer
      imaging and therapy].
AB  - Tumor tissues are composed of tumor cells and complicate microenvironment. Tumor
      associated macrophages (TAMs) as an important component in tumor
      microenvironment, play fundamental roles in tumor progression, metastasis and
      microenvironment regulation. Recently, studies have found that nanotechnology, as
      an emerging platform, provides unique potential for cancer imaging and therapy.
      With the nanotechnology, TAMs imaging presents direct evidence for cancer
      development, progression, and the effectiveness of cancer treatments; it also can
      regulate the immunosuppression of tumor microenvironment and improve therapeutic
      efficiency through TAMs targeted killing or phenotypic transformation. In this
      article, we illustrate the function of TAMs and review the latest development in
      nano-carriers and their applications in tumor associated macrophage targeting
      cancer imaging and therapy.

PMID- 28752709
TI  - [Expression and clinical significance of DNAJB11 in epithelial ovarian cancer].
AB  - Objective: To study the expression of DNAJB11 protein in epithelial ovarian
      cancer tissues and its clinical significance. Methods: Immunohistochemistry was
      used to examine DNAJB11 expressions in 105 tissue specimens of ovarian epithelial
      carcinoma, 23 normal ovarian tissues, 17 tissues of benign tumor, and 13 tissues
      of of borderline tumor. The correlations between protein expression and
      clinicopathological factors were analyzed by Chi square test.The correlations
      between protein expression and survival were analyzed by Kaplan-Meier and Cox
      regression. Results: Positive expression of DNAJB11 protein was observed in 0.0%
      in normal ovary and benign tumor, 7.69% in borderline tumor, and 78.10% in
      epithelial ovarian cancer, respectively. Positive expression of DNAJB11 protein
      was significantly higher than the rest of the ovarian tissues and normal ovarian
      tissues (P<0.001).Higher expression of DNAJB11 was more prevalent in tissues from
      patients with advanced FIGO stages, high serum CA125, poor histological
      differentiation, and serous cancer. Kaplan-Meier curves revealed that higher
      expression of DNAJB11 was significantly associated with poor disease-free
      survival and overall survival.Multivariate survival analysis revealed that strong
      positive expression of DNAJB11 was an independent prognostic factor for disease
      free survival and overall survival. Conclusion: DNAJB11 may play a role in
      tumorigenesis and progression of epithelial ovarian cancer.Strong positive
      expression of DNAJB11 was an independent prognostic factor in epithelial ovarian
      cancer.

PMID- 28752710
TI  - [Nicotinamide regulates blood glucose level and affects mitochondrial superoxide
      level in gestational diabetic rats].
AB  - Objective: To investigate the effects of nicotinamide (NAM) on blood glucose
      level and anti-oxidative enzyme activity in gestational diabetic (GDM) rats.
      Methods: GDM model was induced by injection of STZ (35 mg/kg) in pregnant female
      Sprague-Dawley rats. Nicotinamide was given to GDM rats by gavage at 50, 100 or
      200 mg/kg q.d from gestational d 6 to d 20. The rats were divided into normal
      control group, GDM group (0 mg/kg), low-dose NAM group (50 mg/kg), middle-dose
      NAM group (100 mg/kg) and high-dose NAM group (200 mg/kg) with 8 animals in each
      group. When rats were sacrificed at d 21, the blood glucose level was measured;
      skeletal muscle and fetal brain samples were collected. The expression and
      activity of anti-oxidative enzymes, including superoxide dismutase (SOD1, SOD2),
      catalase (CAT) and sirtuin-3 (SIRT3) were measured by RT-PCR and Western blot.
      Results: Nicotinamide significantly lowered the blood glucose in GDM rats and
      decreased mitochondrial superoxide level in the fetal cortical neurons. SOD2 was
      induced in skeletal muscle by nicotinamide in GDM rats (P<0.05), while no
      significant change was observed in the expression of CAT (P>0.05). Nicotinamide
      increased SIRT3 expression (P<0.05) and decreased deacetylation of SOD2 in
      skeletal muscle of GDM rats (P<0.05). Conclusion: Nicotinamide can lower the
      blood glucose level in GDM rats, and decrease mitochondrial superoxide level,
      which is associated with promoting SIRT3 activity to deacetylate SOD2 and elevate
      SOD2 activity in GDM rats.

PMID- 28752711
TI  - [Establishment of mouse endometrial injury model by curettage or coagulation].
AB  - Objective: To establish mouse endometrial injury model by curettage or
      coagulation. Methods: Female ICR mice were randomly allocated into 2 groups: in
      curettage group, a blunt 20G needle was inserted in one uterine horn with 0.05
      megapascals negative pressure; in coagulation group, one uterine horn was
      coagulated using a monopolar electric needle with 0.5 watts power. In both groups
      the contra-lateral uterine horn was used as control. The morphological changes
      and thickness of endometrium were evaluated 1 week after operation. The
      endometrial samples were taken on d4 of pregnancy, and the expressions of
      endometrial receptivity-related cytokines were examined. The number of implanted
      embryos on each side of uterus was calculated on d10 of pregnancy. Results: There
      was no difference in operation time between 2 groups. In both groups, the
      endometrial glands and stroma were significantly reduced, and the endometrial
      thickness was also significantly decreased on injury side compared to contra
      lateral horn. However, local injury was more severe in coagulation group, uterine
      obliteration and hydrops were developed in 2 mice of coagulation group, and none
      in curettage group. The expressions of leukemia inhibitory factor (LIF) and
      oncostatin M (OSM) were significantly reduced on injured side in both groups
      compared to opposite side; however, the expression of LIF and OSM in curettage
      group was higher than that in coagulation group. The numbers of implanted embryos
      were decreased in both groups on injured side compared to opposite side, and
      fetal death was only observed in coagulation group. Conclusion: Both curettage
      and coagulation can make injury on mouse endometrium, impair endometrial
      receptivity and reduce fertility. Curettage can cause moderate injury, and
      coagulation may lead to more severe injury.

PMID- 28752712
TI  - [Effect of diammonium glycyrrhizinate and phospholipids complex oninflammatory
      gene expression induced by palmitic acid].
AB  - Objective: To investigate the effect of glycyrrhizinate and phospholipids (DGPL)
      complex on inflammatory gene expression in cell inflammation model induced by
      palmitic acid (PA). Methods: Huh7 cells were divided into control, PA and PA+DGPL
      groups. For control group, cells were treated with BSA; for PA group, cells were
      incubated with 0.2 mmol/L saturated fatty acid PA, PA+DGPL group was given 20
      MUmol/L or 100 MUmol/L DGPL in addition to 0.2 MUmol/L PA. After 24 h, the
      expression of inflammation-related genes COX-2 and iNOS and endoplasmic reticulum
      (ER) stress-related gene GRP78 was determined by RT PCR. Oil red staining was
      conducted to observe the effect of DGLP on steatosis. Results: Compared with
      control group, the expression of COX-2, iNOS and GRP78 in PA group was enhanced
      to 6.07+/-0.73(P<0.05), 3.18+/-0.91 (P<0.01) and 3.21+/-1.00(P<0.05),
      respectively. Compared to control group, the expression of COX-2,iNOS and GRP78
      in 100 MUmol/L DGPL group was reduced to 2.40+/-0.76, 1.60+/-0.49 and 1.17 +/
      0.42 (P<0.05); and 20 MUmol DGPL had similar inhibition effect on COX-2 and iNOS
      elevation induced by PA (P<0.01, P<0.05 respectively). In addition, DGLP enhances
      the steatosis of Huh7 cells as demonstrated by oil red staining. Conclusion: PA
      can induce the up-regulated expression of inflammation associated genes COX-2,
      iNOS and ER stress-associated gene GRP78 in Huh7 cells. DGPL is able to protect
      Huh7 cells from PA induced inflammatory gene expression and the beneficial effect
      may be partially due to its unsaturated phospholipid component, which may improve
      ER stress and enhance steatosis.

PMID- 28752713
TI  - [Midpalatal cortex osteotomy assisted rapid maxillary expansion for correction of
      maxillary transverse deficiency in young adults].
AB  - Objective: To evaluate the application of midpalatal cortex osteotomy assisted
      rapid maxillary expansion for correction of maxillary transverse deficiency in
      young adults. Methods: Fourteen young adult patients with maxillary transverse
      deficiency were treated with midpalatal cortex osteotomy assisted rapid maxillary
      expansion. Lateral cephalogram and cone beam CT (CBCT) were taken before and 3
      months after treatment. The width of basal bone, arch of maxilla and the torque
      of anchorage teeth were compared before and after treatment. Results: The width
      of dental arch of maxilla was increased from 40.54+/-5.26 mm before treatment to
      46.83+/-5.83 mm after treatment (P<0.05) and the width of basal bone was
      increased from 64.86+/-4.16 mm to 67.60+/-4.66 mm (P<0.05) at the plane of the
      maxillary first molars. Accordingly, the width of dental arch of maxilla was
      increased from 31.92+/-2.55 mm to 38.65+/-3.14 mm (P<0.05) and the width of basal
      bone was increased from 43.33+/-3.70 mm to 45.78+/-4.57 mm (P<0.05) at the plane
      of first premolar. And the torque of maxillary anchorage teeth were increased
      (P<0.05). Conclusion: Midpalatal cortex osteotomy assisted rapid maxillary
      expansion is an effective micro-invasive method in expansion of basal bone and
      arch of maxilla for young adult patients with maxillary transverse deficiency.

PMID- 28752714
TI  - [Report of two cases of primary mediastinal tuberculosis].
AB  - Two cases of primary mediastinal lymphonode tuberculosis involved right bronchus
      were summarized in the report. Major clinical symptoms included cough and bloody
      sputum. Chest enhanced CT scan showed mediastinal lymph node enlargement with
      ring-shaped enhancement. Bronchoscopy suggested neoplasm in right bronchus.
      Diagnosis of tuberculosis was confirmed by histopathology in samples from lymph
      node puncture and brochoscopic biopsy. The clinical symptoms and medical imaging
      of patients were improved after transbrochoscopic interventional therapy and
      systemic chemotherapy.

PMID- 28752715
TI  - [Advances in application of adoptive T-cell therapy for cancer patients].
AB  - Adoptive T-cell therapy is the administration of tumor cytotoxic T-cells derived
      from either patient himself or donors, which were induced or genetically
      engineered and expanded in vitro, and then injected into patients. Several
      strategies for adoptive T-cell therapy have been developed since last 30 years.
      From lymphokine-activated killer cells, tumor-infiltrating lymphocytes, cytokine
      induced killer cells, to gene-modified T-cells and tumor associated antigen (TAA)
      specific cytotoxic T-cells, the adoptive T-cell therapy has been moving forward
      to more precise tumor targeting and more effective in elimination of cancer
      cells. This article reviewed the advances of therapeutic approaches of adoptive T
      cell therapy for cancer patients.

PMID- 28752716
TI  - [Progress on mechanisms for pathogensto evade NOD-like receptor and Toll-like
      receptor signaling pathways].
AB  - The innate immune system provides a first line of defense against invading
      pathogens, in which the pattern recognition receptors (PRR) recognize pathogen
      associated molecular patterns (PAMP) and initiate the downstream signaling
      pathways to eliminate the encountered pathogens. There are two main classes of
      such signaling pathways: NOD-like receptor (NLR) signaling pathway and Toll-like
      receptor (TLR) signaling pathway. The microbial pathogens under selective
      pressure have evolved numerous mechanisms to avoid and/or manipulate the NLR and
      TLR signal transduction for survival and replication. To evade the NLR signaling
      pathway, pathogens interfere and/or inhibit inflammasome activation in innate
      immune cells by producing virulence factors or reducing PAMPs expression. The
      mechanisms for pathogens to evade TLR signaling pathway include: inhibition of
      mitogen activated protein kinases (MAPKs) cascade reaction, inhibition of NF-KB
      activation, and interference of down-stream signal transduction by producing
      Toll/interleukin-1 receptor (TIR)-containing proteins which bind directly with
      TLRs or adaptor proteins in the signaling pathway.

PMID- 28752717
TI  - Justification for IgE as a therapeutic target in chronic spontaneous urticaria.
AB  - Summary: Monoclonal anti-IgE antibodies (omalizumab) are able to induce
      clinically significant benefits in patients with severe chronic spontaneous
      urticaria (CS). Those results led clinicians and investigators to reconsider a
      possible pathogenic role not previously supported for IgE and its receptors in
      this disease, and to investigate additional approaches for understanding its
      pathogenesis. IgE antibodies to unknown environmental allergens able to trigger
      chronic urticaria are not generally regarded as the etiologic factor for the
      disease. Other proposed mechanisms for the production of wheals and angioedema in
      CSU include IgG autoantibodies and CD4-positive T cells directed to the high
      affinity IgE receptor, autoantibodies to IgE itself, IgE autoantibodies directed
      to thyroid and nuclear autoantigens, highly cytokinergic IgE, and histamine
      releasing factors able to bind to IgE and cause mast cell activation. It is
      expected that a better knowledge on the mechanisms leading to CSU and the
      clarification of the immunological effects of anti-IgE will provide novel
      therapies for this frequent condition.

PMID- 28752718
TI  - Histamine release positive test associates with disease remission in chronic
      spontaneous urticaria: a proof-of-concept study.
AB  - Summary: Background. Histamine release (HR) test has previously been shown to
      predict the presence of endogenous histamine-releasing factors in chronic
      spontaneous urticaria (CSU). Objectives and methods. Twenty CSU patients
      unresponsive to antihistamine treatment were enrolled in order to evaluate the
      correlations between HR test results and demographic features, quality of life,
      disease activity, clinical course, and autologous serum and plasma skin tests
      (ASST and APST). Results. All patients with positive HR test (9/9, 100%) had a
      more severe disease activity at onset (urticaria activity score, UAS > 2) when
      compared to negative HR test patients (5/11; p = 0.04). Quality of life
      questionnaire's results were not substantially different between HR positive and
      negative subgroups at baseline (p > 0.05), and results of HR test and ASST/APST
      did not co-segregate (p > 0.05). After 12 months, patients with a positive HR
      test had a significant reduction of disease activity (p = 0.003) whereas patients
      with a negative HR test did not (p > 0.05), leading to disease remission and
      antihistamine treatment withdrawal in 67% (6/9) of positive HR test patients
      versus 18% (2/11) of negative HR test patients (p = 0.027). Conclusions. Positive
      HR test may predict spontaneous CSU remission at 12 months.

PMID- 28752719
TI  - Serum estradiol concentration, estradiol-to-progesterone ratio and sputum IL-5
      and IL-8 concentrations are increased in luteal phase of the menstrual cycle in
      perimenstrual asthma patients.
AB  - Summary: Background. The results of the research on perimenstrual asthma (PMA)
      pathophysiology are inconsistent, and the role of sex hormones remains
      inconclusive. The aim of the study was to evaluate the influence of serum sex
      steroid (and other) hormones concentrations on lower airway inflammation of PMA
      patients. Methods. Thirty-three women of childbearing age diagnosed as: PMA (n =
      13), non-PMA asthmatics (n = 10), and healthy controls (n = 10) were
      prospectively followed for 12 weeks over 2 consecutive menstrual cycles. On the
      10th and 26th day of each cycle serum 17beta-estradiol, progesterone,
      testosterone, androstendion, dehydroepiandrosteron, cortisol, thyroid-stimulating
      hormone and prolactin were measured, and sputum was induced. Sputum inflammatory
      cell count and IL-5, -6, -8, -10 concentrations were determined. Results. When
      compared to non-PMA asthmatics, the luteal phase of the cycle in PMA subjects was
      associated with increased serum estradiol concentration, estradiol-to
      progesterone ratio (p < 0.001, p = 0.001, respectively) and sputum IL-5 and IL-8
      concentrations (p = 0.045, p = 0.039, respectively). Decreased serum testosterone
      levels (p < 0.05) and a trend to increased serum prolactin levels in both phases
      of the menstrual cycle in PMA subjects were observed. Sputum analysis in PMA
      patients revealed increased total inflammatory cell count in both phases of the
      menstrual cycle (p < 0.05), when compared to non-PMA asthmatics. Conclusions. The
      luteal phase of the cycle in PMA patients is associated with increased serum
      estradiol levels with concurrent higher sputum concentration of IL-5 and IL-8.
      Serum testosterone levels are decreased, and total number of sputum inflammatory
      cells is increased in PMA patients in both phases of the menstrual cycle.

PMID- 28752720
TI  - Effects of omalizumab treatment on serum cytokine concentrations of atopic
      patients with chronic spontaneous urticaria: a preliminary report.
AB  - Summary: Omalizumab has recently obtained indication for chronic spontaneous
      urticaria both in the US and Europe. However, the mechanism of action of this
      drug has yet to be fully elucidated. Previous studies have shown elevations in
      cytokine serum levels in patients with chronic spontaneous urticaria, and it is
      not known whether omalizumab treatment may affect cytokine serum levels in this
      condition. Besides, a proportion of chronic spontaneous urticaria patients have
      concomitant atopy, which may be associated, at least in theory, with prevalence
      of serum Th2-type cytokines. In this study, serial serum samples from five
      patients (4 atopic and 1 nonatopic) with chronic spontaneous urticaria were
      assayed for cytokine concentrations by means of flow-cytometry-based multiplex
      bead assays, before and during omalizumab treatment. Omalizumab appeared to
      significantly affect the concentrations of multiple cytokines in a case of
      severe, long-lasting chronic spontaneous urticaria. Interestingly, IL-22 serum
      levels were found to progressively increase in three of five patients. Further
      studies are thus needed in larger patient populations, to conclusively establish
      whether the mechanism of action of omalizumab in chronic spontaneous urticaria
      also includes modulation of cytokine synthesis.

PMID- 28752721
TI  - Phleum pratense molecular pattern across Italy.
AB  - Summary: Introduction. Phleum pratense (Timothy grass) is the most frequent cause
      of grass allergy in Europe. Molecular-based allergy diagnostics have been
      recently introduced in the clinical practice, allowing to define and characterize
      exactly the sensitization profile. Aim of the study. The present study was aimed
      to investigate the possible relationships between Graminaceae pollen data and the
      pattern of IgE reactivity to different allergen components across Italy. Methods.
      Pollen data, including duration and quantity, were recorded over a 10-year period
      in 24 Italian centres located along the Italian peninsula. Phl p molecular
      patterns (Phl p 1, 5, 7, 12) were evaluated in 4 different Italian geographical
      areas. Results. There were significant differences about pollen count and
      sensitization prevalence across Italy. Different molecular patterns were defined
      considering the different Italian locations. Conclusion. This study demonstrates
      that Phleum pratense sensitization is relevant in Italy, but there are
      significant geographical variations variations as far as pollen exposure and
      pattern of IgE reactivity to the considered allergen components are concerned.
      This information may have clinical relevance in managing patients allergic to
      grass pollen.

PMID- 28752722
TI  - Effects of food allergy on the dietary habits and intake of primary schools'
      Cypriot children.
AB  - Summary: Aim. To determine whether food allergy affects overall dietary intake
      and food choices in Cypriot primary school children. Methods. As part of the
      first epidemiological study in Cyprus on food allergy in primary school children,
      two 24-hour recalls (one from a week and one from a weekend day) of twenty-eight
      food allergic children (21 girls) and thirty healthy children (20 girls) aged 6
      11 years old, were analysed and compared regarding their macro- and micronutrient
      content, food choices and meal distribution. Results. Significant differences
      between the two subgroups of children were estimated regarding the total energy
      intake and macronutrients, where food allergic children were found to consume in
      lower quantities, as well as for calcium, niacin, fiber and vitamin E. Food
      allergic children were also found to avoid combining foods from the various food
      groups in their meals, and to prefer specific food products from each category,
      whereas they consumed higher amounts of sugar and fructose. Conclusion. Food
      allergy in Cypriot food allergic children impacts on both the quality and
      quantity of food choices, probably due to lack of nutritional education regarding
      proper elimination diet and alternative nutrient sources.

PMID- 28752723
TI  - Red meat allergy induced by tick bites: A Norwegian case report.
AB  - Summary: Food allergies, especially delayed hypersensitivity reactions, are often
      challenging for both patients and clinicians. Here, we report the case of a 64
      year-old man who had allergic reactions six hours after eating a meal containing
      red meat. He reported that he had several tick bites in months before the
      reaction. High serum specific IgE levels of alpha-gal confirmed the diagnosis of
      alpha-gal allergic reaction with delayed onset after red meat ingestion caused by
      tick bite.

PMID- 28752724
TI  - CRP, D-dimer, fibrinogen and ESR as predictive markers of response to standard
      doses of levocetirizine in patients with chronic spontaneous urticaria.
AB  - Summary: According to current guidelines, non-sedative H1-antihistamines (nsAH)
      are the first-line therapy of chronic spontaneous urticaria (CSU). But even up
      dosed antihistamines (to four times the standard dose) produce symptom resolution
      in less than 50% of patients. Biomarkers that can predict the response to nsAH
      are still unknown. We carried out a prospective study and used discriminant
      analysis to evaluate the combination of D-dimer, fibrinogen, C-reactive protein
      and ESR values for predicting the outcome of treatment with levocetirizine in 84
      CSU patients. We found that elevation of these parameters is associated with more
      active disease, low quality of life and lack of response to standard doses of
      levocetirizine. Thus, evaluation of these markers may be considered useful before
      starting treatment with nsAH. The mechanisms behind the increase in these
      parameters in CSU patients need to be elucidated in further studies.

PMID- 28752725
TI  - Optional caval filter in kidney cancer patients with tumor thrombus level I and
      II.
AB  - BACKGROUND: Kidney diseases requiring a radical surgical approach can come up
      complicated by the presence of a thrombus of the renal vein or the inferior vena
      cava (IVC). The overwhelming majority of these cases concern the presence of a
      kidney tumor, especially renal cell carcinoma (RCC). Kidney tumor presenting with
      thrombus extension into the IVC represents a difficult operative challenge,
      especially for the risk of thrombus dislocation due to the manipulation of the
      IVC during tumor isolation, which may result in pulmonary embolism (PE). METHODS:
      We propose a retrospective cohort study regarding 10 patients (thrombus level I
      or II) operated in our center from 2010 to 2015. All of them had a renal tumor.
      In 8 patients TC proved tumor thrombus extended into the IVC<2 cm above the renal
      vein (level I), in the remaining patients the thrombus entered the IVC>2 cm above
      the renal vein but below the hepatic veins (level 2). All the patients underwent
      an IVC temporary/optional filter placement as a preoperative maneuver before
      radical nephrectomy. RESULTS: The efficacy of the procedure is confirmed by the
      absence of any inter- or postsurgical thromboembolic event in all patients;
      filter was removed in 3 patients, moreover, concerning the long-term information
      we obtained about the patients, none of them has showed complete occlusion of
      IVC. CONCLUSIONS: The results of the study support effectiveness of preoperative
      temporary IVC placement to prevent thrombosis embolism shedding and to improve
      surgical safety.

PMID- 28752726
TI  - In-vitro maturation in women with polycystic ovaries and high anti-Mullerian
      hormone levels.

PMID- 28752727
TI  - Assessment of left atrial function in patients with hypertrophic cardiomyopathy
      using two-dimensional strain: a comparison with volume-derived values.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common heart disease. Left
      atrial (LA) function plays an important role in the diastolic function in
      patients with HCM. In this study, two-dimensional speckle tracking imaging (2D
      STI) was used to assess left atrial (LA) function in patients with HCM. METHODS:
      Thirty-four patients with HCM and thirty-four age- and gender-matched normal
      subjects were studied. The LA Volume-Derived Index was measured using 2D
      ultrasonic images. The LA strain (S-reservoir, S-conduit, S-booster pump) and the
      strain rate (SR-reservoir, SR-conduit, SR-booster pump), representing the
      reservoir, conduit and booster pump functions, respectively, were measured.
      RESULTS: The LA reservoir, conduit and booster pump functions were significantly
      different between patients with HCM and normal subjects. The values in patients
      with HCM were less than those in normal subjects. In patients with HCM, S
      reservoir and SR-reservoir were significantly correlated with the total LA
      ejection fraction (LAEF), LA Expansion Index and left ventricular (LV) global
      longitudinal strain. S-conduit and SR-conduit were significantly correlated with
      e' and LV global longitudinal strain. S-booster pump and SR-booster pump were
      significantly correlated with the A, a', active LAEF and LA Expansion Index. S
      booster pump was significantly correlated with the LV global longitudinal strain.
      CONCLUSIONS: 2D-STI conveniently demonstrated the LA dysfunction in patients with
      HCM by detecting the LA strain and strain rate. The accurate assessment of LA
      function could have potential clinical value for the treatment of patients with
      HCM.

PMID- 28752728
TI  - Evaluation of On-Clopidogrel platelet reactivity overtime, SYNTAX SCORE, genetic
      polymorphisms and their relationship to one year clinical outcomes in STEMI
      patients undergoing PCI.
AB  - BACKGROUND: The aim of this paper was to investigate the variability of On
      clopidogrel platelet reactivity overtime, the association between HTPR, gene
      polymorphism and Syntax Score (SS) for risk prediction of MACE in patients with
      ST-Elevation Myocardial Infarction (STEMI) undergoing percutaneous coronary
      intervention (PCI). Platelet function testing may be used to optimize
      antiplatelet therapy in high-risk patients, but identification of this subset of
      patients remains a challenge. High on-treatment platelet reactivity (HTPR) has
      emerged as a risk factor for major adverse cardiovascular events (MACE). Genetic
      polymorphisms play key role in clopidogrel hypo-responsiveness. METHODS: This
      prospective, observational study includes 151 consecutive STEMI patients who
      underwent PCI and treated with clopidogrel. Platelet Activity Index (PAI) was
      measured at two different time points post-PCI. Patients were stratified by the
      presence of HTPR (PAI>=5) and by upper SS (SS>=15). Allele-specific polymerase
      chain reaction for identifying CYP2C19*2, CYP3A5*3, PON1, P2Y12 gene
      polymorphisms was done. The end point at one year follow up was MACE. RESULTS:
      There was a significant increase in mean platelet reactivity and the total number
      of non-responders over a period of three months (9.9% vs. 23.8% P=0.05). Patients
      with SS>=15 in the presence of HTPR during follow-up had highest rates of MACE,
      especially among diabetics compared to non-diabetics (P=0.024). The prevalence of
      CYP2C19*2 polymorphism was 49%%, was associated with HTPR during follow-up but
      unassociated with MACE. CONCLUSIONS: In STEMI patients undergoing PCI, the
      presence of SS>=15, HTPR during follow-up were associated with high MACE rates
      especially among diabetics. Hence, such high-risk groups shall require sequential
      testing for HTPR and optimize therapy accordingly.

PMID- 28752729
TI  - Cardiac imaging in patients with cardiac syncope.
AB  - Syncope is a common symptom with a possibly unfavorable prognosis, especially
      when the cause is a cardiac disease. Often diagnostic workup requires multiple
      and challenging investigations to determine whether the patient has a structural
      heart disease. Cardiac imaging tests should be used when baseline clinical
      findings raise the suspicion of a cardiac syncope. Transthoracic echocardiography
      is the first line imaging examination as it helps establish the cause of syncope
      and supplies useful information for prognostic stratification by evaluating
      systolic ventricle function. Advanced imaging techniques such as multidetector
      computed tomography and cardiac magnetic resonance imaging should be reserved for
      selected cases when echocardiography is inconclusive. With this review we aim to
      report the main information obtainable with cardiac imaging tests in patients
      with suspected or known cardiac syncope. We summarize the most common as well as
      rarer heart structural diseases which may cause syncope and briefly state the
      possible physio-pathologic mechanism. For each heart disease we describe the role
      of the various imaging techniques and the possible diagnostic and prognostic
      information provided by these techniques.

PMID- 28752730
TI  - Edge effect after intracoronary beta radiation brachytherapy and bare metal stent
      implantation: the pathway for very late stent failure.

PMID- 28752731
TI  - Cardiac imaging in patients with dyspnea.
AB  - Acute dyspnea is a frequent cause of access to the Emergency Department.
      Differentiation between cardiogenic and respiratory causes does not always seem
      simple and certain, causing a delay in initiating targeted therapies and
      prolonging the patient's stay in the emergency department. The basic elements for
      the diagnosis remain the history and the objective examination, supplemented by
      the execution of an electrocardiogram, a determination of blood parameters and
      the execution of a chest X-ray. The limits of radiological semeiotics, related to
      a low sensitivity to high specificity, promote other methods available to the
      first aid physician. Specifically, the determination of the natriuretic B-type
      peptide and transthoracic ultrasound is proposed as a method, recognized and
      validated by the recent letter on the patient bed, relatively easy to execute,
      fast learning, fast execution and non-invasive (referring to "ultrasound"). The
      sensitivity and specificity of both methods are high (86.7% and 93%,
      respectively) in the diagnosis of alveolus-interstitial syndrome, simplifying and
      accelerating the differential diagnosis of acute dyspnea.

PMID- 28752732
TI  - Echocardiographic methods integrated in the context of multimodality imaging.

PMID- 28752733
TI  - Pediatric mesenchymal stromal cells therapy: an update.
AB  - The mesenchymal have heterogeneous composition and till date no single,
      definitive marker for their identification is available. Further, this cell
      population is identified by their adherence to plastic, spindle-like morphology
      and their trilineage plasticity. They also have ability to differentiate into
      bone, cartilage and fat. Moreover, MSC as "multipotent stromal cells" is a
      preferred choice over "mesenchymal stem cells", as the later definition includes
      many cell populations, several of which do not fulfill the self-renewal and multi
      lineage potential of true stem cells. So, the present review article is focused
      to enlighten recent views of MSC therapy in the field of Pediatrics.

PMID- 28752734
TI  - Elevated baseline adiponectin level predicting an increased risk of disease
      activity in idiopathic nephrotic syndrome and chronic kidney disease in children.
AB  - BACKGROUND: Adiponectin, an adipocyte-derived protein, is present abundantly in
      circulation and has anti-atherogenic and anti-inflammatory effects, so we aimed
      to assess the role of adiponectin in idiopathic nephrotic syndrome and chronic
      kidney disease in children. METHODS: Overall of 290 children, 95 patients with
      the steroid-responsive idiopathic nephrotic syndrome (50 in remission and 45 in
      relapse).Another 95 patients with chronic kidney disease (50 on hemodialysis and
      45 on conservative therapies) and 100 apparently healthy matched children were
      enrolled into the study. Serum adiponectin levels, blood chemistry
      (protein/albumin, serum creatinine, blood urea and electrolytes levels) and 24
      hour proteinuria w studied as well. RESULTS: There was highly significant
      increasing differences in adiponectin level between the relapsed idiopathic
      nephrotic syndrome (26.93+/- 6.79 MUg/mL) compared to remission (10.96+/- 3.33
      MUg/mL) and control group (4.89+/- 1.01 MUg/mL) and between remission in
      comparing to control group (P <0.001). Also there was significant negative
      correlation between adiponectin level and serum albumin level in the relapse
      group (r=- 0.60, P=<0.05), and highly positive correlation between adiponectin
      level and 24-hour proteinuria in relapse (r=0.98, p= <0.001) and remission group
      (r= 0.92, P = <0.001). Regarding children with chronic kidney disease, There were
      high significant increasing differences in adiponectin levels in conservative
      (13.88 +/- 4.27 MUg/mL) and dialysis (15.09 +/- 6.14 MUg/mL) groups compared to
      controls (6.05 +/- 5.83 MUg/mL) with P <0.001. Furthermore, there was a
      significant positive correlation between adiponectin and serum creatinine &blood
      urea levels in both conservative and dialysis groups with P <0.05. CONCLUSIONS:
      Adiponectin can be considered as an important useful biomarker for chronic kidney
      diseases in children.

PMID- 28752735
TI  - The most-cited articles in pediatric imaging: a bibliometric analysis.
AB  - BACKGROUND: The number of citations that an article has received reflects its
      impact on the scientific community. The purpose of our study was to identify and
      characterize the 51 most-cited articles in pediatric imaging. METHODS: Based on
      the database of Journal Citation Reports, we selected 350 journals that were
      considered as potential outlets for pediatric imaging articles. The Web of
      Science search tools were used to identify the most-cited articles relevant to
      pediatric imaging within the selected journals. RESULTS: The 51 most-cited
      articles in pediatric imaging were published between 1952 and 2011, with 1980-
      1989 and 2000-2009 producing 15 articles, each. The number of citations ranged
      from 576-124 and the number of annual citations ranged from 49.05-2.56. The
      majority of articles were published in pediatric and related journals (n=26),
      originated in the United States (n=23), were original articles (n=45), used MRI
      as imaging modality (n=27), and were concerned with the subspecialty of brain
      (n=34). University College London School of Medicine (n=6) and School of Medicine
      University of California (n=4) were the leading institutions and Reynolds EO
      (n=7) was the most voluminous author. CONCLUSIONS: Our study presents a detailed
      list and an analysis of the most-cited articles in the field of pediatric
      imaging, which provides an insight into historical developments and allows for
      recognition of the important advances in this field.

PMID- 28752736
TI  - Influence of skin disinfection prior removal of perineural catheter on bacterial
      colonization, contamination and local inflammation: a prospective randomized
      study.
AB  - BACKGROUND: There is a wide variation of perineural catheter (PNC) colonization
      rates in the literature. The impact of skin disinfection on PNC colonization and
      inflammation is not clear. The objective of this prospective, randomized clinical
      study was to investigate the influence of alcoholic skin disinfection before PNC
      removal on the detection of bacteria on PNC. METHODS: Two hundred patients
      receiving a PNC for orthopedic surgery were randomized to receive (with-group) or
      not (without-group) a skin disinfection with a sprayed alcoholic solution before
      removal of the PNC. Bacterial colonization and contamination of the PNC and
      clinical signs of inflammation and infection of the PNC insertion site were
      evaluated. Skin disinfection with a sprayed alcoholic solution and sterile
      removal of the distal and subcutaneous part of the PNC was performed after 72
      hours or earlier if signs of infection occurred with semiquantitative culture and
      enrichment culture of both parts. RESULTS: Alcoholic skin disinfection before PNC
      removal significantly reduced bacterial colonization with a reduction from 28% to
      14% and from 32% to 17% for the tip and the subcutaneous part of the PNC,
      respectively (P<0.05). Clinical signs of inflammation at the PNC insertion site
      were similar (73%) in the two groups. The detection of colonization in 54 (27%)
      out of 200 PNC did not correlate with clinical signs of inflammation
      independently of the number of bacteria isolated. Redness was noted in 71% and
      68% of patients in the without- and with-alcoholic skin disinfection-group
      respectively. Local pain on pressure was present in 28% and 19% in the without-
      and with-group respectively. CONCLUSIONS: Alcoholic skin disinfection before PNC
      removal reduced the detection of PNC colonisation by 50%. There was no
      correlation between clinical signs of inflammation and PNC colonization.

PMID- 28752737
TI  - Serratus anterior plane block for right minithoracotomy revision after mitral
      valve repair.

PMID- 28752738
TI  - Veno-arterial extracorporeal membrane oxygenation as an intraoperative rescue
      option in case of portopulmonary hypertension recognized during liver
      transplantation.

PMID- 28752739
TI  - Trends in Health Behaviour in Czech School-aged Children: HBSC Study. Preface.
AB  - The Health Behaviour in School-aged Children (HBSC) study is now in its 34th
      year. It continues to grow not only as a source of reliable and valid data on the
      health behaviours of 11-, 13- and 15-year-olds, but also regarding its membership
      - 46 countries and regions across Europe and North America are now included. The
      HBSC study is a cohort cross-sectional questionnaire-based study focusing on
      health and health-related behaviours in adolescents in the context of their
      social environment. This age was selected because of the significant cognitive,
      psychological, and biological processes taking place in this period of the
      lifespan, as well as because of the fact that health-related behaviours adopted
      at this age are known to persist into adulthood. The findings from the HBSC study
      are used to monitor health, well-being, and health-related behaviours in school
      aged children; deepen the understanding of the social determinants of health; and
      provide evidence-based data for policy makers and practitioners aiming to improve
      the lives of young people.

PMID- 28752740
TI  - Methodological Aspects of Trend Studies and Development of the HBSC Study in the
      Czech Republic.
AB  - The aim of the study is to present the theoretical background of trend studies in
      general, to characterize the international Health Behaviour in School-aged
      Children (HBSC) study and to describe its methodology and changes of the Czech
      HBSC study between 1994 and 2014. The first part describes various types of trend
      research studies including their advantages and disadvantages. The second part
      summarizes the history of the HBSC study in an international context and
      particularly in the Czech Republic. The final part presents the basic
      methodological data from six surveys conducted in the Czech Republic between 1994
      and 2014.

PMID- 28752741
TI  - Trends in Overweight and Obesity in Czech Schoolchildren from 1998 to 2014.
AB  - OBJECTIVE: Overweight and obesity in adolescents is associated with many health
      risks and considerable direct and indirect healthcare costs. The purpose of this
      study is to examine trends in the prevalence of overweight and obesity in 11-, 13
      and 15-year-old adolescents in the Czech Republic from 1998 to 2014. METHODS:
      Data from five self-reported survey rounds (1998, 2002, 2006, 2010, and 2014) of
      the Health Behaviour in School-aged Children Study (HBSC) were used to assess
      trends in overweight and obesity among Czech adolescents. The total sample
      consisted of 19,103 adolescents (51.2% girls). A logistic regression analysis was
      used to assess trends in different age and gender categories. RESULTS: From 1998
      to 2014 a significant increase in the prevalence of overweight and obesity was
      observed among boys in all age categories (11 years old 22.2%1998- 28.3%2014; 13
      years old 17.9%1998- 26.7%2014; 15 years old 9.8%1998- 20.8%2014) and among 15
      year-old girls (6.0%1998- 10.9%2014). None of the age and gender categories
      showed an overall decrease over the 16-year period. In boys, the prevalence of
      overweight was significantly higher with steeper negative trends compared with
      girls. However, stabilization in overweight rates was observed between 2010 and
      2014 in all age and gender groups. CONCLUSION: Nationally representative self
      reported data show a significant increase in overweight (including obesity)
      prevalence among children from 1998 to 2014 in the Czech Republic. The results
      also suggest stabilization in overweight prevalence between 2010 and 2014.
      Continuing research is needed to determine future trends while interventions
      aimed at reducing overweight and obesity in children should be implemented on
      different levels of public policy.

PMID- 28752742
TI  - Trends in Screen Time Behaviours in Czech Schoolchildren between 2002 and 2014:
      HBSC Study.
AB  - OBJECTIVE: Screen-based behaviours such as watching television or computer use
      are among the most prevalent sedentary behaviours adolescents spend time on.
      There is a lack of recent estimates on prevalence and changes in the amount of
      time spent on screen-based behaviour across Central and Eastern Europe. The main
      aim is to assess the trends in the prevalence of current recommendations for the
      screen time (<=2 hours per day) of school-aged children in the Czech Republic
      between 2002 and 2014. METHODS: We used an internationally established
      methodology based on the Health Behaviour in School-aged Children (HSBC) study.
      Data was derived from Czech national representative samples of 11-, 13- and 15
      year-olds collected in the years 2002 (N=4,065), 2006 (N=4,170), 2010 (N=3,962)
      and 2014 (N=4,338). RESULTS: The results indicated that the boys and girl
      surveyed in 2014 are up to two times more likely to meet the current
      recommendations for watching television in comparison with groups of
      schoolchildren of the same age surveyed in 2002. In contrast, computer use by
      adolescents increased markedly between 2006 and 2014. Taking total screen time
      into account, spending two hours per day or less on it decreased significantly
      among boys (OR=0.74, 95% CI=0.62-0.89) and girls (OR=0.80, 95% CI=0.70-0.92)
      between 2006 and 2014. CONCLUSIONS: As screen time is an important indicator of
      time spent in a sedentary way, our findings call for more interventions to reduce
      the time that school-aged children spend in front of screens.

PMID- 28752743
TI  - Trends in Active Commuting to School among Czech Schoolchildren from 2006 to
      2014.
AB  - OBJECTIVE: Active commuting (AC) is an important factor in increasing the total
      daily physical activity (PA) in children, which is significant for their health
      and positive physical behaviour in adulthood. The objective of the study was to
      describe trends in active commuting to school among Czech girls and boys aged 11
      15 years from 2006 to 2014, using data from the Health Behaviour in School-aged
      Children (HBSC) study. METHODS: To investigate trends in AC among Czech children
      of school age data obtained from the HBSC surveys carried out in 2006, 2010, and
      2014 was used. The study sample comprised 12,273 respondents, out of whom 5,992
      (48.8%) were boys and 6,281 (51.2%) girls. The overall trends in AC were
      evaluated using logistic regression analysis. RESULTS: Compared with 2006, there
      was an overall decrease in AC among the 13-year-old boys and 13-year-old girls
      (boys - 1.8% in 2006 to 50.1% in 2014, girls - 69.3% in 2006 to 46.3% in 2014).
      The proportion of children AC (walking and cycling) to school significantly
      decreased from 74.3% in 2006 to 53.4% in 2014. CONCLUSION: This study
      demonstrated that AC to school decreased sharply among Czech children of school
      age from 2006 to 2014. However, walking was the most frequently used mode of
      travel. The boys were significantly more likely to cycle to school compared to
      the girls. PA interventions for youth should encourage participation in AC to
      school in the Czech Republic.

PMID- 28752744
TI  - Trends in Perception of Psychosocial School Environment: HBSC Study 2002-2014 in
      the Czech Republic.
AB  - OBJECTIVE: School is a place where students spend most of their daytime hours.
      Previous studies indicate that the class climate significantly affects students
      in both positive and negative ways. The aim of our study is to describe the
      trends in the psychosocial school environment based on four surveyed years in the
      Czech Republic. METHODS: The trends in perception of school were assessed by the
      standardised self-reported HBSC questionnaire from data collected in 2002, 2006,
      2010, and 2014. The overall sample included 8,530 girls and 8,087 boys. Data was
      analysed separately by gender and three age categories 11, 13, and 15 years.
      Trends were calculated using descriptive categories and percentages. To identify
      factors influencing school likeness we used binominal logistic regression.
      RESULTS: Results showed that school satisfaction declines with age both in boys
      and girls in each of four surveyed periods. Students who do not feel a high level
      of support from the teacher are more prone to negative perceptions of school.
      School duties in both genders were perceived to be greater and more stressful in
      2014 than in 2002. CONCLUSIONS: Interventions to support the perception of
      psychosocial school environment via the educational system should, therefore,
      take the aforementioned variation into account.

PMID- 28752745
TI  - National Time Trends in Bullying among Adolescents in the Czech Republic from
      1994 to 2014.
AB  - OBJECTIVE: Bullying in school is a public health concern which continues to be a
      serious threat to physical and emotional health of children and adolescents. The
      purpose of this study is to examine trends in bullying behaviour among school
      aged children in the Czech Republic. METHODS: Data were obtained from cross
      sectional self-report surveys in the years 1994-2014 as a part of the Health
      Behaviour in School-aged Children study (HBSC) from a representative sample of 11
      , 13-, and 15-year olds. RESULTS: The highest proportion of children who bullied
      others (20-47%) occurred during the years 1994 and 1998. The logistic regression
      models showed significant decreasing trends in bullying others and also in being
      bullied, regardless of age and gender. CONCLUSION: The decreasing trend in
      bullying may be the consequence of a preventive policy in the Czech Republic, but
      also a change in the understanding of the concept of bullying in society.

PMID- 28752746
TI  - Trends in Parent-adolescent Communication in the Czech Republic between 2002 and
      2014: Results of the HBSC Study.
AB  - OBJECTIVE: Good parent-child communication is associated with adolescent well
      being. The aim of the present study was to report time trends in parent
      adolescent communication in biological and stepfamilies in the Czech Republic
      between 2002 and 2014 and to assess gender and age differences. METHODS: The
      research sample consisted of 16,160 adolescents aged 11, 13, and 15 years (48.1%
      of boys) who participated in the 2002, 2006, 2010 and 2014 surveys within the
      Health Behaviour in School-aged Children (HBSC) study in the Czech Republic. The
      trends in family communication were evaluated using logistic regression. RESULTS:
      Compared with 2002, a significant increase in the ease of communication with
      biological parents was observed in 2014. On the other hand, the adolescents'
      perception of communication with stepparents did not change in this period.
      Compared with the girls, a higher rate of boys reported communication with their
      father or stepfather as being easy throughout the study period. The ease of
      talking to biological parents decreased with age. CONCLUSION: The growing
      positive trend demonstrated an improvement in communication in intact families at
      the beginning of the 21st century, while communication with stepparents remained
      unchanged from 2002 to 2014. The increase in rates of ease of communication with
      biological fathers was reported by both genders. However, the ease of talking to
      biological mothers grew mainly among boys.

PMID- 28752747
TI  - Trends in Tobacco Smoking among Czech School-aged Children from 1994 to 2014.
AB  - OBJECTIVE: The aim of the article is to examine trends in tobacco consumption
      among the Czech school-age population. METHODS: For the analysis, data from the
      Czech Health Behaviour in School-aged Children project, conducted between 1994
      and 2014 were used. Trends in tobacco smoking were determined separately for boys
      and girls, applying the binary logistic regression with survey period as an
      independent variable for the smoking status. RESULTS: The analysis showed that
      there have been significant changes in adolescent tobacco smoking for the recent
      20 years. While the share of current school-aged smokers was continuously
      increasing since the mid-1990s, the trend reached its peak in the mid-2000s.
      CONCLUSION: In recent years, the prevalence of adolescent smokers has
      significantly declined in the Czech Republic. Despite this recent decline,
      adolescent smoking remains a major challenge for the national health policy.

PMID- 28752748
TI  - Trends in Lifetime Cannabis Use among Czech School-aged Children from 2002 to
      2014.
AB  - OBJECTIVE: The aim of the study was to examine trends in the prevalence of
      lifetime cannabis use among the Czech 15-year old students. METHODS: Data from
      the nationally representative Health Behaviour in School-aged Children Survey,
      conducted in the Czech Republic in 2002, 2006, 2010 and 2014, were used. Trends
      in cannabis use among both boys and girls were modelled through binary logistic
      regression with period as a predictor of the lifetime cannabis use. RESULTS: The
      prevalence of lifetime cannabis use has significantly decreased among young
      Czechs, particularly among boys. Gender differences in cannabis use have been
      also gradually decreasing since 2002, with no significant differences between
      genders in recent period. CONCLUSIONS: Although there are positive changes in the
      prevalence of adolescent cannabis use, from the European perspective, Czech
      students still belong to those with significantly higher rates in this respect.
      Thus, alongside with the use of other substances, adolescent cannabis consumption
      remains an important challenge for the national public health policy.

PMID- 28752749
TI  - Trends in Life Satisfaction and Self-rated Health in Czech School-aged Children:
      HBSC Study.
AB  - OBJECTIVE: The aim of the study is to examine cross-sectional time trends of life
      satisfaction and self-rated health in a representative sample of Czech children
      aged 11, 13 and 15 years using the Health Behaviour in School-aged Children
      (HBSC) study data from the Czech Republic. METHODS: Data from survey years 2002,
      2006, 2010 and 2014 was used. The sample consisted of 16,357 participants (48.5%
      of boys). Life satisfaction (LS) was measured by Cantril's ladder; self-rated
      health was measured through the simple item "Would you say your health is:
      excellent, good, fair, poor". RESULTS: Most of the children were satisfied with
      their lives in all surveyed years (mean LS scores range from 7.21 to 7.51;
      maximum 10). LS was consistently significantly associated (p<0.001) with age and
      gender. Overall, children and adolescents in the Czech Republic also reported
      good health. In total, 87.6% of respondents from all samples reported their
      health as excellent or good. Gender was found to be significantly associated with
      self-rated health (p<0.05) in all surveyed years. CONCLUSIONS: No permanent
      trends in both followed indicators have been seen in the examined period.

PMID- 28752750
TI  - Trends in Children's Toothbrushing in the Czech Republic from 1994 to 2014:
      Results of the HBSC Study.
AB  - OBJECTIVE: Brushing one's teeth twice a day is the main self-care method to
      prevent the most prevalent non-communicable diseases. The aim of the study is to
      describe the trends in brushing teeth in 11-, 13-, and 15-year-old Czech children
      between 1994 and 2014. METHODS: One question about oral health from the HBSC
      study protocol was used in the six surveys (1994, 1998, 2002, 2006, 2010, and
      2014). Altogether, 21,170 answers from boys and girls were analyzed using
      statistical description and binominal logistic regression. RESULTS: The findings
      showed that the prevalence of brushing their teeth more than once a day increased
      throughout the twenty years, more so in boys, but a preventive programme is still
      needed to educate the 21-38% of those who brush their teeth less than twice a
      day. CONCLUSION: Although the recommended frequency of brushing their teeth has
      increased among Czech school-aged children, it still lags far behind the
      recommended twice-a-day regularity, especially among boys.

PMID- 28752751
TI  - Trends in Medically Attended Injuries in Czech Adolescents.
AB  - OBJECTIVE: Due to the importance of surveillance of injuries and accidents in the
      Czech Republic, the purpose of this study was to report the temporal trends of
      injuries of Czech adolescents between 2002 and 2014. METHODS: Adolescents
      (N=20,038) from the Czech Republic, that took part in the 2002, 2006, 2010 and
      2014 HBSC study, reported the frequency of medically attended injuries in the
      past 12 months. Repeated binary logistic regressions with different years as
      reference categories were performed. RESULTS: Less than half (44.7%) of all Czech
      adolescents reported they had experienced at least one medically attended
      injuries in the past 12 months, with boys experiencing more injuries than girls
      (p<0.001), and the injuries were more common in older adolescents. Fewer boys
      reported injury in 2014 when compared to 2002 (OR, CI: 0.81, 0.72-0.90), there
      was also a significant decrease in injuries among girls between 2014 and 2006
      (OR, CI: 0.77, 0.69-0.86). CONCLUSIONS: The trend was not linear amongst boys.
      Along with improved safety promotion education, the rate of injuries decreased
      among adolescents between the years 2002 and 2014.

PMID- 28752752
TI  - Trends in Sexual Behaviour in Czech Schoolchildren between 2002-2014.
AB  - OBJECTIVE: The aim of this study was to report on trends in the prevalence in age
      at first intercourse of Czech schoolchildren and a difference between sexes.
      METHODS: Prevalence in age at first intercourse of Czech schoolchildren was
      observed under the Health Behaviour in School-aged Children study in the years
      2002, 2006, 2010 and 2014. In addition, a random representative sample of
      children attending 9th grade completed the questions related to sexual behaviour.
      A total of 4,804 boys and girls at the age of 15 years were included in the
      study. The chi-square test and analysis of variance were used for data
      assessment. RESULTS: Experience with first sexual intercourse before 15 years was
      confirmed by 16% of boys and 19.4% of girls. Average age of coitarche in both
      sexes most often ranged between 14 and 15 years. Since 2006 boys had
      significantly lower age at coitarche. Only in 2010 the girls had first
      intercourse more frequently than boys. Since 2010 the number of Czech adolescents
      of both sexes having first intercourse before the age of 15 years has
      significantly increased. However, a rise in average age of coitarche over 15
      years in both sexes occurred in 2014. CONCLUSIONS: The number of Czech children
      having a sexual intercourse before 15 years has significantly increased since
      2010.

PMID- 28752753
TI  - Divergent Synthesis of Functionalized Quinolines from Aniline and Two Distinct
      Amino Acids.
AB  - A practicable quinoline synthesis from aniline and two amino acids was developed
      for generating a wide range of quinolines with high efficiency and diversity.
      Thus, it facilitated the creations of pharmaceutical derivatives, photochemical
      active compounds, and challenging scaffolds. The concept of using two amino acids
      as heterocyclic precursors has been raised for the first time. Mechanistic
      studies revealed that I2 enabled decarboxylation, oxidative deamination, and
      selective reconstruction of new C-N and C-C bonds processes.

PMID- 28752754
TI  - One Step Forward for Reducing False Positive and False Negative Compound
      Identifications from Mass Spectrometry Metabolomics Data: New Algorithms for
      Constructing Extracted Ion Chromatograms and Detecting Chromatographic Peaks.
AB  - False positive and false negative peaks detected from extracted ion chromatograms
      (EIC) are an urgent problem with existing software packages that preprocess
      untargeted liquid or gas chromatography-mass spectrometry metabolomics data
      because they can translate downstream into spurious or missing compound
      identifications. We have developed new algorithms that carry out the sequential
      construction of EICs and detection of EIC peaks. We compare the new algorithms to
      two popular software packages XCMS and MZmine 2 and present evidence that these
      new algorithms detect significantly fewer false positives. Regarding the
      detection of compounds known to be present in the data, the new algorithms
      perform at least as well as XCMS and MZmine 2. Furthermore, we present evidence
      that mass tolerance in m/z should be favored rather than mass tolerance in ppm in
      the process of constructing EICs. The mass tolerance parameter plays a critical
      role in the EIC construction process and can have immense impact on the detection
      of EIC peaks.

PMID- 28752755
TI  - Oil-Repellent Antifogging Films with Water-Enabled Functional and Structural
      Healing Ability.
AB  - Healable oil-repellent antifogging films are fabricated by layer-by-layer
      assembly of hyaluronic acid (HA) and branched poly(ethylenimine) (bPEI), followed
      by immersion in the aqueous solutions of perfluorooctanesulfonic acid potassium
      salt (PFOS). The loading of PFOS endows the HA/bPEI films with oil repellency
      while maintaining its original hydrophilicity. The resulting films have an
      excellent antifogging ability, and various organic liquids can easily slide down
      the slightly tilted films (<10 degrees ) without any residue. Through water
      assisted migration of PFOS and polyelectrolytes, oil-repellent antifogging films
      are able to repetitively and autonomously recover their damaged oil repellency
      and transparency caused by plasma etching, cutting, or scratching, prolonging
      their life span. The as-developed healable oil-repellent antifogging films have
      potential application as antifingerprint coatings for touch screens, antigraffiti
      coatings for signs and shop windows, and antifogging coatings for lenses,
      mirrors, and windshields.

PMID- 28752756
TI  - Successful Coupling of a Bis-Amidoxime Uranophile with a Hydrophilic Backbone for
      Selective Uranium Sequestration.
AB  - The amidoxime group (-RNH2NOH) has long been used to extract uranium from
      seawater on account of its high affinity toward uranium. The development of
      tunable sorbent materials for uranium sequestration remains a research priority
      as well as a significant challenge. Herein, we report the design, synthesis, and
      uranium sorption properties of bis-amidoxime-functionalized polymeric materials
      (BAP 1-3). Bifunctional amidoxime monomers were copolymerized with an acrylamide
      cross-linker to obtain bis-amidoxime incorporation as high as 2 mmol g-1 after
      five synthetic steps. The resulting sorbents were able to uptake nearly 600 mg of
      uranium per gram of polymer after 37 days of contact with a seawater simulant
      containing 8 ppm uranium. Moreover, the polymeric materials exhibited low
      vanadium uptake with a maximum capacity of 128 mg of vanadium per gram of
      polymer. This computationally predicted and experimentally realized selectivity
      of uranium over vanadium, nearly 5 to 1 w/w, is one of the highest reported to
      date and represents an advancement in the rational design of sorbent materials
      with high uptake capacity and selectivity.

PMID- 28752757
TI  - Detailed Investigation and Comparison of the XCMS and MZmine 2 Chromatogram
      Construction and Chromatographic Peak Detection Methods for Preprocessing Mass
      Spectrometry Metabolomics Data.
AB  - XCMS and MZmine 2 are two widely used software packages for preprocessing
      untargeted LC/MS metabolomics data. Both construct extracted ion chromatograms
      (EICs) and detect peaks from the EICs, the first two steps in the data
      preprocessing workflow. While both packages have performed admirably in peak
      picking, they also detect a problematic number of false positive EIC peaks and
      can also fail to detect real EIC peaks. The former and latter translate
      downstream into spurious and missing compounds and present significant
      limitations with most existing software packages that preprocess untargeted mass
      spectrometry metabolomics data. We seek to understand the specific reasons why
      XCMS and MZmine 2 find the false positive EIC peaks that they do and in what ways
      they fail to detect real compounds. We investigate differences of EIC
      construction methods in XCMS and MZmine 2 and find several problems in the XCMS
      centWave peak detection algorithm which we show are partly responsible for the
      false positive and false negative compound identifications. In addition, we find
      a problem with MZmine 2's use of centWave. We hope that a detailed understanding
      of the XCMS and MZmine 2 algorithms will allow users to work with them more
      effectively and will also help with future algorithmic development.

PMID- 28752758
TI  - Engineering of Yersinia Phytases to Improve Pepsin and Trypsin Resistance and
      Thermostability and Application Potential in the Food and Feed Industry.
AB  - Susceptibility to proteases usually limits the application of phytase. We sought
      to improve the pepsin and trypsin resistance of YeAPPA from Yersinia
      enterocolitica and YkAPPA from Y. kristensenii by optimizing amino acid polarity
      and charge. The predicted pepsin/trypsin cleavage sites F89/K226 in
      pepsin/trypsin-sensitive YeAPPA and the corresponding sites (F89/E226) in pepsin
      sensitive but trypsin-resistant YkAPPA were substituted with S and H,
      respectively. Six variants were produced in Pichia pastoris for catalytic and
      biochemical characterization. F89S, E226H, and F89S/E226H elevated pepsin
      resistance and thermostability and K226H and F89S/K226H improved pepsin and
      trypsin resistance and stability at 60  degrees C and low pH. All the variants
      increased the ability of the proteins to hydrolyze phytate in corn meal by 2.6
      14.9-fold in the presence of pepsin at 37  degrees C and low pH. This study
      developed a genetic manipulation strategy specific for pepsin/trypsin-sensitive
      phytases that can improve enzyme tolerance against proteases and heat and benefit
      the food and feed industry in a cost-effective way.

PMID- 28752759
TI  - Deconstructing the Catalytic, Vicinal Difluorination of Alkenes: HF-Free
      Synthesis and Structural Study of p-TolIF2.
AB  - Recently, contemporaneous strategies to achieve the vicinal difluorination of
      alkenes via an I(I)/I(III) catalysis manifold were independently reported by this
      laboratory and by Jacobsen and co-workers. Both strategies proceed through a
      transient ArI(III)F2 species generated by oxidation of the ArI catalyst. Herein,
      an efficient synthesis of p-TolIF2 from p-TolI and Selectfluor is presented,
      together with a crystallographic and spectroscopic study. To mitigate safety
      concerns and simplify reaction execution, an HF-free protocol was devised
      employing CsF as a substitute fluoride source. The study provides insight into
      the initial I(I)->I(III) oxidation stage of the catalytic protocol using
      Selectfluor.

PMID- 28752760
TI  - Binary Nanoparticle Graphene Hybrid Structure-Based Highly Sensitive Biosensing
      Platform for Norovirus-Like Particle Detection.
AB  - Nanoparticle (NP)-decorated carbon nanotubes or graphenes (GRPs) have attracted
      attention because of their synergic properties such as enhanced electrical
      conductivity, magneto-optical effect, and plasmon resonance energy transfer.
      These hybrid carbon nanomaterials are widely used in sensing platforms to monitor
      target biomolecules, gases, and chemicals. In this study, binary nanoparticles,
      specifically gold (Au)/magnetic nanoparticle (MNP)-decorated graphenes (GRPs),
      were applied in a virus-sensing platform. This hybrid material exhibited multiple
      functionalities, including magnetic, plasmonic, and enhanced electrical
      properties. The Au/MNP-GRPs were synthesized in two steps at room temperature
      under mild conditions and magnetically deposited on a Pt-interdigitated electrode
      as electrical-sensing channels. After deposition onto the electrode, the surface
      of Au/MNP-GRPs was conjugated with norovirus antibody to produce a norovirus-like
      particle (NoV-LP)-sensing platform. NoV-LPs were successfully detected by the
      hybrid nanomaterial-sensing platform, exhibiting high sensitivity and specificity
      in a concentration range from 0.01 pg to 1 ng. In this case, the limit of
      detection was calculated as 1.16 pg/mL. Thus, the binary nanoparticle-decorated
      graphene shows excellent potential as an electrical-sensing platform for
      biomolecules.

PMID- 28752761
TI  - Water-Soluble Conjugated Polymer as a Fluorescent Probe for Monitoring Adenosine
      Triphosphate Level Fluctuation in Cell Membranes during Cell Apoptosis and in
      Vivo.
AB  - Adenosine triphosphate (ATP) is used as the energy source in cells and plays
      crucial roles in various cellular events. The cellular membrane is the protective
      barrier for the cytoplasm of living cells and involved in many essential
      biological processes. Many fluorescent probes for ATP have been successfully
      developed, but few of these probes were appropriate for visualizing ATP level
      fluctuation in cell membranes during the apoptotic cell death process. Herein, we
      report the synthesis of a new water-soluble cationic polythiophene derivative
      that can be utilized as a fluorescent sensor for detecting ATP in cell membranes.
      Poly((3-((4-methylthiophen-3-yl)oxy)propyl)triphenylphosphonium chloride) (PMTPP)
      exhibits high sensitivity and good selectivity to ATP, and the detection limit is
      27 nM. The polymer shows low toxicity to live cells and excellent photostability
      in cell membranes. PMTPP was practically utilized for real-time monitoring of ATP
      levels in the cell membrane through fluorescence microscopy. We have demonstrated
      that the ATP levels in cell membranes increased during the apoptotic cell death
      process. The probe was also capable of imaging ATP levels in living mice.

PMID- 28752762
TI  - Copper-Catalyzed Oxidative Cyclization of Alkynes with Sulfonylhydrazides Leading
      to 2-Sulfonated 9H-pyrrolo[1,2-a]indol-9-ones.
AB  - A copper-catalyzed oxidative cyclization procedure has been developed for the
      production of 2-sulfonated 9H-pyrrolo[1,2-a]indol-9-ones via the direct
      sulfonylation of N-propargyl-substituted indoles with sulfonylhydrazides and tert
      butyl hydroperoxide (TBHP). This novel protocol, which tolerates a broad range of
      functional groups, offers a simple, efficient, and atom-economical route to a
      series of fluorazones in good yields under mild conditions.

PMID- 28752763
TI  - Polyhydroxylated Quinolizidine Iminosugars as Nanomolar Selective Inhibitors of
      alpha-Glucosidases.
AB  - Polyhydroxylated quinolizidines bearing a hydroxymethyl group at the ring
      junction were synthesized from a readily available l-sorbose-derived ketonitrone.
      Evaluated as glycoside hydrolase inhibitors, these quinolizidines revealed to be
      potent and selective alpha-glucosidase inhibitors. Quinolizidine 9a is the first
      quinolizidine-scaffolded iminosugar exhibiting nanomolar inhibition of a
      glycoenzyme.

PMID- 28752764
TI  - Basin-Scale Observations of Monoterpenes in the Arctic and Atlantic Oceans.
AB  - We report novel in situ speciated observations of monoterpenes (alpha- and beta
      pinene, myrcene, delta3-carene, ocimene, limonene) in seawater and air during
      three cruises in the Arctic and Atlantic Oceans, in/over generally oligotrophic
      waters. Oceanic concentrations of the individual monoterpenes ranged from below
      the detection limit of <1 pmol L-1 to 5 pmol L-1, with average concentrations of
      between 0.5 and 2.9 pmol L-1. After careful filtering for contamination,
      atmospheric mixing ratios varied from below the detection limit (<1 pptv) to 5
      pptv, with averages of 0.05-5 pptv; these levels are up to 2 orders of magnitude
      lower than those reported previously. This could be at least partly due to
      sampling over waters with much lower biological activity than in previous
      studies. Unlike in previous studies, no clear relationships of the monoterpenes
      with biological variables were found. Based on our measured seawater
      concentrations and a global model simulation, we estimate total global marine
      monoterpene emissions of 0.16 Tg C yr-1, similar to a previous bottom-up estimate
      based on laboratory monoculture studies but 2 orders of magnitude lower than a
      previous top-down estimate of 29.5 Tg C yr-1.

PMID- 28752765
TI  - Gold-Embedded Hollow Silica Nanogolf Balls for Imaging and Photothermal Therapy.
AB  - Hybrid nanocarriers with multifunctional properties have wide therapeutic and
      diagnostic applications. We have constructed hollow silica nanogolf balls (HGBs)
      and gold-embedded hollow silica nanogolf balls (Au@SiO2 HGBs) using the layer-by
      layer approach on a symmetric polystyrene (PS) Janus template; the template
      consists of smaller PS spheres attached to an oppositely charged large PS core.
      zeta Potential measurement supports the electric force-based template-assisted
      synthesis mechanism. Electron microscopy, UV-vis, and near-infrared (NIR)
      spectroscopy show that HGBs or Au@SiO2 HGBs are composed of a porous silica shell
      with an optional dense layer of gold nanoparticles embedded in the silica shell.
      To visualize their cellular uptake and imaging potential, Au@SiO2 HGBs were
      loaded with quantum dots (QDs). Confocal fluorescent microscopy and atomic force
      microscopy imaging show reliable endocytosis of QD-loaded Au@SiO2 HGBs in
      adherent HeLa cells and circulating red blood cells (RBCs). Surface-enhanced
      Raman spectroscopy of Au@SiO2 HGBs in RBC cells show enhanced intensity of the
      Raman signal specific to the RBCs' membrane specific spectral markers. Au@SiO2
      HGBs show localized surface plasmon resonance and heat-induced HeLa cell death in
      the NIR range. These hybrid golf ball nanocarriers would have broad applications
      in personalized nanomedicine ranging from in vivo imaging to photothermal
      therapy.

PMID- 28752766
TI  - Photoclinic.

PMID- 28752767
TI  - Differential expression of fatty acid transporters and fatty acid synthesis
      related genes in crop tissues of male and female pigeons (Columba livia
      domestica) during incubation and chick rearing.
AB  - 1. The growth performance of squabs reared solely by male or female parent
      pigeons was measured, and the changes of lipid content of crop milk and the
      expression profiles of genes potentially involved in lipid accumulation by crop
      tissues of parent pigeons were evaluated during incubation and chick rearing. 2.
      Squabs increased in body weight during 25 d of rearing, whereas both male and
      female pigeons lost weight after finishing rearing chicks, and the weight loss of
      male pigeons was significantly greater than that of female parent pigeons. Lipid
      content of crop milk from both parent pigeons gradually decreased to the crude
      fat level in the formulated diet after 10 d (R10) of chick rearing. 3. The gene
      expression of fatty acid translocase (FAT/CD36), fatty acid-binding protein 5
      (EFABP) and acyl-CoA-binding protein (ACBP) in male pigeon crop tissue were the
      greatest at 17 d (I17) of incubation. In female pigeons, FAT/CD36 expression was
      the highest at I14, and both EFABP and ACBP expression peaked at I14 and R7. The
      expression of acetyl-CoA carboxylase and fatty acid synthase in male pigeons
      reached the maximum level at R1, while they peaked at I14 and I17, respectively
      in female pigeons. The gene expression of peroxisome proliferators-activated
      receptor-gamma (PPARgamma) was the greatest at I17 in the male, while it was at
      I14 in the female. However, no regular changing pattern was found in PPARalpha
      gene expression in male pigeons. 4. These results indicated that male and female
      pigeons may make different contributions in rearing squabs. The gene expression
      study suggested that fatty acids used in lipid biosynthesis of crop milk probably
      originated from both exogenous supply and de novo synthesis. The sex of the
      parent pigeon affected the lipid content of crop milk and the expression profiles
      of genes involved in fatty acid transportation and lipogenesis.

PMID- 28752768
TI  - Effects of antiviral therapy in patients with chronic hepatitis B and cirrhosis.
AB  - INTRODUCTION: Hepatitis B virus (HBV) infection is the major cause of cirrhosis
      worldwide. The ultimate goal of current antiviral treatments for chronic
      hepatitis B (nucleos(t)ide analogs and interferon-alpha) is to prevent the
      development of end-stage liver diseases. Areas covered: We present a review of
      the current literature on antiviral therapy in patients with chronic hepatitis B
      and cirrhosis. Medline search was performed to identify relevant literature from
      1993 through January of 2017. Expert commentary: One randomized controlled trial
      and a number of observational studies have shown that nucleos(t)ide analogs can
      decrease the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B
      patients with advanced fibrosis. Data from clinical trials of entecavir and
      tenofovir have shown that histological improvement and regression of fibrosis can
      be achieved in the majority of patients with chronic hepatitis B by successful
      viral suppression. Entecavir and tenofovir are the preferred antiviral agents for
      treatment of chronic hepatitis B in patients with cirrhosis due to their high
      antiviral potency and high genetic barrier to resistance. Pegylated interferon
      alpha is another therapeutic option for chronic hepatitis B patients with well
      compensated cirrhosis. However, interferon therapy is contraindicated in patients
      with decompensated cirrhosis, and evidence for reduced HCC is currently
      insufficient.

PMID- 28752769
TI  - Mutation Spectrum and Genotype-Phenotype Analyses in a Pakistani Cohort With
      Hemophilia B.
AB  - This study aimed to (1) identify F9 genetic alterations in patients with
      hemophilia B (HB) of Pakistani origin and (2) determine the genotype-phenotype
      relationships in these patients. Diagnosed cases of HB were identified through
      registries at designated tertiary health-care centers across the country.
      Consenting patients were enrolled into the study. The factor IX (FIX) coagulation
      activity (FIX:C) and key clinical features were recorded. Direct sequencing of F9
      was carried out in all patients. All the variants identified were analyzed for
      functional consequences employing in silico analysis tools. Accession numbers
      from National Center of Biotechnology Information ClinVar database were retrieved
      for the novel variants. Genotype-FIX:C relationships were determined followed by
      FIX:C clinical phenotype assessment. A total of 52 patients with HB from 36
      unrelated families were identified, which mainly comprised patients with moderate
      HB (n = 35; 67.3%). Among these, 35 patients from 22 unrelated families could be
      contacted and enrolled into the study. Missense variants were the most frequent
      (58.8%), followed by nonsense variants (17.6%). A missense, a short insertion,
      and a nonsense novel variants in exon 2, 6, and 7, respectively, were also
      identified. The disease manifested FIX:C heterogeneity in relation to the
      corresponding mutation in a significant number of cases. Clinical phenotype
      heterogeneity was also observed in relation to FIX:C-based severity assessment.
      We concluded that the registered FIX-deficient population of Pakistan mainly
      comprises moderate HB. F9 mutation spectrum in Pakistani patients with HB is
      heterogeneous. The HB population of Pakistan manifests a significant amount of
      genotype-FIX:C and FIX:C-clinical phenotype heterogeneities.

PMID- 28752770
TI  - Disorders of sex development: Mothers' experiences of support.
AB  - BACKGROUND: An increasing body of research has sought to determine the impact of
      Disorders of Sex Development (DSD) on the family of the affected child. Little is
      currently understood about the support needs of the family and how well these
      needs are met. METHODS: Interpretive Phenomenological Analysis was used to
      analyse semi-structured interviews with eight mothers of children with DSD about
      their experiences of support. RESULTS: Four master themes emerged which
      encapsulated (a) the stages in their child's development when mothers most needed
      support, (b) the importance of developing an understanding of the child's
      condition, (c) the lack of acknowledgement of the emotional needs of the parent
      and (d) the importance of having close and trusted networks for support.
      Continuity and availability of support were considered important and while all
      participants prioritised maintaining privacy about the condition, a minority felt
      that this impacted the level of support they received. CONCLUSIONS: Key time
      points for support were identified and while some felt that they were well
      supported others felt that the support available did not meet their emotional
      needs. Clinical implications and directions for future research were considered.

PMID- 28752771
TI  - Psychomotor, functional, and cognitive profiles in older people with and without
      dementia: What connections?
AB  - Background In typical aging, it is possible to observe a decline in psychomotor
      domains, such as balance or global and fine motor skills as well as a cognitive
      and functional decline. Although, it is not clear which psychomotor domains are
      mostly affected in elderly with dementia and the association with the cognitive
      and functional level. Objective To identify the correlation between psychomotor,
      cognitive, and functional skills, and seeking whether there are differences among
      persons with and without dementia. Design and Methods A total of 120 persons with
      dementia (ages between 61 and 99 years old; mean age 80.6 +/- 7.4) and 377
      persons without dementia (ages between 60 and 99 years old; mean age 77.2 +/-
      8.7) were recruited from nursing homes, day-care centers, and home care.
      Consenting participants were assessed in psychomotor, cognitive, and functional
      domains using the Mini Mental State Examination (MMSE) to assess cognitive
      impairment, the Barthel Index (BI), and Lawton Index (LI) to identify basic and
      instrumental activities of daily living and a Portuguese Version of Examen
      Geronto-Psychomoteur (P-EGP) to evaluate psychomotor skills. Results People with
      dementia showed a higher percentage of cognitive deficit and higher level of
      dependency in basic and instrumental activities of daily living. Further,
      findings also showed significant differences in psychomotor domains and total of
      P-EGP, with exception of Joint Mobilizations of Upper and Lower Limbs. There were
      moderate to strong correlations between the totals of the scales, and between the
      totals and domains. Conclusions The population with dementia has higher
      percentage of cognitive deficit, higher dependency on the performance of basic
      and instrumental activities of daily living and poorer psychomotor performance,
      except in joint mobilizations. It was also possible to find strong correlations
      between the total of P-EGP and the total of cognitive and functional scales.
      Implications for future research and practice are discussed.

PMID- 28752772
TI  - Being a 'good' parent: single women reflecting upon 'selfishness' and 'risk' when
      pursuing motherhood through sperm donation.
AB  - Drawing upon the narratives of 23 single heterosexual women in the UK thinking
      about and pursuing motherhood through sperm donation, this paper explores how
      solo motherhood can be construed as a 'risk' to the identity of a 'good' mother.
      It shows how, for these women, solo motherhood was a departure from an imagined
      life of having a child within the context of a stable relationship and was a
      prospect viewed with much ambivalence and uncertainty. Choosing to become a
      single mother challenged their conceptualisation of a 'good' mother, someone who
      puts their child's interests above their own. By examining the flexible and
      creative ways these women navigate the field of reproductive technologies in the
      pursuit of motherhood, this paper explores how the women engaged in a process of
      'damage limitation', becoming 'moral pioneers' of family and relatedness, as they
      realigned their ideals versus realities of family building and tried to make solo
      motherhood as 'good as it can be' for their future child.

PMID- 28752773
TI  - Estimating the barcoding gap in a global dataset of cox1 sequences for Odonata:
      close, but no cigar.
AB  - We evaluated the extent of intraspecific and interspecific genetic distances for
      two highly diverse infraorders of Odonata: Anisoptera and Zygoptera. All
      cytochrome c oxidase subunit I sequences (cox1), the region chosen for zoological
      DNA barcoding, present in GenBank for each infraorder were downloaded and
      curated. For Anisoptera, the final dataset consisted of 2,961 individual cox1
      sequences for 536 species and the equivalent numbers for Zygoptera were 2,477
      sequences for 497 species. More than 7 million individual genetic comparisons
      were made and the results indicated that there is a tendency towards a barcoding
      gap, but that the size of the gap may not be sufficient to robustly infer
      identities for some taxa. DNA barcoding may be of less use for some odonate taxa,
      perhaps pertaining to misidentifications in global databases. However, at local
      scales or with more confined taxonomical sampling, this tool may yet be
      beneficial in identifying these charismatic organisms.

PMID- 28752774
TI  - Erratum.

PMID- 28752775
TI  - Significant genetic differentiation of Gobiopterus lacustris, a newly recorded
      transparent goby in China.
AB  - In our recent survey, the transparent small Lacustrine goby, Gobiopterus
      lacustris had reported as the endemic species of Luzon, Philippines, was
      identified as an abundant species in mangroves of Leizhou Peninsula, China. Here,
      high diversity and significant differentiation of five sites of samples
      representing the west and east populations were revealed by mitochondrial DNA
      sequences. Five haplotypes of 56 cytochrome oxidase subunit I (Cox1) with the
      lengths of 623 base pairs (bp) have the high pairwise identity (>98.8%).
      Moreover, a total of 31 haplotypes for 129 partial D-loop regions were clustered
      into two clades corresponding to the east and west sampling sites. The strong
      population structure was confirmed (PhiST = 0.43017, p < .0001) with high
      haplotype diversity (h = 0.880 +/- 0.017) and low nucleotide diversity
      (p=.00484). Moreover, both the mismatch distribution analysis and neutral test of
      D-loop revealed that the west group might experience a recent demographic
      expansion. Lastly, the isolation-with-migration analysis supported the expansion
      and indicated that the east-west split happened at approximately 7.1 kyr ago.
      Given the distribution and diversity, G. lacustris could be a good model for the
      study of the sea-level fluctuations and coast evolution of the South China Sea.

PMID- 28752776
TI  - Efficacy and safety of inhaled corticosteroids relative to fluticasone
      propionate: a systematic review of randomized controlled trials in asthma.
AB  - INTRODUCTION: Many trials have been published comparing inhaled corticosteroid
      (ICS) treatments in asthma. However, mixed results necessitate the summarization
      of available evidence to aid in decision-making. Areas covered: This systematic
      review evaluated randomized controlled trials (RCTs) that compared the efficacy
      and safety of inhaled fluticasone propionate (FP) with other ICS including
      beclomethasone dipropionate (BDP), budesonide (BUD) and ciclesonide (CIC). PubMed
      was searched and 54 RCTs that fit pre-determined criteria were included.
      Endpoints evaluated included lung function, asthma symptom control, exacerbation
      frequency, reliever use, quality of life and steroid-related side effects. Expert
      commentary: Across all studies, FP was associated with either more favorable or
      at least similar efficacy and safety, in comparison with BDP or BUD. This
      observation may be related to FP's higher relative potency and almost negligible
      oral bioavailability. FP was comparable to CIC for efficacy. However, CIC
      appeared to have a smaller impact on cortisol levels than FP, which is likely due
      to CIC's incomplete conversion to active metabolite (des-CIC) and the lower
      potency of des-CIC compared with FP. Although there were no significant
      differences in evaluated outcomes after treatment with different ICS in the
      majority of studies, some observed differences could be explained by their
      respective pharmacodynamic and pharmacokinetic properties.

PMID- 28752777
TI  - Anti-EGFR monoclonal antibody panitumumab for the treatment of patients with
      metastatic colorectal cancer: an overview of current practice and future
      perspectives.
AB  - INTRODUCTION: Targeted agents alone or in combination with chemotherapy are
      current standard of treatment for metastatic colorectal cancer (mCRC).
      Panitumumab is a fully human monoclonal antibody which inhibits the epidermal
      growth factor receptor (EGFR). It is currently approved in combination with
      chemotherapy in first- and second-line and as a monotherapy in chemorefractory
      patients. RAS gene mutations confer resistance to anti-EGFR agents; thus,
      panitumumab is restricted to the treatment of RAS wild-type (WT) tumors. Areas
      covered: This review explores the available data on panitumumab and presents new
      perspectives on predictive markers of anti-EGFR efficacy including primary tumor
      sidedness and BRAF mutations. Other details covered include panitumumab's
      mechanism of action, pharmacokinetics, pharmacodynamics and safety aspects of the
      therapy as well as mechanisms of secondary resistance and future prospects of
      treatment in different settings. Expert opinion: Panitumumab has significantly
      added to the treatment armamentarium for RAS WT mCRC. The effort spent in
      identifying predictive biomarkers of panitumumab efficacy has been of pivotal
      importance to development of the molecular selection of patients with mCRC.
      Primary and secondary resistance, however, still represent important issues.
      Novel strategies to overcome those issues are currently underway with promising
      results which highlight the potential use of panitumumab in combination with
      other targeted agents in the future.

PMID- 28752778
TI  - Doctors-managers: Is still worthy?

PMID- 28752779
TI  - Reply to letter "Is Pruritus an indicator of Aquaporin-positive Neuromyelitis
      Optica?"

PMID- 28752780
TI  - Letter re "Is pruritus an indicator of aquaporin-positive neuromyelitis optica?"

PMID- 28752782
TI  - The feasibility of substituting left atrial wall strain for flow velocity of left
      atrial appendage.
AB  - OBJECTIVE: Non-valvular atrial fibrillation (NVAF) is frequently complicated by
      thromboembolism. Left atrial appendage (LAA) flow is a predictor of LAA
      thrombosis. LAA flow is measured by transesophageal echocardiography (TEE), which
      is a semi-invasive diagnostic tool. Recently, speckle-tracking methods have been
      adapted for the evaluation of local cardiac function. We hypothesised that if we
      could determine LAA wall motion utilising a speckle tracking technique, we could
      non-invasively analyse LAA flow. METHODS: Sixty-three NVAF patients including 38
      with chronic atrial fibrillation (CAF), 14 with paroxysmal AF (PAF) and 11 with
      atrial flutter (AFL) were enrolled in this study. Normal sinus rhythm (NSR)
      patients with non-thromboembolic cerebral infarction were also included.
      Immediately after obtaining a 2D movie of the LAA through the aortic oblique
      short axis view by transthoracic echocardiography, LAA flow velocity was measured
      by TEE. Mean strains between the posterior and anterior walls were measured using
      a speckle-tracking technique. RESULTS: Ten patients exhibited a thrombus and 11
      had spontaneous echo contrast (SEC) in the auricle. Mean strain value was similar
      between CAF and PAF, although LAA flow velocity for CAF was significantly reduced
      compared with PAF (median value 13.7 cm/s versus 36.1 cm/s, p = <.00001). Mean
      strain of CAF with thrombus/SEC was significantly reduced compared with NSR
      patients (median value 1.52% versus 3.17%, p = .00181). Furthermore, mean strain
      was correlated with LAA flow velocity (R = 0.399, R2 = 0.1595, p = .000615).
      CONCLUSIONS: LAA wall strain identified via speckle-tracking methods may presage
      LAA peak flow velocity. This technique may contribute to stratification of
      thrombosis risks in the LAA.

PMID- 28752781
TI  - Is age a key factor contributing to the disparity between success of
      neuroprotective strategies in young animals and limited success in elderly stroke
      patients? Focus on protein homeostasis.
AB  - Neuroprotection strategies to improve stroke outcome have been successful in the
      laboratory but not in clinical stroke trials, and thus have come under scrutiny
      by the medical community. Experimental stroke investigators are therefore under
      increased pressure to resolve this problem. Acute ischemic stroke represents a
      severe form of metabolic stress that activates many pathological processes and
      thereby impairs cellular functions. Traditionally, neuroprotection strategies
      were designed to improve stroke outcome by interfering with pathological
      processes triggered by ischemia. However, stroke outcome is also dependent on the
      brain's capacity to restore cellular functions impaired by ischemia, and this
      capacity declines with age. It is, therefore, conceivable that this age-dependent
      decline in the brain's self-healing capacity contributes to the disparity between
      the success of neuroprotective strategies in young animals, and limited success
      in elderly stroke patients. Here, prosurvival pathways that restore protein
      homeostasis impaired by ischemic stress should be considered, because their
      capacity decreases with increasing age, and maintenance of proteome fidelity is
      pivotal for cell survival. Boosting such prosurvival pathways pharmacologically
      to restore protein homeostasis and, thereby, cellular functions impaired by
      ischemic stress is expected to counterbalance the compromised self-healing
      capacity of aged brains and thereby help to improve stroke outcome.

PMID- 28752783
TI  - Reactive oxygen species-based measurement of the dependence of the Coulomb
      nanoradiator effect on proton energy and atomic Z value.
AB  - PURPOSE: The Coulomb nanoradiator (CNR) effect produces the dose enhancement
      effects from high-Z nanoparticles under irradiation with a high-energy ion beam.
      To gain insight into the radiation dose and biological significance of the CNR
      effect, the enhancement of reactive oxygen species (ROS) production from iron
      oxide or gold NPs (IONs or AuNPs, respectively) in water was investigated using
      traversing proton beams. METHODS AND MATERIALS: The dependence of nanoradiator
      enhanced ROS production on the atomic Z value and proton energy was investigated.
      Two biologically important ROS species were measured using fluorescent probes
      specific to *OH or [Formula: see text] in a series of water phantoms containing
      either AuNPs or IONs under irradiation with a 45- or 100-MeV proton beam.
      RESULTS: The enhanced generation of hydroxyl radicals (*OH) and superoxide anions
      ([Formula: see text]) was determined to be caused by the dependence on the NP
      concentration and proton energy. The proton-induced Au or iron oxide
      nanoradiators exhibited different ROS enhancement rates depending on the proton
      energy, suggesting that the CNR radiation varied. The curve of the superoxide
      anion production from the Au-nanoradiator showed strong non-linearity, unlike the
      linear behavior observed for hydroxyl radical production and the X-ray
      photoelectric nanoradiator. In addition, the 45-MeV proton-induced Au
      nanoradiator exhibited an ROS enhancement ratio of 8.54/1.50 ([Formula: see text]
      / *OH), similar to that of the 100-KeV X-ray photoelectric Au nanoradiator
      (7.68/1.46). CONCLUSIONS: The ROS-based detection of the CNR effect revealed its
      dependence on the proton beam energy, dose and atomic Z value and provided
      insight into the low-linear energy transfer (LET) CNR radiation, suggesting that
      these factors may influence the therapeutic efficacy via chemical reactivities,
      transport behaviors, and intracellular oxidative stress.

PMID- 28752784
TI  - Commentary on "Localized pigmentation disorder after subcutaneous pegylated
      interferon beta 1a injection" by Coghe et al.

PMID- 28752785
TI  - Localized pigmentation disorder after subcutaneous pegylated interferon beta-1a
      injection.
AB  - We report the case of a 42-year-old female patient who developed peculiar skin
      lesions due to subcutaneous polyethylene glycol (PEG) interferon beta-1a. The
      dermatological examination showed hypochromic macules that had coalesced into a
      10-cm-diameter patch. On the abdomen injection sites, there was a greyish diffuse
      hyperpigmentation arranged irregularly in annular macules. Fungal infection,
      vitiligo and pityriasis alba were excluded. After 6 months, the lesions had
      worsened. This is the first case of localized pigmentation disorder reported with
      interferon beta, and while the clinical findings are not ascribable to vitiligo
      or interferon-related facial/mucosal hyperpigmentation, they may partially share
      the underlining mechanisms.

PMID- 28752786
TI  - Serum microRNA-302b: the novel biomarker for diagnosis of acute myocardial
      infarction.

PMID- 28752787
TI  - The Xenopus tadpole: An in vivo model to screen drugs favoring remyelination.
AB  - BACKGROUND: In multiple sclerosis, development of screening tools for
      remyelination-promoting molecules is timely. OBJECTIVE: A Xenopus transgenic line
      allowing conditional ablation of myelinating oligodendrocytes has been adapted
      for in vivo screening of remyelination-favoring molecules. METHODS: In this
      transgenic, the green fluorescent protein reporter is fused to E. coli
      nitroreductase and expressed specifically in myelinating oligodendrocytes.
      Nitroreductase converts the innocuous pro-drug metronidazole to a cytotoxin.
      Spontaneous remyelination occurs after metronidazole-induced demyelinating
      responses. As tadpoles are transparent, these events can be monitored in vivo and
      quantified. At the end of metronidazole-induced demyelination, tadpoles were
      screened in water containing the compounds tested. After 72 h, remyelination was
      assayed by counting numbers of oligodendrocytes per optic nerve. RESULTS: Among a
      battery of molecules tested, siponimod, a dual agonist of sphingosine-1-phosphate
      receptor 1 and 5, was among the most efficient favoring remyelination.
      Crispr/cas9 gene editing showed that the promyelinating effect of siponimod
      involves the sphingosine-1-phosphate receptor 5. CONCLUSION: This Xenopus
      transgenic line constitutes a simple in vivo screening platform for myelin repair
      therapeutics. We validated several known promyelinating compounds and
      demonstrated that the strong remyelinating efficacy of siponimod implicates the
      sphingosine-1-phosphate receptor 5.

PMID- 28752788
TI  - Occupational Social Class and Personality Traits in Relation to Leisure-Time
      Physical Activity Level: Cross-Sectional Results From the Copenhagen Aging and
      Midlife Biobank.
AB  - OBJECTIVE: To investigate separate and combined associations of occupational
      social class and personality traits with late midlife leisure-time physical
      activity duration and intensity. METHOD: Cross-sectional data from the Copenhagen
      Aging and Midlife Biobank ( N = 4,649) were analyzed using linear regression
      models with leisure-time physical activity (metric equivalence) as outcome.
      RESULTS: Low versus high occupational social class was associated with 4% (95%
      confidence interval [CI] = [3%, 5%]) greater leisure-time physical activity
      duration, but 2% (CI = [1%, 3%]) lower intensity. Each 10-unit increase in
      extraversion was associated with 5% (CI = [2%, 8%]) greater duration. Intensity
      increased by each 10-unit increase in conscientiousness (6%, CI = [4%, 7%]),
      openness (3%, CI = [1%, 4%]), neuroticism (3%, CI = [1%, 4%]), and extraversion
      (5%, CI = [4%, 7%]). Conscientiousness was positively associated with duration in
      low, but not in high, occupational social class (interaction p value = .002).
      DISCUSSION: Higher occupational social class was associated with lower leisure
      time physical activity duration, but higher intensity. Extraversion was
      positively associated with duration and intensity. Conscientiousness, openness,
      and neuroticism were positively associated with intensity. Overall, interactions
      were not consistent.

PMID- 28752789
TI  - Discrepancy analysis and Australian norms for the Trail Making Test.
AB  - OBJECTIVE: Discrepancy analyses refer to comparison methods that evaluate the
      relationship or differences between two measures in the same individual. A common
      type of discrepancy analysis involves the comparison of two trials within a
      measure, such as, Trails A and B of the Trail Making Test (TMT). The TMT is well
      suited to this role as the two measures are highly correlated, assess similar
      underlying constructs, and most importantly demonstrate differential
      vulnerability to the impact of pathology. While the inclusion of these types of
      data in the form of difference scores or ratios has become more frequent, this
      information has been presented only for demographically adjusted subgroups and
      has not taken into account the level of performance of the comparison trial,
      Trails A. METHOD: The role and advantages of discrepancy analysis with the TMT
      stratified by level of Trails A performance were demonstrated with an Australian
      normative sample of 647 participants and a heterogeneous clinical sample
      consisting of 2,292 Australian and U.S. CASES:  RESULTS: The ability to
      differentiate between the influence of slowed visual scanning and/or graphomotor
      speed, and reduced mental flexibility was demonstrated by applying the normative
      data to clinical case discrepancies. The importance of accounting for the
      variability in discrepancy scores associated with the level of performance of
      Trails A was also highlighted. CONCLUSION: A simple, efficient, and effective
      approach to examining the basis for differences between TMT-A and TMT-B
      performances is provided to examine the relative contributions of
      perceptual/motor abilities, and mental flexibility.

PMID- 28752790
TI  - pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion
      than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke.
AB  - Diffusion weighted imaging (DWI) has been commonly used in acute stroke
      examination, yet a portion of DWI lesion may be salvageable. Recently, it has
      been shown that diffusion kurtosis imaging (DKI) defines the most severely
      damaged DWI lesion that does not renormalize following early reperfusion. We
      postulated that the diffusion and kurtosis lesion mismatch experience
      heterogeneous hemodynamic and/or metabolic injury. We investigated tissue
      perfusion, pH, diffusion, kurtosis and relaxation from regions of the
      contralateral normal area, diffusion lesion, kurtosis lesion and their mismatch
      in an animal model of acute stroke. Our study revealed significant kurtosis and
      diffusion lesion volume mismatch (19.7 +/- 10.7%, P < 0.01). Although there was
      no significant difference in perfusion and diffusion between the kurtosis lesion
      and kurtosis/diffusion lesion mismatch, we showed lower pH in the kurtosis lesion
      (pH = 6.64 +/- 0.12) from that of the kurtosis/diffusion lesion mismatch (6.84 +/
      0.11, P < 0.05). Moreover, pH in the kurtosis lesion and kurtosis/diffusion
      mismatch agreed well with literature values for regions of ischemic core and
      penumbra, respectively. Our work documented initial evidence that DKI may reveal
      the heterogeneous metabolic derangement within the commonly used DWI lesion.

PMID- 28752791
TI  - Effect of tibial coronal inclination on hindfoot kinematics: A biomechanical
      simulation study.
AB  - Tibial coronal inclination is often recognized in everyday life, but the
      compensatory kinematic changes to maintain plantigrade of the hindfoot in
      response to tibial coronal inclination remain unclear. Lower legs and foot
      specimens obtained from seven human cadavers were loaded vertically with traction
      of Achilles' tendon in different tibial inclinations: 0 degrees  (neutral), 5
      degrees , and 10 degrees  medial inclination, and 5 degrees  and 10 degrees 
      lateral inclination. The orientations of the tibia, talus, and calcaneus were
      recorded under vertical load by a three-dimensional digitizing stylus. The
      angular changes of the talocrural and subtalar joints in the tibial inclinations
      from neutral were analyzed. The heights of the origins of the talus and calcaneus
      were also recorded. As the tibia was medially inclined from neutral, the
      talocrural joint was significantly more dorsiflexed. The subtalar joint was
      significantly more inverted, plantarflexed, and internally rotated. However, such
      significant changes in the joint angles were not observed when the tibia was
      laterally inclined. The height of the talus decreased as the tibia was medially
      inclined, but it was vice versa when laterally inclined. The compensatory motions
      of the hindfoot to tibial medial inclination involved coupled movement of both
      the talocrural and subtalar joints; such motions flatten the medial foot by
      decreasing the height of the talus. However, such compensatory capacities of the
      hindfoot to tibial lateral inclinations were limited. Tibial medial inclination
      under axial loading affects the kinematics of the hindfoot, and this is an
      important factor to consider in the treatment of flatfoot as well as foot
      orthotic/footwear intervention.

PMID- 28752792
TI  - Strain distribution in the porcine lumbar laminae under asymmetric loading.
AB  - If the articular facets of the vertebra grow in an asymmetric manner, the
      developed geometry causes an asymmetry of loading. When the loading environment
      is altered by way of increased activity, the likelihood of acquiring a stress
      fracture may be increased. The combination of geometric asymmetry and increased
      activity is hypothesised to be the precursor to the stress fracture under
      investigation in this study, spondylolysis. This vertebral defect is an acquired
      fracture with 7% prevalence in the paediatric population. This value increases to
      21% among athletes who participate in hyperextension sports. Tests were carried
      out on porcine lumbar vertebrae, on which the effect of facet angle asymmetry was
      simulated by offsetting the load laterally by 7 mm from the mid-point. The aim of
      the study is to investigate whether an increase in the coronal orientation of one
      facet leads to an increase in strain in the corresponding vertebral lamina.
      Strain in the laminae was recorded using six 3-element stacked rosette strain
      gauges placed bilaterally. Results show that a significant linear predictive
      relationship exists between load offset and average strain level in the vertebral
      laminae with p values of 0.006 and 0.045 for principal strains epsilon1 and
      epsilon2 on the right-hand side, and p-values of 0.009 and 0.001 for principal
      strains epsilon1 and epsilon2 on the left-hand side ( R2 all >0.9). This study
      concludes that facet angle asymmetry does lead to a difference in strain in the
      vertebral laminae. Change in principal strain as a result of facet asymmetry has
      a linear relationship and an asymmetry threshold exists beyond which compressive
      strain on the more coronally oriented facet can be increased by up to 15%.

PMID- 28752793
TI  - A tale of two norms: the impact of normative sample selection criteria on
      standardized scores in older adults.
AB  - OBJECTIVE: Normative sample composition can vary notably as a function of
      exclusionary criteria in older adult samples given that typical medical
      conditions of exclusion become more prevalent with age. Older adult norms may
      consist of typically aging or healthy aging individuals according to the
      stringency of the exclusion criteria, a difference illustrated when comparing two
      normative samples for the RBANS: the original standardization sample and the
      Oklahoma sample. METHODS: The current study examined the clinical impact of norm
      selection in older adults by analyzing impairment classification rates for 105
      older adult behavioral health inpatients. Rates of impaired performance (scaled
      score <=4 or its normalized equivalent) were compared across RBANS subtests using
      standardization sample vs. Oklahoma sample normative data in patients aged 70-79
      (n = 57) and 80-89 (n = 48). RESULTS: Across most RBANS subtests, utilization of
      the original standardization sample vs. Oklahoma sample norms resulted in a
      greater proportion of individuals classified as impaired. These findings occurred
      across both age groups and persevered when holding constant the sample
      normalization process. Overall, use of the standardization sample vs. Oklahoma
      sample normative data were 1-11 times more likely to indicate impairment, with
      one of the more notable differences seen on the Coding subtest in the 80-89
      sample (65% vs. 8% labeled as impaired). CONCLUSIONS: Sample composition and
      exclusionary criteria require consideration when selecting an appropriate
      normative sample against which to compare older adult test performance. Salient
      differences between typically aging vs. healthy aging older adult norms are
      discussed.

PMID- 28752794
TI  - Relationship between perceived organizational justice and moral distress in
      intensive care unit nurses.
AB  - BACKGROUND: The nature of the nursing profession pays more attention to ethics of
      healthcare than its therapeutic dimension. One of the prevalent moral issues in
      this profession is moral distress. Moral distress appears more in intensive care
      units due to the widespread need for moral decision-making regarding treatment
      and care in emergency situations. In this connection, organizational justice is
      of high importance and, as a significant motivational tool, leaves important
      impacts upon attitude and behavior of personnel. AIM/OBJECTIVE: This study aimed
      at investigation of the relationship between perceived organizational justice and
      moral distress in intensive care unit nurses. RESEARCH DESIGN: This is a
      descriptive-correlational research which examined the relationship between
      perceived organizational justice and moral distress in intensive care unit
      nurses. Participants and research context: A total of 284 intensive care unit
      nurses were selected via census sampling. The data were collected through
      questionnaires and then were analyzed via SPSS-20 using Pearson and Spearman
      correlation tests. Ethical considerations: This study was approved by the
      Committee of Ethics in Medical Research. Completion of informed consent form,
      guarantee of the confidentiality of information, explanation on purposes of the
      research, and voluntary participation in the study were moral considerations
      observed in this study. FINDINGS: There was a statistically significant negative
      correlation between the total perceived organizational justice and the total
      moral distress (p = 0.024, r = -0.137) and also between "procedural and
      interactional justice and errors" and "not respecting the ethics principles."
      Meanwhile, no relationship was found by the findings between distributive justice
      and dimensions of moral distress. CONCLUSION: According to the results of the
      study, there was a reverse significant relationship between moral distress and
      perceived organizational justice; therefore, the head nurses are expected to
      contribute to reduce moral distress and to increase perceived organizational
      justice in nurses.

PMID- 28752795
TI  - Bovine milk-derived alpha-lactalbumin prevents hepatic fibrosis induced by
      dimethylnitrosamine via nitric oxide pathway in rats.
AB  - The present study was designed to evaluate the hepatoprotective potential of
      alpha-lactalbumin (alphaLA) against dimethylnitrosamine (DMN)-induced toxic
      insults in the rat liver. The liver damage was induced in rats by the repeated
      administration of DMN (10 mg/kg, i.p.) on three consecutive days per week for
      three weeks. The rats were maintained on either a standard AIN-93 M or alphaLA
      enriched diet starting one week before the DMN injection until the termination of
      the experiment. The DMN treatment produced a progressive increase in the plasma
      markers (aspartate aminotransferase, alanine aminotransferase, total bililbin,
      hyarulonic acid, and matrix metalloproteinase-2) in 28 days after the first DMN
      injection. Dietary treatment with alphaLA significantly reduced the DMN-induced
      damage toward normalcy. NG-nitro-L-arginine methyl ester, a nitric oxide synthase
      inhibitor, significantly attenuated the hepatoprotective effect of alphaLA. These
      findings show that alphaLA has a marked suppressive effect on hepetic fibrosis
      through a nitric oxide-mediated mechanism.

PMID- 28752796
TI  - Lay Listener Classification and Evaluation of Typical and Atypical Children's
      Speech.
AB  - Verbal children with autism spectrum disorder (ASD) often also have atypical
      speech. In the context of the many challenges associated with ASD, do speech
      sound pattern differences really matter? The current study addressed this
      question. Structured spontaneous speech was elicited from 34 children: 17 with
      ASD, whose clinicians reported unusual speech prosody; and 17 typically
      developing, age-matched controls. Multiword utterances were excerpted from each
      child's speech sample and presented to young adult listeners, who had no clinical
      training or experience. In Experiment 1, listeners classified band pass filtered
      and unaltered excerpts as "typical" or "disordered". Children with ASD were only
      distinguished from typical children based on unaltered speech, but the analyses
      indicated unique contributions from speech sound patterns. In Experiment 2,
      listeners provided likeability ratings on the filtered and unaltered excerpts.
      Again, lay listeners only distinguished children with ASD from their typically
      developing peers based on unaltered speech, with typical children rated as more
      likeable than children with ASD. In Experiment 3, listeners evaluated the
      unaltered speech along several perceptual dimensions. High overlap between the
      dimensions of articulation, clearness, and fluency was captured by an emergent
      dimension: intelligibility. This dimension predicted listeners' likeability
      ratings nearly as well as it predicted their judgments of disorder. Overall, the
      results show that lay listeners can distinguish atypical from typical children
      outside the social-interactional context based solely on speech, and that they
      attend to speech intelligibility to do this. Poor intelligibility also
      contributes to listeners' negative social evaluation of children, and so merits
      assessment and remediation.

PMID- 28752797
TI  - The bird dancer and the warrior king: Divergent lived experiences of Tourette
      syndrome in Bali.
AB  - In the past two decades, ethnographic, epidemiological and interdisciplinary
      research has robustly established that culture is significant in determining the
      long-term outcomes of people with neurodevelopmental, neuropsychiatric and mood
      disorders. Yet these cultural factors are certainly not uniform across discrete
      individual experiences. Thus, in addition to illustrating meaningful differences
      for people with neuropsychiatric disorder between different cultures, ethnography
      should also help detail the variations within a culture. Different subjective
      experiences or outcomes are not solely due to biographical idiosyncrasies-rather,
      influential factors arising from the same culture can have different impacts on
      different people. When taking a holistic and intersectional perspective on lived
      experience, it is crucial to understand the interaction of these factors for
      people with neuropsychiatric disorders. This paper teases apart such
      interactions, utilizing comparative case studies of the disparate subjective
      experiences and illness trajectories of two Balinese people with Tourette
      syndrome who exhibit similar symptoms. Based on longitudinal person-centered
      ethnography integrating clinical, psychological, and visual anthropology, this
      intersectional approach goes beyond symptom interpretation and treatment
      modalities to identify gendered embodiment and marital practices as influenced by
      caste to be significant determinants in subjective experience and long-term
      outcome.

PMID- 28752798
TI  - Primary headaches in patients with temporomandibular disorders: Diagnosis and
      treatment of central sensitization pain.
AB  - OBJECTIVES: Central sensitization (CS) has been found in patients with
      temporomandibular disorders (TMD), craniofacial pain (CP) and primary headaches,
      but its clinical implications remain uncertain. The first aim was to provide a
      synthesis of the current state of knowledge about the link between CS and TMD
      associated with primary headaches; the second goal was to find methodologies to
      assess and treat CS in this subgroup of patients. METHODS: A narrative review of
      the literature was conducted. RESULTS: CS is described in literature as an
      aggravating factor in patients with TMD-related primary headaches. Further
      studies are required to support this assertion. CONCLUSIONS: The importance of
      excluding chronic neuropathic pain and recognizing CS as the main component using
      a top-down approach to target the best pharmacological and non-pharmacological
      treatments is evident. Some useful tools to discriminate patients with CS from
      others have become available, but more research is required to enable an
      appropriate diagnosis.

PMID- 28752799
TI  - Residue-based iron oxide catalyst for the degradation of simulated petrochemical
      wastewater via heterogeneous photo-Fenton process.
AB  - Iron oxide with a high degree of purity was recovered from waste and used as an
      environmentally friendly, low-cost catalyst in the application of the photo
      Fenton process to simulated petrochemical wastewater (SPW). Iron oxide
      nanoparticles were characterized by X-ray powder diffraction, transmission
      electron microscopy, N2 adsorption/desorption isotherms, zeta potential, toxicity
      and atomic absorption spectrometry. The experiments were performed in a batch
      photochemical reactor, at 20 +/- 2.0 degrees C and pH 3.0. The SPW was
      efficiently mineralized and oxidized using a low catalyst dosage. The results
      showed that the organic compounds present in the wastewater were not adsorbed
      onto the solid surface. The solid was found to be stable with negligible leaching
      and low toxicity. The kTOC/kCOD ratios were calculated and varied according to
      the process: for a homogeneous reaction, the ratio obtained was 0.31 and for the
      heterogenous photo-Fenton process, it was closer to 1. The chemical oxygen demand
      and total organic carbon removal values were very close, indicating that the SPW
      is immediately mineralized, without producing partially oxidized compounds. The
      residue-based goethite studied represents a good alternative to commercially
      available catalysts in terms of sources and availability.

PMID- 28752800
TI  - Can resistance training impact MRI outcomes in relapsing-remitting multiple
      sclerosis?
AB  - BACKGROUND: Multiple sclerosis (MS) is characterised by accelerated brain
      atrophy, which relates to disease progression. Previous research shows that
      progressive resistance training (PRT) can counteract brain atrophy in other
      populations. OBJECTIVE: To evaluate the effects of PRT by magnetic resonance
      imaging (MRI) and clinical measures of disease progression in people with MS.
      METHODS: This study was a 24-week randomised controlled cross-over trial,
      including a Training ( n = 18, 24 weeks of PRT followed by self-guided physical
      activity) and Waitlist group ( n = 17, 24 weeks of habitual lifestyle followed by
      PRT). Assessments included disability measures and MRI (lesion load, global brain
      volume, percentage brain volume change (PBVC) and cortical thickness). RESULTS:
      While the MS Functional Composite score improved, Expanded Disability Status
      Scale, lesion load and global brain volumes did not differ between groups. PBVC
      tended to differ between groups and higher absolute cortical thickness values
      were observed in 19 of 74 investigated cortical regions after PRT. Observed
      changes were confirmed and reproduced when comparing relative cortical thickness
      changes between groups for four areas: anterior cingulate gyrus, temporal pole,
      orbital sulcus and inferior temporal sulcus. CONCLUSION: PRT seem to induce an
      increase in cortical thickness, indicating that PRT have a neuroprotective or
      even neuroregenerative effect in relapsing-remitting MS.

PMID- 28752801
TI  - Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact
      of some benzimidazole derivatives.
AB  - Virus-directed enzyme prodrug therapy is one of the major strategy of increasing
      cytotoxicity of bioreductive agents. This research intended to examine new
      selected benzimidazole derivatives as a substrate for nitroreductase, the enzyme
      involved in nitroreduction which is responsible to the production of cytotoxic
      metabolites. In this way, the selectivity and strength of cytotoxicity can be
      raised. The effect of benzimidazoles on virus transfected cells and non-virus
      transfected cells A549 cell line was established by Annexin V + propidium iodide
      test, western blot, and polymerase chain reaction analysis of specific pro- and
      anti-apoptotic proteins in the corresponding gene expression and additionally
      nitroreductase gene expression. Our results proved the pro-apoptotic properties
      of all tested compounds in normoxia and hypoxia, especially according to virused
      A549 cells where the time of exposition was reduced from 48 to 4 h. In this
      shorten period of time, the strongest activity was shown by N-oxide compounds
      with nitro-groups. The apoptosis was confirmed by generation of BAX gene and
      protein and reduction of BCL2 gene and protein.

PMID- 28752802
TI  - Three-dimensional wet-electrospun poly(lactic acid)/multi-wall carbon nanotubes
      scaffold induces differentiation of human menstrual blood-derived stem cells into
      germ-like cells.
AB  - Infertility caused by the disruption or absence of germ cells is a major and
      largely incurable medical problem. Germ cells (i.e., sperm or egg) play a key
      role in the transmission of genetic and epigenetic information across
      generations. Generation of gametes derived in vitro from stem cells hold
      promising prospects which could potentially help infertile men and women.
      Menstrual blood-derived stem cells are a unique stem cell source. Evidence
      suggests that menstrual blood-derived stem cells exhibit a multi-lineage
      potential and have attracted extensive attention in regenerative medicine. To
      maintain the three-dimensional structure of natural extra cellular matrices in
      vitro, scaffolds can do this favor and mimic a microenvironment for cell
      proliferation and differentiation. According to previous studies, poly(lactic
      acid) and multi-wall carbon nanotubes have been introduced as novel and promising
      biomaterials for the proliferation and differentiation of stem cells. Some cell
      types have been successfully grown on a matrix containing carbon nanotubes in
      tissue engineering but there is no report for this material to support stem cells
      differentiation into germ cells lineage. This study designed a 3D wet-electrospun
      poly(lactic acid) and poly(lactic acid)/multi-wall carbon nanotubes composite
      scaffold to compare infiltration, proliferation, and differentiation potential of
      menstrual blood-derived stem cells toward germ cell lineage with 2D culture. Our
      primary data revealed that the fabricated scaffold has mechanical and biological
      suitable qualities for supporting and attachments of stem cells. The
      differentiated menstrual blood-derived stem cells tracking in scaffolds using
      scanning electron microscopy confirmed cell attachment, aggregation, and
      distribution on the porous scaffold. Based on the differentiation assay by RT-PCR
      analysis, stem cells and germ-like cells markers were expressed in 3D groups as
      well as 2D one. It seems that poly(lactic acid)/multi-wall carbon nanotubes
      scaffold-seeded menstrual blood-derived stem cells could be viewed as a novel,
      safe, and accessible construct for these cells, as they enhance germ-like
      generation from menstrual blood-derived stem cells.

PMID- 28752803
TI  - Designing and collecting data for a longitudinal study: the Sleman Health and
      Demographic Surveillance System (HDSS).
AB  - BACKGROUND: This paper describes the methodological considerations of developing
      an urban Health and Demographic Surveillance System (HDSS), in the Sleman
      District of Yogyakarta, Indonesia. METHODS: 1) The Sleman District was selected
      because it is mostly an urban area. 2) The minimum sample size was calculated to
      measure infant mortality as the key variable and resulted in a sample of 4942
      households. A two-stage cluster sampling procedure with probability proportionate
      to size was applied; first, 216 Censuses Blocks (CBs) were selected, and second,
      25 households in each CB were selected. 3) A baseline survey was started in 2015,
      and collected data on demographic and economic characteristics and verbal autopsy
      (VA); the 2nd cycle collected updated demographic data, VA, type of morbidity
      (communicable and non-communicable diseases, disability and injury) and health
      access. 4) The data were collected at a home visit through a Computer-Assisted
      Personal Interview (CAPI) on a tablet device, and the data were transferred to
      the server through the Internet. 5) The quality control consisted of spot-checks
      of 5% of interviews to control for adherence to the protocol, re-checks to ensure
      the validity of the interview, and computer-based data cleaning. 6) A utilization
      system was designed for policy-makers (government) and researchers. RESULTS: In
      total, 5147 households participated in the baseline assessment in 2015, and 4996
      households participated in the second cycle in 2016 (97.0% response rate).
      CONCLUSIONS: Development of an urban HDSS is possible and is beneficial in
      providing data complementary to the existing demographic and health information
      system at local, national and global levels.

PMID- 28752804
TI  - One-pot conjugated linoleic acid production from castor oil by Rhizopus oryzae
      lipase and resting cells of Lactobacillus plantarum.
AB  - Conjugated linoleic acid (CLA) has attracted as novel type of fatty acids having
      unusual health-promoting properties such as anticarcinogenic and antiobesitic
      effects. The present work employed castor oil as substrate for one-pot production
      of CLA using washed cells of Lactobacillus plantarum (L. plantarum) and lipases
      as catalysts. Among the screened lipases, the lipase Rhizopus oryzae (ROL)
      greatly assisted resting cells to produce CLA. Mass spectral analysis of the
      product showed that two major isomers of CLA were produced in the reaction
      mixture i.e. cis-9, trans-11 56.55% and trans-10, cis-12 43.45%. Optimum factors
      for CLA synthesis were found as substrate concentration (8 mg/mL), pH (6.5),
      washed cell concentration (12% w/v), and incubation time of 20 h. Hence, the
      combination of ROL with L. plantarum offers one pot production of CLA selectively
      using castor oil as a cost-effective substrate.

PMID- 28752805
TI  - Differences between Japan and Taiwan in the treatment of pregnant women with
      depressive symptoms by omega-3 fatty acids: An open-label pilot study.
AB  - OBJECTIVES: Although safe approaches for improving depression in pregnancy are
      required and the efficacy of omega-3 polyunsaturated fatty acids (PUFAs) has been
      suggested, the amount of supplemental omega-3 PUFAs has varied among previous
      studies and adequate amount might be different among countries. The aim of this
      pilot study is to explore the feasibility of using 1800 mg of omega-3 PUFAs
      supplementation for our future double-blind, placebo-control trial, and to
      clarify the clinical difference and the similarity between two sites of Japan and
      Taiwan. METHODS: Pregnant women between 12 and 24 weeks' gestation with
      depressive symptoms were recruited. Participants were supplemented daily with
      omega-3 PUFAs capsules containing 1206 mg eicosapentaenoic acid and 609 mg
      docosahexaenoic acid for 12 weeks. The primary outcome was change in total score
      on the 17-item Hamilton Rating Scale for Depression (HAMD) at 12 weeks after
      supplementation. RESULTS: Eight pregnant women in Japan and five in Taiwan
      participated in the study. A substantial proportion of pregnant women reported
      high consumption of omega-3 supplements and dietary fish were excluded in Taiwan
      rather than in Japan sites. The decrease in HAMD score from baseline to 12 weeks
      after the start of the intervention was significantly larger in Japanese
      participants than in Taiwanese participants (Wilcoxon rank sum test; P = 0.045).
      DISCUSSION: The improvement of depressive symptoms was smaller at the Taiwan site
      than at the Japan site. Differences in psychopathology of recruited participants
      identified by self-rating scales might affect the degree of population
      heterogeneity and the treatment efficacy. A randomized-controlled trial is needed
      to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01948596.

PMID- 28752806
TI  - The Influence of Social Interaction and Physical Health on the Association
      Between Hearing and Depression With Age and Gender.
AB  - Recent epidemiological data suggest the relation between hearing difficulty and
      depression is more evident in younger and middle-aged populations than in older
      adults. There are also suggestions that the relation may be more evident in
      specific subgroups; that is, other factors may influence a relationship between
      hearing and depression in different subgroups. Using cross-sectional data from
      the UK Biobank on 134,357 community-dwelling people and structural equation
      modelling, this study examined the potential mediating influence of social
      isolation and unemployment and the confounding influence of physical illness and
      cardiovascular conditions on the relation between a latent hearing variable and
      both a latent depressive episodes variable and a latent depressive symptoms
      variable. The models were stratified by age (40s, 50s, and 60s) and gender and
      further controlled for physical illness and professional support in associations
      involving social isolation and unemployment. The latent hearing variable was
      primarily defined by reported hearing difficulty in noise. For all subgroups,
      poor hearing was significantly related to both more depressive episodes and more
      depressive symptoms. In all models, the direct and generally small association
      exceeded the indirect associations via physical health and social interaction.
      Significant (depressive episodes) and near significant (depressive symptoms)
      higher direct associations were estimated for males in their 40s and 50s than for
      males in their 60s. There was at each age-group no significant difference in
      estimated associations across gender. Irrespective of the temporal order of
      variables, findings suggest that audiological services should facilitate
      psychosocial counselling.

PMID- 28752807
TI  - Objective Assessment of Listening Effort: Coregistration of Pupillometry and EEG.
AB  - Listening to speech in noise is effortful, particularly for people with hearing
      impairment. While it is known that effort is related to a complex interplay
      between bottom-up and top-down processes, the cognitive and neurophysiological
      mechanisms contributing to effortful listening remain unknown. Therefore, a
      reliable physiological measure to assess effort remains elusive. This study aimed
      to determine whether pupil dilation and alpha power change, two physiological
      measures suggested to index listening effort, assess similar processes. Listening
      effort was manipulated by parametrically varying spectral resolution (16- and 6
      channel noise vocoding) and speech reception thresholds (SRT; 50% and 80%) while
      19 young, normal-hearing adults performed a speech recognition task in noise.
      Results of off-line sentence scoring showed discrepancies between the target SRTs
      and the true performance obtained during the speech recognition task. For
      example, in the SRT80% condition, participants scored an average of 64.7%.
      Participants' true performance levels were therefore used for subsequent
      statistical modelling. Results showed that both measures appeared to be sensitive
      to changes in spectral resolution (channel vocoding), while pupil dilation only
      was also significantly related to their true performance levels (%) and task
      accuracy (i.e., whether the response was correctly or partially recalled). The
      two measures were not correlated, suggesting they each may reflect different
      cognitive processes involved in listening effort. This combination of findings
      contributes to a growing body of research aiming to develop an objective measure
      of listening effort.

PMID- 28752808
TI  - Decision-Making in Audiology: Balancing Evidence-Based Practice and Patient
      Centered Care.
AB  - Health-care service delivery models have evolved from a practitioner-centered
      approach toward a patient-centered ideal. Concurrently, increasing emphasis has
      been placed on the use of empirical evidence in decision-making to increase
      clinical accountability. The way in which clinicians use empirical evidence and
      client preferences to inform decision-making provides an insight into health-care
      delivery models utilized in clinical practice. The present study aimed to
      investigate the sources of information audiologists use when discussing
      rehabilitation choices with clients, and discuss the findings within the context
      of evidence-based practice and patient-centered care. To assess the changes that
      may have occurred over time, this study uses a questionnaire based on one of the
      few studies of decision-making behavior in audiologists, published in 1989. The
      present questionnaire was completed by 96 audiologists who attended the World
      Congress of Audiology in 2014. The responses were analyzed using qualitative and
      quantitative approaches. Results suggest that audiologists rank clinical test
      results and client preferences as the most important factors for decision-making.
      Discussion with colleagues or experts was also frequently reported as an
      important source influencing decision-making. Approximately 20% of audiologists
      mentioned utilizing research evidence to inform decision-making when no clear
      solution was available. Information shared at conferences was ranked low in terms
      of importance and reliability. This study highlights an increase in awareness of
      concepts associated with evidence-based practice and patient-centered care within
      audiology settings, consistent with current research-to-practice dissemination
      pathways. It also highlights that these pathways may not be sufficient for an
      effective clinical implementation of these practices.

PMID- 28752809
TI  - Psychosocial Development in 5-Year-Old Children With Hearing Loss Using Hearing
      Aids or Cochlear Implants.
AB  - This article reports on the psychosocial development and factors influencing
      outcomes of 5-year-old children with cochlear implants (CIs) or hearing aids
      (HAs). It further examines differences between children with CIs and HAs with
      similar levels of hearing loss. Data were collected as part of the Longitudinal
      Outcomes of Children with Hearing Impairment study-a prospective, population
      based study. Parents/caregivers of children completed the Strengths and
      Difficulties Questionnaire ( n = 333), the Social Skills subscale from the Child
      Development Inventory ( n = 317), and questionnaires on functional auditory
      behavior (Parents' Evaluation of Aural/oral performance of Children), and
      demographics. Children completed assessments of nonverbal cognitive ability
      (Wechsler Non-verbal Scale of Ability) and language (Preschool Language Scale -
      fourth edition). On average, parent-rated Strengths and Difficulties
      Questionnaire scores on emotional or behavioral difficulties were within 1 SD of
      the normative mean; however, Child Development Inventory scores on social skills
      were more than 1 SD below the norm. Children with severe-to-profound hearing
      losses using HAs had significantly more behavioral problems than children with
      CIs. Regression analyses showed that non-verbal cognitive ability, language, and
      functional auditory behavior were significantly associated with psychosocial
      outcomes for children with HAs, whereas outcomes for children with CIs were
      associated with functional auditory behavior and the presence of additional
      disabilities. Age at hearing intervention, severity of hearing loss, and
      communication mode were not associated with outcomes. The results suggest that
      even children who develop good language ability with the help of a HA or CI may
      have psychosocial problems if they exhibit difficulties with listening and
      communicating in everyday environments. The findings have implications for
      developing interventions for young children with hearing loss.

PMID- 28752810
TI  - Speech Recognition Outcomes After Cochlear Reimplantation Surgery.
AB  - This study compares speech recognition outcomes before and after cochlear
      reimplantation surgery, in relation to clinical factors known before and at time
      of surgery. Between 2006 and 2015, 2,055 adult cochlear implant surgeries were
      conducted at this center, of which 87 were reimplantation surgeries (4.2%).
      Speech recognition scores (SRS) assessed before and after reimplantation were
      available for 54 adults. Overall, SRS measured after reimplantation were similar
      to the best SRS obtained by the patient and greater than the last SRS measured
      before surgery. Additional complications were noted in the clinical files of all
      patients for which reimplantation was considered unsuccessful (16%).

PMID- 28752811
TI  - Bilateral Versus Unilateral Cochlear Implantation in Adult Listeners: Speech-On
      Speech Masking and Multitalker Localization.
AB  - Binaural hearing helps normal-hearing listeners localize sound sources and
      understand speech in noise. However, it is not fully understood how far this is
      the case for bilateral cochlear implant (CI) users. To determine the potential
      benefits of bilateral over unilateral CIs, speech comprehension thresholds (SCTs)
      were measured in seven Japanese bilateral CI recipients using Helen test
      sentences (translated into Japanese) in a two-talker speech interferer presented
      from the front (co-located with the target speech), ipsilateral to the first
      implanted ear (at +90 degrees  or -90 degrees ), and spatially symmetric at +/-90
      degrees . Spatial release from masking was calculated as the difference between
      co-located and spatially separated SCTs. Localization was assessed in the
      horizontal plane by presenting either male or female speech or both
      simultaneously. All measurements were performed bilaterally and unilaterally
      (with the first implanted ear) inside a loudspeaker array. Both SCTs and spatial
      release from masking were improved with bilateral CIs, demonstrating mean
      bilateral benefits of 7.5 dB in spatially asymmetric and 3 dB in spatially
      symmetric speech mixture. Localization performance varied strongly between
      subjects but was clearly improved with bilateral over unilateral CIs with the
      mean localization error reduced by 27 degrees . Surprisingly, adding a second
      talker had only a negligible effect on localization.

PMID- 28752812
TI  - Introducing the Australian Hearing Hub.
AB  - This special issue contains a collection of papers highlighting the collaborative
      research taking place at Macquarie University's Australian Hearing Hub. Included
      in this introduction is a brief outline of the challenges in the hearing health
      and communication space and a brief description of the Australian Hearing Hub and
      its members, alongside an overview of the studies included in this special issue.

PMID- 28752813
TI  - Fungal Recognition and Host Defense Mechanisms.
AB  - Fungi have emerged as premier opportunistic microbes of the 21st century, having
      a considerable impact on human morbidity and mortality. The huge increase in
      incidence of these diseases is largely due to the HIV pandemic and use of
      immunosuppressive therapies, underscoring the importance of the immune system in
      defense against fungi. This article will address how the mammalian immune system
      recognizes and mounts a defense against medically relevant fungal species.

PMID- 28752815
TI  - Regulatory Issues Associated with Preharvest Food Safety: United States
      Perspective.
AB  - The preharvest and preslaughter steps of food production constitute a first stage
      at which food can become contaminated with foodborne and toxigenic pathogens.
      Contamination at this early stage of food production can lead to amplification as
      food travels through the production and supply chain, accentuating the crucial
      need to address hazards and establish science-based metrics that are feasible to
      implement. This article discusses the preharvest food safety regulatory landscape
      in the United States, with a specific emphasis on fresh produce crops. Best
      practices, certification, audit schemes and challenges due to market channels,
      economies of scales, and grower behavior are considered in relation to the Food
      Safety Modernization Act. An outlook on the needs to facilitate implementation of
      the new law, develop educational programs for growers and stakeholders, and
      continue to better align food safety with environmental goals are presented.

PMID- 28752814
TI  - A Matter of Scale and Dimensions: Chromatin of Chromosome Landmarks in the Fungi.
AB  - Chromatin and chromosomes of fungi are highly diverse and dynamic, even within
      species. Much of what we know about histone modification enzymes, RNA
      interference, DNA methylation, and cell cycle control was first addressed in
      Saccharomyces cerevisiae, Schizosaccharomyces pombe, Aspergillus nidulans, and
      Neurospora crassa. Here, we examine the three landmark regions that are required
      for maintenance of stable chromosomes and their faithful inheritance, namely,
      origins of DNA replication, telomeres and centromeres. We summarize the state of
      recent chromatin research that explains what is required for normal function of
      these specialized chromosomal regions in different fungi, with an emphasis on the
      silencing mechanism associated with subtelomeric regions, initiated by sirtuin
      histone deacetylases and histone H3 lysine 27 (H3K27) methyltransferases. We
      explore mechanisms for the appearance of "accessory" or "conditionally
      dispensable" chromosomes and contrast what has been learned from studies on
      genome-wide chromosome conformation capture in S. cerevisiae, S. pombe, N.
      crassa, and Trichoderma reesei. While most of the current knowledge is based on
      work in a handful of genetically and biochemically tractable model organisms, we
      suggest where major knowledge gaps remain to be closed. Fungi will continue to
      serve as facile organisms to uncover the basic processes of life because they
      make excellent model organisms for genetics, biochemistry, cell biology, and
      evolutionary biology.

PMID- 28752817
TI  - Selection and Transmission of Antibiotic-Resistant Bacteria.
AB  - Ever since antibiotics were introduced into human and veterinary medicine to
      treat and prevent bacterial infections there has been a steady selection and
      increase in the frequency of antibiotic resistant bacteria. To be able to reduce
      the rate of resistance evolution, we need to understand how various biotic and
      abiotic factors interact to drive the complex processes of resistance emergence
      and transmission. We describe several of the fundamental factors that underlay
      resistance evolution, including rates and niches of emergence and persistence of
      resistant bacteria, time- and space-gradients of various selective agents, and
      rates and routes of transmission of resistant bacteria between humans, animals
      and other environments. Furthermore, we discuss the options available to reduce
      the rate of resistance evolution and/ or transmission and their advantages and
      disadvantages.

PMID- 28752816
TI  - Ploidy Variation in Fungi: Polyploidy, Aneuploidy, and Genome Evolution.
AB  - The ability of an organism to replicate and segregate its genome with high
      fidelity is vital to its survival and for the production of future generations.
      Errors in either of these steps (replication or segregation) can lead to a change
      in ploidy or chromosome number. While these drastic genome changes can be
      detrimental to the organism, resulting in decreased fitness, they can also
      provide increased fitness during periods of stress. A change in ploidy or
      chromosome number can fundamentally change how a cell senses and responds to its
      environment. Here, we discuss current ideas in fungal biology that illuminate how
      eukaryotic genome size variation can impact the organism at a cellular and
      evolutionary level. One of the most fascinating observations from the past 2
      decades of research is that some fungi have evolved the ability to tolerate large
      genome size changes and generate vast genomic heterogeneity without undergoing
      canonical meiosis.

PMID- 28752818
TI  - Fungal Diversity Revisited: 2.2 to 3.8 Million Species.
AB  - The question of how many species of Fungi there are has occasioned much
      speculation, with figures mostly posited from around half a million to 10
      million, and in one extreme case even a sizable portion of the spectacular number
      of 1 trillion. Here we examine new evidence from various sources to derive an
      updated estimate of global fungal diversity. The rates and patterns in the
      description of new species from the 1750s show no sign of approaching an
      asymptote and even accelerated in the 2010s after the advent of molecular
      approaches to species delimitation. Species recognition studies of (semi-)cryptic
      species hidden in morpho-species complexes suggest a weighted average ratio of
      about an order of magnitude for the number of species recognized after and before
      such studies. New evidence also comes from extrapolations of plant:fungus ratios,
      with information now being generated from environmental sequence studies,
      including comparisons of molecular and fieldwork data from the same sites. We
      further draw attention to undescribed species awaiting discovery in biodiversity
      hot spots in the tropics, little-explored habitats (such as lichen-inhabiting
      fungi), and material in collections awaiting study. We conclude that the commonly
      cited estimate of 1.5 million species is conservative and that the actual range
      is properly estimated at 2.2 to 3.8 million. With 120,000 currently accepted
      species, it appears that at best just 8%, and in the worst case scenario just 3%,
      are named so far. Improved estimates hinge particularly on reliable statistical
      and phylogenetic approaches to analyze the rapidly increasing amount of
      environmental sequence data.

PMID- 28752819
TI  - Computer assisted navigation in total knee and hip arthroplasty.
AB  - INTRODUCTION: Computer assisted surgery was pioneered in early 1990s. The first
      computer assisted surgery (CAS) total knee replacement with an imageless system
      was carried out in 1997. In the past 25 years, CAS has progressed from
      experimental in vitro studies to established in vivo surgical procedures.
      METHODS: A comprehensive body of evidence establishing the advantages of computer
      assisted surgery in knee and hip arthroplasty is available. Established benefits
      have been demonstrated including its role as an excellent research tool. Its
      advantages include dynamic pre-operative and per-operative assessment, increased
      accuracy in correction of deformities, kinematics and mechanical axis, a better
      alignment of components, better survival rates of prostheses and a better
      functional outcome. Adoption of computer navigation in the hip arthroplasty is
      still at an early stage compared to knee arthroplasty, though the results are
      well documented. Evidence suggests improved accuracy in acetabular orientation,
      positioning, hip offset and leg length correction. RESULTS: Among the orthopaedic
      surgeons, navigated knee arthroplasty is gaining popularity though slowly. The
      uptake rates vary from country to country. The Australian joint registry data
      shows increased navigated knee arthroplasty from 2.4% in 2003 to 28.6% in 2015
      and decreased revision rates with navigated knee arthroplasty in comparison with
      traditional instrumented knee arthroplasty in patient cohort under the age of 55
      years. CONCLUSION: Any new technology has a learning curve and with practice the
      navigation assisted knee and hip arthroplasty becomes easy. We have actively
      followed the evidence of CAS in orthopaedics and have successfully adopted it in
      our routine practice over the last decades. Despite the cautious inertia of
      orthopaedic surgeons to embrace CAS more readily; we are certain that computer
      technology has a pivotal role in lower limb arthroplasty. It will evolve to
      become a standard practice in the future in various forms like navigation or
      robotics.

PMID- 28752820
TI  - Variation in Preoperative Testing and Antireflux Surgery in Infants.
AB  - BACKGROUND: Despite the availability of objective tests, gastroesophageal reflux
      disease (GERD) diagnosis and management in infants remains controversial and
      highly variable. Our purpose was to characterize national variation in diagnostic
      testing and surgical utilization for infants with GERD. METHODS: Using the
      Pediatric Health Information System, we identified infants <1 year old diagnosed
      with GERD between January 2011 and March 2015. Outcomes included progression to
      antireflux surgery (ARS) and use of relevant diagnostic testing. By using
      adjusted generalized linear mixed models, we compared facility-level ARS
      utilization. RESULTS: Of 5 299 943 infants, 149 190 had GERD (2.9%), and 4518
      (3.0%) of those patients underwent ARS. Although annual rates of GERD and ARS
      decreased, there was a wide range of GERD diagnoses (1.8%-6.2%) and utilization
      of ARS (0.2%-11.2%). Facilities varied in the use of laparoscopic versus open ARS
      (mean: 66%, range: 23%-97%). Variation in facility-level ARS rates persisted
      after adjustment. Overall 3.8% of patients underwent diagnostic testing, whereas
      22.8% of ARS patients underwent diagnostic testing. The proportion of surgeries
      done laparoscopically was independently associated with ARS utilization (odds
      ratio: 1.57; 95% confidence interval: 1.21-2.02). Facility-level utilization of
      diagnostics (P > .1) and prevalence of GERD (P > .1) were not associated with
      utilization of ARS. CONCLUSIONS: There is notable variation in the overall
      utilization of ARS and in the surgical and diagnostic approach in infants with
      GERD. Fewer than 4% of infants with GERD undergo diagnostic testing. This
      variation in care merits development of consensus guidelines and further
      research.

PMID- 28752821
TI  - Lotus-on-chip: computer-aided design and 3D direct laser writing of bioinspired
      surfaces for controlling the wettability of materials and devices.
AB  - In this study we present the combination of a math-based design strategy with
      direct laser writing as high-precision technology for promoting solid free-form
      fabrication of multi-scale biomimetic surfaces. Results show a remarkable control
      of surface topography and wettability properties. Different examples of surfaces
      inspired on the lotus leaf, which to our knowledge are obtained for the first
      time following a computer-aided design with this degree of precision, are
      presented. Design and manufacturing strategies towards microfluidic systems whose
      fluid driving capabilities are obtained just by promoting a design-controlled
      wettability of their surfaces, are also discussed and illustrated by means of
      conceptual proofs. According to our experience, the synergies between the
      presented computer-aided design strategy and the capabilities of direct laser
      writing, supported by innovative writing strategies to promote final size while
      maintaining high precision, constitute a relevant step forward towards materials
      and devices with design-controlled multi-scale and micro-structured surfaces for
      advanced functionalities. To our knowledge, the surface geometry of the lotus
      leaf, which has relevant industrial applications thanks to its hydrophobic and
      self-cleaning behavior, has not yet been adequately modeled and manufactured in
      an additive way with the degree of precision that we present here.

PMID- 28752822
TI  - Machine learning and genetic algorithm prediction of energy differences between
      electronic calculations of graphene nanoflakes.
AB  - Computational screening is key to understanding structure-function relationships
      at the nanoscale but the high computational cost of accurate electronic structure
      calculations remains a bottleneck for the screening of large nanomaterial
      libraries. In this work we propose a data-driven strategy to predict accuracy
      differences between different levels of theory. Machine learning (ML) models are
      trained with structural features of graphene nanoflakes to predict the
      differences between electronic properties at two levels of approximation. The ML
      models yield an overall accuracy of 94% and 88%, for energy of the Fermi level
      and the band gap, respectively. This strategy represents a successful application
      of established ML methods to the selection of optimum level of theory, enabling
      more rapid and efficient screening of nanomaterials, and is extensible to other
      materials and computational methods.

PMID- 28752823
TI  - Prospects and applications near ferroelectric quantum phase transitions: a key
      issues review.
AB  - The emergence of complex and fascinating states of quantum matter in the
      neighborhood of zero temperature phase transitions suggests that such quantum
      phenomena should be studied in a variety of settings. Advanced technologies of
      the future may be fabricated from materials where the cooperative behavior of
      charge, spin and current can be manipulated at cryogenic temperatures. The
      progagating lattice dynamics of displacive ferroelectrics make them appealing for
      the study of quantum critical phenomena that is characterized by both space- and
      time-dependent quantities. In this key issues article we aim to provide a self
      contained overview of ferroelectrics near quantum phase transitions. Unlike most
      magnetic cases, the ferroelectric quantum critical point can be tuned
      experimentally to reside at, above or below its upper critical dimension; this
      feature allows for detailed interplay between experiment and theory using both
      scaling and self-consistent field models. Empirically the sensitivity of the
      ferroelectric T c's to external and to chemical pressure gives practical access
      to a broad range of temperature behavior over several hundreds of Kelvin.
      Additional degrees of freedom like charge and spin can be added and characterized
      systematically. Satellite memories, electrocaloric cooling and low-loss phased
      array radar are among possible applications of low-temperature ferroelectrics. We
      end with open questions for future research that include textured polarization
      states and unusual forms of superconductivity that remain to be understood
      theoretically.

PMID- 28752824
TI  - The feasibility of in vivo detection of lanthanum using a 241Am K x-ray
      fluorescence system.
AB  - OBJECTIVE: Lanthanum (La) is commonly used in phosphate binders in the form of
      lanthanum carbonate in patients with end-stage kidney disease undergoing
      hemodialysis treatments. With this administration, there is the potential for La
      storage in the body with bone being the main site of concern. However, the long
      term effects of residual La in the body on bone health are not yet known. In this
      work, we investigate the feasibility of using a K x-ray fluorescence (K-XRF)
      spectroscopy system to measure bone La in vivo. APPROACH: A series of
      hydroxyapatite (HAp) bone mineral phantoms were created to represent human bone.
      A 1.09 GBq 241Am source was used to excite the HAp phantoms doped with various
      known concentrations of La placed in a 90 degrees  geometry relative to the
      photon source and high-purity germanium (HPGe) detector. MAIN RESULTS: For a
      detector live time of 2000 s, the minimum detection limit was calculated to be
      1.7 ug La g-1 Ca or 0.7 ug La g-1 HAp and is comparable to previously reported in
      vivo bone La concentrations. SIGNIFICANCE: The technique developed in this study
      shows promising results and provides an alternative method to invasive biopsy
      sampling techniques to monitor the accumulation of bone La. To the best of our
      knowledge, this is the first reported work that seeks to non-invasively measure
      bone La via in vivo XRF.

PMID- 28752825
TI  - DC biased low-frequency insulating constriction dielectrophoresis for protein
      biomolecules concentration.
AB  - Sample enrichment or molecules concentration is considered an essential step in
      sample processing of miniaturized devices aimed at biosensing and bioanalysis.
      Among all the means involved to achieve this aim, dielectrophoresis (DEP) is
      increasingly employed in molecules manipulation and concentration because it is
      non-destructive and high efficiency. This paper presents a methodology to achieve
      protein concentration utilizing the combination effects of electrokinetics and
      low frequency insulating dielectrophoresis (iDEP) generated within a microfluidic
      device, in which a submicron constricted channel was fabricated using DNA
      molecular combing and replica molding. This fabrication technique avoids using e
      beam lithography or other complicated nanochannel fabrication methods, and
      provides an easy and low cost approach with the flexibility of controlling
      channel dimensions to create highly constricted channels embedded in a
      microfluidic device. With theoretical analysis and experiments, we demonstrated
      that fluorescein isothiocyanate conjugated bovine serum albumin (FITC-BSA)
      protein molecules can be significantly concentrated to form an arc-shaped band
      near the constricted channel under the effects of a negative dielectrophoretic
      force and DC electrokinetic forces within a short period of time. It was also
      observed that the amplitudes of the applied DC and AC electric fields, the AC
      frequencies as well as the suspending medium conductivities had strong effects on
      the concentration responses of the FITC-BSA molecules, including the concentrated
      area and position, intensities of the focused molecules, and concentration speed.
      Our method provides a simple and flexible approach for quickly concentrating
      protein molecules by controlling the applied electric field parameters. The iDEP
      device reported in this paper can be used as a stand-alone sensor or worked as a
      pre-concentration module integrated with biosensors for protein biomarker
      detection. Furthermore, low frequency dielectrophoresis provides practical uses
      for integrating the concentration module with a portable biosensing system.

PMID- 28752826
TI  - Realization of wide circadian variability by quantum dots-luminescent mesoporous
      silica-based white light-emitting diodes.
AB  - Human comfort has become one of the most important criteria in modern lighting
      architecture. Here, we proposed a tuning strategy to enhance the non-image
      forming photobiological effect on the human circadian rhythm based on quantum
      dots-converted white light-emitting diodes (QDs-WLEDs). We introduced the
      limiting variability of the circadian action factor (CAF), defined as the ratio
      of circadian efficiency and luminous efficiency of radiation. The CAF was deeply
      discussed and was found to be a function of constraining the color rendering
      index (CRI) and correlated color temperatures. The maximum CAF variability of QDs
      WLEDs was found to be dependent on the QDs' peak wavelength and full width at
      half maximum. With the optimized parameters, the packaging materials were
      synthesized and WLEDs were packaged. Experimental results show that at CRI > 90,
      the maximum CAF variability can be tuned by 3.83 times (from 0.251 at 2700 K to
      0.961 at 6500 K), which implies that our approach could reduce the number of
      tunable channels, and could achieve wider CAF variability.

PMID- 28752827
TI  - Clinical pathway for patients with Chronic Myeloid Leukaemia: The Euriclea
      Project.
AB  - BACKGROUND AND AIMS: The use of Tirosine Kinase Ihnibitors (TKIs) for the
      treatment of Chronic Myeloid Leukemia (CML) has definitely represented a turning
      point in the treatment of the onco-hematological diseases. Over the years, the
      interest of physicians, nurses, patients and caregivers has increasingly focused
      on the aspects of the humanization of care, the management of side effects and on
      the full and constant therapeutic adherence. The aim of the project was to define
      patient-oriented care processes, based on a proactive approach that can fully
      respond to the new health needs of CML patients. METHODS: A nursing expert
      Working Group (WG) was established. WG reviewed literature about CML patients
      assistance and then it was conducted a survey on organizational models for the
      treatment of CML patients, adopted by Italian haematologic and transplant
      centers.  Finally, the main issues regarding CML patients care were identified
      and discussed on a multiprofessional basis. RESULTS: Euriclea Project for care of
      CML patients with the description of a new and expanded nurse role was defined.
      The Nurse Case Manager or Nursing Clinical Experts were identified as key people
      for the management of the side effects of treatment, the promotion of the
      therapeutic adherence and the evaluation of efficacy and effectiveness of the
      process through the identification of specific indicators for structure, process
      and outcome. DISCUSSION: The focal areas of the care process were identified so
      as to define a different approach to the CML patient, through a holistic view of
      care and the multidisciplinary interventions.

PMID- 28752828
TI  - Integrated narrative assessment exemplification: a leukaemia case history.
AB  - BACKGROUND AND AIM: In the Integrated Narrative Nursing Assessment (INNA), the
      Evidence-Based Nursing Model is integrated with the Narrative-Based Nursing
      Model. The INNA makes use of quantitative instruments, arising from the natural
      sciences as well as of qualitative ones, arising from the human achieving results
      of standardization and reproducibility, as well as of customization and
      uniqueness. Accordingly, the purpose of this work is to exemplify the thinking
      process of and the method adopted by a nurse adopting an integrated narrative
      assessment in the evaluation of a patient. METHOD: The patient suffered from
      acute myeloid leukaemia, treated with chemotherapy. Her nurse worked in a
      haematology ward in a North Italy Hospital. The nurse had previous experience in
      conducting the assessment according to INNA. Based on patient's characteristics,
      the nurse chose to use the narration (to explore needs from their subjective
      perception) and the scales (to measure them objectively) among the various
      assessment instruments provided by the INNA. RESULTS: The resultant integrated
      outcomes helped the nurse to have a comprehensive overview of the person's health
      care needs and their connections. These outcomes derive from the integration of
      narrative information with those obtained from the scales, which in this paper
      have shown consistent results. CONCLUSION: It is very difficult to reach this
      complexity by considering qualitative and quantitative assessment strategies as
      mutually foreclosing, given that both emerged as being very useful in
      identifying, understanding and measuring the needs of the assisted person. Then
      they both could be used to design a customized intervention, encouraging new
      connections between disease, illness, sickness and everyday life.

PMID- 28752829
TI  - Empathic attitudes among nursing students: a preliminary study.
AB  - BACKGROUND AND AIM: An empathic approach is fundamental for therapeutic
      relationship between nurse and patient. According to some researchers, female
      nursing students show higher empathic attitude in comparison with males, but both
      show a decline in empathy level as their studies progress. This preliminary study
      evaluated the self-reported emotional empathy level among undergraduate students
      at first and second year of nursing 3-year course. METHOD: To assess empathy
      level, the Balanced Emotional Empathy Scale (BEES) was administered to all
      students enrolled in the 2015/16 academic year (N=142), at the beginning of first
      year (T0) and at mid-point of second year (T1) of nursing course. Data were
      statistically analyzed. RESULTS: 118 nursing students participated in the first
      and 99 in the second survey. The BEES global mean score for the longitudinal
      group (n=99) slightly decreased  from T0 (mean=37.1+/-19.5 SD) to T1 (mean=33.5+/
      22.6 SD) (t=1.20, p=0.23; t-test for paired data). Female students reported a
      statistically significant higher mean BEES score compared to male students in
      both surveys. CONCLUSIONS: Our preliminary data suggest a slight decline in
      empathy level among nursing students with the progress of study course, in
      accordance with  previous studies. In particular, our study shows higher levels
      of empathy in female students and lower levels in male students, compared to
      other studies.  Further surveys aimed at investigating the empathy attitude at
      the end of nursing course could confirm the decline tendency reported by this
      preliminary study. Other research focusing on the causes of empathy decline are
      necessary to explain this phenomenon.

PMID- 28752830
TI  - Healthcare associated infection: good practices, knowledge and the locus of
      control in heatlhcare professionals.
AB  - BACKGROUND AND AIM: The incidence of Healthcare Associated Infections (HAI) is an
      important indicator of the quality of care. The behaviors associated with the
      prevention of infections are not only supported by rational knowledge or
      motivation, but are mediated by social, emotional and often stereotyped
      behaviors. The awarness of the good practices related to HAI, may be a factor.
      Other studies, identify how the perception of the problem in healthcare
      professionals is often influenced by a tendency towards an external Locus of
      Control: the patient, the family, the other wards, other care settings. The aim
      of this study is to investigate the perception of healthcare professionals. In
      particular they have been measured their  awarness of the good practices,
      perceptions of the potential contamination level of some commonly used objects,
      knowledge about the management of invasive devices, Locus of Control. METHOD: A
      cross-sectional correlational design was utilized.  An ad hoc questionnaire was
      interviewed by 222 health professionals nurses and physicians in a northern
      hospital of Italy. RESULTS: The percentage of professionals who have attended
      training courses over the last 5 years was quite high, both for upgrades on HAI
      (78.7%) and Vascular Catheters (78.8%), while the percentage of professionals who
      updated on bladder catheterization (59.46%) was lower. The mean  score of good
      practice awareness towards HAI (5.06), is high. The perception of the potential
      level of contamination of some devices had a  mean ranging from 4.62 (for the
      drip) to 5.26 (for the door handle). The average value of the Locus of Control
      (43.54) indicates that participants demonstrated a value that is midway between
      External and Internal. The correlation test analysis revealed no significant
      relationships among professionals'age, knowledge about HAI, or infection related
      venus catheter. Also, results revealed that there were statistically significant
      positive relationships between professionals' Good Practices awareness about HAI
      , Knowledge, and Locus of Control. CONCLUSION: The study findings demonstrated
      that good practice awareness towards HAI among nurse and physician was good but
      not completely optimal. Findings revealed that knowledge toward HAI prevention
      and HAI related device prevention were not completely adequate. The educational
      courses, according to our correlational findings, should definitely take into
      account the psycho-social aspects of this phenomenon.

PMID- 28752831
TI  - Intergroup contact and team functioning among nursing students: the mediation
      role of intergroup anxiety.
AB  - BACKGROUND AND AIM:  BACKGROUND AND AIM OF THE WORK: The improvement of team
      effectivity is one of the main concerns for healthcare organizations. Moreover,
      healthcare organizations must cope with increasing multicultural composition of
      both workforce and patients. The intergroup contact theory suggests that frequent
      and positive face-to-face contact among professionals or students with different
      cultural heritage can help to reach both increasing team effectiveness and
      adequate care in a multicultural setting. The aim was then to verify whether
      intergroup contact during practical training would decrease intergroup anxiety
      and then increase team functioning. METHODS: A cross-sectional design was used in
      which a questionnaire was delivered to 83 nursing students. RESULTS: According to
      the intergroup contact theory, frequent and positive contact with non-native
      professionals decreased the intergroup anxiety which, in turn, increased
      prejudice and, more importantly, decreased team functioning. Moreover, intergroup
      anxiety showed a complete mediation effect on the relations between intergroup
      contact during practical training and both negative attitude toward immigrants
      and team functioning. CONCLUSIONS: Intergroup contact with non-native
      professionals or students during practical training is able to indirectly
      decrease prejudice and improve team functioning by lowering the anxiety that is
      aroused by encounter with non-native individuals.

PMID- 28752832
TI  - Lack of respect, role uncertainty and satisfaction with clinical practice among
      nursing students: the moderating role of supportive staff.
AB  - BACKGROUND AND AIMS: Clinical learning placements provide a real-world context
      where nursing students can acquire clinical skills and the attitudes that are the
      hallmark of the nursing profession. Nonetheless, nursing students often report
      dissatisfaction with their clinical placements. The aim of this study was to test
      a model of the relationship between student's perceived respect, role
      uncertainty, staff support, and satisfaction with clinical practice. METHOD: A
      cross-sectional, descriptive survey was completed by 278 second- and third-year
      undergraduate nursing students. Specifically, we tested the moderating role of
      supportive staff and the mediating role of role uncertainty. RESULTS: We found
      that lack of respect was positively related to role uncertainty, and this
      relationship was moderated by supportive staff, especially at lower levels. Also,
      role uncertainty was a mediator of the relationship between lack of respect and
      internship satisfaction; lack of respect increased role uncertainty, which in
      turn was related to minor satisfaction with clinical practice. CONCLUSION: This
      study explored the experience of nursing students during their clinical learning
      placements. Unhealthy placement environments, characterized by lack of respect,
      trust, and support increase nursing students' psychosocial risks, thus reducing
      their satisfaction with their clinical placements. Due to the current global
      nursing shortage, our results may have important implications for graduate
      recruitment, retention of young nurses, and professional progression.

PMID- 28752833
TI  - Mapping the nursing competences in neonatology: a qualitative research.
AB  - BACKGROUND AND AIM: There are several studies that support the importance of
      advanced expertise and specialization of the neonatal pediatric nurse. However,
      proceeding with a analysis of the scientific literature regarding the nursing
      advanced competence in neonatology, very few studies specify and define these
      competences. The aim of the study is investigate and analyze skills, tasks and
      responsibilities of the neonatal pediatric nurse, to map a "neonatal nurse
      competence profile", offered from the points of view of the Neonatology Units
      professionals. METHODS: 32 professionals (nurses, physicians, psychologists,
      healthcare assistants) operating in the Neonatal Intensive Care Unit of two
      Italian Hospitals were interviewed. The semi-structured interviews have been
      performed, transcribed and analyzed following the Levati's model (based on
      Activity, Expectations and Evaluation system). RESULTS: About the nurses
      activities, the participants underlined the newborn care, the care of the
      caregiver and the "bureaucratic" activities. About the system of expectations,
      the participants marked on specific skills but those are described only
      comprehensively. About the evaluation system there are different perceptions
      among the professionals, but the nurses themselves feel that they have to answer
      for their actions primarily to infants and families, indicating a sense of
      responsibility towards the patients. CONCLUSIONS: On the basis of the interviews
      a profile of a neonatal nurse competences has been drawn up. This consists of 42
      competences that future studies can further specify, integrate and expand.

PMID- 28752834
TI  - Individual and social variables and their effect on Case/Care Manager Job
      Satisfaction: an exploratory study.
AB  - BACKGROUND AND AIMS: The Case/Care Manager (CCM) is a new position for in the
      Italian National Health Service scenario. Job satisfaction plays a key role for
      the CCM to engage in his work, accomplishing it in a complete. Nurses' job
      satisfaction is a complex construct and many different variables can influence
      it: personal characteristics, cultural characteristic, social characteristic,
      organizational characteristic, and environmental characteristic. The main aim of
      this study is to assess the job satisfaction in a sample of CCM and to assess if
      and how Social Variables (organizational climate and health) and Individual
      (socio-demographic variables, coping strategies, emotion regulation) relate to
      the CCM job satisfaction. METHODS: This study has a quantitative exploratory
      cross-sectional design. Participants were Nurse CCM with or without specific
      training who filled a battery of questionnaires : Job Satisfaction Survey (JSS) ,
      section three of ICONAS questionnaire, section five of the Multidimensional
      Organizational Health Questionnaire (MOHQ), anamnestic sheet, Coping Orientation
      to the Problems Experienced (COPE-NVI-25), and Emotion Regulation Questionnaire
      (ERQ). The battery was administered online on the website of Italian Case
      Manager, Italian Association of Care Manager, and IPASVI Colleges. It was also
      distributed during the National Congress for Case Manager in Padua. RESULTS: 103
      participants took part in the study. The total mean score of JSS was 117,28
      (S.D.=21,12). The emotional regulation strategy most used was the "Cognitive
      Response", and the most used Coping strategy was "Problem Oriented". There were
      significant correlations between JSS and Social variables in the total score
      (ICONAS r=.574 p<0.01; MOHQ (positive indicators) r=.608 p<0.01; MOHQ (negative
      indicators) r=-.634 p <0.01) and in its subscales. There were also significant
      correlations between JSS subscales and Individual variables (COPE and ERQ).
      Participants with a specific training tend to use the emotion regulation strategy
      "Negative interpretation self-oriented" (U 910.500 p<0.005) and "Distraction" (U
      885.000 p<0.005) more than those without specific training. The same significant
      difference was found in JSS pay (t=-2,48 per p<0.05) and JSS Fringe Benefits (t=
      2,07 per p<0.05). DISCUSSION: The CCM job satisfaction seems to be ambivalent. It
      seems to be not entirely polarized on presence/absence, but rather still in a
      gray area. organizational climate and health influence significantly the overall
      perception of job satisfaction and its different areas. The most "avoiding"
      emotional regulation strategies, seem to negatively affect the perception of
      satisfaction. Emotional regulation and coping strategies related to challenges
      focusing and management, along with the individual perception of collaboration,
      positively influence satisfaction. Participants who underwent a specific CCM
      training, committing themselves financially and personally, perceive less job
      satisfaction when their role is not recognized in terms of pay. This study showed
      that that the main strategies used to regulate emotions are the Cognitive
      Response and the Social Contact. We suggest that further studies could be made to
      define the links between individual strategies and the presence of chronic
      distress and we suggest that a specific training on coping and emotion regulation
      may be implemented in graduation and post-graduation courses.

PMID- 28752835
TI  - Advanced competencies mapping of critical care nursing: a qualitative research in
      two Intensive Care Units.
AB  - BACKGROUND AND AIM: Nowadays, in Italy, the nursing profession has suffered
      important changes in response to the needs of citizens' health and to improve the
      quality of the health service in the country.  At the basis of this development
      there is an increase of the nurses' knowledge, competencies and responsibilities.
      Currently, the presence of nurses who have followed post-basic training paths,
      and the subsequent acquisition of advanced clinical knowledge and
      specializations, has made it essential for the presence of competencies mappings
      for each specialty, also to differentiate them from general care nurses. The
      objective is to get a mapping of nurse's individual competencies working in
      critical care, to analyze the context of the Parma Hospital and comparing it with
      the Lebanon Heart Hospital in Lebanon. METHOD: The survey has been done through a
      series of interviews involving some of the hospital staff, in order to collect
      opinions about the ICU nurses' competencies. RESULTS: What emerged from the data
      allowed us to get a list of important abilities, competencies, character traits
      and  intensive care nurse activities. Italians and Lebanese nurses appear to be
      prepared from a technical point of view, with a desire for improvement through
      specializations, masters and enabling courses in advanced health maneuvers. By
      respondents nurses can seize a strong desire for professional improvement.
      CONCLUSIONS: At the end of our research we were able to draw a list of different
      individual competencies, behavioral and moral characteristics. The nurse figure
      has a high potential and large professional improvement prospects, if more taken
      into account by the health system.

PMID- 28752836
TI  - Corrigendum: Large-scale production of megakaryocytes from human pluripotent stem
      cells by chemically defined forward programming.
AB  - This corrects the article DOI: 10.1038/ncomms11208.

PMID- 28752837
TI  - An international comparison of retinopathy of prematurity grading performance
      within the Benefits of Oxygen Saturation Targeting II trials.
AB  - PurposeTo investigate whether the observed international differences in
      retinopathy of prematurity (ROP) treatment rates within the Benefits of Oxygen
      Saturation Targeting (BOOST) II trials might have been caused by international
      variation in ROP disease grading.MethodsGroups of BOOST II trial ophthalmologists
      in UK, Australia, and New Zealand (ANZ), and an international reference group
      (INT) used a web based system to grade a selection of RetCam images of ROP
      acquired during the BOOST II UK trial. Rates of decisions to treat, plus disease
      grading, ROP stage grading, ROP zone grading, inter-observer variation within
      groups and intra-observer variation within groups were measured.ResultsForty-two
      eye examinations were graded. UK ophthalmologists diagnosed treat-requiring ROP
      more frequently than ANZ ophthalmologists, 13.9 (3.49) compared to 9.4 (4.46) eye
      examinations, P=0.038. UK ophthalmologists diagnosed plus disease more frequently
      than ANZ ophthalmologists, 14.1 (6.23) compared to 8.5 (3.24) eye examinations,
      P=0.021. ANZ ophthalmologists diagnosed stage 2 ROP more frequently than UK
      ophthalmologists, 20.2 (5.8) compared to 12.7 (7.1) eye examinations, P=0.026.
      There were no other significant differences in the grading of ROP stage or zone.
      Inter-observer variation was higher within the UK group than within the ANZ
      group. Intra-observer variation was low in both groups.ConclusionsWe have found
      evidence of international variation in the diagnosis of treatment-requiring ROP.
      Improved standardisation of the diagnosis of treatment-requiring ROP is required.
      Measures might include improved training in the grading of ROP, using an
      international approach, and further development of ROP image analysis software.

PMID- 28752838
TI  - Sessile serrated adenomas with dysplasia: morphological patterns and correlations
      with MLH1 immunohistochemistry.
AB  - Sessile serrated adenomas are the precursor polyp of approximately 20% of
      colorectal carcinomas. Sessile serrated adenomas with dysplasia are rarely
      encountered and represent an intermediate step to malignant progression,
      frequently associated with loss of MLH1 expression. Accurate diagnosis of these
      lesions is important to facilitate appropriate surveillance, particularly because
      progression from dysplasia to carcinoma can be rapid. The current World Health
      Organization classification describes two main patterns of dysplasia occurring in
      sessile serrated adenomas, namely, serrated and conventional. However, this may
      not adequately reflect the spectrum of changes seen by pathologists in routine
      practice. Furthermore, subtle patterns of dysplasia that are nevertheless
      associated with loss of MLH1 expression are not encompassed in this
      classification. We performed a morphological analysis of 266 sessile serrated
      adenomas with dysplasia with concurrent MLH1 immunohistochemistry with the aims
      of better defining the spectrum of dysplasia occurring in these lesions and
      correlating dysplasia patterns with MLH1 expression. We found that dysplasia can
      be divided morphologically into four major patterns, comprising minimal deviation
      (19%), serrated (12%), adenomatous (8%) and not otherwise specified (79%) groups.
      Minimal deviation dysplasia is defined by minor architectural and cytological
      changes that typically requires loss of MLH1 immunohistochemical expression to
      support the diagnosis. Serrated dysplasia and adenomatous dysplasia have
      distinctive histological features and are less frequently associated with loss of
      MLH1 expression (13 and 5%, respectively). Finally, dysplasia not otherwise
      specified encompasses most cases and shows a diverse range of morphological
      changes that do not fall into the other subgroups and are frequently associated
      with loss of MLH1 expression (83%). This morphological classification of sessile
      serrated adenomas with dysplasia may represent an improvement on the current
      description as it correlates with the underlying mismatch repair protein status
      of the polyps and better highlights the range of morphologies seen by
      pathologists.

PMID- 28752839
TI  - Development and validation of a novel clinical fluorescence in situ hybridization
      assay to detect JAK2 and PD-L1 amplification: a fluorescence in situ
      hybridization assay for JAK2 and PD-L1 amplification.
AB  - The amplification of chromosome 9p24.1 encoding PD-L1, PD-L2, and JAK2 has been
      reported in multiple types of cancer and is associated with poor outcome,
      upregulation of PD-L1, and activation of the JAK/STAT pathway. We have developed
      a novel fluorescence in situ hybridization assay which combines 3 probes mapping
      to 9p24.1 with a commercial chromosome 9 centromere (CEN9) probe for detection of
      the JAK2/9p24.1 amplification. JAK2 fluorescence in situ hybridization was
      compared with array-based comparative genomic hybridization in 34 samples of
      triple negative breast cancer tumor. By array-based comparative genomic
      hybridization, 15 had 9p24.1 copy-number gain (log2ratio>0.3) and 19 were
      classified as non-gain (log2ratio<=0.3). Copy-number gain was defined as
      JAK2/CEN9 ratio >=1.1 or average JAK2 signals>=3.0. Twelve of 15 samples with
      copy-number gain by array-based comparative genomic hybridization were also
      detected by fluorescence in situ hybridization. Eighteen of 19 samples classified
      as copy-number non-gain by array-based comparative genomic hybridization were
      concordant by array-based comparative genomic hybridization. The sensitivity and
      specificity of the fluorescence in situ hybridization assay was 80% and 95%,
      respectively (P=0.02). The sample with the highest level of amplification by
      array-based comparative genomic hybridization (log2ratio=3.6) also scored highest
      by fluorescence in situ hybridization (ratio=8.2). There was a correlation
      between the expression of JAK2 and amplification status (Mean 633 vs 393,
      P=0.02), and there was a trend of association with PD-L1 RNA expression (Mean 46
      vs 22, P=0.11). No significant association was observed between PD-L1
      immunohistochemistry expression and copy-number gain status. In summary, the
      novel array-based comparative genomic hybridization assay for detection of
      chromosome 9p24.1 strongly correlates with the detection of copy-number gain by
      array-based comparative genomic hybridization. In triple negative breast cancer,
      this biomarker may identify a relevant subset of patients for targeted molecular
      therapies.

PMID- 28752840
TI  - Genetic evaluation of juvenile xanthogranuloma: genomic abnormalities are
      uncommon in solitary lesions, advanced cases may show more complexity.
AB  - Juvenile xanthogranuloma is a rare histiocytic proliferation primarily affecting
      infants and young children, characterized by aberrant infiltration of histiocyte
      derived cells in the skin, soft tissues and more rarely, visceral organs.
      Juvenile xanthogranuloma is generally considered to be a benign disorder; most
      lesions are solitary cutaneous nodules that resolve spontaneously without
      treatment. However, cases with extracutaneous involvement, multiple lesions,
      and/or systemic disease often require aggressive therapy. Though molecular
      studies have provided evidence of clonality in juvenile xanthogranuloma, in
      support of a neoplastic process, little is known about the genetic profile of
      juvenile xanthogranuloma. We used molecular inversion probe array technology to
      evaluate the genomic characteristics (copy number alterations or copy neutral
      loss of heterozygosity) of 21 archived cases of juvenile xanthogranuloma (19
      solitary, 1 diffuse cutaneous, 1 systemic). Four cases (19%) showed acquired,
      clonal alterations. Two lesions from a case of diffuse cutaneous juvenile
      xanthogranuloma showed distinct profiles: JXG-1a contained trisomy 5 and 17 and
      JXG-1b contained loss of heterozygosity in 5q. The systemic juvenile
      xanthogranuloma (JXG-2) showed multiple genomic alterations. Only two of 19
      solitary juvenile xanthogranulomas showed abnormal genomic profiles: JXG-3 showed
      gains on 1q and 11q and JXG-4 showed a 7.2 Mb loss in 3p. No recurrent
      abnormalities were observed among these cases. The presence of non-recurrent copy
      number alterations in a subset of samples implies that copy number changes are
      unlikely driving pathogenesis in juvenile xanthogranuloma, but may be acquired
      during disease progression. The presence of genomic abnormalities in more
      advanced cases (ie, systemic and diffuse cutaneous juvenile xanthogranuloma)
      supports this notion, particularly as the advanced cases of juvenile
      xanthogranuloma presented more genomic complexity.

PMID- 28752841
TI  - HER2 immunohistochemical and fluorescence in situ hybridization discordances in
      invasive breast carcinoma with micropapillary features.
AB  - The 2013 American Society of Clinical Oncology/College of American Pathologists
      (ASCO/CAP) recommendations for HER2 testing contain a recommendation for
      pathologists with respect to invasive micropapillary carcinoma. The guidelines
      suggest that HER2 immunohistochemical staining that is intense but incomplete and
      would be considered 1+ may actually be HER2-amplified by fluorescence in situ
      hybridization. Thus, pathologists should consider reporting the
      immunohistochemistry as equivocal (2+) and employ an alternative testing
      methodology. This recommendation is based largely on one paper wherein the
      authors tested a series of 22 micropapillary carcinomas that were considered 1+
      by immunohistochemistry and identified HER2 amplification in one case (5%). In
      order to assess for a possible discordance between HER2 immunohistochemistry and
      fluorescence in situ hybridization, we evaluated a series of invasive carcinomas
      with micropapillary features using both methodologies. As described by the WHO,
      invasive carcinomas with micropapillary features have small, hollow, or morula
      like clusters of cells surrounded by clear stromal spaces. All cases had HER2
      immunohistochemistry and fluorescence in situ hybridization performed, and for
      cases with equivocal fluorescence in situ hybridization results, an alternative
      Chromosome 17 probe (RAI1) was employed. All assays were scored according to the
      2013 ASCO/CAP guidelines. Specifically for this study, immunohistochemistry was
      scored irrespective of the presence of micropapillary features. Overall, we
      identified HER2 amplification in 21 (47%) of the cases assayed, with the
      corresponding immunohistochemistry being 1+ (n=9), 2+ (n=11), and 3+ (n=1). The
      ASCO/CAP recommendation that this morphology may deviate from the typical
      staining pattern is highlighted, as we found that 43% of cases with
      micropapillary features and HER2 staining that would otherwise be scored as 1+
      were HER2-amplified by fluorescence in situ hybridization. This study supports
      the ASCO/CAP recommendation that pathologists should consider reporting
      immunohistochemistry in this morphology as equivocal and perform reflex testing
      using in situ hybridization.

PMID- 28752842
TI  - USP6 activation in nodular fasciitis by promoter-swapping gene fusions.
AB  - Nodular fasciitis is a self-limited myofibroblastic lesion that can be
      misdiagnosed as a sarcoma as a result of its rapid growth, cellularity, and
      sometimes prominent mitotic activity. A recurrent translocation t(17;22) has been
      identified in nodular fasciitis, fusing the coding region of USP6 to the promoter
      region of MYH9, and resulting in increased USP6 expression. A subset of cases
      show USP6 rearrangement without the typical fusion variants by RT-PCR, or any
      MYH9 rearrangement by FISH. We sought to further characterize such tumors using
      molecular diagnostic assays. A novel RT-PCR assay was designed to detect the two
      known MYH9-USP6 fusion types in formalin-fixed paraffin-embedded and frozen
      tissue, and a break-apart FISH assay was designed to detect USP6 rearrangement.
      Twenty-six cases of nodular fasciitis diagnosed between 2002 and 2013 were
      retrieved from the pathology files of our institutions and were confirmed to be
      positive by FISH and/or RT-PCR. Seven samples showed USP6 rearrangement by FISH
      but were negative for MYH9-USP6 fusion by RT-PCR; these cases were subjected to a
      next-generation sequencing assay utilizing anchored multiplex PCR technology.
      This assay targets a single partner gene associated with fusions in bone and soft
      tissue tumors for agnostic detection of gene fusion partners. Novel fusion
      partners were identified in all seven cases and confirmed by RT-PCR.
      Structurally, all fusions consisted of the juxtaposition of the entire coding
      region of USP6 with the promoter of the partner gene, driving increased USP6
      expression. This study confirms the neoplastic nature of nodular fasciitis,
      defines additional pathogenic fusion partners, and adds to the growing body of
      literature on USP6-associated neoplasia. Given the diagnostic challenges of these
      tumors, molecular assays can be useful ancillary tools; however, the prevalence
      of promoter swapping must be recognized when interpreting results.

PMID- 28752843
TI  - Loss of H3K27 trimethylation is not suitable for distinguishing malignant
      peripheral nerve sheath tumor from melanoma: a study of 387 cases including
      mimicking lesions.
AB  - The diagnosis of malignant peripheral nerve sheath tumor remains challenging,
      especially in the sporadic setting. Malignant peripheral nerve sheath tumor is a
      rare malignancy, and owing to the lack of specific histological criteria,
      immunohistochemical and molecular diagnostic markers, several differential
      diagnoses must be considered, in particular melanoma. Recently, inactivation of
      the polycomb repressive complex 2 (PRC2), induced by inactivating mutations in
      two of its critical constituents SUZ12 and EED, was reported in a large subset of
      malignant peripheral nerve sheath tumors. Homozygous PRC2 inactivation induces
      complete loss of trimethylation at lysine 27 of histone 3 (H3K27me3). Recent
      studies suggest that complete loss of H3K27me3 is highly specific for malignant
      peripheral nerve sheath tumor and may be a useful immunohistochemical diagnostic
      marker. Therefore, to determine the specificity of the complete loss of H3K27me3
      expression in the context of the differential diagnosis of malignant peripheral
      nerve sheath tumor from melanoma (its major potential mimic), we performed
      H3K27me3 immunohistochemistry in a pathologically and genetically well
      characterized cohort of primary (neurofibromatosis type 1 (NF1), radiation
      associated and sporadic context) malignant peripheral nerve sheath tumors (n=122)
      and in a cohort or primary (desmoplastic) and metastatic melanomas (n=265). In
      total, 88 (72%) malignant peripheral nerve sheath tumors, including 46 (71%) NF1
      associated, 4 (100%) radiation-associated, and 38 (72%) sporadic tumors, showed
      complete loss of H3K27me3. We observed increased loss of H3K27me3 with increasing
      histological grade. Interestingly, we found complete loss of H3K27me3 in 37%
      (n=98) of all melanomas, including 25% (n=9) of primary desmoplastic melanomas.
      Moreover, partial loss ('mosaic' pattern) was observed in 23 (19%) of all
      malignant peripheral nerve sheath tumors and in 136 (51%) of all melanomas.
      Complete loss of H3K27me3 detected by immunohistochemistry is not specific for
      malignant peripheral nerve sheath tumor and cannot be used safely when
      distinguishing malignant peripheral nerve sheath tumor from melanoma.

PMID- 28752844
TI  - Routine use of clinical exome-based next-generation sequencing for evaluation of
      patients with thrombotic microangiopathies.
AB  - Next-generation sequencing is increasingly used for clinical evaluation of
      patients presenting with thrombotic microangiopathies because it allows for
      simultaneous interrogation of multiple complement and coagulation pathway genes
      known to be associated with disease. However, the diagnostic yield is undefined
      in routine clinical practice. Historic studies relied on case-control cohorts,
      did not apply current guidelines for variant pathogenicity assessment, and used
      targeted gene enrichment combined with next-generation sequencing. A clinically
      enhanced exome, targeting ~54 Mb, was sequenced for 73 patients. Variant analysis
      and interpretation were performed on genes with biological relevance in
      thrombotic microangiopathy (C3,CD46, CFB, CFH, CFI, DGKE, and THBD). CFHR3-CFHR1
      deletion status was also assessed using multiplex ligation-dependent probe
      amplification. Variants were classified using American College of Medical
      Genetics and Genomics guidelines. We identified 5 unique novel and 14 unique rare
      variants in 25% (18/73) of patients, including a total of 5 pathogenic, 4 likely
      pathogenic, and 15 variants of uncertain clinical significance. Nine patients had
      homozygous deletions in CFHR3-CFHR1. The diagnostic yield, defined as the
      presence of a pathogenic variant, likely pathogenic variant or homozygous
      deletion of CFHR3-CFHR1, was 25% for all patients tested. Variants of uncertain
      clinical significance were identified in 21% (15/73) of patients.These results
      illustrate the expected diagnositic yield in the setting of thrombotic
      microangiopathies through the application of standardized variant interpretation,
      and highlight the utility of such an approach. Sequencing a clinically enhanced
      exome to enable targeted, disease-specific variant analysis is a viable approach.
      The moderate rate of variants of uncertain clinical significance highlights the
      paucity of data surrounding the variants in our cohort and illustrates the need
      for expanded variant curation resources to aid in thrombotic microangiopathy
      related disease variant classification.

PMID- 28752845
TI  - Mismatch repair status and PD-L1 expression in clear cell carcinomas of the ovary
      and endometrium.
AB  - Clear cell carcinoma represents a distinct histologic type of mullerian carcinoma
      that is resistant to conventional chemotherapy. Expression of programmed cell
      death ligand (PD-L1) has been associated with immune evasion in numerous tumor
      types and may be used to identify patients who will benefit from targeted
      immunotherapy, particularly in the setting of mismatch repair defects. We
      evaluated PD-L1 expression in 23 ovarian clear cell carcinomas and 21 endometrial
      clear cell carcinomas, and correlated expression with mismatch repair status.
      Tumor PD-L1 staining was seen in 43% of ovarian tumors and 76% of endometrial
      tumors, including 71% of cases (67% of ovarian and 75% of endometrial) with
      mismatch repair defects. Extensive tumoral staining (>50%) was seen in only one
      case (an endometrial case with MSH6 loss). However, tumoral PD-L1 expression
      remained common in mismatch repair-intact tumors and mismatch repair status was
      not significantly correlated with PD-L1 expression. The increased incidence of PD
      L1 positivity in tumor cells (P=0.04) in endometrial vs ovarian clear cell
      carcinomas suggests differences in the tumor microenvironment of these
      histologically and molecularly similar tumors that may inform treatment options.
      These results suggest that clear cell histology may be a useful susceptibility
      marker for immunotherapy targeting the PD-1/PD-L1 axis irrespective of mismatch
      repair status, particularly in endometrial carcinomas.

PMID- 28752847
TI  - Neuroendocrinology: Integrated stress response linked to TBI.

PMID- 28752846
TI  - The identification of challenges in tissue collection for biomarker studies: the
      Q-CROC-03 neoadjuvant breast cancer translational trial experience.
AB  - One of the major challenges in biomarker development is the collection of tumor
      tissue of adequate quality for analysis. A prospective clinical trial was
      initiated to collect tissues from triple negative breast cancers prior to and
      after neoadjuvant chemotherapy in order to study the mechanisms of
      chemoresistance. Sixty patients had pre-chemotherapy biopsies performed by either
      a surgeon or a radiologist, while those with residual tumor after chemotherapy
      had research-only biopsies and/or surgical samples collected in liquid nitrogen,
      RNA-later and formalin. We examined each core for tumor cellularity, stromal
      content, and necrosis after which, RNA and DNA extraction was performed. We found
      that biopsies collected with ultrasound guidance were more likely to contain
      tumor than those collected by the surgeon. Patient reluctance to undergo research
      only biopsies after chemotherapy was not a problem. Pre-chemotherapy tumor
      biopsies frequently did not contain any tumor cells (15%) or did not have >=50%
      tumor content (63%). Indeed, 50% of patients had at least 2 pre-chemotherapy core
      biopsies with <50% tumor content. After chemotherapy, 30% of biopsy or surgical
      samples in patients with incomplete response did not contain any tumor. Finally,
      RNA-later not only made histopathological assessment of tumor content difficult,
      but yielded less DNA than fresh snap frozen samples. We recommend that high
      quality tissue procurement can be best accomplished if at least three image
      guided core biopsies be obtained per sample, each of these cores be examined for
      tumor cellularity and that at least some of them be freshly snap frozen in liquid
      nitrogen.

PMID- 28752848
TI  - The skinny on obesity and cancer.
AB  - Obesity now rivals smoking as one of the leading preventable causes of cancer.
      Obesity-associated neutrophilia is now shown to enhance breast cancer metastasis
      and to be reversible through dietary modification and weight loss.

PMID- 28752849
TI  - Corrigendum: Pramel7 mediates ground-state pluripotency through proteasomal
      epigenetic combined pathways.
AB  - This corrects the article DOI: 10.1038/ncb3554.

PMID- 28752850
TI  - Journal metrics: what's in a number?

PMID- 28752851
TI  - A key HDAC6 dependency of ARID1A-mutated ovarian cancer.
AB  - Mutations in AT rich interactive domain 1A (ARID1A) are common in ovarian
      cancers. A study now shows that HDAC6 activity is required for survival of
      ovarian cancer cells bearing ARID1A mutations. HDAC6 inhibition selectively
      promotes apoptosis of ARID1A-inactivated cells, supporting the use of HDAC6
      inhibition in the treatment of clear cell ovarian cancer.

PMID- 28752852
TI  - Origin and regulation of a lung repair kit.
AB  - The lung undergoes a striking repair process in response to severe injuries such
      as influenza infection. A study now demonstrates that associated stem/progenitor
      cells are heterogeneous in nature and comprise subpopulations dominated by
      hypoxia/Notch or Wnt signalling. Modulation of this heterogeneity in favour of
      functional repair may have therapeutic value.

PMID- 28752853
TI  - Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced
      cytoplasmic translocation.
AB  - The Hippo pathway controls organ size and tissue homeostasis, with deregulation
      leading to cancer. The core Hippo components in mammals are composed of the
      upstream serine/threonine kinases Mst1/2, MAPK4Ks and Lats1/2. Inactivation of
      these upstream kinases leads to dephosphorylation, stabilization, nuclear
      translocation and thus activation of the major functional transducers of the
      Hippo pathway, YAP and its paralogue TAZ. YAP/TAZ are transcription co-activators
      that regulate gene expression primarily through interaction with the TEA domain
      DNA-binding family of transcription factors (TEAD). The current paradigm for
      regulation of this pathway centres on phosphorylation-dependent nucleocytoplasmic
      shuttling of YAP/TAZ through a complex network of upstream components. However,
      unlike other transcription factors, such as SMAD, NF-kappaB, NFAT and STAT, the
      regulation of TEAD nucleocytoplasmic shuttling has been largely overlooked. In
      the present study, we show that environmental stress promotes TEAD cytoplasmic
      translocation via p38 MAPK in a Hippo-independent manner. Importantly, stress
      induced TEAD inhibition predominates YAP-activating signals and selectively
      suppresses YAP-driven cancer cell growth. Our data reveal a mechanism governing
      TEAD nucleocytoplasmic shuttling and show that TEAD localization is a critical
      determinant of Hippo signalling output.

PMID- 28752854
TI  - CTCF fences make good neighbours.
AB  - CCCTC-binding factor (CTCF) sites are enriched at the boundaries of topologically
      associated domains (TADs), but their function within TADs is unclear. Removal of
      sub-TAD CTCF sites adjacent to the alpha-globin enhancers is now shown to result
      in inappropriate activation of neighbouring genes. Intra-TAD enhancer insulation
      might be broadly important for tissue specificity of enhancers.

PMID- 28752855
TI  - Corrigendum: Pulsatile cell-autonomous contractility drives compaction in the
      mouse embryo.
AB  - This corrects the article DOI: 10.1038/ncb3185.

PMID- 28752856
TI  - Multiple sclerosis: Treatment of cognitive impairment in secondary progressive
      MS.

PMID- 28752858
TI  - Neurodevelopmental disorders: Gene therapy for mucopolysaccharidosis shows
      promise.

PMID- 28752857
TI  - Insights into the mechanisms of deep brain stimulation.
AB  - Despite long-term and widespread use of deep brain stimulation (DBS) in a variety
      of neurological conditions, the underlying mechanisms of action have been
      elusive. Growing evidence suggests that DBS acts through multimodal mechanisms
      that are not limited to inhibition and excitation of basal ganglia circuits. DBS
      also seems to act over variable time spans - for example, the effects on tremor
      are immediate, whereas the effects on dystonia emerge over several weeks -
      suggesting that large networks are targeted. Studies reviewing the use of DBS in
      pain and obsessive-compulsive disorder have demonstrated direct involvement of
      axonal fibres rather than grey matter. In this Review, we draw on clinical and
      experimental data to examine the various hypotheses that have been put forward to
      explain the effects of DBS. In agreement with several other experts, we suggest
      that the term 'deep brain stimulation' warrants modification. A potentially more
      accurate term is 'deep brain neuromodulation', as the mode of action spans an
      array of therapeutic effects over a variable period of time, and is not just
      limited to 'stimulation' of the basal ganglia brain centres. Terms such as
      'electrical neuro-network modulation' may be useful for applications in which
      deep brain structures are not the primary target.

PMID- 28752859
TI  - MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in
      breast cancer.
AB  - MicroRNAs (miRNAs) have been proven to be involved in cell metastasis and
      angiogenesis by interaction with the target mRNAs. Evidence has been confirmed
      that miR-140-5p is a tumor suppressor in human cancers such as breast cancer.
      However, the potential molecular mechanism of miR-140-5p in breast cancer
      invasion and angiogenesis is still poorly understood. According to our study, we
      reported that miR-140-5p inhibited the tumor invasion and angiogenesis of breast
      cancer cells both in vitro and in vivo by targeting VEGF-A. The mRNA amount of
      miR-140-5p was decreased in the breast cancer clinical samples and breast cancer
      with metastasis compared with the corresponding adjacent normal tissues and
      cancer without metastasis. MiR-140-5p mimics and a negative control were
      transfected into human MCF-7 and MDA-MB-231 cells. Transwell chambers were used
      to detect the invasive ability of the cells, and the angiogenic ability was
      assessed by tube-formation assay. The markers of invasion and angiogenesis, VEGF
      A, CD31 and MMP-9, were detected by using immunohistochemistry and western blot
      analysis in vivo. VEGF-A was verified as a possible target gene of miR-140-5p,
      and corroborated by dual-luciferase reporter and ELISA. Taken together, the study
      elucidates the molecular mechanisms by which miR-140-5p inhibits breast cancer
      metastasis and angiogenesis, and provides a potent evidence for the development
      of a novel microRNA-targeting anticancer strategy for breast cancer patients.

PMID- 28752860
TI  - Enhancing the cytotoxicity of chemoradiation with radiation-guided delivery of
      anti-MGMT morpholino oligonucleotides in non-methylated solid tumors.
AB  - The DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) is
      epigenetically silenced in some tumors by MGMT gene promoter methylation. MGMT
      hypermethylated solid tumors have enhanced susceptibility to the cytotoxic
      effects of alkylating chemotherapy such as temozolomide, compared with non
      methylated tumors. In glioblastoma, subjects with MGMT hypermethylation have
      significantly longer survival rates after chemoradiotherapy. We report the first
      successful use of a non-ablative dose of ionizing radiation to prime human cancer
      cells to enhance the uptake of unmodified anti-MGMT morpholino oligonucleotide
      (AMON) sequences. We demonstrate >40% reduction in the in vitro proliferation
      index and cell viability in radiation-primed MGMT-expressing human solid tumor
      cells treated with a single dose of AMONs and temozolomide. We further
      demonstrate the feasibility of using a non-ablative dose of radiation in vivo to
      guide and enhance the delivery of intravenously administered AMONs to achieve 50%
      MGMT knockdown only at radiation-primed tumor sites in a subcutaneous tumor
      model. Local upregulation of physiological endocytosis after radiation may have a
      role in radiation-guided uptake of AMONs. This approach holds direct
      translational significance in glioblastoma and brain metastases where radiation
      is part of the standard of care; our approach to silence MGMT could overcome the
      significant problem of MGMT-mediated chemoresistance.

PMID- 28752861
TI  - Kruppel-like factor 4 acts as a potential therapeutic target of Sijunzi decoction
      for treatment of colorectal cancer.
AB  - Sijunzi decoction (SJZD) is a traditional Chinese medicine prescription for the
      prevention and treatment of colorectal cancer. Our study is aimed to identify the
      potential therapeutic target of SJZD. Microarray analysis was performed on the
      patients with colorectal cancer under treatment of SJZD. The mRNA targets of SJZD
      were predicted by BATMAN-TCM database and were further identified by integrated
      analysis of expression data from TCGA. The correlation of gene expression and
      clinical characteristics was analyzed. Microarray analysis indicated that Kruppel
      like factor 4 (KLF4) was significantly upregulated after intervention of SJZD.
      BATMAN-TCM prediction showed that KLF4 was an mRNA target of SJZD and it was
      downregulated in colorectal cancer by integrated analysis of expression data from
      TCGA. KLF4 may act as an administered indicator to assess whether adjuvant
      postoperative pharmaceutical therapy is needed for patients with colorectal
      cancer. Low KLF4 expression was significantly correlated with reductions of
      overall survival and recurrence rate. Our results suggested that KLF4 may be the
      potential therapeutic target of SJZD for the treatment of colorectal cancer.

PMID- 28752862
TI  - Findings of Research Misconduct.

PMID- 28752863
TI  - Findings of Research Misconduct.

PMID- 28752864
TI  - CO diffusion as a re-orientation mechanism in the NaY zeolite.
AB  - Our work is devoted to DFT calculations of the relative rotational and
      diffusional barriers for CO motions in zeolite NaY. The diffusion jump of CO
      adsorbed in NaY from NaII to Na'II has been confirmed as the favored way for CO
      re-coordination via either the C or the O atom to the Na cations instead of the
      CO rotation, hence explaining the mechanism which is responsible for the CO
      exchange between different positions and the changes in the intensities of the
      vibrational IR spectra. The fine structure of the vibrational C-O bands is
      explained by the different CO locations of adsorbed mono- and dicarbonyl species.
      The calculated activation energy of intra-cage CO diffusion from NaII-CO to Na'II
      OC matches the respective experimental barrier observed in the NaX zeolite.

PMID- 28752865
TI  - Infrared spectra and anharmonic coupling of proton-bound nitrogen dimers N2-H+
      N2, N2-D+-N2, and 15N2-H+-15N2 in solid para-hydrogen.
AB  - The proton-bound nitrogen dimer, N2-H+-N2, and its isotopologues were
      investigated by means of vibrational spectroscopy. These species were produced
      upon electron bombardment of mixtures of N2 (or 15N2) and para-hydrogen (p-H2) or
      normal-D2 (n-D2) during deposition at 3.2 K. Reduced-dimension anharmonic
      vibrational Schrodinger equations were constructed to account for the strong
      anharmonic effects in these protonated species. The fundamental lines of proton
      motions in N2-H+-N2 were observed at 715.0 (NH+N antisymmetric stretch, nu4),
      1129.6 (NH+N bend, nu6), and 2352.7 (antisymmetric NN/NN stretch, nu3) cm-1, in
      agreement with values of 763, 1144, and 2423 cm-1 predicted with anharmonic
      calculations using the discrete-variable representation (DVR) method at the
      CCSD/aug-cc-pVDZ level. The lines at 1030.2 and 1395.5 cm-1 were assigned to
      combination bands involving nnu2 + nu4 (n = 1 and 2) according to theoretical
      calculations; nu2 is the N2N2 stretching mode. For 15N2-H+-15N2 in solid p-H2,
      the corresponding major lines were observed at 710.0 (nu4), 1016.7 (nu2 + nu4),
      1124.3 (nu6), 1384.8 (2nu2 + nu4), and 2274.9 (nu3) cm-1. For N2-D+-N2 in solid n
      D2, the corresponding major lines were observed at 494.0 (nu4), 840.7 (nu2 +
      nu4), 825.5 (nu6), and 2356.2 (nu3) cm-1. In addition, two lines at 762.0 (weak)
      and 808.3 cm-1 were tentatively assigned to be some modes of N2-H+-N2 perturbed
      or activated by a third N2 near the proton.

PMID- 28752866
TI  - Alginate-based hydrogels functionalised at the nanoscale using layer-by-layer
      assembly for potential cartilage repair.
AB  - Injuries to articular cartilage are frequently difficult to repair, in part
      because of the poor regenerative capacity of this tissue. To date, no successful
      system for complete regeneration of the most challenging cartilage defects has
      been demonstrated. The aim of this work was to develop functionalised hydrogels
      at the nanoscale by Layer-by-Layer (LbL) assembly to promote cartilage healing.
      Hydrogels, based on sodium alginate (NaAlg) and gelatin (G), were prepared by an
      external gelation method consisting of CaCl2 diffusion and genipin addition for G
      crosslinking. Successively, hydrogels were coated with G to obtain a positive
      charge on the surface, then functionalised by LbL assembly to create 16
      nanolayers, based on poly(styrene sulfonate)/poly(allyl amine) (PSS/PAH),
      including a specific peptide sequence (CTATVHL) and transforming growth factors
      beta1 (TGF-beta1). Physico-chemical properties were evaluated by XPS, ATR-FTIR
      and rheological analyses while in vitro cytocompatibility was studied using
      bovine articular chondrocytes (BAC). XPS spectra showed N1s and S2p peaks,
      indicating that PAH and PSS have been introduced with success. ATR-FTIR indicated
      the specific PAH and PSS absorption peaks. Finally, the biomolecule incorporation
      influenced positively the processes of BAC adhesion and proliferation, and
      glycosamynoglycan secretion. The functionalised alginate-based hydrogels
      described here are ideally suited to chondral regeneration in terms of their
      integrity, stability, and cytocompatibility.

PMID- 28752867
TI  - Synthesis and evaluation of biological properties of ferrocenyl-podophyllotoxin
      conjugates.
AB  - Three types, esters, amides and 1,2,3-triazoles, of ferrocenyl-podophyllotoxin
      conjugates were synthesised, and their anticancer activity was evaluated. We
      observed that the most potent ferrocenyl derivatives were esters. Esters 15, 16
      and 17 acted in a similar way to podophyllotoxin, i.e. reduced the number of G1
      phase cells and induced G2/M blockage, while esters 14 and 18 and amide 19
      blocked cells in S phase in a similar manner to etoposide.

PMID- 28752868
TI  - A Waugh type [CoMo9O32]6- cluster with atomically dispersed CoIV originates from
      Anderson type [CoMo6O24]3- for photocatalytic oxygen molecule activation.
AB  - An atomically dispersed Waugh type [CoMo9O32]6- cluster is obtained, employing
      the most flexible structure unit Anderson type [Co(OH)6Mo6O18]3- as a precursor.
      The structure of the [CoMo9O32]6- cluster is identified by single crystal X-ray
      diffraction and also well characterized by FT-IR, ESI-MS, UV-Vis, EA, and TGA
      spectroscopy. Its 3D framework forms a quasi 2D material and possesses curved
      edge triangle shape nanopores with a diameter of 8.9 A. The CoIV and MoVI
      oxidation states and the related valence band and electronic state of Co are
      definitely confirmed by X-ray photoelectron spectroscopy (XPS), ultraviolet
      photoemission spectroscopy (UPS), and bond valence sum (BVS). The [CoMo9O32]6-
      cluster is a typical n-type inorganic semiconductor with a HOMO-LOMO gap of ca.
      1.67 eV and exhibits reversible two-electron redox properties, evidenced by UPS,
      cyclic voltammetric (CV), and Mott-Schottky plot analyses. Furthermore,
      [CoMo9O32]6- can effectively generate 1O2 under laser (365 and 532 nm) and
      sunlight irradiation, detected using a water-soluble DAB probe. Such an n-type
      multielectron reservoir semiconductor anionic [CoMo9O32]6- cluster with thermal
      and electrochemical stability as an effective photosensitizer serves as a
      promising material in solar energy scavenging.

PMID- 28752869
TI  - Synthetic ability of dinuclear mesocates containing 1,3
      bis(diazinecarboxamide)benzene bridging ligands to form complexes of increased
      nuclearity. Crystal structures, magnetic properties and theoretical studies.
AB  - Triple stranded Ni-metallacyclic complexes Na2.5[Ni2(bpcb)3].0.5OH.18.5H2O (1)
      and Na2[Ni2(bpzcb)3].16H2O (2), and double stranded Cu-metallacyclic complexes
      [Cu2(bpcb)2(H2O)2].8H2O (3) and [Cu2(bpzcb)2(H2O)2].4H2O (4) have been assembled
      from the tailored bisbidentate bridging ligands, 1,3-bis(pyrimidine-2
      carboxamide)benzene (H2bpcb) and 1,3-bis(pyrazine-2-carboxamide)benzene
      (H2bpzcb), and the corresponding nitrate salts of the metal ions. Following the
      "complex as ligand" strategy, 1 can be assembled with either Ni2+, Co2+ ions or
      the [Mn(acen)Cl] complex to afford unique, neutral, bent trinuclear molecules
      [MIINi(bpcb)3].xH2O (5 and 6) and the 2D honeycomb-like complex
      (PPh4){[Ni2(bpcb)3]2[Mn(acen)]3} (7), respectively. In these cases, the Ni2 units
      are linked to the corresponding metal ions through amidate oxygen atoms and the
      outward nitrogen atom of one of the pyrimidine rings of the bcpb ligand. The
      assembly of 2 with Ln3+ ions (Ln3+ = Tb, Gd) leads to one dimensional complexes
      of formula [{[Ni2(bpzcb)3]Tb(H2O)5}(CF3SO3).THF.5H2O]n (8) and
      [{[Ni2(bpzcb)3]Ln(H2O)4(NO3)}.2THF.nH2O]n (9 and 10) (Ln3+ = Gd and Tb), where
      the dinuclear Ni2 units are joined to two Ln3+ ions exclusively through amidate
      oxygen atoms of two different ligands. The analyses of the magnetic data indicate
      that 1-4 exhibit intradinuclear ferromagnetic interactions between the metal ions
      through a spin polarisation mechanism, as supported by DFT calculations.
      Trinuclear complexes 5 and 6 show predominant antiferromagnetic coupling, which
      is a result of an antiferromagnetic interaction between one of the Ni2+ ions of
      the Ni2 unit and the M2+ ion through the pyrimidine bridging fragment that is
      stronger than the polarised ferromagnetic interaction between the Ni2+ ions
      through the bpcb ligand in the dinuclear [Ni2(bpcb)3]2- moiety. Complex 7 shows a
      dominant antiferromagnetic interaction between the Ni2+ and Mn2+, whereas the
      Ni2Ln (Ln3+ = Gd, Tb) chain complexes present ferromagnetic interactions inside
      the Ni2 mesocate unit as well as between the Ni2+ ions of the Ni2 unit and the
      Ln3+ ions. The magnetic exchange interactions in these new materials have been
      experimentally analysed and supported by theoretical DFT studies.

PMID- 28752870
TI  - Endothelium-induced three-dimensional invasion of heterogeneous glioma initiating
      cells in a microfluidic coculture platform.
AB  - Glioblastoma (GBM) is a highly invasive primary brain tumor that displays
      cellular heterogeneity, which is composed of glioma initiating cells (GICs) and
      their differentiated progeny. GICs play an important role in driving aggressive
      invasion. In particular, the interaction between GICs and blood vessels is
      critical because blood vessels are known to serve as routes for the invasion of
      GICs. However, the effect of endothelial cells on the three-dimensional (3D)
      invasion process of GICs as well as the spatial relationship between GICs and
      their differentiated progeny remains unclear. Here, we utilized a microfluidic
      device to recapitulate the 3D brain tumor microenvironments constituted by human
      umbilical vein endothelial cells (HUVECs) and type I collagen. Using the device,
      we found that HUVECs promoted the 3D invasion of heterogeneous glioma cell
      populations into type I collagen gel. The invasion induced by HUVECs was
      predominantly preceded by cells positive for nestin, a neural stem cell marker.
      In contrast, cells positive for tubulin beta3 (TUBB3), a differentiated cell
      marker, rarely preceded invasion. In addition, HUVECs induced the upregulation of
      TUBB3 in GICs. Finally, we found that the genes associated with invasion, such as
      integrins alpha2 and beta3, were significantly upregulated in the presence of
      HUVECs. These results as well as the experimental approach provide valuable
      knowledge for the development of effective therapeutic strategies targeting the
      aggressive invasion of GBM.

PMID- 28752871
TI  - Understanding the mobilisation of metal pollution associated with historical
      mining in a carboniferous upland catchment.
AB  - Point and diffuse pollution from metal mining has led to severe environmental
      damage worldwide. Mine drainage is a significant problem for riverine ecosystems,
      it is commonly acidic (AMD), but neutral mine drainage (NMD) can also occur. A
      representative environment for studying metal pollution from NMD is provided by
      carboniferous catchments characterised by a circumneutral pH and high
      concentrations of carbonates, supporting the formation of secondary metal
      minerals as potential sinks of metals. The present study focuses on understanding
      the mobility of metal pollution associated with historical mining in a
      carboniferous upland catchment. In the uplands of the UK, river water, sediments
      and spoil wastes were collected over a period of fourteen months, samples were
      chemically analysed to identify the main metal sources and their relationships
      with geological and hydrological factors. Correlation tests and principal
      component analysis suggest that the underlying limestone bedrock controls pH and
      weathering reactions. Significant metal concentrations from mining activities
      were measured for zinc (4.3 mg l-1), and lead (0.3 mg l-1), attributed to
      processes such as oxidation of mined ores (e.g. sphalerite, galena) or
      dissolution of precipitated secondary metal-minerals (e.g. cerussite,
      smithsonite). Zinc and lead mobility indicated strong dependence on
      biogeochemistry and hydrological conditions (e.g. pH and flow) at specific
      locations in the catchment. Annual loads of zinc and lead (2.9 and 0.2 tonnes per
      year) demonstrate a significant source of both metals to downstream river
      reaches. Metal pollution results in a large area of catchment having a depleted
      chemical status with likely effects on the aquatic ecology. This study provides
      an improved understanding of geological and hydrological processes controlling
      water chemistry, which is critical to assessing metal sources and mobilization,
      especially in neutral mine drainage areas.

PMID- 28752872
TI  - A study of glycaemic effects following acute anthocyanin-rich blueberry
      supplementation in healthy young adults.
AB  - The postprandial response to ingested carbohydrate is recognised as a marker of
      metabolic health. Postprandial hyperglycaemia is observed in type 2 diabetes
      mellitus and is a significant risk factor for cardiovascular disease. Cognitive
      deficits are also associated with type 2 diabetes. Therefore interventions which
      moderate postprandial glucose profiles are desirable. Here we investigated the
      impact of anthocyanin-rich wild blueberries on postprandial glucose response.
      Seventeen healthy young adults consumed a range of doses of freeze-dried wild
      blueberry powder, in smoothie form, in both sugar-matched and no-added-sugar
      conditions. Plasma glucose was determined by a capillary sampling method at
      baseline and at regular intervals up to 2.5 hours postprandially. Blueberries
      were observed to significantly extend the postprandial glucose response beyond
      the period observed for a sugar-matched control, characteristic of a beneficial
      glycaemic response. Furthermore, blueberries were observed to reduce peak
      postprandial glucose levels, although statistical significance was not achieved.
      The findings suggest a tempering of the postprandial glucose response in the
      presence of anthocyanin-rich blueberry, and are discussed with reference to
      likely glucoregulatory mechanisms of action and their implications for cognitive
      and type 2 diabetes research.

PMID- 28752873
TI  - Dietary linoleic acid intake and blood inflammatory markers: a systematic review
      and meta-analysis of randomized controlled trials.
AB  - PURPOSE: The aim of the present study was to investigate the effect of increasing
      dietary linoleic acid (LA) intake on the blood concentrations of inflammatory
      markers including cytokines, acute phase reactants and adhesion molecules in
      adults. METHODS: We comprehensively searched PubMed, Embase and Cochrane Library
      for eligible studies. Overall, 30 randomized controlled studies involving 1377
      subjects were included for meta-analysis. RESULTS: No significant effect of
      higher LA intake was observed for cytokines: tumor necrosis factor (SMD: -0.01;
      95% CI: -0.19 to 0.17), interleukin-6 (SMD: 0.11, 95% CI: -0.07 to 0.29),
      adiponectin (SMD: 0.17, 95% CI: -0.17 to 0.50) and monocyte chemoattractant
      protein 1 (SMD: 0.14, 95% CI: -0.33 to 0.60). Pooled effect size from 16 studies
      showed that the C-reactive protein (CRP) concentration was not significantly
      affected by increasing LA intake (SMD = 0.09, 95% CI: -0.05 to 0.24). However,
      subgroup and meta-regression analysis suggested that in subjects with a more
      profound increase of dietary LA intake, LA might increase the blood CRP level.
      Other acute phase reactants including fibrinogen and plasminogen activator
      inhibitor-1 and adhesion molecules were not significantly changed when LA was
      increased in diet. No significant heterogeneity or publication bias was observed,
      although only a limited number of eligible studies were included for some
      markers. CONCLUSION: Our meta-analysis suggested that increasing dietary LA
      intake does not have a significant effect on the blood concentrations of
      inflammatory markers. However, the extent of change in dietary LA intake might
      affect the effect of LA supplementation on CRP.

PMID- 28752874
TI  - A high-capacity dual core-shell structured MWCNTs@S@PPy nanocomposite anode for
      advanced aqueous rechargeable lithium batteries.
AB  - Anode materials with high capacity for aqueous rechargeable lithium batteries
      (ARLBs) are very rarely reported. Here we found that a dual core-shell structured
      MWCNTs@S@PPy nanocomposite prepared by us shows excellent electrochemical
      performance. Its initial discharge capacity in a saturated LiAc aqueous
      electrolyte is very high, which is up to 481 mA h g-1 based on the weight of the
      composite and 879 mA h g-1 based on the sulfur content. It shows excellent rate
      capability. When nanotube LiMn2O4 is used as a cathode, the assembled ARLB can
      deliver an energy density of 110 Wh kg-1 based on two electrodes and show
      excellent cycling. These results show great promise for the practical application
      of ARLBs.

PMID- 28752876
TI  - Three-step synthesis of 2,5,7-trisubstituted indoles from N-acetyl-2,4,6
      trichloroaniline using Pd-catalyzed site-selective cross-coupling.
AB  - We report a facile three-step synthesis of 2,5,7-trisubstituted indoles from N
      acetyl-2,4,6-trichloroaniline, with the first step featuring
      Pd/dihydroxyterphenylphosphine (DHTP)-catalyzed ortho-selective Sonogashira
      coupling followed by cyclization to afford 2-substituted 5,7-dichloroindoles.
      Subsequent introduction of aryl or alkenyl groups at the C7 position was achieved
      by Pd/DHTP-catalyzed site-selective Kumada-Tamao-Corriu coupling, with further
      substitution of the chlorine at the C5 position (Suzuki-Miyaura coupling or
      Buchwald-Hartwig amination) affording 2,5,7-trisubstituted indoles.

PMID- 28752875
TI  - Multimode smartphone biosensing: the transmission, reflection, and intensity
      spectral (TRI)-analyzer.
AB  - We demonstrate a smartphone-integrated handheld detection instrument capable of
      utilizing the internal rear-facing camera as a high-resolution spectrometer for
      measuring the colorimetric absorption spectrum, fluorescence emission spectrum,
      and resonant reflection spectrum from a microfluidic cartridge inserted into the
      measurement light path. Under user selection, the instrument gathers light from
      either the white "flash" LED of the smartphone or an integrated green laser diode
      to direct illumination into a liquid test sample or onto a photonic crystal
      biosensor. Light emerging from each type of assay is gathered via optical fiber
      and passed through a diffraction grating placed directly over the smartphone
      camera to generate spectra from the assay when an image is collected. Each
      sensing modality is associated with a unique configuration of a microfluidic
      "stick" containing a linear array of liquid chambers that are swiped through the
      instrument while the smartphone captures video and the software automatically
      selects spectra representative of each compartment. The system is demonstrated
      for representative assays in the field of point-of-care (POC) maternal and infant
      health: an ELISA assay for the fetal fibronectin protein used as an indicator for
      pre-term birth and a fluorescent assay for phenylalanine as an indicator for
      phenylketonuria. In each case, the TRI-analyzer is capable of achieving limits of
      detection that are comparable to those obtained for the same assay measured with
      a conventional laboratory microplate reader, demonstrating the flexibility of the
      system to serve as a platform for rapid, simple translation of existing
      commercially available biosensing assays to a POC setting.

PMID- 28752877
TI  - Hydrogen storage in bimetallic Ti-Al sub-nanoclusters supported on graphene.
AB  - Recent studies suggest that graphene decorated with light metal atoms is a
      feasible alternative for the design of the next generation of hydrogen storage
      systems, that is, materials which require a gravimetric content of at least 7.5
      wt%, and an adsorption energy of 0.2-0.6 eV per H2. We present a first principles
      study of hydrogen adsorption in titanium, and bimetallic Ti5-xAlx (x = 1-3) and
      Ti7-xAlx (x = 1-4) clusters supported on graphene. Our results for Ti5, Ti4Al,
      Ti7, and Ti6Al show that doping titanium clusters with small amounts of aluminum
      does not influence the cluster stability on graphene, but that notably, it
      enhances its hydrogen gravimetric content up to 3.2-3.6 wt%. A further increment
      of the aluminum concentration was found to reduce the cluster stability and to
      favor hydrogen desorption, as shown by our calculations for supported Ti3Al2,
      Ti2Al3, TiAl4 and Ti5Al2. An analysis of atomic charges and density of states
      reveals the role of charge transfer and orbital interactions in the stability of
      hydride and dihydrogen complexes in the studied systems. Our results support the
      hypothesis that a controlled introduction of small metal clusters to graphene is
      a feasible way to enhance its hydrogen gravimetric content, and it opens up the
      possibility of investigating other binary TMx-Ay (TM = transition metal and A =
      main group) clusters supported on graphene as promising candidates for hydrogen
      storage.

PMID- 28752880
TI  - Stereoselective synthesis of the viridiofungin analogue NA808 from a chiral
      tetrahydrofuran-carboxylic acid.
AB  - The viridiofungin analogue NA808 was synthesized by the stereoselective Ireland
      Claisen rearrangement of dienylmethyl ester, regioselective bromolactonization of
      beta-divinylpropanoic acid and retro-bromolactonization.

PMID- 28752878
TI  - Nanofluidic crystals: nanofluidics in a close-packed nanoparticle array.
AB  - With various promising applications demonstrated, nanofluidics has been of broad
      research interest in the past decade. As nanofluidics matures from a proof of
      concept towards practical applications, it faces two major barriers: expensive
      nanofabrication and ultra-low throughput. To date, the only material that enables
      nanofabrication-free, high-throughput, yet precisely controllable nanofluidic
      systems is the close-packed nanoparticle array, i.e. nanofluidic crystals.
      Recently, significant progress in nanofluidics has been made using nanofluidic
      crystals, including high-current ionic diodes, high-power energy harvesters,
      efficient biomolecular separation, and facile biosensors. Nanofluidic crystals
      are seen as a key to applying nanofluidic concepts to real-world applications. In
      this review, we introduce the key concepts and models in nanofluidic crystals,
      summarize the fabrication methods, and discuss the various applications of
      nanofluidic crystals in depth, highlighting their advantages in terms of simple
      fabrication, low cost, flexibility, and high throughput. Finally, we provide our
      perspectives on the future of nanofluidic crystals and their potential impacts.

PMID- 28752881
TI  - Sequential dielectric phase transitions induced by the vibrations of water
      molecules in an organic-inorganic hybrid halide (N-(2-ammoniumethyl)piperazinium)
      CuCl5.2H2O.
AB  - Organic-inorganic hybrids represent a new type of material showing promising
      properties. In this report, sequential dielectric transitions have been studied
      in an organic-inorganic hybrid halide, (N-2-AP)CuCl5.2H2O (N-2-AP = N-(2
      ammoniumethyl)piperazinium) (1). The packing structure of 1 displays discrete
      [CuCl5]3- rectangular pyramids and N-2-AP cations, which are linked by two water
      molecules, forming infinite hydrogen bond networks with inorganic and organic
      components along the b-axis. Characterization studies containing differential
      scanning calorimetry (DSC) measurements, variable-temperature X-ray diffraction
      and dielectric measurements were performed to investigate the phase transitions
      in 1. The deuterated sample of 1 (named 2) also exhibits a similar behavior to
      that in 1, but shows different phase transition temperatures in dielectric
      transitions. The arresting deuterated effect strongly confirms that the phase
      transitions in 1 are attributable to the local vibrations of water molecules
      resulting from the variation of hydrogen-bonding interactions.

PMID- 28752882
TI  - Commensurate-incommensurate adsorption and diffusion in ordered crystalline
      microporous materials.
AB  - For homologous series of linear chain molecules, there could be either a match,
      or mismatch, between the characteristic periodicity of the host structure and the
      characteristic length of the guest molecules. The major objective of this article
      is to highlight the influence of commensurateness, or incommensurateness, on both
      the adsorption and diffusion characteristics. Published experimental data, backed
      by molecular simulation results, are used to highlight the attendant non
      monotonicity in adsorption strengths and diffusivities. We demonstrate the
      possibility of separating mixtures of n-alkanes, n-alcohols, and hydrocarbon
      isomers by appropriate and judicious choice of the dimensions, topology, and
      connectivity of the crystalline host material. Of particular practical interest
      are entropy-based separations that manifest at pore saturation conditions,
      relying on differences in the saturation capacities of the constituent species;
      the exploiting of such entropy effects is discussed with the aid of several
      examples.

PMID- 28752883
TI  - Highlights from Kaleidoscope: A Discussion Meeting in Chemistry, Goa, India, July
      2016.
AB  - "Kaleidoscope: A Discussion Meeting in Chemistry" is an annual gathering of young
      Indian investigators working in various fields of chemistry and allied areas. The
      meeting serves as a common ground to cross-pollinate new research ideas and come
      up with coherent approaches to solve long-standing and challenging problems
      within an informal setting. The third installment of the meeting was hosted
      within the serene confines of the International Center, Goa, India from July 14th
      17th 2016. In this report, we provide an overview of the topics covered and the
      ensuing discussions which took place during Kaleidoscope-2016 in order to
      highlight the scientific rigour of the meeting.

PMID- 28752884
TI  - One-pot synthesis of dendritic Pt3Ni nanoalloys as nonenzymatic electrochemical
      biosensors with high sensitivity and selectivity for dopamine detection.
AB  - Preparation of Pt-based nanocatalysts with high catalytic activity and
      exploration of their novel applications have attracted significant interest in
      the nanoscale field. Herein, we report a facile synthesis of dendritic Pt3Ni
      nanoalloys and their applications for electrochemical nonenzymatic dopamine
      biosensors. As a result of their unique structure, the dendritic Pt3Ni nanoalloys
      show high electrocatalytic activity towards dopamine oxidation. Amperometric
      dopamine biosensors based on dendritic Pt3Ni nanoalloy microelectrode exhibit a
      wide linear detection ranges from 0.5 MUM to 250 MUM with ultrahigh sensitivity,
      fast response, and excellent selectivity at a potential of 0.3 V in a 0.1 M
      phosphate buffered solution (pH = 7.2). The limit of detection on dendritic Pt3Ni
      nanoalloy microelectrodes can decrease down to 10 nM, which is the least
      concentration of dopamine in serum samples with a value of sensitivity up to 4.6
      MUA mg-1Pt cm-2. This study shows an effective approach for the development of
      dendritic Pt3Ni nanoalloys as electrocatalysts for electrochemical nonenzymatic
      dopamine biosensors.

PMID- 28752885
TI  - Effects of preparation on nutrient and environmental contaminant levels in Arctic
      beluga whale (Delphinapterus leucas) traditional foods.
AB  - For Canadian Arctic indigenous populations, marine mammal (MM) traditional foods
      (TFs) represent sources of both important nutrients and hazardous environmental
      contaminants. Food preparation is known to impact the nutrient and environmental
      contaminant content of processed items, yet the impacts of preparation on
      indigenous Arctic MM TFs remain poorly characterized. In order to determine how
      the various processes involved in preparing beluga blubber TFs affect their
      levels of nutrients and environmental contaminants, we collected blubber samples
      from 2 male beluga whales, aged 24 and 37 years, captured during the 2014 summer
      hunting season in Tuktoyaktuk, Northwest Territories, and processed them
      according to local TF preparation methods. We measured the levels of select
      nutrients [selenium (Se), polyunsaturated fatty acids (PUFAs)] and contaminants
      [organochlorine pesticides, perfluoroalkyl and polyfluoroalkyl substances
      (PFASs), polybrominated diphenyl ethers, polychlorinated biphenyls, polycyclic
      aromatic hydrocarbons (PAHs), mercury (Hg)] in raw and prepared (boiled, roasted,
      aged) beluga blubber TFs. The impacts of beluga blubber TF preparation methods on
      nutrient and environmental contaminant levels were inconsistent, as the majority
      of processes either did not appear to influence concentrations or affected the
      two belugas differently. However, roasting and ageing beluga blubber consistently
      impacted certain compounds: roasting blubber increased concentrations of
      hydrophilic substances (Se and certain PFASs) through solvent depletion and
      deposited PAHs from cookfire smoke. The solid-liquid phase separation involved in
      ageing blubber depleted hydrophilic elements (Se, Hg) and some ionogenic PFASs
      from the lipid-rich liquid oil phase, while PUFA levels appeared to increase, and
      hydrophobic persistent organic pollutants were retained. Ageing blubber adjacent
      to in-use smokehouses also resulted in considerable PAH deposition to processed
      samples. Our findings demonstrated that contaminant concentration differences
      were greater between the two sets of whale samples, based on age differences,
      than they were within each set of whale samples, due to variable preparation
      methods. When considering means to minimize human contaminant exposure while
      maximizing nutrient intake, consumption of aged liquid from younger male whales
      would be preferred, based on possible PUFA enhancement and selective depletion of
      hydrophilic environmental contaminants in this food item.

PMID- 28752886
TI  - Correction: Zwitterionic pyrrolidene-phosphonates: inhibitors of the glycoside
      hydrolase-like phosphorylase Streptomyces coelicolor GlgEI-V279S.
AB  - Correction for 'Zwitterionic pyrrolidene-phosphonates: inhibitors of the
      glycoside hydrolase-like phosphorylase Streptomyces coelicolor GlgEI-V279S' by
      Sri Kumar Veleti et al., Org. Biomol. Chem., 2017, 15, 3884-3891.

PMID- 28752887
TI  - Half-metallic properties of 3d transition metal atom-intercalated graphene@MS2 (M
      = W, Mo) hybrid structures.
AB  - The energetics and electronic and magnetic properties of G/MS2 hybrid structures
      embedded with 3d transition metal atoms, TM@(G/MS2) (G = graphene; M = W, Mo; TM
      = Sc-Ni), have been systematically studied using first-principles calculations.
      TM atoms were found to be covalently bound to two-sided graphene and MS2 layers
      with sizable binding energies of 4.35-7.13 eV. Interestingly, a variety of
      electronic and magnetic properties were identified for these TM@(G/MS2) systems.
      Except for TM = Ni, all other systems were ferromagnetic, due to exchange
      splitting of the TM 3d orbitals. In particular, four TM@(G/MoS2) systems (TM = V,
      Mn, Fe, Co) and three TM@(G/WS2) systems (TM = Mn, Fe, Co) were half-metals or
      quasi half-metals, while Ni@(G/MoS2) and Ni@(G/WS2) were semiconductors with
      bandgaps of 33 and 37 meV, respectively. Further quasi-particle scattering theory
      analysis demonstrated that the origin of semiconducting or half-metallic
      properties could be well understood from the variation in on-site energy by the
      transition metal dichalcogenide substrate or the different on-site scattering
      potential induced by TM atoms. Our findings propose an effective route for
      manipulating the electronic and magnetic properties of graphene@MS2
      heterostructures, allowing their potential application in modern spintronic and
      electronic devices.

PMID- 28752888
TI  - Patterned surface anchoring of nematic droplets at miscible liquid-liquid
      interfaces.
AB  - We report on the internal configurations of droplets of nematic liquid crystals
      (LCs; 10-50 MUm-in-diameter; comprised of 4-cyano-4'-pentylbiphenyl and 4-(3
      acryloyloxypropyloxy)benzoic acid 2-methyl-1,4-phenylene ester) sedimented from
      aqueous solutions of sodium dodecyl sulfate (SDS) onto interfaces formed with
      pure glycerol. We observed a family of internal LC droplet configurations and
      topological defects consistent with a remarkably abrupt transition from
      homeotropic (perpendicular) to tangential anchoring on the surface of the LC
      droplets in the interfacial environment. Calculations of the interdiffusion of
      water and glycerol at the aqueous-glycerol interface revealed the thickness of
      the diffuse interfacial region of the two miscible liquids to be small (0.2-0.5
      MUm) compared to the diameters of the LC droplets on the experimental time-scale
      (15-120 minutes), leading us to hypothesize that the patterned surface anchoring
      was induced by gradients in concentration of SDS and glycerol across the diameter
      of the LC droplets in the interfacial region. This hypothesis received additional
      support from experiments in which the time of sedimentation of the LC droplets
      onto the interface was systematically increased and the droplets were photo
      polymerized to preserve their configurations: the configurations of the LC
      droplets were consistent with a time-dependent decrease in the fraction of the
      surface area of each droplet exhibiting homeotropic anchoring. Specifically, LC
      droplets with <10% surface area with tangential anchoring exhibited a bulk point
      defect within the LC droplet, whereas droplets with >10% surface area with
      tangential anchoring exhibited a boojum defect within the tangential region and a
      disclination loop separated the regions with tangential and homeotropic
      anchoring. The topological charge of these LC droplet configurations was found to
      be consistent with the geometrical theorems of Poincare and Gauss and also well
      described by computer simulations performed by minimization of a Landau-de Gennes
      free energy. Additional experimental observations (e.g., formation of "Janus
      like" particles with one hemisphere exhibiting tangential anchoring and the other
      perpendicular anchoring) and simulations (e.g., a size-dependent set of LC
      droplet configurations with <10% surface area exhibiting tangential anchoring)
      support our general conclusion that placement of LC droplets into miscible liquid
      liquid interfacial environments with compositional gradients can lead to a rich
      set of LC droplet configurations with symmetries and optical characteristics that
      are not encountered in LC droplet systems in homogeneous, bulk environments. Our
      results also reveal that translocation of LC droplets across liquid-liquid
      interfaces can define new transition pathways that connect distinct
      configurations of LC droplets.

PMID- 28752889
TI  - Computationally guided discovery of a reactive, hydrophilic trans-5-oxocene
      dienophile for bioorthogonal labeling.
AB  - The use of organic chemistry principles and prediction techniques has enabled the
      development of new bioorthogonal reactions. As this "toolbox" expands to include
      new reaction manifolds and orthogonal reaction pairings, the continued
      development of existing reactions remains an important objective. This is
      particularly important in cellular imaging, where non-specific background
      fluorescence has been linked to the hydrophobicity of the bioorthogonal moiety.
      Here we report that trans-5-oxocene (oxoTCO) displays enhanced reactivity and
      hydrophilicity compared to trans-cyclooctene (TCO) in the tetrazine ligation
      reaction. Aided by ab initio calculations we show that the insertion of a single
      oxygen atom into the trans-cyclooctene (TCO) ring system is sufficient to impart
      aqueous solubility and also results in significant rate acceleration by
      increasing angle strain. We demonstrate the rapid and quantitative cycloaddition
      of oxoTCO using a water-soluble tetrazine derivative and a protein substrate
      containing a site-specific genetically encoded tetrazine moiety both in vitro and
      in vivo. We anticipate that oxoTCO will find use in studies where hydrophilicity
      and fast bioconjugation kinetics are paramount.

PMID- 28752890
TI  - Primary care in the prevention, treatment and control of cardiovascular disease
      in sub-Saharan Africa.
AB  - Cardiovascular disease (CVD) is the frontrunner in the disease spectrum of sub
      Saharan Africa, with stroke and ischaemic heart disease ranked seventh and 14th
      as leading causes of death, respectively, on this sub-continent. Unfortunately,
      this region is also grappling with many communicable, maternal, neonatal and
      nutritional disorders. Limited resources and the high cost of CVD treatment
      necessitate that primary prevention should have a high priority for CVD control
      in sub-Saharan Africa. One major challenge of such an approach is how to equip
      primary care to respond promptly and effectively to this burden. We present a
      practical approach on how primary care in sub-Saharan Africa could effectively
      address the prevention, treatment and control of CVD on the subcontinent. For
      effective prevention, control and treatment of CVD in sub-Saharan Africa, there
      should be strategic plans to equip primary care clinics with well-trained allied
      healthcare workers who are supervised by physicians.

PMID- 28752891
TI  - Inhibition of nuclear Wnt signalling: challenges of an elusive target for cancer
      therapy.
AB  - : The highly conserved Wnt signalling pathway plays an important role in
      embryonic development and disease pathogenesis, most notably cancer. The
      'canonical' or beta-catenin-dependent Wnt signal initiates at the cell plasma
      membrane with the binding of Wnt proteins to Frizzled:LRP5/LRP6 receptor
      complexes and is mediated by the translocation of the transcription co-activator
      protein, beta-catenin, into the nucleus. beta-Catenin then forms a complex with T
      cell factor (TCF)/lymphoid enhancer binding factor (LEF) transcription factors to
      regulate multiple gene programmes. These programmes play roles in cell
      proliferation, migration, vasculogenesis, survival and metabolism. Mutations in
      Wnt signalling pathway components lead to constitutively active Wnt signalling
      that drives aberrant expression of these programmes and development of cancer. It
      has been a longstanding and challenging goal to develop therapies that can
      interfere with the TCF/LEF-beta-catenin transcriptional complex. This review will
      focus on the (i) structural considerations for targeting the TCF/LEF-beta-catenin
      and co-regulatory complexes in the nucleus, (ii) current molecules that directly
      target TCF/LEF-beta-catenin activity and (iii) ideas for targeting newly
      discovered components of the TCF/LEF-beta-catenin complex and/or downstream gene
      programmes regulated by these complexes. LINKED ARTICLES: This article is part of
      a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To
      view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc.

PMID- 28752892
TI  - Patterns of concomitant allergic reactions in patients suggest cross
      sensitization between octylisothiazolinone and methylisothiazolinone.
AB  - BACKGROUND: Recent animal tests have indicated cross-reactivity between
      methylisothiazolinone (MI), octylisothiazolinone (OIT), and benzisothiazolinone
      (BIT). OBJECTIVES: To retrospectively analyse concomitant reactions to different
      isothiazolinones in patients in an occupational dermatology clinic during the
      ongoing MI contact allergy epidemic. METHODS: We searched patch test files
      (January 2012 to February 2017) for patients with allergic reactions to OIT, BIT,
      and MI, and analysed their patch test results, occupations, exposure, and
      diagnoses. RESULTS: We found 61 (9.4%) allergic reactions to MI, 19 (2.9%)
      reactions to OIT and 9 (1.4%) reactions to BIT in a total of 647 consecutively
      tested patients. Seventeen (89%) of the OIT-positive patients had concomitant
      reactions to MI, whereas only 3 (33%) BIT-positive patients had allergic
      reactions to MI. The MI reactions in OIT-positive patients were almost
      exclusively extreme reactions (+++). Exposure to OIT was identified in 26% of the
      OIT-positive patients, and 56% of the BIT-positive patients had been exposed to
      BIT. CONCLUSIONS: Allergic reactions to OIT were strongly associated with extreme
      reactions to MI, which suggests cross-sensitization. In contrast, BIT reactions
      were mostly independent.

PMID- 28752893
TI  - The radical-SAM enzyme Viperin catalyzes reductive addition of a 5'-deoxyadenosyl
      radical to UDP-glucose in vitro.
AB  - Viperin, a radical-S-adenosylmethionine (SAM) enzyme conserved from fungi to
      humans, can restrict replication of many viruses. Neither the molecular mechanism
      underlying the antiviral activity of Viperin, nor its exact physiological
      function, is understood: most importantly, no radical-SAM activity has been
      discovered for Viperin. Here, using electron paramagnetic resonance (EPR)
      spectroscopy, mass spectrometry, and NMR spectroscopy, we show that uridine
      diphosphate glucose (UDP-glucose) is a substrate of a fungal Viperin (58%
      pairwise identity with human Viperin at the amino acid level) in vitro.
      Structural homology modeling and docking experiments reveal a highly conserved
      binding pocket in which the position of UDP-glucose is consistent with our
      experimental data regarding catalytic addition of a 5'-deoxyadenosyl radical and
      a hydrogen atom to UDP-glucose.

PMID- 28752894
TI  - Headache in Idiopathic Intracranial Hypertension: Findings From the Idiopathic
      Intracranial Hypertension Treatment Trial.
AB  - OBJECTIVE: To characterize the phenotype, headache-related disability, medical co
      morbidities, use of symptomatic headache medications, and headache response to
      study interventions in the Idiopathic Intracranial Hypertension Treatment Trial
      (IIHTT). METHODS: Patients with untreated IIH and mild vision loss enrolled in
      the IIHTT and randomized to acetazolamide (ACZ) and weight loss or placebo (PLB)
      and weight loss had prospective assessment of headache disability using the
      Headache Impact Test-6 (HIT-6) questionnaire. Subjects with headache at the
      baseline visit were assigned a headache phenotype using the International
      Classification for Headache Disorders version 3 beta (ICHD-3b). Medication
      overuse was determined using the participants' reported medication use for the
      preceding month and ICHD-3b thresholds for diagnosing medication overuse
      headache. We investigated relationships between headache disability and various
      other clinical characteristics at baseline and at 6 months. RESULTS: Headache was
      present in 139 (84%) of the 165 enrollees at baseline. The most common headache
      phenotypes were migraine (52%), tension-type headache (22%), probable migraine
      (16%), and probable tension-type headache (4%). Fifty-one (37%) participants
      overused symptomatic medications at baseline, most frequently simple analgesics.
      A similar amount of improvement in the adjusted mean (+/- standard error) HIT-6
      score occurred in the ACZ (-9.56 +/- 1.05) and PLB groups (-9.11 +/- 1.14) at 6
      months (group difference -0.45, 95% CI -3.50 to 2.60, P = .77). Headache
      disability did not correlate with any of the studies, variables of interest,
      which included: the lumbar puncture opening pressure at baseline or at 6 months,
      body mass index, the amount of weight lost, papilledema grade, perimetric mean
      deviation, or the use of hormonal contraception. Headache disability was
      significantly associated with patient-reported quality of life in the physical,
      mental, and visual domains. CONCLUSIONS: Headache was common, of varied
      character, disabling, and associated with poorer quality of life in our cohort of
      patients with mild visual impairment. The lack of correlation between headache
      disability and cerebrospinal fluid (CSF) pressure at baseline and at the end of
      the randomized phase of the study implies that headache in IIH may be related to
      factors other than intracranial hypertension, and that specific headache
      treatment is needed in addition to therapies directed at lowering CSF pressure.

PMID- 28752895
TI  - Development of resurgent and persistent sodium currents in mesencephalic
      trigeminal neurons.
AB  - Sodium channels play multiple roles in the formation of neural membrane
      properties in mesencephalic trigeminal (Mes V) neurons and in other neural
      systems. Mes V neurons exhibit conditional robust high-frequency spike
      discharges. As previously reported, resurgent and persistent sodium currents
      (INaR and INaP , respectively) may carry small currents at subthreshold voltages
      that contribute to generation of spike firing. These currents play an important
      role in maintaining and allowing high-frequency spike discharge during a burst.
      In the present study, we investigated the developmental changes in tetrodotoxin
      sensitive INaR and INaP underlying high-frequency spike discharges in Mes V
      neurons. Whole-cell patch-clamp recordings showed that both current densities
      increased one and a half times from postnatal day (P) 0-6 neurons to P7-14
      neurons. Although these neurons do not exhibit subthreshold oscillations or burst
      discharges with high-frequency firing, INaR and INaP do exist in Mes V neurons at
      P0-6. When the spike frequency at rheobase was examined in firing Mes V neurons,
      the developmental change in firing frequency among P7-14 neurons was significant.
      INaR and INaP density at -40 mV also increased significantly among P7-14 neurons.
      The change to an increase in excitability in the P7-14 group could result from
      this quantitative change in INaP. In neurons older than P7 that exhibit
      repetitive firing, quantitative increases in INaR and INaP density may be major
      factors that facilitate and promote high-frequency firing as a function of age in
      Mes V neurons.

PMID- 28752896
TI  - Metabolic reprogramming by HIF-1 activation enhances survivability of human
      adipose-derived stem cells in ischaemic microenvironments.
AB  - OBJECTIVES: Poor cell survival severely limits the beneficial effect of adipose
      derived stem cell (ADSC)-based therapy for disease treatment and tissue
      regeneration, which might be caused by the attenuated level of hypoxia-inducible
      factor-1 (HIF-1) in these cells after having been cultured in 21% ambient oxygen
      in vitro for weeks. In this study, we explored the role of pre-incubation in
      dimethyloxalylglycine (DMOG, HIF-1 activator) in the survivability of human ADSCs
      in a simulated ischaemic microenvironment in vitro and in vivo. The underlying
      mechanism and angiogenesis were also studied. MATERIALS AND METHODS:
      Survivability of ADSCs was determined in a simulated ischaemic model in vitro and
      a nude mouse model in vivo. Cell metabolism and angiogenesis were investigated by
      tube formation assay, flow cytometry, fluorescence staining and real-time
      polymerase chain reaction (RT-PCR) after DMOG treatment. RESULTS: The results of
      the experimental groups showed significant enhancement of ADSC survivability in a
      simulated ischaemic microenvironment in vitro and transplanted model in vivo.
      Study of the underlying mechanisms suggested that the improved cell survival was
      regulated by HIF-1-induced metabolic reprogramming including decreased reactive
      oxygen species, increased intracellular pH, enhanced glucose uptake and increased
      glycogen synthesis. Tube formation assay revealed higher angiogenic ability in
      the DMOG-treated group than that in control group. CONCLUSIONS: The promotion of
      HIF-1 level in ADSCs induced by DMOG preconditioning suggests a potential
      strategy for improving the outcome of cell therapy due to increased survival and
      angiogenic ability.

PMID- 28752897
TI  - Mitigating the burden of neurological disease.

PMID- 28752898
TI  - Contact lenses to slow progression of myopia.
AB  - The prevalence of myopia has been steadily rising, with 28 per cent of the global
      population said to be affected in 2010 and to rise to affect nearly 50 per cent
      by 2050. Increasing levels of myopia increase the risk of vision impairment and
      in particular, high myopia is associated with the risk of serious and permanent
      visual disability due to associated sight-threatening complications. To stem the
      burden associated with higher levels of myopia, there are efforts to slow the
      progression of myopia, and several optical and pharmaceutical strategies have
      been found useful in slowing myopia to varying degrees. More recently, numerous
      multifocal soft contact lenses and extended depth of focus soft contact lenses
      (collectively referred to as myopia control contact lenses) were found effective
      in slowing myopia. As opposed to overnight orthokeratology, myopia control
      contact lenses are worn during the day and the hypotheses proposed to explain the
      efficacy of these lenses are generally based on the premise that the stimulus for
      eye growth is a defocused retinal image with hyperopic blur either centrally or
      peripherally. Although the individual power profiles of the lenses vary, the
      contact lens generally incorporates 'positive power' to reduce the hyperopic blur
      and/or impose myopic defocus or in the case of the extended depth of focus lens,
      has a power profile designed to optimise retinal image quality for points on or
      in front of the retina. The use of soft contact lenses as a platform for myopia
      control offers an exciting and effective avenue to manage myopia but there is a
      need for further research on issues such as the mechanism underlying control of
      myopia, improving efficacy with lenses, and understanding rebound on
      discontinuation. More significantly, although contact lenses are generally safe
      and improve quality of life in older children, one of the major challenges for
      improved uptake and acceptance of contact lenses centres on the perceived risk of
      complications with lens wear. This issue needs to be addressed.

PMID- 28752899
TI  - Purinergic receptor P2Y6 contributes to 1-methyl-4-phenylpyridinium-induced
      oxidative stress and cell death in neuronal SH-SY5Y cells.
AB  - Oxidative stress and neural degeneration have been shown to be involved in the
      pathogenesis of Parkinson's disease (PD). The P2Y6 purinergic receptor (P2Y6R)
      has been shown to participate in the activation of microglia and the production
      of pro-inflammatory factors induced by lipopolysaccharide to cause neuronal loss.
      However, the function of P2Y6R during oxidative stress in neurons is unclear. In
      the present study, 1-methyl-4-phenylpyridinium (MPP+ ) treatment increased the
      level of UDP/P2Y6R on neuronal SH-SY5Y cells. Importantly, pharmacological
      inhibition of P2Y6R or knockdown of P2Y6R using a siRNA exerted an increased
      protective effect by preventing MPP+ -induced increases in the levels of reactive
      oxygen species (ROS), superoxide anion, inducible nitric oxide synthase (iNOS),
      and malondialdehyde (MDA) and down-regulation of superoxide dismutase 1 (SOD1)
      expression. UDP, an agonist of P2Y6R, enhanced the effects of MPP+ , which was
      also inhibited by apyrase or MRS2578. Additionally, P2Y6R knockdown also
      significantly reversed both the loss of cell viability and the increase in the
      levels of phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2)
      and p38 (p-p38) caused by MPP+ stimulation. However, the inhibition of the ERK1/2
      and p38 kinase signaling pathways had no effect on P2Y6R expression. Taken
      together, these results support the hypothesis that P2Y6R expressed on neuronal
      SH-SY5Y cell is associated with the progression of oxidative stress and cell
      death induced by MPP+ , suggesting that P2Y6R may play an important role in the
      pathogenesis of PD.

PMID- 28752900
TI  - Aberrant astrocytic expression of chondroitin sulfate proteoglycan receptors in a
      rat model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease.
      Progressive and systemic loss of motor neurons with gliosis in the central
      nervous system (CNS) is a neuropathological hallmark of ALS. Chondroitin sulfate
      proteoglycans (CSPGs) are the major components of the extracellular matrix of the
      mammalian CNS, and they inhibit axonal regeneration physically by participating
      to form the glial scar. Recently, protein tyrosine phosphatase sigma (PTPsigma)
      and leukocyte common antigen-related protein were discovered as CSPG receptors
      that play roles in inhibiting regeneration. Here we examined the expression of
      CSPG receptors in transgenic female rats overexpressing an ALS-linked mutant
      cytosolic Cu/Zn superoxide dismutase gene (SOD1). In contrast to controls,
      multiple immunofluorescence analyses revealed aberrant expression of CSPG
      receptors dominantly in reactive astrocytes, while PTPsigma expression in neurons
      decreased in the spinal ventral horns of ALS transgenic rats. The aberrant and
      progressive astrocytic expression of CSPG receptors and reactive astrocytes
      themselves may be therapeutic targets for reconstructing a regeneration
      supportive microenvironment under neurodegenerative conditions such as ALS.

PMID- 28752901
TI  - Pegaspargase-induced hypertriglyceridemia.

PMID- 28752902
TI  - Nitrifier-induced denitrification is an important source of soil nitrous oxide
      and can be inhibited by a nitrification inhibitor 3,4-dimethylpyrazole phosphate.
AB  - Soil ecosystem represents the largest contributor to global nitrous oxide (N2 O)
      production, which is regulated by a wide variety of microbial communities in
      multiple biological pathways. A mechanistic understanding of these N2 O
      production biological pathways in complex soil environment is essential for
      improving model performance and developing innovative mitigation strategies.
      Here, combined approaches of the 15 N-18 O labelling technique, transcriptome
      analysis, and Illumina MiSeq sequencing were used to identify the relative
      contributions of four N2 O pathways including nitrification, nitrifier-induced
      denitrification (nitrifier denitrification and nitrification-coupled
      denitrification) and heterotrophic denitrification in six soils (alkaline vs.
      acid soils). In alkaline soils, nitrification and nitrifier-induced
      denitrification were the dominant pathways of N2 O production, and application of
      the nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) significantly
      reduced the N2 O production from these pathways; this is probably due to the
      observed reduction in the expression of the amoA gene in ammonia-oxidizing
      bacteria (AOB) in the DMPP-amended treatments. In acid soils, however,
      heterotrophic denitrification was the main source for N2 O production, and was
      not impacted by the application of DMPP. Our results provide robust evidence that
      the nitrification inhibitor DMPP can inhibit the N2 O production from nitrifier
      induced denitrification, a potential significant source of N2 O production in
      agricultural soils.

PMID- 28752903
TI  - Erythropoietin prevents the effect of chronic restraint stress on the number of
      hippocampal CA3c dendritic terminals-relation to expression of genes involved in
      synaptic plasticity, angiogenesis, inflammation, and oxidative stress in male
      rats.
AB  - Stress-induced allostatic load affects a variety of biological processes
      including synaptic plasticity, angiogenesis, oxidative stress, and inflammation
      in the brain, especially in the hippocampus. Erythropoietin (EPO) is a
      pleiotropic cytokine that has shown promising neuroprotective effects.
      Recombinant human EPO is currently highlighted as a new candidate treatment for
      cognitive impairment in neuropsychiatric disorders. Because EPO enhances synaptic
      plasticity, attenuates oxidative stress, and inhibits generation of
      proinflammatory cytokines, EPO may be able to modulate the effects of stress
      induced allostatic load at the molecular level. The aim of this study was
      therefore to investigate how EPO and repeated restraint stress, separately and
      combined, influence (i) behavior in the novelty-suppressed feeding test of
      depression/anxiety-related behavior; (ii) mRNA levels of genes encoding proteins
      involved in synaptic plasticity, angiogenesis, oxidative stress, and
      inflammation; and (iii) remodeling of the dendritic structure of the CA3c area of
      the hippocampus in male rats. As expected, chronic restraint stress lowered the
      number of CA3c apical dendritic terminals, and EPO treatment reversed this
      effect. Interestingly, these effects seemed to be mechanistically distinct, as
      stress and EPO had differential effects on gene expression. While chronic
      restraint stress lowered the expression of spinophilin, tumor necrosis factor
      alpha, and heat shock protein 72, EPO increased expression of hypoxia-inducible
      factor-2alpha and lowered the expression of vascular endothelial growth factor in
      hippocampus. These findings indicate that the effects of treatment with EPO
      follow different molecular pathways and do not directly counteract the effects of
      stress in the hippocampus.

PMID- 28752904
TI  - Social Rank and Rejection Sensitivity as Mediators of the Relationship between
      Insecure Attachment and Disordered Eating.
AB  - AIM: The current study assessed a new interpersonal model for eating disorders
      (EDs), in which interpersonal rejection sensitivity (RS), appearance-based RS and
      social rank were hypothesised to mediate the relationship between insecure
      attachment and disordered eating. METHOD: The sample comprised a clinical ED
      group (N = 122) and a control group (N = 622). Participants were asked to
      complete a number of self-report measures related to the variables of interest.
      RESULTS: Invariance testing indicated that the model was structurally non
      invariant (different across groups). For the ED group, appearance-based RS and
      social rank were significant mediators of the relationship between insecure
      attachment and disordered eating. For the controls, the relationship between
      insecure attachment and disordered eating was mediated through multiple pathways
      involving interpersonal RS, appearance-based RS and social rank. CONCLUSION:
      These findings may inform existing therapies such as interpersonal psychotherapy
      for EDs, by emphasising the role of sensitivity to rejection in the development
      and maintenance of disordered eating. Copyright (c) 2017 John Wiley & Sons, Ltd
      and Eating Disorders Association.

PMID- 28752905
TI  - The quality of life of patients developed delirium after coronary artery bypass
      grafting is determined by cognitive function after discharge: A cross-sectional
      study.
AB  - AIMS: Postoperative delirium (POD) and declined cognitive function were common in
      patients (especially elderly patients) who underwent coronary artery bypass
      grafting (CABG), which may affect quality of life (QoL). The aim of this study
      was to determine the relationships among age, POD, declined cognitive function,
      and QoL in patients who underwent CABG. METHODS: Consecutive patients who
      underwent first time elective CABG and assessed for POD using Confusion
      Assessment Method for intensive care unit for 5 postoperative days from November
      2013 to March 2015 were recruited. A cross-sectional study was conducted during
      April 2015 to assess their cognitive function and QoL, using the Telephone
      Interview for Cognitive Status Scale and Medical Outcomes Study 36-Item Short
      Form Health Survey. The relationships among age, POD, declined cognitive
      function, and QoL were tested using path analysis. RESULTS: Declined cognitive
      function was associated with poorer QoL. POD was associated with declined
      cognitive function but was not associated with poorer QoL. Ageing was not
      associated with QoL but was associated with POD and declined cognitive function.
      CONCLUSION: The QoL of patients developed delirium after CABG is determined by
      cognitive function after discharge. Necessary strategies should be implemented to
      prevent POD and declined cognitive function, especially in elderly patients.

PMID- 28752906
TI  - Reply to "mitigating the burden of neurological disease".

PMID- 28752907
TI  - Down regulation of protective genes is associated with cellular and antibody
      mediated rejection.
AB  - : Despite advances in immunosuppressive therapy, rejection still remains the main
      obstacle to a successful transplant. This study aims to explore the gene
      expression profile of the rejection process in order to decrease the number of
      unnecessary endomyocardial biopsies in stable patients. METHODS: A total of 300
      formalin-fixed and paraffin-embedded (FFPE) endomyocardial biopsies sampled from
      63 heart allograft recipients were included in this study. Acute cellular
      rejection (ACR) and antibody-mediated rejection (AMR) were diagnosed by
      histological analysis and immunohistochemical C4d staining, respectively.
      Analysis of gene expression was performed by quantitative real-time polymerase
      chain reaction. The samples were grouped according to the ISHLT rejection
      classification, aiming the statistical analysis. RESULTS: There was a significant
      decrease in the HMOX1, AIF1, and CCL2 transcript over the post-transplantation
      period in non-rejection group (P<.001). Furthermore, the ADIPOR1, ADIPOR2,
      BCL2L1, and VEGFA protective genes were significantly downregulated in the ACR
      group (P<.05). ADIPOR2, BCL2L1, IL6, and NOS2 genes were also significantly
      downregulated in the AMR group than in the non-rejection group (P<.05).
      CONCLUSION: The downregulations of the protective genes contribute to the
      allograft rejection, and the archived FFPE samples are useful for the gene
      expression analysis aiming the allograft rejection surveillance.

PMID- 28752908
TI  - A sensible approach to making sense of oxygen sensing.

PMID- 28752909
TI  - Light irradiation helps magnetotactic bacteria eliminate intracellular reactive
      oxygen species.
AB  - Magnetotactic bacteria (MTB) demonstrate photoresponse. However, little is known
      about the biological significance of this behaviour. Magnetosomes exhibit
      peroxidase-like activity and can scavenge reactive oxygen species (ROS).
      Magnetosomes extracted from the Magnetospirillum magneticum strain AMB-1 show
      enhanced peroxidase-like activity under illumination. The present study
      investigated the effects of light irradiation on nonmagnetic (without
      magnetosomes) and magnetic (with magnetosomes) AMB-1 cells. Results showed that
      light irradiation did not affect the growth of nonmagnetic and magnetic cells but
      significantly increased magnetosome synthesis and reduced intracellular ROS level
      in magnetic cells. Quantitative reverse transcription polymerase chain reaction
      (qRT-PCR) was performed to analyse the expression level of magnetosome formation
      associated genes (mamA, mms6, mms13 and mmsF) and stress-related genes (recA,
      oxyR, SOD, amb0664 and amb2684). Results showed that light irradiation
      upregulated the expression of mms6, mms13 and mmsF. Furthermore, light
      irradiation upregulated the expression of stress-related genes in nonmagnetic
      cells but downregulated them in magnetic cells. Additionally, magnetic cells
      exhibited stronger phototactic behaviour than nonmagnetic ones. These results
      suggested that light irradiation could heighten the ability of MTB to eliminate
      intracellular ROS and help them adapt to lighted environments. This phenomenon
      may be related to the enhanced peroxidase-like activity of magnetosomes under
      light irradiation.

PMID- 28752910
TI  - Antioxidants for female subfertility.
AB  - BACKGROUND: A couple may be considered to have fertility problems if they have
      been trying to conceive for over a year with no success. This may affect up to a
      quarter of all couples planning a child. It is estimated that for 40% to 50% of
      couples, subfertility may result from factors affecting women. Antioxidants are
      thought to reduce the oxidative stress brought on by these conditions. Currently,
      limited evidence suggests that antioxidants improve fertility, and trials have
      explored this area with varied results. This review assesses the evidence for the
      effectiveness of different antioxidants in female subfertility. OBJECTIVES: To
      determine whether supplementary oral antioxidants compared with placebo, no
      treatment/standard treatment or another antioxidant improve fertility outcomes
      for subfertile women. SEARCH METHODS: We searched the following databases (from
      their inception to September 2016) with no language or date restriction: Cochrane
      Gynaecology and Fertility Group (CGFG) specialised register, the Cochrane Central
      Register of Studies (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, CINAHL and AMED.
      We checked reference lists of appropriate studies and searched for ongoing trials
      in the clinical trials registers. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) that compared any type, dose or combination of oral
      antioxidant supplement with placebo, no treatment or treatment with another
      antioxidant, among women attending a reproductive clinic. We excluded trials
      comparing antioxidants with fertility drugs alone and trials that only included
      fertile women attending a fertility clinic because of male partner infertility.
      DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible
      studies, extracted the data and assessed the risk of bias of the included
      studies. The primary review outcome was live birth; secondary outcomes included
      clinical pregnancy rates and adverse events. We pooled studies using a fixed
      effect model, and calculated odds ratios (ORs) with 95% confidence intervals
      (CIs) for the dichotomous outcomes of live birth, clinical pregnancy and adverse
      events. We assessed the overall quality of the evidence by applying GRADE
      criteria. MAIN RESULTS: We included 50 trials involving 6510 women. Investigators
      compared oral antioxidants, including combinations of antioxidants, N-acetyl
      cysteine, melatonin, L-arginine, myo-inositol, D-chiro-inositol, carnitine,
      selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10,
      pentoxifylline and omega-3-polyunsaturated fatty acids versus placebo, no
      treatment/standard treatment or another antioxidant.Very low-quality evidence
      suggests that antioxidants may be associated with an increased live birth rate
      compared with placebo or no treatment/standard treatment (OR 2.13, 95% CI 1.45 to
      3.12, P > 0.001, 8 RCTs, 651 women, I2 = 47%). This suggests that among
      subfertile women with an expected live birth rate of 20%, the rate among women
      using antioxidants would be between 26% and 43%.Very low-quality evidence
      suggests that antioxidants may be associated with an increased clinical pregnancy
      rate compared with placebo or no treatment/standard treatment (OR 1.52, 95% CI
      1.31 to 1.76, P < 0.001, 26 RCTs, 4271 women, I2 = 66%). This suggests that among
      subfertile women with an expected clinical pregnancy rate of 22%, the rate among
      women using antioxidants would be between 27% and 33%. Heterogeneity was
      moderately high.There was insufficient evidence to determine whether there was a
      difference between the groups in rates of miscarriage (OR 0.79, 95% CI 0.58 to
      1.08, P = 0.14, 18 RCTs, 2834 women, I2 = 23%, very low quality evidence). This
      suggests that, among subfertile women with an expected miscarriage rate of 7%,
      use of antioxidants would be expected to result in a miscarriage rate of between
      4% and 7%. There was also insufficient evidence to determine whether there was a
      difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI
      0.73 to 1.38, P = 0.98, 8 RCTs, 2163 women, I2 = 4%, very low quality evidence).
      This suggests that among subfertile women with an expected multiple pregnancy
      rate of 8%, use of antioxidants would be expected to result in a multiple
      pregnancy rate between 6% and 11%. Likewise, there was insufficient evidence to
      determine whether there was a difference between the groups in rates of
      gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10, P = 0.47, 3 RCTs,
      343 women, I2 = 0%, very low quality evidence). This suggests that among
      subfertile women with an expected gastrointestinal disturbance rate of 2%, use of
      antioxidants would be expected to result in a rate between 1% and 11%. Overall
      adverse events were reported by 35 trials in the meta-analysis, but there was
      insufficient evidence to draw any conclusions.Only one trial reported on live
      birth, clinical pregnancy or adverse effects in the antioxidant versus
      antioxidant comparison, and no conclusions could be drawn.Very low-quality
      evidence suggests that pentoxifylline may be associated with an increased
      clinical pregnancy rate compared with placebo or no treatment (OR 2.07, 95% CI
      1.20 to 3.56, P = 0.009, 3 RCTs, 276 women, I2 = 0%). This suggests that among
      subfertile women with an expected clinical pregnancy rate of 25%, the rate among
      women using pentoxifylline would be between 28% and 53%.There was insufficient
      evidence to determine whether there was a difference between the groups in rates
      of miscarriage (OR 1.34, 95% CI 0.46 to 3.90, P = 0.58, 3 RCTs, 276 women, I2 =
      0%) or multiple pregnancy (OR 0.78, 95% CI 0.20 to 3.09, one RCT, 112 women, very
      low quality evidence). This suggests that among subfertile women with an expected
      miscarriage rate of 4%, the rate among women using pentoxifylline would be
      between 2% and 15%. For multiple pregnancy, the data suggest that among
      subfertile women with an expected multiple pregnancy rate of 9%, the rate among
      women using pentoxifylline would be between 2% and 23%.The overall quality of
      evidence was limited by serious risk of bias associated with poor reporting of
      methods, imprecision and inconsistency. AUTHORS' CONCLUSIONS: In this review,
      there was very low-quality evidence to show that taking an antioxidant may
      provide benefit for subfertile women, but insufficient evidence to draw any
      conclusions about adverse events. At this time, there is limited evidence in
      support of supplemental oral antioxidants for subfertile women.

PMID- 28752911
TI  - The Hawthorne effect in direct observation research with physicians and patients.
AB  - RATIONALE, AIMS, AND OBJECTIVES: This study examines the degree to which a
      "Hawthorne effect" alters outpatient-visit content. METHODS: Trained research
      nurses directly observed 4454 visits to 138 family physicians. Multiple data
      sources were used to examine the Hawthorne effect including differences in
      medical record documentation for observed visits and the prior visit by the same
      patient, time use during visits on the first versus the second observation day of
      each physician, and report by the patient, physician, and observer of the effect
      of observation. RESULTS: Visits on the first versus the second observation day
      were longer by an average of 1 minute (P < .001); there were time-use differences
      for 4 of 20 behaviour categories evaluated. No effect of the observer on the
      interaction was reported by 74% of patients and 55% of physicians. Most of those
      that reported an affect indicated it was slight. Patients with non-White race,
      lower-educational level, and poorer health were more likely to report being
      affected by the observer. CONCLUSIONS: In a study that was designed to minimize
      the Hawthorne effect, the presence of an observer had little effect on most
      patient-physician visits but appeared to at least slightly effect a subgroup of
      vulnerable patients.

PMID- 28752912
TI  - Functional analysis of the cyclophilin PpiB role in bacterial cell division.
AB  - Escherichia coli PpiB is a peptidyl-prolyl cis/trans isomerase (PPIase, EC:
      5.2.1.8) with chaperone activity. Here, we show that the DeltappiB deletion
      strain and the PpiB over-expression wild-type strain are both characterized by
      defects in cell division involving milder or severe cell filamentation,
      respectively. Using various PpiB mutants, we show that the PPIase activity of
      PpiB is necessary for the observed cell filamentation, whereas other structural
      features apart from the active site are also important for this phenotype. Early
      divisome components zipA and ftsZ showed decreased expression in DeltappiB cells,
      whereas the corresponding proteins partially suppressed the division phenotype of
      DeltappiB cells as well. Although PpiB itself has no obvious specific affinity
      for the septal ring as a GFP translational fusion showed a diffuse cytoplasmic
      localization, it interacts with FtsZ employing the C-terminal FtsZ domain,
      decreases its GTPase activity and when over-expressed shows an inhibitory effect
      on the proper FtsZ localization at future division sites. Furthermore, additional
      putative PpiB prey proteins are able to partially restore the DeltappiB phenotype
      indicating that PpiB is able to control bacterial cell division by probably
      modulating the function of various other proteins which are indirectly associated
      with the process.

PMID- 28752913
TI  - Prevalence of retinal vein occlusion in the Australian National Eye Health
      Survey.
AB  - IMPORTANCE: In Australia, knowledge of the epidemiology of retinal vein occlusion
      remains scarce because of a paucity of recent population-based data. The National
      Eye Health Survey (2015-2016) provides an up-to-date estimate of the prevalence
      of retinal vein occlusion in non-Indigenous and Indigenous Australian adults.
      BACKGROUND: To determine the prevalence and associations of retinal vein
      occlusion in a national sample of Indigenous and non-Indigenous Australian
      adults. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A total of
      3098 non-Indigenous Australians (aged 50-98 years) and 1738 Indigenous
      Australians (aged 40-92 years) living in 30 randomly selected sites, stratified
      by remoteness. METHODS: Retinal vein occlusions were graded from retinal
      photographs using standardized protocols and recorded as central retinal vein
      occlusion or branch retinal vein occlusion. MAIN OUTCOME MEASURE: Prevalence of
      retinal vein occlusion. RESULTS: In the non-Indigenous population, the sampling
      weight adjusted prevalence of any retinal vein occlusion was 0.96% (95%
      confidence interval: 0.59, 1.6), with branch retinal vein occlusion observed in
      0.72% (95% confidence interval: 0.41, 1.2) and central retinal vein occlusion in
      0.24% (95% confidence interval: 0.13, 0.47). Any retinal vein occlusion was found
      in 0.91% (95% confidence interval: 0.47, 1.7) of Indigenous Australians aged 40
      years and over, with branch retinal vein occlusion observed in 0.83% (95%
      confidence interval: 0.40, 1.7) and central retinal vein occlusion in 0.07% (95%
      confidence interval: 0.02, 0.32). Older age (odds ratio = 1.64 per 10 years, P =
      0.006) and the presence of self-reported diabetes (odds ratio = 3.24, P = 0.006)
      were associated with any retinal vein occlusion after multivariable adjustments.
      Retinal vein occlusion was attributed as the cause of monocular vision loss
      (<6/12) in seven (0.25%) non-Indigenous and six (0.36%) Indigenous participants.
      CONCLUSIONS AND RELEVANCE: These data suggest that retinal vein occlusion is
      relatively uncommon in the non-Indigenous Australians aged 50 years and over and
      Indigenous Australians aged 40 years and over. Similar to previous Australian and
      international reports, the prevalence of retinal vein occlusion rose sharply with
      age.

PMID- 28752914
TI  - Research in epidemic and emergency situations: A model for collaboration and
      expediting ethics review in two Caribbean countries.
AB  - Various forms of research are essential in emergency, disaster and disease
      outbreak situations, but challenges exist including the long length of time it
      takes to get research proposals approved. Consequently, it would be very
      advantageous to have an acceptable model for efficient coordination and
      communication between and among research ethics committees/IRBs and ministries of
      health, and templates for expediting (done with speed and efficiency) ethical
      review of research proposals in emergency and epidemic situations to be used
      across the Caribbean and in other low and middle income countries. This project
      involved a literature search and the interviewing of ministry of health
      officials, public health practitioners, and research ethics committee/IRB members
      in Jamaica and St. Lucia, to obtain suggestions for the best model for efficient
      coordination and communication between research ethics committees (RECs), and
      developed a template for expediting review of research protocols in epidemic and
      emergency conditions.

PMID- 28752915
TI  - Prokaryotic diversity and community composition in the Salar de Uyuni, a large
      scale, chaotropic salt flat.
AB  - Salar de Uyuni (SdU), with a geological history that reflects 50 000 years of
      climate change, is the largest hypersaline salt flat on Earth and is estimated to
      be the biggest lithium reservoir in the world. Its salinity reaches saturation
      levels for NaCl, a kosmotropic salt, and high concentrations of MgCL2 and LiCl,
      both salts considered important chaotrophic stressors. In addition, extreme
      temperatures, anoxic conditions, high UV irradiance, high albedo and extremely
      low concentrations of phosphorous, make SdU a unique natural extreme environment
      in which to contrast hypotheses about limiting factors of life diversification.
      Geophysical studies of brines from different sampling stations show that water
      activity is rather constant along SdU. Geochemical measurements show significant
      differences in magnesium concentration, ranging from 0.2 to 2M. This work
      analyses the prokaryotic diversity and community structure at four SdU sampling
      stations, selected according to their location and ionic composition. Prokaryotic
      communities were composed of both Archaea (with members of the classes
      Halobacteria, Thermoplasmata and Nanohaloarchaea, from the Euryarchaeota and
      Nanohaloarcheota phyla respectively) and Bacteria (mainly belonging to
      Bacteroidetes and Proteobacteria phyla). The important differences in composition
      of microbial communities inversely correlate with Mg2+ concentration, suggesting
      that prokaryotic diversity at SdU is chaotropic dependent.

PMID- 28752916
TI  - Discovery and genomic analyses of hybridization between divergent lineages of
      Trypanosoma congolense, causative agent of Animal African Trypanosomiasis.
AB  - Hybrid populations and introgressive hybridization remain poorly documented in
      pathogenic micro-organisms, as such that genetic exchange has been argued to play
      a minor role in their evolution. Recent work demonstrated the existence of hybrid
      microsatellite profiles in Trypanosoma congolense, a parasitic protozoan with
      detrimental effects on livestock productivity in sub-Saharan Africa. Here, we
      present the first population genomic study of T. congolense, revealing a
      remarkable number of single nucleotide polymorphisms (SNPs), small
      insertions/deletions (indels) and gene deletions among 56 parasite genomes from
      ten African countries. One group of parasites from Zambia was particularly
      diverse, displaying a substantial number of heterozygous SNP and indel sites
      compared to T. congolense parasites from the nine other sub-Saharan countries.
      Genomewide 5-kb phylogenetic analyses based on phased SNP data revealed that
      these parasites were the product of hybridization between phylogenetically
      distinct T. congolense lineages. Other parasites within the same region in Zambia
      presented a mosaic of haplotypic ancestry and genetic variability, indicating
      that hybrid parasites persisted and recombined beyond the initial hybridization
      event. Our observations challenge traditional views of trypanosome population
      biology and encourage future research on the role of hybridization in spreading
      genes for drug resistance, pathogenicity and virulence.

PMID- 28752917
TI  - Pediatric Migraine Disability Assessment (PedMIDAS): Translation Into Brazilian
      Portuguese and Cross-Cultural Adaptation.
AB  - OBJECTIVE: To translate, perform the cross-cultural adaptation, and an initial
      validation of the Brazilian Portuguese version of PedMIDAS (BP-PedMIDAS).
      BACKGROUND: Pediatric Migraine Disability Assessment (PedMIDAS) was developed to
      measure the impact of migraine among children and adolescents. METHODS: PedMIDAS
      was subjected to translation, back-translation, and application of the
      questionnaire to 40 children and adolescents with migraine for confirmation
      validation. Once validated, the psychometric properties were tested through
      administration to 100 children and adolescents with migraine. RESULTS: The mean
      time required to complete BP-PedMIDAS was 135 +/- 51 seconds. BP-PedMIDAS had a
      Cronbach's coefficient alpha of 0.84 and a good stability (test-retest), with a
      good intraobserver and interobserver agreement (Pearson's correlation > 0.80) and
      correlated with the frequency of the headaches. These results mirrored those seen
      with PedMIDAS, further validating the interchangeability of the versions.
      CONCLUSION: BP-PedMIDAS has been shown to be useful for assessing disability in
      children and adolescents.

PMID- 28752918
TI  - Impact of HBV and S. mansoni on portal pressure: Synergy or innocent bystanders?

PMID- 28752919
TI  - Acute physiological and perceptual responses to high-load resistance exercise in
      hypoxia.
AB  - This study assessed whether hypoxia during high-load resistance exercise could
      enhance the acute physiological responses related to muscular development. Twelve
      trained men performed exercise in three conditions: normoxia (fraction of
      inspired oxygen [FI O2 ] = 21%), moderate-level hypoxia (FI O2  = 16%) and high
      level hypoxia (FI O2  = 13%). Exercise comprised high-load squats and deadlifts
      (5 * 5 using 80% of 1-repetition maximum with 180-s rest). Muscle oxygenation and
      activation were monitored during exercise. Metabolic stress was estimated via
      capillary blood sampling. Perceived fatigue and soreness were also quantified
      following exercise. While the hypoxic conditions appeared to affect muscle
      oxygenation, significant differences between conditions were only noted for
      maximal deoxyhaemoglobin in the deadlift (P = 0.009). Blood lactate concentration
      increased from 1.1 to 1.2 mmol l-1 at baseline to 9.5-9.8 mmol l-1 after squats
      and 10.4-10.5 mmol l-1 after deadlifts (P<=0.001), although there were no between
      condition differences. Perceived fatigue and muscle soreness were significantly
      elevated immediately and at 24 h following exercise, respectively, by similar
      magnitudes in all conditions (P<=0.001). Muscle activation did not differ between
      conditions. While metabolic stress is thought to moderate muscle activation and
      subsequent muscular development during hypoxic resistance training, it is not
      augmented during traditional high-load exercise. This may be explained by the low
      number of repetitions performed and the long interset rest periods employed
      during this training. These findings suggest that high-load resistance training
      might not benefit from additional hypoxia as has been shown for low- and moderate
      load training.

PMID- 28752920
TI  - Outcome of liver transplantation in patients with prior bariatric surgery.
AB  - Nonalcoholic fatty liver disease is becoming the leading cause of disease
      resulting in liver transplantation (LT). As a result of this trend, more LT
      candidates are presenting with prior history of bariatric surgery (BS). Over the
      last decade, 960 patients underwent LT at our institution; 11 (1.1%) had prior
      BS. The most common type of BS was Roux-en-Y gastric bypass (n = 9) with 1 sleeve
      gastrectomy and 1 jejunoileal bypass. A total of 9 patients underwent LT alone,
      and 2 underwent simultaneous liver-kidney transplantation. The most common
      indication for LT was nonalcoholic steatohepatitis (n = 10) with 5 having
      additional diagnosis of alcoholic liver disease. The 30-day reoperation rate was
      36.4% (n = 4); indications were bile duct repair (n = 3) and wound repair (n =
      1). In the first 6 months after LT, biliary complications were seen in 54.5% (n =
      6) of the patients. Both patient and graft survival rates at 1 and 2 years were
      81.8% (n = 9) and 72.7% (n = 8), respectively. A total of 8 patients (72.7%) had
      indications for liver biopsy after LT; significant macrovesicular steatosis was
      found in 2 (18.2%). In patients with a history of alcohol consumption, 2 (40.0%)
      relapsed after LT. Two patients (18.2%) had a history of diet-controlled diabetes
      before LT; 1 of these patients became insulin dependent after LT. Mean body mass
      index (BMI) at LT was 31.0 +/- 5.7 kg/m2 . Mean BMI at 1, 6, and 12 months after
      LT was 28.3 +/- 5.8, 28.0 +/- 3.2, and 31.0 +/- 6.6 kg/m2 , respectively. Mean
      preoperative albumin was 2.6 +/- 0.6 mg/dL. Patients showed improvement in
      albumin after LT, with mean albumin of 2.7 +/- 0.6 and 3.2 +/- 0.5 mg/dL at 1 and
      3 months, respectively. The liver profile was stable after LT, with mean
      aspartate aminotransferase of 32.9 +/- 18.4 and 26.6 +/- 19.8 IU/L and alanine
      aminotransferase of 28.0 +/- 17.5 and 30.2 +/- 17.0 IU/L at 6 and 12 months,
      respectively. In conclusion, outcomes of LT patients with prior BS are comparable
      with other transplant recipients with regards to patient and graft survival and
      post-LT complication rates. Liver Transplantation 23 1415-1421 2017 AASLD.

PMID- 28752921
TI  - Data-Driven Improvement in Prekindergarten Classrooms: Report From a Partnership
      in an Urban District.
AB  - In 2014-2015 and 2015-2016, a metropolitan school system in the southern United
      States embarked on a unique mission to improve the quality of its public
      prekindergarten programs through a partnership with a group of developmental
      researchers in an iterative, data-based venture. Data on 407 children in Year 1
      and 433 in Year 2 (who were enrolled in 26 classrooms and extensively observed)
      are presented from the first 2 years of the ongoing partnership. All children
      were 4 years of age. Variability in classroom practices, measured empirically,
      and variability in child outcomes provided the means to examine the relations
      between children's gains in academic and social-emotional areas and major areas
      of classroom practices. Lessons learned, the eight identified significant
      practices, implications, and next steps in the partnership are addressed.

PMID- 28752922
TI  - Molecular and functional analysis of the mce4 operon in Mycobacterium smegmatis.
AB  - Mycobacterium smegmatis contains 6 homologous mce (mammalian cell entry) operons
      which have been proposed to encode ABC-like import systems. The mce operons
      encode up to 10 different proteins of unknown function that are not present in
      conventional ABC transporters. We have analysed the consequences of individually
      deleting each of the genes of the mce4 operon of M. smegmatis, which mediates the
      transport of cholesterol. None of the mce4 mutants were able to grow in
      cholesterol suggesting that all these genes are required for its uptake and that
      none of them can be replaced by the homologous genes of the other mce operons.
      This result suggests that different mce operons do not provide redundant
      capabilities and that M. smegmatis, in contrast with Mycobacterium tuberculosis,
      is not able to use alternative systems to import cholesterol in the analysed
      culture conditions. Either deletion of the entire mce4 operon or single point
      mutations that eliminate the transport function cause a phenotype similar to the
      one observed in a mutant lacking all 6 mce operons suggesting a pleiotropic role
      for this system.

PMID- 28752923
TI  - LP-211, a selective 5-HT7 receptor agonist, increases novelty-preference and
      promotes risk-prone behavior in rats.
AB  - Gambling disorder is associated to an increased impulsivity, a high level of
      novelty-seeking and a dysregulation of the forebrain neurotransmission systems.
      However, the neurobiological mechanisms of this addictive disorder are not fully
      understood and no valid pharmacological approach has yet been approved. The
      present study aimed to investigate the effect of 5-HT7 receptor (5-HT7 R)
      stimulation with a brain penetrant and selective agonist, LP-211 (0.25 and 0.50
      mg kg-1 i.p.) during post-experience consolidation, (i) acutely in a novelty
      preference test (Exp. 1) or (ii) sub-chronically in the Probabilistic-Delivery
      Task (rPDT, commonly used to measure individual differences in risk proneness of
      rats; Exp. 2). Results of Exp. 1 showed that 5-HT7 R activation improves
      consolidation of chamber-shape memory in the novelty-preference test, leading to
      significant novelty-induced hyperactivity and recognition, in conditions where
      controls displayed a null-preference. These results suggest that 5-HT7 Rs may be
      involved in the consolidation of information inherent to spatial environments,
      facilitating the recognition of novelty. Furthermore, in the operant rPDT (Exp.
      2), 5-HT7 R activation shifts the choice towards a larger yet unlikely reward and
      turns the propensity of rats towards risk-prone behavior. Thus, 5-HT7 Rs
      stimulation apparently strengthens the consideration of future, bigger rewards,
      also enhancing the seeking of it by operant pokes. These effects may well be
      explained by LP-211 actions on hippocampal versus prefrontal cortex-mediated
      regulations, leading to improved (though suboptimal) strategy formation. However,
      further experiments are necessary to determine more in depth the serotonergic
      pathways involved.

PMID- 28752924
TI  - Couple Therapy with Veterans: Early Improvements and Predictors of Early Dropout.
AB  - Family services within Veterans Affairs Medical Centers fulfill an important role
      in addressing relationship distress among Veterans, which is highly prevalent and
      comorbid with psychopathology. However, even for evidence-based couple therapies,
      effectiveness is weaker compared to controlled studies, maybe because many
      Veteran couples drop out early and do not reach the "active" treatment stage
      after the 3-4 session assessment. In order to improve outcomes, it is critical to
      identify couples at high risk for early dropout, and understand whether couples
      may benefit from the assessment as an intervention. The current study examined
      (a) demographics, treatment delivery mode, relationship satisfaction, and
      psychological symptoms as predictors of dropout during and immediately following
      the assessment phase, and (b) changes in relationship satisfaction during
      assessment. 174 couples completed questionnaires during routine intake
      procedures. The main analyses focused on 140 male Veterans and their female
      civilian partners; 36.43% dropped out during the assessment phase and 24.74% of
      the remaining couples immediately following the first treatment session. More
      severe depressive symptoms in non-Veteran partners were associated with dropout
      during assessment. Relationship satisfaction improved significantly during the
      assessment phase for couples who did not drop out, with larger gains for non
      Veteran partners. No demographics or treatment delivery mode were associated with
      dropout. Although more research is needed on engaging couples at risk for early
      dropout and maximizing early benefits, the findings suggest that clinicians
      should attend to the civilian partner's and Veteran's depressive symptoms at
      intake and consider the assessment part of active treatment.

PMID- 28752925
TI  - Management of portal hypertension before and after liver transplantation.
AB  - Orthotopic liver transplantation (OLT) represents a curative treatment option for
      end-stage liver disease (ESLD). Although epidemiology of ESLD has recently
      changed due to the rising prevalence of nonalcoholic fatty liver disease and the
      decreased burden of hepatitis C virus infections due to highly effective
      antiviral regimens, the management of portal hypertension (PHT) remains a
      clinical challenge in the pre- and post-OLT setting. The measurement of the
      hepatic venous pressure gradient represents the most reliable but invasive tool
      for assessment of the severity of PHT. Although novel liver ultrasound and
      magnetic resonance-based elastography methods have been developed, their value to
      screen for liver fibrosis and PHT in transplanted patients remains to be
      established. Nonselective beta-blockers represent the cornerstone of medical
      treatment of PHT, but more studies on their effects on clinical endpoints after
      OLT are needed. Statins are widely used to treat hyperlipidemia, which is a
      common condition after OLT. Although a growing body of evidence suggests that
      statins decrease portal pressure and PHT-related complications in ESLD, studies
      on potential benefits of statins after OLT are lacking. Finally, transjugular
      intrahepatic portosystemic shunts (TIPS) are effective in decreasing PHT and seem
      to decrease mortality on the OLT waiting list. Moreover, TIPS does not have an
      impact on liver function nor complicate the transplant surgical procedures. TIPS
      may also be used after OLT, but the evidence is limited. In conclusion, whereas
      the management of PHT in patients with ESLD is based on strong evidence, further
      data on the value of noninvasive monitoring tools as well as on medical and
      invasive treatment options in the post-OLT setting are needed to improve
      management strategies in patients with recurrent PHT after liver transplantation.
      Liver Transplantation 24 112-121 2018 AASLD.

PMID- 28752926
TI  - Prognostic nutritional index predicts initial response to treatment and prognosis
      in metastatic castration-resistant prostate cancer patients treated with
      abiraterone.
AB  - OBJECTIVE: To determine if prognostic nutritional index (PNI) and its variation
      could predict initial response to treatment and prognosis in metastatic
      castration-resistant prostate cancer (mCRPC) patients treated with Abiraterone
      (AA). PATIENTS AND METHODS: One-hundred-twelve chemotherapy pretreated or
      chemotherapy-naive patients were scheduled for systemic treatment with AA. PNI
      levels were measured before and after one month of AA treatment. Univariate and
      multivariate logistic regression analyses were used to identify predictive
      factors of initial response to AA treatment. Univariable and Multivariable Cox
      regression analyses were performed to determine prognostic factors that were
      associated with PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS)
      and overall survival (OS). The Harrell concordance index with variables only or
      combined PNI data were used to evaluate the prognostic accuracy. RESULTS: Eighty
      one (72.3%) of 112 patients showed initial response to AA treatment, in which 15
      experienced PSA flare during AA treatment. In multivariate logistic regression
      analyses, high baseline PNI level, PSA level decrease during the first month of
      AA treatment and PNI level elevation during the first month of AA treatment were
      significantly correlated with initial response to AA treatment. In multivariate
      Cox regression analysis, low PNI level remained significant predictors of OS,
      rPFS and PSA-PFS. The estimated c-index of the multivariate model for OS
      increased from 0.82 without PNI to 0.83 when PNI added. CONCLUSION: Independent
      of PSA level variation, PNI level elevation during the first month of AA
      treatment and high baseline PNI level were significantly correlated with initial
      response to AA treatment. In addition, low pretreatment PNI level is a negative
      independent prognosticator of survival outcomes in mCRPC treated with AA and also
      increases the accuracy of established prognostic model.

PMID- 28752927
TI  - Beta-blockers in patients with advanced liver disease: Has the dust settled?

PMID- 28752928
TI  - Retrospective evaluation of and risk factor analysis for presumed fluid overload
      in cats with urethral obstruction: 11 cases (2002-2012).
AB  - OBJECTIVE: To describe patient characteristics, treatment, and outcome in male
      cats with urethral obstruction (UO) and fluid overload (FO), and to determine
      risk factors for the development of FO. DESIGN: Retrospective case-control study
      from 2002-2012. ANIMALS: Eleven client-owned cats with UO that developed
      respiratory distress secondary to suspected FO and 51 control cats with UO
      without FO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records
      of cats with UO and FO were identified. FO was defined as the development of
      respiratory distress secondary to pleural effusion or pulmonary edema while
      receiving IV fluids. To identify risk factors for FO, variables for cats that
      developed FO were compared with variables from a randomly selected control group
      of unaffected UO cats during the same time period. Variables analyzed included
      patient signalment, previous medical history, serum biochemical data, respiratory
      rate, cardiac auscultation abnormalities, admission systolic blood pressure,
      intravenous fluid administration, thoracic imaging, treatment, duration and cost
      of hospitalization, and outcome. Echocardiogram identified heart disease in 5/6
      cats with FO. Cost (2.9 times as much) and median duration of hospitalization
      (4.1 vs 1.8 days) were significantly greater in cats with FO. Cats with FO were
      more likely to have received a fluid bolus (odds ratio [OR]: 5.1; 95% confidence
      interval [CI]: 1.3, 20, P = 0.014), developed a heart murmur (OR: 4.5; 95% CI,
      1.1-18, P = 0.028) or a gallop sound (OR: 75; 95% CI, 8.1-694, P < 0.0001).
      CONCLUSIONS: FO is a possible complication of the treatment of UO. The
      administration of a fluid bolus on presentation, and the development of a heart
      murmur or gallop sound during treatment were the most clinically useful risk
      factors identified. The development of FO is associated with significant
      increases in both the cost and length of hospitalization, but was not associated
      with increased mortality.

PMID- 28752929
TI  - Progesterone-mediated angiogenic activity of endothelial progenitor cell and
      angiogenesis in traumatic brain injury rats were antagonized by progesterone
      receptor antagonist.
AB  - OBJECTIVES: Progesterone (P4) has the potential therapeutic effects for traumatic
      brain injury (TBI) whose recovery depended on the enhanced angiogenesis.
      Endothelial progenitor cell (EPC) plays an essential role in vascular biology. We
      previously demonstrated that P4 administration improved circulating EPC level and
      neurological recovery of rat with TBI. Here, we hypothesized that P4 augmented
      angiogenic potential of EPC and the angiogenesis-related neurorestoration after
      TBI through classical progesterone receptor (PR). MATERIALS AND METHODS: EPC
      derived from rats were stimulated with graded concentrations (0, 10-10 , 10-9 , 5
      * 10-9 , 10-8 , 10-7  mol/L) of P4 or 10-6  mol/L ulipristal acetate (UPA, a PR
      antagonist). Male rats were subjected to cortical impact injury and treated with
      (i) DMSO (dimethyl sulfoxide), (ii) P4 and (iii) P4 and UPA. RESULTS: It showed
      that P4 improved the angiogenic potential of EPC, including tube formation,
      adhesion, migration and vascular endothelial growth factor secretion, in a dose
      dependent fashion with the maximal effect achieved at 10-9  mol/L P4. High
      concentration (10-7  mol/L) of P4 impaired the angiogenic potential of EPC.
      Notably, 10-6  mol/L UPA antagonized the stimulatory effects of 10-9  mol/L P4.
      After administrating P4, a significant improvement of neurological function and
      the restoration of the leaked blood-brain barrier were observed as well as a
      reduction of the brain water content. Both vessel density and expression of
      occludin of vessels were increased. When UPA was administered with P4, the neural
      restoration and angiogenesis were all reversed. Western blot showed that 10-9 
      mol/L P4 increased the content of PRA and PRB of EPC, while 10-7  mol/L P4
      reduced the content of both PR isoforms, but there was no change found in the TBI
      rats. CONCLUSIONS: It may suggest that P4-mediated angiogenic activity of EPC and
      angiogenesis in TBI rats were antagonized by PR antagonist.

PMID- 28752930
TI  - Oral administration of Grifola frondosa polysaccharides improves memory
      impairment in aged rats via antioxidant action.
AB  - SCOPE: Grifola frondosa is an edible/medicinal mushroom with great nutritional
      value and bioactivity. The present study was performed to evaluate the beneficial
      effect of polysaccharides isolated from Grifola frondosa on memory impairment in
      aged rats. METHODS AND RESULTS: 20-month-old rats were gavaged with Grifola
      frondosa polysaccharides (GFP) for 8 weeks. Morris Water Maze test revealed that
      GFP administration significantly improved memory impairment in aged rats. GFP
      supply was also found to attenuate age-associated changes of brain histology and
      ultrastructure observed by light microscopy and transmission electron microscopy.
      Moreover, the increase of total antioxidant capacity (T-AOC), glutathione
      peroxidase (GPx) activity, superoxide dismutase (SOD) activity, catalase (CAT)
      activity, as well as the decreased nitric oxide (NO) and malondialdehyde (MDA)
      levels, were consistent with the behavioral results. CONCLUSION: These findings
      indicated that oral administration of GFP could improve memory impairment via
      antioxidant action, and dietary supplementation with GFP may provide potential
      benefits on brain aging.

PMID- 28752931
TI  - Efficacy assessment of an intramammary treatment with a new recrystallized
      enrofloxacin vs ceftiofur and parenteral enrofloxacin in dairy cows with
      nonsevere clinical mastitis.
AB  - A recrystallized form of enrofloxacin as dehydrate-HCl (enro-C) was assessed for
      bacteriological and clinical cure efficacies in Holstein-Friesian cows affected
      of nonsevere clinical mastitis. Treatments were enro-Csusp (n = 81), treated with
      a pharmaceutical suspension of enro-C/quarter; group enro-Cpd (n = 80) treated as
      above, but using enro-C powder suspended in water; group CF (n = 65), treated
      with ceftiofur HCl/quarter; and group enroR (n = 66), treated with standard
      enrofloxacin solution (5 mg/kg, intramuscular). Cows had a mean milk production
      of 31 L/day and were 2-3 lactational periods old. Treatments were administered
      every 24 hr for 3 days. Groups treated with enro-C exhibited statistically
      significant (p > .05) better clinical cure as compared to groups treated with CF
      or enroR (95.06%, 96.25%, 67.79%, and 57.55%, for enro-Csusp , enro-Cpd , CF, and
      enroR , respectively). In contrast, probability of bacteriological cure was not
      statistically different among treatments. Yet, the outstanding clinical and
      bacteriological cure rates obtained for enro-C for nonsevere cases of mastitis is
      superior to previously reported data for parenteral enrofloxacin and other
      antibacterial-intramammary treatments. Impact of using enro-C on the rate and
      pattern of bacterial resistance, somatic cell counts and milk electric
      conductivity, must be studied. Also, the use of enro-C for complicated cases of
      mastitis should be studied and milk withdrawal times must be accurately
      established.

PMID- 28752932
TI  - Development of genotyping method for functionally relevant variants of
      cytochromes P450 in cynomolgus macaques.
AB  - In cynomolgus macaques (Macaca fascicularis), widely used in drug metabolism
      studies, CYP2C9, CYP2C76, CYP2D6, CYP3A4, and CYP3A5, important drug-metabolizing
      enzymes, are abundantly expressed in liver and metabolize cytochrome P450
      substrates. CYP2C9 (c.334A>C), CYP2C76 (c.449TG>A), CYP2D6 (c.891A>G), CYP3A4
      (IVS3 + 1G>del), and CYP3A5 (c.625A>T) substantially influence metabolic activity
      of enzymes, and thus are important variants in drug metabolism studies. In this
      study, a real-time PCR method was developed for genotyping these variants. The
      validity of the methods was verified by genotyping two wild type, two
      heterozygous, and two homozygous DNAs and was used to genotype 41 cynomolgus
      macaques (from Cambodia, Indonesia, the Philippines, or Vietnam) for the five
      variants, along with another important variant CYP2C19 (c.308C>T). The CYP2C9 and
      CYP2C19 variants were found only in Cambodian and Vietnamese animals, while the
      CYP2C76 and CYP2D6 variants were found only in Indonesian and Philippine animals.
      The CYP3A4 and CYP3A5 variants were not found in any of the animals analyzed.
      Mauritian animals, genotyped using next-generation sequencing data for
      comparison, possessed the CYP2C19 and CYP2D6 variants, but not the other
      variants. These results indicated differences in prevalence of these important
      variants among animal groups. Therefore, the genotyping tool developed is useful
      for drug metabolism studies using cynomolgus macaques.

PMID- 28752933
TI  - Reply.

PMID- 28752934
TI  - Electrocatalysts Derived from Metal-Organic Frameworks for Oxygen Reduction and
      Evolution Reactions in Aqueous Media.
AB  - Electrochemical energy conversion and storage devices such as fuel cells and
      metal-air batteries have been extensively studied in recent decades for their
      excellent conversion efficiency, high energy capacity, and low environmental
      impact. However, sluggish kinetics of the oxygen-related reactions at air
      cathodes, i.e., oxygen reduction reaction (ORR) and oxygen evolution reaction
      (OER), are still worth improving. Noble metals such as platinum (Pt), iridium
      (Ir), ruthenium (Ru) and their oxides are considered as the benchmark ORR and OER
      electrocatalysts, but they are expensive and prone to be poisoned due to the fuel
      crossover effect, and may suffer from agglomeration and leaching after long-term
      usage. To mitigate these limits, it is highly desirable to design alternative
      ORR/OER electrocatalysts with prominent performance. Metal-organic frameworks
      (MOFs) are a class of porous crystalline materials consisting metal ions/clusters
      coordinated by organic ligands. Their crystalline structure, tunable pore size
      and high surface area afford them wide opportunities as catalytic materials. This
      Review covers MOF-derived ORR/OER catalysts in electrochemical energy conversion,
      with a focus on the different strategies of material design and preparation, such
      as composition control and nanostructure fabrication, to improve the activity and
      durability of MOF-derived electrocatalysts.

PMID- 28752935
TI  - Synthesis of Water-Soluble Palladium Nanoparticles Stabilized by Sulfonated N
      Heterocyclic Carbenes.
AB  - A strategy involving the decomposition of palladium(II) organometallic complexes
      with sulfonated N-heterocyclic carbene ligands leads to the formation of stable
      and water-soluble Pd nanoparticles. Three different methodologies (thermal
      decomposition, reduction under 13 CO atmosphere, and reduction with H2 ) gave
      particles with different shapes and sizes, ranging from 1.5 to 7 nm. The
      structures of the organometallic intermediates and organic decomposition products
      were elucidated by NMR spectroscopy. To check the accessibility of the surface,
      the nanoparticles were tested as catalysts for the chemoselective hydrogenation
      of styrene in water. An effect of the particle size on the catalyst activity was
      observed. The aqueous phase was recycled up to ten times without any
      precipitation of metallic palladium.

PMID- 28752936
TI  - Environment and geographic distance differ in relative importance for determining
      fungal community of rhizosphere and bulk soil.
AB  - Rhizospheric fungi play major roles in both natural and agricultural ecosystems.
      However, little is known about the determinants of their diversity and
      biogeographic patterns. Here, we compared fungal communities in rhizosphere and
      bulk soils of wheat fields in the North China Plain. The rhizosphere had a lower
      fungal diversity (observed OTUs and Chao1) than bulk soil, and a distinct fungal
      community structure in rhizosphere compared with bulk soil. The relative
      importance of environmental factors and geographic distance for fungal
      distribution differed between rhizosphere and bulk soil. Environmental factors
      were the primary cause of variations in total fungal community and major fungal
      phyla in bulk soil. By contrast, fungal communities in soils loosely attached to
      roots were predictable from both environmental factors and influences of
      geographic distance. Communities in soils tightly attached to roots were mainly
      determined by geographic distance. Our results suggest that both contemporary
      environment processes (present-day abiotic and biotic environment characters) and
      historical processes (spatial isolation, dispersal limitation occurred in the
      past) dominate variations of fungal communities in wheat fields, but their
      relative importance of all these processes depends on the proximity of fungal
      community to the plant roots.

PMID- 28752937
TI  - Prediction of outcome in internet-delivered cognitive behaviour therapy for
      paediatric obsessive-compulsive disorder: A machine learning approach.
AB  - BACKGROUND: There are no consistent predictors of treatment outcome in paediatric
      obsessive-compulsive disorder (OCD). One reason for this might be the use of
      suboptimal statistical methodology. Machine learning is an approach to
      efficiently analyse complex data. Machine learning has been widely used within
      other fields, but has rarely been tested in the prediction of paediatric mental
      health treatment outcomes. OBJECTIVE: To test four different machine learning
      methods in the prediction of treatment response in a sample of paediatric OCD
      patients who had received Internet-delivered cognitive behaviour therapy (ICBT).
      METHODS: Participants were 61 adolescents (12-17 years) who enrolled in a
      randomized controlled trial and received ICBT. All clinical baseline variables
      were used to predict strictly defined treatment response status three months
      after ICBT. Four machine learning algorithms were implemented. For comparison, we
      also employed a traditional logistic regression approach. RESULTS: Multivariate
      logistic regression could not detect any significant predictors. In contrast, all
      four machine learning algorithms performed well in the prediction of treatment
      response, with 75 to 83% accuracy. CONCLUSIONS: The results suggest that machine
      learning algorithms can successfully be applied to predict paediatric OCD
      treatment outcome. Validation studies and studies in other disorders are
      warranted.

PMID- 28752938
TI  - Dendritic cells in hepatitis and liver transplantation.
AB  - Dendritic cells (DCs) play a key role in innate immune responses and are also the
      most effective cells for the activation of T cell immunity. They acquire antigen
      and process it; then they display it on the cell surface bound in a noncovalent
      complex with human leukocyte antigen molecules of class I (human leukocyte
      antigens A, B, and C) and class II (human leukocyte antigen DR). These cells are
      subdivided into 3 main subsets: 2 called myeloid dendritic cells (mDC) or
      classical DCs of types 1 and 2, and 1 called plasmacytoid dendritic cells (pDCs).
      The mDCs process and present antigen while the pDCs also strongly respond to
      viral signals by secreting type 1 interferon. In the liver, all of these subsets
      are present. However, their relative abundance is different from the peripheral
      blood, and it is further modified by liver disease. It appears that in relation
      to T cell tolerance, both mDCs and pDCs are influenced by the liver milieu and
      promote T cell inactivation. However, in antiviral responses and in
      ischemia/reperfusion injury, where innate immune functions are more important,
      mDCs and pDCs have distinct roles. Liver Transplantation 23 1433-1439 2017 AASLD.

PMID- 28752939
TI  - Effect of organic silicon, methylsulfonylmethane, and glucosamine sulfate in
      mandibular bone defects in rats.
AB  - Organic silicon (OS), glucosamine sulfate (GS), and methylsulfonylmethane (MSM)
      have been related to bone and connective tissue health and have been considered
      as basic therapy for osteoarthrosis disorders. Therefore, the aim was to analyze
      the effect of the association of these three components in mandibular bone
      defects in rats. Nine rats were used for histocompatibility test. In each animal
      was implanted the composition (70% OS, 15% GS, 15% MSM) and gutta percha
      (control) under the dorsal subcutaneous tissue. The samples were collected at 7,
      14, and 21 days post-surgery and inflammatory events analyzed. In sequence, the
      composition was engrafted in mandibular bone defects of nine rats; bone defects
      without treatment were the control group. Analyses were performed at 7, 14, and
      28 days post-surgery and samples were evaluated by scanning electron microscopy
      (SEM). For the histocompatibility test, both groups had a moderate inflammatory
      process at 7 days post-surgery and mild inflammatory process at 14 and 21 days.
      But in SEM analysis, the composition promotes an extensive reabsorption in
      cortical and crest alveolar bone, and great tooth root reabsorption. In
      conclusion, although the composition had positive result in the
      histocompatibility test, its direct application in mandibular bone defects caused
      intense resorption.

PMID- 28752940
TI  - Protective effects of in vivo-expressed autotransporters against Bordetella
      pertussis infection.
AB  - Bordetella pertussis causes whooping cough, a severe and prolonged respiratory
      disease that results inhas high morbidity and mortality rates, particularly in
      developing countries. The number incidence of whooping cough cases is increasing
      in many countries despite high vaccine coverage. Causes for the re-emergence of
      the disease include the limited duration of protection conferred by the acellular
      pertussis vaccines (aP)s and pathogenic adaptations that involve antigenic
      divergence from vaccine strains. Therefore, current vaccines therefore need to be
      improved. In the present study, we focused on five autotransporters: namely
      SphB1, BatB, SphB2, Phg, and Vag8, which were previously found to be expressed by
      B. bronchiseptica during the course of infection in rats and examined their
      protective efficiencies as vaccine antigens. The passenger domains of these
      proteins were produced in recombinant forms and used as antigens. An intranasal
      murine challenge assay showed that immunization with a mixture of SphB1 and Vag8
      (SV) significantly reduced bacterial load in the lower respiratory tract and a
      combination of aP and SV acts synergistically in effects of conferring protection
      against B. pertussis infection, implying that these antigens have potential as
      components to for improvinge th the currently available acellular pertussis
      vaccine.

PMID- 28752941
TI  - [Au(9-methylcaffein-8-ylidene)2 ]+ /DNA Tel23 System: Solution, Computational,
      and Biological Studies.
AB  - Physicochemical methods have been used to investigate interactions occurring in
      solution between the dicarbene gold(I) complex [Au(9-methylcaffein-8-ylidene)2
      ]BF4 (AuNHC) and a human telomeric DNA sequence, namely Tel23. Circular dichroism
      measurements allow identification of the conformational changes experienced by
      Tel23 upon interaction with AuNHC, and the respective binding stoichiometries and
      constants were determined. Computational studies provide a good link between
      previous crystallographic results of the same system and the present solution
      data, offering an exhaustive description of the inherent noncovalent metallodrug
      DNA interactions. Remarkably, we found that a preformed AuNHC/Tel23 adduct is
      capable of producing strong and selective inhibition of the enzyme telomerase.
      The latter feature is mechanistically relevant and might account for the
      conspicuous in vitro anticancer properties of the investigated dicarbene gold(I)
      complex.

PMID- 28752942
TI  - Phthaloyl-coenzyme A decarboxylase from Thauera chlorobenzoica: the prenylated
      flavin-, K+ - and Fe2+ -dependent key enzyme of anaerobic phthalate degradation.
AB  - The degradation of the industrially produced and environmentally relevant
      phthalate esters by microorganisms is initiated by the hydrolysis to alcohols and
      phthalate (1,2-dicarboxybenzene). In the absence of oxygen the further
      degradation of phthalate proceeds via activation to phthaloyl-CoA followed by
      decarboxylation to benzoyl-CoA. Here, we report on the first purification and
      characterization of a phthaloyl-CoA decarboxylase (PCD) from the denitrifying
      Thauera chlorobenzoica. Hexameric PCD belongs to the UbiD-family of
      (de)carboxylases and contains prenylated FMN (prFMN), K+ and, unlike other UbiD
      like enzymes, Fe2+ as cofactors. The latter is suggested to be involved in oxygen
      independent electron-transfer during oxidative prFMN maturation. Either oxidation
      to the Fe3+ -state in air or removal of K+ by desalting resulted in >92% loss of
      both, prFMN and decarboxylation activity suggesting the presence of an active
      site prFMN/Fe2+ /K+ -complex in PCD. The PCD-catalysed reaction was essentially
      irreversible: neither carboxylation of benzoyl-CoA in the presence of 2 M
      bicarbonate, nor an isotope exchange of phthaloyl-CoA with 13 C-bicarbonate was
      observed. PCD differs in many aspects from prFMN-containing UbiD-like
      decarboxylases and serves as a biochemically accessible model for the large
      number of UbiD-like (de)carboxylases that play key roles in the anaerobic
      degradation of environmentally relevant aromatic pollutants.

PMID- 28752943
TI  - Correlations between psychopathology and self-reported quality of life among
      adolescents in youth correctional facilities in Lagos, Nigeria: A short report.
AB  - BACKGROUND: The relationship between psychopathology and quality of life (QoL)
      and well-being among young incarcerated offenders has hardly been explored. AIMS:
      Our aim was to test the hypothesis that higher self-rated psychopathology would
      be associated with lower QoL among adolescents resident within youth correctional
      facilities in Lagos. METHODS: Psychopathology was assessed using the Strength and
      Difficulty Questionnaire (SDQ), while QoL was measured by using the Paediatric
      Quality of Life. RESULTS: One hundred and sixty-five adolescents completed the
      study, mostly boys (n = 124; 75%) with a mean age of 14.3 +/- 2.1 years. Nearly,
      a fifth (30, 18%) of respondents had abnormal total SDQ scores (>=17), suggestive
      of definite psychiatric disorder, while another 44 (27%) had highly probable
      psychopathology (total SDQ scores 15-16). There was strong negative correlation
      (r = -0.51, p < 0.001) between total SDQ scores and overall self-reported QoL
      among respondents. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Although we were
      unable to infer direction of relationship between psychopathology and QoL among
      these adolescents, it is plausible to suppose that treatment of mental health
      problems could have a positive impact on rehabilitation and reintegration. Given
      the rate of likely psychopathology, mental health screening within young offender
      institutions should be routine, and followed, as necessary with full assessment
      and resultant treatment. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28752944
TI  - Genomic divergence across ecological gradients in the Central African rainforest
      songbird (Andropadus virens).
AB  - The little greenbul, a common rainforest passerine from sub-Saharan Africa, has
      been the subject of long-term evolutionary studies to understand the mechanisms
      leading to rainforest speciation. Previous research found morphological and
      behavioural divergence across rainforest-savannah transition zones (ecotones),
      and a pattern of divergence with gene flow suggesting divergent natural selection
      has contributed to adaptive divergence and ecotones could be important areas for
      rainforests speciation. Recent advances in genomics and environmental modelling
      make it possible to examine patterns of genetic divergence in a more
      comprehensive fashion. To assess the extent to which natural selection may drive
      patterns of differentiation, here we investigate patterns of genomic
      differentiation among populations across environmental gradients and regions. We
      find compelling evidence that individuals form discrete genetic clusters
      corresponding to distinctive environmental characteristics and habitat types.
      Pairwise FST between populations in different habitats is significantly higher
      than within habitats, and this differentiation is greater than what is expected
      from geographic distance alone. Moreover, we identified 140 SNPs that showed
      extreme differentiation among populations through a genomewide selection scan.
      These outliers were significantly enriched in exonic and coding regions,
      suggesting their functional importance. Environmental association analysis of SNP
      variation indicates that several environmental variables, including temperature
      and elevation, play important roles in driving the pattern of genomic
      diversification. Results lend important new genomic evidence for environmental
      gradients being important in population differentiation.

PMID- 28752945
TI  - Synthesis of the compatible solute proline by Bacillus subtilis: point mutations
      rendering the osmotically controlled proHJ promoter hyperactive.
AB  - The ProJ and ProH enzymes of Bacillus subtilis catalyse together with ProA (ProJ
      ProA-ProH), osmostress-adaptive synthesis of the compatible solute proline. The
      proA-encoded gamma-glutamyl phosphate reductase is also used for anabolic proline
      synthesis (ProB-ProA-ProI). Transcription of the proHJ operon is osmotically
      inducible whereas that of the proBA operon is not. Targeted and quantitative
      proteome analysis revealed that the amount of ProA is not limiting for the
      interconnected anabolic and osmostress-responsive proline production routes. A
      key player for enhanced osmostress-adaptive proline production is the osmotically
      regulated proHJ promoter. We used site-directed mutagenesis to study the salient
      features of this stress-responsive promoter. Two important features were
      identified: (i) deviations of the proHJ promoter from the consensus sequence of
      SigA-type promoters serve to keep transcription low under non-inducing growth
      conditions, while still allowing a finely tuned induction of transcriptional
      activity when the external osmolarity is increased and (ii) a suboptimal spacer
      length for SigA-type promoters of either 16-bp (the natural proHJ promoter), or
      18-bp (a synthetic promoter variant) is strictly required to allow regulation of
      promoter activity in proportion to the external salinity. Collectively, our data
      suggest that changes in the local DNA structure at the proHJ promoter are
      important determinants for osmostress-inducibility of transcription.

PMID- 28752946
TI  - Coping experience of health concerns and physical disability for older Chinese
      people: A qualitative, descriptive study.
AB  - In this qualitative, descriptive study, we explored the perspectives of older,
      community-dwelling Chinese people regarding their experiences of coping with a
      physical disability and their health concerns. Twenty participants were
      interviewed in-depth, and data were analyzed using content analysis. Five themes
      with 13 subthemes emerged that described older people's experiences of coping
      with health concerns and disability: (i) ignoring health concerns; (ii) managing
      self; (iii) seeking medical help; (iv) living with physical disability; and (v)
      relying on limited resources. Most participants did not have sufficient access to
      health services due to physical disability and financial deficits, so they tended
      to ignore their health conditions or tackle them independently before seeking
      medical help. At the same time, they were impacted on by social and cultural
      factors. Policies are required that offer more resources to community-dwelling
      people with disabilities in China.

PMID- 28752947
TI  - Effectiveness of functional training on cardiorespiratory parameters: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Functional training is a new training vision that was prepared from
      the gesture imitation of daily activities. Although your use has become popular
      in clinical practice, the influence of the several cardiorespiratory adjustments
      performed during the functional training in different populations and conditions
      is unknown. So, the aim of this systematic review was to gather information in
      the literature regarding the influence of functional training on
      cardiorespiratory parameters. METHODS: We conducted search strategies on MEDLINE,
      PEDro, EMBASE, SportDiscus and Cochrane to identify randomized controlled trials
      investigating the effects of functional training on cardiorespiratory parameters.
      Methodological quality of the included studies was assessed using the PEDro
      scale. Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      summarized the evidence. RESULTS: Five original studies were included. Effects
      favoured functional training on oxygen consumption (VO2 ) at intermediate-term
      follow-up: weighted mean difference -1.0 (95% CI: 5.4-3.3), P = 0.642, and a
      small and not clinically important effect observed on VO2 favouring control at
      intermediate-term follow-up (i.e. mean difference of 1.30 (95% CI 1.07-1.53),
      P<0.001). CONCLUSION: According to the GRADE system, there is very low quality
      evidence that functional training is better than other interventions to improve
      cardiovascular parameters. This result encourages new searches about the theme.

PMID- 28752949
TI  - Haitian people's expectations regarding post-disaster humanitarian aid teams'
      actions.
AB  - The way people at the receiving end of humanitarian assistance perceive this
      intervention may provide invaluable bottom-up feedback to improve the quality of
      the intervention. We analyzed and mapped Haitians' views regarding international
      humanitarian aid in cases of natural disaster. Two hundred fifty participants-137
      women and 113 men aged 18-67-who had suffered from the consequences of the
      earthquake in 2010 were presented with a series of vignettes depicting a
      humanitarian team's action and were asked to what extent these actions
      corresponded to what ought to be expected from an international aid mission. Four
      factors were considered in the vignettes (a) whether the team worked in close
      association with local institutions, (b) whether it was composed of competent
      people who were prepared for their mission, (c) whether they treated people as a
      function of immediate needs, and (d) whether they behaved in a respectful way.
      Through cluster analysis, five qualitatively different positions were found: (a)
      Complete hostility to any kind of humanitarian aid (6%); (b) Strong hostility to
      humanitarian aid in the case of disrespectful attitudes or behaviors (4%); (c)
      Technical competence is the only factor that matters (25%); (d) Both
      manifestation of respect for the population and technical competence matter (38%)
      and (e) Undetermined (27%). Most Haitians expect humanitarian teams to be
      technically competent, but even very competent aid is not considered adequate if
      provided in an arrogant and disrespectful manner.

PMID- 28752948
TI  - Genomic insights into specialized metabolism in the marine actinomycete
      Salinispora.
AB  - Comparative genomics is providing new opportunities to address the diversity and
      distributions of genes encoding the biosynthesis of specialized metabolites. An
      analysis of 119 genome sequences representing three closely related species of
      the marine actinomycete genus Salinispora reveals extraordinary biosynthetic
      diversity in the form of 176 distinct biosynthetic gene clusters (BGCs) of which
      only 24 have been linked to their products. Remarkably, more than half of the
      BGCs were observed in only one or two strains, suggesting they were acquired
      relatively recently in the evolutionary history of the genus. These acquired gene
      clusters are concentrated in specific genomic islands, which represent hot spots
      for BGC acquisition. While most BGCs are stable in terms of their chromosomal
      position, others migrated to different locations or were exchanged with unrelated
      gene clusters suggesting a plug and play type model of evolution that provides a
      mechanism to test the relative fitness effects of specialized metabolites.
      Transcriptome analyses were used to address the relationships between BGC
      abundance, chromosomal position and product discovery. The results indicate that
      recently acquired BGCs can be functional and that complex evolutionary processes
      shape the micro-diversity of specialized metabolism observed in closely related
      environmental bacteria.

PMID- 28752951
TI  - Base-Free Asymmetric Transfer Hydrogenation of 1,2-Di- and Monoketones Catalyzed
      by a (NH)2 P2 -Macrocyclic Iron(II) Hydride.
AB  - The hydride isonitrile complex [FeH(CNCEt3 )(1 a)]BF4 (2) containing a chiral P2
      (NH)2 macrocycle (1 a), in the presence of 2-propanol as hydrogen donor,
      catalyzes the base-free asymmetric transfer hydrogenation (ATH) of prostereogenic
      ketones to alcohols and the hemihydrogenation of benzils to benzoins, which
      contain a base-labile stereocenter. Benzoins are formed in up to 83 % isolated
      yield with enantioselectivity reaching 95 % ee. Ketones give the same
      enantioselectivity observed with the parent catalytic system [Fe(CNCEt3 )2 (1 a)]
      (3 a) that operates with added NaOt Bu.

PMID- 28752950
TI  - Cell protrusion and retraction driven by fluctuations in actin polymerization: A
      two-dimensional model.
AB  - Animal cells that spread onto a surface often rely on actin-rich lamellipodial
      extensions to execute protrusion. Many cell types recently adhered on a two
      dimensional substrate exhibit protrusion and retraction of their lamellipodia,
      even though the cell is not translating. Travelling waves of protrusion have also
      been observed, similar to those observed in crawling cells. These regular
      patterns of protrusion and retraction allow quantitative analysis for comparison
      to mathematical models. The periodic fluctuations in leading edge position of XTC
      cells have been linked to excitable actin dynamics using a one-dimensional model
      of actin dynamics, as a function of arc-length along the cell. In this work we
      extend this earlier model of actin dynamics into two dimensions (along the arc
      length and radial directions of the cell) and include a model membrane that
      protrudes and retracts in response to the changing number of free barbed ends of
      actin filaments near the membrane. We show that if the polymerization rate at the
      barbed ends changes in response to changes in their local concentration at the
      leading edge and/or the opposing force from the cell membrane, the model can
      reproduce the patterns of membrane protrusion and retraction seen in experiment.
      We investigate both Brownian ratchet and switch-like force-velocity relationships
      between the membrane load forces and actin polymerization rate. The switch-like
      polymerization dynamics recover the observed patterns of protrusion and
      retraction as well as the fluctuations in F-actin concentration profiles. The
      model generates predictions for the behavior of cells after local membrane
      tension perturbations.

PMID- 28752952
TI  - Persistent diarrhea: a persistent infection with enteropathogens or a gut
      commensal dysbiosis?
AB  - In children from developing countries 5-10% of acute diarrhea (AD) episodes
      develop into persistent diarrhea (PD) defined by > 14 days of diarrhea duration.
      PD represents a major health burden leading to growth faltering. It is also
      associated with half of all diarrhea mortality. A rational intervention is thus
      crucial, but depends on an understanding of the pathogenesis of PD, which is
      still lacking. Many surveys were conducted in Latin America and in South Asia;
      they differ, however, with respect to enteropathogens associated with PD.
      Enteroaggregative strains of Escherichia coli (EAEC) were identified by several
      studies, but they may reflect selection by the frequent antibiotic use during the
      preceding AD episode. Epidemiologists have in fact identified antibiotic misuse
      as a major risk factor for PD. Together with the effectiveness of empirical
      treatment based on nutritional interventions with lactose-reduced and lactose
      free diets and particularly complex plant polysaccharides from green banana, one
      might suspect a role of commensal gut microbiota dysbiosis instead of a
      persistent infection with enteropathogens in many PD cases. An analysis of the
      commensal gut microbiota development in persistent diarrhea during nutritional
      interventions is likely to increase our understanding of PD pathogenesis.

PMID- 28752953
TI  - Evidence of microbial rhodopsins in Antarctic Dry Valley edaphic systems.
AB  - Microorganisms able to synthesize rhodopsins have the capacity to translocate
      ions through their membranes, using solar energy to generate a proton motive
      force. Rhodopsins are the most abundant phototrophic proteins in oceanic surface
      waters and are key constituents in marine bacterial ecology. However, it remains
      unclear how rhodopsins are used in most microorganisms. Despite their abundance
      in marine and fresh-water systems, the presence of functional rhodopsin systems
      in edaphic habitats has never been reported. Here, we show the presence of
      several new putative H+ , Na+ and Cl+ pumping rhodopsins identified by
      metagenomic analysis of Antarctic desert hypolithic communities. Reconstruction
      of two Proteobacteria genomes harboring xanthorhodopsin-like proteins and one
      Bacteroidetes genome with a Na-pumping-like rhodopsin indicated that these
      bacteria were aerobic heterotrophs possessing the apparent capacity for the
      functional expression of rhodopsins. The existence of these protein systems in
      hypolithic bacteria expands the known role of rhodopsins to include terrestrial
      environments and suggests a possible predominant function as heterotrophic energy
      supply proteins, a feasible microbial adaptation to the harsh conditions
      prevalent in Antarctic edaphic systems.

PMID- 28752954
TI  - Identification of GntR as regulator of the glucose metabolism in Pseudomonas
      aeruginosa.
AB  - In contrast to Escherichia coli, glucose metabolism in pseudomonads occurs
      exclusively through the Entner-Doudoroff (ED) pathway. This pathway, as well as
      the three routes to generate the initial ED pathway substrate, 6
      phosphogluconate, is regulated by the PtxS, HexR and GtrS/GltR systems. With GntR
      (PA2320) we report here the identification of an additional regulator in
      Pseudomonas aeruginosa PAO1. GntR repressed its own expression as well as that of
      the GntP gluconate permease. In contrast to PtxS and GtrS/GltR, GntR did not
      modulate expression of the toxA gene encoding the exotoxin A virulence factor.
      GntR was found to bind to promoters PgntR and PgntP and the consensus sequence of
      its operator was defined as 5'-AC-N-AAG-N-TAGCGCT-3'. Both operator sites
      overlapped with the RNA polymerase binding site and we show that GntR employs an
      effector mediated de-repression mechanism. The release of promoter bound GntR is
      induced by gluconate and 6-phosphogluconate that bind with similar apparent
      affinities to the GntR/DNA complex. GntR and PtxS are paralogous and may have
      evolved from a common ancestor. The concerted action of four regulatory systems
      in the regulation of glucose metabolism in Pseudomonas can be considered as a
      model to understand complex regulatory circuits in bacteria.

PMID- 28752955
TI  - Fibrobacter communities in the gastrointestinal tracts of diverse hindgut
      fermenting herbivores are distinct from those of the rumen.
AB  - The genus Fibrobacter contains cellulolytic bacteria originally isolated from the
      rumen. Culture-independent investigations have since identified Fibrobacter
      populations in the gastrointestinal tracts of numerous hindgut-fermenting
      herbivores, but their physiology is poorly characterized due to few
      representative axenic cultures. To test the hypothesis that novel Fibrobacter
      diversity exists in hindgut fermenters, we performed culturing and 16S rRNA gene
      amplicon sequencing on samples collected from phylogenetically diverse
      herbivorous hosts. Using a unique approach for recovering axenic Fibrobacter
      cultures, we isolated 45 novel strains from 11 different hosts. Full-length 16S
      rRNA gene sequencing of these isolates identified nine discrete phylotypes
      (cutoff = 0.03%) among them, including several that were only isolated from
      hindgut-fermenting hosts, and four previously unrepresented by axenic cultures.
      Our phylogenetic analysis indicated that six of the phylotypes are more closely
      related to previously described subspecies of Fibrobacter succinogenes, while the
      remaining three were more closely related to F. intestinalis. Culture-independent
      bacterial community profiling confirmed that most isolates were representative of
      numerically dominant phylotypes in their respective samples and strengthened the
      association of certain phylotypes with either ruminants or hindgut-fermenters.
      Despite considerable phylogenetic diversity observed among the Fibrobacter
      strains isolated here, phenotypic characterization suggests a conserved
      specialization for growth on cellulose.

PMID- 28752956
TI  - Black Phosphorus: Optical Characterization, Properties and Applications.
AB  - The rise of black phosphorus (BP) as a new family member of two-dimensional (2D)
      materials brings new concepts and applications to the field, because of the
      infrared band gap and anisotropic properties of such materials. Among many
      excellent properties of BP, the optical property attracts special attention in
      recent years. Optical methods have been widely and successfully used in
      characterizing BP, not only to obtain the structural information (such as
      thickness and crystalline orientation), but also to probe the fundamental
      properties of BP in terms of the behavior of electrons, phonons, excitons etc. In
      this Review, a comprehensive understanding about the optical characterization of
      BP such as Raman, absorption, and photoluminescence is presented. Also, the
      unique optical properties and applications explored in recent years are reviewed.

PMID- 28752957
TI  - Interacting effects of genetic variation for seed dormancy and flowering time on
      phenology, life history, and fitness of experimental Arabidopsis thaliana
      populations over multiple generations in the field.
AB  - Major alleles for seed dormancy and flowering time are well studied, and can
      interact to influence seasonal timing and fitness within generations. However,
      little is known about how this interaction controls phenology, life history, and
      population fitness across multiple generations in natural seasonal environments.
      To examine how seed dormancy and flowering time shape annual plant life cycles
      over multiple generations, we established naturally dispersing populations of
      recombinant inbred lines of Arabidopsis thaliana segregating early and late
      alleles for seed dormancy and flowering time in a field experiment. We recorded
      seasonal phenology and fitness of each genotype over 2 yr and several
      generations. Strong seed dormancy suppressed mid-summer germination in both early
      and late-flowering genetic backgrounds. Strong dormancy and late-flowering
      genotypes were both necessary to confer a winter annual life history; other
      genotypes were rapid-cycling. Strong dormancy increased within-season fecundity
      in an early-flowering background, but decreased it in a late-flowering
      background. However, there were no detectable differences among genotypes in
      population growth rates. Seasonal phenology, life history, and cohort fitness
      over multiple generations depend strongly upon interacting genetic variation for
      dormancy and flowering. However, similar population growth rates across
      generations suggest that different life cycle genotypes can coexist in natural
      populations.

PMID- 28752958
TI  - Increased Ca buffering underpins remodelling of Ca2+ handling in old sheep atrial
      myocytes.
AB  - KEY POINTS: Ageing is associated with an increased risk of cardiovascular disease
      and arrhythmias, with the most common arrhythmia being found in the atria of the
      heart. Little is known about how the normal atria of the heart remodel with age
      and thus why dysfunction might occur. We report alterations to the atrial
      systolic Ca2+ transient that have implications for the function of the atrial in
      the elderly. We describe a novel mechanism by which increased Ca buffering can
      account for changes to systolic Ca2+ in the old atria. The present study helps us
      to understand how the processes regulating atrial contraction are remodelled
      during ageing and provides a basis for future work aiming to understand why
      dysfunction develops. ABSTRACT: Many cardiovascular diseases, including those
      affecting the atria, are associated with advancing age. Arrhythmias, including
      those in the atria, can arise as a result of electrical remodelling or
      alterations in Ca2+ homeostasis. In the atria, age-associated changes in the
      action potential have been documented. However, little is known about remodelling
      of intracellular Ca2+ homeostasis in the healthy aged atria. Using single atrial
      myocytes from young and old Welsh Mountain sheep, we show the free Ca2+ transient
      amplitude and rate of decay of systolic Ca2+ decrease with age, whereas
      sarcoplasmic reticulum (SR) Ca content increases. An increase in intracellular Ca
      buffering explains both the decrease in Ca2+ transient amplitude and decay
      kinetics in the absence of any change in sarcoendoplasmic reticulum calcium
      transport ATPase function. Ageing maintained the integrated Ca2+ influx via ICa-L
      but decreased peak ICa-L . Decreased peak ICa-L was found to be responsible for
      the age-associated increase in SR Ca content but not the decrease in Ca2+
      transient amplitude. Instead, decreased peak ICa-L offsets increased SR load such
      that Ca2+ release from the SR was maintained during ageing. The results of the
      present study highlight a novel mechanism by which increased Ca buffering
      decreases systolic Ca2+ in old atria. Furthermore, for the first time, we have
      shown that SR Ca content is increased in old atrial myocytes.

PMID- 28752959
TI  - Genetic variations in toll-like receptors 7 and 8 modulate natural hepatitis C
      outcomes and liver disease progression.
AB  - BACKGROUND & AIMS: The natural outcomes of hepatitis C virus (HCV) as well as the
      progression of the liver disease are highly variable and depend primarily on an
      efficient immune response. As toll-like receptors seven (TLR7) and eight (TLR8)
      are important effectors of the innate immunity, this study aims to evaluate the
      association between TLR7 and TLR8 polymorphisms and the HCV infection outcomes in
      Moroccan subjects. METHODS: In this case-control study, 643 subjects including
      293 mild chronic hepatitis patients, 119 with advanced liver disease (AdLD), 93
      with HCV spontaneous clearance and 138 healthy controls were genotyped using
      TaqMan SNPs assays. RESULTS: Patients carrying TLR7 rs179008-A allele were more
      likely to clear the virus spontaneously (P = .0001 for women, and P < .001 for
      men). Besides, carriage of TLR7 rs179009-A allele was associated with a twofold
      increase in spontaneous viral clearance in female patients (P = .0002), but not
      in men. In addition, we observed that TLR7 rs179008-T and rs179009-G alleles
      increased the risk of disease progression in both sexes (P < .05). TLR8 rs3764880
      G allele was associated with spontaneous HCV clearance in both sexes (P < .0001)
      albeit with an apparently stronger association in males (OR = 6.02 for men vs 2.2
      for women). In males, TLR8 rs3764879-C and TLR8 rs3764880-A alleles were
      significantly associated with AdLD status (P < .05). CONCLUSIONS: Our results
      suggest that variations in TLR7 and TLR8 genes modulate the clearance and
      progression of HCV infection with different magnitudes between sexes. Our results
      refine, therefore, our understanding of the sex-specific differences observed
      regarding the susceptibility to chronic hepatitis.

PMID- 28752960
TI  - After successful hepatitis C virus antiviral therapy: It looks that normal
      alanine aminotransferase level is not the normal.
AB  - BACKGROUND: Normal serum alanine aminotransferase (ALT) levels differ with age,
      gender, and body mass index. Adjusting the upper limits of normal (ULN) for ALT
      needs further research in different populations. Aim of this work was to monitor
      the effect of successful chronic hepatitis C (CHC) treatment on the ALT levels in
      patients with normal pretreatment ALT. METHODS: Data of 1160 CHC patients with
      persistent pretreatment normal liver enzymes were retrospectively analyzed.
      Treatment response to direct acting antiviral agents (DAAs) therapy was recorded.
      Changes in ALT levels before and after treatment were analyzed by patients'
      demographic, laboratory, and radiologic characteristics. Areas under the receiver
      operating characteristic curve (AUROC) of ALT after treatment were used to
      generate a new ALT ULN. RESULTS: Males were 568 (49%) and females 592 (51%) with
      a mean age of 50.7 years. After treatment, mean (+/-SD) of ALT levels
      significantly decreased from (26.3+/-7.8) to (19.1+/-10.9). This reduction was
      more significant in interferon-free than interferon-based regimens. ROC curve
      analyses suggested a new ALT ULN cut off (26.4 IU/L) in the treated patients
      (sensitivity=78.6%, specificity=83.8%, AUROC=0.89. This cutoff dropped to 14.7
      IU/L in cirrhotic patients (sensitivity=77.4%, specificity=44.7%, AUROC=0.612).
      The identified cutoffs were 16.3 IU/L (sensitivity=66.7%, specificity=47.5%,
      AUROC=0.499) and 15.5 IU/L (sensitivity=76.5%, specificity=51.3%, AUROC=0.576) in
      males and females, respectively. CONCLUSION: The current ALT ULN needs
      readjustment to identify new normal cutoffs in CHC patients. Posttreatment
      cutoffs differ according to gender, pretreatment liver affection, and treatment
      regimen.

PMID- 28752961
TI  - Symbiont dynamics and strain diversity in the defensive mutualism between Lagria
      beetles and Burkholderia.
AB  - Defensive mutualisms are often facultative in nature, and their evolutionary
      dynamics can be shaped by changes in local antagonist communities or arms races
      with coevolving antagonists. Under these conditions, selection may favour hosts
      that flexibly acquire symbionts producing compounds with bioactivity against
      current antagonists. Here, we study the prevalence, dynamics and strain diversity
      of Burkholderia gladioli bacteria in Lagria beetles, a recently described
      protective symbiosis involving vertical transmission and antifungal defense for
      the host eggs. In Lagria hirta, we investigate the fate of the bacteria during
      the host life cycle. Despite a transmission route relying solely on the females,
      the bacteria are present in both sexes during the larval stage, suggesting a
      potentially multifaceted defensive role. In L. hirta and L. villosa adults,
      culture-dependent and -independent techniques revealed that individual beetles
      harbour diverse Burkholderia strains from at least two different phylogenetic
      clades, yet all closely related to free-living B. gladioli. Interestingly,
      rearing the beetles in the laboratory strongly impacted symbiont strain profiles
      in both beetle species. Our findings highlight the dynamic nature of the B.
      gladioli-Lagria symbiosis and present this as a valuable system for studying
      multiple strain coinfections, as well as the evolutionary and ecological factors
      regulating defensive symbiosis.

PMID- 28752962
TI  - Seabirds (Laridae) as a source of Campylobacter spp., Salmonella spp. and
      antimicrobial resistance in South Africa.
AB  - Zoonotic thermophilic Campylobacter and nontyphoidal Salmonella enterica are a
      major cause of foodborne human gastroenteritis worldwide. There is little
      information about reservoirs of these zoonotic agents in Africa. Thus, chicks of
      kelp gulls (Larus dominicanus, n = 129) and greater crested terns (Thalasseus
      bergii, n = 100) were studied at five colonies on the Western Cape coast (South
      Africa) during summer 2013/2014. Campylobacter spp. occurrence was 14.0% (CI95% :
      9.9-19.3), with C. jejuni the most frequently isolated species, whilst that of
      Salmonella was 27.5% (CI95% : 21.9-33.9) overall, with a higher prevalence in
      gulls (43.0%, CI95% : 34.8-52.4) than terns (7.0%, CI95% : 3.1-14.4). Among the
      16 different S. enterica serovars found, Anatum, Enteritidis and Hadar were the
      most frequent. The same or highly similar pulsed-field gel electrophoresis
      genotype was found in some Salmonella isolates from seabirds and humans
      presenting with salmonellosis in Cape Town hospitals. Both Campylobacter and
      Salmonella isolates exhibited antimicrobial resistance to several agents,
      including critically important antimicrobials (quinolones, tetracyclines and beta
      lactams) and multidrug resistance in Salmonella serovars from kelp gulls. Our
      results highlight the importance of seabirds as reservoirs of Campylobacter and
      Salmonella resistant strains and their role in the maintenance and transmission
      of these bacteria in the environment, with implications for public health.

PMID- 28752963
TI  - Systematic genetic dissection of chitin degradation and uptake in Vibrio
      cholerae.
AB  - Vibrio cholerae is a natural resident of the aquatic environment, where a common
      nutrient is the chitinous exoskeletons of microscopic crustaceans. Chitin
      utilization requires chitinases, which degrade this insoluble polymer into
      soluble chitin oligosaccharides. These oligosaccharides also serve as an inducing
      cue for natural transformation in Vibrio species. There are 7 predicted
      endochitinase-like genes in the V. cholerae genome. Here, we systematically
      dissect the contribution of each gene to growth on chitin as well as induction of
      natural transformation. Specifically, we created a strain that lacks all 7
      putative chitinases and from this strain, generated a panel of strains where each
      expresses a single chitinase. We also generated expression plasmids to
      ectopically express all 7 chitinases in our chitinase deficient strain. Through
      this analysis, we found that low levels of chitinase activity are sufficient for
      natural transformation, while growth on insoluble chitin as a sole carbon source
      requires more robust and concerted chitinase activity. We also assessed the role
      that the three uptake systems for the chitin degradation products GlcNAc,
      (GlcNAc)2 and (GlcN)2 , play in chitin utilization and competence induction.
      Cumulatively, this study provides mechanistic details for how this pathogen
      utilizes chitin to thrive and evolve in its environmental reservoir.

PMID- 28752964
TI  - Differential accumulation of vimentin fragments in preeclamptic placenta.
AB  - Preeclampsia is a pregnancy complication that is the result of abnormal
      placentation because of inadequate trophoblast invasion into spiral arteries that
      prevent normal blood flow to the placenta. We report the alteration in vimentin
      protein proteolysis in placenta of normotensive and preeclamptic women, which is
      known to have a role in many physiological functions other than its major
      function in the structural integrity of the cell. Placental proteome from
      normotensive (n = 25) and preeclamptic pregnancies (n = 25) showed eight
      differentially accumulated protein spots of vimentin (proteolytic fragments) by
      two-dimensional electrophoresis. Immunoblots of normotensive and preeclamptic
      placenta revealed a difference in proteolytic processing of vimentin. In
      particular, lower molecular weight vimentin fragments of 32 and 20 kDa were 3.3
      and 2.6-fold (p < 0.0001) higher, respectively, in preeclampsia compared with
      normotensive placenta.

PMID- 28752965
TI  - [The Effect of Sodium Ferulate in Experimental Pulmonary Fibrosis via NALP3
      Inflammasome].
AB  - OBJECTIVE: To investigate the activation of NALP3 inflammasome in the process of
      experimental pulmonary fibrosis (PF), and evaluate the effect of sodium ferulate
      (SF) in the relationship of NALP3 and PF. METHODS: Establishing PF experimental
      model via bleomycin (BLM) intratracheal injection (BLM group, SF group), treated
      with SF daily (SF group) or PBS [BLM group, control (CON) group] and mice were
      executed on day 21. Ashcroft score was used to assess lung fibrosis in mice PF
      model. The content of hydroxyproline (HYP) in lung tissue was determined by
      alkaline hydrolysis. Fibroblast NIH-3T3 was treated with H2O2 to trigger cell
      oxidative stress in vitroexperiments (H2O2group). Cell was pre-administrated with
      SF 2 h before H2O2 stimulation in H2O2+SF group. Blank group without any
      treatments, was set as control. Real time-PCR was used to investigate the
      expressions of three elements of inflammasome[NALP3, caspase-1, apoptosis
      associated speck-like protein (ASC)], collagen-1 and alpha smooth muscle actin
      (alpha-SMA) mRNA in both lung tissue and fibroblast. Western blot was used to
      detect protein level of NALP3 in mice lung tissue and collagen-1, alpha-SMA in
      fibroblast as well. Meanwhile, IL-1beta content in lung tissue and cell
      supernatant was measured by ELISA. RESULTS: in vitro experiment, SF treated mice
      showed lower Ashcroft score and HYP content and decreased NALP3, ASC, caspase-1
      mRNA expressions and IL-1beta production, NALP3 protein level compared with BLM
      group (P<0.05). in vitroexperiment, H2O2 increased NALP3 (P<0.05), ASC (P<0.01),
      caspase-1 (P<0.05) expressions and IL-1beta releasing (P<0.05)and promoted the
      expressions of collagen-1 and alpha-SMA in both gene and protein levels (P<0.05)
      in NIH-3T3. NALP3 activation was partly inhibited in H2O2+SF group (P<0.05). The
      mRNA expression levels of collagen-1 and alpha-SMA were reduced in H2O2+SF group
      (P<0.05) and the protein expressions of alpha-SMA and collagen-1 were decreased
      (P<0.05) compared with those of H2O2 group. CONCLUSION: Sodium ferulate may
      suppress oxidative stress mediated NALP3 activation to inhibit fibroblast
      activation in the anti-fibrosis effect.

PMID- 28752966
TI  - [The Study of the Effect and Mechanism of Glucagon Like Peptide-1 in Bleomycin
      induced Pulmonary Fibrosis in Mice].
AB  - OBJECTIVE: To investigate the potential value and mechanisms of glucagon like
      peptide-1 (GLP-1) on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS:
      Mice were treated with a single sublethal dose of BLM (3 mg/kg ) via
      intratracheal infusion to produce pulmonary fibrosis, and then liraglutide (2
      mg/kg) was given to the mice for 28 days by intraperitoneal injection. 28 days
      after BLM infusion, the number of total cells, macrophages and neutrophils,
      lymphocytes, and the content of transforming growth factor-beta 1 (TGF-beta1) in
      bronchoalveolar lavage fluid (BALF) were measured. Hematoxylin-eosin (HE)
      staining and Masson's trichrome (MT) staining were performed. The Ashcroft score
      and hydroxyproline content were analyzed. Real time(RT)-qPCR and Western blot
      were used to evaluate the expression of alpha-smooth muscle actin (alpha-SMA) and
      vascular cell adhesion molecule-1 (VCAM-1). The phosphorylation of nuclear factor
      kappa B (NF-kappaB) p65 was also assessed by Western blot. DNA binding of NF
      kappaB p65 was measured through TransAMTMNF-kappaB p65 transcription factor ELISA
      kit. RESULTS: GLP-1 reduced inflammatory cells infiltration and the content of
      TGF-beta1 in BLAF in mice with BLM injection. The Ashcroft score and
      hydroxyproline content were decreased by GLP-1 administration. Meanwhile, BLM
      induced overexpression of alpha-SMA and VCAM-1 were blocked by GLP-1 treatment in
      mice. GLP-1 also reduced the ratio of phospho-NF-kappaB p65/total-NF-kappaB p65
      and NF-kappaB p65 DNA binding activity in BLM-induced pulmonary fibrosis in mice.
      CONCLUSION: BLM-induced lung inflammation and pulmonary fibrosis were
      significantly alleviated by GLP-1 treatment in mice, possibly through
      inactivation of NF-kappaB.

PMID- 28752967
TI  - [Expression of HSP70 in Kunming Mouse Embryos Stimulated by Chronic Mild
      Anticipatory Stress].
AB  - OBJECTIVE: To measure the expression of heat shock protein 70 (HSP70) in mice
      embryos with the stimulation of chronic mild anticipatory stress (CUMS) to female
      Kunming mice. METHODS: Three hundreds female Kunming mice were stressed by 9
      chronic mild unpredictable stress factors for 28 days and then divided into three
      groups of mild, moderate and severe stress. PMSG/hCG was measured to assess the
      induction of superovulation, and ovarian response and embryo development
      potential were observed. The expression of HSP70 in 2-cell embryos and day 4
      embryos was detected by immunofluorescence and real time polymerase chain
      reaction (RT-PCR). RESULTS: After 28 d CUMS stimulation, the rate of mice in
      mild, moderate and severe stress were 50%, 32% and 18%, respectively. In the mild
      stress group, ovarian response and oocyte development potential were similar to
      those of control, while HSP70 expression of the embryos was significantly higher
      (P<0.05). In the severe stress group, ovarian response and oocyte development
      potential were significantly decreased compared with the control group (P<0.05),
      while HSP70 expression was similar to that of control. CONCLUSION: HSP70
      overexpression observed in the embryos may be related to its proteetive effect
      against chronic unpredictable stress.

PMID- 28752968
TI  - [Effects of Triptolide on the Autophagy in Synovial, Spleen and Thymus of Rats
      with Adjuvant Arthritis].
AB  - OBJECTIVE: To determine the effect of triptolide (TP) on the expression of ATG
      /LC3-II Beclin1 in synovial, spleen, and thymusof rats with adjuvant arthritis
      (AA). METHODS: Rats were divided for four groups: normal control (NC), model
      control (MC), leflunomide (LEF) treatment, and triptolide (TP)treatment, with 12
      rats in each group.The AA model was established through Freund's complete
      adjuvant (0.1 mL each) injection into the right foot plantar skin to introduce
      inflammation and 10 days of tail root injection of 0.05 mL Freund's complete
      adjuvant for immunity strengthening. Drug administration started 13 days after
      induction of inflammation. Rats in the NC and MC groups were given normal saline
      (1 mL/100 g) once a day for 30 days, compared with 5 mg/kg of oral LEF for the
      rats in the LEF group and 50 MUg/kg of oral TP for the rats in the TP group. Paw
      swelling (E), joint arthritis index(AI) and joint pathological changes of the
      rats were recorded. The serum expressions of cytokines B lymphocyte stimulating
      factor (BAFF), interleukin (IL)-1, tumor necrosis factor (TNF) alpha, IL-15,and
      IL-10 were detected by ELISA. The expressions of Atg5, Atg7, and Atg12 mRNA in
      synovial, spleen, and thymus of the rats were detected by RT-PCR.The expressions
      of LC3-II and Beclin1 in synovial, spleen, and thymus of the rats were detected
      by Western blot assay. RESULTS: The AA model rats had lower serum BAFF, IL-1, TNF
      alpha, IL-15, and IL-10; lower Atg5and Atg12 mRNA in synovial; lower Atg5 mRNA,
      Atg7, and Atg12 mRNA in spleen; higher Atg12 mRNA in thymus; and lower LC3-II and
      Beclin1 in synovial, spleen and thymus(P<0.05 or 0.01). TP treatment led to
      reduced paw swelling and arthritis index; declined Atg7 and Atg12 mRNA in
      synovial; declined Atg5, Atg7 mRNA and Atg12 mRNA in spleen; decreased Atg5 and
      Atg7mRNA in thymus; increased Atg12 mRNA in thymus; and increased LC3-II and
      Beclin1 in synovial, spleen and thymus (P<0.05 or 0.01). Compared with rats
      treated with LEF, TP treated rats had lower TNF-alpha and BAFF and higher E and
      IL-15 (P<0.05 or 0.01); as well as decreased expressions of Atg7 mRNA (synovial)
      and Atg5, Atg7 mRNA (thymus), and increased expressions of Atg12 mRNA (thymus)
      and Atg5, Atg7, Atg12 mRNA (spleen). CONCLUSION: TP regulates autophagy in
      synovial, thymus and spleen of AA rats, and improves theirjointinflammatory
      response.

PMID- 28752969
TI  - [Investigation the Inhibitory Effects of Kaempferol on Rat Renalmesangial Cells
      Proliferation under High Glucose Condition].
AB  - OBJECTIVE: To investigate the protective effects of kaempferol on rat renal
      mesangial cells under high glucose condition and explore its mechanism. METHODS:
      The HBZY-1 cells were divided into normal glucose group (5.5 mmol/L), high
      glucose group (25 mmol/L), 10 MUmol/L kaempferol+high glucose group, and 30
      MUmol/L kaempferol+high glucose group. Cell proliferative ability was measured by
      MTT; cell cycle was analyzed by flow cytometry; mRNA and protein levels were
      determined by Real-time PCR and Western blot, respectively. RESULTS: Kaempferol
      had no effect on the proliferative ability of rat renal mesangial cells under
      normal glucose (5.5 mmol/L) condition. High glucose (25 mmol/L) enhanced the cell
      proliferative ability, and this effect was antagonized by kaempferol (10-30
      MUmol/L) treatment. High glucose reduced the cell population at G0/G1 phase with
      an associated increase in S phase, and had no effect on G2/M phase; and
      kaempferol treatment restored high glucose-induced changes in cell cycle.
      Kaempferol also prevented high glucose-induced increase in fibronectin and
      connective tissue growth factor mRNA and protein expression levels. Kaempferol
      also prevented high glucose-induced increase in fibronectin and connective tissue
      growth factor mRNA and protein expression levels. Further, high glucose caused an
      increase in protein level of phosphorylated p38 mitogen-activated protein kinases
      (p38 MAPK), which was antagonized by kaempferol treatment. CONCLUSION: Our
      results suggest that kaempferol exerts its protective effect on rat renal
      mesangial cells under high glucose condition via p38 MAPK signaling pathway.

PMID- 28752970
TI  - [Trans-differentiation of Human Amniotic Epithelial Cells into Follicle-like
      Structure].
AB  - OBJECTIVE: To determine whether hAECs can differentiate into follicle-like
      structure. METHODS: hAECs were isolated from human term placenta and cultured
      sequentially in medium supplemented with 5% human follicular fluid. The
      morphology of the cells was examined by inverted microscope. Changes of estradiol
      levels and expressions of germ cell specific gene in the cultured medium were
      detected by chemiluminescence immunoassay and Real time-Polymerase Chain Reaction
      (RT-PCR), respectively. RESULTS: Oocyte-like cells (OLCs) were found in those
      cultured in the medium supplemented with 5% human follicular fluid. The OLCs
      gradually aggrandized, shrunk and finally disappeared over time. However, this
      phenomenon was not observed in the control group. Higher expressions
      ofDAZLandGDF9were found in the follicle group compared with the control which
      medium without 5% human follicular fluid (P< 0.05), with two peaks. No
      significant difference in the expression ofSCP3was found between the two groups
      (P>0.05). Estradiol was detected in the culture medium of the follicle group in a
      mode of decreasing-rising-decreasing, but not in the control group. CONCLUSION:
      hAECs have the potential to trans-differentiate into the follicle-like structure
      in vitro.

PMID- 28752971
TI  - [Effects of Low-magnitude Whole Body Vibration (WBV) on Knee Osteoarthritis in
      Rabbits].
AB  - OBJECTIVE: To determine the effects of low-magnitude whole body vibration (WBV)
      on the structure and function of subchondral trabecular bones, cartilage
      degradation, bone/cartilage turnover, and osteoarthritis (OA) joint function.
      METHODS: Knee osteoarthritis model was established in 96 rabbits through left
      anterior cruciate ligament transaction (ACLT). The rabbits were randomly divided
      into six groups: ACLT control group, WBV+ACLT group (five subgroups, each
      comprising 16 rabbits receiving 5 Hz, 10 Hz, 20 Hz, 30 Hz and 40 Hz WBV,
      respectively, with 2-4 mm amplitude for 40 min/d and 5 d/week over a period of 8
      weeks). Joint function was tested via weight-bearing asymmetry. The
      microarchitecture of subchondral trabecular bones was examined using vivo micro
      computed tomography (micro-CT). Cartilage samples from knee joints were taken for
      gross morphology and histology examinations. Serum samples were taken to detect
      cartilage oligomeric matrix protein (COMP), C-terminal telopeptide of type I
      collagen (CTX)-I and urine CTX-II. RESULTS: Knee joint pain decreased with 10 Hz
      (P<0.05) and 20 Hz WBV treatment (P<0.05) , but increased with 40 Hz treatment
      (P<0.05). The micro-CT results showed that articular cartilage increased first,
      peaked at 20 Hz, and then decreased (P<0.05) . With increased frequency of WBV,
      the trabecular number, subchondral bone thickness and bone volume fraction
      increased, serum CTX-I decreased, COMP and CTX-II increased, especially at 20 Hz
      (P<0.05). CONCLUSION: Lower frequency (20 Hz) WBV can improve bone
      microstructure, increase bone turnover, delay cartilage degeneration and improve
      limb function of rabbits with OA.

PMID- 28752972
TI  - [The Inhibitory Effect and Mechanism of Human Umbilical Cord Mesenchymal Stem
      Cells on Prostate Cancer Metastasis].
AB  - OBJECTIVE: To test whether umbilical cord mesenchymal stem cells (UMSCs) can
      inhibit the growth and metastasis of prostate cancer cells, and to investigate
      the mechanism. METHODS: The UMSCs from human umbilical cord tissue were isolate
      by explant technique. After being co-cultured the UMSCs with LNCaP and PC-3 cells
      for 24 h, 48 h and 72 h, LNCaP and PC-3 cells' proliferation were tested and the
      72 h proliferation inhibitory rate (IR) was calculated. Transwell invasion assay
      was used to test the migration and invasion abilities of prostate cancer cells
      after being co-cultured with UMSCs for 48 h. The invasion IR were calculated. The
      expression of matrix metalloproteinases (MMP)-2, MMP-9, tissue inhibitor of
      metalloproteinase (TIMP)-1 and TIMP-2 in the 72 h co-culture supernatants were
      tested by MILLIPLEX(r)MAPmethod. RESULTS: The proliferation of prostate cancer
      cells was inhibited after being co-cultured with UMSCs. The proliferation rate of
      LNCaP was lower than control group at 72 h (P<0.05), and the proliferation IR was
      37.21%. The proliferation rate of PC-3 was lower than control group at 48 h and
      72 h (P<0.05), and the proliferation IR was 31.27% at 72 h. Transwell invasion
      assays showed that co-culturing 48 h with UMSCs inhibited the invasive abilities
      of LNCaP and PC-3, and the invasion IR were 48.35% (LNCaP) and 46.91% (PC-3). Co
      culturing 72 h, the expression of MMP-2 and MMP-9 were down-regulated (P<0.05)
      and the secretion of TIMP-1 and TIMP-2 were up-regulated (P<0.05) compared with
      control group. CONCLUSION: UMSCs can inhibit the proliferation and invasion
      abilities of prostate cancer cells by secreting TIMPs, the antagonist of MMPs,
      which suppressed the overexpression of MMPs.

PMID- 28752973
TI  - [Differences of Therapeutic Efficacy Between Different Kinds of Somatostatin
      Analogue for Primary Hepatocellular Carcinoma].
AB  - OBJECTIVE: To explore the effects of SOM230, octreotide and lanreotide on
      hepatocellular carcinoma cell line Bel-7402 In vivoand In vitro, and to analyze
      the differences of their therapeutic efficacy with relevant mechanisms. METHODS:
      At different time points (24, 48, 72 h), the cell counting kit-8 (CCK8) was used
      to evaluate cell proliferation (drug concentration 1*10-10-1*10-5mol/L) and the
      Annexin V-FITC/PI staining was used to assess cell apoptosis (drug concentration
      1*10-5mol/L), while the real-time quantitative PCR was used to detect cellular
      SSTRexpression changes before and after interventions. A transplanted tumor model
      was set up, and the tumor-bearing nude mice were treated by three drugs with a
      common dose of 100 MUg/ (kg.d) or same volume of normal saline, respectively.
      After a treatment period of 6 weeks, real-time quantitative PCR and Western blot
      test were performed to detect the expression changes ofSSTR in tumor tissues from
      the level of gene and protein. RESULTS: All three drugs could inhibit the cell
      proliferation of Bel-7402. However, they were unable to promote the cell
      apoptosis. In vitro, the expressions ofSSTR1, SSTR4genes did not change over time
      in each group. The expressions ofSSTR2gene were decreased in three intervention
      groups while the expressions ofSSTR5gene were increased first and then decreased.
      Compared with the control group, all differences have statistical significance
      (P<0.05). All three drugs could improve the survival rate and quality of life for
      nude mice bearing hepatoma. In vivo, the expression ofSSTR1gene in SOM230 group
      was increased when compared with that of the other groups; the expressions
      ofSSTR2gene in three intervention groups were increased when compared with that
      of the control group; the expressions of SSTR5gene in SOM230 group and lanreotide
      group were increased when compared with that of the octreotide group and the
      control group, and all differences have statistical significance (P<0.05). The
      Western blot test confirmed these results from the protein level. CONCLUSION: In
      a certain concentration range, the long-term treatment of SSTA with high
      affinities to SSTR2 and SSTR5 could inhibit the growth of HCC.

PMID- 28752974
TI  - [Effects of Neurotrophin Receptor-interacting MAGE Homolog on Apoptosis of
      Intestinal Epithelial Cells].
AB  - OBJECTIVE: To explore whether neurotrophin receptor-interacting MAGE homolog
      (NRAGE) is involved in the intestinal ischemia-reperfusion (I/R) and its effect
      on the apoptosis of intestinal epithelial cells and the expression of occludin
      protein. METHODS: The level of NRAGE protein after the rat small intestine I/R
      was detected by immunohistochemical (IHC) In vivo. The level of NRAGE protein and
      mRNA in IEC-6 cells after hypoxia and reoxygenation were tested by Western blot
      and RT-PCR respectively in vitro. The IEC-6 cells were divided into four groups,
      including NRAGE overexpression by lentivirus infection (Lv-NRAGE group),
      interference (sh-NRAGE group), lentivirus control (Lv-control group), and normal
      control group without lentivirus infection (NC group). The apoptosis of IEC-6
      cells after infection was analyzed by flow cytometry. The level of the tight
      junction protein occludin was detected by Western blot. RESULTS: The expression
      of NRAGE were highly increased in intestinal mucosa epithelial cells after I/R
      (P<0.01). The proteins and mRNA levels of NRAGE were increased after 6 h of
      hypoxia in IEC-6 cellsin vitro. Compared with the Lv-control group, the early
      apoptosis rate was raised (P<0.01) and the level of occludin was reduced (P<0.01)
      in Lv-NRAGE group; while the early apoptosis rate was reduced (P<0.01) and the
      level of occludin was raised in sh-NRAGE group(P<0.001). CONCLUSION: NRAGE may be
      involved in intestinal I/R and promote the apoptosis and decrease occludin
      expression of intestinal epithelial cells.

PMID- 28752975
TI  - [Assessing Cardiac Function of Patients with Chronic Kidney Disease using N
      Terminal Pro-brain Natriuretic Peptide Precursor (NT-proBNP)].
AB  - OBJECTIVE: To determine the plasma level of N-terminal brain natriuretic peptide
      precursor (NT-proBNP) in patients with chronic kidney disease (CKD) and its
      association with cardiac function. METHODS: A total of 567 CKD patients admitted
      to the hospital from January 2013 to December 2014 were divided into six groups
      according to their estimated glomerular filtration rate. Their plasma level of NT
      proBNP, renal function, and cardiac function were determined. RESULTS: The worse
      patients cardiac function, and the lower eGFR, the higher concentration of plasma
      NT-proBNP. Plasma level of NT-proBNP was negatively correlated with glomerular
      filtration rate (=-0.529, P<0.01). The receiver operating characteristic curves
      generated a cutoff NT-proBNP value of 119.5 ng/L, 168.5 ng/L, 300.5 ng/L, 1 019.5
      ng/L, 2 777.5 ng/L, and 3 640.5 ng/L, respectively, for diagnosing cardiac
      failure in the six groups, respectively. CONCLUSION: NT-proBNP is affected by
      renal function, which can be used for diagnosing cardiac failure in patients with
      CKD.

PMID- 28752976
TI  - [Difference of Liver Enzymes in Different Metabolism States of Chronic Hepatitis
      B].
AB  - OBJECTIVE: To analyze the difference of liver enzymes in different metabolism
      state groups of chronic hepatitis B (CHB). METHODS: We use prospective cross
      sectional study to analyze the difference of liver enzymes in different
      metabolism state groups in 110 cases of CHB, including alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and glutamyl
      transferase (GGT). RESULTS: Regardless of the presence or absence of fatty liver,
      the levels of ALP and GGT were increased along with the deterioration of glucose
      metabolism (P<0.05).The levels of ALP and GGT in the presence of fatty liver
      group were higher than those in the absence of fatty liver group (P<0.05). The
      levels of AST, ALP and GGT showed the trend of increasing along with the increase
      of HOMA-IR and the decrease of HOMA-beta. There was no difference of liver
      enzymes among the groups with or without other metabolism disorder (P>0.05).
      CONCLUSION: In CHB, abnormal glucose metabolism and fatty liver can lead to the
      increase of ALP and GGT. The increase of HOMA-IR and the decrease of HOMA-beta
      may lead to the increase of AST, ALP and GGT. Other metabolism disorder did not
      show any effect on the level of liver enzymes.

PMID- 28752977
TI  - [Correlation Between Dietary Nutrition and Premature Ovarian Failure].
AB  - OBJECTIVE: To explore the relationship between dietary nutrition and premature
      ovarian failure (POF). METHODS: A case control study was undertaken in 294
      patients recruited from the reproductive endocrine clinic of our hospital over
      the period from November 2015 to January 2017. The POF group included women with
      premature ovarian failure , and women with normal menstruation were included as
      control group. The dietary and nutritional status of these patients were analyzed
      and compared. RESULTS: A total of 70 POF patients (POF group) and 224 controls
      participated in this study. No significant differences in age, sex, height, body
      mass and body mass index (BMI) existed between the two groups. Significant
      differences were found between the two groups in daily intakes of protein,
      carbohydrate and dietary fiber (P<0.05). Low carbohydrate (OR=11.652, 95% CI:
      3.864-35.135) and dietary fiber intake (OR=7.851, 95% CI: 2.272-27.137) were
      associated with higher odds of POF. CONCLUSION: Deficiencies of carbohydrate and
      dietary fiber are associated with premature ovarian failure.

PMID- 28752978
TI  - [Application of Competing Risks Model in Predicting Smoking Relapse Following
      Ischemic Stroke].
AB  - OBJECTIVE: To determine factors associated with smoking relapse in men who
      survived from their first stroke. METHODS: Data were collected through face to
      face interviews with stroke patients in the hospital, and then repeated every
      three months via telephone over the period from 2010 to 2014. Kaplan-Meier method
      and competing risk model were adopted to estimate and predict smoking relapse
      rates. RESULTS: The Kaplan-Meier method estimated a higher relapse rate than the
      competing risk model. The four-year relapse rate was 43.1% after adjustment of
      competing risk. Exposure to environmental tobacco smoking outside of home and
      workplace (such as bars and restaurants) (P=0.01), single (P<0.01), and prior
      history of smoking at least 20 cigarettes per day (P=0.02) were significant
      predictors of smoking relapse. CONCLUSION: When competing risks exist, competing
      risks model should be used in data analyses. Smoking interventions should give
      priorities to those without a spouse and those with a heavy smoking history.
      Smoking ban in public settings can reduce smoking relapse in stroke patients.

PMID- 28752979
TI  - [Sleep Duration and Abdominal Obesity in Elderly in China].
AB  - OBJECTIVE: To determine the relationship between sleep duration and abdominal
      obesity in elderly in china. METHODS: Data were drawn from the 2013 China Health
      and Retirement National Investigation (China Health and Retirement Longitudinal
      Study, CHARLS). The prevalence of abdominal obesity in the elderly who had a
      normal range of sleep duration was compared with those who had a shorter or
      longer sleep duration using Chi-square tests and binary logistic regression
      models. RESULTS: Higher odds of abdominal obesity were found in the elderly male
      with a shorter (OR=1.627, 95%CI: 1.286-2.060, P<0.05) or longer (OR=1.499, 95%CI:
      1.009-2.228, P<0.001) sleep duration, compared with those with a normal range of
      sleep duration. Statistical significances were found in the prevalence of
      abdominal obesity among those with different characteristics in education,
      smoking, chronic conditions, and social participation. CONCLUSION: Both long and
      short sleep durations are associated with increased risk of obesity, which is
      more evident in older men. Bad living habits and mental state will increase the
      risk of abdominal obesity.

PMID- 28752980
TI  - [Ultrasonic Features of Enthesitis: a Comparison Between Patients with Psoriasis
      Vulgaris and Patients with Psoriatic Arthritis].
AB  - OBJECTIVE: To compare the ultrasonic features of enthesitis between psoriatic
      arthritis and psoriasis vulgaris. METHODS: A total of 39 patients with psoriatic
      arthritis (PsA group), 60 with psoriasis vulgaris (non-PsA group) and 60 healthy
      people (control group) participated in this study. They were examined by two
      dimensional and color Doppler ultrasound on the entheses of bilateral femoral
      quadriceps tendons, patella tendons, Achilles tendons, plantar fasciae, common
      flexor tendons and common extensor tendons. RESULTS: About 45% (27 cases) healthy
      controls had enthesitis, with Achilles tendons and femoral quadriceps tendons
      being most likely affected. No blood flow signal was observed on the affected
      sites. About 63% (38 cases) of non-PsA patients had enthesitis, with Achilles
      tendons and femoral quadriceps tendons being most likely affected. Blood flow
      signals were observed on 4 affected sites. More than 84% (33 cases) PsA patients
      had enthesitis, with all locations being likely affected but mostly on Achilles
      tendons, femoral quadriceps tendons, and plantar fasciae. Blood flow signals were
      observed on 18 affected sites. The differences in prevalence of enthesitis were
      statistically significant (PsA group>non-PsA group>control group, all P<0.01),
      although the differences in tendon hypoechogenicity and enthesophytes among the
      groups showed no statistical significance. PsA and non-PsA patients were more
      likely to have tendon thickening than the controls (both P<0.01); but no
      difference appeared between PsA and non-PsA patients. PsA patients had higher
      prevalence of intratendinous calcifications, bony erosions and color Doppler
      signals than non-PsA patients and the controls (all P<0.01). CONCLUSION:
      Enthesitis in healthy people and non-PsA patients are most likely to affect
      Achilles tendon and femoral quadriceps tendons. By contrast, Achilles tendons,
      femoral quadriceps tendon and plantar fascia are more likely to be affected in
      patients with PsA. PsA patients have high prevalence of enthesitis and are more
      likely to have intratendinous calcifications, bony erosions and color Doppler
      signals.

PMID- 28752981
TI  - [Ultrasonographic Features of Hepatic Epithelioid Hemangioendothelioma on B-mode
      and Contrast-enhanced Ultrasound].
AB  - OBJECTIVE: To investigate the ultrasonographic features of hepatic epithelioid
      hemangioendothelioma (HEHE) on B-mode and contrast-enhanced ultrasound (CEUS).
      METHODS: From January 2012 to September 2016, 17 patients with surgery or biopsy
      confirmed HEHE were retrospectively analyzed for their clinical history,
      ultrasonographic data of B-mode ultrasound and CEUS characteristics. RESULTS: The
      mean age of the 17 patients was (42.88+/-13.95) yr. (range 23-69 yr.). On B-mode
      ultrasound, 6 case (6/17, 35.3%) were single lesion, while 11 case (11/17, 64.7%)
      had multiple lesions, of which 10 cases involved the global liver. There were
      88.2% of lesions (15/17) located underneath the liver capsule, and 94.1% of
      lesions (16/17) with regular shape. The mean diameter of the lesions was (3.93+/
      2.23) cm. The lesions appeared as hypoechoic (13/17, 76.5%), hyperechoic (1/17,
      5.9%) and mixed-echoic (3/17, 17.6%). 7 patients underwent CEUS, 5 of them (5/7,
      71.4%) showed a rim-like hyperenhancement in arterial phase while the other 2
      presented overall hyperenhancement of the lesions with uneven perfusion inside.
      All cases demonstrated hypoenhancement in portal and delay phases. CONCLUSION:
      Multiple subcapsular hypoechoic focal liver lesions with regular shape remind of
      the possibility of HEHE. CEUS could provide considerable value in its diagnosis.

PMID- 28752982
TI  - [Sample Size Calculation using SAS for PhaseIIin Two-stage Clinical Trials of
      Anti-tumor Drugs].
AB  - OBJECTIVE: To compare Gehan two-stage design and Simon two-stage design in sample
      size calculations for phase II clinical trials of anti-tumor drugs. METHODS: We
      explained the sample size calculation methods with a single-stage design, Gehan
      two-stage design, and Simon optimal two-stage and minimax two-stage designs in
      line with the principle of exact binomial probability. By setting up different
      parameters in SAS macro program, the advantages and disadvantages of these
      designs were compared. RESULTS: The minimax two-stage design does not increase
      the maximum sample size compared with the single-stage design. Compared with the
      Gehan two-stage design, the Simon two-stage design has the advantage of being
      able to determine an early termination of trials when no or low anti-tumor
      activities are evident. CONCLUSION: Simon two-stage design is better than single
      stage design and Gehan two-stage design. The minimax design is more popular than
      the optimal design.

PMID- 28752983
TI  - [Detection of Circulating Tumor Cells in Bladder Cancer by Subtraction Enrichment
      and Immunostaining-fluorescence in situ Hybridization].
AB  - OBJECTIVE: To detect circulating tumor cells (CTCs) in peripheral blood from the
      patients with bladder cancer using subtraction enrichment and immunostaining
      fluorescence in situ hybridization (SE-iFISH) and to explore the relation between
      CTCs detection result and the clinicpathological parameters of tumors. METHODS:
      Sixteen patients [(66.88+/-8.97) yr.] with bladder cancerwere included, whlile 10
      normal people [(61.90+/-9.13) yr.] were enrolled as control. Peripheral blood was
      harvested (6 mL per case) for the detection of CTCs with the method of
      subtraction enrichment and SE-iFISH, and the correlations of CTCs level to the
      clinicpathological parameters of tumors were analyzed, including hematuria, size,
      number, NMIBC or MIBC, stage, grade and pathological type. RESULTS: Positive
      rates of CTCs in experimental and control group were 43.75% (7/16) and 0% (0/10),
      respectively. The difference was statistically significant (P=0.022 7). The
      number of CTCS was not associated with the clinicpathological parameters of
      bladder cancer, which probably due to small sample size. CONCLUSION: It is
      applicable to detect CTCs of bladder cancer by SE-iFISH.

PMID- 28752984
TI  - [Ultrasound Manifestations of Eyes of Pediatric Patients with Morning Glory
      Syndrome].
AB  - OBJECTIVE: To analyze ultrasonic manifestations of eyes of pediatric patients
      with morning glory syndrome (MGS). METHODS: Clinical data and ultrasound (US)
      findings for six children (4 males and 2 females, 5-60 months old) diagnosed with
      MGS between 2005 and 2016 were reviewed. RESULTS: Of the 12 eyes, seven were
      diagnosed with MGS; one with cataract; the other four were normal. One child had
      both eyes diagnosed with MGS. Of the seven eyes with MGS (5 right, 2 left), one
      was small associated with persistent hyperplastic primary vitreous (PHPV); 2 had
      retinal detachment. Findings of high frequency ultrasound included local anechoic
      lesions with distinct boundary showing a convert bottle-neck shape that appeared
      in the area of optic disk of posterior pole. The lesions communicated with the
      vitreous caicy and extended to the optic nerves. The lesions had a maximum depth
      of 4-15 mm [(8.29+/-4.42) mm] and a maximum width of 4-11 mm [(6.86+/-2.67) mm].
      Hypoecho material was found in the bottom of five of the seven lesions. The
      distance between the end of the optic nerves and the bottom of the lesions ranged
      from 0 to 4.5 mm. Lower levels (Adler 0-1 grade) of blood flow in the bottom of
      the lesions were found compared with those (3-5 grade) in the rim of the lesions.
      CONCLUSION: MGS is rare and usual occurs in young children, especially infants.
      It is often associated with various eye complications. The ultrasound
      manifestations of MGS are characterized with a local anechoic lesion mimicking a
      convert bottle-neck shape in the area of optic disk of posterior pole.

PMID- 28752985
TI  - Considerations in minimally invasive adrenal surgery: the frontdoor or the
      backdoor?
AB  - Over the last few decades, in the field of minimally invasive adrenal surgery,
      retroperitoneoscopic adrenalectomy (PRA) has shown favorable results when
      compared to laparoscopic transperitoneal adrenalectomy (LTA). However, for many
      endocrine surgeons it is unclear if, when, and how to transition from LTA to PRA.
      Although the length of the learning curve for both approaches is comparable, the
      LTA is a technically more challenging procedure whilst PRA demands an orientation
      in a new environment in a patient that is positioned upside down. Visiting a
      proctor is crucial for successfully adopting the PRA procedure, and continued
      mentorship in a surgeon's own hospital during the first procedures is preferable.
      There are several other aspects related to the decision to transition to PRA; the
      caseload of adrenal patients, learning aspects of other members of the team,
      technical considerations, case selection, and a well-developed emergency plan in
      case of complications during surgery. In a dedicated endocrine center with a
      considerable annual case load of approximately 30 procedures, we recommend to
      transition to PRA in order to provide the highest quality of care to adrenal
      patients.

PMID- 28752986
TI  - Analysis of medium-long-term therapeutic effect of PCM artificial cervical disc
      replacement.

PMID- 28752987
TI  - Recent perspectives of pediatric probiotic supplementation.

PMID- 28752988
TI  - Role of a behavioural therapy involving psychodrama for the treatment of sleep
      disorders in paediatric primary care.
AB  - BACKGROUND: Sleep disorders are common in young children. Our objective was to
      describe a psychodrama using puppets and to assess the interest of this approach
      for the treatment of sleep disorders in ambulatory paediatric patients. METHODS:
      This retrospective, observational, monocentre study was carried between 1st
      January 2014 and 31st December 2015. Children aged 12 months to 6 years with a
      sleep disorder confirmed according to the International Classification of Sleep
      Disorders-2 were recruited. The parents were questioned separately about their
      child's sleep rhythm and the family's quality of life (QoL). The child sitting on
      their parent's knee and, using puppets to represent the family members, the
      paediatrician reproduced the scenario that took place at home and demonstrated
      what should be changed. The parents were contacted by telephone 1-2 weeks after
      the therapy to determine whether the child's sleep patterns had improved. The
      primary endpoint was resolution of the sleep disorder. RESULTS: Thirty-eight
      children (mean age 27.2 +/- 14.0 months; mean duration of sleep disorder 12.7 +/-
      9.5 months) were assessed. The most common sleep disorders were difficulties in
      falling asleep at evening bed-time (76.3%) and night-time wakening (76.3%). The
      main triggering factors were the birth of a sibling (30.8%) or an illness
      (30.8%). In the majority (52.2%) of families who were convinced that the
      psychodrama would work, an immediate and complete resolution of the sleep
      disorder was obtained within 3 days of the consultation. QoL improved in the
      majority of families after the consultation (QoL was average in 68.4% of families
      before the consultation vs. good in 84.2% after the consultation). Psychodrama
      was effective at bringing about an immediate and complete resolution of sleep
      disorders in children. This confirms the findings of other reports that show that
      behavioural therapy is effective in this context. CONCLUSIONS: This method could
      be adapted effectively by individual practitioners, enabling children to
      establish a good sleep pattern without the use of medications. A further large
      scale, randomised, controlled trial is required to confirm these results.

PMID- 28752989
TI  - 2H -> 1T Phase Change in Direct Synthesis of WS2 Nanosheets via Solution-Based
      Electrochemical Exfoliation and Their Catalytic Properties.
AB  - Metallic 1T-WS2 has various interesting properties such as increased density of
      catalytically active sites on both the basal planes and edges as well as metallic
      conductivity which allows it to be used in applications such as biosensing and
      energy devices. Hence, it is highly beneficial to develop a simple, efficient,
      and low-cost synthesis method of 1T-WS2 nanosheets from commercially available
      bulk 2H-WS2. In this study, we reported WS2 nanosheets synthesized directly from
      bulk WS2 via solution-based electrochemical exfoliation with bipolar electrodes
      and investigated their electrocatalytic performances toward hydrogen evolution
      and oxygen reduction reactions. We successfully synthesized WS2 nanosheets of
      regular hexagonal symmetry with a 2H -> 1T phase transition. This represents a
      novel method of producing 1T-WS2 nanosheets from bulk 2H-WS2 without compromising
      on its electrocatalytic properties.

PMID- 28752990
TI  - Quartz Crystal Microbalance Assay of Clinical Calcinosis Samples and Their
      Synthetic Models Differentiates the Efficacy of Chelation-Based Treatments.
AB  - This paper sets out in vitro protocols for studying the relative effectiveness of
      chelators used in the dissolution-based treatment of hard calcinosis. Pulverized
      hard calcinosis samples from human donors or synthetic hydroxyapatite
      nanoparticles were deposited by electrophoretic deposition on the surface of a
      quartz crystal microbalance sensor. Over 150 deposits of <20 MUg were dissolved
      over the course of 1 h by aliquots of buffered, aqueous solutions of two calcium
      chelators, EDTA and citrate, with the surface-limited dissolution kinetics
      monitored with <1 s time resolution. There was no statistically significant
      difference in dissolution rate between the four synthetic hydroxyapatite
      materials in EDTA, but the dissolution rates in citrate were lower for
      hydroxyapatite produced by acetate or nitrate metathesis. Hard calcinosis and
      synthetic hydroxyapatites showed statistically identical dissolution behavior,
      meaning that readily available synthetic mimics can replace the rarer samples of
      biological origin in the development of calcinosis treatments. EDTA dissolved the
      hydroxyapatite deposits more than twice as fast as citrate at pH 7.4 and 37 
      degrees C, based on a first-order kinetic analysis of the initial frequency
      response. EDTA chelated 6.5 times more calcium than an equivalent number of moles
      of citrate. Negative controls using nonchelating N,N,N',N'
      tetraethylethylenediamine (TEEDA) showed no dissolution effect. Pharmaceutical
      dissolution testing of synthetic hydroxyapatite tablets over 6 h showed that EDTA
      dissolved the tablets four to nine times more quickly than citrate.

PMID- 28752991
TI  - Entry of a Six-Residue Antimicrobial Peptide Derived from Lactoferricin B into
      Single Vesicles and Escherichia coli Cells without Damaging their Membranes.
AB  - Lactoferricin B (LfcinB) and shorter versions of this peptide have antimicrobial
      activity. However, the elementary processes of interactions of these peptides
      with lipid membranes and bacteria are still not well understood. To elucidate the
      mechanism of their antimicrobial activity, we investigated the interactions of
      LfcinB (4-9) (its sequence of RRWQWR) with Escherichia coli cells and giant
      unilamellar vesicles (GUVs). LfcinB (4-9) and lissamine rhodamine B red-labeled
      LfcinB (4-9) (Rh-LfcinB (4-9)) did not induce an influx of a membrane-impermeant
      fluorescent probe, SYTOX green, from the outside of E. coli cells into their
      cytoplasm, indicating that no damage occurred in their plasma membrane. To
      examine the activity of LfcinB (4-9) to enter E. coli cytoplasm, we investigated
      the interaction of Rh-LfcinB (4-9) with single cells of E. coli containing
      calcein using confocal microscopy. We found that Rh-LfcinB (4-9) entered the
      cytoplasm without leakage of calcein. Next, we investigated the interactions of
      Rh-LfcinB (4-9) with single GUVs of dioleoylphosphatidylglycerol (DOPG) and
      dioleoylphosphatidylcholine (DOPC) mixtures containing a fluorescent probe, Alexa
      Fluor 647 hydrazide (AF647), using the single GUV method. The results indicate
      that Rh-LfcinB (4-9) outside the GUV translocated through the GUV membrane and
      entered its lumen without leakage of AF647. Interaction of Rh-LfcinB (4-9) with
      DNA increased its fluorescence intensity greatly. Therefore, we can conclude that
      Rh-LfcinB (4-9) can translocate across lipid membrane regions of the plasma
      membrane of E. coli cells to enter their cytoplasm without leakage of calcein and
      its antimicrobial activity is not due to damage of their plasma membranes.

PMID- 28752992
TI  - Structure and Biophysics for a Six Letter DNA Alphabet that Includes Imidazo[1,2
      a]-1,3,5-triazine-2(8H)-4(3H)-dione (X) and 2,4-Diaminopyrimidine (K).
AB  - A goal of synthetic biology is to develop new nucleobases that retain the
      desirable properties of natural nucleobases at the same time as expanding the
      genetic alphabet. The nonstandard Watson-Crick pair between imidazo[1,2-a]-1,3,5
      triazine-2(8H)-4(3H)-dione (X) and 2,4-diaminopyrimidine (K) does exactly this,
      pairing via complementary arrangements of hydrogen bonding in these two
      nucleobases, which do not complement any natural nucleobase. Here, we report the
      crystal structure of a duplex DNA oligonucleotide in B-form including two
      consecutive X:K pairs in GATCXK DNA determined as a host-guest complex at 1.75 A
      resolution. X:K pairs have significant propeller twist angles, similar to those
      observed for A:T pairs, and a calculated hydrogen bonding pairing energy that is
      weaker than that of A:T. Thus, although inclusion of X:K pairs results in a
      duplex DNA structure that is globally similar to that of an analogous G:C
      structure, the X:K pairs locally and energetically more closely resemble A:T
      pairs.

PMID- 28752993
TI  - Effects of MgO and SiO2 on Plasma-Sprayed Hydroxyapatite Coating: An in Vivo
      Study in Rat Distal Femoral Defects.
AB  - Plasma-sprayed hydroxyapatite (HA)-coated titanium implants have been widely used
      in orthopedic applications due to their inheritance of an excellent mechanical
      property from titanium and great osteoconductivity from HA. However, the lack of
      osteoinductivity limits their further applications. In this study, 1 wt % MgO and
      0.5 wt % SiO2 were mixed with HA for making plasma-sprayed coatings on titanium
      implants. Plasma-sprayed HA- and MgO/SiO2-HA-coated titanium implants showed
      adhesive bond strengths of 25.73 +/- 1.92 and 23.44 +/- 2.89 MPa, respectively.
      The presence of MgO and SiO2 significantly increased the osteogenesis,
      osseointegration, and bone mineralization of HA-coated titanium implants by the
      evaluation of their histomorphology after 6, 10, and 14 weeks of implantation in
      rat distal femoral defects. Implant pushout tests also showed a shear modulus of
      149.83 +/- 3.69 MPa for MgO/SiO2-HA-coated implants after 14 weeks of
      implantation, compared to 52.68 +/- 10.41 MPa for uncoated implants and 83.92 +/-
      3.68 MPa for pure HA-coated implants; These are differences in the shear modulus
      of 96% and 56.4%, respectively. This study assesses for the first time the
      quality of the bone-implant interface of induction plasma-sprayed MgO and SiO2
      binary-doped HA coatings on load-bearing implants compared to bare titanium and
      pure HA coatings in a quantitative manner. Relating the osseointegration and
      interface shear modulus to the quality of implant fixation is critical to the
      advancement and implementation of HA-coated orthopedic implants.

PMID- 28752994
TI  - Mo6+ Doping in Li3VO4 Anode for Li-Ion Batteries: Significantly Improve the
      Reversible Capacity and Rate Performance.
AB  - Consider the almost insulator for pure Li3VO4 with a band gap of 3.77 eV, to
      significantly improve the electrical conductivity, the novel Li3V1-xMoxO4 (x =
      0.00, 0.01, 0.02, 0.05, and 0.10) anode materials were prepared successfully by
      simple sol-gel method. Our calculations show that, by substitute Mo6+ for V5+,
      the extra electron occupied the V 3p empty orbital and caused the Fermi level
      shift up into the conduction band, where the Mo-doped Li3VO4 presents electrical
      conductor. The V/I curve measurements show that, by Mo doping in V site, the
      electronic conductivity of the Li3VO4 was increased by 5 orders of magnitude. And
      thence the polarization was obviously reduced. EIS measurement results indicated
      that by Mo-doping a higher lithium diffusion coefficient can be obtained. The
      significantly increased electronic conductivity combined the higher lithium
      diffusion coefficient leads to an obvious improvement in reversible capacity and
      rate performance for the Mo-doped Li3VO4. The resulting Li3V1-xMoxO4 (x = 0.01)
      material exhibited the excellent rate capability. At a high rate 5 C, a big
      discharge capacity of the initial discharge capacity 439 mAh/g can be obtained,
      which is higher than that of pure Li3VO4 (only 166 mAh/g), and after 100 cycles
      the mean capacity fade is only 0.06% per cycle.

PMID- 28752995
TI  - Bioinspired Polymer Systems with Stimuli-Responsive Mechanical Properties.
AB  - Materials with switchable mechanical properties are widespread in living
      organisms and endow many species with traits that are essential for their
      survival. Many of the mechanically morphing materials systems found in nature are
      based on hierarchical structures, which are the basis for mechanical robustness
      and often also the key to responsive behavior. Many "operating principles"
      involve cascades of events that translate cues from the environment into changes
      of the overall structure and/or the connectivity of the constituting building
      blocks at various levels. These concepts permit dramatic property variations
      without significant compositional changes. Inspired by the function and the
      growing understanding of the operating principles at play in biological materials
      with the capability to change their mechanical properties, significant efforts
      have been made toward mimicking such architectures and functions in artificial
      materials. Research in this domain has rapidly grown in the last two decades and
      afforded many examples of bioinspired materials that are able to reversibly alter
      their stiffness, shape, porosity, density, or hardness upon remote stimulation.
      This review summarizes the state of research in this field.

PMID- 28752996
TI  - One-Step Printable Perovskite Films Fabricated under Ambient Conditions for
      Efficient and Reproducible Solar Cells.
AB  - Despite the potential of roll-to-roll processing for the fabrication of
      perovskite films, the realization of highly efficient and reproducible perovskite
      solar cells (PeSCs) through continuous coating techniques and low-temperature
      processing is still challenging. Here, we demonstrate that efficient and reliable
      CH3NH3PbI3 (MAPbI3) films fabricated by a printing process can be achieved
      through synergetic effects of binary processing additives, N-cyclohexyl-2
      pyrrolidone (CHP) and dimethyl sulfoxide (DMSO). Notably, these perovskite films
      are deposited from premixed perovskite solutions for facile one-step processing
      under a room-temperature and ambient atmosphere. The CHP molecules result in the
      uniform and homogeneous perovskite films even in the one-step slot-die system,
      which originate from the high boiling point and low vapor pressure of CHP.
      Meanwhile, the DMSO molecules facilitate the growth of perovskite grains by
      forming intermediate states with the perovskite precursor molecules.
      Consequently, fully printed PeSC based on the binary additive system exhibits a
      high PCE of 12.56% with a high reproducibility.

PMID- 28752997
TI  - Synthesis and Characterization of Ultrathin Silver Sulfide Nanoplatelets.
AB  - We report the synthesis of ultrathin silver sulfide (Ag2S) nanoplatelets (NPLs)
      synthesized via a one-pot method in ethylene glycol with 3-mercaptopropionic acid
      serving as both the sulfur precursor and the platelet ligand. The colloidally
      synthesized nanoplatelets are exceptionally thin, with a thickness of only 3.5 +/
      0.2 A and a 1S exciton Bohr diameter to confinement ratio of ~12.6. The NPL
      growth is shown to be quantized by layer thickness using absorption and
      photoluminescence (PL) spectroscopy. Transmission electron microscopy, atomic
      force microscopy, and X-ray diffraction analyses of the NPLs show that they
      correspond to the (202) plane of the beta-Ag2S structure. The PL quantum yield of
      these NPLs is ~30%, suggesting their potential use in biomedical imaging.
      Optoelectronic properties were evaluated via sensitized photocurrent spectroscopy
      with the resulting spectra closely matching the distinctive absorption spectral
      shape of the Ag2S NPLs.

PMID- 28752998
TI  - Complex Stability During the Transport Cycle of a Subclass I ECF Transporter.
AB  - The mechanism of energy-coupling factor (ECF) transporters, a special type of ATP
      binding-cassette importers for micronutrients in prokaryotes, is a matter of
      controversial discussion. Among subclass II ECF transporters, a single ECF
      interacts with several substrate-binding integral membrane proteins (S units) for
      individual solutes. Release and catch of the S unit, previously observed
      experimentally for a subclass II system, was proposed as the mechanism of all ECF
      transporters. The BioM2NY biotin transporter is a prototype of subclass I
      systems, among which the S unit is dedicated to a specific ECF. Here we simulated
      the transport cycle using purified BioM2NY in detergent solution. BioM2NY
      complexes were stable during all steps. ATP binding was a prerequisite for biotin
      capture and ATP hydrolysis for subsequent biotin release. The data demonstrate
      that S units of subclass I ECF transporters do not have to dissociate from
      holotransporter complexes for high-affinity substrate binding, indicating
      mechanistic differences between the two subclasses.

PMID- 28752999
TI  - Polycationic Polymer-Regulated Assembling of 2D MOF Nanosheets for High
      Performance Nanofiltration.
AB  - Herein, a two-dimensional metal-organic framework (2D MOF) made of iron porphyrin
      complex (TCP(Fe)) interconnected with divalent metal ion (M = Zn, Co, and Cu) is
      used to construct a selective layer, which is explored as an ultrafast and energy
      saving nanofiltration (NF) membrane for removing organic dyes from water. Among
      the layered 2D M-TCP(Fe) membranes, Zn-TCP(Fe) membranes display the highest
      water permeance, which is 3 times higher than graphene-based membranes with
      similar rejection. To further improve the separation performances, we utilize
      polycations to anchor the periphery carboxylic groups of nanosheets, regulating
      the assembly of 2D Zn-TCP(Fe) nanosheets to produce a new class of crack-free
      selective layer possessing ultrathin and highly ordered nanochannels for
      efficient NF. Benefiting from these structural features, our polycation-regulated
      2D Zn-TCP(Fe) membranes could offer ultrahigh permeance of 4243 L m-2 h-1 bar-1
      (2-fold higher than its pristine) and excellent rejection rates (over 90%) for
      organic dye with size larger than 0.8 * 1.1 nm. This permeance value is about 2
      orders of magnitude higher than the commercial polymeric NF membrane.
      Additionally, the membranes demonstrate 20-40% salt rejection.

PMID- 28753000
TI  - An Easy to Manufacture Micro Gas Preconcentrator for Chemical Sensing
      Applications.
AB  - We have developed a simple-to-manufacture microfabricated gas preconcentrator for
      MEMS-based chemical sensing applications. Cavities and microfluidic channels were
      created using a wet etch process with hydrofluoric acid, portions of which can be
      performed outside of a cleanroom, instead of the more common deep reactive ion
      etch process. The integrated heater and resistance temperature detectors (RTDs)
      were created with a photolithography-free technique enabled by laser etching.
      With only 28 V DC (0.1 A), a maximum heating rate of 17.6  degrees C/s was
      observed. Adsorption and desorption flow parameters were optimized to be 90 SCCM
      and 25 SCCM, respectively, for a multicomponent gas mixture. Under testing
      conditions using Tenax TA sorbent, the device was capable of measuring analytes
      down to 22 ppb with only a 2 min sample loading time using a gas chromatograph
      with a flame ionization detector. Two separate devices were compared by measuring
      the same chemical mixture; both devices yielded similar peak areas and widths
      (fwhm: 0.032-0.033 min), suggesting reproducibility between devices.

PMID- 28753001
TI  - Stabilization of Lithium Transition Metal Silicates in the Olivine Structure.
AB  - While olivine LiFePO4 shows amongst the best electrochemical properties of Li-ion
      positive electrodes with respect to rate behavior owing to facile Li+ migration
      pathways in the framework, replacing the [PO4]3- polyanion with a silicate
      [SiO4]4- moiety in olivine is desirable. This could allow additional alkali
      content and hence electron transfer, and increase the capacity. Herein we explore
      the possibility of a strategy toward new cathode materials and demonstrate the
      first stabilization of a lithium transition metal silicate (as a pure silicate)
      in the olivine structure type. Using LiInSiO4 and LiScSiO4 as the parent
      materials, transition metal (Mn, Fe, Co) substitutions on the In/Sc site were
      investigated by computational modeling via atomic scale simulation. Transition
      metal substitution was found to be only favorable for Co, a finding confirmed by
      the successful solid state synthesis of olivine LixInyCo2-x-ySiO4. Stabilization
      of the structure was achieved by entropy provided by cation disorder.

PMID- 28753002
TI  - Efficient Formation of Light-Absorbing Polymeric Nanoparticles from the Reaction
      of Soluble Fe(III) with C4 and C6 Dicarboxylic Acids.
AB  - The role of transition metals in the formation and aging of secondary organic
      aerosol (SOA) from aliphatic and aromatic precursors in heterogeneous/multiphase
      reactions is not well understood. The reactivity of soluble Fe(III) toward known
      benzene photooxidation products that include fumaric (trans-butenedioic) and
      muconic (trans,trans-2,4-hexadienedioic) acids was investigated. Efficient
      formation of brightly colored nanoparticles was observed that are mostly rod- or
      irregular-shaped depending on the structure of the organic precursor. The
      particles were characterized for their optical properties, growth rate, elemental
      composition, iron content, and oxidation state. Results indicate that these
      particles have mass absorption coefficients on the same order as black carbon and
      larger than that of biomass burning aerosols. The particles are also amorphous in
      nature and consist of polymeric chains of Fe centers complexed to carboxylate
      groups. The oxidation state of Fe was found to be in between Fe(III) and Fe(II)
      in standard compounds. The organic reactant to iron molar ratio and pH were found
      to affect the particle growth rate. Control experiments using maleic acid (cis
      butenedioic acid) and succinic acid (butanedioic acid) produced no particles. The
      formation of particles reported herein could account for new pathways that lead
      to SOA and brown carbon formation mediated by transition metals. In addition, the
      multiple chemically active components in these particles (iron, organics, and
      acidic groups) may have an effect on their chemical reactivity (enhanced uptake
      of trace gases, catalysis, and production of reactive oxygen species) and their
      likely poor cloud/ice nucleation properties.

PMID- 28753003
TI  - Site of Tagging Influences the Ochratoxin Recognition by Peptide NFO4: A
      Molecular Dynamics Study.
AB  - Molecular recognition by synthetic peptides is growing in importance in the
      design of biosensing elements used in the detection and monitoring of a wide
      variety of hapten bioanlaytes. Conferring specificity via bioimmobilization and
      subsequent recovery and purification of such sensing elements are aided by the
      use of affinity tags. However, the tag and its site of placement can potentially
      compromise the hapten recognition capabilities of the peptide, necessitating a
      detailed experimental characterization and optimization of the tagged molecular
      recognition entity. The objective of this study was to assess the impact of site
      specific tags on a native peptide's fold and hapten recognition capabilities
      using an advanced molecular dynamics (MD) simulation approach involving bias
      exchange metadynamics and Markov State Models. The in-solution binding
      preferences of affinity tagged NFO4 (VYMNRKYYKCCK) to chlorinated (OTA) and non
      chlorinated (OTB) analogues of ochratoxin were evaluated by appending hexa
      histidine tags (6* His-tag) to the peptide's N-terminus (NterNFO4) or C-terminus
      (CterNFO4), respectively. The untagged NFO4 (NFO4), previously shown to bind with
      high affinity and selectivity to OTA, served as the control. Results indicate
      that the addition of site-specific 6* His-tags altered the peptide's native fold
      and the ochratoxin binding mechanism, with the influence of site-specific
      affinity tags being most evident on the peptide's interaction with OTA. The tags
      at the N-terminus of NFO4 preserved the native fold and actively contributed to
      the nonbonded interactions with OTA. In contrast, the tags at the C-terminus of
      NFO4 altered the native fold and were agnostic in its nonbonded interactions with
      OTA. The tags also increased the penalty associated with solvating the peptide
      OTA complex. Interestingly, the tags did not significantly influence the
      nonbonded interactions or the penalty associated with solvating the peptide-OTB
      complex. Overall, the combined contributions of nonbonded interaction and
      solvation penalty were responsible for the retention of the native hapten
      recognition capabilities in NterNFO4 and compromised native recognition
      capabilities in CterNFO4. Advanced MD approaches can thus provide structural and
      energetic insights critical to evaluate the impact of site-specific tags and may
      aid in the selection and optimization of the binding preferences of a specific
      biosensing element.

PMID- 28753004
TI  - Palladium-Catalyzed Negishi Coupling of alpha-CF3 Oxiranyl Zincate: Access to
      Chiral CF3-Substituted Benzylic Tertiary Alcohols.
AB  - We report a Pd-catalyzed stereospecific alpha-arylation of optically pure 2,3
      epoxy-1,1,1-trifluoropropane (TFPO). This method allows for the direct and
      reliable preparation of optically pure 2-CF3-2-(hetero)aryloxiranes, which are
      precursors to many CF3-substituted tertiary alcohols. The use of continuous-flow
      methods has allowed the deprotonation of TFPO and subsequent zincation at higher
      temperature compared to that under traditional batch conditions.

PMID- 28753005
TI  - Polyethylenimine-Functionalized Corn Bract, an Agricultural Waste Material, for
      Efficient Removal and Recovery of Cr(VI) from Aqueous Solution.
AB  - In this study, polyethylenimine-functionalized corn bract (PEI-CB) was first used
      to remove aqueous Cr(VI) via the "waste control by waste" concept. The results
      indicated that PEI-CB had an excellent performance for Cr(VI) removal and the
      maximum removal capacity was 438 mg/g. The adsorption of Cr(VI) was fitted to the
      Langmuir model, and kinetics of uptake could be described by a pseudo-second
      order rate model well. Amine was proven to be the active center for Cr(VI)
      adsorption and partial reduction to Cr(III), while removal efficiency was
      enhanced at a lower pH value and higher temperature. Besides, nanosized Cr2O3
      with a high purity was obtained by simple calcination of a Cr(VI)-laden
      adsorbent. Hence, this study provided a novel strategy for Cr(VI) wastewater
      remediation and pure Cr2O3 recovery. Prepared PEI-CB was then a promising
      alternative of low cost for replacement of the current expensive absorbent of
      removing Cr(VI) from wastewater from the view of sustainability.

PMID- 28753006
TI  - Ultrafast Excited-State Deactivation of the Bacterial Pigment Violacein.
AB  - The photophysical properties of the natural pigment violacein extracted from an
      Antarctic organism adapted to high exposure levels of UV radiation were measured
      in a combined steady-state and time-resolved spectroscopic study for the first
      time. In the low-viscosity solvents methanol and acetone, violacein exhibits low
      fluorescence quantum yields on the order of 10-4, and femtosecond transient
      absorption measurements reveal excited-state lifetimes of 3.2 +/- 0.2 and 4.5 +/-
      0.2 picoseconds in methanol and acetone, respectively. As solvent viscosity is
      increased, both the fluorescence quantum yield and excited-state lifetime of this
      intensely colored pigment increase dramatically and stimulated emission decays 30
      fold more slowly in glycerol than in methanol at room temperature. Excited-state
      deactivation is suggested to occur via a molecular-rotor mechanism in which
      torsion about an interring bond leads to a conical intersection with the ground
      state.

PMID- 28753009
TI  - Origins of Protons in C-H Bond Insertion Products of Phenols: Proton-Self
      Sufficient Function via Water Molecules.
AB  - Water molecules can serve as proton shuttles for proton transfer in the C-H bond
      insertion reactions catalyzed by transition metal complexes. Recently, the
      control experiments performed for C-H bond insertion of phenol and anisol by gold
      carbenes show that large discrepancy exists in the yields of hydrogenated and
      deuterated products. Thus, we conducted a detailed theoretical analysis on the
      function of water molecules in the C-H bond insertion reactions. The comparison
      of calculated results and control experiments indicates that the solution water
      molecules play a crucial role of proton shuttle in C-H bond insertion. In
      particular, it was found that the hydroxyl groups in phenols were capable of
      donating protons via water shuttles for the production of C-H products, which had
      a substantial influence on the yields of inserted products. The hydroxyl groups
      instead of C-H bonds in phenols function like "proton reservoirs" in the C-H bond
      insertion, which we call the "proton self-sufficient" (PSS) function of phenol.
      The PSS function of phenol indicates that the substrates with and without proton
      reservoirs will lead to different C-H bond insertion products.

PMID- 28753007
TI  - Site-Selective Copper-Catalyzed Amination and Azidation of Arenes and
      Heteroarenes via Deprotonative Zincation.
AB  - Arene amination is achieved by site-selective C-H zincation followed by copper
      catalyzed coupling with O-benzoylhydroxylamines under mild conditions. Key to
      this success is ortho-zincation mediated by lithium amidodiethylzincate base that
      is effective for a wide range of arenes, including nonactivated arenes bearing
      simple functionalities such as fluoride, chloride, ester, amide, ether, nitrile,
      and trifluoromethyl groups as well as heteroarenes including indole, thiophene,
      pyridine, and isoquinoline. An analogous C-H azidation is also accomplished using
      azidoiodinane for direct introduction of a useful azide group onto a broad scope
      of arenes and heteroarenes. These new transformations offer rapid access to
      valuable and diverse chemical space of aminoarenes. Their broad applications in
      organic synthesis and drug discovery are demonstrated in the synthesis of novel
      analogues of natural product (-)-nicotine and antidepressant sertraline by late
      stage amination and azidation reactions.

PMID- 28753008
TI  - Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis
      Reaction.
AB  - Iron(III)-catalyzed carbonyl-olefin ring-closing metathesis represents a new
      approach toward the assembly of molecules traditionally generated by olefin
      olefin metathesis or olefination. Herein, we report detailed synthetic,
      spectroscopic, kinetic, and computational studies to determine the mechanistic
      features imparted by iron(III), substrate, and temperature to the catalytic
      cycle. These data are consistent with an iron(III)-mediated asynchronous,
      concerted [2+2]-cycloaddition to form an intermediate oxetane as the turnover
      limiting step. Fragmentation of the oxetane via Lewis acid-activation results in
      the formation of five- and six-membered unsaturated carbocycles.

PMID- 28753010
TI  - Selective Hydrogen Adsorption in Graphene Rotated Bilayers.
AB  - The absorption energy of atomic hydrogen at rotated graphene bilayers is studied
      using ab initio methods based on the density functional theory including van der
      Waals interactions. We find that, due to the surface corrugation induced by the
      underneath rotated layer and the perturbation of the electronic density of states
      near the Fermi energy, the atoms with an almost AA stacking are the preferential
      ones for hydrogen chemisorption. The adsorption energy difference between
      different atoms can be as large as 80 meV. In addition, we find that, due to the
      logarithmic van Hove singularities in the electronic density of states at
      energies close to the Dirac point, the adsorption energy of either electron or
      hole doped samples is substantially increased. We also find that the adsorption
      energy increases with the decrease of the rotated angle between the layers.
      Finally, the large zero point energy of the C-H bond (~0.3 eV) suggests
      adsorption and desorption of atomic hydrogen and deuterium should behave
      differently.

PMID- 28753011
TI  - Development of Biligands Magnesium Catalysis in Asymmetric Conjugate Reactions of
      C3-Pyrrolyl-Oxindoles.
AB  - A magnesium catalyzed asymmetric conjugate reaction of C3-pyrrolyl-oxindoles with
      terminal alkynones is presented. The current asymmetric conjugate reaction relies
      on the development of novel combinational magnesium catalysis involving two
      chiral ligands. The current protocol proceeds smoothly and gives the
      corresponding enantioenriched 3,3-disubstituted oxindole skeletons with good
      enantioselectivities. Furthermore, the conjugate adducts could be transferred to
      spiro oxindole structures containing an eight-membered ring in high ee values.

PMID- 28753012
TI  - Identification of Urinary Food Intake Biomarkers for Milk, Cheese, and Soy-Based
      Drink by Untargeted GC-MS and NMR in Healthy Humans.
AB  - The measurement of food intake biomarkers (FIBs) in biofluids represents an
      objective tool for dietary assessment. FIBs of milk and cheese still need more
      investigation due to the absence of candidate markers. Thus, an acute
      intervention study has been performed to sensitively and specifically identify
      candidate FIBs. Eleven healthy male and female volunteers participated in the
      randomized, controlled crossover study that tested a single intake of milk and
      cheese as test products, and soy-based drink as a control. Urine samples were
      collected at baseline and up to 24 h at distinct time intervals (0-1, 1-2, 2-4, 4
      6, 6-12, and 12-24 h) and were analyzed using an untargeted multiplatform
      approach (GC-MS and 1H NMR). Lactose, galactose, and galactonate were identified
      exclusively after milk intake while for other metabolites (allantoin, hippurate,
      galactitol, and galactono-1,5-lactone) a significant increase has been observed.
      Urinary 3-phenyllactic acid was the only compound specifically reflecting cheese
      intake although alanine, proline, and pyroglutamic acid were found at
      significantly higher levels after cheese consumption. In addition, several novel
      candidate markers for soy drink were identified, such as pinitol and
      trigonelline. Together, these candidate FIBs of dairy intake could serve as a
      basis for future validation studies under free-living conditions.

PMID- 28753013
TI  - Protein-Protein Interaction Probed by Label-free Second Harmonic Light
      Scattering: Hemoglobin Adsorption on Spectrin Surface as a Case Study.
AB  - In this article, we have studied the binding of different naturally occurring
      hemoglobin (Hb) variants on erythrocyte skeletal protein, spectrin surface using
      the label free nondestructive second harmonic light scattering (SHLS) technique
      in aqueous buffer. Hemoglobin variants like sickle hemoglobin (HbS) and
      hemoglobin E (HbE) were chosen as they associate with sickle cell disease and
      HbEbeta-thalassemia, respectively, and their interaction with spectrin is
      compared with normal adult hemoglobin (HbA). The concentration dependent change
      in the second harmonic light intensity from nanomolar spectrin solution has been
      measured after addition of small aliquots of hemoglobins. From the second
      harmonic titration data, the binding constant is calculated using a modified
      Langmuir adsorption model of hemoglobin binding to the spectrin surface.
      Interestingly, it is found that the binding constant for HbE (13.8 * 108 M-1) is
      1 order of magnitude higher than that of HbS (1.6 * 108 M-1) or HbA (2.1 * 108 M
      1) which indicates higher affinity of HbE for spectrin compared to HbA and HbS.
      The number of the Hb molecules bound to the spectrin surface was estimated to be
      of the order of hundred's which is determined for the first time.

PMID- 28753014
TI  - X-ray Absorption Spectroscopy of Aliphatic Organic Sulfides.
AB  - Organic sulfides, sometimes called thioethers, are important in a variety of
      materials with diverse roles in biology and the environment. They also contribute
      a significant proportion of the sulfur in fossil fuels. We have studied a range
      of aliphatic sulfides using a combination of sulfur K-edge X-ray absorption
      spectroscopy and density functional theory calculations. We show that the sulfur
      K-edge near-edge X-ray absorption spectra of aliphatic organic sulfides comprise
      two intense transitions in the near-edge spectrum, which can be assigned as 1s ->
      (S-C)sigma* and 1s -> (S-C)pi* transitions. These transitions are found to change
      in a systematic manner in sterically hindered sulfides composed of four-, five-
      and six-membered rings. Both the 1s -> (S-C)sigma* and 1s -> (S-C)pi* transitions
      are sensitive to the presence of strain in the C-S-C angle, shifting to lower
      values with more strained ring systems. Steric effects can give obtuse C-S-C
      angles, which are predicted to cause the two transitions to converge to the same
      energy and even cross over at very obtuse angles.

PMID- 28753015
TI  - Synthesis of 1,2-Bis(trifluoromethylthio)arenes via Aryne Intermediates.
AB  - A general method for synthesis of 1,2-bis-trifluoromethylthioarenes has been
      developed. Arynes generated from silyl aryl triflates or halides react with
      bis(trifluoromethyl)disulfide to afford 1,2-bis-trifluoromethylthioarenes. Aryl,
      alkyl, ester, halide, and methoxy functionalities are compatible with reaction
      conditions. Use of bis(perfluoroaryl)disulfides gave moderate yields of aryne
      disulfenylation or cyclization to fluorinated dibenzothiophenes.

PMID- 28753016
TI  - High-Throughput Metabolomics for Discovering Potential Metabolite Biomarkers and
      Metabolic Mechanism from the APPswe/PS1dE9 Transgenic Model of Alzheimer's
      Disease.
AB  - Alzheimer's disease (AD), a neurodegenerative disorder, is the major form of
      dementia. As AD is an irreversible disease, it is necessary to focus on earlier
      intervention. However, the potential biomarkers of preclinical AD are still not
      clear. In this study, urinary metabolomics based on ultra-high-performance liquid
      chromatography coupled with quadruple time-of-flight mass spectrometry was
      performed for delineating the metabolic changes and potential early biomarkers in
      APPswe/PS1dE9 (APP/PS1) transgenic mice. A total of 24 differentially regulated
      metabolites were identified when comparing transgenic mice to wild-type mice
      using multivariate statistical analysis. Among them, 10 metabolites were
      significantly upregulated and 14 metabolites were downregulated. On the basis of
      these potential biomarkers, metabolic pathway analysis found that pentose and
      glucuronate interconversions, glyoxylate and dicarboxylate metabolism, starch and
      sucrose metabolism, the citrate cycle, tryptophan metabolism, and arginine and
      proline metabolism were disturbed in APP/PS1 mice. Our study revealed that levels
      of endogenous metabolites in the urine of APP/PS1 mice changed prior to the
      emergence of learning and cognitive impairment, which may be associated with
      abnormal nitric oxide production pathways and metabolic disorders of
      monoaminergic neurotransmitters. In conclusion, this study showed that
      metabolomics provides an early indicator of disease occurrence for AD.

PMID- 28753017
TI  - Acidity-Triggered Ligand-Presenting Nanoparticles To Overcome Sequential Drug
      Delivery Barriers to Tumors.
AB  - The success of cancer chemotherapy is impeded by poor drug delivery efficiency
      due to the existence of a series of pathophysiological barriers in the tumor. In
      this study, we reported a tumor acidity-triggered ligand-presenting (ATLP)
      nanoparticle for cancer therapy. The ATLP nanoparticles were composed of an acid
      responsive diblock copolymer as a sheddable matrix and an iRGD-modified polymeric
      prodrug of doxorubicin (iPDOX) as an amphiphilic core. A PEG corona of the
      polymer matrix protected the iRGD ligand from serum degradation and nonspecific
      interactions with the normal tissues while circulating in the blood. The ATLP
      nanoparticles specifically accumulated at the tumor site through the enhanced
      permeability and retention (EPR) effect, followed by acid-triggered dissociation
      of the polymer matrix within the tumoral acidic microenvironment (pH ~ 6.8) and
      subsequently exposing the iRGD ligand for facilitating tumor penetration and
      cellular uptake of the PDOX prodrug. Additionally, the acid-triggered
      dissociation of the polymer matrix induced a 4.5-fold increase of the fluorescent
      signal for monitoring nanoparticle activation in vivo. Upon near-infrared (NIR)
      laser irradiation, activation of Ce6-induced significant reactive oxygen species
      (ROS) generation, promoted drug diffusion inside the tumor mass and circumvented
      the acquired drug resistance by altering the gene expression profile of the tumor
      cells. The ATLP strategy might provide a novel insight for cancer nanomedicine.

PMID- 28753018
TI  - Temperature-Induced Large Broadening and Blue Shift in the Electronic Band
      Structure and Optical Absorption of Methylammonium Lead Iodide Perovskite.
AB  - The power conversion efficiency of hybrid halide perovskite solar cells is
      profoundly influenced by the operating temperature. Here we investigate the
      temperature influence on the electronic band structure and optical absorption of
      cubic CH3NH3PbI3 from first-principles by accounting for both the electron-phonon
      interaction and thermal expansion. Within the framework of density functional
      perturbation theory, the electron-phonon coupling induces slightly enlarged band
      gap and strongly broadened electronic relaxation time as temperature increases.
      The large broadening effect is mainly due to the presence of cation organic
      atoms. Consequently, the temperature-dependent absorption peak exhibits blue
      shift position, decreased amplitude, and broadened width. This work uncovers the
      atomistic origin of temperature influence on the optical absorption of cubic
      CH3NH3PbI3 and can provide guidance to design high-performance hybrid halide
      perovskite solar cells at different operating temperatures.

PMID- 28753019
TI  - Nickel Catalyzed Regio-, Diastereo-, and Enantioselective Cross-Coupling of 3,4
      Epoxyalcohol with Aryl Iodides.
AB  - The first catalytic, regioselective cross-coupling of 3,4-epoxyalcohol with aryl
      iodides is reported. The combination of NiCl2.DME and a newly developed C2
      symmetric oxazoline ligand plays a key role in selective ring opening of several
      3,4-epoxy alcohols at the C4 position. This general protocol furnishes a new type
      of enantioenriched 4,4-diaryl alkane which also incorporates an additional 1,3
      diol that can be easily transformed to a variety of functional groups. The
      products are formed with excellent regioselectivity (>99:1), diastereoselectivity
      (up to 99:1), and enantiopurity (up to >99.9% ee).

PMID- 28753020
TI  - Palladium-Catalyzed Si-C Bond Formation toward Sila-Annulated Perylene Diimides.
AB  - The first example of sila-annulation onto the perylene diimide core that allows
      the effective and practical synthesis of both sila- and disilaperylene diimides
      (Si-PDIs and 2Si-PDIs) in one pot through palladium-catalyzed Si-C bond formation
      is presented. The corresponding sila-annulated perylene diimides demonstrated
      exceptional optical properties with noteworthy bathochromic shifts and excellent
      fluorescence quantum yields. Single crystal analysis revealed almost planar
      molecular structures and distinct packing arrangements with intense pi-pi
      interactions. Their single crystal OFET devices showed good electron mobilities
      of up to 0.3 cm2 V-1 s-1 under a nitrogen atmosphere.

PMID- 28753021
TI  - Oxygen-18 Isotopic Studies of HOOO and DOOO.
AB  - Owing to questions that still persist regarding the length of the O-H and central
      O-O bond, and large-amplitude torsional motion of trans hydridotrioxygen HOOO, a
      weakly bound complex between OH and O2, new 18O isotopic measurements of HOOO and
      DOOO were undertaken using Fourier transform microwave and microwave-millimeter
      wave double resonance techniques. Rotational lines from three new 18O species of
      DOOO (D18OOO, DO18O18O, and D18O18O18O) were detected, along with the two singly
      substituted 18O isotopic species of HOOO (HO18OO and HOO18O) that were not
      measured in the previous isotopic investigation. From a least-squares fit,
      spectroscopic constants, including the three rotational constants, were precisely
      determined for all five species. The inertial defect of DOOO and its 18O species
      is uniformly negative: of order -0.04 amu A2, regardless of the number or
      location of the 18O atoms, in contrast to that found for HOOO or its 18O isotopic
      species. A reanalysis of the molecular structure was performed using either
      normal HOOO and its four singly substituted isotopic species, the new DOOO data,
      or all the isotopic species (10 in total). The differences between the purely
      experimental (r0) structures are generally quite small, of order +/-0.01 A for
      the bond lengths and +/-1 degrees  for the bond angle. The length of the O-H bond
      remains unrealistically short compared to free OH, and the central O-O bond
      length is consistently very close to 1.68 A. On the basis of the effective O-H
      bond length derived from the experimental structure, the average displacement of
      the large amplitude torsional motion from planarity is estimated to be ~22
      degrees .

PMID- 28753022
TI  - Structural Control of Kinetics for Macrocycle Threading by Fluorescent Squaraine
      Dye in Water.
AB  - While the general concept of steric speed bumps has been demonstrated in rotaxane
      shuttles and macrocycle threading systems, the sensitivity of speed bump effects
      has not been evaluated as a function of structural geometry. Values of Ka and kon
      for macrocycle threading in water are reported for a series of homologous
      squaraine dyes with different substituents (speed bumps) on the flanking chains
      and two macrocycles with different cavity sizes. Sensitivity to a steric speed
      bump effect was found to depend on (a) structural location, being lowest when the
      speed bump was near the end of a flanking chain, and (b) macrocycle cavity size,
      which was enhanced when the cavity was constricted. This new insight is broadly
      applicable to many types of molecular threading systems.

PMID- 28753023
TI  - Transparent and Highly Responsive Phototransistors Based on a Solution-Processed,
      Nanometers-Thick Active Layer, Embedding a High-Mobility Electron-Transporting
      Polymer and a Hole-Trapping Molecule.
AB  - Organic materials are suitable for light sensing devices showing unique features
      such as low cost, large area, and flexibility. Moreover, transparent
      photodetectors are interesting for smart interfaces, windows, and display
      integrated electronics. The ease of depositing ultrathin organic films with
      simple techniques enables low light absorbing active layers, resulting in the
      realization of transparent devices. Here, we demonstrate a strategy to obtain
      high efficiency organic photodetectors and phototransistors based on transparent
      active layers with a visible transmittance higher than 90%. The photoactive layer
      is composed of two phases, each a few nanometers thick. First, an acceptor
      polymer, which is a good electron-transporting material, on top of which a small
      molecule donor material is deposited, forming noncontinuous domains. The small
      molecule phase acts as a trap for holes, thus inducing a high photoconductive
      gain, resulting in a high photoresponsivity. The organic transparent detectors
      proposed here can reach very high external quantum efficiency and responsivity
      values, which in the case of the phototransistors can be as high as ~74000% and
      340 A W-1 at 570 nm respectively, despite an absorber total thickness below 10
      nm. Moreover, frequency dependent 2D photocurrent mapping allows discrimination
      between the contribution of a fast but inefficient and highly spatially localized
      photoinduced injection mechanism at the electrodes, and the onset of a slower and
      spatially extended photoconductive process, leading to high responsivity.

PMID- 28753024
TI  - Thiocarbonyl Ylide Chemistry Enables a Concise Synthesis of (+/-)-Hippolachnin A.
AB  - Hippolachnin A (1) is an antifungal polyketide that bristles with ethyl groups
      mounted onto a caged heterotricyclic core. It has shown potent activity against
      Cryptococcus neoformans, a yeast that can affect immunocompromised patients as an
      opportunistic pathogen. Herein we describe a concise, diversifiable, and scalable
      synthesis of (+/-)-hippolachnin A (1). It features a powerful photochemical
      opening step, a diastereoselective addition of an ethyl cuprate and an unusual
      strategy to install two additional ethyl groups that makes use of a thiocarbonyl
      ylide generated in situ.

PMID- 28753025
TI  - Identification of Droplet-Flow-Induced Electric Energy on Electrolyte-Insulator
      Semiconductor Structure.
AB  - Recently, various energy transducers driven by the relative motion of solids and
      liquids have been demonstrated. However, in relation to the energy transducer, a
      proper understanding of the dynamic behavior of ions remains unclear. Moreover,
      the energy density is low for practical usage mainly due to structural
      limitations, a lack of material development stemming from the currently poor
      understanding of the mechanisms, and the intermittently generated electricity
      given the characteristics of the water motion (pulsed signals). Here, we verify a
      hypothesis pertaining to the ion dynamics which govern the operation mechanism of
      the transducer. In addition, we demonstrate enhanced energy transducer to convert
      the mechanical energy of flowing water droplets into continuous electrical energy
      using an electrolyte-insulator-semiconductor structure as a device structure. The
      output power per droplet mass and the ratio of generated electric energy to the
      kinetic energy of water drops are 0.149v2 mW.g-1.m-2.s2 and 29.8%, respectively,
      where v is the speed of the water droplet.

PMID- 28753026
TI  - Tropospheric Aqueous-Phase Oxidation of Isoprene-Derived Dihydroxycarbonyl
      Compounds.
AB  - The dihydroxycarbonyls 3,4-dihydroxy-2-butanone (DHBO) and 2,3-dihydroxy-2
      methylpropanal (DHMP) formed from isoprene oxidation products in the atmospheric
      gas phase under low-NO conditions can be expected to form aqSOA in the
      tropospheric aqueous phase because of their solubility. In the present study,
      DHBO and DHMP were investigated concerning their radical-driven aqueous-phase
      oxidation reaction kinetics. For DHBO and DHMP the following rate constants at
      298 K are reported: k(OH + DHBO) = (1.0 +/- 0.1) * 109 L mol-1 s-1, k(NO3 + DHBO)
      = (2.6 +/- 1.6) * 106 L mol-1 s-1, k(SO4-+ DHBO) = (2.3 +/- 0.2) * 107 L mol-1 s
      1, k(OH + DHMP) = (1.2 +/- 0.1) * 109 L mol-1 s-1, k (NO3 + DHMP) = (7.9 +/- 0.7)
      * 106 L mol-1 s-1, k(SO4- + DHMP) = (3.3 +/- 0.2) * 107 L mol-1 s-1, together
      with their respective temperature dependences. The product studies of both DHBO
      and DHMP revealed hydroxydicarbonyls, short chain carbonyls, and carboxylic
      acids, such as hydroxyacetone, methylglyoxal, and lactic and pyruvic acid as
      oxidation products with single yields up to 25%. The achieved carbon balance was
      75% for DHBO and 67% for DHMP. An aqueous-phase oxidation scheme for both DHBO
      and DHMP was developed on the basis of the experimental findings to show their
      potential to contribute to the aqSOA formation. It can be expected that the main
      contribution to aqSOA occurs via acid formation while other short-chain oxidation
      products are expected to back-partition into the gas phase to undergo further
      oxidation there.

PMID- 28753027
TI  - 1H NMR Metabolic Profiling of Earthworm (Eisenia fetida) Coelomic Fluid,
      Coelomocytes, and Tissue: Identification of a New Metabolite-Malylglutamate.
AB  - Earthworm metabolism is recognized as a useful tool for monitoring environmental
      insults and measuring ecotoxicity, yet extensive earthworm metabolic profiling
      using 1H nuclear magnetic resonance (NMR) spectroscopy has been limited in scope.
      This study aims to expand the embedded metabolic material in earthworm coelomic
      fluid, coelomocytes, and tissue to aid systems toxicology research. Fifty-nine
      metabolites within Eisenia fetida were identified, with 47 detected in coelomic
      fluid, 41 in coelomocytes, and 54 in whole-worm samples and tissue extracts. The
      newly detected but known metabolites 2-aminobutyrate, nicotinurate,
      Ndelta,Ndelta,Ndelta-trimethylornithine, and trigonelline are reported along with
      a novel compound, malylglutamate, elucidated using 2D NMR and high-resolution
      MS/MS. We postulate that malylglutamate acts as a glutamate/malate store,
      chelator, and anionic osmolyte and helps to provide electrolyte balance.

PMID- 28753028
TI  - General Linker Diversification Approach to Bivalent Ligand Assembly: Generation
      of an Array of Ligands for the Cation-Independent Mannose 6-Phosphate Receptor.
AB  - A generalized strategy is presented for the rapid assembly of a set of bivalent
      ligands with a variety of linking functionalities from a common monomer. Herein,
      an array of phosphatase-inert mannose-6-phosphonate-presenting ligands for the
      cation-independent-mannose 6-phosphate receptor (CI-MPR) is constructed. Receptor
      binding affinity varies with linking functionality-the simple amide and 1,5
      triazole(tetrazole) being preferred over the 1,4-triazole. This approach is
      expected to find application across chemical biology, particularly in
      glycoscience, wherein multivalency often governs molecular recognition.

PMID- 28753029
TI  - Synthesis of Naphthyridine Carbamate Dimer (NCD) Derivatives Modified with
      Alkanethiol and Binding Properties of G-G Mismatch DNA.
AB  - A series of new DNA binding molecules NCD-Cn-SH (n = 3, 4, 5, and 6) is reported,
      which possesses the NCD (naphthyridine carbamate dimer) domain selectively
      binding to the G-G mismatch in the 5'-CGG-3'/5'-CGG-3' sequence and a thiol
      moiety, which undergoes spontaneous dimerization to (NCD-Cn-S)2 upon oxidation
      under aerobic conditions. The S-S dimer (NCD-Cn-S)2 produced the 1:1 binding
      complex with improved thermal stability. The dimer binding to the CGG/CGG DNA
      showed higher positive cooperativity than the binding of monomer and previously
      synthesized NCTn derivative. The dimerization of NCD-Cn-SH was selectively
      accelerated on the CGG repeat DNA but not on the CAG repeat DNA.

PMID- 28753030
TI  - Efficacy of Combined Treatment with Acupuncture and Bee Venom Acupuncture as an
      Adjunctive Treatment for Parkinson's Disease.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of acupuncture and
      bee venom acupuncture (BVA) for idiopathic Parkinson's disease (IPD) through a
      sham-controlled trial. We also investigated whether there is a sustained
      therapeutic effect by completing follow-up assessments after treatment
      completion. DESIGN: A single center, double-blind, three-armed randomized
      controlled trial. SETTINGS/LOCATION: This study was performed at a university
      hospital in Seoul, Republic of Korea. SUBJECTS: Seventy-three (73) patients with
      IPD were the subjects. They were randomly assigned to the active treatment group,
      sham treatment group, or conventional treatment group. INTERVENTIONS: The active
      treatment group received acupuncture and BVA and the sham group received sham
      acupuncture and normal saline injections, twice a week for 12 weeks. The
      conventional treatment group maintained anti-parkinsonian drugs without
      additional intervention. OUTCOME MEASURES: The Unified Parkinson's Disease Rating
      Scale (UPDRS) part II and part III score, postural instability and gait
      disturbance (PIGD) score, gait speed and number, Parkinson's Disease Quality of
      Life Questionnaire, Beck Depression Inventory, and postural stability at baseline
      and at 12, 16, and 20 weeks. RESULTS: Sixty-three (63) patients provided a
      complete data of assessments, including a final follow-up. After 12 weeks of
      treatment, a significant difference was observed between the active treatment
      group and the conventional treatment group. After the end of the treatment, the
      treatment effects were maintained significantly in the active treatment group
      only. CONCLUSIONS: It is suggested that the combined treatment of acupuncture and
      BVA might be safe and useful adjunctive treatment for patients with IPD.

PMID- 28753031
TI  - Computer-Aided Detection of Colorectal Polyps at CT Colonography: Prospective
      Clinical Performance and Third-Party Reimbursement.
AB  - OBJECTIVE: We assessed the initial clinical performance and third-party
      reimbursement rates of supplementary computer-aided detection (CAD) at CT
      colonography (CTC) for detecting colorectal polyps 6 mm or larger in routine
      clinical practice. MATERIALS AND METHODS: We retrospectively assessed the
      prospective clinical performance of a U.S. Food and Drug Administration-approved
      CAD system in second-reader mode in 347 consecutive adults (mean age, 57.6 years;
      205 women, 142 men) undergoing CTC evaluation over a 5-month period. The
      reference standard consisted of the prospective interpretation by experienced CTC
      radiologists combined with subsequent optical colonoscopy (OC), if performed. We
      also assessed third-party reimbursement for CAD for studies performed over an 18
      month period. RESULTS: In all, 69 patients (mean [+/- SD] age, 59.0 +/- 7.7
      years; 32 men, 37 women) had 129 polyps >= 6 mm. Per-patient CAD sensitivity was
      91.3% (63 of 69). Per-polyp CAD-alone sensitivity was 88.4% (114 of 129),
      including 88.3% (83 of 94) for 6- to 9-mm polyps and 88.6% (31 of 35) for polyps
      10 mm or larger. On retrospective review, three additional polyps 6 mm or larger
      were seen at OC and marked by CAD but dismissed as CAD false-positives at CTC.
      The mean number of false-positive CAD marks was 4.4 +/- 3.1 per series. Of 1225
      CTC cases reviewed for reimbursement, 31.0% of the total charges for CAD
      interpretation had been recovered from a variety of third-party payers.
      CONCLUSION: In our routine clinical practice, CAD showed good sensitivity for
      detecting colorectal polyps 6 mm or larger, with an acceptable number of false
      positive marks. Importantly, CAD is already being reimbursed by some third-party
      payers in our clinical CTC practice.

PMID- 28753032
TI  - Discomfort associated with Invisalign and traditional brackets: A randomized,
      prospective trial.
AB  - OBJECTIVE: To evaluate differences in discomfort levels between patients treated
      with aligners and traditional fixed orthodontic appliances. MATERIALS AND
      METHODS: This blinded, prospective, randomized equivalence two-arm parallel trial
      allocated 41 adult Class I nonextraction patients to either traditional fixed
      appliance (6 males and 12 females) or aligner (11 males and 12 females)
      treatment. Patients completed daily discomfort diaries following their initial
      treatment appointment, after 1 month and after 2 months. They recorded their
      levels of discomfort at rest, while chewing, and while biting, as well as their
      analgesic consumption and sleep disturbances. RESULTS: Both treatment modalities
      demonstrated similar levels of initial discomfort. There were no significant sex
      differences. Patients in the traditional fixed appliances group reported
      significantly (P < .05) greater discomfort than patients in the aligner group
      during the first week of active treatment. There was significantly more
      discomfort while chewing than when at rest. Traditional patients also reported
      significantly more discomfort than aligner patients after the first and second
      monthly adjustment appointments. Discomfort after the subsequent adjustments was
      consistently lower than after the initial bonding or aligner delivery
      appointments. A higher percentage of patients in the fixed-appliance group
      reported taking analgesics during the first week for dental pain, but only the
      difference on day 2 was statistically significant. CONCLUSIONS: Patients treated
      with traditional fixed appliances reported greater discomfort and consumed more
      analgesics than patients treated with aligners. This trial was not registered.

PMID- 28753034
TI  - Optimal Regression Method for Near-Infrared Spectroscopic Evaluation of Articular
      Cartilage.
AB  - Near-infrared (NIR) spectroscopy has been successful in nondestructive assessment
      of biological tissue properties, such as stiffness of articular cartilage, and is
      proposed to be used in clinical arthroscopies. Near-infrared spectroscopic data
      include absorbance values from a broad wavelength region resulting in a large
      number of contributing factors. This broad spectrum includes information from
      potentially noisy variables, which may contribute to errors during regression
      analysis. We hypothesized that partial least squares regression (PLSR) is an
      optimal multivariate regression technique and requires application of variable
      selection methods to further improve the performance of NIR spectroscopy-based
      prediction of cartilage tissue properties, including instantaneous, equilibrium,
      and dynamic moduli and cartilage thickness. To test this hypothesis, we conducted
      for the first time a comparative analysis of multivariate regression techniques,
      which included principal component regression (PCR), PLSR, ridge regression,
      least absolute shrinkage and selection operator (Lasso), and least squares
      version of support vector machines (LS-SVM) on NIR spectral data of equine
      articular cartilage. Additionally, we evaluated the effect of variable selection
      methods, including Monte Carlo uninformative variable elimination (MC-UVE),
      competitive adaptive reweighted sampling (CARS), variable combination population
      analysis (VCPA), backward interval PLS (BiPLS), genetic algorithm (GA), and
      jackknife, on the performance of the optimal regression technique. The PLSR
      technique was found as an optimal regression tool (R2Tissue thickness = 75.6%,
      R2Dynamic modulus = 64.9%) for cartilage NIR data; variable selection methods
      simplified the prediction models enabling the use of lesser number of regression
      components. However, the improvements in model performance with variable
      selection methods were found to be statistically insignificant. Thus, the PLSR
      technique is recommended as the regression tool for multivariate analysis for
      prediction of articular cartilage properties from its NIR spectra.

PMID- 28753035
TI  - Quantitative Prevalence, Phenotypic and Genotypic Characteristics of Bacillus
      cereus Isolated from Retail Infant Foods in China.
AB  - Bacillus cereus is an important foodborne pathogen, which can cause severe food
      poisoning. The aim of this study was (i) to evaluate the quantitative prevalence
      of B. cereus in retail prepackaged infant formula and ready-to-eat rice flour in
      China and (ii) to gain the basic information on pheno- and genotypic
      characteristics of B. cereus isolates. We found that 40 out of the 587 samples
      were positive for B. cereus. B. cereus in 3.5% of infant formula samples and 1.0%
      of rice flour samples outnumbered 100 Colony-Forming Units (CFU)/g. B. cereus
      level even attained 103-104 CFU/g in four infant formula samples and one rice
      flour sample. Furthermore, we identified the distribution patterns of toxin genes
      in B. cereus isolates. The results showed that 97.5% of B. cereus isolates
      harbored at least one enterotoxin gene. Antibiotic susceptibility tests revealed
      that all isolated B. cereus strains were resistant to penicillin and 50% of them
      were multidrug resistant. Thirteen new sequence types (STs) and four new alleles
      were identified via multilocus sequence typing. Clonal Complex (CC) ST-205 and CC
      ST-142 were predominant clonal complexes. Interestingly, we revealed the special
      relationship between STs of B. cereus isolates and the geographical distributions
      of infant food manufacturers for the first time. The data implied that B. cereus
      of different STs might have a distinct ecological niche in China. In view of
      relatively high contamination level of enterotoxin- producing B. cereus in a
      proportion of infant foods, especially in those suitable for the <=6-month-old
      infant group, appropriate safety criteria and hygienic control measures for
      infant foods should be drafted in China to prevent B. cereus infection.

PMID- 28753036
TI  - Political Therapeutics: Dialogues and Frictions Around Care and Cure.
AB  - In 1978, Italy passed a law establishing the abolition of the mental hospital. Up
      to that time, the traditional asylums were still governed by the 1904 law that
      positioned psychiatry within the criminal justice system by assigning it the
      function of custodia (control, custody) rather than of cura (care). In the 1960s
      and 1970s, Italian psychiatrist Franco Basaglia initiated a movement of de
      institutionalization of the mentally ill that revolutionized psychiatric care in
      Italy. It also had a deep impact on restructuring the psychiatric system in other
      European and Latin American countries. In this article, I discuss the different
      psychiatric practices and imaginaries that resulted from the movement of
      democratic psychiatry and Basaglia's visions for a community-based and diagnosis
      free care of the mentally ill. I ethnographically trace what I call the "Basaglia
      effect" in today's psychiatric practices, and focus on ethnopsychiatry as a
      counter clinic that emerged from Basaglia's legacy. I reflect on the frictions
      between care and cure that ethnopsychiatry re-articulates and works with in the
      context of contemporary migrations to Europe.

PMID- 28753037
TI  - "Direct" and "Indirect" Methods to Detect Oxidative Stress During Acute or
      Chronic High-Altitude Exposure.

PMID- 28753038
TI  - Physician Experiences With High Value Care in Internal Medicine Residency: Mixed
      Methods Study of 2003-2013 Residency Graduates.
AB  - : Phenomenon: High healthcare costs and relatively poor health outcomes in the
      United States have led to calls to improve the teaching of high value care
      (defined as care that balances potential benefits of interventions with their
      harms including costs) to physicians-in-training. Numerous interventions to
      increase high value care in graduate medical education were implemented at the
      national and local levels over the past decade. However, there has been little
      evaluation of their impact on physician experiences during training and perceived
      preparedness for practice. We aimed to assess trends in U.S. physician
      experiences with high value care during residency over the past decade. APPROACH:
      This mixed-methods study used a cross-sectional survey mailed July 2014 to
      January 2015 to 902 internists who completed residency in 2003-2013, randomly
      selected from the American Medical Association Masterfile. Quantitative analyses
      of survey responses and content analysis of free-text comments submitted by
      respondents were performed. FINDINGS: A total of 456 physicians (50.6%)
      responded. Fewer than one fourth reported being exposed to teaching about high
      value care at least frequently (23.6%, 106/450). Only 43.8% of respondents
      (193/446) felt prepared to use overtreatment guidelines in conversations with
      patients, whereas 85.8% (379/447) felt prepared to participate in shared decision
      making with patients at the conclusion of their training, and 84.4% (380/450)
      reported practicing generic prescribing. Physicians who completed residency more
      recently were more likely to report practicing generic prescribing and feeling
      well prepared to use overtreatment guidelines in conversations with patients (p <
      .01 for both). Insights: In a national survey, recent U.S. internal medicine
      residency graduates were more likely to experience high value care during
      training, which may reflect increased national and local efforts in this area.
      However, being exposed to high value care as a trainee may not translate into
      specific tools for practice. In fact, many U.S. internists reported inadequate
      exposure to prepare them for patient discussions about costs and the use of
      overtreatment guidelines in practice.

PMID- 28753039
TI  - Occupational Exposures and Subclinical Interstitial Lung Disease. The MESA (Multi
      Ethnic Study of Atherosclerosis) Air and Lung Studies.
AB  - RATIONALE: The impact of a broad range of occupational exposures on subclinical
      interstitial lung disease (ILD) has not been studied. OBJECTIVES: To determine
      whether occupational exposures to vapors, gas, dust, and fumes (VGDF) are
      associated with high-attenuation areas (HAA) and interstitial lung abnormalities
      (ILA), which are quantitative and qualitative computed tomography (CT)-based
      measurements of subclinical ILD, respectively. METHODS: We performed analyses of
      participants enrolled in MESA (Multi-Ethnic Study of Atherosclerosis), a
      population-based cohort aged 45-84 years at recruitment. HAA was measured at
      baseline and on serial cardiac CT scans in 5,702 participants. ILA was
      ascertained in a subset of 2,312 participants who underwent full-lung CT scanning
      at 10-year follow-up. Occupational exposures were assessed by self-reported VGDF
      exposure and by job-exposure matrix (JEM). Linear mixed models and logistic
      regression were used to determine whether occupational exposures were associated
      with log-transformed HAA and ILA. Models were adjusted for age, sex,
      race/ethnicity, education, employment status, tobacco use, and scanner
      technology. MEASUREMENTS AND MAIN RESULTS: Each JEM score increment in VGDF
      exposure was associated with 2.64% greater HAA (95% confidence interval [CI],
      1.23-4.19%). Self-reported vapors/gas exposure was associated with an increased
      odds of ILA among those currently employed (1.76-fold; 95% CI, 1.09-2.84) and
      those less than 65 years old (1.97-fold; 95% CI, 1.16-3.35). There was no
      consistent evidence that occupational exposures were associated with progression
      of HAA over the follow-up period. CONCLUSIONS: JEM-assigned and self-reported
      exposures to VGDF were associated with measurements of subclinical ILD in
      community-dwelling adults.

PMID- 28753040
TI  - Evaluation of sofosbuvir, velpatasvir plus voxilaprevir as fixed-dose co
      formulation for treating hepatitis C.
AB  - INTRODUCTION: The fixed-dose combination of three direct-acting antivirals (DAA),
      namely sofosbuvir, velpatasvir and voxilaprevir is the first pangenotypic, single
      tablet regimen developed for the treatment of HCV infection. Areas covered: The
      pharmacokinetics, pharmacodynamics, efficacy and safety of the co-formulation are
      reviewed. Information on drug absorption, distribution, metabolism and excretion
      of each of the three antivirals is evaluated. Finally, antiviral activity, safety
      and potential for drug interactions in phase II/III clinical trials in distinct
      patient populations are discussed. Expert opinion: The triple co-formulation of
      sofosbuvir-velpatasvir-voxilaprevir represents a major step towards HCV
      eradication. It depicts high efficacy even in patients infected with viruses
      harboring resistance-associated substitutions (RAS), including those selected
      after DAA failures. Likewise, very high success rates and good tolerance are seen
      in special patient populations, including decompensated cirrhotics, HIV
      coinfection, organ transplantation or renal insufficiency. A pill once daily for
      8 weeks gives SVR rates above 95%. In prior DAA failures, extending treatment to
      12 weeks maximizes SVR rates.

PMID- 28753041
TI  - Students' Perceptions of Trigger Warnings in Medical Education.
AB  - : Phenomenon: Trigger warnings are verbal statements or written warnings that
      alert students in advance to potentially distressing material. Medical education
      includes numerous subjects frequently identified as triggers, such as abuse,
      rape, self-injurious behaviors, eating disorders, drug and alcohol addiction, and
      suicide. Thus, exploring medical students' perceptions of trigger warnings may
      provide a valuable perspective on the use of these warnings in higher education.
      APPROACH: As part of a larger descriptive, cross-sectional survey study on
      medical education, we assessed 1st- and 2nd-year medical students' perceptions of
      trigger warnings in the preclinical curriculum. Five questions specific to
      trigger warnings explored students' knowledge, prior experience, and perceptions
      of trigger warnings in medical education. Frequencies of individual question
      responses were calculated, and qualitative data were analyzed via content and
      thematic analyses. FINDINGS: Of the 424 medical students invited to participate,
      259 completed the survey (M = 24.8 years, SD + 3.4, 51.4% female, 76.1% White,
      53.7% 1st-year students). Few students (11.2%) were aware of the term trigger
      warning and its definition. However, after being presented with a formal
      definition on the online survey, 38.6% reported having had a professor use one.
      When asked whether they supported the use of trigger warnings in medical
      education, respondents were distributed fairly equally by response (yes = 31.0%,
      maybe = 39.2%, no = 29.7%). Qualitative analysis revealed three themes: (a)
      Trigger Warnings Allow Students to Know What is Coming and Prepare Themselves:
      Respondents believed that trigger warnings would benefit students with a history
      of trauma by providing them additional time to prepare for the material and, if
      appropriate, seek professional help; (b) Students Need to Learn How to Handle
      Distressing Information: Respondents agreed that they needed to learn and cope
      with highly sensitive material because they would be confronted with difficult
      and unexpected situations in clinical practice; and (c) Trigger Warnings Help
      Students Understand the Severity of the Material: Respondents felt that trigger
      warnings may help students understand the severity of the material being covered
      and increase awareness about trauma and its effects on health and well-being.
      Insights: Findings did not reach consensus for or against the use of trigger
      warnings in medical school; however, students emphasized the importance of
      learning how to cope with distressing material. Trigger warnings may represent a
      teaching tool to facilitate classroom discussions about the severity of trauma
      related material and problem-focused coping strategies.

PMID- 28753042
TI  - Increased detection of co-morbidities with evaluation at a dedicated adult Turner
      syndrome clinic.
AB  - OBJECTIVES: Turner syndrome (TS), resulting from complete/partial X chromosomal
      monosomy, is associated with multiple co-morbidities and increased mortality.
      Although multidisciplinary management is recommended, TS women's health care is
      sub-optimal. This study evaluates a multidisciplinary adult TS service. METHODS:
      Retrospective cohort study of 82 patients attending the quarterly TS clinic from
      December 2003 to December 2014. Evaluation included (1) demographics, (2) TS
      standardized co-morbidity screening, and (3) estrogen therapy use. Data analysis
      involved frequency statistics, T tests and polychoric correlation analysis.
      RESULTS: Median age at TS diagnosis was 14 years (range 0-65 years), with 12% of
      women aged >18 years. Median age at initial consultation was 31 years (range 16
      65 years). Only 14% of patients were transition program referrals. XO karyotype
      occurred in 30%. Primary amenorrhea predominated; however, 37% of TS women were
      not taking estrogen therapy. The proportion of patients not previously screened
      (44-76%) and those with positive screening diagnoses (5-53%) varied according to
      co-morbidity. The mean (+/- standard deviation) number of co-morbidities
      identified increased following TS clinic screening (7.0 +/- 2.6 post-screening
      vs. 4.4 +/- 2.3 pre-screening; p < 0.0001). Polychoric correlation analysis
      identified particular co-morbidity groupings (including metabolism-related) and
      increased co-morbidities with primary amenorrhea. CONCLUSION: A multidisciplinary
      adult TS clinic improves health surveillance with increased identification of co
      morbidities and initiation of estrogen therapy.

PMID- 28753043
TI  - The Impact of Storage Conditions on the Stability of Lactobacillus rhamnosus GG
      and Bifidobacterium animalis subsp. lactis Bb12 in Human Milk.
AB  - Human milk is the optimal source of complete nutrition for neonates and it also
      guides the development of infant gut microbiota. Importantly, human milk can be
      supplemented with probiotics to complement the health benefits of breastfeeding.
      Storage of human milk for limited periods of time is often unavoidable, but
      little is known about the effect of different storage conditions (temperature) on
      the viability of the added probiotics. Therefore, in this study, we evaluated how
      different storage conditions affect the viability of two specific widely used
      probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp.
      lactis (Bb12), in human milk by culturing and quantitative polymerase chain
      reaction. Our results indicate that LGG and Bb12 remained stable throughout the
      storage period. Thus, we conclude that human milk offers an appropriate matrix
      for probiotic supplementation.

PMID- 28753044
TI  - Severe bark scorpion envenomation in adults.
AB  - INTRODUCTION: The preponderance of medical literature regarding severe bark
      scorpion envenomation describes pediatric patients; however, the majority (>66%)
      of annual poison center calls pertain to adults. This retrospective review sought
      to evaluate the clinical manifestations of adults with severe Centruroides
      sculpturatus envenomation and determine if significant morbidity occurred.
      METHODS: This is a retrospective review of adults presenting to a single tertiary
      referral center with Grade-III or Grade-IV scorpion envenomation from 1 January
      2007 to 3 March 2013. The primary objective is to describe clinical findings,
      treatment strategies, complications and short-term outcomes. RESULTS: Thirty
      three patients were included; 61% were female (20/33), average age was 40.7 (19
      81) years. The average time to healthcare facility was 142 (14-720) minutes. The
      most common signs and symptoms of envenomation were: pain/paresthesias 94%,
      opsoclonus 82%, excessive motor activity 76%, visual disturbance 76%.
      Benzodiazepines 85% (29/33) and opioids 83% (28/33) were the most frequently used
      agents to control envenomation. Cardiac evaluation was performed in 24% of
      patients, 6% were pregnant and underwent fetal monitoring, 6% were intubated and
      3% developed rhabdomyolysis. Average length of stay (LOS) was 28.3 (1.5-307)
      hours; 58% (19/33) required hospital admission. Four patients had LOS >48 h, with
      pre-existing cardiac disease, substance misuse disorder, acute ethanol withdrawal
      and medical errors identified as factors contributing to prolonged LOS.
      CONCLUSIONS: Bark scorpion envenomation in adults may be severe, necessitating
      medical intervention and hospital admission. Comorbid conditions and
      complications arising from treatment may contribute to prolonged LOS.

PMID- 28753045
TI  - An internet-based survey of 96 German-speaking users of "bath salts": frequent
      complications, risky sexual behavior, violence, and delinquency.
AB  - OBJECTIVE: To define the demographics of German-speaking "bath salt" users.
      DESIGN: Prospective web-based survey of volunteer users of "bath salts". Subject
      recruitment/exclusion: Participation was solicited by posts in web forums
      frequented by users of synthetic cathinones. An invitation to participate was
      also disseminated via regional drug information centers. Responses were discarded
      if participants refused data analysis, provided incomplete surveys, were under 18
      years of age (five cases), and in case of clearly improbable answers (i.e., two
      cases with profanity typed in free-form input fields). Overall 96 out of 180
      participants provided complete questionnaires. These were further analyzed.
      RESULTS AND CONCLUSIONS: 74% of respondents were male. 41% were under the age of
      30 and a further 38% between 30 and 39 years old. Cathinones were used on more
      than 10 days in the preceding year by 62% of study subjects. The nasal and
      intravenous routes of administration were most often used. About 80% of
      respondents reported binge use. There were frequent co-administrations of opioids
      and opiates. The most common complication was prolonged confusion (47%). 16% had
      been involuntarily confined. One third had thoughts of violence and 16% acted on
      these thoughts either against themselves or others. About 44% reported high-risk
      sexual activity under the influence of cathinones. About 31% had driven or ridden
      a bike while intoxicated. About 6% had problems with law-enforcement for selling
      cathinones and 16% for crimes committed under the influence of cathinones. In
      conclusion, cathinone users are typically young males in their twenties and
      thirties. Most are experienced drug users, particularly of alcohol and
      opiates/opioids. The impact on society is tremendous as evidenced by high rates
      of self-reported violence, high-risk sexual activity, crimes, and traffic
      violations.

PMID- 28753046
TI  - Levetiracetam in toxic seizures.
AB  - BACKGROUND/OBJECTIVES: The use of levetiracetam (LEV) in the management of drug
      induced seizures has not been systematically investigated. Repetitive and
      continuous seizures that do not respond to benzodiazepines require second line
      therapy. Levetiracetam has a unique receptor binding site, rapid absorption, no
      known cardiac effects at therapeutic doses, and is theoretically a good candidate
      for use in drug-induced seizures. We evaluate the safety of LEV and its
      association with seizure cessation in this retrospective chart review of patients
      who received LEV as a control agent in drug-induced seizures. METHODS: We
      identified the medical records of patients presenting to an urban, level 1 trauma
      center between 1 January 2010 and 31 May 2015 by ICD-9 codes based on the
      following: (1) a poisoning diagnosis, (2) a seizure diagnosis, and (3)
      administration of LEV. We included patients with a drug-induced seizure based on
      history, electroencephalogram results, blood alcohol concentrations, urine drug
      screens, and adequate documentation. We excluded patients with alcohol
      withdrawal, anoxic brain injury, subtherapeutic concentrations of other
      antiepileptics, hypoglycemia, and pseudoseizures. Primary outcomes of interest
      included cessation of active seizures or the prevention of seizure recurrence. We
      assessed safety by the presence or absence of adverse drug effects (ADE)
      attributed to the administration of LEV. RESULTS: Thirty-four patients met
      inclusion and exclusion criteria. Half of the study cohort (17) presented with
      generalized tonic-clonic seizures (TCS); half (17) presented in generalized
      convulsive status epilepticus (GCSE). Six patients in GCSE received LEV during
      their seizures; 2 also received fosphenytoin. One improved immediately following
      LEV administration, and the remaining 5 had seizure control. Eleven GCSE patients
      (65%) remained seizure free after LEV therapy. The patients with TCS (17)
      received LEV after seizure(s) control. Sixteen (94%) were seizure-free during
      their hospital course. We found no adverse drug effects. In total, 27 of 34
      patients (79%) had a return to baseline neurological and physical health. Six had
      long-term sequelae; none of which are known LEV side-effects. We identified 46
      toxic substances and 22 known seizurogenic agents (48%). The median length of
      stay was 3.7 days (0.4-96), and the median duration of in-hospital LEV therapy
      was 1.6 days (0-49). CONCLUSIONS: Levetiracetam used as a second-line agent was
      associated with control of drug-induced seizures and prevention of seizure
      recurrence without obvious adverse effects. A prospective study is needed to
      confirm these results.

PMID- 28753047
TI  - Leadership Identity Development Through Reflection and Feedback in Team-Based
      Learning Medical Student Teams.
AB  - PROBLEM: Studies on leadership identity development through reflection with Team
      Based Learning (TBL) in medical student education are rare. We assumed that
      reflection and feedback on the team leadership process would advance the
      progression through leadership identity development stages in medical students
      within the context of classes using TBL. INTERVENTION: This study is a quasi
      experimental design with pretest-posttest control group. The pretest and posttest
      were reflection papers of medical students about their experience of leadership
      during their TBL sessions. In the intervention group, TBL and a team-based,
      guided reflection and feedback on the team leadership process were performed at
      the end of all TBL sessions. In the other group, only TBL was used. The Stata 12
      software was used. Leadership Identity was treated both as a categorical and
      quantitative variable to control for differences in baseline and gender
      variables. Chi-square, t tests, and linear regression analysis were performed.
      CONTEXT: The population was a cohort of 2015-2016 medical students in a TBL
      setting at Tehran University of Medical Sciences, School of Medicine. Teams of
      four to seven students were formed by random sorting at the beginning of the
      academic year (intervention group n = 20 teams, control group n = 19 teams).
      OUTCOME: At baseline, most students in both groups were categorized in the
      Awareness and Exploration stage of leadership identity: 51 (52%) in the
      intervention group and 59 (55%) in the control group: uncorrected chi2(3) = 15.6,
      design-based F(2.83, 108) = 4.87, p = .003. In the posttest intervention group,
      36 (36%) were in exploration, 33 (33%) were in L-identified, 20 (20%) were in
      Leadership Differentiated, and 10 (10%) were in the Generativity. None were in
      the Awareness or Integration stages. In the control group, 3 (20%) were in
      Awareness, 56 (53%) were in Exploration, 35 (33%) were in Leader Identified, 13
      (12%) were in Leadership Differentiated. None were in the Generativity and
      Integration stages. Our hypothesis was supported by the data: uncorrected chi2(4)
      = 18.6, design-based F(3.77, 143) = 4.46, p = .002. The mean of the leadership
      identity in the pretest, intervention group equaled 1.93 (SD = 0.85) and the
      pretest, control group mean was 2.36 (SD = 0.86), p = .004. The mean of the
      posttest, intervention group was 3.04 (SD = 0.98) and posttest, control group
      mean was 2.54 (SD = 0.74), T = -4.00, design df = 38, p < .001, and adjusted on
      baseline and gender T = -8.97, design df = 38, p < .001. LESSONS LEARNED:
      Reflection and feedback on the team leadership process in TBL advances the
      progression in stages of leadership identity development in medical students.
      Although the TBL strategy itself could have an impact on leadership identity
      development, this study demonstrates that when a reflection and feedback on
      leadership intervention are added, there is much greater impact.

PMID- 28753048
TI  - Initial diffusion-weighted MRI and long-term neurologic outcomes in charcoal
      burning carbon monoxide poisoning.
AB  - CONTEXT: This study assessed the results of diffusion-weighted imaging (DWI) at
      presentation for acute charcoal-burning carbon monoxide (CO) poisoning and
      investigated whether the initial DWI results can predict long-term neurologic
      outcomes. METHODS: The study included 128 patients who suffered from CO poisoning
      after burning charcoal and underwent DWI. These patients were divided into two
      groups based on imaging results: a normal DWI group and an abnormal DWI group.
      Data regarding clinical courses and long-term neurologic outcomes (persistent
      severe neurologic sequelae) were collected and compared. RESULTS: The rate of
      abnormal DWI findings at presentation was 23.4%, and the most common site of
      abnormalities was the globus pallidus. All lesions in abnormal DWI had decreased
      apparent diffusion coefficient (ADC) values. The long-term neurologic state was
      assessed at a median follow-up of 19.5 months, and the frequency of poor long
      term neurologic outcome was significantly higher in the abnormal DWI group (40.0%
      in the abnormal DWI group vs. 1.0% in the normal DWI group; p < .001). Abnormal
      DWI (odds ratio [OR]): 31.3, 95% confidence interval [CI]: 2.5-397) and old age
      (OR 1.1, 95% CI: 1.001-1.13) were independent factors for poor long-term
      neurologic outcomes, whereas the Glasgow Coma Scale score at presentation (OR:
      0.7, 95% CI: 0.6-0.9) was negatively associated with the risk of poor long-term
      neurologic outcome. CONCLUSIONS: In cases involving CO poisoning due to charcoal
      burning, DWI at presentation may help predict the long-term neurological outcome
      after discharge.

PMID- 28753049
TI  - Medical Students' Use of Different Coping Strategies and Relationship With
      Academic Performance in Preclinical and Clinical Years.
AB  - : Phenomenon: Medical students' coping abilities are important for academic
      success and emotional health. The authors explored differences in students' use
      of active, problem-solving strategies and emotional, inwardly directed
      approaches; the change in coping strategies used during medical school; and
      coping strategy impact on performance. APPROACH: One hundred eighty-three
      students completed the Ways of Coping Scale at matriculation and end of the 2nd
      and 3rd years. Frequency of each of 8 ways of coping, changes in coping strategy
      use over time, and relationship of coping method with preclinical and clinical
      scores were calculated. FINDINGS: Students varied widely in use of coping
      mechanisms. Over time, students shifted to using emotional strategies more
      frequently while decreasing their use of active strategies. Coping strategies
      were unrelated to preclinical academic performance (R2 = .09, adjusted R2 = .04,
      ns) but were related to clinical performance (R2 = .23, adjusted R2 = .18, p <
      .0001), with active coping associated with higher performance and emotional
      methods associated with lower performance. Insights: Students decreased use of
      active coping strategies and increased use of emotional coping strategies over
      time, but emotional strategies were associated with poorer clinical academic
      performance. These shifts in coping methods may be detrimental to student
      performance and learning. Improving students' ability to cope should be an
      educational priority.

PMID- 28753050
TI  - Symptoms of Depression and ADHD in Relation to Stimulant Medication Misuse Among
      College Students.
AB  - BACKGROUND: The misuse of stimulant medications, commonly used for the treatment
      of attention-deficit/hyperactivity disorder (ADHD), is a concern on college
      campuses. OBJECTIVE: This study sought to examine the relations between the
      misuse of stimulant medications and symptoms of depression and ADHD. METHOD:
      Eight hundred and ninety students ages 18-26 from one public university took a
      web-based survey including rating scales measuring symptoms of depression and
      ADHD. RESULTS: The prevalence rate of misuse in the past year was 23%. Symptoms
      of depression were significantly related to misuse; however, once symptoms of
      ADHD were included in the analysis, depression was no longer a significant
      predictor. Further, there was not a significant interaction between ADHD and
      depression, but symptoms of ADHD were significantly related to misuse.
      Conclusions/Importance: Results suggest that attention difficulties may be one of
      the most important factors in predicting stimulant medication misuse. Therefore,
      prevention efforts to reduce the misuse of stimulant medication would be most
      successful when targeting students with symptoms of inattention.

PMID- 28753051
TI  - A review of hydrolifting: A new modality for skin rejuvenation.
AB  - BACKGROUND: Hydrolifting is a newly developed modality of skin rejuvenation,
      which enhances overall facial volume augmentation and recovers skin thickness
      through multi-pass HA injection. Although it is commonly performed, only a few
      articles have reported on the rejuvenating effects of hydrolifting. Moreover,
      clear protocols and possible mechanisms of the procedure have not been
      elucidated. OBJECTIVE: To define a novel technique for injecting HA and to
      clarify how to choose an appropriate HA filler based on the procedural purpose.
      METHODS: This article is based on a review of the medical literature and the
      authors' clinical experience in investigating and treating skin wrinkles with the
      hydrolifting method. RESULTS: In hydrolifting, HA filler serves as a hydration
      source, dermal volumizer, and stimulator of dermal collagen and antioxidants.
      Hydrolifting is frequently indicated in minor wrinkles, minor volume depletion
      and rough skin texture. CONCLUSION: The hydrolifting method is a newly introduced
      antiaging treatment modality. It effectively covers the blind spots of
      conventional HA injection, such as infraorbital, perioral and hand dorsal
      wrinkles. However, further investigations are needed to reach a consensus on the
      basic concepts of treatment, choice of appropriate fillers and optimal technique
      in hydrolifting.

PMID- 28753052
TI  - Physicians' and pharmacists' information provision and patients' psychological
      distress.
AB  - Providing information related to medication has many benefits for patients.
      However, patients' conflicting perceptions about medical information provided by
      physicians and pharmacists may be associated with their psychological distress
      regarding treatment and medication. This study investigated associations between
      patients' perceptions of agreement between physicians and pharmacists about
      medical information and improvements in their psychological distress. It also
      clarified the specific relationships of their perceptions with psychological
      distress. A cross-sectional survey was conducted in Japanese community pharmacy
      settings. Pharmacists approached 1,500 patients visiting community pharmacies and
      provided them with questionnaire packages. Patients completed the questionnaires
      at home and returned them to the researchers by mail. Multivariate logistic
      regression analysis and signal detection analysis were conducted to examine
      associations of patients' perceptions of information agreement with improvement
      in psychological distress. Measures of improvement in worry and anxiety about
      disease, improvement in worry and anxiety about medication, and improvement in
      depressive mood were used to assess alleviation of psychological distress. A
      total of 645 patients returned the questionnaires; 628 contributed to the data.
      Multivariate logistic regression analyses clarified that patients' perceptions of
      agreement in information regarding need for medication, methods for adverse drug
      reaction reduction, adverse drug reaction symptoms, coping with forgetting to
      take medication, and advice for daily life were significantly associated with
      improvements in psychological distress. Furthermore, signal detection analysis
      showed that several combinations of patients' perceptions of agreement between
      physicians and pharmacists about specific medical information were also
      significantly associated with improvement in psychological distress. Consistent
      information provision by physicians and pharmacists could contribute to decreased
      psychological distress in patients, and consequently to adherence to treatment
      and taking medication.

PMID- 28753053
TI  - Development of Child and Family-Centered Engagement Guidelines for Clinical
      Administration of the Challenge to Measure Advanced Gross Motor Skills: A
      Qualitative Study.
AB  - AIMS: This article describes a qualitative study aimed at producing child
      centered guidelines for the administration of a measure of children's advanced
      gross motor skills, the Challenge. The purpose of the guidelines is to promote
      collaborative interpretation and application of results. METHODS: The study was
      conducted in three Canadian cities and included 31 children with cerebral palsy
      (GMFCS Level I or II) ages 8 to 18 and one parent/caregiver per child (N = 62
      participants). Following Challenge administration, each child and one of their
      caregivers took part in separate qualitative interviews. Analyses were oriented
      to exploring understandings of the purposes of testing, impressions of the
      child's performance, and perceptions of how results might inform activity choices
      and interventions. RESULTS: Three themes were generated: investments in doing
      well; I know my child/myself; and caregivers' interpretations of child's
      performance. Themes were then integrated with principles of child and family
      centered care to develop The Challenge Engagement Guidelines directed at reducing
      test anxiety and enhancing shared decision making. CONCLUSIONS: The Guidelines
      are the first of their kind to integrate child and family-centered principles
      into the administration protocol of a motor measure. Although developed for the
      Challenge, the principles have applicability to other rehabilitation measures.

PMID- 28753054
TI  - Parents' Perception of Receiving Family-Centered Care for Their Children with
      Physical Disabilities: A Meta-Analysis.
AB  - AIMS: Understanding parent perceptions of family-centered care (FCC) is important
      to improve processes and outcomes of children's services. OBJECTIVE: A systematic
      review and meta-analysis of research on the Measures of Processes of Care (MPOC
      20) were performed to determine the extent parents of children with physical
      disabilities perceive they received FCC. METHODS: A comprehensive literature
      search was conducted using four databases. A total of 129 studies were retrieved;
      15 met the criteria for the synthesis. Meta-analysis involving 2,582 mothers and
      fathers of children with physical disabilities mainly cerebral palsy was
      conducted for the five scales of the MPOC-20. RESULTS: Aggregated mean ratings
      varied from 5.0 to 5.5 for Providing Specific Information about the Child;
      Coordinated and Comprehensive Care; and Respectful and Supportive Care
      (relational behaviors) and Enabling and Partnership (participatory behaviors)
      indicating that, on average, parents rated FCC as having been provided to "a
      fairly great extent." The aggregated mean rating was 4.1 for Providing General
      Information, indicating FCC was provided "to a moderate extent." CONCLUSIONS:
      Service providers are encouraged to focus on child and family needs for general
      information. Research is needed to better understand parent perspectives of
      service provider participatory behaviors which are important for engaging
      families in intervention processes.

PMID- 28753055
TI  - The association of isoconazole-diflucortolone in the treatment of pediatric tinea
      corporis.
AB  - BACKGROUND: Tinea corporis is a common mycotic infection in children.
      Staphylococcus aureus superinfections may be observed in atopic children with
      tinea corporis suffering from severe pruritus and consequent scratching.
      OBJECTIVE: From 2006 to 2011, we observed 288 children with mycologically proven
      tinea corporis. In 39 of them (13.5%) tinea corporis was superinfected by S.
      aureus: all these children were affected by atopic dermatitis. We interpreted
      these bacterial superinfections as the clinical result of scratching due to
      pruritus. METHODS: In 2012, we decided to treat all children with a single lesion
      of tinea corporis with a combination of 1% isoconazole nitrate and 0.1%
      diflucortolone valerate cream (one application/day for 5-7 days), followed by a
      treatment with isoconazole or clotrimazole or ciclopirox cream (two
      applications/day for two weeks). RESULTS: From 2012 to 2014, we observed 108
      children with tinea corporis confirmed by mycological examinations. Clinical and
      mycological recovery was observed in 93 of them (86.1%). Only four of these
      children (3.7%) developed S. aureus superinfections. CONCLUSIONS: Our study in
      atopic children with tinea corporis superinfected by S. aureus confirms that a
      topical therapy with the association isoconazole-diflucortolone is useful and
      safe.

PMID- 28753056
TI  - Gamma-Irradiated Luteolin Inhibits 3-Isobutyl-1-Methylxanthine-Induced
      Melanogenesis Through the Regulation of CREB/MITF, PI3K/Akt, and ERK Pathways in
      B16BL6 Melanoma Cells.
AB  - Luteolin was gamma irradiated at doses of 0, 15, 30, 50, 70, and 100 kGy. We
      observed that the luteolin peak decreased simultaneously with the appearance of
      new radiolytic peaks, using high-performance liquid chromatography (HPLC). The
      highest new radiolytic peak (GLM) of radiolytic product in gamma-irradiated
      luteolin was observed at a dose of 70 kGy, and the GLM was identified by nuclear
      magnetic resonance and high-performance-liquid-chromatography-quadrupole-time-of
      flight (HPLC-Q-TOF) mass spectrometry. We examined whether 70 kGy gamma
      irradiated luteolin has more effective anti-melanogenic effects than intact
      luteolin. Seventy kilograys of gamma-irradiated luteolin inhibited melanin
      synthesis and intracellular tyrosinase activity without cytotoxicity, whereas the
      intact luteolin-treated group did not show anti-melanogenic activity in 3
      isobutyl-1-methylxanthine-stimulated B16BL6 melanoma cells. The expression of
      melanogenic enzymes, such as tyrosinase, tyrosinase-related protein (TRP)-1, and
      TRP-2, was decreased by 70 kGy gamma-irradiated luteolin treatment, owing to the
      suppression of microphthalamia-associated transcription factor and 3',5'-cyclic
      adenosine monophosphate (cAMP) response element binding protein. In addition,
      gamma-irradiated luteolin decreased the phosphorylation of phosphoinositide 3
      kinase (PI3K)/Akt and extracellular regulated kinase (ERK). The anti-melanogenic
      effects of 70 kGy gamma-irradiated luteolin were attenuated by the treatment of
      two specific inhibitors (PD98059 and LY294002), and these results indicate that
      the anti-melanogenic effects were mediated by ERK and PI3K signaling pathways.
      Therefore, our findings suggest that gamma-irradiated luteolin can be a potential
      cosmeceutical agent for skin whitening.

PMID- 28753057
TI  - Vesicles: Potential nano carriers for the delivery of skin cosmetics.
AB  - In the present scenario, consumers are searching for personal care products that
      supply multiple benefits with minimal efforts. The outcome has been the
      introduction of nanotechnology-based cosmetic products that are safe to use and
      results driven. Some topical cosmetics can act efficaciously when they reach
      their target sites present in the deeper layers of the skin. The main problem
      with delivering active ingredients across the skin is the barrier function of the
      skin. Therefore, to get the maximum benefit from cosmetic products and to
      overcome the problems associated with their skin penetration, scientists are
      investigating various strategies to overcome these barrier properties. Vesicular
      carriers have been claimed to improve the topical delivery of active ingredients.
      This review offers a brief overview of current approaches in the research and
      development of vesicular carriers to improve the delivery and performance of
      active ingredients present in the cosmetics.

PMID- 28753058
TI  - Attitudes and perceptions from nursing and medical students towards the other
      profession in relation to wound care.
AB  - Lack of nurse-physician collaboration in wound care may result in prolonged
      healing times for patients. In order to facilitate future professional
      collaboration, undergraduate learning activities in interprofessional education
      (IPE) have been proposed. The aim of this study was to investigate nursing and
      medical students' attitudes and perceptions towards each other's future
      professions and interprofessional collaboration in wound care. Nursing and
      medical students took part in an interprofessional learning activity about wound
      care. Data were collected using the Jefferson Scale of Attitudes towards
      Physician-Nurse Collaboration questionnaire to student groups before and after an
      IPE activity (pooled n = 221). Focus groups were conducted to deepen the
      knowledge about students' attitudes and perceptions. The results showed high
      scores on the attitude scale (mean 53.2, possible maximum = 60) both before and
      after IPE, indicating positive attitudes towards nurse-physician collaboration.
      Nursing students scored higher than medical students both pre-IPE (p < 0.001) and
      post-IPE (p = 0.006). However, no difference on scale scores could be identified
      between pre- and post-IPE. The following themes emerged in the analysis of focus
      group discussions: "Approaching patient care from different perspectives," "Need
      for collaboration and clear professional roles in practice," "Structures
      hindering future collaboration," and "IPE as a tool for professional practice and
      roles." The shared learning activity provided insights into the other
      profession's competence. This kind of learning activity may increase future
      interprofessional collaboration, and thus, improve wound care.

PMID- 28753059
TI  - Growth of Salmonella spp. and Escherichia coli O157:H7 on Fresh-Cut Fruits Stored
      at Different Temperatures.
AB  - The objective of this work was to determine the growth potential of Salmonella
      spp. and Escherichia coli O157:H7 on fresh-cut honeydew melon, cantaloupe,
      watermelon, pitaya, mango, papaya, and pineapple stored at 5 degrees C, 13
      degrees C, and 25 degrees C. The results showed that both pathogens were able to
      grow on fresh-cut fruits except fresh-cut pineapple at 13 degrees C and 25
      degrees C. Salmonella spp. grew more rapidly on fresh-cut honeydew melon,
      cantaloupe, watermelon, and mango than did E. coli O157:H7 at 13 degrees C. The
      growth of both species was inhibited on fresh-cut pineapple, with that of
      Salmonella spp. being particularly pronounced. Naturally occurring microbiota
      populations on fresh-cut fruits increased significantly at 13 degrees C and 25
      degrees C, but no significant changes in growth were observed for Salmonella
      spp., E. coli O157:H7, or natural microbiota species at 5 degrees C. The study
      therefore emphasizes the importance of strict temperature control from processing
      to consumption, including transportation, distribution, storage, and handling in
      supermarkets and by consumers.

PMID- 28753060
TI  - Workshop on Recent Issues in Bioanalysis (WRIB) Poster Award winners 2017.
AB  - The 11th WRIB held in Los Angeles, CA, USA in April 2017. It drew over 750
      professionals representing large Pharmas, Biotechs, CROs and multiple regulatory
      agencies from around the world, from the global bioanalytical community.
      Bioanalysis and Bioanalysis Zone are very proud to be supporting the WRIB Poster
      Awards again this year, and we feature the profiles of the authors of the winning
      posters. Visit www.bioanalysis-zone.com to see the winning posters in full.

PMID- 28753061
TI  - Low-Dose Ionizing Radiation Exposure, Oxidative Stress and Epigenetic Programing
      of Health and Disease.
AB  - Ionizing radiation exposure from medical diagnostic imaging has greatly increased
      over the last few decades. Approximately 80% of patients who undergo medical
      imaging are exposed to low-dose ionizing radiation (LDIR). Although there is
      widespread consensus regarding the harmful effects of high doses of radiation,
      the biological effects of low-linear energy transfer (LET) LDIR is not well
      understood. LDIR is known to promote oxidative stress, however, these levels may
      not be large enough to result in genomic mutations. There is emerging evidence
      that oxidative stress causes heritable modifications via epigenetic mechanisms
      (DNA methylation, histone modification, noncoding RNA regulation). These
      epigenetic modifications result in permanent cellular transformations without
      altering the underlying DNA nucleotide sequence. This review summarizes the major
      concepts in the field of epigenetics with a focus on the effects of low-LET LDIR
      (<100 mGy) and oxidative stress on epigenetic gene modification. In this review,
      we show evidence that suggests that LDIR-induced oxidative stress provides a
      mechanistic link between LDIR and epigenetic gene regulation. We also discuss the
      potential implication of LDIR exposure during pregnancy where intrauterine fetal
      development is highly susceptible to oxidative stress-induced epigenetic
      programing.

PMID- 28753062
TI  - Long Noncoding RNA H19 Acts as a Competing Endogenous RNA to Mediate CTGF
      Expression by Sponging miR-455 in Cardiac Fibrosis.
AB  - Cardiac fibrosis is closely related to multiple cardiovascular system diseases,
      and noncoding RNAs (ncRNAs), including long noncoding RNA (lncRNA) and microRNA
      (miRNA), have been reported to play a vital role in fibrogenesis. The present
      study aims to investigate the potential regulatory mechanism of lncRNA H19 and
      miR-455 on fibrosis-associated protein synthesis in cardiac fibroblasts (CFs).
      miRNA microarray assay revealed 34 significantly dysregulated miRNAs, including
      13 upregulated miRNAs and 21 downregulated miRNAs. Among these aberrantly
      expressed miRNAs, we paid attention to miR-455, which was significantly
      downregulated in diabetic mouse myocardium and Ang II-induced CFs. Loss- and gain
      of-function experiments showed that miR-455 expression levels were negatively
      correlated with collagen I and III expression in Ang II-induced CFs.
      Bioinformatic prediction programs (TargetScan, miRanda, starBase) predicted that
      miR-455 targeted connective tissue growth factor (CTGF) and H19 with
      complementary binding sites at the 3'-untranslated region, which was validated by
      luciferase reporter assay. Functional validation assay demonstrated that H19
      knockdown could enhance the antifibrotic role of miR-455 and attenuate the CTGF
      expression and further decrease fibrosis-associated protein synthesis (collagen
      I, III, and alpha-SMA). The present study reveals a novel function of the H19/miR
      455 axis targeting CTGF in cardiac fibrosis, suggesting its potential therapeutic
      role in cardiac diseases.

PMID- 28753063
TI  - Association Between ADRB2 Genetic Polymorphisms and the Risk of Chronic
      Obstructive Pulmonary Disease: A Case-Control Study in a Chinese Population.
AB  - OBJECTIVE: This study was designed to investigate the association between single
      nucleotide polymorphisms (SNPs) of the beta2-adrenergic receptor (ADRB2) gene and
      the risk of chronic obstructive pulmonary disease (COPD) in a Chinese population.
      METHODS: From January 2010 to October 2014, 261 COPD patients were selected as
      the case group and 239 healthy subjects were selected as the control group.
      Pulmonary function tests were performed to detect forced vital capacity (FVC), 1
      s forced expiratory volume (FEV1), and FEV1/FVC (%). rs1042711, rs1042714, and
      rs1042718 were selected as tagSNPs of the ADRB2 gene from the HapMap database in
      accordance with previous studies. The ADRB2 genotypes were established by real
      time polymerase chain reaction assays using TaqMan-labeled probes. The
      relationships between the ADRB2 polymorphisms and COPD risk were estimated using
      logistic regression analyses. RESULTS: The frequency of the genotypes and alleles
      of rs1042711 in ADRB2 showed a significant difference between the COPD and
      control groups (p < 0.05); compared with the CC genotype, the non-CC genotypes
      showed an increased COPD risk (p = 0.002). Compared with the CC haplotype, the TG
      haplotype increased COPD risk, while the CG haplotype reduced COPD risk for
      normal individuals. Compared with the CC genotype, the TT genotype showed
      significantly lower FEV1 and FEV1/FVC (p = 0.022, p = 0.0191, respectively). Both
      the TC and TG haplotypes showed lower FEV1 and FEV1/FVC in comparison with the CC
      haplotype (both p < 0.05). The results of logistic regression analysis showed
      that rs1042711 of ADRB2 and smoking history were associated with COPD risk (both
      p < 0.05). CONCLUSION: It is indicated that the TT genotype of rs1042711 and
      smoking pack years are both risk factors for COPD.

PMID- 28753064
TI  - One-year outcomes of early-crossover patients in a cohort receiving nonoperative
      care for lumbar disc herniation.
AB  - OBJECTIVE The authors comprehensively studied the recovery course and 1-year
      outcomes of early-crossover patients who were randomized to the nonoperative care
      arm of the Leiden-The Hague Spine Intervention Prognostic Study. The primary goal
      was to gain insight into the differences in the recovery patterns of early
      crossover patients and those treated nonoperatively; secondary goals were to
      identify predictors of good 1-year outcomes, and to understand when and why
      patients were likely to cross over. METHODS Individual EuroQol-5D scores were
      obtained at baseline and at 2, 4, 8, 12, 26, 38, and 52 weeks for 142 patients.
      Early-crossover patients were defined as those electing to undergo surgery during
      the first 12 weeks of treatment. Crossover and noncrossover groups were compared
      using Kruskal-Wallis, Wilcoxon-Mann-Whitney, and chi-square tests. Linear mixed
      effects models were used to examine the growth trajectories of crossover and
      noncrossover groups. Recursive partitioning trees were used to model crossover
      events and the timing of crossover decisions. Multivariable logistic regression
      models were used to identify predictors of good 1-year outcomes. RESULTS Of the
      142 patients randomized to receive prolonged nonoperative care, 136 were selected
      for the study. In this cohort, 43/136 (32%) opted for surgery, and 31/43 (72%) of
      crossover events occurred before the 12-week time point. Early-crossover patients
      had significantly greater functional impairment at Week 2 than noncrossover
      patients (p = 0.031), but experienced greater recovery by 26 weeks and better 1
      year outcomes (p = 0.045). Patients who did not experience an improvement in
      their symptoms between 2 and 8 weeks were more likely to cross over (OR 3.5, 95%
      CI 1.2-10.1; p = 0.01). Recursive partitioning trees were able to identify
      crossover patients with 76% accuracy. Regression models suggested that better
      recovery at 26 weeks (p < 0.01) was predictive of good 1-year outcome; declining
      health status between Weeks 4 and 8 was negatively predictive of good outcome (p
      < 0.01). CONCLUSIONS This study is the first to comprehensively analyze the
      recovery and outcomes of crossover patients, and compare them to nonoperatively
      treated patients. The results suggest that patients who have a low EuroQol-5D
      score during the early weeks of treatment and who do not respond to nonoperative
      care during the first few weeks of treatment are most likely to cross over. Early
      crossover patients experience a greater rate of recovery and more frequently have
      a good 1-year outcome when compared with nonoperatively treated patients. The
      current results motivate a broader investigation into the timing of surgery and
      the identification of patient populations that will be most benefited by early
      surgical treatment for lumbar disc herniation.

PMID- 28753065
TI  - Patient-reported outcome scores underestimate the impact of major complications
      in patients undergoing spine surgery for degenerative conditions.
AB  - OBJECTIVE Patient-reported outcomes (PROs) such as the Oswestry Disability Index
      (ODI) and EuroQol-5D (EQ-5D) are widely used to evaluate treatment outcomes
      following spine surgery for degenerative conditions. The goal of this study was
      to use the Charlson Comorbidity Index (CCMI) as a measure of general health
      status, for comparison with standard PROs. METHODS The authors examined serial
      CCMI scores, complications, and PROs in 371 patients treated surgically for
      degenerative lumbar spine conditions who were enrolled in the Quality and
      Outcomes Database from a single center. The cohort included 152 males (41%) with
      a mean age of 58.7 years. Patients with no, minor, or major complications were
      compared at baseline and at 1 year postoperatively. RESULTS Minor complications
      were observed in 177 patients (48%), and major complications in 34 (9%). There
      were no significant differences in preoperative ODI, EQ-5D, or CCMI among the 3
      groups. At 1 year, there was a significantly greater deterioration in CCMI in the
      major complication group (1.03) compared with the minor (0.66) and no
      complication groups (0.44, p < 0.006), but no significant difference in ODI or EQ
      5D. CONCLUSIONS Despite equivalent improvements in PROs, patients with major
      complications actually had greater deterioration in their general health status,
      as evidenced by worse CCMI scores. Because CCMI is predictive of medical and
      surgical risk, patients who sustained a major complication now carry a greater
      likelihood of adverse outcomes with future interventions, including subsequent
      spine surgery. Although PRO scores are a key metric, they fail to adequately
      reflect the potential long-term impact of major perioperative complications.

PMID- 28753066
TI  - A Single Exposure to Low- or High-LET Radiation Induces Persistent Genomic Damage
      in Mouse Epithelial Cells In Vitro and in Lung Tissue.
AB  - Exposures to low- and high-linear energy transfer (LET) radiation induce
      clustered damage in DNA that is difficult to repair. These lesions are manifested
      as DNA-associated foci positive for DNA repair proteins and have been shown to
      persist in vitro and in vivo for days in several cell types and tissues in
      response to low-LET radiation. Although in some experimental conditions these
      residual foci have been linked with genomic instability and chromosomal
      aberrations, it remains poorly understood what type of damage they represent.
      Because high-LET radiation induces complex DNA lesions more efficiently than low
      LET radiation, we compared the efficacy of several heavy ions (oxygen, silicon
      and iron) in a range (17 , 70 and 175 keV/MUm, respectively) of LET and X rays at
      a 1 Gy dose. Persistent genomic damage was measured by gamma-H2AX-53BP1-positive
      residual foci and micronucleus levels during the first three days and up to a
      week after in vitro and in vivo irradiation in lung cells and tissue. We
      demonstrate that in an in vitro irradiated mouse bronchial epithelial cell line,
      the expression of residual foci is readily detectable at 24 h with levels
      declining in the following 72 h postirradiation, but still persisting elevated
      over background at day 7. At this time, foci numbers are low but significant and
      proportional to the dose and quality of the radiation. The expression of residual
      foci in vitro was mirrored by increased micronuclei generation measured in
      cytokinesis-blocked cells, indicating long-term, persistent effects of genomic
      damage in this cell type. We also tested the expression of residual foci in lung
      tissue of C57BL/6 mice that received whole-body X-ray or heavy-ion irradiation.
      We found that at day 7 postirradiation, Clara/Club cells, but not pro-SPC
      positive pneumocytes, contained a subpopulation of cells expressing gamma-H2AX
      53BP1-positive foci in a radiation quality-dependent manner. These findings
      suggest that in vivo persistent DNA repair foci reflect the initial genotoxic
      damage induced by radiation and a differential vulnerability among cells in the
      lung.

PMID- 28753067
TI  - A Randomized, Placebo-Controlled Phase 2 Trial of CNTO 6785 in Chronic
      Obstructive Pulmonary Disease.
AB  - Interleukin (IL)-17A may be an underlying factor in the pathophysiology of
      chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies
      have been used successfully in treating several immune-mediated inflammatory
      diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel
      group, proof-of-concept study is the first clinical study evaluating the efficacy
      and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with
      symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n =
      93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then
      Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the
      change from baseline in pre-bronchodilator percent-predicted forced expiratory
      volume in 1 second at Week 16. Samples were collected at all visits for
      pharmacokinetic (PK) evaluation, and standard safety assessments were performed.
      The mean difference in the primary efficacy endpoint between CNTO 6785 and
      placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy
      endpoints demonstrated clinically or statistically significant differences with
      CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major
      safety signals were detected. The most frequently reported treatment-emergent
      adverse events were infections and infestations; however, no notable differences
      were observed between CNTO 6785 and placebo in terms of rates of infections. PK
      results suggested that the steady state of serum CNTO 6785 concentration was
      reached within 16 weeks. These results suggest that IL-17A is unlikely to be a
      dominant driver in the pathology of, or a viable therapeutic target for, COPD.
      ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.

PMID- 28753068
TI  - A Qualitative Exploration of Multiple Perspectives on Transfer of Learning
      Between Classroom and Clinical Workplace.
AB  - : Phenomenon: Transfer of learning between classroom and workplace appears to be
      difficult. Various conceptions about learning in either the classroom or the
      workplace exist among stakeholders, yet little is known about their conceptions
      of the transfer of learning between both settings. This study explored
      stakeholders' conceptions about transfer of learning between classroom-based
      learning and workplace practice. APPROACH: Homogeneous focus groups with
      students, medical teachers, and workplace supervisors were conducted using a
      constructivist grounded theory approach. FINDINGS: The 54 participants'
      conceptions mainly related to their beliefs about who was responsible for (a)
      preparing for transfer of learning, (b) being at the workplace and connecting
      back to classroom-based learning, and (c) reflecting on transfer of learning and
      continuing the process. A continuum was recognized between those who held medical
      teachers/workplace supervisors responsible and those who held students
      responsible. Insights: There appears to be a variety of conceptions about who is
      responsible for enabling the transfer process. These conceptions may influence
      learning and instructional activities. Hence, it may be necessary to make these
      beliefs explicit in order to better align stakeholders' conceptions. To this end,
      the conceptual framework created in this study may be a useful tool.

PMID- 28753069
TI  - Door to Needle Time over Telestroke-A Comprehensive Stroke Center Experience.
AB  - BACKGROUND: The implementation of telestroke programs has allowed patients living
      in rural areas suffering from acute ischemic stroke to receive expert acute
      stroke consultation and intravenous Alteplase (tPA). The purpose of this study is
      to compare door to needle (DTN) time when tPA is administered at telestroke sites
      (spokes) through telestroke consultations compared to tPA administration at the
      comprehensive stroke center (hub). METHODS: Data on all patients who received
      intravenous tPA at the hub and spoke hospitals through a large telestroke program
      between May 2008 and December 2016 were collected. Baseline characteristics were
      compared between the two groups, and the percentage of patients meeting DTN
      guidelines was compared between the hub and spoke hospitals during the study
      period. Comparison of DTN before and after the implementation of a quality
      improvement project was performed. RESULTS: A total of 1,665 patients received
      tPA at either the spoke (n = 1,323) or the hub (n = 342) during the study period.
      Baseline characteristics were comparable in both treatment groups. Before the
      intervention, DTN time <60 min was achieved in 88% of the hub patients versus 38%
      of the spoke patients. This difference between the two groups decreased by 35
      percentage points, controlling for year (p = 0.0018) after the interventions.
      CONCLUSION: Overall, DTN is longer at the spoke hospitals compared to the hub
      hospital. This can be improved by various interventions that target quality,
      training, education, and improving the comfort level of the staff at partner
      hospitals when treating acute stroke patients.

PMID- 28753070
TI  - Impact of Mucolytic Agents on COPD Exacerbations: A Pair-wise and Network Meta
      analysis.
AB  - Mucolytics are potentially useful for the management of chronic obstructive
      pulmonary disease (COPD), although there is conflicting advice on their use in
      different guideline documents. Furthermore, there is paucity of data comparing
      the efficacy of the different mucolytic agents in reducing the odds of COPD
      exacerbations. We performed pair-wise and network meta-analyses to evaluate the
      impact of mucoly-tics in COPD. Randomized clinical trials lasting at least 3
      months and investigating the effects of mucolytics on COPD exacerbations were
      identified from published studies and repository databases. Mucolytics
      significantly reduced the odds of exacerbation vs. placebo (11 studies analyzed:
      odds ratio (OR) 0.51, 95% confidence interval (CI) 0.39-0.67; p < 0.001). The
      most effective drugs were carbocysteine, erdosteine, and N-acetylcysteine 1,200
      mg/day (SUCRA 68.0-79.0%), whereas the OR was similar to placebo for ambroxol and
      N-acetylcysteine 600 mg/day. Only N-acetylcysteine 1,200 mg/day significantly
      protected against exacerbations vs. placebo (2 studies analyzed: OR 0.56, 95% CI
      0.35-0.92; p < 0.05; high quality of evidence). A signal of effectiveness was
      detected for carbocysteine (2 studies analyzed: OR 0.45, 95% CI 0.20-1.01; p >=
      0.05; moderate quality of evidence). Specific differences in study designs and
      patient-related characteristics, such as history of exacerbations and ethnicity,
      were potential effect modifiers for our statistical models, whereas neither
      respiratory function nor the use of corticosteroids influenced the analysis. This
      meta-analysis demonstrates that mucolytics are useful in preventing COPD
      exacerbations as maintenance add-on therapy to patients with frequent
      exacerbations. The effectiveness of mucolytics is independent of the severity of
      airway obstruction and the use of inhaled corticosteroids.

PMID- 28753071
TI  - Case Selection for Laparoscopic Reversal of Hartmann's Procedure.
AB  - BACKGROUND: Laparoscopic reversal of Hartmann's procedure offers reduced
      morbidity compared with open surgery while improving reversal rates. However, it
      is one of the most technically challenging operations in minimally invasive
      colorectal surgery, with further < 20% of the reversal procedures being attempted
      laparoscopically. Complications related to late conversion to open surgery may
      suggest a selective use of the laparoscopic approach for Hartmann's reversal in a
      subgroup of patients: The aim of this study is to systematically investigate the
      literature to identify the ideal case for a laparoscopic approach. MATERIALS AND
      METHODS: Data were extracted from a systematic review of the literature of
      Medline, Scopus, Web of Science, Embase, and the Cochrane Central Register of
      controlled trials. Subgroup analysis to identify suitable patients for
      laparoscopic surgery included age at surgery, body mass index, American Society
      of Anesthesiologists status, indication for the index Hartmann's procedure (HP),
      interval time to reversal from the index HP, conversion to open surgery, and
      temporary ileostomy rate. RESULTS: A total of 862 patients were included, with
      403 cases performed laparoscopically. Conversion to open surgery occurred in 65
      patients (mean 16.1%). The indication for the HP showed a trend toward more
      benign patients included in the laparoscopic group, and the interval time between
      the index Hartmann's procedure and its reversal was significantly shorter in the
      laparoscopic group with a trend toward a higher rate of temporary ileostomy in
      patients undergoing an open procedure. CONCLUSIONS: Patients' selection can
      explain these differences, with more complex disease operated via an open
      approach. Nevertheless, future studies are needed to demonstrate an increasing
      number of reversals attempted laparoscopically in high-volume centers.

PMID- 28753072
TI  - Beliefs about age-related changes in physical functioning across the adult life
      span and their relationship with physical activity levels of older adults.
AB  - Physical activity declines across the adult life span despite the well
      established links between physical activity and health-related, psychological,
      cognitive, and social benefits. We contrasted the beliefs young and older adults
      hold about how aging affects both physical abilities and physical activity and
      determined whether older adults' beliefs about physical aging relate to their
      engagement in physical activity. Using visual rating scales, 56 young and 49
      community-dwelling older adults indicated the extent to which a typical woman or
      typical man aged 20-90 possesses six different physical abilities and engages in
      three different types of physical activity. Stereotypes of physical aging were
      ability- and activity-specific, and older adults endorsed more positive views
      than their younger peers. Stereotypical beliefs predicted older adults'
      engagement in moderate-intensity activity. This study offers intriguing avenues
      for future research and suggests that better understanding physical aging
      stereotypes may contribute toward designing interventions that promote lifelong
      physical activity.

PMID- 28753073
TI  - Evaluating the Association of Common Variants of the SLC44A4 Gene with Ulcerative
      Colitis Susceptibility in the Han Chinese Population.
AB  - OBJECTIVE: The SLC44A4 gene was recently reported to be associated with
      ulcerative colitis (UC) susceptibility in the Indian and Japanese populations.
      The aim of our study was to investigate the association of common variants within
      the SLC44A4 gene and the susceptibility to UC among the Han Chinese. METHODS: We
      examined 16 tag single nucleotide polymorphisms (SNPs) within the SLC44A4 gene in
      a Han Chinese population that consisted of 311 UC patients and 675 healthy
      controls; both SNP and haplotypic association analyses were performed. RESULTS:
      We found that rs2736428 was significantly associated with UC risk (allelic p =
      0.0004), and the CT and TT genotypes of rs2736428 had a higher distribution
      compared with the CC genotypes (genotypic p = 0.001), suggesting that the T
      allele was a risk allele (odds ratio = 1.45, 95% confidence interval = 1.18
      1.78). Moreover, one haplotype block that included rs2736428 was found to be
      strongly associated with UC risk as well (global p < 0.001). CONCLUSION: Our
      results provide further supportive evidence for an important role of the SLC44A4
      gene in the pathogenesis of UC.

PMID- 28753074
TI  - Acute pneumonitis associated with nickel carbonyl exposure in the workplace.
AB  - BACKGROUND: We describe the clinical course of one industrial technician
      occupationally exposed to nickel carbonyl (NiC). CASE REPORT: A 50-year-old male
      industrial technician presented with complaints of nausea, myalgia, and cough to
      a local clinic after suspected occupational exposure to nickel carbonyl. He has
      no history of lung disease or smoking. His initial urine nickel concentration was
      692 ug/L. He had infiltrates on the initial chest X-ray (CXR) and an oxygen
      saturation (O2) of 97% on room air. The patient was started on disulfiram 1 g by
      mouth (PO), 500 mg six hours after the first dose, then 250 mg twice daily for
      five days with prednisone 60 mg by mouth for five days. He presented 48 hours
      later with worsening respiratory symptoms. His O2 saturation decreased to 85%
      despite two days of oral steroids, and he was admitted to a hospital. He received
      prednisone 60 mg/day PO, 4 L nasal O2, and disulfiram 500 mg twice daily. He was
      discharged on day 7 post-exposure with disulfiram and prednisone. Case
      discussions: NiC is a severe respiratory irritant. Disulfiram was used off-label
      and was based on an established company protocol. CONCLUSIONS: Inhalation
      exposure to NiC resulted in a delayed respiratory dysfunction which responded to
      disulfiram treatment.

PMID- 28753075
TI  - Self-Determination Theory and Risk Behavior in a Collectivistic Society:
      Preventing Reckless Driving in Urban Nepal.
AB  - Traffic road accidents are one of the leading causes of mortality in Nepal and
      around the world. Drivers in Nepal are not adequately educated about road safety
      rules. Road conditions are chaotic as traffic regulations are also not strictly
      enforced. Public safety campaigns may be able to alter drivers' attitudes and
      behaviors; however, little is known about which persuasive strategies may be most
      effective. Drawing on self-determination theory and the Health Belief Model, the
      current study used a post-only experimental design to test the impact of a short
      video message. The video included collective vs. individual appeals, and messages
      emphasizing one's ability to make the right choice (autonomy support) vs.
      directive language. Participants were Nepali college students (mean age 20, N =
      199). Using structural equation modeling, the study found that directive messages
      rather than autonomy support influenced an individual seeing value in the
      recommended behavior (identified regulation), which in turn influenced perceived
      susceptibility, perceived severity, and behavioral intention. The study also
      proposed a behavior change model by incorporating the stage of identification
      with the message upon exposure. This model aims to expand the model proposed by
      the Health Belief Model, to include a stage of value identification before cues
      to action influence perception of threat. Further implications are discussed.

PMID- 28753076
TI  - The burden of psychosocial morbidity related to cancer: patient and family
      issues.
AB  - With cancer incidence increasing over time, attention to the burden of related
      psychiatric and psychosocial consequences of the disease and treatment is a major
      topic for both cancer patients and their caregivers. Among cancer patients,
      psychiatric (e.g. adjustment, anxiety, depressive disorders) and neuropsychiatric
      disorders (e.g. cognitive disorders secondary to treatment, delirium) have been
      shown to affect an average of 30-35% patients, with differences according to
      stage and type of cancer. Also other psychosocial syndromes (e.g. demoralization,
      health anxiety, irritable mood) not taken into account in usual nosological
      systems should be considered for their impact on the patient's quality-of-life.
      Also, it has been repeatedly reported that psychological distress reverberates
      substantially throughout the nuclear family, and that a family approach is
      necessary in cancer care, with the caregiver-patient dyad as a unit to be the
      focus and direction of assessment and intervention. In this review the most
      significant psychosocial disorders causing burden for cancer patients and their
      caregivers are examined, and the main methods of assessment for more proper
      referral and treatment are summarized.

PMID- 28753077
TI  - Low dose cyclosporine A in the treatment of resistant proliferative lupus
      nephritis.
AB  - OBJECTIVE: This study aimed to evaluate long-term efficacy of low dose
      cyclosporine A (CsA) in the treatment of resistant proliferative lupus nephritis.
      METHODS: In this retrospective study, patients with biopsy proven proliferative
      lupus nephritis who were unresponsive to combination therapy with steroid plus
      mycophenolate mofetil (MMF) or cyclophosphamide (CYC) and had been treated with
      CsA were included. Efficacy monitoring was based on the systemic lupus
      erythematosus (SLE) disease activity index, dose of prednisolone, serum
      complement, anti-double stranded DNA (anti-dsDNA) titration, urine analysis,
      proteinuria, creatinine clearance, remission of the renal disease, renal survival
      and involvement of other organs. RESULTS: This study included 27 consecutive
      patients (22 females, 5 males) with resistant proliferative lupus nephritis. Mean
      duration of follow up and treatment with CsA were 40.7 +/- 24.9 and 35.2 +/- 19.1
      months, respectively. Complete and partial renal remission occurred in 66.9% and
      25.7% patients, respectively. Creatinine clearance was stable, proteinuria and
      anti-dsDNA titer decreased, and C3 and C4 increased significantly during the
      treatment with CsA. Severe complications such as death, dialysis, kidney
      transplantation and severe infection did not occur in the studied patients during
      the follow-up period. CONCLUSIONS: Low-dose CsA could induce renal remission and
      ameliorate the SLE disease activity in patients with resistant proliferative
      lupus nephritis and it would be a safe drug for treatment of these patients.

PMID- 28753078
TI  - Which is more effective for pain relief during fractionated carbon dioxide laser
      treatment: EMLA cream or forced cold air anesthesia?
AB  - BACKGROUND AND AIM: The aim of this study was to compare the effectiveness of a
      eutectic mixture of local anesthetic (EMLA) cream and forced cold air anesthesia
      (FCAA) on pain control during ablative fractionated carbon dioxide (CO2) laser
      treatment. METHODS: Fifteen volunteers participated in this prospective,
      controlled, split-face clinical study. EMLA cream was applied 60 minutes before
      the laser procedure on half of the face, and FCAA was performed on each subunit
      of the other half of the face. The laser procedure was performed on each half of
      the face. Patients rated their pain during the procedure using a pain scale
      scored from 0-10. Both doctor and nurse rated patient discomfort during the
      procedure using a scale scored from 0-10. The pain scores associated with both
      EMLA and FCAA sides of the face were compared statistically. RESULTS: Patient
      pain scores and discomfort scores detected by doctor and nurse were not
      statistically different between EMLA and FCAA. There was no statistically
      significant difference between males and females. CONCLUSION: Instead of using
      EMLA, FCAA-which can be applied in a shorter time-may be a cost-effective,
      simple, and safe local anesthesia method used in the ablative fractionated CO2
      laser procedure.

PMID- 28753079
TI  - Applying a Positive Youth Development Perspective to Observation of Bereavement
      Camps for Children and Adolescents.
AB  - A positive youth development perspective focuses on recognizing psychosocial
      strengths and providing social environments that contribute to the development of
      these in children and adolescents. Bereavement camps can provide such an
      environment as they help children cope with the death of someone close. The
      purpose of this study was to observe bereavement camps through the lens of
      positive youth development to determine the applicability of the eight features
      of positive developmental settings for describing bereavement camps (safety,
      appropriate structure, supportive relationships, opportunities to belong,
      positive norms, support for efficacy, skill building opportunities, integration
      of family and community). Observational notes were recorded by researchers during
      on-site visits to three different weekend bereavement camps. Results identified
      how each element of positive developmental settings was exemplified in either
      typical camp activities or bereavement-focused activities. For example, assigning
      campers to cabin groups based on age and gender provided opportunities to belong,
      and giving campers a comfort object and a big buddy provided supportive
      relationships. Findings were used to create a positive developmental settings
      observation checklist for use by bereavement camp practitioners to assess the
      extent to which each camp provides the requisite elements for promoting positive
      youth development.

PMID- 28753080
TI  - Websites Related to Volume 31, Issue 3.

PMID- 28753081
TI  - 'Even though a man takes the major role, he has no right to abuse': future male
      leaders' views on gender-based violence in Sri Lanka.
AB  - BACKGROUND: Distinct gender roles influence gender inequality and build the
      foundation for gender-based violence. Violence against women is a major public
      health problem in all societies, and a violation of human rights. Prevalence
      surveys on gender-based violence have been published from Sri Lanka, but
      qualitative studies on men's perceptions are lacking. OBJECTIVES: The aim of this
      study was to explore young educated Sri Lankan men's perceptions of violence
      against women. METHODS: Seven focus-group discussions were held. Men at the end
      of their university studies were purposefully selected. A topic guide was used,
      covering various scenarios of violence against women. Qualitative content
      analysis was carried out. RESULTS: Four categories were developed through the
      analytic process: fixed gender roles - patriarchal values are accepted in
      society, female mobility control, and slowly changing attitudes; violence not
      accepted but still exists - sexual harassment exists everywhere, different laws
      for different people, female tolerance of violence, and men's right to punish;
      multiple factors cause violence - alcohol, violent behavior is inherited,
      violence culturally accepted, low education, and lack of communication; and
      prevention of violence against women - both parents must engage and socialize
      girls and boys equally, life skills education, premarital counselling, working
      places value clarification, and more women in politics and boards are suggested.
      CONCLUSIONS: Medical and management students, possible future male leaders of the
      country, have suggestions of prevention strategies in life skills to reduce
      gender-based violence and to increase knowledge of health consequences with the
      aim of changing attitudes.

PMID- 28753082
TI  - Improvements in Kinematic Performance After Home-Based Bimanual Intensive
      Training for Children with Unilateral Cerebral Palsy.
AB  - AIMS: To evaluate the effects of home-based intensive bimanual training for
      children with unilateral spastic cerebral palsy (USCP) on bimanual coordination
      using 3-D kinematic analyses. METHODS: Seven children with USCP (aged 29-54
      months, MACS level: I-III) received 90 hours (2 hrs/day, 5days/week for 9 weeks)
      of Home Hand-Arm Bimanual Intensive Training (H-HABIT) provided by trained
      caregivers. A bimanual drawer-opening task was evaluated with eight infrared
      cameras using VICON workstation4.6 before and after training to assess
      improvements in bimanual coordination. RESULTS: H-HABIT training significantly
      decreased the time between one hand opening the drawer and the other hand
      manipulating its contents (p < 0.05) and increased the percentage of time when
      both hands were moving simultaneously (p = 0.001), which are indicators of
      improved temporal bimanual coordination. In addition, participants demonstrated a
      26% decrease in trunk displacement (p < 0.05), a 30% increase in upper arm joint
      excursion (p < 0.01), and a 25% increase in elbow extension (p < 0.05) for the
      affected side. All the improvements were maintained at 6-month posttest.
      CONCLUSIONS: H-HABIT improved not only temporal, but also quality of movement
      during a bimanual task for seven children with USCP. Thus, H-HABIT could be an
      alternative or adjunctive treatment for children with USCP.

PMID- 28753083
TI  - Examining the perceived impact of an ethics workshop on interprofessional values
      and teamwork.
AB  - Interprofessional education (IPE) is a vital component of healthcare education
      yet challenges to implementation persist. This study aimed to evaluate the
      perceived impact of an ethics-based IPE workshop designed for professional phase
      healthcare students enrolled in athletic training, health management systems,
      occupational therapy, physical therapy, physician assistant studies, and speech
      language pathology programmes at one university. A pre/post-test cohort study was
      conducted to evaluate the impact of the workshop on interprofessional values and
      teamwork. Findings from the 61 students who completed both pre- and post
      programme evaluation surveys suggest that the ethics-based workshop was
      successful in improving perceived confidence as related to the workshop
      objectives and strengthened positive perceptions of IPE as evaluated by the
      Student Perceptions of Interprofessional Clinical Education-Revised (SPICE-R).
      Analysis of responses to open-ended reflection questions after the workshop
      suggest that student participants perceived changes in understanding related to
      multiple areas of IPE. These results suggest that an ethics-based workshop using
      case-based collaborative pedagogy may be an effective mechanism for delivery of
      IPE-oriented information resulting in greater student confidence and
      understanding of IPE competencies.

PMID- 28753084
TI  - Development and Implementation of a School-Wide Institute for Excellence in
      Education to Enable Educational Scholarship by Medical School Faculty.
AB  - PROBLEM: Educational scholarship is an important component for faculty at
      Academic Medical Centers, especially those with single-track promotion systems.
      Yet, faculty may lack the skills and mentorship needed to successfully complete
      projects. In addition, many educators feel undervalued. INTERVENTION: To
      reinvigorate our school's educational mission, the Institute for Excellence in
      Education (IEE) was created. Here we focus on one of the IEE's strategic goals,
      that of inspiring and supporting educational research, scholarship, and
      innovation. CONTEXT: Using the 6-step curriculum development process as a
      framework, we describe the development and outcomes of IEE programs aimed at
      enabling educational scholarship at the Johns Hopkins University School of
      Medicine. OUTCOME: Four significant programs that focused on educational
      scholarship were developed and implemented: (a) an annual conference, (b) a
      Faculty Education Scholars' Program, (c) "Shark Tank" small-grant program, and
      (d) Residency Redesign Challenge grants. A diverse group of primarily junior
      faculty engaged in these programs with strong mentorship, successfully completing
      and disseminating projects. Faculty members have been able to clarify their
      personal goals and develop a greater sense of self-efficacy for their desired
      paths in teaching and educational research. LESSONS LEARNED: Faculty require
      programs and resources for educational scholarship and career development,
      focused on skills building in methodology, assessment, and statistical analysis.
      Mentoring and the time to work on projects are critical. Key to the IEE's success
      in maintaining and building programs has been ongoing needs assessment of faculty
      and learners and a strong partnership with our school's fund-raising staff. The
      IEE will next try to expand opportunities by adding additional mentoring capacity
      and further devilment of our small-grants programs.

PMID- 28753085
TI  - Perceptions of Food Advertising and Association With Consumption of Energy-Dense
      Nutrient-Poor Foods Among Adolescents in the United States: Results From a
      National Survey.
AB  - The advertising and marketing of energy-dense, nutrient-poor (EDNP) food and
      drink has been cited as one contributor to unhealthy eating behaviors in
      adolescents. The present study examines perceptions about and trust in food
      advertising and their association with consumption of EDNP foods and drinks among
      adolescents in the United States. Data (n = 1,384) come from the U.S. National
      Cancer Institute's Family Life, Activity, Sun, Health, and Eating Survey. One way
      ANOVAs were conducted to assess differences between population subgroups in
      advertising perceptions. Bivariate and multivariable linear regression models
      were used to examine the associations between perceptions toward and trust in
      food advertising and consumption of EDNP foods and drinks, controlling for
      sociodemographic factors. Results show that there are significant differences
      between racial/ethnic groups on advertising perceptions (F = 16.32, p = < .0001).
      As positive perceptions toward food advertising increase among adolescents, there
      is an associated increase in daily frequency of consumption of EDNP foods and
      drinks (beta = 0.10, p < .01). Similarly, the more adolescents agreed that they
      trusted food advertising, the higher the reported daily frequency of EDNP food
      and drink consumption (beta = 0.08, p = .01). Targeting perceptions about food
      advertising may be a worthy intervention strategy to reduce the impact of food
      marketing and the consumption of heavily advertised EDNP foods and drinks among
      adolescents.

PMID- 28753087
TI  - Clarifying the meaning of attachment disorganization.

PMID- 28753086
TI  - Gender and Age Differences in Sleep Problems in Children: Person-Oriented
      Approach With Multigroup Analysis.
AB  - OBJECTIVE/BACKGROUND: This study aimed to identify subtypes of sleep problems in
      children and to examine whether these patterns differed between gender and age
      groups. PARTICIPANTS: There were 3,052 children (951 elementary school boys, 943
      elementary school girls, 603 junior high school boys, and 555 junior high school
      girls) aged 7-16 years from two school-based epidemiological samples. METHODS:
      Sleep problems were measured by the Sleep Habit Questionnaire based on parent
      reports. RESULTS: Using the latent class modeling, a person-oriented approach,
      with a multigroup analysis, we identified four classes of sleep problems:
      moderate to high sleep problems (1.1%-3.1%), sleep-related breathing problems and
      parasomnias dominant (14.9%-21.1%), insomnias dominant and parasomnias (1.0%
      3.1%), and no or low sleep problems (74.7%-81.4%), with varied prevalence rates
      of sleep problems across gender and age groups. CONCLUSIONS: This study
      identified four classes of sleep problems across gender and age groups but with
      different prevalence rates of sleep problems, suggesting the complex interaction
      of gender and age in the subtypes of sleep problems. The gender- and age-specific
      interventions for sleep problems are suggested. Future studies are warranted to
      replicate these classes and to identify associated factors with each class.

PMID- 28753088
TI  - Histologic analyses on the response of the skin to 1,927-nm fractional thulium
      fiber laser treatment.
AB  - BACKGROUND: The histologic responses to varied parameters of 1,927-nm fractional
      thulium fiber laser treatment have not yet been sufficiently elucidated.
      OBJECTIVE: This study sought to evaluate histologic changes immediately after
      1,927-nm fractional thulium fiber laser session at various parameters. METHODS:
      The dorsal skin of Yucatan mini-pig was treated with 1,927-nm fractional thulium
      fiber laser at varied parameters, with or without skin drying. The immediate
      histologic changes were evaluated to determine the effects of varying laser
      parameters on the width and the depth of treated zones. RESULTS: The increase in
      the level of pulse energy widened the area of epidermal changes in the low power
      level, but increased the dermal penetration depth in the high power level. As the
      pulse energy level increased, the increase in the power level under the given
      pulse energy level more evidently made dermal penetration deeper and the
      treatment area smaller. Skin drying did not show significant effects on epidermal
      changes, but evidently increased the depth of dermal denaturation under both high
      and low levels of pulse energy. CONCLUSION: These results may provide important
      information to establish treatment parameters of the 1,927-nm fractional thulium
      fiber laser for various skin conditions.

PMID- 28753089
TI  - Emerging criteria for the low-coherence cannot classify category.
AB  - As suggested by Main et al., to respond to the need for an adaptation of the
      existing Adult Attachment Interview (AAI) coding system, especially regarding the
      application to nonnormative samples, this study presents additional criteria that
      characterize the low-coherence cannot classify (CC) category. Three AAIs were
      selected from a sample of parents of maltreated children. All transcripts
      indicated a very low coherence, with no evidence of contradictory insecure
      discourse strategies. Moreover, global category descriptors were identified,
      together with specific indices of discourse characteristics and features that
      highlight the breakdown in reasoning and discourse experienced by the speakers.
      The aim of the study is to illustrate new criteria to identify and rate a low
      coherence CC profile toward the operationalization of this pervasively
      unintegrated state of mind. Through the definition of additional criteria for low
      coherence CC category, our study helps the AAI and its coding system be more
      flexible and effective when dealing with clinical samples.

PMID- 28753090
TI  - Brainstem angiocentric glioma: report of 2 cases.
AB  - Angiocentric glioma is a rare tumor that was recognized by the WHO Classification
      of Tumours of the Central Nervous System as a distinct clinicopathological entity
      in 2007. Since this initial description, the vast majority of cases of
      angiocentric glioma reported in the literature have involved tumors of the
      cerebral hemispheres. To date, only 1 case of angiocentric glioma arising from
      the posterior midbrain has been reported. The authors present the cases of 2
      pediatric patients who were found to have brainstem angiocentric gliomas. The
      clinical course, radiological and pathological features, treatment, and follow-up
      are described. The first case is one of a 5-year-old girl who presented with
      double vision, headache, and nausea and was found to have a midbrain lesion with
      pathological features consistent with angiocentric glioma. She was treated with
      resection and endoscopic third ventriculostomy (ETV), followed by close
      observation and serial neuroimaging. The second case is one of a 6-year-old boy
      who presented with progressive mouth drooping and problems with balance. He was
      found to have a pontine lesion with pathological features consistent with
      angiocentric glioma. This patient was treated with ETV, followed by close
      observation and serial neuroimaging. This report includes 6 and 1.5 years of
      follow-up of the patients, respectively. While there are limited data regarding
      the prognosis or long-term management of patients with brainstem angiocentric
      gliomas, the cases described in this report suggest an indolent course for this
      tumor, similar to the course of angiocentric gliomas located in the cerebral
      hemispheres.

PMID- 28753091
TI  - Neuroendoscopic surgery in children: does age at intervention influence safety
      and efficacy? A single-center experience.
AB  - OBJECTIVE The aim of this study was to review the safety of pediatric
      intraventricular endoscopy across separate age groups and to determine whether
      intraventricular endoscopy is associated with an increased risk of complications
      or reduced efficacy in infants younger than 1 year. METHODS In this retrospective
      cohort study, 286 pediatric patients younger than 17 years underwent
      intraventricular endoscopy at Great Ormond Street Hospital between December 2005
      and December 2014. The primary diagnosis, procedure, and complications were
      recorded. RESULTS Neuroendoscopic surgery was performed in 286 pediatric patients
      (51 neonates 0-6 months [Group 1]; 37 infants 6-12 months [Group 2]; 75 patients
      1-5 years [Group 3]; 54 patients 5-10 years [Group 4]; and 69 patients >= 10
      years [Group 5]; male/female ratio 173:113). The most common procedures included
      endoscopic third ventriculostomy (ETV) in 159 patients and endoscopic
      fenestration of intracranial cysts in 64 patients. A total of 348 consecutive
      neuroendoscopic procedures were undertaken. Nine different complications were
      identified, of which postoperative seizures (1.7%), CSF leak (3.1%), CSF
      infection (2.4%), and intracranial hemorrhage (1.7%) were the most common.
      Specifically, no significant difference in complication rate (11.9%) or infection
      rate (2.4%) was observed among age groups (p = 0.40 and p = 0.91, respectively).
      In addition, there were no perioperative deaths; 30-day mortality was 1.1%. After
      neuroendoscopy for CSF diversion (n = 227), a significantly higher rate of shunt
      insertion was observed in the youngest group (Group 1, 63.0%) when compared with
      older groups (Group 2, 46.4%; Group 3, 26.3%; Group 4, 38.6%; and Group 5, 30.8%;
      p = 0.03). Similarly, for patients who underwent ETV as their initial
      neuroendoscopic procedure or in combination with additional surgical
      interventions (n = 171), a significantly higher rate of shunt insertion was also
      observed within young infants (Group 1, 67.9%; Group 2, 47.6%; Group 3, 19.6%;
      Group 4, 27.3%; and Group 5, 23.3%; p = 0.003). CONCLUSIONS Intraventricular
      endoscopy is a safe neurosurgical intervention in pediatric patients of all ages,
      although it might be associated with increased shunt rates after endoscopic
      surgery, specifically ETV, in younger infants.

PMID- 28753092
TI  - Effect of higher implant density on curve correction in dystrophic thoracic
      scoliosis secondary to neurofibromatosis Type 1.
AB  - OBJECTIVE The aim of this study was to investigate how implant density affects
      radiographic results and clinical outcomes in patients with dystrophic scoliosis
      secondary to neurofibromatosis Type 1 (NF1). METHODS A total of 41 patients with
      dystrophic scoliosis secondary to NF1 who underwent 1-stage posterior correction
      between June 2011 and December 2013 were included. General information about
      patients was recorded, as were preoperative and postoperative scores from
      Scoliosis Research Society (SRS)-22 questionnaires. Pearson correlation analysis
      was used to analyze the associations among implant density, coronal Cobb angle
      correction rate and correction loss at last follow-up, change of sagittal curve,
      and apical vertebral translation. Patients were then divided into 2 groups: those
      with low-density and those with high-density implants. Independent-sample t-tests
      were used to compare demographic data, radiographic findings, and clinical
      outcomes before surgery and at last follow-up between the groups. RESULTS
      Significant correlations were found between the implant density and the coronal
      correction rate of the main curve (r = 0.505, p < 0.01) and the coronal
      correction loss at final follow-up (r = -0.379, p = 0.015). There was no
      significant correlation between implant density and change of sagittal profile (p
      = 0.662) or apical vertebral translation (p = 0.062). The SRS-22 scores improved
      in the appearance, activity, and mental health domains within both groups, but
      there was no difference between the groups in any of the SRS-22 domains at final
      follow-up (p > 0.05 for all). CONCLUSIONS Although no significant differences
      between the high- and low-density groups were found in any of the SRS-22 domains
      at final follow-up, higher implant density was correlated with superior coronal
      correction and less postoperative correction loss in patients with dystrophic NF1
      associated scoliosis.

PMID- 28753094
TI  - Eyes on New Product Development.

PMID- 28753093
TI  - Synthesis and carbonic anhydrase I, II, VII, and IX inhibition studies with a
      series of benzo[d]thiazole-5- and 6-sulfonamides.
AB  - A series of benzo[d]thiazole-5- and 6-sulfonamides has been synthesized and
      investigated for the inhibition of several human (h) carbonic anhydrase (CA, EC
      4.2.1.1) isoforms, using ethoxzolamide (EZA) as lead molecule. 2-Amino
      substituted, 2-acylamino- and halogenated (bromo-and iodo-derivatives at the
      heterocyclic ring) compounds led to several interesting inhibitors against the
      cytosolic hCA I, II and VII, as well as the transmembrane, tumor-associated hCA
      IX isoforms. Several subnanomolar/low nanomolar, isoform-selective sulfonamide
      inhibitors targeting hCA II, VII and IX were detected. The sharp structure
      activity relationship for CA inhibition with this small series of derivatives,
      with important changes of activity observed even after minor changes in the
      scaffold or at the 2-amino moiety, make this class of scarcely investigated
      sulfonamides of particular interest for further investigations.

PMID- 28753095
TI  - A scanner-based colorimetric mercuric ion detection using Tween-20-stabilized
      AuNPs solution in 96-well plates.
AB  - This paper reports the development of a sensitive, high-throughput colorimetric
      method for the detection of trace mercuric ions (Hg2+). The method is based on
      the binding of the analyte to gold nanoparticles (AuNPs) modified with Tween-20.
      Tween-20 was used as a nonionic stabilizer to allow a good dispersion of AuNPs in
      solution. When mercuric ions were added to the solution, they replaced the Tween
      20 stabilizer on the surface of the AuNPs due to their stronger binding affinity.
      This caused the NPs to aggregate and the color of the solution to change from red
      to blue. The quantitative analysis of Hg2+ was achieved by plotting the Red Green
      Blue (RGB) values of the scanned images of the analyte samples in the AuNP
      solution against concentrations of Hg2+. Since the reaction was carried out in 96
      well plates, ninety-six samples were analyzed simultaneously, reducing the cost
      and time of analysis. The experimental parameters optimized were the
      concentrations of Tween-20 and NaCl, the reactants ratio, and the incubation
      time. Under the optimum conditions, the calibration plot of the assay was linear
      over an Hg2+ concentration range of 0.10-2.00 mg L-1, and the detection limit was
      0.050 mg L-1 (S/N  =  3). The selectivity of the technique was high with no
      significant colorimetric responses to the presence of 100-fold excesses of other
      metal ions. Quantification was validated with Hg2+ standard solutions and spiked
      tap and waste water samples, and the accuracy of the technique was confirmed. The
      developed technique is simple and cost effective because it requires no
      complicated instruments, yet the results demonstrate it to be a very powerful
      technique with the potential to be developed for on-site mercury detection.

PMID- 28753096
TI  - Conservative treatment of patients with thromboangiitis obliterans or cannabis
      associated arteritis presenting with critical lower limb ischaemia.
AB  - BACKGROUND: Proper management of patients with thromboangiitis obliterans (TAO)
      or cannabis-associated arteritis (CAA), presenting with critical lower limb
      ischaemia (CLI) remains controversial, and data are limited. PATIENTS AND
      METHODS: Patients with TAO or CAA presenting with CLI between 2011 and 2016 were
      retrospectively evaluated. Patients requiring primary intervention were excluded.
      Conservative treatment included: (a) weight-adjusted bemiparin plus six hours/day
      intravenous iloprost for 28 days, (b) aspirin (100 mg/day) plus cilostazol (100
      mg twice/day) after discharge, and (c) strict recommendations/monitoring for
      smoking cessation. Main outcomes included symptom recession, ankle-brachial index
      (ABI) improvement, and healing of lesions at the time of discharge as well as
      amputation, revascularization, and abstinence rate during follow-up. RESULTS:
      Overall, 23 patients (TAO: 15; CAA: 8) were included within six years, none of
      the patients reported any other factor than smoking. All patients presented with
      rest pain and 12 patients with ulcer or necrotic lesions. Mean ABI measurement at
      presentation was 0.46 +/- 0.2, after 28 days of treatment, all patients showed
      improvement regarding clinical picture and ABI measurement (0.54 +/- 0.1; p <
      0.05). During follow-up, only three patients underwent bypass surgery and two
      patients underwent major amputation, although the smoking abstinence rate was
      very low (13 %). CONCLUSIONS: Intravenous iloprost plus bemiparin for 28 days
      together with per os aspirin plus cilostazol seem to produce promising results in
      patients with TAO/CAA, treated for CLI, even with a low smoking abstinence rate.
      However, larger series are needed to further evaluate inter-group differences and
      potential prognostic factors.

PMID- 28753097
TI  - Mometasone furoate in the treatment of vulvar lichen sclerosus: could its
      formulation influence efficacy, tolerability and adherence to treatment?
AB  - PURPOSE: To assess the effectiveness, tolerability, and convenience of the cream
      formulation of mometasone furoate 0.1% (MMF) in the treatment of active vulvar
      lichen sclerosus (VLS) and to compare the cream with the ointment formulation.
      METHODS: The following efficacy parameters were assessed in 27 VLS patients
      treated with MMF cream for 12 weeks (group A): (i) response rate, (ii) percentage
      of patients achieving an improvement from baseline of >=75% in subjective and
      objective scores, and (iii) mean reduction in subjective and objective scores.
      These efficacy assessments, as well as those regarding safety and adherence, were
      compared with the assessments recorded among 37 VLS patients treated with MMF
      ointment (group B). RESULTS: 59.3% (group A) and 78.4% (group B) of patients were
      considered responders; 44.4% and 40.7% of patients in group A and 54.1% and 45.9%
      in group B achieved an improvement of at least 75% in subjective and objective
      scores, respectively. MMF ointment obtained a significantly higher improvement in
      symptom scores in comparison with the cream formulation. CONCLUSIONS: MMF in
      ointment formulation seems to be more effective in treating active VLS in
      comparison with MMF cream. Both formulations are well tolerated and there is no
      difference in patient adherence and satisfaction.

PMID- 28753098
TI  - Xenogenous Collagen Matrix and/or Enamel Matrix Derivative for Treatment of
      Localized Gingival Recessions: A Randomized Clinical Trial. Part II: Patient
      Reported Outcomes.
AB  - BACKGROUND: Gingival recession (GR) might be associated with patient discomfort
      due to cervical dentin hypersensitivity (CDH) and esthetic dissatisfaction. The
      aim is to evaluate the effect of root coverage procedure with a xenogenous
      collagen matrix (CM) and/or enamel matrix derivative (EMD) in combination with a
      coronally advanced flap (CAF) on CDH, esthetics, and oral health-related quality
      of life (OHRQoL) of patients with GR. METHODS: Sixty-eight participants with
      single Miller Class I/II GRs were treated with CAF (n = 17), CAF + CM (n = 17),
      CAF + EMD (n = 17), and CAF + CM + EMD (n = 17). CDH was assessed by evaporative
      stimuli using a visual analog scale (VAS) and a Schiff scale. Esthetics outcome
      was assessed with VAS and the Questionnaire of Oral Esthetic Satisfaction. Oral
      Health Impact Profile-14 (OHIP-14) questionnaire was used to assess OHRQoL. All
      parameters were evaluated at baseline and after 6 months. RESULTS: Intragroup
      analysis showed statistically significant reduction in CDH and esthetic
      dissatisfaction with no intergroup significant differences (P >0.05). The impact
      of oral health on QoL after 6 months was significant for CAF + CM, CAF + EMD, and
      CAF + CM + EMD (P <0.05). Total OHIP-14 score and psychologic discomfort,
      psychologic disability, social disability, and handicap dimensions showed
      negative correlation with esthetics. OHIP-14 physical pain dimension had positive
      correlation with CDH (P <0.05). OHIP-14 showed no correlation with percentage of
      root coverage, keratinized tissue width, or keratinized tissue thickness (P
      >0.05). CONCLUSION: Root coverage procedures improve patient OHRQoL by impacting
      on a wide range of dimensions, perceived after reduction of CDH and esthetic
      dissatisfaction of patients with GRs treated with CAF + CM, CAF + EMD, and CAF +
      CM + EMD.

PMID- 28753099
TI  - Receiver Operating Characteristic Curve-Based Prediction Model for Periodontal
      Disease Updated With the Calibrated Community Periodontal Index.
AB  - BACKGROUND: The accuracy of a prediction model for periodontal disease using the
      community periodontal index (CPI) has been undertaken by using an area under a
      receiver operating characteristics (AUROC) curve. How the uncalibrated CPI, as
      measured by general dentists trained by periodontists in a large epidemiologic
      study, and affects the performance in a prediction model, has not been researched
      yet. METHODS: A two-stage design was conducted by first proposing a validation
      study to calibrate CPI between a senior periodontal specialist and trained
      general dentists who measured CPIs in the main study of a nationwide survey. A
      Bayesian hierarchical logistic regression model was applied to estimate the non
      updated and updated clinical weights used for building up risk scores. How the
      calibrated CPI affected performance of the updated prediction model was
      quantified by comparing AUROC curves between the original and updated models.
      RESULTS: Estimates regarding calibration of CPI obtained from the validation
      study were 66% and 85% for sensitivity and specificity, respectively. After
      updating, clinical weights of each predictor were inflated, and the risk score
      for the highest risk category was elevated from 434 to 630. Such an update
      improved the AUROC performance of the two corresponding prediction models from
      62.6% (95% confidence interval [CI]: 61.7% to 63.6%) for the non-updated model to
      68.9% (95% CI: 68.0% to 69.6%) for the updated one, reaching a statistically
      significant difference (P <0.05). CONCLUSION: An improvement in the updated
      prediction model was demonstrated for periodontal disease as measured by the
      calibrated CPI derived from a large epidemiologic survey.

PMID- 28753100
TI  - Xenogenous Collagen Matrix and/or Enamel Matrix Derivative for Treatment of
      Localized Gingival Recessions: A Randomized Clinical Trial. Part I: Clinical
      Outcomes.
AB  - BACKGROUND: Considering xenogeneic collagen matrix (CM) and enamel matrix
      derivative (EMD) characteristics, it is suggested that their combination could
      promote superior clinical outcomes in root coverage procedures. Thus, the aim of
      this parallel, double-masked, dual-center, randomized clinical trial is to
      evaluate clinical outcomes after treatment of localized gingival recession (GR)
      by a coronally advanced flap (CAF) combined with CM and/or EMD. METHODS: Sixty
      eight patients presenting one Miller Class I or II GRs were randomly assigned to
      receive either CAF (n = 17); CAF + CM (n = 17); CAF + EMD (n = 17), or CAF + CM +
      EMD (n = 17). Recession height, probing depth, clinical attachment level, and
      keratinized tissue width and thickness were measured at baseline and 90 days and
      6 months after surgery. RESULTS: The obtained root coverage was 68.04% +/- 24.11%
      for CAF; 87.20% +/- 15.01% for CAF + CM; 88.77% +/- 20.66% for CAF + EMD; and
      91.59% +/- 11.08% for CAF + CM + EMD after 6 months. Groups that received
      biomaterials showed greater values (P <0.05). Complete root coverage (CRC) for
      CAF + EMD was 70.59%, significantly superior to CAF alone (23.53%); CAF + CM
      (52.94%), and CAF + CM + EMD (51.47%) (P <0.05). Keratinized tissue thickness
      gain was significant only in CM-treated groups (P <0.05). CONCLUSIONS: The three
      approaches are superior to CAF alone for root coverage. EMD provides highest
      levels of CRC; however, the addition of CM increases gingival thickness. The
      combination approach does not seem justified.

PMID- 28753101
TI  - Salivary and Serum Markers Related to Innate Immunity in Generalized Aggressive
      Periodontitis.
AB  - BACKGROUND: Host inflammatory and immune responses play an important role in
      aggressive periodontitis (AgP). Thus, this study aims to evaluate levels of the
      innate immunity-related markers calprotectin, colony-stimulating factor (CSF)-1,
      macrophage migration inhibitory factor (MIF), monokine induced by interferon
      gamma (MIG), and matrix metalloproteinase (MMP)-8 in serum and saliva from
      patients with generalized AgP and those with gingivitis or a healthy
      periodontium. METHODS: This study enrolled 40 individuals (17 males and 23
      females; mean age 33.30 +/- 9.31 years), 15 with generalized AgP, 15 with
      gingivitis, and 10 who were periodontally healthy. Full-mouth periodontal
      examinations were performed, and serum and saliva were collected. Levels of
      calprotectin, CSF-1, MIF, MIG, and MMP-8 were measured using enzyme-linked
      immunosorbent assays. RESULTS: In serum, mean levels of calprotectin were 2.06
      fold higher in patients with AgP than in healthy patients (P = 0.01). Serum
      levels of MMP-8 were significantly elevated in patients with AgP compared with
      both healthy patients and those with gingivitis, by 2.60-fold and 2.77-fold,
      respectively (P = 0.03 and P = 0.009, respectively). In saliva, levels of MMP-8
      were 5.66-fold higher in patients with AgP than in healthy patients (P = 0.02).
      CSF-1, MIF, and MIG levels in both serum and saliva did not differ significantly
      among the groups. CONCLUSIONS: Serum levels of calprotectin and MMP-8 are
      elevated in patients with AgP. MMP-8 levels are also increased in saliva from
      patients with AgP. These results support involvement of innate immune response in
      the pathogenesis of AgP.

PMID- 28753102
TI  - The Influence of a Bifidobacterium animalis Probiotic on Gingival Health: A
      Randomized Controlled Clinical Trial.
AB  - BACKGROUND: There is growing interest in the use of probiotics in periodontal
      therapy; however, until now, most research has focused on lactobacilli
      probiotics. The aim of this study is to evaluate the effect of 4-week use of
      yogurt supplemented with Bifidobacterium animalis subsp. lactis DN-173010 versus
      a placebo yogurt, followed by a 5-day non-brushing period. METHODS: Individuals
      were included in this single-mask, randomized, controlled study if probing depth
      (PD) was <=3 mm and attachment loss was <=2 mm. After professional prophylaxis,
      they were randomized into two groups receiving yogurt containing either placebo
      or B. animalis for 28 days, followed by a 5-day non-brushing period. Outcome
      measures were plaque index (PI), gingival index (GI), bleeding on probing (BOP),
      PD, gingival crevicular fluid (GCF) volume, and total amount and concentration of
      interleukin (IL)-1beta in GCF. These were measured at baseline, after 28 days of
      study product use, and subsequently after 5 days of plaque accumulation. RESULTS:
      Fifty-one patients were analyzed. No intergroup differences could be detected
      before and after intake of study products. However, after plaque accumulation,
      significantly better results for all parameters were seen in the probiotic group
      compared with the control group (P <0.001): lower PI and GI, less BOP, less
      increase in GCF volume, and lower IL-1beta total amount/concentration.
      CONCLUSION: The use of a probiotic yogurt supplemented with B. animalis can have
      a positive effect on plaque accumulation and gingival inflammatory parameters
      after refraining from oral hygiene practices.

PMID- 28753103
TI  - Effect of Alcohol Consumption on Clinical Attachment Loss Progression in an Urban
      Population From South Brazil: A 5-Year Longitudinal Study.
AB  - BACKGROUND: The aim of this study is to investigate the impact of alcohol
      consumption on clinical attachment loss (AL) progression over a period of 5
      years. METHODS: A multistage probability sampling strategy was used to draw a
      representative sample of the metropolitan area of Porto Alegre, Brazil. Five
      hundred thirty-two individuals (209 males and 293 females) aged 18 to 65 years at
      baseline with no medical history of diabetes and at least six teeth were included
      in this analysis. Full-mouth periodontal examinations with six sites per tooth
      were conducted at baseline and after 5 years. Alcohol consumption was assessed at
      baseline by asking participants about the usual number of drinks consumed in a
      week. Four categories of alcohol consumption were defined: 1) non-drinker; 2) <=1
      glass/week; 3) >1 glass/week and <=1 glass/day; and 4) >1 glass/day. Individuals
      showing at least two teeth with proximal (clinical AL) progression >=3 mm over 5
      years were classified as having disease progression. Multiple Poisson regression
      models adjusted for age, sex, smoking, socioeconomic status, and body mass index
      were used to estimate relative risks (RRs) and 95% confidence intervals (CIs).
      RESULTS: Overall, individuals who consumed >1 glass/day had 30% higher risk for
      clinical AL progression (RR = 1.30; 95% CI: 1.07 to 1.58) than non-drinkers.
      Among males, risk of clinical AL progression for individuals drinking >1
      glass/day was 34% higher than non-drinkers (RR = 1.34; 95% CI: 1.09 to 1.64).
      Never-smoker males drinking <=1 glass/week had significantly lower risk for
      clinical AL progression than non-drinkers (RR = 0.52; 95% CI: 0.30 to 0.89),
      whereas those drinking >1 glass/day had significantly higher risk (RR = 1.50; 95%
      CI: 1.08 to 1.99). Among females, no association between alcohol consumption and
      clinical AL progression was observed. CONCLUSIONS: Alcohol consumption increased
      the risk of clinical AL progression, and this effect was more pronounced in
      males. Low dosages (<=1.37 g of alcohol/day) of alcohol consumption may be
      beneficial to prevent periodontal disease progression in males. The impact of
      alcohol cessation initiatives on periodontal health should be evaluated.

PMID- 28753104
TI  - Porphyromonas gingivalis Suppresses Trophoblast Invasion by Soluble Factors.
AB  - BACKGROUND: Periodontitis is a common chronic inflammatory disorder that affects
      supporting tissues of the teeth. An increased risk of pregnancy complications has
      been reported in patients with periodontitis; however, its pathophysiology
      remains uncharacterized to date. In addition, Porphyromonas gingivalis (Pg) is
      detectable in a few placentae derived from diseased pregnancies. Thus, the aim of
      this study is to examine the roles of soluble factors produced by Pg on
      trophoblast invasion in vitro to clarify the remote effects of periodontitis on
      pregnancy outcomes. METHODS: The immortalized trophoblast cell line HTR-8/SVneo
      was cultured on plates or via hanging drop to evaluate viability, apoptosis, and
      morphology in the presence of the culture supernatant of Pg (PG-sup). Cells were
      plated on solubilized extracellular matrix rich membrane preparation plates to
      evaluate cell invasion. Morphologic changes were evaluated via stereomicroscopy,
      optical microscopy, and transmission electron microscopy. RESULTS: After 24 hours
      of culture, cell invasion was inhibited by PG-sup in a dose-dependent manner.
      Although cell viability and apoptotic counts were not affected by PG-sup,
      spheroid formation in hanging drop culture was inhibited. Spheroids became
      fragile and irregular in the presence of PG-sup. Transmission electron microscopy
      revealed shortened microvilli and increased intracellular spaces. CONCLUSIONS: PG
      sup inhibits trophoblast invasion and affects trophoblast morphology without
      direct cytotoxicity. These results indicate that Pg produces soluble factor(s)
      that suppress trophoblast invasion and subsequent vascular remodeling, which
      affect placental growth and fetal well-being. It is expected that the current
      findings will explain the increased prevalence of pregnancy complications in
      patients with periodontitis.

PMID- 28753107
TI  - Effect of Automobile Travel Time Between Patients' Homes and Ophthalmologists'
      Offices on Screening for Diabetic Retinopathy.
AB  - PURPOSE: The accessibility of ophthalmologists appears to influence the quality
      of screening for diabetic retinopathy (DR). The principal objective of this study
      was to analyze the effect of automobile travel time to the closest
      ophthalmologist on the time to DR screening. METHODS: This historical cohort
      study used reimbursement databases from the principal national health insurance
      fund. Patients were included if they had been reimbursed at least thrice for oral
      antidiabetic medications in the 12 months before the study start date. Patients
      were followed up from January 1, 2008, for 4 years. The expected event was a DR
      screening by an ocular fundus examination. The automobile travel time to the
      nearest ophthalmologist was calculated by the distance between communes,
      estimated by appropriate software. A Kaplan-Meier curve and a multivariate Cox
      model were used to model the effect of travel time on the time until DR
      screening. A sensitivity analysis of travel time described the results of the Cox
      model. RESULTS: At the start of 2008, 6,573 patients living in 328 different
      municipalities were included. The multivariate model found that patients living
      60 min or more away from an ophthalmologist had a lower instantaneous probability
      of DR screening than those living <30 min away (adjusted risk ratio = 0.82; 95%
      confidence interval 0.71-0.95; p = 0.009). The sensitivity analysis showed that
      this difference became significant at 35 min of travel time. CONCLUSION:
      Increased automobile travel time for patients with diabetes to the nearest
      ophthalmologist was associated with a longer time to DR screening.

PMID- 28753108
TI  - Reducing causes of inequity: policies focused on social determinants of health
      during generational transitions in Colombia.
AB  - Health inequalities often result from social inequities, and those, in turn, are
      generated by social determinants of health (SDoH). Hence, to reduce health
      inequalities, it is necessary to consider all health-related determinants.
      Disadvantages arise even before birth, and they tend to accumulate throughout an
      individual's life. Thus, policy actions intended to overcome these health
      inequalities should take place before birth and continue throughout life. This
      review aimed to describe the first steps of that Colombia has taken to reduce
      health inequalities during generational transitions through an inter-sectorial
      coordination upon SDoH. The review was guided by the question 'What are the
      implemented policy responses aimed to reduce health inequalities during
      generational transitions in Colombia, and what can be considered in order to
      improve inter-sectorial coordination?' Given the novelty of this area of
      research, the existent literature is presented more as narrative, rather than
      systematic review. Seven policies focused on five SDoH have been taken as
      examples. These policies show how Colombia plans to reduce health inequalities by
      acting upon these five SDoH: (1) early childhood development, (2) opportunities
      for education and first employment, (3) improved housing conditions, (4) social
      protection for families, and (5) vulnerable populations (e.g. elderly
      population). Additionally, more specific cases are examined in more detail that
      take place during sensitive periods in a person's life, such as pregnancy, birth,
      early childhood, entry to higher education, first time job search, family
      building, elderly years, and so on. The evidence represents Colombian's first
      steps toward reducing health inequalities during generational transitions.
      Elimination of health inequalities becomes feasible when governments recognize
      the importance of bringing opportunities to the worst-off populations, as well as
      the pivotal role of properly and well-coordinated inter-sectorial actions.

PMID- 28753106
TI  - Colorectal adenoma and cancer detection based on altered methylation pattern of
      SFRP1, SFRP2, SDC2, and PRIMA1 in plasma samples.
AB  - Aberrant methylation is one of the most frequent epigenetic alterations that can
      contribute to tumor formation. Cell-free DNA can originate from tumor tissue;
      therefore, the evaluation of methylation markers in cell-free DNA can be a
      promising method for cancer screening. Our aim was to develop a panel of
      biomarkers with altered methylation along the colorectal adenoma-carcinoma
      sequence in both colonic tissue and plasma. Methylation of selected CpG sites in
      healthy colonic (n = 15), adenoma (n = 15), and colorectal cancer (n = 15)
      tissues was analyzed by pyrosequencing. MethyLight PCR was applied to study the
      DNA methylation of SFRP1, SFRP2, SDC2, and PRIMA1 gene promoters in 121 plasma
      and 32 biopsy samples. The effect of altered promoter methylation on protein
      expression was examined by immunohistochemistry. Significantly higher (P < 0.05)
      DNA methylation levels were detected in the promoter regions of all 4 markers,
      both in CRC and adenoma tissues compared with healthy controls. Methylation of
      SFRP1, SFRP2, SDC2, and PRIMA1 promoter sequences was observed in 85.1%, 72.3%,
      89.4%, and 80.9% of plasma samples from patients with CRC and 89.2%, 83.8%, 81.1%
      and 70.3% from adenoma patients, respectively. When applied as a panel, CRC
      patients could be distinguished from controls with 91.5% sensitivity and 97.3%
      specificity [area under the curve (AUC) = 0.978], while adenoma samples could be
      differentiated with 89.2% sensitivity and 86.5% specificity (AUC = 0.937).
      Immunohistochemical analysis indicated decreasing protein levels of all 4 markers
      along the colorectal adenoma-carcinoma sequence. Our findings suggest that this
      methylation biomarker panel allows non-invasive detection of colorectal adenoma
      and cancer from plasma samples.

PMID- 28753105
TI  - The vascular basement membrane in the healthy and pathological brain.
AB  - The vascular basement membrane contributes to the integrity of the blood-brain
      barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). The
      BCECs receive support from pericytes embedded in the vascular basement membrane
      and from astrocyte endfeet. The vascular basement membrane forms a three
      dimensional protein network predominantly composed of laminin, collagen IV,
      nidogen, and heparan sulfate proteoglycans that mutually support interactions
      between BCECs, pericytes, and astrocytes. Major changes in the molecular
      composition of the vascular basement membrane are observed in acute and chronic
      neuropathological settings. In the present review, we cover the significance of
      the vascular basement membrane in the healthy and pathological brain. In stroke,
      loss of BBB integrity is accompanied by upregulation of proteolytic enzymes and
      degradation of vascular basement membrane proteins. There is yet no causal
      relationship between expression or activity of matrix proteases and the
      degradation of vascular matrix proteins in vivo. In Alzheimer's disease, changes
      in the vascular basement membrane include accumulation of Abeta, composite
      changes, and thickening. The physical properties of the vascular basement
      membrane carry the potential of obstructing drug delivery to the brain, e.g.
      thickening of the basement membrane can affect drug delivery to the brain,
      especially the delivery of nanoparticles.

PMID- 28753109
TI  - Anticipation and response: pandemic influenza in Malawi, 2009.
AB  - BACKGROUND: In 2006, Malawi developed a national influenza plan to mitigate,
      prevent and manage the burden of infection should an outbreak occur. In 2009, it
      translated its contingency plan to respond to the unfolding influenza pandemic.
      However, little is known of how Malawi translated its national influenza plan
      into response actions, or the success of these responses. OBJECTIVE: To
      investigate how Malawi translated its preparedness plan and so broaden our
      understanding of the outcomes of the responses. METHODS: We draw on data from 22
      in-depth interviews with government policymakers and people working at a policy
      level in various non-governmental organisations, conducted to assess the level of
      preparedness and the challenges of translating this. RESULTS: Through a number of
      public health initiatives, authorities developed communication strategies,
      strengthened influenza surveillance activities and updated overall goals in
      pandemic training and education. However, without influenza drills, exercises and
      simulations to test the plan, activating the pandemic plan, including
      coordinating and deploying generic infection control measures, was problematic.
      Responses during the pandemic were at times 'weak and clumsy' and failed to
      mirror the activities and processes highlighted in the preparedness plan.
      CONCLUSIONS: Participants stressed that in order to achieve a coordinated and
      successful response to mitigate and prevent the further transmission of pandemic
      influenza, good preparation was critical. The key elements which they identified
      as relevant for a rapid response included effective communications, robust
      evidence-based decision-making, strong and reliable surveillance systems and
      flexible public health responses. To effectively articulate a viable trajectory
      of pandemic responses, the potential value of simulation exercises could be given
      more consideration as a mean of sustaining good levels of preparedness and
      responses against future pandemics. These all demand a well-structured planning
      for and response to pandemic influenza strategy developed by a functioning
      scientific and policy advisory committee.

PMID- 28753110
TI  - Prehabilitation for the Enhanced Recovery After Surgery Patient.
AB  - BACKGROUND: Prehabilitation proposes that broad health interventions at the time
      of decision for surgery will improve the patient's starting functional status and
      therefore recovery. METHODS: The impact of preoperative exercise, preoperative
      nutrition, smoking cessation, alcohol cessation, anemia, and psychological
      support were reviewed. RESULTS: Interventions to improve the patient's underlying
      health typically improve recovery, although the duration and intensity necessary
      for meaningful surgical recovery benefit need further study. CONCLUSIONS:
      Preoperative health interventions may improve recovery in the postoperative
      period and patient health years later.

PMID- 28753111
TI  - A new method of subarachnoid puncture for clinical diagnosis and treatment:
      lateral atlanto-occipital space puncture.
AB  - OBJECTIVE Lumbar puncture may not be suitable for some patients needing
      subarachnoid puncture, while lateral C1-2 puncture and cisterna magna puncture
      have safety concerns. This study investigated lateral atlanto-occipital space
      puncture (also called lateral cisterna magna puncture) in patients who needed
      subarachnoid puncture for clinical diagnosis or treatment. The purpose of the
      study was to provide information on the complications and feasibility of this
      technique and its potential advantages over traditional subarachnoid puncture
      techniques. METHODS In total, 1008 lateral atlanto-occipital space puncture
      procedures performed in 667 patients were retrospectively analyzed. The success
      rate and complications were also analyzed. All patients were followed up for 1
      week after puncture. RESULTS Of 1008 lateral atlanto-occipital space punctures,
      991 succeeded and 17 failed (1.7%). Fifteen patients (2.25%) reported pain in the
      ipsilateral external auditory canal or deep soft tissue, 32 patients (4.80%) had
      a transient increase in blood pressure, and 1 patient (0.15%) had intracranial
      hypotension after the puncture. These complications resolved fully in all cases.
      There were no serious complications. CONCLUSIONS Lateral atlanto-occipital space
      puncture is a feasible technique of subarachnoid puncture for clinical diagnosis
      and treatment. It is associated with a lower rate of complications than lateral
      C1-2 puncture or traditional (suboccipital) cisterna magna puncture. It may have
      potential in the neurological diagnostic and treatment fields.

PMID- 28753112
TI  - Impact of focal cortical dysplasia Type IIIa on seizure outcome following
      anterior mesial temporal lobe resection for the treatment of epilepsy.
AB  - OBJECTIVE Temporal lobe epilepsy (TLE) is the most common type of
      pharmacoresistant focal epilepsy, for which anterior mesial temporal lobe
      resection (AMTLR) is a treatment option. Focal cortical dysplasia Type IIIa (FCD
      IIIa), a developmental lesion resulting from defects in neuronal formation and
      migration into the temporal pole (FCD I) combined with hippocampal sclerosis
      (HS), can be a neuropathological finding. In this study, the authors investigate
      the impact of FCD IIIa on seizure outcome in patients with TLE who underwent
      AMTLR. METHODS The authors performed a retrospective analysis of all patients
      with TLE who underwent AMTLR at their institution between June 2011 and April
      2014. Histopathological analysis was used to determine whether patients had HS
      together with FCD I (FCD IIIa) or HS alone. The groups were compared with regard
      to age, sex, years of epilepsy, and seizure outcome using the Engel
      classification. RESULTS A total of 51 patients with TLE underwent AMTLR at the
      authors' institution. FCD IIIa was diagnosed in 13 cases. The patients
      experienced seizures for a mean duration of 31.1 years. The mean length of follow
      up after the procedure was 18 months. All patients with FCD IIIa had a favorable
      seizure outcome (Engel Class I or II) compared with 71% of the patients with no
      pathological findings in the temporal pole (p < 0.01). CONCLUSIONS Patients with
      histopathologically proven FCD IIIa had a significantly better seizure outcome
      after AMTLR than patients with HS alone. Further effort should be made during
      presurgical evaluation to detect FCD IIIa so that the most suitable resection
      technique can be chosen and postoperative seizure outcome can be predicted for
      patient counseling.

PMID- 28753113
TI  - A potential therapy for chordoma via antibody-dependent cell-mediated
      cytotoxicity employing NK or high-affinity NK cells in combination with
      cetuximab.
AB  - OBJECTIVE Chordoma is a rare bone tumor derived from the notochord and is
      resistant to conventional therapies such as chemotherapy, radiotherapy, and
      targeting therapeutics. Expression of epidermal growth factor receptor (EGFR) in
      a large proportion of chordoma specimens indicates a potential target for
      therapeutic intervention. In this study the authors investigated the potential
      role of the anti-EGFR antibody cetuximab in immunotherapy for chordoma. METHODS
      Since cetuximab is a monoclonal antibody of the IgG1 isotype, it has the
      potential to mediate antibody-dependent cell-mediated cytotoxicity (ADCC)
      employing natural killer (NK) cells as effectors. Polymorphisms in the CD16
      allele expressed on NK cells have been shown to influence the degree of ADCC of
      tumor cells, with the high-affinity valine (V)/V allele being responsible for
      more lysis than the V/phenylalanine (F) or FF allele. Unfortunately, however,
      only approximately 10% of the population expresses the VV allele on NK cells. An
      NK cell line, NK-92, has now been engineered to endogenously express IL-2 and the
      high-affinity CD16 allele. These irradiated high-affinity (ha)NK cells were
      analyzed for lysis of chordoma cells with and without cetuximab, and the levels
      of lysis observed in ADCC were compared with those of NK cells from donors
      expressing the VV, VF, and FF alleles. RESULTS Here the authors demonstrate for
      the first time 1) that cetuximab in combination with NK cells can mediate ADCC of
      chordoma cells; 2) the influence of the NK CD16 polymorphism in cetuximab
      mediated ADCC for chordoma cell lysis; 3) that engineered haNK cells-that is,
      cells transduced to express the CD16 V158 FcgammaRIIIa receptor-bind cetuximab
      with similar affinity to normal NK cells expressing the high-affinity VV allele;
      and 4) that irradiated haNK cells induce ADCC with cetuximab in chordoma cells.
      CONCLUSIONS These studies provide rationale for the use of cetuximab in
      combination with irradiated haNK cells for therapy for chordoma.

PMID- 28753114
TI  - Erratum. Effectiveness of endoscopic surgery for supratentorial hypertensive
      intracerebral hemorrhage: a comparison with craniotomy.

PMID- 28753116
TI  - Letter to the Editor. Misinterpretations in the citation.

PMID- 28753115
TI  - Brachyury gene copy number gain and activation of the PI3K/Akt pathway:
      association with upregulation of oncogenic Brachyury expression in skull base
      chordoma.
AB  - OBJECTIVE Chordoma is a slow-growing but clinically malignant tumor, and the
      prognosis remains poor in many cases. There is a strong impetus to develop more
      effective targeted molecular therapies. On this basis, the authors investigated
      the potential of Brachyury, a transcription factor involved in notochord
      development, as a candidate molecular target for the treatment of chordoma.
      METHODS Brachyury gene copy number and expression levels were evaluated by
      quantitative polymerase chain reaction in 27 chordoma samples, and the
      transcriptomes of Brachyury high-expression tumors (n = 4) and Brachyury low
      expression tumors (n = 4) were analyzed. A chordoma cell line (U-CH2) was used to
      investigate the signaling pathways that regulate Brachyury expression. RESULTS
      All chordoma specimens expressed Brachyury, and expression levels varied widely.
      Patients with higher Brachyury expression had significantly shorter progression
      free survival (5 months, n = 11) than those with lower expression (13 months, n =
      16) (p = 0.03). Somatic copy number gain was confirmed in 12 of 27 (44%) cases,
      and copy number was positively correlated with Brachyury expression (R = 0.61, p
      < 0.001). Expression of PI3K/Akt pathway genes was upregulated in Brachyury high
      expression tumors, and suppression of PI3K signaling led to reduced Brachyury
      expression and inhibition of cell growth in the U-CH2 chordoma cell line.
      CONCLUSIONS Activation of the PI3K/Akt pathway and Brachyury copy number gain are
      strongly associated with Brachyury overexpression, which appears to be a key
      event in chordoma growth regulation. These findings suggest that targeting
      Brachyury and PI3K/Akt signaling may be an effective new approach for treating
      chordoma.

PMID- 28753117
TI  - New-onset seizure during and after brain tumor excision: a risk assessment
      analysis.
AB  - OBJECTIVE Prophylactic use of antiepileptic drugs (AEDs) in seizure-naive brain
      tumor patients remains a topic of debate. This study aimed to characterize a
      subset of patients at highest risk for new-onset perioperative seizures (i.e.,
      intraoperative and postoperative seizures occurring within 30 days of surgery)
      who may benefit from prophylactic AEDs. METHODS The authors conducted a
      retrospective case-control study of all adults who had undergone tumor resection
      or biopsy at the authors' institution between January 1, 2004, and June 31, 2015.
      All patients with a history of preoperative seizures, posterior fossa tumors,
      pituitary tumors, and parasellar tumors were excluded. A control group was
      matched to the seizure patients according to age (+/- 0 years). Demographic data,
      clinical status, operative data, and postoperative course data were collected and
      analyzed. RESULTS Among 1693 patients who underwent tumor resection or biopsy,
      549 (32.4%) had never had a preoperative seizure. Of these 549 patients, 25
      (4.6%) suffered a perioperative seizure (Group 1). A total of 524 patients
      (95.4%) who remained seizure free were matched to Group 1 according to age (+/- 0
      years), resulting in 132 control patients (Group 2), at an approximate ratio of
      1:5. There were no differences between the patient groups in terms of age, sex,
      race, relationship status, and neurological deficits on presentation.
      Histological subtype (infiltrating glioma vs meningioma vs other, p = 0.041),
      intradural tumor location (p < 0.001), intraoperative cortical stimulation (p =
      0.004), and extent of resection (less than gross total, p = 0.002) were
      associated with the occurrence of perioperative seizures. CONCLUSIONS While most
      seizure-naive brain tumor patients do not benefit from perioperative seizure
      prophylaxis, such treatment should be considered in high-risk patients with
      supratentorial intradural tumors, in patients undergoing intraoperative cortical
      stimulation, and in patients in whom subtotal resection is likely.

PMID- 28753118
TI  - Delayed compression of the common peroneal nerve following rotational lateral
      gastrocnemius flap: case report.
AB  - The authors present a case of delayed peroneal neuropathy following a lateral
      gastrocnemius rotational flap reconstruction. The patient presented 1.5 years
      after surgery with a new partial foot drop, which progressed over 3 years. At
      operation, a fascial band on the deep side of the gastrocnemius flap was
      compressing the common peroneal nerve proximal to the fibular head, correlating
      with preoperative imaging. Release of this fascial band and selective muscle
      resection led to immediate improvement in symptoms postoperatively.

PMID- 28753119
TI  - Advocacy Journey Promoting Child Sexual Abuse Prevention in Hong Kong.
AB  - In a country without a mandatory child abuse reporting system, advocacy for child
      welfare law can be a tedious and difficult process. This article documents a 10
      year advocacy journey based on the capacity-building concept in social
      sustainability theory which aims to: raise public awareness of child sexual
      abuse, provide an idea for branding an inquiry column, and connect advocacy
      efforts to law reforms. Over the past decade in Hong Kong, a total of 336 public
      inquiries were anonymously sent to Wu Miu Column and published in three local
      major newspapers. Among these inquiries, 131 inquiries involved child sexual
      abuse that the "affected individuals" were molested in school or at home and knew
      the abusers but did not report their cases to child protection services.
      Inquirers reported more male than female abusers. Proportionally and
      significantly, female abusers tended to abuse younger children, compared to male
      abusers who tended to abuse older children. Many abusers were minors who abused
      younger children, which explains people's reluctance to report the abuse to child
      protection services. The discovery of this underage phenomenon motivated child
      advocates to challenge the common law presumption that a boy under the age of 14
      is incapable of sexual intercourse. Social workers in this advocacy journey must
      sustain continuous efforts to prevent youth from becoming future perpetrators.

PMID- 28753120
TI  - Dynamic analysis of forces in the lumbar spine during bag carrying.
AB  - OBJECTIVE: The intervertebral disc supports axial and shear forces generated
      during tasks such as lifting and carrying weights. The objective of this study
      was to determine the forces in the lumbar spine of workers carrying a bag on the
      head, on the shoulder and on the anterior part of the trunk. METHODS: Kinematic
      measurements were recorded for 10 subjects carrying bags of 10, 20 and 25 kg on
      each of the three aforementioned positions. A simple dynamic model implemented in
      a custom program was then developed to determine the lumbar forces using the
      accelerations and positions obtained from the kinematic analysis. RESULTS: The
      analyses yielded a maximum compressive force of 2338.4 +/- 422 N when a 25-kg bag
      was carried on the anterior part of the trunk. CONCLUSION: Carrying bags on the
      anterior part of the trunk generated higher lumbar forces compared to those
      developed by carrying the bag on the head or on the shoulder. Force levels
      suggest that this activity represents a moderate risk for the subjects. However,
      future biomechanical models should be developed to analyze the cumulative effect
      in the discs when longer periods of time are spent in this activity.

PMID- 28753121
TI  - Successful treatment of refractory neutropenia in Felty's syndrome with
      rituximab.

PMID- 28753122
TI  - Stepwise Psychosocial Palliative Care: A New Approach to the Treatment of
      Posttraumatic Stress Disorder at the End of Life.
AB  - Although evidence-based therapies for Posttraumatic Stress Disorder (PTSD) exist
      for physically healthy populations, these often do not adequately address PTSD in
      dying patients. Particularly because these interventions require 8-16 weekly
      sessions, and the median stay in U.S. hospices is 17.5 days (National Hospice and
      Palliative Care Organization [NHPCO], 2015 ), there is a potentially serious
      timing mismatch. Moreover, these treatments may temporarily increase trauma
      symptoms (Nishith, Resick, & Griffin, 2002 ), resulting in some patients dying in
      greater distress than had they not received care. The Stepwise Psychosocial
      Palliative Care (SPPC) model presented in this article compensates for these
      difficulties by embracing a palliative care approach to PTSD. Although it
      utilizes techniques drawn from existing PTSD interventions, these are re-ordered
      and utilized in a time-responsive, patient-centered manner that takes into
      account prognosis, fatigue, and logistical concerns. The SPPC approach is further
      considered with respect to existing social work palliative care competencies
      (Gwyther et al., 2005 ) and a case study is used to demonstrate its application.

PMID- 28753123
TI  - Titanium dioxide nanoparticles preferentially bind in subdomains IB, IIA of HSA
      and minor groove of DNA.
AB  - Titanium dioxide nanoparticles (TiO2-NPs) interaction with human serum albumin
      (HSA) and DNA was studied by UV-visible spectroscopy, spectrofluorescence,
      circular dichroism (CD), and transmission electron microscopy (TEM) to analyze
      the binding parameters and protein corona formation. TEM revealed protein corona
      formation on TiO2-NPs surface due to adsorption of HSA. Intrinsic fluorescence
      quenching data suggested significant binding of TiO2-NPs (avg. size 14.0 nm) with
      HSA. The Stern-Volmer constant (Ksv) was determined to be 7.6 * 102 M-1 (r2 =
      0.98), whereas the binding constant (Ka) and number of binding sites (n) were
      assessed to be 5.82 * 102 M-1 and 0.97, respectively. Synchronous fluorescence
      revealed an apparent decrease in fluorescence intensity with a red shift of 2 nm
      at Deltalambda = 15 nm and Deltalambda = 60 nm. UV-visible analysis also provided
      the binding constant values for TiO2-NPs-HSA and TiO2-NPs-DNA complexes as 2.8 *
      102 M-1 and 5.4 * 103 M-1. The CD data demonstrated loss in alpha-helicity of HSA
      and transformation into beta-sheet, suggesting structural alterations by TiO2
      NPs. The docking analysis of TiO2-NPs with HSA revealed its preferential binding
      with aromatic and non-aromatic amino acids in subdomain IIA and IB hydrophobic
      cavity of HSA. Also, the TiO2-NPs docking revealed the selective binding with A-T
      bases in minor groove of DNA.

PMID- 28753124
TI  - Two-step membrane binding by the bacterial SRP receptor enable efficient and
      accurate Co-translational protein targeting.
AB  - The signal recognition particle (SRP) delivers ~30% of the proteome to the
      eukaryotic endoplasmic reticulum, or the bacterial plasma membrane. The precise
      mechanism by which the bacterial SRP receptor, FtsY, interacts with and is
      regulated at the target membrane remain unclear. Here, quantitative analysis of
      FtsY-lipid interactions at single-molecule resolution revealed a two-step
      mechanism in which FtsY initially contacts membrane via a Dynamic mode, followed
      by an SRP-induced conformational transition to a Stable mode that activates FtsY
      for downstream steps. Importantly, mutational analyses revealed extensive auto
      inhibitory mechanisms that prevent free FtsY from engaging membrane in the Stable
      mode; an engineered FtsY pre-organized into the Stable mode led to indiscriminate
      targeting in vitro and disrupted FtsY function in vivo. Our results show that the
      two-step lipid-binding mechanism uncouples the membrane association of FtsY from
      its conformational activation, thus optimizing the balance between the efficiency
      and fidelity of co-translational protein targeting.

PMID- 28753125
TI  - Reaction times can reflect habits rather than computations.
AB  - Reaction times (RTs) are assumed to reflect the underlying computations required
      for making decisions and preparing actions. Recent work, however, has shown that
      movements can be initiated earlier than typically expressed without affecting
      performance; hence, the RT may be modulated by factors other than computation
      time. Consistent with that view, we demonstrated that RTs are influenced by prior
      experience: when a previously performed task required a specific RT to support
      task success, this biased the RTs in future tasks. This effect is similar to the
      use-dependent biases observed for other movement parameters such as speed or
      direction. Moreover, kinematic analyses revealed that these RT biases could occur
      without changing the underlying computations used to perform the action. Thus the
      RT is not solely determined by computational requirements but is an independent
      parameter that can be habitually set by prior experience.

PMID- 28753126
TI  - Structure and topology around the cleavage site regulate post-translational
      cleavage of the HIV-1 gp160 signal peptide.
AB  - Like all other secretory proteins, the HIV-1 envelope glycoprotein gp160 is
      targeted to the endoplasmic reticulum (ER) by its signal peptide during
      synthesis. Proper gp160 folding in the ER requires core glycosylation, disulfide
      bond formation and proline isomerization. Signal-peptide cleavage occurs only
      late after gp160 chain termination and is dependent on folding of the soluble
      subunit gp120 to a near-native conformation. We here detail the mechanism by
      which co-translational signal-peptide cleavage is prevented. Conserved residues
      from the signal peptide and residues downstream of the canonical cleavage site
      form an extended alpha-helix in the ER membrane, which covers the cleavage site,
      thus preventing cleavage. A point mutation in the signal peptide breaks the alpha
      helix allowing co-translational cleavage. We demonstrate that postponed cleavage
      of gp160 enhances functional folding of the molecule. The change to early
      cleavage results in decreased viral fitness compared to wild-type HIV.

PMID- 28753127
TI  - IGF2 mRNA binding protein-2 is a tumor promoter that drives cancer proliferation
      through its client mRNAs IGF2 and HMGA1.
AB  - The gene encoding the Insulin-like Growth Factor 2 mRNA binding protein 2/IMP2 is
      amplified and overexpressed in many human cancers, accompanied by a poorer
      prognosis. Mice lacking IMP2 exhibit a longer lifespan and a reduced tumor burden
      at old age. Herein we show in a diverse array of human cancer cells that IMP2
      overexpression stimulates and IMP2 elimination diminishes proliferation by 50
      80%. In addition to its known ability to promote the abundance of Insulin-like
      Growth Factor 2/IGF2, we find that IMP2 strongly promotes IGF action, by binding
      and stabilizing the mRNA encoding the DNA binding protein HMGA1, a known
      oncogene. HMGA1 suppresses the abundance of IGF binding protein 2/IGFBP2 and
      Grb14, inhibitors of IGF action. IMP2 stabilization of HMGA1 mRNA plus IMP2
      stimulated IGF2 production synergistically drive cancer cell proliferation and
      account for IMP2's tumor promoting action. IMP2's ability to promote
      proliferation and IGF action requires IMP2 phosphorylation by mTOR.

PMID- 28753128
TI  - Imatinib-Induced Interstitial Pneumonitis Successfully Switched to Nilotinib in a
      Patient with Prior History of Mycobacterium tuberculosis Infection.

PMID- 28753129
TI  - Glomerular and Tubular Functions in Children and Adults with Transfusion
      Dependent Thalassemia.
AB  - This study aimed at assessing renal functions in patients with transfusion
      dependent thalassemia (TDT). Fifty patients and 30 controls were enrolled in this
      prospective study. Serum levels of electrolytes and albumin were measured by a
      spectrophotometer. Serum levels of cystatin-C and urinary levels of beta2
      microglobulin were measured by nephelometric method. Thirty-eight patients were
      receiving deferasirox and 8 were on deferiprone. Serum electrolytes and albumin
      levels of the patients were found to be within normal ranges. Urinary beta2
      microglobulin and serum cystatin-C levels were significantly higher in patients
      than controls. They did not significantly differ between the subgroup of patients
      on deferiprone and the control group, whereas they were found to be higher in
      patients using deferasirox compared to controls. Urinary beta2-microglobulin
      levels significantly increased in patients who were receiving high-dose
      deferasirox compared to those who were receiving a daily dose of 15-20 mg/kg or
      controls. Subclinical renal injury may be present in TDT patients.

PMID- 28753130
TI  - Pilot study of quality of care training and knowledge in Sub-Saharan African
      medical schools.
AB  - Objectives: To identify the level of knowledge and competencies related to
      quality of care during medical education in sub-Saharan African medical schools.
      Methods: A cross-sectional study design was utilized to examine the capacity of
      medical schools in sub-Saharan African (SSA) countries to teach about the
      concepts of quality of care and the inclusion of these concepts in their
      curriculum. A purposeful convenience sampling technique was used to select
      participants from 25 medical schools in 5 sub-Saharan African countries.
      Respondents included medical school deans or senior academic personnel.  A survey
      was developed using the Institute of Medicine's definition of quality of care as
      the guiding framework.  Sample means and summary statistics were used to present
      the results of the survey responses. Results: While 45% of the schools surveyed
      are teaching on at least one of the six domains of the Institute of Medicine's
      definition of quality of care, there are some schools who report not teaching
      about quality at all, or that they "do not know". Despite these low numbers, when
      asked about topics related to quality of care, many schools are teaching applied
      management related topics and almost all schools teach about equity and patient
      centered care. Conclusions: The results have important impacts both for
      incorporating quality of care into medical education and for practitioners.  The
      tool developed for this study can be used in future qualitative and quantitative
      studies to further understanding of how to improve the teaching and learning
      about quality of care in medical schools. Keywords: quality of care, medical
      schools, sub-Saharan Africa, medical errors, healthcare improvement.

PMID- 28753131
TI  - Nuclear fission: a review of experimental advances and phenomenology.
AB  - In the last two decades, through technological, experimental and theoretical
      advances, the situation in experimental fission studies has changed dramatically.
      With the use of advanced production and detection techniques both much more
      detailed and precise information can now be obtained for the traditional regions
      of fission research and, crucially, new regions of nuclei have become routinely
      accessible for fission studies. This work first of all reviews the recent
      developments in experimental fission techniques, in particular the resurgence of
      transfer-induced fission reactions with light and heavy ions, the emerging use of
      inverse-kinematic approaches, both at Coulomb and relativistic energies, and of
      fission studies with radioactive beams. The emphasis on the fission-fragment mass
      and charge distributions will be made in this work, though some of the other
      fission observables, such as prompt neutron and gamma-ray emission will also be
      reviewed. A particular attention will be given to the low-energy fission in the
      so far scarcely explored nuclei in the very neutron-deficient lead region. They
      recently became the focus for several complementary experimental studies, such as
      beta-delayed fission with radioactive beams at ISOLDE(CERN), Coulex-induced
      fission of relativistic secondary beams at FRS(GSI), and several prompt fusion
      fission studies. The synergy of these approaches allows a unique insight in the
      new region of asymmetric fission around [Formula: see text]Hg, recently
      discovered at ISOLDE. Recent extensive theoretical efforts in this region will
      also be outlined. The unprecedented high-quality data for fission fragments,
      completely identified in Z and A, by means of reactions in inverse kinematics at
      FRS(GSI) and VAMOS(GANIL) will be also reviewed. These experiments explored an
      extended range of mercury-to-californium elements, spanning from the neutron
      deficient to neutron-rich nuclides, and covering both asymmetric, symmetric and
      transitional fission regions. Some aspects of heavy-ion induced fusion-fission
      and quasifission reactions will be also discussed, which reveal their dynamical
      features, such as the fission time scale. The crucial role of the multi-chance
      fission, probed by means of multinucleon-transfer induced fission reactions, will
      be highlighted. The review will conclude with the discussion of the new
      experimental fission facilities which are presently being brought into operation,
      along with promising 'next-generation' fission approaches, which might become
      available within the next decade.

PMID- 28753132
TI  - A deep learning framework for supporting the classification of breast lesions in
      ultrasound images.
AB  - In this research, we exploited the deep learning framework to differentiate the
      distinctive types of lesions and nodules in breast acquired with ultrasound
      imaging. A biopsy-proven benchmarking dataset was built from 5151 patients cases
      containing a total of 7408 ultrasound breast images, representative of semi
      automatically segmented lesions associated with masses. The dataset comprised
      4254 benign and 3154 malignant lesions. The developed method includes histogram
      equalization, image cropping and margin augmentation. The GoogLeNet
      convolutionary neural network was trained to the database to differentiate benign
      and malignant tumors. The networks were trained on the data with augmentation and
      the data without augmentation. Both of them showed an area under the curve of
      over 0.9. The networks showed an accuracy of about 0.9 (90%), a sensitivity of
      0.86 and a specificity of 0.96. Although target regions of interest (ROIs) were
      selected by radiologists, meaning that radiologists still have to point out the
      location of the ROI, the classification of malignant lesions showed promising
      results. If this method is used by radiologists in clinical situations it can
      classify malignant lesions in a short time and support the diagnosis of
      radiologists in discriminating malignant lesions. Therefore, the proposed method
      can work in tandem with human radiologists to improve performance, which is a
      fundamental purpose of computer-aided diagnosis.

PMID- 28753133
TI  - Performance evaluation of a high-resolution brain PET scanner using four-layer
      MPPC DOI detectors.
AB  - A high-resolution positron emission tomography (PET) scanner, dedicated to brain
      studies, was developed and its performance was evaluated. A four-layer depth of
      interaction detector was designed containing five detector units axially lined up
      per layer board. Each of the detector units consists of a finely segmented (1.2
      mm) LYSO scintillator array and an 8  *  8 array of multi-pixel photon counters.
      Each detector layer has independent front-end and signal processing circuits, and
      the four detector layers are assembled as a detector module. The new scanner was
      designed to form a detector ring of 430 mm diameter with 32 detector modules and
      168 detector rings with a 1.2 mm pitch. The total crystal number is 655 360. The
      transaxial and axial field of views (FOVs) are 330 mm in diameter and 201.6 mm,
      respectively, which are sufficient to measure a whole human brain. The single
      event data generated at each detector module were transferred to the data
      acquisition servers through optical fiber cables. The single-event data from all
      detector modules were merged and processed to create coincidence event data in on
      the-fly software in the data acquisition servers. For image reconstruction, the
      high-resolution mode (HR-mode) used a 1.2 mm2 crystal segment size and the high
      speed mode (HS-mode) used a 4.8 mm2 size by collecting 16 crystal segments of 1.2
      mm each to reduce the computational cost. The performance of the brain PET
      scanner was evaluated. For the intrinsic spatial resolution of the detector
      module, coincidence response functions of the detector module pair, which faced
      each other at various angles, were measured by scanning a 0.25 mm diameter 22Na
      point source. The intrinsic resolutions were obtained with 1.08 mm full width at
      half-maximum (FWHM) and 1.25 mm FWHM on average at 0 and 22.5 degrees in the
      first layer pair, respectively. The system spatial resolutions were less than 1.0
      mm FWHM throughout the whole FOV, using a list-mode dynamic RAMLA (LM-DRAMA). The
      system sensitivity was 21.4 cps kBq-1 as measured using an 18F line source
      aligned with the center of the transaxial FOV. High count rate capability was
      evaluated using a cylindrical phantom (20 cm diameter  *  70 cm length),
      resulting in 249 kcps in true and 27.9 kcps at 11.9 kBq ml-1 at the peak count in
      a noise equivalent count rate (NECR_2R). Single-event data acquisition and on-the
      fly software coincidence detection performed well, exceeding 25 Mcps and 2.3 Mcps
      for single and coincidence count rates, respectively. Using phantom studies, we
      also demonstrated its imaging capabilities by means of a 3D Hoffman brain phantom
      and an ultra-micro hot-spot phantom. The images obtained were of acceptable
      quality for high-resolution determination. As clinical and pre-clinical studies,
      we imaged brains of a human and of small animals.

PMID- 28753134
TI  - sMLACF: a generalized expectation-maximization algorithm for TOF-PET to
      reconstruct the activity and attenuation simultaneously.
AB  - The 'simultaneous maximum-likelihood attenuation correction factors' (sMLACF)
      algorithm presented here, is an iterative algorithm to calculate the maximum
      likelihood estimate of the activity lambda and the attenuation factors a in time
      of-flight positron emission tomography, and this from emission data only. Hence
      sMLACF is an alternative to the MLACF algorithm. sMLACF is derived using the
      generalized expectation-maximization principle by introducing an appropriate set
      of complete data. The resulting iteration step yields a simultaneous update of
      lambda and a which, in addition, enforces in a natural way the constraints
      [Formula: see text] where [Formula: see text] is a fixed lower bound that ensures
      the boundedness of the reconstructed activities. Some properties-like the
      monotonic increase of the likelihood and the asymptotic regularity of the
      estimated [Formula: see text]-of sMLACF are proven. Comparison of sMLACF with
      MLACF for two data sets reveals that both algorithms show very similar results,
      although sMLACF converges slower.

PMID- 28753135
TI  - Personalizing Environmental Health: At the Intersection of Precision Medicine and
      Occupational Health in the Military.
AB  - : Recent efforts in precision medicine present unique opportunities for military
      environmental and occupational health. Risk assessments can be refined by
      individualized risk factors such as genomics, and health status can be monitored
      and informed using mobile health (mHealth) devices. The military currently
      monitors exposures with service-wide databases and has one of the world's largest
      biobanks of serum samples available for health surveillance. New approaches are
      being developed for risk assessment, novel exposure-based biomarkers, and mobile
      applications to combine the facile collection of exposure data with tracking and
      planning utility. Planning by military leaders and coordination with national
      efforts puts the Department of Defense (DoD) in a unique position to benefit both
      Service Members and the nation, as reviewed in a symposium cosponsored by the DoD
      and the Johns Hopkins University-Applied Physics Laboratory (October 27 to 28,
      2015).

PMID- 28753136
TI  - Implementation of a Personalized, Cost-Effective Physical Therapy Approach
      (Coach2Move) for Older Adults: Barriers and Facilitators.
AB  - BACKGROUND AND PURPOSE: This article reports on a recent randomized clinical
      trial that showed a personalized approach to physical therapy (Coach2Move) by a
      physical therapist specialized in geriatrics (PTG) to be more cost-effective than
      usual physical therapy care in people with mobility problems (n = 130, mean age =
      78 years). METHODS: We used an explanatory mixed-methods sequential design
      alongside the randomized clinical trial to gain insight into (a) the contrast
      between the 2 interventions, (b) the fidelity of the Coach2Move delivery; (c)
      PTGs' experiences of Coach2Move; and (d) possible barriers and facilitators for
      future implementation. The study included 13 PTGs educated in the strategy and 13
      physical therapists with expertise in geriatrics delivering the usual care. In
      total, 106 medical records were available for assessment: 57 (85%) Coach2Move, 49
      (75%) usual care. Quantitative process indicators were used to analyze electronic
      medical records to determine contrasts in the phases of clinical reasoning. The
      fidelity of the delivery was tested using indicator scores focusing on 4 key
      elements of Coach2Move. In-depth interviews with Coach2Move therapists were
      thematically analyzed to explore experiences and facilitators/barriers related to
      implementation. RESULTS AND DISCUSSION: Indicator scores showed significant and
      clinically relevant contrasts in all phases of clinical reasoning, with
      consistently higher scores among PTGs, except for the treatment plan. Moreover,
      the fidelity of Coach2Move delivery was more than 70% in all phases, except the
      evaluation phase (53%). Experiences of Coach2Move were positive. In particular,
      extended intake allowing motivational interviewing, physical examination and an
      in-depth problem analysis, and shared goal setting were considered valuable.
      Facilitators for implementation were the addition of a Coach2Move medical record,
      frequent coaching by the researcher, and readiness to change in the therapist.
      Barriers were (1) having to use 2 parallel electronic medical record systems, (2)
      having to clear the calendar to schedule an intake of 90 minutes, (3) fear of
      losing income, (4) the sense that patients do not want to change their lifestyle,
      and (5) not acknowledging that increasing physical activity is an important goal
      for older adults with mobility problems. CONCLUSIONS: Physical therapy based on
      the Coach2Move strategy is substantially different from usual care. Future
      implementation should focus on increasing regular evaluation and feedback, taking
      into account individuals' contextual factors, and improving organizational
      facilities while mitigating income loss.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- 28753137
TI  - Life-Threatening and Fatal Adverse Drug Events in a Danish University Hospital.
AB  - OBJECTIVES: Detection of adverse drug events (ADEs) in Danish hospitals relies on
      health care professionals' incident reporting to a national database for adverse
      events, but the method is incomplete; thus, fatal and life-threatening ADEs may
      remain unrecognized.The objectives of this study were to examine the occurrence
      of life-threatening and fatal ADEs in population of hospitalized patients with
      suspected adverse outcome and to compare these findings with the actual number of
      reported ADEs in the study period of 3 months. METHODS: Study was designed as a
      cross-sectional study of adult population, hospitalized for more than 24 hours,
      having an unplanned transfer to an intensive care unit (ICU), or having
      unexpected death. Medical records were retrospectively screened by the Global
      Trigger Tool. All positive triggers were assessed for ADEs by a clinical
      pharmacologist. RESULTS: Of the 26,176 patients admitted in the study period, 105
      had an unplanned transfer to the ICU and 36 died unexpectedly. In total, 15
      positive triggers were identified in 10 patients. Life-threatening ADEs accounted
      for 7.6% (8/105) of patients transferred to the ICU, and fatal ADEs constituted
      5.5% (2/36) of the deceased patients. Life-threatening and fatal ADEs
      corresponded to an overall prevalence of 0.04% (10/26,176). Most ADEs were
      related to hemorrhages and respiratory problems. No serious or fatal ADEs were
      reported in the incident reporting system in the study period. CONCLUSIONS: Ten
      life-threatening and fatal ADEs were uncovered as not reported in the incident
      reporting system. Further steps are needed for recognition and prevention of this
      patient safety challenge.

PMID- 28753138
TI  - The Critical Research Evaluation Tool (CRET): A Teaching and Learning Tool to
      Evaluate Research for Cultural Competence.
AB  - The aim of this study was to present the Critical Research Evaluation Tool (CRET)
      which teaches evaluation of the researchers' worldview, applicability to
      multicultural populations, and ethics surrounding potential harms to communities.
      To provide best cultural care nurses' need to understand how
      historical/social/political experiences impact health and also influence
      research. The Student using the CRET reported receiving a strong foundation in
      research fundamentals, gaining a better understanding of critical frameworks in
      research, and learning more about themselves and reflecting on their own
      privileges and biases. The CRET provides nursing students and nursing faculty
      with a tool for examining diversity and ultimately decreasing health disparity.

PMID- 28753139
TI  - Electronic Cigarette Use Among Counseled Tobacco Users Hospitalized in 2015.
AB  - OBJECTIVES: Few studies have examined the prevalence of electronic cigarette use
      among the inpatient population regardless of the patients' cessation goals. The
      objectives of this study were to examine the prevalence of electronic cigarette
      use among counseled tobacco users admitted to 2 academic hospitals. METHODS:
      Cross-sectional data of hospitalized adult tobacco users who were admitted
      between January 1, 2015 and December 31, 2015 and who received bedside tobacco
      cessation counseling from a tobacco treatment service counselor were examined.
      Demographic and smoking history items were compared as a function of electronic
      cigarette use using chi-square and independent t tests. Logistic regression was
      used to test independent associations with electronic cigarette use. RESULTS: Of
      2194 hospitalized tobacco users counseled, 22% had used an electronic cigarette.
      Most of these patients used electronic cigarettes to quit or reduce use of
      combustible cigarettes. Adjusted odds of electronic cigarette use were higher for
      females (adjusted odds ratio [AOR] 0.60 for male patients, 95% confidence
      interval [CI] 0.47-0.76), younger patients (AOR 0.98 for older patients, 95% CI
      0.97-0.99), and individuals who initiated tobacco use earlier in life (AOR 0.97
      for later smoking initiation, 95% CI 0.95-0.99). CONCLUSIONS: Screening
      hospitalized cigarette smokers for electronic cigarette use offers an opportunity
      to counsel all patients on evidence-based quit aids. Young, female patients are
      most likely to use electronic cigarettes and may benefit most from directed
      discussions about electronic cigarette use and Federal Drug Administration
      approved cessation methods during smoking cessation counseling.

PMID- 28753140
TI  - RE: Skin Necrosis After Implantation with the Baha Attract: A Case Report and
      Review of the Literature: Chen SY, Mancuso D, and Lalwani AK. OTOL NEUROTOL 2017
      MAR;38(3): 364-367.

PMID- 28753141
TI  - Atrial Esophageal Fistula Secondary to Ablation for Atrial Fibrillation: A Case
      Series and Review of the Literature.
AB  - This article describes 2 patients who presented to our institution with left
      atrial esophageal fistula after atrial fibrillation ablation; it also compares
      our experience with other atrial esophageal fistula cases reported in the
      literature. We performed a retrospective review of 2 patients who presented to
      our hospital between July 2015 and September 2015 with atrial esophageal fistula.
      Patient A, a 57-year-old man, presented 31 days postablation with a fever and
      right-sided weakness. A chest computed tomography showed gas in the left atrium
      and esophagus; an echocardiogram confirmed the diagnosis of atrial esophageal
      fistula. The patient subsequently underwent a left thoracotomy. Postoperative
      recovery was poor and included significant coagulopathy, sepsis, cardiogenic
      shock, and multisystem organ failure. The patient died on postoperative day 28.
      Patient B, a 77-year-old man, presented 21 days post-atrial fibrillation ablation
      with left-arm weakness and altered mental status. An esophagram was performed and
      showed no evidence of an esophageal perforation. Because of positive cultures and
      worsening altered mental status, the patient underwent a head computed
      tomography, which showed pneumocephalus, leading to our suspicion of the atrial
      esophageal fistula. A follow-up chest computed tomography confirmed the atrial
      esophageal fistula. Treatment included an esophagectomy and repair of the atrium.
      Unfortunately, the atrial esophageal fistula closure dehisced, and the patient
      developed acute respiratory failure and cardiac tamponade, which led to
      cardiopulmonary arrest, and the patient died on postoperative day 10. Based on
      our experience, and the literature, we recommend that a chest computed tomography
      be immediately performed on patients presenting with the described symptoms after
      a recent atrial fibrillation ablation.

PMID- 28753143
TI  - Social Media and Consent: Are Patients Adequately Informed?

PMID- 28753144
TI  - "Cartoon Analgesia in the Pediatric Plastic Surgery Population."

PMID- 28753145
TI  - Reply to Varghese BT: (Optimising outcomes in Pharyngoesophageal Reconstruction
      and Neck Resurfacing: 10-Year Experience of 294 Cases).

PMID- 28753146
TI  - Facial Gender Confirmation Surgery: A New Nomenclature.

PMID- 28753147
TI  - Operating Principles for Plastic Surgeons.

PMID- 28753148
TI  - The Role of a 'Holistic' Journal Club.

PMID- 28753149
TI  - Breast Implant Illness: Symptoms, Patient Concerns, and the Power of Social
      Media.

PMID- 28753150
TI  - "Establishment of an Acquired Lymphedema Model in the Mouse Hindlimb: Technical
      Refinement and Molecular Characteristics."

PMID- 28753152
TI  - Comment on "A Novel Method of Human Adipose-Derived Stem Cell Isolation with
      Resultant Increased Cell Yield".

PMID- 28753154
TI  - Adipose-Derived Stem Cells and Vascularized Lymph Node Transfers Successfully
      Treat Mouse Hindlimb Secondary Lymphedema by Early Reconnection of the Lymphatic
      System and Lymphangiogenesis.

PMID- 28753156
TI  - "Adipose-Derived Stem Cells and Vascularized Lymph Node Transfers Successfully
      Treat Mouse Hindlimb Secondary Lymphedema by Early Reconnection of the Lymphatic
      System and Lymphangiogenesis."

PMID- 28753158
TI  - Evidence-Based Medicine: Face Lift.

PMID- 28753160
TI  - "Fat Grafting in the Hollow Upper Eyelids and Volumetric Upper Blepharoplasty".
AB  - BACKGROUND: Periorbital volume loss creates a shadow frame, where traditional
      excisional blepharoplasties may aggravate the situation. Divergence in filling
      treatments establishes a demand for simple and reproducible techniques to achieve
      consistent results. Here, the author's hollow upper eyelid evaluation and
      treatment approach are presented. METHODS: A retrospective photographic analysis
      was conducted for 32 women who underwent fat grafting on the hollow upper eyelids
      between 2012 and 2016. Pre- and postoperative evaluations of upper eyelid ratios
      at the medial and lateral corneal limbus, together with lateral contour
      modifications, were used to determine the efficacy of the technique to restore
      the youthful proportions and contours. RESULTS: Preoperative analysis showed 20
      eyelids with an inner shadow or A-pattern and 44 eyelids with the complete
      extension of the hollow or C-pattern. Three patients presented mild
      blepharoptosis, and eight patients had undergone a previous upper blepharoplasty.
      Mean grafting volume was 0.4 cc in the deep plane and 2.8 cc in the superficial
      plane. Fat grafting exclusively was performed in six patients, improving all
      ratios and correcting the A-pattern deformity. Volumetric upper blepharoplasty
      combining fat grafting in two levels and orbicularis oculi muscle imbrication was
      performed in 26 patients, correcting every inverted ratio (p < 0.001).On the
      lateral view, all cases with a concave pattern changed to a convex one,
      regardless of the approach employed. CONCLUSIONS: Synergy between fat grafting
      and orbicularis imbrication proved adequate to restore the lateral convex contour
      and return youthful proportions to the hollow upper eyelids.

PMID- 28753161
TI  - Impact of Exercise on Cardiometabolic Component Risks in Spinal Cord-injured
      Humans.
AB  - PURPOSE: Spinal cord injury (SCI) creates a complex pathology, characterized by
      low levels of habitual physical activity and an increased risk of cardiometabolic
      disease. This study aimed to assess the effect of a moderate-intensity upper-body
      exercise training intervention on biomarkers of cardiometabolic component risks,
      adipose tissue metabolism, and cardiorespiratory fitness in persons with SCI.
      METHODS: Twenty-one inactive men and women with chronic (>1 yr) SCI (all
      paraplegic injuries) 47 +/- 8 yr of age (mean +/- SD) were randomly allocated to
      either a 6-wk prescribed home-based exercise intervention (INT; n = 13) or
      control group (CON; n = 8). Participants assigned to the exercise group completed
      4 * 45-min moderate-intensity (60%-65% peak oxygen uptake (VO2peak)) arm-crank
      exercise sessions per week. At baseline and follow-up, fasted and postload blood
      samples (collected during oral glucose tolerance tests) were obtained to measure
      metabolic regulation and biomarkers of cardiovascular disease. Abdominal
      subcutaneous adipose tissue biopsies were also obtained, and cardiorespiratory
      fitness was assessed. RESULTS: Compared with CON, INT significantly decreased (P
      = 0.04) serum fasting insulin (Delta, 3.1 +/- 10.7 pmol.L for CON and -12.7 +/-
      18.7 pmol.L for INT) and homeostasis model assessment of insulin resistance
      (HOMA2-IR; Delta, 0.06 +/- 0.20 for CON and -0.23 +/- 0.36 for INT). The exercise
      group also increased VO2peak (Delta, 3.4 mL.kg.min; P <= 0.001). Adipose tissue
      metabolism, composite insulin sensitivity index (C-ISIMatsuda), and other
      cardiovascular disease risk biomarkers were not different between groups.
      CONCLUSIONS: Moderate-intensity upper-body exercise improved aspects of metabolic
      regulation and cardiorespiratory fitness. Changes in fasting insulin and HOMA2
      IR, but not C-ISIMatsuda, suggest improved hepatic but not peripheral insulin
      sensitivity after 6 wk of exercise training in persons with chronic paraplegia.

PMID- 28753162
TI  - Auditory and Audiovisual Close Shadowing in Post-Lingually Deaf Cochlear
      Implanted Patients and Normal-Hearing Elderly Adults.
AB  - OBJECTIVES: The goal of this study was to determine the effect of auditory
      deprivation and age-related speech decline on perceptuo-motor abilities during
      speech processing in post-lingually deaf cochlear-implanted participants and in
      normal-hearing elderly (NHE) participants. DESIGN: A close-shadowing experiment
      was carried out on 10 cochlear-implanted patients and on 10 NHE participants,
      with two groups of normal-hearing young participants as controls. To this end,
      participants had to categorize auditory and audiovisual syllables as quickly as
      possible, either manually or orally. Reaction times and percentages of correct
      responses were compared depending on response modes, stimulus modalities, and
      syllables. RESULTS: Responses of cochlear-implanted subjects were globally slower
      and less accurate than those of both young and elderly normal-hearing people.
      Adding the visual modality was found to enhance performance for cochlear
      implanted patients, whereas no significant effect was obtained for the NHE group.
      Critically, oral responses were faster than manual ones for all groups. In
      addition, for NHE participants, manual responses were more accurate than oral
      responses, as was the case for normal-hearing young participants when presented
      with noisy speech stimuli. CONCLUSIONS: Faster reaction times were observed for
      oral than for manual responses in all groups, suggesting that perceptuo-motor
      relationships were somewhat successfully functional after cochlear implantation
      and remain efficient in the NHE group. These results are in agreement with recent
      perceptuo-motor theories of speech perception. They are also supported by the
      theoretical assumption that implicit motor knowledge and motor representations
      partly constrain auditory speech processing. In this framework, oral responses
      would have been generated at an earlier stage of a sensorimotor loop, whereas
      manual responses would appear late, leading to slower but more accurate
      responses. The difference between oral and manual responses suggests that the
      perceptuo-motor loop is still effective for NHE subjects and also for cochlear
      implanted participants, despite degraded global performance.

PMID- 28753163
TI  - Cortical Processing of Vocal and Nonvocal Sounds in Cochlear-Implanted Children:
      An Electrophysiological Study.
AB  - OBJECTIVES: For prelingually deaf children, cochlear implants (CIs) can restore
      auditory input to the auditory cortex and the ability to acquire spoken language.
      Language development is strongly intertwined with voice perception. The aim of
      this electrophysiological study was to investigate human voice processing using
      measures of cortical auditory evoked potentials (AEPs) in pediatric CI users.
      DESIGN: Cortical AEPs were measured in 8 CI children (4 to 12 years old) with
      good auditory and language performance and 8 normal-hearing (NH) age-matched
      controls. The auditory stimuli were nonspeech vocal sounds (laughing, sighing,
      coughing) and environmental sounds (e.g., telephones, alarms, cars, bells, water,
      wind). Independent component analysis was used to minimize the CI artifact in
      cortical AEPs. RESULTS: Fronto-temporal positivity to vocal sounds was found in
      NH children, with a significant effect in the 140 to 240 msec latency range. In
      CI children, there was a positive response to vocal sounds in the 170 to 250 msec
      latency range, with a more diffuse and anterior distribution than in the NH
      children. CONCLUSIONS: Cortical responses to vocal sounds were recorded in CI
      children. The topography and latency of response to voice differed from that of
      NH children. The results suggest that cortical reorganization for processing
      vocal sounds may occur in congenitally deaf children fitted with a CI.

PMID- 28753164
TI  - Iron deficiency anemia in pregnant women.
AB  - Screening for iron deficiency anemia (IDA) in all pregnant women is recommended.
      IDA is a prevalent cause of nutritional deficiency anemia, and oral iron is the
      first line of treatment. Other treatments include parenteral iron or blood
      transfusion(s). Untreated IDA in pregnancy can result in complications for the
      mother and fetus.

PMID- 28753165
TI  - Pediatric rheumatologic diseases: A review for primary care NPs.
AB  - Rheumatologic diseases are uncommon in children but have the potential for
      significant morbidity, mortality, and disability. This article reviews the most
      common rheumatologic diseases in children, their diagnostic evaluations, and the
      NP's role in the management and coordination of these conditions.

PMID- 28753166
TI  - Comparison Between the Cobra Perilaryngeal Airway and Laryngeal Mask Airways
      Under General Anesthesia: A Systematic Review and Meta-analysis.
AB  - The complication rate and efficacy of the Cobra Perilaryngeal Airway (CobraPLA)
      and laryngeal mask airways (LMAs(r)) have been evaluated in the published
      literature, but the conclusions have been inconsistent. The aim of this
      systematic review and meta-analysis was thus to assess the performance of the
      CobraPLA and LMAs under general anesthesia. We searched PubMed, Embase, and the
      Cochrane Library for randomized controlled trials comparing the CobraPLA with
      LMAs under general anesthesia. The LMAs used for comparison were the classic LMA
      (CLMA) and the unique LMA (ULMA). The random effect model was used if
      heterogeneity was observed, otherwise the fixed effect model was used. Seventeen
      randomized controlled trials were included; number of studies analyzed for each
      result are different and were up to 10. The current result suggests that no
      significant difference between the devices in the insertion success rate at the
      first attempt. The success rate of first insertion of the CobraPLA was not
      different from the rates for the CLMA and the ULMA (relative risk: 0.95, 95%
      confidence interval [CI], 0.91-1.00). CobraPLA insertion was not different from
      CLMA and ULMA insertion. The CobraPLA provided an oropharyngeal leak pressure
      higher than that provided by the CLMA (weight mean difference: 3.90, 95% CI,
      [1.59-6.21] cmH2O) and ULMA (weight mean difference: 6.57, 95% CI, [4.30-8.84]
      cmH2O). We also found a higher likelihood of blood staining in the airway with
      the CobraPLA than with the CLMA. In our research, the principal finding of our
      meta-analysis is that the success rate of first insertion of the CobraPLA was not
      different from the rate for each of the CLMA and the ULMA, which featured a short
      learning curve implying its ease of insertion. There was also no significant
      difference in the incidence of the best view (with a score of 4) obtained with
      the CobraPLA compared with the other 2 devices. The CobraPLA does seem to be
      superior to the CLMA and ULMA in providing a higher oropharyngeal leak pressure.
      The data were insufficient to establish differences in airway adverse events
      between the groups except for blood staining in the devices, although mucosal
      trauma occurred more frequently with the Cobra PLA device than with the CLMA and
      the ULMA.

PMID- 28753167
TI  - Informed Consent and Nitrous Oxide for Obstetric Analgesia.

PMID- 28753168
TI  - In Response.

PMID- 28753169
TI  - Absolute Postoperative B-Type Natriuretic Peptide Concentrations, but Not Their
      General Trend, Are Associated With 12-Month, All-Cause Mortality After On-Pump
      Cardiac Surgery.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is a predictor of mortality after on
      pump cardiac surgery. However, previous limited and heterogeneous studies have
      focused on peak concentrations at 3 to 5 days after surgery and may not offer
      clinicians much help in early decision-making. After confirming the predictive
      value of first-postoperative-day BNP in a preliminary analysis, we explored the
      association between isolated second-postoperative-day BNP concentrations, second
      day BNP concentrations in conjunction with first-day BNP concentrations, and the
      change in BNP (ie, DeltaBNP) from the first to the second postoperative day and
      12-month, all-cause mortality. METHODS: We included consecutive patients
      undergoing on-pump cardiac surgery in this observational, secondary analysis of
      prospectively collected data. We analyzed biomarkers on the first and second
      postoperative day. DeltaBNP was defined as BNP on the second postoperative day
      minus BNP on the first postoperative day. The primary end point was 12-month, all
      cause mortality. The secondary end point was a composite of major adverse cardiac
      events (MACEs) at 12 months and/or all-cause mortality at 12 months. MACE was
      defined as nonfatal cardiac arrest, myocardial infarction, and congestive heart
      failure. The association between BNP and outcomes was examined by receiver
      operating characteristic curves, as well as univariate and multivariable logistic
      regression, adjusting for the EuroSCORE II, cross-clamp time, and first
      postoperative-day troponin T. RESULTS: We included 1199 patients in the
      preliminary analysis focused on BNP on postoperative day 1. In the analyses
      examining BNP variables requiring second-postoperative-day BNP measurement (n =
      708), we observed 66 (9.3%) deaths, 48 (6.8%) MACE, and 104 (14.7%) deaths and/or
      MACE. Both first- and second-postoperative-day BNP were significant independent
      predictors of all-cause, 12-month mortality per 100 ng/L increase (adjusted odds
      ratio [aOR], 1.040 [95% confidence interval (CI), 1.019-1.065] and 1.064 [95% CI,
      1.031-1.105], respectively). When used in conjunction with one another, first-day
      BNP was not significant (aOR, 1.021 [95% CI, 0.995-1.048]), while second-day BNP
      remained significant (aOR, 1.046 [95% CI, 1.008-1.091]). The DeltaBNP per 100
      ng/L increase was not associated with 12-month, all-cause mortality in the
      univariable (OR, 0.977 [95% CI, 0.951-1.007]) or multivariable analysis (aOR,
      0.989 [95% CI, 0.962-1.021]). CONCLUSIONS: Both absolute concentrations of first-
      and second-postoperative-day BNP are independent predictors of 12-month, all
      cause mortality. When modeled together, second-postoperative-day BNP is more
      predictive of 12-month, all-cause mortality. Although intuitively appealing, the
      change in BNP from the first to the second postoperative day is a complex
      variable and should not routinely be used for prognostication.

PMID- 28753170
TI  - Antibiotics and the Anesthesiologist: Is There a "Consensus?"

PMID- 28753171
TI  - Informed Consent and Nitrous Oxide for Labor Analgesia.

PMID- 28753172
TI  - Antifragile Systems and Physician Wellness.

PMID- 28753174
TI  - On Depression.

PMID- 28753173
TI  - The WFSA Global Anesthesia Workforce Survey.
AB  - BACKGROUND: Safe anesthesia and surgical care are not available when needed for 5
      billion of the world's 7 billion people. There are major deficiencies in the
      specialist surgical workforce in many parts of the world, and specific data on
      the anesthesia workforce are lacking. METHODS: The World Federation of Societies
      of Anaesthesiologists conducted a workforce survey during 2015 and 2016. The aim
      of the survey was to collect detailed information on physician anesthesia
      provider (PAP) and non-physician anesthesia provider (NPAP) numbers,
      distribution, and training. Data were categorized according to World Health
      Organization regional groups and World Bank income groups. RESULTS: We obtained
      information for 153 of 197 countries, representing 97.5% of the world's
      population. There were marked differences in the density of PAPs between World
      Health Organization regions and between World Bank income groups, ranging from 0
      to over 20 PAP per 100,000 population. Seventy-seven countries reported a PAP
      density of <5, with particularly low densities in the African and South-East Asia
      regions. NPAPs make up a large part of the global anesthesia workforce,
      especially in countries with limited resources. Even when NPAPs are included, 70
      countries had a total anesthesia provider density of <5 per 100,000. Using
      current population data, over 136,000 additional PAPs would be needed immediately
      to achieve a minimum density of 5 per 100,000 population in all countries.
      CONCLUSIONS: The World Federation of Societies of Anaesthesiologists Global
      Anesthesia Workforce Survey is the most comprehensive study of the global
      anesthesia workforce to date. It is the first step in a process of ongoing data
      collection and longitudinal follow-up. The authors recommend an interim goal of
      at least 5 specialist physician anesthesia providers (anesthesiologists) per
      100,000 population. A marked increase in training of PAPs and NPAPs will need to
      occur if we are to have any hope of achieving safe anesthesia for all by 2030.

PMID- 28753175
TI  - Poor Agreement Between Imaging and Histologic and Colonoscopy Findings in
      Pediatric Patients.
AB  - BACKGROUND: Computed tomography scans (CTs), more recently magnetic resonance
      imaging, are often used to assess the gastrointestinal tract in patients
      complaining of abdominal pain. We aim to determine the strength of agreement
      among abdominal imaging, endoscopic, and histologic findings. METHODS:
      Retrospective chart review of pediatric patients who underwent colonoscopy
      between January 1, 2012, and December 31, 2014, at Women and Children's Hospital
      of Buffalo. Patients who had abdominal and pelvic CTs or magnetic resonance
      imaging within 30 days before or after a colonoscopy were included. RESULTS: One
      hundred two patients were included: mean age 12.7 +/- 3.8 years, 66% girls. A
      total of 109 imaging studies were performed. Overall 61% of imaging studies were
      abnormal. The most frequent intestinal radiological findings were colonic wall
      thickening (CWT) (55%) and colonic wall enhancement (CWH) (24%). Free fluid (20%)
      and fat stranding (18%) were the most common extra-intestinal findings. Imaging
      studies agreed with histology in 81% and with colonoscopy in 75% with a moderate
      strength of agreement (k: 0.59 and 0.466, respectively). CWT agreed with
      histology in 74% with a moderate strength of agreement (k: 0.47). History of
      weight loss (OR 5.35, P = 0.041), chronic diarrhea (OR 4.22, P = 0.014), a
      positive lactoferrin (OR 7.00, P = 0.011), and presence of CWT on imaging study
      (OR 5.20, P = 0.001) were predictive of having abnormal histology. CONCLUSIONS:
      The strength of agreement among imaging, endoscopic, and histologic findings was
      suboptimal. Colonoscopy and imaging are both likely to be necessary in patients
      with suspected inflammatory bowel disease. Although colonoscopy may be superior
      in diagnosis of colitis, imaging may provide more information regarding small
      bowel disease.

PMID- 28753176
TI  - Cystic Fibrosis-related Liver Disease: Research Challenges and Future
      Perspectives.
AB  - OBJECTIVES: Hepatobiliary complications are a leading cause of morbidity and
      mortality in cystic fibrosis (CF) patients. Knowledge of the underlying
      pathological aspects and optimal clinical management is, however, sorely lacking.
      METHODS: We provide a summary of the lectures given by international speakers at
      the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition
      (ESPGHAN) monothematic conference on cystic fibrosis-related liver disease (CFLD)
      held in Paris in January 2016, to discuss the status of our current knowledge of
      liver disease in CF patients, to define the critical areas that need to be
      addressed, and to resolve actions to elucidate relevant mechanisms of disease to
      optimise future therapeutic options. CONCLUSIONS: The need for a universal
      consensus on the definition of CFLD to clarify disease stage and to identify
      relevant biomarkers to assess disease severity was highlighted. A deeper
      understanding of the pathophysiology and prognostic factors for the long-term
      evolution of CFLD is fundamental to move forward and has a strong bearing on
      identifying potential treatments. Novel experimental models and new treatment
      options under investigation are discussed and offer hope for the near future of
      CFLD.

PMID- 28753177
TI  - Assessing the Transition Intervention Needs of Young Adults With Inflammatory
      Bowel Diseases.
AB  - OBJECTIVES: The transition of inflammatory bowel disease (IBD) patients from
      pediatric to adult care can be challenging. Developing an effective transition
      intervention requires assessing the current transition experience for potential
      improvements, determining preferred content and format, and assessing patients'
      transition skills. METHODS: This mixed-methods study of 20 transitioned IBD
      patients (ages 17-20 years) used semistructured interviews and validated
      assessments of self-management/self-advocacy and IBD knowledge. Interviews were
      analyzed thematically. Assessment scores were compared with published reference
      data by estimating proportion or mean differences and 95% confidence intervals
      (CIs). RESULTS: The concept of a transition intervention was well-received by
      participants. Preferred content centered on medications, disease and what to
      expect. Preferred ways to acquire knowledge were one-on-one instruction,
      handouts, and websites. Identified themes were "individualized and multifaceted,"
      "teach about transition," and "support the shift in responsibility." Among
      participants, 95% did not achieve 90% mastery of transition skills (0.6% higher
      [95% CI -10.7% to 9.5%] than the reference estimate) and the mean knowledge score
      was 15.15 (3.86 [95% CI 2.27 to 5.45] points higher than the reference estimate).
      CONCLUSIONS: We have identified preferred intervention formats and content as
      well as skill areas to target for improvement. As a result of this work, we will
      design a website intervention pertaining to identified themes.

PMID- 28753178
TI  - Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study.
AB  - OBJECTIVE: Cesarean section (C-section) is associated with various immune
      mediated diseases in the offspring. We investigated the relationship between mode
      of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational
      birth cohort. METHODS: From 2004 to 2010, infants from the general population who
      tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental
      Determinants for Diabetes in the Young (TEDDY) study. Children were annually
      screened for transglutaminase autoantibodies, if positive, they are retested
      after 3 to 6 months and those persistently positive defined as CDA. Associations
      of C-section with maternal (age, education level, parity, pre-pregnancy weight,
      diabetes, smoking, weight gain during pregnancy) and child characteristics
      (gestational age, birth weight) were examined by Fisher exact test or Wilcoxon
      rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox
      proportional hazard regression models. RESULTS: Of 6087 analyzed singletons, 1600
      (26%) were born by C-section (Germany 38%, United States 37%, Finland 18%, Sweden
      16%), and the remaining were born vaginally without instrumental support; 979
      (16%) had developed CDA and 343 (6%) developed CD. C-section was associated with
      lower risk for CDA (hazard ratio [HR] = 0.85; 95% confidence interval [CI] 0.73,
      0.99 P = 0.032) and CD (HR = 0.75; 95% CI 0.58, 0.98; P = 0.034). After adjusting
      for country, sex, HLA-genotype, CD in family, maternal education, and breast
      feeding duration, significance was lost for CDA (HR = 0.91; 95% CI 0.78, 1.06; P
      = 0.20) and CD (HR = 0.85; 95% CI 0.65, 1.11; P = 0.24). Presurgical ruptured
      membranes had no influence on CDA or CD development. CONCLUSION: C-section is not
      associated with increased risk for CDA or CD in the offspring.

PMID- 28753179
TI  - Intervention for Feeding Difficulties in Children With a Complex Medical History:
      A Randomized Clinical Trial.
AB  - OBJECTIVE: This study aimed to compare outcomes of different multidisciplinary
      feeding therapy approaches in children with feeding difficulties. METHODS:
      Children aged 2 to 6 years with feeding difficulties and a medically complex
      history (MC) were recruited. Children with feeding difficulties and a
      nonmedically complex history (NMC) were included as a comparison group.
      Participants attended a clinical assessment, and eligible participants were
      randomized to receive targeted feeding intervention incorporating either operant
      conditioning or systematic desensitization. Parents could elect to receive
      intervention in an intensive (10 sessions in a week) or weekly (10 sessions
      during 10 weeks) format. Both groups received immersive parent training. A review
      was completed 3 months post-intervention. RESULTS: In total, 98 participants were
      eligible to participate (MC, n = 43; NMC, n = 55). Data from 20 children from the
      MC group (47%) and 41 children from the NMC group (75%) were included in the
      final analysis. Clinically significant improvements were observed following both
      arms of therapy, consistent with previous research. Parents of children in the MC
      arm were significantly more likely to elect for intensive intervention than
      weekly (MC = 12/20, 60%; 12/41, 29%; P = 0.02). CONCLUSIONS: Both therapy
      protocols were considered clinically effective. The difference in attrition rates
      between the etiological groups suggests primary differences in how service
      delivery should be managed. Progress for the medically complex child may be
      slower while medical issues are stabilized, or while the focus for parents shifts
      to other developmental areas. In planning services for a medically complex group,
      therefore, it is essential that consideration be given to medical and family
      needs.

PMID- 28753180
TI  - Mass Screening for Celiac Disease Among School-aged Children: Toward Exploring
      Celiac Iceberg in Saudi Arabia.
AB  - OBJECTIVES: We conducted this mass screening study to determine the prevalence of
      celiac disease (CD) and characterize the celiac iceberg among Saudi pediatric
      population in Riyadh, the capital city of Saudi Arabia. METHODS: During the study
      period (January 2014-June 2016), we have conducted a cross-sectional, mass
      screening, immunoglobulin A-tissue transglutaminase (TTG-IgA)-based study on 7930
      Saudi students from primary and intermediate schools in Riyadh. Students with
      positive TTG-IgA (>20 U/L) were called in the hospital to undergo a repeat of TTG
      IgA; in those with borderline positive TTG-IgA (20-60 U/L), IgA-endomyseal
      antibody (EMA-IgA) test was performed. Children with TTG-IgA >60 U/L and children
      with borderline positive TTG-IgA and positive EMA-IgA were advised to undergo
      upper endoscopy and intestinal biopsies. RESULTS: We identified 221 students with
      positive TTG-IgA (2.8%). CD was diagnosed in 119 cases (1.5%, 1:67 Saudi
      children) (mean age 11.5 +/- 2.62 years; girls 81 [68%]). Another 51 children had
      persistently borderline positive TTG-IgA but negative EMA (0.64%) and the
      remaining 51 had transiently positive TTG-IgA. We have identified 3 clinical
      patterns in the screening-identified cases with CD: a silent form (37%), a mild
      symptomatic form characterized by gastrointestinal symptoms in presence of normal
      growth or overweight/obesity (48%), and gastrointestinal symptoms associated with
      impaired growth in 15%. CONCLUSIONS: Our study provided evidence of a high
      prevalence of CD among Saudi children (1.5%), a rate that is at least twice the
      average prevalence rate in Europe and North America.

PMID- 28753181
TI  - Real-Life Anti-Tumour Necrosis Factor Experience in > 500 Paediatric United
      Kingdom Inflammatory Bowel Disease Patients.
AB  - OBJECTIVES: To measure the effectiveness, safety and use of anti-Tumour necrosis
      Factor (TNF) therapy in paediatric inflammatory bowel disease (PIBD) in the
      United Kingdom (UK). METHODS: Prospective UK audit of patients newly starting
      anti-TNF therapy. Disease severity was assessed using Physician Global Assessment
      (PGA) +/or the Paediatric Crohn's Disease Activity Index (PCDAI). RESULTS: 37
      centres participated (23 of 25 specialist PIBD sites). 524 patients were
      included; 429 Crohn's disease (CD), 76 ulcerative colitis (UC), 19 IBD
      unclassified (IBDU). 87% (488/562) anti-TNF was infliximab; commonest indication
      was active luminal CD 77% (330/429) or chronic refractory UC/IBDU 56% (53/95);
      79% (445/562) had concomitant co-immunosuppression. In CD (267/429 male), median
      time from diagnosis to treatment was 1.42 years (IQR 0.63-2.97). Disease (at
      initiation) was moderate or severe in 91% (156/171) by PGA compared to 41%
      (88/217) by PCDAI; Kappa (Kappa) 0.28 = only 'fair agreement' (p < 0.001).Where
      documented, 77% (53/69) of CD patients responded to induction; and 65% (46/71)
      entered remission. 2287 infusions and 301.96 years of patient follow-up (n = 385)
      are represented; adverse events affected 3% (49/1587) infliximab and 2% (2/98)
      adalimumab infusions (no deaths or malignancies). Perianal abscess drainage was
      less common after anti-TNF initiation (CD): 26% (27/102) before, 7% (3/42) after
      (p = 0.01); however pre and post anti-TNF data collection was not over equal time
      periods. CONCLUSION: Anti-TNFs are effective treatments, usually given with
      thiopurine co-immunosuppression. This study highlights deficiencies in formal
      documentation of effect and disparity between disease severity scoring tools
      which need to be addressed to improve ongoing patient care.

PMID- 28753182
TI  - Early Onset of Wilson Disease: Diagnostic Challenges.
AB  - OBJECTIVES: The aim of the study was to analyze the clinical presentations,
      diagnosis, and treatment of patients ages <=5 years with early onset Wilson
      disease (WD). METHODS: Data from 143 pediatric patients with WD treated at our
      center between January 1996 and November 2015 were retrospectively analyzed.
      RESULTS: A review of the 143 pediatric patients with WD identified 21 (10 girls,
      11 boys) with first symptoms or abnormal liver function test results at age <=5
      years. The diagnosis of WD was confirmed in 8 patients younger than 5 years. At
      baseline the mean serum alanine aminotransferase level was 222 U/L and the mean
      serum aspartate aminotransferase level was 130 U/L. The mean serum ceruloplasmin
      concentration in 16 tested patients was <20 mg/dL. Of the 15 patients who
      underwent urinary copper excretion testing, 8 had levels between 40 and 100
      MUg/day, with only 4 having levels >100 MUg/day. Liver copper quantification was
      >250 MUg/g dry weight in 16 patients. The most common mutation was p.H1069Q, with
      compound heterozygosity in 5 patients and homozygosity in 9. Sixteen patients
      were treated with zinc salts and 5 with D-penicillamine. Both treatments were
      effective, with no serious side effects observed after 3 to 24 months.
      CONCLUSIONS: WD can present as early as 2 years of age. Because biochemical tests
      may be less sensitive in very young children, diagnoses may require a combination
      of tests. If molecular tests are inconclusive, liver copper content should be
      measured.

PMID- 28753183
TI  - Serum n-6 and n-9 Fatty Acids Correlate With Serum IGF-1 and Growth Up to 4
      Months of Age in Healthy Infants.
AB  - OBJECTIVE: The aim of this study was to study the relationship between insulin
      like growth factor-1 (IGF-1), serum phospholipid fatty acids, and growth in
      healthy full-term newborns during infancy. METHODS: Prospective observational
      study of a population-based Swedish cohort comprising 126 healthy, term infants
      investigating cord blood and serum at 2 days and 4 months of age for IGF-1 and
      phospholipid fatty acid profile and breast milk for fatty acids at 2 days and 4
      months, compared with anthropometric measurements (standard deviation scores).
      RESULTS: At all time-points arachidonic acid (AA) was negatively associated with
      IGF-1. IGF-1 had positive associations with linoleic acid (LA) at 2 days and 4
      months and mead acid (MA) showed positive associations in cord blood. Multiple
      regression analyses adjusted for maternal factors (body mass index, weight gain,
      smoking, education), sex, birth weight and feeding modality confirmed a negative
      association for the ratio AA/LA to IGF-1. MA in cord blood correlated to birth
      size. Changes in the ratios of n-6/n-3 and AA/docosahexaenoic acid from day 2 to
      4 months together with infants' weight and feeding modality determined 55% of the
      variability of delta-IGF-1. Breast-fed infants at 4 months had lower IGF-1
      correlating with lower LA and higher AA concentrations, which in girls correlated
      with lower weight gain from birth to 4 months of age. CONCLUSIONS: Our data
      showed interaction of n-6 fatty acids with IGF-1 during the first 4 months of
      life, and an association between MA and birth size when adjusted for confounding
      factors. Further follow-up may indicate whether these correlations are associated
      with later body composition.

PMID- 28753184
TI  - Radiation Exposure and Attributable Cancer Risk in Patients With Esophageal
      Atresia.
AB  - OBJECTIVES: Cases of esophageal carcinoma have been documented in survivors of
      esophageal atresia (EA). Children with EA undergo considerable amounts of
      diagnostic imaging and consequent radiation exposure potentially increasing their
      lifetime cancer mortality risk. This study evaluates the radiological procedures
      performed on patients with EA and estimates their cumulative radiation exposure
      and attributable lifetime cancer mortality risk. METHODS: Medical records of
      patients with EA managed at a tertiary care center were reviewed for
      demographics, EA subtype, and number and type of radiological investigations.
      Existing normative data were used to estimate the cumulative radiation exposure
      and lifetime cancer risk per patient. RESULTS: The present study included 53
      patients with a mean follow-up of 5.7 years. The overall median and maximum
      estimated effective radiation dose in the neonatal period was 5521.4 MUSv/patient
      and 66638.6 MUSv/patient, respectively. This correlates to a median and maximum
      estimated cumulative lifetime cancer mortality risk of 1:1530 and 1:130,
      respectively. Hence, radiation exposure in the neonatal period increased the
      cumulative cancer mortality risk a median of 130-fold and a maximum of 1575-fold
      in EA survivors. CONCLUSIONS: Children with EA are exposed to significant amounts
      of radiation and an increased estimated cumulative cancer mortality risk. Efforts
      should be made to eliminate superfluous imaging.

PMID- 28753185
TI  - Pediatric Gastroesophageal Reflux Disease: Systematic Review on Prognosis and
      Prognostic Factors.
AB  - In this systematic review, we summarize the evidence on prognosis and prognostic
      factors of pediatric gastroesophageal reflux disease (GERD). A structured search
      of Embase and MEDLINE/PubMed (inception to April 2016) yielded 5365 references; 4
      publications met our inclusion criteria (risk of bias moderate-high). Definitions
      and outcome measures varied widely between studies. The percentage of children
      with a diagnosis of GERD with esophagitis that had persisting symptoms and/or
      were on antireflux medication at follow-up (12 months to >5 years) ranged from
      23% (weekly symptoms) to 68% (antireflux medication), depending on definition
      used. In children with a diagnosis of GERD without esophagitis, 1.4% developed
      esophagitis at follow-up (>5 years); none developed Barrett esophagus. In
      conclusion, prognostic studies on pediatric GERD are of limited quality and show
      large methodological heterogeneity. Based on these studies, we are unable to
      identify those children at risk for unfavorable outcome with regards to GERD
      symptoms or endoscopic complications.

PMID- 28753186
TI  - Bioactive Whey Protein Concentrate and Lactose Stimulate Gut Function in Formula
      fed Preterm Pigs.
AB  - OBJECTIVE: Formula feeding is associated with compromised intestinal health in
      preterm neonates compared with maternal milk, but the mechanisms behind this are
      unclear. We hypothesized that the use of maltodextrin and whey protein
      concentrates (WPCs) with reduced bioactivity owing to thermal processing are
      important factors. METHOD: Ninety-two cesarean-delivered preterm pigs were fed
      increasing doses of formulas for 5 days (24-120 mL . kg . day). In experiment 1,
      4 groups of pigs (n = 15-16) were fed lactose- or maltodextrin-dominant formulas
      (lactose/maltodextrin ratios 3:1 or 1:3, respectively), containing WPC with
      either high or low levels of IgG (WPC1 or WPC2, respectively). In experiment 2, 2
      groups of pigs (n = 15-16) were fed lactose-dominant formulas with either a
      bioactive WPC (BioWPC, produced by reduced thermal-processing) or a conventional
      WPC (ConWPC). RESULTS: In experiment 1, pigs fed formula with WPC1 had higher
      villi, hexose absorption, and lactase activity in small intestine, relative to
      WPC2, but predominantly with the lactose-dominant formula (all P < 0.05). In
      experiment 2, the BioWPC product had higher bioactivity, as indicated by higher
      IgG, lactoferrin, and TGF-beta2 levels, and better enterocyte proliferation in
      vitro. Pigs fed the BioWPC formula showed better feeding tolerance and higher
      intestinal villi and lactase activity (all P < 0.05). The BioWPC formula-fed pigs
      also had greater physical activity (P < 0.05 on day 4) and tended to show
      improved hexose absorption and decreased gut permeability (both P <= 0.09).
      CONCLUSIONS: Infant formulas containing lactose as the main carbohydrate, and WPC
      with reduced thermal processing, may support gut maturation and health in
      sensitive, preterm neonates.

PMID- 28753187
TI  - SLC5A1 Mutations in Saudi Arabian Patients With Congenital Glucose-Galactose
      Malabsorption.
AB  - Congenital glucose-galactose malabsorption (cGGM) is a rare autosomal recessive
      disorder, caused by mutations in the SLC5A1 gene, encoding the sodium/glucose
      cotransporter 1, which may result in severe life-threatening osmotic diarrhea due
      to the accumulation of unabsorbed sugars in the intestinal lumen. If treated
      early with elimination of glucose and galactose from the diet, patients usually
      recover and develop normally. We present clinical and molecular data from 16
      unrelated cGGM diagnosed Saudi patients from consanguineous families with
      majority of them having previous positive family history of cGGM. Sanger
      sequencing for the full coding regions of SLC5A1 for all patients resulted in the
      identification of 4 allelic variants in a homozygous state. Two mutations are
      novel; c.265G>A (p.G89R) and c.1304 G>A (p.G435D), and 2 have been previously
      reported to cause cGGM, c.765 C>G (p.C255W) and c.1136 G>A (p.R379Q). This is the
      first report delineating the clinical and molecular basis of cGGM in patients
      from this region.

PMID- 28753189
TI  - Commentary to Article Entitled "Vitamin D Deficiency Is Not Associated With
      Growth or the Incidence of Common Morbidities Among Tanzanian Infants".

PMID- 28753188
TI  - The Relationship Between Child Mortality Rates and Prevalence of Celiac Disease.
AB  - OBJECTIVES: Some evidence suggests that prevalence of celiac disease in the
      general population is increasing over time. Because the prognosis of celiac
      disease was a dismal one before discovering the role of gluten, our aim was to
      investigate a possible relationship between children under-5 mortality rates and
      prevalence rates of celiac disease. METHODS: Thanks to a literature review, we
      found 27 studies performed in 17 different countries describing the prevalence of
      celiac disease in schoolchildren; between 1995 and 2011, 4 studies were performed
      in Italy. A meta-analysis of prevalence rates was performed. Prevalence was
      compared between specific country under-5 mortality groups, publication year, and
      age. RESULTS: In the last decades, under-5 mortality rates have been decreasing
      all over the world. This reduction is paralleled by an increase of the prevalence
      of celiac disease. The Spearman correlation coefficient was -63%, 95% confidence
      interval -82% to -33% (P < 0.001). So, the higher the mortality rate, the lower
      the prevalence of CD. This finding is confirmed by the meta-analysis of the 4
      studies conducted in Italy over time. CONCLUSIONS: The under-5 mortality rate
      seems to influence the prevalence of celiac disease in the general population. In
      the near future, the number of patients with celiac disease will increase, thanks
      to the better environmental conditions that nowadays allow a better survival of
      children with celiac disease.

PMID- 28753190
TI  - New Celiac Icebergs Are Spotted, Other Are Slowly Emerging.

PMID- 28753191
TI  - The Patient-Healthcare Professional Relationship and Communication in the
      Oncology Outpatient Setting: A Systematic Review.
AB  - BACKGROUND: Today, cancer care and treatment primarily take place in an
      outpatient setting where encounters between patients and healthcare professionals
      are often brief. OBJECTIVE: The aim of this study was to summarize the literature
      of adult patients' experiences of and need for relationships and communication
      with healthcare professionals during chemotherapy in the oncology outpatient
      setting. METHODS: The systematic literature review was carried out according to
      PRISMA guidelines and the PICO framework, and a systematic search was conducted
      in MEDLINE, CINAHL, The Cochrane Library, and Joanna Briggs Institute Evidence
      Based Practice Database. RESULTS: Nine studies were included, qualitative (n = 5)
      and quantitative (n = 4). The studies identified that the relationship between
      patients and healthcare professionals was important for the patients' ability to
      cope with cancer and has an impact on satisfaction of care, that hope and
      positivity are both a need and a strategy for patients with cancer and were
      facilitated by healthcare professionals, and that outpatient clinic visits framed
      and influenced communication and relationships. CONCLUSIONS: The relationship and
      communication between patients and healthcare professionals in the outpatient
      setting were important for the patients' ability to cope with cancer.
      IMPLICATIONS FOR PRACTICE: Healthcare professionals need to pay special attention
      to the relational aspects of communication in an outpatient clinic because
      encounters are often brief. More research is needed to investigate the type of
      interaction and intervention that would be the most effective in supporting adult
      patients' coping during chemotherapy in an outpatient clinic.

PMID- 28753192
TI  - Interventions Using Social Media for Cancer Prevention and Management: A
      Systematic Review.
AB  - BACKGROUND: Regarding cancer awareness, social media effectively promotes health
      and supports self-management. Given the diverse study designs, methodologies, and
      approaches of social media interventions in oncology, it is difficult to
      determine the effects of social media on cancer prevention and management.
      OBJECTIVE: We aim to systematically review intervention studies using social
      media for cancer care. METHODS: A systematic search, using 7 electronic databases
      (PubMed, Web of Science, CINAHL, Cochrane Library, Scopus, EMBASE, and PsycINFO),
      was conducted to identify surveys and interventions using contemporary social
      media tools with a focus on cancer. RESULTS: Of the 18 selected studies, 7 were
      randomized controlled trials. Most studies were conducted for all types of
      cancer, and some were conducted for breast cancer in the United States, with
      mostly white female participants. Facebook was the most frequently used platform.
      Most studies targeted healthy participants providing cancer prevention education.
      With social media platforms as part of a larger intervention, or the main
      component of interventions, interventions were overall feasible and showed a
      significant improvement in cancer prevention and management. CONCLUSIONS: Social
      media tools have the potential to be effective in delivering interventions for
      cancer prevention and management. However, there was a dearth of studies with
      rigorous study methodologies to test social media effects on various cancer
      related clinical outcomes. IMPLICATIONS FOR PRACTICE: Social media use in cancer
      care will facilitate improved communication and support among patients,
      caregivers, and clinicians and, ultimately, improved patient care. Clinicians
      need to carefully harness social media to enhance patient care and clinical
      outcomes.

PMID- 28753193
TI  - Gender Difference in Cancer Patients' Adherence to Analgesics and Related
      Outcomes of Pain Management.
AB  - BACKGROUND: Males and females have significant differences in certain medical
      outcomes. However, little research has explored the gender differences in cancer
      patient perceptions of analgesics, the relationship between gender and analgesic
      adherence, or the effectiveness of pain management. OBJECTIVE: The objectives of
      this study were to compare gender differences associated with hesitancy to use
      analgesics, analgesic adherence, or pain management effectiveness and to examine
      whether gender can precisely predict analgesic adherence. METHODS: The study was
      conducted in the outpatient oncology department of a medical center in Taiwan. A
      descriptive and cross-sectional design was used. The study samples were collected
      from 362 cancer patients. The participants completed the short version of the
      Barriers Questionnaire-Taiwan, the Morisky Analgesics Adherence Measure-Taiwan
      version, the Brief Pain Inventory-Chinese version, the Pain Management Index, and
      a demographic and disease questionnaire. RESULTS: The pain intensity and
      hesitancy to use analgesics scores were significantly higher among females than
      among males. The Pain Management Index results indicated that a larger percentage
      of males had adequate pain management. In addition, being male was a significant
      predictor of higher analgesic adherence (odds ratio, 1.93; P < .05). CONCLUSIONS:
      Gender could precisely predict cancer patients' medication adherence. Women
      experienced significantly greater pain than did men but also had more hesitancy
      to use analgesics, lower adherence, and inadequate pain management. IMPLICATIONS
      FOR PRACTICE: Healthcare professionals should consider women as a high-risk group
      for inadequate pain control. It is crucial for health providers to consider the
      gender discrepancy when attempting to improve cancer pain management.

PMID- 28753194
TI  - Pilot Study of a Communication Coaching Telephone Intervention for Lung Cancer
      Caregivers.
AB  - BACKGROUND: Family caregivers are a key communication source for nurses, and
      there is a need to provide communication skill building for caregivers.
      OBJECTIVE: A pilot study was conducted to determine feasibility and use of a
      communication coaching telephone intervention aimed at improving caregiver
      confidence in communication and reducing psychological distress. METHODS: A
      printed communication guide for caregivers and a 1-time communication coaching
      call delivered by a research nurse were provided to caregivers. Recruitment and
      attrition, implementation and content of coaching calls, caregiver outcomes, and
      satisfaction with intervention were analyzed. RESULTS: Twenty caregivers were
      recruited across 4 cohorts-diagnosis, treatment, survivorship, and end of life
      with recruitment greater than 70%. Caregiver calls averaged 37 minutes, and most
      caregivers reported communication challenges with family members. Caregiver
      action plans revealed a need to develop communication skills to ask for help and
      share information. Caregivers reported satisfaction with the print guide, and 90%
      of caregivers followed through with their action plan, with 80% reporting that
      the action plan worked. Caregiver confidence in communication with healthcare
      providers was improved, except for caregivers of cancer survivors. CONCLUSIONS:
      Recruitment and attrition rates demonstrate feasibility of the intervention.
      Caregivers reported that the communication coaching telephone intervention was
      considered valuable and they were able to implement a communication action plan
      with others. IMPLICATIONS FOR PRACTICE: Lessons were learned about intervention
      content, namely, that nurses can help caregivers learn communication strategies
      for asking for help, sharing cancer information, and initiating self-care.

PMID- 28753196
TI  - Prognostic Classification System for Implant Recession Defects.
AB  - PURPOSE: The etiology and progression of periimplant mucogingival defects are
      multifactorial. As such, the aim of this study was to discern and discuss the key
      long-term prognostic factors that change the balance of homeostasis/regeneration
      in periimplant mucogingival and recession defects. MATERIALS AND METHODS: This
      report provides cases and a discussion of anatomical factors that affect the long
      term maintenance of periimplant soft tissue. RESULTS: The factors guiding long
      term maintenance of the periimplant soft tissue apparatus are increasingly
      complex due to the additive combination of patient-related factors, anatomical
      variations, and unique material-host interactions. CONCLUSIONS: Severity and
      number of these contributing factors should be considered before implant
      placement and/or in the treatment of periimplant defects to achieve the best
      esthetic and functional outcome. In addition, assessment of prognostic factors
      should be used to provide the patient a realistic, long-term assessment of the
      esthetic and functional stability of both implant and the surrounding periimplant
      tissues.

PMID- 28753197
TI  - Corrigendum: Low-dose add-on memantine treatment may improve cognitive
      performance and self-reported health conditions in opioid-dependent patients
      undergoing methadone-maintenance-therapy.
AB  - This corrects the article DOI: 10.1038/srep09708.

PMID- 28753198
TI  - Erratum: Donor-derived exosomes induce specific regulatory T cells to suppress
      immune inflammation in the allograft heart.
AB  - This corrects the article DOI: 10.1038/srep20077.

PMID- 28753199
TI  - Erratum: Capturing the wide variety of impaired fracture healing phenotypes in
      Neurofibromatosis Type 1 with eight key factors: a computational study.
AB  - This corrects the article DOI: 10.1038/srep20010.

PMID- 28753200
TI  - Erratum: At least two Fc Neu5Gc residues of monoclonal antibodies are required
      for binding to anti-Neu5Gc antibody.
AB  - This corrects the article DOI: 10.1038/srep20029.

PMID- 28753201
TI  - Delivery of human erythropoietin gene with an adeno-associated virus vector
      through parotid glands to treat renal anaemia in a swine model.
AB  - Anaemia is a common complication of chronic kidney disease, for which there is
      presently no adequate treatment. The delivery of human erythropoietin (hEPO) cDNA
      to salivary glands reportedly increases red blood cell counts, haematocrit (HCT)
      and haemoglobin concentration, representing a potential new method of renal
      anaemia treatment. However, no studies have examined the effects of this method
      in an animal model of renal anaemia. Here we established a miniature pig animal
      model of renal anaemia through continuous feeding with adenine. In these animals,
      we delivered the AAV2hEPO gene to the parotid glands through Stensen's duct. As a
      control, we transferred AAVLacZ. Enzyme-linked immunosorbent assay was used to
      detect hEPO in serum and saliva. Red blood counts and serum biochemistry were
      used to evaluate how hEPO gene administration affected renal anaemia. Compared
      with the control group, we found increased hEPO concentrations in parotid saliva
      and serum, respectively, at 2 and 6 weeks after AAV2hEPO administration to the
      anaemic animals. HCT and haemoglobin were also increased after AAV2hEPO was
      delivered; most serum indicators of renal damage were not changed over the time
      span of the experiment, suggesting the adenine-induced kidney damage had not been
      completely reversed. However, blood urea nitrogen and B2 microglobulin levels
      showed small but significant improvement. Overall, our present findings suggest
      that adeno-associated virus 2 (AAV2)-mediated gene transduction of hEPO via the
      parotid gland is a promising potential alternative therapy for renal anaemia.

PMID- 28753202
TI  - Targeting the CXCR4/CXCL12 axis in treating epithelial ovarian cancer.
AB  - Ovarian carcinoma is the most crucial and difficult target for available
      therapeutic treatments among gynecological malignancies, and great efforts are
      required to find an effective solution. Molecular studies showed that the
      chemokine stromal cell-derived factor-1 (also known as CXCL12) and its receptor,
      CXCR4, are key determinants of tumor initiation, progression and metastasis in
      ovarian carcinomas. Hence, it is generally believed that blocking the
      CXCR4/CXCL12 pathway could serve as a potential therapy for patients with ovarian
      cancer. Herein, we investigated the role of the CXCR4/CXCL12 axis in regulating
      ovarian cancer progression. Using flow cytometry, a real-time PCR and western
      blot analyses, we showed that the chemokine receptor CXCR4 protein and mRNA were
      overexpressed in human epithelial ovarian cancer cell lines, and these were
      closely correlated with poor outcomes. Moreover, silencing CXCR4 by small hairpin
      RNA in HTB75 cells reduced cell proliferation, migration and invasion and
      significantly reduced RhoA and Rac-1/Cdc42 expressions, whereas overexpression of
      CXCR4 in SKOV3 cells significantly increased cell migration and markedly
      increased RhoA, Rac-1/Cdc42 levels. Silencing CXCR4 also led to decreased in
      vitro cytotoxicity of AMD3100, a specific antagonist of CXCR4, which exerts its
      effect upon CXCR4 expression. Remarkably, knockdown of CXCR4 in HTB75 cells led
      to a significantly decreased capability to form tumors in vivo, and the Ki67
      proliferation index of xenograft tumors showed a dramatic reduction. Our results
      revealed that the CXCR4/CXCL12 pathway represents a promising therapeutic target
      for epithelial ovarian carcinoma.

PMID- 28753203
TI  - Management of neuromuscular diseases and spinal muscular atrophy in Latin
      America.
AB  - Latin America (LA) has a population of ~645 million people distributed over 33
      countries with marked political, cultural and economic differences. In LA,
      patients with inherited neuromuscular diseases (NMDs) often do not have access to
      specialized medical centers and many of them go undiagnosed. General management
      and care of spinal muscular dystrophy (SMA) patients in the region varies due to
      heterogeneous health care. An active generation of young clinical neurologists is
      being trained for the specialized care of SMA and other neuromuscular (NM)
      patients, both in the private and public sectors. The Euro-Latin-American Summer
      School of Myology (EVELAM) as well as efforts of professionals at large public
      centers in the major cities of LA have a leading role in this development.
      Different regional academic-scientific organizations as well as the expanding
      number of telethon centers and the creation of parent organizations, mostly
      concerning SMA, all together are contributing to the increased quality of the
      management of NMD patients. Over the past years, academic and clinical research,
      as well as the establishment of qualified centers for the molecular testing of
      NMD are pushing forward the creation of patient registries and the development of
      specific clinical trials, with Argentina and Brazil having a major role in this
      field. Nevertheless, increased awareness and further training of specialized
      health professionals are necessary to reach patients that are currently lacking
      care throughout the region.

PMID- 28753204
TI  - ASK1 facilitates tumor metastasis through phosphorylation of an ADP receptor
      P2Y12 in platelets.
AB  - Tumor metastasis is the major cause of deaths in cancer patients and is modulated
      by intertwined stress-responsive signaling cascades. Here we demonstrate that
      deletion of stress-responsive apoptosis signal-regulating kinase 1 (Ask1) in
      platelets results in unstable hemostasis and drastic attenuation of tumor lung
      metastasis, both of which are attributable to platelet dysfunction. Platelet
      specific deletion of Ask1 in mice leads to defects in ADP-dependent platelet
      aggregation, unstable hemostasis and subsequent attenuation of tumor metastasis.
      We also revealed that activating phosphorylation of Akt is attenuated in Ask1
      deficient platelets, contrary to the previous reports suggesting that Akt is
      negatively regulated by ASK1. Mechanistically, ASK1-JNK/p38 axis phosphorylates
      an ADP receptor P2Y12 at Thr345, which is required for the ADP-dependent
      sustained Akt activity that is vital to normal platelet functions. Our findings
      offer insight into positive regulation of Akt signaling through P2Y12
      phosphorylation as well as MAPK signaling in platelets by ASK1 and suggest that
      ASK1-JNK/p38 axis provides a new therapeutic opportunity for tumor metastasis.

PMID- 28753205
TI  - An update on using CRISPR/Cas9 in the one-cell stage mouse embryo for generating
      complex mutant alleles.

PMID- 28753206
TI  - TRPM2-mediated rise in mitochondrial Zn2+ promotes palmitate-induced
      mitochondrial fission and pancreatic beta-cell death in rodents.
AB  - Rise in plasma free fatty acids (FFAs) represents a major risk factor for obesity
      induced type 2 diabetes. Saturated FFAs cause a progressive decline in insulin
      secretion by promoting pancreatic beta-cell death through increased production of
      reactive oxygen species (ROS). Recent studies have demonstrated that palmitate (a
      C16-FFA)-induced rise in ROS causes beta-cell death by triggering mitochondrial
      fragmentation, but the underlying mechanisms are unclear. Using the INS1-832/13
      beta-cell line, here we demonstrate that palmitate generates the ROS required for
      mitochondrial fission by activating NOX (NADPH oxidase)-2. More importantly, we
      show that chemical inhibition, RNAi-mediated silencing and knockout of ROS
      sensitive TRPM (transient receptor potential melastatin)-2 channels prevent
      palmitate-induced mitochondrial fission. Although TRPM2 activation affects the
      intracellular dynamics of Ca2+ and Zn2+, chelation of Zn2+ alone was sufficient
      to prevent mitochondrial fission. Consistent with the role of Zn2+, palmitate
      caused a rise in mitochondrial Zn2+, leading to Zn2+-dependent mitochondrial
      recruitment of Drp-1 (a protein that catalyses mitochondrial fission) and loss of
      mitochondrial membrane potential. In agreement with the previous reports, Ca2+
      caused Drp-1 recruitment, but it failed to induce mitochondrial fission in the
      absence of Zn2+. These results indicate a novel role for Zn2+ in mitochondrial
      dynamics. Inhibition or knockout of TRPM2 channels in mouse islets and RNAi
      mediated silencing of TRPM2 expression in human islets prevented FFA/cytokine
      induced beta-cell death, findings that are consistent with the role of abnormal
      mitochondrial fission in cell death. To conclude, our results reveal a novel,
      potentially druggable signalling pathway for FFA-induced beta-cell death. The
      cascade involves NOX-2-dependent production of ROS, activation of TRPM2 channels,
      rise in mitochondrial Zn2+, Drp-1 recruitment and abnormal mitochondrial fission.

PMID- 28753207
TI  - The proline rich domain of p53 is dispensable for MGMT-dependent DNA repair and
      cell survival following alkylation damage.
AB  - In addition to promoting cell death and senescence, p53 also has important
      cellular survival functions. A mutant p53, lacking a proline-rich domain
      (p53DeltaP), that is deficient in controlling both cell death and cell cycle
      arrest, was employed to determine the biological means by which p53 mediates
      survival upon DNA damage. While p53DeltaP and p53-/- cells were equally resistant
      to many DNA damaging agents, p53DeltaP cells showed an exquisite resistance to
      high doses of the alkylating agent Diazald (N-Methyl-N-(p
      tolylsulfonyl)nitrosamide), as compared to cells completely deficient for p53
      function. We determined that p53DeltaP was capable of transcribing the repair
      gene, MGMT (O6-methylguanine-DNA methyltransferase) after irradiation or
      alkylation damage, resulting in DNA repair and cell survival. Consistent with
      these observations, p53DeltaP mice show enhanced survival after IR relative to
      p53-/- mice. Suppression or deletion of MGMT expression in p53DeltaP cells
      inhibited DNA repair and survival after alkylation damage, whereas MGMT
      overexpression in p53-deficient cells facilitated DNA repair and conferred
      survival advantage. This study shows that when cell death and cell cycle arrest
      pathways are inhibited, p53 can still mediate MGMT-dependent repair, to promote
      cell survival upon DNA damage.

PMID- 28753208
TI  - Ice nucleation active bacteria in precipitation are genetically diverse and
      nucleate ice by employing different mechanisms.
AB  - A growing body of circumstantial evidence suggests that ice nucleation active
      (Ice+) bacteria contribute to the initiation of precipitation by heterologous
      freezing of super-cooled water in clouds. However, little is known about the
      concentration of Ice+ bacteria in precipitation, their genetic and phenotypic
      diversity, and their relationship to air mass trajectories and precipitation
      chemistry. In this study, 23 precipitation events were collected over 15 months
      in Virginia, USA. Air mass trajectories and water chemistry were determined and
      33 134 isolates were screened for ice nucleation activity (INA) at -8  degrees C.
      Of 1144 isolates that tested positive during initial screening, 593 had confirmed
      INA at -8  degrees C in repeated tests. Concentrations of Ice+ strains in
      precipitation were found to range from 0 to 13 219 colony forming units per
      liter, with a mean of 384+/-147. Most Ice+ bacteria were identified as members of
      known and unknown Ice+ species in the Pseudomonadaceae, Enterobacteriaceae and
      Xanthomonadaceae families, which nucleate ice employing the well-characterized
      membrane-bound INA protein. Two Ice+ strains, however, were identified as
      Lysinibacillus, a Gram-positive genus not previously known to include Ice+
      bacteria. INA of the Lysinibacillus strains is due to a nanometer-sized molecule
      that is heat resistant, lysozyme and proteinase resistant, and secreted. Ice+
      bacteria and the INA mechanisms they employ are thus more diverse than expected.
      We discuss to what extent the concentration of culturable Ice+ bacteria in
      precipitation and the identification of a new heat-resistant biological INA
      mechanism support a role for Ice+ bacteria in the initiation of precipitation.

PMID- 28753209
TI  - Drought and host selection influence bacterial community dynamics in the grass
      root microbiome.
AB  - Root endophytes have been shown to have important roles in determining host
      fitness under periods of drought stress, and yet the effect of drought on the
      broader root endosphere bacterial community remains largely uncharacterized. In
      this study, we present phylogenetic profiles of bacterial communities associated
      with drought-treated root and rhizosphere tissues of 18 species of plants with
      varying degrees of drought tolerance belonging to the Poaceae family, including
      important crop plants. Through 16S rRNA gene profiling across two distinct
      watering regimes and two developmental time points, we demonstrate that there is
      a strong correlation between host phylogenetic distance and the microbiome
      dissimilarity within root tissues, and that drought weakens this correlation by
      inducing conserved shifts in bacterial community composition. We identify a
      significant enrichment in a wide variety of Actinobacteria during drought within
      the roots of all hosts, and demonstrate that this enrichment is higher within the
      root than it is in the surrounding environments. Furthermore, we show that this
      observed enrichment is the result of an absolute increase in Actinobacterial
      abundance and that previously hypothesized mechanisms for observed enrichments in
      Actinobacteria in drought-treated soils are unlikely to fully account for the
      phenomena observed here within the plant root.

PMID- 28753211
TI  - Corrigendum: Stk38 Modulates Rbm24 Protein Stability to Regulate Sarcomere
      Assembly in Cardiomyocytes.
AB  - This corrects the article DOI: 10.1038/srep44870.

PMID- 28753210
TI  - Biogeography and organic matter removal shape long-term effects of timber
      harvesting on forest soil microbial communities.
AB  - The growing demand for renewable, carbon-neutral materials and energy is leading
      to intensified forest land-use. The long-term ecological challenges associated
      with maintaining soil fertility in managed forests are not yet known, in part due
      to the complexity of soil microbial communities and the heterogeneity of forest
      soils. This study determined the long-term effects of timber harvesting,
      accompanied by varied organic matter (OM) removal, on bacterial and fungal soil
      populations in 11- to 17-year-old reforested coniferous plantations at 18 sites
      across North America. Analysis of highly replicated 16 S rRNA gene and ITS region
      pyrotag libraries and shotgun metagenomes demonstrated consistent changes in
      microbial communities in harvested plots that included the expansion of
      desiccation- and heat-tolerant organisms and decline in diversity of
      ectomycorrhizal fungi. However, the majority of taxa, including the most abundant
      and cosmopolitan groups, were unaffected by harvesting. Shifts in microbial
      populations that corresponded to increased temperature and soil dryness were
      moderated by OM retention, which also selected for sub-populations of fungal
      decomposers. Biogeographical differences in the distribution of taxa as well as
      local edaphic and environmental conditions produced substantial variation in the
      effects of harvesting. This extensive molecular-based investigation of forest
      soil advances our understanding of forest disturbance and lays the foundation for
      monitoring long-term impacts of timber harvesting.

PMID- 28753212
TI  - AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse
      model of Leigh syndrome.
AB  - Leigh syndrome (LS) is the most common infantile mitochondrial encephalopathy. No
      treatment is currently available for this condition. Mice lacking Ndufs4,
      encoding NADH: ubiquinone oxidoreductase iron-sulfur protein 4 (NDUFS4)
      recapitulates the main findings of complex I (cI)-related LS, including severe
      multisystemic cI deficiency and progressive neurodegeneration. In order to
      develop a gene therapy approach for LS, we used here an AAV2/9 vector carrying
      the human NDUFS4 coding sequence (hNDUFS4). We administered AAV2/9-hNDUFS4 by
      intravenous (IV) and/or intracerebroventricular (ICV) routes to either newborn or
      young Ndufs4-/- mice. We found that IV administration alone was only able to
      correct the cI deficiency in peripheral organs, whereas ICV administration
      partially corrected the deficiency in the brain. However, both treatments failed
      to improve the clinical phenotype or to prolong the lifespan of Ndufs4-/- mice.
      In contrast, combined IV and ICV treatments resulted, along with increased cI
      activity, in the amelioration of the rotarod performance and in a significant
      prolongation of the lifespan. Our results indicate that extraneurological organs
      have an important role in LS pathogenesis and provide an insight into current
      limitations of adeno-associated virus (AAV)-mediated gene therapy in multisystem
      disorders. These findings warrant future investigations to develop new vectors
      able to efficiently target multiple organs.

PMID- 28753213
TI  - Comment on "Proton transport in barium stannate: classical, semi-classical and
      quantum regimes" by G. Geneste, A. Ottochian, J. Hermet and G. Dezanneau, Phys.
      Chem. Chem. Phys., 2015, 17, 19104.
AB  - In a recent paper in this journal, proton transport in oxides was considered in
      terms of density functional theory and the non-adiabatic Flynn-Stoneham approach
      of small polaron type proposed much earlier for metals. Also, regimes of hydrogen
      diffusion relevant to oxides were reviewed, but the straightforwardly observable
      channel of low-temperature over-barrier jumps has passed unnoticed. We offer this
      latter possibility, together with some additional arguments, to make our
      objection more compelling. There are two major contentious findings in the
      article. First, in discussing the phonon-assisted quantum regime and the
      adiabatic coincidence configuration in barium stannate, the article claimed that
      the models based on a fully non-adiabatic picture for metals cannot be
      generalized to proton-conducting oxides. It is difficult to agree with such a
      viewpoint because such generalizations are being published. By means of a
      counterexample, this comment illustrates the real efficacy of using Flynn
      Stoneham-like models in studying these oxides. Second, we have strong grounds for
      supposing that the main claim of the paper being commented on about the adiabatic
      nature of the proton transfer is in conflict with general interpretation of small
      polaron hopping. The exact knowledge of energy barriers for proton transfer is
      needed to confirm the validity of assuming an adiabatic regime. Since the most
      likely influence of the functional on the adiabaticity criterion formulation is
      certainly evident, comparison of the results of Geneste et al. to results
      obtained with higher functionals may check the validity of the present GGA-PBE
      scheme.

PMID- 28753214
TI  - Quantitative prediction of the position and orientation for an octahedral
      nanoparticle at liquid/liquid interfaces.
AB  - Shape-controlled polyhedral particles and their assembled structures have
      important applications in plasmonics and biosensing, but the interfacial
      configurations that will critically determine their resultant assembled
      structures are not well-understood. Hence, a reliable theory is desirable to
      predict the position and orientation of a polyhedron at the vicinity of a
      liquid/liquid interface. Here we demonstrate that the free energy change theory
      can quantitatively predict the position and orientation of an isolated octahedral
      nanoparticle at a liquid/liquid interface, whose vertices and facets can play
      crucial roles in biosensing. We focus on two limiting orientations of an
      octahedral nanoparticle, vertex up and facet up. Our proposed theory indicates
      that the surface wettability (hydrophilic/hydrophobic ratio) of the nanoparticle
      determines its most stable position and the preferred orientation at a water/oil
      interface. The surface wettability of an octahedron is adjusted from extremely
      hydrophobic to extremely hydrophilic by changing the amount of charge on the Ag
      surface in molecular dynamics (MD) simulations. The MD simulations results are in
      excellent agreement with our theoretical prediction for an Ag octahedral
      nanoparticle at a hexane/water interface. Our proposed theory bridges the gap
      between molecular-level simulations and equilibrium configurations of polyhedral
      nanoparticles in experiments, where insights from nanoparticle intrinsic
      wettability details can be used to predict macroscopic superlattice formation
      experimentally. This work advances our ability to precisely predict the final
      structures of the polyhedral nanoparticle assemblies at a liquid/liquid
      interface.

PMID- 28753215
TI  - Towards in situ determination of 3D strain and reorientation in the
      interpenetrating nanofibre networks of cuticle.
AB  - Determining the in situ 3D nano- and microscale strain and reorientation fields
      in hierarchical nanocomposite materials is technically very challenging. Such a
      determination is important to understand the mechanisms enabling their functional
      optimization. An example of functional specialization to high dynamic mechanical
      resistance is the crustacean stomatopod cuticle. Here we develop a new 3D X-ray
      nanostrain reconstruction method combining analytical modelling of the
      diffraction signal, fibre-composite theory and in situ deformation, to determine
      the hitherto unknown nano- and microscale deformation mechanisms in stomatopod
      tergite cuticle. Stomatopod cuticle at the nanoscale consists of mineralized
      chitin fibres and calcified protein matrix, which form (at the microscale)
      plywood (Bouligand) layers with interpenetrating pore-canal fibres. We uncover
      anisotropic deformation patterns inside Bouligand lamellae, accompanied by load
      induced fibre reorientation and pore-canal fibre compression. Lamination theory
      was used to decouple in-plane fibre reorientation from diffraction intensity
      changes induced by 3D lamellae tilting. Our method enables separation of
      deformation dynamics at multiple hierarchical levels, a critical consideration in
      the cooperative mechanics characteristic of biological and bioinspired materials.
      The nanostrain reconstruction technique is general, depending only on molecular
      level fibre symmetry and can be applied to the in situ dynamics of advanced
      nanostructured materials with 3D hierarchical design.

PMID- 28753216
TI  - Strabismus After Ocular Surgery.
AB  - Many types of ocular surgery can cause diplopia, including eyelid, conjunctival,
      cataract, refractive, glaucoma, retinal, and orbital surgery. Mechanisms include
      direct injury to the extraocular muscles from surgery or anesthesia, scarring of
      the muscle complex and/or conjunctiva, alteration of the muscle pulley system,
      mass effects from implants, and muscle displacement. Diplopia can also result
      from a loss of fusion secondary to long-standing poor vision in one eye or from a
      decompensation of preexisting strabismus that was not recognized preoperatively.
      Treatment, which typically begins with prisms and is followed by surgery when
      necessary, can be challenging. In this review, the incidence, mechanisms, and
      treatments involved in diplopia after various ocular surgeries are discussed. [J
      Pediatr Ophthalmol Strabismus. 2017;54(5):272-281.].

PMID- 28753217
TI  - Retrospective Study of Visual Outcomes and Complications After Sutureless,
      Flapless, and Glueless Intrascleral Fixation of Posterior Chamber Intraocular
      Lens in Children and Young Adults.
AB  - PURPOSE: To evaluate the visual outcomes and complications after sutureless,
      flapless, and glueless intrascleral fixation of a posterior chamber intraocular
      lens (IOL) in patients between the ages of 5 and 20 years. METHODS: Children with
      gross subluxated lenses and aphakia following intracapsular cataract extraction
      with inadequate posterior capsular support underwent intrascleral fixation of a
      standard three-piece posterior chamber IOL without sutures, flaps, or glue. A
      retrospective study of 15 eyes of 11 patients with a mean follow-up period of 6
      months was performed. The main outcome measures were improvement in visual acuity
      (best corrected [BCVA] and uncorrected [UCVA]) and early and late postoperative
      complications. RESULTS: Preoperative to postoperative mean UCVA changed from 1.34
      +/- 0.35 to 0.36 +/- 0.18 logarithm of the minimum angle of resolution (logMAR),
      respectively (P < .001). Preoperative to postoperative mean BCVA changed from
      0.69 +/- 0.37 to 0.19 +/- 0.19 logMAR, respectively (P < .001). Two patients
      showed early postoperative complications within 1 week. One patient presented
      with vitreous hemorrhage and the other with hyphema on postoperative day 1. Both
      patients were treated conservatively and recovered by the first follow-up visit.
      None of the patients showed late postoperative complications during the 6-month
      follow-up period. The final visual outcome between the complication (n = 2) and
      no complication (n = 13) groups showed no statistically significant difference (P
      = .91). The final visual outcome between the eyes with primary and secondary
      implantation was similar with no statistically significant difference (P = .857).
      CONCLUSIONS: The technique of flapless, glueless, and sutureless scleral fixation
      of a three-piece IOL has shown significant improvement in visual acuity and does
      not cause significant complications postoperatively. [J Pediatr Ophthalmol
      Strabismus. 2017;54(6):381-386.].

PMID- 28753218
TI  - A review of late complications of allogeneic hematopoietic stem cell
      transplantations.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective
      and curative treatment of different malignant and non-malignant diseases. Early
      transplant-related mortality after allo-HSCT has decreased with reduced-intensity
      conditioning regimens and effective anti-infectious treatments, but late
      transplant-related mortality is still a problem. Physicians are now paying more
      attention to late complications that may worsen the quality of life of many
      transplant recipients. Chronic graft versus host disease (cGVHD) is one of the
      major causes of late transplant-related mortality after allo-HSCT. This review
      discusses recent advances that have been made in clinical evaluation and
      treatment of late transplant-related complications including cGVHD. The different
      sites of involvement are organs, especially the skin and eye, and the
      gastrointestinal, endocrinologic, metabolic, renal, cardiologic, pulmonary,
      connective tissue, and neurological systems. In addition, this review includes
      infections and secondary malignancies in post-transplant settings that worsen
      quality of life in long-term follow-ups.

PMID- 28753219
TI  - The retrograde transverse cervical artery as a recipient vessel for free tissue
      transfer in complex head and neck reconstruction with a vessel-depleted neck.
AB  - BACKGROUND: Reconstruction in a vessel-depleted neck is challenging. The success
      rates can be markedly decreased because of unavailability of suitable recipient
      vessels. In order to obtain a reliable flow, recipient vessels away from the zone
      of fibrosis, radiation, or infection need to be explored. The aim of this report
      is to present our experience and clinical outcomes using the retrograde flow
      coming from the distal transverse cervical artery (TCA) as a source for arterial
      inflow for complex head and neck reconstruction in patients with a vessel
      depleted neck. METHODS: Between July 2010 and June 2016, nine patients with a
      vessel-depleted neck underwent secondary head and neck reconstruction using the
      retrograde TCA as recipient vessel for microanastomosis. The mean age was 49.6
      years (range, 36 to 68 years). All patients had previous bilateral neck
      dissections and all, except one, had also received radiotherapy. Indications
      included neck contracture release (n = 3), oral (n = 1), mandibular (n = 3) and
      pharyngoesophageal (n = 2) reconstruction necessitating free anterolateral thigh
      (n = 3) and medial sural artery (n = 1) perforator flaps, fibula (n = 3) and
      ileocolon (n = 2) flaps respectively. RESULTS: There was 100% flap survival rate
      with no re-exploration or any partial flap loss. One case of intra-operative
      arterial vasospasm at the anastomotic suture line was managed intra-operatively
      with vein graft interposition. There were no other complications or donor site
      morbidity during the follow-up period. CONCLUSIONS: In a vessel-depleted neck,
      the reverse flow of the TCA may be a reliable option for complex secondary head
      and neck reconstruction in selected patients.

PMID- 28753220
TI  - A novel method for rapid and quantitative mechanical assessment of soft tissue
      for diagnostic purposes: A computational study.
AB  - Biological tissues often experience drastic changes in their microstructure due
      to their pathophysiological conditions. Such microstructural changes could result
      in variations in mechanical properties, which can be used in diagnosing or
      monitoring a wide range of diseases, most notably cancer. This paves the avenue
      for non-invasive diagnosis by instrumented palpation although challenges remain
      in quantitatively assessing the amount of diseased tissue by means of mechanical
      characterization. This paper presents a framework for tissue diagnosis using a
      quantitative and efficient estimation of the fractions of cancerous and non
      cancerous tissue without a priori knowledge of tissue microstructure. First, the
      sample is tested in a creep or stress relaxation experiment, and the behavior is
      characterized using a single term Prony series. A rule of mixtures, which relates
      tumor fraction to the apparent mechanical properties, is then obtained by
      minimizing the difference between strain energy of a heterogeneous system and an
      equivalent homogeneous one. Finally, the percentage of each tissue constituent is
      predicted by comparing the observed relaxation time with that calculated from the
      rule of mixtures. The proposed methodology is assessed using models reconstructed
      from histological samples and magnetic resonance imaging of prostate. Results
      show that estimation of cancerous tissue fraction can be obtained with a maximum
      error of 12% when samples of different sizes, geometries, and tumor fractions are
      presented. The proposed framework has the potential to be applied to a wide range
      of diseases such as rectal polyps, cirrhosis, or breast and prostate cancer whose
      current primary diagnosis remains qualitative.

PMID- 28753221
TI  - Beneficial or deleterious effects of vascular endothelial growth factor may
      depend on the isoform involved.

PMID- 28753222
TI  - Acute hemorrhagic rectal ulcer syndrome: Comparison with non-hemorrhagic rectal
      ulcer lower gastrointestinal bleeding.
AB  - OBJECTIVE: The aim of this study was to describe the clinical characteristics of
      acute hemorrhagic rectal ulcer (AHRU) and to elucidate its predictive factors.
      METHODS: The medical records of patients with AHRU were retrospectively reviewed.
      Their baseline clinical characteristics were compared with those of patients with
      non-AHRU lower gastrointestinal bleeding to identify predictive factors for AHRU.
      RESULTS: Among the 118 patients who underwent emergency endoscopy due to acute
      massive hematochezia from 2013 to 2015, 25 (21.2%) were diagnosed as having AHRU.
      Of them, 22 (88.0%) were successfully managed endoscopically and 3 (12.0%)
      underwent surgery. Six (24.0%) patients developed rebleeding within 1-9 days
      after the initial bleeding, which was controlled by a repeat endoscopy. Five
      (20.0%) died during follow-up. A multivariate-adjusted logistic regression
      analysis revealed that a lower serum albumin level, worse Eastern Cooperative
      Oncology Group (ECOG) performance status and history of constipation were
      significant factors for predicting AHRU. Hypoalbuminemia (<30 g/L) had a
      sensitivity, specificity and positive and negative predictive values of 84.0%,
      78.5%, 51.2% and 94.8% for predicting AHRU, respectively. CONCLUSIONS:
      Approximately 20% of patients with massive hematochezia had AHRU. Most patients
      with AHRU can be managed endoscopically. Low serum albumin level, poor ECOG
      performance status and prior constipation could be used in distinguishing
      patients with and without AHRU, facilitating the selection of optimal bowel
      preparation method for massive hematochezia.

PMID- 28753223
TI  - Biphasic influence of Staphylococcus aureus on human epidermal tight junctions.
AB  - Bacterial infections (e.g., with Staphylococcus aureus) are serious problems in
      skin with a compromised barrier, such as in patients with atopic dermatitis.
      Previously, it was shown that tight junction (TJ) proteins are influenced by
      staphylococcal infection, and TJ function is impaired after infection of the
      keratinocyte cell line HaCaT. However, functional studies in cells or models more
      similar to human skin are missing. Therefore, we investigated bacterial
      colonialization and infection with live S. aureus in primary human keratinocytes
      and reconstructed human epidermis (RHE). We show that short-term inoculation
      results in increased TJ barrier function-which could not be seen in HaCaT cells
      hinting at an early protective effect. This is accompanied by occludin
      phosphorylation and sustained localization of occludin and claudin-4 at cell
      membranes. Long-term incubation resulted in decreased presence of claudin-1 and
      claudin-4 at cell membranes and decreased TJ barrier function. The agr regulon of
      S. aureus plays a role in the increasing but not in the decreasing effect.
      Proinflammatory cytokines, which are produced as a result of S. aureus
      inoculation, influence both phases. In summary, we show here that S. aureus can
      have short-term promoting effects on the TJ barrier, while in the long term it
      results in disturbance of TJs.

PMID- 28753224
TI  - Aspergillus fumigatus protein phosphatase PpzA is involved in iron assimilation,
      secondary metabolite production, and virulence.
AB  - Metal restriction imposed by mammalian hosts during an infection is a common
      mechanism of defence to reduce or avoid the pathogen infection. Metals are
      essential for organism survival due to its involvement in several biological
      processes. Aspergillus fumigatus causes invasive aspergillosis, a disease that
      typically manifests in immunocompromised patients. A. fumigatus PpzA, the
      catalytic subunit of protein phosphatase Z (PPZ), has been recently identified as
      associated with iron assimilation. A. fumigatus has 2 high-affinity mechanisms of
      iron acquisition during infection: reductive iron assimilation and siderophore
      mediated iron uptake. It has been shown that siderophore production is important
      for A. fumigatus virulence, differently to the reductive iron uptake system.
      Transcriptomic and proteomic comparisons between ?ppzA and wild-type strains
      under iron starvation showed that PpzA has a broad influence on genes involved in
      secondary metabolism. Liquid chromatography-mass spectrometry under standard and
      iron starvation conditions confirmed that the DeltappzA mutant had reduced
      production of pyripyropene A, fumagillin, fumiquinazoline A, triacetyl-fusarinine
      C, and helvolic acid. The DeltappzA was shown to be avirulent in a neutropenic
      murine model of invasive pulmonary aspergillosis. PpzA plays an important role at
      the interface between iron starvation, regulation of SM production, and
      pathogenicity in A. fumigatus.

PMID- 28753225
TI  - Review of dynamic contrast-enhanced MRI: Technical aspects and applications in
      the musculoskeletal system.
AB  - : Although postcontrast imaging has been used for many years in musculoskeletal
      imaging, dynamic contrast enhanced (DCE) MRI is not routinely used in many
      centers around the world. Unlike conventional contrast-enhanced sequences, DCE
      MRI allows the evaluation of the temporal pattern of enhancement in the
      musculoskeletal system, perhaps best known for its use in oncologic applications
      (such as differentiating benign from malignant tumors, evaluating for treatment
      response after neoadjuvant chemotherapy, and differentiating postsurgical changes
      from residual tumor). However, DCE-MRI can also be used to evaluate inflammatory
      processes such as Charcot foot and synovitis, and evaluate bone perfusion in
      entities like Legg Calve Perthes disease and arthritis. Finally, vascular
      abnormalities and associated complications may be better characterized with DCE
      MRI than conventional imaging. The goal of this article is to review the
      applications and technical aspects of DCE-MRI in the musculoskeletal system.
      LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging
      2018;47:875-890.

PMID- 28753226
TI  - Golgi alpha1,4-fucosyltransferase of Arabidopsis thaliana partially localizes at
      the nuclear envelope.
AB  - We analyzed plant-derived alpha1,4-fucosyltransferase (FucTc) homologs by
      reporter fusions and focused on representatives of the Brassicaceae and
      Solanaceae. Arabidopsis thaliana AtFucTc-green fluorescent protein (GFP) or
      tomato LeFucTc-GFP restored Lewis-a formation in a fuctc mutant, confirming
      functionality in the trans-Golgi. AtFucTc-GFP partly accumulated at the nuclear
      envelope (NE) not observed for other homologs or truncated AtFucTc lacking the N
      terminus or catalytic domain. Analysis of At/LeFucTc-GFP swap constructs with
      exchanged cytosolic, transmembrane and stalk (CTS), or only the CT regions,
      revealed that sorting information resides in the membrane anchor. Other domains
      of AtFuctc also contribute, since amino-acid changes in the CT region strongly
      reduced but did not abolish NE localization. By contrast, two N-terminal GFP
      copies did, indicating localization at the inner nuclear membrane (INM).
      Tunicamycin treatment of AtFucTc-GFP abolished NE localization and enhanced
      overlap with an endosomal marker, suggesting involvement of N-glycosylation. Yet
      neither expression in protoplasts of Arabidopsis N-glycosylation mutants nor
      elimination of the N-glycosylation site in AtFucTc prevented perinuclear
      accumulation. Disruption of endoplasmic reticulum (ER)-to-Golgi transport by co
      expression of Sar1(H74L) trapped tunicamycin-released AtFucTc-GFP in the ER,
      however, without NE localization. Since recovery after tunicamycin-washout
      required de novo-protein synthesis, our analyses suggest that AtFucTc localizes
      to the NE/INM due to interaction with an unknown (glyco)protein.

PMID- 28753227
TI  - Determinants of influenza vaccination in older adults: A nationwide community
      based study in Taiwan.
AB  - AIMS: Influenza vaccination (InVa) is an effective measure for preventing
      influenza infection, which is a major cause of morbidity and mortality in older
      adults. However, the determinants of InVa remain unclear. METHODS: The present
      study included 4756 adults aged 55 years and older who completed the baseline
      examination of the Healthy Aging Longitudinal Study in Taiwan. During the
      examination, each participant received assessments of InVa status. Comprehensive
      assessments of sociodemographic (age, sex, education level, marital status,
      living alone and occupation) and health-related factors (chronic diseases,
      smoking status, alcohol intake, physical activities, cognitive status and
      physical performance) were also carried out. The InVa rate was defined as the
      number of participants who reported receiving free InVa divided by the total
      number of candidates for free InVa. Multinomial logistic regression analysis was
      applied to investigate the sociodemographic and health-related determinants of
      InVa status. RESULTS: The coverage rate of InVa was 44.8% (2130/4756). Older age
      (adjusted odds ratio [OR; >75 years vs <65 years] 7.72, 95% CI 6.26-9.52),
      multiple chronic diseases (OR [>=2 vs 0)] 1.31, 95% CI 1.10-1.65) and physical
      activity (OR [yes vs no] 1.43, 95% CI 1.23-1.64) were positively associated with
      receiving InVa. A current smoking status (OR 0.67, 95% CI 0.55-0.82) was
      negatively associated with receiving InVa. CONCLUSIONS: Older adults who received
      InVa differed from non-receivers in multiple sociodemographic and health-related
      characteristics. These findings support continual efforts to improve the InVa
      coverage rate in vulnerable populations. Geriatr Gerontol Int 2017; 17: 2396
      2402.

PMID- 28753228
TI  - USE of arterialized saphenous vein venous flow-through flaps as a temporizing
      measure for hand salvage in contaminated wounds presenting with limb ischemia: A
      case series.
AB  - BACKGROUND: Vascular injuries resulting in limb ischemia are traditionally
      treated acutely with autologous or prosthetic bypass grafts. Traumatic
      contaminated injuries with soft tissue and vascular segmental loss are
      challenging as prosthetic bypasses are at risk of erosion, infection, and
      occlusion; and autologous bypasses are at risk of desiccation, blow-out,
      infection, and clotting. We propose a novel approach to these injuries by using
      arterialized saphenous vein venous flow-through free flaps (S-VFTF) as an
      autologous bypass, and present the results of its application in a series of
      cases. METHODS: Spanning 2008 to 2015, four patients presenting with large
      contaminated crush/avulsion wounds with vascular injury underwent hand
      revascularization with S-VFTF, allowing the contaminated wounds to be serially
      debrided. Definitive soft tissue reconstruction was performed once the wound was
      considered clean. The S-VFTF skin paddle was de-epithelialized and the soft
      tissue defect covered with a free latissimus dorsi flap or a rectus abdominis
      myocutaneous flap. RESULTS: All ischemic limbs were successfully reperfused and
      there were no take backs for perfusion issues. All S-VFTF remained patent at
      discharge and final follow-up. No partial or complete finger/hand amputations
      were required. All definitive coverage free flap survived with no complications.
      CONCLUSION: The two-stage reconstruction presented may help reconstructive and
      vascular surgeons consider alternatives to traditional vascular reconstruction
      methods. This technique avoids an exposed vascular graft in an extensively
      contaminated open wound. It allows the surgeon to perform thorough and sufficient
      debridement of the wound, preventing definitive reconstruction in a not yet
      declared zone of injury.

PMID- 28753229
TI  - Rapid decline in insulin antibodies and glutamic acid decarboxylase
      autoantibodies with ibrutinib therapy of chronic lymphocytic leukaemia.
AB  - WHAT IS KNOWN AND OBJECTIVE: Ibrutinib is inhibiting the Bruton's tyrosine kinase
      (BTK), thereby influencing B-cell development. We describe an unexpected side
      effect of ibrutinib in two patients with chronic lymphocytic leukaemia concerning
      the vigorous decrease of two different diabetes-associated antibodies. CASE
      DESCRIPTION: Two weeks after onset of ibrutinib therapy, patient A frequently
      noticed symptoms of hypoglycaemia such as dizziness and blurred vision. Blood
      glucose declined to 35-40 mg/dL. He had to lower his insulin dose step by step.
      High levels of insulin antibodies which had developed during insulin therapy were
      detected. Seven weeks after start of ibrutinib, his insulin antibodies level had
      dropped by 54.6%. Patient B had a 54.1% decrease in his glutamic acid
      decarboxylase autoantibodies level after 7 weeks. WHAT IS NEW AND CONCLUSION: The
      inhibitory effect of ibrutinib on the levels of insulin antibodies and glutamic
      acid decarboxylase autoantibodies is a novel finding and may have implications
      for diabetes care.

PMID- 28753230
TI  - A centralized mailed program with stepped increases of support increases time in
      compliance with colorectal cancer screening guidelines over 5 years: A randomized
      trial.
AB  - BACKGROUND: Screening over many years is required to optimize reductions in
      colorectal cancer (CRC) mortality. However, no prior trials have compared
      strategies for obtaining long-term adherence. METHODS: Systems of Support to
      Increase Colorectal Cancer Screening and Follow-Up was implemented in an
      integrated health care organization in Washington State. Between 2008 and 2009,
      4675 individuals aged 50 to 74 years were randomized to receive the usual care
      (UC), which included clinic-based strategies to increase CRC screening (arm 1),
      or, in years 1 and 2, mailings with a call-in number for colonoscopy and mailed
      fecal tests (arm 2), mailings plus brief telephone assistance (arm 3), or
      mailings and assistance plus nurse navigation (arm 4). Active-intervention
      subjects (those in arms 2, 3, and 4 combined) who were still eligible for CRC
      screening were randomized to mailings being stopped or continued in years 3 and
      5. The time in compliance with CRC screening over 5 years was compared for
      persons assigned to any intervention and persons assigned to UC. Screening tests
      contributed time on the basis of national guidelines for screening intervals
      (fecal tests annually, sigmoidoscopy every 5 years, and colonoscopy every 10
      years). RESULTS: All participants contributed data, but they were censored at
      disenrollment, death, the age of 76 years, or a diagnosis of CRC. Compared with
      UC participants, intervention participants had 31% more adjusted covered time
      over 5 years (incidence rate ratio, 1.31; 95% confidence interval, 1.25-1.37;
      covered time, 47.5% vs 62.1%). Fecal testing accounted for almost all additional
      covered time. CONCLUSIONS: In a health care organization with clinic-based
      activities to increase CRC screening, a centralized program led to increased CRC
      screening adherence over 5 years. Longer term data on screening adherence and its
      impact on CRC outcomes are needed. Cancer 2017;123:4472-80. (c) 2017 American
      Cancer Society.

PMID- 28753231
TI  - PD-1 inhibitor-associated lichenoid inflammation with incidental suprabasilar
      acantholysis or vesiculation-Report of 4 cases.
AB  - BACKGROUND: Immune checkpoint agents targeting programmed cell death-1 protein
      (PD1) or cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) receptors are
      increasingly utilized in treatment of advanced malignancies. However, these
      immunotherapies are commonly associated with idiosyncratic cutaneous adverse
      reactions. Thus, recognition and awareness of these reactions are necessary.
      METHODS: We reviewed the skin biopsies of all patients on anti-PD1 therapy with
      or without ipilimumab who developed lichenoid inflammation and included those
      with microscopic suprabasal or intraepidermal clefts. RESULTS: Four patients
      presented with interface dermatitis with microscopic intraepidermal clefts. In 2
      patients, the clefts were well developed and had some acantholytic cells while
      the other 2 appeared to be spongiosis or inflammation related. Immunofluorescence
      was negative in 1 patient. None of them had clinical findings in keeping with
      paraneoplastic pemphigus (PP) and the symptoms improved with either topical
      corticosteroid or withdrawal of immunotherapy. CONCLUSIONS: Lichenoid drug
      reaction occurring in patients receiving anti-PD1 therapy may be associated with
      microscopic suprabasal or intraepidermal clefting. The clinical course was
      similar to lichenoid drug reactions without clefting even though some lesions may
      resemble PP microscopically.

PMID- 28753232
TI  - Salvianolic Acid B Inhibits High-Fat Diet-Induced Inflammation by Activating the
      Nrf2 Pathway.
AB  - Salvianolic acid B (Sal B) is a major water-soluble bioactive component of Salvia
      miltiorrhiza, which is a traditional Chinese medicine. We investigated the ways
      in which Sal B affects high-fat diet (HFD)-induced immunological function
      disorder remission using a C57BL/6 mouse model. We gave groups of C57BL/6 mice a
      normal diet (Control), a normal diet supplemented with Sal B (Control + Sal B), a
      high-fat diet (HF), and a high-fat diet supplemented with Sal B (HF + Sal B) for
      10 wk. Sal B supplementation decreased the body weight and plasma lipids,
      increased the fecal excretion of lipids, prevented the accumulation of chronic
      oxidative stress, and reversed the disproportionality of CD3+ CD4+ and CD3+ CD8+
      T lymphocytes compared to HFD. We found an increase in IL-6 and TNF-alpha, while
      IL-10 decreased in plasma after the HFD and Sal B reversed the deregulation of
      the Thl/Th2 ratio. In addition, HFD-induced inflammation was stopped by Sal B
      through the downregulation of nuclear factor-kappaB (NF-kappaB), cyclooxygenase-2
      (COX-2), and inducible NO synthesis (iNOS), and the upregulation of nuclear
      factor-erythroid 2-related factor 2 (Nrf2)-regulated genes. These findings
      demonstrated that Sal B could effectively attenuate inflammation by activating
      the Nrf2-mediated antioxidant defense system.

PMID- 28753233
TI  - Knockout of a P-glycoprotein gene increases susceptibility to abamectin and
      emamectin benzoate in Spodoptera exigua.
AB  - P-glycoprotein [P-gp or the ATP-binding cassette transporter B1 (ABCB1)] is an
      important participant in multidrug resistance of cancer cells, yet the precise
      function of this arthropod transporter is unknown. The aim of this study was to
      determine the importance of P-gp for susceptibility to insecticides in the beet
      armyworm (Spodoptera exigua) using clustered regularly interspaced short
      palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) gene-editing technology. We
      cloned an open reading frame (ORF) encoding the S. exigua P-gp protein (SeP-gp)
      predicted to display structural characteristics common to P-gp and other insect
      ABCB1 transporters. A knockout line with a frame shift deletion of four
      nucleotides in the SeP-gp ORF was established using the CRISPR/Cas9 gene-editing
      system to test its potential role in determining susceptibility to chemical
      insecticides or insecticidal proteins from the bacterium Bacillus thuringiensis
      (Bt). Results from comparative bioassays demonstrate that knockout of SeP-gp
      significantly increases susceptibility of S. exigua by around threefold to
      abamectin and emamectin benzoate (EB), but not to spinosad, chlorfenapyr, beta
      cypermethrin, carbosulfan indoxacarb, chlorpyrifos, phoxim, diafenthiuron,
      chlorfluazuron, chlorantraniliprole or two Bt toxins (Cry1Ca and Cry1Fa). Our
      data support an important role for SeP-gp in susceptibility of S. exigua to
      abamectin and EB and imply that overexpression of SeP-gp may contribute to
      abamectin and EB resistance in S. exigua.

PMID- 28753234
TI  - Manipulative interventions for reducing pulled elbow in young children.
AB  - BACKGROUND: Pulled elbow (nursemaid's elbow) is a common injury in young
      children. It often results from a sudden pull on the arm, usually by an adult or
      taller person, which pulls the radius through the annular ligament, resulting in
      subluxation (partial dislocation) of the radial head. It can also be caused by a
      fall or twist. The child experiences sudden acute pain and loss of function in
      the affected arm. Pulled elbow is usually treated by manual reduction of the
      subluxed radial head. Various manoeuvres can be applied; most commonly,
      supination of the forearm, often combined with flexion, and (hyper-)pronation. It
      is unclear which is most successful. This is an update of a Cochrane review first
      published in 2009 and last updated in 2011. OBJECTIVES: To compare the effects
      (benefits and harms) of the different methods used to manipulate pulled elbow in
      young children. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle
      Trauma Group Specialised Register, the Cochrane Central Register of Controlled
      Trials, MEDLINE, Embase, CINAHL, LILACS, PEDro, clinical trial registers and
      reference lists of articles. Date of last search: September 2016. SELECTION
      CRITERIA: Randomised or quasi-randomised controlled clinical trials evaluating
      manipulative interventions for pulled elbow were included. Our primary outcome
      was failure at the first attempt, necessitating further treatment. DATA
      COLLECTION AND ANALYSIS: Two review authors independently evaluated trials for
      inclusion, assessed risk of bias, and extracted data. We pooled data using a
      fixed-effect model. MAIN RESULTS: Overall, nine trials with 906 children (all
      younger than seven years old and 58% of whom were female) were included, of which
      five trials were newly identified in this update. Eight trials were performed in
      emergency departments or ambulatory care centres, and one was performed in a
      tertiary paediatric orthopaedic unit. Four trials were conducted in the USA,
      three in Turkey, one in Iran, and one in Spain. Five trials were at high risk of
      selection bias because allocation was not concealed and all trials were at high
      risk of detection bias due to the lack of assessor blinding. Eight trials
      compared hyperpronation with supination-flexion. We found low-quality evidence
      that hyperpronation resulted in less failure at first attempt than supination
      flexion (9.2% versus 26.4%, risk ratio (RR) 0.35; 95% confidence interval (CI)
      0.25 to 0.50; 811 participants, 8 studies). Based on an illustrative risk of 268
      failures at first attempt per 1000 children treated using supination-flexion,
      this amounted to 174 fewer failures per 1000 children treated using
      hyperpronation (95% CI 134 to 201 fewer). Based on risk differences data, we also
      estimated a number needed to treat of 6 (95% CI 5 to 8); this means that six
      children would need to be treated with the hyperpronation method rather than the
      supination-flexion method to avoid one additional failure at the first
      attempt.The very low-quality evidence (from four studies) for pain during or
      after manipulation means that it is uncertain whether there is or is not a
      difference between pronation and supination-flexion. There was very low-quality
      evidence from six studies that repeat pronation may be more effective than repeat
      supination-flexion for the second attempt after initial failure. The remaining
      outcomes were either not reported (adverse effects, recurrence) or unsuitable for
      pooling (ultimate failure). Ultimate failure, reported for the overall population
      only because of the differences in the study protocols with respect to what to do
      after the first attempt failed, ranged from no ultimate failures in two studies
      to six failures (4.1% of 148 episodes) in one study.One trial compared supination
      extension versus supination-flexion. It provided very low-quality evidence
      (downgraded three levels for very serious risk of bias and serious imprecision)
      of no clear difference in failure at first attempt between the two methods.
      AUTHORS' CONCLUSIONS: There was low-quality evidence from eight small trials that
      the pronation method may be more effective at first attempt than the supination
      method for manipulating pulled elbow in young children. For other outcomes, no
      conclusions could be drawn either because of very low-quality evidence or the
      outcomes not being reported. We suggest that a high-quality randomised clinical
      trial comparing hyperpronation and supination-flexion is required to provide
      definitive evidence. We recommend that this is preceded by a survey among
      clinicians to establish the extent of clinical equipoise and to optimise the
      study design and recruitment.

PMID- 28753235
TI  - Study on the organization of cellular elements in the granulomatous lesion caused
      by chromoblastomycosis.
AB  - BACKGROUND: Chromoblastomycosis is a deep fungal infection characterized by a
      complex cellular granuloma. The aim of this study was to analyze the arrangement
      of cells responsible for the granuloma configuration of this disease by
      semiquantification of the cellular components of chromoblastomycosis skin
      biopsies. METHODS: The cells of cutaneous biopsies slides from 100 patients with
      untreated chromoblastomycosis were stained with hematoxylin-eosin and the
      granuloma cells were evaluated by microscopic examination of the elements of each
      granuloma and semiquantified the number of cells through its expressivity in
      crosses and the histopathological variables. Their presence were coded in degrees
      of intensity and classified in two categories: low expression and high
      expression. The cells that constituted the granulomas were separated into three
      groups: A, B and C. RESULTS: The chromoblastomycotic granuloma analyzed by this
      semiquantification of its cellular components showed that there was high
      expression of the elements setting up a mixed organized mycotic granuloma. It was
      observed that mononuclear phagocytic system (A), polymorphonuclear phagocytic
      system (B) and lymphoplasmocytic infiltrate (C) were located around the fungus.
      CONCLUSION: The results indicated that the granuloma present in the cutaneous
      lesion of chromoblastomycosis is a mixed organized mycotic granuloma with high
      expression of the cellular components.

PMID- 28753236
TI  - Blood-spinal cord barrier breakdown and pericyte deficiency in peripheral
      neuropathy.
AB  - The blood-spinal cord barrier (BSCB) prevents leakage of molecules, such as
      pronociceptive mediators, into the spinal cord, but its role in the
      pathophysiology of neuropathic pain is not completely understood. Rats with
      chronic constriction injury (CCI) develop mechanical allodynia, thermal
      hypersensitivity, and reduced motor performance (Rota-Rod test) compared with
      sham-injured mice-similar to mice with spared nerve injury (SNI). The BSCB
      becomes permeable for small and large tracers 1 day after nerve ligation.
      Messenger RNA (mRNA) expression of tight junction proteins (TJPs) occludin,
      claudin-1, claudin-5, claudin-19, tricellulin, and ZO-1 significantly declines 7
      14 days after CCI or SNI. ZO-1 and occludin are reduced in the cell membrane. In
      capillaries isolated from the spinal cord, immunoreactivity of claudin-5 and ZO-1
      is fainter. In parallel, the number of platelet-derived growth factor receptor
      beta (PDGF-beta)+ and CD13+ pericytes in the spinal cord drops. Reduced levels of
      cytosolic transcription factors like beta-catenin, but not SMAD4 and SLUG, could
      account for reduced TJP mRNA. In summary, neuropathy-induced
      allodynia/hypersensitivity is accompanied by a loss of pericytes in the spinal
      cord and a leaky BSCB. A better understanding of these pathways and mechanisms in
      neuropathic pain might foster the design of novel treatments to maintain spinal
      cord homeostasis.

PMID- 28753237
TI  - Genetic and epigenetic insight into morphospecies in a reef coral.
AB  - Incongruence between conventional and molecular systematics has left the
      delineation of many species unresolved. Reef-building corals are no exception,
      with phenotypic plasticity among the most plausible explanations for alternative
      morphospecies. As potential molecular signatures of phenotypic plasticity,
      epigenetic processes may contribute to our understanding of morphospecies. We
      compared genetic and epigenetic variation in Caribbean branching Porites spp.,
      testing the hypothesis that epigenetics-specifically, differential patterns of
      DNA methylation-play a role in alternative morphotypes of a group whose taxonomic
      status has been questioned. We used reduced representation genome sequencing to
      analyse over 1,000 single nucleotide polymorphisms and CpG sites in 27 samples of
      Porites spp. exhibiting a range of morphotypes from a variety of habitats in
      Belize. We found stronger evidence for genetic rather than epigenetic
      structuring, identifying three well-defined genetic groups. One of these groups
      exhibited significantly thicker branches, and branch thickness was a better
      predictor of genetic groups than depth, habitat or symbiont type. In contrast, no
      clear epigenetic patterns emerged with respect to phenotypic or habitat
      variables. While there was a weak positive correlation between pairwise genetic
      and epigenetic distance, two pairs of putative clones exhibited substantial
      epigenetic differences, suggesting a strong environmental effect. We speculate
      that epigenetic patterns are a complex mosaic reflecting diverse environmental
      histories superimposed over a relatively small heritable component. Given the
      role of genetics in branching Porites spp. morphospecies we were able to detect
      with genomewide sequencing, use of such techniques throughout the geographic
      range of these corals may help settle their phylogeny.

PMID- 28753238
TI  - Targeted Delivery of a Mannose-Conjugated BODIPY Photosensitizer by Nanomicelles
      for Photodynamic Breast Cancer Therapy.
AB  - The targeted delivery of a photosensitizer (PS) with appropriate carriers
      represents an attractive means of selectively delivering cargo to target tissues
      or subcellular compartments for photodynamic therapy (PDT). Herein, a three-arm
      distyryl BODIPY derivative conjugated with mannose units (denoted by BTM) that
      can co-assemble with Tween 80 to form nanomicelles (BTM-NMs) for targeted PDT is
      reported. MDA-MB-231 breast cancer cells recognized and specifically internalized
      BTM-NMs via mannose-receptor-mediated endocytosis with preferential accumulation
      in the lysosomes. These NMs could disassemble in cell lysosomes and subsequently
      induce highly efficient singlet oxygen (1 O2 ) generation upon light irradiation.
      1 O2 disrupted the lysosomal membrane and promoted the escape of BTM from the
      lysosome into the cytoplasm, thereby resulting in the efficient and selective
      killing of cancer cells through PDT. This study may provide a new strategy for
      designing targeted PDT systems to fight cancer.

PMID- 28753239
TI  - Family relations, sense of coherence, happiness and perceived health in retired
      Taiwanese: Analysis of a conceptual model.
AB  - AIM: A growing awareness of the rapidly increasing aged population in the world
      has led to growing attention to mental health in late life. Happiness has been
      emphasized as an important indicator of physical health and is predicted by a
      sense of coherence. However, the mechanism of influence of family relations on
      sense of coherence, happiness and perceived health is unknown. The present study
      aimed to analyze a conceptual model of the relationships among family relations,
      sense of coherence, happiness and perceived health in retired persons. METHODS: A
      total of 142 retired participants were recruited from social service centers in
      Taipei, Taiwan. A structured questionnaire measuring the relationships among
      family relations, sense of coherence, happiness and perceived health was filled
      in by each respondent. Data were analyzed using structural equation modeling.
      RESULTS: The results showed that family relations is positively correlated with
      happiness, sense of coherence and perceived health. The results also showed that
      good family relations and a sense of coherence predict greater happiness. The
      results from structure equation modeling showed that the relationship between
      family relations and perceived health is completely mediated by happiness and a
      sense of coherence, but only the indirect effect of happiness is significant. The
      results also showed that family relations is partially mediated by the sense of
      coherence to happiness. CONCLUSIONS: In caring for retired older people, medical
      professionals need to increase their family relations and sense of coherence
      simultaneously, and then promote happiness in their interventions. Geriatr
      Gerontol Int 2018; 18: 154-160.

PMID- 28753240
TI  - Risk of early, intermediate, and late rejection following heart transplantation:
      Trends over the past 25 years and relation to changes in medical management.
      Tertiary center experience: The Sheba Heart Transplantation Registry.
AB  - AIM: To explore the trends in the risk for rejection following heart
      transplantation (HT) over the past 25 years, and their relation to changes in
      medical management. METHODS: The study population comprised 216 HT patients.
      Rejection periods were defined as follows: 0-3 months (early), 3-12 months
      (intermediate), and 12+ months (late). HT era was dichotomized as follows: 1991
      1999 (remote era) and 2000-2016 (recent era). Medication combination was
      categorized as newer (TAC, MMF, and everolimus) vs older therapies (AZA, CSA).
      RESULTS: Multivariate analysis showed that patients who underwent HT during the
      recent era experienced a significant reduction in the risk for major rejection.
      These findings were consistent for early (OR = 0.44 [95% CI 0.22-0.88]),
      intermediate (OR = 0.02 [95% CI 0.003-0.11]), and late rejections (OR = 0.18 [95%
      CI 0.05-0.52]). Using the year of HT as a continuous measure showed that each 1
      year increment was independently associated with a significant reduction in the
      risk for early, intermediate, and late rejections (5%, 21%, 18%, respectively).
      In contrast, the risk reduction associated with newer types of immunosuppressive
      therapies was not statistically significant after adjustment for the treatment
      period. CONCLUSIONS: Major rejection rates following HT have significantly
      declined over the past 2 decades even after adjustment for changes in
      immunosuppressive therapies, suggesting that other factors may also play a role
      in the improved outcomes of HT recipients.

PMID- 28753241
TI  - The importance of immunization in cancer prevention, treatment, and survivorship.
AB  - Answer questions and earn CME/CNE A measles outbreak originating in California
      during 2014 and 2015 called attention to the potential for infectious disease
      outbreaks related to underimmunized populations in the United States and the
      potential risk to pediatric patients with cancer attending school when such
      outbreaks occur. Compliance with vaccine recommendations is important for the
      prevention of hepatitis B-related and human papillomavirus-related cancers and
      for protecting immunocompromised patients with cancer, and these points are often
      overlooked, resulting in the continued occurrence of vaccine-preventable
      neoplastic and infectious diseases and complications. This article provides an
      overview of the importance of vaccines in the context of cancer and encourages
      clinician, health system, and public policy efforts to promote adherence to
      immunization recommendations in the United States. CA Cancer J Clin 2017;67:398
      410. (c) 2017 American Cancer Society.

PMID- 28753242
TI  - Investigation of pain and life satisfaction in older adults.
AB  - AIM: The present study aimed to investigate pain and life satisfaction in older
      adults. METHODS: This study, which is descriptive in nature, utilized the
      relational screening model. It was carried out between September 2016 and March
      2017, with 387 people aged >=65 years who were registered in Family Health
      Centers in Agri, a city located in eastern Turkey. RESULTS: The participants'
      mean Geriatric Pain Measure score was 53.23 +/- 29.40, indicating moderate pain.
      The mean Life Satisfaction Scale score was 8.50 +/- 5.34, indicating moderate
      life satisfaction level. The study also found a statistically significant,
      negative relationship between life satisfaction and geriatric pain. CONCLUSIONS:
      An increase in the elderly population brings various health problems. The results
      of the present study showed that the rate of chronic diseases is very high in
      older adults. Therefore, pain is one of the most frequently encountered health
      problems, and it has negative effects on life satisfaction. In conclusion, is it
      considered that older adults' life satisfaction could increase if their pain is
      identified and reduced effectively. Geriatr Gerontol Int 2018; 18: 5-11.

PMID- 28753243
TI  - A seroepidemiological survey of the effect of hepatitis B vaccine and hepatitis B
      and C virus infections among elementary school students in Siem Reap province,
      Cambodia.
AB  - AIM: This study aimed to survey the prevalence and incidence of hepatitis B (HBV)
      and hepatitis C virus (HCV) infection among elementary school students in Siem
      Reap province, Cambodia and to evaluate the effects of a national infant HBV
      vaccination program introduced in 2001. METHODS: Students in 3rd grade during the
      2011, 2012, and 2013 academic years were enrolled in this study; at the time of
      the second examination, in the 2014-2015 academic year, the students were in 5th
      or 6th grade. The incidence and prevalence rates of HBV and HCV infection were
      estimated and full HBV sequences were analyzed. RESULTS: Among 248 students (107
      male and 141 female) born between 1999 and 2005, five students were HBV surface
      antigen (HBs-Ag) positive (2.02%), and all of them were infected with genotype C.
      Among them, subgenotype C1 was found in four students and, unexpectedly, complete
      genetic sequence identity of subgenotype C1 was found in two students from
      different families. The anti-HBV core (HBc) and anti-HBs prevalence rates were
      10.89% and 16.13%, respectively. Twenty-five students were positive for anti-HBs
      and negative for both HBsAg and anti-HBc (10.08%; estimated serological
      vaccination rate); this rate increased significantly with the birth year (P =
      0.0229). Prevalence of anti-HCV was 2.82%, and HCV RNA was not detected. The
      estimated incidence of HBV and HCV infection were both 0/1000 person-years (PY)
      (95% confidence interval, 0-20.61/1000 PY and 0-14.50/1000 PY, respectively).
      CONCLUSION: Hepatitis B virus full-genome sequencing and serological analysis
      revealed the possibility of horizontal transmission of HBV among Cambodian
      schoolchildren. However, the anti-HBc positivity rate decreased along with
      increasing age and estimated serological vaccination rates.

PMID- 28753244
TI  - Functional characterization of the transcriptional regulatory elements of three
      highly expressed constitutive genes in the jewel wasp, Nasonia vitripennis.
AB  - The jewel wasp, Nasonia vitripennis Ashmead (Hymenoptera: Pteromalidae), is an
      easily reared parasitoid that is providing an ever increasingly malleable model
      for examining the biology and genetics of Hymenoptera. Utilizing genomic and
      transcriptome resources, 5' upstream transcriptional regulatory sequences (TREs)
      from three highly expressed genes were identified and cloned. Criteria for TRE
      selection included the presence of an adjacent gene 5' of the translation
      initiation site. One gene was methylated whereas the other two were
      nonmethylated. Each TRE, heat-shock protein 70 (hsp70), activator of 90 kDa hsp
      ATPase protein 1 (hsp90A), and lipid storage droplet surface-binding protein 1
      (lsdp) was linked with enhanced green fluorescent protein (EGFP) coding sequence
      and cloned into both pDP9e somatic and piggyBac germline transformation vectors.
      EGFP expression patterns under control of each TRE were compared with patterns of
      DsRed fluorescence produced from the transformation vector cassette. Functional
      activity of each TRE was observed in cultured Spodoptera frugiperda 9 (Sf9) cells
      and Drosophila melanogaster as well as in N. vitripennis embryos demonstrating
      that all three sequences had functional transcriptional regulatory activity in
      three different insect orders. Identification and functional characterization of
      these three TREs will provide critical and necessary resources for further
      genetic analyses of N. vitripennis, Hymenoptera and other insects.

PMID- 28753245
TI  - Selective 19 F-Labeling of Functionalized Carboxylic Acids with Difluoromethyl
      Diazomethane (CF2 HCHN2 ).
AB  - The incorporation of fluorinated moieties into organic structures is a
      particularly powerful approach for generating compounds with useful biological
      applications in industry, pharmacology, and agriculture. Here, the recently
      developed reagent-CF2 HCHN2 -selectively esterifies carboxyl groups on organic
      molecules in the presence of other polar functional groups. The reaction is
      remarkably simple, proceeding at room temperature in chloroform without addition
      of a catalyst. The procedure allows "last-step" incorporation of a fluorinated
      ester moiety into organic structures, including bioorganic molecules such as
      peptides and proteins. The fluorinated ester can subsequently function as a 19 F
      probe in biomolecules, thereby enabling molecular size determination by diffusion
      19 F NMR experiments.

PMID- 28753246
TI  - Outcome of prenatally diagnosed congenital lung anomalies in the North of
      England: a review of 228 cases to aid in prenatal counselling.
AB  - OBJECTIVE: To describe data on congenital lung anomalies identified on prenatal
      ultrasound from two centres in the North of England. METHOD: This retrospective
      case series includes all cases notified to the Northern Congenital Abnormality
      Survey from 1990 to 2010 and to Leeds Regional Fetal Medicine Unit 2000-2015.
      RESULTS: There were a total of 228 cases, 101 from Northern Congenital
      Abnormality Survey and 127 from Leeds Regional Fetal Medicine Unit. Eight-five
      per cent were unilateral congenital pulmonary airway malformations (CPAMs), 2%
      bilateral CPAMs and 11% bronchopulmonary sequestrations. Mediastinal shift was
      present in 50% of cases, occurring more frequently in macrocystic CPAMs and
      larger lesions. Polyhydramnios was evident in 28%, and fetal hydrops occurred in
      9%. Prenatal regression occurred in 54%, and lesions were no longer visible on
      ultrasound in 27% at a later gestation. Prenatal intervention was performed in 5%
      of cases, and postnatal surgical intervention was required in 12% due to ongoing
      respiratory symptoms. Regression of fetal hydrops occurred in five cases.
      CONCLUSION: The outcome was favourable in 83% cases. Prenatal regression was
      common, and macrocystic lesions were less likely to regress than microcystic
      lesions. No specific prenatal features predicted the need for early surgical
      intervention. The data analysed in this prenatal series will help when
      counselling prenatal cases. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28753247
TI  - Take away body parts! An investigation into the use of 3D-printed anatomical
      models in undergraduate anatomy education.
AB  - Understanding the three-dimensional (3D) nature of the human form is imperative
      for effective medical practice and the emergence of 3D printing creates numerous
      opportunities to enhance aspects of medical and healthcare training. A recently
      deceased, un-embalmed donor was scanned through high-resolution computed
      tomography. The scan data underwent segmentation and post-processing and a range
      of 3D-printed anatomical models were produced. A four-stage mixed-methods study
      was conducted to evaluate the educational value of the models in a medical
      program. (1) A quantitative pre/post-test to assess change in learner knowledge
      following 3D-printed model usage in a small group tutorial; (2) student focus
      group (3) a qualitative student questionnaire regarding personal student model
      usage (4) teaching faculty evaluation. The use of 3D-printed models in small
      group anatomy teaching session resulted in a significant increase in knowledge (P
      = 0.0001) when compared to didactic 2D-image based teaching methods. Student
      focus groups yielded six key themes regarding the use of 3D-printed anatomical
      models: model properties, teaching integration, resource integration, assessment,
      clinical imaging, and pathology and anatomical variation. Questionnaires detailed
      how students used the models in the home environment and integrated them with
      anatomical learning resources such as textbooks and anatomy lectures. In
      conclusion, 3D-printed anatomical models can be successfully produced from the CT
      data set of a recently deceased donor. These models can be used in anatomy
      education as a teaching tool in their own right, as well as a method for
      augmenting the curriculum and complementing established learning modalities, such
      as dissection-based teaching. Anat Sci Educ 11: 44-53. (c) 2017 American
      Association of Anatomists.

PMID- 28753249
TI  - A new approach to specific IgE testing, asthma and auto-injectors in schools.

PMID- 28753250
TI  - Idiosyncratic responses to climate-driven forest fragmentation and marine
      incursions in reed frogs from Central Africa and the Gulf of Guinea Islands.
AB  - Organismal traits interact with environmental variation to mediate how species
      respond to shared landscapes. Thus, differences in traits related to dispersal
      ability or physiological tolerance may result in phylogeographic discordance
      among co-distributed taxa, even when they are responding to common barriers. We
      quantified climatic suitability and stability, and phylogeographic divergence
      within three reed frog species complexes across the Guineo-Congolian forests and
      Gulf of Guinea archipelago of Central Africa to investigate how they responded to
      a shared climatic and geological history. Our species-specific estimates of
      climatic suitability through time are consistent with temporal and spatial
      heterogeneity in diversification among the species complexes, indicating that
      differences in ecological breadth may partly explain these idiosyncratic
      patterns. Likewise, we demonstrated that fluctuating sea levels periodically
      exposed a land bridge connecting Bioko Island with the mainland Guineo-Congolian
      forest and that habitats across the exposed land bridge likely enabled dispersal
      in some species, but not in others. We did not find evidence that rivers are
      biogeographic barriers across any of the species complexes. Despite marked
      differences in the geographic extent of stable climates and temporal estimates of
      divergence among the species complexes, we recovered a shared pattern of
      intermittent climatic suitability with recent population connectivity and
      demographic expansion across the Congo Basin. This pattern supports the
      hypothesis that genetic exchange across the Congo Basin during humid periods,
      followed by vicariance during arid periods, has shaped regional diversity.
      Finally, we identified many distinct lineages among our focal taxa, some of which
      may reflect incipient or unrecognized species.

PMID- 28753251
TI  - Liraglutide mitigates TNF-alpha induced pro-atherogenic changes and microvesicle
      release in HUVEC from diabetic women.
AB  - BACKGROUND: To evaluate whether exposure to GLP-1 receptor agonist Liraglutide
      could modulate pro-atherogenic alterations previously observed in endothelial
      cells obtained by women affected by gestational diabetes (GD), thus exposed in
      vivo to hyperglycemia, oxidative stress, and inflammation and to evaluate
      endothelial microvesicle (EMV) release, a new reliable biomarker of vascular
      stress/damage. METHODS: We studied Liraglutide effects and its plausible
      molecular mechanisms on monocyte cell adhesion and adhesion molecule expression
      and membrane exposure in control (C-) human umbilical vein endothelial cells
      (HUVEC) as well as in HUVEC of women affected by GD exposed in vitro to TNF
      alpha. In the same model, we also investigated Liraglutide effects on EMV
      release. RESULTS: In response to TNF-alpha, endothelial monocyte adhesion and
      VCAM-1 and ICAM-1 expression and exposure on plasma membrane was greater in GD
      HUVEC than C-HUVEC. This was the case also for EMV release. In GD-HUVEC,
      Liraglutide exposure significantly reduced TNF-alpha induced endothelial monocyte
      adhesion as well as VCAM-1 and ICAM-1 expression and exposure on plasma membrane.
      In the same cells, Liraglutide exposure also reduced MAPK/NF-kB activation,
      peroxynitrite levels, and EMV release. CONCLUSIONS: TNF-alpha induced pro
      atherogenic alterations are amplified in endothelial cells chronically exposed to
      hyperglycemia in vivo. Liraglutide mitigates TNF-alpha effects and reduces cell
      stress/damage indicators, such as endothelial microvesicle (EMV) release. These
      results foster the notion that Liraglutide could exert a protective effect
      against hyperglycemia and inflammation triggered endothelial dysfunction.

PMID- 28753253
TI  - Clear-cell atypical fibroxanthoma: An unusual case in an unusual place.
AB  - Atypical fibroxanthoma represents a low-grade sarcoma that usually presents in
      the elderly population on sun-damaged areas of the head and neck regions. This
      neoplasm is characterized on histology by atypical pleomorphic, epithelioid to
      spindled cells, arranged in a haphazard pattern, set within a background of solar
      elastosis. In this case report, we present a unique case of the rare variant of
      clear-cell atypical fibroxanthoma arising in an unusual place, specifically the
      lower extremities.

PMID- 28753252
TI  - Utility and reproducibility of 3-dimensional printed models in pre-operative
      planning of complex thoracic tumors.
AB  - BACKGROUND AND OBJECTIVES: 3D-printed models are increasingly used for surgical
      planning. We assessed the utility, accuracy, and reproducibility of 3D printing
      to assist visualization of complex thoracic tumors for surgical planning.
      METHODS: Models were created from pre-operative images for three patients using a
      standard radiology 3D workstation. Operating surgeons assessed model utility
      using the Gillespie scale (1 = inferior to 4 = superior), and accuracy compared
      to intraoperative findings. Model variability was assessed for one patient for
      whom two models were created independently. The models were compared subjectively
      by surgeons and quantitatively based on overlap of depicted tissues, and
      differences in tumor volume and proximity to tissues. RESULTS: Models were
      superior to imaging and 3D visualization for surgical planning (mean score =
      3.4), particularly for determining surgical approach (score = 4) and
      resectability (score = 3.7). Model accuracy was good to excellent. In the two
      models created for one patient, tissue volumes overlapped by >86.5%, and tumor
      volume and area of tissues <=1 mm to the tumor differed by <15% and <1.8 cm2 ,
      respectively. Surgeons considered these differences to have negligible effect on
      surgical planning. CONCLUSION: 3D printing assists surgical planning for complex
      thoracic tumors. Models can be created by radiologists using routine practice
      tools with sufficient accuracy and clinically negligible variability.

PMID- 28753254
TI  - Hierarchical Nanotubes Constructed by Carbon-Coated Ultrathin SnS Nanosheets for
      Fast Capacitive Sodium Storage.
AB  - Tin(II) sulfide (SnS) has been an attractive anode material for sodium ion
      batteries. Herein, an elegant templating method has been developed for the
      rational design and synthesis of hierarchical SnS nanotubes composed of ultrathin
      nanosheets. In order to enhance the electrochemical performance, carbon coated
      hierarchical SnS nanotubes (denoted as SnS@C nanotubes) have also been obtained
      by simply adding glucose into the reaction system. Benefiting from their unique
      structural merits, the SnS@C nanotubes exhibit enhanced sodium storage properties
      in terms of good cycling performance and superior rate capability.

PMID- 28753255
TI  - Comprehensive analysis of two Shank3 and the Cacna1c mouse models of autism
      spectrum disorder.
AB  - To expand, analyze and extend published behavioral phenotypes relevant to autism
      spectrum disorder (ASD), we present a study of three ASD genetic mouse models:
      Feng's Shank3tm2Gfng model, hereafter Shank3/F, Jiang's Shank3tm1Yhj model,
      hereafter Shank3/J and the Cacna1c deletion model. The Shank3 models mimick gene
      mutations associated with Phelan-McDermid Syndrome and the Cacna1c model
      recapitulates the deletion underlying Timothy syndrome. This study utilizes both
      standard and novel behavioral tests with the same methodology used in our
      previously published companion report on the Cntnap2 null and 16p11.2 deletion
      models. We found that some but not all behaviors replicated published findings
      and those that did replicate, such as social behavior and overgrooming in Shank3
      models, tended to be milder than reported elsewhere. The Shank3/F model, and to a
      much lesser extent, the Shank3/J and Cacna1c models, showed hypoactivity and a
      general anxiety-like behavior triggered by external stimuli which pervaded social
      interactions. We did not detect deficits in a cognitive procedural learning test
      nor did we observe perseverative behavior in these models. We did, however, find
      differences in exploratory patterns of Cacna1c mutant mice suggestive of a
      behavioral effect in a social setting. In addition, only Shank3/F showed
      differences in sensory-gating. Both positive and negative results from this study
      will be useful in identifying the most robust and replicable behavioral
      signatures within and across mouse models of autism. Understanding these
      phenotypes may shed light of which features to study when screening compounds for
      potential therapeutic interventions.

PMID- 28753256
TI  - A novel moonlight function of glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      for immunomodulation.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an energy metabolism-related
      enzyme, which generates NADH in glycolysis. Our previous study revealed a novel
      role of exogenous GAPDH in the amelioration of lipopolysaccharide (LPS)-induced
      sepsis-related, severe acute lung injury (ALI) in mice. Here, we show the effect
      of extracellular GAPDH on the physiological functions of macrophages, which play
      an important role in the onset of sepsis and ALI. GAPDH has no effect on cell
      viability, while it strongly suppressed cell adhesion, spreading, and phagocytic
      function of LPS-stimulated macrophages. GAPDH treatment significantly reduced
      tumor necrosis factor (TNF)-alpha, while it induced interleukin (IL)-10
      production from LPS-stimulated macrophages in a dose-dependent manner. It is
      noteworthy that heat inactivation of GAPDH lost its immunomodulatory activity.
      Correspondingly, NADH significantly inhibited TNF-alpha and enhanced IL-10
      production with elevation of both M1/M2 macrophage markers. These data suggest
      that extracellular GAPDH induces intermediate M1/M2 macrophages for termination
      of inflammation, partly through its enzyme activity for generation of NADH. (c)
      2017 BioFactors, 2017.

PMID- 28753257
TI  - Caffeic acid attenuates the inflammatory stress induced by glycated LDL in human
      endothelial cells by mechanisms involving inhibition of AGE-receptor, oxidative,
      and endoplasmic reticulum stress.
AB  - Type 2 diabetes mellitus is a worldwide epidemic and its atherosclerotic
      complications determine the high morbidity and mortality of diabetic patients.
      Caffeic acid (CAF), a phenolic acid present in normal diets, is known for its
      antioxidant properties. The aim of this study was to investigate CAF's anti
      inflammatory properties and its mechanism of action, using cultured human
      endothelial cells (HEC) incubated with glycated low-density lipoproteins (gLDL).
      Levels of the receptor for advanced glycation end-products (RAGE), inflammatory
      stress markers (C reactive protein, CRP; vascular cell adhesion molecule-1, VCAM
      1; monocyte chemoattractant protein-1, MCP-1), and oxidative stress and
      endoplasmic reticulum stress (ERS) markers were evaluated in gLDL-exposed HEC, in
      the presence/absence of CAF. RAGE silencing or blocking, specific inhibitors for
      oxidative stress (apocynin, N-acetyl-cysteine), and ERS (salubrinal) were used.
      The results showed that: (i) gLDL induced CRP synthesis and secretion through
      mechanisms involving NADPH oxidase-dependent oxidative stress and ERS in HEC;
      (ii) gLDL-RAGE interaction, oxidative stress, and ERS stimulated the secretion of
      VCAM-1 and MCP-1 in HEC; and (iii) CAF reduced the secretion of CRP, VCAM-1, and
      MCP-1 in gLDL-exposed HEC by inhibiting RAGE expression, oxidative stress, and
      ERS. In conclusion, CAF might be a promising alternative to ameliorate a wide
      spectrum of disorders due to its complex mechanisms of action resulting in anti
      inflammatory and antioxidative properties. (c) 2017 BioFactors, 43(5):685-697,
      2017.

PMID- 28753258
TI  - Medicare, Medicaid, and Children's Health Insurance Programs: Announcement of the
      Extension of Temporary Moratoria on Enrollment of Part B Non-Emergency Ground
      Ambulance Suppliers and Home Health Agencies in Designated Geographic Locations.
      Extension of temporary moratoria.
AB  - This document announces the extension of statewide temporary moratoria on the
      enrollment of new Medicare Part B non-emergency ground ambulance providers and
      suppliers and Medicare home health agencies, subunits, and branch locations in
      Florida, Illinois, Michigan, Texas, Pennsylvania, and New Jersey, as applicable,
      to prevent and combat fraud, waste, and abuse. This extension also applies to the
      enrollment of new non-emergency ground ambulance suppliers and home health
      agencies, subunits, and branch locations in Medicaid and the Children's Health
      Insurance Program in those states.

PMID- 28753259
TI  - Medical Devices; Cardiovascular Devices; Classification of the Adjunctive
      Cardiovascular Status Indicator. Final order.
AB  - The Food and Drug Administration (FDA) is classifying the adjunctive
      cardiovascular status indicator into class II (special controls). The special
      controls that will apply to the device are identified in this order and will be
      part of the codified language for the adjunctive cardiovascular status
      indicator's classification. The Agency is classifying the device into class II
      (special controls) in order to provide a reasonable assurance of safety and
      effectiveness of the device.

PMID- 28753260
TI  - Medical Devices; Gastroenterology-Urology Devices; Classification of the Oral
      Removable Palatal Space Occupying Device for Weight Management and/or Weight
      Loss. Final order.
AB  - The Food and Drug Administration (FDA or Agency) is classifying the oral
      removable palatal space occupying device for weight management and/or weight loss
      into class II (special controls). The special controls that will apply to the
      device are identified in this order and will be part of the codified language for
      the oralremovable palatal space occupying device for weight management and/or
      weight loss classification. The Agency is classifying the device into class II
      (special controls) in order to provide a reasonable assurance of safety and
      effectiveness of the device.

PMID- 28753261
TI  - Medical Devices; Neurological Devices; Classification of Cranial Motion
      Measurement Device. Final order.
AB  - The Food and Drug Administration (FDA or Agency) is classifying the cranial
      motion measurement device into class II (special controls). The special
      controlsthat will apply to the device are identified in this order and will be
      part of the codified language for the cranial motion measurement device's
      classification. The Agency is classifying the device into class II (special
      controls) in order to provide a reasonable assurance of safety and effectiveness
      of the device.

PMID- 28753262
TI  - Medical Devices; Obstetrical and Gynecological Devices; Classification of the
      Closed Loop Hysteroscopic Insufflator With Cutter-Coagulator. Final order.
AB  - The Food and Drug Administration (FDA, Agency, or we) is classifying the closed
      loop hysteroscopic insufflator with cutter-coagulator into class II (special
      controls). The special controls that will apply to the device are identified in
      this order, and will be part of the codified language for the closed loop
      hysteroscopic insufflator with cutter-coagulator classification. The Agency is
      classifying the device into class II (special controls) in order to provide a
      reasonable assurance of safety and effectiveness of the device.

PMID- 28753263
TI  - Ultrahigh Detectivity and Wide Dynamic Range Ultraviolet Photodetectors Based on
      BixSn1-xO2 Intermediate Band Semiconductor.
AB  - The ultraviolet (UV) photodetectors have significant applications different
      fields. High detectivity, high responsivity and wide active area are required to
      probe a weak UV light in actual ambient. Unfortunately, most practical UV
      photoconductors based on wide bandgap semiconductor films can hardly have both a
      high responsivity and a low dark current density. In this study, the intermediate
      band engineering in semiconductor has been proposed try to solve this problem.
      The intermediate band UV photodetectors based on BixSn1-xO2 (0.017 < x < 0.041)
      films show a detectivity of 6.1 * 1015 Jones at 280 nm and a quantum efficiency
      of 2.9 * 104 %. The dynamic range is 195 dB, which is much higher than other UV
      photodetector. The recovery time is about 1 s after exposing device into ethanol
      steam. Our results demonstrate that the intermediate band semiconductor BixSn1
      xO2 films can serve as a high performance UV photodetector.

PMID- 28753264
TI  - LipidHunter Identifies Phospholipids by High-Throughput Processing of LC-MS and
      Shotgun Lipidomics Datasets.
AB  - Lipids are dynamic constituents of biological systems, rapidly responding to any
      changes in physiological conditions. Thus, there is a large interest in lipid
      derived markers for diagnostic and prognostic applications, especially in
      translational and systems medicine research. As lipid identification remains a
      bottleneck of modern untargeted lipidomics, we developed LipidHunter, a new open
      source software for the high-throughput identification of phospholipids in data
      acquired by LC-MS and shotgun experiments. LipidHunter resembles a workflow of
      manual spectra annotation. Lipid identification is based on MS/MS data analysis
      in accordance with defined fragmentation rules for each phospholipid (PL) class.
      The software tool matches product and neutral loss signals obtained by collision
      induced dissociation to a user-defined white list of fatty acid residues and PL
      class-specific fragments. The identified signals are tested against elemental
      composition and bulk identification provided via LIPID MAPS search. Furthermore,
      LipidHunter provides information-rich tabular and graphical reports allowing to
      trace back key identification steps and perform data quality control. Thereby,
      202 discrete lipid species were identified in lipid extracts from rat primary
      cardiomyocytes treated with a peroxynitrite donor. Their relative quantification
      allowed the monitoring of dynamic reconfiguration of the cellular lipidome in
      response to mild nitroxidative stress. LipidHunter is available free for download
      at https://bitbucket.org/SysMedOs/lipidhunter .

PMID- 28753265
TI  - Correction to Drug Delivery Systems Based on Hydroxyethyl Starch.

PMID- 28753266
TI  - Evolution of Structural and Electrical Properties of Oxygen-Deficient VO2 under
      Low Temperature Heating Process.
AB  - Structural stability and functional performances of vanadium dioxide (VO2) are
      strongly influenced by oxygen vacancies. However, the mechanism of metal
      insulator transition (MIT) influenced by defects is still under debate. Here, we
      study the evolution of structure and electrical property of oxygen-deficient VO2
      by a low temperature annealing process (LTP) based on a truss-structured VO2
      nanonet. The oxygenation process of the oxygen-deficient VO2 is greatly
      prolonged, which enables us to probe the gradual change of properties of the
      oxygen-deficient VO2. A continuous lattice reduction is observed during LTP. No
      recrystallization and structural collapse of the VO2 nanonet can be found after
      LTP. The valence-band X-ray photoelectron spectroscopy (XPS) measurements
      indicate that the oxygen deficiency strongly affects the energy level of the
      valence band edge. Correspondingly, the resistance changes of the VO2 films from
      1 to 4.5 orders of magnitude are achieved by LTP. The effect of oxygen vacancy on
      the electric field driven MIT is investigated. The threshold value of voltage
      triggering the MIT decreases with increasing the oxygen vacancy concentration.
      This work demonstrates a novel and effective way to control the content of oxygen
      vacancies in VO2 and the obvious impact of oxygen vacancy on MIT, facilitating
      further research on the role of oxygen vacancy in structure and MIT of VO2, which
      is important for the deep understanding of MIT and exploiting innovative
      functional application of VO2.

PMID- 28753267
TI  - Enhancing the Photovoltaic Performance of Perovskite Solar Cells with a Down
      Conversion Eu-Complex.
AB  - Organometal halide perovskite solar cells (PSCs) have shown high photovoltaic
      performance but poor utilization of ultraviolet (UV) irradiation. Lanthanide
      complexes have a wide absorption range in the UV region and they can down-convert
      the absorbed UV light into visible light, which provides a possibility for PSCs
      to utilize UV light for higher photocurrent, efficiency, and stability. In this
      study, we use a transparent luminescent down-converting layer (LDL) of Eu-4,7
      diphenyl-1,10-phenanthroline (Eu-complex) to improve the light utilization
      efficiency of PSCs. Compared with the uncoated PSC, the PSC coated with Eu
      complex LDL on the reverse of the fluorine-doped tin oxide glass displayed an
      enhancement of 11.8% in short-circuit current density (Jsc) and 15.3% in
      efficiency due to the Eu-complex LDL re-emitting UV light (300-380 nm) in the
      visible range. It is indicated that the Eu-complex LDL plays the role of
      enhancing the power conversion efficiency as well as reducing UV degradation for
      PSCs.

PMID- 28753268
TI  - Microscale Mass Spectrometry Analysis of Extracellular Metabolites in Live
      Multicellular Tumor Spheroids.
AB  - Extracellular compounds in tumors play critical roles in intercellular
      communication, tumor proliferation, and cancer cell metastasis. However, the lack
      of appropriate techniques leads to limited studies of extracellular metabolite.
      Here, we introduced a microscale collection device, the Micro-funnel, fabricated
      from biocompatible fused silica capillary. With a small probe size (~25 MUm), the
      Micro-funnel can be implanted into live multicellular tumor spheroids to
      accumulate the extracellular metabolites produced by cancer cells. Metabolites
      collected in the Micro-funnel device were then extracted by a microscale sampling
      and ionization device, the Single-probe, for real-time mass spectrometry (MS)
      analysis. We successfully detected the abundance change of anticancer drug
      irinotecan and its metabolites inside spheroids treated under a series of
      conditions. Moreover, we found that irinotecan treatment dramatically altered the
      composition of extracellular compounds. Specifically, we observed the increased
      abundances of a large number of lipids, which are potentially related to the drug
      resistance of cancer cells. This study provides a novel way to detect the
      extracellular compounds inside live spheroids, and the successful development of
      our technique can benefit the research in multiple areas, including the
      microenvironment inside live tissues, cell-cell communication, biomarker
      discovery, and drug development.

PMID- 28753269
TI  - Highly Sensitive Flexible Pressure Sensor Based on Silver Nanowires-Embedded
      Polydimethylsiloxane Electrode with Microarray Structure.
AB  - Flexible pressure sensors have attracted increasing research interest because of
      their potential applications for wearable sensing devices. Herein, a highly
      sensitive flexible pressure sensor is exhibited based on the elastomeric
      electrodes and a microarray architecture. Polydimethylsiloxane (PDMS) substrate,
      coated with silver nanowires (AgNWs), is used as the top electrode, while
      polyvinylidene fluoride (PVDF) as the dielectric layer. Several transfer
      processes are applied on seeking facile strategy for the preparation of the
      bottom electrode via embedding AgNWs into the PDMS film of microarray structure.
      The flexible pressure sensor integrates the top electrode, dielectric layer, and
      microarray electrode in a sandwich structure. It is demonstrated that such
      sensors possess the superiorities of high sensitivity (2.94 kPa-1), low detection
      limit (<3 Pa), short response time (<50 ms), excellent flexibility, and long-term
      cycle stability. This simple process for preparing such sensors can also be
      easily scaled up to construct pressure sensor arrays for detecting the intensity
      and distribution of the loaded pressure. In addition, this flexible pressure
      sensor exhibits good performance even in a noncontact way, such as detecting
      voice vibrations and air flow. Due to its superior performance, this designed
      flexible pressure sensor demonstrates promising potential in the application of
      electronic skins, as well as wearable healthcare monitors.

PMID- 28753270
TI  - Electronic Properties of a 1D Intrinsic/p-Doped Heterojunction in a 2D Transition
      Metal Dichalcogenide Semiconductor.
AB  - Two-dimensional (2D) semiconductors offer a convenient platform to study 2D
      physics, for example, to understand doping in an atomically thin semiconductor.
      Here, we demonstrate the fabrication and unravel the electronic properties of a
      lateral doped/intrinsic heterojunction in a single-layer (SL) tungsten diselenide
      (WSe2), a prototype semiconducting transition metal dichalcogenide (TMD),
      partially covered with a molecular acceptor layer, on a graphite substrate. With
      combined experiments and theoretical modeling, we reveal the fundamental acceptor
      induced p-doping mechanism for SL-WSe2. At the 1D border between the doped and
      undoped SL-WSe2 regions, we observe band bending and explain it by Thomas-Fermi
      screening. Using atomically resolved scanning tunneling microscopy and
      spectroscopy, the screening length is determined to be in the few nanometer
      range, and we assess the carrier density of intrinsic SL-WSe2. These findings are
      of fundamental and technological importance for understanding and employing
      surface doping, for example, in designing lateral organic TMD heterostructures
      for future devices.

PMID- 28753271
TI  - Efficient Water-Splitting Electrodes Based on Laser-Induced Graphene.
AB  - Electrically splitting water to H2 and O2 is a preferred method for energy
      storage as long as no CO2 is emitted during the supplied electrical input. Here
      we report a laser-induced graphene (LIG) process to fabricate efficient catalytic
      electrodes on opposing faces of a plastic sheet, for the generation of both H2
      and O2. The high porosity and electrical conductivity of LIG facilitates the
      efficient contact and charge transfer with the requisite electrolyte. The LIG
      based electrodes exhibit high performance for hydrogen evolution reaction and
      oxygen evolution reaction with excellent long-term stability. The overpotential
      reaches 100 mA/cm2 for HER, and OER is as low as 214 and 380 mV with relatively
      low Tafel slopes of 54 and 49 mV/dec, respectively. By serial connecting of the
      electrodes with a power source in an O-ring setup, H2 and O2 are simultaneously
      generated on either side of the plastic sheet at a current density of 10 mA/cm2
      at 1.66 V and can thereby be selectively captured. The demonstration provides a
      promising route to simple, efficient, and complete water splitting.

PMID- 28753272
TI  - Colony Lysate Arrays for Proteomic Profiling of Drug-Tolerant Persisters of
      Cancer Cell.
AB  - Functional heterogeneity of cancer cells is one of the key properties to
      understanding relapse after drug treatment. Hence, clarification is needed with
      regard to which types of subgroups of cancer cells dominantly contribute to the
      initiation of relapse. Recently, we established the colony lysate array (CoLA),
      which is a method that allows comparison of individual colonies at the protein
      level to assess the initiation of anticancer drug-tolerant persisters (DTPs)
      based on the reverse-phase protein array (RPPA) system. DTPs grow in various drug
      concentrations and types showing 2-dimensional growth (~1 mm) on a flat surface.
      The size of DTPs are larger than spheroids (~0.3 mm) in agarose gel, which makes
      them easy to handle for a number of assays. DTPs provide functional information
      during the process of their formation, initiating from the origin of a drug
      tolerant single cell. Using >2000 DTPs generated from various drugs and doses
      profiled on the basis of 44 proteins, we demonstrate that the DTPs are clustered
      on the basis of their proteomic profiles changing in response to drugs and doses.
      Of interest, nine transcription factors in the DTPs, such as STAT3 and OCT4A,
      were identified as having decreased or increased levels of proteins in response
      to gefitinib. Importantly, these results can be obtained only by individual
      proteomic colony profiling, which may identify alternative therapeutic targets
      and biomarkers for DTPs that may harbor critical mechanisms for cancer relapse.

PMID- 28753273
TI  - On-Chip Photothermal Analyte Detection Using Integrated Luminescent Temperature
      Sensors.
AB  - Optical absorbance detection based on attenuated light transmission is limited in
      sensitivity due to short path lengths in microfluidic and other miniaturized
      platforms. An alternative is detection using the photothermal effect. Herein we
      introduce a new kind of photothermal absorbance measurement using integrated
      luminescent temperature sensor spots inside microfluidic channels. The
      temperature sensors were photopolymerized inside the channels from NOA 81 UV
      curable thiolene prepolymer doped with a tris(1,10-phenanthroline)ruthenium(II)
      temperature probe. The polymerized sensing structures were as small as 26 +/- 3
      MUm in diameter and displayed a temperature resolution of better than 0.3 K
      between 20 and 50  degrees C. The absorbance from 532 nm laser excitation of the
      food dye Amaranth as a model analyte was quantified using these spots, and the
      influence of the flow rate, laser power, and concentration was investigated.
      Calibration yielded a linear relationship between analyte concentration and the
      temperature signal in the channels. The limit of detection for the azo-dye
      Amaranth (E123) in this setup was 13 MUM. A minimal detectable absorbance of 3.2
      * 10-3 AU was obtained using an optical path length of 125 MUm in this initial
      study. A microreactor with integrated temperature sensors was then employed for
      an absorbance-based miniaturized nitrite analysis, yielding a detection limit of
      26 MUM at a total assay time of only 75 s. This technique is very promising for
      sensitive, and potentially spatially resolved, optical absorbance detection on
      the micro- and nanoscale.

PMID- 28753274
TI  - Thermally Strained Band Gap Engineering of Transition-Metal Dichalcogenide
      Bilayers with Enhanced Light-Matter Interaction toward Excellent Photodetectors.
AB  - Integration of strain engineering of two-dimensional (2D) materials in order to
      enhance device performance is still a challenge. Here, we successfully
      demonstrated the thermally strained band gap engineering of transition-metal
      dichalcogenide bilayers by different thermal expansion coefficients between 2D
      materials and patterned sapphire structures, where MoS2 bilayers were chosen as
      the demonstrated materials. In particular, a blue shift in the band gap of the
      MoS2 bilayers can be tunable, displaying an extraordinary capability to drive
      electrons toward the electrode under the smaller driven bias, and the results
      were confirmed by simulation. A model to explain the thermal strain in the MoS2
      bilayers during the synthesis was proposed, which enables us to precisely predict
      the band gap-shifted behaviors on patterned sapphire structures with different
      angles. Furthermore, photodetectors with enhancement of 286% and 897% based on
      the strained MoS2 on cone- and pyramid-patterned sapphire substrates were
      demonstrated, respectively.

PMID- 28753275
TI  - Osteoconductive Amine-Functionalized Graphene-Poly(methyl methacrylate) Bone
      Cement Composite with Controlled Exothermic Polymerization.
AB  - Bone cement has found extensive usage in joint arthroplasty over the last 50
      years; still, the development of bone cement with essential properties such as
      high fatigue resistance, lower exothermic temperature, and bioactivity has been
      an unsolved problem. In our present work, we have addressed all of the mentioned
      shortcomings of bone cement by reinforcing it with graphene (GR), graphene oxide
      (GO), and surface-modified amino graphene (AG) fillers. These nanocomposites have
      shown hypsochromic shifts, suggesting strong interactions between the filler
      material and the polymer matrix. AG-based nanohybrids have shown greater
      osteointegration and lower cytotoxicity compared to other nanohybrids as well as
      pristine bone cement. They have also reduced oxidative stress on cells, resulting
      in calcification within 20 days of the implantation of nanohybrids into the
      rabbits. They have significantly reduced the exothermic curing temperature to
      body temperature and increased the setting time to facilitate practitioners,
      suggesting that reaction temperature and settling time can be dynamically
      controlled by varying the concentration of the filler. Thermal stability and
      enhanced mechanical properties have been achieved in nanohybrids vis-a-vis pure
      bone cement. Thus, this newly developed nanocomposite can create natural bonding
      with bone tissues for improved bioactivity, longer sustainability, and better
      strength in the prosthesis.

PMID- 28753276
TI  - Sequencing and Identification of Endogenous Neuropeptides with Matrix-Enhanced
      Secondary Ion Mass Spectrometry Tandem Mass Spectrometry.
AB  - Matrix-enhanced secondary ion mass spectrometry (ME-SIMS) has overcome one of the
      biggest disadvantages of SIMS analysis by providing the ability to detect intact
      biomolecules at high spatial resolution. By increasing ionization efficiency and
      minimizing primary ion beam-induced fragmentation of analytes, ME-SIMS has proven
      useful for detection of numerous biorelevant species, now including peptides. We
      report here the first demonstration of tandem ME-SIMS for de novo sequencing of
      endogenous neuropeptides from tissue in situ (i.e., rat pituitary gland). The
      peptide ions were isolated for tandem MS analysis using a 1 Da mass isolation
      window, followed by collision-induced dissociation (CID) at 1.5 keV in a
      collision cell filled with argon gas, for confident identification of the
      detected peptide. Using this method, neuropeptides up to m/z 2000 were detected
      and sequenced from the posterior lobe of the rat pituitary gland. These results
      demonstrate the potential for ME-SIMS tandem MS development in bottom-up
      proteomics imaging at high-spatial resolution.

PMID- 28753277
TI  - Theoretical S1 <- S0 Absorption Energies of the Anionic Forms of Oxyluciferin by
      Variational Monte Carlo and Many-Body Green's Function Theory.
AB  - The structures of three negatively charged forms (anionic keto-1 and enol-1 and
      dianionic enol-2) of oxyluciferin (OxyLuc), which are the most probable emitters
      responsible for the firefly bioluminescence, have been fully relaxed at the
      variational Monte Carlo (VMC) level. Absorption energies of the S1 <- S0 vertical
      transition have been computed using different levels of theory, such as TDDFT,
      CC2, and many-body Green's function theory (MBGFT). The use of MBGFT, by means of
      the Bethe-Salpeter (BS) formalism, on VMC structures provides results in
      excellent agreement with the value (2.26(8) eV) obtained by action spectroscopy
      experiments for the keto-1 form (2.32 eV). To unravel the role of the quality of
      the optimized ground-state geometry, BS excitation energies have also been
      computed on CASSCF geometries, inducing a non-negligible blue shift (0.08 and
      0.07 eV for keto-1 and enol-1 forms, respectively) with respect to the VMC ones.
      Structural effects have been analyzed in terms of over- or undercorrelation along
      the conjugated bonds of OxyLuc by using different methods for the ground-state
      optimization. The relative stability of the S1 state for the keto-1 and enol-1
      forms depends on the method chosen for the excited-state calculation, thus
      representing a fundamental caveat for any theoretical study on these systems.
      Finally, Kohn-Sham HOMO and LUMO orbitals of enol-2 are (nearly) bound only when
      the dianion is embedded into a solvent (water and toluene in the present work);
      excited-state calculations are therefore meaningful only in the presence of a
      dielectric medium which localizes the electronic density. The combination of VMC
      for the ground-state geometry and BS formalism for the absorption spectra clearly
      outperforms standard TDDFT and quantum chemistry approaches.

PMID- 28753278
TI  - Ligand-Driven Coordination Sphere-Induced Engineering of Hybride Materials
      Constructed from PbCl2 and Bis-Pyridyl Organic Linkers for Single-Component Light
      Emitting Phosphors.
AB  - We report design and structural characterization of six new coordination polymers
      fabricated from PbCl2 and a series of closely related bis-pyridyl ligands LI and
      HLII-HLVI, namely, [Pb2(LI)Cl4]n, [Pb(HLII)Cl2]n.nMeOH, [Pb(HLIII)Cl2]n.0.5
      nMeOH, [Pb2(LIV)Cl3]n, [Pb(HLV)Cl2]n, and [Pb3(LVI)2Cl4]n.nMeOH. The topology of
      the obtained networks is dictated by the geometry of the organic ligand. The
      structure of [Pb2(LI)Cl4]n is constructed from the [PbCl2]n two-dimensional (2D)
      sheets, linked through organic linkers into a three-dimensional framework, which
      exhibits a unique binodal 4,7-connected three-periodic topology named by us as
      sda1. Topological analysis of the 2D metal-organic sheet in [Pb(HLII)Cl2]n.nMeOH
      discloses a binodal 3,4-connected layer topology, regardless of the presence of
      tetrel bonds. A one-dimensional (1D) coordination polymer [Pb(HLIII)Cl2]n.0.5
      nMeOH is considered as a uninodal 2-connected chain. The overall structure of
      [Pb2(LIV)Cl3]n is constructed from dimeric tetranuclear [Pb4(MU3-LIV
      kappa6N:N':N":MU3-O)2(MU4-Cl)(MU2-Cl)2]3+ cationic blocks linked in a zigzag
      manner through bridging MU2-Cl- ligands, yielding a 1D polymeric chain.
      Topological analysis of this chain reveals a unique pentanodal 3,4,4,5,6
      connected chain topology named by us as sda2. The structure of [Pb(HLV)Cl2]n
      exhibits a 1D zigzaglike polymeric chain. Two chains are further linked into a 1D
      gridlike ribbon through the dimeric [Pb2(MU2-Cl)2Cl2] blocks as bridging nodes.
      With the bulkiest ligand HLVI, a 2D layered coordination polymer
      [Pb3(LVI)2Cl4]n.nMeOH is formed, which network, considering all tetrel bonds,
      reveals a unique heptanodal 3,3,3,3,4,5,5-connected layer topology named by us as
      sda3. Compounds [Pb2(LI)Cl4]n, [Pb2(LIV)Cl3]n, and [Pb(HLV)Cl2]n were found to be
      emissive in the solid state at ambient temperature. While blue emission of
      [Pb2(LI)Cl4]n is due to the ligand-centered transitions, bluish-green and white
      luminescence of [Pb2(LIV)Cl3]n and [Pb(HLV)Cl2]n, respectively, was assigned to
      ligand-to-metal charge transfer mixed with metal-centered excited states.
      Molecular as well as periodic calculations were additionally applied to
      characterize the obtained polymers.

PMID- 28753279
TI  - Correction to Selenium Ecotoxicology in Freshwater Lakes Receiving Coal
      Combustion Residual Effluents: A North Carolina Example.

PMID- 28753280
TI  - Nanoparticle-Based Immunochemical Biosensors and Assays: Recent Advances and
      Challenges.
AB  - We review the progress achieved during the recent five years in immunochemical
      biosensors (immunosensors) combined with nanoparticles for enhanced sensitivity.
      The initial part introduces antibodies as classic recognition elements. The
      optical sensing part describes fluorescent, luminescent, and surface plasmon
      resonance systems. Amperometry, voltammetry, and impedance spectroscopy represent
      electrochemical transducer methods; electrochemiluminescence with photoelectric
      conversion constitutes a widely utilized combined method. The transducing options
      function together with suitable nanoparticles: metallic and metal oxides,
      including magnetic ones, carbon-based nanotubes, graphene variants, luminescent
      carbon dots, nanocrystals as quantum dots, and photon up-converting particles.
      These sources merged together provide extreme variability of existing
      nanoimmunosensing options. Finally, applications in clinical analysis (markers,
      tumor cells, and pharmaceuticals) and in the detection of pathogenic
      microorganisms, toxic agents, and pesticides in the environmental field and food
      products are summarized.

PMID- 28753281
TI  - Tetrahedral Copper(II) Complexes with a Labile Coordination Site Supported by a
      Tris-tetramethylguanidinato Ligand.
AB  - A new tridentate N3 ligand (TMG3tach) consisting of cis,cis-1,3,5
      triaminocyclohexane (tach) and three N,N,N',N'-tetramethylguanidino (TMG) groups
      has been developed to prepare copper complexes with a tetrahedral geometry and a
      labile coordination site. Treatment of the ligand with CuIIX2 (X = Cl and Br)
      gave copper(II)-halide complexes, [CuII(TMG3tach)Cl]+ (2Cl) and
      [CuII(TMG3tach)Br]+ (2Br), the structures of which have been determined by X-ray
      crystallographic analysis. The complexes exhibit a four-coordinate structure with
      C3v symmetry, where the labile halide ligand (X) occupies a position on the
      trigonal axis. 2Br was converted to a methoxido-copper(II) complex
      [CuII(TMG3tach)(OMe)](OTf) (2OMe), also having a similar four-coordinate
      geometry, by treating it with an equimolar amount of tetrabutylammonium hydroxide
      in methanol. The methoxido-complex 2OMe was further converted to the
      corresponding phenolato-copper(II) (2OAr) and thiophenolato-copper(II) (2SAr)
      complexes by ligand exchange reactions with the neutral phenol and thiophenol
      derivatives, respectively. The electronic structures of the copper(II) complexes
      with different axial ligands are discussed on the basis of EPR spectroscopy and
      DFT calculations.

PMID- 28753282
TI  - Ethylene Epoxidation at the Phase Transition of Copper Oxides.
AB  - Catalytic materials tend to be metastable. When a material becomes metastable
      close to a thermodynamic phase transition it can exhibit unique catalytic
      behavior. Using in situ photoemission spectroscopy and online product analysis,
      we have found that close to the Cu2O-CuO phase transition there is a boost in
      activity for a kinetically driven reaction, ethylene epoxidation, giving rise to
      a 20-fold selectivity enhancement relative to the selectivity observed far from
      the phase transition. By tuning conditions toward low oxygen chemical potential,
      this metastable state and the resulting enhanced selectivity can be sustained.
      Using density functional theory, we find that metastable O precursors to the CuO
      phase can account for the selectivity enhancements near the phase transition.

PMID- 28753283
TI  - Assessing Statistical Uncertainties of Rare Events in Reactive Molecular Dynamics
      Simulations.
AB  - Reactive molecular dynamics (MD) simulations are a versatile tool which allow for
      studying reaction pathways and rates simultaneously. However, most reactions will
      be observed only a few times in such a simulation due to computational
      limitations or slow kinetics, and it is unclear how this will influence the
      obtained rate constants. Therefore, we propose a method based on the Poisson
      distribution to assess the statistical uncertainty of reaction rate constants
      obtained from reactive MD simulations.

PMID- 28753284
TI  - Exploring the Role of Persulfate in the Activation Process: Radical Precursor
      Versus Electron Acceptor.
AB  - This study elucidates the mechanism behind persulfate activation by exploring the
      role of various oxyanions (e.g., peroxymonosulfate, periodate, and peracetate) in
      two activation systems utilizing iron nanoparticle (nFe0) as the reducing agent
      and single-wall carbon nanotubes (CNTs) as electron transfer mediators. Since the
      tested oxyanions serve as both electron acceptors and radical precursors in most
      cases, oxidative degradation of organics was achievable through one-electron
      reduction of oxyanions on nFe0 (leading to radical-induced oxidation) and
      electron transfer mediation from organics to oxyanions on CNTs (leading to
      oxidative decomposition involving no radical formation). A distinction between
      degradative reaction mechanisms of the nFe0/oxyanion and CNT/oxyanion systems was
      made in terms of the oxyanion consumption efficacy, radical scavenging effect,
      and EPR spectral analysis. Statistical study of substrate-specificity and product
      distribution implied that the reaction route induced on nFe0 varies depending on
      the oxyanion (i.e., oxyanion-derived radical), whereas the similar reaction
      pathway initiates organic oxidation in the CNT/oxyanion system irrespective of
      the oxyanion type. Chronoamperometric measurements further confirmed electron
      transfer from organics to oxyanions in the presence of CNTs, which was not
      observed when applying nFe0 instead.

PMID- 28753285
TI  - Activity and Reactivity of Pyrogenic Carbonaceous Matter toward Organic
      Compounds.
AB  - Pyrogenic carbonaceous matter (PCM) includes environmental black carbon (fossil
      fuel soot, biomass char), engineered carbons (biochar, activated carbon), and
      related materials like graphene and nanotubes. These materials contact organic
      pollutants due to their widespread presence in the environment or through their
      use in various engineering applications. This review covers recent advances in
      our understanding of adsorption and chemical reactions mediated by PCM and the
      links between these processes. It also covers adsorptive processes previously
      receiving little attention and ignored in models such as steric constraints,
      physicochemical effects of confinement in nanopores, pi interactions of aromatic
      compounds with polyaromatic surfaces, and very strong hydrogen bonding of
      ionizable compounds with surface functional groups. Although previous research
      has regarded carbons merely as passive sorbents, recent studies show that PCM can
      promote chemical reactions of sorbed contaminants at ordinary temperature,
      including long-range electron conduction between molecules and between microbes
      and molecules, local redox reactions between molecules, and hydrolysis. PCM may
      itself contain redox-active functional groups that are capable of oxidizing or
      reducing organic compounds and of generating reactive oxygen species (ROS) from
      oxygen, peroxides, or ozone. Amorphous carbons contain persistent free radicals
      that may play a role in observed redox reactions and ROS generation. Reactions
      mediated by PCM can impact the biogeochemical fate of pollutants and lead to
      useful strategies for remediation.

PMID- 28753286
TI  - Species Diversity Hinders Adaptation to Toxicants.
AB  - Environmental toxicants such as pesticides exert strong selection pressure on
      many species. While the resulting development of pesticide resistance in
      agricultural pest species is well-known, reports on the extent of adaptation in
      exposed nontarget species are contradictory. These contradictory reports
      highlight a continuing challenge in understanding the relevant ecological
      mechanisms that facilitate or hinder adaptation to toxicants in the field. Here
      we show that species diversity hinders the adaptation to toxicants. In
      agricultural streams with low diversity, we observed an up to 8-fold increase in
      insecticide tolerance in a total of 17 macroinvertebrate species that was not
      observed in more diverse communities under similar contamination. High species
      diversity occurred independently from adjacent nonpolluted refuge areas.
      Therefore, the low level of adaptation in diverse streams cannot be explained by
      an increased recolonization of sensitive individuals from refuge areas. Instead,
      high intraspecific competition may facilitate the selection for increased
      tolerance in low-diverse communities. In diverse communities, by contrast,
      species interactions may reduce intraspecific competition and, thus, the
      potential for developing toxicant resistance. We suggest that this mechanism may
      be the general case in adaptation to environmental stressors. Additionally, we
      conclude that the current framework for risk assessment of pesticides is not
      protective against selection for tolerant organisms and the associated risk of
      genetic erosion.

PMID- 28753287
TI  - Microbial-Phosphorus-Enabled Synthesis of Phosphide Nanocomposites for Efficient
      Electrocatalysts.
AB  - Transition-metal phosphides have recently been identified as low-cost and
      efficient electrocatalysts that are highly active for the hydrogen evolution
      reaction. Unfortunately, to achieve a controlled phosphidation of nonprecious
      metals toward a desired nanostructure of metal phosphides, the synthetic
      processes usually turned complicated, high-cost, and even dangerous due to the
      reaction chemistry related to different phosphorus sources. It becomes even more
      challenging when considering the integration of those active metal phosphides
      with the structural engineering of their conductive matrix toward a favorable
      architecture for optimized catalytic performance. Herein, we identified that the
      biomass itself could act as an effective synthetic platform for the construction
      of supported metal phosphides by recovering its inner phosphorus upon reacting
      with transition-metals ions, forming well-dispersed, highly active nanoparticles
      of metal phosphides incorporated in the nanoporous carbon matrix, which promised
      high catalytic activity in the hydrogen evolution reaction. Our synthetic
      protocol not only provides a simple and effective strategy for the construction
      of a large variety of highly active nanoparticles of metal phosphides but also
      envisions new perspectives on an integrated utilization of the essential
      ingredients, particularly phosphorus, together with the innate architecture of
      the existing biomass for the creation of functional nanomaterials toward
      sustainable energy development.

PMID- 28753288
TI  - Formation of a New, Strongly Basic Nitrogen Anion by Metal Oxide Modification.
AB  - Development of new hybrid materials having unique and unprecedented catalytic
      properties is a challenge for chemists, and heterogeneous-homogeneous hybrid
      catalysts have attracted much attention because of the preferable and exceptional
      properties that are highly expected to result from combination of the components.
      Base catalysts are widely used in organic synthesis as key materials, and a new
      class of base catalysts has made a large impact from academic and industrial
      viewpoints. Here, a principle for creating a new strong base by hybridization of
      homogeneous and heterogeneous components is presented. It is based on the
      modification of organic compounds with metal oxides by using the acid-base
      property of metal oxides. Based on kinetic and DFT studies, combination of CeO2
      and 2-cyanopyridine drastically enhanced the basicity of 2-cyanopyridine by a
      factor of about 109 (~9 by pKa (in CH3CN)), and the pKa was estimated to be ~21,
      which locates it in the superbase category. 2-Cyanopyridine and CeO2 formed a
      unique adsorption complex via two interaction modes: (i) coordinative interaction
      between the Ce atom of CeO2 and the N atom of the pyridine ring in 2
      cyanopyridine, and (ii) covalent interaction between the surface O atom of CeO2
      and the C atom of the CN group in 2-cyanopyridine by addition of the lattice
      oxygen of CeO2 to the CN group of 2-cyanopyridine. These interactions established
      a new, strongly basic site of N- over the CeO2 surface.

PMID- 28753289
TI  - Correction to New 1H NMR-Based Technique To Determine Epoxide Concentrations in
      Oxidized Oil.

PMID- 28753290
TI  - Ralstonins A and B, Lipopeptides with Chlamydospore-Inducing and Phytotoxic
      Activities from the Plant Pathogen Ralstonia solanacearum.
AB  - Ralstonia solanacearum has an orphan hybrid polyketide synthase-nonribosomal
      peptide synthetase gene cluster. We herein isolate its products (named ralstonins
      A and B) from R. solanacearum and elucidate their structures and biological
      activities. Ralstonins are unusual lipodepsipeptides composed of 11 amino acids
      (containing unique amino acids such as beta-hydroxytyrosine and dehydroalanine)
      and a 3-amino-2-hydroxyoctadecanoic acid, and their production is controlled by
      quorum sensing, a mechanism of bacterial cell-cell communication. Ralstonins
      exhibited chlamydospore-inducing activity and phytotoxicity.

PMID- 28753291
TI  - Intrinsic Hydrophobicity versus Intraguest Interactions in Hydrophobically Driven
      Molecular Recognition in Water.
AB  - Molecular recognition of water-soluble molecules is challenging but can be
      achieved if the receptor possesses a hydrophobic binding interface complementary
      to the guest. When the guest molecule contains more than one hydrophobic group,
      intrahost interactions between the hydrophobes could strongly influence the
      binding of the guest by its host. In a series of ornithine derivatives
      functionalized with aromatic hydrophobes, the most electron-rich compound
      displayed the strongest binding, despite its lowest intrinsic hydrophobicity.

PMID- 28753292
TI  - Synthesis of 11C-Labeled RXR Partial Agonist 1-[(3,5,5,8,8-Pentamethyl-5,6,7,8
      tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic Acid (CBt-PMN) by
      Direct [11C]Carbon Dioxide Fixation via Organolithiation of Trialkyltin Precursor
      and PET Imaging Thereof.
AB  - The retinoid X receptor (RXR) partial agonist 1-[(3,5,5,8,8-pentamethyl-5,6,7,8
      tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (1; CBt-PMN, Emax
      = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system
      (CNS) diseases such as Alzheimer's and Parkinson's diseases based on reports that
      RXR-full agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2
      naphthyl)ethynyl]benzoic acid (bexarotene) shows therapeutic effects on these
      disease in rodent models. Here, we synthesized carbon-11-labeled ([11C]1) as a
      tracer for positron emission tomography (PET) and used it in a PET imaging study
      to examine the brain uptake and biodistribution of 1. We found that 11CO2
      fixation after tin-lithium exchange at -20  degrees C afforded [11C]1. This
      methodology may also be useful for synthesizing 11CO2H-PET tracer derivatives of
      other compounds bearing pi-rich heterocyclic rings. A PET/CT imaging study of
      [11C]1 in mice indicated 1 is distributed to the brain and is thus a candidate
      for treatment of CNS diseases.

PMID- 28753293
TI  - Acid/Salt/pH Gradient Improved Resolution and Sensitivity in Proteomics Study
      Using 2D SCX-RP LC-MS.
AB  - The usage of strong cation exchange (SCX) chromatography in proteomics is limited
      by its poor resolution and nonspecific hydrophobic interactions with peptides,
      which lead to peptide overlap across fractions and change of peptide retention,
      respectively. The application of high concentration of salt (up to 1000 mM) in
      SCX also restricted its use in online 2D SCX-RP LC. In the present research, we
      first exploited the chromatographic ability of online 2D SCX-RP LC by combination
      of acid, salt, and pH gradient, three relatively independent modes of eluting
      peptides from SCX column. 50% ACN was added to elution buffer for eliminating
      hydrophobic interactions between SCX matrix and peptides, and the concentration
      of volatile salt was reduced to 50 mM. Acid/salt/pH gradient showed superior
      resolution and sensitivity as well as uniform distribution across fractions,
      consequently leading to significant improvements in peptide and protein
      identification. 112 191 unique peptides and 7373 proteins were identified by
      acid/salt/pH fractionation, while 69 870 unique peptides and 4536 proteins were
      identified by salt elution, that is, 62.5 and 60.6% more proteins and unique
      peptides, respectively, identified by the former. Fraction overlap was also
      significantly minimized by acid/salt/pH approach. Furthermore, acid/salt/pH
      elution showed more identification for acidic peptides and hydrophilic peptides.

PMID- 28753294
TI  - Electrophilic Triterpenoid Enones: A Comparative Thiol-Trapping and Bioactivity
      Study.
AB  - Bardoxolone methyl (1) is the quintessential member of triterpenoid
      cyanoacrylates, an emerging class of bioactive compounds capable of transient
      covalent binding to thiols. The mechanistic basis for this unusual "pulsed
      reactivity" profile and the mode of its biological translation are unknown. To
      provide clues on these issues, a series of Delta1-dehydrooleanolates bearing an
      electron-withdrawing group at C-2 (7a-m) were prepared from oleanolic acid (3a)
      and comparatively investigated in terms of reactivity with thiols and bioactivity
      against a series of electrophile-sensitive transcription factors (Nrf2, NF
      kappaB, STAT3). The emerging picture suggests that the triterpenoid scaffold
      sharply decreases the reactivity of the enone system by steric encumbrance and
      that only strongly electrophilic and sterically undemanding substituents such as
      a cyanide or a carboxylate group can re-establish Michael reactivity, albeit in a
      transient way for the cyanide group. In general, a substantial dissection between
      the thiol-trapping ability and the modulation of biological end-points sensitive
      to thiol alkylation was observed, highlighting the role of shape complementarity
      for the activity of triterpenoid thia-Michael acceptors.

PMID- 28753295
TI  - Empirical Correction for Differences in Chemical Exchange Rates in Hydrogen
      Exchange-Mass Spectrometry Measurements.
AB  - A barrier to the use of hydrogen exchange-mass spectrometry (HX-MS) in many
      contexts, especially analytical characterization of various protein therapeutic
      candidates, is that differences in temperature, pH, ionic strength, buffering
      agent, or other additives can alter chemical exchange rates, making HX data
      gathered under differing solution conditions difficult to compare. Here, we
      present data demonstrating that HX chemical exchange rates can be substantially
      altered not only by the well-established variables of temperature and pH but also
      by additives including arginine, guanidine, methionine, and thiocyanate. To
      compensate for these additive effects, we have developed an empirical method to
      correct the hydrogen-exchange data for these differences. First, differences in
      chemical exchange rates are measured by use of an unstructured reporter peptide,
      YPI. An empirical chemical exchange correction factor, determined by use of the
      HX data from the reporter peptide, is then applied to the HX measurements
      obtained from a protein of interest under different solution conditions. We
      demonstrate that the correction is experimentally sound through simulation and in
      a proof-of-concept experiment using unstructured peptides under slow-exchange
      conditions (pD 4.5 at ambient temperature). To illustrate its utility, we applied
      the correction to HX-MS excipient screening data collected for a pharmaceutically
      relevant IgG4 mAb being characterized to determine the effects of different
      formulations on backbone dynamics.

PMID- 28753296
TI  - Transfer of Dyes and Drugs into Cells Using EGFR-Targeted Nanosyringes.
AB  - Selective targeting of drug loaded nanovectors to specific epitopes highly
      expressed on the surface of cancer cells is a goal for nanotechnologists. We have
      modified our previously described PEGylated-hydrophilic carbon clusters (PEG
      HCCs) so that the epidermal growth factor receptor (EGFR) binding peptide, GE11,
      is attached using click chemistry at the end of each PEG. The resulting
      nanosyringe, PepEGFR-PEG-HCC, can be loaded with a wide range of hydrophobic
      drugs and dyes. We show that, both in vitro and in vivo, this payload can be
      delivered to cancer cells expressing EGFR. We can observe the activation of EGFR
      and track the normal physiological internalization and recycling/signaling
      pathways of this tyrosine kinase following binding of PepEGFR-PEG-HCC. We also
      demonstrate the competitive binding of the nanosyringe to EGFR with its normal
      activator, EGF, as well as observing the colocalization of the nanosyringe with
      clathrin, the coated pit integral protein. The internalization of the drug/dye
      loaded nanosyringe can be inhibited by using anti-EGFR antibodies, the drug
      erlotinib, or Pitstop-1, the clathrin coated pit formation specific inhibitor. To
      further demonstrate the specificity of the drug loaded nanovectors, we
      demonstrated that, in both flank and intracranial xenograft mouse models, dye
      delivery is highly specific to tumors and no other tissues. Finally, using
      nanosyringes loaded with esterase sensitive fluorescein diacetate, we
      demonstrated that the drug payloads can be in vivo delivered to the cytosol of
      cancer cells within the mouse brain.

PMID- 28753297
TI  - Cascade C?O/C?C/C-N Bond Formation: Metal-Free Reactions of 1,4-Diynes and 1-En-4
      yn-3-ones with Isoquinoline and Quinoline N-Oxides.
AB  - The metal-free reactions of 1,4-diynes and 1-en-4-yn-3-ones with isoquinoline and
      quinoline N-oxides are developed, resulting in the formation of 3,4-dihydro-2H
      pyrido[2,1-a]isoquinolines and 2,3-dihydro-1H-pyrido[1,2-a]quinolines via cascade
      C?O/C?C/C-N bond formation. It is the first report in which in the alkyne
      oxidation by N-oxides both the oxygen atom of N-oxides and the nitrogen atom are
      involved in a second C-heteroatom bond formation. The reactions showed a broad
      substrate scope and functional group tolerance. Furthermore, the products were
      found to display green-blue fluorescence in DMSO with fluorescence quantum yields
      up to 0.59.

PMID- 28753298
TI  - Toward Safe Lithium Metal Anode in Rechargeable Batteries: A Review.
AB  - The lithium metal battery is strongly considered to be one of the most promising
      candidates for high-energy-density energy storage devices in our modern and
      technology-based society. However, uncontrollable lithium dendrite growth induces
      poor cycling efficiency and severe safety concerns, dragging lithium metal
      batteries out of practical applications. This review presents a comprehensive
      overview of the lithium metal anode and its dendritic lithium growth. First, the
      working principles and technical challenges of a lithium metal anode are
      underscored. Specific attention is paid to the mechanistic understandings and
      quantitative models for solid electrolyte interphase (SEI) formation, lithium
      dendrite nucleation, and growth. On the basis of previous theoretical
      understanding and analysis, recently proposed strategies to suppress dendrite
      growth of lithium metal anode and some other metal anodes are reviewed. A section
      dedicated to the potential of full-cell lithium metal batteries for practical
      applications is included. A general conclusion and a perspective on the current
      limitations and recommended future research directions of lithium metal batteries
      are presented. The review concludes with an attempt at summarizing the
      theoretical and experimental achievements in lithium metal anodes and endeavors
      to realize the practical applications of lithium metal batteries.

PMID- 28753299
TI  - Excitation Energy Delocalization and Transfer to Guests within MII4L6 Cage
      Frameworks.
AB  - We have prepared a series of MII4L6 tetrahedral cages containing one or the other
      of two distinct BODIPY moieties, as well as mixed cages that contain both BODIPY
      chromophores. The photophysical properties of these cages and their fullerene
      encapsulated adducts were studied in depth. Upon cage formation, the charge
      transfer character exhibited by the bis(aminophenyl)-BODIPY subcomponents
      disappeared. Strong excitonic interactions were instead observed between at least
      two BODIPY chromophores along the edges of the cages, arising from the electronic
      delocalization through the metal centers. This excited-state delocalization
      contrasts with previously reported cages. All cages exhibited the same
      progression from an initial bright singlet state (species I) to a delocalized
      dark state (species II), driven by interactions between the transition dipoles of
      the ligands, and subsequently into geometrically relaxed species III. In the case
      of cages loaded with C60 or C70 fullerenes, ultrafast host-to-guest electron
      transfer was observed to compete with the excitonic interactions, short
      circuiting the I -> II -> III sequence.

PMID- 28753300
TI  - Regioselective Ene-Type Allylic Chlorination of Electron-Rich Alkenes by
      Activated DMSO.
AB  - A simple protocol involving the activation of DMSO by chlorotrimethysilane is
      described for the chemoselective chlorination of polyprenoids. The proposed
      protocol provides a versatile and scalable alternative to existing routes for
      accessing useful synthetic synthons for the synthesis of complex terpenoids.

PMID- 28753301
TI  - Magnesium Oxide Embedded Nitrogen Self-Doped Biochar Composites: Fast and High
      Efficiency Adsorption of Heavy Metals in an Aqueous Solution.
AB  - Lead (Pb) pollution in natural water bodies is an environmental concern due to
      toxic effects on aquatic ecosystems and human health, while adsorption is an
      effective approach to remove Pb from the water. Surface interactions between
      adsorbents and adsorbates play a dominant role in the adsorption process, and
      properly engineering a material's surface property is critical to the improvement
      of adsorption performance. In this study, the magnesium oxide (MgO) nanoparticles
      stabilized on the N-doped biochar (MgO@N-biochar) were synthesized by one-pot
      fast pyrolysis of an MgCl2-loaded N-enriched hydrophyte biomass as a way to
      increase the exchangeable ions and N-containing functional groups and facilitate
      the adsorption of Pb2+. The as-synthesized MgO@N-biochar has a high performance
      with Pb in an aqueous solution with a large adsorption capacity (893 mg/g), a
      very short equilibrium time (<10 min), and a large throughput (~4450 BV). Results
      show that this excellent adsorption performance can be maintained with various
      environmentally relevant interferences including pH, natural organic matter, and
      other metal ions, suggesting that the material may be suitable for the treatment
      of wastewater, natural bodies of water, and even drinking water. In addition,
      MgO@N-biochar quickly and efficiently removed Cd2+ and tetracycline. Multiple
      characterizations and comparative tests have been performed to demonstrate the
      surface adsorption and ion exchange contributed to partial Pb adsorption, and it
      can be inferred from these results that the high performance of MgO@N-biochar is
      mainly due to the surface coordination of Pb2+ and C?O or O?C-O, pyridinic,
      pyridonic, and pyrrolic N. This work suggests that engineering surface functional
      groups of biochar may be crucial for the development of high performance heavy
      metal adsorbents.

PMID- 28753302
TI  - Evidence for a 1,3-Dipolar Cyclo-addition Mechanism in the Decarboxylation of
      Phenylacrylic Acids Catalyzed by Ferulic Acid Decarboxylase.
AB  - Ferulic acid decarboxylase catalyzes the decarboxylation of phenylacrylic acid
      using a newly identified cofactor, prenylated flavin mononucleotide (prFMN). The
      proposed mechanism involves the formation of a putative pentacyclic intermediate
      formed by a 1,3 dipolar cyclo-addition of prFMN with the alpha-beta double bond
      of the substrate, which serves to activate the substrate toward decarboxylation.
      However, enzyme-catalyzed 1,3 dipolar cyclo-additions are unprecedented and other
      mechanisms are plausible. Here we describe the use of a mechanism-based
      inhibitor, 2-fluoro-2-nitrovinylbenzene, to trap the putative cyclo-addition
      intermediate, thereby demonstrating that prFMN can function as a dipole in a 1,3
      dipolar cyclo-addition reaction as the initial step in a novel type of enzymatic
      reaction.

PMID- 28753303
TI  - Engineering the Re-Entrant Hierarchy and Surface Energy of PDMS-PVDF Membrane for
      Membrane Distillation Using a Facile and Benign Microsphere Coating.
AB  - To consolidate the position of membrane distillation (MD) as an emerging membrane
      technology that meets global water challenges, it is crucial to develop membranes
      with ideal material properties. This study reports a facile approach for a
      polyvinylidene fluoride (PVDF) membrane surface modification that is achieved
      through the coating of the surface with poly(dimethylsiloxane) (PDMS) polymeric
      microspheres to lower the membrane surface energy. The hierarchical surface of
      the microspheres was built without any assistance of a nano/microcomposite by
      combining the rapid evaporation of tetrahydrofuran (THF) and the phase separation
      from condensed water vapor. The fabricated membrane exhibited superhydrophobicity
      a high contact angle of 156.9 degrees  and a low contact-angle hysteresis of 11.3
      degrees -and a high wetting resistance to seawater containing sodium dodecyl
      sulfate (SDS). Compared with the control PVDF-hexafluoropropylene (HFP) single
      layer nanofiber membrane, the proposed fabricated membrane with the polymeric
      microsphere layer showed a smaller pore size and higher liquid entry pressure
      (LEP). When it was tested for the direct-contact MD (DCMD) in terms of the
      desalination of seawater (3.5% of NaCl) containing SDS of a progressively
      increased concentration, the fabricated membrane showed stable desalination and
      partial wetting for the 0.1 and 0.2 mM SDS, respectively.

PMID- 28753304
TI  - Proton-Conductivity Enhancement in Polymer Thin Films.
AB  - Highly proton conductive polymers have long attracted the attention of
      researchers for use in energy conversion, sensors, catalysts, and other
      applications. From the viewpoint of the scientific history of the creation of
      highly proton conductive polymers, one fundamental approach is based on the
      strategy of phase-segregated structures with strong acid groups. This Feature
      Article presents a new approach to enhancing the proton conductivity of the
      polymer thin films using an interface that can modify the degrees of freedom for
      a polymer structure through interaction between the substrate surface and
      polymers. I introduce suppressed proton conductivity into Nafion thin films and
      then specifically examine the enhancement in proton conductivity by the molecular
      orientation of the polymers. As the last topic, a highly proton conductive
      organized polyimide thin film is demonstrated using the lyotropic liquid-crystal
      property. Both molecular ordering and the in-plane oriented structure can enhance
      proton conductivity. Moreover, the optical domain and degree of molecular
      ordering derived from the molecular weight can contribute strongly to the proton
      transport property.

PMID- 28753305
TI  - Mimicking a Natural Enzyme System: Cytochrome c Oxidase-Like Activity of Cu2O
      Nanoparticles by Receiving Electrons from Cytochrome c.
AB  - Inorganic nanomaterials-based artificial enzymes (nanozymes) have received
      considerable attention over the past years. However, the substrates studied for
      nanozymes have so far been limited to small organic molecules. The catalytic
      oxidation of biomacromolecules, such as proteins, by nanozymes has not yet been
      reported to date. In this study, we report that cuprous oxide nanoparticles (Cu2O
      NPs) possess cytochrome c oxidase (CcO)-like activity and catalyze the oxidation
      of cytochrome c (Cyt c), converting it from the ferrous state to the ferric state
      under atmospheric oxygen conditions. Furthermore, the CcO-like activity of Cu2O
      NPs is pH- and size-dependent. The lower the solution pH and the smaller the
      particle size, the higher the CcO-like activity. The artificial Cyt c-Cu2O NPs
      system closely mimics the native Cyt c-CcO enzyme system, which opens new vistas
      in enzyme construction and potential applications.

PMID- 28753306
TI  - Novel Hollow Fiber Air Filters for the Removal of Ultrafine Particles in PM2.5
      with Repetitive Usage Capability.
AB  - Severe air pollution has become a global concern, and there is a pressing need to
      develop effective and efficient air filters for removing airborne particulate
      matters (PMs). In this work, a highly permeable poly(ether sulfone) (PES) based
      hollow fiber membrane was developed via a one-step dry-jet wet spinning. For the
      first time, a hollow fiber membrane was used in removing the ultrafine particles
      (PMs with aerodynamic equivalent diameters of less than 100 nm) in PM2.5. The
      novel air filter was designed to possess the synergistic advantages of porous
      filters and fibrous filters with a sievelike outer surface and a fibrouslike
      porous substrate. A filtration efficiency of higher than 99.995% could be easily
      achieved when the self-support hollow fiber was challenged with less than 300 nm
      particulates. Without losses of the structural advantages, we have demonstrated
      that the permeation properties of the hollow fiber membrane can be facilely
      tailored via manipulation of the dope and bore fluid formulations. Various
      cleaning strategies were explored to regenerate the membrane performance after
      fouling. Both water rinse and backwash showed effectiveness to restore the
      membrane permeance for repetitive usage.

PMID- 28753307
TI  - Coumarin versus Chromone Monoamine Oxidase B Inhibitors: Quo Vadis?
AB  - Because of the lack of significant disease-modifying drugs for neurodegenerative
      disorders, a pressing need for new chemical entities endowed with IMAO-B still
      exists. Within this framework, and for the first time, a study was performed to
      compare coumarin- and chomone-3-phenylcarboxamide scaffolds. Compounds 10a and
      10b were the most potent, selective, and reversible noncompetitive IMAO-B. The
      benzopyrone sp2 oxygen atom was found to be position independent and a productive
      contributor for the ligand-enzyme complex stability.

PMID- 28753308
TI  - Assistance of the C-7,8-Picoloyl Moiety for Directing the Glycosyl Acceptors into
      the alpha-Orientation for the Glycosylation of Sialyl Donors.
AB  - An efficient alpha-sialylation method for many primary hydroxyl acceptors that
      include 6-OH glycosides has been developed. 7,8-Di-O-picoloyl sialyl glycoside
      was used as the glycosyl donor, and alpha-glycoconjugation was controlled by
      using the 7,8-di-O-picoloyl moiety in CH2Cl2. The methodology was successfully
      applied to the total synthesis of ganglioside Hp-s1 possessing neuritogenic
      activity.

PMID- 28753309
TI  - Anti-inflammatory Meroterpenoids from Baeckea frutescens.
AB  - Frutescones H-R (1-11), new sesqui- or monoterpene-based meroterpenoids, were
      isolated from the aerial parts of Baeckea frutescens. Their structures and
      absolute configurations were established by means of spectroscopic analyses
      (HRESIMS, 1D and 2D NMR, and ECD), as well as single-crystal X-ray
      crystallography of 1, (-)-7, and 9. The anti-inflammatory activities of all
      isolates were evaluated by measuring their inhibitory effects on NO production in
      LPS-stimulated RAW 264.7 macrophages, and the structure-activity relationships of
      1-11 are also discussed. Compound 8 exhibited anti-inflammatory activity with an
      IC50 value of 0.36 MUM, which might be related to the regulation of the NF-kappaB
      signaling pathway via the suppression of p65 nuclear translocation and the
      consequent decrease of IL-6 and TNF-alpha.

PMID- 28753310
TI  - Scanning Tunneling Microscopy Study of the Structure and Interaction between
      Carbon Monoxide and Hydrogen on the Ru(0001) Surface.
AB  - We use scanning tunneling microscopy (STM) to investigate the spatial arrangement
      of carbon monoxide (CO) and hydrogen (H) coadsorbed on a model catalyst surface,
      Ru(0001). We find that at cryogenic temperatures, CO forms small triangular
      islands of up to 21 molecules with hydrogen segregated outside of the islands.
      Furthermore, whereas for small island sizes (3-6 CO molecules) the molecules
      adsorb at hcp sites, a registry shift toward top sites occurs for larger islands
      (10-21 CO molecules). To characterize the CO structures better and to help
      interpret the data, we carried out density functional theory (DFT) calculations
      of the structure and simulations of the STM images, which reveal a delicate
      interplay between the repulsions of the different species.

PMID- 28753311
TI  - Isonicotinate Ester Catalyzed Decarboxylative Borylation of (Hetero)Aryl and
      Alkenyl Carboxylic Acids through N-Hydroxyphthalimide Esters.
AB  - Decarboxylative borylation of aryl and alkenyl carboxylic acids with
      bis(pinacolato)diboron was achieved through N-hydroxyphthalimide esters using
      tert-butyl isonicotinate as a catalyst under base-free conditions. A variety of
      aryl carboxylic acids possessing different functional groups and electronic
      properties can be smoothly converted to aryl boronate esters, including those
      that are difficult to decarboxylate under transition-metal catalysis, offering a
      new method enabling use of carboxylic acid as building blocks in organic
      synthesis. Mechanistic analysis suggests the reaction proceeds through coupling
      of a transient aryl radical generated by radical decarboxylation with a pyridine
      stabilized persistent boryl radical. Activation of redox active esters may
      proceed via an intramolecular single-electron-transfer (SET) process through a
      pyridine-diboron-phthalimide adduct and accounts for the base-free reaction
      conditions.

PMID- 28753312
TI  - Disorder from the Bulk Ionic Liquid in Electric Double Layer Transistors.
AB  - Ionic liquid gating has a number of advantages over solid-state gating,
      especially for flexible or transparent devices and for applications requiring
      high carrier densities. However, the large number of charged ions near the
      channel inevitably results in Coulomb scattering, which limits the carrier
      mobility in otherwise clean systems. We develop a model for this Coulomb
      scattering. We validate our model experimentally using ionic liquid gating of
      graphene across varying thicknesses of hexagonal boron nitride, demonstrating
      that disorder in the bulk ionic liquid often dominates the scattering.

PMID- 28753313
TI  - Neuroactive Steroids. 2. 3alpha-Hydroxy-3beta-methyl-21-(4-cyano-1H-pyrazol-1'
      yl)-19-nor-5beta-pregnan-20-one (SAGE-217): A Clinical Next Generation
      Neuroactive Steroid Positive Allosteric Modulator of the (gamma-Aminobutyric
      Acid)A Receptor.
AB  - Certain classes of neuroactive steroids (NASs) are positive allosteric modulators
      (PAM) of synaptic and extrasynaptic GABAA receptors. Herein, we report new SAR
      insights in a series of 5beta-nor-19-pregnan-20-one analogues bearing substituted
      pyrazoles and triazoles at C-21, culminating in the discovery of 3alpha-hydroxy
      3beta-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5beta-pregnan-20-one (SAGE-217,
      3), a potent GABAA receptor modulator at both synaptic and extrasynaptic receptor
      subtypes, with excellent oral DMPK properties. Compound 3 has completed a phase 1
      single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial and
      is currently being studied in parallel phase 2 clinical trials for the treatment
      of postpartum depression (PPD), major depressive disorder (MDD), and essential
      tremor (ET).

PMID- 28753314
TI  - Nanoridge Formation and Dynamics of Stratification in Micellar Freestanding
      Films.
AB  - Controlling and predicting the stability and lifetime of freestanding films,
      including foam and emulsion films, is crucial for many industrial and biological
      applications. Freestanding films (thickness <100 nm), stabilized by surfactants
      above the critical micelle concentration, exhibit stratification or stepwise
      thinning. Stratification proceeds by formation of thinner domains that grow at
      the expense of surrounding films. In this Article, we address several
      longstanding challenges related to the experimental characterization and
      theoretical description of thickness variations, forces, fluxes and flows
      underlying stratification. We show that nanoridges form and grow at the moving
      front around expanding domains, and we visualize their shape evolution using
      Interferometry Digital Imaging Optical Microscopy (IDIOM) protocols with an
      unprecedented spatiotemporal resolution (thickness <10 nm, time <1 ms). We
      develop a theoretical model for drainage via stratification under the influence
      of supramolecular oscillatory surface forces arising from the confinement-induced
      layering of micelles, and we show that the nanoridge growth and domain expansion
      dynamics can be modeled quantitatively.

PMID- 28753315
TI  - Hierarchical Self-Assembly of Histidine-Functionalized Peptide Amphiphiles into
      Supramolecular Chiral Nanostructures.
AB  - Controlling the hierarchical organization of self-assembling peptide amphiphiles
      into supramolecular nanostructures opens up the possibility of developing
      biocompatible functional supramolecular materials for various applications. In
      this study, we show that the hierarchical self-assembly of histidine- (His-)
      functionalized PAs containing d- or l-amino acids can be controlled by both
      solution pH and molecular chirality of the building blocks. An increase in
      solution pH resulted in the structural transition of the His-functionalized
      chiral PA assemblies from nanosheets to completely closed nanotubes through an
      enhanced hydrogen-bonding capacity and pi-pi stacking of imidazole ring. The
      effects of the stereochemistry and amino acid sequence of the PA backbone on the
      supramolecular organization were also analyzed by CD, TEM, SAXS, and molecular
      dynamics simulations. In addition, an investigation of chiral mixtures revealed
      the differences between the hydrogen-bonding capacities and noncovalent
      interactions of PAs with d- and l-amino acids.

PMID- 28753316
TI  - Inhibitory Potential of Red Cabbage against Digestive Enzymes Linked to Obesity
      and Type 2 Diabetes.
AB  - Assays of the inhibitory potential against enzymes involved in carbohydrate and
      lipid digestion (alpha-amylase, alpha-glucosidase, and lipase) as well as the
      total contents of phenolics and anthocyanins, anthocyanin profile, and
      antioxidant capacity revealed significant differences (p < 0.05) between five
      varieties of red cabbage. Among the varieties, the highest inhibitory activity
      against alpha-glucosidase (IC50 = 3.87 +/- 0.12 mg dry weight (DW) of cabbage/mL)
      and lipase (IC50 = 1.57 +/- 0.06 mg DW/mL) was exhibited by the Koda variety,
      which showed the highest antioxidant capacity in ABTS (Trolox equivalent
      antioxidant capacity (TEAC) = 141 +/- 4.71 MUmol/g DW) and ferric-reducing
      antioxidant power (TEAC = 125 +/- 1.94 MUmol/g DW) assays and had the highest
      total phenolics level (19.6 +/- 0.48 mg/g DW). The highest total anthocyanin
      content (12.0 +/- 0.16 mg/g DW) and inhibitory activity against alpha-amylase
      (IC50 = 69.0 +/- 3.65 mg DW of cabbage/mL) was shown by the Kissendrup variety.
      The anthocyanin profiles of these two varieties were characterized by the highest
      percentages of diacylated cyanidin derivatives. There was no correlation between
      the contents of phenolic compounds and lipase inhibitory activity, but inhibition
      of alpha-amylase was correlated with concentrations of monoacylated and
      diacylated anthocyanins, while inhibition of alpha-glucosidase increased with
      total phenolics and diacylated anthocyanins levels.

PMID- 28753317
TI  - Natural Particulates Inspired Specific-Targeted Codelivery of siRNA and
      Paclitaxel for Collaborative Antitumor Therapy.
AB  - The effective combination of drugs promoting antiangiogenesis and apoptosis
      effects has proven to be a promising collaborative tumor antidote; and the
      codelivery of small interfering RNA (siRNA) and chemotherapy agents within one
      efficient vehicle has gained more attention over single regimen administration.
      Herein, vascular endothelial growth factor specific siRNA (siVEGF) and paclitaxel
      (PTX) were introduced as therapeutic companions and coencapsulated into naturally
      mimic high-density lipoproteins (rHDL/siVEGF-PTX), so that various mechanisms of
      treatment can occur simultaneously. The terminal nanoparticles share capacity of
      specific-targeting to tumor cells overexpressed scavenger receptor class B type I
      (SR-BI) and deliver siVEGF and PTX into cytoplasm by a nonendocytosis mechanism.
      By exchanging HDL core lipids with hydrophobic therapeutics, rHDL/siVEGF-PTX
      possessed particle size of ~160 nm, surface potential of ~-20 mV, and desirable
      long-term storage stability. In vitro results confirmed that the parallel
      activity of siVEGF and PTX displayed enhanced anticancer efficacy. The half
      maximal inhibitory concentration (IC50) of rHDL/siVEGF-PTX toward human breast
      cancer MCF-7 cell is 0.26 MUg/mL (PTX concentration), which presents a 14.96-fold
      increase in cytotoxicity by taking Taxol as comparison. Moreover, in vivo results
      further demonstrated that rHDL/siVEGF-PTX performed enhanced tumor growth
      inhibition via natural targeting pathway, accompanied by remarkable inhibition of
      neovascularization in situ caused by siVEGF silencing in down-regulation of VEGF
      proteins. On the premise of effective drug codelivery, rHDL/siVEGF-PTX
      demonstrated high tumor targeting for collaborative antitumor efficacy without
      side effects after systemic administration, and this bioinspired strategy could
      open an avenue for exploration of combined anticancer therapy.

PMID- 28753318
TI  - Transient Melting and Recrystallization of Semiconductor Nanocrystals Under
      Multiple Electron-Hole Pair Excitation.
AB  - Ultrafast optical pump, X-ray diffraction probe experiments were performed on
      CdSe nanocrystal (NC) colloidal dispersions as functions of particle size,
      polytype, and pump fluence. Bragg peak shifts related to heating and peak
      amplitude reduction associated with lattice disordering are observed. For smaller
      NCs, melting initiates upon absorption of as few as ~15 electron-hole pair
      excitations per NC on average (0.89 excitations/nm3 for a 1.5 nm radius) with
      roughly the same excitation density inducing melting for all examined NCs.
      Diffraction intensity recovery kinetics, attributable to recrystallization, occur
      over hundreds of picoseconds with slower recoveries for larger particles.
      Zincblende and wurtzite NCs revert to initial structures following intense
      photoexcitation suggesting melting occurs primarily at the surface, as supported
      by simulations. Electronic structure calculations relate significant band gap
      narrowing with decreased crystallinity. These findings reflect the need to
      consider the physical stability of nanomaterials and related electronic impacts
      in high intensity excitation applications such as lasing and solid-state
      lighting.

PMID- 28753319
TI  - Imaging of Interlayer Coupling in van der Waals Heterostructures Using a Bright
      Field Optical Microscope.
AB  - Vertically stacked atomic layers from different layered crystals can be held
      together by van der Waals forces, which can be used for building novel
      heterostructures, offering a platform for developing a new generation of
      atomically thin, transparent, and flexible devices. The performance of these
      devices is critically dependent on the layer thickness and the interlayer
      electronic coupling, influencing the hybridization of the electronic states as
      well as charge and energy transfer between the layers. The electronic coupling is
      affected by the relative orientation of the layers as well as by the cleanliness
      of their interfaces. Here, we demonstrate an efficient method for monitoring
      interlayer coupling in heterostructures made from transition metal
      dichalcogenides using photoluminescence imaging in a bright-field optical
      microscope. The color and brightness in such images are used here to identify
      mono- and few-layer crystals and to track changes in the interlayer coupling and
      the emergence of interlayer excitons after thermal annealing in heterobilayers
      composed of mechanically exfoliated flakes and as a function of the twist angle
      in atomic layers grown by chemical vapor deposition. Material and crystal
      thickness sensitivity of the presented imaging technique makes it a powerful tool
      for characterization of van der Waals heterostructures assembled by a wide
      variety of methods, using combinations of materials obtained through mechanical
      or chemical exfoliation and crystal growth.

PMID- 28753320
TI  - Group Contribution Approach To Predict the Refractive Index of Pure Organic
      Components in Ambient Organic Aerosol.
AB  - We introduce and assess a group contribution scheme by which the refractive index
      (RI) (lambda = 589 nm) of nonabsorbing components common to secondary organic
      aerosols can be predicted from the molecular formula and chemical functionality.
      The group contribution method is based on representative values of ratios of the
      molecular polarizability and molar volume of different functional groups derived
      from data for a training set of 234 compounds. The training set consists of 106
      nonaromatic compounds common to atmospheric aerosols, 64 aromatic compounds, and
      64 compounds containing halogens; a separate group contribution model is provided
      for each of these three classes of compound. The resulting predictive model
      reproduces the RIs of compounds in the training set with mean errors of +/-0.58,
      +/-0.36, and +/-0.30% for the nonaromatic, aromatic, and halogen-containing
      compounds, respectively. We then evaluate predictions from the group contribution
      model for compounds with no previously reported RI, comparing values with
      predictions from previous treatments and with measurements from single aerosol
      particle experiments. We illustrate how such comparisons can be used to further
      refine the predictive model. We suggest that the accuracy of this model is
      already sufficient to better constrain the optical properties of organic aerosol
      of known composition.

PMID- 28753321
TI  - Stable in Bulk and Aggregating at the Interface: Comparing Core-Shell
      Nanoparticles in Suspension and at Fluid Interfaces.
AB  - Colloidal particles are extensively used to assemble materials from bulk
      suspensions or after adsorption and confinement at fluid interfaces (e.g., oil
      water interfaces). Interestingly, and often underestimated, optimizing
      interactions for bulk assembly may not lead to the same behavior at fluid
      interfaces. In this work, we compare model composite nanoparticles with a silica
      core coated with a poly-N-isopropylacrylamide hydrogel shell in bulk aqueous
      suspensions and after adsorption at an oil-water interface. Bulk properties are
      analyzed by confocal differential dynamic microscopy, a recently developed
      technique that allows one to simultaneously obtain structural and dynamical
      information up to high volume fractions. The results demonstrate excellent
      colloidal stability and the absence of aggregation in all cases. The behavior at
      the interface, investigated by a range of complementary approaches, is instead
      different. The same hydrogel shells that stabilize the particles in the bulk
      deform at the interface and induce attractive capillary interactions that lead to
      aggregation even at very low area fractions (surface coverage). Upon further
      compression of a particle-laden interface, a structural transition is observed
      where closely packed particle aggregates form. These findings emphasize the
      manifestation of different, and possibly unexpected, responses for sterically
      stabilized nanoparticles in the bulk and upon interfacial confinement.

PMID- 28753322
TI  - Development of a Fiber-Optics Microspatially Offset Raman Spectroscopy Sensor for
      Probing Layered Materials.
AB  - Microspatially offset Raman spectroscopy (micro-SORS) has been proposed as a
      valuable approach to sample molecular information from layers that are covered by
      a turbid (nontransparent) layer. However, when large magnifications are involved,
      the approach is not straightforward, as spatial constraints exist to position the
      laser beam and the objective lens with the external beam delivery or, with
      internal beam delivery, the maximum spatial offset achievable is restricted. To
      overcome these limitations, we propose here a prototype of a new micro-SORS
      sensor, which uses bare glass fibers to transfer the laser radiation to the
      sample and to collect the Raman signal from a spatially offset zone to the Raman
      spectrometer. The concept also renders itself amenable to remote delivery and to
      the miniaturization of the probe head which could be beneficial for special
      applications, e.g., where access to sample areas is restricted. The basic
      applicability of this approach was demonstrated by studying several layered
      structure systems. Apart from proving the feasibility of the technique, also,
      practical aspects of the use of the prototype sensor are discussed.

PMID- 28753323
TI  - Two-Dimensional J_{eff}=1/2 Antiferromagnetic Insulator Unraveled from Interlayer
      Exchange Coupling in Artificial Perovskite Iridate Superlattices.
AB  - We report an experimental investigation of the two-dimensional J_{eff}=1/2
      antiferromagnetic Mott insulator by varying the interlayer exchange coupling in
      [(SrIrO_{3})_{1}, (SrTiO_{3})_{m}] (m=1, 2 and 3) superlattices. Although all
      samples exhibited an insulating ground state with long-range magnetic order,
      temperature-dependent resistivity measurements showed a stronger insulating
      behavior in the m=2 and m=3 samples than the m=1 sample which displayed a clear
      kink at the magnetic transition. This difference indicates that the blocking
      effect of the excessive SrTiO_{3} layer enhances the effective electron-electron
      correlation and strengthens the Mott phase. The significant reduction of the Neel
      temperature from 150 K for m=1 to 40 K for m=2 demonstrates that the long-range
      order stability in the former is boosted by a substantial interlayer exchange
      coupling. Resonant x-ray magnetic scattering revealed that the interlayer
      exchange coupling has a switchable sign, depending on the SrTiO_{3} layer number
      m, for maintaining canting-induced weak ferromagnetism. The nearly unaltered
      transition temperature between the m=2 and the m=3 demonstrated that we have
      realized a two-dimensional antiferromagnet at finite temperatures with
      diminishing interlayer exchange coupling.

PMID- 28753324
TI  - Dzyaloshinskii-Moriya Interaction across an Antiferromagnet-Ferromagnet
      Interface.
AB  - The antiferromagnet- (AFM-)ferromagnet (FM) interfaces are of central importance
      in recently developed pure electric or ultrafast control of FM spins, where the
      underlying mechanisms remain unresolved. Here we report the direct observation of
      an Dzyaloshinskii-Moriya interaction (DMI) across the AFM-FM interface of
      IrMn/CoFeB thin films. The interfacial DMI is quantitatively measured from the
      asymmetric spin-wave dispersion in the FM layer using Brillouin light scattering.
      The DMI strength is enhanced by a factor of 7 with increasing IrMn layer
      thickness in the range of 1-7.5 nm. Our findings provide deeper insight into the
      coupling at the AFM-FM interface and may stimulate new device concepts utilizing
      chiral spin textures such as magnetic Skyrmions in AFM-FM heterostructures.

PMID- 28753325
TI  - Shape Universality Classes in the Random Sequential Adsorption of Nonspherical
      Particles.
AB  - Random sequential adsorption (RSA) of particles of a particular shape is used in
      a large variety of contexts to model particle aggregation and jamming. A key
      feature of these models is the observed algebraic time dependence of the
      asymptotic jamming coverage ~t^{-nu} as t->infinity. However, the exact value of
      the exponent nu is not known apart from the simplest case of the RSA of
      monodisperse spheres adsorbed on a line (Renyi's seminal "car parking problem"),
      where nu=1 can be derived analytically. Empirical simulation studies have
      conjectured on a case-by-case basis that for general nonspherical particles,
      nu=1/(d+d[over ~]), where d denotes the dimension of the domain, and d[over ~]
      the number of orientational degrees of freedom of a particle. Here, we solve this
      long-standing problem analytically for the d=1 case-the "Paris car parking
      problem." We prove, in particular, that the scaling exponent depends on the
      particle shape, contrary to the original conjecture and, remarkably, falls into
      two universality classes: (i) nu=1/(1+d[over ~]/2) for shapes with a smooth
      contact distance, e.g., ellipsoids, and (ii) nu=1/(1+d[over ~]) for shapes with a
      singular contact distance, e.g., spherocylinders and polyhedra. The exact
      solution explains, in particular, why many empirically observed scalings fall in
      between these two limits.

PMID- 28753326
TI  - First-Principles Vibrational Electron Energy Loss Spectroscopy of beta-Guanine.
AB  - A general approach to model vibrational electron energy loss spectra obtained
      using an electron beam positioned away from the specimen is presented. The energy
      loss probability of the fast electron is evaluated using first-principles quantum
      mechanical calculations (density functional theory) of the dielectric response of
      the specimen. The validity of the method is assessed using recently measured
      anhydrous beta-guanine, an important molecular solid used by animals to produce
      structural colors. The good agreement between theory and experiments lays the
      basis for a quantitative interpretation of this spectroscopy in complex systems.

PMID- 28753327
TI  - Landau Level Mixing and the Ground State of the nu=5/2 Quantum Hall Effect.
AB  - Inter-Landau-level transitions break particle hole symmetry and will choose
      either the Pfaffian or the anti-Pfaffian state as the absolute ground state at
      5/2 filling of the fractional quantum Hall effect. An approach based on
      truncating the Hilbert space has favored the anti-Pfaffian. A second approach
      based on an effective Hamiltonian produced the Pfaffian. In this Letter,
      perturbation theory is applied to finite sizes without bias to any specific
      pseudopotential component. This method also singles out the anti-Pfaffian. A
      critical piece of the effective Hamiltonian, which was absent in previous
      studies, reverts the ground state at 5/2 to the anti-Pfaffian.

PMID- 28753328
TI  - Edge Fracture in Complex Fluids.
AB  - We study theoretically the edge fracture instability in sheared complex fluids,
      by means of linear stability analysis and direct nonlinear simulations. We derive
      an exact analytical expression for the onset of edge fracture in terms of the
      shear-rate derivative of the fluid's second normal stress difference, the shear
      rate derivative of the shear stress, the jump in shear stress across the
      interface between the fluid and the outside medium (usually air), the surface
      tension of that interface, and the rheometer gap size. We provide a full
      mechanistic understanding of the edge fracture instability, carefully validated
      against our simulations. These findings, which are robust with respect to choice
      of rheological constitutive model, also suggest a possible route to mitigating
      edge fracture, potentially allowing experimentalists to achieve and accurately
      measure flows stronger than hitherto possible.

PMID- 28753329
TI  - Barnett Replies.

PMID- 28753330
TI  - Experimental Verification of the Very Strong Coupling Regime in a GaAs Quantum
      Well Microcavity.
AB  - The dipole coupling strength g between cavity photons and quantum well excitons
      determines the regime of light matter coupling in quantum well microcavities. In
      the strong coupling regime, a reversible energy transfer between exciton and
      cavity photon takes place, which leads to the formation of hybrid polaritonic
      resonances. If the coupling is further increased, a hybridization of different
      single exciton states emerges, which is referred to as the very strong coupling
      regime. In semiconductor quantum wells such a regime is predicted to manifest as
      a photon-mediated electron-hole coupling leading to different excitonic wave
      functions for the two polaritonic branches when the ratio of the coupling
      strength to exciton binding energy g/E_{B} approaches unity. Here, we verify
      experimentally the existence of this regime in magneto-optical measurements on a
      microcavity characterized by g/E_{B}~0.64, showing that the average electron-hole
      separation of the upper polariton is significantly increased compared to the bare
      quantum well exciton Bohr radius. This yields a diamagnetic shift around 0
      detuning that exceeds the shift of the lower polariton by 1 order of magnitude
      and the bare quantum well exciton diamagnetic shift by a factor of 2. The lower
      polariton exhibits a diamagnetic shift smaller than expected from the coupling of
      a rigid exciton to the cavity mode, which suggests more tightly bound electron
      hole pairs than in the bare quantum well.

PMID- 28753331
TI  - Bright-Exciton Fine-Structure Splittings in Single Perovskite Nanocrystals.
AB  - Here we show that, in single perovskite CsPbI_{3} nanocrystals synthesized from a
      colloidal approach, a bright-exciton fine-structure splitting as large as
      hundreds of MUeV can be resolved with two orthogonally and linearly polarized
      photoluminescence peaks. This doublet could switch to a single peak when a single
      CsPbI_{3} nanocrystal is photocharged to eliminate the electron-hole exchange
      interaction. The above findings have prepared an efficient platform suitable for
      probing exciton and spin dynamics of semiconductor nanostructures at the visible
      wavelength range, from which a variety of practical applications such as in
      entangled photon-pair source and quantum information processing can be
      envisioned.

PMID- 28753332
TI  - Erratum: Upper Limits on the Stochastic Gravitational-Wave Background from
      Advanced LIGO's First Observing Run [Phys. Rev. Lett. 118, 121101 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.121101.

PMID- 28753333
TI  - Experimental Evidence for Quantum Tunneling Time.
AB  - The first hundred attoseconds of the electron dynamics during strong field
      tunneling ionization are investigated. We quantify theoretically how the
      electron's classical trajectories in the continuum emerge from the tunneling
      process and test the results with those achieved in parallel from attoclock
      measurements. An especially high sensitivity on the tunneling barrier is
      accomplished here by comparing the momentum distributions of two atomic species
      of slightly deviating atomic potentials (argon and krypton) being ionized under
      absolutely identical conditions with near-infrared laser pulses (1300 nm). The
      agreement between experiment and theory provides clear evidence for a nonzero
      tunneling time delay and a nonvanishing longitudinal momentum of the electron at
      the "tunnel exit."

PMID- 28753334
TI  - No-Hypersignaling Principle.
AB  - A paramount topic in quantum foundations, rooted in the study of the Einstein
      Podolsky-Rosen (EPR) paradox and Bell inequalities, is that of characterizing
      quantum theory in terms of the spacelike correlations it allows. Here, we show
      that to focus only on spacelike correlations is not enough: we explicitly
      construct a toy model theory that, while not contradicting classical and quantum
      theories at the level of spacelike correlations, still displays an anomalous
      behavior in its timelike correlations. We call this anomaly, quantified in terms
      of a specific communication game, the "hypersignaling" phenomena. We hence
      conclude that the "principle of quantumness," if it exists, cannot be found in
      spacelike correlations alone: nontrivial constraints need to be imposed also on
      timelike correlations, in order to exclude hypersignaling theories.

PMID- 28753335
TI  - Generation and Evolution of High-Mach-Number Laser-Driven Magnetized
      Collisionless Shocks in the Laboratory.
AB  - We present the first laboratory generation of high-Mach-number magnetized
      collisionless shocks created through the interaction of an expanding laser-driven
      plasma with a magnetized ambient plasma. Time-resolved, two-dimensional imaging
      of plasma density and magnetic fields shows the formation and evolution of a
      supercritical shock propagating at magnetosonic Mach number M_{ms}~12. Particle
      in-cell simulations constrained by experimental data further detail the shock
      formation and separate dynamics of the multi-ion-species ambient plasma. The
      results show that the shocks form on time scales as fast as one gyroperiod, aided
      by the efficient coupling of energy, and the generation of a magnetic barrier
      between the piston and ambient ions. The development of this experimental
      platform complements present remote sensing and spacecraft observations, and
      opens the way for controlled laboratory investigations of high-Mach number
      collisionless shocks, including the mechanisms and efficiency of particle
      acceleration.

PMID- 28753336
TI  - Beam-Recoil Polarization Measurement of pi^{0} Electroproduction on the Proton in
      the Region of the Roper Resonance.
AB  - The helicity-dependent recoil proton polarizations P_{x}^{'} and P_{z}^{'} as
      well as the helicity-independent component P_{y} have been measured in the
      p(e[over ->],e^{'}p[over ->])pi^{0} reaction at four-momentum transfer Q^{2}?0.1 
      GeV^{2}, center-of-mass proton emission angle theta_{p}^{*}?90 degrees , and
      invariant mass W?1440  MeV. This first precise measurement of double-polarization
      observables in the energy domain of the Roper resonance P_{11}(1440) by
      exploiting recoil polarimetry has allowed for the extraction of its scalar
      electroexcitation amplitude at an unprecedentedly low value of Q^{2},
      establishing a powerful instrument for probing the interplay of quark and meson
      degrees of freedom in the nucleon.

PMID- 28753337
TI  - Experimental Evidence for a Structural-Dynamical Transition in Trajectory Space.
AB  - Among the key insights into the glass transition has been the identification of a
      nonequilibrium phase transition in trajectory space which reveals phase
      coexistence between the normal supercooled liquid (active phase) and a glassy
      state (inactive phase). Here, we present evidence that such a transition occurs
      in experiments. In colloidal hard spheres, we find a non-Gaussian distribution of
      trajectories leaning towards those rich in locally favored structures (LFSs),
      associated with the emergence of slow dynamics. This we interpret as evidence for
      a nonequilibrium transition to an inactive LFS-rich phase. Reweighting
      trajectories reveals a first-order phase transition in trajectory space between a
      normal liquid and a LFS-rich phase. We also find evidence for a purely dynamical
      transition in trajectory space.

PMID- 28753338
TI  - Multipole Superconductivity in Nonsymmorphic Sr_{2}IrO_{4}.
AB  - Discoveries of marked similarities to high-T_{c} cuprate superconductors point to
      the realization of superconductivity in the doped J_{eff}=1/2 Mott insulator
      Sr_{2}IrO_{4}. Contrary to the mother compound of cuprate superconductors,
      several stacking patterns of in-plane canted antiferromagnetic moments have been
      reported, which are distinguished by the ferromagnetic components as -++-, ++++,
      and -+-+. In this paper, we clarify unconventional features of the
      superconductivity coexisting with -++- and -+-+ structures. Combining the group
      theoretical analysis and numerical calculations for an effective J_{eff}=1/2
      model, we show unusual superconducting gap structures in the -++- state protected
      by nonsymmorphic magnetic space group symmetry. Furthermore, our calculation
      shows that the Fulde-Ferrell-Larkin-Ovchinnikov superconductivity is inevitably
      stabilized in the -+-+ state since the odd-parity magnetic -+-+ order makes the
      band structure asymmetric by cooperating with spin-orbit coupling. These unusual
      superconducting properties are signatures of magnetic multipole order in
      nonsymmorphic crystal.

PMID- 28753339
TI  - Glass Transition Temperature and Density Scaling in Cumene at Very High Pressure.
AB  - We present a new method that allows direct measurements of the glass transition
      temperature T_{g} at pressures up to 4.55 GPa in the glass-forming liquid cumene
      (isopropylbenzene). This new method uses a diamond anvil cell and can measure
      T_{g} at pressures of 10 GPa or greater. Measuring T_{g} at the glass->liquid
      transition involves monitoring the disappearance of pressure gradients initially
      present in the glass, but also takes advantage of the large increase in the
      volume expansion coefficient alpha_{p} at T_{g} as the supercooled or
      superpressed liquid is entered. Accurate T_{g}(P) values in cumene allow us to
      show that density scaling holds along this isochronous line up to pressures much
      higher than any previous study, corresponding to a density increase of 29%. Our
      results for cumene over this huge compression range yield rho^{gamma}/T=C, where
      C is a constant and where gamma=4.77+/-0.02 for this nonassociated glass-forming
      system. Finally, high-pressure cumene viscosity data from the literature taken at
      much lower pressures and at several different temperatures, corresponding to a
      large dynamic range of nearly 13 orders of magnitude, are shown to superimpose on
      a plot of eta vs rho^{gamma}/T for the same value of gamma.

PMID- 28753340
TI  - Entanglement Entropy of Eigenstates of Quadratic Fermionic Hamiltonians.
AB  - In a seminal paper [D. N. Page, Phys. Rev. Lett. 71, 1291 (1993)PRLTAO0031
      900710.1103/PhysRevLett.71.1291], Page proved that the average entanglement
      entropy of subsystems of random pure states is S_{ave}?lnD_{A}-(1/2)D_{A}^{2}/D
      for 1?D_{A}<=sqrt[D], where D_{A} and D are the Hilbert space dimensions of the
      subsystem and the system, respectively. Hence, typical pure states are (nearly)
      maximally entangled. We develop tools to compute the average entanglement entropy
      ?S? of all eigenstates of quadratic fermionic Hamiltonians. In particular, we
      derive exact bounds for the most general translationally invariant models lnD_{A}
      (lnD_{A})^{2}/lnD<=?S?<=lnD_{A}-[1/(2ln2)](lnD_{A})^{2}/lnD. Consequently, we
      prove that (i) if the subsystem size is a finite fraction of the system size,
      then ?S?<lnD_{A} in the thermodynamic limit; i.e., the average over eigenstates
      of the Hamiltonian departs from the result for typical pure states, and (ii) in
      the limit in which the subsystem size is a vanishing fraction of the system size,
      the average entanglement entropy is maximal; i.e., typical eigenstates of such
      Hamiltonians exhibit eigenstate thermalization.

PMID- 28753341
TI  - Observation of Excited Quadrupole-Bound States in Cold Anions.
AB  - We report the first observation of an excited quadrupole-bound state (QBS) in an
      anion. High-resolution photoelectron imaging of cryogenically cooled 4
      cyanophenoxide (4CP^{-}) anions yields an electron detachment threshold of 24 927
      cm^{-1}. The photodetachment spectrum reveals a resonant transition 20  cm^{-1}
      below the detachment threshold, which is attributed to an excited QBS of 4CP^{-}
      because neutral 4CP has a large quadrupole moment with a negligible dipole
      moment. The QBS is confirmed by observation of seventeen above-threshold
      resonances due to autodetachment from vibrational levels of the QBS.

PMID- 28753342
TI  - Three-Dimensional Electronic Structure of the Type-II Weyl Semimetal WTe_{2}.
AB  - By combining bulk sensitive soft-x-ray angular-resolved photoemission
      spectroscopy and first-principles calculations we explored the bulk electron
      states of WTe_{2}, a candidate type-II Weyl semimetal featuring a large
      nonsaturating magnetoresistance. Despite the layered geometry suggesting a two
      dimensional electronic structure, we directly observe a three-dimensional
      electronic dispersion. We report a band dispersion in the reciprocal direction
      perpendicular to the layers, implying that electrons can also travel coherently
      when crossing from one layer to the other. The measured Fermi surface is
      characterized by two well-separated electron and hole pockets at either side of
      the Gamma point, differently from previous more surface sensitive angle-resolved
      photoemission spectroscopy experiments that additionally found a pronounced
      quasiparticle weight at the zone center. Moreover, we observe a significant
      sensitivity of the bulk electronic structure of WTe_{2} around the Fermi level to
      electronic correlations and renormalizations due to self-energy effects,
      previously neglected in first-principles descriptions.

PMID- 28753343
TI  - Thermal Transport Signatures of Broken-Symmetry Phases in Graphene.
AB  - In the half filled zero-energy Landau level of bilayer graphene, competing phases
      with spontaneously broken symmetries and an intriguing quantum critical behavior
      have been predicted. Here we investigate signatures of these broken-symmetry
      phases in thermal transport measurements. To this end, we calculate the spectrum
      of spin and valley waves in the nu=0 quantum Hall state of bilayer graphene. The
      presence of Goldstone modes enables heat transport even at low temperatures,
      which can serve as compelling evidence for spontaneous symmetry breaking. By
      varying external electric and magnetic fields, it is possible to determine the
      nature of the symmetry breaking. Temperature-dependent measurements may yield
      additional information about gapped modes.

PMID- 28753344
TI  - Scaling Analysis of the Screening Length in Concentrated Electrolytes.
AB  - The interaction between charged objects in an electrolyte solution is a
      fundamental question in soft matter physics. It is well known that the
      electrostatic contribution to the interaction energy decays exponentially with
      object separation. Recent measurements reveal that, contrary to the conventional
      wisdom given by the classic Poisson-Boltzmann theory, the decay length increases
      with the ion concentration for concentrated electrolytes and can be an order of
      magnitude larger than the ion diameter in ionic liquids. We derive a simple
      scaling theory that explains this anomalous dependence of the decay length on the
      ion concentration. Our theory successfully collapses the decay lengths of a wide
      class of salts onto a single curve. A novel prediction of our theory is that the
      decay length increases linearly with the Bjerrum length, which we experimentally
      verify by surface force measurements. Moreover, we quantitatively relate the
      measured decay length to classic measurements of the activity coefficient in
      concentrated electrolytes, thus showing that the measured decay length is indeed
      a bulk property of the concentrated electrolyte as well as contributing a
      mechanistic insight into empirical activity coefficients.

PMID- 28753345
TI  - Interrogating Nanojunctions Using Ultraconfined Acoustoplasmonic Coupling.
AB  - Single nanoparticles are shown to develop a localized acoustic resonance, the
      bouncing mode, when placed on a substrate. If both substrate and nanoparticle are
      noble metals, plasmonic coupling of the nanoparticle to its image charges in the
      film induces tight light confinement in the nanogap. This yields ultrastrong
      "acoustoplasmonic" coupling with a figure of merit 7 orders of magnitude higher
      than conventional acousto-optic modulators. The plasmons thus act as a local
      vibrational probe of the contact geometry. A simple analytical mechanical model
      is found to describe the bouncing mode in terms of the nanoscale structure,
      allowing transient pump-probe spectroscopy to directly measure the contact area
      for individual nanoparticles.

PMID- 28753346
TI  - Reversible Bulk Oxidation of Ni Foil During Oscillatory Catalytic Oxidation of
      Propane: A Novel Type of Spatiotemporal Self-Organization.
AB  - A novel type of temporal and spatial self-organization in a heterogeneous
      catalytic reaction is described for the first time. Using in situ x-ray
      photoelectron spectroscopy, gas chromatography, and mass spectrometry, we show
      that, under certain conditions, self-sustained reaction-rate oscillations arise
      in the oxidation of propane over Ni foil because of reversible bulk oxidation of
      Ni to NiO, which can be observed even with the naked eye as chemical waves
      propagating over the catalyst surface.

PMID- 28753347
TI  - Understanding the Giant Enhancement of Exchange Interaction in Bi_{2}Se_{3}-EuS
      Heterostructures.
AB  - A recent experiment indicated that a ferromagnetic EuS film in contact with a
      topological insulator Bi_{2}Se_{3} might show a largely enhanced Curie
      temperature and perpendicular magnetic anisotropy [F. Katmis et al., Nature
      (London) 533, 513 (2016).NATUAS0028-083610.1038/nature17635]. Through systematic
      density functional calculations, we demonstrate that in addition to the factor
      that Bi_{2}Se_{3} has a strong spin orbit coupling, the topological surface
      states are crucial to make these unusual behaviors robust as they hybridize with
      EuS states and extend rather far into the magnetic layers. The magnetic moments
      of Eu atoms are nevertheless not much enhanced, unlike what was reported in the
      experiment. Our results and model analyses provide useful insights for how these
      quantities are linked, and pave a way for the control of properties of magnetic
      films via contact with topological insulators.

PMID- 28753348
TI  - Observation of Quasichanneling Oscillations.
AB  - We report on the first experimental observations of quasichanneling oscillations,
      recently seen in simulations and described theoretically. Although above-barrier
      particles penetrating a single crystal are generally seen as behaving almost as
      in an amorphous substance, distinct oscillation peaks nevertheless appear for
      particles in that category. The quasichanneling oscillations were observed at
      SLAC National Accelerator Laboratory by aiming 20.35 GeV positrons and electrons
      at a thin silicon crystal bent to a radius of R=0.15  m, exploiting the
      quasimosaic effect. For electrons, two relatively faint quasichanneling peaks
      were observed, while for positrons, seven quasichanneling peaks were clearly
      identified.

PMID- 28753349
TI  - Surfing on Protein Waves: Proteophoresis as a Mechanism for Bacterial Genome
      Partitioning.
AB  - Efficient bacterial chromosome segregation typically requires the coordinated
      action of a three-component machinery, fueled by adenosine triphosphate, called
      the partition complex. We present a phenomenological model accounting for the
      dynamic activity of this system that is also relevant for the physics of
      catalytic particles in active environments. The model is obtained by coupling
      simple linear reaction-diffusion equations with a proteophoresis, or "volumetric"
      chemophoresis, force field that arises from protein-protein interactions and
      provides a physically viable mechanism for complex translocation. This minimal
      description captures most known experimental observations: dynamic oscillations
      of complex components, complex separation, and subsequent symmetrical
      positioning. The predictions of our model are in phenomenological agreement with
      and provide substantial insight into recent experiments. From a nonlinear physics
      view point, this system explores the active separation of matter at micrometric
      scales with a dynamical instability between static positioning and traveling wave
      regimes triggered by the dynamical spontaneous breaking of rotational symmetry.

PMID- 28753350
TI  - gamma-ray Constraints on Decaying Dark Matter and Implications for IceCube.
AB  - Utilizing the Fermi measurement of the gamma-ray spectrum toward the Inner
      Galaxy, we derive some of the strongest constraints to date on the dark matter
      (DM) lifetime in the mass range from hundreds of MeV to above an EeV. Our profile
      likelihood-based analysis relies on 413 weeks of Fermi Pass 8 data from 200 MeV
      to 2 TeV, along with up-to-date models for diffuse gamma-ray emission within the
      Milky Way. We model Galactic and extragalactic DM decay and include contributions
      to the DM-induced gamma-ray flux resulting from both primary emission and inverse
      Compton scattering of primary electrons and positrons. For the extragalactic
      flux, we also calculate the spectrum associated with cascades of high-energy
      gamma rays scattering off of the cosmic background radiation. We argue that a
      decaying DM interpretation for the 10 TeV-1 PeV neutrino flux observed by IceCube
      is disfavored by our constraints. Our results also challenge a decaying DM
      explanation of the AMS-02 positron flux. We interpret the results in terms of
      individual final states and in the context of simplified scenarios such as a
      hidden-sector glueball model.

PMID- 28753351
TI  - Role of Correlations in the Collective Behavior of Microswimmer Suspensions.
AB  - In this Letter, we study the collective behavior of a large number of self
      propelled microswimmers immersed in a fluid. Using unprecedentedly large-scale
      lattice Boltzmann simulations, we reproduce the transition to bacterial
      turbulence. We show that, even well below the transition, swimmers move in a
      correlated fashion that cannot be described by a mean-field approach. We develop
      a novel kinetic theory that captures these correlations and is nonperturbative in
      the swimmer density. To provide an experimentally accessible measure of
      correlations, we calculate the diffusivity of passive tracers and reveal its
      nontrivial density dependence. The theory is in quantitative agreement with the
      lattice Boltzmann simulations and captures the asymmetry between pusher and
      puller swimmers below the transition to turbulence.

PMID- 28753352
TI  - Instability of Agyrotropic Electron Beams near the Electron Diffusion Region.
AB  - During a magnetopause crossing the Magnetospheric Multiscale spacecraft
      encountered an electron diffusion region (EDR) of asymmetric reconnection. The
      EDR is characterized by agyrotropic beam and crescent electron distributions
      perpendicular to the magnetic field. Intense upper-hybrid (UH) waves are found at
      the boundary between the EDR and magnetosheath inflow region. The UH waves are
      generated by the agyrotropic electron beams. The UH waves are sufficiently large
      to contribute to electron diffusion and scattering, and are a potential source of
      radio emission near the EDR. These results provide observational evidence of wave
      particle interactions at an EDR, and suggest that waves play an important role in
      determining the electron dynamics.

PMID- 28753353
TI  - Control of Coherently Coupled Exciton Polaritons in Monolayer Tungsten
      Disulphide.
AB  - Monolayer transition metal dichalcogenides (TMD) with confined 2D Wannier-Mott
      excitons are intriguing for the fundamental study of strong light-matter
      interactions and the exploration of exciton polaritons at high temperatures.
      However, the research of 2D exciton polaritons has been hindered because the
      polaritons in these atomically thin semiconductors discovered so far can hardly
      support strong nonlinear interactions and quantum coherence due to uncontrollable
      polariton dynamics and weakened coherent coupling. In this work, we demonstrate,
      for the first time, a precisely controlled hybrid composition with angular
      dependence and dispersion-correlated polariton emission by tuning the polariton
      dispersion in TMD over a broad temperature range of 110-230 K in a single cavity.
      This tamed polariton emission is achieved by the realization of robust coherent
      exciton-photon coupling in monolayer tungsten disulphide (WS_{2}) with large
      splitting-to-linewidth ratios (>3.3). The unprecedented ability to manipulate the
      dispersion and correlated properties of TMD exciton polaritons at will offers new
      possibilities to explore important quantum phenomena such as inversionless
      lasing, Bose-Einstein condensation, and superfluidity.

PMID- 28753354
TI  - Out-of-Time-Ordered Density Correlators in Luttinger Liquids.
AB  - Information scrambling and the butterfly effect in chaotic quantum systems can be
      diagnosed by out-of-time-ordered (OTO) commutators through an exponential growth
      and large late time value. We show that the latter feature shows up in a strongly
      correlated many-body system, a Luttinger liquid, whose density fluctuations we
      study at long and short wavelengths, both in equilibrium and after a quantum
      quench. We find rich behavior combining robustly universal and nonuniversal
      features. The OTO commutators display temperature- and initial-state-independent
      behavior and grow as t^{2} for short times. For the short-wavelength density
      operator, they reach a sizable value after the light cone only in an interacting
      Luttinger liquid, where the bare excitations break up into collective modes. This
      challenges the common interpretation of the OTO commutator in chaotic systems. We
      benchmark our findings numerically on an interacting spinless fermion model in 1D
      and find persistence of central features even in the nonintegrable case. As a
      nonuniversal feature, the short-time growth exhibits a distance-dependent power.

PMID- 28753355
TI  - Demonstrating an In Situ Topological Band Transition in Cylindrical Granular
      Chains.
AB  - We numerically investigate and experimentally demonstrate an in situ topological
      band transition in a highly tunable mechanical system made of cylindrical
      granular particles. This system allows us to tune its interparticle stiffness in
      a controllable way, simply by changing the contact angles between the cylinders.
      The spatial variation of particles' stiffness results in an in situ transition of
      the system's topology. This manifests as the emergence of a boundary mode in the
      finite system, which we observe experimentally via laser Doppler vibrometry. When
      two topologically different systems are placed adjacently, we analytically
      predict and computationally and experimentally demonstrate the existence of a
      finite-frequency topologically protected mode at their interface.

PMID- 28753356
TI  - Observation of Self-Cavitating Envelope Dispersive Shock Waves in Yttrium Iron
      Garnet Thin Films.
AB  - The formation and properties of envelope dispersive shock wave (DSW) excitations
      from repulsive nonlinear waves in a magnetic film are studied. Experiments
      involve the excitation of a spin wave step pulse in a low-loss magnetic
      Y_{3}Fe_{5}O_{12} thin film strip, in which the spin wave amplitude increases
      rapidly, realizing the canonical Riemann problem of shock theory. Under certain
      conditions, the envelope of the spin wave pulse evolves into a DSW that consists
      of an expanding train of nonlinear oscillations with amplitudes increasing from
      front to back, terminated by a black soliton. The onset of DSW self-cavitation,
      indicated by a point of zero power and a concomitant 180 degrees  phase jump, is
      observed for sufficiently large steps, indicative of the bidirectional dispersive
      hydrodynamic nature of the DSW. The experimental observations are interpreted
      with theory and simulations of the nonlinear Schrodinger equation.

PMID- 28753357
TI  - Dispersive Stiffness of Dzyaloshinskii Domain Walls.
AB  - It is well documented that subjecting perpendicular magnetic films that exhibit
      the interfacial Dzyaloshinskii-Moriya interaction to an in-plane magnetic field
      results in a domain wall (DW) energy sigma, which is highly anisotropic with
      respect to the orientation of the DW in the film plane Theta. We demonstrate that
      this anisotropy has a profound impact on the elastic response of the DW as
      characterized by the surface stiffness sigma[over
      ~](Theta)=sigma(Theta)+sigma^{''}(Theta) and evaluate its dependence on the
      length scale of deformation. The influence of stiffness on DW mobility in the
      creep regime is assessed, with analytic and numerical calculations showing trends
      in sigma[over ~] that better represent experimental measurements of domain wall
      velocity in magnetic thin films compared to sigma alone. Our treatment provides
      experimental support for theoretical models of the mobility of anisotropic
      elastic manifolds and makes progress toward a more complete understanding of
      magnetic domain wall creep.

PMID- 28753358
TI  - Topological Quantum Optics in Two-Dimensional Atomic Arrays.
AB  - We demonstrate that two-dimensional atomic emitter arrays with subwavelength
      spacing constitute topologically protected quantum optical systems where the
      photon propagation is robust against large imperfections while losses associated
      with free space emission are strongly suppressed. Breaking time-reversal symmetry
      with a magnetic field results in gapped photonic bands with nontrivial Chern
      numbers and topologically protected, long-lived edge states. Due to the inherent
      nonlinearity of constituent emitters, such systems provide a platform for
      exploring quantum optical analogs of interacting topological systems.

PMID- 28753359
TI  - Type-II Symmetry-Protected Topological Dirac Semimetals.
AB  - The recent proposal of the type-II Weyl semimetal state has attracted significant
      interest. In this Letter, we propose the concept of the three-dimensional type-II
      Dirac fermion and theoretically identify this new symmetry-protected topological
      state in the large family of transition-metal icosagenides, MA_{3} (M=V, Nb, Ta;
      A=Al, Ga, In). We show that the VAl_{3} family features a pair of strongly
      Lorentz-violating type-II Dirac nodes and that each Dirac node can be split into
      four type-II Weyl nodes with chiral charge +/-1 via symmetry breaking.
      Furthermore, we predict that the Landau level spectrum arising from the type-II
      Dirac fermions in VAl_{3} is distinct from that of known Dirac or Weyl
      semimetals. We also demonstrate a topological phase transition from a type-II
      Dirac semimetal to a quadratic Weyl semimetal or a topological crystalline
      insulator via crystalline distortions.

PMID- 28753360
TI  - Mode Selection in Compressible Active Flow Networks.
AB  - Coherent, large-scale dynamics in many nonequilibrium physical, biological, or
      information transport networks are driven by small-scale local energy input.
      Here, we introduce and explore an analytically tractable nonlinear model for
      compressible active flow networks. In contrast to thermally driven systems, we
      find that active friction selects discrete states with a limited number of
      oscillation modes activated at distinct fixed amplitudes. Using perturbation
      theory, we systematically predict the stationary states of noisy networks and
      find good agreement with a Bayesian state estimation based on a hidden Markov
      model applied to simulated time series data. Our results suggest that the
      macroscopic response of active network structures, from actomyosin force networks
      to cytoplasmic flows, can be dominated by a significantly reduced number of
      modes, in contrast to energy equipartition in thermal equilibrium. The model is
      also well suited to study topological sound modes and spectral band gaps in
      active matter.

PMID- 28753361
TI  - Comment on "Relativistic Electron Vortices".

PMID- 28753362
TI  - Microscopic Origin of Ideal Conductivity in Integrable Quantum Models.
AB  - Nonergodic dynamical systems display anomalous transport properties. Prominent
      examples are integrable quantum systems, whose exceptional properties are
      diverging dc conductivities. In this Letter, we explain the microscopic origin of
      ideal conductivity by resorting to the thermodynamic particle content of a
      system. Using group-theoretic arguments we rigorously resolve the long-standing
      controversy regarding the nature of spin and charge Drude weights in the absence
      of chemical potentials. In addition, by employing a hydrodynamic description, we
      devise an efficient computational method to calculate exact Drude weights from
      the stationary currents generated in an inhomogeneous quench from bipartitioned
      initial states. We exemplify the method on the anisotropic Heisenberg model at
      finite temperatures for the entire range of anisotropies, accessing regimes that
      are out of reach with other approaches. Quite remarkably, spin Drude weight and
      asymptotic spin current rates reveal a completely discontinuous (fractal)
      dependence on the anisotropy parameter.

PMID- 28753363
TI  - Detecting Patchy Reionization in the Cosmic Microwave Background.
AB  - Upcoming cosmic microwave background (CMB) experiments will measure temperature
      fluctuations on small angular scales with unprecedented precision. Small-scale
      CMB fluctuations are a mixture of late-time effects: gravitational lensing,
      Doppler shifting of CMB photons by moving electrons [the kinematic Sunyaev
      Zel'dovich (KSZ) effect], and residual foregrounds. We propose a new statistic
      which separates the KSZ signal from the others, and also allows the KSZ signal to
      be decomposed in redshift bins. The decomposition extends to high redshift and
      does not require external data sets such as galaxy surveys. In particular, the
      high-redshift signal from patchy reionization can be cleanly isolated, enabling
      future CMB experiments to make high-significance and qualitatively new
      measurements of the reionization era.

PMID- 28753364
TI  - Novel Cosmic-Ray Electron and Positron Constraints on MeV Dark Matter Particles.
AB  - MeV dark matter (DM) particles annihilating or decaying to electron-positron
      pairs cannot, in principle, be observed via local cosmic-ray (CR) measurements
      because of the shielding solar magnetic field. In this Letter, we take advantage
      of spacecraft Voyager 1's capacity for detecting interstellar CRs since it
      crossed the heliopause in 2012. This opens up a new avenue to probe DM in the sub
      GeV energy/mass range that we exploit here for the first time. From a complete
      description of the transport of electrons and positrons at low energy, we derive
      predictions for both the secondary astrophysical background and the pair
      production mechanisms relevant to DM annihilation or decay down to the MeV mass
      range. Interestingly, we show that reacceleration may push positrons up to
      energies larger than the DM particle mass. We combine the constraints from the
      Voyager and AMS-02 data to get novel limits covering a very extended DM particle
      mass range, from MeV to TeV. In the MeV mass range, our limits reach annihilation
      cross sections of order ?sigmav?~10^{-28}  cm^{3}/s. An interesting aspect is
      that these limits barely depend on the details of cosmic-ray propagation in the
      weak reacceleration case, a configuration which seems to be favored by the most
      recent B/C data. Though extracted from a completely different and new probe,
      these bounds have a strength similar to those obtained with the cosmic microwave
      background-they are even more stringent for p-wave annihilation.

PMID- 28753365
TI  - Nonclassical Photon Number Distribution in a Superconducting Cavity under a
      Squeezed Drive.
AB  - A superconducting qubit in the strong dispersive regime of circuit quantum
      electrodynamics is a powerful probe for microwave photons in a cavity mode. In
      this regime, a qubit excitation spectrum is split into multiple peaks, with each
      peak corresponding to an individual photon number in the cavity (discrete ac
      Stark shift). Here, we measure the qubit spectrum in a cavity that is driven
      continuously with a squeezed vacuum generated by a Josephson parametric
      amplifier. By fitting the obtained spectrum with a model which takes into account
      the finite qubit excitation power, we determine the photon number distribution,
      which reveals an even-odd photon number oscillation and quantitatively fulfills
      Klyshko's criterion for nonclassicality.

PMID- 28753366
TI  - Active versus Passive Hard Disks against a Membrane: Mechanical Pressure and
      Instability.
AB  - We experimentally study the mechanical pressure exerted by a set of respectively
      passive isotropic and self-propelled polar disks onto two different flexible
      unidimensional membranes. In the case of the isotropic disks, the mechanical
      pressure, inferred from the shape of the membrane, is identical for both
      membranes and follows the equilibrium equation of state for hard disks. On the
      contrary, for the self-propelled disks, the mechanical pressure strongly depends
      on the membrane in use and thus is not a state variable. When self-propelled
      disks are present on both sides of the membrane, we observe an instability of the
      membrane akin to the one predicted theoretically for active Brownian particles
      against a soft wall. In that case, the integrated mechanical pressure difference
      across the membrane cannot be computed from the sole knowledge of the packing
      fractions on both sides, further evidence of the absence of an equation of state.

PMID- 28753367
TI  - Exact Nonequilibrium Transport in the Topological Kondo Effect.
AB  - A leading candidate for the experimental confirmation of the nonlocal quantum
      dynamics of Majorana fermions is the topological Kondo effect, predicted for
      mesoscopic superconducting islands connected to metallic leads. We identify an
      anisotropic, Toulouse-like, limit of the topological Kondo problem where the full
      nonequilibrium conductance and shot noise can be calculated exactly. Near the
      Kondo fixed point, we find novel asymptotic features including a universal
      conductance scaling function and fractional charge quantization observable via
      the Fano factor. In the universal regime, our results apply for generic
      anisotropy and even away from the Kondo limit as long as the system supports an
      emergent topological Kondo fixed point. Our approach thus provides key new
      qualitative insights and exact expressions for quantitative comparisons to future
      experimental data.

PMID- 28753368
TI  - Quantum Anomalous Hall State in Ferromagnetic SrRuO_{3} (111) Bilayers.
AB  - SrRuO_{3} heterostructures grown in the (111) direction are a rare example of
      thin film ferromagnets. By means of density functional theory plus dynamical mean
      field theory we show that the half-metallic ferromagnetic state with an ordered
      magnetic moment of 2  MU_{B}/Ru survives the ultimate dimensional confinement
      down to a bilayer, even at elevated temperatures of 500 K. In the minority
      channel, the spin-orbit coupling opens a gap at the linear band crossing
      corresponding to 3/4 filling of the t_{2g} shell. We predict that the emergent
      phase is Haldane's quantum anomalous Hall state with Chern number C=1, without an
      external magnetic field or magnetic impurities.

PMID- 28753369
TI  - Radiative Rotational Lifetimes and State-Resolved Relative Detachment Cross
      Sections from Photodetachment Thermometry of Molecular Anions in a Cryogenic
      Storage Ring.
AB  - Photodetachment thermometry on a beam of OH^{-} in a cryogenic storage ring
      cooled to below 10 K is carried out using two-dimensional frequency- and time
      dependent photodetachment spectroscopy over 20 min of ion storage. In equilibrium
      with the low-level blackbody field, we find an effective radiative temperature
      near 15 K with about 90% of all ions in the rotational ground state. We measure
      the J=1 natural lifetime (about 193 s) and determine the OH^{-} rotational
      transition dipole moment with 1.5% uncertainty. We also measure rotationally
      dependent relative near-threshold photodetachment cross sections for
      photodetachment thermometry.

PMID- 28753370
TI  - Pulsed Entanglement of Two Optomechanical Oscillators and Furry's Hypothesis.
AB  - A strategy for generating entanglement between two separated optomechanical
      oscillators is analyzed, using entangled radiation produced from down-conversion
      and stored in an initiating cavity. We show that the use of pulsed entanglement
      with optimally shaped temporal modes can efficiently transfer quantum
      entanglement into a mechanical mode, then remove it after a fixed waiting time
      for measurement. This protocol could provide new avenues for testing for bounds
      on decoherence in massive systems that are spatially separated, as originally
      suggested by Furry not long after the discussion by Einstein-Podolsky-Rosen and
      Schrodinger of entanglement.

PMID- 28753371
TI  - Erratum: Nonequilibrium Phase Behavior from Minimization of Free Power
      Dissipation [Phys. Rev. Lett. 117, 208003 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.117.208003.

PMID- 28753372
TI  - Towards Holography via Quantum Source-Channel Codes.
AB  - While originally motivated by quantum computation, quantum error correction (QEC)
      is currently providing valuable insights into many-body quantum physics, such as
      topological phases of matter. Furthermore, mounting evidence originating from
      holography research (AdS/CFT) indicates that QEC should also be pertinent for
      conformal field theories. With this motivation in mind, we introduce quantum
      source-channel codes, which combine features of lossy compression and approximate
      quantum error correction, both of which are predicted in holography. Through a
      recent construction for approximate recovery maps, we derive guarantees on its
      erasure decoding performance from calculations of an entropic quantity called
      conditional mutual information. As an example, we consider Gibbs states of the
      transverse field Ising model at criticality and provide evidence that they
      exhibit nontrivial protection from local erasure. This gives rise to the first
      concrete interpretation of a bona fide conformal field theory as a quantum error
      correcting code. We argue that quantum source-channel codes are of independent
      interest beyond holography.

PMID- 28753373
TI  - Compression Freezing Kinetics of Water to Ice VII.
AB  - Time-resolved x-ray diffraction (XRD) of compressed liquid water shows
      transformation to ice VII in 6 nsec, revealing crystallization rather than
      amorphous solidification during compression freezing. Application of classical
      nucleation theory indicates heterogeneous nucleation and one-dimensional (e.g.,
      needlelike) growth. These first XRD data demonstrate rapid growth kinetics of ice
      VII with implications for fundamental physics of diffusion-mediated
      crystallization and thermodynamic modeling of collision or impact events on ice
      rich planetary bodies.

PMID- 28753374
TI  - Continuous Symmetry Breaking in 1D Long-Range Interacting Quantum Systems.
AB  - Continuous symmetry breaking (CSB) in low-dimensional systems, forbidden by the
      Mermin-Wagner theorem for short-range interactions, may take place in the
      presence of slowly decaying long-range interactions. Nevertheless, there is no
      stringent bound on how slowly interactions should decay to give rise to CSB in 1D
      quantum systems at zero temperature. Here, we study a long-range interacting spin
      chain with U(1) symmetry and power-law interactions V(r)~1/r^{alpha}. Using a
      number of analytical and numerical techniques, we find CSB for alpha smaller than
      a critical exponent alpha_{c}(<=3) that depends on the microscopic parameters of
      the model. Furthermore, the transition from the gapless XY phase to the gapless
      CSB phase is mediated by the breaking of conformal and Lorentz symmetries due to
      long-range interactions, and is described by a universality class akin to, but
      distinct from, the Berezinskii-Kosterlitz-Thouless transition. Signatures of the
      CSB phase should be accessible in existing trapped-ion experiments.

PMID- 28753375
TI  - Self-Assembly of Colloidal Molecules due to Self-Generated Flow.
AB  - The emergence of structure through aggregation is a fascinating topic and of both
      fundamental and practical interest. Here we demonstrate that self-generated
      solvent flow can be used to generate long-range attractions on the colloidal
      scale, with subpiconewton forces extending into the millimeter range. We observe
      a rich dynamic behavior with the formation and fusion of small clusters
      resembling molecules. The dynamics of this assembly is governed by an effective
      conservative energy that for large separations r decays as 1/r. Breaking the flow
      symmetry, these clusters can be made active.

PMID- 28753376
TI  - Searching for the QCD Axion with Gravitational Microlensing.
AB  - The phase transition responsible for axion dark matter (DM) production can create
      large amplitude isocurvature perturbations, which collapse into dense objects
      known as axion miniclusters. We use microlensing data from the EROS survey and
      from recent observations with the Subaru Hyper Suprime Cam to place constraints
      on the minicluster scenario. We compute the microlensing event rate for
      miniclusters, treating them as spatially extended objects. Using the published
      bounds on the number of microlensing events, we bound the fraction of DM
      collapsed into miniclusters f_{MC}. For an axion with temperature-dependent mass
      consistent with the QCD axion, we find f_{MC}<0.083(m_{a}/100  MUeV)^{0.12},
      which represents the first observational constraint on the minicluster fraction.
      We forecast that a high-efficiency observation of around ten nights with Subaru
      would be sufficient to constrain f_{MC}?0.004 over the entire QCD axion mass
      range. We make various approximations to derive these constraints, and dedicated
      analyses by the observing teams of EROS and Subaru are necessary to confirm our
      results. If accurate theoretical predictions for f_{MC} can be made in the
      future, then microlensing can be used to exclude or discover the QCD axion.
      Further details of our computations are presented in a companion paper [M.
      Fairbairn, D. J. E. Marsh, J. Quevillon, and S. Rozier (to be published)].

PMID- 28753377
TI  - Expected Number of Fixed Points in Boolean Networks with Arbitrary Topology.
AB  - Boolean network models describe genetic, neural, and social dynamics in complex
      networks, where the dynamics depend generally on network topology. Fixed points
      in a genetic regulatory network are typically considered to correspond to cell
      types in an organism. We prove that the expected number of fixed points in a
      Boolean network, with Boolean functions drawn from probability distributions that
      are not required to be uniform or identical, is one, and is independent of
      network topology if only a feedback arc set satisfies a stochastic neutrality
      condition. We also demonstrate that the expected number is increased by the
      predominance of positive feedback in a cycle.

PMID- 28753378
TI  - 2017 National Standards for Diabetes Self-Management Education and Support.
AB  - Purpose The purpose of this study is to review the literature for Diabetes Self
      Management Education and Support (DSMES) to ensure the National Standards for
      DSMES (Standards) align with current evidence-based practices and utilization
      trends. Methods The 10 Standards were divided among 20 interdisciplinary
      workgroup members. Members searched the current research for diabetes education
      and support, behavioral health, clinical, health care environment, technical,
      reimbursement, and business practice for the strongest evidence that guided the
      Standards revision. Results Diabetes Self-Management Education and Support
      facilitates the knowledge, skills, and ability necessary for diabetes self-care
      as well as activities that assist a person in implementing and sustaining the
      behaviors needed to manage their condition on an ongoing basis. The evidence
      indicates that health care providers and people affected by diabetes are
      embracing technology, and this is having a positive impact of DSMES access,
      utilization, and outcomes. Conclusion Quality DSMES continues to be a critical
      element of care for all people with diabetes. The DSMES services must be
      individualized and guided by the concerns, preferences, and needs of the person
      affected by diabetes. Even with the abundance of evidence supporting the benefits
      of DSMES, it continues to be underutilized, but as with other health care
      services, technology is changing the way DSMES is delivered and utilized with
      positive outcomes.

PMID- 28753379
TI  - Gene Expression Signatures in Tuberculosis Have Greater Overlap with Autoimmune
      Diseases Than with Infectious Diseases.

PMID- 28753380
TI  - CT and MR Imaging of Gynecologic Emergencies.
AB  - Gynecologic emergencies include various diseases that result from adnexal and
      uterine disorders. Adnexal disorders may be classified into the following three
      categories: (a) disorders that cause hemorrhage (hemorrhagic ovarian cysts and
      ectopic pregnancies); (b) disorders related to adnexal tumors (adnexal torsion
      and rupture of ovarian tumors); and (c) disorders related to pelvic inflammatory
      disease, such as tubo-ovarian abscesses. Unusual adnexal torsion, such as massive
      ovarian edema, isolated fallopian tube torsion, and paraovarian cyst torsion, has
      also been described. Uterine disorders in gynecologic emergencies may be
      classified into two categories: (a) acute fibroid complications, including red
      degeneration of a uterine leiomyoma, torsion of subserosal myomas, and torsion of
      the uterus; and (b) causes of acute uterine bleeding, including retained products
      of conception and uterine arteriovenous malformations. Some gynecologic diseases
      are self-limited, while others cause infertility or life-threatening infection or
      bleeding if left untreated. Therefore, prompt and accurate diagnosis is important
      for appropriate life-saving treatment and for the preservation of fertility. The
      imaging findings are important when evaluating acute gynecologic diseases because
      the symptoms and physical examination findings are often nonspecific and limited.
      Ultrasonography is the first-line imaging modality; however, when a definitive
      diagnosis cannot be established, computed tomography (CT) and magnetic resonance
      (MR) imaging may narrow the differential diagnosis. Appropriate management
      requires radiologists to be familiar with the CT and MR imaging features of
      gynecologic emergencies. With respect to rare conditions, radiologists should
      take into account the representative findings presented in this article to
      increase diagnostic accuracy. (c)RSNA, 2017.

PMID- 28753381
TI  - Molecular and Clinical Approach to Intra-abdominal Adverse Effects of Targeted
      Cancer Therapies.
AB  - Targeted cancer therapies encompass an exponentially growing number of agents
      that involve a myriad of molecular pathways. To excel within this rapidly
      changing field of clinical oncology, radiologists must eschew traditional organ
      system-based approaches of cataloging adverse effects in favor of a conceptual
      framework that incorporates molecular mechanisms and associated clinical
      outcomes. Understanding molecular mechanisms that underlie imaging manifestations
      of adverse effects and known associations with treatment response allows
      radiologists to more effectively recognize adverse effects and differentiate them
      from tumor progression. Radiologists can therefore more effectively guide
      oncologists in the management of adverse effects and treatment decisions
      regarding continuation or cessation of drug therapy. Adverse effects from
      targeted cancer therapies can be classified into four categories: (a) category 1,
      on-target adverse effects associated with treatment response; (b) category 2, on
      target adverse effects without associated treatment response; (c) category 3, off
      target adverse effects; and (d) category 4, tumor necrosis-related adverse
      effects. This review focuses on adverse effects primarily within the abdomen and
      pelvis classified according to established or hypothesized molecular mechanisms
      and illustrated with images of classic examples and several potential emerging
      toxic effects. (c)RSNA, 2017.

PMID- 28753382
TI  - Electrical Stimulation of Visual Cortex: Relevance for the Development of Visual
      Cortical Prosthetics.
AB  - Electrical stimulation of the cerebral cortex is a powerful tool for exploring
      cortical function. Stimulation of early visual cortical areas is easily detected
      by subjects and produces simple visual percepts known as phosphenes. A device
      implanted in visual cortex that generates patterns of phosphenes could be used as
      a substitute for natural vision in blind patients. We review the possibilities
      and limitations of such a device, termed a visual cortical prosthetic. Currently,
      we can predict the location and size of phosphenes produced by stimulation of
      single electrodes. A functional prosthetic, however, must produce spatial
      temporal patterns of activity that will result in the perception of complex
      visual objects. Although stimulation of later visual cortical areas alone usually
      does not lead to a visual percept, it can alter visual perception and the
      performance of visual behaviors, and training subjects to use signals injected
      into these areas may be possible.

PMID- 28753383
TI  - Quantifying Heuristic Bias: Anchoring, Availability, and Representativeness.
AB  - : Construct: Authors examined whether a new vignette-based instrument could
      isolate and quantify heuristic bias. BACKGROUND: Heuristics are cognitive
      shortcuts that may introduce bias and contribute to error. There is no
      standardized instrument available to quantify heuristic bias in clinical decision
      making, limiting future study of educational interventions designed to improve
      calibration of medical decisions. This study presents validity data to support a
      vignette-based instrument quantifying bias due to the anchoring, availability,
      and representativeness heuristics. APPROACH: Participants completed
      questionnaires requiring assignment of probabilities to potential outcomes of
      medical and nonmedical scenarios. The instrument randomly presented scenarios in
      one of two versions: Version A, encouraging heuristic bias, and Version B, worded
      neutrally. The primary outcome was the difference in probability judgments for
      Version A versus Version B scenario options. RESULTS: Of 167 participants
      recruited, 139 enrolled. Participants assigned significantly higher mean
      probability values to Version A scenario options (M = 9.56, SD = 3.75) than
      Version B (M = 8.98, SD = 3.76), t(1801) = 3.27, p = .001. This result remained
      significant analyzing medical scenarios alone (Version A, M = 9.41, SD = 3.92;
      Version B, M = 8.86, SD = 4.09), t(1204) = 2.36, p = .02. Analyzing medical
      scenarios by heuristic revealed a significant difference between Version A and B
      for availability (Version A, M = 6.52, SD = 3.32; Version B, M = 5.52, SD =
      3.05), t(404) = 3.04, p = .003, and representativeness (Version A, M = 11.45, SD
      = 3.12; Version B, M = 10.67, SD = 3.71), t(396) = 2.28, p = .02, but not
      anchoring. Stratifying by training level, students maintained a significant
      difference between Version A and B medical scenarios (Version A, M = 9.83, SD =
      3.75; Version B, M = 9.00, SD = 3.98), t(465) = 2.29, p = .02, but not residents
      or attendings. Stratifying by heuristic and training level, availability
      maintained significance for students (Version A, M = 7.28, SD = 3.46; Version B,
      M = 5.82, SD = 3.22), t(153) = 2.67, p = .008, and residents (Version A, M =
      7.19, SD = 3.24; Version B, M = 5.56, SD = 2.72), t(77) = 2.32, p = .02, but not
      attendings. CONCLUSIONS: Authors developed an instrument to isolate and quantify
      bias produced by the availability and representativeness heuristics, and
      illustrated the utility of their instrument by demonstrating decreased heuristic
      bias within medical contexts at higher training levels.

PMID- 28753384
TI  - Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic
      Castration-Resistant Prostate Cancer: A Randomized Phase III Trial-FIRSTANA.
AB  - Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC),
      overall survival (OS) is significantly improved with cabazitaxel versus
      mitoxantrone after prior docetaxel treatment. FIRSTANA ( ClinicalTrials.gov
      identifier: NCT01308567) assessed whether cabazitaxel 20 mg/m2 (C20) or 25 mg/m2
      (C25) is superior to docetaxel 75 mg/m2 (D75) in terms of OS in patients with
      chemotherapy-naive mCRPC. Patients and Methods Patients with mCRPC and Eastern
      Cooperative Oncology Group performance status of 0 to 2 were randomly assigned
      1:1:1 to receive C20, C25, or D75 intravenously every 3 weeks plus daily
      prednisone. The primary end point was OS. Secondary end points included safety;
      progression-free survival (PFS); tumor, prostate-specific antigen, and pain
      response; pharmacokinetics; and health-related quality of life. Results Between
      May 2011 and April 2013, 1,168 patients were randomly assigned. Baseline
      characteristics were similar across cohorts. Median OS was 24.5 months with C20,
      25.2 months with C25, and 24.3 months with D75. Hazard ratio for C20 versus D75
      was 1.01 (95% CI, 0.85 to 1.20; P = .997), and hazard ratio for C25 versus D75
      was 0.97 (95% CI, 0.82 to 1.16; P = .757). Median PFS was 4.4 months with C20,
      5.1 months with C25, and 5.3 months with D75, with no significant differences
      between treatment arms. Radiographic tumor responses were numerically higher for
      C25 (41.6%) versus D75 (30.9%; nominal P = .037, without multiplicity test
      adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%,
      60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia,
      diarrhea, and hematuria were more frequent with C25; peripheral neuropathy,
      peripheral edema, alopecia, and nail disorders were more frequent with D75.
      Conclusion C20 and C25 did not demonstrate superiority for OS versus D75 in
      patients with chemotherapy-naive mCRPC. Tumor response was numerically higher
      with C25 versus D75; pain PFS was numerically improved with D75 versus C25.
      Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall
      less toxicity with C20.

PMID- 28753385
TI  - Is the Relationship Between Pornography Consumption Frequency and Lower Sexual
      Satisfaction Curvilinear? Results From England and Germany.
AB  - Several studies using different methods have found that pornography consumption
      is associated with lower sexual satisfaction. The language used by media-effects
      scholars in discussions of this association implies an expectation that lowered
      satisfaction is primarily due to frequent-but not infrequent-consumption. Actual
      analyses, however, have assumed linearity. Linear analyses presuppose that for
      each increase in the frequency of pornography consumption there is a
      correspondingly equivalent decrease in sexual satisfaction. The present brief
      report explored the possibility that the association is curvilinear. Survey data
      from two studies of heterosexual adults, one conducted in England and the other
      in Germany, were employed. Results were parallel in each country and were not
      moderated by gender. Quadratic analysis indicated a curvilinear relationship, in
      the form of a predominantly negative, concave downward curve. Simple slope
      analyses suggested that when the frequency of consumption reaches once a month,
      sexual satisfaction begins to decrease, and that the magnitude of the decrease
      becomes larger with each increase in the frequency of consumption. The
      observational nature of the data employed precludes any causal inferences.
      However, if an effects perspective was adopted, these results would suggest that
      low rates of pornography consumption have no impact on sexual satisfaction and
      that adverse effects initiate only after consumption reaches a certain frequency.

PMID- 28753386
TI  - Where Do Inhaled Fossil Fuel-derived Particles Go?

PMID- 28753387
TI  - Assessing Prejudice Toward Two-Father Parenting and Two-Mother Parenting: The
      Beliefs on Same-Sex Parenting Scale.
AB  - This article describes two interrelated studies that investigated beliefs and
      stereotypes on two-father parenting and two-mother parenting through the
      development and validation of the Beliefs on Same-Sex Parenting (BOSSP) scale.
      The BOSSP captures two beliefs: (1) prejudices toward same-sex couples' inherent
      inability to parent and (2) concerns about same-sex parenting that are not
      necessarily related to homonegativity. In Study 1 (301 heterosexual
      participants), exploratory factor analysis (EFA) suggested an 11-item scale for
      attitudes toward both two-father families and two-mother families, with two
      factors: parenting skills, which evaluates beliefs on same-sex couples' ability
      to take care of their children; and parental adjustment, which assesses beliefs
      on the impact of challenges related to same-sex parenting on children's well
      being. Support for convergent validity between BOSSP factor scores and those of
      theoretically related measures were provided. In Study 2 (346 heterosexual
      participants surveyed in two time points), CFA indicated that the two-factor
      model provided the best fit. Test-retest reliability and longitudinal invariance
      were documented. Finally, results revealed that more negative attitudes toward
      same-sex parenting were held by men than by women and were associated with
      negative opinions on reproductive techniques. The innovative characteristics of
      the BOSSP and implications for future practice are discussed.

PMID- 28753388
TI  - Downregulation of MicroRNA-126 Augments DNA Damage Response in Cigarette Smokers
      and Patients with Chronic Obstructive Pulmonary Disease.

PMID- 28753389
TI  - Feasibility of Dose-reduced Chest CT with Photon-counting Detectors: Initial
      Results in Humans.
AB  - Purpose To investigate whether photon-counting detector (PCD) technology can
      improve dose-reduced chest computed tomography (CT) image quality compared with
      that attained with conventional energy-integrating detector (EID) technology in
      vivo. Materials and Methods This was a HIPAA-compliant institutional review board
      approved study, with informed consent from patients. Dose-reduced spiral
      unenhanced lung EID and PCD CT examinations were performed in 30 asymptomatic
      volunteers in accordance with manufacturer-recommended guidelines for CT lung
      cancer screening (120-kVp tube voltage, 20-mAs reference tube current-time
      product for both detectors). Quantitative analysis of images included measurement
      of mean attenuation, noise power spectrum (NPS), and lung nodule contrast-to
      noise ratio (CNR). Images were qualitatively analyzed by three radiologists
      blinded to detector type. Reproducibility was assessed with the intraclass
      correlation coefficient (ICC). McNemar, paired t, and Wilcoxon signed-rank tests
      were used to compare image quality. Results Thirty study subjects were evaluated
      (mean age, 55.0 years +/- 8.7 [standard deviation]; 14 men). Of these patients,
      10 had a normal body mass index (BMI) (BMI range, 18.5-24.9 kg/m2; group 1), 10
      were overweight (BMI range, 25.0-29.9 kg/m2; group 2), and 10 were obese (BMI
      >=30.0 kg/m2, group 3). PCD diagnostic quality was higher than EID diagnostic
      quality (P = .016, P = .016, and P = .013 for readers 1, 2, and 3, respectively),
      with significantly better NPS and image quality scores for lung, soft tissue, and
      bone and with fewer beam-hardening artifacts (all P < .001). Image noise was
      significantly lower for PCD images in all BMI groups (P < .001 for groups 1 and
      3, P < .01 for group 2), with higher CNR for lung nodule detection (12.1 +/- 1.7
      vs 10.0 +/- 1.8, P < .001). Inter- and intrareader reproducibility were good (all
      ICC > 0.800). Conclusion Initial human experience with dose-reduced PCD chest CT
      demonstrated lower image noise compared with conventional EID CT, with better
      diagnostic quality and lung nodule CNR. (c) RSNA, 2017 Online supplemental
      material is available for this article.

PMID- 28753391
TI  - Differences in forearm strength, endurance, and hemodynamic kinetics between male
      boulderers and lead rock climbers.
AB  - This study examined differences in the oxygenation kinetics and strength and
      endurance characteristics of boulderers and lead sport climbers. Using near
      infrared spectroscopy, 13-boulderers, 10-lead climbers, and 10-controls completed
      assessments of oxidative capacity index and muscle oxygen consumption (m?O2) in
      the flexor digitorum profundus (FDP), and extensor digitorum communis (EDC).
      Additionally, forearm strength (maximal volitional contraction MVC), endurance
      (force-time integral FTI at 40% MVC), and forearm volume (FAV and DeltaFAV) was
      assessed. MVC was significantly greater in boulderers compared to lead climbers
      (mean difference = 9.6, 95% CI 5.2-14 kg). FDP and EDC oxidative capacity indexes
      were significantly greater (p = .041 and .013, respectively) in lead climbers and
      boulderers compared to controls (mean difference = -1.166, 95% CI (-3.264 to
      0.931 s) and mean difference = -1.120, 95% CI (-3.316 to 1.075 s), respectively)
      with no differences between climbing disciplines. Climbers had a significantly
      greater FTI compared to controls (mean difference = 2205, 95% CI= 1114-3296 and
      mean difference = 1716, 95% CI = 553-2880, respectively) but not between
      disciplines. There were no significant group differences in DeltaFAV or m?O2. The
      greater MVC in boulderers may be due to neural adaptation and not hypertrophy. A
      greater oxidative capacity index in both climbing groups suggests that
      irrespective of climbing discipline, trainers, coaches, and practitioners should
      consider forearm specific aerobic training to aid performance.

PMID- 28753392
TI  - Cortical Button Versus Cross-pin Femoral Fixation for Hamstring Anterior Cruciate
      Ligament Reconstruction: A Meta-analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Incidences of graft rupture are associated with postoperative knee
      laxity after anterior cruciate ligament (ACL) reconstruction. Reports of
      postoperative knee laxity after ACL reconstruction using different femoral
      fixation techniques in several studies are controversial. PURPOSE: To compare,
      via meta-analysis of randomized controlled trials (RCTs), the clinical outcomes
      and postoperative knee laxity of autogenous hamstring ACL reconstruction using
      cortical button versus cross-pin femoral fixation. STUDY DESIGN: Meta-analysis.
      METHODS: This study followed the PRISMA (Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses) guidelines. The online PubMed, EMBASE, and Cochrane
      Central Register of Controlled Trials databases were searched from inception to
      April 1, 2017. The study included only level 1 or 2 RCTs that compared cortical
      button and cross-pin femoral fixation for ACL reconstruction with hamstring
      autografts and that reported clinical outcomes or postoperative knee laxity. The
      Cochrane Collaboration's risk of bias tool was used to assess the risk of bias
      for all included studies. For the meta-analysis, the investigators extracted data
      on clinical outcomes measured by postoperative International Knee Documentation
      Committee (IKDC) score or Lysholm score and postoperative knee laxity defined as
      >5 mm side-to-side difference by the arthrometric measurement, Lachman test >=2+,
      and pivot-shift test >=2+. The risk ratio (RR) and its corresponding 95%
      confidence interval (CI) were computed for dichotomous data. Heterogeneity was
      assessed by I2 tests. RESULTS: A total of 6 RCTs with 445 patients were included.
      Statistical analysis of pooled data showed no significant difference between the
      cortical button and cross-pin groups on postoperative IKDC score (RR, 0.94; 95%
      CI, 0.88-1.02; P = .13; I2 = 4%) and Lysholm score (RR, 0.97; 95% CI, 0.91-1.04;
      P = .45; I2 = 0%). Postoperative knee laxity was reported in 5 studies, and no
      significant difference was found between the 2 groups (RR, 1.49; 95% CI, 0.83
      2.68; P = .18; I2 = 37%). CONCLUSION: Cortical button femoral fixation for
      autogenous hamstring ACL reconstruction had no significant difference in terms of
      clinical outcomes and postoperative knee laxity compared with cross-pin femoral
      fixation.

PMID- 28753393
TI  - "I Swear I Will Never Betray You": Factors Reported by Spouses as Helping Them
      Resist Extramarital Sex in Relation to Gender, Marriage Length, and Religiosity.
AB  - Studies suggest that married people frequently engage in intimate relationships
      with people other than their spouses, and the literature has extensively examined
      motives for doing so. However, less is known about what factors prevent spouses
      from engaging in extramarital sex. While investment theory, interdependence
      theory, and moral theories offer insights into this question, they have not been
      subject to much empirical research. We examine these theories in relation to
      several characteristics of individuals and couples: gender, length of the
      marriage, and religiosity. In two studies, 423 participants completed a
      questionnaire on the perceived importance of 29 reasons to resist the temptation
      for extramarital sex. Participants also reported the likelihood that they would
      engage in extramarital sex if the opportunity presented itself. Results show that
      being female, more religious, and married for less time were associated with
      greater expectations of refraining from extramarital sex when presented with a
      hypothetical scenario. Multiple hierarchical regression showed that among factors
      relevant to conscious decision making, moral standards and fundamental anxieties
      (fear of remaining alone) predict expectations of refraining from extramarital
      sex better than concerns about effects on the children or the other participant.

PMID- 28753394
TI  - Ladies First? Not So Fast: Linguistic Sexism in Peer-Reviewed Research.
AB  - The words we use reflect and influence our interpretation of the world. The role
      of gender within a language varies; biases based on social gender are referred to
      as linguistic sexism. Male firstness is the practice of persistently ordering
      masculine terms before feminine terms. Because academic writing is mandated to be
      free of bias, peer-reviewed research should not contain any form of linguistic
      sexism. To assess the presence of male firstness in academic writing, we examined
      862 contemporary articles from 10 social science journals across three
      disciplines: sexuality, health, and psychology. To assess male firstness, we
      tallied common gendered pairs (e.g., "women and men"; "male and female") and
      calculated percentages indicating how often men were presented before women. We
      found that male firstness bias was present in each of the 10 journals. For
      individual journals, the percentage of gendered phrases that presented masculine
      terms first ranged from 57.7% to 88.8%. Sexuality and health journals
      demonstrated less linguistic sexism than psychology; however, there were no
      consistent trends between journals within each discipline. We discuss the current
      presence of male firstness in academic journals and the issues this bias
      triggers. Recommendations for reducing linguistic sexism in peer-reviewed
      research are also discussed.

PMID- 28753395
TI  - Neurocognitive Impairment in a Chronically Well-Suppressed HIV-Infected
      Population: The Dutch TREVI Cohort Study.
AB  - We assessed the value of screening for cognitive abnormalities in a chronically
      infected HIV population (N = 388) and investigated the association with clinical
      correlates. The mean age was 48 years (+/-11), the majority of the patients were
      male (89%), the median duration of infection was 6 years [interquartile range
      (IQR) = 2-12], the median CD count was 600 (IQR = 450-780), and 326 (84%) had a
      viral load below 200 copies/mL. Screening for cognitive complaints was applied
      using the three Simioni questions and the international HIV dementia scale
      (iHDS). Neuropsychological assessment (NPA) included 13 well-validated tests
      assessing motor speed, concentration, and memory. A total of 69 patients
      completed the NPA. CD4 (nadir), viral load, combination antiretroviral therapy
      (cART) duration, and the presence of comorbidities were evaluated for
      associations with NPA result. A total of 127 (33%) reported cognitive complaints
      during screening. The sensitivity and specificity of the Simioni questions were
      82% and 24%, respectively. Adding the iHDS resulted in a sensitivity of 50% and a
      specificity of 73%. A CD4 nadir count <50 cells/m3 was associated with an
      abnormal NPA (p = 0.01). Comorbidities were more prevalent in patients with an
      abnormal NPA, although not statistically significant (p = 0.276). Age, current
      CD4, viral load, and cART duration were not associated with abnormal NPA. The
      authors conclude that current screening strategies are insufficient in detecting
      HIV-associated neurocognitive disorder. A low CD4 nadir is associated with poor
      neurocognitive outcome in HIV.

PMID- 28753396
TI  - Young Men's Disclosure of Same Sex Behaviors to Healthcare Providers and the
      Impact on Health: Results from a US National Sample of Young Men Who Have Sex
      with Men.
AB  - Many men who have sex with men (MSM) do not disclose their same sex behaviors to
      healthcare providers (HCPs). We used a series of logistic regression models to
      explore a conceptual framework that first identified predictors of disclosure to
      HCPs among young MSM (YMSM), and subsequently examined young men's disclosure of
      male-male sexual behaviors to HCPs as a mediator between sociodemographic and
      behavioral factors and three distinct health outcomes [HIV testing, sexually
      transmitted infection (STI) testing, and human papillomavirus (HPV) vaccination].
      We determined the predictors of disclosure to HCPs among YMSM and examined the
      relationship between disclosure and the receipt of appropriate healthcare
      services. Data were collected online through a US national sample of 1750 YMSM
      (ages 18-29 years) using a social and sexual networking website for MSM. Sexual
      history, STI/HIV screening history, sexual health, and patient-provider
      communication were analyzed in the logistic regression models. Participants were
      predominantly white (75.2%) and gay/homosexual (76.7%) with at least some college
      education (82.7%). Young men's disclosure of male-male sexual behaviors to HCPs
      was associated with the receipt of all healthcare outcomes in our model.
      Disclosure was a stronger mediator in HPV vaccination than in HIV and STI
      testing. Disclosure to non-HCP friends and family, HCP visit in the past year,
      and previous STI diagnosis were the strongest predictors of disclosure. Young
      men's disclosure of male-male sexual behaviors to HCPs is integral to the receipt
      of appropriate healthcare services among YMSM. HPV vaccination is more dependent
      on provider-level interaction with patients than HIV/STI testing.

PMID- 28753397
TI  - Lateral Meniscal Allograft Transplant via a Medial Approach Leads to Less
      Extrusion.
AB  - BACKGROUND: Accurate positioning of the bony bridge is crucial to prevent
      extrusion of meniscal allografts after transplant. However, oblique or
      lateralized placement of the bony bridge of the lateral meniscal allograft may
      occur due to technical error or a limited visual field. The patellar tendon may
      be an obstacle to approaching the anterior horn of the lateral meniscus,
      resulting in a laterally placed allograft. Therefore, lateral meniscal transplant
      through a medial arthrotomy would be an alternative approach. However, no report
      exists regarding allograft extrusion when comparing medial and lateral arthrotomy
      techniques in lateral meniscal transplants. HYPOTHESIS: Extrusion of the midbody
      of the allograft is less severe and the rotation of the bony bridge is less
      oblique in lateral meniscal allograft transplants through the medial parapatellar
      approach than those through the lateral approach. STUDY DESIGN: Cohort study;
      Level of evidence, 3. METHODS: A bony bridge was used to perform 55 lateral
      meniscal transplants through either a medial or a lateral arthrotomy. Thirty-two
      allografts were transplanted through a medial arthrotomy and 23 were transplanted
      through a lateral arthrotomy, not randomly. Because correct positioning of the
      bony trough through the medial arthrotomy was easier than that through the
      lateral arthrotomy, the method of the arthrotomy was changed for the latter. The
      procedure for both groups was identical except for the arthrotomy technique, and
      rehabilitation was identical for both groups. Follow-up magnetic resonance
      imaging was conducted for all patients to measure the postoperative extrusion and
      obliquity of the bony bridge of the allograft. On the coronal view, extrusion was
      measured as the distance between the outer edge of the articular cartilage of the
      lateral tibial plateau and the outer edge of the meniscal allograft. On the axial
      view, a line (line B) was drawn along the longitudinal axis of the bony bridge.
      The posterior tibial condylar tangential line was drawn between the medial and
      lateral posterior tibial condylar cortices. A line (line T) was drawn
      perpendicular to the posterior tibial condylar tangential line. The angle (trough
      angle) between lines B and T was measured. Postoperative extrusion and the trough
      angle were compared between the medial and lateral arthrotomy groups. RESULTS:
      The median extrusion of the midbody of the allograft was 2.2 mm (interquartile
      range [IQR], 2.4 mm; range, 0-4.6 mm) in the medial arthrotomy group and 3.1 mm
      (IQR, 1.5 mm; range, 0-5.3 mm) in the lateral arthrotomy group ( P = .001). Seven
      (21.9%) patients demonstrated extrusion in the medial arthrotomy group, and 15
      (65.2%) patients had extrusion in the lateral group ( P = .002). The median
      trough angle was 0.9 degrees  (IQR, 9.3 degrees ; range, -8.8-15.8 degrees ) in
      the medial arthrotomy group and 11.6 degrees  (IQR, 2.8 degrees ; range, 3-19.8
      degrees ) in the lateral arthrotomy group ( P < .001). CONCLUSION: Based on this
      experience, lateral meniscal allograft transplant through a medial arthrotomy is
      preferred to decrease postoperative extrusion of the allograft.

PMID- 28753398
TI  - Resumenes al Espanol.

PMID- 28753399
TI  - Disability Policy Implementation From a Cross-Cultural Perspective.
AB  - Implementation of disability policy is influenced by social, political, and
      cultural factors. Based on published work, this article discusses four guidelines
      considered critical for successful policy implementation from a cross-cultural
      perspective. These guidelines are to: (a) base policy implementation on a
      contextual analysis, (b) employ a value-based approach, (c) align the service
      delivery system both vertically and horizontally, and (d) engage in a partnership
      in policy implementation. Public policy should be understood from a systems
      perspective that includes cross-cultural issues, such as how different
      stakeholders are acting and the way they plan and implement policy.

PMID- 28753400
TI  - A Model for Analyzing Disability Policy.
AB  - This article describes a 12-step model that can be used for policy analysis. The
      model encompasses policy development, implementation, and evaluation; takes into
      account structural foundations of policy; addresses both legal formalism and
      legal realism; demonstrates contextual sensitivity; and addresses application
      issues and different conceptualizations of IDD.

PMID- 28753401
TI  - An Integrated Approach to Disability Policy Development, Implementation, and
      Evaluation.
AB  - This article provides a framework for an integrated approach to disability policy
      development, implementation, and evaluation. The article discusses how a
      framework that combines systems thinking and valued outcomes can be used by
      coalition partners across ecological systems to implement disability policy,
      promote the effective use of resources, incorporate specific support strategies
      that advance identified disability policy goals and lead to systemic changes and
      enhanced personal outcomes, and focus on activities that advance a unified vision
      for disability policy and the attainment of personal outcomes. The article
      concludes with a discussion of the significant challenges and opportunities
      regarding an integrated approach to disability policy in a time of change.

PMID- 28753402
TI  - Intellectual Disability Policy as Developed, Expressed, and Evaluated in
      AAIDD/The Arc Joint Statements: The Role of Organization Position Statements.
AB  - The American Association on Intellectual and Developmental Disabilities (AAIDD)
      and The Arc of the United States (The Arc) have a long history of joined efforts
      to develop, express, and evaluate disability policies. These efforts have
      resulted in a series of formal statements on critical issues such as education,
      healthcare, human rights, and criminal justice. Their joint efforts further
      important policy goals including providing clear strong communication about
      important policy values and directions, promulgating key principles of high
      quality supports and services, affirming best professional practices, and
      emphasizing personal outcomes. In addition, the joint efforts (a) affirm
      important aspects of organization identity; (b) enhance the organizations'
      abilities to assure the input of a wide variety of perspectives; (c) engage
      members' expanded ranges of experiences and talents; (d) multiply staff and
      leadership resources; (e) increase communication strength and avenues; and (f)
      establish processes for timely review and revision of policies as critical
      disability issues arise or change, and new opportunities for policy integration
      and advancement occur. This article describes the processes used to develop,
      express, and evaluate the position statements; summarizes the policy content of
      several joint statements; and discusses the role of these organization position
      statements.

PMID- 28753403
TI  - Disability Policy Evaluation: Combining Logic Models and Systems Thinking.
AB  - Policy evaluation focuses on the assessment of policy-related personal, family,
      and societal changes or benefits that follow as a result of the interventions,
      services, and supports provided to those persons to whom the policy is directed.
      This article describes a systematic approach to policy evaluation based on an
      evaluation framework and an evaluation process that combine the use of logic
      models and systems thinking. The article also includes an example of how the
      framework and process have recently been used in policy development and
      evaluation in Flanders (Belgium), as well as four policy evaluation guidelines
      based on relevant published literature.

PMID- 28753404
TI  - Introduction to the Special Issue on Disability Policy in a Time of Change.
AB  - The enormous effects of public policy-both for good and for ill-in the lives of
      people with intellectual disability and related developmental disabilities demand
      the development of stronger tools for policy analysis, and more effective
      strategies for policy implementation and evaluation. The purpose of this special
      issue is to help readers understand the complexities of disability policy and the
      factors that influence its successful development, implementation, and
      evaluation; and to encourage readers to expand their thinking and actions
      regarding the role they play in disability policy in a time of change.

PMID- 28753405
TI  - Resumes en Francais.

PMID- 28753406
TI  - Association of Established Thyroid-stimulating Hormone and Free Thyroxine Genetic
      Variants with Hashimoto's Thyroiditis.
AB  - Hashimoto's thyroiditis (HT), the most frequent autoimmune thyroid disease
      (AITD), is characterized by chronic inflammation of the thyroid gland that
      usually results in hypothyroidism. Thyroid-stimulating hormone (TSH) and free
      thyroxine (FT4) levels are used as clinical determinants of thyroid function. The
      main aim of this study was to explore the association of established TSH and FT4
      genetic variants with HT. We performed a case-control analysis using 23 genetic
      markers in 200 HT patients and 304 controls. Additionally, we tested the
      association of selected variants with several thyroid-related quantitative traits
      in HT cases only. Two genetic variants showed nominal association with HT:
      rs11935941 near NR3C2 gene (p = 0.0034, OR = 0.57, 95% CI = 0.39-0.83) and
      rs1537424 near MBIP gene (p = 0.0169, OR = 0.72, 95% CI = 0.55-0.94).
      Additionally, three SNPs showed nominal association with thyroglobulin antibody
      (TgAb) levels: rs4804416 in INSR gene (p = 0.0073, beta = -0.51), rs6435953 near
      IGFBP5 gene (p = 0.0081, beta = 0.75), and rs1537424 near MBIP gene (p = 0.0117,
      beta = 0.49). GLIS3 genetic variant rs10974423 showed nominal association with
      thyroid peroxidase antibody (TPOAb) levels (p = 0.0465, beta = -0.56) and NRG1
      genetic variant rs7825175 was nominally associated with thyroid gland volume (p =
      0.0272, beta = -0.18). All detected loci were previously related to thyroid
      function or pathology. Findings from our study suggest biological relevance of
      NR3C2 and MBIP with HT, although these loci require additional confirmation in a
      larger replication study.

PMID- 28753407
TI  - IL-29 Enhances CXCL10 Production in TNF-alpha-stimulated Human Oral Epithelial
      Cells.
AB  - Interleukin-29 (IL-29) is a cytokine belonging to the Type III interferon family.
      It was recently detected in the gingival crevicular fluid of periodontitis
      patients. However, the role of IL-29 in the pathogenesis of periodontal disease
      remains unknown. The aim of this study was to examine the effects of IL-29 on C-X
      C motif chemokine ligand 10 (CXCL10) production in human oral epithelial cells.
      We measured CXCL10 production in TR146 cells, which is a human oral epithelial
      cell line, using an enzyme-linked immunosorbent assay. We used a Western blot
      analysis to detect IL-29 receptor expression and the phosphorylation levels of
      signal transduction molecules, including p38 mitogen-activated protein kinases
      (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear
      factor (NF)- kappaB p65, in the TR146 cells. The TR146 cells expressed the IL-29
      receptor. IL-29 induced CXCL10 production in the TR146 cells. IL-29 significantly
      enhanced CXCL10 production in tumor necrosis factor (TNF)-alpha-stimulated TR146
      cells. The p38 MAPK, STAT3, and NF-kappaB pathways were found to be related to
      the IL-29-induced enhancement of CXCL10 production in TNF-alpha-stimulated TR146
      cells. IL-29 promotes T helper 1-cell accumulation in periodontal lesions by
      inducing CXCL10 production in oral epithelial cells.

PMID- 28753408
TI  - Contribution of monoamine oxidases to vascular oxidative stress in patients with
      end-stage renal disease requiring hemodialysis.
AB  - Arteriovenous fistula (AVF) is the "lifeline" for patients with end-stage renal
      disease (ESRD) undergoing hemodialysis. AVF maturation failure is a poorly
      understood process, one of the contributors being endothelial dysfunction due to
      oxidative stress. Monoamine oxidases (MAOs) A and B were recently identified as
      novel sources of vascular oxidative stress. The aim of the present study was to
      assess the contribution of MAOs to the endothelial dysfunction in patients with
      ESDR with indication of hemodialysis. Fragments of brachial artery collaterals
      were harvested from ESRD patients during the surgical procedure aimed at creating
      the vascular access in the cubital fossa. The effect of increasing concentrations
      (10, 30, 100 MUmol/L) of the irreversible MAO-A inhibitor, clorgyline, and MAO-B
      inhibitor, selegiline, on endothelial-dependent relaxation (EDR) in response to
      cumulative doses of acetylcholine was studied in isolated phenylephrine
      preconstricted vascular rings. Hydrogen peroxide (H2O2) production was assessed
      using ferrous oxidation xylenol orange assay. We showed that incubation of
      brachial rings with MAO inhibitors significantly improved EDR and attenuated H2O2
      generation in patients with ESRD. MAO-related oxidative stress might contribute
      to the primary dysfunction/non-maturation of the AVF and MAO inhibitors could
      improve maturation and long-term patency of the vascular access in dialysis
      patients.

PMID- 28753409
TI  - PCR cycles above routine numbers do not compromise high-throughput DNA barcoding
      results.
AB  - High-throughput DNA barcoding has become essential in ecology and evolution, but
      some technical questions still remain. Increasing the number of PCR cycles above
      the routine 20-30 cycles is a common practice when working with old-type
      specimens, which provide little amounts of DNA, or when facing annealing issues
      with the primers. However, increasing the number of cycles can raise the number
      of artificial mutations due to polymerase errors. In this work, we sequenced 20
      COI libraries in the Illumina MiSeq platform. Libraries were prepared with 40,
      45, 50, 55, and 60 PCR cycles from four individuals belonging to four species of
      four genera of cephalopods. We found no relationship between the number of PCR
      cycles and the number of mutations despite using a nonproofreading polymerase.
      Moreover, even when using a high number of PCR cycles, the resulting number of
      mutations was low enough not to be an issue in the context of high-throughput DNA
      barcoding (but may still remain an issue in DNA metabarcoding due to chimera
      formation). We conclude that the common practice of increasing the number of PCR
      cycles should not negatively impact the outcome of a high-throughput DNA
      barcoding study in terms of the occurrence of point mutations.

PMID- 28753410
TI  - Pyrimido[4,5-b]indole derivatives and use thereof in the expansion of
      hematopoietic stem cells US2015011543 (a1): a patent evaluation.
AB  - INTRODUCTION: There is an unmet need of strategies for ex-vivo expansion of
      hematopoetic stem cells (HSCs) without loss of their primitive nature or
      stemness. We evaluate here a patent that attempts to address this need via key
      small molecules 1 and 40 that possess a pyrimido[4,5-b]indole core. Areas
      covered: (i) Discussion on literature reports of diverse strategies for ex-vivo
      expansion of stem cells. (ii) Synthetic scheme to 1, and general synthetic
      schemes for compounds 1-55 reported in the patent application. (iii) Analysis of
      the in vitro biological data for 1 and 40. Highlight here is: 1 and 40 when used
      in combination with StemReginin1 (SR1), an established aryl hydrocarbon receptor
      antagonist known for ex-vivo HSC expansion, demonstrate better HSC expansion
      relative to SR1 alone. (iv) Analysis of the in vivo biological data for 1 and 40.
      Expert opinion: Compelling evidence on the molecular mechanism of action of 1 and
      40 is not provided making it difficult to optimize this series. It is suggested
      here that combining these molecules with homing molecules will possibly improve
      overall engraftment time and hematopoietic recovery. The numerous literature
      reports and biological data indicates that these pyrimido[4,5-b]indole
      derivatives are promising candidates for the development of potential therapies
      for hematopoietic ailments.

PMID- 28753411
TI  - Mass Mortality Attributed to Acanthocephaliasis at a Gull-billed Tern
      (Gelochelidon nilotica) Colony in Coastal California, USA.
AB  - From 12 May 2013 to 29 May 2013, the Gull-billed Tern (Gelochelidon nilotica)
      colony at the San Diego Bay National Wildlife Refuge, California, US, experienced
      a mass die-off of at least 92 adults, representing 71-92% of the breeding
      population on the US west coast. Cause of death was determined to be peritonitis
      due to perforations of the intestine by a large quantity of acanthocephala
      (Profilicollis [=Polymorphus] altmani). This is a unique report of P. altmani
      infecting G. nilotica, and a report of a great impact to a tern population in
      southern California. Mole crabs (Emerita analoga), the intermediate host for P.
      altmani and a major component of the Gull-billed Tern diet in San Diego, were
      found in the stomachs of necropsied terns along with cystacanths, and are the
      presumed source of the parasite infection. The tern's dietary reliance upon mole
      crabs likely amplified parasite transmission and infection. We suggest additional
      research to determine factors that influence parasite infection of intermediate
      and definitive hosts, particularly mole crabs, given that they are a vital
      resource for migrating birds within the coastal zone.

PMID- 28753412
TI  - INFLUENCE OF SNOWFALL ON BLOOD LEAD LEVELS OF FREE-FLYING BALD EAGLES (HALIAEETUS
      LEUCOCEPHALUS) IN THE UPPER MISSISSIPPI RIVER VALLEY.
AB  - Lead poisoning of scavenging raptors occurs primarily via consumption of game
      animal carcasses containing lead, which peaks during fall firearm hunting
      seasons. We hypothesized that snowfall would mitigate exposure by concealing
      carcasses. We categorized blood lead level (BLL) for a subsample of Bald Eagles
      (Haliaeetus leucocephalus) from the Upper Mississippi River Valley and described
      BLL with respect to age, sex, and snowfall. We captured Bald Eagles overwintering
      in the Upper Mississippi River Valley (n=55) between December 1999 and January
      2002. Individual BLL ranged from nondetectable to 335 MUg/dL, with 73% of the
      samples testing positive for acute exposure to lead. Eagle BLL did not
      significantly differ between age or sex, but levels were higher immediately
      following the hunting season, and they were lower when the previous month's
      snowfall was greater than 11 cm. This study suggests a window of time between the
      white-tailed deer (Odocoileus virginianus) hunting season and the onset of snow
      when the population experienced peak exposure to lead. Combining these findings
      with existing research, we offer a narrative of the annual lead exposure cycle of
      Upper Mississippi River Valley Bald Eagles. These temporal associations are
      necessary considerations for accurate collection and interpretation of BLL.

PMID- 28753413
TI  - Anophthalmia in a Wild Eastern Gray Squirrel (Sciurus carolinensis).
AB  - We describe bilateral true anophthalmia in a juvenile female eastern gray
      squirrel (Sciurus carolinensis) with histologic confirmation that orbital
      contents lacked ocular tissues. Additionally, the optic chiasm of the brain was
      absent and axon density in the optic tract adjacent to the lateral geniculate
      nucleus was reduced.

PMID- 28753414
TI  - A synthesis of studies of access point density as a risk factor for road
      accidents.
AB  - Studies of the relationship between access point density (number of access
      points, or driveways, per kilometre of road) and accident frequency or rate
      (number of accidents per unit of exposure) have consistently found that accident
      rate increases when access point density increases. This paper presents a formal
      synthesis of the findings of these studies. It was found that the addition of one
      access point per kilometre of road is associated with an increase of 4% in the
      expected number of accidents, controlling for traffic volume. Although studies
      consistently indicate an increase in accident rate as access point density
      increases, the size of the increase varies substantially between studies. In
      addition to reviewing studies of access point density as a risk factor, the paper
      discusses some issues related to formally synthesising regression coefficients by
      applying the inverse-variance method of meta-analysis.

PMID- 28753415
TI  - Macro-level vulnerable road users crash analysis: A Bayesian joint modeling
      approach of frequency and proportion.
AB  - This study aims at contributing to the literature on pedestrian and bicyclist
      safety by building on the conventional count regression models to explore
      exogenous factors affecting pedestrian and bicyclist crashes at the macroscopic
      level. In the traditional count models, effects of exogenous factors on non
      motorist crashes were investigated directly. However, the vulnerable road users'
      crashes are collisions between vehicles and non-motorists. Thus, the exogenous
      factors can affect the non-motorist crashes through the non-motorists and vehicle
      drivers. To accommodate for the potentially different impact of exogenous factors
      we convert the non-motorist crash counts as the product of total crash counts and
      proportion of non-motorist crashes and formulate a joint model of the negative
      binomial (NB) model and the logit model to deal with the two parts, respectively.
      The formulated joint model is estimated using non-motorist crash data based on
      the Traffic Analysis Districts (TADs) in Florida. Meanwhile, the traditional NB
      model is also estimated and compared with the joint model. The result indicates
      that the joint model provides better data fit and can identify more significant
      variables. Subsequently, a novel joint screening method is suggested based on the
      proposed model to identify hot zones for non-motorist crashes. The hot zones of
      non-motorist crashes are identified and divided into three types: hot zones with
      more dangerous driving environment only, hot zones with more hazardous walking
      and cycling conditions only, and hot zones with both. It is expected that the
      joint model and screening method can help decision makers, transportation
      officials, and community planners to make more efficient treatments to
      proactively improve pedestrian and bicyclist safety.

PMID- 28753416
TI  - Second harmonic reflection and transmission from primary S0 mode Lamb wave
      interacting with a localized microscale damage in a plate: A numerical
      perspective.
AB  - Second harmonic generation has been widely used in characterizing microstructural
      changes which are evenly distributed in a whole structure. However, few attention
      has been paid to evaluating localized micro-scale damages. In this paper, second
      harmonic reflection and transmission from the primary S0 mode Lamb wave
      interacting with a localized microstructural damage is numerically discussed.
      Schematic diagram for deriving fundamental temporal waveform and reconstructing
      the second harmonic temporal waveform based on Morlet wavelet transform is
      presented. Second harmonic reflection and transmission from an interface between
      the zones of linear elastic and nonlinear materials is firstly studied to verify
      the existence of interfacial nonlinearity. Compositions contributing to second
      harmonic components in the reflected and transmitted waves are analyzed.
      Amplitudes of the reflected and transmitted second harmonic components generated
      at an interface due to the interfacial nonlinearity are quantitatively evaluated.
      Then, second harmonic reflection and transmission from a localized microscale
      damage is investigated. The effects of the length and width of a microscale
      damage on WCPA (wavelet coefficient profile area) of the reflected and
      transmitted second harmonic components are studied respectively. It is found that
      the second harmonic component in the reflected waves mainly reflects the
      interfacial nonlinearity while second harmonic in the transmitted waves reflects
      the material nonlinearity. These findings provide some basis on using second
      harmonic generation for characterization and detection of localized
      microstructural changes.

PMID- 28753417
TI  - Ex vivo determined experimental correction factor for the ultrasonic source term
      in the bioheat equation.
AB  - The objective of this work is to propose an effective absorption coefficient
      (alphaeffec) as an empirical correction factor in the source term of the bioheat
      equation. The temperature rise in biological tissue due to ultrasound
      insonification is produced by energy absorption. Usually, the ultrasonic
      absorption coefficient (alphaA) is used as a source term in the bioheat equation
      to quantify the temperature rise, and the effect of scattering is disregarded.
      The coefficient alphaeffec includes the scattering contribution as an additional
      absorption term and should allow us to make a better estimation of the thermal
      dose (TD), which is important for clinical applications. We simulated the bioheat
      equation with the source term considering alphaA or alphaeffec, and with heating
      provided by therapeutic ultrasound (1MHz, 2.0Wcm-2) for about 5.5min (temperature
      range 36-46 degrees C). Experimental data were obtained in similar heating
      conditions for a bovine muscle tissue (ex vivo) and temperature curves were
      measured for depths 7, 30, 35, 40 and 45mm. The TD values from the experimental
      temperature curves at each depth were compared with the numerical solution of the
      bioheat equation with the classical and corrected source terms. The highest
      percentual difference between simulated and experimental TD was 42.5% when
      assuming the classical alphaA, and 8.7% for the corrected alphaeffec. The results
      show that the effective absorption coefficient is a feasible parameter to improve
      the classical bioheat transfer model, especially for depths larger than the mean
      free propagation path.

PMID- 28753418
TI  - Comparison of cadmium absorption, translocation, subcellular distribution and
      chemical forms between two radish cultivars (Raphanus sativus L.).
AB  - Cadmium (Cd) absorption and accumulation vary greatly not only among plant
      species but also among cultivars within the same species. In order to better
      understand the mechanisms of Cd absorption, transportation and distribution, we
      examined the differences of Cd absorption, translocation, subcellular
      distribution and chemical forms between L19, a Cd-tolerant genotype, and H4, a Cd
      sensitive genotype, using kinetic analysis and soil culture experiment. Kinetic
      assays showed that the different Cd concentrations between the two cultivars
      might be ascribed to root absorption and translocation from root to shoot. The
      investigations of subcellular distribution and chemical forms verified that Cd
      concentrations of all subcellular fractions in H4 were all higher than in L19.
      Meanwhile, most of the Cd was associated with cell walls in the root of H4, but
      the Cd in the root of L19 and leaf of the two cultivars was mainly stored in
      soluble fraction, which could be one possible mechanism of tolerance to Cd
      toxicity. In addition, Cd fractions extracted by 1M NaCl and 2% HAC were
      predominant in root and leaf of both cultivars and the concentrations and
      proportions extracted by water and 80% ethanol in root and 1M NaCl in leaf were
      all higher in H4 than in L19. These results indicate that the Cd in H4 is more
      active than L19, which could be responsible for the sensitivity of H4 to Cd
      damage.

PMID- 28753419
TI  - Impacts of residual aluminum from aluminate flocculant on the morphological and
      physiological characteristics of Vallisneria natans and Hydrilla verticillata.
AB  - Aluminate is generally used as a flocculant in water and wastewater treatment
      processes, but the residual aluminum (Al) may have toxic effects on aquatic
      organisms when the concentration accumulates beyond a threshold level. The in
      situ and laboratory tests were conducted to evaluate the impact of residual Al on
      submerged macrophytes in West Lake, Hangzhou, China, which receives Al flocculant
      purified water diverted from the Qiantang River. The responses of Vallisneria
      natans and Hydrilla verticillata were investigated based on their morphological
      and physiological parameters in pot culture and aquarium simulation experiments.
      In the pot culture experiments, the biomass, seedling number, plant height,
      stolon number, stolon length, and root weight were significantly higher at a site
      located 150m from the inlet compared with those at a site located 15m from the
      inlet (P < 0.05), thereby indicating that the residual Al significantly inhibited
      the morphological development of V. natans and H. verticillata. The variations in
      the chlorophyll-a, protein, and malondialdehyde contents of the two species in
      both the pot culture and aquarium simulation experiments also demonstrated that
      the two submerged macrophytes were stressed by residual Al. V. natans and H.
      verticillata accumulated 0.052-0.227mg of Al per gram of plant biomass (fresh
      weight, mg/g FW) and 0.045-0.205mg Al/g FW in the in situ experiments,
      respectively, where the amounts of Al were significantly higher in the plants in
      the treatment aquaria during the laboratory experiments than those in the
      controls. These results may have important implications for the restoration of
      submerged macrophytes and ecological risk assessments in Al-exposed lakes. It is
      recommended that the Al salt concentration used for the control of lake
      eutrophication should be reduced to an appropriate level.

PMID- 28753420
TI  - Raphe Circuits on the Menu.
AB  - The dorsal raphe nucleus (DRN) is an important brain area for body-weight
      regulation. In this issue of Cell, Nectow et al. uncover cell-type-specific
      neural circuitry and pharmacology for appetite control within the DRN.

PMID- 28753421
TI  - Drugs, Bugs, and Cancer: Fusobacterium nucleatum Promotes Chemoresistance in
      Colorectal Cancer.
AB  - The tumor microenvironment has recently been shown to play decisive roles in
      chemotherapeutic response. In this issue of Cell, Yu et al. add to these findings
      by identifying the bacterium Fusobacterium nucleatum as a previously unrecognized
      chemoresistance mediator in colorectal cancer, thereby establishing the
      microbiota as a potential therapeutic target.

PMID- 28753422
TI  - How Ligands Illuminate GPCR Molecular Pharmacology.
AB  - G protein-coupled receptors (GPCRs), which are modulated by a variety of
      endogenous and synthetic ligands, represent the largest family of druggable
      targets in the human genome. Recent structural and molecular studies have both
      transformed and expanded classical concepts of receptor pharmacology and have
      begun to illuminate the distinct mechanisms by which structurally, chemically,
      and functionally diverse ligands modulate GPCR function. These molecular insights
      into ligand engagement and action have enabled new computational methods and
      accelerated the discovery of novel ligands and tool compounds, especially for
      understudied and orphan GPCRs. These advances promise to streamline the
      development of GPCR-targeted medications.

PMID- 28753423
TI  - Identification of a Brainstem Circuit Controlling Feeding.
AB  - Hunger, driven by negative energy balance, elicits the search for and consumption
      of food. While this response is in part mediated by neurons in the hypothalamus,
      the role of specific cell types in other brain regions is less well defined.
      Here, we show that neurons in the dorsal raphe nucleus, expressing vesicular
      transporters for GABA or glutamate (hereafter, DRNVgat and DRNVGLUT3 neurons),
      are reciprocally activated by changes in energy balance and that modulating their
      activity has opposite effects on feeding-DRNVgat neurons increase, whereas
      DRNVGLUT3 neurons suppress, food intake. Furthermore, modulation of these neurons
      in obese (ob/ob) mice suppresses food intake and body weight and normalizes
      locomotor activity. Finally, using molecular profiling, we identify druggable
      targets in these neurons and show that local infusion of agonists for specific
      receptors on these neurons has potent effects on feeding. These data establish
      the DRN as an important node controlling energy balance. PAPERCLIP.

PMID- 28753424
TI  - Alzheimer's-Causing Mutations Shift Abeta Length by Destabilizing gamma-Secretase
      Abetan Interactions.
AB  - Alzheimer's disease (AD)-linked mutations in Presenilins (PSEN) and the amyloid
      precursor protein (APP) lead to production of longer amyloidogenic Abeta
      peptides. The shift in Abeta length is fundamental to the disease; however, the
      underlying mechanism remains elusive. Here, we show that substrate shortening
      progressively destabilizes the consecutive enzyme-substrate (E-S) complexes that
      characterize the sequential gamma-secretase processing of APP. Remarkably,
      pathogenic PSEN or APP mutations further destabilize labile E-S complexes and
      thereby promote generation of longer Abeta peptides. Similarly, destabilization
      of wild-type E-S complexes by temperature, compounds, or detergent promotes
      release of amyloidogenic Abeta. In contrast, E-Abetan stabilizers increase gamma
      secretase processivity. Our work presents a unifying model for how PSEN or APP
      mutations enhance amyloidogenic Abeta production, suggests that environmental
      factors may increase AD risk, and provides the theoretical basis for the
      development of gamma-secretase/substrate stabilizing compounds for the prevention
      of AD.

PMID- 28753425
TI  - Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein
      Coupled Receptors.
AB  - G protein-coupled receptors (GPCRs) mediate diverse signaling in part through
      interaction with arrestins, whose binding promotes receptor internalization and
      signaling through G protein-independent pathways. High-affinity arrestin binding
      requires receptor phosphorylation, often at the receptor's C-terminal tail. Here,
      we report an X-ray free electron laser (XFEL) crystal structure of the rhodopsin
      arrestin complex, in which the phosphorylated C terminus of rhodopsin forms an
      extended intermolecular beta sheet with the N-terminal beta strands of arrestin.
      Phosphorylation was detected at rhodopsin C-terminal tail residues T336 and S338.
      These two phospho-residues, together with E341, form an extensive network of
      electrostatic interactions with three positively charged pockets in arrestin in a
      mode that resembles binding of the phosphorylated vasopressin-2 receptor tail to
      beta-arrestin-1. Based on these observations, we derived and validated a set of
      phosphorylation codes that serve as a common mechanism for phosphorylation
      dependent recruitment of arrestins by GPCRs.

PMID- 28753426
TI  - Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon
      Antiviral Activity.
AB  - Interferon-alpha (IFNalpha) signaling is essential for antiviral response via
      induction of IFN-stimulated genes (ISGs). Through a non-biased high-throughput
      RNAi screening of 711 known epigenetic modifiers in cellular models of IFNalpha
      mediated inhibition of HBV replication, we identified methyltransferase SETD2 as
      a critical amplifier of IFNalpha-mediated antiviral immunity. Conditional
      knockout mice with hepatocyte-specific deletion of Setd2 exhibit enhanced HBV
      infection. Mechanistically, SETD2 directly mediates STAT1 methylation on lysine
      525 via its methyltransferase activity, which reinforces IFN-activated STAT1
      phosphorylation and antiviral cellular response. In addition, SETD2 selectively
      catalyzes the tri-methylation of H3K36 on promoters of some ISGs such as ISG15,
      leading to gene activation. Our study identifies STAT1 methylation on K525
      catalyzed by the methyltransferase SETD2 as an essential signaling event for
      IFNalpha-dependent antiviral immunity and indicates potential of SETD2 in
      controlling viral infections.

PMID- 28753428
TI  - Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets
      Mutations to Active Genes.
AB  - Many processes can cause the same nucleotide change in a genome, making the
      identification of the mechanisms causing mutations a difficult challenge. Here,
      we show that clustered mutations provide a more precise fingerprint of mutagenic
      processes. Of nine clustered mutation signatures identified from >1,000 tumor
      genomes, three relate to variable APOBEC activity and three are associated with
      tobacco smoking. An additional signature matches the spectrum of translesion DNA
      polymerase eta (POLH). In lymphoid cells, these mutations target promoters,
      consistent with AID-initiated somatic hypermutation. In solid tumors, however,
      they are associated with UV exposure and alcohol consumption and target the
      H3K36me3 chromatin of active genes in a mismatch repair (MMR)-dependent manner.
      These regions normally have a low mutation rate because error-free MMR also
      targets H3K36me3 chromatin. Carcinogens and error-prone repair therefore
      redistribute mutations to the more important regions of the genome, contributing
      a substantial mutation load in many tumors, including driver mutations.

PMID- 28753427
TI  - A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of
      Endothelin-1 Gene Expression.
AB  - Genome-wide association studies (GWASs) implicate the PHACTR1 locus (6p24) in
      risk for five vascular diseases, including coronary artery disease, migraine
      headache, cervical artery dissection, fibromuscular dysplasia, and hypertension.
      Through genetic fine mapping, we prioritized rs9349379, a common SNP in the third
      intron of the PHACTR1 gene, as the putative causal variant. Epigenomic data from
      human tissue revealed an enhancer signature at rs9349379 exclusively in aorta,
      suggesting a regulatory function for this SNP in the vasculature. CRISPR-edited
      stem cell-derived endothelial cells demonstrate rs9349379 regulates expression of
      endothelin 1 (EDN1), a gene located 600 kb upstream of PHACTR1. The known
      physiologic effects of EDN1 on the vasculature may explain the pattern of risk
      for the five associated diseases. Overall, these data illustrate the integration
      of genetic, phenotypic, and epigenetic analysis to identify the biologic
      mechanism by which a common, non-coding variant can distally regulate a gene and
      contribute to the pathogenesis of multiple vascular diseases.

PMID- 28753429
TI  - Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by
      Modulating Autophagy.
AB  - Gut microbiota are linked to chronic inflammation and carcinogenesis.
      Chemotherapy failure is the major cause of recurrence and poor prognosis in
      colorectal cancer patients. Here, we investigated the contribution of gut
      microbiota to chemoresistance in patients with colorectal cancer. We found that
      Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in
      patients with recurrence post chemotherapy, and was associated with patient
      clinicopathological characterisitcs. Furthermore, our bioinformatic and
      functional studies demonstrated that F. nucleatum promoted colorectal cancer
      resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88
      innate immune signaling and specific microRNAs to activate the autophagy pathway
      and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum
      orchestrates a molecular network of the Toll-like receptor, microRNAs, and
      autophagy to clinically, biologically, and mechanistically control colorectal
      cancer chemoresistance. Measuring and targeting F. nucleatum and its associated
      pathway will yield valuable insight into clinical management and may ameliorate
      colorectal cancer patient outcomes.

PMID- 28753430
TI  - Defining a Cancer Dependency Map.
AB  - Most human epithelial tumors harbor numerous alterations, making it difficult to
      predict which genes are required for tumor survival. To systematically identify
      cancer dependencies, we analyzed 501 genome-scale loss-of-function screens
      performed in diverse human cancer cell lines. We developed DEMETER, an analytical
      framework that segregates on- from off-target effects of RNAi. 769 genes were
      differentially required in subsets of these cell lines at a threshold of six SDs
      from the mean. We found predictive models for 426 dependencies (55%) by nonlinear
      regression modeling considering 66,646 molecular features. Many dependencies fall
      into a limited number of classes, and unexpectedly, in 82% of models, the top
      biomarkers were expression based. We demonstrated the basis behind one such
      predictive model linking hypermethylation of the UBB ubiquitin gene to a
      dependency on UBC. Together, these observations provide a foundation for a cancer
      dependency map that facilitates the prioritization of therapeutic targets.

PMID- 28753432
TI  - SnapShot: Channel Gating Mechanisms.
AB  - Ion channel families are broadly classified into three types according to their
      major mechanisms of activation. This SnapShot highlights features of these three
      classes and conveys general modes of channel regulation. To view this SnapShot,
      open or download the PDF.

PMID- 28753433
TI  - Effect of kisspeptin-10, LH and hCG on serum testosterone concentrations in
      stallions, donkeys and mules.
AB  - This study was conducted to determine the response of serum testosterone (T) in
      male equines (stallions, donkeys and mules) after administering intravenous doses
      of kisspeptin-10 (KP-10), human chorionic gonadotropin (hCG) and luteinizing
      hormone (LH) and saline as a control. The animals were divided into four groups
      of three each: Group I, 3 ml of 0.95% saline; Group II, 50 MUg KP-10; Group III,
      2500 IU hCG and group IV, 400 MUg LH. The administration of KP-10 and hCG to
      stallions resulted in a significant increase in serum T concentration at 240 min;
      whereas it was significantly higher at 30, 60, 120, and 240 min with LH treatment
      as compared to pre-dose concentrations. Both KP-10 and hCG significantly elevated
      the T concentrations in donkeys at 120 and 240 min, respectively; whereas it was
      significantly higher at 60, 120, and 240 min with LH treatment as compared to pre
      dose concentration. Both KP-10 and LH elevated T in donkeys at 240 min as
      compared to the control and hCG concentrations. After 120 and 240 min, T
      concentrations in mules were higher (p < 0.05) with administration of KP-10, hCG
      and LH as compared to the control. In conclusion, the administration of KP-10,
      hCG and LH elevate the serum T concentration in normal male equines. It is
      suggested that KP-10 may be useful in situations where an increase in T is
      desired. Further work is required to determine the effect of KP-10 on T in male
      equids with reproductive abnormalities before it can be used in clinical
      situations.

PMID- 28753431
TI  - Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal
      Relationships Uncovered by Large-Scale, Deep RNAi Screening.
AB  - Elucidation of the mutational landscape of human cancer has progressed rapidly
      and been accompanied by the development of therapeutics targeting mutant
      oncogenes. However, a comprehensive mapping of cancer dependencies has lagged
      behind and the discovery of therapeutic targets for counteracting tumor
      suppressor gene loss is needed. To identify vulnerabilities relevant to specific
      cancer subtypes, we conducted a large-scale RNAi screen in which viability
      effects of mRNA knockdown were assessed for 7,837 genes using an average of 20
      shRNAs per gene in 398 cancer cell lines. We describe findings of this screen,
      outlining the classes of cancer dependency genes and their relationships to
      genetic, expression, and lineage features. In addition, we describe robust gene
      interaction networks recapitulating both protein complexes and functional
      cooperation among complexes and pathways. This dataset along with a web portal is
      provided to the community to assist in the discovery and translation of new
      therapeutic approaches for cancer.

PMID- 28753434
TI  - Morphological, histological and molecular investigations on canine uterine tissue
      after ovariectomy.
AB  - In the present study, we investigated the course of atrophy in canine uterine
      tissue and the expression of estrogen receptors (ER) and progesterone receptors
      (PR) within 6 months after ovariectomy (OE). In nine primipar bitches of
      different breeds, bilateral OE and removal of one horn was performed. Six months
      after surgery, the remaining uterine tissue was removed. The tissue was examined
      for signs of inflammation and proliferation, and for expression of ER, PR and
      Ki67 by means of immunohistochemistry (IHC); furthermore transcription of
      vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF
      beta), epithelial growth factor (EGF), platelet activating factor (PAF), tumor
      necrosis factor alpha (TNFalpha), and their specific receptors was determined by
      means of RT-qPCR. Serum concentrations of estrogen and progesterone were measured
      immediately before the first and second operation. Six month after OE, no
      inflammation was seen in any uterine tissue, the thickness of the stump was
      decreased in most bitches. Protein expression of Ki67 revealed high individual
      differences after the second operation. Concentration of both hormones was not
      significantly changed, the estrogen concentration always revealed high individual
      differences. The expression of ER was significantly decreased in stromal and
      smooth muscle cells of the uterine tissue (p < 0.01), and the expression of PR in
      stromal cells only (p < 0.05). The gene expression of growth factors did not
      change significantly between first and second operation. We conclude that
      complete atrophy did not occur within 6 months after OE, instead, a high
      percentage of uterine cells still expressed ER and PR, rendering the stump
      susceptible to hormone treatments.

PMID- 28753435
TI  - The contribution of spatial ability to mathematics achievement in middle
      childhood.
AB  - Strong spatial skills are associated with success in science, technology,
      engineering, and mathematics (STEM) domains. Although there is convincing
      evidence that spatial skills are a reliable predictor of mathematical achievement
      in preschool children and in university students, there is a lack of research
      exploring associations between spatial and mathematics achievement during the
      primary school years. To address this question, this study explored associations
      between mathematics and spatial skills in children aged 5 and 7years. The study
      sample included 12,099 children who participated in both Wave 3 (mean age=5; 02
      [years; months]) and Wave 4 (mean age=7; 03) of the Millennium Cohort Study.
      Measures included a standardised assessment of mathematics and the Pattern
      Construction subscale of the British Ability Scales II to assess intrinsic
      dynamic spatial skills. Spatial skills at 5 and 7years of age explained a
      significant 8.8% of the variation in mathematics achievement at 7years, above
      that explained by other predictors of mathematics, including gender,
      socioeconomic status, ethnicity, and language skills. This percentage increased
      to 22.6% without adjustment for language skills. This study expands previous
      findings by using a large-scale longitudinal sample of primary school children, a
      population that has been largely omitted from previous research exploring
      associations between spatial ability and mathematics achievement. The finding
      that early and concurrent spatial skills contribute to mathematics achievement at
      7years of age highlights the potential of spatial skills as a novel target in the
      design of mathematics interventions for children in this age range.

PMID- 28753436
TI  - Relations between theory of mind and executive function in middle childhood: A
      short-term longitudinal study.
AB  - Studies with preschool children have shown significant links between children's
      executive function (EF) and theory of mind (ToM), but few studies have examined
      these associations in primary school children. To address this gap, we designed a
      three-wave cross-lagged longitudinal study in which we followed a group of 113
      children (61 boys) across three time points from age 9.5-10.5years (mean age at
      Time 1=112.3months, SD=4.18; mean age at Time 2=118.3months, SD=4.15; mean age at
      Time 3=124.7months, SD=4.06). At each time point, we measured EF (working memory
      and inhibitory control), ToM, and language. Our analyses showed (a) moderate rank
      order stability of individual differences in both EF and ToM and (b) growth in
      ToM task performance across time. Cross-lagged longitudinal analyses revealed an
      asymmetric developmental relation between ToM and working memory. Early working
      memory predicted later ToM but not vice versa. Our results suggest a specific
      role for working memory in the ongoing development of ToM in middle childhood.

PMID- 28753437
TI  - Developing control over the execution of scripts: The role of maintained
      hierarchical goal representations.
AB  - The execution of a script often requires detecting and resolving conflict with a
      goal, particularly in nonroutine situations. To take the example of taking a bus
      daily to work, if someone's usual bus is delayed and a bus for another
      destination comes first, the person must inhibit taking it and wait for the usual
      one. Young children can gradually acquire the ability to control the execution of
      scripts in such nonroutine situations, but few studies have explored the control
      process involved. In two experiments, we investigated the role of developments in
      the maintenance of hierarchical goal representations and in executive functions.
      We measured the ability to control the execution of scripts using a task in which
      children helped a doll select items to wear; clothing options were presented in
      an unexpected order in the nonroutine situations. The younger children (4-year
      olds) could not flexibly control their execution of scripts in nonroutine
      situations, although they could exogenously detect and resolve conflict if they
      were prompted to maintain a subgoal. The older children (5-year-olds)
      endogenously controlled script execution based on a main goal, whereas subgoal
      maintenance led them to rigidly control their performance. In addition,
      children's inhibition abilities were associated with their control of script
      execution. These findings indicate that the development of the control process
      underlying the execution of scripts in nonroutine situations is partially
      dependent on the ability to maintain hierarchical goal representations.

PMID- 28753439
TI  - Quo vadis: tracing the fate of neural crest cells.
AB  - The neural crest is a transient structure in vertebrate embryos that produces
      migratory cells with an astonishing developmental potential. While neural crest
      fate maps have originally been established through interspecies transplantation
      assays, dye labeling, and retroviral infection, more recent methods rely on
      approaches involving transgenesis and genome editing. These technologies allowed
      the identification of minor neural crest-derived cell populations in tissues of
      non-neural crest origin. Furthermore, in vivo multipotency at the single cell
      level and stage-dependent fate acquisitions were demonstrated using genetic
      technologies. Finally, recent reports indicate that neural crest-derived cells
      become activated in response to injury to secrete factors supporting tissue
      repair. Thus, neural crest-derived cells apparently contribute to tissue
      formation and regeneration by cell autonomous and non-autonomous mechanisms.

PMID- 28753438
TI  - Bilingual language intrusions and other speech errors in Alzheimer's disease.
AB  - The current study investigated how Alzheimer's disease (AD) affects production of
      speech errors in reading-aloud. Twelve Spanish-English bilinguals with AD and 19
      matched controls read-aloud 8 paragraphs in four conditions (a) English-only, (b)
      Spanish-only, (c) English-mixed (mostly English with 6 Spanish words), and (d)
      Spanish-mixed (mostly Spanish with 6 English words). Reading elicited language
      intrusions (e.g., saying la instead of the), and several types of within-language
      errors (e.g., saying their instead of the). Patients produced more intrusions
      (and self-corrected less often) than controls, particularly when reading non
      dominant language paragraphs with switches into the dominant language. Patients
      also produced more within-language errors than controls, but differences between
      groups for these were not consistently larger with dominant versus non-dominant
      language targets. These results illustrate the potential utility of speech errors
      for diagnosis of AD, suggest a variety of linguistic and executive control
      impairments in AD, and reveal multiple cognitive mechanisms needed to mix
      languages fluently. The observed pattern of deficits, and unique sensitivity of
      intrusions to AD in bilinguals, suggests intact ability to select a default
      language with contextual support, to rapidly translate and switch languages in
      production of connected speech, but impaired ability to monitor language
      membership while regulating inhibitory control.

PMID- 28753440
TI  - Cis-drivers and trans-drivers of bovine leukemia virus oncogenesis.
AB  - The bovine leukemia virus (BLV) is a retrovirus inducing an asymptomatic and
      persistent infection in ruminants and leading in a minority of cases to the
      accumulation of B-lymphocytes (lymphocytosis, leukemia or lymphoma). Although the
      mechanisms of oncogenesis are still largely unknown, there is clear experimental
      evidence showing that BLV infection drastically modifies the pattern of gene
      expression of the host cell. This alteration of the transcriptome in infected B
      lymphocytes results first, from a direct activity of viral proteins (i.e.
      transactivation of gene promoters, protein-protein interactions), second, from
      insertional mutagenesis by proviral integration (cis-activation) and third, from
      gene silencing by microRNAs. Expression of viral proteins stimulates a vigorous
      immune response that indirectly modifies gene transcription in other cell types
      (e.g. cytotoxic T-cells, auxiliary T-cells, macrophages). In principle,
      insertional mutagenesis and microRNA-associated RNA interference can modify the
      cell fate without inducing an antiviral immunity. Despite a tight control by the
      immune response, the permanent attempts of the virus to replicate ultimately
      induce mutations in the infected cell. Accumulation of these genomic lesions and
      Darwinian selection of tumor clones are predicted to lead to cancer.

PMID- 28753441
TI  - RNAi-mediated resistance to viruses: a critical assessment of methodologies.
AB  - In plants, RNA interference (RNAi)-based antiviral defense is mediated by
      multigenic families of Dicer-like enzymes generating small interfering (si)RNAs
      from double-stranded RNA (dsRNA) produced during replication and/or transcription
      of RNA and DNA viruses, and Argonaute enzymes binding viral siRNAs and targeting
      viral RNA and DNA for siRNA-directed posttranscriptional and transcriptional
      silencing. Successful viruses are able to suppress or evade the production or
      action of viral siRNAs. In antiviral biotech approaches based on RNAi, transgenic
      expression or non-transgenic delivery of dsRNA cognate to a target virus pre
      activates or boosts the natural plant antiviral defenses. Design of more
      effective antiviral RNAi strategies requires better understanding of viral siRNA
      biogenesis and viral anti-silencing strategies in virus-infected plants.

PMID- 28753442
TI  - The Antitumor Activity of IMGN529, a CD37-Targeting Antibody-Drug Conjugate, Is
      Potentiated by Rituximab in Non-Hodgkin Lymphoma Models.
AB  - Naratuximab emtansine (IMGN529) is an investigational antibody-drug conjugate
      consisting of a CD37-targeting antibody conjugated to the maytansine-derived
      microtuble disruptor, DM1. IMGN529 has shown promising preclinical and clinical
      activity in non-Hodgkin lymphoma, including diffuse large B-cell lymphoma
      (DLBCL). Due to the aggressive nature of the disease, DLBCL is often treated with
      combination therapies to maximize clinical outcomes; therefore, we investigated
      the potential of combining IMGN529 with both standard-of-care and emerging
      therapies against multiple oncology-relevant targets and pathways. The strongest
      enhancement in potency was seen with anti-CD20 antibodies, including rituximab.
      The combination of IMGN529 and rituximab was more potent than either agent alone,
      and this combinatorial benefit was associated with increased apoptotic induction
      and cell death. Additional studies revealed that rituximab treatment increased
      the internalization and degradation of the CD37-targeting antibody moiety of
      IMGN529. The combination of IMGN529 and rituximab was highly efficacious in
      multiple xenograft models, with superior antitumor efficacy seen compared to
      either agent alone or treatment with R-CHOP therapy. These findings suggest a
      novel mechanism whereby the potency of IMGN529 can be enhanced by CD20 binding,
      which results in the increased internalization and degradation of IMGN529 leading
      to the generation of greater amounts of cytotoxic catabolite. Overall, these data
      provide a biological rationale for the enhanced activity of IMGN529 in
      combination with rituximab and support the ongoing clinical evaluation of IMGN529
      in combination with rituximab in patients with relapsed and/or refractory DLBCL.

PMID- 28753443
TI  - Activity in part of the neural correlates of consciousness reflects integration.
AB  - Integration is commonly viewed as a key process for generating conscious
      experiences. Accordingly, there should be increased activity within the neural
      correlates of consciousness when demands on integration increase. We used fMRI
      and "informational masking" to isolate the neural correlates of consciousness and
      measured how the associated brain activity changed as a function of required
      integration. Integration was manipulated by comparing the experience of hearing
      simple reoccurring tones to hearing harmonic tone triplets. The neural correlates
      of auditory consciousness included superior temporal gyrus, lateral and medial
      frontal regions, cerebellum, and also parietal cortex. Critically, only activity
      in left parietal cortex increased significantly as a function of increasing
      demands on integration. We conclude that integration can explain part of the
      neural activity associated with the generation conscious experiences, but that
      much of associated brain activity apparently reflects other processes.

PMID- 28753444
TI  - Effect of matrix stiffness on the proliferation and differentiation of umbilical
      cord mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are a compatible cellular alternative for
      regenerative medicine and tissue engineering because of their powerful
      multipotency. Matrix stiffness plays a profound role on stem cell behavior.
      Nevertheless, the effect of matrix stiffness on umbilical cordmesenchymal stem
      cells (UC-MSCs) remains unexplored. To conduct an in-depth exploration, we
      cultured UC-MSCs on different stiffness (Young's modulus: 13-16, 35-38, 48-53,
      and 62-68 kPa) polyacrylamide gels coated with fibronectin. We found that the
      proliferation and adhesion of UC-MSCs varied when cultured on the different
      matrices, and the spreading capacity was stronger as the stiffness increased
      (*P<0.05). Real-time quantitative PCR results showed that the soft matrix
      promoted adipogenic differentiation, with higher expression levels of adipocytic
      markers like PPARgamma and C/EBPalpha (*P<0.05). In contrast, cells tended to
      differentiate into muscle when cultured on the 48-53 kPa matrix, which was
      validated by increased expression of myogenic makers like desminand MOYG
      (*P<0.05). Moreover, increased expression of osteoblastic makers (*P<0.05), such
      as ALP, collagen type I, osteocalcin, and Runx2, confirmed that cells
      differentiated into bone on the high-stiffness matrix.

PMID- 28753445
TI  - Decomposition approach to the stability of recurrent neural networks with
      asynchronous time delays in quaternion field.
AB  - In this paper, the global exponential stability for recurrent neural networks
      (QVNNs) with asynchronous time delays is investigated in quaternion field. Due to
      the non-commutativity of quaternion multiplication resulting from Hamilton rules:
      ij=-ji=k, jk=-kj=i, ki=-ik=j, ijk=i2=j2=k2=-1, the QVNN is decomposed into four
      real-valued systems, which are studied separately. The exponential convergence is
      proved directly accompanied with the existence and uniqueness of the equilibrium
      point to the consider systems. Combining with the generalized infinity-norm and
      Cauchy convergence property in the quaternion field, some sufficient conditions
      to guarantee the stability are established without using any Lyapunov-Krasovskii
      functional and linear matrix inequality. Finally, a numerical example is given to
      demonstrate the effectiveness of the results.

PMID- 28753446
TI  - Global Mittag-Leffler stability analysis of fractional-order impulsive neural
      networks with one-side Lipschitz condition.
AB  - This paper is concerned with the stability analysis issue of fractional-order
      impulsive neural networks. Under the one-side Lipschitz condition or the linear
      growth condition of activation function, the existence of solution is analyzed
      respectively. In addition, the existence, uniqueness and global Mittag-Leffler
      stability of equilibrium point of the fractional-order impulsive neural networks
      with one-side Lipschitz condition are investigated by the means of contraction
      mapping principle and Lyapunov direct method. Finally, an example with numerical
      simulation is given to illustrate the validity and feasibility of the proposed
      results.

PMID- 28753447
TI  - Stability and synchronization of fractional-order memristive neural networks with
      multiple delays.
AB  - The paper presents theoretical results on the global asymptotic stability and
      synchronization of a class of fractional-order memristor-based neural networks
      (FMNN) with multiple delays. First, the asymptotic stability of fractional-order
      (FO) linear systems with single or multiple delays is discussed. Delay
      independent stability criteria for the two types of systems are established by
      using the maximum modulus principle and the spectral radii of matrices. Second,
      new testable algebraic criteria for ensuring the existence and global asymptotic
      stability of the system equilibrium point are obtained by employing the
      Kakutani's fixed point theorem of set-valued maps, the comparison theorem, and
      the stability criterion for FO linear systems with multiple delays. Third, the
      synchronization criterion for FMNN is presented based on the linear error
      feedback control. Finally, numerical examples are given demonstrating the
      effectiveness of the proposed results.

PMID- 28753448
TI  - Negativity bias and instability in spontaneous and deliberate evaluations of
      others: The role of borderline personality features.
AB  - This study tested the hypotheses that borderline personality (BP) features are
      characterized by a negativity bias and instability in spontaneous and deliberate
      evaluations of others. Undergraduate women (N = 204) watched two movie clips
      depicting either positive or negative conjugal interactions. Spontaneous and
      deliberate evaluations of the male character were assessed after each clip with
      an Evaluative Priming Task and a self-report measure, respectively. Participants
      with high BP features showed unstable spontaneous evaluations. Results revealed a
      non-significant trend toward more negative spontaneous evaluations after the
      negative clip and less positive and more negative deliberate evaluations after
      watching the positive clip first relative to participants with low BP features.
      These results provide preliminary evidence that impression formation in
      borderline personality may be characterized by negative and unstable evaluations
      that are shaped at least in part at earlier processing stages.

PMID- 28753449
TI  - Attentional avoidance of threats in obsessive compulsive disorder: An event
      related potential study.
AB  - The neural mechanism underlying attentional bias in OCD (Obsessive-Compulsive
      Disorder) remains unclear. The goal of this study was to examine and compare the
      time course and the event related potential (ERP) components in OCD patients and
      healthy controls (HC) to reveal the complex brain activation pattern associated
      with attentional bias in OCD. The behavioural and electroencephalogram (EEG) data
      were recorded while the participants performed an emotional Stroop task. Compared
      to HC, the individuals with OCD exhibited slower response time, prolonged N1
      latency and larger N1 and P2 amplitudes across different emotional words. In
      addition, we discovered that the OCD group showed an enlarged N1 component to OCD
      related threat words compared to neutral words. Moreover, the OCD group had
      decreased P3 and later positive potential (LPP) amplitudes towards all types of
      words compared to the HC group. More importantly, the OCD group manifested
      smaller LPP amplitude to threat words compared to the HC group. Our findings
      suggest that OCD individuals may excessively direct their attention away from the
      threat at the late processing stage, probably due to the intensive processing or
      overestimation of the stimuli in the early automatic processing stage.

PMID- 28753450
TI  - A novel cardiovascular death prediction model for Chinese individuals: A
      prospective cohort study of 381,963 study participants.
AB  - BACKGROUND AND AIMS: We aimed at developing a novel risk prediction model for
      death from cardiovascular disease (CVD) for Chinese individuals, based upon a
      large cohort from Taiwan. METHODS: This Chinese cohort came from Taiwan, with
      381,963 individuals free from CVD, recruited from a private health surveillance
      program. With a median follow-up of 8.8 years, 1894 CVD deaths out of a total of
      10,829 deaths were identified by linking cohort ID with the National Death File.
      RESULTS: A novel CVD death risk prediction model for Chinese individuals was
      established from this cohort. An increase in the resting heart rate was the
      statistically independent predictor in this model. The discriminatory accuracy
      was measured by generating the receiver operating characteristic (ROC) curve, and
      the area under the ROC curve was 0.913 (95% CI = 0.907 to 0.920). CONCLUSIONS: A
      novel cardiovascular death prediction model with high predictability for Chinese
      individuals was demonstrated in the present study.

PMID- 28753451
TI  - Major depression: An under reported neuropsychiatric manifestation of Mixed
      Connective Tissue Disease.

PMID- 28753452
TI  - Psychometric properties of the Chinese version of the child and adolescent
      factors inventory (CAFI-C).
AB  - The Child and Adolescent Factors Inventory (CAFI) is a parent-report measure that
      assesses type and severity of impairments experienced by children and youth with
      a range of disabling conditions. The CAFI was translated from English into
      Traditional Chinese (CAFI-C) and has been used in the Disability Evaluation
      System (DES) in Taiwan. The aim of this study was to validate the use of the CAFI
      C in the DES. Participants included 18,119 children and youth with disabilities
      between the ages of 6.0-17.9 (Mean=11.6; SD=3.46). The factor structure, internal
      consistency, convergent validity, and discriminant (known groups) validity were
      examined. The results indicated that the CAFI-C had a two-factor structure
      (Mental/speech and Physical/sensory impairment) that explained 54.3% of the
      variance, and had adequate internal consistency (alpha=0.80-0.90). Children and
      youth with higher CAFI-C scores had significantly more participation restrictions
      and environment barriers. CAFI-C scores were significantly different among
      children and youth with different disability types and of four severity levels
      (mild, moderate, severe, and profound) rated by physicians. These findings
      support the internal consistency and validity of the CAFI-C for assessing type
      and severity of impairment in children and youth with disabilities in Chinese
      speaking population.

PMID- 28753453
TI  - MiR-136 controls neurocytes apoptosis by regulating Tissue Inhibitor of
      Metalloproteinases-3 in spinal cord ischemic injury.
AB  - BACKGROUND: Spinal cord ischemia is a serious injury that threatens human health
      and life. Furthermore, it was widely accepted that miR-136 was mediated in the
      spinal injury, while whether it regulated neurocytes apoptosis in I/R-induced
      spinal cord injury remains unclear. METHODS: Spinal cord ischemia injury (SCII)
      rats were induced by clamping the nontraumatic vascular clip on the abdominal
      aorta. Real-time PCR was conducted to determine the mRNA expression, and western
      blot was carried out to measure protein expression. TUNEL assay was used to
      measure cell apoptosis. RESULTS: MiR-136 was up-regulated, while Tissue Inhibitor
      of Metalloproteinases-3 (TIMP3) was down-regulated in both SCII rats and hypoxic
      neurocytes. MiR-136 overexpression protected neurocytes against injury that
      induced by hypoxia. TIMP3 was the target gene of miR-136. Hypoxia supplementation
      decreased the expression of miR-136, promoted TIMP3 expression, and urged cell
      apoptosis, cells transfected with miR-136 mimic reversed the effect that induced
      by hypoxia, while cells co-transfected with pcDNA-TIMP3 abolished the results
      that induced by overexpressed miR-136. CONCLUSION: MiR-136 regulated neurocytes
      apoptosis of SCII by mediating TIMP3.

PMID- 28753454
TI  - Long noncoding RNA PCAT1 regulates extrahepatic cholangiocarcinoma progression
      via the Wnt/beta-catenin-signaling pathway.
AB  - Extrahepatic cholangiocarcinoma (ECC) is a deadly disease that often responds
      poorly to conventional chemotherapy or radiotherapy. Long noncoding RNAs
      (lncRNAs) play important roles in human cancers, including ECC, and recent
      studies indicated that the lncRNA prostate cancer-associated transcript 1 (non
      protein coding) (PCAT1) is involved in multiple cancers. However, the role of
      PCAT1 in ECC is unclear. Previously, we showed that PCAT1 is up-regulated in both
      ECC tissue samples and cell lines. Here, we showed that downregulation of PCAT1
      following transfection with silencing RNA reduced ECC cell growth and increased
      cell apoptosis. Additionally, PCAT1 suppression inhibited ECC cell migration and
      invasion as determined by transwell assay. Furthermore, we determined that PCAT1
      is a competing endogenous for microRNA (miR)-122, with bioinformatics analysis
      and luciferase-reporter assay results demonstrating that PCAT1 regulated WNT1
      expression via miR-122. Moreover, PCAT1 downregulation increased levels of
      glycogen synthase kinase 3beta and significantly decreased beta-catenin levels in
      whole cell lysates and nuclear fractions, indicating that PCAT1 silencing
      inhibited the Wnt/beta-catenin-signaling pathway. We also observed that exogenous
      expression of WNT1 reversed PCAT1-silencing-induced inhibition of ECC cell growth
      inhibition. These results indicated that PCAT1 silencing inhibited ECC
      progression by reducing Wnt/beta-catenin signaling through miR-122 repression and
      WNT1 expression. Our findings revealed an important role of PCAT1 in ECC and
      suggested that PCAT1 might be a potential ECC-related therapeutic target.

PMID- 28753455
TI  - Diallyl trisulfide induces apoptosis and mitotic arrest in AGS human gastric
      carcinoma cells through reactive oxygen species-mediated activation of AMP
      activated protein kinase.
AB  - Diallyl trisulfide (DATS), one of the principal constituents of garlic oil, is a
      kind of organosulfur compound with high anti-cancer activity. Although inhibition
      of cancer cell proliferation by DATS is known to be associated with the induction
      of apoptosis and cell cycle arrest related to reactive oxygen species (ROS)
      production, it is still necessary to study the detailed mechanisms. In this
      study, we investigated the role of ROS on the activation of AMP-activated protein
      kinase (AMPK) in DATS-induced apoptosis and cell cycle arrest in AGS human
      gastric carcinoma cells. The results of the present study indicate that DATS
      inhibited proliferation of AGS cells by promoting apoptosis, and accumulating
      cellular portion of G2/M phase via the induction of cyclin B1 and cyclin
      dependent kinase p21(WAF1/CIP1). The phosphorylation of histone H3 was also
      markedly increased following treatment with DATS, revealing that DATS stimulated
      a mitotic arrest, not the G2 phase. Furthermore, we found that DATS concurrently
      induced phosphorylation of AMPK; however, chemical inhibition of AMPK by compound
      C, an AMPK inhibitor, significantly blocked apoptosis induced by DATS, suggesting
      that DATS induces cytotoxicity of AGS cells through the AMPK-dependent pathway.
      Moreover, DATS provoked intracellular ROS generation and the loss of
      mitochondrial membrane potential, and in particular, when ROS production was
      blocked by antioxidant N-acety-l-cysteine, both AMPK activation and growth
      inhibition by DATS were completely abolished. Collectively, these findings
      suggest that DATS inhibited growth of AGS cells, which was mediated by complex
      interplay between cellular mechanisms governing redox homeostasis, apoptosis, and
      cell cycle arrest, through a ROS-dependent activation of AMPK pathway.

PMID- 28753456
TI  - Synaptic damage underlies EEG abnormalities in postanoxic encephalopathy: A
      computational study.
AB  - OBJECTIVE: In postanoxic coma, EEG patterns indicate the severity of
      encephalopathy and typically evolve in time. We aim to improve the understanding
      of pathophysiological mechanisms underlying these EEG abnormalities. METHODS: We
      used a mean field model comprising excitatory and inhibitory neurons, local
      synaptic connections, and input from thalamic afferents. Anoxic damage is modeled
      as aggravated short-term synaptic depression, with gradual recovery over many
      hours. Additionally, excitatory neurotransmission is potentiated, scaling with
      the severity of anoxic encephalopathy. Simulations were compared with continuous
      EEG recordings of 155 comatose patients after cardiac arrest. RESULTS: The
      simulations agree well with six common categories of EEG rhythms in postanoxic
      encephalopathy, including typical transitions in time. Plausible results were
      only obtained if excitatory synapses were more severely affected by short-term
      synaptic depression than inhibitory synapses. CONCLUSIONS: In postanoxic
      encephalopathy, the evolution of EEG patterns presumably results from gradual
      improvement of complete synaptic failure, where excitatory synapses are more
      severely affected than inhibitory synapses. The range of EEG patterns depends on
      the excitation-inhibition imbalance, probably resulting from long-term
      potentiation of excitatory neurotransmission. SIGNIFICANCE: Our study is the
      first to relate microscopic synaptic dynamics in anoxic brain injury to both
      typical EEG observations and their evolution in time.

PMID- 28753457
TI  - A nanoparticle-based method for culture-free bacterial DNA enrichment from whole
      blood.
AB  - Point-of-care (POC) diagnostics are one of the quick and sensitive detection
      approaches used in current clinical applications, but always face a performance
      tradeoff between time-to-result and assay sensitivity. One critical setting where
      these limitations are evident is the detection of sepsis, where 6-10mL of whole
      blood may contain as little as one bacterial colony forming unit (cfu). The large
      sample volume, complex nature of the sample and low analyte concentration
      necessitates signal enhancement using culture-based or molecular amplification
      techniques. In the time-critical diagnosis of sepsis, waiting for up to 24h to
      produce sufficient DNA for analysis is not possible. As a consequence, there is a
      need for integrated sample preparation methods that could enable shorter
      detection times, whilst maintaining high analytical performance. We report the
      development of a culture-free bacterial enrichment method to concentrate bacteria
      from whole blood in less than 3h. The method relies on triple-enrichment steps to
      magnetically concentrate bacterial cells and their DNA with a 500-fold reduction
      in sample volume (from 10 to 0.02mL). Using this sample preparation method,
      sensitive qPCR detection of the extracted S. aureus bacterial DNA was achieved
      with a detection limit of 5+/-0.58cfu/mL within a total elapsed time of 4h; much
      faster than conventional culture-based approaches. The method could be fully
      automated for integration into clinical practice for point-of-care or molecular
      detection of bacterial DNA from whole blood.

PMID- 28753458
TI  - Alteration of rhythmic unimanual tapping and anti-phase bimanual coordination in
      Alzheimer's disease: A sign of inter-hemispheric disconnection?
AB  - Little attention is paid to motor control in Alzheimer's disease (AD) although it
      is a relevant sign of central nervous system integrity and functioning. In
      particular, unimanual and bimanual tapping is a relevant paradigm because it
      requires intra- and inter-hemispheric transfer (IHT). Previous results indicate
      that both unimanual and anti-phase tapping requires more IHT than in-phase
      tapping, especially produced without external stimulation. The aim of the present
      study was to test the production of unimanual, bimanual in-phase and anti-phase
      tapping with a synchronization-continuation paradigm with and without visual
      stimulation in AD patients (N=9) and control participants (N=12). In accordance
      with our hypothesis, these results suggest that unimanual and anti-phase tapping
      is more altered in AD than in control participants. Moreover, performance is
      globally more variable in the AD group. These alterations are discussed in terms
      of possible IHT modulation, in line with functional and structural findings in
      AD, revealing changes in the connectivity of brain regions across hemispheres and
      white matter damage.

PMID- 28753459
TI  - Design, synthesis, in vitro Evaluation and docking studies on dihydropyrimidine
      based urease inhibitors.
AB  - In our previous report, we have identified 3,4-dihydropyrimidine scaffold as
      promising class of urease inhibitor in a structure based virtual screen (SBVS)
      experiment. In present study, we attempted to optimize the scaffold by varying C
      5 substituent. The elongation of the C-5 chain was achieved by the reaction of C
      5 ester with hydrazine leading to C-5 carbohydrazides which were further used as
      building blocks for the synthesis of fifteen new compounds having diverse
      moieties. A significantly higher in vitro urease inhibitory activity with IC50
      values in submicromolar range was observed for semithiocarbazide derivatives (4a
      c, 0.58-0.79uM) and isatin Schiff base derivative 5a (0.23uM). Docking analysis
      suggests that the synthesized compounds were anchored well in the catalytic site
      and extending to the entrance of binding pocket and thus restrict the mobility of
      the flap by interacting with its key amino acid residues. The overall results of
      urease inhibition have shown that these compounds can be further optimized and
      developed as lead urease inhibitors.

PMID- 28753460
TI  - ESCRT-dependent degradation of ubiquitylated plasma membrane proteins in plants.
AB  - To control the abundance of plasma membrane receptors and transporters is crucial
      for proper perception and response to extracellular signals from surrounding
      cells and the environment. Posttranslational modification of plasma membrane
      proteins, especially ubiquitin conjugation or ubiquitylation, is key for the
      determination of stability for many transmembrane proteins localized on the cell
      surface. The targeted degradation is ensured by a complex network of proteins
      among which the endosomal sorting complex required for transport (ESCRT) plays a
      central role. This review focuses on progresses made in recent years on the
      understanding of the function of the ESCRT machinery in the degradation of
      ubiquitylated plasma membrane proteins in plants.

PMID- 28753461
TI  - The predictive effect of empathy and social norms on adolescents' implicit and
      explicit stigma responses.
AB  - Research indicates that adolescents who experience mental health difficulties are
      frequently stigmatised by their peers. Stigmatisation is associated with a host
      of negative social and psychological effects, which impacts a young person's well
      being. As a result, the development of effective anti-stigma strategies is
      considered a major research priority. However, in order to design effective
      stigma reduction strategies, researchers must be informed by an understanding of
      the factors that influence the expression of stigma. Although evidence suggests
      that empathy and social norms have a considerable effect on adolescents' social
      attitudes and behaviours, research has yet to examine whether these factors
      significantly influence adolescents' responses toward their peers with mental
      health difficulties. Thus, this study aims to examine whether empathy (cognitive
      and affective) and peer norms (descriptive and injunctive) influence adolescents'
      implicit and explicit stigmatising responses toward peers with mental health
      problems. A total of 570 (221 male and 348 female; 1 non-specified) adolescents,
      aged between 13 and 18 years (M = 15.51, SD = 1.13), participated in this
      research. Adolescents read vignettes describing male/female depressed and
      'typically developing' peers. Adolescents answered questions assessing their
      stigmatising responses toward each target, as well as their empathic responding
      and normative perceptions. A sub-sample of participants (n=173) also completed an
      IAT assessing their implicit stigmatising responses. Results showed that
      descriptive norms exerted a substantial effect on adolescents' explicit
      responses. Cognitive empathy, affective empathy and injunctive norms exerted more
      limited effects on explicit responses. No significant effects were observed for
      implicit stigma. Overall, empathy was found to have limited effects on
      adolescents' explicit and implicit stigmatising responses, which may suggest that
      other contextual variables moderate the effects of dispositional empathy on
      responding. In conclusion, these findings suggest that tackling the perception of
      negative descriptive norms may be an effective strategy for reducing explicit
      stigmatising responses among adolescents.

PMID- 28753462
TI  - MicroRNAs and RNA binding protein regulators of microRNAs in the control of
      pluripotency and reprogramming.
AB  - Post-transcriptional and translational regulations play essential roles during
      cellular reprogramming and in the maintenance and differentiation of pluripotent
      stem cells (PSCs). MicroRNAs (miRNAs) control cell cycle, glycolysis, chromatin
      state, survival and pluripotency of ESCs. Likewise, many miRNAs assist or act as
      a barrier for the generation of induced pluripotent stem cells (iPSCs). Recent
      studies also reveal exciting new directions on miRNA functions in regulating the
      switch between naive and primed pluripotent states as well as the establishment
      of totipotent-like state. Furthermore, the biogenesis and function of
      pluripotency related miRNAs are regulated by various RNA binding proteins (RBPs)
      at different levels. Revealing the interplay between RBPs and miRNAs will advance
      our understanding of molecular mechanisms controlling pluripotency and provide
      better means to manipulate PSCs for clinical applications. In this review, we
      summarize recent findings on the function of miRNAs in ESCs and during
      reprogramming. In addition, we also discuss new directions on miRNA functions in
      regulating the switch between different pluripotent states and RBP-mediated
      regulation of miRNA biogenesis and function in pluripotency control.

PMID- 28753463
TI  - The impact of education on the probability of receiving periodontal treatment.
      Causal effects measured by using the introduction of a school reform in Norway.
AB  - The aim of the present study was to estimate the causal effect of education on
      the probability of receiving periodontal treatment in the adult Norwegian
      population. In Norway, a substantial part of the cost of periodontal treatment is
      subsidized by the National Insurance Scheme. In that case, one might expect that
      the influence of individual resources, such as education, on receiving treatment
      would be reduced or eliminated. Causal effects were estimated by using data on a
      school reform in Norway. During the period 1960-1972, all municipalities in
      Norway were required to increase the number of compulsory years of schooling from
      seven to nine years. The education reform was used to create exogenous variation
      in the education variable. The education data were combined with large sets of
      data from the Norwegian Health Economics Administration and Statistics Norway.
      Since municipalities implemented the reform at different times, we have both
      cross-sectional and time-series variation in the reform instrument. Thus we were
      able to estimate the effect of education on the probability of receiving
      periodontal treatment by controlling for municipality fixed effects and trend
      variables. The probability of receiving periodontal treatment increased by 1.4
      1.8 percentage points per additional year of schooling. This is a reasonably
      strong effect, which indicates that policies to increase the level of education
      in the population can be an effective tool to improve oral health, including
      periodontal health.

PMID- 28753464
TI  - Mortality and the relationship of somatic comorbidities to mortality in
      schizophrenia. A nationwide matched-cohort study.
AB  - AIM: We conducted a matched-cohort study to assess mortality in schizophrenia and
      the relationship of mortality with comorbid somatic conditions and suicide
      attempts. METHOD: A full-population register-based prospective matched-cohort
      study was performed including all eligible patients with schizophrenia in Hungary
      between 01/01/2005 and 31/12/2013. Control subjects were individually matched to
      patients with schizophrenia at a 5:1 ratio. The principal outcome measure was
      death due to any reason. A non-parametric approach was used for descriptive
      statistical purposes, the Kaplan-Meier model for survival analysis, and the Cox
      proportional-hazards regression model for inferential statistics. RESULTS:
      Patients with schizophrenia (n=65,169) had substantially higher risk of all-cause
      mortality than the control subjects (n=325,435) (RR=2.4; P<0.0001). Comorbidities
      and suicide attempts were associated with significantly increased mortality in
      both groups. As compared to the controls, 20-year old males with schizophrenia
      had a shorter life expectancy by 11.5years, and females by 13.7years; the
      analogous numbers for 45-year old schizophrenics were 8.1 and 9.6years,
      respectively. CONCLUSIONS: A significant mortality gap - mainly associated with
      somatic comorbidities - was detected between patients with schizophrenia and
      individually matched controls. Improved medical training to address the disparity
      in mortality, and many other factors including lack of resources, access to and
      model of medical care, lifestyle, medication side effects, smoking, stigma, need
      for early intervention and adequate health care organization could help to better
      address the physical health needs of patients with schizophrenia.

PMID- 28753465
TI  - Engineering an auto-activated R protein that is in vivo activated by a viral
      protease.
AB  - Autonomous hypersensitive responses (self-HRs) are caused by constitutively
      active R proteins. In this study, we identified an auto-activated form of the R
      gene Pvr9 (autoPvr9); the auto-activation results from an amino acid substitution
      between its NBS and LRR domains. Self-HR was strongly reduced or completely
      inhibited by fusion of an extra peptide to the autoPvr9 N-terminal or C-terminal,
      respectively. When an NIa recognition site was placed between autoPvr9 and the
      extra peptide, the fusion construct could trigger an NIa-dependent HR. Several C
      terminal fusions were tested, but only those that maintained detectable protein
      expression were capable of an NIa-dependent HR. Our results suggest the potential
      for transforming malfunctioning and auto-activated R proteins into a new
      construct targeting potyviral NIa proteases.

PMID- 28753466
TI  - Perceived barriers for cannabis cessation: Relations to cannabis use problems,
      withdrawal symptoms, and self-efficacy for quitting.
AB  - Cannabis is the most widely used illicit substance in the United States. Regular
      cannabis use appears to be a dynamic, chronic process consisting of multiple quit
      attempts, periods of reduction, periods of abstinence, and periods of continual
      use. Cannabis-related processes, including withdrawal, problematic consequences
      of use, and self-efficacy for quitting each contribute to the cycle of use and,
      in part, are maintained and reinforced by perceived barriers for cannabis
      cessation. Yet, no work has examined the association between perceived barriers
      for cannabis cessation and clinically-relevant processes related to cannabis use.
      To address this gap, the current study recruited a racially diverse sample
      (N=145, 63.4% Black or African American) of cannabis users from the community to
      test the hypothesis that greater perceived barriers for quitting cannabis was
      related to more cannabis use problems, more cannabis withdrawal symptoms, and
      lower self-efficacy for quitting cannabis. Structural equation modeling suggested
      that greater perceived barriers for quitting cannabis was uniquely associated
      with cannabis use problems (beta=0.50, 95%CI [0.39, 0.65], p<0.001), greater
      withdrawal symptoms (beta=0.39, 95%CI [0.30, 0.50], p<0.001), and lower self
      efficacy for quitting (beta=-0.17, 95%CI [-0.21, -0.02], p=0.028). The results of
      this study indicate perceived barriers for cannabis cessation may help in better
      understanding an array of clinically significant cannabis use processes. Indeed,
      the observed pattern of findings add to current theoretical models of substance
      use that aim to identify unique risk processes that may maintain substance use
      and provide valuable information that can be used to inform treatment for
      cannabis users.

PMID- 28753467
TI  - The association of SCN1A p.Thr1067Ala polymorphism with epilepsy risk and the
      response to antiepileptic drugs in Slovenian children and adolescents with
      epilepsy.
AB  - PURPOSE: The voltage-gated sodium channel SCN1A mutations are involved in
      epileptogenesis and may be associated with different epilepsy phenotypes. The
      SCN1A channel is also an important antiepileptic drug (AED) target. The aim of
      this study was to investigate if the SCN1A c.3184A>G/p.Thr1067Ala polymorphism
      modifies the epilepsy risk or is associated with the responsiveness to AEDs in
      Slovenian children and adolescents with epilepsy. METHODS: In total, 216
      paediatric patients with epilepsy were consecutively recruited during routine
      outpatient follow-up visits between January 2011 and December 2014. All patients
      and 95 healthy controls, all Central European Caucasians, were genotyped for the
      SCN1A c.3184A>G/p.Thr1067Ala polymorphism. Clinical data on all patients were
      collected retrospectively. The response to AEDs was classified as seizure
      remission (a minimum of one year of seizure freedom before inclusion) or no
      remission. Univariate and multivariate logistic regression was used to determine
      the association of genotypes with binary outcomes. RESULTS: 114 patients (52.8%)
      had achieved remission, while 102 (47.2%) had failed to do so. Carriers of at
      least one polymorphic SCN1A c.3184A>G/p.Thr1067Ala G allele tended to have a
      lower epilepsy risk (OR=0.38, 95% CI=0.18-0.79, P=0.010) and were significantly
      more likely to achieve remission (OR=2.00, 95% CI=1.16-3.46, P=0.013). Girls were
      less likely to achieve remission (P=0.055). Patients in remission tended to be
      older at first seizure in comparison to the group failing to achieve remission
      (OR=1.06, 95% CI=0.99-1.14, P=0.099), but this association did not reach
      statistical significance. CONCLUSION: The polymorphic SCN1A
      c.3184A>G/p.Thr1067Ala G allele was associated with a lower risk of epilepsy and
      a higher remission rate in Slovenian children and adolescents with epilepsy.

PMID- 28753468
TI  - Depression among Chinese older adults: A perspective from Hukou and health
      inequities.
AB  - BACKGROUND: Previous studies have suggested that socioeconomic status is linked
      to health status. However, most of these studies have been conducted in developed
      countries, whose social settings are different from those in China. Hukou
      (household registration) status, one of China's main socioeconomic indicators,
      has received limited attention in the literature. OBJECTIVES: The objective of
      this study was to examine the relationship between different Hukou statuses, and
      depression, among older adults in China. METHODS: The data were obtained from the
      China Health and Retirement Longitudinal Study (CHARLS). In total, 7409 Chinese
      older adults aged 60 and over were included in the survey. The Center for
      Epidemiologic Studies Depression Scale (CESD-10) was used to assess depressive
      symptoms. The various Hukou statuses were coded into four categories: villager,
      temporary rural-to-urban migrant, permanent rural-to-urban migrant and urban
      local citizen. RESULTS: The results indicated that the level of depressive
      symptoms was significantly higher among villagers (beta [beta] 1.40, 95%CI 0.83
      1.96), temporary migrants (beta [beta] 0.97 95%CI 0.38-1.56) and permanent
      migrants (beta [beta] 0.52 95%CI 0.04-1.00) than among urban local citizens. In
      addition, people who had experienced changes in their Hukou status before age 16
      were more likely to have depressive symptoms (beta [beta] 1.39, 95% CI 0.20
      2.58). LIMITATIONS: Being cross-sectional, this study is insufficient for
      determining causal relationships between Hukou status and depression.
      CONCLUSIONS: Our findings suggest that deeper reform of the Hukou system, and
      greater efforts to eliminate the health disparities associated with that system,
      are needed in China.

PMID- 28753469
TI  - NK1 receptor antagonists for depression: Why a validated concept was abandoned.
AB  - BACKGROUND: NK1 receptor antagonists were abandoned despite antidepressant
      efficacy in five randomized clinical trials. The loss of confidence may be
      attributed to the failure of a Phase III clinical program with the NK1 receptor
      antagonist aprepitant in Major Depression. This review examines how PET receptor
      occupancy was used to select doses for aprepitant and that these may not have
      achieved adequate exposure. METHODS: PubMed, Google Scholar, and FDA databases
      were searched for articles concerning NK1 receptor antagonists, human PET
      receptor occupancy and clinical trials in Major Depression. RESULTS:
      Antidepressant efficacy was initially demonstrated with three NK1 receptor
      antagonists, including aprepitant. A nanoparticle formulation of aprepitant was
      then developed to improve oral bioavailability. In PET studies, doses of 80 and
      160mg achieved a high level (~ 90%) of occupancy of NK1 receptors in the human
      brain and were selected for Phase III. The efficacy of these doses of the
      nanoparticle formulation may not have been established in depressed patients
      prior to Phase III, and previous formulations required a dose of 300mg of
      aprepitant for efficacy. No antidepressant effect of 80 or 160mg of aprepitant
      was found, and it was concluded that the NK1 antagonist concept was flawed.
      However, subsequent studies with other compounds showed that a higher level of
      NK1 receptor occupancy (100%) was required for antidepressant efficacy.
      LIMITATIONS: Key data concerning the bioequivalence of different formulations of
      aprepitant have not been published. The importance of NK1 antagonists for
      pharmacotherapy of depression and other psychiatric disorders has not been
      established in clinical practice. CONCLUSION: Aprepitant may have failed in Phase
      III because of an inadequate understanding of the relationship between brain NK1
      receptor occupancy and clinical response. A validated and novel mechanistic
      approach to treat depression has been misperceived as ineffective and abandoned.
      Caution should be exercised in the appropriate use of PET occupancy data to
      select doses for drug development programs in neuropsychiatry. The relationship
      between exposure, receptor occupancy and clinical response should be established.
      A crisis of confidence has followed the failure of this and other programs in
      neuropsychiatry, with a far reaching and detrimental impact on pharmaceutical
      research.

PMID- 28753470
TI  - Re-analysis of the association of temperature or sunshine with hyperthymic
      temperament using lithium levels of drinking water.
AB  - BACKGROUND: The Japanese archipelago stretches over 4000km from north to south
      and has four large islands: Hokkaido, Honshu, Shikoku, and Kyushu. Previously,
      using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto
      questionnaire version (TEMPS-A), we compared the hyperthymic scores of residents
      in Sapporo, Obihiro, Takaoka, Koshigaya, and Oita cities (which are located at
      latitudes of 43 degrees N, 42 degrees N, 36 degrees N, 36 degrees N and 33
      degrees N with various combinations of ambient temperament and sunshine in Japan,
      respectively). We found that latitude predicted significant variance in
      hyperthymic temperament, and that ambient temperature, but not sunshine,
      significantly affected hyperthymic temperament scores. However, the analysis
      failed to consider the effects of naturally occurring low-dose lithium on
      temperament. METHODS: In addition to the TEMPS-A data previously collected, we
      measured lithium levels of the five cities. The effect of temperature, sunshine,
      and lithium levels on hyperthymic temperament was analyzed for the five cities.
      RESULTS: A stepwise multiple regression analysis revealed that lithium levels as
      well as latitude, but not temperature or sunshine, predicted significant variance
      in hyperthymic temperament scores. Hyperthymic temperament scores were
      significantly and positively associated with lithium levels whereas they were
      significantly and negatively associated with latitude. LIMITATIONS: The light,
      temperature, lithium exposure that residents actually received was not measured.
      The number of regions studied was limited. The findings might not be generalized
      to residents across Japan or other countries. CONCLUSIONS: The present findings
      suggest that lithium in drinking water may positively maintain hyperthymic
      temperament, and that latitude may negatively maintain it.

PMID- 28753471
TI  - Neural differences underlying face processing in veterans with TBI and co
      occurring TBI and PTSD.
AB  - BACKGROUND: Traumatic brain injury (TBI) is common in military personnel and
      associated with high rates of posttraumatic stress disorder (PTSD). TBI impacts
      widely-distributed neural patterns, some of which influence affective processing.
      Better understanding how TBI and PTSD/TBI alters affective neural activity may
      improve our understanding of comorbidity mechanisms, but to date the neural
      correlates of emotional processing in these groups has been relatively
      understudied. METHODS: Military controls, military personnel with a history of
      TBI, and military personnel with both TBI and PTSD (N = 53) completed an
      emotional face processing task during fMRI. Whole-brain activation and functional
      connectivity during task conditions were compared between groups. RESULTS: Few
      whole-brain group differences emerged in planned pairwise contrasts, though the
      TBI group showed some areas of hypoactivation relative to other groups during
      processing of faces versus shapes. The PTSD/TBI group compared to the control and
      TBI groups demonstrated greater connectivity between the amygdala and insula seed
      regions and a number of prefrontal and posterior cingulate regions. LIMITATIONS:
      Generalizability to other patient groups, including those with only PTSD, has not
      yet been established. CONCLUSION: TBI alone was associated with hypoactivation
      during a condition processing faces versus shapes, but PTSD with TBI was
      associated altered functional connectivity between amygdala and insula regions
      and cingulate and prefrontal areas. Altered connectivity patterns across groups
      suggests that individuals with PTSD/TBI may need to increase frontal connectivity
      with the insulae in order to achieve similar task-based activity.

PMID- 28753472
TI  - Longitudinal mood monitoring in bipolar disorder: Course of illness as revealed
      through a short messaging service.
AB  - BACKGROUND: Online self-monitoring of mood can be used to investigate differences
      in course patterns across patient groups. This study explored the feasibility of
      remote symptom capture with True Colours, a self-rated online mood monitoring
      tool completed on a weekly basis. METHODS: Participants with bipolar disorder (N
      = 297) completed weekly depression and mania questionnaires over an average of
      27.5 months (range 1 -81 months). Subgroups defined by sex, age, and bipolar I
      vs. II status were compared on time in various mood states, number of episodes,
      and week-to-week mood variability. RESULTS: Compliance with weekly questionnaires
      was generally high (median, 92% of weeks). Mood symptoms occurred for an average
      of 55.4% of weeks across the follow-up period. Females spent more time with
      hypomanic/manic and depressive symptoms and had more depressive episodes compared
      to males. Younger participants were found to experience more hypomanic/manic
      episodes and showed greater variability in mood symptoms than older participants.
      No significant differences in mood symptoms or variability were observed between
      bipolar I and II patients. LIMITATIONS: This was a naturalistic study with a
      heterogeneous cohort, and did not include a control group. True Colours does not
      identify mood fluctuations that may occur in the days between weekly assessments.
      CONCLUSIONS: Monitoring moods through an online tool is both feasible and
      informative regarding course of illness in patients with bipolar disorder.
      Interventions aiming to reduce mood variability and manic/hypomanic episodes in
      the early phases of bipolar disorder may enhance the long-term symptomatic course
      of the illness.

PMID- 28753473
TI  - Reduction mammaplasty in patients with history of breast cancer: The incidence of
      occult cancer and high-risk lesions.
AB  - INTRODUCTION: Contralateral reduction mammaplasty is regularly included in the
      treatment of breast cancer patients. We analyzed the incidence of occult breast
      cancer and high-risk lesions in reduction mammaplasty specimens of women with
      previous breast cancer. We also analyzed if timing of reduction mammaplasty in
      relation to oncological treatment influenced the incidence of abnormal findings,
      and compared if patients with abnormal contralateral histopathology differed from
      the study population in terms of demographics. MATERIALS AND METHODS: The study
      consisted of 329 breast cancer patients, who underwent symmetrizing reduction
      mammaplasty between 1/2007 and 12/2011. The data was retrospectively analyzed for
      demographics, operative and histopathology reports, oncological treatment, and
      postoperative follow-up. RESULTS: Reduction mammaplasty specimens revealed
      abnormal findings in 68 (21.5%) patients. High-risk lesions (ADH, ALH, and LCIS)
      were revealed in 37 (11.7%), and cancer in six (1.9%) patients. Abnormal
      histopathology correlated with higher age (p = 0.0053), heavier specimen (p =
      0.0491), and with no previous breast surgery (p < 0.001). Abnormal
      histopathological findings were more frequent in patients with reduction
      mammaplasty performed prior to oncological treatment (p < 0.001), and in patients
      with immediate reconstruction (p = 0.0064). CONCLUSION: The incidences of
      malignant and high-risk lesions are doubled compared to patients without prior
      breast cancer. Patients with abnormal histopathology cannot be preoperatively
      identified based on demographics. If reduction mammaplasty is performed before
      oncological treatment, the incidence of abnormal findings is higher. In the light
      of our results, contralateral reduction mammaplasty with histopathological
      evaluation in breast cancer patients offers a sophisticated tool to catch those
      patients whose contralateral breast needs increased attention.

PMID- 28753474
TI  - Age-related changes in envelope-following responses at equalized peripheral or
      central activation.
AB  - Previous work has debated about the comparisons of hearing abilities faced with
      alterations in hearing thresholds and evoked potentials between groups following
      acoustic trauma- or age-related changes. This study compares envelope-following
      responses (EFRs) of young and aged rats when sound levels were matched according
      to (1) wave I amplitudes of auditory brainstem responses (ABRs) elicited by 8-kHz
      tones or (2) EFR amplitudes evoked by sinusoidally amplitude-modulated (SAM)
      tones at 100% depth. Matched wave I amplitudes across age corresponded to
      approximately 20-dB sound level differences. For matched wave I, no age-related
      differences were observed in wave V amplitudes. However, EFRs recorded in silence
      were enhanced with aging at 100% but not at 25% depth, consistent with enhanced
      central gain in aging. For matched EFRs, there were no age-related differences in
      EFRs of amplitude modulation (AM) depth and AM frequency processing. These
      results suggest novel, objective measures beyond threshold to compensate for
      differences in auditory nerve activation and to differentiate peripheral and
      central contributions of EFRs.

PMID- 28753475
TI  - Presenilin 1 mutation decreases both calcium and contractile responses in
      cerebral arteries.
AB  - Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early
      onset Alzheimer's disease or sporadic late-onset Alzheimer's disease,
      respectively. PS1 has been essentially studied in neurons and its mutation was
      shown to alter intracellular calcium (Ca2+) signals. Here, we showed that PS1 is
      expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we
      assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca2+ signals
      and contractile responses of vascular SMC. Agonist-induced contraction of
      cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo.
      Spontaneous activity of Ca2+ sparks through ryanodine-sensitive channels (RyR)
      was unchanged, whereas the RyR-mediated Ca2+-release activated by caffeine was
      shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation
      decreased the caffeine-activated capacitive Ca2+ entry, and inhibitors of SERCA
      pumps reversed the effects of PS1dE9 on Ca2+ signals. PS1dE9 mutation also leads
      to the increased expression of SERCA3, phospholamban, and RyR3. These results
      show that PS1 plays a crucial role in the cerebrovascular system and the vascular
      reactivity is decreased through altered Ca2+ signals in PS1dE9 mutant mice.

PMID- 28753476
TI  - Stroke diagnosis associated with thrombophilia testing overutilization.

PMID- 28753477
TI  - The role of von Willebrand factor in primary haemostasis under conditions of
      haemodilution.
AB  - INTRODUCTION: Severe blood loss and related haemodilution during cardiac surgery
      result in a reduced platelet count which may lead to impaired primary
      haemostasis. Additionally, the reduced haematocrit lowers rheological forces in
      circulation and may account for lowered platelet adhesiveness and potentially
      reduced von Willebrand factor (VWF) activity. These mechanisms may lead to
      postoperative bleeding. Aim of this study was the examination of VWF activity and
      VWF-mediated platelet adhesion to collagen under conditions of haemodilution.
      MATERIALS AND METHODS: An in vitro flow chamber was utilized to examine the
      primary haemostasis under a high arterial shear rate of 1500s-1 at variable VWF
      concentrations, platelet counts and haematocrit levels. RESULTS: Under a high
      arterial shear rate, VWF activity is highly dependent on blood viscosity. Both
      VWF-collagen binding and VWF-mediated platelet adhesion to collagen were
      significantly increased with increasing haematocrit. Interestingly, we found
      slight differences in the VWF multimer sizes able to bind collagen under
      different shear stress conditions. Under conditions of haemodilution, platelet
      adhesion was strongly dependent on VWF concentration. Increasing VWF
      concentration improved platelet adhesiveness under low haematocrit conditions
      (30%) and variable platelet counts (80, 150 and 250*109/L). This effect was
      nearly abolished at very low platelet count levels of 50*109/L. CONCLUSIONS: VWF
      improves platelet function under conditions of haemodilution. Therefore,
      increasing VWF concentration may represent a complementary strategy to
      administration of platelet concentrates for the management of bleeding in
      thrombocytopenia.

PMID- 28753478
TI  - Extensive screening for occult malignancy in unprovoked venous thromboembolism: A
      meta-analysis.
AB  - BACKGROUND: The present meta-analysis aimed to evaluate the efficacy and
      sensitivity of an extensive screening strategy for occult malignant diseases in
      patients with unprovoked venous thromboembolism (VTE). METHODS: We conducted a
      systematic search of PubMed, Cochrane, EMBASE, and relevant article references.
      Meta-analysis was used to pool weighted relative risks (RR) for the rate of
      missed diagnosis, all-cause mortality, and cancer-related mortality.
      Heterogeneity test was performed using the inconsistency index. Furthermore,
      pooled analysis of the sensitivity and the proportion of false-positive findings
      of PET/CT were conducted. RESULTS: A total of 5 controlled studies were included
      with 1,115 and 1,159 unprovoked VTE patients receiving limited or extensive
      screening strategy, respectively. The risk of missed diagnosis (RR, 0.51; 95% CI,
      0.20-1.28; P=0.15) was not significantly different between the limited and
      extensive screening group. Moreover, there was no statistically significant
      difference in all-cause mortality (RR, 0.86; 95% CI, 0.58-1.27; P=0.44) and
      cancer-related mortality (RR, 0.86; 95% CI, 0.46-1.62; P=0.65) between the two
      groups. The pooled sensitivity and proportion of false-positive findings of
      PET/CT as a screening tool for occult malignancy in patients with unprovoked VTE
      was 95% (95% CI, 38%-100%) and 33% (95% CI, 20%-47%), respectively. CONCLUSIONS:
      Extensive screening strategy did not show a clinically significant benefit over
      limited screening strategy. Considering the high cost and the additional physical
      and emotional harm, current evidence did not support extensive screening for each
      patient in the setting.

PMID- 28753479
TI  - Advanced CerMet ceramic composites for medical applications.
AB  - Implantable active devices such as pacemakers are facing rigorous requirements.
      Because they reside within the body for years, materials applied in this
      surrounding must exhibit biocompatibility and extraordinary reliability. They
      also have to provide a number of functional properties. In this work we present a
      method that enables the realization of a highly complex profile of properties by
      means of a dual composite approach. Using multilayer technology, an electrical
      conductor is embedded into a ceramic matrix, thus, creating conductive paths that
      are insulated from each other. In addition to this macroscopically hybrid
      architecture, this approach features a second composite aspect: the conductor is
      not composed of a single metallic phase, but is a ceramic-metal mixture. Owing to
      its interpenetrating microstructure, this CerMet allows for a strong and hermetic
      integration of the conductor into the ceramic matrix otherwise impossible due to
      mismatch in thermal expansion. In fact, the CerMet ceramic composite exhibits a
      higher strength than the pure ceramic as revealed by a three-point bending test
      study. At the same time, the CerMet offers high and virtually metal-like
      conductor properties, enabling a down-scaling of the conductive paths to 150um
      diameter and smaller. Furthermore, the described composite is biocompatible, non
      magnetic, and chemically inert, which is vital for the application in active,
      implantable, medical devices. Beside the general fabrication route, we present
      the microstructural, functional, and mechanical properties of this newly
      developed class of dual composites.

PMID- 28753480
TI  - DSM-5 substance use disorders among adult primary care patients: Results from a
      multisite study.
AB  - BACKGROUND: There are limited data about the extent of DSM-5 substance use
      disorders (SUDs) among primary care patients. METHODS: This study analyzed data
      from a multisite validation study of a substance use screening instrument
      conducted in a diverse sample of 2000 adults aged >=18 years recruited from five
      primary care practices in four states. Prevalence and correlates of 12-month DSM
      5 SUDs were examined. RESULTS: Overall, 75.5% of the sample used any substance,
      including alcohol (62.0%), tobacco (44.1%), or illicit drugs/nonmedical
      medications (27.9%) in the past 12 months (marijuana 20.8%, cocaine 7.3%, opioids
      4.8%, sedatives 4.1%, heroin 3.9%). The prevalence of any 12-month SUD was 36.0%
      (mild disorder 14.2%, moderate/severe disorder 21.8%): tobacco 25.3% (mild 11.5%,
      moderate/severe 13.8%); alcohol 13.9% (mild 6.9%, moderate/severe 7.0%); and any
      illicit/nonmedical drug 14.0% (mild 4.0%, moderate/severe 10.0%). Among past 12
      month users, a high proportion of tobacco or drug users met criteria for a
      disorder: tobacco use disorder 57.4% (26.1% mild, 31.3% moderate/severe) and any
      drug use disorder 50.2% (14.3% mild, 35.8% moderate/severe); a lower proportion
      of alcohol users (22.4%) met criteria for alcohol use disorder (11.1% mild, 11.3%
      moderate/severe). Over 80% of adults with opioid/heroin use disorder met criteria
      for a moderate/severe disorder. Younger ages, male sex, and low education were
      associated with increased odds of having SUD. CONCLUSION: These findings reveal
      the high prevalence of SUDs in primary care and underscore the need to identify
      and address them.

PMID- 28753481
TI  - Baclofen and naltrexone effects on alcohol self-administration: Comparison of
      treatment initiated during abstinence or ongoing alcohol access in baboons.
AB  - BACKGROUND: Baclofen, a GABAB receptor agonist, is under investigation as a
      pharmacotherapy for alcohol use disorder. Treatment with a pharmacotherapeutic
      can be initiated during alcohol abstinence or active drinking, which may
      influence treatment outcomes. This study examined whether baclofen treatment
      initiated and maintained during alcohol abstinence would reduce alcohol seeking
      and self-administration upon return to alcohol access, and whether effects
      differed from treatment initiated and maintained during ongoing alcohol access.
      Naltrexone was tested under similar conditions for comparison. METHODS: Five
      baboons self-administered alcohol under a three-component chained schedule of
      reinforcement that modeled periods of anticipation (Component 1), seeking
      (Component 2), and consumption (Component 3). Alcohol was only available in
      Component 3. In Experiment 1, baclofen (0.1-1.8mg/kg) or naltrexone (1.0
      5.6mg/kg) was administered daily beginning on the first day of a 5-day abstinence
      period and treatment was continued for 5days of alcohol access. In Experiment 2,
      selected doses of both drugs were administered during ongoing alcohol access.
      RESULTS: When treatment was initiated during alcohol abstinence, baclofen and
      naltrexone did not significantly reduce total alcohol intake (g/kg) or alcohol
      seeking. In comparison, when treatment was initiated during ongoing alcohol
      access, both baclofen (1.8mg/kg) and naltrexone (3.2 and 5.6mg/kg) significantly
      reduced total alcohol intake (g/kg). Naltrexone (5.6mg/kg), but not baclofen,
      significantly reduced alcohol seeking. CONCLUSIONS: Initiation of baclofen
      treatment (or other alcohol use disorder treatments) during abstinence or active
      drinking may be an important factor in influencing efficacy and appropriate dose
      selection.

PMID- 28753482
TI  - Gestational diabetes and offspring birth size at elevated environmental pollutant
      exposures.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased
      availability of glucose and macronutrients in fetal circulation and macrosomia.
      Therefore, the role of GDM in the association between metabolism-disrupting
      chemicals and birth size deserves attention. OBJECTIVE: We examined whether GDM
      may mediate or modify the associations between maternal environmental pollutant
      exposures and offspring birth size measures. METHODS: We analyzed 604 Faroese
      pregnant women and their offsprings born in 1997-2000. Maternal pregnancy serum
      concentrations of organochlorine compounds (OCs: polychlorinated biphenyl (PCB)
      congeners and dichlorodiphenyldichloroethylene (DDE)), and five perfluoroalkyl
      substances (PFASs), and hair and cord blood mercury concentrations were measured.
      We used regression (single-pollutants) and structural equation models (SEMs)
      (multiple-pollutant analyses using latent constructs of OCs, PFASs and mercury)
      to estimate the associations with GDM and birth size measures, accounting for
      mediation and/or effect modification by GDM. RESULTS: Serum-DDE and hair-mercury
      concentrations were associated with GDM (adjusted OR per concentration doubling:
      1.29; 95% CI: 0.94, 1.77 for DDE, and 0.79; 95% CI: 0.62, 0.99 for mercury), but
      in multiple pollutant-adjusted SEMs only a positive association between OC
      exposure and GDM remained significant (change in GDM odds per OC doubling: 0.45;
      95% CI: 0.05, 0.86). PCB and overall OC exposure were positively associated with
      head circumference (SEM; mean change per OC doubling: 0.13cm; 95% CI, 0.01.
      0.25). Overall PFAS exposure was inversely associated with birth weight (SEM;
      mean change per PFAS doubling: -169g; 95% CI: -359, 21), and for many single
      PFASs we found a pattern of inverse associations with birth weight and head
      circumference in boys, and positive or null associations in girls. None of the
      environmental pollutants was associated with offspring length. GDM neither
      modified nor mediated the associations with birth size measures. CONCLUSIONS: We
      found associations with GDM and offspring birth size to be specific to the
      environmental pollutant or pollutant group. Associations with birth size measures
      appear to be independent of GDM occurrence.

PMID- 28753483
TI  - Maternal exposure to ambient air pollution and fetal growth in North-East
      Scotland: A population-based study using routine ultrasound scans.
AB  - BACKGROUND: Maternal ambient air pollution exposure is associated with reduced
      birthweight. Few studies have examined the effect on growth in utero and none
      have examined the effect of exposure to particulates less than 2.5um (PM2.5) and
      possible effect modification by smoking status. OBJECTIVES: Examine the effect of
      maternal exposure to ambient concentrations of PM10, PM2.5 and nitrogen dioxide
      (NO2) for in utero fetal growth, size at birth and effect modification by smoking
      status. METHODS: Administratively acquired second and third trimester fetal
      measurements (bi-parietal diameter, femur length and abdominal circumference),
      birth outcomes (weight, crown heel length and occipito-frontal circumference) and
      maternal details were obtained from routine fetal ultrasound scans and maternity
      records (period 1994-2009). These were modelled against residential annual
      pollution concentrations (calendar year mean) adjusting for covariates and
      stratifying by smoking status. RESULTS: In the whole sample (n=13,775
      pregnancies), exposure to PM10, PM2.5 and NO2 was associated with reductions in
      measurements at birth and biparietal diameter from late second trimester onwards.
      Among mothers who did not smoke at all during pregnancy (n=11,075), associations
      between biparietal diameter and pollution exposure remained significant but were
      insignificant among those who did smoke (n=2700). Femur length and abdominal
      circumference were not significantly associated with pollution exposure.
      CONCLUSIONS: Fetal growth is strongly associated with particulates exposure from
      later in second trimester onwards but the effect appears to be subsumed by
      smoking. Typical ambient exposures in this study were relatively low compared to
      other studies and given these results, it may be necessary to consider reducing
      recommended "safe" ambient air exposures.

PMID- 28753484
TI  - Directional effect in double conditionals with a construction task: The semantic
      hypothesis.
AB  - The goal of this paper is to test the main predictions of the semantic hypothesis
      about the directional effect in double conditionals (such as, 'A only if B/only
      if C, B') with a construction task. The semantic hypothesis claims that
      directional effect can be explained by the inherent directionality of the
      relation between the relatum and the target object of the premises. According to
      this hypothesis, a directional effect should occur if only one of the end-terms
      of the premises takes the role of relatum: a) if the end-term that plays the role
      of relatum is in the first premise, a forward directional effect is predicted
      (from A to C); and b) if the end-term that plays the role of relatum is in the
      second premise, a backward directional effect is predicted (from C to A). On the
      other hand, it claims that there should be no directional effect when both end
      terms take the role of relatum or when neither of the end-terms plays the role of
      relatum. Three experiments confirmed the main predictions of the semantic
      hypothesis in a construction task.

PMID- 28753485
TI  - Age-related differences in social influence on risk perception depend on the
      direction of influence.
AB  - Adolescents are particularly susceptible to social influence. Here, we
      investigated the effect of social influence on risk perception in 590
      participants aged eight to fifty-nine-years tested in the United Kingdom.
      Participants rated the riskiness of everyday situations, were then informed about
      the rating of these situations from a (fictitious) social-influence group
      consisting of teenagers or adults, and then re-evaluated the situation. Our first
      aim was to attempt to replicate our previous finding that young adolescents are
      influenced more by teenagers than by adults. Second, we investigated the social
      influence effect when the social-influence group's rating was more, or less,
      risky than the participants' own risk rating. Younger participants were more
      strongly influenced by teenagers than by adults, but only when teenagers rated a
      situation as more risky than did participants. This suggests that stereotypical
      characteristics of the social-influence group - risk-prone teenagers - interact
      with social influence on risk perception.

PMID- 28753486
TI  - Efficacy and safety of empagliflozin in Japanese patients with type 2 diabetes
      mellitus: A sub-analysis by body mass index and age of pooled data from three
      clinical trials.
AB  - AIMS: To investigate the efficacy and safety of empagliflozin in subgroups based
      on body mass index (BMI) and age, using a pooled data set from Japanese patients
      with type 2 diabetes mellitus (T2DM). METHODS: Pooled data from 1403 patients
      treated with empagliflozin at 10mg/day or 25mg/day in three clinical studies
      (>=52week treatment) were stratified by baseline BMI (<22, 22 to <25 and
      >=25kg/m2) and baseline age (<50, 50 to <65 and >=65years). RESULTS:
      Empagliflozin at 10mg/day and 25mg/day reduced mean glycated hemoglobin (HbA1c) (
      0.77 to -0.87% and -0.76 to -0.97%, respectively), mean fasting plasma glucose
      (FPG) (-20.79 to -27.06mg/dL and -26.08 to -29.60mg/dL) and mean body weight (
      3.4 to -4.7% and -3.7 to -4.7%) in all subgroups of baseline BMI and age,
      regardless of age and degree of obesity. Adverse events were observed in
      approximately 70-80% patients in BMI and age subgroups of both empagliflozin
      groups. No hypoglycemia requiring assistance was observed. Neither UTI nor
      genital infection rates differed markedly among the BMI and age subgroups. Volume
      depletion was increased in patients >=65years of age as compared to younger
      patients. CONCLUSIONS: Empagliflozin was well tolerated and improved HbA1c, FPG
      and body weight in all BMI and age subgroups of Japanese patients with T2DM,
      regardless of age and degree of obesity. Empagliflozin is considered to be
      effective and well tolerated for treating a wide range of Japanese patients with
      T2DM. TRIAL REGISTRATION: Study 1 (NCT01193218), Study 2 (NCT01289990) and Study
      3 (NCT01368081).

PMID- 28753487
TI  - Comparative study on tribological mechanisms of polyimide composites when sliding
      against medium carbon steel and NiCrBSi.
AB  - Tribological behaviors of various polyimide (PI) composites when rubbing with
      medium carbon steel (MCS35) and NiCrBSi, were comprehensively investigated. When
      the conventional PI composite filled with carbon fibers and graphite was
      concerned, the carbon-based tribofilm formed on NiCrBSi surface resulted in
      obvious friction- and wear-reduction. However, no lubricating tribofilm was
      formed on MCS35 surface. Chelation of polymeric molecular radicals with the
      metallic counterparts was identified on the worn surfaces. Theoretical
      calculations corroborated that the Ni-based metal-organic compound showed a
      higher stability than the Fe-based one. With respect to the sliding of the hybrid
      nanocomposites containing silica or h-BN nanoparticles, the nanoparticles
      released onto the interface significantly mitigated tribo-oxidation of metallic
      counterparts, and were finally tribo-sintered into a compact layer after being
      mixed with remnant polymer and tribo-oxidation products. The effect of
      counterpart material was less pronounced for the tribological mechanisms of the
      nanocomposites than for the conventional composite.

PMID- 28753488
TI  - Extensive and selective adsorption of ZIF-67 towards organic dyes: Performance
      and mechanism.
AB  - Zeolitic imidazolate frameworks-67 (ZIF-67) was prepared via electrochemical
      deposition, which was used to conduct adsorptive removal of various organic dyes.
      The results revealed that ZIF-67 displayed good adsorption performance towards
      some dyes due to its positive Zeta potential at wide pH range or some special
      functional groups like SO3 of dyes. Also, ZIF-67 could separate some dyes from
      the matrix subjected to its preferential uptake towards certain dyes. The
      possible adsorption mechanism including electrostatic interactions, coordination
      interactions and hydrogen bonding interactions was proposed and tested.

PMID- 28753489
TI  - A versatile method for fabricating ion-exchange hydrogel nanofibrous membranes
      with superb biomolecule adsorption and separation properties.
AB  - Construction ion-exchange membranes with superb biomolecules adsorption and
      purification performance plays a greatly important role in the fields of
      biotechnological and biopharmaceutical industry, yet still remains an extremely
      challenging. Herein, we in situ synthesized the cis-butenedioic anhydride grafted
      poly(vinyl alcohol) hydrogel nanofibrous membranes (CBA-g-PVA HNFM) by combining
      electrospinning technique with the grafting-copolymerization crosslinking. Taking
      advantages of the large specific surface area which could provide numerous sites
      available for functional groups and biomolecules binding, highly tortuous and
      interconnected porous channel for biomolecules transfer, and enhanced mechanical
      strength, the resultant CBA-g-PVA HNFM exhibited relatively high binding amount
      of 170mgg-1, rapid equilibrium time of 8h towards the biomolecule template of
      lysozyme, and the performance could be tailored by regulating the buffer
      properties and protein concentrations. Additionally, the resultant functional
      HNFM also possessed superior acid resistance property, excellent reversibility
      and regeneration performance. More importantly, the obtained CBA-g-PVA HNFM could
      directly extract lysozyme from fresh chicken eggs with capacity of 125mgg-1,
      exhibiting excellent practical application properties. The fabrication of
      proposed CBA-g-PVA HNFM offers a feasible alternative for construction of ion
      exchange chromatograph column for bio-separation and purification engineering.

PMID- 28753490
TI  - Effect of tunable redox behavior of bis chelate substituted 1,10-phenantroline
      Cu(II) complexes on its reaction with superoxide anion in DMSO. Toward a simple
      criterion to identify a SOD-like mechanism.
AB  - In this work we report a series of Cu(II) complexes [Cu(N-N)2(X)]+, (N
      N=substituted 1,10-phenanthroline derivatives and X=Cl- or NO3-), with tunable
      E1/2 for electrochemical reduction [CuII(N-N)2(X)]++1e-?[CuI(N-N)2]+X-. The
      disproportion of O2*- was explored in presence of the electro-generated species
      [CuI(N-N)2]+ using cyclic voltammetry in a non-aqueous media, arising a new
      simple method to propose a SOD-like mechanism, which can be used as a quick guide
      test for a compound, before being proven in biological assays. It was found that
      complexes with high negative half wave potential values (E1/2) for Cu(II)/Cu(I)
      couple shown a current increment for oxygen reduction, related to the capability
      of the disproportion of this reactive oxygen species.

PMID- 28753491
TI  - Aryl-1H-imidazole[4,5f][1,10]phenanthroline Cu(II) complexes: Electrochemical and
      DNA interaction studies.
AB  - The reaction of aryl imidazo[4,5f] [1,10]phenanthrolines with Cu(NO3)2 lead to
      the formation of Cu(II) complexes of the type [Cu(L)(NO3)2] where L=PIP, 2
      (phenyl) [4,5f] imidazo phenanthroline; HPIP=2-(2-hydroxyphenyl)imidazo [4,5f]
      phenanthroline and NIP=2-(naphthyl) [4,5f] imidazo phenanthroline. The
      interaction of these complexes with calf thymus DNA has been studied using
      viscosity measurements, UV-visible and fluorescence spectroscopy. Chemical
      nuclease activity of these complexes has also been investigated. All complexes
      cleave DNA via oxidative pathway involving singlet oxygen. Molecular docking
      studies revealed that these complexes bind to DNA through minor groove.

PMID- 28753492
TI  - The influence of functional groups on the permeation and distribution of
      antimycobacterial rhodamine chelators.
AB  - We formerly hypothesized a mechanism whereby the antimycobacterial efficiency of
      a set of rhodamine labelled iron chelators is improved via the rhodamine
      fluorophore which enhances the chelators' permeation properties through
      membranes. To validate our hypothesis in a cellular context and to understand the
      influence of the structure of the fluorophore on the chelator's uptake and
      distribution within macrophages we now report comparative confocal microscopy
      studies performed with a set of rhodamine labelled chelators. We identify the
      functional groups of the chelator's framework that favor uptake by macrophages
      and conclude that the antimycobacterial effect is strongly related with the
      capacity of the chelator to distribute within the host cell and its compartments,
      a property that is closely related with the chelators' ability to interact with
      membranes. The quantification of the chelators' interaction with membranes was
      assessed through measurement of the corresponding partition constants in
      liposomes. The overall results support that the compounds which are
      preferentially taken up are the most efficient antimycobacterial chelators and
      for that reason we infer that the biological activity is modulated by the
      structural features of the fluorophore.

PMID- 28753493
TI  - Charge-transfer interactions of Cr species with DNA.
AB  - Interactions of Cr species with nucleic acids in living organisms depend strongly
      on Cr oxidation state and the environmental conditions. As the effects of these
      interactions range from benign to pre-mutagenic to carcinogenic, careful
      assessment of the hazard they pose to human health is necessary. We have
      investigated methods that would enable quantifying the DNA damage caused by Cr
      species under varying environmental conditions, including UV, O2, and redox
      potential, using simple instrumental techniques which could be in future combined
      into a field-deployable instrumentation. We have employed electrochemical quartz
      crystal nanogravimetry (EQCN), cyclic voltammetry (CV), and electrochemical
      impedance spectroscopy (EIS) to evaluate the extent of DNA damage expressed in
      terms of guanine oxidation yield (eta) and changes in specific characteristics
      provided by these techniques. The effects of the interactions of Cr species with
      DNA were analyzed using a model calf thymus DNA (ctDNA) film on a gold electrode
      (Au@ctDNA) in different media, including: (i) Cr(VI), (ii) Cr(VI) reduced at 
      0.2V, (iii) Cr(III)+UV radiation+O2, and Cr(III), obtaining the eta values: 7.4+/
      1.4, 1.5+/-0.4, 1.1+/-0.31%, and 0%, respectively, thus quantifying the hazard
      posed. The EIS measurements have enabled utilizing the decrease in charge
      transfer resistance (Rct) for ferri/ferrocyanide redox probe at an Au@ctDNA
      electrode to assess the oxidative ctDNA damage by Cr(VI) species. In this case,
      circular dichroism indicates an extensive damage to the ctDNA hydrogen bonding.
      On the other hand, Cr(III) species have not induced any damage to ctDNA, although
      the EQCN measurements show an electrostatic binding to DNA.

PMID- 28753494
TI  - Ovarian steroids, oxytocin, and tumor necrosis factor modulate equine oviduct
      function.
AB  - The oviduct plays important roles in the early reproductive process. The aim of
      this study was to evaluate gene transcription and protein expression of
      progesterone receptor (PGR), estrogen receptors 1 (ESR1) and 2 (ESR2); oxytocin
      receptor (OXTR); prostaglandin F2alpha synthase (AKR1C3), and prostaglandin E2
      synthase (Ptges) in mare oviduct in different estrous cycle stages. Estradiol
      (E2), progesterone (P4), oxytocin (OXT), and tumor necrosis factor alpha (TNF)
      effect on in vitro PGE2 and prostaglandin F2alpha (PGF2alpha) secretion by equine
      oviduct explants or by oviductal epithelial cells (OECs) were also assessed.
      During the breeding season, oviduct tissue was obtained post mortem from cyclic
      mares. Protein of ESR1, ESR2, PGR, AKR1C3, and Ptges was present in OECs, whereas
      OXTR was shown in oviduct stroma. In follicular phase, protein expression of
      ESR1, ESR2, PGR, and OXTR increased in oviduct explants (P < 0.05), whereas no
      estrous cycle effect was noted for AKR1C3 or Ptges. In follicular phase, mRNA
      transcription was upregulated for Pgr but downregulated for Oxtr, Ptges, and
      Akr1c3 (P < 0.05). Nevertheless, Esr1 and Esr2 mRNA levels did not change with
      the estrous cycle. In the ampulla, Esr1, Esr2, and Oxtr mRNA transcription
      increased, but not for Pgr or Ptges. In contrast, Akr1c3 mRNA level was
      upregulated in the infundibulum (P < 0.05). In follicular phase, E2, P4, and OXT
      downregulated PGE2 production by OEC (P < 0.05), but no difference was observed
      in mid-luteal phase. Explants production of PGE2 rose when treated with OXT in
      follicular phase; with TNF or OXT in early luteal phase; or with TNF, OXT, or P4
      in mid-luteal phase. PGF2alpha production by OEC was downregulated by all
      treatments in follicular phase but upregulated in mid-luteal phase (P < 0.05).
      Oviduct explants PGF2alpha production was stimulated by TNF or OXT in all estrous
      cycle phases. In conclusion, this work has shown that ESR1, ESR2, OXTR, Ptges,
      and AKRLC3 gene transcription and/or translation is estrous cycle dependent and
      varies with oviduct portion (infundibulum vs ampulla) and cell type. Ovarian
      steroid hormones, OXT and TNF stimulation of PGF2alpha and/or PGE2 production is
      also estrous cycle dependent and varies in the different portions of mare
      oviduct. Differential transcription level and protein localization in various
      portions of the oviduct throughout the estrous cycle, as well as PG production,
      suggest coordinated physiologic actions and mechanisms of steroid hormones, OXT,
      and TNF in the equine oviduct.

PMID- 28753495
TI  - Differential impact of lytic viruses on the taxonomical resolution of freshwater
      bacterioplankton community structure.
AB  - The significance of lytic viral lysis in shaping bacterial communities in
      temperate freshwater systems is less documented. Here we used Illumina sequencing
      of 16S rRNA genes to examine bacterial community structure and diversity in
      relation to variable viral lysis in the euphotic zone of 25 temperate freshwater
      lakes (French Massif Central). We captured a rich bacterial community that was
      dominated by a few bacterial classes and operational taxonomic units (OTUs)
      frequently detected in other freshwater ecosystems. In the investigated lakes
      with contrasting physico-chemical characteristics, the dominant bacterioplankton
      community was represented by major taxonomical orders, namely Actinomycetales,
      Burkholderiales, Sphingobacteriales, Acidimicrobiales, Flavobacteriales and
      Cytophagales covering about 70% of all sequences. Viral lysis was significantly
      correlated with the bacterial diversity indices (Chao, Shannon, OTUs) which
      explained about 33% and 45% of the variation in species diversity and observed
      richness respectively. Anosim and UniFrac analyses indicated a clear distinction
      of bacterial community structure among the lakes that exhibited high and low
      lytic viral infection (FIC) rates. Based on our findings, high FIC (>10%)
      supported higher species richness, whereas low FIC (<10%) resulted in less
      diverse community. Our study strongly suggests that lytic activity prevailed over
      the type of lake ecosystems in shaping bacterioplankton diversity.

PMID- 28753496
TI  - Modelling oxygen transfer using dynamic alpha factors.
AB  - Due to the importance of wastewater aeration in meeting treatment requirements
      and due to its elevated energy intensity, it is important to describe the real
      nature of an aeration system to improve design and specification, performance
      prediction, energy consumption, and process sustainability. Because organic
      loadings drive aeration efficiency to its lowest value when the oxygen demand
      (energy) is the highest, the implications of considering their dynamic nature on
      energy costs are of utmost importance. A dynamic model aimed at identifying
      conservation opportunities is presented. The model developed describes the
      correlation between the COD concentration and the alpha factor in activated
      sludge. Using the proposed model, the aeration efficiency is calculated as a
      function of the organic loading (i.e. COD). This results in predictions of oxygen
      transfer values that are more realistic than the traditional method of assuming
      constant alpha values. The model was applied to two water resource recovery
      facilities, and was calibrated and validated with time-sensitive databases. Our
      improved aeration model structure increases the quality of prediction of field
      data through the recognition of the dynamic nature of the alpha factor (alpha) as
      a function of the applied oxygen demand. For the cases presented herein, the
      model prediction of airflow improved by 20-35% when dynamic alpha is used. The
      proposed model offers a quantitative tool for the prediction of energy demand and
      for minimizing aeration design uncertainty.

PMID- 28753497
TI  - Disease-modifying effect of atipamezole in a model of post-traumatic epilepsy.
AB  - Treatment of TBI remains a major unmet medical need, with 2.5 million new cases
      of traumatic brain injury (TBI) each year in Europe and 1.5 million in the USA.
      This single-center proof-of-concept preclinical study tested the hypothesis that
      pharmacologic neurostimulation with proconvulsants, either atipamezole, a
      selective alpha2-adrenoceptor antagonist, or the cannabinoid receptor 1
      antagonist SR141716A, as monotherapy would improve functional recovery after TBI.
      A total of 404 adult Sprague-Dawley male rats were randomized into two groups:
      sham-injured or lateral fluid-percussion-induced TBI. The rats were treated with
      atipamezole (started at 30min or 7 d after TBI) or SR141716A (2min or 30min post
      TBI) for up to 9 wk. Total follow-up time was 14 wk after treatment initiation.
      Outcome measures included motor (composite neuroscore, beam-walking) and
      cognitive performance (Morris water-maze), seizure susceptibility, spontaneous
      seizures, and cortical and hippocampal pathology. All injured rats exhibited
      similar impairment in the neuroscore and beam-walking tests at 2 d post-TBI.
      Atipamezole treatment initiated at either 30min or 7 d post-TBI and continued for
      9 wk via subcutaneous osmotic minipumps improved performance in both the
      neuroscore and beam-walking tests, but not in the Morris water-maze spatial
      learning and memory test. Atipamezole treatment initiated at 7 d post-TBI also
      reduced seizure susceptibility in the pentylenetetrazol test 14 wk after
      treatment initiation, although it did not prevent the development of epilepsy.
      SR141716A administered as a single dose at 2min post-TBI or initiated at 30min
      post-TBI and continued for 9 wk had no recovery-enhancing or antiepileptogenic
      effects. Mechanistic studies to assess the alpha2-adrenoceptor subtype
      specificity of the disease-modifying effects of atipametzole revealed that
      genetic ablation of alpha2A-noradrenergic receptor function in Adra2A mice
      carrying an N79P point mutation had antiepileptogenic effects after TBI. On the
      other hand, blockade of alpha2C-adrenoceptors using the receptor subtype-specific
      antagonist ORM-12741 had no favorable effects on the post-TBI outcome. Finally,
      to assess whether regulation of the post-injury inflammatory response by
      atipametzole in glial cells contributed to a favorable outcome, we investigated
      the effect of atipamezole on spontaneous and/or lipopolysaccharide-stimulated
      astroglial or microglial cytokine release in vitro. We observed no effect. Our
      data demonstrate that a 9-wk administration of alpha2A-noradrenergic antagonist,
      atipamezole, is recovery-enhancing after TBI.

PMID- 28753498
TI  - The impact of epilepsy on academic achievement in children with normal
      intelligence and without major comorbidities: A systematic review.
AB  - PURPOSE: To systematically examine published literature which assessed the
      prevalence of academic difficulties in children with epilepsy (CWE) of normal
      intelligence, and its associating factors. METHODS: A search was conducted on
      five databases for articles published in English from 1980 till March 2015.
      Included were studies who recruited children (aged 5-18 years), with a diagnosis
      or newly/recurrent epilepsy, an intelligent quotient (IQ) of >=70 or attending
      regular school, with or without a control group, which measured academic
      achievement using a standardised objective measure, and published in English.
      Excluded were children with learning difficulties, intellectual disabilities
      (IQ<70) and other comorbidities such as attention deficits hyperactive disorder
      or autism. Two pairs of reviewers extracted the data, and met to resolve any
      differences from the data extraction process. RESULTS: Twenty studies were
      included. The majority of the studies assessed "low achievement" whist only two
      studies used the IQ-achievement discrepancy definition of "underachievement".
      Fourteen studies (70%) reported that CWE had significantly lower academic
      achievement scores compared to healthy controls, children with asthma or reported
      norms. The remaining six studies (30%) did not report any differences. CWE had
      stable academic achievement scores over time (2-4 years), even among those whose
      seizure frequency improved. Higher parental education and children with higher
      IQ, and had better attention or had a positive attitude towards epilepsy, were
      associated with higher academic achievement score. Older children were found to
      have lower academic achievement score. CONCLUSIONS: In CWE of normal
      intelligence, the majority of published literature found that academic
      achievement was lower than controls or reported norms. The high percentages of
      low achievement in CWE, especially in the older age group, and the stability of
      scores even as seizure frequency improved, highlights the need for early
      screening of learning problems, and continued surveillance.

PMID- 28753499
TI  - Non-invasive cardiac output monitoring (NICOM(r)) can predict the evolution of
      uteroplacental disease-Results of the prospective HANDLE study.
AB  - OBJECTIVES: We aimed to firstly identify the different haemodynamic profiles
      amongst nulliparous women who develop either gestational hypertension (GH), pre
      eclampsia (PE), normotensive fetal growth restriction (FGR) versus unaffected
      pregnancies using non-invasive cardiac output monitoring (NICOM(r)). Our second
      primary objective was to assess the ability of NICOM(r) derived variables to
      predict the evolution of PE, GH and FGR. STUDY DESIGN: Low risk nulliparous women
      were enrolled in a single center prospective observational study. NICOM(r)
      assessments were performed at 14, 20 and 28 weeks' gestation and data was
      obtained on cardiac output (CO), total peripheral resistance (TPR), indexed TPR
      (adjusted for maternal body surface area; TPRi), stroke volume (SV), indexed SV
      (adjusted for maternal body surface area; SVi) and heart rate (HR). Logistic
      regression was used to model GH, PE and FGR with NICOM(r) measurements as
      predictors. Linear, non-linear and interaction terms were assessed using the
      Akaike Information Criterion. RESULTS: The haemodynamic profile of pregnancies
      complicated by uteroplacental disease- GH (n=18), PE (n=6) and FGR (n=24) were
      compared to 318 healthy unaffected pregnant controls. Women with evolving PE have
      a different haemodynamic profile to those developing either GH or FGR. The best
      independent predictors for the evolution of uteroplacental disease at 14 weeks'
      gestation were CO in the prediction of FGR (AUC=0.61; p 0.002), TPR in the
      prediction of GH (AUC=0.63; p<0.02) and SVi in the prediction of PE (AUC=0.62;
      p<0.05). The performance of haemodynamic variables was enhanced when combined in
      a multivariate logistic model. We demonstrated that TPR, CO and SV when combined
      with BP were significant predictors of pregnancies complicated by FGR (AUC=0.64,
      p=0.004; AUC=0.65, p=0.004; and AUC=0.65, p=0.007 respectively). Whereas in
      pregnancies complicated by PE, HR and SVi in combination with BP were also
      statistically significant predictors (AUC=0.75, p=0.017 and AUC=0.77, p=0.007
      respectively). CONCLUSIONS: NICOM(r) derived maternal haemodynamic profile at 14
      weeks' gestation has the novel potential to identify pregnancies which will
      ultimately develop uteroplacental disease.

PMID- 28753500
TI  - Laparoscopic, minilaparoscopic, single-port and percutaneous hysterectomy:
      Comparison of perioperative outcomes of minimally invasive approaches in
      gynecologic surgery.
AB  - OBJECTIVES: During the last decade endoscopic surgical procedures have been
      constantly evolving. The latest innovation in ultra-minimally invasive surgery
      (MIS) is the percutaneous technology (PercuvanceTM Percutaneous Surgical System
      (PSS), Teleflex Inc., USA). We compared surgical outcome of hysterectomy, in a
      retrospective cohort study using the most recent MIS techniques as single-site
      (LESS) surgery, 3mm laparoscopy (MiniLPS) and percutaneous system (PSS) with
      standard laparoscopy (LPS). STUDY DESIGN: This is a matched retrospective cohort
      study. Endometrial Hyperplasia/Early stage endometrial cancer or benign pathology
      were the indication for surgery. Data of laparoscopic hysterectomies performed
      between May 2013 and April 2016 using PSS, LPS, MiniLPS, and LESS were collected
      and compared. RESULTS: The characteristics of each group were similar. The median
      Operative time (OT) was significantly longer in LESS compared to all other groups
      (120min [range 55-165] in LESS, 91min [range 60-180] in MiniLPS, 70min [range 55
      230] in LPS and 65 [range 40-180] in PSS; p=0.0001). No significant differences
      among the 4 groups were observed in terms of estimated blood loss, conversion to
      laparoscopy or laparotomy, and intra e post-operative complications.
      Statistically significant differences were recorded in median VAS 24h (2 [range 0
      3] in PSS, 2 [range 0-3] in MiniLPS, 3 [range 2-5] in LESS and 2 [range 1-5] in
      LPS; p=0.0001). The average time of discharge was (1day [range 1-3] in PSS, 1day
      [range 1-2] in MiniLPS, 1days [range 1-2] in LESS and 1day [range 1-3] in LPS;
      p=0.99). CONCLUSIONS: Data show that the effort to minimize the impact of
      surgical invasiveness can be feasible and could improve the advantages, not only
      in terms of aesthetic outcomes, even if the differences among the endoscopic
      approaches have not a relevant clinical impact. The technology innovations like
      PSS maintain the same triangulation between instruments as standard LPS with an
      evident decrease of the invasiveness thanks to reduced instruments size, even if
      the lack of suitability of bipolar energy, that require a multifunction
      instrument, remain a limit of these instruments.

PMID- 28753501
TI  - The effect of active components from citrus fruits on dentin MMPs.
AB  - OBJECTIVES: This study was aimed to evaluate the anti-matrix metalloproteinases
      (MMPs) ability of active components from citrus fruits (hesperetin: Hst,
      hesperidin: Hsd and naringenin: Nge). METHODS: Inactivation effects of citrus
      flavonoids (Hst, Hsd, Nge) at different concentrations on soluble collagenase
      were measured using a fluorometric assay. Matrix-bound endogenous MMPs activity
      was evaluated via dry mass loss and hydroxyproline (HYP) release of demineralized
      human dentin. Demineralized dentin beams were pretreated with 500MUg/mL citrus
      flavonoids for 10min. Chlorhexidine (CHX) was used as inhibitor control. Beams
      pretreated with distilled water served as blank control. Dentin slabs were used
      for in situ zymography and evaluated under confocal microscopy. Ultrastructure of
      demineralized collagen fibers was exhibited by Transmission Electron Microscopy
      (TEM). RESULTS: Citrus flavonoids exhibited inactivation function on soluble MMPs
      and the extent of inactivation increased in a dose-dependent manner. The
      inactivation percent of citrus flavonoids reached above 90% at the concentration
      of 500MUg/mL. Compared with control group, citrus flavonoids pretreated
      demineralized dentin beams exhibited less dry mass loss, lower hydroxyproline
      release and more intact collagen architecture after 15days storage. Dentin
      samples pretreated with citrus flavonoids showed lower enzymes activities in in
      situ zymography. CONCLUSIONS: Hst, Hsd or Nge have anti-MMPs ability and can
      preserve dentin collagen from degradation. CLINICAL SIGNIFICANCE: Hst, Hsd and
      Nge may have the potential to be used in dentin bonding systems and improve the
      resin-dentin bonding durability.

PMID- 28753502
TI  - Isoconversional approach for non-isothermal decomposition of un-irradiated and
      photon-irradiated 5-fluorouracil.
AB  - Kinetic analysis for the non-isothermal decomposition of un-irradiated and photon
      beam-irradiated 5-fluorouracil (5-FU) as anti-cancer drug, was carried out in
      static air. Thermal decomposition of 5-FU proceeds in two steps. One minor step
      in the temperature range of (270-283 degrees C) followed by the major step in the
      temperature range of (285-360 degrees C). The non-isothermal data for un
      irradiated and photon-irradiated 5-FU were analyzed using linear (Tang) and non
      linear (Vyazovkin) isoconversional methods. The results of the application of
      these free models on the present kinetic data showed quite a dependence of the
      activation energy on the extent of conversion. For un-irradiated 5-FU, the non
      isothermal data analysis indicates that the decomposition is generally described
      by A3 and A4 modeles for the minor and major decomposition steps, respectively.
      For a photon-irradiated sample of 5-FU with total absorbed dose of 10Gy, the
      decomposition is controlled by A2 model throughout the coversion range. The
      activation energies calculated in case of photon-irradiated 5-FU were found to be
      lower compared to the values obtained from the thermal decomposition of the un
      irradiated sample probably due to the formation of additional nucleation sites
      created by a photon-irradiation. The decomposition path was investigated by
      intrinsic reaction coordinate (IRC) at the B3LYP/6-311++G(d,p) level of DFT. Two
      transition states were involved in the process by homolytic rupture of NH bond
      and ring secession, respectively.

PMID- 28753503
TI  - Disinfection of various bacterial pathogens using novel silver nanoparticle
      decorated magnetic hybrid colloids.
AB  - Silver nanoparticles (AgNPs) have long been considered a powerful disinfectant
      for controlling pathogenic microorganisms. However, AgNPs might have adverse
      effects on both human health and our ecosystems due to their potential
      cytotoxicity and the difficulty in recovering them after their release into the
      environment. In this study, we characterized the antimicrobial efficacy caused by
      a novel micrometer-sized magnetic hybrid colloid (MHC) containing 7, 15, or 30nm
      sized monodispersed AgNPs (AgNP-MHCs), which can be re-collected from the
      environment using simple procedures, such as a magnet or centrifugation. We
      evaluated the antibacterial capabilities of AgNP-MHCs against target bacteria
      (Legionella pneumophila, Bacillus subtilis, Escherichia coli, and Clostridium
      perfringens) and compared them with the inactivation efficacy of AgNPs ~30nm in
      diameter (nAg30s). Among the different AgNP-MHCs composites evaluated, Ag30-MHCs
      had the greatest antibacterial effect. After 1h of exposure, more than a 4-log10
      reduction of L. pneumophila and 6-log10 reduction of B. subtilis was achieved by
      4.6*109particles/mL of Ag30-MHCs and Ag30-MHC-Ls. In addition, Ag30-MHC-Ls
      maintained their strong antibacterial capabilities under anaerobic conditions.
      Our results indicate that AgNP-MHCs can be considered excellent tools for
      controlling waterborne bacterial pathogens, with a minimal risk of release into
      the environment.

PMID- 28753504
TI  - The roles of cyanobacterial bloom in nitrogen removal.
AB  - Annually occurred cyanobacterial bloom aggravated eutrophication situation and
      changed the lacustrine ecosystem components. Recently, high concentration of
      bloom cyanobacteria had been found to accelerate total nitrogen (TN) removal.
      However, the contribution of cyanobacterial bloom to TN removal remained unclear.
      In this study, microcosms with different density of bloom cyanobacteria were
      constructed and quantitative PCR and structural equation modelling (SEM) were
      used to analyze the microbes, environmental variables and the causal relationship
      to TN removal. Total bacteria, ammonia-oxidizing archaea and nirS gene abundances
      were indirectly influenced by cyanobacteria biomass and all of them had a direct
      effect on TN removal. SEM confirmed that cyanobacteria made a direct contribution
      to ammonium-nitrogen (NH4+-N) level in water and induced nitrification activity,
      which favored the process of denitrification by supplying substrate and
      aggravating the anoxic status. These results strongly suggested that an increased
      cyanobacteria biomass had strong impacts on mineralization, nitrification and
      denitrification by mediating TN, dissolved organic carbon and dissolved oxygen
      directly and subsequently influenced the nitrifiers and denitrifiers.

PMID- 28753505
TI  - First observation of labile arsenic stratification in aluminum sulfate-amended
      sediments using high resolution Zr-oxide DGT.
AB  - Arsenic contamination in sediments has received increasing attention because it
      may be released to the water and threaten aquatic organisms. In this study,
      aluminum sulfate (ALS) was used to immobilize As in sediments through dosage
      series and time-series experiments. Diffusive gradients in thin films (DGT) was
      used to obtain labile As at a vertically 2.0mm resolution. Our results indicated
      that a "static" layer with extremely low labile As concentration (minimally
      0.13mgL-1) with weak variation (<30% RSD) formed within the top 12mm sediment
      layer at the dosage of 6-12ALS/Asmobile (kmolmol-1, Asmobile means the total
      mobile As in top 40mm sediment) and on days 30-80 after amendment at the dosage
      of 9 ALS/Asmobile. The maximum labile As decreased from 1.83 to 0.99MUgL-1 and
      from 1.96 to 1.20MUgL-1 in the dosage-series (3-12 ALS/Asmobile) and time-series
      (10-80days) experiments, respectively, while the depths showing the maximal
      concentrations moved deeper from 22 to 34mm and 20 to 32mm in the sediments. It
      implied a reduced upward diffusion potential of labile As to the static layer in
      deeper sediments. Both distribution coefficient for As between sediment solid
      pool and pore water (Kd) and the adsorption rate constant (k1) consistently
      increased, reflecting that As release from sediment solid became increasingly
      difficult with the progress of ALS immobilization. The results of this millimeter
      scale investigation showed that ALS could efficiently immobilize As in sediments
      under simulated conditions.

PMID- 28753506
TI  - Effect of irrigation and genotypes towards reduction in arsenic load in rice.
AB  - Arsenic (As) bioaccumulation in rice grains has been identified as a major
      problem in Bangladesh and many other parts of the world. Suitable rice genotypes
      along with proper water management practice regulating As levels in rice plants
      must be chosen and implemented. A field study was conducted to investigate the
      effect of continuous flooding (CF) and alternate wetting and drying (AWD)
      irrigation on the bioaccumulation of As in ten rice cultivars at three locations
      having different levels of soil As and irrigation water As. Results showed that
      As concentration in different parts of rice plants varied significantly
      (P<0.0001) with rice genotypes and irrigation practices in the three study
      locations. Lower levels of As in rice were found in AWD irrigation practice
      compared to CF irrigation practice. Higher grain As bioaccumulation was detected
      in plants in areas of high soil As in combination with CF irrigation practice.
      Our data show that use of AWD irrigation practice with suitable genotypes led to
      17 to 35% reduction in grain As level, as well as 7 to 38% increase in grain
      yield. Overall, this study advances our understanding that, for moderate to high
      levels of As contamination, the Binadhan-5, Binadhan-6, Binadhan-8, Binadhan-10
      and BRRI dhan47 varieties were quite promising to mitigate As induced human
      health risk.

PMID- 28753507
TI  - An integrated specification for the nexus of water pollution and economic growth
      in China: Panel cointegration, long-run causality and environmental Kuznets
      curve.
AB  - This paper concentrates on a Chinese context and makes efforts to develop an
      integrated process to explicitly elucidate the relationship between economic
      growth and water pollution discharge-chemical oxygen demand (COD) discharge and
      ammonia nitrogen (NH3-N), using two unbalanced panel data sets covering the
      period separately from 1990 to 2014, and 2001 to 2014. In our present study, the
      panel unit root tests, cointegration tests, and Granger causality tests allowing
      for cross-sectional dependence, nonstationary, and heterogeneity are conducted to
      examine the causal effects of economic growth on COD/NH3-N discharge. Further, we
      simultaneously apply semi-parametric fixed effects estimation and parametric
      fixed effects estimation to investigate environmental Kuznets curve relationship
      for COD/NH3-N discharge. Our empirical results show a long-term bidirectional
      causality between economic growth and COD/NH3-N discharge in China. Within the
      Stochastic Impacts by Regression on Population, Affluence and Technology
      framework, we find evidence in support of an inverted U-shaped curved link
      between economic growth and COD/NH3-N discharge. To the best of our knowledge,
      there have not been any efforts made in investigating the nexus of economic
      growth and water pollution in such an integrated manner. Therefore, this study
      takes a fresh look on this topic.

PMID- 28753508
TI  - Photocatalytic ozonation using doped TiO2 catalysts for the removal of parabens
      in water.
AB  - Conventional wastewater treatments are inefficient for the removal of parabens.
      The aim of this study was finding a suitable solution using ozone and UVA
      irradiation combined with TiO2 catalysts doped with different noble metals (Ag,
      Pt, Pd, Au). Photocatalytic ozonation required lower amounts of ozone for higher
      efficiency on the removal of parabens, chemical oxygen demand (COD) and total
      organic carbon (TOC). The best catalyst for the initial contaminants degradation
      was 0.5% Ag-TiO2 leading to total parabens removal using 46mgO3/L. Due to the
      relative low mineralization achieved, the toxicity of the treated solutions was
      still compared with the initial one over several species (Vibrio fischeri,
      Lepidium sativum and Corbicula fluminea). All the treatments applied led to a
      clear decrease on the toxicity compared with initial mixture of parabens. From an
      economical point of view, it was concluded that the presence of UVA irradiation
      increased the energy consumption compared with catalytic ozonation with these
      catalysts but it can decrease the time of reaction. From the by-products
      analysis, it was concluded that hydroxylation appears to be the most significant
      reaction pathway and the main responsible for parabens degradation.

PMID- 28753509
TI  - Long-term no-tillage and organic input management enhanced the diversity and
      stability of soil microbial community.
AB  - Intensive tillage and high inputs of chemicals are frequently used in
      conventional agriculture management, which critically depresses soil properties
      and causes soil erosion and nonpoint source pollution. Conservation practices,
      such as no-tillage and organic farming, have potential to enhance soil health.
      However, the long-term impact of no-tillage and organic practices on soil
      microbial diversity and community structure has not been fully understood,
      particularly in humid, warm climate regions such as the southeast USA. We
      hypothesized that organic inputs will lead to greater microbial diversity and a
      more stable microbial community, and that the combination of no-tillage and
      organic inputs will maximize soil microbial diversity. We conducted a long-term
      experiment in the southern Appalachian mountains of North Carolina, USA to test
      these hypotheses. The results showed that soil microbial diversity and community
      structure diverged under different management regimes after long term continuous
      treatments. Organic input dominated the effect of management practices on soil
      microbial properties, although no-tillage practice also exerted significant
      impacts. Both no-tillage and organic inputs significantly promoted soil microbial
      diversity and community stability. The combination of no-tillage and organic
      management increased soil microbial diversity over the conventional tillage and
      led to a microbial community structure more similar to the one in an adjacent
      grassland. These results indicate that effective management through reducing
      tillage and increasing organic C inputs can enhance soil microbial diversity and
      community stability.

PMID- 28753510
TI  - Novel techniques for detection and characterization of nanomaterials based on
      aerosol science supporting environmental applications.
AB  - The number of people exposed to nanoparticles is growing accordingly to the
      production and development of new nanomaterials. Moreover, this increase is
      expected to continue in the future. However, there is a lack of standardized
      sampling and metric methods to measure the level of exposure to nanoparticles,
      and the information related to possible adverse health effects is scarce. Aerosol
      technology has been detecting and characterizing nanoparticles for decades and
      some of their developments can be of use in nanotechnology characterization. We
      present here two current developments based on used principles in aerosol
      science, which can widen its application to the characterization of
      nanomaterials. On the one hand, a sample preparation technique for nanoparticle
      analysis by electron microscopy based on electrospray atomization technology.
      Several samples prepared in this way have been analysed and compared to more
      traditional sample preparation strategies like the "drop on grid" method. It was
      found that the particles deposited by electrospray generally show a much more
      homogeneous spatial distribution on the substrate and the number of single
      particles increases substantially. On the other hand, it is presented an
      electrical mobility classification system, DMA, with enormous possibilities for
      the quick and economic size characterization of suspensions of nanoparticles,
      thanks to its injection system by electrospray and to its high resolution in the
      lower range of the nanoscale. The first assessment of the abovementioned devices
      highlights its potential applications in exposure assessment and
      nanotechnological contexts.

PMID- 28753511
TI  - Assessing drugs of abuse distribution in Turia River based on geographic
      information system and liquid chromatography mass spectrometry.
AB  - Drugs of abuse are continuously discharged into wastewaters as part of their
      elimination process. Pollution at very low concentrations appears to be broad in
      environmental compartments near populated areas. A total of 42 drugs of abuse and
      metabolites were analysed in surface water samples collected in 2012 and 2013 by
      solid phase extraction and liquid chromatography coupled to mass spectrometry.
      Analytical results of target compounds were georeferenced and integrated into a
      geographical information systems (GIS). Ecotoxicological risk of drugs of abuse
      detected in the Turia River was evaluated in this study by calculating risk
      quotient (RQ). In 2012, 6 compounds were detected in a total of 22 points. In
      2013, 7 compounds were found in a total of 31 sampling sites, 4 of them also
      detected in 2012. The most frequent compound was benzoylecgonine, detected in 9
      sampling points in 2012 and 8 in 2013, at an average concentration of 25.4ng/L
      and 14.02ng/L. Codeine reached the maximum concentration of detected compounds
      (101ng/L) in 2013. GIS provided the spatial incidence of drugs of abuse along the
      Turia River basin. The distribution of these compounds in 2012 and 2013 shows
      that the highest concentrations and frequency of drugs of abuse run into places
      with the highest population density. The RQ obtained from measured concentrations
      of detected drugs predict that no short-term environmental risk might be
      expected. Further research including multi-stressors studies with more
      potentially persistent or pseudo-persistent organic pollutants in surface waters
      is needed to establish relationships with human pressure in a river basin.

PMID- 28753512
TI  - A new tool for direct non-invasive evaluation of chlorophyll a content from
      diffuse reflectance measurements.
AB  - Chlorophyll is a key biochemical component that is responsible for photosynthesis
      and is an indicator of plant health. The effect of stressors can be determined by
      measuring the amount of chlorophyll a, which is the most abundant chlorophyll, in
      vegetation in general. Nowadays, invasive methods and vegetation indices are used
      for establishing chlorophyll amount or an approximation to this value,
      respectively. This paper demonstrates that H-point curve isolation method (HPCIM)
      is useful for isolating the signal of chlorophyll a from non-invasive diffuse
      reflectance measurements of leaves. Spinach plants have been chosen as an
      example. For applying the HPCIM only the registers of both, a standard and the
      sample are needed. The results obtained by HPCIM and the invasive method were
      statistically similar for spinach leaves: 144+/-6mg/m2 (n=5) and 155+/-40mg/m2
      (n=5), respectively. However, more precise values were achieved with the HPCIM,
      which also involved minimal experimental effort. The HPCIM method was applied to
      spinach plants stressed by the action of several pesticides and water scarcity,
      showing a decrease of chlorophyll a content with time, which is related with a
      loss of health. The results obtained were compared with those achieved by two
      different reflectance vegetation indices (Macc01 and NDVI). Although NDVI and
      HPCIM gave similar footprints for the plants tested, vegetation indices fail in
      the estimation of real content of the chlorophyll a. The HPCIM could contribute
      to improve the knowledge of the chlorophyll a content of vegetation like health
      indicator, by applying it to a much employed non-invasive technique such as
      diffuse reflectance, which can be used in place or in remote sensing mode.

PMID- 28753513
TI  - A mechanism study of airflow rate distribution within the zone of influence
      during air sparging remediation.
AB  - In this study, an improved laboratory two-dimensional airflow visualization
      device was developed for the quantitative analysis of airflow distribution at
      different heights from the sparger (20, 30, and 40cm) within the zone of
      influence (ZOI). The results indicated that the measured airflow rate
      distribution appeared Trapezium when the height was 20cm; however, the airflow
      rate matched a Gaussian distribution when the heights became 30cm and 40cm. The
      conical shape of the ZOI was observed in the experimental processes. The
      experimental results verified that the airflow distribution within the ZOI
      conformed to turbulent jet theory. According to turbulent jet theory, the
      distribution of the airflow rate changes from Trapezium to Gaussian, and the jet
      boundary mixed layer is a linear extension in the processes of jets. Through our
      study, it was found that this theory could be applied to airflow distribution and
      predictive models for the ZOI in air sparging remediation. The shape of the ZOI
      should be cone-like and the boundary layer of the ZOI is a linear extension in
      air sparging process. All the results from this study can provide theoretical
      support for the design and prediction of air sparging remediation for groundwater
      pollution.

PMID- 28753514
TI  - A modified method for pesticide transport and fate in subsurface environment of a
      winter wheat field of Yangling, China.
AB  - The Guanzhong region is one of the water resources shortage areas and also an
      important food producing area in Chinese Loess Plateau. The unreasonable
      application of irrigation and pesticide not only reduces the utilization rate of
      pesticides, but also is a potential threat to aquatic environments. In order to
      explore the reasonable application pattern of irrigation and pesticide, a
      modified method considering crop water requirement and pesticide transport was
      established to simulate transport and fate of Triadimefon in subsurface
      environment of a winter wheat field in Yangling, China. Results indicate that:
      (1) the modified method introduces the concepts of crop water requirement and
      irrigation schedule, which can estimate irrigation amount more accurately and
      achieve the goal of water saving and agricultural diffuse pollution control more
      efficiently. The method shows good potential applications and implications in
      predicting pesticide exposure levels of different crops and in reducing pesticide
      pollution. (2) The changing trends of soil pesticide levels under different
      pesticide applications are various. The Triadimefon concentration level in
      surface soil layer (0.005m) was directly affected by pesticide application and
      irrigation. The Triadimefon peak below the soil depth of 0.035m has prominently
      delayed effects and it is mainly affected by irrigations. The concentration of
      pesticides decays rapidly with the increase of soil depth, and it can be ignored
      below the depth of 0.5m. (3) The soil pesticide levels under different pesticide
      and irrigation modes show considerable differences, the irrigation is still the
      most significant factor affecting the level of soil pesticide residues under
      different time intervals between pesticide application and irrigation. The
      irrigation scheme of one-day interval and five-divided irrigation can effectively
      reduce deep soil pollution without affecting the normal growth of crops. Results
      may provide theoretical basis and guide farmers to choose appropriate irrigation
      and pesticide application patterns.

PMID- 28753515
TI  - Investigation of the association between serum protein concentrations and
      concurrent chronic kidney disease in hyperthyroid cats.
AB  - Our objective was to identify if changes in serum protein concentrations occur in
      hyperthyroidism and to assess their association with the development of azotaemia
      following treatment. Initially non-azotaemic hyperthyroid cats and healthy older
      cats were included. Serum concentrations of protein fractions were determined by
      agarose gel electrophoresis and compared between; hyperthyroid and control cats,
      initially non-azotaemic hyperthyroid cats which developed azotaemia in a 4month
      follow up period (masked-azotaemic) and those which remained non-azotaemic, and
      hyperthyroid cats before and at the time of restoration of euthyroidism. Data are
      presented as median [25th, 75th percentiles]. Hyperthyroid cats (n=56) had higher
      serum alpha2 globulin concentrations (12.5 [10.9, 13.1] g/L vs. 9.8 [3.0, 11.4]
      g/L; P<0.001) and lower serum gamma globulin concentrations (11.4 [9.1, 13.3] g/L
      vs. 14.0 [12.4, 16.8] g/L; P=0.001) than control cats (n=26). Following
      treatment, serum total globulin concentration increased (from 38.6 [35.4, 42.8]
      g/L to 42.3 [39.0, 45.7] g/L; P<0.001), serum alpha2 globulin concentration
      decreased (from 12.5 [10.9, 13.9] g/L to 11.5 [10.1, 12.6] g/L; P<0.001) and
      serum gamma globulin concentration increased (from 11.4 [9.0, 13.3] g/L to 14.0
      [12.4, 16.8] g/L; P<0.001). Serum concentrations of total globulin or globulin
      fractions were not significantly different between masked-azotaemic and non
      azotaemic groups. In conclusion, hyperthyroidism is associated with altered serum
      concentrations of the alpha2 and gamma globulin fractions, however these changes
      were not associated with the development of azotaemic chronic kidney disease
      following treatment.

PMID- 28753516
TI  - Synthesis, molecular modeling studies and bronchodilation properties of
      nicotinonitrile containing-compounds.
AB  - Facile synthetic pathway for nicotinonitriles 5a-o, 7a-i was demonstrated through
      reaction of ketones 4a-k, 6a-f with ylidenemalononitrile 3 in the presence of
      sodium alkoxide. Meanwhile, nucleophilic attack of amines on 2
      bromonicotinonitrile 9 (obtained through reaction of propenone 8 with
      malononitrile, followed by bromination with bromine in acetic acid) afforded 3
      pyridinecarbonitriles 11a-d. Single crystal X-ray of compound 7i reveals the
      monoclinic space group C2/c with 8 molecules per unit cell. Optimized structure
      of 7i [DFT/B3LYP, 6-31G(d,p)] shows close correlations to that of X-ray study.
      Compound 5l seems superior among all the synthesized analogues exhibiting
      bronchodilation properties about three folds potency compared to theophylline
      (standard reference) through pre-contracted tracheal rings with histamine
      standard method. Also compound 5a reveals promising observations (about two folds
      potency of the standard reference). Molecular modeling studies (3D-pharmacophore
      and 2D-QSAR) supported the observed biological properties.

PMID- 28753517
TI  - Design, synthesis and antiproliferative activity of decarbonyl luotonin
      analogues.
AB  - A small library of benzimidazole-fused pyrrolo[3,4-b]quinoline has been
      synthesized from readily available benzimidazole 2-carbaldehyde and various
      substituted arylamines in good to excellent yields utilizing an intramolecular
      Povarov reaction catalyzed by boron trifluoride diethyl etharate as the key final
      step. The compounds thus synthesized can be considered as decarbonyl analogues of
      the anticancer alkaloid luotonin A and were evaluated in a DNA relaxation assay
      for their ability to inhibit human topoisomerase I. Interestingly, two of the
      compounds showed a remarkable activity that is comparable to that of the standard
      drug camptothecin. The compounds were also evaluated for their cytotoxic effect
      in four highly aggressive human cancer cell lines, namely KB, MDA-MB231 (breast),
      LNCap (prostate), and HT1080 (fibrosarcoma). Some of the compounds obtained
      showed promising cytotoxicities for these four cell lines.

PMID- 28753518
TI  - A square peg in a round hole: Theory-practice gap from the lens of Filipino
      student nurses.
AB  - Previous studies suggest that theory-practice gap has remained to be a formidable
      task and a challenge to the nursing profession. While efforts to understand the
      nature and dynamics of theory-practice gap have been undertaken across the globe,
      a dearth in literature exists in the context of a developing country like the
      Philippines. Seemingly, no research has ventured yet to explore the theory
      practice gap experiences of Filipino student nurses. Hence, the major intent of
      this qualitative investigation is to describe and capture how theory-practice gap
      is viewed by a select group of senior nursing students (n=10) in a comprehensive
      university in the Philippines. From the thickness and richness of the
      descriptions of the field text gathered in this study, an interesting
      conceptualization labeled as the Theory-Practice Gap Deficit Triad which consists
      of (a) structural, (b) pedagogical, and (c) relational deficits was emerged.
      Interestingly, the said model describes a clear intersection of the various
      concerns and dilemmas encountered by student nurses in their clinical exposures.
      Findings of this paper are valuable inputs to nursing educators, practitioners,
      and administrators in initiating realignment efforts geared toward developing
      nurses whose knowledge, skills and attitudes are responsive to the ever changing
      professional practice landscape.

PMID- 28753519
TI  - Enantioselectivity of anteiso-fatty acids in hitherto uninspected sample
      matrices.
AB  - Anteiso-fatty acids (aFAs) are chiral molecules due to a methyl substituent on
      the antepenultimate carbon of the otherwise straight acyl chain. 12
      Methyltetradecanoic acid (a15:0) and 14-methylhexadecanoic acid (a17:0) are the
      predominant aFAs in nature but their individual contributions e.g. to food lipids
      are usually low. Enantioselective data has been collected in fish, bovine
      milk/cheese, and Brussels sprouts. In this study, we determined the
      enantioselectivity of a15:0 and a17:0 in shea butter, moose and camel milk, two
      soil samples and mold (collected from contaminated cheese). For this purpose,
      sample lipids were extracted and containing fatty acids were converted into
      methyl esters. Methyl esters of aFAs were selectively enriched by hydrogenation,
      urea complexation and/or RP-HPLC-fractionation. Enantioselective gas
      chromatography with mass spectrometry operated in the selected ion monitoring
      mode using a chiral stationary phase consisting of 66% tert.
      butyldimethylsilylated beta-cyclodextrin in OV-1701. While a15:0 and a17:0 in
      moose milk were (S)-enantiopure, all other determined samples contained up to 10%
      (R)-aFAs. The highest proportions of (R)-enantiomers were detected in the soil
      samples (ee=80%).

PMID- 28753520
TI  - Interleukin-10 inhibits neuroinflammation-mediated apoptosis of ventral
      mesencephalic neurons via JAK-STAT3 pathway.
AB  - Neuroinflammation plays an important role in the pathogenesis of Parkinson's
      disease. Interleukin (IL)-10 is one of the most important and best anti
      inflammatory cytokines. The objective of this report is to investigate whether IL
      10 has any role in protecting ventral mesencephalic (VM) neurons in in vitro
      model of neuroinflammation. In this study, primary neuron-enriched culture was
      prepared from the VM tissues of E14 embryos of rats. The cells were pretreated
      with IL-10 (15 or 50ng/mL) for 1h followed by lipopolysaccharide (LPS, 50ng/mL)
      application. We found LPS induced neuronal apoptosis and loss while pretreatment
      with IL-10 reduced neuronal damage after exposure of LPS toxicity. Furthermore,
      signal transduction pathways related to IL-10 in VM neurons were studied in
      inflammatory condition. We used both shRNA and pharmacologic inhibition to
      determine the role of the IL-10 receptor (IL-10R) and its downstream signaling
      pathways in LPS-induced VM neuronal toxicity. Silence of the IL-10R gene in VM
      neurons abolished IL-10 mediated protection and the properties of anti
      inflammatory and anti-apoptosis. IL-10 also induced phosphorylation of signal
      transducer and activator of transcription (STAT) 3 in VM neurons. Pretreatment
      with the specific Janus kinase (JAK) inhibitor reduced STAT3 phosphorylation and
      blocked IL-10 mediated protection against LPS. These findings suggest that IL-10
      provides neuroprotection by acting via IL-10R and its down-stream JAK-STAT3
      signal pathways in VM neurons.

PMID- 28753521
TI  - Comparing electro- and mechano-myographic muscle activation patterns in self
      paced pediatric gait.
AB  - Electromyography (EMG) is the standard modality for measuring muscle activity.
      However, the convenience and availability of low-cost accelerometer-based
      wearables makes mechanomyography (MMG) an increasingly attractive alternative
      modality for clinical applications. Literature to date has demonstrated a strong
      association between EMG and MMG temporal alignment in isometric and isokinetic
      contractions. However, the EMG-MMG relationship has not been studied in gait. In
      this study, the concurrence of EMG- and MMG-detected contractions in the tibialis
      anterior, lateral gastrocnemius, vastus lateralis, and biceps femoris muscles
      were investigated in children during self-paced gait. Furthermore, the
      distribution of signal power over the gait cycle was statistically compared
      between EMG-MMG modalities. With EMG as the reference, muscular contractions were
      detected based on MMG with balanced accuracies between 88 and 94% for all muscles
      except the gastrocnemius. MMG signal power differed from that of EMG during
      certain phases of the gait cycle in all muscles except the biceps femoris. These
      timing and power distribution differences between the two modalities may in part
      be related to muscle fascicle length changes that are unique to muscle motion
      during gait. Our findings suggest that the relationship between EMG and MMG
      appears to be more complex during gait than in isometric and isokinetic
      contractions.

PMID- 28753522
TI  - Bio-affinity of copper(II) complexes with nitrogen and oxygen donor ligands:
      Synthesis, structural studies and in vitro DNA and HSA interaction of copper(II)
      complexes.
AB  - Reported herein the binding affinity between Human Serum Albumin and the DNA
      binding and cleavage activity of three copper(II) complexes, [Cu(phen)(o
      van)ClO4] (1), [Cu(phen)(gly)]ClO4 (2) and [Cu(L1)2(H2O)2] (3) wherein 1 and 2
      are synthesized with 1,10-phenanthroline (phen) and co-ligands (o-van: o
      vanillin; gly: glycine) and 3 with a ligand 2-hydroxy-3-methoxybenzylidene-4H
      1,2,4-triazol-4-amine (H1L1). Complex 2 crystallizes in monoclinic (P21/n) space
      group shows square pyramidal geometry. The complex 3 crystallizes in monoclinic
      (P21/a) space group. All the three complexes exhibit binding affinity towards the
      transport protein Human Serum albumin (HSA). Quantitative evaluation of the
      thermodynamics of interaction and the results obtained from fluorescence
      spectroscopy suggest that metal coordinated glycynate, o-vanillin and perchlorate
      groups have a major role to play in the binding process, the latter two being
      stronger in the binding of complex 1. The coordinated water in complex 3 also
      plays an important role in the binding, which makes binding of complex 3 with HSA
      stronger than that of complex 2. Experimental results indicate that the binding
      affinity of the complexes towards CT-DNA is in the order 1>3>2 implying that
      complex 1 binds stronger than complex 3 and 2.The DNA cleaving activity of all
      the three complexes was explored in the presence of reactive oxygen compound,
      H2O2. All the three complexes have primarily shown the DNA cleaving activity.

PMID- 28753523
TI  - Development and in vitro assessment of psoralen and resveratrol co-loaded
      ultradeformable liposomes for the treatment of vitiligo.
AB  - Vitiligo is a de-pigmenting skin disorder characterized by white patches on skin
      due to partial or complete loss of melanocytes. Psoralen in combination with
      ultraviolet-A (PUVA) acts by stimulation of melanin content and tyrosinase
      activity in melanocytes. Resveratrol, a sirtuin activator and a potential anti
      oxidant reduce oxidative stress which is one of the triggering factors for
      initiation of vitiligo. Despite their therapeutic activity, weak percutaneous
      permeability of psoralen and poor solubility of resveratrol hinders their
      effective topical administration. The aim of present study is to formulate
      ultradeformable liposomes (UDL) co-loaded with psoralen and resveratrol for
      evaluation of PUVA and anti-oxidant combination in vitiligo treatment. For this
      purpose, UDL composed of DC-Chol, cholesterol and sodium deoxy cholate were
      prepared for their co-delivery. Liposomal carriers were characterized and
      evaluated for their efficacy using B16F10 cell line. Free radical scavenging
      potential was also determined for these carriers by in vitro anti-oxidant assays.
      Optimal co-loaded UDL with particle size ranging from 120 to 130nm, zeta
      potential of +46.2mV, entrapment efficiency of 74.09% (psoralen) and 76.91%
      (resveratrol) were obtained. Compared to control, co-loaded UDL showed
      significant stimulation of melanin and tyrosinase activity with major
      contribution of psoralen. Further, co-loaded UDL also exhibited potential free
      radical scavenging activity where resveratrol played a key role. Hence, psoralen
      and resveratrol co-loaded UDL acts in vitiligo through dual mechanisms of action
      viz., stimulation of melanin and tyrosinase activity as well as by anti-oxidant
      activity. These findings indicate that psoralen and resveratrol co-loaded UDL has
      the promising therapeutic potential for the treatment of vitiligo.

PMID- 28753525
TI  - Implications of quenching in efficiency, spectrum shape and alpha/beta
      separation.
AB  - Liquid scintillation spectrometry (LSS) is a meaningful technique for the
      determination of alpha and beta emitters. However, this technique is highly
      affected by quenching phenomena, which reduce the counting efficiency, shift the
      spectra to low energies and cause misclassification problems. In this paper, a
      selection of chemical and colour quench agents was evaluated to study the
      influence of alpha and beta energy and the quenching effect on the detection
      efficiency, the shape of the spectra and the alpha/beta misclassification.

PMID- 28753524
TI  - Park availability and major depression in individuals with chronic conditions: Is
      there an association in urban India?
AB  - Green space exposure has been positively correlated with better mental-health
      indicators in several high income countries, but has not been examined in low-
      and middle-income countries undergoing rapid urbanization. Building on a study of
      mental health in adults with a pre-existing chronic condition, we examined the
      association between park availability and major depression among 1208 adults
      surveyed in Delhi, India. Major depression was measured using the Mini
      International Neuropsychiatric Interview. The ArcGIS platform was used to
      quantify park availability indexed as (i) park distance from households, (ii)
      area of the nearest park; and within one km buffer area around households - the
      (iii) number and (iv) total area of all parks. Mixed-effects logistic regression
      models adjusted for socio-demographic characteristics indicated that relative to
      residents exposed to the largest nearest park areas (tertile 3), the odds [95%
      confidence interval] of major depression was 3.1 [1.4-7.0] times higher among
      residents exposed to the smallest nearest park areas (tertile 1) and 2.1 [0.9
      4.8] times higher in residents with mid-level exposure (tertile 2). There was no
      statistically significant association between other park variables tested and
      major depression. We hypothesized that physical activity in the form of walking,
      perceived stress levels and satisfaction with the neighborhood environment may
      have mediating effects on the association between nearest park area and major
      depression. We found no significant mediation effects for any of our hypothesized
      variables. In conclusion, our results provide preliminary and novel evidence from
      India that availability of large parks in the immediate neighborhood positively
      impacts mental well-being of individuals with pre-existing chronic conditions, at
      the opportune time when India is embarking on the development of sustainable
      cities that aim to promote health through smart urban design - one of the key
      elements of which is the inclusion of urban green spaces.

PMID- 28753526
TI  - Influence of maternal and sociodemographic characteristics on the accumulation of
      organohalogen compounds in Argentinian women. The EMASAR study.
AB  - The occurrence of organohalogen compounds in venous serum from post-partum
      mothers from two Argentinian cities, Salta and Ushuaia, has been investigated (n
      = 698). 4,4'-DDE was the most abundant compound in these cities, with geometric
      means of 33 and 67ng/g lipid weight, respectively. City of residence, age and
      parity were the main determinants of the accumulation of these compounds.
      Hexachlorobenzene (HCB) was the second most abundant pollutant in Ushuaia,
      8.7ng/g lipid, and beta-hexachlorocyclohexane (beta-HCH) in Salta, 7.8ng/g lipid.
      Decabromodiphenyl ether was higher in Ushuaia than Salta, 8.2 and 4.1ng/g lipid,
      respectively. The predominance of beta-HCH, 4,4'-DDE and 4,4'-DDT in Salta was
      related with higher use of pesticides for agricultural applications. The observed
      higher concentrations of 4,4'-DDE and 4,4'-DDT in the mothers from rural+semi
      urban sites than in urban areas were consistent with this agricultural origin. In
      addition, the most volatile organochlorine compounds included in this study, HCB
      and alpha-HCH, were mainly found in Ushuaia. The concentrations of the studied
      organohalogen pollutants in Argentina were lower than those found in other
      similar studies which is consistent with the location of these cities in the
      southern hemisphere. Age, mainly for 4,4'-DDE and polychlorobiphenyl (PCB)
      congeners 138, 153 and 180, and parity, mainly for HCB, beta-HCH, 4,4'-DDT and
      PCB congener 118, were the second main determinants of the concentrations of
      these compounds. Gestational weight gain also influenced on the maternal levels
      of HCB, beta-HCH, 4,4'-DDT and PCB congeners 118, 138 and 153. Higher weight
      accumulation during pregnancy involved dilution of these persistent pollutants.
      Body mass index (BMI) was a statistically significant determinant for 4,4'-DDT,
      alpha-HCH and PCB congeners 153 and 180. The observed direct correspondence
      between higher BMI and 4,4'-DDT concentrations was in agreement with the above
      reported inputs related with agricultural applications. The reverse
      correspondence of BMI with alpha-HCH and the PCB congeners indicated higher
      dilution at higher weight increase.

PMID- 28753527
TI  - Incubation lighting schedules and their interaction with matched or mismatched
      post hatch lighting schedules: Effects on broiler bone development and leg health
      at slaughter age.
AB  - The incidence of leg pathologies in broiler chickens with a developmental origin
      may be decreased by stimulating embryonic bone development through lighting
      schedules during incubation, but this may depend on post hatch lighting
      conditions. Aim was to investigate how lighting schedules during incubation and
      their interactions with matched or mismatched lighting schedules post hatch
      affected bone development and leg health at slaughter age. In a 3*2 factorial
      designed experiment, eggs were incubated under continuous cool white LED light
      (Inc24L), 16h of light, 8h of darkness (Inc16L:8D), or continuous darkness
      (Inc24D) from set till hatch. After hatch, broilers were housed under continuous
      light (PH24L, to match Inc24L and Inc24D) or 16h of light, 8h of darkness
      (PH16L:8D, to match Inc16L:8D). Gait scores were determined on D21, D28, and D34.
      After slaughter on D35, legs were scored for varus-valgus deformities, rotated
      tibia, tibial dyschondroplasia, bacterial chondronecrosis with osteomyelitis
      (BCO), epiphyseolysis, and epiphyseal plate abnormalities from 1=absent to
      4=severe. Femur and tibia dimensions and mineral density were determined. Inc24L
      led to more epiphyseal plate abnormalities than Inc16L:8D or Inc24D. Inc24D led
      to more BCO than Inc16L:8D. Gait scores on D21, D28, and D34, and bone dimensions
      did not differ between treatments. Inc24L led to higher femur mineral density
      than Inc24D with Inc16L:8D intermediate. Providing a chicken with a matched post
      hatch lighting schedule did not affect most measurements of bone development and
      health. It can be concluded that a circadian incubation lighting schedule may
      improve leg health in broilers.

PMID- 28753528
TI  - Microheterogeneity in CH3OH/CD3OH mixture.
AB  - Recently, we demonstrated the presence of microheterogeneity in binary mixtures
      of unlike alcohols. [RSC Adv. 2016, 6, 37195-37202] The aim of this work was
      examination if this phenomenon occurs also in the mixture of very similar
      alcohols like CH3OH and CD3OH. Theoretical calculations suggest that the isotopic
      substitution in methyl group influences properties of the OH group. Hence, one
      can expect that this effect may lead to partial separation of CH3OH and CD3OH at
      a molecular level and it contributes to deviation from the ideal mixture. This
      work evidences that CH3OH/CD3OH mixture also deviates from the ideal one, but the
      extent of this deviation is much smaller as compared with the mixtures of other
      alcohols. It is of particular note that this deviation results mainly from the
      difference between the CH3 and CD3 groups, while the contribution from the OH
      groups is small. The structure of CH3OH/CD3OH mixture at a molecular level is
      similar to the structure of binary mixtures of other alcohols. The mixture is
      composed of the homoclusters of both alcohols and the mixed clusters. The
      homoclusters existing in the mixture are similar to those present in bulk
      alcohols. The highest population of the heteroclusters and the largest deviation
      from the ideal mixture were observed at equimolar mixture. Both the experimental
      and theoretical results reveal that in CH3OH/CD3OH mixture dominate the cyclic
      tetramers and larger clusters, while the population of the linear clusters is
      negligible. Though the extent and strength of hydrogen bonding in both alcohols
      are the same, the position and intensity of the 2nu(OH) band for CH3OH and CD3OH
      are different. We propose possible explanation of this observation.

PMID- 28753529
TI  - UV absorbers for cellulosic apparels: A computational and experimental study.
AB  - Two triazine based Ultra Violet (UV) absorbers Sulfuric acid mono-(2-{4-[4-chloro
      6-(4-{4-chloro-6-[4-(2-sulfooxy-ethanesulfonyl)-phenylamino]-[1,3,5] triazin-2
      ylamino-phenylamino)-[1,3,5]triazin-2-ylamino]-benzenesulfonyl}-ethyl) ester (1a)
      and 4-{4-chloro-6-[4-(2-sulfooxy-ethanesulfonyl)-phenylamino]-[1,3,5] triazin-2
      ylamino}-2-[4-chloro-6-(2-sulfooxy-ethanesulfonyl)-[1,3,5]triazin-2-ylamino]
      benzenesulfonic acid (2a) with different substituents were designed
      computationally. The influence of different substituents on the electrochemical
      properties and UV spectra of the absorbers was investigated. The presence of
      electron deficient unit in 1a to the molecular core significantly reduces the
      LUMO levels and energy gap. The designed absorbers were synthesized via
      condensation reaction and characterized by UV-Vis, FT-IR, MS studies. The
      performance of synthesized compounds as UV absorbers and their fastness
      properties were assessed by finishing the cotton fabric through exhaust method at
      different concentration and results appeared in good range.

PMID- 28753530
TI  - Multi-spectroscopic and molecular modeling approaches to elucidate the binding
      interaction between bovine serum albumin and darunavir, a HIV protease inhibitor.
AB  - Darunavir (DRV), a second-generation HIV protease inhibitor, is widely used
      across the world as an important component of HIV therapy. The interaction of DRV
      with bovine serum albumin (BSA), a major carrier protein, has been studied under
      simulated physiological conditions (pH7.4) by multi-spectroscopic techniques in
      combination with molecular modeling. Fluorescence data revealed that the
      intrinsic fluorescence of BSA was quenched by DRV in terms of a static quenching
      procedure due to the formation of the DRV-BSA complex. The results indicated the
      presence of single weak affinity binding site (~103M-1, 310K) on protein. The
      thermodynamic parameters, namely enthalpy change (DeltaH0), entropy change
      (DeltaS0) and Gibbs free energy change (DeltaG0) were calculated, which signified
      that the binding reaction was spontaneous, the main binding forces were hydrogen
      bonding and van der Waals forces. Importantly, competitive binding experiments
      with three site probes, phenylbutazone (in sub-domain IIA, site I), ibuprofen (in
      sub-domain IIIA, site II) and artemether (in the interface between sub-domain IIA
      and IIB, site II'), suggested that DRV was preferentially bound to the
      hydrophobic cavity in site II' of BSA, and this finding was validated by the
      docking results. Additionally, synchronous fluorescence, three-dimensional
      fluorescence and Resonance Rayleigh Scattering (RRS) spectroscopy gave
      qualitative information on the conformational changes of BSA upon adding DRV,
      while quantitative data were obtained with Fourier transform infrared
      spectroscopy (FT-IR).

PMID- 28753531
TI  - Dengue virus infection during pregnancy increased the risk of adverse fetal
      outcomes? An updated meta-analysis.
AB  - OBJECTIVE: To evaluate the effect of maternal dengue virus (DENV) infection
      during pregnancy in premature birth, low birth weight, miscarriage and
      stillbirth. METHODS: Systematic electronic literature searches were conducted
      including PubMed, Medline, Embase, Web of science, Scopus and the Cochrane
      Library database, up until July 5, 2017. Effect sizes were estimated by using the
      relative risk (RR) or odds ratio (OR) with theirs corresponding 95% confidence
      interval (CI). Subgroup analyses were conducted for study design (prospective or
      retrospective) and clinical symptom of participants (symptomatic or
      asymptomatic). Statistical analysis was conducted by STATA 12.0. RESULTS: The
      initial systematic literature searches identified 1048 studies. After screening,
      fourteen studies were included. The pooled results did not suggest maternal DENV
      infection might increase the risk of adverse fetal outcomes with a pooled RR of
      0.96 (95% CI: 0.85-1.09, I2=49.6%) for premature birth, RR of 0.99 (95%CI: 0.87
      1.12, I2=35.1%) for low birth weight, OR of 1.77 (95% CI: 0.99-3.15, I2=17.5%)
      for miscarriage and RR of 3.42 (95% CI: 0.76-15.49, I2=54.8%) for stillbirth.
      Subgroup analysis of studies in symptomatic participants still did not indicate
      DENV infection appeared to be a risk factor for premature birth, low birth weight
      and miscarriage with pooled effect size of 0.99 (95% CI: 0.87-1.13, I2=49.3%),
      1.22 (95% CI: 0.827-1.80, I2=55.1%) and 1.19 (95% CI: 0.56-2.55, I2=4.7%),
      respectively. CONCLUSIONS: Current evidence did not suggest that maternal DENV
      infection during pregnancy might increase the risk of premature birth, low birth
      weight, miscarriage and stillbirth.

PMID- 28753532
TI  - The longitudinal association between informal caregiving and body mass index in
      the second half of life: findings of the German Ageing Survey.
AB  - OBJECTIVE: We aimed to investigate the relation between informal caregiving and
      body mass index (BMI) longitudinally. STUDY DESIGN: The data were drawn from wave
      2 (2002) to wave 5 (2014) of the German Ageing Survey. This is a representative
      sample of the community-dwelling population aged 40 years and above in Germany.
      METHODS: Self-rated BMI was used. Individuals were asked whether they provide
      informal care on a regular basis. Adjusting for employment status, age, marital
      status, morbidity and depressive symptoms, fixed effects regressions were used.
      RESULTS: The fixed effects regressions showed that the onset of informal
      caregiving was not associated with changes in BMI in the total sample and in
      women, whereas the onset of informal caregiving was associated with increasing
      BMI in men (beta = 0.15, P < 0.05). In addition, an increase in BMI was
      positively associated with ageing, an increase in morbidity and a decrease in
      frequency of sports activities in the total sample and in both sexes.
      CONCLUSIONS: Our findings stress the longitudinal relation between informal
      caregiving and BMI in men. Consequently, it might be helpful to generate weight
      management strategies specifically designed for male informal caregivers.

PMID- 28753533
TI  - Role of TRAF3 in neurological and cardiovascular diseases: an overview of recent
      studies.
AB  - Tumour necrosis factor receptor-associated factor 3 (TRAF3) is a member of the
      TRAF adaptor protein family, which exerts different effects on the cell depending
      on the receptor to which it binds and the cell type in which it is expressed.
      TRAF3 is a major regulator of the innate immune response. To perform its
      functions properly, TRAF3 is transcriptionally and epigenetically regulated. At
      the transcriptional level, TRAF3 expression has been associated with neurological
      and cardiovascular diseases including stroke, among other pathologies. Epigenetic
      modifications of TRAF3 have been observed at the histone and DNA levels. It has
      been observed that acetylation of TRAF3, as well as other NF-kappabeta target
      genes, is associated with cardiac hypertrophy. Furthermore, TRAF3 methylation has
      been associated with vascular recurrence after ischemic stroke in patients
      treated with clopidogrel. In this overview, we summarise the most interesting
      studies related to transcriptional and epigenetic regulation of TRAF3 focusing on
      those studies performed in neurological and cardiovascular diseases.

PMID- 28753534
TI  - Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and
      circulating tumor DNA.
AB  - Ovarian cancer remains the most lethal disease among gynecological malignancies
      despite the plethora of research studies during the last decades. The majority of
      patients are diagnosed in an advanced stage and exhibit resistance to standard
      chemotherapy. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)
      represent the main liquid biopsy approaches that offer a minimally invasive
      sample collection. Both have shown a diagnostic, prognostic and predictive value
      in many types of solid malignancies and recent studies attempted to shed light on
      their role in ovarian cancer. This review is mainly focused on the clinical value
      of both CTCs and ctDNA in ovarian cancer and, more specifically, on their
      potential as diagnostic, prognostic and predictive tumor biomarkers.

PMID- 28753535
TI  - The risk of unjustified BRCA testing after the "Angelina Jolie effect": how can
      we save (laboratory) medicine from the Internet?

PMID- 28753536
TI  - Generalized Correlation Coefficient for Non-Parametric Analysis of Microarray
      Time-Course Data.
AB  - Modeling complex time-course patterns is a challenging issue in microarray study
      due to complex gene expression patterns in response to the time-course
      experiment. We introduce the generalized correlation coefficient and propose a
      combinatory approach for detecting, testing and clustering the heterogeneous time
      course gene expression patterns. Application of the method identified nonlinear
      time-course patterns in high agreement with parametric analysis. We conclude that
      the non-parametric nature in the generalized correlation analysis could be an
      useful and efficient tool for analyzing microarray time-course data and for
      exploring the complex relationships in the omics data for studying their
      association with disease and health.

PMID- 28753537
TI  - Comparison of Different Approaches for Measuring Tibial Cartilage Thickness.
AB  - Osteoarthritis is a degenerative disease affecting bones and cartilage especially
      in the human knee. In this context, cartilage thickness is an indicator for knee
      cartilage health. Thickness measurements are performed on medical images acquired
      in-vivo. Currently, there is no standard method agreed upon that defines a
      distance measure in articular cartilage. In this work, we present a comparison of
      different methods commonly used in literature. These methods are based on nearest
      neighbors, surface normal vectors, local thickness and potential field lines. All
      approaches were applied to manual segmentations of tibia and lateral and medial
      tibial cartilage performed by experienced raters. The underlying data were
      contrast agent-enhanced cone-beam C-arm CT reconstructions of one healthy
      subject's knee. The subject was scanned three times, once in supine position and
      two times in a standing weight-bearing position. A comparison of the resulting
      thickness maps shows similar distributions and high correlation coefficients
      between the approaches above 0.90. The nearest neighbor method results on average
      in the lowest cartilage thickness values, while the local thickness approach
      assigns the highest values. We showed that the different methods agree in their
      thickness distribution. The results will be used for a future evaluation of
      cartilage change under weight-bearing conditions.

PMID- 28753538
TI  - Improving the Quality of Positive Datasets for the Establishment of Machine
      Learning Models for pre-microRNA Detection.
AB  - MicroRNAs (miRNAs) are involved in the post-transcriptional regulation of protein
      abundance and thus have a great impact on the resulting phenotype. It is,
      therefore, no wonder that they have been implicated in many diseases ranging from
      virus infections to cancer. This impact on the phenotype leads to a great
      interest in establishing the miRNAs of an organism. Experimental methods are
      complicated which led to the development of computational methods for pre-miRNA
      detection. Such methods generally employ machine learning to establish models for
      the discrimination between miRNAs and other sequences. Positive training data for
      model establishment, for the most part, stems from miRBase, the miRNA registry.
      The quality of the entries in miRBase has been questioned, though. This unknown
      quality led to the development of filtering strategies in attempts to produce
      high quality positive datasets which can lead to a scarcity of positive data. To
      analyze the quality of filtered data we developed a machine learning model and
      found it is well able to establish data quality based on intrinsic measures.
      Additionally, we analyzed which features describing pre-miRNAs could discriminate
      between low and high quality data. Both models are applicable to data from
      miRBase and can be used for establishing high quality positive data. This will
      facilitate the development of better miRNA detection tools which will make the
      prediction of miRNAs in disease states more accurate. Finally, we applied both
      models to all miRBase data and provide the list of high quality hairpins.

PMID- 28753539
TI  - Clinical features and genotyping of patients with primary carnitine deficiency
      identified by newborn screening.
AB  - BACKGROUND: The objective of the study was to investigate clinical and gene
      mutation characteristics of primary carnitine deficiency (PCD) patients
      identified by newborn screening using tandem mass spectrometry (MS/MS). METHODS:
      Tandem mass spectrometry (MS/MS) was applied to screen inherited metabolic
      disease and seven patients with PCD were diagnosed among 62,568 samples. The
      SLC22A5 gene was detected by using diagnosis panel of genetic and metabolic
      diseases based on Ion Torrent Semiconductor Sequencing Technology. RESULTS: The
      initial free carnitine (C0) concentrations of the patients were 6.43+/-1.36
      MUmol/L, and the recall screening concentrations were 5.59+/-0.89 MUmol/L. The
      patients were treated with oral carnitine, so the levels after treatment were
      20.24+/-3.88 MUmol/L. All patients had two pathogenic mutation alleles.
      CONCLUSIONS: The combined application of MS/MS and a next generation sequencing
      panel could be used for the accurate diagnosis of PCD. The results of genetic
      diagnosis can guide the assisted reproductive treatment. The prognosis of PCD
      patients is good after early treatment.

PMID- 28753540
TI  - Partial clinical remission in type 1 diabetes: a comparison of the accuracy of
      total daily dose of insulin of <0.3 units/kg/day to the gold standard insulin
      dose adjusted hemoglobin A1c of <=9 for the detection of partial clinical
      remission.
AB  - BACKGROUND: It is unclear whether the gold standard test for the detection of
      partial clinical remission (PCR) in new-onset type 1 diabetes (T1D), the insulin
      dose adjusted Hemoglobin A1c (IDAA1c) of <=9, is superior to a new tool, total
      daily dose of insulin (TDD) of <0.3 units/kg/day. The aim of the study was to
      test the superiority of IDAA1c over TDD of <0.3 units/kg/day for the detection of
      PCR. METHODS: A retrospective analysis of 204 subjects of ages 2-14 years, mean
      age 7.9+/-3.2 years, (male 7.8+/-3.4 years, [n=98]; female 7.9+/-3.0 years,
      [n=106], p=0.816) with new-onset T1D. Anthropometric and biochemical data were
      collected for the first 36 months of disease. PCR was defined by both IDAA1c<=9
      and TDD<0.3 units/kg/day. RESULTS: There were 86 (42.2%) (age 9.1+/-3.0 years;
      male 57%) remitters by IDAA1c<=9 criterion, and 82 (40.2%) remitters (age 7.3+/
      2.8 years) by TDD of <0.3 units/kg/day criterion (p=0.655). The duration of PCR
      was 10.0+/-6.1 months using TDD<0.3 units/kg/day, and 9.2+/-5.5 months using
      IDAA1c (p=0.379). Subjects in PCR as denoted by TDD<0.3 units/kg/day had 1.44
      times increased probability of entering PCR than those denoted by IDAA1c of <=9,
      after adjusting for BMI, bicarbonate, and HbA1c:(OR=1.44, 95% CI [1.03-2.00],
      p=0.033). Peak prevalence for PCR was at 6-12 months by either definition; more
      subjects were in PCR at 6 months by IDAA1c <=9: 62/86 (72.1%) than by TDD<0.3
      units/kg/day: 43/82 (52.4%), (p=0.011). CONCLUSIONS: There were no significant
      differences in the number of remitters, duration of PCR, or the time of peak
      remission defined by IDAA1c of <=9 or TDD of <0.3 units/kg/day.

PMID- 28753541
TI  - Health-related quality of life among children with Turner syndrome: controlled
      cross-sectional study.
AB  - BACKGROUND: The aim of the study was to assess health-related quality of life (HR
      QoL) in children with Turner syndrome in comparison with controls. METHODS: We
      prospectively recruited 16 female girls with Turner syndrome (mean age 15.2+/-2.6
      years) and 78 female controls (mean age 12.7+/-2.8 years) in randomly selected
      schools. We used the PedsQL, a generic HR-QoL questionnaire (self and parents'
      versions). RESULTS: Global HR-QoL scores in Turner syndrome were lower than
      controls for self-reports (respectively, 74.3+/-3.0 vs. 82.8+/-1.3, p=0.01) and
      parents' reports (62.7+/-3.8 vs. 80.1+/-1.7, p<0.0001). In Turner syndrome, self
      reported HR-QoL was impaired in school functioning (70.6+/-4.0 vs. 80.71+/-1.7,
      p=0.02), social functioning (78.2+/-4.0 vs. 90.4+/-1.8, p<0.01) and physical
      functioning (78.5+/-3.2 vs. 87.1+/-1.4, p=0.02), but not in emotional
      functioning. Parents' reported HR-QoL was impaired in all four dimensions.
      CONCLUSIONS: HR-QoL was impaired in this cohort of young females with Turner
      syndrome, as in previously reported adult studies. In addition to medical
      treatment and routine clinical follow-up, female girls and teenagers with Turner
      syndrome should also be supported psychologically by social, educational and
      psychotherapeutic interventions that aim to address their self-esteem and
      emotional difficulties.

PMID- 28753542
TI  - MRI in medium-chain acyl-coenzyme a dehydrogenase deficiency: neuroimaging during
      the first month.
AB  - BACKGROUND: Medium-chain acyl-coenzyme A dehydrogenase (MCAD) is the most common
      genetic disorder of fatty acid oxidation, which presents before the age of 2 with
      the onset of acute hypoketotic hypoglycemia, and is typically precipitated by
      stress. CASE PRESENTATION: We report serial brain magnetic resonance imaging
      (MRI) changes, including MR spectroscopy (MRS) and diffusion weighted imaging
      (DWI), in a patient with a classical MCAD presentation, compared with five
      healthy controls. CONCLUSIONS: Through this unique case we analyze the evolution
      of radiological findings during the first month of illness and we highlight the
      pivotal role of MRI, especially DWI, in the early diagnosis of the decompensated
      state of the disease.

PMID- 28753543
TI  - NLRP genes and their role in preeclampsia and multi-locus imprinting disorders.
AB  - Preeclampsia (PE) affects 2-5% of all pregnancies. It is a multifactorial
      disease, but it has been estimated that 35% of the variance in liability of PE
      are attributable to maternal genetic effects and 20% to fetal genetic effects. PE
      has also been reported in women delivering children with Beckwith-Wiedemann
      syndrome (BWS, OMIM 130650), a disorder associated with aberrant methylation at
      genomically imprinted loci. Among others, members of the NLRP gene family are
      involved in the etiology of imprinting defects. Thus, a functional link between
      PE, NLRP gene mutations and aberrant imprinting can be assumed. Therefore we
      analyzed a cohort of 47 PE patients for NLRP gene mutations by next generation
      sequencing. In 25 fetuses where DNA was available we determined the methylation
      status at the imprinted locus. With the exception of one woman heterozygous for a
      missense variant in the NLRP7 gene (NM_001127255.1(NLRP7):c.542G>C) we could not
      identify further carriers, in the fetal DNA normal methylation patterns were
      observed. Thus, our negative screening results in a well-defined cohort indicate
      that NLRP mutations are not a relevant cause of PE, though strong evidence for a
      functional link between NLRP mutations, PE and aberrant methylation exist.

PMID- 28753544
TI  - Effect of female genital cutting performed by health care professionals on labor
      complications in Egyptian women: a prospective cohort study.
AB  - AIM: To examine the effect of the degree of female genital cutting (FGC)
      performed by health-care professionals on perineal scarring; delivery mode;
      duration of second stage of labor; incidence of perineal tears and episiotomy in
      a cohort of uncircumcised versus circumcised (types I and II) women. METHODS: A
      prospective cohort study included 450 primigravida women in active labor
      attending the Faculty of Medicine Cairo University Hospital between January 2013
      and August 2014. Women were divided into three groups based on medical
      examination upon admission. Group I (Control) included 150 uncut women, Group II
      included 150 women with type I FGC and Group III included 150 women with type II
      FGC. A structured questionnaire elicited the information on women's socio
      demographic characteristics including age, residence, occupation, educational
      level, age of marriage and FGC circumstances. Association between FGC and labor
      complications was examined. MAIN OUTCOMES: risk of perineal scarring; delivery
      mode; duration of second stage of labor; incidence of perineal tears and
      episiotomy. RESULTS: Family history of genitally cut mother/sister was the most
      significant socio-demographic factor associated with FGC. FGC especially type II
      was associated with significantly higher incidence of vulvar scar (P<0.0002),
      perineal tears (P<0.0001) and increased likelihood of additional vaginal and
      perineal trauma [odds ratio (OR): 1.85, 95% CI: 0.60-5.65. P<=0.001]. There was
      insignificant difference in risks of cesarean section (CS), instrumental
      delivery, episiotomy and short-term neonatal outcomes. CONCLUSION: The study
      strengthens the evidence that FGC increases the risk of tears in spite of
      medicalization of the practice.

PMID- 28753545
TI  - Adjuvant administration of 17-alpha-hydroxy-progesterone caproate in women with
      three or more second trimester pregnancy losses undergoing cervical cerclage is
      no more effective than cerclage alone.
AB  - OBJECTIVE: To investigate the role of adjuvant 17-alpha-hydroxy-progesterone
      caproate (17OHP-C) in reducing the risk of preterm delivery <34 weeks and adverse
      perinatal outcomes in women with >=3 second trimester pregnancy losses attributed
      to cervical insufficiency undergoing prophylactic cerclage. MATERIAL AND METHODS:
      Retrospective cohort study of women with prophylactic cerclage placed between
      2006 and 2014 divided into a cohort of (i) those receiving adjuvant 17OHP-C
      (n=43), and (ii) controls with cerclage alone (n=59). RESULTS: Demographic
      characteristics were comparable in both groups. There was no significant
      difference in gestational age at delivery between the cerclage-17OHP-C group
      (33.4+/-5.6 weeks) and the cerclage-alone group (34.4+/-4.6 weeks); P=0.33. We
      noted a non-significant increase for deliveries <34 weeks in the cerclage-17OHP-C
      group (44.2%) compared to controls (28.8%) which remained non-significant after
      adjusting for confounders; P=0.46. There was no statistically significant
      difference in the rate of delivery <37, 32, 28 and 24 weeks. Adverse neonatal
      outcomes were comparable in both groups (cerclage-17OHP-C 48.8% vs. cerclage
      alone 39%); P=0.43. CONCLUSION: Intramuscular 17OHP-C in combination with
      prophylactic cerclage in women with cervical insufficiency and >=3 second
      trimester pregnancy losses had no synergistic effect in reducing the rate of
      recurrent preterm birth or improving perinatal outcomes.

PMID- 28753546
TI  - Comparison of healthcare utilization and outcomes by gestational diabetes
      diagnostic criteria.
AB  - OBJECTIVE: To compare healthcare utilization and outcomes using the Carpenter
      Coustan (CC) criteria vs. the National Diabetes Data Group (NDDG) criteria for
      gestational diabetes mellitus (GDM). METHODS: This is a retrospective cohort
      study. Prior to 8/21/2013, patients were classified as "GDM by CC" if they met
      criteria. After 8/21/2013, patients were classified as "GDM by NDDG" if they met
      criteria and "Meeting CC non-GDM" if they met CC, but failed to reach NDDG
      criteria. "Non-GDM" women did not meet any criteria for GDM. Records were
      reviewed after delivery. RESULTS: There was a 41% reduction in GDM diagnosed
      using NDDG compared to CC (P=0.01). There was no significant difference in triage
      visits, ultrasounds for growth or hospital admissions. Women classified as
      "Meeting CC non-GDM" were more likely to have preeclampsia than "GDM by CC" women
      [OR 11.11 (2.7, 50.0), P=0.0006]. Newborns of mothers "Meeting CC non-GDM" were
      more likely to be admitted to neonatal intensive care units than "GDM by CC" [OR
      6.25 (1.7, 33.3), P=0.006], "GDM by NDDG" [OR 5.56 (1.3, 33.3), P=0.018] and "Non
      GDM" newborns [OR 6.47 (2.6, 14.8), P=0.0003]. CONCLUSION: Using the NDDG
      criteria may increase healthcare costs because while it decreases the number of
      patients being diagnosed with GDM, it may also increase maternal and neonatal
      complications without changing maternal healthcare utilization.

PMID- 28753547
TI  - Clarification of the methods and statistics in the study "Planned home birth and
      the association with neonatal hypoxic ischemic encephalopathy".

PMID- 28753548
TI  - Assessment of strain and dyssynchrony in normal fetuses using speckle tracking
      echocardiography - comparison of three different ultrasound probes.
AB  - OBJECTIVE: To evaluate segmental left (LV-S) and right (RV-S) ventricular strain
      as well as longitudinal mechanical myocardial dyssynchrony as a time difference
      between peaks in strain of both ventricles in fetuses (two-chamber-dyssynchrony,
      2C-DYS) using speckle tracking echocardiography (STE). The aim of our study was
      to evaluate the influence of data acquisition on the results of STE measurement
      using different ultrasound probes. METHODS: We prospectively recorded cardiac
      cycles of four-chamber views of 56 normal fetuses with three different ultrasound
      probes and analyzed them offline with speckle tracking imaging software.
      Furthermore, we looked at a possible influence of heartbeat variability (beat-to
      beat variability). RESULTS: The evaluation of the parameters was feasible with
      all three probes in 53 cases. There was no influence of heartbeat variability and
      no noticeable differences in 2C-DYS, LV-S and RV-S in all cases and for all three
      probes determined. CONCLUSION: Assessment of strain and dyssynchrony using STE
      with three different probes is comparable. Further research is needed to validate
      dyssynchrony as a predictor for fetal outcome.

PMID- 28753549
TI  - First trimester beta-hCG and estradiol levels in singleton and twin pregnancies
      after assisted reproduction.
AB  - Objective To compare levels of beta-hCG and estradiol collected during the first
      trimester in singleton and twin pregnancies following assisted reproduction
      technologies (ART). Methods We prospectively evaluated 50 singleton and 47
      dichorionic twin pregnancies that eventually ended in live births. Patients were
      recruited from a single ART center with standard treatment protocols followed by
      fresh embryo transfers. Hormone measurements were performed within a narrow
      gestational age range and analyzed in a single laboratory thus minimizing inter-
      and intra-assay variability. We measured serum beta-hCG at 13 days after embryo
      transfer as well as samples of beta-hCG and estradiol at 8-9 weeks+6 days.
      Results No significant differences existed between singletons and twins in
      respect to demographic and cycle characteristics. beta-hCG and estradiol were all
      significantly higher in twins (P<0.05). Conclusion The data confirms the higher
      levels of beta-hCG and estradiol in twins, pointing to the potential role of
      these placental hormones in early support of a twin pregnancy.

PMID- 28753550
TI  - Causes of death among full term stillbirths and early neonatal deaths in the
      Region of Southern Denmark.
AB  - OBJECTIVE: We examined the causes of death amongst full term stillbirths and
      early neonatal deaths. METHODS: Our cohort includes women in the Region of
      Southern Denmark, who gave birth at full term to a stillborn infant or a neonate
      who died within the first 7 days from 2010 through 2014. Demographic, biometric
      and clinical variables were analyzed to assess the causes of death using two
      classification systems: causes of death and associated conditions (CODAC) and a
      Danish system based on initial causes of fetal death (INCODE). RESULTS: A total
      of 95 maternal-infant cases were included. Using the CODAC and INCODE
      classification systems, we found that the causes of death were unknown in 59/95
      (62.1%). The second most common cause of death in CODAC was congenital anomalies
      in 10/95 (10.5%), similar to INCODE with fetal, genetic, structural and
      karyotypic anomalies in 11/95 (11.6%). The majority of the mothers were healthy,
      primiparous, non-smokers, aged 20-34 years and with a normal body mass index
      (BMI). CONCLUSION: Based on an unselected cohort from an entire region in
      Denmark, the cause of stillbirth and early neonatal deaths among full term
      infants remained unknown for the vast majority.

PMID- 28753551
TI  - Design, synthesis, and antibacterial activity of novel 8-methoxyquinoline-2
      carboxamide compounds containing 1,3,4-thiadiazole moiety.
AB  - A series of novel 8-methoxyquinoline-2-carboxamide compounds containing 1,3,4
      thiadiazole moiety was designed and synthesized by using an active substructure
      combination method. Then, the antibacterial activities of all the target
      compounds were evaluated in vitro against three Gram-positive bacteria and three
      Gram-negative bacteria. The antibacterial assay showed that some target compounds
      displayed moderate to good antibacterial efficacy in comparison with the
      reference drug Chloromycin. Some interesting results of structure-activity
      relationships were also discussed.

PMID- 28753552
TI  - Overexpression of c-Myc enhances recombinant protein production in High Five
      cells after baculovirus infection.
AB  - Due to their numerous advantages, baculovirus expression vector systems (BEVS)
      have been widely used to express recombinant proteins for different purposes.
      Different strategies have been adopted to increase recombinant protein
      production. In this study, we transiently or stably expressed mouse c-Myc in High
      Five cells using a commercial pIB/V5 vector. Under the control of the OpIE2
      promoter, this vector could enhance recombinant protein production. We found that
      transient expression of c-Myc in High Five cells improved recombinant protein
      production. Furthermore, we established two stable cell lines, High Five-c-Myc #1
      and High Five-c-Myc #2, that stably expressed mouse c-Myc. We further found that
      the expression level of the recombinant protein was increased in these stable
      cell lines compared to control cell lines. These data indicate that
      overexpressing c-Myc in cells is a promising way to improve recombinant protein
      production in BEVS.

PMID- 28753588
TI  - Chronic discrimination and bodily pain in a multiethnic cohort of midlife women
      in the Study of Women's Health Across the Nation.
AB  - A growing literature links discrimination to key markers of biobehavioral health.
      While racial or ethnic differences in pain are seen in experimental and clinical
      studies, the authors were interested in how chronic discrimination contributes to
      pain within multiple racial or ethnic groups over time. Participants were 3056
      African American, Caucasian, Chinese, Hispanic, and Japanese women from the Study
      of Women's Health Across the Nation. The Everyday Discrimination Scale was
      assessed from baseline through 13 follow-up examinations. The bodily pain
      subscale of the MOS 36-Item Short-Form Health Survey (SF-36) was assessed
      annually. There were large racial or ethnic differences in reports of
      discrimination and pain. Discrimination attributions also varied by race or
      ethnicity. In linear mixed model analyses, initially adjusted for age, education,
      and pain medications, chronic everyday discrimination was associated with more
      bodily pain in all ethnic groups (beta = -5.84; P < 0.002 for Japanese; beta = 
      6.17; P < 0.001 for African American; beta = -8.74; P < 0.001 for Chinese; beta =
      -10.54; P < 0.001 for Caucasians; beta = -12.82; P < 0.001 for Hispanic).
      Associations remained significant in all ethnic groups after adjusting for
      additional covariates in subsequent models until adding depressive symptoms as
      covariate; in the final fully-adjusted models, discrimination remained a
      significant predictor of pain for African American (beta = -4.50; P < 0.001),
      Chinese (beta = -6.62; P < 0.001), and Caucasian (beta = -7.86; P < 0.001) women.
      In this longitudinal study, experiences of everyday discrimination were strongly
      linked to reports of bodily pain for the majority of women. Further research is
      needed to determine if addressing psychosocial stressors, such as discrimination,
      with patients can enhance clinical management of pain symptoms.

PMID- 28753589
TI  - Differential Expression of Tubulin Acetylase and Deacetylase Between the Damaged
      Central and Peripheral Branch of Dorsal Root Ganglion Neurons.
AB  - BACKGROUND The differences between the peripheral and central branches of the
      dorsal root ganglion (DRG) have not been fully elucidated. This study aimed to
      explore the expression of tubulin post-translational modifications (acetylation
      and deacetylation) between damaged peripheral and central branches of DRG
      neurons. MATERIAL AND METHODS Fifty Sprague-Dawley rats were randomly assigned to
      five groups with 10 rats in each group. These five groups consisted of spinal
      nerve ligation (SNL) at 24 hour and 48 hour, and cauda equina compression (CEC)
      at 24 hour and 48 hour, and a sham group. SNL injury in rats was induced by
      ligating L5 and L6 spinal nerves with 1-0 silk thread outboard the DRGs. CEC
      injury in rats was induced by a piece of silicone (10*1*1 mm) placed under the
      laminae of the L5-6 vertebra. Sham-operated rats underwent a simple laminectomy
      in L4, but silicone was not implanted. The expression profile of acetylase and
      deacetylase was examined by real-time PCR, Western blotting, and
      immunohistochemistry. RESULTS In the experimental groups, rats presented
      increased expression of acetylase (NAT1 and MEC-17) and decreased expression of
      deacetylase (Sirt2 and HDAC6) levels. Additionally, the expression of NAT1 and
      MEC-17 was gradually increased in DRG neurons following peripheral axonal injury
      compared to central axonal injury in a time-dependent manner. Conversely, the
      expression of Sirt2 and HDAC6 was gradually decreased in DRG neurons following
      peripheral axonal injury compared to central axonal injury in a time-dependent
      manner. CONCLUSIONS Our study indicated that insufficiency of acetylase and
      upregulation of deacetylase in DRG neurons after central axonal injury may
      contribute to the pathogenesis of cauda equine syndrome.

PMID- 28753590
TI  - Ectopic abdominal pregnancy due to uterine perforation after an attempt to
      terminate pregnancy: a case presentation.
AB  - Secondary abdominal ectopic pregnancy is rare in clinical practice, but may lead
      to an increased maternal mortality. We present the case of a patient with an
      abdominal pregnancy secondary to a uterine perforation caused by a voluntary
      attempt to interrupt pregnancy that presented with nine weeks of abdominal pain
      and minimal vaginal bleeding which was mistakenly diagnosed as acute pelvic
      inflammatory disease, urinary tract infection, and post-abortion products of
      conception. Finally, the abdominal ultrasound test found an abdominal ectopic
      pregnancy. An exploratory laparotomy was performed and the fetus and placenta
      were removed without difficulties with a favorable postoperative course. It was
      concluded that uterine perforation during curettage of the cavity went unnoticed,
      leading to secondary abdominal implantation of pregnancy with a inconclusive
      clinical presentation, where ultrasound plays a fundamental diagnostic role.
      Laparotomy is indicated in most of these cases.

PMID- 28753591
TI  - Mucinous carcinoma of the breast: a case report and review of the literature.
AB  - Mucinous carcinoma of the breast is a rare histological type, which represents
      between 1 and 4% of breast cancers. Treatment does not differ from other
      histological types, and it occurs more frequently in older adult women. Prognosis
      is good. We report the case of a 72-year-old patient with a 1-year disease course
      characterized by the appearance of a slow-growing tumor in the left upper
      quadrant of the left breast, in which the core biopsy showed mucinous breast
      carcinoma of a low nuclear grade. The patient underwent quadrantectomy plus a
      sentinel node biopsy, which confirmed the initial diagnosis.

PMID- 28753592
TI  - Evidence and information in medicine.

PMID- 28753593
TI  - Health and society: towards a human-centered medicine.

PMID- 28753594
TI  - The first-in-class alkylating HDAC inhibitor EDO-S101 is highly synergistic with
      proteasome inhibition against multiple myeloma through activation of multiple
      pathways.

PMID- 28753595
TI  - Clinico-biological significance of suppressor of cytokine signaling 1 expression
      in acute myeloid leukemia.
AB  - Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of
      signal transducers and activators of transcription-induced inhibitors, takes part
      in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor
      carcinogenesis is complex and there have been no studies concerning the clinic
      biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here,
      we first identified that higher bone marrow (BM) SOCS1 expression was closely
      associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively
      correlated with CEBPA mutation in patients with de novo AML. Compared to patients
      with lower SOCS1 expression, those with higher expression had lower complete
      remission rates and shorter overall survival. Further, higher expression of SOCS1
      in the BM was an independent unfavorable prognostic factor irrespective of age,
      white blood cell, cytogenetics and gene mutations. Next, we generated zebrafish
      model overexpressing SOCS1 by spi1 promoter, which showed kidney marrow from
      adult SOCS1 zebrafish had increased myelopoiesis, myeloid progenitors and the
      kidney or spleen structure were effaced and distorted, mimicking leukemia
      phenotype. The SOCS1/FLT3-ITD double transgenic fish could further facilitate the
      leukemic process. The results indicate SOCS1 plays an important role in AML and
      its higher expression serves as a new biomarker to risk-stratify AML patients.

PMID- 28753596
TI  - Inhibition of IkappaBbeta/NFkappaB signaling prevents LPS-induced IL1beta
      expression without increasing apoptosis in the developing mouse lung.
AB  - BackgroundThe pro-inflammatory consequences of IL1beta expression contribute to
      the pathogenesis of bronchopulmonary dysplasia. Selectively targeting
      Lipopolysaccharide (LPS)-induced IkappaBbeta/NFkappaB signaling attenuates
      IL1beta mRNA expression in macrophages. Whether targeting IkappaBbeta/NFkappaB
      signaling affects the anti-apoptotic gene expression, a known consequence of
      global LPS-induced NFkappaB inhibition, is unknown.MethodsMacrophages (RAW 264.7,
      bone marrow-derived macrophage) were assessed for LPS-induced IL1beta
      mRNA/protein expression, anti-apoptotic gene expression, cell viability (trypan
      blue exclusion), and activation of apoptosis (caspase-3 and PARP cleavage)
      following pharmacologic and genetic attenuation of IkappaBbeta/NFkappaB
      signaling. Expressions of IL1beta and anti-apoptotic genes were assessed in
      endotoxemic newborn mice (P0) with intact (WT), absent (IkappaBbeta KO), and
      attenuated (IkappaBbeta overexpressing) IkappaBbeta/NFkappaB signaling.ResultsIn
      cultured macrophages, pharmacologic and genetic inhibition of LPS-induced
      IkappaBbeta/NFkappaB signaling significantly attenuated IL1beta mRNA and protein
      expression. Importantly, targeting IkappaBbeta/NFkappaB signaling did not
      attenuate LPS-induced expression of anti-apoptotic genes or result in cell death.
      In endotoxemic neonatal mice, targeting LPS-induced IkappaBbeta/NFkappaB
      signaling significantly attenuated pulmonary IL1beta expression without affecting
      the anti-apoptotic gene expression.ConclusionTargeting IkappaBbeta/NFkappaB
      signaling prevents LPS-induced IL1beta expression without inducing apoptosis in
      cultured macrophages and in the lungs of endotoxemic newborn mice. Inhibiting
      this pathway may prevent inflammatory injury without affecting the protective
      role of NFkappaB activity in the developing lung.

PMID- 28753597
TI  - Urotensin 2 in Kawasaki disease pathogenesis.
AB  - BackgroundGenetic variation in calcium signaling pathways is associated with
      Kawasaki disease (KD) susceptibility and coronary artery aneurysms (CAA).
      Expression quantitative trait locus analysis for KD-associated variants in
      calcium/sodium channel gene solute carrier family 8 member 1 (SLC8A1) revealed an
      effect on expression of urotensin 2 (UTS2). We speculated that UTS2 is influenced
      by genetic variation in SLC8A1 and contributes to disease pathogenesis.MethodsWe
      measured levels of UTS2 and its receptor in blood and tissues using quantitative
      reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent
      assay, and immunohistochemical staining.ResultsUTS2 transcript levels were higher
      in the whole blood of subjects with KD homozygous for three risk alleles in
      SLC8A1 (P=0.002-0.006). Increased levels of plasma UTS2 varied as a function of
      SLC8A1 genotype (P=0.008-0.04). UTS2 and UTS2 receptor were expressed in
      mononuclear inflammatory cells and spindle-shaped cells in the coronary arterial
      wall of a patient suffering from KD with CAA and in a femoral endarterectomy
      specimen from an adult patient with peripheral aneurysms following KD in
      childhood.ConclusionHost genetics influences UTS2 levels, which may contribute to
      inflammation and cardiovascular damage in KD.

PMID- 28753598
TI  - Genetics: new tales from ancient DNA.

PMID- 28753599
TI  - Probes &Drugs portal: an interactive, open data resource for chemical biology.

PMID- 28753600
TI  - sCMOS noise-correction algorithm for microscopy images.

PMID- 28753601
TI  - A hierarchical Bayesian model for understanding the spatiotemporal dynamics of
      the intestinal epithelium.
AB  - Our work addresses two key challenges, one biological and one methodological.
      First, we aim to understand how proliferation and cell migration rates in the
      intestinal epithelium are related under healthy, damaged (Ara-C treated) and
      recovering conditions, and how these relations can be used to identify mechanisms
      of repair and regeneration. We analyse new data, presented in more detail in a
      companion paper, in which BrdU/IdU cell-labelling experiments were performed
      under these respective conditions. Second, in considering how to more rigorously
      process these data and interpret them using mathematical models, we use a
      probabilistic, hierarchical approach. This provides a best-practice approach for
      systematically modelling and understanding the uncertainties that can otherwise
      undermine the generation of reliable conclusions-uncertainties in experimental
      measurement and treatment, difficult-to-compare mathematical models of underlying
      mechanisms, and unknown or unobserved parameters. Both spatially discrete and
      continuous mechanistic models are considered and related via hierarchical
      conditional probability assumptions. We perform model checks on both in-sample
      and out-of-sample datasets and use them to show how to test possible model
      improvements and assess the robustness of our conclusions. We conclude, for the
      present set of experiments, that a primarily proliferation-driven model suffices
      to predict labelled cell dynamics over most time-scales.

PMID- 28753602
TI  - Automated incorporation of pairwise dependency in transcription factor binding
      site prediction using dinucleotide weight tensors.
AB  - Gene regulatory networks are ultimately encoded by the sequence-specific binding
      of (TFs) to short DNA segments. Although it is customary to represent the binding
      specificity of a TF by a position-specific weight matrix (PSWM), which assumes
      each position within a site contributes independently to the overall binding
      affinity, evidence has been accumulating that there can be significant
      dependencies between positions. Unfortunately, methodological challenges have so
      far hindered the development of a practical and generally-accepted extension of
      the PSWM model. On the one hand, simple models that only consider dependencies
      between nearest-neighbor positions are easy to use in practice, but fail to
      account for the distal dependencies that are observed in the data. On the other
      hand, models that allow for arbitrary dependencies are prone to overfitting,
      requiring regularization schemes that are difficult to use in practice for non
      experts. Here we present a new regulatory motif model, called dinucleotide weight
      tensor (DWT), that incorporates arbitrary pairwise dependencies between positions
      in binding sites, rigorously from first principles, and free from tunable
      parameters. We demonstrate the power of the method on a large set of ChIP-seq
      data-sets, showing that DWTs outperform both PSWMs and motif models that only
      incorporate nearest-neighbor dependencies. We also demonstrate that DWTs
      outperform two previously proposed methods. Finally, we show that DWTs inferred
      from ChIP-seq data also outperform PSWMs on HT-SELEX data for the same TF,
      suggesting that DWTs capture inherent biophysical properties of the interactions
      between the DNA binding domains of TFs and their binding sites. We make a suite
      of DWT tools available at dwt.unibas.ch, that allow users to automatically
      perform 'motif finding', i.e. the inference of DWT motifs from a set of
      sequences, binding site prediction with DWTs, and visualization of DWT 'dilogo'
      motifs.

PMID- 28753603
TI  - A Comparison between heat transfer performance of rectangular and semicircular
      tubes considering boundary effects on Brownian motions in the presence of Ag /
      water nanofluids: Applicable in the design of cooling system of photovoltaic
      cells.
AB  - The present study aims to experimentally investigate heat transfer performance of
      rectangular and semicircular tubes in the presence of Ag / water nanofluids. The
      nanoparticles of Ag (silver) were used in seven different volume concentrations
      of 0.03%, 0.07%, 0.1%, 0.2%, 0.4%, 1% and 2%. The experiment was conducted in
      relatively low Reynolds numbers of 301 to 740. A heater with the power of 200 W
      was used to keep the outer surface of the tubes under a constant heat flux
      condition. In addition, the rectangular tube has been designed within the same
      length as the semicircular one and also within the same hydraulic diameter.
      Moreover, the average nanoparticles size was 20 nm. The outcome results of the
      present empirical work indicate that, for all the examined Reynolds numbers, the
      semicircular tube has higher convective heat transfer coefficient for all the
      utilized volume concentrations of Ag nanoparticles. The possible reasons behind
      this advantage are discussed through the present work mainly by taking the
      boundary effect on Brownian motions into account. Coming to this point that the
      conventional design for cooling system of photovoltaic cells is a heat sink with
      the rectangular graves, it is discussed that using a semicircular design may have
      the advantage over the rectangular one in convective heat transfer coefficient
      enhancement and hence a better cooling performance for these solar cells.

PMID- 28753604
TI  - SOCS1 function in BCR-ABL mediated myeloproliferative disease is dependent on the
      cytokine environment.
AB  - Treatment with tyrosine kinase inhibitors is the standard of care for
      Philadelphia chromosome positive leukemias. However the eradication of leukemia
      initiating cells remains a challenge. Circumstantial evidence suggests that the
      cytokine microenvironment may play a role in BCR-ABL mediated leukemogenesis and
      in imatinib resistance. Gene expression analyses of BCR-ABL positive ALL long
      term cultured cells revealed strong reduction of SOCS mRNA expression after
      imatinib treatment, thereby demonstrating a strong inhibition of cytokine
      signaling. In this study we employed SOCS1-a strong inhibitor of cytokine
      signaling-as a tool to terminate external cytokine signals in BCR-ABL transformed
      cells in vitro and in vivo. In colony formation assays with primary bone marrow
      cells, expression of SOCS1 decreased colony numbers under pro-proliferative
      cytokines, while it conferred growth resistance to anti-proliferative cytokines.
      Importantly, co-expression of SOCS1 with BCR-ABL led to the development of a MPD
      phenotype with a prolonged disease latency compared to BCR-ABL alone in a murine
      bone marrow transplantation model. Interestingly, SOCS1 co-expression protected
      20% of mice from MPD development. In summary, we conclude that under pro
      proliferative cytokine stimulation at the onset of myeloproliferative diseases
      SOCS1 acts as a tumor suppressor, while under anti-proliferative conditions it
      exerts oncogenic function. Therefore SOCS1 can promote opposing functions
      depending on the cytokine environment.

PMID- 28753605
TI  - Spatiotemporal analysis of projected impacts of climate change on the major C3
      and C4 crop yield under representative concentration pathway 4.5: Insight from
      the coasts of Tamil Nadu, South India.
AB  - India's dependence on a climate sensitive sector like agriculture makes it highly
      vulnerable to its impacts. However, agriculture is highly heterogeneous across
      the country owing to regional disparities in exposure, sensitivity, and adaptive
      capacity. It is essential to know and quantify the possible impacts of changes in
      climate on crop yield for successful agricultural management and planning at a
      local scale. The Hadley Centre Global Environment Model version 2-Earth System
      (HadGEM-ES) was employed to generate regional climate projections for the study
      area using the Regional Climate Model (RCM) RegCM4.4. The dynamics in potential
      impacts at the sub-district level were evaluated using the Representative
      Concentration Pathway 4.5 (RCPs). The aim of this study was to simulate the crop
      yield under a plausible change in climate for the coastal areas of South India
      through the end of this century. The crop simulation model, the Decision Support
      System for Agrotechnology Transfer (DSSAT) 4.5, was used to understand the
      plausible impacts on the major crop yields of rice, groundnuts, and sugarcane
      under the RCP 4.5 trajectory. The findings reveal that under the RCP 4.5 scenario
      there will be decreases in the major C3 and C4 crop yields in the study area.
      This would affect not only the local food security, but the livelihood security
      as well. This necessitates timely planning to achieve sustainable crop
      productivity and livelihood security. On the other hand, this situation warrants
      appropriate adaptations and policy intervention at the sub-district level for
      achieving sustainable crop productivity in the future.

PMID- 28753606
TI  - The RhoJ-BAD signaling network: An Achilles' heel for BRAF mutant melanomas.
AB  - Genes and pathways that allow cells to cope with oncogene-induced stress
      represent selective cancer therapeutic targets that remain largely undiscovered.
      In this study, we identify a RhoJ signaling pathway that is a selective
      therapeutic target for BRAF mutant cells. RhoJ deletion in BRAF mutant
      melanocytes modulates the expression of the pro-apoptotic protein BAD as well as
      genes involved in cellular metabolism, impairing nevus formation, cellular
      transformation, and metastasis. Short-term treatment of nascent melanoma tumors
      with PAK inhibitors that block RhoJ signaling halts the growth of BRAF mutant
      melanoma tumors in vivo and induces apoptosis in melanoma cells in vitro via a
      BAD-dependent mechanism. As up to 50% of BRAF mutant human melanomas express high
      levels of RhoJ, these studies nominate the RhoJ-BAD signaling network as a
      therapeutic vulnerability for fledgling BRAF mutant human tumors.

PMID- 28753607
TI  - Total and differential WBC counts are related with coronary artery
      atherosclerosis and increase the risk for cardiovascular disease in Koreans.
AB  - OBJECTIVE: Inflammation is a key mechanism of atherosclerosis. White blood cells
      (WBCs) play a pivotal role in the inflammatory process. We investigated the
      relationships between total and differential WBC counts and multi-detector
      cardiac computed tomography (MDCT) findings, as well as the risk of
      cardiovascular disease in asymptomatic patients in Korea. MATERIALS AND METHODS:
      We recruited asymptomatic men (n = 7274) and women (n = 5478) aged >=30 years who
      were free of known coronary heart disease. All patients underwent MDCT during a
      routine health check-up in the Seoul National University Bundang Hospital between
      2006 and 2007, and were followed-up for 5.6 years. We reviewed medical records
      for cardiovascular diseases (CVDs) and covariates. RESULTS: In covariate-adjusted
      logistic regression models for MDCT findings, subjects within the third tertile
      of all WBC subtypes had a higher risk for significant stenosis and noncalcified
      plaques compared with the first tertile of each subtype. In Cox proportional
      hazard regression models for the risk of CVDs, subjects within the third tertiles
      of lymphocytes and monocytes were at an increased risk of CVDs (total WBC, HR =
      1.22 [1.02-1.44]; lymphocyte, HR = 1.47 [1.25-1.74]; monocytes, HR = 1.26 [1.02
      1.35]) even after further adjustment for covariates and coronary artery stenosis.
      CONCLUSIONS: Total WBC counts were related with the severity of coronary artery
      disease, and higher WBC counts increased the risk of CVDs in asymptomatic Koreans
      mainly by virtue of monocytes.

PMID- 28753608
TI  - Extensive sonographic ulnar nerve enlargement above the medial epicondyle is a
      characteristic sign in Hansen's neuropathy.
AB  - OBJECTIVE: Earlier studies have shown sonographic enlargement of the ulnar nerve
      in patients with Hansen's neuropathy. The present study was performed to
      determine whether sonography or electrophysiological studies can detect the
      specific site of ulnar nerve pathology in leprosy. METHODS: Eighteen patients
      (thirty arms) with Hansen's disease and an ulnar neuropathy of whom 66% had
      borderline tuberculoid (BT), 27% lepromatous leprosy (LL) and 7% mid-borderline
      (BB) leprosy were included in the study. Cross-sectional area (CSA) of ulnar
      nerve was measured every two centimeters from wrist to medial epicondyle and from
      there to axilla. All patients underwent standard motor and sensory nerve
      conduction studies of the ulnar nerve. Thirty age and sex matched controls
      underwent similar ulnar nerve CSA measurements and conduction studies. RESULTS:
      Ulnar nerve was clinically palpable in 19 of the 30 arms of patients. Motor and
      sensory nerve conduction studies of the ulnar nerve showed a reduced compound
      motor action potential and sensory nerve action potential amplitude in all
      patients. Motor Conduction Velocity (MCV) in patients were slower in comparison
      to controls, especially at the elbow and upper arm, but unable to exactly locate
      the site of the lesion. In comparison to controls the ulnar nerveCSA was larger
      in the whole arm in patients and quite specific the maximum enlargement was seen
      between nulnar sulcus and axilla, peaking at four centimeters above the sulcus.
      CONCLUSIONS: A unique sonographic pattern of nerve enlargement is noted in
      patients with ulnar neuropathy due to Hansen's disease, while this was not the
      case for the technique used until now, the electrodiagnostic testing. The
      enlargement starts at ulnar sulcus and is maximum four centimeters above the
      medial epicondyle and starts reducing further along the tract. This
      characteristic finding can help especially in diagnosing pure neuritic type of
      Hansen's disease, in which skin lesions are absent, and alsoto differentiate
      leprosy from other neuropathies in which nerve enlargement can occur.

PMID- 28753609
TI  - Correction: Use of Oral Cholera Vaccine and Knowledge, Attitudes, and Practices
      Regarding Safe Water, Sanitation and Hygiene in a Long-Standing Refugee Camp,
      Thailand, 2012-2014.
AB  - [This corrects the article DOI: 10.1371/journal.pntd.0005210.].

PMID- 28753610
TI  - Correction: Diagnosis of Bacterial Bloodstream Infections: A 16S Metagenomics
      Approach.
AB  - [This corrects the article DOI: 10.1371/journal.pntd.0004470.].

PMID- 28753611
TI  - The impact of the quality of care and other factors on progression of chronic
      kidney disease in Thai patients with Type 2 Diabetes Mellitus: A nationwide
      cohort study.
AB  - OBJECTIVE: The present study investigates the impact of quality of care (QoC) and
      other factors on chronic kidney disease (CKD) stage progression among Type 2
      Diabetes Mellitus (T2DM) patients. METHODS: This study employed a retrospective
      cohort from a nationwide Diabetes and Hypertension study involving 595 Thai
      hospitals. T2DM patients who were observed at least 2 times in the 3 years follow
      up (between 2011-2013) were included in our study. Ordinal logistic mixed effect
      regression modeling was used to investigate the association between the QoC and
      other factors with CKD stage progression. RESULTS: After adjusting for
      covariates, we found that the achievement of the HbA1c clinical targets (<=7%)
      was the only QoC indicator protective against the CKD stage progression (adjusted
      OR = 0.76; 95%CI = 0.59-0.98; p<0.05). In terms of other covariates, age,
      occupation, type of health insurance, region of residence, HDL-C, triglyceride,
      hypertension and insulin sensitizer were also strongly associated with CKD stage
      progression. CONCLUSIONS: This cohort study demonstrates the achievement of the
      HbA1c clinical target (<=7%) is the only QoC indicator protective against
      progression of CKD stage. Neither of the other clinical targets (BP and LDL-C)
      nor any process of care targets could be shown to be associated with CKD stage
      progression. Therefore, close monitoring of blood sugar control is important to
      slow CKD progression, but long-term prospective cohorts are needed to gain better
      insights into the impact of QoC indicators on CKD progression.

PMID- 28753612
TI  - Four alpha ganglion cell types in mouse retina: Function, structure, and
      molecular signatures.
AB  - The retina communicates with the brain using >=30 parallel channels, each carried
      by axons of distinct types of retinal ganglion cells. In every mammalian retina
      one finds so-called "alpha" ganglion cells (alphaRGCs), identified by their large
      cell bodies, stout axons, wide and mono-stratified dendritic fields, and high
      levels of neurofilament protein. In the mouse, three alphaRGC types have been
      described based on responses to light steps: On-sustained, Off-sustained, and Off
      transient. Here we employed a transgenic mouse line that labels alphaRGCs in the
      live retina, allowing systematic targeted recordings. We characterize the three
      known types and identify a fourth, with On-transient responses. All four alphaRGC
      types share basic aspects of visual signaling, including a large receptive field
      center, a weak antagonistic surround, and absence of any direction selectivity.
      They also share a distinctive waveform of the action potential, faster than that
      of other RGC types. Morphologically, they differ in the level of dendritic
      stratification within the IPL, which accounts for their response properties.
      Molecularly, each type has a distinct signature. A comparison across mammals
      suggests a common theme, in which four large-bodied ganglion cell types split the
      visual signal into four channels arranged symmetrically with respect to polarity
      and kinetics.

PMID- 28753613
TI  - Adaptive Swarm Balancing Algorithms for rare-event prediction in imbalanced
      healthcare data.
AB  - Clinical data analysis and forecasting have made substantial contributions to
      disease control, prevention and detection. However, such data usually suffer from
      highly imbalanced samples in class distributions. In this paper, we aim to
      formulate effective methods to rebalance binary imbalanced dataset, where the
      positive samples take up only the minority. We investigate two different meta
      heuristic algorithms, particle swarm optimization and bat algorithm, and apply
      them to empower the effects of synthetic minority over-sampling technique (SMOTE)
      for pre-processing the datasets. One approach is to process the full dataset as a
      whole. The other is to split up the dataset and adaptively process it one segment
      at a time. The experimental results reported in this paper reveal that the
      performance improvements obtained by the former methods are not scalable to
      larger data scales. The latter methods, which we call Adaptive Swarm Balancing
      Algorithms, lead to significant efficiency and effectiveness improvements on
      large datasets while the first method is invalid. We also find it more consistent
      with the practice of the typical large imbalanced medical datasets. We further
      use the meta-heuristic algorithms to optimize two key parameters of SMOTE. The
      proposed methods lead to more credible performances of the classifier, and
      shortening the run time compared to brute-force method.

PMID- 28753615
TI  - Clustering infection of hepatitis B virus genotype B4 among residents in Vietnam,
      and its genomic characters both intra- and extra-family.
AB  - Vietnam has a high rate of hepatitis B virus (HBV) infection and a high mortality
      rate from hepatocellular carcinoma. We performed a detailed genetic analysis of
      48 residents and four families from Binh Thuan Province, a southern coastal area
      of Vietnam. The route of infection and genomic characteristics related to
      hepatocellular carcinoma (HCC) were studied in HBV spread among carriers that we
      detected in our previous hepatitis survey. The HBV genotype was B4 in 91.7% and
      C1 in 8.3% of the cases. The intra-family's HBV sequence homology was high at
      96.8-99.4%. However, it was also high at 99.4-99.8% among residents of the same
      age and sex as family members. In addition, full genome analysis was performed in
      21 cases. The core region of all 20 isolates with genotype B4 was a recombinant
      of genotype C, and pre-S deletion was found in 20% of cases. The promoter
      mutation G1613A was found in 13.6% of cases, and a 24 bp insertion from nt1673 in
      the X region was found in 6.3% of cases. The phylogenetic tree and homology
      analysis of the HBV full genome suggested the probability and its possibility of
      horizontal transmission not only within families nor vertical transmission but
      within cohorts of the same generation in the population. Moreover, the HBV
      genotype B4 isolates were found not only to be recombinants of genotype C, which
      results in a high cancer risk, but also to have other risk of HCC, pre-S
      deletions, the G1613A mutation, and X region insertions corresponding to the
      promoter. These genomic characters were suggested to be one of the factors to
      explain the high HCC mortality rate in Vietnam.

PMID- 28753614
TI  - The Drosophila Duox maturation factor is a key component of a positive feedback
      loop that sustains regeneration signaling.
AB  - Regenerating tissue must initiate the signaling that drives regenerative growth,
      and sustain that signaling long enough for regeneration to complete. How these
      key signals are sustained is unclear. To gain a comprehensive view of the changes
      in gene expression that occur during regeneration, we performed whole-genome
      mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal
      discs. We used genetic tools to ablate the wing primordium to induce
      regeneration, and carried out transcriptional profiling of the regeneration
      blastema by fluorescently labeling and sorting the blastema cells, thus
      identifying differentially expressed genes. Importantly, by using genetic mutants
      of several of these differentially expressed genes we have confirmed that they
      have roles in regeneration. Using this approach, we show that high expression of
      the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is
      required during regeneration to produce reactive oxygen species (ROS), which in
      turn sustain JNK signaling during regeneration. We also show that JNK signaling
      upregulates mol expression, thereby activating a positive feedback signal that
      ensures the prolonged JNK activation required for regenerative growth. Thus, by
      whole-genome transcriptional profiling of regenerating tissue we have identified
      a positive feedback loop that regulates the extent of regenerative growth.

PMID- 28753616
TI  - Regeneration of the digestive system in the crinoid Himerometra robustipinna
      occurs by transdifferentiation of neurosecretory-like cells.
AB  - The structure and regeneration of the digestive system in the crinoid Himerometra
      robustipinna (Carpenter, 1881) were studied. The gut comprises a spiral tube
      forming radial lateral processes, which gives it a five-lobed shape. The
      digestive tube consists of three segments: esophagus, intestine, and rectum. The
      epithelia of these segments have different cell compositions. Regeneration of the
      gut after autotomy of the visceral mass progresses very rapidly. Within 6 h after
      autotomy, an aggregation consisting of amoebocytes, coelomic epithelial cells and
      juxtaligamental cells (neurosecretory neurons) forms on the inner surface of the
      skeletal calyx. At 12 h post-autotomy, transdifferentiation of the
      juxtaligamental cells starts. At 24 h post-autotomy these cells undergo a
      mesenchymal-epithelial-like transition, resulting in the formation of the luminal
      epithelium of the gut. Specialization of the intestinal epithelial cells begins
      on day 2 post-autotomy. At this stage animals acquire the mouth and anal opening.
      On day 4 post-autotomy the height of both the enterocytes and the visceral mass
      gradually increases. Proliferation does not play any noticeable role in gut
      regeneration. The immersion of animals in a 10-7 M solution of colchicine neither
      stopped formation of the lost structures nor caused accumulation of mitoses in
      tissues. Weakly EdU-labeled nuclei were observed in the gut only on day 2 post
      autotomy and were not detected at later regeneration stages. Single mitotically
      dividing cells were recorded during the same period. It is concluded that
      juxtaligamental cells play a major role in gut regeneration in H. robustipinna.
      The main mechanisms of morphogenesis are cell migration and transdifferentiation.

PMID- 28753617
TI  - Healthy lifestyle behaviours are positively and independently associated with
      academic achievement: An analysis of self-reported data from a nationally
      representative sample of Canadian early adolescents.
AB  - INTRODUCTION: The lifestyle behaviours of early adolescents, including diet,
      physical activity, sleep, and screen usage, are well established contributors to
      health. These behaviours have also been shown to be associated with academic
      achievement. Poor academic achievement can additionally contribute to poorer
      health over the lifespan. This study aims to characterize the associations
      between health behaviours and self-reported academic achievement. METHODS: Data
      from the 2014 Canadian Health Behaviour in School-Aged Children Study (n =
      28,608, ages 11-15) were analyzed. Students provided self-report of academic
      achievement, diet, physical activity, sleep duration, recreational screen time
      usage, height, weight, and socioeconomic status. Multi-level logistic regression
      was used to assess the relationship of lifestyle behaviours and body weight
      status with academic achievement while considering sex, age, and socioeconomic
      status as potential confounders. RESULTS: All health behaviours exhibited
      independent associations with academic achievement. Frequent consumption of
      vegetables and fruits, breakfast and dinner with family and regular physical
      activity were positively associated with higher levels of academic achievement,
      while frequent consumption of junk food, not meeting sleep recommendations, and
      overweight and obesity were negatively associated with high academic achievement.
      CONCLUSIONS: The present findings demonstrate that lifestyle behaviours are
      associated with academic achievement, potentially identifying these lifestyle
      behaviours as effective targets to improve academic achievement in early
      adolescents. These findings also justify investments in school-based health
      promotion initiatives.

PMID- 28753618
TI  - Clinical outcomes and mortality before and after implementation of a pediatric
      sepsis protocol in a limited resource setting: A retrospective cohort study in
      Bangladesh.
AB  - BACKGROUND: Pediatric sepsis has a high mortality rate in limited resource
      settings. Sepsis protocols have been shown to be a cost-effective strategy to
      improve morbidity and mortality in a variety of populations and settings. At
      Dhaka Hospital in Bangladesh, mortality from pediatric sepsis in high-risk
      children previously approached 60%, which prompted the implementation of an
      evidenced-based protocol in 2010. The clinical effectiveness of this protocol had
      not been measured. We hypothesized that implementation of a pediatric sepsis
      protocol improved clinical outcomes, including reducing mortality and length of
      hospital stay. MATERIALS AND METHODS: This was a retrospective cohort study of
      children 1-59 months old with a diagnosis of sepsis, severe sepsis or septic
      shock admitted to Dhaka Hospital from 10/25/2009-10/25/2011. The primary outcome
      was inpatient mortality pre- and post-protocol implementation. Secondary outcomes
      included fluid overload, heart failure, respiratory insufficiency, length of
      hospital stay, and protocol compliance, as measured by antibiotic and fluid bolus
      administration within 60 minutes of hospital presentation. RESULTS: 404 patients
      were identified by a key-word search of the electronic medical record; 328
      patients with a primary diagnosis of sepsis, severe sepsis, or septic shock were
      included (143 pre- and185 post-protocol) in the analysis. Pre- and post-protocol
      mortality were similar and not statistically significant (32.17% vs. 34.59%, p =
      0.72). The adjusted odds ratio (AOR) for post-protocol mortality was 1.55 (95%
      CI, 0.88-2.71). The odds for developing fluid overload were significantly higher
      post-protocol (AOR 3.45, 95% CI, 2.04-5.85), as were the odds of developing heart
      failure (AOR 4.52, 95% CI, 1.43-14.29) and having a longer median length of stay
      (AOR 1.81, 95% CI 1.10-2.96). There was no statistically significant difference
      in respiratory insufficiency (pre- 65.7% vs. post- 70.3%, p = 0.4) or antibiotic
      administration between the cohorts (pre- 16.08% vs. post- 12.43%, p = 0.42).
      CONCLUSIONS: Implementation of a pediatric sepsis protocol did not improve all
      cause mortality or length of stay and may have been associated with increased
      fluid overload and heart failure during the study period in a large, non
      governmental hospital in Bangladesh. Similar rates of early antibiotic
      administration may indicate poor protocol compliance. Though evidenced-based
      protocols are a potential cost-effective strategy to improve outcomes, future
      studies should focus on optimal implementation of context-relevant sepsis
      protocols in limited resource settings.

PMID- 28753619
TI  - Impact of organizational and individual factors on patient-provider
      relationships: A national survey of doctors, nurses and patients in China.
AB  - OBJECTIVES: To provide an empirical examination of patient-provider relationships
      (PPR) and its association with organizational and individual factors. METHODS: A
      national cross-sectional survey was conducted by stratified cluster sampling in
      77 hospitals across seven provinces in China between July 2014 and April 2015,
      involving 3621 doctors, 5561 nurses, and 8022 patients with response rates of
      62.93%, 61.16%, and 33.08%, respectively. Self-perceived PPR was the outcome
      variable. Organizational factors included hospital type (western medicine [WM]
      and traditional Chinese medicine [TCM] hospital); hospital level (tertiary and
      secondary hospital); area of specialization (internal medicine and surgery);
      ratio of doctors (nurses) to ward beds; doctors/nurses' concerns about
      performance assessment; and patients' perceptions of healthcare cost. Individual
      factors included consultation, listening to patients and socio-demographic
      factors. RESULTS: 54.6% of doctors, 36.6% of nurses, and 10.2% of patients
      perceived PPR as poor. Organizational factors independently associated with
      providers' perception of poor PPR included hospital type (WM vs TCM: OR = 1.25
      [95% CI: 1.06-1.47]) and concerns about performance assessment (high vs low
      levels: OR = 1.40 [95% CI: 1.14-1.72]) for doctors, and concerns about
      performance assessment (average vs low levels: OR = 0.79 [95% CI: 0.67-0.93]) for
      nurses. Those associated with patients' perception of poor PPR included hospital
      type (WM vs TCM: OR = 0.63 [95% CI: 0.53-0.74]) and hospital level (tertiary vs
      secondary: OR = 0.65 [95% CI: 0.51-0.82]). Doctors and nurses reporting listening
      to patients "frequently" had better perceptions of PPR (OR = 0.46 [95%CI: 0.38
      0.56] and 0.49 [95% CI: 0.41-0.59] for doctors and nurses, respectively), as did
      their patients (OR = 0.24 [95% CI: 0.18-0.31] and 0.54 [95% CI: 0.35-0.84] for
      doctors and nurses, respectively). CONCLUSIONS: Although our findings require
      validation in different organizational settings given the likely variability of
      these associations across systems, our results suggest that implementing moderate
      levels promoting the level of medical treatment, and broadening doctors/nurses
      training regarding listening to patients, may benefit to enhance PPR.

PMID- 28753620
TI  - Treatment combining aliskiren with paricalcitol is effective against progressive
      renal tubulointerstitial fibrosis via dual blockade of intrarenal renin.
AB  - The aim of this study was to assess any potential additive effects of a treatment
      combining aliskiren with paricalcitol on reducing renal fibrosis. C57BL/6J mice
      were treated individually with aliskiren and/or paricalcitol until 7 days after
      initiation of unilateral ureteral obstruction (UUO).In obstructed kidneys of UUO
      mice, monotherapy with aliskiren or paricalcitol significantly attenuated
      interstitial fibrosis, collagen IV accumulation, and alpha-smooth muscle actin-
      and terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling
      positive cells. The combination treatment showed additive efficacy in inhibition
      of these parameters. Renal NADPH oxidase (Nox)1 and Nox2 were significantly
      decreased by aliskiren or paricalcitol alone or in combination, while renal Nox4
      expression was significantly reduced by paricalcitol mono- or combination
      treatment. Increased levels of p-Erk and p-p38 MAPK, and NF-kappaB in UUO kidneys
      were also significantly reduced by either aliskiren or paricalcitol treatment
      alone or in combination. Aliskiren or paricalcitol monotherapy significantly
      reduced the expression of (pro)renin receptor in UUO kidneys. In addition,
      aliskiren tended to augment renin expression in UUO kidneys, but paricalcitol
      reduced its expression level. The combination treatment effectively blocked both
      (pro)renin receptor and renin expression induced by aliskiren, and resulted in a
      further reduction of the renal expression of angiotensin II AT1 receptor.
      Aliskiren failed to increase the expression of vitamin D receptor in UUO kidneys,
      but the combination treatment restored its expression level. Taken together, a
      treatment combining aliskiren with paricalcitol better inhibits UUO-induced renal
      injury. The mechanism of this synergy may involve more profound inhibition of the
      intrarenal renin-angiotensin system.

PMID- 28753621
TI  - Mechanical versus humoral determinants of brain death-induced lung injury.
AB  - BACKGROUND: The mechanisms of brain death (BD)-induced lung injury remain
      incompletely understood, as uncertainties persist about time-course and relative
      importance of mechanical and humoral perturbations. METHODS: Brain death was
      induced by slow intracranial blood infusion in anesthetized pigs after
      randomization to placebo (n = 11) or to methylprednisolone (n = 8) to inhibit the
      expression of pro-inflammatory mediators. Pulmonary artery pressure (PAP), wedged
      PAP (PAWP), pulmonary vascular resistance (PVR) and effective pulmonary capillary
      pressure (PCP) were measured 1 and 5 hours after Cushing reflex. Lung tissue was
      sampled to determine gene expressions of cytokines and oxidative stress
      molecules, and pathologically score lung injury. RESULTS: Intracranial
      hypertension caused a transient increase in blood pressure followed, after brain
      death was diagnosed, by persistent increases in PAP, PCP and the venous component
      of PVR, while PAWP did not change. Arterial PO2/fraction of inspired O2
      (PaO2/FiO2) decreased. Brain death was associated with an accumulation of
      neutrophils and an increased apoptotic rate in lung tissue together with
      increased pro-inflammatory interleukin (IL)-6/IL-10 ratio and increased heme
      oxygenase(HO)-1 and hypoxia inducible factor(HIF)-1 alpha expression. Blood
      expressions of IL-6 and IL-1beta were also increased. Methylprednisolone pre
      treatment was associated with a blunting of increased PCP and PVR venous
      component, which returned to baseline 5 hours after BD, and partially corrected
      lung tissue biological perturbations. PaO2/FiO2 was inversely correlated to PCP
      and lung injury score. CONCLUSIONS: Brain death-induced lung injury may be best
      explained by an initial excessive increase in pulmonary capillary pressure with
      increased pulmonary venous resistance, and was associated with lung activation of
      inflammatory apoptotic processes which were partially prevented by
      methylprednisolone.

PMID- 28753622
TI  - Combined influence of Bt rice and rice dwarf virus on biological parameters of a
      non-target herbivore, Nephotettix cincticeps (Uhler) (Hemiptera: Cicadellidae).
AB  - The advent of genetically modified (GM) Bt rice creates the possibility of
      interactions among Bt crops, crop pathogens and non-target herbivores. In
      particular, information on how pathogen-infected Bt-expressing plants will
      influence non-target herbivores is necessary to predict the sustainability of GM
      cropping systems. Laboratory bioassays were conducted to evaluate the potential
      combined impacts of rice dwarf virus (RDV) and two Bt rice lines, T1C-19 (Cry1C)
      and T2A-1 (Cry2A), on non-target green rice leafhopper (GRLH), Nephotettix
      cincticeps (Uhler) (Hemiptera: Cicadellidae). In the first experiment, GRLHs
      feeding preference tests on Bt rice lines compared to a parental control rice
      line, MH63, were conducted. As rice plants were uninfected with RDV, GRLHs
      generally preferred the control MH63 line over the two Bt lines during the
      initial 8 h, with no significant preference during the following 64 h. As rice
      plants were infected with RDV, there were no clear preferences between the Bt
      rice lines and the control MH63 line. In the second experiment, we assessed the
      combined influence of RDV-infection status and Bt rice lines on GRLH biological
      parameters. Egg duration, adult weights, and male adult longevity were
      significantly affected on RDV-infected Bt rice. Other parameters, egg hatching
      rate, nymph survival and fecundity were not significantly influenced. We infer
      that interaction effect among two testing Bt rice lines and RDV will not lead to
      enlarged pest populations, thus demonstrating that growing these two Bt rice
      lines will poses negligible risk to GRLH in sustainable rice agroecosystems. Long
      term field experiments to monitor the population dynamics of GRLHs at large scale
      need to be carried out to confirm the current results.

PMID- 28753623
TI  - Solution NMR structure of the TRIM21 B-box2 and identification of residues
      involved in its interaction with the RING domain.
AB  - Tripartite motif-containing (TRIM) proteins are defined by the sequential
      arrangement of RING, B-box and coiled-coil domains (RBCC), where the B-box domain
      is a unique feature of the TRIM protein family. TRIM21 is an E3 ubiquitin-protein
      ligase implicated in innate immune signaling by acting as an autoantigen and by
      modifying interferon regulatory factors. Here we report the three-dimensional
      solution structure of the TRIM21 B-box2 domain by nuclear magnetic resonance
      (NMR) spectroscopy. The structure of the B-box2 domain, comprising TRIM21
      residues 86-130, consists of a short alpha-helical segment with an N-terminal
      short beta-strand and two anti-parallel beta-strands jointly found the core, and
      adopts a RING-like fold. This betabetaalphabeta core largely defines the overall
      fold of the TRIM21 B-box2 and the coordination of one Zn2+ ion stabilizes the
      tertiary structure of the protein. Using NMR titration experiments, we have
      identified an exposed interaction surface, a novel interaction patch where the B
      box2 is likely to bind the N-terminal RING domain. Our structure together with
      comparisons with other TRIM B-box domains jointly reveal how its different
      surfaces are employed for various modular interactions, and provides extended
      understanding of how this domain relates to flanking domains in TRIM proteins.

PMID- 28753624
TI  - Muscular fatigue in response to different modalities of CrossFit sessions.
AB  - BACKGROUND: CrossFit is a new strength and conditioning regimen involving short
      intense daily workouts called workouts of the day (WOD). This study assesses
      muscular fatigue levels induced by the three modalities of CrossFit WOD;
      gymnastics (G), metabolic conditioning (M) and weightlifting (W). MATERIAL AND
      METHODS: 34 healthy subjects undertook three WOD (one per week): a G WOD
      consisting of completing the highest number of sets of 5 pull-ups, 10 push-ups
      and 15 air squats in 20 min; an M WOD, in which the maximum number of double
      skipping rope jumps was executed in 8 sets (20 s), resting (10 s) between sets;
      and finally, a W WOD in which the maximum number of power cleans was executed in
      5 min, lifting a load equivalent to 40% of the individual's 1RM. Before and after
      each WOD, blood lactate concentrations were measured. Also, before, during, and
      after each WOD, muscular fatigue was assessed in a countermovement jump test
      (CMJ). RESULTS: Significant reductions were produced in the mechanical variables
      jump height, average power and maximum velocity in response to G; and in jump
      height, mean and peak power, maximum velocity and maximum force in response to W
      (P<0.01). However, in M, significant reductions in mechanical variables were
      observed between pre- and mid session (after sets 2, 4, 6 and 8), but not between
      pre- and post session. CONCLUSIONS: Muscular fatigue, reflected by reduced CMJ
      variables, was produced following the G and W sessions, while recovery of this
      fatigue was observed at the end of M, likely attributable to rest intervals
      allowing for the recovery of phosphocreatine stores. Our findings also suggest
      that the high intensity and volume of exercise in G and W WODs could lead to
      reduced muscular-tendon stiffness causing a loss of jump ability, related here to
      a longer isometric phase during the CMJ.

PMID- 28753625
TI  - Modulation of kanamycin B and kanamycin A biosynthesis in Streptomyces
      kanamyceticus via metabolic engineering.
AB  - Both kanamycin A and kanamycin B, antibiotic components produced by Streptomyces
      kanamyceticus, have medical value. Two different pathways for kanamycin
      biosynthesis have been reported by two research groups. In this study, to obtain
      an optimal kanamycin A-producing strain and a kanamycin B-high-yield strain, we
      first examined the native kanamycin biosynthetic pathway in vivo. Based on the
      proposed parallel biosynthetic pathway, kanN disruption should lead to kanamycin
      A accumulation; however, the kanN-disruption strain produced neither kanamycin A
      nor kanamycin B. We then tested the function of kanJ and kanK. The main
      metabolite of the kanJ-disruption strain was identified as kanamycin B. These
      results clarified that kanamycin biosynthesis does not proceed through the
      parallel pathway and that synthesis of kanamycin A from kanamycin B is catalyzed
      by KanJ and KanK in S. kanamyceticus. As expected, the kanamycin B yield of the
      kanJ-disruption strain was 3268+/-255 MUg/mL, 12-fold higher than that of the
      original strain. To improve the purity of kanamycin A and reduce the yield of
      kanamycin B in the fermentation broth, four different kanJ- and kanK
      overexpressing strains were constructed through either homologous recombination
      or site-specific integration. The overexpressing strain containing three copies
      of kanJ and kanK in its genome exhibited the lowest kanamycin B yield (128+/-20
      MUg/mL), which was 54% lower than that of the original strain. Our experimental
      results demonstrate that kanamycin A is derived from KanJ-and-KanK-catalyzed
      conversion of kanamycin B in S. kanamyceticus. Moreover, based on the clarified
      biosynthetic pathway, we obtained a kanamycin B-high-yield strain and an
      optimized kanamycin A-producing strain with minimal byproduct.

PMID- 28753626
TI  - Reallocating bouted sedentary time to non-bouted sedentary time, light activity
      and moderate-vigorous physical activity in adults with prediabetes and type 2
      diabetes.
AB  - AIM: The aim of this study was to investigate the potential associations of
      reallocating 30 minutes sedentary time in long bouts (>60 min) to sedentary time
      in non-bouts, light intensity physical activity (LPA) and moderate- to vigorous
      physical activity (MVPA) with cardiometabolic risk factors in a population
      diagnosed with prediabetes or type 2 diabetes. METHODS: Participants diagnosed
      with prediabetes and type 2 diabetes (n = 124, 50% men, mean [SD] age = 63.8
      [7.5] years) were recruited to the physical activity intervention Sophia Step
      Study. For this study baseline data was used with a cross-sectional design. Time
      spent in sedentary behaviors in bouts (>60 min) and non-bouts (accrued in <60 min
      bouts) and physical activity was measured using the ActiGraph GT1M. Associations
      of reallocating bouted sedentary time to non-bouted sedentary time, LPA and MVPA
      with cardiometabolic risk factors were examined using an isotemporal substitution
      framework with linear regression models. RESULTS: Reallocating 30 minutes
      sedentary time in bouts to MVPA was associated with lower waist circumference (b
      = -4.30 95% CI:-7.23, -1.38 cm), lower BMI (b = -1.46 95% CI:-2.60, -0.33 kg/m2)
      and higher HDL cholesterol levels (b = 0.11 95% CI: 0.02, 0.21 kg/m2. Similar
      associations were seen for reallocation of sedentary time in non-bouts to MVPA.
      Reallocating sedentary time in bouts to LPA was associated only with lower waist
      circumference. CONCLUSION: Reallocation of sedentary time in bouts as well as non
      bouts to MVPA, but not to LPA, was beneficially associated with waist
      circumference, BMI and HDL cholesterol in individuals with prediabetes and type 2
      diabetes. The results of this study confirm the importance of reallocation
      sedentary time to MVPA.

PMID- 28753628
TI  - A fast and accurate zebra finch syllable detector.
AB  - The song of the adult male zebra finch is strikingly stereotyped. Efforts to
      understand motor output, pattern generation, and learning have taken advantage of
      this consistency by investigating the bird's ability to modify specific parts of
      song under external cues, and by examining timing relationships between neural
      activity and vocal output. Such experiments require that precise moments during
      song be identified in real time as the bird sings. Various syllable-detection
      methods exist, but many require special hardware, software, and know-how, and
      details on their implementation and performance are scarce. We present an
      accurate, versatile, and fast syllable detector that can control hardware at
      precisely timed moments during zebra finch song. Many moments during song can be
      isolated and detected with false negative and false positive rates well under 1%
      and 0.005% respectively. The detector can run on a stock Mac Mini with triggering
      delay of less than a millisecond and a jitter of sigma ~ 2 milliseconds.

PMID- 28753627
TI  - Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease
      through perturbation of a chromatin remodeling protein.
AB  - Mutations in BBS6 cause two clinically distinct syndromes, Bardet-Biedl syndrome
      (BBS), a syndrome caused by defects in cilia transport and function, as well as
      McKusick-Kaufman syndrome, a genetic disorder characterized by congenital heart
      defects. Congenital heart defects are rare in BBS, and McKusick-Kaufman syndrome
      patients do not develop retinitis pigmentosa. Therefore, the McKusick-Kaufman
      syndrome allele may highlight cellular functions of BBS6 distinct from the
      presently understood functions in the cilia. In support, we find that the
      McKusick-Kaufman syndrome disease-associated allele, BBS6H84Y; A242S, maintains
      cilia function. We demonstrate that BBS6 is actively transported between the
      cytoplasm and nucleus, and that BBS6H84Y; A242S, is defective in this transport.
      We developed a transgenic zebrafish with inducible bbs6 to identify novel binding
      partners of BBS6, and we find interaction with the SWI/SNF chromatin remodeling
      protein Smarcc1a (SMARCC1 in humans). We demonstrate that through this
      interaction, BBS6 modulates the sub-cellular localization of SMARCC1 and find, by
      transcriptional profiling, similar transcriptional changes following smarcc1a and
      bbs6 manipulation. Our work identifies a new function for BBS6 in nuclear
      cytoplasmic transport, and provides insight into the disease mechanism underlying
      the congenital heart defects in McKusick-Kaufman syndrome patients.

PMID- 28753629
TI  - How to make complexity look simple? Conveying ecosystems restoration complexity
      for socio-economic research and public engagement.
AB  - Ecosystems degradation represents one of the major global challenges at the
      present time, threating people's livelihoods and well-being worldwide. Ecosystem
      restoration therefore seems no longer an option, but an imperative. Restoration
      challenges are such that a dialogue has begun on the need to re-shape restoration
      as a science. A critical aspect of that reshaping process is the acceptance that
      restoration science and practice needs to be coupled with socio-economic research
      and public engagement. This inescapably means conveying complex ecosystem's
      information in a way that is accessible to the wider public. In this paper we
      take up this challenge with the ultimate aim of contributing to making a step
      change in science's contribution to ecosystems restoration practice. Using
      peatlands as a paradigmatically complex ecosystem, we put in place a
      transdisciplinary process to articulate a description of the processes and
      outcomes of restoration that can be understood widely by the public. We provide
      evidence of the usefulness of the process and tools in addressing four key
      challenges relevant to restoration of any complex ecosystem: (1) how to represent
      restoration outcomes; (2) how to establish a restoration reference; (3) how to
      cope with varying restoration time-lags and (4) how to define spatial units for
      restoration. This evidence includes the way the process resulted in the creation
      of materials that are now being used by restoration practitioners for
      communication with the public and in other research contexts. Our main
      contribution is of an epistemological nature: while ecosystem services-based
      approaches have enhanced the integration of academic disciplines and non
      specialist knowledge, this has so far only followed one direction (from the
      biophysical underpinning to the description of ecosystem services and their
      appreciation by the public). We propose that it is the mix of approaches and
      epistemological directions (including from the public to the biophysical
      parameters) what will make a definitive contribution to restoration practice.

PMID- 28753630
TI  - Double impact: natural molluscicide for schistosomiasis vector control also
      impedes development of Schistosoma mansoni cercariae into adult parasites.
AB  - BACKGROUND: Schistosomiasis has been reported in 78 endemic countries and affects
      240 million people worldwide. The digenetic parasite Schistosoma mansoni needs
      fresh water to compete its life cycle. There, it is susceptible to soluble
      compounds that can affect directly and/or indirectly the parasite's biology. The
      cercariae stage is one of the key points in which the parasite is vulnerable to
      different soluble compounds that can significantly alter the parasite's life
      cycle. Molluscicides are recommended by the World Health Organization for the
      control of schistosomiasis transmission and Euphorbia milii latex is effective
      against snails intermediate hosts. METHODOLOGY/PRINCIPAL FINDINGS: We used
      parasitological tools and electron microscopy to verify the effects of cercariae
      exposure to natural molluscicide (Euphorbia milii latex) on morphology,
      physiology and fitness of adult parasite worms. In order to generate insights
      into key metabolic pathways that lead to the observed phenotypes we used
      comparative transcriptomics and proteomics. CONCLUSIONS/SIGNIFICANCE: We describe
      here that the effect of latex on the adult is not due to direct toxicity but it
      triggers an early change in developmental trajectory and perturbs cell memory,
      mobility, energy metabolism and other key pathways. We conclude that latex has
      not only an effect on the vector but applies also long lasting schistosomastatic
      action. We believe that these results are of interest not only to parasitologists
      since it shows that natural compounds, presumably without side effects, can have
      an impact that occurred unexpectedly on developmental processes. Such collateral
      damage is in this case positive, since it impacts the true target of the
      treatment campaign. This type of treatment could also provide a rational for the
      control of other pests. Our results will contribute to enforce the use of E.
      milii latex in Brazil and other endemic countries as cheap alternative or
      complement to mass drug treatment with Praziquantel, the only available drug to
      cure the patients (without preventing re-infection).

PMID- 28753631
TI  - Enhancement of early warning properties in the Kuramoto model and in an atrial
      fibrillation model due to an external perturbation of the system.
AB  - When a complex dynamical system is externally disturbed, the statistical moments
      of signals associated to it can be affected in ways that depend on the nature and
      amplitude of the perturbation. In systems that exhibit phase transitions, the
      statistical moments can be used as Early Warnings (EW) of the transition. A
      natural question is thus to wonder what effect external disturbances have on the
      EWs of system. In this work we study the impact of external noise added to the
      system on the EWs, with particular focus on understanding the importance of the
      amplitude and complexity of the noise. We do this by analyzing the EWs of two
      computational models related to biology: the Kuramoto model, which is a paradigm
      of synchronization for biological systems, and a cellular automaton model of
      cardiac dynamics which has been used as a model for atrial fibrillation. For each
      model we first characterize the EWs. Then, we introduce external noise of varying
      intensity and nature to observe what effect this has on the EWs. In both cases we
      find that the introduction of noise amplified the EWs, with more complex noise
      having a greater effect. This both offers a way to improve the chance of
      detection of EWs in real systems and suggests that natural variability in the
      real world does not have a detrimental effect on EWs, but the opposite.

PMID- 28753632
TI  - Evolving use of social media among Chinese urologists: Opportunity or challenge?
AB  - BACKGROUND: Social media has revolutionized the way people communicate, and it
      has been widely incorporated into medical practice. However, limited data are
      available regarding the use of social media by Chinese urologists in their
      practice. METHODS: From 2014 to 2016, during the China Urological Association's
      (CUA) Annual National Minimally Invasive Urology Academic Conference, an
      anonymous survey on social media usage was distributed to participant urologists.
      RESULTS: The results of the survey, which was completed by 665 participants,
      indicate a conspicuous increase in social media use during the last three years.
      Regression analysis showed that year (2014 compared to 2016 and 2015), institute
      location (in the eastern region of China) and age (<35 y) were independent
      predictors of social media use. Rather than for personal use, an increasing
      number of respondents said they used social media for professional purposes, and
      for most respondents, social media has had a positive impact on their practice.
      However, when posting information on social media, few respondents were aware of
      the issue of protecting patients' privacy. CONCLUSIONS: Our study demonstrates a
      dramatic increase in social media use among Chinese urologists, which provides
      great opportunities for online academic communication and medical education.
      However, unprofessional use of social media in the medical practice may bring
      about potential risks and challenges for the further development of social media
      in medical practice.

PMID- 28753633
TI  - Patient safety climate profiles across time: Strength and level of safety climate
      associated with a quality improvement program in Switzerland-A cross-sectional
      survey study.
AB  - Safety Climate has been acknowledged as an unspecific factor influencing patient
      safety. However, studies rarely provide in-depth analysis of climate data. As a
      helpful approach, the concept of "climate strength" has been proposed. In the
      present study we tested the hypotheses that even if safety climate remains stable
      on mean-level across time, differences might be evident in strength or shape. The
      data of two hospitals participating in a large national quality improvement
      program were analysed for differences in climate profiles at two measurement
      occasions. We analysed differences on mean-level, differences in percent
      problematic response, agreement within groups, and frequency histograms in two
      large hospitals in Switzerland at two measurement occasions (2013 and 2015)
      applying the Safety Climate Survey. In total, survey responses of 1193
      individuals were included in the analyses. Overall, small but significant
      differences on mean-level of safety climate emerged for some subgroups. Also,
      although agreement was strong at both time-points within groups, tendencies of
      divergence or consensus were present in both hospitals. Depending on subgroup and
      analyses chosen, differences were more or less pronounced. The present study
      illustrated that taking several measures into account and describing safety
      climate from different perspectives is necessary in order to fully understand
      differences and trends within groups and to develop interventions addressing the
      needs of different groups more precisely.

PMID- 28753634
TI  - Dissociating error-based and reinforcement-based loss functions during
      sensorimotor learning.
AB  - It has been proposed that the sensorimotor system uses a loss (cost) function to
      evaluate potential movements in the presence of random noise. Here we test this
      idea in the context of both error-based and reinforcement-based learning. In a
      reaching task, we laterally shifted a cursor relative to true hand position using
      a skewed probability distribution. This skewed probability distribution had its
      mean and mode separated, allowing us to dissociate the optimal predictions of an
      error-based loss function (corresponding to the mean of the lateral shifts) and a
      reinforcement-based loss function (corresponding to the mode). We then examined
      how the sensorimotor system uses error feedback and reinforcement feedback, in
      isolation and combination, when deciding where to aim the hand during a reach. We
      found that participants compensated differently to the same skewed lateral shift
      distribution depending on the form of feedback they received. When provided with
      error feedback, participants compensated based on the mean of the skewed noise.
      When provided with reinforcement feedback, participants compensated based on the
      mode. Participants receiving both error and reinforcement feedback continued to
      compensate based on the mean while repeatedly missing the target, despite
      receiving auditory, visual and monetary reinforcement feedback that rewarded
      hitting the target. Our work shows that reinforcement-based and error-based
      learning are separable and can occur independently. Further, when error and
      reinforcement feedback are in conflict, the sensorimotor system heavily weights
      error feedback over reinforcement feedback.

PMID- 28753635
TI  - Assessing the ecological vulnerability of the upper reaches of the Minjiang
      River.
AB  - The upper reaches of the Minjiang River (URMR), located on the eastern edge of
      the Tibetan Plateau in southwestern China, are an important component of the
      ecological barrier of the Upper Yangtze River Basin. Climate change and human
      activities have increased the ecological sensitivity and vulnerability of the
      region, which may pose a threat to the ecological security of the Yangtze River
      Basin and have negative impacts on local social and economic development. In this
      study, we analyzed land use and cover change (LUCC) of the URMR between 2000 and
      2010, and found that the total rate of LUCC was less than 0.50% during this
      period. In addition, net primary production (NPP) was employed to describe the
      changes in ecosystem sensitivity and vulnerability, and the results demonstrated
      that slightly and moderately sensitive and vulnerable zones occupied the largest
      area, distributed mainly in forest, shrub, and grassland ecosystems. However,
      compared with the period from 2000 to 2005, the ecological sensitivity and
      vulnerability showed a worsening trend in the period 2005-2010. Exploring the
      relationship between vulnerability/sensitivity and environmental factors, we
      found that sensitivity and vulnerability were positively correlated with
      precipitation (>700 mm) and aridity index (>36 mm/ degrees C). The results
      highlight that the future ecological sensitivity and vulnerability of URMR should
      be further investigated, and that the LUCC induced by human activities and
      climate change have caused alteration of in ecosystem vulnerability.

PMID- 28753636
TI  - Comparison of segmental spinal movement control in adolescents with and without
      idiopathic scoliosis using modified pressure biofeedback unit.
AB  - BACKGROUND: Postural rehabilitation emphasizing on motor control training of
      segmental spinal movements has been proposed to effectively reduce the scoliotic
      spinal deformities in adolescent idiopathic scoliosis (AIS). However, information
      regarding the impairments of segmental spinal movement control involving
      segmental spinal stabilizers in adolescent idiopathic scoliosis remains limited.
      Examination of segmental spinal movement control may provide a window for
      investigating the features of impaired movement control specific to spinal
      segments that may assist in the development of physiotherapeutic management of
      AIS. OBJECTIVES: To compare segmental spinal movement control in adolescents with
      and without idiopathic scoliosis using modified pressure biofeedback unit.
      METHODS: Segmental spinal movement control was assessed in twenty adolescents
      with idiopathic scoliosis (AISG) and twenty healthy adolescents (CG) using a
      modified pressure biofeedback unit. Participants performed segmental spinal
      movements that primarily involved segmental spinal stabilizing muscles with
      graded and sustained muscle contraction against/off a pressure cuff from baseline
      to target pressures and then maintained for 1 min. Pressure data during the 1
      minute maintenance phase were collected for further analysis. Pressure deviation
      were calculated and compared between groups. RESULTS: The AISG had significantly
      greater pressure deviations for all segmental spinal movements of cervical,
      thoracic, and lumbar spine than the CG. CONCLUSION: Pressure biofeedback unit was
      feasible for assessing segmental spinal movement control in AIS. AISG exhibited
      poorer ability to grade and sustain muscle activities for local movements of
      cervical, thoracic, and lumbar spine, suggesting motor control training of
      segmental spinal movements involving segmental spinal stabilizing muscles on
      frontal, sagittal, and transverse planes were required.

PMID- 28753638
TI  - 3D printing scanning electron microscopy sample holders: A quick and cost
      effective alternative for custom holder fabrication.
AB  - A simple and cost effective alternative for fabricating custom Scanning Electron
      Microscope (SEM) sample holders using 3D printers and conductive polylactic acid
      filament is presented. The flexibility of the 3D printing process allowed for the
      fabrication of sample holders with specific features that enable the high
      resolution imaging of nanoelectrodes and nanopipettes. The precise value of the
      inner semi cone angle of the nanopipettes taper was extracted from the acquired
      images and used for calculating their radius using electrochemical methods.
      Because of the low electrical resistivity presented by the 3D printed holder, the
      imaging of non-conductive nanomaterials, such as alumina powder, was found to be
      possible. The fabrication time for each sample holder was under 30 minutes and
      the average cost was less than $0.50 per piece. Despite being quick and
      economical to fabricate, the sample holders were found to be sufficiently
      resistant, allowing for multiple uses of the same holder.

PMID- 28753637
TI  - Collaborative update of a rule-based expert system for HIV-1 genotypic resistance
      test interpretation.
AB  - INTRODUCTION: HIV-1 genotypic resistance test (GRT) interpretation systems (IS)
      require updates as new studies on HIV-1 drug resistance are published and as
      treatment guidelines evolve. METHODS: An expert panel was created to provide
      recommendations for the update of the Stanford HIV Drug Resistance Database
      (HIVDB) GRT-IS. The panel was polled on the ARVs to be included in a GRT report,
      and the drug-resistance interpretations associated with 160 drug-resistance
      mutation (DRM) pattern-ARV combinations. The DRM pattern-ARV combinations
      included 52 nucleoside RT inhibitor (NRTI) DRM pattern-ARV combinations (13
      patterns x 4 NRTIs), 27 nonnucleoside RT inhibitor (NNRTI) DRM pattern-ARV
      combinations (9 patterns x 3 NNRTIs), 39 protease inhibitor (PI) DRM pattern-ARV
      combinations (13 patterns x 3 PIs) and 42 integrase strand transfer inhibitor
      (INSTI) DRM pattern-ARV combinations (14 patterns x 3 INSTIs). RESULTS: There was
      universal agreement that a GRT report should include the NRTIs lamivudine,
      abacavir, zidovudine, emtricitabine, and tenofovir disoproxil fumarate; the
      NNRTIs efavirenz, etravirine, nevirapine, and rilpivirine; the PIs atazanavir/r,
      darunavir/r, and lopinavir/r (with "/r" indicating pharmacological boosting with
      ritonavir or cobicistat); and the INSTIs dolutegravir, elvitegravir, and
      raltegravir. There was a range of opinion as to whether the NRTIs stavudine and
      didanosine and the PIs nelfinavir, indinavir/r, saquinavir/r, fosamprenavir/r,
      and tipranavir/r should be included. The expert panel members provided highly
      concordant DRM pattern-ARV interpretations with only 6% of NRTI, 6% of NNRTI, 5%
      of PI, and 3% of INSTI individual expert interpretations differing from the
      expert panel median by more than one resistance level. The expert panel median
      differed from the HIVDB 7.0 GRT-IS for 20 (12.5%) of the 160 DRM pattern-ARV
      combinations including 12 NRTI, two NNRTI, and six INSTI pattern-ARV
      combinations. Eighteen of these differences were updated in HIVDB 8.1 GRT-IS to
      reflect the expert panel median. Additionally, HIVDB users are now provided with
      the option to exclude those ARVs not considered to be universally required.
      CONCLUSIONS: The HIVDB GRT-IS was updated through a collaborative process to
      reflect changes in HIV drug resistance knowledge, treatment guidelines, and
      expert opinion. Such a process broadens consensus among experts and identifies
      areas requiring further study.

PMID- 28753639
TI  - Self-regulation strategy, feedback timing and hemodynamic properties modulate
      learning in a simulated fMRI neurofeedback environment.
AB  - Direct manipulation of brain activity can be used to investigate causal brain
      behavior relationships. Current noninvasive neural stimulation techniques are too
      coarse to manipulate behaviors that correlate with fine-grained spatial patterns
      recorded by fMRI. However, these activity patterns can be manipulated by having
      people learn to self-regulate their own recorded neural activity. This technique,
      known as fMRI neurofeedback, faces challenges as many participants are unable to
      self-regulate. The causes of this non-responder effect are not well understood
      due to the cost and complexity of such investigation in the MRI scanner. Here, we
      investigated the temporal dynamics of the hemodynamic response measured by fMRI
      as a potential cause of the non-responder effect. Learning to self-regulate the
      hemodynamic response involves a difficult temporal credit-assignment problem
      because this signal is both delayed and blurred over time. Two factors critical
      to this problem are the prescribed self-regulation strategy (cognitive or
      automatic) and feedback timing (continuous or intermittent). Here, we sought to
      evaluate how these factors interact with the temporal dynamics of fMRI without
      using the MRI scanner. We first examined the role of cognitive strategies by
      having participants learn to regulate a simulated neurofeedback signal using a
      unidimensional strategy: pressing one of two buttons to rotate a visual grating
      that stimulates a model of visual cortex. Under these conditions, continuous
      feedback led to faster regulation compared to intermittent feedback. Yet, since
      many neurofeedback studies prescribe implicit self-regulation strategies, we
      created a computational model of automatic reward-based learning to examine
      whether this result held true for automatic processing. When feedback was delayed
      and blurred based on the hemodynamics of fMRI, this model learned more reliably
      from intermittent feedback compared to continuous feedback. These results suggest
      that different self-regulation mechanisms prefer different feedback timings, and
      that these factors can be effectively explored and optimized via simulation prior
      to deployment in the MRI scanner.

PMID- 28753640
TI  - Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the
      putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial
      growth.
AB  - We have previously shown that the Mycobacterium tuberculosis universal stress
      protein Rv2623 regulates mycobacterial growth and may be required for the
      establishment of tuberculous persistence. Here, yeast two-hybrid and affinity
      chromatography experiments have demonstrated that Rv2623 interacts with one of
      the two forkhead-associated domains (FHA I) of Rv1747, a putative ATP-binding
      cassette transporter annotated to export lipooligosaccharides. FHA domains are
      signaling protein modules that mediate protein-protein interactions to modulate a
      wide variety of biological processes via binding to conserved phosphorylated
      threonine (pT)-containing oligopeptides of the interactors. Biochemical,
      immunochemical and mass spectrometric studies have shown that Rv2623 harbors pT
      and specifically identified threonine 237 as a phosphorylated residue. Relative
      to wild-type Rv2623 (Rv2623WT), a mutant protein in which T237 has been replaced
      with a non-phosphorylatable alanine (Rv2623T237A) exhibits decreased interaction
      with the Rv1747 FHA I domain and diminished growth-regulatory capacity.
      Interestingly, compared to WT bacilli, an M. tuberculosis Rv2623 null mutant
      (DeltaRv2623) displays enhanced expression of phosphatidyl-myo-inositol
      mannosides (PIMs), while the DeltaRv1747 mutant expresses decreased levels of
      PIMs. Animal studies have previously shown that DeltaRv2623 is hypervirulent,
      while DeltaRv1747 is growth-attenuated. Collectively, these data have provided
      evidence that Rv2623 interacts with Rv1747 to regulate mycobacterial growth; and
      this interaction is mediated via the recognition of the conserved Rv2623 pT237
      containing FHA-binding motif by the Rv1747 FHA I domain. The divergent aberrant
      PIM profiles and the opposing in vivo growth phenotypes of DeltaRv2623 and
      DeltaRv1747, together with the annotated lipooligosaccharide exporter function of
      Rv1747, suggest that Rv2623 interacts with Rv1747 to modulate mycobacterial
      growth by negatively regulating the activity of Rv1747; and that Rv1747 might
      function as a transporter of PIMs. Because these glycolipids are major
      mycobacterial cell envelope components that can impact on the immune response,
      our findings raise the possibility that Rv2623 may regulate bacterial growth,
      virulence, and entry into persistence, at least in part, by modulating the levels
      of bacillary PIM expression, perhaps through negatively regulating the Rv1747
      dependent export of the immunomodulatory PIMs to alter host-pathogen interaction,
      thereby influencing the fate of M. tuberculosis in vivo.

PMID- 28753641
TI  - UV-Vis and ATR-FTIR spectroscopic investigations of postmortem interval based on
      the changes in rabbit plasma.
AB  - Estimating PMI is of great importance in forensic investigations. Although many
      methods are used to estimate the PMI, a few investigations focus on the
      postmortem redistribution. In this study, ultraviolet-visible (UV-Vis)
      measurement combined with visual inspection indicated a regular diffusion of
      hemoglobin into plasma after death showing the redistribution of postmortem
      components in blood. Thereafter, attenuated total reflection-Fourier transform
      infrared (ATR-FTIR) spectroscopy was used to confirm the variations caused by
      this phenomenon. First, full-spectrum partial least-squares (PLS) and genetic
      algorithm combined with PLS (GA-PLS) models were constructed to predict the PMI.
      The performance of GA-PLS model was better than that of full-spectrum PLS model
      based on its root mean square error (RMSE) of cross-validation of 3.46 h (R2 =
      0.95) and the RMSE of prediction of 3.46 h (R2 = 0.94). The investigation on the
      similarity of spectra between blood plasma and formed elements also supported the
      role of redistribution of components in spectral changes in postmortem plasma.
      These results demonstrated that ATR-FTIR spectroscopy coupled with the advanced
      mathematical methods could serve as a convenient and reliable tool to study the
      redistribution of postmortem components and estimate the PMI.

PMID- 28753642
TI  - Dengue subgenomic flaviviral RNA disrupts immunity in mosquito salivary glands to
      increase virus transmission.
AB  - Globally re-emerging dengue viruses are transmitted from human-to-human by Aedes
      mosquitoes. While viral determinants of human pathogenicity have been defined,
      there is a lack of knowledge of how dengue viruses influence mosquito
      transmission. Identification of viral determinants of transmission can help
      identify isolates with high epidemiological potential. Additionally, mechanistic
      understanding of transmission will lead to better understanding of how dengue
      viruses harness evolution to cycle between the two hosts. Here, we identified
      viral determinants of transmission and characterized mechanisms that enhance
      production of infectious saliva by inhibiting immunity specifically in salivary
      glands. Combining oral infection of Aedes aegypti mosquitoes and reverse
      genetics, we identified two 3' UTR substitutions in epidemic isolates that
      increased subgenomic flaviviral RNA (sfRNA) quantity, infectious particles in
      salivary glands and infection rate of saliva, which represents a measure of
      transmission. We also demonstrated that various 3'UTR modifications similarly
      affect sfRNA quantity in both whole mosquitoes and human cells, suggesting a
      shared determinism of sfRNA quantity. Furthermore, higher relative quantity of
      sfRNA in salivary glands compared to midgut and carcass pointed to sfRNA function
      in salivary glands. We showed that the Toll innate immune response was
      preferentially inhibited in salivary glands by viruses with the 3'UTR
      substitutions associated to high epidemiological fitness and high sfRNA quantity,
      pointing to a mechanism for higher saliva infection rate. By determining that
      sfRNA is an immune suppressor in a tissue relevant to mosquito transmission, we
      propose that 3'UTR/sfRNA sequence evolution shapes dengue epidemiology not only
      by influencing human pathogenicity but also by increasing mosquito transmission,
      thereby revealing a viral determinant of epidemiological fitness that is shared
      between the two hosts.

PMID- 28753643
TI  - Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy
      and tolerability endpoints from two large global cardiovascular outcomes trials
      for darapladib.
AB  - Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, failed
      to demonstrate efficacy for the primary endpoints in two large phase III
      cardiovascular outcomes trials, one in stable coronary heart disease patients
      (STABILITY) and one in acute coronary syndrome (SOLID-TIMI 52). No major safety
      signals were observed but tolerability issues of diarrhea and odor were common
      (up to 13%). We hypothesized that genetic variants associated with Lp-PLA2
      activity may influence efficacy and tolerability and therefore performed a
      comprehensive pharmacogenetic analysis of both trials. We genotyped patients
      within the STABILITY and SOLID-TIMI 52 trials who provided a DNA sample and
      consent (n = 13,577 and 10,404 respectively, representing 86% and 82% of the
      trial participants) using genome-wide arrays with exome content and performed
      imputation using a 1000 Genomes reference panel. We investigated baseline and
      change from baseline in Lp-PLA2 activity, two efficacy endpoints (major coronary
      events and myocardial infarction) as well as tolerability parameters at genome
      wide and candidate gene level using a meta-analytic approach. We replicated
      associations of published loci on baseline Lp-PLA2 activity (APOE, CELSR2, LPA,
      PLA2G7, LDLR and SCARB1) and identified three novel loci (TOMM5, FRMD5 and LPL)
      using the GWAS-significance threshold P<=5E-08. Review of the PLA2G7 gene
      (encoding Lp-PLA2) within these datasets identified V279F null allele carriers as
      well as three other rare exonic null alleles within various ethnic groups,
      however none of these variants nor any other loci associated with Lp-PLA2
      activity at baseline were associated with any of the drug response endpoints. The
      analysis of darapladib efficacy endpoints, despite low power, identified six low
      frequency loci with main genotype effect (though with borderline imputation
      scores) and one common locus (minor allele frequency 0.24) with genotype by
      treatment interaction effect passing the GWAS-significance threshold. This locus
      conferred risk in placebo subjects, hazard ratio (HR) 1.22 with 95% confidence
      interval (CI) 1.11-1.33, but was protective in darapladib subjects, HR 0.79 (95%
      CI 0.71-0.88). No major loci for tolerability were found. Thus, genetic analysis
      confirmed and extended the influence of lipoprotein loci on Lp-PLA2 levels,
      identified some novel null alleles in the PLA2G7 gene, and only identified one
      potentially efficacious subgroup within these two large clinical trials.

PMID- 28753644
TI  - E pluribus unum: Harmonization of physical functioning across intervention
      studies of middle-aged and older adults.
AB  - Common scales for physical functioning are not directly comparable without
      harmonization techniques, complicating attempts to pool data across studies. Our
      aim was to provide a standardized metric for physical functioning in adults based
      on basic and instrumental activities of daily living scaled to NIH PROMIS norms.
      We provide an item bank to compare the difficulty of various physical functioning
      activities. We used item response theory methods to place 232 basic and
      instrumental activities of daily living questions, administered across eight
      intervention studies of middle-aged and older adults (N = 2,556), on a common
      metric. We compared the scale's precision to an average z-score of items and
      evaluated criterion validity based on objective measures of physical functioning
      and Fried's frailty criteria. Model-estimated item thresholds were widely
      distributed across the range of physical functioning. From test information
      plots, the lowest precision in each dataset was 0.80. Using power calculations,
      the sample size needed to detect 25% physical functional decline with 80% power
      based on the physical functioning factor was less than half of what would be
      needed using an average z-score. The physical functioning factor correlated in
      expected directions with objective measurements from the Timed Up and Go task,
      tandem balance, gait speed, chair stands, grip strength, and frailty status. Item
      level harmonization enables direct comparison of physical functioning measures
      across existing and potentially future studies and across levels of function
      using a nationally representative metric. We identified key thresholds of
      physical functioning items in an item bank to facilitate clinical and
      epidemiologic decision-making.

PMID- 28753645
TI  - Developmental morphology of cover crop species exhibit contrasting behaviour to
      changes in soil bulk density, revealed by X-ray computed tomography.
AB  - Plant roots growing through soil typically encounter considerable structural
      heterogeneity, and local variations in soil dry bulk density. The way the in situ
      architecture of root systems of different species respond to such heterogeneity
      is poorly understood due to challenges in visualising roots growing in soil. The
      objective of this study was to visualise and quantify the impact of abrupt
      changes in soil bulk density on the roots of three cover crop species with
      contrasting inherent root morphologies, viz. tillage radish (Raphanus sativus),
      vetch (Vicia sativa) and black oat (Avena strigosa). The species were grown in
      soil columns containing a two-layer compaction treatment featuring a 1.2 g cm-3
      (uncompacted) zone overlaying a 1.4 g cm-3 (compacted) zone. Three-dimensional
      visualisations of the root architecture were generated via X-ray computed
      tomography, and an automated root-segmentation imaging algorithm. Three classes
      of behaviour were manifest as a result of roots encountering the compacted
      interface, directly related to the species. For radish, there was switch from a
      single tap-root to multiple perpendicular roots which penetrated the compacted
      zone, whilst for vetch primary roots were diverted more horizontally with limited
      lateral growth at less acute angles. Black oat roots penetrated the compacted
      zone with no apparent deviation. Smaller root volume, surface area and lateral
      growth were consistently observed in the compacted zone in comparison to the
      uncompacted zone across all species. The rapid transition in soil bulk density
      had a large effect on root morphology that differed greatly between species, with
      major implications for how these cover crops will modify and interact with soil
      structure.

PMID- 28753646
TI  - Associations between self-reported diabetes and 78 circulating markers of
      inflammation, immunity, and metabolism among adults in the United States.
AB  - Inflammation is increasingly thought to be associated with diabetes; however,
      only a few inflammation markers have been assessed concurrently in relation to
      history of diabetes. In the most comprehensive evaluation of inflammation markers
      and diabetes to date using a Luminex bead-based assay, we measured 78
      inflammation-, immune-, and metabolic-related markers detectable in at least 10%
      of serum samples collected from participants from the Prostate, Lung, Colorectal
      and Ovarian Cancer (PLCO) screening trial (n = 1,814). At baseline, 6.6% (n =
      120) of PLCO participants self-reported a history of diabetes. Cross-sectional
      associations between these markers and self-reported diabetes were assessed using
      weighted logistic regression adjusting for sex, smoking status, blood draw age
      and year, body mass index, and cohort sub-study. Including chemokines [C-C motif
      ligand (CCL) 19, CCL20, CCL21, C-X-C motif ligand (CXCL) 6, CXCL10, and CXCL11]
      and soluble cytokine and chemokine receptors [soluble (s) interleukin (IL) 6
      receptor (R), soluble tumor necrosis factor receptor (sTNFR) 1, sTNFR2, and sIL
      R2], ten inflammation-related markers, were nominally associated with diabetes
      (P<0.05). In addition to these associations, higher levels of insulin, gastric
      inhibitory polypeptide, and pancreatic polypeptide remained significantly
      associated with self-reported diabetes with a false discovery rate <5%,
      indicating that the assay was able to detect markers associated with diabetes. In
      summary, self-reported diabetes was nominally associated with circulating
      cytokines, chemokines, and soluble cytokine and chemokine receptors in the most
      expansive examination of diabetes and inflammation- and immune-related markers to
      date. These results highlight the need to explore in future prospective studies
      the role of inflammation markers in diabetes.

PMID- 28753647
TI  - Incorporating seascape connectivity in conservation prioritisation.
AB  - In conservation prioritisation, it is often implicit that representation targets
      for individual habitat types act as surrogates for the species that inhabit them.
      Yet for many commercially and ecologically important coral reef fish species,
      connectivity among different habitats in a seascape may be more important than
      any single habitat alone. Approaches to conservation prioritisation that consider
      seascape connectivity are thus warranted. I demonstrate an approach that can be
      implemented within a relatively data-poor context, using widely available
      conservation planning software. Based on clearly stated assumptions regarding
      species' habitat usage and movement ability, this approach can be adapted to
      different focal species and contexts, or refined as further data become
      available. I first derive a seascape connectivity metric based on area-weighted
      proximity between juvenile and adult habitat patches, and then apply this during
      spatial prioritisation using the decision-support software Marxan. Using a case
      study from Micronesia, I present two applications: first, to inform
      prioritisation for a network of marine protected areas to achieve regional
      objectives for habitat representation; and second, to identify nursery habitat
      patches that are most likely to supply juveniles to adult populations on reefs
      within existing protected areas. Incorporating seascape connectivity in
      conservation prioritisation highlights areas where small marine protected areas
      placed on coral reefs might benefit from proximity to other habitats in the
      seascape, and thus be more effective. Within the context of community tenure over
      resources, identification of critical nursery habitats to improve the
      effectiveness of existing marine protected areas indicates where collaboration
      across community boundaries might be required. Outputs from these analyses are
      likely to be most useful in regions where management is highly decentralised,
      imposing spatial constraints on the size of individual protected areas.

PMID- 28753648
TI  - Lipoxin A4 encapsulated in PLGA microparticles accelerates wound healing of skin
      ulcers.
AB  - Lipoxin A4 (LXA4) is involved in the resolution of inflammation and wound
      healing; however, it is extremely unstable. Thus, to preserve its biological
      activities and confer stability, we encapsulated LXA4 in poly-lactic-co-glycolic
      acid (PLGA) microparticles (LXA4-MS) and assessed its application in treating
      dorsal rat skin lesions. Ulcers were sealed with fibrin adhesive and treated with
      either LXA4-MS, unloaded microparticles (Un-MS), soluble LXA4, or PBS/glue
      (vehicle). All groups were compared at 0, 2, 7, and 14 days post-lesions. Our
      results revealed that LXA4-MS accelerated wound healing from day 7 and reduced
      initial ulcer diameters by 80%. Soluble LXA4, Un-MS, or PBS closed wounds by 60%,
      45%, and 39%, respectively. LXA4-MS reduced IL-1beta and TNF-alpha, but increased
      TGF-beta, collagen deposition, and the number of blood vessels. Compared to other
      treatments, LXA4-MS reduced inflammatory cell numbers, myeloperoxidase (MPO)
      concentration, and metalloproteinase-8 (MMP8) mRNA in scar tissue, indicating
      decreased neutrophil chemotaxis. In addition, LXA4-MS treatment increased
      macrophages and IL-4, suggesting a positive impact on wound healing. Finally, we
      demonstrated that WRW4, a selective LXA4 receptor (ALX) antagonist, reversed
      healing by 50%, indicating that LXA4 must interact with ALX to induce wound
      healing. Our results show that LXA4-MS could be used as a pharmaceutical
      formulation for the treatment of skin ulcers.

PMID- 28753649
TI  - Pregnant women carrying female fetuses are at higher risk of placental malaria
      infection.
AB  - BACKGROUND: The pathophysiology of the placental malaria is not fully understood.
      If there is a fetal sex-specific susceptibility to malaria infection, this might
      add to the previous knowledge on the immunology, endocrinology and
      pathophysiology of placental malaria infections. AIMS: This study was conducted
      to assess whether the sex of the fetus was associated with placental malaria
      infections. SUBJECTS AND METHODS: A cross-sectional study was performed including
      a secondary analysis of a cohort of women who were investigated for prevalence
      and risk factors (including fetal sex) for placental malaria in eastern Sudan.
      Placental histology was used to diagnose placental malaria infections. RESULTS:
      Among 339 women enrolled, the mean (SD) age was 25.8 (6.7) years and parity was
      2.7 (2.2). Among the new born babies, 157 (46.3%) were male and 182 (53.7%) were
      female. Five (1.5%), 9 (2.7%) and 103 (30.4%) of the 339 placentas had active,
      active-chronic, past-chronic malaria infection on histopathology examination
      respectively, while 222 (65.5%) of them showed no malaria infection. Logistic
      regression analyses showed no associations between maternal age or parity and
      placental malaria infections. Women who have blood group O (OR = 1.95, 95% CI =
      1.19-3.10; P = 0.007) and women who had female new born were at higher risk for
      placental malaria infections (OR = 2.55, 95% CI = 1.57-4.13; P< 0.001).
      CONCLUSION: Fetal gender may be a novel risk factor for placental malaria. In
      this work the female placentas were at higher risk for malaria infections than
      the male placentas.

PMID- 28753650
TI  - NF-kappa B activation correlates with disease phenotype in Crohn's disease.
AB  - BACKGROUND/AIMS: Unregulated activation of nuclear factor-kappaB (NF-kappaB)
      plays a critical role in the pathogenesis of Crohn's disease. In this study, we
      investigated the clinical characteristics and disease outcome of Crohn's disease
      patients with varying levels of the NF-kappaB activation. METHODS: Crohn's
      disease patients who underwent surgical bowel resection were divided into two
      groups, based on the activation status of NF-kappaB. NF-kappaB activation was
      assessed by the immunoreactivity of nuclear NF-kappaB during immunohistochemical
      staining of bowel resection specimens. We compared the demographic, clinical and
      histologic characteristics between groups. Furthermore, the occurrence of
      reoperation, readmission, and medication change due to disease flare-up were
      investigated according to NF-kappaB activation status. RESULTS: Among 83 Crohn's
      disease patients, 47 (56%) showed high NF-kappaB activity and 36 (44%) showed low
      NF-kappaB activity. Patients with high NF-kappaB activity had higher frequency of
      ileocolonic involvement (P = 0.028) and lower frequency of perianal involvement
      (P = 0.042) relative to those with low NF-kappaB activity. Total histologic
      scores were significantly higher in patients with high NF-kappaB activity than
      those with low NF-kappaB activity (P = 0.044). There was no significant
      difference in the frequency of reoperation, readmission, and medication change in
      relation to NF-kappaB activation status. CONCLUSIONS: Crohn's disease patients
      with high NF-kappaB activation showed specific clinical manifestations of higher
      frequency of ileocolonic involvement and lower frequency of perianal involvement
      relative to those with low NF-kappaB activation. High NF-kappaB activity was
      associated with higher histologic scores. However, the NF-kappaB activity did not
      affect the outcome and disease course after surgery.

PMID- 28753651
TI  - Schistosome egg antigens, including the glycoprotein IPSE/alpha-1, trigger the
      development of regulatory B cells.
AB  - Infection with the helminth Schistosoma (S.) mansoni drives the development of
      interleukin (IL)-10-producing regulatory B (Breg) cells in mice and man, which
      have the capacity to reduce experimental allergic airway inflammation and are
      thus of high therapeutic interest. However, both the involved antigen and
      cellular mechanisms that drive Breg cell development remain to be elucidated.
      Therefore, we investigated whether S. mansoni soluble egg antigens (SEA) directly
      interact with B cells to enhance their regulatory potential, or act indirectly on
      B cells via SEA-modulated macrophage subsets. Intraperitoneal injections of S.
      mansoni eggs or SEA significantly upregulated IL-10 and CD86 expression by
      marginal zone B cells. Both B cells as well as macrophages of the splenic
      marginal zone efficiently bound SEA in vivo, but macrophages were dispensable for
      Breg cell induction as shown by macrophage depletion with clodronate liposomes.
      SEA was internalized into acidic cell compartments of B cells and induced a 3
      fold increase of IL-10, which was dependent on endosomal acidification and was
      further enhanced by CD40 ligation. IPSE/alpha-1, one of the major antigens in
      SEA, was also capable of inducing IL-10 in naive B cells, which was reproduced by
      tobacco plant-derived recombinant IPSE. Other major schistosomal antigens, omega
      1 and kappa-5, had no effect. SEA depleted of IPSE/alpha-1 was still able to
      induce Breg cells indicating that SEA contains more Breg cell-inducing
      components. Importantly, SEA- and IPSE-induced Breg cells triggered regulatory T
      cell development in vitro. SEA and recombinant IPSE/alpha-1 also induced IL-10
      production in human CD1d+ B cells. In conclusion, the mechanism of S. mansoni
      induced Breg cell development involves a direct targeting of B cells by SEA
      components such as the secretory glycoprotein IPSE/alpha-1.

PMID- 28753652
TI  - The phosphodiesterase inhibitor, ibudilast, attenuates neuroinflammation in the
      MPTP model of Parkinson's disease.
AB  - BACKGROUND/AIMS: Since the degeneration of the nigrostriatal dopaminergic pathway
      in Parkinson's disease (PD) is associated with the inflammation process and
      decreased levels of cyclic nucleotides, inhibition of up-regulated cyclic
      nucleotide phosphodiesterases (PDEs) appears to be a promising therapeutic
      strategy. We used ibudilast (IBD), a non-selective PDE3,4,10,11 inhibitor, due to
      the abundant PDE 4 and 10 expression in the striatum. The present study for the
      first time examined the efficacy of IBD in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) mouse model of PD. METHODS: IBD [0, 20, 30, 40, or 50
      mg/kg] was injected b.i.d. subcutaneously for nine days to three-month-old male
      C57Bl/10Tar mice, beginning two days prior to MPTP (60 mg/kg) intoxication. High
      pressure liquid chromatography, Western blot analysis, and real time RT-PCR
      methods were applied. RESULTS: Our study demonstrated that chronic administration
      of IBD attenuated astroglial reactivity and increased glial cell-derived
      neurotrophic factor (GDNF) production in the striatum. Moreover, IBD reduced TNF
      alpha, IL-6, and IL-1beta expression. CONCLUSION: IBD had a well-defined effect
      on astroglial activation in the mouse model of PD; however, there was no
      protective effect in the acute phase of injury. Diminished inflammation and an
      increased level of GDNF may provide a better outcome in the later stages of
      neurodegeneration.

PMID- 28753653
TI  - Induction of Sphk1 activity in obese adipose tissue macrophages promotes
      survival.
AB  - During obesity, adipose tissue macrophages (ATM) are increased in concert with
      local inflammation and insulin resistance. Since the levels of sphingolipid (SLs)
      in adipose tissue (AT) are altered during obesity we investigated the potential
      impact of SLs on ATMs. For this, we first analyzed expression of SL metabolizing
      genes in ATMs isolated from obese mice. A marked induction of sphingosine kinase
      1 (Sphk1) expression was observed in obese ATM when compared to lean ATM. This
      induction was observed in both MGL-ve (M1) and MGL1+ve (M2) macrophages from
      obese WAT. Next, RAW264.7 cells were exposed to excessive palmitate, resulting in
      a similar induction of Sphk1. This Sphk1 induction was also observed when cells
      were treated with chloroquine, a lysosomotropic amine impacting lysosome
      function. Simultaneous incubation of RAW cells with palmitate and the Sphk1
      inhibitor SK1-I promoted cell death, suggesting a protective role of Sphk1 during
      lipotoxic conditions. Interestingly, a reduction of endoplasmic reticulum (ER)
      stress related genes was detected in obese ATM and was found to be associated
      with elevated Sphk1 expression. Altogether, our data suggest that lipid overload
      in ATM induces Sphk1, which promotes cell viability.

PMID- 28753654
TI  - Medical treatment of second-trimester fetal miscarriage; A retrospective
      analysis.
AB  - OBJECTIVES: Research on the treatment of second-trimester miscarriages is scarce.
      We studied the outcomes, and the factors associated with adverse events and need
      for hospital resources in the medical treatment of second-trimester miscarriage.
      MATERIALS AND METHODS: In these retrospective analyses we studied women treated
      for spontaneous fetal miscarriage with misoprostol-only (n = 24) or mifepristone
      and misoprostol (n = 177) in duration of gestation 12+1-21+6. Primary outcomes
      were the risk factors for surgical evacuation and excessive bleeding. Secondary
      outcomes were total misoprostol dose, time to expulsion and the length of
      hospital stay. RESULTS: History of surgical evacuation of the uterus increased
      the risk of surgical evacuation (p = 0.027). Excessive bleeding was not
      associated with any of the studied variables. More misoprostol was needed when
      the duration of gestation exceeded 17+0 weeks (p = 0.036). In multivariate
      analysis the time to fetal expulsion was shorter in women with history of 1-2
      deliveries (hazard ratio [HR] 1.49, 95% confidence interval [CI]; 1.07-2.07), >=3
      deliveries (HR 1.63, 95% CI; 1.11-2.38) and with a two-day interval between
      mifepristone-misoprostol administration (HR 1.71, 95% CI; 1.05-2.81). Patients
      with symptoms (i.e. uterine bleeding or pain) at baseline had longer hospital
      stay (HR 0.66, 95% CI; 0.47-0.92). CONCLUSIONS: The factors affecting the
      outcomes of medical treatment of second-trimester fetal miscarriage are similar
      to those of second-trimester induced abortion. Two-day interval between
      mifepristone-misoprostol administration might decrease the time to fetal
      expulsion and the need of hospital resources.

PMID- 28753655
TI  - Bacterial effector NleL promotes enterohemorrhagic E. coli-induced attaching and
      effacing lesions by ubiquitylating and inactivating JNK.
AB  - As a major diarrheagenic human pathogen, enterohemorrhagic Escherichia coli
      (EHEC) produce attaching and effacing (A/E) lesions, characterized by the
      formation of actin pedestals, on mammalian cells. A bacterial T3SS effector NleL
      from EHEC O157:H7 was recently shown to be a HECT-like E3 ligase in vitro, but
      its biological functions and host targets remain elusive. Here, we report that
      NleL is required to effectively promote EHEC-induced A/E lesions and bacterial
      infection. Furthermore, human c-Jun NH2-terminal kinases (JNKs) were identified
      as primary substrates of NleL. NleL-induced JNK ubiquitylation, particularly mono
      ubiquitylation at the Lys 68 residue of JNK, impairs JNK's interaction with an
      upstream kinase MKK7, thus disrupting JNK phosphorylation and activation. This
      subsequently suppresses the transcriptional activity of activator protein-1 (AP
      1), which modulates the formation of the EHEC-induced actin pedestals. Moreover,
      JNK knockdown or inhibition in host cells complements NleL deficiency in EHEC
      infection. Thus, we demonstrate that the effector protein NleL enhances the
      ability of EHEC to infect host cells by targeting host JNK, and elucidate an
      inhibitory role of ubiquitylation in regulating JNK phosphorylation.

PMID- 28753656
TI  - Simvastatin dose and acute kidney injury without concurrent serious muscle
      injury: A nationwide nested case-control study.
AB  - BACKGROUND: Inconsistent findings from four observational studies suggest that
      the risk of acute kidney injury (AKI) may increase with increasing statin dose or
      potency, but none of the studies took statin-related severe muscle injury,
      including rhabdomyolysis, into account. We undertook a nationwide nested case
      control study in New Zealand to examine the risk of AKI without concurrent
      serious muscle injury according to simvastatin dose in two cohorts: people
      without a history of renal disease and people with non-dialysis dependent chronic
      kidney disease. MATERIALS AND METHODS: A total of 334,710 people aged >= 18 years
      without a history of renal disease (cohort 1) and 5,437 with non-dialysis
      dependent chronic kidney disease (cohort 2) who initiated simvastatin therapy
      between 1 January 2006 and 31 December 2013 were identified using national
      pharmaceutical dispensing and hospital discharge data. Patients who developed AKI
      without concurrent serious muscle injury during follow-up (cases) were
      ascertained using hospital discharge and mortality data (n = 931 from cohort 1, n
      = 160 from cohort 2). Up to 10 controls per case, matched by date of birth, sex,
      and cohort entry date were randomly selected from the relevant cohort using risk
      set sampling. RESULTS: Relative to current use of 20mg simvastatin daily, the
      adjusted odds ratios and 95% confidence intervals (95% CI) in cohort 1 for
      current use of 40mg and 80mg were 0.9 (95% CI 0.7-1.2) and 1.3 (95% CI 0.7-2.3),
      respectively. The adjusted odds ratio for 40mg in cohort 2 was 1.1 (95% CI 0.7
      1.9); the numbers taking 80mg were very small and the confidence interval was
      correspondingly wide. CONCLUSION: The findings of this study suggest that a
      relationship between statin dose and AKI may not exist independent of serious
      muscle injury.

PMID- 28753657
TI  - Evolution of aortic pressure during normal ageing: A model-based study.
AB  - BACKGROUND: The age-related increase in pulse pressure (PP) and systolic blood
      pressure (SBP) is often attributed to alterations in the wave reflection profile
      and augmented contributions of the reflected waves. However, clinical evidence
      shows that the stiffening of the proximal aorta with age and the consequent
      augmentation of the forward pressure wave plays an equally important role. The
      relative importance of the forward and reflected wave components in essential
      hypertension has not yet been fully elucidated. OBJECTIVE: The aim of the current
      investigation was to simulate the major ageing mechanisms in the arterial system
      and the heart using a mathematical one-dimensional model of the arterial tree and
      to assess the evolution of systolic and pulse pressure during normal (non
      pathological) ageing. METHODS AND RESULTS: Our state-of-the-art 1-D model was
      extended to include turbulence and inertial effects of the flow exiting the left
      ventricle. Literature data on the age-associated changes in arterial stiffness,
      peripheral resistance and cardiac contractility were gathered and used as an
      input for the simulations. The predicted evolution of pressure and augmentation
      index with age followed accurately the curves obtained in a number of large-scale
      clinical studies. Analysis of the relative contribution of the forward and
      backward wave components showed that the forward wave becomes the major
      determinant of the increase in central and peripheral SBP and PP with advancing
      age. CONCLUSIONS: The 1-D model of the ageing tree and heart captures faithfully
      and with great accuracy the central pressure evolution with ageing. The
      stiffening of the proximal aorta and the resulting augmentation of the forward
      pressure wave is the major contributor of the systolic pressure augmentation with
      age.

PMID- 28753658
TI  - Neuroanatomy of the spleen: Mapping the relationship between sympathetic neurons
      and lymphocytes.
AB  - The nervous system plays a profound regulatory role in maintaining appropriate
      immune responses by signaling to immune cells. These immune cells, including B-
      and T-cells, can further act as intermediary messengers, with subsets of B- and T
      cells expressing choline acetyltransferase (ChAT), the enzyme required for
      acetylcholine (ACh) synthesis. Neural control of ACh release from ChAT+ T-cells
      can have powerful immune implications, regulating lymphocyte trafficking,
      inflammation, and prevent death due to experimental septic shock. Although ACh
      release from T-cells has been proposed to occur following norepinephrine (NE)
      released from sympathetic nerve terminals in the spleen, it is unknown how this
      communication occurs. While it was proposed that tyrosine hydroxylase (TH+) axons
      form synapse-like structures with ChAT+ T-cells, there is scant evidence to
      support or refute this phenomenon. With this in mind, we sought to determine the
      relative abundance of ChAT+ B- and T-cells in close proximity to TH+ axons, and
      determine what factors contribute to their localization in the spleen. Using
      confocal microscopy of tissue sections and three-dimensional imaging of intact
      spleen, we confirmed that ChAT+ B-cells exceed the number of ChAT+ T-cells, and
      overall few ChAT+ B- or T-cells are located close to TH+ fibers compared to total
      numbers. The organized location of ChAT+ lymphocytes within the spleen suggested
      that these cells were recruited by chemokine gradients. We identified ChAT+ B-
      and T-cells express the chemokine receptor CXCR5; indicating that these cells can
      respond to CXCL13 produced by stromal cells expressing the beta2 adrenergic
      receptor in the spleen. Our findings suggest that sympathetic innervation
      contributes to organization of ChAT+ immune cells in the white pulp of the spleen
      by regulating CXCL13. Supporting this contention, chemical sympathectomy
      significantly reduced expression of this chemokine. Together, we demonstrated
      that there does not appear to be a basis for synaptic neuro-immune communication,
      and that sympathetic innervation can modulate immune function through altering
      stromal cell chemokine production.

PMID- 28753659
TI  - Melanic variation underlies aposematic color variation in two hymenopteran
      mimicry systems.
AB  - The stinging hymenopteran velvet ants (Mutillidae) and bumble bees (Apidae:
      Bombus spp.) have both undergone extensive diversification in aposematic color
      patterns, including yellow-red hues and contrasting dark-light body coloration,
      as a result of Mullerian mimicry. Understanding the genetic and developmental
      mechanisms underlying shifts in these mimetic colors requires characterization of
      their pigmentation. In this study, a combination of solubility,
      spectrophotometry, and melanin degradation analysis are applied to several color
      forms and species of these lineages to determine that orange-red colors in both
      lineages are comprised of primarily dopamine-derived pheomelanins. Until a few
      recent studies, pheomelanins were thought not to occur in insects. These results
      support their potential to occur across insects and particularly among the
      Hymenoptera. Shifts between black and orange-red colors, such as between mimetic
      color forms of bumble bee Bombus melanopygus, are inferred to involve
      modification of the ratios of dark eumelanins to red pheomelanins, thus
      implicating the melanin pathway in mimetic diversification. This discovery
      highlights the need to focus on how pheomelanins are synthesized in the insect
      melanin pathway and the potential for new pigments to be found even in some of
      our most well-known insect systems.

PMID- 28753660
TI  - Molecular systematics of the anchovy genus Encrasicholina in the Northwest
      Pacific.
AB  - The anchovy genus Encrasicholina is an important coastal marine resource of the
      tropical Indo-West Pacific (IWP) region for which insufficient comparative data
      are available to evaluate the effects of current exploitation levels on the
      sustainability of its species and populations. Encrasicholina currently comprises
      nine valid species that are morphologically very similar. Only three,
      Encrasicholina punctifer, E. heteroloba, and E. pseudoheteroloba, occur in the
      Northwest Pacific subregion of the northeastern part of the IWP region. These
      species are otherwise broadly distributed and abundant in the IWP region, making
      them the most important anchovy species for local fisheries. In this study, we
      reconstructed the phylogeny of these three species of Encrasicholina within the
      Engraulidae. We sequenced 10 complete mitochondrial genomes (using high
      throughput and Sanger DNA sequencing technologies) and compared those sequences
      to 21 previously published mitochondrial genomes from various engraulid taxa. The
      phylogenetic results showed that the genus Encrasicholina is monophyletic, and it
      is the sister group to the more-diverse "New World anchovy" clade. The mitogenome
      based dating results indicated that the crown group Encrasicholina originated
      about 33.7 million years ago (nearby the limit Eocene/Oligocene), and each
      species of Encrasicholina has been reproductively isolated from the others for
      more than 20 million years, despite their morphological similarities. In
      contrast, preliminary population genetic analyses across the Northwest Pacific
      region using four mitogenomic sequences revealed very low levels of genetic
      differentiation within Encrasicholina punctifer. These molecular results combined
      with recent taxonomic revisions are important for designing further studies on
      the population structure and phylogeography of these anchovies.

PMID- 28753661
TI  - Amino acid metabolic signaling influences Aedes aegypti midgut microbiome
      variability.
AB  - The mosquito midgut microbiota has been shown to influence vector competence for
      multiple human pathogens. The microbiota is highly variable in the field, and the
      sources of this variability are not well understood, which limits our ability to
      understand or predict its effects on pathogen transmission. In this work, we
      report significant variation in female adult midgut bacterial load between
      strains of A. aegypti which vary in their susceptibility to dengue virus.
      Composition of the midgut microbiome was similar overall between the strains,
      with 81-92% of reads coming from the same five bacterial families, though we did
      detect differences in the presence of some bacterial families including
      Flavobacteriaceae and Entobacteriaceae. We conducted transcriptomic analysis on
      the two mosquito strains that showed the greatest difference in bacterial load,
      and found that they differ in transcript abundance of many genes implicated in
      amino acid metabolism, in particular the branched chain amino acid degradation
      pathway. We then silenced this pathway by targeting multiple genes using RNA
      interference, which resulted in strain-specific bacterial proliferation, thereby
      eliminating the difference in midgut bacterial load between the strains. This
      suggests that the branched chain amino acid (BCAA) degradation pathway controls
      midgut bacterial load, though the mechanism underlying this remains unclear.
      Overall, our results indicate that amino acid metabolism can act to influence the
      midgut microbiota. Moreover, they suggest that genetic or physiological variation
      in BCAA degradation pathway activity may in part explain midgut microbiota
      variation in the field.

PMID- 28753662
TI  - NS3 genomic sequencing and phylogenetic analysis as alternative to a commercially
      available assay to reliably determine hepatitis C virus subtypes 1a and 1b.
AB  - OBJECTIVE: To evaluate the use of hepatitis C virus (HCV) NS3 sequencing as
      alternative to the comercially available Versant HCV 2.0 reverse hybridization
      line-probe assay (LiPA 2.0) to determine HCV genotype 1 (HCV-1) subtypes.
      PATIENTS AND METHODS: A cohort of 104 patients infected by HCV-1 according to
      LiPA 2.0 was analyzed in a cross-sectional study conducted in patients seen from
      January 2012 to June 2016 at an outpatient clinic in Buenos Aires, Argentina.
      RESULTS: The samples were included within well supported subtype clades: 64 with
      HCV-1b and 39 with HCV-1a infection. Twenty of the HCV-1a infected patientes were
      included in a supported sub-clade "1" and 19 individuals were among the basal sub
      clade "2". LiPA 2.0 failed to subtype HCV-1 in 20 (19.2%) individuals. Subtype
      classification determined by NS3 direct sequencing showed that 2/18 (11.1%) of
      the HCV-1a-infected patients as determined by LiPA 2.0 were in fact infected by
      HCV-1b. Of the HCV-1b-infected according to LiPA 2.0, 10/66 (15.2%) patients
      showed HCV-1a infection according to NS3 sequencing. Overall misclassification
      was 14.3% (kappa-index for the concordance with NS3 sequencing = 0.635). One (1%)
      patient was erroneously genotyped as HCV-1 and was revealed as HCV genotype 4
      infection. CONCLUSIONS: Genomic sequencing of the HCV NS3 region represents an
      adequate alternative since it provides reliable genetic information. It even
      distinguishes between HCV-1a clades related to resistance-associated
      substitutions to HCV protease inhibitors, it provides reliable genetic
      information for genotyping/subgenotyping and simultaneously allows to determine
      the presence of resistance-associated substitutions to currently recommended
      DAAs.

PMID- 28753663
TI  - metaSNV: A tool for metagenomic strain level analysis.
AB  - We present metaSNV, a tool for single nucleotide variant (SNV) analysis in
      metagenomic samples, capable of comparing populations of thousands of bacterial
      and archaeal species. The tool uses as input nucleotide sequence alignments to
      reference genomes in standard SAM/BAM format, performs SNV calling for individual
      samples and across the whole data set, and generates various statistics for
      individual species including allele frequencies and nucleotide diversity per
      sample as well as distances and fixation indices across samples. Using published
      data from 676 metagenomic samples of different sites in the oral cavity, we show
      that the results of metaSNV are comparable to those of MIDAS, an alternative
      implementation for metagenomic SNV analysis, while data processing is faster and
      has a smaller storage footprint. Moreover, we implement a set of distance
      measures that allow the comparison of genomic variation across metagenomic
      samples and delineate sample-specific variants to enable the tracking of specific
      strain populations over time. The implementation of metaSNV is available at:
      http://metasnv.embl.de/.

PMID- 28753664
TI  - Validation of a novel Mho microarray for a comprehensive characterisation of the
      Mycoplasma hominis action in HeLa cell infection.
AB  - Mycoplasma hominis is the second smallest facultative pathogen of the human
      urogenital tract. With less than 600 protein-encoding genes, it represents an
      ideal model organism for the study of host-pathogen interactions. For a
      comprehensive characterisation of the M. hominis action in infection a customized
      Mho microarray, which was based on two genome sequences (PG21 and LBD-4), was
      designed to analyze the dynamics of the mycoplasma transcriptome during infection
      and validated for M. hominis strain FBG. RNA preparation was evaluated and
      adapted to ensure the highest recovery of mycoplasmal mRNAs from in vitro HeLa
      cell infection assays. Following cRNA hybridization, the read-out strategy of the
      hybridization results was optimized and confirmed by RT-PCR. A statistically
      robust infection assay with M. hominis strain FBG enabled the identification of
      differentially regulated key effector molecules such as critical cytoadhesins (4
      h post infection (pI)), invasins (48 h pI) and proteins associated with
      establishing chronic infection of the host (336 h pI). Of the 294 differentially
      regulated genes (>2-fold) 128 (43.5%) encoded hypothetical proteins, including
      lipoproteins that seem to play a central role as virulence factors at each stage
      of infection: P75 as a novel cytoadhesin candidate, which is also differentially
      upregulated in chronic infection; the MHO_2100 protein, a postulated invasin and
      the MHO_730-protein, a novel ecto-nuclease and domain of an ABC transporter, the
      function of which in chronic infection has still to be elucidated. Implementation
      of the M. hominis microarray strategy led to a comprehensive identification of to
      date unknown candidates for virulence factors at relevant stages of host cell
      infection.

PMID- 28753665
TI  - Quantification of sympathetic hyperinnervation and denervation after myocardial
      infarction by three-dimensional assessment of the cardiac sympathetic network in
      cleared transparent murine hearts.
AB  - BACKGROUND: The sympathetic nervous system is critical in maintaining the normal
      physiological function of the heart. Its dysfunction in pathological states may
      exacerbate the substrate for arrhythmias. Obviously, knowledge of its three
      dimensional (3D) structure is important, however, it has been revealed by
      conventional methods only to a limited extent. In this study, a new method of
      tissue clearance in combination with immunostaining unravels the 3D structure of
      the sympathetic cardiac network as well as its changes after myocardial
      infarction. METHODS AND RESULTS: Hearts isolated from adult male mice were
      optically cleared using the CUBIC-perfusion protocol. After making the hearts
      transparent, sympathetic nerves and coronary vessels were immunofluorescently
      labeled, and then images were acquired. The spatial distribution of sympathetic
      nerves was visualized not only along the epicardial surface, but also
      transmurally. They were distributed over the epicardial surface and penetrated
      into the myocardium to twist around coronary vessels, but also independent from
      the coronary vasculature. At 2 weeks after myocardial infarction, we were able to
      quantify both denervation distal from the site of infarction and nerve sprouting
      (hyperinnervation) at the ischemic border zone of the hearts in a 3D manner. The
      nerve density at the ischemic border zone was more than doubled in hearts with
      myocardial infarction compared to intact mice hearts (3D analyses; n = 5,
      p<0.05). CONCLUSIONS: There is both sympathetic hyperinnervation and denervation
      after myocardial infarction. Both can be visualized and quantified by a new
      imaging technique in transparent hearts and thereby become a useful tool in
      elucidating the role of the sympathetic nervous system in arrhythmias associated
      with myocardial infarction.

PMID- 28753666
TI  - beta-carbonic anhydrases play a role in salicylic acid perception in Arabidopsis.
AB  - The plant hormone salicylic acid (SA) is required for defense responses. NON
      EXPRESSER OF PATHOGENESIS RELATED 1 (NPR1) and NON RECOGNITION OF BTH-4 (NRB4)
      are required for the response to SA in Arabidopsis (Arabidopsis thaliana). Here,
      we isolated several interactors of NRB4 using yeast two-hybrid assays. Two of
      these interactors, betaCA1 and betaCA2, are beta-carbonic anhydrase family
      proteins. Since double mutant betaca1 betaca2 plants did not show any obvious
      phenotype, we investigated other betaCAs and found that NRB4 also interacts with
      betaCA3 and betaCA4. Moreover, several betaCAs interacted with NPR1 in yeast,
      including one that interacted in a SA-dependent manner. This interaction was
      abolished in loss-of-function alleles of NPR1. Interactions between betaCAs and
      both NRB4 and NPR1 were also detected in planta, with evidence for a triple
      interaction, NRB4-betaCA1-NPR1. The quintuple mutant betaca1 betaca2 betaca3
      betaca4 betaca6 showed partial insensitivity to SA. These findings suggest that
      one of the functions of carbonic anhydrases is to modulate the perception of SA
      in plants.

PMID- 28753667
TI  - Leveraging Twitter to gauge evacuation compliance: Spatiotemporal analysis of
      Hurricane Matthew.
AB  - Hurricane Matthew was the deadliest Atlantic storm since Katrina in 2005 and
      prompted one of the largest recent hurricane evacuations along the Southeastern
      coast of the United States. The storm and its projected landfall triggered a
      massive social media reaction. Using Twitter data, this paper examines the
      spatiotemporal variability in social media response and develops a novel approach
      to leverage geotagged tweets to assess the evacuation responses of residents. The
      approach involves the retrieval of tweets from the Twitter Stream, the creation
      and filtering of different datasets, and the statistical and spatial processing
      and treatment to extract, plot and map the results. As expected, peak Twitter
      response was reached during the pre-impact and preparedness phase, and decreased
      abruptly after the passage of the storm. A comparison between two time periods
      pre-evacuation (October 2th-4th) and post-evacuation (October 7th-9th)-indicates
      that 54% of Twitter users moved away from the coast to a safer location, with
      observed differences by state on the timing of the evacuation. A specific sub
      state analysis of South Carolina illustrated overall compliance with evacuation
      orders and detailed information on the timing of departure from the coast as well
      as the destination location. These findings advance the use of big data and
      citizen-as-sensor approaches for public safety issues, providing an effective and
      near real-time alternative for measuring compliance with evacuation orders.

PMID- 28753668
TI  - Overexpression of Arabidopsis FLOWERING LOCUS T (FT) gene improves floral
      development in cassava (Manihot esculenta, Crantz).
AB  - Cassava is a tropical storage-root crop that serves as a worldwide source of
      staple food for over 800 million people. Flowering is one of the most important
      breeding challenges in cassava because in most lines flowering is late and non
      synchronized, and flower production is sparse. The FLOWERING LOCUS T (FT) gene is
      pivotal for floral induction in all examined angiosperms. The objective of the
      current work was to determine the potential roles of the FT signaling system in
      cassava. The Arabidopsis thaliana FT gene (atFT) was transformed into the cassava
      cultivar 60444 through Agrobacterium-mediated transformation and was found to be
      overexpressed constitutively. FT overexpression hastened flower initiation and
      associated fork-type branching, indicating that cassava has the necessary
      signaling factors to interact with and respond to the atFT gene product. In
      addition, overexpression stimulated lateral branching, increased the prolificacy
      of flower production and extended the longevity of flower development. While FT
      homologs in some plant species stimulate development of vegetative storage
      organs, atFT inhibited storage-root development and decreased root harvest index
      in cassava. These findings collectively contribute to our understanding of flower
      development in cassava and have the potential for applications in breeding.

PMID- 28753669
TI  - Multiscale adaptive analysis of circadian rhythms and intradaily variability:
      Application to actigraphy time series in acute insomnia subjects.
AB  - Circadian rhythms become less dominant and less regular with chronic-degenerative
      disease, such that to accurately assess these pathological conditions it is
      important to quantify not only periodic characteristics but also more irregular
      aspects of the corresponding time series. Novel data-adaptive techniques, such as
      singular spectrum analysis (SSA), allow for the decomposition of experimental
      time series, in a model-free way, into a trend, quasiperiodic components and
      noise fluctuations. We compared SSA with the traditional techniques of cosinor
      analysis and intradaily variability using 1-week continuous actigraphy data in
      young adults with acute insomnia and healthy age-matched controls. The findings
      suggest a small but significant delay in circadian components in the subjects
      with acute insomnia, i.e. a larger acrophase, and alterations in the day-to-day
      variability of acrophase and amplitude. The power of the ultradian components
      follows a fractal 1/f power law for controls, whereas for those with acute
      insomnia this power law breaks down because of an increased variability at the
      90min time scale, reminiscent of Kleitman's basic rest-activity (BRAC) cycles.
      This suggests that for healthy sleepers attention and activity can be sustained
      at whatever time scale required by circumstances, whereas for those with acute
      insomnia this capacity may be impaired and these individuals need to rest or
      switch activities in order to stay focused. Traditional methods of circadian
      rhythm analysis are unable to detect the more subtle effects of day-to-day
      variability and ultradian rhythm fragmentation at the specific 90min time scale.

PMID- 28753670
TI  - Effects of dietary lipids on the hepatopancreas transcriptome of Chinese mitten
      crab (Eriocheir sinensis).
AB  - Fish oil supplies worldwide have declined sharply over the years. To reduce the
      use of fish oil in aquaculture, many studies have explored the effects of fish
      oil substitutions on aquatic animals. To illustrate the effects of dietary lipids
      on Chinese mitten crab and to improve the use of vegetable oils in the diet of
      the crabs, 60 male juvenile Chinese mitten crabs were fed one of five diets for
      116 days: fish oil (FO), soybean oil (SO), linseed oil (LO), FO + SO (1:1, FSO),
      and FO + LO (1:1, FLO). Changes in the crab hepatopancreas transcriptome were
      analyzed using RNA sequencing. There were a total 55,167 unigenes obtained from
      the transcriptome, of which the expression of 3030 was significantly altered in
      the FLO vs. FO groups, but the expression of only 412 unigenes was altered in the
      FSO vs. FO groups. The diets significantly altered the expression of many enzymes
      involved in lipid metabolism, such as pancreatic lipase, long-chain acyl-CoA
      synthetases, carnitine palmitoyltransferase I, acetyl-CoA carboxylase, fatty acid
      synthase, and fatty acyl Delta9-desaturase. The dietary lipids also affected the
      Toll-like receptor and Janus activated kinase-signal transducers and activators
      of transcription signaling pathways. Our results indicate that substituting fish
      oil with vegetable oils in the diet of Chinese mitten crabs might decrease the
      digestion and absorption of dietary lipids, fatty acids biosynthesis, and
      immunologic viral defense, and increase beta-oxidation by altering the expression
      of the relevant genes. Our results lay the foundation for further understanding
      of lipid nutrition in Chinese mitten crab.

PMID- 28753671
TI  - Self-reported infections during international travel and notifiable infections
      among returning international travellers, Sweden, 2009-2013.
AB  - We studied food and water-borne diseases (FWDs), sexually transmitted diseases
      (STDs), vector-borne diseases (VBDs) and diseases vaccinated against in the
      Swedish childhood vaccination programme among Swedish international travellers,
      in order to identify countries associated with a high number of infections. We
      used the national database for notifiable infections to estimate the number of
      FWDs (campylobacteriosis, salmonellosis, giardiasis, shigellosis, EHEC, Entamoeba
      histolytica, yersinosis, hepatitis A, paratyphoid fever, typhoid fever, hepatitis
      E, listeriosis, cholera), STIs (chlamydia, gonorrhoea and acute hepatitis B),
      VBDs (dengue fever, malaria, West Nile fever, Japanese encephalitis and yellow
      fever) and diseases vaccinated against in the Swedish childhood vaccination
      programme (pertussis, measles, mumps, rubella, diphtheria) acquired abroad 2009
      2013. We obtained number and duration of trips to each country from a database
      that monthly collects travel data from a randomly selected proportion of the
      Swedish population. We calculated number of infections per country 2009-2013 and
      incidence/million travel days for the five countries with the highest number of
      infections. Thailand had the highest number of FWDs (7,697, incidence 191/million
      travel days), STIs (1,388, incidence 34/million travel days) and VBDs (358,
      incidence 9/million travel days). France had the highest number of cases of
      diseases vaccinated against in the Swedish childhood vaccination programme (8,
      0.4/million travel days). Swedish travellers contracted most infections in
      Thailand. Special focus should be placed on giving advice to travellers to this
      destination.

PMID- 28753672
TI  - An increase in immature beta-cells lacking Glut2 precedes the expansion of beta
      cell mass in the pregnant mouse.
AB  - A compensatory increase in beta-cell mass occurs during pregnancy to counter the
      associated insulin resistance, and a failure in adaptation is thought to
      contribute to gestational diabetes. Insulin-expressing but glucose-transporter-2
      low (Ins+Glut2LO) progenitor cells are present in mouse and human pancreas, being
      predominantly located in extra-islet beta-cell clusters, and contribute to the
      regeneration of the endocrine pancreas following induced ablation. We therefore
      sought to investigate the contribution of Ins+Glut2LO cells to beta-cell mass
      expansion during pregnancy. Female C57Bl/6 mice were time mated and pancreata
      were collected at gestational days (GD) 6, 9, 12, 15, and 18, and postpartum D7
      (n = 4/time-point) and compared to control (non-pregnant) animals. Beta cell
      mass, location, proliferation (Ki67+), and proportion of Ins+Glut2LO cells were
      measured using immunohistochemistry and bright field or confocal microscopy. Beta
      cell mass tripled by GD18 and beta-cell proliferation peaked at GD12 in islets
      (>=6 beta-cells) and small beta-cell clusters (1-5 beta-cells). The proportion
      and fraction of Ins+Glut2LO cells undergoing proliferation increased
      significantly at GD9 in both islets and clusters, preceding the increase in beta
      cell mass and proliferation, and their proliferation within clusters persisted
      until GD15. The overall number of clusters increased significantly at GD9.
      Quantitative PCR showed a significant increase in Pdx1 presence at GD9 vs. GD18
      or control pancreas, and Pdx1 was visualized by immunohistochemistry within both
      Ins+Glut2LO and Ins+Glut2HI cells within clusters. These results indicate that
      Ins+Glut2LO cells are likely to contribute to beta-cell mass expansion during
      pregnancy.

PMID- 28753673
TI  - Rhizosphere hydrophobicity: A positive trait in the competition for water.
AB  - The ability to acquire water from the soil is a major driver in interspecific
      plant competition and it depends on several root functional traits. One of these
      traits is the excretion of gel-like compounds (mucilage) that modify physical
      soil properties. Mucilage secreted by roots becomes hydrophobic upon drying,
      impedes the rewetting of the soil close to the root, the so called rhizosphere,
      and reduces water availability to plants. The function of rhizosphere
      hydrophobicity is not easily understandable when looking at a single plant, but
      it may constitute a competitive advantage at the ecosystem level. We hypothesize
      that by making the top soil hydrophobic, deep-rooted plants avoid competititon
      with shallow-rooted plants. To test this hypothesis we used an individual-based
      model to simulate water uptake and growth of two virtual plant species, one deep
      rooted plant capable of making the soil hydrophobic and a shallow-rooted plant.
      We ran scenarios with different precipitation regimes ranging from dry to wet
      (350, 700, and 1400 mm total annual precipitation) and from high to low
      precipitation frequencies (1, 7, and 14 days). Plant species abundance and
      biomass were chosen as indicators for competitiveness of plant species. At
      constant precipitation frequency mucilage hydrophobicity lead to a benefit in
      biomass and abundance of the tap-rooted population. Under wet conditions this
      effect diminished and tap-rooted plants were less productive. Without this trait
      both species coexisted. The effect of root exudation trait remained constant
      under different precipitation frequencies. This study shows that mucilage
      secretion is a competitive trait for the acquisition of water. This advantage is
      achieved by the modification of the soil hydraulic properties and specifically by
      inducing water repellency in soil regions which are shared with other species.

PMID- 28753674
TI  - Optimizing the maximum reported cluster size in the spatial scan statistic for
      ordinal data.
AB  - The spatial scan statistic is an important tool for spatial cluster detection.
      There have been numerous studies on scanning window shapes. However, little
      research has been done on the maximum scanning window size or maximum reported
      cluster size. Recently, Han et al. proposed to use the Gini coefficient to
      optimize the maximum reported cluster size. However, the method has been
      developed and evaluated only for the Poisson model. We adopt the Gini coefficient
      to be applicable to the spatial scan statistic for ordinal data to determine the
      optimal maximum reported cluster size. Through a simulation study and application
      to a real data example, we evaluate the performance of the proposed approach.
      With some sophisticated modification, the Gini coefficient can be effectively
      employed for the ordinal model. The Gini coefficient most often picked the
      optimal maximum reported cluster sizes that were the same as or smaller than the
      true cluster sizes with very high accuracy. It seems that we can obtain a more
      refined collection of clusters by using the Gini coefficient. The Gini
      coefficient developed specifically for the ordinal model can be useful for
      optimizing the maximum reported cluster size for ordinal data and helpful for
      properly and informatively discovering cluster patterns.

PMID- 28753675
TI  - Can home care for homebound patients with chronic heart failure reduce
      hospitalizations and costs?
AB  - BACKGROUND: Congestive heart failure (CHF), a common problem in adults, is
      associated with multiple hospitalizations, high mortality rates and high costs.
      PURPOSE: To evaluate whether home care for homebound patients with CHF reduces
      healthcare service utilization and overall costs. METHODS: A retrospective study
      of healthcare utilization among homebound patients who received home care for CHF
      from 2012-1015. The outcome measures were number of hospital admissions per
      month, total number of hospitalization days and days for CHF only, emergency room
      visits, and overall costs. A comparison was conducted between the 6-month period
      prior to entry into home care and the time in home care. RESULTS: Over the study
      period 196 patients were treated by home care for CHF with a mean age of 79.4+/
      9.5 years. 113 (57.7%) were women. Compared to the six months prior to home care,
      there were statistically significant decreases in hospitalizations (46.3%), in
      the number of total in-hospital days (28.7%), in the number of in-hospital days
      for CHF (66.7%), in emergency room visits (47%), and in overall costs (23.9%).
      CONCLUSION: Home care for homebound adults with CHF can reduce healthcare
      utilization and healthcare costs.

PMID- 28753676
TI  - Intraday seasonalities and nonstationarity of trading volume in financial
      markets: Collective features.
AB  - Employing Random Matrix Theory and Principal Component Analysis techniques, we
      enlarge our work on the individual and cross-sectional intraday statistical
      properties of trading volume in financial markets to the study of collective
      intraday features of that financial observable. Our data consist of the trading
      volume of the Dow Jones Industrial Average Index components spanning the years
      between 2003 and 2014. Computing the intraday time dependent correlation matrices
      and their spectrum of eigenvalues, we show there is a mode ruling the collective
      behaviour of the trading volume of these stocks whereas the remaining eigenvalues
      are within the bounds established by random matrix theory, except the second
      largest eigenvalue which is robustly above the upper bound limit at the opening
      and slightly above it during the morning-afternoon transition. Taking into
      account that for price fluctuations it was reported the existence of at least
      seven significant eigenvalues-and that its autocorrelation function is close to
      white noise for highly liquid stocks whereas for the trading volume it lasts
      significantly for more than 2 hours -, our finding goes against any expectation
      based on those features, even when we take into account the Epps effect. In
      addition, the weight of the trading volume collective mode is intraday dependent;
      its value increases as the trading session advances with its eigenversor
      approaching the uniform vector as well, which corresponds to a soar in the
      behavioural homogeneity. With respect to the nonstationarity of the collective
      features of the trading volume we observe that after the financial crisis of 2008
      the coherence function shows the emergence of an upset profile with large
      fluctuations from that year on, a property that concurs with the modification of
      the average trading volume profile we noted in our previous individual analysis.

PMID- 28753677
TI  - Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in
      ovarian cancer.
AB  - Pyruvate kinase M2 (PKM2) regulates glycolysis and oxidative phosphorylation;
      however, the role of PKM2 in ovarian cancer remains largely unknown. We
      investigated whether ovarian cancer metabolism could provide insight into the
      development of therapeutic strategies. We performed immunohistochemical staining
      for PKM2 on a tissue microarray for multivariate analysis. It revealed that
      patients exhibiting higher PKM2 expression were significantly associated with
      malignancy groups (p < 0.001) and pathogenesis models (p < 0.001), had poor
      progression-free survival rates (p = 0.01) as compared with patients exhibiting
      lower PKM2 levels, and yielded a hazard ratio of death of 2.02 (95% confidence
      interval: 0.70-5.85). In cell lines, PKM2 inhibitor significantly inhibited the
      glycolytic rate according to cellular glucose consumption (p < 0.001). We also
      utilized Seahorse assays to assess metabolism-related cell-specific factors and
      the impact of PKM2 inhibitors. Energy shifts as per Seahorse analysis showed
      attenuation of the extracellular acidification rate (p < 0.05) and no significant
      difference in oxygen-consumption rate in SKOV3 cells. Treatment with PKM2
      inhibitor suppressed ovarian cancer growth and cell migration in vitro and
      inhibited tumor growth without significant toxicity in a xenograft study. PKM2
      inhibition disturbed Warburg effects and inhibited ovarian cancer cell growth.
      Targeting PKM2 may constitute a promising therapy for patients with ovarian
      cancer, and clinical trials involving shikonin are warranted.

PMID- 28753678
TI  - Coughing, sneezing, and aching online: Twitter and the volume of influenza-like
      illness in a pediatric hospital.
AB  - This study investigates the relation of the incidence of georeferenced tweets
      related to respiratory illness to the incidence of influenza-like illness (ILI)
      in the emergency department (ED) and urgent care clinics (UCCs) of a large
      pediatric hospital. We collected (1) tweets in English originating in our
      hospital's primary service area between 11/1/2014 and 5/1/2015 and containing one
      or more specific terms related to respiratory illness and (2) the daily number of
      patients presenting to our hospital's EDs and UCCs with ILI, as captured by ICD-9
      codes. A Support Vector Machine classifier was applied to the set of tweets to
      remove those unlikely to be related to ILI. Time series of the pooled set of
      remaining tweets involving any term, of tweets involving individual terms, and of
      the ICD-9 data were constructed, and temporal cross-correlation between the
      social media and clinical data was computed. A statistically significant
      correlation (Spearman rho = 0.23) between tweets involving the term flu and ED
      and UCC volume related to ILI 11 days in the future was observed. Tweets
      involving the terms coughing (Spearman rho = 0.24) and headache (Spearman rho =
      0.19) individually were also significantly correlated to ILI-related clinical
      volume four and two days in the future, respectively. In the 2014-2015 cold and
      flu season, the incidence of local tweets containing the terms flu, coughing, and
      headache were early indicators of the incidence of ILI-related cases presenting
      to EDs and UCCs at our children's hospital.

PMID- 28753679
TI  - The bias of experimental design, including strain background, in the
      determination of critical Streptococcus suis serotype 2 virulence factors.
AB  - Streptococcus suis serotype 2 is an important porcine bacterial pathogen and
      emerging zoonotic agent mainly responsible for sudden death, septic shock, and
      meningitis. However, serotype 2 strains are genotypically and phenotypically
      heterogeneous. Though a multitude of virulence factors have been described for S.
      suis serotype 2, the lack of a clear definition regarding which ones are truly
      "critical" has created inconsistencies that have only recently been highlighted.
      Herein, the involvement of two factors previously described as being critical for
      S. suis serotype 2 virulence, whether the dipeptidyl peptidase IV and autolysin,
      were evaluated with regards to different ascribed functions using prototype
      strains belonging to important sequence types. Results demonstrate a lack of
      reproducibility with previously published data. In fact, the role of the
      dipeptidyl peptidase IV and autolysin as critical virulence factors could not be
      confirmed. Though certain in vitro functions may be ascribed to these factors,
      their roles are not unique for S. suis, probably due to compensation by other
      factors. As such, variations and discrepancies in experimental design, including
      in vitro assays, cell lines, and animal models, are an important source of
      differences between results. Moreover, the use of different sequence types in
      this study demonstrates that the role attributed to a virulence factor may vary
      according to the S. suis serotype 2 strain background. Consequently, it is
      necessary to establish standard experimental designs according to the experiment
      and purpose in order to facilitate comparison between laboratories. Alongside,
      studies should include strains of diverse origins in order to prevent erroneous
      and biased conclusions that could affect future studies.

PMID- 28753680
TI  - Increasing prevalence of overweight and obesity in Bangladeshi women of
      reproductive age: Findings from 2004 to 2014.
AB  - BACKGROUND: Overweight and obesity are a particular concern for women of
      reproductive age. They not only increase the risk of chronic diseases but they
      are also associated with adverse perinatal, neonatal, infant and child outcomes.
      The objective of this study was to examine the trend of overweight and obesity
      among Bangladeshi women of reproductive age between 2004 and 2014. METHOD: This
      is a secondary data analysis of the 2004, 2007, 2011 and 2014 Bangladesh
      Demographic and Health Surveys (BDHS). We determined the age standardized
      prevalence of overweight and obesity of women aged 15-49 years, who had their
      weight and height measured. Overweight and obesity were determined using the
      Asian specific BMI cut-offs criteria. RESULT: The prevalence of overweight
      increased from 11.4% [95% CI: 10.4to 12.5] in 2004 to 25.2% [95% CI: 24.0 to
      26.4] in 2014. The prevalence of obesity increased from 3.5% [95% CI: 3.0to4.2]
      to 11.2% [95% CI: 10.1to12.5%] over the same period of time. This was seen in all
      age groups. However, the greatest increase was observed in women aged 35 to 49
      years. The highest prevalence of overweight and obesity were observed in those
      women with the highest education level and wealth, larger family size, living in
      urban areas and not being in paid employment. CONCLUSION: The prevalence of
      overweight and obesity among women of reproductive age in Bangladesh is high and
      increasing. We speculate that this has the potential to jeopardize the
      improvements that have been made in maternal and infant health over the last two
      decades. Evidence based prevention strategies are required to address this
      serious public health issue.

PMID- 28753681
TI  - Correction: Hypothalamic over-expression of VGF in the Siberian hamster increases
      energy expenditure and reduces body weight gain.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0172724.].

PMID- 28753682
TI  - A new computational strategy for identifying essential proteins based on network
      topological properties and biological information.
AB  - Essential proteins are the proteins that are indispensable to the survival and
      development of an organism. Deleting a single essential protein will cause
      lethality or infertility. Identifying and analysing essential proteins are key to
      understanding the molecular mechanisms of living cells. There are two types of
      methods for predicting essential proteins: experimental methods, which require
      considerable time and resources, and computational methods, which overcome the
      shortcomings of experimental methods. However, the prediction accuracy of
      computational methods for essential proteins requires further improvement. In
      this paper, we propose a new computational strategy named CoTB for identifying
      essential proteins based on a combination of topological properties, subcellular
      localization information and orthologous protein information. First, we introduce
      several topological properties of the protein-protein interaction (PPI) network.
      Second, we propose new methods for measuring orthologous information and
      subcellular localization and a new computational strategy that uses a random
      forest prediction model to obtain a probability score for the proteins being
      essential. Finally, we conduct experiments on four different Saccharomyces
      cerevisiae datasets. The experimental results demonstrate that our strategy for
      identifying essential proteins outperforms traditional computational methods and
      the most recently developed method, SON. In particular, our strategy improves the
      prediction accuracy to 89, 78, 79, and 85 percent on the YDIP, YMIPS, YMBD and
      YHQ datasets at the top 100 level, respectively.

PMID- 28753683
TI  - Parenteral Na2S, a fast-releasing H2S donor, but not GYY4137, a slow-releasing
      H2S donor, lowers blood pressure in rats.
AB  - Hydrogen sulfide (H2S) is involved in blood pressure regulation. We evaluated
      hemodynamic effects of Na2S and morpholin-4-ium (4
      methoxyphenyl)(morpholino)phosphinodithioate (GYY4137), H2S donors. GYY4137 is
      the most widely studied slow-releasing H2S donor, however, its ability to release
      H2S under physiological conditions is unclear. Hemodynamics were recorded in
      anaesthetized Wistar-Kyoto rats at baseline and after intravenous (IV) or
      intraperitoneal (IP) administration of either a vehicle (20% dimethyl sulfoxide),
      GYY4137 or Na2S. The stability of GYY4137 in buffers and in plasma was evaluated
      with nuclear magnetic resonance. The vehicle, as well as GYY4137, given IV did
      not affect mean arterial blood pressure (MABP), whereas Na2S produced a
      significant decrease in MABP. Similarly, IP given Na2S, but not GYY4137, lowered
      MABP. In the buffers at pH of 7.4 and 5.5 and in rat plasma no reaction of
      GYY4137 was found during 18 hours of observation. In contrast, rapid
      decomposition of GYY4137 occurred in buffers at pH 2.0. In conclusion, parenteral
      GYY4137 does not exert a hemodynamic effect in Wistar-Kyoto rats. This seems to
      be due to the high stability of GYY4137 at physiological pH. Therefore, it is
      likely that widely reported biological effects of GYY4137 are not H2S-dependent
      but may depend on GYY4137 itself. However, the H2S-dependent biological effects
      of GYY4137 may be expected in tissues characterized by low pH.

PMID- 28753684
TI  - ERRATUM: Unexpected Serious Cardiac Arrhythmias in the Setting of Loperamide
      Abuse.
AB  - Loperamide (Imodium) is a non-prescription opioid receptor agonist available over
      the-counter for the treatment of diarrhea. When ingested in excessive doses,
      loperamide can penetrate the blood-brain barrier and is reported to produce
      euphoria, central nervous system and respiratory depression, and cardiotoxicity.
      There is an emerging trend in its use among drug abusers for its euphoric effects
      or for self-treatment of opioid withdrawal. We report a case of ventricular
      dysrhythmias associated with loperamide abuse in a 28-year-old man who
      substituted loperamide for the opioids that he used to abuse. [Full article
      available at http://rimed.org/rimedicaljournal-2017-04.asp, free with no login].

PMID- 28753685
TI  - Effects of Lumbar Spine Assemblies and Body-Borne Equipment Mass on
      Anthropomorphic Test Device Responses During Drop Tests.
AB  - When simulating or conducting land mine blast tests on armored vehicles to assess
      potential occupant injury, the preference is to use the Hybrid III
      anthropomorphic test device (ATD). In land blast events, neither the effect of
      body-borne equipment (BBE) on the ATD response nor the dynamic response index
      (DRI) is well understood. An experimental study was carried out using a drop
      tower test rig, with a rigid seat mounted on a carriage table undergoing average
      accelerations of 161 g and 232 g over 3 ms. A key aspect of the work looked at
      the various lumbar spine assemblies available for a Hybrid III ATD. These can
      result in different load cell orientations for the ATD which in turn can affect
      the load measurement in the vertical and horizontal planes. Thirty-two tests were
      carried out using two BBE mass conditions and three variations of ATDs. The
      latter were the Hybrid III with the curved (conventional) spine, the Hybrid III
      with the pedestrian (straight) spine, and the Federal Aviation Administration
      (FAA) Hybrid III which also has a straight spine. The results showed that the
      straight lumbar spine assemblies produced similar ATD responses in drop tower
      tests using a rigid seat. In contrast, the curved lumbar spine assembly generated
      a lower pelvis acceleration and a higher lumbar load than the straight lumbar
      spine assemblies. The maximum relative displacement of the lumbar spine occurred
      after the peak loading event, suggesting that the DRI is not suitable for
      assessing injury when the impact duration is short and an ATD is seated on a
      rigid seat on a drop tower. The peak vertical lumbar loads did not change with
      increasing BBE mass because the equipment mass effects did not become a factor
      during the peak loading event.

PMID- 28753686
TI  - Understanding individual differences in color appearance of "#TheDress" based on
      the optimal color hypothesis.
AB  - We performed a theoretical analysis based on our optimal color hypothesis to
      explain why "#TheDress" image had a different color appearance for different
      observers (observer-dependent perception). We then carried out an experiment to
      test the hypothesis derived from the aforementioned theoretical analysis. In the
      optimal color hypothesis, the visual system picks the optimal color distribution
      that provides the best fit to the luminance distribution at a scene. The peak of
      the best-fit optimal color distribution corresponds with the illuminant's color
      temperature. In the theoretical analysis, we found that as the luminance level
      was increased the best-fit optimal color temperature changes abruptly from high
      to low at a specific luminance-level. Under the dark-blue (low luminance and high
      color temperature) illuminant the dress should appear white/gold whereas under
      the bright-white (high luminance and low color temperature) illuminant the dress
      should appear blue/black. The observer-dependent appearances of the dress may be
      explained by this luminance-dependent illuminant prediction. In the experiment,
      we used the original dress, a chromatically inverted dress, and an achromatic
      dress as stimuli. The observer adjusted chromaticity and luminance of a test
      field drawn onto the dress image so that it appeared as a full-white surface. We
      found that the white/gold group estimated the illuminant to be darker and bluish
      and the blue/black group estimated it to be brighter and yellowish. The
      observer's estimated illuminant was consistent with the predicted illuminant by
      the optimal color theory. It was newly discovered that even when the dress was
      achromatic, these two groups estimated the illuminant to be darker or brighter in
      the same way as for the original dress.

PMID- 28753687
TI  - Strain-Level Dependent Nonequilibrium Anisotropic Viscoelasticity: Application to
      the Abdominal Muscle.
AB  - Soft connective tissues sustain large strains of viscoelastic nature. The rate
      independent component is frequently modeled by means of anisotropic hyperelastic
      models. The rate-dependent component is usually modeled through linear
      rheological models or quasi-linear viscoelastic (QLV) models. These viscoelastic
      models are unable, in general, to capture the strain-level dependency of the
      viscoelastic properties present in many viscoelastic tissues. In linear
      viscoelastic models, strain-level dependency is frequently accounted for by
      including the dependence of multipliers of Prony series on strains through
      additional evolution laws, but the determination of the material parameters is a
      difficult task and the obtained accuracy is usually not sufficient. In this work,
      we introduce a model for fully nonlinear viscoelasticity in which the
      instantaneous and quasi-static behaviors are exactly captured and the relaxation
      curves are predicted to a high accuracy. The model is based on a fully nonlinear
      standard rheological model and does not necessitate optimization algorithms to
      obtain material parameters. Furthermore, in contrast to most models used in
      modeling the viscoelastic behavior of soft tissues, it is valid for the large
      deviations from thermodynamic equilibrium typically observed in soft tissues.

PMID- 28753688
TI  - The Role of Neck Muscle Activities on the Risk of Mild Traumatic Brain Injury in
      American Football.
AB  - Concussion, or mild traumatic brain injury (mTBI), is frequently associated with
      sports activities. It has generally been accepted that neck strengthening
      exercises are effective as a preventive strategy for reducing sports-related
      concussion risks. However, the interpretation of the link between neck strength
      and concussion risks remains unclear. In this study, a typical helmeted head-to
      head impact in American football was simulated using the head and neck complex
      finite element (FE) model. The impact scenario selected was previously reported
      in lab-controlled incident reconstructions from high-speed video footages of the
      National Football League using two head-neck complexes taken from Hybrid III
      dummies. Four different muscle activation strategies were designed to represent
      no muscle response, a reactive muscle response, a pre-activation response, and
      response due to stronger muscle strength. Head kinematics and various head/brain
      injury risk predictors were selected as response variables to compare the effects
      of neck muscles on the risk of sustaining the concussion. Simulation results
      indicated that active responses of neck muscles could effectively reduce the risk
      of brain injury. Also, anticipatory muscle activation played a dominant role on
      impact outcomes. Increased neck strength can decrease the time to compress the
      neck and its effects on reducing brain injury risks need to be further studied.

PMID- 28753689
TI  - Variable Thumb Moment Arm Modeling and Thumb-Tip Force Production of a Human-Like
      Robotic Hand.
AB  - The anatomically correct testbed (ACT) hand mechanically simulates the
      musculoskeletal structure of the fingers and thumb of the human hand. In this
      work, we analyze the muscle moment arms (MAs) and thumb-tip force vectors in the
      ACT thumb in order to compare the ACT thumb's mechanical structure to the human
      thumb. Motion data are used to determine joint angle-dependent MA models, and
      thumb-tip three-dimensional (3D) force vectors are experimentally analyzed when
      forces are applied to individual muscles. Results are presented for both a
      nominal ACT thumb model designed to match human MAs and an adjusted model that
      more closely replicates human-like thumb-tip forces. The results confirm that the
      ACT thumb is capable of faithfully representing human musculoskeletal structure
      and muscle functionality. Using the ACT hand as a physical simulation platform
      allows us to gain a better understanding of the underlying biomechanical and
      neuromuscular properties of the human hand to ultimately inform the design and
      control of robotic and prosthetic hands.

PMID- 28753690
TI  - Thermal Analyses of a Human Kidney and a Rabbit Kidney During Cryopreservation by
      Vitrification.
AB  - This study focuses on thermal analysis of the problem of scaling up from the
      vitrification of rabbit kidneys to the vitrification of human kidneys, where
      vitrification is the preservation of biological material in the glassy state. The
      basis for this study is a successful cryopreservation protocol for a rabbit
      kidney model, based on using a proprietary vitrification solution known as M22.
      Using the finite element analysis (FEA) commercial code ANSYS, heat transfer
      simulations suggest that indeed the rabbit kidney unquestionably cools rapidly
      enough to be vitrified based on known intrarenal concentrations of M22. Scaling
      up 21-fold, computer simulations suggest less favorable conditions for human
      kidney vitrification. In this case, cooling rates below -100  degrees C are
      sometimes slower than 1  degrees C/min, a rate that provides a clear-cut margin
      of safety at all temperatures based on the stability of rabbit kidneys in past
      studies. Nevertheless, it is concluded in this study that vitrifying human
      kidneys is possible without significant ice damage, assuming that human kidneys
      can be perfused with M22 as effectively as rabbit kidneys. The thermal analysis
      suggests that cooling rates can be further increased by a careful design of the
      cryogenic protocol and by tailoring the container to the shape of the kidney, in
      contrast to the present cylindrical container. This study demonstrates the
      critical need for the thermal analysis of experimental cryopreservation and
      highlights the unmet need for measuring the thermophysical properties of
      cryoprotective solutions under conditions relevant to realistic thermal
      histories.

PMID- 28753691
TI  - Experimental Study of Anisotropic Stress/Strain Relationships of Aortic and
      Pulmonary Artery Homografts and Synthetic Vascular Grafts.
AB  - Homografts and synthetic grafts are used in surgery for congenital heart disease
      (CHD). Determining these materials' mechanical properties will aid in
      understanding tissue behavior when subjected to abnormal CHD hemodynamics.
      Homograft tissue samples from anterior/posterior aspects, of ascending/descending
      aorta (AA, DA), innominate artery (IA), left subclavian artery (LScA), left
      common carotid artery (LCCA), main/left/right pulmonary artery (MPA, LPA, RPA),
      and synthetic vascular grafts, were obtained in three orientations:
      circumferential, diagonal (45 deg relative to circumferential direction), and
      longitudinal. Samples were subjected to uniaxial tensile testing (UTT). True
      strain-Cauchy stress curves were individually fitted for each orientation to
      calibrate Fung model. Then, they were used to calibrate anisotropic Holzapfel
      Gasser model (R2 > 0.95). Most samples demonstrated a nonlinear hyperelastic
      strain-stress response to UTT. Stiffness (measured by tangent modulus at
      different strains) in all orientations were compared and shown as contour plots.
      For each vessel segment at all strain levels, stiffness was not significantly
      different among aspects and orientations. For synthetic grafts, stiffness was
      significantly different among orientations (p < 0.042). Aorta is significantly
      stiffer than pulmonary artery at 10% strain, comparing all orientations, aspects,
      and regions (p = 0.0001). Synthetic grafts are significantly stiffer than aortic
      and pulmonary homografts at all strain levels (p < 0.046). Aortic, pulmonary
      artery, and synthetic grafts exhibit hyperelastic biomechanical behavior with
      anisotropic effect. Differences in mechanical properties among vascular grafts
      may affect native tissue behavior and ventricular/arterial mechanical coupling,
      and increase the risk of deformation due to abnormal CHD hemodynamics.

PMID- 28753692
TI  - Modal Damping Ratio and Optimal Elastic Moduli of Human Body Segments for
      Anthropometric Vibratory Model of Standing Subjects.
AB  - The present study aims to accurately estimate inertial, physical, and dynamic
      parameters of human body vibratory model consistent with physical structure of
      the human body that also replicates its dynamic response. A 13 degree-of-freedom
      (DOF) lumped parameter model for standing person subjected to support excitation
      is established. Model parameters are determined from anthropometric measurements,
      uniform mass density, elastic modulus of individual body segments, and modal
      damping ratios. Elastic moduli of ellipsoidal body segments are initially
      estimated by comparing stiffness of spring elements, calculated from a detailed
      scheme, and values available in literature for same. These values are further
      optimized by minimizing difference between theoretically calculated platform-to
      head transmissibility ratio (TR) and experimental measurements. Modal damping
      ratios are estimated from experimental transmissibility response using two
      dominant peaks in the frequency range of 0-25 Hz. From comparison between dynamic
      response determined form modal analysis and experimental results, a set of
      elastic moduli for different segments of human body and a novel scheme to
      determine modal damping ratios from TR plots, are established. Acceptable match
      between transmissibility values calculated from the vibratory model and
      experimental measurements for 50th percentile U.S. male, except at very low
      frequencies, establishes the human body model developed. Also, reasonable
      agreement obtained between theoretical response curve and experimental response
      envelop for average Indian male, affirms the technique used for constructing
      vibratory model of a standing person. Present work attempts to develop effective
      technique for constructing subject specific damped vibratory model based on its
      physical measurements.

PMID- 28753693
TI  - In vivo characterization of structural changes after topical application of
      glucocorticoids in healthy human skin.
AB  - Topical glucocorticoids (GC) are known to induce changes in human skin with the
      potential to develop skin atrophy. Here, atrophogenic effects and subsequent
      structural changes in the skin after topical application of GC were investigated
      in vivo. Sixteen healthy volunteers were topically treated daily on the forearms
      with clobetasol propionate, betamethasone dipropionate, and the petrolatum
      vehicle for 4 weeks. All treated skin areas and a nontreated control area were
      examined by ultrasound, optical coherence tomography, confocal laser scanning
      microscopy, multiphoton tomography (MPT), and resonance Raman spectroscopy at
      baseline 1 day after last application and 1 week after last application.
      Investigated parameters included stratum corneum thickness, epidermal, and full
      skin thickness, keratinocyte size and density, keratinocyte nucleus-to-cytoplasm
      ratio, skin surface classification, relative collagen and elastin signal
      intensity, second-harmonic generation-to-autofluorescence aging index of dermis
      (SAAID), and the antioxidant status of the skin. A reduction in epidermal and
      dermal skin thickness was observed in GC treated as well as in vehicle-treated
      and untreated skin areas on the volar forearm. MPT analysis showed an increased
      epidermal cell density and reduced cell size and nucleus-to-cytoplasm ratio and a
      significant increase of SAAID after GC treatment indicating a restructuring or
      compression of collagen fibers clinically being observed as atrophic changes.

PMID- 28753694
TI  - Endogenous Sheet-Averaged Tension Within a Large Epithelial Cell Colony.
AB  - Epithelial cells form quasi-two-dimensional sheets that function as contractile
      media to effect tissue shape changes during development and homeostasis.
      Endogenously generated intrasheet tension is a driver of such changes, but has
      predominantly been measured in the presence of directional migration. The nature
      of epithelial cell-generated forces transmitted over supracellular distances, in
      the absence of directional migration, is thus largely unclear. In this report, we
      consider large epithelial cell colonies which are archetypical multicell
      collectives with extensive cell-cell contacts but with a symmetric (circular)
      boundary. Using the traction force imbalance method (TFIM) (traction force
      microscopy combined with physical force balance), we first show that one can
      determine the colony-level endogenous sheet forces exerted at the midline by one
      half of the colony on the other half with no prior assumptions on the uniformity
      of the mechanical properties of the cell sheet. Importantly, we find that this
      colony-level sheet force exhibits large variations with orientation-the
      difference between the maximum and minimum sheet force is comparable to the
      average sheet force itself. Furthermore, the sheet force at the colony midline is
      largely tensile but the shear component exhibits significantly more variation
      with orientation. We thus show that even an unperturbed epithelial colony with a
      symmetric boundary shows significant directional variation in the endogenous
      sheet tension and shear forces that subsist at the colony level.

PMID- 28753695
TI  - Usefulness of a newly designed plastic stent for endoscopic re-intervention in
      patients with malignant hilar biliary obstruction.
AB  - Background and study aims We designed a new 7-Fr plastic stent for treating self
      expandable metal stent (SEMS) obstruction in patients with malignant hilar
      biliary obstruction (MHBO) via endoscopic re-intervention with the stent-in-stent
      (SIS) method and evaluated its efficacy. Patients and methods A total of 33
      consecutive patients who underwent endoscopic re-intervention for metal stent
      obstruction after multi-branched SEMS placement were enrolled. The initial SEMSs
      were placed in two or three biliary branches in 14 and 19 patients, respectively.
      We retrospectively evaluated the technical and clinical success, and adverse
      events. Technical success was defined as successful plastic stent placement into
      all target branches through the lumen of the SEMS. Results The technical success
      rates were 85.7 % (12/14) and 78.9 % (15/19) in patients who underwent two- or
      three-branched biliary drainage, respectively. The clinical success rate was 100
      % in the 27 patients in whom technical success was achieved. We achieved
      successful plastic stent placement in more than two branches, using the new
      plastic stent combined with a conventional plastic stent, in 97.0 % (32/33).
      Conclusions This new plastic stent was technically feasible for treating stent
      obstruction via re-intervention with SIS methods.

PMID- 28753696
TI  - Colorectal endoscopic full-thickness resection using a novel, flat-base over-the
      scope clip: a prospective study.
AB  - : Background and study aims We aimed to evaluate the feasibility and safety of a
      new, flat-based over-the-scope clip (Padlock Clip) for colorectal endoscopic full
      thickness resection (eFTR). Patients and methods We prospectively included 26
      patients with lesions < 20 mm. Indications for eFTR were re-resection of the scar
      of a low risk malignant polyp (n = 11), recurrent adenoma in a non-lifting scar
      (n = 10), non-lifting polyp (n = 4), and an adenoma located in a diverticulum (n
      = 1). Results Technical success rate and full-thickness resection rate were 100 %
      (26/26) and 92 % (24/26), respectively. Median procedure time was 43 minutes (IQR
      27 - 56). No complications occurred during the procedure; 3 complications (12 %)
      occurred within 48 hours, of which one was a perforation requiring laparoscopic
      suturing. Specimen volumes from eFTR of scar tissue where the original polyp had
      been >= 20 mm (n = 13) were smaller compared with those from non-scar resections
      or scars where the original polyps had been < 20 mm (n = 13) (median 0.8 vs. 1.5
      cm3, P = 0.03). Conclusions In this first series of colorectal eFTR using the
      Padlock Clip, feasibility was demonstrated. It was relatively safe in view of
      surgery as the alternative treatment, but could still benefit from technical
      refinement. Future studies should explore for which indication this technique is
      most suitable. TRIAL REGISTRATION: NTR5562 (Dutch Trial Register).

PMID- 28753697
TI  - Post-polypectomy bleeding in the English National Health Service Bowel Cancer
      Screening Programme.
AB  - Background and study aims Colonoscopic polypectomy reduces colorectal cancer
      incidence, but is associated with complications including post-polypectomy
      bleeding (PPB). PPB ranges in severity from minor to life-threatening, making
      interpretation and comparison difficult. No previous studies have examined PPB
      rate according to a standardized severity grading system. We aimed to determine
      the PPB rate stratified by severity grading, explore factors that contribute to
      PPB severity grading, and describe PPB management. Methods Data relating to PPB
      were prospectively collected from all colonoscopies performed in one region of
      the English NHS Bowel Cancer Screening Programme (BCSP) from 06/12/2010 to
      15/07/2014. PPB was defined and stratified into major, intermediate, and minor
      according to BCSP standardized definitions based on the American Society for
      Gastrointestinal Endoscopy adverse events lexicon. Results A total of 15 285
      colonoscopies (23 766 polypectomies) were analyzed. The PPB rate per colonoscopy
      was 0.44 % (95 % confidence interval [CI] 0.34 - 0.54) and the rate per
      polypectomy was 0.29 % (95 %CI 0.20 - 0.38); 2.9 % of PPBs were major and 42.6 %
      were intermediate. Repeat endoscopy occurred in 27.9 % and was the most common
      reason for bleeding being categorized as of intermediate severity, although
      therapy was applied in only 36.8 % of these cases. A therapeutic intervention was
      significantly more common in patients with PPB who had either a hemoglobin drop
      >= 2 g/dL and/or a blood transfusion (P = 0.04, relative risk 3.47, 95 %CI 1.05 -
      11.52). Conclusions This study specifically examined colonoscopic PPB rate,
      stratified using standardized criteria. The rates of PPB were low, with the
      majority of PPB being of minor severity. Current stratification of PPB severity
      combines measures of bleed severity with interventions. Using only hemoglobin
      drop >= 2 g/dL and/or blood transfusion as markers of PPB severity may simplify
      stratification, and allow a better assessment of the necessity and impact of an
      intervention.

PMID- 28753698
TI  - Complete endoscopic sphincterotomy with vs. without large-balloon dilation for
      the removal of large bile duct stones: randomized multicenter study.
AB  - Background and study aims Endoscopic sphincterotomy plus large-balloon dilation
      (ES-LBD) has been reported as an alternative to endoscopic sphincterotomy for the
      removal of bile duct stones. This multicenter study compared complete endoscopic
      sphincterotomy with vs. without large-balloon dilation for the removal of large
      bile duct stones. This is the first randomized multicenter study to evaluate
      these procedures in patients with exclusively large common bile duct (CBD)
      stones. Methods Between 2010 and 2015, 150 patients with one or more common bile
      duct stones >= 13 mm were randomized to two groups: 73 without balloon dilation
      (conventional group), 77 with balloon dilation (ES-LBD group). Mechanical
      lithotripsy was subsequently performed only if the stones were too large for
      removal through the papilla. Endoscopic sphincterotomy was complete in both
      groups. Patients could switch to ES-LBD if the conventional procedure failed.
      Results There was no between-group difference in number and size of stones. CBD
      stone clearance was achieved in 74.0 % of patients in the conventional group and
      96.1 % of patients in the ES-LBD group (P < 0.001). Mechanical lithotripsy was
      needed significantly more often in the conventional group (35.6 % vs. 3.9 %; P <
      0.001). There was no difference in terms of morbidity (9.3 % in the conventional
      group vs. 8.1 % in the ES-LBD group; P = 0.82). The cost and procedure time were
      not significantly different between the groups overall, but became significantly
      higher for patients in the conventional group who underwent mechanical
      lithotripsy. The conventional procedure failed in 19 patients, 15 of whom
      underwent a rescue ES-LBD procedure that successfully cleared all stones.
      Conclusions Complete endoscopic sphincterotomy with large-balloon dilation for
      the removal of large CBD stones has similar safety but superior efficiency to
      conventional treatment, and should be considered as the first-line step in the
      treatment of large bile duct stones and in rescue treatment.Trial registered at
      ClinicalTrials.gov (NCT02592811).

PMID- 28753699
TI  - Calculating the adenoma detection rate in screening colonoscopies only: Is it
      necessary? Can it be gamed?
AB  - Background Current recommendations are to calculate the adenoma detection rate
      (ADR) in screening colonoscopies only. The need to confine the measure to
      screening has not been established. Methods We retrospectively assessed our
      quality database for whether calculating ADR from screening, surveillance, and
      diagnostic colonoscopies (overall ADR) would alter conclusions about the
      performance of colonoscopists, compared to using an ADR based only on screening
      colonoscopies. We also prospectively tested the extent to which one physician
      could corrupt the screening-only ADR by changing the procedure indication after
      reviewing the examination findings. Results For 15 physicians, screening ADRs
      differed from the overall ADR by a mean of 2.6 percentage points (range 0 - 6.9
      percentage points). Using the overall ADR rather than screening ADR changed the
      ADR from just below to just above the recommended screening threshold for one
      physician. In the prospective assessment, a single expert colonoscopist utilized
      indication gaming in patients with both screening and diagnostic indications and
      was able to increase his apparent screening-only ADR from 48.4 % to 55.1 %.
      Conclusions Use of an overall ADR rather than screening-only ADR could simplify
      ADR measurement, increase the number of examinations available to measure ADR,
      seldom affect whether a doctor meets recommended ADR thresholds, and eliminate
      the potential for gaming the ADR by changing the colonoscopy indication.

PMID- 28753700
TI  - A new composite measure of colonoscopy: the Performance Indicator of Colonic
      Intubation (PICI).
AB  - BACKGROUND AND STUDY AIM: Cecal intubation rate (CIR) is an established
      performance indicator of colonoscopy. In some patients, cecal intubation with
      acceptable tolerance is only achieved with additional sedation. This study
      proposes a composite Performance Indicator of Colonic Intubation (PICI), which
      combines CIR, comfort, and sedation. METHODS : Data from 20 085 colonoscopies
      reported in the 2011 UK national audit were analyzed. PICI was defined as the
      percentage of procedures achieving cecal intubation with median dose (2 mg) of
      midazolam or less, and nurse-assessed comfort score of 1 - 3/5. Multivariate
      logistic regression analysis evaluated possible associations between PICI and
      patient, unit, colonoscopist, and diagnostic factors. RESULTS : PICI was achieved
      in 54.1 % of procedures. PICI identified factors affecting performance more
      frequently than single measures such as CIR and polyp detection, or CIR + comfort
      alone. Older age, male sex, adequate bowel preparation, and a positive fecal
      occult blood test as indication were associated with a higher PICI. Unit
      accreditation, the presence of magnetic imagers in the unit, greater annual
      volume, fewer years' experience, and higher training/trainer status were
      associated with higher PICI rates. Procedures in which PICI was achieved were
      associated with significantly higher polyp detection rates than when PICI was not
      achieved. CONCLUSIONS : PICI provides a simpler picture of performance of
      colonoscopic intubation than separate measures of CIR, comfort, and sedation. It
      is associated with more factors that are amenable to change that might improve
      performance and with higher likelihood of polyp detection. It is proposed that
      PICI becomes the key performance indicator for intubation of the colon in
      colonoscopy quality improvement initiatives.

PMID- 28753701
TI  - Reprocessing of single-use endoscopic variceal band ligation devices: a pilot
      study.
AB  - Background and study aims The preferred management of bleeding esophageal varices
      includes endoscopic band ligation. Endoscopic ligation devices (ELDs) are
      expensive and designed for single use, limiting their uptake in developing
      countries. We aimed to assess the efficacy of reprocessing ELDs using terminal
      microbial cultures and adenosine triphosphate (ATP) testing. Materials and
      methods ELDs were recovered after clinical use and their components (cap, handle,
      and cord) were subjected to reprocessing. This included manual cleaning,
      automated high-level disinfection (HLD), and drying with forced air. Using
      sterile technique, ELD components were sampled for ATP at three stages: before
      manual cleaning, after manual cleaning, and after HLD. Components were sent to an
      external laboratory for culturing. Cultures were interpreted as positive upon
      identification of Gram-negative bacilli. Results A total of 14 clinically used
      ELDs were studied, and 189 ATP tests and 41 cultures were evaluated. Overall, 95
      % (39/41) of components and 86 % (12/14) of ELDs were culture-negative or did not
      yield Gram-negative bacilli. Two components (5 %; one handle and one cord)
      harbored Gram-negative bacilli in quantities of 1 CFU per component. There was no
      apparent correlation between ATP at any juncture of reprocessing and terminal
      cultures. Conclusions Reprocessing of ELDs is effective, resulting in infrequent
      and minimal microbial contamination. Microbial culturing can be used to ensure
      adequacy of ELD reprocessing if pursued. Until reusable ELDs are commercially
      available, continued efforts to better define the adequacy and long-term effects
      of reprocessing ELDs are needed.

PMID- 28753702
TI  - Probe-based endomicroscopy for in vivo detection of gastric intestinal metaplasia
      and neoplasia: a multicenter randomized controlled trial.
AB  - Background and study aims Owing to the indistinctive endoscopic appearance of
      gastric intestinal metaplasia (GIM), gastric intraepithelial neoplasia (GIN), and
      early gastric cancer (EGC), a significant number of such lesions may be missed
      during surveillance endoscopy. The aim of this clinical trial was to assess the
      value of combined computed virtual chromoendoscopy (flexible spectral imaging
      color enhancement [FICE]) and probe-based confocal laser endomicroscopy (pCLE)
      for in vivo detection of GIM, GIN, and EGC. Patients and methods This was a
      multicenter, randomized controlled trial performed in 238 patients at four
      tertiary centers. Patients were randomized to FICE-guided pCLE with targeted
      biopsies (group A) or FICE with standard biopsies (group B). The diagnostic yield
      of GIM, GIN, or EGC was compared between the two groups. Results On a per-patient
      assessment, the diagnostic yield for GIM/GIN/EGC was 73.3 % (88/120) in group A
      and 63.6 % (75/118) in group B (P = 0.09). On a per-biopsy analysis, FICE-guided
      pCLE with targeted biopsies significantly increased the diagnostic yield of
      GIM/GIN/EGC vs. FICE with standard biopsies, from 31.5 % (252/800) to 75.1 %
      (313/417) (P < 0.001). In addition, pCLE-guided targeted biopsies led to a
      significant 48.5 % decrease in the number of biopsies per patient vs. FICE with
      standard biopsies (P < 0.001). Conclusions Real-time pCLE and targeted biopsies
      after FICE improved the diagnostic yield for the detection of GIM, GIN, and EGC,
      and only required about half the number of biopsies vs. FICE with standard
      biopsies. This may allow a better regimen for endoscopic surveillance and
      subsequent treatment of patients with premalignant and malignant gastric
      abnormalities.Trial registered at ClinicalTrials.gov (NCT02515721).

PMID- 28753703
TI  - [A Rare Cause of a Spontaneous Pneumothorax].
AB  - A young patient presented himself to the emergency department with sudden-onset,
      breathing-dependent right-sided thoracic pain. The auscultation revealed
      diminished breath sounds on the right. The radiograph showed a pneumothorax which
      was immediately dealt with chest tube drainage. The CT scan of the thorax showed
      minuscule subpleural bullae. Video-assisted thoracoscopic surgery (VATS) was
      performed due to persistent fistulae formation through the drain. The subpleural,
      bullous and emphysematous changes were histologically confirmed. Investigations
      into the cause showed evidence of alpha-1-antitrypsin deficiency (AATD). The
      patient is a Pi MZ type. Few cases of spontaneous pneumothorax as the first
      manifestation of alpha-1-antitrypsin deficiency have been described. Conclusion:
      When diagnosing primary spontaneous pneumothorax, alpha-1-antitrypsin deficiency
      should be considered.

PMID- 28753704
TI  - [Sleep Apnea and Mechanical Ventilation - Impact on Clinical Course and
      Perioperative Management].
AB  - There is a high prevalence of sleep related breathing disorders in critical ill
      patients and in perioperative settings. Nevertheless, less is known about their
      impact on clinical course and therapeutic strategies in this context. Intensive
      care physicians should be aware of difficult airway, weaning- and post-extubation
      failure and negative impact of SRBD on hemodynamics. Sedatives and analgetics
      might worsen SRBD and their use should be restricted as far as possible,
      furthermore the use of NIV might be beneficial. However, there is a lack of
      evidence with regard to this strategies.

PMID- 28753705
TI  - [Workers' Compensation Claims for Needlestick Injuries Among Healthcare Personnel
      in Hospitals, Doctors' Surgeries and Nursing Institutions].
AB  - OBJECTIVE: The "Technical rules for biological agents in healthcare and welfare
      facilities" (TRBA 250) came into force in March 2014 in Germany and deals with
      protective measures to prevent needlestick injuries (NSI). The present study
      covers the period of 6 months after TRBA 250 came into force. The study had 2
      objectives: to investigate whether hospitals, doctors' surgeries and care
      facilities differ with respect to the causes of needlestick injuries (NSI) and to
      collect data on availability and implementation of safety-engineered devices
      (SED) in these healthcare settings workplaces. METHODS: This study analyses
      workers' compensation claims for NSI, as received by the Institution for
      Statutory Accident Insurance and Prevention in the Health and Welfare Services
      (Berufsgenossenschaft fur Gesundheitsdienst und Wohlfahrtspflege, BGW) (n=1602).
      During a telephone interview (response rate 33.3%), the subjects were asked about
      the course of the accident and the handling of SED at the workplace. Descriptive
      analyses were performed for hospitals, doctors' surgeries and care facilities
      (including inpatient care for the elderly and outpatient care). RESULTS: In all 3
      settings, about half of the NSI did not occur during the invasive procedure, but
      during the subsequent disposal of the instruments. 30% of all NSI were caused by
      needles for subcutaneous injections; in care facilities, the proportion was above
      50%. SED were involved in 20% of the NSI in hospitals and doctors' surgeries and
      in 10% of NSI in care facilities. Lack of experience in activating the safety
      mechanism was the most important cause of failure for NSI with SED. SED were
      available at the workplace in 80% of hospitals and doctors' surgeries and in 50%
      of care facilities. CONCLUSION: Training on the safe disposal of sharp
      instruments should be provided to all professional groups who come into contact
      with such instruments. It is currently not possible to provide a reliable
      estimate of the risk of infection from subcutaneous needles. As a high proportion
      of NSI in nursing homes and outpatient care services were caused by subcutaneous
      needles, training on safe handling practices for disposal of needles is needed in
      these settings.

PMID- 28753706
TI  - [Benefit Assessment for Examination and Treatment Methods with Medical Devices of
      High Hisk: Trade-off between Patient Benefit, Evidence and Access].
AB  - The lately inured S 137 h SGB V aims to assess the benefit of new examination and
      treatment methods with medical devices of class IIb and III. In the future, the
      decision on the reimbursement eligibility will be marked by high requirements in
      terms of documentation of benefits and harm. The objective of benefit assessment
      is the operationalization of benefit to patients. A comparative determination of
      benefit enables rational decision by regulatory authorities. The process of
      benefit assessment should guarantee transparent decision-making, and the
      underlying medical and health economic fundamentals should be documented. In
      principle, benefit assessment can be divided into 3 phases: measuring causal
      effects of an intervention, assessment of the measured effects and decision on
      reimbursement based on the aggregation of an overall benefit. To address the
      peculiarities of medical devices in this process, adaptive study designs, MCDA
      and adaptive benefit assessment provide a sustainable concept for rapid access by
      patients to innovative treatments of high quality and safety.

PMID- 28753708
TI  - The Nose and Its Function.

PMID- 28753709
TI  - Nose and Identity.

PMID- 28753710
TI  - Determinants and Evaluation of Nasal Airflow Perception.

PMID- 28753711
TI  - Objective Assessment of Nasal Patency.

PMID- 28753712
TI  - Numerical Analysis of Nasal Breathing: A Pilot Study.

PMID- 28753713
TI  - The Human Sense of Olfaction.

PMID- 28753714
TI  - Auricular Composite Grafting in Functional Rhinoplasty.

PMID- 28753715
TI  - Care of the Cocaine User with Nasal Deformity.

PMID- 28753716
TI  - Facial Defect Reconstruction with Scalp Skin Grafts.

PMID- 28753717
TI  - Is Selfie a New Cause of Increasing Rhinoplasties?

PMID- 28753718
TI  - Do Patients Access Appropriate Information Online?

PMID- 28753719
TI  - Minimally Invasive Aesthetic Procedures: An Update on a Decade-Old Prediction.

PMID- 28753720
TI  - Platelet-Rich Plasma for the Aesthetic Surgeon.

PMID- 28753721
TI  - Geometric Modeling of the Nasal Valve.

PMID- 28753722
TI  - Lateral Wall Insufficiency after Septal Reconstruction.

PMID- 28753723
TI  - Classification of Spreader Flap Techniques.

PMID- 28753724
TI  - Flap Delay or Not? A Technical Detail for Nasal Reconstruction with a Forehead
      Flap.

PMID- 28753725
TI  - Visual Assessment and the Use of the Scar Cosmesis Assessment and Rating Scale
      (SCAR Scale) for Facial Linear Scars.

PMID- 28753726
TI  - Erratum: Effects of Tumescent Solution on Fat Survival.

PMID- 28753727
TI  - Enrichment of Bread with Nutraceutical-Rich Mushrooms: Impact of Auricularia
      auricula (Mushroom) Flour Upon Quality Attributes of Wheat Dough and Bread.
AB  - Edible mushrooms contain a variety of bioactive molecules that may enhance human
      health and wellbeing. Consequently, there is increasing interest in fortifying
      functional foods with these nutraceutical-rich substances. However, incorporation
      of mushroom-based ingredients into foods should not adversely affect the quality
      attributes of the final product. In this study, the impact of incorporating
      powdered Auricularia auricula, a widely consumed edible mushroom, into bread
      products was examined. The rheological and structural properties of wheat dough
      and bread supplemented with 0% to 10% (w/w) A. auricula flour were measured.
      Supplementation of wheat doughs with A. auricula flour increased the peak
      viscosity and enhanced their water holding capacity. Rapid viscosity analysis
      showed that peak and final viscosities of the blended flour (wheat flour with A.
      auricula flour) were higher than wheat flour alone. However, dough stability and
      elastic modulus were reduced by blending wheat flour with A. auricula flour. SEM
      observation showed that doughs with up to 5% (w/w) A. auricula flour had
      acceptable gluten network microstructure. Characterization of the quality
      attributes of bread indicated that incorporation of A. auricula flour at levels
      >5% negatively impacted bread volume, height, texture, and appearance.

PMID- 28753728
TI  - Starch Structure Influences Its Digestibility: A Review.
AB  - Twenty-five years ago, it was found that a significant fraction of the starch
      present in foods is not digested in the small intestine and continues to the
      large intestine, where it is fermented by the microbiota; this fraction was named
      resistant starch (RS). It was also reported that there is a fraction of starch
      that is slowly digested, sustaining a release of glucose in the small intestine.
      Later, health benefits were found to be associated with the consumption of this
      fraction, called slowly digestible starch (SDS). The authors declare both
      fractions to be "nutraceutical starch." An overview of the structure of both
      fractions (RS and SDS), as well as their nutraceutical characteristics, is
      presented with the objective of suggesting methods and processes that will
      increase both fractions in starchy foods and prevent diseases that are associated
      with the consumption of glycemic carbohydrates.

PMID- 28753729
TI  - Safety Evaluation of Green Tea Polyphenols Consumption in Middle-aged
      Ovariectomized Rat Model.
AB  - This work evaluates chronic safety in middle-aged ovariectomized rats
      supplemented with different dosages of green tea polyphenols (GTP) in drinking
      water. The experiment used 6-mo-old sham (n = 39) and ovariectomized (OVX, n =
      143) female rats. All sham (n = 39) and 39 of the OVX animals received no GTP
      treatment and their samples were collected for outcome measures at baseline, 3
      mo, and 6 mo (n = 13 per group for each). The remaining OVX animals were
      randomized into 4 groups receiving 0.15%, 0.5%, 1%, and 1.5% (n = 26 for each) of
      GTP (wt/vol), respectively, in drinking water for 3 and 6 mo. No mortality or
      abnormal treatment-related findings in clinical observations or ophthalmologic
      examinations were noted. No treatment-related macroscopic or microscopic findings
      were noted for animals administered 1.5% GTP supplementation. Throughout the
      study, there was no difference in the body weight among all OVX groups. In all
      OVX groups, feed intake and water consumption significantly decreased with GTP
      dose throughout the study period. At 6 mo, GTP intake did not affect hematology,
      clinical chemistry, and urinalysis, except for phosphorus and blood urea nitrogen
      (increased), total cholesterol, lactate dehydrogenase, and urine pH (decreased).
      This study reveals that the no-observed-adverse-effect level (NOAEL) of GTP is
      1.5% (wt/vol) in drinking water, the highest dose used in this study.

PMID- 28753730
TI  - A Microfluidic Device for Rapid Screening of E. coli O157:H7 Based on IFAST and
      ATP Bioluminescence Assay for Water Analysis.
AB  - We present a simple microfluidic system for rapid screening of Escherichia coli
      (E. coli) O157:H7 employing the specificity of immunomagnetic separation (IMS)
      via immiscible filtration assisted by surface tension (IFAST), and the
      sensitivity of the subsequent adenosine triphosphate (ATP) assay by the
      bioluminescence luciferin/luciferase reaction. The developed device was capable
      of detecting E. coli O157:H7 from just 6 colony forming units (CFU) in 1 mL
      spiked buffer within 20 min. When tested with wastewater discharged effluent
      samples, without pre-concentration, the device demonstrated the ability to detect
      104  CFU per mL seeded; suggesting great potential for point-of-need
      microbiological water quality monitoring.

PMID- 28753731
TI  - Enantioselective Synthesis of Quaternary Delta4 - and Delta5 -Dehydroprolines
      Based on a Two-Step Formal [3+2] Cycloaddition of alpha-Aryl and alpha-Alkyl
      Isocyano(thio)acetates with Vinyl Ketones.
AB  - A divergent synthesis of optically active quaternary Delta4 - and Delta5 -dehydro
      prolines is developed based on the first catalytic enantioselective conjugate
      addition of alpha-substituted isocyano(thio)acetates to vinyl ketones that is
      general for both alpha-aryl and alpha-alkyl isocyano(thio)acetates. The new
      tetrasubstituted C-N stereocenter is formed without the need of any metal salt
      due to a bifunctional tertiary amine/squaramide catalyst, featuring a bulky
      polyaryl sidearm and an unusually short squaramide diamide H???H interatomic
      distance in the solid state.

PMID- 28753732
TI  - The 22-item Sino-Nasal Outcome Test accurately reflects patient-reported control
      of chronic rhinosinusitis symptomatology.
AB  - BACKGROUND: Patient-reported control of chronic rhinosinusitis (CRS) symptoms is
      associated with the quality of life impact of CRS. We sought to determine if 22
      item Sino-Nasal Outcome Test (SNOT-22) score is predictive of patient-perceived
      CRS symptom control. METHODS: Prospective cross-sectional study of 202 patients
      with CRS. Participants were asked to rate their CRS symptom control as "not at
      all," "a little," "somewhat," "very," and "completely." The severity of patient
      CRS symptomatology was measured using the SNOT-22. The relationship between SNOT
      22 score and patient-reported CRS symptom control was determined using
      regression, analysis of variance (ANOVA), and receiver operating characteristic
      (ROC) curve analysis. RESULTS: SNOT-22 was negatively associated with patient
      reported CRS symptom control (adjusted beta = -0.03; 95% CI, -0.04 to -0.02; p <
      0.001), after controlling for demographic and clinical characteristics. There was
      a significant difference in SNOT-22 scores of participants reporting each level
      of symptom control (p < 0.001) with the greatest differences between participants
      who rated their CRS symptom control as "not at all," "a little," and "somewhat,"
      which we deem poor CRS symptom control, and the group who described their level
      of CRS symptom control described as "very" and "completely," which we deem well
      controlled CRS symptoms. These results were true across all SNOT-22 subdomains
      scores as well. Using ROC analysis, a SNOT-22 score of 35 identified patients
      reporting poor vs well-controlled CRS symptom control with 71.4% sensitivity and
      85.5% specificity. CONCLUSION: SNOT-22 score is associated with how well patients
      feel their CRS symptomatology is controlled. Moreover, SNOT-22 score can be used
      to accurately distinguish patients with poor vs well-controlled CRS symptoms.

PMID- 28753733
TI  - Lost in Translation: No Effect of a High-Profile Publication on the Concomitant
      Use of Interacting Drugs.
AB  - We sought to assess whether a high-profile publication that demonstrated serious
      clinical consequences of specific drug-drug interactions (DDIs) reduced the
      concomitant use of those drugs. We conducted a quasi-experimental study using
      2000-2008 prescription claims from a commercial health insurer to examine trends
      in the dispensing of the interacting drug pairs (angiotensin-converting enzyme
      inhibitors[ACEI] + potassium-sparing diuretic, digoxin + clarithromycin, and
      glyburide + cotrimoxazole) and control drug pairs previously reported in a top
      tier general medicine journal. We examined prepublication and postpublication
      dispensing trends using Poisson regression. ACEI + potassium-sparing diuretic use
      did not differ postpublication vs. prepublication (P = 0.11). Digoxin +
      clarithromycin use decreased minimally postpublication vs. prepublication
      (relative rate = 0.9996: 95% confidence interval [CI] = 0.9993-0.9998). Glyburide
      + cotrimoxazole use increased minimally postpublication vs. prepublication
      (relative rate = 1.0220; 95% CI = 1.0187-1.0254). Therefore, the high-profile DDI
      publication had minimal to no measurable effect in reducing the concomitant use
      of the interacting drugs studied. We believe that better strategies are needed to
      translate knowledge about DDIs into clinical practice.

PMID- 28753734
TI  - Negative ions, molecular electron affinity and orbital structure of cata
      condensed polycyclic aromatic hydrocarbons.
AB  - RATIONALE: Polycyclic aromatic hydrocarbons are molecules of ecological,
      astrochemical significance that find practical applications in organic
      electronics, photonics and the chemical synthesis of novel materials. The utility
      of these molecules often implies the occurrence of their ionized forms. Studies
      in the gas phase of elementary processes of energy-controlled interaction of
      molecules with low-energy electrons shed light on the mechanisms of transient
      negative ion formation and evolution. METHODS: Experiments with the individual
      compounds representing homologous and/or isomeric series of cata-condensed
      polyaromatic hydrocarbons were carried out by means of negative ion mass
      spectrometry in the resonant electron capture mode. Literature data obtained by
      complementary techniques and theoretical quantum chemical methods (ab initio and
      density functional theory (DFT)) were invoked to treat the experimental
      observations. RESULTS: Most polycyclic aromatic hydrocarbon (PAH) molecules form
      long-lived molecular negative ions when exposed to free electrons of thermal or
      epi-thermal energy, and no fragmentation is observed up to ca 5 eV. The lifetimes
      of such ions with respect to the spontaneous loss of extra-electron vary from
      tens of microseconds for angular and branched PAH molecules to milliseconds for
      linear ones, and correlate with the adiabatic electron affinity (EA) of
      molecules. Detailed analysis of the electronic (orbital) structure of the
      molecules made it possible to rationalize the relatively low EAs of angular and
      branched PAH compared with those of linear ones. CONCLUSIONS: The obtained
      results contribute to the field of electron-molecule interactions and may be of
      importance for the better comprehension of the functioning of organic
      electronics, for the synthesis of relevant novel materials, and the development
      of efficient analytical methods capable of discriminating structural isomers.

PMID- 28753735
TI  - Isovalent AgIII /AgIII , AgII /AgII , Mixed-Valent AgII /AgIII , and Corrolato
      Based Mixed-Valency in beta,beta'-Linked [Bis{corrolato-silver}]n Complexes.
AB  - Mixed-valent compounds are fascinating entities that are useful as models for
      investigating electron-transfer reactions, and find use in a host of biologically
      relevant redox processes. Though the bio-relevant metal copper is well
      established in mixed-valent chemistry, the AgII /AgIII mixed-valent combination
      of its higher congener in a molecular complex has rarely been reported before.
      This work reports the synthesis of a new beta,beta'-linked bis{corrolato
      silver(III)} complex and its characterization in five different redox states. A
      combination of electrochemistry, spectroelectrochemistry, and DFT calculations
      point to the existence of a mixed-valent AgII /AgIII and an isovalent AgII /AgII
      form. Additionally, characterization of the AgIII /AgIII form and ligand-based
      corrolato-centered mixed-valency is presented as well. These results thus open
      new avenues for bis-corrolato ligands and for mixed-valency in disilver
      compounds.

PMID- 28753736
TI  - Can quantity of amniotic fluid reliably predict postnatal renal function in boys
      with posterior urethral valves: a decision curve analysis.
AB  - OBJECTIVE: Prenatal management of male fetuses with suspected posterior urethral
      valves depends on reliable markers for postnatal long-term renal function.
      Whether ultrasound parameters, including the presence or absence of
      oligohydramnios, are reliable remains the subject of debate. We decided to
      evaluate the reliability of quantity of amniotic fluid to predict postnatal renal
      function using decision curve analysis (DCA), a method for evaluating the
      clinical utility of a diagnostic test. METHODS: We analyzed retrospectively 51
      male fetuses born with prenatally suspected posterior urethral valves between
      2009 and 2012. We studied the relationship between quantity of amniotic fluid on
      prenatal ultrasound and the nadir creatinine during the first year of life as a
      proxy of postnatal renal function using DCA. RESULTS: Twelve fetuses presented
      with prenatal oligohydramnios. Thirty-one children had a normal nadir creatinine,
      of which one had prenatal oligohydramnios (3.2%). Thirteen had a nadir creatinine
      between 35 and 75 MUmol/L, of which four had prenatal oligohydramnios (30.8%).
      Seven had a nadir creatinine >75 MUmol/L, all of them had prenatal
      oligohydramnios. CONCLUSION: In this retrospective study, DCA confirms the
      relationship between prenatal quantity of amniotic fluid volume and postnatal
      renal function. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28753737
TI  - UPLC-MS/MS method for therapeutic drug monitoring of 10 antibiotics used in
      intensive care units.
AB  - A large variation in the levels of different beta-lactams and other antibiotics
      used in critically ill patients has been documented. The aim of this study is to
      establish and validate a fast, ultra-performance liquid chromatography-tandem
      mass spectrometry (UPLC-MS/MS) method for the simultaneous analysis of ten
      antibiotics (Meropenem, Cefepime, Ceftazidime, Piperacillin, Benzylpenicillin,
      Ampicillin, Flucloxacillin, Linezolid, and Sulfamethoxazole/Trimethoprim) in
      human plasma according to European Medicines Agency (EMA) guidelines. Protein
      precipitation with ice-cold methanol containing 9 isotopically labeled internal
      standards was used for sample clean up. Antibiotics were detected, following a 4
      minute gradient separation, in multiple reactions monitoring (MRM) using API 4000
      instrument equipped with electrospray source operating in positive ion mode. The
      lower limit of quantification was 0.1 mg/L for Meropenem, Ceftazidime,
      Piperacillin, Ampicillin, Flucloxacillin, and Sulfamethoxazole; 0.05 mg/L for
      Cefepime, Benzylpenicillin, and Trimethoprim; and 0.02 mg/L for Linezolid. The
      method proved to be precise and accurate and applicable for therapeutic drug
      monitoring and other pharmacokinetic studies.

PMID- 28753738
TI  - Modification of splenic stiffness on acoustic radiation force impulse parallels
      the variation of portal pressure induced by transjugular intrahepatic
      portosystemic shunt.
AB  - BACKGROUND AND AIM: Spleen and liver stiffness (LS) measured by acoustic
      radiation force impulse (ARFI) imaging has been shown to be useful in identifying
      patients with portal hypertension. The study aims to establish if the
      modification of portal pressure induced by a transjugular intrahepatic
      portosystemic shunt (TIPS) parallels the modification of spleen or LS measured by
      ARFI in order to understand if ARFI may be used to monitor the modification of
      portal pressure in patients with cirrhosis. METHODS: Thirty-eight patients with
      severe portal hypertension underwent LS and spleen stiffness (SS) before TIPS and
      1 week after TIPS. Portal atrial gradient (PAG) was measured before and after the
      shunt opening. RESULTS: Portal atrial gradient decreased significantly from 19.5
      to 6 mmHg (P < 0.001). SS decreased significantly after TIPS (pre-TIPS 3.7 m/s vs
      post-TIPS 3. 1 m/s; P < 0.001), and LS was also significantly modified by TIPS
      (pre-TIPS 2.8 m/s vs post-TIPS 2.4 m/s; P = 0.003). PAG and SS values measured
      before and after TIPS were significantly correlated (r = 0.56; P < 0.001); on the
      other hand, PAG and LS were not (r = 0.19; P = 0.27). Two patients developed a
      persistent hepatic encephalopathy refractory to medical treatment and were
      submitted to the reduction of the stent diameter. The modification of SS was
      parallel to the modification of PAG. CONCLUSION: Spleen stiffness is superior to
      LS in detecting the modification of portal pressure induced by TIPS. This makes
      SS a potential non-invasive method to monitor the modification of portal
      hypertension. Further investigations are needed to establish applicability and
      clinical utility of this promising tool in the treatment of portal hypertension.

PMID- 28753739
TI  - Z-scores for fetal left atrial size and left atrium-descending aorta distance in
      fetuses with isolated total anomalous pulmonary venous connection.
AB  - OBJECTIVES: To construct Z-score reference ranges for fetal left atrial (LA) size
      and left atrium-descending aorta distance (LDD or 'post-LA distance') at 20 to 40
      weeks' gestation and to compare these parameters between fetuses with isolated
      total anomalous pulmonary venous connection (TAPVC) and normal fetuses. METHODS:
      Three hundred thirty-three normal singleton fetuses from 20 to 40 weeks'
      gestation were enrolled in a prospective cross-sectional study. Six
      cardiovascular dimensions were obtained by two-dimensional echocardiography. Z
      score reference ranges of these measurements were determined against gestational
      age (GA) and fetal biometric variables, using regression analysis of the mean and
      standard deviation. Also, we reviewed fetal echocardiograms from ten fetuses with
      postnatal diagnosis of isolated TAPVC and made the measurements on archived
      images. Subsequently, all parameters were compared between the normal and TAPVC
      groups. RESULTS: A simple linear regression model was the best description of the
      mean and standard deviation of most variables in normal cases, with the exception
      of the mean LDD based on GA, which was best fitted by a quadratic regression.
      Fetuses with TAPVC had significantly lower LA size Z-scores [80% (8/10) of which
      were under -2] and increased LDD Z-scores [100% (10/10) of which were greater
      than 2]. Using an LDD Z-score of >2.22 was both highly sensitive (100%) and
      specific (98.5%) for distinguishing between TAPVC and normal hearts. CONCLUSION:
      Normal data and Z-scores of fetal LA size and LDD were provided against GA and
      fetal biometry. This could be useful for quantitative assessment of fetal TAPVC.
      Increased post-LA distance and decreased LA size may be markers for the prenatal
      diagnosis of TAPVC. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28753740
TI  - Photopolymerized micropatterns with high feature frequencies overcome
      chemorepulsive borders to direct neurite growth.
AB  - Developing and regenerating neurites respond to a variety of biophysical and
      biochemical cues in their micro-environment to reach target cells and establish
      appropriate synapses. Defining the hierarchal relationship of both types of cues
      to direct neurite growth carries broad significance for neural development,
      regeneration, and, in particular, engineering of neural prostheses that improve
      tissue integration with native neural networks. In this work, chemorepulsive
      biochemical borders are established on substrates with a range of surface
      microfeatures to determine the potential of physical cues to overcome conflicting
      biochemical cues. Physical micropatterns are fabricated using photomasking
      techniques to spatially control photoinitiation events of the polymerization.
      Temporal control of the reaction allows for generation of microfeatures with the
      same amplitude across a range of feature frequencies or periodicities. The
      micropatterned substrates are then modified with repulsive chemical borders
      between laminin and either EphA4-Fc or tenascin C that compete with the surface
      microfeatures to direct neurite growth. Behaviour of neurites from spiral
      ganglion and trigeminal neurons is characterized at biochemical borders as cross,
      turn, stop, or repel events. Both the chemical borders and physical patterns
      significantly influence neurite pathfinding. On unpatterned surfaces, most
      neurites that originate on laminin are deterred by the border with tenascin C or
      EphA4-Fc. Importantly, substrates with frequent micropattern features overcome
      the influence of the chemorepulsive border to dominate neurite trajectory.
      Designing prosthesis interfaces with appropriate surface features may allow for
      spatially organized neurite outgrowth in vivo even in the presence of conflicting
      biochemical cues in native target tissues.

PMID- 28753741
TI  - Perceived employer-related barriers and facilitators for work participation of
      cancer survivors: A systematic review of employers' and survivors' perspectives.
AB  - OBJECTIVE: To identify employer-related barriers and facilitators for work
      participation of cancer survivors from the perspective of both employers and
      cancer survivors, and to synthesise these perceived barriers and facilitators to
      understand their perceived consequences. METHODS: A systematic review of
      qualitative studies focusing on employers' and cancer survivors' perspectives on
      the work participation of cancer survivors was performed. Four databases
      (MEDLINE, EMBASE, PsycINFO, and Business Source Premier) were systematically
      searched, and the quality of studies included was assessed using the CASP
      checklist. Perceived barriers and facilitators were extracted and synthesised to
      conduct a content analysis. RESULTS: Five studies representing the employers'
      perspectives and 47 studies representing the cancer survivors' perspectives were
      included. Employers perceived barriers and facilitators related to support,
      communication, RTW policies, knowledge about cancer, balancing interests and
      roles, and attitude. Survivors perceived barriers and facilitators related to
      support, communication, work environment, discrimination, and perception of work
      ability. The synthesis found that the employers' willingness to support can be
      understood by perceptions they have of the survivor, goals of the employer, and
      national or organisational policies. Employers require knowledge about cancer and
      RTW policies to be able to support survivors. CONCLUSIONS: This review identified
      a plurality of and a large variety in perceived employer-related barriers and
      facilitators for work participation of cancer survivors, which can be understood
      to be related to both employers' willingness and ability to support. There is a
      need for interventions targeting employers, with the aim of enhancing the
      sustainable work participation of cancer survivors.

PMID- 28753742
TI  - Stress Facilitates the Development of Cognitive Dysfunction After Chronic Ethanol
      Exposure.
AB  - BACKGROUND: Chronic exposure to stress or alcohol can drive neuroadaptations that
      alter cognition. Alterations in cognition may contribute to alcohol use disorders
      by reducing cognitive control over drinking and maintenance of abstinence. Here
      we examined effects of combined ethanol (EtOH) and stress exposure on prefrontal
      cortex (PFC)-dependent cognition. METHODS: Adult male C57BL/6J mice were trained
      to drink EtOH (15%, v/v) on a 1 h/d 1-bottle schedule. Once stable, mice were
      exposed to cycles of chronic intermittent EtOH (CIE) or air-control vapor
      exposure (Air), followed by test cycles of 1 h/d EtOH drinking. During test
      drinking, mice received no stress (NS) or 10 minutes of forced swim stress (FSS)
      4 hours before each test. This schedule produced 4 experimental groups: control,
      Air/NS; EtOH-dependent no stress, CIE/NS; nondependent stress, Air/FSS; or EtOH
      dependent stress, CIE/FSS. After 2 cycles of CIE and FSS exposure, we assessed
      PFC-dependent cognition using object/context recognition and attentional set
      shifting. At the end of the study, mice were perfused and brains were collected
      for measurement of c-Fos activity in PFC and locus coeruleus (LC). RESULTS:
      CIE/FSS mice escalated EtOH intake faster than CIE/NS and consumed more EtOH than
      Air/NS across all test cycles. After 2 cycles of CIE/FSS, mice showed impairments
      in contextual learning and extradimensional set-shifting relative to other
      groups. In addition to cognitive dysfunction, CIE/FSS mice demonstrated
      widespread reductions in c-Fos activity within prelimbic and infralimbic PFC as
      well as LC. CONCLUSIONS: Together, these findings show that interactions between
      EtOH and stress exposure rapidly lead to disruptions in signaling across
      cognitive networks and impairments in PFC-dependent cognitive function.

PMID- 28753743
TI  - Effects of chronic exposure to waterborne copper and nickel in binary mixture on
      tissue-specific metal accumulation and reproduction in fathead minnow (Pimephales
      promelas).
AB  - The current study evaluated the interactive effects of chronic waterborne copper
      (Cu) and nickel (Ni) exposure on tissue-specific metal accumulation and
      reproductive performance in fathead minnow (Pimephales promelas). Fish trios (1
      male: 2 female; n = 5-6) were exposed for 21 days to: (i) control (no added Cu or
      Ni), (ii) waterborne Cu (45 MUg/L), (iii) waterborne Ni (270 MUg/L), and (iv)
      binary mixture of waterborne Cu and Ni (45 and 270 MUg/L, respectively). Fish
      fecundity (cumulative egg production) was found to be the most sensitive
      reproductive endpoint, and the interaction of Cu and Ni elicited an additive
      effect on egg production. Tissue-specific accumulation of both metals was not
      influenced by the interaction of Cu and Ni, except an increased Cu and Ni burden
      in the carcass and ovary, respectively, were recorded. The expressions of hepatic
      estrogen receptor genes (ER-alpha and ER-beta) and the circulating estradiol
      level in females were also not affected by the metal-mixture treatment. However,
      co-exposure to waterborne Cu and Ni resulted in a significant downregulation of
      the hepatic vitellogenin gene in females, which was associated with the maximum
      upregulation of the hepatic metallothionein gene. In addition, a significant
      alteration of ovarian histopathology (decreased abundance of post-vitellogenic
      follicles, and increased follicular atresia) was also observed only in females
      exposed to Cu and Ni in mixture. Collectively, these observations suggest that
      chronic waterborne exposure to Cu and Ni in binary mixture may impair fish
      reproductive capacity by inducing histopathological damage in ovarian tissue, and
      disrupting of energy homeostasis in fish.

PMID- 28753744
TI  - The promotional effect of water-soluble extractives on the enzymatic cellulose
      hydrolysis of pretreated wheat straw.
AB  - Enzymatic cellulose hydrolysis of pretreated wheat straw pulp to glucose is
      enhanced when the hydrolysis is performed in the presence of an aqueous extract
      of the wheat straw. A relative digestibility increase of about 10% has been
      observed for organosolv, alkaline and dilute acid pretreated wheat straw pulp
      (enzyme dose 2.5FPU/g pulp). At lower enzyme doses, the extract effect increases
      leading to an enzyme dose reduction of 40% to obtain a glucose yield of 75%
      within 48h using organosolv wheat straw pulp. Possibly, cellulase deactivation by
      irreversible binding to pulp lignin is reduced by competition with proteins in
      the extract. However, since the extract effect has also been demonstrated for
      lignin-lean substrates, other effects like improved accessibility of the pulp
      cellulose (amorphogenesis) cannot be excluded. Overall, this contribution
      demonstrates the positive effect of biomass extractives on enzymatic cellulose
      digestibility, thereby reducing costs for 2G biofuels and bio-based chemicals.

PMID- 28753745
TI  - In-depth Critical Analysis of Complications Following Robot-assisted Radical
      Cystectomy with Intracorporeal Urinary Diversion.
AB  - BACKGROUND: Robot-assisted radical cystectomy with intracorporeal urinary
      diversion (iRARC) is an attractive option to open cystectomy, but the benefit in
      terms of improved outcomes is not established. OBJECTIVE: To evaluate the early
      postoperative morbidity and mortality of patients undergoing iRARC and conduct a
      critical analysis of complications using standardised reporting criteria as
      stratified according to urinary diversion. DESIGN, SETTING, AND PARTICIPANTS: A
      total of 134 patients underwent iRARC for bladder cancer at a single centre
      between June 2011 and July 2015. INTERVENTION: Radical cystectomy with iRARC.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient demographics, pathologic
      data, and 90-d perioperative mortality and complications were recorded.
      Complications were reported according to the Clavien-Dindo (CD) classification
      and stratified according to urinary diversion type and either surgical or medical
      complications. The chi-square test and t test were used for categorical and
      continuous variables respectively. Multivariable logistic regression was
      performed on variables with significance in univariate analysis. RESULTS AND
      LIMITATIONS: The 90-d all complication rate following ileal conduit and continent
      diversion was 68% and 82.4%, and major complications were 21.0% and 20.6%
      respectively. The 90-d mortality was 3% and 2.9% for ileal conduit and continent
      diversion patients, respectively. On multivariate analysis, the blood transfusion
      requirement was independently associated with major complications (p=0.002) and
      all 30-d (p=0.002) and 90-d (p=0.012) major complications. Male patients were
      associated with 90-d major complications (p=0.015). Critical analysis identified
      that surgical complications were responsible for 39.4% of all 90-d major
      complications. The incidence of surgical complications did not decline with
      increasing number of iRARC cases performed (p=0.742, r=0.31). Limitations of this
      study include its retrospective nature, limited sample size, and limited
      multivariate analysis due to the low number of major complications events.
      CONCLUSIONS: Although complications following iRARC are common, most are low
      grade. A critical analysis identified surgical complications as a cause of major
      complications. Addressing this issue could have a significant impact on lowering
      the morbidity associated with iRARC. PATIENT SUMMARY: We looked at the surgical
      outcomes in bladder cancer patients treated with minimally invasive robotic
      surgery. We found that surgical complications account for most major
      complications and previous surgical experience may be a confounding factor when
      interpreting results from a different centre even in a randomised trial setting.

PMID- 28753746
TI  - Feasibility and Clinical Roles of Different Substaging Systems at First and
      Second Transurethral Resection in Patients with T1 High-Grade Bladder Cancer.
AB  - BACKGROUND: Decision making in T1 high-grade bladder cancer patients remains a
      challenging issue in urologic practice. OBJECTIVE: To assess the feasibility and
      potential prognostic role of three different substaging systems in specimens from
      both primary and second transurethral resection (TUR) of the bladder in T1 high
      grade bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS: A total of 250
      consecutive, confirmed pure transitional T1 high-grade bladder tumors submitted
      to second TUR entered the retrospective study. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Feasibility of two already clinically tested microstaging
      systems (anatomy-based T1a/T1b/T1c and micrometric T1m/T1e with 0.5-mm thresholds
      of invasion) and that of a micrometric substage designed by the authors and based
      on a 1-mm threshold of invasion (Rete Oncologica Lombarda [ROL] system) was
      assessed by five independent uropathologists on both first and second TUR
      specimens. Univariable Cox proportional hazards models were attempted to identify
      significant independent predictors of recurrence and progression after TUR.
      Kaplan-Meier curves were plotted to compare different substaging methods
      analyzing recurrence and progression. RESULTS AND LIMITATIONS: The ROL system
      proved to be feasible in nearly all cases at both first and second TUR. Median
      follow-up was 60 mo. The univariate Cox regression analysis documented the ROL
      substage (ROL2 vs ROL1) to be the only statistically significant predictor of
      progression (hazard ratio: 2.01; 95% CI, 1.03-3.79; p<0.03). For the first time
      to our knowledge, the substage was investigated and used to assess T1 tumors
      found at second TUR, registering a high rate of feasibility. CONCLUSIONS: T1
      microstaging using different procedures is feasible on both primary- and second
      TUR specimens. A high rate of feasibility may be expected for T1m/T1e and ROL
      systems. The clinical role of microstaging on second TUR remains to be defined.
      PATIENT SUMMARY: The Rete Oncologica Lombarda system showed feasible results in
      T1 high-grade bladder tumors. Our substratification was predictive of progression
      of disease.

PMID- 28753747
TI  - Factors Predicting the Off-treatment Duration in Patients with Prostate Cancer
      Receiving Degarelix as Intermittent Androgen Deprivation Therapy.
AB  - BACKGROUND: Intermittent androgen deprivation therapy (IAD) is commonly used in
      prostate cancer because of the benefits of the off-treatment period (OTP). The
      off-treatment time for patients depends on cancer progression, often measured as
      a rise in prostate-specific antigen (PSA). OBJECTIVE: To evaluate if certain
      factors can predict OTP duration following 7-mo degarelix therapy. DESIGN,
      SETTING, AND PARTICIPANTS: This multivariable analysis included 191 prostate
      cancer patients with baseline PSA 4-50 ng/ml or PSA doubling time <24 mo entering
      the first OTP with PSA <=4 ng/ml and testosterone <0.5 ng/ml. OTP continued until
      disease progression, measured as PSA >4 ng/ml. Despite a study-defined OTP
      maximum of 24 mo, a 50% failure rate was not observed within certain strata. A
      Weibull distribution was used to estimate median time to PSA >4 ng/ml adjusted
      for the following variables: age; baseline (or end of induction period [EOI])
      PSA; baseline testosterone; cancer stage/previous curative treatment; and Gleason
      score. According to the results and the utility of these factors in clinical
      practice, the model was reduced in a stepwise manner. Time to testosterone
      recovery (testosterone >0.5 and >2.2 ng/ml) was estimated in a similar manner.
      RESULTS: The full five-factor model showed that baseline PSA (p<0.0001), age
      (p=0.004), prostate cancer stage/previous therapy (p=0.023), and baseline
      testosterone (p=0.039) influenced OTP. A reduced two-factor model (baseline PSA,
      age) showed that only baseline PSA influenced OTP (p<0.0001), and patients with
      baseline PSA <=4 ng/ml had the longest OTP. In addition, EOI PSA (p<0.0001) and
      age (p=0.050) significantly influenced OTP. The times to testosterone >0.5 and
      >2.2 ng/ml were longer for older patients and those with lower baseline
      testosterone levels. CONCLUSION: Patients with lower baseline and EOI PSA, and
      older patients can stay off therapy longer and therefore may benefit more from
      degarelix IAD. These factors may help in proposing an algorithm to predict the
      OTP and optimise visit frequency. PATIENT SUMMARY: We describe extended analysis
      results for a trial in which patients with prostate cancer received intermittent
      androgen deprivation treatment. Prostate-specific antigen levels at baseline and
      at the end of the induction period, as well as older age, predicted the duration
      of the off-treatment period. Testosterone recovery was slower in older patients
      and in patients who had lower pretreatment testosterone levels. These factors may
      help in deciding whether to choose continuous or intermittent treatment as a
      strategy. TRIAL REGISTRATION: Clinicaltrials.gov NCT00801242.

PMID- 28753748
TI  - Integrated Biosensor Assay for Rapid Uropathogen Identification and Phenotypic
      Antimicrobial Susceptibility Testing.
AB  - BACKGROUND: Standard diagnosis of urinary tract infection (UTI) via urine culture
      for pathogen identification (ID) and antimicrobial susceptibility testing (AST)
      takes 2-3 d. This delay results in empiric treatment and contributes to the
      misuse of antibiotics and the rise of resistant pathogens. A rapid diagnostic
      test for UTI may improve patient care and antibiotic stewardship. OBJECTIVE: To
      develop and validate an integrated biosensor assay for UTI diagnosis, including
      pathogen ID and AST, with determination of the minimum inhibitory concentration
      (MIC) for ciprofloxacin. DESIGN, SETTING, AND PARTICIPANTS: Urine samples
      positive for Enterobacteriaceae (n=84) or culture-negative (n=23) were obtained
      from the Stanford Clinical Microbiology Laboratory between November 2013 and
      September 2014. Each sample was diluted and cultured for 5h with and without
      ciprofloxacin, followed by quantitative detection of bacterial 16S rRNA using a
      single electrochemical biosensor array functionalized with a panel of
      complementary DNA probes. Pathogen ID was determined using universal bacterial,
      Enterobacteriaceae (EB), and pathogen-specific probes. Phenotypic AST with
      ciprofloxacin MIC was determined using an EB probe to measure 16S rRNA levels as
      a function of bacterial growth. MEASUREMENTS: Electrochemical signals for
      pathogen ID at 6 SD over background were considered positive. An MIC signal of
      0.4 log units lower than the no-antibiotic control indicated sensitivity. Results
      were compared to clinical microbiology reports. RESULTS AND LIMITATIONS: For
      pathogen ID, the assay had 98.5% sensitivity, 96.6% specificity, 93.0% positive
      predictive value, and 99.3% negative predictive value. For ciprofloxacin MIC the
      categorical and essential agreement was 97.6%. Further automation, testing of
      additional pathogens and antibiotics, and a full prospective study will be
      necessary for translation to clinical use. CONCLUSIONS: The integrated biosensor
      platform achieved microbiological results including MIC comparable to standard
      culture in a significantly shorter assay time. Further assay automation will
      allow clinical translation for rapid molecular diagnosis of UTI. PATIENT SUMMARY:
      We have developed and validated a biosensor test for rapid diagnosis of urinary
      tract infections. Clinical translation of this device has the potential to
      significantly expedite and improve treatment of urinary tract infections.

PMID- 28753749
TI  - Comprehensive Genomic Profiling of Renal Cell Carcinoma at Initial Diagnosis and
      Putative Local Recurrence.
AB  - In the context of metastatic renal cell carcinoma, it would typically be assumed
      that the site of recurrence is derived from the original tumor. Through the use
      of comprehensive genomic profiling in a case of localized disease with a
      subsequent recurrence in the renal fossa, we determined that the latter was a
      wholly distinct tumor. The original tumor harbors mutations in PBRM1, while the
      second harbors mutations in KDM5C. These findings, if further validated, could
      prompt caution in interpretation of genomic tests used for risk stratification
      and could have implications for ongoing studies of adjuvant therapy.

PMID- 28753750
TI  - A Longitudinal Analysis of Premature Ejaculation Symptoms Raises Concern
      Regarding the Appropriateness of a "Lifelong" Subtype.
AB  - : Premature ejaculation (PE) is divided into acquired and lifelong subtypes, with
      the implication that the latter is chronic. This longitudinal study included data
      for untreated respondents from a population-based sample (sample 1) and a sample
      of patients diagnosed with lifelong PE (sample 2). About half of the respondents
      who at time 1 fulfilled the most important diagnostic criterion for lifelong PE
      (<=1minute ejaculation latency) no longer did so at time 2. Standardised
      autoregressive coefficients for PE symptom measures were 0.58 for sample 1, 0.83
      for sample 2, and 0.37 for individuals with ejaculatory latencies <=1minute. A
      subjective perception of change in ejaculatory latency was reported by 47%
      (n=397) of sample 1 and 62% (n=10) of sample 2. PE symptoms were in general
      unstable over time, which raises concern regarding the appropriateness of the
      "lifelong" diagnosis. PATIENT SUMMARY: We looked at the stability of symptoms of
      premature ejaculation (PE) over time. We found that PE symptom severity varies
      considerably, and to a lesser but still considerable degree in patients diagnosed
      with lifelong PE. Our results suggest that there is reason to doubt the
      appropriateness of the term lifelong PE.

PMID- 28753751
TI  - Development of Indicators to Assess Quality of Care for Prostate Cancer.
AB  - BACKGROUND: The development, monitoring, and reporting of indicator measures that
      describe standard of care provide the gold standard for assessing quality of care
      and patient outcomes. Although indicator measures have been reported, little
      evidence of their use in measuring and benchmarking performance is available. A
      standard set, defining numerator, denominator, and risk adjustments, will enable
      global benchmarking of quality of care. OBJECTIVE: To develop a set of indicators
      to enable assessment and reporting of quality of care for men with localised
      prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: Candidate indicators
      were identified from the literature. An international panel was invited to
      participate in a modified Delphi process. Teleconferences were held before and
      after each voting round to provide instruction and to review results. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Panellists were asked to rate each
      proposed indicator on a Likert scale of 1-9 in a two-round iterative process.
      Calculations required to report on the endorsed indicators were evaluated and
      modified to reflect the data capture of the Prostate Cancer Outcomes Registry
      Australia and New Zealand (PCOR-ANZ). RESULTS AND LIMITATIONS: A total of 97
      candidate indicators were identified, of which 12 were endorsed. The set includes
      indicators covering pre-, intra-, and post-treatment of PCa care, within the
      limits of the data captured by PCOR-ANZ. CONCLUSIONS: The 12 endorsed quality
      measures enable international benchmarking on the quality of care of men with
      localised PCa. Reporting on these indicators enhances safety and efficacy of
      treatment, reduces variation in care, and can improve patient outcomes. PATIENT
      SUMMARY: PCa has the highest incidence of all cancers in men. Early diagnosis and
      relatively high survival rates mean issues of quality of care and best possible
      health outcomes for patients are important. This paper identifies 12 important
      measurable quality indicators in PCa care.

PMID- 28753752
TI  - Comorbidity and the Receipt of Curative Therapy for Favorable-risk Prostate
      Cancer Prior to and Following the Publication of PIVOT.
AB  - : The publication of the randomized Prostate Cancer Intervention Versus
      Observation Trial (PIVOT) in July 2012, in which men with favorable-risk prostate
      cancer (PCa) were not found to benefit from radical prostatectomy, had the
      potential to shift PCa practice patterns. Using a prospectively assembled
      database of 5398 men with low-risk or favorable intermediate-risk PCa selected
      for curative treatment with brachytherapy in the years preceding and the year
      following the publication of PIVOT, we evaluated the odds of receiving curative
      treatment after adjusting for risk group (favorable intermediate vs low), race
      (black, Hispanic, or other), number of cardiometabolic comorbidities, and age.
      Following publication, the receipt of curative treatment was significantly lower
      (adjusted odds ratio [AOR]: 0.40; 95% confidence interval [CI], 0.16-0.99;
      p=0.05) among men with at least two cardiometabolic comorbidities, in contrast to
      the increasing trend (p=0.02) noted prior to PIVOT. Among black men, a subgroup
      at risk for occult high-grade disease, the odds of receiving curative treatment
      increased after PIVOT (AOR: 1.55; 95% CI, 1.06-2.26; p=0.02). These observations
      suggest that PIVOT's publication appropriately contributed to decreasing the use
      of curative treatment in men unlikely to benefit. PATIENT SUMMARY: The Prostate
      Intervention Versus Observation Trial (PIVOT) showed that radical prostatectomy
      did not benefit men with favorable-risk prostate cancer. Following the
      publication of PIVOT, the selection of men with multiple medical issues for
      curative treatment declined, whereas treatment of men at high risk of having
      aggressive prostate cancer increased.

PMID- 28753753
TI  - The Dangers That Threaten Current Research of Premature Ejaculation: Using
      Validated Questionnaires, Performing Conjuring Tricks with Statistics, and
      Refusing to Use Real-time Stopwatch Measurements of Intravaginal Ejaculation
      Latency Time.

PMID- 28753754
TI  - Delaying Surgical Treatment of Penile Fracture Results in Poor Functional
      Outcomes: Results from a Large Retrospective Multicenter European Study.
AB  - BACKGROUND: Penile fracture is a rare clinical entity that represents a urologic
      emergency. It involves traumatic rupture of the tunica albuginea of the corpora
      cavernosa due to twisting or bending of the penile shaft during erection.
      OBJECTIVE: To determine the differences in preoperative diagnostic evaluation
      patterns and outcomes of penile fracture patients to investigate the impact of
      surgical delay on functional outcomes. DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective analysis was performed using data obtained from 137 patients
      presenting with penile fracture at seven different European academic medical
      centers between 1996 and 2013. Age, imaging modalities used, timing of surgical
      intervention, length of tunica albuginea defect, and surgical technique were
      recorded. Postoperative erectile function outcomes were assessed with the
      International Index of Erectile Function (IIEF-5), and the presence of
      postoperative penile curvature was noted. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: The association between timing of surgical intervention and
      postoperative IIEF-5 results was evaluated with discriminant function analysis.
      RESULTS AND LIMITATIONS: The median age of the patients was 34.50 yr
      (interquartile range [IQR]: 28.0-46.5 yr). Of the 137 patients, 82 (59.85%)
      underwent penile Doppler ultrasound, and 5 patients (3.64%) were evaluated with
      magnetic resonance imaging. All patients were treated surgically, and the
      duration between emergency room admission and surgical intervention was 5.0h
      (IQR: 3.6-8.0h). The median length of tunica albuginea defect was 10mm (IQR: 8
      20mm). Postoperative IIEF-5 scores were 21 (IQR: 12-23) and 23 (IQR: 15-24) at
      the first and third postoperative months, respectively. Discriminant function
      analysis revealed that if the surgical intervention was performed >8.23hours
      after emergency room admission, postoperative erectile function was significantly
      worse (p=0.0051 at first month and p=0.0057 at third month postoperatively).
      CONCLUSIONS: Our multicenter study showed that delaying surgical intervention
      results in significantly impaired erectile function. Surgical treatment must be
      planned as soon as possible to avoid postoperative erectile dysfunction. PATIENT
      SUMMARY: We looked at sexual outcomes following the repair of penile fracture in
      a large European population. We found that outcomes worsened if surgical repair
      was delayed.

PMID- 28753755
TI  - Association between Lymph Node Counts and Oncological Outcomes in Lymph Node
      Positive Prostate Cancer.
AB  - BACKGROUND: While the diagnostic value of pelvic lymph node dissection (PLND)
      during radical prostatectomy (RP) is undisputed, its therapeutic benefit remains
      a matter of debate. OBJECTIVE: To investigate the association between total and
      positive lymph node (LN) counts and oncological outcomes in pN1 patients at RP.
      DESIGN, SETTING, AND PARTICIPANTS: The records of 706 LN-positive patients
      undergoing RP and PLND between 1998 and 2012 in a single center were analyzed.
      The median follow-up was 47.8 mo. INTERVENTION: RP and PLND. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: The number of harvested and positive LNs and their
      influence on biochemical recurrence-free survival, metastasis-free survival, and
      cancer-specific survival was evaluated using univariate and multivariate Cox
      regressions. The number of harvested LNs was used as a continuous and dichotomous
      variable with a cut-off of 13 LNs. RESULTS AND LIMITATIONS: The mean (median)
      number of removed LNs was 15.0 (13) and the mean (median) number of positive LNs
      was 2.4 (1). In multivariate analysis, the number of removed LNs did not
      significantly influence oncologic outcomes (biochemical recurrence, metastasis
      free survival, or cancer-specific survival). The occurrence of metastasis and
      cancer-specific mortality significantly increased with higher number of positive
      LNs. The main limitation was the retrospective nature of the study. CONCLUSIONS:
      While a higher number of positive LNs were significantly associated with worse
      oncological outcomes, the number of removed LNs was not a significant predictor.
      PATIENT SUMMARY: We found that only the number of positive lymph nodes (LNs) but
      not the total number of removed LNs was a factor adversely influencing
      oncological outcomes in LN-positive patients undergoing radical prostatectomy.

PMID- 28753756
TI  - Economic Value of the Transurethral Resection in Saline System for Treatment of
      Benign Prostatic Hyperplasia in England and Wales: Systematic Review, Meta
      analysis, and Cost-Consequence Model.
AB  - CONTEXT: Monopolar transurethral resection of the prostate (M-TURP) is the
      current UK surgical standard of care for benign prostatic hyperplasia, a
      condition estimated to affect >2 million men in the United Kingdom. Although M
      TURP efficacy in prostate resection is established, potential perioperative
      complications and associated costs remain a concern. OBJECTIVE: To present up-to
      date and robust evidence in support of bipolar transurethral resection in saline
      (TURis) as an alternative surgical option to M-TURP. EVIDENCE ACQUISITION: A
      systematic review (SR) of electronic databases (up to 2015) for randomised
      controlled trials (RCTs) comparing TURis with M-TURP was conducted, followed by
      evidence synthesis in the form of a meta-analysis of hospital stay,
      catheterisation time and procedure duration, transurethral resection (TUR)
      syndrome, blood transfusion, clot retention, and urethral strictures. An economic
      analysis was subsequently undertaken from the UK National Health Service hospital
      perspective with costs and resource use data from published sources. EVIDENCE
      SYNTHESIS: The SR identified 15 good-quality RCTs, of which 11 were used to
      inform the meta-analysis. TURis was associated with improved safety versus M
      TURP, eliminating the risk of TUR syndrome and reducing the risk of blood
      transfusion and clot retention (relative risks: 0.34 and 0.43, respectively;
      p<0.05). TURis also reduced hospital stay (mean difference: 0.56 d; p<0.0001).
      The economic analysis indicated potential cost savings with TURis versus M-TURP
      of up to L204 per patient, with incremental equipment costs offset by savings
      from reduced hospital stay and fewer complications. CONCLUSIONS: The TURis system
      is associated with significant improvements in perioperative safety compared with
      M-TURP while ensuring equivalent clinical outcomes of prostate resection. The
      safety benefits identified may translate into cost savings for UK health
      services. PATIENT SUMMARY: Our review of bipolar transurethral resection in
      saline, the new prostate resection technique, indicates that it offers equal
      efficacy while reducing complications and length of hospital stay.

PMID- 28753757
TI  - Quantification of Surgical Delay in Penile Fractures.

PMID- 28753758
TI  - Erratum re: "Surgical Management of Adrenocortical Carcinoma: Impact of
      Laparoscopic Approach, Lymphadenectomy, and Surgical Volume on Outcomes-A
      Systematic Review and Meta-analysis of the Current Literature" [Eur Urol Focus,
      2015; 1 (3) 241-250].

PMID- 28753759
TI  - Curing Lymph Node Metastasis in Prostate Cancer: The Ongoing Battle Between
      Improving Surgical Quality and Tumor Biology.

PMID- 28753760
TI  - Underutilization of Radical Cystectomy Among Patients Diagnosed with Clinical
      Stage T2 Muscle-invasive Bladder Cancer.
AB  - BACKGROUND: Radical cystectomy is the standard surgical treatment for muscle
      invasive bladder cancer (MIBC). OBJECTIVE: We sought to identify population-based
      factors predicting the use of radical cystectomy. DESIGN, SETTING, AND PATIENTS:
      Analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data for
      3922 patients aged >=66 yr diagnosed with clinical stage T2 MIBC from January 1,
      2002 to December 31, 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used
      univariate and multivariable regression analyses to identify factors predicting
      the use of radical cystectomy. Cox proportional hazards models were used to
      analyze survival outcomes. RESULTS AND LIMITATIONS: A total of 740 (18.9%)
      patients with MIBC underwent radical cystectomy. Older age at diagnosis (>80 vs
      65-69 yr, odds ratio [OR] 0.15, 95% confidence interval [CI] 0.11-0.19; p<0.001)
      and higher comorbidity (Charlson comorbidity index 3+ vs 0, OR 0.41, 95% CI 0.29
      0.57; p<0.001) were associated with lower use of radical cystectomy. Moreover,
      non-Hispanic black patients were less likely than white patients to undergo
      radical cystectomy (OR 0.62, 95% CI 0.40-0.96; p=0.032) and pelvic lymph node
      dissection (OR 0.65, 95% CI 0.42-1.02; p=0.058). Overall survival was better for
      patients who underwent radical cystectomy alone (hazard ratio [HR] 0.70, 95% CI
      0.56-0.88; p=0.002) and with lymph node dissection (HR 0.45, 95% CI 0.40-0.51;
      p<0.001). Limitations include the limited ability of retrospective analysis to
      demonstrate causality. CONCLUSIONS: There is significant underutilization of
      radical cystectomy among patients diagnosed with MIBC, especially among older
      patients with significant comorbidities and non-Hispanic black patients. PATIENT
      SUMMARY: Despite guideline recommendations, there is significant underutilization
      of radical cystectomy among patients diagnosed with bladder cancer, especially
      for non-Hispanic black patients and older patients with significant
      comorbidities.

PMID- 28753761
TI  - Reply from Authors re: Marcel D. Waldinger. The Dangers That Threaten Current
      Research of Premature Ejaculation: Using Validated Questionnaires, Performing
      Conjuring Tricks with Statistics, and Refusing to Use Real-Time Stopwatch
      Measurements of Intravaginal Ejaculation Latency Time. Eur Urol Focus. In press.
      http://dx.doi.org/10.1016/j.euf.2016.02.008.

PMID- 28753762
TI  - Statin Use and Prostate Cancer Survival in the Finnish Randomized Study of
      Screening for Prostate Cancer.
AB  - BACKGROUND: Recent research has suggested that statins have an effect on prostate
      cancer prognosis. It is currently unclear how prostate cancer screening, tumor
      and patient characteristics, or treatment selection may affect this association.
      OBJECTIVE: To evaluate the risk of prostate cancer death among statin users. To
      determine how disease and treatment characteristics affect the association.
      DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cohort study
      consisting of a general male population of Finland participating in the Finnish
      Randomized Study for Prostate Cancer Screening. The cohort of consisted of 6537
      prostate cancer cases diagnosed in the Finnish Randomized Study of Screening for
      Prostate Cancer population during 1996-2012. The cohort was linked to the
      National Prescription Database for information on the use of statins and other
      drugs. INTERVENTION: Statin use before and after prostate cancer diagnosis
      compared with nonuse. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Hazard
      ratios (HRs) for the risk of prostate cancer death by amount, duration, and
      intensity of statin use. Cox proportional hazards regression with postdiagnostic
      statin use as a time-dependent variable. RESULTS: During the median follow-up of
      7.5 yr postdiagnosis 617 men died of prostate cancer. Statin use after diagnosis
      was associated with a decreased risk of prostate cancer death (HR 0.80; 95%
      confidence interval 0.65-0.98). A decreasing risk trend was observed by
      increasing intensity of usage (doses/year). The risk decrease was clearest in men
      managed with androgen deprivation therapy. Prediagnostic statin use was not
      associated with risk of prostate cancer death (HR 0.92; 95% confidence interval
      0.75-1.12). CONCLUSIONS: Decreased risk of prostate cancer death by statin use
      after diagnosis suggests that statins may delay or prevent prostate cancer
      progression. The risk decrease was significant only in men managed with androgen
      deprivation therapy, but statistical power was limited to estimate the
      association in men managed with surgery or radiotherapy. PATIENT SUMMARY: Use of
      statins after prostate cancer diagnosis was associated with a decreased risk of
      prostate cancer death. The risk decrease was dose-dependent and observed
      especially among patients treated with hormone therapy.

PMID- 28753763
TI  - Nuclear Shape and Architecture in Benign Fields Predict Biochemical Recurrence in
      Prostate Cancer Patients Following Radical Prostatectomy: Preliminary Findings.
AB  - BACKGROUND: Gleason scoring represents the standard for diagnosis of prostate
      cancer (PCa) and assessment of prognosis following radical prostatectomy (RP),
      but it does not account for patterns in neighboring normal-appearing benign
      fields that may be predictive of disease recurrence. OBJECTIVE: To investigate
      (1) whether computer-extracted image features within tumor-adjacent benign
      regions on digital pathology images could predict recurrence in PCa patients
      after surgery and (2) whether a tumor plus adjacent benign signature (TABS) could
      better predict recurrence compared with Gleason score or features from benign or
      cancerous regions alone. DESIGN, SETTING, AND PARTICIPANTS: We studied 140 tissue
      microarray cores (0.6mm each) from 70 PCa patients following surgery between 2000
      and 2004 with up to 14 yr of follow-up. Overall, 22 patients experienced
      recurrence (biochemical [prostate-specific antigen], local, or distant recurrence
      and cancer death) and 48 did not. INTERVENTION: RP was performed in all patients.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The top 10 features identified as
      most predictive of recurrence within both the benign and cancerous regions were
      combined into a 10-feature signature (TABS). Computer-extracted nuclear shape and
      architectural features from cancerous regions, adjacent benign fields, and TABS
      were evaluated via random forest classification accuracy and Kaplan-Meier
      survival analysis. RESULTS AND LIMITATIONS: Tumor-adjacent benign field features
      were predictive of recurrence (area under the receiver operating characteristic
      curve [AUC]: 0.72). Tumor-field nuclear shape descriptors and benign-field local
      nuclear arrangement were the predominant features found for TABS (AUC: 0.77).
      Combining TABS with Gleason sum further improved identification of recurrence
      (AUC: 0.81). All experiments were performed using threefold cross-validation
      without independent test set validation. CONCLUSIONS: Computer-extracted nuclear
      features within cancerous and benign regions predict recurrence following RP.
      Furthermore, TABS was shown to provide added value to common predictors including
      Gleason sum and Kattan and Stephenson nomograms. PATIENT SUMMARY: Future studies
      may benefit from evaluation of benign regions proximal to the tumor on surgically
      excised prostate cancer tissue for assessing risk of disease recurrence.

PMID- 28753764
TI  - Contemporary Management of Prostate Cancer Patients Suitable for Active
      Surveillance: A North American Population-based Study.
AB  - BACKGROUND: Active surveillance (AS) is increasingly recognized as a recommended
      treatment option for prostate cancer (PCa) patients with clinically localized,
      low-risk disease; however, previous studies suggested that its utilization is
      uncommon in the United States. OBJECTIVE: We evaluated the nationwide utilization
      rate of AS in the contemporary era. DESIGN, SETTING, AND PARTICIPANTS: We relied
      on the 2010-2011 Surveillance Epidemiology and End Results (SEER) database using
      all 18 SEER-based registries. We identified 9049 patients that fulfilled the
      University of California, San Francisco AS criteria (prostate-specific antigen
      level <10ng/ml, clinical T stage <=2a, Gleason score <=6 [no pattern 4 or 5], and
      percentage of positive biopsy cores <33%). OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Logistic regression analysis tested the relationship between receiving
      local treatment and all available predictors. RESULTS AND LIMITATIONS: Only 32%
      of AS candidates did not receive any active local treatment. This proportion
      varied widely among the SEER-based registries, ranging from 13% to 49% (p<0.001).
      In multivariable analyses, clinical stage T2a (odds ratio [OR]: 1.23; p=0.04) and
      percentage of positive cores (OR: 1.10 for each 2% increase; p<0.001) were
      associated with a higher probability of receiving local treatment. Conversely,
      older age (OR: 0.89 for each 2-yr increase; p<0.001), not being married (OR:
      0.64; p<0.001), and uninsured status (OR: 0.55; p=0.008) were associated with a
      lower probability of receiving active local treatment. The study is limited by
      the fact that SEER does not distinguish among patients undergoing observation,
      AS, watchful waiting, or initial hormonal therapy. CONCLUSIONS: In the United
      States, a considerable proportion of patients suitable for AS receive local
      treatment for PCa. Proportions differ significantly among SEER registries.
      PATIENT SUMMARY: Having more extensive and palpable disease, having medical
      insurance, being married, and being younger are associated with an increased
      probability of receiving local treatment for low-risk prostate cancer.

PMID- 28753765
TI  - Urology Residency Training in Italy: Results of the First National Survey.
AB  - BACKGROUND: Numerous surveys have been performed to determine the competence and
      the confidence of residents. However, there is no data available on the condition
      of Italian residents in urology. OBJECTIVE: To investigate the status of training
      among Italian residents in urology regarding scientific activity and surgical
      exposure. DESIGN, SETTING, AND PARTICIPANTS: A web-based survey that included 445
      residents from all of the 25 Italian Residency Programmes was conducted between
      September 2015 and November 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      The main outcomes were represented by scientific activity, involvement in
      surgical procedures, and overall satisfaction. RESULTS AND LIMITATIONS: In total,
      324 out of 445 (72.8%) residents completed the survey. Overall, 104 (32%)
      residents had not published any scientific manuscripts, 148 (46%) published <=5,
      38 (12%) <=10, 26 (8%) <=15, four (1%) <=20, and four (1%) >20 manuscripts,
      respectively. We did not observe any differences when residents were stratified
      by sex (p=0.5). Stent positioning (45.7%), extracorporeal shock wave lithotripsy
      (30.9%), transurethral resection of bladder tumor (33.0%), hydrocelectomy
      (24.7%), varicocelectomy (17%), ureterolithotripsy (14.5%), and orchiectomy
      (12.3%) were the surgical procedures more frequently performed by residents.
      Overall, 272 residents (84%) expressed a good satisfaction for urology specialty,
      while 178 (54.9%) expressed a good satisfaction for their own residency
      programme. We observed a statistically decreased trend for good satisfaction for
      urology specialty according to the postgraduate year (p=0.02). CONCLUSIONS:
      Italian Urology Residency Programmes feature some heavy limitations regarding
      scientific activity and surgical exposure. Nonetheless, satisfaction rate for
      urology specialty remains high. Further improvements in Residency Programmes
      should be made in order to align our schools to others that are actually more
      challenging. PATIENT SUMMARY: In this web-based survey, Italian residents in
      urology showed limited scientific productivity and low involvement in surgical
      procedures. Satisfaction for urology specialty remains high, demonstrating
      continuous interest in this field of study from residents.

PMID- 28753766
TI  - Human Epidermal Growth Factor Receptor 2 Overexpression in Micropapillary and
      Other Variants of Urothelial Carcinoma.
AB  - BACKGROUND: Human epidermal growth factor receptor 2 (HER2) protein
      overexpression or gene amplification has been shown in urothelial bladder cancer.
      This could be helpful when using targeted anti-HER2 therapy on these tumors.
      OBJECTIVE: To evaluate HER2 immunohistochemical expression in conventional
      urothelial carcinoma (UC), in situ UC, and UC variants primarily in
      micropapillary urothelial carcinoma (MPUC). DESIGN, SETTING, AND PARTICIPANTS:
      The study evaluated 60 MPUC cases; 25 invasive, 20 low-grade noninvasive, and 10
      high-grade noninvasive UC cases; 8 in situ UC cases; and 69 UC variant cases. The
      immunohistochemistry staining was scored according to recommendations of the
      American Society of Clinical Oncology/College of American Pathologists 2013 HER2
      test guideline established for breast cancer and only 3+ staining was considered
      HER2 overexpression. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: HER2
      overexpression was determined by 3+ staining. RESULTS AND LIMITATIONS: 34 of 60
      MPUC cases (56%) showed HER2 overexpression (3+ staining). We observed 3+
      staining HER2 overexpression in nine of 25 conventional invasive UC cases (36%),
      four of eight in situ UC cases (50%), and three of six lipid cell variant cases
      (50%). 3+ staining HER2 overexpression was not seen in eight glandular, six small
      cell, and five sarcomatoid variant cases. HER2 overexpression was negative in the
      20 low-grade noninvasive UC cases but positive in two of the 10 high-grade
      noninvasive UC cases (20%). We observed HER2 overexpression most commonly in MPUC
      cases. We also found HER2 overexpression in conventional invasive and in situ UC
      cases. CONCLUSIONS: Pure in situ UC and conventional invasive UC, especially
      MPUC, could be candidate tumors for treatment with anti-HER2 antibody
      (trastuzumab therapy). PATIENT SUMMARY: Targeted therapy has a limited place in
      treatment of bladder cancer. In this study, human epidermal growth factor
      receptor 2 (HER2) overexpression in bladder carcinomas was evaluated in a large
      number of cases. Anti-HER2 therapy could be used in bladder cancers, as in breast
      and gastric cancers.

PMID- 28753767
TI  - Making Sense of the Statin-Prostate Cancer Relationship: Is It Time for a
      Randomized Controlled Trial?

PMID- 28753768
TI  - A Quality Assessment of Patient-Reported Outcome Measures for Sexual Function in
      Neurologic Patients Using the Consensus-based Standards for the Selection of
      Health Measurement Instruments Checklist: A Systematic Review.
AB  - CONTEXT: Impaired sexual function has a significant effect on quality of life.
      Various patient-reported outcome measures (PROMs) are available to evaluate
      sexual function. The quality of the PROMs to be used for neurologic patients
      remains unknown. OBJECTIVE: To systematically review which validated PROMs are
      available to evaluate sexual function in neurologic patients and to critically
      assess the quality of the validation studies and measurement properties for each
      identified PROM. EVIDENCE ACQUISITION: A systematic review was performed
      according to the Preferred Reporting Items for Systematic Review and Meta
      analysis statement. The included publications were assessed according to the
      Consensus-Based Standards for the Selection of Health Measurement Instruments
      checklist. EVIDENCE SYNTHESIS: Twenty-one studies for PROMs regarding sexual
      function were identified for the following patient groups: spinal cord injury (11
      studies), multiple sclerosis (MS; 6 studies), Parkinson's disease (2 studies),
      traumatic brain injury (1 study), and epilepsy (1 study). The evidence for the
      quality of PROMs was found to be variable, and overall evaluation of measurement
      properties was lacking in 71% of the studies. The measurement error and
      responsiveness were not studied in any of the publications. CONCLUSIONS: Several
      PROMs have been identified to evaluate sexual function in neurologic patients.
      Strong evidence was found only for the Multiple Sclerosis Intimacy and Sexuality
      Questionnaire-15 and Multiple Sclerosis Intimacy and Sexuality Questionnaire-19
      for patients with MS, although evidence was lacking for certain measurement
      properties as well. Future research should focus on identifying relevant PROMs
      and establishing adequate quality for all measurement properties in studies with
      high methodological quality. PATIENT SUMMARY: A quality assessment of patient
      reported outcome measures (PROMs) for sexual function in neurologic patients was
      made. The evidence found for good PROMs was limited. Studies with high
      methodological quality are needed to improve the quality of PROMs to evaluate
      sexual function in neurologic patients.

PMID- 28753769
TI  - Leveraging the Full Potential of Clinical Registries.

PMID- 28753770
TI  - Molecular Characterization of Bladder Cancer in Smokers versus Nonsmokers.
AB  - : Smoking is considered an important risk factor for bladder cancer (BC), yet
      molecular characterization of BC in nonsmokers has not been extensively studied.
      Here, we compare molecular differences between smokers and nonsmokers with BC. BC
      specimens (676) profiled at a Clinical Laboratory Improvement Amendments
      certified laboratory from 2006 to 2014 were retrospectively evaluated for
      molecular differences between smokers and nonsmokers. Protein expression was
      determined with immunohistochemistry. In situ hybridization was used for ERBB2
      (HER2/neu) and EGFR evaluation. Genes were evaluated using Sanger or next
      generation sequencing. Thirty patients were confirmed lifetime nonsmokers (NS)
      and 39 were reformed or current smokers (RCS). There was a trend for increased
      PIK3CA mutations in NS versus RCS (43% vs 11%, p=0.1760), whereas TP53
      alterations were higher in RCS versus NS (63% vs 53%, p=0.6699). EGFR
      amplification was observed more in NS versus RCS (22% vs 11%, p=0.5815), while
      HER2 was amplified only in RCS (23% vs 0%, p=0.05). The molecular differences
      between RCS and NS with BC suggest a different oncogenesis with potentially
      different treatment options. PATIENT SUMMARY: Bladder cancer patients with no
      history of smoking have different molecular characteristics than those with
      smoking history. We found that smokers tend to have higher incidence of HER2
      amplification, whereas nonsmokers seemed to have higher PIK3CA mutation. This
      knowledge provides essential information, which can bear relevance to treatment
      options.

PMID- 28753771
TI  - Quantitative Image Analysis on Histologic Virtual Slides for Prostate Pathology
      Diagnosis, Response to Chemopreventive Agents, and Prognosis.
AB  - A recent investigation follows and expands the field of previous studies on the
      malignancy-associated changes and, above all, adds the missing piece: the role of
      image analysis of normal-looking prostate epithelium in the prediction of
      prognosis. This requires combining and integrating our knowledge of uropathology
      with that of engineering and informatics.

PMID- 28753772
TI  - Occupation and Bladder Cancer Phenotype: Identification of Workplace Patterns
      That Increase the Risk of Advanced Disease Beyond Overall Incidence.
AB  - BACKGROUND: We examined a national data set to determine if workers employed in
      specific occupations develop distinct bladder cancer (BCa) phenotypes. OBJECTIVE:
      To compare the incidence and disease-specific mortality (DSM) of localized and
      advanced BCa in workers with different job titles. DESIGN, SETTING, AND
      PARTICIPANTS: BCa incidence, stage at diagnosis, and DSM in 1.7 million Finnish
      men (13 717 with BCa) and 1.7 million women (4282 with BCa) with annotated
      occupational descriptions. Follow-up was 37 and 43 million person-years,
      respectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The gender-specific
      incidence and BCa DSM within each occupational category was compared with the
      expected number of cases based on the entire Finnish population to generate
      standardized incidence ratios (SIRs) and standard mortality ratios (SMRs).
      RESULTS AND LIMITATIONS: Occupations were found that had significant differences
      in the incidence of localized (SIRloc) and advanced (SIRadv, SMRadv) BCa and DSM.
      Male chemical process workers (SIRloc/SIRadv: 5.19; 95% confidence interval [CI],
      1.73-25.7), male military personnel (SIRloc/SIRadv: 6.4; 95% CI, 1.09-259.0), and
      male public safety workers (SIRloc/SIRadv: 1.77; 95% CI, 1.04-3.23) had
      significantly more localized than advanced tumors. In contrast, miscellaneous
      construction workers had more advanced than localized cancers for both genders
      (male SIRloc/SIRadv: 0.67; 95% CI, 0.53-0.86; female SIRloc/SIRadv: 0.12; 95% CI,
      0.09-0.54). Male chemical process workers had fewer deaths from BCa than expected
      from advanced tumors (SMRadv: 0.32; 95% CI, 0.07-0.94), and miscellaneous
      constructions workers had more deaths from advanced tumors than expected (male
      SMRadv: 1.44; 95% CI, 1.10-1.85; female SMRadv: 3.35; 95% CI, 1.23-7.30).
      Limitations of this study are failure to control accurately for the effects of
      smoking and a lack of specific treatment information. CONCLUSIONS: Occupations
      exist that may differ in their risks for localized and advanced BCa and for DSM.
      PATIENT SUMMARY: Occupations have been identified that may have different
      patterns of bladder cancer than expected. These findings may be explained by
      confounding factors such as exposure to tobacco smoke; however, it could be that
      workers with these job titles are exposed to specific bladder carcinogens.

PMID- 28753773
TI  - Integration of Recurrent Somatic Mutations with Clinical Outcomes: A Pooled
      Analysis of 1049 Patients with Clear Cell Renal Cell Carcinoma.
AB  - BACKGROUND: Analyses of associations between clinicopathologic outcomes and
      recurrent somatic mutations in clear cell renal cell carcinoma (ccRCC) have been
      limited to individual cohorts. OBJECTIVE: To define clinicopathologic
      associations between specific mutations and ccRCC disease characteristics.
      DESIGN, SETTING, AND PARTICIPANTS: DNA sequencing data were pooled from three
      collaborative genomic cohorts (n=754) and our institutional database (n=295). All
      patients had clinical data and identification of somatic mutations from their
      primary tumors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Analysis of gene
      mutations for associations with maximal tumor size (linear regression) and
      pathologic stage (logistic regression). Cancer-specific survival (CSS) and
      recurrence-free survival (RFS) were calculated using competing risks methods.
      Analyses were adjusted for cohort site, and results were adjusted for multiple
      testing (q value). Relevant genes were used in multivariable models that included
      confounding variables and the validated Mayo Clinic Stage, Size, Grade, and
      Necrosis (SSIGN) score. RESULTS AND LIMITATIONS: Association with tumor size was
      found for mutations in BAP1 (q=0.013). No mutations were found to be associated
      with stage after adjusted analysis. Mutations in BAP1 (q=0.004) and TP53
      (q=0.001) were associated with decreased CSS in a multivariable model; only TP53
      (q=0.005) remained significant when SSIGN score was included. SETD2 mutations
      (q=0.047) were associated with decreased RFS in multivariable models, including
      models with SSIGN score. CONCLUSIONS: In >1000 patients with ccRCC, pooled
      analysis and multivariable modeling demonstrated that three mutated genes have
      statistically significant associations with poor clinical outcomes. This included
      the more commonly mutated BAP1 and SETD2 and the less frequently mutated TP53.
      After adjustment for clinical confounders, mutations of TP53 and SETD2 were
      associated with decreased CSS and RFS, respectively. PATIENT SUMMARY: Using
      rigorous statistical methods, this study affirmed that certain mutations in clear
      cell renal cell carcinoma may portend inferior survival and an increased risk of
      recurrence.

PMID- 28753774
TI  - Rationale for Modernising Imaging in Advanced Prostate Cancer.
AB  - CONTEXT: To effectively manage patients with advanced prostate cancer (APC), it
      is essential to have accurate, reproducible, and validated methods for detecting
      and quantifying the burden of bone and soft tissue metastases and for assessing
      their response to therapy. Current standard of care imaging with bone and
      computed tomography (CT) scans have significant limitations for the assessment of
      bone metastases in particular. OBJECTIVE: We aimed to undertake a critical
      comparative review of imaging methods used for diagnosis and disease monitoring
      of metastatic APC from the perspective of their availability and ability to
      assess disease presence, extent, and response of bone and soft tissue disease.
      EVIDENCE ACQUISITION: An expert panel of radiologists, nuclear medicine
      physicians, and medical physicists with the greatest experience of imaging in
      advanced prostate cancer prepared a review of the practicalities, performance,
      merits, and limitations of currently available imaging methods. EVIDENCE
      SYNTHESIS: Meta-analyses showed that positron emission tomography (PET)/CT with
      different radiotracers and whole-body magnetic resonance imaging (WB-MRI) are
      more accurate for bone lesion detection than CT and bone scans (BSs). At a
      patient level, the pooled sensitivities for bone disease by using choline (CH)
      PET/CT, WB-MRI, and BS were 91% (95% confidence interval [CI], 83-96%), 97% (95%
      CI, 91-99%), and 79% (95% CI, 73-83%), respectively. The pooled specificities for
      bone metastases detection using CH-PET/CT, WB-MRI, and BS were 99% (95% CI, 93
      100%), 95% (95% CI, 90-97%), and 82% (95% CI, 78-85%), respectively. The ability
      of PET/CT and WB-MRI to assess therapeutic benefits is promising but has not been
      comprehensively evaluated. There is variability in the cost, availability, and
      quality of PET/CT and WB-MRI. CONCLUSIONS: Standardisation of acquisition,
      interpretation, and reporting of WB-MRI and PET/CT scans is required to assess
      the performance of these techniques in clinical trials of treatment approaches in
      APC. PATIENT SUMMARY: PET/CT and whole-body MRI scans have the potential to
      improve detection and to assess response to treatment of all states of advanced
      prostate cancer. Consensus recommendations on quality standards, interpretation,
      and reporting are needed but will require validation in clinical trials of
      established and new treatment approaches.

PMID- 28753775
TI  - Effectiveness of Adjuvant Chemotherapy After Radical Cystectomy for Locally
      Advanced and/or Pelvic Lymph Node-Positive Muscle-invasive Urothelial Carcinoma
      of the Bladder: A Propensity Score-Weighted Competing Risks Analysis.
AB  - BACKGROUND: The benefit of adjuvant chemotherapy (AC) for muscle-invasive
      urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) is
      controversial. OBJECTIVE: To assess the effectiveness of AC after RC for muscle
      invasive UCB in contemporary European routine practice. DESIGN, SETTING, AND
      PARTICIPANTS: By using a prospectively collected European multicenter database,
      we compared survival outcomes between patients who received AC versus observation
      after RC for locally advanced (pT3/T4) and/or pelvic lymph node-positive (pN+)
      muscle-invasive UCB in 2011. INTERVENTION: AC versus observation after RC.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Inverse probability of treatment
      weighting (IPTW)-adjusted Cox regression and competing risks analyses were
      performed to compare overall survival (OS) as well as cancer-specific and other
      cause mortality between patients who received AC versus observation. RESULTS AND
      LIMITATIONS: Overall, 224 patients who received AC (n = 84) versus observation (n
      = 140) were included. The rate of 3-yr OS in patients who received AC versus
      observation was 62.1% versus 40.9%, respectively (p = 0.014). In IPTW-adjusted
      Cox regression analysis, AC versus observation was associated with an OS benefit
      (hazard ratio: 0.47; 95% confidence interval [CI]: 0.25-0.86; p = 0.014). In IPTW
      adjusted competing risks analysis, AC versus observation was associated with a
      decreased risk of cancer-specific mortality (subhazard ratio: 0.51; 95% CI: 0.26
      0.98; p = 0.044) without any increased risk of other-cause mortality (subhazard
      ratio: 0.48; 95% CI: 0.14-1.60; p = 0.233). Limitations include the relatively
      small sample size as well as the potential presence of unmeasured confounders
      related to the observational study design. CONCLUSIONS: We found that AC versus
      observation was associated with a survival benefit after RC in patients with
      pT3/T4 and/or pN+ UCB. These results should encourage physicians to deliver AC
      and researchers to pursue prospective or large observational investigations.
      PATIENT SUMMARY: Overall survival and cancer-specific survival benefit was found
      in patients who received adjuvant chemotherapy relative to observation after
      radical cystectomy for locally advanced and/or pelvic lymph node-positive bladder
      cancer.

PMID- 28753776
TI  - Consensus Recommendations from the Spanish Germ Cell Cancer Group on the Use of
      High-dose Chemotherapy in Germ Cell Cancer.
AB  - BACKGROUND: High-dose chemotherapy (HDCT) has been studied in several clinical
      scenarios in advanced germ cell cancer (GCC). OBJECTIVE: To establish a clinical
      practice guideline for HDCT use in the treatment of GCC patients. DESIGN,
      SETTING, AND PARTICIPANTS: An expert panel reviewed information available from
      the literature. The panel addressed relevant issues concerning and related to
      HDCT. The guideline was externally reviewed by two international experts. RESULTS
      AND LIMITATIONS: The efficacy of HDCT has been demonstrated in selected GCC
      patients. The most conclusive evidence comes from retrospective analyses that
      need to be interpreted with caution. HDCT can cure a significant proportion of
      heavily treated GCC patients. When indicated, sequential HDCT with regimens
      containing carboplatin and etoposide, as well as peripheral stem-cell support, is
      recommended. There is no conclusive evidence to recommend HDCT as first-line
      therapy. According to a multinational retrospective pooled analysis, HDCT might
      be superior to conventional CT as first salvage treatment in selected patients.
      There is an urgent need for prospective clinical trials addressing the value of
      HDCT in GCC patients who experience failure on first-line cisplatin-based CT. In
      patients who progress on conventional-dose salvage CT, HDCT should be considered.
      Treatment of these patients at experienced centers is strongly recommended.
      CONCLUSIONS: It has been demonstrated that HDCT cures selected GCC patients who
      experience disease progression on conventional rescue regimens. The panel
      recommends the inclusion of GCC patients in randomized clinical trials including
      HDCT. PATIENT SUMMARY: This consensus establishes clinical practice guidelines
      for the use and study of high-dose chemotherapy in patients with germ cell
      cancer.

PMID- 28753777
TI  - Elastic Versus Rigid Image Registration in Magnetic Resonance Imaging-transrectal
      Ultrasound Fusion Prostate Biopsy: A Systematic Review and Meta-analysis.
AB  - CONTEXT: The main difference between the available magnetic resonance imaging
      transrectal ultrasound (MRI-TRUS) fusion platforms for prostate biopsy is the
      method of image registration being either rigid or elastic. As elastic
      registration compensates for possible deformation caused by the introduction of
      an ultrasound probe for example, it is expected that it would perform better than
      rigid registration. OBJECTIVE: The aim of this meta-analysis is to compare rigid
      with elastic registration by calculating the detection odds ratio (OR) for both
      subgroups. The detection OR is defined as the ratio of the odds of detecting
      clinically significant prostate cancer (csPCa) by MRI-TRUS fusion biopsy compared
      with systematic TRUS biopsy. Secondary objectives were the OR for any PCa and the
      OR after pooling both registration techniques. EVIDENCE ACQUISITION: The
      electronic databases PubMed, Embase, and Cochrane were systematically searched
      for relevant studies according to the Preferred Reporting Items for Systematic
      Review and Meta-analysis Statement. Studies comparing MRI-TRUS fusion and
      systematic TRUS-guided biopsies in the same patient were included. The quality
      assessment of included studies was performed using the Quality Assessment of
      Diagnostic Accuracy Studies version 2. EVIDENCE SYNTHESIS: Eleven papers
      describing elastic and 10 describing rigid registration were included. Meta
      analysis showed an OR of csPCa for elastic and rigid registration of 1.45 (95%
      confidence interval [CI]: 1.21-1.73, p<0.0001) and 1.40 (95% CI: 1.13-1.75,
      p=0.002), respectively. No significant difference was seen between the subgroups
      (p=0.83). Pooling subgroups resulted in an OR of 1.43 (95% CI: 1.25-1.63,
      p<0.00001). CONCLUSIONS: No significant difference was identified between rigid
      and elastic registration for MRI-TRUS fusion-guided biopsy in the detection of
      csPCa; however, both techniques detected more csPCa than TRUS-guided biopsy
      alone. PATIENT SUMMARY: We did not identify any significant differences in
      prostate cancer detection between two distinct magnetic resonance imaging
      transrectal ultrasound fusion systems which vary in their method of compensating
      for prostate deformation.

PMID- 28753778
TI  - The Fate of Radical Cystectomy Patients after Hospital Discharge: Understanding
      the Black Box of the Pre-readmission Interval.
AB  - BACKGROUND: Radical cystectomy has one of the highest 30-d hospital readmission
      rates but circumstances leading to readmission remain poorly understood.
      OBJECTIVE: To examine the postdischarge period and better understand hospital
      readmission after radical cystectomy. DESIGN, SETTING, AND PARTICIPANTS: We
      conducted a retrospective cohort study of patients treated with radical
      cystectomy for bladder cancer from 2005 to 2012 using our institutional database.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed patient communication
      with any healthcare system after hospital discharge based on timing, methods, and
      concern types. Logistic regression and Cox proportional-hazards analyses were
      used to compare postdischarge concerns among readmitted and nonreadmitted
      patients. We internally validated the logistic model using a bootstrap resampling
      technique. RESULTS AND LIMITATIONS: One-hundred patients (23%) were readmitted
      within 30 d of index discharge. Readmitted patients were more likely to use the
      emergency department with initial concerns compared with nonreadmitted patients
      (27% vs 1.0%, p<0.001). Patients who took longer to first communicate their
      concerns and who were able to tolerate their symptoms longer had lower odds of
      readmission. Patients who reported infection (adjusted hazard ratio: 2.8, 95%
      confidence interval: 1.4-5.8) and failure to thrive concerns (adjusted hazard
      ratio: 4.4, 95% confidence interval: 2.0-9.3) were more likely to be readmitted
      compared with those who communicated noninfectious wounds and/or urinary
      concerns. CONCLUSIONS: Radical cystectomy patients who contact the health system
      soon after discharge or communicated infectious or failure to thrive symptoms
      (fever, poor oral intake, or vomiting) are more likely to experience readmission
      as opposed to those that endorse pain, constipation, or ostomy issues. Better
      understanding of this pre-readmission interval can optimize postdischarge
      practices. PATIENT SUMMARY: We looked at bladder cancer patients who had surgery
      and the reasons why they were readmitted to hospital. We found patients who had a
      fever or difficulty with eating and maintaining their weight had the highest
      chance of being readmitted.

PMID- 28753779
TI  - Differences in the Molecular Characteristics of Bladder Cancer between Smokers
      and Nonsmokers.

PMID- 28753780
TI  - Validation of a Postoperative Nomogram Predicting Recurrence in Patients with
      Conventional Clear Cell Renal Cell Carcinoma.
AB  - BACKGROUND: Clear cell renal cell carcinoma (RCC) continues to be the most
      commonly diagnosed subtype and is associated with more aggressive behavior than
      papillary and chromophobe RCC. Predicting disease recurrence after surgical
      extirpation is important for counseling and targeting those at high risk for
      adjuvant therapy clinical trials. OBJECTIVE: To validate a postoperative nomogram
      predicting 5-yr recurrence-free probability (RFP) for clinically localized clear
      cell RCC. DESIGN, SETTING, AND PARTICIPANTS: We identified all patients who
      underwent nephrectomy for clinically localized clear cell RCC from 1990 to 2009
      at Memorial Sloan Kettering Cancer Center. After excluding patients with
      bilateral renal masses, familial RCC syndromes, and T3c or T4 tumors due to the
      limited number, 1642 participants were available for analysis. INTERVENTIONS:
      Partial or radical nephrectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Disease recurrence was defined as any new tumor after nephrectomy or kidney
      cancer-specific mortality, whichever occurred first. A postoperative nomogram was
      used to calculate the predicted 5-yr RFP, and these values were compared with the
      actual 5-yr RFP. Nomogram performance was evaluated by concordance index and
      calibration plot. RESULTS AND LIMITATIONS: Median follow-up was 39 mo
      (interquartile range: 14-79 mo), and disease recurrence was observed in 50
      patients. The nomogram concordance index was 0.81. The calibration curve showed
      that the nomogram underestimated the actual 5-yr RFP. We updated the nomogram by
      including the entire patient population, which maintained performance and
      significantly improved calibration. CONCLUSIONS: The updated clear cell RCC
      postoperative nomogram performed well in the combined cohort. Underestimation of
      actual 5-yr RFP by the original nomogram may be due to increased surgeon
      experience and other unknown variables. PATIENT SUMMARY: We updated a valuable
      prediction tool used for assessing the disease recurrence probability after
      nephrectomy for clear cell renal cell carcinoma.

PMID- 28753781
TI  - Prediction of Prostate Cancer: External Validation of the ERSPC Risk Calculator
      in a Contemporary Dutch Clinical Cohort.
AB  - BACKGROUND: The validity of prediction models needs external validation to assess
      their value beyond the original development setting. OBJECTIVE: To report the
      diagnostic accuracy of the European Randomized Study of Screening for Prostate
      Cancer (ERSPC) risk calculator (RC)3 and RC4 in a contemporary Dutch clinical
      cohort. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively identified all men
      who underwent prostate biopsy (PBx) in the Jeroen Bosch Hospital, The
      Netherlands, between 2007 and 2016. Patients were included if they met ERSPC RC
      requirements of age (50-80 yr), prostate-specific antigen (PSA) (0.4-50 ng/ml),
      and prostate volume (10-150ml). The probability of a positive biopsy for prostate
      cancer (PCa) and significant PCa (Gleason score >=7 and/or higher than T2b) were
      calculated and compared with PBx pathology results. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Evaluation was performed by calibration, discrimination,
      and clinical usefulness using calibration plots, area under the receiver
      operating characteristic curves (AUCs), and decision curve analyses (DCAs),
      respectively. RESULTS AND LIMITATIONS: A total of 2270 PBx sessions were eligible
      for final analysis. Discriminative ability of RC3 (AUC) was 0.78 and 0.90 for any
      PCa and significant PCa, respectively. For RC4 the calculated AUCs were 0.62 (any
      PCa) and 0.76 (significant PCa). The calibration plots of RC3 showed good results
      for both any PCa risk and significant PCa risk. In the repeat PBx group, RC4
      tended to underestimate outcomes for PCa and showed moderate calibration for
      significant PCa. DCA showed an overall net benefit compared with PSA and digital
      rectal examination (DRE) alone. Limitations of this study are its retrospective
      single-institution design, retrospectively assessed DRE outcomes, no time
      restrictions between the first and repeat biopsy sessions, and no anterior
      sampling in the repeat PBx protocol. CONCLUSIONS: The ERSPC RCs performed well in
      a contemporary clinical setting. Most pronounced in the biopsy-naive group, both
      RCs should be favoured over a PSA plus DRE-based stratification in the decision
      whether or not to perform PBx. PATIENT SUMMARY: We looked at the ability of the
      existing European Randomized Study of Screening for Prostate Cancer risk
      calculator (RC), using different clinical data to predict the presence of
      prostate cancer in Dutch men. The RC performed well and should be favoured in the
      decision of whether or not to perform prostate biopsies over the conventional
      diagnostic pathway.

PMID- 28753782
TI  - Understanding Mutational Drivers of Risk: An Important Step Toward Personalized
      Care for Patients with Renal Cell Carcinoma.
AB  - The identification of clinically relevant genetic mutations in renal cell
      carcinoma is an important step on the path toward personalized management of this
      disease.

PMID- 28753783
TI  - Gene Expression Profiling of Advanced Penile Squamous Cell Carcinoma Receiving
      Cisplatin-based Chemotherapy Improves Prognostication and Identifies Potential
      Therapeutic Targets.
AB  - : In men with advanced penile squamous cell carcinoma receiving first-line
      chemotherapy, visceral metastases (VM) and Eastern Cooperative Oncology Group
      performance status >=1 are poor prognostic factors for overall survival (OS). We
      hypothesized that tumor gene expression profiling may enhance prognostic
      stratification and identify potential therapeutic targets. In this retrospective
      study, RNA extracted from macrodissected tumors underwent profiling for the
      expression of 738 genes using NanoString. Univariate and multivariate analyses
      assessed the association of genes, VM, and performance status with OS. Tumors
      were available from 25 men who received first-line cisplatin-based chemotherapy.
      In univariate analysis, upregulated MAML2 (p=0.004), KITLG (p<=0.0001), and JAK1
      (p=0.029) genes were associated with poor OS, and upregulated FANCA was
      associated with better OS (p=0.024). In stepwise multivariate analyses, VM
      (hazard ratio=12.75, p=0.0001) and MAML2 (hazard ratio=10.411, p=0.003) were
      associated with poor OS. The presence of none, one, and both of these poor risk
      factors was associated with significantly different median OS of 18.4 mo, 7.2 mo,
      and 2.1 mo, respectively. Unsupervised clustering demonstrated two major
      molecular subtypes with trend for different survivals (p=0.052). Validation of
      results is necessary. PATIENT SUMMARY: The expression of the MAML2 gene in penile
      cancers from men receiving first-line cisplatin-based chemotherapy predicted
      overall survival independent of clinical factors.

PMID- 28753784
TI  - Clinical Case Discussion: Bilateral Synchronous Testicular Cancer and Organ
      sparing Surgery.
AB  - In cases of bilateral synchronous testicular cancer, organ-sparing surgery can be
      performed safely, if appropriate surgical rules are respected and if a stringent
      follow-up protocol is obeyed. If fertility is a concern, a simultaneous TESE
      procedure can be performed.

PMID- 28753785
TI  - YRNA Expression Profiles are Altered in Clear Cell Renal Cell Carcinoma.
AB  - BACKGROUND: Noncoding RNAs play an important role in human carcinogenesis. YRNAs,
      a novel class of noncoding RNAs, have been identified as biomarkers in breast
      cancer patients. OBJECTIVE: To test the hypothesis that YRNA expression is
      dysregulated in clear cell renal cell carcinoma (ccRCC). DESIGN, SETTING, AND
      PARTICIPANTS: We first measured the expression of all known YRNAs (hY1, hY3, hY4,
      and hY5) in a screening cohort (30 ccRCC and 15 normal renal tissues).
      Subsequently, hY3 and hY4 were validated in an independent cohort (88 ccRCC and
      59 normal renal tissues). Finally, hY3 and hY4 levels in serum samples from 30
      ccRCC and 15 control individuals were measured. YRNAs were detected using
      quantitative real-time polymerase chain reaction. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Relative expression values were analyzed using the Mann
      Whitney-U test and Kaplan Meier estimates. RESULTS AND LIMITATIONS: Expression of
      hY3 and hY4 was increased in ccRCC samples compared with normal renal tissue,
      whereas hY1 and hY5 levels were similar. Expression levels of hY4 correlated with
      ccRCC stage and the presence of lymph node metastases. Neither hY3 nor hY4 were
      circulating at different levels in ccRCC patients and control individuals.
      CONCLUSIONS: The expression of hY3 and hY4 is altered in ccRCC and associated
      with advanced disease. PATIENT SUMMARY: In this report we studied the expression
      of noncoding YRNA in clear cell renal cell carcinoma tissue. We observed
      increased hY3 and hY4 expression levels in cancer tissues. However, expression
      levels were not different in the serum of patients with cancer or benign disease.

PMID- 28753786
TI  - Tumor Xenografts of Human Clear Cell Renal Cell Carcinoma But Not Corresponding
      Cell Lines Recapitulate Clinical Response to Sunitinib: Feasibility of Using
      Biopsy Samples.
AB  - BACKGROUND: Parallel development of preclinical models that recapitulate
      treatment response observed in patients is central to the advancement of
      personalized medicine. OBJECTIVE: To evaluate the use of biopsy specimens to
      develop patient-derived xenografts and the use of corresponding cell lines from
      renal cell carcinoma (RCC) tumors for the assessment of histopathology, genomics,
      and treatment response. DESIGN, SETTING, AND PARTICIPANTS: A total of 74 tumor
      specimens from 66 patients with RCC were implanted into immunocompromised NOD
      SCID IL2Rg-/- mice. Four cell lines generated from patients' specimens with clear
      cell pathology were used for comparative studies. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Preclinical models were established and assessed.
      Engraftment rates were analyzed using chi-square testing. Analysis of variance
      (two-way analysis of variance) was conducted to assess tumor growth. RESULTS AND
      LIMITATIONS: Overall, 33 RCC mouse xenograft models were generated with an
      overall engraftment rate of 45% (33 of 74). Tumor biopsies engrafted comparably
      with surgically resected tumors (58% vs 41%; p=0.3). Xenograft tumors and their
      original tumors showed high fidelity in regard to histology, mutation status,
      copy number change, and targeted therapy response. Engraftment rates from
      metastatic tumors were higher but not more significant than primary tumors (54%
      vs 34%; p=0.091). Our engraftment rate using metastases or biopsies was
      comparable with recent reports using resected primary tumors. In stark contrast
      to corresponding cell lines, all tested xenografts recapitulated patients'
      clinical response to sunitinib. CONCLUSIONS: Patient-derived xenograft models can
      be effectively established from tumor biopsies. Preclinical xenograft models but
      not matched cell lines reflected clinical responses to sunitinib. PATIENT
      SUMMARY: Matched patient-derived clear cell renal cell carcinoma xenografts and
      cell lines from responsive and refractory patients treated with sunitinib were
      established and evaluated for pharmacologic response to anti-vascular endothelial
      growth factor treatment. Both models accurately reflected the genetic
      characteristics of original tumors, but only xenografts recapitulated drug
      responses observed in patients. These models could serve as a powerful platform
      for precision medicine.

PMID- 28753787
TI  - In Men with Castration-Resistant Prostate Cancer, Visceral Metastases Predict
      Shorter Overall Survival: What Predicts Visceral Metastases? Results from the
      SEARCH Database.
AB  - BACKGROUND: Although visceral metastases (VMs) are widely recognized to portend
      worse prognoses compared with bone and lymph metastases in men with metastatic
      castration-resistant prostate cancer (mCRPC), little is known about what predicts
      VMs and the extent to which men with VMs do worse. OBJECTIVE: To determine
      whether men with VMs at initial mCRPC diagnosis have worse overall survival (OS)
      and identify predictors of VMs. DESIGN, SETTING, AND PARTICIPANTS: We analyzed
      494 men diagnosed with castration-resistant prostate cancer post-1999 and no
      known metastases from five Veterans Affairs hospitals of the Shared Equal Access
      Regional Cancer Hospital (SEARCH) database who later developed metastases.
      Radiology scans within 30 d of initial metastasis diagnosis were reviewed to
      collect information on bone, visceral, and lymph node metastases. We analyzed the
      236 men who had a computed tomography scan performed. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Predictors of VMs and OS were evaluated using logistic
      regression and Cox models, respectively. RESULTS AND LIMITATIONS: Of the 236
      mCRPC patients, 38 (16%) had VMs. Regarding VMs, 19 patients (50%), 8 patients
      (21%), and 16 patients (42%) had metastases in the liver, lungs, and other
      locations, respectively. VMs were a predictor of OS on crude analysis (hazard
      ratio [HR]: 1.88; 95% confidence interval [CI], 1.30-2.72; p=0.001) and after
      risk adjustment (HR: 1.84; 95% CI, 1.24-2.72; p=0.002). Age, year, treatment
      center, prostate-specific antigen (PSA), and time from CRPC to metastases were
      significant in predicting OS (all p<0.05). None of the variables tested were
      associated with having VMs (all p > 0.09). Prospective studies and larger cohorts
      are needed to validate our findings. CONCLUSIONS: Demographic, tumor, and PSA
      kinetic characteristics were not predictive of having VMs, but VMs predicted
      worse OS. PATIENT SUMMARY: Because patients with VMs have worse overall survival,
      further research is needed to develop better biomarkers and thus diagnose those
      with VMs at earlier stages in their disease course.

PMID- 28753788
TI  - Toward the future of the functional imaging of advanced prostate cancer.
AB  - BS and CT are routinely used to assess the presence of metastases in advanced PCa
      patients. New imaging modalities such as PET and WB-MRI have the potential to
      replace previous imaging techniques allowing to earlier shift to more adequate
      therapies.

PMID- 28753789
TI  - Integrated Phenotypic/Genotypic Analysis of Papillary Renal Cell Carcinoma
      Subtypes: Identification of Prognostic Markers, Cancer-related Pathways, and
      Implications for Therapy.
AB  - BACKGROUND: Two histologic subtypes are recognized for papillary renal cell
      carcinoma (PRCC). Studies have shown that the subtypes differ in characteristic
      genetic alterations and clinical behavior. Clinically, the subtypes are managed
      similarly. OBJECTIVES: To analyze the biological differences between the two PRCC
      histological subtypes, in order to further guide their clinical management.
      DESIGN, SETTING, AND PARTICIPANTS: PRCC cohort consisting of 317 patients from
      the Cancer Genome Atlas database and our institution. Patients were stratified
      according to histologic criteria as type 1, type 2, or not otherwise specified
      (NOS). Gene and miRNA expression data for the cohort were examined via
      unsupervised and supervised clustering. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Significant molecular signatures for each subtype were used to unravel
      the implicated molecular pathways via bioinformatics analysis. Survival was
      compared between the subtypes. Newly discovered biomarkers were used to further
      stratify survival of patients in the NOS category. RESULTS AND LIMITATIONS: Tumor
      genotyping revealed two distinct PRCC subtypes. The top molecular pathways
      enriched in PRCC1 were WNT, Hedgehog, and Notch signaling (p=0.001-0.01);
      highlighting an embryonic developmental theme to the pathogenesis of this
      subtype. PRCC2 showed enrichment in the mTOR, VEGF (p=7.49E-09) and HIF (p=7.63E
      05) signaling pathways. Overall survival and disease-free survival significantly
      differed between the types. ABCC2 expression was identified as a significant
      prognostic biomarker for the NOS group in univariate (log rank p<0.0001; hazard
      ratio [HR] >11.63) and multivariate analysis (p=0.003; HR >2.12). ABCC2
      expression and its effect on survival should be further validated at the protein
      level. CONCLUSIONS: The classical PRCC types 1 and 2 have two distinct genotypes.
      We unraveled pathways that indicate that the two types could potentially respond
      differently to current therapies. We also identified biomarkers that stratify
      tumors within the PRCC NOS category into prognostic subgroups. Our findings
      highlight the need for molecular markers to accurately subtype PRCC and guide
      clinical management. PATIENT SUMMARY: The two types of papillary renal cancer are
      treated similarly. We show that the two types have a different genetic makeup,
      and hence they should be considered two different tumors. There is a different
      biology underlying each tumor type that can potentially affect the way they
      respond to treatment. We uncovered genes that can be tested for to guide therapy
      in some problematic cases for which it hard to define the tumor type.

PMID- 28753790
TI  - Positive Pelvic Lymph Nodes in Prostate Cancer Harbor Immune Suppressor Cells To
      Impair Tumor-reactive T Cells.
AB  - : The impact of prostate cancer (PCa) metastases on pelvic lymph nodes in local
      antitumor immunity remains unknown. We prospectively enrolled ten hormone therapy
      naive men undergoing salvage pelvic lymph node dissection (sPLND) and analyzed
      their peripheral blood (PB) and positive pelvic lymph nodes (PPLNs) with PCa
      metastases for tumor-reactive CD8+ T cells and myeloid-derived suppressor cells
      (MDSCs) using flow cytometry. MDSCs were stratified into CD14+ monocytic and CD14
      granulocytic types. PD-L1/2 expression was also analyzed for MDSCs. Relative to
      PB, tumor-reactive CD8+ T cells accumulated in PPLNs (p<0.01) yet had decreased
      proliferation, with low Ki67 expression (p<0.05). Both CD14+ monocytic and CD14-
      granulocytic MDSCs were found in PPLNs, but there was an increase in the
      proportion of CD8+ T cells in PPLNs compared to PB (p<0.01). The granulocytic
      MDSCs exhibited a high degree of immunosuppressive activity (as evidenced by high
      pSTAT3 levels) and high levels of B7-H1 (PD-L1) and B7-DC (PD-L2) expression.
      Thus, granulocytic MDSCs probably suppress tumor-reactive CD8+ T-cells in PPLNs
      and exhibit high expression of immune checkpoint molecules in PCa nodal
      metastases. The data suggest a relative immunosuppressive state in PPLNs. This
      provides a biologic rationale for sPLND beyond just tumor debulking, and calls
      for further investigation of immune checkpoint blockade. PATIENT SUMMARY:
      Prostate cancer metastases to lymph nodes may involve immunosuppressive cells
      that evade antitumor T-cells and create a relatively immunosuppressed state. This
      provides a rationale for treatment of such lymph nodes and/or for potential
      immunotherapy.

PMID- 28753791
TI  - A Prospective Observational Study for Assessment and Outcome Association of
      Circulating Endothelial Cells in Clear Cell Renal Cell Carcinoma Patients Who
      Show Initial Benefit from First-line Treatment. The CIRCLES (CIRCuLating
      Endothelial cellS) Study (SOGUG-CEC-2011-01).
AB  - BACKGROUND: Markers able to predict the response to antiangiogenics in metastatic
      clear cell renal cell carcinoma (ccRCC) are not available. The development of new
      treatment options like immunotherapy are reaching the clinic; therefore,
      predictors of benefit from these different available treatments are increasingly
      needed. OBJECTIVE: In this study, we prospectively assessed the association of
      circulating endothelial cells (CECs) in peripheral blood with long-term benefit
      from first-line treatment in ccRCC. DESIGN, SETTING, AND PARTICIPANTS: A
      prospective observational study was designed involving 13 institutions of the
      Spanish Oncology Genitourinary Group. Adult patients diagnosed with advanced
      ccRCC who had achieved response or disease stabilization after 3 mo on first-line
      therapy were eligible. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: CECs were
      isolated from peripheral blood, captured with ferrofluids coated with monoclonal
      antibodies directed against the CD146 antigen, and assessed centrally with an
      automated standardized system. CECs were defined as 4',6-diamidino-2
      phenylindole+, CD105+, and CD45-. Blood samples were systematically taken every 6
      wk for 15 mo or until tumor progression, whichever occurred first. Clinical data
      were externally monitored at all centers. RESULTS AND LIMITATIONS: From August 9,
      2011, to January 17, 2013, 75 patients were enrolled in the study. Patients with
      baseline CECs above the median showed a significantly longer progression-free
      survival than those with low CECs (22.2 mo vs 12.2 mo) with a hazard ratio of 2.5
      (95% confidence interval: 1.2-5.3, p=0.016). There was no difference between CEC
      levels at baseline and at tumor progression (medians of 50 CECs/4ml and 52
      CECs/4ml, respectively). CONCLUSIONS: Under antiangiogenic treatment, the
      detection of higher CEC levels is associated with clinical benefit in terms of
      progression-free survival in ccRCC. PATIENT SUMMARY: Antiangiogenics are the
      cornerstone of treatment in kidney cancer. Since they target endothelial rather
      than tumor cells, we studied the correlation between levels of circulating
      endothelial cells in peripheral blood and long-term benefit in patients on
      antiangiogenic therapy. Higher levels were associated with long-term benefit,
      suggesting that this determination could help to separate best responders from
      those who could require a more intensive approach.

PMID- 28753792
TI  - Interrogating Metastatic Prostate Cancer Treatment Switch Decisions: A Multi
      institutional Survey.
AB  - BACKGROUND: Evaluation of responses to treatment for metastatic castration
      resistant prostate cancer (mCRPC) remains challenging. Consensus criteria based
      on prostate-specific antigen (PSA) and clinical and radiologic biomarkers are
      inconsistently utilized. Circulating tumor cell (CTC) counts can inform prognosis
      and response, but are not routinely used. OBJECTIVE: To evaluate the use of
      biomarkers and trends in clinical decision-making in current mCRPC treatment.
      DESIGN, SETTING, AND PARTICIPANTS: A 23-part online questionnaire was completed
      by physicians treating mCRPC. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Results
      are presented as the proportion (%) of physicians responding to each of the
      options. We used chi2 and Fisher's tests to compare differences. RESULTS AND
      LIMITATIONS: A total of 118 physicians (22.1%) responded. Of these, 69.4% treated
      >=50 mCRPC patients/year. More physicians administered four or fewer courses of
      cabazitaxel (27.9%) than for docetaxel (10.4%), with no significant difference in
      the number of courses between bone-only disease and Response Evaluation Criteria
      in Solid Tumours (RECIST)-evaluable disease. Some 74.5% of respondents considered
      current biomarkers useful for monitoring disease, but only 39.6% used the
      Prostate Cancer Working Group (PCWG2) criteria in clinical practice. PSA was
      considered an important biomarker by 55.7%, but only 41.4% discarded changes in
      PSA before 12 wk, and only 39.4% were able to identify bone-scan progression
      according to PCWG2. The vast majority of physicians (90.5%) considered clinical
      progression to be important for switching treatment. The proportion considering
      biomarkers important was 71.6% for RECIST, 47.4% for bone scans, 23.2% for CTCs,
      and 21.1% for PSA. Although 53.1% acknowledged that baseline CTC counts are
      prognostic, only 33.7% would use CTC changes alone to switch treatment in
      patients with bone-only disease. The main challenges in using CTC counts were
      access to CTC technology (84.7%), cost (74.5%), and uncertainty over utility as a
      response indicator (58.2%). CONCLUSIONS: A significant proportion of physicians
      discontinue treatment for mCRPC before 12 wk, raising concerns about inadequate
      response assessment. Many physicians find current biomarkers useful, but most
      rely on symptoms to drive treatment switch decisions, suggesting there is a need
      for more precise biomarkers. PATIENT SUMMARY: In this report we analyse the
      results of a questionnaire evaluating tools for clinical decision-making
      completed by 118 prostate cancer specialists. We found that most physicians
      favour clinical progression over prostate-specific antigen or imaging, and that
      criteria established by the Prostate Cancer Working Group are not widely used.

PMID- 28753793
TI  - MicroRNAs in Serum Exosomes as Potential Biomarkers in Clear-cell Renal Cell
      Carcinoma.
AB  - BACKGROUND: Circulating microRNAs (miRNAs) in exosomes are emerging as clinically
      useful tools for cancer detection. However, little is known about their
      diagnostic impact in clear-cell renal cell carcinoma (ccRCC). OBJECTIVE: To
      investigate whether miRNAs in serum exosomes can serve as biomarkers in ccRCC.
      DESIGN, SETTING, AND PARTICIPANTS: Serum samples were obtained from 82 patients
      with ccRCC and 80 healthy volunteers. Exosomes were extracted and purified to
      selectively capture exosomes positive for tumor-associated epithelial cell
      adhesion molecule (EpCAM) via a magnetic bead technique. Total RNA was extracted
      and expression levels of miR-210, miR-1233, and miR-15a miRNAs were quantified
      and normalized to U6 levels. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Expression levels were compared using a Mann-Whitney U-test, Friedman test, or
      Wilcoxon test. Receiver operating characteristic (ROC) curves were plotted to
      assess the diagnostic value of exosomal miRNAs for differentiation between ccRCC
      patients and controls. RESULTS AND LIMITATIONS: Expression levels of exosomal miR
      210 and miR-1233 were significantly higher in ccRCC patients than in healthy
      individuals (both p<0.01). No significant difference was observed for exosomal
      miR-15a. Exosomal miR-210 and miR-1233 expression levels in different TNM stages
      were significantly higher than in the controls (all p<0.01). Exosomal miR-210 and
      miR-1233 expression levels were significantly lower in postoperative than in
      preoperative samples (both p<0.01). ROC analysis demonstrated that exosomal
      expression levels distinguished ccRCC patients from healthy individuals with 70%
      sensitivity and 62.2% specificity for miR-210, and 81% sensitivity and 76%
      specificity for miR-1233. The retrospective design and lack of other tumor
      subtypes are limitations of the study. CONCLUSIONS: Serum exosomal miRNAs might
      represent potential diagnostic biomarkers in ccRCC in the future. PATIENT
      SUMMARY: Circulating levels of exosomal microRNAs miR-210 and miR-1233 have
      potential as biomarkers for diagnostic and monitoring purposes in renal cancer in
      the future. These molecules can be measured in serum in so-called liquid biopsy.

PMID- 28753794
TI  - Differences in Trial and Real-world Populations in the Dutch Castration-resistant
      Prostate Cancer Registry.
AB  - BACKGROUND: Trials in castration-resistant prostate cancer (CRPC) treatment have
      shown improved outcomes, including survival. However, as trial populations are
      selected, results may not be representative for the real-world population. The
      aim of this study was to assess the differences between patients treated in a
      clinical trial versus standard care during the course of CRPC in a real-world
      CRPC population. DESIGN, SETTING, AND PARTICIPANTS: Castration-resistant Prostate
      Cancer Registry is a population-based, observational, retrospective registry.
      CRPC patients from 20 hospitals in the Netherlands have been included from 2010
      to 2013. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics,
      systemic treatment, and overall survival were the main outcomes. Descriptive
      statistics, multivariate Cox regression, and multiple imputations with the Monte
      Carlo Markov Chain method were used. RESULTS AND LIMITATIONS: In total, 1524
      patients were enrolled of which 203 patients had participated in trials at any
      time. The median follow-up period was 23 mo. Patients in the trial group were
      significantly younger and had less comorbidities. Docetaxel treatment was more
      frequently used in trial patients (85% vs 40%). Despite an observed unadjusted
      median overall survival difference of 35 mo versus 24 mo between the trial and
      standard care group, this difference was not retained after adjustment for
      baseline characteristics and treatment effect. CONCLUSIONS: At CRPC diagnosis,
      the baseline characteristics of the patients who had been enrolled in trials
      notably differed from patients who received standard treatment options only. The
      survival difference between the trial and standard care group could be explained
      by baseline differences and treatment effects. These results indicate that trial
      results cannot easily be translated to real-world practice. PATIENT SUMMARY: We
      observed that patients treated in clinical trials differed from patients who were
      not. We concluded that this may lead to differential treatment and survival.
      Caution is warranted when real-world outcomes are compared with trial results.

PMID- 28753795
TI  - Postoperative 30-day Mortality Rates for Kidney Cancer Are Dependent on Hospital
      Surgical Volume: Results from a Norwegian Population-based Study.
AB  - BACKGROUND: To improve cancer care in Norway, the government introduced surgical
      volume requirements for hospitals in 2015. To treat kidney cancer (KC) in Norway,
      the lower limit is 20 surgical procedures per year. OBJECTIVES: To compare the
      impact of hospital volume on outcome with regard to 30-d mortality (TDM)
      following KC surgery. DESIGN, SETTING, AND PARTICIPANTS: We identified all KC
      patients from the Cancer Registry of Norway diagnosed during 2008-2013 whose
      surgical treatment involved partial or radical nephrectomy. Hospitals were
      divided into three volume groups: low (LVH), intermediate (IVH), and high (HVH)
      volume. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with outcome
      were analysed using multivariate logistic regression. RESULTS AND LIMITATIONS: In
      total, 3273 patients were identified. The TDM rate was 0.89% overall, 0.73% for
      localised KC, and 2.6% for metastatic KC. The mean (median, interquartile range)
      numbers of procedures for LVH, IVH and HVH were 5.2 /yr (3, 1.3-8.7), 27 /yr (26,
      23-30) and 53 /yr (53, 48-58), with TDM rates of 2.2%, 0.83%, and 0.39%,
      respectively (p=0.001). In a multivariate logistic regression model, tumour
      stage, age, and hospital volume remained independent TDM predictors. The odds
      ratio for TDM was 4.98 (confidence interval 1.72-14.4) for LVH compared to HVH
      (p=0.003). Study limitations include a lack of data for surgical complications
      and other possible confounders. CONCLUSIONS: TDM is associated with age, stage,
      and hospital volume. The study supports the new regulation for hospital volume
      introduced in Norway. PATIENT SUMMARY: The risk of dying within 30 d following
      kidney cancer surgery is low. Advanced disease and older age are risk factors for
      higher mortality. In this study, we also showed that more patients die within 30
      d in hospitals performing fewer operations per year than in hospitals performing
      many operations.

PMID- 28753796
TI  - Serum Concentrations of Sex Hormone-binding Globulin Vary Widely in Younger and
      Older Men: Clinical Data from a Men's Health Practice.
AB  - BACKGROUND: The testosterone (T) status of a man is influenced by serum
      concentrations of sex hormone-binding globulin (SHBG). Specifically, tight
      binding of T to SHBG is believed to render the SHBG-bound T fraction biologically
      unavailable, meaning that interpretation of T levels in the clinical setting
      depends in part on knowledge of SHBG concentrations. Although SHBG levels have
      been reported in population studies, there is scant information for men
      presenting with clinical symptoms. OBJECTIVE: To report SHBG values for a large
      cohort of men presenting to a men's health center. DESIGN, SETTING, AND
      PARTICIPANTS: Medical records were reviewed for 1000 consecutive patients seen at
      our center with a reported SHBG value. SHBG concentrations were measured by a
      national clinical laboratory using an immunoassay run on a Beckman Coulter DXi
      system. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were age
      stratified and data were plotted in the form of comparative histograms. RESULTS
      AND LIMITATIONS: The mean age (+/-standard deviation) of the total cohort was
      53.5+/-13.5 yr (range 17-91). The mean SHBG was 31.8+/-15.2nmol/l (range 6-109),
      with a nearly 20-fold difference from the lowest to the highest values. SHBG was
      >60nmol/l in 5.6% of the men. Patients were stratified according to age. A total
      of 535 patients were <=54 yr old. In this younger cohort, the mean age was
      40.52+/-7.9 yr (range 17-54) and mean SHBG was 27.7+/-13.3nmol/l (range 6-88),
      and 2.2% of patients had SHBG >60nmol/l. A total of 465 patients were >=55 yr
      old. In this older cohort, the mean age was 64.8+/-7.23 yr (range 55-91) and mean
      SHBG was 36.6+/-15.8 nmol/l (range 11-109), and 9% of patients had SHBG >60
      nmol/l. Mean SHBG was significantly higher in the older group (p<0.001).
      CONCLUSIONS: A remarkably wide distribution of SHBG concentrations was observed
      in a clinical population of men presenting to a men's health center, among both
      younger and older men. Since SHBG concentrations greatly influence test results
      for hormones that bind to SHBG, recognition of this large interindividual
      variability should be considered in the clinical interpretation of these hormone
      results, particularly for T. Routine SHBG testing should be considered for men
      suspected of T deficiency. PATIENT SUMMARY: Sex hormone-binding globulin (SHBG)
      levels vary widely among both older and younger men. This may impact the
      interpretation of test results for hormones that bind to SHBG, such as
      testosterone, since the portion that binds to SHBG is believed to not be
      biologically available.

PMID- 28753797
TI  - [18F]-DCFPyL Positron Emission Tomography/Magnetic Resonance Imaging for
      Localization of Dominant Intraprostatic Foci: First Experience.
AB  - : An ongoing prospective study is acquiring preoperative imaging data for men
      with prostate cancer (PCa) using the molecular imaging agent [18F]-DCFPyL
      targeted against prostate-specific membrane antigen (PSMA). To date, six men (of
      a planned accrual of 24) with clinically localized, biopsy-proven PCa have
      undergone preoperative [18F]-DCFPyL positron emission tomography (PET) imaging
      and multiparametric magnetic resonance imaging acquired using a hybrid PET/MRI
      system. Lesions identified by [18F]-DCFPyL uptake on PET/MRI were characterized
      in terms of maximum standardized uptake value (SUVmax) and volume using a
      boundary threshold of 40% SUVmax. Following surgery, all prostatectomy specimens
      were processed using a whole-mount technique for accurate deformable co
      registration and correlation with PCa foci defined on digitized pathology images.
      Well-defined intraprostatic dominant lesions were identified by [18F]-DCFPyL
      PET/MRI (mean SUVmax 11.4+/-8.25; mean volume 2.2+/-2.4cm3) in all six men. Co
      registered digitized whole-mount pathology for the first case revealed that
      intense [18F]-DCFPyL uptake (SUVmax 27+/-1.1cm3) and multiparametric MRI changes
      (Prostate Imaging Reporting and Data System score of 4) were highly correlated
      with a 0.5-cm3 dominant (largest) lesion with Gleason pattern 4 PCa in the right
      mid peripheral zone. A smaller focus (0.01cm3) of lower-grade PCa (Gleason
      pattern 3) had much lower uptake (SUV 2.7). These early prospective data show
      that dominant intraprostatic lesions could be identified in all six men using
      [18F]-DCFPyL as an imaging probe. Trial accrual will continue to quantify in
      terms of spatial concordance the ability of [18F]-DCFPyL to identify the location
      and characterize the grade of intraprostatic cancer foci in clinically localized
      PCa. PATIENT SUMMARY: Positron emission tomography using a novel probe called
      [18F]-DCFPyL directed against the prostate-specific membrane antigen protein was
      able to identify locations of prostate cancer in the prostate glands of men
      undergoing imaging before surgery. In the future, such imaging may allow better
      targeting of treatment to the portion of the prostate containing the most
      aggressive components of cancer rather than treating the whole prostate in a
      uniform fashion.

PMID- 28753798
TI  - Selection Effects May Explain Smoking-related Outcome Differences After Radical
      Cystectomy.
AB  - The impact of smoking on mortality among patients with bladder cancer is subject
      to controversy. We investigated 1000 patients who consecutively underwent radical
      cystectomy between 1993 and 2013. Proportional hazards models for competing risks
      were used to study the combined effects of variables on mortality. Compared to
      nonsmokers, current smokers were more frequently male (35.7% vs 12.0%, p<0.0001),
      younger (63.5 vs 70.5 yr, p<0.0001), had a lower body mass index (26.2 vs
      27.1kg/m2, p<0.0001), and suffered less frequently from cardiac insufficiency
      (12.7% vs 19.3%, p=0.0129). Among current smokers there was a trend towards lower
      bladder cancer mortality and higher competing mortality in comparison to
      nonsmokers. On multivariable analysis, current smoking was not a predictor of
      bladder cancer mortality (hazard ratio [HR] in the full model 0.76; p=0.0687) but
      was a predictor of competing mortality (HR in the optimal model 1.62; p=0.0044).
      In conclusion, this study did not confirm adverse bladder cancer-related outcome
      among current smokers after radical cystectomy. With a younger mean age and a
      male predominance, there was a trend towards lower bladder cancer mortality
      current smokers that was eventually neutralized by higher competing mortality,
      illustrating that selection effects may explain some smoking-related outcome
      differences after radical cystectomy. The single-center design is a study
      limitation. PATIENT SUMMARY: Current smokers are not at higher risk of bladder
      cancer after radical cystectomy but have a higher risk of competing mortality.

PMID- 28753799
TI  - A Novel Urine-Based Assay for Bladder Cancer Diagnosis: Multi-Institutional
      Validation Study.
AB  - BACKGROUND: CellDetect is a unique histochemical stain enabling color and
      morphological discrimination between malignant and benign cells based on
      differences in metabolic signature. OBJECTIVE: The objective of the present study
      was to validate the performance of this assay in a controlled, blinded,
      multicenter study. DESIGN, SETTING, AND PARTICIPANTS: The study, conducted in
      nine hospitals, included patients with documented history of bladder cancer,
      monitored for urothelial carcinoma (UCC) or scheduled for bladder cancer surgery.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cystoscopy and/or biopsy were used
      as a reference standard to determine sensitivity and specificity. Smears were
      stained by CellDetect and interpreted by two cytologists blinded to the patient's
      final diagnosis. The findings were compared with those of standard urine cytology
      and BTA stat. RESULTS AND LIMITATIONS: Two hundred and seventeen voided urine
      specimens were included. Ninety-six (44%) were positive by histology and 121
      (56%) were negative by either cystoscopy or histology. The overall sensitivity of
      CellDetect was 84%. Notably, the sensitivity for detecting low-grade nonmuscle
      invasive bladder cancer tumors was greater than this of BTA stat (78% vs 54%) and
      more than two-fold higher compared with standard cytology (33%, p <= 0.05). The
      specificity was 84% in patients undergoing routine surveillance by cystoscopy. At
      a median follow-up of 9 mo, 21% of the patients with positive CellDetect and
      negative reference standard developed UCC, which was significantly higher
      compared with the 5% of the true negative cases. Limitations include the lack of
      instrumental urine samples and the lack of patients with nongenitourinary cancers
      in the study population. CONCLUSIONS: This study validates the performance of
      CellDetect as a urine-based assay to identify UCC in patients with history of
      bladder cancer. The high sensitivity was maintained across all cancer grades and
      stages without compromising the assay specificity. Further studies are required
      to test whether this novel stain can be incorporated in routine bladder cancer
      surveillance as a noninvasive alternative to cystoscopy. PATIENT SUMMARY:
      Surveillance of bladder cancer requires frequent invasive procedures. In the
      present study, we validate the ability of a novel biomarker to accurately
      identify early-stage tumors in urine specimens for the noninvasive monitoring of
      patients with history of bladder cancer.

PMID- 28753800
TI  - Correlation Between Confocal Laser Endomicroscopy (Cellvizio(r)) and Histological
      Grading of Upper Tract Urothelial Carcinoma: A Step Forward for a Better
      Selection of Patients Suitable for Conservative Management.
AB  - BACKGROUND: Despite the recent growing interest in the conservative management of
      upper tract urothelial carcinoma (UTUC), the diagnostic process is still a
      challenge for the risk of tumor undergrading. Real-time confocal laser
      endomicroscopy (CLE) provides in vivo microscopic images of tissues using a low
      energy laser light source. OBJECTIVE: To describe our initial experience with CLE
      for the real-time characterization of UTUC. DESIGN, SETTING, AND PARTICIPANTS:
      Fourteen flexible ureteroscopies (f-URS) were performed at our center with CLE
      for UTUC. Lesions were preoperatively identified at computed tomography
      intravenous urography. Cellvizio system was used during f-URS to perform CLE on
      the targeted lesions. Biopsies were then performed. INTERVENTION: f-URS with CLE.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Surgeon's CLE readings (low
      grade/high-grade/carcinoma in situ [CIS]) were documented in the operation notes.
      A dedicated genitourinary pathologist-blinded to the surgeon reading-examined all
      specimens. A third person collected prospectively the CLE readings and the
      histopathological reports. Cohen's Kappa analysis was performed to test
      interobserver agreement. RESULTS AND LIMITATIONS: The mean diameter of tumors at
      computed tomography scan was 26mm (range, 5-50mm). In eight patients, CLE allowed
      to obtain images compatible with low-grade UTUC, in five patients with high-grade
      UTUC, and in one case with CIS. We found correspondence between the CLE images
      and the final histopathological results in seven out of seven cases of low-grade
      UTUC (100%), in five out of six cases of high-grade UTUC (83%), and in one out of
      one case of CIS (100%). Substantial agreement was found at interobserver
      agreement (k=0.64) between CLE and histological reading. No complications and/or
      limitations related to the use of CLE were recorded. CONCLUSIONS: CLE is a
      promising new technology in providing a reliable real-time histological
      characterization of UTUC lesions. Ideal targets might be UTUC patients
      potentially candidates for conservative management. PATIENT SUMMARY: We believe
      that a conservative treatment for low-grade upper tract urothelial carcinoma is
      an option that must be considered. The diagnostic process is still lacking of
      accurate tools. In this study, we find that confocal laser endomicroscopy, using
      the Cellvizio system, seems to help the clinician to have a real-time
      histological characterization of upper tract urothelial carcinoma lesions. This
      could better select patients for a conservative treatment.

PMID- 28753801
TI  - Age >=40 Years Is Associated with Adverse Outcome in Metastatic Germ Cell Cancer
      Despite Appropriate Intended Chemotherapy.
AB  - BACKGROUND: Age >=40 yr is associated with poorer testicular cancer outcomes in
      population-based studies. OBJECTIVE: To assess the association between age (>=40
      yr) and outcomes among men with germ cell tumors (GCTs) in a large hospital
      registry. DESIGN, SETTING, AND PARTICIPANTS: Electronic medical records for 1095
      GCT patients treated at Dana-Farber Cancer Institute between 1997 and 2013 were
      reviewed. Information regarding histology, stage, treatment, and patient
      characteristics was obtained. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Using logistic regression analysis and Cox proportional hazards regression, we
      investigated the association between age and treatment and risk of relapse and
      GCT-specific death for men with GCT. RESULTS AND LIMITATIONS: At diagnosis, 26%
      of men (n=283/1095) were >=40 yr. Among the 610 men with clinical stage 1 (CS1)
      disease, age >=40 yr was not associated with a higher risk of CS1 relapse (hazard
      ratio [HR] 1.19, 95% confidence interval [CI] 0.74-1.92). There were 603 men with
      metastatic disease (CS1 at diagnosis with subsequent relapse or metastasis at
      diagnosis); after adjusting for stage and histology, men >=40 yr were more likely
      to receive etoposide and cisplatin chemotherapy compared to bleomycin, etoposide,
      and cisplatin as their primary treatment (odds ratio 2.40, 95% CI 1.14-5.05).
      Salvage therapy also differed by age. In the multivariable model, men >=40 yr
      with metastatic GCT had a higher risk of relapse (HR 1.58, 95% CI 1.02-2.46)
      after primary treatment and death from GCT (HR 2.31, 95% CI 1.29-4.15). The study
      limitations include incomplete data on medical comorbidities and possible
      subsequent dose modifications. CONCLUSIONS: Men aged >=40 yr with metastatic GCT
      have poorer outcomes, even after accounting for different intended treatment
      patterns. PATIENT SUMMARY: In this study we looked at the outcome for testicular
      cancer in more than 1000 patients treated at a single institution in the USA. We
      found that the treatment for metastatic disease differed between older (>=40 yr)
      and younger patients. Furthermore, outcomes for older patients (>=40 yr) were
      worse than for younger men.

PMID- 28753802
TI  - Oncologic Outcomes After Robot-assisted Radical Prostatectomy: A Large European
      Single-centre Cohort with Median 10-Year Follow-up.
AB  - BACKGROUND: Robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa)
      treatment has been widely adopted with limited evidence for long-term (>5 yr)
      oncologic efficacy. OBJECTIVE: To evaluate long-term oncologic outcomes following
      RARP. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 885 patients
      who underwent RARP as monotherapy for PCa between 2002 and 2006 in a single
      European centre and followed up until 2016. INTERVENTION: RARP as monotherapy.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical recurrence (BCR)-free
      survival (BCRFS), salvage therapy (ST)-free survival (STFS), prostate cancer
      specific survival (CSS), and overall survival (OS) were estimated using the
      Kaplan-Meier method, and event-time distributions were compared using the log
      rank test. Variables predictive of BCR and ST were identified using Cox
      proportional hazards models. RESULTS AND LIMITATIONS: We identified 167 BCRs, 110
      STs, 16 PCa-related deaths, and 51 deaths from other/unknown causes. BCRFS, STFS,
      CSS, and OS rates were 81.8%, 87.5%, 98.5%, and 93.0%, respectively, at median
      follow-up of 10.5 yr. On multivariable analysis, the strongest independent
      predictors of both BCR and ST were preoperative Gleason score, pathological T
      stage, positive surgical margins (PSMs), and preoperative prostate-specific
      antigen. PSM >3mm/multifocal but not <=3mm independently affected the risk of
      both BCR and ST. Study limitations include a lack of centralised histopathologic
      reporting, lymph node and post-operative tumour volume data in a historical
      cohort, and patient-reported outcomes. CONCLUSIONS: RARP appears to confer
      effective long-term oncologic efficacy. The risk of BCR or ST is unaffected by
      <=3mm PSM, but further follow-up is required to determine any impact on CSS.
      PATIENT SUMMARY: Robot-assisted surgery for prostate cancer is effective 10 yr
      after treatment. Very small (<3mm) amounts of cancer at the cut edge of the
      prostate do not appear to impact on recurrence risk and the need for additional
      treatment, but it is not yet known whether this affects the risk of death from
      prostate cancer.

PMID- 28753803
TI  - The Stockholm-3 (STHLM3) Model can Improve Prostate Cancer Diagnostics in Men
      Aged 50-69 yr Compared with Current Prostate Cancer Testing.
AB  - : Prostate cancer screening is associated with low specificity, unnecessary
      biopsies, and overdiagnosis. We have previously shown that the Stockholm-3 model
      (S3M) can reduce biopsies compared with using prostate-specific antigen (PSA)
      >=3ng/ml as an indication for biopsy. Urologists in today's current prostate
      cancer testing (CPT) have access to numerous variables in addition to PSA (eg,
      age, ethnicity, family history, free PSA, PSA velocity, digital rectal
      examination, and prostate volume) to support biopsy decisions. We estimated the
      number of prostate cancers diagnosed and prostate biopsies performed if S3M
      replaced CPT in Stockholm, Sweden, by comparing biopsy results in 56 282 men who
      underwent PSA testing according to CPT in Stockholm in 2011 with the 47 688 men
      enrolled in the STHLM3 validation cohort 2012-2015. With the same sensitivity as
      CPT to diagnose Gleason score >=7 prostate cancer, S3M was estimated to reduce
      the number of men biopsied by 53% (95% confidence interval [CI]: 41-65%), avoid
      76% (95% CI: 67-81%) of negative biopsies, and reduce Gleason score 6 cancers by
      23% (95% CI: 6-40%). S3M has the potential to improve prostate cancer diagnostics
      by better selecting men with high risk of GS >=7 prostate cancer. PATIENT
      SUMMARY: We modeled the effect the Stockholm-3 model would have on prostate
      cancer diagnostics if it replaced current clinical practice. We found that
      Stockholm-3 model may substantially reduce the number of biopsies, while
      maintaining the same sensitivity to diagnose clinically significant prostate
      cancer.

PMID- 28753804
TI  - Variability in Outcomes for Patients with Intermediate-risk Prostate Cancer
      (Gleason Score 7, International Society of Urological Pathology Gleason Group 2
      3) and Implications for Risk Stratification: A Systematic Review.
AB  - CONTEXT: Optimal management for patients with intermediate-risk (IR) prostate
      cancer (PCa) remains controversial. Clinical metrics provide guidance on
      appropriate management options. OBJECTIVE: To report estimates for clinically
      relevant outcomes in men with IR PCa based on clinical and pathological features.
      EVIDENCE ACQUISITION: PubMed and programs from key 2015 uro-oncology congresses
      were searched using the terms "intermediate", "Gleason 3 + 4", "Gleason 4 + 3",
      "active surveillance", "treatment", "adverse pathology", AND "prostate cancer."
      Articles meeting prespecified criteria were retrieved. Bibliographies were
      scanned for additional relevant references. EVIDENCE SYNTHESIS: Men with IR PCa
      have a wide range of predicted clinically relevant outcomes. Within the IR
      category, estimate ranges for adverse surgical pathology and 5-yr disease
      progression are 15-64% and 21-91%, respectively. Clinical parameters and
      predictive nomograms refine these estimates, but do not uniformly differentiate
      favorable and unfavorable IR PCa. Variations in study design and data quality in
      source manuscripts mandate caution in interpreting results. CONCLUSIONS: Outcomes
      in IR PCa are heterogeneous. Refinements in personalized risk assessment are
      needed to better select IR PCa patients for surveillance. PATIENT SUMMARY:
      Current and future risk stratification tools may provide additional information
      to identify men with intermediate-risk prostate cancer who may consider active
      surveillance.

PMID- 28753805
TI  - The Urinary Tract Microbiome in Health and Disease.
AB  - CONTEXT: The urinary tract, previously considered a sterile body niche, has
      emerged as the host of an array of bacteria in healthy individuals,
      revolutionizing the urology research field. OBJECTIVE: To review the literature
      on microbiome implications in the urinary tract and the usefulness of
      probiotics/prebiotics and diet as treatment for urologic disorders. EVIDENCE
      ACQUISITION: A systematic review was conducted using PubMed and Medline from
      inception until July 2016. The initial search identified 1419 studies and 89 were
      included in this systematic review. EVIDENCE SYNTHESIS: Specific bacterial
      communities have been found in the healthy urinary tract. Changes in this
      microbiome have been observed in certain urologic disorders such as urinary
      incontinence, urologic cancers, interstitial cystitis, neurogenic bladder
      dysfunction, sexually transmitted infections, and chronic prostatitis/chronic
      pelvic pain syndrome. The role of probiotics, prebiotics, and diet as treatment
      or preventive agents for urologic disorders requires further investigation.
      CONCLUSIONS: There is a microbiome associated with the healthy urinary tract that
      can change in urologic disorders. This represents a propitious context to
      identify new diagnostic, prognostic, and predictive microbiome-based biomarkers
      that could be used in clinical urology practice. In addition, probiotics,
      prebiotics, and diet modifications appear to represent an opportunity to regulate
      the urinary microbiome. PATIENT SUMMARY: We review the urinary microbiome of
      healthy individuals and its changes in relation to urinary disorders. The
      question to resolve is how we can modulate the microbiome to improve urinary
      tract health.

PMID- 28753806
TI  - 68Ga-Labeled Prostate-specific Membrane Antigen Ligand Positron Emission
      Tomography/Computed Tomography for Prostate Cancer: A Systematic Review and Meta
      analysis.
AB  - CONTEXT: 68Gallium prostate-specific membrane antigen (PSMA) ligand 68Ga-HBED-CC
      PSMA (68Ga-PSMA) is a promising radiotracer for positron emission tomography
      (PET)/computed tomography (CT) of prostate cancer. OBJECTIVE: To conduct a meta
      analysis to evaluate detection rate, diagnostic test accuracy, and adverse
      effects of 68Ga-PSMA PET/CT or PET/magnetic resonance imaging (MRI) for staging
      of prostate cancer and for restaging of rising prostate-specific antigen (PSA)
      after initial treatment. EVIDENCE ACQUISITION: Following the Preferred Reporting
      Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, our
      systematic review searched for articles in PubMed and EMBASE databases from 2012
      to July 2016. The reference standard was pathology after biopsy or surgery. The
      analyses used a random effect model and a hierarchical summary receiver operating
      characteristic model. EVIDENCE SYNTHESIS: Fifteen 68Ga-PSMA PET/CT studies with
      1256 patients met the inclusion criteria. Seven studies of staging PET/CT or
      PET/MRI detected a regional site of cancer for 203 of 273 patients (74%). Nine
      studies of restaging PET/CT detected sites of recurrence in 799 of 983 patients
      (81%) with a 50% detection rate (74 of 147 patients) for restaging PSA of 0.2
      0.49 ng/ml and a 53% detection rate (56 of 195 patients) for restaging PSA of
      0.50-0.99 ng/ml. Staging 68Ga-PSMA PET/CT in the studies had higher detection
      rates of sites in the prostate bed than restaging 68Ga-PSMA PET/CT (mean 57% vs
      14%, p=0.031, t test). Both staging and restaging 68Ga-PSMA PET/CT found that a
      subgroup of the patients had metastatic sites in pelvic lymph nodes or distant
      organs. Eight studies of staging PET/CT undertook histologic correlations. We
      performed prostate-segment-based analysis specifically regarding the primary
      cancer lesion for four of these studies, and patient-based analysis specifically
      regarding pelvic lymph node metastases for four other studies. The pooled
      sensitivities for staging in the two groups of studies were 70% and 61%, and the
      pooled specificities were 84% and 97%. None of the studies reported complications
      from the PET/CT imaging. CONCLUSIONS: 68Ga-PSMA PET/CT has clinical relevance to
      detect sites of recurrence for patients with PSA recurrence after radical
      prostatectomy (RP) with PSA levels less than 1.0 ng/ml. PATIENT SUMMARY: Choline
      positron emission tomography (PET)/computed tomography (CT) can detect sites of
      recurrent prostate cancer in an earlier phase of prostate-specific antigen (PSA)
      recurrence than bone scans and CT scans, but choline PET/CT is rarely positive
      for patients with restaging PSA levels under 1 ng/ml. A new radiotracer called
      68Ga-PSMA for PET/CT was able to detect sites of recurring cancer in up to 50% of
      patients who had an early rise in PSA exceeding 0.5 ng/ml after initial radical
      prostatectomy. The published studies did not report adverse effects of 68Ga-PSMA
      PET/CT imaging.

PMID- 28753807
TI  - Diagnostic Needle Biopsies in Renal Masses: Patient and Physician Perspectives.
AB  - BACKGROUND: The utility of renal mass biopsies (RMB) in the diagnosis of kidney
      tumors remains debatable. OBJECTIVE: To assess patient and urologist preferences
      regarding the utilization of RMB. DESIGN, SETTING, AND PARTICIPANTS: Seventy
      three patients diagnosed with renal tumors and 59 board-certified urologists were
      asked to participate in an interview-based study. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Using the standard gamble method we determined the minimal
      accepted accuracy at which RMB would be favored as part of the diagnostic
      process. Clinical and demographic data with potential to affect participants'
      preferences were analyzed. RESULTS AND LIMITATIONS: At the time of the study
      interview, 56 patients (77%) were referred for kidney surgery and 17 (23%) opted
      for surveillance. Overall, 59% of the patients accepted some level of inaccuracy
      (1-20%), whereas 27% refuted a biopsy. Anxiety associated with the possibility of
      missing cancer was the primary determinant (82%) for declining RMB among patients
      referred for surgery, while fear of complications was the primary reason (58%)
      among those undergoing surveillance. Having an academic degree was associated
      with a lower accuracy threshold (p=0.03). Of the 59 participating urologists, 39%
      were reluctant to recommend RMB, primarily because of its inexorable
      nondiagnostic rate. CONCLUSIONS: Most patients and urologists would favor RMB to
      facilitate their definitive treatment decision. Diagnostic accuracy of 95% was
      acceptable by the majority of study participants. The utility of RMB as part of
      the diagnostic algorithm for renal tumors should be discussed with patients,
      emphasizing its potential benefits and limitations. PATIENT SUMMARY: Although
      needle biopsy seems to be an effective tool to differentiate benign from
      malignant kidney lesions, it is not commonly used. Our study shows that most
      patients would opt for a biopsy before definitive treatment decision despite its
      imperfect accuracy. Hence, the option of undergoing renal biopsy should be
      discussed with all patients diagnosed with small renal tumors.

PMID- 28753808
TI  - Undescended testes: Diagnostic Algorithm and Treatment.
AB  - Undescended testis persistently present at the 6th month of life in a term born
      boy should be treated, with the aim of bringing them to a scrotal position until
      the 12th month of life. Acquired undescended testes has to be looked for actively
      and treated at the earliest possible after diagnosis, that might be deferred due
      to a lack of attention and less access to a regular physical exam in older boys
      as opposed to infants.

PMID- 28753809
TI  - Significance of Serum N-glycan Profiling as a Diagnostic Biomarker in Urothelial
      Carcinoma.
AB  - BACKGROUND: The clinical diagnosis of urothelial carcinoma (UC) relies on
      invasive methods in patients with hematuria. Although more sensitive and
      noninvasive screening methods are required, a specific serum biomarker for UC is
      lacking. OBJECTIVE: To examine whether serum glycan-based biomarkers can be
      applied to UC detection. DESIGN, SETTING, AND PARTICIPANTS: Between April 1994
      and June 2016, serum N-glycan concentrations were retrospectively measured in 212
      patients with UC before treatment (UC group) and 212 pair-matched controls using
      glycoblotting and mass spectrometry. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: N-glycan levels were compared between the groups using receiver
      operating characteristic curves to select candidate N-glycans. We created an N
      glycan score based on the combination of candidate N-glycans. The specificity and
      sensitivity of the candidate N-glycan score were evaluated using receiver
      operating characteristic curves. RESULTS AND LIMITATIONS: The N-glycan score was
      calculated using six N-glycans (m/z 1566, m/z 1687, m/z 1769, m/z 1871, m/z 2011,
      and m/z 2337) that were significantly associated with UC. The median N-glycan
      score was significantly higher in the UC group than in the pair-matched control
      group (5.0 vs 1.0, p<0.001). The N-glycan score correctly classified UC patients
      with a sensitivity, specificity, and area under the curve of 93%, 81%, and 0.95,
      respectively. The limitations of our study included its retrospective nature and
      nonclinical setting. CONCLUSIONS: Serum N-glycan content has the potential to be
      a specific and sensitive novel serum biomarker that may improve the accuracy of
      the detection for UC and reduce unnecessary invasive screening. Validation of
      this test in a large-scale prospective study is needed. PATIENT SUMMARY:
      Combination of serum N-glycan (N-glycan score) is a novel serum marker for
      urothelial carcinoma that is expressed by 93% of patients and thus is far more
      sensitive than classic urine cytology. Validation in a large patient cohort is
      needed.

PMID- 28753810
TI  - Validation of Cyclic Adenosine Monophosphate Phosphodiesterase-4D7 for its
      Independent Contribution to Risk Stratification in a Prostate Cancer Patient
      Cohort with Longitudinal Biological Outcomes.
AB  - BACKGROUND: The clinical metrics used to date to assess the progression risk of
      newly diagnosed prostate cancer patients only partly represent the true
      biological aggressiveness of the underlying disease. OBJECTIVE: Validation of the
      prognostic biomarker phosphodiesterase-4D7 (PDE4D7) in predicting longitudinal
      biological outcomes in a historical surgery cohort to improve postsurgical risk
      stratification. DESIGN, PATIENTS, AND METHODS: RNA was extracted from biopsy
      punches of resected tumors from 550 patients. PDE4D7 was quantified using one
      step quantitative reverse transcription-polymerase chain reaction. PDE4D7 scores
      were calculated by normalization of PDE4D7 to reference genes. Multivariate
      analyses were adjusted for clinical prognostic variables. Outcomes tested were:
      prostate-specific antigen relapse, start of salvage treatment, progression to
      metastases, overall mortality, and prostate cancer-specific mortality. The PDE4D7
      score was combined with the clinical risk model Cancer of the Prostate Risk
      Assessment Postsurgical Score (CAPRA-S) using multivariate regression modeling;
      the combined score was tested in post-treatment progression free survival
      prediction. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Correlations with
      outcomes were analyzed using multivariate Cox regression and logistic regression
      statistics. RESULTS AND LIMITATIONS: The PDE4D7 score was significantly
      associated with time-to-prostate specific antigen failure after prostatectomy
      (hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.41-0.67 for each unit
      increase, p<0.0001). After adjustment for postsurgical prognostic variables the
      HR was 0.56 (95% CI: 0.43-0.73, p<0.0001). The PDE4D7 score remained significant
      after adjusting the multi-variate analysis for the CAPRA-S model categories
      (HR=0.54, 95% CI=0.42-0.69, p<0.0001). Combination of the PDE4D7 score with the
      CAPRA-S demonstrated a significant incremental value of 4-6% in 2-yr (p=0.004) or
      5-yr (p=0.003) prediction of progression free survival after surgery. The
      combined model of PDE4D7 and CAPRA-S improves patient selection with very high
      risk of fast disease relapse after primary intervention. CONCLUSIONS: The PDE4D7
      score has the potential to provide independent risk information and to restratify
      patients with clinical intermediate- to high-risk characteristics to a very low
      risk profile. PATIENT SUMMARY: In this report, we studied the potential of a
      novel biomarker to predict outcomes of a cohort of prostate cancer patients who
      underwent surgery more than 10 yr ago. We found that a gene called
      phosphodiesterase-4D7 added extra information to the available clinical data. We
      conclude that the measurement of this gene in tumor tissue may contribute to more
      effective treatment decisions.

PMID- 28753811
TI  - Risk of Upgrading and Upstaging Among 10 000 Patients with Gleason 3+4 Favorable
      Intermediate-risk Prostate Cancer.
AB  - BACKGROUND: It is unknown whether active surveillance can be safely offered to
      patients with Gleason 3+4 favorable intermediate-risk (FIR) prostate cancer.
      OBJECTIVE: To examine the incidence and predictors of upgrading and upstaging
      among patients with Gleason 3+4 FIR disease. DESIGN, SETTING, AND PARTICIPANTS:
      The study involved 10 089 patients in the National Cancer Database diagnosed from
      2010 to 2012 with Gleason 3+4 disease, prostate-specific antigen (PSA) <10ng/ml,
      and cT1c-2a prostate cancer with <50% positive biopsy cores (PBCs) who underwent
      radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic
      regression was used to examine predictors of upgrading (pathologic Gleason >=4+3
      or tertiary Gleason 5 in a Gleason 7 tumor) or upstaging (pT3-4/N1). RESULTS AND
      LIMITATIONS: Some 30.3% of Gleason 3+4 FIR patients were upgraded or upstaged. On
      multivariable analysis, predictors included higher PSA, percentage PBC, age, and
      cT2a versus cT1c (all p<0.001), but not black race (p=0.895). When stratified
      into ordinal variables, PSA 8.1-9.9 versus <=4.0ng/ml (adjusted odds ratio [AOR]
      1.93, 38.3% vs 24.4%), PBC 37.5-49.9% versus <12.5% (AOR 1.79, 37.8% vs 25.1%);
      highest age quartile (>=67 yr) versus lowest (<=55 yr; AOR 1.46, 35.7% vs 24.7%);
      and cT2a versus cT1c (AOR 1.33, 34.3% vs 29.8%) were associated with a higher
      risk of upgrading or upstaging (all p<0.001). Men with PBC <12.5% and PSA
      <=4.0ng/ml had a 21.7% risk of more advanced disease. This increased to 44.3% for
      PBC 37.5-49.9% and PSA 8.1-9.9ng/ml. A limitation of the study is its
      retrospective nature. CONCLUSIONS: Approximately one in three patients with
      Gleason 3+4 FIR harbored disease of higher grade or stage. Younger patients with
      low percentage PBC and PSA and cT1c disease have a lower risk and may be
      candidates for active surveillance. However, widely available clinical
      information is insufficient for predicting the risk of more advanced disease, and
      the development and incorporation of additional tools, including magnetic
      resonance imaging and genomic tests, are necessary. PATIENT SUMMARY: Nearly one
      third of patients with Gleason 3+4 favorable intermediate-risk prostate cancer
      harbor disease of higher grade or higher stage than their biopsy and clinical
      examination suggest. These patients would therefore be poor candidates for active
      surveillance.

PMID- 28753812
TI  - PD-L1 Expression and CD8+ T-cell Infiltrate are Associated with Clinical
      Progression in Patients with Node-positive Prostate Cancer.
AB  - : Prostate cancer (PCa) patients with lymph node invasion at radical
      prostatectomy are at higher risk of tumor recurrence and receive immediate
      androgen deprivation therapy (ADT). While approximately 30% of these patients do
      not experience recurrence, others experience disease recurrence despite ADT, and
      currently no biomarkers can accurately identify them. We analyzed tumors from 51
      patients with node-positive prostate cancer using immunohistochemistry to
      investigate whether expression of the immune checkpoint ligand PD-L1 by tumor
      cells or the density of CD8+ or CD20+ cells are associated with clinical
      progression. Patients with at least 1% PD-L1+ tumor cells had shorter metastasis
      free survival than those with PD-L1- tumors (p=0.008, log-rank test). Univariate
      Cox regression showed that patients with PD-L1+ tumors had almost four times the
      risk of experiencing distant metastases than those with PD-L1- tumors (hazard
      ratio 3.90). In addition, we found that PD-L1 expression was significantly
      associated with CD8+ T-cell density, but not with CD20+ B-cell density. While
      these results need to be confirmed in larger studies, they show that PD-L1 and
      CD8 may be used as biomarkers for node-positive patients at high risk of
      progression. The study also provides a rationale for selecting patients with node
      positive PCa who might benefit the most from adjuvant immunotherapies. PATIENT
      SUMMARY: None of the available biomarkers can identify node-positive prostate
      cancer that will recur after surgery. We found that expression of PD-L1 by tumor
      cells and a high density of CD8+ T cells in tumor are associated with a higher
      risk of clinical progression in men with node-positive prostate cancer.

PMID- 28753813
TI  - Hospital Readmissions After Urological Surgical Procedures in France: A
      Nationwide Cohort Study over 3 Years.
AB  - BACKGROUND: Identifying the predictive factors for hospital readmission is
      required to target preventive measures. OBJECTIVE: To assess the rate of surgical
      readmissions after a urological procedure and the risk factors associated with
      readmission. DESIGN, SETTING, AND PARTICIPANTS: Data from all hospitalizations
      between January 2010 and November 2012 in France, regarding planned urological
      surgeries, were retrieved from the national medical database. To limit
      interactions between recent hospitalizations and surgical interventions, we
      selected only patients who were not hospitalized during the 12 mo preceding the
      urological procedure. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary
      outcome was the rate of readmissions within 30 d after urological surgery. The
      following risk factors for readmission were assessed: sex, age, diagnosis-related
      group, length of stay of initial hospitalization, type of hospitalization
      (conventional or day surgery), hospital volume activity, hospital volume for day
      surgery, and hospital status. Logistic regression multivariate analysis was used
      to assess risk factors. RESULTS AND LIMITATIONS: Overall, 419 787 patients were
      included among whom 77 241 patients (18.40%) were readmitted within the following
      30 d. After multivariate analyses, male sex (odds ratio [OR]=1.84, confidence
      interval [CI] 95%: 1.81-1.88), high level of comorbidity (diagnosis-related group
      3-4 vs 1-2: OR=2.14, CI 95%: 2.10-2.21), and initial management in a private
      hospital (private vs university hospital: OR=1.13, CI 95%: 1.11-1.16; private vs
      public general hospital: OR=1.21, CI 95%: 1.18-1.23) were associated with a
      higher risk of readmission within 30 d. CONCLUSIONS: Reported readmission rate
      within 30 d after a planned a urological procedure was nearly 20%. PATIENT
      SUMMARY: In this French national study, we investigated the readmission rate
      within 30 d after a planned urological procedure in a large French population and
      discovered it was nearly 20%.

PMID- 28753814
TI  - Functional Comparison of Renal Tumor Enucleation Versus Standard Partial
      Nephrectomy.
AB  - BACKGROUND: Tumor enucleation (TE) optimizes parenchymal preservation and could
      yield better function than standard partial nephrectomy (SPN), although data on
      this are conflicting. OBJECTIVE: To compare functional outcomes for TE and SPN
      strategies. DESIGN, SETTING, AND PARTICIPANTS: Patients managed with partial
      nephrectomy (PN) with necessary data for analysis of preservation of ipsilateral
      parenchymal mass (IPM) and global glomerular filtration rate (GFR) from two
      centers were included. All studies were required <2 mo before and 3-12 mo after
      surgery. Patients with a solitary kidney or multifocal tumors were excluded.
      INTERVENTION: Partial nephrectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Vascularized IPM was estimated from contrast-enhanced CT scans preoperatively and
      postoperatively. Serum creatinine-based estimates of global GFR were also
      obtained in the same timeframes. Univariable and multivariable linear regression
      evaluated factors associated with new-baseline global GFR. RESULTS/LIMITATIONS:
      Analysis included 71 TE and 373 SPN cases. The median preoperative global GFR was
      comparable for TE and SPN (75 vs 78ml/min/1.73m2; p=0.6). The median tumor size
      was 3.0cm for TE and 3.3cm for SPN (p=0.03). The median RENAL score was 7 in both
      cohorts. For TE, warm ischemia and zero ischemia were used in 51% and 49% of
      cases, respectively. For SPN, warm ischemia and cold ischemia were used in 72%
      and 28% of patients, respectively. Capsular closure was performed in 46% of TE
      and 100% of SPN cases (p<0.001). Positive margins were found in 8.5% of TE and
      4.8% of SPN patients (p=0.2). The median vascularized IPM preserved was 95%
      (interquartile range [IQR] 91-100%) for TE and 84% (IQR 76-92%) for SPN
      (p<0.001). The median global GFR preserved was 101%(IQR 93-111%) and 89% (IQR 81
      96%) for TE and SPN, respectively (p<0.001). On multivariable analysis, resection
      strategy, preoperative GFR, and vascularized IPM preserved were all significantly
      associated (p<0.001) with new-baseline global GFR. Limitations include the
      retrospective design and the lack of resection outcome data. CONCLUSIONS: Our
      analysis suggests that TE has potential for maximum IPM preservation compared to
      SPN and may provide optimized functional recovery. Further investigation will be
      required to evaluate the clinical significance of these findings. PATIENT
      SUMMARY: Tumor enucleation for kidney cancer involves dissection along the tumor
      capsule and optimally preserves normal kidney tissue, which may lead to better
      functional recovery. The importance of this approach in various clinical settings
      will require further investigation.

PMID- 28753815
TI  - Phimosis in a 10-yr-old Boy Without Urinary Infection-How to Inform Parents: For
      Circumcision.
AB  - Circumcision can be a viable option for phimosis in a 10-yr-old boy, also if
      asymptomatic, in the presence of skin alterations or if the parents prefer avoid
      observation. Morbidity is minimal if the procedure is performed in a hospital
      setting.

PMID- 28753816
TI  - Impact of High-risk Features and Effect of Neoadjuvant Chemotherapy in Urothelial
      Cancer Patients with Invasion into the Lamina Propria on Transurethral Resection
      in the Absence of Deep Muscle Invasion.
AB  - BACKGROUND: High-risk non-muscle-invasive bladder cancer (NMIBC) that invades
      into the lamina propria is frequently understaged and is associated with a risk
      of lymph node metastasis and death. OBJECTIVE: To identify high-risk features
      (HRFs) for NMIBC that may identify patients with poorer prognosis who may benefit
      from neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). DESIGN,
      SETTING, AND PARTICIPANTS: We performed a single-center retrospective review of
      patients who underwent RC for NMIBC with invasion into the lamina propria between
      1995 and 2013. HRFs included hydronephrosis, abnormal examination under
      anesthesia, lymphovascular invasion, or variant histology. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: Pathology at RC, and overall (OS) and disease-specific
      (DSS) survival were evaluated and analyzed by Fisher's exact test, Student t
      test, Cox proportional hazards regression analysis, and the Kaplan-Meier method.
      RESULTS AND LIMITATIONS: We identified 336 patients with a median follow-up of
      130 mo. Of these, 159 (47%) had no HRF, 140 (41.5%) had one HRF, and 37 (11%) had
      >=2 HRFs. At RC, patients with >=2 HRFs had a significantly higher rate of
      pathologic T stage upstaging and lymph node metastasis (p<0.05). Median OS was
      139 mo for those with no HRF, 127 mo for those with one HRF, and 56 mo for those
      with >=2 HRF (p=0.0057). HRFs are also associated with a decreased DSS
      (p=0.0009). Patients with >=2 HRFs (11/37) who received NAC showed improved OS
      (21% vs 55% 5-yr OS, p=0.0353) and trended toward an improvement in DSS (25% vs
      56% 5-yr OS, p=0.0716) compared with RC alone. CONCLUSIONS: The presence of >=2
      HRFs in NMIBC invading the lamina propria is associated with worse pathology at
      RC and a significant decrease in OS and DSS. NAC appears to provide benefit for
      these patients. Limitations include retrospective design and limited sample size.
      PATIENT SUMMARY: The presence of high-risk features in urothelial cancer with
      invasion into the lamina propria has a worse prognosis that may be mitigated by
      neoadjuvant chemotherapy.

PMID- 28753817
TI  - Detection of Lymph Node Metastasis in Patients with Bladder Cancer using Maximum
      Standardised Uptake Value and 18F-fluorodeoxyglucose Positron Emission
      Tomography/Computed Tomography: Results from a High-volume Centre Including Long
      term Follow-up.
AB  - BACKGROUND: Preoperative staging with 18F-fluorodeoxyglucose (18F-FDG) positron
      emission tomography (PET) combined with computed tomography (CT) is used for the
      evaluation of metastatic disease in patients with invasive bladder cancer. The
      use of quantification with maximum standardized uptake value (SUVmax) of regional
      lymph nodes (LNs) has been suggested to increase the diagnostic ability for
      detection of malignancy. OBJECTIVE: Assessment of the utility and clinical
      relevance of SUVmax in 18F-FDG PET in detecting regional nodal metastases in
      patients considered for radical cystectomy. DESIGN, SETTING, AND PARTICIPANTS:
      From 2011 to 2014, we identified a total of 119 patients with urothelial
      carcinoma who underwent radical cystectomy with extended LN dissection;
      additionally, 12 patients were identified by preoperative biopsy. All patients
      underwent 18F-FDG PET/CT before treatment recommendation. Pathological findings
      were compared with preoperative PET/CT staging and analysed in a regional- or
      patient-based model according to SUVmax values. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: In total, 2291 LNs were identified in 131 patients;
      locoregional involvement of 85 LNs were confirmed in 34 patients. RESULTS AND
      LIMITATIONS: SUVmax >2 analysis: sensitivity+/-95% confidence interval of 79.4%
      (62.1-91.3) and specificity 66.5% (55.7-75.3). SUVmax >4 based analysis:
      sensitivity was 61.8% (43.6-77.8) and specificity was 84.5% (75.8-91.1). Two
      years of follow-up implied that higher SUVmax is correlated with higher
      recurrence risk, independent of conventional pathological findings. CONCLUSIONS:
      18F-FDG PET/CT using SUVmax of LNs is a useful tool for preoperative evaluation
      of pelvic LN metastases from invasive bladder cancer and contributes to the
      selection of patients for personalized treatment. PATIENT SUMMARY: In this
      report, we establish that it is possible to identify disease from bladder cancer
      in the lymphatic tissue surrounding the bladder using a scan analysis. This
      assists in the selection of treatment for patients with bladder cancer and may
      spare patients from unnecessary procedures.

PMID- 28753818
TI  - Phimosis in a 10-yr-old Boy Without Urinary Infection-How to Inform Parents:
      Against Circumcision.
AB  - In a 10-yr-old boy with no abnormalities or symptoms other than nonretractability
      of the foreskin, the foreskin should be preserved. If treatment is needed, local
      corticoid application should be used as first-line therapy, as it gives excellent
      results in up to 90% of cases, before removing this sensitive part of the body.

PMID- 28753819
TI  - Enhanced Recovery After Surgery Protocols to Reduce Morbidity in the Aging
      Patient.
AB  - Enhanced recovery after surgery protocols have the potential to reduce
      postoperative morbidity after major urologic surgery for the aging patient.

PMID- 28753820
TI  - Clinical Lymphadenopathy in Urothelial Cancer: A Transatlantic Collaboration on
      Performance of Cross-sectional Imaging and Oncologic Outcomes in Patients Treated
      with Radical Cystectomy Without Neoadjuvant Chemotherapy.
AB  - BACKGROUND: Data regarding clinical node metastases (cN+) in patients undergoing
      radical cystectomy (RC) are scarce. OBJECTIVE: To evaluate the performance of
      conventional imaging in detecting cN+ and analyze the impact of cN+ on survival
      among patients treated with RC without neoadjuvant chemotherapy (NAC). DESIGN,
      SETTING, AND PARTICIPANTS: Data from three independent centers of consecutive
      patients with bladder cancer treated with RC without NAC were analyzed. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: cN+ was defined as pelvic nodes >8mm or
      abdominal nodes >10mm in maximum short-axis diameter as detected via preoperative
      computed tomography or magnetic resonance imaging. Performance characteristics
      were evaluated considering pN+ disease as the reference standard. Multivariable
      Cox regression analyses were performed for prediction of survival. RESULTS AND
      LIMITATIONS: Overall, 196 patients (7.1%) had cN+ disease before RC and pN+
      status was confirmed for 122 of them (62.2%). cN+ status in the overall
      population had sensitivity of 18% and specificity of 96% with a calculated area
      under the curve of 57%. The median follow-up was 108 mo. On multivariable
      analyses, cN+pN+ (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.26-2.68)
      and cN-pN+ (HR 2.36, 95% CI 1.90-2.92) were predictors of CSM (both p<0.001).
      Conversely, cN+pN- status was not associated with worse survival outcomes (p >
      0.2). CONCLUSIONS: Our study confirms the poor accuracy of conventional
      preoperative imaging in assessing nodal disease status. cN status had no
      independent impact on survival when all confounders were evaluated, and
      potentially curative treatments should not be withheld on the basis of clinical
      nodal status alone. PATIENT SUMMARY: The accuracy of conventional imaging
      techniques for detection of pathologic lymph node-positive disease before radical
      cystectomy for bladder cancer is suboptimal. The presence of clinical lymph node
      positivity on preoperative imaging is not an independent predictor of oncologic
      outcomes, and if the node invasion is not confirmed at radical cystectomy, these
      patients may have good long-term outcomes.

PMID- 28753821
TI  - Combining of ETHOS Operating Ergonomic Platform, Three-dimensional Laparoscopic
      Camera, and Radius Surgical System Manipulators Improves Ergonomy in Urologic
      Laparoscopy: Comparison with Conventional Laparoscopy and da Vinci in a Pelvi
      Trainer.
AB  - BACKGROUND: Posture, vision, and instrumentation limitations are the main
      predicaments of conventional laparoscopy. OBJECTIVE: To combine the ETHOS
      surgical chair, the three-dimensional laparoscope, and the Radius Surgical System
      manipulators, and compare the system with conventional laparoscopy and da Vinci
      in terms of task completion times and discomfort. DESIGN, SETTING, AND
      PARTICIPANTS: Fifteen trainees performed the three main laparoscopic suturing
      tasks of the Heilbronn training program (IV: simulation of dorsal venous complex
      suturing; V: circular suturing of tubular structure; and VI: urethrovesical
      anastomosis) in a pelvi trainer. The tasks were performed conventionally,
      utilizing the three devices, and robotically. Task completion times were recorded
      and the surgeon discomfort was evaluated using questionnaires. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Task completion times were compared using
      nonparametric Wilcoxon signed rank test and ergonomic scores were compared using
      Pearson chi-square test. RESULTS AND LIMITATIONS: The use of the full
      laparoscopic set (ETHOS chair, three-dimensional laparoscopic camera, Radius
      Surgical System needle holders), resulted in a significant improvement of the
      completion time of the three tested tasks compared with conventional laparoscopy
      (p<0.001) and similar to da Vinci surgery. After completing Tasks IV, V, and VI
      conventionally, 12 (80%), 13 (86.7%), and 13 (86.7%) of the 15 trainees,
      respectively, reported heavy total discomfort. The full laparoscopic system
      nullified heavy discomfort for Tasks IV and V and minimized it (6.7%) for the
      most demanding Task VI. Especially for Task VI, all trainees gained benefit, by
      using the system, in terms of task completion times and discomfort. The limited
      trainee robotic experience and the questionnaire subjectivity could be a
      potential limitation. CONCLUSIONS: The ergonomic laparoscopic system offers
      significantly improved task completion times and ergonomy than conventional
      laparoscopy. Furthermore, it demonstrates comparable results to robotic surgery.
      PATIENT SUMMARY: The study was conducted in a pelvi trainer and no patients were
      recruited.

PMID- 28753822
TI  - Five-year Outcomes for a Prospective Randomised Controlled Trial Comparing
      Laparoscopic and Robot-assisted Radical Prostatectomy.
AB  - BACKGROUND: The literature is lacking randomised controlled trials comparing
      robot-assisted (RARP) and laparoscopic (LRP) radical prostatectomy, especially
      for follow-up >1 yr. OBJECTIVE: To report 5-yr outcomes for our previously
      published prospective randomised study comparing RARP and LRP. DESIGN, SETTING,
      AND PARTICIPANTS: From January 2010 to January 2011, 120 patients with organ
      confined prostate cancer were enrolled and randomly assigned to RARP or LRP.
      INTERVENTION: A single surgeon performed all interventions using the same
      transperitoneal anterograde technique. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Continence, potency, and serum prostate-specific antigen were assessed
      postoperatively at 1, 3, 6, and 12 mo, and then every 6 mo until 60 mo. At the
      end of the follow-up period, patients were administered questions 1 and 46 of the
      Expanded Prostate Cancer Index Composite questionnaire to assess their
      satisfaction with the intervention and general health status. A generalised
      estimating equations model was used to compare time series data for functional
      results, and Kaplan-Meier and Cox models were used to analyse oncologic outcomes.
      RESULTS AND LIMITATIONS: The probability of achieving continence (odds ratio [OR]
      2.47, p<0.021) and potency (OR 2.35, p<0.028) over time was more than doubled for
      the RARP compared to the LRP group. There was no difference between the two
      approaches in terms of patient survival. Pathologic Gleason score, positive
      surgical margins, and pT stage were associated with significantly higher
      biochemical recurrence in Cox multivariate models. Patient satisfaction with the
      intervention and their general health status was significantly higher in the RARP
      group. CONCLUSIONS: Throughout the 5-yr follow-up, RARP yielded better functional
      results compared to LRP, without compromising oncologic outcomes. PATIENT
      SUMMARY: In this report we looked at 5-yr outcomes for a study comparing robot
      assisted radical prostatectomy (RARP) and laparascopic radical prostatectomy for
      the treatment of prostate cancer. We found that continence and potency are better
      among patients treated with RARP, while oncologic results are comparable.

PMID- 28753824
TI  - Body Composition in Relation to Clinical Outcomes in Renal Cell Cancer: A
      Systematic Review and Meta-analysis.
AB  - CONTEXT: Several studies suggest that body composition (ie, body proportions of
      muscle and fat defined by computed tomography) is associated with clinical
      outcomes of several cancer types, including renal cell cancer (RCC). OBJECTIVE:
      To conduct a systematic review and meta-analysis of the evidence on body
      composition in relation to clinical outcomes in RCC. EVIDENCE ACQUISITION:
      Literature was reviewed through October 2016 using PubMed and Embase. We included
      studies investigating computed tomography-measured cross-sectional areas of
      visceral adipose tissue (VAT), perinephric fat, subcutaneous adipose tissue
      (SAT), skeletal muscle index (SMI), and skeletal muscle radiodensity (SMD) in
      relation to perioperative outcomes, treatment toxicity, and survival in RCC
      patients. EVIDENCE SYNTHESIS: We included 28 studies with a total of 6608
      patients. Binary classification of body composition was used in most studies. In
      metastatic RCC (mRCC) patients treated with antiangiogenic drugs, dose-limiting
      toxicity was more frequent in patients with low versus high SMI (four studies,
      risk difference = 16%, 95% confidence interval [CI]: 2-31%, p = 0.03, I2 = 26%).
      Low versus high SMI (six studies, hazard ratio = 1.48, 95% CI: 1.08-2.03, p =
      0.02, I2 = 28%) and SMD (four studies, HR = 1.56, 95% CI: 1.20-2.03, p = 0.0008,
      I2 = 0%) were associated with an increased risk of overall mortality in mRCC. Low
      versus high VAT and perinephric fat were not consistently associated with
      perioperative outcomes and survival. No associations for SAT were found.
      CONCLUSIONS: Low SMI is associated with increased dose-limiting toxicity, and low
      SMI and SMD are associated with increased overall mortality in mRCC. The
      association of VAT, perinephric fat, and SAT with clinical outcomes needs further
      investigation, also in localized RCC. PATIENT SUMMARY: We reviewed studies
      assessing the association of body composition with clinical outcomes in renal
      cell cancer. We demonstrated higher risk of dose-limiting toxicity and overall
      mortality for metastatic renal cell cancer patients with low versus high skeletal
      muscle index or skeletal muscle radiodensity, but observed inconsistent
      associations with visceral adipose tissue and perinephric fat.

PMID- 28753823
TI  - Is There an Association Between Ambient Air Pollution and Bladder Cancer
      Incidence? Analysis of 15 European Cohorts.
AB  - BACKGROUND: Ambient air pollution contains low concentrations of carcinogens
      implicated in the etiology of urinary bladder cancer (BC). Little is known about
      whether exposure to air pollution influences BC in the general population.
      OBJECTIVE: To evaluate the association between long-term exposure to ambient air
      pollution and BC incidence. DESIGN, SETTING, AND PARTICIPANTS: We obtained data
      from 15 population-based cohorts enrolled between 1985 and 2005 in eight European
      countries (N=303431; mean follow-up 14.1 yr). We estimated exposure to nitrogen
      oxides (NO2 and NOx), particulate matter (PM) with diameter <10MUm (PM10),
      <2.5MUm (PM2.5), between 2.5 and 10MUm (PM2.5-10), PM2.5absorbance (soot),
      elemental constituents of PM, organic carbon, and traffic density at baseline
      home addresses using standardized land-use regression models from the European
      Study of Cohorts for Air Pollution Effects project. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: We used Cox proportional-hazards models with adjustment for
      potential confounders for cohort-specific analyses and meta-analyses to estimate
      summary hazard ratios (HRs) for BC incidence. RESULTS AND LIMITATIONS: During
      follow-up, 943 incident BC cases were diagnosed. In the meta-analysis, none of
      the exposures were associated with BC risk. The summary HRs associated with a 10
      MUg/m3 increase in NO2 and 5-MUg/m3 increase in PM2.5 were 0.98 (95% confidence
      interval [CI] 0.89-1.08) and 0.86 (95% CI 0.63-1.18), respectively. Limitations
      include the lack of information about lifetime exposure. CONCLUSIONS: There was
      no evidence of an association between exposure to outdoor air pollution levels at
      place of residence and risk of BC. PATIENT SUMMARY: We assessed the link between
      outdoor air pollution at place of residence and bladder cancer using the largest
      study population to date and extensive assessment of exposure and comprehensive
      data on personal risk factors such as smoking. We found no association between
      the levels of outdoor air pollution at place of residence and bladder cancer
      risk.

PMID- 28753825
TI  - Perceived Role of Social Media in Urologic Knowledge Acquisition Among Young
      Urologists: A European Survey.
AB  - BACKGROUND: Social media (SoMe) are increasingly being integrated into personal
      and professional life, with urology being a leading medical specialty in SoMe
      adoption. OBJECTIVE: We aimed to assess the perceived role of SoMe in urologic
      knowledge acquisition among young urologists across Europe. DESIGN, SETTING, AND
      PARTICIPANTS: Members of the European Society of Residents in Urology designed a
      20-item online survey via surveymonkey.com. The survey was designed in accordance
      with Checklist for Reporting Results of Internet E-Surveys (CHERRIES) guidelines
      and was distributed via e-mail and social media in 23 European countries to
      urology residents and young urologists. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Statistical Package for the Social Sciences (SPSS) software was used
      for descriptive statistics and statistical analysis. For comparative analysis the
      Mann-Whitney U test was used. RESULTS AND LIMITATIONS: A total of 316 young
      urologists with a mean age of 31.2+/-3.9 yr responded to the survey. Of the
      respondents, 99% use SoMe in a personal and/or professional way. YouTube and
      LinkedIn are the most frequently used platforms for professional use. SoMe were
      ranked in third place as an information source for urologic news/updates, lying
      behind journals and websites but ahead of congresses and books. Video content
      from YouTube or other sources was ranked as a preferred tool to see/understand
      surgical techniques ahead of websites and reference books. 61% follow urologic
      associations, 47% follow urologic events, 44% follow urologic journals, and 39%
      follow urologic experts on SoMe. The perceived influence of SoMe on urology
      knowledge was rated as moderate to high by 63% and as low to none by 37% of young
      urologists. Of the respondents, 44% apply guidelines on the appropriate use of
      SoMe in urology. CONCLUSIONS: SoMe play a significant role in knowledge
      acquisition by young urologists in Europe. Physicians, organizations, and
      institutions should strive to spread and provide valuable educational content
      through SoMe. PATIENT SUMMARY: Social media can be valuable for education in
      urology because it is useful to keep abreast of new developments in this field of
      medicine.

PMID- 28753826
TI  - Programmed Death-ligand 1 Expression in Upper Tract Urothelial Carcinoma.
AB  - BACKGROUND: Urothelial carcinoma (UC) is the most common malignancy of the
      urinary tract. Upper tract (renal pelvis and ureter) urothelial carcinomas (UTUC)
      account for approximately 5% of UCs but a significant subset are invasive and
      associated with poor clinical outcomes. OBJECTIVE: To evaluate programmed death
      ligand 1 (PD-L1) expression in UTUC. DESIGN, SETTING, AND PARTICIPANTS: UTUC
      cases from 1997-2016 were retrospectively identified from the surgical pathology
      database at a single large academic institution. The cohort included 149 cases:
      27 low-grade and 24 high-grade pathologic T (pT)a, 29 pT1, 23 pT2, 38 pT3, and
      eight pT4. PD-L1 immunohistochemistry (IHC) was performed on representative whole
      tumor sections using anti-PD-L1 primary antibody clone 5H1. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: PD-L1 expression was evaluated using a previously
      established cut-off for positivity (>= 5% membranous staining). Association
      between PD-L1 IHC expression and clinicopathologic parameters was examined with
      Fisher's exact test; the effect of PD-L1 expression on cancer-specific mortality
      was assessed using the Cox proportional hazard model. RESULTS AND LIMITATIONS:
      Approximately one-third (32.7%) of invasive primary UTUC and 23.5% of all primary
      UTUC (invasive and noninvasive tumors) demonstrated positive PD-L1 expression.
      Positive PD-L1 expression was associated with high histologic grade, high
      pathologic stage, and angiolymphatic invasion. Cancer-specific survival was not
      significantly associated with positive PD-L1 expression using a 5% cut-off. Study
      limitations include the retrospective nature and the fact that PD-L1 expression
      by IHC is an imperfect surrogate for response to therapy. CONCLUSIONS: Positive
      PD-L1 expression in approximately one-third of primary invasive UTUC and
      association with high-risk clinicopathologic features provide a rational basis
      for further investigation of PD-L1-based immunotherapeutics in these patients.
      PATIENT SUMMARY: Upper tract urothelial carcinoma is often associated with poor
      clinical outcome. While current treatment options for advanced upper tract
      urothelial carcinoma are limited, programmed death-ligand 1 positivity in
      approximately one-third of invasive tumors provides a rational basis for further
      investigation of programmed death-ligand 1-based immunotherapeutics in these
      patients.

PMID- 28753827
TI  - The CPC Risk Calculator: A New App to Predict Prostate-specific Antigen
      Recurrence During Follow-up After Radical Prostatectomy.
AB  - BACKGROUND: It can be challenging to predict the risk of biochemical recurrence
      (BR) during follow-up after radical prostatectomy (RP) in men who have
      undetectable prostate-specific antigen (PSA), even years after surgery.
      OBJECTIVE: To establish and validate a contemporary nomogram that predicts the
      absolute risk of BR every year after RP in men with undetectable PSA while
      accounting for competing risks of death. DESIGN, SETTING, AND PARTICIPANTS: A
      total of 3746 patients from Rigshospitalet (Copenhagen, Denmark) and Stanford
      Urology (Stanford, CA, USA) who underwent RP between 1995 and 2013 were included.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to BR was defined as the
      first PSA result >=0.2 ng/ml. BR risk was computed using multiple cause-specific
      Cox regression including preoperative PSA, pT category, RP Gleason score (GS),
      and surgical margin (R) status. Death without BR was considered a competing
      event. The nomogram presents the future risk of BR for a man who is alive and
      without BR at the time of follow-up. Validation assessed the discrimination and
      accuracy using time-dependent area under the curve and Brier scores. RESULTS AND
      LIMITATIONS: The nomogram predicts risk of BR up to 12 yr after RP at an
      individual level. As example, the risk of BR for a man with pT3a, R-, GS 3 + 4,
      and preoperative PSA <=10 ng/ml followed for 5 yr with undetectable PSA is 18%
      for the next 5 yr. External validation demonstrated both high accuracy and
      discrimination. The CPC Risk Calculator is available as a free Android and iOS
      App. Declining discrimination and accuracy after 7 yr of follow-up is the main
      limitation. CONCLUSIONS: This nomogram can be used as a tool to inform men with
      undetectable PSA during follow-up after RP about their future risk of BR, and may
      aid in decisions on the necessity for further follow-up. The nomogram is the
      first to be available as a free app. PATIENT SUMMARY: We developed an easily
      interpretable nomogram to evaluate the risk of prostate-specific antigen
      elevation (cancer recurrence) following complete removal of the prostate (radical
      prostatectomy). The tool can aid both physicians and patients in evaluating the
      future risk of cancer recurrence during follow-up after surgery. The model is
      available as a free mobile app that can be downloaded from the App Store.

PMID- 28753828
TI  - Risk of Testosterone Flare in the Era of the Saturation Model: One More
      Historical Myth.
AB  - CONTEXT: When luteinizing hormone-releasing hormone (LHRH) agonists were
      introduced in the 1980s, it was universally believed that the initial transient
      rise in serum testosterone (T), termed T flare, caused rapid prostate cancer
      (PCa) growth and led to disease progression, complications, and death. It became
      routine to offer antiandrogens (AAs) to prevent these risks. However, over the
      last decade, it has become recognized that androgens have a finite ability to
      stimulate PCa growth (the saturation model), providing a theoretical challenge to
      the risks of T flare. OBJECTIVE: To review evidence for the risks associated with
      T flare from a modern perspective, specifically prostate-specific antigen (PSA)
      flare, disease progression, and spinal cord compression. EVIDENCE ACQUISITION: An
      Ovid Medline database search was conducted to identify articles related to
      "testosterone flare", "disease flare", and "PSA flare" associated with LHRH
      agonists. The literature review included papers published from May 1, 1980
      through May 1, 2016. Key search terms included, luteinizing hormone-releasing
      hormone, gonadotropin-releasing hormone, and antiandrogens. EVIDENCE SYNTHESIS:
      Initial administration of LHRH agonists uniformly results in peak increases in
      serum T by 40-100% on days 2-3, returning to baseline by days 7-8, after which T
      declines to castrate levels by approximately 2-3 wk. Of six LHRH agonist studies
      reporting PSA during the period of T flare, five showed no significant rise in
      PSA despite the presence of advanced disease with mean baseline PSA as high as
      >=500ng/ml. Evidence for disease flare was limited to one report of greater bone
      pain with LHRH agonists alone versus LHRH agonists with AAs. Three other RCTs
      reported no disease flare. Rates of spinal cord compression were no greater for
      LHRH agonists alone compared with castration or estrogen treatment. We identified
      no studies of men treated with LHRH agonists versus placebo/no treatment to
      assess the effects of LHRH agonists compared with the natural history of advanced
      PCa. CONCLUSIONS: Although T flare has been considered risky for 30 yr, a modern
      review of the evidence collected primarily in the 1980s and 1990s fails to
      support this view. Specifically, T flare does not appear to be associated with
      significantly increased PSA, disease progression, or adverse events, even in men
      with widely metastatic disease. These results are consistent with the saturation
      model, first introduced in 2006. There seems little value in adding AA to LHRH
      agonists, except possibly for men with extensive vertebral metastases and serum T
      concentrations well below the saturation point of approximately 250ng/dl
      (8.7nmol/l). PATIENT SUMMARY: A review of the literature reveals no evidence for
      increased risks associated with testosterone flare from the initiation of
      luteinizing hormone-releasing hormone (LHRH) agonists. This appears to be an
      unsupported belief from an earlier era when our understanding of testosterone's
      relationship to prostate cancer was less sophisticated. Except in rare instances,
      there appears to be no need to use an androgen blocker when beginning treatment
      with LHRH agonists.

PMID- 28753829
TI  - Erratum to "Trends in Antibiotic Resistance in Urologic Practice" [Eur Urol Focus
      2016;2:363-73].

PMID- 28753830
TI  - Intracavernous Injections of Bone Marrow Mononucleated Cells for Postradical
      Prostatectomy Erectile Dysfunction: Final Results of the INSTIN Clinical Trial.
AB  - : We recently reported stage I of a phase 1/2 clinical trial of cell therapy to
      treat postradical prostatectomy erectile dysfunction (INSTIN, INtra-cavernous
      STem-cell INjection clinical trial, NCT01089387). In this first stage, four doses
      of intracavernous autologous bone marrow mononuclear cells (BM-MNCs) were tested
      in 12 patients. Here, we report the results of stage II, in which six additional
      patients received the optimal dose identified in stage I (109 BM-MNCs), and the
      long-term results in the 12 patients included in stage I. The objectives were to
      assess the safety and efficacy of this new treatment. In stage II, no patients
      had side effects, and the erectile function improvements were similar to those
      seen in stage I: after 6 months, significant improvements versus baseline were
      noted in International Index of Erectile Function-15 intercourse satisfaction
      (7.8+/-3.1 vs 2.2+/-3.4, p=0.033) and erectile function (18+/-8.3 vs 3.7+/-4.1,
      p=0.035) domains. In stage I patients, after a mean follow-up of 62.1+/-11.7 mo,
      there were no prostate cancer recurrences, and erectile function scores were
      somewhat lower compared with the 1-yr time point. These findings suggest that
      intracavernous BM-MNC injections are safe and improve erectile function. The
      decline in erectile function over time suggests a need for assessing repeated
      injections. PATIENT SUMMARY: We report a phase 1/2 pilot clinical trial of cell
      therapy consisting in intracavernous injection of bone marrow mononuclear cells
      to treat postradical prostatectomy erectile dysfunction. Erectile function was
      improved after 6 mo in the patients given 1*109 cells. No serious side effects
      (life threatening or requiring hospitalisation) occurred after a mean follow-up
      of 62.1 mo in the first 12 patients.

PMID- 28753831
TI  - Balancing Overdiagnosis and Early Detection of Prostate Cancer using the
      Stockholm-3 Model.
AB  - The S3M (Stockholm-3 Model) test improves discrimination for high-grade (Gleason
      score >= 7) prostate cancer compared with prostate-specific antigen (PSA)
      testing. Published results from the Stockholm-3 study represent a snapshot of
      possible outcomes for prostate cancer detection using the S3M test. In this brief
      report, we show how the full range of cancer detection rates and percent saved
      biopsies depend on the chosen S3M cut-off for recommending prostate biopsy. Using
      data from the Stockholm-3 validation cohort (n=47 688), we calculated the cancer
      detection rates and percent saved biopsies for various S3M test cut-offs in men
      with PSA >=1ng/ml. Cancer detection rates decline and fewer prostate biopsies
      have to be performed with increasing test cut-offs. Primarily, S3M test values
      between 7% and 14% can be considered for biopsy decision cut-offs (10% risk of
      Gleason score >= 7 corresponds to PSA=3 ng/ml); the exact cutoff can be chosen to
      fit different healthcare systems and, indeed, individual men. PATIENT SUMMARY:
      The Stockholm-3 Model test improves the detection of high-grade prostate cancer
      compared with prostate-specific antigen. In this brief report, we show how the
      cut-off used for recommending prostate biopsies affects the number of detected
      cancers and performed biopsies. The exact cut-off used can be chosen to fit
      different individuals and healthcare systems.

PMID- 28753832
TI  - Longitudinal Changes in Serum Levels of Testosterone and Luteinizing Hormone in
      Testicular Cancer Patients after Orchiectomy Alone or Bleomycin, Etoposide, and
      Cisplatin.
AB  - BACKGROUND: Controversy exists whether Leydig cells recover after testicular
      cancer (TC) treatment or whether premature hormonal aging will occur. OBJECTIVE:
      Evaluate serial changes in total testosterone (TT) and luteinizing hormone (LH)
      in patients treated with orchiectomy alone (Stage I) or combination chemotherapy
      with bleomycin, etoposide, and cisplatin (BEP). DESIGN, SETTINGS, AND
      PARTICIPANTS: Changes in TT and LH were investigated during 5-yr follow-up (Stage
      I: n=75, BEP: n=81). A selected group of TC patients with mild Leydig cell
      dysfunction (LH >= 8 IU/l) were followed for a longer period (Stage I: n=20, BEP:
      n=23). An age-matched control group of 839 healthy men served as controls for TT
      and LH levels. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Changes in age
      adjusted TT and LH were evaluated separately in each treatment group with
      univariate linear regression analysis. The proportion of patients initiating
      testosterone substitution during follow-up was calculated. RESULTS AND
      LIMITATIONS: In the 75 Stage I patients there were no significant changes in LH
      and TT, while in the 81 BEP treated patients there was a significant decline in
      LH during follow-up (-24.2 percentage point/yr, 95% confidence interval: -38.5 to
      -9.9, p=0.001). In total, 11% of Stage I patients and 15% of BEP-treated patients
      initiated testosterone substitution. In the 23 BEP-treated patients with mild
      Leydig cell dysfunction there was a significant decline in age-adjusted TT (-0.9
      percentage point/yr, 95% confidence interval: -1.8 to -0.04, p=0.04), while in
      the 20 Stage I patients there were no significant changes in age-adjusted LH and
      TT. Limitations include the retrospective study design. CONCLUSIONS: TT remained
      stable during 5-yr follow-up in TC patients treated with orchiectomy alone or
      BEP. BEP-treated patients with mild Leydig cell dysfunction during follow-up were
      at risk of long-term testicular failure and evaluation of Leydig cell function
      beyond follow-up should be considered in this group of patients. PATIENT SUMMARY:
      This study shows that the majority of testicular cancer survivors had stable
      testosterone levels after treatment for testicular cancer. However, 11-15% of
      patients needed testosterone substitution after treatment.

PMID- 28753833
TI  - Training, Research, and Working Conditions for Urology Residents in Germany: A
      Contemporary Survey.
AB  - BACKGROUND: Excellent uniform training of urology residents is crucial to secure
      both high-quality patient care and the future of our specialty. Residency
      training has come under scrutiny following the demands of subspecialized care,
      economical aspects, and working hour regulations. OBJECTIVE: To comprehensively
      assess the surgical training, research opportunities, and working conditions
      among urology residents in Germany. DESIGN, SETTING, AND PARTICIPANTS: We sent a
      29-item online survey via email to 721 members of the German Society of Residents
      in Urology. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive analyses
      were conducted to describe the surveys' four domains: (1) baseline
      characteristics, (2) surgical training (cumulative completed case volume for all
      minor-, medium-, and major-complexity surgeries), (3) research opportunities, and
      (4) working conditions. RESULTS AND LIMITATIONS: Four hundred and seventy-two
      residents completed the online survey (response rate 65%). Surgical training: the
      median number of cumulative completed cases for postgraduate yr (PGY)-5 residents
      was 113 (interquartile range: 76-178). Minor surgeries comprised 57% of all
      surgeries and were performed by residents in all PGYs. Medium-complexity
      surgeries comprised 39% of all surgeries and were mostly performed by residents
      in PGYs 2-5. Major surgeries comprised 4% of all surgeries and were occasionally
      performed by residents in PGYs 3-5. Research opportunities: some 44% have
      attained a medical thesis (Dr. med.), and 39% are currently pursuing research.
      Working conditions: psychosocial work-related stress was high and for 82% of
      residents their effort exceeded their rewards. Some 44% were satisfied, 32% were
      undecided, and 24% were dissatisfied with their current working situation.
      Limitations include self-reported survey answers and a lack of validated
      assessment tools. CONCLUSIONS: Surgical exposure among German urology residents
      is low and comprises minor and medium-complex surgeries. Psychosocial work
      related stress is high for the vast majority of residents indicating the need for
      structural improvements in German urology residency training. PATIENT SUMMARY: In
      this study, we evaluated the surgical training, research opportunities, and
      working conditions among urology residents in Germany. We found low surgical
      exposure and high rates for psychosocial work-related stress, indicating the need
      for structural improvements in German urology residency training.

PMID- 28753834
TI  - Impact of Baseline Characteristics on the Survival Benefit of High-Intensity
      Local Treatment in Metastatic Urothelial Carcinoma of the Bladder.
AB  - A recent study reported an overall survival benefit for patients with metastatic
      urothelial carcinoma of the bladder (mUCB) managed with high-intensity local
      treatment (LT) of the primary tumor (chemotherapy plus radical cystectomy and/or
      radiation therapy >=50Gy). Given the non-negligible morbidity of these
      procedures, adequate patient selection is crucial. Our objective was to identify
      patients who might benefit the most from high-intensity LT. Data for 3044
      patients with mUCB at diagnosis were extracted from the National Cancer Data Base
      2004-2013, and patients were categorized on the basis of treatment: high
      intensity LT versus conservative LT (chemotherapy plus transurethral resection of
      bladder tumor and/or radiation therapy <50Gy). Multivariate Cox regression
      analysis predicted baseline 2-yr overall mortality (OM) risk among patients who
      received conservative LT. We then assessed the interaction between predicted OM
      risk and LT type. Compared to conservative LT, high-intensity LT yielded a higher
      observed OM-free survival rate among all patients with pure mUCB, irrespective of
      their predicted OM risk (nonsignificant interaction, p=0.7). These findings
      underline the need for further retrospective and prospective evaluation. PATIENT
      SUMMARY: Among patients with metastatic histologically pure urothelial carcinoma
      of the bladder, we found an overall survival benefit of high-intensity local
      treatment directed at the primary tumor, regardless of predicted baseline 2-yr
      overall mortality risk.

PMID- 28753835
TI  - Current Evidence of Transurethral En-bloc Resection of Nonmuscle Invasive Bladder
      Cancer.
AB  - CONTEXT: En-bloc resection of bladder tumors (ERBT) is a promising alternative to
      conventional transurethral resection of bladder tumor. OBJECTIVE: To review the
      current results of ERBT. EVIDENCE ACQUISITION: A literature search of articles
      that included the keywords bladder and en bloc was performed on July 15, 2016
      using PubMed/Medline. Relevant English-written original articles were considered.
      Data from the manuscripts were categorized focusing on recent trends on resection
      techniques, specimens' quality, morbidity, and recurrence. EVIDENCE SYNTHESIS:
      ERBT provides high rates of detrusor muscle (> 95%) and specimens of high quality
      for pathological evaluation. It has not been analyzed whether second resections
      can therefore be avoided. All energy devices (lasers, electric cautery) have been
      used to perform ERBT with similar perioperative and oncological results. Data
      show that there is not much difference in respect of perioperative morbidity
      compared with conventional transurethral resection of bladder tumor; however,
      only a few publications used a systematic classification system. No conclusions
      can be drawn regarding the impact of ERBT on recurrence. CONCLUSIONS: The major
      advantage of ERBT is the high rate of detrusor muscle. Based on limited data, no
      significant differences are observed regarding perioperative morbidity and
      recurrence rates. PATIENT SUMMARY: En-bloc resection of bladder tumor is an
      emerging technique aimed at improving quality of surgical specimens. Available
      evidences suggest safety and oncologic equivalence compared with the standard
      transurethral resection of bladder tumor.

PMID- 28753836
TI  - Testosterone Replacement in a Man with Intermediate-risk Prostate Cancer.
AB  - In brief, a hypogonadal man with successfully treated localized prostate cancer
      deserves testosterone therapy (TTh) regardless of grade. The evidence is not
      conclusive but compelling. The story is different for those with intermediate
      risk disease who, for a variety of reasons, need TTh but cannot or elect not to
      have treatment of their primary malignancy, but still desire androgen
      supplementation.

PMID- 28753837
TI  - Absence of Tumor on Repeat Transurethral Resection of Bladder Tumor Does Not
      Predict Final Pathologic T0 Stage in Bladder Cancer Treated with Radical
      Cystectomy.
AB  - BACKGROUND: For patients with bladder cancer (BC) receiving neoadjuvant
      chemotherapy (NAC), complete pathologic absence of tumor (pT0) at radical
      cystectomy (RC) is associated with better survival. It is unclear if pT0 status
      can be attributed to the absence of residual disease (cT0) on transurethral
      resection of bladder tumor (TURBT) or to the effects of NAC. OBJECTIVE: To
      determine how often cT0 is associated with pT0 and identify preoperative and
      postoperative factors associated with survival. DESIGN, SETTING, AND
      PARTICIPANTS: Between 1995 and 2011, 157 out of 1897 RC patients were identified
      as stage cT0 after at least two TURBT procedures at a single center.
      INTERVENTION: RC with or without NAC. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Initial TURBT pathology and clinical staging were reviewed. The primary
      endpoint was pathologic stage at RC. Cox proportional hazards ratios identified
      factors associated with residual disease at RC, overall survival (OS), recurrence
      free survival (RFS), and disease-specific survival (DSS). RESULTS AND
      LIMITATIONS: Of the cT0 patients, 49.7% (n=78) underwent NAC. pT0 was found in
      35.7% (n=56). Residual tumor was found at RC in 63.7% (n=101), of whom 24.8%
      (n=39) had advanced disease (>=pT3 or node-positive disease). Positive lymph
      nodes at RC were found in 12.7% (n=20) of the patients. There was no significant
      difference in achieving pT0 status between patients with and without NAC. The
      presence of advanced BC was most predictive of OS. NAC was associated with longer
      OS and RFS. During median follow-up of 6.3 yr, the 5-yr RFS was 81% for those
      with non-advanced disease and 46% for advanced BC (p<0.001). The 5-yr OS rate was
      77% for non-advanced BC and 46% for invasive BC (p<0.001). Limitations include
      the retrospective design. CONCLUSIONS: Complete TURBT does not predict pT0 at RC.
      A notable fraction of patients with cT0 bladders have locally advanced and/or
      lymph node-positive disease. These findings may be of value when counseling
      patients on bladder preservation strategies for muscle-invasive BC. PATIENT
      SUMMARY: Among patients thought to have had the entire tumor in their bladder
      removed via cystoscopy, a majority have persistent tumors when their bladders
      were removed. In a sizable proportion, these persistent tumors were even more
      invasive than initially thought.

PMID- 28753838
TI  - The EMPaCT Classifier: A Validated Tool to Predict Postoperative Prostate Cancer
      related Death Using Competing-risk Analysis.
AB  - BACKGROUND: Accurate prediction of survival after radical prostatectomy (RP) is
      important for making decisions regarding multimodal therapies. There is a lack of
      tools to predict prostate cancer-related death (PCRD) in patients with high-risk
      features. OBJECTIVE: To develop and validate a prognostic model that predicts
      PCRD combining pathologic features and using competing-risks analysis. DESIGN,
      SETTING, AND PARTICIPANTS: This was a retrospective multi-institutional
      observational cohort study of 5876 patients affected by high-risk prostate
      cancer. Patients were treated using RP and pelvic lymph node dissection (PLND) in
      a multimodal setting, with median follow-up of 49 mo. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: For PCRD prediction, a multivariate model with correction
      for competing risks was constructed to evaluate pathologic high-risk features
      (pT3b-4, Gleason score >=8, and pN1) as predictors of mortality. All possible
      associations of the predictors were combined, and then subgroups with similar
      risk of PCRD were collapsed to obtain a simplified model encoding subgroups with
      significantly differing risk. Eightfold cross-validation of the model was
      performed. RESULTS AND LIMITATIONS: After applying exclusion criteria, 2823
      subjects were identified. pT3b-4, Gleason score >=8, and pN1 were all independent
      predictors of PCRD. The simplified model included the following prognostic
      groups: good prognosis, pN0 with 0-1 additional predictors; intermediate
      prognosis, pN1 with 0-1 additional predictors; poor prognosis, any pN with two
      additional predictors. The cross-validation yielded excellent median model
      accuracy of 88%. The retrospective design and the short follow-up could limit our
      findings. CONCLUSIONS: We developed and validated a novel and easy-to-use
      prognostic instrument to predict PCRD after RP+PLND. This model may allow
      clinicians to correctly counsel patients regarding the intensity of follow-up and
      to tailor adjuvant treatments. PATIENT SUMMARY: Prediction of mortality after
      primary surgery for prostate cancer is important for subsequent treatment plans.
      We present an accurate postoperative model to predict cancer mortality after
      radical prostatectomy for high-risk prostate cancer.

PMID- 28753839
TI  - Role of Restaging Transurethral Resection for T1 Non-muscle invasive Bladder
      Cancer: A Systematic Review and Meta-analysis.
AB  - CONTEXT: Repeat transurethral resection (reTUR) is advocated as a fundamental
      step towards complete clearance and appropriate staging of T1 bladder cancer
      tumors. OBJECTIVE: To assess the impact of reTUR in T1 bladder cancer via a
      systematic review of the literature and meta-analysis of available data sets.
      EVIDENCE ACQUISITION: After definition of the population and of the outcome, a
      systematic search of English language articles in the literature from 1980 to
      2016 was performed. The pooled prevalence of residual tumor and of upstaging at
      reTUR were assessed and computed using a random effects model to take into
      account heterogeneity showed by I2 and Cochran's Q values. A sensitivity analysis
      was conducted to exclude excessive influence by a single study. EVIDENCE
      SYNTHESIS: Among the papers identified, 29 were selected. A total of 3566 and
      2556 cases formed the study population for assessment of the prevalence of
      residual tumor and upstaging, respectively. The corresponding numbers for the
      subgroup with detrusor muscle involvement at the initial TUR were 1565 and 1187.
      The pooled prevalence was 0.56 (95% confidence interval [CI] 0.48-0.63) for
      residual tumor and 0.1 (95% CI 0.06-0.14) for upstaging to T2 at reTUR. The
      corresponding rates for the detrusor muscle subgroup were 0.47 (95% CI 0.33-0.62)
      and 0.1 (95% CI 0.06-0.14). The sensitivity analysis excluded an excessive
      influence of each of the studies examined. CONCLUSIONS: Pooled prevalence rates
      for residual tumor (~50%) and upstaging to invasive disease (10%) at reTUR in T1
      cases were high, and were stable among studies in different decades and for cases
      with detrusor muscle involvement at the initial TUR. Therefore, reTUR remains a
      fundamental procedure. PATIENT SUMMARY: Repeat transurethral resection after a
      diagnosis of stage T1 bladder cancer is recommended given the high risk of
      misallocation to the proper treatment.

PMID- 28753840
TI  - Caveolin-1 Expression in Upper Tract Urothelial Carcinoma.
AB  - BACKGROUND: Improvement in postoperative risk stratification of upper tract
      urothelial carcinoma (UTUC) is required to better predict outcomes and counsel
      patients on adjuvant treatment. OBJECTIVE: To validate the association between
      caveolin-1 and oncological outcomes in patients treated with radical
      nephroureterectomy (RNU) for UTUC. DESIGN, SETTING, AND PARTICIPANTS: Caveolin-1
      expression was evaluated via immunochemistry on a tissue microarray from 621
      patients. Caveolin-1 was considered overexpressed when at least 50% of the tumor
      cells stained positive. The median follow-up in this retrospective study was 35
      mo (interquartile range 16-65). INTERVENTION: Radical nephroureterectomy. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Univariate and multivariable Cox
      proportional hazards regression models were used to assess the association
      between caveolin-1 expression and recurrence and cancer-specific mortality (CSM).
      RESULTS AND LIMITATIONS: Caveolin-1 was overexpressed in 150 patients (24%).
      Overexpression was associated with higher pathological stage (p<0.001) and grade
      (p<0.001). In univariate analyses, overexpression of caveolin-1 was significantly
      associated with lower recurrence (hazard ratio [HR] 1.7, 95% confidence interval
      [CI] 1.2-2.6; p=0.004) and CSM (HR 1.8, 95% CI 1.2-2.7; p=0.005); however,
      multivariable analyses did not prove its independent association with outcomes.
      The study is limited by its retrospective nature. CONCLUSIONS: Despite
      overexpression in a quarter of UTUC patients, caveolin-1 was not independently
      associated with oncological outcomes. Its use could be evaluated to improve
      clinical staging of biopsy specimens and to help in clinical decision-making
      regarding a kidney-sparing approach or neoadjuvant systemic treatment. PATIENT
      SUMMARY: Development of a panel of prognostic and predictive markers is mandatory
      for patient consultations in the era of personalized medicine. We evaluated the
      role of caveolin-1 in a large series of patients treated with radical
      nephroureterectomy for upper tract urothelial carcinoma (UTUC) and found that it
      was not independently associated with oncological outcomes. Nevertheless, it was
      associated with adverse pathological features. Considering caveolin-1 in UTUC
      biopsy specimens could help in improving clinical staging and decision-making
      regarding a kidney-sparing approach or neoadjuvant systemic treatment.

PMID- 28753841
TI  - Case Presentation: Neurogenic Bladder in a Girl After Surgery for Cloacal
      Malformation.
AB  - A girl born in 2006 has been under close surveillance in our pediatric urology
      unit since birth. Besides cloacal malformation, she has associated spinal cord
      dysraphism, uterus didelphys, and a vaginal septum.

PMID- 28753842
TI  - Molecular and Genomic Profiling to Identify Actionable Targets in Chromophobe
      Renal Cell Cancer.
AB  - : Metastatic chromophobe renal cell cancer (chRCC) is a rare subtype of RCC with
      no standard treatment. We performed molecular profiling of 12 chRCC cases to
      identify alterations predictive of response to therapy. Tests included
      immunohistochemistry assays, fluorescence in situ hybridization, and next
      generation sequencing. Analysis identified c-KIT overexpression in 6/9 (67%)
      samples analyzed, and loss of protein expression of RRM1 and MGMT in 11/12 (92%)
      and of PTEN in 7/12 samples (58%). Mutations of TP53, PTEN, APC, and VHL genes
      were identified. In summary, molecular profiling of chRCC identified alterations
      in genes and protein expression that might provide a mechanistic rationale for
      off-label use of approved therapies in advanced chRCC, and could guide the design
      of molecularly targeted clinical trials. PATIENT SUMMARY: In this study, we
      evaluated samples of a rare type of kidney cancer (chromophobe type) and
      identified potential genetic markers that could be used to individualize
      treatment and possibly improve treatment outcomes.

PMID- 28753843
TI  - Prognostic Value of Androgen Receptor Splice Variant 7 in the Treatment of
      Castration-resistant Prostate Cancer with Next generation Androgen Receptor
      Signal Inhibition: A Systematic Review and Meta-analysis.
AB  - CONTEXT: Androgen receptor splice variant 7 (AR-V7) may be associated with
      resistance to next-generation androgen receptor signaling (ARS) inhibitors in
      castration-resistant prostate cancer (CRPC) sensitive to chemotherapy. OBJECTIVE:
      To evaluate the prognostic value of AR-V7 for prostate specific antigen (PSA)
      response, progression-free survival (PFS), and overall survival (OS) among CRPC
      patients treated with ARS inhibitors or chemotherapy. EVIDENCE ACQUISITION: A
      search of PubMed, Embase, and Web of Science databases was performed using the
      keywords "prostate cancer", "prostate tumor", "prostate neoplasm", "prostate
      carcinoma"; "AR-V7", "AR3", "androgen receptor splicing variant-7" and "androgen
      receptor-3". Fourteen trials published up to August 2016 were selected. EVIDENCE
      SYNTHESIS: A significantly greater proportion of CRPCs than newly diagnosed
      prostate cancers were AR-V7-positive (odds ratio [OR] 8.29, 95% confidence
      interval [CI] 5.06-13.57; p<0.001). AR-V7-positive patients treated with ARS
      inhibitors had a significantly lower PSA response than those who were AR-V7
      negative (OR 0.05, 95% CI 0.02-0.16; p<0.001).The difference was not significant
      in chemotherapy-treated patients (OR 0.64, 95% CI 0.3-1.33; p=0.23). Both PFS
      (hazard ratio [HR] 4.05, 95% CI 1.91-8.59; p=0.0003) and OS (HR 4.79, 95% CI 2.14
      10.72; p<0.001) were better in AR-V7-negative than AR-V7-positive CRPC patients
      treated with ARS inhibitors. In chemotherapy patients, AR-V7 status had no
      significant effect on PFS (HR 1.26, 95% CI 0.80-2.00; p=0.32).However, AR-V7
      negative patients had significantly better OS (HR 2.82, 95% CI 1.72-4.62;
      p<0.001). The limitations of our meta-analysis were differences in study sample
      size and design, AR-V7 assay, and disease characteristics. CONCLUSIONS: AR-V7
      positivity was associated with poorer PSA response and PFS prognosis in CRPC
      patients treated with ARS inhibitors, but did not affect outcomes except OS for
      those treated with chemotherapy. Additional studies are warranted to confirm
      these findings. PATIENT SUMMARY: We concluded from several studies that androgen
      receptor splice variant 7 (AR-V7) could predict the outcomes of prostate cancer.
      AR-V7-positive patients have poorer outcomes when treated with abiraterone or
      enzalutamide, but relatively better outcomes when treated by chemotherapy.

PMID- 28753844
TI  - Transcriptome Wide Analysis of Magnetic Resonance Imaging-targeted Biopsy and
      Matching Surgical Specimens from High-risk Prostate Cancer Patients Treated with
      Radical Prostatectomy: The Target Must Be Hit.
AB  - BACKGROUND: The most suspicious lesions on multiparametric magnetic resonance
      imaging (MRI) may be representative of final pathology. OBJECTIVE: We connect
      imaging with high-precision spatial annotation of biopsies and genomic cancer
      signatures to compare the genomic signals of the index lesion and biopsy cores of
      adjacent and far away locations. DESIGN, SETTING, AND PARTICIPANTS: Eleven
      patients diagnosed with high-risk prostate cancer on MRI/transrectal ultrasound
      fusion biopsy (Bx) and treated with radical prostatectomy (RP). Five tissue
      specimens were collected from each patient. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Whole transcriptome RNA-expression was profiled for each sample.
      Genomic signatures were used to compare signals in MRI invisible versus visible
      foci using Pearson's correlation and to assess intratumoral heterogeneity using
      hierarchical clustering. RESULTS AND LIMITATIONS: Ten RP and 27 Bx-samples passed
      quality control. Gene expression between RP and index Bx, but not adjacent benign
      samples, was highly correlated. Genomic Gleason grade classifier features
      measured across the different samples showed concordant expression across Bx and
      RP tumor samples, while an inverse expression pattern was observed between tumor
      and benign samples indicating the lack of a strong field-effect. The distribution
      of low and high Prostate Imaging Reporting and Data System (PI-RADS) samples was
      10 and 11, respectively. Genomics of all low PI-RADS samples resembled benign
      tissue and most high PI-RADS samples resembled cancer tissue. A strong
      association was observed between PI-RADS version 2 and Decipher as well as the
      genomic Gleason grade classifier score. Clustering analysis showed that most
      samples cluster tightly by patient. One patient showed unique tumor biology in
      index versus secondary lesion suggesting the presence of intrapatient
      heterogeneity and the utility in profiling multiple foci identified by MRI.
      CONCLUSIONS: MRI-targeted Bx-genomics show excellent correlation with RP-genomics
      and confirm the information captured by PI-RADS. Sampling of the target lesion
      must be precise as correlation between index and benign lesions was not seen.
      PATIENT SUMMARY: In this report, we tested if targeted prostate sampling using
      magnetic resonance imaging-fusion biopsy allows to genetically describe index
      tumors of prostate cancer. We found that imaging genomics correlated well with
      final prostatectomy provided that the target is hit precisely.

PMID- 28753845
TI  - Variability of Sex Disparities in Cancer Incidence over 30 Years: The Striking
      Case of Kidney Cancer.
AB  - It is well established that men are at higher risk of most non-sex-specific
      cancers than women, but there has been surprisingly little research investigating
      these differences. This is possibly because differences in exposure to
      established risk factors and hypothesised protection by female sex hormones are
      thought to account for the totality of the sex differences. These explanations
      remain somewhat speculative, as the magnitude of the sex ratio in cancer
      incidence has not been systematically studied, with no quantitative estimate of
      the variability of the sex ratio across countries, age groups, and periods of
      diagnosis. We analysed worldwide cancer incidence data for the years 1978-2007 in
      terms of sex disparities, and explicitly quantified the variability in sex
      disparities by age, year, and geographical region. Our analysis highlights
      several cancer types for which suspected and commonly accepted factors are
      unlikely to fully explain the observed sex disparity. In particular, kidney
      cancer showed a 2:1 male/female case incidence ratio that was constant by age,
      year, and region, suggesting that factors other than sociocultural habits and
      health behaviours are responsible for this sex disparity. PATIENT SUMMARY: We
      quantified the difference in the incidence of various cancer types between men
      and women across the world over 30 years. While the trends for some cancers such
      as lung cancer are clearly correlated with known variations in lifestyle habits,
      we found that the sex disparity observed for others such as kidney cancer is
      unlikely to be explained by known risk factors.

PMID- 28753846
TI  - The Landscape of Whole-genome Alterations and Pathologic Features in
      Genitourinary Malignancies: An Analysis of the Cancer Genome Atlas.
AB  - BACKGROUND: The accumulation of somatic genetic alterations drives
      carcinogenesis. Little is known, however, about how the level of genetic
      alteration across an entire cancer genome affects tumor grade, stage or survival.
      OBJECTIVE: To investigate the influence of somatic mutation count (MC) and copy
      number variation (CNV) on pathologic and oncologic outcomes in patients with
      genitourinary malignancies in The Cancer Genome Atlas (TCGA). DESIGN, SETTING,
      AND PARTICIPANTS: TCGA data sets for adrenocortical carcinoma (ACC), bladder
      urothelial carcinoma (BLCA), chromophobe renal cell carcinoma (RCC; KICH), clear
      cell RCC (KIRC), papillary RCC (KIRP), pheochromocytoma and paraganglioma (PCPG),
      prostate adenocarcinoma (PRAD), and testis germ cell tumor (TGCT) were accessed
      via cBioportal. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Median MC and CNV
      were compared among and within each tumor type. Patients were stratified by grade
      and stage, and differences in MC and CNV were compared. Correlation of MC and CNV
      with overall survival (OS) and recurrence-free survival (RFS) was analyzed when
      these data were available. RESULTS AND LIMITATIONS: Among the tumor types
      analyzed, BLCA had the highest MC at 167, followed by ACC (89), KIRP (71), TGCT
      (55), KIRC (45), PRAD (34), PCPG (14), and KICH (12). The tumor type with the
      highest fraction of the genome with CNV was KICH (0.94), followed by ACC (0.58),
      TGCT (0.41), BLCA (0.29), KIRP (0.15), PCPG (0.13), KIRC (0.12), and PRAD (0.06).
      MC was associated with higher T stage in ACC, N stage in KIRC, M stage in ACC,
      grade in BLCA, and primary Gleason score in PRAD, and was associated with OS and
      RFS in KICH. CNV was associated with higher N stage in PRAD, grade in KIRC, and
      Gleason grade in PRAD. In addition, higher CNV was independently associated with
      inferior RFS for KIRC, as well as inferior OS and RFS for KIRP. CONCLUSIONS: MC
      and CNV vary greatly among tumor types. PATIENT SUMMARY: Cancers with higher
      levels of genomic alterations are associated with worse pathologic features and
      survival. The degree of genomic alterations could serve as a useful marker of
      disease aggressiveness.

PMID- 28753847
TI  - Incidence, Risk Factors, Management, and Complications of Rectal Injuries During
      Radical Prostatectomy.
AB  - Rectal injury (RI) during radical prostatectomy (RP) is a severe complication. So
      far, only limited data describing the incidence, risk factors, management, and
      complications of RI are available. In an analysis of data for 24178 patients, we
      identified 113/24076 patients (0.47%) undergoing open or robotic RP and 7/102
      patients (6.86%) after salvage RP who experienced an RI. Besides salvage RP,
      local tumor stage, Gleason grade, lymph node status, and surgical experience, but
      not surgical approach (robotic vs open), could be identified as risk factors for
      RI in univariate and multivariate analysis. Intraoperative management of RI
      comprised closure with two to three layers. In 13/109 patients (11.9%), a
      diverting colostomy/ileostomy was carried out. Some 12% of men with closure of an
      RI developed a recto-anastomosis fistula, and 57% of those who had an additional
      diverting enterostomy. Thus, the overall incidence of recto-anastomosis fistula
      after RP was <0.1%. The extent of rectal laceration, prior radiation, and
      intraoperative signs of rectal infiltration were associated with the development
      of a subsequent recto-anastomosis fistula. Some 83% of patients with a recto
      anastomosis fistula needed further intervention. PATIENT SUMMARY: We analyzed the
      incidence, risk factors, management, and complications of rectal injury during
      radical prostatectomy. Overall, the incidence of rectal injury and subsequent
      development of recto-anastomosis fistulas is low unless the patient has
      significant risk factors.

PMID- 28753848
TI  - Impact of Microscopic Wall Invasion of the Renal Vein or Inferior Vena Cava on
      Cancer-specific Survival in Patients with Renal Cell Carcinoma and Tumor
      Thrombus: A Multi-institutional Analysis from the International Renal Cell
      Carcinoma-Venous Thrombus Consortium.
AB  - BACKGROUND: Microscopic vein invasion (MVI), with local destruction and invasion
      of the endothelium by tumor, is of controversial predictive value in renal cell
      carcinoma (RCC). OBJECTIVE: To assess the impact of venous extension and wall
      invasion in RCC on survival. DESIGN, SETTING, AND PARTICIPANTS: Data for 1023 RCC
      patients with vena cava thrombus treated with radical nephrectomy and complete
      tumor thrombectomy were collected within a prospectively maintained international
      consortium (1995-2012). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Kaplan
      Meier method and univariable and multivariable Cox regression analyses were used
      to assess the impact of MVI on cancer-specific survival (CSS). The main two
      variables of interest were microscopic renal vein wall invasion (MRVI) and
      microscopic vena cava wall invasion (MVCI). RESULTS: MRVI was found in 725 cases
      (70.9%) and MVCI in 230 (22.5%). Patients with MRVI had larger tumors (p=0.005),
      longer hospital stay (p<0.001), higher clinical stage 0.039), higher Fuhrman
      grade (p=0.028), and more frequent fat invasion. Presence of MVCI was associated
      with larger tumors (p<0.001), longer hospital stay (p<0.001), higher clinical
      stage (p<0.001), lymph node involvement (p=0.045), higher Fuhrman grade
      (p<0.001), and higher thrombus level (p<0.001). With median follow-up of 52 mo,
      overall 5-yr CSS was 57.4%. Multivariable analysis showed that presence of MRVI
      was an independent factor related to CSS (hazard ratio 2.24, 95% confidence
      interval 1.24-3.59, p=0.006). The main limitation was the inability to report MVI
      percentages. CONCLUSIONS: Patients with MRVI experience significantly worse
      survival outcomes after radical nephrectomy and tumor thrombectomy. Consideration
      of MRVI at final pathology is appropriate to improve decision-making for risk
      adapted follow-up. PATIENT SUMMARY: The behavior of locally advanced renal cell
      carcinoma (RCC) depends on clinical and pathologic factors. Analysis revealed
      that RCC patients with microscopic renal vein wall invasion experience
      significantly worse cancer-specific survival.

PMID- 28753849
TI  - Safety and Antitumour Activity of ODM-201 (BAY-1841788) in Castration-resistant,
      CYP17 Inhibitor-naive Prostate Cancer: Results from Extended Follow-up of the
      ARADES Trial.
AB  - BACKGROUND: Patients with castration-resistant prostate cancer (CRPC) had
      extended responses to the androgen receptor antagonist ODM-201, in phase 1/2
      studies. OBJECTIVE: To evaluate the safety and antitumour activity of prolonged
      ODM-201 treatment in patients with CRPC. DESIGN, SETTING, AND PARTICIPANTS: The
      ARADES trial was a multicentre phase 1 (dose escalation) and phase 2 (dose
      expansion) trial; 134 patients with CRPC were stratified by previous chemotherapy
      to receive ODM-201. This paper reports extended follow-up in CYP17 inhibitor
      (CYP17i)-naive patients. INTERVENTION: Patients (n=77) received oral ODM-201
      twice daily at daily doses of 200-1800mg. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Safety, measured as the occurrence of adverse events (AEs), prostate
      specific antigen (PSA), and radiographic progression. RESULTS AND LIMITATIONS:
      The safety profile of extended ODM-201 treatment (median treatment duration 8.2
      mo, 95% confidence interval [CI] 5.6-11.0) was consistent with that reported at
      the time of the original data cutoff in the main ARADES trial, with no unexpected
      safety concerns over time. The majority of AEs (61.1%) were mild (grade 1); the
      most common AE was fatigue/asthenia (35.1% of patients), with no clear
      relationship to ODM-201. Median time to PSA progression was 25.2 mo (95% CI 11.3
      25.2) for chemotherapy-naive men and not reached (NR; 95% CI 5.5-NR) for
      chemotherapy-pretreated patients; a trend for improved antitumour response was
      observed for chemotherapy-naive patients. The median time to radiographic
      progression was longer for chemotherapy-naive (14.0 mo, 95% CI 8.1-33.3) than for
      chemotherapy-pretreated (7.2 mo, 95% CI 2.7-11.0) patients. CONCLUSIONS:
      Prolonged exposure to ODM-201 was well tolerated, with no additional safety
      concerns; disease suppression was sustained, especially in chemotherapy-naive
      patients. These data support further development of ODM-201 in men with CYP17i
      naive CRPC. PATIENT SUMMARY: Extended ODM-201 therapy was well tolerated, with
      beneficial antitumour activity in men with advanced prostate cancer, indicating
      that ODM-201 may represent a new active treatment for men with CRPC. This
      extension trial is registered at ClinicalTrials.gov (www.clinicaltrials.gov)
      under identification number NCT01429064.

PMID- 28753850
TI  - Detection of Prostate Cancer Using a Multistep Approach with Prostate-specific
      Antigen, the Stockholm 3 Test, and Targeted Biopsies: The STHLM3 MRI Project.
AB  - There is a distinct need for clinical improvements to the pipeline for prostate
      detection. The aim of the STHLM3 magnetic resonance imaging (MRI) study is to
      provide evidence of an improved and structured multistep pipeline for prostate
      cancer detection using the bloodbased Stockholm 3 test and MRI to achieve better
      specificity and reduce the risk of overdiagnosis.

PMID- 28753851
TI  - Safety and Antitumour Activity of ODM-201 (BAY-1841788) in Chemotherapy-naive and
      CYP17 Inhibitor-naive Patients: Follow-up from the ARADES and ARAFOR Trials.
AB  - BACKGROUND: ODM-201, a new androgen receptor antagonist for treatment of
      metastatic castration-resistant prostate cancer (mCRPC), demonstrated antitumour
      activity and acceptable tolerability in phase 1/2 trials. OBJECTIVE: To determine
      the antitumour activity and safety profile of extended treatment with ODM-201 in
      men with mCRPC. DESIGN, SETTING, AND PARTICIPANTS: ARADES and ARAFOR trials with
      ODM-201 enrolled chemotherapy-naive and CYP17 inhibitor (CYP17i)-naive mCRPC
      patients. Both trials had extended follow-up. Here we report results for
      chemotherapy-naive and CYP17i-naive patients from both trials (data cutoff
      October 2014 for ARADES and April 2015 for ARAFOR) after extended follow-up.
      INTERVENTION: A total of 41 chemotherapy-naive and CYP17i-naive patients received
      oral ODM-201 twice daily (total daily dose of 1200, 1400 or 1800mg). OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Antitumour activity was assessed in terms
      of prostate-specific antigen (PSA) declines and PSA/radiographic progression.
      Safety was assessed until disease progression and/or drug discontinuation due to
      any intolerable adverse event (AE). RESULTS AND LIMITATIONS: ODM-201 safety data
      after a median treatment time of 13.5 mo (95% confidence interval [CI] 9.7-15.6,
      interquartile range [IQR] 7.5-22.0) were similar to those reported in the main
      ARADES and ARAFOR trials. The overall AE incidence was 80.5% (n=33/41), with
      58.5% (n=24/41) of patients experiencing only grade 1-2 AEs. The most common AEs
      were fatigue, back pain, diarrhoea, nausea, and pain in extremity. The median
      times to PSA and radiological progression were 12.4 mo (95% CI 6.3-18.2, IQR 5.5
      22.0) and 15.3 mo (95% CI 9.5-not reached [NR], IQR 6.3-NR), respectively.
      CONCLUSIONS: Extended treatment with ODM-201 (1200-1800mg/d) was well tolerated,
      with no new safety concerns, and provided evidence of sustained antitumour
      activity in chemotherapy-naive and CYP17i-naive patients with mCRPC. PATIENT
      SUMMARY: Prolonged treatment with high doses of ODM-201 was well tolerated and
      provided long-lasting disease control in patients with mCRPC. ODM-201 represents
      a therapeutic treatment option for mCRPC. The ARAFOR trial (including the follow
      up stage) and the follow-up component of the ARADES trial are registered with
      ClinicalTrials.gov as trial numbers NCT01784757 and NCT01429064.

PMID- 28753852
TI  - DESNT: A Poor Prognosis Category of Human Prostate Cancer.
AB  - BACKGROUND: A critical problem in the clinical management of prostate cancer is
      that it is highly heterogeneous. Accurate prediction of individual cancer
      behaviour is therefore not achievable at the time of diagnosis leading to
      substantial overtreatment. It remains an enigma that, in contrast to breast
      cancer, unsupervised analyses of global expression profiles have not currently
      defined robust categories of prostate cancer with distinct clinical outcomes.
      OBJECTIVE: To devise a novel classification framework for human prostate cancer
      based on unsupervised mathematical approaches. DESIGN, SETTING, AND PARTICIPANTS:
      Our analyses are based on the hypothesis that previous attempts to classify
      prostate cancer have been unsuccessful because individual samples of prostate
      cancer frequently have heterogeneous compositions. To address this issue, we
      applied an unsupervised Bayesian procedure called Latent Process Decomposition to
      four independent prostate cancer transcriptome datasets obtained using samples
      from prostatectomy patients and containing between 78 and 182 participants.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical failure was assessed
      using log-rank analysis and Cox regression analysis. RESULTS AND LIMITATIONS:
      Application of Latent Process Decomposition identified a common process in all
      four independent datasets examined. Cancers assigned to this process (designated
      DESNT cancers) are characterized by low expression of a core set of 45 genes,
      many encoding proteins involved in the cytoskeleton machinery, ion transport, and
      cell adhesion. For the three datasets with linked prostate-specific antigen
      failure data following prostatectomy, patients with DESNT cancer exhibited poor
      outcome relative to other patients (p=2.65*10-5, p=4.28*10-5, and p=2.98*10-8).
      When these three datasets were combined the independent predictive value of DESNT
      membership was p=1.61*10-7 compared with p=1.00*10-5 for Gleason sum. A
      limitation of the study is that only prediction of prostate-specific antigen
      failure was examined. CONCLUSIONS: Our results demonstrate the existence of a
      novel poor prognosis category of human prostate cancer and will assist in the
      targeting of therapy, helping avoid treatment-associated morbidity in men with
      indolent disease. PATIENT SUMMARY: Prostate cancer, unlike breast cancer, does
      not have a robust classification framework. We propose that this failure has
      occurred because prostate cancer samples selected for analysis frequently have
      heterozygous compositions (individual samples are made up of many different parts
      that each have different characteristics). Applying a mathematical approach that
      can overcome this problem we identify a novel poor prognosis category of human
      prostate cancer called DESNT.

PMID- 28753853
TI  - Survival Outcomes in Octogenarian and Nonagenarian Patients Treated with First
      line Androgen Deprivation Therapy for Organ-confined Prostate Cancer.
AB  - BACKGROUND: The use of primary androgen deprivation therapy (PADT) is common in
      elderly men with early-stage prostate cancer (PCa), despite the absence of
      guideline recommendations. OBJECTIVE: To examine survival patterns of octo- and
      nonagenarian men with organ-confined PCa exposed to PADT, to assess whether their
      life expectancy warrants androgen deprivation therapy use. DESIGN, SETTING, AND
      PARTICIPANTS: In the Surveillance, Epidemiology, and End Results-Medicare-linked
      database, we identified 14 785 octo- and nonagenarian organ-confined PCa patients
      treated with PADT between 1991 and 2009. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: The smoothed cumulative incidence method was used to examine 10-yr
      overall mortality, cancer-specific mortality (CSM), and other-cause mortality
      (OCM) rates. Multivariable Cox regression analyses focused on the combined effect
      of age and Charlson comorbidity index (CCI) after adjusting for different
      confounders. RESULTS AND LIMITATIONS: Of all the deaths observed during the study
      period, 80% were due to non-cancer causes and 20% were due to PCa. The 10-yr
      overall survival (OS) rate in the overall population was 15.4%. The 10-yr OS
      rates ranged from 19.9% in patients aged 80-84 yr to 3.1% in those aged >=90 yr.
      Similarly, the 10-yr OS rates ranged from 18.7% in patients with CCI=0 to 11.5%
      in those with CCI>=2. The 10-yr OCM rate in the overall population was 68.2%. The
      10-yr OCM rates ranged from 64.6% in patients aged 80-84 yr to 77.2% in patients
      aged >=90 yr. Similarly, the 10-yr OCM rates ranged from 62.1% in patients with
      CCI=0 to 75.2% in those with CCI>=2. The 10-yr CSM rate in the overall population
      was 16.4%. The 10-yr CSM rates ranged from 15.5% in patients aged 80-84 yr to
      19.7% in those aged >=90 yr, and from 19.2% in patients with CCI=0 to 13.3% in
      those with CCI>=2. CONCLUSIONS: Of the elderly patients with organ-confined PCa
      exposed to PADT, only 15% survive at 10-yr follow-up. Mortality related to non
      cancer causes is the leading cause of death in the same follow-up period. These
      figures question the rationale for PADT in elderly men with organ-confined PCa.
      PATIENT SUMMARY: In this study, we looked at the survival patterns of octo- and
      nonagenarians treated with primary androgen deprivation therapy for organ
      confined prostate cancer. We found that a small proportion of patients who
      received primary androgen deprivation therapy remain alive at 10-yr follow-up,
      and the leading cause of death was not attributable to prostate cancer.

PMID- 28753854
TI  - Peri-prostatic Fat Volume Measurement as a Predictive Tool for Castration
      Resistance in Advanced Prostate Cancer.
AB  - BACKGROUND: Obesity and aggressive prostate cancer (PC) may be linked, but how
      local peri-prostatic fat relates to tumour response following androgen
      deprivation therapy (ADT) is unknown. OBJECTIVE: To test if peri-prostatic fat
      volume (PPFV) predicts tumour response to ADT. DESIGN, SETTING, AND PARTICIPANTS:
      We performed a retrospective study on consecutive patients receiving primary ADT.
      From staging pelvic magnetic resonance imaging scans, the PPFV was quantified
      with OsirixX 6.5 imaging software. Statistical (univariate and multivariate)
      analysis were performed using R Version 3.2.1. RESULTS AND LIMITATIONS: Of 224
      consecutive patients, 61 with advanced (>=T3 or N1 or M1) disease had (3-mm high
      resolution axial sections) pelvic magnetic resonance imaging scan before ADT.
      Median age=75 yr; median PPFV=24.8cm3 (range, 7.4-139.4cm3). PPFV was
      significantly higher in patients who developed castration resistant prostate
      cancer (CRPC; n=31), with a median of 37.9cm3 compared with 16.1cm3 (p <0.0001,
      Wilcoxon rank sum test) in patients who showed sustained response to ADT (n=30).
      Multivariate analysis using Cox proportional hazards models were performed
      controlling for known predictors of CRPC. PPFV was shown to be independent of all
      included factors, and the most significant predictor of time to CRPC. Using our
      multivariate model consisting of all known factors prior to ADT, PPFV
      significantly improved the area under the curve of the multivariate models
      receiver operating characteristic analysis. The main study limitation is a
      relatively small cohort to account for multiple variables, necessitating a future
      large-scale prospective analysis of PPFV in advanced PC. CONCLUSIONS: PPFV
      quantification in patients with advanced PC predicts tumour response to ADT.
      PATIENT SUMMARY: The amount of fat around the prostate predicts prostate cancer
      response to hormone treatment.

PMID- 28753855
TI  - Ischemia and Functional Recovery from Partial Nephrectomy: Refined Perspectives.
AB  - BACKGROUND: Nephron mass preservation is a key determinant of functional outcomes
      after partial nephrectomy (PN), while ischemia plays a secondary role. Analyses
      focused specifically on recovery of the operated kidney appear to be most
      informative, yet have only included limited numbers of patients. OBJECTIVE: To
      evaluate the relative impact of parenchymal preservation and ischemia on
      functional recovery after PN using a more robust cohort allowing for more refined
      perspectives about ischemia. DESIGN, SETTING, AND PARTICIPANTS: A total of 401
      patients managed with PN with necessary studies were analyzed for function and
      nephron mass preserved specifically within the kidney exposed to ischemia.
      INTERVENTION: PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The nephron mass
      preserved was measured from computed tomography scans <2 mo before and 3-12 mo
      after PN. Patients with two kidneys were required to have nuclear renal scans
      within the same timeframes. Recovery from ischemia was defined as the percent
      function preserved normalized by the percent nephron mass preserved. Pearson
      correlation was used to evaluate relationships between functional recovery and
      nephron mass preservation or ischemia time. Multivariable linear regression
      assessed predictors for recovery from ischemia. RESULTS AND LIMITATIONS: The
      median tumor size was 3.5cm and the median RENAL score was 8. Cold and warm
      ischemia were utilized in 151 and 250 patients, and the median ischemia time was
      27 and 21min, respectively. The function preserved was strongly correlated with
      nephron mass preserved(r=0.63; p<0.001). Median recovery from ischemia was
      significantly higher for hypothermia (99% vs 92%; p<0.001) and remained
      consistently strong even with longer duration. Multivariable analysis
      demonstrated that recovery from ischemia, which normalizes for nephron mass
      preservation, was significantly associated with ischemia type and duration (both
      p<0.05). However, each additional 10min of warm ischemia was associated with only
      a 2.5% decline in recovery from ischemia. Limitations include the retrospective
      design. CONCLUSIONS: Our data suggest that functional recovery from clamped PN is
      most reliable with hypothermia. Longer intervals of warm ischemia are associates
      with reduced recovery; however, incremental changes are modest and may not be
      clinically significant in patients with a normal contralateral kidney. PATIENT
      SUMMARY: Functional recovery after clamped partial nephrectomy is primarily
      dependent on preservation of nephron mass. Recovery is most reliable when
      hypothermia is applied. Longer intervals of warm ischemia are associated with
      reduced recovery; however, the incremental changes are modest.

PMID- 28753856
TI  - Trends in Prostate-Specific Antigen Screening Since the Implementation of the
      2012 US Preventive Services Task Force Recommendations.
AB  - In 2012, the US Preventive Services Task Force recommended against prostate
      specific antigen (PSA) screening. Following the initial decrease in PSA screening
      rate, there appears to be no further decrease in screening rate from 2013 to
      2015. In addition, the screening rate did not differ by age or race.

PMID- 28753857
TI  - The Impact of Plasmacytoid Variant Histology on the Survival of Patients with
      Urothelial Carcinoma of Bladder after Radical Cystectomy.
AB  - BACKGROUND: The clinical significance of the plasmacytoid variant (PCV) in
      urothelial carcinoma (UC) is currently lacking. OBJECTIVE: To compare clinical
      outcomes of patients with any PCV with that of patients with pure UC treated with
      radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS: We identified 98
      patients who had pathologically confirmed PCV UC and 1312 patients with pure UC
      and no variant history who underwent RC at our institution between 1995 and 2014.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox
      regression and Cox proportional hazards regression to determine if PCV was
      associated with overall survival (OS). RESULTS AND LIMITATIONS: Patients with PCV
      UC were more likely to have advanced tumor stage (p=0.001), positive lymph nodes
      (p=0.038), and receive neoadjuvant chemotherapy than those with pure UC (46% vs
      22%, p<0.0001). The rate of positive soft tissue surgical margins was over five
      times greater in the PCV UC group compared with the pure UC group (21% vs 4.1%,
      respectively, p<0.0001). Median OS for the pure UC versus the PCV patients were 8
      yr and 3.8 yr, respectively. On univariable analysis, PCV was associated with an
      increased risk of overall mortality (hazard ratio=1.34, 95% confidence interval:
      1.02-1.78, p=0.039). However, on multivariable analysis adjusted for age, sex,
      neoadjuvant chemotherapy received, lymph node status, pathologic stage, and soft
      margin status, the association between PCV and OS was no longer significant
      (hazard ratio=1.06, 95% confidence interval: 0.78, 1.43, p=0.7). This
      retrospective study is limited by the lack of pathological reanalysis, and the
      impact of other concurrent mixed histology cannot be determined in this study.
      CONCLUSIONS: Patients with PCV features have a higher disease burden at RC
      compared with those with pure UC. However, PCV was not an independent predictor
      of survival after RC on multivariable analysis, suggesting that PCV histology
      should not be used as an independent prognostic factor. PATIENT SUMMARY:
      Plasmacytoid urothelial carcinoma is a rare and aggressive form of bladder
      cancer. Patients with plasmacytoid urothelial carcinoma had worse adverse
      pathologic features, but this was not associated with worse overall mortality
      when compared with patients with pure urothelial carcinoma.

PMID- 28753858
TI  - Correlation Between Primary Hypospadias Repair and Subsequent Urethral Strictures
      in a Series of 408 Adult Patients.
AB  - BACKGROUND: The correlation between primary hypospadias repair and subsequent
      urethral strictures in adults has never been addressed. OBJECTIVE: To evaluate
      the correlation between the site of primary hypospadias repair and the site of
      subsequent strictures and to investigate the predictive factors of failure after
      urethroplasty. DESIGN, SETTING, AND PARTICIPANTS: An observational,
      retrospective, descriptive study of adult patients with urethral strictures
      following hypospadias surgery was carried out in a single centre. INTERVENTION:
      Meatotomy, meatoplasty, end-to-end anastomosis, urethroplasty, perineostomy,
      urethrotomy, and fistula closure. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      We performed correlations between the site of primary hypospadias and the site of
      subsequent strictures, treatment failure, and patient lack of motivation for
      definitive treatment. Cross-tables, Kaplan-Meier curves, and logistic or Cox
      regression were used. RESULTS AND LIMITATIONS: A total of 408 patients, with
      median follow-up of 96 mo, were included. Concordance between the site of primary
      hypospadias repair and the site of subsequent strictures was observed.
      Multivariable analysis revealed that the number of previous operations needed for
      initial hypospadias repair was not associated with the risk of treatment failure
      (hazard ratio [HR] 0.96; 95% confidence Interval [CI] 0.88-1.04; p=0.3) or a lack
      of patient motivation (odds ratio 0.99, 95% CI 0.90-1.10; p=0.9). Length of
      stenosis (HR 1.38, 95% CI 1.11-1.71; p=0.004) and lichen sclerosus (HR 1.73, 95%
      CI 1.03-3.25; p=0.035) were associated with a higher risk of treatment failure.
      Our study is not representative of the entire population of patients with
      hypospadias repair. CONCLUSIONS: The stricture site is usually consistent with
      the site of hypospadias. Stricture length, but not the number of previous
      operations needed for primary hypospadias repair, was associated with the risk of
      failure. PATIENT SUMMARY: The number of operations needed for hypospadias repair
      was not associated with failure of subsequent urethroplasty.

PMID- 28753859
TI  - Readmission Following Radical Cystectomy: A Ray of Light in the "Black Box"?

PMID- 28753860
TI  - Metabolic Imaging of Prostate Cancer Reveals Intrapatient Intermetastasis
      Response Heterogeneity to Systemic Therapy.
AB  - : Although intrapatient heterogeneity of prostate cancer (PCa) has recently been
      characterized via genomic and transcriptomic studies, the heterogeneity of
      systemic treatment responses has yet to be reported or imaged. Our objective was
      to evaluate the intrapatient intermetastasis response to systemic treatment among
      patients with metastatic PCa. We evaluated the metabolic response for each
      individual metastatic lesion (n=165) in 15 patients with metastatic PCa who
      underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography
      before and at least 3 mo after initiation of a systemic therapy that did not
      change in that period. Intermetastasis heterogeneity was defined as opposite
      metabolic responses for at least two metastases from the same compartment (bone
      or soft tissue) between the two time points. We found intrapatient
      intermetastasis response heterogeneity in 40% of the cases in our retrospective
      series. Our results suggest that systemic therapies can induce heterogeneous
      responses among individual metastases in patients with PCa, supporting the
      polyclonal evolution of PCa in advanced disease. Molecular imaging may thus be
      useful in identifying clinical resistance early after therapy initiation and
      could also allow targeted biopsy of resistant clones for molecular analysis.
      PATIENT SUMMARY: Systemic therapies can lead to heterogeneous responses in
      individual metastases of prostate cancer in a patient. Molecular imaging may be
      useful for identifying heterogeneity and could allow targeted biopsy for
      molecular analysis or therapy.

PMID- 28753861
TI  - E2F1 Signalling is Predictive of Chemoresistance and Lymphogenic Metastasis in
      Penile Cancer: A Pilot Functional Study Reveals New Prognostic Biomarkers.
AB  - BACKGROUND: For penile cancer (PC) there are no known molecular predictors of
      lymphatic spread and/or chemoresistance. OBJECTIVE: To identify functional
      biomarkers that can predict malignant progression and treatment responsiveness.
      DESIGN, SETTING, AND PARTICIPANTS: We used four patient-derived PC cell lines and
      measured invasion and capillary tube formation, chemoresponsiveness, and mRNA and
      protein expression. Data were further validated in E2F1 transcription factor
      knockdown and overexpression experiments. We quantified E2F1 transcript levels in
      a set of nonmetastatic tumours (NM), metastasised primary tumours (PT), and lymph
      node metastases (M) from 24 patients. E2F1 immunohistochemistry was performed in
      another set of 13 PC biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Relationships between different parameters were analysed using Student t tests.
      Transcript levels in patient samples were compared using Mann-Whitney U tests.
      Significance was set at p<0.05. RESULTS AND LIMITATIONS: In cell lines
      established from lymph node metastases, E2F1 was more abundantly expressed, pRB
      was inactivated, and CDK2, CDK4, and cyclins D and E were elevated in comparison
      to cells from primary PC. Overexpression of E2F1 enhanced migratory capacity and
      lymphatic endothelial tubule formation, while depletion reduced invasiveness and
      increased chemosensitivity. VEGFR-3 and VEGF-C and mesenchymal markers were
      upregulated by high E2F1. E2F1 was clearly upregulated in infiltrative and
      metastatic primary tumours and metastases (NM vs PT, p<0.05; NM vs M, p<0.0005).
      E2F1 Quick scores increased from grade I to grade III tumours. A limitation of
      the study is the small number of patients. CONCLUSIONS: E2F1 is a driver of
      invasion and lymphatic dissemination and promotes chemoresistance. E2F1-related
      biomarkers might assist in stratifying PC patients for different treatment
      regimens. PATIENT SUMMARY: The availability of penile cancer cell lines allows
      molecular research on the mechanisms underlying metastasis and chemotherapy. A
      critical pathway involved in both features has been identified and may lead to
      better patient stratification for treatment selection.

PMID- 28753862
TI  - Validation of the Clavien-Dindo Grading System in Urology by the European
      Association of Urology Guidelines Ad Hoc Panel.
AB  - CONTEXT: Since 2012 uniformed reporting of complications after urological
      procedures has been advocated by the European Association of Urology (EAU)
      guidelines. The Clavien-Dindo grading system was recommended to report the
      outcomes of urologic procedures. OBJECTIVE: To validate the Clavien-Dindo grading
      system in urology. DESIGN, SETTING, AND PARTICIPANTS: Members of the EAU working
      group compiled a list of case scenarios including those with minor and major
      complications. A survey was administered online via Survey Monkey to the members
      of EAU committees for the appropriate grading according to the Clavien-Dindo
      classification of surgical complications. Scenarios with intraoperative
      complications were intentionally included to assess respondents' awareness of the
      Clavien-Dindo applicability. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Survey data collected were used to calculate agreement rates and to estimate the
      overall inter-rater agreement on all cases using Fleiss' kappa (kappa).
      Differences in agreement rates for each scenario among groups with different
      criteria about the system were estimated using the chi-square test. RESULTS AND
      LIMITATIONS: Evaluable responses were received from 81 out of 174 invited raters
      (46.5%). Of them 56.9% believed that the Clavien-Dindo system was adequate for
      grading postoperative complications. The agreement rate was over a score of >=80%
      in nine cases, 60-79% in 10 cases, 40-59% in 14 cases, and <40% in two cases.
      Interestingly, the agreement rate on the nonapplicability of the Clavien-Dindo
      system was quite low, ranging from 27.5% to 67.2% (kappa=0.147). Being a resident
      rather than a specialist affected only the distribution of agreement rates in
      case 1 (ie, score IIIb: 83.3% vs 94.1%). Being an academic or having affiliation
      did not have any impact on the distribution of agreement rates in all cases but
      one. CONCLUSIONS: The Clavien-Dindo classification is a standardised approach to
      grade and report postoperative complications in urology and should be used
      systematically. However, it does not apply for intraoperative complications, and
      there is a need for an additional tool. PATIENT SUMMARY: A rigorous methodology
      is mandatory when surgeons report about complications after surgery. In this
      study, the European Association of Urology Guidelines Panel has validated the use
      of the Clavien-Dindo grading system in urology.

PMID- 28753863
TI  - Exploratory Subgroup Analyses of Renal Function and Overall Survival in European
      Organization for Research and Treatment of Cancer randomized trial of Nephron
      sparing Surgery Versus Radical Nephrectomy.
AB  - BACKGROUND: In the European Organization for Research and Treatment of Cancer
      (EORTC) randomized trial 30904, nephron-sparing surgery (NSS) reduced the risk of
      renal dysfunction compared with radical nephrectomy (RN); however, overall
      survival was better in the RN arm. OBJECTIVE: To determine whether treatment
      effect on the risk of renal dysfunction and all-cause mortality differed in
      magnitude across levels of baseline variables. DESIGN, SETTING, AND PARTICIPANTS:
      This was an exploratory subgroup analysis of EORTC 30904, a phase 3 randomized
      trial conducted in patients with a small (<=5cm) renal mass and normal
      contralateral kidney. INTERVENTION: Patients were randomized to RN (n=273) or NSS
      (n=268). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: End points included
      follow-up estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2, eGFR
      <45ml/min/1.73m2, eGFR <30ml/min/1.73m2, and all-cause mortality. Treatment
      effect was examined within baseline variables: age (<62 vs >=62 yr), sex, chronic
      disease (any vs none), performance status (0 vs>=1), and serum creatinine <=1.25
      vs >1.25*upper limit of normal (ULN). Logistic and Cox regression models were
      used for analysis of renal dysfunction and all-cause mortality, respectively.
      RESULTS AND LIMITATIONS: The median follow-up periods were 6.7 yr for eGFR and
      9.3 yr for survival. No variable-by-treatment interactions were significant at
      alpha=0.05. For patients with baseline creatinine >1.25*ULN (n=36), estimated
      mortality hazard ratio (HR) for NSS versus RN reversed its direction (HR=0.76,
      95% confidence interval [CI]: 0.17-3.39) relative to the rest of the study cohort
      (HR=1.56, 95% CI: 1.06-2.29), although this reversal was not statistically
      significant (interaction p=0.25). This analysis was limited by low power.
      CONCLUSIONS: This exploratory analysis did not reveal strong evidence of
      treatment effect modification in EORTC 30904, but it was limited by low power.
      PATIENT SUMMARY: We aimed to determine whether the effect of partial versus
      radical nephrectomy on kidney function and overall survival depended on age, sex,
      and baseline health of patients enrolled in a large clinical trial. Such
      dependence could not be demonstrated in this analysis.

PMID- 28753864
TI  - Predicting Prostate Cancer Progression as a Function of ETS-related Gene Status,
      Race, and Obesity in a Longitudinal Patient Cohort.
AB  - BACKGROUND: ETS-related gene (ERG) oncogenic activation is the most common
      genomic alteration in prostate cancer (CaP) although it occurs less frequently in
      African American (AA) versus Caucasian (CA) patients, and the potential role of
      ERG as a prognostic marker has not been confirmed. OBJECTIVE: This study was
      conducted to confirm strong racial variation in the prevalence of ERG oncoprotein
      expression and to examine ERG oncoprotein expression, race, and body mass index
      as independent and joint predictors of CaP biochemical recurrence (BCR) following
      radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: A retrospective
      cohort study of CA and AA CaP patients enrolled at Walter Reed National Military
      Medical Center, who donated clinically annotated, whole-mounted, prostatectomy
      specimens between 1994 and 2014 following RP, was conducted. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: Kaplan-Meier (KM) estimation curves and multivariable
      Cox proportional hazards models were used to examine time to BCR as a function of
      ERG status, patient race, and obesity. RESULTS AND LIMITATIONS: Among 930
      eligible patients (36.1% AA and 63.9% CA), with 155 (16.7%) BCR events and a
      median follow-up time of 5.1 yr, ERG oncoprotein expression was significantly
      less prevalent in index tumors of AA versus CA patients (23.2% vs 49.3%;
      p<0.0001). KM curves showed significantly poorer BCR-free survival for CA
      patients with ERG-negative index tumors but not for AA patients. Race-stratified
      multivariable analyses revealed a significant association between ERG-negative
      index tumors and poorer BCR-free survival among CA patients (hazards ratio=1.67,
      confidence interval=1.07, 2.61; p=0.024). Less heterogeneity in ERG expression
      among AA patients may reduce the ability to show its association with BCR.
      CONCLUSIONS: Striking racial variation in ERG oncoprotein expression was
      confirmed. A novel observation was the importance of index tumor ERG-negative
      status in predicting CaP progression for CA patients. PATIENT SUMMARY: ETS
      related gene (ERG) typing of tumors may be useful in prognosticating prostate
      cancer aggressiveness.

PMID- 28753865
TI  - Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic
      Review.
AB  - CONTEXT: Prostate cancer stratification is based on tumour size, pretreatment PSA
      level, and Gleason score, but it remains imperfect. Current research focuses on
      the discovery and validation of novel prognostic biomarkers to improve the
      identification of patients at risk of aggressive cancer or of tumour relapse.
      OBJECTIVE: This systematic review by the Intergroupe Cooperateur Francophone de
      Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical
      validity and clinical validity and utility of six prognostic biomarkers (PHI,
      4Kscore, MiPS, GPS, Prolaris, Decipher). EVIDENCE ACQUISITION: All available data
      for the six biomarkers published between January 2002 and April 2015 were
      systematically searched and reviewed. The main endpoints were aggressive prostate
      cancer prediction, additional value compared to classical prognostic parameters,
      and clinical benefit for patients with localised prostate cancer. EVIDENCE
      SYNTHESIS: The preanalytical and analytical validations were heterogeneous for
      all tests and often not adequate for the molecular signatures. Each biomarker was
      studied for specific indications (candidates for a first or second biopsy, and
      potential candidates for active surveillance, radical prostatectomy, or adjuvant
      treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore
      were the biomarkers with the highest LOE for discriminating aggressive and
      indolent tumours in different indications. CONCLUSIONS: Blood biomarkers (PHI and
      4Kscore) have the highest LOE for the prediction of more aggressive prostate
      cancer and could help clinicians to manage patients with localised prostate
      cancer. The other biomarkers show a potential prognostic value; however, they
      should be evaluated in additional studies to confirm their clinical validity.
      PATIENT SUMMARY: We reviewed studies assessing the value of six prognostic
      biomarkers for prostate cancer. On the basis of the available evidence, some
      biomarkers could help in discriminating between aggressive and non-aggressive
      tumours with an additional value compared to the prognostic parameters currently
      used by clinicians.

PMID- 28753866
TI  - Diagnostic and Prognostic MicroRNA Biomarkers for Prostate Cancer in Cell-free
      Urine.
AB  - BACKGROUND: Widespread use of prostate-specific antigen (PSA) testing for
      prostate cancer (PC) detection has led to extensive overdiagnosis and
      overtreatment. Urine-based microRNA (miRNA) biomarkers could be useful in PC
      diagnosis and prognosis. OBJECTIVE: To train and validate urine-based microRNA
      (miRNA) biomarkers that may assist in PC diagnosis and prognosis. DESIGN,
      SETTING, AND PARTICIPANTS: We profiled the expression levels of 92 miRNAs via
      reverse transcriptase-poymerase chain reaction in cell-free urine samples from 29
      patients with benign prostatic hyperplasia (BPH) and 215 patients with clinically
      localized PC (cohort 1). Our findings were validated in an independent cohort of
      29 BPH patients and 220 patients with clinically localized PC (cohort 2). RESULTS
      AND LIMITATIONS: We identified and validated several deregulated miRNAs in urine
      samples from PC patients. In addition, we trained a novel diagnostic three-miRNA
      model (miR-222-3p*miR-24-3p/miR-30c-5p) that distinguished BPH and PC patients
      with an area under the curve (AUC) of 0.95 in cohort 1, and was successfully
      validated in cohort 2 (AUC 0.89). Furthermore, we trained a novel prognostic
      three-miRNA model (miR-125b-5p*let-7a-5p/miR-151-5p) that predicted time to
      biochemical recurrence after radical prostatectomy independently of routine
      clinicopathological parameters in cohort 1, and was successfully validated in
      cohort 2. CONCLUSIONS: Future clinical implementation of our novel diagnostic and
      prognostic three-miRNA signatures could help in primary diagnosis of PC and guide
      treatment decisions. Further validation studies are warranted. PATIENT SUMMARY:
      Using two large patient cohorts, we searched for novel prostate cancer biomarkers
      in urine. We found two new sets of microRNA biomarkers in urine that could
      accurately predict the presence of prostate cancer and the likelihood of
      recurrence after prostatectomy. Further studies are needed before an actual
      clinical test can be developed.

PMID- 28753867
TI  - Does the Unexpected Presence of Non-organ-confined Disease at Final Pathology
      Undermine Cancer Control in Patients with Clinical T1N0M0 Renal Cell Carcinoma
      Who Underwent Partial Nephrectomy?
AB  - BACKGROUND: A non-negligible proportion of individuals diagnosed with cT1 renal
      cell carcinoma (RCC) are upstaged to pT3a at final pathology. Few data on
      oncological outcomes for these patients are available to determine whether
      partial nephrectomy (PN) might jeopardise cancer control. OBJECTIVE: To assess,
      within an international multi-institutional collaboration, whether PN might
      undermine cancer control relative to radical nephrectomy (RN) in RCC patients
      with unexpected pT3a disease. DESIGN, SETTING, AND PARTICIPANTS: International
      multi-institutional collaboration including patients with cT1abN0M0-pT3a RCC.
      INTERVENTION: PN or RN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used
      Kaplan-Meier analyses, before and after propensity-score matching, to evaluate
      differences in metastatic progression (MP) and cancer-specific mortality (CSM)
      rates during follow-up. Univariable and multivariable Cox regression analyses
      were used to assess predictors of MP and CSM. RESULTS AND LIMITATIONS: Overall,
      309 patients with cT1abN0M0 RCC (cT1aN0M0, n=107, 34.6%; cT1bN0M0, n=202, 65.4%)
      had pT3a disease according to final pathology. Patients were treated with either
      PN (n=71, 23%) or RN (n=238, 77%). MP at 1, 2, and 5 yr was detected in 9.1%,
      13.3%, and 24.1% of patients, respectively. CSM was 3.5%, 10.7%, and 18.4% at 1,
      2, and 5 yr, respectively. After matching, no difference in terms of MP or CSM
      was observed between the PN and RN cohorts (both p>0.3). On multivariable
      analysis, type of surgery (PN vs RN) was not an independent predictor of either
      MP (p=0.3) or CSM (p=0.4). Limitations include the retrospective design.
      CONCLUSIONS: In patients with unexpected pT3a RCC at final pathology, PN does not
      appear to jeopardise cancer control with regard to MP and CSM. PATIENT SUMMARY:
      Cancer control is similar between patients treated with removal of the entire
      kidney and those with only partial removal, even if the final histology
      examination demonstrates a tumour that is unexpectedly not confined within the
      kidney.

PMID- 28753868
TI  - Outcomes of Early Endoscopic Realignment Versus Suprapubic Cystostomy and Delayed
      Urethroplasty for Pelvic Fracture-related Posterior Urethral Injuries: A
      Systematic Review.
AB  - CONTEXT: The evidence base for optimal acute management of pelvic fracture
      related posterior urethral injuries needs to be reviewed because of evolving
      endoscopic techniques. The current standard of care is suprapubic cystostomy
      followed by delayed urethroplasty. OBJECTIVE: To systematically review the
      evidence base comparing early endoscopic realignment with cystostomy and delayed
      urethroplasty regarding stricture rate, the need for subsequent procedures, and
      functional outcomes. EVIDENCE ACQUISITION: A systematic search in Medline,
      Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of
      Systematic Review, and www.clinicaltrials.gov without time or language
      limitations. Both medical subject heading and free text terms as well as
      variations of root word were searched. Randomised controlled trials (RCTs),
      nonrandomised comparative studies and single-arm case series were included, as
      long as >=10 patients were enrolled. Data were narratively synthesised in light
      of methodological and clinical heterogeneity. The risk of bias of each included
      study was assessed. EVIDENCE SYNTHESIS: No RCTs were found. Six nonrandomised
      comparative studies and met inclusion criteria and were selected for data
      extraction. Noncomparative studies with more than 10 participants were included
      resulting in seven eligible studies. From the comparative papers the results of
      219 patients were reported: 142 in the realignment group and 77 in the group
      undergoing cystostomy with delayed repair. The noncomparative studies reported on
      a further 150 cases. An overall stricture rate of 49% was evident in the
      endoscopic realignment group. Of these patients, 50% (28.1% overall) could be
      managed by endoscopic procedures and 40.3% (18.5% of intervention group) required
      anastomotic repair. CONCLUSIONS: No RCTs were found and the included
      nonrandomised studies have heterogeneous populations and a high degree of bias.
      About half of the patients were free of stricture and thus did not undergo
      delayed urethroplasty in case early endoscopic realignment had been performed.
      PATIENT SUMMARY: This systematic review of literature of urethral trauma revealed
      there are no well conducted comparative studies of newer endoscopic treatments
      versus standard treatments which include more extensive surgery. The results of
      the reports we selected based on specific characteristics are often influenced by
      variable factors. After careful analysis of these results we can conclude that
      the newer endoscopic techniques might resolve the risk of urethral injury due to
      pubic fractures in about half of the patients. Because of various confounders we
      cannot identify those patients who would benefit from this procedure or who might
      be possibly harmed.

PMID- 28753869
TI  - PTEN Loss but Not ERG Expression in Diagnostic Biopsies Is Associated with
      Increased Risk of Progression and Adverse Surgical Findings in Men with Prostate
      Cancer on Active Surveillance.
AB  - BACKGROUND: Active surveillance (AS) is an option for men with low-risk prostate
      cancer (PCa). PTEN and ERG have been considered as potential biomarkers of PCa
      progression and survival. OBJECTIVE: To study the role of ERG and PTEN status in
      the Prostate Cancer Research International: Active Surveillance (PRIAS) trial
      diagnostic biopsies (DBxs) in predicting surveillance discontinuation and adverse
      surgical findings in subsequent radical prostatectomy (RP). DESIGN, SETTING, AND
      PARTICIPANTS: A total of 231 patients were recruited to the PRIAS between 2007
      and 2013 in Helsinki. DBx tissue for immunohistochemistry (IHC) was available
      from 190 patients. Tissue microarrays (TMAs) were constructed from 57 specimens
      of subsequent RPs. DBxs containing grade group (GG) 1 PCa and RP TMA sections
      were stained with ERG and PTEN antibodies, and scored as either negative or
      positive. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Outcomes were followed
      up by biopsy GG upgrade (GG >= 2) and protocol-based treatment change, as well as
      adverse findings in RP (GG >= 3 or pathological stage>=3). Clinical variables and
      biomarker status in DBx were correlated in Cox regression analysis and cumulative
      survival in Kaplan-Meier analysis, and finally, Gray's competing risk analysis
      was performed and nonprotocol-based discontinuation was considered as a competing
      event. RESULTS AND LIMITATIONS: In both uni- and multivariate Cox regression
      analyses, only the number of positive cores in the DBx, the number of rebiopsy
      sessions, and PTEN status at diagnosis were significantly associated with
      rebiopsy GG upgrade, treatment change, and adverse histopathology in RP. In
      Kaplan-Meier analysis, PTEN loss was associated with a shorter time to GG upgrade
      and treatment change. Patients with PTEN loss had a higher probability for
      protocol-based discontinuation but not for competing risk factors compared with
      patients with intact PTEN. Biopsy ERG status was concordant with RP TMA ERG
      status, while PTEN was not. Limitations include a retrospective analysis of
      prospective cohort data. CONCLUSIONS: PTEN status at diagnosis is a potential
      biomarker for identifying patients with PCa on AS with a high risk for
      progression or adverse findings on subsequent RP. PATIENT SUMMARY: A simple
      diagnostic biopsy-based analysis of PTEN status may help identify patients with
      high risk for prostate cancer progression.

PMID- 28753870
TI  - Outcomes of Prostate-specific Antigen-based Prostate Cancer Screening Among Men
      Using Nonsteroidal Anti-inflammatory Drugs.
AB  - BACKGROUND: The Finnish Randomized Study of Screening for Prostate Cancer
      (FinRSPC), the largest component of the European Randomized Study of Screening
      for Prostate Cancer (ERSPC), showed a smaller, nonsignificant reduction in
      prostate cancer-specific mortality by systematic prostate-specific antigen (PSA)
      based screening compared with the overall ERSPC results. Nonsteroidal anti
      inflammatory drugs (NSAIDs) reduce inflammation and also PSA elevations due to
      intraprostatic inflammation. OBJECTIVE: To explore whether NSAID usage modifies
      the effects of PSA-based screening on prostate cancer incidence and mortality.
      DESIGN, SETTING, AND PARTICIPANTS: A cohort of 78 165 men from the FinRSPC were
      linked to a comprehensive national prescription database to obtain information on
      NSAID reimbursements prior to screening. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Prostate cancer risk and mortality were compared between the FinRSPC
      screening arm and the control arm among NSAID users and nonusers using an age
      adjusted Cox regression model. RESULTS AND LIMITATIONS: Screening increased the
      detection of Gleason 6 (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.47
      1.72 and HR 1.39, 95% CI 1.26-1.54) and localized prostate tumors (HR 1.25, 95%
      CI 1.18-1.32 and HR 1.11, 95% CI 1.03-1.20) more among baseline NSAID nonusers
      than among users, respectively (p for interaction <0.04 for both). This
      difference was observed in all three screening rounds. Detection of metastatic
      prostate cancer was similar in both NSAID users and nonusers. Screening decreased
      prostate cancer mortality among men using NSAIDs at FinRSPC randomization (HR
      0.66, 95% CI 0.49-0.90) but not among nonusers (HR 0.95, 95% CI 0.81-1.12); p for
      interaction=0.04. CONCLUSIONS: Screening detected fewer well-differentiated
      localized tumors among NSAID users than among nonusers. This suggests that PSA
      screening may cause less overdiagnosis within this subgroup, whereas mortality
      benefit may be greater among NSAID users. PATIENT SUMMARY: Prostate cancer
      screening causes less overdiagnosis of well-differentiated localized prostate
      tumors among men who use nonsteroidal anti-inflammatory drugs.

PMID- 28753871
TI  - European Association of Urology Section of Urolithiasis (EULIS) Consensus
      Statement on Simulation, Training, and Assessment in Urolithiasis.
AB  - BACKGROUND: Simulation-based training offers an acceptable adjunct to the
      traditional mentor-apprentice model in helping trainees to traverse the early
      stages of the learning curve for ureteroscopy and percutaneous renal surgery. In
      addition, nontechnical skills are increasingly important in preventing adverse
      events in the operating room, and simulation-based training can be used for
      training in such skills. Incorporation of simulation into formalised,
      standardised, and validated curricula offers an applicable method for training
      residents. OBJECTIVE: To develop a curriculum for urolithiasis procedures
      incorporating technical and nontechnical skills training for implementation
      across Europe. DESIGN, SETTING, AND PARTICIPANTS: An international panel of
      experts from EULIS, EUREP, ESU and ESUT was consulted in five stages. The study
      incorporated a mix of qualitative and quantitative data for collection and
      analysis. Responses were drawn out in (1) an opinion survey and (2) a curriculum
      development survey, which were discussed in (3) a focus group meeting. Group
      responses from this meeting were analysed for themes, which were discussed at (4)
      a focus group meeting, where consensus was reached among the group. Data analysis
      and integration at this stage were used to draft the curriculum. RESULTS AND
      LIMITATIONS: All group meetings were transcribed from the focus group discussion.
      Eight themes were generated, into which all data were categorised. These were:
      need for a training curriculum; curriculum objectives; curriculum structure;
      curriculum content; teaching platforms and tools; assessment and certification;
      validation and implementation; and global integration of the curriculum. A
      curriculum, including recommended simulators for use, was subsequently proposed.
      CONCLUSIONS: We propose a comprehensive curriculum for training in urolithiasis.
      Additional planning is required for full validation and implementation before it
      can be used to train residents. PATIENT SUMMARY: Stone disease accounts for a
      major proportion of surgical interventions worldwide. We describe a consensus
      guideline for effective training of stone surgeons.

PMID- 28753872
TI  - Small-cell Carcinomas of the Urinary Bladder and Prostate: TERT Promoter Mutation
      Status Differentiates Sites of Malignancy and Provides Evidence of Common
      Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial
      Carcinoma.
AB  - BACKGROUND: Small-cell carcinoma (SCC) of the urinary bladder frequently appears
      alongside urothelial carcinoma, suggesting common clonality. TERT promoter
      mutations have been recently implicated in urothelial carcinogenesis. OBJECTIVE:
      To investigate the degree to which TERT promoter mutations are involved in SCC of
      the urinary bladder, the linked tumorigenesis between urothelial carcinoma and
      SCC of the urinary bladder, and the molecular distinctions between SCC of the
      urinary bladder and of the prostate. DESIGN, SETTING, AND PARTICIPANTS: We
      investigated TERT promoter mutations in 53 cases of SCC of the urinary bladder
      and in 26 cases of SCC of the prostate using laboratory-based studies of tissue
      samples and clinical data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We
      measured the frequency of TERT promoter mutations in SCCs of the urinary bladder
      and prostate, and concordance of the mutation status between concurrent urinary
      bladder SCC and urothelial carcinoma. RESULTS AND LIMITATIONS: TERT promoter
      mutations were detected in 29/53 (55%) cases of urinary bladder and 0/26 (0%)
      cases of prostate SCC. Of 25 cases with concurrent urinary bladder SCC and non
      small-cell components, all cases harbored identical TERT promoter mutation status
      in both phenotypes. CONCLUSIONS: TERT promoter mutations are found in more than
      half of urinary bladder SCCs. Mutation status is also identical in urothelial
      carcinoma and SCC components of concomitant malignancies, providing evidence of a
      common clonality. TERT promoter mutation status can differentiate SCC of the
      urinary bladder from prostate SCC, suggesting potential diagnostic use. PATIENT
      SUMMARY: Small-cell carcinoma of the urinary bladder shares a common clonal
      origin with conventional urothelial carcinoma and may arise from a heterogeneous
      subclone. TERT promoter mutations may have utility as a differential biomarker
      for determining the primary site of a genitourinary small-cell carcinoma.

PMID- 28753873
TI  - Comment on "neurogenic bladder in a girl after surgery for cloacal malformation".
AB  - In children with a neurogenic bladder and bowel, all options for continent and
      incontinent diversions have to be discussed in detail including all advantages
      and disadvantages with the patient, parents, caregivers and all disciplines
      involved.

PMID- 28753874
TI  - Systematic Review of the Volume-Outcome Relationship for Radical Prostatectomy.
AB  - CONTEXT: Radical prostatectomy (RP) is one of the most complex urological
      procedures performed. Higher surgical volume has been found previously to be
      associated with better patient outcomes and reduced costs to the health care
      system. This has resulted in some regionalization of care toward high-volume
      facilities and providers; however, the preponderance of RPs is still performed at
      low-volume institutions. OBJECTIVE: To provide an updated systematic review of
      the association of hospital and surgeon volume on patient and system outcomes
      after RP, including robot-assisted RP. EVIDENCE ACQUISITION: A systematic review
      of literature was undertaken, searching PubMed (1959-2016) for original articles.
      Selection criteria included RP, hospital and/or surgeon volumes as predictor
      variables, categorization of hospital and/or surgeon volumes, and measurable end
      points. EVIDENCE SYNTHESIS: Overall 49 publications fulfilled the inclusion
      criteria. Most of the studies demonstrated that higher-volume surgeries are
      associated with better outcomes including reduced mortality, morbidity,
      postoperative complications, length of stay, readmission, and cost-associated
      factors. The volume-outcome relationship is maintained in robotic surgery. Eleven
      studies assessed hospital and surgeon volume simultaneously, and findings reflect
      that neither is an independent predictor variable affecting outcomes. The studies
      varied in how volume cutoffs were categorized as well as how the volume-outcome
      relationship was methodologically evaluated. CONCLUSIONS: Contemporary evidence
      continues to support the relationship between high-volume surgeries with improved
      RP outcomes. Recent studies demonstrate that the volume-outcome relationship
      applies to robot-assisted RP and may be applied for potential cost savings in
      health care. An increase in the number of international studies suggests
      reproducibility of the association. Although regionalization of surgical care
      remains a contentious issue, there is an increasing body of evidence that short
      term outcomes are improved at high-volume centers for RP. PATIENT SUMMARY: This
      systematic review of the latest literature found that higher surgical volume was
      associated with improved outcomes for radical prostatectomy.

PMID- 28753875
TI  - Islam and the Urinary Stoma: A Contemporary Theological and Urological Dilemma.
AB  - BACKGROUND: The prayer ritual is an essential component of Islam that requires
      entry into a state of physical purity (wudhu) through ablution, which is
      invalidated by voiding. An important dilemma for patients and surgeons may arise
      when a Muslim patient is counselled on cystectomy because of the belief by some
      that an incontinent urinary diversion will automatically invalidate their wudhu.
      OBJECTIVE: To determine if there are any religious barriers and implications for
      Muslim patients undergoing an incontinent urinary diversion. DESIGN, SETTING, AND
      PARTICIPANTS: A questionnaire was distributed to all UK mosques, addressed to the
      imam (n=804). RESULTS AND LIMITATIONS: A total of 134 imams (response rate 16.7%)
      responded. There was general agreement among imams, with >90% answering that it
      is possible for a Muslim to perform ablution, pray, and enter a mosque with a
      urinary stoma. The majority of imams (86.6%) also stated that refusal of a
      urinary stoma was not justified by religious teachings. When asked if patients
      should choose the option of a neobladder despite this surgery having greater
      risk, 57.5% of respondents stated that they were either unsure or agreed with
      this alternative. CONCLUSIONS: The majority of imams agreed that Muslims with a
      urinary stoma are able to maintain their ablution, allowing them to conduct their
      daily prayers, and that this form of surgery should not be refused on religious
      grounds. Our study suggests that the consensus view is that a urinary stoma is
      not contraindicated with regard to the practice of Islamic prayer rituals.
      PATIENT SUMMARY: In this study we investigated if having a urinary stoma would be
      a religious barrier for Muslim patients in performing their obligatory prayer
      rituals. The overwhelming majority of imams stated that having a urinary stoma
      should not stop Muslim patients practising important aspects of their faith.

PMID- 28753876
TI  - Emerging Utility of Urinary Cell-free Nucleic Acid Biomarkers for Prostate,
      Bladder, and Renal Cancers.
AB  - CONTEXT: By 2020 the estimated incidence of genitourinary (GU) cancers (prostate,
      bladder, and kidney) will be over 2 million worldwide and responsible for ~800
      000 deaths. Current diagnosis and monitoring methods of GU cancer patients are
      often invasive and/or lack sensitivity and specificity. Given the utility of
      blood-based cell-free nucleic acid (cfNA) biomarkers, the development of urinary
      cfNA biomarkers may improve the sensitivity of urine assays utilizing urine
      sediment for GU cancers. This review of urinary cfNA in GU cancers identifies the
      current stage of research, potential clinical utility, and the next steps needed
      to enter clinical use. OBJECTIVE: To critically evaluate the literature of
      urinary cfNA in GU cancers for clinical utility in diagnosis, screening, and
      precision medicine. Furthermore, the strategy for future efforts to discover
      potential new urinary cfNA biomarkers will be described. EVIDENCE ACQUISITION: A
      PubMed database (2006 to current) search was performed according to Preferred
      Reporting Items for Systemic Review and Meta-analysis using key Medical Subject
      Headings terms. Additional studies were obtained by cross-referencing from the
      literature. EVIDENCE SYNTHESIS: The collective research publications in urinary
      cfNA of GU cancers present a promising alternative liquid biopsy approach
      compared with blood biopsies and urine sediment, particularly for early-stage GU
      diseases. CONCLUSIONS: Urinary cfNA as a liquid biopsy holds potential for a more
      sensitive alternative to blood biopsies and urine sediment-based tests for
      clinical use in GU cancers. Not only does urinary cfNA offer advantages including
      the potential for more frequent testing, monitoring, and home use, but also has
      applications in early-stage GU cancers. PATIENT SUMMARY: In this review, we
      evaluated the current status of urinary cell-free nucleic acid in genitourinary
      cancers. We identified the potential advantages of urinary cell-free nucleic acid
      over blood and urine sediment and its clinical use in genitourinary cancer.

PMID- 28753877
TI  - Does Cytoreductive Prostatectomy Really Have an Impact on Prognosis in Prostate
      Cancer Patients with Low-volume Bone Metastasis? Results from a Prospective Case
      Control Study.
AB  - : The impact of cytoreductive radical prostatectomy (CRP) on oncological outcomes
      in patients with prostate cancer (PCa) and distant metastases has been
      demonstrated by retrospective data with their potential selection bias. Using
      prospective institutional data, we compared the outcomes between 43 PCa patients
      with low-volume bone metastases (1-3 lesions) undergoing CRP (median follow-up
      32.7 mo) and 40 patients receiving best systemic therapy (BST; median follow-up
      82.2 mo). The inclusion criteria for both cohorts were identical. So far, no
      significant difference in castration resistant-free survival (p=0.92) or overall
      survival (p=0.25) has been detected. Compared to recent reports, the outcomes for
      our control group are more favorable, indicating a potential selection bias in
      the previous retrospective studies. Therefore, the unclear oncological effect has
      to be weighed against the potential risks of CRP. However, patients benefit from
      a significant reduction in locoregional complications (7.0% vs 35%; p<0.01) when
      undergoing CRP. PATIENT SUMMARY: In this study we analyzed the impact of surgery
      in patients with prostate cancer and bone metastases. Using prospective data, we
      could not show a significant benefit of surgery on survival, but the rate of
      locoregional complications was lower. Therefore, patients should be treated
      within prospective trials evaluating the role of cytoreductive prostatectomy in
      low-volume, bone metastatic prostate cancer.

PMID- 28753878
TI  - Short-term Outcomes and Costs Following Partial Nephrectomy in England: A
      Population-based Study.
AB  - BACKGROUND: The benefits of minimally invasive partial nephrectomy (PN) for
      localised renal cancers are well established. Outcomes and hospital activity
      following PN have not been studied for the English National Health System,
      despite a growing use of robotic-assisted PN (RAPN). OBJECTIVE: To compare 90-d
      complication rates and 1-yr hospital activity and costs following PN using
      routinely-collected national data. DESIGN, SETTING, AND PARTICIPANTS: We analysed
      Hospital Episode Statistics data for 4275 patients undergoing open PN (OPN),
      laparoscopic PN, or RAPN between October 2008 and September 2014. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Hospital activity and costs estimated
      using multivariate Generalised Linear Models. Logistic regression was used to
      model postoperative complications. RESULTS AND LIMITATIONS: Compared with RAPN,
      OPN experienced more frequent 90-d readmissions for wound-related complications
      (n=68 vs n=3, p=0.014) and postoperative infections (n=151 vs n=11, p=0.045). One
      year inpatient admissions were higher in OPN (incidence rate: 1.628 vs 0.928,
      p=0.004). Outcomes in laparoscopic PN and RAPN were equivalent. In comparison to
      OPN, RAPN was associated with lower complication-related costs at 90 d (mean
      L317.21 vs L129.29, p=0.002) and total costs at 1 yr (mean L2998.55 vs L2089.37,
      p=0.024). Limitations were the absence of clinical indicators for risk
      adjustment. CONCLUSIONS: Hospital activity is significantly lower in the year
      immediately following RAPN compared with OPN. This is driven in part by a
      reduction in postoperative complications requiring readmission, reflecting lower
      total costs. PATIENT SUMMARY: We analysed national data for 4275 patients
      undergoing partial nephrectomy via open, laparoscopic, or robotic assisted
      laparoscopic surgery in England over a 6-yr period. Robotic assisted laparoscopic
      surgery was associated with fewer 90-d complications and lower total costs at 1
      yr postintervention.

PMID- 28753879
TI  - Robot-assisted Versus Open Radical Cystectomy in Patients Receiving Perioperative
      Chemotherapy for Muscle-invasive Bladder Cancer: The Oncologist's Perspective
      from a Multicentre Study.
AB  - BACKGROUND: Little is known about the outcomes of robot-assisted radical
      cystectomy (RARC) compared to open radical cystectomy (ORC) combined with
      perioperative chemotherapy for muscle-invasive urothelial bladder cancer (UBC).
      OBJECTIVE: To evaluate surgical and oncological outcomes for RARC and ORC in
      multimodal treatment. DESIGN, SETTING, AND PARTICIPANTS: Data from 28 centres
      were collected for cystectomies performed between January 2000 and July 2013.
      INTERVENTION: RARC or ORC combined with perioperative chemotherapy for UBC.
      OUTCOME MEASURES AND STATISTICAL ANALYSIS: Fisher's exact tests, chi2 tests, and
      Wilcoxon rank-sum tests were used to compare the RARC and ORC groups. Logistic
      and Cox regression analyses were performed to evaluate potential prognostic
      factors. RESULTS AND LIMITATIONS: A total of 688 patients (n=603 ORC and n=85
      RARC) were analysed; 60.6% received neoadjuvant chemotherapy, and 45.1% adjuvant
      chemotherapy. No significant differences in baseline characteristics were found
      between the groups. The median time from surgery to adjuvant chemotherapy was 1.9
      mo for both RARC and ORC groups. The median number of lymph nodes removed was 21
      (interquartile range [IQR] 14-35) for RARC and 13 (IQR 8-21) for ORC (p<0.001);
      the results were confirmed in subgroup analyses. Multivariable analyses revealed
      no difference in the rate of positive surgical margins (p=0.54 and p=0.78), rate
      of neobladder diversion (p=0.33 and p=0.51), relapse-free survival (p=0.31 and
      p=0.23), and overall survival (p=0.63 and p=0.69). The retrospective nature of
      the data is the major limitation. CONCLUSIONS: In this study, no differences in
      efficacy outcomes or ability to deliver adjuvant chemotherapy were observed
      between RARC and ORC. The increasing use of RARC is justifiable from an
      oncological viewpoint. PATIENT SUMMARY: In a retrospective study of patients who
      received perioperative chemotherapy for urothelial bladder cancer, we found no
      difference in key outcomes between robot-assisted radical cystectomy (RARC) and
      open radical cystectomy. Performing RARC seems to be justifiable in the
      multidisciplinary setting.

PMID- 28753880
TI  - Paediatric Urology and the Dilemma of Low-quality Evidence for the Management of
      Common Urological Conditions (Vesicoureteral Reflux, Lower Urinary Tract
      Dysfunction, Undescended Testis) in Children.
AB  - We have to strive for a more prospective scientific approach to every specific
      urological condition in children, with contributions from all parties involved
      and an emphasis on proper outcome research.

PMID- 28753881
TI  - Platinum-based Neoadjuvant Chemotherapy Improves Oncological Outcomes in Patients
      with Locally Advanced Upper Tract Urothelial Carcinoma.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) use for patients with locally advanced
      upper tract urothelial carcinoma (UTUC) is debatable. OBJECTIVE: To investigate
      the efficacy and safety of platinum-based NAC for locally advanced UTUC. DESIGN,
      SETTINGS, AND PARTICIPANTS: Of 233 consecutive patients who underwent radical
      nephroureterectomy, 55 patients received NAC (NAC group) and 138 patients did not
      (Ctrl group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The two arms (Ctrl
      vs NAC) were matched using propensity scores to minimize selection bias. We
      retrospectively evaluated tumor response, post-therapy pathological downstaging,
      lymphovascular invasion, Ki67 status, and prognosis between pair-matched
      patients. Multivariate Cox regression analysis was performed for independent
      factors for prognosis. RESULTS AND LIMITATIONS: We selected 51 pair-matched
      patients in each group. The regimens in the NAC group included gemcitabine and
      carboplatin, and gemcitabine and cisplatin. The median response rate in the NAC
      group was 28%. NAC-related adverse events were tolerable. Pathological
      downstaging of the primary tumor was significantly higher in the NAC group than
      in the Ctrl group. The MIB1 index (immunostaining for Ki67) was significantly
      higher in the NAC group. NAC for locally advanced UTUC significantly prolonged
      progression-free, cancer-specific, and overall survival. Multivariate Cox
      regression analysis using an inverse probability of treatment weighting method
      showed that NAC was selected as an independent predictor for prolonged cancer
      specific survival. Limitations are the retrospective design and the small sample
      size. CONCLUSIONS: Platinum-based NAC for advanced UTUC potentially improves
      oncological outcomes. Further prospective studies are needed. PATIENT SUMMARY:
      Platinum-based neoadjuvant chemotherapy for locally advanced upper tract
      urothelial carcinoma was safe and potentially improves oncological outcomes. A
      carboplatin-based regimen may be used as an alternative in patients with impaired
      renal function.

PMID- 28753882
TI  - Statin Use and Survival in Patients with Metastatic Castration-resistant Prostate
      Cancer Treated with Abiraterone Acetate.
AB  - BACKGROUND: Although statin use has been associated with favorable effects in
      various solid malignancies, no conclusive evidence is available at present.
      Statins are safe and inexpensive, and may synergize with novel antiandrogen
      agents abiraterone via pharmacokinetic interactions and decrease substrate
      availability for de novo androgen biosynthesis. OBJECTIVE: To determine whether
      statin use affects survival in patients with metastatic castration-resistant
      prostate cancer (mCRPC) treated with abiraterone. DESIGN, SETTING, AND
      PARTICIPANTS: Medical records of patients with documented mCRPC between September
      2011 and August 2016 were reviewed at multiple participating centers. This
      research was conducted in ten institutions, including both referral centers and
      local hospitals. A total of 187 patients receiving abiraterone for mCRPC between
      September 2011 and August 2016 were eligible for inclusion in this retrospective
      study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were assessed for
      overall survival (OS), statin use at the time of treatment initiation, prostate
      specific antigen (PSA) variations, and other variables of interest. Univariable
      and multivariable analysis was used to explore the association of variables of
      interest with OS and PSA declines. RESULTS AND LIMITATIONS: Statin use was a
      significant prognostic factor for longer OS in univariable (hazard ratio [HR]
      0.51, 95% confidence interval [CI] 0.37-0.72; p<0.001) and multivariable analysis
      (HR 0.40, 95% CI 0.27-0.59; p<0.001) and was significantly associated with PSA
      declines (>50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users;
      p<0.001). CONCLUSIONS: Our study suggests a prognostic impact of statin use in
      patients receiving abiraterone for mCRPC. The mechanism of this interaction
      warrants elucidation, but may include enhancement of the antitumor activity of
      abiraterone as well as cardioprotective effects. PATIENT SUMMARY: We assessed the
      effects of statin use in patients with advanced prostate cancer receiving
      abiraterone. Patients treated with a statin plus abiraterone appeared to live
      longer than those treated with abiraterone only. Since no negative drug-drug
      interaction is known and statins are widely used and inexpensive, further studies
      assessing the use of abiraterone plus statins are warranted.

PMID- 28753883
TI  - Management of Radiologically Indeterminate Magnetic Resonance Imaging Signals in
      Men at Risk of Prostate Cancer.
AB  - BACKGROUND: Multiparametric magnetic resonance imaging (mp-MRI) is becoming an
      increasingly important diagnostic tool for prostate cancer. So far there has been
      little focus on management for indeterminate mp-MRI results. OBJECTIVE: To
      describe outcomes for a cohort of men rated as having an indeterminate mp-MRI
      result. DESIGN, SETTING, AND PARTICIPANTS: Patients were identified
      retrospectively from a single UK centre between October 2010 and January 2015.
      Patients were included if they had a Likert score of 3/5 on a first MRI scan
      without any prior prostate biopsy. Patients were offered one of two initial
      management strategies. Strategy 1 was an immediate targeted biopsy of the MRI
      lesion. Strategy 2 was a surveillance process comprising prostate-specific
      antigen monitoring and/or mp-MRI at intervals of 6-12 mo, with biopsy on a for
      cause basis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer detection and
      treatment outcomes were compared for the two strategies. RESULTS AND LIMITATIONS:
      Of 168 patients, 73 (43%) chose strategy 1 and 95 (57%) chose strategy two. The
      overall proportion of men with clinically significant cancer detected was 14%
      (23/168). The risk profile for cancer identified in the initial surveillance
      group was similar to that identified in the immediate biopsy group. Limitations
      of the study include the short follow-up. CONCLUSIONS: Men with indeterminate mp
      MRI were willing to forego immediate biopsy for a strategy of surveillance
      involving PSA measurement and/or mp-MRI repeated at intervals. The risk profile
      of the cancers identified by both strategies appeared similar, but many men in
      the surveillance group avoided the risks, complications, and costs of biopsy.
      Long-term results are awaited. PATIENT SUMMARY: This report compares two
      approaches for an uncertain magnetic resonance imaging result for clinically
      important prostate cancer: immediate biopsy versus surveillance with delayed
      biopsy if required. Delayed biopsy did not result in identification of cancer
      with adverse features, and many men benefited from avoiding a biopsy and its
      complications.

PMID- 28753884
TI  - A Classification System for Urodynamic Evaluation of Lower Urinary Tract System
      Dysfunction.
AB  - CONTEXT: A classification system for lower urinary tract system (LUTS)
      dysfunction, based on urodynamics, could support the evaluation and management of
      this pathological condition. OBJECTIVE: A new alphanumerical classification
      system is proposed for staging neurogenic and non-neurogenic LUTS dysfunction,
      according to the urodynamic evaluation. EVIDENCE ACQUISITION: This is a proposal
      based on experience from everyday clinical practice and represents an opinion
      open to discussion. EVIDENCE SYNTHESIS: The purpose of this alphanumerical
      classification is the establishment of a simple, unified staging system
      describing all LUTS dysfunction situations, after a urodynamic evaluation, in a
      way that can help in diagnosis, treatment, health professionals' communication,
      education, and research. CONCLUSIONS: This alphanumerical classification for LUTS
      dysfunction could become a unified standard and a prerequisite for ensuring the
      quality of care in all resource settings. Moreover, it would be useful for the
      future to include a classification as part of LUTS dysfunction registration.
      PATIENT SUMMARY: A new alphanumerical classification system is presented. The
      purpose of this classification is the establishment of a simple, unified staging
      system describing entire lower urinary tract system dysfunction situations in a
      way that could help in diagnosis, treatment, health professionals' communication,
      education, and research.

PMID- 28753885
TI  - Gastrointestinal Complications Following Radical Cystectomy Using Enhanced
      Recovery Protocol.
AB  - BACKGROUND: The development of enhanced recovery after surgery (ERAS) protocols
      for patients undergoing radical cystectomy (RC) represents a significant advance
      in perioperative care. OBJECTIVE: To evaluate gastrointestinal (GI) complications
      following RC and urinary diversion (UD) using our institutional ERAS protocol.
      DESIGN, SETTING, AND PARTICIPANTS: We identified 377 consecutive cases of open RC
      and UD for which our ERAS protocol was used from May 2012 to December 2015.
      Exclusion criteria were consent refusal; non-bladder primary disease; palliative,
      salvage, or additional surgery; and prolonged postoperative intubation. A matched
      cohort of 144 patients for whom a traditional postoperative protocol (pre-ERAS)
      was used between 2003 and 2012 was selected for comparison. RESULTS AND
      LIMITATIONS: A total of 292 ERAS patients with median age of 70 yr were included
      in the study, 65% of whom received an orthotopic neobladder. The median time to
      first flatus and bowel movement was 2 d. The median length of stay was 4 d. GI
      complications occurred in 45 patients (15.4%) during the first 30 d following RC,
      93% of which were of minor grade. The most common GI complication was
      postoperative ileus (POI) in 34 cases (11.6%). Some 22 patients (7.5%) required a
      nasogastric tube, and parenteral nutrition was required in three patients. The
      rate of 30-d GI complications was significantly lower in the ERAS cohort than in
      the control group (13% vs 27%; p=0.003), as was the rate of POI (7% vs 23%;
      p<0.001). This effect was independent of other variables (hazard ratio 0.38, 95%
      confidence interval 0.18-0.82; p=0.01). CONCLUSIONS: Our institutional ERAS
      protocol for RC is associated with significantly improved perioperative GI
      recovery and lower rates of GI complications. This protocol can be tested in
      multi-institutional studies to reduce GI morbidity associated with RC. PATIENT
      SUMMARY: In this study, we showed that an enhanced recovery protocol for patients
      undergoing radical cystectomy for bladder cancer was associated with a
      significantly shorter length of hospital stay and lower rates of gastrointestinal
      complications, especially postoperative ileus.

PMID- 28753886
TI  - Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial
      Cancer of the Bladder.
AB  - BACKGROUND: The first global lipidomic profiles associated with urothelial cancer
      of the bladder (UCB) and its clinical stages associated with progression were
      identified. OBJECTIVE: To identify lipidomic signatures associated with survival
      and different clinical stages of UCB. DESIGN, SETTING, AND PARTICIPANTS:
      Pathologically confirmed 165 bladder-derived tissues (126 UCB, 39 benign adjacent
      or normal bladder tissues). UCB tissues included Ta (n=16), T1 (n=30), T2 (n=43),
      T3 (n=27), and T4 (n=9); lymphovascular invasion (LVI) positive (n=52) and
      negative (n=69); and lymph node status N0 (n=28), N1 (n=11), N2 (n=9), N3 (n=3),
      and Nx (n=75). RESULTS AND LIMITATIONS: UCB tissues have higher levels of
      phospholipids and fatty acids, and reduced levels of triglycerides compared with
      benign tissues. A total of 59 genes associated with altered lipids in UCB
      strongly correlate with patient survival in an UCB public dataset. Within UCB,
      there was a progressive decrease in the levels of phosphatidylserine (PS),
      phosphatidylethanolamines (PEs), and phosphocholines, whereas an increase in the
      levels of diacylglycerols (DGs) with tumor stage. Transcript and protein
      expression of phosphatidylserine synthase 1, which converts DGs to PSs, decreased
      progressively with tumor stage. Levels of DGs and lyso-PEs were significantly
      elevated in tumors with LVI and lymph node involvement, respectively. Lack of
      carcinoma in situ and treatment information is the limitation of our study.
      CONCLUSIONS: To date, this is the first study describing the global lipidomic
      profiles associated with UCB and identifies lipids associated with tumor stages,
      LVI, and lymph node status. Our data suggest that triglycerides serve as the
      primary energy source in UCB, while phospholipid alterations could affect
      membrane structure and/or signaling associated with tumor progression. PATIENT
      SUMMARY: Lipidomic alterations identified in this study set the stage for
      characterization of pathways associated with these altered lipids that, in turn,
      could inform the development of first-of-its-kind lipid-based noninvasive
      biomarkers and novel therapeutic targets for aggressive urothelial cancer of the
      bladder.

PMID- 28753887
TI  - Minimally Invasive Surgical Ureterolithotomy Versus Ureteroscopic Lithotripsy for
      Large Ureteric Stones: A Systematic Review and Meta-analysis of the Literature.
AB  - CONTEXT: The management of large ureteric stones represents a technical and
      clinical challenge. OBJECTIVE: To investigate the safety and efficacy of
      minimally invasive surgical ureterolithotomy (MISU) in comparison with
      ureteroscopic lithotripsy (URS) for the treatment of large ureteric stones.
      EVIDENCE ACQUISITION: The Preferred Reporting Items for Systematic Review and
      Meta-analyses (PRISMA) guidelines were followed for the conduction of the study,
      which was registered in the PROSPERO database. Search string was "(laparoscop* OR
      retroperito* OR robot*) AND ureterolitho*"; database scope included PubMed,
      SCOPUS, Cochrane, and EMBASE. Primary end points were the stone-free (SFR) and
      complications rates. Secondary end points included operative time and hospital
      stay. Subgroup analyses were performed for stones 1-2 and >2cm, as well as
      different lithotripters and ureteroscopes. Meta-analysis and forest-plot diagrams
      were performed with the RevMan 5.3.5 software. EVIDENCE SYNTHESIS: After
      screening 673 publications, seven randomized controlled trials were eligible to
      be included in the meta-analysis. A total of 778 patients were pooled after the
      elimination of the dropouts. No robotic cohorts were found. Only upper ureteral
      stones were treated in the included studies. The SFR at discharge and 3 mo was
      higher with MISU with odds ratios of 6.30 (95% confidence interval [CI]: 3.05,
      13.01; I2=0%) and 5.34 (95% CI: 2.41, 8.81; I2=0%), respectively. The most common
      complications for MISU and URS were conversion to open surgery and stone
      migration to the renal pelvis, respectively. Favorable results in terms of
      operative time were observed in the case of URS with a mean difference of 29.5min
      (95% CI: 14.74, 44.26; I2=98%). Hospitalization time was favorable in the case of
      URS with a mean difference of 2.08 days (95% CI: 0.96, 3.20; I2=99%).
      CONCLUSIONS: This meta-analysis showed a significantly higher SFR at discharge
      and 3 mo for MISU in comparison with URS when upper ureteral stones were treated.
      Operative and hospitalization time favored URS over MISU. PATIENT SUMMARY: The
      current study investigated the literature on the minimally invasive management of
      large ureteric stones. The available evidence shows that both ureteroscopic
      lithotripsy and minimally invasive surgical ureterolithotomy could be considered
      for the treatment of these stones with similar results. The selection of the
      approach should be based on the advantages and disadvantages of each technique.

PMID- 28753888
TI  - Intraoperative Imaging Techniques to Support Complete Tumor Resection in Partial
      Nephrectomy.
AB  - CONTEXT: With more complex kidney tumors treated by nephron-sparing surgery
      (NSS), complete tumor resection is becoming increasingly challenging.
      Intraoperative imaging may improve the establishment of negative surgical
      margins. OBJECTIVE: To discuss intraoperative imaging techniques that may help
      achieve complete tumor resection in NSS of renal tumors. EVIDENCE ACQUISITION:
      PubMed was searched for English articles on intraoperative imaging during NSS of
      renal cell carcinoma published after 2005, and a reference search of retrieved
      articles was performed. EVIDENCE SYNTHESIS: Included studies reported about
      ultrasonography, fluorescence imaging, augmented reality, optical coherence
      tomography, and ex vivo magnetic resonance imaging (MRI). The number of patients
      included in these studies is limited, and randomized controlled trials have not
      been performed. Ultrasonography is a well-established technique to assess tumor
      localization and may be used to evaluate surgical margins of the resected
      specimen. Fluorescence imaging with indocyanine green may help differentiate
      tumor from normal kidney tissue. It is yet unclear whether fluorescence imaging
      can detect positive surgical margins. Augmented reality is best studied in
      robotic laparoscopic surgery, and may be useful for tumor localization and
      resection, if the problem of tissue deformation during surgery can be solved.
      More results have to be awaited about optical coherence tomography and ex vivo
      MRI. CONCLUSIONS: Ultrasonography is a widely used technique to assist the
      surgeon in partial nephrectomy nowadays, while the use of fluorescence imaging
      and augmented reality is emerging. Although various techniques can be used during
      NSS, the added value of intraoperative imaging to support negative surgical
      margins remains to be demonstrated. PATIENT SUMMARY: In this review, we discuss
      the value of various intraoperative imaging techniques that may help a urologist
      achieve complete tumor resection in nephron-sparing surgery for kidney tumors.
      Ultrasonography, fluorescence imaging, and augmented reality have been studied
      best, but their added value needs further investigation.

PMID- 28753889
TI  - The Association of Uromodulin Genotype with Renal Cancer Aggressiveness.
AB  - : The aim of the study was to investigate the association of the uromodulin
      (UMOD) genotype with patient health status and with renal cell carcinoma (RCC)
      aggressiveness. The UMOD genotype at the top single nucleotide variant rs4293393
      was determined in a cohort of 211 patients diagnosed with a renal mass and
      treated with surgery. Clinical data were prospectively collected. Due to the
      higher frequency of allele T relative to the lower frequency of allele C,
      recessive homozygous (CC), and heterozygous (TC) patients were grouped together
      and compared with homozygous (TT) patients. Mann-Whitney and chi-square tests
      were used to compare clinical characteristics after stratification for the UMOD
      genotype. UMOD genotype frequencies resulted TT and TC-CC in 67% (n=141) and 33%
      (n=70) of the population, respectively. The rate of cM1 RCC at clinical staging
      was higher in patients with genotype TT relative to patients with genotype TC-CC
      (18% vs 1%, p=0.001). Similarly, the rate of pT3-pT4 (41% vs 25%, p=0.047) and
      lymphovascular invasion (29% vs 13%, p=0.02) RCC at final pathology were higher
      in patients with genotype TT relative to patients with genotype TC-CC. PATIENT
      SUMMARY: In patients diagnosed with renal cell carcinoma and treated with
      surgery, uromodulin homozygous genotype is associated with more aggressive renal
      cell carcinoma clinical and pathological characteristics.

PMID- 28753890
TI  - Is Nonoperative Management the Best First-line Option for High-grade Renal
      trauma? A Systematic Review.
AB  - CONTEXT: The management of high-grade (Grade IV-V) renal injuries remains
      controversial. There has been an increase in the use of (NOM) but limited data
      exists comparing outcomes with open surgical exploration. OBJECTIVE: To conduct a
      systematic review to determine if NOM is the best first-line option for high
      grade renal trauma in terms of safety and effectiveness. EVIDENCE ACQUISITION:
      Medline, Embase, and Cochrane Library were searched for all relevant
      publications, without time or language limitations. The primary harm outcome was
      overall mortality and the primary benefit outcome was renal preservation rate.
      Secondary outcomes included length of hospital stay and complication rate. Single
      arm studies were included as there were few comparative studies. Only studies
      with more than 50 patients were included. Data were narratively synthesised in
      light of methodological and clinical heterogeneity. The risk of bias of each
      included study was assessed. EVIDENCE SYNTHESIS: Seven nonrandomised comparative
      and four single-arm studies were selected for data extraction. Seven hundred and
      eighty-seven patients were included from the comparative studies with 535
      patients in the NOM group and 252 in the open surgical exploration group. A
      further 825 patients were included from single-arm studies. Results from
      comparative studies: overall mortality: NOM (0-3%), open surgical exploration (0
      29%); renal preservation rate: NOM (84-100%), open surgical exploration (0-82%);
      complication rate: NOM (5-32%), open surgical exploration (10-76%). Overall
      mortality and renal preservation rate were significantly better in the NOM group
      whereas there was no statistical difference with regard to complication rate.
      Length of hospital stay was found be significantly reduced in the NOM group.
      Patients in the open surgical exploration group were more likely to have Grade V
      injuries, have a lower systolic blood pressure, and higher injury severity score
      on admission. CONCLUSIONS: No randomised controlled trials were identified and
      significant heterogeneity existed with regard to outcome reporting. However, NOM
      appeared to be safe and effective in a stable patient with a higher renal
      preservation rate, a shorter length of stay, and a comparable complication rate
      to open surgical exploration. Overall mortality was higher in the open surgical
      exploration group, though this was likely due to selection bias. PATIENT SUMMARY:
      The data of this systematic review suggest nonoperative management continues to
      be favoured to surgical exploration in the management of high-grade renal trauma
      whenever possible. However, comparisons between both interventions are difficult
      as patients who have surgery are often more seriously injured than those managed
      nonoperatively, and existing studies do not report on outcomes consistently.

PMID- 28753891
TI  - Evaluation of Prostate HistoScanning as a Method for Targeted Biopsy in Routine
      Practice.
AB  - BACKGROUND: Prostate HistoScanning (PHS) is a tissue characterization system used
      to enhance prostate cancer (PCa) detection via transrectal ultrasound imaging.
      OBJECTIVE: To assess the impact of supplementing systematic transrectal biopsy
      with up to three PHS true targeting (TT) guided biopsies on the PCa detection
      rate and preclinical patient assessment. DESIGN, SETTING, AND PARTICIPANTS: This
      was a prospective study involving a cohort of 611 consecutive patients referred
      for transrectal prostate biopsy following suspicion of PCa. PHS-TT guided cores
      were obtained from up to three PHS lesions of >=0.5cm3 per prostate and only one
      core per single PHS lesion. Histological outcomes from a systematic extended 12
      core biopsy (Bx) scheme and additional PHS-TT guided cores were compared. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Comparison of PHS results and
      histopathology was performed per sextant. The chi2 and Mann-Whitney test were
      used to assess differences. Statistical significance was set at p<0.05. RESULTS
      AND LIMITATIONS: PHS showed lesions of >=0.5cm3 in 312 out of the 611 patients
      recruited. In this group, Bx detected PCa in 59% (185/312) and PHS-TT in 87%
      (270/312; p<0.001). The detection rate was 25% (944/3744 cores) for Bx and 68%
      (387/573 cores) for PHS-TT (p<0.001). Preclinical assessment was significantly
      better when using PHS-TT: Bx found 18.6% (58/312) and 8.3% (26/312), while PHS-TT
      found 42.3% (132/312) and 20.8% (65/312) of Gleason 7 and 8 cases, respectively
      (p<0.001). PHS-TT attributed Gleason score 6 to fewer patients (23.4%, 73/312)
      than Bx did (32.4%, 101/312; p=0.0021). CONCLUSIONS: Patients with a suspicion of
      PCa may benefit from addition of a few PHS-TT cores to the standard Bx workflow.
      PATIENT SUMMARY: Targeted biopsies of the prostate are proving to be equivalent
      to or better than standard systematic random sampling in many studies. Our study
      results support supplementing the standard schematic transrectal ultrasound
      guided biopsy with a few guided cores harvested using the ultrasound-based
      prostate HistoScanning true targeting approach in cases for which multiparametric
      magnetic resonance imaging is not available.

PMID- 28753892
TI  - Primary Treatment for Prostate Cancer in an Elderly Man.
AB  - Since the patient wanted both his lower urinary tract symptoms and his prostate
      cancer to be treated together, he decided to undergo robot-assisted radical
      prostatectomy.

PMID- 28753893
TI  - Contemporary Trends in the Incidence of Metastatic Prostate Cancer Among US Men:
      Results from Nationwide Analyses.
AB  - : Studies have noted contrasting findings with regard to the contemporary
      incidence of metastatic prostate cancer (PCa) in the USA, especially in light of
      the United States Preventive Services Task Force (USPSTF) recommendations against
      prostate-specific antigen (PSA) screening in recent years. We used data from the
      18 population- based tumor registries of the Surveillance, Epidemiology and End
      Results (SEER) 2004-2013 database to study trends in the incidence of metastatic
      PCa among men stratified by age and race. Joinpoint regression analyses were
      performed to identify time points associated with any statistically significant
      change in incidence. Overall, there was a significant increase in incidence
      between 2009 and 2013 (annual percentage change [APC] 3.10%; p<0.05). In age
      stratified analyses, there was a continuous increase in the incidence of
      metastatic PCa from 2004 to 2013 among men aged 45-54 yr and 55-64 yr (APC 1.77%
      and 1.43% respectively; both p<0.05). For men aged >=75 yr there was a
      significant decline in the incidence of metastatic PCa from 2004 to 2011 (APC 
      2.07%; p<0.05) and a nonsignificant increase from 2011 onwards (APC 6.09%).
      Distinct incidence trends were noted for white and black men. While it is too
      early to presume that the recent decline in PSA screening secondary to the USPSTF
      statement is causally associated with our findings, our results highlight a
      concerning trend of increasing metastatic disease. Our results thus warrant
      validation in future longer-term studies on the contemporary incidence and
      mortality of metastatic PCa. PATIENT SUMMARY: We noted increasing incidence of
      metastatic prostate cancer from 2009 onwards among US men (especially those aged
      45-74 yr) in a population-based tumor registry. Pending validation in longer-term
      studies, our results suggest the need for close surveillance of trends for
      metastatic prostate cancer incidence and mortality.

PMID- 28753894
TI  - Validation of the Preoperative Score to Predict Postoperative Mortality in
      Patients Undergoing Radical Cystectomy.
AB  - : Standardized prediction of perioperative mortality risk is of major clinical
      concern in the radical cystectomy setting. We validated the recently developed
      Preoperative Score to Predict Postoperative Mortality (POSPOM) in a sample of
      1083 consecutive cystectomy patients treated between 1993 and 2014. POSPOM was
      calculated as originally described based on age and 13 further parameters; three
      parameters which were not available in our database were ignored. Thirty-day and
      90-d mortality were 1.0% and 4.1%, respectively. The areas under the receiver
      operator characteristic curves were 0.86 for 30-d mortality and 0.78 for 90-d
      mortality. Below the median of 27 POSPOM risk points, 30-d mortality was 0% and
      90-d mortality was 0.5%. Above this level, the corresponding figures were 1.7%
      and 6.5%, respectively. The 30-d (p<0.0001) and even the 90-d mortality rates
      (p=0.004) were lower than the POSPOM-predicted in-hospital mortality rate for
      this sample (5.8%). Nevertheless, with its good discriminative accuracy, POSPOM
      might standardize the prediction of postoperative mortality after radical
      cystectomy. The absolute mortality figures in a high volume academic center were,
      however, lower than predicted based on nationwide collected data. PATIENT
      SUMMARY: With a good discriminative accuracy, Preoperative Score to Predict
      Postoperative Mortality might standardize the prediction of postoperative
      mortality after radical cystectomy. The absolute mortality figures in a high
      volume academic center were, however, lower than predicted based on nationwide
      collected data.

PMID- 28753895
TI  - Oestradiol-releasing Biodegradable Mesh Stimulates Collagen Production and
      Angiogenesis: An Approach to Improving Biomaterial Integration in Pelvic Floor
      Repair.
AB  - BACKGROUND: Polypropylene meshes cause severe complications in some patients.
      Materials that are biomechanically compatible and can better integrate into host
      tissues are urgently needed. OBJECTIVE: To design an oestradiol-releasing
      electrospun poly-l-lactic acid (PLA) mesh and evaluate its ability to stimulate
      new extracellular matrix and new blood vessel formation. DESIGN, SETTING, AND
      PARTICIPANTS: Human adipose derived mesenchymal cells (ADMSC) were isolated from
      fat. PLA meshes with micro- to nano-sized fibres containing 1%, 5%, and 10%
      oestradiol were constructed and used for in vitro and in vivo experiments.
      INTERVENTION: The angiogenic potential of the fibrous meshes was evaluated using
      an in vivo chorioallantoic membrane and an in vitro chick aortic arch assays.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Oestradiol release was measured
      fluorometrically. The effect of fibrous meshes on proliferation and extracellular
      matrix (ECM) production of ADMSC was assessed using immunohistology. Mechanical
      properties were tested using a tensiometer. RESULTS AND LIMITATIONS: The
      ultrastructure of the mesh was not affected by the inclusion of oestradiol and
      mechanical properties were only slightly modified. Oestradiol was released from
      PLA meshes over a 5-mo period. ADMSCs cultured on oestradiol-releasing PLA meshes
      produced more ECM involving collagen I, collagen III, and elastin. Oestradiol
      releasing meshes doubled new blood vessel formation in the chorioallantoic
      membrane assay (p=0.001) and outgrowth of pro-angiogenic cells in the aortic arch
      assay (p=0.001). Further studies in longer-term animal models are required to
      confirm these results. CONCLUSIONS: Oestradiol-releasing PLA meshes increase ECM
      production and stimulate angiogenesis. As such, they are promising candidate
      materials to be used in pelvic floor repair and to improve the initial healing
      phase of a repair material following implantation. PATIENT SUMMARY: In this
      study, we designed a tissue engineered material to be used to support weakened
      pelvic floor tissues in women to avoid the complications associated with current
      surgical mesh. Our results showed that this material can stimulate new blood
      vessel formation in simple chick assays and tissue production in vitro. Both
      properties should help with the integration of this material into patients'
      tissues and merit further study in physiologically relevant animal models.

PMID- 28753896
TI  - Reoperations for Female Stress Urinary Incontinence: A Finnish National Register
      Study.
AB  - BACKGROUND: Subjective and objective cure rates after primary surgery for female
      stress urinary incontinence are good. Still, some women will undergo repeated
      operations for incontinence. OBJECTIVE: To study the reoperation rate after
      incontinence surgery and to compare the reoperation rates between different
      surgery types. DESIGN, SETTING, AND PARTICIPANTS: This national register-based
      study included all Finnish women who had surgery for stress urinary incontinence
      during a 23-yr study period (1987-2009), both in inpatient and outpatient
      hospital settings. Subcohorts for follow-up times of 5-yr and 10-yr were
      evaluated separately. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary
      operations, reoperation rate, patient age, time until reoperation. RESULTS AND
      LIMITATIONS: A total of 38 500 women had surgery for stress urinary incontinence
      from 1987 to 2009. Two thousand and seventy-six women (7.2%) had a reoperation
      with a rate of 7.8/1000 woman-yr. The reoperation rate was 8.3/1000 women-yr
      after a Burch colposuspension and 4.8/1000 after a retropubic midurethral sling.
      In the 10-yr follow-up, reoperation was more common after a Burch compared with a
      retropubic midurethral sling (odds ratio: 1.6, 95% confidence interval: 1.3-1.9).
      There was no difference in the reoperation rate between retropubic and
      transobturator midurethral slings in the 5-yr follow-up. CONCLUSIONS: Reoperation
      rate is lower after midurethral slings compared with Burch colposuspension.
      PATIENT SUMMARY: Mesh slings are surgically effective treatments for stress
      urinary incontinence. There are fewer reoperations after implanting these slings
      compared with older methods that do not use synthetic material. Different mesh
      slings have equally good results.

PMID- 28753897
TI  - Lack of Effectiveness of Postchemotherapy Lymphadenectomy in Bladder Cancer
      Patients with Clinical Evidence of Metastatic Pelvic or Retroperitoneal Lymph
      Nodes Only: A Propensity Score-based Analysis.
AB  - BACKGROUND: Limited data is available on the role, and extent of,
      postchemotherapy lymphadenectomy (PC-LND) in patients with clinical evidence of
      pelvic (cN1-3) or retroperitoneal (RP) lymph node spread from urothelial bladder
      carcinoma. OBJECTIVE: To compare the outcomes of operated versus nonoperated
      patients after first-line chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: Data
      from 34 centers was collected, totaling 522 patients, treated between January
      2000 and June 2015. Criteria for patient selection were the following: bladder
      primary tumor, lymph node metastases (pelvic+/-RP) only, first-line platinum
      based chemotherapy given. INTERVENTION: LND (with cystectomy) versus observation
      after first-line chemotherapy for metastatic urothelial bladder carcinoma.
      OUTCOME MEASURES AND STATISTICAL ANALYSIS: Overall survival (OS) was the primary
      endpoint. Multiple propensity score techniques were adopted, including 1:1
      propensity score matching and inverse probability of treatment weighting.
      Additionally, the inverse probability of treatment weighting analysis was
      performed with the inclusion of the covariates, that is, with doubly robust
      estimation. RESULTS AND LIMITATIONS: Overall, 242 (46.4%) patients received PC
      LND and 280 (53.6%) observation after chemotherapy. There were 177 (33.9%) and
      345 (66.1%) patients with either RP or pelvic LND only, respectively. Doubly
      robust estimation-adjusted comparison was not significant for improved OS for PC
      LND (hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56-1.31, p=0.479),
      confirmed by matched analysis (HR: 0.91, 95% CI: 0.60-1.36, p=0.628). This was
      also observed in the RP subgroup (HR: 1.12, 95% CI: 0.68-1.84). The retrospective
      nature of the data and the heterogeneous patient population were the major
      limitations. CONCLUSIONS: Although there were substantial differences between the
      two groups, after accounting for major confounders we report a nonsignificant OS
      difference with PC-LND compared with observation only. These findings may be
      hypothesis-generating for future prospective trials. PATIENT SUMMARY: We found no
      differences in survival by adding postchemotherapy lymphadenectomy in patients
      with pelvic or retroperitoneal lymph node metastatic bladder cancer. The
      indication to perform postchemotherapy lymphadenectomy in the most suitable
      patients requires additional studies.

PMID- 28753898
TI  - Application of a spatially resolved model to contextualise monitoring data for
      risk assessment of down-the-drain chemicals over large scales.
AB  - Many regulatory screening level exposure assessments are based on simple large
      scale conceptual scenarios. However, exposure, and therefore risks associated
      with chemicals, are characterised by high spatial variability. The Scenario
      assembly tool (ScenAT) is a global screening level model to enable spatially
      resolved local predictions of environmental concentrations of home and personal
      care chemicals. It uses the European Union Technical Guidance Document (TGD)
      equation to predict local scale freshwater concentrations (predicted
      environmental concentrations - PECs) of chemicals discharged via wastewater.
      ScenAT uses Geographic Information System (GIS) layers for the underlying socio
      economic (population) and environmental parameters (per capita water use, sewage
      treatment plant connectivity, dilution factor). Using a probabilistic approach,
      we incorporate sources of uncertainty in the input data (tonnage estimation,
      removal in sewage treatment plants and seasonal variability in dilution factors)
      for two case-study chemicals: the antimicrobial triclosan (TCS) and the anionic
      surfactant linear alkylbenzene sulphonate (LAS). We then compare model estimates
      of wastewater and freshwater concentrations of TCS and LAS to UK monitoring data.
      Comparison showed that modeled PECs were on average higher than mean measured
      data for TCS and LAS by a factor 1.8 and 1.4, respectively. Considering the
      uncertainty associated with both model and monitoring data, the use of a
      probabilistic approach using the ScenAT model for screening assessment is
      reasonable. The combination of modelled and monitoring data enables the
      contextualisation of monitoring data. Spatial PECs can be used to identify areas
      of elevated concentration for further refined assessment.

PMID- 28753899
TI  - Below-cloud wet scavenging of soluble inorganic ions by rain in Beijing during
      the summer of 2014.
AB  - Wet deposition is one of the most important and efficient removal mechanisms in
      the reduction of air pollution. As a key parameter determining wet deposition,
      the wet scavenging coefficient (WSC) is widely used in chemical transport models
      (CTMs) and reported values have large uncertainties. In this study, a high
      resolution observational dataset of the soluble inorganic aerosols (SO42-, NO3-
      and NH4+, hereafter SNA) in the air and in rainwater during multiple
      precipitation events was collected using sequential sampling and used to estimate
      the below-cloud WSC in Beijing during the summer of 2014. The average
      concentrations of SNA in precipitation during the observational period were 7.9
      mg/L, 6.2 mg/L and 4.6 mg/L, with the contributions from below-cloud scavenging
      constituting 56%, 61% and 47% of this, respectively. The scavenging ratios of SNA
      (i.e., the ratio of the concentrations in rain to concentrations in the air) were
      used with the height of the cloud base and the precipitation intensity to
      estimate the WSC. The estimated WSC of SO42- is comparable to that reported
      elsewhere. The relationship between the below-cloud WSC and the precipitation
      intensity followed an exponential power distribution (K=aPb) for SNA. In contrast
      to previous studies, this study considers the differences between the chemical
      compositions of the SNA, with the highest WSC for NO3-, followed by those of SO42
      and NH4+. Therefore, we recommend that CTMs include ion specific WSCs in the
      future.

PMID- 28753900
TI  - Short-term effects of ambient air pollution on emergency room admissions due to
      cardiovascular causes in Beijing, China.
AB  - Ambient air pollution has been a major global public health issue. A number of
      studies have shown various adverse effects of ambient air pollution on
      cardiovascular diseases. In the current study, we investigated the short-term
      effects of ambient air pollution on emergency room (ER) admissions due to
      cardiovascular causes in Beijing from 2009 to 2012 using a time-series analysis.
      A total of 82430 ER cardiovascular admissions were recorded. Different gender
      (male and female) and age groups (15yrs <= age <65 yrs and age >= 65 yrs) were
      also examined by single model and multiple-pollutant model. Three major
      pollutants (SO2, NO2 and PM10) had lag effects of 0-2 days on cardiovascular ER
      admissions. The relative risks (95% CI) of per 10 MUg/m3 increase in PM10, SO2
      and NO2 were 1.008 (0.997-1.020), 1.008(0.999-1.018) and 1.014(1.003-1.024),
      respectively. The effect was more pronounced in age >=65 and males in Beijing. We
      also found the stronger acute effects on the elderly and females at lag 0 than on
      the younger people and males at lag 2.

PMID- 28753901
TI  - Determining the distribution of pharmaceutically active compounds (PhACs) in
      soils and sediments by pressurized hot water extraction (PHWE).
AB  - The occurrence of pharmaceutically active compounds (PhACs) in the environment
      may pose a potential risk for humans and ecosystems. Wastewater treatment plants
      (WWTPs) are recognized as one of the main sources of these chemicals into both
      aquatic and terrestrial environments. The objectives of the study were to
      determine the presence of a wide variety of PhACs (n = 45) in sewage-impacted
      sediments and soils from the Guadalete River basin (SW Spain) by developing and
      applying an environmentally friendly multi-residue method based on pressurized
      hot water extraction (PHWE). Different parameters were optimized, including
      extraction temperature, pH, solvents, and clean-up. Extraction recoveries were
      analyte dependent, varying between 50% and 140% for most of the analytes when
      using pure water as extraction solvent at 100  degrees C. Determination of PhACs
      was performed by ultra-high performance liquid chromatography - tandem mass
      spectrometry (UPLC-MS/MS), enabling method detection (mLODs) and quantification
      (mLOQs) limits between <0.01 and 0.83 ng g-1 and from 0.02 to 2.75 ng g-1,
      respectively. Regarding the sampling area, 14 out of 45 target compounds were
      detected in soils and sediments. Analgesic/anti-inflammatories was the
      therapeutic group most commonly detected, reaching concentrations up to 20 ng g
      1.

PMID- 28753902
TI  - Environmental assessment of the effects of a municipal landfill on the content
      and distribution of heavy metals in Tanacetum vulgare L.
AB  - Heavy metal pollution is an important concern because of its potential to affect
      human health. This study was conducted to analyze plants growing on a landfill
      body and in its surroundings to determine their potential for heavy metal
      accumulation. In addition, the enrichment coefficient (EC) for the plant/soil
      system was used for determining the environmental contamination from a landfill
      in terms of heavy metal accumulation. The samples were taken in 2013-2014. Of the
      analyzed metals, iron achieved the highest values in the samples, i.e. - stalk
      (103.4-6564.6 mg/kg DM), roots (6563.6-33,036.6 mg/kg DM), leaf (535.1-11,275
      mg/kg DM) and soil (12,389-39,381.9 mg/kg DM). The highest concentrations were
      determined in 2013 for Fe, Mn and Zn. Iron achieved the highest concentrations in
      the years 2013-2014. Next, EC values were then calculated, with the highest noted
      for Cd. Cd, as well as Cr, Ni and Zn are accumulated mostly in the leaves,
      whereas Co, Cu, Fe, Hg, Mn and Pb are accumulated mainly in the roots of T.
      vulgare.

PMID- 28753903
TI  - Can an aquatic macrophyte bioaccumulate glyphosate? Development of a new method
      of glyphosate extraction in Ludwigia peploides and watershed scale validation.
AB  - Glyphosate is intensively used in agricultural fields and it is frequently
      detected in non-target wetland ecosystems. The floating hydrophyte Ludwigia
      peploides is widely distributed in American streams and it is an abundant
      species. Therefore, our objectives were (1) to establish and validate an
      extraction and quantification methodology for glyphosate in L. peploides and (2)
      to evaluate the role of this species as a potential glyphosate biomonitor in an
      agricultural watershed. We developed a new method of glyphosate extraction from
      leaves of L. peploides. The method recovery was 117+/- 20% and the matrix effect
      20%. To validate the method using environmental samples, plants of L. peploides
      were collected in March 2016 from eight monitoring sites of El Crespo stream.
      Surface water and sediment samples were collected at the same time to measure
      glyphosate and to calculate bioconcentration factors (BCFs) and biota-sediment
      accumulation factors (BSAFs). Glyphosate was detected in 94.11% in leaves, the
      concentrations ranging between 4 and 108 MUg/kg. Glyphosate was detected in
      surface water and sediments at 75% and 100% of the samples, at concentrations
      that varied between 0 and 1.7 MUg/L and 5-10.50 MUg/kg dry weight, respectively.
      The mean BCFs and BSAFs were 88.10 L/Kg and 7.61, respectively. These results
      indicate that L. peploides bioaccumulates glyphosate mainly bioavailable in the
      surface water. In this sense, L. peploides could be used as a biomonitor organism
      to evaluate glyphosate levels in freshwater aquatic ecosystems because, in
      addition to its capacity to bioconcentrate glyphosate, it is easy to sample and
      it has a restricted mobility.

PMID- 28753904
TI  - Inhibitory effects of fifteen phthalate esters in human cDNA-expressed UDP
      glucuronosyltransferase supersomes.
AB  - Phthalate esters (PAEs) have been extensively used in industry as plasticizers
      and there remains concerns about their safety. The present study aimed to
      determine the inhibition of phthalate esters (PAEs) on the activity of the phase
      II drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). In vitro
      recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone was used to
      investigate the inhibition potentials of PAEs towards various s UGTs. PAEs
      exhibited no significant inhibition of UGT1A1, UGT1A3, UGT1A8, UGT1A10, UGT2B15,
      and UGT2B17, and limited inhibition of UGT1A6, UGT1A7 and UGT2B4. However, UGT1A9
      was strongly inhibited by PAEs. In silico docking demonstrated a significant
      contribution of hydrogen bonds and hydrophobic interactions contributing to the
      inhibition of UGT by PAEs. The Ki values were 15.5, 52.3, 23.6, 12.2, 5.61, 2.79,
      1.07, 22.8, 0.84, 73.7, 4.51, 1.74, 0.58, 6.79, 4.93, 6.73, and 7.23 MUM for BBOP
      UGT1A6, BBZP-UGT1A6, BBOP-UGT1A7, BBZP-UGT1A7, DiPP-UGT1A9, DiBP-UGT1A9, DCHP
      UGT1A9, DBP-UGT1A9, BBZP-UGT1A9, BBOP-UGT1A9, DMEP-UGT1A9, DPP-UGT1A9, DHP
      UGT1A9, DiBP-UGT2B4, DBP-UGT2B4, DAP-UGT2B4, and BBZP-UGT2B4, respectively. In
      conclusion, exposure to PAEs might influence the metabolic elimination of
      endogenous compounds and xenobiotics through inhibiting UGTs.

PMID- 28753905
TI  - Efficient removal and environmentally benign detoxification of Cr(VI) in aqueous
      solutions by Zr(IV) cross-linking chitosan magnetic microspheres.
AB  - Zirconium(IV) cross-linking chitosan (CTS) magnetic microspheres (Fe3O4@Zr-CTS)
      as a recoverable adsorbent were synthesized through the coordination reaction
      between zirconium oxychloride and CTS biopolymeric matrix for efficient
      adsorption and simultaneous detoxification of hexavalent chromium, Cr(VI), in
      aqueous solutions. Scanning electron microscopy (SEM) and X-ray diffraction (XRD)
      confirmed the formation of core@shell magnetite microspheres. X-ray photoelectron
      spectroscopy (XPS), and Fourier transform infrared spectroscopy (FT-IR) verified
      the crosslinking of Zr(IV) to CTS on the microspheres. Batch Cr(VI) adsorption
      performances of the resultant Fe3O4@Zr-CTS microspheres revealed that the maximum
      adsorption capacity of 280.97 mg/g were achieved under pH 4.0 at 298 K. The XPS
      analyses indicated that 61.1% of the adsorbed Cr(VI) was reduced to Cr(III) due
      to the oxidization of alcoholic groups on C-6 in CTS which served as electron
      donors to carbonyl groups. The adsorbent showed preferential Cr(VI) adsorption
      with the existence of co-existing cations (K+, Na+, Cu2+, Zn2+, Ca2+, Mg2+) and
      anions (NO3-, Cl-, SO42-, CO32-). The adsorbent exhibited excellent reusability,
      lower the effluent Cr(VI) contents down to the ppb level, which satisfied the
      drinking water standard recommended by the World Health Organization and was a
      promising candidate for water purification.

PMID- 28753906
TI  - Dexmedetomidine preconditioning plays a neuroprotective role and suppresses
      TLR4/NF-kappaB pathways model of cerebral ischemia reperfusion.
AB  - BACKGROUND: Dexmedetomidine has been reported to play an efficient role on multi
      organ protection. Our study aims to investigate the neuroprotective of
      dexmedetomidine preconditioning on cerebral ischemic reperfusion (I/R) injury and
      investigate the underlining signaling mechanisms. METHODS: Cerebral I/R models
      were established with SD rats through middle cerebral artery occlusion (MCAO).
      After 2h of ischemia followed by 7days of reperfusion, the degree of cerebral
      tissue injury was detected by HE, Nissl and TUNEL staining. Glial fibrillary
      acidic protein (GFAP) positive and TNF-alpha positive cells were stained by
      immunohistochemistry and counted under microscope. TLR4, NF-kappaB and TIR-domain
      containing adapter-inducing interferon-beta (TRIF) expression were detected by
      real time PCR and western blot. RESULTS: Dexmedetomidine preconditioning markedly
      prevented the ischemia-induced cellular damage observed from HE and Nissl
      staining in hippocampus and cortex. Dexmedetomidine observably decreased the
      number of apoptotic cells in TUNEL staining. Besides, yohimbine could
      specifically suppress the protective effect of dexmedetomidine. GFAP expression
      was distinctly inhibited by dexmedetomidine preconditioning (10MUg/kg, 20MUg/kg)
      in cerebral ischemia area. Dexmedetomidine preconditioning inhibited the
      expression of TLR4 and NF-kappaB and increased that of TRIF. CONCLUSION: The
      results of this study suggest that dexmedetomidine preconditioning plays a
      neuroprotective role against I/R injury. Dexmedetomidine might suppress TLR4/NF
      ??B pathway and drive TLR4/TRIF signaling pathway to reduce the inflammatory
      injury.

PMID- 28753907
TI  - Shikonin ameliorates isoproterenol (ISO)-induced myocardial damage through
      suppressing fibrosis, inflammation, apoptosis and ER stress.
AB  - Shikonin, isolated from the roots of herbal plant Lithospermum erythrorhizon, is
      a naphthoquinone. It has been reported to exert beneficial anti-inflammatory
      effects and anti-oxidant properties in various diseases. Isoproterenol (ISO) has
      been widely used to establish cardiac injury in vivo and in vitro. However,
      shikonin function in ISO-induced cardiac injury remains uncertain. In our study,
      we attempted to investigate the efficiency and possible molecular mechanism of
      shikonin in cardiac injury treatment induced by ISO. In vivo, C57BL6 mice were
      subcutaneously injected with 5mg/kg ISO to induce heart failure. And mice were
      given a gavage of shikonin (2 or 4mg/kg/d, for four weeks). Cardiac function,
      fibrosis indices, inflammation response, apoptosis and endoplasmic reticulum (ER)
      stress were calculated. Pathological alterations, fibrosis-, inflammation-,
      apoptosis- and ER stress-related molecules were examined. In ISO-induced cardiac
      injury, shikonin significantly ameliorated heart function, decreased myocardial
      fibrosis, suppressed inflammation, attenuated apoptosis and ER stress through
      impeding collagen accumulation, Toll like receptor 4/nuclear transcription factor
      kappaB (TLR4/NF-kappaB), Caspase-3 and glucose-regulated protein 78 (GRP78)
      signaling pathways activity, relieving heart failure in vivo. Also, in vitro,
      shikonin attenuated ISO-induced cardiac muscle cells by reducing fibrosis,
      inflammation, apoptosis and ER stress. Our findings indicated that shikonin
      treatment attenuated ISO-induced heart injury, providing an effective therapeutic
      strategy for heart failure treatment for future.

PMID- 28753908
TI  - Correction: Asthma and the risk of lung cancer: a meta-analysis.

PMID- 28753909
TI  - Correction: Hypermethylation of the CHRDL1 promoter induces proliferation and
      metastasis by activating Akt and Erk in gastric cancer.

PMID- 28753910
TI  - Practical Use of Metal Oxide Semiconductor Gas Sensors for Measuring Nitrogen
      Dioxide and Ozone in Urban Environments.
AB  - The potential of inexpensive Metal Oxide Semiconductor (MOS) gas sensors to be
      used for urban air quality monitoring has been the topic of increasing interest
      in the last decade. This paper discusses some of the lessons of three years of
      experience working with such sensors on a novel instrument platform (Small Open
      General purpose Sensor (SOGS)) in the measurement of atmospheric nitrogen dioxide
      and ozone concentrations. Analytic methods for increasing long-term accuracy of
      measurements are discussed, which permit nitrogen dioxide measurements with 95%
      confidence intervals of 20.0 MU g m - 3 and ozone precision of 26.8 MU g m - 3 ,
      for measurements over a period one month away from calibration, averaged over 18
      months of such calibrations. Beyond four months from calibration, sensor drift
      becomes significant, and accuracy is significantly reduced. Successful
      calibration schemes are discussed with the use of controlled artificial
      atmospheres complementing deployment on a reference weather station exposed to
      the elements. Manufacturing variation in the attributes of individual sensors are
      examined, an experiment possible due to the instrument being equipped with pairs
      of sensors of the same kind. Good repeatability (better than 0.7 correlation)
      between individual sensor elements is shown. The results from sensors that used
      fans to push air past an internal sensor element are compared with mounting the
      sensors on the outside of the enclosure, the latter design increasing effective
      integration time to more than a day. Finally, possible paths forward are
      suggested for improving the reliability of this promising sensor technology for
      measuring pollution in an urban environment.

PMID- 28753911
TI  - Morphological and Molecular Basis of Cytoplasmic Dilation and Swelling in
      Cortical Migrating Neurons.
AB  - During corticogenesis, neuronal migration is an essential step for formation of a
      functional brain, and abnormal migration is known to cause various neurological
      disorders. Neuronal migration is not just a simple movement of the cell body, but
      a consequence of various morphological changes and coordinated subcellular
      events. Recent advances in in vivo and ex vivo cell biological approaches, such
      as in utero gene transfer, slice culture and ex vivo chemical inhibitor
      techniques, have revealed details of the morphological and molecular aspects of
      neuronal migration. Migrating neurons have been found to have a unique structure,
      dilation or swelling, at the proximal region of the leading process; this
      structure is not found in other migrating cell types. The formation of this
      structure is followed by nuclear deformation and forward movement, and
      coordination of this three-step sequential morphological change (the
      dilation/swelling formation, nuclear elongation and nuclear movement) is
      essential for proper neuronal migration and the construction of a functional
      brain structure. In this review, we will introduce the morphological features of
      this unique structure in migrating neurons and summarize what is known about the
      molecules regulating the dilation/swelling formation and nuclear deformation and
      movement.

PMID- 28753912
TI  - Study on Finite Element Model Updating in Highway Bridge Static Loading Test
      Using Spatially-Distributed Optical Fiber Sensors.
AB  - A finite model updating method that combines dynamic-static long-gauge strain
      responses is proposed for highway bridge static loading tests. For this method,
      the objective function consisting of static long-gauge stains and the first order
      modal macro-strain parameter (frequency) is established, wherein the local
      bending stiffness, density and boundary conditions of the structures are selected
      as the design variables. The relationship between the macro-strain and local
      element stiffness was studied first. It is revealed that the macro-strain is
      inversely proportional to the local stiffness covered by the long-gauge strain
      sensor. This corresponding relation is important for the modification of the
      local stiffness based on the macro-strain. The local and global parameters can be
      simultaneously updated. Then, a series of numerical simulation and experiments
      were conducted to verify the effectiveness of the proposed method. The results
      show that the static deformation, macro-strain and macro-strain modal can be
      predicted well by using the proposed updating model.

PMID- 28753913
TI  - Multifunctional Water Sensors for pH, ORP, and Conductivity Using Only
      Microfabricated Platinum Electrodes.
AB  - Monitoring of the pH, oxidation-reduction-potential (ORP), and conductivity of
      aqueous samples is typically performed using multiple sensors. To minimize the
      size and cost of these sensors for practical applications, we have investigated
      the use of a single sensor constructed with only bare platinum electrodes
      deposited on a glass substrate. The sensor can measure pH from 4 to 10 while
      simultaneously measuring ORP from 150 to 800 mV. The device can also measure
      conductivity up to 8000 MUS/cm in the range of 10  degrees C to 50  degrees C,
      and all these measurements can be made even if the water samples contain common
      ions found in residential water. The sensor is inexpensive (i.e., ~$0.10/unit)
      and has a sensing area below 1 mm2, suggesting that the unit is cost-efficient,
      robust, and widely applicable, including in microfluidic systems.

PMID- 28753914
TI  - Surface Estimation for Microwave Imaging.
AB  - Biomedical imaging and sensing applications in many scenarios demand accurate
      surface estimation from a sparse set of noisy measurements. These measurements
      may arise from a variety of sensing modalities, including laser or
      electromagnetic samples of an object's surface. We describe a state-of-the-art
      microwave imaging prototype that has sensors to acquire both microwave and laser
      measurements. The approach developed to translate sparse samples of the breast
      surface into an accurate estimate of the region of interest is detailed. To
      evaluate the efficacy of the method, laser and electromagnetic samples are
      acquired by sensors from three realistic breast models with varying sizes and
      shapes. A set of metrics is developed to assist with the investigation and
      demonstrate that the algorithm is able to accurately estimate the shape of a
      realistic breast phantom when only a sparse set of data are available. Moreover,
      the algorithm is robust to the presence of measurement noise, and is effective
      when applied to measurement scans of patients acquired with the prototype.

PMID- 28753915
TI  - Colorful Packages: Encapsulation of Fluorescent Proteins in Complex Coacervate
      Core Micelles.
AB  - Encapsulation of proteins can be beneficial for food and biomedical applications.
      To study their biophysical properties in complex coacervate core micelles (C3Ms),
      we previously encapsulated enhanced green fluorescent protein (EGFP) and its
      monomeric variant, mEGFP, with the cationic-neutral diblock copolymer poly(2
      methyl-vinyl-pyridinium)n-b-poly(ethylene-oxide)m (P2MVPn-b-PEOm) as enveloping
      material. C3Ms with high packaging densities of fluorescent proteins (FPs) were
      obtained, resulting in a restricted orientational freedom of the protein
      molecules, influencing their structural and spectral properties. To address the
      generality of this behavior, we encapsulated seven FPs with P2MVP41-b-PEO205 and
      P2MVP128-b-PEO477. Dynamic light scattering and fluorescence correlation
      spectroscopy showed lower encapsulation efficiencies for members of the Anthozoa
      class (anFPs) than for Hydrozoa FPs derived from Aequorea victoria (avFPs). Far
      UV CD spectra of the free FPs showed remarkable differences between avFPs and
      anFPs, caused by rounder barrel structures for avFPs and more elliptic ones for
      anFPs. These structural differences, along with the differences in charge
      distribution, might explain the variations in encapsulation efficiency between
      avFPs and anFPs. Furthermore, the avFPs remain monomeric in C3Ms with minor
      spectral and structural changes. In contrast, the encapsulation of anFPs gives
      rise to decreased quantum yields (monomeric Kusabira Orange 2 (mKO2) and Tag red
      fluorescent protein (TagRFP)) or to a pKa shift of the chromophore (FP variant
      mCherry).

PMID- 28753916
TI  - Zinc Oxide-Based Self-Powered Potentiometric Chemical Sensors for Biomolecules
      and Metal Ions.
AB  - Advances in the miniaturization and portability of the chemical sensing devices
      have always been hindered by the external power supply problem, which has focused
      new interest in the fabrication of self-powered sensing devices for disease
      diagnosis and the monitoring of analytes. This review describes the fabrication
      of ZnO nanomaterial-based sensors synthesized on different conducting substrates
      for extracellular detection, and the use of a sharp borosilicate glass capillary
      (diameter, d = 700 nm) to grow ZnO nanostructures for intracellular detection
      purposes in individual human and frog cells. The electrocatalytic activity and
      fast electron transfer properties of the ZnO materials provide the necessary
      energy to operate as well as a quick sensing device output response, where the
      role of the nanomorphology utilized for the fabrication of the sensor is crucial
      for the production of the operational energy. Simplicity, design, cost,
      sensitivity, selectivity and a quick and stable response are the most important
      features of a reliable sensor for routine applications. The review details the
      extra- and intra-cellular applications of the biosensors for the detection and
      monitoring of different metallic ions present in biological matrices, along with
      the biomolecules glucose and cholesterol.

PMID- 28753917
TI  - Mining Feature of Data Fusion in the Classification of Beer Flavor Information
      Using E-Tongue and E-Nose.
AB  - Multi-sensor data fusion can provide more comprehensive and more accurate
      analysis results. However, it also brings some redundant information, which is an
      important issue with respect to finding a feature-mining method for intuitive and
      efficient analysis. This paper demonstrates a feature-mining method based on
      variable accumulation to find the best expression form and variables' behavior
      affecting beer flavor. First, e-tongue and e-nose were used to gather the taste
      and olfactory information of beer, respectively. Second, principal component
      analysis (PCA), genetic algorithm-partial least squares (GA-PLS), and variable
      importance of projection (VIP) scores were applied to select feature variables of
      the original fusion set. Finally, the classification models based on support
      vector machine (SVM), random forests (RF), and extreme learning machine (ELM)
      were established to evaluate the efficiency of the feature-mining method. The
      result shows that the feature-mining method based on variable accumulation
      obtains the main feature affecting beer flavor information, and the best
      classification performance for the SVM, RF, and ELM models with 96.67%, 94.44%,
      and 98.33% prediction accuracy, respectively.

PMID- 28753918
TI  - The Anti-Inflammatory Properties of Citrus wilsonii Tanaka Extract in LPS-Induced
      RAW 264.7 and Primary Mouse Bone Marrow-Derived Dendritic Cells.
AB  - 'Zhique' (Citrus wilsonii Tanaka) is a traditional Chinese medicine. Its fruits
      have been used to treat inflammation-related symptoms, such as cough and sputum,
      though the underlying mechanism remains poorly understood. The aim of this study
      was to investigate the anti-inflammatory properties of 'Zhique' pulp extract
      (ZQE) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and primary mouse
      bone marrow-derived dendritic cells (BMDCs). The flavonoid profiles of the ZQE
      were determined by high performance liquid chromatography. The anti-inflammatory
      activity was evaluated in LPS-induced inflammatory RAW 264.7 macrophages and
      BMDCs through enzyme-linked immunosorbent assay, quantitative real-time
      polymerase chain reaction, and Western blot assays. Naringin was a predominant
      flavonoid occurring in ZQE, followed by eriocitrin, hesperidin, neohesperidin,
      rhoifolin, naringenin, and poncirin. ZQE exhibited a very low cytotoxicity in LPS
      stimulated RAW 264.7 macrophages. Meanwhile, ZQE significantly inhibited the
      production of prostaglandins E2 and secretion of cyclooxygenase-2 protein in LPS
      stimulated RAW 264.7 macrophages, and markedly suppressed the mRNA expression of
      inflammatory mediators, such as cyclooxygenase-2, tumor necrosis factor alpha,
      interleukin-1 beta (IL-1beta), and IL-6 in LPS-induced RAW 264.7 macrophages
      and/or primary BMDCs. The ZQE inhibited the inflammatory responses in RAW 264.7
      macrophages and BMDCs triggered by LPS. The results suggested that 'Zhique' has a
      high potential as a novel therapeutic agent to treat chronic inflammatory
      diseases.

PMID- 28753919
TI  - As(V) Sorption/Desorption on Different Waste Materials and Soil Samples.
AB  - Aiming to investigate the efficacy of different materials as bio-sorbents for the
      purification of As-polluted waters, batch-type experiments were employed to study
      As(V) sorption and desorption on oak ash, pine bark, hemp waste, mussel shell,
      pyritic material, and soil samples, as a function of the As(V) concentration
      added. Pyritic material and oak ash showed high sorption (90% and >87%) and low
      desorption (<2% and <7%). Alternatively, hemp waste showed low retention (16%
      sorption and 100% desorption of the amount previously sorbed), fine shell and
      pine bark sorbed <3% and desorbed 100%, the vineyard soil sample sorbed 8% and
      released 85%, and the forest soil sample sorbed 32% and desorbed 38%. Sorption
      data fitted well to the Langmuir and Freundlich models in the case of both soil
      samples and the pyritic material, but only to the Freundlich equation in the case
      of the various by-products. These results indicate that the pyritic material and
      oak ash can be considered efficient As(V) sorbents (thus, useful in remediation
      of contaminated sites and removal of that pollutant), even when As(V)
      concentrations up to 6 mmol L-1 are added, while the other materials that were
      tested cannot retain or remove As(V) from polluted media.

PMID- 28753920
TI  - Evaluating Otto the Auto: Does Engagement in an Interactive Website Improve Young
      Children's Transportation Safety?
AB  - Transportation-related injuries are a leading cause of pediatric death, and
      effective interventions are limited. Otto the Auto is a website offering
      engaging, interactive activities. We evaluated Otto among a sample of sixty-nine
      4- and 5-year-old children, who participated in a randomized parallel group
      design study. Following baseline evaluation, children engaged with either Otto or
      a control website for 2 weeks and then were re-evaluated. Children who used Otto
      failed to show increases in transportation safety knowledge or behavior compared
      to the control group, although there was a dosage effect whereby children who
      engaged in the website more with parents gained safer behavior patterns. We
      conclude Otto may have some efficacy when engaged by children with their parents,
      but continued efforts to develop and refine engaging, effective, theory-driven
      strategies to teach children transportation safety, including via internet,
      should be pursued.

PMID- 28753921
TI  - Comparison of Annoyance from Railway Noise and Railway Vibration.
AB  - The aim of this study is to compare vibration exposure to noise exposure from
      railway traffic in terms of equal annoyance, i.e., to determine when a certain
      noise level is equally annoying as a corresponding vibration velocity. Based on
      questionnaire data from the Train Vibration and Noise Effects (TVANE) research
      project from residential areas exposed to railway noise and vibration, the dose
      response relationship for annoyance was estimated. By comparing the relationships
      between exposure and annoyance for areas both with and without significant
      vibration exposure, the noise levels and vibration velocities that had an equal
      probability of causing annoyance was determined using logistic regression. The
      comparison gives a continuous mapping between vibration velocity in the ground
      and a corresponding noise level at the facade that are equally annoying. For
      equivalent noise level at the facade compared to maximum weighted vibration
      velocity in the ground the probability of annoyance is approximately 20% for 59
      dB or 0.48 mm/s, and about 40% for 63 dB or 0.98 mm/s.

PMID- 28753923
TI  - An Overview of Seafood Supply, Food Safety and Regulation in New South Wales,
      Australia.
AB  - Seafood consumption is increasing in Australia, especially in New South Wales
      (NSW). Average per capita seafood consumption in NSW is higher than the national
      average. Seafood supply in NSW comes from domestic (wild catch and aquaculture)
      and overseas (seafood imports) sources. The contribution of wild catch and
      aquaculture in domestic seafood production (2012-2013) was 73.42% and 26.52%,
      respectively. Seafood-associated foodborne illness outbreaks are not common and
      on an average four outbreaks occur each year in NSW. Most of the outbreaks in
      2015 and 2016 were related to ciguatera poisoning. The regulation of the seafood
      industry and the management of food safety is an example of the coordinated work
      of multiple government agencies and organizations in which NSW Food Authority is
      responsible for managing the overall risks through the Seafood Safety Scheme.
      Overall, seafood supply in NSW is of high quality and poses low food safety risk
      to consumers.

PMID- 28753922
TI  - Evidence of Oxidative Stress and Secondary Mitochondrial Dysfunction in Metabolic
      and Non-Metabolic Disorders.
AB  - Mitochondrial dysfunction and oxidative stress have been implicated in the
      pathogenesis of a number of diseases and conditions. Oxidative stress occurs once
      the antioxidant defenses of the body become overwhelmed and are no longer able to
      detoxify reactive oxygen species (ROS). The ROS can then go unchallenged and are
      able to cause oxidative damage to cellular lipids, DNA and proteins, which will
      eventually result in cellular and organ dysfunction. Although not always the
      primary cause of disease, mitochondrial dysfunction as a secondary consequence
      disease of pathophysiology can result in increased ROS generation together with
      an impairment in cellular energy status. Mitochondrial dysfunction may result
      from either free radical-induced oxidative damage or direct impairment by the
      toxic metabolites which accumulate in certain metabolic diseases. In view of the
      importance of cellular antioxidant status, a number of therapeutic strategies
      have been employed in disorders associated with oxidative stress with a view to
      neutralising the ROS and reactive nitrogen species implicated in disease
      pathophysiology. Although successful in some cases, these adjunct therapies have
      yet to be incorporated into the clinical management of patients. The purpose of
      this review is to highlight the emerging evidence of oxidative stress, secondary
      mitochondrial dysfunction and antioxidant treatment efficacy in metabolic and non
      metabolic diseases in which there is a current interest in these parameters.

PMID- 28753924
TI  - Omega-3 Polyunsaturated Fatty Acids for the Treatment of IgA Nephropathy.
AB  - IgA nephropathy is a common disease that causes end-stage renal failure and
      requires renal replacement therapy. The main purpose of therapeutic intervention
      in this disease is not limited to improvement of prognosis and prevention of
      transition to end-stage renal failure, but also prevention of the occurrence of
      cardiovascular lesions, which increases risk in patients with chronic kidney
      disease. Steroids and immunosuppressants have been widely used as remission
      induction therapies; however, the balance between their therapeutic benefits and
      detrimental side-effects are controversial. In this regard, it is critical to
      identify alternative therapies which would provide holistic life-long benefits.
      Currently, the potential of omega-3 fatty acids as anti-inflammatory and
      inflammation-convergent drugs-especially the remarkable progress of the
      multifunctional omega-3 polyunsaturated fatty acids (PUFAs)-has garnered
      attention. In this section, we outline the background and current status of omega
      3 PUFA-based treatment in IgA nephropathy.

PMID- 28753925
TI  - Pilot Study Using a Chitosan-Hydroxyapatite Implant for Guided Alveolar Bone
      Growth in Patients with Chronic Periodontitis.
AB  - Periodontitis is an infectious and inflammatory disease associated with
      significant loss of alveolar crest and soft tissue attached to the teeth.
      Chitosan and hydroxyapatite are biomaterials used for bone tissue repair because
      of their biodegradability and biocompatibility in nature. The present study
      evaluated the effects of chitosan (CH) in combination with hydroxyapatite (HAP)
      to promote alveolar bone growth. A chitosan implant mixed with hydroxyapatite was
      implanted into the affected area of 9 patients suffering chronic periodontitis.
      Patients were evaluated through X-ray images and a millimetric slide over a one
      year period. The application of CH/HAP produced an average alveolar bone growth
      of 5.77 mm (+/-1.87 mm). At the onset of the study, the dental pocket exhibited a
      depth level (DPDL) of 8.66 mm and decreased to 3.55 mm one year after the
      implant. Tooth mobility grade was 2.44 mm at the onset and 0.8 mm at the end of
      the study with a significant difference of p < 0.001. Moreover, the bone density
      in the affected areas was similar to the density of the bone adjacent to it. This
      result was confirmed with the software implant viewer from Anne Solutions
      Company. In conclusion, the CH/HAP implant promoted alveolar bone growth in
      periodontitis patients.

PMID- 28753926
TI  - The Prostaglandin EP3 Receptor Is an Independent Negative Prognostic Factor for
      Cervical Cancer Patients.
AB  - We know that one of the main risk factors for cervical cancer is an infection
      with high-risk human papillomavirus (HR-HPV). Prostaglandins and their receptors
      are very important for the tumour growth and tumour-associated angiogenesis.
      Little is known about the expression of the Prostaglandin E receptor type 3 (EP3)
      or the Prostaglandin (PG)E2-EP3 signalling in cervical cancer, so the aim of the
      study was to analyse the expression of the EP3 receptor in cervical cancer and
      find prognostic factors in relation to survival; EP3 immunohistological staining
      of 250 cervical cancer slides was performed and analysed with a semi-quantitative
      score. The statistical evaluation was performed with Statistical Package for the
      Social Sciences (SPSS) to evaluate the staining results and the survival analyses
      of the cervical cancer cases. A significant difference was observed in EP3
      expression in Federation Internationale de Gynecologie et d'Obstetrique (FIGO)
      stadium I versus FIGO stadium II-IV cases. High expression of EP3 (IRS >= 1.5) in
      cervical cancer patients was correlated with poor prognosis in overall survival
      rates. Survival in adenocarcinoma (AC) of the cervix was lower than in squamous
      cell carcinoma (SCC). Cox regression analysis shows that EP3 is an independent
      prognosticator. In this study we could show that the membrane-bound prostaglandin
      receptor EP3 is an independent prognosticator for cervical cancer patient
      survival. Targeting the EP3 receptor seems to be an interesting candidate for
      endocrine therapy. Therefore, more research is needed on the influence of the
      receptor system and its influence on cervical cancer growth.

PMID- 28753927
TI  - Self-Reported Non-Celiac Wheat Sensitivity in High School Students: Demographic
      and Clinical Characteristics.
AB  - BACKGROUND: Non-Celiac Wheat Sensitivity (NCWS) has recently been included among
      the gluten-related disorders. As no biomarkers of this disease exist, its
      frequency has been estimated based on self-reported symptoms, but to date no data
      are available about self-reported NCWS in teenagers. AIM: To explore the
      prevalence of self-reported NCWS in a group of high school students and to study
      their demographic and clinical characteristics. METHODS: The study was performed
      between April 2015 and January 2016 in two high schools of a coastal town in the
      south of Sicily (Italy). A total of 555 students (mean age 17 years, 191 male,
      364 female) completed a modified validated questionnaire for self-reported NCWS.
      The subjects who self-reported NCWS were then compared with all the others.
      RESULTS: Seven individuals (1.26%) had an established diagnosis of CD. The
      prevalence of self-reported NCWS was 12.2%, and 2.9% were following a gluten-free
      diet (GFD). Only 15 out of 68 (23%) NCWS self-reporters had consulted a doctor
      for this problem and only nine (14%) had undergone serological tests for celiac
      disease. The NCWS self-reporters very often had IBS symptoms (44%). CONCLUSIONS:
      Self-reported NCWS was found to be common in teenagers, with a frequency of
      12.2%; the frequency of GFD use was 2.9%, which was much higher than the
      percentage of known CD in the same population (1.26%). A greater awareness of the
      possible implications on the part of the subjects involved, and a more thorough
      medical approach to the study of self-reported wheat-induced symptoms are
      required.

PMID- 28753928
TI  - N-Heterocyclic Carbene Coinage Metal Complexes of the Germanium-Rich Metalloid
      Clusters [Ge9R3]- and [Ge9RI2]2- with R = Si(iPr)3 and RI = Si(TMS)3.
AB  - We report on the synthesis of novel coinage metal NHC (N-heterocyclic carbene)
      compounds of the germanium-rich metalloid clusters [Ge9R3]- and [Ge9RI2]2- with R
      = Si(iPr)3 and RI = Si(TMS)3. NHCDippCu{eta3Ge9R3} with R = Si(iPr)3 (1)
      represents a less bulky silyl group-substituted derivative of the known analogous
      compounds with R = Si(iBu)3 or Si(TMS)3. The coordination of the [NHCDippCu]+
      moiety to the cluster unit occurs via one triangular face of the tri-capped
      trigonal prismatic [Ge9] cluster. Furthermore, a series of novel Zintl cluster
      coinage metal NHC compounds of the type (NHCM)2{eta3Ge9RI2} (RI = Si(TMS)3 M =
      Cu, Ag and Au; NHC = NHCDipp or NHCMes) is presented. These novel compounds
      represent a new class of neutral dinuclear Zintl cluster coinage metal NHC
      compounds, which are obtained either by the stepwise reaction of a suspension of
      K12Ge17 with Si(TMS)3Cl and the coinage metal carbene complexes NHCMCl (M = Cu,
      Ag, Au), or via a homogenous reaction using the preformed bis-silylated cluster
      K2[Ge9(Si(TMS)3)2] and the corresponding NHCMCl (M = Cu, Ag, Au) complex. The
      molecular structures of NHCDippCu{eta3Ge9(Si(iPr)3)3} (1) and (NHCDippCu)2{eta3
      Ge9(Si(TMS)3)2} (2) were determined by single crystal X-ray diffraction methods.
      In 2, the coordination of the [NHCDippCu]+ moieties to the cluster unit takes
      place via both open triangular faces of the [Ge9] entity. Furthermore, all
      compounds were characterized by means of NMR spectroscopy (1H, 13C, 29Si) and ESI
      MS.

PMID- 28753929
TI  - Whole Grain Intake and Glycaemic Control in Healthy Subjects: A Systematic Review
      and Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUNDS: There is growing evidence from both observational and intervention
      studies that Whole Grain (WG) cereals exert beneficial effects on human health,
      especially on the metabolic profile. The aim of this study was to perform a meta
      analysis of randomised controlled trials (RCT) to assess the acute and
      medium/long-term effect of WG foods on glycaemic control and insulin sensitivity
      in healthy individuals. METHODS: A search for all the published RCT on the effect
      of WG food intake on glycaemic and insulin response was performed up to December
      2016. Effect size consisted of mean difference (MD) and 95% CI between the
      outcomes of intervention and the control groups using the generic inverse
      variance random effects model. RESULTS: The meta-analysis of the 14 studies
      testing the acute effects of WG foods showed significant reductions of the post
      prandial values of the glucose iAUC (0-120 min) by -29.71 mmol min/L (95% CI: 
      43.57, -15.85 mmol min/L), the insulin iAUC (0-120 min) by -2.01 nmol min/L (95%
      CI: -2.88, -1.14 nmol min/L), and the maximal glucose and insulin response. In 16
      medium- and long-term RCTs, effects of WG foods on fasting glucose and insulin
      and homeostatic model assessment-insulin resistance values were not significant.
      CONCLUSIONS: The consumption of WG foods is able to improve acutely the
      postprandial glucose and insulin homeostasis compared to similar refined foods in
      healthy subjects. Further research is needed to better understand the long-term
      effects and the biological mechanisms.

PMID- 28753930
TI  - Pregnancy, Proteinuria, Plant-Based Supplemented Diets and Focal Segmental
      Glomerulosclerosis: A Report on Three Cases and Critical Appraisal of the
      Literature.
AB  - Chronic kidney disease (CKD) is increasingly recognized in pregnant patients.
      Three characteristics are associated with a risk of preterm delivery or small for
      gestational age babies; kidney function reduction, hypertension, and proteinuria.
      In pregnancy, the anti-proteinuric agents (ACE-angiotensin converting enzyme
      inhibitors or ARBS -angiotensin receptor blockers) have to be discontinued for
      their potential teratogenicity, and there is no validated approach to control
      proteinuria. Furthermore, proteinuria usually increases as an effect of
      therapeutic changes and pregnancy-induced hyperfiltration. Based on a favourable
      effect of low-protein diets on proteinuria and advanced CKD, our group developed
      a moderately protein-restricted vegan-vegetarian diet tsupplemented with
      ketoacids and aminoacids for pregnant patients. This report describes the results
      obtained in three pregnant patients with normal renal function, nephrotic or sub
      nephrotic proteinuria, and biopsy proven diagnosis of focal segmental
      glomerulosclerosis, a renal lesion in which hyperfiltration is considered of
      pivotal importance (case 1: GFR (glomerular filtration rate): 103 mL/min;
      proteinuria 2.1 g/day; albumin 3.2 g/dL; case 2: GFR 86 mL/min, proteinuria 3.03
      g/day, albumin 3.4 g/dL; case 3: GFR 142 mL/min, proteinuria 6.3 g/day, albumin
      3.23 g/dL). The moderately restricted diet allowed a stabilisation of proteinuria
      in two cases and a decrease in one. No significant changes in serum creatinine
      and serum albumin were observed. The three babies were born at term (38 weeks + 3
      days, female, weight 3180 g-62th centile; 38 weeks + 2 days, female, weight 3300
      g-75th centile; male, 38 weeks + 1 day; 2770 g-8th centile), thus reassuring us
      of the safety of the diet. In summary, based on these three cases studies and a
      review of the literature, we suggest that a moderately protein-restricted,
      supplemented, plant-based diet might contribute to controlling proteinuria in
      pregnant CKD women with focal segmental glomerulosclerosis. However further
      studies are warranted to confirm the potential value of such a treatment
      strategy.

PMID- 28753931
TI  - Preparation of Carriers Based on ZnO Nanoparticles Decorated on Graphene Oxide
      (GO) Nanosheets for Efficient Immobilization of Lipase from Candida rugosa.
AB  - Herein, a promising carrier, graphene oxide (GO) decorated with ZnO
      nanoparticles, denoted as GO/ZnO composite, has been designed and constructed.
      This carrier was characterized by X-ray powder diffraction, scanning electron
      microscopy, Fourier transform infrared spectroscopy and thermogravimetry. Then,
      Candida rugosa lipase (CRL) was immobilized onto the GO-based materials via
      physical adsorption. Our results indicated that the lipase loading amount on the
      GO/ZnO composites was about 73.52 mg of protein per g. In the activity assay, the
      novel immobilized lipase GO/ZnO@CRL, exhibited particularly excellent performance
      in terms of thermostability and reusability. Within 30 min at 50  degrees C, the
      free lipase, GO@CRL and ZnO@CRL had respectively lost 64%, 62% and 41% of their
      initial activity. However, GO/ZnO@CRL still retained its activity of 63% after
      180 min at 50  degrees C. After reuse of the GO/ZnO@CRL 14 times, 90% of the
      initial activity can be recovered. Meanwhile, the relative activity of GO@CRL and
      ZnO@CRL was 28% and 23% under uniform conditions. Hence, GO-decorated ZnO
      nanoparticles may possess great potential as carriers for immobilizing lipase in
      a wide range of applications.

PMID- 28753932
TI  - Effect of Red Ginseng on Genotoxicity and Health-Related Quality of Life after
      Adjuvant Chemotherapy in Patients with Epithelial Ovarian Cancer: A Randomized,
      Double Blind, Placebo-Controlled Trial.
AB  - We evaluated the effect of red ginseng on toxicity, health-related quality of
      life (HRQL) and survival after adjuvant chemotherapy in patients with epithelial
      ovarian cancer (EOC). A total of 30 patients with EOC were randomly assigned to
      placebo (n = 15) and red ginseng groups (n = 15). All patients took placebo or
      red ginseng (3000 mg/day) for three months. Then, we compared changes of
      genotoxicity, HRQL and survival between the two groups. As a result, red ginseng
      reduced micronuclei yield in comparison with placebo despite no difference of
      binucleated cells index. Although red ginseng increased serum levels of alanine
      aminotransferase and aspartate aminotransferase significantly, they were within
      the normal value. Moreover, there were no differences in adverse events between
      placebo and red ginseng groups. In terms of HRQL, red ginseng was associated with
      improved emotional functioning and decreased symptoms of fatigue, nausea and
      vomiting, and dyspnea, reduced anxiety and interference affecting life and
      improved daytime somnolence. However, there was no effect of red ginseng on
      prognosis of EOC. Conclusively, red ginseng may be safe and effective to reduce
      genotoxicity and improve HRQL despite no benefit of survival in patients with EOC
      who received chemotherapy.

PMID- 28753933
TI  - Deciphering Molecular Mechanisms of Interface Buildup and Stability in Porous
      Si/Eumelanin Hybrids.
AB  - Porous Si/eumelanin hybrids are a novel class of organic-inorganic hybrid
      materials that hold considerable promise for photovoltaic applications. Current
      progress toward device setup is, however, hindered by photocurrent stability
      issues, which require a detailed understanding of the mechanisms underlying the
      buildup and consolidation of the eumelanin-silicon interface. Herein we report an
      integrated experimental and computational study aimed at probing interface
      stability via surface modification and eumelanin manipulation, and at modeling
      the organic-inorganic interface via formation of a 5,6-dihydroxyindole (DHI)
      tetramer and its adhesion to silicon. The results indicated that mild silicon
      oxidation increases photocurrent stability via enhancement of the DHI-surface
      interaction, and that higher oxidation states in DHI oligomers create more
      favorable conditions for the efficient adhesion of growing eumelanin.

PMID- 28753934
TI  - Rapid Estimation of Astaxanthin and the Carotenoid-to-Chlorophyll Ratio in the
      Green Microalga Chromochloris zofingiensis Using Flow Cytometry.
AB  - The green microalga Chromochloris zofingiensis can accumulate significant amounts
      of valuable carotenoids, mainly natural astaxanthin, a product with applications
      in functional food, cosmetics, nutraceuticals, and with potential therapeutic
      value in cardiovascular and neurological diseases. To optimize the production of
      astaxanthin, it is essential to monitor the content of astaxanthin in algal cells
      during cultivation. The widely used HPLC (high-performance liquid chromatography)
      method for quantitative astaxanthin determination is time-consuming and
      laborious. In the present work, we present a method using flow cytometry (FCM)
      for in vivo determination of the astaxanthin content and the carotenoid-to
      chlorophyll ratio (Car/Chl) in mixotrophic C. zofingiensis. The method is based
      on the assessment of fluorescent characteristics of cellular pigments. The mean
      fluorescence intensity (MFI) of living cells was determined by FCM to monitor
      pigment formation based on the correlation between MFI detected in particular
      channels (FL1: 533 +/- 15 nm; FL2: 585 +/- 20 nm; FL3: >670 nm) and pigment
      content in algal cells. Through correlation and regression analysis, a linear
      relationship was observed between MFI in FL2 (band-pass filter, emission at 585
      nm in FCM) and astaxanthin content (in HPLC) and applied for predicting
      astaxanthin content. With similar procedures, the relationships between MFI in
      different channels and Car/Chl ratio in mixotrophic C. zofingiensis were also
      determined. Car/Chl ratios could be estimated by the ratios of MFI (FL1/FL3,
      FL2/FL3). FCM is thus a highly efficient and feasible method for rapid estimation
      of astaxanthin content in the green microalga C. zofingiensis. The rapid FCM
      method is complementary to the current HPLC method, especially for rapid
      evaluation and prediction of astaxanthin formation as it is required during the
      high-throughput culture in the laboratory and mass cultivation in industry.

PMID- 28753935
TI  - Influences of Orally Taken Carotenoid-Rich Curly Kale Extract on Collagen
      I/Elastin Index of the Skin.
AB  - Two differently designed, spatially resolved reflectance spectroscopy-based
      scanners and two-photon tomography were used for noninvasive in vivo
      determination of cutaneous carotenoids, and collagen I/elastin aging index of
      dermis, respectively, in the skin of 29 healthy female volunteers between 40 and
      56 years of age. The volunteers received a supplement in the form of a carotenoid
      rich natural curly kale extract containing 1650 ug of carotenoids in total (three
      capsules of 550 ug), once a day. Measurements were taken before, after 5 months
      and after 10 months of daily supplementation. The results showed significantly
      increased values for the cutaneous carotenoids and the collagen I/elastin aging
      index of dermis 5 and 10 months after the beginning of the study. The obtained
      results show that a natural carotenoid-rich extract could prevent the aging
      related collagen I degradation in the dermis and improve the extracellular
      matrix.

PMID- 28753936
TI  - Structural Insight into the Recognition of r(UAG) by Musashi-1 RBD2, and
      Construction of a Model of Musashi-1 RBD1-2 Bound to the Minimum Target RNA.
AB  - Musashi-1 (Msi1) controls the maintenance of stem cells and tumorigenesis through
      binding to its target mRNAs and subsequent translational regulation. Msi1 has two
      RNA-binding domains (RBDs), RBD1 and RBD2, which recognize r(GUAG) and r(UAG),
      respectively. These minimal recognition sequences are connected by variable
      linkers in the Msi1 target mRNAs, however, the molecular mechanism by which Msi1
      recognizes its targets is not yet understood. We previously determined the
      solution structure of the Msi1 RBD1:r(GUAGU) complex. Here, we determined the
      first structure of the RBD2:r(GUAGU) complex. The structure revealed that the
      central trinucleotide, r(UAG), is specifically recognized by the intermolecular
      hydrogen-bonding and aromatic stacking interactions. Importantly, the C-terminal
      region, which is disordered in the free form, took a certain conformation,
      resembling a helix. The observation of chemical shift perturbation and
      intermolecular NOEs, together with increases in the heteronuclear steady-state
      {1H}-15N NOE values on complex formation, indicated the involvement of the C
      terminal region in RNA binding. On the basis of the two complex structures, we
      built a structural model of consecutive RBDs with r(UAGGUAG) containing both
      minimal recognition sequences, which resulted in no steric hindrance. The model
      suggests recognition of variable lengths (n) of the linker up to n = 50 may be
      possible.

PMID- 28753937
TI  - Microindolinone A, a Novel 4,5,6,7-Tetrahydroindole, from the Deep-Sea-Derived
      Actinomycete Microbacterium sp. MCCC 1A11207.
AB  - A novel indole, microindolinone A (1), was isolated from a deep-sea-derived
      actinomycete Microbacterium sp. MCCC 1A11207, together with 18 known compounds (2
      19). By detailed analysis of the 1H, 13C, HSQC, COSY, HMBC, high resolution
      electron spray ionization mass spectrum (HRESIMS), and circular dichroism (CD)
      data, the absolute configuration of 1 was elucidated as 5R-hydroxy-4,5,6,7
      tetrahydroindole-4-one. It is noteworthy that 1 is the second example of a
      saturated indole isolated from nature.

PMID- 28753938
TI  - 15N-, 13C- and 1H-NMR Spectroscopy Characterization and Growth Inhibitory Potency
      of a Combi-Molecule Synthesized by Acetylation of an Unstable Monoalkyltriazene.
AB  - 6-(3-Methyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione referred to as
      EG22 (8a), is an open-chain 3-alkyl-1,2,3-triazene termed "combi-molecule"
      designed to inhibit poly(adenosine diphosphate ribose) polymerase (PARP) and
      damage DNA. To delay its hydrolysis, acetylation of N3 was required. Being a
      monoalkyl-1,2,3-triazene, EG22 could assume two tautomers in solution or lose
      nitrogen during the reaction, thereby leading to several acetylated compounds.
      Instead, one compound was observed and to unequivocally assign its structure, we
      introduced isotopically labeled reagents in its preparation, with the purpose of
      incorporating 15N at N2 and 13C in the 3-methyl group. The results showed that
      the 1,2,3-triazene moiety remained intact, as confirmed by 15N-NMR, coupling
      patterns between the 15N-labeled N2 and the 13C-labeled methyl group.
      Furthermore, we undertook heteronuclear single quantum coherence (HSQC) and
      heteronuclear multiple bond correlation (HMBC) experiments that permitted the
      detection and assignment of all four nitrogens in 6-(3-acetyl-3-methyltriaz-1-en
      1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione, referred to as ZSM02 (9a), whose
      structure was further confirmed by X-ray crystallography. The structure showed a
      remarkable coplanarity between the N-acetyltriazene and the naphtalimide moiety.
      Thus, we unequivocally assigned 9a as the product of the reaction and compared
      its growth inhibitory activity with that of its precursor, EG22. ZSM02 exhibited
      identical growth inhibitory profile as EG22, suggesting that it may be a prodrug
      of EG22.

PMID- 28753939
TI  - Using Iron-Manganese Co-Oxide Filter Film to Remove Ammonium from Surface Water.
AB  - An iron-manganese co-oxide filter film (MeOx) has been proven to be a good
      catalyst for the chemical catalytic oxidation of ammonium in groundwater.
      Compared with groundwater, surface water is generally used more widely and has
      characteristics that make ammonium removal more difficult. In this study, MeOx
      was used to remove ammonium from surface water. It indicated that the average
      ammonium removal efficiency of MeOx was greater than 90%, even though the water
      quality changed dramatically and the water temperature was reduced to about 6-8 
      degrees C. Then, through inactivating microorganisms, it showed that the removal
      capability of MeOx included both biological (accounted for about 41.05%) and
      chemical catalytic oxidation and chemical catalytic oxidation (accounted for
      about 58.95%). The investigation of the characterizations suggested that MeOx was
      formed by abiotic ways and the main elements on the surface of MeOx were
      distributed homogenously. The analysis of the catalytic oxidation process
      indicated that ammonia nitrogen may interact with MeOx as both ammonia molecules
      and ammonium ions and the active species of O2 were possibly *O and O2-.

PMID- 28753940
TI  - Coping with Fear of and Exposure to Terrorism among Expatriates.
AB  - This paper examines existing research on the impact of terrorism on expatriate
      coping strategies. We consider pre-assignment fear of terrorism, in-country
      coping strategies, and anxiety and posttraumatic stress disorder (PTSD)
      associated with repatriation. The extant research is small but growing. Our model
      for expatriate coping at the pre-departure, in-country, and repatriation stages
      includes strategies specific to each stage. Preparation using proactive coping,
      systematic desensitization, problem and emotion focused coping, social support,
      and virtual reality explorations are recommended. Selecting expatriate candidates
      who are well-adjusted, emotionally intelligent, and possessing good coping skills
      is essential for successful assignments in terror-prone regions.

PMID- 28753941
TI  - Proteostasis of Huntingtin in Health and Disease.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by
      motor dysfunction, cognitive deficits and psychosis. HD is caused by mutations in
      the Huntingtin (HTT) gene, resulting in the expansion of polyglutamine (polyQ)
      repeats in the HTT protein. Mutant HTT is prone to aggregation, and the
      accumulation of polyQ-expanded fibrils as well as intermediate oligomers formed
      during the aggregation process contribute to neurodegeneration. Distinct protein
      homeostasis (proteostasis) nodes such as chaperone-mediated folding and
      proteolytic systems regulate the aggregation and degradation of HTT. Moreover,
      polyQ-expanded HTT fibrils and oligomers can lead to a global collapse in
      neuronal proteostasis, a process that contributes to neurodegeneration. The
      ability to maintain proteostasis of HTT declines during the aging process.
      Conversely, mechanisms that preserve proteostasis delay the onset of HD. Here we
      will review the link between proteostasis, aging and HD-related changes.

PMID- 28753942
TI  - Quercetin and Green Tea Extract Supplementation Downregulates Genes Related to
      Tissue Inflammatory Responses to a 12-Week High Fat-Diet in Mice.
AB  - Quercetin (Q) and green tea extract (E) are reported to counter insulin
      resistance and inflammation and favorably alter fat metabolism. We investigated
      whether a mixture of E + Q (EQ) could synergistically influence metabolic and
      inflammation endpoints in a high-fat diet (HFD) fed to mice. Male C57BL/6 mice (n
      = 40) were put on HFD (fat = 60%kcal) for 12 weeks and randomly assigned to Q (25
      mg/kg of body weight (BW)/day), E (3 mg of epigallocatechin gallate/kg BW/day),
      EQ, or control groups for four weeks. At 16 weeks, insulin sensitivity was
      measured via the glucose tolerance test (GTT), followed by area-under-the-curve
      (AUC) estimations. Plasma cytokines and quercetin were also measured, along with
      whole genome transcriptome analysis and real-time polymerase chain reaction
      (qPCR) on adipose, liver, and skeletal muscle tissues. Univariate analyses were
      conducted via analysis of variance (ANOVA), and whole-genome expression profiles
      were examined via gene set enrichment. At 16 weeks, plasma quercetin levels were
      higher in Q and EQ groups vs. the control and E groups (p < 0.05). Plasma
      cytokines were similar among groups (p > 0.05). AUC estimations for GTT was 14%
      lower for Q vs. E (p = 0.0311), but non-significant from control (p = 0.0809).
      Genes for cholesterol metabolism and immune and inflammatory response were
      downregulated in Q and EQ groups vs. control in adipose tissue and soleus muscle
      tissue. These data support an anti-inflammatory role for Q and EQ, a result best
      captured when measured with tissue gene downregulation in comparison to changes
      in plasma cytokine levels.

PMID- 28753943
TI  - Reduced Stress and Improved Sleep Quality Caused by Green Tea Are Associated with
      a Reduced Caffeine Content.
AB  - Caffeine, one of the main components in green tea, can interfere with sleep and
      block the effect of theanine. Since theanine, the main amino acid in tea leaves,
      has significant anti-stress effects in animals and humans, we examined the
      effects of green tea with lowered caffeine content, i.e., low-caffeine green tea
      (LCGT), on stress and quality of sleep of middle-aged individuals (n = 20, mean
      age 51.3 +/- 6.7 years) in a double-blind crossover design. Standard green tea
      (SGT) was used as the control. These teas (>=300 mL/day), which were eluted with
      room temperature water, were consumed over a period of seven days after a single
      washout term. The level of salivary alpha-amylase activity (sAA), a stress
      marker, was significantly lower in participants that consumed LCGT (64.7 U/mL)
      than in those that consumed SGT (73.9 U/mL). Sleep quality was higher in
      participants that consumed a larger quantity of LCGT. In addition, a self
      diagnostic check for accumulated fatigue was significantly lower in those
      participants that consumed LCGT than SGT. These results indicate that LCGT intake
      can reduce stress in middle-aged individuals and improve their quality of sleep.
      The reduction in caffeine is suggested to be a valid reason for enhancing the
      anti-stress effect of green tea.

PMID- 28753944
TI  - Association between Visual Impairment and Low Vision and Sleep Duration and
      Quality among Older Adults in South Africa.
AB  - This study aims to estimate the association between visual impairment and low
      vision and sleep duration and poor sleep quality in a national sample of older
      adults in South Africa. A national population-based cross-sectional Study of
      Global Ageing and Adults Health (SAGE) wave 1 was conducted in 2008 with a sample
      of 3840 individuals aged 50 years or older in South Africa. The interviewer
      administered questionnaire assessed socio-demographic characteristics, health
      variables, sleep duration, quality, visual impairment, and vision. Results
      indicate that 10.0% of the sample reported short sleep duration (<=5 h), 46.6%
      long sleep (>=9 h), 9.3% poor sleep quality, 8.4% self-reported and visual
      impairment (near and/or far vision); and 43.2% measured low vision (near and/or
      far vision) (0.01-0.25 decimal) and 7.5% low vision (0.01-0.125 decimal). In
      fully adjusted logistic regression models, self-reported visual impairment was
      associated with short sleep duration and poor sleep quality, separately and
      together. Low vision was only associated with long sleep duration and poor sleep
      quality in unadjusted models. Self-reported visual impairment was related to both
      short sleep duration and poor sleep quality. Population data on sleep patterns
      may want to include visual impairment measures.

PMID- 28753945
TI  - Developing and Validating an Age-Independent Equation Using Multi-Frequency
      Bioelectrical Impedance Analysis for Estimation of Appendicular Skeletal Muscle
      Mass and Establishing a Cutoff for Sarcopenia.
AB  - Background: Appendicular skeletal muscle (or lean) mass (ALM) estimated using
      dual-energy X-ray absorptiometry (DXA) is considered to be a preferred method for
      sarcopenia studies. However, DXA is expensive, has limited portability, and
      requires radiation exposure. Bioelectrical impedance analysis (BIA) is
      inexpensive, easy to use, and portable; thus BIA might be useful in sarcopenia
      investigations. However, a large variety of models have been commercially
      supplied by different companies, and for most consumer products, the equations
      estimating ALM are not disclosed. It is therefore difficult to use these
      equations for research purposes. In particular, the BIA equation is often age
      dependent, which leads to fundamental difficulty in examining age-related ALM
      loss. The aims of the current study were as follows: (1) to develop and validate
      an equation to estimate ALM using multi-frequency BIA (MF-BIA) based on
      theoretical models, and (2) to establish sarcopenia cutoff values using the
      equation for the Japanese population. Methods: We measured height (Ht), weight,
      and ALM obtained using DXA and a standing-posture 8-electrode MF-BIA (5, 50, 250
      kHz) in 756 Japanese individuals aged 18 to 86-years-old (222 men and 301 women
      as developing equation group and 97 men and 136 women as a cross validation
      group). The traditional impedance index (Ht2/Z50) and impedance ratio of high and
      low frequency (Z250/Z5) of hand to foot values were calculated. Multiple
      regression analyses were conducted with ALM as dependent variable in men and
      women separately. Results: We created the following equations: ALM = (0.6947 *
      (Ht2/Z50)) + (-55.24 * (Z250/Z5)) + (-10,940 * (1/Z50)) + 51.33 for men, and ALM
      = (0.6144 * (Ht2/Z50)) + (-36.61 * (Z250/Z5)) + (-9332 * (1/Z50)) + 37.91 for
      women. Additionally, we conducted measurements in 1624 men and 1368 women aged 18
      to 40 years to establish sarcopenia cutoff values in the Japanese population. The
      mean values minus 2 standard deviations of the skeletal muscle mass index
      (ALM/Ht2) in these participants were 6.8 and 5.7 kg/m2 in men and women,
      respectively. Conclusion: The current study established and validated a
      theoretical and age-independent equation using MF-BIA to estimate ALM and
      provided reasonable sarcopenia cutoff values.

PMID- 28753946
TI  - Molecular Weights of Bovine and Porcine Heparin Samples: Comparison of
      Chromatographic Methods and Results of a Collaborative Survey.
AB  - In a collaborative study involving six laboratories in the USA, Europe, and India
      the molecular weight distributions of a panel of heparin sodium samples were
      determined, in order to compare heparin sodium of bovine intestinal origin with
      that of bovine lung and porcine intestinal origin. Porcine samples met the
      current criteria as laid out in the USP Heparin Sodium monograph. Bovine lung
      heparin samples had consistently lower average molecular weights. Bovine
      intestinal heparin was variable in molecular weight; some samples fell below the
      USP limits, some fell within these limits and others fell above the upper limits.
      These data will inform the establishment of pharmacopeial acceptance criteria for
      heparin sodium derived from bovine intestinal mucosa. The method for MW
      determination as described in the USP monograph uses a single, broad standard
      calibrant to characterize the chromatographic profile of heparin sodium on high
      resolution silica-based GPC columns. These columns may be short-lived in some
      laboratories. Using the panel of samples described above, methods based on the
      use of robust polymer-based columns have been developed. In addition to the use
      of the USP's broad standard calibrant for heparin sodium with these columns, a
      set of conditions have been devised that allow light-scattering detected
      molecular weight characterization of heparin sodium, giving results that agree
      well with the monograph method. These findings may facilitate the validation of
      variant chromatographic methods with some practical advantages over the USP
      monograph method.

PMID- 28753947
TI  - Thermal Anemometry Grid Sensor.
AB  - A novel thermal anemometry grid sensor was developed for the simultaneous
      measurement of cross-sectional temperature and axial velocity distribution in a
      fluid flow. The sensor consists of a set of platinum resistors arranged in a
      regular grid. Each platinum resistor allows the simultaneous measurement of fluid
      temperature via electrical resistance and flow velocity via constant voltage
      thermal anemometry. Cross-sectional measurement was enabled by applying a special
      multiplexing-excitation scheme. In this paper, we present the design and
      characterization of a prototypical sensor for measurements in a range of very low
      velocities.

PMID- 28753948
TI  - Selective Detection of Target Volatile Organic Compounds in Contaminated Humid
      Air Using a Sensor Array with Principal Component Analysis.
AB  - We investigated selective detection of the target volatile organic compounds
      (VOCs) nonanal, n-decane, and acetoin for lung cancer-related VOCs, and acetone
      and methyl i-butyl ketone for diabetes-related VOCs, in humid air with simulated
      VOC contamination (total concentration: 300 MUg/m3). We used six "grain boundary
      response type" sensors, including four commercially available sensors (TGS 2600,
      2610, 2610, and 2620) and two Pt, Pd, and Au-loaded SnO2 sensors (Pt, Pd,
      Au/SnO2), and two "bulk-response type" sensors, including Zr-doped CeO2 (CeZr10),
      i.e., eight sensors in total. We then analyzed their sensor signals using
      principal component analysis (PCA). Although the six "grain boundary-response
      type" sensors were found to be insufficient for selective detection of the target
      gases in humid air, the addition of two "bulk-response type" sensors improved the
      selectivity, even with simulated VOC contamination. To further improve the
      discrimination, we selected appropriate sensors from the eight sensors based on
      the PCA results. The selectivity to each target gas was maintained and was not
      affected by contamination.

PMID- 28753949
TI  - Radial Distance Estimation with Tapered Whisker Sensors.
AB  - Rats use their whiskers as tactile sensors to sense their environment. Active
      whisking, moving whiskers back and forth continuously, is one of prominent
      features observed in rodents. They can discriminate different textures or extract
      features of a nearby object such as size, shape and distance through active
      whisking. There have been studies to localize objects with artificial whiskers
      inspired by rat whiskers. The linear whisker model based on beam theory has been
      used to estimate the radial distance, that is, the distance between the base of
      the whisker and a target object. In this paper, we investigate deflection angle
      measurements instead of forces or moments, based on a linear tapered whisker
      model to see the role of tapered whiskers found in real animals. We analyze how
      accurately this model estimates the radial distance, and quantify the estimation
      errors and noise sensitivity. We also compare the linear model simulation and
      nonlinear numerical solutions. It is shown that the radial distance can be
      estimated using deflection angles at two different positions on the tapered
      whisker. We argue that the tapered whisker has an advantage of estimating the
      radial distance better, as compared to an untapered whisker, and active sensing
      allows that estimation without the whisker's material property and thickness or
      the moment at base. In addition, we investigate the potential of passive sensing
      for tactile localization.

PMID- 28753950
TI  - Perturbation of Human T-Cell Leukemia Virus Type 1 Particle Morphology by
      Differential Gag Co-Packaging.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is an important cancer-causing human
      retrovirus that has infected approximately 15 million individuals worldwide. Many
      aspects of HTLV-1 replication, including virus particle structure and assembly,
      are poorly understood. Group-specific antigen (Gag) proteins labeled at the
      carboxy terminus with a fluorophore protein have been used extensively as a
      surrogate for fluorescence studies of retroviral assembly. How these tags affect
      Gag stoichiometry and particle morphology has not been reported in detail. In
      this study, we used an HTLV-1 Gag expression construct with the yellow
      fluorescence protein (YFP) fused to the carboxy-terminus as a surrogate for the
      HTLV-1 Gag-Pol to assess the effects of co-packaging of Gag and a Gag-YFP on
      virus-like particle (VLP) morphology and analyzed particles by cryogenic
      transmission electron microscopy (cryo-TEM). Scanning transmission electron
      microscopy (STEM) and fluorescence fluctuation spectroscopy (FFS) were also used
      to determine the Gag stoichiometry. We found that ratios of 3:1 (Gag:Gag-YFP) or
      greater resulted in a particle morphology indistinguishable from that of VLPs
      produced with the untagged HTLV-1 Gag, i.e., a mean diameter of ~113 nm and a
      mass of 220 MDa as determined by cryo-TEM and STEM, respectively. Furthermore,
      FFS analysis indicated that HTLV-1 Gag-YFP was incorporated into VLPs in a
      predictable manner at the 3:1 Gag:Gag-YFP ratio. Both STEM and FFS analyses found
      that the Gag copy number in VLPs produced with a 3:1 ratio of Gag:Gag-YFP was is
      in the range of 1500-2000 molecules per VLP. The observations made in this study
      indicate that biologically relevant Gag-Gag interactions occur between Gag and
      Gag-YFP at ratios of 3:1 or higher and create a Gag lattice structure in VLPs
      that is morphologically indistinguishable from that of VLPs produced with just
      untagged Gag. This information is useful for the quantitative analysis of Gag-Gag
      interactions that occur during virus particle assembly and in released immature
      particles.

PMID- 28753951
TI  - A Q-Learning-Based Delay-Aware Routing Algorithm to Extend the Lifetime of
      Underwater Sensor Networks.
AB  - Underwater sensor networks (UWSNs) have become a hot research topic because of
      their various aquatic applications. As the underwater sensor nodes are powered by
      built-in batteries which are difficult to replace, extending the network lifetime
      is a most urgent need. Due to the low and variable transmission speed of sound,
      the design of reliable routing algorithms for UWSNs is challenging. In this
      paper, we propose a Q-learning based delay-aware routing (QDAR) algorithm to
      extend the lifetime of underwater sensor networks. In QDAR, a data collection
      phase is designed to adapt to the dynamic environment. With the application of
      the Q-learning technique, QDAR can determine a global optimal next hop rather
      than a greedy one. We define an action-utility function in which residual energy
      and propagation delay are both considered for adequate routing decisions. Thus,
      the QDAR algorithm can extend the network lifetime by uniformly distributing the
      residual energy and provide lower end-to-end delay. The simulation results show
      that our protocol can yield nearly the same network lifetime, and can reduce the
      end-to-end delay by 20-25% compared with a classic lifetime-extended routing
      protocol (QELAR).

PMID- 28753952
TI  - Amperometric Microsensors Monitoring Glutamate-Evoked In Situ Responses of Nitric
      Oxide and Carbon Monoxide from Live Human Neuroblastoma Cells.
AB  - In the brain, nitric oxide (NO) and carbon monoxide (CO) are important signaling
      gases which have multifaceted roles, such as neurotransmitters, neuromodulators,
      and vasodilators. Even though it is difficult to measure NO and CO in a living
      system due to their high diffusibility and extremely low release levels,
      electrochemical sensors are promising tools to measure in vivo and in vitro NO
      and CO gases. In this paper, using amperometric dual and septuple NO/CO
      microsensors, real-time NO and CO changes evoked by glutamate were monitored
      simultaneously for human neuroblastoma (SH-SY5Y) cells. In cultures, the cells
      were differentiated and matured into functional neurons by retinoic acid and
      brain-derived neurotrophic factor. When glutamate was administrated to the cells,
      both NO and CO increases and subsequent decreases returning to the basal levels
      were observed with a dual NO/CO microsensor. In order to facilitate sensor's
      measurement, a flower-type septuple NO/CO microsensor was newly developed and
      confirmed in terms of the sensitivity and selectivity. The septuple microsensor
      was employed for the measurements of NO and CO changes as a function of distances
      from the position of glutamate injection. Our sensor measurements revealed that
      only functionally differentiated cells responded to glutamate and released NO and
      CO.

PMID- 28753953
TI  - Unravelling the Role of Metallothionein on Development, Reproduction and
      Detoxification in the Wall Lizard Podarcis sicula.
AB  - Metallothioneins (MTs) are an evolutionary conserved multigene family of proteins
      whose role was initially identified in binding essential metals. The
      physiological role of MT, however, has been revealed to be more complex than
      expected, since not only are MTs able to bind to toxic heavy metals, but many
      isoforms have shown specialized and alternative functions. Within this
      uncertainty, the information available on MTs in non-mammalian vertebrates,
      particularly in neglected tetrapods such as the reptiles, is even more scant. In
      this review, we provide a summary of the current understanding on metallothionein
      presence and function in the oviparous lizard Podarcis sicula, highlighting the
      results obtained by studying MT gene expression in most representative adult and
      embryonic tissues. The results demonstrate that in adults, cadmium induces MT
      transcription in a dose- and tissue-specific manner. Thus, the MT mRNAs appear,
      at least in some cases, to be an unsuitable tool for detecting environmental ion
      contamination. In early embryos, maternal RNAs sustain developmental needs for MT
      protein until organogenesis is well on its way. At this time, transcription
      starts, but again in a tissue- and organ-specific manner, suggesting an
      involvement in alternative roles. In conclusion, the spatiotemporal distribution
      of transcripts in adults and embryos definitively confirms that MT has deserved
      the title of elusive protein.

PMID- 28753954
TI  - Isoegomaketone Alleviates the Development of Collagen Antibody-Induced Arthritis
      in Male Balb/c Mice.
AB  - In this study, we attempted to identify and assess effects of isoegomaketone (IK)
      isolated from Perilla frutescens var. crispa on the development of rheumatoid
      arthritis (RA). RA was induced in male Balb/c mice by collagen antibody
      injection. Experimental animals were randomly divided into five groups: normal,
      collagen antibody-induced arthritis (CAIA), CAIA + IK (5 mg/kg/day), CAIA + IK
      (10 mg/kg/day), and CAIA + apigenin (16 mg/kg/day) and respective treatments were
      administered via oral gavage once per day for four days. Mice treated with IK (10
      mg/kg/day) developed less severe arthritis than the control CAIA mice. Arthritic
      score, paw volume, and paw thickness were less significant compared to the
      control CAIA mice at day seven (73%, 15%, and 14% lower, respectively).
      Furthermore, histopathological examination of ankle for inflammation showed that
      infiltration of inflammatory cells and edema formation were reduced by IK
      treatment. Similarly, neutrophil to lymphocyte ratio (NLR) in whole blood was
      lower in mice treated with IK (10 mg/kg/day) by 85% when compared to CAIA mice.
      Taken together, treatment with IK delays the onset of the arthritis and
      alleviates the manifestations of arthritis in CAIA mice.

PMID- 28753955
TI  - Investigation into the Effect of Acoustic Radiation Force and Acoustic Streaming
      on Particle Patterning in Acoustic Standing Wave Fields.
AB  - Acoustic standing waves have been widely used in trapping, patterning, and
      manipulating particles, whereas one barrier remains: the lack of understanding of
      force conditions on particles which mainly include acoustic radiation force (ARF)
      and acoustic streaming (AS). In this paper, force conditions on micrometer size
      polystyrene microspheres in acoustic standing wave fields were investigated. The
      COMSOL(r) Mutiphysics particle tracing module was used to numerically simulate
      force conditions on various particles as a function of time. The velocity of
      particle movement was experimentally measured using particle imaging velocimetry
      (PIV). Through experimental and numerical simulation, the functions of ARF and AS
      in trapping and patterning were analyzed. It is shown that ARF is dominant in
      trapping and patterning large particles while the impact of AS increases rapidly
      with decreasing particle size. The combination of using both ARF and AS for
      medium size particles can obtain different patterns with only using ARF. Findings
      of the present study will aid the design of acoustic-driven microfluidic devices
      to increase the diversity of particle patterning.

PMID- 28753956
TI  - Predicting Magnetoelectric Coupling in Layered and Graded Composites.
AB  - Magnetoelectric (ME) interaction in magnetostrictive-piezoelectric multiferroic
      structures consists in inducing the electric field across the structure in an
      applied magnetic field and is a product property of magnetostriction and
      piezoelectricity in components. ME voltage coefficient that is the ratio of
      induced electric field to applied magnetic field is the key parameter of ME
      coupling strength. It has been known that the ME coupling strength is dictated by
      the product of the piezoelectric and piezomagnetic coefficients of initial
      phases. As a result, using the laminates with graded piezoelectric and
      piezomagnetic parameters are a new pathway to the increase in the ME coupling
      strength. Recently developed models predict stronger ME interactions in
      composites based on graded components compared to homogeneous ones. We discuss
      predicting the ME coupling strength for layered structures of homogeneous and
      compositionally graded magnetostrictive and piezoelectric components based on the
      graphs of ME voltage coefficients against composite parameters. For obtaining the
      graphs, we developed equations for ME output in applied magnetic field for
      possible modes of operation and layered structure configurations. In particular,
      our studies have been performed on low-frequency ME coupling, enhanced ME effect
      in electromechanical resonance (EMR) region for longitudinal and bending modes.
      Additionally, ME coupling at magnetic resonance in magnetostrictive component and
      at overlapping the EMR and magnetic resonance is investigated. We considered
      symmetric trilayers and asymmetric bilayers of magnetostrictive and piezoelectric
      components and multilayered structures based on compositionally stepped initial
      components.

PMID- 28753957
TI  - The Uremic Toxin Indoxyl Sulfate Accelerates Thrombotic Response after Vascular
      Injury in Animal Models.
AB  - Chronic kidney disease (CKD) patients are at high risk for thrombotic events.
      Indoxyl sulfate (IS) is one of the most potent uremic toxins that accumulates
      during CKD. Even though IS is associated with an increased risk for
      cardiovascular disease, its impact on thrombotic events still remains not fully
      understood. The purpose of the study was to evaluate the direct effect of IS on
      thrombotic process. We examined the impact of acute exposure to IS on thrombus
      development induced by electric current in Wistar rats, intravital thrombus
      formation after laser-induced injury in the mice endothelium, coagulation
      profile, clot formation dynamics, platelet aggregations, and erythrocyte osmotic
      resistance. IS doses: 10, 30 and 100 mg/kg body weight (b.w.) increased weight of
      thrombus induced by electric current in dose-dependent manner (p < 0.001).
      Furthermore, two highest IS doses increased laser-induced thrombus formation
      observed via confocal system (increase in fluorescence intensity and total
      thrombus area (p < 0.01)). Only the highest IS dose decreased clotting time (p <
      0.01) and increased maximum clot firmness (p < 0.05). IS did not affect blood
      morphology parameters and erythrocyte osmotic resistance, but augmented collagen
      induced aggregation. Obtained data indicate that IS creates prothrombotic state
      and contributes to more stable thrombus formation. Thus, we concluded that IS may
      be one of crucial uremic factors promoting thrombotic events in CKD patients.

PMID- 28753958
TI  - Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan
      Infants.
AB  - Iron supplementation may have adverse health effects in infants, probably through
      manipulation of the gut microbiome. Previous research in low-resource settings
      have focused primarily on anemic infants. This was a double blind, randomized,
      controlled trial of home fortification comparing multiple micronutrient powder
      (MNP) with and without iron. Six-month-old, non- or mildly anemic, predominantly
      breastfed Kenyan infants in a rural malaria-endemic area were randomized to
      consume: (1) MNP containing 12.5 mg iron (MNP+Fe, n = 13); (2) MNP containing no
      iron (MNP-Fe, n = 13); or (3) Placebo (CONTROL, n = 7), from 6-9 months of age.
      Fecal microbiota were profiled by high-throughput bacterial 16S rRNA gene
      sequencing. Markers of inflammation in serum and stool samples were also
      measured. At baseline, the most abundant phylum was Proteobacteria (37.6% of rRNA
      sequences). The proteobacterial genus Escherichia was the most abundant genus
      across all phyla (30.1% of sequences). At the end of the intervention, the
      relative abundance of Escherichia significantly decreased in MNP-Fe (-16.05 +/-
      6.9%, p = 0.05) and CONTROL (-19.75 +/- 4.5%, p = 0.01), but not in the MNP+Fe
      group (-6.23 +/- 9%, p = 0.41). The second most abundant genus at baseline was
      Bifidobacterium (17.3%), the relative abundance of which significantly decreased
      in MNP+Fe (-6.38 +/- 2.5%, p = 0.02) and CONTROL (-8.05 +/- 1.46%, p = 0.01), but
      not in MNP-Fe (-4.27 +/- 5%, p = 0.4445). Clostridium increased in MNP-Fe only
      (1.9 +/- 0.5%, p = 0.02). No significant differences were observed in
      inflammation markers, except for IL-8, which decreased in CONTROL. MNP
      fortification over three months in non- or mildly anemic Kenyan infants can
      potentially alter the gut microbiome. Consistent with previous research, addition
      of iron to the MNP may adversely affect the colonization of potential beneficial
      microbes and attenuate the decrease of potential pathogens.

PMID- 28753959
TI  - New Insights into the Role of Autophagy in Tumor Immune Microenvironment.
AB  - The tumor microenvironment is a complex system that is affected by various
      factors, including hypoxia, acidosis, and immune and inflammatory responses,
      which have significant effects on tumor adhesion, invasion, metastasis,
      angiogenesis, and autophagy. In this hostile tumor microenvironment, autophagy of
      tumor cells can promote tumor growth and metastasis. As autophagy is a double
      edged sword in tumors, treatment of cancer via regulation of autophagy is
      extremely complicated. Therefore, understanding the relationship between tumor
      autophagy and the tumor microenvironment is extremely important. As the immune
      milieu plays an important role in tumor development, immunotherapy has become a
      promising form of cancer therapy. A multi-pronged treatment approach using
      immunotherapy and molecular targets may become the major direction for future
      cancer treatments. This article reviews existing knowledge regarding the immune
      factors in the tumor microenvironment and the status of tumor autophagy research.

PMID- 28753960
TI  - Anti-Inflammatory Triterpene Glycosides from the Roots of Ilex dunniana Levl.
AB  - A new triterpene glycoside ilexdunnoside A (1) and a new sulfated triterpene
      derivative ilexdunnoside B (2), together with five known analogues 3-7 were
      isolated from the roots of Ilex dunniana Levl. The structures were established by
      NMR spectroscopic analysis and acid hydrolysis. Results of an in vivo study of
      the biological activity showed that 75% ethanol and n-butanol extracts of the
      plant displayed anti-inflammatory activities against ear edema in mice, with
      inhibition rates of 23.5% and 37.5%, respectively, at a dose of 50 mg/kg.
      Furthermore, Compounds 1, 2 and 3 exhibited moderate indirect inhibitory effects
      on lipopolysaccharide-induced NO production in BV2 microglial cells in vitro,
      with IC50 values of 11.60, 12.30 and 9.70 MUM, respectively.

PMID- 28753961
TI  - Lateral Violence in Nursing Survey: Instrument Development and Validation.
AB  - An examination of the psychometric properties of the Lateral Violence in Nursing
      Survey (LVNS), an instrument previously developed to measure the perceived
      incidence and severity of lateral violence (LV) in the nursing workplace, was
      carried out. Conceptual clustering and principal components analysis were used
      with survey responses from 663 registered nurses and ancillary nursing staff in a
      southeastern tertiary care medical center. Where appropriate, Cronbach's alpha
      (alpha) evaluated internal consistency. The prevalence/severity of lateral
      violence items constitute two distinct subscales (LV by self and others) with
      Cronbach's alpha of 0.74 and 0.86, respectively. The items asking about potential
      causes of LV are unidimensional and internally consistent (alpha = 0.77) but
      there is no conceptually coherent theme underlying the various causes.
      Respondents rating a potential LV cause as "major" scored higher on both
      prevalence/severity subscales than those rating it a "minor" cause or not a
      cause. Subsets of items on the LVNS are internally reliable, supporting construct
      validity. Revisions of the original LVNS instrument will improve its use in
      future work.

PMID- 28753962
TI  - Dynamic Hierarchical Energy-Efficient Method Based on Combinatorial Optimization
      for Wireless Sensor Networks.
AB  - Routing protocols based on topology control are significantly important for
      improving network longevity in wireless sensor networks (WSNs). Traditionally,
      some WSN routing protocols distribute uneven network traffic load to sensor
      nodes, which is not optimal for improving network longevity. Differently to
      conventional WSN routing protocols, we propose a dynamic hierarchical protocol
      based on combinatorial optimization (DHCO) to balance energy consumption of
      sensor nodes and to improve WSN longevity. For each sensor node, the DHCO
      algorithm obtains the optimal route by establishing a feasible routing set
      instead of selecting the cluster head or the next hop node. The process of
      obtaining the optimal route can be formulated as a combinatorial optimization
      problem. Specifically, the DHCO algorithm is carried out by the following
      procedures. It employs a hierarchy-based connection mechanism to construct a
      hierarchical network structure in which each sensor node is assigned to a special
      hierarchical subset; it utilizes the combinatorial optimization theory to
      establish the feasible routing set for each sensor node, and takes advantage of
      the maximum-minimum criterion to obtain their optimal routes to the base station.
      Various results of simulation experiments show effectiveness and superiority of
      the DHCO algorithm in comparison with state-of-the-art WSN routing algorithms,
      including low-energy adaptive clustering hierarchy (LEACH), hybrid energy
      efficient distributed clustering (HEED), genetic protocol-based self-organizing
      network clustering (GASONeC), and double cost function-based routing (DCFR)
      algorithms.

PMID- 28753963
TI  - The Combined Intervention with Germinated Vigna radiata and Aerobic Interval
      Training Protocol Is an Effective Strategy for the Treatment of Non-Alcoholic
      Fatty Liver Disease (NAFLD) and Other Alterations Related to the Metabolic
      Syndrome in Zucker Rats.
AB  - Metabolic syndrome (MetS) is a group of related metabolic alterations that
      increase the risk of developing non-alcoholic fatty liver disease (NAFLD).
      Several lifestyle interventions based on dietary treatment with functional
      ingredients and physical activity are being studied as alternative or
      reinforcement treatments to the pharmacological ones actually in use. In the
      present experiment, the combined treatment with mung bean (Vigna radiata), a
      widely used legume with promising nutritional and health benefits that was
      included in the experimental diet as raw or 4 day-germinated seed flour, and
      aerobic interval training protocol (65-85% VO2 max) has been tested in lean and
      obese Zucker rats following a 2 * 2 * 2 (2 phenotypes, 2 dietary interventions, 2
      lifestyles) factorial ANOVA (Analysis of Variance) statistical analysis.
      Germination of V. radiata over a period of four days originated a significant
      protein hydrolysis leading to the appearance of low molecular weight peptides.
      The combination of 4 day-germinated V. radiata and aerobic interval training was
      more efficient compared to raw V. radiata at improving the aerobic capacity and
      physical performance, hepatic histology and functionality, and plasma lipid
      parameters as well as reverting the insulin resistance characteristic of the
      obese Zucker rat model. In conclusion, the joint intervention with legume sprouts
      and aerobic interval training protocol is an efficient treatment to improve the
      alterations of glucose and lipid metabolism as well as hepatic histology and
      functionality related to the development of NAFLD and the MetS.

PMID- 28753964
TI  - The Limpopo Non-Metropolitan Drinking Water Supplier Response to a Diagnostic
      Tool for Technical Compliance.
AB  - Water services providers should supply water that is fit for human consumption,
      taking into account multi-barrier approaches and technical aspects such as design
      aspects, operation monitoring, final water quality compliance monitoring, plant
      monitoring practices, maintenance, and risk management practices. Against this
      background, this study focused on applying the diagnostic tool for technical
      compliance as well as assessing the compliance of water treatment plants with
      management norms. Six plants in the Vhembe District Municipality were selected;
      the Vondo, Malamulele, Mutshedzi, and Mutale plants (conventional), and the
      Dzingahe and Tshedza package plants. During the first assessment, four
      (Malamulele, Mutshedzi, Mutale and Dzingahe) plants scored between 44% and 49%
      and achieved Class 3 certification, revealing serious challenges requiring
      immediate intervention. Two water plants (Vondo and Tshedza, scoring 53% and 63%,
      respectively) were in the Class 2 category, revealing serious challenges
      requiring attention and improvement. During the second assessment, all plants
      scored between 63% and 87% (Class 2 category). The greatest improvement (30%) was
      noted for the Dzingahe and Tshedza plants, followed by the Malamulele plant,
      while the Mutale, Vondo, and Mutshedzi plants improved their scores by 20%, 17%
      and 14%, respectively. After corrective actions and re-measurement, no plant
      complied. It is recommended that Water Services Providers (WSPs) regularly apply
      the diagnostic tools and water safety plans as developed in order to comply with
      applicable standards.

PMID- 28753965
TI  - Evaluation of Fitness and the Balance Levels of Children with a Diagnosis of
      Juvenile Idiopathic Arthritis: A Pilot Study.
AB  - Background: Juvenile idiopathic arthritis is a main cause of physical disability
      and has high economic costs for society. The purpose of this study was to assess
      the fitness levels and the postural and balance deficits with a specific test
      battery. Methods: Fifty-six subjects were enrolled in this study. Thirty-nine
      healthy subjects were included in the control group and seventeen in the juvenile
      idiopathic arthritis group. All subjects were evaluated using a posturography
      system. The fitness level was evaluated with a battery of tests (Abalakov test,
      sit-up test, hand grip test, backsaver sit and reach, the toe touch test). An
      unpaired t-test was used to determine differences. Pearson's correlation
      coefficient was used to evaluate the correlation between the tests. Results: The
      battery of tests demonstrated that subjects in the juvenile idiopathic arthritis
      group have lower fitness levels compared to the control group. The juvenile
      idiopathic arthritis group showed low postural control with respect to the
      control group. Pearson analysis of the juvenile idiopathic arthritis group data
      showed significant correlations between variables. Pearson's results from the
      control group data showed a similar trend. Conclusions: The results suggest that
      the battery of tests used could be an appropriate tool. However, we highlight
      that these conclusions need to be supported by other studies with a larger
      population scale.

PMID- 28753966
TI  - Identification of a Novel Vasodilatory Octapeptide from the Skin Secretion of the
      African Hyperoliid Frog, Kassina senegalensis.
AB  - The defensive skin secretions of amphibians continue to be an excellent source of
      novel biologically-active peptides. Here we report the identification and
      pharmacological activity of a novel C-terminally amided myotropic octapeptide
      from the skin secretion of the African hyperoliid frog, Kassina senegalensis. The
      8-amino acid peptide has the following primary structure: WMSLGWSL-amide and has
      a molecular mass of 978 Da. The primary structure and organisation of the
      biosynthetic precursor of WL-8 amide was successfully deduced from cloned skin
      secretion-derived cDNA. The open-reading frame encoded a single copy of WL-8,
      located at the C-terminus. Synthetic WL-8 amide was found to cause relaxation of
      rat tail artery smooth muscle with an EC50 of 25.98 nM. This peptide is unique in
      terms of its primary structure and is unlike any other peptide previously
      isolated from an amphibian source which has been archived in the NCBI database.
      WL-8 amide thus represents the prototype of a novel family of myotropic peptide
      from amphibian defensive skin secretions.

PMID- 28753967
TI  - Drosophila: Retrotransposons Making up Telomeres.
AB  - Drosophila and extant species are the best-studied telomerase exception. In this
      organism, telomere elongation is coupled with targeted retrotransposition of
      Healing Transposon (HeT-A) and Telomere Associated Retrotransposon (TART) with
      sporadic additions of Telomere Associated and HeT-A Related (TAHRE), all three
      specialized non-Long Terminal Repeat (non-LTR) retrotransposons. These three very
      special retroelements transpose in head to tail arrays, always in the same
      orientation at the end of the chromosomes but never in interior locations.
      Apparently, retrotransposon and telomerase telomeres might seem very different,
      but a detailed view of their mechanisms reveals similarities explaining how the
      loss of telomerase in a Drosophila ancestor could successfully have been replaced
      by the telomere retrotransposons. In this review, we will discover that although
      HeT-A, TART, and TAHRE are still the only examples to date where their targeted
      transposition is perfectly tamed into the telomere biology of Drosophila, there
      are other examples of retrotransposons that manage to successfully integrate
      inside and at the end of telomeres. Because the aim of this special issue is
      viral integration at telomeres, understanding the base of the telomerase
      exceptions will help to obtain clues on similar strategies that mobile elements
      and viruses could have acquired in order to ensure their survival in the host
      genome.

PMID- 28753968
TI  - Differential miR-346 and miR-582-3p Expression in Association with Selected
      Maternal and Fetal Complications.
AB  - Several miRNAs are expressed in human gestational tissue, and some have been
      shown to be associated with placental dysfunction and complicated pregnancy
      outcomes. To investigate the roles of miR-346 and miR-582-3p in adverse obstetric
      events, we analyzed these 2 miRNAs in three samples (maternal blood, umbilical
      cord blood and placenta) obtained from pregnant women in four groups, including
      healthy control (n = 60), preeclampsia (n = 31), preterm delivery (n = 29) and
      small for gestational age (n = 19) patients. The expression levels of miR-346 and
      miR-582-3p in all included adverse obstetric outcome groups were significantly
      higher in the maternal plasma samples but lower in the placenta samples (all p
      value < 0.05). In addition, the miR-346 expression levels in fetal cord blood
      were also significantly lower in all of the included adverse obstetric outcome
      groups (all p < 0.05). Multivariate analysis of the three specimens after
      adjusting for maternal age and gestational age at delivery gave the same results.
      In conclusion, aberrant miR-346 and miR-582-3p expression level in pregnancy was
      associated with multiple maternal and fetal complications. Their differential
      expression in maternal blood, umbilical cord blood and placenta could be
      potential biomarkers or therapeutic targets for adverse obstetric outcomes.

PMID- 28753969
TI  - The Hydrogen Sulfide-Vitamin B12-Folic Acid Axis: An Intriguing Issue in Chronic
      Kidney Disease. A Comment on Toohey JI: "Possible Involvement of Hydrosulfide in
      B12-Dependent Methyl Group Transfer". Molecules 2017, 22, 582, pii: E582.

PMID- 28753970
TI  - Reversed-Phase UHPLC Enantiomeric Separation of Rasagiline Salts Using a
      Chiralpak(r) AGP Column.
AB  - We report the first rapid ultra-high performance liquid chromatographic (UHPLC)
      enantiomeric reversed-phase separation of rasagiline mesylate and its tartrate
      salts using a Chiralpak(r) AGP column (50 mm * 2.1 mm, 5 MUm) as a stationary
      phase. This method was developed as an alternative to the usage of previously
      reported normal-phase chiral LC columns for isomer separation. Our method is
      based on an isocratic approach using a mixture of ammonium acetate and isopropyl
      alcohol (90:10, v/v) as the mobile phase (0.6 mL/min flow rate). The detection
      limit (at a detection wavelength of 210 nm) and quantification limit for the
      rasagiline enantiomers were 0.06 and 0.2 MUg/mL, respectively. This method is
      compatible with the UHPLC-MS technique. The successful separation of rasagiline
      and its enantiomer was confirmed by determining the corresponding specific
      optical rotation values. Our method will be applicable for detecting rasagiline
      enantiomers during the control of manufacturing processes, and for use in rapid
      analysis for quality control in pharmaceutical industry to obtain optically pure
      pharmaceutical substances. This method was validated in terms of its precision,
      limit of detection, limit of quantification, linearity, accuracy, robustness,
      ruggedness, specificity, forced degradation, and solution stability, according to
      International Council on Harmonization Validation Guidelines Q2 (R1).

PMID- 28753971
TI  - Spatio-Temporal Variation of Longevity Clusters and the Influence of Social
      Development Level on Lifespan in a Chinese Longevous Area (1982-2010).
AB  - The study aims to determine the spatial and temporal variation of a longevous
      region and explore the correlation between longevity and socioeconomic
      development. Population data at the township level were obtained from the last
      four population censuses (1982-2010). Five main lifespan indicators and the Human
      Development Index (HDI) were calculated. Getis-Ord G*, Gravity modeling, and
      Pearson's r between lifespan indicators and HDI were applied. In this study, a
      stable longevous gathering area was discovered in Hechi during different periods.
      Under the influence of social and economic development, more longevous areas
      appeared. However, the effects of genetic and natural environmental factors on
      longevity were always dominant in this remote and mountainous city. Furthermore,
      longevity indicators lacked any significant correlation with life expectancy. No
      significant positive correlation was detected between lifespan indicators and
      HDI. Thus, we conclude that lifespan indicators can determine the spatial
      distribution and variation pattern of longevity from multiple dimensions. The
      geographical scope of longevity in Hechi City is gradually expanding, and
      significant spatial clustering was detected in southwestern, southern, and
      eastern parts of Hechi. This study also found that social economic development is
      likely to have a certain impact on new longevous areas, but their role on extreme
      longevity is not significant.

PMID- 28753973
TI  - Toward the Fabrication of Advanced Nanofiltration Membranes by Controlling
      Morphologies and Mesochannel Orientations of Hexagonal Lyotropic Liquid Crystals.
AB  - Water scarcity has been recognized as one of the major threats to human activity,
      and, therefore, water purification technologies are increasingly drawing
      attention worldwide. Nanofiltration (NF) membrane technology has been proven to
      be an efficient and cost-effective way in terms of the size and continuity of the
      nanostructure. Using a template based on hexagonal lyotropic liquid crystals
      (LLCs) and partitioning monomer units within this structure for subsequent photo
      polymerisation presents a unique path for the fabrication of NF membranes,
      potentially producing pores of uniform size, ranging from 1 to 5 nm, and large
      surface areas. The subsequent orientation of this pore network in a direction
      normal to a flat polymer film that provides ideal transport properties associated
      with continuous pores running through the membrane has been achieved by the
      orientation of hexagonal LLCs through various strategies. This review presents
      the current progresses on the strategies for structure retention from a hexagonal
      LLCs template and the up-to-date techniques used for the reorientation of
      mesochanels for continuity through the whole membrane.

PMID- 28753972
TI  - Food-Derived Antioxidant Polysaccharides and Their Pharmacological Potential in
      Neurodegenerative Diseases.
AB  - Oxidative stress is known to impair architecture and function of cells, which may
      lead to various chronic diseases, and therefore therapeutic and nutritional
      interventions to reduce oxidative damages represent a viable strategy in the
      amelioration of oxidative stress-related disorders, including neurodegenerative
      diseases. Over the past decade, a variety of natural polysaccharides from
      functional and medicinal foods have attracted great interest due to their
      antioxidant functions such as scavenging free radicals and reducing oxidative
      damages. Interestingly, these antioxidant polysaccharides are also found to
      attenuate neuronal damages and alleviate cognitive and motor decline in a range
      of neurodegenerative models. It has recently been established that the
      neuroprotective mechanisms of polysaccharides are related to oxidative stress
      related pathways, including mitochondrial function, antioxidant defense system
      and pathogenic protein aggregation. Here, we first summarize the current status
      of antioxidant function of food-derived polysaccharides and then attempt to
      appraise their anti-neurodegeneration activities.

PMID- 28753974
TI  - A Noncontact Dibutyl Phthalate Sensor Based on a Wireless-Electrodeless QCM-D
      Modified with Nano-Structured Nickel Hydroxide.
AB  - Dibutyl phthalate (DBP) is a widely used plasticizer which has been found to be a
      reproductive and developmental toxicant and ubiquitously existing in the air. A
      highly sensitive method for DBP monitoring in the environment is urgently needed.
      A DBP sensor based on a homemade wireless-electrodeless quartz crystal
      microbalance with dissipation (QCM-D) coated with nano-structured nickel
      hydroxide is presented. With the noncontact configuration, the sensing system
      could work at a higher resonance frequency (the 3rd overtone) and the response of
      the system was even more stable compared with a conventional quartz crystal
      microbalance (QCM). The sensor achieved a sensitivity of 7.3 Hz/ppb to DBP in a
      concentration range of 0.4-40 ppb and an ultra-low detection limit of 0.4 ppb of
      DBP has also been achieved.

PMID- 28753975
TI  - Classification of Alzheimer's Patients through Ubiquitous Computing.
AB  - Functional data analysis and artificial neural networks are the building blocks
      of the proposed methodology that distinguishes the movement patterns among c's
      patients on different stages of the disease and classifies new patients to their
      appropriate stage of the disease. The movement patterns are obtained by the
      accelerometer device of android smartphones that the patients carry while moving
      freely. The proposed methodology is relevant in that it is flexible on the type
      of data to which it is applied. To exemplify that, it is analyzed a novel real
      three-dimensional functional dataset where each datum is observed in a different
      time domain. Not only is it observed on a difference frequency but also the
      domain of each datum has different length. The obtained classification success
      rate of 83 % indicates the potential of the proposed methodology.

PMID- 28753976
TI  - Effects of Assault Type on Cognitive Behaviour Therapy for Coexisting Depression
      and Alcohol Misuse.
AB  - Although assault exposure is common in mental health and substance misusing
      populations, screening for assaults in treatment settings is frequently
      overlooked. This secondary analysis explored the effects of past sexual (SA) and
      physical (PA) assault on depression, alcohol misuse, global functioning and
      attrition in the Depression and Alcohol Integrated and Single focussed
      Intervention (DAISI) project, whose participants (N = 278) received cognitive
      behaviour therapy (CBT) for their depression and/or alcohol misuse. Of the 278
      DAISI participants, 220 consented to screening for past assault (either by a
      stranger or non-stranger) at baseline. Depression, alcohol, and global
      functioning assessments were administered at baseline and 3, 12, 24, and 36
      months post baseline. A between-group analysis was used to assess differences
      between SA and No SA, and PA and No PA groupings, on adjusted mean treatment
      outcomes across all assessment periods. SA and PA participants had similar mean
      symptom reductions compared to No SA and No PA participants except for lower
      depression and global functioning change scores at the 12-month follow-up. People
      with coexisting depression and alcohol misuse reporting SA or PA can respond well
      to CBT for depression and alcohol misuse. However, follow-up is recommended in
      order to monitor fluctuations in outcomes.

PMID- 28753977
TI  - In Vitro Preservation of Transgenic Tomato (Solanum lycopersicum L.) Plants
      Overexpressing the Stress-Related SlAREB1 Transcription Factor.
AB  - In vitro preservation of transgenic tomato lines overexpressing the stress
      responsive transcription factor SlAREB1 was studied by using slow growth and
      cryopreservation techniques. Slow growth preservation was performed by using
      different concentrations of sucrose (0, 100, 200, 300 mm) and abscisic acid (0,
      4, 8, 12 MUm) in Murashige and Skoog (MS) media, while cryopreservation was
      conducted by using encapsulation dehydration, V-cryoplates and seeds. Significant
      differences were observed between tested lines grown on MS media supplemented
      with 200 mm sucrose where transgenic lines overexpressing SlAREB1 showed improved
      growth when compared with negative control. The addition of abscisic acid (ABA)
      to the preservation media affected negatively transgenic lines growth and
      development when compared with ABA-free media. In encapsulation dehydration, non
      cryopreserved transgenic lines overexpressing SlAREB1 pretreated in 0.8 M sucrose
      for 1 day and subjected to different dehydration periods showed significantly
      higher survival percentages when compared with negative control. For V-cryoplates
      technique, cryopreserved transgenic lines overexpressing SlAREB1 treated in 0.3 M
      sucrose for 3 days with or without cold acclimatization showed significantly
      higher survival percentages when compared with the negative control. Seed
      cryopreservation was performed successfully with a clear reduction in germination
      percentage in transgenic lines overexpressing high levels of SlAREB1. In
      conclusion, transgenic tomato lines overexpressing SlAREB1 were found to improve
      tolerance against different abiotic stresses associated with different in vitro
      preservation protocols.

PMID- 28753978
TI  - Seed-in-Soil: Pancreatic Cancer Influenced by Tumor Microenvironment.
AB  - Pancreatic ductal adenocarcinoma is a fatal malignancy with a five-year survival
      rate lower than 7%, and most patients dying within six months of diagnosis. The
      factors that contribute to the aggressiveness of the disease include, but are not
      limited to: late diagnosis, prompt metastasis to adjacent vital organs, poor
      response, and resistance to anticancer treatments. This malignancy is uniquely
      associated with desmoplastic stroma that accounts for 80% of tumor mass.
      Understanding the biology of stroma can aid the discovery of innovative
      strategies for eradicating this lethal cancer in the future. This review
      highlights the critical components in the stroma and how they interact with the
      cancer cells to convey the devastating tumor progression.

PMID- 28753979
TI  - Lack of Association between Hepatitis C Virus core Gene Variation 70/91aa and
      Insulin Resistance.
AB  - The role of hepatitis C virus (HCV) in insulin resistance (IR) is not fully
      understood. The aim of this study was to determine the impact of amino acid (aa)
      substitutions in the core region of HCV according to IR and to identify clinical
      and laboratory associations. Ninety-two treatment-naive HCV patients were
      recruited to determine laboratory data and blood cell count. IR was determined
      using Homeostasis Model Assessment (HOMA) index where IR was defined as HOMA >=2.
      HCV RNA load and genotype were determined by Abbott Real time HCV. HCV core
      region was determined by direct nucleotide sequencing. Bivariate analysis was
      conducted using HOMA IR >=2 as a dependent factor. IR prevalence was 43.5% (n =
      40), vitamin D sufficiency was found in 76.1% (n = 70) and 72.8% (n = 67) had
      advanced liver fibrosis. In the bivariate analyses, elevated values of gammaGT (p
      = 0.024) and fibrosis staging (p = 0.004) were associated with IR, but IR was not
      related to core mutations. The presence of glutamine in position 70 was
      associated with low vitamin D concentration (p = 0.005). In the multivariate
      analysis, no variable was independently associated with HOMA-IR. In conclusion,
      lack of association between IR and HCV core mutations in positions 70 and 91
      suggests that genetic variability of this region has little impact on IR.

PMID- 28753980
TI  - Transgenerational Social Stress Alters Immune-Behavior Associations and the
      Response to Vaccination.
AB  - Similar to the multi-hit theory of schizophrenia, social behavior pathologies are
      mediated by multiple factors across generations, likely acting additively,
      synergistically, or antagonistically. Exposure to social adversity, especially
      during early life, has been proposed to induce depression symptoms through immune
      mediated mechanisms. Basal immune factors are altered in a variety of
      neurobehavioral models. In the current study, we assessed two aspects of a
      transgenerational chronic social stress (CSS) rat model and its effects on the
      immune system. First, we asked whether exposure of F0 dams and their F1 litters
      to CSS changes basal levels of IL-6, TNF, IFN-gamma, and social behavior in CSS
      F1 female juvenile rats. Second, we asked whether the F2 generation could
      generate normal immunological responses following vaccination with Mycobacterium
      bovis Bacillus Calmette-Guerin (BCG). We report several changes in the
      associations between social behaviors and cytokines in the F1 juvenile offspring
      of the CSS model. It is suggested that changes in the immune-behavior
      relationships in F1 juveniles indicate the early stages of immune mediated
      disruption of social behavior that becomes more apparent in F1 dams and the F2
      generation. We also report preliminary evidence of elevated IL-6 and impaired
      interferon-gamma responses in BCG-vaccinated F2 females. In conclusion,
      transgenerational social stress alters both immune-behavior associations and
      responses to vaccination. It is hypothesized that the effects of social stress
      may accumulate over generations through changes in the immune system,
      establishing the immune system as an effective preventative or treatment target
      for social behavior pathologies.

PMID- 28753981
TI  - A Membrane-Fusion Model That Exploits a beta-to-alpha Transition in the
      Hydrophobic Domains of Syntaxin 1A and Synaptobrevin 2.
AB  - Parallel zippering of the SNARE domains of syntaxin 1A/B, SNAP-25, and
      VAMP/synaptobrevin 2 is widely regarded as supplying the driving force for
      exocytotic events at nerve terminals and elsewhere. However, in spite of
      intensive research, no consensus has been reached concerning the molecular
      mechanism by which these SNARE proteins catalyze membrane fusion. As an
      alternative to SNARE-based models, a scenario was developed in which
      synaptotagmin 1 (or, 2) can serve as a template to guide lipid movements that
      underlie fast, synchronous exocytosis at nerve terminals. This "dyad model"
      advanced a novel proposal concerning the membrane disposition of the
      palmitoylated, cysteine-rich region of these synaptotagmins. Unexpectedly, it now
      emerges that a similar principle can be exploited to reveal how the hydrophobic,
      carboxyl-terminal domains of syntaxin 1A and synaptobrevin 2 can perturb membrane
      structure at the interface between a docked synaptic vesicle and the plasma
      membrane. These "beta-to-alpha transition" models will be compared and contrasted
      with other proposals for how macromolecules are thought to intervene to drive
      membrane fusion.

PMID- 28753982
TI  - Th17 in Animal Models of Rheumatoid Arthritis.
AB  - IL-17-secreting helper CD4 T cells (Th17 cells) constitute a newly identified
      subset of helper CD4 T cells that play a key role in the development of
      rheumatoid arthritis (RA) in its animal models. Recently, several models of
      spontaneous RA, which elucidate the mechanism of RA onset, have been discovered.
      These animal models shed new light on the role of Th17 in the development of
      autoimmune arthritis. Th17 cells coordinate inflammation and promote joint
      destruction, acting on various cells, including neutrophils, macrophages,
      synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17
      cells under conditions of inflammation. In this review, the pathogenic role of
      Th17 cells in arthritis development, which was revealed by the recent animal
      models of RA, is discussed.

PMID- 28753983
TI  - Outcome of Full-Thickness Macular Hole Surgery in Choroideremia.
AB  - The development of a macular hole is relatively common in retinal dystrophies
      eligible for gene therapy such as choroideremia. However, the subretinal delivery
      of gene therapy requires an uninterrupted retina to allow dispersion of the viral
      vector. A macular hole may thus hinder effective gene therapy. Little is known
      about the outcome of macular hole surgery and its possible beneficial and/or
      adverse effects on retinal function in patients with choroideremia. We describe a
      case of a unilateral full-thickness macular hole (FTMH) in a 45year-old
      choroideremia patient (c.1349_1349+2dup mutation in CHM gene) and its management.
      Pars plana vitrectomy with internal limiting membrane (ILM) peeling and 20% SF6
      gas tamponade was performed, and subsequent FTMH closure was confirmed at 4
      weeks, 3 months and 5 months postoperatively. No postoperative adverse events
      occurred, and fixation stability improved on microperimetry from respectively 11%
      and 44% of fixation points located within a 1 degrees  and 2 degrees  radius,
      preoperatively, to 94% and 100% postoperatively. This case underlines that pars
      plana vitrectomy with ILM peeling and gas tamponade can successfully close a FTMH
      in choroideremia patients, with subsequent structural and functional improvement.
      Macular hole closure may be important for patients to be eligible for future
      submacular gene therapy.

PMID- 28753984
TI  - Dietary Modulation of Oxidative Stress in Alzheimer's Disease.
AB  - Cells generate unpaired electrons, typically via oxygen- or nitrogen-based by
      products during normal cellular respiration and under stressed situations. These
      pro-oxidant molecules are highly unstable and may oxidize surrounding cellular
      macromolecules. Under normal conditions, the reactive oxygen or nitrogen species
      can be beneficial to cell survival and function by destroying and degrading
      pathogens or antigens. However, excessive generation and accumulation of the
      reactive pro-oxidant species over time can damage proteins, lipids,
      carbohydrates, and nucleic acids. Over time, this oxidative stress can contribute
      to a range of aging-related degenerative diseases such as cancer, diabetes,
      macular degeneration, and Alzheimer's, and Parkinson's diseases. It is well
      accepted that natural compounds, including vitamins A, C, and E, beta-carotene,
      and minerals found in fruits and vegetables are powerful anti-oxidants that offer
      health benefits against several different oxidative stress induced degenerative
      diseases, including Alzheimer's disease (AD). There is increasing interest in
      developing anti-oxidative therapeutics to prevent AD. There are contradictory and
      inconsistent reports on the possible benefits of anti-oxidative supplements;
      however, fruits and vegetables enriched with multiple anti-oxidants (e.g.,
      flavonoids and polyphenols) and minerals may be highly effective in attenuating
      the harmful effects of oxidative stress. As the physiological activation of
      either protective or destructive pro-oxidant behavior remains relatively unclear,
      it is not straightforward to relate the efficacy of dietary anti-oxidants in
      disease prevention. Here, we review oxidative stress mediated toxicity associated
      with AD and highlight the modulatory roles of natural dietary anti-oxidants in
      preventing AD.

PMID- 28753985
TI  - New Biomarkers and Diagnostic Tools for the Management of Fever in Low- and
      Middle-Income Countries: An Overview of the Challenges.
AB  - A lack of simple, inexpensive, and rapid diagnostic tests for febrile illnesses
      other than malaria leads to overtreatment with antibiotics for those who test
      negative for malaria, and contributes to the global rise in antimicrobial
      resistance. New tests for the detection of host biomarkers provide promising
      tools to differentiate bacterial from non-bacterial infections in febrile
      patients. However, most available biomarker tests are not currently used in
      resource-limited settings, and very few evaluations have been performed in low-
      and middle-income country populations with non-severe febrile illness. As a
      result, our knowledge of the performance of these tests in settings with high
      prevalence of infectious and poverty-related diseases such as malaria, HIV,
      malnutrition and intestinal parasites is poor. This paper describes challenges
      faced during the process of getting to an approved test, including difficulties
      in selecting the most appropriate fever biomarkers; suitable study designs and
      sites for test evaluations; lack of available reference tests to evaluate the
      performance of new tests; and lack of clear regulatory pathways to introduce such
      tests. As many new biomarker assays are in development, understanding these
      challenges will better enable those working in this area to address them during
      product development.

PMID- 28753986
TI  - Brain Interaction during Cooperation: Evaluating Local Properties of Multiple
      Brain Network.
AB  - Subjects' interaction is the core of most human activities. This is the reason
      why a lack of coordination is often the cause of missing goals, more than
      individual failure. While there are different subjective and objective measures
      to assess the level of mental effort required by subjects while facing a
      situation that is getting harder, that is, mental workload, to define an
      objective measure based on how and if team members are interacting is not so
      straightforward. In this study, behavioral, subjective and synchronized
      electroencephalographic data were collected from couples involved in a
      cooperative task to describe the relationship between task difficulty and team
      coordination, in the sense of interaction aimed at cooperatively performing the
      assignment. Multiple-brain connectivity analysis provided information about the
      whole interacting system. The results showed that averaged local properties of a
      brain network were affected by task difficulty. In particular, strength changed
      significantly with task difficulty and clustering coefficients strongly
      correlated with the workload itself. In particular, a higher workload
      corresponded to lower clustering values over the central and parietal brain
      areas. Such results has been interpreted as less efficient organization of the
      network when the subjects' activities, due to high workload tendencies, were less
      coordinated.

PMID- 28753987
TI  - Chemical Analysis of Astragali Complanati Semen and Its Hypocholesterolemic
      Effect Using Serum Metabolomics Based on Gas Chromatography-Mass Spectrometry.
AB  - The hypocholesterolemic protective effect of the dried seed of Astragalus
      complanatus (ACS) was investigated in rats fed with normal diet, high cholesterol
      diet (HCD), and HCD plus 70% ethanol extract of ACS (600 mg/kg/day) by oral
      gavage for four weeks. ACS extract was tested to be rich in antioxidants, which
      may be contributed to its high content of phenolic compounds. Consumption of ACS
      remarkably suppressed the elevated total cholesterol (p < 0.01) and LDL-C (p <
      0.001) induced by HCD. Chemical constituents of ACS extract were analyzed by
      ultra-performance liquid chromatography coupled with electrospray ionization
      orbitrap mass spectrometry and the results showed that the ACS extract mainly
      consisted of phenolic compounds including flavonoids and flavonoid glycosides. In
      addition, based on the serum fatty acid profiles, elucidated using gas
      chromatography-mass spectrometry, free and esterified fatty acids including
      docosapentaenoic acid, adrenic acid, dihomo-gamma-linolenic acid and arachidonic
      acid were regulated in ACS treatment group. Western blot results further
      indicated the protein expression of peroxisome proliferator-activated receptor
      alpha (PPARalpha) (p < 0.05) in liver was upregulated in ACS treatment group. To
      conclude, our results clearly demonstrated that ACS provides beneficial effect on
      lowering HCD associated detrimental change.

PMID- 28753988
TI  - Evolutionary Significance of Wolbachia-to-Animal Horizontal Gene Transfer: Female
      Sex Determination and the f Element in the Isopod Armadillidium vulgare.
AB  - An increasing number of horizontal gene transfer (HGT) events from bacteria to
      animals have been reported in the past years, many of which involve Wolbachia
      bacterial endosymbionts and their invertebrate hosts. Most transferred Wolbachia
      genes are neutrally-evolving fossils embedded in host genomes. A remarkable case
      of Wolbachia HGT for which a clear evolutionary significance has been
      demonstrated is the "f element", a nuclear Wolbachia insert involved in female
      sex determination in the terrestrial isopod Armadillidium vulgare. The f element
      represents an instance of bacteria-to-animal HGT that has occurred so recently
      that it was possible to infer the donor (feminizing Wolbachia closely related to
      the wVulC Wolbachia strain of A. vulgare) and the mechanism of integration (a
      nearly complete genome inserted by micro-homology-mediated recombination). In
      this review, we summarize our current knowledge of the f element and discuss
      arising perspectives regarding female sex determination, unstable inheritance,
      population dynamics and the molecular evolution of the f element. Overall, the f
      element unifies three major areas in evolutionary biology: symbiosis, HGT and sex
      determination. Its characterization highlights the tremendous impact sex ratio
      distorters can have on the evolution of sex determination mechanisms and sex
      chromosomes in animals and plants.

PMID- 28753989
TI  - Selectively Enhanced UV-A Photoresponsivity of a GaN MSM UV Photodetector with a
      Step-Graded AlxGa1-xN Buffer Layer.
AB  - The UV-to-visible rejection ratio is one of the important figure of merits of GaN
      based UV photodetectors. For cost-effectiveness and large-scale fabrication of
      GaN devices, we tried to grow a GaN epitaxial layer on silicon substrate with
      complicated buffer layers for a stress-release. It is known that the structure of
      the buffer layers affects the performance of devices fabricated on the GaN
      epitaxial layers. In this study, we show that the design of a buffer layer
      structure can make effect on the UV-to-visible rejection ratio of GaN UV
      photodetectors. The GaN photodetector fabricated on GaN-on-silicon substrate with
      a step-graded AlxGa-xN buffer layer has a highly-selective photoresponse at 365
      nm wavelength. The UV-to-visible rejection ratio of the GaN UV photodetector with
      the step-graded AlxGa1-xN buffer layer was an order-of-magnitude higher than that
      of a photodetector with a conventional GaN/AlN multi buffer layer. The maximum
      photoresponsivity was as high as 5 * 10-2 A/W. This result implies that the
      design of buffer layer is important for photoresponse characteristics of GaN UV
      photodetectors as well as the crystal quality of the GaN epitaxial layers.

PMID- 28753990
TI  - Lifetime Maximization via Hole Alleviation in IoT Enabling Heterogeneous Wireless
      Sensor Networks.
AB  - In Internet of Things (IoT) enabled Wireless Sensor Networks (WSNs), there are
      two major factors which degrade the performance of the network. One is the void
      hole which occurs in a particular region due to unavailability of forwarder
      nodes. The other is the presence of energy hole which occurs due to imbalanced
      data traffic load on intermediate nodes. Therefore, an optimum transmission
      strategy is required to maximize the network lifespan via hole alleviation. In
      this regard, we propose a heterogeneous network solution that is capable to
      balance energy dissipation among network nodes. In addition, the divide and
      conquer approach is exploited to evenly distribute number of transmissions over
      various network areas. An efficient forwarder node selection is performed to
      alleviate coverage and energy holes. Linear optimization is performed to validate
      the effectiveness of our proposed work in term of energy minimization.
      Furthermore, simulations are conducted to show that our claims are well grounded.
      Results show the superiority of our work as compared to the baseline scheme in
      terms of energy consumption and network lifetime.

PMID- 28753991
TI  - Hierarchical Stereo Matching in Two-Scale Space for Cyber-Physical System.
AB  - Dense disparity map estimation from a high-resolution stereo image is a very
      difficult problem in terms of both matching accuracy and computation efficiency.
      Thus, an exhaustive disparity search at full resolution is required. In general,
      examining more pixels in the stereo view results in more ambiguous
      correspondences. When a high-resolution image is down-sampled, the high-frequency
      components of the fine-scaled image are at risk of disappearing in the coarse
      resolution image. Furthermore, if erroneous disparity estimates caused by missing
      high-frequency components are propagated across scale space, ultimately, false
      disparity estimates are obtained. To solve these problems, we introduce an
      efficient hierarchical stereo matching method in two-scale space. This method
      applies disparity estimation to the reduced-resolution image, and the disparity
      result is then up-sampled to the original resolution. The disparity estimation
      values of the high-frequency (or edge component) regions of the full-resolution
      image are combined with the up-sampled disparity results. In this study, we
      extracted the high-frequency areas from the scale-space representation by using
      difference of Gaussian (DoG) or found edge components, using a Canny operator.
      Then, edge-aware disparity propagation was used to refine the disparity map. The
      experimental results show that the proposed algorithm outperforms previous
      methods.

PMID- 28753992
TI  - Applicability of Metal Nanoparticles in the Detection and Monitoring of Hepatitis
      B Virus Infection.
AB  - Chronic infection with the hepatitis B virus (HBV) can lead to liver failure and
      can cause liver cirrhosis and hepatocellular carcinoma (HCC). Reliable means for
      detecting and monitoring HBV infection are essential to identify patients in need
      of therapy and to prevent HBV transmission. Nanomaterials with defined
      electrical, optical, and mechanical properties have been developed to detect and
      quantify viral antigens. In this review, we discuss the challenges in applying
      nanoparticles to HBV antigen detection and in realizing the bio-analytical
      potential of such nanoparticles. We discuss recent developments in generating
      detection platforms based on gold and iron oxide nanoparticles. Such platforms
      increase biological material detection efficiency by the targeted capture and
      concentration of HBV antigens, but the unique properties of nanoparticles can
      also be exploited for direct, sensitive, and specific antigen detection. We
      discuss several studies that show that nanomaterial-based platforms enable
      ultrasensitive HBV antigen detection.

PMID- 28753993
TI  - Disposal Situation of Sewage Sludge from Municipal Wastewater Treatment Plants
      (WWTPs) and Assessment of the Ecological Risk of Heavy Metals for Its Land Use in
      Shanxi, China.
AB  - Land use of sewage sludge is the primary disposal method in Shanxi, accounting
      for 42.66% of all. To determine the ecological risk of heavy metals in sewage
      sludge, contents of seven heavy metals in sewage sludge from 9 municipal waste
      water treatment plants (WWTPs) that had the highest application for land use were
      determined. The order of the measured concentrations was: Zn > Cr > Cu > Ni > Pb
      > As > Cd, and all heavy metals contents were within the threshold limit values
      of the Chinese Control Standards for Pollutants in Sludge from Agriculture Use
      (GB4284-84). Four indices were used to assess the pollution and the ecological
      risk of heavy metals. By the mean values of the geoaccumulation index (Igeo),
      heavy metals were ranked in the following order: Cd > Zn > Cu > As > Cr > Ni >
      Pb. The values showed that the pollution of Zn in station 3 and Cd in station 1,
      2, 3, 4, 8 and 9 were heavily; Cu in station 8 and 9, Zn in station 1, 2, 4, 8
      and 9 and Cd in station 5 and 7 were moderately to heavily, and the accumulation
      of other heavy metals were not significant. The single-factor pollution index
      (PI) suggested that none of the stations had heavy metals contamination, except
      for Cu in station 9, Zn in station 3 and 8, and Cd in station 1 and 9, which were
      at a moderate level. According to the results of the Nemerow's synthetic
      pollution index (PN), sewage sludge from all stations was safe for land use with
      respect to heavy metals contamination, except for stations 3, 8 and 9, which were
      at the warning line. The monomial potential ecological risk coefficient (Eri)
      revealed that heavy metals ecological risks in most stations were low. However,
      station 9 had a moderate risk for Cu; station 6 had a moderate risk, stations 5
      and 7 had high risk, other stations had very high risk for Cd. According to the
      results of the potential ecological risk index (RI), station 1, 8 and 9 had high
      risk; station 2, 3, 4, 5 and 7 had a moderate risk, and station 6 had a low risk.
      The preliminary results indicated that the potential risk of land exposure to
      heavy metals in sewage sludge was relatively low, with Zn and Cd as the main
      contributor to the ecological risk for the applying of sewage sludge on land.
      Additionally, stations 3, 8 and 9 require more attention regarding the land
      applications related to heavy metals pollution.

PMID- 28753994
TI  - Noncontact Sleep Study by Multi-Modal Sensor Fusion.
AB  - Polysomnography (PSG) is considered as the gold standard for determining sleep
      stages, but due to the obtrusiveness of its sensor attachments, sleep stage
      classification algorithms using noninvasive sensors have been developed
      throughout the years. However, the previous studies have not yet been proven
      reliable. In addition, most of the products are designed for healthy customers
      rather than for patients with sleep disorder. We present a novel approach to
      classify sleep stages via low cost and noncontact multi-modal sensor fusion,
      which extracts sleep-related vital signals from radar signals and a sound-based
      context-awareness technique. This work is uniquely designed based on the PSG data
      of sleep disorder patients, which were received and certified by professionals at
      Hanyang University Hospital. The proposed algorithm further incorporates
      medical/statistical knowledge to determine personal-adjusted thresholds and
      devise post-processing. The efficiency of the proposed algorithm is highlighted
      by contrasting sleep stage classification performance between single sensor and
      sensor-fusion algorithms. To validate the possibility of commercializing this
      work, the classification results of this algorithm were compared with the
      commercialized sleep monitoring device, ResMed S+. The proposed algorithm was
      investigated with random patients following PSG examination, and results show a
      promising novel approach for determining sleep stages in a low cost and
      unobtrusive manner.

PMID- 28753995
TI  - The Role of Th17 Cells in the Pathogenesis of Behcet's Disease.
AB  - Behcet's disease (BD) is a polysymptomatic and recurrent systemic vasculitis with
      a chronic course and unknown cause. The pathogenesis of BD has not been fully
      elucidated; however, BD has been considered to be a typical Th1-mediated
      inflammatory disease, characterized by elevated levels of Th1 cytokines such as
      IFN-gamma, IL-2, and TNF-alpha. Recently, some studies reported that Th17
      associated cytokines were increased in BD; thus, Th17 cells and the IL17/IL23
      pathway may play important roles in the pathogenesis of BD. In this chapter, we
      focus on the pathogenic role of Th17 cells in BD.

PMID- 28753996
TI  - Boron Tolerance in Aspergillus nidulans Is Sustained by the SltA Pathway Through
      the SLC-Family Transporters SbtA and SbtB.
AB  - Microbial cells interact with the environment by adapting to external changes.
      Signal transduction pathways participate in both sensing and responding in the
      form of modification of gene expression patterns, enabling cell survival. The
      filamentous fungal-specific SltA pathway regulates tolerance to alkalinity,
      elevated cation concentrations and, as shown in this work, also stress conditions
      induced by borates. Growth of sltA- mutants is inhibited by increasing millimolar
      concentrations of boric acid or borax (sodium tetraborate). In an attempt to
      identify genes required for boron-stress response, we determined the boric acid
      or borax-dependent expression of sbtA and sbtB, orthologs of Saccharomyces
      cerevisiae bor1, and a reduction in their transcript levels in a DeltasltA
      mutant. Deletion of sbtA, but mainly that of sbtB, decreased the tolerance to
      boric acid or borax. In contrast, null mutants of genes coding for additional
      transporters of the Solute Carrier (SLC) family, sB, sbtD or sbtE, showed an
      unaltered growth pattern under the same stress conditions. Taken together, our
      results suggest that the SltA pathway induces, through SbtA and SbtB, the export
      of toxic concentrations of borates, which have largely recognized antimicrobial
      properties.

PMID- 28753997
TI  - Effects of Chlorhexidine-Encapsulated Mesoporous Silica Nanoparticles on the Anti
      Biofilm and Mechanical Properties of Glass Ionomer Cement.
AB  - One of the primary causes for the failure of glass ionomer cement (GIC) is
      secondary caries. To enhance the anti-microbial performance of GIC without
      affecting its mechanical properties, chlorhexidine (CHX) was encapsulated in
      expanded-pore mesoporous silica nanoparticles (pMSN) to synthesize CHX@pMSN.
      CHX@pMSN was added at three mass fractions (1%, 5%, and 10% (w/w)) to GIC powder
      as the experimental groups. Pure GIC was set as the control group. The mechanical
      and anti-biofilm properties of GIC from each group were tested. The results
      demonstrated that CHX was successfully encapsulated on/into pMSN, and the
      encapsulating efficiency of CHX was 44.62% in CHX@pMSN. The anti-biofilm ability
      was significantly enhanced in all experimental groups (p < 0.001) compared with
      that in the control group. CHX was continuously released, and anti-biofilm
      ability was maintained up to 30 days. In addition, the mechanical properties
      (compressive strength, surface hardness, elastic modulus, water sorption, and
      solubility) of 1% (w/w) group were maintained compared with those in the control
      group (p > 0.05). In conclusion, adding 1% (w/w) CHX@pMSN to GIC led to
      conspicuous anti-biofilm ability and had no adverse effect on the mechanical
      properties of this restorative material. This study proposes a new strategy for
      preventing secondary caries by using CHX@pMSN-modified GIC.

PMID- 28753998
TI  - Aptamer-Based Carboxyl-Terminated Nanocrystalline Diamond Sensing Arrays for
      Adenosine Triphosphate Detection.
AB  - Here, we propose simple diamond functionalization by carboxyl termination for
      adenosine triphosphate (ATP) detection by an aptamer. The high-sensitivity label
      free aptamer sensor for ATP detection was fabricated on nanocrystalline diamond
      (NCD). Carboxyl termination of the NCD surface by vacuum ultraviolet excimer
      laser and fluorine termination of the background region as a passivated layer
      were investigated by X-ray photoelectron spectroscopy. Single strand DNA (amide
      modification) was used as the supporting biomolecule to immobilize into the
      diamond surface via carboxyl termination and become a double strand with aptamer.
      ATP detection by aptamer was observed as a 66% fluorescence signal intensity
      decrease of the hybridization intensity signal. The sensor operation was also
      investigated by the field-effect characteristics. The shift of the drain current
      drain voltage characteristics was used as the indicator for detection of ATP.
      From the field-effect characteristics, the shift of the drain current-drain
      voltage was observed in the negative direction. The negative charge direction
      shows that the aptamer is capable of detecting ATP. The ability of the sensor to
      detect ATP was investigated by fabricating a field-effect transistor on the
      modified NCD surface.

PMID- 28753999
TI  - Application of Ammonium Persulfate for Selective Oxidation of Guanines for
      Nucleic Acid Sequencing.
AB  - Nucleic acids can be sequenced by a chemical procedure that partially damages the
      nucleotide positions at their base repetition. Many methods have been reported
      for the selective recognition of guanine. The accurate identification of guanine
      in both single and double regions of DNA and RNA remains a challenging task.
      Herein, we present a new, non-toxic and simple method for the selective
      recognition of guanine in both DNA and RNA sequences via ammonium persulfate
      modification. This strategy can be further successfully applied to the detection
      of 5-methylcytosine by using PCR.

PMID- 28754001
TI  - Using Machine Learning to Discover Latent Social Phenotypes in Free-Ranging
      Macaques.
AB  - Investigating the biological bases of social phenotypes is challenging because
      social behavior is both high-dimensional and richly structured, and biological
      factors are more likely to influence complex patterns of behavior rather than any
      single behavior in isolation. The space of all possible patterns of interactions
      among behaviors is too large to investigate using conventional statistical
      methods. In order to quantitatively define social phenotypes from natural
      behavior, we developed a machine learning model to identify and measure patterns
      of behavior in naturalistic observational data, as well as their relationships to
      biological, environmental, and demographic sources of variation. We applied this
      model to extensive observations of natural behavior in free-ranging rhesus
      macaques, and identified behavioral states that appeared to capture periods of
      social isolation, competition over food, conflicts among groups, and affiliative
      coexistence. Phenotypes, represented as the rate of being in each state for a
      particular animal, were strongly and broadly influenced by dominance rank, sex,
      and social group membership. We also identified two states for which variation in
      rates had a substantial genetic component. We discuss how this model can be
      extended to identify the contributions to social phenotypes of particular genetic
      pathways.

PMID- 28754002
TI  - Pediatric Respiratory Support Technology and Practices: A Global Survey.
AB  - OBJECTIVE: This global survey aimed to assess the current respiratory support
      capabilities for children with hypoxemia and respiratory failure in different
      economic settings. METHODS: An online, anonymous survey of medical providers with
      experience in managing pediatric acute respiratory illness was distributed
      electronically to members of the World Federation of Pediatric Intensive and
      Critical Care Society, and other critical care websites for 3 months. RESULTS:
      The survey was completed by 295 participants from 64 countries, including 28 High
      Income (HIC) and 36 Low- and Middle-Income Countries (LMIC). Most respondents
      (>=84%) worked in urban tertiary care centers. For managing acute respiratory
      failure, endotracheal intubation with mechanical ventilation was the most
      commonly reported form of respiratory support (>=94% in LMIC and HIC). Continuous
      Positive Airway Pressure (CPAP) was the most commonly reported form of non
      invasive positive pressure support (>=86% in LMIC and HIC). Bubble-CPAP was used
      by 36% HIC and 39% LMIC participants. ECMO for acute respiratory failure was
      reported by 45% of HIC participants, compared to 34% of LMIC. Oxygen, air, gas
      humidifiers, breathing circuits, patient interfaces, and oxygen saturation
      monitoring appear widely available. Reported ICU patient to health care provider
      ratios were higher in LMIC compared to HIC. The frequency of respiratory
      assessments was hourly in HIC, compared to every 2-4 h in LMIC. CONCLUSIONS: This
      survey indicates many apparent similarities in the presence of respiratory
      support systems in urban care centers globally, but system quality, quantity, and
      functionality were not established by this survey. LMIC ICUs appear to have
      higher patient to medical staff ratios, with decreased patient monitoring
      frequencies, suggesting patient safety should be a focus during the introduction
      of new respiratory support devices and practices.

PMID- 28754000
TI  - The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your
      Enemies Closer.
AB  - Chemoresistance is a leading cause of morbidity and mortality in cancer and it
      continues to be a challenge in cancer treatment. Chemoresistance is influenced by
      genetic and epigenetic alterations which affect drug uptake, metabolism and
      export of drugs at the cellular levels. While most research has focused on tumor
      cell autonomous mechanisms of chemoresistance, the tumor microenvironment has
      emerged as a key player in the development of chemoresistance and in malignant
      progression, thereby influencing the development of novel therapies in clinical
      oncology. It is not surprising that the study of the tumor microenvironment is
      now considered to be as important as the study of tumor cells. Recent advances in
      technological and analytical methods, especially 'omics' technologies, has made
      it possible to identify specific targets in tumor cells and within the tumor
      microenvironment to eradicate cancer. Tumors need constant support from
      previously 'unsupportive' microenvironments. Novel therapeutic strategies that
      inhibit such microenvironmental support to tumor cells would reduce
      chemoresistance and tumor relapse. Such strategies can target stromal cells,
      proteins released by stromal cells and non-cellular components such as the
      extracellular matrix (ECM) within the tumor microenvironment. Novel in vitro
      tumor biology models that recapitulate the in vivo tumor microenvironment such as
      multicellular tumor spheroids, biomimetic scaffolds and tumor organoids are being
      developed and are increasing our understanding of cancer cell-microenvironment
      interactions. This review offers an analysis of recent developments on the role
      of the tumor microenvironment in the development of chemoresistance and the
      strategies to overcome microenvironment-mediated chemoresistance. We propose a
      systematic analysis of the relationship between tumor cells and their respective
      tumor microenvironments and our data show that, to survive, cancer cells interact
      closely with tumor microenvironment components such as mesenchymal stem cells and
      the extracellular matrix.

PMID- 28754003
TI  - Estimated Nutritive Value of Low-Price Model Lunch Sets Provided to Garment
      Workers in Cambodia.
AB  - BACKGROUND: The establishment of staff canteens is expected to improve the
      nutritional situation of Cambodian garment workers. The objective of this study
      is to assess the nutritive value of low-price model lunch sets provided at a
      garment factory in Phnom Penh, Cambodia. METHODS: Exemplary lunch sets were
      served to female workers through a temporary canteen at a garment factory in
      Phnom Penh. Dish samples were collected repeatedly to examine mean serving sizes
      of individual ingredients. Food composition tables and NutriSurvey software were
      used to assess mean amounts and contributions to recommended dietary allowances
      (RDAs) or adequate intake of energy, macronutrients, dietary fiber, vitamin C
      (VitC), iron, vitamin A (VitA), folate and vitamin B12 (VitB12). RESULTS: On
      average, lunch sets provided roughly one third of RDA or adequate intake of
      energy, carbohydrates, fat and dietary fiber. Contribution to RDA of protein was
      high (46% RDA). The sets contained a high mean share of VitC (159% RDA), VitA
      (66% RDA), and folate (44% RDA), but were low in VitB12 (29% RDA) and iron (20%
      RDA). CONCLUSIONS: Overall, lunches satisfied recommendations of caloric content
      and macronutrient composition. Sets on average contained a beneficial amount of
      VitC, VitA and folate. Adjustments are needed for a higher iron content.
      Alternative iron-rich foods are expected to be better suited, compared to
      increasing portions of costly meat/fish components. Lunch provision at Cambodian
      garment factories holds the potential to improve food security of workers,
      approximately at costs of <1 USD/person/day at large scale. Data on quantitative
      total dietary intake as well as physical activity among workers are needed to
      further optimize the concept of staff canteens.

PMID- 28754004
TI  - Synergistic Interplay between Curcumin and Polyphenol-Rich Foods in the
      Mediterranean Diet: Therapeutic Prospects for Neurofibromatosis 1 Patients.
AB  - Neurofibromas are the hallmark lesions in Neurofibromatosis 1 (NF1); these tumors
      are classified as cutaneous, subcutaneous and plexiform. In contrast to cutaneous
      and subcutaneous neurofibromas, plexiform neurofibromas can grow quickly and
      progress to malignancy. Curcumin, a turmeric-derived polyphenol, has been shown
      to interact with several molecular targets implicated in carcinogenesis. Here, we
      describe the impact of different dietary patterns, namely Mediterranean diet
      (MedDiet) compared to the Western diet (WesDiet), both with or without curcumin,
      on NF1 patients' health. After six months, patients adopting a traditional
      MedDiet enriched with 1200 mg curcumin per day (MedDietCurcumin) presented a
      significant reduction in the number and volume of cutaneous neurofibromas; these
      results were confirmed in subsequent evaluations. Notably, in one patient, a
      large cranial plexiform neurofibroma exhibited a reduction in volume (28%)
      confirmed by Magnetic Resonance Imaging. Conversely, neither unenriched MedDiet
      nor WesDiet enriched with curcumin exhibited any significant positive effect. We
      hypothesize that the combination of a polyphenol-rich Mediterranean diet and
      curcumin was responsible for the beneficial effect observed on NF1. This is, to
      the best of our knowledge, the first experience with curcumin supplementation in
      NF1 patients. Our report suggests that an integrated nutritional approach may
      effectively aid in the management of NF1.

PMID- 28754006
TI  - The Paradox of Ingestion of Dietary Cholesterol in "Vegans"-Reply.
AB  - In a comment on several articles on the vegan dietary pattern, Antoniazzi &
      Acosta-Navarro (2017) mentioned the paradox of the presence of dietary
      cholesterol as a nutritional component in the analysis of the vegan dietary
      pattern [1]. [...].

PMID- 28754005
TI  - Can Early Omega-3 Fatty Acid Exposure Reduce Risk of Childhood Allergic Disease?
AB  - A causal link between increased intake of omega-6 (n-6) polyunsaturated fatty
      acids (PUFAs) and increased incidence of allergic disease has been suggested.
      This is supported by biologically plausible mechanisms, related to the roles of
      eicosanoid mediators produced from the n-6 PUFA arachidonic acid. Fish and fish
      oils are sources of long chain omega-3 (n-3) PUFAs. These fatty acids act to
      oppose the actions of n-6 PUFAs particularly with regard to eicosanoid synthesis.
      Thus, n-3 PUFAs may protect against allergic sensitisation and allergic
      manifestations. Epidemiological studies investigating the association between
      maternal fish intake during pregnancy and allergic outcomes in infants/children
      of those pregnancies suggest protective associations, but the findings are
      inconsistent. Fish oil provision to pregnant women is associated with immunologic
      changes in cord blood. Studies performed to date indicate that provision of fish
      oil during pregnancy may reduce sensitisation to common food allergens and reduce
      prevalence and severity of atopic eczema in the first year of life, with a
      possible persistence until adolescence. A recent study reported that fish oil
      consumption in pregnancy reduces persistent wheeze and asthma in the offspring at
      ages 3 to 5 years. Eating oily fish or fish oil supplementation in pregnancy may
      be a strategy to prevent infant and childhood allergic disease.

PMID- 28754007
TI  - Developmental Expression of HSP60 and HSP10 in the Coilia nasus Testis during
      Upstream Spawning Migration.
AB  - Heat shock protein 60 (HSP60) and heat shock protein 10 (HSP10) are important
      chaperones, which have been proven to have essential roles in mediating the
      correct folding of nuclear encoded proteins imported to mitochondria.
      Mitochondria are known as the power house of the cell, with which it produces
      energy and respires aerobically. In this regard, the obtained HSP60 and HSP10
      have typical characteristics of the HSP60/10 family signature. Their mRNA
      transcripts detected were highest during the developmental phase (in April),
      while the lowest levels were found in the resting phase (after spawning in late
      July). Additionally, the strongest immunolabeling positive signals were found in
      the primary spermatocyte, with lower positive staining in secondary sperm cells,
      and a weak or absent level in the mature sperm. At the electron microscopic
      level, immunogold particles were localized in the mitochondrial matrix. Data
      indicated that HSP10 and HSP60 were inducible and functional in the Coilia nasus
      testis development and migration process, suggesting their essential roles in
      this process. The results also indicated that HSP60 may be one indicator of
      properly working mitochondrial import and refolding in the fish testis. This
      study also provides an expanded perspective on the role of heat shock protein
      families in spawning migration biology.

PMID- 28754008
TI  - Combination Therapy of PEG-HM-3 and Methotrexate Retards Adjuvant-Induced
      Arthritis.
AB  - At present, the early phenomenon of inflammatory angiogenesis is rarely studied
      in Rheumatoid arthritis (RA). Previous research found that PEG-HM-3, an integrin
      inhibitor, possessed anti-angiogenesis and anti-rheumatic activity. In this
      study, the advantages of inhibiting angiogenesis and immune cell adhesion and
      migration, as well as the benefits of anti-arthritis effects, were evaluated
      using a combination of PEG-HM-3 and methotrexate (MTX). In vitro, spleen cell
      proliferation and the levels of tumor necrosis factor alpha (TNF-alpha) in
      macrophage supernatant were assessed. Hind paw edema, arthritis index, clinical
      score, body weight and immunohistochemistry (IHC) of the spleen, thymus, and
      joint cavity were evaluated in vivo in adjuvant-induced arthritis rats. Joints of
      the left hind paws were imaged by X-ray. The expression of the toll-like receptor
      4 (TLR-4) protein was assessed in lipopolysaccharide (LPS)-induced synoviocytes.
      PEG-HM-3 combined with MTX significantly reduced primary and secondary swelling
      of the hind paws, the arthritis index, the clinical score and bone erosion. The
      results of IHC showed that the levels of interleukin-6 (IL-6) in spleens and the
      levels of TNF-alpha, CD31 (cluster of differentiation 31), and CD105 in the joint
      cavity were decreased. The body weight of rats was maintained during combination
      therapy. Ankle cavity integrity, and bone erosion and deformity were improved in
      combination treatment. The expression of TLR-4 was significantly reduced with
      combination treatment in rat synoviocytes. Co-suppression of both inflammation
      and angiogenesis in arthritis was achieved in this design with combination
      therapy. The activity of nuclear transcription factor (NF-kappaB) and the
      expression of inflammatory factors were down regulated via integrin alphavbeta3
      and TLR-4 signaling pathways. In the future, the application of this combination
      can be a candidate in early and mid-term RA therapy.

PMID- 28754009
TI  - Demonstration and Methodology of Structural Monitoring of Stringer Runs out
      Composite Areas by Embedded Optical Fiber Sensors and Connectors Integrated
      during Production in a Composite Plant.
AB  - Embedding optical fibers sensors into composite structures for Structural Health
      Monitoring purposes is not just one of the most attractive solutions contributing
      to smart structures, but also the optimum integration approach that insures
      maximum protection and integrity of the fibers. Nevertheless this intended
      integration level still remains an industrial challenge since today there is no
      mature integration process in composite plants matching all necessary
      requirements. This article describes the process developed to integrate optical
      fiber sensors in the Production cycle of a test specimen. The sensors, Bragg
      gratings, were integrated into the laminate during automatic tape lay-up and also
      by a secondary bonding process, both in the Airbus Composite Plant. The test
      specimen, completely representative of the root joint of the lower wing cover of
      a real aircraft, is comprised of a structural skin panel with the associated
      stringer run out. The ingress-egress was achieved through the precise design and
      integration of miniaturized optical connectors compatible with the manufacturing
      conditions and operational test requirements. After production, the specimen was
      trimmed, assembled and bolted to metallic plates to represent the real triform
      and buttstrap, and eventually installed into the structural test rig. The
      interrogation of the sensors proves the effectiveness of the integration process;
      the analysis of the strain results demonstrate the good correlation between fiber
      sensors and electrical gauges in those locations where they are installed nearby,
      and the curvature and load transfer analysis in the bolted stringer run out area
      enable demonstration of the consistency of the fiber sensors measurements. In
      conclusion, this work presents strong evidence of the performance of embedded
      optical sensors for structural health monitoring purposes, where in addition and
      most importantly, the fibers were integrated in a real production environment and
      the ingress-egress issue was solved by the design and integration of miniaturized
      connectors compatible with the manufacturing and structural test phases.

PMID- 28754010
TI  - Multiple Functions of D-alpha-Tocopherol Polyethylene Glycol 1000 Succinate
      (TPGS) as Curcumin Nanoparticle Stabilizer: In Vivo Kinetic Profile and Anti
      Ulcerative Colitis Analysis in Animal Model.
AB  - This study was conducted to evaluate the potential benefit of particle reduction
      down to nanoscale on curcumin, a unique natural active compound facing
      therapeutic problems due to low solubility and permeability. In addition, the
      presence of TPGS as a surfactant for multiple functions on curcumin nanoparticle
      was addressed. Observation was focused on bioavailability enhancement after oral
      administration and local anti-inflammatory improvement after rectal dosing.
      Nanonization of curcumin was performed using an up-scalable top down method.
      Specific animal models were used to study the in vivo kinetic profile and the
      biological activity of curcumin nanoparticle, compared with curcumin powder. d
      alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin
      nanoparticle was prepared through homogenization with high pressure of the 1500
      bar. An in vivo study was performed after oral administration of the preparations
      to male healthy Wistar rats, to monitor the plasma kinetic profile of curcumin.
      The biological activity study was conducted after rectal administration of the
      preparations in Wistar rats induced by 2,4,6-trinitrobenzene sulfonic acid to
      develop ulcerative colitis. The curcumin nanoparticle with a size of
      approximately 200 nm was successfully produced and revealed a better in vivo
      kinetic profile over the larger size of curcumin mixed with TPGS, with
      bioavailability (AUC0-infinity) that was accounted for seven-fold. In addition,
      the TPGS-stabilized curcumin nanoparticle demonstrated a superior local anti
      inflammatory effect in ulcerative colitis, indicated by the shifting of observed
      parameters close to the healthy status. The tremendously improved anti
      inflammatory effect of the TPGS-stabilized curcumin nanoparticle was found with a
      very low dose. Reducing the particle size of curcumin down to ~200 nm with the
      presence of TPGS seems to be a promising approach to improving the therapeutic
      value of curcumin.

PMID- 28754011
TI  - Student Perceptions and Acceptance of Mobile Technology in an Undergraduate
      Nursing Program.
AB  - Mobile technology allows healthcare students to access current evidence-based
      resources. The purpose of this study was to evaluate the student experience of
      implementing point-of-care (POC) smartphone applications in a first-semester
      undergraduate nursing program. Teaching methods included using case studies in
      the laboratory to familiarize students with the apps. At community screening
      sites, evidence-based guidelines were referenced when students discussed
      screening results with patients. Surveys were administered prior to implementing
      this innovation and after the students utilized the apps in direct patient
      interactions. Survey results were analyzed to evaluate student perceptions and
      acceptance of mobile technology. Students felt that healthcare smartphone apps
      were a helpful and convenient way to obtain evidence-based clinical information
      pertinent to direct care settings. Over 90% of students planned to continue using
      healthcare smartphone apps. In conclusion, healthcare smartphone apps are a way
      for students to become comfortable accessing evidence-based clinical resources.
      It is important to encourage students to use these resources early in the
      curriculum. Community screenings are an independent health promotion activity
      which assists in the attainment of health equity and fosters nursing leadership.

PMID- 28754012
TI  - Intra-Amniotic Administration (Gallus gallus) of Cicer arietinum and Lens
      culinaris Prebiotics Extracts and Duck Egg White Peptides Affects Calcium Status
      and Intestinal Functionality.
AB  - Calcium (Ca) is one of the most abundant inorganic elements in the human body and
      has many important physiological roles. Prebiotics and bioactive peptides are two
      important substances used to promote calcium uptake. However, the difference in
      mechanisms of the calcium uptake from these two supplements is not clear. By
      using the Gallus gallus model and the intra-amniotic administration procedure,
      the aim of this study was to investigate whether Ca status, intestinal
      functionality, and health-promoting bacterial populations were affected by
      prebiotics extracted from chickpea and lentil, and duck egg white peptides (DPs).
      Eleven groups (non-injected; 18 MOmega H2O; 4 mmol/L CaCl2; 50 mg/mL chickpea + 4
      mmol/L CaCl2; 50 mg/mL lentil + 4 mmol/L CaCl2; 40 mg/mL DPs + 4 mmol/L CaCl2; 5
      mg/mL Val-Ser-Glu-Glu (VSEE) + 4 mmol/L CaCl2; 50 mg/mL chickpea; 50 mg/mL
      lentil; 40 mg/mL DPs; 5 mg/mL VSEE) were utilized. Upon hatch, blood, cecum,
      small intestine, liver and bone were collected for assessment of serum bone
      alkaline phosphate level (BALP), the relative abundance of intestinal microflora,
      expression of Ca-related genes, brush border membrane (BBM) functional genes, and
      liver and bone mineral levels, respectively. The BALP level increased in the
      presence of lentil, DPs and VSEE (p < 0.05). The relative abundance of probiotics
      increased significantly (p < 0.05) by VSEE + Ca and chickpea. The expression of
      CalbindinD9k (Ca transporter) increased (p < 0.05) in Ca, chickpea + Ca and
      lentil + Ca groups. In addition, the brush border membrane functionality genes
      expressions increased (p < 0.05) by the chickpea or lentil extracts. Prebiotics
      and DPs beneficially affected the intestinal microflora and duodenal villus
      surface area. This research expands the understanding of the prebiotics'
      properties of chickpea and lentil extracts, and peptides' effects on calcium
      metabolism and gut health.

PMID- 28754013
TI  - Interference Effects Redress over Power-Efficient Wireless-Friendly Mesh Networks
      for Ubiquitous Sensor Communications across Smart Cities.
AB  - Ubiquitous sensing allows smart cities to take control of many parameters (e.g.,
      road traffic, air or noise pollution levels, etc.). An inexpensive Wireless Mesh
      Network can be used as an efficient way to transport sensed data. When that mesh
      is autonomously powered (e.g., solar powered), it constitutes an ideal portable
      network system which can be deployed when needed. Nevertheless, its power
      consumption must be restrained to extend its operational cycle and for preserving
      the environment. To this end, our strategy fosters wireless interface
      deactivation among nodes which do not participate in any route. As we show, this
      contributes to a significant power saving for the mesh. Furthermore, our strategy
      is wireless-friendly, meaning that it gives priority to deactivation of nodes
      receiving (and also causing) interferences from (to) the rest of the smart city.
      We also show that a routing protocol can adapt to this strategy in which certain
      nodes deactivate their own wireless interfaces.

PMID- 28754014
TI  - Through the Patients' Eyes: The Experience of End-Stage Renal Disease Patients
      Concerning the Provided Nursing Care.
AB  - Chronic kidney disease is a condition that affects both the physical and mental
      abilities of patients. Nursing care is of pivotal importance, in particular when
      end-stage renal disease (ESRD) patients are concerned, since the quality of the
      provided care may severely influence the patient's quality of life. This is why
      it is important to explore patient experiences concerning the rendered care.
      However, limited up-to-date studies have addressed this issue. The aim of the
      present study was to stress the experiences of ESRD patients concerning the
      provided nursing care in the hemodialysis unit at the University Hospital in
      Heraklion, Crete. A qualitative methodological approach was used, based on the
      principles of phenomenological epistemology. Semi-structured interviews were
      conducted, and open-ended questions were applied to record how patients
      experienced the rendered care during dialysis. The recorded data were analyzed
      via qualitative content analysis, which revealed three main themes: 'Physical
      Care', 'Psychological Support' and 'Education'. Patients' views were
      conceptualized into sub-themes within each main theme. The interviews revealed
      the varied and distinct views of ESRD patients, indicating that the rendered care
      should be individualized.

PMID- 28754015
TI  - Human Chorionic Gonadotropin and Breast Cancer.
AB  - Breast cancer is well known as a malignancy being strongly influenced by female
      steroids. Pregnancy is a protective factor against breast cancer. Human chorionic
      gonadotropin (HCG) is a candidate hormone which could mediate this antitumoral
      effect of pregnancy. For this review article, all original research articles on
      the role of HCG in breast cancer were considered, which are listed in PubMed
      database and were written in English. The role of HCG in breast cancer seems to
      be a paradox. Placental heterodimeric HCG acts as a protective agent by
      imprinting a permanent genomic signature of the mammary gland determining a
      refractory condition to malignant transformation which is characterized by
      cellular differentiation, apoptosis and growth inhibition. On the other hand,
      ectopic expression of beta-HCG in various cancer entities is associated with poor
      prognosis due to its tumor-promoting function. Placental HCG and ectopically
      expressed beta-HCG exert opposite effects on breast tumorigenesis. Therefore,
      mimicking pregnancy by treatment with HCG is suggested as a strategy for breast
      cancer prevention, whereas targeting beta-HCG expressing tumor cells seems to be
      an option for breast cancer therapy.

PMID- 28754016
TI  - Electrochemical Oxidation of EDTA in Nuclear Wastewater Using Platinum Supported
      on Activated Carbon Fibers.
AB  - A novel Pt/ACF (Pt supported on activated carbon fibers) electrode was
      successfully prepared with impregnation and electrodeposition method.
      Characterization of the electrodes indicated that the Pt/ACF electrode had a
      larger effective area and more active sites. Electrochemical degradation of
      ethylenediaminetetra-acetic acid (EDTA) in aqueous solution with Pt/ACF
      electrodes was investigated. The results showed that the 3% Pt/ACF electrode had
      a better effect on EDTA removal. The operational parameters influencing the
      electrochemical degradation of EDTA with 3% Pt/ACF electrode were optimized and
      the optimal removal of EDTA and chemical oxygen demand (COD) were 94% and 60%
      after 100 min on condition of the electrolyte concentration, initial
      concentration of EDTA, current density and initial value of pH were 0.1 mol/L,
      300 mg/L, 40 mA/cm2 and 5.0, respectively. The degradation intermediates of EDTA
      in electrochemical oxidation with 3% Pt/ACF electrode were identified by gas
      chromatography-mass spectrum (GC-MS).

PMID- 28754017
TI  - Development and Validation of a Behavioural Index for Adaptation to High Summer
      Temperatures among Urban Dwellers.
AB  - One of the consequences of climate change is the growing number of extreme
      weather events, including heat waves, which have substantial impacts on the
      health of populations. From a public health standpoint, it is vital to ensure
      that people can adapt to high heat, particularly in cities where heat islands
      abound. Identifying indicators to include in a parsimonious index would help
      better differentiate individuals who adapt well to heat from those who do not
      adapt as well. This study aimed at developing and validating a summer heat
      adaptation index for residents of the 10 largest cities in the province of
      Quebec, Canada. A sample of 2000 adults in 2015 and 1030 adults in 2016 completed
      a telephone questionnaire addressing their adoption (or non-adoption) of
      behaviours recommended by public health agencies to protect themselves during
      periods of high temperature, and their perceptions of how high summer heat
      affects their mental and physical health. Item analysis, confirmatory factor
      analysis, multiple correspondence analysis, measurement invariance analyses and
      criterion-validity analyses were used to develop a 12-behaviour heat adaptation
      index for distinguishing between individuals who adapt well to high temperatures
      and those who do not adapt as well. The results indicated that the measurement
      and the factor structure of the index were invariant (equivalent) across the two
      independent samples of participants who completed the questionnaire at different
      times one year apart, an important prerequisite for unambiguous interpretation of
      index scores across groups and over time. The results also showed that
      individuals who perceived more adverse effects on their physical or mental health
      adopted more preventive behaviours during periods of high temperatures and
      humidity conditions compared to those who felt lesser or no effects. This study
      thus presents support for the validity of the index that could be used in future
      studies to monitor preventive behaviours adoption during summer periods of high
      temperature.

PMID- 28754018
TI  - Investigating the Influence of Magnesium Ions on p53-DNA Binding Using Atomic
      Force Microscopy.
AB  - p53 is a tumor suppressor protein that plays a significant role in apoptosis and
      senescence, preserving genomic stability, and preventing oncogene expression.
      Metal ions, such as magnesium and zinc ions, have important influences on p53-DNA
      interactions for stabilizing the structure of the protein and enhancing its
      affinity to DNA. In the present study, we systematically investigated the
      interaction of full length human protein p53 with DNA in metal ion solution by
      atomic force microscopy (AFM). The p53-DNA complexes at various p53
      concentrations were scanned by AFM and their images are used to measure the
      dissociation constant of p53-DNA binding by a statistical method. We found that
      the dissociation constant of p53 binding DNA is 328.02 nmol/L in physiological
      buffer conditions. The influence of magnesium ions on p53-DNA binding was studied
      by AFM at various ion strengths through visualization. We found that magnesium
      ions significantly stimulate the binding of the protein to DNA in a sequence
      independent manner, different from that stimulated by zinc. Furthermore, the high
      concentrations of magnesium ions can promote p53 aggregation and even lead to the
      formation of self-assembly networks of DNA and p53 proteins. We propose an
      aggregation and self-assembly model based on the present observation and discuss
      its biological meaning.

PMID- 28754019
TI  - Effects of K11R and G31P Mutations on the Structure and Biological Activities of
      CXCL8: Solution Structure of Human CXCL8(3-72)K11R/G31P.
AB  - The ELR-CXC chemokines are important to neutrophil inflammation in many acute and
      chronic diseases. Among them, CXCL8 (interleukin-8, IL-8), the expression levels
      of which are elevated in many inflammatory diseases, binds to both the CXCR1 and
      CXCR2 receptors with high affinity. Recently, an analogue of human CXCL8, CXCL8(3
      72)K11R/G31P (hG31P) has been developed. It has been demonstrated that hG31P is a
      high affinity antagonist for both the CXCR1 and CXCR2. Herein, we have determined
      the solution structure and the CXCR1 N-terminal peptide binding sites of hG31P by
      NMR spectroscopy. We have found that the displacement within the tertiary
      structure of the 30 s loop and the N-terminal region and more specifically change
      of the loop conformation (especially H33), of hG31P may affect its binding to the
      CXCR1 receptor and thereby inhibit human neutrophil chemotactic responses induced
      by ELR-CXC chemokines. Our results provide a structural basis for future clinical
      investigations of this CXCR1/CXCR2 receptor antagonist and for the further
      development of CXCL8 based antagonists.

PMID- 28754020
TI  - In Situ beta-Glucan Fortification of Cereal-Based Matrices by Pediococcus
      parvulus 2.6: Technological Aspects and Prebiotic Potential.
AB  - Bacterial exopolysaccharides produced by lactic acid bacteria are of increasing
      interest in the food industry, since they might enhance the technological and
      functional properties of some edible matrices. In this work, Pediococcus parvulus
      2.6, which produces an O2-substituted (1,3)-beta-d-glucan exopolysaccharide only
      synthesised by bacteria, was proposed as a starter culture for the production of
      three cereal-based fermented foods. The obtained fermented matrices were
      naturally bio-fortified in microbial beta-glucans, and used to investigate the
      prebiotic potential of the bacterial exopolysaccharide by analysing the impact on
      the survival of a probiotic Lactobacillus plantarum strain under starvation and
      gastrointestinal simulated conditions. All of the assays were performed by using
      as control of the P. parvulus 2.6's performance, the isogenic beta-glucan non
      producing 2.6NR strain. Our results showed a differential capability of P.
      parvulus to ferment the cereal flours. During the fermentation step, the beta
      glucans produced were specifically quantified and their concentration correlated
      with an increased viscosity of the products. The survival of the model probiotic
      L. plantarum WCFS1 was improved by the presence of the bacterial beta-glucans in
      oat and rice fermented foods under starvation conditions. The probiotic bacteria
      showed a significantly higher viability when submitted to a simulated intestinal
      stress in the oat matrix fermented by the 2.6 strain. Therefore, the cereal
      flours were a suitable substrate for in situ bio-fortification with the bacterial
      beta-glucan, and these matrices could be used as carriers to enhance the
      beneficial properties of probiotic bacteria.

PMID- 28754021
TI  - DNA Damage Tolerance by Eukaryotic DNA Polymerase and Primase PrimPol.
AB  - PrimPol is a human deoxyribonucleic acid (DNA) polymerase that also possesses
      primase activity and is involved in DNA damage tolerance, the prevention of
      genome instability and mitochondrial DNA maintenance. In this review, we focus on
      recent advances in biochemical and crystallographic studies of PrimPol, as well
      as in identification of new protein-protein interaction partners. Furthermore, we
      discuss the possible functions of PrimPol in both the nucleus and the
      mitochondria.

PMID- 28754023
TI  - Dissipation and Residues of Pyrethrins in Leaf Lettuce under Greenhouse and Open
      Field Conditions.
AB  - Pyrethrins are nowadays widely used for prevention and control of insects in leaf
      lettuce. However, there is a concern about the pesticide residue in leaf lettuce.
      A reliable analytical method for determination of pyrethrins (pyrethrin-and P,
      cinerin I and P, and jasmolin I and P) in leaf lettuce was developed by using gas
      chromatography-mass spectrometry (GC-MS). Recoveries of pyrethrins in leaf
      lettuce at three spiking levels were 99.4-104.0% with relative standard
      deviations of 0.9-3.1% (n = 5). Evaluation of dissipation and final residues of
      pyrethrins in leaf lettuce were determined at six different locations, including
      the open field, as well as under greenhouse conditions. The initial concentration
      of pyrethrins in greenhouse (0.57 mg/kg) was higher than in open field (0.25
      mg/kg) and the half-life for pyrethrins disappearance in field lettuce (0.7 days)
      was less than that greenhouse lettuce (1.1 days). Factors such as rainfall, solar
      radiation, wind speed, and crop growth rate are likely to have caused these
      results. The final residue in leaf lettuce was far below the maximum residue
      limits (MRLs) (1 mg/kg established by the European Union (EU), Australia, Korea,
      Japan).

PMID- 28754022
TI  - Unfolding Novel Mechanisms of Polyphenol Flavonoids for Better Glycaemic Control:
      Targeting Pancreatic Islet Amyloid Polypeptide (IAPP).
AB  - Type 2 diabetes (T2D) is characterised by hyperglycaemia resulting from defective
      insulin secretion, insulin resistance, or both. The impact of over-nutrition and
      reduced physical activity, evidenced by the exponential rise in obesity and the
      prevalence of T2D, strongly supports the implementation of lifestyle modification
      programs. Accordingly, an increased consumption of fruits and plant-derived foods
      has been advocated, as their intake is inversely correlated with T2D prevalence;
      this has been attributed, in part, to their contained polyphenolic compounds.
      Over the last decade, a body of work has focussed on establishing the mechanisms
      by which polyphenolic compounds exert beneficial effects to limit carbohydrate
      digestion, enhance insulin-mediated glucose uptake, down-regulate hepatic
      gluconeogenesis and decrease oxidative stress; the latter anti-oxidative property
      being the most documented. Novel effects on the inhibition of glucocorticoid
      action and the suppression of amylin misfolding and aggregation have been
      identified more recently. Amyloid fibrils form from spontaneously misfolded
      amylin, depositing in islet cells to elicit apoptosis, beta cell degeneration and
      decrease insulin secretion, with amyloidosis affecting up to 80% of pancreatic
      islet cells in T2D. Therefore, intervening with polyphenolic compounds offers a
      novel approach to suppressing risk or progression to T2D. This review gives an
      update on the emerging mechanisms related to dietary polyphenol intake for the
      maintenance of glycaemic control and the prevention of T2D.

PMID- 28754025
TI  - Aquatic Insects and their Potential to Contribute to the Diet of the Globally
      Expanding Human Population.
AB  - Of the 30 extant orders of true insect, 12 are considered to be aquatic, or
      semiaquatic, in either some or all of their life stages. Out of these, six orders
      contain species engaged in entomophagy, but very few are being harvested
      effectively, leading to over-exploitation and local extinction. Examples of
      existing practices are given, ranging from the extremes of including insects
      (e.g., dipterans) in the dietary cores of many indigenous peoples to consumption
      of selected insects, by a wealthy few, as novelty food (e.g., caddisflies). The
      comparative nutritional worth of aquatic insects to the human diet and to
      domestic animal feed is examined. Questions are raised as to whether natural
      populations of aquatic insects can yield sufficient biomass to be of practicable
      and sustained use, whether some species can be brought into high-yield
      cultivation, and what are the requirements and limitations involved in achieving
      this?

PMID- 28754026
TI  - Iron Bioavailability Studies of the First Generation of Iron-Biofortified Beans
      Released in Rwanda.
AB  - This paper represents a series of in vitro iron (Fe) bioavailability experiments,
      Fe content analysis and polyphenolic profile of the first generation of Fe
      biofortified beans (Phaseolus vulgaris) selected for human trials in Rwanda and
      released to farmers of that region. The objective of the present study was to
      demonstrate how the Caco-2 cell bioassay for Fe bioavailability can be utilized
      to assess the nutritional quality of Fe in such varieties and how they may
      interact with diets and meal plans of experimental studies. Furthermore,
      experiments were also conducted to directly compare this in vitro approach with
      specific human absorption studies of these Fe biofortified beans. The results
      show that other foods consumed with beans, such as rice, can negatively affect Fe
      bioavailability whereas potato may enhance the Fe absorption when consumed with
      beans. The results also suggest that the extrinsic labelling approach to
      measuring human Fe absorption can be flawed and thus provide misleading
      information. Overall, the results provide evidence that the Caco-2 cell bioassay
      represents an effective approach to evaluate the nutritional quality of Fe
      biofortified beans, both separate from and within a targeted diet or meal plan.

PMID- 28754027
TI  - Illuminating the Psychological Experience of Elderly Loneliness from a Societal
      Perspective: A Qualitative Study of Alienation between Older People and Society.
AB  - Loneliness is a common experience among older people that is associated with
      health risks and negative well-being. As a psychological phenomenon, it has
      typically been defined in Western research literature as the discrepancy between
      desired and actual interpersonal relations. In our qualitative study in Hong
      Kong, we offer insight into ageing and loneliness in an urban environment of the
      non-Western world and propose to reconceptualise loneliness by exploring older
      people's experience of alienation at the societal level as an important but often
      neglected dimension of their loneliness. Thirty-seven community-dwelling, Chinese
      adults aged 65 and above were interviewed in focus groups and their accounts
      analysed and interpreted using a phenomenological approach. Findings revealed
      that focus group participants perceived insufficient care for older people, a
      growing distance between themselves and society, and their disintegrating
      identity in society to be primary sources of societal alienation. In response,
      older people adopted a more passive lifestyle, attributed marginalisation and
      inequality to old age, and developed negative feelings including unease towards
      ageing, vulnerability and helplessness, and anger. The emergence of these key
      components and underlying themes of societal alienation illuminated neglected
      facets of the psychological phenomenon of loneliness and highlighted new
      implications for policy, practice, and research from a societal perspective to
      address older people's loneliness in urban settings.

PMID- 28754024
TI  - A Comprehensive Review of Common Bacterial, Parasitic and Viral Zoonoses at the
      Human-Animal Interface in Egypt.
AB  - Egypt has a unique geographical location connecting the three old-world
      continents Africa, Asia and Europe. It is the country with the highest population
      density in the Middle East, Northern Africa and the Mediterranean basin. This
      review summarizes the prevalence, reservoirs, sources of human infection and
      control regimes of common bacterial, parasitic and viral zoonoses in animals and
      humans in Egypt. There is a gap of knowledge conerning the epidemiology of
      zoonotic diseases at the human-animal interface in different localities in Egypt.
      Some zoonotic agents are "exotic" for Egypt (e.g., MERS-CoV and Crimean-Congo
      hemorrhagic fever virus), others are endemic (e.g., Brucellosis, Schistosomiasis
      and Avian influenza). Transboundary transmission of emerging pathogens from and
      to Egypt occurred via different routes, mainly importation/exportation of
      apparently healthy animals or migratory birds. Control of the infectious agents
      and multidrug resistant bacteria in the veterinary sector is on the frontline for
      infection control in humans. The implementation of control programs significantly
      decreased the prevalence of some zoonoses, such as schistosomiasis and
      fascioliasis, in some localities within the country. Sustainable awareness,
      education and training targeting groups at high risk (veterinarians, farmers,
      abattoir workers, nurses, etc.) are important to lessen the burden of zoonotic
      diseases among Egyptians. There is an urgent need for collaborative surveillance
      and intervention plans for the control of these diseases in Egypt.

PMID- 28754028
TI  - 4SM: A Novel Self-Calibrated Algebraic Ratio Method for Satellite-Derived
      Bathymetry and Water Column Correction.
AB  - All empirical water column correction methods have consistently been reported to
      require existing depth sounding data for the purpose of calibrating a simple
      depth retrieval model; they yield poor results over very bright or very dark
      bottoms. In contrast, we set out to (i) use only the relative radiance data in
      the image along with published data, and several new assumptions; (ii) in order
      to specify and operate the simplified radiative transfer equation (RTE); (iii)
      for the purpose of retrieving both the satellite derived bathymetry (SDB) and the
      water column corrected spectral reflectance over shallow seabeds. Sea truth
      regressions show that SDB depths retrieved by the method only need tide
      correction. Therefore it shall be demonstrated that, under such new assumptions,
      there is no need for (i) formal atmospheric correction; (ii) conversion of
      relative radiance into calibrated reflectance; or (iii) existing depth sounding
      data, to specify the simplified RTE and produce both SDB and spectral water
      column corrected radiance ready for bottom typing. Moreover, the use of the
      panchromatic band for that purpose is introduced. Altogether, we named this
      process the Self-Calibrated Supervised Spectral Shallow-sea Modeler (4SM). This
      approach requires a trained practitioner, though, to produce its results within
      hours of downloading the raw image. The ideal raw image should be a "near-nadir"
      view, exhibit homogeneous atmosphere and water column, include some coverage of
      optically deep waters and bare land, and lend itself to quality removal of haze,
      atmospheric adjacency effect, and sun/sky glint.

PMID- 28754029
TI  - Land Use and Land Cover Change in the Qinghai Lake Region of the Tibetan Plateau
      and Its Impact on Ecosystem Services.
AB  - Exploration of land use and land cover change (LULCC) and its impacts on
      ecosystem services in Tibetan plateau is valuable for landscape and environmental
      conservation. In this study, we conduct spatial analysis on empirical land use
      and land cover data in the Qinghai Lake region for 1990, 2000, and 2010 and
      simulate land cover patterns for 2020. We then evaluate the impacts of LULCC on
      ecosystem service value (ESV), and analyze the sensitivity of ESV to LULCC to
      identify the ecologically sensitive area. Our results indicate that, from 1990 to
      2010, the area of forest and grassland increased while the area of unused land
      decreased. Simulation results suggest that the area of grassland and forest will
      continue to increase and the area of cropland and unused land will decrease for
      2010-2020. The ESV in the study area increased from 694.50 billion Yuan in 1990
      to 714.28 billion Yuan in 2000, and to 696.72 billion Yuan in 2020. Hydrology
      regulation and waste treatment are the top two ecosystem services in this region.
      The towns surrounding the Qinghai Lake have high ESVs, especially in the north of
      the Qinghai Lake. The towns with high ESV sensitivity to LULCC are located in the
      northwest, while the towns in the north of the Qinghai Lake experienced
      substantial increase in sensitivity index from 2000-2010 to 2010-2020, especially
      for three regulation services and aesthetic landscape provision services.

PMID- 28754030
TI  - Growth Mechanism Studies of ZnO Nanowires: Experimental Observations and Short
      Circuit Diffusion Analysis.
AB  - Plenty of studies have been performed to probe the diverse properties of ZnO
      nanowires, but only a few have focused on the physical properties of a single
      nanowire since analyzing the growth mechanism along a single nanowire is
      difficult. In this study, a single ZnO nanowire was synthesized using a Ti
      assisted chemical vapor deposition (CVD) method to avoid the appearance of
      catalytic contamination. Two-dimensional energy dispersive spectroscopy (EDS)
      mapping with a diffusion model was used to obtain the diffusion length and the
      activation energy ratio. The ratio value is close to 0.3, revealing that the
      growth of ZnO nanowires was attributed to the short-circuit diffusion.

PMID- 28754031
TI  - Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards
      MAPK Signaling.
AB  - Protein-protein interactions play a pivotal role in normal cellular functions as
      well as in carcinogenesis. The protein-protein interactions form functional
      clusters during signal transduction. To elucidate the fine calibration of the
      protein-protein interactions of protein tyrosine phosphatase interacting protein
      51 (PTPIP51) a small molecule drug, namely LDC-3, directly targeting PTPIP51 is
      now available. Therefore, LDC-3 allows for the studying of the regulation of the
      endogenous interactome by modulating PTPIP51 binding capacity. Small interfering
      ribonucleic acid (siRNA) experiments show that the modification in PTPIP51
      binding capacity is induced by LDC-3. Application of LDC-3 annuls the known
      regulatory phosphorylation mechanisms for PTPIP51 and consequently, significantly
      alters the assembly of the PTPIP51 associated protein complexes. The treatment of
      human keratinocytes (HaCaT cells) with LDC-3 induces an altered protein-protein
      interaction profile of the endogenous interactome of PTPIP51. In addition, LDC-3
      stabilizes PTPIP51 within a mitogen activated protein kinase (MAPK) complex
      composed of Raf-1 and the scaffold protein 14-3-3, independent of the
      phosphorylation status of PTPIP51. Of note, under LDC-3 treatment the regulatory
      function of the PTP1B on PTPIP51 fails to impact the PTPIP51 interaction
      characteristics, as reported for the HaCaT cell line. In summary, LDC-3 gives the
      unique opportunity to directly modulate PTPIP51 in malignant cells, thus
      targeting potential dysregulated signal transduction pathways such as the MAPK
      cascade. The provided data give critical insights in the therapeutic potential of
      PTPIP51 protein interactions and thus are basic for possible targeted therapy
      regimens.

PMID- 28754032
TI  - Spectrum Effect Relationship and Component Knock-Out in Angelica Dahurica Radix
      by High Performance Liquid Chromatography-Q Exactive Hybrid Quadrupole-Orbitrap
      Mass Spectrometer.
AB  - Different extracts of Angelica dahuricae were available for whitening or treating
      vitiligo clinically. They showed inhibitory or activating effects on tyrosinase,
      a rate-limiting enzyme of melanogenesis. This study aimed to identify active
      compounds on tyrosinase in water extract of Angelica dahurica Radix. We applied
      spectrum-effect relationship and component knock-out methods to make it clear.
      HPLC was used to obtain the specific chromatograms. The effects on tyrosinase
      activity were examined by measuring the oxidation rate of levodopa in vitro.
      Partial least squares method was used to examine the spectrum-effect
      relationships. The knocked-out samples were prepared by HPLC method, and the
      identification of knocked-out compounds was conducted by the high performance
      liquid chromatography-four stage rod-electrostatic field orbit trap high
      resolution mass spectrometry. Results showed that S6, S14, S18, S21, S35, S36,
      S37, S40, and S41 were positively correlated to inhibitory activity of Angelica
      dahuricae on tyrosinase whereas S9, S11, S8, S12, S22, and S30 were negatively
      correlated. When the concentration of each sample was 1 g.mL-1, equal to the
      amount of raw medicinal herbs, oxypeucedanin hydrate, imperatorin, cnidilin, and
      isoimperatorin had inhibitory effects on tyrosinase activity whereas
      byakangelicin and bergapten had activating effects.

PMID- 28754033
TI  - The Influence of Glycosylation of Natural and Synthetic Prenylated Flavonoids on
      Binding to Human Serum Albumin and Inhibition of Cyclooxygenases COX-1 and COX-2.
AB  - The synthesis of different classes of prenylated aglycones (alpha,beta
      dihydroxanthohumol (2) and (Z)-6,4'-dihydroxy-4-methoxy-7-prenylaurone (3)) was
      performed in one step reactions from xanthohumol (1)-major prenylated chalcone
      naturally occurring in hops. Obtained flavonoids (2-3) and xanthohumol (1) were
      used as substrates for regioselective fungal glycosylation catalyzed by two
      Absidia species and Beauveria bassiana. As a result six glycosides (4-9) were
      formed, of which four glycosides (6-9) have not been published so far. The
      influence of flavonoid skeleton and the presence of glucopyranose and 4-O
      methylglucopyranose moiety in flavonoid molecule on binding to main protein in
      plasma, human serum albumin (HSA), and inhibition of cyclooxygenases COX-1 and
      COX-2 were investigated. Results showed that chalcone (1) had the highest binding
      affinity to HSA (8.624 * 104 M-1) of all tested compounds. It has also exhibited
      the highest inhibition of cyclooxygenases activity, and it was a two-fold
      stronger inhibitor than alpha,beta-dihydrochalcone (2) and aurone (3). The
      presence of sugar moiety in flavonoid molecule caused the loss of HSA binding
      activity as well as the decrease in inhibition of cyclooxygenases activity.

PMID- 28754034
TI  - Effect of cultivation pH on the surface hydrophobicity of Bacillus subtilis
      spores.
AB  - Bacillus subtilis spores are often used as biological indicators (BI) to monitor
      decontamination processes with gaseous hydrogen peroxide. Results in practical
      inactivation validation tests, however, vary considerably with no available
      explanation so far. This study reports on the effect of cultivation pH on spore
      surface hydrophobicity. Surface hydrophobicity is suspected to have an impact on
      the decontamination of technical surfaces such as packaging material when
      gaseous, condensing hydrogen peroxide is applied. It is the aim of this study to
      examine the impact of different cultivation pH levels on surface hydrophobicity
      and resistance of B. subtilis spores. Submersed cultivation of B. subtilis in
      bioreactors at controlled conditions with different static pH levels led to
      contact angles ranged between 50 degrees  and 80 degrees , which was analyzed
      with water on a homogeneous layer of spores on a filter sheet. Resistance of
      spores was also affected by the cultivation pH. The results show that the
      culturing conditions during BI production should be controlled to obtain BI with
      specified characteristics in inactivation validation tests.

PMID- 28754035
TI  - Erratum to: Investigations of Heavy Metal Ion Sorption Using Nanocomposites of
      Iron-Modified Biochar.

PMID- 28754036
TI  - Influence of Water on the Structure and Dielectric Properties of the
      Microcrystalline and Nano-Cellulose.
AB  - Influence of water in the different states on a structure and dielectric
      properties of microcrystalline cellulose were studied by of X-ray,
      thermogravimetry, and dielectric spectroscopy. At research of microcrystalline
      cellulose (MCC) with different content of water, it is shown that the molecules
      of water are located in the macropores of MCC and in multimolecular hydrated
      layers. It is shown that at the increase of concentration of water in a hydrated
      shell, the reorganization of molecules of cellulose in the surface of
      crystallites takes place, and as a result, their transversal size and
      crystallinity increase. It is shown that during the concentration of water, more
      than 13% in a continuous hydrated shell of crystallites appears. Temperature
      dependences of actual and imaginary parts of complex dielectric permittivity were
      studied in the interval of temperatures [-180 / 120]  degrees C on frequencies of
      f = 5, 10, 20, and 50 kHz. A low-temperature relaxation process and high
      temperature transition were observed. Low-temperature relaxation process which is
      related to transition of surface methylol groups of molecules of cellulose
      conformation from tg to tt is shifted toward low temperatures at the increase of
      concentration of water in microcrystalline cellulose.

PMID- 28754037
TI  - High-Throughput Fabrication of Quality Nanofibers Using a Modified Free Surface
      Electrospinning.
AB  - Based on bubble electrospinning (BE), a modified free surface electrospinning
      (MFSE) using a cone-shaped air nozzle combined with a solution reservoir made of
      copper tubes was presented to increase the production of quality nanofibers. In
      the MFSE process, sodium dodecyl benzene sulfonates (SDBS) were added in the
      electrospun solution to generate bubbles on a liquid surface. The effects of
      applied voltage and generated bubbles on the morphology and production of
      nanofibers were investigated experimentally and theoretically. The theoretical
      analysis results of the electric field were in good agreement with the
      experimental data and showed that the quality and production of nanofibers were
      improved with the increase of applied voltage, and the generated bubbles would
      decrease the quality and production of nanofibers.

PMID- 28754038
TI  - Two-step deposition of Al-doped ZnO on p-GaN to form ohmic contacts.
AB  - Al-doped ZnO (AZO) thin films were deposited directly on p-GaN substrates by
      using a two-step deposition consisting of polymer assisted deposition (PAD) and
      atomic layer deposition (ALD) methods. Ohmic contacts of the AZO on p-GaN have
      been formed. The lowest sheet resistance of the two-step prepared AZO films
      reached to 145 Omega/sq, and the specific contact resistance reduced to 1.47 * 10
      2 Omega.cm2. Transmittance of the AZO films remained above 80% in the visible
      region. The combination of PAD and ALD technique can be used to prepare p-type
      ohmic contacts for optoelectronics.

PMID- 28754039
TI  - Nanodiamond-chymotrypsin and nanodiamond-papain conjugates, their synthesis and
      activity and visualization of their interaction with cells using optical and
      electron microscopy.
AB  - Two novel conjugates of detonation nanodiamonds (dNDs) with the proteolytic
      enzymes chymotrypsin and papain were synthesized. The synthesis was performed via
      functionalization of the dNDs' surface with acidic/alkali treatment followed by
      carbodiimide-mediated protein binding. Covalent binding of the enzymes was
      confirmed by Fourier transform infrared spectrographic analysis and high
      performance liquid chromatography (HPLC) amino acid analysis. HPLC also proved
      the preservation of the enzymes' composition during synthesis. The same assay was
      used to determine the binding ratios. The ratios were 12% (mass to mass) for
      chymotrypsin and 7.4% for papain. The enzymatic activity of the conjugates was
      measured using chromogenic substrates and appeared to be approximately 40% of
      that of the native enzymes. The optimum pH values and stability under various
      conditions were determined. The sizes of resulting particles were measured using
      dynamic light scattering and direct electron microscopic observation. The enzyme
      conjugates were shown to be prone to aggregation, resulting in micrometer-sized
      particles. The zeta-potentials were measured and found to be positive for the
      conjugates. The conjugated enzymes were tested for biological activity using an
      in vitro model of cultured transformed human epithelial cells (HeLa cell line).
      It was shown that dND-conjugated enzymes effectively bind to the surface of the
      cells and that enzymes attack exposed proteins on the plasma membrane, including
      cell adhesion molecules. Incubation with conjugated enzymes results in
      morphological changes of the cells but does not affect cell viability, as judged
      by monitoring the cell division index and conducting ultrastructural studies.
      dNDs are internalized by the cells via endocytosis, being enclosed in forming
      coated vesicles by chance, and they accumulate in single membrane-bound vacuoles,
      presumably late endosomes/phagosomes, along with multimembranous onionlike
      structures. The authors propose a model of a stepwise conjugate binding to the
      cell membrane and gradual release of the enzymes.

PMID- 28754040
TI  - The growing challenge of dementia and its impact on patients, their caregivers,
      and providers.

PMID- 28754042
TI  - Dying with dementia-how can we improve the care and support of patients and their
      families.

PMID- 28754043
TI  - Care staff perspective on use of texture modified food in care home residents
      with dysphagia and dementia.
AB  - BACKGROUND: Dysphagia and dementia are conditions, which combined, can lead to
      complications for the person and require good nutritional care. There is very
      little evidence-based literature regarding nutritional care for people with
      dysphagia and dementia. It is clear that care staff plays a vital role, and that
      communication and informed decision-making are critical to the process, yet
      little is known regarding the use of available interventions such as texture
      modified food (TMF), and their acceptability and feasibility for care staff and
      residents. Therefore the aim of this study was to investigate the experiences of
      care staff when providing nutritional care for people with dysphagia and
      dementia, and their impressions and experience of using TMF as a new intervention
      for nutrition. METHODS: This was a qualitative study with an inductive approach,
      which aimed to explore the experience of care staff using TMF in a care home
      setting. Data were collected using focus group interviews, an approach which is
      validated as a means of supporting and developing the understanding of a
      phenomenon, through interactions and discussions in the group. Participants were
      care staff working in a care home setting in Norway. RESULTS: Twelve participants
      were recruited to this study across two focus groups. The cohort included four
      nurses, six practical nurses, one nurse assistants and one student nurse. Four
      main categories emerged from the focus group discussions regarding the use of
      TMF. These were: (I) emotional strain; (II) deficient nutritional care; (III)
      increased self-efficacy with use of TMF; (IV) better nutritional care with TMF.
      CONCLUSIONS: Use of TMF to improve nutritional care for people with dysphagia
      appears to have merit for both residents and care staff, and should be considered
      as a means of improving nutritional care for people with dementia in care homes.
      Minimizing feeding difficulties and increasing nutritional intake is an important
      goal when caring for this vulnerable group of people, and there is a need to
      provide better training and support for care staff to ensure they feel confident
      and empowered to provide high quality nutritional care. The existing Norwegian
      Directorate of Health checklist for nutritional care may provide a helpful basis
      for improvements to guidance that accounts for the needs of staff and
      institutions. Further research and evaluation of an intervention for tailored
      nutritional care is warranted to improve this critical aspect of dementia care.

PMID- 28754044
TI  - Relational approach to ethics and quality improvement in institutional care for
      people with dementia.
AB  - BACKGROUND: Autonomy has become a key organizing principle in the official and
      expert discourses of the social services focused on strengthening of clients'
      independence and self-sufficiency. While "caring" has been seen as a threat to
      the autonomy of an individual, the care dependency and need for palliative care
      for people with dementia living in residential institutions are growing. METHODS:
      Participatory action research was realized in 9 homes providing services for
      people with dementia with the aim to improve the quality of care. Research teams
      from the homes were involved in assisted self-assessment which included
      observation, documentation analysis, workshops, interviews and interventions
      targeting the issues arising from practice. Ethnographic research was performed
      by the consultant/researcher to reflect on the experience. RESULTS: Over the last
      15 years, the needs of clients in the residential care institutions in the Czech
      Republic have changed significantly and the pressure on people involved in direct
      care is growing. I suggest that relational approach to care, enhancing personal
      commitment of care workers and their appreciation of sociomateriality of caring
      relations, is well suited for enacting autonomy and dignity of people living and
      dying with dementia. The relational approach to care improvement is embedded in
      everyday practices and thus brings a wider scope of possibilities for providing
      good care than the controlling mode of improvement, measuring evidence against
      the national standards. CONCLUSIONS: If we are, as a collective, to build up
      appropriate structures and resources in dementia care, more attention must be
      paid to the needs of residents and care workers alike, as well as to realities of
      the daily practices.

PMID- 28754045
TI  - Implementing the Namaste Care Program for residents with advanced dementia:
      exploring the perceptions of families and staff in UK care homes.
AB  - BACKGROUND: Increasing numbers of older people with advanced dementia are cared
      for in care homes. No cure is available, so research focused on improving quality
      of life and quality of care for people with dementia is needed to support them to
      live and die well. The Namaste Care programme is a multi-dimensional care program
      with sensory, psycho-social and spiritual components intended to enhance quality
      of life and quality of care for people with advanced dementia. The aim of the
      study was to establish whether the Namaste Care program can be implemented in UK
      care homes; and what effect Namaste Care has on the quality of life of residents
      with advanced dementia, their families and staff. This article explores the
      qualitative findings of the study, reporting the effect of the programme on the
      families of people with advanced dementia and care home staff, and presenting
      their perceptions of change in care. METHODS: An organisational action research
      methodology was used. Focus groups and interviews were undertaken pre/post
      implementation of the Namaste Care program. The researcher kept a reflective
      diary recording data on the process of change. A comments book was available to
      staff and relatives in each care home. Data was analysed thematically within each
      care home and then across all care homes. RESULTS: Six care homes were recruited
      in south London: one withdrew before the study was underway. Of the five
      remaining care homes, four achieved a full Namaste Care program. One care home
      did not achieve the full program during the study, and another discontinued
      Namaste Care when the study ended. Every home experienced management disruption
      during the study. Namaste Care challenged normal routinised care for older people
      with advanced dementia. The characteristics of care uncovered before Namaste was
      implemented were: chaos and confusion, rushing around, lack of trust, and
      rewarding care. After the programme was implemented these perceptions were
      transformed, and themes of calmness, reaching out to each other, seeing the
      person, and, enhanced well-being, emerged. CONCLUSIONS: Namaste Care can enrich
      the quality of life of older people with advanced dementia in care homes. The
      program was welcomed by care home staff and families, and was achieved with only
      modest expenditure and no change in staffing levels. The positive impact on
      residents quality of life influenced the well-being of family carers. Care staff
      found the changes in care enjoyable and rewarding. Namaste Care was valued for
      the benefits seen in residents; the improvement in relationships; and the shift
      towards a person-centred, relationship-based culture of care brought about by
      introducing the program. Namaste Care deserves further exploration and
      investigation including a randomised controlled trial.

PMID- 28754046
TI  - Using the ecological framework to identify barriers and enablers to implementing
      Namaste Care in Canada's long-term care system.
AB  - BACKGROUND: Higher acuity of care at the time of admission to long-term care
      (LTC) is resulting in a shorter period to time of death, yet most LTC homes in
      Canada do not have formalized approaches to palliative care. Namaste Care is a
      palliative care approach specifically tailored to persons with advanced cognitive
      impairment who are living in LTC. The purpose of this study was to employ the
      ecological framework to identify barriers and enablers to an implementation of
      Namaste Care. METHODS: Six group interviews were conducted with families,
      unlicensed staff, and licensed staff at two Canadian LTC homes that were planning
      to implement Namaste Care. None of the interviewees had prior experience
      implementing Namaste Care. The resulting qualitative data were analyzed using a
      template organizing approach. RESULTS: We found that the strongest implementation
      enablers were positive perceptions of need for the program, benefits of the
      program, and fit within a resident-centred or palliative approach to care.
      Barriers included a generally low resource base for LTC, the need to adjust
      highly developed routines to accommodate the program, and reliance on a casual
      work force. CONCLUSIONS: We conclude that within the Canadian LTC system,
      positive perceptions of Namaste Care are tempered by concerns about
      organizational capacity to support new programming.

PMID- 28754047
TI  - Introducing Namaste Care to the hospital environment: a pilot study.
AB  - BACKGROUND: The rising prevalence of dementia is impacting on acute hospitals and
      placing increased expectations on health and social care professionals to improve
      the support and services they are delivering. It has been recommended that good
      practice in dementia care relies on adopting a palliative approach to care and
      meeting people's physical, psychological, social and spiritual needs. Increased
      dementia training for staff that includes initiatives that promote dignity;
      enhancing communication skills and recognizing that a person with dementia may be
      approaching the end of their lives are needed. Our study aim was to explore
      whether Namaste Care is an acceptable and effective service for people with
      advanced dementia being cared for on an acute hospital ward. METHODS: This was an
      exploratory qualitative interview, pilot study. Individual, semi-structured, face
      to-face interviews were conducted with hospital healthcare staff working in an
      area of the hospital where Namaste Care had been implemented. Data were analysed
      using the framework approach. RESULTS: Eight interviews were completed with
      members of the multidisciplinary ward team. Two themes were identified: (I)
      difficulties establishing relationships with people with dementia in hospital
      (subthemes: lack of time and resources, lack of confidence leading to fear and
      anxiety); (II) the benefits of a Namaste Care service in an acute hospital
      setting (subthemes: a reduction in agitated behavior; connecting and
      communicating with patients with dementia using the senses; a way of showing
      people with dementia they are cared for and valued). CONCLUSIONS: This small
      scale study indicates that Namaste Case has the potential to improve the quality
      of life of people with advanced dementia being cared for in an acute hospital
      setting. However, further research is required to explore more specifically its
      benefits in terms of improved symptom management and wellbeing of people with
      dementia on acute hospitals wards.

PMID- 28754048
TI  - Barriers to palliative care for advanced dementia: a scoping review.
AB  - People with dementia often fail to receive palliative care, despite increased
      recognition of their need and eligibility for such care. The aims of this study
      were to assess the barriers associated with a lack of implementation of
      palliative care for people with dementia and to explore whether there is a gap in
      knowledge necessitating further study. We reviewed the English literature
      published from 2000 to 2016, related to barriers to palliative care for people
      with dementia. Twenty-two articles met inclusion criteria for the review. Most
      originated in Europe or North America and were qualitative in nature. Four key
      themes were identified: administrative/policy issues, education, communication,
      and staff personal characteristics. Barriers to the delivery of palliative care
      for people with dementia have been studied for more than a decade, yet at
      present, there is a lack of consensus in practice. More research is needed
      related to barriers associated with personal characteristics. Such investigations
      have the potential to improve and better understand the complex nature of
      palliative care in this population.

PMID- 28754049
TI  - The advance care planning experiences of people with dementia, family caregivers
      and professionals: a synthesis of the qualitative literature.
AB  - There exists compelling evidence that advance care planning (ACP) remains a key
      factor in the delivery of appropriate end of life care and facilitates the timely
      transition to palliative care for people with dementia. Take up of ACP within the
      dementia population is low, especially when compared with other conditions.
      Quantitative research has helped in identifying some of the key factors in
      enabling or inhibiting the use of ACP within the dementia population. Qualitative
      research can, however, shed further light upon the experiences of all. We carried
      out a search of the qualitative literature addressing the ACP experiences of
      people with dementia, family caregivers and professionals. An approach to
      qualitative synthesis involving coding of original text, developing descriptive
      themes and generating analytical themes was utilized. We identified five papers
      and subsequently five analytical themes: breadth and scope of future planning;
      challenges to ACP; postponing ACP; confidence in systems and making ACP happen
      for people with dementia. The synthesized findings shed light on the ongoing
      challenges of the use and further development of ACP in the population of people
      with dementia. In particular attention is drawn to the difficulties in the timing
      of ACP and the preference for informal approaches to planning within the families
      of people affected by dementia. The ACP capacity of the workforce is also
      addressed. The paper reveals considerable complexity in undertaking ACP in a
      context of dementia. It is suggested that the preference for informal approaches
      and the timing of initial conversations be considered and that the skills of
      those involved in initiating discussions should be given primacy.

PMID- 28754050
TI  - Palliative care covers more than end-of-life issues: why is this not common
      practice in dementia care and what are the implications?

PMID- 28754051
TI  - Palliative dementia care: lessons from a European perspective.

PMID- 28754052
TI  - Hospices and care homes-similarities and differences in relation to palliative
      care.

PMID- 28754053
TI  - Complex decision making in patients with dementia in an internal medicine
      department.
AB  - With the increase of polymorbidity, extending life expectancy and improving
      treatment options for chronic diseases, the care for dementia is moving into
      other areas of medicine. The length and quality of life with advanced dementia is
      directly dependent on the quality of medical and nursing care, early detection
      and treatment of complications, nutritional support and palliative care plan.
      Significant is also the support for family carers. The key coordinators of care
      for patients with dementia are general practitioners (GPs), geriatricians,
      psychiatrists, and an increasingly important role play internists. Case reports
      of patients admitted to an internal medicine department. Description of clinical
      experiences with caring on patients with dementia. In the internal departments of
      regional hospitals, there is a room for adjustment of the care plan, for
      comprehensive assessment of the patient and for making crucial decisions
      regarding nutrition, treatment of chronic diseases, consideration of previously
      expressed wishes in the context of the patient condition, and potential
      prognostic indicators. This assessment must result in a comprehensive
      documentation and communication with patients, and in the case of advanced
      dementia with their family members. The general internal medicine is very often
      the first place where the patient has a chance to hear about indication for
      palliative care. Without the availability of a multidisciplinary assessment, good
      communication and documentation, it is unrealistic to expect that the hospital
      would provide comprehensive care for patients with dementia.

PMID- 28754054
TI  - Help me, help me.
AB  - Disruptive vocalization and resisting personal care is a problem for staff in
      most skilled nursing facilities. Often these behaviors result in the resident
      being treated with antipsychotics. The Namaste Care program which takes place in
      a calm environment and offers a loving touch approach to care, has been
      successful in eliminating these behaviors. The room or space where Namaste Care
      takes place is as free from disruption as possible and as the resident is
      welcomed into the room, the calming music and scent of lavender surrounds them.
      In this case report, the resident stopped crying out as soon as she entered the
      room. This resident also became comfortable with being touched when touch was
      offered in a slow, loving manner. Much to the delight of staff this had a
      "trickle down" effect as the resident stopped resisting care even when she was
      out of the Namaste Care room. The result was that this resident's last year of
      life was filled with loving care until she took her last breath.

PMID- 28754055
TI  - Wound healing activity of curcumin conjugated to hyaluronic acid: in vitro and in
      vivo evaluation.
AB  - Curcumin is a promising wound healing agent but its clinical application is
      limited due to hydrophobicity and lack of stability. In this article, we report
      the results of a study on wound healing efficacy of curcumin conjugated to
      hyaluronic acid (HA) which is a natural polysaccharide known to influence the
      healing process. Studies on proliferation, antioxidant activity and scratch wound
      healing carried out in human keratinocyte cells revealed that HA-conjugated
      curcumin treatment enhanced cell proliferation, decreased oxidative damage
      induced by H2O2 and also improved migration of cells in scratch wounds as
      compared to treatment with native curcumin. HA conjugated curcumin exhibited
      bactericidal activity in dark and phototoxicity when irradiated with blue light
      against antibiotic resistant bacteria. Furthermore, wound healing efficacy
      studied in diabetic mice demonstrated that topical application of the conjugate
      on wounds led to better healing as compared to treatment with HA-free curcumin
      and HA alone. These results suggest that HA conjugation is a promising
      formulation of curcumin for enhancing its healing efficacy.

PMID- 28754056
TI  - Is atypical depression simply a typical depression with unusual symptoms?

PMID- 28754057
TI  - Risk Assessments of Epidural Analgesia During Labor and Delivery.
AB  - Epidural analgesia (EA) is one of the methods of choice for labor pain relief,
      but its adverse effects on the mother and child remain controversial. The
      objective of this study was to determine whether there is an association between
      the use of EA and different aspects of labor. The author(s) analyzed the effect
      of EA on different aspects of labor in a retrospective cohort observational study
      of deliveries in a public Spanish hospital during a 3-year period. Women with EA
      administration were found to increase the risk of stimulated labor, reduce the
      percentage of spontaneous deliveries, increase the risk of instrumental labor due
      to stalled labor or loss of fetal well-being, and increase the percentage of
      episiotomies. However, women with EA were not and increased risk for perineal
      laceration or the condition of the membranes at the delivery or with the type of
      placental expulsion. Thus, the administration of EA should be assessed in each
      case by the health care professional.

PMID- 28754058
TI  - The impact of socially-accountable, community-engaged medical education on
      graduates in the Central Philippines: Implications for the global rural medical
      workforce.
AB  - INTRODUCTION: Developing and retaining a high quality medical workforce,
      especially within low-resource countries has been a world-wide challenge
      exacerbated by a lack of medical schools, the maldistribution of doctors towards
      urban practice, health system inequities, and training doctors in tertiary
      centers rather than in rural communities. AIM: To describe the impact of socially
      accountable health professional education on graduates; specifically: their
      motivation towards community-based service, preparation for addressing local
      priority health issues, career choices, and practice location. METHODS: Cross
      sectional survey of graduates from two medical schools in the Philippines: the
      University of Manila-School of Health Sciences (SHS-Palo) and a medical school
      with a more conventional curriculum. RESULTS: SHS-Palo graduates had
      significantly (p < 0.05) more positive attitudes to community service. SHS-Palo
      graduates were also more likely to work in rural and remote areas (p < 0.001)
      either at district or provincial hospitals (p = 0.032) or in rural government
      health services (p < 0.001) as Municipal or Public Health Officers (p < 0.001).
      Graduates also stayed longer in both their first medical position (p = 0.028) and
      their current position (p < 0.001). CONCLUSIONS: SHS-Palo medical graduates
      fulfilled a key aim of their socially-accountable institution to develop a health
      professional workforce willing and able, and have a commitment to work in
      underserved rural communties.

PMID- 28754059
TI  - Disrupting the intramolecular interaction between proto-oncogene c-Src SH3 domain
      and its self-binding peptide PPII with rationally designed peptide ligands.
AB  - Proto-oncogene non-receptor tyrosine protein kinase c-Src has been involved in
      the development, progression and metastasis of a variety of human cancers. This
      protein contains two self-binding peptide (SBP) sites separately between the SH3
      domain and polyproline-II (PPII) helix and between the SH2 domain and C-terminal
      phosphorylatable tail (CTPT), which are potential targets of anticancer drugs to
      regulate the kinase activity. Here, we described an integrated protocol to
      systematically investigate the structural basis, energetic property and dynamics
      behaviour of PPII binding to SH3, and to rationally design potent peptide ligands
      to target the SBP site of SH3-PPII interaction. Our study found that the PPII
      peptide is a non-typical binder that can only interact effectively with its
      cognate SH3 domain when it is integrated into the full-length c-Src kinase
      protein; stripping the peptide from the protein would considerably impair SH3
      affinity by increasing entropy penalty upon the domain-peptide binding,
      suggesting that the protein context plays an essential role in the SBP's
      biological function. Next, we identified that the PPII peptide binds to SH3
      domain in a class II manner and, on this basis, we derived a series of modified
      versions of the wild-type PPII peptide using a structure-based rational strategy.
      These modified peptide mutants have been structurally optimized with respect to
      their molecular flexibility and interaction potency with SH3 domain, in order to
      minimize indirect entropy penalty and to maximize direct binding enthalpy
      simultaneously. Consequently, several rationally designed peptides were obtained,
      including PPIIm2 (TSKPQTPGRA), PPIIm5 (KPPTPPRA), PPIIm6 (FPPPPPRA) and PPIIm7
      (YPPLPPRA), which exhibit a moderately or considerably increased affinity (Kd =
      72, 34, 15 and 5.7 MUM, respectively) relative to the wild-type PPII (TSKPQTQGLA)
      (Kd = 160 MUM). These peptides can be used as lead molecular entities to further
      develop new anticancer therapeutics to regulate c-Src kinase activity by
      targeting the SBP site of SH3-PPII interaction.

PMID- 28754060
TI  - The benefits of students as partners for developing digital literacy in medical
      education.

PMID- 28754061
TI  - Is caries equally distributed in adults? A population-based cross-sectional study
      in Norway - the TOHNN-study.
AB  - OBJECTIVES: The aim of the study was to examine the prevalence and distribution
      of dental caries in an adult population and identify factors associated with
      being caries free. MATERIAL AND METHODS: Data were collected from a randomized
      population sample in Northern Norway (N = 1932; 988 women; mean age 47.0 years,
      SD 15.3). The study included a structured questionnaire and a clinical
      examination. The sum of enamel and dentine caries, DS1-5, formed the main outcome
      measures for caries prevalence. RESULTS: Mean DMFT was 15.1 (95% CI 14.8, 15.4),
      mean DFT was 12.0 (CI 11.7, 12.2), and mean DT was 1.1 (CI 1.0, 1.2). The mean
      value for dentine caries (DS3-5) was 0.8 (CI 0.7, 0.9), and mean DS1-5 was 3.8
      (CI 3.6, 4.1). Mean DS1-5 was highest in the youngest age group (mean 6.9, 95% CI
      6.3, 7.6) and in rural areas (mean 5.0, CI 4.4, 5.6). The most caries-prone 20%
      in the youngest age group had 52% of the total number of carious lesions compared
      with 80% in the two oldest age groups. Tooth brushing twice daily (p = .005),
      drinking sugar containing soft drink (p =.029), and attending dental services
      every year (p < .001), were associated with being caries free. CONCLUSION: Dental
      caries is still a common condition, particularly in the youngest age group.
      Living in a rural area, low socioeconomic status, less frequent tooth cleaning
      and sugar containing soft drinks were associated with a higher prevalence of
      dental caries. The different caries distribution among adults calls for different
      preventive strategies at both population and individual levels.

PMID- 28754062
TI  - Procedures and Protocols for Weight Assessment During Acute Illness in
      Individuals With Anorexia Nervosa: A National Survey.
AB  - BACKGROUND: Weight assessment is a key component of nursing care for individuals
      with the acute illness of anorexia nervosa (AN). However, there is little data to
      guide protocols and procedures regarding weight assessment. OBJECTIVE: To
      describe institutional practices regarding weight assessment of individuals
      during acute illness of AN. DESIGN: Treatment facilities ( N = 24) completed a
      survey about written protocols and procedures regarding weight assessment and
      disclosure of weight to patients. RESULTS: The majority of facilities ( n = 22;
      92%) have written protocols for weight assessment. Weight assessments occurred
      mostly in the morning ( n = 23; 95.8%), in hospital gowns ( n = 21; 87.5%), and
      after voiding ( n = 14; 58.3%). Respondents described mixed practices for
      disclosing weight to patients. CONCLUSION: Results indicate widespread
      variability in weight assessment and disclosure of weight. Further research is
      necessary to help develop evidence-based guidelines about weighing practices
      during acute illness for individuals with AN.

PMID- 28754063
TI  - Interjoint coordination of the lower extremities in short-track speed skating.
AB  - In short-track speed skating, the three-dimensional kinematics of the lower
      extremities during the whole skating cycle have not been studied. Kinematic
      parameters of the lower extremities during skating are presented as joint angles
      versus time. However, the angle-time presentation is not sufficient to describe
      the relationship between multi-joint movement patterns. Thus, angle-angle
      presentations were developed and used to describe interjoint coordination in
      sport activities. In this study, 15 professional male skaters' full body motion
      data were recorded using a wearable motion capture system during short-track
      speed skating. We investigated the three-dimensional kinematics of the lower
      extremities and then established the interjoint coordination between hip-knee and
      knee-ankle for both legs during the whole skating cycle. The results demonstrate
      the relationship between multi-joint movements during different phases of short
      track speed skating. This study provides fundamentals of the movement mechanism
      of the lower extremities that can be integrated with physiotherapy to improve
      skating posture and prevent injuries from repetitive stress since physiological
      characteristics play an important role in skating performance.

PMID- 28754064
TI  - Development and characterization dual responsive magnetic nanocomposites for
      targeted drug delivery systems.
AB  - A drug delivery system based on dual responsive units was developed. An appealing
      pH- and thermo-responsive triblock terpolymer as the drug carrier was synthesized
      by RAFT polymerization of N-isopropyl acrylamide and methacrylic acid monomers
      using PEG-RAFT agent. The Fe3O4 magnetic nanoparticles were synthesized by co
      precipitation of Fe salts. Synthesized samples were characterized by FT-IR, XRD,
      GPC, SEM and TEM. The dual responsive behaviour and self-assembly of the triblock
      terpolymers in aqueous solution were investigated using UV-vis transmittance and
      DLS. Based on the results of DLS and TEM, the average size of micelles was 170,
      125 and 30 nm. The triblock terpolymer was used as a chemotherapy drug carrier
      and doxorubicin as a model drug. The release rate of the drug at two different
      temperatures (37  degrees C and 42  degrees C) and pHs (5.8 and 7.4) was studied.
      The in vitro cytotoxicity assay of free doxorubicin and drug-loaded magnetic
      nanoparticles was studied. The MTT assay exhibited that these polymers are
      biocompatible and no toxicity. As well, IC50 of the DOX-loaded triblock
      terpolymer in MTT test demonstrated that these systems could be suitable for the
      treatment of cancer.

PMID- 28754065
TI  - Acute disseminated mycobacteriosis in captive Atlantic guitarfish ( Rhinobatos
      lentiginosus).
AB  - An adult female captive-born Atlantic guitarfish ( Rhinobatos lentiginosus) was
      found acutely moribund on exhibit and died soon after presentation. Abnormalities
      on autopsy were focal cutaneous erythema on the tail, a small liver, many
      variably sized friable ovarian follicles, and coelomic effusion. Histologic
      examination revealed systemic bacterial embolization, and yolk coelomitis with
      minimal associated inflammation and some mineralization. Bacterial culture of
      blood and coelomic effusion grew a rapidly growing Mycobacterium species that was
      further identified as Mycobacterium chelonae by PCR amplification and sequencing
      of the RNA polymerase subunit beta ( rpoB) gene of isolated genomic DNA.
      Concurrent reproductive disease may have caused immunosuppression, thus
      predisposing to the mycobacterial infection. At another institution, an adult
      male wild-caught Atlantic guitarfish was found dead on exhibit with no
      premonitory signs. Abnormalities on autopsy were a thin body condition, small
      liver, and coelomic effusion. Histologic examination revealed acute mycobacterial
      septicemia. M. chelonae was also identified in this fish by PCR amplification and
      sequencing. Mycobacteriosis has rarely been reported in captive elasmobranchs.
      Guitarfish may have greater susceptibility to mycobacteriosis than other
      elasmobranchs, and acute and chronic manifestations of the disease may exist in
      this species.

PMID- 28754066
TI  - Pulse pressure tracking from adolescence to young adulthood: contributions to
      vascular health.
AB  - PURPOSE: We examined whether exposure to high PP in adolescence predicts carotid
      artery intima-media thickness (IMT) and stiffness indices at young adulthood.
      METHODS: Seventy-nine participants had their brachial systolic (SBP) and
      diastolic blood (DBP) pressures taken at the age of 15-16 years and later at
      young adulthood (29-31 years). Carotid IMT, distensibility and stiffness index
      beta were measured at young adulthood. Linear and logistical regression analysis
      were performed. RESULTS: PP at adolescence and at young adulthood predicted
      vascular health independently of sex, body mass index, and mean arterial
      pressure, explaining up to 37% of the variance. When analyzing its single
      constituents, at adolescence DBP was more predictive of vascular health, whereas
      DBP and SBP were equally important at young adulthood. Adolescents with high PP
      were at risk for increased carotid IMT (OR: 4.04-4.09), even if PP decreased at
      young adulthood. Young adults with high PP were at risk for increased stiffness
      regardless of adolescence PP (OR: 4.64-7.35). CONCLUSION: PP at adolescence and
      young adulthood may be a better predictor of early pathological changes in
      carotid artery structure and stiffness. Whereas carotid IMT in young adults
      appears to be influenced by PP at adolescence, carotid stiffness depends
      primarily on current PP.

PMID- 28754067
TI  - Using Virtual Patient Simulations to Prepare Primary Health Care Professionals to
      Conduct Substance Use and Mental Health Screening and Brief Intervention.
AB  - BACKGROUND: Primary health care professionals are in an excellent position to
      identify, screen, and conduct brief interventions for patients with mental health
      and substance use disorders. However, discomfort in initiating conversations
      about behavioral health, time concerns, lack of knowledge about screening tools,
      and treatment resources are barriers. OBJECTIVE: This study examines the impact
      of an online simulation where users practice role-playing with emotionally
      responsive virtual patients to learn motivational interviewing strategies to
      better manage screening, brief interventions, and referral conversations. DESIGN:
      Baseline data were collected from 227 participants who were then randomly
      assigned into the treatment or wait-list control groups. Treatment group
      participants then completed the simulation, postsimulation survey, and 3-month
      follow-up survey. RESULTS: Results showed significant increases in
      knowledge/skill to identify and engage in collaborative decision making with
      patients. CONCLUSIONS: Results strongly suggest that role-play simulation
      experiences can be an effective means of teaching screening and brief
      intervention.

PMID- 28754068
TI  - A new head-mounted display-based augmented reality system in neurosurgical
      oncology: a study on phantom.
AB  - PURPOSE: Benefits of minimally invasive neurosurgery mandate the development of
      ergonomic paradigms for neuronavigation. Augmented Reality (AR) systems can
      overcome the shortcomings of commercial neuronavigators. The aim of this work is
      to apply a novel AR system, based on a head-mounted stereoscopic video see
      through display, as an aid in complex neurological lesion targeting.
      Effectiveness was investigated on a newly designed patient-specific head
      mannequin featuring an anatomically realistic brain phantom with embedded
      synthetically created tumors and eloquent areas. MATERIALS AND METHODS: A two
      phase evaluation process was adopted in a simulated small tumor resection
      adjacent to Broca's area. Phase I involved nine subjects without neurosurgical
      training in performing spatial judgment tasks. In Phase II, three surgeons were
      involved in assessing the effectiveness of the AR-neuronavigator in performing
      brain tumor targeting on a patient-specific head phantom. RESULTS: Phase I
      revealed the ability of the AR scene to evoke depth perception under different
      visualization modalities. Phase II confirmed the potentialities of the AR
      neuronavigator in aiding the determination of the optimal surgical access to the
      surgical target. CONCLUSIONS: The AR-neuronavigator is intuitive, easy-to-use,
      and provides three-dimensional augmented information in a perceptually-correct
      way. The system proved to be effective in guiding skin incision, craniotomy, and
      lesion targeting. The preliminary results encourage a structured study to prove
      clinical effectiveness. Moreover, our testing platform might be used to
      facilitate training in brain tumour resection procedures.

PMID- 28754069
TI  - Axonal spheroids in ovine neuroaxonal dystrophy are immunopositive to kinesin and
      dynein.
AB  - Neuroaxonal dystrophy (NAD) is a neurologic disorder of sheep characterized by
      accumulation of numerous axonal swellings (spheroids) in specific regions of the
      brainstem and spinal cord. Disruption of axonal transport, which is driven in
      anterograde and retrograde directions by the molecular motors, kinesin and
      dynein, respectively, is believed to contribute to spheroid development.
      Accordingly, we examined spheroids in ovine NAD cases immunohistochemically for
      kinesin and dynein and found both motor proteins, with dynein more strongly
      expressed than kinesin. Further investigations of the kinesin and dynein content
      of axonal spheroids in NAD, and other neurodegenerative disorders of domestic
      animals, could assist in better understanding the pathogenesis of these diseases.

PMID- 28754070
TI  - The Milieu Manager: A Nursing Staffing Strategy to Reduce Observer Use in the
      Acute Psychiatric Inpatient Setting.
AB  - BACKGROUND: Rising acuity levels in inpatient settings have led to growing
      reliance on observers and increased the cost of care. OBJECTIVES: Minimizing use
      of observers, maintaining quality and safety of care, and improving bed access,
      without increasing cost. DESIGN: Nursing staff on two inpatient psychiatric units
      at an academic medical center pilot-tested the use of a "milieu manager" to
      address rising patient acuity and growing reliance on observers. Nursing cost,
      occupancy, discharge volume, unit closures, observer expense, and incremental
      nursing costs were tracked. Staff satisfaction and reported patient
      behavioral/safety events were assessed. RESULTS: The pilot initiatives ran for 8
      months. Unit/bed closures fell to zero on both units. Occupancy, patient days,
      and discharges increased. Incremental nursing cost was offset by reduction in
      observer expense and by revenue from increases in occupancy and patient days.
      Staff work satisfaction improved and measures of patient safety were unchanged.
      CONCLUSIONS: The intervention was effective in reducing observation expense and
      improved occupancy and patient days while maintaining patient safety,
      representing a cost-effective and safe approach for management of acuity on
      inpatient psychiatric units.

PMID- 28754071
TI  - A review of pharmacotherapy for treating gastroesophageal reflux disease (GERD).
AB  - INTRODUCTION: Medical therapy of gastroesophageal reflux disease (GERD) is based
      on the use of proton pump inhibitors (PPIs) as first choice treatment. Despite
      their effectiveness, about 20-30% of patients report an inadequate response and
      alternative drugs are required. Areas covered: This review provides an overview
      of current pharmacotherapy for treating GERD by showing the results of PPIs,
      reflux inhibitors, antidepressants and mucosa protective medications. Expert
      opinion: Medical therapy of GERD does not definitely cure the disease, because
      even PPIs are not able to change the key factors responsible for it. However,
      they remain the mainstay of medical treatment, allowing us to alleviate symptoms,
      heal esophagitis and prevent complications in the majority of cases.
      Nevertheless, many patients do not respond, because acid does not play any
      pathogenetic role. Prokinetics and reflux inhibitors have the potential to
      control motor abnormalities, but the results of clinical trials are inconsistent.
      Antidepressant drugs are effective in specific subgroups of NERD patients with
      visceral hypersensitivity, but larger, controlled clinical studies are necessary.
      Protective drugs or medical devices have been recently adopted to reinforce
      mucosal resistance and preliminary trials have confirmed their efficacy either
      combined with or as add-on medication to PPIs in refractory patients.

PMID- 28754072
TI  - Blockade of the angiotensin system improves mental health domain of quality of
      life: A meta-analysis of randomized clinical trials.
AB  - OBJECTIVE: It is unclear whether blockade of the angiotensin system has effects
      on mental health. Our objective was to determine the impact of angiotensin
      converting enzyme inhibitors and angiotensin II type 1 receptor (AT1R) blockers
      on mental health domain of quality of life. STUDY DESIGN: Meta-analysis of
      published literature. DATA SOURCES: PubMed and clinicaltrials.gov databases. The
      last search was conducted in January 2017. STUDY SELECTION: Randomized controlled
      trials comparing any angiotensin converting enzyme inhibitor or AT1R blocker
      versus placebo or non-angiotensin converting enzyme inhibitor or non-AT1R blocker
      were selected. Study participants were adults without any major physical
      symptoms. We adhered to meta-analysis reporting methods as per PRISMA and the
      Cochrane Collaboration. DATA SYNTHESIS: Eleven studies were included in the
      analysis. When compared with placebo or other antihypertensive medications, AT1R
      blockers and angiotensin converting enzyme inhibitors were associated with
      improved overall quality of life (standard mean difference = 0.11, 95% confidence
      interval = [0.08, 0.14], p < 0.0001), positive wellbeing (standard mean
      difference = 0.11, 95% confidence interval = [0.05, 0.17], p < 0.0001), mental
      (standard mean difference = 0.15, 95% confidence interval = [0.06, 0.25], p <
      0.0001), and anxiety (standard mean difference = 0.08, 95% confidence interval =
      [0.01, 0.16], p < 0.0001) domains of QoL. No significant difference was found for
      the depression domain (standard mean difference = 0.05, 95% confidence interval =
      [0.02, 0.12], p = 0.15). CONCLUSIONS: Use of angiotensin blockers and inhibitors
      for the treatment of hypertension in otherwise healthy adults is associated with
      improved mental health domains of quality of life. Mental health quality of life
      was a secondary outcome in the included studies. Research specifically designed
      to analyse the usefulness of drugs that block the angiotensin system is necessary
      to properly evaluate this novel psychiatric target.

PMID- 28754073
TI  - TP53 gene expression levels and tumor aggressiveness in canine mammary
      carcinomas.
AB  - The protein p53 is considered to be one of the most important tumor suppressor
      factors. Despite this importance, a potential association between TP53 messenger
      (m)RNA levels and tumor aggressiveness has not been well defined in animal
      cancer. We assessed and correlated TP53 gene expression in 40 canine mammary
      carcinomas with histologic grade, tumor size, and aggressiveness. The tumors were
      subjected to histologic analysis and the TP53 mRNA levels determined by RT-rtPCR.
      Statistical analysis revealed no correlation between levels of TP53 mRNA and
      tumor aggressiveness ( r = 0.00) or tumor growth ( r = 0.06). Histologic grades (
      r = 0.17) and mitosis count ( r = 0.12) showed a weak correlation with TP53 mRNA
      expression levels. These findings are consistent with molecular studies that
      revealed heterogeneous expression of TP53 in canine and human mammary tumors.
      Hence, TP53 gene expression alone cannot be considered a marker for tumor
      aggressiveness in canine mammary carcinomas.

PMID- 28754074
TI  - Detection of Mycoplasma spp., herpesviruses, topiviruses, and ferlaviruses in
      samples from chelonians in Europe.
AB  - We tested samples from 1,015 chelonians in Europe for Mycoplasma spp.,
      herpesviruses, ranaviruses, picornaviruses, and ferlaviruses by PCR. Mycoplasma
      spp. were detected in 42.1% and herpesviruses were detected in 8.0% of tested
      chelonians. Differentiation of the herpesviruses revealed that 46.9% of the
      detected chelonian viruses were testudinid herpesvirus 1 (TeHV-1) and 54.3% were
      TeHV-3, including co-detections of TeHV-1 and -3 in 3 tortoises. TeHV-4 was
      detected in a leopard tortoise ( Stigmochelys pardalis), and a herpesvirus that
      could not be further characterized was found in a pond slider ( Trachemys
      scripta). Picornaviruses (topiviruses) were detected in 2.2% of the tested
      animals; ferlaviruses were found in 0.6%; no ranaviruses were detected in any of
      the animals tested. Mycoplasma spp. were detected significantly more often in
      Horsfield's tortoises ( Testudo horsfieldii), leopard tortoises, and Indian star
      tortoises ( Geochelone elegans) than in other species. Horsfield's tortoises were
      also significantly more often positive for TeHV-1. Mycoplasma and TeHV-1 were co
      detected in 3.0%, and mycoplasma and TeHV-3 in 2.3%. The TeHV-4-positive tortoise
      was also positive for mycoplasma. Mycoplasma and picornaviruses were co-detected
      in 1.2% of the tortoises. A spur-thighed tortoise ( Testudo graeca) was positive
      for mycoplasma and a ferlavirus. In some cases, >2 pathogens were detected. A
      significant correlation between mycoplasma and herpesvirus detection was found.
      Of all tested animals, 47.6% were positive for at least one pathogen,
      demonstrating the importance of pathogen detection in captive chelonians.

PMID- 28754075
TI  - Oval housing for the St. Jude Medical bileaflet mechanical heart valve.
AB  - The St. Jude Medical bileaflet mechanical heart valve was approved by the Food
      and Drug Administration in late 1970s. The basic idea for the design of the valve
      is simply two semicircular flat plates pivoting on hinges. The overall
      performance of St. Jude Medical valves such as blood flow being central, the
      leaflets opening completely, and the pressure drop across the valve being trivial
      is satisfactory. St. Jude Medical valves provide an improved hemodynamics
      compared to the other mechanical heart valve models; however, their non
      physiological hemodynamics which may lead to red blood cells lysis and
      thrombogenicity still remains a major issue. In this study, we hypothesize that
      applying ovality to the housing might improve their hemodynamics significantly
      which is based on the fact that the native annulus is oval by nature. A quick but
      precise numerical model based on the finite strip method was developed by which
      the regurgitation flow volume and velocity of the proposed design were assessed
      in the closing phase. The results are satisfactory and an improved hemodynamics
      is observed. The proposed design can be considered for further numerical and
      experimental studies and shows promise and merits further development.

PMID- 28754076
TI  - Immunologic detection of Giardia duodenalis in a specific pathogen-free captive
      olive baboon ( Papio cynocephalus anubis) colony.
AB  - Several commercial Giardia immunoassays were evaluated in baboons for sensitivity
      and specificity as well as ease of use in a large specific pathogen-free (SPF)
      colony. An additional objective was to identify the assemblage(s) of Giardia
      duodenalis present in this baboon colony. A direct immunofluorescent antibody
      test (IFAT) was used as the reference test. Tests evaluated were a patient-side
      rapid test for dogs and cats, a human rapid test, and a well-plate ELISA designed
      for use with humans. Test sensitivities and specificities were compared using the
      McNemar paired t-test and were further evaluated for agreement using an
      unweighted Cohen kappa statistic. When compared to the IFAT reference, both human
      tests were more sensitive than the veterinary test. Based on PCR and sequencing
      of the G. duodenalis small-subunit ribosomal RNA and glutamate dehydrogenase
      loci, assemblage AI was present in this baboon colony. We found that 10 of the
      110 (9%) baboons in this SPF colony were infected with a zoonotic strain of G.
      duodenalis.

PMID- 28754077
TI  - Treatment of the donor site of free radial flaps: vacuum sealing versus
      conventional wound care.
AB  - INTRODUCTION: Radial forearm flap donor side defects can be treated by vacuum
      therapy and conventional wound dressing. The aim of this study was to compare
      different wound management considering wound healing, including risk factors and
      cost effectiveness. MATERIALS AND METHODS: Retrospective study including patients
      treated with radial flaps in the Department of Head and Neck Surgery in Erlangen
      from January 2005 to August 2013. Wound healing was assessed regarding
      complications considering several risk factors and comorbidities. Data were
      analyzed comparing conventional dressing and vacuum therapy, including a
      calculation of costs. RESULTS: The study included 138 patients (n = 55
      conventional dressing; n = 83 vacuum dressing). The incidence of wound
      complications in the vacuum group was 50.6 and 32.7% in the conventional dressing
      group (p = .058). The presence of risk factors and comorbidities did not have
      significant impact on the occurrence of complications. Costs for vacuum therapy
      turned out to be at least five times higher. CONCLUSION: In view of the current
      state of research, these results show that using vacuum dressings has no
      significant benefit in the wound management of forearm donor side defect covered
      with full-thickness skin grafts. If the costs and economical aspects are also
      considered, conventional wound dressing may be preferred.

PMID- 28754078
TI  - 3D simulation assisted resection of giant hepatic mesenchymal hamartoma in
      children.
AB  - OBJECTIVE: To evaluate the usefulness of Hisense Computer Assisted Surgery System
      (Hisense CAS) in pre-operative surgical planning and intra-operative navigation
      for resection of pediatric giant hepatic mesenchymal hamartoma (HMH). METHODS:
      Five children with HMH underwent hepatectomy in our hospital. Pre-operative
      abdominal enhanced CT was performed for diagnosis and treatment planning. Using
      CT DICOM files, three-dimensional reconstruction was performed in three cases for
      operation planning and intra-operative navigation, with SID carrying out precise
      liver resection during the operation with Hisense CAS. RESULT: Two patients
      underwent right and left lobe hepatectomy, respectively, based only on enhanced
      CT. In 3 patients, by using the Hisense CAS system, three-dimensional
      reconstruction of the liver and tumors was successfully completed, and virtual
      hepatectomy performed successfully according to surgical plans. Hisense CAS could
      clearly and directly indicate the HMH location and shape, as well as its
      relationship with the intra-hepatic Glisson system, assisting safe hepatectomy.
      All five patients recovered well from surgery without any complications, and
      pathological examinations confirmed that all cases were HMH. No recurrence was
      observed during the follow-up period of 3 months to 5 years. CONCLUSION: Hisense
      CAS system is useful for preoperative planning and intra-operative navigation,
      assisting safer hepatectomy.

PMID- 28754079
TI  - Plunging ranula - patient characteristics, treatment, and comparison between
      different populations.
AB  - OBJECTIVES: To review our clinical experience and characteristics of Finnish
      patients with plunging ranula and compare our results with reports from other
      populations. DESIGN: A retrospective study from the electronic hospital records
      between 2005 and 2016. SETTING: The Department of Otorhinolaryngology and Head
      and Neck Surgery of Helsinki University Hospital, Finland. RESULTS: We describe
      the characteristics and treatment of 41 patients with MRI-confirmed plunging
      ranula. Most of our patients were young adults and 88% of them were male. Surgery
      and sclerotherapy were used for treatment. CONCLUSIONS: The vast majority of
      Finnish plunging ranula patients in our cohort were male, suggesting significant
      population-related differences in plunging ranula gender distribution. Transoral
      surgery seemed to result in lowest recurrence rate and was the most common
      treatment in our clinic.

PMID- 28754080
TI  - Diagnostic accuracy of phosphor plate systems and conventional radiography in the
      detection of simulated internal root resorption.
AB  - OBJECTIVE: To evaluate the performance of conventional radiography and
      photostimulable phosphor (PSP) plate in the detection of simulated internal root
      resorption (IRR) lesions in early stages. MATERIALS AND METHODS: Twenty single
      rooted teeth were X-rayed before and after having a simulated IRR early lesion.
      Three imaging systems were used: Kodak InSight dental film and two PSPs digital
      systems, Digora Optime and VistaScan. The digital images were displayed on a
      20.1" LCD monitor using the native software of each system, and the conventional
      radiographs were evaluated on a masked light box. Two radiologists were asked to
      indicate the presence or absence of IRR and, after two weeks, all images were re
      evaluated. Cohen's kappa coefficient was calculated to assess intra- and
      interobserver agreement. The three imaging systems were compared using the
      Kruskal-Wallis test. RESULTS: For interexaminer agreement, overall kappa values
      were 0.70, 0.65 and 0.70 for conventional film, Digora Optima and VistaScan,
      respectively. Both the conventional and digital radiography presented low
      sensitivity, specificity, accuracy, positive and negative predictive values with
      no significant difference between imaging systems (p = .0725). CONCLUSIONS: The
      performance of conventional and PSP was similar in the detection of simulated IRR
      lesions in early stages with low accuracy.

PMID- 28754081
TI  - Pulmonary capillary hemangiomatosis and hypertrophic cardiomyopathy in a Persian
      cat.
AB  - Pulmonary capillary hemangiomatosis (PCH) and pulmonary veno-occlusive disease
      (PVOD) are rare causes of primary pulmonary hypertension in humans, and, in 2016,
      were reported in dogs. A 1-y-old, neutered male Persian cat was presented for
      autopsy after sudden death several hours after grooming. Grossly, the lungs were
      mottled red-to-pink, contained rubbery-to-firm nodular foci, and there was
      moderate-to-marked left-sided cardiomegaly and left atrial dilation, consistent
      with hypertrophic cardiomyopathy. Microscopically, there was multifocal to
      regionally extensive capillary proliferation within pulmonary alveolar septa and
      around respiratory bronchioles, with nodular aggregates of densely arranged
      capillaries that replaced pulmonary alveolar spaces. Rare occlusive venous
      remodeling was identified in Verhoeff-van Gieson-stained sections. The gross and
      microscopic changes were consistent with PCH with rare features of PVOD.
      Hypertrophic cardiomyopathy was interpreted as potentially contributing to the
      cause of death, but unrelated to the pulmonary vascular proliferation.

PMID- 28754082
TI  - Serum amyloid A in the diagnosis of feline sepsis.
AB  - Systemic inflammatory response syndrome (SIRS) and sepsis can be challenging to
      diagnose in cats. Retrospectively, we investigated the diagnostic and prognostic
      potential of serum amyloid A (SAA), a major feline acute-phase protein (APP), in
      a population of critically ill cats with SIRS related to trauma or sepsis. A
      total of 56 SIRS cats (trauma n = 27; sepsis n = 29) were included and compared
      with healthy controls ( n = 18). SAA concentration was significantly increased in
      SIRS cats compared to controls, confirming its potential for the detection of
      systemic inflammation in this species. Significantly higher values of SAA were
      detected in cats belonging to the sepsis group; however, according to the results
      of the receiver operating characteristic curve analysis, the value of using SAA
      (>81 mg/L) to discriminate septic cats was only moderate (AUC = 0.76).
      Additionally, cats with sepsis had significantly higher serum bilirubin
      concentrations and toxic neutrophil changes compared to the trauma group.
      Overall, 38 of 56 cats were survivors; 18 of 56 were non-survivors, with 83% of
      the non-survivors (15 of 18) belonging to the sepsis group. Serum bilirubin
      concentration, but not SAA, was able to predict outcome. Prospective studies are
      needed to assess the potential of SAA in the diagnosis of feline sepsis and
      outcome prediction.

PMID- 28754083
TI  - Associations between ectodermal dysplasia, psychological distress and quality of
      life in a group of adults with oligodontia.
AB  - OBJECTIVE: The aim of this study was to assess demographics, self-reported signs
      of ectodermal dysplasia (problems with hair, nails, skin and sweat glands),
      present teeth, previous dental treatment, psychological distress and QoL in
      individuals with oligodontia, and to explore the associations between these
      factors. We also aimed to compare the level of psychological distress and QoL
      between the study group and normative samples. METHODS: Forty-seven individuals
      with oligodontia registered at a resource centre in Norway were included in the
      study. The participants completed self-administered questionnaires on
      demographics, ED signs, dental treatments, psychological distress and QoL
      (overall, health-related- and oral health-related QoL). Relevant statistics
      (independent t-test, correlation analysis and hierarchical multiple regressions)
      were used. RESULTS: Thirty-five participants reported ED signs. Forty-one
      participants had tooth replacements (nine had removable dentures). Sixteen had
      <=10 present teeth, 13 perceived dry mouth and seven were unemployed. Persons
      with <=10 present teeth had higher anxiety- and depression-scores than those
      having >10 present teeth. Unemployment, dry mouth and removable dentures
      indicated poor health-related- and oral health related QoL. Compared to a
      normative sample; the study group had significantly poorer mental health (MH)
      related QoL, mean (SD); (51.1(8.2) versus 46.8(9.3), p < .001) and more anxiety,
      mean (SD); (4.5(3.1) versus 6.7(3.6), p < .001). ED signs and treatments were
      most important for psychological distress and MH related QoL (MCS), whereas
      demographic parameters were most important for the other QoL measures.
      CONCLUSIONS: The psychological burden of oligodontia is significant, emphasizing
      the importance of a holistic approach by caregivers.

PMID- 28754084
TI  - Response to Driscoll.

PMID- 28754085
TI  - Regarding "A Comparison of Fish Oil Sources for Parenteral Lipid Emulsions in a
      Murine Model".

PMID- 28754086
TI  - JPEN Journal Club 28. Dealing With Dropouts.

PMID- 28754087
TI  - Taurolidine susceptibility of methicillin-resistant Staphylococcus
      pseudintermedius isolates.
AB  - Infections caused by methicillin-resistant Staphylococcus pseudintermedius (MRSP)
      can be challenging to treat because they are often resistant to many other
      antimicrobial agents. We assessed the susceptibility of 29 MRSP isolates from
      dogs to taurolidine in vitro. There was no growth at 0.12% taurolidine and light
      growth at 0.06% for all isolates. Taurolidine was reliable at inhibiting growth
      of MRSP at a concentration of 1,200 ug/mL.

PMID- 28754088
TI  - A novel targeted angiogenesis technique using VEGF conjugated magnetic
      nanoparticles and in-vitro endothelial barrier crossing.
AB  - BACKGROUND: Vascular endothelial growth factor is well known for its angiogenesis
      potential. The study was performed to determine the possible pro-angiogenic role
      of magnetic nanoparticles coupled to VEGF in vitro and their capacity to cross an
      endothelial monolayer. This novel treatment technique for angiogenesis could be
      potentially useful for therapeutic purposes using magnetic nanoparticles.
      METHODS: Magnetic nanoparticles (MN) were synthesized and were conjugated with
      the vascular endothelial growth factor. The particles were tested in vitro in a
      2D to 3D culture system. MN was seeded in different positions in relation to an
      HUVEC spheroid to assess a preferential migration. To evaluate the MN capacity to
      cross the endothelial barrier, a confluent monolayer of HUVEC cells was seeded on
      top of a collagen gel. MN was placed in dissolution on the cell culture media,
      and the MN position was determined by confocal microscopy for 24 h. RESULTS:
      HUVEC spheroids were able to generate a preferential sprouting depending on the
      MN position. Meanwhile, there was random migration when the MN's were placed all
      over the collagen gel and no sprouting when no MN was added. The trans
      endothelial migration capacity of the MN was observed after 20 h in culture in
      the absence of external stimuli. CONCLUSION: Here we show in vitro angiogenesis
      following the distribution of the MN conjugated with growth factors. These
      nanoparticles could be controlled with a magnet to place them in the ischemic
      area of interest and speed up vascular recovery. Also, MN has potentials to cross
      endothelium, opening the doors to a possible intravascular and extravascular
      treatment.

PMID- 28754089
TI  - Predictive factors and prevalence of microalbuminuria in HIV-infected patients: a
      cross-sectional analysis.
AB  - BACKGROUND: Renal dysfunction is a common problem in the HIV+ population, due to
      the effect of both the HIV virus and the several classes of ARV drugs such as
      tenofovir (TDF). It is also known that the presence of renal damage correlates
      with cardiovascular risk and therefore with the risk of mortality of the patients
      accordingly. The detection of early renal damage is very important. Albuminuria
      and microalbuminuria are markers of early kidney disease and cardiovascular risk.
      The aim of the study is to evaluate the prevalence of microalbuminuria in a large
      polycentric sample, of unselected and consecutive HIV-patients followed as
      outpatients, and to assess its association with different therapeutic regimens.
      METHODS: We studied 326 patients with a mean age of 48.4 +/- 1.6 years, treated
      at the Infectious Diseases Clinics of Chieti and Perugia for 48 weeks. The main
      metabolic parameters and the microalbuminuria levels in a single sample of urine
      were evaluated. RESULTS: Microalbuminuria was detected in 61.0% of patients at T0
      and in 49.7% after 48 weeks of observation with a median values of 1.1 mg/L (IQR:
      0-2.7) vs. 0 mg/L (IQR: 0-2.0). 70% of the enrolled population did not show
      changes in microalbuminuria levels over time, 19% showed improvement, and 11% of
      the population had a worsening of microalbuminuria levels without any alteration
      of creatinine, uric acid and GFR-MDRD. We also found a statistically significant
      association between the development of microalbuminuria and gender (p < 0.035),
      Arterial Hypertension (AH) (p < 0.028) and therapy with TDF (p < 0.050).
      CONCLUSION: We showed a very high prevalence of microalbuminuria, much higher
      than the literature data; the use of TDF affects the renal function in a
      statistically significant way and should therefore be considered a risk factor
      for kidney damage, which can be early assessed with the measurement of
      microalbuminuria.

PMID- 28754090
TI  - Association of serum C1q/TNF-related protein-3 (CTRP-3) in patients with coronary
      artery disease.
AB  - BACKGROUND: Recent studies have demonstrated that complement C1q tumor necrosis
      factor related proteins (CTRPs) have diverse biological influences on the
      cardiovascular system. CTRP 3 is a member of the CTRP superfamily, which may play
      a pivotal role in the pathogenesis of coronary artery disease (CAD). Here, we
      investigated whether serum levels of CTRP 3 are associated with the prevalence
      and the severity of CAD. METHODS: In this study, 145 eligible participants were
      included who underwent coronary angiography. According to the result of the
      coronary angiography, all participants were divided into two groups: non-CAD
      group (n = 66) and CAD group (n = 79). The CAD group was further divided into
      single-vessel (n = 25), double-vessel (n = 30) and triple-vessel (n = 24) disease
      groups in line with different lesioned vessels of CAD. Plasma CTRP 3
      concentration was determined by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: Serum levels of CTRP 3 were significantly higher in CAD patients than in
      non-CAD patients (CAD: 56.68 +/- 3.63 ng/ml, non-CAD: 44.10 +/- 3.20 ng/ml, p <
      0.01). Significant differences of CTRP 3 levels were also found between single
      vessel group and triple-vessel group (single-vessel group: 44.80 +/- 3.14 ng/ml,
      triple-vessel group: 75.07 +/- 9.41 ng/ml, p < 0.005). Multiple logistic
      regression analysis revealed that CTRP 3 levels, together with HDL cholesterol
      and glucose, correlated with CAD. CONCLUSIONS: Elevated serum CTRP 3 levels were
      closely related to the prevalence and severity of CAD, suggesting that it might
      be regarded as a novel biomarker for CAD.

PMID- 28754091
TI  - "Visually impaired elderly patient ingests pill desiccant, leading to acute
      hypoxic respiratory failure requiring intubation".
AB  - BACKGROUND: A significant percentage of elderly patients suffer from both
      polypharmacy and visual impairment. This combination can increase the risk of an
      adverse event related to medication. This case highlights an unusual, but
      potentially deadly, medication adverse event. CASE PRESENTATION: A 77-year-old
      male, visually impaired, ingested a pill desiccant, believing it was the
      ampicillin/sulbactam tablet he was prescribed for an infected diabetic foot
      ulcer. He presented to the emergency room with inability to swallow, and imaging
      revealed the pill desiccant lodged in his upper esophagus. He developed
      respiratory distress due to aspiration of secretions, necessitating intubation
      both to protect his airway and for an esophagogastroduodenoscopy (EGD). During
      EGD the desiccant was pushed into the stomach due to an inability to remove it
      without causing harm. Patient self-extubated the following day and per family and
      patient's wishes was not re-intubated. The patient suffered no further
      complications directly related to the desiccant, but he died several days later
      from respiratory failure. CONCLUSIONS: This case highlights a concerning
      medication patient safety issue for visually impaired geriatric patients.

PMID- 28754092
TI  - Peripheral blood lymphocytes immunophenotyping predicts disease activity in
      clinically isolated syndrome patients.
AB  - BACKGROUND: Clinically isolated syndrome (CIS) represents first neurological
      symptoms suggestive of demyelinating lesion in the central nervous system (CNS).
      Currently, there are no sufficient immunological or genetic markers predicting
      relapse and disability progression, nor there is evidence of the efficacy of
      registered disease modifying treatments (DMTs), such as intramuscular interferon
      beta1a. The aim of the study is to evaluate immunological predictors of a relapse
      or disability progression. METHODS: One hundred and eighty one patients with CIS
      were treated with interferon beta1a and followed over the period of 4 years.
      Lymphocyte subsets were analyzed by flow cytometry. A Kaplan-Meier estimator of
      survival probability was used to analyze prognosis. For statistical assessment
      only individual differences between baseline values and values at the time of
      relapse or confirmed disability progression were analysed. RESULTS: Higher levels
      of B lymphocytes predicted relapse-free status. On the other hand, a decrease of
      the naive subset of cells (CD45RA+ in CD4+) after 12, 24, and 36 months of follow
      up were associated with an increased risk of confirmed disability progression.
      CONCLUSION: Our data suggest that the quantification of lymphocyte subsets in
      patients after the first demyelinating event suggestive of MS may be an important
      biomarker.

PMID- 28754093
TI  - A comparison of the conditional inference survival forest model to random
      survival forests based on a simulation study as well as on two applications with
      time-to-event data.
AB  - BACKGROUND: Random survival forest (RSF) models have been identified as
      alternative methods to the Cox proportional hazards model in analysing time-to
      event data. These methods, however, have been criticised for the bias that
      results from favouring covariates with many split-points and hence conditional
      inference forests for time-to-event data have been suggested. Conditional
      inference forests (CIF) are known to correct the bias in RSF models by separating
      the procedure for the best covariate to split on from that of the best split
      point search for the selected covariate. METHODS: In this study, we compare the
      random survival forest model to the conditional inference model (CIF) using
      twenty-two simulated time-to-event datasets. We also analysed two real time-to
      event datasets. The first dataset is based on the survival of children under-five
      years of age in Uganda and it consists of categorical covariates with most of
      them having more than two levels (many split-points). The second dataset is based
      on the survival of patients with extremely drug resistant tuberculosis (XDR TB)
      which consists of mainly categorical covariates with two levels (few split
      points). RESULTS: The study findings indicate that the conditional inference
      forest model is superior to random survival forest models in analysing time-to
      event data that consists of covariates with many split-points based on the values
      of the bootstrap cross-validated estimates for integrated Brier scores. However,
      conditional inference forests perform comparably similar to random survival
      forests models in analysing time-to-event data consisting of covariates with
      fewer split-points. CONCLUSION: Although survival forests are promising methods
      in analysing time-to-event data, it is important to identify the best forest
      model for analysis based on the nature of covariates of the dataset in question.

PMID- 28754094
TI  - The global prevalence of postpartum psychosis: a systematic review.
AB  - BACKGROUND: Mental health is a significant contributor to global burden of
      disease and the consequences of perinatal psychiatric morbidity can be
      substantial. We aimed to obtain global estimates of puerperal psychosis
      prevalence based on population-based samples and to understand how postpartum
      psychosis is assessed and captured among included studies. METHODS: In June 2014,
      we searched PubMed, CiNAHL, EMBASE, PsycINFO, Sociological Collections, and
      Global Index Medicus for publications since the year 1990. Criteria for inclusion
      in the systematic review were: use of primary data relevant to pre-defined mental
      health conditions, specified dates of data collection, limited to data from 1990
      onwards, sample size >200 and a clear description of methodology. Data were
      extracted from published peer reviewed articles. RESULTS: The search yielded
      24,273 publications, of which six studies met the criteria. Five studies reported
      incidence of puerperal psychosis (ranging from 0.89 to 2.6 in 1000 women) and one
      reported prevalence of psychosis (5 in 1000). Due to the heterogeneity of
      methodologies used across studies in definitions and assessments used to identify
      cases, data was not pooled to calculate a global estimate of risk. CONCLUSIONS:
      This review confirms the relatively low rate of puerperal psychosis; yet given
      the potential for serious consequences, this morbidity is significant from a
      global public health perspective. Further attention to consistent detection of
      puerperal psychosis can help provide appropriate treatment to prevent harmful
      consequences for both mother and baby.

PMID- 28754095
TI  - Comparison of neuropsychiatric symptoms and diffusion tensor imaging correlates
      among patients with subcortical ischemic vascular disease and Alzheimer's
      disease.
AB  - BACKGROUND: The causes of behavioral and psychological symptoms of dementia
      (BPSD) vary according to the dementia subtype and associated neuropathology. The
      present study aimed to (i) compare BPSD between patients with subcortical
      ischemic vascular disease (SIVD) and Alzheimer's disease (AD) across stages, and
      (ii) explore the associations with diffusion tensor imaging (DTI) in the corpus
      callosum (CC) and other major fibers. METHODS: Twenty-four patients with SIVD and
      32 with AD were recruited. Four domains of the Neuropsychiatric Inventory (NPI)
      (hyperactivity, psychosis, affective, and apathy) and two DTI parameters
      [fractional anisotropy (FA) and mean diffusivity (MD)] within the genu, body
      (BCC), and splenium (SCC) of the CC and other major fibers were assessed.
      RESULTS: Overall, the patients with clinical dementia rating (CDR) 1 ~ 2 had
      higher scores in apathy domain than those with CDR0.5. Among those with CDR1 ~ 2,
      SIVD had higher scores in apathy domain than AD. MD values in the BCC/SCC were
      positively correlated with total NPI score and psychosis, hyperactivity, and
      apathy domains. FA values in the SCC were inversely correlated with total NPI
      score and psychosis domain. The correlations were modified by age, the CASI, and
      CDR scores. Stepwise linear regression models suggested that FA value within the
      left superior longitudinal fasciculus predicted the hyperactivity domain. MD
      value within the SCC/left uncinate fasciculus and FA value within the GCC/left
      forceps major predicted the psychosis domain. MD value within the right superior
      longitudinal fasciculus and CDR predicted the apathy domain. Further analysis
      suggested distinct patterns of regression models between SIVD and AD patients.
      CONCLUSION: White matter integrity within the BCC/SCC had associations with multi
      domains of BPSD. Our study also identified important roles of regions other than
      the CC to individual domain of BPSD, including the left superior longitudinal
      fasciculus to the hyperactivity domain, the left uncinate fasciculus/forceps
      major to the psychosis domain, and the right superior longitudinal fasciculus to
      the apathy domain. The neuronal substrates in predicting BPSD were different
      between SIVD and AD patients. Of note, apathy, which was more profound in SIVD,
      was associated with corresponding fiber disconnection in line with dementia
      severity and global cognition decline.

PMID- 28754096
TI  - Successful treatment with anti-programmed-death-1 antibody in a relapsed natural
      killer/T-cell lymphoma patient with multi-line resistance: a case report.
AB  - BACKGROUND: Extranodal natural killer/T-cell lymphoma (NKTCL), nasal type, is an
      aggressive malignancy with poor prognosis. Currently, there is no recommended
      standard therapy for relapsed NKTCL. CASE PRESENTATION: A 37-year-old woman with
      lymphadenopathy was diagnosed with NKTCL by biopsy of an enlarged lymph node on
      the right side of her neck. Enhanced computed tomography revealed no metastasis.
      For this patient, we performed continuous chemotherapy followed by radiotherapy;
      however, nodule biopsy showed metastases in her lower limbs 3 months after
      radiotherapy, which confirmed disease progression. Unfortunately, the patient' s
      temperature was persistently high and her skin ulcers could not be controlled
      well using multi-line treatment. Therefore, we attempted treatment with the anti
      programmed-death-1 (PD-1) antibody, pembrolizumab. Surprisingly, the patient
      achieved clinical complete remission (CR) after four cycles of pembrolizumab
      treatment, despite having persistent detectable Epstein-Barr virus (EBV) DNA.
      Other molecular monitoring techniques were unavailable for this patient owing to
      the retrospective nature of the study. The only adverse event was soreness of the
      upper limb joints and muscles. CONCLUSION: This relapsed NKTCL case treated with
      pembrolizumab showed that multimodal therapy including pembrolizumab would be
      partially or totally effective for relapsed NKTCL.

PMID- 28754097
TI  - Lymphangioleiomyomatosis, multifocal micronodular pneumocyte hyperplasia, and
      sarcoidosis: more pathological findings in the same chest CT, or a single
      pathological pathway?
AB  - BACKGROUND: Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome,
      lymphangioleiomyomatosis/tuberous sclerosis complex (LAM-TSC), and sarcoidosis
      are three rare diseases. Here we present, to the best of our knowledge, the first
      description of a patient with the coexistence of these three diseases. CASE
      PRESENTATION: A 47-year-old woman affected by LAM-TSC and primary biliary
      cirrosis/autoimmune hepatitis overlap syndrome. During her follow up a high
      resolution chest CT scan (HRTC) confirmed the presence of both multiple cysts and
      micronodular opacities consistent with multifocal micronodular pneumocytes
      hyperlasia (MMPH), and revealed multiple hilar-mediastinal symmetrical
      lymphadenopathies suggestive of sarcoidosis. Simultaneously, subcutaneous nodules
      appeared on her forearm bilaterally. Cutaneous biopsy showed granulomatous
      dermatitis with sarcoid-like granulomas. A diagnosis of stage I pulmonary
      sarcoidosis was made. No treatment for sarcoidosis was initiated since the
      patient had neither systemic involvement, nor respiratory impairment.
      CONCLUSIONS: The presence of more than one rare disease should challenge the
      concept of a potential common underlying mechanism, since the a priori
      probability of the concomitant presence of different conditions with different
      pathogenic mechanisms - especially if rare diseases - is low. We speculate that
      the dysregulation of the pathway involving mTOR and MAPK and their interaction
      might play a role in the pathogenesis of other diseases, including sarcoidosis.

PMID- 28754098
TI  - Longitudinal shortening remains the principal component of left ventricular
      pumping in patients with chronic myocardial infarction even when the absolute
      atrioventricular plane displacement is decreased.
AB  - BACKGROUND: The majority (60%) of left ventricular (LV) stroke volume (SV) is
      generated by longitudinal shortening causing apical atrioventricular plane
      displacement (AVPD) in systole. The remaining SV is caused by radial inward
      motion of the epicardium both in the septal and the lateral wall. We aimed to
      determine if these longitudinal, septal and lateral contributions to LVSV are
      changed in patients with chronic myocardial infarction (MI). METHODS: Patients
      with a chronic (>3 months) ST-elevation MI in the left anterior descending (LAD,
      n = 20) or right coronary artery (RCA, n = 16) and healthy controls (n = 20) were
      examined with cardiovascular magnetic resonance (CMR). AVPD was quantified in
      long axis cine CMR images and LV volumes and dimensions in short axis cine
      images. RESULTS: AVPD was decreased both in patients with LAD-MI (11 +/- 1 mm, p
      < 0.001) and RCA-MI (13 +/- 1 mm, p < 0.05) compared to controls (15 +/- 0 mm).
      However, the longitudinal contribution to SV was unchanged for both LAD-MI (58 +/
      3%, p = 0.08) and RCA-MI (59 +/- 3%, p = 0.09) compared to controls (64 +/- 2%).
      The preserved longitudinal contribution despite decreased absolute AVPD was a
      results of increased epicardial dimensions (p < 0.01 for LAD-MI and p = 0.06 for
      RCA-MI). In LAD-MI the septal contribution to LVSV was decreased (5 +/- 1%)
      compared to both controls (10 +/- 1%, p < 0.01) and patients with RCA-MIs (10 +/-
      1%, p < 0.01). The lateral contribution was increased in LAD-MI patients (44 +/-
      3%) compared to both RCA-MI (35 +/- 2%, p < 0.05) and controls (29 +/- 2%, p <
      0.001). CONCLUSION: Longitudinal shortening remains the principal component of
      left ventricular pumping in patients with chronic MI even when the absolute AVPD
      is decreased.

PMID- 28754099
TI  - Antioxidant and vasorelaxant activities induced by northeastern Brazilian
      fermented grape skins.
AB  - BACKGROUND: In northeastern Brazil, grape pomace has become a potential
      alternative byproduct because of the recover phenolic compounds from the
      vinification process. Comparative analyses were performed between lyophilized
      extract of grape skins from pomace, described as fermented (FGS), and fresh,
      unfermented (UGS) grape skins to show the relevant brand's composition upon the
      first maceration in winemaking. METHODS: The use of in vitro testing such as
      Folin-Ciocalteu's, DPPH free radical scavenger and HPLC methods were performed to
      evidence antioxidant effect and phenolic compounds. Additionally, vascular
      reactivity studies were performed in third-order branches of rat superior
      mesenteric arteries, which were obtained and placed in organ baths containing
      Krebs-Henseleit solution, maintained at 37  degrees C, gassed with a mixture of
      95% O2 and 5% CO2, and maintained at pH 7.4. The in situ formation of reactive
      oxygen species (ROS) was evaluated in small mesenteric rings using oxidative
      fluorescent dihydroethidium dye. RESULTS: We found higher phenolic content and
      antioxidant activity in FGS when compared to UGS. HPLC analyses identified a
      significant number of phenolic compounds with antioxidant potential in both
      samples. The vasorelaxant effect induced by FGS was more potent than that induced
      by UGS, and the activity was attenuated after removal of vascular endothelium or
      by blockade of endothelium-derived relaxing factors, such as NO and EDHF.
      CONCLUSIONS: The FGS extract may be a great source of natural polyphenol products
      with potent antioxidant effects and endothelium-dependent vasodilatory actions
      involving NO and EDHF pathways.

PMID- 28754100
TI  - Identifying genomic targets for protein over-expression by "omics" analysis of
      Quiescent Escherichia coli cultures.
AB  - BACKGROUND: A cellular stress response is triggered upon induction of recombinant
      protein expression which feedback inhibits both growth as well as protein
      synthesis. In order to separate these two effects, it was decided to study
      "quiescent cultures" which continue to be metabolically active and express
      recombinant proteins even after growth cessation. The idea was to identify and up
      regulate genes which are responsible for protein synthesis in the absence of
      growth. This would ensure that, even if growth were adversely affected post
      induction, there would be no attendant reduction in the protein expression
      capability of the cells. This strategy allowed us to design host strains, which
      did not grow better post induction but had significantly higher levels of protein
      expression. RESULTS: A quiescent Escherichia coli culture, which is able to
      sustain recombinant protein expression in the absence of growth, was analyzed by
      transcriptomic and proteomic profiling. Many genes involved in carbon
      utilization, biosynthesis of building blocks and stress protection were found to
      be up-regulated in the quiescent phase. Analysis of the global regulators showed
      that fis, which tends to get down-regulated as the cells enter stationary phase,
      remained up-regulated throughout the non-growing quiescent phase. The downstream
      genes regulated by fis like carB, fadB, nrfA, narH and queA were also up
      regulated in the quiescent phase which could be the reason behind the higher
      metabolic activity and protein expression ability of these non-growing cells. To
      test this hypothesis, we co-expressed fis in a control culture expressing
      recombinant L-asparaginase and observed a significantly higher buildup of L
      asparaginase in the culture medium. CONCLUSIONS: This work represents an
      important breakthrough in the design of a superior host platform where a gene not
      directly associated with protein synthesis was used to generate a phenotype
      having higher protein expression capability. Many alternative gene targets were
      also identified which may have beneficial effects on expression ability.

PMID- 28754101
TI  - Herbal formula SC-E1 suppresses lipopolysaccharide-stimulated inflammatory
      responses through activation of Nrf2/HO-1 signaling pathway in RAW 264.7
      macrophages.
AB  - BACKGROUND: SC-E1 is a novel herbal formula consisting of five oriental medicinal
      herbs used frequently in traditional herbal medicine for the treatment of
      inflammatory diseases in Korea. This study examined the effects of SC-E1 on
      lipopolysaccharide (LPS)-stimulated macrophages and the molecular mechanism
      involved. METHODS: The cytotoxic effect of the SC-E1 extract was evaluated in RAW
      264.7 cells by MTT assay. The effects of SC-E1 on the free radical scavenging and
      generation of intracellular reactive oxygen species were measured using DPPH and
      DCFH-DA, respectively. The effects of SC-E1 on the production of pro-inflammatory
      cytokines, inflammatory mediators, and related products were determined by ELISA
      and western blotting. The molecular mechanism and the nuclear translocation of
      nuclear factor-kappa B (NF-kappaB) and NF-E2-related factor 2 (Nrf2) were
      examined by western blot analysis and immunocytochemistry. RESULTS: SC-E1
      exhibited strong anti-oxidant activity and inhibited LPS-induced NO secretion as
      well as iNOS expression and the production of pro-inflammatory cytokines, without
      affecting the cell viability. SC-E1 also suppressed the LPS-induced NF-kappaB
      activation and the mitogen-activated protein kinase (MAPK) pathway. Moreover, SC
      E1 induced heme oxygenase-1 (HO-1) expression via the nuclear translocation of
      Nrf2. The inhibitory effects of SC-E1 on the production of pro-inflammatory
      cytokines were abrogated by treatment with SnPP, an HO-1 inhibitor. CONCLUSION:
      These results suggest that SC-E1 exerts its anti-oxidant and anti-inflammatory
      effects through the inhibition of NF-kappaB and MAPK as well as Nrf2-mediated HO
      1 induction in macrophages. These findings provide evidences for SC-E1 to be
      considered as a new prescription for treating inflammatory diseases.

PMID- 28754102
TI  - How active are women who play bingo: a cross-sectional study from the Well!Bingo
      project.
AB  - BACKGROUND: The benefits of physical activity are well established, yet large
      numbers of people are not sufficiently active to gain health benefits. Certain
      population groups are less physically active than others, including older women
      from areas of high economic deprivation. The Well!Bingo project was established
      with the aim of engaging such women in the development of a health promotion
      intervention in a bingo club. This paper reports on the assessment of health
      status, physical activity and sedentary behaviour of women attending a bingo club
      in central Scotland, UK as part of the Well!Bingo project. METHODS: Women
      attending the bingo club were invited to provide information on demographic
      characteristics, and self-reported physical activity and sedentary behaviour via
      a self-complete questionnaire as part of a cross-sectional study (n = 151). A sub
      sample (n = 29) wore an accelerometer for an average of 5.7 +/- 1.4 days.
      Differences between younger (under 60 years) and older adults (60 years and over)
      were assessed using a chi-square test for categorical data and the independent
      samples t-test was used to assess continuous data (p < 0.05). RESULTS: The mean
      age was 56.5 +/- 17.7 years, with 57% living in areas of high deprivation
      (Scottish Index of Multiple Deprivation quintile one and two). Sixty-three
      percent of women (n = 87) reported they were meeting physical activity
      guidelines. However, objective accelerometer data showed that, on average, only
      18.1 +/- 17.3 min a day were spent in moderate to vigorous physical activity.
      Most accelerometer wear time was spent sedentary (9.6 +/- 1.7 h). For both self
      report and accelerometer data, older women were significantly less active and
      more sedentary than younger women. On average, older women spent 1.8 h more than
      younger women in sedentary activities per day, and took part in 21 min less
      moderate to vigorous physical activity (9.4 mins per day). CONCLUSION: The
      findings of this study suggest that bingo clubs are settings that attract women
      from areas of high deprivation and older women in bingo clubs in particular would
      benefit from interventions to target their physical activity and sedentary
      behaviour. Bingo clubs may therefore be potential intervention settings in which
      to influence these behaviours.

PMID- 28754103
TI  - Similar polysomnographic pattern in primary insomnia and major depression with
      objective insomnia: a sign of common pathophysiology?
AB  - BACKGROUND: Our aim is to verify empirically the existence of a major depressed
      subgroup with a similar polysomnographic pattern as primary insomnia, including
      at rapid eye movement sleep level. METHODS: The polysomnographic data from 209
      untreated individuals (30 normative, 84 primary insomnia sufferers, and 95 major
      depressed patients with objective insomnia) who were recruited retrospectively
      from the Erasme hospital database were studied for the whole night and thirds of
      the night. RESULTS: Primary insomnia sufferers and major depressed patients with
      objective insomnia exhibit a similar polysomnographic pattern both for the whole
      night (excess of wake after sleep onset, deficit in slow-wave sleep/rapid eye
      movement sleep, and non-shortened rapid eye movement latency) and thirds of the
      night (excess of wake after sleep onset at first and last third, deficit in slow
      wave sleep in first third, and deficit in rapid eye movement sleep in first and
      last third), including at rapid eye movement sleep level. CONCLUSION: In our
      study, we demonstrated that major depressed patients with objective insomnia
      showed a similar polysomnographic pattern as primary insomnia, including at rapid
      eye movement sleep level, which supports the hypothesis of a common
      pathophysiology that could be hyperarousal. This opens new avenues for
      understanding the pathophysiology of major depression with objective insomnia.

PMID- 28754104
TI  - Syphilis and HIV prevalence and associated factors to their co-infection,
      hepatitis B and hepatitis C viruses prevalence among female sex workers in
      Rwanda.
AB  - BACKGROUND: Human Immunodeficiency Virus (HIV), syphilis, Hepatitis B Virus (HBV)
      and Hepatitis C Virus (HCV) are sexually transmitted infections (STIs) and share
      modes of transmission. These infections are generally more prevalent among female
      sex workers (FSWs). METHODS: This is a cross-sectional study conducted among
      female sex workers (FSWs) in Rwanda in 2015. Venue-Day-Time (VDT) sampling method
      was used in recruiting participants. HIV, syphilis, HBV, and HCV testing were
      performed. Descriptive analyses and logistic regression models were computed.
      RESULTS: In total, 1978 FSWs were recruited. The majority (58.5%) was aged
      between 20 and 29 years old. Up to 63.9% of FSWs were single, 62.3% attained
      primary school, and 68.0% had no additional occupation beside sex work. Almost
      all FSWs (81.2%) had children. The majority of FSWs (68.4%) were venue-based, and
      most (53.5%) had spent less than five years in sex work. The overall prevalence
      of syphilis was 51.1%; it was 2.5% for HBV, 1.4% for HCV, 42.9% for HIV and 27.4%
      for syphilis/HIV co-infection. The prevalence of syphilis, HIV, and syphilis +
      HIV co-infection was increasing with age and decreasing with the level of
      education. A positive association with syphilis/HIV co-infection was found in: 25
      years and older (aOR = 1.82 [95% CI:1.33-2.50]), having had a genital sore in the
      last 12 months (aOR = 1.34 [95% CI:1.05-1.71]), and having HBsAg-positive test
      (aOR = 2.09 [1.08-4.08]). CONCLUSION: The prevalence of HIV and syphilis
      infections and HIV/syphilis co-infection are very high among FSWs in Rwanda. A
      strong, specific prevention program for FSWs and to avert HIV infection and other
      STIs transmission to their clients is needed.

PMID- 28754105
TI  - GIT1 gene deletion delays chondrocyte differentiation and healing of tibial
      plateau fracture through suppressing proliferation and apoptosis of chondrocyte.
AB  - BACKGROUND: Although tibial plateau fracture is an uncommon injury, its
      regulation is challenging and there are some influencing factors, including the
      effects of severe bone displacement, depression and cancellous bone cartilage,
      and inevitable cartilage damage. And GIT1 plays an important role in bone mass
      and 78 osteoblast cell migration. METHODS: The study used 72 C57/BL6 mice. A
      tibial plateau fracture model was established by using mice with the same number
      of GIT1 gene deletions (the experimental group) and their wild-type littermates
      (the control group). Joint and bone callus recovery were evaluated by X-ray and
      CT thin layer scans. Micro CT assay and histomorphometry were conducted in order
      to evaluate the volume of newly formed blood vessels. Type II collagen expression
      in tibial tissues after tibial plateau fracture were detected by
      immunohistochemistry after 7, 14 and 21 days. The number of proliferating cell
      nuclear antigen (PCNA) positive cells after tibial plateau fracture was tested by
      immunohistochemistry after 14 and 21 days. The terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining was conducted
      after 14 and 21 days in order to test chondrocyte apoptosis in tibial tissues
      after tibial plateau fracture. RESULTS: The GIT1 gene deletion group mice spent
      less time on the rotating rod than the control group mice (P < 0.05). Compared
      with the control group, postoperative recovery was retarded, because GIT1 gene
      deletion slowed down neovascularization after tibial plateau fracture (P < 0.05).
      Compared with the control group, mouse type II collagen expression significantly
      decreased in the GIT1 gene deletion group, and the proportion of PCNA positive
      cells significantly decreased (P < 0.05). The TUNEL results indicate that GIT1
      gene deletion led to reduced chondrocyte apoptosis. CONCLUSION: GIT1 gene
      deletion can inhibit chondrocyte proliferation and apoptosis during the recovery
      of tibial plateau fracture, so as to delay chondrocyte differentiation and tibial
      plateau fracture healing.

PMID- 28754106
TI  - Retesting and repeat positivity following diagnosis of Chlamydia trachomatis and
      Neisseria gonorrhoea in New Zealand: a retrospective cohort study.
AB  - BACKGROUND: Testing for reinfection at 3 to 6 months following treatment for
      Chlamydia Trachomatis or Neisseria gonorrhoea is recommended in best practice
      sexual health management guidelines. This study aimed to describe rates of
      retesting and repeat positivity following diagnosis of chlamydia or gonorrhoea in
      a defined geographic region of New Zealand. METHODS: Retrospective cohort study
      in Wellington, New Zealand involving analysis of laboratory data for chlamydia
      and gonorrhoea tests performed in primary care and sexual health clinics (July
      2012-July 2015). OUTCOME MEASURES: rate of retesting and rate of repeat
      positivity 6 weeks to 6 months after a positive result (index event). Kaplan
      Meier curves were used to plot time from first index event to retest. Logistic
      regression modelling was used to determine the odds of retesting and repeat
      positivity between 6 weeks and 6 months of follow-up, adjusting for potential
      confounders (age, gender, ethnicity and socioeconomic deprivation). RESULTS:
      Overall 29.4% (1919/6530) of the cohort was retested between 6 weeks and 6
      months, with 18% (347/1919) of those retested returning positive results. Lower
      odds of retesting were observed for males (OR 0.4, 95% CI 0.34-0.48), and
      individuals of NZ Maori (OR 0.72, 0.61-0.85) and Pacific ethnicities (OR 0.49,
      0.39-0.62, reference European). Factors associated with higher odds of repeat
      positivity on retesting included male gender (OR 2.0, 1.14-2.82), age 15-19 years
      (OR 1.78, 1.32-2.41, reference 20-24 years), chlamydia/gonorrhoea co-infection
      (OR 2.39, 1.32-4.35, reference chlamydia only), Maori (OR 1.6, 1.18-2.17) and
      Pacific ethnicities (OR 1.88, 1.22-2.9, reference European). CONCLUSIONS: We
      observed low adherence to STI retesting guidelines, and marked gender and ethnic
      disparities in rates of retesting and repeat positivity. Low retesting rates are
      suggestive of low levels of awareness of this aspect of patient management, and
      an absence of a systematic approach to retesting. High rates of repeat positivity
      reinforce the importance of advising patients about reducing their risk of
      reinfection, including notification and treatment of all recent sexual partners.
      Greater priority needs to be placed on increasing retesting and reducing rates of
      reinfection, with strategies implemented to improve these important aspects of
      patient care and population STI control.

PMID- 28754107
TI  - Interaction between obesity and the Hypoxia Inducible Factor 3 Alpha Subunit
      rs3826795 polymorphism in relation with plasma alanine aminotransferase.
AB  - BACKGROUND: Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) DNA has been
      demonstrated to be associated with obesity in the methylation level, and it also
      has a Body Mass Index (BMI)-independent association with plasma alanine
      aminotransferase (ALT). However, the relation among obesity, plasma ALT, HIF3A
      polymorphism and methylation remains unclear. This study aims to identify the
      association between HIF3A polymorphism and plasma ALT, and further to determine
      whether the effect of HIF3A polymorphism on ALT could be modified by obesity or
      mediated by DNA methylation. METHODS: The HIF3A rs3826795 polymorphism was
      genotyped in a case-control study including 2030 Chinese children aged 7-18 years
      (705 obese cases and 1325 non-obese controls). Furthermore, the HIF3A DNA
      methylation of the peripheral blood was measured in 110 severely obese children
      and 110 age- and gender- matched normal-weight controls. RESULTS: There was no
      overall association between the HIF3A rs3826795 polymorphism and ALT. A
      significant interaction between obesity and rs3826795 in relation with ALT was
      found (P inter = 0.042), with rs3826795 G-allele number elevating ALT
      significantly only in obese children (beta' = 0.075, P = 0.037), but not in non
      obese children (beta' = -0.009, P = 0.741). Additionally, a mediation effect of
      HIF3A methylation was found in the association between the HIF3A rs3826795
      polymorphism and ALT among obese children (beta' = 0.242, P = 0.014). CONCLUSION:
      This is the first study to report the interaction between obesity and HIF3A gene
      in relation with ALT, and also to reveal a mediation effect among the HIF3A
      polymorphism, methylation and ALT. This study provides new evidence to the
      function of HIF3A gene, which would be helpful for future risk assessment and
      personalized treatment of liver diseases.

PMID- 28754108
TI  - A reversed gender pattern? A meta-analysis of gender differences in the
      prevalence of non-suicidal self-injurious behaviour among Chinese adolescents.
AB  - BACKGROUND: A reversed gender pattern has been observed in the suicide rate in
      China compared to elsewhere. Like suicidal behaviour, non-suicidal self-injurious
      (NSSI) behaviour is a health-risk behaviour. We examined whether a reversed
      gender pattern existed in the prevalence of NSSI. METHODS: Online literature
      databases were searched for English and Chinese articles on NSSI behaviours among
      the Chinese. A meta-analysis with a random-effects model and a subgroup analysis
      were used to estimate the odds ratios of gender differences in NSSI prevalence
      among Chinese adolescents including college students, middle school students, and
      clinical samples, as well as rural, urban, and Hong Kong middle school students.
      RESULTS: There was a male bias in NSSI prevalence among college students (OR =
      1.56, 95% CI = [1.30, 1.87], p < 0.001), and a female bias among middle school
      students (OR = 0.83, 95% CI = [0.73, 0.94], p < 0.01), but there was no gender
      difference among clinical samples (OR = 0.88, 95% CI = [0.41, 1.89], p > 0.1).
      The NSSI prevalence among middle school students had a female bias in the rural
      (OR = 0.58, 95% CI = [0.47, 0.72], p < 0.001) and Hong Kong areas (OR = 0.91, 95%
      CI = [0.86, 0.96], p < 0.001), with the gender difference in NSSI prevalence in
      the Hong Kong areas being greater than in rural areas. No gender difference in
      NSSI prevalence was found in urban areas (OR = 1.01, 95% CI = [0.84, 1.22], p >
      0.1) among middle school students. CONCLUSIONS: Our analysis indicated the
      existence of specific gender and age patterns in NSSI prevalence among Chinese
      adolescents. The sample type, age, and the areas that have different gender norms
      and culture could partly explain this pattern.

PMID- 28754109
TI  - Prognostic value of total tumor volume in patients with nasopharyngeal carcinoma
      treated with intensity-modulated radiotherapy.
AB  - BACKGROUND: Few studies have evaluated the prognostic value of total tumor volume
      (TTV), which reflects both the primary tumor volume and nodal tumor volume, in
      NPC. Furthermore, the relationship between TTV and survival remains unknown. The
      purpose of this study was to evaluate the prognostic value of TTV in patients
      with NPC treated with intensity-modulated radiation therapy (IMRT). METHODS: TTV
      was retrospectively assessed in 455 patients with newly diagnosed, non-metastatic
      NPC. All patients were treated using IMRT; 91.1% (288/316) of patients with stage
      III-IVb also received cisplatin-based chemotherapy. Receiver operating
      characteristic (ROC) curves were used to identify the optimal TTV cut-off point
      and examine the prognostic value of combined TTV with current clinical stage.
      RESULTS: Mean TTV was 11.1 cm3 (range, 0.3-27.9 cm3) in stage I, 22.5 cm3 (1.3
      92.4 cm3) in stage II, 40.6 cm3 in stage III (3.2-129.2 cm3), and 77.5 cm3 in
      stage IVa-b (7.1-284.1 cm3). For all patients, the 4-year estimated FFS, OS,
      DMFS, and LRRFS rates for patients with a TTV <= 28 vs. > 28 cm3 were 93 vs.
      71.4% (P < 0.001), 95.1 vs. 75.4% (P < 0.001), 94.5 vs. 79.4% (P < 0.001), and
      96.2 vs. 88% (P = 0.001). TTV was an independent prognostic factor for FFS, OS,
      DMFS and LRRFS in all patients. In stage III-IVb, 4-year estimated FFS, OS, DMFS,
      and LRRFS for a TTV <=28 vs. >28 cm3 were 88.9 vs. 70.5% (P = 0.001), 96.2 vs.
      72.7% (P < 0.001), 91.2 vs. 78.3% (P = 0.008), and 93.8 vs. 87.6% (P = 0.063).
      TTV was an independent prognostic factor for FFS, OS and DMFS in stage III-IVb.
      Receiver operating characteristic (ROC) curve analysis curves revealed adding TTV
      to clinical stage had superior prognostic value for treatment failure compared to
      clinical stage alone (P = 0.016). CONCLUSIONS: TTV is an important prognosticator
      for treatment outcome and significantly improves the prognostic value of the
      current staging system for patients with NPC treated with IMRT.

PMID- 28754110
TI  - Predictors of health care drop-out in an inception cohort of patients with early
      onset rheumatoid arthritis.
AB  - BACKGROUND: RA patients who eventually dropped out of treatment and out of the
      health care system had potentially disastrous consequences for their health
      related quality-of-life outcomes. Objectives of the study were to identify
      predictors of health care drop out (HDO) in an inception and ongoing cohort of
      patients with recent onset RA. METHODS: Charts from patients attending an early
      arthritis clinic from February 2004 to December 2015, and standardized follow-up
      evaluations were reviewed. Patients with HDO (cases) were defined when they did
      not return back to the clinic for a schedule visit for at least one year.
      Persistence with therapy was defined as length of time patients complied with RA
      treatment. A case-control nested within a cohort design was used to compare
      baseline and cumulative (up to HDO or equivalent follow-up) variables between
      cases and paired controls (patients compliant with scheduled visits). Cox
      regression analysis was used to investigate predictors of HDO. The study was
      approved by the Institutional Review Board and patients gave written informed
      consent to have their data published. RESULTS: Data from 170 patients (89.4%
      female, [mean+/-SD] age: 38.2+/-12.6 years) with >=1 year of follow-up were
      analyzed; up to December 2015, (median, interquartile rage) follow-up was 86.6
      months (43.2-123) during which 35 (20.6%) patients had HDO after 41.1 months
      (12.1-58.7). Baseline and cumulative variables related to disease activity,
      treatment and persistence with therapy entered regression models; cumulative
      number of flares, number of disease-modifying anti-rheumatic drugs /patient and
      persistence <50% emerged as predictors of HDO. Five cases returned back after
      (median, range) drop out time of 3.8 years (2.3-5.8); they exhibited higher
      disability and poorer function than paired controls and outcomes were sustained
      up to their last follow-up. CONCLUSIONS: In a real clinical setting of an EAC,
      failure to control disease activity, intensive treatment and poor persistence
      with therapy predicted HDO. Abandonment of health care had a negative impact on
      patient outcomes and was sustained even after health care was reinitiated.

PMID- 28754111
TI  - Care of the mother-infant dyad: a novel approach to conducting and evaluating
      neonatal resuscitation simulation training in Bihar, India.
AB  - BACKGROUND: As the global under-five mortality rate declines, an increasing
      percentage is attributable to early neonatal mortality. A quarter of early
      neonatal deaths are due to perinatal asphyxia. However, neonatal resuscitation
      (NR) simulation training in low-resource settings, where the majority of neonatal
      deaths occur, has achieved variable success. In Bihar, India, the poorest region
      in South Asia, there is tremendous need for a new approach to reducing neonatal
      morality. METHODS: This analysis aims to assess the impact of a novel in-situ
      simulation training program, developed by PRONTO International and implemented in
      collaboration with CARE India, on NR skills of nurses in Bihar. Skills were
      evaluated by clinical complexity of the simulated scenario, which ranged from
      level 1, requiring NR without a maternal complication, to level 3, requiring
      simultaneous management of neonatal and maternal complications. A total of 658
      nurses at 80 facilities received training 1 week per month for 8 months.
      Simulations were video-recorded and coded for pre-defined clinical skills using
      StudiocodeTM. RESULTS: A total of 298 NR simulations were analyzed. As simulation
      complexity increased, the percentage of simulations in which nurses completed key
      steps of NR did not change, even with only 1-2 providers in the simulation. This
      suggests that with PRONTO training, nurses were able to maintain key skills
      despite higher clinical demands. As simulation complexity increased from level 1
      to 3, time to completion of key NR steps decreased non-significantly. Median time
      to infant drying decreased by 7.5 s (p = 0.12), time to placing the infant on the
      warmer decreased by 21.7 s (p = 0.27), and time to the initiation of positive
      pressure ventilation decreased by 20.8 s (p = 0.12). Nevertheless, there remains
      a need for improvement in absolute time elapsed between delivery and completion
      of key NR tasks. CONCLUSIONS: PRONTO simulation training enabled nurses in Bihar
      to maintain core NR skills in simulation despite demands for higher-level triage
      and management. Although further evaluation of the PRONTO methodology is
      necessary to understand the full scope of its impact, this analysis highlights
      the importance of conducting and evaluating simulation training in low-resource
      settings based on simultaneous care of the mother-infant dyad.

PMID- 28754112
TI  - Pharmacokinetics, bioavailability and dose assessment of Cefquinome against
      Escherichia coli in black swans (Cygnus atratus).
AB  - BACKGROUND: The objective of this study is to investigate pharmacokinetics and
      dose regimens of cefquinome in black swans following intravenous (IV) and
      intramuscular (IM) administration at a single dose of 2 mg/kg. The MICs of
      cefquinome against 49 Escherichia coli isolates from black swans were determined.
      Monte Carlo simulation was applied to conduct the dose regimen assessment and
      optimization of cefquinome against E. coli in black swans, and a
      pharmacokinetic/pharmacodynamic (PK/PD) cutoff was established for E. coli
      isolates obtained in this study. RESULTS: The PK parameters of T1/2alpha (0.31
      h), T1/2beta (1.69 h) and ClB (0.13 L/kg.h) indicated a rapid distribution and
      elimination of cefquinome in black swans after IV administration. After IM
      injection, the corresponding PK parameters of T1/2Ka, T1/2Ke, Tmax, Cmax, and F
      were 0.12 h, 1.62 h, 0.39 h, 5.71 MUg/mL and 74.2%, respectively. The MICs of
      cefquinome against black swans E. coli ranged from 0.03 to 8 MUg/mL, with MIC50
      and MIC90 of 0.06 and 0.5 MUg/mL, respectively. The PK/PD cutoff of cefquinome
      against E. coli was determined to be 0.2 MUg/mL. Monte Carlo simulation showed
      that the nominal dose regimen (2 mg/kg/24 h) could not achieve a satisfactory
      probability of target attainment (PTA) for %TMIC >= 50%, indicating a risk of
      treatment failure and the development of potential drug resistance. CONCLUSIONS:
      The current daily dosage of cefquinome when divided into 12-h interval (1
      mg/kg/12 h) may be effective for the treatment of E. coli infections with an MIC
      <=0.5 MUg/mL.

PMID- 28754113
TI  - Progress in coverage of bed net ownership and use in Burkina Faso 2003-2014:
      evidence from population-based surveys.
AB  - BACKGROUND: Use of insecticide-treated bed nets (ITNs) is the cornerstone of
      malaria prevention. In 2010 and 2013, the Burkina Faso Government launched mass
      distribution campaigns of ITNs to increase coverage of ownership and use in the
      country. This study assessed the progress towards universal bed net coverage in
      Burkina Faso. METHODS: The authors used data from the Burkina Faso 2003 and 2010
      Demographic and Health Surveys (DHS), the 2006 Multiple Indicator Cluster Surveys
      (MICS) and the 2014 Malaria Indicator Survey (MIS). For each survey, the authors
      computed key malaria prevention indicators in line with recommendations from the
      Survey and Indicator Task Force of the Roll Back Malaria Monitoring and
      Evaluation Reference Group. The trends over a decade was assessed by calculating
      percentage point change between 2003 and 2014. RESULTS: At national level, the
      proportion of households owning at least one ITN increased substantially from
      5.6, 95% CI (4.7, 6.5%) in 2003 to 89.9% (88.5, 91.2%) in 2014, with low
      heterogeneity between regions. The proportion of households owning at least one
      ITN per two people increased significantly from 1.8% (1.4, 2.3%) in 2003 to 49.2%
      (47.3, 51.0%) in 2014. ITN use in the general population increased from 2.0%
      (1.6, 2.3%) in 2003, to 67.0% (65.3, 68.7%) in 2014. A similar trend was observed
      among children under the age of  five years, increasing from 1.9% (1.5, 2.4%) in
      2003 to 75.2% (73.2, 77.3%) in 2014, and among pregnant women, increasing from
      3.0% (1.9, 4.2%) in 2003 to 77.1% (72.9, 81.3%) in 2014. The intra-household
      ownership gap was 67.0% (61.5, 72.4%) in 2003, but decreased significantly to
      45.3% (43.6, 47.1%) in 2014. The behavioural gap, which was relatively low in
      2013 with only 20.0% of people who had access to an ITN but were not using it,
      further decreased to 5.9% in 2014. CONCLUSION: Burkina Faso made considerable
      progress in coverage of ITN ownership, access and use between 2003 and 2014, as a
      result of the two free mass distribution campaigns in 2010 and 2013. However, ITN
      coverage remains below the national targets of 100% for ownership and 80% for
      use. The results of 90% of ownership and 67% of use confirm that free mass
      distribution campaigns of ITNs are effective; however, there is room for
      improvement to reach and maintain optimal coverage of ITN ownership and use.

PMID- 28754114
TI  - The effect of different screw-rod design on the anti-rotational torque: a
      biomechanical comparison of three conventional screw-rod constructs.
AB  - BACKGROUND: Screw-rod constructs have been widely used to correct spinal
      deformities, but the effects of different screw-rod systems on anti-rotational
      torque have not been determined. This study aimed to analyze the biomechanical
      effect of different rod-screw constructs on anti-rotational torque. METHODS:
      Three conventional spinal screw-rod systems (Legacy, RF-F-10 and USSII) were used
      to test the anti-rotational torque in the material test machine. ANOVA was
      performed to evaluate the anti-rotational capacity of different pedicle screws
      rod constructs. RESULTS: The anti-rotational torque of Legacy group, RF-F-10
      group and USSII group were 12.3 +/- 1.9 Nm, 6.8 +/- 0.4 Nm, and 3.9 +/- 0.8 Nm,
      with a P value lower than 0.05. This results indicated that the Legacy screws-rod
      construct could provide a highest anti-rotation capacity, which is 68% and 210%
      greater than RF-F-10 screw-rod construct and USSII screw-rod respectively.
      CONCLUSIONS: The anti-rotational torque may be mainly affected by screw cap and
      groove design. Our result showed the anti-rotational torque are: Legacy system >
      RF-F-10 system > USSII system, suggesting that appropriate rod-screw constructs
      selection in surgery may be vital for anti-rotational torque improvement and
      preventing derotation correction loss.

PMID- 28754115
TI  - In vivo plug-and-play: a modular multi-enzyme single-cell catalyst for the
      asymmetric amination of ketoacids and ketones.
AB  - BACKGROUND: Transaminases have become a key tool in biocatalysis to introduce the
      amine functionality into a range of molecules like prochiral alpha-ketoacids and
      ketones. However, due to the necessity of shifting the equilibrium towards the
      product side (depending on the amine donor) an efficient amination system may
      require three enzymes. So far, this well-established transformation has mainly
      been performed in vitro by assembling all biocatalysts individually, which comes
      along with elaborate and costly preparation steps. We present the design and
      characterization of a flexible approach enabling a quick set-up of single-cell
      biocatalysts producing the desired enzymes. By choosing an appropriate co
      expression strategy, a modular system was obtained, allowing for flexible plug
      and-play combination of enzymes chosen from the toolbox of available
      transaminases and/or recycling enzymes tailored for the desired application.
      RESULTS: By using a two-plasmid strategy for the recycling enzyme and the
      transaminase together with chromosomal integration of an amino acid
      dehydrogenase, two enzyme modules could individually be selected and combined
      with specifically tailored E. coli strains. Various plug-and-play combinations of
      the enzymes led to the construction of a series of single-cell catalysts suitable
      for the amination of various types of substrates. On the one hand the
      fermentative amination of alpha-ketoacids coupled both with metabolic and non
      metabolic cofactor regeneration was studied, giving access to the corresponding
      alpha-amino acids in up to 96% conversion. On the other hand, biocatalysts were
      employed in a non-metabolic, "in vitro-type" asymmetric reductive amination of
      the prochiral ketone 4-phenyl-2-butanone, yielding the amine in good conversion
      (77%) and excellent stereoselectivity (ee = 98%). CONCLUSIONS: The described
      modularized concept enables the construction of tailored single-cell catalysts
      which provide all required enzymes for asymmetric reductive amination in a
      flexible fashion, representing a more efficient approach for the production of
      chiral amines and amino acids.

PMID- 28754116
TI  - How is disease severity associated with quality of life in psoriasis patients?
      Evidence from a longitudinal population-based study in Sweden.
AB  - BACKGROUND: Assessing the impact of disease severity on generic quality of life
      (QOL) is a critical step in outcomes research and in the development of decision
      analytic models structured around health states defined by clinical measures.
      While data from routine clinical practice found in healthcare registers are
      increasingly used for research, more attention should be paid to understanding
      the relationship between clinical measures of disease severity and QOL. The
      purpose of this work was therefore to investigate this relationship in psoriasis
      using a population-based dataset. METHODS: Severity was measured by the Psoriasis
      Area and Severity Index (PASI), which combines severity of erythema, induration,
      and desquamation into a single value ranging from 0 to 72. The generic EQ-5D-3L
      utility instrument, under the UK tariff, was used to measure QOL. The association
      between PASI and EQ-5D-3L was estimated using a population-based dataset of 2674
      patients with moderate to severe psoriasis enrolled over ten years in the Swedish
      psoriasis register (PsoReg). Given the repeated measurement of patients in the
      register data, a longitudinal fixed-effects model was employed to control for
      unobserved patient-level heterogeneity. RESULTS: Marginal changes in PASI are
      associated with a non-linear response in EQ-5D-3L: Moving from PASI 10 to 9 (1 to
      0) is associated with an increase of 0.0135 (0.0174) in EQ-5D-3L. Furthermore,
      unobserved patient-level heterogeneity appears to be an important source of
      confounding when estimating the relationship between QOL and PASI. CONCLUSIONS:
      Using register data to estimate the impact of disease severity on QOL while
      controlling for unobserved patient-level heterogeneity shows that PASI appears to
      have a larger impact on QOL than previously estimated. Routine collection of
      generic QOL data in registers should be encouraged to enable similar applications
      in other disease areas. TRIAL REGISTRATION: Not applicable.

PMID- 28754117
TI  - Differences in primary health care use among sub-Saharan African immigrants in
      Norway: a register-based study.
AB  - BACKGROUND: Immigrants' utilization of primary health care (PHC) services differs
      from that of the host populations. However, immigrants are often classified in
      broad groups by continent of origin, and the heterogeneity within the same
      continent may hide variation in use among immigrant groups at a national level.
      Differences in utilization of PHC between sub-Saharan African immigrants have not
      received much attention. METHODS: Registry-based study using merged data from the
      National Population Register and the Norwegian Health Economics Administration.
      African immigrants and their descendants registered in Norway in 2008 (36,366
      persons) where included in this study. Using chi2 test and logistic regression
      models, we assessed the differences in the use of PHC, including general
      practitioner (GP) and emergency room (ER) services, and the distribution of
      morbidity burden for immigrants from Somalia, Ethiopia, Eritrea, and Gambia. For
      the analyses, we used the number of visits and medical diagnoses from each
      consultation registered by the physician. RESULT: Among the total studied
      population, 66.1% visited PHC within 1 year. The diagnoses registered were
      similar for all four immigrants groups, regardless of country of origin. Compared
      to immigrants from Somalia, the age and sex adjusted odds ratios (OR) for use of
      GP were significantly lower for Ethiopians (OR 0.91; 0.86-0.97), Eritreans (OR
      0.85; 0.79-0.91), and Gambians (OR 0.88; 0.80-0.97). Similarly, we also observed
      lower use of ER among Ethiopians (OR 0.88; 0.81-0.95), Eritreans (OR 0.56; 0.51
      0.62) and Gambians (OR 0.81; 0.71-0.92). However, immigrants from Somalia reduced
      their use of PHC with longer duration of stay in Norway. Differences between
      groups persisted after further adjustment for employment status. CONCLUSION:
      Despite the similarities in diagnoses among the sub-Saharan African immigrant
      groups in Norway, their use of PHC services differs by country of origin and
      length of stay. It is important to assess the reasons for the differences in
      these groups to identify barriers and facilitators to access to healthcare for
      future interventions.

PMID- 28754118
TI  - Anticoagulation with warfarin and rivaroxaban ameliorates experimental autoimmune
      encephalomyelitis.
AB  - BACKGROUND: In multiple sclerosis, coagulation factors have been shown to
      modulate inflammation. In this translational study, we investigated whether long
      term anticoagulation with warfarin or rivaroxaban has beneficial effects on the
      course of autoimmune experimental encephalomyelitis (EAE). METHODS: Female SJL/J
      mice treated with anticoagulants namely warfarin or rivaroxaban were immunized
      with PLP139-151. Stable anticoagulation was maintained throughout the entire
      experiment. Mice without anticoagulation treated with the vehicle only were used
      as controls. The neurological deficit was recorded during the course of EAE, and
      histopathological analyses of inflammatory lesions were performed. RESULTS: In
      preventive settings, both treatment with warfarin and rivaroxaban reduced the
      maximum EAE score as compared to the control group and led to a reduction of
      inflammatory lesions in the spinal cord. In contrast, therapeutic treatment with
      warfarin had no beneficial effects on the clinical course of EAE. Signs of
      intraparenchymal hemorrhage at the site of the inflammatory lesions were not
      observed. CONCLUSION: We developed long-term anticoagulation models that allowed
      exploring the course of EAE under warfarin and rivaroxaban treatment. We found a
      mild preventive effect of both warfarin and rivaroxaban on neurological deficits
      and local inflammation, indicating a modulation of the disease induction by
      anticoagulation.

PMID- 28754119
TI  - Effect of a herbal extract powder (YY-312) from Imperata cylindrica Beauvois,
      Citrus unshiu Markovich, and Evodia officinalis Dode on body fat mass in
      overweight adults: a 12-week, randomized, double-blind, placebo-controlled,
      parallel-group clinical trial.
AB  - BACKGROUND: YY-312 is a herbal extract powder from Imperata cylindrica Beauvois,
      Citrus unshiu Markovich, and Evodia officinalis Dode, which have health promoting
      effects, including body fat reduction. We aimed to evaluate the efficacy and
      safety of YY-312 for body fat reduction in overweight adults. METHODS: This was a
      12-week, randomized, double-blind, placebo-controlled, parallel-group clinical
      trial performed in overweight Korean adults aged 19-60 years with a body mass
      index of 25.0-29.9 kg/m2. The daily dose of YY-312 was 2400 mg (containing 1800
      mg of active herbal extract and 600 mg of cyclodextrin). Primary outcomes were
      reductions in body fat mass (BFM) and body fat percentage (BF%) after 12 weeks.
      Secondary outcomes included reductions in body weight and waist circumference
      (WC) after 12 weeks. RESULTS: After 12 weeks, BFM (1.6 kg vs. 0.1 kg; P = 0.023)
      and BF% (1.5% vs. -0.2%; P = 0.018) decreased significantly more in the YY-312
      group than in the placebo group, as did body weight (2.7 kg vs. 1.0 kg; P =
      0.014) and WC (2.2 cm vs. 0.8 cm; P = 0.049). All safety parameters were within
      normal limits; no serious adverse events occurred in either group. CONCLUSIONS:
      In a 12-week clinical trial in overweight adults, YY-312 resulted in
      significantly greater reduction in body fat vs. placebo, while being safe and
      well tolerated. TRIAL REGISTRATION: cris.nih.go.kr: ( KCT0001225 ).

PMID- 28754120
TI  - Nano-based delivery of RNAi in cancer therapy.
AB  - BACKGROUND: RNA interference (RNAi), a newly developed method in which RNA
      molecules inhibit gene expression, has recently received considerable research
      attention. In the development of RNAi-based therapies, nanoparticles, which have
      distinctive size effects along with facile modification strategies and are
      capable of mediating effective RNAi with targeting potential, are attracting
      extensive interest. OBJECTIVE: This review presents an overview of the mechanisms
      of RNAi molecules in gene therapy and the different nanoparticles used to deliver
      RNAi molecules; briefly describes the current uses of RNAi in cancer therapy
      along with the nano-based delivery of RNA molecules in previous studies; and
      highlights some other carriers that have been applied in clinical settings.
      Finally, we discuss the nano-based delivery of RNAi therapeutics in preclinical
      development, including the current status and limitations of anti-cancer
      treatment. CONCLUSION: With the growing number of RNAi therapeutics entering the
      clinical phase, various nanocarriers are expected to play important roles in the
      delivery of RNAi molecules for cancer therapeutics.

PMID- 28754121
TI  - Coiled-coil domain containing 109B is a HIF1alpha-regulated gene critical for
      progression of human gliomas.
AB  - BACKGROUND: The coiled-coil domain is a structural motif found in proteins that
      participate in a variety of biological processes. Aberrant expression of such
      proteins has been shown to be associated with the malignant behavior of human
      cancers. In this study, we investigated the role of a specific family member,
      coiled-coil domain containing 109B (CCDC109B), in human gliomas. METHODS AND
      RESULTS: We confirmed that CCDC109B was highly expressed in high grade gliomas
      (HGG; WHO III-IV) using immunofluorescence, western blot analysis,
      immunohistochemistry (IHC) and open databases. Through Cox regression analysis of
      The Cancer Genome Atlas (TCGA) database, we found that the expression levels of
      CCDC109B were inversely correlated with patient overall survival and it could
      serve as a prognostic marker. Then, a serious of cell functional assays were
      performed in human glioma cell lines, U87MG and U251, which indicated that
      silencing of CCDC109B attenuated glioma proliferation and migration/invasion both
      in vitro and in vivo. Notably, IHC staining in primary glioma samples
      interestingly revealed localization of elevated CCDC109B expression in necrotic
      areas which are typically hypoxic. Moreover, small interfering RNA (siRNA) and
      specific inhibiters of HIF1alpha led to decreased expression of CCDC109B in vitro
      and in vivo. Transwell assay further showed that CCDC109B is a critical factor in
      mediating HIF1alpha-induced glioma cell migration and invasion. CONCLUSION: Our
      study elucidated a role for CCDC109B as an oncogene and a prognostic marker in
      human gliomas. CCDC109B may provide a novel therapeutic target for the treatment
      of human glioma.

PMID- 28754122
TI  - Snoopy's hybrid simulator: a tool to construct and simulate hybrid biological
      models.
AB  - BACKGROUND: Hybrid simulation of (computational) biochemical reaction networks,
      which combines stochastic and deterministic dynamics, is an important direction
      to tackle future challenges due to complex and multi-scale models. Inherently
      hybrid computational models of biochemical networks entail two time scales: fast
      and slow. Therefore, it is intricate to efficiently and accurately analyse them
      using only either deterministic or stochastic simulation. However, there are only
      a few software tools that support such an approach. These tools are often limited
      with respect to the number as well as the functionalities of the provided hybrid
      simulation algorithms. RESULTS: We present Snoopy's hybrid simulator, an
      efficient hybrid simulation software which builds on Snoopy, a tool to construct
      and simulate Petri nets. Snoopy's hybrid simulator provides a wide range of state
      of-the-art hybrid simulation algorithms. Using this tool, a computational model
      of biochemical networks can be constructed using a (coloured) hybrid Petri net's
      graphical notations, or imported from other compatible formats (e.g. SBML), and
      afterwards executed via dynamic or static hybrid simulation. CONCLUSION: Snoopy's
      hybrid simulator is a platform-independent tool providing an accurate and
      efficient simulation of hybrid (biological) models. It can be downloaded free of
      charge as part of Snoopy from http://www-dssz.informatik.tu
      cottbus.de/DSSZ/Software/Snoopy .

PMID- 28754123
TI  - Post-mortem molecular profiling of three psychiatric disorders.
AB  - BACKGROUND: Psychiatric disorders are multigenic diseases with complex etiology
      that contribute significantly to human morbidity and mortality. Although
      clinically distinct, several disorders share many symptoms, suggesting common
      underlying molecular changes exist that may implicate important regulators of
      pathogenesis and provide new therapeutic targets. METHODS: We performed RNA
      sequencing on tissue from the anterior cingulate cortex, dorsolateral prefrontal
      cortex, and nucleus accumbens from three groups of 24 patients each diagnosed
      with schizophrenia, bipolar disorder, or major depressive disorder, and from 24
      control subjects. We identified differentially expressed genes and validated the
      results in an independent cohort. Anterior cingulate cortex samples were also
      subjected to metabolomic analysis. ChIP-seq data were used to characterize
      binding of the transcription factor EGR1. RESULTS: We compared molecular
      signatures across the three brain regions and disorders in the transcriptomes of
      post-mortem human brain samples. The most significant disease-related differences
      were in the anterior cingulate cortex of schizophrenia samples compared to
      controls. Transcriptional changes were assessed in an independent cohort,
      revealing the transcription factor EGR1 as significantly down-regulated in both
      cohorts and as a potential regulator of broader transcription changes observed in
      schizophrenia patients. Additionally, broad down-regulation of genes specific to
      neurons and concordant up-regulation of genes specific to astrocytes was observed
      in schizophrenia and bipolar disorder patients relative to controls. Metabolomic
      profiling identified disruption of GABA levels in schizophrenia patients.
      CONCLUSIONS: We provide a comprehensive post-mortem transcriptome profile of
      three psychiatric disorders across three brain regions. We highlight a high
      confidence set of independently validated genes differentially expressed between
      schizophrenia and control patients in the anterior cingulate cortex and integrate
      transcriptional changes with untargeted metabolite profiling.

PMID- 28754124
TI  - Manatee invariants reveal functional pathways in signaling networks.
AB  - BACKGROUND: Signal transduction pathways are important cellular processes to
      maintain the cell's integrity. Their imbalance can cause severe pathologies. As
      signal transduction pathways feature complex regulations, they form intertwined
      networks. Mathematical models aim to capture their regulatory logic and allow an
      unbiased analysis of robustness and vulnerability of the signaling network.
      Pathway detection is yet a challenge for the analysis of signaling networks in
      the field of systems biology. A rigorous mathematical formalism is lacking to
      identify all possible signal flows in a network model. RESULTS: In this paper, we
      introduce the concept of Manatee invariants for the analysis of signal
      transduction networks. We present an algorithm for the characterization of the
      combinatorial diversity of signal flows, e.g., from signal reception to cellular
      response. We demonstrate the concept for a small model of the TNFR1-mediated NF-
      kappaB signaling pathway. Manatee invariants reveal all possible signal flows in
      the network. Further, we show the application of Manatee invariants for in silico
      knockout experiments. Here, we illustrate the biological relevance of the
      concept. CONCLUSIONS: The proposed mathematical framework reveals the entire
      variety of signal flows in models of signaling systems, including cyclic
      regulations. Thereby, Manatee invariants allow for the analysis of robustness and
      vulnerability of signaling networks. The application to further analyses such as
      for in silico knockout was shown. The new framework of Manatee invariants
      contributes to an advanced examination of signaling systems.

PMID- 28754125
TI  - Syk inhibitors in clinical development for hematological malignancies.
AB  - Spleen tyrosine kinase (Syk) is a cytosolic non-receptor protein tyrosine kinase
      (PTK) and is mainly expressed in hematopoietic cells. Syk was recognized as a
      critical element in the B-cell receptor signaling pathway. Syk is also a key
      component in signal transduction from other immune receptors like Fc receptors
      and adhesion receptors. Several oral Syk inhibitors including fostamatinib
      (R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659 are being
      assessed in clinical trials. The second generation compound, entospletinib,
      showed promising results in clinical trials against B-cell malignancies, mainly
      chronic lymphoid leukemia. Syk inhibitors are being evaluated in combination
      regimens in multiple malignancies.

PMID- 28754126
TI  - Modulation of chromatin structure by the FACT histone chaperone complex regulates
      HIV-1 integration.
AB  - BACKGROUND: Insertion of retroviral genome DNA occurs in the chromatin of the
      host cell. This step is modulated by chromatin structure as nucleosomes
      compaction was shown to prevent HIV-1 integration and chromatin remodeling has
      been reported to affect integration efficiency. LEDGF/p75-mediated targeting of
      the integration complex toward RNA polymerase II (polII) transcribed regions
      ensures optimal access to dynamic regions that are suitable for integration.
      Consequently, we have investigated the involvement of polII-associated factors in
      the regulation of HIV-1 integration. RESULTS: Using a pull down approach coupled
      with mass spectrometry, we have selected the FACT (FAcilitates Chromatin
      Transcription) complex as a new potential cofactor of HIV-1 integration. FACT is
      a histone chaperone complex associated with the polII transcription machinery and
      recently shown to bind LEDGF/p75. We report here that a tripartite complex can be
      formed between HIV-1 integrase, LEDGF/p75 and FACT in vitro and in cells.
      Biochemical analyzes show that FACT-dependent nucleosome disassembly promotes HIV
      1 integration into chromatinized templates, and generates highly favored
      nucleosomal structures in vitro. This effect was found to be amplified by
      LEDGF/p75. Promotion of this FACT-mediated chromatin remodeling in cells both
      increases chromatin accessibility and stimulates HIV-1 infectivity and
      integration. CONCLUSIONS: Altogether, our data indicate that FACT regulates HIV-1
      integration by inducing local nucleosomes dissociation that modulates the
      functional association between the incoming intasome and the targeted nucleosome.

PMID- 28754127
TI  - Predictive biomarkers of resistance to hypofractionated radiotherapy in high
      grade glioma.
AB  - BACKGROUND: Radiotherapy plays a major role in the management of high grade
      glioma. However, the radioresistance of glioma cells limits its efficiency and
      drives recurrence inside the irradiated tumor volume leading to poor outcome for
      patients. Stereotactic hypofractionated radiotherapy is one option for recurrent
      high grade gliomas. Optimization of hypofractionated radiotherapy with new
      radiosensitizing agents requires the identification of robust druggable targets
      involved in radioresistance. METHODS: We generated 11 xenografted glioma models:
      6 were derived from cell lines (1 WHO grade III and 5 grade IV) and 5 were
      patient derived xenografts (2 WHO grade III and 3 grade IV). Xenografts were
      treated by hypofractionated radiotherapy (6x5Gy). We searched for 89 biomarkers
      of radioresistance (39 total proteins, 26 phosphoproteins and 24 ratios of
      phosphoproteins on total proteins) using Reverse Phase Protein Array. RESULTS:
      Both type of xenografted models showed equivalent spectrum of sensitivity and
      profile of response to hypofractionated radiotherapy. We report that Phospho
      EGFR/EGFR, Phospho-Chk1/Chk1 and VCP were associated to resistance to
      hypofractionated radiotherapy. CONCLUSIONS: Several compounds targeting EGFR or
      CHK1 are already in clinical use and combining them with stereotactic
      hypofractionated radiotherapy for recurrent high grade gliomas might be of
      particular interest.

PMID- 28754128
TI  - Does air pollution play a role in infertility?: a systematic review.
AB  - BACKGROUND: Air pollution is involved in many pathologies. These pollutants act
      through several mechanisms that can affect numerous physiological functions,
      including reproduction: as endocrine disruptors or reactive oxygen species
      inducers, and through the formation of DNA adducts and/or epigenetic
      modifications. We conducted a systematic review of the published literature on
      the impact of air pollution on reproductive function. Eligible studies were
      selected from an electronic literature search from the PUBMED database from
      January 2000 to February 2016 and associated references in published studies.
      Search terms included (1) ovary or follicle or oocyte or testis or testicular or
      sperm or spermatozoa or fertility or infertility and (2) air quality or O3 or NO2
      or PM2.5 or diesel or SO2 or traffic or PM10 or air pollution or air pollutants.
      The literature search was conducted in accordance with the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We have
      included the human and animal studies corresponding to the search terms and
      published in English. We have excluded articles whose results did not concern
      fertility or gamete function and those focused on cancer or allergy. We have also
      excluded genetic, auto-immune or iatrogenic causes of reduced reproduction
      function from our analysis. Finally, we have excluded animal data that does not
      concern mammals and studies based on results from in vitro culture. Data have
      been grouped according to the studied pollutants in order to synthetize their
      impact on fertility and the molecular pathways involved. CONCLUSION: Both animal
      and human epidemiological studies support the idea that air pollutants cause
      defects during gametogenesis leading to a drop in reproductive capacities in
      exposed populations. Air quality has an impact on overall health as well as on
      the reproductive function, so increased awareness of environmental protection
      issues is needed among the general public and the authorities.

PMID- 28754129
TI  - 3-(2-Chloropropyl amide)-4-methoxy-N-phenylbenzamide inhibits expression of HPV
      oncogenes in human cervical cancer cell.
AB  - BACKGROUND: Human papillomaviruses (HPVs) are the primary causative agents for
      cervical cancer, and HPV oncoproteins E6 and E7 are known to be the main reason
      for the onset and maintenance of the malignancies. Therefore, inhibition of viral
      E6 and E7 oncoproteins expression represents a viable strategy to cervical cancer
      therapies. This study is to evaluate the antiviral effect of a novel N
      Phenylbenzamide derivative, 3-(2-Chloropropyl amide)-4-methoxy-N-phenylbenzamide
      (L17), against HPV16 in vitro and identify its associated mechanism of action in
      cervical cancer cells. METHODS: The cytotoxic effect of L17 was assessed by MTT
      assay. The mRNA and protein levels of E6 and E7 oncogenes were analyzed by
      quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot,
      respectively. p53 and Rb protein levels were also detected by Western blot. The
      effect of L17 on cell cycle was analyzed by flow cytometry. RESULTS: The
      cytotoxic effect of L17 was greater in cervical carcinoma cells than in normal
      cells. L17 significantly reduced the expression of HPV16 E6 and E7 mRNA and
      protein, at least partly by enhancing degradation of HPV16 E6 and E7 mRNA.
      Moreover, reduced expression of E6 and E7 induced by L17 resulted in the up
      regulation of p53 and Rb expression, which subsequently induced CaSki cells
      arrest at G0/G1 phase. CONCLUSIONS: L17 has antiviral activity through
      suppressing E6 and E7 oncogene expression and could inhibit CaSki cell
      proliferating by inducing cells arrest at G0/G1 phase at nontoxic concentration,
      implying that L17 might be exploited as a candidate agent for HPV-associated
      cervical cancer prevention and treatment.

PMID- 28754130
TI  - Teasing apart "the tangled web" of influence of policy dialogues: lessons from a
      case study of dialogues about healthcare reform options for Canada.
AB  - BACKGROUND: The knowledge exchange literature suggests that policy dialogues are
      intended to enhance short-, medium- and long-term capacities of individuals,
      organizations and health systems to use evidence to inform policy-making. Key
      features of effective dialogues have been suggested, but the linkages between
      these features and the realization of improved capacities for evidence-informed
      policy-making among dialogue attendees and the subsequent influence on policy
      making activities are not well understood. METHODS: We conducted a qualitative
      case study of a series of four policy dialogues that were convened in Canada
      among national, provincial and regional stakeholders on topics pertaining to
      healthcare financing and funding in 2011. Data sources included videos of
      participant perspectives captured during or immediately following each event and
      follow-up key informant interviews among dialogue participants held 4 years later
      in 2015. Three conceptual frameworks pertaining to (i) policy dialogues and
      capacities for evidence use, (ii) factors shaping policy-making across the policy
      cycle and (iii) factors shaping implementation of evidence guided the thematic
      analysis. We then synthesized the findings across the three frameworks. RESULTS:
      The results suggest the potential benefits of policy dialogues described in the
      literature were developed among the participants at these dialogues. Informants
      elaborated on how dialogue features influenced their capacities to use evidence,
      the ideas, interests and institutions during the agenda-setting and policy
      formulation stages of policy-making and how implementation was affected by
      characteristics of policy options, individuals, organizations, the external
      environment and processes. CONCLUSIONS: We present a conceptual framework that
      furthers our understanding of the potential influence of policy dialogues on the
      content and mechanisms of policy development and illustrate pathways of influence
      on various stages of the policy cycle from agenda setting through formulation and
      implementation. The framework highlights important factors for consideration in
      designing and evaluating policy dialogues and in supporting post-dialogue
      knowledge exchange efforts.

PMID- 28754131
TI  - A translocator protein 18 kDa agonist protects against cerebral
      ischemia/reperfusion injury.
AB  - BACKGROUND: Cerebral ischemia is a leading cause of death and disability with
      limited treatment options. Although inflammatory and immune responses participate
      in ischemic brain injury, the molecular regulators of neuroinflammation after
      ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly
      localized to the mitochondrial outer membrane is predominantly expressed in glia
      within the central nervous system during inflammatory conditions. This study
      investigated the effect of a TSPO agonist, etifoxine, on neuroinflammation and
      brain injury after ischemia/reperfusion. METHODS: We used a mouse model of middle
      cerebral artery occlusion (MCAO) to examine the therapeutic potential and
      mechanisms of neuroprotection by etifoxine. RESULTS: TSPO was upregulated in
      Iba1+ or CD11b+CD45int cells from mice subjected to MCAO and reperfusion.
      Etifoxine significantly attenuated neurodeficits and infarct volume after MCAO
      and reperfusion. The attenuation was pronounced in mice subjected to 30, 60, or
      90 min MCAO. Etifoxine reduced production of pro-inflammatory factors in the
      ischemic brain. In addition, etifoxine treatment led to decreased expression of
      interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and inducible
      nitric oxide synthase by microglia. Notably, the benefit of etifoxine against
      brain infarction was ablated in mice depleted of microglia using a colony
      stimulating factor 1 receptor inhibitor. CONCLUSIONS: These findings indicate
      that the TSPO agonist, etifoxine, reduces neuroinflammation and brain injury
      after ischemia/reperfusion. The therapeutic potential of targeting TSPO requires
      further investigations in ischemic stroke.

PMID- 28754132
TI  - Interactions between glycopyrronium and indacaterol on cholinergic
      neurotransmission and contractile response in bovine trachealis.
AB  - BACKGROUND: Muscarinic-receptor antagonists and beta-adrenoceptor agonists are
      used, alone or in combination, as first-line treatment for chronic obstructive
      pulmonary disease. Both drugs decrease airway smooth muscle tone by post
      junctional mechanisms but they may have opposing effects on pre-junctional
      acetylcholine (ACh)-release. METHODS: We studied the effects of the muscarinic
      receptor antagonist glycopyrronium (GLY), the beta-adrenoceptor agonist
      indacaterol (IND) and their combination on electrically-induced ACh-release and
      contractile response in isolated bovine trachealis. Data were analyzed by paired
      t-test and analysis of variance for repeated or independent measures with Newmann
      Keuls post-hoc test when appropriate. RESULTS: GLY 10-8 M decreased contractile
      response by 19 +/- 6% (p = 0.010) without altering ACh-release. GLY 10-7 M and 10
      6 M almost abolished contractile responses even if the ACh-release was increased
      by 27 +/- 19% (p < 0.001) and 20 +/- 8% (p = 0.004), respectively. IND 10-7 M had
      no significant effects on contractile response and ACh-release, whereas IND 10-6
      M reduced contractile response by 24 +/- 12% (p = 0.002) without altering ACh
      release. IND 10-5 M decreased contractile response by 51 +/- 17% (p < 0.001) and
      ACh-release by 22 +/- 11% (p = 0.004). Co-incubation with GLY 10-8 M and IND 10-7
      M did not alter ACh-release but inhibited contractile response by 41 +/- 8% (p <
      0.001). The latter effect was greater than with GLY 10-8 M, or IND 10-7 M, or IND
      10-6 M given separately (p < 0.001 for all). The increment of ACh-release caused
      by GLY was attenuated by IND 10-5 M, though this did not affect contractile
      response. CONCLUSIONS: At equimolar concentration, GLY alone attenuates airway
      smooth muscle contraction more than IND, despite an increased ACh-release.
      Combination of GLY with IND at submaximal concentrations has more than additive
      effect suggesting a synergistic post-junctional effect. Adding GLY to IND
      provides a greater inhibitory effect on airway smooth muscle contraction than
      increasing IND concentration.

PMID- 28754133
TI  - Determinants of eating patterns and nutrient intake among adolescent athletes: a
      systematic review.
AB  - BACKGROUND: This review aims to update the influences of sport modalities, sport
      performance, and non-exercise-related determinant, on eating patterns and
      nutrient intake outcomes among adolescent competitive athletes. METHODS: The
      PubMed and Scopus databases were searched for the last 20 years. Observational
      and intervention studies of all languages on eating patterns and nutrient intake
      in adolescent (10- to 19-year-old) competitive athletes were included. Study
      quality and risk of bias were assessed using a Downs and Black instrument.
      Moreover, the Grading of Recommendations, Assessment, Development and Evaluations
      (GRADE) evidence system was used to assess the strength of the body of evidence.
      RESULTS: Regarding outcomes of 21 included articles, 95.2% of studies focused on
      nutrient analysis, whereas few of the included articles reported eating patterns.
      As determinants, most studies analyzed the influences of sport-related (n = 10)
      and demographic factors (n = 8), among which only sport modalities were
      significantly associated with nutrient intake. Age and sex were not significantly
      associated with nutrient intake. All studies were observational, and most were
      cross-sectional (n = 17) and conducted in developed countries such as the United
      States and European nations. Most studies evaluated boys, and the sport that
      received the most attention was soccer. CONCLUSIONS: Athletes do not adjust their
      nutrient intake or food choice to the demands of the training load or different
      training sessions, while sport modalities significantly influenced nutrient
      intake. Moreover, results concerning demographic determinants were inconsistent
      and thus remain inconclusive. TRIAL REGISTRATION: Prospero CRD42016043310 .

PMID- 28754135
TI  - Retrofitting the BAC cloning vector pBeloBAC11 by the insertion of a mutant loxP
      site.
AB  - OBJECTIVE: Human genomic libraries constructed in bacterial artificial chromosome
      vectors were utilized to make physical maps of all 23-chromosome pairs and as the
      templates for DNA sequencing to aid in the completion of the Human Genome
      Project. The goal of this study was to modify the BAC vector pBeloBAC11 so that
      genomic inserts contained in this vector could be subjected to bidirectional
      transposon-mediated nested deletions from the wild-type and mutant loxP sites
      present. RESULTS: An oligonucleotide containing a mutant loxP 2272 site and a
      XhoI restriction enzyme sequence was designed and inserted at the SfiI
      restriction site located approximately 200 basepairs upstream of the lacZ gene in
      pBeloBAC11. Clones containing the desired insert were identified by XhoI
      restriction digests since an additional band was generated. This transposon
      mediated deletion technology allows researchers to identify the boundaries of cis
      acting elements and genes.

PMID- 28754134
TI  - Occurrence of a novel mastrevirus in sugarcane germplasm collections in Florida,
      Guadeloupe and Reunion.
AB  - BACKGROUND: In Africa and Asia, sugarcane is the host of at least seven different
      virus species in the genus Mastrevirus of the family Geminiviridae. However, with
      the exception of Sugarcane white streak virus in Barbados, no other sugarcane
      infecting mastrevirus has been reported in the New World. Conservation and
      exchange of sugarcane germplasm using stalk cuttings facilitates the spread of
      sugarcane-infecting viruses. METHODS: A virion-associated nucleic acids (VANA)
      based metagenomics approach was used to detect mastrevirus sequences in 717
      sugarcane samples from Florida (USA), Guadeloupe (French West Indies), and
      Reunion (Mascarene Islands). Contig assembly was performed using CAP3 and
      sequence searches using BLASTn and BLASTx. Mastrevirus full genomes were enriched
      from total DNA by rolling circle amplification, cloned and sequenced. Nucleotide
      and amino acid sequence identities were determined using SDT v1.2. Phylogenetic
      analyses were conducted using MEGA6 and PHYML3. RESULTS: We identified a new
      sugarcane-infecting mastrevirus in six plants sampled from germplasm collections
      in Florida and Guadeloupe. Full genome sequences were determined and analyzed for
      three virus isolates from Florida, and three from Guadeloupe. These six genomes
      share >88% genome-wide pairwise identity with one another and between 89 and 97%
      identity with a recently identified mastrevirus (KR150789) from a sugarcane plant
      sampled in China. Sequences similar to these were also identified in sugarcane
      plants in Reunion. CONCLUSIONS: As these virus isolates share <64% genome-wide
      identity with all other known mastreviruses, we propose classifying them within a
      new mastrevirus species named Sugarcane striate virus. This is the first report
      of sugarcane striate virus (SCStV) in the Western Hemisphere, a virus that most
      likely originated in Asia. The distribution, vector, and impact of SCStV on
      sugarcane production remains to be determined.

PMID- 28754136
TI  - Women's satisfaction with intrapartum care in St Paul's Hospital Millennium
      Medical College Addis Ababa Ethiopia: a cross sectional study.
AB  - BACKGROUND: Satisfaction during intrapartum care is the most influential
      attribute on maternal health service return behaviors and utilization. Measuring
      satisfaction of women with intrapartum care helps to address the problems and
      improves the quality of delivery services. The aim of this study is to assess
      women's level of satisfaction during intrapartum care. METHOD: A hospital based,
      analytic, cross sectional study was conducted at St. Paul's Hospital Millennium
      Medical College (SPHMMC), Addis Ababa Ethiopia, from May to June 2015. Data
      collectors administered a structured and pretested questionnaire to collect data
      and then analyzed it using SPSS version 20.0 software. Binary logistic regression
      was used to identify factors associated with women's intrapartum care
      satisfaction. RESULT: A total of 394 women of mean age 25.98 years with a
      standard deviation of +/-4.72were included in the study. Only 19% of the women
      were satisfied with the intrapartum care they received. The variables which were
      significantly associated with satisfaction of intrapartum care were; opportunity
      to talk Adjusted Odds Ratio (AOR) (95% CI) 2.44 (1.12, 5.29); Pain Management AOR
      (95% CI) 3.37 (1.83, 6.21); Short Length of Time Taken for Admission After Seen
      by Health Professionals AOR (95% CI)0 .97 (0.93, 0.99), and Short Length of Stay
      in the Hospital AOR (95% CI) 0.91 (0.87, 0.96). CONCLUSIONS: The women's overall
      satisfaction with intrapartum care was low. Multiple factors influence their
      satisfaction. Health professionals, policy makers and health administrators
      should give emphasis to factors that contribute to low satisfaction of women with
      intrapartum care. They should also strengthen their efforts to deliver quality
      and easily accessible maternal health service to improve women's overall
      satisfaction with the maternal health service.

PMID- 28754137
TI  - Tuberculous monoarthritis of the wrist in a patient with systemic lupus
      erythematosus: a case report.
AB  - BACKGROUND: Unusual forms of tuberculosis are common among immune-suppressed
      patients, leading to challenges in diagnosis and management. We present a Sri
      Lankan patient with systemic lupus erythematosis, investigated for chronic wrist
      pain with low inflammatory markers and without systemic symptoms, who was
      subsequently diagnosed to have tuberculosis of the joint. CASE PRESENTATION: A 31
      year-old woman with systemic lupus erythematosis in remission was evaluated for
      chronic left wrist pain without significant examination findings on presentation.
      She did not have any constitutional symptoms. Basic investigations did not reveal
      any significant abnormalities. She was treated with increasing immunosuppression
      as for lupus related arthritis. Subsequently she developed a wrist effusion with
      high inflammatory markers, and was treated as septic arthritis. Synovial biopsy
      features suggested tuberculosis. The patient's symptoms improved with surgical
      intervention and anti-tuberculosis treatment. CONCLUSION: Tuberculosis should be
      considered in patients with systemic arthritis with unusual symptoms. Delayed
      diagnosis along with continuing immunosuppression can lead to extensive tissue
      damage. Clinically detectable effusions should be analyzed along with synovial
      biopsy in order to exclude concurrent infections. Radiography of the joint has
      poor sensitivity to detect early joint damage, but changes may be evident early
      on magnetic resonance imaging, sothis should be considered in patients with
      unusual features.

PMID- 28754138
TI  - Serological and PCR investigation of Yersinia pestis in potential reservoir hosts
      from a plague outbreak focus in Zambia.
AB  - BACKGROUND: Plague is a bacterial zoonotic disease, caused by Yersinia pestis.
      Rodents are the natural hosts with fleas as the vehicle of disease transmission.
      Domestic and wild dogs and cats have also been identified as possible disease
      hosts. In Zambia, plague outbreaks have been reported in the Southern and Eastern
      regions in the last 20 years. Based on these observations, Y. pestis could
      possibly be endemically present in the area. METHODS: To substantiate such
      possibility, sera samples were collected from rodents, shrews, dogs and cats for
      detection of antibodies against Fraction 1 gene (Fra1) of Y. pestis while organs
      from rodents and shrews, and fleas from both dogs and rodents were collected to
      investigate plasminogen activator gene (pla gene) of Y. pestis using ELISA and
      PCR respectively. RESULTS: A total of 369 blood samples were collected from
      domestic carnivores, shrews and domestic and peri-domestic rodents while 199
      organs were collected from the rodents and shrews. Blood samples were tested for
      antibodies against Fra1 antigen using ELISA and 3% (5/165) (95% CI 0.99-6.93%)
      dogs were positive while all cats were negative. Of 199 sera from rodents and
      shrews, 12.6% (95% CI 8.30-17.98%) were positive for antibodies against Fra1
      using anti-rat IgG secondary antibody while using anti-mouse IgG secondary
      antibody, 17.6% (95% CI 12.57-23.60%) were positive. PCR was run on the organs
      and 2.5% (95% CI 0.82-5.77%) were positive for plasminogen activator gene of Y.
      pestis and the amplicons were sequenced and showed 99% identity with Y. pestis
      reference sequences. All 82 fleas collected from animals subjected to PCR, were
      negative for pla gene. The specific rat-flea and dog-flea indices were 0.19 and
      0.27 respectively, which were lower than the level required to enhance chances of
      the disease outbreak. CONCLUSIONS: We concluded that plague was still endemic in
      the area and the disease may infect human beings if contact is enhanced between
      reservoir hosts and flea vectors. The lower specific rodent-flea Indices and
      absence of Y. pestis in the potential vectors were considered to be partly
      responsible for the current absence of plague outbreaks despite its presence in
      the sylvatic cycle.

PMID- 28754139
TI  - Evidence of altered haemostasis in an ovine model of venovenous extracorporeal
      membrane oxygenation support.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving modality
      used in the management of cardiopulmonary failure that is refractory to
      conventional medical and surgical therapies. The major problems clinicians face
      are bleeding and clotting, which can occur simultaneously. To discern the impact
      of pulmonary injury and ECMO on the host's haemostatic response, we developed an
      ovine model of smoke-induced acute lung injury (S-ALI) and ECMO. The aims of this
      study were to determine if the ECMO circuit itself altered haemostasis and if
      this was augmented in a host with pulmonary injury. METHODS: Twenty-seven South
      African meat merino/Border Leicester Cross ewes underwent instrumentation.
      Animals received either sham injury (n = 12) or S-ALI (n = 15). Control animal
      groups consisted of healthy controls (ventilation only for 24 h) (n = 4), ECMO
      controls (ECMO only for 24 h) (n = 8) and S-ALI controls (S-ALI but no ECMO for
      24 h) (n = 7). The test group comprised S-ALI sheep placed on ECMO (S-ALI + ECMO
      for 24 h) (n = 8). Serial blood samples were taken for rotational
      thromboelastometry, platelet aggregometry and routine coagulation laboratory
      tests. Animals were continuously monitored for haemodynamic, fluid and
      electrolyte balances and temperature. Pressure-controlled intermittent mandatory
      ventilation was used, and mean arterial pressure was augmented by protocolised
      use of pressors, inotropes and balanced fluid resuscitation to maintain mean
      arterial pressure >65 mmHg. RESULTS: Rotational thromboelastometry, platelet
      aggregometry and routine coagulation laboratory tests demonstrated that S-ALI and
      ECMO independently induced changes to platelet function, delayed clot formation
      and reduced clot firmness. This effect was augmented with the combination of S
      ALI and ECMO, with evidence of increased collagen-induced platelet aggregation as
      well as changes in factor VIII (FVIII), factor XII and fibrinogen levels.
      CONCLUSIONS: The introduction of an ECMO circuit itself increases collagen
      induced platelet aggregation, decreases FVIII and von Willebrand factor, and
      induces a transient decrease in fibrinogen levels and function in the first 24 h.
      These changes to haemostasis are amplified when a host with a pre-existing
      pulmonary injury is placed on ECMO. Because patients are often on ECMO for
      extended periods, longer-duration studies are required to characterise ECMO
      induced haemostatic changes over the long term. The utility of point-of-care
      tests for guiding haemostatic management during ECMO also warrants further
      exploration.

PMID- 28754140
TI  - Assessing citation networks for dissemination and implementation research
      frameworks.
AB  - BACKGROUND: A recent review of frameworks used in dissemination and
      implementation (D&I) science described 61 judged to be related either to
      dissemination, implementation, or both. The current use of these frameworks and
      their contributions to D&I science more broadly has yet to be reviewed. For these
      reasons, our objective was to determine the role of these frameworks in the
      development of D&I science. METHODS: We used the Web of ScienceTM Core Collection
      and Google ScholarTM to conduct a citation network analysis for the key
      frameworks described in a recent systematic review of D&I frameworks (Am J Prev
      Med 43(3):337-350, 2012). From January to August 2016, we collected framework
      data including title, reference, publication year, and citations per year and
      conducted descriptive and main path network analyses to identify those most
      important in holding the current citation network for D&I frameworks together.
      RESULTS: The source article contained 119 cited references, with 50 published
      articles and 11 documents identified as a primary framework reference. The
      average citations per year for the 61 frameworks reviewed ranged from 0.7 to
      103.3 among articles published from 1985 to 2012. Citation rates from all
      frameworks are reported with citation network analyses for the framework review
      article and ten highly cited framework seed articles. The main path for the D&I
      framework citation network is presented. CONCLUSIONS: We examined citation rates
      and the main paths through the citation network to delineate the current
      landscape of D&I framework research, and opportunities for advancing framework
      development and use. Dissemination and implementation researchers and
      practitioners may consider frequency of framework citation and our network
      findings when planning implementation efforts to build upon this foundation and
      promote systematic advances in D&I science.

PMID- 28754141
TI  - Short stature: an ordinary sign for an unordinary diagnosis.
AB  - BACKGROUND: Short stature (SS) is a relatively early sign of poor health. Only in
      5% of cases we can explain it through the presence of endocrinological
      pathologies. Therefore, if SS is present since the first months of life, it is
      necessary to investigate all systemic disorders with secondary effects on growth.
      CASE PRESENTATION: We report the case of a 16-months-old male infant with severe
      SS apparently not associated with other clinical signs or symptoms. The patient
      arrived to our attention after he was hospitalized for an Echovirus enteritis,
      associated to moderate neutropenia (800/mm3) and hypertransaminasemia (AST 116
      U/L, ALT 88 U/L) at the age of 13 months. SS was detected in that occasion. Since
      SS persisted even after the complete resolution of enteritis symptoms, he was
      taken care by our unit. CONCLUSIONS: SS appeared in the first months of life and
      associated with moderate neutropenia and hypertransaminasemia led us to the
      diagnosis of Shwachmann-Diamond syndrome. We recommend paying further attention
      to this condition during the differential diagnosis of children with severe SS.

PMID- 28754142
TI  - Development and validation of a real-time PCR assay for the detection of clinical
      acanthamoebae.
AB  - BACKGROUND: Suboptimal agreement between molecular assays for the detection of
      Acanthamoeba spp. in clinical specimens has been demonstrated, and poor assay
      sensitivity directly imperils the vision of those affected by amoebic keratitis
      (AK) through delayed diagnosis. We sought to develop and validate a single Taqman
      real time PCR assay targeting the Acanthamoeba 18S rRNA gene that could be used
      to enhance sensitivity and specificity when paired with reference assays.
      METHODS: Biobanked DNA from surplus delinked AK clinical specimens and 10 ATCC
      strains of Acanthamoeba was extracted. Sequence alignment of 66 18S rRNA regions
      from 12 species of Acanthamoeba known to cause keratitis informed design of a new
      TaqMan primer set. Performance of the new assay was compared to the 2 assays used
      currently in our laboratory. RESULTS: Among 24 Acanthamoeba-positive and 83
      negative specimens by the CDC reference standard, performance characteristics of
      the newly designed primer set were as follows: sensitivity 100%, specificity 94%,
      PPV 82.8%, and NPV 100%. Compared to culture, sensitivity of the new primer set
      was 100%, and specificity 96%. No cross-reactivity of the primer set to non
      acanthamoebae, including Balamuthia and Naegleria, was found. CONCLUSIONS: We
      have validated a real time PCR assay for the diagnosis of AK, and in doing so,
      have overcome important barriers to rapid and sensitive detection of
      acanthamoebae, including limited sensitivity and specificity of commonly used
      assays.

PMID- 28754143
TI  - Predictors of positive esophagogastroduodenoscopy outcomes in children and
      adolescents: a single center experience.
AB  - BACKGROUND: Esophagogastroduodenoscopy (EGD) has become a key element in the
      diagnosis and therapy of many gastrointestinal diseases affecting children. The
      aim of this study was to evaluate predictors of positive outcomes in children
      undergoing their first diagnostic EGD with biopsies at a single center. RESULTS:
      This retrospective study was based on findings from existing EGD and
      histopathological reports. All procedures were performed between July 2006 and
      July 2013. Details of each patient's clinical presentation and EGD were
      abstracted from medical records to determine the predictors of positive EGD
      outcomes. A total of 1133 records of patients between the ages of 0 and 18 years
      old were evaluated. Of these patients, 51.5% (n = 573) were female and 24.5% (n =
      278) were younger than 4 years old. The mean age at the time of EGD was 9.6 +/-
      5.7 years (mean +/- standard deviation). The most common indications for the
      procedure were abdominal pain (54.9%) and emesis (31.9%). The overall prevalence
      of any endoscopic abnormality was 54.5% and the overall prevalence of any
      histological abnormality was 59.1%. A multivariate logistic regression found that
      patients 12 years or older (odds ratio, OR = 1.46; 95% confidence interval, CI
      1.31-1.63), African-American race (OR = 2.20; 95% CI 1.45-3.34), dysphagia (OR =
      1.96; 95% CI 1.28-3.00) and positive celiac antibodies (OR = 2.25; 95% CI 1.52
      3.34) were all significant independent predictors of a positive EGD outcome.
      CONCLUSIONS: Several clinical variables were found to be independent predictors
      of positive EGD outcomes in children and adolescents. Prospective studies using
      standardized definitions of clinical variables and endoscopy outcomes are needed
      to further understand predictors of positive EGDs.

PMID- 28754144
TI  - A novel mechanism for variable phenotypic expressivity in Mendelian diseases
      uncovered by an AU-rich element (ARE)-creating mutation.
AB  - BACKGROUND: Variable expressivity is a well-known phenomenon in which patients
      with mutations in one gene display varying degrees of clinical severity,
      potentially displaying only subsets of the clinical manifestations associated
      with the multisystem disorder linked to the gene. This remains an incompletely
      understood phenomenon with proposed mechanisms ranging from allele-specific to
      stochastic. RESULTS: We report three consanguineous families in which an isolated
      ocular phenotype is linked to a novel 3' UTR mutation in SLC4A4, a gene known to
      be mutated in a syndromic form of intellectual disability with renal and ocular
      involvement. Although SLC4A4 is normally devoid of AU-rich elements (AREs), a 3'
      UTR motif that mediates post-transcriptional control of a subset of genes, the
      mutation we describe creates a functional ARE. We observe a marked reduction in
      the transcript level of SLC4A4 in patient cells. Experimental confirmation of the
      ARE-creating mutation is shown using a post-transcriptional reporter system that
      reveals consistent reduction in the mRNA-half life and reporter activity.
      Moreover, the neo-ARE binds and responds to the zinc finger protein ZFP36/TTP, an
      ARE-mRNA decay-promoting protein. CONCLUSIONS: This novel mutational mechanism
      for a Mendelian disease expands the potential mechanisms that underlie variable
      phenotypic expressivity in humans to also include 3' UTR mutations with tissue
      specific pathology.

PMID- 28754145
TI  - Changes in cardiac function and hemodynamics during robot-assisted laparoscopic
      prostatectomy with steep head-down tilt: a prospective observational study.
AB  - OBJECTIVE: Robot-assisted laparoscopic prostatectomy requires the patient to be
      placed in a steep head-down tilt. The aim of our study was to investigate changes
      in cardiac index and left ventricular end-diastolic volume in a steep had-down
      tilt. This is a prospective observational study. We investigated the influence of
      steep head-down tilt on cardiac function and hemodynamics without fluid
      restriction in 12 men of American Society of Anesthesiologists physical status I
      II undergoing robot-assisted laparoscopic prostatectomy. We measured left
      ventricular ejection fraction, left ventricular end-diastolic volume and cardiac
      index by transesophageal echocardiography, cardiac index using a FloTrac(r)
      sensor, heart rate and arterial blood pressure, before and 5 min after tilting
      the operating table. RESULTS: The following variables changed significantly after
      tilting and establishment of the pneumoperitoneum: left ventricular ejection
      fraction (before 62.5%, after 55.5%; P = 0.040), systolic blood pressure (before
      116 mmHg, after 128 mmHg; P = 0.001) and diastolic blood pressure (before 59
      mmHg, after 70 mmHg; P = 0.002). There were no significant changes in cardiac
      index or left ventricular end-diastolic volume measured by transesophageal
      echocardiography, or cardiac index by FloTrac(r) sensor. Left ventricular
      ejection fraction decreased, whereas cardiac index and left ventricular end
      diastolic volume did not change, indicating that steep head-down tilt and
      pneumoperitoneum during robot-assisted laparoscopic prostatectomy did not greatly
      influence cardiac function. This study was registered as a clinical study with
      the Japanese Official Clinical Trial Registry (Trial Registration Number JMA
      IIA00158 on 7th January, 2014).

PMID- 28754146
TI  - Population and allelic variation of A-to-I RNA editing in human transcriptomes.
AB  - BACKGROUND: A-to-I RNA editing is an important step in RNA processing in which
      specific adenosines in some RNA molecules are post-transcriptionally modified to
      inosines. RNA editing has emerged as a widespread mechanism for generating
      transcriptome diversity. However, there remain significant knowledge gaps about
      the variation and function of RNA editing. RESULTS: In order to determine the
      influence of genetic variation on A-to-I RNA editing, we integrate genomic and
      transcriptomic data from 445 human lymphoblastoid cell lines by combining an RNA
      editing QTL (edQTL) analysis with an allele-specific RNA editing (ASED) analysis.
      We identify 1054 RNA editing events associated with cis genetic polymorphisms.
      Additionally, we find that a subset of these polymorphisms is linked to genome
      wide association study signals of complex traits or diseases. Finally, compared
      to random cis polymorphisms, polymorphisms associated with RNA editing variation
      are located closer spatially to their respective editing sites and have a more
      pronounced impact on RNA secondary structure. CONCLUSIONS: Our study reveals
      widespread cis variation in RNA editing among genetically distinct individuals
      and sheds light on possible phenotypic consequences of such variation on complex
      traits and diseases.

PMID- 28754147
TI  - Design and implementation of a custom next generation sequencing panel for
      selected vitamin D associated genes.
AB  - BACKGROUND: Biologically active vitamin D has an important regulatory role within
      the genome. It binds the vitamin D receptor (VDR) in order to control the
      expression of a wide range of genes as well as interacting with the epigenome to
      modify chromatin and methylation status. Vitamin D deficiency is associated with
      several human diseases including end-stage renal disease. METHODS: This article
      describes the design and testing of a custom, targeted next generation sequencing
      (NGS) panel for selected vitamin D associated genes. Sequencing runs were used to
      determine the effectiveness of the panel for variant calling, to compare
      efficiency and data across different sequencers, and to perform representative,
      proof of principle association analyses. These analyses were underpowered for
      significance testing. Amplicons were designed in two pools (163 and 166 fragments
      respectively) and used to sequence two cohorts of renal transplant recipients on
      the Ion Personal Genome Machine (PGM)TM and Ion S5TM XL desktop sequencers.
      RESULTS: Coverage was provided for 43.8 kilobases across seven vitamin D
      associated genes (CYP24A1, CUBN, VDR, GC, NADSYN1, CYP27B1, CYP2R1) as well as 38
      prioritised SNPs. Sequencing runs provided sufficient sequencing quality, data
      output and validated the effective library preparation and panel design.
      CONCLUSIONS: This novel, custom-designed, validated panel provides a fast, cost
      effective, and specific approach for the analysis of vitamin D associated genes
      in a wide range of patient cohorts. This article does not report results from a
      controlled health-care intervention.

PMID- 28754149
TI  - Usability evaluation methods employed to assess information visualisations of
      electronically stored patient data for clinical use: a protocol for a systematic
      review.
AB  - BACKGROUND: The use of electronic records in healthcare is increasing. To avoid
      errors, it is essential that the data displays used by these systems are usable:
      efficient, effective and satisfying. A wide variety of display techniques are
      used to present clinical data, but the best methods to assess the usability of
      these techniques have not been determined. This systematic review will answer the
      question: What methods are employed to assess the usability of electronic
      visualisations of patient data for clinical use? The results of this systematic
      review will then be used to inform best assessment and design practice. METHODS:
      MEDLINE, EMBASE, CINAHL, OpenGrey, and the Cochrane Database of Systematic
      Reviews will be searched for original studies related to the usability of
      electronic information visualisations of patient data for clinical use. Reference
      lists of eligible studies and relevant reviews will be explored to identify
      further eligible studies. DISCUSSION: This systematic review will identify
      methods used to assess the usability of electronic information visualisations of
      patient data for clinical use. We will summarise the similarities and differences
      between the methods found. Our results will inform best practice when developing
      new user interfaces to display electronic patient data for clinical use. TRIAL
      REGISTRATION: PROSPERO CRD42016041604.

PMID- 28754148
TI  - Nosocomial bacterial infections and their antimicrobial susceptibility patterns
      among patients in Ugandan intensive care units: a cross sectional study.
AB  - BACKGROUND: The intensive care unit (ICU) admits critically ill patients
      requiring advanced airway, respiratory, cardiac and renal support. Despite the
      highly-specialized interventions, the mortality and morbidity is still high due
      to a number of reasons including nosocomial infections, which are the most likely
      complications in hospitalized patients with the rates being highest among ICU
      patients. METHODS: In this cross-sectional study of 111 adult patients admitted
      to 2 of the ICUs in Uganda, we set out to describe the commonest bacterial
      infections, their antimicrobial susceptibility patterns and factors associated
      with development of a nosocomial infection. RESULTS: Klebsiella pneumoniae (30%),
      Acinetobacter species (22%) and Staphylococcus aureus (14%) were the most
      frequently isolated bacteria. The prevalence of multidrug resistant bacterial
      species was 58%; 50% Escherichia coli and 33.3% Klebsiella pneumoniae were
      extended spectrum beta lactamase or AmpC beta lactamase producers and 9.1%
      Acinetobacter species were extensive drug resistant. Imipenem was the antibiotic
      with the highest susceptibility rates across most bacterial species. Institution
      of ventilator support (P 0.003) and severe traumatic brain injury (P 0.035) were
      highly associated with the development of nosocomial infections. CONCLUSION: Due
      to the high prevalence of multi drug resistant (MDR) and extensive drug resistant
      bacterial species, there is a need for development of strong policies on
      antibiotic stewardship, antimicrobial surveillance and infection control to help
      guide empirical antibiotic therapy and prevent the spread of MDR bacteria and
      antibiotic drug resistance.

PMID- 28754150
TI  - Characterizing expanded access and compassionate use programs for experimental
      drugs.
AB  - OBJECTIVE: We sought to determine the characteristics of "expanded access" and
      "compassionate use" programs registered in ClinicalTrials.gov and to determine
      the percentage of drugs provided through these programs that ultimately received
      FDA marketing approval. RESULTS: We identified 398 expanded access and
      compassionate use programs (hereafter referred to as expanded access programs)
      registered on ClinicalTrials.gov. Industry funded 61% (n = 241) of programs
      individually or collaboratively, while NIH and the US Federal Government rarely
      funded programs (3% [n = 11] and 2% [n = 6], respectively). Most programs
      provided access to drugs (71% [n = 282]), 11% to biologics (n = 43), and 10% to
      medical devices (n = 40). These programs covered 460 unique conditions, the most
      common being HIV (n = 26), leukemia (22), and multiple myeloma (n = 14). Only 2%
      of programs reported results in ClinicalTrials.gov. Most programs (82%) were open
      to enrolling adults and seniors (n = 326). These programs provided access to 210
      unique experimental drugs, of which 76% have received FDA approval.

PMID- 28754151
TI  - Identification of Anaplasma ovis appendage-associated protein (AAAP) for
      development of an indirect ELISA and its application.
AB  - BACKGROUND: Ovine anaplasmosis is a tick-borne disease that is caused by
      Anaplasma ovis in sheep and goats. The pathogen is widely distributed in tropical
      and subtropical regions of the world. At present, diagnosis of the disease mainly
      depends on microscopy or nucleic acid based molecular tests, although a few
      serological tests have been applied for the detection of A. ovis infection.
      RESULTS: Here we describe the identification of an A. ovis protein that is
      homologous to the A. marginale appendage-associated protein (AAAP). We expressed
      a recombinant fragment of this protein for the development of an indirect enzyme
      linked immunosorbent assay (ELISA) for the detection of A. ovis. Anaplasma ovis
      positive serum showed specific reactivity to recombinantly expressed AAAP
      (rAAAP), which was further confirmed by the rAAAP ELISA, which also demonstrated
      no cross-reactivity with sera from animals infected with A. bovis or other
      related pathogens in sheep and goats. Testing antibody kinetics of five
      experimentally infected sheep for 1 year demonstrated that the rAAAP ELISA is
      suitable for the detection of early and persistent infection of A. ovis
      infections. Investigation of 3138 field-collected serum samples from 54 regions
      in 23 provinces in China demonstrated that the seroprevalence varied from 9.4% to
      65.3%, which is in agreement with previous reports of A. ovis infection.
      CONCLUSIONS: An A. ovis derived antigenic protein, AAAP, was identified and the
      antigenicity of the recombinant AAAP was confirmed. Using rAAAP an indirect ELISA
      assay was established, and the assay has been proven to be an alternative
      serological diagnostic tool for investigating the prevalence of ovine
      anaplasmosis of sheep and goats.

PMID- 28754152
TI  - Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated
      with coma duration and long-term neurocognitive impairment in Ugandan children
      with cerebral malaria.
AB  - BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive
      sequelae up to 2 years after acute disease. The kynurenine pathway of the brain,
      forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid
      (KYNA), has been implicated in long-term cognitive dysfunction in other CNS
      infections. In the present study, the association between the kynurenine pathway
      and neurologic/cognitive complications in children with CM was investigated.
      METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor
      kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala,
      Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were
      compared to CSF cytokine levels, acute and long-term neurologic complications,
      and long-term cognitive impairments. CSF kynurenine and KYNA from eight Swedish
      children without neurological or infectious disease admitted to Astrid Lindgren's
      Children's Hospital were quantified and used for comparison. RESULTS: Children
      with CM had significantly higher CSF concentration of kynurenine and KYNA than
      Swedish children (P < 0.0001 for both), and CSF kynurenine and KYNA were
      positively correlated. In children with CM, CSF kynurenine and KYNA
      concentrations were associated with coma duration in children of all ages (P =
      0.003 and 0.04, respectively), and CSF kynurenine concentrations were associated
      with worse overall cognition (P = 0.056) and attention (P = 0.003) at 12-month
      follow-up in children >=5 years old. CONCLUSIONS: CSF KYNA and kynurenine are
      elevated in children with CM, indicating an inhibition of glutamatergic and
      cholinergic signaling. This inhibition may lead acutely to prolonged coma and
      long-term to impairment of attention and cognition.

PMID- 28754153
TI  - Insulin resistance in a cohort of 5-15 year old children in urban Sri Lanka.
AB  - BACKGROUND: South Asian populations develop insulin resistance from a young age.
      Poor intrauterine growth and increased rates of post natal growth predisposes to
      develop insulin resistance later in life. This study identifies insulin
      resistance and relation to birth weight among a group of 5-15 year old children
      of urban Sri Lanka. METHODS: A cross sectional descriptive study, using two-stage
      probability proportionate cluster sampling technique. After a 12 h overnight
      fast, blood was drawn for fasting blood glucose and insulin. OGTT was performed
      with 2 h random blood glucose. Basic anthropometry was assessed and insulin
      resistance measured by HOMA-IR. RESULTS: Of 309 children (boys 133) 13 (4.2%)
      were obese and 35 (11.3%) were overweight. Eight had impaired glucose homeostasis
      but no diabetes mellitus. The mean (SD) fasting insulin was 37.8 (37.9) and 32.5
      (40.4) pmol/L in girls and boys respectively. 2 h post glucose insulin in girls
      and boys were 258 (324) and 152 (168) pmol/L respectively. The mean HOMA-IR was
      1.1 (1.1) and 0.94 (1.2) for girls and boys respectively. The 4th quartile value
      of HOMA-IR for the whole population was 1.2 (95% CI 1.1, 1.3) and in obese
      children 2.26 (95% CI 2.0, 3.1). Fasting and 2 h insulin and HOMA-IR was not
      affected by birth weight but showed significant difference when compared across
      present BMI tertile with significantly high values in the highest tertile.
      CONCLUSION: Although many children were able to control glucose within normal
      limits, evidence of early development of insulin resistance was seen. Children
      born small but became obese, had the highest risk of developing insulin
      resistance.

PMID- 28754154
TI  - Prognostic value of programmed death-1, programmed death-ligand 1, programmed
      death-ligand 2 expression, and CD8(+) T cell density in primary tumors and
      metastatic lymph nodes from patients with stage T1-4N+M0 gastric adenocarcinoma.
AB  - BACKGROUND: Anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1)
      immunotherapy has been proved to be effective on gastric cancer in ongoing
      clinical trials. However, the value of PD-L1 in predicting responses of patients
      with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some
      studies suggested that intra- and inter-tumoral heterogeneity of PD-L1 expression
      might explain the controversy. This study aimed to analyze the expression of PD
      L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph
      nodes from patients with stage T1-4N+M0 gastric adenocarcinoma to explore the
      heterogeneity of PD-1 signaling pathway molecules. METHODS: In primary tumors and
      metastatic as well as non-metastatic lymph nodes from patients with stage T1
      4N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with
      immunohistochemistry. CD8(+) T-cell density in primary tumors and PD-1 expression
      on CD8(+) T cells were detected with immunofluorescence. Univariate analysis was
      used to determine the prognostic values of them. Cox proportional hazard
      regression model was used to identify independent risk factors that affect
      patients' overall survival and disease-free survival. RESULTS: Among 119 eligible
      patients who had undergone surgical resection, the positive rate of PD-L1 was
      higher in metastatic lymph nodes than in primary tumors (45.4% vs. 38.7%, P =
      0.005); the positive rate of PD-1 on CD8(+) T cells was significantly higher in
      primary tumors and metastatic lymph nodes than in tumor-free lymph nodes (both P
      < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors
      and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes
      from the same patient. Beside, the positive rate of PD-L2 did not show any
      differences between primary tumors and metastatic lymph nodes. In multivariate
      analysis, PD-L1 expression, PD-L2 expression, a low density of CD8(+) T cells in
      primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were
      associated with poor prognosis. CONCLUSION: The expression of PD-L1 is
      heterogeneous in primary tumors and in metastatic lymph nodes from patients with
      stage T1-4N+M0 gastric adenocarcinoma, which might explain the inconsistent
      results in assessing the prognostic value of PD-L1 expression in previous
      studies.

PMID- 28754155
TI  - Magnetic resonance Adenosine perfusion imaging as Gatekeeper of invasive coronary
      intervention (MAGnet): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Current guidelines for the diagnosis and management of patients with
      stable coronary artery disease (CAD) recommend functional stress testing for risk
      stratification prior to revascularization procedures. Cardiac magnetic resonance
      imaging (CMR) is a modality of choice for stress testing because of its
      capability to detect myocardial ischemia sensitively and specifically.
      Nevertheless, evidence from randomized trials evaluating a CMR-based management
      of stable CAD patients in comparison to a more common angiography-based approach
      still is limited. METHODS/DESIGN: Patients presenting themselves with symptoms
      indicating a stable CAD and a class I or IIa indication for diagnostic coronary
      angiography are prospectively screened and enrolled in the study. All subjects
      receive a basic cardiological work-up and guideline-directed medical therapy. A
      1:1 randomization in two groups is being performed. Patients in group 1 undergo
      diagnostic coronary angiography and subsequent revascularization according to
      current guidelines. Subjects in group 2 undergo adenosine stress CMR and in case
      of myocardial ischemia are sent to coronary angiography. Follow-up is planned for
      3 years. During this time, the number of primary endpoints (defined as cardiac
      death and non-fatal myocardial infarction) and unplanned invasive procedures will
      be documented. Furthermore, symptom burden and quality of life will be assessed
      by use of the Seattle Angina Questionnaire. Sample size is calculated to prove
      non-inferiority of the CMR-based approach. DISCUSSION: In case this study is able
      to accomplish its aim to prove non-inferiority of the CMR-based management in
      patients with stable CAD; the importance of this emerging modality may further
      increase. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02580851 .
      Registered on 14 October 2015. Unique Protocol ID: 237/11.

PMID- 28754156
TI  - The process by which perceived autonomy support predicts motivation, intention,
      and behavior for seasonal influenza prevention in Hong Kong older adults.
AB  - BACKGROUND: This study examined the effectiveness of a theoretical framework that
      integrates self-determination theory (SDT) and the theory of planned behavior
      (TPB) in explaining the use of facemasks to prevent seasonal influenza among Hong
      Kong older adults. METHODS: Data were collected at two time points in the winter
      in Hong Kong, during which influenza is most prevalent. At Time 1, older adults
      (N = 141) completed self-report measures of SDT (perceived autonomy support from
      senior center staff, autonomous motivation for influenza prevention) and TPB
      (attitude, subjective norm, perceived behavioral control, and intention for
      influenza prevention) constructs with respect to facemask used to prevent
      infection. Two weeks later, at Time 2, participants' acceptance of a facemask to
      prevent influenza in the presence of an experimenter with flu-like symptoms was
      recorded. RESULTS: Path analysis found that perceived autonomy support of senior
      center staff was positively and significantly linked to autonomous motivation for
      facemask use, which, in turn, was positively related to intentions to wear
      facemasks through the mediation of attitude, subjective norm, and perceived
      behavioral control. However, the effect of intention on facemask use was not
      significant. CONCLUSIONS: Results generally support the proposed framework and
      the findings of previous studies with respect to intention, but the non
      significant intention-behavior relationship may warrant future research to
      examine the reasons for older adults not to wear facemasks to prevent seasonal
      influenza despite having positive intentions to do so.

PMID- 28754157
TI  - Why did you choose psychiatry? a qualitative study of psychiatry trainees
      investigating the impact of psychiatry teaching at medical school on career
      choice.
AB  - BACKGROUND: There is no consensus regarding the optimal content of the
      undergraduate psychiatry curriculum as well as factors contributing to young
      doctors choosing a career in psychiatry. Our aim was to explore factors which had
      influenced psychiatry trainees' attitudes towards mental health and career
      choice. METHOD: Qualitative in-depth interviews with 21 purposively sampled
      London psychiatry trainees analysed using the Framework method. RESULTS: Early
      exposure and sufficient time in undergraduate psychiatry placements were
      important in influencing psychiatry as a career choice and positive role models
      were often very influential. Integration of psychiatry with teaching about
      physical health was viewed positively, although concerns were raised about the
      potential dilution of psychiatry teaching. Foundation posts in psychiatry were
      very valuable in positively impacting career choice. Other suggestions included
      raising awareness at secondary school level, challenging negative attitudes
      amongst all medical educators, and promoting integration within medical
      specialties. CONCLUSIONS: Improvements in teaching psychiatry could improve
      medical attitudes and promote recruitment into psychiatry.

PMID- 28754158
TI  - The impact of sitting time and physical activity on major depressive disorder in
      South Korean adults: a cross-sectional study.
AB  - BACKGROUND: Previous studies have examined associations between sitting time and
      negative health outcomes and mental health. However, the relationship between
      overall sitting time and major depressive disorder (MDD) in South Korea has not
      been studied. This study examined the association between MDD and overall sitting
      time and physical activity in South Koreans. METHODS: Data from the sixth Korean
      National Health and Nutrition Examination Survey (KNHANES), a cross-sectional,
      nationally representative survey, were analyzed. Total participants were 4145 in
      2014. MDD was assessed using the Patient Health Questionnaire (PHQ-9).
      Participants' data regarding self-reported sitting time and physical activity
      were analyzed via multiple logistic regression. RESULTS: Results showed that
      people who sat for 8-10 h (OR: 1.56, 95% CI: 1.15-2.11) or more than 10 h (OR:
      1.71, 95% CI: 1.23-2.39) had increased risk of MDD compared to those who sat for
      less than 5 h a day. Subgroup analysis showed that the strongest effect of
      reported sitting time on risk of MDD was found in men with lower levels of
      physical activity who sat for 8 to 10 h (OR: 3.04, 95% CI: 1.15-8.01) or more
      than 10 h (OR: 3.43, 95% CI: 1.26-9.35). Level of physical activity was not an
      independent predictor for MDD. CONCLUSIONS: Sitting for long periods was
      associated with greater risk of MDD in South Korean adults. Reducing sitting time
      in people with MDD could help to prevent associated physical health problems and
      may improve mental health.

PMID- 28754159
TI  - The role of electrical stimulation in the management of avascular necrosis of the
      femoral head in adults: a systematic review.
AB  - BACKGROUND: Avascular necrosis of the femoral head causes significant morbidity
      and occurs in up to 20,000 people per year. A variety of nonoperative and
      operative measures have been trialled however a definitive treatment algorithm is
      yet to be established. Young adults in many cases have undergone multiple
      surgical procedures in their lifetime with increasing risks of complications.
      Less invasive techniques may help reduce the number of operations required and
      positively influence the natural history of the disease process. Our aim was to
      navigate the literature and examine the results of electrical stimulation of the
      femoral head in avascular necrosis. METHODS: The following defined search
      strategy was used to perform a systematic review using MEDLINE and Google Scholar
      databases: ((avascular necrosis) OR (osteonecrosis)) AND (femoral head) AND
      ((electrical stimulation) OR (capacitive coupling) OR (pulsed electromagnetic
      fields)). Articles were reviewed and data compiled into tables for analysis.
      RESULTS: Fourty six articles were identified with a total of 10 articles meeting
      the inclusion criteria. 8 articles were prospective studies and 2 were
      retrospective. Early Ficat stages showed the best responses to treatment via
      pulsed electromagnetic fields with improvements in both clinical and radiographic
      parameters. Direct current and capacitative coupling have had a more ambiguous
      outcome. CONCLUSIONS: Pulsed electromagnetic fields may have a role in the
      management of early avascular necrosis. The paucity of clinical studies into this
      technique indicates a need for further studies.

PMID- 28754160
TI  - A school-based epidemiological field survey: difficulties in collecting
      psychiatric outcome data in a middle-income country.
AB  - BACKGROUND: Low- and middle-income countries (LMICs) face a lack of
      epidemiological data. The development of high-quality surveys is a key research
      priority in countries such as Brazil. Our aim is to discuss the difficulties in
      conducting a longitudinal epidemiological survey in a pilot study of a school
      based sample in Sao Paulo. METHODS: Data came from a cohort of school-attending
      adolescents in two neighborhoods with different levels of urbanicity in Sao
      Paulo. Students born in 2002 and in the 7th grade during 2014 were recruited from
      nine public schools. Adolescents and caregivers were interviewed separately at
      baseline and at one year follow-up, using several instruments, including the
      Schedule for Affective Disorders and Schizophrenia for School-Age
      Children/Present and Lifetime Version (K-SADS-PL). RESULTS: Achieving unbiased
      sampling, keeping an updated register of participants' contact information, using
      a full clinical interview without an algorithm for its scoring, and maintaining a
      highly-trained research team were among the difficulties faced. CONCLUSION:
      Working closely with community leaders, organizing group efforts to perform
      interviews, using a short, easy to understand instrument and providing some
      reward for participants were identified as alternatives to dealing with these
      difficulties, useful not only in Brazil, but also in other LMICs.

PMID- 28754161
TI  - A cross sectional study of maternal near miss and mortality at a rural tertiary
      centre in southern nigeria.
AB  - BACKGROUND: The study evaluated the pattern of severe maternal outcome, near miss
      indicators and associated patient and healthcare factors at a private referral
      hospital in rural Nigeria. METHODS: This was a cross sectional study conducted
      from September 2014 to August 2015 in Madonna University Teaching Hospital Elele,
      Rivers State, Nigeria. Pregnant and postpartum women were recruited for the study
      using Nigeria near miss network proforma which was adopted from the WHO near miss
      proforma. We explored administrative, patient related and medical delays.
      Statistical analysis was done using SPSS version 20. RESULTS: Of the 262
      deliveries, 5 women died and 52 women had a near miss event. The maternal
      mortality rate was 1908/100,000. The maternal near miss mortality ratio was 11.4:
      1 while the mortality index was 8.8%. Three out of the five deaths that occurred
      were in the age category of 20-24 years. Abortive outcome was the leading cause
      of maternal mortality contributing 2 of the 5 maternal mortality. The severe
      maternal outcome ratio was 218/1000 and maternal near miss incidence ratio was
      198/1000. Hypertensive disorders of pregnancy contributed 16(28.1%) of the 57
      cases with severe maternal outcome while Obstetrics hemorrhage and abortive
      outcome each contributed 14(24.6%). 6(10.5%) received treatment within 30 min of
      diagnosis while 19(33.3%) waited for greater than 240 min before they received
      intervention. There was a statistically significant association between time of
      intervention and final maternal outcome (p-value = 0.003). Administrative delay
      was noted in 20 cases, while patient related delay was noted in 44 cases.
      CONCLUSION: There is a high burden of near miss and unmet need for reproductive
      health services in rural areas of Nigeria. Different levels of delays abound and
      contribute to the disease burden. Periodic reviews will aid in elimination of the
      delays. There should be better communication between different levels of care and
      emphasis should be on early identification and referral of women for prompt
      management.

PMID- 28754162
TI  - Sensitization of ASIC3 by proteinase-activated receptor 2 signaling contributes
      to acidosis-induced nociception.
AB  - BACKGROUND: Tissue acidosis and inflammatory mediators play critical roles in
      pain. Pro-inflammatory agents trypsin and tryptase cleave and activate proteinase
      activated receptor 2 (PAR2) expressed on sensory nerves, which is involved in
      peripheral mechanisms of inflammation and pain. Extracellular acidosis activates
      acid-sensing ion channel 3 (ASIC3) to trigger pain sensation. Here, we show that
      a functional interaction of PAR2 and ASIC3 could contribute to acidosis-induced
      nociception. METHODS: Electrophysiological experiments were performed on both rat
      DRG neurons and Chinese hamster ovary (CHO) cells expressing ASIC3 and PAR2.
      Nociceptive behavior was induced by acetic acid in rats. RESULTS: PAR2-AP, PAR2
      activating peptide, concentration-dependently increased the ASIC3 currents in CHO
      cells transfected with ASIC3 and PAR2. The proton concentration-response
      relationship was not changed, but that the maximal response increased 58.7 +/-
      3.8% after pretreatment of PAR2-AP. PAR2 mediated the potentiation of ASIC3
      currents via an intracellular cascade. PAR2-AP potentiation of ASIC3 currents
      disappeared after inhibition of intracellular G protein, PLC, PKC, or PKA
      signaling. Moreover, PAR2 activation increased proton-evoked currents and spikes
      mediated by ASIC3 in rat dorsal root ganglion neurons. Finally, peripheral
      administration of PAR2-AP dose-dependently exacerbated acidosis-induced
      nocifensive behaviors in rats. CONCLUSIONS: These results indicated that PAR2
      signaling sensitized ASIC3, which may contribute to acidosis-induced nociception.
      These represent a novel peripheral mechanism underlying PAR2 involvement in
      hyperalgesia by sensitizing ASIC3 in primary sensory neurons.

PMID- 28754163
TI  - Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after
      stroke.
AB  - BACKGROUND: Choroid plexus (CP) supports the entry of monocyte-derived
      macrophages (MDMs) to the central nervous system in animal models of traumatic
      brain injury, spinal cord injury, and Alzheimer's disease. Whether the CP is
      involved in the recruitment of MDMs to the injured brain after ischemic stroke is
      unknown. METHODS: Adult male C57BL/6 mice were subjected to focal cortical
      ischemia by permanent occlusion of the distal branch of the right middle cerebral
      artery. Choroid plexus tissues were collected and analyzed for Vcam1, Madcam1,
      Cx3cl1, Ccl2, Nt5e, and Ifngamma expression at different timepoints after stroke
      using qPCR. Changes of MDMs in CP and cerebrospinal fluid (CSF) at 1 day and 3
      days after stroke were analyzed using flow cytometry. Infiltration of MDMs into
      CP and CSF were validated using beta-actin-GFP chimeric mice and Fgd5-CreERT2 x
      Lox-stop-lox-Tomato mice. CD115+ monocytes were isolated using a magnetic cell
      separation system from bone marrow of Cx3cr1-GFP or wild-type C57BL/6 donor mice.
      The freshly isolated monocytes or M2-like MDMs primed in vitro with IL4 and IL13
      were stereotaxically injected into the lateral ventricle of stroke-affected mice
      to trace for their migration into ischemic hemisphere or to assess their effect
      on post-stroke recovery using open field, corridor, and active avoidance
      behavioral tests. RESULTS: We found that CP responded to cortical stroke by
      upregulation of gene expression for several possible mediators of MDM trafficking
      and, concomitantly, MDMs increased in CP and cerebrospinal fluid (CSF). We then
      confirmed that MDMs infiltrated from blood into CP and CSF after the insult using
      beta-actin-GFP chimeric mice and Fgd5-CreERT2 x Lox-stop-lox-Tomato mice. When
      MDMs were directly administered into CSF following stroke, they homed to the
      ischemic hemisphere. If they had been primed in vitro prior to their
      administration to become M2-like macrophages, they promoted post-stroke recovery
      of motor and cognitive function without influencing infarct volume. CONCLUSIONS:
      Our findings suggest the possibility that autologous transplantation of M2-like
      MDMs into CSF might be developed into a new strategy for promoting recovery also
      in patients with stroke.

PMID- 28754164
TI  - Data-driven interdisciplinary mathematical modelling quantitatively unveils
      competition dynamics of co-circulating influenza strains.
AB  - BACKGROUND: Co-circulation of influenza strains is common to seasonal epidemics
      and pandemic emergence. Competition was considered involved in the vicissitudes
      of co-circulating influenza strains but never quantitatively studied at the human
      population level. The main purpose of the study was to explore the competition
      dynamics of co-circulating influenza strains in a quantitative way. METHODS: We
      constructed a heterogeneous dynamic transmission model and ran the model to fit
      the weekly A/H1N1 influenza virus isolation rate through an influenza season. The
      construction process started on the 2007-2008 single-clade influenza season and,
      with the contribution from the clade-based A/H1N1 epidemiological curves,
      advanced to the 2008-2009 two-clade influenza season. Pearson method was used to
      estimate the correlation coefficient between the simulated epidemic curve and the
      observed weekly A/H1N1 influenza virus isolation rate curve. RESULTS: The model
      found the potentially best-fit simulation with correlation coefficient up to 96%
      and all the successful simulations converging to the best-fit. The annual
      effective reproductive number of each co-circulating influenza strain was
      estimated. We found that, during the 2008-2009 influenza season, the annual
      effective reproductive number of the succeeding A/H1N1 clade 2B-2, carrying H275Y
      mutation in the neuraminidase, was estimated around 1.65. As to the preceding
      A/H1N1 clade 2C-2, the annual effective reproductive number would originally be
      equivalent to 1.65 but finally took on around 0.75 after the emergence of clade
      2B-2. The model reported that clade 2B-2 outcompeted for the 2008-2009 influenza
      season mainly because clade 2C-2 suffered from a reduction of transmission
      fitness of around 71% on encountering the former. CONCLUSIONS: We conclude that
      interdisciplinary data-driven mathematical modelling could bring to light the
      transmission dynamics of the A/H1N1 H275Y strains during the 2007-2009 influenza
      seasons worldwide and may inspire us to tackle the continually emerging drug
      resistant A/H1N1pdm09 strains. Furthermore, we provide a prospective approach
      through mathematical modelling to solving a seemingly unintelligible problem at
      the human population level and look forward to its application at molecular level
      through bridging the resolution capacities of related disciplines.

PMID- 28754165
TI  - Increasing health policy and systems research capacity in low- and middle-income
      countries: results from a bibliometric analysis.
AB  - BACKGROUND: For 20 years, substantial effort has been devoted to catalyse health
      policy and systems research (HPSR) to support vulnerable populations and resource
      constrained regions through increased funding, institutional capacity-building
      and knowledge production; yet, participation from low- and middle-income
      countries (LMICs) is underrepresented in HPSR knowledge production. METHODS: A
      bibliometric analysis of HPSR literature was conducted using a high-level keyword
      search. Health policy and/or health systems literature with a topic relevant to
      LMICs and whose lead author's affiliation is in an LMIC were included for
      analysis. The trends in knowledge production from 1990 to 2015 were examined to
      understand how investment in HPSR benefits those it means to serve. RESULTS: The
      total number of papers published in PubMed increases each year. HPSR publications
      represent approximately 10% of these publications, but this percentage is
      increasing at a greater rate than PubMed publications overall and the discipline
      is holding this momentum. HPSR publications with topics relevant to LMICs and an
      LMIC-affiliated lead authors (specifically from low-income countries) are
      increasing at a greater rate than any other category within the scope of this
      analysis. CONCLUSIONS: While the absolute number of publications remains low,
      lead authors from an LMIC have participated exponentially in the life and
      biomedical sciences (PubMed) since the early 2000s. HPSR publications with a
      topic relevant to LMICs and an LMIC lead author continue to increase at a greater
      rate than the life and biomedical science topics in general. This correlation is
      likely due to increased capacity for research within LMICs and the support for
      publications surrounding large HPSR initiatives. These findings provide strong
      evidence that continued support is key to the longevity and enhancement of HPSR
      toward its mandate.

PMID- 28754166
TI  - Male reproductive health challenges: appraisal of wives coping strategies.
AB  - BACKGROUND: Systematic studies on the association between men's sexual
      dysfunction (low sexual desire, ejaculation disorders, erectile dysfunctions,
      genital ulcers, testicular disorders, prostate cancer or sexually transmitted
      infections) and marital conflict are emerging. However, the coping strategies
      adopted by wives in such circumstances are not commonly reported in the
      literature. Male sexual functioning is vital to the marital relationship, lack of
      it can result in intolerable cohabitation or relationship breakdown, and could
      also cause infertility, infidelity, and arouse stigma in Nigeria. The
      understanding of coping strategies by female partners could guide in the
      counselling and treatment of men's sexual health problems. Effective coping has
      the potential to lessen or prevent negative outcomes, and thereby could reduce
      marital conflict. OBJECTIVES: This study examined the coping strategies adopted
      by women whose husbands have reproductive health challenges in two of the five
      states with the highest proportion of divorce/separation in Nigeria. METHODS:
      Four focus group discussions were conducted in two local government areas. The
      women were recruited from a quantitative couple-study for men with sexual health
      problems. Focus group responses were transcribed and analysed using systematic
      content-analysis with thematic organisation of the summaries and systematic
      typologies of participants' responses. RESULTS: The results revealed the coping
      strategies employed by women in this environment: seeking guidance from their
      religious leaders and family doctors, physical-sexual-therapy, abstinence and
      concubinage. The participants indicated that they encountered difficulties in
      discussing their husbands' sexual health problems with a third party. CONCLUSION:
      The study concludes that husband's sexual ability is crucial to the sustenance of
      the marital relationship. Religious leaders and family doctors often serve as
      mediators to husband-wife conflict management. Counselling is recommended in
      cases of sexual health problems. Husbands should be encouraged to seek treatment
      and share their sexual challenges with their spouse. The medical officers and
      religious leaders could also be trained in family-conflict management.

PMID- 28754167
TI  - Antivirals for allosteric inhibition of Zika virus using a homology model and
      experimentally determined structure of envelope protein.
AB  - OBJECTIVE: An approach to inhibiting enveloped flaviviruses is to deter the
      ability of the envelope protein(s) binding onto glycoproteins. In previous work,
      using a small ~100-amino acid homology model of Zika virus envelope protein
      (ZVEP), we proved the susceptibility of Zika virus to inhibition. In this work,
      we verify the efficacy of the homology model based antiviral search method using
      a larger protein (>400 amino acids) and comparing the results with the
      experimentally determined one (PDB ID:5IRE). RESULTS: By examining how glycan
      molecules, small-molecule probes and screened ligands that have a high affinity
      to ZVEP, we report the mechanics of ZVEP to inhibition via allosteric blockage of
      the glycan-binding domain while proposing even more possibly potent inhibitors.
      The small molecular probes based study using the homology model and subsequently
      verified using actual experimental structure, 5IRE, revealed that ZVEP is
      druggable. A pharmacophore analysis followed by screening showed at least four
      ligands that allosterically binds to the glycan binding domain constituted by
      residues VAL 153 and ASN 154 in 5IRE. Based on further selection criteria
      ZINC40621658 was identified to have high potential to be a strong antiviral
      candidate for Zika virus inhibition.

PMID- 28754168
TI  - Improvement of bone mineral density after enzyme replacement therapy in Chinese
      late-onset Pompe disease patients.
AB  - OBJECTIVE: Late-onset Pompe disease (LOPD) is a lysosomal storage disease
      resulted from deficiency of the enzyme acid alpha-glucosidase. Patients usually
      develop a limb-girdle pattern of myopathy and respiratory impairment, and enzyme
      replacement therapy (ERT) is the only specific treatment available. Recently,
      LOPD has been associated with low bone mineral density (BMD), but the effect of
      ERT on BMD is inconclusive. In this report we described our early observations on
      the change of BMD after ERT in Chinese LOPD patients. RESULTS: We studied four
      Chinese LOPD patients with different severities of myopathy. All were
      underweight, and three had osteoporosis at baseline. We found significant weight
      gain in three patients after ERT and all four patients showed improvement in BMD.
      The biggest improvement, 84.4% increase in BMD, was seen in a lady with the most
      prominent weight recovery. Our results suggest that ERT improves BMD in Chinese
      LOPD and weight gain could be a major contributor to this effect.

PMID- 28754169
TI  - Type B ankle fractures: a retrospective study of longer-term outcomes.
AB  - OBJECTIVES: Ankle fractures are common and can be treated with or without
      surgery. The aim of the present study was to compare patient reported outcomes
      between patients who sustained an Orthopaedic Trauma Association type 44-B1 ankle
      fracture who had either surgical or non-surgical fixation. RESULTS: Forty-six
      people were recruited; 38 were treated non-surgically and 8 were treated
      surgically. Mean follow-up time was 24 and 25 months for surgical and non
      surgical groups respectively. Baseline characteristics were similar between the
      two groups. On unadjusted analysis, there was no significant difference between
      the two groups with respect to any outcome. After adjusting for age and gender,
      the surgical group had a significantly lower outcome score with respect to the
      FAOQ. Surgical management was associated with a significantly lower patient
      reported ankle function compared to non-surgical management for the treatment of
      patients with type 44-B1 ankle fracture after adjusting for age and gender.
      However, there was no significant difference between the two groups with respect
      to the general health outcomes or adverse events. Higher-level evidence is
      required to inform optimal practice for this common fracture.

PMID- 28754170
TI  - Pattern and predictors of medicine use among households in Gondar Town,
      northwestern Ethiopia: a community-based medicine utilization study.
AB  - BACKGROUND: Medicine use can be influenced by several factors. Health managers
      need specific information about irrational use of medicines, in order to identify
      opportunities to enhance rational use of medicines in their communities. This
      study aimed to assess the pattern and factors associated with household medicine
      use in Gondar town, northwestern Ethiopia. METHODS: An interviewer-administered
      cross-sectional survey was conducted on 771 households, carried out between 5
      April and 6 May 2015. The questionnaire contained items focusing on different
      aspects of medicine use in the households. The analysis involved descriptive
      summary and binary logistic regression test, which assessed association of
      independent variables with medicine use. RESULTS: Of the households interviewed,
      22.4% (173/771) disclosed the presence of at least one chronic disease in the
      family; while 49.2% reported the use of medicine in the one month prior to the
      study. Almost all of the households (92.6%) reported a habit of discontinuing
      medicines, and 17.8% disclosed a practice of sharing medicines with household
      members and others. Level of education, presence of health professionals, and
      individuals with chronic illness in the households were linked to increased
      likelihood of reporting medicine use. Discarding leftover medicines with garbage
      (56.7%) was the principal means of disposal reported by the households.
      CONCLUSIONS: A high proportion of reported medicine use, together with problems
      such as sharing with other people and leaving medicines unfinished were found
      among the households in the study.

PMID- 28754171
TI  - Stab injury to the preauricular region with laceration of the external carotid
      artery without involvement of the facial nerve: a case report.
AB  - BACKGROUND: Open injuries to the face involving the external carotid artery are
      uncommon. These injuries are normally associated with laceration of the facial
      nerve because this nerve is more superficial than the external carotid artery.
      Hence, external carotid artery lesions are usually associated with facial nerve
      dysfunction. We present an unusual case report in which the patient had an injury
      to this artery with no facial nerve compromise. CASE PRESENTATION: A 25-year-old
      Portuguese man sustained a stab wound injury to his right preauricular region
      with a broken glass. Immediate profuse bleeding ensued. Provisory tamponade of
      the wound was achieved at the place of aggression by two off-duty doctors. He was
      initially transferred to a district hospital, where a large arterial bleeding was
      observed and a temporary compressive dressing was applied. Subsequently, the
      patient was transferred to a tertiary hospital. At admission in the emergency
      room, he presented a pulsating lesion in the right preauricular region and slight
      weakness in the territory of the inferior buccal branch of the facial nerve. The
      physical examination suggested an arterial lesion superficial to the facial
      nerve. However, in the operating theater, a section of the posterior and lateral
      flanks of the external carotid artery inside the parotid gland was identified. No
      lesion of the facial nerve was observed, and the external carotid artery was
      repaired. To better understand the anatomical rationale of this uncommon clinical
      case, we dissected the preauricular region of six cadavers previously injected
      with colored latex solutions in the vascular system. A small triangular space
      between the two main branches of division of the facial nerve in which the
      external carotid artery was not covered by the facial nerve was observed
      bilaterally in all cases. CONCLUSIONS: This clinical case illustrates that, in a
      preauricular wound, the external carotid artery can be injured without facial
      nerve damage. However, no similar description was found in the reviewed
      literature, which suggests that this must be a very rare occurrence. According to
      the dissection study performed, this is due to the existence of a triangular
      space between the cervicofacial and temporofacial nerve trunks in which the
      external carotid artery is not covered by the facial nerve or its branches.

PMID- 28754172
TI  - A quantitative and qualitative comparison of illumina MiSeq and 454 amplicon
      sequencing for genotyping the highly polymorphic major histocompatibility complex
      (MHC) in a non-model species.
AB  - BACKGROUND: High-throughput sequencing enables high-resolution genotyping of
      extremely duplicated genes. 454 amplicon sequencing (454) has become the standard
      technique for genotyping the major histocompatibility complex (MHC) genes in non
      model organisms. However, illumina MiSeq amplicon sequencing (MiSeq), which
      offers a much higher read depth, is now superseding 454. The aim of this study
      was to quantitatively and qualitatively evaluate the performance of MiSeq in
      relation to 454 for genotyping MHC class I alleles using a house sparrow (Passer
      domesticus) dataset with pedigree information. House sparrows provide a good
      study system for this comparison as their MHC class I genes have been studied
      previously and, consequently, we had prior expectations concerning the number of
      alleles per individual. RESULTS: We found that 454 and MiSeq performed equally
      well in genotyping amplicons with low diversity, i.e. amplicons from individuals
      that had fewer than 6 alleles. Although there was a higher rate of failure in the
      454 dataset in resolving amplicons with higher diversity (6-9 alleles), the same
      genotypes were identified by both 454 and MiSeq in 98% of cases. CONCLUSIONS: We
      conclude that low diversity amplicons are equally well genotyped using either 454
      or MiSeq, but the higher coverage afforded by MiSeq can lead to this approach
      outperforming 454 in amplicons with higher diversity.

PMID- 28754173
TI  - A randomized, double-blind, placebo-controlled trial on the role of preemptive
      analgesia with acetaminophen [paracetamol] in reducing headache following
      electroconvulsive therapy [ECT].
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is a safe and efficient treatment for
      several severe psychiatric disorders, but its use is limited by side effects.
      Post-ECT headache is one of the commonest side effects. Preemptive analgesia is
      effective in post-surgical pain management. The most commonly used analgesic is
      acetaminophen (paracetamol). However, acetaminophen as a preemptive analgesic for
      post-ECT headache has not been studied adequately. This study was conducted to
      compare the incidence and severity of post-ECT headache in patients who were
      administered acetaminophen pre-ECT with a placebo group. METHODS: This study was
      a randomised, double-blind, placebo-controlled trial. Sixty-three patients
      received 1 g acetaminophen and 63 patients received a placebo identical to
      acetaminophen. The incidence and severity of headache 2 h before and after ECT
      were compared between placebo and acetaminophen groups. The severity was measured
      using a visual analog scale. Generalised linear models were used to evaluate
      variables associated with post ECT headache. RESULTS: Demographic and clinical
      variables of placebo and acetaminophen groups were comparable except for the
      energy level used to induce a seizure. Higher proportion of the placebo group
      (71.4%) experienced post-ECT headache when compared to the acetaminophen group (p
      < 0.001). The median pain score for headache was 0 (Inter quartile range: 0-2) in
      acetaminophen group whereas the score was 2 (IQR: 0-4) in placebo group (P <
      0.001). Model fitting showed that the administration of acetaminophen is
      associated with less post-ECT headache (odds ratio = 0.23, 95% CI: 0.11-0.48, P <
      0.001). CONCLUSION: A significant reduction was seen in both the incidence and
      severity of post-ECT headache with preemptive analgesia with acetaminophen. TRIAL
      REGISTRATION: Ethical approval was granted by an Ethic review committee,
      University of Kelaniya, Sri Lanka (P/166/10/2015) and the trial was registered in
      the Sri Lanka Clinical Trials Registry ( SLCTR/2015/27 ).

PMID- 28754174
TI  - RNAi therapy to the wall of arteries and veins: anatomical, physiologic, and
      pharmacological considerations.
AB  - BACKGROUND: Cardiovascular disease remains a major health care challenge. The
      knowledge about the underlying mechanisms of the respective vascular disease
      etiologies has greatly expanded over the last decades. This includes the
      contribution of microRNAs, endogenous non-coding RNA molecules, known to vastly
      influence gene expression. In addition, short interference RNA has been
      established as a mechanism to temporarily affect gene expression. This review
      discusses challenges relating to the design of a RNA interference therapy
      strategy for the modulation of vascular disease. Despite advances in medical and
      surgical therapies, atherosclerosis (ATH), aortic aneurysms (AA) are still
      associated with high morbidity and mortality. In addition, intimal hyperplasia
      (IH) remains a leading cause of late vein and prosthetic bypass graft failure.
      Pathomechanisms of all three entities include activation of endothelial cells
      (EC) and dedifferentiation of vascular smooth muscle cells (VSMC). RNA
      interference represents a promising technology that may be utilized to silence
      genes contributing to ATH, AA or IH. Successful RNAi delivery to the vessel wall
      faces multiple obstacles. These include the challenge of cell specific, targeted
      delivery of RNAi, anatomical barriers such as basal membrane, elastic laminae in
      arterial walls, multiple layers of VSMC, as well as adventitial tissues. Another
      major decision point is the route of delivery and potential methods of
      transfection. A plethora of transfection reagents and adjuncts have been
      described with varying efficacies and side effects. Timing and duration of RNAi
      therapy as well as target gene choice are further relevant aspects that need to
      be addressed in a temporo-spatial fashion. CONCLUSIONS: While multiple
      preclinical studies reported encouraging results of RNAi delivery to the vascular
      wall, it remains to be seen if a single target can be sufficient to the achieve
      clinically desirable changes in the injured vascular wall in humans. It might be
      necessary to achieve simultaneous and/or sequential silencing of multiple,
      synergistically acting target genes. Some advances in cell specific RNAi delivery
      have been made, but a reliable vascular cell specific transfection strategy is
      still missing. Also, off-target effects of RNAi and unwanted effects of
      transfection agents on gene expression are challenges to be addressed. Close
      collaborative efforts between clinicians, geneticists, biologists, and chemical
      and medical engineers will be needed to provide tailored therapeutics for the
      various types of vascular diseases.

PMID- 28754175
TI  - Case report: term birth after fertility-sparing treatments for stage IB1 small
      cell neuroendocrine carcinoma of the cervix.
AB  - BACKGROUND: Advances in cervical cancer management for childbearing women have
      led to less radical approaches. Use of fertility-sparing treatment to treat small
      cell neuroendocrine carcinoma (SCNEC) is challenging owing to the aggressive
      nature of the disease, even in early stage disease. CASE PRESENTATION: A 25-year
      old nulligravida woman presented with malodorous vaginal discharge and was
      diagnosed to have an exophytic cervical SCNEC. A magnetic resonance image scan
      showed no evidence of parametrial invasion or distant metastasis. Clinical
      staging allocated her to stage IB1 disease. She underwent radical abdominal
      trachelectomy for reproductive purpose. Preoperative and postoperative
      chemotherapy with ifosfamide/etoposide/cisplatin combining gonadotropin-releasing
      hormone agonist were administered. She had a spontaneous, uneventful pregnancy
      and successfully delivered a term baby via cesarean section 7 years after
      treatment. CONCLUSION: To our knowledge, we describe the first success in
      offering a fertility-preserving multimodality strategy to present favorable
      oncologic, reproductive, and obstetric outcomes in a fertile woman of stage I
      SCNEC. Individualized multimodality therapy may be utilized in specific patients
      with early-stage cervical cancer to preserve their fertility.

PMID- 28754177
TI  - Bacteriological assessment of stethoscopes used by healthcare workers in a
      tertiary care centre of Nepal.
AB  - OBJECTIVE: Stethoscope is a medical device universally used by health care
      workers. Stethoscope may transmit pathogens among patients and health care
      workers if it is not disinfected. The objective of this study was to, determine
      the level of stethoscope contamination used by health care workers, survey the
      practices of disinfecting the stethoscope, identify various microorganisms and
      assess their role as potential pathogens and determine the effectiveness of 70%
      ethanol as a disinfecting agent. RESULTS: This was a cross-sectional study
      conducted in the department of Microbiology, Chitwan Medical College, Bharatpur,
      Nepal. Stethoscopes of 122 health care workers from different departments were
      included in this study. Out of a total 122 diaphragms, 88 (72.1%) were colonized.
      Only 71 (58.1%) bells and 152 earpieces (66.2%) were contaminated. Micrococcus
      and coagulase negative staphylococci were predominantly isolated species. The
      contamination was lowest among stethoscopes cleaned after touching every patient
      (11.5%) and the difference is statistically significant (P < 0.0001).
      Significantly lower level of contamination (13.6%) were found on stethoscopes
      cleaned everyday (P < 0.0001). Only 8.5% stethoscope showed growth with decreased
      number of colonies after disinfecting the stethoscopes with 70% ethanol. Thus,
      demonstrating the effectiveness of disinfection.

PMID- 28754176
TI  - Genome-wide gene by lead exposure interaction analysis identifies UNC5D as a
      candidate gene for neurodevelopment.
AB  - BACKGROUND: Neurodevelopment is a complex process involving both genetic and
      environmental factors. Prenatal exposure to lead (Pb) has been associated with
      lower performance on neurodevelopmental tests. Adverse neurodevelopmental
      outcomes are more frequent and/or more severe when toxic exposures interact with
      genetic susceptibility. METHODS: To explore possible loci associated with
      increased susceptibility to prenatal Pb exposure, we performed a genome-wide gene
      environment interaction study (GWIS) in young children from Mexico (n = 390) and
      Bangladesh (n = 497). Prenatal Pb exposure was estimated by cord blood Pb
      concentration. Neurodevelopment was assessed using the Bayley Scales of Infant
      Development. RESULTS: We identified a locus on chromosome 8, containing UNC5D,
      and demonstrated evidence of its genome-wide significance with mental composite
      scores (rs9642758, p meta = 4.35 * 10-6). Within this locus, the joint effects of
      two independent single nucleotide polymorphisms (SNPs, rs9642758 and rs10503970)
      had a p-value of 4.38 * 10-9 for mental composite scores. Correlating GWIS
      results with in vitro transcriptomic profiles identified one common gene, SLC1A5,
      which is involved in synaptic function, neuronal development, and excitotoxicity.
      Further analysis revealed interconnected interactions that formed a large network
      of 52 genes enriched with oxidative stress genes and neurodevelopmental genes.
      CONCLUSIONS: Our findings suggest that certain genetic polymorphisms within/near
      genes relevant to neurodevelopment might modify the toxic effects of Pb exposure
      via oxidative stress.

PMID- 28754178
TI  - Evaluation of microvascular endothelial function in patients with infective
      endocarditis using laser speckle contrast imaging and skin video-capillaroscopy:
      research proposal of a case control prospective study.
AB  - OBJECTIVE: Infective endocarditis is a severe condition with high in-hospital and
      5-year mortality. There is increasing incidence of infective endocarditis, which
      may be related to healthcare and changes in prophylaxis recommendations regarding
      oral procedures. Few studies have evaluated the microcirculation in patients with
      infective endocarditis, and so far, none have utilized laser-based technology or
      evaluated functional capillary density. The aim of the study is to evaluate the
      changes in the systemic microvascular bed of patients with both acute and
      subacute endocarditis. This is a cohort study that will include adult patients
      with confirmed active infective endocarditis according to the modified Duke
      criteria who were admitted to our center for treatment. A control group of sex-
      and age-matched healthy volunteers will be included. Functional capillary
      density, which is defined as the number of spontaneously perfused capillaries per
      square millimeter of skin, will be assessed by video-microscopy with an epi
      illuminated fiber optic microscope. Capillary recruitment will be evaluated using
      post-occlusive reactive hyperemia. Microvascular flow will be evaluated in the
      forearm using a laser speckle contrast imaging system for the noninvasive and
      continuous measurement of cutaneous microvascular perfusion changes. Laser
      speckle contrast imaging will be used in combination with skin iontophoresis of
      acetylcholine, an endothelium-dependent vasodilator, or sodium nitroprusside
      (endothelium independent) to test microvascular reactivity. RESULTS: The present
      study will contribute to the investigation of microcirculatory changes in
      infective endocarditis and possibly lead to an earlier diagnosis of the condition
      and/or determination of its severity and complications. Trial registration
      ClinicalTrials.gov ID: NCT02940340.

PMID- 28754179
TI  - Cognitive behavioural therapy attenuates the enhanced early facial stimuli
      processing in social anxiety disorders: an ERP investigation.
AB  - BACKGROUND: Previous studies of patients with social anxiety have demonstrated
      abnormal early processing of facial stimuli in social contexts. In other words,
      patients with social anxiety disorder (SAD) tend to exhibit enhanced early facial
      processing when compared to healthy controls. Few studies have examined the
      temporal electrophysiological event-related potential (ERP)-indexed profiles when
      an individual with SAD compares faces to objects in SAD. Systematic comparisons
      of ERPs to facial/object stimuli before and after therapy are also lacking. We
      used a passive visual detection paradigm with upright and inverted faces/objects,
      which are known to elicit early P1 and N170 components, to study abnormal early
      face processing and subsequent improvements in this measure in patients with SAD.
      METHODS: Seventeen patients with SAD and 17 matched control participants
      performed a passive visual detection paradigm task while undergoing EEG. The
      healthy controls were compared to patients with SAD pre-therapy to test the
      hypothesis that patients with SAD have early hypervigilance to facial cues. We
      compared patients with SAD before and after therapy to test the hypothesis that
      the early hypervigilance to facial cues in patients with SAD can be alleviated.
      RESULTS: Compared to healthy control (HC) participants, patients with SAD had
      more robust P1-N170 slope but no amplitude effects in response to both upright
      and inverted faces and objects. Interestingly, we found that patients with SAD
      had reduced P1 responses to all objects and faces after therapy, but had
      selectively reduced N170 responses to faces, and especially inverted faces.
      Interestingly, the slope from P1 to N170 in patients with SAD was flatter post
      therapy than pre-therapy. Furthermore, the amplitude of N170 evoked by the facial
      stimuli was correlated with scores on the interaction anxiousness scale (IAS)
      after therapy. CONCLUSIONS: Our results did not provide electrophysiological
      support for the early hypervigilance hypothesis in SAD to faces, but confirm that
      cognitive-behavioural therapy can reduce the early visual processing of faces.
      These findings have potentially important therapeutic implications in the
      assessment and treatment of social anxiety. Trial registration HEBDQ2014021.

PMID- 28754180
TI  - Spatio-temporal analysis of the incidence of colorectal cancer in Guangzhou, 2010
      2014.
AB  - INTRODUCTION: Colorectal cancer (CRC) is a common type of neoplasm. This study
      examined the spatio-temporal distribution of the CRC incidence in Guangzhou
      during 2010-2014. METHODS: Colorectal cancer incidence data were obtained from
      the Guangzhou Cancer Registry System. Spatial autocorrelation analysis and a
      retrospective spatio-temporal scan were used to assess the spatio-temporal
      cluster distribution of CRC cases. RESULTS: A total of 14,618 CRC cases were
      registered in Guangzhou during 2010-2014, with a crude incidence of 35.56/100,000
      and an age-standardized rate of incidence by the world standard population
      (ASRIW) of 23.58/100,000. The crude incidence increased by 19.70% from 2010
      (32.88/100,000) to 2014 (39.36/100,000) with an average annual percentage change
      (AAPC) of 4.33%. The AAPC of ASRIW was not statistically significant. The spatial
      autocorrelation analysis revealed a CRC incidence hot spot in central urban areas
      in Guangzhou City, which included 25 streets in southwestern Baiyun District,
      northwestern Haizhu District, and the border region between Liwan and Yuexiu
      Districts. Three high- and five low-incidence clusters were identified according
      to spatio-temporal scan of CRC incidence clusters. The high-incidence clusters
      were located in central urban areas including the border regions between Baiyun,
      Haizhu, Liwan, and Yuexiu Districts. CONCLUSIONS: This study revealed the spatio
      temporal cluster pattern of the incidence of CRC in Guangzhou. This information
      can inform allocation of health resources for CRC screening.

PMID- 28754181
TI  - A march toward scientific literacy.

PMID- 28754182
TI  - Interpreting and Extrapolating Study Results.

PMID- 28754183
TI  - Authors' response.

PMID- 28754184
TI  - Malocclusions in young children: Does breast-feeding really reduce the risk? A
      systematic review and meta-analysis.
AB  - BACKGROUND: Researchers have purported that breast-feeding can decrease the risk
      of malocclusions. The authors studied the relationship of breast-feeding on
      malocclusions in young children by means of conducting a systematic review of
      association (etiology). TYPES OF STUDIES REVIEWED: The authors used a 3-step
      search strategy, including electronic searches. They considered studies whose
      investigators included healthy children with primary dentition with a history of
      breast-feeding and in which the study investigators had assessed specific
      malocclusion outcomes to be eligible for inclusion in this review. The authors
      considered prospective and retrospective (longitudinal) studies, case-control
      studies, and analytical cross-sectional studies. Two of the authors, using
      standardized instruments, independently assessed the methodological quality and
      extracted data from the included studies. For situations for which there were a
      sufficient number of studies, the authors conducted meta-analyses using the
      random-effects model, supplemented with the fixed-effects model in situations for
      which statistical heterogeneity was 50% or less, assessed using the I2 statistic.
      RESULTS: The authors identified 7 studies that were included in the review. They
      found that children who had breast-fed suboptimally had an increased risk of
      developing malocclusions and that a strong and significant association existed
      between a shorter duration of breast-feeding (less than 12 months) and the
      development of an anterior open bite (n = 1,875; risk ratio, 3.58; 95% confidence
      interval, 2.55 to 5.03; P < .00001) and a class II canine relationship (n =
      1,203; risk ratio, 1.65; 95% confidence interval, 1.38 to 1.97; P < .00001).
      CONCLUSIONS: Young children with a history of suboptimal breast-feeding have a
      higher prevalence and risk ratio for malocclusions. These children have an
      increased risk of developing a class II canine relationship, posterior crossbite,
      and anterior open bite. PRACTICAL IMPLICATIONS: Dental health care professionals
      should continue to encourage and promote breast-feeding; however, patients should
      be aware that children still can develop malocclusions, despite having received
      optimal breast-feeding, owing to the multifactorial etiology of malocclusions.

PMID- 28754185
TI  - Association between maxillary anterior supernumerary teeth and impacted incisors
      in mixed dentition.
AB  - BACKGROUND: Few researchers have investigated the relationship between
      supernumerary teeth (ST) and impacted incisors. The authors investigated the
      relationship between ST and impacted incisors in the maxillary anterior area in
      the mixed dentition. METHODS: Using cone-beam computed tomography, the authors
      diagnosed 417 ST among 294 patients (age range, 6-12 years; 220 boys and 74
      girls). The number, morphology, growth orientation, and position of ST were
      recorded along with the presence of impacted incisors. RESULTS: The authors
      reported that 23.1% of patients having ST (n = 68; mean [standard deviation] age
      8.5 [1.6] years) also had impacted incisors. Morphology (molariform and
      odontomelike), growth orientation (normal and no orientation), and position
      (coronal) of the ST were significantly associated with impacted incisors (P < .05
      for all). An increase of 1 year in age was associated with a decreased risk of
      having ST accompanied by impacted incisors (odds ratio, 0.76; 95% confidence
      interval, 0.63 to 0.92). An increase of 1 ST more than doubled the risk of having
      an impacted incisor (odds ratio, 2.39; 95% confidence interval, 1.44 to 3.96).
      CONCLUSIONS: In this population, the number, morphology, growth orientation, and
      position of ST as well as the patient's age were associated with impacted
      incisors in the maxillary anterior area during the mixed dentition. PRACTICAL
      IMPLICATIONS: The presence and morphology of ST should alert the clinician to the
      increased likelihood of having impacted incisors and the need for early diagnosis
      and appropriate treatment.

PMID- 28754186
TI  - Effective strategies for triaging emergencies.

PMID- 28754187
TI  - What do you do when a parent does not obtain needed treatment for a minor child?

PMID- 28754188
TI  - Adolescents with body image concerns and a propensity for somatization reported
      more frequent temporomandibular joint clicking.

PMID- 28754189
TI  - Progress and Works in Progress: Update on Flavivirus Vaccine Development.
AB  - Most areas of the globe are endemic for at least one flavivirus, putting billions
      at risk for infection. This diverse group of viral pathogens causes a range of
      manifestations in humans from asymptomatic infection to hemorrhagic fever to
      encephalitis to birth defects and even death. Many flaviviruses are transmitted
      by mosquitos and have expanded in geographic distribution in recent years, with
      dengue virus being the most prevalent, infecting approximately 400 million people
      each year. The explosive emergence of Zika virus in Latin America in 2014
      refocused international attention on this medically important group of viruses.
      Meanwhile, yellow fever has caused major outbreaks in Africa and South America
      since 2015 despite a reliable vaccine. There is no vaccine for Zika yet, and the
      only licensed dengue vaccine performs suboptimally in certain contexts. Further
      lessons are found when considering the experience with Japanese encephalitis
      virus, West Nile virus, and tickborne encephalitis virus, all of which now have
      protective vaccination in human or veterinary populations. Thus, vaccination is a
      mainstay of public health strategy for combating flavivirus infections; however,
      numerous challenges exist along the path from development to delivery of a
      tolerable and effective vaccine. Nevertheless, intensification of investment and
      effort in this area holds great promise for significantly reducing the global
      burden of disease attributable to flavivirus infection.

PMID- 28754190
TI  - Community over-the-counter management of burns wounds: Is there an education gap?

PMID- 28754191
TI  - Biosimilars: an optimistic outlook, but vigilance is needed.

PMID- 28754192
TI  - Early fibrinogen-concentrate administration in management of trauma-induced
      coagulopathy - Authors' reply.

PMID- 28754193
TI  - Early fibrinogen-concentrate administration in management of trauma-induced
      coagulopathy.

PMID- 28754194
TI  - Looking behind the data curtain.

PMID- 28754195
TI  - Important considerations when selecting, applying, and interpreting readability
      formulas.

PMID- 28754196
TI  - Food Waste: A Solvable Problem.

PMID- 28754197
TI  - Creating Images with Impact: Food Photography Tips from MyPlate.

PMID- 28754198
TI  - Practice Paper of the Academy of Nutrition and Dietetics: Classic and Modified
      Ketogenic Diets for Treatment of Epilepsy.
AB  - Ketogenic diet (KD) therapy is an established form of treatment for both
      pediatric and adult patients with intractable epilepsy. Ketogenic diet is a term
      that refers to any diet therapy in which dietary composition would be expected to
      result in a ketogenic state of human metabolism. While historically considered a
      last-resort therapy, classic KDs and their modified counterparts, including the
      modified Atkins diet and low glycemic index treatment, are gaining ground for use
      across the spectrum of seizure disorders. Registered dietitian nutritionists are
      often the first line and the most influential team members when it comes to
      treating those on KD therapy. This paper offers registered dietitian
      nutritionists insight into the history of KD therapy, an overview of the various
      diets, and a brief review of the literature with regard to efficacy; provides
      basic guidelines for practical implementation and coordination of care across
      multiple health care and community settings; and describes the role of registered
      dietitian nutritionists in achieving successful KD therapy.

PMID- 28754199
TI  - Where Can I Find Nutrition Resources for Children and Adolescents Participating
      in Youth Sports?

PMID- 28754200
TI  - The Struggle Is Real: A Systematic Review of Food Insecurity on Postsecondary
      Education Campuses.
AB  - BACKGROUND: Numerous international studies have examined cross-sectional
      correlates of food insecurity (FI) among postsecondary education students.
      Research is needed to synthesize the findings of this work to support vulnerable
      students. OBJECTIVE: To systematically review peer-reviewed and gray literature
      to assess the prevalence of FI on postsecondary education institutions, as well
      as factors related to FI among students and suggested/practiced solutions.
      DESIGN: Systematic literature review. Medline, Web of Science, and PsycINFO
      databases were searched for peer-reviewed literature for FI research; a Google
      search (Google Inc) was conducted to obtain gray literature on FI among
      postsecondary education students. PARTICIPANTS/SETTING: Undergraduate and
      graduate students at postsecondary institutions of higher education. MAIN OUTCOME
      MEASURES: Measures included prevalence of FI; sociodemographic, health, and
      academic factors related to FI; and solutions to address FI on postsecondary
      institutions. RESULTS: Seventeen peer-reviewed studies and 41 sources of gray
      literature were identified (out of 11,476 titles). All studies were cross
      sectional. Rates of FI were high among students, with average rates across the
      gray and peer-reviewed literature of 35% and 42%, respectively. FI was
      consistently associated with financial independence, poor health, and adverse
      academic outcomes. Suggested solutions to address food security among
      postsecondary institutions addressed all areas of the socioecologic model, but
      the solutions most practiced included those in the intrapersonal, interpersonal,
      and institutional levels. CONCLUSIONS: FI is a major public health problem among
      postsecondary education students. Studies are needed to assess the long-term
      influence of FI among this vulnerable population. More research is needed on the
      effectiveness of FI interventions.

PMID- 28754201
TI  - Phenylketonuria Dietary Management and an Emerging Development.

PMID- 28754202
TI  - An improved strategy for stable biocontrol agents selecting to control rice
      sheath blight caused by Rhizoctonia solani.
AB  - Rice sheath blight caused by Rhizoctonia solani Kuhnis increasingly threatening
      rice production in China. DNA fingerprints of 220 R. solani strains isolated in
      11 provinces of China were established by random amplified polymorphic DNA (RAPD)
      PCR. Cluster analysis of strains isolated from the same region showed high
      similarity, indicating that the genetic diversity of R. solani strains is
      significantly related to geographical origin. We assessed potential bio-control
      abilities of bio-control agents (BCAs) by values according to inhibition zones
      against R. solani, extracellular hydrolytic enzymes activity and siderophores
      production in vitro. Fourteen strains with diverse expected bio-control potential
      were tested for their bio-control efficacy against rice sheath blight caused by
      11 pathogenic exemplars and for growth promoting ability, separately. Bio-control
      efficacy of single bacterium against various R. solani strains differed
      significantly (-36.23%~88.24%), while Pseudomonas fluorescens 4aYN11 achieved a
      relatively stable control efficacy of 32.26%-78.79% and growth promotion of
      18.43%. Pearson correlation coefficient between bio-control efficacy of each BCAs
      and their assessment is 0.717. In the present study, we established an improved
      strategy for screening stable bio-control agents based on an assessment system,
      their growth promotion potential and phylogenetic diversity of pathogen R.
      solani, and the result provides us not only one promising bio-control strain
      4aYN11 with an average bio-control efficacy of 56.50%, but also a practical way
      for future screen of novel BCAs.

PMID- 28754203
TI  - Arsenic inorganic compounds cause oxidative stress mediated by the transcription
      factor PHO4 in Candida albicans.
AB  - Arsenic is a toxic metalloid widespread in nature. Recently, it has been
      demonstrated a main role of the transcription factor Pho4 in the acquisition of
      tolerance to arsenic-derived compounds, arsenite and arsenate in Candida
      albicans. Here, the effect of these compounds on this pathogenic yeast has been
      analyzed. In wild type cells, both arsenite and arsenate induced a marked
      increase in the endogenous production of Reactive Oxygen Species (ROS), together
      with the accumulation of intracellular trehalose and the activation of catalase,
      suggesting their role as generators of oxidative stress in this yeast. However, a
      pho4 null mutant showed a minor increase of intracellular ROS and a different
      kinetics of catalase activation upon exposure to arsenite and arsenate.
      Interestingly, the enzymatic activity of glutathione reductase and superoxide
      dismutase were exclusively triggered by arsenite but not by arsenate. pho4 mutant
      cells were also found to be sensitive to azide but significantly resistant to
      arsenate through a process dependent on an active electron transport chain and
      the alternative oxidase system. Therefore, arsenic-derived compounds induce a
      strong antioxidant response in C.albicans via different mechanisms.

PMID- 28754204
TI  - Bacterial magnetosome and its potential application.
AB  - Bacterial magnetosome, synthetized by magnetosome-producing microorganisms
      including magnetotactic bacteria (MTB) and some non-magnetotactic bacteria (Non
      MTB), is a new type of material comprising magnetic nanocrystals surrounded by a
      phospholipid bilayer. Because of the special properties such as single magnetic
      domain, excellent biocompatibility and surface modification, bacterial
      magnetosome has become an increasingly attractive for researchers in biology,
      medicine, paleomagnetism, geology and environmental science. This review briefly
      describes the general feature of magnetosome-producing microorganisms. This
      article also highlights recent advances in the understanding of the biochemical
      and magnetic characteristics of bacterial magnetosome, as well as the magnetosome
      formation mechanism including iron ions uptake, magnetosome membrane formation,
      biomineralization and magnetosome chain assembly. Finally, this review presents
      the potential applications of bacterial magnetosome in biomedicine, wastewater
      treatment, and the significance of mineralization of magnetosome in biology and
      geology.

PMID- 28754205
TI  - The Galpha1-cAMP signaling pathway controls conidiation, development and
      secondary metabolism in the taxol-producing fungus Pestalotiopsis microspora.
AB  - G-protein-mediated signaling pathways regulate fungal morphogenesis, development
      and secondary metabolism. In this study, we report a gene, pgalpha1, that
      putatively encodes the alpha-subunit of a group I G protein in Pestalotiopsis
      microspora NK17, which is known to produce various secondary metabolites,
      including the antitumor drug taxol and pestalotiollide B (PB). Mutants of
      pgalpha1 showed retarded vegetative growth, aging of the mycelium, premature
      conidiation, deformed conidia, significantly increased melanin production, and a
      sharp decrease in PB production. The introduction of extra copies of pgalpha1 led
      to a different phenotype that was characterized by enhanced production of PB. qRT
      PCR revealed that the expression of pks1, which encodes melanin polyketide
      synthase, an enzyme that is involved in 1, 8-dihydroxynaphthalene (DHN) melanin
      biosynthesis, was up regulated by 55-fold in the absence of pgalpha1. Changes in
      conidiation and PB production in pgalpha1 mutants were able to be restored by the
      addition of exogenous cAMP. The deficiencies of PB production and conidiation in
      Deltapgalpha1 were not able to be rescued by deletion or overexpression of a
      previously reported histone deacetylase gene (hid1), suggesting that pgalpha1 is
      able to override the effect of hid1 on PB production and conidiation. Our results
      suggested that the G protein-cAMP pathway plays a critical role in vegetative
      growth as well as in asexual development of P. microspora.

PMID- 28754206
TI  - Improving gentamicin B and gentamicin C1a production by engineering the
      glycosyltransferases that transfer primary metabolites into secondary metabolites
      biosynthesis.
AB  - Gentamicin B and gentamicin C1a are the direct precursor for Isepamicin and
      Etimicin synthesis, respectively. Although producing strains have been improved
      for many years, both gentamicin B titer and gentamicin C1a titer in the
      fermentation are still low. Because all gentamicin components are biosynthesized
      using UDP-N-acetyl-d-glucosamine (UDP-GlcNAc) and UDP-xylose as precursors, we
      tried to explore strategies for development of strains capable of directing
      greater fluxes of these precursors into production of gentamicins. The
      glycosyltransferases KanM1 and GenM2, which are responsible for UDP-GlcNAc and
      UDP-xylose transfer, respectively, were overexpressed in gentamicin B producing
      strain Micromonospora echinospora JK4. It was found that gentamicin B could be
      improved by up to 54% with improvement of KanM1 and GenM2 expression during
      appropriately glucose feeding. To prove this strategy is widely usable, the KanM1
      and GenM2 were also overexpressed in gentamicin C1a producing strain, titers of
      gentamicin C1a improved by 45% when compared with titers of the starting strain.
      These results demonstrated overexpression the glycosyltransferases that transfer
      primary metabolites into secondary metabolites is workable for improvement of
      gentamicins production.

PMID- 28754207
TI  - Volatiles emitted by Bacillus sp. BCT9 act as growth modulating agents on Lactuca
      sativa seedlings.
AB  - Chemical products are applied during horticulture to increase food production,
      but the environmental problems resulting from these applications have led to a
      search for more sustainable products. Volatile organic compounds (VOCs)
      demonstrating plant growth promoter (PGP) activity released by bacterial species
      have emerged as alternatives, but their effects on Lactuca sativa growth are
      unknown. In this study, VOCs released by Bacillus sp. BCT9 cultures grown in
      different media (Methyl Red & Voges Proskauer, Murashige & Skoog and nutrient
      media) at concentrations of 0.1, 0.2, 0.5 and 0.7 (measured as the absorbance,
      lambda=600nm) were tested to evaluate their activity as growth inducers of L.
      sativa after 10days of exposure. Lower concentrations of BCT9 increased root
      length, and higher concentrations induced shoot length and lateral root length.
      The dry weight and number of lateral roots increased similarly, independent of
      concentration, for VOCs produced in all culture media. BCT9 cultures grown in
      Methyl Red & Voges Proskauer medium as bioactive compounds with or without
      lanolin. These VOCs increased shoot length, root length and dry weight at low
      concentrations, independent of the presence of lanolin. Lateral root length
      increased with the application of 2-nonanone (50ppm) and 2-undecanone (0.05ppm).
      Based on these results, the use of bioactive volatiles as growth inducers of
      horticultural species represents an alternative or complementary strategy.

PMID- 28754208
TI  - Involvement of Penicillium digitatum PdSUT1 in fungicide sensitivity and
      virulence during citrus fruit infection.
AB  - A putative sucrose transporter PdSUT1 included in the same clade that Sut1p from
      Schizosaccharomyces pombe was identified in Penicillium digitatum, the major
      citrus postharvest pathogen. PdSUT1 gene was characterized using target gene
      disruption and gene overexpression. The DeltaPdSUT1 mutants generated by gene
      elimination showed reduction in fungal virulence during citrus fruit infection
      assayed in mature fruit at 20 degrees C. However, the overexpression mutants did
      not increased disease severity neither in the mutants coming from a high virulent
      nor from a low virulent P. digitatum progenitor strains. Moreover, fungicide
      sensitivity was affected in the deletant mutants but not in the overexpression
      transformants. The expression analysis of several genes involved in fungicide
      resistance showed an intensification of MFS transporters and a decrease of sterol
      demethylases transcriptional abundance in the DeltaPdSUT1 mutants compare to the
      parental wild type strain. PdSUT1 appear not to be directly involved in fungicide
      resistance although can affect the gene expression of fungicide related genes.
      These results indicate that PdSUT1 contribute to P. digitatum fungal virulence
      and influence fungicide sensitivity through carbohydrate uptake and MFS
      transporters gene activation.

PMID- 28754209
TI  - Automated Volumetric Mammographic Breast Density Measurements May Underestimate
      Percent Breast Density for High-density Breasts.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate discrepancy
      in breast composition measurements obtained from mammograms using two
      commercially available software methods for systematic trends in overestimation
      or underestimation compared to magnetic resonance-derived measurements. MATERIALS
      AND METHODS: An institutional review board-approved, Health Insurance Portability
      and Accountability Act-compliant retrospective study was performed to calculate
      percent breast density (PBD) by quantifying fibroglandular volume and total
      breast volume derived from magnetic resonance imaging (MRI) segmentation and
      mammograms using two commercially available software programs (Volpara and
      Quantra). Consecutive screening MRI exams from a 6-month period with negative or
      benign findings were used. The most recent mammogram within 9 months was used to
      derive mean density values from "for processing" images at the per breast level.
      Bland-Altman statistical analyses were performed to determine the mean
      discrepancy and the limits of agreement. RESULTS: A total of 110 women with 220
      breasts met the study criteria. Overall, PBD was not different between MRI (mean
      10%, range 1%-41%) and Volpara (mean 10%, range 3%-29%); a small but significant
      difference was present in the discrepancy between MRI and Quantra (4.0%, 95% CI:
      2.9 to 5.0, P < 0.001). Discrepancy was highest at higher breast densities, with
      Volpara slightly underestimating and Quantra slightly overestimating PBD compared
      to MRI. The mean discrepancy for both Volpara and Quantra for total breast volume
      was not significantly different from MRI (p = 0.89, 0.35, respectively). Volpara
      tended to underestimate, whereas Quantra tended to overestimate fibroglandular
      volume, with the highest discrepancy at higher breast volumes. CONCLUSIONS: Both
      Volpara and Quantra tend to underestimate PBD, which is most pronounced at higher
      densities. PBD can be accurately measured using automated volumetric software
      programs, but values should not be used interchangeably between vendors.

PMID- 28754210
TI  - Now You See It, But Would You Later? Examining the Mechanisms of Satisfaction of
      Search in the Fatigued Radiologist.

PMID- 28754211
TI  - Survival of a cardiac arrested victim with hypothermia despite severely elevated
      serum potassium (9.0 mmol/L).

PMID- 28754212
TI  - Health promotion research in active duty army soldiers: The road to a fit and
      ready force.
AB  - BACKGROUND: In the last decade the Military Health System has changed its
      paradigm to focus on health promotion and disease prevention. PURPOSE: This paper
      reviews a decade of research exploring the effects of military life on
      nutritional status and bone health of Army soldiers. METHOD: Descriptive and
      experimental approaches have assessed occupational demands on soldiers in
      variable environments that require optimal nutrition status and physical health.
      DISCUSSION: The prevalence of overweight and obesity in the military has risen
      dramatically and the implications for health, readiness, productivity, and cost
      demands attention. The related nutritional deficits such as suboptimal vitamin D
      status likely contribute to musculoskeletal injuries which have a greater impact
      on the performance and readiness of soldiers than any other medical condition in
      peacetime or conflict. CONCLUSION: The greatest challenge in our system for
      health is optimizing the performance of all soldiers while minimizing health
      risks and long-term disability resulting from occupational hazards, particularly
      those inherent to war.

PMID- 28754213
TI  - A program evaluation of the Patient CaringTouch System: A pre- and
      postimplementation assessment.
AB  - BACKGROUND: The Patient CaringTouch System (PCTS) is an innovative, strategic and
      patient-centric framework developed by the Army Nurse Corps for nursing care
      delivery that is designed to reduce nursing care variation and improve patient
      and nurse outcomes. PURPOSE: This manuscript describes a program evaluation of
      the PCTS. METHODS: A pre and post design was used to describe changes in patient
      and nursing measures following PCTS implementation. DISCUSSION: Overall there was
      a good uptake of the PCTS; however, concurrent with initiation of the PCTS,
      declines in staffing levels and increases in patient acuity were noted.
      Medication administration error rates declined, but fall with injury rates
      increased. Pain reassessment following pain medication administration improved,
      as did several aspects of the nursing practice environment. Nurses' job
      dissatisfaction and intent to leave increased; however, potentially preventable
      losses decreased. CONCLUSIONS: The program evaluation results will be used to
      target areas for improvement so that the PCTS may be sustained.

PMID- 28754214
TI  - A systematic review and meta-analysis of the prevalence of Leishmania infection
      in blood donors.
AB  - BACKGROUND: The risk of transfusion transmitted leishmaniasis (TTL) from
      apparently healthy persons or asymptomatic individuals, should not be ignored.
      Lack of a comprehensive review, encouraged us to design a systematic review with
      meta-analysis approach to assess the prevalence of Leishmania infection in
      healthy blood donors. METHODS: For this purpose, 6 English databases (PubMed,
      Scopus, Web of Sciences, Science Direct, EMBASE and CINAHL) were browsed from
      January 1990 to July 2016. RESULTS: Due to significant heterogeneity, the random
      effects model was used (I2=98.04% and 94.68%, for serological and molecular
      methods, respectively). A total of 496 papers were found through searching in
      which 17,816 apparently healthy blood donors were examined for Leishmania
      infection. The weighted overall prevalence of Leishmania infection in this group
      was estimated 4% (95% CI=2-7) and 8.7% (95% CI=4.2-14.3) using serological and
      molecular methods, respectively. CONCLUSIONS: High serological prevalence does
      not justify widespread donor screening. Leukodepletion filters would
      substantially decrease the risk of TTL, hence they are potentially proposed in
      endemic areas specifically for high-risk recipients. To better enlighten the
      epidemiological aspects of Leishmania infection in blood donors, it is suggested
      to perform high-level stewardship and more precise studies with regard to
      involved risk factors.

PMID- 28754215
TI  - [Hot lung nodules on PET-CT].

PMID- 28754216
TI  - [A fortuitous femoral lesion].

PMID- 28754217
TI  - [Histoseminar on inflammatory bowel diseases (IBD): Pre-test].

PMID- 28754218
TI  - [Histoseminar on inflammatory bowel diseases (IBD): Pre-test answers].

PMID- 28754219
TI  - [Histoseminar on inflammatory bowel diseases (IBD): Case no 01].

PMID- 28754220
TI  - [Metastatic melanoma in placenta: A new case with PDL1 immunostaining].

PMID- 28754221
TI  - [Even a cholecystitis can surprise you].

PMID- 28754222
TI  - Outcomes of Clostridium difficile-infected patients managed in a common isolation
      unit compared with isolation in their bed of diagnosis.
AB  - Cohorting Clostridium difficile infection (CDI) patients is a strategy which has
      not been thoroughly evaluated. We compared clinical characteristics and outcomes
      of CDI patients treated in a common isolation unit (CIU) versus those treated in
      their bed of diagnosis. Patients treated in the CIU showed lower mortality rates
      and antibiotic usage; however, a higher recurrence rate was reported.

PMID- 28754223
TI  - Health care worker perspectives of their motivation to reduce health care
      associated infections.
AB  - BACKGROUND: Health care-associated infections (HAIs) are largely preventable, but
      are associated with considerable health care burden. Given the significant cost
      of HAIs, many health care institutions have implemented bundled interventions to
      reduce HAIs. These complex behavioral interventions require considerable effort;
      however, individual behaviors and motivations crucial to successful and sustained
      implementation have not been adequately assessed. We evaluated health care worker
      motivations to reduce HAIs. METHODS: This was a phenomenologic qualitative study
      of health care workers in different roles within a university hospital, recruited
      via a snowball strategy. Using constructs from the Consolidated Framework for
      Implementation Research model, face-to-face semi-structured interviews were used
      to explore perceptions of health care worker motivation to follow protocols on
      HAI prevention. RESULTS: Across all types of health care workers interviewed,
      patient safety and improvement in clinical outcomes were the major motivators to
      reducing HAIs. Other important motivators included collaborative environment that
      valued individual input, transparency and feedback at both organizational and
      individual levels, leadership involvement, and refresher trainings and workshops.
      We did not find policy, regulatory considerations, or financial penalties to be
      important motivators. CONCLUSIONS: Health care workers perceived patient safety
      and clinical outcomes as the primary motivators to reduce HAI. Leadership
      engagement and data-driven interventions with frequent performance feedback were
      also identified as important facilitators of HAI prevention.

PMID- 28754224
TI  - Residual atherosclerotic cardiovascular disease risk in statin-treated adults:
      The Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Residual atherosclerotic cardiovascular disease (ASCVD) risk in
      statin-treated US adults without known ASCVD is not well described. OBJECTIVE: To
      quantitate residual ASCVD risk and its predictors in statin-treated adults.
      METHODS: We studied 1014 statin-treated adults (53.3% female, mean 66.0 years)
      free of clinical ASCVD in the Multi-Ethnic Study of Atherosclerosis. We examined
      ASCVD event rates by National Lipid Association risk groups over 11-year follow
      up and the relation of standard risk factors, biomarkers, and subclinical
      atherosclerosis measures with residual ASCVD event risk. RESULTS: Overall, 5.3%
      of participants were at low, 12.2% at moderate, 60.3% at high, and 22.2% at very
      high baseline risk. Despite statin therapy, age- and race-standardized ASCVD
      rates per 1000 person-years for men and women were both 4.9 for low/moderate
      risk, 19.1 and 14.2 for high risk, and 35.6 and 26.7 for very high risk,
      respectively. Specific independent predictors of residual risk included current
      smoking, family history, diabetes, high-sensitivity C-reactive protein, low
      density lipoprotein particle number, carotid intimal medial thickness, and
      especially coronary artery calcium score. Those on moderate- or high-intensity
      statins at baseline (compared with low intensity) had 39% lower risks and those
      who increased statin intensity 62% lower ASCVD event risks (P < .01). CONCLUSION:
      Residual risk of ASCVD remains high despite statin treatment and is predicted by
      specific risk factors and subclinical atherosclerosis. These findings may be
      helpful for identifying those at highest risk needing more aggressive treatment.

PMID- 28754225
TI  - [Low dose propofol vs. lidocaine for relief of resistant post-extubation
      laryngospasm in the obstetric patient].
AB  - BACKGROUND: Post-extubation laryngospasm is a dangerous complication that should
      be managed promptly. Standard measures were described for its management. We
      aimed to compare the efficacy of propofol (0.5mg.kg-1) vs. lidocaine (1.5mg.kg-1)
      for treatment of resistant post-extubation laryngospasm in the obstetric
      patients, after failure of the standard measures. METHOD: This study was
      conducted over 2 years on all obstetric patients scheduled for cesarean delivery.
      Post-extubation laryngospasm was initially managed with a standard protocol
      (removal of offending stimulus, jaw thrust, positive pressure ventilation with
      100% oxygen). When this protocol failed, the tested drug was the second line
      (lidocaine in the first year and propofol in the second year). Lastly,
      succinylcholine was used when the tested drug failed. RESULTS: In lidocaine
      group, 5% of parturients developed post-extubation laryngospasm, 31.9% of them
      were successfully treated via standard protocol, and 68.1% required lidocaine
      treatment. 65.6% of patients treated with lidocaine responded successfully and
      34.4% required succinylcholine to relieve laryngospasm. In propofol group, 4.7%
      of parturients developed post-extubation laryngospasm, 30.1% of them were
      successfully treated via standard protocol, and 69.9% required propofol
      treatment. 82.8% of patients treated with propofol responded successfully and
      17.2% required succinylcholine to relieve laryngospasm. CONCLUSION: Small dose of
      propofol (0.5mg.kg-1) is marginally more effective than lidocaine (1.5mg.kg-1)
      for the treatment of resistant post-extubation laryngospasm in obstetric
      patients, after failure of standard measures and before the use of muscle
      relaxants.

PMID- 28754226
TI  - Febrile Seizures and Epilepsy: Association With Autism and Other
      Neurodevelopmental Disorders in the Child and Adolescent Twin Study in Sweden.
AB  - BACKGROUND: There is a recently well-documented association between childhood
      epilepsy and
      earlysymptomaticsyndromeselicitingneurodevelopmentalclinicalexaminations
      (ESSENCE) including autism spectrum disorder, but the relationship between
      febrile seizures and ESSENCE is less clear. METHODS: The Child and Adolescent
      Twin Study in Sweden (CATSS) is an ongoing population-based study targeting twins
      born in Sweden since July 1, 1992. Parents of 27,092 twins were interviewed using
      a validated DSM-IV-based interview for ESSENCE, in connection with the twins'
      ninth or twelfth birthday. Diagnoses of febrile seizures (n = 492) and epilepsy
      (n = 282) were based on data from the Swedish National Patient Register.
      Prevalence of ESSENCE in individuals with febrile seizures and epilepsy was
      compared with prevalence in the twin population without seizures. The association
      between febrile seizures and ESSENCE was considered before and after adjustment
      for epilepsy. Age of diagnosis of febrile seizures and epilepsy was considered as
      a possible correlate of ESSENCE in febrile seizures and epilepsy. RESULTS: The
      rate of ESSENCE in febrile seizures and epilepsy was significantly higher than in
      the total population without seizures (all P < 0.001). After adjusting for
      epilepsy, a significant association between febrile seizures and autism spectrum
      disorder, developmental coordination disorder, and intellectual disability
      remained. Earlier age of onset was associated with all ESSENCE except attention
      deficit/hyperactivity disorder in epilepsy but not with ESSENCE in febrile
      seizures. CONCLUSIONS: In a nationally representative sample of twins, there was
      an increased rate of ESSENCE in childhood epilepsy and in febrile seizures.
      Febrile seizures alone could occur as a marker for a broader ESSENCE phenotype.

PMID- 28754227
TI  - Needle tract seeding following core biopsies in retroperitoneal sarcoma.
AB  - BACKGROUND: Retroperitoneal tumours often require a preoperative core needle
      biopsy to establish a histological diagnosis. Literature is scarce regarding the
      risk of biopsies in retroperitoneal sarcomas, so the aim of this study is to
      identify the potential risks of core needle biopsies causing needle tract
      recurrences or local recurrences. METHOD: Patients who underwent resection of a
      primary retroperitoneal sarcoma between 1990 and 2014 were identified from a
      prospectively maintained database from two tertiary referral centres. Patient
      demographics, tumour characteristics and biopsy techniques were examined. The
      primary endpoint was needle tract recurrence and local intra-abdominal
      recurrence. RESULTS: 498 patients were included in the analysis. The most common
      histological subtypes were liposarcoma (66%) and leiomyosarcoma (18%). Of the 498
      patients that underwent resection, 255 patients were diagnosed with a
      preoperative biopsy. Five patients (2%) developed a biopsy site recurrence: 3
      patients with leiomyosarcomas and 2 patients with dedifferentiated liposarcomas.
      All biopsy site recurrences occurred after trans-abdominal biopsies and were not
      performed with a co-axial technique. There was no significant difference in local
      recurrence rate between the patients with or without a biopsy (=0.30) or for the
      biopsy route (trans-abdominal or trans-retroperitoneal (p = 0.72)). CONCLUSION:
      The risk of a needle tract metastasis after core needle biopsy for
      retroperitoneal sarcoma is very low but not zero. The safest method seems a trans
      retroperitoneal approach with a co-axial technique. Local recurrence rate is not
      altered after doing a core needle biopsy.

PMID- 28754228
TI  - Post-treatment surveillance of thyroid cancer.
AB  - An increased incidence of differentiated thyroid cancer (DTC) has resulted in an
      increased population of thyroid cancer survivors requiring ongoing disease
      surveillance. Our institution's risk-adapted surveillance strategy is based on a
      contemporary understanding of disease biology, guided by analysis of prognostic
      factors and balanced application of available surveillance modalities. The goal
      of this strategy is to detect recurrent disease early, identify patients who
      would benefit from further treatment and reduce over investigation of low-risk
      patients. This article describes our center's risk-stratified approach to the
      postoperative surveillance of patients with differentiated thyroid cancer with
      reference to the recent 2015 American Thyroid Association management guidelines.

PMID- 28754229
TI  - [Hypersensitivity reactions to beta-lactam antibiotics].
AB  - Allergy to beta-lactam antibiotics is a common condition and about 10% of
      patients report being allergic to penicillin. However, this diagnosis is largely
      overestimated. Two types of allergy should be distinguished and include immediate
      hypersensitivity that can lead to anaphylactic shock and delayed
      hypersensitivity, ranging from the most common maculopapular exanthema to severe
      bullous toxidermia or life-threatening DRESS. Allergy challenge with oriented
      skin tests according to the clinical features, supplemented with oral challenge
      in the absence of contraindication, will confirm or invalidate the diagnosis of
      beta-lactam allergy and will help to identify if necessary safe alternatives to
      beta-lactams.

PMID- 28754230
TI  - Tissue-engineered vascular grafts for congenital cardiac disease: Clinical
      experience and current status.
AB  - Congenital heart disease is a leading cause of death in the newborn period, and
      man-made grafts currently used for reconstruction are associated with multiple
      complications. Tissue engineering can provide an alternative source of vascular
      tissue in congenital cardiac surgery. Clinical trials have been successful
      overall, but the most frequent complication is graft stenosis. Recent studies in
      animal models have indicated the important role of the recipient's immune
      response in neotissue formation, and that modulating the immune response can
      reduce the incidence of stenosis.

PMID- 28754231
TI  - Editorial commentary: Cardiac amyloidosis-Reversing the mindset and the
      cardiomyopathy.

PMID- 28754232
TI  - Motor subtype changes in early Parkinson's disease.
AB  - INTRODUCTION: Distinct motor subtypes of Parkinson's disease (PD) have been
      described through both clinical observation and through data-driven approaches.
      However, the extent to which motor subtypes change during disease progression
      remains unknown. Our objective was to determine motor subtypes of PD using an
      unsupervised clustering methodology and evaluate subtype changes with disease
      duration. METHODS: The Parkinson's Progression Markers Initiative database of 423
      newly diagnosed PD patients was utilized to retrospectively identify unique motor
      subtypes through a data-driven, hierarchical correlational clustering approach.
      For each patient, we assigned a subtype to each motor assessment at each follow
      up visit (time points) and by using published criteria. We examined changes in PD
      subtype with disease duration using both qualitative and quantitative methods.
      RESULTS: Five distinct motor subtypes were identified based on the motor
      assessment items and these included: Tremor Dominant (TD), Axial Dominant,
      Appendicular Dominant, Rigidity Dominant, and Postural and Instability Gait
      Disorder Dominant. About half of the patients had consistent subtypes at all time
      points. Most patients met criteria for TD subtype soon after diagnosis. For
      patients with inconsistent subtypes, there was an overall trend to shift away
      from a TD phenotype with disease duration, as shown by chi-squared test, p <
      0.001, and linear regression analysis, p < 0.05. CONCLUSION: These results
      strongly suggest that classification of motor subtypes in PD can shift with
      increasing disease duration. Shifting subtypes is a factor that should be
      accounted for in clinical practice or in clinical trials.

PMID- 28754233
TI  - Development and validation of an alternative version of the Parkinson's Disease
      Cognitive Rating Scale (PD-CRS).
AB  - INTRODUCTION: The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a valid
      and reliable instrument to screen for and diagnose mild cognitive impairment in
      PD (PD-MCI) and to monitor potential outcomes in clinical trials. Although this
      scale shows adequate sensitivity to change in non-demented PD patients, an
      alternative form (AF) with proven reliability could minimize practice effects
      associated with repeated testing. METHODS: We selected PD-CRS/AF items following
      the criteria proposed in the original PD-CRS. We assessed a prospective sample of
      75 non-demented PD patients (normal cognition, n = 50; PD-MCI, n = 25) using both
      tools, administered on two consecutive days, in a randomized order. RESULTS: The
      PD-CRS/AF showed a high internal consistency (Cronbach's alpha = 0.80).
      Differences between total mean scores were not significant. Floor/ceiling effects
      were acceptable. The discriminative power for MCI was high for both tools (area
      under the curve 0.91; 95% CI, 0.84-0.98 for PD-CRS; 0.88, 95% CI, 0.80-0.96 for
      PD-CRS/AF). Receiver operating curve analysis showed the optimal cut-off point of
      the two versions to discriminate PD-MCI from PD-normal cognition was <=81 (PD-CRS
      = sensitivity 94%, specificity 73%; PD-CRS/AF = sensitivity 92%, specificity
      73%). CONCLUSIONS: Our results suggest that the PD-CRS/AF is a valid and reliable
      instrument to complement the original PD-CRS as an analogous tool for serial
      cognitive testing for PD patients in clinical practice and cognitive trials.

PMID- 28754234
TI  - Effectiveness of botulinum toxin A injection for the treatment of secondary
      axillary bromhidrosis.
AB  - Surgical removal of apocrine glands is a valid treatment option for axillary
      bromhidrosis. However, malodor may recur after the operation. The value of
      botulinum toxin A (BTX-A) injection in the treatment of secondary axillary
      bromhidrosis was investigated in the present study. From July of 2012 to May of
      2016, 53 patients with secondary axillary bromhidrosis were enrolled in our
      clinic. Various BTX-A injection strategies were applied depending on different
      types of previous surgery. None of the patients reported adverse side effects
      after the procedure. The duration of efficacy ranged from 1 to 12 months, with
      the median value of 6 months. At the end of follow-up, 48 patients ranked the
      satisfaction with BTX-A treatment as "very good" or "good". For patients with
      secondary axillary bromhidrosis following various surgical modalities, the BTX-A
      treatment strategy we propose can achieve a lengthy duration of efficacy with a
      low risk of side effects and should be considered a good and reliable option.

PMID- 28754235
TI  - Mechanical Thrombectomy for Acute Ischemic Stroke Patients Aged 80 Years or
      Older.
AB  - BACKGROUND: There are limited data about the prognostic factors predicting
      outcomes after mechanical thrombectomy with stent retrievers for the elderly.
      Here, we evaluated outcomes in elderly patients in a real-world setting. METHODS:
      Between April 2015 and January 2017, 80 patients with anterior intracranial acute
      large vessel occlusion, who had lived independently before ictus, were treated
      with mechanical thrombectomy using a stent retriever at our institute. We
      compared outcomes between patients >=80 years old (n = 36) and those <80 years
      old (n = 44), and assessed prognostic factors for favorable outcomes (modified
      Rankin Scale score 0-2) at 90 days in all patients. RESULTS: There was no
      significant difference in baseline National Institutes of Health Stroke Scale
      score and Alberta Stroke Program Early Computed Tomography Score between the 2
      groups. Successful revascularization (modified Thrombolysis in Cerebral
      Infarction [mTICI] scores 2b/3) (83% versus 93%, P = .286), complete
      recanalization (mTICI 3) (47% versus 50%, P = .826), and favorable outcomes (42%
      versus 57%, P = .261) were achieved more often in those <80 years old, but
      differences did not reach statistical significance. Multivariate regression
      analysis showed that baseline National Institutes of Health Stroke Scale (P =
      .013) and mTICI scores of 3 (P = .006) were significant predictive factors, but
      being >=80 years old and baseline Alberta Stroke Program Early Computed
      Tomography Score were not. In those >=80 years old, mTICI score of 3 was an
      influential factor for favorable outcome (P = .017). CONCLUSIONS: Being aged 80
      years or older was not a significant predictor for outcomes after mechanical
      thrombectomy, whereas complete recanalization was an influential predictor of
      outcome in the elderly.

PMID- 28754236
TI  - In reply to: "Hyperhidrosis caused by deep brain stimulation in the posterior
      subthalamic area" by Patric Blomstedt MD, PhD.

PMID- 28754237
TI  - Treatment of larva migrans syndrome with long-term administration of albendazole.
AB  - BACKGROUND: Larva migrans syndrome is a food-borne parasitic disease in humans,
      caused by accidental ingestion of eggs or larvae of ascarid nematodes, namely,
      Toxocara canis, Toxocara cati, or Ascaris suum, the roundworms commonly found in
      the intestines of dogs, cats and pigs respectively. When a patient is diagnosed
      as having larva migrans syndrome, oral-administration of albendazole is
      recommended, however, the regimen remains controversial worldwide. In Japan, the
      duration of albendazole administration is longer than those of European and North
      American countries. The purpose of this study was to assess the efficacy and
      safety of long-term administration treatment of albendazole for larva migrans
      syndrome. METHODS: From 2004 to 2014, our laboratory was involved in the
      diagnosis of 758 larva migrans syndrome cases, of which 299 cases could be
      followed up after the treatment. We analyzed these 299 follow-up cases on the
      ELISA results before and after the treatment as well as on anthelmintic used,
      dose and duration of medication, clinical findings, and side effects, recorded on
      a consultation sheet provided by the attending physicians. We have 288 cases as
      the subjects of this study. RESULTS: Albendazole represented a 78.0% efficacy
      rate. The side effects represented 15.0% in using albendazole alone cases;
      however, the side effects were mild to moderate and there were no severe cases
      reported. CONCLUSIONS: The long-term administration treatment of albendazole is
      safe and effective for larva migrans syndrome.

PMID- 28754238
TI  - Corrigendum to "Anti-ribosomal-P antibodies accelerate lupus glomerulonephritis
      and induce lupus nephritis in naive mice" [J. Autoimmun. 54C (2014) 118-126].

PMID- 28754239
TI  - Effectiveness of arthroscopically assisted surgery for ankle fractures: A meta
      analysis.
AB  - INTRODUCTION: This meta-analysis was performed to determine whether the
      arthroscopically assisted open reduction and internal fixation (ORIF) for ankle
      fractures is more beneficial than the conventional ORIF. METHODS: Articles in
      electronic medial databases were searched between March 1983 and August 2016,
      including Pubmed and SCOPUS. We included the studies with comparative design
      comparing the surgical outcomes between the arthroscopically assisted ORIF for
      ankle fractures and the conventional ORIF. Finally, two RCTs and two
      retrospective comparative studies were included for analysis. Mean and standard
      deviation (SD) of postoperative functional scores, number of subjects, and P
      values were extracted from the studies. In addition, postoperative follow-up
      period, fracture type, and study quality were collected. RESULTS: The pooled
      effect size of the four studies 0.535 (95% CI, 0.247-0.823) in Hedges's g, which
      favored the arthroscopically assisted ORIF over conventional ORIF. There was no
      evidence of publication bias in funnel plot and in Egger's test (p=0.534).
      CONCLUSION: The arthroscopically assisted ORIF for ankle fractures were more
      beneficial than the conventional ORIF in the current evidences. However, since it
      needs more medical cost and longer operation time, possible additional
      complications and cost effectiveness are to be validated in future studies.

PMID- 28754240
TI  - Resolution of the enigmatic phylogenetic relationship of the critically
      endangered Western Swamp Tortoise Pseudemydura umbrina (Pleurodira: Chelidae)
      using a complete mitochondrial genome.
AB  - Pseudemydura umbrina is one of the most endangered turtle species in the world,
      and the imperative for its conservation is its distinctive morphology and relict
      status among the Chelidae. We use Illumina sequencing to obtain the complete
      mitogenome for resolving its uncertain phylogenetic position. A novel nuclear
      paralogue confounded the assembly, and resolution of the authentic mitogenome
      required further Sanger sequencing. The P. umbrina mitogenome is 16,414bp
      comprising 37 genes organized in a conserved pattern for other vertebrates. The
      nuclear paralogue is 547bp, 97.8% identity to the corresponding mitochondrial
      sequence. Particular features of the mitogenome include an nd3 174+1A frameshift,
      loss of DHC loop in tRNASer (AGN), and a light-strand replication initiation site
      in Wancy region that extends into an adjacent tRNA gene. Phylogenetic analysis
      showed that P. umbrina is the monotypic sister lineage to the remaining
      Australasian Chelidae, a lineage probably dating back to the Cretaceous.

PMID- 28754241
TI  - Molecular phylogeny and timing of diversification in South American Cynolebiini
      seasonal killifishes.
AB  - The rich biological diversity of South America has motivated a series of studies
      associating evolution of endemic taxa with the dramatic geologic and climatic
      changes that occurred during the Cainozoic. The organism here studied is the
      killifish tribe Cynolebiini, a group of seasonal fishes uniquely inhabiting
      temporary pools formed during the rainy seasons. The Cynolebiini are found in
      open vegetation areas inserted in the main tropical and subtropical South
      American phytogeographical regions east of the Andes. Here, we present the first
      molecular phylogeny sampling all the eight genera of the Cynolebiini, using
      fragments of two mitochondrial and four nuclear genes for 35 species of
      Cynolebiini plus 19 species as outgroups. The dataset, 4448bp, was analysed under
      Bayesian and maximum likelihood approaches, providing a relatively well solved
      tree, which retrieves high support values for the Cynolebiini and most included
      clades. The resulting tree was used to estimate the time of divergence in
      included lineages using two cyprinodontiform fossils to calibrate the tree. We
      further investigated historical biogeography through the likelihood-based DEC
      model. Our estimates indicate that divergence between the clades comprising New
      World and Old World aplocheiloids occurred during the Eocene, about 50Mya, much
      more recent than the Gondwanan fragmentation scenario assumed in previous
      studies. This estimation is nearly synchronous to estimated splits involving
      other South American and African vertebrate clades, which have been explained by
      transoceanic dispersal through an ancient Atlantic island chain during the
      Palaeogene. We estimate that Cynolebiini split from its sister group
      Cynopoecilini in the Oligocene, about 25Mya and that Cynolebiini started to
      diversify giving origin to the present genera during the Miocene, about 20-14Mya.
      The Cynolebiini had an ancestral origin in the Atlantic Forest and probably were
      not present in the open vegetation formations of central and northeastern South
      America until the Middle Miocene, when expansion of dry open vegetation was
      favoured by cool temperatures and strike seasonality. Initial splitting between
      the genera Cynolebias and Simpsonichthys during the Miocene (about 14Mya) is
      attributed to the uplift of the Central Brazilian Plateau.

PMID- 28754242
TI  - REM sleep behavior disorder and obstructive sleep apnea: does one "evil" make the
      other less or more "evil"?

PMID- 28754243
TI  - In-situ atrazine biodegradation dynamics in wheat (Triticum) crops under variable
      hydrologic regime.
AB  - A comprehensive biodegradation reaction network of atrazine (ATZ) and its 18
      byproducts was coupled to the nitrogen cycle and integrated in a computational
      solver to assess the in-situ biodegradation effectiveness and leaching along a 5m
      deep soil cultivated with wheat in West Wyalong, New South Wales, Australia.
      Biodegradation removed 97.7% of 2kg/ha ATZ yearly applications in the root zone,
      but removal substantially decreased at increasing depths; dechlorination removed
      79% of ATZ in aerobic conditions and 18% in anaerobic conditions, whereas
      deethylation and oxidation removed only 0.11% and 0.15% of ATZ, respectively. The
      residual Cl mass fraction in ATZ and 4 byproducts was 2.4% of the applied mass.
      ATZ half-life ranged from 150 to 247days in the soil surface. ATZ reached 5m soil
      depth within 200years and its concentration increased from 1*10-6 to 4*10
      6mg/kgdry-soil over time. The correlation between ATZ specific biomass
      degradation affinity Phi0 and half-life t1/2, although relatively uncertain for
      both hydrolyzing and oxidizing bacteria, suggested that microorganisms with high
      Phi0 led to low ATZ t1/2. Greater ATZ applications were balanced by small
      nonlinear increments of ATZ biodegraded fraction within the root zone and
      therefore less ATZ leached into the shallow aquifer.

PMID- 28754244
TI  - 3D-printed biomaterials with regional auxetic properties.
AB  - Tissue engineering is replete with methods for inducing and mediating cell
      differentiation, which are crucial for ensuring proper regrowth of desired
      tissues. In this study, we developed a 3D-printed, non-positive Poisson's Ratio
      (NPPR) scaffold intended for future use in stretch-mediated cell differentiation
      applications, such as in muscle and tendon regeneration. We utilized dynamic
      optical projection stereolithography (DOPsL) to fabricate multi-layered, cell
      laden NPPR scaffolds - these scaffolds can not only support aggregate cell
      growth, but can also be printed with locally-tunable force-displacement
      properties at length scales appropriate for tissue interaction. These NPPR
      multilayered mesh scaffolds can be embedded into highly elastic hydrogels in
      order to couple a reduced NPPR behavior to a normally Positive Poisson's Ratio
      (PPR) solid bulk material. This hybrid structure may potentially enable induced
      'auxetic' behavior at the single-cell scale while tuning the Poisson's Ratio to a
      more isolated value. This would be uniquely suited for providing stretch-mediated
      effects for various cell-types within the tendon-to-muscle tissue transition.

PMID- 28754245
TI  - Iatrogenic Trochlear Chondral Defects After Anterolateral Placement of Retrograde
      Femoral Nails.
AB  - Femoral shaft fractures are common injuries with an incidence of 37.1 per 100,000
      person-years in the United States. Retrograde femoral nailing is an increasingly
      used treatment strategy to manage these injuries, particularly in fractures below
      stemmed hip prostheses, in supracondylar or distal femur fractures, in fractures
      in pregnant or obese patients, and when concomitant ipsilateral acetabular/pelvic
      ring fractures are present. Retrograde fixation has been shown to be a viable
      option with union rates comparable to antegrade intramedullary nailing. Despite
      having excellent results in the treatment of femoral fractures, retrograde
      femoral nails have been associated with iatrogenic patellofemoral chondral damage
      that may occur because of malpositioning of the intramedullary nail at the entry
      point. The objective of this case report is to describe 2 patients who suffered
      iatrogenic trochlear chondral defects after retrograde femoral nailing and
      subsequently underwent osteoarticular allograft transplantation surgery.

PMID- 28754246
TI  - A Contact Pressure Analysis Comparing an All-Inside and Inside-Out Surgical
      Repair Technique for Bucket-Handle Medial Meniscus Tears.
AB  - PURPOSE: To directly compare effectiveness of the inside-out and all-inside
      medial meniscal repair techniques in restoring native contact area and contact
      pressure across the medial tibial plateau at multiple knee flexion angles.
      METHODS: Twelve male, nonpaired (n = 12), fresh-frozen human cadaveric knees
      underwent a series of 5 consecutive states: (1) intact medial meniscus, (2) MCL
      tear and repair, (3) simulated bucket-handle longitudinal tear of the medial
      meniscus, (4) inside-out meniscal repair, and (5) all-inside meniscal repair.
      Knees were loaded with a 1,000-N axial compressive force at 5 knee flexion angles
      (0 degrees , 30 degrees , 45 degrees , 60 degrees , 90 degrees ), and contact
      area, mean contact pressure, and peak contact pressure were calculated using thin
      film pressure sensors. RESULTS: No significant differences were observed between
      the inside-out and all-inside repair techniques at any flexion angle for contact
      area, mean contact pressure, and peak contact pressure (all P > .791). Compared
      with the torn meniscus state, inside-out and all-inside repair techniques
      resulted in increased contact area at all flexion angles (all P < .005 and all P
      < .037, respectively), decreased mean contact pressure at all flexion angles (all
      P < .007 and all P < .001, respectively) except for 0 degrees  (P = .097 and P =
      .39, respectively), and decreased peak contact pressure at all flexion angles
      (all P < .001, all P < .001, respectively) except for 0 degrees  (P = .080 and P
      = .544, respectively). However, there were significant differences in contact
      area and peak contact pressure between the intact state and inside-out technique
      at angles >=45 degrees  (all P < .014 and all P < .032, respectively).
      Additionally, there were significant differences between the intact state and all
      inside technique in contact area at 60 degrees  and 90 degrees  and peak contact
      pressure at 90 degrees  (both P < .005 and P = .004, respectively). Median values
      of intact contact area, mean contact pressure, and peak contact pressure over the
      tested flexion angles ranged from 498 to 561 mm2, 786 to 997 N/mm2, and 1,990 to
      2,215 N/mm2, respectively. CONCLUSIONS: Contact area, mean contact pressure, and
      peak contact pressure were not significantly different between the all-inside and
      inside-out repair techniques at any tested flexion angle. Both techniques
      adequately restored native meniscus biomechanics near an intact level. CLINICAL
      RELEVANCE: An all-inside repair technique provided similar, native-state
      restoring contact mechanics compared with an inside-out repair technique for the
      treatment of displaced bucket-handle tears of the medial meniscus. Thus, both
      techniques may adequately decrease the likelihood of cartilage degeneration.

PMID- 28754247
TI  - Off-line coupling of new generation centrifugal partition chromatography device
      with preparative high pressure liquid chromatography-mass spectrometry triggering
      fraction collection applied to the recovery of secoiridoid glycosides from
      Centaurium erythraea Rafn. (Gentianaceae).
AB  - A purification sequence including a Gilson CPC 250 PRO device coupled to PrepHPLC
      hyphenated with a MS triggering fraction collector was applied to isolate
      secoiridoid glycosides from a complex methanolic extract of Centaurium erythraea.
      This species is widely used for ethnomedicinal purposes around the Mediterranean
      Sea. The solvent system ethyle acetate/ethanol/water 7.5/3/5 was determined using
      shake-flask method targeting swertiamarin, the major secoiridoid of the extract.
      Optimization of CPC experimental parameters enabled the injection of 4g of
      extract with a flow rate of 40mL/min at 3000rpm to provide a secoiridoid
      glycosides enriched fraction. 130mg of this latter was submitted to a second step
      of purification by preparative HPLC (gradient water/formic acid (19:1) (A) and
      methanol (B) as follows: 0min, 85% A; 8min, 60% A; 12min, 55% A; 35min, 55% A;
      40min, 10% A; 50min, 10% A; 52min, 85% A; 55min, 85% A) to give swertiamarin
      (36mg, yield 27.7%, purity 98.2%). Other secoiridoid glycosides (sweroside,
      gentiopicroside, secologanol, secoxyloganin) were also isolated in minor amounts.
      As these monoterpene derivatives are responsible for several biological
      activities, their quick recovery with high yield and purity may serve as a model
      for further scale-up and industrial development.

PMID- 28754248
TI  - In tube-solid phase microextraction-nano liquid chromatography: Application to
      the determination of intact and degraded polar triazines in waters and recovered
      struvite.
AB  - In-tube solid-phase microextraction (IT-SPME) coupled to miniaturized liquid
      chromatography (LC) techniques are attractive mainly due to the column efficiency
      improvement, sensitivity enhancement and reduction of solvent consumption. In
      addition, the nanomaterials based sorbents can play a key role in the improvement
      of the extraction efficiency taking into account their interesting physical and
      chemical properties. Thus, in this work the performance of IT-SPME coupled to
      nano LC (NanoLC) has been compared with the performance of IT-SPME coupled to
      capillary LC (CapLC) with similar configurations for the determination of polar
      triazines including their degradation products. In both cases, a DAD detector was
      used. Different extractive phases such as TRB-5, TRB-5/c-SWNTs, TRB-5/c-MWNTs
      capillary columns have been tested. The dimensions of the capillary columns were
      0.32mm id*40cm length and 0.1 or 0.075mm i.d.*15cm length for the couplings with
      CapLC and NanoLC, respectively. The processed volume was 4mL for CapLC and 0.5mL
      for NanoLC. The elution was carried out with ACN:H2O (30:70, v/v). IT-SPME-NanoLC
      has shown a higher performance than IT-SPME-CapLC for the target analytes
      demonstrating the enhancement of the extraction efficiency with the former
      configuration. A new phase TEOS-MTEOS-SiO2NPs has been also proposed for IT-SPME
      NanoLC, which improves the retention of polar compounds. Compared with previously
      published works, improved LODs were achieved (0.025-0.5MUgL-1). The practical
      application of the proposed procedure has been demonstrated for the analysis of
      water samples and recovered struvite samples from wastewater treatment plants.
      Therefore, the proposed procedure can be an alternative method for regulatory
      purposes.

PMID- 28754249
TI  - Distribution pattern of anthroponotic cutaneous leishmaniasis caused by
      Leishmania tropica in Western Afghanistan during 2013-2014.
AB  - Anthroponotic cutaneous leishmaniasis (ACL), caused by Leishmania tropica, is the
      main cause of cutaneous leishmaniasis (CL) in the Herat province, Western
      Afghanistan. We investigated the role of environmental factors on ACL
      distribution in Herat. Epidemiological data from 2457 patients were retrieved
      from the local WHO sub-office. Shapefile layers of districts, cities, villages,
      land cover, soil type and digital elevation model (DEM) of the Herat province
      were used to assess, by logistic regression modelling, the effects of land cover,
      soil types, elevation, and proximity to the Harirud river on the distribution of
      ACL. The key determinants of distribution were: (i) close proximity to the
      Harirud river, (ii) elevation between 700 and 1200m, (iii) intensive and
      intermittent irrigated cultivated land, and (iv) Haplocalcids with Torriorthents
      and Torrifluvents soil types. No ACL cases were found below 700m, and a few cases
      were present at >1200m in irrigated areas around the Harirud river. These
      findings suggest that moist soil and the humidity from irrigated areas found
      between 700 and 1200m provide suitable breeding sites of Phlebotomus sergenti,
      the main sandfly vector of L. tropica in Afghanistan. The effect of elevation
      also explains the predominance of ACL over ZCL in this region. The present study
      showed that distribution of ACL is strongly associated with environmental factors
      in West Afghanistan where the political and socio-economic conditions may also
      affect the epidemiology of CL.

PMID- 28754250
TI  - Molecular context of Schistosoma mansoni transmission in the molluscan
      environments: A mini-review.
AB  - Schistosoma mansoni, being transmitted by some freshwater Biomphalaria snails, is
      a major causative agent of human schistosomiasis. In the absence of effective
      vaccine and alternative drug designs to fight against the disease, and with the
      limitations of molluscicide application, developing more efficient strategies to
      interrupt the snail-mediated parasite transmission is being emphasized as
      potentially instrumental in the efforts toward schistosomiasis elimination,
      hence, necessitating thorough and comprehensive understanding of the fundamental
      mechanisms involved in the transmission process. Based on the current advances,
      this paper presents a concise exposition of the cellular, biochemical, genetic
      and immunological dynamics of the complex and statge-by-stage interactions
      between the parasite and its vector in their aquatic environment. It also
      highlights the possible crosstalk between the parasite's intracellular cyclic
      adenosine monophosphate (cAMP) and p38 mitogen-activated protein kinase (p38
      MAPK) during the intramolluscan stage. Undoubtedly, decades of intensive
      investigation have untangled many S. mansoni-B. glabrata complexities, yet many
      aspects of the parasite-vector cycle which can help define potential control
      clues await further elucidation.

PMID- 28754251
TI  - Mosquitocidal potential of silver nanoparticles synthesized using local isolates
      of Bacillus thuringiensis subsp. israelensis and their synergistic effect with a
      commercial strain of B. thuringiensis subsp. israelensis.
AB  - Control of larval stages of Aedes aegypti is considered an effective approach for
      preventing outbreaks of dengue fever. In this work, silver nanoparticles (Ag NPs)
      were synthesized using the supernatant and insecticidal proteins from local
      isolates of Bacillus thuringiensis subsp. israelensis (Bti). Mosquitocidal
      activity assays against A. aegypti larvae revealed that the highest toxicity was
      obtained from the Ag NPs synthesized using supernatant of Bti K55 and the
      inclusion proteins of Bti K46 with a lethal concentration 50 (LC50) of 0.001 and
      0.008MUg/mL, respectively. The synthesized nanoparticles were characterized using
      UV-vis absorption spectrophotometry, scanning electron microscopy (SEM), SEM
      coupled with energy dispersive X-ray spectroscopy, X-ray diffraction and Fourier
      transform infrared spectroscopy. The synergistic studies revealed that the Ag NPs
      synthesized using supernatant of Bti K55 were synergized with commercial Bti
      cells with a synergistic factor (SF) of 3.3 and 10.0 for LC50 and LC90,
      respectively. In addition, the Ag NPs synthesized using inclusion proteins of Bti
      K46 were synergized with commercial Bti cells with a SF of 1.6 and 4.2 for LC50
      and LC90, respectively. This study provided the first report of the synergistic
      effect between Bti and Ag NPs. Such a combination could represent an effective
      approach for the control of the dengue vector and possibly reducing the
      likelihood of increased insect resistance to chemical control.

PMID- 28754252
TI  - Detection of selected arboviral infections in patients with history of persistent
      fever in Pakistan.
AB  - Surveillance is a valuable tool for understanding prevailing and previously
      undiagnosed infections in a geographic area. We examined 480 archived serum
      samples from patients with history of persistent fever (>40 degrees C, 60-72h)
      who were referred to hospitals in Rawalpindi/Islamabad, Lahore, and Faisalabad
      districts for dengue antibody detection in 2014-15. Each sample was processed for
      detection of antigens and seroconversion, using real-time polymerase chain
      reaction and enzyme linked immunosorbent assay, respectively, against dengue
      haemorrhagic fever (DHF) virus serotypes 1-4, West Nile virus fever (WNVF),
      Crimean-Congo haemorrhagic fever (CCHF), and Chikungunya virus (CGV). The
      presence of antigens and antibodies to at least one of the studied viral
      haemorrhagic fevers (VHFs) was detected in 465 (96.8%, 95% CI: 94.9-98.1) and 442
      samples (92.1%, 95% CI: 89.3-94.2), respectively. No sera were found positive to
      CCHF. There was a significant association between gender and positivity to at
      least one of the VHFs (chi2=8.12, df=1, p<0.005). Except for DHF serotype 2 and 3
      (tautau=0.41), Goodman and Kruskal's Tau statistic revealed no significant
      association for occurrence of different viruses within the studied population
      (tautau=0-0.06). Cosinor analysis confirmed significant seasonality, with a
      higher number of cases of persistent fever in August through November, peaking in
      October. The study suggests circulation of multiple arthropod-borne viral
      infections and, in addition to DHF, ascertain the needs for screening patients
      for CGV and WNVF too. It also demonstrates the necessity of well-integrated
      disease surveillance in several geographic regions and at-risk populations in
      Pakistan to develop appropriate disease and vector control strategies.

PMID- 28754253
TI  - Morphology and small subunit rDNA-based phylogeny of a new Henneguya species,
      infecting the ornamental fish Corydoras leucomelas from the Peruvian Amazon.
AB  - A new species of Myxosporea, Henneguya loreotoensis n. sp. is described
      parasitizing the gill filaments from 17 of 35 specimens (48.5%) of Corydoras
      leucomelas (Siluriformes: Callichthyidae) caught in the Nanay River, near village
      Ninarumi, in the Loreto state, Peru. Mature spores were ellipsoidal in shape from
      the frontal view, measuring 36.2+/-0.1MUm (36.1-36.3) in total length, 14.3+/
      0.1MUm (14.2-14.4) in body length, 5.1+/-0.1MUm (4.9-5.3) in width and 21.9+/
      0.1MUm (21.8-22.0) in the caudal process. The two polar capsules were symmetrical
      and elongated, measuring 5.1+/-0.1MUm (4.9-5.3) in length and 2.4+/-0.2MUm (2.1
      2.7) in width, containing a polar filament with five coils arranged obliquely to
      the longitudinal axis. The sporoplasm was binucleate. Partial sequencing of the
      ssu-rDNA of H. loretoensis n. sp. resulted in a total of 1676 nucleotides, and
      this sequence did not match any of the myxozoan available in the GenBank. The
      phylogenetic analysis shows H. loretoensis n. sp. as a sister species of
      Henneguya paraensis, another amazonian myxozoan parasite of Cichla temensis
      (Perciformes: Cichlidae).

PMID- 28754254
TI  - Anti-proteolytic property and bonding durability of mussel adhesive protein
      modified dentin adhesive interface.
AB  - OBJECTIVES: To evaluate the effect of mussel adhesive protein (MAP) on
      collagenase activity, dentin collagen degradation and microtensile dentin bond
      strength (MUTBS). METHODS: Three groups were designed: 1. experimental group:
      treated with MAP; 2. positive control: treated with GM6001 (collagenase
      inhibitor); 3. negative control: treated with distilled water (DW). For
      collagenase activity, Clostridiopeptidase-A was added to each group (n=5), and
      collagenase activity was assessed by colorimetric assay. For dentin collagen
      degradation, thirty dentin slabs were allocated to the three above groups (n=10).
      Dentin collagen degradation was evaluated by measuring released hydroxyproline by
      colorimetric assay after being incubated in Clostridiopeptidase-A for 7 days. For
      microtensile bond strength, sixty human third molars with flat dentin surfaces
      were etched by phosphoric acid and then assigned to the three above groups
      (n=20). An etch-and-rinse adhesive system was applied to all three groups as
      stated in standard clinic protocol. The test of MUTBS was performed before and
      after thermocycling and collagenase challenge. RESULTS: The collagenase
      activities (nmol/min/mg) in the group of MAP was significantly less inactive
      compared to the group of GM6001 and DW (MAP<GM6000<DW, p<0.01). The
      hydroxyproline concentrations (MUg/mL) was significantly less in the group of MAP
      compared to the group of GM6001 and DW (MAP<GM6000<DW, p<0.01). While there was
      no significant difference in the immediate MUTBS (MPa) among three groups
      (p>0.06), the value of MUTBSs after thermocycling and collagenase challenge was
      significantly greater in the group of MAP and GM6001 compared to the group of DW
      (MAP, GM6000>DW, p<0.001). SIGNIFICANCE: MAP inhibits collagenase activity,
      prevents dentin collagen degradation, and delays the deterioration of the dentin
      bonding of composite restoration over time.

PMID- 28754255
TI  - Tailoring a NICU-Based Tobacco Treatment Program for Mothers Who Are Dependent on
      Opioids.
AB  - OBJECTIVE: To collect formative information to design a tailored tobacco
      treatment intervention for women with newborns treated or evaluated for neonatal
      abstinence syndrome and to explore current tobacco use behaviors and facilitators
      and barriers to smoking cessation. DESIGN: Qualitative descriptive study.
      SETTING: An academic medical center in the southern United States. PARTICIPANTS:
      Mothers (N = 11) of newborns who were treated or evaluated for neonatal
      abstinence syndrome at birth within the preceding 3 months. Women recruited were
      older than 18 years and reported opioid dependence and smoking during pregnancy.
      METHODS: Participants took part in semistructured individual interviews that
      lasted approximately 1 hour. Interviews were professionally transcribed and
      analyzed in MAXQDA using content analysis. RESULTS: Five themes emerged from the
      data: Strategizing to Reduce Risk, Desire to Quit Smoking in the Future, Holding
      on to Smoking While Working Through Recovery, Feeling Judged by Nurses, and
      Feeling Supported and Empowered by Nurses. Participants reported that they to
      reduce risk to their newborns by avoiding second- and thirdhand smoke exposure.
      Participants wanted to stop smoking but reported many barriers, including
      multiple life stressors compounded by their newborns' extended stays in the
      hospital. However, most participants described overall positive experiences and
      the support of health care providers. CONCLUSION: Holistic tobacco treatment
      programs that incorporate stress relief and social support and are led by trusted
      health care providers have the potential to be effective to reduce smoking in new
      mothers with histories of opioid dependence disorders and smoking and whose
      newborns are in the NICU.

PMID- 28754256
TI  - On the integral use of foundational concepts in verifying validity during skull
      photo superimposition.
AB  - Often cited reliability test on video superimposition method integrated scaling
      face-images in relation to skull-images, tragus-auditory meatus relationship in
      addition to exocanthion-Whitnall's tubercle relationship when orientating the
      skull-image and wipe mode imaging in addition to mix mode imaging when obtaining
      skull-face image overlay and evaluating the goodness of match. However, a report
      that found higher false positive matches in computer assisted superimposition
      method transited from the above foundational concepts and relied on images of
      unspecified sizes that are lesser than 'life-size', frontal plane landmarks in
      the skull- and face- images alone for orientating the skull-image and mix images
      alone for evaluating the goodness of match. Recently, arguing the use of 'life
      size' images as 'archaic', the authors who tested the reliability in the computer
      assisted superimposition method have denied any method transition. This article
      describes that the use of images of unspecified sizes at lesser than 'life-size'
      eliminates the only possibility to quantify parameters during superimposition
      which alone enables dynamic skull orientation when overlaying a skull-image with
      a face-image in an anatomically acceptable orientation. The dynamic skull
      orientation process mandatorily requires aligning the tragus in the 2D face-image
      with the auditory meatus in the 3D skull-image for anatomically orientating the
      skull-image in relation to the posture in the face-image, a step not mentioned by
      the authors describing the computer assisted superimposition method. Furthermore,
      mere reliance on mix type images during image overlay eliminates the possibility
      to assess the relationship between the leading edges of the skull- and face-image
      outlines as also specific area match among the corresponding craniofacial organs
      during superimposition. Indicating the possibility of increased false positive
      matches as a consequence of the above method transitions, the need for testing
      the reliability in the superimposition method adopting concepts that are
      considered safe is stressed.

PMID- 28754257
TI  - EJCB - Molecular basis of protein fates in the secretory and endocytic pathways,
      and beyond.

PMID- 28754258
TI  - Viral minority variants in the core promoter and precore region identified by
      deep sequencing are associated with response to peginterferon and adefovir in
      HBeAg negative chronic hepatitis B patients.
AB  - BACKGROUND AND AIM: Precore (PC) and basal core promoter (BCP) mutations are
      associated with responses to interferon-based treatment in HBeAg-positive chronic
      hepatitis B (CHB) patients. Here, we identify viral minority variants in these
      regions and assess association with response to peginterferon-alfa (Peg-IFN) and
      adefovir combination therapy. PATIENTS AND METHODS: Ultra-deep pyrosequencing
      analysis of the BCP and PC region was performed for 89 CHB patients (42 HBeAg
      positive; 47 HBeAg-negative), at baseline and during treatment. Specifically,
      associations of individual positions with the HBeAg-negative phenotype were
      studied, as well as the association of the most prevalent mutations with combined
      response in HBeAg-positive and -negative patients at week 72 (HBeAg negativity,
      HBV-DNA <2000 IU/mL and ALT normalization at 24 weeks of treatment-free follow
      up). RESULTS: The mutations most strongly correlated with the HBeAg-negative
      phenotype were at positions 1762/1764 and 1896/1899 in the BCP and PC region,
      respectively. No major changes in nucleotide composition of these positions were
      observed during treatment. In HBeAg-negative patients, a combined presence of
      1764A and 1896A was correlated with lower ALT levels (p = 0.004), whereas the
      presence of 1899A was correlated with higher age (p = 0.030), lower HBV-DNA level
      (p = 0.036), and previous IFN therapy (p = 0.032). The presence of 1764A/1896A or
      the absence of 1899A at baseline, was associated with lower response rates, after
      adjustment for HBV genotype (p = 0.031 and p = 0.017) and HBsAg level (p = 0.035
      and p = 0.022). CONCLUSION: We identified novel correlations between common BCP
      and PC variants with response to Peg-IFN and adefovir in HBeAg-negative patients.
      Ultimately, this may guide the selection of those patients most likely to benefit
      from Peg-IFN-based treatment.

PMID- 28754259
TI  - Inflammation regulates 11beta-hydroxysteroid dehydrogenase type 1 differentially
      in specific compartments of the gut mucosal immune system.
AB  - The bioavailability of glucocorticoids is modulated by enzyme 11beta
      hydroxysteroid dehydrogenase type 1 (11HSD1), which catalyzes the conversion of
      inactive 11-oxo-glucocorticoids to active 11-hydroxy-glucocorticoids cortisol and
      corticosterone and is regulated by pro-inflammatory cytokines. Our aim was to
      assess the effect of colitis on the expression of 11HSD1 in specific
      microanatomical compartments of the mucosal immune system. Using qRT-PCR we
      quantified the expression of 11HSD1 and cytokines in the colon, mesenteric lymph
      nodes (MLN) and spleen of mice with colitis. Microsamples of the MLN cortex,
      paracortex and medulla, colonic crypt epithelium (CCE), lamina propria and
      isolated intestinal lymphoid follicles (ILF) were harvested by laser
      microdissection, whereas splenic and MLN lymphocytes by flow cytometry. Colitis
      increased 11HSD1 in the CCE, ILF, and MLN cortex but not in the lamina propria
      and the MLN paracortex and medulla. Expression of IL-4, IL-21 and TNFalpha was
      increased in both the cortex of MLN and ILF, whereas IL-1beta and IL-10 were only
      increased in the follicles. No positive effect was observed in the case of
      IFNgamma and TGFbeta. 11HSD1 was positively correlated with TNFalpha and less
      strongly with IL-21, IL-1beta, and IL-4. Colitis also upregulated the 11HSD1
      expression of T cells in the spleen and MLN. The study demonstrates the
      stimulatory effect of inflammation on local glucocorticoid metabolism only in
      particular compartments of the mucosal immune system. The correlation between
      cytokines and 11HSD1 in the ILF and MLN cortex indicates that pro-inflammatory
      cytokines may amplify glucocorticoid signals in inductive compartments of the
      mucosal immune system.

PMID- 28754260
TI  - Learning curve of tonsillectomy.
AB  - OBJECTIVE: To determine the time required to sufficiently educate a well-trained
      surgeon to perform tonsillectomy. MATERIAL AND METHODS: From July 1, 2000 to June
      30, 2008, we analyzed 110 patients who underwent bilateral tonsillectomy. All the
      procedures were performed by 16 ENT surgeons trained in the same tertiary
      referral medical center during their residency. This training included a 4-year
      training program before 2002, and a 5-year training program thereafter. We
      stratified the patients into groups according to each surgeon's residency year at
      the time the operations were performed. Operation time, estimated blood loss and
      length of hospital stay of these patients were compared by the surgeon's
      residency year and by different training program of residency. RESULTS: There was
      a trend of decreased operation time in the senior year of residency, especially
      for 5th year surgeons, without reaching statistical significance. When comparing
      different training program, the operation time was statistically shorter in the 5
      year training program than in the 4-year training program. However, no difference
      was noted in estimated blood loss and hospital stay length. CONCLUSION: The
      operation time of residents in the 5-year training program was shorter than that
      of residents in the 4-year training program, which implies that extending the
      training program by one year may improve the quality of training.

PMID- 28754261
TI  - Elucidating the weak protein-protein interaction mechanisms behind the liquid
      liquid phase separation of a mAb solution by different types of additives.
AB  - Liquid-liquid phase separation (LLPS) has long been observed during the physical
      stability investigation of therapeutic protein formulations. The buffer
      conditions and the presence of various excipients are thought to play important
      roles in the formulation development of monoclonal antibodies (mAbs). In this
      study, the effects of several small-molecule excipients (histidine, alanine,
      glycine, sodium phosphate, sodium chloride, sorbitol and sucrose) with diverse
      physical-chemical properties on LLPS of a model IgG1 (JM2) solutions were
      investigated by multiple techniques, including UV-vis spectroscopy, circular
      dichroism, differential scanning calorimetry/fluorimetry, size exclusion
      chromatography and dynamic light scattering. The LLPS of JM2 was confirmed to be
      a thermodynamic equilibrium process with no structural changes or irreversible
      aggregation of proteins. Phase diagrams of various JM2 formulations were
      constructed, suggesting that the phase behavior of JM2 was dependent on the
      solution pH, ionic strength and the presence of other excipients such as glycine,
      alanine, sorbitol and sucrose. Furthermore, we demonstrated that for this mAb,
      the interaction parameter (kD) determined at low protein concentration appeared
      to be a good predictor for the occurrence of LLPS at high concentration.

PMID- 28754262
TI  - A comparison of three Peyer's patch "M-like" cell culture models: particle
      uptake, bacterial interaction, and epithelial histology.
AB  - Intestinal Peyer's patch (PP) microfold (M) cells transport microbes and
      particulates across the follicle-associated epithelium (FAE) as part of the
      mucosal immune surveillance system. In vitro human M-like cell co-culture models
      are used as screens to investigate uptake of antigens-in-nanoparticles, but the
      models are labour-intensive and there is inter-laboratory variability. We
      compared the three most established filter-grown Caco-2/Raji B cell co-culture
      systems. These were Model A (Kerneis et al., 1997), Model B (Gullberg et al.,
      2000), and Model C (Des Rieux et al. 2007). The criteria used were
      transepithelial resistance (TEER), the apparent permeability coefficient (Papp)
      of [14C]-mannitol, M cell-like histology, as well as latex particle and
      Salmonella typhimurium translocation. Each co-culture model displayed substantial
      increases in particle translocation. Truncated microvilli compared to mono
      cultures was their most consistent feature. The inverted model developed by des
      Rieux et al. (2007) displayed reductions in TEER and an increased (Papp),
      accompanied by the largest increase in particle translocation compared to the
      other two models. The normally-oriented model developed by Gullberg et al. (2000)
      was the only one to consistently display an increased translocation of Salmonella
      typhimurium. By applying a double MatrigelTM coating on filters, altering the
      medium feeding regime for Raji B cells, and restricting the passage number of B
      cells, improvements to the Gullberg model B were achieved, as reflected by
      increased particle translocation and improved histology. In conclusion, this is
      the first time all three designs have been compared in one study and each
      displays phenotypic features of M-like cells. While Model C was the most robust
      co-culture, the Model B protocol could be improved by optimizing several
      variables and is less complicated to establish than the two inverted models.

PMID- 28754263
TI  - Clinical inertia and its impact on treatment intensification in people with type
      2 diabetes mellitus.
AB  - Many people with type 2 diabetes mellitus (T2DM) fail to achieve glycaemic
      control promptly after diagnosis and do not receive timely treatment
      intensification. This may be in part due to 'clinical inertia', defined as the
      failure of healthcare providers to initiate or intensify therapy when indicated.
      Physician-, patient- and healthcare-system-related factors all contribute to
      clinical inertia. However, decisions that appear to be clinical inertia may, in
      fact, be only 'apparent' clinical inertia and may reflect good clinical practice
      on behalf of the physician for a specific patient. Delay in treatment
      intensification can happen at all stages of treatment for people with T2DM,
      including prescription of lifestyle changes after diagnosis, introduction of
      pharmacological therapy, use of combination therapy where needed and initiation
      of insulin. Clinical inertia may contribute to people with T2DM living with
      suboptimal glycaemic control for many years, with dramatic consequences for the
      patient in terms of quality of life, morbidity and mortality, and for public
      health because of the huge costs associated with uncontrolled T2DM. Because
      multiple factors can lead to clinical inertia, potential solutions most likely
      require a combination of approaches involving fundamental changes in medical
      care. These could include the adoption of a person-centred model of care to
      account for the complex considerations influencing treatment decisions by
      patients and physicians. Better patient education about the progressive nature of
      T2DM and the risks inherent in long-term poor glycaemic control may also
      reinforce the need for regular treatment reviews, with intensification when
      required.

PMID- 28754264
TI  - Surgical management of posterior knee dislocation associated with extensor
      apparatus rupture.
AB  - OBJECTIVE: The purpose of this study was to report the clinical and functional
      results of patients who underwent surgical management for posterior knee
      dislocation associated with extensor apparatus rupture. INTRODUCTION: Posterior
      knee dislocations associated with extensor apparatus ruptures are defined as rare
      but complicated injuries, which are difficult to return to the level of activity
      prior to the injury. The study demonstrated a hypothesis that good knee stability
      and early gain of range of motion could be achieved with deliberate design of the
      treatment protocol and proper application of the instruments. METHODS: Fifteen
      patients with posterior knee dislocations associated with extensor apparatus
      ruptures were evaluated after reduction and repair of extensor apparatus.
      Following that, multiple-ligament reconstruction in association with use of a
      lateral knee-spanning external fixator was applied for at least six weeks.
      Ligament reconstructions were performed using allografts. Range of motion and
      knee stability were both measured at each follow-up evaluation at a mean time of
      36months. The assessment was made using the Lysholm Knee Scoring Scale. RESULTS:
      The mean Lysholm scale score was 87.6 (range 73-95), with excellent in 11 cases,
      good in two, and fair in two. In the final evaluation, the range of motion was a
      mean range of 123.4 degrees  (range 100-135). CONCLUSION: The use of a lateral
      knee-spanning external fixator ensured the safety of repaired vessels, knee
      stability after reduction, and early rehabilitation with range of motion.

PMID- 28754265
TI  - Evaluation of prevalence, immunogenicity and efficacy of FyuA iron receptor in
      uropathogenic Escherichia coli isolates as a vaccine target against urinary tract
      infection.
AB  - Uropathogenic Escherichia coli (UPEC) are among the most prevalent agents of
      urinary tract infections (UTIs). Antibiotic resistance reaches the need for
      alternative treatment approaches such as vaccination against UTIs. There is no
      ideal vaccine against UTIs, thus there is a need to evaluate different targets of
      uropathogens against UTIs. Ferric scavenger receptor FyuA in UPEC has the
      properties of an ideal vaccine candidate against UTIs. In the present study, the
      prevalence of FyuA among UPEC isolates, its immunogenicity with and without alum
      adjuvant, and its efficacy against experimental UTI were assessed. Totally, fyuA
      gene was present in 77% of the UPEC isolates tested. Alignments of FyuA exhibited
      a high degree of conservation among different submitted UPEC isolates in GenBank.
      The bioinformatics studies showed the high confidence value and stability of the
      FyuA structure. SDS-PAGE and Western blot confirmed the purification of FyuA with
      high yield by nickel resins. Mice vaccinated subcutaneously with the FyuA induced
      a significantly higher humoral response (total IgG, IgG1 and IgG2a) than control
      mice that alum enhanced these responses. The FuyA alone showed the ability to
      reduce the colonization of UPEC in bladder and kidney of mice as compared to the
      control group. But the addition of alum to FyuA increased the protection level
      against UPEC in these organs. Since, FyuA induced significant IgG1 (Th2) and
      IgG2a (Th1) responses and protected the mice against experimental UTI, it could
      be a promising target against UPEC infections.

PMID- 28754266
TI  - Detection of anti-Leptospira inhibitory antibodies in horses after vaccination.
AB  - Leptospirosis is a relevant zoonosis that affects the reproductive performance of
      livestock, impairing the economy. Few studies have demonstrated the effects of
      vaccination against leptospirosis on naturally exposed horses. This study aimed
      to detect anti-Leptospira inhibitory antibodies in horses after vaccination. A
      total of 54 mares were studied using Growth Inhibition Test (GIT) in three
      moments. The present results demonstrate the usefulness of GIT for confirming
      inhibitory effects of specific antibody production. Results have also
      demonstrated that vaccination positively influenced on the presence of inhibitory
      antibodies in horses.

PMID- 28754267
TI  - Efficient production and optimization of E7 oncoprotein from Iranian human
      papillomavirus type 16 in Lactococcus lactis using nisin-controlled gene
      expression (NICE) system.
AB  - The present work was aimed at investigating the expression and optimization of a
      human papillomavirus (HPV) type 16 gene encoding oncoprotein E7 in Lactococcus
      lactis. We genetically engineered Lactococcus lactis using nisin-controlled gene
      expression (NICE) system pNZ8148 to express the native and codon optimized E7
      oncogenes isolated from Iranian HPV-16. The results of optimizing fermentation
      showed, the concentration of produced protein was expressively improved by 10
      ng/mL nisin after 3.5, and 4 h induction for NZ9000 harboring the codon
      optimized, and native E7 respectively. Furthermore the recombinant NZ9000 strains
      expressed rE7 by maximum value of 4.7 (Codon-optimized), and 1.82 MUg/mL (Native)
      in static flask experiments at initial glucose concentrations of 50 and 75 g/L
      respectively. The rE7 yield was further enriched in batch fermenter experiments
      using controlled pH. Thus, the overall production of rE7 under optimized
      conditions accumulated in the cytoplasm to nearly 33.25 MUg/mL by L. lactis
      NZ9000 containing codon-optimized E7, which was over ~2.7-fold higher compared to
      the NZ9000 having native E7 strain (12.01 MUg/mL). Accordingly, the maximum
      biomass production was calculated 4.87, and 1.51 g/L respectively.

PMID- 28754268
TI  - Cannabinoid system of dorsomedial telencephalon modulates behavioral responses to
      noxious stimulation in the fish Leporinus macrocephalus.
AB  - Fish dorsomedial telencephalon has been considered a pallial region homologous to
      mammals amygdala, being considered a possible substrate for nociception
      modulation in this animal group. The present study aimed to evaluate the
      participation of the cannabinoid system of Dm telencephalon on nociception
      modulation in the fish Leporinus macrocephalus. We demonstrated that cannabidiol
      microinjection in Dm telecephalon inhibits the behavioral nociceptive response to
      the subcutaneous injection of 3% formaldehyde, and this antinociception is
      blocked by previous treatment with AM251 microinjection. Furthermore, AM251
      microinjection in Dm prior to restraint stress also blockades the stress-induced
      antinociception. These results reinforce the hypothesis that this pallial
      telencephalic structure has a pivotal role in nociception modulation in fish.

PMID- 28754269
TI  - Cholangiohepatitis With Extensive Intrahepatic Choledocholithiasis.

PMID- 28754270
TI  - Fast acceleration of ASL-based time-resolved magnetic resonance angiography by
      acquisition of control and labeled images in the same shot (fast ACTRESS): An
      optimization study.
AB  - PURPOSE: To establish an optimized sequence design for fast acceleration of
      arterial spin labeling (ASL)-based time-resolved magnetic resonance angiography
      (MRA) by acquisition of control and labeled images in the same shot (fast
      ACTRESS) and a scan time of <1min, for the evaluation of intracranial vessels.
      MATERIALS AND METHODS: Ten healthy volunteers with no unilateral symptomatic
      arterial stenosis, who underwent 3-tesla MRI, were investigated. Imaging
      parameters for the fast ACTRESS sequence were set with an acquisition time of
      45s. During post-processing, the first phase in the multi-phase readout, which
      was defined as the control image, was subtracted from each of the other phases.
      Thus, four-dimensional (4D)-MRA images of each phase were obtained. The maximum
      intensity projection was used for the reconstruction of 4D-MRA images and time-to
      signal intensity curves (TIC) obtained for each vessel. The area under the curve
      (AUC), peak time, and maximum signal intensity were obtained from TIC. The
      different labeling types were broadly divided into six groups: L1, L2, L3, L4,
      L5, and L6 according to the actual number of labeling pulse. RESULTS: A total of
      5040 regions of interest were evaluated. The peak SI of L3, except for those in
      the A2 segment of the anterior cerebral artery, was significantly higher than
      that of L5. However, there were no significant differences between L4 and L5.
      Although the AUCs of L3 and L4 for anterior circulation were relatively higher
      than that of the other subgroups, the AUC of L3 was significantly higher than
      that of L4. CONCLUSION: The fast ACTRESS was optimized and indicated that the
      labeling type of L3 was the most appropriate for the well visualization of
      intracranial arteries. The fast ACTRESS sequence was useful to acquire well
      delineated images of intracranial vessels in ?1min.

PMID- 28754272
TI  - Correction to Lancet Haematol 2017; 4: e362-73.

PMID- 28754271
TI  - Afferent cardiac signals modulate attentional engagement to low spatial frequency
      fearful faces.
AB  - Despite the growing consensus that the continuous dynamic cortical
      representations of internal bodily states shape the subjective experience of
      emotions, physiological arousal is typically considered only a consequence and
      rarely a determinant of the emotional experience. Recent experimental approaches
      study how afferent autonomic signals from the heart modulate the processing of
      sensory information by focussing on the phasic properties of arterial
      baroreceptor firing that is active during cardiac systole and quiescent during
      cardiac diastole. For example, baroreceptor activation has been shown to enhance
      the processing of threat-signalling stimuli. Here, we investigate the role of
      cardiac afferent signals in the rapid engagement and disengagement of attention
      to fear stimuli. In an adapted version of the emotional attentional cueing
      paradigm, we timed the presentation of cues, either fearful or neutral faces, to
      coincide with the different phases of the cardiac cycle. Moreover, we presented
      cues with different spatial frequency ranges to investigate how these
      interoceptive signals influence the processing of visual information. Results
      revealed a selective enhancement of attentional engagement to low spatial
      frequency fearful faces presented during cardiac systole relative to diastole. No
      cardiac cycle effects were observed to high spatial frequency nor broad spatial
      frequency cues. These findings expand our mechanistic understanding of how body
      brain interactions may impact the visual processing of fearful stimuli and
      contribute to the increased attentional capture of threat signals.

PMID- 28754273
TI  - Effects of psychopharmacological treatment with antidepressants on the vascular
      system.
AB  - Psychopharmacological treatment with antidepressants is an essential part of
      guideline-based treatment strategies in affective disorders, such as major
      depressive disorder, persistent depressive disorder, and bipolar disorder.
      Furthermore, antidepressants are frequently prescribed in patients with physical
      disorders, such as cardiovascular diseases, and comorbid depression. The type of
      association between physical diseases, particularly chronic diseases, and
      depression is bidirectional, meaning that affective disorders enhance the risk
      for the development of cardiovascular and metabolic disorders, and that
      cardiovascular/metabolic disorders enhance the risk for the development of
      depressive disorders. Therefore, knowledge of vascular side effects of
      psychopharmacological treatment is important for clinicians. This clinical
      orientated review article covers direct and indirect effects of commonly
      prescribed antidepressant drugs on the vascular system.

PMID- 28754274
TI  - Review: Structure, function and evolution of GnIH.
AB  - Neuropeptides that possess the Arg-Phe-NH2 motif at their C-termini (i.e.,
      RFamide peptides) have been characterized in the nervous system of both
      invertebrates and vertebrates. In vertebrates, RFamide peptides make a family and
      consist of the groups of gonadotropin-inhibitory hormone (GnIH), neuropeptide FF
      (NPFF), prolactin-releasing peptide (PrRP), kisspeptin (kiss1 and kiss2), and
      pyroglutamylated RFamide peptide/26RFamide peptide (QRFP/26RFa). It now appears
      that these vertebrate RFamide peptides exert important neuroendocrine,
      behavioral, sensory, and autonomic functions. In 2000, GnIH was discovered as a
      novel hypothalamic RFamide peptide inhibiting gonadotropin release in quail.
      Subsequent studies have demonstrated that GnIH acts on the brain and pituitary to
      modulate reproductive physiology and behavior across vertebrates. To clarify the
      origin and evolution of GnIH, the existence of GnIH was investigated in
      agnathans, the most ancient lineage of vertebrates, and basal chordates, such as
      tunicates and cephalochordates (represented by amphioxus). This review first
      summarizes the structure and function of GnIH and other RFamide peptides, in
      particular NPFF having a similar C-terminal structure of GnIH, in vertebrates.
      Then, this review describes the evolutionary origin of GnIH based on the studies
      in agnathans and basal chordates.

PMID- 28754275
TI  - Retraction notice to "Design of a Phase 3, Double-Blind, Randomized Trial of
      Lomitapide vs. Placebo in Pediatric Patients with Homozygous Familial
      Hypercholesterolemia" J Clin Lipidol 9 (2015) 447.

PMID- 28754276
TI  - Physiological correlates of emotional reactivity and regulation in early
      adolescents.
AB  - Few studies have examined physiological correlates of emotional reactivity and
      regulation in adolescents, despite the occurrence in this group of significant
      developmental changes in emotional functioning. The current study employed
      multiple physiological measures (i.e., startle-elicited eyeblink and ERP, skin
      conductance, facial EMG) to assess the emotional reactivity and regulation of 113
      early adolescents in response to valenced images. Reactivity was measured while
      participants viewed images, and regulation was measured when they were asked to
      discontinue or maintain their emotional reactions to the images. Adolescent
      participants did not exhibit fear-potentiated startle blink. However, they did
      display affect-consistent zygomatic and corrugator activity during reactivity, as
      well as inhibition of some of these facial patterns during regulation. Skin
      conductance demonstrated arousal dependent activity during reactivity, and
      overall decreases during regulation. These findings suggest that early
      adolescents display reactivity to valenced pictures, but not to startle probes.
      Psychophysiological patterns during emotion regulation indicate additional effort
      and/or attention during the regulation process.

PMID- 28754277
TI  - Deficient prepulse inhibition of the startle reflex in schizophrenia using a
      cross-modal paradigm.
AB  - OBJECTIVES: To investigate whether the typically reported deficient sensorimotor
      gating in patients with schizophrenia using unimodal paradigms can also be
      detected by a cross-modal paradigm which made use of an electrocutaneous-acoustic
      coupling of stimuli. METHODS: Twenty-one male schizophrenia patients took part in
      a prepulse inhibition (PPI) paradigm with an electrocutaneous prepulse and an
      acoustic startle-eliciting pulse. Their results were compared with those from
      nineteen healthy males. RESULTS: As expected, the patients showed significantly
      lower PPI than controls. No associations were found between measures of illness
      severity and PPI. DISCUSSION: To the best of our knowledge, this is the first
      study showing reduced PPI in patients with schizophrenia by using an
      electrocutaneous-acoustic prepulse-pulse combination. Hence, this study gives
      further evidence of a modality-independent sensorimotor gating deficit in
      schizophrenia. Furthermore, as PPI was also lower than usual in controls using
      unimodal paradigms, results are interpreted in favour of longer processing times
      of the electrocutaneous prepulse, which probably led to a shorter perceived
      stimulus onset asynchrony (SOA) in the brain.

PMID- 28754278
TI  - [Effects of deformational plagiocephaly during the first 12 months on the
      psychomotor development of prematurely born infants].
AB  - AIMS: The link between deformational plagiocephaly and psychomotor development is
      a recurrent question in medical publications. Main publications concentrate on
      term infants, but there is a lack of data on the impact of deformational
      plagiocephaly on the long-term neurodevelopment of premature infants. We
      attempted to establish a possible relation between deformational plagiocephaly
      during the 1st year of life and the psychomotor score at 4 years in prematurely
      born infants. Other risk factors potentially impacting the psychomotor score were
      also studied. MATERIAL AND METHODS: A retrospective study of the files of the
      children followed by the "Naitre et Devenir Region PACA Ouest Corse Sud"
      healthcare network and included in the database allowed us to select a cohort of
      594 infants born prematurely at under 33 weeks of gestational age. These children
      were developmentally evaluated during the 1st year of life and at 4 years or age
      using the "EVAL Mater" test. The "Naitre et Devenir" network is following up
      infants born prematurely at under 33 weeks of gestation in the West Provence
      Alpes Cote d'Azur and South Corsica region, from discharge to 7 years. A group of
      170 specially trained pediatricians follow these infants developmentally at term,
      3, 6, 9, 12, 18, and 24 months of corrected age and 3, 4 5, 6, and 7 years. Data
      are collected in a specially designed database. RESULTS: There was no significant
      link between deformational plagiocephaly during the 1st year of life and a
      pathological psychomotor score at age 4, but some risk factors were demonstrated:
      male gender, birth at under 28 weeks of gestational age, weight at birth under
      1000g, having a Latal and Ferriero neuromotor score equal to or greater than 2 at
      3 months of corrected age, and to a lesser extent having a prescription for
      physiotherapy during the 1st year. CONCLUSION: The research on deformational
      plagiocephaly in the full-term infant suggests a relation between deformational
      plagiocephaly and developmental delay predominantly on the motor side, with an
      increased rate of special needs services at school age. The question is raised of
      whether deformational plagiocephaly is the cause of the delay or an early sign of
      cerebral anomaly with an early motor delay in full-term infants. The results
      suggest that deformational plagiocephaly in the prematurely born infant may not
      be related to neurodevelopmental delay but simply to the extended time spent in
      the supine position because of the early birth associated with physiological
      hypotonia and axial extension. Other risk factors such as male gender, birth
      before 28 weeks of gestation, weight less than 1000g, a Latal and Ferriero
      neuromotor score greater than 2 at 3 months of corrected age, and having a
      prescription for physiotherapy during the 1st year of life are strongly related
      to delayed psychomotor development at age 4.

PMID- 28754279
TI  - [G6PD deficiency in females with neonatal revelation. Report of four cases].
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human
      erythrocyte enzyme defect, estimated to affect approximately 4 million people
      worldwide. It is associated with severe neonatal hyperbilirubinemia, which may
      lead to bilirubin encephalopathy and kernicterus, and with hemolytic crisis. G6PD
      deficiency is an X-linked enzymopathy affecting hemizygous males, homozygous
      females, and also a subset of heterozygous females via chromosome X inactivation.
      We report four cases of female newborns with neonatal hyperbilirubinemia related
      to a G6PD deficiency and followed by the Centre national de reference en
      hemobiologie perinatale (CNRHP) from November 2013 to July 2014. Clinical and
      biological characteristics suggested G6PD deficiency (jaundice observed within
      the first 24h, severe hyperbilirubinemia, associated with regenerative hemolytic
      anemia, low response to phototherapy, ethnic origin of the parents from high
      incident geographical regions). The family investigations revealed a deficit in
      G6PD in one of the parents who was unaware of this deficit until then. This
      article aims to make neonatologists and pediatricians aware of the need to search
      for an etiology for any severe hyperbilirubinemia and to raise G6PD deficiency in
      male and female newborns in case of hyperbilirubinemia with hemolysis.

PMID- 28754280
TI  - [Prenatal diagnosis and management of two cases of bilateral ureteroceles on
      simplex ureters].
AB  - Ureterocele is a rare urologic disorder characterized by pseudocystic dilatation
      of the terminal submucosal ureter. Most cases of ureteroceles are associated with
      complete ureteral duplicity and ureterohydronephrosis, whereas ureteroceles on
      simplex ureters are rarer. The authors report two cases of bilateral ureteroceles
      on simplex ureters diagnosed prenatally at 30 and 32weeks gestation. Fetal
      ultrasound had revealed bilateral ureterohydronephrosis. The delivery was made at
      term and renal function was normal at birth. Radiological and isotopic studies of
      the urinary tract confirmed the diagnosis of bilateral ureteroceles on simplex
      ureters that were obstructive in one case and not obstructive in the other case.
      Both cases had urinary antiseptic treatment and neither had urinary infection.
      Endoscopic puncture with electrocoagulation of ureteroceles was performed at 8
      and 14months of age, respectively, with a simple postoperative course. Prenatal
      diagnosis of ureteroceles is essential to plan early multidisciplinary care to
      avoid long-term renal consequences.

PMID- 28754281
TI  - [Video: An innovation for developmental care in the neonatal intensive care
      unit].
AB  - INTRODUCTION: Our neonatal intensive care unit (NICU) was designed with a web
      camera system in eight private rooms and four open wards. This equipment was
      installed to both guarantee children's safety in the NICU and promote the bond
      between the child and his/her family through a viewing service permitted by an
      Internet access. METHOD: We evaluated the web-camera system in its 5th year with
      two types of users. The nursing staff was asked about use of the video and its
      impact on their management of NICU patients. Questionnaires for parents sought to
      determine how they used the system and their feelings about it. RESULTS: Ninety
      three percent of the nursing staff used the web-camera system to provide medical
      supervision or to comply with developmental care, mainly to respect the baby's
      natural rhythm by initiating care only when the baby showed signs of awakening.
      The web-camera system allowed them to observe the baby, verify his/her good body
      position, and spot discomfort situations. It helped provide a faster and
      personalized answer that was adjusted to the baby's needs. Sixty-one percent of
      the parents used the remote connection, half of them to present the child to the
      family. Only 17% of parents were embarrassed by the cameras; 88% of parents
      thought that the video was an additional safety device in NICU management.
      CONCLUSION: The web-camera system appeared to be an interesting technology in the
      NICU to support developmental care when children could be put in private rooms.
      It helped staff react faster to situations that created an inappropriate
      stimulation for the baby. It also allowed to them to respect the baby's natural
      rhythm. It reassured nursing staff and parents and it facilitated the baby's
      integration into the family.

PMID- 28754282
TI  - [Verticalization of the newborn during minimally invasive surfactant instillation
      procedures].

PMID- 28754283
TI  - [2017 pneumococcal vaccine recommendations of the Spanish Association of
      Paediatrics. Authors reply].

PMID- 28754284
TI  - Temporal transcriptome analysis of the white-rot fungus Obba rivulosa shows
      expression of a constitutive set of plant cell wall degradation targeted genes
      during growth on solid spruce wood.
AB  - The basidiomycete white-rot fungus Obba rivulosa, a close relative of Gelatoporia
      (Ceriporiopsis) subvermispora, is an efficient degrader of softwood. The
      dikaryotic O. rivulosa strain T241i (FBCC949) has been shown to selectively
      remove lignin from spruce wood prior to depolymerization of plant cell wall
      polysaccharides, thus possessing potential in biotechnological applications such
      as pretreatment of wood in pulp and paper industry. In this work, we studied the
      time-course of the conversion of spruce by the genome-sequenced monokaryotic O.
      rivulosa strain 3A-2, which is derived from the dikaryon T241i, to get insight
      into transcriptome level changes during prolonged solid state cultivation. During
      8-week cultivation, O. rivulosa expressed a constitutive set of genes encoding
      putative plant cell wall degrading enzymes. High level of expression of the genes
      targeted towards all plant cell wall polymers was detected at 2-week time point,
      after which majority of the genes showed reduced expression. This implicated non
      selective degradation of lignin by the O. rivulosa monokaryon and suggests high
      variation between mono- and dikaryotic strains of the white-rot fungi with
      respect to their abilities to convert plant cell wall polymers.

PMID- 28754285
TI  - Dynamics of parasitophorous vacuoles formed by the microsporidian pathogen
      Encephalitozoon cuniculi.
AB  - It has been a long-standing debate if sexual development occurs in the
      microsporidian lineages. Previous studies, including morphological observations,
      ploidy analysis, and the presence of a sex-related locus, provided evidence of
      possible extant of sexual development. This study presents another line of
      evidence by monitoring the parasitophorous vacuoles (PVs) formed by
      Encephalitozoon cuniculi. Time lapse observations of infection cycles of E.
      cuniculi revealed that multiple PVs can be formed in a single host cell and the
      PVs in the single cell can merge (fusion) or split (fission). The dynamics of PVs
      may provide a route for interactions between genetically distinct microsporidian
      isolates during host infections.

PMID- 28754286
TI  - Mitochondria are not captive bacteria.
AB  - Lynn Sagan's conjecture (1967) that three of the fundamental organelles observed
      in eukaryote cells, specifically mitochondria, plastids and flagella were once
      free-living primitive (prokaryotic) cells was accepted after considerable
      opposition. Even though the idea was swiftly refuted for the specific case of
      origins of flagella in eukaryotes, the symbiosis model in general was accepted
      for decades as a realistic hypothesis to describe the endosymbiotic origins of
      eukaryotes. However, a systematic analysis of the origins of the mitochondrial
      proteome based on empirical genome evolution models now indicates that 97% of
      modern mitochondrial protein domains as well their homologues in bacteria and
      archaea were present in the universal common ancestor (UCA) of the modern tree of
      life (ToL). These protein domains are universal modular building blocks of modern
      genes and genomes, each of which is identified by a unique tertiary structure and
      a specific biochemical function as well as a characteristic sequence profile.
      Further, phylogeny reconstructed from genome-scale evolution models reveals that
      Eukaryotes and Akaryotes (archaea and bacteria) descend independently from UCA.
      That is to say, Eukaryotes and Akaryotes are both primordial lineages that
      evolved in parallel. Finally, there is no indication of massive inter-lineage
      exchange of coding sequences during the descent of the two lineages. Accordingly,
      we suggest that the evolution of the mitochondrial proteome was autogenic
      (endogenic) and not endosymbiotic (exogenic).

PMID- 28754287
TI  - Lambda phage genetic switch as a system with critical behaviour.
AB  - Critical behaviour pervades scientific disciplines as diverse as geology, economy
      or sociology. The critical behaviour of cell control systems is an open issue
      whose role has not yet been fully explored. The control of the expression of
      lambda phage DNA in the host cell can be classified as a system with critical
      behaviour. Lambda phage is a virus that infects Escherichia coli. Its core genes
      maintain one of two states; lysogeny or lysis. Current knowledge of the lambda
      phage genetic network allows to build a computational model of transcriptional
      control of the genes involved in the lytic-lysogenic switch and to simulate the
      temporal changes of their expression. Here, we focused on the computational
      simulation of these gene expressions to demonstrate critical behaviour of the
      system.

PMID- 28754288
TI  - Involvement of NMDA receptors in the antidepressant-like effect of tramadol in
      the mouse forced swimming test.
AB  - Tramadol is an analgesic agent that is mainly used to treat moderate to severe
      pain. There is evidence that tramadol may have antidepressant property. However,
      the mechanisms underlying the antidepressant effects of tramadol have not been
      elucidated yet. Considering that fact that N-methyl-d-aspartate (NMDA) receptor
      signaling may play an important role in the pathophysiology of depression, the
      aim of the present study was to investigate the role of NMDA receptor signaling
      in the possible antidepressant-like effects of tramadol in the mouse forced
      swimming test (mFST). We found that tramadol exerted antidepressant-like effects
      at high dose (40mg/kg, intraperitoneally [i.p.]) in the mFST. Co-administration
      of non-effective doses of NMDA receptor antagonists (ketamine [1mg/kg, i.p.], MK
      801 [0.05mg/kg, i.p.], or magnesium sulfate [10mg/kg, i.p.]) with sub-effective
      dose of tramadol (20mg/kg, i.p.) exerted significant antidepressant-like effects
      in the mFST. The antidepressant-like effects of tramadol (40mg/kg) was also
      inhibited by pre-treatment with non-effective dose of the NMDA receptor agonist
      NMDA (75mg/kg, i.p.). Our data suggest a role for NMDA receptor signaling in the
      antidepressant-like effects of tramadol in the mFST.

PMID- 28754289
TI  - Dosimetric benefits of automation in the treatment of lower thoracic esophageal
      cancer: Is manual planning still an alternative option?
AB  - This study aimed to design automated volumetric-modulated arc therapy (VMAT)
      plans in Pinnacle auto-planning and compare it with manual plans for patients
      with lower thoracic esophageal cancer (EC). Thirty patients with lower thoracic
      EC were randomly selected for replanning VMAT plans using auto-planning in
      Pinnacle treatment planning system (TPS) version 9.10. Historical plans of these
      patients were then compared. Dose-volume histogram (DVH) statistics, dose
      uniformity, and dose homogeneity were analyzed to evaluate treatment plans. Auto
      planning was superior in terms of conformity index (CI) and homogeneity index
      (HI) for planning target volume (PTV), significantly improving 8.2% (p = 0.013)
      and 25% (p = 0.007) compared with manual planning, respectively, and decreasing
      dose of heart and liver irradiated by 20 to 40 Gy and 5 to 30 Gy, respectively (p
      < 0.05). Meanwhile, auto-planning further reduced the maximum dose (Dmax) of
      spinal cord by 6.9 Gy compared with manual planning (p = 0.000). Additionally,
      manual planning showed the significantly lower low-dose volume (V5) for the lung
      (p = 0.005). For auto-planning, the V5 of the lung was significantly associated
      with the relative volume index (the volume ratio of PTV to the lung), and the
      correlation coefficient (R) and p-value were 0.994 and 0.000. Pinnacle auto
      planning achieved superior target conformity and homogeneity and similar target
      coverage compared with historical manual planning. Most of organs at risk (OARs)
      sparing was significantly improved by auto-planning except for the V5 of the
      lung, and the low dose distribution was highly associated with PTV volume and
      lung volume in auto-planning.

PMID- 28754290
TI  - Molecular epigenetic targets for liver diseases: current challenges and future
      prospects.
AB  - Advanced chemotherapy fails to treat liver cancer but recent progress in
      understanding epigenetic modifications have witnessed promising clinical
      outcomes. Epigenetic alteration is the alteration of epigenomes (surrounding
      histone proteins) without changing the DNA sequence. Such epigenetic mechanisms
      include histone modifications such as methylation, acetylation, phosphorylation
      and sumoylation followed by changes in the genomic architecture. Current studies
      involving the understanding of small RNA molecules such as noncoding RNA and
      microRNA in modulating the chromatin architecture are explained in depth here,
      along with effects of some novel compounds from recent preclinical and clinical
      evidence. This review also discusses the current state-of-the-art strategies and
      the possible scope of investigation to improve the existing treatment methods for
      liver-related disorders.

PMID- 28754291
TI  - Mechanistic applications of click chemistry for pharmaceutical drug discovery and
      drug delivery.
AB  - The concept of click chemistry (CC), first introduced by K.B. Sharpless, has been
      widely adopted for use in drug discovery, novel drug delivery systems (DDS),
      polymer chemistry, and material sciences. In this review, we outline novel
      aspects of CC related to drug discovery and drug delivery, with a brief overview
      of molecular mechanisms underlying each click reaction commonly used by
      researchers, and the main patents that paved the way for further diverse
      medicinal applications. We also describe recent progress in drug discovery and
      polymeric and carbon material-based drug delivery for potential pharmaceutical
      applications and advancements based on the CC approach, and discuss some
      intrinsic limitations of this popular conjugation reaction. The use of CC is
      likely to significantly advance drug discovery and bioconjugation development.

PMID- 28754292
TI  - Freshwater Catfish Envenoming in a Tropical Country.
AB  - OBJECTIVE: Freshwater catfish are known to cause painful stings in humans. Stings
      usually cause mild envenomation and, in some instances, can lead to severe
      secondary bacterial infections. Sri Lanka is a tropical country where catfish
      stings are not rare. However, presenting signs and symptoms, complications, and
      management options are scarce in the literature. METHODS: A retrospective,
      descriptive, cross-sectional study was conducted by reviewing patient records in
      the university surgical units and surgical clinic in the teaching hospital in
      Anuradhapura, Sri Lanka, during 2015. RESULTS: Ten patients presented to the
      hospital following catfish stings. The common presenting features following
      stings were severe pain, swelling, and lymphadenopathy followed by cellulitis.
      Late complication such as tenosynovitis were also observed. CONCLUSIONS: Routine
      procedures are sufficient to reduce further complications. However, people who
      are at high risk of encountering catfish, and travelers visiting tropical
      countries, should be aware of the possibility of stings and take necessary
      precautions.

PMID- 28754293
TI  - Suicide Attempt by Ingestion of Rotenone-Containing Plant Extracts in French
      Polynesia: A Case Report.

PMID- 28754294
TI  - Prehospital Emergency Medicine at the Beach: What Is the Effect of Fins and
      Rescue Tubes in Lifesaving and Cardiopulmonary Resuscitation After Rescue?
AB  - OBJECTIVE: To analyze the influence of fins and rescue tube use in a water
      rescue, assessed by time and distance to salvage position, physiological
      parameters, and cardiopulmonary resuscitation (CPR). METHODS: Twenty professional
      lifeguards (10 men, 10 women) conducted 3 tests: a baseline test of 5 minutes of
      CPR and 2 water rescues, 1 without rescue equipment (NRE), and the other with
      fins and rescue tube (FRT). They also had to perform 5 minutes of CPR after each
      rescue. Time and distance of the rescues, physiological parameters (blood lactate
      concentration and heart rate), and quality of CPR were analyzed. RESULTS: CPR
      quality worsened by 26 to 28% (P < .001) after rescue. However, there were no
      differences using FRT. The use of rescue equipment reduced the time (FRT: 216+/
      57 seconds; NRE: 319+/-127 seconds; P < .001) and distance covered (FRT: 265+/-52
      m; NRE: 326+/-41 m; P < .001). No differences were found in lactate levels
      between FRT and NRE just after the rescues, but there were some after 5 minutes
      of subsequent CPR (FRT: 10.7+/-2.2 mmol/L; NRE: 12.6+/-1.8 mmol/L; P < .001).
      Comparing women with men, we found significant differences in lactate
      concentrations only in FRT (women: 9.6+/-1.4 mmol/L; men: 8.1+/-1.2 mmol/L; P =
      .031). CONCLUSIONS: The use of fins and rescue tube provides a comprehensive
      benefit in an aquatic emergency. However, FRT did not have any effect on the
      quality of the postrescue CPR.

PMID- 28754295
TI  - Blister Mystery.

PMID- 28754296
TI  - Assessing the Detection Limit of a Minority Solid-State Form of a Pharmaceutical
      by 1H Double-Quantum Magic-Angle Spinning Nuclear Magnetic Resonance
      Spectroscopy.
AB  - The lower detection limit for 2 distinct crystalline phases by 1H magic-angle
      spinning (MAS) solid-state nuclear magnetic resonance (NMR) is investigated for a
      minority amount of cimetidine (anhydrous polymorph A) in a physical mixture with
      the anhydrous HCl salt of cimetidine. Specifically, 2-dimensional 1H double
      quantum (DQ) MAS NMR spectra of polymorph A and the anhydrous HCl salt constitute
      fingerprints for the presence of each of these solid forms. For solid-state NMR
      data recorded at a 1H Larmor frequency of 850 MHz and a MAS frequency of 30 kHz
      on ~10 mg of sample, it is shown that, by following the pair of cross-peaks at a
      1H DQ frequency of 7.4 + 11.6 = 19.0 ppm that are unique to polymorph A, the
      level of detection for polymorph A in a physical mixture with the anhydrous HCl
      salt is a concentration of 1% w/w.

PMID- 28754297
TI  - Acute axonal neuropathy subtype of Guillain Barre syndrome in a French pediatric
      series: Adequate follow-up may require repetitive electrophysiological studies.
AB  - Different subtypes of Guillain Barre Syndromes (GBSs) are defined by their
      electrophysiological characteristics, acute inflammatory demyelinating neuropathy
      (AIDP), and acute motor/motor-sensory axonal forms (AMAN/AMSAN) with either
      reversible nerve conduction failure (RCF) or axonal degeneration. Our aim was to
      describe initial clinical and electrophysiological characteristics of axonal
      forms of GBS in a pediatric population and their short- and long-term evolution.
      Electroneuromyogram (ENMG) results were collected at diagnosis and at two months
      of evolution and interpreted using the recently proposed pattern of RCF vs axonal
      degeneration. Clinical evaluation was standardized using the GBS disability scale
      ("GBSds") at diagnosis, and then at 3, 6, and 12 months of evolution. Outcome was
      compared to those of patients with AIDP diagnosed within the same period. Eleven
      patients were included, among whom eight patients presenting with AMAN and three
      with AMSAN. Two subgroups were identified according to severity. Three patients
      had a severe form (GBSds >=2 at 12 months), two of them presenting an axonal
      degeneration on ENMG studies. Seven patients had a less severe form (GBSds <=1 at
      12 months), five of them with RCF on ENMG studies. Axonal forms had a more severe
      evolution than demyelinating forms (n = 17) at 3 months (median GBSds 3 and 2,
      respectively), 6 months (2 and 0), and 12 months (1 and 0), (p < 0,05). Axonal
      forms of GBS in children have a more severe global outcome than demyelinating
      forms. Axonal degeneration in two successive early ENMGs may be a prognostic
      factor of poor outcome.

PMID- 28754298
TI  - A novel SHANK3 interstitial microdeletion in a family with intellectual
      disability and brain MRI abnormalities resembling Unidentified Bright Objects.
AB  - BACKGROUND: SHANK3 mutations are responsible for Phelan-McDermid syndrome but
      they are also associated with autism and/or intellectual disability. CASE REPORT:
      We report a family with four affected individuals including the 37 year-old
      mother, her 12 year-old male monozygotic twins and 8 year-old daughter harboring
      a novel SHANK3 interstitial microdeletion. All four members presented with
      intellectual disability of variable severity. The twins showed brain
      abnormalities similar to Unidentified Bright Objects (UBOs), typically detected
      in patients with Neurofibromatosis type 1 (NF1), but they did not display
      causative mutations in NF1 gene. CONCLUSION: To date, this is the first report of
      an affected individual with SHANK3 interstitial deletion able to reproduce.
      Moreover, we found a previously unreported possible association between SHANK3
      deletion and UBOs-like lesions in the brain.

PMID- 28754300
TI  - Corrigendum to "Cloning and characterization of l-lactate dehydrogenase gene of
      Staphylococcus aureus" [Anaerobe 24 (2013) 43-48].

PMID- 28754299
TI  - Antimicrobial resistance in Neisseria gonorrhoeae: history, molecular mechanisms
      and epidemiological aspects of an emerging global threat.
AB  - Neisseria gonorrhoeae is the agent of gonorrhea, a sexually transmitted infection
      with an estimate from The World Health Organization of 78 million new cases in
      people aged 15-49 worldwide during 2012. If left untreated, complications may
      include pelvic inflammatory disease and infertility. Antimicrobial treatment is
      usually effective; however, resistance has emerged successively through various
      molecular mechanisms for all the regularly used therapeutic agents throughout
      decades. Detection of antimicrobial susceptibility is currently the most critical
      aspect for N. gonorrhoeae surveillance, however poorly structured health systems
      pose difficulties. In this review, we compiled data from worldwide reports
      regarding epidemiology and antimicrobial resistance in N. gonorrhoeae, and
      highlight the relevance of the implementation of surveillance networks to
      establish policies for gonorrhea treatment.

PMID- 28754301
TI  - High-dose-rate brachytherapy boost for prostate cancer: Comparison of three
      different fractionation schemes.
AB  - PURPOSE: Dose escalation for prostate cancer can be achieved with a combination
      of external beam radiotherapy (EBRT) and brachytherapy (BT) boost to increase
      local control. For high-dose-rate (HDR)-BT, optimal fractionation remains under
      debate. The objective was to assess the clinical outcome of three schemes of HDR
      BT boost. METHODS AND MATERIALS: Retrospective single institution data collection
      was performed. Patients received 46 Gy EBRT then an HDR-BT boost: 3 * 6 Gy, 2 * 9
      Gy, or 1 * 14 Gy. HDR needles were placed under general anesthesia with
      endorectal ultrasonography guidance. CT-scan and treatment were performed
      postoperatively. RESULTS: Between 2009 and 2012, 159 patients were included. Nine
      patients (5.7%) were low, 32 (20.1%) intermediate, and 118 (74.2%) high risk
      (D'Amico classification) without significant difference between the three BT
      schemes. With a median followup of 61 months, 5-year biochemical relapse-free
      survival, 5-year local relapse-free survival, 5-year metastases-free survival,
      and 5-year overall survival rates were 86.6% (SE 2.7%), 98.3% (SE 1%), 95.3% (SE
      1%), and 96.5% (SE 1.5%), respectively, with no significant difference between
      the BT schemes. The rates of acute >= G2 genitourinary and >=G2 gastrointestinal
      toxicities were 11.3% and 6.3%, respectively (p = NS). The rates of late
      genitourinary >= G2 and gastrointestinal >= G2 toxicities (at last followup) were
      9.4% and 0.6% with, respectively, 0.6% and 0% of G4 (p = NS). CONCLUSIONS:
      Hypofractionation up to a single-fraction HDR-BT boost for prostate cancer yields
      similar results in terms of biochemical control and late toxicity compared with
      two or three-fraction schemes. Single fraction HDR-BT appears acceptable for
      boosting prostate cancer after definitive EBRT.

PMID- 28754302
TI  - Immunometabolic and Lipidomic Markers Associated With the Frailty Index and
      Quality of Life in Aging HIV+ Men on Antiretroviral Therapy.
AB  - Chronic immune activation persists despite antiretroviral therapy (ART) in HIV+
      individuals and underpins an increased risk of age-related co-morbidities. We
      assessed the Frailty Index in older HIV+ Australian men on ART. Immunometabolic
      markers on monocytes and T cells were analyzed using flow cytometry, plasma
      innate immune activation markers by ELISA, and lipidomic profiling by mass
      spectrometry. The study population consisted of 80 HIV+ men with a median age of
      59 (IQR, 56-65), and most had an undetectable viral load (92%). 24% were frail,
      and 76% were non-frail. Frailty was associated with elevated Glucose transporter
      1 (Glut1) expression on the total monocytes (p=0.04), increased plasma levels of
      innate immune activation marker sCD163 (OR, 4.8; CI 1.4-15.9, p=0.01),
      phosphatidylethanolamine PE(36:3) (OR, 5.1; CI 1.7-15.5, p=0.004) and
      triacylglycerol TG(16:1_18:1_18:1) (OR, 3.4; CI 1.3-9.2, p=0.02), but decreased
      expression of GM3 ganglioside, GM3(d18:1/18:0) (OR, 0.1; CI 0.0-0.6, p=0.01) and
      monohexosylceramide HexCerd(d18:1/22:0) (OR, 0.1; CI 0.0-0.5, p=0.004). There is
      a strong inverse correlation between quality of life and the concentration of
      PE(36:3) (rho=-0.33, p=0.004) and PE(36:4) (rho=-0.37, p=0.001). These data
      suggest that frailty is associated with increased innate immune activation and
      abnormal lipidomic profile. These markers should be investigated in larger,
      longitudinal studies to determine their potential as biomarkers for frailty.

PMID- 28754303
TI  - Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a
      Cytosolic Cross-presentation Pathway.
AB  - Cyclic di-nucleotides (CDN) are potent stimulators of innate and adaptive immune
      responses. Cyclic di-AMP (CDA) is a promising adjuvant that generates humoral and
      cellular immunity. The strong STING-dependent stimulation of type I IFN
      represents a key feature of CDA. However, recent studies suggested that this is
      dispensable for adjuvanticity. Here we demonstrate that stimulation of IFN-gamma
      secreting CD8+ cytotoxic T lymphocytes (CTL) is significantly decreased after
      vaccination in the absence of type I IFN signaling. The biological significance
      of this CTL response was confirmed by the stimulation of MHC class I-restricted
      protection against influenza virus challenge. We show here that type I IFN (and
      not TNF-alpha) is essential for CDA-mediated cross-presentation by a cathepsin
      independent, TAP and proteosome dependent cytosolic antigen processing pathway,
      which promotes effective cross-priming and further CTL induction. Our data
      clearly demonstrate that type I IFN signaling is critical for CDN-mediated cross
      presentation.

PMID- 28754304
TI  - A Natural CCR2 Antagonist Relieves Tumor-associated Macrophage-mediated
      Immunosuppression to Produce a Therapeutic Effect for Liver Cancer.
AB  - Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract
      with limited therapeutic choices. Although sorafenib, an orally administered
      multikinase inhibitor, has produced survival benefits for patients with advanced
      HCC, favorable clinical outcomes are limited due to individual differences and
      resistance. The application of immunotherapy, a promising approach for HCC is
      urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a
      potential immunotherapeutic target. Here, we report that a natural product from
      Abies georgei, named 747 and related in structure to kaempferol, exhibits
      sensitivity and selectivity as a CCR2 antagonist. The specificity of 747 on CCR2
      was demonstrated via calcium flux, the binding domain of CCR2 was identified in
      an extracellular loop by chimera binding assay, and in vivo antagonistic activity
      of 747 was confirmed through a thioglycollate-induced peritonitis model. In
      animals, 747 elevated the number of CD8+ T cells in tumors via blocking tumor
      infiltrating macrophage-mediated immunosuppression and inhibited orthotopic and
      subcutaneous tumor growth in a CD8+ T cell-dependent manner. Further, 747
      enhanced the therapeutic efficacy of low-dose sorafenib without obvious toxicity,
      through elevating the numbers of intra-tumoral CD8+ T cells and increasing death
      of tumor cells. Thus, we have discovered a natural CCR2 antagonist and have
      provided a new perspective on development of this antagonist for treatment of
      HCC. In mouse models of HCC, 747 enhanced the tumor immunosuppressive
      microenvironment and potentiated the therapeutic effect of sorafenib, indicating
      that the combination of an immunomodulator with a chemotherapeutic drug could be
      a new approach for treating HCC.

PMID- 28754305
TI  - Making Research One of Our Key Priorities.

PMID- 28754306
TI  - Episodic memory following deep brain stimulation of the ventral anterior limb of
      the internal capsule and electroconvulsive therapy.
AB  - BACKGROUND: Electroconvulsive Therapy (ECT) and Deep Brain Stimulation (DBS) are
      effective treatments for patients with treatment-resistant depression (TRD).
      However, a common side effect of ECT is autobiographical memory loss (e.g.,
      personal experiences), whereas the impact of DBS on autobiographical memories has
      never been established. OBJECTIVE: Comparing autobiographical memories following
      DBS and ECT. METHODS: In two hospitals in The Netherlands, we interviewed 25 TRD
      patients treated with DBS of the ventral anterior limb of the internal capsule
      (vALIC), 14 TRD patients treated with ECT and 22 healthy controls (HC) with the
      Autobiographical Memory Inventory - Short Form (AMI-SF) in a prospective,
      longitudinal study between March 2010 and August 2016. Patients treated with DBS
      were interviewed before surgery, after surgery, and twice during treatment over
      122.7 (SD: +/-22.2) weeks. Patients treated with ECT were tested before ECT,
      after six right unilateral (RUL) ECT sessions and twice following ECT over 65.1
      (+/-9.3) weeks. Controls were tested four times over 81.5 (+/-15.6) weeks.
      RESULTS: Compared to HC, the AMI-SF score decreased faster in both TRD groups (P
      < 0.001). More specifically, AMI-SF score decreased in a comparable rate as HC
      after DBS surgery, but decreased more during treatment. The AMI-SF decrease in
      the ECT group was larger than both the DBS and HC groups. CONCLUSIONS: Both ECT
      and vALIC DBS result in a faster autobiographical memory decline compared to HC.
      DBS might have a negative impact on autobiographical memories, although less so
      than ECT. Future work should dissect whether DBS or characteristics of TRD cause
      this decline.

PMID- 28754307
TI  - Within-person changes in salivary testosterone and physical characteristics of
      puberty predict boys' daily affect.
AB  - Recent investigations highlighted the role of within-person pubertal changes for
      adolescents' behavior. Yet, little is known about effects on adolescents' daily
      affect, particularly regarding the hormonal changes underlying physical changes
      during puberty. In a study with 148 boys aged 10 to 20years, we tested whether
      within-person physical and hormonal changes over eight months predicted everyday
      affect fluctuations, measured with experience sampling. As expected, greater
      within-person changes in testosterone (but not in dehydroepiandrosterone) were
      associated with higher affect fluctuations in daily life. Additionally, greater
      physical changes predicted higher affect fluctuations for individuals in the
      beginning of puberty. The findings demonstrate the relevance of physical and
      hormonal changes in boys' affective (in)stability.

PMID- 28754308
TI  - Association between metabolic syndrome and fragmented QRS complexes: Speckle
      tracking echocardiography study.
AB  - BACKGROUND: Metabolic syndrome (MetS) is an endocrinological disease with both
      metabolic and physiological components. Previous studies have shown a
      relationship between MetS and left ventricular (LV) dysfunction. A fragmented QRS
      (fQRS) is a reliable electrocardiogram (ECG) finding with the importance of an
      indicator of myocardial fibrosis and scarring. In this study, we examined the
      utility of speckle tracking echocardiography (STE) in assessing LV function in
      MetS patients with fQRS. METHODS: The 164 consecutive MetS patients included in
      the study. They were separated into two groups; those with (n=33) and those
      without (n=131) fQRS. The two groups were compared by obtaining LV strain values
      with STE. RESULTS: Statistically significant differences between the fQRS (-) and
      fQRS (+) groups were identified for LV global longitudinal strain (LV-GLS)
      (p<0.001), maximum left atrial volume index (maxLAVI) (p<=0.001), strain rate
      during isovolumic relaxation period (SRivr) (p<0.001), and the E/SRivr ratio
      (p<0.001). In the multiple linear regression analysis, fQRS (beta=-1.456,
      p=0.003), diabetes mellitus (beta=-0.973, p=0.015), hypertension (beta=-0.820,
      p=0.015) and MaxLAVI (beta=-0.142, p=0.018) were independent predictors of LV
      GLS. However, fQRS (beta=21.995, p<0.001), MaxLAVI (beta=3.090, p<0.001), and
      E/Em ratio (beta=3.326, p<0.001) were also independent predictors of E/SRivr.
      CONCLUSIONS: The results of this study showed that LV dysfunction was more common
      in MetS patients with fQRS. MetS patients, and especially those who are fQRS (+),
      should thus be closely monitored for subclinical LV systolic and diastolic
      dysfunction.

PMID- 28754311
TI  - Correction.

PMID- 28754310
TI  - A single-institution assessment of superficial spreading melanoma (SSM) in the
      pediatric population: Molecular and histopathologic features compared with adult
      SSM.
AB  - BACKGROUND: The epidemiology of pediatric melanoma is distinct from that seen in
      adults. This is more distinguishable when pediatric patients are separated into
      prepubertal and adolescent groups. OBJECTIVE: In this study, we compared
      epidemiologic, clinical, histologic, and molecular characteristics of pediatric
      superficial spreading melanoma (SSM) in prepubertal and adolescent patients to
      that in adults. METHOD: We reviewed our database for pediatric melanomas,
      comparing SSM data between pediatric and adult cases for pathologic stage at
      presentation, ratio of radial to vertical growth phase, average Breslow depth and
      mitotic index, and frequency of fluorescence in situ hybridization (FISH)
      positivity. RESULTS: Of 84 pediatric melanomas, 38 were SSM, and 5 of the latter
      (6%) were prepubertal. There were no significant differences when pediatric and
      adult SSM were compared for stage at presentation, ratio of radial to vertical
      growth phase, average Breslow depth and mitotic count, or frequency of FISH
      positivity. A significant difference was detected for SSM arising from a
      precursor nevus (80% of pediatric cases versus 30% of adult cases). LIMITATIONS:
      Follow-up time was limited for both cohorts. CONCLUSIONS: SSM melanoma is
      infrequent in childhood, particularly in the prepubertal years. Features such as
      tumor stage, Breslow depth, mitotic activity, and FISH positivity suggest
      morphologic and molecular characteristics similar to those of adult SSM.

PMID- 28754309
TI  - Retinoic acid, CYP26, and drug resistance in the stem cell niche.
AB  - The bone marrow niche is essential for hematopoietic stem cells to maintain
      lifelong blood production by balancing their self-renewal and differentiation.
      Hematologic malignancies have a similar hierarchical organization to their normal
      counterparts, with rare populations of cancer stem cells that rely on the
      microenvironment to survive and propagate their differentiated malignant
      progenitor cells. Cancer cells alter their microenvironment to create a
      supportive niche, where they endure chemotherapy, survive as minimal residual
      disease (MRD), and eventually prevail at relapse. Powerful morphogens, such as
      retinoids, Wnt/betacatenin, Notch, and Hedgehog, control stem cell fates across
      tissues, including normal and malignant hematopoiesis. The molecular
      conversations between these pathways and the mechanisms that control their
      activity and create gradients at cellular scale remain a mystery. Here, we
      discuss accumulating evidence suggesting that cytochrome P450 (CYP26), the
      primary retinoid-inactivating enzyme, plays a critical role in the integration of
      two of these molecular programs: the retinoid and Hedgehog pathways. Induction of
      stromal CYP26 by either one of these pathways limits retinoic acid concentration
      in the stem cell niche, with profound effects on tissue homeostasis and drug
      resistance. Bypassing this gatekeeping mechanism holds promise for overcoming
      drug resistance and improving clinical outcomes in hematological malignancies and
      cancer in general.

PMID- 28754312
TI  - Exercise in an animal model of Parkinson's disease: Motor recovery but not
      restoration of the nigrostriatal pathway.
AB  - Many clinical studies have reported on the benefits of exercise therapy in
      patients with Parkinson's disease (PD). Exercise cannot stop the progression of
      PD or facilitate the recovery of dopamine (DA) neurons in the substantia nigra
      pars compacta (SNpc) (Bega et al., 2014). To tease apart this paradox, we
      utilized a progressive MPTP (1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine) mouse
      model in which we initiated 4weeks of treadmill exercise after the completion of
      toxin administration (i.e., restoration). We found in our MPTP/exercise (MPTP+EX)
      group several measures of gait function that recovered compared to the MPTP only
      group. Although there was a small recovery of tyrosine hydroxylase (TH) positive
      DA neurons in the SNpc and terminals in the striatum, this increase was not
      statistically significant. These small changes in TH could not explain the
      improvement of motor function. The MPTP group had a significant 170% increase in
      the glycosylated/non-glycosylated dopamine transporter (DAT) and a 200% increase
      in microglial marker, IBA-1, in the striatum. The MPTP+EX group showed a nearly
      full recovery of these markers back to the vehicle levels. There was an increase
      in GLT-1 levels in the striatum due to exercise, with no change in striatal BDNF
      protein expression. Our data suggest that motor recovery was not prompted by any
      significant restoration of DA neurons or terminals, but rather the recovery of
      DAT and dampening the inflammatory response. Although exercise does not promote
      recovery of nigrostriatal DA, it should be used in conjunction with
      pharmaceutical methods for controlling PD symptoms.

PMID- 28754313
TI  - The 5-HT4 receptor-mediated inhibition of visceral nociceptive neurons in the rat
      caudal ventrolateral medulla.
AB  - Activation of the serotonin type 4 (5-HT4) receptors has been reported to improve
      abdominal pain in patients with functional gastrointestinal disorders and reduce
      visceral nociception in animal models. Earlier studies have proposed that 5-HT4
      agonist can produce visceral analgesia by acting at the supraspinal level, but
      the underlying neuronal mechanisms remain unclear. The caudal ventrolateral
      medulla (CVLM) is the first site for processing of visceral nociceptive signals
      ascending via spinal pathways and an important component of the endogenous pain
      modulatory system. Therefore, the objective of the present study was to examine
      whether activation of 5-HT4 receptors can affect the visceral pain-related
      neurons in the CVLM. In urethane-anesthetized adult male Wistar rats, we
      evaluated the effects of a 5-HT4 receptor agonist, BIMU8 on ongoing firing of the
      CVLM neurons and their excitatory responses to noxious colorectal distension
      (CRD, 80mmHg). The drug's effect was also tested on blood pressure reactions
      induced by CRD-a general physiological measure of visceral nociception.
      Intravenous administration of BIMU8 (0.5, 1 or 2mg/kg) produced dose-dependent
      suppression of both the ongoing and CRD-evoked activities of the CVLM neurons and
      simultaneously attenuated the depressor hemodynamic reaction to CRD. The
      compound's inhibitory effect was almost completely eliminated by
      intracerebroventricular pretreatment with GR113808, a selective 5-HT4 antagonist,
      indicating the preferential involvement of supraspinal 5-HT4 receptors. Results
      indicate that visceral nociceptive transmission through the caudal medulla is
      negatively modulated by descending 5-HT4-dependent mechanisms. These findings can
      contribute to a deeper understanding of supraspinal processing of pain signals
      from the abdomen.

PMID- 28754314
TI  - The role of Celsr3 in the development of central somatosensory projections from
      dorsal root ganglia.
AB  - Dorsal root ganglion (DRG) neurons receive peripheral somatosensory information
      and send orderly projections to second-order relay nuclei in the spinal cord and
      in the brainstem. Atypical cadherin Celsr3 is known to play a critical role in
      wiring of several central and peripheral axons. Although Celsr3 mRNA is heavily
      expressed in DRG neurons, its role in the development of somatosensory
      projections remains unexplored. Here we assessed the role of Celsr3 in DRG using
      conditional gene inactivation in crosses with Wnt1-Cre mice. Using Celsr3-GFP
      transgenic mice, we found that Celsr3 was highly expressed in different DRG
      cells, such as Pavalbumin-, TrkB-, and calcitonin gene-related peptide (CGRP)
      positive neurons. Wnt1-Cre;Celsr3f/- animals survived for a few weeks and looked
      smaller than littermate controls. DiI tracing showed that early DRG axons entered
      the spinal cord and reached spinal cord targets similarly in mutant and control
      mice. CGRP-positive fiber density was significantly decreased in lamina I in the
      mutant versus control spinal cord at postnatal day (P) 7 and P14. Furthermore,
      more Pavalbumin-positive fibers invaded the gray matter and made more contacts
      with spinal motor neurons in mutant than in control samples. Behavioral analysis
      showed that mutant animals were less sensitive to pain and more sensitive to
      mechanical stimulation than controls. In conclusion, Celsr3 is dispensable for
      the patterning of central DRG projections, but it regulates for the fine mapping
      of sensory fibers in the gray matter, which is important for somatosensory
      processing.

PMID- 28754315
TI  - Insights into the phosphatidylcholine and phosphatidylethanolamine biosynthetic
      pathways in Leishmania parasites and characterization of a choline kinase from
      Leishmania infantum.
AB  - The protozoan parasite Leishmania infantum is a causative agent of the disease
      visceral leishmaniasis, which can be fatal if not properly treated.
      Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) biosynthesis pathways
      are attractive targets for new antileishmanial compounds since these Leishmania
      cell membrane phospholipids are important for parasite morphology and physiology.
      In this work we observed Leishmania synthesize PC and PE from extracellular
      choline and ethanolamine, respectively, suggesting the presence of CDP-choline
      and CDP-ethanolamine pathways. In addition, Leishmania converted PE to PC,
      indicating the parasite possesses phosphatidylethanolamine N-methyltransferase
      (PEMT) activity. The first step in the biosynthesis of PC or PE requires the
      phosphorylation of choline or ethanolamine by a kinase. We cloned the gene
      encoding a putative choline/ethanolamine kinase from Leishmania infantum and
      expressed and purified the encoded recombinant protein. The enzyme possesses
      choline kinase activity with a Vmax of 3.52MUmol/min/mg and an apparent Km value
      of 0.089mM with respect to choline. The enzyme can also phosphorylate
      ethanolamine in vitro, but the apparent Km for ethanolamine is 850-fold greater
      than for choline. In an effort to probe requirements for small molecule
      inhibition of Leishmania choline kinase, the recombinant enzyme was evaluated for
      the ability to be inhibited by novel quaternary ammonium salts. The most
      effective inhibitor was N-iodomethyl-N,N,-dimethyl-N-(6,6-diphenyl hex-5-en-1
      yle) ammonium iodide, denoted compound C6. In the presence of 4mM compound C6,
      the Vmax/Km decreased to approximately 1% of the wild-type catalytic efficiency.
      In addition, in Leishmania cells treated with compound C6 choline transport was
      inhibited.

PMID- 28754316
TI  - Patterns and functional implications of platelets upon tumor "education".
AB  - While platelets are traditionally recognized to play a predominant role in
      hemostasis and thrombosis, increasing evidence verifies its involvement in
      malignancies. As a component of the tumor microenvironment, platelets influence
      carcinogenesis, tumor metastasis and chemotherapy efficiency. Platelets status is
      thus predictable as a hematological biomarker of cancer prognosis and a hot
      target for therapeutic intervention. On the other hand, the role of circulating
      tumor cells (CTCs) as an inducer of platelet activation and aggregation has been
      well acknowledged. The cross-talk between platelets and CTCs is reciprocal on
      that the CTCs activate platelets while platelets contribute to CTCs' survival and
      dissemination. This review covers some of the current issues related to the loop
      between platelets and tumor aggression, including the manners of tumor cells in
      "educating" platelets and biofunctional alterations of platelets upon tumor
      "education". We also highlight the potential clinical applications on the
      interplay between tumors and platelets. Further studies with well-designed
      prospective multicenter trials may contribute to clinical "liquid biopsy"
      diagnosis by evaluating the global changes of platelets.

PMID- 28754317
TI  - Natural antisense transcript TPM1-AS regulates the alternative splicing of
      tropomyosin I through an interaction with RNA-binding motif protein 4.
AB  - LncRNAs play a vital role in alternative splicing of target genes. However, the
      mechanisms underlying lncRNAs involvement in splicing are poorly understood. In
      the present study, we identified a previously uncharacterized lncRNA, which is
      denoted as TPM1-AS, is reverse-transcribed from the fourth intronic region of the
      tropomyosin I (TPM1). In situ hybridization and RNA immunoprecipitation assays
      demonstrated that TPM1-AS was located in the nucleus and interacted with RNA
      binding motif protein 4 (RBM4) in human esophageal cancer cells. TPM1-AS
      overexpression or RBM4 knockdown decreased endogenous exon 2a expression of TPM1,
      resulting in specifically down-regulation of TPM1variant V2 and V7 in human
      esophageal cancer cells. Mechanismly, the interaction of TPM1-AS with RBM4
      hindered binding of RBM4 to TPM1 pre-mRNA and inhibited RBM4 to promote
      endogenous exon 2a inclusion of TPM1. Importantly, overexpression of TPM1-AS
      inhibited migration and filopodium formation, whereas TPM1variant V2 and V7
      promoted these behaviors of human esophageal cancer cells. Taken together, the
      results suggest that a natural antisense TPM1-AS regulates the alternative
      splicing of TPM1 through an interaction with RBM4 and involves in TPM1-mediated
      filopodium formation and migration of cancer cells.

PMID- 28754318
TI  - Anion inhibitors of the beta-carbonic anhydrase from the pathogenic bacterium
      responsible of tularemia, Francisella tularensis.
AB  - A beta-class carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium
      Francisella tularensis (FtubetaCA) was cloned and purified, and the anion
      inhibition profile was investigated. Based on the measured kinetic parameters for
      the enzyme catalyzed CO2 hydration reaction (kcat of 9.8*105s-1 and a kcat/KM of
      8.9*107M-1s-1), FtubetaCA is a highly effective enzyme. The activity of FtubetaCA
      was not inhibited by a range of anions that do not typically coordinate Zn(II)
      effectively, including perchlorate, tetrafluoroborate, and hexafluorophosphate.
      Surprisingly, some anions which generally complex well with many cations,
      including Zn(II), also did not effectively inhibit FtubetaCA, e.g., fluoride,
      cyanide, azide, nitrite, bisulphite, sulfate, tellurate, perrhenate,
      perrhuthenate, and peroxydisulfate. However, the most effective inhibitors were
      in the range of 90-94uM (sulfamide, sulfamic acid, phenylarsonic and
      phenylboronic acid). N,N-Diethyldithiocarbamate (KI of 0.31mM) was a moderately
      potent inhibitor. As Francisella tularensis is the causative agent of tularemia,
      the discovery of compounds that can interfere with the life cycle of this
      pathogen may result in novel opportunities to fight antibiotic drug resistance.

PMID- 28754319
TI  - A study to develop clinical decision rules for the use of radiography in wrist
      trauma: Karadeniz wrist rules.

PMID- 28754320
TI  - Efficacy of vasopressin-epinephrine compared to epinephrine alone for out of
      hospital cardiac arrest patients: A systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to conduct a meta-analysis to evaluate the
      efficacy of vasopressin-epinephrine compared to epinephrine alone in patients who
      suffered out-of-hospital cardiac arrest (OHCA). METHODS: Relevant studies up to
      February 2017 were identified by searching in PubMed, EMBASE, the Cochrane
      Library, Wanfang for randomized controlled trials(RCTs) assigning adults with
      cardiac arrest to treatment with vasopressin-epinephrine (VEgroup) vs adrenaline
      (epinephrine) alone (E group). The outcome point was return of spontaneous
      circulation (ROSC) for patients suffering from OHCA. Heterogeneity, subgroup
      analysis, sensitivity analysis and publication bias were explored. RESULTS:
      Individual patient data were obtained from 5047 participants who experienced OHCA
      in nine studies. Odds ratios (ORs) were calculated using a random-effects model
      and results suggested that vasopressin-epinephrine was associated with higher
      rate of ROSC (OR=1.67, 95% CI=1.13-2.49, P<0.00001, and total I2=83%). Subgroup
      showed that vasopressin-epinephrine has a significant association with
      improvements in ROSC for patients from Asia (OR=3.30, 95% CI=1.30-7.88); but for
      patients from other regions, there was no difference between vasopressin
      epinephrine and epinephrine alone (OR=1.07, 95% CI=0.72-1.61). CONCLUSION:
      According to the pooled results of the subgroup, combination of vasopressin and
      adrenaline can improve ROSC of OHCA from Asia, but patients from other regions
      who suffered from OHCA cannot benefit from combination of vasopressin and
      epinephrine.

PMID- 28754321
TI  - Crystal structure of Pisum arvense seed lectin (PAL) and characterization of its
      interaction with carbohydrates by molecular docking and dynamics.
AB  - The Pisum arvense lectin (PAL), a legume protein belonging to the Vicieae tribe,
      is capable of specific recognition of mannose, glucose and its derivatives
      without altering its structure. In this work, the three-dimensional structure of
      PAL was determined by X-ray crystallography and studied in detail by a
      combination of molecular docking and molecular dynamics (MD). Crystals belonging
      to monoclinic space group P21 were grown by the vapor diffusion method at 293 K.
      The structure was solved at 2.16 A and was similar to that of other Vicieae
      lectins. The structure presented Rfactor and Rfree of 17.04% and 22.08%,
      respectively, with all acceptable geometric parameters. Molecular docking was
      performed to analyze interactions of the lectin with monosaccharides,
      disaccharides and high-mannose N-glycans. PAL demonstrated different affinities
      on carbohydrates, depending on bond orientation and glycosidic linkage present in
      ligands. Furthermore, the lectin interacted with representative N-glycans in a
      manner consistent with the biological effects described for Vicieae lectins.
      Carbohydrate-recognition domain (CRD) in-depth analysis was performed by MD,
      describing the behavior of CRD residues in complex with ligand, stability,
      flexibility of the protein over time, CRD volume and topology. This is a first
      report of its kind for a lectin of the Vicieae tribe.

PMID- 28754322
TI  - Characterization of secondary structure and lipid binding behavior of N-terminal
      saposin like subdomain of human Wnt3a.
AB  - Wnt signaling is essential for embryonic development and adult homeostasis in
      multicellular organisms. A conserved feature among Wnt family proteins is the
      presence of two structural domains. Within the N-terminal (NT) domain there
      exists a motif that is superimposable upon saposin-like protein (SAPLIP) family
      members. SAPLIPs are found in plants, microbes and animals and possess lipid
      surface seeking activity. To investigate the function of the Wnt3a saposin-like
      subdomain (SLD), recombinant SLD was studied in isolation. Bacterial expression
      of this Wnt fragment was achieved only when the core SLD included 82 NT residues
      of Wnt3a (NT-SLD). Unlike SAPLIPs, NT-SLD required the presence of detergent to
      achieve solubility at neutral pH. Deletion of two hairpin loop extensions present
      in NT-SLD, but not other SAPLIPs, had no effect on the solubility properties of
      NT-SLD. Far UV circular dichroism spectroscopy of NT-SLD yielded 50-60% alpha
      helix secondary structure. Limited proteolysis of isolated NT-SLD in buffer and
      detergent micelles showed no differences in cleavage kinetics. Unlike
      prototypical saposins, NT-SLD exhibited weak membrane-binding affinity and lacked
      cell lytic activity. In cell-based canonical Wnt signaling assays, NT-SLD was
      unable to induce stabilization of beta-catenin or modulate the extent of beta
      catenin stabilization induced by full-length Wnt3a. Taken together, the results
      indicate neighboring structural elements within full-length Wnt3a affect SLD
      conformational stability. Moreover, SLD function(s) in Wnt proteins appear to
      have evolved away from those commonly attributed to SAPLIP family members.

PMID- 28754323
TI  - The UbiX-UbiD system: The biosynthesis and use of prenylated flavin (prFMN).
AB  - The UbiX-UbiD system consists of the flavin prenyltransferase UbiX that produces
      prenylated FMN that serves as the cofactor for the (de)carboxylase UbiD. Recent
      developments have provided structural insights into the mechanism of both
      enzymes, detailing unusual chemistry in each case. The proposed reversible 1,3
      dipolar cycloaddition between the cofactor and substrate serves as a model to
      explain many of the key UbiD family features. However, considerable variation
      exists in the many branches of the UbiD family tree.

PMID- 28754324
TI  - Histopathological and clinical evaluation of chronic spontaneous urticaria
      patients with neutrophilic and non-neutrophilic cutaneous infiltrate.
AB  - BACKGROUND: Chronic urticaria has an expressive prevalence in general population,
      especially in adults, and is defined by the presence of intermittent hives for
      six weeks or longer. Our study aims to characterize the histological patterns of
      chronic spontaneous urticaria, based on the inflammatory cell infiltrate, and
      correlate them to laboratory exams. METHODS: It was performed a retrospective
      analysis of laboratory, histopathology and direct immunofluorescence data of 93
      patients with chronic urticaria. For histopathological analysis, cell count was
      performed in four fields at high magnification (*400) for each specimen. The
      resulting cell count medians were submitted to statistical analysis and, then,
      were correlated to laboratorial findings. RESULTS: We found a female predominance
      (76.34%) of chronic urticaria cases, and an average age of 42.5 years (SD +/-
      15). Two histological groups were distinctive: 1) chronic urticaria with
      predominance of neutrophils or eosinophils - N (%) = 39 (42.4%) - and 2) chronic
      urticaria with predominance of lymphocytes - N (%) = 53 (57.6%). There was not
      significant correlation between histological groups and laboratorial tests.
      Moreover, direct immunofluorescence was positive in 21 (33,87%) from 62 patients.
      CONCLUSIONS: There is not enough scientific evidence to support neutrophilic
      urticaria as a solid, separate entity.

PMID- 28754325
TI  - Subtraction of natural radiation contribution from gamma-ray spectra measured by
      HPGe detector.
AB  - A method is described for the subtraction of Monte Carlo simulated detector
      spectra of the contribution of natural radiation to measured detector spectra
      aiming to decrease the decision threshold for the detection of artificial
      radionuclides. HPGe detector spectra were simulated for selected naturally
      occurring radionuclides deposited onto a filter used for aerosol collection in a
      newly developed airborne radioactivity monitoring system. Stepwise, the simulated
      spectra were fitted to the actually acquired gamma-ray spectrum and the decision
      threshold was determined. Contribution of cosmic rays background was also
      estimated.

PMID- 28754326
TI  - Diagnosis of acute overt gastrointestinal bleeding with CT-angiography:
      Comparison of the diagnostic performance of individual acquisition phases.
AB  - PURPOSE: To compare the respective values of arterial phase, portal venous phase
      and combination of phases using 64-section multidetector computed tomography
      (MDCT) for diagnosing acute overt gastrointestinal bleeding (AOGIB). PATIENTS AND
      METHODS: Forty-nine patients with AOGIB were included. There were 30 men and 19
      women, with a mean age of 65.4+/-15.6 (SD) years [range, 34-91years]. Two
      observers reviewed MDCT examinations in consensus for presence of active
      bleeding, location of bleeding site and nature of causative lesion. The different
      acquisition phases were reviewed independently. RESULTS: AOGIB was identified in
      28/49 patients (57%) with the multiphasic set, in 26/49 patients (53%) with
      arterial phase and in 25/49 patients (51%) with portal venous phase. Multiphasic
      set helped locate the bleeding site in 40/49 patients (82%). The cause was
      elucidated in 23/49 patients (47%) with multiphasic set. The differences between
      set performances were not statistically significant. Sensitivity for depicting
      AOGIB with the multiphasic set was 92% and specificity was 76%. CONCLUSION:
      Multiphasic 64-section MDCT has high diagnostic performances in patients with
      AOGIB. Further studies with a larger population are needed to reach statistical
      significance and demonstrate better diagnostic performance of multiphasic MDCT in
      comparison with the arterial or portal phase alone.

PMID- 28754327
TI  - Cognitive enhancement: A system view.

PMID- 28754328
TI  - Age-related levels of fecal M2-pyruvate kinase in children with cystic fibrosis
      and healthy children 0 to 10years old.
AB  - BACKGROUND: The pathogenesis of gut inflammation, bacterial dysbiosis and
      increased rates of malignancy in CF is unclear. Fecal M2-pyruvate kinase (M2-PK)
      is a biomarker indicative of cellular proliferation that may be raised in
      intestinal malignancy and inflammation. Biomarkers, including M2-PK, may be
      useful in assessing effects of novel therapies on the gastrointestinal tract.
      METHODS: M2-PK was measured in stools collected from patients with CF and HC (0
      10years). Linear mixed model analysis was used. RESULTS: M2-PK levels did not
      significantly change in children with CF (36 patients, 77 samples) (P=0.998) or
      HC (45 patients, 45 samples) (P=0.21), over the age range 0-10years. Patients
      with CF had elevated M2-PK compared to HC (median [IQR; range]: 10.7 [5.7-28.6;
      1.0-239.1] (n=77) vs. 1.0 [1.0-1.0; 1.0-50.0] (n=45) U/mL, respectively;
      P=0.001). CONCLUSIONS: Fecal M2-PK was elevated in children with CF compared with
      HC during infancy and throughout childhood suggesting abnormalities in the CF gut
      exist in early life.

PMID- 28754329
TI  - Inhibition of UDP-glucuronosyltransferase (UGT)-mediated glycyrrhetinic acid 3-O
      glucuronidation by polyphenols and triterpenoids.
AB  - Glycyrrhetinic acid (GA) is an active metabolite of glycyrrhizin, which is a main
      constituent in licorice (Glycyrrhiza glabra). While GA exhibits a wide variety of
      pharmacological activities in the body, it is converted to a toxic metabolite GA
      3-O-glucuronide by hepatic UDP-glucuronosyltransferases (UGTs). To avoid the
      development of the toxic metabolite-induced pseudohyperaldosteronism
      (pseudoaldosteronism), there is a limitation in maximum daily dosage of licorice
      and in combined usage of other glycyrrhizin-containing natural medicine. In this
      study, we investigated the inhibitory effects of various polyphenols and
      triterpenoids on the UGT-mediated GA 3-O-glucuronidation. In human liver
      microsomes, UGT-mediated GA glucuronidation was significantly inhibited by
      protopanaxadiol with an IC50 value of 59.2 MUM. Isoliquiritigenin, rosmarinic
      acid, alisol B, alisol acetate, and catechin moderately inhibited the GA
      glucuronidation with IC50 values of 96.4 MUM, 125 MUM, 160 MUM, 163 MUM, and 164
      MUM. Other tested 19 polyphenols and triterpenoids, including liquiritigenin, did
      not inhibit UGT-mediated GA glucuronidation in human liver microsomes. Our data
      indicate that relatively higher dosage of licorice can be used without a risk of
      developing pseudohyperaldosteronism in combination of natural medicine containing
      protopanaxadiol such as Panax ginseng. Furthermore, supplemental protopanaxadiol
      and isoliquiritigenin might be useful in preventing licorice-inducing
      pseudoaldosteronism.

PMID- 28754330
TI  - Bacterial infection increases risk of carcinogenesis by targeting mitochondria.
AB  - As up to a fifth of all cancers worldwide, have now been linked to microbial
      infections, it is essential to understand the carcinogenic nature of the
      bacterial/host interaction. This paper reviews the bacterial targeting of
      mediators of mitochondrial genomic fidelity and of mitochondrial apoptotic
      pathways, and compares the impact of the bacterial alteration of mitochondrial
      function to that of cancer. Bacterial virulence factors have been demonstrated to
      induce mutations of mitochondrial DNA (mtDNA) and to modulate DNA repair pathways
      of the mitochondria. Furthermore, virulence factors can induce or impair the
      intrinsic apoptotic pathway. The effect of bacterial targeting of mitochondria is
      analogous to behavior of mitochondria in a wide array of tumours, and this
      strongly suggests that mitochondrial targeting of bacteria is a risk factor for
      carcinogenesis.

PMID- 28754331
TI  - Response to the letter to the editor: Mortality risk of elevated alkaline
      phosphatase in patients with coronary artery disease and percutaneous coronary
      intervention.

PMID- 28754332
TI  - Mortality risk of elevated alkaline phosphatase in patients with coronary artery
      disease and percutaneous coronary intervention.

PMID- 28754334
TI  - Antipsychotics and Cerebrovascular Accidents: Taking or Not the Risk?

PMID- 28754333
TI  - Effect of allopurinol and uric acid normalization on serum lipids hyperuricemic
      subjects: A systematic review with meta-analysis.
AB  - Although uric acid is not part of any definition of metabolic syndrome, a number
      of studies have shown strong associations between the concentration of uric acid
      and metabolic syndrome or its components. The purpose of this systematic review
      with meta-analysis was to evaluate, using prospective interventional studies, the
      effects of allopurinol therapy and uric acid normalization on serum
      concentrations of triacylglycerol, total-cholesterol, LDL-cholesterol and HDL
      cholesterol in hyperuricemic subjects. A systematic search of the PubMed and
      Scopus databases was performed following the guidelines described in the PRISMA
      statement. Seven studies were included in the meta-analysis, including six
      randomized controlled trials and one controlled before-and-after study. Despite
      differences in the follow-up periods (4, 12 and 24weeks) and allopurinol dose
      (100-300mg/day), all the studies showed decreases in the mean serum uric acid
      level (95% confidence interval: -2.61 to -1.55 (4weeks), -2.94 to -1.09 (12weeks)
      and -2.59 to -1.22 (24weeks); p<0.05). However, no effect was observed based on
      differences in mean serum triacylglycerol and total- and LDL-cholesterol
      concentrations, independent of the follow-up period. Allopurinol therapy during
      weeks 4 and 12 induced a decrease in the mean HDL-cholesterol level (95%
      confidence interval: -7.22 to -0.47 (4weeks) and -7.18 to -0.32 (12weeks);
      p<0.05). This review suggests that allopurinol and uric acid normalization does
      not improve serum lipid levels, although larger and longer trials of higher
      quality are needed to confirm this.

PMID- 28754335
TI  - Reliability assessment of measuring active wrist pronation and supination range
      of motion with a smartphone.
AB  - This study aimed to improve clinical examination techniques by determining the
      reliability of different methods to evaluate forearm movements. Two methods using
      the iPhoneTM 5 and its gyroscope application (alone [I5] or attached to a selfie
      stick [ISS]) were compared with two conventional measurement devices (a plastic
      goniometer with a hand-held pencil [HHP] and a bubble goniometer [BG]) to
      evaluate the active range of movement (AROM) of the wrist during pronation and
      supination. Two independent groups of subjects took part in this prospective
      single-center diagnostic study: 20 healthy subjects and 20 patients. The four
      evaluation methods had high intra-observer consistency after three measurements
      (intra-class correlation coefficient [ICC] [3, 1] of 0.916 for the HHP; 0.944 for
      ISS; 0.925 for BG; 0.933 for I5) and excellent inter-observer reliability (ICC
      [2, k] of 0.926 for HHP; 0.934 for ISS; 0.899 for BG; 0.894 for I5), with an
      agreement of plus or minus 2 degrees . When these devices are used with rigorous
      methodology, they are reliable for the goniometric evaluation of AROM of wrist
      pronation and supination.

PMID- 28754336
TI  - Unilateral laterothoracic exanthema.

PMID- 28754337
TI  - Kidney disease in pregnant patients.

PMID- 28754338
TI  - Unexpected diagnosis of renal cell carcinoma after thyroid nodule study.

PMID- 28754339
TI  - IL-1 Receptor-Knockout Mice Develop Epidermal Cysts and Show an Altered Innate
      Immune Response after Exposure to UVB Radiation.
AB  - In this study, we observed that mice lacking the IL-1 receptor (IL-1R) (IL1r-/-)
      or deficient in IL1-beta developed multiple epidermal cysts after chronic UVB
      exposure. Cysts that developed in IL1r-/- mice were characterized by the presence
      of the hair follicle marker Sox 9, keratins 10 and 14, and normal melanocyte
      distribution and retinoid X receptor-alpha expression. The increased incidence of
      cysts in IL1r-/- mice was associated with less skin inflammation as characterized
      by decreased recruitment of macrophages, and their skin also maintained epidermal
      barrier function compared with wild-type mice. Transcriptional analysis of the
      skin of IL1r-/- mice after UVB exposure showed decreased gene expression of
      proinflammatory cytokines such as tumor necrosis factor-alpha and IL-6. In vitro,
      primary keratinocytes derived from IL1r-/- mice were more resistant to UVB
      triggered cell death compared with wild-type cells, and tumor necrosis factor
      alpha release was completely blocked in the absence of IL-1R. These observations
      illustrate an unexpected yet prominent phenotype associated with the lack of IL
      1R signaling in mice and support further investigation into the role of IL-1
      ligands in epidermal repair and innate immune response after damaging UVB
      exposure.

PMID- 28754340
TI  - [Is there any relation between couple violence and repeated medical abortion?]
AB  - OBJECTIVES: Risk factors of repeated induced abortion remain unclear. One of them
      could be domestic violence. The aim of this study was to explore the association
      between repeated induced abortion and domestic violence, including violence
      during childhood. MATERIALS AND METHODS: A cross-sectional questionnaire study
      was conducted in three hospitals in Alsace. All women between 18 and 50 years old
      were asked to complete an anonymous questionnaire during their hospitalization
      for induced abortion between 31th of November 2013 and 1st of December 2014. The
      questionnaire included questions about the current or past existence of domestic
      violence. They have also been questioned about the past existence of domestic
      violence between their parents and the fact that they had themselves been victims
      of violence and abuse during childhood. RESULTS: Four hundred and eighty women
      answered to the questionnaire: 322 came for their first abortion while 158 were
      hospitalized for at least the second time for an induced abortion. The proportion
      of current or past violence was 53% in the "repeated induced abortions" group
      compared with 33% in the "first induced abortion" group (OR 2.1, CI 95% [1.4
      3.1], P<0.01). Statistically significant differences were found between the two
      groups for all types of domestic violence. CONCLUSION: In our sample of women, we
      found that experiencing domestic violence with current partner appeared to be a
      risk factor of repeated induced abortions.

PMID- 28754341
TI  - [Exposure to nitrogen dioxide and respiratory health at 2 years in the INMA
      Valencia cohort].
AB  - OBJECTIVE: To analyze the association between exposure to nitrogen dioxide (NO2)
      during pregnancy and the postnatal period up to the age of 2 years old and the
      incidence of respiratory problems in children from the INMA-Valencia cohort.
      METHODS: The study population included 624 children from the INMA-Valencia
      cohort. Individual exposure to NO2 was estimated in different environments
      outside the home during pregnancy and up to the age of 2 using empirical
      measurement and data from geo-statistical methods. Respiratory symptoms were
      obtained from a questionnaire applied at the age of two. The association between
      NO2 exposure and respiratory symptoms was performed using multivariate logistic
      regression. RESULTS: The cumulative incidence was 16.3% for persistent cough,
      34.9% for wheezing and 27.6% for lower respiratory tract infections. No
      association was found between respiratory symptoms and exposure to NO2 in any of
      the children. However an association between NO2 exposure and persistent cough
      was found at two years of life in the children with a parental history of
      allergy. CONCLUSION: NO2 exposure would lead to persistent cough in children with
      a parental history of allergies.

PMID- 28754343
TI  - Evidence-based guidelines for the use of tracheostomy in critically ill patients:
      The role of bronchoscopy.

PMID- 28754344
TI  - The effect of childhood trauma on serum BDNF in bipolar depression is modulated
      by the serotonin promoter genotype.
AB  - In healthy humans, both childhood trauma and the short form of the serotonin
      promoter transporter genotype (5-HTTLPR) are associated with lower levels of
      brain-derived neurotrophic factor (BDNF). In subjects with bipolar disorder (BD),
      lower levels of BDNF and a higher degree of childhood trauma were observed
      compared with healthy controls. However, is still unknown if the functional 5
      HTTLPR polymorphisms exerts an effect on both abnormalities. In 40 inpatients
      affected by a major depressive episode in the course of BD, we genotyped 5
      HTTLPR, measured serum BDNF with ELISA, and assessed early adversities by the
      childhood trauma questionnaire (CTQ). Data were analyzed in the context of the
      general linear model correcting for age, sex, ongoing lithium treatment, severity
      of current depression, and CTQ minimization/denial scores to investigate the
      effect of 5-HTTLPR polymorphism and childhood trauma on BDNF levels. Early trauma
      were negatively associated with BDNF serum levels (higher CTQ scores, lower BDNF;
      p=0.0019). 5-HTTLPR l/l homozygotes showed significantly higher BDNF levels than
      5-HTTLPR*s carriers (30.57+/-6.13 vs 26.82+/-6.41; p=0.0309). A separate-slopes
      analysis showed that 5-HTTLPR significantly influenced the relationship between
      early trauma and adult BDNF (interaction of 5-HTTLPR with CTQ scores: p=0.0023),
      due to a significant relationship between trauma and BDNF in 5-HTTLPR*s carriers,
      but not among l/l homozygotes. Putatively detrimental effects of childhood trauma
      exposure on adult BDNF serum levels are influenced by 5-HTTLPR genotype in
      patients affected by BD. Possible mechanisms include epigenetic modulation of
      BDNF gene expression, due to different reactivity to stressors in 5-HTTLPR
      genotype groups.

PMID- 28754342
TI  - Intramolecular signaling in a cardiac connexin: Role of cytoplasmic domain
      dimerization.
AB  - Gap junctions, composed of connexins, mediate electrical coupling and impulse
      propagation in the working myocardium. In the human heart, the spatio-temporal
      regulation and distinct functional properties of the three dominant connexins
      (Cx43, Cx45, and Cx40) suggests non-redundant physiological roles for each
      isoform. There are substantial differences in gating properties, expression, and
      trafficking among these isoforms, however, little is known about the determinants
      of these different phenotypes. To gain insight regarding these determinants, we
      focused on the carboxyl-terminal (CT) domain because of its importance in channel
      regulation and large degree of sequence divergence among connexin family members.
      Using in vitro biophysical experiments, we identified a structural feature unique
      to Cx45: high affinity (KD~100nM) dimerization between CT domains. In this study,
      we sought to determine if this dimerization occurs in cells and to identify the
      biological significance of the dimerization. Using a bimolecular fluorescence
      complementation assay, we demonstrate that the CT domains dimerize at the plasma
      membrane. By inhibiting CT dimerization with a mutant construct, we show that CT
      dimerization is necessary for proper Cx45 membrane localization, turnover,
      phosphorylation status, and binding to protein partners. Furthermore, CT
      dimerization is needed for normal intercellular communication and hemichannel
      activity. Altogether, our results demonstrate that CT dimerization is a
      structural feature important for correct Cx45 function. This study is significant
      because discovery of how interactions mediated by the CT domains can be modulated
      would open the door to strategies to ameliorate the pathological effects of
      altered connexin regulation in the failing heart.

PMID- 28754345
TI  - Ross River virus disease clinical presentation, pathogenesis and current
      therapeutic strategies.
AB  - Ross River virus (RRV) is an arthitogenic alphavirus capable of causing outbreaks
      of debilitating musculoskeletal inflammatory disease in humans. RRV is the most
      common mosquito-borne disease in Australia, with outbreaks of RRV generally
      occurring during seasonal wet and warm conditions. Patients with Ross River virus
      disease (RRVD) typically present with fever, polyarthralgia, myalgia and a
      maculopapular erythematous rash. Treatment of the disease is usually palliative
      with no licensed vaccines or antiviral therapies currently available. In an
      effort to better inform therapeutic design, much progress has been made to
      understand the pathogenesis of RRVD. Progress has been largely driven by clinical
      evaluations supported by research using established murine models of RRVD, able
      to accurately replicate human disease. In this review we describe RRVD
      pathogenesis and the role of the host immune response, with particular focus on
      insights from studying animal models. We also discuss prospects for effective
      vaccines, preclinical development of therapeutic strategies and raise important
      questions for future RRV research.

PMID- 28754346
TI  - Characterization of two peptides isolated from the venom of social wasp
      Chartergellus communis (Hymenoptera: Vespidae): Influence of multiple alanine
      residues and C-terminal amidation on biological effects.
AB  - Chatergellus communis is a wasp species endemic to the neotropical region and its
      venom constituents have never been described. In this study, two peptides from C.
      communis venom, denominated Communis and Communis-AAAA, were chemically and
      biologically characterized. In respect to the chemical characterization, the
      following amino acid sequences and molecular masses were identified: Communis:
      Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-COOH (1340.9Da) Communis-AAAA:
      Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-Ala-Ala-Ala-Ala-Val-Xle-NH2
      (1836.3Da). Furthermore, their biological effects were compared, accounting for
      the differences in structural characteristics between the two peptides. To this
      end, three biological assays were performed in order to evaluate the
      hyperalgesic, edematogenic and hemolytic effects of these molecules. Communis
      AAAA, unlike Communis, showed a potent hemolytic activity with EC50=142.6MUM.
      Moreover, the highest dose of Communis-AAAA (2nmol/animal) induced hyperalgesia
      in mice. On the other hand, Communis (10nmol/animal) was able to induce edema but
      did not present hemolytic or hyperalgesic activity. Although both peptides have
      similarities in linear structures, we demonstrated the distinct biological
      effects of Communis and Communis-AAAA. This is the first study with Chartegellus
      communis venom, and both Communis and Communis-AAAA are unpublished peptides.

PMID- 28754347
TI  - Inhibitory action of tongue sole LPXRFa, the piscine ortholog of gonadotropin
      inhibitory hormone, on the signaling pathway induced by tongue sole kisspeptin in
      COS-7 cells transfected with their cognate receptors.
AB  - Kisspeptin (Kiss) acts as a positive regulator of reproduction by acting on
      gonadotropes and gonadotropin-releasing hormone (GnRH) neurons. Despite its
      functional significance, the intricate web of intracellular signal transduction
      pathways in response to Kiss is still far from being fully understood in
      teleosts. Accordingly, we investigated the molecular mechanism of Kiss action and
      its possible interaction with LPXRFa signaling in this study. In vitro functional
      analysis revealed that synthetic tongue sole Kiss2 decapeptide increased the cAMP
      responsive element-dependent luciferase (CRE-luc) activity in COS-7 cells
      transfected with its cognate receptor, while this stimulatory effect was markedly
      reduced by two inhibitors of the adenylate cyclase (AC)/protein kinase A (PKA)
      pathway. Similarly, Kiss2 also significantly stimulated serum responsive element
      dependent luciferase (SRE-luc) activity, whereas this stimulatory effect was
      evidently attenuated by two inhibitors of the phospholipase C (PLC)/protein
      kinase C (PKC) pathway. In addition, LPXRFa-2 suppressed Kiss2-elicited CRE-luc
      activity in a dose-dependent manner. Taken together, Kiss2 utilizes both AC/PKA
      and PLC/PKC pathways to exert its functions via its cognate receptor and LPXRFa
      may antagonize the action of Kiss2 by inhibiting kisspeptin signaling. As far as
      we know, this study is the first to characterize the half-smooth tongue sole
      kisspeptin and LPXRFa signaling pathway in COS-7 cells transfected with their
      cognate receptors and provides novel information on the interaction between
      LPXRFa system and kisspeptin system in teleosts.

PMID- 28754349
TI  - Effect of steviol, steviol glycosides and stevia extract on glucocorticoid
      receptor signaling in normal and cancer blood cells.
AB  - The use of steviol glycosides as non-caloric sweeteners has proven to be
      beneficial for patients with type 2 diabetes mellitus (T2D), obesity, and
      metabolic syndrome. However, recent data demonstrate that steviol and stevioside
      might act as glucocorticoid receptor (GR) agonists and thus correlate with
      adverse effects on metabolism. Herein, we evaluated the impact of steviol,
      steviol glycosides, and a Greek-derived stevia extract on a number of key steps
      of GR signaling cascade in peripheral blood mononuclear cells (PBMCs) and in
      Jurkat leukemia cells. Our results revealed that none of the tested compounds
      altered the expression of primary GR-target genes (GILZ, FKPB5), GR protein
      levels or GR subcellular localization in PBMCs; those compounds increased GILZ
      and FKPB5 mRNA levels as well as GRE-mediated luciferase activity, inducing in
      parallel GR nuclear translocation in Jurkat cells. The GR-modulatory activity
      demonstrated by stevia-compounds in Jurkat cells but not in PBMCs may be due to a
      cell-type specific effect.

PMID- 28754348
TI  - Neural correlates of familial obesity risk and overweight in adolescence.
AB  - BACKGROUND: Rates of adolescent obesity and overweight are high. The offspring of
      overweight parents are at increased risk of becoming obese later in life.
      Investigating neural correlates of familial obesity risk and current overweight
      status in adolescence could help identify biomarkers that predict future obesity
      and that may serve as novel targets for obesity interventions. OBJECTIVE: Our
      primary aim was to use functional MRI to compare neural responses to words
      denoting high or low energy density (ED) foods and non-foods, in currently lean
      adolescents at higher compared with lower familial risk for obesity, and in
      overweight compared with lean adolescents. Secondary aims were to assess group
      differences in subjective appetite when viewing food and non-food words, and in
      objective ad libitum intake of high-ED foods in a laboratory setting. DESIGN: We
      recruited 36 adolescents (14-19y), of whom 10 were (obese/overweight
      "overweight"), 16 lean with obese/overweight mothers (lean high-risk, "lean-HR"),
      and 10 lean with lean mothers (lean low-risk, "lean-LR"). All underwent fMRI
      scanning while they viewed words representing high-ED foods, low-ED foods, or non
      foods, and provided appetitive ratings in response to each word stimulus. They
      then consumed a multi-item ad libitum buffet meal. RESULTS: Food compared with
      non-food words activated a distributed emotion/reward system including insula and
      pregenual anterior cingulate cortex (ACC). Participants who were at increasing
      risk for obesity exhibited progressively weaker activation of an
      attentional/regulatory system including dorsolateral prefrontal cortex (PFC),
      dorsal ACC, and basal ganglia nuclei (activation was greatest in lean-LR,
      intermediate in lean-HR, and weakest in the overweight group). These group
      differences were most apparent for neural responses to high-compared with low-ED
      foods. Lean-HR (compared with lean-LR and overweight) adolescents reported
      greater desire for high-ED foods. Meal intake was greatest for the overweight,
      then lean-HR, then lean-LR groups. CONCLUSIONS: Adolescents at higher obesity
      risk exhibited reduced neural responses to high-ED food cues in a neural system
      that subserves attention and self-regulation. They also reported heightened
      appetitive responses to high-ED cues. Interventions that promote the capacity for
      self-regulation could prevent youth who have a familial predisposition for
      obesity from translating risk into reality.

PMID- 28754350
TI  - Beneficial metabolic effects of dietary epigallocatechin gallate alone and in
      combination with exendin-4 in high fat diabetic mice.
AB  - OBJECTIVE: Significant attempts are being made to generate multifunctional,
      hybrid or peptide combinations as novel therapeutic strategies for type 2
      diabetes, however this presents key challenges including design and
      pharmaceutical development. In this study, we evaluated metabolic properties of
      oral nutritional supplement epigallocatechin gallate (EGCG) in combination with
      GLP-1 agonist exendin-4 in a mouse model of dietary-induced diabetes and obesity.
      METHODS: EGCG, exendin-4 or combination of both were administered twice-daily
      over 28 days to high fat (HF) mice on background of low-dose streptozotocin.
      Energy intake, body weight, fat mass, glucose tolerance, insulin sensitivity,
      lipid profile, biochemical and hormone markers, and islet histology were
      examined. RESULTS: All treatment groups exhibited significantly reduced body
      weight, fat mass, circulating glucose and insulin concentrations, and HbA1c
      levels which were independent of changes in energy intake. Similarly, there was
      marked improvement in glycaemic control, glucose-stimulated insulin release,
      insulin sensitivity, total cholesterol and triglycerides, with most prominent
      effects observed following combination therapy. Circulating corticosterone
      concentrations and 11beta-hydroxysteroid dehydrogenase type1 (11beta-HSD1)
      staining (in pancreas) were beneficially decreased without changes in circulating
      interleukin 6 (IL-6), alanine transaminase (ALT) and glutathione reductase.
      Combination therapy resulted in increased islet area and number, beta cell area,
      and pancreatic insulin content. Generally, metabolic effects were much more
      pronounced in mice which received combination therapy. CONCLUSIONS: EGCG alone
      and particularly in combination with exendin-4 exerts positive metabolic
      properties in HF mice. EGCG may be useful dietary adjunct alongside GLP-1
      mimetics in treatment of diabetes and related disorders.

PMID- 28754351
TI  - The alpha-7 nicotinic acetylcholine receptor is involved in a direct inhibitory
      effect of nicotine on GnRH release: In vitro studies.
AB  - The activation of nicotinic cholinergic receptors (nAChR) inhibits the
      reproductive axis; however, it is not clear whether nicotine may directly
      modulate the release of hypothalamic gonadotropin-releasing hormone (GnRH).
      Experiments carried out in GT1-1 immortalized GnRH neurons reveal the presence of
      a single class of high affinity alpha4beta2 and alpha7 nAchR subtypes. The
      exposure of GT1-1 cells to nicotine does not modify the basal accumulation of
      GnRH. However, nicotine was found to modify GnRH pulsatility in perifusion
      experiments and inhibits, the release of GnRH induced by prostaglandin E1 or by
      K+-induced cell depolarization; these effects were reversed by D-tubocurarine and
      alpha-bungarotoxin. In conclusion, the results reported here indicate that:
      functional nAChRs are present on GT1-1 cells, the activation of the alpha
      bungarotoxin-sensitive subclass (alpha7) produces an inhibitory effect on the
      release of GnRH and that the direct action of nicotine on GnRH neurons may be
      involved in reducing fertility of smokers.

PMID- 28754352
TI  - 3-Iodothyronamine reduces insulin secretion in vitro via a mitochondrial
      mechanism.
AB  - PURPOSE: 3-iodothyronamine (3-T1AM), a decarboxylated and deiodinated thyroid
      hormone metabolite, leads at pharmacological doses to hypoinsulinemia,
      hyperglucagonemia and hyperglycemia in vivo. As the pancreatic Langerhans islets
      express thyroid hormone transmembrane transporters (THTT), we tested the
      hypothesis that not only plasma membrane-mediated 3-T1AM binding to and
      activation of G-protein coupled receptors, but also 3-T1AM metabolite(s)
      generated by 3-T1AM uptake and metabolism might decrease glucose-stimulated
      insulin secretion (GSIS). METHODS: Murine pancreatic beta-cells MIN6 were
      characterized for gene expression of THTT, deiodinases and monoamine oxidases. 3
      T1AM uptake and intracellular metabolism to the corresponding 3-iodothyroacetic
      acid were analysed by liquid-chromatography tandem mass spectrometry (LC-MS/MS)
      at different time points in cells as well as the conditioned medium.
      Mitochondrial activity, especially ATP-production, was monitored real-time after
      3-T1AM application using Seahorse Bioanalyzer technique. Effect of 3-T1AM on GSIS
      into the culture medium was assayed by ELISA. RESULTS: MIN6 cells express
      classical THTT, proposed to transport 3-T1AM, as well as 3-T1AM metabolizing
      enzymes comparable to murine primary pancreatic islets. 3-T1AM accumulates in
      MIN6 cells and is metabolized by intracellular MaoB to 3-iodothyroacetic, which
      in turn is rapidly exported. 3-T1AM decreases mitochondrial ATP-production
      concentration dependently. GSIS is diminished by 3-T1AM treatment. Using LC
      MS/MS, no further 3-T1AM metabolites except 3-iodothyroacetic were detectable.
      CONCLUSIONS: This data provides a first link between cellular 3-T1AM uptake and
      regulation of mitochondrial energy metabolism in beta-cells, resulting in reduced
      insulin secretion. We conclude that MIN6 is an appropriate cell model to study 3
      T1AM-dependent (intra-)cellular biochemical mechanisms affecting insulin
      production in vitro.

PMID- 28754353
TI  - "Futile Care"-An Emergency Medicine Approach: Ethical and Legal Considerations.
AB  - Futility often serves as a proposed reason for withholding or withdrawing medical
      treatment, even in the face of patient and family requests. Although there is
      substantial literature describing the meaning and use of futility, little of it
      is specific to emergency medicine. Furthermore, the literature does not provide a
      widely accepted definition of futility, and thus is difficult if not impossible
      to apply. Some argue that even a clear concept of futility would be inappropriate
      to use. This article will review the origins of and meanings suggested for
      futility, specific challenges such cases create in the emergency department (ED),
      and the relevant legal background. It will then propose an approach to cases of
      perceived futility that is applicable in the ED and does not rely on unilateral
      decisions to withhold treatment, but rather on avoiding and resolving the
      conflicts that lead to physicians' believing that patients are asking them to
      provide "futile" care.

PMID- 28754354
TI  - Bolus-Dose Vasopressors in the Emergency Department: First, Do No Harm; Second,
      More Evidence Is Needed.

PMID- 28754355
TI  - Managing Patients With Transient Ischemic Attack.

PMID- 28754356
TI  - Does the Use of Video Laryngoscopy Improve Intubation Outcomes?

PMID- 28754357
TI  - What Is the Utility of End-Tidal Capnography for Procedural Sedation and
      Analgesia in the Emergency Department?

PMID- 28754358
TI  - Provider and Practice Factors Associated With Emergency Physicians' Being Named
      in a Malpractice Claim.
AB  - STUDY OBJECTIVE: We examine the association between emergency physician
      characteristics and practice factors with the risk of being named in a
      malpractice claim. METHODS: We used malpractice claims along with provider,
      operational, and jurisdictional data from a national emergency medicine group (87
      emergency departments [EDs] in 15 states from January 1, 2010, to June 30, 2014)
      to assess the relationship between individual physician and practice variables
      and being named in a malpractice claim. Individual and practice factors included
      years in practice, emergency medicine board certification, visit admission rate,
      relative value units generated per hour, total patients treated as attending
      physician of record, working at multiple facilities, working primarily overnight
      shifts, patient experience data percentile, and state malpractice environment. We
      assessed the relationship between emergency physician and practice variables and
      malpractice claims, using logistic regression. RESULTS: Of 9,477,150 ED visits
      involving 1,029 emergency physicians, there were 98 malpractice claims against 90
      physicians (9%). Increasing total number of years in practice (adjusted odds
      ratio 1.04; 95% confidence interval 1.02 to 1.06) and higher visit volume
      (adjusted odds ratio 1.09 per 1,000 visits; 95% confidence interval 1.05 to 1.12)
      were associated with being named in a malpractice claim. No other factors were
      associated with malpractice claims. CONCLUSION: In this sample of emergency
      physicians, 1 in 11 were named in a malpractice claim during 4.5 years. Total
      number of years in practice and visit volume were the only identified factors
      associated with being named, suggesting that exposure to higher patient volumes
      and longer practice experience are the primary contributors to malpractice risk.

PMID- 28754359
TI  - The (Continued) Challenges of Out-of-Hospital Rapid Sequence Intubation.

PMID- 28754360
TI  - Glycosylation flux analysis reveals dynamic changes of intracellular
      glycosylation flux distribution in Chinese hamster ovary fed-batch cultures.
AB  - N-linked glycosylation of proteins has both functional and structural
      significance. Importantly, the glycan structure of a therapeutic protein
      influences its efficacy, pharmacokinetics, pharmacodynamics and immunogenicity.
      In this work, we developed glycosylation flux analysis (GFA) for predicting
      intracellular production and consumption rates (fluxes) of glycoforms, and
      applied this analysis to CHO fed-batch immunoglobulin G (IgG) production using
      two different media compositions, with and without additional manganese feeding.
      The GFA is based on a constraint-based modeling of the glycosylation network,
      employing a pseudo steady state assumption. While the glycosylation fluxes in the
      network are balanced at each time point, the GFA allows the fluxes to vary with
      time by way of two scaling factors: (1) an enzyme-specific factor that captures
      the temporal changes among glycosylation reactions catalysed by the same enzyme,
      and (2) the cell specific productivity factor that accounts for the dynamic
      changes in the IgG production rate. The GFA of the CHO fed-batch cultivations
      showed that regardless of the media composition, galactosylation fluxes decreased
      with the cultivation time more significantly than the other glycosylation
      reactions. Furthermore, the GFA showed that the addition of Mn, a cofactor of
      galactosyltransferase, has the effect of increasing the galactosylation fluxes
      but only during the beginning of the cultivation period. The results thus
      demonstrated the power of the GFA in delineating the dynamic alterations of the
      glycosylation fluxes by local (enzyme-specific) and global (cell specific
      productivity) factors.

PMID- 28754361
TI  - Descending thoracic aortic mural thrombus presentation and treatment strategies.
AB  - BACKGROUND: Thoracic aortic mural thrombus (TAMT) of the descending aorta is rare
      but can result in dramatic embolic events. Early treatment is therefore crucial;
      however, there is not a consensus on ideal initial treatment. METHODS: A review
      of the literature using PubMed was conducted, and all relevant publications
      describing descending TAMT of the past 15 years were reviewed. Variables included
      for this analysis were presentation, initial treatment strategy employed, outcome
      measures of thrombus resolution or regression, recurrence of symptomatic emboli,
      and mortality. RESULTS: Seventy-four patients were included in this analysis.
      Women were significantly more likely to be described with descending TAMT. The
      majority (82.4%) of cases reported were diagnosed after an embolic event.
      Patients were equally likely to receive medical, open surgical, or endovascular
      therapy as the initial treatment modality. However, there is a trend within the
      past 5 years to report cases describing successful thoracic endovascular aortic
      repair for initial management. Of patients who initially underwent medical
      management, nine patients (34.6%) had persistent thrombus. Of the patients who
      initially underwent open surgical repair, six patients (31.6%) had persistent
      thrombus; of these patients, four underwent endovascular repair. Twenty-nine
      patients (39.2%) with descending TAMT initially underwent thoracic endovascular
      aortic repair. Twenty-seven (93.1%) had fully excluded thrombus at the time of
      the procedure, with no recurrence or evidence of repeated embolic phenomena at
      follow-up. CONCLUSIONS: Whereas mural thrombus of the thoracic aorta is uncommon,
      it must be considered in the differential diagnosis of embolic events. Although
      endovascular therapy may be a useful first-line option for TAMT with reports of
      positive outcomes in select literature, further study of this treatment option is
      required.

PMID- 28754362
TI  - Design, synthesis and biological evaluation of indole derivatives as Vif
      inhibitors.
AB  - The crystal structure of viral infectivity factor (Vif) was reported recently,
      which makes it possible to design new inhibitors against Vif by structure-based
      drug design. Through analysis of the protein surface of Vif, the C2 pocket
      located in the N-terminal was found, which is suit for developing small molecular
      inhibitors. Then, in our article, fragment-based virtual screening (FBVS) was
      conducted and a series of fragments was obtained, among which, Zif-1 bearing
      indole scaffold and pyridine ring can form H-bonds with Tyr148 and Ile155.
      Subsequently, 19 derivatives of Zif-1 were synthesized. Through the immune
      fluorescence staining and Western blot assays, Zif-15 shows potent activity in
      inhibiting Vif-mediated A3G degradation. Further docking experiment shows that
      Zif-15 form H-bond interactions with residues His139, Tyr148 and Ile155.
      Therefore, Zif-15 is a promising lead compound against Vif that can be used to
      treat AIDS.

PMID- 28754363
TI  - Discovery of orally bioavailable cyclohexanol-based NR2B-selective NMDA receptor
      antagonists with analgesic activity utilizing a scaffold hopping approach.
AB  - NR2B subunit containing N-methyl-d-aspartate (NMDA) receptor is an attractive
      target for chronic pain due to its involvement in disease states and its limited
      distribution in the central nervous system. Cyclohexanol-based leads 6a and 6c
      were identified as potent NR2B-selective NMDA antagonists utilizing a scaffold
      hopping approach. Further optimization of this series through replacement of the
      amide in the leads with an isoxazole and efforts to optimize the pharmacokinetic
      profiles led to the discovery of orally available brain penetrants 7k and 7l,
      which demonstrated analgesic activity in the mouse formalin test at early and
      late phases.

PMID- 28754364
TI  - Syntheses of cytotoxic novel arctigenin derivatives bearing halogen and alkyl
      groups on aromatic rings.
AB  - The new lignano-9,9'-lactones (alpha,beta-dibenzyl-gamma-butyrolactone lignans),
      which showed the higher cytotoxicity than arctigenin, were synthesized. The well
      known cytotoxic arctigenin showed activity against HL-60 cells (EC50=12MUM),
      however, it was inactive against HeLa cells (EC50>100MUM). The synthesized (3,4
      dichloro, 2'-butoxy)-derivative 55 and (3,4-dichloro, 4'-butyl)-derivative 66
      bearing the lignano-9,9'-lactone structures showed the EC50 values of 10MUM and
      9.4MUM against HL-60 cells, respectively. Against HeLa cells, the EC50 value of
      the derivative 66 was 27MUM. By comparing the activities with the corresponding
      9,9'-epoxy structure (tetrahydrofuran compounds), the importance of the lactone
      structure of 55 and 66 for the higher activities was shown. The substituents on
      the aromatic ring of the lignano-9,9'-lactones affected the cytotoxicity level,
      observing more than 10-fold difference.

PMID- 28754365
TI  - Change in lip closing force in Classes II and III malocclusion before and after
      sagittal split ramus osteotomy with Le Fort I osteotomy.
AB  - PURPOSE: The purpose of this study was to examine lip closing force in Class II
      and III patients before and after orthognathic surgery. SUBJECT AND METHODS: The
      subjects were 45 patients (15 Class II women, 15 Class III men and 15 Class III
      women) diagnosed with jaw deformity who underwent sagittal split ramus osteotomy
      with Le Fort I osteotomy and 30 controls with normal skeleton and occlusion (15
      men, 15 women). Maximum and minimum lip closing forces were measured using Lip De
      Cum(r) before and after surgery, and compared statistically. RESULTS: In the
      Class II women, maximum and minimum lip closing forces did not change after
      surgery. However, maximum and minimum lip pressure increased significantly in the
      Class III men (P = 0.0116, P = 0.0295) and maximum lip closing force increased
      significantly in the Class III women (P = 0.0082). After 6 months, maximum lip
      closing force was significantly lower in both Classes II and III women than in
      the control women (P = 0.0002, P = 0.0045). CONCLUSIONS: This study suggested
      that maximum postoperative lip pressure did not improve in the Class II women,
      although maximum lip closing force increased in the Class III men and women after
      sagittal split ramus osteotomy with Le Fort I osteotomy.

PMID- 28754366
TI  - Conditional survival in patients with unresectable perihilar cholangiocarcinoma.
AB  - BACKGROUND: Conditional survival is the life expectancy from a point in time for
      a patient who has survived a specific period after presentation. The aim of the
      study was to estimate conditional survival for patients with unresectable
      perihilar cholangiocarcinoma. METHODS: Patients with unresectable perihilar
      cholangiocarcinoma from two academic hospitals in the Netherlands between 2002
      and 2012 were assessed. A multivariable Cox proportional hazards analysis was
      performed to identify risk factors associated with overall survival. Survival was
      estimated using the Kaplan-Meier method to evaluate factors associated with
      overall survival. RESULTS: In total, 572 patients were included. Overall survival
      was 42% at one year and 6% at three years. The conditional chance of surviving
      three years was 15% at 1 year and increased to 38% at 2 years. Independent poor
      prognostic factors for overall survival were age >=65 years, tumor size >3 cm on
      imaging, bilirubin levels (>250 MUmol/L), CA19-9 level at presentation (>1000
      U/ml), and suspected distant metastases on imaging. The conditional survival of
      patients with and without these prognostic factors was comparable after patients
      survived the first two or more years. CONCLUSION: The conditional chance of
      surviving for patients with unresectable perihilar cholangiocarcinoma increases
      with time. Poor prognostic factors become less relevant once patients have
      survived two years.

PMID- 28754367
TI  - Nationwide prospective audit of pancreatic surgery: design, accuracy, and
      outcomes of the Dutch Pancreatic Cancer Audit.
AB  - BACKGROUND: Auditing is an important tool to identify practice variation and
      'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch
      centers for pancreatic surgery. METHODS: Performance indicators and case-mix
      factors were identified by a PubMed search for randomized controlled trials
      (RCT's) and large series in pancreatic surgery. In addition, data dictionaries of
      two national audits, three institutional databases, and the Dutch national cancer
      registry were evaluated. Morbidity, mortality, and length of stay were analyzed
      of all pancreatic resections registered during the first two audit years. Case
      ascertainment was cross-checked with the Dutch healthcare inspectorate and key
      variables validated in all centers. RESULTS: Sixteen RCT's and three large series
      were found. Sixteen indicators and 20 case-mix factors were included in the
      audit. During 2014-2015, 1785 pancreatic resections were registered including
      1345 pancreatoduodenectomies. Overall in-hospital mortality was 3.6%. Following
      pancreatoduodenectomy, mortality was 4.1%, Clavien-Dindo grade >= III morbidity
      was 29.9%, median (IQR) length of stay 12 (9-18) days, and readmission rate
      16.0%. In total 97.2% of >40,000 variables validated were consistent with the
      medical charts. CONCLUSIONS: The Dutch Pancreatic Cancer Audit, with high quality
      data, reports good outcomes of pancreatic surgery on a national level.

PMID- 28754368
TI  - What are the six degree-of-freedom errors of a robotically-machined femoral
      cavity in total hip arthroplasty and are they clinically important? An in-vitro
      study.
AB  - Errors during a robot-assisted THA may result in a femoral cavity with position
      and orientation different than planned. This can lead to a femoral component
      placement that inaccurately sets a patient's femoral anteversion (FA), femoral
      offset (FO), and vertical offset (VO). The objectives of this study were to
      determine the position and orientation errors of robotically-machined femoral
      cavities in six degrees of freedom and to determine how position and orientation
      errors translate into errors in the setting of FA, FO, and VO. After creating
      preoperative plans, robot-assisted THAs were performed on twelve cadaveric
      specimens. The position and orientation of the machined cavities were compared to
      those of the planned cavities to determine the errors in six degrees of freedom.
      Placement of femoral components into the machined cavities was simulated, and the
      differences in FA, FO, and VO between the simulated and planned component
      placement were computed. While bias (i.e. mean error) occurred for three of six
      degrees of freedom in femoral cavities machined by a robotic system, the root
      mean squared errors (RMSEs) when the placement of femoral component was simulated
      were limited to 1.9 degrees  for FA, 1.0mm for FO, and 2.1mm for VO and were
      clinically unimportant.

PMID- 28754369
TI  - Reply.

PMID- 28754370
TI  - Editorial Comment.

PMID- 28754371
TI  - Reply by Authors.

PMID- 28754372
TI  - Endogenous nitric oxide inhibits spinal NMDA receptor activity and pain
      hypersensitivity induced by nerve injury.
AB  - The role of nitric oxide (NO) in nociceptive transmission at the spinal cord
      level remains uncertain. Increased activity of spinal N-methyl-d-aspartate (NMDA)
      receptors contributes to development of chronic pain induced by peripheral nerve
      injury. In this study, we determined how endogenous NO affects NMDA receptor
      activity of spinal cord dorsal horn neurons in control and spinal nerve-ligated
      rats. Bath application of the NO precursor l-arginine or the NO donor S-nitroso-N
      acetylpenicillamine (SNAP) significantly inhibited NMDA receptor currents of
      spinal dorsal horn neurons in both sham control and nerve-injured rats.
      Inhibition of neuronal nitric oxide synthase (nNOS) or blocking the S
      nitrosylation reaction with N-ethylmaleimide abolished the inhibitory effects of
      l-arginine on NMDA receptor currents recorded from spinal dorsal horn neurons in
      sham control and nerve-injured rats. However, bath application of the cGMP analog
      8-bromo-cGMP had no significant effects on spinal NMDA receptor currents.
      Inhibition of soluble guanylyl cyclase also did not alter the inhibitory effect
      of l-arginine on spinal NMDA receptor activity. Furthermore, knockdown of nNOS
      with siRNA abolished the inhibitory effects of l-arginine, but not SNAP, on
      spinal NMDA receptor activity in both groups of rats. Additionally, intrathecal
      injection of l-arginine significantly attenuated mechanical or thermal
      hyperalgesia induced by nerve injury, and the l-arginine effect was diminished in
      rats treated with a nNOS inhibitor or nNOS-specific siRNA. These findings suggest
      that endogenous NO inhibits spinal NMDA receptor activity through S
      nitrosylation. NO derived from nNOS attenuates spinal nociceptive transmission
      and neuropathic pain induced by nerve injury.

PMID- 28754373
TI  - Cannabidiol disrupts the consolidation of specific and generalized fear memories
      via dorsal hippocampus CB1 and CB2 receptors.
AB  - Pharmacological interventions able to modulate a fear memory while it is
      consolidated could have therapeutic value in tempering those maladaptively
      overconsolidated. Animal and human studies have shown the intensity of
      unconditioned stimulus delivered during fear conditioning influences qualitative
      and quantitative aspects of the memory to be established. By varying the shock
      intensity used for contextual pairing in rats, here we induced specific and more
      generalized long-term fear memories to investigate whether, how and where in the
      brain the cannabidiol (CBD; 3.0-30 mg/kg i.p.) could impair their consolidation
      and related outcomes. When given immediately after their acquisition, it reduced
      respectively the conditioned fear expression, and fear generalization, ultrasonic
      vocalizations at 22-kHz and the relative resistance to extinction. CBD had no
      effects on short-term fear memory, and its delayed treatment no longer affected
      the consolidation process. As the dorsal hippocampus (DH) modulates fear memory
      specificity and generalization, and cannabinoid type-1 (CB1) and type-2 (CB2)
      receptors contribute to consolidation, we investigated their involvement in CBD
      effects. Both systemic and intra-DH treatment with the CB1 receptor
      antagonist/inverse agonist AM251 or the CB2 receptor antagonist/inverse agonist
      AM630 prevented the disrupting CBD effects on consolidation. Since the CBD
      effects on the endocannabinoid transmission are probably indirect, we
      investigated and demonstrated the FAAH inhibitor URB597 induced effects similar
      to those of CBD when given systemically or intra-DH. Altogether, the present
      results suggest the CBD disrupts the consolidation of different fear memories via
      anandamide-mediated activation of DH CB1 and CB2 receptors.

PMID- 28754374
TI  - OH1 from Orf Virus: A New Tyrosine Phosphatase that Displays Distinct Structural
      Features and Triple Substrate Specificity.
AB  - Viral tyrosine phosphatases such as VH1 from Vaccinia and Variola virus are
      recognized as important effectors of host-pathogen interactions. While proteins
      sharing sequence to VH1 have been identified in other viruses, their structural
      and functional characterization is not known. In this work, we determined the
      crystal structure of the VH1 homolog in the Orf virus, herein named OH1.
      Similarly to Variola and Vaccinia VH1, the structure of OH1 shows a dimer with
      the typical dual-specificity phosphatase fold. In contrast to VH1, the OH1 dimer
      is covalently stabilized by a disulfide bond involving residue Cys15 in the N
      terminal helix alpha-1 of both monomers, and Cys15 is a conserved residue within
      the Parapoxvirus genus. The in vitro functional characterization confirms that
      OH1 is a dual-specificity phosphatase and reveals its ability to dephosphorylate
      phosphatidylinositol 3,5-bisphosphate, a new activity potentially relevant in
      phosphoinositide recycling during virion maturation.

PMID- 28754375
TI  - An evaluation of myeloperoxidase-mediated bio-activation of NSAIDs in
      promyelocytic leukemia (HL-60) cells for potential cytotoxic selectivity.
AB  - Several lines of evidence have pointed towards the potential therapeutic benefit
      of NSAIDs in cancer therapy. In this study, we have investigated the acute bio
      activation of NSAIDs and their metabolites via myeloperoxidase (MPO), a highly
      expressed peroxidase enzyme in acute myeloid leukemia. As bio-activation involves
      the formation of reactive metabolites, we hypothesized that NSAIDs which produced
      reactive metabolites would be correlated with leukemia cell toxicity. We tested
      the enzymatic peroxidation of three NSAIDs, namely diclofenac, indomethacin, and
      naproxen in comparison with their hepatic metabolites, 4'- hydroxydiclofenac (4'
      OHD), 5-hydroxydiclofenac (5-OHD), O-desmethyl-N-deschlorobenzoylindomethacin
      (DMBI), O-desmethylindomethacin (DMI) and O-desmethylnaproxen (ODN). Firstly, we
      used purified peroxidases in kinetic UV-vis kinetic spectrophotometry, and
      electron paramagnetic resonance (EPR) experiments to determine oxidation of
      ascorbic acid and glutathione (GSH), respectively. We then used HL-60 cells, as a
      model of acute myelogenous leukemia to carry out trypan blue exclusion, cellular
      ATP analysis, mitochondrial membrane potential (MMP) and cytofluorometric GSH
      assays. Our results present evidence that diclofenac, 4'-OHD, 5-OHD, DMBI and DMI
      demonstrated significant cytotoxic effect in the leukemic cells through oxidation
      by intracellular MPO. In the same vein, only diclofenac and its two metabolites
      caused a significant drop in the MMP and cellular ATP level; however, the cell
      death induced by indomethacin metabolites reflected a subtle effect on MMP or GSH
      content. Interestingly, only diclofenac and 4'-OHD (and not 5- OHD) caused a
      significant drop in HL-60 cells' GSH content. Among diclofenac compounds, only 4'
      OHD also generated GS radical and caused a significant increase in ascorbate co
      oxidation rate. Lastly, even though ODN also generated GS radical and potently
      cooxidized ascorbate, it showed no significant cytotoxicity. These results
      provide evidence of a correlation between acute cytotoxicity and MPO-bioactivated
      NSAIDs, though this was not correlated for all compounds (e.g., ODN). Further
      studies are required to determine both the MPO-dependent and MPO-independent
      mechanisms of cytotoxicity.

PMID- 28754376
TI  - Characterization of MXR activity in the sea anemone Bunodosoma cangicum exposed
      to copper.
AB  - Transmembrane proteins of the ABC family contribute to a multiple xenobiotic
      resistance (MXR) phenotype in cells, driving the extrusion of toxic substances.
      This phenotype promotes a high degree of protection against xenobiotics. The
      present study provides a better understanding of the MXR activity in the podal
      disk cells of Bunodosoma cangicum exposed to copper, and further establishes the
      relationship between protein activity (measured by accumulation of rhodamine-B)
      and bioaccumulation of copper in these cells. Sea anemone cells were exposed for
      24h to copper (0, 7.8 and 15.6MUg/L) in presence and absence of MXR blocker
      (verapamil 50MUM). Results indicate that copper exposure increases intracellular
      metal content when ABC proteins were blocked, causing an increase in cellular
      death. The present study also verified the relationship between MXR activity, ATP
      depletion, and general metabolic activity (by MTT). MXR activity decreased in
      treatment groups exposed to copper concentrations of 15.6MUg/L and 10mM energy
      depleting potassium cyanide. Metabolic activity increased in cells exposed to
      7.8MUgCu/L, but 15.6MUgCu/L was similar to 0 and 7.8MUg/L. The presence of copper
      decreased the ABC proteins expression. The present study improves the knowledge
      of MXR in anemone cells and shows that this activity is closely associated with
      copper extrusion. Also, the copper exposure is able to modify the metabolic state
      and to lead to cytotoxicity when cells cannot defend themselves.

PMID- 28754377
TI  - The insufficient integration of medicine into clinical dental education: a missed
      opportunity or an ethical dilemma?

PMID- 28754378
TI  - Chronic fibrosing osteomyelitis of the jaws: an important cause of recalcitrant
      facial pain. A clinicopathologic study of 331 cases in 227 patients.
AB  - OBJECTIVE: This was a retrospective and follow-up analysis of 331 cases of
      chronic fibrosing osteomyelitis of the jaws (CFOJ) in 227 patients. STUDY DESIGN:
      Demographic, clinical, surgical, and microscopic characteristics were tabulated
      for all patients. A follow-up mail survey was used to determine the degree of
      symptom relief experienced after surgery. RESULTS: The female to male ratio
      approached 7:1, and mean age of patients was 53 years. The most common sites were
      the mandibular posterior region, followed by the maxillary posterior region.
      Consistent clinical findings included intractable jaw pain mimicking that of
      odontogenic origin but unresponsive to usual therapies, minimal or undetectable
      radiographic abnormalities on plain films but dramatic radiolucencies detected on
      cone beam computed tomography, and large cavities that were either empty or
      filled with blood mixed with lipid globules encountered at surgery. The most
      common histomorphologic findings were vital lamellar bone, prominent resting and
      reversal lines, microshards and splaying of trabeculae, rounded trabeculae,
      marrow fibrosis, and pools of erythrocytes and lipid globules, often together.
      Moderate to complete relief of symptoms for periods up to 108 months after
      surgery were reported by 83% of the 70 patients who returned the survey.
      CONCLUSIONS: On the basis of the findings of this study, CFOJ can be considered a
      unique entity with consistent clinicopathologic features. Its features suggest a
      pathogenesis based on bone marrow ischemia. CFOJ can be treated on a rational
      basis with a justifiable expectation of success and probable cure.

PMID- 28754379
TI  - beta2-adrenoceptor-induced modulation of transglutaminase 2 transamidase activity
      in cardiomyoblasts.
AB  - Tissue transglutaminase 2 (TG2) is modulated by protein kinase A (PKA) mediated
      phosphorylation: however, the precise mechanism(s) of its modulation by G-protein
      coupled receptors coupled to PKA activation are not fully understood. In the
      current study we investigated the potential regulation of TG2 activity by the
      beta2-adrenoceptor in rat H9c2 cardiomyoblasts. Transglutaminase transamidation
      activity was assessed using amine-incorporating and protein cross-linking assays.
      TG2 phosphorylation was determined via immunoprecipitation and Western blotting.
      The long acting beta2-adrenoceptor agonist formoterol induced time- and
      concentration-dependent increases in TG2 transamidation. Increases in TG2
      activity were reduced by the TG2 inhibitors Z-DON (Benzyloxycarbonyl-(6-Diazo-5
      oxonorleucinyl)-L-valinyl-L-prolinyl-L-leucinmethylester) and R283 ((1,3,dimethyl
      2[2-oxo-propyl]thio)imidazole chloride). Responses to formoterol were blocked by
      pharmacological inhibition of PKA, extracellular signal-regulated kinase 1 and 2
      (ERK1/2), or phosphatidylinositol 3-kinase (PI-3K) signalling. Furthermore, the
      removal of extracellular Ca2+ also attenuated formoterol-induced TG2 activation.
      Fluorescence microscopy demonstrated TG2-induced biotin-X-cadaverine
      incorporation into proteins. Formoterol increased the levels of TG2-associated
      phosphoserine and phosphothreonine, which were blocked by inhibition of PKA,
      ERK1/2 or PI-3K signalling. Subsequent proteomic analysis identified known (e.g.
      lactate dehydrogenase A chain) and novel (e.g. Protein S100-A6) protein
      substrates for TG2. Taken together, the data obtained suggest that beta2
      adrenoceptor-induced modulation of TG2 represents a novel paradigm in beta2
      adrenoceptor cell signalling, expanding the repertoire of cellular functions
      responsive to catecholamine stimulation.

PMID- 28754380
TI  - Magnetocapillary self-assemblies: Locomotion and micromanipulation along a liquid
      interface.
AB  - This paper presents an overview and discussion of magnetocapillary self
      assemblies. New results are presented, in particular concerning the possible
      development of future applications. These self-organizing structures possess the
      notable ability to move along an interface when powered by an oscillatory,
      uniform magnetic field. The system is constructed as follows. Soft magnetic
      particles are placed on a liquid interface, and submitted to a magnetic induction
      field. An attractive force due to the curvature of the interface around the
      particles competes with an interaction between magnetic dipoles. Ordered
      structures can spontaneously emerge from these conditions. Furthermore, time
      dependent magnetic fields can produce a wide range of dynamic behaviours,
      including non-time-reversible deformation sequences that produce translational
      motion at low Reynolds number. In other words, due to a spontaneous breaking of
      time-reversal symmetry, the assembly can turn into a surface microswimmer.
      Trajectories have been shown to be precisely controllable. As a consequence, this
      system offers a way to produce microrobots able to perform different tasks. This
      is illustrated in this paper by the capture, transport and release of a floating
      cargo, and the controlled mixing of fluids at low Reynolds number.

PMID- 28754381
TI  - Toward the development of biomimetic injectable and macroporous biohydrogels for
      regenerative medicine.
AB  - Repairing or replacing damaged human tissues has been the ambitious goal of
      regenerative medicine for over 25years. One promising approach is the use of
      hydrated three-dimensional scaffolds, known as hydrogels, which have had good
      results repairing tissues in pre-clinical trials. Benefiting from breakthrough
      advances in the field of biology, and more particularly regarding cell/matrix
      interactions, these hydrogels are now designed to recapitulate some of the
      fundamental cues of native environments to drive the local tissue regeneration.
      We highlight the key parameters that are required for the development of smart
      and biomimetic hydrogels. We also review the wide variety of polymers,
      crosslinking methods, and manufacturing processes that have been developed over
      the years. Of particular interest is the emergence of supramolecular chemistries,
      allowing for the development of highly functional and reversible biohydrogels.
      Moreover, advances in computer assisted design and three-dimensional printing
      have revolutionized the production of macroporous hydrogels and allowed for more
      complex designs than ever before with the opportunity to develop fully
      reconstituted organs. Today, the field of biohydrogels for regenerative medicine
      is a prolific area of research with applications for most bodily tissues. On top
      of these applications, injectable hydrogels and macroporous hydrogels (foams)
      were found to be the most successful. While commonly associated with cells or
      biologics as drug delivery systems to increase therapeutic outcomes, they are
      steadily being used in the emerging fields of organs-on-chip and hydrogel
      assisted cell therapy. To highlight these advances, we review some of the recent
      developments that have been achieved for the regeneration of tissues, focusing on
      the articular cartilage, bone, cardiac, and neural tissues. These biohydrogels
      are associated with improved cartilage and bone defects regeneration, reduced
      left ventricular dilation upon myocardial infarction and display promising
      results repairing neural lesions. Combining the benefits from each of these areas
      reviewed above, we envision that an injectable biohydrogel foam loaded with
      either stem cells or their secretome is the most promising hydrogel solution to
      trigger tissue regeneration. A paradigm shift is occurring where the combined
      efforts of fundamental and applied sciences head toward the development of
      hydrogels restoring tissue functions, serving as drug screening platforms or
      recreating complex organs.

PMID- 28754382
TI  - Recent advances in studying single bacteria and biofilm mechanics.
AB  - Bacterial biofilms correspond to surface-associated bacterial communities
      embedded in hydrogel-like matrix, in which high cell density, reduced diffusion
      and physico-chemical heterogeneity play a protective role and induce novel
      behaviors. In this review, we present recent advances on the understanding of how
      bacterial mechanical properties, from single cell to high-cell density community,
      determine biofilm tri-dimensional growth and eventual dispersion and we attempt
      to draw a parallel between these properties and the mechanical properties of
      other well-studied hydrogels and living systems.

PMID- 28754383
TI  - Structures of apolipoprotein A-I in high density lipoprotein generated by
      electron microscopy and biased simulations.
AB  - BACKGROUND: Apolipoprotein A-I (apoA-I) in high-density lipoprotein (HDL) is a
      key protein for the transport of cholesterol from the vascular wall to the liver.
      The formation and structure of nascent HDL, composed of apoA-I and phospholipids,
      is critical to this process. METHODS: The HDL was assembled in vitro from apoA-I,
      cholesterol and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at a
      1:4:50 molar ratio. The structure of HDL was investigated in vitreous samples,
      frozen at cryogenic temperatures, as well as in negatively stained samples by
      transmission electron microscopy. Low resolution electron density maps were next
      used as restraints in biased Monte Carlo simulations of apolipoprotein A-I
      dimers, with an initial structure derived from atomic resolution X-ray
      structures. RESULTS: Two final apoA-I structure models for the full-length
      structure of apoA-I dimer in the lipid bound conformation were generated, showing
      a nearly circular, flat particle with an uneven particle thickness. CONCLUSIONS:
      The generated structures provide evidence for the discoidal, antiparallel
      arrangement of apoA-I in nascent HDL, and propose two preferred conformations of
      the flexible N-termini. GENERAL SIGNIFICANCE: The novel full-length structures of
      apoA-I dimers deepens the understanding to the structure-function relationship of
      nascent HDL with significance for the prevention of lipoprotein-related disease.
      The biased simulation method used in this study provides a powerful and
      convenient modelling tool with applicability for structural studies and modelling
      of other proteins and protein complexes.

PMID- 28754384
TI  - Expression and characterization of the ferritin binding domain of Nuclear
      Receptor Coactivator-4 (NCOA4).
AB  - Ferritinophagy is the process of autophagic degradation of ferritin that
      participates in the regulation of cellular iron homeostasis. This process was
      shown to be mediated by the selective cargo-receptor Nuclear Receptor Coactivator
      4 (NCOA4) that binds ferritin and targets it to emerging autophagosome. To
      characterize some of the biochemical properties of the interaction between the
      two proteins we cloned and expressed in E. coli the ferritin-binding domain of
      human NCOA4, fragment 383-522. It was purified and subjected to biochemical
      analysis. The NCOA4(383-522) fragment was expressed in soluble and dimeric form,
      and CD spectra indicated low level of secondary structure. The Ferritin binding
      activity of the fragment was investigated by developing an electrophoretic
      mobility shift and an ELISA assays. They showed that the NCOA4 fragment binds the
      H-ferritin with an affinity in the nM range, but not the R23A H-ferritin mutant
      and the L-ferritin chain, confirming the high specificity for the H-chain. The H
      ferritin could bind up to 24 NCOA4(383-522) fragments forming highly stable and
      insoluble complexes. The binding was partially inhibited only by Fe(II) among the
      various divalent metal ions analyzed. The iron-dependent, highly-specific
      formation of the remarkably stable H-ferritin-NCOA4 complex shown in this work
      may be important for the characterization of the mechanism of ferritinophagy.

PMID- 28754385
TI  - Alignment of actin filament streams driven by myosin motors in crowded
      environments.
AB  - BACKGROUND: Cellular dynamics depend on cytoskeletal filaments and motor
      proteins. Collective movements of filaments driven by motor proteins are observed
      in the presence of dense filaments in in vitro systems. As multiple
      macromolecules exist within cells and the physiological ionic conditions affect
      their interactions, crowding might contribute to ordered cytoskeletal
      architecture because of collective behavior. METHODS: Using an in vitro
      reconstituted system, we observed the emergence of stripe patterns resulting from
      collective actin filament streaming driven by myosin motors in the presence of
      the crowding agent, methylcellulose (MC). RESULTS: Although at high KCl
      concentrations (150mM), actin filaments tended to dissociate from a myosin-coated
      surface, 1% MC prevented this dissociation and enabled filament movement on
      myosin molecules. At concentrations of actin filaments above 0.2mg/mL, the moving
      filaments accumulated and progressively formed long, dense bands. The bands were
      spaced at about 10-MUm intervals. Increasing the KCl concentration up to 300mM
      resulted in narrowing of the spacing between the aligned bands. On the other
      hand, low KCl concentrations (<=25mM) induced broad streams, where actin
      filaments exhibited bidirectional movement. CONCLUSIONS: These results suggest
      that crowded environments can promote spatial patterning of the actin
      cytoskeleton, depending on the intensity of the myosin driving force and filament
      velocity, both modulated by the ionic strength. GENERAL SIGNIFICANCE: The mutual
      contribution of packing and driving forces provides insight into cytoskeleton
      organization in living cells, in which various macromolecules mingle.

PMID- 28754386
TI  - Sex-Specific Differences in the Association Between Childhood Adversity and
      Cardiovascular Disease in Adulthood: Evidence From a National Cohort Study.
AB  - BACKGROUND: Childhood adversity increases the risk for cardiovascular disease
      (CVD) in adulthood. Previously proposed mechanisms suggest that the association
      is mediated by stress reactivity-known to be higher in women-and is aggravated by
      adult stress, but this has not yet been confirmed. Therefore, we investigated sex
      differences to better understand possible pathways from childhood adversity to
      CVD. METHODS: The National Population Health Survey, a 15-year cohort study of
      Canadians aged 18-49 years at baseline was used. Logistic regression with
      interaction terms for sex and stressful life events was used to assess the risk
      of CVD after childhood adversity. In secondary analyses, we assessed mediation
      effects of depression, smoking, alcohol, exercise, and diet using the product of
      coefficient approach. Mediated moderation was subsequently used to explain sex
      moderated effects. RESULTS: There was a strong association between childhood
      adversity and CVD (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.56
      2.94) for 3+ childhood adversities. The association was stronger with increasing
      stressful events, and female patients with 3+ stressful events exhibited the
      highest risk of CVD (OR, 4.40; 95% CI, 1.98-9.75). No association was found in
      men. Depression, smoking, and poor diet partially mediated the relationship
      between childhood adversity and CVD (14%, 9%, and 9%, respectively), but
      differences in these behaviours did not fully explain the sex-specific
      differences in the mediated moderation analysis. CONCLUSIONS: The effect of
      childhood adverse events on CVD is heightened among women, particularly women
      with stressful adulthoods, and this difference is not mediated by depression,
      smoking, or poor diet. These findings have important implications for
      understanding sex differences in CVD risk.

PMID- 28754387
TI  - Cost of Cardiac Surgery in Frail Compared With Nonfrail Older Adults.
AB  - BACKGROUND: Frailty is a risk factor for mortality, morbidity, and prolonged
      length of stay after cardiac surgery, all of which are major drivers of
      hospitalization costs. The incremental hospitalization costs incurred in frail
      patients have yet to be elucidated. METHODS: Patients aged >= 60 years were
      evaluated for frailty before coronary artery bypass grafting or heart valve
      surgery at 2 academic centres between 2013 and 2015 as part of the McGill Frailty
      Registry. Total costs were summed from the date of the index surgery to the date
      of hospital discharge. Mutivariable linear regression was used to determine the
      association between preoperative frailty status and total costs after adjusting
      for conventional surgical risk factors. RESULTS: Among 235 patients included in
      the analysis, the median age was 73.0 years (interquartile range [IQR], 70.0-78.0
      years) and 68 (29%) were women. The median cost was $32,742 (IQR, $23,221
      $49,627) in 91 frail patients compared with $23,370 (IQR, $19,977-$29,705) in 144
      nonfrail patients. Seven extreme-cost cases > $100,000 were identified, and all
      of the patients in these cases exhibited baseline frailty. In the multivariable
      model, total costs were independently associated with frailty (adjusted
      additional cost, $21,245; 95% confidence interval [CI], $12,418-$30,073; P <
      0.001) and valve surgery (adjusted additional cost, $20,600; 95% CI, $9,661
      $31,539; P < 0.001). CONCLUSIONS: Frailty is associated with a marked increase in
      hospitalization costs after cardiac surgery, an effect that persists after
      adjusting for age, sex, surgery type, and surgical risk score. Further efforts
      are needed to optimize care and resource use in this vulnerable population.

PMID- 28754388
TI  - Rationale, Design and Baseline Characteristics of Participants in the
      Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS)
      Trial.
AB  - BACKGROUND: Long-term aspirin prevents vascular events but is only modestly
      effective. Rivaroxaban alone or in combination with aspirin might be more
      effective than aspirin alone for vascular prevention in patients with stable
      coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as
      well as aspirin increase upper gastrointestinal (GI) bleeding and this might be
      prevented by proton pump inhibitor therapy. METHODS: Cardiovascular Outcomes for
      People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority
      trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once
      daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention
      of myocardial infarction, stroke, or cardiovascular death in patients with stable
      CAD or PAD. Patients not taking a proton pump inhibitor were also randomized,
      using a partial factorial design, to pantoprazole 40 mg once daily or placebo.
      The trial was designed to have at least 90% power to detect a 20% reduction in
      each of the rivaroxaban treatment arms compared with aspirin and to detect a 50%
      reduction in upper GI complications with pantoprazole compared with placebo.
      RESULTS: Between February 2013 and May 2016, we recruited 27,395 participants
      from 602 centres in 33 countries; 17,598 participants were included in the
      pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years,
      22.0% were female, 90.6% had CAD, and 27.3% had PAD. CONCLUSIONS: COMPASS will
      provide information on the efficacy and safety of rivaroxaban, alone or in
      combination with aspirin, in the long-term management of patients with stable CAD
      or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI
      complications in patients receiving antithrombotic therapy.

PMID- 28754389
TI  - Interpatient Variation in Rivaroxaban and Apixaban Plasma Concentrations in
      Routine Care.
AB  - BACKGROUND: Direct-acting oral anticoagulants (DOACs) are widely prescribed for
      stroke prevention in patients with atrial fibrillation (AF). An important
      advantage of DOACs is that routine monitoring of an anticoagulation response is
      not necessary. Nevertheless, because of their mechanism of action, a DOAC
      anticoagulation effect can be inferred based on the observed plasma
      concentration. However, there is a paucity of data relating to observed
      interpatient variation in DOAC plasma concentrations in the postmarket clinical
      setting. METHODS: We determined rivaroxaban and apixaban plasma concentrations in
      patients with AF during routine clinic visits. RESULTS: Among 243 patients
      (rivaroxaban, n = 94; apixaban, n = 149) enrolled in this study, a 60- and 50
      fold interpatient variation in plasma concentration was observed for rivaroxaban
      and apixaban, respectively. Approximately 12% of patients receiving rivaroxaban
      and 13% of patients receiving apixaban exceeded the 95th percentile for predicted
      maximum plasma concentration observed in clinical trials. CONCLUSIONS: In this
      routine-care setting, rivaroxaban and apixaban plasma concentrations tended to be
      more variable than those observed in clinical trials. Identification of
      additional clinical and molecular determinants that more fully predict patients
      at risk for excessively high or low DOAC concentrations may enable a more precise
      DOAC dosing regimen for the individual patient.

PMID- 28754390
TI  - Bariatric Surgery-Induced Lower Angiopoietin-Like 2 Protein Is Associated With
      Improved Cardiometabolic Profile.
AB  - BACKGROUND: Plasma angiopoietin-like 2 (Angptl2), a proinflammatory protein, has
      been associated with obesity and diabetes. Whether weight loss induced by
      bariatric surgery and associated improvement of the cardiometabolic risk profile
      influence circulating Angptl2 levels is unknown. We tested whether
      biliopancreatic diversion with duodenal switch (BPD-DS) surgery alters plasma
      Angptl2 concentrations. METHODS: Severely obese patients (n = 73; body mass
      index: 49.8 +/- 7.1) underwent BPD-DS. Plasma levels of Angptl2 and metabolic
      biomarkers were obtained acutely (days 1 and 5) and at 6 and 12 months after
      surgery, and compared with results in an age- and sex-matched control group (n =
      33) remaining on the waiting list. RESULTS: Preoperative Angptl2 levels were high
      (median: 12.3 ng/mL) and correlated with metabolic and anthropometric parameters.
      A significant (P < 0.01) increase in Angptl2 levels, fasting glucose, insulin,
      and interleukin-6 levels was observed acutely postoperatively (day 1) followed by
      a progressive decline from day 5. Besides weight loss, Angptl2 levels were
      decreased at the 12-month follow-up (11.5 +/- 4.7 vs 14.0 +/- 4.0 ng/mL, P <
      0.0001), but not at the 6-month time point. Long-term changes in plasma Angptl2
      levels showed significant positive correlations with changes in fasting glucose,
      insulin resistance, and tumour necrosis factor-alpha levels, and negative
      correlation with changes in leptin concentration (P < 0.05). No significant
      correlation was observed between changes in anthropometric parameters and
      Angptl2. CONCLUSIONS: Plasma Angptl2 levels decreased after BPD-DS in severely
      obese patients; no changes occurred in control participants. Lowered circulating
      levels of the inflammatory factor Angptl2 because of BPD-DS were closely related
      to favourable changes in glucose-insulin homeostasis and inflammatory profiles.

PMID- 28754391
TI  - Validity of Health Administrative Database Definitions for Hypertension: A
      Systematic Review.
AB  - BACKGROUND: Health administrative data are frequently used for hypertension
      surveillance. The aim of this systematic review was to determine the sensitivity
      and specificity of the commonly used hypertension case definition of 2 physician
      outpatient claims within a 2-year period or 1 hospital discharge abstract record.
      METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines, we searched MEDLINE (from 1946) and EMBASE (from
      1947) for relevant studies through September 2016 (keywords: "hypertension,"
      "administrative databases," "validation studies"). Data with standardized forms
      and assessed quality using Quality Assessment of Diagnostic Accuracy Studies
      criteria were reviewed by 2 reviewers. Pooled sensitivity and specificity were
      estimated using a generalized linear-model approach to random-effects bivariate
      regression meta-analysis. RESULTS: The search strategy identified 1732 abstracts,
      among which 3 articles were deemed relevant. One of the articles incorporated 2
      studies with differing reference standards and study populations; thus, we
      considered each separately. The quality scores of the retained studies ranged
      from 10-12 of a maximum 14. The sensitivity of the definition investigated to
      identify hypertension using administrative health databases was 71.2% (95%
      confidence interval [CI], 68.3-73.7) and the specificity was 94.5% (95% CI, 93.2
      95.6) when compared with surveys or medical records. CONCLUSIONS: The 2 physician
      outpatient claims within a 2-year period or 1 hospital discharge abstract record
      hypertension case definition accurately classifies individuals as hypertensive in
      approximately 70% of cases and correctly identifies persons as nonhypertensive in
      approximately 95% of cases. This is likely sufficiently sensitive and specific
      for most research and surveillance purposes.

PMID- 28754392
TI  - Bridged Bilateral Superior Venae Cavae With Direct Left Atrial Appendage
      Connection and No Other Congenital Cardiac Anomaly.
AB  - A persistent left superior vena cava (SVC) results from failed obliteration of
      the left common cardinal vein during embryogenesis, with a spectrum of anatomic
      variants. We report a rare case of bilateral SVCs connected by a bridging vein
      and with a direct left SVC connection to the left atrial appendage in an
      asymptomatic patient without hypoxemia or associated congenital heart disease on
      transthoracic echocardiography, computed tomography, and magnetic resonance
      imaging. A multimodality imaging approach is valuable to search for associated
      anomalies and to confirm this anatomic variant, which has important implications
      on vascular procedures and avoidance of systemic embolism.

PMID- 28754393
TI  - Totally Leadless Dual-Device Implantation for Combined Spontaneous Ventricular
      Tachycardia Defibrillation and Pacemaker Function: A First Report.
AB  - Subcutaneous implantable cardioverter defibrillators (S-ICDs) provide effective
      defibrillation, while also reducing the risk of long-term lead problems. However,
      S-ICDs do not offer bradycardia or antitachycardia pacing and therefore use has
      been limited. Combined implantation of an S-ICD with a leadless pacemaker (LP)
      has been proposed to overcome this limitation. Although a handful of combined S
      ICD/LP implantations have been reported for Nanostim (St Jude Medical, St Paul,
      MN) as well as Micra LP (Medtronic, Minneapolis, MN) systems, none have
      documented delivery of appropriate shock therapies for spontaneous ventricular
      tachycardia. We report the first case of effective defibrillation for spontaneous
      ventricular tachycardia in a patient with combined Micra LP and S-ICD.

PMID- 28754394
TI  - A Potentially Lethal Dysfunction of a Subcutaneous Implantable Cardiac
      Defibrillator: "The Phantom Menace"?
AB  - In this article we describe, to our knowledge, the first case of a potentially
      lethal dysfunction of a subcutaneous implantable cardioverter-defibrillator (S
      ICD). A 70-year-old patient underwent primary S-ICD implantation. Nine months
      after, communication could not be established with the device. Chest radiography
      revealed that the lead had moved and wrapped around the generator. After
      equipment extraction, we observed the lead wound around the sagittal axis of the
      generator. A burn mark with melted metal was found inside the generator. Our
      hypothesis is an electric arc occurred between the retracted lead and the
      generator. This could be the first reported Reel syndrome secondary to S-ICD
      implantation.

PMID- 28754395
TI  - Canadian Physician Attitudes and Practices Regarding Periprocedural Management of
      Oral Anticoagulation for Cardiac Catheterization.

PMID- 28754396
TI  - Measuring Blood Pressure and Diagnosing Hypertension in the Physicians Office in
      the Age of Automated Devices: Time for Guidelines to Reflect Reality.

PMID- 28754397
TI  - Contemporary Atrial Fibrillation Management: A Comparison of the Current
      AHA/ACC/HRS, CCS, and ESC Guidelines.
AB  - In this article we compare and contrast the current recommendations, and
      highlight the important differences, in the American College of
      Cardiology/American Heart Association/Heart Rhythm Society, European Society of
      Cardiology, and Canadian Cardiovascular Society atrial fibrillation (AF)
      guidelines. Although many of the recommendations of the various societies are
      similar, there are important differences in the methodologies underlying their
      development and the specific content. Specifically, key differences can be
      observed in: (1) the definition of nonvalvular AF, which subsequently affects
      anticoagulation choices and candidacy for non-vitamin K antagonist oral
      anticoagulants; (2) the symptom score used to guide management decisions and
      longitudinal patient profiling; (3) the stroke risk stratification algorithm used
      to determine indications for oral anticoagulant therapy; (4) the role of
      acetylsalicylic acid in stroke prevention in AF; (5) the antithrombotic regimens
      used in the context of coronary artery disease, acute coronary syndromes, and
      percutaneous coronary intervention; (6) the rate control target and medications
      recommended to achieve the target; and (7) the role of "first-line" catheter
      ablation, open surgical ablation, and left atrial appendage exclusion.

PMID- 28754398
TI  - Management of Implantable Cardioverter Defibrillator Recipients: Care Beyond
      Guidelines.
AB  - This companion article is intended to address common clinical scenarios in
      patients with implantable defibrillators that were not addressed in the 2016
      Canadian Cardiovascular Society/Canadian Heart Rhythm Society implantable
      cardioverter defibrillator guidelines including recommendations for device
      programming to improve detection, to minimize shocks (appropriate and
      inappropriate), and to minimize ventricular pacing. Important issues at the time
      of replacement such as device prescription, technical aspects (vascular access,
      extraction), and management of components on advisories are also discussed.
      Finally, common clinical scenarios such as management of patients with terminal
      illnesses, recurrent ventricular tachycardia, electrical storms, catheter
      ablation for ventricular tachycardia, and system infection management are
      considered. The management of these patients requires a team approach and
      comprehensive knowledge surrounding these common clinical scenarios.

PMID- 28754399
TI  - Relation Between Superficial Calcifications and Plaque Rupture: An Optical
      Coherence Tomography Study.
AB  - BACKGROUND: There are several forms of calcium deposition, which play different
      roles in the stability of the coronary artery. It remains unknown whether certain
      calcification morphological characteristics determine rupture of lipid-rich
      lesions in the same plaque in acute coronary syndrome (ACS). METHODS: We
      retrospectively analyzed 550 patients with ACS between May 2008 and October 2014,
      who had undergone preintervention optical coherence tomography (OCT) imaging
      examination. A total of 78 patients with 78 culprit lipid-rich lesions having
      superficial calcifications on OCT images were included in this study, among which
      45 were ruptured lesions with calcium and 33 were nonruptured lipid-rich lesion
      with calcium. The smallest depth of calcium (CAL-DEP) was determined, and the
      morphology of the calcifications and plaques was analyzed during preintervention
      OCT imaging. RESULTS: The CAL-DEP was significantly thinner in ruptured lesions
      with calcium than in nonruptured lipid-rich lesion with calcium (median, 50
      [interquartile range (IQR), 33-63] MUm vs 110 [73-208] MUm; P < 0.001) and in
      myocardial infarction than in unstable angina pectoris patients (median, 57 [IQR,
      36-78] MUm vs median, 85 [IQR, 43-140] MUm; P = 0.045). For lipid-rich calcified
      plaques, when CAL-DEP was < 63 MUm, the lipid-rich lesion was most vulnerable and
      prone to rupture (sensitivity = 77.8%; specificity = 81.8%; area under the curve:
      0.804; P < 0.0001). CONCLUSIONS: Small CAL-DEP in lipid-rich calcified plaques is
      a morphological characteristic of a vulnerable plaque phenotype. A CAL-DEP <= 63
      MUm is the critical depth of calcification for lipid-rich calcified plaque
      rupture in patients with ACS.

PMID- 28754400
TI  - Isolated limb perfusion with cytostatic drug leakage.
AB  - Isolated limb perfusion is the treatment of stage III melanoma with in-transit
      metastasis. This technique allows the administration of cytostatics at an
      effective concentration and temperature, which could not be administered
      systemically because of their toxicity. The toxicity due to leakage of the
      chemotherapy agent from the limb into the systemic circulation is the most
      serious short-term complication, and is manifested by a systemic inflammatory
      response syndrome in the immediate post-intervention period. Early detection of
      this complication and its peri-operative management requires a multidisciplinary
      approach, in which the anaesthesiologist plays a key role. A case of isolated
      lower limb perfusion is reported in which the procedure had to be interrupted due
      to the passage of tumour necrosis factor into the systemic circulation, with
      severe intra-operative haemodynamic repercussions.

PMID- 28754401
TI  - [Introduction: The renewal of face- and neck-lift?]

PMID- 28754402
TI  - Cardiovascular risk factors in patients with spondyloarthritis from Northern
      European and Mediterranean countries: An ancillary study of the ASAS-COMOSPA
      project.
AB  - OBJECTIVES: The objectives of this study were: (1) to compare the prevalence of
      cardiovascular disease and cardiovascular risk factors among different phenotypes
      of spondyloarthritis (SpA); (2) to assess the differences in cardiovascular
      disease and cardiovascular risk factors between two geographical areas, i.e.
      Northern Europe vs. Mediterranean region; (3) to identify potential predictive
      factors for high Framingham Risk Score regarding disease features in SpA and
      geographical area. METHODS: Ancillary analysis of the international,
      multicentric, observational, cross-sectional ASAS-COMOSPA study. Cardiovascular
      disease and cardiovascular risk factors were compared depending on SpA phenotype
      and geographical regions. Potential factors associated with higher cardiovascular
      risk (i.e. Framingham Risk Score) were determined by a multiple logistic
      regression. RESULTS: The most frequent cardiovascular risk factor and
      cardiovascular disease were smoking (31.2%) and ischemic heart disease (3.2%),
      respectively. Regarding SpA phenotype, axial SpA patients showed significantly
      lower prevalence (P<0.05) of hypertension (19.2% vs. 33.8% vs. 26.6% for axial,
      peripheral and mixed phenotypes, respectively), type 2 diabetes mellitus (4.3%
      vs. 8.5% vs. 7.4%), dyslipidemia (13.9% vs. 28.4% vs. 15.2%) and ischemic heart
      disease (2.4% vs. 7.0% vs. 3.2%). Regarding geographical area, a higher frequency
      of hypertension (34.7% vs. 19.4%,), dyslipidemia (19.3% vs. 14.4%), obesity
      (29.3% vs. 20.7%) and ischemic heart disease (6.2% vs. 1.8%) was observed for
      Northern Europe vs. Mediterranean Region, respectively. CONCLUSIONS: Our results
      suggest that SpA phenotype and geographical area are associated with the
      prevalence of cardiovascular risk factors and the cardiovascular risk itself,
      observed in patients in the ASAS-COMOSPA cohort.

PMID- 28754403
TI  - [Clinical and pathological features of gastrointestinal stromal tumors (GIST) in
      a single institution: A descriptive study and review of the literature].
AB  - INTRODUCTION: This study was aimed to assess the main clinical, pathological and
      therapeutic characteristics of a cohort of gastrointestinal stromal tumors
      (GIST). METHODS: Observational study including 66 patients diagnosed with GIST
      admitted to our hospital between 2002 and 2015. Parameters related to medical
      history, clinical manifestations, medical and surgical treatment, histopathology,
      and morbi-mortality were studied. A review of the literature was included to
      correlate with the results. RESULTS: The most frequent location of GIST in our
      patients was the stomach (65.2%), in which the gastric fondo was the predominant
      region. The most common clinical manifestation was gastrointestinal hemorrhage
      (45.5%), followed by incidental finding after imaging or invasive procedures
      (33.3%). 58 patients underwent surgery (90.6%), 15.5% were urgent. A total of 69%
      of the GISTs had a size between 2 and 10cm. The one-year mortality was 7.9%, all
      cases related to local or remote extension, or surgical complications.
      CONCLUSION: There is a large clinical variability among GIST cases. The first
      choice of treatment is surgery, which is feasible in most cases and should be as
      conservative as possible. The prognosis varies depending on the size and
      proliferation index, thus close follow-up should be performed. No tumor marker is
      clearly associated with a poor prognosis. New molecular biology studies are
      needed in order to find therapeutic targets.

PMID- 28754404
TI  - Relevance of plasma levels of free homocysteine and methionine as risk predictors
      for ischemic stroke in the young.
AB  - BACKGROUND & AIMS: The debated vascular risk potential of total homocysteine
      (tHcy), due to failed clinical trials designed on B vitamin supplementation,
      raises many possible explanations like the higher risk potential of the
      deleterious, free form of homocysteine (fHcy) or, the unchecked confounding
      effects of B-vitamins in tHcy-based association studies. Additionally, the
      cardiovascular risk probability of altered status of the homocysteine precursor,
      methionine (tMet) could shed light on the causality of association between tHcy
      and cardiovascular diseases. Hence, we aimed to evaluate the risk associations of
      elevated plasma levels of tHcy, fHcy and low levels of tMet with premature,
      ischemic stroke. METHODS: We recruited 171 young, ischemic stroke patients (aged
      <=45 years) and 249 age- and gender-matched healthy controls. Plasma levels of
      fHcy, tHcy, tMet and vitamin B6 were estimated using HPLC coupled with
      coulometric electrochemical detection. Plasma levels of vitamin B12 and folate
      were estimated by radioimmunoassay. RESULTS: Elevated fHcy (>2.9 MUmol/L) was
      independently and strongly associated with the risk of premature, ischemic stroke
      (OR = 9.62, 95% CI = 3.51-26.40). On the contrary, association between premature
      ischemic stroke and elevated tHcy (>15.0 MUmol/L) was found to attenuate when
      adjusted for vitamin B6 values (OR = 0.24, 95%, CI = 0.03-1.69). Interestingly,
      compromised B6-status (<59.2 nmol/l) was found to confer high risk of premature
      ischemic stroke (OR = 170.80, 95% CI = 58.22-501.06). We could not establish any
      significant correlation between fHcy and B-vitamin levels (P > 0.05). Low tMet
      (<13.86 MUmol/L) was also not significantly associated with premature, ischemic
      stroke (OR = 2.53, 95% CI = 0.613-10.38). CONCLUSION: Our results indicate
      significant but not-correlated, independent associations of fHcy and vitamin B6
      with risk of premature, ischemic stroke. However, the causality of these
      associations need prospective and large scale validations. Further, our findings
      highlight the crucial confounding effects of B-vitamins on risk association
      between tHcy and premature ischemic stroke.

PMID- 28754405
TI  - Comprehensive cancer-related gene analysis reveals that active KRAS mutation is a
      prognostic mutation in mycosis fungoides.

PMID- 28754406
TI  - Antibiotic Use in 2016 by Members of the American Association of Endodontists:
      Report of a National Survey.
AB  - INTRODUCTION: This study surveyed the antibiotic prescribing practices of
      endodontists, and data were compared with previous surveys conducted in 1994 and
      1999. METHODS: A 17-question survey was sent via www.surveymonkey.com to 3000
      active members of the American Association of Endodontists for responses about
      antibiotic prescribing practices and demographics. The data were analyzed using
      descriptive statistics, chi-square tests, and linear regression analyses.
      RESULTS: Six hundred eighty-six participants (22.86%) completed the survey. The
      most frequently prescribed antibiotics were amoxicillin (60.71%) followed by
      penicillin V (30.43%) and clindamycin for patients with allergies (95.4%).
      Respondents reported prescribing antibiotics for irreversible pulpitis with mild
      symptoms (1.75%), irreversible pulpitis with moderate symptoms (6.41%), necrotic
      pulp with symptomatic apical periodontitis (43.59%), chronic apical abscess
      without (10.50%) or with symptoms (29.74%), acute apical abscess (95.92%),
      avulsion (70.26%), endodontic surgery (41.69%), retreatment (silver point
      [23.76%] or gutta-percha [15.60%]), postoperative pain after instrumentation or
      obturation (12.39%), and perforation repair (5.98%). The type of practice
      (solo/group) and geographic region (Southeast) were significant predictors of
      increased antibiotic prescribing; 36.89% of respondents reported prescribing
      antibiotics that are not necessary, most commonly because of patient
      expectations. CONCLUSIONS: Since 1999, there has been a significant shift from
      prescribing penicillin V to amoxicillin as endodontists' first choice of
      antibiotic and a significant increase in the use of clindamycin for penicillin
      allergic patients. Antibiotics continue to be prescribed in clinical situations
      for which they are typically not indicated, most commonly because of patient
      expectations. Regional differences in antibiotic prescribing practices by
      endodontists exist in the United States.

PMID- 28754407
TI  - Punishment of alcohol-reinforced responding in alcohol preferring P rats reveals
      a bimodal population: Implications for models of compulsive drug seeking.
AB  - Individual variations in animal behaviour can be used to describe relationships
      between different constructs, as well as the underlying neurobiological
      mechanisms responsible for such variation. In humans, variation in the expression
      of certain traits contributes to the onset of psychopathologies, such as drug
      addiction. Addiction is characterised by persistent drug use despite negative
      consequences, but it occurs in only a sub-population of drug users. Compulsive
      drug use is modelled in laboratory animals by punishing a drug-reinforced operant
      response. It has been reported that there is individual variability in the
      response to punishment, and in this report we aim to further define the
      conditions under which this variation can be observed. We have previously used
      footshock punishment to suppress alcohol seeking in an animal model of context
      induced relapse to alcohol seeking after punishment-imposed abstinence. Here we
      present a re-examination of the training and punishment data from a large cohort
      of rats (n=499) collected over several years. We found evidence for a bimodal
      distribution in the response to punishment in alcohol preferring P rats. We only
      observed this population split when rats received constant shock intensity for
      three sessions, but not when increasing shock intensity was used. This
      observation provides evidence for the existence of two distinct groups of rats,
      defined by their response to punishment, in an otherwise homogeneous population.
      The implications of this observation are discussed in reference to prior
      observations using punishment of other addictive drugs (cocaine and
      methamphetamine), the potential causes of this phenomenon, and with broader
      implications for the cause of alcohol and drug addiction in humans.

PMID- 28754408
TI  - Antipsychotics for aggression in adults: A meta-analysis.
AB  - Aggressive behavior complicates the presentation of many psychiatric illnesses,
      and is associated with significant morbidity. Antipsychotic medications are used
      to treat this symptom dimension across multiple diagnoses. In this meta-analysis
      we sought to identify the effect size of antipsychotic medications for the
      treatment of reactive-impulsive aggression in adults, and identify differences
      across underlying diagnosis and specific agent. A search was conducted of four
      databases, MEDLINE, PsychINFO, Embase and the Cochrane Library to end date of
      August 10, 2016. The search terms included "aggression", "irritable mood",
      "anger", "hostility" and "antipsychotic agents" or "dopamine antagonists". 505
      results were found, of which 47 were reviewed in detail and 21 ultimately
      included in the analysis. Antipsychotics were broadly effective for the treatment
      of aggression, but with effect sizes similar to those for non-pharmacologic
      interventions (standard mean difference=0.29, 95% confidence interval 0.22-0.36,
      z=8.5, p<0.001). There was no evidence for differences according to choice of
      agent (chi2=2.7, df=6, p=0.85), or conclusive evidence as to the importance of
      the underlying diagnosis (chi2=3.2, df=3, p=0.36). A small but significant dose
      effect was identified (beta=0.0002, 95% CI 0.0001-0.0004, p=0.038). Although
      antipsychotics appear to be effective for treatment of aggression, their small
      effect sizes in the context of their significant side-effects should be taken
      into account when making clinical decisions about their use.

PMID- 28754409
TI  - Rigorous analysis of static light scattering measurements on buffered protein
      solutions.
AB  - Attention is drawn to the thermodynamic invalidity of the current practice of
      analyzing static light scattering measurements on globular proteins in terms of
      theory for a single solute because of its disregard of the need to consider small
      species such as buffer components as additional cosolutes rather than as part of
      the solvent. This practice continues despite its demonstrated inadequacy in
      studies of sucrose-supplemented protein solutions, where the aberrant behavior
      was recognized to be a consequence of physical protein interaction with the small
      cosolute. Failure to take into account the consequences of small cosolute effects
      renders extremely difficult any attempt to obtain a rigorous thermodynamic
      characterization of protein interactions by this empirical technique.

PMID- 28754410
TI  - Laparoscopic Adjustable Gastric Band Explantation and Implantation at Academic
      Centers.
AB  - BACKGROUND: The laparoscopic adjustable gastric band (LAGB) was approved for use
      in the US in 2001 and has been found to be a safe and effective surgical
      treatment for morbid obesity. However, there is a recent trend toward reduced use
      of LAGB nationwide. The objective of this study was to examine the prevalence and
      outcomes of primary LAGB implantation compared with revision and explantation at
      academic centers. STUDY DESIGN: Data were obtained from the Vizient database from
      2007 through 2015. The ICD-9-Clinical Modification and ICD-10-Clinical
      Modification were used to select patients with a primary diagnosis of obesity who
      had undergone LAGB implantation, revision, or explantation. Prevalence and
      outcomes of primary LAGB implantation compared with revision or explantation were
      analyzed. Outcomes measures included length of stay, ICU admission, morbidity,
      mortality, and cost. RESULTS: From 2007 through 2015, a total of 28,202 patients
      underwent LAGB implantation for surgical weight loss. The annual number of LAGB
      implantation procedures decreased steadily after 2010. In the same time period,
      12,157 patients underwent LAGB explantation. In 2013, the number of LAGB
      explantation procedures exceeded that of implantation. Laparoscopic adjustable
      gastric band revision rates remained stable throughout the study period. Mean
      length of stay, serious morbidity, and proportion of patients requiring ICU
      admission were higher for gastric band revision and explantation cases compared
      with primary LAGB implantation cases. There was no statistically significant
      difference in mortality or mean cost between the 2 groups. CONCLUSIONS: Since
      2013, the number of gastric band explantation procedures has exceeded that of
      implantation procedures at academic centers. Laparoscopic adjustable gastric band
      revision or explantation is associated with longer length of stay, higher rate of
      postoperative ICU admissions, and higher overall morbidity compared with LAGB
      implantation.

PMID- 28754411
TI  - Acceleration tracking control combining adaptive control and off-line
      compensators for six-degree-of-freedom electro-hydraulic shaking tables.
AB  - An electro-hydraulic shaking table (EHST) is an essential experimental facility
      to simulate in real-time actual vibration situations. An adaptive controller
      combined with off-line compensators is proposed to improve the acceleration
      frequency bandwidth and tracking accuracy of a six-degree-of-freedom (6-DOF)
      EHST. A servo controller has been employed to implement acceleration closed-loop
      and coordinate control of the 6-DOF EHST. A recursive extended least-squares
      algorithm is employed to identify acceleration closed-loop transfer functions and
      a zero-phase-error tracking controller is used to design off-line inverse model
      compensators using the identified transfer functions. However, the off-line
      compensators cannot compensate in real-time varying dynamics of the 6-DOF EHST;
      so an online adaptive controller with a least-mean-squares (LMS) algorithm based
      on a delay compensator is employed. The proposed controller combines advantages
      of the off-line compensators and the online adaptive controller, which guarantees
      both a fast rate of convergence of the LMS algorithm and high-fidelity
      acceleration tracking accuracy of the 6-DOF EHST. Some experimental studies have
      been conducted on a 6-DOF EHST and experimental results show that acceleration
      tracking control performances, including the rate of convergence of the LMS
      algorithm and acceleration tracking accuracy, have been improved compared to a
      conventional three-variable controller and adaptive controllers.

PMID- 28754412
TI  - Design of multiloop PI controllers based on quadratic optimal approach.
AB  - The LQR methodology is extended to produce multiloop PI controllers in this
      study. With this method, a multivariable P controller is first obtained and then
      diagonalized using an iterative procedure. The resulting controller is further
      complemented with the integral action in a similar process. The proposed tuning
      process explores different values of the control weight matrix to balance the
      output error and control signal in both stages, and is refined through additional
      indices related with the error to reference tracking, disturbance rejection and
      the associated control use. In addition, the diagonalization procedure is
      generalized to obtain multiloop versions of existing multivariable PI
      controllers. The developed theory was applied to the design of multiloop
      controllers for a distillation column as well as the diagonalization of existing
      controllers for a nonlinear CSTR. The tuning procedure allowed the synthesis of
      multiloop PI controllers with performance indices comparable to those reported by
      other authors. Furthermore, diagonalized controllers exhibited a similar
      operation as the original multivariable ones.

PMID- 28754413
TI  - Direct energy balance based active disturbance rejection control for coal-fired
      power plant.
AB  - The conventional direct energy balance (DEB) based PI control can fulfill the
      fundamental tracking requirements of the coal-fired power plant. However, it is
      challenging to deal with the cases when the coal quality variation is present. To
      this end, this paper introduces the active disturbance rejection control (ADRC)
      to the DEB structure, where the coal quality variation is deemed as a kind of
      unknown disturbance that can be estimated and mitigated promptly. Firstly, the
      nonlinearity of a recent power plant model is analyzed based on the gap metric,
      which provides guidance on how to set the pressure set-point in line with the
      power demand. Secondly, the approximate decoupling effect of the DEB structure is
      analyzed based on the relative gain analysis in frequency domain. Finally, the
      synthesis of the DEB based ADRC control system is carried out based on multi
      objective optimization. The optimized ADRC results show that the integrated
      absolute error (IAE) indices of the tracking performances in both loops can be
      simultaneously improved, in comparison with the DEB based PI control and
      Hinfinity control system. The regulation performance in the presence of the coal
      quality variation is significantly improved under the ADRC control scheme.
      Moreover, the robustness of the proposed strategy is shown comparable with the
      Hinfinity control.

PMID- 28754414
TI  - Control-oriented modeling and adaptive backstepping control for a nonminimum
      phase hypersonic vehicle.
AB  - In this paper, the nonminimum phase problem of a flexible hypersonic vehicle is
      investigated. The main challenge of nonminimum phase is the prevention of dynamic
      inversion methods to nonlinear control design. To solve this problem, we make
      research on the relationship between nonminimum phase and backstepping control,
      finding that a stable nonlinear controller can be obtained by changing the
      control loop on the basis of backstepping control. By extending the control loop
      to cover the internal dynamics in it, the internal states are directly controlled
      by the inputs and simultaneously serve as virtual control for the external
      states, making it possible to guarantee output tracking as well as internal
      stability. Then, based on the extended control loop, a simplified control
      oriented model is developed to enable the applicability of adaptive backstepping
      method. It simplifies the design process and releases some limitations caused by
      direct use of the no simplified control-oriented model. Next, under proper
      assumptions, asymptotic stability is proved for constant commands, while bounded
      stability is proved for varying commands. The proposed method is compared with
      approximate backstepping control and dynamic surface control and is shown to have
      superior tracking accuracy as well as robustness from the simulation results.
      This paper may also provide a beneficial guidance for control design of other
      complex systems.

PMID- 28754415
TI  - Prospects and Challenges towards Sustainable Liver Fluke Control.
AB  - The liver fluke Opisthorchis viverrini (Ov) is endemic in Southeast Asia where
      more than 10 million people are estimated to be infected. The infection is
      associated with several hepatobiliary diseases, including cholangiocarcinoma
      (CCA). Northeast Thailand is a hotspot for Ov transmission, and, despite
      extensive public health prevention campaigns led by the government, the
      prevalence of Ov infection is still high. High infection rates result from
      cultural and ecological complexities where wet-rice agrarian habitats, centuries
      old raw-food culture, and the parasite's complex biology combine to create an
      ideal transmission arena. Here we review the state of our knowledge regarding the
      social-ecological determinants underlying Ov transmission. We also describe an
      integrative research rationale for liver fluke control better aligned with
      sustainable health development.

PMID- 28754416
TI  - Paramphistomosis of Ruminants: An Emerging Parasitic Disease in Europe.
AB  - Whilst historically regarded as being of minor importance in European livestock,
      recent evidence suggests that the prevalence of paramphistomosis is greater than
      that of fasciolosis in parts of the UK. In order to address this emerging threat
      to ruminant farming systems, and associated risks for food security posed by
      rumen fluke infection, it is imperative that we develop a better understanding of
      the basic biology of this parasite and how it interacts with its ruminant host.
      In this Opinion article we review recent progress in tracking the spread of rumen
      fluke infection in Europe, and propose some research questions that should be
      addressed if we are to develop tools to diagnose and treat paramphistomosis more
      effectively in the future.

PMID- 28754417
TI  - Marked response to pembrolizumab in a patient with pulmonary pleomorphic
      carcinoma highly positive for PD-L1.

PMID- 28754418
TI  - Surgical treatment of adrenal carcinoma.
AB  - Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. The
      presence of a mass syndrome or signs of hormonal hypersecretion often lead to its
      discovery, but more and more frequently, adrenocortical malignancy is
      fortuitously discovered as an incidentaloma. Cross-sectional imaging (CT and MRI)
      often points to the malignant character of the adrenal mass. Needle biopsy is
      contraindicated. Laboratory testing showing combined hypersecretion of cortisol,
      androgens or inactive corticosteroid precursors is highly suggestive of ACC. An
      18F-fluoro-deoxyglucose Positron Emission Tomography (PET scan) should be
      performed to evaluate the malignancy of an adrenal mass and to detect regional or
      distant metastases. Although the majority of ACC are diagnosed at a locally
      advanced or metastatic stage, radical resection offers the only hope of cure. The
      peri-operative management of patients with ACC is not yet standardized. The aim
      of this review is to summarize the actual knowledge of the surgical management of
      ACC.

PMID- 28754419
TI  - Evaluation of tolerance to lentiviral LV-RPE65 gene therapy vector after
      subretinal delivery in non-human primates.
AB  - Several approaches have been developed for gene therapy in RPE65-related Leber
      congenital amaurosis. To date, strategies that have reached the clinical stages
      rely on adeno-associated viral vectors and two of them documented limited long
      term effect. We have developed a lentiviral-based strategy of RPE65 gene transfer
      that efficiently restored protein expression and cone function in RPE65-deficient
      mice. In this study, we evaluated the ocular and systemic tolerances of this
      lentiviral-based therapy (LV-RPE65) on healthy nonhuman primates (NHPs), without
      adjuvant systemic anti-inflammatory prophylaxis. For the first time, we describe
      the early kinetics of retinal detachment at 2, 4, and 7 days after subretinal
      injection using multimodal imaging in 5 NHPs. We revealed prolonged reattachment
      times in LV-RPE65-injected eyes compared to vehicle-injected eyes. Low- (n = 2)
      and high-dose (n = 2) LV-RPE65-injected eyes presented a reduction of the outer
      nuclear and photoreceptor outer segment layer thickness in the macula, that was
      more pronounced than in vehicle-injected eyes (n = 4). All LV-RPE65-injected eyes
      showed an initial perivascular reaction that resolved spontaneously within 14
      days. Despite foveal structural changes, full-field electroretinography indicated
      that the overall retinal function was preserved over time and
      immunohistochemistry identified no difference in glial, microglial, or leucocyte
      ocular activation between low-dose, high-dose, and vehicle-injected eyes.
      Moreover, LV-RPE65-injected animals did not show signs of vector shedding or
      extraocular targeting, confirming the safe ocular restriction of the vector. Our
      results evidence a limited ocular tolerance to LV-RPE65 after subretinal
      injection without adjuvant anti-inflammatory prophylaxis, with complications
      linked to this route of administration necessitating to block this transient
      inflammatory event.

PMID- 28754420
TI  - Identifying changes in gait waveforms following a strengthening intervention for
      women with knee osteoarthritis using principal components analysis.
AB  - Lower limb strengthening exercise is pivotal for the management of symptoms
      related to knee osteoarthritis (OA). Though improvement in clinical symptoms is
      well documented, concurrent changes in gait biomechanics are ill-defined. This
      may occur because discrete analyses miss changes following an intervention,
      analyses limited to the knee undermine potential mechanical trade-offs at other
      joints, or strengthening interventions not been designed based on biomechanical
      principles. The purpose of this study was to characterize differences in entire
      gait waveforms for sagittal plane ankle, knee, and hip angles and external
      moments; the knee adduction moment; and frontal plane hip angle and moment
      following 12-weeks of a previously designed novel lower limb strengthening
      program. Forty women with knee OA completed two laboratory visits: one at
      baseline and one immediately following intervention (follow-up). Self-report
      measures, strength, and gait analyses were completed at each visit. Principal
      components analyses were completed for sagittal angles and external moments at
      the ankle, knee, and hip joints, as well as frontal plane angle and moment for
      the hip. Participants improved self-report and strength (p<=0.004). Two
      significant, yet subtle differences in principal components were identified
      between baseline and follow-up waveforms (p<0.05) pertaining to the knee and hip
      sagittal external moments. The subtle changes in concert with the lack of
      differences in other joints and planes suggest the lower limb strengthening
      program does not translate to changes in the gait waveform. It is likely this
      program is improving symptoms without worsening mechanics.

PMID- 28754421
TI  - The effect of visual focus on spatio-temporal and kinematic parameters of
      treadmill running.
AB  - The characteristics of a treadmill and the environment where it is based could
      influence the user's gaze and have an effect on their running kinematics and
      lower limb impacts. The aim of this study was to identify the effect of visual
      focus on spatio-temporal parameters and lower limb kinematics during treadmill
      running. Twenty six experienced runners ran at 3.33ms-1 on a treadmill under two
      visual conditions, either looking ahead at a wall or looking down at the
      treadmill visual display. Spatio-temporal parameters, impact accelerations of the
      head and tibia, and knee and ankle kinematics were measured for the final 15s of
      a 90s bout of running under each condition. At the end of the test, participants
      reported their preference for the visual conditions assessed. Participants'
      stride angle, flight time, knee flexion during the flight phase, and ankle
      eversion during contact time were increased when runners directed visual focus
      toward the wall compared to the treadmill display (p<0.05). Whilst head
      acceleration was also increased in the wall condition (p<0.05), the other
      acceleration parameters were unaffected (p>0.05). However, the effect size of all
      biomechanical alterations was small. The Treadmill condition was the preferred
      condition by the participants (p<0.001; ESw=1.0). The results of the current
      study indicate that runners had a greater mass centre vertical displacement when
      they ran looking ahead, probably with the aim of compensating for reduced visual
      feedback, which resulted in larger head accelerations. Greater knee flexion
      during the flight phase and ankle eversion during the contact time were suggested
      as compensatory mechanisms for lower limb impacts.

PMID- 28754422
TI  - State of the art: Vest Nile Virus circulation surveillance in Italy and
      transfusion risk early prevention methods.
AB  - After the Chikungunya outbreak in 2007 in Italy, a national Plan for the
      surveillance of human vector-borne diseases has been implemented and annually
      updated on the basis of the epidemiological changes based-evidences. The
      transfusion Authorities cooperates, since 2008, with public health services and
      veterinary (entomological and ornithological) surveillance systems. In some
      Italian regions, a common protocol for exchanging data is in place to identify
      the West Nile Virus (WNV) circulation in birds and mosquitoes: the goal is to
      anticipate the introduction of WNV-NAT screening in blood donors and, on the
      other hand, to limit testing only in geographic areas where the virus circulation
      is actual. The integration of surveillance activities and a multidisciplinary
      approach made it possible to introduce efficient and preventive measures for
      reducing the risk of of transmission of WNV trough blood, tissues and organ
      donation.

PMID- 28754423
TI  - Gender differences and outcomes in left ventricular assist device support: The
      European Registry for Patients with Mechanical Circulatory Support.
AB  - BACKGROUND: Despite the increasing use of ventricular assist devices (VADs),
      gender differences in indications, hemodynamics, and outcome are not well
      understood. We examined gender differences and gender-specific predictors for
      perioperative outcome in patients on ventricular support. METHODS: Multicenter
      data of 966 patients (median age 55 years, 151 women) from the European Registry
      for Patients with Mechanical Circulatory Support (EUROMACS) were analyzed. Median
      follow-up was 1.26 years. RESULTS: At the time of VAD implantation, women were
      more often in an unstable condition (Interagency Registry for Mechanically
      Assisted Circulatory Support [INTERMACS] profile 1 and 2) (51.7% vs 41.6% in
      men), experiencing significantly more often major bleeding (p = 0.0012),
      arrhythmias (p = 0.022), and right ventricular (RV) failure (p < 0.001) with need
      for additional RV support. The survival of women on isolated LVAD support was
      significantly worse (1-year survival 75.5% vs 83.2% in men). Age-adjusted Cox
      regression analyses showed significant associations with mortality for
      preoperative inotropic therapy, percutaneous mechanical support, INTERMACS
      profile 1 and 2, RV dysfunction, major bleeding, cerebral bleeding, ischemic
      stroke, and RV failure. In women, pump thrombosis was more strongly related with
      mortality compared to men, while the direction of the association of renal
      dysfunction with mortality was different for women and men (p-value interaction
      0.028 and 0.023, respectively). CONCLUSIONS: Women and men differ in
      perioperative hemodynamics, adverse events, and mortality after VAD implantation.
      A gender-dependent association of pump thrombosis with mortality was seen. The
      impact on treatment practice needs to be shown.

PMID- 28754424
TI  - Pharmacist perceptions of competency: Identifying priority areas for a competency
      program development at an academic medical center.
AB  - BACKGROUND: Competency-based education models can serve as valuable resources for
      providing quality continuing education and professional development in
      healthcare. However, competency development programs can be stifled by scarce
      stakeholder involvement and insufficient recognition of resource challenges.
      Engaging pharmacists in program development can inform program design and
      prioritization of needs. OBJECTIVE: To describe a process to assess pharmacist
      perceptions about competency development and to inform program design by
      identifying high priority topic areas based on perceived value, confidence in
      abilities, and frequency of use by pharmacists. METHODS: Pharmacists at a large
      academic medical center were surveyed to examine opinions regarding competency
      development and identify perceived departmental value, personal confidence, and
      frequency of use for nine competency topic areas. Responses were aggregated to
      create scores for each of the three criteria related to the nine topics. Priority
      areas were topics with the highest relative scores in perceived value and
      frequency of use and lowest relative scores in confidence compared to the other
      areas. RESULTS: Survey responses were collected from 105 pharmacists (78.9%
      response rate). A majority indicated that competency assessment is a shared
      responsibility between the organization and individual pharmacists. Therapeutic
      knowledge was identified as the competency requiring the most immediate attention
      as it was perceived to have the highest departmental value and highest frequency
      of use, yet participants indicated low confidence regarding the topic.
      CONCLUSIONS: Competency development is a critical aspect of ensuring pharmacists
      are prepared for the rapidly evolving needs of the healthcare system.
      Organizations play an important role in identifying and developing pharmacist
      competencies aligned with institutional and individual needs. This study suggests
      that pharmacists and leaders at an academic medical center identified a shared
      responsibility for competency development. The process described here may provide
      a model for other medical centers with similar competency development needs.

PMID- 28754425
TI  - Thoroughness of community pharmacists' assessment and communication using the
      patient care process.
AB  - BACKGROUND: The patient care process (PCP) was adopted to move community pharmacy
      practice from the traditional dispensing role to a more professional level of
      patient care. However, research has not yet empirically characterized how
      pharmacists conduct the PCP in community pharmacies. OBJECTIVES: This study
      characterizes how pharmacists employ the PCP when evaluating medication
      appropriateness in a simulated community pharmacy setting. METHODS: A mixed
      methods analysis was employed to analyze simulated patient-pharmacist
      interactions (i.e., consultations), and concurrent think-aloud (checking
      sessions). Transcripts were quantitatively coded for elements of the PCP. A
      generic qualitative approach was used to explore how pharmacists provided care.
      RESULTS: Almost all pharmacists checked for medication indication, safety, and
      manageability at the end of the process when releasing the medication to the
      patient. Still, most pharmacists gathered insufficient information to fully
      evaluate medication appropriateness. Six overarching themes described
      consultations and checking sessions: missed opportunities, the absence of
      personalized assessments, reliance on routines, nonspecific questions,
      communication style, and response to patient cues. The quantitative and
      qualitative findings together created a picture of incomplete assessments which
      were driven by technical routines and medication-focused communication.
      CONCLUSION: Overall, the majority of pharmacists completed most of the patient
      care process. Even so, pharmacists did not complete a full assessment of
      medication appropriateness. Patient care tasks were driven by routines and
      occurred at the end of the process, whereas the initial patient assessment and
      prescription check were mainly devoted to technical activities. Pharmacists had
      opportunities to enhance patient-centered communication by engaging patients in
      dialogue and recognizing patient emotional cue.

PMID- 28754426
TI  - Relevance of multidrug-resistant Pseudomonas aeruginosa infections in cystic
      fibrosis.
AB  - Multidrug-resistant (MDR) Pseudomonas aeruginosa is an important issue for
      physicians who take care of patients with cystic fibrosis (CF). Here, we review
      the latest research on how P. aeruginosa infection causes lung function to
      decline and how several factors contribute to the emergence of antibiotic
      resistance in P. aeruginosa strains and influence the course of the infection
      course. However, many aspects of the practical management of patients with CF
      infected with MDR P. aeruginosa are still to be established. Less is known about
      the exact role of susceptibility testing in clinical strategies for dealing with
      resistant infections, and there is an urgent need to find a tool to assist in
      choosing the best therapeutic strategy for MDR P. aeruginosa infection. One
      current perception is that the selection of antibiotic therapy according to
      antibiogram results is an important component of the decision-making process, but
      other patient factors, such as previous infection history and antibiotic courses,
      also need to be evaluated. On the basis of the known issues and the best current
      data on respiratory infections caused by MDR P. aeruginosa, this review provides
      practical suggestions to optimize the diagnostic and therapeutic management of
      patients with CF who are infected with these pathogens.

PMID- 28754427
TI  - Abnormally High Ankle-Brachial Index is Associated with All-cause and
      Cardiovascular Mortality: The REGICOR Study.
AB  - INTRODUCTION: The clinical significance of a high ankle brachial index (ABI) and
      its relationship to cardiovascular disease (CVD) and mortality is controversial.
      The aim of this study was to estimate the association between abnormally high ABI
      >= 1.4 and coronary heart disease (CHD), cerebrovascular disease, and all-cause
      mortality in a Mediterranean population without CVD. METHODS: A prospective
      population based cohort study of 6352 subjects was followed up for a median 6.2
      years. Subjects under 35 years, with a history of CVD or an ABI < 0.9 were
      excluded. All CHD events (angina, myocardial infarction, coronary
      revascularisation), cerebrovascular events (stroke, transient ischaemic attack),
      and all-cause mortality were recorded. RESULTS: A total of 5679 subjects
      fulfilled the inclusion criteria, of which 5517 (97.1%) had a normal ABI whereas
      162 (2.9%) had an ABI >= 1.4. The profile of individuals with abnormally high ABI
      revealed as independent related factors age (OR = 1.0; p = .045), female sex (OR
      = 0.4; p < .01), diabetes (OR = 1.9; p = .02), and lower diastolic blood pressure
      (OR = 0.9; p < .001). During follow-up 309 (5.4%) participants presented with a
      CV event and 286 (5.0%) died. An ABI >= 1.4 was associated with a higher
      incidence of CV events in the univariate (HR = 1.7) but not in the multivariate
      survival Cox regression analysis. An ABI >= 1.4 was independently associated with
      all-cause mortality (HR = 2.0; IC 95% 1.32-2.92) and cardiovascular mortality (HR
      = 3.1; IC 95% 1.52-6.48). CONCLUSIONS: In subjects without CVD, those with
      abnormally high ABI do not have a greater CV event rate than those with a normal
      ABI. However, there seems to be a trend towards higher mortality risk, supporting
      the guidelines that consider this subgroup to be a high risk population.

PMID- 28754428
TI  - Mid-term Results of Chimney and Periscope Grafts in Supra-aortic Branches in High
      Risk Patients.
AB  - PURPOSE: Report mid-term outcomes of thoracic endovascular aneurysm repair
      (TEVAR) with chimney and periscope grafts (CPG) in supra-aortic branches (SAB).
      METHODS: Retrospective analysis, from October 2009 to May 2014, of patients with
      aneurysms requiring TEVAR with zone 0/1/2 proximal landing in association with at
      least one CPG in the SAB. All patients were considered at high risk for
      conventional surgery. Peri-operative mortality and morbidity, retrograde type A
      dissection, maximum aortic transverse diameter (TD) and its post-operative
      evolution, endoleak, survival, freedom from cardiovascular re-interventions, and
      CPG freedom from occlusion during the follow-up were analysed. RESULTS: Forty-one
      patients (28.05% EuroScore II) with thoraco-abdominal aortic aneurysm (17%), arch
      aneurysm (39%), descending aneurysm (34%), and aneurysm extending from the arch
      to the visceral aorta (10%) were included. Fifteen (37%) patients were treated
      non-electively. Fifty-nine SABs were treated with the CPG technique: one, two,
      three, and four CPG were employed in 71%, 19%, 5%, and 5% of patients,
      respectively. The proximal landing was in zone 0 in 49% of patients, zone 1 in
      17%, and zone 2 in 34%. Technical success was 95%. Peri-operative complications
      and neurological events were registered in six (14.6%) patients and there were 5
      deaths (12%). At a median follow-up of 21.2 (mean 22, SD 18; range 0-65) months,
      type I/III endoleaks were registered in three (7%) cases and re-intervention in
      six (15%) patients. A significant aneurysm sac shrinkage (p<.001) was reported at
      mean follow-up and no significant aneurysm sac increase (>5 mm). The estimated 2
      year survival, freedom from re-intervention, freedom from endoleak, and freedom
      from branch occlusion were 75%, 77%, 86%, and 96%, respectively. CONCLUSION: The
      chimney and periscope grafts technique was shown to be safe in aortic aneurysm
      disease involving the supra aortic branches, even in an emergency setting using
      off the shelf devices. Mid-term follow-up results in this high risk population
      are good, but longer follow-up is mandatory before this technique is used in
      intermediate-risk patients.

PMID- 28754429
TI  - Assessment of Minimum Important Difference and Substantial Clinical Benefit with
      the Vascular Quality of Life Questionnaire-6 when Evaluating Revascularisation
      Procedures in Peripheral Arterial Disease.
AB  - OBJECTIVES: Patient reported outcomes are increasingly used to assess outcomes
      after peripheral arterial disease (PAD) interventions. VascuQoL-6 (VQ-6) is a PAD
      specific health-related quality of life (HRQoL) instrument for routine clinical
      practice and clinical research. This study assessed the minimum important
      difference for the VQ-6 and determined thresholds for the minimum important
      difference and substantial clinical benefit following PAD revascularisation.
      MATERIALS AND METHODS: This was a population-based observational cohort study. VQ
      6 data from the Swedvasc Registry (January 2014 to September 2016) was analysed
      for revascularised PAD patients. The minimum important difference was determined
      using a combination of a distribution based and an anchor-based method, while
      receiver operating characteristic curve analysis (ROC) was used to determine
      optimal thresholds for a substantial clinical benefit following
      revascularisation. RESULTS: A total of 3194 revascularised PAD patients with
      complete VQ-6 baseline recordings (intermittent claudication (IC) n = 1622 and
      critical limb ischaemia (CLI) n = 1572) were studied, of which 2996 had complete
      VQ-6 recordings 30 days and 1092 a year after the vascular intervention. The
      minimum important difference 1 year after revascularisation for IC patients
      ranged from 1.7 to 2.2 scale steps, depending on the method of analysis. Among
      CLI patients, the minimum important difference after 1 year was 1.9 scale steps.
      ROC analyses demonstrated that the VQ-6 discriminative properties for a
      substantial clinical benefit was excellent for IC patients (area under curve
      (AUC) 0.87, sensitivity 0.81, specificity 0.76) and acceptable in CLI (AUC 0.736,
      sensitivity 0.63, specificity 0.72). An optimal VQ-6 threshold for a substantial
      clinical benefit was determined at 3.5 scale steps among IC patients and 4.5 in
      CLI patients. CONCLUSIONS: The suggested thresholds for minimum important
      difference and substantial clinical benefit could be used when evaluating VQ-6
      outcomes following different interventions in PAD and in the design of clinical
      trials.

PMID- 28754430
TI  - Glycemic control and health-related quality of life among older home-dwelling
      primary care patients with diabetes.
AB  - AIMS: To evaluate the health-related quality of life (HRQoL) and functional
      capacity in relation to glycemic control among older home-dwelling primary care
      patients. METHODS: Electronic patient records were used to identify 527 people
      over 65 years with diabetes. Of these, 259 randomly selected subjects were
      invited to a health examination and 172 of them attended and provided complete
      data. The participants were divided into three groups based on the HbA1c: good
      (HbA1c<48mmol/mol (N=95)), intermediate (HbA1c 48-57mmol/mol (N=48)) and poor
      (HbA1c>57mmol/mol (N=29)) glycemic control. HRQoL was measured with the EuroQol
      EQ-5D questionnaire. Functional and cognitive capacity and mental well-being were
      assessed with the Lawton Instrumental Activities of Daily Living (IADL) scale,
      Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS-15).
      RESULTS: EQ-5D scores for good, intermediate and poor glycemic control were 0.78;
      0.74 and 0.70, p=0.037. Sub-items of mobility (p=0.002) and self-care were the
      most affected (p=0.031). Corresponding trend was found for IADL, p=0.008. A
      significant correlation was found between MMSE scores and HbA1c. CONCLUSION:
      Older primary care home-dwelling patients with diabetes and poorer glycemic
      control have lower functional capacity and HRQoL, especially in regard to
      mobility and self-care.

PMID- 28754431
TI  - Recommendations of the Brazilian Society of Rheumatology for the induction
      therapy of ANCA-associated vasculitis.
AB  - The purpose of these recommendations is to guide the appropriate induction
      treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV)
      patients with active disease. The recommendations proposed by the Vasculopathies
      Committee of the Brazilian Society Rheumatology for induction therapy of AAV,
      including granulomatosis with polyangiitis, microscopic polyangiitis and renal
      limited vasculitis, were based on systematic literature review and expert
      opinion. Literature review was performed using Medline (PubMed), EMBASE and
      Cochrane database to retrieve articles until October 2016. PRISMA guidelines were
      used for the systematic review and articles were assessed according to the Oxford
      levels of evidence. Sixteen recommendations were made regarding different aspects
      of induction therapy for AAV. The purpose of these recommendations is to serve as
      a guide for therapeutic decisions by health care professionals in the management
      of AAV patients presenting active disease.

PMID- 28754432
TI  - The 5 choice continuous performance test (5C-CPT): A novel tool to assess
      cognitive control across species.
AB  - BACKGROUND: Neurodevelopmental disorders including Tourette's syndrome (TS) and
      attention deficit hyperactivity disorder (ADHD) are characterized by significant
      impairment in attention and cognitive control. These cognitive deficits persist
      throughout development, contribute significantly to socio-occupational
      impairment, and are relatively impervious to available treatment. A critical
      challenge in pro-cognitive drug discovery is translatability of findings across
      species, underscoring the need for developing valid and reliable cross-species
      cognitive tasks. NEW METHOD: Here we describe a cross-species 5 choice continuous
      performance task that was developed to measure cognitive control processes of
      attention, vigilance, and response inhibition, enabling the translation of
      findings for pro-cognitive drug discovery across species and delineate neural
      mechanisms underlying cognitive control construct. RESULTS: Construct validity of
      5C-CPT has been verified by multiple cross-species studies. Several lines of
      evidence report consistent findings across species including, deficits resulting
      from 36-h sleep deprivation studies, engagement of parietal cortex in human brain
      imaging and rodent lesion studies, and vigilance decrements over time. COMPARISON
      WITH EXISTING METHOD: Unlike the widely used rodent 5 choice serial reaction time
      task (5CSRTT) and the sustained attention task (SAT), the rodent 5C-CPT includes
      both target and non-target stimuli that allow measuring of cognitive control
      elements including response inhibition, an ability to inhibit pre-potent response
      during non-target trials, detect vigilance decrement and calculate signal
      detection parameters in rodents analogous to human CPT. CONCLUSION: The cross
      species 5C-CPT is a robust translational tool to characterize the neurobiological
      substrates underlying cognitive control deficits in clinical population
      including, ADHD and TS and develop targeted pro-cognitive therapeutics.

PMID- 28754433
TI  - A novel, double intra-carotid cannulation technique to study the effect of
      central nutrient sensing on glucose metabolism in the rat.
AB  - BACKGROUND: The hypothalamus plays a key role in central nutrient sensing and
      glucose homeostasis. Due to its position next to the third ventricle,
      intracerebroventricular (ICV) injections or osmotic minipumps are widely applied
      techniques in studying effects of hormones and other molecules on the
      hypothalamus and glucose metabolism. NEW METHODS: The intracarotid catheter
      technique in which a catheter is placed in the carotid artery, pointing towards
      the brain, provides a physiological route to centrally infuse blood-borne
      molecules in an undisturbed animal. To measure effects of central interventions
      on peripheral glucose metabolism, endogenous glucose production (EGP) and insulin
      sensitivity can be measured using a stable isotope technique. To combine both
      techniques, it is necessary to combine different catheters. We here describe a
      novel cannulation technique for the carotid artery, enabling stress-free
      infusions towards the brain and blood sampling from the carotid artery
      concomitantly, and infuse a stable isotope via the jugular vein. RESULTS: We
      showed accurate EGP measurements when intracarotically infusing saline towards
      the brain. The stress-hormone corticosterone, as well as energy expenditure, did
      not alter upon central infusion. COMPARISON EXISTING METHOD(S): ICV infusions
      bypass the blood-brain-barrier (BBB) and are thus a less physiological approach
      when studying central effects of blood-borne factors. Furthermore, ICV injections
      can elicit a stress response which can interfere with outcomes of glucose
      metabolism. We described a stress-free, physiological method to study effects of
      central infusions on peripheral parameters. CONCLUSIONS: This technique provides
      new opportunities for studying central effects of, for instance, hormones and
      nutrients, on glucose metabolism.

PMID- 28754434
TI  - Improved method for cannula fixation for long-term intracerebral brain infusion.
AB  - BACKGROUND: Implanted osmotic minipumps are commonly used for long-term, brain
      targeted delivery of a wide range of experimental agents by being connected to a
      catheter and a cannula. During the stereotactical surgery procedure, the cannula
      has to be placed correctly in the x-y directions and also with respect to the
      injection point in the z-direction (deepness). However, the flat fixation base of
      available cannula holders doesn't allow an easy, secure fixation onto the curve
      shaped skull. NEW METHOD: We have developed a modified method for a better
      fixation of the cannula holder by using an easy-to-produce, skull-shaped silicone
      spacer as fixation adapter. RESULTS: We describe the application and its fast and
      reliable production in the lab. COMPARISON WITH EXISTING METHOD(S): Superglue or
      cement is currently being used as the method of choice. However, the curve-shaped
      skull surface does not fit well with the flat and rigid cannula adapter which
      leads to fixation problems over time causing wide infusion channels and often
      also to leakage problems from intracerebrally applied agents towards the surface
      meninges. As another consequence of the inappropriate fixation, the cannula may
      loosen from the skull before the end of the experiment or it causes damage to the
      brain tissue, harming the animals with leading to a failure of the whole
      experiment. CONCLUSIONS: The easy-to-produce spacer facilitates the crucial step
      of long-term, stereotactic brain infusion experiments with intracerebral
      catheters in a highly secure and reproducible way.

PMID- 28754435
TI  - Children With Type 1 Diabetes Have Delayed Flow-Mediated Dilation.
AB  - OBJECTIVES: Children with type 1 diabetes have accelerated atherosclerosis with
      early endothelial dysfunction as measured by reduced flow-mediated dilation (FMD)
      at 60 seconds postischemic stress (early FMD). Delayed dilation may also occur in
      the presence of cardiovascular risk factors and may be a more sensitive marker.
      No data exist that evaluate FMD beyond 60 seconds (delayed FMD) in children with
      type 1 diabetes. We aimed to compare early and delayed FMD in children with type
      1 diabetes and in healthy children. METHODS: We studied 66 children 13.5+/-2.8
      years of age; 29 were males. Of the 66 children, 38 had type 1 diabetes, and 28
      were healthy age- and gender-matched controls. Evaluation of brachial artery FMD
      was performed at 60 seconds (FMD60s) and 120 seconds (FMD120s) postischemic
      stress. Early FMD was defined as peak FMD60s and delayed FMD as peak FMD120s.
      RESULTS: Children with type 1 diabetes had diabetes durations of 5.4+/-4.6 years
      and median glycated hemoglobin levels of 8.8 (6.6 to 14)% (73 [49 to 130]
      mmol/mol). Of the children, 8 with type 1 diabetes and 1 healthy child had
      delayed FMD; a relationship was seen between the prevalence of early FMD and
      delayed FMD in children with type 1 diabetes and healthy children, respectively
      (p=0.019). Children with type 1 diabetes and delayed FMD had lower FMD60s than
      children without delayed FMD (2.50+/-3.61 vs. 6.14+/-3.83 percentage units;
      p=0.02). Children with type 1 diabetes had lower FMD60s than healthy children
      (5.38+/-4.0 percentage units; p=0.03) but not FMD120s (7.56+/-3.5 percentage
      units; p=0.47). CONCLUSIONS: Delayed FMD patterns occur in children with type 1
      diabetes and detect children who have more severe vascular abnormalities. The
      standard FMD60s remains the better marker to identify children at increased risk
      for cardiovascular disease.

PMID- 28754436
TI  - Sex differences in coronary atherosclerosis progression and major adverse cardiac
      events in patients with suspected coronary artery disease.
AB  - BACKGROUND: Little is known about the influence of coronary atherosclerosis
      progression on the risk of major adverse cardiac events (MACE). Similarly,
      differences between men and women regarding atherosclerosis progression are
      poorly understood. The purpose of this study was to investigate the progression
      of coronary atherosclerosis by coronary CT angiography (coronary CTA) in men and
      women, and to evaluate its prognostic value regarding MACE. METHODS: This study
      included 1046 patients with suspected coronary artery disease (CAD) who underwent
      serial coronary CTA because of new or worsening symptoms or because follow-up
      coronary CTA had been recommended by attending physicians. Coronary
      atherosclerosis was semi-quantitatively assessed as follows: three-vessel plaque
      score (TVPS), severe proximal plaque score (SPPS), segment stenosis score (SSS),
      segment involvement score (SIS), and coronary artery calcium score (CACS).
      Patients were followed-up regarding the occurrence of MACE, defined as cardiac
      death, coronary revascularization, nonfatal myocardial infarction and
      hospitalization due to unstable angina. Follow-up information was gathered by
      clinical visits or telephone contacts. RESULTS: Follow-up was achieved in 953
      (91.1%) patients (63.8% male; mean age, 53.9 +/- 9.7 years) with a mean interval
      of 4.9 +/- 1.1 years. MACE occurred in 132 (13.9%) patients. The average
      interscan time was 2.1 years. Compared with women, men had significantly higher
      progression of SPPS, SSS and SIS (6.6% vs. 3.5%, 28.0% vs. 18.3%, 26.6% vs.
      16.8%, respectively, all P < 0.005). There was a strong association between the
      progression of SPPS as well as SSS and MACE, both for men (SPPS, HR:2.17, P <
      0.001; SSS, HR:1.28, P = 0.023) and women (SPPS, HR:2.75, P < 0.001; SSS,
      HR:1.19, P = 0.027). CONCLUSIONS: Progression of coronary atherosclerosis as
      determined by coronary CTA is higher in men than women, it is associated with the
      risk of future MACE.

PMID- 28754437
TI  - Inactivation of the orphan nuclear receptor NR4A1 contributes to apoptosis
      induction by fangchinoline in pancreatic cancer cells.
AB  - Previous studies have demonstrated that the orphan nuclear receptor NR4A1 is
      overexpressed in human pancreatic cancer and antagonizing this receptor promotes
      apoptosis and inhibits pancreatic cancer cells and tumor growth. In the present
      study, we identified fangchinoline, a bisbenzyltetrahydroisoquinoline alkaloid
      from Stephania tetrandra, as a new inactivator of nuclear NR4A1 and demonstrated
      that fangchinoline inhibits cell proliferation and induces apoptosis, in part,
      via the NR4A1-dependent pro-apoptotic pathways in human pancreatic cancer cells.
      It decreased expression of the antiapoptotic protein survivin by inhibiting Sp1
      mediated transcription and induced oxidative stress-mediated endoplasmic
      reticulum (ER) stress in pancreatic cancer cells. These results suggest that
      inhibition of NR4A1-mediated transcriptional activity was involved in the
      anticancer effects of fangchinoline, and fangchinoline represents a novel class
      of mechanism-based anticancer agents targeting NR4A1 that is overexpressed in
      pancreatic cancer.

PMID- 28754438
TI  - Cost-effectiveness of treatments for heavy menstrual bleeding.
AB  - BACKGROUND: Heavy menstrual bleeding affects up to one third of women in the
      United States, resulting in a reduced quality of life and significant cost to the
      health care system. Multiple treatment options exist, offering different
      potential for symptom control at highly variable initial costs, but the relative
      value of these treatment options is unknown. OBJECTIVE: The objective of the
      study was to evaluate the relative cost-effectiveness of 4 treatment options for
      heavy menstrual bleeding: hysterectomy, resectoscopic endometrial ablation,
      nonresectoscopic endometrial ablation, and the levonorgestrel-releasing
      intrauterine system. STUDY DESIGN: We formulated a decision tree evaluating
      private payer costs and quality-adjusted life years over a 5 year time horizon
      for premenopausal women with heavy menstrual bleeding and no suspected
      malignancy. For each treatment option, we used probabilities derived from
      literature review to estimate frequencies of minor complications, major
      complications, and treatment failure resulting in the need for additional
      treatments. Treatments were compared in terms of total average costs, quality
      adjusted life years, and incremental cost-effectiveness ratios. Probabilistic
      sensitivity analysis was conducted to understand the range of possible outcomes
      if model inputs were varied. RESULTS: The levonorgestrel-releasing intrauterine
      system had superior quality-of-life outcomes to hysterectomy with lower costs. In
      a probabilistic sensitivity analysis, levonorgestrel-releasing intrauterine
      system was cost-effective compared with hysterectomy in the majority of scenarios
      (90%). Both resectoscopic and nonresectoscopic endometrial ablation were
      associated with reduced costs compared with hysterectomy but resulted in a lower
      average quality of life. According to standard willingness-to-pay thresholds,
      resectoscopic endometrial ablation was considered cost effective compared with
      hysterectomy in 44% of scenarios, and nonresectoscopic endometrial ablation was
      considered cost effective compared with hysterectomy in 53% of scenarios.
      CONCLUSION: Comparing all trade-offs associated with 4 possible treatments of
      heavy menstrual bleeding, the levonorgestrel-releasing intrauterine system was
      superior to both hysterectomy and endometrial ablation in terms of cost and
      quality of life. Hysterectomy is associated with a superior quality of life and
      fewer complications than either type of ablation but at a higher cost. For women
      who are unwilling or unable to choose the levonorgestrel-releasing intrauterine
      system as a first-course treatment for heavy menstrual bleeding, consideration of
      cost, procedure-specific complications, and patient preferences can guide the
      decision between hysterectomy and ablation.

PMID- 28754439
TI  - Myocardial blood flow reserve is impaired in patients with aortic valve
      calcification and unobstructed epicardial coronary arteries.
AB  - BACKGROUND: Although calcific aortic valve disease (CAVD) is associated with
      coronary atherosclerosis, it is not known whether early CAVD is associated with
      coronary microcirculatory dysfunction (CMD). We sought to investigate the
      relationship between myocardial blood flow reserve (MBFR) - a measure of CMD, and
      early CAVD in the absence of obstructive epicardial coronary artery disease. We
      also determined whether this relationship was independent of coronary artery
      disease (CAD) and hs-CRP, a marker of systemic inflammation. METHODS: 183
      patients with chest pain and unobstructed coronary arteries were studied. Aortic
      valve calcification score (AVCS), coronary total plaque length (TPL), and
      coronary calcium score were quantified from multislice CT. MBFR was assessed
      using vasodilator myocardial contrast echocardiography. Hs-CRP was measured from
      venous blood using a particle-enhanced immunoassay. RESULTS: Mean (+/-SD)
      participant age was 59.8 (9.6) years. Mean AVCS was 68 (258) AU, TPL was 15.6
      (22.2) mm, and median coronary calcification score was 43.5AU. Mean MBFR was 2.20
      (0.52). Mean hs-CRP was 2.52 (3.86) mg/l. Multivariable linear regression
      modelling incorporating demographics, coronary plaque characteristics, MBFR, and
      inflammatory markers, demonstrated that age (beta=0.05, 95% CI: 0.02, 0.08,
      P=0.007), hs-CRP (beta=0.09, CI: 0.02, 0.16, P=0.010) and diabetes (beta=1.03,
      CI: 0.08, 1.98, P=0.033), were positively associated with AVCS. MBFR (beta=-0.87,
      CI: -1.44, -0.30, P=0.003), BMI (beta=-0.11, CI: -0.21, -0.01, P=0.033), and LDL
      (beta=-0.32, CI: -0.61, -0.03, P=0.029) were negatively associated with AVCS. TPL
      and coronary calcium score were not independently associated with AVCS when
      included in the regression model. CONCLUSION: Coronary microvascular function as
      determined by measurement of myocardial blood flow reserve is independently
      associated with early CAVD. This effect is independent of the presence of
      coronary artery disease and also systemic inflammation.

PMID- 28754440
TI  - To Intubate or Not to Intubate: Emergency Medicine Physicians' Perspective on
      Intubating Critically Ill, Terminal Cancer Patients.
AB  - CONTEXT: Emergency physicians (EPs) often need to make a decision whether or not
      to intubate a terminal cancer patient. OBJECTIVE: The objective of this study was
      to explore EPs' attitudes about intubating critically ill, terminal cancer
      patients. METHODS: Fifty EPs at three emergency departments (one university
      based, one community, and one Health Maintenance Organization) in Southern
      California participated in an anonymous survey that presented a hypothetical case
      of an end-stage lung cancer patient in pending respiratory failure. Fourteen
      questions along a five-point Likert scale asked EPs about prognosis and factors
      that influence their decision to intubate or not. RESULTS: A convenience sampling
      of 50 EPs yielded a 100% survey response rate. Ninety-four percent believed
      intubation would not provide an overall survival benefit. If the family insisted,
      26% would intubate the patient even with a do-not-intubate (DNI) status. Ninety
      four percent would postpone intubation if palliative consultation were available
      in the ED. Sixty-eight percent believed that a discussion about goals of care was
      more time consuming than intubation. Only 16% believed they had sufficient
      training in palliative care. Although 29% who felt they had inadequate palliative
      care training would intubate the patient with a DNI, only 13% of EPs with self
      perceived adequate palliative care training would intubate that patient.
      CONCLUSION: EPs vary in their attitudes about intubating dying cancer patients
      when families demanded it, even when they believed it was nonbeneficial and
      against the patient's wishes. Palliative care education has the potential to
      influence that decision making. Intubation could be mitigated by the availability
      of palliative consultation in the ED.

PMID- 28754441
TI  - Supply-Side Differences Only Modestly Associated With Inpatient Hospitalizations
      Among Medicare Beneficiaries in the Last Six Months of Life.
AB  - CONTEXT: Inpatient hospitalizations are a driver of expenditures at the end of
      life and are a useful proxy for the intensity of care at that time. OBJECTIVES:
      Our study profiled rural and urban Medicare decedents to examine whether they
      differed in rates of inpatient hospital admissions in the last six months of
      life. METHODS: Using a sample of 35,831 beneficiaries from the 2013 Medicare
      Research Identifiable Files, we examined inpatient hospital utilization patterns
      for a full six months before death. Supply-side variables included the number of
      hospital beds, certified skilled nursing facility beds, and hospice beds per 1000
      residents, plus primary care provider/population ratios. Patient characteristics
      included age, sex, race/ethnicity, dual eligibility status, region, and chronic
      conditions. RESULTS: In both adjusted and unadjusted analysis, rural vs. urban
      residence was not associated with an increased risk for hospitalization at the
      end of life among Medicare beneficiaries nor was there a relationship between the
      supply of hospital, skilled nursing, and hospice services and the rate of
      hospitalization. Within rural residents alone, modest effects were found for
      facility supply. Rural residents in a county without a hospital were slightly
      less likely than other rural decedents to have been hospitalized during their
      last six months of life but were no less likely to have used skilled nursing
      facilities or hospice. CONCLUSIONS: The absence of major disparities in
      utilization suggests that end-of-life care is reasonably equitable for rural
      Medicare beneficiaries.

PMID- 28754442
TI  - Mechanotransduction at the cell-matrix interface.
AB  - The ability of cells to sense and respond to mechanical signals is vital in
      development and healthy tissue functioning. Many diseases are related to either
      changing mechanical properties of the tissue, or changes in the ability of cells
      to sense mechanical signals. This sensing occurs, in part, at integrin-associated
      complexes (IACs) that form sites of attachment between the cell and the
      extracellular matrix (ECM). In this review, we discuss the complex mechanical
      signals of the ECM. We will also outline how IACs are involved in cellular
      sensing of these mechanical properties, focussing on the molecular mechanisms of
      key adhesion molecules. Finally, the cellular mechanisms of mechanotransduction
      considering mechanosensing and signalling aspects of the core proteins in FAs are
      discussed and open questions outlined.

PMID- 28754443
TI  - Nanoscale mechanobiology of cell adhesions.
AB  - Proper physiological functions of cells and tissues depend upon their abilities
      to sense, transduce, integrate, and generate mechanical and biochemical signals.
      Although such mechanobiological phenomena are widely observed, the molecular
      mechanisms driving these outcomes are still not fully understood. Cell adhesions
      formed by integrins and cadherins receptors are key structures that process
      diverse sources of signals to elicit complex mechanobiological responses. Since
      the nanoscale is the length scale at which molecules interact to relay force and
      information, the understanding of cell adhesions at the nanoscale level is
      important for grasping the inner logics of cellular decision making. Until
      recently, the study of the biological nanoscale has been restricted by available
      molecular and imaging tools. Fortunately, rapid technological advances have
      increasingly opened up the nanoscale realm to systematic investigations. In this
      review, we discuss current insights and key open questions regarding the
      nanoscale structure and function relationship of cell adhesions, focusing on
      recent progresses in characterizing their composition, spatial organization, and
      cytomechanical operation.

PMID- 28754445
TI  - Predictive Power of Distal Radial Metaphyseal Tenderness for Diagnosing Occult
      Fracture.
AB  - PURPOSE: To correlate the physical examination finding of distal radial
      metaphyseal tenderness with plain radiographic and magnetic resonance imaging
      after acute wrist injury to diagnose occult distal radius fractures. We
      hypothesized that persistent distal radial metaphyseal tenderness 2 weeks after
      acute injuries is predictive of an occult fracture. METHODS: Twenty-nine adult
      patients presented, after acute trauma, with distal radial metaphyseal tenderness
      and initial plain radiographs and/or fluoroscopic images that did not show a
      distal radius fracture. Patients were reevaluated clinically and radiographically
      at approximately 2 weeks after initial presentation. Patients with persistent
      distal radial tenderness and negative radiographs underwent magnetic resonance
      imaging to definitively diagnose an occult distal radius fracture. We calculated
      the sensitivity and positive predictive value for persistent distal radial
      metaphyseal tenderness using a 95% confidence interval and standard formulas.
      Both radiographs and magnetic resonance imaging were used as our endpoint
      diagnosis for a distal radius fracture. RESULTS: We diagnosed 28 occult distal
      radius fractures, 8 by follow-up radiograph and 20 by magnetic resonance imaging.
      The positive predictive value for patients who completed the protocol was 96%.
      One patient who did not have an occult distal radius fracture had a fracture of
      the ulnar styloid. CONCLUSIONS: Tenderness of the distal radial metaphysis after
      wrist injury is strongly suggestive of a distal radius fracture despite both
      normal plain radiographs and fluoroscopic images. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Diagnostic III.

PMID- 28754444
TI  - Mitochondrial dynamics: The dynamin superfamily and execution by collusion.
AB  - Distinct dynamin superfamily GTPases catalyze the constant fission and fusion of
      the elaborate mitochondrial networks that navigate the eukaryotic cytoplasm. Long
      believed to be the singular handiwork of dynamin-related protein 1 (Drp1), a
      cytosolic family member that transiently localizes to the mitochondrial surface,
      the execution of mitochondrial fission is now arguably believed to entail
      membrane remodeling events that are initiated upstream of Drp1 by ER-associated
      cytoskeletal networks and completed downstream by the prototypical dynamin,
      dynamin 2 (Dyn2). Recent developments in the field have also placed a sharp focus
      on the membrane microenvironment around the division apparatus and the potential
      facilitatory role of specific lipids in mitochondrial fission. Here, I will
      review current progress, as well as highlight the most visible gaps in knowledge,
      in elucidating the varied functions of the dynamin superfamily in the coordinated
      events of mitochondrial fission and fusion. The essential roles of protein and
      lipid cofactors are also highlighted.

PMID- 28754446
TI  - Selection of reliable reference genes for gene expression studies in Trichoderma
      afroharzianum LTR-2 under oxalic acid stress.
AB  - An appropriate reference gene is required to get reliable results from gene
      expression analysis by quantitative real-time reverse transcription PCR (qRT
      PCR). In order to identify stable and reliable reference genes in Trichoderma
      afroharzianum under oxalic acid (OA) stress, six commonly used housekeeping
      genes, i.e., elongation factor 1, ubiquitin, ubiquitin-conjugating enzyme,
      glyceraldehyde-3-phosphate dehydrogenase, alpha-tubulin, actin, from the
      effective biocontrol isolate T. afroharzianum strain LTR-2 were tested for their
      expression during growth in liquid culture amended with OA. Four in silico
      programs (comparative DeltaCt, NormFinder, geNorm and BestKeeper) were used to
      evaluate the expression stabilities of six candidate reference genes. The
      elongation factor 1 gene EF-1 was identified as the most stably expressed
      reference gene, and was used as the normalizer to quantify the expression level
      of the oxalate decarboxylase coding gene OXDC in T. afroharzianum strain LTR-2
      under OA stress. The result showed that the expression of OXDC was significantly
      up-regulated as expected. This study provides an effective method to quantify
      expression changes of target genes in T. afroharzianum under OA stress.

PMID- 28754447
TI  - MALDI-TOF MS identification and antimicrobial susceptibility testing directly
      from positive enrichment broth.
AB  - A rapid preparation procedure was validated for MALDI-TOF MS identification
      followed by an antimicrobial susceptibility testing directly from a non-selective
      enrichment broth of sterile fluid samples associated with negative classical
      cultures. This method can be easily integrated in the laboratory routine allowing
      precious time gain for microbe identification and subsequent adequate treatment
      initiation.

PMID- 28754448
TI  - Evaluation of OMNIgene(r)*SPUTUM for tuberculosis sample processing and liquid
      culture at a hospital laboratory in India.
AB  - This preliminary evaluation examined the reagent OMNIgene(r)*SPUTUM (OM-S) as a
      tool to eliminate NaOH/NALC processing prior to Middlebrook liquid culture for
      Mycobacterium tuberculosis (MTb). Twenty-seven manually split samples (OM-S
      treated vs. NaOH/NALC) showed 100% agreement: 81.5% MTb-positive and 18.5% MTb
      negative. On average, OM-S-treated specimens required 1.2 additional days to
      culture positivity.

PMID- 28754449
TI  - The role of NADPH oxidases in diabetic cardiomyopathy.
AB  - Systemic changes during diabetes such as high glucose, dyslipidemia, hormonal
      changes and low grade inflammation, are believed to induce structural and
      functional changes in the cardiomyocyte associated with the development of
      diabetic cardiomyopathy. One of the hallmarks of the diabetic heart is increased
      oxidative stress. NADPH-oxidases (NOXs) are important ROS-producing enzymes in
      the cardiomyocyte mediating both adaptive and maladaptive changes in the heart.
      NOXs have been suggested as a therapeutic target for several diabetic
      complications, but their role in diabetic cardiomyopathy is far from elucidated.
      In this review we aim to provide an overview of the current knowledge regarding
      the understanding of how NOXs influences cardiac adaptive and maladaptive
      processes in a "diabetic milieu". This article is part of a Special issue
      entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited
      by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.

PMID- 28754450
TI  - Pathogenesis of biliary fibrosis.
AB  - Chronic cholestatic liver diseases such as primary biliary cholangitis (PBC) and
      primary sclerosing cholangitis (PSC) are associated with active hepatic
      fibrogenesis, and, ultimately, to the development of cirrhosis. However, the
      precise relationship between cholestasis, in its broad meaning, and liver tissue
      fibrosis is still poorly defined. Fibrogenesis is currently viewed as a dynamic
      process that appears strictly related to the extent and duration of parenchymal
      injury. This relationship is clearly evident in the presence of reiterative
      hepatocellular necrosis due to viral infection or alcohol abuse. It appears that
      "pure" intralobular intrahepatic cholestasis secondary to biliary secretory
      failure of the hepatocyte, in absence of hepatocellular damage, lobular
      inflammation and bile duct damage and/or proliferation, is not associated with
      marked and/or progressive liver tissue fibrosis. In contrast, marked and
      progressive liver tissue fibrosis always follows liver diseases characterized by
      chronic inflammatory bile duct damage as seen in PBC and PSC or chronic
      mechanical obstruction of the biliary tree. Overall, the fibrogenic process in
      these clinical conditions appears to be related to a more complex interaction
      between immune/inflammatory mechanisms, cytokine networks and the derangement of
      the homeostasis between epithelial and mesenchymal cells. The elucidation of
      these mechanisms is indeed crucial for the identification of potential diagnostic
      and therapeutic targets.

PMID- 28754451
TI  - Role of inflammation and proinflammatory cytokines in cholangiocyte
      pathophysiology.
AB  - Cholangiocytes, the epithelial cells lining the bile ducts, are an important
      subset of liver cells. They are involved in the modification of bile volume and
      composition, and respond to endogenous and exogenous stimuli. Along the biliary
      tree, two different kinds of cholangiocytes exist: small and large
      cholangiocytes. Each type has different features and biological role in
      physiologic and pathologic conditions, and their immunobiology is important for
      understanding biliary diseases. Cholangiocytes provide the first line of defence
      against luminal microbes in the hepatobiliary system. Indeed, they express a
      variety of pattern recognition receptors and may start an antimicrobial defence
      activating a set of intracellular signalling cascades. In response to injury,
      cholangiocytes that are normally quiescent become reactive and acquire a
      neuroendocrine-like phenotype with the release of proinflammatory mediators and
      antimicrobial peptides, which support biliary epithelial integrity. These
      molecules act in an autocrine/paracrine manner to modulate cholangiocyte biology
      and determine the evolution of biliary damage. Failure or dysregulation of such
      mechanisms may influence the progression of cholangiopathies, a group of diseases
      that selectively target biliary cells. In this review, we focus on the response
      of cholangiocytes in inflammatory conditions, with a particular focus on the
      mechanism driving cholangiocytes adaptation to damage. This article is part of a
      Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus
      Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

PMID- 28754452
TI  - An abnormal TRPV4-related cytosolic Ca2+ rise in response to uniaxial stretch in
      induced pluripotent stem cells-derived cardiomyocytes from dilated cardiomyopathy
      patients.
AB  - Dilated cardiomyopathy (DCM) is cardiac disease characterized by increased left
      ventricular chamber volume and decreased systolic function. DCM patient-specific
      human induced-pluripotent stem cells-derived cardiomyocytes (DCM-hiPSC-CMs) were
      generated. We found that uniaxial stretch elicited a cytosolic [Ca2+]i rise in
      hiPSC-CMs. Compared to control-hiPSC-CMs, DCM-hiPSC-CMs displayed a greater
      magnitude of [Ca2+]i responses to the cell stretch of 10-15% elongation in
      length. This stretch-induced [Ca2+]i rise was abolished by removal of
      extracellular Ca2+ and markedly attenuated by TRPV4 inhibitors HC-067047 and RN
      1734. Application of nifedipine and tranilast also reduced the [Ca2+]i response
      but to a lesser degree. Moreover, the augmented [Ca2+]i was decreased by
      cytochalasin D treatment. Taken together, our study for the first time
      demonstrated an abnormal TRPV4-related mechanosensitive Ca2+ signaling in DCM
      hiPSC-CMs.

PMID- 28754453
TI  - Pathophysiologic implications of innate immunity and autoinflammation in the
      biliary epithelium.
AB  - The most studied physiological function of biliary epithelial cells
      (cholangiocytes) is to regulate bile flow and composition, in particular the
      hydration and alkalinity of the primary bile secreted by hepatocytes. After
      almost three decades of studies it is now become clear that cholangiocytes are
      also involved in epithelial innate immunity, in inflammation, and in the
      reparative processes in response to liver damage. An increasing number of
      evidence highlights the ability of cholangiocyte to undergo changes in phenotype
      and function in response to liver damage. By participating actively to the immune
      and inflammatory responses, cholangiocytes represent a first defense line against
      liver injury from different causes. Indeed, cholangiocytes express a number of
      receptors able to recognize pathogen- or damage-associated molecular patterns
      (PAMPs/DAMPs), such as Toll-like receptors (TLR), which modulate their pro
      inflammatory behavior. Cholangiocytes can be both the targets and the initiators
      of the inflammatory process. Derangements of the signals controlling these
      mechanisms are at the basis of the pathogenesis of different cholangiopathies,
      both hereditary and acquired, such as cystic fibrosis-related liver disease and
      sclerosing cholangitis. This article is part of a Special Issue entitled:
      Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni,
      Nicholas LaRusso and Peter Jansen.

PMID- 28754454
TI  - Clinical spectra of neuromuscular manifestations in patients with lipodystrophy:
      A multicenter study.
AB  - Lipodystrophy is a heterogeneous group of disorders characterized by loss of
      adipose tissue. Here, we report on clinical spectra of neuromuscular
      manifestations of Turkish patients with lipodystrophy. Seventy-four patients with
      lipodystrophy and 20 healthy controls were included. Peripheral sensorimotor
      neuropathy was a common finding (67.4%) in lipodystrophic patients with diabetes.
      Neuropathic foot ulcers were observed in 4 patients. Drop foot developed in 1
      patient with congenital generalized lipodystrophy type 1. Muscle symptoms and
      hypertrophy were consistent findings in congenital generalized lipodystrophy
      (21/21) and familial partial lipodystrophy (25/34); on the other hand, overt
      myopathy with elevated creatine kinase activity was a distinctive characteristic
      of congenital generalized lipodystrophy type 4. Muscle biopsies revealed
      myopathic changes at different levels. Accumulation of triglycerides was observed
      which contributes to insulin resistance. All patients with congenital generalized
      lipodystrophy suffered from tight Achilles tendons at various levels. Scoliosis
      was observed in congenital generalized lipodystrophy type 4 (2/2) and familial
      partial lipodystrophy type 2 (2/17). Atlantoaxial instability was unique to
      congenital generalized lipodystrophy type 4 (2/2). Bone cysts were detected in
      congenital generalized lipodystrophy type 1 (7/10) and congenital generalized
      lipodystrophy type 2 (2/8). Our study suggests that lipodystrophies are
      associated with a wide spectrum of neuromuscular abnormalities.

PMID- 28754456
TI  - HDL Cholesterol, LDL Cholesterol, and Triglycerides as Risk Factors for CKD: A
      Mendelian Randomization Study.
AB  - BACKGROUND: High-density lipoprotein (HDL) cholesterol, low-density lipoprotein
      (LDL) cholesterol, and triglyceride concentrations are heritable risk factors for
      vascular disease, but their role in the progression of chronic kidney disease
      (CKD) is unclear. STUDY DESIGN: 2-sample Mendelian randomization analysis of data
      derived from the largest published lipid and CKD studies. SETTING & PARTICIPANTS:
      Effect of independent genetic variants significantly associated with lipid
      concentrations was obtained from the Global Lipids Genetics Consortium
      (n=188,577), and the effect of these same variants on estimated glomerular
      filtration rate (eGFR), CKD (defined as eGFR<60mL/min/1.73m2), and albuminuria
      was obtained from the CKD Genetics Consortium (n=133,814). FACTOR: Using
      conventional, multivariable, and Egger Mendelian randomization approaches, we
      assessed the causal association between genetically determined lipid
      concentrations and kidney traits. OUTCOME: eGFR, dichotomous
      eGFR<60mL/min/1.73m2, and albuminuria. RESULTS: In multivariable analysis, a 17
      mg/dL higher HDL cholesterol concentration was associated with an 0.8% higher
      eGFR (95% CI, 0.4%-1.3%; P=0.004) and lower risk for eGFR<60mL/min/1.73m2 (OR,
      0.85; 95% CI, 0.77-0.93; P<0.001), while Egger analysis showed no evidence of
      pleiotropy. There was no evidence for a causal relationship between LDL
      cholesterol concentration and any kidney disease measure. Genetically higher
      triglyceride concentrations appeared associated with higher eGFRs, but this
      finding was driven by a single pleiotropic variant in the glucokinase regulator
      gene (GCKR). After exclusion, genetically higher triglyceride concentration was
      not associated with any kidney trait. LIMITATIONS: Individual patient-level
      phenotype and genotype information were unavailable. CONCLUSIONS: 2-sample
      Mendelian randomization analysis of data from the largest lipid and CKD cohorts
      supports genetically higher HDL cholesterol concentration as causally associated
      with better kidney function. There was no association between genetically altered
      LDL cholesterol or triglyceride concentration and kidney function. Further
      analysis of CKD outcomes in HDL cholesterol intervention trials is warranted.

PMID- 28754455
TI  - Lung Function and Incident Kidney Disease: The Atherosclerosis Risk in
      Communities (ARIC) Study.
AB  - BACKGROUND: Reduced lung function is associated with clinical outcomes such as
      cardiovascular disease. However, little is known about its association with
      incident end-stage renal disease (ESRD) and chronic kidney disease (CKD). STUDY
      DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 14,946 participants
      aged 45 to 64 years at baseline (1987-1989) in the Atherosclerosis Risk in
      Communities (ARIC) Study (45.0% men and 25.2% black), with follow-up through
      2012. PREDICTORS: Race- and sex-specific quartiles of percent-predicted forced
      vital capacity (FVC) and the proportion of forced expiratory volume in 1 second
      of expiration to FVC (FEV1/FVC) at baseline determined with spirometry. OUTCOMES:
      Incident ESRD (defined here as renal replacement therapy or death due to CKD) as
      the primary outcome and incident CKD (defined here as ESRD, >=25% decline in
      estimated glomerular filtration rate to a level <60mL/min/1.73m2, or CKD-related
      hospitalizations/deaths) as the secondary outcome. RESULTS: During a median
      follow-up of 23.6 years, 526 (3.5%) participants developed ESRD. After adjusting
      for potential confounders, the cause-specific HR of incident ESRD for the lowest
      (vs highest) quartile was 1.72 (95% CI, 1.31-2.26) for percent-predicted FVC and
      1.33 (95% CI, 1.03-1.73) for FEV1/FVC. Compared to a high-normal lung function
      pattern, a mixed pattern (ie, percent-predicted FVC<80% and FEV1/FVC<70%; 3.4% of
      participants) demonstrated the highest adjusted cause-specific HR of ESRD at 2.28
      (95% CI, 1.50-3.45), followed by the restrictive pattern (ie, percent-predicted
      FVC<80% and FEV1/FVC>=70%; 4.8% of participants) at 2.03 (95% CI, 1.47-2.81),
      obstructive pattern (ie, percent-predicted FVC>=80% and FEV1/FVC<70%; 18.9% of
      participants) at 1.47 (95% CI, 1.09-1.99), and low-normal pattern (ie, percent
      predicted FVC 80%-<100% and FEV1/FVC>=70%, or percent-predicted FVC>=80% and
      FEV1/FVC 70%-<75%; 44.3% of participants) at 1.21 (95% CI, 0.94-1.55). Similar
      associations were seen with incident CKD. LIMITATIONS: Limited number of
      participants with moderate/severe lung dysfunction and spirometry only at
      baseline. CONCLUSIONS: Reduced lung function, particularly lower percent
      predicted FVC, is independently associated with CKD progression. Our findings
      suggest a potential pathophysiologic contribution of reduced lung function to the
      development of CKD and a need for monitoring kidney function in persons with
      reduced lung function.

PMID- 28754457
TI  - Impact of Electronic Acute Kidney Injury (AKI) Alerts With Automated Nephrologist
      Consultation on Detection and Severity of AKI: A Quality Improvement Study.
AB  - BACKGROUND: Several electronic alert systems for acute kidney injury (AKI) have
      been introduced. However, their clinical benefits require further investigation.
      STUDY DESIGN: Before-and-after quality improvement study. SETTING & PARTICIPANTS:
      A tertiary teaching hospital in Korea, which adopted an AKI alert system on June
      1, 2014. Before and after launch of the alert system, 1,884 and 1,309 patients
      with AKI were included in the usual-care and alert groups, respectively. QUALITY
      IMPROVEMENT PLAN: Implementation of an AKI alert system through which clinicians
      could generate automated consultations to the nephrology division for all
      hospitalized patients. OUTCOMES: Primary outcomes included overlooked AKI events,
      defined as not measuring the follow-up creatinine value, and the consultation
      pattern of clinicians. Secondary outcomes were severe AKI events; AKI recovery,
      defined based on the creatinine-based criterion; and patient mortality.
      MEASUREMENTS: ORs for events of overlooked AKI, early consultation, and severe
      AKI were calculated with logistic regression. AKI recovery rate and patient
      mortality were assessed using Cox regression. RESULTS: After introduction of the
      alert system, the odds of overlooked AKI events were significantly lower
      (adjusted OR, 0.40; 95% CI, 0.30-0.52), and the odds of an early consultation
      with a nephrologist were greater (adjusted OR, 6.13; 95% CI, 4.80-7.82). The odds
      of a severe AKI event was reduced after implementation of the alerts (adjusted
      OR, 0.75; 95% CI, 0.64-0.89). Furthermore, the likelihood of AKI recovery was
      improved in the alert group (adjusted HR, 1.70; 95% CI, 1.53-1.88). Mortality was
      not affected by the AKI alert system (adjusted HR, 1.07; 95% CI, 0.68-1.68).
      LIMITATIONS: Possible unreported differences between the alert and usual-care
      groups. CONCLUSIONS: Implementation of the AKI alert system was associated with
      beneficial effects in terms of an improved rate of recovery from AKI. Therefore,
      widespread adoption of such systems could be considered in general hospitals.

PMID- 28754458
TI  - Terfenadine combined with epirubicin impedes the chemo-resistant human non-small
      cell lung cancer both in vitro and in vivo through EMT and Notch reversal.
AB  - The acquired resistance of non-small cell lung cancer (NSCLC) to taxanes
      eventually leads to the recurrence and metastasis of tumours. Thus, the
      development of therapeutic strategies based on the mechanisms by which cells
      acquire resistance to prolong their survival rate in chemotherapy drug treatment
      failure patients are warranted. In this study, we found that the resistant cells
      acquired increased migratory and invasive capabilities, and this transformation
      was correlated with epithelial-mesenchymal transition (EMT) and Notch pathway
      deregulation in the resistant cells. Finally, we reported for the first time that
      terfenadine augmented the effect of epirubicin (EPI) better than Taxol and
      cisplatin (DDP) by inhibiting migration, invasion, and the EMT phenotype, and the
      combination therapy also reversed Notch signalling pathway and enhanced the
      accumulation of fluorescent P-gp substrate rhodamine 123 (Rh123). Similar
      activities of terfenadine on EPI were observed in xenografts. All of our results
      confirmed that terfenadine combined with EPI synergistically inhibits the growth
      and metastatic processes of resistant cells both in vitro and in vivo. Therefore,
      terfenadine or its derivatives are a promising approach for the clinical
      challenge of resistance in patients with advanced NSCLC.

PMID- 28754459
TI  - First description in Europe of the emergence of Enterococcus faecium ST117
      carrying both vanA and vanB genes, isolated in Greece.
AB  - OBJECTIVES: An Enterococcus faecium isolate (Efa-125) carrying both the vanA and
      vanB genes was recovered from a patient with bacteraemia treated in a Greek
      hospital. Since this is the first description in Europe of E. faecium carrying
      both vanA and vanB genes, the isolate was further studied. METHODS:
      Susceptibility to several antibiotics was determined using the VITEK(r)2
      automated system. The isolate was typed by multilocus sequence typing (MLST). To
      define the genetic units of the vanA and vanB genes, the plasmid content of Efa
      125 was analysed by pulsed-field gel electrophoresis (PFGE) of total DNA digested
      with S1 nuclease followed by hybridisation with digoxigenin-labelled vanA and
      vanB probes. In addition, plasmids and chromosomes were sequenced using the
      Illumina MiSeq platform. RESULTS: E. faecium Efa-125 belonged to ST117 and
      expressed resistance both to vancomycin and teicoplanin, with minimum inhibitory
      concentrations (MICs) for both of 256mg/L. The vanA gene was carried on a 29 320
      bp plasmid exhibiting high similarity to pA6981 previously characterised from
      Enterococcus gallinarum A6981, whereas vanB was part of a Tn1549-like transposon
      integrated into the chromosome. Expression of the VanA phenotype was correlated
      with the presence of intact vanZ and vanS genes. CONCLUSIONS: This is the first
      detection in Greece of vanA-vanB genotype/VanA phenotype E. faecium and indicates
      an evolving epidemiology of vancomycin-resistant enterococci.

PMID- 28754460
TI  - Virulence and antimicrobial resistance of Staphylococcus aureus isolated from
      bloodstream infections and pneumonia in Southern Poland.
AB  - OBJECTIVES: Staphylococcus aureus remains the most important cause of infections
      in hospitals and long-term care facilities. The aim of this study was to analyse
      the resistance, virulence, and epidemiological and genetic relationships of S.
      aureus from bloodstream infections (BSIs) and pneumonia from patients in Southern
      Poland. METHODS: All strains were tested for antimicrobial susceptibility using
      the disk diffusion method. Etest was also performed for vancomycin, teicoplanin,
      tigecycline, oxacillin, cefoxitin and penicillin. PCR amplification was used to
      detect selected virulence genes. The genetic similarity of methicillin-resistant
      S. aureus (MRSA) isolates was determined by spa typing and pulsed-field gel
      electrophoresis (PFGE). Using the BURP algorithm and the Ridom SpaServer
      database, spa types were clustered into different clonal complexes (spa-CCs).
      RESULTS AND CONCLUSIONS: MRSA strains were observed at a prevalence of 26.7%, but
      88.6% of hospital-acquired infections were MRSA, with no difference between BSIs
      and pneumonia. The highest resistance was observed to erythromycin and
      tobramycin. None of the strains were resistant to linezolid, glycopeptides or
      tigecycline. The strains had no significant virulence factors and the number of
      virulence genes present did not correlate with the degree of drug resistance.
      PFGE typing showed relatively high diversity of strains. The majority of isolates
      belonged to spa type t003 (CC5).

PMID- 28754461
TI  - Evaluating of fungal contamination in hospital wet cooling systems in Markazi
      province, Central Iran.
AB  - OBJECTIVE: Fungal infections are common complication among hospitalized patients
      especially between who is immunocompromised. Wet cooling systems in the hospital
      environment play a critical role as a source of these infections. The aim of this
      study was survey of wet cooling system of hospitals for fungal contamination in
      Arak city. MATERIALS AND METHODS: This study was conducted during May to
      September of 2016. Sampling was done as random. Samples were obtained from water
      and straw of 84 wet cooling systems of four hospitals in Arak city. Samples were
      cultured in Sabouraud dextrose agar medium contain of chloramphenicol.
      Identification of fungi was performed by Slide culture method. RESULTS: From 84
      wet cooling systems, 32 (38.1%) were contaminated with fungi. The highest fungal
      contamination was found in wards of oncology and CCU. The most prevalent of fungi
      isolated in this study were Aspergillus spp. and Candida spp., respectively.
      CONCLUSION: The findings of this descriptive cross-sectional study clearly
      indicate, in wards of the hospital that used wet cooling systems, there was
      considerable fungal contamination, particularly Aspergillus contamination. These
      results highlight a clear need for greater attention to the use of non-aqueous or
      closed circulation cooling systems, especially where susceptible patients receive
      medical care.

PMID- 28754462
TI  - In vitro susceptibility of Candida albicans clinical isolates to eight antifungal
      agents in Ouagadougou (Burkina Faso).
AB  - INTRODUCTION: In recent years, the infection Candida albicans infection worldwide
      has risen, and the incidence of resistance to traditional antifungal therapies is
      also increasing. The aim of this study was to evaluate in vitro susceptibility of
      C. albicans clinical isolates to eight antifungal agents in Ouagadougou.
      MATERIALS AND METHODS: A cross-sectional study was conducted from January 2013 to
      December 2015 at Yalgado Ouedraogo University Teaching Hospital. Two hundred
      seven strains have been isolated from 347 symptomatic patients received in
      different clinical services. Samples were cultured on Sabouraud Dextrose Agar
      supplemented with Cloramphenicol. Isolates were diagnosed as C. albicans using
      germ tube test, chlamydospore formation on Corn Meal Agar, and Api-Candida test
      (Biomerieux). Antifungal susceptibility testing was performed by disk diffusion
      method and isolates classified as susceptible, susceptible dose-dependent and
      resistant. RESULTS: Three hundred forty-seven (347) patients are included in this
      study. Two hundred and six (206) out of 347 collected samples (59.36%) were found
      positive for C. albicans. The strains were mostly isolated from vulvovaginal
      (49%) and oral infections (40.3%). The highest resistance rates of azoles were
      obtained with fluconazole (66.5%), itraconazole (52.3%) and ketoconazole (22.9%)
      when all clinical isolates were included. The resistance rates of fluconazole,
      itraconazole and ketoconazole remain highest for vulvovaginal and oral isolates.
      The rate of resistance to the polyene amphotericin B was 32.0% for all clinical
      isolates and was 56.4% for vulvovaginal strains. Resistance rate to nystatin was
      6.3% for all clinical isolates. Cross-resistance analysis with data of all
      clinical strains revealed that the incidence of resistance to ketoconazole and
      itraconazole in fluconazole-resistant isolates was significantly higher than
      recorded for fluconazole-susceptible isolates. CONCLUSION: In vitro C. albicans
      antifungal susceptibility test in this study showed relatively high resistance to
      commonly and widely used azoles (fluconazole, ketoconazole). Most C. albicans
      clinical isolates were susceptible to nystatin.

PMID- 28754463
TI  - Author's Reply.

PMID- 28754464
TI  - The utility of routine esophagogastroduodenoscopy before laparoscopic Roux-en-Y
      gastric bypass.
AB  - BACKGROUND: The routine use of esophagogastroduodenoscopy (EGD) before
      laparoscopic Roux-en-y gastric bypass (LRYGB) is debatable. Various studies have
      reported high diagnostic yield of routine EGD before LRYGB to detect pathologies
      that could alter surgical management. However, other studies have found that
      preoperative EGD did not identify significant pathologies that changed clinical
      management; therefore, it is not indicated in asymptomatic patients. OBJECTIVES:
      We aimed to study the utility of routine EGD in patients before LRYGB. SETTING:
      Academic teaching hospital, (Royal Alexandra Hospital, Canada). METHODS: A
      retrospective review of patients undergoing LRYGB with 1 surgeon at our hospital
      from May 2014 to March 2016 was completed. EGD findings were compared with
      surgical gastrojejunal specimen pathology and postoperative complications.
      RESULTS: There were 116 patients who underwent EGD before LRYGB with 113 reported
      EGDs, of which 46.0% were normal, 40.7% had findings that did not result in a
      change of management, and 13.3% had findings resulting in a change of management.
      In the gastrojejunal specimen, 16 patients (14.2%) were found to have chronic
      gastritis. The relative risk of patients having gastrojejunal gastritis was 5.1
      (P<.0005) for patients with gastritis on EGD and 5.1 (P<.0005) for patients with
      Helicobacter pylori infection on EGD. After surgery, 18 patients (15.9%) had
      complications. Preoperative EGD findings were not associated with postoperative
      complications. CONCLUSION: Based on the findings from this study, we recommend
      using less invasive screening in the routine workup of patients awaiting LRYGB
      and reserving EGD for symptomatic patients.

PMID- 28754465
TI  - Evaluation of pharmacokinetic and pharmacodynamic profiles of liposomes for the
      cell type-specific delivery of small molecule drugs.
AB  - Liposome-based drug formulations represent an exciting avenue of research as they
      increase efficacy to toxicity ratios. Current formulations rely on passive
      accumulation to the disease site where drug is taken up by the cells. Ligand
      mediated targeting increases the net accumulation of liposomes, however, an
      unexplored benefit is to potentially refine pharmacodynamics (PD) of a drug
      specifically to different cell types within diseased tissue. As a model system,
      we engineered cardiomyocyte- (I-1) and endothelial-targeted (B-40) liposomes to
      carry a VEGFR2 inhibitor (PTK787), and examined the effect of cell type-specific
      delivery on both pharmacokinetics (PK) and PD. Neovascularization in post
      myocardial infarction was significantly reduced by B-40 liposomes loaded with
      PTK787 as compared to animals injected with I-1 liposomes, and profoundly more as
      compared to free PTK787. This study thus shows that the intraorgan targeting of
      drugs through cell type-specific delivery holds substantial promise towards
      lowering the minimal efficacious dose administered systemically.

PMID- 28754466
TI  - Nanoindentation time-dependent deformation/recovery suggestive of methylglyoxal
      induced glycation in calcified nodules.
AB  - Although empirical findings have indicated increase in bone fracture risk in type
      2 diabetes patients, that has yet to be proven by results obtained at the
      material level. Here, we report evidence showing nanoscale time-dependent
      deformation/recovery of in vitro calcified nodules mimicking bone turnover in
      type 2 diabetes in respect to methylglyoxal (MG)-induced glycation.
      Nanoindentation test results revealed that calcified nodules cultured with MG did
      not show adequate dimensional recovery, despite a large creep rate during
      constant load indentation testing. This lesser recovery is likely based on the
      linear matrix polymerization network formed by advanced glycation end products
      (AGEs) as a secondary product of MG. Since elevated serum MG and abnormal bone
      turnover related to the amount of AGEs are observed in cases of type 2 diabetes,
      this time-dependent behavior may be one of the factors of the bone fracture
      mechanism at the material level in affected patients.

PMID- 28754467
TI  - Rationally designed peptide nanosponges for cell-based cancer therapy.
AB  - A novel type of supramolecular aggregate, named a "nanosponge" was synthesized
      through the interaction of novel supramolecular building blocks with trigonal
      geometry. The cholesterol-(K/D)nDEVDGC)3-trimaleimide unit consists of a trigonal
      maleimide linker to which homopeptides (either K or D) of variable lengths (n=5,
      10, 15, 20) and a consensus sequence for executioner caspases (DEVDGC) are added
      via Michael addition. Upon mixing in aqueous buffer cholesterol-(K)nDEVDGC)3
      trimaleimides and a 1:1 mixture of cholesterol-(K/D)nDEVDGC)3-trimaleimides form
      stable nanosponges, whereas cholesterol-(D)nDEVDGC)3-trimaleimide is unable to
      form supramolecular aggregates with itself. The structure of the novel
      nanosponges was investigated through explicit solvent and then coarse-grained
      molecular dynamics (MD) simulations. The nanosponges are between 80 nm and
      several micrometers in diameters and virtually non-toxic to monocyte/macrophage
      like cells.

PMID- 28754468
TI  - Microhomology-mediated end joining: Good, bad and ugly.
AB  - DNA double-strand breaks (DSBs) are induced by a variety of genotoxic agents,
      including ionizing radiation and chemotherapy drugs for treating cancers. The
      elimination of DSBs proceeds via distinctive error-free and error-prone pathways.
      Repair by homologous recombination (HR) is largely error-free and mediated by
      RAD51/BRCA2 gene products. Classical non-homologous end joining (C-NHEJ) requires
      the Ku heterodimer and can efficiently rejoin breaks, with occasional loss or
      gain of DNA information. Recently, evidence has unveiled another DNA end-joining
      mechanism that is independent of recombination factors and Ku proteins, termed
      alternative non-homologous end joining (A-NHEJ). While A-NHEJ-mediated repair
      does not require homology, in a subtype of A-NHEJ, DSB breaks are sealed by
      microhomology (MH)-mediated base-pairing of DNA single strands, followed by
      nucleolytic trimming of DNA flaps, DNA gap filling, and DNA ligation, yielding
      products that are always associated with DNA deletion. This highly error-prone
      DSB repair pathway is termed microhomology-mediated end joining (MMEJ).
      Dissecting the mechanisms of MMEJ is of great interest because of its potential
      to destabilize the genome through gene deletions and chromosomal rearrangements
      in cells deficient in canonical repair pathways, including HR and C-NHEJ. In
      addition, evidence now suggests that MMEJ plays a physiological role in normal
      cells.

PMID- 28754469
TI  - Long non-coding RNA CCAT1 promotes metastasis and poor prognosis in epithelial
      ovarian cancer.
AB  - In this study, we reported that long non-coding RNA (lncRNA) CCAT1 was
      upregulated in epithelial ovarian cancer (EOC) tissues, and was associated with
      FIGO stage, histological grade, lymph node metastasis and poor survival of EOC
      patients. Multivariate Cox regression analysis showed that CCAT1 was an
      independent prognostic indicator. While CCAT1 downregulation inhibited EOC cell
      epithelial-mesenchymal transition (EMT), migration and invasion, CCAT1
      upregulation promoted EOC cell EMT, migration and invasion. We further identified
      and confirmed that miR-152 and miR-130b were the targets of CCAT1, and CCAT1
      functioned by targeting miR-152 and miR-130b. Subsequently, ADAM17 and WNT1, and
      STAT3 and ZEB1 were confirmed to be the targets of miR-152 and miR-130b,
      respectively, and could be regulated by CCAT1 in EOC cells. Knockdown of anyone
      of these four proteins inhibited EOC cell EMT, migration and invasion. Taken
      together, our study first revealed a critical role of CCAT1-miR-152/miR-130b
      ADAM17/WNT1/STAT3/ZEB1 regulatory network in EOC cell metastasis. These findings
      provide great insights into EOC initiation and progression, and novel potential
      therapeutic targets and biomarkers for diagnosis and prognosis for EOC.

PMID- 28754470
TI  - Oleanane-, ursane-, and quinone methide friedelane-type triterpenoid derivatives:
      Recent advances in cancer treatment.
AB  - Natural pentacyclic triterpenoids (PTs) have been often reported to exhibit a
      wide range of biological activities. Among them, the anticancer and anti
      inflammatory activities are the most studied. Over the last two decades, the
      number of publications reporting the anticancer effects of PTs has risen
      exponentially, reflecting the increasing interest in these natural products for
      the development of new antineoplastic drugs. Among of the most investigated PTs
      regarding their anticancer properties are oleanane-, ursane and friedelane-types,
      including oleanolic, glycyrrhetinic, ursolic and asiatic acids, and celastrol,
      among others. The extensive research in this field shows that the anticancer
      effects of PTs are mediated by several mechanisms, as they modulate a diverse
      range of molecular targets and signaling pathways, involved in cancer cell
      proliferation and survival. Considering the anticancer potential of this class of
      compounds, a number of semisynthetic derivatives has been synthetized aiming to
      improve their therapeutic activity and pharmacokinetic properties, and decrease
      their toxicity. Some of these new semisynthetic derivatives have shown improved
      anticancer activity in various cancer cell lines and animal models compared with
      the parent compound. Moreover, some of these compounds have been assessed in
      clinical trials, proving to be safe for human use. This review updates the most
      recent findings on the semisynthetic derivatives of oleanane-, ursane- and
      quinone methide friedelane-type PTs with anticancer activity. A brief
      introduction concerning the PTs and their anticancer activity is given, and the
      main semisynthetic modifications that have been performed between 2012 and early
      2017 are reviewed and discussed.

PMID- 28754471
TI  - How to train your inhibitor: Design strategies to overcome resistance to
      Epidermal Growth Factor Receptor inhibitors.
AB  - Epidermal Growth Factor Receptor (EGFR) stands out as a key player in the
      development of many cancers. Its dysregulation is associated with a vast number
      of tumors such as non-small-cell lung cancer, colon cancer, head-and-neck cancer,
      breast and ovarian cancer. Being implicated in the development of a number of the
      most lethal cancers worldwide, EGFR has long been considered as a focal target
      for cancer therapies, ever since the FDA approval of "Gefitinib" in 2003 and up
      to the last FDA approved small molecule EGFR kinase inhibitor "Osimertinib" in
      2015. Studies are still going on to find more efficient EGFR inhibitors due to
      the continuous emergence of resistance to the current inhibitors. Cancerous cells
      resist EGFR tyrosine kinase inhibitors (TKIs) through various mechanisms, the
      most commonly reported ones are the T790M mutation and HER2 amplification.
      Therefore, tackling EGFR TKIs-resistant tumors through a multi-targeting approach
      comprising a dual EGFR/HER2 inhibitor that is also capable of inhibiting the
      mutant T790M EGFR is anticipated to overcome drug resistance. In this review, we
      will survey the structural aspects of EGFR family and the structure-activity
      relationship of representative dual EGFR/HER2 inhibitors. To follow, we will
      discuss the structural aspects of the mutation-driven resistance and various
      design strategies to overcome it. Finally, we will review the SAR of exemplary
      irreversible dual EGFR/HER2 inhibitors that can overcome the mutation-driven
      resistance.

PMID- 28754473
TI  - Tobacco Use and Women's Health.

PMID- 28754472
TI  - Exposure to contaminants and nutritional intakes in a French vegetarian
      population.
AB  - The NutriNet Sante study collected, on a voluntary basis, the dietary consumption
      of French vegetarian populations (N = 1766, including 188 vegan individuals) from
      18 to 81 years (18-77 years for the vegan). Taking advantage of the availability
      of contamination data generated in the context of the second French total diet
      study, dietary exposures of French vegetarian populations to several contaminants
      were estimated. Results showed that exposures to persistent organic pollutants
      (PCBs, PCDD/Fs for instance) was dramatically lower than those of the general
      French population due to the non consumption of food of animal origins. On the
      other hand, exposures to phytoestrogens, some mycotoxins (T2 and HT2 toxins) and
      some trace elements (Cd, Al, Sn, Ni) were higher in the vegetarian population
      compared to those of the general population. Despite some limitations of this
      approach (both the consumption study and the total diet study were not aimed to
      estimate dietary exposure of the vegetarian populations), this study showed that
      dietary habits can dramatically influence the exposure of some contaminants.

PMID- 28754474
TI  - Description of Absiella argi gen. nov., sp. nov., and transfer of Eubacterium
      dolichum and Eubacterium tortuosum to the genus Absiella as Absiella dolichum
      comb. nov. and Absiella tortuosum comb. nov.
AB  - Gram-positive, straight or slightly curved rod-shaped bacteria, designated as
      strains N6H1-5T and N6H1-3, were isolated from fecal samples of old dog. The
      analysis of 16S rRNA gene sequences indicated that the isolates belonged to the
      Clostridium cluster XVI and were closely related to Eubacterium dolichum KCTC
      5832T, Eubacterium tortuosum DSM 3987T, Clostridium innocuum KCTC 5183T,
      Allobaculum stecoricanis DSM 13633T, Eubacterium limosum KCTC 3266T, and
      Clostridium butyricum KCTC 1871T, with 94.0%, 93.8%, 92.0%, 84.9%, 80.7%, and
      80.0% sequence similarity, respectively. Chemotaxonomic data supported placement
      of the strains N6H1-5T and N6H1-3 in the new taxon. The strains contained m
      diaminopimelic acid cell wall peptidoglycan; the major polar lipids were
      diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), and glycolipids (GL);
      and the major fatty acids were C18:1cis 9 (30.7%) and C16:0 (17.1%). The
      predominant metabolic end product was lactic acid. The G + C content was 35.8
      mol%. The most closely related species, E. dolichum and E. tortuosum, were also
      assigned to the new taxon, based on the phylogenetic analysis and phenotypic
      data. Thus, the type strain N6H1-5T (=KCTC 15422 = JCM 30884) represents a novel
      genus and species, for which the name Absiella argi gen. nov., sp. nov is
      proposed. It is also proposed that E. dolichum KCTC 5832T and E. tortuosum DSM
      3987T be transferred to this new genus, and named Absiella dolichum comb. nov.
      and Absiella tortuosum comb. nov., respectively.

PMID- 28754475
TI  - Detection of enterotoxin and protease genes among Hungarian clinical Bacteroides
      fragilis isolates.
AB  - Bacteroides fragilis as a commensal bacterium is a member of the human intestinal
      flora, but as an opportunistic pathogen it can cause serious infections as well.
      Some of them, harbouring an enterotoxin gene (bft), may cause diarrhoea mainly in
      young children. Recently it has been shown that a member of C11 proteases called
      fragipain (fpn) can activate the enterotoxin, while C10 protease (bfp) is
      suspected of playing an important role in the invasiveness of the B. fragilis
      isolates. The objective of this study was to investigate the prevalence and
      distribution of the bft isotypes in 200 Hungarian B. fragilis isolates collected
      recently; and in a subset of 72 strains, we wanted to determine the prevalence of
      bfp1-4 and fpn genes in bft-positive and bft-negative strains. Using the MALDI
      TOF MS cfiA identification project file, 19 B. fragilis strains belonging to
      Division II were identified and the presence of the cfiA gene was confirmed by RT
      PCR. Twenty six (13.0%) B. fragilis isolates turned out to be bft gene positive
      by RT-PCR; 20 isolates harboured bft-1 and six bft-2 isotypes, but no bft-3
      isotype containing strains were found. A melting curve analysis and the PCR-RFLP
      were performed to differentiate between the bft-1 and bft-2 isotypes confirmed by
      sequencing. Thirty eight strains harboured bfp1, 58 isolates contained bfp2 gene,
      while 17 isolates proved positive for bfp3. Morever, no bfp4 positive isolate was
      found, and some of the B. fragilis strains tested harboured two or three bfp
      isotypes simultaneously. Among the 26 bft-positive strains, 24 contained the fpn
      gene, which confirms the role of fragipain in the activation of B. fragilis
      enterotoxin. In experiments, a significant negative correlation between fpn and
      cfiA was demonstrated (p < 0.000), a positive correlation was found between bfp2
      and fpn genes (p = 0.0000803), and a negative correlation between bfp2 and cfiA
      genes (p = 0.011).

PMID- 28754476
TI  - Primary Care Providers with More Experience and Stronger Self-Efficacy Beliefs
      Regarding Women Veterans Screen More Frequently for Interpersonal Violence.
AB  - BACKGROUND: Military sexual trauma (MST) and/or intimate partner violence (IPV)
      are common experiences in the growing group of women veterans using the Veterans
      Health Administration health care system. And even though MST screening is
      closely monitored at the facility level, little is known about individual primary
      care provider (PCP) behavior with regard to screening women for MST and IPV.
      OBJECTIVES: To understand how PCP experiences and beliefs regarding women's
      health care influence PCP-reported screening for MST and IPV. RESEARCH DESIGN AND
      PARTICIPANTS: We administered a cross-sectional online survey from September 2014
      through April 2015 (supplemented by a mailed survey between April and May 2015)
      to 281 PCPs in 12 Veterans Health Administration medical centers. MEASURES AND
      ANALYSIS: Surveys measured PCP-reported screening frequency for MST and IPV,
      experience with women veterans, self-efficacy, gender-sensitive beliefs, and
      perceived barriers to providing comprehensive care for women. We used
      multivariable ordered logistic regression analysis to identify correlates of
      screening, weighted for nonresponse and adjusted for clustering. RESULTS: Ninety
      four PCPs (34%) completed the survey. Being a designated women's health provider
      (p < .05) and stronger self-efficacy beliefs about screening women for MST (p <
      .001) were associated with reporting more frequent screening for MST. Being a
      designated women's health provider (p < .01), seeing women patients at least once
      per week (p < .001), and self-efficacy beliefs about screening women for IPV (p <
      .001) were associated with reporting more frequent screening for IPV.
      CONCLUSIONS: Veterans Health Administration initiatives to enhance PCP
      opportunities to screen women veterans for trauma and to strengthen self-efficacy
      beliefs about comprehensive women's health care may increase screening of women
      veterans for MST and IPV.

PMID- 28754477
TI  - Chlorhexidine gel probably reduces the incidence of alveolar osteitis after
      mandibular third-molar extraction.

PMID- 28754478
TI  - Proximal sealing of permanent first molars adjacent to primary second molars with
      active distal caries may help prevent carious lesion development and progression
      after 3 and one-half years.

PMID- 28754479
TI  - Untreated dental caries associated with small worsening of oral health-related
      quality of life in 1- to 3-year-old children.

PMID- 28754480
TI  - Evidence about the type of graft material on long-term implant treatment outcomes
      after maxillary sinus floor augmentation is not sufficient for making clinical
      decisions.

PMID- 28754481
TI  - Repairing class II restorations seems to increase the longevity of direct class
      II restorations, but the benefit may vary substantially depending on the
      operator.

PMID- 28754482
TI  - Patients with compromised oral health-related quality of life experienced an
      improvement when wearing complete dentures fabricated conventionally or using the
      neutral zone concept.

PMID- 28754484
TI  - To promote maintenance or treatment, is that the question?

PMID- 28754483
TI  - Olaparib tablets as maintenance therapy in patients with platinum-sensitive,
      relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double
      blind, randomised, placebo-controlled, phase 3 trial.
AB  - BACKGROUND: Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has
      previously shown efficacy in a phase 2 study when given in capsule formulation to
      all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian
      cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2
      (BRCA1/2) mutation using a tablet formulation of olaparib. METHODS: This
      international, multicentre, double-blind, randomised, placebo-controlled, phase 3
      trial evaluated olaparib tablet maintenance treatment in platinum-sensitive,
      relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at
      least two lines of previous chemotherapy. Eligible patients were aged 18 years or
      older with an Eastern Cooperative Oncology Group performance status at baseline
      of 0-1 and histologically confirmed, relapsed, high-grade serous ovarian cancer
      or high-grade endometrioid cancer, including primary peritoneal or fallopian tube
      cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg
      tablets, twice daily) or matching placebo tablets using an interactive voice and
      web response system. Randomisation was stratified by response to previous
      platinum chemotherapy (complete vs partial) and length of platinum-free interval
      (6-12 months vs >=12 months) and treatment assignment was masked for patients,
      those giving the interventions, data collectors, and data analysers. The primary
      endpoint was investigator-assessed progression-free survival and we report the
      primary analysis from this ongoing study. The efficacy analyses were done on the
      intention-to-treat population; safety analyses included patients who received at
      least one dose of study treatment. This trial is registered with
      ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting
      patients. FINDINGS: Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295
      eligible patients who were randomly assigned to receive olaparib (n=196) or
      placebo (n=99). One patient in the olaparib group was randomised in error and did
      not receive study treatment. Investigator-assessed median progression-free
      survival was significantly longer with olaparib (19.1 months [95% CI 16.3-25.7])
      than with placebo (5.5 months [5.2-5.8]; hazard ratio [HR] 0.30 [95% CI 0.22
      0.41], p<0.0001). The most common adverse events of grade 3 or worse severity
      were anaemia (38 [19%] of 195 patients in the olaparib group vs two [2%] of 99
      patients in the placebo group), fatigue or asthenia (eight [4%] vs two [2%]), and
      neutropenia (ten [5%] vs four [4%]). Serious adverse events were experienced by
      35 (18%) patients in the olaparib group and eight (8%) patients in the placebo
      group. The most common in the olaparib group were anaemia (seven [4%] patients),
      abdominal pain (three [2%] patients), and intestinal obstruction (three [2%]
      patients). The most common in the placebo group were constipation (two [2%]
      patients) and intestinal obstruction (two [2%] patients). One (1%) patient in the
      olaparib group had a treatment-related adverse event (acute myeloid leukaemia)
      with an outcome of death. INTERPRETATION: Olaparib tablet maintenance treatment
      provided a significant progression-free survival improvement with no detrimental
      effect on quality of life in patients with platinum-sensitive, relapsed ovarian
      cancer and a BRCA1/2 mutation. Apart from anaemia, toxicities with olaparib were
      low grade and manageable. FUNDING: AstraZeneca.

PMID- 28754485
TI  - Prevalence and incidence of pressure injuries in pediatric hospitals in the city
      of Sao Paulo, SP, Brazil.
AB  - OBJECTIVE: To identify the incidence and prevalence of pressure injuries (PIs) in
      children admitted to hospitals in the city of Sao Paulo, and assess the
      association between sociodemographic and clinical characteristics with hospital
      acquired pressure injuries (HAPIs). MATERIALS AND METHODS: A total of 543
      children were evaluated, and their sociodemographic and clinical data were
      recorded. Student's t, Wilcoxon, chi-square, and Fisher's exact tests were used
      to assess associations between risk factors and the occurrence of HAPIs. The
      proportion comparison test was used to assess the difference between the
      prevalence assessments performed at 2 different time points. RESULTS: The mean
      prevalence was 7.1% and the mean incidence was 21.8%. Stage 1 PIs totaled 55% of
      the occurrences, followed by deep tissue injury, stage 2 PIs, and unstageable
      PIs. Twenty-five percent of PIs were associated with the use of medical devices.
      The sociodemographic characteristics significantly associated with HAPIs were
      white skin color and the absence of a parent or guardian as the patient's
      companion, whereas the clinical characteristics most significantly associated
      with HAPIs were hospitalization time greater than 30 days, enteral nutrition
      pathway, a chronic illness of the central nervous system, vasomotor medication,
      and mechanical ventilation (p < 0.05). CONCLUSION: The prevalence of PIs among
      pediatric patients admitted to hospitals in Sao Paulo was similar to, and the
      incidence was higher than the reported international rates. Patients not
      accompanied by a parent, hospitalized for longer periods and in critical
      condition were those most affected by PIs.

PMID- 28754486
TI  - What is the yield of breast MRI in the assessment of palpable breast findings?
AB  - AIM: To examine the contribution of magnetic resonance imaging (MRI) to
      characterise palpable breast masses after conventional imaging was found to be
      non-contributory. MATERIALS AND METHODS: The breast MRI database was reviewed for
      studies performed between January 2010 and December 2015 for the clinical
      indication of palpable breast finding with negative standard imaging. Medical
      files were reviewed for demographic data, clinical information, radiology, and
      pathology reports. Benign versus malignant outcomes were determined at
      histopathology or a minimum of 12 month follow-up. RESULTS: Investigation of
      palpable breast finding was the clinical indication for 167 of 7,782 (2%)
      examinations. Thirty-two (19%) women in the study had positive MRI findings. Most
      (20, 63%) findings corresponded to the palpable area, resulting in three
      carcinomas being diagnosed. Only one carcinoma required MRI-guided biopsy for
      diagnosis. Eighteen women with negative MRI underwent ultrasound-guided biopsy
      from the palpable area, which resulted in a diagnosis of one carcinoma. One
      carcinoma was incidentally detected in another location. Within the present
      population, the sensitivity for detecting malignancy was 80%, specificity 78%,
      negative predictive value 99%, and positive predictive value 13%. CONCLUSIONS:
      Although cancer was found in four cases in the palpable area, the biopsy was
      directed using MRI in only one case. A new palpable finding with non-contributory
      standard imaging should prompt a needle-guided biopsy and not further evaluation
      using MRI.

PMID- 28754487
TI  - Recombinant Gallid herpesvirus 2 with interrupted meq genes confers safe and
      efficacious protection against virulent field strains.
AB  - Gallid herpesvirus 2 (GaHV-2) continuously evolves, which reduces the
      effectiveness of existing vaccines. To construct new GaHV-2 candidate vaccines,
      LMS, which is a virulent GaHV-2 field strain isolated from diseased chicken
      flocks in Southwest China in 2007, was modified such that both copies of its meq
      oncogene were partially deleted. The resulting virus, i.e., rMSDeltameq, was
      characterized using PCR and sequencing. To evaluate the safety and protective
      efficacy of rMSDeltameq, specific pathogen-free (SPF) chickens were inoculated
      with 2000 plaque forming units (pfu) and 20,000pfu of rMSDeltameq immediately
      after hatching. All birds grew well during the experimental period, and none of
      the challenged chickens developed Marek's disease-associated lymphoma. In
      addition, the rMSDeltameq- and CVI988/Rispens-vaccinated SPF chickens were
      challenged with 1000 pfu and 5000 pfu of the representative virulent GaHV-2 Md5
      strain and 1000 pfu of the variant GaHV-2 strains LCC or LTS. The results showed
      that the rMSDeltameq strain provided complete protection, which was similar to
      that provided by the CVI988/Rispens vaccine (protective index (PI) of 95.5) when
      challenged with a conventional dose of the Md5 strain. However, rMSDeltameq
      provided a PI of 90.9 when challenged with 5000 pfu of the Md5 strain, which was
      significantly higher than that provided by the CVI988/Rispens vaccine (54.5).
      rMSDeltameq provided a PI of 86.4 against LCC, which was equal to that provided
      by the CVI988/Rispens vaccine (81.8). In addition, rMSDeltameq provided a PI of
      100 against LTS, which was significantly higher than that provided by the
      CVI988/Rispens vaccine (68.2). Altogether, the rMSDeltameq virus provided
      efficient protection against representative and variant GaHV-2 strains. In
      conclusion, the rMSDeltameq virus is a safe and effective vaccine candidate for
      the prevention of Marek's disease and is effective against the Chinese variant
      GaHV-2 strains.

PMID- 28754488
TI  - Survey of distribution of seasonal influenza vaccine doses in 201 countries (2004
      2015): The 2003 World Health Assembly resolution on seasonal influenza
      vaccination coverage and the 2009 influenza pandemic have had very little impact
      on improving influenza control and pandemic preparedness.
AB  - There is no global monitoring system for influenza vaccination coverage, making
      it difficult to assess progress towards the 2003 World Health Assembly (WHA)
      vaccination coverage target. In 2008, the IFPMA Influenza Vaccine Supply
      International Task Force (IVS) developed a survey method to assess the global
      distribution of influenza vaccine doses as a proxy for vaccination coverage
      rates. The latest dose distribution data for 2014 and 2015 was used to update
      previous analyses. Data were confidentially collected and aggregated by the IFPMA
      Secretariat, and combined with previous IFPMA IVS survey data (2004-2013). Data
      were available from 201 countries over the 2004-2015 period. A "hurdle" rate was
      defined as the number of doses required to reach 15.9% of the population in 2008.
      Overall, the number of distributed doses progressively increased between 2004 and
      2011, driven by a 150% increase in AMRO, then plateaued. One percent fewer doses
      were distributed in 2015 than in 2011. Twenty-three countries were above the
      hurdle rate in 2015, compared to 15 in 2004, but distribution was highly uneven
      in and across all WHO regions. Three WHO regions (AMRO, EURO and WPRO) accounted
      for about 95% of doses distributed. But in EURO and WPRO, distribution rates in
      2015 were only marginally higher than in 2004, and in EURO there was an overall
      downward trend in dose distribution. The vast majority of countries cannot meet
      the 2003WHA coverage targets and are inadequately prepared for a global influenza
      pandemic. With only 5% of influenza vaccine doses being distributed to 50% of the
      world's population, there is urgency to redress the gross inequities in disease
      prevention and in pandemic preparedness. The 2003WHA resolution must be reviewed
      and revised and a call issued for the renewed commitment of Member States to
      influenza vaccination coverage targets.

PMID- 28754489
TI  - Unseen fearful faces facilitate visual discrimination in the intact field.
AB  - Implicit visual processing of emotional stimuli has been widely investigated
      since the classical studies on affective blindsight, in which patients with
      primary visual cortex lesions showed discriminatory abilities for unseen
      emotional stimuli in the absence of awareness. In addition, more recent evidence
      from hemianopic patients showed response facilitation and enhanced early visual
      encoding of seen faces, only when fearful faces were presented concurrently in
      the blind field. However, it is still unclear whether unseen fearful faces
      specifically facilitate visual processing of facial stimuli, or whether the
      facilitatory effect constitutes an adaptive mechanism prioritizing the visual
      analysis of any stimulus. To test this question, we tested a group of hemianopic
      patients who perform at chance in forced-choice discrimination tasks of stimuli
      in the blind field. Patients performed a go/no-go task in which they were asked
      to discriminate simple visual stimuli (Gabor patches) presented in their intact
      field, while fearful, happy and neutral faces were concurrently presented in the
      blind field. The results showed a reduction in response times to the Gabor
      patches presented in the intact field, when fearful faces were concurrently
      presented in the blind field, but only in patients with left hemispheric lesions.
      No facilitatory effect was observed in patients with right hemispheric lesions.
      These results suggest that unseen fearful faces are implicitly processed and can
      facilitate the visual analysis of simple visual stimuli presented in the intact
      field. This effect might be subserved by activity in the spared colliculo
      amygdala-extrastriate pathway that promotes efficient visual analysis of the
      environment and rapid execution of defensive responses. Such a facilitation is
      observed only in patients with left lesions, favouring the hypothesis that the
      right hemisphere mediates implicit visual processing of fear signals.

PMID- 28754490
TI  - The effect of category learning on attentional modulation of visual cortex.
AB  - Learning about visual object categories causes changes in the way we perceive
      those objects. One likely mechanism by which this occurs is the application of
      attention to potentially relevant objects. Here we test the hypothesis that
      category membership influences the allocation of attention, allowing attention to
      be applied not only to object features, but to entire categories. Participants
      briefly learned to categorize a set of novel cartoon animals after which EEG was
      recorded while participants distinguished between a target and non-target
      category. A second identical EEG session was conducted after two sessions of
      categorization practice. The category structure and task design allowed
      parametric manipulation of number of target features while holding feature
      frequency and category membership constant. We found no evidence that category
      membership influenced attentional selection: a postero-lateral negative
      component, labeled the selection negativity/N250, increased over time and was
      sensitive to number of target features, not target categories. In contrast, the
      right hemisphere N170 was not sensitive to target features. The P300 appeared
      sensitive to category in the first session, but showed a graded sensitivity to
      number of target features in the second session, possibly suggesting a transition
      from rule-based to similarity based categorization.

PMID- 28754491
TI  - Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio
      oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled
      crossover trial.
AB  - BACKGROUND: Hereditary angio-oedema is a recurrent, oedematous disorder caused by
      deficiency of functional C1 inhibitor. Infusions of plasma-derived C1 esterase
      inhibitor deter attacks of hereditary angio-oedema, but the prophylactic effect
      of recombinant human C1 esterase inhibitor has not been rigorously studied. We
      aimed to assess the efficacy of recombinant human C1 esterase inhibitor for
      prophylaxis of hereditary angio-oedema. METHODS: We conducted this phase 2,
      multicentre, randomised, double-blind, placebo-controlled crossover trial at ten
      centres in Canada, the Czech Republic, Israel, Italy, Macedonia, Romania, Serbia,
      and the USA. We enrolled patients aged 13 years or older with functional C1
      inhibitor concentrations of less than 50% of normal and a history of four or more
      attacks of hereditary angio-oedema per month for at least 3 months before study
      initiation. Patients were randomly assigned centrally (1:1:1:1:1:1), via an
      interactive response technology system with fixed allocation, to receive one of
      six treatment sequences. During each sequence, patients received intravenous
      recombinant human C1 esterase inhibitor (50 IU/kg; maximum 4200 IU) twice weekly,
      recombinant human C1 esterase inhibitor once weekly and placebo once weekly, and
      placebo twice weekly, each for 4 weeks with a 1 week washout period between
      crossover. All patients, investigators, and study personnel who participated in
      patient care were masked to group allocation during the study. The primary
      efficacy endpoint was the number of attacks of hereditary angio-oedema observed
      in each 4 week treatment period. Attack symptoms were recorded daily. The primary
      efficacy analysis was done in the intention-to-treat population. Safety was
      assessed in all patients who received at least one injection of study medication.
      This study is registered with ClinicalTrials.gov, number NCT02247739. FINDINGS:
      Between Dec 29, 2014, and May 3, 2016, we enrolled 35 patients, of whom 32 (91%)
      underwent randomisation (intention-to-treat population) and 26 (81%) completed
      the study. The mean number of attacks of hereditary angio-oedema over 4 weeks was
      significantly reduced with recombinant human C1 esterase inhibitor twice weekly
      (2.7 attacks [SD 2.4]) and once weekly (4.4 attacks [3.2]) versus placebo (7.2
      attacks [3.6]), with mean differences of -4.4 attacks (p<0.0001) and -2.8 attacks
      (p=0.0004), respectively. We recorded adverse events in ten (34%) of 29 patients
      given twice-weekly recombinant human C1 esterase inhibitor, 13 (45%) of 29
      patients given the once-weekly regimen, and eight (29%) of 28 patients given
      placebo. Headache (twice-weekly treatment) and nasopharyngitis (once-weekly
      treatment) were the most common adverse events. Two (7%) adverse events (fatigue
      and headache) were deemed possibly related to treatment with recombinant human C1
      esterase inhibitor, but both resolved without additional treatment. No thrombotic
      or thromboembolic events, systemic allergic reactions (including anaphylaxis), or
      neutralising antibodies were reported. INTERPRETATION: Prophylaxis with
      recombinant human C1 esterase inhibitor provided clinically relevant reductions
      in frequency of hereditary angio-oedema attacks and was well tolerated. In view
      of the pharmacokinetic profile of recombinant human C1 esterase inhibitor, our
      results suggest that efficacy of C1-inhibitor replacement therapy might not be a
      direct function of plasma trough concentrations of C1 inhibitor. FUNDING:
      Pharming Technologies.

PMID- 28754492
TI  - The French emergency medical services after the Paris and Nice terrorist attacks:
      what have we learnt?

PMID- 28754493
TI  - Is there a future for mRNAs as viral vaccines?

PMID- 28754494
TI  - Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open
      label, non-randomised, prospective, first-in-human phase 1 clinical trial.
AB  - BACKGROUND: Vaccines based on mRNA coding for antigens have been shown to be safe
      and immunogenic in preclinical models. We aimed to report results of the first-in
      human proof-of-concept clinical trial in healthy adults of a prophylactic mRNA
      based vaccine encoding rabies virus glycoprotein (CV7201). METHODS: We did an
      open-label, uncontrolled, prospective, phase 1 clinical trial at one centre in
      Munich, Germany. Healthy male and female volunteers (aged 18-40 years) with no
      history of rabies vaccination were sequentially enrolled. They received three
      doses of CV7201 intradermally or intramuscularly by needle-syringe or one of
      three needle-free devices. Escalating doses were given to subsequent cohorts, and
      one cohort received a booster dose after 1 year. The primary endpoint was safety
      and tolerability. The secondary endpoint was to determine the lowest dose of
      CV7201 to elicit rabies virus neutralising titres equal to or greater than the
      WHO-specified protective antibody titre of 0.5 IU/mL. The study is continuing for
      long-term safety and immunogenicity follow-up. This trial is registered with
      ClinicalTrials.gov, number NCT02241135. FINDINGS: Between Oct 21, 2013, and Jan
      11, 2016, we enrolled and vaccinated 101 participants with 306 doses of mRNA (80
      640 MUg) by needle-syringe (18 intradermally and 24 intramuscularly) or needle
      free devices (46 intradermally and 13 intramuscularly). In the 7 days post
      vaccination, 60 (94%) of 64 intradermally vaccinated participants and 36 (97%) of
      37 intramuscularly vaccinated participants reported solicited injection site
      reactions, and 50 (78%) of 64 intradermally vaccinated participants and 29 (78%)
      of 37 intramuscularly vaccinated participants reported solicited systemic adverse
      events, including ten grade 3 events. One unexpected, possibly related, serious
      adverse reaction that occurred 7 days after a 640 MUg intramuscular dose resolved
      without sequelae. mRNA vaccination by needle-free intradermal or intramuscular
      device injection induced virus neutralising antibody titres of 0.5 IU/mL or more
      across dose levels and schedules in 32 (71%) of 45 participants given 80 MUg or
      160 MUg CV7201 doses intradermally and six (46%) of 13 participants given 200 MUg
      or 400 MUg CV7201 doses intramuscularly. 1 year later, eight (57%) of 14
      participants boosted with an 80 MUg needle-free intradermal dose of CV7201
      achieved titres of 0.5 IU/mL or more. Conversely, intradermal or intramuscular
      needle-syringe injection was ineffective, with only one participant (who received
      320 MUg intradermally) showing a detectable immune response. INTERPRETATION: This
      first-ever demonstration in human beings shows that a prophylactic mRNA-based
      candidate vaccine can induce boostable functional antibodies against a viral
      antigen when administered with a needle-free device, although not when injected
      by a needle-syringe. The vaccine was generally safe with a reasonable
      tolerability profile. FUNDING: CureVac AG.

PMID- 28754495
TI  - Recombinant human C1 esterase inhibitor for hereditary angio-oedema.

PMID- 28754496
TI  - Single-cell RNA sequencing: Technical advancements and biological applications.
AB  - Cells are the basic building blocks of organisms and each cell is unique. Single
      cell RNA sequencing has emerged as an indispensable tool to dissect the cellular
      heterogeneity and decompose tissues into cell types and/or cell states, which
      offers enormous potential for de novo discovery. Single-cell transcriptomic
      atlases provide unprecedented resolution to reveal complex cellular events and
      deepen our understanding of biological systems. In this review, we summarize and
      compare single-cell RNA sequencing technologies, that were developed since 2009,
      to facilitate a well-informed choice of method. The applications of these methods
      in different biological contexts are also discussed. We anticipate an ever
      increasing role of single-cell RNA sequencing in biology with further improvement
      in providing spatial information and coupling to other cellular modalities. In
      the future, such biological findings will greatly benefit medical research.

PMID- 28754497
TI  - Ultrasonography Improves Glycemic Control by Detecting Insulin-Derived Localized
      Amyloidosis.
AB  - We examined the feasibility of ultrasound diagnosis of insulin-derived localized
      amyloidosis (IDLA). In addition to ultrasound detectability and findings, the
      insulin absorption rate, insulin dosage and hemoglobin A1c (HbA1c) levels before
      and after shifting the insulin injection site were investigated for 22 cases of
      IDLA. The detectability of IDLA on ultrasound was 100%; 59.1% was palpable lumps
      and 40.9% was not palpable. The palpable type had lower echo intensity and were
      harder than the non-palpable type. Blood flow decreased in IDLA, especially in
      the palpable type. IDLA, especially the palpable type, had a low insulin
      absorption rate. HbA1c level and insulin dosage decreased after shifting the
      injection site. The palpable type had more insulin reduction than the non
      palpable type. Characteristic ultrasound images of IDLA were acquired. As the non
      palpable type could be identified by ultrasound, its diagnosis encourages
      changing the insulin injection site; hence, ultrasound diagnosis of IDLA can
      enhance insulin treatment.

PMID- 28754498
TI  - A Pragmatic Introduction of Mindfulness in a Continuing Education Setting:
      Exploring Personal Experience, Bridging to Professional Practice.
AB  - CONTEXT: Continuing Medical Education and Continuing Professional Education
      (CME/CPE) provide a context through which to introduce practicing Healthcare
      Professionals (HCPs) to emerging mind/body approaches. OBJECTIVE: To introduce
      mindfulness to practicing HCPs for application in their practice through an
      experiential CME/CPE session. DESIGN: This descriptive study included surveys
      administered in the context of a CME/CPE session at professional meetings, as
      well as a three-month follow-up survey. SETTING: The mindfulness session was
      administered at 5 state-wide professional CME/CPE meetings throughout Ohio.
      PARTICIPANTS: Participants practicing dieticians, nurses, psychologists, and
      smoking cessation educators, among others. INTERVENTION: A brief experiential
      introduction to mindfulness and the potential application within healthcare.
      MEASURES: These included participant's prior awareness and use of Complementary
      and Alternative Medicine (CAM) techniques, and subsequent likelihood of
      investigating these modalities further for personal and professional use.
      RESULTS: 64.4% of HCPs had used CAM for personal use and 49.3% had used CAM in
      their clinical practice, while 74.8% of HCPs had been asked by patients about CAM
      and 84.3% of the HCPs perceived a need for more education on CAM.94.79% of
      respondents reported likeliness to investigate mindfulness for personal use and
      92.58% for professional use. CONCLUSION: A brief mindfulness intervention for
      HCPs utilizing a CME/CPE mechanism is a feasible and effective way to introduce
      HCPs to a mind/body therapy such as mindfulness. CME/CPE instruction ensures that
      the information provided is in line with evidenced based practice and an
      experiential component of the instruction demonstrates for the HCP an appropriate
      use of CAM with patients.

PMID- 28754499
TI  - Fructose induced neurogenic hypertension mediated by overactivation of p38 MAPK
      to impair insulin signaling transduction caused central insulin resistance.
AB  - Type 2 diabetes are at a high risk of complications related to hypertension, and
      reports have indicated that insulin levels may be associated with blood pressure
      (BP). Fructose intake has recently been reported to promote insulin resistance
      and superoxide formation. The aim of this study is to investigate whether
      fructose intake can enhance superoxide generation and impair insulin signaling in
      the NTS and subsequently elevate BP in rats with fructose-induced hypertension.
      Treatment with fructose for 4 weeks increased the BP, serum fasting insulin,
      glucose, homeostatic model assessment-insulin resistance, and triglyceride levels
      and reduced the serum direct high-density lipoprotein level in the fructose
      group. The Tempol treatment recovered the fructose-induced decrease in nitric
      oxide production in the NTS. Immunoblotting and immunofluorescence analyses
      further showed that fructose increased the p38- and fructose-induced
      phosphorylation of insulin receptor substrate 1 (IRS1S307) and suppressed AktS473
      and neuronal nitric oxide synthase phosphorylation. Similarly, fructose was able
      to impair insulin sensitivity and increase insulin levels in the NTS. Fructose
      intake also increased the production of superoxide in the NTS. The results of
      this study suggest that fructose might induce central insulin resistance and
      elevate BP by enhancing superoxide production and activating p38 phosphorylation
      in the NTS.

PMID- 28754500
TI  - Maternal prenatal blood mercury is not adversely associated with offspring IQ at
      8 years provided the mother eats fish: A British prebirth cohort study.
AB  - BACKGROUND: Conflicting evidence concerning possible harm from mercury (Hg) in
      regard to offspring cognition if the woman eats fish has prompted this study to
      examine evidence from a British pre-birth cohort to investigate the relationship
      between the two. METHODS: Pregnant women (median prenatal blood mercury
      1.86MUg/L) resident in the study area with delivery between April 1991 and
      December 1992 were followed up and verbal, performance and total intelligence
      quotient (IQ) of 2062 offspring were measured at age 8. Analysis treated IQ as
      (a) continuous and (b) the lowest 25% of the distribution. Multiple and logistic
      regression analyses took account of social and demographic variables.
      Stratification considered children of fish eaters separately. RESULTS: Before
      adjustment, mean full-scale IQ increased with increasing Hg (change with 1SD of
      Hg=+2.02; 95%CI+1.40,+2.64 IQ points; P <0.0001); after adjustment effect size
      was reduced although still positive (+0.61;95%CI -0.06,+1.29 IQ points; P=0.073).
      The adjusted positive relationship was stronger when fish-eating mothers were
      considered separately (+0.84:95%CI +0.13,+1.56 IQ points; P=0.021) in comparison
      with the outcomes for non-fish eaters, where the adjusted relationship was
      negative (-2.22;95%CI -5.00,+0.56 IQ points; P=0.117). The binary outcome showed
      a similar pattern with the adjusted OR for non-fish-eaters 1.79 (95%CI 1.10,2.93;
      P=0.019) per SD of Hg, significantly different from that for fish consumers
      (0.94;95%CI:0.82,1.08)(Pinteraction<0.05). There were no differences between the
      sexes in the associations, nor did the level of the mother's blood selenium
      change the effect sizes. CONCLUSION: The relationship between intrauterine
      exposure to mercury and offspring IQ appears to be benign provided the mother
      consumes fish.

PMID- 28754501
TI  - Flexor carpi radialis brevis muscle: A case report and its prevalence in patients
      with carpal tunnel syndrome.
AB  - BACKGROUND: During the surgery for a distal radius fracture, we encountered a
      large anomalous muscle lying across the distal radius. The muscle was identified
      as a flexor carpi radialis brevis muscle (FCRB), based on its location, function,
      and innervation. This experience led us to clarify its prevalence in living
      subjects and alert surgeons of its presence. METHODS: We reviewed wrist MRI scans
      of 515 hands of 379 patients with carpal tunnel syndrome (CTS). The prevalence of
      the FCRB was calculated. The cross sectional area (CSA) of the FCRB was compared
      with that of the hypothenar muscles. Signal intensity and fat infiltration of the
      FCRB were assessed using semiquantitative methods. The anterior compartment ratio
      (CSA of the anterior compartment of the forearm was divided by CSA of the
      forearm. CSA of the FCRB was excluded for measurement) was compared between
      patients with and without FCRB. RESULTS: We found seven hands of six patients
      (1.6%) with a FCRB. All of these tendons were inserted into the second metacarpal
      base. CSA of FCRB was smaller than that of the hypothenar muscles.
      Semiquantitative assessment revealed normal signal intensities of the FCRB
      compared with those of other muscles. The anterior compartment ratio was smaller
      in patients with FCRB than without FCRB. None of the FCRB in our series
      demonstrated any sign of tendinitis on MRI. Furthermore, the postoperative
      clinical course for those patients was uneventful. CONCLUSIONS: Prevalence of
      FCRB in patients with CTS was 1.6%. FCRB should function as a wrist flexor. Its
      strength varied according to the individuals but was not greater than that of the
      hypothenar muscles. It is still unclear if the FCRB could cause the development
      of CTS. However, it was found that the FCRB could be a mass which occupies and
      narrows the anterior compartment.

PMID- 28754502
TI  - The impact of musculoskeletal diseases on mortality-comparison with internal
      diseases: A 15-year longitudinal study.
AB  - BACKGROUND: Aging is associated with an increased incidence of diabetes (DM),
      hypertension (HT), hyperlipidemia (HL), as well as musculoskeletal disorders,
      such as osteoarthritis (OA) and osteoporosis (OP). However, the impact of
      musculoskeletal disorders on mortality remains unclear. This study investigated
      the risk of mortality if having knee OA or OP. METHODS: 601 participants (mean
      age 67.8 +/- 5.3 years) who underwent musculoskeletal check-ups in Yakumo town
      were enrolled in this study, 248 were males and 353 were females. The following
      parameters were assessed: age, sex, body mass index, smoking habit, alcohol
      drinking habit, physical exercise habit, knee OA, OP, HT, DM and HL. Kaplan-Meier
      survival curves for smoking, drinking and physical exercise habits, knee OA, OP,
      HT, DM and HL were prepared, and the log-rank test was performed. Furthermore,
      the Cox hazard model was used for multivariate analysis of all variables.
      RESULTS: Knee OA, OP, HT, and DM were associated with a significantly higher
      mortality rate. Cox regression analysis results showed a hazard ratio of 1.972
      for OA (95%CI: 1.356-2.867), 1.965 for DM (1.146-3.368), 1.706 for smoking habits
      (1.141-2.552), and 1.614 for OP (1.126-2.313). Cardiovascular diseases were the
      most common causes of death. CONCLUSIONS: Smoking, knee OA, OP and DM were all
      associated with increased risk of mortality. Knee OA had a high hazard ratio,
      comparable to that of DM. These findings suggest that interventions against
      smoking, knee OA, OP and DM may reduce the risk of mortality.

PMID- 28754503
TI  - Risk stratification of coronary artery disease using radionuclides. Current
      status of clinical practice.
AB  - A discussion is presented on the current use of radioisotopes for evaluation of
      coronary artery disease in relation to other available techniques. The review is
      focused on coronary artery disease risk stratification employing single photon
      emission computed tomography and positron emission tomography, as well as on
      ischaemic cardiomyopathy and myocardial viability applications. Concepts are
      presented regarding coronary blood flow reserve, diagnostic and prognostic
      values, criteria for its appropriate use, as well as current methods to reduce
      unnecessary patient irradiation, in order to optimise nuclear cardiology
      practice.

PMID- 28754504
TI  - Provider Communication and Mothers' Willingness to Vaccinate Against Human
      Papillomavirus and Influenza: A Randomized Health Messaging Trial.
AB  - OBJECTIVE: To understand the effect of a health messaging intervention focused on
      provider communication about vaccination on mothers' willingness to vaccinate
      children against human papillomavirus (HPV) and seasonal influenza. METHODS: A
      total of 2476 mothers of 9- to 13-year-olds in the United States completed a Web
      based survey in August 2014. Mothers were randomized to 1 of 2 groups targeting
      HPV or influenza vaccine. Mothers whose child had not received the target vaccine
      (ie, zero doses of HPV vaccine/no prior-year administration of influenza vaccine)
      were randomized to the intervention. The study used a 3 * 2 between-subjects
      design; illustrated vignettes depicted 1 of 3 levels of provider recommendation
      strength (brief mention of vaccination, strong recommendation of vaccination, or
      personal disclosure of vaccination of own children), and presence or absence of
      information comparing safety of vaccination to the safety of a common daily
      activity. Outcome was mothers' willingness to have their child receive the target
      vaccine. Perceived benefits of vaccination were assessed before viewing the
      intervention and were included as a covariate in analyses, along with child
      gender. RESULTS: For HPV vaccine, there was a main effect of safety information
      (F(1,684) = 7.99, P = .005) and perceived benefits of vaccination (F(1,684) =
      221.64, P < .001) on mothers' willingness to vaccinate. For influenza, perceived
      benefits of vaccination significantly related to willingness to vaccinate
      (F(1,462) = 105.78, P < .001). Child gender was not associated with willingness.
      CONCLUSIONS: Provider communication about vaccination may need to be tailored to
      the vaccine in question. A next step to increasing coverage for both HPV and
      influenza vaccines may be an intervention aimed at increasing mothers' perceived
      benefits of vaccination.

PMID- 28754505
TI  - Mapping emotional disorders at the finest level: Convergent validity and joint
      structure based on alternative measures.
AB  - BACKGROUND: Traditional categorization of emotional disorders suffers from within
      disorder heterogeneity and excessive comorbidity. Quantitative nosology instead
      proposes grouping homogenous components of these disorders within a higher order
      internalizing dimension. However, the precise number, composition, and
      hierarchical structure of these components remains unclear and varies based on
      assessment tools. METHODS: The present study jointly examined two assessment
      systems with the broadest coverage of homogeneous emotional disorder components
      the revised Interview for Mood and Anxiety Symptoms (IMAS-R) and the self-report
      based expanded version of the Inventory of Depression and Anxiety Symptoms (IDAS
      II)-to map their convergent and discriminant validity and joint structure in
      outpatient (N=426) and treated student (N=306) samples. RESULTS: Results
      identified 33 non-redundant components of emotional disorders. Most demonstrated
      strong convergent and discriminant validity between these two instruments.
      However, the IMAS-R provided more detailed and differentiated characterization of
      the content subsumed within three IDAS-II scales, and seven of the 33 components
      were unique to one measure or the other. Joint analysis of scales from both
      measures supported a four factor (i.e., distress, fear, OCD, mania) mid-level
      structure of emotional disorders. CONCLUSIONS: Using multiple measures, methods,
      and samples, the present study provided evidence for the validity of core lower
      order components of the internalizing dimension and suggested they cluster into
      as many as four distinct factors reflecting distress, fear, OCD, and mania.

PMID- 28754507
TI  - Do we need yet another way to classify atrial fibrillation?

PMID- 28754506
TI  - The differentiated networks related to essential tremor onset and its amplitude
      modulation after alcohol intake.
AB  - The dysregulation of endogenous rhythms within brain networks have been
      implicated in a broad range of motor and non-motor pathologies. Essential tremor
      (ET), classically the purview of a single aberrant pacemaker, has recently become
      associated with network-level dysfunction across multiple brain regions.
      Specifically, it has been suggested that motor cortex constitutes an important
      node in a tremor-generating network involving the cerebellum. Yet the mechanisms
      by which these regions relate to tremor remain a matter of considerable debate.
      We sought to discriminate the contributions of cerebral and cerebellar
      dysregulation by combining high-density electroencephalography with subject
      specific structural MRI. For that, we contrasted ET with voluntary (mimicked)
      tremor before and after ingestion of alcohol to regulate the tremorgenic
      networks. Our results demonstrate distinct loci of cortical tremor coherence,
      most pronounced over the sensorimotor cortices in healthy controls, but more
      frontal motor areas in ET-patients consistent with a heightened involvement of
      the supplementary motor area. We further demonstrate that the reduction in tremor
      amplitude associated with alcohol intake is reflected in altered cerebellar - but
      not cerebral - coupling with movement. Taken together, these findings implicate
      tremor emergence as principally associated with increases in activity within
      frontal motor regions, whereas modulation of the amplitude of established tremor
      relates to changes in cerebellar activity. These findings progress a mechanistic
      understanding of ET and implicate network-level vulnerabilities in the rhythmic
      nature of communication throughout the brain.

PMID- 28754508
TI  - What are the gaps in quality measurement for lung cancer surgery?

PMID- 28754509
TI  - [Geriatric assessment before transcatheter aortic valve implantation in elderly
      patients].

PMID- 28754510
TI  - Mesoporous silica nanoparticles as a promising skin delivery system for
      methotrexate.
AB  - The systemic administration of methotrexate (MTX), a commonly used,
      antineoplastic drug which is also used in cutaneous disorders, is primarily
      associated with prolonged retention in the body and consequently with side
      effects. Innovative drug delivery techniques and alternative administration
      routes would therefore contribute to its safe and effective use. The general
      objective of this study is thus the development of MTX-based preparations for the
      topical treatment of skin disorders. MCM-41-like nanoparticles (MSN), are herein
      proposed as carriers which can improve the cutaneous absorption and hence the
      bioavailability and efficacy of MTX. The MTX/MSN complex, prepared via the
      impregnation procedure, has been physico-chemically characterized, while its cell
      cultures have had their biocompatibility and bioactivity tested. Furthermore, a
      series of stable MTX-based dermal formulations has been developed, some
      containing shea butter, a natural fat. Ex-vivo porcine skin absorption and the
      transepidermal permeation of MTX have also been monitored in a variety of media
      using Franz diffusion cells. Interestingly, the epidermal accumulation of the
      active molecule was increased by its inclusion into MSN, regardless of the
      surrounding medium. Furthermore, the presence of shea butter enhanced the skin
      uptake of the drug both in the free and in the loaded form.

PMID- 28754511
TI  - Towards understanding polyol additive effects on the pH shift-induced aggregation
      of a monoclonal antibody using high throughput screening and quantitative
      structure-activity modeling.
AB  - pH shift-induced aggregation is frequently observed in downstream processing of
      monoclonal antibodies and has been shown to depend on solvent composition. To
      quantify the stabilizing effect of polyol additives against aggregation, we
      determined aggregation rate constants in the presence of a set of 14 compounds.
      Rate constants were then correlated with molecular descriptors in a quantitative
      structure activity relationship (QSAR) approach. The molecular size, volume, the
      charge, number of hydrogen acceptors, the stereochemistry and hydrophobicity of
      the compounds were identified as important descriptors. Generally larger
      compounds with a balanced surface polarity tend to inhibit aggregation better
      while hydrophobicity plays an important role at the nucleation phase, with
      hydrophobic compounds being more potent at inhibiting aggregation.

PMID- 28754512
TI  - Sustained-release mitochondrial protonophore reverses nonalcoholic fatty liver
      disease in rats.
AB  - As a mitochondrial uncoupler, 2,4-dinitrophenol (DNP) is proven therapeutically
      effective against nonalcoholic fatty liver disease (NAFLD) by uncoupling
      oxidation and phosphorylation. However, a major factor that impedes the clinical
      application of DNP is the significant side effects derived from its frequent
      hyperthermia and even death. In this study, we developed an injectable liquid
      crystal gel (DNP-LC-gel) to reduce the toxicity of DNP. DNP-LC-gel achieved
      sustained release and maintained DNP plasma concentration at an effective drug
      level. In a rat model of NAFLD, DNP-LC-gel treated rats reduced hepatic
      steatosis, liver triglyceride content, plasma triacylglycerol (TG) and total
      cholesterol (TC) content. Compared with DNP solution (DNP-soln), rats after DNP
      LC-gel treatment showed no body temperature toxicity and local irritation. All
      results above indicated that DNP-LC-gel has a great potential for NAFLD therapy.

PMID- 28754513
TI  - [Acute disseminated encephalomyelitis associated with Crohn disease under
      infliximab].

PMID- 28754514
TI  - Comparative efficacy of chemical stabilizers on the thermostabilization of a
      novel live attenuated buffalopox vaccine.
AB  - In the present investigation, the thermostability of a live attenuated buffalopox
      vaccine prepared with an indigenous baffalopox virus isolate (BPXV Vij/96) and
      freeze-dried under conventional lyophilizing conditions is described. Three
      different stabilizer combinations like LS (lactalbumin hydralysate + sucrose),
      LHT (lactalbumin hydralysate + Trehalose dihydrate) and TAA (Trehalose dihydrate
      + l- Alanine + l-Histidine) were used to prepare the vaccine. The study indicated
      that the LS stabilizer was found to be the stabilizer of choice followed by LHT
      and TAA for buffalopox vaccine at all temperatures studied. The presence of
      stabilizers has beneficial influence in preserving the keeping quality of the
      vaccine. Further, among the diluents used to reconstitute the freeze-dried
      buffalopox vaccine, double distilled water, 0.85% normal saline solution and
      phosphate buffer saline were the choice of diluents in that order. However, 1M
      MgSO4 did not perform well at higher temperatures. Investigation suggests for
      using LS as a stabilizer for freeze-drying and any of the three diluents except
      1MgSO4 for reconstitution of buffalopox vaccine.

PMID- 28754516
TI  - Recall Tests Are Effective to Detect Mild Cognitive Impairment: A Systematic
      Review and Meta-analysis of 108 Diagnostic Studies.
AB  - BACKGROUND: Mild cognitive impairment (MCI) is a prevalent symptom associated
      with the increased risk of dementia. There are many cognitive tests available for
      detection of MCI, and investigation of the diagnostic performance of the tests is
      deemed necessary. OBJECTIVE: This study aims to evaluate the diagnostic
      performance of different cognitive tests used for MCI detection. DATA SOURCES: A
      list of cognitive tests was identified in previous reviews and from online search
      engines. Literature searches were performed on each of the cognitive tests in
      MEDLINE, Embase, and PsycINFO from the earliest available dates of individual
      databases to December 31, 2016. Google Scholar was used as a supplementary search
      tool. STUDY SELECTION: Studies that were used to assess the diagnostic
      performance of the cognitive tests were extracted with inclusion and exclusion
      criteria. Each test's performance was compared with the standard diagnostic
      criteria. Bivariate random effects models were used to summarize the test
      performance as a point estimate for sensitivity and specificity, and presented in
      a summary receiver operating characteristic curve. Reporting quality and risk of
      bias were evaluated. RESULTS: A total of 108 studies with 23,546 participants
      were selected to evaluate 9 cognitive tests for MCI detection. Most of the
      studies used the Mini-Mental State Examination (MMSE) (n = 58) and the Montreal
      Cognitive Assessment (MoCA) (n = 35). The combined diagnostic performance of the
      MMSE in MCI detection was 0.71 sensitivity [95% confidence interval (CI): 0.66
      0.75] and 0.74 specificity (95% CI: 0.70-0.78), and of the MoCA in MCI detection
      was 0.83 sensitivity (95% CI: 0.80-0.86) and 0.75 specificity (95% CI: 0.69
      0.80). Among the 9 cognitive tests, recall tests showed the best diagnostic
      performance with 0.89 sensitivity (95% CI: 0.86-0.92) and 0.84 specificity (95%
      CI, 0.79-0.89). In subgroup analyses, long- or short-delay recall tests have
      shown better performance than immediate recall tests. CONCLUSIONS: Recall tests
      were shown to be the most effective test in MCI detection, especially for the
      population with symptoms of memory deterioration. They can be potentially used as
      the triage screening test for MCI in primary care setting. But when a patient
      shows cognitive impairments beyond memory deterioration, a more comprehensive
      test such as the MoCA should be used.

PMID- 28754517
TI  - Does Person-Centered Care Improve Residents' Satisfaction With Nursing Home
      Quality?
AB  - OBJECTIVE: Person-centered care (PCC) is meant to enhance nursing home residents'
      quality of life (QOL). Including residents' perspectives is critical to
      determining whether PCC is meeting residents' needs and desires. This study
      examines whether PCC practices promote satisfaction with QOL and quality of care
      and services (QOC and QOS) among nursing home residents. DESIGN: A longitudinal,
      retrospective cohort study using an in-person survey. SETTING: Three hundred
      twenty nursing homes in Kansas enrolled or not enrolled in a pay-for-performance
      program, Promoting Excellent Alternatives in Kansas (PEAK 2.0), to promote PCC in
      nursing homes. PARTICIPANTS: A total of 6214 nursing home residents in 2013-2014
      and 5538 residents in 2014-2015, with a Brief Interview for Mental Status score
      >=8, participated in face-to-face interviews. Results were aggregated to the
      nursing home level. MEASUREMENTS: My InnerView developed a Resident Satisfaction
      Survey for Kansas composed of 32 questions divided into QOL, QOC, QOS, and global
      satisfaction subdomains. RESULTS: After controlling for facility characteristics,
      satisfaction with overall QOL and QOC was higher in homes that had fully
      implemented PCC. Although some individual measures in the QOS domain (eg, food)
      showed greater satisfaction at earlier levels of implementation, high
      satisfaction was observed primarily in homes that had fully implemented PCC.
      CONCLUSION: These findings provide evidence for the effectiveness of PCC
      implementation on nursing home resident satisfaction. The PEAK 2.0 program may
      provide replicable methods for nursing homes and states to implement PCC
      systematically.

PMID- 28754515
TI  - Maternal Systemic Interleukin-6 During Pregnancy Is Associated With Newborn
      Amygdala Phenotypes and Subsequent Behavior at 2 Years of Age.
AB  - BACKGROUND: Maternal inflammation during pregnancy increases the risk for
      offspring psychiatric disorders and other adverse long-term health outcomes. The
      influence of inflammation on the developing fetal brain is hypothesized as one
      potential mechanism but has not been examined in humans. METHODS: Participants
      were adult women (N = 86) who were recruited during early pregnancy and whose
      offspring were born after 34 weeks' gestation. A biological indicator of maternal
      inflammation (interleukin-6) that has been shown to influence fetal brain
      development in animal models was quantified serially in early, mid-, and late
      pregnancy. Structural and functional brain magnetic resonance imaging scans were
      acquired in neonates shortly after birth. Infants' amygdalae were individually
      segmented for measures of volume and as seeds for resting state functional
      connectivity. At 24 months of age, children completed a snack delay task to
      assess impulse control. RESULTS: Higher average maternal interleukin-6
      concentration during pregnancy was prospectively associated with larger right
      amygdala volume and stronger bilateral amygdala connectivity to brain regions
      involved in sensory processing and integration (fusiform, somatosensory cortex,
      and thalamus), salience detection (anterior insula), and learning and memory
      (caudate and parahippocampal gyrus). Larger newborn right amygdala volume and
      stronger left amygdala connectivity were in turn associated with lower impulse
      control at 24 months of age, and mediated the association between higher maternal
      interleukin-6 concentrations and lower impulse control. CONCLUSIONS: These
      findings provide new evidence in humans linking maternal inflammation during
      pregnancy with newborn brain and emerging behavioral phenotypes relevant for
      psychiatric disorders. A better understanding of intrauterine conditions that
      influence offspring disease susceptibility is warranted to inform targeted early
      intervention and prevention efforts.

PMID- 28754518
TI  - Myofibroblastic sarcoma of the trapezius muscle.

PMID- 28754519
TI  - Long-term analysis of Zostera noltei: A retrospective approach for understanding
      seagrasses' dynamics.
AB  - Long-term studies are necessary to establish trends and to understand seagrasses'
      spatial and temporal dynamic. Nevertheless, this type of research is scarce, as
      the required databases are often unavailable. The objectives of this study are to
      create a method for mapping the seagrass Zostera noltei using remote sensing
      techniques, and to apply it to the characterization of the meadows' extension
      trend and the potential drivers of change. A time series was created using a
      novel method based on remote sensing techniques that proved to be adequate for
      mapping the seagrass in the emerged intertidal. The meadows seem to have a
      decreasing trend between 1984 and the early 2000s, followed by an increasing
      tendency that represents a recovery in the extension area of the species. This 30
      year analysis demonstrated the Z. noltei's recovery in the study site, similar to
      that in other estuaries nearby and contrary to the worldwide decreasing behavior
      of seagrasses.

PMID- 28754520
TI  - Mercury concentration trend as a possible result of changes in cod population
      demography.
AB  - Mercury (Hg) in Atlantic cod (Gadus morhua) is one of many parameters that are
      monitored through OSPAR's Joint Assessment and Monitoring Programme. Time series
      for cod in the Inner Oslofjord (Norway) go back to 1984. Until 2014, annual
      median Hg-concentrations in cod from the Inner Oslofjord showed both significant
      upward long-term (whole time series) and short-term (recent 10 years) trends
      (when 2015 was included, the short-term trend was not significant). However, the
      median length of the cod sampled also showed upward trends. This may have been
      caused by low cod recruitment in the area since the start of the 2000s, as
      indicated by beach seine surveys. To investigate how length would impact the
      trend analysis, the Hg-concentrations in the cod were normalised to 50 cm. No
      significant short-term trend in Hg-concentrations could be detected for length
      normalised concentrations. The results indicated that most of the upward trend in
      Hg-concentrations could be attributed to the sampling of larger fish. The reasons
      for the apparent change in the cod population demography are not conclusive,
      however, sampling bias must also be considered.

PMID- 28754521
TI  - The role of fatty acids and triglycerides in the gonads of Paracentrotus lividus
      from Sardinia: Growth, reproduction and cold acclimatization.
AB  - A detailed characterization of lipid extracts from gonads of P. lividus over a
      year has been performed combining GC and NMR measurements. For this purpose, sea
      urchins from two different Sardinian coastal areas were collected monthly. The
      results underlined a correlation between gonad fatty acids profiles and both
      water temperature and reproduction process. In particular, EPA and ARA appear to
      be the most altered fatty acids following seasonal changes. It is suggested that
      EPA could represent a biomarker of reproduction, reaching a content around 14%
      during gametogenesis, mainly due to an increase of the sn-1,3 position in TAGs.
      On the contrary, ARA seems to play a more important role in response to cold
      acclimatization, which is reflected in a modulation of ARA content in the sn-1,3
      position in TAGs.

PMID- 28754522
TI  - Finding patients using similarity measures in a rare diseases-oriented clinical
      data warehouse: Dr. Warehouse and the needle in the needle stack.
AB  - OBJECTIVE: In the context of rare diseases, it may be helpful to detect patients
      with similar medical histories, diagnoses and outcomes from a large number of
      cases with automated methods. To reduce the time to find new cases, we developed
      a method to find similar patients given an index case leveraging data from the
      electronic health records. MATERIALS AND METHODS: We used the clinical data
      warehouse of a children academic hospital in Paris, France (Necker-Enfants
      Malades), containing about 400,000 patients. Our model was based on a vector
      space model (VSM) to compute the similarity distance between an index patient and
      all the patients of the data warehouse. The dimensions of the VSM were built upon
      Unified Medical Language System concepts extracted from clinical narratives
      stored in the clinical data warehouse. The VSM was enhanced using three
      parameters: a pertinence score (TF-IDF of the concepts), the polarity of the
      concept (negated/not negated) and the minimum number of concepts in common. We
      evaluated this model by displaying the most similar patients for five different
      rare diseases: Lowe Syndrome (LOWE), Dystrophic Epidermolysis Bullosa (DEB),
      Activated PI3K delta Syndrome (APDS), Rett Syndrome (RETT) and Dowling Meara (EBS
      DM), from the clinical data warehouse representing 18, 103, 21, 84 and 7 patients
      respectively. RESULTS: The percentages of index patients returning at least one
      true positive similar patient in the Top30 similar patients were 94% for LOWE,
      97% for DEB, 86% for APDS, 71% for EBS-DM and 99% for RETT. The mean number of
      patients with the exact same genetic diseases among the 30 returned patients was
      51%. CONCLUSION: This tool offers new perspectives in a translational context to
      identify patients for genetic research. Moreover, when new molecular bases are
      discovered, our strategy will help to identify additional eligible patients for
      genetic screening.

PMID- 28754523
TI  - Development and classification of a robust inventory of near real-time outcome
      measurements for assessing information technology interventions in health care.
AB  - OBJECTIVE: To develop and classify an inventory of near real-time outcome
      measures for assessing information technology (IT) interventions in health care
      and assess their relevance as perceived by experts in the field. MATERIALS AND
      METHODS: To verify the robustness and coverage of a previously published
      inventory of measures and taxonomy, we conducted semi-structured interviews with
      clinical and administrative leaders from a large care delivery system to collect
      suggestions of outcome measures that can be calculated with data available in
      electronic format for near real-time monitoring of EHR implementations. We
      combined these measures with the most commonly reported in the literature. We
      then conducted two online surveys with subject-matter experts to collect their
      perceptions of the relevance of the measures, and identify other potentially
      relevant measures. RESULTS: With input from experienced health care leaders and
      informaticists, we developed an inventory of 102 outcome measures. These measures
      were classified into a taxonomy of commonly used measures around the categories
      of quality, productivity, and safety. Safety measures were rated as most relevant
      by subject-matter experts, especially those measuring medication processes.
      Clinician satisfaction and measures assessing mean time to complete tasks and
      time spent on electronic documentation were also rated as highly relevant.
      DISCUSSION: By expanding the coverage of our previously published inventory and
      taxonomy, we expect to help providers, health IT vendors and researchers to more
      effectively and consistently monitor the impact of EHR implementations in near
      real-time, and report more standardized outcomes in future studies. We identified
      several measures not commonly assessed by previous studies of IT implementations,
      especially those of safety and productivity, which deserve more attention from
      the broader informatics community. CONCLUSION: Our inventory of measures and
      taxonomy will help researchers identify gaps in their measurement approaches and
      report more standardized measurements of IT interventions that could be shared
      among researchers, hopefully facilitating comparison across future studies and
      increasing our understanding of the impact of IT interventions in health care.

PMID- 28754524
TI  - Reply to Letter: Was capnographic waveform the gold standard to confirm the
      endotracheal intubation? We need more proof.

PMID- 28754525
TI  - Reply to letter: Neurocognitive and behavioral outcomes in a nearly drowned child
      with cardiac arrest and hypothermia resuscitated after 43min of no flow-time: A
      case study.

PMID- 28754526
TI  - Telephone cardiopulmonary resuscitation is independently associated with improved
      survival and improved functional outcome after out-of-hospital cardiac arrest.
AB  - AIM OF STUDY: This study aims to quantify the relative impact of Dispatcher
      Initiated Telephone cardiopulmonary resuscitation (TCPR) on survival and survival
      with favorable functional outcome after out-of-hospital cardiac arrest (OHCA) in
      a population of patients served by multiple emergency dispatch centers and more
      than 130 emergency medical services (EMS) agencies. METHODS: We conducted a
      retrospective, observational study of EMS-treated adult (>=18 years) patients
      with OHCA of presumed cardiac origin in Arizona, between January 1, 2011, and
      December 31, 2014. We compared survival and functional outcome among three
      distinct groups of OHCA patients: those who received no CPR before EMS arrival
      (no CPR group); those who received BCPR before EMS arrival and prior to or
      without telephone CPR instructions (BCPR group); and those who received TCPR
      (TCPR group). RESULTS: In this study, 2310 of 4391 patients met the study
      criteria (median age, 62 years; IQR 50, 74; 1540 male). 32.8% received no CPR,
      23.8% received Bystander-Initiated CPR and 43.4% received TCPR. Overall survival
      was 11.5%. Using no CPR as the reference group, the multivariate adjusted odds
      ratio for survival at hospital discharge was 1.51 (95% confidence interval [CI],
      1.04, 2.18) for BCPR and 1.64 (95% CI, 1.16, 2.30) for TCPR. The multivariate
      adjusted odds ratio of favorable functional outcome at discharge was 1.58 (95% CI
      1.05, 2.39) for BCPR and 1.56 (95% CI, 1.06, 2.31) for TCPR. CONCLUSION: TCPR is
      independently associated with improved survival and improved functional outcome
      after OHCA.

PMID- 28754527
TI  - Ultrasound use during cardiopulmonary resuscitation is associated with delays in
      chest compressions.
AB  - AIM: High-quality chest compressions are a critical component of the
      resuscitation of patients in cardiopulmonary arrest. Point-of-care ultrasound
      (POCUS) is used frequently during emergency department (ED) resuscitations, but
      there has been limited research assessing its benefits and harms during the
      delivery of cardiopulmonary resuscitation (CPR). We hypothesized that use of
      POCUS during cardiac arrest resuscitation adversely affects high-quality CPR by
      lengthening the duration of pulse checks beyond the current cardiopulmonary
      resuscitation guidelines recommendation of 10s. METHODS: We conducted a
      prospective cohort study of adults in cardiac arrest treated in an urban ED
      between August 2015 and September 2016. Resuscitations were recorded using video
      equipment in designated resuscitation rooms, and the use of POCUS was documented
      and timed. A linear mixed-effects model was used to estimate the effect of POCUS
      on pulse check duration. RESULTS: Twenty-three patients were enrolled in our
      study. The mean duration of pulse checks with POCUS was 21.0s (95% CI, 18-24)
      compared with 13.0s (95% CI, 12-15) for those without POCUS. POCUS increased the
      duration of pulse checks and CPR interruption by 8.4s (95% CI, 6.7-10.0
      [p<0.0001]). Age, body mass index (BMI), and procedures did not significantly
      affect the duration of pulse checks. CONCLUSIONS: The use of POCUS during cardiac
      arrest resuscitation was associated with significantly increased duration of
      pulse checks, nearly doubling the 10-s maximum duration recommended in current
      guidelines. It is important for acute care providers to pay close attention to
      the duration of interruptions in the delivery of chest compressions when using
      POCUS during cardiac arrest resuscitation.

PMID- 28754528
TI  - Corrigendum to "Isolated Systolic Hypertension: An Update after SPRINT" American
      Journal of Medicine Volume 129, Issue 12, December 2016, Pages 1251-1258.

PMID- 28754529
TI  - Lung transplant outpatient clinic at Centro Hospitalar Sao Joao - 10 year review.

PMID- 28754530
TI  - Tuberculosis in children from diagnosis to decision to treat.
AB  - SETTING: Confirmation of tuberculosis (TB) in children is difficult, so
      clinicians use different procedures when deciding to treat. OBJECTIVE: Identify
      criteria to initiate and maintain TB treatment in children younger than 5 years
      old, without diagnosis confirmation. DESIGN: A web-based survey was distributed
      by email to the corresponding authors of journal articles on childhood TB. The
      observations were clustered into disjoint groups, and analyzed by Ward's method.
      RESULTS: We sent out 260 questionnaires and received 64 (24.6%) responses. Forty
      six respondents (71.9%) said that microbiological confirmation was not important
      for initiation of anti-TB treatment, and that the epidemiological context and
      signs/symptoms suggestive of disease were most important. Sixty-one respondents
      (95.3%) said that the decision to continue therapy was mainly dependent on
      clinical improvement. A cluster of older respondents (median age: 52 years-old)
      who were active at a hospital or primary health care centre placed the most value
      on immunological test results and chest X-rays. A cluster of younger respondents
      (median age: 38 years-old) who were less experienced in management of TB placed
      more value on Interferon Gamma Release Assay (IGRA) results and chest computed
      tomography (CT) scans. A cluster of respondents with more experience in treating
      TB and working at specialized TB centres placed greater value on the clinical
      results and specific radiological alterations ("tree-in-bud" pattern and pleural
      effusion). CONCLUSION: TB management varied according to the age, work location
      and experience of the clinicians. It is necessary to establish standardized
      guidelines used for the diagnosis and decision to treat TB in children.

PMID- 28754531
TI  - CARF is a multi-module regulator of cell proliferation and a molecular bridge
      between cellular senescence and carcinogenesis.
AB  - CARF (Collaborator of ARF) was first identified as an ARF (Alternative Reading
      Frame, p14ARF)-interacting protein in a yeast two-hybrid interactive screening.
      Subsequently, it was shown to stabilize the p53-tumor suppressor protein in an
      ARF-dependent or -independent manner. It acts as a transcriptional repressor of
      HDM2 that exerts a negative feedback on p53 by its proteasomal-mediated
      degradation. CARF-driven control over p53-HDM2-p21WAF1 axis was shown to regulate
      cell proliferative fates. Cells with CARF-overexpression (CARF-OE) and
      superexpression (CARF-SE) showed growth arrest and pro-proliferative phenotypes,
      respectively. On the other hand, apoptosis was triggered in CARF-compromised
      cells. In the present review, we provide a comprehensive current understanding
      into the molecular mechanisms of CARF functions in regulation of DNA damage
      response, cell cycle checkpoints, cell survival and death signaling pathways. We
      discuss how thresh-hold of CARF level determines fate of cells to senescence and
      malignant transformation.

PMID- 28754532
TI  - Centenarians maintain miRNA biogenesis pathway while it is impaired in
      octogenarians.
AB  - Centenarians but not octogenarians up regulate the expression of miRNAs, as we
      previously reported. We have looked into miRNA biogenesis. We show that RNA POL
      II, DROSHA, EXPORTIN 5 and DICER, are up-regulated in centenarians compared with
      octogenarians. Furthermore, factors involved in the control of these miRNAs
      biogenesis genes are also up-regulated in centenarians. Therefore, the up
      regulation of miRNA expression in centenarians can be explained in part because
      miRNA biogenesis pathway is depressed in octogenarians (ordinary aging) while it
      is maintained in centenarians (extraordinary aging).

PMID- 28754533
TI  - Benefits and Harms of Treatment of Asymptomatic Bacteriuria: A Systematic Review
      and Meta-analysis by the European Association of Urology Urological Infection
      Guidelines Panel.
AB  - : People with asymptomatic bacteriuria (ABU) are often unnecessarily treated with
      antibiotics risking adverse effects and antimicrobial resistance. We performed a
      systematic review to determine any benefits and harms of treating ABU in
      particular patient groups. Relevant databases were searched and eligible trials
      were assessed for risk-of-bias and Grading of Recommendations, Assessment,
      Development and Education quality. Where possible, a meta-analysis of extracted
      data was performed or a narrative synthesis of the evidence was presented. After
      screening 3626 articles, 50 studies involving 7088 patients were included.
      Overall, quality of evidence ranged from very low to low. There was no evidence
      of benefit for patients with no risk factors, patients with diabetes mellitus,
      postmenopausal women, elderly institutionalised patients, patients with renal
      transplants, or patients prior to joint replacement, and treatment was harmful
      for patients with recurrent urinary tract infection (UTI). Treatment of ABU
      resulted in a lower risk of postoperative UTI after transurethral resection
      surgery. In pregnant women, we found evidence that treatment of ABU decreased
      risk of symptomatic UTI, low birthweight, and preterm delivery. ABU should be
      treated prior to transurethral resection surgery. In addition, current evidence
      also suggests that ABU treatment is required in pregnant women, although the
      results of a recent trial have challenged this view. PATIENT SUMMARY: We reviewed
      available scientific studies to see if people with bacteria in their urine but
      without symptoms of urinary tract infection should be treated with antibiotics to
      eliminate bacteria. For most people, treatment was not beneficial and may be
      harmful. Antibiotic treatment did appear to benefit women in pregnancy and those
      about to undergo urological surgery.

PMID- 28754534
TI  - Health-related quality of life during trans-arterial chemoembolization with drug
      eluting beads loaded with doxorubicin (DEBDOX) for unresectable hepatic
      metastases from ocular melanoma.
AB  - BACKGROUND: We have previously reported favorable response and survival rates
      using drug-eluting beads loaded with doxorubicin (DEBDOX) for unresectable
      hepatic metastases. This study investigates the quality of life (QoL) impact of
      DEBDOX for the treatment of unresectable hepatic metastases from melanoma.
      METHODS: A multi-center, prospective, non-controlled clinical trial was reviewed.
      QoL was assessed at baseline and after each treatment, and doxorubicin-specific
      effects were assessed after each treatment. RESULTS: Twenty patients received 61
      DEBDOX treatments. After each treatment, at least 83% of patients reported
      "little" to "none" doxorubicin-related symptoms. For the 8 FACT-Hep subscales,
      QoL scores were unchanged through 3 treatments for 18 of 24 total time points by
      ANOVA, with a small-to-moderate ES change through the last treatment in 36 of 40
      time points. CONCLUSIONS: Hepatic arterial therapy with DEBDOX is safe with
      minimal QOL changes in treating unresectable liver-dominant melanoma metastasis.
      CLINICAL TRIAL: NCT01010984.

PMID- 28754535
TI  - Stapled Transabdominal Ostomy Reinforcement with retromuscular mesh (STORRM):
      Technical details and early outcomes of a novel approach for retromuscular repair
      of parastomal hernias.
AB  - BACKGROUND: Parastomal hernia repair (PHR) remains a challenge with no optimal
      repair technique. During retromuscular hernia repair, traversing the stomal
      conduit through the abdominal wall can result in angulation and compression.
      Widening of traditional cruciate incisions in mesh and/or fascia likely
      contributes to recurrences. To address these pitfalls, the Stapled Transabdominal
      Ostomy Reinforcement with Retromuscular Mesh (STORRM) technique utilizing a
      circular stapler was developed. METHODS: A prospective registry of consecutive
      patients undergoing STORRM was analyzed. We characterized demographics, hernia
      characteristics, and perioperative results. Primary outcomes were complications,
      surgical site events (SSEs) and hernia recurrence. RESULTS: 12 patients underwent
      PHR with STORRM; mean age 64 and BMI 36 kg/m2. Synthetic mesh was used in 92% of
      patients. We observed two (17%) SSEs, one case of cellulitis and one organ space
      infection. With mean 12.8-month follow-up, we documented two recurrences.
      CONCLUSIONS: STORRM represents a safe method to repair parastomal hernias. The
      unified aperture with stapled reinforcement results in reproducible repairs,
      minimizing intestinal angulation associated with traditional stoma passage. Early
      outcomes evidenced minimal complications and favorable recurrence rate.

PMID- 28754536
TI  - The impact of positive and negative intraoperative surgeons' leadership behaviors
      on surgical team performance.
AB  - BACKGROUND: The effects of surgeons' leadership on team performance are not well
      understood. The purpose of this study was to examine the simultaneous effects of
      transformational, passive, abusive supervision and over-controlling leadership
      behaviors by surgeons on surgical team performance. METHODS: Trained observers
      attended 150 randomly selected operations at a tertiary care teaching hospital.
      Observers recorded instances of the four leadership behaviors enacted by the
      surgeon. Postoperatively, team members completed validated questionnaires rating
      team cohesion and collective efficacy. Multiple regression analyses were
      computed. Data were analyzed using the complex modeling function in MPlus.
      RESULTS: Surgeons' abusive supervision was negatively associated with
      psychological safety (unstandardized B = -0.352, p < 0.01). Both surgeons'
      abusive supervision (unstandardized B = -0.237, p < 0.01), and over-controlling
      leadership (unstandardized B = -0.230, p < 0.05) were negatively associated with
      collective efficacy. CONCLUSIONS: This study is the first to assess the
      simultaneous effects of surgeons' positive and negative leadership behaviors on
      intraoperative team performance. Significant effects only surfaced for negative
      leadership behaviors; transformational leadership did not positively influence
      team performance.

PMID- 28754537
TI  - Functional analysis of human aromatic amino acid transporter MCT10/TAT1 using the
      yeast Saccharomyces cerevisiae.
AB  - Tryptophan is an essential amino acid in humans and an important serotonin and
      melatonin precursor. Monocarboxylate transporter MCT10 is a member of the SLC16A
      family proteins that mediates low-affinity tryptophan transport across
      basolateral membranes of kidney, small intestine, and liver epithelial cells,
      although the precise transport mechanism remains unclear. Here we developed a
      simple functional assay to analyze tryptophan transport by human MCT10 using a
      deletion mutant for the high-affinity tryptophan permease Tat2 in Saccharomyces
      cerevisiae. tat2Deltatrp1 cells are defective in growth in YPD medium because
      tyrosine present in the medium competes for the low-affinity tryptophan permease
      Tat1 with tryptophan. MCT10 appeared to allow growth of tat2Deltatrp1 cells in
      YPD medium, and accumulate in cells deficient for Rsp5 ubiquitin ligase. These
      results suggest that MCT10 is functional in yeast, and is subject to ubiquitin
      dependent quality control. Whereas growth of Tat2-expressing cells was
      significantly impaired by neutral pH, that of MCT10-expressing cells was nearly
      unaffected. This property is consistent with the transport mechanism of MCT10 via
      facilitated diffusion without a need for pH gradient across the plasma membrane.
      Single-nucleotide polymorphisms (SNPs) are known to occur in the human MCT10
      coding region. Among eight SNP amino acid changes in MCT10, the N81K mutation
      completely abrogated tryptophan import without any abnormalities in the
      expression or localization. In the MCT10 modeled structure, N81 appeared to
      protrude into the putative trajectory of tryptophan. Plasma membrane localization
      of MCT10 and the variant proteins was also verified in human embryonic kidney
      293T cells.

PMID- 28754539
TI  - In vitro genotoxicity and cytotoxicity of polydopamine-coated magnetic
      nanostructures.
AB  - Synthesis of magnetic nanoparticles and magnetic nanoclusters was performed by
      the co-precipitation method or solvothermal synthesis, respectively, followed by
      oxidative polymerization of dopamine, resulting in a polydopamine (PDA) shell.
      The nanomaterials obtained were described using TEM, FTIR and magnetic
      measurements. For the first time, cyto- and genotoxicity studies of polydopamine
      coated nanostructures were performed on cancer and normal cell lines, providing
      in-depth insight into the toxicity of such materials. The tests conducted, e.g.
      ROS, apoptosis and DNA double-break of the nanomaterials obtained revealed the
      low toxicity of these structures. Thus, these results prove the biocompatibility
      and low genotoxicity of these materials and provide new data on the toxicity of
      PDA-coated materials, which is of great importance for their biomedical
      application.

PMID- 28754538
TI  - Dynamic roles for the N-terminus of the yeast G protein-coupled receptor Ste2p.
AB  - The Saccharomyces cerevisiae alpha-factor receptor Ste2p has been used
      extensively as a model to understand the molecular mechanism of signal
      transduction by G protein-coupled receptors (GPCRs). Single and double cysteine
      mutants of Ste2p were created and served as surrogates to detect intramolecular
      interactions and dimerization of Ste2p using disulfide cross-linking methodology.
      When a mutation was introduced into the phylogenetically conserved tyrosine
      residue at position 26 (Y26C) in the N-terminus of Ste2p, dimerization was
      increased greatly. The amount of dimer formed by this Y26C mutant was greatly
      reduced by ligand binding even though the ligand binding site is far removed from
      the N-terminus; the lowering of the dimer formation was consistent with a
      conformational change in the N-terminus of the receptor upon activation.
      Dimerization was decreased by double mutations Y26C/V109C or Y26C/T114C
      indicating that Y26 is in close proximity to V109 and T114 of extracellular loop
      1 in native Ste2p. Combined with earlier studies, these results indicate
      previously unrecognized roles for the N-terminus of Ste2p, and perhaps of GPCRs
      in general, and reveal a specific N-terminus residue or region, that is involved
      in GPCR signaling, intrareceptor interactions, and receptor dimerization.

PMID- 28754540
TI  - Decision Support with the Personal Patient Profile-Prostate: A Multicenter
      Randomized Trial.
AB  - PURPOSE: We evaluated the efficacy of the web based P3P (Personal Patient Profile
      Prostate) decision aid vs usual care with regard to decisional conflict in men
      with localized prostate cancer. MATERIALS AND METHODS: A randomized (1:1),
      controlled, parallel group, nonblinded trial was performed in 4 regions of the
      United States. Eligible men had clinically localized prostate cancer and an
      upcoming consultation, and they spoke and read English or Spanish. Participants
      answered questionnaires to report decision making stage, personal
      characteristics, concerns and preferences plus baseline symptoms and decisional
      conflict. A randomization algorithm allocated participants to receive tailored
      education and communication coaching, generic teaching sheets and external
      websites plus a 1-page summary to clinicians (intervention) or the links plus
      materials provided in clinic (usual care). Conflict outcomes and the number of
      consultations were measured at 1 month. Univariate and multivariable models were
      used to analyze outcomes. RESULTS: A total of 392 men were randomized, including
      198 to intervention and 194 to usual care, of whom 152 and 153, respectively,
      returned 1-month outcomes. The mean +/- SD 1-month decisional conflict scale
      (score range 0 to 100) was 10.9 +/- 16.7 for intervention and 9.9 +/- 18.0 for
      usual care. The multivariable model revealed significantly reduced conflict in
      the intervention group (-5.00, 95% CI -9.40--0.59). Other predictors of conflict
      included income, marital or partner status, decision status, number of
      consultations, clinical site and D'Amico risk classification. CONCLUSIONS: In
      this multicenter trial the decision aid significantly reduced decisional
      conflict. Other variables impacted conflict and modified the effect of the
      decision aid, notably risk classification, consultations and resources. P3P is an
      effective adjunct for shared decision making in men with localized prostate
      cancer.

PMID- 28754541
TI  - Benzophenone glycosides from the flower buds of Aquilaria sinensis.
AB  - Four new benzophenone glycosides named as aquilaside A-D (1-4) along with five
      known compounds (5-9) were isolated from the methanol extract of the flower buds
      of Aquilaria sinensis. Their structures were elucidated on the basis of 1D and 2D
      NMR and mass spectroscopic analyses. All purified compounds were evaluated for
      their anti-inflammatory and cytotoxic activities. Aquilasides B and C displayed
      moderate cytotoxicity against SK-MEL cells with IC50 of 17.0 and 12.0MUM and weak
      NF-kappaB inhibitive activity at 100MUM with 30% and 60%, respectively.

PMID- 28754542
TI  - Evaluation of liver fibrosis using Raman spectroscopy and infrared thermography:
      A pilot study.
AB  - Liver fibrosis is a pathological process that can escalate to cirrhosis and then
      liver failure, a major public health concern that affect hundreds of millions of
      people in both developed and developing countries. Detection of liver fibrosis
      during its earlier stages is a matter of great importance which may allow
      prevention of development of cirrhosis in patients with chronic liver disease. In
      this work, Raman spectroscopy and thermography were evaluated to detect early
      pathological signs of liver fibrosis in rats in which liver fibrosis was induced
      using carbon tetrachloride. Results show that Raman spectra of healthy and
      fibrotic livers significantly differ among each other and can be classified by
      principal component analysis and discriminant analysis. The PCA-LDA method has a
      sensitivity of 100%, specificity 85% and diagnostic accuracy of 93.5%.
      Thermography also revealed characteristic temperature patterns for fibrotic
      livers compared to healthy livers. Current data suggest that Raman spectroscopy
      and thermography could be used to detect fibrosis in ex vivo liver samples.

PMID- 28754543
TI  - Syndesmis aethopharynx (Umagillidae, Rhabdocoela, Platyhelminthes) from the sea
      urchin Paracentrotus lividus: First record from the Eastern Mediterranean,
      phylogenetic position and intraspecific morphological variation.
AB  - Specimens of Syndesmis aethopharynx Westervelt & Kozloff, 1990 (Umagillidae,
      Rhabdocoela, Platyhelminthes) were collected from the intestine of several
      specimens of the sea urchin Paracentrotus lividus (Lamarck, 1816) [2], Hansson,
      2001 at the Greek coast. This represents the first report of a species of
      Syndesmis from Greece. Our study has revealed several previously-unreported
      morphological details and intraspecific variation, which are added to the species
      description. The position of S. aethopharynx within Umagillidae is confirmed for
      the first time through molecular data (based on nuclear 18S rDNA), using both
      Bayesian and maximum likelihood analyses.

PMID- 28754544
TI  - Consensus Report by Pediatric Acute Lung Injury and Sepsis Investigators and
      Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees:
      Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children
      and Adolescents, Part 1: Focus on Investigations, Prophylaxis, and Specific
      Treatment.
AB  - Veno-occlusive disease (VOD) is a common and potentially fatal complication in
      children undergoing hematopoietic cell transplantation (HCT). It occurs in about
      one-third of all patients undergoing transplantation and is fatal in 50% of
      patients with severe disease. Early intervention and specific treatment with
      defibrotide are associated with improved outcomes. However, there is a lack of
      supportive care guidelines for management of the multiorgan dysfunction seen in
      most cases. There is high variability in the management of VOD, which may
      contribute to the increased morbidity and mortality. Although there is ample
      research in the specific treatment of VOD, there is paucity of literature
      regarding the management of ascites, transfusions requirements, fluids and
      electrolyte dysfunction, delirium, and investigations in children with VOD. The
      joint working committees of the Pediatric Acute Lung Injury and Sepsis
      Investigators and the Pediatric Blood and Marrow Transplantation Consortium
      collaborated to develop a series of evidence-based supportive care guidelines for
      management of VOD. The quality of evidence was rated and recommendations were
      made using Grading of Recommendations, Assessment, Development and Evaluation
      criteria. This manuscript is part 1 of the series and focuses on the need to
      develop these guidelines; methodology used to establish the guidelines; and
      investigations needed for diagnosis, prophylaxis, and treatment of VOD in
      children.

PMID- 28754545
TI  - Major Histocompatibility Mismatch and Donor Choice for Second Allogeneic Bone
      Marrow Transplantation.
AB  - Large alternative donor pools provide the potential for selecting a different
      donor for a second allogeneic (allo) bone or marrow transplant (BMT). As HLA
      disparity may contribute to the graft-versus-tumor effect, utilizing new
      mismatched haplotype donors may potentially improve the antitumor activity for
      relapsed hematologic malignancies despite a previous alloBMT. Data from patients
      who received a second alloBMT for relapsed hematologic malignancies at Johns
      Hopkins were analyzed. Outcomes were compared between patients who received a
      second allograft with the same MHC composition and those who received an
      allograft with a new mismatched haplotype. Loss of heterozygosity analysis was
      performed for patients with acute myeloid leukemia (AML) whose first allograft
      was haploidentical. Between 2005 and 2015, 40 patients received a second BMT for
      a relapsed hematologic malignancy. The median follow-up is 750 (range, 26 to
      2950) days. The median overall survival (OS) in the cohort is 928 days (95%
      confidence interval [CI], 602 to not reached [NR]); median event-free survival
      (EFS) for the cohort is 500 days (95% CI, 355 to NR). The 4-year OS is 40% (95%
      CI, 25% to 64%), and the 4-year EFS is 36% (95% CI, 24% to 55%). The cumulative
      incidence of nonrelapsed mortality by 2 years was 27% (95% CI, 13% to 42%). The
      cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) at
      100 days was 15% (95% CI, 4% to 26%); the cumulative incidence of extensive
      chronic GVHD at 2 years was 22% (95% CI, 9% to 36%). The median survival was 552
      days (95% CI, 376 to 2950+) in the group who underwent transplantation with a
      second allograft that did not harbor a new mismatched haplotype, while it was not
      reached in the group whose allograft contained a new mismatched haplotype (hazard
      ratio [HR], .36; 95% CI, .14 to .9; P = .02). EFS was also longer in the group
      who received an allograft containing a new mismatched haplotype, (NR versus 401
      days; HR, .50; 95% CI, .22 to 1.14; P = .09). Although the allograft for this
      patient's second BMT contained a new mismatched haplotype, AML nevertheless
      relapsed a second time. Second BMTs are feasible and provide a reasonable chance
      of long-term survival. An allograft with a new mismatched haplotype may improve
      outcomes after second BMTs for relapsed hematologic malignancies.

PMID- 28754546
TI  - Comparison of Different Stem Cell Mobilization Regimens in AL Amyloidosis
      Patients.
AB  - High-dose melphalan (HDM) and autologous blood stem cell transplantation (ABSCT)
      is an effective treatment for transplantation-eligible patients with systemic
      light chain (AL) amyloidosis. Whereas most centers use granulocyte colony
      stimulating factor (G-CSF) alone for mobilization of peripheral blood stem cells
      (PBSC), the application of mobilization chemotherapy might offer specific
      advantages. We retrospectively analyzed 110 patients with AL amyloidosis who
      underwent PBSC collection. Major eligibility criteria included age <70 years and
      cardiac insufficiency New York Heart Association <=III degrees . Before
      mobilization, 67 patients (61%) had been pretreated with induction therapy,
      including 17 (15%) patients who had received melphalan. Chemo-mobilization was
      performed with either cyclophosphamide, doxorubicin, dexamethasone (CAD)/G-CSF (n
      = 78, 71%); ifosfamide/G-CSF (n = 14, 13%); or other regimens (n = 8, 7%). AL
      amyloidosis patients with predominant heart involvement and/or status post heart
      transplantation were mobilized with G-CSF only (n = 10, 9%). PBSC collection was
      successful in 101 patients (92%) at first attempt. The median number of CD34+
      cells was 8.7 (range, 2.1 to 45.5) * 106 CD34+/kg collected in a median of 1
      leukapheresis (LP) session. Compared with G-CSF-only mobilization, a chemo
      mobilization with CAD/G-CSF or ifosfamide/G-CSF had a positive impact on the
      number of collected CD34+ cell number/kg per LP (P <.001, multivariate).
      Melphalan-containing previous therapy and higher age had a significant negative
      impact on quantity of collected CD34+ cells. Median common toxicity criteria
      (CTC) grade of nonhematologic toxicity was II (range, 0 to IV). Life-threatening
      CTC grade IV adverse events were observed in 3 patients with no fatalities.
      Cardiovascular events were observed in 17 patients (22%) upon CAD/G-CSF
      mobilization (median CTC: grade 3; range, 1 to 4). Toxicity in patients
      undergoing ifosfamide/G-CSF mobilization was higher than in with those who
      received G-CSF-only mobilization. HDM and ABSCT were performed in 100 patients.
      Compared with >6.5 * 106 transplanted CD34+ cells/kg, an ABSCT with <3 * 106
      CD34+ cells/kg was associated with a longer duration to leukocyte reconstitution
      >1 * 109/L and a reduced platelet count <150 * 109/L 1 year after ASCT. Our
      results show that CAD chemotherapy is very effective in PBSC mobilization and has
      a tolerable toxicity profile in AL amyloidosis patients. A further toxicity
      reduction by omission of doxorubicin might be considered. Because of advanced
      nonhematologic toxicity, ifosfamide administration cannot be recommended.
      However, G-CSF mobilization alone is also safe and effective. Considering the
      hematopoietic reconstitution and long-term stem cell function, our results
      provide a rationale to collect and transplant as many as >6.5 * 106 CD34+
      cells/kg, if feasible with reasonable effort.

PMID- 28754547
TI  - First birth following spindle transfer.

PMID- 28754548
TI  - Impact of the outcome of fresh blastocyst transfer on the subsequent frozen
      thawed blastocyst transfer cycle.
AB  - The objective of this observational study was to assess the influence of the
      outcome of fresh blastocyst transfer on the success rate of the subsequent
      sibling frozen-thawed blastocyst transfer (FBT) cycle. In total, 1639 FBT cycles
      were divided into two groups: Group A (n = 698) cycles in which a positive
      pregnancy test result was achieved and Group B (n = 941) cycles in which no
      pregnancy was achieved in the preceding fresh IVF cycle. Mean age at
      cryopreservation, basal FSH level, number of oocytes retrieved, number of embryos
      transferred in the fresh cycle and survival rate of the thawed blastocysts in the
      FBT cycle were comparable between the two groups. Although significantly more
      thawed blastocysts were transferred in the FBT cycles in Group B compared with
      Group A, the live birth rate in Group A was significantly higher compared with
      Group B. After adjusting for potentially confounding variables, the likelihood of
      a live birth after FBT was significantly higher when a pregnancy was achieved in
      the preceding fresh IVF cycle. Achieving a pregnancy after fresh blastocyst
      transfer is an independent factor influencing the outcome of the subsequent
      sibling FBT.

PMID- 28754549
TI  - Complexity Levels in Patients With Heart Failure Diagnostic Codes in a
      Population.

PMID- 28754550
TI  - Thoracic Aortitis Due to Salmonella enteritidis.

PMID- 28754551
TI  - The fragility of significant results underscores the need of larger randomized
      controlled trials in nephrology.
AB  - The Fragility Index is a tool for testing robustness of randomized controlled
      trial results for dichotomous outcomes. It describes the minimum number of
      individuals in whom changing an event status would render a statistically
      significant result nonsignificant. Here we identified all randomized controlled
      trials in five nephrology and five general journals from 2005-2014. A total of
      127 randomized controlled trials reporting at least one dichotomous statistically
      significant outcome (p less than 0.05) were included and the Fragility Index was
      calculated. Twenty randomized controlled trials had a Fragility Index of zero and
      were excluded from further analysis. Linear regression was performed to assess
      factors associated with Fragility Indexes stratified by primary or secondary
      outcomes. The median sample size was 134 (range 2211506) with 36 (range 5-2743)
      total number of events. The median Fragility Index was three (range 1-166),
      indicating that in half the trials the addition of three events to the treatment
      with the lowest number of events rendered the result nonsignificant. For primary
      outcome studies a doubling in total event number and sample size significantly
      increased the geometric mean Fragility Index by 52% and 42%, respectively.
      Compared to a reported p value of 0.05 to 0.01, those reporting 0.01 to 0.001 or
      less than 0.001 had a significant 57% and 472% increase in the median Fragility
      Index, respectively. Forty-one percent had a Fragility Index less than the total
      loss to follow-up, indicating a potential to change a trial result had all
      individuals been accounted for. Thus, our study highlights the need for larger
      randomized controlled trials with accurate accounting for loss to follow-up to
      adequately guide evidence-based practice.

PMID- 28754552
TI  - Ubiquitin C-Terminal Hydrolase L1 is required for regulated protein degradation
      through the ubiquitin proteasome system in kidney.
AB  - Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a major deubiquitinating enzyme of
      the nervous system and associated with the development of neurodegenerative
      diseases. We have previously shown that UCH-L1 is found in tubular and parietal
      cells of the kidney and is expressed de novo in injured podocytes. Since the role
      of UCH-L1 in the kidney is unknown we generated mice with a constitutive UCH-L1
      deficiency to determine its role in renal health and disease. UCH-L1-deficient
      mice developed proteinuria, without gross changes in glomerular morphology.
      Tubular cells, endothelial cells, and podocytes showed signs of stress with an
      accumulation of oxidative-modified and polyubiquitinated proteins.
      Mechanistically, abnormal protein accumulation resulted from an altered
      proteasome abundance leading to decreased proteasomal activity, a finding
      exaggerated after induction of anti-podocyte nephritis. UCH-L1-deficient mice
      exhibited an exacerbated course of disease with increased tubulointerstitial and
      glomerular damage, acute renal failure, and death, the latter most likely a
      result of general neurologic impairment. Thus, UCH-L1 is required for regulated
      protein degradation in the kidney by controlling proteasome abundance. Altered
      proteasome abundance renders renal cells, particularly podocytes and endothelial
      cells, susceptible to injury.

PMID- 28754553
TI  - Real-time in vivo mitochondrial redox assessment confirms enhanced mitochondrial
      reactive oxygen species in diabetic nephropathy.
AB  - While increased mitochondrial reactive oxygen species have been commonly
      implicated in a variety of disease states, their in vivo role in the pathogenesis
      of diabetic nephropathy remains controversial. Using a two-photon imaging
      approach with a genetically encoded redox biosensor, we monitored mitochondrial
      redox state in the kidneys of experimental models of diabetes in real-time in
      vivo. Diabetic (db/db) mice that express a redox-sensitive Green Fluorescent
      Protein biosensor (roGFP) specifically in the mitochondrial matrix (db/dbmt
      roGFP) were generated, allowing dynamic monitoring of redox changes in the
      kidneys. These db/dbmt-roGFP mice exhibited a marked increase in mitochondrial
      reactive oxygen species in the kidneys. Yeast NADH-dehydrogenase, a mammalian
      Complex I homolog, was ectopically expressed in cultured podocytes, and this
      forced expression in roGFP-expressing podocytes prevented high glucose-induced
      increases in mitochondrial reactive oxygen species. Thus, in vivo monitoring of
      mitochondrial roGFP in diabetic mice confirms increased production of
      mitochondrial reactive oxygen species in the kidneys.

PMID- 28754554
TI  - Impairment of the carnitine/organic cation transporter 1-ergothioneine axis is
      mediated by intestinal transporter dysfunction in chronic kidney disease.
AB  - Carnitine/organic cation transporter 1 (OCTN1) is a specific transporter of the
      food-derived antioxidant ergothioneine. Ergothioneine is absorbed by intestinal
      OCTN1, distributed through the bloodstream, and incorporated into each organ by
      OCTN1. OCTN1 expression is upregulated in injured tissues, and promotes
      ergothioneine uptake to reduce further damage caused by oxidative stress.
      However, the role of the OCTN1-ergothioneine axis in kidney-intestine cross-talk
      and chronic kidney disease (CKD) progression remains unclear. Here we assessed
      ergothioneine uptake via intestinal OCTN1 and confirmed the expression of OCTN1.
      The ability of OCTN1 to absorb ergothioneine was diminished in mice with CKD. In
      combination with OCTN1 dysfunction, OCTN1 localization on the intestinal apical
      cellular membrane was disturbed in mice with CKD. Proteomic analysis, RT-PCR,
      Western blotting, and immunohistochemistry revealed that PDZ (PSD95, Dlg, and
      ZO1), a PDZK1 domain-containing protein that regulates the localization of
      transporters, was decreased in mice with CKD. Decreased intestinal ergothioneine
      uptake from food decreased ergothioneine levels in the blood of mice with CKD.
      Despite increased OCTN1 expression and ergothioneine uptake into the kidneys of
      mice with CKD, ergothioneine levels did not increase. To identify the role of the
      OCTN1-ergothioneine axis in CKD, we evaluated kidney damage and oxidative stress
      in OCTN1-knockout mice with CKD and found that kidney fibrosis worsened.
      Oxidative stress indicators were increased in OCTN1-knockout mice. Moreover,
      ergothioneine levels in the blood of patients with CKD decreased, which were
      restored after kidney transplantation. Thus, a novel inter-organ interaction
      mediated by transporters is associated with CKD progression.

PMID- 28754555
TI  - Elastin insufficiency causes hypertension, structural defects and abnormal
      remodeling of renal vascular signaling.
AB  - Elastin deficiency causes vascular stiffening, a leading risk for hypertension
      and chronic kidney disease (CKD). The mechanisms mediating hypertension and/or
      CKD pathogenesis due to elastin deficiency are poorly understood. Using the
      elastin heterozygous (Eln+/-) mouse model, we tested whether renal dysfunction
      due to elastin deficiency occurs independently of and precedes the development of
      hypertension. We assessed blood pressure and renal hemodynamics in 30-day and 12
      week-old male and female mice. At P30, blood pressure of Eln+/- mice was similar
      to wild-type controls; however, renal blood flow was lower, whereas renal
      vascular resistance was augmented at baseline in Eln+/- mice. At 12 weeks, renal
      vascular resistance remained elevated while filtration fraction was higher in
      male Eln+/- relative to wild-type mice. Heterozygous mice showed isolated
      systolic hypertension that was evident only at nighttime. Acute salt loading with
      6% dietary sodium increased daytime systolic blood pressure only in male Eln+/-
      mice, causing a rightward shift and blunted slope of the pressure-natriuresis
      curve. Renal interlobar artery basal tone and myogenic response to increasing
      intraluminal pressure at day 10 were similar, whereas they were augmented at day
      30 and at 12 weeks old in Eln+/- mice, and normalized by the AT1R blocker,
      candesartan. Heterozygous mice also exhibited podocyte foot process damage that
      persisted even when blood pressure was normalized to wild-type levels with
      hydralazine. Thus, elastin insufficiency triggers structural defects and abnormal
      remodeling of renal vascular signaling involving AT1R-mediated vascular
      mechanotransduction and renal hyperfiltration with increased blood pressure
      sensitivity to dietary sodium contributing to systolic hypertension.

PMID- 28754556
TI  - Kidney function is associated with an altered protein composition of high-density
      lipoprotein.
AB  - Patients with chronic kidney disease (CKD) exhibit a myriad of metabolic
      derangements, including dyslipidemia characterized by low plasma concentrations
      of high-density lipoprotein (HDL)-associated cholesterol. However, the effects of
      kidney disease on HDL composition have not been comprehensively determined. Here
      we used a targeted mass spectrometric approach to quantify 38 proteins contained
      in the HDL particles within a CKD cohort of 509 participants with a broad range
      of estimated glomerular filtration rates (eGFRs) (CKD stages I-V, and a mean eGFR
      of 45.5 mL/min/1.73m2). After adjusting for multiple testing, demographics,
      comorbidities, medications, and other characteristics, eGFR was significantly
      associated with differences in four HDL proteins. Compared to participants with
      an eGFR of 60 mL/min/1.73m2 or more, those with an eGFR under 15 mL/min/1.73m2
      exhibited 1.89-fold higher retinol-binding protein 4 (95% confidence interval
      1.34-2.67), 1.52-fold higher apolipoprotein C-III (1.25-1.84), 0.70-fold lower
      apolipoprotein L1 (0.55-0.92), and 0.64-fold lower vitronectin (0.48-0.85).
      Although the HDL apolipoprotein L1 was slightly lower among African Americans
      than among Caucasian individuals, the relationship to eGFR did not differ by
      race. After adjustment, no HDL-associated proteins associated with albuminuria.
      Thus, modest changes in the HDL proteome provide preliminary evidence for an
      association between HDL proteins and declining kidney function, but this needs to
      be replicated. Future analyses will determine if HDL proteomics is indeed a
      clinical predictor of declining kidney function or cardiovascular outcomes.

PMID- 28754557
TI  - Accelerated podocyte detachment and progressive podocyte loss from glomeruli with
      age in Alport Syndrome.
AB  - Podocyte depletion is a common mechanism driving progression in glomerular
      diseases. Alport Syndrome glomerulopathy, caused by defective alpha3alpha4alpha5
      (IV) collagen heterotrimer production by podocytes, is associated with an
      increased rate of podocyte detachment detectable in urine and reduced glomerular
      podocyte number suggesting that defective podocyte adherence to the glomerular
      basement membrane might play a role in driving progression. Here a genetically
      phenotyped Alport Syndrome cohort of 95 individuals [urine study] and 41 archived
      biopsies [biopsy study] were used to test this hypothesis. Podocyte detachment
      rate (measured by podocin mRNA in urine pellets expressed either per creatinine
      or 24-hour excretion) was significantly increased 11-fold above control, and
      prior to a detectably increased proteinuria or microalbuminuria. In parallel,
      Alport Syndrome glomeruli lose an average 26 podocytes per year versus control
      glomeruli that lose 2.3 podocytes per year, an 11-fold difference corresponding
      to the increased urine podocyte detachment rate. Podocyte number per glomerulus
      in Alport Syndrome biopsies is projected to be normal at birth (558/glomerulus)
      but accelerated podocyte loss was projected to cause end-stage kidney disease by
      about 22 years. Biopsy data from two independent cohorts showed a similar
      estimated glomerular podocyte loss rate comparable to the measured 11-fold
      increase in podocyte detachment rate. Reduction in podocyte number and density in
      biopsies correlated with proteinuria, glomerulosclerosis, and reduced renal
      function. Thus, the podocyte detachment rate appears to be increased from birth
      in Alport Syndrome, drives the progression process, and could potentially help
      predict time to end-stage kidney disease and response to treatment.

PMID- 28754558
TI  - Magnetic resonance T2 mapping and diffusion-weighted imaging for early detection
      of cystogenesis and response to therapy in a mouse model of polycystic kidney
      disease.
AB  - Polycystic kidney disease (PKD) is among the leading causes of end-stage renal
      disease. Increasing evidence exists that molecular therapeutic strategies
      targeted to cyst formation and growth might be more efficacious in early disease
      stages, highlighting the growing need for sensitive biomarkers. Here we apply
      quantitative magnetic resonance imaging techniques of T2 mapping and diffusion
      weighted imaging in the jck mouse model for PKD using a clinical 3.0 T scanner.
      We tested whether kidney T2 values and the apparent diffusion coefficient (ADC)
      are superior to anatomical imaging parameters in the detection of early
      cystogenesis, as shown on macro- and histopathology. We also tested whether
      kidney T2 values and ADC have the potential to monitor early treatment effects of
      therapy with the V2 receptor antagonist Mozavaptane. Kidney T2 values and to a
      lesser degree ADC were found to be highly sensitive markers of early cystogenesis
      and superior to anatomical-based imaging parameters. Furthermore, kidney T2
      values exhibited a nearly perfect correlation to the histological cystic index,
      allowing a clear separation of the two mouse genotypes. Additionally, kidney T2
      values and ADC were able to monitor early treatment effects in the jck mouse
      model in a proof-of-principle experiment. Thus, given the superiority of kidney
      T2 values and ADC over anatomical-based imaging in mice, further studies are
      needed to evaluate the translational impact of these techniques in patients with
      PKD.

PMID- 28754559
TI  - Enzymatic cleavage promotes disassembly of GII.3 norovirus virus like particles
      and its binding to salivary histo-blood group antigens.
AB  - In this study, we found that addition of fecal extract significantly promoted the
      binding of GII.3 NoV VLPs to salivary HBGAs. SDS-PAGE analysis indicated that
      major capsid proteins (VP1) were cleaved into two major bands with molecular
      weights of 26 and 31kD, respectively. Pretreatment of fecal extract by boiling or
      addition of protease inhibitor cocktail or type specific protease inhibitor
      (leupeptin and aprotinin) during incubation all decreased VP1 cleavage and its
      binding to salivary HBGAs. Trypsin digestion led to cleavage of VP1 and promoted
      its binding to HBGAs, suggesting that the active enzyme(s) might be trypsin or
      trypsin-like enzymes. Trypsin and fecal extract pretreatment all led to loss of
      morphological intact VLPs, indicating enhanced signal was possible due to
      increased binding of fragmented subunits. N-terminal sequencing was performed to
      characterize the cleavage sites with indecisive results. In vitro VLP-salivary
      HBGAs binding blockade assay using VLPs derived from VP1 of different GII.3
      strains and rabbit anti-genotype specific hyperimmune serum indicated that GII.3
      NoVs might have conservative HBGA binding sites. In summary, our results provide
      evidence about the widespread presence of active enzyme in fecal samples that can
      cleave GII.3 NoV VLPs and demonstrate that GII.3 NoVs have conservative HBGA
      binding sites which might have implications in the design of multivalent NoV
      vaccines.

PMID- 28754560
TI  - Correlation of cellular factors and differential scrapie prion permissiveness in
      ovine microglia.
AB  - Prion diseases are fatal neurodegenerative disorders by which the native cellular
      prion protein (PrPC) is misfolded into an accumulating, disease-associated
      isoform (PrPD). To improve the understanding of prion pathogenesis and develop
      effective treatments, it is essential to elucidate factors contributing to
      cellular permissiveness. We previously isolated five clones from an immortalized
      subline of ovine microglia, two of which had demonstrated differential
      permissiveness to a natural isolate of sheep scrapie and distinct transcriptomic
      profiles. To more robustly identify factors contributing to this activity,
      relative permissiveness, cell proliferation, selected gene transcript level, and
      matrix metalloproteinase 2 (MMP2) activity were compared amongst all five clones.
      Differences in cell proliferation were not detected between clones; however,
      significant correlations were identified between relative permissiveness and
      genes associated with cell growth (i.e., RARRES1 and PTN), protein degradation
      (i.e., CTSB and SQSTM1), and heparin binding (i.e., SEPP1). MMP2 activity varied
      amongst clones, but did not correlate with permissiveness. These associations
      support the contribution of cell division and protein degradation on the
      permissiveness of cultured ovine microglia to PrPD.

PMID- 28754561
TI  - The NSm proteins of phylogenetically related tospoviruses trigger Sw-5b-mediated
      resistance dissociated of their cell-to-cell movement function.
AB  - The cell-to-cell movement protein (NSM) of tomato spotted wilt virus (TSWV) has
      been recently identified as the effector of the single dominant Sw-5b resistance
      gene from tomato (Solanum lycopersicum L.). Although most TSWV isolates shows a
      resistance-inducing (RI) phenotype, regular reports have appeared on the
      emergence of resistance-breaking (RB) isolates in tomato fields, and suggested a
      strong association with two point mutations (C118Y and T120N) in the NSM protein.
      In this study the Sw-5b gene has been demonstrated to confer not only resistance
      against TSWV but to members of five additional, phylogenetically-related
      classified within the so-called "American" evolutionary clade, i.e., Alstroemeria
      necrotic streak virus (ANSV), chrysanthemum stem necrosis virus (CSNV), groundnut
      ringspot virus (GRSV), Impatiens necrotic spot virus (INSV) and tomato chlorotic
      spot virus (TCSV). Remarkably, bean necrotic mosaic virus (BeNMV), a recently
      discovered tospovirus classified in a distinct American subclade and circulating
      on the American continent, did not trigger a Sw-5b-mediated hypersensitive (HR)
      response. Introduction of point mutations C118Y and T120N into the NSM protein of
      TSWV, TCSV and CSNV abrogated the ability to trigger Sw-5b-mediated HR in both
      transgenic-N. benthamiana and tomato isolines harboring the Sw-5b gene whereas it
      had no effect on BeNMV NSM. Truncated versions of TSWV NSM lacking motifs
      associated with tubule formation, cell-to-cell or systemic viral movement were
      made and tested for triggering of resistance. HR was still observed with
      truncated NSM proteins lacking 50 amino acids (out of 301) from either the amino-
      or carboxy-terminal end. These data altogether indicate the importance of amino
      acid residues C118 and T120 in Sw-5b-mediated HR only for the NSM proteins from
      one cluster of tospoviruses within the American clade, and that the ability to
      support viral cell-to-cell movement is not required for effector functionality.

PMID- 28754562
TI  - Molecular investigation on the binding of Cd(II) by the binary mixtures of
      montmorillonite with two bacterial species.
AB  - Bacteria-phyllosilicate complexes are commonly found in natural environments and
      are capable of immobilizing trace metals. However, the molecular binding
      mechanisms of heavy metals to these complex aggregates still remain poorly
      understood. This study investigated Cd adsorption on Gram-positive Bacillus
      subtilis, Gram-negative Pseudomonas putida and their binary mixtures with
      montmorillonite using surface complexation model, Cd K-edge extended X-ray
      absorption fine structure (EXAFS) spectroscopy and isothermal titration
      calorimetry (ITC). We have shown that larger amounts of Cd are adsorbed by B.
      subtilis than by P. putida at pH<~6, and Cd sorption that binding to phosphate
      groups plays a more important role in P. putida than in B. subtilis. This remind
      us that we should consider the microbe species when predict the biochemical
      behavior of trace metals in microbe-bearing environments. The observed Cd
      adsorption on the binary bacteria-clay composites was more than that predicted
      based on the component additivity approach. When taking bacteria-clay (1:1 mass
      ratio) as a representative example, an approximately 68%:32% metal distribution
      between the bacterial and mineral fraction was found. Both the EXAFS and ITC fits
      showed that the binding stoichiometry for Cd-carboxyl/phosphate was smaller in
      the binary mixtures than that in pure bacteria. We proposed that the significant
      deviations were possibly due to the physical-chemical interaction between the
      composite fractions that might reduce the agglomeration of the clay grains,
      increase the negative surface charges, and provide additional bridging of metals
      ions between bacterial cells and clays.

PMID- 28754563
TI  - Changes in gene expression variability reveal a stable synthetic lethal
      interaction network in BRCA2-ovarian cancers.
AB  - Synthetic lethal interactions (SLIs) are robust mechanisms that provide cells
      with the ability to remain viable despite having mutations in genes critical to
      the DNA damage response, a core cellular process. Studies in model organisms such
      as S. cerevisiae showed that thousands of genes important in maintaining DNA
      integrity cooperated in a SLI network. Two genes participate in a SLI when a
      mutation in one gene has no effect on the cell, but mutations in both interacting
      genes are lethal. Furthermore in C. elegans, a mutation in a critical gene that
      is important for development induced a change in expression variability in the
      synthetic lethal interactor. In cancer, targeting SLIs shows promise in
      selectively killing cancer cells. For example, targeting PARP1 is an effective
      treatment for BRCA1/2- breast and ovarian cancers. Although PARP1 is already
      identified as having a SLI with BRCA1/2-, computationally searching for other
      genes that cooperate in the SLI network could highlight genes that may have
      promise for being a cancer-specific drug target. Using RNA sequencing data for
      ovarian cancer patients with BRCA2 mutations and the R Bioconductor package
      pathVar, we showed that genes whose expression changes to an invariant, stable
      expression state are likely candidates for SLIs with BRCA2. Our results highlight
      the interactions between the genes with predicted SLIs and protein-coding genes
      that are functionally important in the DNA damage response. The method of
      analyzing expression variability to computationally identify genes with SLIs can
      be applied to query SLIs in other tumor types.

PMID- 28754564
TI  - Relationship of Extreme Cold Weather and Implantable Cardioverter Defibrillator
      Shocks.
AB  - Cold weather to 0 degrees C has been implicated as a risk factor for ventricular
      arrhythmias and implantable cardioverter defibrillator (ICD) shocks. The effect
      of more extreme cold weather on the risk of ventricular arrhythmias and ICD
      shocks is unknown. We sought to describe the relationship between extreme cold
      weather and the risk of ICD shocks. We retrospectively identified patients seen
      at the Pacemaker and Defibrillator Clinic at St. Boniface Hospital in Winnipeg,
      Manitoba, Canada between 2010 and 2015 with an ICD shock. We excluded multiple
      shocks occurring on the same day in a single patient. We collected weather data,
      and evaluated the relationship between ICD shocks and weather on the same day as
      the shock using Negative Binomial regression. Three hundred and sixty patients
      experienced a total of 1,355 shocks. When excluding multiple shocks occurring in
      a single patient on the same day, there were 756 unique shocks. The daily high
      (DH) was the strongest predictor of receiving an ICD shock. Compared with the
      warmest days (DH above 10 degrees C), shocks were 25% more common on the coldest
      days (DH below -10 degrees C), and 8% more common on cold days (DH between -10
      degrees C and 10 degrees C). This linear trend was statistically significant,
      with a p-value of 0.04. In conclusion, we found an association between extreme
      cold weather and ICD shocks.

PMID- 28754565
TI  - Impact of Left Atrial Appendage Exclusion on Cardiovascular Outcomes in Patients
      With Atrial Fibrillation Undergoing Coronary Artery Bypass Grafting (From the
      National Inpatient Sample Database).
AB  - Left atrial appendage (LAA) exclusion is performed by some surgeons in patients
      with atrial fibrillation (AF) who undergo coronary artery bypass grafting (CABG).
      However, the available evidence regarding the efficacy and safety of this
      procedure remains mixed. We queried the Nationwide Inpatient Survey Database for
      the 10-year period from 2004 to 2013. Using International Classification of
      Diseases, Ninth Edition, Clinical Modification diagnosis codes, we identified
      patients who had a diagnosis of AF and underwent a primary procedure of CABG with
      or without LAA exclusion. We then performed a 1:5 matching based on the
      CHA2DS2VASc score between patients who got LAA exclusion and those who did not
      (control group). The primary outcome was the incidence of in-hospital
      cerebrovascular events, whereas the secondary outcomes included in-hospital
      bleeding events, pericardial effusion, cardiac tamponade, postoperative shock,
      and mortality. Our analysis included a total of 15,114 patients. Patients who
      underwent LAA exclusion had significantly less incidence of cerebrovascular
      events (2.0% vs 3.1%, p = 0.002). However, LAA exclusion group had higher
      incidences of bleeding events (36.4% vs 21.3%, p <0.001), pericardial effusion
      (2.7% vs 1.2%, p <0.001), cardiac tamponade (0.6% vs 0.2%, p <0.001), and
      postoperative shock (1.2% vs 0.4%, p <0.001). LAA exclusion was associated with
      higher in-hospital mortality (1.6% vs 0.3%, p <0.001). Multivariate regression
      analysis showed that LAA exclusion was significantly associated with lower
      cerebrovascular accident events and higher in-hospital mortality. In conclusion,
      LAA exclusion in patients with AF undergoing CABG might be associated with a
      lower incidence of in-hospital cerebrovascular events. This benefit is offset by
      a higher incidence of higher bleeding events, pericardial effusion, cardiac
      tamponade, postoperative shock, and in-hospital mortality.

PMID- 28754566
TI  - Impact of Asymmetric Dimethylarginine on Coronary Physiology Early After Heart
      Transplantation.
AB  - Cardiac allograft vasculopathy is a major cause of long-term graft failure
      following heart transplantation. Asymmetric dimethylarginine (ADMA), a marker of
      endothelial dysfunction, has been mechanistically implicated in the development
      of cardiac allograft vasculopathy, but its impact on coronary physiology early
      after transplantation is unknown. Invasive indices of coronary physiology,
      namely, fractional flow reserve (FFR), the index of microcirculatory resistance,
      and coronary flow reserve, were measured with a coronary pressure wire in the
      left anterior descending artery within 8 weeks (baseline) and 1 year after
      transplant. Plasma levels of ADMA were concurrently assayed using high
      performance liquid chromatography. In 46 heart transplant recipients, there was a
      statistically significant correlation between elevated ADMA levels and lower FFR
      values at baseline (r = -0.33; p = 0.024); this modest association persisted 1
      year after transplant (r = -0.39; p = 0.0085). Patients with a baseline FFR <0.90
      (a prognostically validated cutoff) had significantly higher baseline ADMA levels
      (0.63 +/- 0.16 vs 0.54 +/- 0.12 uM; p = 0.034). Baseline ADMA (odds ratio 1.80
      per 0.1 uM; 95% confidence interval 1.07 to 3.03; p = 0.027) independently
      predicted a baseline FFR <0.90 after multivariable adjustment. Even after
      dichotomizing ADMA (>=0.60 uM, provides greatest diagnostic accuracy by receiver
      operating characteristic curve), this association remained significant (odds
      ratio 7.52, 95% confidence interval 1.74 to 32.49; p = 0.006). No significant
      relationship between ADMA and index of microcirculatory resistance or coronary
      flow reserve was detected. In conclusion, baseline ADMA was a strong independent
      predictor of FFR <0.90, suggesting that elevated ADMA levels are associated with
      abnormal epicardial function soon after heart transplantation.

PMID- 28754567
TI  - Usefulness of Pulse Amplitude Changes During the Valsalva Maneuver Measured Using
      Finger Photoplethysmography to Identify Elevated Pulmonary Capillary Wedge
      Pressure in Patients With Heart Failure.
AB  - The pulse amplitude ratio, the ratio of pulse pressure at the end of a Valsalva
      maneuver to before the onset of Valsalva, correlates with filling pressure. This
      study aimed to noninvasively estimate cardiac filling pressure in patients with
      heart failure. We developed a noninvasive handheld device to measure pulse
      amplitude ratio using finger photoplethysmography. In 69 patients who underwent
      right heart catheterization, photoplethysmography waveforms were recorded during
      a standardized Valsalva maneuver, and in 60 of these patients, pulse amplitude
      ratio was able to be calculated. Pulse amplitude ratio correlated with pulmonary
      capillary wedge pressure (PCWP) (r = 0.58, p <0.0001), particularly among those
      subjects with reduced ejection fraction (r = 0.60, p = 0.002, n = 25). A
      multivariable linear regression model for PCWP including pulse amplitude ratio,
      age, body mass index, systolic blood pressure, diastolic blood pressure, and
      heart rate yielded an R2 of 0.54. Difference in mean pulse amplitude ratio for
      subjects with a PCWP <=15 mm Hg versus >15 mm Hg was statistically significant (p
      <0.0001, area under receiver operating characteristics curve 0.79 [0.66, 0.92]).
      Pulse amplitude ratio >=0.55 predicted PCWP >15 mm Hg with 73% sensitivity and
      77% specificity. Pulse amplitude ratio also increased by an average of 0.03 with
      a leg raise maneuver (p = 0.05, n = 36). In conclusion, we demonstrate that
      noninvasively measured response to the Valsalva maneuver in patients with HF can
      estimate PCWP and also detect changes within a single patient.

PMID- 28754568
TI  - Quantifying Ischemic Risk After Percutaneous Coronary Intervention Attributable
      to High Platelet Reactivity on Clopidogrel (From the Assessment of Dual
      Antiplatelet Therapy with Drug-Eluting Stents Study).
AB  - Patients at high risk of thrombotic events after percutaneous coronary
      intervention (PCI) may potentially benefit from intensified antiplatelet therapy.
      However, more potent antiplatelet therapy would be expected to only overcome risk
      that is mediated by high platelet reactivity (PR). We used mediation analysis to
      determine the contribution of residual PR to the 2-year risk of major adverse
      cardiac events (MACE; the composite of cardiac death, myocardial infarction, or
      stent thrombosis) associated with clinical risk factors after PCI with drug
      eluting stents (DES) in 8,374 patients from the prospective, multicenter
      Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES)
      registry. Residual PR on clopidogrel, as measured by the VerifyNow P2Y12 point-of
      care assay, was included as a continuous linear mediator variable in Cox
      proportional hazards regression. Among 7 factors independently associated with 2
      year MACE, residual PR partly mediated the effect of diabetes (13.4% attributable
      risk), anemia (22.9% attributable risk), and acute coronary syndromes (7.3%
      attributable risk). A PR-mediated effect inversely affected the MACE risk
      associated with smoking (10.4% attributable risk). The increased ischemic risk of
      chronic kidney disease, multivessel disease, and previous myocardial infarction
      were not mediated by residual PR. In conclusion, high residual PR mediates little
      or none of the increased 2-year MACE risk associated with baseline risk factors
      in patients treated with clopidogrel after successful PCI with DES. Intensifying
      antiplatelet therapy is therefore unlikely to substantially mitigate the excess
      ischemic risk from these variables.

PMID- 28754569
TI  - Development of reliable detection assays for blueberry mosaic- and blackberry
      vein banding- associated viruses based on their population structures.
AB  - Blueberry mosaic associated virus (BlMaV), the presumed causal agent of the
      homonymous disease and blackberry vein banding associated virus (BVBaV), a
      component of the blackberry yellow vein disease complex, are recently
      characterized RNA viruses. There is a need for efficient and sensitive detection
      protocols for the two viruses, not only for screening during the nursery
      propagation process but also in commercial fields to better understand virus
      epidemiology and minimize disease spread. RNA viruses display significant
      nucleotide variation forming quasi-species. Therefore, sequence-based detection
      methodologies, even though sensitive, may lead to false negative results. For
      this reason, information on the genetic diversity of virus populations is
      essential to develop diagnostic assays that have the potential to detect all
      variants. Detection assays for BlMaV and BVBaV were developed based on existing
      genetic diversity data and were validated by screening samples from different
      geographical areas in the United States. These detection tests provide
      sensitivity and specificity and will serve as the protocols of choice for virus
      screening in Vaccinium and Rubus certification programs in the United States and
      elsewhere. Given the increasing global trade of both blueberry and blackberry
      these tests will be valuable in avoiding virus introductions to new areas.

PMID- 28754570
TI  - FAT 10 protein as a potential serological marker in the diagnosis of
      hepatocellullar carcinoma.

PMID- 28754571
TI  - ERE-dependent transcription and cell proliferation: Independency of these two
      processes mediated by the introduction of a sulfone function into the weak
      estrogen estrothiazine.
AB  - The synthetic coumestrol derivative 6,12-dihydro-3-methoxy-1-benzopyrano[3,4
      b][1,4]benzothiazin-6-one (estrothiazine, ESTZ) has been identified as a weak
      estrogen receptor alpha (ERalpha) ligand unable to compete with tritiated
      estradiol. The biological activity of this compound, supported by a methoxy group
      in position 3, seems mainly to result from its capacity to activate ERalpha
      dimerization without any participation of coactivators. In support of this view
      and referring to conventional estrogens, an ESTZ metabolism study conducted with
      hepatic human microsomes failed to provide any argument in favour of an
      estrogenic activity dependent on a metabolic conversion of the compound into
      hydroxylated metabolites with strong receptor activation ability. Interestingly,
      we failed to detect any oxidation of the sulfur atom of the compound. In the
      light of pharmacological literature data concerning sulfonylation, we assessed
      ERalpha-mediated activities generated by two sulfonylated ESTZ derivatives in
      which the methoxy group that plays a key role in its mechanism of action was
      maintained or removed. Sulfonylated ESTZ, even in its demethoxylated form,
      induced ERE-mediated transcriptions in MCF-7 breast cancer cells, without
      affecting the ERalpha turnover rate. In contrast to ESTZ, this compound failed to
      enhance the proliferation of ERalpha-positive breast cancer cells, suggesting
      that its sulfone function confers upon the receptor a capacity to elicit some of
      the known characteristics associated with estrogenic responses. Moreover, we
      demonstrated that this sulfone may contribute to ERalpha dimerization without any
      requirement of the methoxy group. Nevertheless, it seems to cooperate with this
      group, as reflected by a weak ability of the sulfonylated form of ESTZ to compete
      with tritiated estradiol for ERalpha-binding. Assessment of the docking of this
      compound within the ligand-binding domain of the receptor by molecular dynamics
      provided an explanation for this observation since the sulfone is engulfed in a
      small hydrophobic pocket involving the residues Leu-346, Leu-349, Ala-350 and Leu
      384, also known to recruit coactivators. This work not only reports the sulfone
      functional group as a pharmacophore for estrogenic activity, but also opens new
      perspectives for the development of estrogenic molecules with therapeutic purpose
      and devoid of proliferative side effects.

PMID- 28754572
TI  - The formation process and responsive impacts of single oil droplet in submerged
      process.
AB  - Simulated column was applied to research forming progress of single oil droplet
      in submerged process, floating progress, and study effects of environment factors
      and dispersants on the concentration of oil hydrocarbon in water as well as
      changing rules of oil droplet sizes. As expected, particular formation mechanism
      of single oil droplet was presented. When necking down length L is 0.5 time of
      oil droplet diameter (d) after expansion phase, necking down becomes long and
      thin; when L=2d, necking down begins to break. In floating progress, the shape
      changes oval and its motion trail becomes an auger-type. Fluctuation occurs at
      horizontal direction. Dispersants decrease oil droplet size by its dispersion
      effect, and cut down effect of Van Der Waals force among oil droplets. More
      broadly, these findings provide rare empirical evidence expounding formation
      mechanism of single oil droplet to increasing ability of oil spill response.

PMID- 28754573
TI  - Enhanced microbubbles assisted cleaning of diesel contaminated sand.
AB  - In this article, we investigated the effect of low intensity pulsed ultrasound
      (US), temperature and salinity on cleaning efficacy of fine bubbles with diameter
      <50MUm for diesel contaminated sands. About 47% and 76% diesel removal was
      achieved from 10% (w/w) diesel contaminated fine and medium sands respectively,
      after 30min treatment with 40kHz low intensity intermittent pulsed US together
      with MBs in contrast to 41% and 68% diesel removal while treatment with MBs
      alone. The effect of high temperature was found to be prominent during the
      initial stages of cleaning. In addition, MBs generated in 599mM saline water
      efficiently removed 85% diesel from fine sand within 30min in contrast to only
      41% diesel removal with MBs in fresh water. This study provides evidence for
      developing highly efficient MBs based chemical free technology for diesel
      contaminated sediments.

PMID- 28754574
TI  - Effects of bark washing and epiphytic moss on 137Cs activity concentration in
      bark and stemflow in Japanese persimmon (Diospyros kaki Thunb.).
AB  - The effects of bark washing, and of epiphytic moss growing on the bark surfaces,
      on the 137Cs activity concentrations in bark and stemflow samples were evaluated
      at two Japanese persimmon orchards located in Fukushima City and Date City, both
      approximately 60-65 km northwest of the Fukushima Dai-ichi nuclear power plant.
      The means of 137Cs in stemflow captured by 1 g of sphagnum placed on the main
      trunks of washed and unwashed trees, and on sites with moss and with no moss
      growing on bark of the non-washed trees in Date City, were 0.37 Bq, 1.08Bq, 0.77
      Bq and 0.52 Bq respectively. The 137Cs was significantly lower in the washed bark
      and in the absence of moss at p = 0.00031 and p = 0.0443 by t-test respectively.
      The 137Cs in directly-collected stemflow on the main trunks was significantly
      higher for the unwashed tree at 6.0 Bq L-1 compared with the washed tree at 1.1
      Bq L-1 (p = 0.017 by Tukey's test). The extraction rate of dissolved 137Cs with
      deionized water was 7.3% even after stirring for 40 h. These results indicate
      that the moss acts as reservoir of 137Cs, and that bark-washing decontamination
      can reduce the additional 137Cs supply from moss in subsequent years following
      the radioactive fallout.

PMID- 28754575
TI  - Heterotopic bone induction via BMP signaling: Potential therapeutic targets for
      fibrodysplasia ossificans progressiva.
AB  - More than 50years ago, Marshal M. Urist detected "heterotopic bone-inducing
      activity" in demineralized bone matrix. This unique activity was referred to as
      "bone morphogenetic protein (BMP)" because it was sensitive to trypsin digestion.
      Purification of the bone-inducing activity from demineralized bone matrix using a
      bone-inducing assay in vivo indicated that the original "BMP" consisted of a
      mixture of new members of the transforming growth factor-beta (TGF-beta) family.
      The establishment of new in vitro assay systems that reflect the bone-inducing
      activity of BMPs in vivo have revealed the functional receptors and downstream
      effectors of BMPs. Fibrodysplasia ossificans progressiva (FOP) is a rare genetic
      disorder characterized by progressive heterotopic bone formation in soft tissues
      similar to the event induced by the transplantation of BMPs in skeletal muscle.
      In patients with FOP, genetic mutations have been identified in the ACVR1 gene,
      which encodes the BMP receptor ALK2. The mutations in ALK2 associated with FOP
      are hypersensitive to type II receptor kinases. Recently, activin A, a non
      osteogenic member of the TGF-beta family, was identified as the ligand of the
      mutant ALK2 in FOP, and various types of signaling inhibitors for mutant ALK2 are
      currently under development to establish effective treatments for FOP.

PMID- 28754576
TI  - [Management of odontogenic infections in Primary Care: Antibiotic?]
AB  - Our aim is to contribute to the rational use of antibiotics prescribed by family
      doctors when a patient consults for a dental problem. Nowadays we should not ask
      which antibiotic to give. The question has to be if we need to prescribe
      antibiotics in front of the most common odontogenic infections seen in our
      practice. We review the main dental infections, which should be their appropriate
      management and the role of prevention. We need to know the complexity of the oral
      microbiome because it?ll depend on the appropriateness of the antibiotherapy, the
      evolution towards cure or progression of some odontogenic infections. The
      bacterial plaque, formed by the biofilm, behaves as a barrier to the action of
      antimicrobials. It?s in the prevention of its development as well as in it
      mechanical elimination once shaped, in what the family doctor should insist. We
      must transmit antibiotics don?t heal dental pain.

PMID- 28754577
TI  - Voice Use Among Music Theory Teachers: A Voice Dosimetry and Self-Assessment
      Study.
AB  - OBJECTIVES: This study aimed (1) to investigate music theory teachers'
      professional and extra-professional vocal loading and background noise exposure,
      (2) to determine the correlation between vocal loading and background noise, and
      (3) to determine the correlation between vocal loading and self-evaluation data.
      METHODS: Using voice dosimetry, 13 music theory teachers were monitored for one
      workweek. The parameters analyzed were voice sound pressure level (SPL),
      fundamental frequency (F0), phonation time, vocal loading index (VLI), and noise
      SPL. Spearman correlation was used to correlate vocal loading parameters (voice
      SPL, F0, and phonation time) and noise SPL. Each day, the subjects self-assessed
      their voice using visual analog scales. VLI and self-evaluation data were
      correlated using Spearman correlation. RESULTS: Vocal loading parameters and
      noise SPL were significantly higher in the professional than in the extra
      professional environment. Voice SPL, phonation time, and female subjects' F0
      correlated positively with noise SPL. VLI correlated with self-assessed voice
      quality, vocal fatigue, and amount of singing and speaking voice produced.
      CONCLUSIONS: Teaching music theory is a profession with high vocal demands. More
      background noise is associated with increased vocal loading and may indirectly
      increase the risk for voice disorders. Correlations between VLI and self
      assessments suggest that these teachers are well aware of their vocal demands and
      feel their effect on voice quality and vocal fatigue. Visual analog scales seem
      to represent a useful tool for subjective vocal loading assessment and associated
      symptoms in these professional voice users.

PMID- 28754578
TI  - Reliability and Validation of the Turkish Version of the Pediatric Voice-Related
      Quality of Life Survey.
AB  - OBJECTIVE: To evaluate the effect of dysphonia in children, several methods have
      been developed, including the Pediatric Voice Outcome Survey, the Pediatric Voice
      Handicap Index, and the Pediatric Voice-Related Quality of Life (PVRQOL) Survey.
      The aim of this study was to analyze the validity of the Turkish version of the
      PVRQOL Survey. METHODS: The PVRQOL Survey consists of 10 questions that evaluate
      the effects of dysphonia on quality of life. We translated it into Turkish by
      working with two translators and faculty from the English Grammar and Literature
      Department. The Turkish version was translated back into English by two bilingual
      individuals to assess accuracy. The final version was tested by 15 parents for
      pilot study. Following the pilot study, we enrolled 52 children who had been
      admitted to the outpatient clinic with dysphonia and 79 children who had no voice
      complaints. The parents of the children under 7 years were asked to answer the
      survey. Children aged between 7 and 9 years completed the survey with their
      parents, and children over 9 years completed the survey by themselves. RESULTS:
      The results of the pilot study revealed no difference between the two groups.
      Intergroup comparisons revealed that there were statistically significant
      differences between the control and patient groups in terms of question
      responses. When the total scores of the two groups were compared, there was a
      significant difference. CONCLUSION: The Turkish version is a valid and reliable
      instrument for assessing dysphonic patients and healthy subjects.

PMID- 28754579
TI  - Rapid Discharge to Home After Total Knee Arthroplasty Is Safe in Eligible
      Medicare Patients.
AB  - BACKGROUND: This study was aimed at assessing the risk of readmission for
      Medicare patients discharged home within a day of total knee arthroplasty (TKA)
      compared to those discharged on day 2 or beyond in a community medical center.
      METHODS: A hospital inpatient database was queried for all unilateral, primary
      TKAs performed on patients 65 years or older from January 1, 2013, to December
      31, 2015. A total of 2287 patients met the study criteria, of which 1502 were
      discharged within a day (short stay), and 785 were discharged on day 2 or beyond
      (traditional stay). The main outcome measures were all-cause 30-day and unplanned
      90-day readmissions. RESULTS: Short-stay patients did not experience a higher 30
      day readmission rate (1.1%) compared to the traditional-stay patients (2.7%), nor
      did they experience a higher rate of unplanned 90-day readmissions (1.7% vs
      3.6%). The short-stay group had more favorable demographics compared to the
      traditional-stay group. Logistic regression results revealed that none of the
      demographic factors considered had a statistically significant impact on 30-day
      readmission odds for either group. For unplanned 90-day readmissions, the results
      showed that for the short-stay patients, with the exception of age, none of the
      other demographic factors had significant impact on readmission odds and none
      were significant for the traditional-stay group. CONCLUSION: Our results suggest
      that the Medicare patients meeting discharge criteria and discharged home within
      a day of TKA do not have an increased risk of 30-day and 90-day readmission.

PMID- 28754580
TI  - Microstructure and Surface Damage in Retrieved Metal-on-Metal Hip Arthroplasties.
AB  - BACKGROUND: Besides promising results of metal-on-metal (MOM) hip arthroplasty
      (HA), frequent failures have been reported even in the short term. Many host,
      surgical, design, metallurgical, and processing factors have been evoked in the
      base of these events. We have tried to characterize and to evaluate metallurgical
      and processing features present in this type of implants. METHODS: The acetabular
      and femoral components of 20 MOM HAs collected from a multicenter retrieval
      program were examined. All the specimens were inspected with naked eye, with
      confocal microscopy and vertical scanning interferometry, scanning electron
      microscopy, back-scattered electron imaging, and energy-dispersive X-ray
      spectroscopy, in 25 zones of each articular component. RESULTS: Gas pores,
      shrinkage voids and holes of detached carbides, carbides on surface, embedded
      particles, scratches and marks of wear, surface discoloration, surface deposits,
      and tribochemical reaction layers were widely dispersed through a substantial
      percentage of the total bearing surface in all the implanted components. Surface
      cup and head voids, and cup scratches showed significant correlation with the
      clearance of pair. A higher surface damage of the cup and head was observed
      mainly in the low clearance prostheses. There was no other significant
      correlation or difference in the incidence and importance of any of these defects
      between resurfacing hip arthroplasties and total hip arthroplasties, or according
      to the pair diameter. CONCLUSION: Some metallurgical features and surface damage
      were significantly present in the retrieved implants of MoM HAs. It would be
      desirable to improve the structure and metallurgical characteristics of these
      implants to avoid those effects and optimize their performance.

PMID- 28754581
TI  - Evidence for benefits in comorbid psychopathy and schizophrenia.

PMID- 28754582
TI  - Catatonia in children and adolescents: New perspectives.
AB  - INTRODUCTION: Catatonia is a rare and severe psychomotor condition in children
      and adolescents. In the current report, we aimed to review the recent literature.
      METHOD: Using a PRISMA approach, we searched MEDLINE between 1982 and 2017 using
      the keywords 'CATATONIA' and 'CHILD' or 'ADOLESCENT'. In total, we reviewed 130
      reports (controlled study, N=4; clinical chart, N=23; case report, N=54; and
      editorial/review, N=42). RESULTS: Several aspects seem to be age specific: (1)
      although the clinical presentation resembles that in adults, some symptoms are
      important in children and adolescents (e.g., psychomotor regression). (2)
      Associated disorders are similar to that found in adults; however, schizophrenia
      is more frequently observed than mood disorder. Additionally, a history of
      neurodevelopmental disorders maybe encountered. (3) Morbidity and mortality are
      among the worst in child psychiatry. (4) Underlying organic conditions are highly
      prevalent (>20% of the cases), and their search is warranted because some
      diagnoses may result in specific treatments (e.g., immune-suppressor therapy for
      autoimmune conditions). (5) Symptomatic approaches - high dose of benzodiazepines
      and electroconvulsive therapy (ECT) - are as efficient in children or adolescents
      as they are in adults, but this finding needs to be acknowledged because a
      resistance against the use of ECT or high-dose medication exists among child
      psychiatrists. DISCUSSION: Recent advances in child and adolescent catatonia
      research have offered major improvements in understanding catatonia and in new
      therapeutic opportunities. The syndrome is rare, but these advances need to be
      acknowledged in order to direct patients to centers that have developed a
      specific expertise.

PMID- 28754583
TI  - Utilising symptom dimensions with diagnostic categories improves prediction of
      time to first remission in first-episode psychosis.
AB  - There has been much recent debate concerning the relative clinical utility of
      symptom dimensions versus conventional diagnostic categories in patients with
      psychosis. We investigated whether symptom dimensions rated at presentation for
      first-episode psychosis (FEP) better predicted time to first remission than
      categorical diagnosis over a four-year follow-up. The sample comprised 193 FEP
      patients aged 18-65years who presented to psychiatric services in South London,
      UK, between 2006 and 2010. Psychopathology was assessed at baseline with the
      Positive and Negative Syndrome Scale and five symptom dimensions were derived
      using Wallwork/Fortgang's model; baseline diagnoses were grouped using DSM-IV
      codes. Time to start of first remission was ascertained from clinical records.
      The Bayesian Information Criterion (BIC) was used to find the best fitting
      accelerated failure time model of dimensions, diagnoses and time to first
      remission. Sixty percent of patients remitted over the four years following first
      presentation to psychiatric services, and the average time to start of first
      remission was 18.3weeks (SD=26.0, median=8). The positive (BIC=166.26), excited
      (BIC=167.30) and disorganised/concrete (BIC=168.77) symptom dimensions, and a
      diagnosis of schizophrenia (BIC=166.91) predicted time to first remission.
      However, a combination of the DSM-IV diagnosis of schizophrenia with all five
      symptom dimensions led to the best fitting model (BIC=164.35). Combining
      categorical diagnosis with symptom dimension scores in FEP patients improved the
      accuracy of predicting time to first remission. Thus our data suggest that the
      decision to consign symptom dimensions to an annexe in DSM-5 should be
      reconsidered at the earliest opportunity.

PMID- 28754584
TI  - Adolescent to Adult HIV Health Care Transition From the Perspective of Adult
      Providers in the United States.
AB  - PURPOSE: The HIV Care Continuum highlights the need for HIV-infected youth to be
      tested, linked, and maintained in lifelong care. Care engagement is important for
      HIV-infected youth in order for them to stay healthy, maintain a low viral load,
      and reduce further transmission. One point of potential interruption in the care
      continuum is during health care transition from adolescent- to adult-centered HIV
      care. HIV-related health care transition research focuses mainly on youth and on
      adolescent clinic providers; missing is adult clinic providers' perspectives.
      METHODS: We examined health care transition processes through semi-structured
      interviews with 28 adult clinic staff across Adolescent Trials Network sites. We
      also collected quantitative data related to clinical characteristics and
      transition-specific strategies. RESULTS: Overall, participants described health
      care transition as a "warm handoff" and a collaborative effort across adolescent
      and adult clinics. Emergent transition themes included adult clinical care
      culture (e.g., patient responsibility), strategies for connecting youth to adult
      care (e.g., adolescent clinic staff attending youth's first appointment at adult
      clinic), and approaches to evaluating transition outcomes (e.g., data sharing).
      Participants provided transition improvement recommendations (e.g., formalized
      protocols). CONCLUSIONS: Using evidence-based research and a quality improvement
      framework to inform comprehensive and streamlined transition protocols can help
      enhance the capacity of adult clinics to collaborate with adolescent clinics to
      provide coordinated and uninterrupted HIV-related care and to improve continuum
      of care outcomes.

PMID- 28754585
TI  - The Impact of the American College of Obstetricians and Gynecologists Guideline
      Changes in Pap Tests on Annual Chlamydia Test Rates.
AB  - PURPOSE: To assess impact of the 2009 American College of Obstetricians and
      Gynecologists (ACOG) Pap guideline changes on chlamydia testing rates among
      sexually active young women. METHODS: The study included sexually active women
      aged 15-25 years enrolled in commercial health plans from 2005 to 2014. We
      identified sexually active women by diagnosis, procedure, and drug codes in
      inpatient, outpatient, and drug claims databases. We identified Pap tests and
      chlamydia tests among sexually active adolescents (15-20 years) and young adults
      (21-25 years) over time. Using piecewise regression models, we compared the
      change in chlamydia testing rates before and after 2009 ACOG guidelines. RESULTS:
      From 2005 to 2014, chlamydia testing rates in sexually active women increased
      from 23% to 37% among adolescents and from 24% to 43% among young adults.
      Although the overall increase in chlamydia testing was positive, the annual rate
      of change in chlamydia testing (slope) decreased significantly after the 2009
      ACOG guideline change from 1.9% before to 1.0% after for adolescents (p < .05)
      and from 2.5% to 1.7% for young adults (p < .05). CONCLUSIONS: Although chlamydia
      test rates are increasing among sexually active women aged 15-25 years from 2005
      to 2014, the slower growth in chlamydia testing rate after 2009 may relate to the
      change in the Pap testing guidelines. Our finding that more than half of sexually
      active women aged 15-25 years did not have chlamydia testing and that the rate of
      increased chlamydia testing slowed after 2009 suggests that interventions to
      improve chlamydia testing apart from combining with Pap testing are still needed.

PMID- 28754586
TI  - Distress Associated with Dementia-Related Psychosis and Agitation in Relation to
      Healthcare Utilization and Costs.
AB  - OBJECTIVES: Explore the relationship between behavioral and psychological
      symptoms of dementia (BPSD; specifically, delusions, hallucinations, and
      agitation/aggression) and associated caregiver distress with emergency department
      (ED) utilization, inpatient hospitalization, and expenditures for direct medical
      care. DESIGN/SETTING/PARTICIPANTS: Retrospective cross-sectional cohort of
      participants with dementia (N = 332) and informants from the Aging, Demographics,
      and Memory Study, a nationally representative survey of U.S. adults >70 years
      old. MEASUREMENTS: BPSD of interest and associated informant distress
      (trichotomized as none/low/high) were assessed using the Neuropsychiatric
      Inventory (NPI). Outcomes were determined from one year of Medicare claims and
      examined according to presence of BPSD and associated informant distress,
      adjusting for participant demographics, dementia severity, and comorbidity.
      RESULTS: Fifty-eight (15%) participants with dementia had clinically significant
      delusions, hallucinations, or agitation/aggression. ED visits, inpatient
      admissions, and costs were not significantly higher among the group with
      significant BPSD. In fully adjusted models, a high level of informant distress
      was associated with all outcomes: ED visit incident rate ratio (IRR) 3.03 (95%
      CI: 1.98-4.63; p < 0.001), hospitalization IRR 2.78 (95% CI: 1.73-4.46; p <
      0.001), and relative cost ratio 2.00 (95% CI: 1.12-3.59; p = 0.02). CONCLUSIONS:
      A high level of informant distress related to participant BPSD, rather than the
      symptoms themselves, was associated with increased healthcare utilization and
      costs. Effectively identifying, educating, and supporting distressed caregivers
      may help reduce excess healthcare utilization for the growing number of older
      adults with dementia.

PMID- 28754587
TI  - 8-Hydroxy-2-deoxyguanosine ameliorates high-fat diet-induced insulin resistance
      and adipocyte dysfunction in mice.
AB  - 8-Hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, has been
      recently shown to exert anti-inflammatory effects through inhibition of Rac1.
      Inflammation in adipose tissue is a hallmark of obesity-induced insulin
      resistance, but the therapeutic potential of 8-OHdG in treatment of metabolic
      diseases has not been fully elucidated. The aim of this study was to examine the
      effect of exogenously administered 8-OHdG on adipose tissue and whole body
      metabolism. In cultured adipocytes, 8-OHdG inhibited adipogenesis and reversed
      TNFalpha-induced insulin resistance. In high-fat diet (HFD)-induced obese mice, 8
      OHdG administration blunted the rise in body weight and fat mass. The decrease in
      adipose tissue mass by 8-OHdG was due to reduced adipocyte hypertrophy through
      induction of adipose triglyceride lipase and inhibition of fatty acid synthase
      expression. 8-OHdG also inhibited the infiltration of macrophages, resulting in
      amelioration of adipose tissue inflammation and adipokine dysregulation.
      Moreover, 8-OHdG administration ameliorated adipocyte as well as systemic insulin
      sensitivity. Both in vivo and in vitro results showed that 8-OHdG induces AMPK
      activation and reduces JNK activation in adipocytes. In conclusion, our results
      show that orally administered 8-OHdG protects against HFD-induced metabolic
      disorders by regulating adipocyte metabolism.

PMID- 28754588
TI  - Substance P preserves pancreatic beta-cells in streptozotocin-induced type 1
      diabetic mice.
AB  - Preservation of the pancreatic beta-cell population is required for the
      development of therapies for diabetes, which is caused by a decrease in beta
      cells. Here, we demonstrate the antidiabetic effects of substance P (SP) in type
      1 diabetes (T1D) mice induced with streptozotocin. SP enhanced the compensatory
      proliferation of beta-cells in order to restore beta-cells in response to acute
      injury induced by a single high-dose of streptozotocin. However, SP affected
      neither the basal proliferation of beta-cells nor their apoptosis. In vitro
      studies by using the INS-1 pancreatic beta-cell line showed that SP mediated the
      increase in the proliferation of beta-cells via the activation of Akt. Chronic
      systemic treatment with SP restored the mass of beta-cells and inhibited
      insulitis in T1D mice induced with multiple low-doses of streptozotocin.
      Therefore, systemic treatment with SP may be a promising therapeutic strategy for
      treating diabetes in patients with loss of functional beta-cells.

PMID- 28754589
TI  - miR-203a controls keratinocyte proliferation and differentiation via targeting
      the stemness-associated factor DeltaNp63 and establishing a regulatory circuit
      with SNAI2.
AB  - Keratinocyte differentiation plays a pivotal role in the function of epidermal
      barrier and can be triggered by extracellular calcium in vitro and in vivo, but
      the precise mechanism still need to be further investigated. On the other hand,
      it is known that microRNAs control multiple biological events including cellular
      proliferation and differentiation. The present study demonstrated that miR-203a
      expression was upregulated in calcium-induced HaCaT Cells in a dose-dependent
      manner, whereas the stemness-associated factors SNAI2 and DeltaNp63 were
      downregulated. Furthermore, SNAI2 and DeltaNp63 were identified as the targets of
      miR-203a by computational prediction and luciferase reporter assays. The protein
      levels of SNAI2 and DeltaNp63 were suppressed by ectopic expression of miR-203a.
      Functionally, silencing of miR-203a or overexpression of SNAI2 and DeltaNp63
      attenuated cell cycle arrest induced by calcium without any changes in cellular
      apoptosis. Additionally, ectopic expression of SNAI2 inhibited miR-203a in
      calcium-induced HaCaT cells, by binding to the promoter region of miR-203a. In
      conclusion, our findings demonstrate that miR-203a plays an essential role in
      keratinocyte proliferation and differentiation caused by extracellular calcium by
      targeting the SNAI2 and DeltaNp63 genes. Furthermore, SNAI2 was found to suppress
      the transcription of miR-203a. Our data highlights a coherent cross-talk between
      two transcription factors (SNAI2 and DeltaNp63) and miR-203a in keratinocyte
      differentiation and epidermal development.

PMID- 28754590
TI  - Telmisartan mitigates hyperglycemia-induced vascular inflammation by increasing
      GSK3beta-Ser9 phosphorylation in endothelial cells and mouse aortas.
AB  - Telmisartan, an angiotensin II type 1 receptor blocker (ARB), attenuates
      hyperglycemia-aggravated vascular inflammation by decreasing IkappaB kinase beta
      (IKKbeta) expression in endothelial cells. Because glycogen synthase 3beta
      (GSK3beta) is involved in inflammatory process by regulating nuclear factor
      kappaB (NF-kappaB) activity, we investigated whether GSK3beta mediates
      telmisartan-ameliorated vascular inflammation in hyperglycemia-treated
      endothelial cells and high-fat diet (HFD)-fed mice. Telmisartan remarkably
      induced GSK3beta-Ser9 phosphorylation in hyperglycemia-treated endothelial cells
      that accompanied a decrease in hyperglycemia-induced NF-kappaB p65-Ser536
      phosphorylation, vascular cell adhesion molecule-1 (VCAM-1) expression, and THP-1
      monocyte adhesion. Ectopic expression of GSK3beta-S9A, a constitutively active
      mutant of GSK3beta, significantly restored complete telmisartan-inhibited NF
      kappaB p65-Ser536 phosphorylation, VCAM-1 expression, and THP-1 monocyte
      adhesion. In addition, it reversed telmisartan-repressed IKKbeta expression.
      Among the ARB, including losartan and fimasartan, only telmisartan increased
      GSK3beta-Ser9 phosphorylation, and telmisartan-induced GSK3beta-Ser9
      phosphorylation remained unchanged by pretreatment with GW9662, a specific and
      irreversible peroxisome proliferator-activated receptor gamma (PPARgamma)
      antagonist. Finally, in the aortas of HFD-fed mice, telmisartan treatment
      significantly attenuated HFD-induced upregulation of NF-kappaB p65-Ser536
      phosphorylation, VCAM-1 expression, and IKKbeta expression and downregulation of
      GSK3beta-Ser9 phosphorylation. Taken together, our findings demonstrated that
      telmisartan ameliorates hyperglycemia-exacerbated vascular inflammation, at least
      in part, by inducing GSK3beta-Ser9 phosphorylation, which consequently inhibits
      IKKbeta expression, NF-kappaB p65-Ser536 phosphorylation, and VCAM-1 expression
      in a PPARgamma-independent manner.

PMID- 28754591
TI  - CaMKII inhibition mitigates ischemia/reperfusion-elicited calpain activation and
      the damage to membrane skeleton proteins in isolated rat hearts.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been implicated in
      myocardial ischemia/reperfusion (IR) injury. The aim of this study was to
      determine the effect of CaMKII on the damage to membrane skeleton proteins, which
      is an important cause of IR injury. Isolated rat hearts were subjected to 45-min
      global ischemia/2-h reperfusion. Both KN-62 and KN-93 were used to inhibit
      CaMKII. Compared with controls, the hearts in the IR group exhibited remarkable
      myocardial injury area, LDH release, cell apoptosis and contractile dysfunction,
      along with an increase in the phosphorylation of CaMKII and its substrate
      phospholamban. Treatment with either KN-62 or KN-93 mitigated both the heart
      injury and the phosphorylation of CaMKII and phospholamban. The analysis of cell
      skeleton proteins revealed that IR injury resulted in an increase in the 150-kDa
      fragments resulting from the degradation of alpha-fodrin and dystrophin
      translocating from the sarcolemmal membrane to the cytosol and a decrease in the
      220-kDa isoform of ankyrin-B. As expected, Evans blue dye staining showed an
      increase in membrane permeability or membrane rupture in the IR group. All of
      these alterations were alleviated by treatment with either KN-62 or KN-93. In
      addition, both KN-62 and KN-93 blocked the activity and membrane recruitment of
      calpain, a key protease responsible for destroying cell skeleton proteins during
      IR injury. In conclusion, our data provide evidence that damage to membrane
      skeleton proteins via calpain is a destructive downstream event of CaMKII
      activation in the setting of myocardial IR injury.

PMID- 28754592
TI  - Plant G-protein beta subunits positively regulate drought tolerance by elevating
      detoxification of ROS.
AB  - Heterotrimeric guanine-nucleotide-binding proteins (G-proteins) consist of alpha,
      beta and gamma subunits and play important roles in response and tolerance to
      abiotic stresses in plants, but the function of the heterotrimeric G-protein beta
      subunit in response to drought remains unclear. In the present study, the AGB1
      mutants (agb1-2-1 and agb1-3-2) were more sensitive to drought than the wild
      type. The overexpression of mulberry (Morus alba L.) G-protein beta subunit in
      transgenic tobacco (Nicotiana tabacum L.) significantly enhanced the plants'
      drought tolerance. The transgenic tobacco plants had higher proline contents and
      peroxidase activities, and lower malonaldehyde and hydrogen peroxide contents and
      superoxide free radical accumulations under drought conditions. Additionally,
      transcript levels of the tobacco antioxidative genes, NtSOD and NtCAT, increased
      in drought-stressed transgenic tobacco plants. Thus, the heterotrimeric G-protein
      beta subunits positively regulate drought tolerance in plants.

PMID- 28754593
TI  - LncRNA-SNHG1 contributes to gastric cancer cell proliferation by regulating
      DNMT1.
AB  - OBJECTIVE: The objective of this study was to determine the expression of long
      chain non-coding RNA SNHG1 (lncRNA-SNHG1) in gastric carcinoma and explore its
      function on cancer cell proliferation. METHODS: The expression of lncRNA-SNHG1 in
      tumor tissues and corresponding adjacent tissues from 50 patients with gastric
      cancer was detected with realtime-PCR. The relationships between the expression
      of lncRNA-SNHG1 and clinicopathological features of gastric cancer patients were
      analyzed. Survival analysis was performed to study the correlation between lncRNA
      SNHG1 expression and patient prognosis. To assess the effect of LncRNA SNHG1 on
      proliferation in cancer cells, cell viability and colony formation assays were
      conducted when lncRNA SNHG1 was upregulated or downregulated by Lentivirus or
      plasmid in gastric cancer cells. Furthermore, in vivo tumor assay was performed
      to confirm the impact of lncRNA SNHG1 on proliferation of gastric cancer.
      RESULTS: The expression of lncRNA SNHG1 in gastric cancer tissues was
      significantly higher than that in adjacent tissues and was correlated with TNM
      stage, T stage, and lymph node metastasis. The survival time of patients with
      higher expression level of lncRNA-SNHG1 was significantly lower than that of the
      lower expression level. LncRNA-SNHG1 accelerated the proliferation of gastric
      cancer cells obviously and increased the expression of DNMT1. CONCLUSION: LncRNA
      SNHG1 promotes DNMT1 expression, which facilitates the gastric cancer
      proliferation.

PMID- 28754594
TI  - MicroRNA-125b-5p modulates the inflammatory state of macrophages via targeting B7
      H4.
AB  - As a newly identified negative costimulatory molecule of B7 family, B7-H4
      suppresses T cell function via inhibiting cell proliferation and cytokine
      secretion. Although B7-H4 mRNA is widely distributed in various tissues, its
      protein expression is strongly limited, suggesting B7-H4 may be regulated post
      transcriptionally. However, the mechanism underlying the inducement of B7-H4
      expression remains unclear. In the present study, we identified specific
      targeting sites for miR-125b-5p in the 3'-UTR of B7-H4 gene, and showed that
      overexpression of miR-125b-5p downregulated B7-H4 expression in macrophages. We
      also demonstrated that in the activated macrophages, B7-H4 expression could be
      significantly induced by dexamethasone treatment post-transcriptionally, and that
      the induction of B7-H4 expression was accomplished by inversely correlated
      alteration of miR-125b-5p level. Additionally, our data showed that the
      inflammatory state of macrophages was enhanced by miR-125b-5p at least partially
      via targeting B7-H4. Taken together, our results demonstrated for the first time
      that miR-125b-5p could regulate the inflammatory state of macrophages via
      directly targeting B7-H4.

PMID- 28754596
TI  - Tonic Signals: Why Do Lymphocytes Bother?
AB  - Since the 1990s it has been known that B and T lymphocytes exhibit low-level,
      constitutive signaling in the basal state (tonic signaling). These lymphocytes
      display a range of affinity for self, which in turn generates a range of tonic
      signaling. Surprisingly, what signaling pathways are active in the basal state
      and the functional relevance of the observed tonic signaling heterogeneity remain
      open questions today. Here we summarize what is known about the mechanistic and
      functional details of tonic signaling. We highlight recent advances that have
      increased our understanding of how the amount of tonic signal impacts immune
      function, describing novel tools that have moved the field forward and toward a
      molecular understanding of tonic signaling.

PMID- 28754597
TI  - Impacts of Longitudinal Mentorship to Strengthen the HIV Workforce: Qualitative
      Evidence of Changes in Clinicians' Knowledge, Attitudes, and Practice.
AB  - The Clinician Scholars Program at the Midwest AIDS Training and Education Center
      strengthens the workforce by increasing knowledge and skills related to HIV
      prevention and care. The 1-year individualized training program for minority
      serving clinicians includes intensive mentoring and networking. Qualitative exit
      interviews (N = 50) conducted over 4 years demonstrate the effectiveness of the
      training, including changes at the individual and systems levels. Findings show
      that almost all graduates reported improvements in knowledge, two-thirds reported
      changes in empathic capacity and cultural competence, and nearly three-quarters
      reported changes in clinical practice. Scholars indicated improvements in
      knowledge and practice of HIV prevention, including pre-exposure prophylaxis and
      managing medications and comorbidities. A third of the Scholars reported
      improvements in their clinical practices related to linking and retaining
      patients in HIV care, which demonstrated positive movement along the HIV care
      continuum, a key focus area of the National HIV AIDS Strategy.

PMID- 28754595
TI  - Mapping the Consequences of Impaired Synaptic Plasticity in Schizophrenia through
      Development: An Integrative Model for Diverse Clinical Features.
AB  - Schizophrenia is associated with alterations in sensory, motor, and cognitive
      functions that emerge before psychosis onset; identifying pathogenic processes
      that can account for this multi-faceted phenotype remains a challenge.
      Accumulating evidence suggests that synaptic plasticity is impaired in
      schizophrenia. Given the role of synaptic plasticity in learning, memory, and
      neural circuit maturation, impaired plasticity may underlie many features of the
      schizophrenia syndrome. Here, we summarize the neurobiology of synaptic
      plasticity, review evidence that plasticity is impaired in schizophrenia, and
      explore a framework in which impaired synaptic plasticity interacts with brain
      maturation to yield the emergence of sensory, motor, cognitive, and psychotic
      features at different times during development in schizophrenia. Key gaps in the
      literature and future directions for testing this framework are discussed.

PMID- 28754598
TI  - ?

PMID- 28754599
TI  - Bioassays to evaluate non-contact spatial repellency, contact irritancy, and
      acute toxicity of permethrin-treated clothing against nymphal Ixodes scapularis
      ticks.
AB  - Summer-weight clothing articles impregnated with permethrin are available as a
      personal protective measure against human-biting ticks in the United States.
      However, very few studies have addressed the impact of contact with summer-weight
      permethrin-treated textiles on tick vigor and behavior. Our aim was to generate
      new knowledge of how permethrin-treated textiles impact nymphal Ixodes scapularis
      ticks, the primary vectors in the eastern United States of the causative agents
      of Lyme disease, human anaplasmosis, and human babesiosis. We developed a series
      of bioassays designed to: (i) clarify whether permethrin-treated textiles impact
      ticks through non-contact spatial repellency or contact irritancy; (ii) evaluate
      the ability of ticks to remain in contact with vertically oriented permethrin
      treated textiles, mimicking contact with treated clothing on arms or legs; and
      (iii) determine the impact of timed exposure to permethrin-treated textiles on
      the ability of ticks to move and orient toward a human finger stimulus, thus
      demonstrating normal behavior. Our results indicate that permethrin-treated
      textiles provide minimal non-contact spatial repellency but strong contact
      irritancy against ticks, manifesting as a "hot-foot" effect and resulting in
      ticks actively dislodging from contact with vertically oriented treated textile.
      Preliminary data suggest that the contact irritancy hot-foot response may be
      weaker for field-collected nymphs as compared with laboratory-reared nymphs
      placed upon permethrin-treated textile. We also demonstrate that contact with
      permethrin-treated textiles negatively impacts the vigor and behavior of nymphal
      ticks for >24h, with outcomes ranging from complete lack of movement to impaired
      movement and unwillingness of ticks displaying normal movement to ascend onto a
      human finger. The protective effect of summer-weight permethrin-treated clothing
      against tick bites merits further study.

PMID- 28754600
TI  - Building blocks for institutional preparation of CTL019 delivery.
AB  - Chimeric antigen receptor (CAR) T-cell therapy is an investigational
      immunocellular therapy that reprograms a patient's cytotoxic T cells to engage
      and eliminate malignant cells. CAR T-cell therapies targeting the CD19 antigen
      have demonstrated high efficacy in clinical trials for patients with B-cell
      malignancies and may potentially be available on a broader scale in the future.
      CAR T-cell therapy begins with the collection of a sufficient number of T cells
      from a patient's peripheral blood through leukapheresis. Several factors must be
      considered when patients undergo leukapheresis for CAR T-cell therapy, including
      age and prior therapies. The leukapheresis material is shipped to a manufacturing
      facility, followed by return of the CAR T cells to the treatment center. Careful
      coordination of a multidisciplinary team composed of physicians, nurses,
      pharmacists and other hospital personnel is critical for the proper care of the
      patient before, during and after CAR T-cell therapy. CAR T-cell therapy has been
      associated with adverse events (AEs) such as cytokine release syndrome, which
      requires rapid attention by the emergency department, intensive care unit and
      hospital pharmacy. In this review, we discuss several aspects of institutional
      preparation for leukapheresis, CAR T-cell infusion and AE management based on our
      experience with clinical trials of the CD19 CAR T-cell therapy CTL019.

PMID- 28754601
TI  - Magnesium sulfate infusion for acute asthma in the emergency department.
AB  - OBJECTIVES: To describe the role of intravenous magnesium sulfate (MgSO4) as
      therapy for acute severe asthma in the pediatric emergency department (ED).
      SOURCE: Publications were searched in the PubMed and Cochrane databases using the
      following keywords: magnesium AND asthma AND children AND clinical trial. A total
      of 53 publications were retrieved using this criteria. References of relevant
      articles were also screened. The authors included the summary of relevant
      publications where intravenous magnesium sulfate was studied in children (age <18
      years) with acute asthma. The NAEPP and Global Initiative for Asthma expert panel
      guidelines were also reviewed. SUMMARY OF THE DATA: There is a large variability
      in the ED practices on the intravenous administration of MgSO4 for severe asthma.
      The pharmacokinetics of MgSO4 is often not taken into account with a consequent
      impact in its pharmacodynamics properties. The cumulative evidence points to the
      effectiveness of intravenous MgSO4 in preventing hospitalization, if utilized in
      a timely manner and at an appropriate dosage (50-75mg/kg). For every five
      children treated in the ED, one hospital admission could be prevented. Another
      administration modality is a high-dose continuous magnesium sulfate infusion
      (HDMI) as 50mg/kg/h/4h (200mg/kg/4h). The early utilization of HDMI for non
      infectious mediated asthma may be superior to a MgSO4 bolus in avoiding
      admissions and expediting discharges from the ED. HDMI appears to be cost
      effective if applied early to a selected population. Intravenous MgSO4 has a
      similar safety profile than other asthma therapies. CONCLUSIONS: Treatment with
      intravenous MgSO4 reduces the odds of hospital admissions. The use of intravenous
      MgSO4 in the emergency room was not associated with significant side effects or
      harm. The authors emphasize the role of MgSO4 as an adjunctive therapy, while
      corticosteroids and beta agonist remain the primary acute therapeutic agents.

PMID- 28754602
TI  - Adolescents' physical activity is associated with previous and current physical
      activity practice by their parents.
AB  - OBJECTIVE: The purpose of this study was to determine whether parents' current
      and previous physical activity practice is associated with adolescents' physical
      activity. METHODS: The sample was composed of 1231 adolescents (14-17 years), and
      1202 mothers and 871 fathers were interviewed. Weight and height of the
      adolescents were measured. Self-reported parents' weight and height were
      obtained. The current and previous physical activity levels (Baecke's
      questionnaire) of parents (during childhood and adolescence) and adolescents'
      physical activity levels were obtained using a questionnaire. The magnitude of
      the associations between parent and adolescent physical activity levels was
      determined by binary logistic regression (adjusted by sex, age, and socioeconomic
      level of adolescents and education level of parents). RESULTS: The current
      physical activity practice by parents was associated with adolescents' physical
      activity (p<0.001). The physical activities reported by parents in their
      childhood and adolescence were also associated with higher physical activity
      levels among adolescents. Adolescents whose parents were both physically active
      in the past and present were six times (OR=6.67 [CI=1.94-22.79]) more likely to
      be physically active compared to adolescents with no parents who were physically
      active in the past. CONCLUSIONS: The current and previous physical activities of
      parents were associated with higher levels of physical activity in adolescents,
      even after controlling for confounding factors.

PMID- 28754604
TI  - Regulation of fetal male germ cell development by members of the TGFbeta
      superfamily.
AB  - There is now substantial evidence that members of the transforming growth factor
      beta (TGFbeta family) regulate germ cell development in the mouse fetal testis.
      Correct development of germ cells during fetal life is critical for establishment
      of effective spermatogenesis and for avoiding the formation of testicular germ
      cell cancer in later life. Here we consider the evidence for involvement of
      various TGFbeta family members, attempt to reconcile discrepancies and clarify
      what we believe to be the likely in vivo roles of these factors.

PMID- 28754603
TI  - A pilgrim's progress: Seeking meaning in primordial germ cell migration.
AB  - Comparative studies of primordial germ cell (PGC) development across organisms in
      many phyla reveal surprising diversity in the route of migration, timing and
      underlying molecular mechanisms, suggesting that the process of migration itself
      is conserved. However, beyond the perfunctory transport of cellular precursors to
      their later arising home of the gonads, does PGC migration serve a function? Here
      we propose that the process of migration plays an additional role in quality
      control, by eliminating PGCs incapable of completing migration as well as through
      mechanisms that favor PGCs capable of responding appropriately to migration cues.
      Focusing on PGCs in mice, we explore evidence for a selective capacity of
      migration, considering the tandem regulation of proliferation and migration, cell
      intrinsic and extrinsic control, the potential for tumors derived from failed PGC
      migrants, the potential mechanisms by which migratory PGCs vary in their cellular
      behaviors, and corresponding effects on development. We discuss the implications
      of a selective role of PGC migration for in vitro gametogenesis.

PMID- 28754605
TI  - Train hard, sleep well? Perceived training load, sleep quantity and sleep stage
      distribution in elite level athletes.
AB  - OBJECTIVES: Sleep is essential for recovery and performance in elite athletes.
      While it is generally assumed that exercise benefits sleep, high training load
      may jeopardize sleep and hence limit adequate recovery. To examine this, the
      current study assessed objective sleep quantity and sleep stage distributions in
      elite athletes and calculated their association with perceived training load.
      DESIGN: Mixed-methods. METHODS: Perceived training load, actigraphy and one
      channel EEG recordings were collected among 98 elite athletes during 7
      consecutive days of regular training. RESULTS: Actigraphy revealed total sleep
      durations of 7:50+/-1:08h, sleep onset latencies of 13+/-15min, wake after sleep
      onset of 33+/-17min and sleep efficiencies of 88+/-5%. Distribution of sleep
      stages indicated 51+/-9% light sleep, 21+/-8% deep sleep, and 27+/-7% REM sleep.
      On average, perceived training load was 5.40+/-2.50 (scale 1-10), showing large
      daily variability. Mixed-effects models revealed no alteration in sleep quantity
      or sleep stage distributions as a function of day-to-day variation in preceding
      training load (all p's>.05). CONCLUSIONS: Results indicate healthy sleep
      durations, but elevated wake after sleep onset, suggesting a potential need for
      sleep optimization. Large proportions of deep sleep potentially reflect an
      elevated recovery need. With sleep quantity and sleep stage distributions
      remaining irresponsive to variations in perceived training load, it is
      questionable whether athletes' current sleep provides sufficient recovery after
      strenuous exercise.

PMID- 28754606
TI  - Prolonged running increases knee moments in sidestepping and cutting manoeuvres
      in sport.
AB  - OBJECTIVES: To investigate how knee kinematics, kinetics and loading changes
      during sidestepping tasks following a prolonged running protocol performed in a
      laboratory setting. DESIGN: All participants performed sidestepping, and
      crossover cutting tasks in a randomised order before and after a 60min running
      protocol on a non-motorised treadmill that simulated an AF game. METHODS: Eight
      healthy male participants who partook in semi-professional and amateur Australian
      Football undertook a series of straight line runs, sidestepping (SS), and
      crossover cutting (XO) tasks before and after a simulated game of Australian
      football. Kinematic data were analysed at initial foot contact of the SS and XO
      manoeuvres and kinetic data were analysed during the weight acceptance phase of
      the stance. RESULTS: The knee was significantly more flexed at foot contact
      following fatigue compared to pre-fatigue states. Fatigue was also a factor
      contributing to significant increases in internal knee extension moments.
      Significant differences were also observed between SS and XO trials with
      flexion/extension moments, with notable differences in varus/valgus and
      internal/external rotation moments. CONCLUSIONS: Acute angles of knee flexion at
      foot strike in a fatigued state may place the joint at an increased risk of
      injury. Increases in knee extension moments in the fatigued state suggests the
      knee joint must withstand significantly high stresses once fatigued.

PMID- 28754607
TI  - Reversal of nocturnal non-dipping of blood pressure after Levothyroxine therapy
      in patients with subclinical hypothyroidism.
AB  - AIMS: To study the loss of diurnal variation in blood pressure in normotensive
      patients with Subclinical/overt hypothyroidism and effect of Levothyroxine (L-T4)
      treatment. MATERIALS AND METHODS: In this interventional study Eighty patients
      between 17- 50 years with newly detected OH and SCH (74 women and 6 men) and nine
      euthyroid subjects (all men) with blood pressure <140/90 were recruited. All
      patients underwent 24h ambulatory blood pressure monitoring (ABPM) using ABPM
      machine before and after treatment with L-T4. Diurnal index (DI), Percent time
      elevation (PTE), Hyperbaric impact (HBI) were studied pre and post L-T4
      treatment. RESULTS: Of the 89 subjects (22 SCH, 58 OH and 9 controls), 7 of the
      SCH and 30 of OH subjects reported back in follow up after L-T4 supplementation
      for evaluation. DI, HBI and PTE when compared at baseline between different
      groups (SCH- OH, SCH- control, OH- control) were insignificant. After L-T4
      supplementation DI, HBI and PTE varied significantly with p value 0.007, 0.003
      and 0.003 respectively between SCH- OH only. Post L-T4 analysis in SCH group was
      statistically insignificant (p-value 0.102) but a trend toward improvement in DI
      was noted (baseline and post treatment DI mean 7.00 and 13.00 respectively).
      CONCLUSION: Loss of nocturnal dipping was found in patients with OH and SCH which
      was restored after L-T4 therapy only in patients with SCH and not with OH.
      TREATMENT: of SCH patients with high cardiovascular risk may be beneficial in
      this setting and can be a new indication for LT4 therapy in SCH.

PMID- 28754608
TI  - Inflammatory mediators mediate airway smooth muscle contraction through a G
      protein-coupled receptor-transmembrane protein 16A-voltage-dependent Ca2+ channel
      axis and contribute to bronchial hyperresponsiveness in asthma.
AB  - BACKGROUND: Allergic inflammation has long been implicated in asthmatic
      hyperresponsiveness of airway smooth muscle (ASM), but its underlying mechanism
      remains incompletely understood. Serving as G protein-coupled receptor agonists,
      several inflammatory mediators can induce membrane depolarization, contract ASM,
      and augment cholinergic contractile response. We hypothesized that the signal
      cascade integrating on membrane depolarization by the mediators might involve
      asthmatic hyperresponsiveness. OBJECTIVE: We sought to investigate the signaling
      transduction of inflammatory mediators in ASM contraction and assess its
      contribution in the genesis of hyperresponsiveness. METHODS: We assessed the
      capacity of inflammatory mediators to induce depolarization currents by
      electrophysiological analysis. We analyzed the phenotypes of transmembrane
      protein 16A (TMEM16A) knockout mice, applied pharmacological reagents, and
      measured the Ca2+ signal during ASM contraction. To study the role of the
      depolarization signaling in asthmatic hyperresponsiveness, we measured the
      synergistic contraction by methacholine and inflammatory mediators both ex vivo
      and in an ovalbumin-induced mouse model. RESULTS: Inflammatory mediators, such as
      5-hydroxytryptamin, histamine, U46619, and leukotriene D4, are capable of
      inducing Ca2+-activated Cl- currents in ASM cells, and these currents are
      mediated by TMEM16A. A combination of multiple analysis revealed that a G protein
      coupled receptor-TMEM16A-voltage-dependent Ca2+ channel signaling axis was
      required for ASM contraction induced by inflammatory mediators. Block of TMEM16A
      activity may significantly inhibit the synergistic contraction of acetylcholine
      and the mediators and hence reduces hypersensitivity. CONCLUSIONS: A G protein
      coupled receptor-TMEM16A-voltage-dependent Ca2+ channel axis contributes to
      inflammatory mediator-induced ASM contraction and synergistically activated
      TMEM16A by allergic inflammatory mediators with cholinergic stimuli.

PMID- 28754609
TI  - The drug delivery field at the inflection point: Time to fight its way out of the
      egg.
AB  - The world is becoming a better place, in part, by breakthrough findings by
      scientists. In the drug delivery field, many breakthrough formulations have been
      achieved helping patients deal with various diseases effectively. The recent
      progress, however, has been slowing down, and many important drug delivery
      problems have not been resolved. They can be overcome by understanding the causes
      and finding the remedies. For the last three decades, the field has been
      overwhelmed by nanotechnology, nanomedicine, and many nano-sized drug delivery
      systems. Disappointing outcomes of nano-sized formulations (nanoformulations) in
      clinical studies indicate that our overall approach of nanomedicine needs serious
      reevaluation. The limited advantages of nanoformulations were drastically
      exaggerated, and the assumptions used in nanomedicine and nanoformulations turned
      out to be inapplicable to clinical applications. The drug delivery field is at
      the strategic inflection point, and we all have to face the reality by absorbing
      the inconvenient truth and fight our way out of the egg to break the ill
      conceived illusion of nanomedicine. Scientists are proud of their independent
      thinking and their work that can change the world, but the current climate does
      not allow them to be true scientists. The future of the drug delivery field
      depends on how effectively we can find talented young scientists with motivation,
      cultivate them with resources, provide them with an environment for the free
      exchange of ideas, and nurture them with purpose, passion, and the conviction of
      doing meaningful science.

PMID- 28754610
TI  - Secretory phospholipase A2 responsive liposomes exhibit a potent anti-neoplastic
      effect in vitro, but induce unforeseen severe toxicity in vivo.
AB  - The clinical use of liposomal drug delivery vehicles is often hindered by
      insufficient drug release. Here we present the rational design of liposomes
      optimized for secretory phospholipase A2 (sPLA2) triggered drug release, and test
      their utility in vitro and in vivo. We hypothesized that by adjusting the level
      of cholesterol in anionic, unsaturated liposomes we could tune the enzyme
      specificity based on membrane fluidity, thus obtaining liposomes with an improved
      therapeutic outcome and reduced side effects. Cholesterol is generally important
      as a component in the membranes of liposome drug delivery systems due to its
      stabilizing effects in vivo. The incorporation of cholesterol in sPLA2 sensitive
      liposomes has not previously been possible due to reduced sPLA2 activity.
      However, in the present work we solved this challenge by optimizing membrane
      fluidity. In vitro release studies revealed enzyme specific drug release.
      Treatment of two different cancer cell lines with liposomal oxaliplatin revealed
      efficient growth inhibition compared to that of clinically used stealth
      liposomes. The in vivo therapeutic effect was evaluated in nude NMRI mice using
      the sPLA2 secreting mammary carcinoma cell line MT-3. Three days after first
      treatment all mice having received the novel sPLA2 sensitive liposome formulation
      were euthanized due to severe systemic toxicity. Thus the present study
      demonstrates that great caution should be implemented when utilizing sPLA2
      sensitive liposomes and that the real utility can only be disclosed in vivo. The
      present studies have clinical implications, as sPLA2 sensitive formulations are
      currently undergoing clinical trials (LiPlaCis(r)).

PMID- 28754611
TI  - Transdermal delivery of gentamicin using dissolving microneedle arrays for
      potential treatment of neonatal sepsis.
AB  - Neonatal infections are a leading cause of childhood mortality in low-resource
      settings. World Health Organization guidelines for outpatient treatment of
      possible serious bacterial infection (PSBI) in neonates and young infants when
      referral for hospital treatment is not feasible include intramuscular gentamicin
      (GEN) and oral amoxicillin. GEN is supplied as an aqueous solution of gentamicin
      sulphate in vials or ampoules and requires health care workers to be trained in
      dose calculation or selection of an appropriate dose based on the patient's
      weight band and to have access to safe injection supplies and appropriate sharps
      disposal. A simplified formulation, packaging, and delivery method to treat PSBI
      in low-resource settings could decrease user error and expand access to
      lifesaving outpatient antibiotic treatment for infants with severe infection
      during the neonatal period. We developed dissolving polymeric microneedles (MN)
      arrays to deliver GEN transdermally. MN arrays were produced from aqueous blends
      containing 30% (w/w) of GEN and two polymers approved by the US Food and Drug
      Administration: sodium hyaluronate and poly(vinylpyrrolidone). The arrays (19*19
      needles and 500MUm height) were mechanically strong and were able to penetrate a
      skin simulant to a depth of 378MUm. The MN arrays were tested in vitro using a
      Franz Cell setup delivering approximately 4.45mg of GEN over 6h. Finally, three
      different doses (low, medium, and high) of GEN delivered by MN arrays were tested
      in an animal model. Maximum plasma levels of GEN were dose-dependent and ranged
      between 2 and 5MUg/mL. The time required to reach these levels post-MN array
      application ranged between 1 and 6h. This work demonstrated the potential of
      dissolving MN arrays to deliver GEN transdermally at therapeutic levels in vivo.

PMID- 28754612
TI  - Differentiation potential of human CD133 positive hematopoietic stem cells into
      motor neuron- like cells, in vitro.
AB  - Spinal cord injuries and motor neuron-related disorders impact on life of many
      patients around the world. Since pharmacotherapy and surgical approaches were not
      efficient to regenerate these types of defects; stem cell therapy as a good
      strategy to restore the lost cells has become the focus of interest among the
      scientists. Umbilical cord blood CD133+ hematopoietic stem cells (UCB- CD133+
      HSCs) with self- renewal property and neural lineage differentiation capacity are
      ethically approved cell candidate for use in regenerative medicine. In this
      regard the aim of this study was to quantitatively evaluate the capability of
      these cells to differentiate into motor neuron-like cells (MNL), in vitro. CD133+
      HSCs were isolated from human UCB using MACS system. After cell characterization
      using flow cytometry, the cells were treated with a combination of Retinoic acid,
      Sonic hedgehog, Brain derived neurotrophic factor, and B27 through a 2- step
      procedure for two weeks. The expression of MN-specific markers was examined using
      qRT- PCR, flow cytometry and immunocytochemistry. By the end of the two-week
      differentiation protocol, CD133+ cells acquired unipolar MNL morphology with thin
      and long neurites. The expression of Isl-1(62.15%), AChE (41.83%), SMI-32
      (21.55%) and Nestin (17.46%) was detected using flow cytometry and
      immunocytochemistry. The analysis of the expression of PAX6, ISL-1, ACHE, CHAT
      and SMI-32 revealed that MNLs present these neural markers at levels comparable
      with undifferentiated cells. In Conclusion Human UCB- CD133+ HSCs are remarkably
      potent cell candidates to transdifferentiate into motor neuron-like cells, in
      vitro.

PMID- 28754613
TI  - Growth performance, innate immune responses and disease resistance of fingerling
      blunt snout bream, Megalobrama amblycephala adapted to different berberine
      dietary feeding modes.
AB  - A 8-week feeding trial was conducted to evaluate the effect of different
      berberine-dietary feeding modes on growth, non-specific immune responses and
      disease resistance of blunt snout bream, Megalobrama amblycephala. Fish (average
      initial weight 4.70 +/- 0.02 g) were fed two fat levels (5% and 10%) diets in
      three berberine-feeding modes (supplementing 50 mg/kg berberine continuously, two
      week or four-week intervals) with four replicates, respectively. Then, fish were
      challenged by Aeromonas hydrophila and mortality was recorded for the next 96 h
      after feeding trial. The results showed that different feeding modes of berberine
      significantly influenced growth, innate immunity and antioxidant capability of
      fish. Fish fed normal diet with 50 mg/kg berberine at two-week interval mode
      reflected remarkably (P < 0.05) high weight gain (WG). Plasma TC and TG contents
      were significantly (P < 0.05) decreased. The lysozyme (LYZ) activities,
      complement component 3 (C3) and complement component 4 (C4) concentrations were
      significantly (P < 0.05) increased. Fish not only exhibited relatively low
      hepatopancreas malondialdehyde (MDA) and lipid peroxide (LPO) contents, but also
      significantly (P < 0.05) improved superoxide dismutase (SOD) and catalase (CAT)
      activities. Fish mortality after challenged by Aeromonas hydrophila was
      decreased. Same results were also presented in fish fed high-fat diet with 50
      mg/kg berberine at two-week, four-week intervals or continuous feeding modes.
      Based on fish healthy improvement and feeding cost saving, blunt snout bream fed
      normal diet with 50 mg/kg berberine at two-week interval or fed high-fat diet
      with berberine at two-week or four-week intervals were optimal feeding mode,
      respectively.

PMID- 28754614
TI  - Inspiring surgeons of the future: A school outreach event and possible solution
      to the imminent recruitment crisis.

PMID- 28754615
TI  - Role of transforming growth factor-beta1 in triple negative breast cancer
      patients.
AB  - BACKGROUND: We aimed to demonstrate the prognostic value of TGF-beta1 in triple
      negative breast cancer (TNBC) and its association with clinicopathological
      characteristics of TNBC. MATERIALS AND METHODS: A total of 180 women were
      randomly selected from non-metastatic invasive TNBC patients diagnosed at two
      hospitals between 2003 and 2012. Lmmunohistochemistry was performed to semi
      quantify the expression of TGF-beta1. Relationship between TGF-beta1 expression
      and clinicopathological features was performed by Chi-square test. Univariate and
      multivariate survival analyses were performed to identify the prognostic role of
      TGF-beta1 expression on survival outcomes. RESULTS: Of the 180 women included in
      this study, 67 (37.2%) patients expressed high level of TGF-beta1. High
      expression of cytoplasmic TGF-beta1 was correlated with higher histologic tumor
      grade (P < 0.001) and lymph node status (P < 0.001), and more axillary lymph node
      dissection (P = 0.029). High cytoplasmic TGF-beta1 expression was associated with
      reduced disease-free survival (DFS) and overall survival (OS) by log-rank test
      (PDFS<0.001, POS = 0.045). However, multivariate survival analyses showed that
      high TGF-beta1 was marginally correlated with unfavorable DFS (hazard ratio (HR)
      1.796, 95% CI 0.995-3.242, P = 0.052), while it was not significantly associated
      with OS (HR 0.747, 95% CI 0.367-1.522, P = 0.422). CONCLUSIONS: This multi
      centered retrospective study highlights the high expression of cytoplasmic TGF
      beta1 in TNBC is associated with higher histologic grade and lymph node status,
      more axillary lymph node dissection, as well as reduced DFS. Our observation that
      the prognostic role of TGF-beta1 in TNBC suggests potential rationale for using
      therapeutic strategies based on targeting TGF-beta1 in advanced tumors.

PMID- 28754616
TI  - Role of uremic toxin indoxyl sulfate in the progression of cardiovascular
      disease.
AB  - The prevalence of cardiovascular disease (CVD) among patients with chronic kidney
      disease (CKD) is relatively high. Deterioration of renal function in CKD leads to
      accumulation of indoxyl sulfate, a tryptophan metabolite produced by gut
      microbiota. It is acknowledged that indoxyl sulfate is capable to stimulate
      oxidative stress, which in turn contributes to the progression of vascular
      disorders and its resultant coronary artery disease. Recent research have
      demonstrated the adverse effects of indoxyl sulfate on the heart, together with
      the acceleration of vascular dysfunction, suggesting that indoxyl sulfate might
      contribute to high prevalence of CVD in CKD. The present mini review has focused
      on the potential mechanisms by which indoxyl sulfate exerts this pro-oxidant
      effects on the cardiovascular system. The action of indoxyl sulfate are related
      to multiple NADPH oxidase-mediated redox signaling pathways, which have been
      implicated in the pathophysiology of different forms of CVD, including chronic
      heart failure, arrhythmia, atherosclerotic vascular disease and coronary
      calcification. Future therapeutic options are discussed, including modulating gut
      microbial flora and blocking responsible pathophysiologic pathways.

PMID- 28754617
TI  - Infection by Schistosoma mansoni during pregnancy: Effects on offspring immunity.
AB  - About 25 million Brazilians live in areas at risk of contracting the disease
      caused by the trematoda Schistosoma mansoni, the schistosomiasis mansoni.
      Although the adult parasites inhabit the blood vessels, probably the main element
      responsible for the pathology of the disease are the eggs, whose deposition in
      the liver results in formation of granulomas and hypersensitivity mediated by CD4
      T cells. In the course of infection, the profile of T helper 1 (Th1) and Th2
      cytokines released by immune cells is correlated with the extent of inflammation
      in the granuloma and with the disease severity. While a Th1 immune response
      favors the local inflammation and the disease progression, the Th2 immune
      response has protective character. Also during pregnancy, it is essential a fine
      adjustment of a Th1/Th2 in the maternal-fetal interface, which ensures the
      pregnancy progress with peculiar immune characteristics. In particular, the
      maternal exposure to antigens has been associated with their presence in fetal
      circulation. The exposure to intrauterine antigens can imply an immune tolerance
      of the fetus to such components. In turn, the transfer of antigens and antibodies
      from mother to offspring during breastfeeding is an important stage of maturation
      and capacitation of immune offspring in future infections against pathogens. This
      review aims to gather bibliographic data to assist in the understanding of
      immunological features printed on offspring of mothers infected with S. mansoni,
      which affect latter immune responses to related or unrelated antigens.

PMID- 28754618
TI  - Hepatoprotective effect of hesperidin in hepatocellular carcinoma: Involvement of
      Wnt signaling pathways.
AB  - AIMS: Wnt3a and Wnt5a are ligands orchestrating the canonical and non-canonical
      pathways, respectively, with involvement in hepatocellular carcinoma (HCC).
      Hesperidin (HP) is a natural product found in citrus fruits and reputed for its
      antitumor activity. The present study aims to investigate the potential
      hepatoprotective effect of HP against thioacetamide (TAA)-induced HCC focusing on
      its potential role on Wnt3a and Wnt5a signaling pathways. MAIN METHODS: Forty
      rats were equally divided into groups; normal control, HP control (receiving HP,
      150mg/kg/day), HCC (receiving TAA, 200mg/kg twice weekly for 14weeks) and HP-HCC
      (receiving HP and TAA). Gene expressions of Wnt3a, Wnt5a, beta-catenin and Cyclin
      D1 were assessed by qPCR, while their protein levels, along with active caspase-3
      level, were quantified by ELISA and immunohistochemistry. Liver functions,
      oxidative stress parameters and myeloperoxidase activity were measured. MTT assay
      of hepG2 cells treated with recombinant Wnt3a (10ng/ml) in presence or absence of
      HP (100MUM) was performed. KEY FINDINGS: HCC group exhibited a significant
      increase in Wnt3a, beta-catenin, Cyclin D1 and Wnt5a gene expressions, as well
      as, their protein levels. HP significantly prevented TAA-activated Wnt3a/beta
      catenin and Wnt5a pathways. Moreover, HP exerted hepatoprotective effect by
      significantly improving the oxidative imbalance, inflammation and liver function
      parameters, serum ALT, AST activities, and albumin level. SIGNIFICANCE: Our study
      is the first to report the possible role of Wnt3a/beta-catenin and Wnt5a pathways
      in TAA-induced early HCC model in rats. HP has a prophylactic effect against
      hepatocarcinogenesis via preventing the induction of both canonical and non
      canonical Wnt pathways.

PMID- 28754619
TI  - Celecoxib-induced inhibition of neurogenesis in fetal frontal cortex is
      attenuated by curcumin via Wnt/beta-catenin pathway.
AB  - Celecoxib is widely used in pregnant women but its influence on fetal brain
      neurogenesis is largely unknown. The objective of the present study was to
      examine the influence of celecoxib to fetal brain development and to investigate
      whether curcumin could ameliorate celecoxib-induced neurotoxicity. Pregnant mice,
      cultured neurons and cultured neural progenitor cells were all treated with
      celecoxib with or without curcumin. The change in proliferation, differentiation
      and the activity of Wnt/beta-catenin signaling pathway were then assessed. Here,
      we report that prenatal celecoxib exposure inhibited the activity of Wnt/beta
      catenin pathway and disrupted the proliferation of neuronal progenitor cells,
      leading to a decrease of newborn neurons in fetal frontal cortex. Treatment with
      curcumin significantly could attenuate the celecoxib-induced deficits in
      proliferation through activating the Wnt/beta-Catenin pathway. Our study for the
      first time showed that maternal celecoxib administration caused detrimental
      effects to fetal brain development and provided an evidence of the therapeutic
      role of curcumin in celecoxib-induced neurotoxicity.

PMID- 28754620
TI  - Morphological and thermal studies of chitin-curcumin blends derived
      polyurethanes.
AB  - The present study describes a novel ecofriendly series of chitin/curcumin/1,4
      butane diol (BDO) blend derived polyurethanes (PUs), using hydroxy terminated
      polybutadiene (HTPB) and hexamethylene diisocyanate (HDI) along with different
      mole ratio of chitin, curcumin and BDO. The structural and morphological
      elucidation of the prepared films was done by FTIR and SEM techniques. The
      swelling behavior of the films was analyzed in both water and DMSO, which showed
      that incorporation of chitin increases the hydrophobicity and decreases the rate
      of swelling. Thermal analysis of synthesized PU blends revealed better thermal
      stability with following mole ratio 1:0.5:0.5 of chitin: curcumin: BDO as
      determined by TGA and DSC techniques.

PMID- 28754621
TI  - Effect of extraction procedures on structural, thermal and antioxidant properties
      of ulvan from Ulva lactuca collected in Monastir coast.
AB  - The present work aims to evaluate the effect of an acid extraction as well as a
      combined enzymatic-chemical extraction on structural, thermal and antioxidant
      properties of the sulphated polysaccharide 'ulvan' from the green seaweed Ulva
      lactuca. Structural characterization by FTIR and NMR spectroscopies showed the
      typical peaks of ulvan, namely, uronic acids, rhamnose and sulphate. FTIR
      analysis revealed that the extraction procedures were able to maintain ulvan
      structure. Despite differences in the extraction procedures, 13C NMR spectra were
      globally similar, proving a comparable chemical structure of ulvans. A major
      difference has been observed in signal intensity which reflected the resonance of
      glucose or xylose. Thermal characterization proved that ulvans were thermally
      stable until approximately 180 degrees C. Antioxidant properties of ulvans were
      evaluated in vitro through different antioxidant assays. Ulvan, which is
      extracted at pH 1.5 and 90 degrees C, exhibited the greatest scavenging activity
      (IC50=13.56MUg/ml) towards DPPH radical. Result indicated that Mw has influenced
      inhibitory effect on DPPH radical of ulvan. The current study revealed also a
      high correlation between sulphate contents of ulvans and their reducing power
      (R2=-0.89) and their metal scavenging activity (R2=0.97). Overall, ulvans have
      peculiar structural, thermal and antioxidant properties which promote their use
      in food or pharmaceutical products as natural ingredient.

PMID- 28754622
TI  - Identification and characterization of two germin-like proteins with oxalate
      oxidase activity from Calotropis procera latex.
AB  - Germin-like proteins (GLPs) have been identified in several plant tissues.
      However, only one work describes GLP in latex fluids. Therefore, the goal of this
      study was to investigate GLPs in latex and get new insights concerning the
      structural and functional aspects of these proteins. Two complete sequences with
      high identity (>50%) with other GLPs, termed CpGLP1 and CpGLP2, were obtained and
      consecutively presented 216 and 206 amino acid residues, corresponding to
      molecular masses of 22.7 and 21.7kDa, pI 6.8 and 6.5. The three-dimensional
      models revealed overall folding similar to those reported for other plant GLPs.
      Both deduced sequences were grouped into the GER 2 subfamily. Molecular docking
      studies indicated a putative binding site consisting of three highly conserved
      histidines and a glutamate residue, which interacted with oxalate. This
      interaction was later supported by enzymatic assays. Superoxide dismutase (common
      activity in GLPs) was not detected for CpGLP1 and CpGLP2 by zymogram. The two
      proteins were detected in the latex, but not in non-germinated or germinated
      seeds and calli. These results give additional support that germin-like proteins
      are broadly distributed in plants and they are tissue-specific. This
      particularity deserves further studies to better understand their functions in
      latex.

PMID- 28754623
TI  - Structural re-arrangement of depolymerized sodium alginate enriches peltate
      glandular trichomes and essential oil production of spearmint.
AB  - Over the past decade, radiation-degraded polysaccharides have been used as
      regulators of growth and development in several crop plants. In quest of the
      possible reasons of previously established growth-promotion activity of
      irradiated sodium alginate (ISA), structural parameters of irradiated and un
      irradiated sodium alginate were analysed using Ultraviolet-visible spectroscopy
      (UV-vis) and Fourier Transform Infrared spectroscopic (FT-IR) studies to develop
      an understanding of structure-property relationship. Using foliar application,
      response to graded concentrations of ISA was tested in terms of yield and quality
      attributes of spearmint (Mentha spicata L.). Among different concentrations of
      ISA [0 (control), 40, 80, 120 and 160mgL-1], 80mgL-1 proved to be the optimum
      foliar-spray treatment for most of the parameters studied including peltate
      glandular-trichomes density, which was increased from 20 to 44mm-2. Measurements
      made at 150days after planting revealed that foliar application of ISA at 80mgL-1
      increased the content and yield of spearmint essential oil (EO) by 36.0 and
      122.6%, respectively, in comparison to the control. Compared to the control, gas
      chromatography mass spectrometry (GC-MS) analysis revealed an increase of 18.7%
      in the carvone content and a decrease of 15.7% in limonene content of the
      spearmint EO.

PMID- 28754624
TI  - Dynamics of dimeric kinesins: Limping, effect of longitudinal force, effects of
      neck linker extension and mutation, and comparison between kinesin-1 and kinesin
      2.
AB  - Conventional kinesin (kinesin-1) can walk on microtubule filaments in an
      asymmetric hand-over-hand manner, exhibiting a marked alternation in the mean
      dwell time in successive steps. Here, we study computationally the asymmetric
      stepping dynamics of the kinesin-1 homodimer, revealing its origin and providing
      quantitative explanations of the available experimental data. The alternation in
      the mean dwell time in successive steps arises from the alternation in the
      mechanochemical coupling ratio, which is in turn caused by the alternation in the
      slight variation of the stretched neck linker length. Both the vertical and
      backward longitudinal forces can enhance the asymmetric ratio. Additionally,
      other aspects of the stepping dynamics of the dimer such as the velocity versus
      longitudinal force, extended neck linker, etc., are also studied. In particular,
      the conflicting experimental data, with some showing that the velocity does not
      change with the forward longitudinal load while others showing that the velocity
      increases largely with the forward longitudinal load, are explained
      quantitatively and consistently. The intriguing experimental data showing that
      cysteine-light Drosophila and human kinesin-1 mutants have different load
      dependent velocity from the wild-type cases as well as that kinesin-2 dimers have
      different load-dependent velocity from the kinesin-1 are also explained
      consistently and quantitatively.

PMID- 28754625
TI  - The structure property and endothelial protective activity of fucoidan from
      Laminaria japonica.
AB  - Four antithrombotic fucoidan fractions F1, F2, LF1, and LF2 with different
      monosaccharide composition, molecular weight, and degree of sulfation and sulfate
      position were prepared from Laminaria japonica by hot water extraction and
      radical degradation. Their endothelial protective activity and possible action
      mechanism were studied using both cell- and rat-based models systematically. By
      comparison, the low molecular weight (LMW) fucoidan LF1 and LF2 were more potent
      than the medium molecular weight (MMW) fucoidan F1 and F2 in endothelial
      protection, down-regulation of von Willebrand Factor, CD31 and CD51 expressing
      endothelial microparticles in adrenalin-induced arterial endothelial injury rats
      and human umbilical vein endothelial cell system. However, the highly sulfated
      fucoidan fractions F2 and LF2 were better at inducing FGFR1c-expressing BaF3 cell
      proliferation in the presence of FGF-1, -2, -7, -8, -9 or -10. These results
      indicated that the chemical property of fucoidan was correlated to its specific
      biological activity tested. Therefore, defying fucoidan's monosaccharide
      composition, molecular weight, and degree of sulfation might be important in
      developing it into a medicine.

PMID- 28754626
TI  - In-sights into the effect of heavy metal stress on the endogenous mustard
      cystatin.
AB  - Phytocystatins have been ascribed several protective roles against abiotic and
      biotic stress conditions. It was, therefore, thought worthwhile to document the
      effect of heavy metal stress on the endogenous plant cystatin. The mustard
      cystatin, purified from Brassica juncea (B. juncea) seeds retained its functional
      property of cysteine proteinase inhibition, despite exposure to high
      concentrations of metal ions, Cd2+ and Ni2+. An increase in inhibitory activity,
      ~26% for Ni2+ and ~16% for Cd2+ was observed, suggesting changes in protein
      conformation upon metal ion interaction. Isothermal calorimetric (ITC) studies
      show formation of a 1:1 binary complex on interaction with both metal ions but
      suggest a higher affinity for Ni2+. Fluorescence quenching data suggest a static
      quenching mechanism of interaction. Various spectroscopic analyses, namely,
      synchronous fluorescence, ANS fluorescence, far UV CD and ATR-FTIR spectroscopy
      show that the native mustard cystatin acquires a more ordered conformation upon
      interaction with metal ions. Differential Scanning Calorimetry indicates that the
      thermo-stability of the Ni2+ bound protein (Tm=109.4 degrees C) is greater than
      both, the Cd2+ bound (Tm=104.5 degrees C) and the native (Tm=99.5 degrees C)
      forms. The B. juncea seed cystatin, is thus, identified as a potent and resilient
      member of the phytocystatin family with considerable inhibitory capacity despite
      exposure to heavy metal stress.

PMID- 28754627
TI  - Therapeutic potentials of natural compounds acting on cyclic nucleotide
      phosphodiesterase families.
AB  - Intracellular cyclic AMP and/or cyclic GMP are characterized in the 1960th. These
      second messengers, hydrolysed specifically by cyclic nucleotide phosphodiesterase
      (PDE), play a major role in intracellular signalling. Natural products have been
      a rich source of drug discovery, Theophylline and Methylxanthine originated from
      tea leaves used for asthma treatment, whereas, Papaverine, a natural isoquinolein
      originated from Papaver somniferum traditionally used in impotency, altogether as
      caffeine where firstly described as PDE-inhibiting compounds. Since that time,
      the knowledge in PDE field has been drastically increased, allowing the design
      and development of new therapeutic drugs acting against different pathologies in
      the nanomolar range. During this period some natural compounds have been
      identified as PDE inhibitors and used in that context to investigate their
      therapeutic potential effects. The aim of this literature review is to point out
      the reported data and demonstrating the contribution of natural characterized
      molecules as PDE inhibitors in various pathologies that can open new fields of
      research for drug discovery, notably in epigenetic regulation.

PMID- 28754628
TI  - Differential vulnerability to adverse nutritional conditions in male and female
      rats: Modulatory role of estradiol during development.
AB  - Many studies have shown the importance of an adequate nutritional environment
      during development to optimally establish the neurohormonal circuits that
      regulate feeding behavior. Under- or over-nutrition during early stages of life
      can lead to alterations in the physiology and brain networks that control food
      intake, resulting in a greater vulnerability to suffer maladjustments in energy
      metabolism in adulthood. These alterations produced by under- or over-nourishment
      during development differ between males and females, as does the modulatory
      action that estradiol exerts on the alterations produced by malnutrition.
      Estradiol regulates metabolism and brain metabolic circuits through the same
      transcription factor pathway, STAT3, that leptin and ghrelin use to program
      feeding circuits. Although more research is needed to disentangle the actual role
      of estradiol during development on the programming of feeding circuits, a
      synergistic role together with leptin and/or ghrelin might be hypothesized.

PMID- 28754629
TI  - Connecting metabolism and gonadal function: Novel central neuropeptide pathways
      involved in the metabolic control of puberty and fertility.
AB  - Albeit essential for perpetuation of species, reproduction is an energy-demanding
      function that can be adjusted to body metabolic status. Reproductive maturation
      and function can be suppressed in conditions of energy deficit, but can be
      altered also in situations of persistent energy excess, e.g., morbid obesity.
      This metabolic-reproductive integration, of considerable pathophysiological
      relevance to explain different forms of perturbed puberty and sub/infertility, is
      implemented by the concerted action of numerous central and peripheral
      regulators, which impinge at different levels of the hypothalamic-pituitary
      gonadal (HPG) axis, permitting a tight fit between nutritional/energy status and
      gonadal function. We summarize here the major physiological mechanisms whereby
      nutritional and metabolic cues modulate the maturation and function of the HPG
      axis. We will focus on recent progress on the major central neuropeptide
      pathways, including kisspeptins, neurokinin B and the products of POMC and NPY
      neurons, which convey metabolic information to GnRH neurons, as major
      hierarchical hub of our reproductive brain.

PMID- 28754630
TI  - Reproductive and developmental toxicology studies with gantenerumab in PS2APP
      transgenic mice.
AB  - Gantenerumab is intended for the treatment of Alzheimer's disease. It is a fully
      human recombinant monoclonal IgG1 which binds aggregated forms of amyloid beta
      such as Abeta oligomers, fibrils and neuritic amyloid plaques. A full package of
      developmental and reproductive toxicity (DART) studies was performed in the
      PS2APP double-transgenic mouse model of Alzheimer's disease. A combined fertility
      and embryo fetal development study and a pre-and post-natal development study
      were performed. The PS2APP mouse model allowed a more complete DART evaluation
      than would have been possible in conventional species or strains which do not
      express the target antigen of gantenerumab. No developmental or reproductive
      hazards were identified.

PMID- 28754631
TI  - The nuclear protein-coding gene ANKRD23 negatively regulates myoblast
      differentiation.
AB  - Muscle fiber formation is a complex process and subject to fine regulation of a
      variety of protein-coding genes and non-coding RNA. In this study, we identified
      a nuclear protein-coding gene ANKRD23 which was highly expressed in muscle.
      Quantitative real-time PCR, western blotting and immunofluorescence were used to
      detect the expression change of myoblast differentiation marker genes after
      knockdown and overexpression of ANKRD23. The results showed that the expression
      of myoblast differentiation marker genes were increased by interference and
      reduced by ANKRD23 overexpression, indicating that ANKRD23 played a negative role
      in the myoblast differentiation. Interestingly, we discovered a long non-coding
      RNA-AK004293 which was overlapped with the 3'UTR of ANKRD23 gene. Then we
      detected the effect of AK004293 on the expression of ANKRD23 and myoblast
      differentiation marker genes in C2C12 myoblasts. The results showed that AK004293
      had no significant effect on the expression of myoblast differentiation maker
      genes and ANKRD23. In conclusion, our results established the foundation for
      further studies about the regulation mechanism of ANKRD23 in muscle development.

PMID- 28754632
TI  - Small RNA profiling reveals important roles for miRNAs in Arabidopsis response to
      Bacillus velezensis FZB42.
AB  - Bacillus velezensis FZB42 (previously classified as Bacillus amyloliquefaciens
      FZB42) has been confirmed to successfully colonize plant roots and enhance
      defense response against pathogen infection. This study indicated that FZB42
      inoculation enhanced Arabidopsis defense response against Pseudomonas syringae
      DC3000 through inducing the expression of PR1, PDF1.2 and stomata closure. To
      further clarify the induced defense response at miRNA level, sRNA libraries from
      Arabidopsis roots inoculated with FZB42 and control were constructed and
      sequenced. The reads of 21nt and 24nt in length were the most abundant groups in
      FZB42-treated library and control library, respectively. 234 known miRNAs and 16
      novel miRNAs were identified. Among them, 11 known miRNAs and 4 novel miRNAs were
      differentially expressed after FZB42 inoculation. Moreover cis-elements (TC-rich
      repeats, TCA-element and CGTCA-motif) associated with plant defense were also
      found in the promoters of these miRNAs. Additionally, 141 mRNAs were predicted as
      potential targets of these differentially expressed miRNAs. GO annotations of the
      target genes indicated their potential roles in polyamine biosynthetic process
      and intracellular protein transport biological process, which may contribute to
      increased defense response. Our findings indicated that Bacillus velezensis FZB42
      inoculation altered the expression of Arabidopsis miRNAs and their target genes,
      which were associated with defense response.

PMID- 28754633
TI  - Hyperoside protects against hypoxia/reoxygenation induced injury in
      cardiomyocytes by suppressing the Bnip3 expression.
AB  - AIMS: Role of hyperoside in protecting cardiomyocytes from ischemia/reperfusion
      induced injury has been proved. However, possible protecting mechanisms remain
      unclear. To fix the problem, an essential pro-apoptotic protein Bnip3 was studied
      in our experiments. METHODS AND RESULTS: Neonatal rat cardiomyocytes were used
      and submitted to hypoxia for 8h followed by reoxygenation for 2h to simulate the
      ischemia/reperfusion injury. Hypoxia/reoxygenation(H/R) induced damage to
      cardiomyocytes and the protective effect of hyperoside were examined by means of
      MTT assay. H/R-induced apoptosis was assessed by Terminal-deoxynucleoitidyl
      Transferase Mediated Nick End Labeling(TUNEL) and DNA Ladder assay. mRNA
      expression of Bnip3 was determined by use of quantitative real-time reverse
      transcription polymerase chain reaction assay. Protein levels of Bnip3, Bax, Bcl
      2 and cleaved caspase-3 were examined using western-blot assay. Our results
      showed that H/R caused great damage to cardiomyocytes, upregulated the protein
      expressions of Bnip3, Bax, cleaved caspase3, and decreased the expression of the
      anti-apoptotic protein of Bcl-2. Whereas, compared with the H/R group, a decrease
      in activities of Bnip3, Bax, cleaved caspase3, and a promoting expression of Bcl
      2 were detected in the H/R goup pretreated with hyperoside. CONCLUSION: It was
      concluded in our study that H/R-induced apoptotic effect in cardiomyocytes could
      be attenuated by hyperoside, and the protective role of hyperoside, if not
      completely, could be partly through the suppression of the pro-apoptotic gene
      Bnip3.

PMID- 28754634
TI  - An androgen-regulated miR-2909 modulates TGFbeta signalling through AR/miR-2909
      axis in prostate cancer.
AB  - In recent years, microRNAs (miRNAs) have emerged as promising biomarkers for PCa
      diagnosis and prognosis. miR-2909 is a novel miRNA that can regulate
      immunogenomics and oncogenomics. The present study investigated the role of miR
      2909 in the pathogenesis of PCa and the potential signalling pathways through
      which it operates. We have identified miR-2909 as a novel mediator of
      androgen/androgen receptor (AR) signalling that enhances the proliferation
      potential of PCa cells and assists in cancer survival under reduced androgen
      levels. Our results revealed that miR-2909 down regulates TGFBR2 by targeting its
      3'-UTR sequence. We also observed that miR-2909 over-expression attenuated
      TGFbeta-mediated SMAD3 activation, cell growth inhibition and apoptosis.
      Moreover, miR-2909 modulated the expression of p21CIP, c-MYC and CCND1 through
      TGFbeta signalling. Importantly, we also demonstrated that miR-2909 and AR
      regulates each other's expression resulting in a positive feedback loop. In
      conclusion, our study suggests that miR-2909 is an androgen-inducible miRNA that
      exerts its oncogenic effects by attenuating the tumor-suppressive effects of
      TGFbeta signalling.

PMID- 28754635
TI  - The little brown bat nuclear genome contains an entire mitochondrial genome: Real
      or artifact?
AB  - Nuclear mitochondrial DNA sequences (NUMTs) have been documented in almost all
      eukaryotic genomes studied. Recently, with the number of sequenced genomes
      increasing, extremely large NUMTs, even a nearly entire mitochondrial genome,
      have been reported in some plants and animals. However, few such studies provided
      strong experimental evidences for these important discoveries. In this study
      using a computer-based search method an entire mitochondrial genome (NUMT-1) was
      found in the nuclear genome of a bat species (Myotis lucifugus). This super-large
      NUMT shared a same scaffold with a 754bp nuclear genomic sequence and a second
      NUMT (NUMT-2, 3292bp). If NUMT-1 was real, it will be the largest NUMT found in
      animals and this finding will provide valuable insights into the mode of
      generation of NUMTs in the nuclear genome. Unfortunately, although the initial
      sequencing technology of the published M. lucifugus genome makes the possibility
      of artifact less likely, our results from both the PCR amplification followed by
      Sanger sequencing and mapping method based on the whole-genome resequencing
      datasets suggested that the scaffold containing the entire mitochondrial genome
      was artifact possibly due to a misassembly of mitochondrial and the nuclear DNA
      sequences. Our current study highlights the necessity to validate the
      authenticity of extremely large NUMTs identified in previous searches on whole
      genome sequence assemblies.

PMID- 28754636
TI  - Molecular cloning, characterization, and expression of duck 2'-5'-oligoadenylate
      synthetase-like gene.
AB  - 2'-5'-Oligoadenylate synthetase-like protein (OASL) is an interferon-inducible
      antiviral protein that exerts antiviral effects through the RNase L- or retinoic
      acid-inducible gene I (RIG-I)-dependent signalling pathway. In this study, we
      identified and cloned the OASL gene (named duOASL) from healthy adult Cherry
      Valley ducks. Full-length duOASL cDNA (1630bp) encoded a 504-amino acid
      polypeptide containing three conserved domains, namely, nucleotidyltransferase
      domain, 2'-5'-oligoadenylate synthetase domain, and two ubiquitin-like repeats.
      DuOASL mRNA expression was quantified by performing quantitative reverse
      transcription-PCR (qRT-PCR). Results of qRT-PCR showed that duOASL was broadly
      expressed in all examined tissues, with the highest mRNA expression in the large
      intestine. Antiviral activity of duOASL was measured by determining its effect on
      Duck Tembusu virus (DTMUV) replication in vitro. We found that duOASL
      overexpression slightly inhibited DTMUV replication, whereas duOASL knockdown by
      using a specific small interfering RNA increased DTMUV replication in DF-1 cells.
      Thus, we successfully cloned and characterized the antiviral protein duOASL from
      Cherry Valley ducks and found that it exerted antiviral effects against DTMUV.
      These results provide a solid foundation for performing further studies to
      determine the mechanism underlying the antiviral effect of duOASL at the cellular
      level.

PMID- 28754638
TI  - Microvascular Decompression for Trigeminal Neuralgia Using a Novel Fenestrated
      Clip and Tentorial Flap Technique.
AB  - BACKGROUND: Microvascular decompression (MVD) for neurovascular compression
      syndromes, such as trigeminal neuralgia and hemifacial spasm, has been
      traditionally described as an interposing technique using Teflon. Some
      alternative interposing materials have been proposed. In addition, transposing
      techniques have been increasingly reported as an alternative with a potentially
      lower recurrence rate and fewer complications. OBJECTIVE: To describe our
      experience with a technique consisting of transposition of the superior
      cerebellar artery using a fenestrated clip and a tentorial flap in patients with
      trigeminal neuralgia. METHODS: We describe a novel transposing technique using a
      fenestrated clip and a tentorial flap in patients with neurovascular compression.
      An illustrative case is provided of an 83-year-old female patient who complained
      of a 4-year history of left trigeminal neuralgia caused by compression by the
      superior cerebellar artery who was treated with this technique. Furthermore, a
      thorough review of the literature is presented. RESULTS: The patient underwent
      the procedure with the proposed technique without complication. Both the surgery
      and the postoperative course were uneventful. The patient remains asymptomatic 1
      year after the procedure. CONCLUSION: We propose a novel technique for the
      treatment of trigeminal neuralgia, eliminating the need for padding the vessel
      with a foreign body. This technique can be applied successfully in selected cases
      of neurovascular compression syndromes.

PMID- 28754637
TI  - The perilipin family of lipid droplet proteins: Gatekeepers of intracellular
      lipolysis.
AB  - Lipid droplets in chordates are decorated by two or more members of the perilipin
      family of lipid droplet surface proteins. The perilipins sequester lipids by
      protecting lipid droplets from lipase action. Their relative expression and
      protective nature is adapted to the balance of lipid storage and utilization in
      specific cells. Most cells of the body have tiny lipid droplets with perilipins 2
      and 3 at the surfaces, whereas specialized fat-storing cells with larger lipid
      droplets also express perilipins 1, 4, and/or 5. Perilipins 1, 2, and 5 modulate
      lipolysis by controlling the access of lipases and co-factors of lipases to
      substrate lipids stored within lipid droplets. Although perilipin 2 is relatively
      permissive to lipolysis, perilipins 1 and 5 have distinct control mechanisms that
      are altered by phosphorylation. Here we evaluate recent progress toward
      understanding functions of the perilipins with a focus on their role in
      regulating lipolysis and autophagy. This article is part of a Special Issue
      entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and
      Matthijs Hesselink.

PMID- 28754639
TI  - Bevacizumab for Radiation Induced Optic Neuritis Among Aggressive
      Residual/Recurrent Suprasellar Tumors: More Than a Mere Antineoplastic Effect.
AB  - BACKGROUND: Angiogenesis and vascular endothelial growth factor (VEGF) have
      recently been implicated in animal and clinical models of radiation-induced optic
      nerve, retinal, and brain necrosis. Although there are isolated case reports of
      anti-VEGF therapy with bevacizumab for management of radiation-induced brain
      necrosis, there are little data defining its role in radiation-induced optic
      nerve damage. PATIENTS AND METHODS: This study included patients with a sellar
      suprasellar tumor who underwent intensity-modulated or Gamma Knife radiotherapy
      and developed radiation-induced optic neuritis (RION) refractory to 3 weeks of
      glucocorticoid therapy who received bevacizumab 5 mg/kg intravenously as initial
      dose, followed by subsequent doses of 10 mg/kg. RESULTS: Here we report 3
      patients with sellar-suprasellar lesions undergoing conventional radiation
      therapy (2 cases) or Gamma Knife surgery (1 case) who had benefitted from anti
      VEGF therapy following radiation-induced optic nerve damage. CONCLUSIONS: Early
      bevacizumab therapy in steroid-refractory RION shows gratifying results.

PMID- 28754640
TI  - The Pathogenesis of Chronic Subdural Hematomas: A Study on the Formation of
      Chronic Subdural Hematomas and Analysis of Computed Tomography Findings.
AB  - BACKGROUND: The origin of chronic subdural hematomas (CSDH) and the
      pathophysiology of its enlargement remain unknown. The chemical fluid composition
      of CSDH, the contribution of cerebrospinal fluid (CSF) to its enlargement, and
      the relationship to its appearance on computed tomography (CT) also are not
      entirely clear. METHODS: In this prospective study, 58 samples in 41 patients
      treated surgically for CSDH were analyzed. CSDHs were evaluated for the presence
      of CSF via beta-2 transferrin and substances related to cell breakdown and
      hemolysis. These were compared with normal value of those substances in the serum
      and the CT appearances of the CSDH. RESULTS: In this study, 24% of the samples
      contained beta-2 transferrin, which was statistically significant. Total protein,
      lactate dehydrogenase, total bilirubin, and red blood cells also were
      statistically different when compared with their normal serum concentration,
      indicating an active process of rebleeding and hemolysis rather than plasma
      ultrafiltration; however, their concentrations did not correlate with specific CT
      scan appearance. The absence of CSF in CSDH in 76% of cases did not support the
      theory that most CSDHs originate from subdural hygromas. The presence of
      hemolysis and cell breakdown, byproducts supports the hypothesis that the primary
      enlargement of CSDH develops through neomembrane and neovascular formation,
      rebleeding, and inhibition of the blood coagulation process. Our study did not
      test for serum transudation as a component of the enlargement of CSDH.
      CONCLUSIONS: Our study confirms that the origin and enlargement of CSDH is
      multifactorial, but the contribution of individual factors and condition under
      which it occurs still remains unclear. CT scan findings do not correlate with the
      chemical composition or the presence of CSF in the CSDH.

PMID- 28754641
TI  - Improving the Prognostic Value of Disease-Specific Graded Prognostic Assessment
      Model for Renal Cell Carcinoma by Incorporation of Cumulative Intracranial Tumor
      Volume.
AB  - BACKGROUND: We tested the prognostic value of cumulative intracranial tumor
      volume (CITV) in the context of a disease-specific Graded Prognostic Assessment
      (ds-GPA) model for renal cell carcinoma (RCC) patients with brain metastasis (BM)
      treated with stereotactic radiosurgery (SRS). METHODS: Patient and tumor
      characteristics were collected from RCC cohorts with new BM who underwent SRS.
      Univariable and multivariable logistic regression model was used to test the
      prognostic value of CITV, Karnofsky Performance Score (KPS), and the number of
      BM. Net reclassification index (NRI) and integrated discrimination improvement
      (IDI) were used to assess whether CITV improved the prognostic utility of RCC ds
      GPA. RESULTS: In univariable logistic regression models, CITV, KPS, and the
      number of BM were independently associated with RCC patient survival. In a
      multivariable Cox proportional hazard model, the association between CITV and
      survival remained robust after controlling for KPS and the number of BM (P =
      0.042). The incorporation of the CITV into the RCC ds-GPA model (consisting of
      KPS and number of BM) improved prognostic accuracy with NRI >0 of 0.3156 (95%
      confidence interval [CI], 0.0883-0.5428; P = 0.0065) and IDI of 0.0151 (95% CI,
      0.0036-0.0277; P = 0.0183). These findings were validated in an independent
      cohort of 107 SRS-treated RCC BM patients. CONCLUSION: CITV is an important
      prognostic variable in SRS-treated RCC patients with BM. The prognostic value of
      the ds-GPA scale for RCC brain metastasis was enhanced by the incorporation of
      CITV.

PMID- 28754642
TI  - Symptomatic Thoracic Nerve Root Herniation into an Extradural Arachnoid Cyst:
      Case Report and Review of the Literature.
AB  - BACKGROUND: Spinal extradural arachnoid cysts (SEACs) are relatively rare and
      usually asymptomatic. They preferentially are situated in the thoracic extradural
      space and almost always dorsal. SEACs may present with back pain and/or cord
      compression symptoms. Needle aspiration, needle fenestration, or open surgical
      resection/fenestration have been reported as treatment modalities. CASE
      DESCRIPTION: We present a 35-year-old woman who complained of radiating pain from
      the right lower thoracic region of her back toward the right inguinal region,
      which was aggravated upon defecation and straining. Magnetic resonance imaging
      (MRI) revealed an extradural cyst located laterally at T11-T12 level on the
      right, with a nerve root herniation. During a T11-T12 hemilaminectomy, on
      resection of the cyst wall, a nerve root was noted to be herniating into the cyst
      cavity through a dural defect. The nerve root was released and repositioned
      intradurally, followed by direct suture of the dural tear. Histologic findings of
      the cyst wall confirmed an arachnoid cyst. Postoperative course was uneventful
      without complications. Postoperative MRI confirmed a complete resection of the
      cyst. Five years after surgery, the patient is asymptomatic with complete
      recovery. CONCLUSIONS: Thoracic SEACs can present with radiating pain due to a
      transdural herniation of a thoracic nerve root into the cyst, potentially due to
      a mechanism of intermittent pressure gradients between the intradural and
      extradural spaces. MRI can prove beneficial in visualizing the nerve prolapsing
      into the cyst. Open resection of the cyst wall, reduction of the nerve root
      herniation, and subsequent direct closure of the dural tear led to complete
      recovery.

PMID- 28754643
TI  - Probabilistic Tractography of the Cranial Nerves in Vestibular Schwannoma.
AB  - OBJECTIVE: Multiple recent studies have reported on diffusion tensor-based fiber
      tracking of cranial nerves in vestibular schwannoma, with conflicting results as
      to the accuracy of the method and the occurrence of cochlear nerve depiction.
      Probabilistic nontensor-based tractography might offer advantages in terms of
      better extraction of directional information from the underlying data in cranial
      nerves, which are of subvoxel size. METHODS: Twenty-one patients with large
      vestibular schwannomas were recruited. The probabilistic tracking was run
      preoperatively and the position of the potential depictions of the facial and
      cochlear nerves was estimated postoperatively by 3 independent observers in a
      blinded fashion. The true position of the nerve was determined intraoperatively
      by the surgeon. Thereafter, the imaging-based estimated position was compared
      with the intraoperatively determined position. Tumor size, cystic appearance, and
      postoperative House-Brackmann score were analyzed with regard to the accuracy of
      the depiction of the nerves. RESULTS: The probabilistic tracking showed a
      connection that correlated to the position of the facial nerve in 81% of the
      cases and to the position of the cochlear nerve in 33% of the cases. Altogether,
      the resulting depiction did not correspond to the intraoperative position of any
      of the nerves in 3 cases. CONCLUSIONS: In a majority of cases, the position of
      the facial nerve, but not of the cochlear nerve, could be estimated by evaluation
      of the probabilistic tracking results. However, false depictions not
      corresponding to any nerve do occur and cannot be discerned as such from the
      image only.

PMID- 28754644
TI  - Subdural Fluid Collection and Hydrocephalus After Foramen Magnum Decompression
      for Chiari Malformation Type I: Management Algorithm of a Rare Complication.
AB  - BACKGROUND: Chiari malformation type I is a hindbrain abnormality characterized
      by descent of the cerebellar tonsils beneath the foramen magnum, frequently
      associated with symptoms or brainstem compression, impaired cerebrospinal fluid
      circulation, and syringomyelia. Foramen magnum decompression represents the most
      common way of treatment. Rarely, subdural fluid collection and hydrocephalus
      represent postoperative adverse events. The treatment of this complication is
      still debated, and physicians are sometimes uncertain when to perform diversion
      surgery and when to perform more conservative management. CASE DESCRIPTION: We
      report an unusual occurrence of subdural fluid collection and hydrocephalus that
      developed in a 23-year-old patient after foramen magnum decompression for Chiari
      malformation type I. Following a management protocol, based on a step-by-step
      approach, from conservative therapy to diversion surgery, the patient was managed
      with urgent external ventricular drainage, and then with conservative management
      and wound revision. CONCLUSIONS: Because of the rarity of this adverse event,
      previous case reports differ about the form of treatment. In future cases,
      finding clinical and radiologic features to identify risk factors that are useful
      in predicting if the patient will benefit from conservative management or will
      need to undergo diversion surgery is only possible if a uniform form of treatment
      is used. Therefore, we believe that a management algorithm based on a step-by
      step approach will reduce the use of invasive therapies and help to create a
      standard of care.

PMID- 28754645
TI  - Accuracy of Novel Computed Tomography-Guided Frameless Stereotactic Drilling and
      Catheter System in Human Cadavers.
AB  - OBJECTIVE: To evaluate accuracy of a computed tomography (CT)-guided frameless
      stereotactic drilling and catheter system. METHODS: A prospective, single-arm
      study was performed using human cadaver heads to evaluate placement accuracy of a
      novel, flexible intracranial catheter and stabilizing bone anchor system and
      drill kit. There were 20 catheter placements included in the analysis. The
      primary endpoint was accuracy of catheter tip location on intraoperative CT.
      Secondary endpoints included target registration error and entry and target point
      error before and after drilling. Measurements are reported as mean +/- SD
      (median, range). RESULTS: Target registration error was 0.46 mm +/- 0.26 (0.50
      mm, -1.00 to 1.00 mm). Two (10%) target point trajectories were negatively
      impacted by drilling. Intracranial catheter depth was 59.8 mm +/- 9.4 (60.5 mm,
      38.0-80.0 mm). Drilling angle was 22 degrees  +/- 9 (21 degrees , 7 degrees -45
      degrees ). Deviation between planned and actual entry point on CT was 1.04 mm +/-
      0.38 (1.00 mm, 0.40-2.00 mm). Deviation between planned and actual target point
      on CT was 1.60 mm +/- 0.98 (1.40 mm, 0.40-4.00 mm). No correlation was observed
      between intracranial catheter depth and target point deviation (accuracy)
      (Pearson coefficient 0.018) or between technician experience and accuracy
      (Pearson coefficient 0.020). There was no significant difference in accuracy with
      trajectories performed for different cadaver heads (P = 0.362). CONCLUSIONS:
      Highly accurate catheter placement is achievable using this novel flexible
      catheter and bone anchor system placed via frameless stereotaxy, with an average
      deviation between planned and actual target point of 1.60 mm +/- 0.98 (1.40 mm,
      0.40-4.00 mm).

PMID- 28754646
TI  - Nanoscale deformation mechanisms and yield properties of hydrated bone
      extracellular matrix.
AB  - : Bone features a hierarchical architecture combining antagonistic properties
      like toughness and strength. In order to better understand the mechanisms leading
      to this advantageous combination, its postyield and failure behaviour was
      analyzed on the length scale of a single lamella. Micropillars were compressed to
      large strains under hydrated conditions to measure their anisotropic yield and
      post-yield behaviour. An increase in strength compared to the macroscale by a
      factor of 1.55 and a strong influence of hydration with a decrease by 60% in
      yield stress compared to vacuum conditions were observed. Post-compression
      transmission electron microscopic analysis revealed anisotropic deformation
      mechanisms. In axial pillars, where fibrils were oriented along the loading axis,
      kink bands were observed and shear cracks emerged at the interface of ordered and
      disordered regions. Micromechanical analysis of fibril kinking allowed an
      estimate of the extrafibrillar matrix shear strength to be made: 120+/-40MPa.
      When two opposing shear planes met a wedge was formed, splitting the micropillar
      axially in a mode 1 crack. Making use of an analytical solution, the mode 1
      fracture toughness of bone extracellular matrix for splitting along the fibril
      direction was estimated to be 0.07MPam. This is 1-2 orders of magnitude smaller
      than on the macroscale, which may be explained by the absence of extrinsic
      toughening mechanisms. In transverse pillars, where fibrils were oriented
      perpendicular to the loading axis, cracks formed in regions where adverse fibril
      orientation reduced the local fracture resistance. This study underlines the
      importance of bone's hierarchical microstructure for its macroscopic strength and
      fracture resistance and the need to study structure-property relationships as
      well as failure mechanisms under hydrated conditions on all length scales.
      STATEMENT OF SIGNIFICANCE: Bone's hierarchical architecture combines toughness
      and strength. To understand the governing deformation mechanisms, its postyield
      behaviour was analyzed at the microscale. Micropillars were compressed in
      physiological solution; an increased strength compared to macroscale and an
      influence of hydration was found. Transmission electron microscopy revealed
      cracks forming in regions with adverse fibril orientation in transverse pillars.
      In axial pillars kink bands were observed and shear cracks emerged at the
      interface of ordered and disordered regions. It was estimated that bone's
      fracture toughness for splitting between fibrils is significantly smaller than on
      the macroscale. This study underlines the importance of bone's hierarchical
      microstructure and the need to study structure-property relationships on all
      length scales.

PMID- 28754647
TI  - Biomimetically grown apatite spheres from aggregated bioglass nanoparticles with
      ultrahigh porosity and surface area imply potential drug delivery and cell
      engineering applications.
AB  - : Here we communicate the generation of biomimetically grown apatite spheres from
      aggregated bioglass nanoparticles and the potential properties applicable for
      drug delivery and cell/tissue engineering. Ion releasing nanoparticulates of
      bioglass (85%SiO2-15%CaO) in a mineralizing medium show an intriguing dynamic
      phenomenon - aggregation, mineralization to apatite, integration and growth into
      micron-sized (1.5-3MUm) spheres. During the progressive ionic
      dissolution/precipitation reactions, nano-to-micro-morphology, glass-to-crystal
      composition, and the physico-chemical properties (porosity, surface area, and
      charge) change dynamically. With increasing reaction period, the apatite becomes
      more crystallized with increased crystallinity and crystal size, and gets a
      composition closer to the stoichiometry. The developed microspheres exhibit
      hierarchical surface nanostructure, negative charge (sigma-potential of -20mV),
      and ultrahigh mesoporosity (mesopore size of 6.1nm, and the resultant surface
      area of 63.7m2/g and pore volume of 0.153cm3/g) at 14days of mineralization,
      which are even higher than those of its precursor bioglass nanoparticles. Thanks
      to these properties, the biomimetic mineral microspheres take up biological
      molecules effectively, i.e., loading capacity of positive-charged protein is over
      10%. Of note, the release is highly sustainable at a constant rate, i.e.,
      profiling almost 'zero-order' kinetics for 4weeks, suggesting the potential
      usefulness as protein delivery systems. The biomimetic mineral microspheres hold
      some remnant Si in the core region, and release calcium, phosphate, and silicate
      ions over the test period, implying the long-term ionic-related therapeutic
      functions. The mesenchymal stem cells favour the biomimetic spheres with an
      excellent viability. Due to the merit of sizes (a few micrometers), the spheres
      can be intercalated into cells, mediating cellular interactions in 3D cell
      spheroid engineering, and also can stimulate osteogenic differentiation of cells
      when incorporated into cell-laden gels. The intriguing properties observed in
      this study, including biomimetic composition, high mesoporosity, release of
      therapeutic ions, effective loading and long-term release of proteins, and
      diverse yet favorable 3D cellular interactions, suggest great potential of the
      newly developed biomimetic microspheres in biomedical applications, such as drug
      delivery and cell/tissue engineering. STATEMENT OF SIGNIFICANCE: This work
      reports the generation of apatite spheres with a few micrometers in size
      biomimetically grown from bioactive glass nanoparticles, through a series of
      intriguing yet unprecedented phenomenon involving aggregation of nanoparticles,
      mineralization and sphere growth. The mineral microspheres possess some unique
      physico-chemical properties including mesoporosity, ultrahigh surface area, and
      therapeutic ionic release. Furthermore, the spheres show excellent loading and
      delivery capacity of protein molecules, and mediate favorable cellular
      interactions in 2D and 3D culture conditions, demonstrating a future
      multifunctional microcarrier platform for the therapeutics delivery and
      cell/tissue engineering.

PMID- 28754648
TI  - Microtopographical cues promote peripheral nerve regeneration via transient
      mTORC2 activation.
AB  - : Despite microsurgical repair, recovery of function following peripheral nerve
      injury is slow and often incomplete. Outcomes could be improved by an increased
      understanding of the molecular biology of regeneration and by translation of
      experimental bioengineering strategies. Topographical cues have been shown to be
      powerful regulators of the rate and directionality of neurite regeneration, and
      in this study we investigated the downstream molecular effects of linear
      micropatterned structures in an organotypic explant model. Linear topographical
      cues enhanced neurite outgrowth and our results demonstrated that the mTOR
      pathway is important in regulating these responses. mTOR gene expression peaked
      between 48 and 72h, coincident with the onset of rapid neurite outgrowth and
      glial migration, and correlated with neurite length at 48h. mTOR protein was
      located to glia and in a punctate distribution along neurites. mTOR levels peaked
      at 72h and were significantly increased by patterned topography (p<0.05).
      Furthermore, the topographical cues could override pharmacological inhibition.
      Downstream phosphorylation assays and inhibition of mTORC1 using rapamycin
      highlighted mTORC2 as an important mediator, and more specific therapeutic
      target. Quantitative immunohistochemistry confirmed the presence of the mTORC2
      component rictor at the regenerating front where it co-localised with F-actin and
      vinculin. Collectively, these results provide a deeper understanding of the
      mechanism of action of topography on neural regeneration, and support the
      incorporation of topographical patterning in combination with pharmacological
      mTORC2 potentiation within biomaterial constructs used to repair peripheral
      nerves. STATEMENT OF SIGNIFICANCE: Peripheral nerve injury is common and
      functionally devastating. Despite microsurgical repair, healing is slow and
      incomplete, with lasting functional deficit. There is a clear need to translate
      bioengineering approaches and increase our knowledge of the molecular processes
      controlling nerve regeneration to improve the rate and success of healing.
      Topographical cues are powerful determinants of neurite outgrowth and represent a
      highly translatable engineering strategy. Here we demonstrate, for the first
      time, that microtopography potentiates neurite outgrowth via the mTOR pathway,
      with the mTORC2 subtype being of particular importance. These results give
      further evidence for the incorporation of microtopographical cues into peripheral
      nerve regeneration conduits and indicate that mTORC2 may be a suitable
      therapeutic target to potentiate nerve regeneration.

PMID- 28754649
TI  - Stretching single fibrin fibers hampers their lysis.
AB  - : Blood clots, whose main structural component is a mesh of microscopic fibrin
      fibers, experience mechanical strain from blood flow, clot retraction and
      interactions with platelets and other cells. We developed a transparent, striated
      and highly stretchable substrate made from fugitive glue (a styrenic block
      copolymer) to investigate how mechanical strain affects lysis of single,
      suspended fibrin fibers. In this suspended fiber assay, lysis manifested itself
      by fiber elongation, thickening (disassembly), fraying and collapse. Stretching
      single fibrin fibers significantly hampered their lysis. This effect was seen in
      uncrosslinked and crosslinked fibers. Crosslinking (without stretching) also
      hampered single fiber lysis. Our data suggest that strain is a novel
      mechanosensitive factor that regulates blood clot dissolution (fibrinolysis) at
      the single fiber level. At the molecular level of single fibrin molecules, strain
      may distort, or hinder access to, plasmin cleavage sites and thereby hamper
      lysis. STATEMENT OF SIGNIFICANCE: Fibrin fibers are the major structural
      component of a blood clot. We developed a highly stretchable substrate made from
      fugitive glue and a suspended fibrin fiber lysis assay to investigate the effect
      of stretching on single fibrin fibers lysis. The key findings from our
      experiments are: 1) Fibers thicken and elongate upon lysis; 2) stretching
      strongly reduces lysis; 3) this effect is more pronounced for uncrosslinked
      fibers; and 4) stretching fibers has a similar effect on reducing lysis as
      crosslinking fibers. At the molecular level, strain may distort plasmin cleavage
      sites, or restrict access to those sites. Our results suggest that strain may be
      a novel mechanobiological factor that regulates fibrinolysis.

PMID- 28754650
TI  - Modeling Patient Treatment With Medical Records: An Abstraction Hierarchy to
      Understand User Competencies and Needs.
AB  - BACKGROUND: Health care is a complex sociotechnical system. Patient treatment is
      evolving and needs to incorporate the use of technology and new patient-centered
      treatment paradigms. Cognitive work analysis (CWA) is an effective framework for
      understanding complex systems, and work domain analysis (WDA) is useful for
      understanding complex ecologies. Although previous applications of CWA have
      described patient treatment, due to their scope of work patients were previously
      characterized as biomedical machines, rather than patient actors involved in
      their own care. OBJECTIVE: An abstraction hierarchy that characterizes patients
      as beings with complex social values and priorities is needed. This can help
      better understand treatment in a modern approach to care. The purpose of this
      study was to perform a WDA to represent the treatment of patients with medical
      records. METHODS: The methods to develop this model included the analysis of
      written texts and collaboration with subject matter experts. Our WDA represents
      the ecology through its functional purposes, abstract functions, generalized
      functions, physical functions, and physical forms. RESULTS: Compared with other
      work domain models, this model is able to articulate the nuanced balance between
      medical treatment, patient education, and limited health care resources. Concepts
      in the analysis were similar to the modeling choices of other WDAs but combined
      them in as a comprehensive, systematic, and contextual overview. The model is
      helpful to understand user competencies and needs. Future models could be
      developed to model the patient's domain and enable the exploration of the shared
      decision-making (SDM) paradigm. CONCLUSION: Our work domain model links treatment
      goals, decision-making constraints, and task workflows. This model can be used by
      system developers who would like to use ecological interface design (EID) to
      improve systems. Our hierarchy is the first in a future set that could explore
      new treatment paradigms. Future hierarchies could model the patient as a
      controller and could be useful for mobile app development.

PMID- 28754651
TI  - A Smartphone App for Adolescents With Sleep Disturbance: Development of the Sleep
      Ninja.
AB  - BACKGROUND: Sleep disturbances are common in young people and have consequences
      for academic, social, emotional, and behavioral development. The most effective
      treatment is cognitive behavioral therapy for insomnia (CBT-I), with evidence
      suggesting that it is efficacious even when delivered digitally. OBJECTIVE: There
      are no commercially available digitally delivered CBT-I programs for use by young
      people. The aim of this project was to develop a smartphone app that delivers CBT
      I to young people to improve sleep. METHODS: To inform the development of the
      app, young people (N=21) aged between 12 and 16 years attended one of the 3 focus
      groups (each with 4-10 participants). These focus groups were conducted at
      different stages of the development process such that the process could be
      iterative. Participants were asked the reasons why they might use an app to help
      them sleep, the kinds of features or functions that they would like to see in
      such an app, and any concerns they may have in using the app. Data were analyzed
      using a thematic analysis approach. Of the issues discussed by the participants,
      the researchers selected themes associated with content, functionality, and
      accessibility and user experience to examine, as these were most informative for
      the app design process. RESULTS: In terms of content, young people were
      interested in receiving information about recommended sleep guidelines and
      personalized information for their age group. They reported that keeping a sleep
      diary was acceptable, but they should be able to complete it flexibly, in their
      own time. They reported mixed views about the use of the phone's accelerometer.
      Young people felt that the functionality of the app should include elements of
      game playing if they were to remain engaged with the app. Flexibility of use and
      personalized features were also desirable, and there were mixed views about the
      schedule of notifications and reminders. Participants reported that for the app
      to be accessible and usable, it should be from a trusted developer, have engaging
      aesthetics, have a layout that is easy to navigate, not rely on Internet
      coverage, and preferably be free. Participants felt that being able to conceal
      the purpose of the app from peers was an advantage and were willing to provide
      personal information to use the app if the purpose and use of that information
      was made clear. Overall, participants endorsed the use of the app for sleep
      problems among their age group and reported motivation to use it. CONCLUSIONS:
      The Sleep Ninja is a fully-automated app that delivers CBT-I to young people,
      incorporating the features and information that young people reported they would
      expect from this app. A pilot study testing the feasibility, acceptability, and
      efficacy of the Sleep Ninja is now underway.

PMID- 28754652
TI  - Web-Based Interventions to Improve Mental Health, General Caregiving Outcomes,
      and General Health for Informal Caregivers of Adults With Chronic Conditions
      Living in the Community: Rapid Evidence Review.
AB  - BACKGROUND: Most adults with chronic conditions live at home and rely on informal
      caregivers to provide support. Caregiving can result in negative impacts such as
      poor mental and physical health. eHealth interventions may offer effective and
      accessible ways to provide education and support to informal caregivers. However,
      we know little about the impact of Web-based interventions for informal
      caregivers of community-dwelling adults with chronic conditions. OBJECTIVE: The
      purpose of this rapid evidence review was to assess the impact of Web-based
      interventions on mental health, general caregiving outcomes, and general health
      for informal caregivers of persons with chronic conditions living in the
      community. METHODS: A rapid evidence review of the current literature was
      employed to address the study purpose. EMBASE, MEDLINE, PsychInfo, CINAHL,
      Cochrane, and Ageline were searched covering all studies published from January
      1995 to July 2016. Papers were included if they (1) included a Web-based modality
      to deliver an intervention; (2) included informal, unpaid adult caregivers of
      community-living adults with a chronic condition; (3) were either a randomized
      controlled trial (RCT) or controlled clinical trial (CCT); and (4) reported on
      any caregiver outcome as a result of use or exposure to the intervention.
      RESULTS: A total of 20 papers (17 studies) were included in this review. Study
      findings were mixed with both statistically significant and nonsignificant
      findings on various caregiver outcomes. Of the 17 included studies, 10 had at
      least one significant outcome. The most commonly assessed outcome was mental
      health, which included depressive symptoms, stress or distress, and anxiety.
      Twelve papers examined the impact of interventions on the outcome of depressive
      symptoms; 4 found a significant decrease in depressive symptoms. Eight studies
      examined the outcome of stress or distress; 4 of these found a significant
      reduction in stress or distress as a result of the intervention. Three studies
      examined the outcome of anxiety; 2 of these found significant reductions in
      anxiety. Other significant results of the interventions were seen in the outcomes
      of caregiver gain (ie, positive aspects of caregiving), knowledge, bonding,
      reduction of anger-hostility, and negative mood. Based on this review, it is not
      possible to determine which interventions were most effective since studies
      differed in their design, sample, and intervention. Study results suggest that
      Web-based interventions may result in reduced depressive symptoms, anxiety, and
      stress or distress among informal caregivers of adults with chronic conditions in
      the community. CONCLUSIONS: This is the first review assessing the impact of Web
      based technologies on mental health, general caregiving outcomes, and general
      health for caregivers of adults with chronic conditions living in the community.
      Further rigorous research is needed that includes adequately powered studies
      examining the critical components of the intervention and the dosage needed to
      have an effect.

PMID- 28754653
TI  - Integrated Care in Prostate Cancer (ICARE-P): Nonrandomized Controlled
      Feasibility Study of Online Holistic Needs Assessment, Linking the Patient and
      the Health Care Team.
AB  - BACKGROUND: The potential of technology to aid integration of care delivery
      systems is being explored in a range of contexts across a variety of conditions
      in the United Kingdom. Prostate cancer is the most common cancer in UK men. With
      a 10-year survival rate of 84%, there is a need to explore innovative methods of
      care that are integrated between primary health care providers and specialist
      teams in order to address long-term consequences of the disease and its treatment
      as well as to provide continued monitoring for recurrence. OBJECTIVE: Our aim was
      to test the feasibility of a randomized controlled trial to compare a model of
      prostate cancer continuing and follow-up care integration, underpinned by digital
      technology, with usual care in terms of clinical and cost-effectiveness, patient
      reported outcomes, and experience. METHODS: A first phase of the study has
      included development of an online adaptive prostate specific Holistic Needs
      Assessment system (HNA), training for primary care-based nurses, training of an
      IT peer supporter, and interviews with health care professionals and men with
      prostate cancer to explore views of their care, experience of technology, and
      views of the proposed intervention. In Phase 2, men in the intervention arm will
      complete the HNA at home to help identify and articulate concerns and share them
      with their health care professionals, in both primary and specialist care.
      Participants in the control arm will receive usual care. Outcomes including
      quality of life and well-being, prostate-specific concerns, and patient
      enablement will be measured 3 times over a 9-month period. RESULTS: Findings from
      phase 1 indicated strong support for the intervention among men, including those
      who had had little experience of digital technology. Men expressed a range of
      views on ways that the online system might be used within a clinical pathway.
      Health care professionals gave valuable feedback on how the output of the
      assessment might be presented to encourage engagement and uptake by clinical
      teams. Recruitment to the second phase of the study, the feasibility trial,
      commenced March 2017. CONCLUSIONS: To our knowledge, this study is the first in
      the United Kingdom to trial an online holistic needs assessment for men with
      prostate cancer, with data shared between patients and primary and secondary care
      providers. This study addresses recommendations in recent policy documents
      promoting the importance of data sharing and enhanced communication between care
      providers as a basis for care integration. We anticipate that this model of care
      will ultimately provide important benefits for both patients and the National
      Health Service. TRIAL REGISTRATION: International Standard Randomized Controlled
      Trial Number (ISRCTN): 31380482; http://www.isrctn.com/ISRCTN31380482 (Archived
      by WebCite at http://www.webcitation.org/6s8I42u5N).

PMID- 28754654
TI  - Impact of Right Ventricular Performance in Patients Undergoing Extracorporeal
      Membrane Oxygenation Following Cardiac Surgery.
AB  - BACKGROUND: Extracorporeal membrane oxygenation following cardiac surgery
      safeguards end-organ oxygenation but unfavorably alters cardiac hemodynamics.
      Along with the detrimental effects of cardiac surgery to the right heart, this
      might impact outcome, particularly in patients with preexisting right ventricular
      (RV) dysfunction. We sought to determine the prognostic impact of RV function and
      to improve established risk-prediction models in this vulnerable patient cohort.
      METHODS AND RESULTS: Of 240 patients undergoing extracorporeal membrane
      oxygenation support following cardiac surgery, 111 had echocardiographic
      examinations at our institution before implantation of extracorporeal membrane
      oxygenation and were thus included. Median age was 67 years (interquartile range
      60-74), and 74 patients were male. During a median follow-up of 27 months
      (interquartile range 16-63), 75 patients died. Fifty-one patients died within 30
      days, 75 during long-term follow-up (median follow-up 27 months, minimum 5
      months, maximum 125 months). Metrics of RV function were the strongest predictors
      of outcome, even stronger than left ventricular function (P<0.001 for receiver
      operating characteristics comparisons). Specifically, RV free-wall strain was a
      powerful predictor univariately and after adjustment for clinical variables,
      Simplified Acute Physiology Score-3, tricuspid regurgitation, surgery type and
      duration with adjusted hazard ratios of 0.41 (95%CI 0.24-0.68; P=0.001) for 30
      day mortality and 0.48 (95%CI 0.33-0.71; P<0.001) for long-term mortality for a 1
      SD (SD=-6%) change in RV free-wall strain. Combined assessment of the additive
      EuroSCORE and RV free-wall strain improved risk classification by a net
      reclassification improvement of 57% for 30-day mortality (P=0.01) and 56% for
      long-term mortality (P=0.02) compared with the additive EuroSCORE alone.
      CONCLUSIONS: RV function is strongly linked to mortality, even after adjustment
      for baseline variables and clinical risk scores. RV performance improves
      established risk prediction models for short- and long-term mortality.

PMID- 28754655
TI  - Modeling Treatment Response for Lamin A/C Related Dilated Cardiomyopathy in Human
      Induced Pluripotent Stem Cells.
AB  - BACKGROUND: Precision medicine is an emerging approach to disease treatment and
      prevention that takes into account individual variability in the environment,
      lifestyle, and genetic makeup of patients. Patient-specific human induced
      pluripotent stem cells hold promise to transform precision medicine into real
      life clinical practice. Lamin A/C (LMNA)-related cardiomyopathy is the most
      common inherited cardiomyopathy in which a substantial proportion of mutations in
      the LMNA gene are of nonsense mutation. PTC124 induces translational read-through
      over the premature stop codon and restores production of the full-length proteins
      from the affected genes. In this study we generated human induced pluripotent
      stem cells-derived cardiomyocytes from patients who harbored different LMNA
      mutations (nonsense and frameshift) to evaluate the potential therapeutic effects
      of PTC124 in LMNA-related cardiomyopathy. METHODS AND RESULTS: We generated human
      induced pluripotent stem cells lines from 3 patients who carried distinctive
      mutations (R225X, Q354X, and T518fs) in the LMNA gene. The cardiomyocytes derived
      from these human induced pluripotent stem cells lines reproduced the
      pathophysiological hallmarks of LMNA-related cardiomyopathy. Interestingly,
      PTC124 treatment increased the production of full-length LMNA proteins in only
      the R225X mutant, not in other mutations. Functional evaluation experiments on
      the R225X mutant further demonstrated that PTC124 treatment not only reduced
      nuclear blebbing and electrical stress-induced apoptosis but also improved the
      excitation-contraction coupling of the affected cardiomyocytes. CONCLUSIONS:
      Using cardiomyocytes derived from human induced pluripotent stem cells carrying
      different LMNA mutations, we demonstrated that the effect of PTC124 is codon
      selective. A premature stop codon UGA appeared to be most responsive to PTC124
      treatment.

PMID- 28754656
TI  - STUB1 regulates TFEB-induced autophagy-lysosome pathway.
AB  - TFEB is a master regulator for transcription of genes involved in autophagy and
      lysosome biogenesis. Activity of TFEB is inhibited upon its serine
      phosphorylation by mTOR The overall mechanisms by which TFEB activity in the cell
      is regulated are not well elucidated. Specifically, the mechanisms of TFEB
      turnover and how they might influence its activity remain unknown. Here, we show
      that STUB1, a chaperone-dependent E3 ubiquitin ligase, modulates TFEB activity by
      preferentially targeting inactive phosphorylated TFEB for degradation by the
      ubiquitin-proteasome pathway. Phosphorylated TFEB accumulated in STUB1-deficient
      cells and in tissues of STUB1-deficient mice resulting in reduced TFEB activity.
      Conversely, cellular overexpression of STUB1 resulted in reduced phosphorylated
      TFEB and increased TFEB activity. STUB1 preferentially interacted with and
      ubiqutinated phosphorylated TFEB, targeting it to proteasomal degradation.
      Consistent with reduced TFEB activity, accumulation of phosphorylated TFEB in
      STUB1-deficient cells resulted in reduced autophagy and reduced mitochondrial
      biogenesis. These studies reveal that the ubiquitin-proteasome pathway
      participates in regulating autophagy and lysosomal functions by regulating the
      activity of TFEB.

PMID- 28754658
TI  - Deciphering the regulation of metabolism with dynamic optimization: an overview
      of recent advances.
AB  - Understanding optimality principles shaping the evolution of regulatory networks
      controlling metabolism is crucial for deriving a holistic picture of how
      metabolism is integrated into key cellular processes such as growth, adaptation
      and pathogenicity. While in the past the focus of research in pathway regulation
      was mainly based on stationary states, more recently dynamic optimization has
      proved to be an ideal tool to decipher regulatory strategies for metabolic
      pathways in response to environmental cues. In this short review, we summarize
      recent advances in the elucidation of optimal regulatory strategies and
      identification of optimal control points in metabolic pathways. We discuss
      biological implications of the discovered optimality principles on genome
      organization and provide examples how the derived knowledge can be used to
      identify new treatment strategies against pathogens. Furthermore, we briefly
      discuss the variety of approaches for solving dynamic optimization problems and
      emphasize whole-cell resource allocation models as an important emerging area of
      research that will allow us to study the regulation of metabolism on the whole
      cell level.

PMID- 28754657
TI  - Recombination at subtelomeres is regulated by physical distance, double-strand
      break resection and chromatin status.
AB  - Homologous recombination (HR) is a conserved mechanism that repairs broken
      chromosomes via intact homologous sequences. How different genomic, chromatin and
      subnuclear contexts influence HR efficiency and outcome is poorly understood. We
      developed an assay to assess HR outcome by gene conversion (GC) and break-induced
      replication (BIR), and discovered that subtelomeric double-stranded breaks (DSBs)
      are preferentially repaired by BIR despite the presence of flanking homologous
      sequences. Overexpression of a silencing-deficient SIR3 mutant led to active
      grouping of telomeres and specifically increased the GC efficiency between
      subtelomeres. Thus, physical distance limits GC at subtelomeres. However, the
      repair efficiency between reciprocal intrachromosomal and subtelomeric sequences
      varies up to 15-fold, depending on the location of the DSB, indicating that
      spatial proximity is not the only limiting factor for HR EXO1 deletion limited
      the resection at subtelomeric DSBs and improved GC efficiency. The presence of
      repressive chromatin at subtelomeric DSBs also favoured recombination, by
      counteracting EXO1-mediated resection. Thus, repressive chromatin promotes HR at
      subtelomeric DSBs by limiting DSB resection and protecting against genetic
      information loss.

PMID- 28754659
TI  - Stress-Induced Sleep After Exposure to Ultraviolet Light Is Promoted by p53 in
      Caenorhabditis elegans.
AB  - Stress-induced sleep (SIS) in Caenorhabditis elegans is important for restoration
      of cellular homeostasis and is a useful model to study the function and
      regulation of sleep. SIS is triggered when epidermal growth factor (EGF)
      activates the ALA neuron, which then releases neuropeptides to promote sleep. To
      further understand this behavior, we established a new model of SIS using
      irradiation by ultraviolet C (UVC) light. While UVC irradiation requires ALA
      signaling and leads to a sleep state similar to that induced by heat and other
      stressors, it does not induce the proteostatic stress seen with heat exposure.
      Based on the known genotoxic effects of UVC irradiation, we tested two genes, atl
      1 and cep-1, which encode proteins that act in the DNA damage response pathway.
      Loss-of-function mutants of atl-1 had no defect in UVC-induced SIS but a partial
      loss-of-function mutant of cep-1, gk138, had decreased movement quiescence
      following UVC irradiation. Germline ablation experiments and tissue-specific RNA
      interference experiments showed that cep-1 is required somatically in neurons for
      its effect on SIS. The cep-1(gk138) mutant suppressed body movement quiescence
      controlled by EGF, indicating that CEP-1 acts downstream or in parallel to ALA
      activation to promote quiescence in response to ultraviolet light.

PMID- 28754660
TI  - Selection During Maize Domestication Targeted a Gene Network Controlling Plant
      and Inflorescence Architecture.
AB  - Selection during evolution, whether natural or artificial, acts through the
      phenotype. For multifaceted phenotypes such as plant and inflorescence
      architecture, the underlying genetic architecture is comprised of a complex
      network of interacting genes rather than single genes that act independently to
      determine the trait. As such, selection acts on entire gene networks. Here, we
      begin to define the genetic regulatory network to which the maize domestication
      gene, teosinte branched1 (tb1), belongs. Using a combination of molecular methods
      to uncover either direct or indirect regulatory interactions, we identified a set
      of genes that lie downstream of tb1 in a gene network regulating both plant and
      inflorescence architecture. Additional genes, known from the literature, also act
      in this network. We observed that tb1 regulates both core cell cycle genes and
      another maize domestication gene, teosinte glume architecture1 (tga1). We show
      that several members of the MADS-box gene family are either directly or
      indirectly regulated by tb1 and/or tga1, and that tb1 sits atop a cascade of
      transcriptional regulators controlling both plant and inflorescence architecture.
      Multiple members of the tb1 network appear to have been the targets of selection
      during maize domestication. Knowledge of the regulatory hierarchies controlling
      traits is central to understanding how new morphologies evolve.

PMID- 28754661
TI  - Predicting Amino Acid Substitution Probabilities Using Single Nucleotide
      Polymorphisms.
AB  - Fast genome sequencing offers invaluable opportunities for building updated and
      improved models of protein sequence evolution. We here show that Single
      Nucleotide Polymorphisms (SNPs) can be used to build a model capable of
      predicting the probability of substitution between amino acids in variants of the
      same protein in different species. The model is based on a substitution matrix
      inferred from the frequency of codon interchanges observed in a suitably selected
      subset of human SNPs, and predicts the substitution probabilities observed in
      alignments between Homo sapiens and related species at 85-100% of sequence
      identity better than any other approach we are aware of. The model gradually
      loses its predictive power at lower sequence identity. Our results suggest that
      SNPs can be employed, together with multiple sequence alignment data, to model
      protein sequence evolution. The SNP-based substitution matrix developed in this
      work can be exploited to better align protein sequences of related organisms, to
      refine the estimate of the evolutionary distance between protein variants from
      related species in phylogenetic trees and, in perspective, might become a useful
      tool for population analysis.

PMID- 28754662
TI  - Shock-absorbing aggregates beneath playground equipment: grain properties and
      moisture content.
AB  - OBJECTIVES: To assess the influence of grain size distribution and moisture
      condition on aggregates'Setting and methodsImpact attenuation of sands and
      gravels was tested using a guided headform with a uniaxial accelerometer inside.
      The result for impact attenuation was the acceleration value of the headform
      measured from four different drop heights and the Head Injury Criterion (HIC)
      calculated from it. The acceptable HIC value of a shock-absorbing layer is <1000,
      that is, less than the critical fall height. Tests were conducted with both dry
      and wet materials. RESULTS: The impact attenuation of a shock-absorbing layer
      made of loose aggregate is determined mainly by the following material factors:
      maximum grain size, median grain size, uniformity coefficient, fines content,
      grain shape and moisture content. In addition, the moisture content of aggregate,
      especially sands, has a major impact on its impact attenuation capacity. Of the
      studied sands, coarse and gravelly ones had the best impact attenuation
      properties. Most of the examined sands were uniformly graded. None of the grain
      properties of gravels proved more significant than the others. Yet, open-graded
      gravel (dominant grain size 4-8 mm) containing a small amount (about10%) of sand
      fraction 0.06-0.6 mm, but with hardly any coarse sand (0.6-2 mm), was found to
      have good impact attenuation. CONCLUSIONS: This study shows that the aggregates
      for shock-absorbing layer should always be tested wet in laboratory conditions
      corresponding the most critical situation. Standards should include a procedure
      for wet testing of aggregates.

PMID- 28754663
TI  - Assessment of short reports using a human rights-based approach to tobacco
      control to the Commitee on Economics, Cultural and Social Rights.
AB  - BACKGROUND: The health impact of tobacco use remains a major global public health
      concern and a human rights issue. The Human Rights and Tobacco Control Network
      (HRTCN) was established to increase the visibility of tobacco as a human rights
      issue. HRTCN submitted short reports to the UN Committee on Economic Social and
      Cultural Rights evaluating individual nations' tobacco control policies and
      offering recommendations. METHODS: HRTCN reviewed Concluding Observations
      documents for nations for which the HRTCN submitted reports. If tobacco was
      mentioned in the Concluding Observations through acknowledging the Framework
      Convention on Tobacco Control ratification, policy changes or discussing tobacco
      in the recommendations, this was scored as a positive finding. HRTCN also
      reviewed Concluding Observations for nations for which HRTCN did not submit
      reports as a comparison. RESULTS: Thirty-eight HRTCN reports were submitted and
      tobacco was mentioned in Concluding Observations for 11 nations for a rate of
      28.9%. In a comparison set of Concluding Observations (n=59), 7% had comments or
      recommendations relative to tobacco. CONCLUSIONS: This was not a controlled study
      and the 28.9% 'success rate' for impacting the Concluding Observations, although
      encouraging, is less than optimal-and leaves room for improvement. The higher
      rate of tobacco mentions for the cases where the HRTCN short reports were
      submitted provides preliminary indications that the short reports may have
      potential to increase the state focus on tobacco control. Future work will seek
      to improve the design and scope of the reports, and the specificity of the
      background information and recommendations offered.

PMID- 28754665
TI  - Multiparametric Detection of Antibodies against Different EBV Antigens to Predict
      Risk for Nasopharyngeal Carcinoma in a High-Risk Population of China.
AB  - In this study, we aimed to use the combined detection of multiple antibodies
      against Epstein-Barr virus (EBV) antigens to develop a model for screening and
      diagnosis of nasopharyngeal carcinoma (NPC). Samples of 300 nasopharyngeal
      carcinoma patients and 494 controls, including 294 healthy subjects (HC), 99 non
      nasopharyngeal carcinoma cancer patients (NNPC), and 101 patients with benign
      nasopharyngeal lesions (BNL), were incubated with the EUROLINE Anti-EBV Profile
      2, and band intensities were used to establish a risk prediction model. The
      nasopharyngeal carcinoma risk probability analysis based on the panel of VCAgp125
      IgA, EBNA-1 IgA, EA-D IgA, EBNA-1 IgG, EAD IgG, and VCAp19 IgG displayed the best
      performance. When using 26.1% as the cutoff point in ROC analysis, the AUC value
      and sensitivity/specificity were 0.951 and 90.7%/86.2%, respectively, in
      nasopharyngeal carcinoma and all controls. In nasopharyngeal carcinoma and
      controls without the non-nasopharyngeal carcinoma and BNL groups, the AUC value
      and sensitivity/specificity were 0.957 and 90.7%/88.1%, respectively. The
      diagnostic specificity and sensitivity of the EUROLINE Anti-EBV Profile 2 assay
      for both nasopharyngeal carcinoma and early-stage nasopharyngeal carcinoma were
      higher than that of mono-antibody detection by immune-enzymatic assay and real
      time PCR (EBV DNA). In the VCA-IgA-negative group, 82.6% of nasopharyngeal
      carcinoma patients showed high probability for nasopharyngeal carcinoma, and the
      negative predictive value was 97.1%. In the VCA-IgA-positive group, 73.3% of
      healthy subjects showed low probability. The positive predictive value reached
      98.2% in this group. The nasopharyngeal carcinoma risk probability value
      determined by the EUROLINE Anti-EBV Profile 2 might be a suitable tool for
      nasopharyngeal carcinoma screening. Cancer Prev Res; 10(9); 542-50. (c)2017 AACR.

PMID- 28754666
TI  - Mutations in BAG3 cause adult-onset Charcot-Marie-Tooth disease.

PMID- 28754664
TI  - Identification of a Human Airway Epithelial Cell Subpopulation with Altered
      Biophysical, Molecular, and Metastatic Properties.
AB  - Lung cancers are documented to have remarkable intratumoral genetic
      heterogeneity. However, little is known about the heterogeneity of biophysical
      properties, such as cell motility, and its relationship to early disease
      pathogenesis and micrometastatic dissemination. In this study, we identified and
      selected a subpopulation of highly migratory premalignant airway epithelial cells
      that were observed to migrate through microscale constrictions at up to 100-fold
      the rate of the unselected immortalized epithelial cell lines. This enhanced
      migratory capacity was found to be Rac1-dependent and heritable, as evidenced by
      maintenance of the phenotype through multiple cell divisions continuing more than
      8 weeks after selection. The morphology of this lung epithelial subpopulation was
      characterized by increased cell protrusion intensity. In a murine model of
      micrometastatic seeding and pulmonary colonization, the motility-selected
      premalignant cells exhibit both enhanced survival in short-term assays and
      enhanced outgrowth of premalignant lesions in longer-term assays, thus overcoming
      important aspects of "metastatic inefficiency." Overall, our findings indicate
      that among immortalized premalignant airway epithelial cell lines, subpopulations
      with heritable motility-related biophysical properties exist, and these may
      explain micrometastatic seeding occurring early in the pathogenesis of lung
      cancer. Understanding, targeting, and preventing these critical biophysical
      traits and their underlying molecular mechanisms may provide a new approach to
      prevent metastatic behavior. Cancer Prev Res; 10(9); 514-24. (c)2017 AACRSee
      related editorial by Hynds and Janes, p. 491.

PMID- 28754667
TI  - 'It's the progression, doctor': what patients with motor neurone disease really
      are interested in.

PMID- 28754668
TI  - Transglutaminase 2 Inhibition Reverses Mesenchymal Transdifferentiation of Glioma
      Stem Cells by Regulating C/EBPbeta Signaling.
AB  - Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor
      prognosis and resistance to conventional therapies. However, the molecular
      mechanisms underlying necrotic microenvironment-induced malignancy of GBM have
      not been elucidated. Here, we report that transglutaminase 2 (TGM2) is
      upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES)
      transdifferentiation of glioma stem cells (GSC) by regulating master
      transcription factors (TF), such as C/EBPbeta, TAZ, and STAT3. TGM2 expression
      was induced by macrophages/microglia-derived cytokines via NF-kappaB activation
      and further degraded DNA damage-inducible transcript 3 (GADD153) to induce
      C/EBPbeta expression, resulting in expression of the MES transcriptome.
      Downregulation of TGM2 decreased sphere-forming ability, tumor size, and
      radioresistance and survival in a xenograft mouse model through a loss of the MES
      signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and
      showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2
      expression was significantly increased in recurrent MES patients and inversely
      correlated with patient prognosis. Collectively, our results indicate that TGM2
      is a key molecular switch of necrosis-induced MES transdifferentiation and an
      important therapeutic target for MES GBM. Cancer Res; 77(18); 4973-84. (c)2017
      AACR.

PMID- 28754669
TI  - Integrating Models to Quantify Environment-Mediated Drug Resistance.
AB  - Drug resistance is the single most important driver of cancer treatment failure
      for modern targeted therapies, and the dialog between tumor and stroma has been
      shown to modulate the response to molecularly targeted therapies through
      proliferative and survival signaling. In this work, we investigate interactions
      between a growing tumor and its surrounding stroma and their role in facilitating
      the emergence of drug resistance. We used mathematical modeling as a theoretical
      framework to bridge between experimental models and scales, with the aim of
      separating intrinsic and extrinsic components of resistance in BRAF-mutated
      melanoma; the model describes tumor-stroma dynamics both with and without
      treatment. Integration of experimental data into our model revealed significant
      variation in either the intensity of stromal promotion or intrinsic tissue
      carrying capacity across animal replicates. Cancer Res; 77(19); 5409-18. (c)2017
      AACR.

PMID- 28754670
TI  - Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of
      Lkb1-Deficient Lung Adenocarcinoma.
AB  - Cells lacking the tumor suppressor gene LKB1/STK11 alter their metabolism to
      match the demands of accelerated growth, leaving them highly vulnerable to
      stress. However, targeted therapy for LKB1-deficient cancers has yet to be
      reported. In both Kras/p53/Lkb1 cell lines and a genetically engineered mouse
      model of Kras/p53/Lkb1-induced lung cancer, much higher rates of DNA damage
      occur, resulting in increased dependence on Chk1 checkpoint function. Here we
      demonstrate that short-term treatment with the Chk1 inhibitor AZD7762 reduces
      metabolism in pembrolizumab tumors, synergizing with the DNA-damaging drug
      gemcitabine to reduce tumor size in these models. Our results offer preclinical
      proof of concept for use of a Chk1 inhibitor to safely enhance the efficacy of
      gemcitabine, particularly in aggressive KRAS-driven LKB1-deficient lung
      adenocarcinomas. Cancer Res; 77(18); 5068-76. (c)2017 AACR.

PMID- 28754671
TI  - Src Inhibits the Hippo Tumor Suppressor Pathway through Tyrosine Phosphorylation
      of Lats1.
AB  - The Hippo pathway regulates cell proliferation, apoptosis, and stem cell self
      renewal, and its inactivation in animal models causes organ enlargement followed
      by tumorigenesis. Hippo pathway deregulation occurs in many human cancers, but
      the underlying mechanisms are not fully understood. Here, we report tyrosine
      phosphorylation of the Hippo pathway tumor suppressor LATS1 as a mechanism
      underlying its regulation by cell adhesion. A tyrosine kinase library screen
      identified Src as the kinase to directly phosphorylate LATS1 on multiple
      residues, causing attenuated Mob kinase activator binding and structural
      alteration of the substrate-binding pocket in the kinase domain. Cell matrix
      adhesion activated the Hippo pathway effector transcription coactivator YAP
      partially through Src-mediated phosphorylation and inhibition of LATS1. Aberrant
      Src activation abolished the tumor suppressor activity of LATS1 and induced
      tumorigenesis in a YAP-dependent manner. Protein levels of Src in human breast
      cancer tissues correlated with accumulation of active YAP dephosphorylated on the
      LATS1 target site. These findings reveal tyrosine phosphorylation of LATS1 by Src
      as a novel mechanism of Hippo pathway regulation by cell adhesion and suggest Src
      activation as an underlying reason for YAP deregulation in tumorigenesis. Cancer
      Res; 77(18); 4868-80. (c)2017 AACR.

PMID- 28754672
TI  - Spi-B-Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer
      Cells from Primary Tumors.
AB  - Dissociation from epithelial sheets and invasion through the surrounding stroma
      are critical early events during epithelial cancer metastasis. Here we find that
      a lymphocyte lineage-restricted transcription factor, Spi-B, is frequently
      expressed in human lung cancer tissues. The Spi-B-expressing cancer cells
      coexpressed vimentin but repressed E-cadherin and exhibited invasive behavior.
      Increased Spi-B expression was associated with tumor grade, lymphatic metastasis,
      and short overall survival. Mechanistically, Spi-B disrupted intercellular
      junctions and enhanced invasiveness by reconfiguring the chromatin structure of
      the tight junction gene claudin-2 (CLDN2) and repressing its transcription. These
      data suggest that Spi-B participates in mesenchymal invasion, linking epithelial
      cancer metastasis with a lymphatic transcriptional program. Cancer Res; 77(18);
      4809-22. (c)2017 AACR.

PMID- 28754673
TI  - Androgen Receptor Variants Mediate DNA Repair after Prostate Cancer Irradiation.
AB  - In prostate cancer, androgen deprivation therapy (ADT) enhances the cytotoxic
      effects of radiotherapy. This effect is associated with weakening of the DNA
      damage response (DDR) normally supported by the androgen receptor. As a
      significant number of patients will fail combined ADT and radiotherapy, we
      hypothesized that DDR may be driven by androgen receptor splice variants (ARV)
      induced by ADT. Investigating this hypothesis, we found that ARVs increase the
      clonogenic survival of prostate cancer cells after irradiation in an ADT
      independent manner. Notably, prostate cancer cell irradiation triggers binding of
      ARV to the catalytic subunit of the critical DNA repair kinase DNA-PK.
      Pharmacologic inhibition of DNA-PKc blocked this interaction, increased DNA
      damage, and elevated prostate cancer cell death after irradiation. Our findings
      provide a mechanistic rationale for therapeutic targeting of DNA-PK in the
      context of combined ADT and radiotherapy as a strategy to radiosensitize
      clinically localized prostate cancer. Cancer Res; 77(18); 4745-54. (c)2017 AACR.

PMID- 28754674
TI  - Adipose Progenitor Cell Secretion of GM-CSF and MMP9 Promotes a Stromal and
      Immunological Microenvironment That Supports Breast Cancer Progression.
AB  - A cell population with progenitor-like phenotype (CD45-CD34+) resident in human
      white adipose tissue (WAT) is known to promote the progression of local and
      metastatic breast cancer and angiogenesis. However, the molecular mechanisms of
      the interaction have not been elucidated. In this study, we identified two
      proteins that were significantly upregulated in WAT-derived progenitors after
      coculture with breast cancer: granulocyte macrophage colony-stimulating factor
      (GM-CSF) and matrix metallopeptidase 9 (MMP9). These proteins were released by
      WAT progenitors in xenograft and transgenic breast cancer models. GM-CSF was
      identified as an upstream modulator. Breast cancer-derived GM-CSF induced GM-CSF
      and MMP9 release from WAT progenitors, and GM-CSF knockdown in breast cancer
      cells neutralized the protumorigenic activity of WAT progenitors in preclinical
      models. GM-CSF neutralization in diet-induced obese mice significantly reduced
      immunosuppression, intratumor vascularization, and local and metastatic breast
      cancer progression. Similarly, MMP9 inhibition reduced neoplastic angiogenesis
      and significantly decreased local and metastatic tumor growth. Combined GM-CSF
      neutralization and MMP9 inhibition synergistically reduced angiogenesis and tumor
      progression. High-dose metformin inhibited GM-CSF and MMP9 release from WAT
      progenitors in in vitro and xenograft models. In obese syngeneic mice, metformin
      treatment mimicked the effects observed with GM-CSF neutralization and MMP9
      inhibition, suggesting these proteins as new targets for metformin. These
      findings support the hypothesis that GM-CSF and MMP9 promote the protumorigenic
      effect of WAT progenitors on local and metastatic breast cancer. Cancer Res;
      77(18); 5169-82. (c)2017 AACR.

PMID- 28754675
TI  - Connecting Cancer to Its Causes Requires Incorporation of Effects on Tissue
      Microenvironments.
AB  - In a recent article in Science, Tomasetti and colleagues present an expanded
      model for cancer risk, which they claim demonstrates the relative contribution of
      mutations caused by replication errors, environment, and heredity. The foundation
      of this model is the theory that the overwhelming driver of cancer risk is
      mutations. This perspective will present experimental evidence and evolutionary
      theory to challenge the basis of this underlying theory. An argument will be
      presented that the mutation-centric model of cancer suggests unrealistic
      solutions to cancer and distracts the research community from more promising
      approaches that consider tissue context. Cancer Res; 77(22); 6065-8. (c)2017
      AACR.

PMID- 28754676
TI  - NSD1 Inactivation and SETD2 Mutation Drive a Convergence toward Loss of Function
      of H3K36 Writers in Clear Cell Renal Cell Carcinomas.
AB  - Extensive dysregulation of chromatin-modifying genes in clear cell renal cell
      carcinoma (ccRCC) has been uncovered through next-generation sequencing. However,
      a scientific understanding of the cross-talk between epigenetic and genomic
      aberrations remains limited. Here we identify three ccRCC epigenetic clusters,
      including a clear cell CpG island methylator phenotype (C-CIMP) subgroup
      associated with promoter methylation of VEGF genes (FLT4, FLT1, and KDR). C-CIMP
      was furthermore characterized by silencing of genes related to vasculature
      development. Through an integrative analysis, we discovered frequent silencing of
      the histone H3 K36 methyltransferase NSD1 as the sole chromatin-modifying gene
      silenced by DNA methylation in ccRCC. Notably, tumors harboring NSD1 methylation
      were of higher grade and stage in different ccRCC datasets. NSD1 promoter
      methylation correlated with SETD2 somatic mutations across and within spatially
      distinct regions of primary ccRCC tumors. ccRCC harboring epigenetic silencing of
      NSD1 displayed a specific genome-wide methylome signature consistent with the
      NSD1 mutation methylome signature observed in Sotos syndrome. Thus, we concluded
      that epigenetic silencing of genes involved in angiogenesis is a hallmark of the
      methylator phenotype in ccRCC, implying a convergence toward loss of function of
      epigenetic writers of the H3K36 histone mark as a root feature of aggressive
      ccRCC. Cancer Res; 77(18); 4835-45. (c)2017 AACR.

PMID- 28754677
TI  - Access to care is not equal.

PMID- 28754678
TI  - Control of Regulatory T Cell Differentiation by the Transcription Factors Thpok
      and LRF.
AB  - The CD4+ lineage-specific transcription factor Thpok is required for intrathymic
      CD4+ T cell differentiation and, together with its homolog LRF, supports CD4+ T
      cell helper effector responses. However, it is not known whether these factors
      are needed for the regulatory T cell (Treg) arm of MHC class II responses. In
      this study, by inactivating in mice the genes encoding both factors in
      differentiated Tregs, we show that Thpok and LRF are redundantly required to
      maintain the size and functions of the postthymic Treg pool. They support IL-2
      mediated gene expression and the functions of the Treg-specific factor Foxp3.
      Accordingly, Treg-specific disruption of Thpok and Lrf causes a lethal
      inflammatory syndrome similar to that resulting from Treg deficiency. Unlike in
      conventional T cells, Thpok and LRF functions in Tregs are not mediated by their
      repression of the transcription factor Runx3. Additionally, we found that Thpok
      is needed for the differentiation of thymic Treg precursors, an observation in
      line with the fact that Foxp3+ Tregs are CD4+ cells. Thus, a common Thpok-LRF
      node supports both helper and regulatory arms of MHC class II responses.

PMID- 28754679
TI  - Adaptive from Innate: Human IFN-gamma+CD4+ T Cells Can Arise Directly from CXCL8
      Producing Recent Thymic Emigrants in Babies and Adults.
AB  - We recently demonstrated that the major effector function of neonatal CD4+ T
      cells is to produce CXCL8, a prototypic cytokine of innate immune cells. In this
      article, we show that CXCL8 expression, prior to proliferation, is common in
      newly arising T cells (so-called "recent thymic emigrants") in adults, as well as
      in babies. This effector potential is acquired in the human thymus, prior to TCR
      signaling, but rather than describing end-stage differentiation, such cells,
      whether isolated from neonates or adults, can further differentiate into IFN
      gamma-producing CD4+ T cells. Thus, the temporal transition of host defense from
      innate to adaptive immunity is unexpectedly mirrored at the cellular level by the
      capacity of human innate-like CXCL8-producing CD4+ T cells to transition directly
      into Th1 cells.

PMID- 28754680
TI  - Versican-Derived Matrikines Regulate Batf3-Dendritic Cell Differentiation and
      Promote T Cell Infiltration in Colorectal Cancer.
AB  - Colorectal cancer originates within immunologically complex microenvironments. To
      date, the benefits of immunotherapy have been modest, except in neoantigen-laden
      mismatch repair-deficient tumors. Approaches to enhance tumor-infiltrating
      lymphocytes in the tumor bed may substantially augment clinical immunotherapy
      responses. In this article, we report that proteolysis of the tolerogenic matrix
      proteoglycan versican (VCAN) strongly correlated with CD8+ T cell infiltration in
      colorectal cancer, regardless of mismatch repair status. Tumors displaying active
      VCAN proteolysis and low total VCAN were associated with robust (10-fold) CD8+ T
      cell infiltration. Tumor-intrinsic WNT pathway activation was associated with
      CD8+ T cell exclusion and VCAN accumulation. In addition to regulating VCAN
      levels at the tumor site, VCAN proteolysis results in the generation of bioactive
      fragments with novel functions (VCAN-derived matrikines). Versikine, a VCAN
      derived matrikine, enhanced the generation of CD103+CD11chiMHCIIhi conventional
      dendritic cells (cDCs) from Flt3L-mobilized primary bone marrow-derived
      progenitors, suggesting that VCAN proteolysis may promote differentiation of
      tumor-seeding DC precursors toward IRF8- and BATF3-expressing cDCs. Intratumoral
      BATF3-dependent DCs are critical determinants for T cell antitumor immunity,
      effector T cell trafficking to the tumor site, and response to immunotherapies.
      Our findings provide a rationale for testing VCAN proteolysis as a predictive
      and/or prognostic immune biomarker and VCAN-derived matrikines as novel
      immunotherapy agents.

PMID- 28754681
TI  - Nitric Oxide Modulates Macrophage Responses to Mycobacterium tuberculosis
      Infection through Activation of HIF-1alpha and Repression of NF-kappaB.
AB  - IFN-gamma is essential for control of Mycobacterium tuberculosis infection in
      vitro and in vivo. However, the mechanisms by which IFN-gamma controls infection
      remain only partially understood. One of the crucial IFN-gamma target genes
      required for control of M. tuberculosis is inducible NO synthase (iNOS). Although
      NO produced by iNOS is thought to have direct bactericidal activity against M.
      tuberculosis, the role of NO as a signaling molecule has been poorly
      characterized in the context M. tuberculosis infection. In this study, we found
      that iNOS broadly regulates the macrophage transcriptome during M. tuberculosis
      infection, activating antimicrobial pathways while also limiting inflammatory
      cytokine production. The transcription factor hypoxia inducible factor-1alpha
      (HIF-1alpha) was recently shown to be critical for IFN-gamma-mediated control of
      M. tuberculosis infection. We found that HIF-1alpha function requires NO
      production, and that HIF-1alpha and iNOS are linked by a positive feedback loop
      that amplifies macrophage activation. Furthermore, we found that NO inhibits NF
      kappaB activity to prevent hyperinflammatory responses. Thus, NO activates robust
      microbicidal programs while also limiting damaging inflammation. IFN-gamma
      signaling must carefully calibrate an effective immune response that does not
      cause excessive tissue damage, and this study identifies NO as a key player in
      establishing this balance during M. tuberculosis infection.

PMID- 28754682
TI  - Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic
      Pulmonary Fibrosis.
AB  - Autoimmunity has been implicated in the pathogenesis of idiopathic pulmonary
      fibrosis (IPF); however, the repertoire of autoantigens involved in this disease
      and the clinical relevance of these autoimmune responses are still being
      explored. Our initial discovery assays demonstrated that circulating and
      intrapulmonary vimentin levels are increased in IPF patients. Subsequent studies
      showed native vimentin induced HLA-DR-dependent in vitro proliferation of CD4 T
      cells from IPF patients and enhanced the production of IL-4, IL-17, and TGF-beta1
      by these lymphocytes in contrast to normal control specimens. Vimentin
      supplementation of IPF PBMC cultures also resulted in HLA-DR-dependent production
      of IgG with anti-vimentin specificities. Circulating anti-vimentin IgG
      autoantibody levels were much greater in IPF subjects from the University of
      Alabama at Birmingham (n = 102) and the University of Pittsburgh (U. Pitt., n =
      70) than in normal controls. Anti-vimentin autoantibody levels in IPF patients
      were HLA biased and inversely correlated with physiological measurements of lung
      function (i.e., forced expiratory volumes and diffusing capacities). Despite
      considerable intergroup differences in transplant-free survival between these two
      independent IPF cohorts, serious adverse outcomes were most frequent among the
      patients within each population that had the highest anti-vimentin autoantibody
      levels (University of Alabama at Birmingham: hazard ratio 2.5, 95% confidence
      interval 1.2-5.3, p = 0.012; University of Pittsburgh: hazard ratio 2.7, 95%
      confidence interval 1.3-5.5, p = 0.006). These data show that anti-vimentin
      autoreactivity is prevalent in IPF patients and is strongly associated with
      disease manifestations. These findings have implications with regard to the
      pathogenesis of this enigmatic disease and raise the possibility that therapies
      specifically directed at these autoimmune processes could have therapeutic
      efficacy.

PMID- 28754683
TI  - DARC extracellular domain remodeling in maturating reticulocytes explains
      Plasmodium vivax tropism.
AB  - Plasmodium vivax is the most prevalent parasite species that causes malaria in
      humans and exclusively infects reticulocytes. Reticulocyte infection is
      facilitated by P vivax Duffy binding protein (DBP), which utilizes DARC (Duffy
      antigen receptor for chemokines) as an entry point. However, the selective
      tropism of P vivax for transferrin receptor (CD71)-positive reticulocytes
      remained unexplained, given the constitutive expression of DARC during
      reticulocyte maturation. CD71/RNA double staining of reticulocytes enriched from
      adult peripheral blood reveals 4 distinct reticulocyte populations:
      CD71high/RNAhigh (~0.016%), CD71low/RNAhigh (~0.059%), CD71neg/RNAhigh (~0.37%),
      CD71neg/RNAlow (~0.55%), and erythrocytes CD71neg/RNAneg (~99%). We hypothesized
      that selective association of DBP with a small population of immature
      reticulocytes could explain the preference of P vivax for reticulocytes. Binding
      of specific monoclonal anti-DARC antibodies and recombinant DBP to
      CD71high/RNAhigh reticulocytes was significantly higher compared with other
      reticulocyte populations and erythrocytes. Interestingly, the total DARC protein
      throughout reticulocyte maturation was constant. The data suggest that selective
      exposure of the DBP binding site within DARC is key to the preferential binding
      of DBP to immature reticulocytes, which is the potential mechanism underlying the
      preferential infection of a reticulocyte subset by P vivax.

PMID- 28754684
TI  - Response: Making "perfect" the enemy of good.

PMID- 28754685
TI  - Engineering mammalian cells to seek senescence-associated secretory phenotypes.
AB  - Since the removal of senescent cells in model organisms has been linked to
      rejuvenation and increased lifespan, senotherapies have emerged to target
      senescent cells for death. In particular, interleukin-6 (IL6) is a prominent
      senescence-associated secretory phenotype (SASP) and, thus, seeking IL6 could
      potentially localize engineered cells to senescent cells for therapeutic
      intervention. Here, we engineered a chimeric IL6 receptor (IL6Rchi) that
      generates a Ca2+ signal in response to IL6 stimulation. When IL6Rchi was co
      expressed with an engineered Ca2+-activated RhoA (CaRQ), it enabled directed
      migration to IL6 in cells that have no such natural ability. Next, the removal of
      target cells was accomplished by the mechanism of membrane fusion and subsequent
      death. This work represents a first step towards engineering a cell to target
      senescent cells that secrete high levels of IL6. For increased specificity to
      senescent cells, it will likely be necessary for an engineered cell to recognize
      multiple SASPs simultaneously.

PMID- 28754686
TI  - L-leucyl-L-leucine methyl ester does not release cysteine cathepsins to the
      cytosol but inactivates them in transiently permeabilized lysosomes.
AB  - L-leucyl-L-leucine methyl ester (LLOMe) induces apoptosis, which is thought to be
      mediated by release of lysosomal cysteine cathepsins from permeabilized lysosomes
      into the cytosol. Here, we demonstrated in HeLa cells that apoptotic as well as
      sub-apoptotic concentrations of LLOMe caused rapid and complete lysosomal
      membrane permeabilization (LMP), as evidenced by loss of the proton gradient and
      release into the cytosol of internalized lysosomal markers below a relative
      molecular mass of 10,000. However, there was no evidence for the release of
      cysteine cathepsins B and L into the cytosol; rather they remained within
      lysosomes, where they were rapidly inactivated and degraded. LLOMe-induced
      adverse effects, including LMP, loss of cysteine cathepsin activity, caspase
      activation and cell death could be reduced by inhibition of cathepsin C, but not
      by inhibiting cathepsins B and L. When incubated with sub-apoptotic LLOMe
      concentrations, lysosomes transiently lost protons but annealed and re-acidified
      within hours. Full lysosomal function required new protein synthesis of cysteine
      cathepsins and other hydrolyses. Our data argue against the release of lysosomal
      enzymes into the cytosol and their proposed proteolytic signaling during LLOMe
      induced apoptosis.

PMID- 28754687
TI  - Cells lay their own tracks - optogenetic Cdc42 activation stimulates fibronectin
      deposition supporting directed migration.
AB  - Rho GTPase family members are known regulators of directed migration and
      therefore play key roles in processes including development, the immune response
      and cancer metastasis. However, their individual contributions to these processes
      are complex. Here, we modify the activity of the two Rho GTPase family members
      Rac and Cdc42 by optogenetically recruiting specific guanine nucleotide exchange
      factor (GEF) DH or PH domains to defined regions of the cell membrane. We find
      that the localized activation of both GTPases produces lamellipodia in cells
      plated on a fibronectin substrate. By using a novel optotaxis assay, we show that
      biased activation can drive directional migration. Interestingly, in the absence
      of exogenous fibronectin, Rac activation is insufficient to produce stable
      lamellipodia or directional migration whereas Cdc42 activation is sufficient for
      these processes. We find that a remarkably small amount of fibronectin (<10
      puncta per protrusion) is necessary to support stable GTPase-driven lamellipodia
      formation. Cdc42 bypasses the need for exogenous fibronectin by stimulating
      cellular fibronectin deposition under the newly formed lamellipodia.This article
      has an associated First Person interview with the first author of the paper.

PMID- 28754688
TI  - TRIM65 triggers beta-catenin signaling via ubiquitylation of Axin1 to promote
      hepatocellular carcinoma.
AB  - Deregulation of ubiquitin ligases contributes to the malignant progression of
      human cancers. Tripartite motif-containing protein 65 (TRIM65) is an E3 ubiquitin
      ligase and has been implicated in human diseases, but its role and clinical
      significance in hepatocellular carcinoma (HCC) remain unknown. Here, we showed
      that TRIM65 expression was increased in HCC tissues and associated with poor
      outcome in two independent cohorts containing 888 patients. In vitro and in vivo
      data demonstrated that overexpression of TRIM65 promoted cell growth and tumor
      metastasis, whereas knockdown of TRIM65 resulted in opposite phenotypes. Further
      studies revealed that TRIM65 exerted oncogenic activities via ubiquitylation of
      Axin1 to activate the beta-catenin signaling pathway. TRIM65 directly bound to
      Axin1 and accelerated its degradation through ubiquitylation. Furthermore, HMGA1
      was identified as an upstream regulator of TRIM65 in HCC cells. In clinical
      samples, TRIM65 expression was positively correlated with the expression of HMGA1
      and nuclear beta-catenin. Collectively, our data indicate that TRIM65 functions
      as an oncogene in HCC. The newly identified HMGA1/TRIM65/beta-catenin axis serves
      as a promising prognostic factor and therapeutic target.

PMID- 28754690
TI  - Too few people have access to tests and treatment for hepatitis, says WHO.

PMID- 28754689
TI  - Ezrin directly interacts with AQP2 and promotes its endocytosis.
AB  - The water channel aquaporin-2 (AQP2) is a major regulator of water homeostasis in
      response to vasopressin (VP). Dynamic trafficking of AQP2 relies on its close
      interaction with trafficking machinery proteins and the actin cytoskeleton. Here,
      we report the identification of ezrin, an actin-binding protein from the
      ezrin/radixin/moesin (ERM) family as an AQP2-interacting protein. Ezrin was first
      detected in a co-immunoprecipitation (co-IP) complex using an anti-AQP2 antibody
      in a proteomic analysis. Immunofluorescence staining revealed the co-expression
      of ezrin and AQP2 in collecting duct principal cells, and VP treatment caused
      redistribution of both proteins to the apical membrane. The ezrin-AQP2
      interaction was confirmed by co-IP experiments with an anti-ezrin antibody, and
      by pulldown assays using purified full-length and FERM domain-containing
      recombinant ezrin. By using purified recombinant proteins, we showed that ezrin
      directly interacts with AQP2 C-terminus through its N-terminal FERM domain.
      Knocking down ezrin expression with shRNA resulted in increased membrane
      accumulation of AQP2 and reduced AQP2 endocytosis. Therefore, through direct
      interaction with AQP2, ezrin facilitates AQP2 endocytosis, thus linking the
      dynamic actin cytoskeleton network with AQP2 trafficking.

PMID- 28754691
TI  - The Hsp70 interdomain linker is a dynamic switch that enables allosteric
      communication between two structured domains.
AB  - Hsp70 molecular chaperones play key roles in cellular protein homeostasis by
      binding to exposed hydrophobic regions of incompletely folded or aggregated
      proteins. This crucial Hsp70 function relies on allosteric communication between
      two well-structured domains: an N-terminal nucleotide-binding domain (NBD) and a
      C-terminal substrate-binding domain (SBD), which are tethered by an interdomain
      linker. ATP or ADP binding to the NBD alters the substrate-binding affinity of
      the SBD, triggering functionally essential cycles of substrate binding and
      release. The interdomain linker is a well-structured participant in the
      interdomain interface in ATP-bound Hsp70s. By contrast, in the ADP-bound state,
      exemplified by the Escherichia coli Hsp70 DnaK, the interdomain linker is
      flexible. Hsp70 interdomain linker sequences are highly conserved; moreover,
      mutations in this region compromise interdomain allostery. To better understand
      the role of this region in Hsp70 allostery, we used molecular dynamics
      simulations to explore the conformational landscape of the interdomain linker in
      ADP-bound DnaK and supported our simulations by strategic experimental data. We
      found that while the interdomain linker samples many conformations, it behaves as
      three relatively ordered segments connected by hinges. As a consequence, the
      distances and orientations between the NBD and SBD are limited. Additionally, the
      C-terminal region of the linker forms previously unreported, transient
      interactions with the SBD, and the predominant linker-docking site is available
      in only one allosteric state, that with high affinity for substrate. This
      preferential binding implicates the interdomain linker as a dynamic allosteric
      switch. The linker-binding site on the SBD is a potential target for small
      molecule modulators of the Hsp70 allosteric cycle.

PMID- 28754692
TI  - An in vitro tag-and-modify protein sample generation method for single-molecule
      fluorescence resonance energy transfer.
AB  - Biomolecular systems exhibit many dynamic and biologically relevant properties,
      such as conformational fluctuations, multistep catalysis, transient interactions,
      folding, and allosteric structural transitions. These properties are challenging
      to detect and engineer using standard ensemble-based techniques. To address this
      drawback, single-molecule methods offer a way to access conformational
      distributions, transient states, and asynchronous dynamics inaccessible to these
      standard techniques. Fluorescence-based single-molecule approaches are
      parallelizable and compatible with multiplexed detection; to date, however, they
      have remained limited to serial screens of small protein libraries. This stems
      from the current absence of methods for generating either individual dual-labeled
      protein samples at high throughputs or protein libraries compatible with
      multiplexed screening platforms. Here, we demonstrate that by combining purified
      and reconstituted in vitro translation, quantitative unnatural amino acid
      incorporation via AUG codon reassignment, and copper-catalyzed azide-alkyne
      cycloaddition, we can overcome these challenges for target proteins that are, or
      can be, methionine-depleted. We present an in vitro parallelizable approach that
      does not require laborious target-specific purification to generate dual-labeled
      proteins and ribosome-nascent chain libraries suitable for single-molecule FRET
      based conformational phenotyping. We demonstrate the power of this approach by
      tracking the effects of mutations, C-terminal extensions, and ribosomal tethering
      on the structure and stability of three protein model systems: barnase, spectrin,
      and T4 lysozyme. Importantly, dual-labeled ribosome-nascent chain libraries
      enable single-molecule co-localization of genotypes with phenotypes, are well
      suited for multiplexed single-molecule screening of protein libraries, and should
      enable the in vitro directed evolution of proteins with designer single-molecule
      conformational phenotypes of interest.

PMID- 28754693
TI  - Funiculosin variants and phosphorylated derivatives promote innate immune
      responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex.
AB  - The Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2) complex
      is essential for LPS recognition and induces innate immune responses against Gram
      negative bacteria. As activation of TLR4/MD-2 is also critical for the induction
      of adaptive immune responses, TLR4/MD-2 agonists have been developed as vaccine
      adjuvants, but their efficacy has not yet been ascertained. Here, we demonstrate
      that a funiculosin (FNC) variant, FNC-RED, and FNC-RED and FNC derivatives are
      agonists for both murine and human TLR4/MD-2. FNC-RED induced nuclear factor
      kappaB (NF-kappaB) activation via murine TLR4/MD-2, whereas FNC had no TLR4/MD-2
      stimulatory activity. Biacore analysis revealed that FNC-RED binds to murine
      TLR4/MD-2 but not murine radioprotective 105 (RP105)/myeloid differentiation
      factor-1 (MD-1), another LPS sensor. FNC-RED induced CD14-independent expressions
      of pro-inflammatory cytokines and co-stimulatory molecules in murine macrophages
      and dendritic cells. In contrast, FNC-RED stimulation was reduced in CD14
      dependent LPS responses, including dimerization and internalization of TLR4/MD-2
      and IFN-beta expression. FNC-RED-induced IL-12p40 production from murine
      dendritic cells was dependent on NF-kappaB but not MAPK pathway. In addition,
      fetal bovine serum augmented lipid A-induced NF-kappaB activation but blocked FNC
      RED-mediated responses. Two synthetic phosphate group-containing FNC-RED and FNC
      derivatives, FNC-RED-P01 and FNC-P01, respectively, activated human TLR4/MD-2,
      unlike FNC-RED. Finally, computational analysis revealed that this species
      specific activation by FNC-RED and FNC-RED-P01 resulted from differences in
      electrostatic surface potentials between murine and human TLR4/MD-2. We conclude
      that FNC-RED and its synthetic derivative represent a novel category of murine
      and human TLR4/MD-2 agonist.

PMID- 28754695
TI  - Eastern equine encephalitis.
AB  - We describe a patient who died from a fulminant presentation of encephalitis.
      After an exhaustive search, we found no treatable cause. Postmortem PCR analysis
      of brain tissue led to a diagnosis of eastern equine encephalitis. We have
      identified several clinical pearls that may assist others in making the diagnosis
      earlier in the disease course.

PMID- 28754694
TI  - Remodeling of ER-exit sites initiates a membrane supply pathway for autophagosome
      biogenesis.
AB  - Autophagosomes are double-membrane vesicles generated during autophagy.
      Biogenesis of the autophagosome requires membrane acquisition from intracellular
      compartments, the mechanisms of which are unclear. We previously found that a
      relocation of COPII machinery to the ER-Golgi intermediate compartment (ERGIC)
      generates ERGIC-derived COPII vesicles which serve as a membrane precursor for
      the lipidation of LC3, a key membrane component of the autophagosome. Here we
      employed super-resolution microscopy to show that starvation induces the
      enlargement of ER-exit sites (ERES) positive for the COPII activator, SEC12, and
      the remodeled ERES patches along the ERGIC A SEC12 binding protein, CTAGE5, is
      required for the enlargement of ERES, SEC12 relocation to the ERGIC, and
      modulates autophagosome biogenesis. Moreover, FIP200, a subunit of the ULK
      protein kinase complex, facilitates the starvation-induced enlargement of ERES
      independent of the other subunits of this complex and associates via its C
      terminal domain with SEC12. Our data indicate a pathway wherein FIP200 and CTAGE5
      facilitate starvation-induced remodeling of the ERES, a prerequisite for the
      production of COPII vesicles budded from the ERGIC that contribute to
      autophagosome formation.

PMID- 28754696
TI  - The war on US women's reproductive rights.

PMID- 28754697
TI  - Two thirds of unfilled consultant posts have no applicants, shows census.

PMID- 28754698
TI  - Plans for major NHS cuts are shrouded in secrecy, warns BMA.

PMID- 28754699
TI  - A germline deletion of 9p21.3 presenting as familial melanoma, astrocytoma and
      breast cancer: clinical and genetic counselling challenges.

PMID- 28754700
TI  - Segregation of mitochondrial DNA mutations in the human placenta: implication for
      prenatal diagnosis of mtDNA disorders.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) disorders have a high clinical variability,
      mainly explained by variation of the mutant load across tissues. The high
      recurrence risk of these serious diseases commonly results in requests from at
      risk couples for prenatal diagnosis (PND), based on determination of the mutant
      load on a chorionic villous sample (CVS). Such procedures are hampered by the
      lack of data regarding mtDNA segregation in the placenta.The objectives of this
      report were to determine whether mutant loads (1) are homogeneously distributed
      across the whole placentas, (2) correlate with those in amniocytes and cord blood
      cells and (3) correlate with the mtDNA copy number. METHODS: We collected 11
      whole placentas carrying various mtDNA mutations (m.3243A>G, m.8344A>G,
      m.8993T>G, m.9185T>C and m.10197G>A) and, when possible, corresponding amniotic
      fluid samples (AFSs) and cord blood samples. We measured mutant loads in multiple
      samples from each placenta (n= 6-37), amniocytes and cord blood cells, as well as
      total mtDNA content in placenta samples. RESULTS: Load distribution was
      homogeneous at the sample level when average mutant load was low (<20%) or high
      (>80%) at the whole placenta level. By contrast, a marked heterogeneity was
      observed (up to 43%) in the intermediate range (20%-80%), the closer it was to
      40%-50% the mutant load, the wider the distribution. Mutant loads were found to
      be similar in amniocytes and cord blood cells, at variance with placenta samples.
      mtDNA content correlated to mutant load in m.3243A>G placentas only. CONCLUSION:
      These data indicate that (1) mutant load determined from CVS has to be
      interpreted with caution for PND of some mtDNA disorders and should be associated
      with/substituted by a mutant load measurement on amniocytes; (2) the m.3243A>G
      mutation behaves differently from other mtDNA mutations with respect to the
      impact on mtDNA copy number, as previously shown in human preimplantation
      embryogenesis.

PMID- 28754701
TI  - Genome Sequence and Composition of a Tolyporphin-Producing Cyanobacterium
      Microbial Community.
AB  - The cyanobacterial culture HT-58-2 was originally described as a strain of
      Tolypothrix nodosa with the ability to produce tolyporphins, which comprise a
      family of distinct tetrapyrrole macrocycles with reported efflux pump inhibition
      properties. Upon reviving the culture from what was thought to be a nonextant
      collection, studies of culture conditions, strain characterization, phylogeny,
      and genomics have been undertaken. Here, HT-58-2 was shown by 16S rRNA analysis
      to closely align with Brasilonema strains and not with Tolypothrix isolates.
      Light, fluorescence, and scanning electron microscopy revealed cyanobacterium
      filaments that are decorated with attached bacteria and associated with free
      bacteria. Metagenomic surveys of HT-58-2 cultures revealed a diversity of
      bacteria dominated by Erythrobacteraceae, 97% of which are Porphyrobacter
      species. A dimethyl sulfoxide washing procedure was found to yield enriched
      cyanobacterial DNA (presumably by removing community bacteria) and sequence data
      sufficient for genome assembly. The finished, closed HT-58-2Cyano genome consists
      of 7.85 Mbp (42.6% G+C) and contains 6,581 genes. All genes for biosynthesis of
      tetrapyrroles (e.g., heme, chlorophyll a, and phycocyanobilin) and almost all for
      cobalamin were identified dispersed throughout the chromosome. Among the 6,177
      protein-encoding genes, coding sequences (CDSs) for all but two of the eight
      enzymes for conversion of glutamic acid to protoporphyrinogen IX also were found
      within one major gene cluster. The cluster also includes 10 putative genes (and
      one hypothetical gene) encoding proteins with domains for a glycosyltransferase,
      two cytochrome P450 enzymes, and a flavin adenine dinucleotide (FAD)-binding
      protein. The composition of the gene cluster suggests a possible role in
      tolyporphin biosynthesis.IMPORTANCE A worldwide search more than 25 years ago for
      cyanobacterial natural products with anticancer activity identified a culture (HT
      58-2) from Micronesia that produces tolyporphins. Tolyporphins are tetrapyrroles,
      like chlorophylls, but have several profound structural differences that reside
      outside the bounds of known biosynthetic pathways. To begin probing the
      biosynthetic origin and biological function of tolyporphins, our research has
      focused on studying the cyanobacterial strain, about which almost nothing has
      been previously reported. We find that the HT-58-2 culture is composed of the
      cyanobacterium and a community of associated bacteria, complicating the question
      of which organisms make tolyporphins. Elucidation of the cyanobacterial genome
      revealed an intriguing gene cluster that contains tetrapyrrole biosynthesis genes
      and a collection of unknown genes, suggesting that the cluster may be responsible
      for tolyporphin production. Knowledge of the genome and the gene cluster sharply
      focuses research to identify related cyanobacterial producers of tolyporphins and
      delineate the tolyporphin biosynthetic pathway.

PMID- 28754702
TI  - Mycobacterium abscessus Displays Fitness for Fomite Transmission.
AB  - Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterium (NTM)
      increasingly reported in soft tissue infections and chronic lung diseases,
      including cystic fibrosis. The environmental source of M. abscessus has not been
      definitively identified, but NTM have been detected in soil and water. To
      determine the potential of soil-derived M. abscessus as an infectious source, we
      explored the association, growth, and survival of M. abscessus with defined
      mineral particulates, including kaolin, halloysite, and silicone dioxide, and
      house dust as possible M. abscessus fomites. M. abscessus physically associated
      with particulates, and the growth of M. abscessus was enhanced in the presence of
      both kaolin and house dust. M. abscessus survived desiccation for 2 weeks but was
      not viable after 3 weeks. The rate of decline of M. abscessus viability during
      desiccation was reduced in the presence of house dust. The evidence for enhanced
      growth and survival of M. abscessus during alternating growth and drying periods
      suggests that dissemination could occur when in wet or dry environments. These
      studies are important to understand environmental survival and acquisition of
      NTM.IMPORTANCE The environmental source of pulmonary Mycobacterium abscessus
      infections is not known. Fomites are nonliving carriers of infectious agents and
      may contribute to acquisition of M. abscessus This study provides evidence that
      M. abscessus growth is enhanced in the presence of particulates, using kaolin, an
      abundant natural clay mineral, and house dust as experimental fomites. Moreover,
      M. abscessus survived desiccation for up to 2 weeks in the presence of house
      dust, kaolin, and several chemically defined mineral particulates; mycobacterial
      viability during extended periods of dessication was enhanced by the presence of
      house dust. The growth characteristics of M. abscessus with particulates suggest
      that a fomite mechanism of transmission may contribute to M. abscessus
      acquisition, which may lead to strategies to better control infections by M.
      abscessus and related organisms.

PMID- 28754703
TI  - Biosynthesis and evolution of coronafacoyl phytotoxin production in the common
      scab pathogen Streptomyces scabies.
AB  - Coronafacoyl phytotoxins are an important family of plant toxins that are
      produced by several different phytopathogenic bacteria, including the
      gammaproteobacterium Pseudomonas syringae and the actinobacterium Streptomyces
      scabies. The phytotoxins consist of coronafacic acid (CFA) linked via an amide
      bond to different amino acids or amino acid derivatives. Previous work suggested
      that S. scabies and P. syringae use distinct biosynthetic pathways for producing
      CFA, which is subsequently linked to its amino acid partner to form the complete
      phytotoxin. Here, we provide further evidence that the S. scabies CFA
      biosynthetic pathway is novel by characterizing the role of CYP107AK1, a
      predicted cytochrome P450 that has no homologue in P. syringae Deletion analysis
      of the CYP107AK1 gene abolished production of coronafacoyl-isoleucine (CFA-Ile),
      the primary coronafacoyl phytotoxin produced by S. scabies. Structural
      elucidation of accumulated biosynthetic intermediates in the DeltaCYP107AK1
      mutant indicated that CYP107AK1 is required for introducing the oxygen atom that
      ultimately forms the carbonyl group in the CFA backbone. The CYP107AK1 gene along
      with two additional genes involved in CFA-Ile biosynthesis in S. scabies were
      found associated with putative CFA biosynthetic genes in other actinobacteria but
      not in other organisms. Analysis of the overall genetic content and organization
      of known and putative CFA biosynthetic gene clusters, together with phylogenetic
      analysis of the core biosynthetic genes indicates that horizontal gene transfer
      has played an important role in the dissemination of the gene cluster, and that
      rearrangement, insertion and/or deletion events have likely contributed to the
      divergent biosynthetic evolution of coronafacoyl phytotoxins in
      bacteria.IMPORTANCE The ability of plants to defend themselves against invading
      pathogens relies on complex signalling pathways that are controlled by key
      phytohormones such as jasmonic acid (JA). Some phytopathogenic bacteria have
      evolved the ability to manipulate JA signalling in order to overcome host
      defenses by producing coronatine (COR), which functions as a potent JA mimic. COR
      and COR-like molecules, collectively referred to as coronafacoyl phytotoxins, are
      produced by several different plant pathogenic bacteria, and this study provides
      supporting evidence that different biosynthetic pathways are utilized by
      different bacteria for production of these phytotoxins. In addition, our study
      provides a greater understanding of how coronafacoyl phytotoxin biosynthesis may
      have evolved in phylogenetically distinct bacteria, and we demonstrate that
      production of these compounds may be more widespread than previously recognized
      and that their role for the producing organism may not be limited to host
      pathogen interactions.

PMID- 28754704
TI  - Metagenomic Analysis of Dairy Bacteriophages: Extraction Method and Pilot Study
      on Whey Samples Derived from Using Undefined and Defined Mesophilic Starter
      Cultures.
AB  - Despite being potentially highly useful for characterizing the biodiversity of
      phages, metagenomic studies are currently not available for dairy bacteriophages,
      partly due to the lack of a standard procedure for phage extraction. We optimized
      an extraction method that allows the removal of the bulk protein from whey and
      milk samples with losses of less than 50% of spiked phages. The protocol was
      applied to extract phages from whey in order to test the notion that members of
      Lactococcus lactis 936 (now Sk1virus), P335, c2 (now C2virus) and Leuconostoc
      phage groups are the most frequently encountered in the dairy environment. The
      relative abundance and diversity of phages in eight and four whey mixtures from
      dairies using undefined mesophilic mixed-strain cultures containing Lactococcus
      lactis subsp. lactis biovar diacetylactis and Leuconostoc species (i.e., DL
      starter cultures) and defined cultures, respectively, were assessed. Results
      obtained from transmission electron microscopy and high-throughput sequence
      analyses revealed the dominance of Lc. lactis 936 phages (order Caudovirales,
      family Siphoviridae) in dairies using undefined DL starter cultures and Lc.
      lactis c2 phages (order Caudovirales, family Siphoviridae) in dairies using
      defined cultures. The 936 and Leuconostoc phages demonstrated limited diversity.
      Possible coinduction of temperate P335 prophages and satellite phages in one of
      the whey mixtures was also observed.IMPORTANCE The method optimized in this study
      could provide an important basis for understanding the dynamics of the phage
      community (abundance, development, diversity, evolution, etc.) in dairies with
      different sizes, locations, and production strategies. It may also enable the
      discovery of previously unknown phages, which is crucial for the development of
      rapid molecular biology-based methods for phage burden surveillance systems. The
      dominance of only a few phage groups in the dairy environment signifies the depth
      of knowledge gained over the past decades, which served as the basis for
      designing current phage control strategies. The presence of a correlation between
      phages and the type of starter cultures being used in dairies might help to
      improve the selection and/or design of suitable, custom, and cost-efficient phage
      control strategies.

PMID- 28754705
TI  - In Vivo Roles of Fatty Acid Biosynthesis Enzymes in Biosynthesis of Biotin and
      alpha-Lipoic Acid in Corynebacterium glutamicum.
AB  - For fatty acid biosynthesis, Corynebacterium glutamicum uses two type I fatty
      acid synthases (FAS-I), FasA and FasB, in addition to acetyl-coenzyme A (CoA)
      carboxylase (ACC) consisting of AccBC, AccD1, and AccE. The in vivo roles of the
      enzymes in supplying precursors for biotin and alpha-lipoic acid remain unclear.
      Here, we report genetic evidence demonstrating that the biosynthesis of these
      cofactors is linked to fatty acid biosynthesis through the FAS-I pathway. For
      this study, we used wild-type C. glutamicum and its derived biotin vitamer
      producer BFI-5, which was engineered to express Escherichia coli bioBF and
      Bacillus subtilis bioI Disruption of either fasA or fasB in strain BFI-5 led to
      decreased production of biotin vitamers, whereas its amplification contributed to
      increased production, with a larger impact of fasA in both cases. Double
      disruptions of fasA and fasB resulted in no biotin vitamer production. The acc
      genes showed a positive effect on production when amplified simultaneously.
      Augmented fatty acid biosynthesis was also reflected in pimelic acid production
      when carbon flow was blocked at the BioF reaction. These results indicate that
      carbon flow down the FAS-I pathway is destined for channeling into the biotin
      biosynthesis pathway, and that FasA in particular has a significant impact on
      precursor supply. In contrast, fasB disruption resulted in auxotrophy for lipoic
      acid or its precursor octanoic acid in both wild-type and BFI-5 strains. The
      phenotypes were fully complemented by plasmid-mediated expression of fasB but not
      fasA These results reveal that FasB plays a specific physiological role in lipoic
      acid biosynthesis in C. glutamicumIMPORTANCE For the de novo biosynthesis of
      fatty acids, C. glutamicum exceptionally uses a eukaryotic multifunctional type I
      fatty acid synthase (FAS-I) system comprising FasA and FasB, in contrast to most
      bacteria, such as E. coli and B. subtilis, which use an individual nonaggregating
      type II fatty acid synthase (FAS-II) system. In this study, we reported genetic
      evidence demonstrating that the FAS-I system is the source of the biotin
      precursor in vivo in the engineered biotin-prototrophic C. glutamicum strain.
      This study also uncovered the important physiological role of FasB in lipoic acid
      biosynthesis. Here, we present an FAS-I enzyme that functions in supplying the
      lipoic acid precursor, although its biosynthesis has been believed to exclusively
      depend on FAS-II in organisms. The findings obtained here provide new insights
      into the metabolic engineering of this industrially important microorganism to
      produce these compounds effectively.

PMID- 28754706
TI  - Critical Knowledge Gaps in Our Understanding of Environmental Cycling and
      Transmission of Leptospira spp.
AB  - Exposure to soil or water contaminated with the urine of Leptospira-infected
      animals is the most common way in which humans contract leptospirosis. Entire
      populations can be at high risk of leptospirosis while working in inundated
      fields, when engaging in aquatic sports, or after periods of heavy rainfall. The
      risk of infection after contact with these environmental sources depends on the
      ability of Leptospira bacteria to survive, persist, and infect new hosts.
      Multiple variables such as soil and water pH, temperature, and even environmental
      microbial communities are likely to shape the environmental conditions needed by
      the pathogen to persist. Here we review what is known about the environmental
      phase of the infectious Leptospira transmission cycle and identify knowledge gaps
      that will serve as a guide for future research.

PMID- 28754707
TI  - Repression of Salmonella host cell invasion by aromatic small molecules from the
      human fecal metabolome.
AB  - The human microbiome is a collection of microorganisms that inhabit every surface
      of the body that is exposed to the environment, generally coexisting peacefully
      with their host. These microbes have important functions such as the production
      of vitamins, maturation of the immune system and protection against pathogens. We
      have previously shown that a small-molecule extract from the human fecal
      microbiome has a strong repressive effect on Salmonella enterica serovar
      Typhimurium host cell invasion by modulating the expression of genes involved in
      this process. Here, we describe the characterization of this biological activity.
      Using a series of purification methods, we obtained fractions with biological
      activity and characterized them by mass spectrometry. These experiments revealed
      an abundance of aromatic compounds in the bioactive fraction. Selected compounds
      were obtained from commercial sources and tested with respect to their ability to
      repress the expression of hilA, the gene encoding the master regulator of
      invasion genes in Salmonella We found that the aromatic compound 3,4
      dimethylbenzoic acid acts as a strong inhibitor of hilA expression as well as
      invasion of cultured host cells by Salmonella Future studies should reveal the
      molecular details of this phenomenon, such as the signaling cascades involved in
      sensing this bioactive molecule.Importance Microbes constantly sense and adapt to
      their environment. Often, this is achieved through the production and sensing of
      small extracellular molecules. The human body is colonized by complex communities
      of microbes, and, given their biological and chemical diversity, these ecosystems
      represent a platform where the production and sensing of molecules occurs. In
      previous work, we showed that small molecules produced by microbes from the human
      gut can significantly impair the virulence of the enteric pathogen Salmonella
      enterica Here, we describe a specific compound from the human gut that produces
      this same effect. The results from this work not only shed light on an important
      biological phenomenon occurring in our bodies but also may represent an
      opportunity to develop drugs that can target these small-molecule interactions to
      protect us from enteric infections and other diseases.

PMID- 28754708
TI  - Glucosylglycerate Phosphorylase, an Enzyme with Novel Specificity Involved in
      Compatible Solute Metabolism.
AB  - Family GH13_18 of the carbohydrate-active enzyme database consists of retaining
      glycoside phosphorylases that have attracted interest with their potential for
      synthesizing valuable alpha-sugars and glucosides. Sucrose phosphorylase was
      believed to be the only enzyme with specificity in this subfamily for many years,
      but recent work revealed an enzyme with a different function and hinted at an
      even broader diversity that is left to discover. In this study, a putative
      sucrose phosphorylase from Meiothermus silvanus that resides in a previously
      unexplored branch of the family's phylogenetic tree was expressed and
      characterized. Unexpectedly, no activity on sucrose was observed. Guided by a
      thorough inspection of the genomic landscape surrounding other genes in the
      branch, the enzyme was found to be a glucosylglycerate phosphorylase, with a
      specificity never before reported. Homology modeling, docking, and mutagenesis
      pinpointed particular acceptor site residues (Asn275 and Glu383) involved in the
      binding of glycerate. Various organisms known to synthesize and accumulate
      glucosylglycerate as a compatible solute possess a putative glucosylglycerate
      phosphorylase gene, indicating that the phosphorylase may be a regulator of its
      intracellular levels. Moreover, homologs of this novel enzyme appear to be
      distributed among diverse bacterial phyla, a finding which suggests that many
      more organisms may be capable of assimilating or synthesizing glucosylglycerate
      than previously assumed.IMPORTANCE Glycoside phosphorylases are an intriguing
      group of carbohydrate-active enzymes that have been used for the synthesis of
      various economically appealing glycosides and sugars, and they are frequently
      subjected to enzyme engineering to further expand their application potential.
      The novel specificity discovered in this work broadens the diversity of these
      phosphorylases and opens up new possibilities for the efficient production of
      glucosylglycerate, which is a remarkably potent and versatile stabilizer for
      protein formulations. Finally, it is a new piece of the puzzle of
      glucosylglycerate metabolism, being the only known enzyme capable of catalyzing
      the breakdown of glucosylglycerate in numerous bacterial phyla.

PMID- 28754710
TI  - US cancer groups call for more diverse populations to be included in trials.

PMID- 28754709
TI  - The Sortase-Dependent Fimbriome of the Genus Bifidobacterium: Extracellular
      Structures with Potential To Modulate Microbe-Host Dialogue.
AB  - Bifidobacteria are important gut commensals of mammals, including humans, of any
      age. However, the molecular mechanisms by which these microorganisms establish
      themselves in the mammalian gut and persist in this environment are largely
      unknown. Here, we analyzed the genetic diversity of the predicted arsenal of
      sortase-dependent pili of known and sequenced members of the Bifidobacterium
      genus and constructed a bifidobacterial sortase-dependent fimbriome database. Our
      analyses revealed considerable genetic variability of the sortase-dependent
      fimbriome among bifidobacterial (sub)species, which appears to have been due to
      horizontal gene transfer events and for which we were able to perform
      evolutionary mapping. Functional assessment by transcriptome analysis and binding
      assays involving different substrates demonstrates how bifidobacterial pili are
      pivotal in promoting various abilities for adhesion to glycans and extracellular
      matrix proteins, thereby supporting the ecological success of bifidobacteria in
      the mammalian gut.IMPORTANCE Adhesion of bifidobacterial cells to the mucosa of
      the large intestine is considered a hallmark for the persistence and colonization
      of these bacteria in the human gut. In this context, we analyzed the genetic
      diversity of the predicted arsenal of sortase-dependent pili of known and
      sequenced members of the Bifidobacterium genus, and constructed a bifidobacterial
      sortase-dependent fimbriome database. Our analyses revealed considerable genetic
      variability of the sortase-dependent fimbriome among bifidobacterial
      (sub)species, which appears to have been due to horizontal gene transfer events.
      In addition, functional assessment by transcriptome analysis and binding assays
      involving different substrates demonstrates how bifidobacterial pili are crucial
      in promoting various abilities for adhesion to glycans and extracellular matrix
      proteins, thereby supporting the ecological success of bifidobacteria in the
      mammalian gut. This study represents a complete genomic study regarding the
      presence of fimbriae in the genus Bifidobacterium.

PMID- 28754711
TI  - 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic
      acid bacteria, enhances energy metabolism by activation of TRPV1.
AB  - Gut microbiota can regulate the host energy metabolism; however, the underlying
      mechanisms that could involve gut microbiota-derived compounds remain to be
      understood. Therefore, in this study, we investigated the effects of KetoA [10
      oxo-12(Z)-octadecenoic acid]-a linoleic acid metabolite produced by gut lactic
      acid bacteria-on whole-body energy metabolism and found that dietary intake of
      KetoA could enhance energy expenditure in mice, thereby protecting mice from diet
      induced obesity. By using Ca2+ imaging and whole-cell patch-clamp methods, KetoA
      was noted to potently activate transient receptor potential vanilloid 1 (TRPV1)
      and enhance noradrenalin turnover in adipose tissues. In addition, KetoA up
      regulated genes that are related to brown adipocyte functions, including
      uncoupling protein 1 (UCP1) in white adipose tissue (WAT), which was later
      diminished in the presence of a beta-adrenoreceptor blocker. By using obese and
      diabetic model KK-Ay mice, we further show that KetoA intake ameliorated obesity
      associated metabolic disorders. In the absence of any observed KetoA-induced
      antiobesity effect or UCP1 up-regulation in TRPV1-deficient mice, we prove that
      the antiobesity effect of KetoA was caused by TRPV1 activation-mediated browning
      in WAT. KetoA produced in the gut could therefore be involved in the regulation
      of host energy metabolism.-Kim, M., Furuzono, T., Yamakuni, K., Li, Y., Kim, Y.
      I., Takahashi, H., Ohue-Kitano, R., Jheng, H.-F., Takahashi, N., Kano, Y., Yu,
      R., Kishino, S., Ogawa, J., Uchida, K., Yamazaki, J., Tominaga, M., Kawada, T.,
      Goto, T. 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by
      gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1.

PMID- 28754712
TI  - Engineered islet cell clusters transplanted into subcutaneous space are superior
      to pancreatic islets in diabetes.
AB  - An alternative route for pancreatic islet transplantation is the subcutaneous
      space; however, inadequate vascularization in the subcutaneous space limits the
      availability of oxygen and nutrients to the subcutaneously transplanted islets,
      which leads to the development of a necrotic core in the islets, thereby causing
      islet dysfunction. Thus, we aimed to prevent the early apoptosis of pancreatic
      islets after transplantation into subcutaneous space by preparing islet clusters
      of appropriate size. We prepared fully functional islet cell clusters (ICCs) by
      using the hanging-drop technique. We optimized the size of ICCs on the basis of
      viability and functionality after culture in an hypoxic environment. We
      transplanted ICCs into the subcutaneous space of diabetic mice and evaluated the
      viability of the islets at the transplantation site. In an hypoxic environment,
      ICCs exhibited improved viability and functionality compared with control islets.
      ICCs, upon transplantation into the hypoxic subcutaneous space of diabetic mice,
      showed better glycemic control compared with control islets. Live/dead imaging of
      the islets after retrieval from the transplanted area revealed significantly
      reduced apoptosis in ICCs. Transplantation of ICCs may be an attractive strategy
      to prevent islet cell apoptosis that results from nonimmune-mediated physiologic
      stress at the transplantation site.-Pathak, S., Regmi, S., Gupta, B., Pham, T.
      T., Yong, C. S., Kim, J. O., Yook, S., Kim, J.-R., Park, M. H., Bae, Y. K.,
      Jeong, J.-H. Engineered islet cell clusters transplanted into subcutaneous space
      are superior to pancreatic islets in diabetes.

PMID- 28754713
TI  - UBAP2L is amplified in a large subset of human lung adenocarcinoma and is
      critical for epithelial lung cell identity and tumor metastasis.
AB  - The ubiquitin-associated protein 2-like (UBAP2L) gene remains poorly studied in
      human and mouse development. UBAP2L interacts with the Polycomb group protein B
      lymphoma Mo-MLV insertion region 1 homolog (BMI1) and determines the activity of
      mouse hematopoietic stem cells in vivo Here we show that loss of Ubap2l leads to
      disorganized respiratory epithelium of mutant neonates, which die of respiratory
      failure. We also show that UBAP2L overexpression leads to epithelial-mesenchymal
      transition-like phenotype in a non-small cell lung carcinoma (NSCLC) cell line.
      UBAP2L is amplified in 15% of human primary lung adenocarcinoma specimens. Such
      patients express higher levels of UBAP2L and show a reduction in survival when
      compared with those who do not have this gene amplification. Supporting a
      possible role for UBAP2L in lung tumor progression, NSCLC cells engineered to
      express low levels of this gene produce much smaller tumors in vivo than wild
      type control cells. Together, these results suggest that UBAP2L contributes to
      epithelial lung cell identity in mice and that it plays an important role in
      human lung adenocarcinoma.-Aucagne, R., Girard, S., Mayotte, N., Lehnertz, B.,
      Lopes-Paciencia, S., Gendron, P., Boucher, G., Chagraoui, J., Sauvageau, G.
      UBAP2L is amplified in a large subset of human lung adenocarcinoma and is
      critical for epithelial lung cell identity and tumor metastasis.

PMID- 28754715
TI  - Changes of loggerhead turtle (Caretta caretta) dive behavior associated with
      tropical storm passage during the inter-nesting period.
AB  - To improve conservation strategies for threatened sea turtles, more knowledge on
      their ecology, behavior, and how they cope with severe and changing weather
      conditions is needed. Satellite and animal motion datalogging tags were used to
      study the inter-nesting behavior of two female loggerhead turtles in the Gulf of
      Mexico, which regularly has hurricanes and tropical storms during nesting season.
      We contrast the behavioral patterns and swimming energetics of these two turtles,
      the first tracked in calm weather and the second tracked before, during and after
      a tropical storm. Turtle 1 was highly active and swam at the surface or submerged
      95% of the time during the entire inter-nesting period, with a high estimated
      specific oxygen consumption rate (0.95 ml min-1 kg-0.83). Turtle 2 was inactive
      for most of the first 9 days of the inter-nesting period, during which she rested
      at the bottom (80% of the time) with low estimated oxygen consumption (0.62 ml
      min-1 kg-0.83). Midway through the inter-nesting period, turtle 2 encountered a
      tropical storm and became highly active (swimming 88% of the time during and 95%
      after the storm). Her oxygen consumption increased significantly to 0.97 ml min-1
      kg-0.83 during and 0.98 ml min-1 kg-0.83 after the storm. However, despite the
      tropical storm, turtle 2 returned to the nesting beach, where she successfully re
      nested 75 m from her previous nest. Thus, the tropical storm had a minor effect
      on this female's individual nesting success, even though the storm caused 90%
      loss nests at Casey Key.

PMID- 28754714
TI  - NRF1 coordinates with DNA methylation to regulate spermatogenesis.
AB  - Spermatogenesis is a highly coordinated process that requires tightly regulated
      gene expression programmed by transcription factors and epigenetic modifiers. In
      this study, we found that nuclear respiratory factor (NRF)-1, a key transcription
      factor for mitochondrial biogenesis, cooperated with DNA methylation to directly
      regulate the expression of multiple germ cell-specific genes, including Asz1 In
      addition, conditional ablation of NRF1 in gonocytes dramatically down-regulated
      these germline genes, blocked germ cell proliferation, and subsequently led to
      male infertility in mice. Our data highlight a precise crosstalk between
      transcriptional regulation by NRF1 and epigenetic modulation during germ cell
      development and unequivocally demonstrate a novel role of NRF1 in
      spermatogenesis.-Wang, J., Tang, C., Wang, Q., Su, J., Ni, T., Yang, W., Wang,
      Y., Chen, W., Liu, X., Wang, S., Zhang, J., Song, H., Zhu, J., Wang, Y. NRF1
      coordinates with DNA methylation to regulate spermatogenesis.

PMID- 28754716
TI  - Maximum thermal limits of coral reef damselfishes are size dependent and
      resilient to near-future ocean acidification.
AB  - Theoretical models predict that ocean acidification, caused by increased
      dissolved CO2, will reduce the maximum thermal limits of fishes, thereby
      increasing their vulnerability to rising ocean temperatures and transient
      heatwaves. Here, we tested this prediction in three species of damselfishes on
      the Great Barrier Reef, Australia. Maximum thermal limits were quantified using
      critical thermal maxima (CTmax) tests following acclimation to either present-day
      or end-of-century levels of CO2 for coral reef environments (~500 or ~1000 uatm,
      respectively). While species differed significantly in their thermal limits,
      whereby Dischistodus perspicillatus exhibited greater CTmax (37.88+/-0.03 degrees
      C; N=47) than Dascyllus aruanus (37.68+/-0.02 degrees C; N=85) and Acanthochromis
      polyacanthus (36.58+/-0.02 degrees C; N=63), end-of-century CO2 had no effect (D.
      aruanus) or a slightly positive effect (increase in CTmax of 0.16 degrees C in D.
      perspicillatus and 0.21 degrees C in A. polyacanthus) on CTmax Contrary to
      expectations, early-stage juveniles were equally as resilient to CO2 as larger
      conspecifics, and CTmax was higher at smaller body sizes in two species. These
      findings suggest that ocean acidification will not impair the maximum thermal
      limits of reef fishes, and they highlight the critical role of experimental
      biology in testing predictions of theoretical models forecasting the consequences
      of environmental change.

PMID- 28754717
TI  - Role of outstretched forelegs of flying beetles revealed and demonstrated by
      remote leg stimulation in free flight.
AB  - In flight, many insects fold their forelegs tightly close to the body, which
      naturally decreases drag or air resistance. However, flying beetles stretch out
      their forelegs for some reason. Why do they adopt this posture in flight? Here,
      we show the role of the stretched forelegs in flight of the beetle Mecynorrhina
      torquata Using leg motion tracking and electromyography in flight, we found that
      the forelegs were voluntarily swung clockwise in yaw to induce counter-clockwise
      rotation of the body for turning left, and vice versa. Furthermore, we
      demonstrated remote control of left-right turnings in flight by swinging the
      forelegs via a remote electrical stimulator for the leg muscles. The results and
      demonstration reveal that the beetle's forelegs play a supplemental role in
      directional steering during flight.

PMID- 28754718
TI  - Intracoronary delivery of recombinant TIMP-3 after myocardial infarction: effects
      on myocardial remodeling and function.
AB  - Ischemia-reperfusion (IR) and myocardial infarction (MI) cause adverse left
      ventricular (LV) remodeling and heart failure and are facilitated by an imbalance
      in matrix metalloproteinase (MMP) activation and the endogenous tissue inhibitors
      of metalloproteinase (TIMPs). We have identified that myocardial injections of
      recombinant TIMP-3 (rTIMP-3; human full length) can interrupt post-MI remodeling.
      However, whether and to what degree intracoronary delivery of rTIMP-3 post-IR is
      feasible and effective remained to be established. Pigs (25 kg) underwent
      coronary catheterization and balloon occlusion of the left anterior descending
      coronary artery (LAD) for 90 min whereby at the final 4 min, rTIMP-3 (30 mg, n =
      9) or saline was infused in the distal LAD. LV echocardiography was performed at
      3-28 days post-IR, and LV ejection fraction (EF) and LV end-diastolic volume were
      measured. LV EF fell and LV end-diastolic volume increased from baseline (pre-IR)
      values (66 +/- 1% and 40 +/- 1 ml, respectively, means +/- standard deviation) in
      both groups; however, the extent of LV dilation was reduced in the rTIMP-3 group
      by 40% at 28 days post-IR (P < 0.05) and the fall in LV EF was attenuated.
      Despite equivalent plasma troponin levels (14 +/- 3 ng/ml), computed MI size at
      28 days was reduced by over 45% in the rTIMP-3 group (P < 0.05), indicating that
      rTIMP-3 treatment abrogated MI expansion post-IR. Plasma NH2-terminal pro-brain
      natriuretic peptide levels, an index of heart failure progression, were reduced
      by 25% in the rTIMP-3 group compared with MI saline values (P < 0.05). Although
      the imbalance between MMPs and TIMPs has been recognized as a contributory factor
      for post-MI remodeling, therapeutic strategies targeting this imbalance have not
      been forthcoming. This study is the first to demonstrate that a relevant delivery
      approach (intracoronary) using rTIMP can alter the course of post-MI
      remodeling.NEW & NOTEWORTHY Myocardial ischemia and reperfusion injury remain
      significant causes of morbidity and mortality whereby alterations in the balance
      between matrix metalloproteinase and tissue inhibitor of metalloproteinase have
      been identified as contributory biological mechanisms. This novel translational
      study advances the concept of targeted delivery of recombinant proteins to modify
      adverse myocardial remodeling in ischemia-reperfusion injury.

PMID- 28754719
TI  - Visualization of three pathways for macromolecule transport across cultured
      endothelium and their modification by flow.
AB  - Transport of macromolecules across vascular endothelium and its modification by
      fluid mechanical forces are important for normal tissue function and in the
      development of atherosclerosis. However, the routes by which macromolecules cross
      endothelium, the hemodynamic stresses that maintain endothelial physiology or
      trigger disease, and the dependence of transendothelial transport on hemodynamic
      stresses are controversial. We visualized pathways for macromolecule transport
      and determined the effect on these pathways of different types of flow.
      Endothelial monolayers were cultured under static conditions or on an orbital
      shaker producing different flow profiles in different parts of the wells.
      Fluorescent tracers that bound to the substrate after crossing the endothelium
      were used to identify transport pathways. Maps of tracer distribution were
      compared with numerical simulations of flow to determine effects of different
      shear stress metrics on permeability. Albumin-sized tracers dominantly crossed
      the cultured endothelium via junctions between neighboring cells, high-density
      lipoprotein-sized tracers crossed at tricellular junctions, and low-density
      lipoprotein-sized tracers crossed through cells. Cells aligned close to the angle
      that minimized shear stresses across their long axis. The rate of paracellular
      transport under flow correlated with the magnitude of these minimized transverse
      stresses, whereas transport across cells was uniformly reduced by all types of
      flow. These results contradict the long-standing two-pore theory of solute
      transport across microvessel walls and the consensus view that endothelial cells
      align with the mean shear vector. They suggest that endothelial cells minimize
      transverse shear, supporting its postulated proatherogenic role. Preliminary data
      show that similar tracer techniques are practicable in vivo.NEW & NOTEWORTHY
      Solutes of increasing size crossed cultured endothelium through intercellular
      junctions, through tricellular junctions, or transcellularly. Cells aligned to
      minimize the shear stress acting across their long axis. Paracellular transport
      correlated with the level of this minimized shear, but transcellular transport
      was reduced uniformly by flow regardless of the shear profile.

PMID- 28754720
TI  - TERT Promoter Hypermethylation in Gastrointestinal Cancer: A Potential Stool
      Biomarker.
AB  - BACKGROUND: There is a high demand for noninvasive screening tools for
      gastrointestinal cancer (GIC) detection, and GIC-specific markers are required
      for such purposes. It is established that induction of the telomerase reverse
      transcriptase gene (TERT) coupled with telomerase activation is essential for
      cancer development/progression and aberrant TERT promoter methylation of specific
      5'-C-phosphate-G-3' (CpGs) has been linked to TERT induction in oncogenesis. Here
      we analyzed TERT promoter methylation in fecal samples from GIC patients and
      healthy adults and determined its value as a stool biomarker for GIC detection.
      MATERIALS AND METHODS: Sixty-nine GIC patients (34 colorectal carcinoma and 35
      gastric cancer) and 62 healthy adults were recruited and fecal samples were
      collected. Paired tumors and adjacent non-cancerous tissues from 34 patients and
      normal mucosa tissues from 12 healthy individuals were collected. TERT promoter
      methylation density was determined using pyrosequencing. RESULTS: We identified
      two GIC-specific methylation sites at -218 (CpG site 1) and -210 (CpG site 2) in
      the TERT promoter in tumor tissues. Methylated TERT promoter CpG sites 1 and 2
      were also detectable in patient stool, while only background levels were observed
      in healthy individuals. The overall sensitivity reached 52.2% (95% confidence
      interval [CI]: 48.3-56.0) for fecal methylated TERT promoter assays at 90%
      specificity, which was comparable to other known stool methylation markers for
      GIC detection. The combined assays of fecal TERT promoter methylation and occult
      blood (OB) significantly improved sensitivity and specificity in colorectal
      cancer (area under curves for methylation alone: 0.798, 95% CI: 0.707-0.889 vs.
      methylation + OB: 0.920, 95% CI: 0.859-0.981; p = .028), but not in gastric
      cancer. CONCLUSION: This proof-of-concept study suggests the feasibility of stool
      TERT promoter methylation analyses as an additional tool in noninvasive GIC
      screening. IMPLICATIONS FOR PRACTICE: Induction of telomerase reverse
      transcriptase (TERT) expression coupled with telomerase activation is essential
      for cancer development/progression, while aberrant TERT promoter methylation has
      been linked to TERT induction in oncogenesis. We identified two cancer-specific
      methylation sites (CpG1 and 2) in the TERT promoter in tumors from GIC patients.
      Methylated TERT promoter CpG sites 1 and 2 were detectable in patient stool,
      while only background levels were observed in healthy individuals. The
      sensitivity and specificity was comparable to other known stool methylation
      markers for GIC detection. This proof-of-concept study suggests the feasibility
      of stool TERT promoter methylation analyses for noninvasive screening of GIC.

PMID- 28754721
TI  - Activity of Pazopanib and Trabectedin in Advanced Alveolar Soft Part Sarcoma.
AB  - BACKGROUND: Alveolar soft part sarcoma (ASPS) is an exceedingly rare and orphan
      disease, without active drugs approved in the front line. Pazopanib and
      trabectedin are licensed for sarcoma treatment from second-line, but very little
      and contradictory data are available on their activity in ASPS. Lacking ongoing
      and/or planned clinical trials, we conducted a multi-institutional study
      involving the reference sites for sarcoma in Europe, U.S., and Japan, within the
      World Sarcoma Network, to investigate the efficacy of pazopanib and trabectedin.
      MATERIALS AND METHODS: From May 2007, 14 of the 27 centers that were asked to
      retrospectively review their databases had identified 44 advanced ASPS patients
      treated with pazopanib and/or trabectedin. Response was evaluated by Response
      Evaluation Criteria in Solid Tumors 1.1. Progression-free survival (PFS) and
      overall survival (OS) were computed by Kaplan-Meier method. RESULTS: Among 30
      patients who received pazopanib, 18 were pretreated (13 with other
      antiangiogenics). Response was evaluable in 29/30 patients. Best responses were 1
      complete response, 7 partial response (PR), 17 stable disease (SD), and 4
      progressions. At a 19-month median follow-up, median PFS was 13.6 months (range:
      1.6-32.2+), with 59% of patients progression-free at 1 year. Median OS was not
      reached.Among 23 patients treated with trabectedin, all were pretreated and
      evaluable for response. Best responses were 1 PR, 13 SD, and 9 progressions. At a
      27-month median follow-up, median PFS was 3.7 months (range: 0.7-109), with 13%
      of patients progression-free at 1 year. Median OS was 9.1 months. CONCLUSION: The
      value of pazopanib in advanced ASPS is confirmed, with durable responses, whereas
      the value of trabectedin appears limited. These results are relevant to defining
      the best approach to advanced ASPS. IMPLICATIONS FOR PRACTICE: This retrospective
      study, conducted among the world reference centers for treatment of sarcoma,
      confirms the value of pazopanib in patients with advanced alveolar soft part
      sarcoma (ASPS), with dimensional and durable responses, whereas trabectedin shows
      a limited activity. Alveolar soft part sarcoma is resistant to conventional
      cytotoxic chemotherapy. Pazopanib and trabectedin are licensed for treatment of
      sarcoma from second line; in the lack of prospective clinical trials, these
      results are relevant to defining ASPS best management and strongly support
      initiatives aimed at obtaining the approval of pazopanib in the front line of the
      disease.

PMID- 28754722
TI  - Fixed Dosing of Monoclonal Antibodies in Oncology.
AB  - : Most monoclonal antibodies in oncology are administered in body-size-based
      dosing schedules. This is believed to correct for variability in both drug
      distribution and elimination between patients. However, monoclonal antibodies
      typically distribute to the blood plasma and extracellular fluids only, which
      increase less than proportionally with the increase in body weight. Elimination
      takes place via proteolytic catabolism, a nonspecific immunoglobulin G
      elimination pathway, and intracellular degradation after binding to the target.
      The latter is the primary route of elimination and is related to target
      expression levels rather than body size. Taken together, the minor effects of
      body size on distribution and elimination of monoclonal antibodies and their
      usually wide therapeutic window do not support body-size-based dosing. We
      evaluated effects of body weight on volume of distribution and clearance of
      monoclonal antibodies in oncology and show that a fixed dose for most of these
      drugs is justified based on pharmacokinetics. A survey of the savings after fixed
      dosing of monoclonal antibodies at our hospital showed that fixed dosing can
      reduce costs of health care, especially when pooling of preparations is not
      possible (which is often the case in smaller hospitals). In conclusion, based on
      pharmacokinetic parameters of monoclonal antibodies, there is a rationale for
      fixed dosing of these drugs in oncology. Therefore, we believe that fixed dosing
      is justified and can improve efficiency of the compounding. Moreover, drug
      spillage can be reduced and medication errors may become less likely.
      IMPLICATIONS FOR PRACTICE: The currently available knowledge of elimination of
      monoclonal antibodies combined with the publicly available data from clinical
      trials and extensive population pharmacokinetic (PopPK) modeling justifies fixed
      dosing. Interpatient variation in exposure is comparable after body weight and
      fixed dosing and most monoclonal antibodies show relatively flat dose-response
      relationships. For monoclonal antibodies, this results in wide therapeutic
      windows and no reduced clinical efficacy after fixed dosing. Therefore, we
      believe that fixed dosing at a well-selected dose can increase medication safety
      and help in reduction of costs of health care without the loss of efficacy or
      safety margins.

PMID- 28754723
TI  - A Functional Link Between Bir1 and the Saccharomyces cerevisiae Ctf19 Kinetochore
      Complex Revealed Through Quantitative Fitness Analysis.
AB  - The chromosomal passenger complex (CPC) is a key regulator of eukaryotic cell
      division, consisting of the protein kinase Aurora B/Ipl1 in association with its
      activator (INCENP/Sli15) and two additional proteins (Survivin/Bir1 and
      Borealin/Nbl1). Here, we report a genome-wide genetic interaction screen in
      Saccharomyces cerevisiae using the bir1-17 mutant, identifying through
      quantitative fitness analysis deletion mutations that act as enhancers and
      suppressors. Gene knockouts affecting the Ctf19 kinetochore complex were
      identified as the strongest enhancers of bir1-17, while mutations affecting the
      large ribosomal subunit or the mRNA nonsense-mediated decay pathway caused strong
      phenotypic suppression. Thus, cells lacking a functional Ctf19 complex become
      highly dependent on Bir1 function and vice versa. The negative genetic
      interaction profiles of bir1-17 and the cohesin mutant mcd1-1 showed considerable
      overlap, underlining the strong functional connection between sister chromatid
      cohesion and chromosome biorientation. Loss of some Ctf19 components, such as
      Iml3 or Chl4, impacted differentially on bir1-17 compared with mutations
      affecting other CPC components: despite the synthetic lethality shown by either
      iml3? or chl4? in combination with bir1-17, neither gene knockout showed any
      genetic interaction with either ipl1-321 or sli15-3 Our data therefore imply a
      specific functional connection between the Ctf19 complex and Bir1 that is not
      shared with Ipl1.

PMID- 28754724
TI  - Trans-ancestry Fine Mapping and Molecular Assays Identify Regulatory Variants at
      the ANGPTL8 HDL-C GWAS Locus.
AB  - Recent genome-wide association studies (GWAS) have identified variants associated
      with high-density lipoprotein cholesterol (HDL-C) located in or near the ANGPTL8
      gene. Given the extensive sharing of GWAS loci across populations, we
      hypothesized that at least one shared variant at this locus affects HDL-C. The
      HDL-C-associated variants are coincident with expression quantitative trait loci
      for ANGPTL8 and DOCK6 in subcutaneous adipose tissue; however, only ANGPTL8
      expression levels are associated with HDL-C levels. We identified a 400-bp
      promoter region of ANGPTL8 and enhancer regions within 5 kb that contribute to
      regulating expression in liver and adipose. To identify variants functionally
      responsible for the HDL-C association, we performed fine-mapping analyses and
      selected 13 candidate variants that overlap putative regulatory regions to test
      for allelic differences in regulatory function. Of these variants, rs12463177-G
      increased transcriptional activity (1.5-fold, P = 0.004) and showed differential
      protein binding. Six additional variants (rs17699089, rs200788077, rs56322906,
      rs3760782, rs737337, and rs3745683) showed evidence of allelic differences in
      transcriptional activity and/or protein binding. Taken together, these data
      suggest a regulatory mechanism at the ANGPTL8 HDL-C GWAS locus involving tissue
      selective expression and at least one functional variant.

PMID- 28754727
TI  - Defra presses on with TB target.

PMID- 28754728
TI  - Shortage occupation list: an 'essential step' to tackle workforce issues.

PMID- 28754725
TI  - Genome-Wide Analysis of the First Sequenced Mycoplasma capricolum subsp.
      capripneumoniae Strain M1601.
AB  - Mycoplasma capricolum subsp. capripneumoniae (Mccp) is a common pathogen of goats
      that causes contagious caprine pleuropneumonia. We closed the gap and corrected
      rRNA operons in the draft genome of Mccp M1601: a strain isolated from an
      infected goat in a farm in Gansu, China. The genome size of M1601 is 1,016,707 bp
      with a GC content of 23.67%. We identified 915 genes (occupying 90.27% of the
      genome), of which 713 are protein-coding genes (excluding 163 pseudogenes). No
      genomic islands and complete insertion sequences were found in the genome.
      Putative determinants associated with the organism's virulence were analyzed, and
      26 genes (including one adhesion protein gene, two capsule synthesis gene
      clusters, two lipoproteins, hemolysin A, ClpB, and proteins involved in pyruvate
      metabolism and cation transport) were potential virulence factors. In addition,
      two transporter systems (ATP-binding cassette [ABC] transporters and
      phosphotransferase) and two secretion systems (Sec and signal recognition
      particle [SRP] pathways) were observed in the Mccp genome. Genome synteny
      analysis reveals a good collinear relationship between M1601 and Mccp type strain
      F38. Phylogenetic analysis based on 11 single-copy core genes of 31 Mycoplasma
      strains revealed good collinearity between M1601 and Mycoplasma capricolum subsp.
      capricolum (Mcc) and close relationship among Mycoplasma mycoides cluster
      strains. Our genome-wide analysis of Mccp M1601 provides helpful information on
      the pathogenic mechanisms and genetics of Mccp.

PMID- 28754730
TI  - Sector-specific targets for antibiotic use with VMD.

PMID- 28754731
TI  - Will Brexit lead to 'race to the bottom' for UK food animal welfare standards?

PMID- 28754733
TI  - Public urged to surrender ivory in UK-wide scheme.

PMID- 28754734
TI  - Equine disease surveillance: quarterly summary.
AB  - This quarterly equine disease surveillance report, prepared by Defra, the Animal
      Health Trust and the British Equine Veterinary Association, covers: Summary of
      surveillance testing, January to March 2017International disease occurrence in
      the first quarter of 2017Focus on the diagnosis of equine influenza.

PMID- 28754735
TI  - Diagnosis of equine influenza.
AB  - During the summer months, there will be increased movement and, therefore,
      increased mixing of the horse population, leading to a higher risk of disease
      transmission and subsequent clinical cases. It is important that both vets and
      owners remain vigilant for equine influenza infection. Here, Adam Rash, of the
      Animal Health Trust, discusses the diagnosis of this disease.

PMID- 28754736
TI  - Preparing for the worst: African swine fever in China.

PMID- 28754737
TI  - Pig empire under infectious threat: risk of African swine fever introduction into
      the People's Republic of China.
AB  - Pig production and pork consumption are very important to the People's Republic
      of China for both economic and cultural reasons. The incursion and spread of a
      disease such as African swine fever (ASF), which emerged in Eastern Europe in
      2007, could have devastating socioeconomic consequences for both the Chinese and
      the global pig industry. The Chinese government consequently attributes a very
      high priority to ASF and is actively seeking to improve its preparedness. This
      paper discusses different drivers and pathways of potential emergence of ASF in
      China in light of the country's specificities, including international movements
      of people, pigs and pig products, swill feeding practices and wild boar
      populations. It suggests that effective ASF risk management in China will require
      a comprehensive and integrated approach linking science and policy and will need
      to involve all relevant stakeholders to develop realistic policies.

PMID- 28754738
TI  - Why are we embarrassed by our costs?

PMID- 28754739
TI  - Rumen fluke in South American camelids in Great Britain.

PMID- 28754740
TI  - Antibiotic use in the poultry industry.

PMID- 28754742
TI  - Learning to teach.
AB  - In the third year of her PhD at Cambridge, Myfanwy Hill dipped into her skills
      toolbox to see what competences she has and what she still needs. So, with one
      eye on the newly fashionable 'portfolio career', and one eye on the unachieved
      goals on her bucket list, she signed up to teach undergraduate veterinary and
      medical students.

PMID- 28754741
TI  - Hunting with hounds.

PMID- 28754743
TI  - Ten-minute chat.
AB  - Aimee Paterson-Young from White Cross Vets understands that learning to place an
      intravenous catheter on a live animal can be stressful for student veterinary
      nurses, so she makes fake legs for them to practise on.

PMID- 28754746
TI  - Tumor-derived exosomes modulate PD-L1 expression in monocytes.
AB  - In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed
      toward protumorigenic phenotypes, including the release of tumor-supportive
      cytokines and the expression of immunosuppressive molecules such as programmed
      cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic
      skewing in CLL, we evaluated the role of tumor cell-derived exosomes in the cross
      talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL
      derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA
      species that is enriched in exosomes from plasma of CLL patients compared with
      healthy donor samples. Transfer of CLL-derived exosomes or hY4 alone to monocytes
      resulted in key CLL-associated phenotypes, including the release of cytokines,
      such as C-C motif chemokine ligand 2 (CCL2), CCL4, and interleukin-6, and the
      expression of PD-L1. These responses were abolished in Toll-like receptor 7
      (TLR7)-deficient monocytes, suggesting exosomal hY4 as a driver of TLR7
      signaling. Pharmacologic inhibition of endosomal TLR signaling resulted in a
      substantially reduced activation of monocytes in vitro and attenuated CLL
      development in vivo. Our results indicate that exosome-mediated transfer of
      noncoding RNAs to monocytes contributes to cancer-related inflammation and
      concurrent immune escape via PD-L1 expression.

PMID- 28754744
TI  - KLB, encoding beta-Klotho, is mutated in patients with congenital
      hypogonadotropic hypogonadism.
AB  - Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic form of isolated
      gonadotropin-releasing hormone (GnRH) deficiency caused by mutations in > 30
      genes. Fibroblast growth factor receptor 1 (FGFR1) is the most frequently mutated
      gene in CHH and is implicated in GnRH neuron development and maintenance. We note
      that a CHH FGFR1 mutation (p.L342S) decreases signaling of the metabolic
      regulator FGF21 by impairing the association of FGFR1 with beta-Klotho (KLB), the
      obligate co-receptor for FGF21. We thus hypothesized that the metabolic
      FGF21/KLB/FGFR1 pathway is involved in CHH Genetic screening of 334 CHH patients
      identified seven heterozygous loss-of-function KLB mutations in 13 patients (4%).
      Most patients with KLB mutations (9/13) exhibited metabolic defects. In mice,
      lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility
      due to a hypothalamic defect associated with inability of GnRH neurons to release
      GnRH in response to FGF21. Peripheral FGF21 administration could indeed reach
      GnRH neurons through circumventricular organs in the hypothalamus. We conclude
      that FGF21/KLB/FGFR1 signaling plays an essential role in GnRH biology,
      potentially linking metabolism with reproduction.

PMID- 28754747
TI  - Disseminated tuberculosis in relatively asymptomatic young woman.

PMID- 28754748
TI  - A perforated caecal volvulus in the foramen of Winslow.
AB  - The aim of this report is to discuss with high-quality images, a case of a caecal
      volvulus herniating through the foramen of Winslow with signs of perforation.

PMID- 28754749
TI  - Hypertrophic olivary degeneration.

PMID- 28754750
TI  - Postoperative gluteal compartment syndrome following microsurgical free-flap hand
      reconstruction: the importance of early recognition and treatment.
AB  - Compartment syndrome, a surgical emergency, is caused by an increase in pressure
      within a closed osseofascial space, often due to trauma. This causes a decrease
      in tissue perfusion and ultimately tissue necrosis and multiorgan failure if not
      treated in a timely fashion. Gluteal compartment syndrome is a rare variant and
      often caused by a period of immobilisation secondary to intoxication with alcohol
      or drugs or during long operations, typically in the supine position. We report
      on a case of gluteal compartment syndrome developing in a patient postoperatively
      following a long microsurgical procedure to a hand, which has not been documented
      before. Although rare, we highlight the clinical course and diagnostic criteria,
      which are essential for early identification and treatment.

PMID- 28754751
TI  - Intraparotid ductal ectasia: rare cause of parotid swelling.
AB  - A 41-year-old patient was hospitalised for a chronic right parotid mass. A
      cervical ultrasound revealed a cystic mass of the parotid. Cervical MRI found a
      ductal ectasia of the parotid and submandibular glands associated with a
      retention cyst of the right parotid. He had a right total parotidectomy.
      Histopathological examination of the lesion revealed a multilocular cystic mass
      with a diffuse glandular ectasia of salivary ducts. The patient had an uneventful
      postoperative course without any recurrence of symptoms.

PMID- 28754752
TI  - Reversible Holmes' tremor due to spontaneous intracranial hypotension.
AB  - Holmes' tremor is a low-frequency hand tremor and has varying amplitude at
      different phases of motion. It is usually unilateral and does not respond
      satisfactorily to drugs and thus considered irreversible. Structural lesions in
      the thalamus and brainstem or cerebellum are usually responsible for Holmes'
      tremor. We present a 23-year-old woman who presented with unilateral Holmes'
      tremor. She also had hypersomnolence and headache in the sitting posture. Her
      brain imaging showed brain sagging and deep brain swelling due to spontaneous
      intracranial hypotension (SIH). She was managed conservatively and had a total
      clinical and radiological recovery. The brain sagging with the consequent
      distortion of the midbrain and diencephalon was responsible for this clinical
      presentation. SIH may be considered as one of the reversible causes of Holmes'
      tremor.

PMID- 28754753
TI  - Hiatal hernia mimicking heart problems.

PMID- 28754754
TI  - Gamna-Gandy nodules of the spleen and asplenism in SLE: a novel association?

PMID- 28754755
TI  - Bacteraemia and liver abscess due to Fusobacterium necrophorum.
AB  - Fusobacterium necrophorum is the oropharyngeal pathogen usually associated with
      Lemierre's syndrome, a pharyngeal infection which evolves to sepsis, septic
      emboli and thrombophlebitis of the adjacent neck vessels. It is an uncommon
      causative bacteria of a liver abscess, and an extensive workup should, therefore,
      be performed in order to rule out potential sources of the infection. This case
      report describes the workup that led to the diagnosis of a colorectal carcinoma,
      which was deemed to be the source of the Fusobacterium bacteraemia.

PMID- 28754756
TI  - Androgenic alopecia: an entity to consider in adolescence.

PMID- 28754757
TI  - Adjunctive extracorporeal carbon dioxide removal in refractory status
      asthmaticus.
AB  - Status asthmaticus (SA) is a life-threatening disorder. Severe respiratory
      failure may require extracorporeal membrane oxygenation (ECMO). Previous reports
      have demonstrated utility of ECMO in SA in various patients with varying success.
      A 25-year-old man was admitted with status asthmatics and severe hypercapnic
      respiratory failure. Despite tailored ventilator therapies, such as pressure
      control ventilation and maximal pharmacological therapy, including general
      anaesthesia, the patienta?TMs condition deteriorated rapidly. Veno-venous ECMO
      (VV-ECMO) was provided for respiratory support. The patienta?TMs clinical
      condition improved over the following 72a?0/00hours and was discharged from the
      intensive care unit on day 3. This case report demonstrates the successful use of
      VV-ECMO in a patient with severe respiratory failure due to SA, who failed to
      respond to maximal therapy. This case adds support to a growing body of
      literature that shows that ECMO can be used with success for refractory status
      asthmaticus.

PMID- 28754758
TI  - Acquired pachydermatoglyphia: the cutaneous manifestation of pulmonary tumours.

PMID- 28754759
TI  - Extramacular dome-shaped elevation: a novel finding in a case of high myopia.

PMID- 28754760
TI  - Accidental hypothermic cardiac arrest and rapid mediastinal warming with pleural
      lavage: a survivor after 3.5 hours of manual CPR.
AB  - A 30-year-old man suffered post-traumatic hypothermic cardiac arrest. On arrival
      in the emergency department, rectal core temperature was 23 degrees C. Manual
      cardiopulmonary resuscitation (CPR) was continued as no mechanical chest
      compression device was available, and active and passive rewarming was
      undertaken. Bilateral thoracostomies confirmed good lung inflation.
      Defibrillation and intravenous epinephrine were discontinued until core
      temperature was elevated above 30 degrees C. Extracorporeal rewarming was
      unavailable. When no increase in rectal temperature was achieved after 90 min, an
      alternative oesophageal probe confirmed mediastinal temperature as 23 degrees C.
      Bilateral chest drain insertion, followed by microwave-heated saline pleural
      lavage, rapidly raised the oesophageal temperature above 30 degrees C with
      subsequent successful defibrillation, initially to pulseless electrical activity
      and finally return of spontaneous circulation 3.5 hours after the commencement of
      CPR. The patient recovered fully and was discharged without neurological deficit.
      Rapid mediastinal warming with pleural lavage should be considered in units with
      no access to extracorporeal rewarming service.

PMID- 28754761
TI  - Directly observed therapy for clozapine with concomitant methadone prescription:
      a method for improving adherence and outcome.
AB  - A young male presented with many years of delusions and hallucinations, with
      concurrent heroin use and subsequent amphetamine uses. There were no depressive
      or manic symptoms and psychotic symptoms prior to the amphetamine use. After the
      trials of two atypical antipsychotics and later clozapine due to treatment
      resistance, adherence and functionality were poor and there was still persistent
      drug use. As a result, a long acting injectable adjunct was commenced, but only
      minimal effects were observed. However after initiation of directly observed
      treatment of clozapine with methadone, there has been functional and clinical
      response and drug use has ceased.

PMID- 28754762
TI  - Sclerosing lymphangitis of the penis associated with marked penile oedema and
      skin erosions.
AB  - Sclerosing lymphangitis of the penis is a benign, under-reported condition
      consisting of a asymptomatic firm cord-like swelling around the coronal sulcus of
      the penis usually affecting men in the second or third decade of life. Penile
      oedema and erosions are rarely reported. Clinical signs may be remarkable
      contrasting with the self-limited character of the disease. We report a new case
      of sclerosing lymphangitis of the penis occurring in a 59-year-old patient marked
      by penile swelling and several overlying skin erosions, and discuss the clinical
      features and the pathogenesis aspects of the disease.

PMID- 28754763
TI  - Henry Wellcome: the man who made medicine.

PMID- 28754764
TI  - Plastome sequences of an ancient fern lineage reveal remarkable changes in gene
      content and architecture.
AB  - PREMISE OF THE STUDY: Comparative analyses of plastid genomes have suggested that
      gene order and content are relatively stable across the main groups of land
      plants, with significant changes rarely reported. We examine plastome
      organization and RNA editing in ferns and report changes that add valuable
      information on plastome evolution in land plants. METHODS: Using next-generation
      sequencing methods, we fully sequenced plastomes from three species of
      Schizaeaceae, and compared their plastomes with other groups of land plants to
      study changes in gene composition, plastome architecture, and putative RNA
      editing sites. We also performed maximum likelihood and Bayesian inference
      phylogenetic analyses using 46 plastid-encoded genes, including 26 ferns, two
      gymnosperms, and five angiosperms. KEY RESULTS: Within Schizaeaceae, plastomes
      were similar to each other in gene content and architecture. Striking changes
      compared with other ferns include the complete loss of ndh genes and reduction of
      the small single copy. Putative RNA editing was identified in all three
      plastomes, a characteristic that is shared with other fern groups. The monophyly
      of Schizaeales and Schizaeaceae was confirmed. CONCLUSIONS: The plastomes of
      Schizaea are the smallest reported for a fern so far. The loss of the ndh gene
      suite is associated with the reduction of the small single copy, instead of the
      inverted repeat as noted for other groups of plants. Putative C-to-U and U-to-C
      transitions were observed in several instances in the three plastomes, suggesting
      that posttranscriptional modification of RNA is likely a common phenomenon in
      this clade as well.

PMID- 28754765
TI  - Intraspecific life history variation in contrasting habitats: Insights from an
      obligate symbiotic organism.
AB  - PREMISE OF THE STUDY: Life history theory predicts that plants in unfavorable
      habitats for juvenile growth and survival will commence reproduction at smaller
      sizes and exhibit higher reproductive allocations than those in favorable
      habitats. The scope of life history theory will increase if these predictions
      apply to a broad range of organisms. Populations of organisms in contrasting
      habitats may experience different demographic rates. Thus, we compared the
      demography and life history traits of a lichen species in contrasting habitats.
      METHODS: We compared the abundance, growth, mortality, and reproductive strategy
      (threshold size for reproduction and reproductive allometry) of epiphytic and
      saxicolous populations of the asexually reproducing lichen Lobarina scrobiculata
      in two oak forests in central Spain. KEY RESULTS: The growth rates of saxicolous
      individuals were two times faster than those of epiphytic individuals. Epiphytic
      specimens exhibited a smaller threshold size for reproduction and a higher
      reproductive allocation than their saxicolous counterparts. The populations
      hosted by trees were two times larger than those on rocks (13,788 vs. 6629
      individuals, respectively). The mortality rate did not vary between habitats.
      CONCLUSIONS: Our results demonstrate that contrasting habitats selected for
      differences in the demography and life history traits of a lichen species.
      Consistent with life history theory predictions, in the habitat with slower
      growth, L. scrobiculata started to reproduce at a smaller size and its
      reproductive allocation was higher. This study extends the scope of life history
      theory and improves our understanding of life history patterns and variations in
      overlooked taxa such as lichens.

PMID- 28754766
TI  - Divergent evolution and niche differentiation within the common peatmoss Sphagnum
      magellanicum.
AB  - PREMISE OF THE STUDY: Populations with phenotypic polymorphism in discrete
      characters may be good models for investigating genome evolution and speciation.
      Sphagnum magellanicum Brid. is found throughout the northern hemisphere, and
      despite considerable variation in morphological characters, it is considered one
      of the least taxonomically controversial peatmoss species. We have observed two
      main morphs of the species associated with different microhabitats. Here we
      investigated the genomic and environmental basis of this intraspecific
      morphological variation. METHODS: We conducted transplant and common garden
      experiments to test whether the two morphs are genetically differentiated. We
      then used RAD-sequencing to quantify the genomic divergence between the morphs
      and approximate Bayesian computation (ABC) to infer the most likely demographic
      scenario explaining the genome-wide differentiation of the two morphs. KEY
      RESULTS: We found that genomic differentiation between the two morphs is
      unexpectedly high and that several of the differentiated morphological characters
      have a genetic basis. Using simulation approaches, we found support for a
      scenario of ancient divergence followed by recent secondary contact. CONCLUSIONS:
      We show that the two morphs represent the two main genetic clusters previously
      found worldwide. Our results demonstrate that relatively minor morphological
      differentiation in a presumed phenotypically plastic peatmoss may be associated
      with massive divergence across the genome.

PMID- 28754767
TI  - Proteasomal inhibition restores biological function of mis-sense mutated
      dysferlin in patient-derived muscle cells.

PMID- 28754768
TI  - Modular dispensability of dysferlin C2 domains reveals rational design for mini
      dysferlin molecules.

PMID- 28754769
TI  - Correction for Zehorai and Seger, "Beta-Like Importins Mediate the Nuclear
      Translocation of Mitogen-Activated Protein Kinases".

PMID- 28754770
TI  - Correction for Lin et al., "Protein Tyrosine Phosphatase-Like A Regulates
      Myoblast Proliferation and Differentiation through MyoG and the Cell Cycling
      Signaling Pathway".

PMID- 28754771
TI  - Correction for Shah et al., "A Deacetylase-Deficient SIRT1 Variant Opposes Full
      Length SIRT1 in Regulating Tumor Suppressor p53 and Governs Expression of Cancer
      Related Genes".

PMID- 28754772
TI  - Correction for Fukunaga et al., "Activation of Protein Kinase Tel1 through
      Recognition of Protein-Bound DNA Ends".

PMID- 28754773
TI  - Correction for Copetti et al., "p65/RelA Modulates BECN1 Transcription and
      Autophagy".

PMID- 28754774
TI  - Correction for Travesa et al., "Repression of G1/S Transcription Is Mediated via
      Interaction of the GTB Motifs of Nrm1 and Whi5 with Swi6".

PMID- 28754775
TI  - Retraction for Sorek et al., "Activation Status-Coupled Transient S Acylation
      Determines Membrane Partitioning of a Plant Rho-Related GTPase".

PMID- 28754776
TI  - The HLF/IL-6/STAT3 feedforward circuit drives hepatic stellate cell activation to
      promote liver fibrosis.
AB  - BACKGROUND AND AIMS: Liver fibrosis is a wound-healing response that disrupts the
      liver architecture and function by replacing functional parenchyma with scar
      tissue. Recent progress has advanced our knowledge of this scarring process, but
      the detailed mechanism of liver fibrosis is far from clear. METHODS: The fibrotic
      specimens of patients and HLF (hepatic leukemia factor)PB/PB mice were used to
      assess the expression and role of HLF in liver fibrosis. Primary murine hepatic
      stellate cells (HSCs) and human HSC line Lx2 were used to investigate the impact
      of HLF on HSC activation and the underlying mechanism. RESULTS: Expression of HLF
      was detected in fibrotic livers of patients, but it was absent in the livers of
      healthy individuals. Intriguingly, HLF expression was confined to activated HSCs
      rather than other cell types in the liver. The loss of HLF impaired primary HSC
      activation and attenuated liver fibrosis in HLFPB/PB mice. Consistently, ectopic
      HLF expression significantly facilitated the activation of human HSCs.
      Mechanistic studies revealed that upregulated HLF transcriptionally enhanced
      interleukin 6 (IL-6) expression and intensified signal transducer and activator
      of transcription 3 (STAT3) phosphorylation, thus promoting HSC activation.
      Coincidentally, IL-6/STAT3 signalling in turn activated HLF expression in HSCs,
      thus completing a feedforward regulatory circuit in HSC activation. Moreover,
      correlation between HLF expression and alpha-smooth muscle actin, IL-6 and p
      STAT3 levels was observed in patient fibrotic livers, supporting the role of
      HLF/IL-6/STAT3 cascade in liver fibrosis. CONCLUSIONS: In aggregate, we delineate
      a paradigm of HLF/IL-6/STAT3 regulatory circuit in liver fibrosis and propose
      that HLF is a novel biomarker for activated HSCs and a potential target for
      antifibrotic therapy.

PMID- 28754777
TI  - Quantitative liver MRI including extracellular volume fraction for non-invasive
      quantification of liver fibrosis: a prospective proof-of-concept study.

PMID- 28754778
TI  - Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years
      of age: a report from the Prospective Lynch Syndrome Database.
AB  - BACKGROUND: Most patients with path_MMR gene variants (Lynch syndrome (LS)) now
      survive both their first and subsequent cancers, resulting in a growing number of
      older patients with LS for whom limited information exists with respect to cancer
      risk and survival. OBJECTIVE AND DESIGN: This observational, international,
      multicentre study aimed to determine prospectively observed incidences of cancers
      and survival in path_MMR carriers up to 75 years of age. RESULTS: 3119 patients
      were followed for a total of 24 475 years. Cumulative incidences at 75 years
      (risks) for colorectal cancer were 46%, 43% and 15% in path_MLH1, path_MSH2 and
      path_MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer
      10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or
      pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%;
      for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%,
      respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper
      gastrointestinal, urinary tract and prostate cancers occurred predominantly at
      older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder
      93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas
      0%. Path_PMS2 carriers had lower risk for cancer. CONCLUSION: Carriers of
      different path_MMR variants exhibit distinct patterns of cancer risk and survival
      as they age. Risk estimates for counselling and planning of surveillance and
      treatment should be tailored to each patient's age, gender and path_MMR variant.
      We have updated our open-access website www.lscarisk.org to facilitate this.

PMID- 28754780
TI  - 2017 National Standards for Diabetes Self-Management Education and Support.

PMID- 28754779
TI  - Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to
      modify risk for alcoholic and non-alcoholic chronic pancreatitis.
AB  - OBJECTIVE: Alcohol-related pancreatitis is associated with a disproportionately
      large number of hospitalisations among GI disorders. Despite its clinical
      importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is
      poorly characterised. To identify risk genes for alcoholic CP and to evaluate
      their relevance in non-alcoholic CP, we performed a genome-wide association study
      and functional characterisation of a new pancreatitis locus. DESIGN: 1959
      European alcoholic CP patients and population-based controls from the KORA, LIFE
      and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA
      consortium (n=1332) were screened with Illumina technology. For replication,
      three European cohorts comprising 1650 patients with non-alcoholic CP and 6695
      controls originating from the same countries were used. RESULTS: We replicated
      previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in
      alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a
      new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35,
      95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus
      was in linkage disequilibrium with the CP-associated SNPs and was best tagged by
      rs8048956. The association was replicated in three independent European non
      alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to
      1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms
      and thereby affects protective trypsinogen degradation and ultimately
      pancreatitis risk. CONCLUSION: An inversion in the CTRB1-CTRB2 locus modifies
      risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms
      are involved in these inflammatory disorders.

PMID- 28754781
TI  - Nongenomic modulation of the large conductance voltage- and Ca2+-activated K+
      channels by estrogen: A novel regulatory mechanism in human detrusor smooth
      muscle.
AB  - Estrogens have an important role in regulating detrusor smooth muscle (DSM)
      function. However, the underlying molecular and cellular mechanisms by which
      estrogens control human DSM excitability and contractility are not well known.
      Here, we used human DSM specimens from open bladder surgeries on 27 patients to
      elucidate the mechanism by which 17beta-estradiol regulates large conductance
      voltage- and Ca2+-activated K+ (BK) channels, the most prominent K+ channels in
      human DSM We employed single BK channel recordings on inside-out excised membrane
      patches, perforated whole-cell patch-clamp on freshly isolated DSM cells, and
      isometric tension recordings on DSM-isolated strips to investigate the mechanism
      by which 17beta-estradiol activates BK channels. 17beta-Estradiol (100 nmol/L)
      rapidly increased depolarization-induced whole-cell K+ currents in DSM cells. The
      17beta-estradiol stimulatory effects on whole-cell BK currents were completely
      abolished by the selective BK channel inhibitor paxilline (1 MUmol/L), clearly
      indicating that 17beta-estradiol specifically activates BK channels. 17beta
      Estradiol also increased the frequency of ryanodine receptor-mediated transient
      BK currents. Single BK channel recordings showed that 17beta-estradiol (100
      nmol/L) significantly increased the BK channel open probability of inside-out
      excised membrane patches, revealing that 17beta-estradiol activates BK channels
      directly. 17beta-Estradiol reduced spontaneous phasic contractions of human DSM
      isolated strips in a concentration-dependent manner (100 nmol/L-1 MUmol/L), and
      this effect was blocked by paxilline (1 MUmol/L). 17beta-Estradiol (100 nmol/L)
      also reduced nerve-evoked contractions of human DSM-isolated strips.
      Collectively, our results reveal that 17beta-estradiol plays a critical role in
      regulating human DSM function through a direct nongenomic activation of BK
      channels.

PMID- 28754782
TI  - CAR T Cells Infiltrate Brain, Target Tumors.
AB  - A single dose of peripherally infused CAR T cells cleared antigen-expressing
      tumor cells in patients with glioblastoma, a 10-person trial found. However, the
      cells also triggered an immunosuppressive microenvironment, and the target
      antigen, EGFR variant III, wasn't expressed uniformly in patients' tumors.

PMID- 28754788
TI  - Action is needed to avoid NHS staffing crisis in Scotland, audit finds.

PMID- 28754789
TI  - Sex and Kidney Transplantation: Why Can't a Woman Be More Like a Man?

PMID- 28754790
TI  - The Medicare Access and CHIP Reauthorization Act: Implications for Nephrology.
AB  - In response to rising Medicare costs, Congress passed the Medicare Access and
      Children's Health Insurance Program Reauthorization Act in 2015. The law
      fundamentally changes the way that health care providers are reimbursed by
      implementing a pay for performance system that rewards providers for high-value
      health care. As of the beginning of 2017, providers will be evaluated on quality
      and in later years, cost as well. High-quality, cost-efficient providers will
      receive bonuses in reimbursement, and low-quality, expensive providers will be
      penalized financially. The Centers for Medicare and Medicaid Services will
      evaluate provider costs through episodes of care, which are currently in
      development, and alternative payment models. Although dialysis-specific
      alternative payment models have already been implemented, current models do not
      address the transition of patients from CKD to ESRD, a particularly vulnerable
      time for patients. Nephrology providers have an opportunity to develop cost
      efficient ways to care for patients during these transitions. Efforts like these,
      if successful, will help ensure that Medicare remains solvent in coming years.

PMID- 28754791
TI  - Association Analysis of the MHC in Lupus Nephritis.
AB  - Lupus nephritis (LN) is one of the most prevalent and serious complications of
      SLE, with significant effects on patient and renal survival. Although a large
      number of genetic variants associated with SLE have been identified, biomarkers
      that correlate with LN are extremely limited. In this study, we performed a
      comprehensive sequencing analysis of the whole MHC region in 1331 patients with
      LN and 1296 healthy controls and validated the independent associations in
      another 950 patients with LN and 1000 controls. We discovered five independent
      risk variants for LN within the MHC region, including HLA-DRbeta1 amino acid 11
      (Pomnibus<0.001), HLA-DQbeta1 amino acid 45 (P<0.001; odds ratio, 0.58; 95%
      confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (Pomnibus<0.001), HLA
      DPbeta1 amino acid 76 (Pomnibus<0.001), and a missense variant in PRRC2A
      (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49)
      at genome-wide significance. These data implicate aberrant peptide presentation
      by MHC classes 1 and 2 molecules and sex hormone modulation in the development of
      LN.

PMID- 28754792
TI  - Regulation of Nephron Progenitor Cell Self-Renewal by Intermediary Metabolism.
AB  - Nephron progenitor cells (NPCs) show an age-dependent capacity to balance self
      renewal with differentiation. Older NPCs (postnatal day 0) exit the progenitor
      niche at a higher rate than younger (embryonic day 13.5) NPCs do. This behavior
      is reflected in the transcript profiles of young and old NPCs. Bioenergetic
      pathways have emerged as important regulators of stem cell fate. Here, we
      investigated the mechanisms underlying this regulation in murine NPCs. Upon
      isolation and culture in NPC renewal medium, younger NPCs displayed a higher
      glycolysis rate than older NPCs. Inhibition of glycolysis enhanced nephrogenesis
      in cultured embryonic kidneys, without increasing ureteric tree branching, and
      promoted mesenchymal-to-epithelial transition in cultured isolated metanephric
      mesenchyme. Cotreatment with a canonical Wnt signaling inhibitor attenuated but
      did not entirely block the increase in nephrogenesis observed after glycolysis
      inhibition. Furthermore, inhibition of the phosphatidylinositol 3-kinase/Akt self
      renewal signaling pathway or stimulation of differentiation pathways in the NPC
      decreased glycolytic flux. Our findings suggest that glycolysis is a pivotal,
      cell-intrinsic determinant of NPC fate, with a high glycolytic flux supporting
      self-renewal and inhibition of glycolysis stimulating differentiation.

PMID- 28754793
TI  - Protecting Privacy in Large Datasets-First We Assess the Risk; Then We Fuzzy the
      Data.
AB  - Background: Privacy of information is an increasing concern with the availability
      of large amounts of data from many individuals. Even when access to data is
      heavily controlled, and the data shared with researchers contain no personal
      identifying information, there is a possibility of reidentifying individuals. To
      avoid reidentification, several anonymization protocols are available. These
      include categorizing variables into broader categories to ensure more than one
      individual in each category, such as k-anonymization, as well as protocols aimed
      at adding noise to the data. However, data custodians rarely assess
      reidentification risks.Methods: We assessed the reidentification risk of a large
      realistic dataset based on screening data from over 5 million records on 0.9
      million women in the Norwegian Cervical Cancer Screening Program, before and
      after we used old and new techniques of adding noise (fuzzification) of the
      data.Results: Categorizing date variables (applying k-anonymization)
      substantially reduced the possibility of reidentification of individuals. Adding
      a random factor, such as a fuzzy factor used here, makes it even more difficult
      to reidentify specific individuals.Conclusions: Our results show that simple
      techniques can substantially reduce the risk of reidentification.Impact: Registry
      owners and large-scale data custodians should consider estimating and if
      necessary, reducing reidentification risks before sharing large datasets. Cancer
      Epidemiol Biomarkers Prev; 26(8); 1-6. (c)2017 AACR.

PMID- 28754794
TI  - A Comparative Study on the WCRF International/University of Bristol Methodology
      for Systematic Reviews of Mechanisms Underpinning Exposure-Cancer Associations.
AB  - The World Cancer Research Fund (WCRF) International and the University of Bristol
      have developed a novel framework for providing an overview of mechanistic
      pathways and conducting a systematic literature review of the biologically
      plausible mechanisms underlying exposure-cancer associations. Two teams
      independently applied the two-stage framework on mechanisms underpinning the
      association between body fatness and breast cancer to test the framework
      feasibility and reproducibility as part of a WCRF-commissioned validation study.
      In stage I, a "hypothesis-free" approach was used to provide an overview of
      potential intermediate mechanisms between body fatness and breast cancer.
      Dissimilar rankings of potential mechanisms were observed between the two teams
      due to different applications of the framework. In stage II, a systematic review
      was conducted on the insulin-like growth factor 1 receptor (IGF1R) chosen as an
      intermediate mechanism. Although the studies included differed, both teams found
      inconclusive evidence for the body fatness-IGF1R association and modest evidence
      linking IGF1R to breast cancer, and therefore concluded that there is currently
      weak evidence for IGF1R as mechanism linking body fatness to breast cancer. The
      framework is a good starting point for conducting systematic reviews by
      integrating evidence from mechanistic studies on exposure-cancer associations. On
      the basis of our experience, we provide recommendations for future users. Cancer
      Epidemiol Biomarkers Prev; 26(11); 1583-94. (c)2017 AACR.

PMID- 28754795
TI  - Impact of Sixteen Established Pancreatic Cancer Susceptibility Loci in American
      Jews.
AB  - Background: The higher risk of pancreatic cancer in Ashkenazi Jews compared with
      non-Jews is only partially explained by the increased frequency of BRCA1 and
      BRCA2 mutations in Ashkenazi Jews.Methods: We evaluated the impact of 16
      established pancreatic cancer susceptibility loci in a case-control sample of
      American Jews, largely Ashkenazi, including 406 full-Jewish pancreatic cancer
      patients and 2,332 full-Jewish controls, genotyped as part of the Pancreatic
      Cancer Cohort and Case-Control Consortium I/II (PanScan I/II), Pancreatic Cancer
      Case-Control Consortium (PanC4), and Resource for Genetic Epidemiology Research
      on Adult Health and Aging (GERA) datasets. We compared risk in full-Jewish
      subjects with risk in part-Jewish; non-Jewish Southern European; and in the
      combined non-Jewish Eastern, Northern, Southern, and Western European (non-Jewish
      white European) subjects from the same datasets. Jewish ancestries were
      genetically identified using seeded Fast principal component analysis. Data were
      analyzed by unconditional logistic regression, and adjusted for age, sex, and
      principal components.Results: One SNP on chromosome 13q22.1 (rs9543325; OR, 1.36;
      95% confidence interval, 1.16-1.58; P = 10-4.1) was significant in full-Jews.
      Individual ORs and minor allele frequencies were similar between Jewish and non
      Jewish white European subjects. The average ORs across the 16 pancreatic cancer
      susceptibility loci for full-Jewish, full- plus part-Jewish, non-Jewish Southern
      European, and non-Jewish white European subjects were 1.25, 1.30, 1.31, and 1.26,
      respectively.Conclusions: The 16 pancreatic cancer susceptibility loci similarly
      impact Jewish and non-Jewish white European subjects, both individually and as
      summary odds.Impact: These 16 pancreatic cancer susceptibility loci likely do not
      explain the higher risk seen in Ashkenazi Jews. Cancer Epidemiol Biomarkers Prev;
      26(10); 1540-8. (c)2017 AACR.

PMID- 28754796
TI  - A Prospective Study of Chronic Inflammation in Benign Prostate Tissue and Risk of
      Prostate Cancer: Linked PCPT and SELECT Cohorts.
AB  - Background: We leveraged two trials to test the hypothesis of an inflammation
      prostate cancer link prospectively in men without indication for biopsy.Methods:
      Prostate Cancer Prevention Trial (PCPT) participants who had an end-of-study
      biopsy performed per protocol that was negative for cancer and who subsequently
      enrolled in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) were
      eligible. We selected all 100 cases and sampled 200 frequency-matched controls
      and used PCPT end-of-study biopsies as "baseline." Five men with PSA > 4 ng/mL at
      end-of-study biopsy were excluded. Tissue was located for 92 cases and 193
      controls. We visually assessed inflammation in benign tissue. We estimated ORs
      and 95% confidence intervals (CI) using logistic regression adjusting for age and
      race.Results: Mean time between biopsy and diagnosis was 5.9 years. In men
      previously in the PCPT placebo arm, 78.1% of cases (N = 41) and 68.2% of controls
      (N = 85) had at least one baseline biopsy core (~5 evaluated per man) with
      inflammation. The odds of prostate cancer (N = 41 cases) appeared to increase
      with increasing mean percentage of tissue area with inflammation, a trend that
      was statistically significant for Gleason sum <4+3 disease (N = 31 cases; vs. 0%,
      >0-<1.8% OR = 1.70, 1.8-<5.0% OR = 2.39, >=5% OR = 3.31, Ptrend = 0.047). In men
      previously in the finasteride arm, prevalence of inflammation did not differ
      between cases (76.5%; N = 51) and controls (75.0%; N = 108).Conclusions: Benign
      tissue inflammation was positively associated with prostate cancer.Impact: This
      first prospective study of men without biopsy indication supports the hypothesis
      that inflammation influences prostate cancer development. Cancer Epidemiol
      Biomarkers Prev; 26(10); 1549-57. (c)2017 AACR.

PMID- 28754797
TI  - Elastase inhibitors as potential therapies for ELANE-associated neutropenia.
AB  - Mutations in ELANE, the gene for neutrophil elastase (NE), a protease expressed
      early in neutrophil development, are the most frequent cause of cyclic (CyN) and
      severe congenital neutropenia (SCN). We hypothesized that inhibitors of NE,
      acting either by directly inhibiting enzymatic activity or as chaperones for the
      mutant protein, might be effective as therapy for CyN and SCN. We investigated
      beta-lactam-based inhibitors of human NE (Merck Research Laboratories,
      Kenilworth, NJ, USA), focusing on 1 inhibitor called MK0339, a potent, orally
      absorbed agent that had been tested in clinical trials and shown to have a
      favorable safety profile. Because fresh, primary bone marrow cells are rarely
      available in sufficient quantities for research studies, we used 3 cellular
      models: patient-derived, induced pluripotent stem cells (iPSCs); HL60 cells
      transiently expressing mutant NE; and HL60 cells with regulated expression of the
      mutant enzyme. In all 3 models, the cells expressing the mutant enzyme had
      reduced survival as measured with annexin V and FACS. Coincubation with the
      inhibitors, particularly MK0339, promoted cell survival and increased formation
      of mature neutrophils. These studies suggest that cell-permeable inhibitors of
      neutrophil elastase show promise as novel therapies for ELANE-associated
      neutropenia.

PMID- 28754798
TI  - Frontline Science: CXCR7 mediates CD14+CD16+ monocyte transmigration across the
      blood brain barrier: a potential therapeutic target for NeuroAIDS.
AB  - CD14+CD16+ monocytes transmigrate into the CNS of HIV-positive people in response
      to chemokines elevated in the brains of infected individuals, including CXCL12.
      Entry of these cells leads to viral reservoirs, neuroinflammation, and neuronal
      damage. These may eventually lead to HIV-associated neurocognitive disorders.
      Although antiretroviral therapy (ART) has significantly improved the lives of HIV
      infected people, the prevalence of cognitive deficits remains unchanged despite
      ART, still affecting >50% of infected individuals. There are no therapies to
      reduce these deficits or to prevent CNS entry of CD14+CD16+ monocytes. The goal
      of this study was to determine whether CXCR7, a receptor for CXCL12, is expressed
      on CD14+CD16+ monocytes and whether a small molecule CXCR7 antagonist (CCX771)
      can prevent CD14+CD16+ monocyte transmigration into the CNS. We showed for the
      first time that CXCR7 is on CD14+CD16+ monocytes and that it may be a therapeutic
      target to reduce their entry into the brain. We demonstrated that CD14+CD16+
      monocytes and not the more abundant CD14+CD16- monocytes or T cells transmigrate
      to low homeostatic levels of CXCL12. This may be a result of increased CXCR7 on
      CD14+CD16+ monocytes. We showed that CCX771 reduced transmigration of CD14+CD16+
      monocytes but not of CD14+CD16- monocytes from uninfected and HIV-infected
      individuals and that it reduced CXCL12-mediated chemotaxis of CD14+CD16+
      monocytes. We propose that CXCR7 is a therapeutic target on CD14+CD16+ monocytes
      to limit their CNS entry, thereby reducing neuroinflammation, neuronal damage,
      and HIV-associated neurocognitive disorders. Our data also suggest that CCX771
      may reduce CD14+CD16+ monocyte-mediated inflammation in other disorders.

PMID- 28754799
TI  - The nonreceptor protein tyrosine kinase Pyk2 promotes the turnover of monocytes
      at steady state.
AB  - Monocytes are short-lived myeloid cells that perform functions essential for
      tissue homeostasis and disease resolution. However, the cellular mechanisms
      controlling the maintenance and turnover of monocyte populations are largely
      undefined. Proline-rich tyrosine kinase 2 (Pyk2) is a nonreceptor tyrosine kinase
      that regulates numerous immune cell functions, but its role in monocytes is
      currently unknown. In this study, we sought to characterize the expression and
      function of Pyk2 in lineage-committed monocyte populations. Here, we report that
      Pyk2 protein expression is increased in the Ly6C- monocyte population. Using a
      Pyk2 knockout mouse model (Pyk2-/-), we show that Pyk2 regulates the relative
      proportion of monocyte subsets normally represented in the bone marrow (BM) at
      steady state. In support of this conclusion, a similar phenotype was observed in
      the peripheral blood and spleen. Data from reciprocal BM chimera experiments
      indicate that the alterations in monocyte populations exhibited by Pyk2-/- mice
      are due to factors intrinsic to the monocytes. Lineage-tracing of monocyte
      populations suggests that Pyk2 promotes apoptosis in BM monocytes, thereby acting
      as an important homeostatic regulator of turnover in these short-lived, innate
      immune cells.

PMID- 28754800
TI  - Frontline Science: Tim-3-mediated dysfunctional engulfment of apoptotic cells in
      SLE.
AB  - T cell Ig and mucin domain-containing molecule 3 (Tim-3) has been found to play
      important roles in autoimmune diseases, but whether Tim-3-mediated engulfment of
      apoptotic cells is involved in systemic lupus erythematosus (SLE) remains to be
      elucidated. In this study, we verified the role of human Tim-3 (hTim-3) as the
      receptor of phosphatidylserine (PS) in human embryonic kidney (HEK)293 cells,
      which initiated the engulfment of apoptotic cells. Both IgV and the mucin domain
      of Tim-3 were crucial in the phagocytosis of apoptotic cells, and there existed
      the key cytoplasmic domain for signal transduction. Alanine at 111, locating
      around the FG-CC' loop of hTim-3, was necessary for its engulfment of apoptotic
      cells. In accordance, Tim-3 on CD14+ cells negatively correlated with the
      percentage of peripheral apoptotic cells in control subjects. However, although
      Tim-3 was significantly increased on CD14+ cells in SLE patients, peripheral
      apoptotic cells remained much higher than those in control subjects. Tim-3 on
      CD14+ cells showed positive correlation with percentage of apoptotic cells and
      level of dsDNA, indicating the involvement of Tim-3 in SLE. Accordingly, soluble
      Tim-3 (sTim-3) was significantly increased in plasma of SLE patients, which might
      contribute to higher expression of a disintegrin and metalloproteinase (ADAM)-10.
      Pretreatment with both plasma from SLE patients and recombinant sTim-3 greatly
      inhibited hTim-3-initiated phagocytosis of apoptotic cells. Furthermore, anti-Tim
      3 antibody depletion of plasma from SLE patients reversed the decreased
      phagocytosis of apoptotic cells. Collectively, our data suggest that sTim-3 might
      play inhibitory roles in impaired Tim-3-mediated clearance of apoptotic cells in
      SLE.

PMID- 28754801
TI  - Subgroup analyses of the effectiveness of oral glucosamine for knee and hip
      osteoarthritis: a systematic review and individual patient data meta-analysis
      from the OA trial bank.
AB  - OBJECTIVE: To evaluate the effectiveness of oral glucosamine in subgroups of
      people with hip or knee osteoarthritis (OA) based on baseline pain severity, body
      mass index (BMI), sex, structural abnormalities and presence of inflammation
      using individual patient data. METHODS: After a systematic search of the
      literature and clinical trial registries, all randomised controlled trials (RCTs)
      evaluating the effect of any oral glucosamine substance in patients with
      clinically or radiographically defined hip or knee OA were contacted. As a
      minimum, pain, age, sex and BMI at baseline and pain as an outcome measure needed
      to be assessed. RESULTS: Of 21 eligible studies, six (n=1663) shared their trial
      data with the OA Trial Bank. Five trials (all independent of industry, n=1625)
      compared glucosamine with placebo, representing 55% of the total number of
      participants in all published placebo-controlled RCTs. Glucosamine was no better
      than placebo for pain or function at short (3 months) and long-term (24 months)
      follow-up. Glucosamine was also no better than placebo among the predefined
      subgroups. Stratification for knee OA and type of glucosamine did not alter these
      results. CONCLUSIONS: Although proposed and debated for several years, open trial
      data are not widely made available for studies of glucosamine for OA, especially
      those sponsored by industry. Currently, there is no good evidence to support the
      use of glucosamine for hip or knee OA and an absence of evidence to support
      specific consideration of glucosamine for any clinically relevant OA subgroup
      according to baseline pain severity, BMI, sex, structural abnormalities or
      presence of inflammation.

PMID- 28754802
TI  - Ultrasonography of major salivary glands compared with parotid and labial gland
      biopsy and classification criteria in patients with clinically suspected primary
      Sjogren's syndrome.
AB  - OBJECTIVE: To assess the validity of ultrasound of major salivary glands (sUS)
      compared with parotid and labial gland biopsies, sialometry, anti-SSA/Ro antibody
      status and classification criteria in patients clinically suspected with primary
      Sjogren's syndrome (pSS). METHODS: 103 consecutive outpatients with clinically
      suspected pSS underwent sUS. Parenchymal echogenicity, homogeneity, hypoechogenic
      areas, hyperechogenic reflections and clearness of salivary gland border were
      scored according to the Hocevar scoring system. Total ultrasound score was
      calculated as the sum of these domains (range 0-48). RESULTS: Absolute agreement
      between sUS and parotid (83%) and labial (79%) gland biopsy outcome was good.
      Negative sUS predicts negative parotid gland biopsy, and positive sUS predicts
      positive labial gland biopsy. Compared with the American European Consensus Group
      (AECG) classification, sUS showed an absolute agreement of 82%, sensitivity of
      71% and specificity of 92%. Compared with the American College of Rheumatology
      (ACR) classification, absolute agreement was 86%, sensitivity was 77% and
      specificity was 92%. Compared with the ACR-European League Against Rheumatism
      (EULAR) classification, absolute agreement was 80%, sensitivity was 67% and
      specificity was 94%. Positive sUS predicts classification, but negative sUS does
      not exclude classification. The combination of positive sUS with presence of anti
      SSA/Ro antibodies or negative sUS with absence of anti-SSA/Ro antibodies showed a
      high predictive value for classification as pSS or non-pSS. CONCLUSION: In our
      prospective inception cohort study derived from daily clinical practice, absolute
      agreement between sUS and salivary gland biopsies was slightly higher for parotid
      compared with labial gland biopsies. The combination of positive sUS and presence
      of anti-SSA/Ro antibodies highly predicts classification according to the AECG,
      ACR and ACR-EULAR classification criteria.

PMID- 28754803
TI  - Uric acid and incident dementia over 12 years of follow-up: a population-based
      cohort study.
AB  - OBJECTIVES: In patients with gout, maintaining too low serum uric acid (SUA)
      level with urate-lowering therapy is a concern because uric acid is thought to be
      neuroprotective. However, the relation between SUA and dementia remains debated.
      This study aimed to investigate the impact of SUA level on the incidence of
      dementia. METHODS: We assessed the longitudinal association between SUA level and
      incident dementia (Diagnostic and Statistical Manual of Mental Disorders Version
      IV (DSM-IV) criteria) in a large cohort of healthy older people from the
      community (Three-City Dijon cohort). Additionally, we investigated the relation
      between SUA level and MRI markers of brain ageing (white matter hyperintensity
      volume (WMHV), lacunes and hippocampal volume). RESULTS: The study sample
      comprised 1598 people (mean (SD) age 72.4(4.1) years, 38.3% male). During the
      13,357 person-years of follow-up (median duration: 10.1 years), dementia
      developed in 110 participants (crude incidence rate: 8.2/1000 person-years).
      After multiple adjustments, the multivariate HR with the highest (>=75th
      percentile) versus lowest SUA level was 1.79 (95% CI 1.17 to 2.73; p=0.007). The
      association was stronger with vascular or mixed dementia (HR=3.66 (95% CI 1.29 to
      10.41), p=0.015) than Alzheimer's disease (HR=1.55 (95% CI 0.92 to 2.61),
      p=0.10). There was a non-significant trend towards an association between high
      SUA level and extensive WMHV (p=0.10), a biomarker of small vessel disease, but
      not hippocampal volume (p=0.94) or lacunes (p=0.86). The association between SUA
      level and vascular or mixed dementia might be affected by interim strokes.
      CONCLUSIONS: Risk of dementia, especially vascular or mixed dementia, may be
      increased with high SUA levels in elderly people.

PMID- 28754804
TI  - Fifteen-minute consultation: Monogenic forms of diabetes with onset after age 6
      months.
AB  - Monogenic forms of diabetes (historically known as Maturity Onset Diabetes of the
      Young (MODY)) are caused by single gene mutations inherited in an autosomal
      dominant fashion that result in reduced pancreatic beta cell function. Children
      with these forms of diabetes may be misdiagnosed as having type 1 or 2 diabetes,
      which has important implications for treatment, genetic counselling, screening of
      family members and prognosis. Useful tools now exist to aid in their diagnosis
      and management. Here, we attempt to outline the clinical features that will help
      the physician make the differentiation from other diabetes subtypes.

PMID- 28754805
TI  - Retroviral insertional mutagenesis implicates E3 ubiquitin ligase RNF168 in the
      control of cell proliferation and survival.
AB  - The E3 ubiquitin ligase RNF168 is a ring finger protein that has previously been
      identified to play an important regulatory role in the repair of double-strand
      DNA breaks.  In the present study, an unbiased forward genetics functional screen
      in mouse granulocyte/ macrophage progenitor cell line FDCP1 has identified E3
      ubiquitin ligase RNF168 as a key regulator of cell survival and proliferation.
      Our data indicate that RNF168 is an important component of the mechanisms
      controlling cell fate, not only in human and mouse haematopoietic growth factor
      dependent cells, but also in the human breast epithelial cell line MCF-7. These
      observations therefore suggest that RNF168 provides a connection to key pathways
      controlling cell fate, potentially through interaction with PML nuclear bodies
      and/or epigenetic control of gene expression. Our study is the first to
      demonstrate a critical role for RNF168 in the in the mechanisms regulating cell
      proliferation and survival, in addition to its well-established role in DNA
      repair.

PMID- 28754806
TI  - Impact of balloon guide catheter on technical and clinical outcomes: a systematic
      review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Flow arrest with balloon guide catheters (BGCs) is
      becoming increasingly recognized as critical to optimizing patient outcomes for
      mechanical thrombectomy. We performed a systematic review and meta-analysis of
      the literature for studies that compared angiographic and clinical outcomes for
      patients who underwent mechanical thrombectomy with and without BGCs. MATERIALS
      AND METHODS: In April 2017 a literature search on BGC and mechanical thrombectomy
      for stroke was performed. All studies included patients treated with and without
      BGCs using modern techniques (ie, stent retrievers). Using random effects meta
      analysis, we evaluated the following outcomes: first-pass recanalization,
      Thrombolysis In Cerebral Infarction (TICI) 3 recanalization, TICI 2b/3
      recanalization, favorable outcome (modified Rankin Scale (mRS) 0-2), mortality,
      and mean number of passes and procedure time. RESULTS: Five non-randomized
      studies of 2022 patients were included (1083 BGC group and 939 non-BGC group).
      Compared with the non-BGC group, patients treated with BGCs had higher odds of
      first-pass recanalization (OR 2.05, 95% CI 1.65 to 2.55), TICI 3 (OR 2.13, 95% CI
      1.43 to 3.17), TICI 2b/3 (OR 1.54, 95% CI 1.21 to 1.97), and mRS 0-2 (OR 1.84,
      95% CI 1.52 to 2.22). BGC-treated patients also had lower odds of mortality (OR
      0.52, 95% CI 0.37 to 0.73) compared with non-BGC patients. The mean number of
      passes was significantly lower for BGC-treated patients (weighted mean difference
      -0.34, 95% CI-0.47 to -0.22). Mean procedure time was also significantly shorter
      for BGC-treated patients (weighted mean difference -7.7 min, 95% CI-9.0to -6.4).
      CONCLUSIONS: Non-randomized studies suggest that BGC use during mechanical
      thrombectomy for acute ischemic stroke is associated with superior clinical and
      angiographic outcomes. Further randomized trials are needed to confirm the
      results of this study.

PMID- 28754807
TI  - Balloon-assisted coil embolization and large stent delivery for cerebral
      aneurysms with a new generation of dual lumen balloons (Copernic 2L).
AB  - INTRODUCTION: Dual coaxial lumen balloon microcatheters through which small
      stents can be delivered have recently been described. We report a series of a new
      type of dual lumen balloon catheter with a parallel lumen design enabling
      enhanced inflation and deflation properties through which larger stents may be
      deployed, including flow diverters (FD). METHODS: All aneurysms that were treated
      with a Copernic 2L (COP2L) dual lumen balloon catheter at our institution between
      February 2014 and December 2016 were assessed. Patient demographics, aneurysm
      characteristics, clinical and angiographic follow-up, as well as adverse events
      were analyzed. RESULTS: A total of 18 aneurysms in 16 patients (14 women) were
      treated with the COP2L. Mean maximal aneurysm diameter was 6.4 mm, mean neck size
      was 3.3 mm (min 1; max 6.3), and mean aneurysm height/width was 1.1 (min 0.5; max
      2.1). The COP2L was used for balloon-remodeled coiling exclusively in 2
      aneurysms; coiling and FD stenting in 8; coiling and braided stent delivery in 3;
      coiling, braided and FD stenting in 1; and FD stenting without coiling in 4
      (stenting alone). The rate of Roy-Raymond 1 (complete occlusion) changed from 22%
      in the immediate postoperative period to 100% at 3 months (mean imaging follow-up
      8.2 months). There were three technical complications (3/16, 18.7%), including a
      perforation and two thromboembolic asymptomatic events that were rapidly
      controlled with the COP2L. There was no immediate or delayed morbidity or
      mortality (modified Rankin Scale score 0-1 in 100% of patients). CONCLUSION: The
      COP2L is a new type of dual lumen balloon catheter that may be useful for balloon
      and/or stent-assisted coiling of cerebral aneurysms. The same device can be used
      to deliver stents up to 4.5 mm and to optimize stent/wall apposition or serve as
      a life-saving tool in case of thromboembolic or hemorrhagic events. Long-term
      efficacy and safety need to be further assessed with larger case-controlled
      cohorts.

PMID- 28754808
TI  - Sex disparities in ideal cardiovascular health.
AB  - OBJECTIVE: To quantify the gap in the distribution of ideal cardiovascular health
      (CVH) between men and women accounting for comorbidities, socioeconomic and
      psychological confounding factors. METHODS: A cross-sectional analysis was
      conducted among 9012 French men and women aged 50-75 years who were participants
      of the Paris Prospective Study 3. Each of the seven metrics was defined according
      to the American Heart Association criteria, and the CVH was considered as poor (0
      or 1 ideal health metric), intermediate (2, 3 or 4 ideal health metrics) and
      ideal (5-7 ideal health metrics). The odds of intermediate and ideal CVH in women
      compared with men were estimated by multivariate polytomous logistic regression
      analysis using poor CVH as the reference category. RESULTS: The mean age was
      59.49 year (SD 6.25) and there were 38.54% of women. Though women were slightly
      older, less educated, more deprived, more often depressed, they were twice more
      often in ideal CVH than men (14.77% vs 6.84%, p<0.0001). After adjustment for
      age, deprivation score, education and depression, women were four times more
      often in ideal CVH (OR 4.01, 95% CI 3.42 to 4.69) and two times more often in
      intermediate CVH (OR 2.07, 95% CI 1.88 to 2.28) than men. CONCLUSION: The sex
      disparities in the prevalence of ideal CVH have the potential to guide sex
      specific strategies for improving CVH status in the general population. CLINICAL
      TRIAL REGISTRATION: NCT00741728;Pre-results.

PMID- 28754809
TI  - Ventricular function and vascular dimensions after Norwood and hybrid palliation
      of hypoplastic left heart syndrome.
AB  - OBJECTIVE: Norwood and hybrid procedure are two options available for initial
      palliation of patients with hypoplastic left heart syndrome (HLHS). Our study
      aimed to assess potential differences in right ventricular (RV) function and
      pulmonary artery dimensions using cardiac magnetic resonance (CMR) in survivors
      with HLHS. METHODS: 42 Norwood (mean age 2.4+/-0.8) and 44 hybrid (mean age 2.0+/
      1.0 years) patients were evaluated by CMR after stage II palliation prior to
      planned Fontan completion. Initial stage I Norwood procedure was performed using
      a modified Blalock-Taussig shunt, while the hybrid procedure consisted of
      bilateral pulmonary artery banding and arterial duct stenting. Need for
      reinterventions and subsequent outcomes were also assessed. RESULTS: Norwood
      patients had larger RV end-diastolic dimensions (91+/-23 vs 80+/-31 mL/m2,
      p=0.004) and lower heart rate (90+/-15 vs 102+/-13, p<0.001) than hybrid
      patients. Both Norwood and hybrid patients showed preserved global RV pump
      function (59+/-9 vs 59%+/-10%, p=0.91), while RV strain, strain rate and
      intraventricular synchrony were superior in the Norwood group. Pulmonary artery
      size was reduced (lower lobe index 135+/-74 vs 161+/-62 mm2/m2, p=0.02), and
      reintervention rate was significantly higher in the hybrid group whereas
      subsequent outcome did not differ significantly (p=0.24). CONCLUSIONS: Norwood
      and hybrid strategy were associated with equivalent and preserved global RV pump
      function while development of the pulmonary arteries and reintervention rate were
      superior using the Norwood approach. Impaired RV myocardial deformation as a
      potential marker of early RV dysfunction in the hybrid group may have a negative
      long-term impact in this population.

PMID- 28754810
TI  - Infective endocarditis in adults with congenital heart disease remains a lethal
      disease.
AB  - OBJECTIVE: Infective endocarditis (IE) is associated with significant morbidity
      and mortality. Patients with adult congenital heart disease (ACHD) have an
      increased risk of developing IE. The aim of this study is to describe the
      incidence, predictors of outcome and mortality associated with IE in ACHD in a
      contemporary cohort. METHODS: All episodes of IE in adults with congenital heart
      disease referred to our tertiary centre between 1999 and 2013 were included in
      the study. Patients were identified from the hospital database. The diagnosis of
      endocarditis was established according to the modified Duke criteria. The primary
      endpoint of the study was endocarditis-associated mortality. RESULTS: There were
      164 episodes of IE in 144 patients (male 102, 70.8%). Mean age at presentation
      was 32.3+/-22.7 years. Out of these, 43% had a simple, 23% a moderate and 32% a
      complex lesion. It was at least the second bout of IE in 37 episodes (23%). A
      predisposing event could be identified in only 26.2% of episodes. Surgical
      intervention during the same admission was performed in 61 episodes (37.2%).
      During a median follow-up of 6.7 years (IQR 2.9-11.4), 28 (19.4%) patients died.
      Out of these, 10 deaths were related to IE (IE mortality 6.9%). On unvariate
      regression analysis, the development of an abscess (OR: 7.23; 95% CI 1.81 to
      28.94, p<0.01) and age (OR: 1.05; 95% CI 1.01 to 1.10, p=0.03) were the only
      predictors of IE-associated mortality. There was no increase in IE cases at our
      centre during the period of the study. CONCLUSIONS: IE-associated morbidity and
      mortality in a contemporary cohort of ACHD patients is still high in the current
      era.

PMID- 28754811
TI  - Consistency of pressure injury documentation across interfacility transfers.
AB  - BACKGROUND: Hospital-acquired pressure injuries (HAPIs) are publicly reported in
      the USA and used to adjust Medicare payment to acute inpatient facilities.
      Current methods used to identify HAPIs in administrative claims rely on hospital
      reported present-on-admission (POA) data instead of prior patient health
      information. OBJECTIVE: To study the reliability of claims data for HAPIs and
      pressure injury (PI) stage by evaluating diagnostic coding agreement across
      interfacility transfers. METHODS: Using the 2012 100% Medicare Provider and
      Analysis Review file, we identified all fee-for-service acute inpatient discharge
      records with a PI diagnosis among Medicare patients 65 years and older. We then
      identified additional facility claims (eg, acute inpatient, long-stay inpatient
      or skilled nursing facility) belonging to the same patient who had either (1)
      admission within 1day of hospital discharge or (2) discharge within 1day of
      hospital admission. Multivariable logistic regression and stratified kappa
      statistics were used to measure coding agreement between transferring and
      receiving facilities in the presence or absence of a PI diagnosis at the time of
      patient transfer and PI stage category (early vs advanced). RESULTS: In our
      comparison of claims data between transferring and receiving facilities, we
      observed poor agreement in the presence or absence of a PI diagnosis at the time
      of transfer (36.3%, kappa=0.03) and poor agreement in PI stage category (74.3%,
      kappa=0.17). Among transfers with a POA PI reported by the receiving hospital,
      only 34.0% had a PI documented at the prior transferring facility. CONCLUSIONS:
      The observed discordance in PI documentation and staging between transferring and
      receiving facilities may indicate inaccuracy of HAPI identification in claims
      data. Future research should evaluate the accuracy of hospital-reported POA data
      and its impact on PI quality measurement.

PMID- 28754812
TI  - Outpatient CPOE orders discontinued due to 'erroneous entry': prospective survey
      of prescribers' explanations for errors.
AB  - BACKGROUND: Computerised prescriber order entry (CPOE) systems users often
      discontinue medications because the initial order was erroneous. OBJECTIVE: To
      elucidate error types by querying prescribers about their reasons for
      discontinuing outpatient medication orders that they had self-identified as
      erroneous. METHODS: During a nearly 3 year retrospective data collection period,
      we identified 57 972 drugs discontinued with the reason 'Error (erroneous
      entry)." Because chart reviews revealed limited information about these errors,
      we prospectively studied consecutive, discontinued erroneous orders by querying
      prescribers in near-real-time to learn more about the erroneous orders. RESULTS:
      From January 2014 to April 2014, we prospectively emailed prescribers about
      outpatient drug orders that they had discontinued due to erroneous initial order
      entry. Of 2 50 806 medication orders in these 4 months, 1133 (0.45%) of these
      were discontinued due to error. From these 1133, we emailed 542 unique
      prescribers to ask about their reason(s) for discontinuing these mediation orders
      in error. We received 312 responses (58% response rate). We categorised these
      responses using a previously published taxonomy. The top reasons for these
      discontinued erroneous orders included: medication ordered for wrong patient
      (27.8%, n=60); wrong drug ordered (18.5%, n=40); and duplicate order placed
      (14.4%, n=31). Other common discontinued erroneous orders related to drug dosage
      and formulation (eg, extended release versus not). Oxycodone (3%) was the most
      frequent drug discontinued error. CONCLUSION: Drugs are not infrequently
      discontinued 'in error.' Wrong patient and wrong drug errors constitute the
      leading types of erroneous prescriptions recognised and discontinued by
      prescribers. Data regarding erroneous medication entries represent an important
      source of intelligence about how CPOE systems are functioning and malfunctioning,
      providing important insights regarding areas for designing CPOE more safely in
      the future.

PMID- 28754813
TI  - Enhancing problem list documentation in electronic health records using two
      methods: the example of prior splenectomy.
AB  - BACKGROUND: Quality improvement professionals often choose between patient
      specific interventions, like clinical decision support (CDS), and population
      based interventions, like registries or care management. In this paper, we
      explore the synergy of these two strategies, targeting the problem of procedure
      documentation for patients with a history of splenectomy. METHODS: We developed a
      population health documentation (PHD) intervention and a CDS intervention to
      improve splenectomy documentation within our electronic health record. Rates of
      splenectomy documentation were collected before and after the implementation of
      both interventions to assess their impact on the rate of procedure documentation.
      RESULTS: Both the PHD and CDS interventions led to statistically significant
      (p<0.001) increases in the baseline rate of splenectomy documentation of 27.4
      documentations per month. During the PHD intervention, 444.7 splenectomies were
      documented per month, while 40.8 splenectomies per month were documented during
      the CDS intervention. DISCUSSION: Both approaches were successful, with the PHD
      intervention leading to a larger number of incremental procedure documentations,
      in batches, and the CDS intervention augmenting procedure documentation on an
      ongoing basis. Our results suggest that population health and CDS strategies
      complement each other and, where possible, should be used in conjunction.
      CONCLUSIONS: PHD and CDS strategies may best be used in conjunction to create a
      symbiotic relationship in which current problem and procedure documentation gaps
      are closed using PHD strategies, while new gaps are prevented through ongoing CDS
      interventions.

PMID- 28754814
TI  - The use of patient feedback by hospital boards of directors: a qualitative study
      of two NHS hospitals in England.
AB  - BACKGROUND: Although previous research suggests that different kinds of patient
      feedback are used in different ways to help improve the quality of hospital care,
      there have been no studies of the ways in which hospital boards of directors use
      feedback for this purpose. OBJECTIVES: To examine whether and how boards of
      directors of hospitals use feedback from patients to formulate strategy and to
      assure and improve the quality of care. METHODS: We undertook an in-depth
      qualitative study in two acute hospital National Health Service foundation trusts
      in England, purposively selected as contrasting examples of the collection of
      different kinds of patient feedback. We collected and analysed data from
      interviews with directors and other managers, from observation of board meetings,
      and from board papers and other documents. RESULTS: The two boards used in-depth
      qualitative feedback and quantitative feedback from surveys in different ways to
      help develop strategies, set targets for quality improvement and design specific
      quality improvement initiatives; but both boards made less subsequent use of any
      kinds of feedback to monitor their strategies or explicitly to assure the quality
      of services. DISCUSSION AND CONCLUSIONS: We have identified limitations in the
      uses of patient feedback by hospital boards that suggest that boards should
      review their current practice to ensure that they use the different kinds of
      patient feedback that are available to them more effectively to improve, monitor
      and assure the quality of care.

PMID- 28754815
TI  - Underreporting of Research Biopsies from Clinical Trials in Oncology.
AB  - Purpose: Research biopsies are frequently incorporated within clinical trials in
      oncology and are often a mandatory requirement for trial enrollment. However,
      limited information is available regarding the extent and completeness of
      research biopsy reporting.Experimental Design: We identified a cohort of
      therapeutic clinical trials where research biopsies were performed between
      January 2005 and October 2010 from an IR database at our institution. Clinical
      trial protocols were compared with the highest level of corresponding publication
      as a manuscript or registry report.Results: A total of 866 research biopsies were
      performed across 46 clinical trials, with a median of 8 patients biopsied/trial
      and 19 biopsies collected/trial. After a median follow-up time of 4.3 years from
      trial completion, 36 of 46 trials (78%) reported trial results: published
      manuscripts (n = 35), or registry report (n = 1). A total of 635 conducted
      biopsies were reported in 18 of the 46 trials (39%). Six (33%) of these 18 trials
      underreported the number of biopsies performed. Of 33 trials with mandatory
      research biopsies, 13 (39%) trials reported on these biopsies. Biopsy
      complications occurred in 8 trials [n = 39 patients, 6 grade 3/4 adverse events
      (AE)] but only 1 trial reported these. Factors associated with biopsy reporting
      included a larger number of biopsies (P <= 0.001) and serial biopsies (P <
      0.001). Twelve of 16 (75%) trials with >12 biopsies performed reported on these
      biopsies compared with only 20% (6/30) that performed <=12 biopsies.Conclusions:
      Despite ethical obligations to report research biopsies, the majority (61%) of
      trials do not report results from research biopsies. Complications are rarely
      reported in these studies. Improved reporting of results and AEs from research
      biopsies is needed. Clin Cancer Res; 23(21); 6450-7. (c)2017 AACR.

PMID- 28754816
TI  - Real-Time Genomic Profiling of Pancreatic Ductal Adenocarcinoma: Potential
      Actionability and Correlation with Clinical Phenotype.
AB  - Purpose: Molecular profiling in cancer has identified potential actionable drug
      targets that have prompted attempts to discover clinically validated biomarkers
      to guide therapeutic decision-making and enrollment to clinical trials. We
      evaluated whether comprehensive genetic analysis of patients with pancreatic
      adenocarcinoma is feasible within a clinically relevant timeframe and whether
      such analyses provide predictive and/or prognostic information along with
      identification of potential targets for therapy.Experimental Design: Archival or
      prospectively acquired FFPE samples and matched normal DNA from N = 336 patients
      with pancreatic cancer were analyzed using a hybridization capture-based, next
      generation sequencing assay designed to perform targeted deep sequencing of all
      exons and selected introns of 410 key cancer-associated genes. Demographic and
      treatment data were prospectively collected with the goal of correlating
      treatment outcomes and drug response with molecular profiles.Results: The median
      time from protocol consent to reporting of the genomic results was 45 days with a
      median time from tissue delivery of 20 days. All genetic alterations identified
      were stratified based upon prior evidence that the mutation is a predictive
      biomarker of drug response using the MSKCC OncoKB classification. Three of 225
      patients (1%) received a matched therapy based upon the sequencing
      results.Conclusions: The practical application of molecular results to guide
      individual patient treatment is currently limited in patients with pancreatic
      adenocarcinoma. Future prospective molecular profiling efforts should seek to
      incorporate routine germline genetic analysis and the identification of DNA
      profiles that predict for clinical benefit from agents that target DNA damage
      repair and or immunotherapy. Clin Cancer Res; 23(20); 6094-100. (c)2017 AACR.

PMID- 28754817
TI  - Multifaceted Role of BTLA in the Control of CD8+ T-cell Fate after Antigen
      Encounter.
AB  - Purpose: Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes
      (TIL) has shown an overall clinical response rate 40%-50% in metastatic melanoma
      patients. BTLA (B-and-T lymphocyte associated) expression on transferred CD8+
      TILs was associated with better clinical outcome. The suppressive function of the
      ITIM and ITSM motifs of BTLA is well described. Here, we sought to determine the
      functional characteristics of the CD8+BTLA+TIL subset and define the contribution
      of the Grb2 motif of BTLA in T-cell costimulation.Experimental Design: We
      determined the functional role and downstream signal of BTLA in both human CD8+
      TILs and mouse CD8+ T cells. Functional assays were used including single-cell
      analysis, reverse-phase protein array (RPPA), antigen-specific vaccination models
      with adoptively transferred TCR-transgenic T cells as well as patient-derived
      xenograft (PDX) model using immunodeficient NOD-scid IL2Rgammanull (NSG) tumor
      bearing mice treated with autologous TILs.Results: CD8+BTLA- TILs could not
      control tumor growth in vivo as well as their BTLA+ counterpart and antigen
      specific CD8+BTLA- T cells had impaired recall response to a vaccine. However,
      CD8+BTLA+ TILs displayed improved survival following the killing of a tumor
      target and heightened "serial killing" capacity. Using mutants of BTLA signaling
      motifs, we uncovered a costimulatory function mediated by Grb2 through enhancing
      the secretion of IL-2 and the activation of Src after TCR
      stimulation.Conclusions: Our data portrays BTLA as a molecule with the singular
      ability to provide both costimulatory and coinhibitory signals to activated CD8+
      T cells, resulting in extended survival, improved tumor control, and the
      development of a functional recall response. Clin Cancer Res; 23(20); 6151-64.
      (c)2017 AACR.

PMID- 28754818
TI  - TP53 Mutation and Its Prognostic Significance in Waldenstrom's Macroglobulinemia.
AB  - Purpose:TP53 is a tumor-suppressor gene that functions as a regulator influencing
      cellular responses to DNA damage, and TP53 alterations are associated with
      pejorative outcome in most B-lymphoid disorders. Little is known regarding TP53
      alteration in Waldenstrom's macroglobulinemia (WM).Experimental Design: Here, we
      have explored the incidence of TP53 alteration using Sanger sequencing and
      ultradeep-targeted sequencing in 125 WM and 10 immunoglobulin M (IgM) monoclonal
      gammopathy of undetermined significance (MGUS), along with the clinical features
      and the associated genomic landscape using single-nucleotide polymorphism array
      and mutational landscape in an integrative study.Results: Overall, we have
      identified alteration of TP53 locus including mutation, deletion, and copy
      neutral LOH in 11.2% of WM. TP53 mutation was acquired in 7.3% of patients with
      WM at diagnosis, being absent in IgM MGUS, and was highly correlated to deletion
      17p. No correlation with CXCR4 mutations was observed. Patients with TP53
      alteration had a greater number of genomic abnormalities. Importantly, WM with
      TP53 alteration had a significantly shorter overall survival, particularly in
      symptomatic WM, and independently of the international prognostic scoring system
      for Waldenstrom macroglobulinemia (IPSSWM) score. Specific treatment for WM with
      TP53 may have to be studied. Nutlin-3a-targeted p53 signaling induced
      cytotoxicity preclinically, along with new compounds such as ibrutinib, PrimaMet,
      or CP31398 that bypass p53 pathway in WM, paving the path for future treatment
      tailored options.Conclusions: Our results highlight the clinical significance of
      detection of TP53 alteration in WM to determine the prognosis of WM and guide the
      treatment choice. Clin Cancer Res; 23(20); 6325-35. (c)2017 AACR.

PMID- 28754819
TI  - Tumor Purity as an Underlying Key Factor in Glioma.
AB  - Purpose: Glioma tissues consist of not only glioma cells but also glioma
      associated nontumor cells, such as stromal cells and immune cells. These nontumor
      cells dilute the purity of glioma cells and play important roles in glioma
      biology. Currently, the implications of variation in glioma purity are not
      sufficiently clarified.Experimental Design: Here, tumor purity was inferred for
      2,249 gliomas and 29 normal brain tissues from 5 cohorts. Based on the
      transcriptomic profiling method, we classified CGGA and TCGA-RNAseq cohorts as
      the RNAseq set for discovery. Cases from TCGA-microarray, REMBRANDT, and GSE16011
      cohorts were grouped as a microarray set for validation. Tissues from the CGGA
      cohort were reviewed for histopathologic validation.Results: We found that glioma
      purity was highly associated with major clinical and molecular features. Low
      purity cases were more likely to be diagnosed as malignant entities and
      independently correlated with reduced survival time. Integrating glioma purity
      into prognostic nomogram significantly improved the predictive validity.
      Moreover, most recognized prognostic indicators were no longer significantly
      effective under different purity conditions. These results highlighted the
      clinical importance of glioma purity. Further analyses found distinct genomic
      patterns associated with glioma purity. Low purity cases were distinguished by
      enhanced immune phenotypes. Macrophages, microglia, and neutrophils were mutually
      associated and enriched in low purity gliomas, whereas only macrophages and
      neutrophils served as robust indicators for poor prognosis.Conclusions: Glioma
      purity and relevant nontumor cells within microenvironment confer important
      clinical, genomic, and biological implications, which should be fully valued for
      precise classification and clinical prediction. Clin Cancer Res; 23(20); 6279-91.
      (c)2017 AACR.

PMID- 28754820
TI  - An Integrative Scoring System for Survival Prediction Following Umbilical Cord
      Blood Transplantation in Acute Leukemia.
AB  - Purpose: Survival of acute leukemia (AL) patients following umbilical cord blood
      transplantation (UCBT) is dependent on an array of individual features.
      Integrative models for risk assessment are lacking. We sought to develop a
      scoring system for prediction of overall survival (OS) and leukemia-free survival
      (LFS) at 2 years following UCBT in AL patients.Experimental Design: The study
      cohort included 3,140 pediatric and adult AL UCBT patients from the European
      Society of Blood and Marrow Transplantation and Eurocord registries. Patients
      received single or double cord blood units. The dataset was geographically split
      into a derivation (n = 2,362, 65%) and validation set (n = 778, 35%). Top
      predictors of OS were identified using the Random Survival Forest algorithm and
      introduced into a Cox regression model, which served for the construction of the
      UCBT risk score.Results: The score includes nine variables: disease status,
      diagnosis, cell dose, age, center experience, cytomegalovirus serostatus, degree
      of HLA mismatch, previous autograft, and anti-thymocyte globulin administration.
      Over the validation set an increasing score was associated with decreasing
      probabilities for 2 years OS and LFS, ranging from 70.21% [68.89-70.71, 95%
      confidence interval (CI)] and 64.76% (64.33-65.86, 95% CI) to 14.78% (10.91
      17.41) and 18.11% (14.40-22.30), respectively. It stratified patients into six
      distinct risk groups. The score's discrimination (AUC) over multiple imputations
      of the validation set was 68.76 (68.19-69.04, range) and 65.78 (65.20-66.28) for
      2 years OS and LFS, respectively.Conclusions: The UCBT score is a simple tool for
      risk stratification of AL patients undergoing UCBT. Widespread application of the
      score will require further independent validation. Clin Cancer Res; 23(21); 6478
      86. (c)2017 AACR.

PMID- 28754821
TI  - The role of the tumour microenvironment in immunotherapy.
AB  - Recent success in immunomodulating strategies in lung cancer and melanoma has
      prompted much enthusiasm in their potential to treat other advanced solid
      malignancies. However, their applications have shown variable success and are
      even ineffective against some tumours. The efficiency of immunotherapies relies
      on an immunogenic tumour microenvironment. The current field of cancer immunology
      has focused on understanding the interaction of cancer and host immune cells to
      break the state of immune tolerance and explain how molecular patterns of
      cytokines and chemokines affect tumour progression. Here, we review our current
      knowledge of how inherent properties of tumours and their different tumour
      microenvironments affect therapeutic outcome. We also discuss insights into
      recent multimodal therapeutic approaches that target tumour immune evasion and
      suppression to restore anti-tumour immunity.

PMID- 28754822
TI  - Epigenetic research in multiple sclerosis: progress, challenges, and
      opportunities.
AB  - Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of
      the central nervous system. MS likely results from a complex interplay between
      predisposing causal gene variants (the strongest influence coming from HLA class
      II locus) and environmental risk factors such as smoking, infectious
      mononucleosis, and lack of sun exposure/vitamin D. However, little is known about
      the mechanisms underlying MS development and progression. Moreover, the clinical
      heterogeneity and variable response to treatment represent additional challenges
      to a comprehensive understanding and efficient treatment of disease. Epigenetic
      processes, such as DNA methylation and histone posttranslational modifications,
      integrate influences from the genes and the environment to regulate gene
      expression accordingly. Studying epigenetic modifications, which are stable and
      reversible, may provide an alternative approach to better understand and manage
      disease. We here aim to review findings from epigenetic studies in MS and further
      discuss the challenges and clinical opportunities arising from epigenetic
      research, many of which apply to other diseases with similar complex etiology. A
      growing body of evidence supports a role of epigenetic processes in the
      mechanisms underlying immune pathogenesis and nervous system dysfunction in MS.
      However, disparities between studies shed light on the need to consider possible
      confounders and methodological limitations for a better interpretation of the
      data. Nevertheless, translational use of epigenetics might offer new
      opportunities in epigenetic-based diagnostics and therapeutic tools for a
      personalized care of MS patients.

PMID- 28754823
TI  - Elevation of fumarase attenuates hypertension and can result from a nonsynonymous
      sequence variation or increased expression depending on rat strain.
AB  - The activity of fumarase, an enzyme in the tricarboxylic acid cycle, is lower in
      Dahl salt-sensitive SS rats compared with SS.13BN rats. SS.13BN rats have a Brown
      Norway (BN) allele of fumarase and exhibit attenuated hypertension. The SS allele
      of fumarase differs from the BN allele by a K481E sequence variation. It remains
      unknown whether higher fumarase activities can attenuate hypertension and whether
      the mechanism is relevant without the K481E variation. We developed SS-TgFh1
      transgenic rats overexpressing fumarase on the background of the SS rat.
      Hypertension was attenuated in SS-TgFh1 rats. Mean arterial pressure in SS-TgFh1
      rats was 20 mmHg lower than transgene-negative SS littermates after 12 days on a
      4% NaCl diet. Fumarase overexpression decreased H2O2, while fumarase knockdown
      increased H2O2 Ectopically expressed BN form of fumarase had higher specific
      activity than the SS form. However, sequencing of more than a dozen rat strains
      indicated most rat strains including salt-insensitive Sprague-Dawley (SD) rats
      had the SS allele of fumarase. Despite that, total fumarase enzyme activity in
      the renal medulla was still higher in SD rats than in SS rats, which was
      associated with higher expression of fumarase in SD. H2O2 can suppress the
      expression of fumarase. Renal medullary interstitial administration of fumarase
      siRNA in SD rats resulted in higher blood pressure on the high-salt diet. These
      findings indicate elevation of total fumarase activity attenuates the development
      of hypertension and can result from a nonsynonymous sequence variation in some
      rat strains and higher expression in other rat strains.

PMID- 28754824
TI  - Disclosure of patients' data to the UK Home Office must stop.

PMID- 28754825
TI  - Fluorescent imaging of protein myristoylation during cellular differentiation and
      development.
AB  - Protein post-translational modifications (PTMs) serve to give proteins new
      cellular functions and can influence spatial distribution and enzymatic activity,
      greatly enriching the complexity of the proteome. Lipidation is a PTM that
      regulates protein stability, function, and subcellular localization. To
      complement advances in proteomic identification of lipidated proteins, we have
      developed a method to image the spatial distribution of proteins that have been
      co- and post-translationally modified via the addition of myristic acid (Myr) to
      the N terminus. In this work, we use a Myr analog, 12-azidododecanoic acid (12
      ADA), to facilitate fluorescent detection of myristoylated proteins in vitro and
      in vivo. The azide moiety of 12-ADA does not react to natural biological
      chemistries, but is selectively reactive with alkyne functionalized fluorescent
      dyes. We find that the spatial distribution of myristoylated proteins varies
      dramatically between undifferentiated and differentiated muscle cells in vitro.
      Further, we demonstrate that our methodology can visualize the distribution of
      myristoylated proteins in zebrafish muscle in vivo. Selective protein labeling
      with noncanonical fatty acids, such as 12-ADA, can be used to determine the
      biological function of myristoylation and other lipid-based PTMs and can be
      extended to study deregulated protein lipidation in disease states.

PMID- 28754826
TI  - Osteopontin regulates the cross-talk between phosphatidylcholine and cholesterol
      metabolism in mouse liver.
AB  - Osteopontin (OPN) is involved in different liver pathologies in which metabolic
      dysregulation is a hallmark. Here, we investigated whether OPN could alter liver,
      and more specifically hepatocyte, lipid metabolism and the mechanism involved. In
      mice, lack of OPN enhanced cholesterol 7alpha-hydroxylase (CYP7A1) levels and
      promoted loss of phosphatidylcholine (PC) content in liver; in vivo treatment
      with recombinant (r)OPN caused opposite effects. rOPN directly decreased CYP7A1
      levels through activation of focal adhesion kinase-AKT signaling in hepatocytes.
      PC content was also decreased in OPN-deficient (OPN-KO) hepatocytes in which de
      novo FA and PC synthesis was lower, whereas cholesterol (CHOL) synthesis was
      higher, than in WT hepatocytes. In vivo inhibition of cholesterogenesis
      normalized liver PC content in OPN-KO mice, demonstrating that OPN regulates the
      cross-talk between liver CHOL and PC metabolism. Matched liver and serum samples
      showed a positive correlation between serum OPN levels and liver PC and CHOL
      concentration in nonobese patients with nonalcoholic fatty liver. In conclusion,
      OPN regulates CYP7A1 levels and the metabolic fate of liver acetyl-CoA as a
      result of CHOL and PC metabolism interplay. The results suggest that CYP7A1 is a
      main axis and that serum OPN could disrupt liver PC and CHOL metabolism,
      contributing to nonalcoholic fatty liver disease progression in nonobese
      patients.

PMID- 28754827
TI  - Organizational Update: Asia Pacific Stroke Organization.

PMID- 28754828
TI  - Readmission After Aneurysmal Subarachnoid Hemorrhage: A Nationwide Readmission
      Database Analysis.
AB  - BACKGROUND AND PURPOSE: The goal of this nationwide study is to evaluate the
      suitability of readmission as a quality indicator in the aneurysmal subarachnoid
      hemorrhage (SAH) population. METHODS: Patients with aneurysmal SAH were extracted
      from the Nationwide Readmission Database (2013). Multivariable Cox proportional
      hazard regression was used to evaluate predictors of a 30-day readmission, and
      multivariable linear regression was used to analyze the association of hospital
      readmission rates with hospital mortality rates. Predictors screened included
      patient demographics, comorbidities, severity of SAH, complications from the SAH
      hospitalization, and hospital characteristics. RESULTS: The 30-day readmission
      rate was 10.2% (n=346) among the 3387 patients evaluated, and the most common
      reasons for readmission were neurological, hydrocephalus, infectious, and venous
      thromboembolic complications. Greater number of comorbidities, increased severity
      of SAH, and discharge disposition other than to home were independent predictors
      of readmission (P<=0.03). Although hydrocephalus during the SAH hospitalization
      was associated with readmission for the same diagnosis, other readmissions were
      not associated with having sustained the same complication during the SAH
      hospitalization. Hospital mortality rate was inversely associated with hospital
      SAH volume (P=0.03) but not significantly associated with hospital readmission
      rate; hospital SAH volume was also not associated with SAH readmissions.
      CONCLUSIONS: In this national analysis, readmission was primarily attributable to
      new medical complications in patients with greater comorbidities and severity of
      SAH rather than exacerbation of complications from the SAH hospitalization.
      Additionally, hospital readmission rates did not correlate with other established
      quality metrics. Therefore, readmission may be a suboptimal quality indicator in
      the SAH population.

PMID- 28754829
TI  - Response by Barreto and Grotta to Letter Regarding Article, "Randomized,
      Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue Plasminogen
      Activator for Acute Stroke)".

PMID- 28754830
TI  - Vascular Tissue-Type Plasminogen Activator Promotes Intracranial Aneurysm
      Formation.
AB  - BACKGROUND AND PURPOSE: Although the mechanisms that contribute to intracranial
      aneurysm (IA) formation and rupture are not totally elucidated, inflammation and
      matrix remodeling are incriminated. Because tPA (tissue-type plasminogen
      activator) controls both inflammatory and matrix remodeling processes, we
      hypothesized that tPA could be involved in the pathophysiology of IA. METHODS:
      Immunofluorescence analyses of tPA and its main substrate within the aneurysmal
      wall of murine and human samples were performed. We then compared the formation
      and rupture of IAs in wild-type, tPA-deficient and type 1 plasminogen activator
      inhibitor-deficient mice subjected to a model of elastase-induced IA. The
      specific contribution of vascular versus global tPA was investigated by
      performing hepatic hydrodynamic transfection of a cDNA encoding for tPA in tPA
      deficient mice. The formation and rupture of IAs were monitored by magnetic
      resonance imaging tracking for 28 days. RESULTS: Immunofluorescence revealed
      increased expression of tPA within the aneurysmal wall. The number of aneurysms
      and their symptomatic ruptures were significantly lower in tPA-deficient than in
      wild-type mice. Conversely, they were higher in plasminogen activator inhibitor
      deficient mice. The wild-type phenotype could be restored in tPA-deficient mice
      by selectively increasing circulating levels of tPA via hepatic hydrodynamic
      transfection of a cDNA encoding for tPA. CONCLUSIONS: Altogether, this
      preclinical study demonstrates that the tPA present in the blood stream is a key
      player of the formation of IAs. Thus, tPA should be considered as a possible new
      target for the prevention of IAs formation and rupture.

PMID- 28754831
TI  - Letter by Shah Regarding Article, "Randomized, Multicenter Trial of ARTSS-2
      (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke)".

PMID- 28754832
TI  - Benchmarking Telestroke Proficiency: Page-to-Needle Time Among Neurovascular
      Fellows and Attendings.
AB  - BACKGROUND AND PURPOSE: Formal telestroke training for neurovascular fellows
      (NVFs) is necessary because of growing use of telestroke technologies in the
      management of acute ischemic stroke; yet, educational approaches and training
      benchmarks are not formalized. Time between telestroke consultant page and tissue
      type plasminogen activator administration (page-to-needle time, PTNT) can provide
      an objective measure of proficiency. We compared PTNT between NVFs and
      neurovascular attendings (NVAs) and evaluated changes in PTNT with experience.
      METHODS: We identified suspected acute ischemic stroke patients in our telestroke
      registry from July 2013 to December 2015 who received tissue-type plasminogen
      activator. Using multivariable quantile regression, we estimated the difference
      and 95% confidence interval in median PTNT between NVFs and NVAs. We also report
      the coefficient of change in PTNT over increasing number of telestroke consults.
      RESULTS: NVFs evaluated 53.7% of 618 tissue-type plasminogen activator cases over
      telestroke. NVAs had significantly shorter PTNT compared with NVFs, with a
      difference in median PTNT of -9 minutes (95% confidence interval, -12.3 to -5.7).
      This difference persisted when adjusted for relative tissue-type plasminogen
      activator contraindications. For each additional telestroke consult, PTNT
      decreased by 0.07 minutes for NVFs or NVAs (P=0.02 and <0.01, respectively).
      CONCLUSIONS: PTNT improves by ~1 minute for every 14 consults for both NVFs and
      NVAs. Our findings support the importance of integrating telestroke training into
      supervised neurovascular fellowships to increase proficiency prior to independent
      practice and suggest that PTNT can be a benchmark for tracking proficiency.

PMID- 28754833
TI  - Dolichoectasia and Small Vessel Disease in Young Patients With Transient Ischemic
      Attack and Stroke.
AB  - BACKGROUND AND PURPOSE: We evaluated whether basilar dolichoectasia is associated
      with markers of cerebral small vessel disease in younger transient ischemic
      attack and ischemic stroke patients. METHODS: We used data from the SIFAP1 study
      (Stroke in Young Fabry Patients), a large prospective, hospital-based, screening
      study for Fabry disease in young (<55 years) transient ischemic attack/stroke
      patients in whom detailed clinical data and brain MRI were obtained, and stroke
      subtyping with TOAST classification (Trial of ORG 10172 in Acute Stroke
      Treatment) was performed. RESULTS: Dolichoectasia was found in 508 of 3850
      (13.2%) of patients. Dolichoectasia was associated with older age (odds ratio per
      decade, 1.26; 95% confidence interval, 1.09-1.44), male sex (odds ratio, 1.96;
      95% confidence interval, 1.59-2.42), and hypertension (odds ratio, 1.39; 95%
      confidence interval, 1.13-1.70). Dolichoectasia was more common in patients with
      small infarctions (33.9% versus 29.8% for acute lesions, P=0.065; 29.1% versus
      16.5% for old lesions, P<0.001), infarct location in the brain stem (12.4% versus
      6.9%, P<0.001), and in white matter (27.8% versus 21.1%, P=0.001). Microbleeds
      (16.3% versus 4.7%, P=0.001), higher grades of white matter hyperintensities
      (P<0.001), and small vessel disease subtype (18.1% versus 12.4%, overall P for
      differences in TOAST (P=0.018) were more often present in patients with
      dolichoectasia. CONCLUSIONS: Dolichoectasia is associated with imaging markers of
      small vessel disease and brain stem localization of acute and old infarcts in
      younger patients with transient ischemic attack and ischemic stroke. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00414583.

PMID- 28754834
TI  - Community-Based Intervention to Improve Cardiometabolic Targets in Patients With
      Stroke: A Randomized Controlled Trial.
AB  - BACKGROUND AND PURPOSE: Many guidelines for secondary prevention of stroke focus
      on controlling cardiometabolic risk factors. We investigated the effectiveness of
      a management program for attaining cardiometabolic targets in survivors of
      stroke/transient ischemic attack. METHODS: Randomized controlled trial of
      survivors of stroke/transient ischemic attack aged >=18 years. General practices
      were randomized to usual care (control) or an intervention comprising specialist
      review of care plans and nurse education in addition to usual care. The outcome
      is attainment of pre-defined cardiometabolic targets based on Australian
      guidelines. Multivariable regression was undertaken to determine efficacy and
      identify factors associated with attaining targets. RESULTS: Overall, 283
      subjects were randomized to the intervention and 280 to controls. Although we
      found no between-group difference in overall cardiometabolic targets achieved at
      12 months, the intervention group more often achieved control of low-density
      lipoprotein cholesterol (odds ratio, 1.97; 95% confidence interval, 1.18-3.29)
      than controls. At 24 months, no between-group differences were observed.
      Medication adherence was >=80% at follow-up, but uptake of lifestyle/behavioral
      habits was poor. Older age, being male, being married/living with partner, and
      having greater functional ability or a history of diabetes mellitus were
      associated with attaining targets. CONCLUSIONS: The intervention in this largely
      negative trial only had a detectable effect on attaining target for lipids but
      not for other factors at 12 months or any factor at 24 months. This limited
      effect may be attributable to inadequate uptake of behavioral/lifestyle
      interventions, highlighting the need for new or better approaches to achieve
      meaningful behavioral change. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: ACTRN12608000166370.

PMID- 28754835
TI  - In Vivo Functional Selection Identifies Cardiotrophin-1 as a Cardiac Engraftment
      Factor for Mesenchymal Stromal Cells.
AB  - BACKGROUND: Transplantation of cells into the infarcted heart has significant
      potential to improve myocardial recovery; however, low efficacy of cell
      engraftment still limits therapeutic benefit. Here, we describe a method for the
      unbiased, in vivo selection of cytokines that improve mesenchymal stromal cell
      engraftment into the heart both in normal conditions and after myocardial
      infarction. METHODS: An arrayed library of 80 secreted factors, including most of
      the currently known interleukins and chemokines, were individually cloned into
      adeno-associated viral vectors. Pools from this library were then used for the
      batch transduction of bone marrow-derived mesenchymal stromal cells ex vivo,
      followed by intramyocardial cell administration in normal and infarcted mice.
      Three weeks after injection, vector genomes were recovered from the few
      persisting cells and identified by sequencing DNA barcodes uniquely labeling each
      of the tested cytokines. RESULTS: The most effective molecule identified by this
      competitive engraftment screening was cardiotrophin-1, a member of the
      interleukin-6 family. Intracardiac injection of mesenchymal stromal cells
      transiently preconditioned with cardiotrophin-1 preserved cardiac function and
      reduced infarct size, parallel to the persistence of the transplanted cells in
      the healing hearts for at least 2 months after injection. Engraftment of
      cardiotrophin-1-treated mesenchymal stromal cells was consequent to signal
      transducer and activator of transcription 3-mediated activation of the focal
      adhesion kinase and its associated focal adhesion complex and the consequent
      acquisition of adhesive properties by the cells. CONCLUSIONS: These results
      support the feasibility of selecting molecules in vivo for their functional
      properties with adeno-associated viral vector libraries and identify
      cardiotrophin-1 as a powerful cytokine promoting cell engraftment and thus
      improving cell therapy of the infarcted myocardium.

PMID- 28754836
TI  - Screening in larval zebrafish reveals tissue-specific distribution of fifteen
      fluorescent compounds.
AB  - The zebrafish is a prominent vertebrate model for low-cost in vivo whole organism
      screening. In our recent screening of the distribution patterns of fluorescent
      compounds in live zebrafish larvae, fifteen compounds with tissue-specific
      distributions were identified. Several compounds were observed to accumulate in
      tissues where they were reported to induce side-effects, and compounds with
      similar structures tended to be enriched in the same tissues, with minor
      differences. In particular, we found three novel red fluorescent bone-staining
      dyes: purpurin, lucidin and 3-hydroxy-morindone; purpurin can effectively label
      bones in both larval and adult zebrafish, as well as in postnatal mice, without
      significantly affecting bone mass and density. Moreover, two structurally similar
      chemotherapeutic compounds, doxorubicin and epirubicin, were observed to have
      distinct distribution preferences in zebrafish. Epirubicin maintained a
      relatively higher concentration in the liver, and performed better in inhibiting
      hepatic hyperplasia caused by the over-expression of krasG12V In total, our study
      suggests that the transparent zebrafish larvae serve as valuable tools for
      identifying tissue-specific distributions of fluorescent compounds.

PMID- 28754837
TI  - p53-independent DUX4 pathology in cell and animal models of facioscapulohumeral
      muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is a genetically dominant myopathy
      caused by mutations that disrupt repression of the normally silent DUX4 gene,
      which encodes a transcription factor that has been shown to interfere with
      myogenesis when misexpressed at very low levels in myoblasts and to cause cell
      death when overexpressed at high levels. A previous report using adeno-associated
      virus to deliver high levels of DUX4 to mouse skeletal muscle demonstrated severe
      pathology that was suppressed on a p53-knockout background, implying that DUX4
      acted through the p53 pathway. Here, we investigate the p53 dependence of DUX4
      using various in vitro and in vivo models. We find that inhibiting p53 has no
      effect on the cytoxicity of DUX4 on C2C12 myoblasts, and that expression of DUX4
      does not lead to activation of the p53 pathway. DUX4 does lead to expression of
      the classic p53 target gene Cdkn1a (p21) but in a p53-independent manner. Meta
      analysis of 5 publicly available data sets of DUX4 transcriptional profiles in
      both human and mouse cells shows no evidence of p53 activation, and further
      reveals that Cdkn1a is a mouse-specific target of DUX4. When the inducible DUX4
      mouse model is crossed onto the p53-null background, we find no suppression of
      the male-specific lethality or skin phenotypes that are characteristic of the
      DUX4 transgene, and find that primary myoblasts from this mouse are still killed
      by DUX4 expression. These data challenge the notion that the p53 pathway is
      central to the pathogenicity of DUX4.

PMID- 28754838
TI  - The chromatin remodeling BAP complex limits tumor-promoting activity of the Hippo
      pathway effector Yki to prevent neoplastic transformation in Drosophila
      epithelia.
AB  - Switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are
      mutated in many human cancers. In this article, we make use of a Drosophila
      genetic model for epithelial tumor formation to explore the tumor suppressive
      role of SWI/SNF complex proteins. Members of the BAP complex exhibit tumor
      suppressor activity in tissue overexpressing the Yorkie (Yki) proto-oncogene, but
      not in tissue overexpressing epidermal growth factor receptor (EGFR). The Brahma
      associated protein (BAP) complex has been reported to serve as a Yki-binding
      cofactor to support Yki target expression. However, we observed that depletion of
      BAP leads to ectopic expression of Yki targets both autonomously and non
      autonomously, suggesting additional indirect effects. We provide evidence that
      BAP complex depletion causes upregulation of the Wingless (Wg) and
      Decapentaplegic (Dpp) morphogens to promote tumor formation in cooperation with
      Yki.

PMID- 28754839
TI  - A Dioxygenase Catalyzes Steroid 16alpha-Hydroxylation in Steroidal Glycoalkaloid
      Biosynthesis.
AB  - Steroidal glycoalkaloids (SGAs) are toxic specialized metabolites that are found
      in the Solanaceae. Potato (Solanum tuberosum) contains the SGAs alpha-solanine
      and alpha-chaconine, while tomato (Solanum lycopersicum) contains alpha-tomatine,
      all of which are biosynthesized from cholesterol. However, although two
      cytochrome P450 monooxygenases that catalyze the 22- and 26-hydroxylation of
      cholesterol have been identified, the 16-hydroxylase remains unknown. Feeding
      with deuterium-labeled cholesterol indicated that the 16alpha- and 16beta
      hydrogen atoms of cholesterol were eliminated to form alpha-solanine and alpha
      chaconine in potato, while only the 16alpha-hydrogen atom was eliminated in alpha
      tomatine biosynthesis, suggesting that a single oxidation at C-16 takes place
      during tomato SGA biosynthesis while a two-step oxidation occurs in potato. Here,
      we show that a 2-oxoglutarate-dependent dioxygenase, designated as 16DOX, is
      involved in SGA biosynthesis. We found that the transcript of potato 16DOX
      (St16DOX) was expressed at high levels in the tuber sprouts, where large amounts
      of SGAs are accumulated. Biochemical analysis of the recombinant St16DOX protein
      revealed that St16DOX catalyzes the 16alpha-hydroxylation of hydroxycholesterols
      and that (22S)-22,26-dihydroxycholesterol was the best substrate among the nine
      compounds tested. St16DOX-silenced potato plants contained significantly lower
      levels of SGAs, and a detailed metabolite analysis revealed that they accumulated
      the glycosides of (22S)-22,26-dihydroxycholesterol. Analysis of the tomato 16DOX
      (Sl16DOX) gene gave essentially the same results. These findings clearly indicate
      that 16DOX is a steroid 16alpha-hydroxylase that functions in the SGA
      biosynthetic pathway. Furthermore, St16DOX silencing did not affect potato tuber
      yield, indicating that 16DOX may be a suitable target for controlling toxic SGA
      levels in potato.

PMID- 28754840
TI  - Overexpression of the RieskeFeS Protein Increases Electron Transport Rates and
      Biomass Yield.
AB  - In this study, we generated transgenic Arabidopsis (Arabidopsis thaliana) plants
      overexpressing the Rieske FeS protein (PetC), a component of the cytochrome b6f
      (cyt b6f) complex. Increasing the levels of this protein resulted in concomitant
      increases in the levels of cyt f (PetA) and cyt b6 (PetB), core proteins of the
      cyt b6f complex. Interestingly, an increase in the levels of proteins in both the
      photosystem I (PSI) and PSII complexes also was seen in the Rieske FeS
      overexpression plants. Although the mechanisms leading to these changes remain to
      be identified, the transgenic plants presented here provide novel tools to
      explore this. Importantly, overexpression of the Rieske FeS protein resulted in
      substantial and significant impacts on the quantum efficiency of PSI and PSII,
      electron transport, biomass, and seed yield in Arabidopsis plants. These results
      demonstrate the potential for manipulating electron transport processes to
      increase crop productivity.

PMID- 28754841
TI  - In vivo retention of 18F-AV-1451 in corticobasal syndrome.
AB  - OBJECTIVE: To study the usefulness of 18F-AV-1451 PET in patients with
      corticobasal syndrome (CBS). METHODS: We recruited 8 patients with CBS, 17
      controls, 31 patients with Alzheimer disease (AD), and 11 patients with
      progressive supranuclear palsy (PSP) from the Swedish BioFINDER study. All
      patients underwent clinical assessment, 18F-AV-1451 PET, MRI, and quantification
      of beta-amyloid pathology. A subset of participants also underwent 18F-FDG-PET.
      RESULTS: In the 8 patients with CBS, 6 had imaging findings compatible with the
      corticobasal degeneration pathology and 2 with typical AD pathology. In the 6
      patients with CBS without typical AD pathology, there were substantial retentions
      of 18F-AV-1451 in the motor cortex, corticospinal tract, and basal ganglia
      contralateral to the most affected body side. These patients could be clearly
      distinguished from patients with AD dementia or PSP using 18F-AV-1451. However,
      cortical atrophy was more widespread than the cortical retention of 18F-AV1451 in
      these CBS cases, and cortical AV-1451 uptake did not correlate with cortical
      thickness or glucose hypometabolism. These results are in sharp contrast to AD
      dementia, where 18F-AV-1451 retention was more widespread than cortical atrophy,
      and correlated well with cortical thickness and hypometabolism. CONCLUSIONS:
      Patients with CBS without typical AD pathology exhibited AV-1451 retention in the
      motor cortex, corticospinal tract, and basal ganglia contralateral to the
      affected body side, clearly different from controls and patients with AD dementia
      or PSP. However, cortical atrophy measured with MRI and decreased 18F
      fluorodeoxyglucose uptake were more widespread than 18F-AV-1451 uptake and
      probably represent earlier, yet less specific, markers of CBS. CLASSIFICATION OF
      EVIDENCE: This study provides Class III evidence that 18F-AV-1451 PET
      distinguishes between CBS and AD or PSP.

PMID- 28754842
TI  - Oral fluoroquinolones and risk of secondary pseudotumor cerebri syndrome: Nested
      case-control study.
AB  - OBJECTIVE: To quantify the risk of secondary pseudotumor cerebri syndrome (PTCS)
      with fluoroquinolones. METHODS: A case-control study of people 15-60 years of age
      from the LifeLink Database (QuintilesIMS, Parsippany, NJ) was conducted. Cases
      had the first ICD-9-CM code for benign intracranial hypertension (BIH) as well as
      having received a procedure code for an MRI or CT scan and a lumbar puncture
      within 15 days or 30 days of the BIH code. For each case, 10 controls were
      selected using density-based sampling. Current users of fluoroquinolones received
      a prescription within 15 days or 30 days of the date of the diagnosis. For the
      sensitivity analysis, risk periods for 30 and 60 days were also examined.
      Adjusted rate ratios (RRs) were computed from a conditional logistic regression
      model. RESULTS: From a cohort of 6,110,723 people, there were 339 cases of PTCS
      and 3,390 corresponding controls. In the primary analysis, the adjusted RR for
      current users of fluoroquinolones for both the 15-day and 30-day definitions were
      5.67 (95% confidence interval [CI] 2.72-11.83) and 4.15 (95% CI 2.29-7.50),
      respectively. The risk with tetracycline antibiotics was also increased, with RRs
      for 15 and 30 days of current use of 2.68 (0.89-8.11) and 3.64 (1.67-7.91),
      respectively. CONCLUSION: Our study suggests an increase in the risk of PTCS with
      current users of fluoroquinolones. Although this adverse event is rare, patients
      who experience symptoms of raised intracranial pressure including headaches,
      tinnitus, and double vision while taking fluoroquinolones should seek medical
      attention.

PMID- 28754885
TI  - Computed Tomography (CT) Findings of Pulmonary Hydatid Cysts in Children and the
      Factors Related to Cyst Rupture.
AB  - BACKGROUND The lungs are the most common site of hydatid cysts in children.
      Rupture is the main complication of cysts causing morbidity and mortality. In
      this study we aimed to comprehensively describe the CT signs for cysts and
      analyze the relationship of cyst ruptures to the diameter and location of cyst.
      MATERIAL AND METHODS A total of 145 cysts from 102 patients, aged 17 years or
      younger, who underwent a multi-detector computed tomography (MDCT) evaluation and
      had surgically proven pulmonary hydatid disease were included retrospectively.
      The CT images were analyzed for radiologic findings and signs of cyst rupture.
      RESULTS The cysts had a mean diameter of 5.45+/-3.03 cm. Most of the patients had
      a solitary cyst (70.6%). The most common lobes involved were the lower lobes
      (58.6%). Peripherally located cysts were more common than central cysts. The
      overall number of ruptured cysts was 69 (47.5%). The most common sign was the
      waterlily sign with a prevalence of 24.6%. After exclusion of cysts of 1 cm, the
      mean cyst diameter was 6.23+/-2.83 cm in the unruptured group and 5.02+/-2.80 cm
      in the complete ruptured group (p=0.020). The mean cyst diameter was 6.38+/-3.11
      cm for centrally located cysts, and 4.31+/-2.37 cm for peripherally located cysts
      (p<0.0001). CONCLUSIONS Pulmonary hydatid cysts commonly presents as solitary
      cysts with a predilection for lower lobes and the peripheral regions of the lung.
      Peripherally located cysts are more common but smaller than centrally located
      cysts. Radiologists should also be aware of atypical imaging findings of cyst
      rupture, and radiologic signs should be explored during radiologic evaluation.

PMID- 28754886
TI  - The Predictive Value of Genetic Analyses in the Diagnosis of Tetrahydrobiopterin
      (BH4)-Responsiveness in Chinese Phenylalanine Hydroxylase Deficiency Patients.
AB  - Molecular characterization of PAH deficiency has been proven essential in
      establishing treatment options. We examine the diagnostic accuracy of two genetic
      assays to predict BH4 responsiveness: to determine whether the AV sum test or
      mutation-status assessment test can obviate the need for BH4 loading in Chinese
      patients. The overall predicted response in 346 patients was 31.65% by the AV sum
      test and 25.43% by the other assay; both percentages were lower than 51.06%
      derived from loading results in 94 patients. Responders were compound
      heterozygotes with definite BH4 responsive mutations, while non-responders had
      null/null ones; some consistently with specific mutations and genotypes. The
      sensitivity and specificity of the assays were 81.1% and 92.5% for the AV sum,
      and 82.9%, 97.3% for the other. An AV sum cutoff >2 has a positive predictive
      value (PPV) of 90.9%, while the presence of at least one BH4 responsive mutation
      has a PPV of 97.1%. The two approaches showed good concordance. Our data
      confirmed that the mutation-status assessment has a higher diagnostic accuracy in
      predicting response for Chinese patients than the AV sum test. BH4-responsiveness
      may be predicted or excluded from patients' molecular characteristics to some
      extent, thus some patients may avoid the initial loading.

PMID- 28754887
TI  - Antisymmetry of oceanic eddies across the Kuroshio over a shelfbreak.
AB  - From the analysis of oceanic eddies detected in the drifter trajectories of the
      Global Drifter Program (GDP) data set, it was found that oceanic eddies are
      asymmetrically distributed across the Kuroshio in the East China Sea: predominant
      cyclonic (anticyclonic) eddies are on the western (eastern) sides of Kuroshio.
      This distribution is confirmed by high-resolution numerical modeling output as
      well. Most of these eddies are 5~20 km in radius, less than the local first
      baroclinic deformation radius, thus categorized as submesoscale. The generation
      mechanism of these submesoscale eddies is speculated to be related to the
      horizontal velocity shear of the Kuroshio when it flows northeastward along the
      shelf break in the East China Sea. The budget analysis of eddy kinetic energy
      shows that both the horizontal shear and vertical buoyancy flux are important
      energy sources for eddy generation on the two sides of Kuroshio axis. The finding
      highlights the unique feature of oceanic eddies along the western boundary
      currents.

PMID- 28754888
TI  - Gyrocardiography: A New Non-invasive Monitoring Method for the Assessment of
      Cardiac Mechanics and the Estimation of Hemodynamic Variables.
AB  - Gyrocardiography (GCG) is a new non-invasive technique for assessing heart
      motions by using a sensor of angular motion - gyroscope - attached to the skin of
      the chest. In this study, we conducted simultaneous recordings of
      electrocardiography (ECG), GCG, and echocardiography in a group of subjects
      consisting of nine healthy volunteer men. Annotation of underlying fiducial
      points in GCG is presented and compared to opening and closing points of heart
      valves measured by a pulse wave Doppler. Comparison between GCG and synchronized
      tissue Doppler imaging (TDI) data shows that the GCG signal is also capable of
      providing temporal information on the systolic and early diastolic peak
      velocities of the myocardium. Furthermore, time intervals from the ECG Q-wave to
      the maximum of the integrated GCG (angular displacement) signal and maximal
      myocardial strain curves obtained by 3D speckle tracking are correlated. We see
      GCG as a promising mechanical cardiac monitoring tool that enables quantification
      of beat-by-beat dynamics of systolic time intervals (STI) related to hemodynamic
      variables and myocardial contractility.

PMID- 28754889
TI  - Genetic and neuronal mechanisms governing the sex-specific interaction between
      sleep and sexual behaviors in Drosophila.
AB  - Animals execute one particular behavior among many others in a context-dependent
      manner, yet the mechanisms underlying such behavioral choice remain poorly
      understood. Here we studied how two fundamental behaviors, sex and sleep,
      interact at genetic and neuronal levels in Drosophila. We show that an increased
      need for sleep inhibits male sexual behavior by decreasing the activity of the
      male-specific P1 neurons that coexpress the sex determination genes fru M and
      dsx, but does not affect female sexual behavior. Further, we delineate a sex
      specific neuronal circuit wherein the P1 neurons encoding increased courtship
      drive suppressed male sleep by forming mutually excitatory connections with the
      fru M -positive sleep-controlling DN1 neurons. In addition, we find that FRUM
      regulates male courtship and sleep through distinct neural substrates. These
      studies reveal the genetic and neuronal basis underlying the sex-specific
      interaction between sleep and sexual behaviors in Drosophila, and provide
      insights into how competing behaviors are co-regulated.Genes and circuits
      involved in sleep and sexual arousal have been extensively studied in Drosophila.
      Here the authors identify the sex determination genes fruitless and doublesex,
      and a sex-specific P1-DN1 neuronal feedback that governs the interaction between
      these competing behaviors.

PMID- 28754890
TI  - DMF-MALDI: droplet based microfluidic combined to MALDI-TOF for focused peptide
      detection.
AB  - We present an automated droplet microfluidic system (DMF) to generate monitored
      nanoliter aqueous droplets in oil and their deposition on a commercial stainless
      steel plate for MALDI-TOF analysis of peptides or protein digests. We demonstrate
      that DMF-MALDI combination focuses the analyte on the MALDI plate, increasing
      considerably the homogeneity of the dried material. This results in a 30times
      enhanced MALDI-TOF MS signal for a model peptide, allowing a significant
      improvement of the detection sensitivity limit (down to few tens of attomoles).
      Moreover, positive detection can be achieved from sub-nanomolar peptides
      solutions and better overall protein sequence coverages are obtained from few
      tens attomoles of protein digest. These results make DMF-MALDI a promising
      approach for the treatment of peptides samples as well as a key component for an
      integrated approach in the proteomic field.

PMID- 28754891
TI  - Cyclin-dependent Kinase 5: Novel role of gene variants identified in ADHD.
AB  - Cortical neuronal migration and formation of filamentous actin cytoskeleton,
      needed for development, normal cell growth and differentiation, are regulated by
      the cyclin-dependent kinase 5 (Cdk5). Attention deficit hyperactivity disorder
      (ADHD) is associated with delayed maturation of the brain and hence we
      hypothesized that cdk5 may have a role in ADHD. Eight functional CDK5 gene
      variants were analyzed in 848 Indo-Caucasoid individuals including 217 families
      with ADHD probands and 250 healthy volunteers. Only three variants, rs2069454,
      rs2069456 and rs2069459, predicted to affect transcription, were found to be
      bimorphic. Significant difference in rs2069456 "AC" genotype frequency was
      noticed in the probands, more specifically in the males. Family based analysis
      revealed over transmission of rs2069454 "C" and rs2069456 "A" to the probands.
      Quantitative trait analysis exhibited association of haplotypes with inattention,
      domain specific impulsivity, and behavioral problem, though no significant
      contribution was noticed on the age of onset of ADHD. Gene variants also showed
      significant association with cognitive function and co-morbidity. Probands having
      rs2069459 "TT" showed betterment during follow up. It may be inferred from this
      pilot study that CDK5 may affect ADHD etiology, possibly by attenuating synaptic
      neurotransmission and could be a useful target for therapeutic intervention.

PMID- 28754892
TI  - A cell-based high-throughput screening assay system for inhibitor compounds of
      antigen presentation by HLA class II molecule.
AB  - A number of autoimmune diseases are associated with the genotypes of human
      leukocyte antigen class II (HLA), some of which present peptides derived from
      self-proteins, resulting in clonal expansion of self-reactive T cells. Therefore,
      selective inhibition of self-peptide loading onto such disease-associated HLA
      could ameliorate the diseases. To effectively identify such compounds, in this
      study, we established, for the first time, a cell- and 96-well microplate-based
      high-throughput screening system for inhibitors of antigen presentation. A panel
      of DRB1 genes plus DRA*01:01 gene were expressed in HEK293T cells and in 3T3
      cells, and their binding with biotinylated known self-antigen peptides was
      measured by flow cytometry. HLA-DR1 (DRB1*01:01) and DR15 (DRB1*15:01) showed a
      high affinity with myelin basic protein peptide (MBP83-98). Therefore, in 96-well
      plate wells, MBP83-99 was allowed to bind to DR1 or DR15 on 3T3 cells in
      competition with a test compound, and the HLA-bound peptide was detected by
      streptavidin-conjugated beta-galactosidase, thereby identifying inhibitor
      compounds for rheumatoid arthritis or multiple sclerosis. Our assay system has a
      potential for broad applications, including designing peptide vaccines.

PMID- 28754893
TI  - Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density
      and Membrane Curvature.
AB  - The BAR domain superfamily proteins sense or induce curvature in membranes. The
      inverse-BAR domain (I-BAR) is a BAR domain that forms a straight "zeppelin
      shaped" dimer. The mechanisms by which IRSp53 I-BAR binds to and deforms a lipid
      membrane are investigated here by all-atom molecular dynamics simulation (MD),
      binding energy analysis, and the effects of mutation experiments on filopodia on
      HeLa cells. I-BAR adopts a curved structure when crystallized, but adopts a
      flatter shape in MD. The binding of I-BAR to membrane was stabilized by ~30 salt
      bridges, consistent with experiments showing that point mutations of the
      interface residues have little effect on the binding affinity whereas multiple
      mutations have considerable effect. Salt bridge formation increases the local
      density of lipids and deforms the membrane into a concave shape. In addition, the
      point mutations that break key intra-molecular salt bridges within I-BAR reduce
      the binding affinity; this was confirmed by expressing these mutants in HeLa
      cells and observing their effects. The results indicate that the stiffness of I
      BAR is important for membrane deformation, although I-BAR does not act as a
      completely rigid template.

PMID- 28754894
TI  - A cancer stem cell model as the point of origin of cancer-associated fibroblasts
      in tumor microenvironment.
AB  - Cancer-associated fibroblasts (CAFs) are one of the most prominent cell types in
      the stromal compartment of the tumor microenvironment. CAFs support multiple
      aspects of cancer progression, including tumor initiation, invasion, and
      metastasis. The heterogeneous nature of the stromal microenvironment is
      attributed to the multiple sources from which the cells in this compartment
      originate. The present study provides the first evidence that cancer stem cells
      (CSCs) are one of the key sources of CAFs in the tumor niche. We generated CSC
      like cells by treating mouse induced pluripotent stem cells with conditioned
      medium from breast cancer cell lines. The resulting cell population expressed
      both CSC and pluripotency markers, and the sphere-forming CSC-like cells formed
      subcutaneous tumors in nude mice. Intriguingly, these CSC-like cells always
      formed heterogeneous populations surrounded by myofibroblast-like cells. Based on
      this observation, we hypothesized that CSCs could be the source of the CAFs that
      support tumor maintenance and survival. To address this hypothesis, we induced
      the differentiation of spheres and purified the myofibroblast-like cells. The
      resulting cells exhibited a CAF-like phenotype, suggesting that they had
      differentiated into the subpopulations of cells that support CSC self-renewal.
      These findings provide novel insights into the dynamic interplay between various
      microenvironmental factors and CAFs in the CSC niche.

PMID- 28754895
TI  - Neuropeptide Y prolongs non-social memory and differentially affects acquisition,
      consolidation, and retrieval of non-social and social memory in male mice.
AB  - Neuropeptide Y (NPY) and its receptors (especially Y1, Y2, and Y5) are highly
      expressed in brain regions involved in learning and memory processes.
      Accordingly, NPY was shown to modulate cognitive functions in rodents. Here, we
      investigated possible memory-enhancing effects of NPY and determined the role of
      the NPY system in the acquisition, consolidation, and retrieval of non-social and
      social memory in mice, using the object and social discrimination tests,
      respectively. Intracerebroventricular (icv) infusion of NPY (1 nmol/2 ul)
      prolonged retention of non-social (object) memory, but not of social memory. This
      effect was blocked by the Y1 receptor antagonist BIBO3304 trifluoroacetate (2
      nmol/2 ul), but not by the Y2 receptor antagonist BIIE0246 (2 nmol/2 ul). While
      icv infusion of NPY did not affect the acquisition, consolidation, and retrieval
      of non-social and social memory, icv infusion of BIBO3304 trifluoroacetate and
      BIIE0246 blocked the consolidation of non-social memory and the retrieval of both
      non-social and social memory. This study suggests that NPY has memory-enhancing
      effects in a non-social context by specifically acting on Y1 receptors. It
      further suggests that the central NPY system exerts differential effects on the
      sequential phases of non-social and social memory.

PMID- 28754896
TI  - High-throughput mutagenesis using a two-fragment PCR approach.
AB  - Site-directed scanning mutagenesis is a powerful protein engineering technique
      which allows studies of protein functionality at single amino acid resolution and
      design of stabilized proteins for structural and biophysical work. However,
      creating libraries of hundreds of mutants remains a challenging, expensive and
      time-consuming process. The efficiency of the mutagenesis step is the key for
      fast and economical generation of such libraries. PCR artefacts such as
      misannealing and tandem primer repeats are often observed in mutagenesis cloning
      and reduce the efficiency of mutagenesis. Here we present a high-throughput
      mutagenesis pipeline based on established methods that significantly reduces PCR
      artefacts. We combined a two-fragment PCR approach, in which mutagenesis primers
      are used in two separate PCR reactions, with an in vitro assembly of resulting
      fragments. We show that this approach, despite being more laborious, is a very
      efficient pipeline for the creation of large libraries of mutants.

PMID- 28754897
TI  - Reciprocal regulation of TLR2-mediated IFN-beta production by SHP2 and Gsk3beta.
AB  - Toll-like receptor 2 (TLR2) mediates the innate immune response to bacterial
      lipopeptides and peptidoglycans by stimulating the production of inflammatory
      cytokines. However, the mechanisms by which TLR2 signaling regulates type I
      interferon (IFN)-beta production are poorly understood. Here, we identified Src
      homology 2-containing protein tyrosine phosphatase 2 (SHP2) as a negative
      regulator of TLR2-induced IFN-beta production. Pharmacological inhibition or
      reduced expression of SHP2 potentiated TLR2 agonist-mediated IFN-beta
      transcription and STAT1 activation, whereas overexpression of SHP2 impaired IFN
      beta transcription and STAT1 activation. SHP2 physically associated with the
      glycogen synthase kinase 3beta (Gsk3beta) in an agonist-dependent manner.
      Gsk3beta positively regulates transcription of IFN-beta following TLR2
      stimulation by inhibiting the phosphorylation of SHP2. SHP2 inhibited the
      transcriptional activity of IRF-1 and IRF-8 at the IFN-beta promoter. Remarkably,
      IRF-1 and IRF-8 are recruited to the IFN-beta promoter in a SHP2 phosphatase
      activity-dependent manner. These findings provide insight into the mechanisms by
      which SHP2 and Gsk3beta work together to modulate TLR2-mediated IFN-beta
      production in macrophages.

PMID- 28754898
TI  - Forest understory trees can be segmented accurately within sufficiently dense
      airborne laser scanning point clouds.
AB  - Airborne laser scanning (LiDAR) point clouds over large forested areas can be
      processed to segment individual trees and subsequently extract tree-level
      information. Existing segmentation procedures typically detect more than 90% of
      overstory trees, yet they barely detect 60% of understory trees because of the
      occlusion effect of higher canopy layers. Although understory trees provide
      limited financial value, they are an essential component of ecosystem functioning
      by offering habitat for numerous wildlife species and influencing stand
      development. Here we model the occlusion effect in terms of point density. We
      estimate the fractions of points representing different canopy layers (one
      overstory and multiple understory) and also pinpoint the required density for
      reasonable tree segmentation (where accuracy plateaus). We show that at a density
      of ~170 pt/m2 understory trees can likely be segmented as accurately as overstory
      trees. Given the advancements of LiDAR sensor technology, point clouds will
      affordably reach this required density. Using modern computational approaches for
      big data, the denser point clouds can efficiently be processed to ultimately
      allow accurate remote quantification of forest resources. The methodology can
      also be adopted for other similar remote sensing or advanced imaging applications
      such as geological subsurface modelling or biomedical tissue analysis.

PMID- 28754899
TI  - Efficient and Reversible Electron Doping of Semiconductor-Enriched Single-Walled
      Carbon Nanotubes by Using Decamethylcobaltocene.
AB  - Single-walled carbon nanotubes (SWCNTs) offer great potential for field-effect
      transistors and integrated circuit applications due to their extraordinary
      electrical properties. To date, as-made SWCNT transistors are usually p-type in
      air, and it still remains challenging for realizing n-type devices. Herein, we
      present efficient and reversible electron doping of semiconductor-enriched single
      walled carbon nanotubes (s-SWCNTs) by firstly utilizing decamethylcobaltocene
      (DMC) deposited by a simple spin-coating process at room temperature as an
      electron donor. A n-type transistor behavior with high on current, large I on /I
      off ratio and excellent uniformity is obtained by surface charge transfer from
      the electron donor DMC to acceptor s-SWCNTs, which is further corroborated by the
      Raman spectra and the ab initio simulation results. The DMC dopant molecules
      could be reversibly removed by immersion in N, N-Dimethylformamide solvent,
      indicating its reversibility and providing another way to control the carrier
      concentration effectively as well as selective removal of surface dopants on
      demand. Furthermore, the n-type behaviors including threshold voltage, on
      current, field-effect mobility, contact resistances, etc. are well controllable
      by adjusting the surface doping concentration. This work paves the way to explore
      and obtain high-performance n-type nanotubes for future complementary CMOS
      circuit and system applications.

PMID- 28754900
TI  - Biodegradation of 2-hydroxyl-1,4 naphthoquinone (lawsone) by Pseudomonas
      taiwanensis LH-3 isolated from activated sludge.
AB  - 2-hydroxy-1,4 naphthoquinone (lawsone) is widely used and induces environmental
      pollutions during its production and application. In the present study, a lawsone
      degrading bacterium strain, LH-3 was successfully isolated from the activated
      sludge. Based on the 16S rRNA gene analysis, the strain LH-3 phylogenetically
      belonged to the Pseudomonas taiwanensis. It could degrade 200 mg L-1 lawsone
      completely in 9 h with an inoculum quantity of 1% (v/v). The effects of
      environmental conditions on the degradation process and the degradation pathway
      were systematically investigated. LH-3 could maintain its high degradation
      efficiency under high salt condition. The identified intermediates of salicylic
      acid, 2-hydroxy-4-oxo-chroman-2-carboxylic acid, and catechol elucidated the
      potential degradation pathway. Furthermore, the immobilized LH-3 strain cells
      prepared with alginate gel and biochar performed excellent stability in nine
      successive degradation runs. It could sucessfully survive in laboratory scale
      sequencing batch reactor and become to be the dominant species. This study
      clearly revealed that LH-3 could serve as an attractive candidate for the
      microbial remediation of lawsone-containing wastewater.

PMID- 28754901
TI  - Scheduled feeding restores memory and modulates c-Fos expression in the
      suprachiasmatic nucleus and septohippocampal complex.
AB  - Disruptions in circadian timing impair spatial memory in humans and rodents.
      Circadian-arrhythmic Siberian hamsters (Phodopus sungorus) exhibit substantial
      deficits in spatial working memory as assessed by a spontaneous alternation (SA)
      task. The present study found that daily scheduled feeding rescued spatial memory
      deficits in these arrhythmic animals. Improvements in memory persisted for at
      least 3 weeks after the arrhythmic hamsters were switched back to ad libitum
      feeding. During ad libitum feeding, locomotor activity resumed its arrhythmic
      state, but performance on the SA task varied across the day with a peak in daily
      performance that corresponded to the previous daily window of food anticipation.
      At the end of scheduled feeding, c-Fos brain mapping revealed differential gene
      expression in entrained versus arrhythmic hamsters in the suprachiasmatic nucleus
      (SCN) that paralleled changes in the medial septum and hippocampus, but not in
      other neural structures. These data show that scheduled feeding can improve
      cognitive performance when SCN timing has been compromised, possibly by
      coordinating activity in the SCN and septohippocampal pathway.

PMID- 28754902
TI  - Effect of Sodium Treatment on the Performance of Electrostatic Spray Assisted
      Vapour Deposited Copper-poor Cu(In,Ga)(S,Se) 2 Solar Cells.
AB  - In our work, eco-friendly, non-vacuum and low cost Electrostatic Spray Assisted
      Vapour Deposition (ESAVD) method has been used to produce Cu(In,Ga)(S,Se)2 (CIGS)
      solar cells. Copper (Cu) deficient (Cu/In + Ga = 0.76) CIGS films were designed
      to avoid the rather dangerous KCN treatment step for the removal of conductive
      minor phases of Cu2S/Cu2Se. A simple sodium (Na) treatment method was used to
      modify the morphology and electronic properties of the absorber and it clearly
      improved the solar cell performance. The SEM and XRD results testified a slightly
      increase of the grain size and (112) crystal orientation in the Na-incorporated
      CIGS thin films. From the Mott-schottky results, it can be seen that the
      functions of the Na treatment in our non-vacuum deposited CIGS are mainly used
      for defect passivation and reduction of charge recombination. Photovoltaic
      characteristics and j-V curve demonstrated that the dipping of CIGS films in 0.2
      M NaCl solution for 20 minutes followed by selenization at 550  degrees C under
      selenium vapor resulted in the optimum photovoltaic performance, with j sc, V oc,
      FF and eta of the optimized solar cell of 29.30 mA cm-2, 0.564 V, 65.59% and
      10.83%, respectively.

PMID- 28754903
TI  - Suppression of presbyopia progression with pirenoxine eye drops: experiments on
      rats and non-blinded, randomized clinical trial of efficacy.
AB  - Various methods can correct presbyopia, but all require devices or surgeries.
      Recently, supplements or warming devices to relieve presbyopic symptoms have been
      developed, but no eye drops have been developed. We screened certain compounds
      possibly related to lens degeneration and identified pirenoxine, which has been
      used for cataracts, as a possible new pharmacologic treatment for presbyopia. We
      first researched the anti-presbyopic activity of pirenoxine in rats. The lens
      elasticity significantly (p = 0.028) increased with exposure to tobacco smoke for
      12 days, and pirenoxine eye drops significantly (p < 0.001) suppressed lens
      hardening, which causes presbyopia in humans. In a parallel randomized controlled
      clinical study of the subjects in their fifth decade of life, the objective
      accommodative amplitude (AA) decreased significantly (p < 0.01) by 0.16 diopter
      (D) in the control group, and there was no detectable change in the treatment
      group after a 6-month treatment period, suggesting that pirenoxine eye drops
      might prevent progression of presbyopia. Subjects in their sixth decade of life,
      in whom the AA was already nearly 0 D, did not show similar results. Pirenoxine
      eye drops might be a new and the first pharmacologic treatment for preventing
      progression of presbyopia.

PMID- 28754904
TI  - Robust and accurate digital measurement for HER2 amplification in HER2 equivocal
      breast cancer diagnosis.
AB  - Currently, there are no recommended alternative assays for HER2 cases deemed
      equivocal by immunohistochemistry and fluorescent in situ hybridization. Digital
      PCR (ddPCR), a highly accurate method to determine DNA copy number, could be a
      robust alternative for clinical HER2 diagnostics. HER2 and CEP17 copy numbers
      were quantified using two ddPCR platforms (QX200 and RainDrop) in 102 samples of
      invasive breast cancers. Compared to routine assays, ddPCR gave a sensitivity and
      specificity of 82.8% and 97.3% respectively, with a kappa value of 0.833 (p <
      0.001). Moreover, the method proved to be robust as the results from two
      platforms was highly correlated (R2 = 0.91; Concordance rate = 97%; kappa =
      0.923, P < 0.001). Its performance was further tested on 114 HER2 equivocal cases
      in an independent validation cohort. 75% (21/28) of cases with HER2 amplification
      and 95% (82/86) of HER2 non-amplified case were classified as positive and
      negative by ddPCR respectively (kappa = 0.709, P < 0.001). Notably, in the HER2
      amplified cases, a lower percentage of HER2 positive cells could be related to
      the discordant results. Altogether, ddPCR is a robust alternative for clinical
      HER2 diagnostics. However, intratumoral heterogeneity of HER2 status still pose a
      challenge for HER2 analysis by ddPCR.

PMID- 28754905
TI  - A Modified Preserved Nasal and Lacrimal Flap Technique in Endoscopic
      Dacryocystorhinostomy.
AB  - Here we describe a modified preserved nasal and lacrimal mucosal flap technique
      in endonasal endoscopic dacryocystorhinostomy (EES-DCR) for patients with
      epiphora secondary to primary acquired nasolacrimal duct obstruction (PANDO) and
      evaluate its outcomes. Twenty-five patients with PANDO were retrospectively
      reviewed. Modified preserved nasal and lacrimal mucosal flap technique in EES-DCR
      was applied in all 27 eyes of 25 patients. The patients were evaluated with
      objective (anatomical patency) and subjective (symptomatic cure) success rates
      within the duration of follow-up. In the present study, all of the patients'
      surgical procedures were successful. There were 2 cases of flap dislocation from
      the rhinostomy site 1 week post-operation. After a mean follow-up of 4.9 +/- 1.8
      months, the success rate of anatomical patency was 100% (27/27) and the success
      rate of symptomatic cure was 92.6% (25/27). No significant complications occurred
      intraoperatively. We concluded that the modified preserved nasal and lacrimal
      mucosal flap technique in EES-DCR for treating PANDO is simple and safe, can
      effectively cover the bare bone around the opened sac, and provide a similar or
      even better clinical outcome compared with other routine treatment techniques
      used for this condition.

PMID- 28754906
TI  - KRAS Activation and over-expression of SIRT1/BCL6 Contributes to the Pathogenesis
      of Endometriosis and Progesterone Resistance.
AB  - Endometriosis is an inflammatory condition that is associated with progesterone
      resistance and cell proliferation, resulting in pain, infertility and pregnancy
      loss. We previously demonstrated phosphorylation of STAT3 in eutopic endometrium
      of infertile women with this disorder leading to over-expression of the oncogene
      BCL6 and stabilization of hypoxia-induced factor 1 alpha (HIF-1alpha). Here we
      report coordinated activation of KRAS and over-expression of Sirtuin 1 (SIRT1), a
      histone deacetylase and gene silencer, in the eutopic endometrium from women with
      endometriosis throughout the menstrual cycle. The mice with conditional
      activation of KRAS in the PGR positive cells reveal an increase of SIRT1
      expression in the endometrium compared to control mice. The expression of
      progesterone receptor target genes including the Indian Hedgehog pathway genes
      are significantly down-regulated in the mutant mice. SIRT1 co-localizes with BCL6
      in the nuclei of affected individuals and both proteins bind to and suppress the
      promoter of GLI1, a critical mediator of progesterone action in the Indian
      Hedgehog pathway, by ChIP analysis. In eutopic endometrium, GLI1 expression is
      reduced in women with endometriosis. Together, these data suggest that KRAS,
      SIRT1 and BCL6 are coordinately over-expressed in eutopic endometrium of women
      with endometriosis and likely participate in the pathogenesis of endometriosis.

PMID- 28754908
TI  - Interaction patterns and individual dynamics shape the way we move in synchrony.
AB  - An important open problem in Human Behaviour is to understand how coordination
      emerges in human ensembles. This problem has been seldom studied quantitatively
      in the existing literature, in contrast to situations involving dual interaction.
      Here we study motor coordination (or synchronisation) in a group of individuals
      where participants are asked to visually coordinate an oscillatory hand motion.
      We separately tested two groups of seven participants. We observed that the
      coordination level of the ensemble depends on group homogeneity, as well as on
      the pattern of visual couplings (who looked at whom). Despite the complexity of
      social interactions, we show that networks of coupled heterogeneous oscillators
      with different structures capture well the group dynamics. Our findings are
      relevant to any activity requiring the coordination of several people, as in
      music, sport or at work, and can be extended to account for other perceptual
      forms of interaction such as sound or feel.

PMID- 28754907
TI  - Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate
      trophoblast differentiation.
AB  - Trophoblast stem cells (TSCs) give rise to specialized cell types within the
      placenta. However, the regulatory mechanisms that guide trophoblast cell fate
      decisions during placenta development remain ill defined. Here we exploited ATAC
      seq and transcriptional profiling strategies to describe dynamic changes in gene
      expression and chromatin accessibility during TSC differentiation. We detect
      significantly increased chromatin accessibility at key genes upregulated as TSCs
      exit from the stem cell state. However, downregulated gene expression is not
      simply due to the loss of chromatin accessibility in proximal regions.
      Additionally, transcriptional targets recognized by the zinc finger
      transcriptional repressor Prdm1/Blimp1, an essential regulator of placenta
      development, were identified in ChIP-seq experiments. Comparisons with previously
      reported ChIP-seq datasets for primordial germ cell-like cells and E18.5 small
      intestine, combined with functional annotation analysis revealed that Blimp1 has
      broadly shared as well as cell type-specific functional activities unique to the
      trophoblast lineage. Importantly, Blimp1 not only silences TSC gene expression
      but also prevents aberrant activation of divergent developmental programmes.
      Overall the present study provides new insights into the chromatin landscape and
      Blimp1-dependent regulatory networks governing trophoblast gene expression.

PMID- 28754909
TI  - Emergence of superconductivity in doped H2O ice at high pressure.
AB  - We investigate the possibility of achieving high-temperature superconductivity in
      hydrides under pressure by inducing metallization of otherwise insulating phases
      through doping, a path previously used to render standard semiconductors
      superconducting at ambient pressure. Following this idea, we study H2O, one of
      the most abundant and well-studied substances, we identify nitrogen as the most
      likely and promising substitution/dopant. We show that for realistic levels of
      doping of a few percent, the phase X of ice becomes superconducting with a
      critical temperature of about 60 K at 150 GPa. In view of the vast number of
      hydrides that are strongly covalent bonded, but that remain insulating up to
      rather large pressures, our results open a series of new possibilities in the
      quest for novel high-temperature superconductors.

PMID- 28754910
TI  - Time trends of esophageal and gastric cancer mortality in China, 1991-2009: an
      age-period-cohort analysis.
AB  - Esophageal and gastric cancers share some risk factors. This study aimed to
      compare the long-term trends in mortality rates of esophageal and gastric cancers
      in China to provide evidence for cancer prevention and control. Mortality data
      were derived from 103 continuous points of the Disease Surveillance Points system
      during 1991-2009, stratified by gender and urban-rural locations. Age-period
      cohort models were used to disentangle the time trends of esophageal and gastric
      cancer mortality. The downward slope of the period effect for esophageal cancer
      was steeper than that for gastric cancer in rural areas. Cohort effect patterns
      were similar between esophageal and gastric cancers, with an inverse U-shape
      peaking around the late 1920s and early 1930s. A second peak, appearing around
      the 1950s, was weaker than the first but apparent in males, especially for
      esophageal cancer. The more marked changes in period effect for esophageal cancer
      in rural areas suggest esophageal cancer screening practices are effective in
      reducing mortality, and similar programs targeting gastric cancer should be
      implemented. The similarities of the cohort effects in these two cancers support
      the implication of nutrition deficiency in early childhood in the development of
      upper gastrointestinal cancer.

PMID- 28754911
TI  - Chondroitin sulfate disaccharides modified the structure and function of the
      murine gut microbiome under healthy and stressed conditions.
AB  - Chondroitin sulfate (CS) has been widely used for medical and nutraceutical
      purposes due to its roles in maintaining tissue structural integrity. We
      investigated if CS disaccharides may act as a bioactive compound and modulate gut
      microbial composition in mice. Our data show that CS disaccharides
      supplementation for 16 days significantly reduced blood LPS in the mice
      experiencing exhaustive exercise stress. CS disaccharides partially restored
      total fecal short-chain fatty acids from the level significantly repressed in
      mice under the stress. Our findings demonstrated that CS was likely butyrogenic
      and resulted in a significant increase in fecal butyrate concentration. CS
      disaccharides had a profound impact on gut microbial composition, affecting the
      abundance of 13.6% and 7.3% Operational Taxonomic Units in fecal microbial
      communities in healthy and stressed mice, respectively. CS disaccharides reduced
      the prevalence of inflammatory Proteobacteria. Together, our findings
      demonstrated that CS may ameliorate stress-induced intestinal inflammation.
      Furthermore, CS significantly increased intestinal Bacteroides acidifaciens
      population, indirectly exerting its immunomodulatory effect on the intestine. CS
      disaccharides had a significant impact on a broad range of biological pathways
      under stressed condition, such as ABC transporters, two-component systems, and
      carbohydrate metabolism. Our results will facilitate the development of CS as a
      bioactive nutraceutical.

PMID- 28754912
TI  - Genetics reveal the identity and origin of the lionfish invasion in the
      Mediterranean Sea.
AB  - Following aquarium releases, invasive lionfishes have colonized large areas of
      the Caribbean and western Atlantic, resulting in an immense ecological damage.
      The early stages of that invasion are poorly known. Indeed, a lag of time between
      the introduction and detection often preclude genetic characterization of that
      crucial phase. With elevated awareness, the recent invasion of Pterois miles was
      quickly detected in the Mediterranean Sea. We hereby show that the very first
      individuals establishing populations in the Mediterranean Sea display haplotypes
      that nest within the large genetic diversity of Red Sea individuals, thus
      indicating an invasion via the Suez Canal. We also show that only two haplotypes
      are detected in the Mediterranean Sea, suggesting that few individuals may have
      been involved in the invasion. Thus, we conclude that the Mediterranean invasion
      is the result of a movement of individuals from the Red Sea, rather than from
      other means, and that low genetic diversity does not seem to have a negative
      effect on the success and spread of lionfish into the Mediterranean Sea.

PMID- 28754913
TI  - Dynamics of plasma membrane surface related to the release of extracellular
      vesicles by mesenchymal stem cells in culture.
AB  - Extracellular vesicles (exosomes and shedding vesicles) released by mesenchymal
      stem cells (MSCs) are regarded as a storable, cell-free alternative with
      comparable therapeutic potential to their parent cells. Shedding vesicles
      originate as bulges on the cell surface but little is known about their turnover
      or how their formation can be stimulated. We have used atomic force microscopy
      (AFM) to follow the formation dynamics of bulges in living adipose tissue-derived
      MSCs. AFM images showed that, in general, MSCs present hundreds of nanosized
      protrusions on their surface with life spans of 10-20 min. Scanning electron
      microscopy confirmed those images and showed that bulges are also formed on
      filamentous processes. Extracellular vesicles deposited on the culture surface
      have comparable sizes to those of bulges showing up on the cell surface. The
      amount of protrusions on cells treated with progesterone or PDGF-BB, two
      treatments that stimulate the secretion of extracellular vesicles in MSCs, was
      evaluated by AFM. Measurements of the cross-area at 50 nm over the cell surface
      provided estimates of the amount of protrusions and showed that these values
      increased with the stimulating treatments. Our study suggests that shedding
      vesicles constitute a large population of the extracellular vesicle pool.

PMID- 28754914
TI  - Memory-type ST2+CD4+ T cells participate in the steroid-resistant pathology of
      eosinophilic pneumonia.
AB  - The lung develops an unique epithelial barrier system to protect host from
      continuous invasion of various harmful particles. Interleukin (IL-)33 released
      from epithelial cells in the lung drives the type 2 immune response by activating
      ST2- expressed immune cells in various allergic diseases. However, the
      involvement of memory-type ST2+CD4+ T cells in such lung inflammation remains
      unclear. Here we demonstrated that intratracheal administration of IL-33 resulted
      in the substantial increase of numbers of tissue-resident memory-type ST2+CD4+ T
      cells in the lung. Following enhanced production of IL-5 and IL-13, eosinophilic
      lung inflammation sequentially developed. IL-33-mediated eosinophilic lung
      inflammation was not fully developed in T cell-deficient Foxn1 nu mice and NSG
      mice. Dexamethasone treatment showed limited effects on both the cell number and
      function of memory-type ST2+CD4+ T cells. Thus our study provides novel insight
      into the pathogenesis of eosinophilic lung disease, showing that memory-type
      ST2+CD4+ T cells are involved in IL-33-induced eosinophilic inflammation and
      elicited steroid-resistance.

PMID- 28754915
TI  - Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated
      via transcriptional control with direct involvement of miR-196a/b.
AB  - Annexin A1 (ANXA1) down-regulation is an early and frequent event in the
      development of head and neck squamous cell carcinomas (HNSCC). In an attempt to
      identify the underlying mechanisms of reduced ANXA1 protein expression, this
      study investigated ANXA1 mRNA expression in HNSCC specimens by both in situ
      hybridization and RT-qPCR. Results showed a perfect concordance between the
      pattern of ANXA1 mRNA and protein detected by immunofluorescence in tumors,
      precancerous lesions and normal epithelia, reflecting that ANXA1 down-regulation
      occurs at transcriptional level. We also found that both miR-196a and miR-196b
      levels inversely correlated with ANXA1 mRNA levels in paired HNSCC tissue samples
      and patient-matched normal mucosa. In addition, endogenous levels of ANXA1 mRNA
      and protein were consistently and significantly down-regulated upon miR-196a and
      miR-196b over-expression in various HNSCC-derived cell lines. The direct
      interaction of both mature miR-196a and miR-196b was further confirmed by
      transfection with Anxa1 3'UTR constructs. Combined bioinformatics and functional
      analysis of ANXA1 promoter activity contributed to identify key regions and
      potential mediators of ANXA1 transcriptional control. This study unveils that, in
      addition to miR-196a, miR-196b also directly targets ANXA1 in HNSCC.

PMID- 28754916
TI  - Self-Powered Pressure Sensor with fully encapsulated 3D printed wavy substrate
      and highly-aligned piezoelectric fibers array.
AB  - Near-field electrospinning (NFES) is capable of precisely deposit one-dimensional
      (1D) or two-dimensional (2D) highly aligned micro/nano fibers (NMFs) by
      electrically discharged a polymer solution. In this paper, a new integration of
      three-dimensional (3D) architectures of NFES electrospun polyvinylidene fluoride
      (PVDF) NMFs with the 3D printed topologically tailored substrate are demonstrated
      in a direct-write and in-situ poled manner, called wavy- substrate self-powered
      sensors (WSS). The fabrication steps are composed of the additive manufacture of
      3D printed flexible and sinusoidal wavy substrate, metallization and NFES
      electrospun fibers in the 3D topology. This 3D architecture is capable of greatly
      enhancing the piezoelectric output. Finally, the proposed piezoelectrically
      integrated 3D architecture is applied to the self-powered sensors such as foot
      pressure measurement, human motion monitoring and finger-induced power
      generation. The proposed technique demonstrates the advancement of existing
      electrospinning technologies in constructing 3D structures and several promising
      applications for biomedical and wearable electronics.

PMID- 28754917
TI  - Integrated regulatory network reveals the early salt tolerance mechanism of
      Populus euphratica.
AB  - Salinization is one of the major factors that threaten the existence of plants
      worldwide. Populus euphratica has been deemed to be a promising candidate for
      stress response research because of its high capacity to tolerate extreme salt
      stress. We carried out a genome-wide transcriptome analysis to identify the
      differentially expressed genes (DEGs) response to salt shock and elucidate the
      early salt tolerance mechanisms in P. euphratica. Both hierarchical clustering
      and DEG analysis demonstrated a predominant variation from time-course rather
      than NaCl intensity within 24 hours salt shock. Among the identified 1,678 salt
      responsive DEGs, 74.1% (1,244) have not been reported before. We further created
      an integrated regulatory gene network of the salt response in P. euphratica by
      combining DEGs, transcription factors (TFs), Helitrons, miRNAs and their targets.
      The prominent pathways in this network are plant hormone transduction, starch and
      sucrose metabolism, RNA transport, protein processing in endoplasmic reticulum,
      etc. In addition, the network indicates calcium-related genes play key roles in
      P. euphratica response to salt shock. These results illustrated an overview of
      the systematic molecular response in P. euphratica under different intensities of
      salt shock and revealed the complex regulatory mechanism.

PMID- 28754918
TI  - Activation of TGF-beta signaling induces cell death via the unfolded protein
      response in Fuchs endothelial corneal dystrophy.
AB  - Fuchs endothelial corneal dystrophy (FECD) is a slowly progressive bilateral
      disease of corneal endothelium in which accumulation of extracellular matrix
      (ECM) and loss of corneal endothelial cells (CECs) are phenotypic features. The
      corneal endothelium maintains corneal transparency by regulating water hydration;
      consequently, corneal endothelial dysfunction causes serious vision loss. The
      only therapy for corneal haziness due to corneal endothelial diseases, including
      FECD, is corneal transplantation using donor corneas, and no pharmaceutical
      treatment is available. We provide evidence that the expression levels of
      transforming growth factor-beta (TGF-beta) isoforms and TGF-beta receptors are
      high in the corneal endothelium of patients with FECD. A cell model based on
      patients with FECD shows that TGF-beta signaling induced a chronic overload of
      ECM proteins to the endoplasmic reticulum (ER), thereby enhancing the formation
      of unfolded protein and triggering the intrinsic apoptotic pathway through the
      unfolded protein response (UPR). We propose that inhibition of TGF-beta signaling
      may represent a novel therapeutic target that suppresses cell loss as well as the
      accumulation of ECM in FECD.

PMID- 28754919
TI  - Pre-therapy liver transcriptome landscape in Indian and French patients with
      severe alcoholic hepatitis and steroid responsiveness.
AB  - Patients with severe alcoholic hepatitis (SAH) not responding to glucocorticoid
      therapy have higher mortality, though they do not differ in their baseline
      clinical characteristics and prognostic scores from those who respond to therapy.
      We hypothesized that the baseline hepatic gene expression differs between
      responders (R) and non-responders (NR). Baseline liver transcriptome was compared
      between R and NR in Indian (16 each) and French (5 NR, 3 R) patients with SAH.
      There were differentially expressed genes (DEGs) between NR and R, in Indian
      (1106 over-expressed, 96 under-expressed genes) and French patients (65 over
      expressed, 142 under-expressed genes). Indian NR had features of hepatocyte
      senescence and French NR exhibited under-expression of genes involved in cell
      division, indicating a central defect in the capacity of hepatocytes for self
      renewal in both populations. Markers of hepatic progenitor cell proliferation
      were either very few (Indian patients) or absent (French patients). No DEGs were
      enriched in inflammatory pathways and there were no differences in nuclear
      receptor subfamily 3 group C member 1 (NR3C1) transcript expression and splicing
      between NR and R. Our results reveal that baseline hepatic transcriptome is
      reflective of subsequent glucocorticoid non-response and indicate impaired
      regenerative potential of the liver as an underlying phenomenon in NR.

PMID- 28754920
TI  - Usefulness of Different Pathological Scores to Assess Healing of the Mucosa in
      Inflammatory Bowel Diseases: A Real Life Study.
AB  - The concept of remission for patients with inflammatory bowel diseases has
      recently evolved, and should also include histological healing of the mucosa,
      difficult to evaluate since there is no agreement on pathological scores and
      those available are quite complex to use in the daily routine. We evaluated the
      possible usefulness of a simplified pathological score to assess histological
      healing of the mucosa in inflammatory bowel diseases patients compared with four
      commonly proposed pathological scores. Slides from 24 patients (12 Crohn's
      disease, 12 ulcerative colitis, age range 24-62 years), pre- and post-treatment
      with biological agents and displaying endoscopic remission were assessed by two
      pathologists. Pre- and post-treatment results and the time employed to calculate
      the various scores were obtained. All scores were useful to document highly
      significant post-treatment decreases of histological activity. However, the
      simplified score needed significant less time to be calculated for each slide,
      had high inter-rater agreement, and avoided subjectivity from the pathologists.
      The simplified score is easy to calculate and seems apt to document histological
      healing of the mucosa, in a manner similar to the more complex scores. It remains
      to be established whether this score could simplify the daily routinary practice
      in this context.

PMID- 28754921
TI  - Evaluation of two lead malaria transmission blocking vaccine candidate antibodies
      in natural parasite-vector combinations.
AB  - Transmission blocking vaccines (TBV) which aim to control malaria by inhibiting
      human-to-mosquito transmission show considerable promise though their utility
      against naturally circulating parasites remains unknown. The efficacy of two lead
      candidates targeting Pfs25 and Pfs230 antigens to prevent onwards transmission of
      naturally occurring parasites to a local mosquito strain is assessed using direct
      membrane feeding assays and murine antibodies in Burkina Faso. The transmission
      blocking activity of both candidates depends on the level of parasite exposure
      (as assessed by the mean number of oocysts in control mosquitoes) and antibody
      titers. A mathematical framework is devised to allow the efficacy of different
      candidates to be directly compared and determine the minimal antibody titers
      required to halt transmission in different settings. The increased efficacy with
      diminishing parasite exposure indicates that the efficacy of vaccines targeting
      either Pfs25 or Pfs230 may increase as malaria transmission declines. This has
      important implications for late-stage candidate selection and assessing how they
      can support the drive for malaria elimination.

PMID- 28754922
TI  - ShadowY: a dark yellow fluorescent protein for FLIM-based FRET measurement.
AB  - Fluorescence lifetime imaging microscopy (FLIM)-based Forster resonance energy
      transfer (FRET) measurement (FLIM-FRET) is one of the powerful methods for
      imaging of intracellular protein activities such as protein-protein interactions
      and conformational changes. Here, using saturation mutagenesis, we developed a
      dark yellow fluorescent protein named ShadowY that can serve as an acceptor for
      FLIM-FRET. ShadowY is spectrally similar to the previously reported dark YFP but
      has a much smaller quantum yield, greater extinction coefficient, and superior
      folding property. When ShadowY was paired with mEGFP or a Clover mutant
      (CloverT153M/F223R) and applied to a single-molecule FRET sensor to monitor a
      light-dependent conformational change of the light-oxygen-voltage domain 2 (LOV2)
      in HeLa cells, we observed a large FRET signal change with low cell-to-cell
      variability, allowing for precise measurement of individual cell responses. In
      addition, an application of ShadowY to a separate-type Ras FRET sensor revealed
      an EGF-dependent large FRET signal increase. Thus, ShadowY in combination with
      mEGFP or CloverT153M/F223R is a promising FLIM-FRET acceptor.

PMID- 28754923
TI  - Tauroursodeoxycholic acid enhances the development of porcine embryos derived
      from in vitro-matured oocytes and evaporatively dried spermatozoa.
AB  - Evaporative drying (ED) is an alternative technique for long-term preservation of
      mammalian sperm, which does not require liquid nitrogen or freeze-drying
      equipment, but offers advantages for storage and shipping at ambient temperature
      and low cost. However, the development of zygotes generated from these sperms was
      poor. Here, we demonstrated that the supplementation of tauroursodeoxycholic acid
      (TUDCA), an endogenous bile acid, during embryo culture improved the
      developmental competency of embryos derived from in vitro matured pig oocytes
      injected intracytoplasmically with boar ED spermatozoa by reducing the production
      of reactive oxygen species, the DNA degradation and fragmentation, and the
      expression of apoptosis-related gene Bax and Bak, and by increasing the
      transcription of anti-apoptosis gene Bcl-XL and Bcl-2. Furthermore, TUDCA
      treatment promoted the blastocyst quality manifested by the total cell numbers
      and the ratio of inner cell mass. Taken together, our data suggest that
      evaporative drying would be a potentially useful method for the routine
      preservation of boar sperm in combination with further optimization of
      subsequently embryo culture conditions.

PMID- 28754924
TI  - Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein
      family.
AB  - The emergence of genes implicated across multiple comorbid neurologic disorders
      allows to identify shared underlying molecular pathways. Recently, investigation
      of patients with diverse neurologic disorders found TANC1 and TANC2 as possible
      candidate disease genes. While the TANC proteins have been reported as
      postsynaptic scaffolds influencing synaptic spines and excitatory synapse
      strength, their molecular functions remain unknown. Here, we conducted a
      comprehensive in silico analysis of the TANC protein family to characterize their
      molecular role and understand possible neurobiological consequences of their
      disruption. The known Ankyrin and tetratricopeptide repeat (TPR) domains have
      been modeled. The newly predicted N-terminal ATPase domain may function as a
      regulated molecular switch for downstream signaling. Several putative conserved
      protein binding motifs allowed to extend the TANC interaction network.
      Interestingly, we highlighted connections with different signaling pathways
      converging to modulate neuronal activity. Beyond a known role for TANC family
      members in the glutamate receptor pathway, they seem linked to planar cell
      polarity signaling, Hippo pathway, and cilium assembly. This suggests an
      important role in neuron projection, extension and differentiation.

PMID- 28754925
TI  - Monitoring diffuse volcanic degassing during volcanic unrests: the case of Campi
      Flegrei (Italy).
AB  - In volcanoes with active hydrothermal systems, diffuse CO2 degassing may
      constitute the primary mode of volcanic degassing. The monitoring of CO2
      emissions can provide important clues in understanding the evolution of volcanic
      activity especially at calderas where the interpretation of unrest signals is
      often complex. Here, we report eighteen years of CO2 fluxes from the soil at
      Solfatara of Pozzuoli, located in the restless Campi Flegrei caldera. The entire
      dataset, one of the largest of diffuse CO2 degassing ever produced, is made
      available for the scientific community. We show that, from 2003 to 2016, the area
      releasing deep-sourced CO2 tripled its extent. This expansion was accompanied by
      an increase of the background CO2 flux, over most of the surveyed area (1.4 km2),
      with increased contributions from non-biogenic source. Concurrently, the amount
      of diffusively released CO2 increased up to values typical of persistently
      degassing active volcanoes (up to 3000 t d-1). These variations are consistent
      with the increase in the flux of magmatic fluids injected into the hydrothermal
      system, which cause pressure increase and, in turn, condensation within the vapor
      plume feeding the Solfatara emission.

PMID- 28754926
TI  - Videourodynamic Studies of Women with Voiding Dysfunction.
AB  - This retrospective study is aimed to present videourodynamic findings of women
      with symptoms of voiding dysfunction in a medical center. Of 1914 women, the
      diagnoses included bladder outlet obstruction (BOO, n = 810, 42.3%), bladder
      dysfunction (n = 1,048, 54.8%) and normal tracings (n = 56, 2.9%). Anatomic BOO
      (n = 49) included cystocele (n = 19) and urethral stricture (n = 30). Common
      functional BOOs included dysfunctional voiding (n = 325, 17.0%) and poor
      relaxation of the external sphincter (n = 336, 17.6%). Common bladder dysfunction
      subtypes included detrusor underactivity (n = 337, 17.6%), detrusor hyperactivity
      with impaired contractility (n = 231, 12.1%), and bladder oversensitivity (n =
      325, 17.0%). Receiver operating characteristic (ROC) analysis were performed, and
      the following optimum cutoff values were determined: (1) voiding detrusor
      pressure at a maximum flow rate (Pdet.Qmax) = 30 cmH2O for differentiating BOO
      from bladder dysfunction and normal tracings, with an ROC area of 0.78; (2) the
      Abrams-Griffiths number = 30 for differentiating anatomic from functional BOO,
      with an ROC area of 0.66; (3) post-void residual = 200 mL for differentiating
      bladder neck dysfunction from the other BOOs, with an ROC area of 0.69; (4)
      Pdet.Qmax = 30 cmH2O for differentiating dysfunctional voiding from poor
      relaxation of the external sphincter with an ROC area of 0.93. The above findings
      can be used as initial guide for management of female BOO.

PMID- 28754927
TI  - Perfluoroalkyl substances in human bone: concentrations in bones and effects on
      bone cell differentiation.
AB  - Perfluoroalkyl substances (PFAS), including two most commonly studied compounds
      perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are widely
      distributed environmental pollutants, used extensively earlier. Due to their
      toxicological effects the use of PFAS is now regulated. Based on earlier studies
      on PFOA's distribution in bone and bone marrow in mice, we investigated PFAS
      levels and their possible link to bone microarchitecture of human femoral bone
      samples (n = 18). Soft tissue and bone biopsies were also taken from a 49-year
      old female cadaver for PFAS analyses. We also studied how PFOA exposure affects
      differentiation of human osteoblasts and osteoclasts. PFAS were detectable from
      all dry bone and bone marrow samples, PFOS and PFOA being the most prominent. In
      cadaver biopsies, lungs and liver contained the highest concentrations of PFAS,
      whereas PFAS were absent in bone marrow. Perfluorononanoic acid (PFNA) was
      present in the bones, PFOA and PFOS were absent. In vitro results showed no
      disturbance in osteogenic differentiation after PFOA exposure, but in
      osteoclasts, lower concentrations led to increased resorption, which eventually
      dropped to zero after increase in PFOA concentration. In conclusion, PFAS are
      present in bone and have the potential to affect human bone cells partly at
      environmentally relevant concentrations.

PMID- 28754928
TI  - Probing microtubules polarity in mitotic spindles in situ using Interferometric
      Second Harmonic Generation Microscopy.
AB  - The polarity of microtubules is thought to be involved in spindle assembly,
      cytokinesis or active molecular transport. However, its exact role remains poorly
      understood, mainly because of the challenge to measure microtubule polarity in
      intact cells. We report here the use of fast Interferometric Second Harmonic
      Generation microscopy to study the polarity of microtubules forming the mitotic
      spindles in a zebrafish embryo. This technique provides a powerful tool to study
      mitotic spindle formation and may be directly transferable for investigating the
      kinetics and function of microtubule polarity in other aspects of subcellular
      motility or in native tissues.

PMID- 28754929
TI  - Training-induced dynamics of accuracy and precision in human motor control.
AB  - The study investigated the dynamic changes in accuracy and precision during a
      simple oral and digital motor task involving a controlled and a ballistic force.
      Eighteen healthy participants participated in four experimental sessions during
      which they performed one hundred trials of targeting a controlled (low/high hold
      force) and a ballistic force during an oral and a digital motor task (OMT and
      DMT). Accuracy and precision across one hundred trials were calculated and
      subjected to segmented linear regression analysis. Repeated performance of
      controlled forces show a significant dynamic change in accuracy during initial
      stage of targeting high hold forces during OMT and a significant dynamic change
      in both accuracy and precision during final stage of targeting high hold forces
      during DMT. Repeated performance of ballistic force showed a significant dynamic
      change in both accuracy and precision during final stage of targeting high hold
      force forces during OMT and a significant dynamic change in accuracy during the
      initial stages of targeting high hold force during the DMT. The findings indicate
      a subtle degree of dissociation between accuracy and precision in terms of
      dynamic modulation of forces due to repeated performance of both OMT and DMT.

PMID- 28754930
TI  - The versatility of boron in biological target engagement.
AB  - Boron-containing molecules have been extensively used for the purposes of
      chemical sensing, biological probe development and drug discovery. Due to boron's
      empty p orbital, it can coordinate to heteroatoms such as oxygen and nitrogen.
      This reversible covalent mode of interaction has led to the use of boron as bait
      for nucleophilic residues in disease-associated proteins, culminating in the
      approval of new therapeutics that work by covalent mechanisms. Our analysis of a
      wide range of covalent inhibitors with electrophilic groups suggests that boron
      is a unique electrophile in its chameleonic ability to engage protein targets.
      Here we review boron's interactions with a range of protein side-chain residues
      and reveal that boron's properties are nuanced and arise from its uncommon
      coordination preferences. These mechanistic and structural insights should serve
      as a guide for the development of selective boron-based bioactive molecules.

PMID- 28754931
TI  - Scalable and uniform 1D nanoparticles by synchronous polymerization,
      crystallization and self-assembly.
AB  - The preparation of well-defined nanoparticles based on soft matter, using
      solution-processing techniques on a commercially viable scale, is a major
      challenge of widespread importance. Self-assembly of block copolymers in solvents
      that selectively solvate one of the segments provides a promising route to core
      corona nanoparticles (micelles) with a wide range of potential uses.
      Nevertheless, significant limitations to this approach also exist. For example,
      the solution processing of block copolymers generally follows a separate
      synthesis step and is normally performed at high dilution. Moreover, non
      spherical micelles-which are promising for many applications-are generally
      difficult to access, samples are polydisperse and precise dimensional control is
      not possible. Here we demonstrate the formation of platelet and cylindrical
      micelles at concentrations up to 25% solids via a one-pot approach-starting from
      monomers-that combines polymerization-induced and crystallization-driven self
      assembly. We also show that performing the procedure in the presence of small
      seed micelles allows the scalable formation of low dispersity samples of
      cylindrical micelles of controlled length up to three micrometres.

PMID- 28754932
TI  - Unified biomimetic assembly of voacalgine A and bipleiophylline via divergent
      oxidative couplings.
AB  - Bipleiophylline is a highly complex monoterpene indole alkaloid composed of two
      pleiocarpamine units anchored on an aromatic spacer platform. The synthesis of
      bipleiophylline is considered as a mountain to climb by the organic chemistry
      community. Here, a unified oxidative coupling protocol between indole derivatives
      and 2,3-dihydroxybenzoic acid, mediated by silver oxide, has been developed to
      produce the core of bipleiophylline. This method also allows the independent
      preparation of benzofuro[2,3-b]indolenine and isochromano[3,4-b]indolenine
      scaffolds, depending only on the nature of the aromatic platform used. The
      procedure has been applied to simple indole derivatives and to more challenging
      monoterpene indole alkaloids, thereby furnishing natural-product-like structures.
      The use of scarce pleiocarpamine as the starting indole allows the first
      syntheses of bipleiophylline and of its biosynthetic precursor, voacalgine A. The
      structure of the latter has been reassigned in the course of our investigations
      by 2D NMR and displays an isochromano[3,4-b]indolenine motif instead of a
      benzofuro[2,3-b]indolenine.

PMID- 28754933
TI  - Retraction: Transferring electrons to water.
AB  - This corrects the article DOI: 10.1038/nchem.768.

PMID- 28754934
TI  - Correction.
AB  - This corrects the article DOI: 10.1038/nchem.2787.

PMID- 28754935
TI  - Meitnerium in tribute.

PMID- 28754936
TI  - Photosynthesis: Nature's power switching station.

PMID- 28754937
TI  - Retraction: Charge transfer to solvent identified using dark channel fluorescence
      yield L-edge spectroscopy.
AB  - This corrects the article DOI: 10.1038/nchem.807.

PMID- 28754938
TI  - Cytosolic delivery: Just passing through.

PMID- 28754939
TI  - Catalytic diversity in self-propagating peptide assemblies.
AB  - The protein-only infectious agents known as prions exist within cellular matrices
      as populations of assembled polypeptide phases ranging from particles to amyloid
      fibres. These phases appear to undergo Darwinian-like selection and propagation,
      yet remarkably little is known about their accessible chemical and biological
      functions. Here we construct simple peptides that assemble into well-defined
      amyloid phases and define paracrystalline surfaces able to catalyse specific
      enantioselective chemical reactions. Structural adjustments of individual amino
      acid residues predictably control both the assembled crystalline order and their
      accessible catalytic repertoire. Notably, the density and proximity of the
      extended arrays of enantioselective catalytic sites achieve template-directed
      polymerization of new polymers. These diverse amyloid templates can now be
      extended as dynamic self-propagating templates for the construction of even more
      complex functional materials.

PMID- 28754940
TI  - A device that operates within a self-assembled 3D DNA crystal.
AB  - Structural DNA nanotechnology finds applications in numerous areas, but the
      construction of objects, 2D and 3D crystalline lattices and devices is prominent
      among them. Each of these components has been developed individually, and most of
      them have been combined in pairs. However, to date there are no reports of
      independent devices contained within 3D crystals. Here we report a three-state 3D
      device whereby we change the colour of the crystals by diffusing strands that
      contain dyes in or out of the crystals through the mother-liquor component of the
      system. Each colouring strand is designed to pair with an extended triangle
      strand by Watson-Crick base pairing. The arm that contains the dyes is quite
      flexible, but it is possible to establish the presence of the duplex proximal to
      the triangle by X-ray crystallography. We modelled the transition between the red
      and blue states through a simple kinetic model.

PMID- 28754941
TI  - 101 libations.

PMID- 28754942
TI  - Macromolecular metamorphosis via stimulus-induced transformations of polymer
      architecture.
AB  - Macromolecular architecture plays a pivotal role in determining the properties of
      polymers. When designing polymers for specific applications, it is not only the
      size of a macromolecule that must be considered, but also its shape. In most
      cases, the topology of a polymer is a static feature that is inalterable once
      synthesized. Using reversible-covalent chemistry to prompt the disconnection of
      chemical bonds and the formation of new linkages in situ, we report polymers that
      undergo dramatic topological transformations via a process we term macromolecular
      metamorphosis. Utilizing this technique, a linear amphiphilic block copolymer or
      hyperbranched polymer undergoes 'metamorphosis' into comb, star and hydrophobic
      block copolymer architectures. This approach was extended to include a
      macroscopic gel which transitioned from a densely and covalently crosslinked
      network to one with larger distances between the covalent crosslinks when heated.
      These architectural transformations present an entirely new approach to 'smart'
      materials.

PMID- 28754943
TI  - Design of multi-phase dynamic chemical networks.
AB  - Template-directed polymerization reactions enable the accurate storage and
      processing of nature's biopolymer information. This mutualistic relationship of
      nucleic acids and proteins, a network known as life's central dogma, is now
      marvellously complex, and the progressive steps necessary for creating the
      initial sequence and chain-length-specific polymer templates are lost to time.
      Here we design and construct dynamic polymerization networks that exploit
      metastable prion cross-beta phases. Mixed-phase environments have been used for
      constructing synthetic polymers, but these dynamic phases emerge naturally from
      the growing peptide oligomers and create environments suitable both to nucleate
      assembly and select for ordered templates. The resulting templates direct the
      amplification of a phase containing only chain-length-specific peptide-like
      oligomers. Such multi-phase biopolymer dynamics reveal pathways for the
      emergence, self-selection and amplification of chain-length- and possibly
      sequence-specific biopolymers.

PMID- 28754944
TI  - Cytosolic antibody delivery by lipid-sensitive endosomolytic peptide.
AB  - One of the major obstacles in intracellular targeting using antibodies is their
      limited release from endosomes into the cytosol. Here we report an approach to
      deliver proteins, which include antibodies, into cells by using endosomolytic
      peptides derived from the cationic and membrane-lytic spider venom peptide M
      lycotoxin. The delivery peptides were developed by introducing one or two
      glutamic acid residues into the hydrophobic face. One peptide with the
      substitution of leucine by glutamic acid (L17E) was shown to enable a marked
      cytosolic liberation of antibodies (immunoglobulins G (IgGs)) from endosomes. The
      predominant membrane-perturbation mechanism of this peptide is the preferential
      disruption of negatively charged membranes (endosomal membranes) over neutral
      membranes (plasma membranes), and the endosomolytic peptide promotes the uptake
      by inducing macropinocytosis. The fidelity of this approach was confirmed through
      the intracellular delivery of a ribosome-inactivation protein (saporin), Cre
      recombinase and IgG delivery, which resulted in a specific labelling of the
      cytosolic proteins and subsequent suppression of the glucocorticoid receptor
      mediated transcription. We also demonstrate the L17E-mediated cytosolic delivery
      of exosome-encapsulated proteins.

PMID- 28754945
TI  - MoS2 monolayer catalyst doped with isolated Co atoms for the hydrodeoxygenation
      reaction.
AB  - The conversion of oxygen-rich biomass into hydrocarbon fuels requires efficient
      hydrodeoxygenation catalysts during the upgrading process. However, traditionally
      prepared CoMoS2 catalysts, although efficient for hydrodesulfurization, are not
      appropriate due to their poor activity, sulfur loss and rapid deactivation at
      elevated temperature. Here, we report the synthesis of MoS2 monolayer sheets
      decorated with isolated Co atoms that bond covalently to sulfur vacancies on the
      basal planes that, when compared with conventionally prepared samples, exhibit
      superior activity, selectivity and stability for the hydrodeoxygenation of 4
      methylphenol to toluene. This higher activity allows the reaction temperature to
      be reduced from the typically used 300  degrees C to 180  degrees C and thus
      allows the catalysis to proceed without sulfur loss and deactivation.
      Experimental analysis and density functional theory calculations reveal a large
      number of sites at the interface between the Co and Mo atoms on the MoS2 basal
      surface and we ascribe the higher activity to the presence of sulfur vacancies
      that are created local to the observed Co-S-Mo interfacial sites.

PMID- 28754946
TI  - Single-molecule spectroscopy of LHCSR1 protein dynamics identifies two distinct
      states responsible for multi-timescale photosynthetic photoprotection.
AB  - In oxygenic photosynthesis, light harvesting is regulated to safely dissipate
      excess energy and prevent the formation of harmful photoproducts. Regulation is
      known to be necessary for fitness, but the molecular mechanisms are not
      understood. One challenge has been that ensemble experiments average over active
      and dissipative behaviours, preventing identification of distinct states. Here,
      we use single-molecule spectroscopy to uncover the photoprotective states and
      dynamics of the light-harvesting complex stress-related 1 (LHCSR1) protein, which
      is responsible for dissipation in green algae and moss. We discover the existence
      of two dissipative states. We find that one of these states is activated by pH
      and the other by carotenoid composition, and that distinct protein dynamics
      regulate these states. Together, these two states enable the organism to respond
      to two types of intermittency in solar intensity-step changes (clouds and
      shadows) and ramp changes (sunrise), respectively. Our findings reveal key
      control mechanisms underlying photoprotective dissipation, with implications for
      increasing biomass yields and developing robust solar energy devices.

PMID- 28754947
TI  - Addendum: Activating lattice oxygen redox reactions in metal oxides to catalyse
      oxygen evolution.
AB  - This corrects the article DOI: 10.1038/nchem.2695.

PMID- 28754948
TI  - Parameterization of phosphine ligands demonstrates enhancement of nickel
      catalysis via remote steric effects.
AB  - The field of Ni-catalysed cross-coupling has seen rapid recent growth because of
      the low cost of Ni, its earth abundance, and its ability to promote unique cross
      coupling reactions. Whereas advances in the related field of Pd-catalysed cross
      coupling have been driven by ligand design, the development of ligands
      specifically for Ni has received minimal attention. Here, we disclose a class of
      phosphines that enable the Ni-catalysed Csp3 Suzuki coupling of acetals with
      boronic acids to generate benzylic ethers, a reaction that failed with known
      ligands for Ni and designer phosphines for Pd. Using parameters to quantify
      phosphine steric and electronic properties together with regression statistical
      analysis, we identify a model for ligand success. The study suggests that
      effective phosphines feature remote steric hindrance, a concept that could guide
      future ligand design tailored to Ni. Our analysis also reveals that two classic
      descriptors for ligand steric environment-cone angle and % buried volume-are not
      equivalent, despite their treatment in the literature.

PMID- 28754949
TI  - Cell-permeable nanobodies for targeted immunolabelling and antigen manipulation
      in living cells.
AB  - Functional antibody delivery in living cells would enable the labelling and
      manipulation of intracellular antigens, which constitutes a long-thought goal in
      cell biology and medicine. Here we present a modular strategy to create
      functional cell-permeable nanobodies capable of targeted labelling and
      manipulation of intracellular antigens in living cells. The cell-permeable
      nanobodies are formed by the site-specific attachment of intracellularly stable
      (or cleavable) cyclic arginine-rich cell-penetrating peptides to camelid-derived
      single-chain VHH antibody fragments. We used this strategy for the non-endocytic
      delivery of two recombinant nanobodies into living cells, which enabled the
      relocalization of the polymerase clamp PCNA (proliferating cell nuclear antigen)
      and tumour suppressor p53 to the nucleolus, and thereby allowed the detection of
      protein-protein interactions that involve these two proteins in living cells.
      Furthermore, cell-permeable nanobodies permitted the co-transport of
      therapeutically relevant proteins, such as Mecp2, into the cells. This technology
      constitutes a major step in the labelling, delivery and targeted manipulation of
      intracellular antigens. Ultimately, this approach opens the door towards
      immunostaining in living cells and the expansion of immunotherapies to
      intracellular antigen targets.

PMID- 28754950
TI  - Development of hydroxybenzoic-based platforms as a solution to deliver dietary
      antioxidants to mitochondria.
AB  - Oxidative stress and mitochondrial dysfunction have been associated with
      metabolic and age-related diseases. Thus, the prevention of mitochondrial
      oxidative damage is nowadays a recognized pharmacological strategy to delay
      disease progression. Epidemiological studies suggested an association between the
      consumption of polyphenol-rich diet and the prevention of different pathologies,
      including diseases with a mitochondrial etiology. The development of
      mitochondrial-targeted antioxidants based on dietary antioxidants may decrease
      mitochondrial oxidative damage. Herein, we report the design and synthesis of two
      new mitochondriotropic antioxidants based on hydroxybenzoic acids (AntiOxBENs).
      The results obtained showed that the novel antioxidants are accumulated inside
      rat liver mitochondria driven by the organelle transmembrane electric potential
      and prevented lipid peroxidation, exhibiting low toxicity. Some of the observed
      effects on mitochondrial bioenergetics resulted from an increase of proton
      leakage through the mitochondrial inner membrane. The new derivatives present a
      higher lipophilicity than the parent compounds (protocatechuic and gallic acids)
      and similar antioxidant and iron chelating properties. AntiOxBENs are valid
      mitochondriotropic antioxidant prototypes, which can be optimized and used in a
      next future as drug candidates to prevent or slow mitochondrial oxidative stress
      associated to several pathologies.

PMID- 28754951
TI  - Mass spectrometry-based determination of Kallikrein-related peptidase 7 (KLK7)
      cleavage preferences and subsite dependency.
AB  - The cleavage preferences of Kallikrein-related peptidase 7 (KLK7) have previously
      been delineated using synthetic peptide libraries of fixed length, or single
      protein chains and have suggested that KLK7 exerts a chymotryptic-like cleavage
      preference. Due to the short length of the peptides utilised, only a limited
      number of subsites have however been assessed. To determine the subsite
      preferences of KLK7 in a global setting, we used a mass spectrometry (MS)-based
      in-depth proteomics approach that utilises human proteome-derived peptide
      libraries of varying length, termed Proteomic Identification of protease Cleavage
      Sites (PICS). Consistent with previous findings, KLK7 was found to exert
      chymotryptic-like cleavage preferences. KLK7 subsite preferences were also
      characterised in the P2-P2' region, demonstrating a preference for hydrophobic
      residues in the non-prime and hydrophilic residues in the prime subsites.
      Interestingly, single catalytic triad mutant KLK7 (mKLK7; S195A) also showed
      residual catalytic activity (kcat/KM = 7.93 * 102 s-1M-1). Catalytic inactivity
      of KLK7 was however achieved by additional mutation in this region (D102N). In
      addition to characterising the cleavage preferences of KLK7, our data thereby
      also suggests that the use of double catalytic triad mutants should be employed
      as more appropriate negative controls in future investigations of KLK7,
      especially when highly sensitive MS-based approaches are employed.

PMID- 28754952
TI  - Mycobacterial DNA-binding protein 1 is critical for long term survival of
      Mycobacterium smegmatis and simultaneously coordinates cellular functions.
AB  - Bacteria can proliferate perpetually without ageing, but they also face
      conditions where they must persist. Mycobacteria can survive for a long period.
      This state appears during mycobacterial diseases such as tuberculosis and
      leprosy, which are chronic and develop after long-term persistent infections.
      However, the fundamental mechanisms of the long-term living of mycobacteria are
      unknown. Every Mycobacterium species expresses Mycobacterial DNA-binding protein
      1 (MDP1), a histone-like nucleoid associated protein. Mycobacterium smegmatis is
      a saprophytic fast grower and used as a model of mycobacterial persistence, since
      it shares the characteristics of the long-term survival observed in pathogenic
      mycobacteria. Here we show that MDP1-deficient M. smegmatis dies more rapidly
      than the parental strain after entering stationary phase. Proteomic analyses
      revealed 21 upregulated proteins with more than 3-fold in MDP1-deficient strain,
      including DnaA, a replication initiator, NDH, a NADH dehydrogenase that catalyzes
      downhill electron transfer, Fas1, a critical fatty acid synthase, and
      antioxidants such as AhpC and KatG. Biochemical analyses showed elevated levels
      of DNA and ATP syntheses, a decreased NADH/NAD+ ratio, and a loss of resistance
      to oxidative stress in the MDP1-knockout strain. This study suggests the
      importance of MDP1-dependent simultaneous control of the cellular functions in
      the long-term survival of mycobacteria.

PMID- 28754953
TI  - Genetically engineered rice endogenous 5-enolpyruvoylshikimate-3-phosphate
      synthase (epsps) transgene alters phenology and fitness of crop-wild hybrid
      offspring.
AB  - Genetically engineered (GE) rice endogenous epsps (5-enolpyruvoylshikimate-3
      phosphate synthase) gene overexpressing EPSPS can increase glyphosate herbicide
      resistance of cultivated rice. This type of epsps transgene can enhance the
      fecundity of rice crop-weed hybrid offspring in the absence of glyphosate,
      stimulating great concerns over undesired environmental impacts of transgene flow
      to populations of wild relatives. Here, we report the substantial alteration of
      phenology and fitness traits in F1-F3 crop-wild hybrid descendants derived from
      crosses between an epsps GE rice line and two endangered wild rice (Oryza
      rufipogon) populations, based on the common-garden field experiments. Under the
      glyphosate-free condition, transgenic hybrid lineages showed significantly
      earlier tillering and flowering, as well as increased fecundity and overwintering
      survival/regeneration abilities. In addition, a negative correlation was observed
      between the contents of endogenous EPSPS of wild, weedy, and cultivated rice
      parents and fitness differences caused by the incorporation of the epsps
      transgene. Namely, a lower level of endogenous EPSPS in the transgene-recipient
      populations displayed a more pronounced enhancement in fitness. The altered
      phenology and enhanced fitness of crop-wild hybrid offspring by the epsps
      transgene may cause unwanted environmental consequences when this type of
      glyphosate-resistance transgene introgressed into wild rice populations through
      gene flow.

PMID- 28754954
TI  - Improvement of Total Etching Dentin Bonding with Subpressure.
AB  - This study aimed to investigate the effects of subpressure on the bond properties
      of total-etching adhesive to dentin. Thirty-six caries-free premolars were
      sectioned parallel to the occlusal plane and randomly divided into four groups (n
      = 9): a control group (C, no treatment) and three subpressure groups, which were
      treated under 0.8, 0.6 or 0.4 bar after applying adhesives, named S8, S6 and S4,
      respectively. Afterward, resin was bonded to the dentin surface, and 27 beams
      (1.0 mm * 1.0 mm) of each group were sectioned. One was selected to observe the
      bonding interface from each group by SEM. Each group was divided into two
      subgroups (n = 13): 24 hours of water storage (I) and 10,000 thermocycling (A).
      The microtensile bond strength (MUTBS), failure modes and nanoleakage expression
      were evaluated. SEM results showed that the subpressure groups had longer and
      denser resin tags. The MUTBS of the subpressure groups was higher than that of
      the control group (p < 0.05). The subpressure groups were dominated by mixed
      failure, whereas main interfacial failure appeared in group C. The subpressure
      groups showed less silver deposition than the control group (p < 0.05). The
      subpressure technique may remarkably improve bonding strength and decrease
      nanoleakage on total-etching bonding.

PMID- 28754955
TI  - Isotopic analyses suggest mammoth and plant in the diet of the oldest
      anatomically modern humans from far southeast Europe.
AB  - Relatively high 15N abundances in bone collagen of early anatomically modern
      humans in Europe have often been interpreted as a specific consumption of
      freshwater resources, even if mammoth is an alternative high 15N prey. At Buran
      Kaya III, access to associated fauna in a secured archaeological context and
      application of recently developed isotopic analyses of individuals amino acids
      offer the opportunity to further examine this hypothesis. The site of Buran-Kaya
      III is located in south Crimea and has provided a rich archaeological sequence
      including two Upper Palaeolithic layers, from which human fossils were retrieved
      and directly dated as from 37.8 to 33.1 ka cal BP. Results from bulk collagen of
      three human remains suggests the consumption of a high 15N prey besides the
      contribution of saiga, red deer, horse and hare, whose butchered remains were
      present at the site. In contrast to bulk collagen, phenylalanine and glutamic
      acid 15N abundances reflect not only animal but also plant protein contributions
      to omnivorous diet, and allow disentangling aquatic from terrestrial resource
      consumption. The inferred human trophic position values point to terrestrial
      based diet, meaning a significant contribution of mammoth meat, in addition to a
      clear intake of plant protein.

PMID- 28754956
TI  - A unique Cretaceous-Paleogene lineage of piranha-jawed pycnodont fishes.
AB  - The extinct group of the Pycnodontiformes is one of the most characteristic
      components of the Mesozoic and early Cenozoic fish faunas. These ray-finned
      fishes, which underwent an explosive morphological diversification during the
      Late Cretaceous, are generally regarded as typical shell-crushers. Here we report
      unusual cutting-type dentitions from the Paleogene of Morocco which are assigned
      to a new genus of highly specialized pycnodont fish. This peculiar taxon
      represents the last member of a new, previously undetected 40-million-year
      lineage (Serrasalmimidae fam. nov., including two other new genera and
      Polygyrodus White, 1927) ranging back to the early Late Cretaceous and leading to
      exclusively carnivorous predatory forms, unique and unexpected among pycnodonts.
      Our discovery indicates that latest Cretaceous-earliest Paleogene pycnodonts
      occupied more diverse trophic niches than previously thought, taking advantage of
      the apparition of new prey types in the changing marine ecosystems of this time
      interval. The evolutionary sequence of trophic specialization characterizing this
      new group of pycnodontiforms is strikingly similar to that observed within
      serrasalmid characiforms, from seed- and fruit-eating pacus to flesh-eating
      piranhas.

PMID- 28754957
TI  - DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c
      Myb acetylation upon matrix stiffening.
AB  - Increasing matrix stiffness caused by the extracellular matrix (ECM) deposition
      surrounding cancer cells is accompanied by epithelial-mesenchymal transition
      (EMT). Here, we show that expression levels of EMT marker genes along with
      discoidin domain receptor 2 (DDR2) can increase upon matrix stiffening. DDR2
      silencing by short hairpin RNA downregulated EMT markers. Promoter analysis and
      chromatin immunoprecipitation revealed that c-Myb and LEF1 may be responsible for
      DDR2 induction during cell culture on a stiff matrix. Mechanistically, c-Myb
      acetylation by p300, which is upregulated on the stiff matrix, seems to be
      necessary for the c-Myb-and-LEF1-mediated DDR2 expression. Finally, we found that
      the c-Myb-DDR2 axis is crucial for lung cancer cell line proliferation and
      expression of EMT marker genes in a stiff environment. Thus, our results suggest
      that DDR2 regulation by p300 expression and/or c-Myb acetylation upon matrix
      stiffening may be necessary for regulation of EMT and invasiveness of lung cancer
      cells.

PMID- 28754958
TI  - A study on the risk of fungal infection with tofacitinib (CP-690550), a novel
      oral agent for rheumatoid arthritis.
AB  - Tofacitinib (CP-690550), an oral Janus kinase inhibitor, has shown significant
      efficacy in the treatment of rheumatoid arthritis through blocking the signaling
      pathways of pro-inflammatory cytokines. However, recent evidence suggests that
      long-term tofacitinib treatment is associated with increased risk of infection
      (e.g. tuberculosis) in patients. In the present study, we illustrate that
      tofacitinib administration significantly reduced the survival rate of mice given
      lethal or sub-lethal dose challenge with Candida albicans. This was related to
      the ability of tofacitinib to reverse TNFalpha- and IFNgamma-enhanced
      candidacidal activity of murine polymorph nuclear cells (PMNs) and also to
      suppress chemokine CXCL5 expression and PMN infiltration in the infected tissues
      of mice. More importantly, tofacitinib significantly antagonized the ability of
      TNFalpha, IFNgamma and GM-CSF to boost human PMNs in phagocytosis and direct
      killing of C. albicans in vitro. It also down-regulated reactive oxygen
      production and neutrophil extracellular trap formation by human PMNs stimulated
      with yeast-derived beta-glucans in the presence of TNFalpha, IFNgamma or GM-CSF.
      Our data emphasizes a significantly increased risk for opportunistic fungal
      infection associated long-term tofacitinib treatment in humans, likely through
      antagonizing the PMN-boosting effect of pro-inflammatory cytokines.

PMID- 28754959
TI  - Investigation of simultaneously existed Raman scattering enhancement and
      inhibiting fluorescence using surface modified gold nanostars as SERS probes.
AB  - One of the main challenges for highly sensitive surface-enhanced Raman scattering
      (SERS) detection is the noise interference of fluorescence signals arising from
      the analyte molecules. Here we used three types of gold nanostars (GNSs) SERS
      probes treated by different surface modification methods to reveal the
      simultaneously existed Raman scattering enhancement and inhibiting fluorescence
      behaviors during the SERS detection process. As the distance between the metal
      nanostructures and the analyte molecules can be well controlled by these three
      surface modification methods, we demonstrated that the fluorescence signals can
      be either quenched or enhanced during the detection. We found that fluorescence
      quenching will occur when analyte molecules are closely contacted to the surface
      of GNSs, leading to a ~100 fold enhancement of the SERS sensitivity. An optimized
      Raman signal detection limit, as low as the level of 10-11 M, were achieved when
      Rhodamine 6 G were used as the analyte. The presented fluorescence-free GNSs SERS
      substrates with plentiful hot spots and controllable surface plasmon resonance
      wavelengths, fabricated using a cost-effective self-assembling method, can be
      very competitive candidates for high-sensitive SERS applications.

PMID- 28754960
TI  - A novel proton transfer mechanism in the SLC11 family of divalent metal ion
      transporters.
AB  - In humans, the H+-coupled Fe2+ transporter DMT1 (SLC11A2) is essential for proper
      maintenance of iron homeostasis. While X-ray diffraction has recently unveiled
      the structure of the bacterial homologue ScaDMT as a LeuT-fold transporter, the
      exact mechanism of H+-cotransport has remained elusive. Here, we used a
      combination of molecular dynamics simulations, in silico pK a calculations and
      site-directed mutagenesis, followed by rigorous functional analysis, to discover
      two previously uncharacterized functionally relevant residues in hDMT1 that
      contribute to H+-coupling. E193 plays a central role in proton binding, thereby
      affecting transport properties and electrogenicity, while N472 likely coordinates
      the metal ion, securing an optimally "closed" state of the protein. Our molecular
      dynamics simulations provide insight into how H+-translocation through E193 is
      allosterically linked to intracellular gating, establishing a novel transport
      mechanism distinct from that of other H+-coupled transporters.

PMID- 28754961
TI  - The Maintenance of Telomere Length in CD28+ T Cells During T Lymphocyte
      Stimulation.
AB  - Telomerase activity is not readily detected in resting human T lymphocytes,
      however upon antigen presentation, telomerase is transiently upregulated.
      Presently, it is not known if telomerase activation is necessary for the
      proliferation of T cells or for the maintenance of telomere lengths. In this
      study, we found that telomerase activation is not required for the short- term
      proliferation of T cells and that telomeres progressively shorten in a
      heterogeneous population of T cells, even if telomerase is detected. By measuring
      telomerase activity at the single-cell level using quantitative ddPCR techniques
      (ddTRAP) and by monitoring changes in the shortest telomeres with more sensitive
      telomere length measurement assays, we show that only a subset of CD28+ T-cells
      have robust telomerase activity upon stimulation and are capable of maintaining
      their telomere lengths during induced proliferation. The study of this T-cell
      subset may lead to a better understanding on how telomerase is regulated and
      functions in immune cells.

PMID- 28754962
TI  - Two dopamine D2-like receptor genes from the silkworm (Bombyx mori) and their
      evolutionary history in metazoan.
AB  - Dopamine is widely distributed in metazoans and is implicated in many
      physiological functions. Dopaminergic signaling is mediated through two classes
      of dopamine receptors, D1-like and D2-like. Phylogeny analysis reveals that, the
      dopamine receptors probably appeared ahead of the cnidarian divergence, two
      distinct classes of dopamine receptors likely formed prior to the separation of
      deuterostomes and protostomes, and INDRs probably split from its ancestor before
      the emergence of nematodes. Two D2-like genes are closely linked on the same
      scaffold, and the chromosome region around D2-like gene loci show colinearity
      among different species within Lepidoptera. These indicate two D2-like and their
      adjunction genes are likely Lepidoptera-specific orthologs, and occur by gene
      duplication event taken place after Lepidoptera ancestor split from the common
      ancestor of Lepidoptera and Diptera. In silkworm, two D2-like genes were
      expressed in examined tissues, and encoded BmDop2R2 having all the features of D2
      like receptors and BmDop2R1 being a truncated variant without the region of N
      terminal to TM II. Only dopamine distinctly lowered cAMP levels in BmDop2R2
      expressing cells, whereas all tested amines for BmDop2R1 had not markedly effect
      in pharmacological test. These suggest there is functional difference between the
      two genes, which are likely resulted from subfunctionalization of gene
      duplication.

PMID- 28754963
TI  - Transcriptome profiling of monocytes from XLA patients revealed the innate immune
      function dysregulation due to the BTK gene expression deficiency.
AB  - X-linked agammaglobulinemia (XLA) is a rare genetic disorder, caused by mutations
      in BTK (Bruton's Tyrosine Kinase) gene. Deep high-throughput RNA sequencing (RNA
      Seq) approach was utilized to explore the possible differences in transcriptome
      profiles of primary monocytes in XLA patients compared with healthy subjects. Our
      analysis revealed the differences in expression of 1,827 protein-coding genes, 95
      annotated long non-coding RNAs (lncRNAs) and 20 novel lincRNAs between XLA
      patients and healthy subjects. GO and KEGG pathway analysis of differentially
      expressed (DE) protein-coding genes showed downregulation of several innate
      immune-related genes and upregulation of oxidative phosphorylation and apoptosis
      related genes in XLA patients compared to the healthy subjects. Moreover, the
      functional prediction analysis of DE lncRNAs revealed their potential role in
      regulating the monocytes cell cycle and apoptosis in XLA patients. Our results
      suggested that BTK mutations may contribute to the dysregulation of innate immune
      system and increase susceptibility to apoptosis in monocytes of XLA patients.
      This study provides significant finding on the regulation of BTK gene in
      monocytes and the potential for development of innovative biomarkers and
      therapeutic monitoring strategies to increase the quality of life in XLA
      patients.

PMID- 28754964
TI  - Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in
      endometriosis.
AB  - EZH2, a subunit of the polycomb repressive complex 2 (PRC2) catalyzing
      trimethylation of histone H3 lysine 27 (H3K27), induces epithelial-mesenchymal
      transition (EMT) in cancers. However, whether EZH2 regulates EMT in endometriosis
      is unclear. Here, we show that EZH2 expression, along with its associated PRC2
      proteins, is significantly elevated in ectopic and eutopic endometrium from women
      with endometriosis as compared with control endometrium. EZH2 knockdown or
      inhibition restored the epithelial phenotypes of endometriotic epithelial cells,
      concomitant with the upregulation of E-cadherin and downregulation of vimentin
      and transcription factors (Snail and Slug) as well as reduced cellular migratory
      and invasive propensity. Conversely, overexpression of EZH2 induced the
      expression of Snail, Slug and vimentin and suppresses E-cadherin expression. In
      vivo administration of 3-Deazaneplanocin A (DZNep), an EZH2 inhibitor,
      significantly inhibited the growth of endometriotic lesions and improved
      generalized hyperalgesia, along with attenuated EMT and reduced fibrosis in
      endometriosis. Notably, platelets induced EZH2 upregulation and increased H3K27
      and H3K9 trimethylation levels in endometriotic epithelial cells. These data
      identify EZH2 as a novel driver of EMT in endometriosis, implicates the link
      between wound healing and epigenetic changes in the context of endometriosis, and
      underscore the role of platelets in the development of endometriosis.

PMID- 28754965
TI  - Reconstructing the historical synthesis of mauveine from Perkin and Caro:
      procedure and details.
AB  - Mauveine, an iconic dye, first synthesised in 1856 still has secrets to unveil.
      If nowadays one wanted to prepare the original Perkin's mauveine, what would be
      the procedure? It will be described in this work and lies on the use of a 1:2:1
      (mole) ratio of aniline, p-toluidine and o-toluidine. This was found from a
      comparison of a series of products synthesized from different proportions of
      these starting materials, with a set of historical samples of mauveine and
      further analysed with two unsupervised chemometrics methods.

PMID- 28754966
TI  - Rapid signal enhancement method for nanoprobe-based biosensing.
AB  - The introduction of nanomaterials as detection reagents has enabled improved
      sensitivity and facilitated detection in a variety of bioanalytical assays.
      However, high nanoprobe densities are typically needed for colorimetric detection
      and to circumvent this limitation several enhancement protocols have been
      reported. Nevertheless, there is currently a lack of universal, enzyme-free and
      versatile methods that can be readily applied to existing as well as new
      biosensing strategies. The novel method presented here is shown to enhance the
      signal of gold nanoparticles enabling visual detection of a spot containing <10
      nanoparticles. Detection of Protein G on paper arrays was improved by a 100-fold
      amplification factor in under five minutes of assay time, using IgG-labelled
      gold, silver, silica and iron oxide nanoprobes. Furthermore, we show that the
      presented protocol can be applied to a commercial allergen microarray assay,
      ImmunoCAP ISAC sIgE 112, attaining a good agreement with fluorescent detection
      when analysing human clinical samples.

PMID- 28754967
TI  - Enhanced sensing and conversion of ultrasonic Rayleigh waves by elastic
      metasurfaces.
AB  - Recent years have heralded the introduction of metasurfaces that advantageously
      combine the vision of sub-wavelength wave manipulation, with the design,
      fabrication and size advantages associated with surface excitation. An important
      topic within metasurfaces is the tailored rainbow trapping and selective spatial
      frequency separation of electromagnetic and acoustic waves using graded
      metasurfaces. This frequency dependent trapping and spatial frequency segregation
      has implications for energy concentrators and associated energy harvesting,
      sensing and wave filtering techniques. Different demonstrations of acoustic and
      electromagnetic rainbow devices have been performed, however not for deep elastic
      substrates that support both shear and compressional waves, together with surface
      Rayleigh waves; these allow not only for Rayleigh wave rainbow effects to exist
      but also for mode conversion from surface into shear waves. Here we demonstrate
      experimentally not only elastic Rayleigh wave rainbow trapping, by taking
      advantage of a stop-band for surface waves, but also selective mode conversion of
      surface Rayleigh waves to shear waves. These experiments performed at ultrasonic
      frequencies, in the range of 400-600 kHz, are complemented by time domain
      numerical simulations. The metasurfaces we design are not limited to guided
      ultrasonic waves and are a general phenomenon in elastic waves that can be
      translated across scales.

PMID- 28754968
TI  - DNA Self-assembly Catalyzed by Artificial Agents.
AB  - Nucleic acids have been shown to be versatile molecules and engineered to produce
      various nanostructures. However, the poor rate of these uncatalyzed nucleic acid
      reactions has restricted the development and applications. Herein, we reported a
      novel finding that DNA self-assembly could be nonenzymatically catalyzed by
      artificial agents with an increasing dissociation rate constant K2. The catalytic
      role of several artificial agents in DNA self-assembly was verified by real-time
      fluorescent detection or agarose gel electrophoresis. We found that 20% PEG 200
      could significantly catalyze DNA self-assembly and increase the reaction
      efficiency, such as linear hybridization chain reaction (HCR) and exponential
      hairpin assembly (EHA). Therefore, we foresee that a fast and efficient DNA self
      assembly in structural DNA nanotechnology will be desirable.

PMID- 28754969
TI  - Enhanced treatment of dispersed dye-production wastewater by self-assembled
      organobentonite in a one-step process with poly-aluminium chloride.
AB  - Organobentonite has been successfully applied in industrial wastewater treatment.
      However, the solid-liquid separation in wastewater treatment still needs
      improvement. This study presents an enhanced approach with high removal
      efficiency and short separation time for dispersed dye-production wastewater
      using self-assembled organobentonite in a one-step process with poly-aluminium
      chloride (PAC). The enhanced effects of PAC on wastewater treatment by
      organobentonite were comprehensively evaluated. Following the primary
      decontamination by the self-assembled organobentonite, the removal efficiency for
      dispersed dye-production wastewater was strengthened with PAC coagulation. The
      removal rates of TOC and organic pollutants were 55.0% and 63.5%, respectively,
      with the PAC-enhanced approach and were 1.3- and 1.6-fold higher, respectively,
      than those with the self-assembled organobentonite approach. The combination of
      PAC with self-assembled organobentonite was able to break the stability of the
      organobentonite suspension and enlarge the floc size, and thus reduce the solid
      liquid separation time from 30 min to 10 min. Additionally, this enhanced
      approach could improve the biodegradability of wastewater with the BOD5/CODCr
      ratio increasing from 0.22 to 0.39, which was 4.1-fold higher than that of only
      organobentonite in a one-step process. Therefore, the PAC-enhanced approach could
      be a promising technology for wastewater pretreatment in practical industrial
      applications.

PMID- 28754970
TI  - Dissimilatory Nitrate Reduction to Ammonium in the Yellow River Estuary: Rates,
      Abundance, and Community Diversity.
AB  - Dissimilatory nitrate reduction to ammonium (DNRA) is an important nitrate
      reduction process in estuarine sediments. This study reports the first
      investigation of DNRA in the Yellow River Estuary located in Eastern Shandong,
      China. Saltwater intrusion could affect the physicochemical characteristics and
      change the microbial community structure of sediments. In this study, the
      activity, abundance and community diversity of DNRA bacteria were investigated
      during saltwater intrusion. The slurry incubation experiments combined with
      isotope-tracing techniques and qPCR results showed that DNRA rates and nrfA (the
      functional gene of DNRA bacteria) gene abundance varied over wide ranges across
      different sites. DNRA rates had a positive and significant correlation with
      sediment organic content and extractable NH4+, while DNRA rates were weakly
      correlated with nrfA gene abundance. In comparison, the activities and abundance
      of DNRA bacteria did not change with a trend along salinity gradient.
      Pyrosequencing analysis of nrfA gene indicated that delta-proteobacteria was the
      most abundant at all sites, while epsilon-proteobacteria was hardly found. This
      study reveals that variability in the activities and community structure of DNRA
      bacteria is largely driven by changes in environmental factors and provides new
      insights into the characteristics of DNRA communities in estuarine ecosystems.

PMID- 28754971
TI  - In vivo Raman spectral analysis of impaired cervical remodeling in a mouse model
      of delayed parturition.
AB  - Monitoring cervical structure and composition during pregnancy has high potential
      for prediction of preterm birth (PTB), a problem affecting 15 million newborns
      annually. We use in vivo Raman spectroscopy, a label-free, light-based method
      that provides a molecular fingerprint to non-invasively investigate normal and
      impaired cervical remodeling. Prostaglandins stimulate uterine contractions and
      are clinically used for cervical ripening during pregnancy. Deletion of
      cyclooxygenase-1 (Cox-1), an enzyme involved in production of these
      prostaglandins, results in delayed parturition in mice. Contrary to expectation,
      Cox-1 null mice displayed normal uterine contractility; therefore, this study
      sought to determine whether cervical changes could explain the parturition
      differences in Cox-1 null mice and gestation-matched wild type (WT) controls.
      Raman spectral changes related to extracellular matrix proteins, lipids, and
      nucleic acids were tracked over pregnancy and found to be significantly delayed
      in Cox-1 null mice at term. A cervical basis for the parturition delay was
      confirmed by other ex vivo tests including decreased tissue distensibility,
      hydration, and elevated progesterone levels in the Cox-1 null mice at term. In
      conclusion, in vivo Raman spectroscopy non-invasively detected abnormal
      remodeling in the Cox-1 null mouse, and clearly demonstrated that the cervix
      plays a key role in their delayed parturition.

PMID- 28754972
TI  - The Association of Ambient Temperature and Violent Crime.
AB  - It is controversial if global warming will result into increased crime and
      conflict rate, and no causal neurobiological mechanisms have been proposed for
      the putative association between ambient temperature and aggressive behavior.
      This study shows that during 1996-2013, ambient temperature explained 10% of
      variance in the violent crime rate in Finland, corresponding to a 1.7%
      increase/degree centigrade. Ambient temperature also correlated with a one month
      delay in circannual changes in peripheral serotonin transporter density among
      both offenders and healthy control subjects, which itself correlated strongly
      with the monthly violent crime rate. This suggests that rise in temperature
      modulates serotonergic transmission which may increase impulsivity and general
      human activity level, resulting into increase in social interaction and risk of
      violent incidents. Together, these results suggest that the effect of ambient
      temperature on occurrence of violent crime is partly mediated through the
      serotonergic system, and that a 2  degrees C increase in average temperatures
      would increase violent crime rates by more than 3% in non-tropical and non
      subtropical areas, if other contributing factors remained constant.

PMID- 28754973
TI  - Neuroprotective Effects of Trigeminal Nerve Stimulation in Severe Traumatic Brain
      Injury.
AB  - Following traumatic brain injury (TBI), ischemia and hypoxia play a major role in
      further worsening of the damage, a process referred to as 'secondary injury'.
      Protecting neurons from causative factors of secondary injury has been the
      guiding principle of modern TBI management. Stimulation of trigeminal nerve
      induces pressor response and improves cerebral blood flow (CBF) by activating the
      rostral ventrolateral medulla. Moreover, it causes cerebrovasodilation through
      the trigemino-cerebrovascular system and trigemino-parasympathetic reflex. These
      effects are capable of increasing cerebral perfusion, making trigeminal nerve
      stimulation (TNS) a promising strategy for TBI management. Here, we investigated
      the use of electrical TNS for improving CBF and brain oxygen tension (PbrO2),
      with the goal of decreasing secondary injury. Severe TBI was produced using
      controlled cortical impact (CCI) in a rat model, and TNS treatment was delivered
      for the first hour after CCI. In comparison to TBI group, TBI animals with TNS
      treatment demonstrated significantly increased systemic blood pressure, CBF and
      PbrO2 at the hyperacute phase of TBI. Furthermore, rats in TNS-treatment group
      showed significantly reduced brain edema, blood-brain barrier disruption, lesion
      volume, and brain cortical levels of TNF-alpha and IL-6. These data provide
      strong early evidence that TNS could be an effective neuroprotective strategy.

PMID- 28754974
TI  - Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier
      dysfunction in experimental acute pancreatitis.
AB  - The release of inflammatory cytokines, that plays a dominant role in local
      pancreatic inflammation and systemic complications in severe acute pancreatitis
      (SAP). High-mobility group box 1 (HMGB1) is implicated in the mechanism of organ
      dysfunction and bacterial translocation in SAP. This current study aims to
      investigate possible role of HMGB1 in the intestinal mucosal barrier dysfunction
      of SAP, and the effect of anti-HMGB1 antibody treatment in intestinal mucosal
      injury in SAP. Our data revealed that the HMGB1 expression was significantly
      increased in AP mice induced by caerulein and LPS, and the inhibition of HMGB1
      played a protective role in intestinal mucosal barrier dysfunction, reduced the
      serum level of other proinflammatory cytokines include IL-1beta, IL-6, TNF-alpha.
      Next we investigated the downstream receptors involving in HMGB1 signaling. We
      found that the expressions of toll-like receptor (TLR) 4 and TLR9 were elevated
      in ileum of AP mice, the administration of HMGB1 neutralizing antibody
      significantly reduced the TLR4 and TLR9 expression. It was concluded that HMGB1
      contributed the mechanism to the intestinal mucosal barrier dysfunction during
      AP. Blockade of HMGB1 by administration of HMGB1 neutralizing antibody may be a
      beneficial therapeutic strategy in improving intestinal mucosal barrier
      dysfunction in SAP.

PMID- 28754975
TI  - Bandwidth broadening of a linear polarization converter by near-field metasurface
      coupling.
AB  - We experimentally demonstrate a highly efficient, broadband linear polarization
      converter functioning at terahertz frequencies. The linear polarization converter
      is composed of three metasurfaces and two dielectric layers interlaced with each
      other. The neighboring unit cells of the central metasurface layer of the linear
      polarization converter exhibit strong electromagnetic coupling, which increases
      the number of resonances and results in significant bandwidth broadening. The
      simulation and experimental results show that in the frequency range of 0.2 to
      0.4 THz, the proposed polarization converter has a flat transmission curve and
      exhibits a transmission efficiency that is higher than 80%. High performance
      terahertz polarization conversion is desirable in many fields, such as terahertz
      spectroscopy, imaging, and communications.

PMID- 28754976
TI  - Constraining shifts in North Atlantic plate motions during the Palaeocene by U-Pb
      dating of Svalbard tephra layers.
AB  - Radioisotopic dating of volcanic minerals is a powerful method for establishing
      absolute time constraints in sedimentary basins, which improves our understanding
      of the chronostratigraphy and evolution of basin processes. The relative plate
      motions of Greenland, North America, and Eurasia changed several times during the
      Palaeogene. However, the timing of a key part of this sequence, namely the
      initiation of compression between Greenland and Svalbard, is currently poorly
      constrained. The formation of the Central Basin in Spitsbergen is inherently
      linked to changes in regional plate motions, so an improved chronostratigraphy of
      the sedimentary sequence is warranted. Here we present U-Pb zircon dates from
      tephra layers close to the basal unconformity, which yield a weighted-mean
      206Pb/238U age of 61.596 +/- 0.028 Ma (2sigma). We calculate that sustained
      sedimentation began at ~61.8 Ma in the eastern Central Basin based on a sediment
      accumulation rate of 71.6 +/- 7.6 m/Myr. The timing of basin formation is broadly
      coeval with depositional changes at the Danian-Selandian boundary around the
      other margins of Greenland, including the North Sea, implying a common tectonic
      driving force. Furthermore, these stratigraphic tie points place age constraints
      on regional plate reorganization events, such as the onset of seafloor spreading
      in the Labrador Sea.

PMID- 28754977
TI  - Metabolic syndrome is associated with an increased incidence of subclinical
      hypothyroidism - A Cohort Study.
AB  - Prior cross-sectional analyses have demonstrated an association between
      subclinical hypothyroidism and metabolic syndrome and selected components.
      However, the temporal relation between metabolic syndrome and declining thyroid
      function remains unclear. In a prospective study, an unselected cohort of 66,822
      participants with and without metabolic syndrome were followed. A proportional
      hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs for
      hypothyroidism. Exploratory analyses for the relation between components of
      metabolic syndrome and declining thyroid function were also undertaken. During an
      average follow-up of 4.2 years, the incident rates for subclinical hypothyroidism
      were substantially higher in participants who began the study with metabolic
      syndrome compared with metabolically normal controls. After controlling for risk
      factors, patients with metabolic syndrome were at a 21% excess risk of developing
      subclinical hypothyroidism (adjusted HR 1.21; 95% CI 1.03-1.42). When individual
      components were analyzed, an increased risk of subclinical hypothyroidism was
      associated with high blood pressure (1.24; 1.04-1.48) and high serum
      triglycerides (1.18; 1.00-1.39), with a trend of increasing risk as participants
      had additional more components. Individuals with metabolic syndrome are at a
      greater risk for developing subclinical hypothyroidism, while its mechanisms and
      temporal consequences of this observation remain to be determined.

PMID- 28754978
TI  - Integrated diagnostic network construction reveals a 4-gene panel and 5 cancer
      hallmarks driving breast cancer heterogeneity.
AB  - Breast cancer encompasses a group of heterogeneous diseases, each associated with
      distinct clinical implications. Dozens of molecular biomarkers capable of
      categorizing tumors into clinically relevant subgroups have been proposed which,
      though considerably contribute in precision medicine, complicate our
      understandings toward breast cancer subtyping and its clinical translation. To
      decipher the networking of markers with diagnostic roles on breast carcinomas, we
      constructed the diagnostic networks by incorporating 6 publically available gene
      expression datasets with protein interaction data retrieved from BioGRID on
      previously identified 1015 genes with breast cancer subtyping roles. The Greedy
      algorithm and mutual information were used to construct the integrated diagnostic
      network, resulting in 37 genes enclosing 43 interactions. Four genes, FAM134B,
      KIF2C, ALCAM, KIF1A, were identified having comparable subtyping efficacies with
      the initial 1015 genes evaluated by hierarchical clustering and cross validations
      that deploy support vector machine and k nearest neighbor algorithms. Pathway,
      Gene Ontology, and proliferation marker enrichment analyses collectively suggest
      5 primary cancer hallmarks driving breast cancer differentiation, with those
      contributing to uncontrolled proliferation being the most prominent. Our results
      propose a 37-gene integrated diagnostic network implicating 5 cancer hallmarks
      that drives breast cancer heterogeneity and, in particular, a 4-gene panel with
      clinical diagnostic translation potential.

PMID- 28754979
TI  - Thresholds of biodiversity and ecosystem function in a forest ecosystem
      undergoing dieback.
AB  - Ecological thresholds, which represent points of rapid change in ecological
      properties, are of major scientific and societal concern. However, very little
      research has focused on empirically testing the occurrence of thresholds in
      temperate terrestrial ecosystems. To address this knowledge gap, we tested
      whether a number of biodiversity, ecosystem functions and ecosystem condition
      metrics exhibited thresholds in response to a gradient of forest dieback,
      measured as changes in basal area of living trees relative to areas that lacked
      recent dieback. The gradient of dieback was sampled using 12 replicate study
      areas in a temperate forest ecosystem. Our results provide novel evidence of
      several thresholds in biodiversity (namely species richness of ectomycorrhizal
      fungi, epiphytic lichen and ground flora); for ecological condition (e.g. sward
      height, palatable seedling abundance) and a single threshold for ecosystem
      function (i.e. soil respiration rate). Mechanisms for these thresholds are
      explored. As climate-induced forest dieback is increasing worldwide, both in
      scale and speed, these results imply that threshold responses may become
      increasingly widespread.

PMID- 28754980
TI  - Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second
      Heart Field during Outflow Tract Development.
AB  - The cardiac neural crest cells (cNCCs) and the second heart field (SHF) play key
      roles in development of the cardiac outflow tract (OFT) for establishment of
      completely separated pulmonary and systemic circulations in vertebrates. A
      neurovascular guiding factor, Semaphorin 3c (Sema3c), is required for the
      development of the OFT, however, its regulation of the interaction between cNCCs
      and SHF remains to be determined. Here, we show that a Sema3c is a candidate that
      mediates interaction between cNCCs and the SHF during development of the OFT.
      Foxc1/c2 directly activates the transcription of Sema3c in the OFT, whereas, a
      hypomorph of Tbx1, a key SHF transcription factor, resulted in the ectopic
      expression of Sema3c in the pharyngeal arch region. Fgf8, a downstream secreted
      factor of Tbx1, inhibited the expression of Sema3c in cNCCs via activation of
      ERK1/2 signaling. Blocking of FGF8 caused ectopic expression of SEMA3C and a
      migration defect of cNCCs, resulting in abnormal chick pharyngeal arch
      development. These results suggest that proper spatio-temporal expression of
      Sema3c, regulated positively by Foxc1/c2 and negatively by the Tbx1-Fgf8 cascade,
      respectively, is essential for the interaction between cNCCs and the SHF that
      correctly navigates cNCCs towards the OFT, composed of SHF-derived cells.

PMID- 28754981
TI  - Cyclin-dependent kinase 9 is required for the survival of adult Drosophila
      melanogaster glia.
AB  - Neuronal and glial progenitor cells exist in the adult Drosophila brain. The
      primarily glial progenitor cells rely on a microRNA, mir-31a, to inhibit the
      expression of a predicted E3 ubiquitin ligase, CG16947. Erroneous inheritance of
      CG16947 by the progeny when the neural progenitor cell divides leads to death of
      the progeny, however how CG16947 achieves glial cell death is unknown. I have
      identified the interacting partner of CG16947 to be cdk9. I show that reduction
      of cdk9 expression in glia causes glial loss; highlighting the importance of cdk9
      in mediating the survival of glia. Further, glial loss observed in mir-31a
      mutants was prevented with adult-specific expression of cdk9 in glia. I provide
      biochemical evidence that the binding of CG16947 to cdk9 causes its degradation.
      Taken together, this data shows that cdk9 plays a role in the survival of adult
      glia in the Drosophila brain. Thus, a fine balance exists between mir-31a and
      CG16947 expression in the progenitor cells that in turn regulates the levels of
      cdk9 in the progeny. This serves to allow the progenitor cells to regulate the
      number of glia in the adult brain.

PMID- 28754982
TI  - Recombinant attenuated Salmonella Typhimurium with heterologous expression of the
      Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection.
AB  - Non-typhoidal Salmonella are associated with gastrointestinal disease worldwide
      and invasive disease in Africa. We constructed novel bivalent vaccines through
      the recombinant expression of heterologous O-antigens from Salmonella
      Choleraesuis in Salmonella Typhimurium. A recombinant Asd+ plasmid pCZ1 with the
      cloned Salmonella Choleraesuis O-antigen gene cluster was introduced into three
      constructed Salmonella Typhimurium Deltaasd mutants: SLT11 (DeltarfbP), SLT12
      (DeltarmlB-rfbP) and SLT16 (DeltarfbP ?pagL::TT araCPBAD rfbP). Immunoblotting
      demonstrated that SLT11 (pCZ1) and SLT12 (pCZ1) efficiently expressed the
      heterologous O-antigen. In the presence of arabinose, SLT16 (pCZ1) expressed both
      the homologous and heterologous O-antigens, whereas in the absence of arabinose,
      SLT16 (pCZ1) mainly expressed the heterologous O-antigen. We deleted the crp/cya
      genes in SLT12 (pCZ1) and SLT16 (pCZ1) for attenuation purposes, generating the
      recombinant vaccine strains SLT17 (pCZ1) and SLT18 (pCZ1). Immunization with
      either SLT17 (pCZ1) or SLT18 (pCZ1) induced specific IgG against the heterologous
      O-antigen, which mediated significant killing of Salmonella Choleraesuis and
      provided full protection against a lethal homologous challenge in mice.
      Furthermore, SLT17 (pCZ1) or SLT18 (pCZ1) immunization resulted in 83% or 50%
      heterologous protection against Salmonella Choleraesuis challenge, respectively.
      Our study demonstrates that heterologous O-antigen expression is a promising
      strategy for the development of multivalent Salmonella vaccines.

PMID- 28754983
TI  - Urinary concentrations of phthalate metabolites in early pregnancy associated
      with clinical pregnancy loss in Chinese women.
AB  - Limited evidence revealed conflicting results on relationship between phthalate
      exposure and clinical pregnancy loss (gestational weeks >6). A prospective cohort
      study in Chinese pregnant women (n = 3220) was conducted to investigate the
      association between urinary phthalate metabolites and clinical pregnancy loss
      (gestational weeks 6 to 27; n = 109). Morning urine samples during gestational
      weeks 5 to 14 (mean 10.42) were collected to measure monomethyl phthalate (MMP),
      monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate
      (MBzP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate
      (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). The concentrations
      of low- and high-molecular weight phthalate metabolites (SigmaLMWP <250 Da and
      SigmaHMWP >250 Da) were calculated. Adjusted logistic regression models showed
      increased risks of clinical pregnancy loss in women with higher creatinine-
      normalized concentrations of MEP, MBP, MEOHP, MEHHP, SigmaLMWP and SigmaHMWP.
      Stratified analysis by gestational weeks (10 weeks) of miscarriage indicated
      positive associations of MEP, MEOHP, MEHHP and SigmaHMWP with embryonic loss
      (during gestational weeks 6 to 10). The only association of foetal loss (during
      gestational weeks 11 to 27) was observed with MEHHP. Our findings suggested that
      Chinese women who were exposed to phthalates during early pregnancy had an
      increased risk of clinical pregnancy loss, especially embryonic loss.

PMID- 28754984
TI  - The interfacial pH of acidic degradable polymeric biomaterials and its effects on
      osteoblast behavior.
AB  - A weak alkaline environment is established to facilitate the growth of
      osteoblasts. Unfortunately, this is inconsistent with the application of
      biodegradable polymer in bone regeneration, as the degradation products are
      usually acidic. In this study, the variation of the interfacial pH of poly (D, L
      lactide) and piperazine-based polyurethane ureas (P-PUUs), as the representations
      of acidic degradable materials, and the behavior of osteoblasts on these
      substrates with tunable interfacial pH were investigated in vitro. These results
      revealed that the release of degraded products caused a rapid decrease in the
      interfacial pH, and this could be relieved by the introduction of alkaline
      segments. On the contrary, when culturing with osteoblasts, the variation of the
      interfacial pH revealed an upward tendency, indicating that cell could construct
      the microenvironment by secreting cellular metabolites to satisfy its own
      survival. In addition, the behavior of osteoblasts on substrates exhibited that P
      PUUs with the most PP units were better for cell growth and osteogenic
      differentiation of cells. This is due to the hydrophilic surface and the moderate
      N% in P-PUUs, key factors in the promotion of the early stages of cellular
      responses, and the interfacial pH contributing to the enhanced effect on
      osteogenic differentiation.

PMID- 28754985
TI  - Epigenetic changes in myelofibrosis: Distinct methylation changes in the myeloid
      compartments and in cases with ASXL1 mutations.
AB  - This is the first study to compare genome-wide DNA methylation profiles of sorted
      blood cells from myelofibrosis (MF) patients and healthy controls. We found that
      differentially methylated CpG sites located to genes involved in 'cancer' and
      'embryonic development' in MF CD34+ cells, in 'inflammatory disease' in MF
      mononuclear cells, and in 'immunological diseases' in MF granulocytes. Only few
      differentially methylated CpG sites were common among the three cell populations.
      Mutations in the epigenetic regulators ASXL1 (47%) and TET2 (20%) were not
      associated with a specific DNA methylation pattern using an unsupervised
      approach. However, in a supervised analysis of ASXL1 mutated versus wild-type
      cases, differentially methylated CpG sites were enriched in regions marked by
      histone H3K4me1, histone H3K27me3, and the bivalent histone mark H3K27me3 +
      H3K4me3 in human CD34+ cells. Hypermethylation of selected CpG sites was
      confirmed in a separate validation cohort of 30 MF patients by pyrosequencing.
      Altogether, we show that individual MF cell populations have distinct
      differentially methylated genes relative to their normal counterparts, which
      likely contribute to the phenotypic characteristics of MF. Furthermore,
      differentially methylated CpG sites in ASXL1 mutated MF cases are found in
      regulatory regions that could be associated with aberrant gene expression of
      ASXL1 target genes.

PMID- 28754986
TI  - Direct estimation of the global distribution of vertical velocity within cirrus
      clouds.
AB  - Cirrus clouds determine the radiative balance of the upper troposphere and the
      transport of water vapor across the tropopause. The representation of vertical
      wind velocity, W, in atmospheric models constitutes the largest source of
      uncertainty in the calculation of the cirrus formation rate. Using global
      atmospheric simulations with a spatial resolution of 7 km we obtain for the first
      time a direct estimate of the distribution of W at the scale relevant for cirrus
      formation, validated against long-term observations at two different ground
      sites. The standard deviation in W, sigma w , varies widely over the globe with
      the highest values resulting from orographic uplift and convection, and the
      lowest occurring in the Arctic. Globally about 90% of the simulated sigma w
      values are below 0.1 m s-1 and about one in 104 cloud formation events occur in
      environments with sigma w  > 0.8 m s-1. Combining our estimate with reanalysis
      products and an advanced cloud formation scheme results in lower homogeneous ice
      nucleation frequency than previously reported, and a decreasing average ice
      crystal concentration with decreasing temperature. These features are in
      agreement with observations and suggest that the correct parameterization of
      sigma w is critical to simulate realistic cirrus properties.

PMID- 28754987
TI  - Influence of aridity and salinity on plant nutrients scales up from species to
      community level in a desert ecosystem.
AB  - Soil moisture and salt play key roles in regulating desert plant nutrient cycles
      on a local scale. However, information on the response of plant nutrient
      stoichiometric patterns to soil water and salt gradients is limited. Here, we
      assessed leaf N and P levels of 18 species of desert plants and measured the
      corresponding soil nutrient, water and salt concentrations, at four dry sites,
      five humid-saline sites and four humid-non-saline sites (reference sites) along a
      transect in a temperate desert in Xinjiang Province, northwest China. Our results
      indicated that the desert plants had lower N and P concentrations and higher N:P
      mass ratios in dry and humid-saline sites than in the humid-non-saline sites.
      Unlike the single-factor effect of salinity driving the plasticity of species N
      concentration, aridity and salinity interacted in their impact on the plasticity
      of plant P and the N:P ratio. Moreover, the plant community N and P
      concentrations and N:P ratio exhibited significant positive linear and nonlinear
      correlations with soil moisture in shallow and deep soil, respectively. Aridity
      reduced the N plasticity and increased P plasticity of the plant community. The
      results strongly supported the hypothesis that soil moisture and salt
      concentration were the dominant drivers of leaf N and P concentrations and their
      plasticity across species and community scales.

PMID- 28754988
TI  - Zinc binding to RNA recognition motif of TDP-43 induces the formation of amyloid
      like aggregates.
AB  - Aggregation of TDP-43 (transactive response DNA binding protein 43 kDa) is a
      hallmark of certain forms of amyotrophic lateral sclerosis (ALS) and
      frontotemporal lobar degeneration (FTLD). Moreover, intracellular TDP-43-positive
      inclusions are often found in other neurodegenerative diseases. Recently it was
      shown that zinc ions can provoke the aggregation of endogenous TDP-43 in cells,
      allowing to assume a direct interaction of TDP-43 with zinc ions. In this work,
      we investigated zinc binding to the 102-269 TDP-43 fragment, which comprise the
      two RNA recognition motifs. Using isothermal titration calorimetry, mass
      spectrometry, and differential scanning fluorimetry, we showed that zinc binds to
      this TDP-43 domain with a dissociation constant in the micromolar range and
      modifies its tertiary structure leading to a decrease of its thermostability.
      Moreover, the study by dynamic light scattering and negative stain electron
      microscopy demonstrated that zinc ions induce auto-association process of this
      TDP-43 fragment into rope-like structures. These structures are thioflavin-T
      positive allowing to hypothesize the direct implication of zinc ions in
      pathological aggregation of TDP-43.

PMID- 28754989
TI  - Efficiency of ddRAD target enriched sequencing across spiny rock lobster species
      (Palinuridae: Jasus).
AB  - Double digest restriction site-associated DNA sequencing (ddRADseq) and target
      capture sequencing methods are used to explore population and phylogenetic
      questions in non-model organisms. ddRADseq offers a simple and reliable protocol
      for population genomic studies, however it can result in a large amount of
      missing data due to allelic dropout. Target capture sequencing offers an
      opportunity to increase sequencing coverage with little missing data and
      consistent orthologous loci across samples, although this approach has generally
      been applied to conserved markers for deeper evolutionary questions. Here, we
      combine both methods to generate high quality sequencing data for population
      genomic studies of all marine lobster species from the genus Jasus. We designed
      probes based on ddRADseq libraries of two lobster species (Jasus edwardsii and
      Sagmariasus verreauxi) and evaluated the captured sequencing data in five other
      Jasus species. We validated 4,465 polymorphic loci amongst these species using a
      cost effective sequencing protocol, of which 1,730 were recovered from all
      species, and 4,026 were present in at least three species. The method was also
      successfully applied to DNA samples obtained from museum specimens. This data
      will be further used to assess spatial-temporal genetic variation in Jasus
      species found in the Southern Hemisphere.

PMID- 28754990
TI  - Assessments of iodoindoles and abamectin as inducers of methuosis in pinewood
      nematode, Bursaphelenchus xylophilus.
AB  - Bursaphelenchus xylophilus is a quarantined migratory endoparasite known to cause
      severe economic losses in pine forest ecosystems. The study presents the
      nematicidal effects of halogenated indoles on B. xylophilus and their action
      mechanisms. 5-Iodoindole and abamectin (positive control) at low concentration
      (10 ug/mL) presented similar and high nematicidal activities against B.
      xylophilus. 5-Iodoindole diminished fecundity, reproductive activities, embryonic
      and juvenile lethality and locomotor behaviors. Molecular interactions of ligands
      with invertebrate-specific glutamate gated chloride channel receptor reinforced
      the notion that 5-iodoindole, like abamectin, rigidly binds to the active sites
      of the receptor. 5-Iodoindole also induced diverse phenotypic deformities in
      nematodes including abnormal organ disruption/shrinkage and increased
      vacuolization. These findings suggest the prospective role of vacuoles in
      nematode death by methuosis. Importantly, 5-iodoindole was nontoxic to two
      plants, Brassica oleracea and Raphanus raphanistrum. Henceforth, the study
      warrants the application of iodoindoles in ecological environments to control the
      devastating pine destruction by B. xylophilus.

PMID- 28754991
TI  - PyroTyping, a novel pyrosequencing-based assay for Mycobacterium tuberculosis
      genotyping.
AB  - We developed a novel method, PyroTyping, for discrimination of Mycobacterium
      tuberculosis isolates combining pyrosequencing and IS6110 polymorphism. A total
      of 100 isolates were analysed with IS6110-restriction fragment length
      polymorphism (RFLP), spoligotyping, mycobacterial interspersed repetitive units -
      variable number tandem repeats (MIRU-VNTR), and PyroTyping. PyroTyping results
      regarding clustering or discrimination of the isolates were highly concordant
      with the other typing methods performed. PyroTyping is more rapid than RFLP and
      presents the same discriminatory power, thus, it may be useful for taking timely
      decisions for tuberculosis control.

PMID- 28754992
TI  - Observed crowding effects on Mycobacterium tuberculosis 2-trans-enoyl-ACP (CoA)
      reductase enzyme activity are not due to excluded volume only.
AB  - The cellular milieu is a complex and crowded aqueous solution. Macromolecular
      crowding effects are commonly studied in vitro using crowding agents. The aim of
      the present study was to evaluate the effects, if any, of macromolecular
      synthetic crowding agents on the apparent steady-state kinetic parameters (K m ,
      k cat , and k cat /K m ) of Mycobacterium tuberculosis 2-trans-enoyl-ACP (CoA)
      reductase (InhA). Negligible effects on InhA activity were observed for ficoll
      70, ficoll 400 and dextran 70. A complex effect was observed for PEG 6000.
      Glucose and sucrose showed, respectively, no effect on InhA activity and
      decreased k cat /K m for NADH and k cat for 2-trans-dodecenoyl-CoA. Molecular
      dynamics results suggest that InhA adopts a more compact conformer in sucrose
      solution. The effects of the crowding agents on the energy (E a and E eta ),
      enthalpy (?H # ), entropy (?S # ), and Gibbs free energy (?G # ) of activation
      were determined. The ?G # values for all crowding agents were similar to buffer,
      suggesting that excluded volume effects did not facilitate stable activated ES #
      complex formation. Nonlinear Arrhenius plot for PEG 6000 suggests that "soft"
      interactions play a role in crowding effects. The results on InhA do not
      unequivocally meet the criteria for crowding effect due to exclude volume only.

PMID- 28754993
TI  - Neurometabolic and electrophysiological changes during cortical spreading
      depolarization: multimodal approach based on a lactate-glucose dual
      microbiosensor arrays.
AB  - Spreading depolarization (SD) is a slow propagating wave of strong depolarization
      of neural cells, implicated in several neuropathological conditions. The
      breakdown of brain homeostasis promotes significant hemodynamic and metabolic
      alterations, which impacts on neuronal function. In this work we aimed to develop
      an innovative multimodal approach, encompassing metabolic, electric and
      hemodynamic measurements, tailored but not limited to study SD. This was based on
      a novel dual-biosensor based on microelectrode arrays designed to simultaneously
      monitor lactate and glucose fluctuations and ongoing neuronal activity with high
      spatial and temporal resolution. In vitro evaluation of dual lactate-glucose
      microbiosensor revealed an extended linear range, high sensitivity and
      selectivity, fast response time and low oxygen-, temperature- and pH-
      dependencies. In anesthetized rats, we measured with the same array a significant
      drop in glucose concentration matched to a rise in lactate and concurrently with
      pronounced changes in the spectral profile of LFP-related currents during
      episodes of mechanically-evoked SD. This occurred along with the stereotypical
      hemodynamic response of the SD wave. Overall, this multimodal approach
      successfully demonstrates the capability to monitor metabolic alterations and
      ongoing electrical activity, thus contributing to a better understanding of the
      metabolic changes occurring in the brain following SD.

PMID- 28754994
TI  - 1H NMR-based Investigation of Metabolic Response to Electro-Acupuncture
      Stimulation.
AB  - Acupuncture is a traditional Chinese medicine therapy that has been found useful
      for treating various diseases. The treatments involve the insertion of fine
      needles at acupoints along specific meridians (meridian specificity). This study
      aims to investigate the metabolic basis of meridian specificity using proton
      nuclear magnetic resonance (1H NMR)-based metabolomics. Electro-acupuncture (EA)
      stimulations were performed at acupoints of either Stomach Meridian of Foot
      Yangming (SMFY) or Gallbladder Meridian of Foot-Shaoyang (GMFS) in healthy male
      Sprague Dawley (SD) rats. 1H-NMR spectra datasets of serum, urine, cortex, and
      stomach tissue extracts from the rats were analysed by multivariate statistical
      analysis to investigate metabolic perturbations due to EA treatments at different
      meridians. EA treatment on either the SMFY or GMFS acupoints induced significant
      variations in 31 metabolites, e.g., amino acids, organic acids, choline esters
      and glucose. Moreover, a few meridian-specific metabolic changes were found for
      EA stimulations on the SMFY or GMFS acupoints. Our study demonstrated significant
      metabolic differences in response to EA stimulations on acupoints of SMFY and
      GMFS meridians. These results validate the hypothesis that meridian specificity
      in acupuncture is detectable in the metabolome and demonstrate the feasibility
      and effectiveness of a metabolomics approach in understanding the mechanism of
      acupuncture.

PMID- 28754995
TI  - Genetic variation and population structure of Botswana populations as identified
      with AmpFLSTR Identifiler short tandem repeat (STR) loci.
AB  - Population structure was investigated in 990 Botswana individuals according to
      ethno-linguistics, Bantu and Khoisan, and geography (the nine administrative
      districts) using the Identifiler autosomal microsatellite markers. Genetic
      diversity and forensic parameters were calculated for the overall population, and
      according to ethno-linguistics and geography. The overall combined power of
      exclusion (CPE) was 0.9999965412 and the combined match probability 6,28 * 10-19.
      CPE was highest for the Khoisan Tuu ethnolinguistic group and the Northeast
      District at 0.9999582029 and 0.9999922652 respectively. CMP ranged from 6.28 * 10
      19 (Khoisan Tuu) to 1,02 * 10-18 (Northwest district). Using pairwise genetic
      distances (FST), analysis of molecular variance (AMOVA), factorial correspondence
      analysis (FCA), and the unsupervised Bayesian clustering method found in
      STRUCTURE and TESS, ethno-linguistics were found to have a greater influence on
      population structure than geography. FCA showed clustering between Bantu and
      Khoisan, and within the Bantu. This Bantu sub-structuring was not seen with
      STRUCTURE and TESS, which detected clustering only between Bantu and Khoisan. The
      patterns of population structure revealed highlight the need for regional
      reference databases that include ethno-linguistic and geographic location
      information. These markers have important potential for bio-anthropological
      studies as well as for forensic applications.

PMID- 28754996
TI  - Image-Based Chemical Structure Determination.
AB  - Chemical imaging is a powerful tool for understanding the chemical composition
      and nature of heterogeneous samples. Recent developments in elemental,
      vibrational, and mass-spectrometric chemical imaging with high spatial resolution
      (50-200 nm) and reasonable timescale (a few hours) are capable of providing
      complementary chemical information about various samples. However, a single
      technique is insufficient to provide a comprehensive understanding of chemically
      complex materials. For bulk samples, the combination of different analytical
      methods and the application of statistical methods for extracting correlated
      information across different techniques is a well-established and powerful
      concept. However, combined multivariate analytics of chemical images obtained via
      different imaging techniques is still in its infancy, hampered by a lack of
      analytical methodologies for data fusion and analysis. This study demonstrates
      the application of multivariate statistics to chemical images taken from the same
      sample via various methods to assist in chemical structure determination.

PMID- 28754997
TI  - Dual-Function Au@Y2O3:Eu3+ Smart Film for Enhanced Power Conversion Efficiency
      and Long-Term Stability of Perovskite Solar Cells.
AB  - In the present study, a dual-functional smart film combining the effects of
      wavelength conversion and amplification of the converted wave by the localized
      surface plasmon resonance has been investigated for a perovskite solar cell. This
      dual-functional film, composed of Au nanoparticles coated on the surface of
      Y2O3:Eu3+ phosphor (Au@Y2O3:Eu3+) nanoparticle monolayer, enhances the solar
      energy conversion efficiency to electrical energy and long-term stability of
      photovoltaic cells. Coupling between the Y2O3:Eu3+ phosphor monolayer and
      ultraviolet solar light induces the latter to be converted into visible light
      with a quantum yield above 80%. Concurrently, the Au nanoparticle monolayer on
      the phosphor nanoparticle monolayer amplifies the converted visible light by up
      to 170%. This synergy leads to an increased solar light energy conversion
      efficiency of perovskite solar cells. Simultaneously, the dual-function film
      suppresses the photodegradation of perovskite by UV light, resulting in long-term
      stability. Introducing the hybrid smart Au@Y2O3:Eu3+ film in perovskite solar
      cells increases their overall solar-to-electrical energy conversion efficiency to
      16.1% and enhances long-term stability, as compared to the value of 15.2% for
      standard perovskite solar cells. The synergism between the wavelength conversion
      effect of the phosphor nanoparticle monolayer and the wave amplification by the
      localized surface plasmon resonance of the Au nanoparticle monolayer in a
      perovskite solar cell is comparatively investigated, providing a viable strategy
      of broadening the solar spectrum utilization.

PMID- 28754998
TI  - Oral exposure to arsenic causes hearing loss in young people aged 12-29 years and
      in young mice.
AB  - There is no information on the association between oral exposure to arsenic (As)
      and hearing loss in humans or mice. In this combined epidemiological study and
      experimental study, the association of oral exposure to As with hearing loss in
      people aged 12-29 years and young mice was examined. Subjects in the exposure
      group (n = 48), who were drinking tube well water contaminated with As, showed
      significantly higher risks of hearing loss at 4 kHz [odds ratio (OR) = 7.60; 95%
      confidence interval (CI): 1.56, 57.88], 8 kHz (OR = 5.00; 95% CI: 1.48, 18.90)
      and 12 kHz (OR = 8.72; 95% CI: 2.09, 47.77) than did subjects in the control
      group (n = 29). We next performed an experiment in which young mice were exposed
      to As via drinking water at 22.5 mg/L, which is a much greater concentration than
      that in human studies. The exposure group showed hearing loss and accumulation of
      As in inner ears. Ex vivo exposure of the organ of Corti from mice exposed to As
      significantly decreased the number of auditory neurons and fibers. Thus, our
      combined study showed that oral exposure to As caused hearing loss in young
      people and young mice.

PMID- 28754999
TI  - Identification of an operon involved in fluoride resistance in Enterobacter
      cloacae FRM.
AB  - Fluorine is ubiquitous and the most active non-metal element in nature. While
      many microorganisms have developed fluoride resistance as a result of the
      widespread and prolonged application of oral hygiene products, the mechanisms
      used by these organisms to overcome fluoride toxicity are incompletely
      understood. In this study, a fluoride-resistant strain, Enterobacter cloacae FRM,
      was identified which could grow well at a fluoride concentration of 4,000 mg/L.
      According to comparative genomics, transcriptome under fluoride stress, and
      sequence analyses of two fluoride-resistant fosmid clones, the genomic island GI3
      was found to be important for fluoride resistance. The result of quantitative RT
      PCR indicated that six genes on GI3, ppaC, uspA, eno, gpmA, crcB, and orf5249,
      which encode a fluoride transporter, fluoride-inhibited enzymes, and a universal
      stress protein, reside in an operon and are transcribed into two mRNAs activated
      by fluoride with a fluoride riboswitch. The results of knockout and
      complementation experiments indicated that these genes work together to provide
      high fluoride resistance to E. cloacae FRM. This study clarified the resistance
      mechanism of this high fluoride-resistant organism and has expanded our
      understanding of the biological effects of fluoride.

PMID- 28755000
TI  - Conditions for escape of a rotor in a rotary nanobearing from short triple-wall
      nanotubes.
AB  - In a short nanobearing system made from carbon nanotubes, the rotor with high
      rotational frequency may escape from the stator, which may cause a stability
      problem to the system of a nanodevice with such a nanobearing. In the present
      work, nanobearings with tri-walled nanotubes are investigated to reveal the
      conditions for the moving away of the free inner tube from the high-speed
      rotating middle tube. Experimental results show that the escape happens when the
      radii difference between the two rotors is larger than 0.34 nm and the rotational
      frequency of the middle tube is higher than a critical value. And before the
      escape occurs, the rotational frequency of the inner tube is lower than this
      critical value. Due to the radii difference being larger than 0.34 nm, the two
      rotors are non-coaxial, and the centrifugal force of the inner tube results in
      strong radial and axial interactions between the edges of the two rotors. When
      the relative sliding speed is relatively high, an edge of the inner rotor will
      pass through the potential barrier at the adjacent edge of the middle rotor, and
      further escape from the middle rotor occurs. The selection of a longer middle
      rotor with smaller radius can increase the critical rotational frequency of the
      middle rotor.

PMID- 28755001
TI  - Identification of clusters of rapid and slow decliners among subjects at risk for
      Alzheimer's disease.
AB  - The heterogeneity of Alzheimer's disease contributes to the high failure rate of
      prior clinical trials. We analyzed 5-year longitudinal outcomes and biomarker
      data from 562 subjects with mild cognitive impairment (MCI) from two national
      studies (ADNI) using a novel multilayer clustering algorithm. The algorithm
      identified homogenous clusters of MCI subjects with markedly different prognostic
      cognitive trajectories. A cluster of 240 rapid decliners had 2-fold greater
      atrophy and progressed to dementia at almost 5 times the rate of a cluster of 184
      slow decliners. A classifier for identifying rapid decliners in one study showed
      high sensitivity and specificity in the second study. Characterizing subgroups of
      at risk subjects, with diverse prognostic outcomes, may provide novel mechanistic
      insights and facilitate clinical trials of drugs to delay the onset of AD.

PMID- 28755002
TI  - Prediction of soil cadmium distribution across a typical area of Chengdu Plain,
      China.
AB  - A suitable method and appropriate environmental variables are important for
      accurately predicting heavy metal distribution in soils. However, the classical
      methods (e.g., ordinary kriging (OK)) have a smoothing effect that results in a
      tendency to neglect local variability, and the commonly used environmental
      variables (e.g., terrain factors) are ineffective for improving predictions
      across plains. Here, variables were derived from the obvious factors affecting
      soil cadmium (Cd), such as road traffic, and were used as auxiliary variables for
      a combined method (HASM_RBFNN) that was developed using high accuracy surface
      modelling (HASM) and radial basis function neural network (RBFNN) model. This
      combined method was then used to predict soil Cd distribution in a typical area
      of Chengdu Plain in China, considering the spatial non-stationarity of the
      relationships between soil Cd and the derived variables based on 339 surface soil
      samples. The results showed that HASM_RBFNN had lower prediction errors than OK,
      regression kriging (RK) and HASM_RBFNNs, which didn't consider the spatial non
      stationarity of the soil Cd-derived variables relationships. Furthermore,
      HASM_RBFNN provided improved detail on local variations. The better performance
      suggested that the derived environmental variables were effective and HASM_RBFNN
      was appropriate for improving the prediction of soil Cd distribution across
      plains.

PMID- 28755003
TI  - Kindlin-2 could influence breast nodule elasticity and improve lymph node
      metastasis in invasive breast cancer.
AB  - This study investigated the relationship between quantitative parameters of shear
      wave elastography (SWE, maximum elasticity [Emax], minimum elasticity [Emin],
      mean elasticity [Emean]), collagen intensity and Kindlin-2 expression in benign
      and malignant breast nodules, and if Kindlin-2 expression is related with lymph
      node metastasis. A total of 102 breast nodules from 102 patients were included in
      our study who underwent ultrasound elastography before surgery or core needle
      biopsy. There was a significant difference between benign and malignant breast
      nodules in Emax, Emean, collagen intensity and Kindlin-2 expression, but it had
      no difference in Emin. Collagen intensity and Kindlin-2 expression both
      correlated positively with Emax, but not with Emean. Among 38 malignant breast
      nodules, the average Emax of the metastasis group was higher than that of the non
      metastasis group, but it had no statistical significance. Compared with the non
      metastasis group, Kindlin-2 expression was considerably higher in the metastasis
      group. However, there was no difference in collagen intensity between the
      metastasis group and the non-metastasis group. In conclusion, Kindlin-2 and
      collagen might contribute to breast nodule elasticity through molecular
      mechanisms. In breast cancer, overexpression of Kindlin-2 might be a risk factor
      for lymph node metastasis.

PMID- 28755004
TI  - A simple method using ex vivo culture of hair follicle tissue to investigate
      intrinsic circadian characteristics in humans.
AB  - Almost all organisms maintain a circadian clock from birth to death to
      synchronize their own physiology and behavior with the earth's rotation. Because
      the in vivo evaluation of human circadian characteristics is labor-intensive, in
      vitro or ex vivo approaches could provide advantages. In this study, to enable
      the simple and non-invasive evaluation of autonomous circadian oscillation, we
      established a method for monitoring clock gene expression by performing ex vivo
      culture of whole hair root tissue. This method is extremely simple and imposes
      little burden on subjects. Results obtained using Cryptochrome-deficient mice
      support that circadian period length in hair tissue correlates with intrinsic
      period length observed in physiology and behavior. We then applied this method to
      old-old subjects with severe dementia, who showed abnormal circadian behavior,
      and found that their peripheral clocks autonomously oscillated in a manner
      similar to those of healthy or younger subjects, indicating that the effect of
      cellular senescence on the autonomous clock oscillator is limited at least in
      some cell types. Although further validation may be required, the hair tissue
      based culture assay would be a tool to investigate intrinsic circadian
      characteristics in humans.

PMID- 28755005
TI  - The polarization and the fundamental sensitivity of 39K (133Cs)-85Rb-4He hybrid
      optical pumping spin exchange relaxation free atomic magnetometers.
AB  - The hybrid optical pumping spin exchange relaxation free (SERF) atomic
      magnetometers can realize ultrahigh sensitivity measurement of magnetic field and
      inertia. We have studied the 85Rb polarization of two types of hybrid optical
      pumping SERF magnetometers based on 39K-85Rb-4He and 133Cs-85Rb-4He respectively.
      Then we found that 85Rb polarization varies with the number density of buffer gas
      4He and quench gas N2, pumping rate of pump beam and cell temperature
      respectively, which will provide an experimental guide for the design of the
      magnetometer. We obtain a general formula on the fundamental sensitivity of the
      hybrid optical pumping SERF magnetometer due to shot-noise. The formula describes
      that the fundamental sensitivity of the magnetometer varies with the number
      density of buffer gas and quench gas, the pumping rate of pump beam, external
      magnetic field, cell effective radius, measurement volume, cell temperature and
      measurement time. We obtain a highest fundamental sensitivity of 1.5073 aT/Hz 1/2
      (1 aT = 10-18 T) with 39K-85Rb-4He magnetometer between above two types of
      magnetometers when 85Rb polarization is 0.1116. We estimate the fundamental
      sensitivity limit of the hybrid optical pumping SERF magnetometer to be superior
      to 1.8359 * 10-2 aT/Hz 1/2, which is higher than the shot-noise-limited
      sensitivity of 1 aT/Hz 1/2 of K SERF atomic magnetometer.

PMID- 28755006
TI  - Transitions between classes of neuronal excitability and bifurcations induced by
      autapse.
AB  - Neuronal excitabilities behave as the basic and important dynamics related to the
      transitions between firing and resting states, and are characterized by distinct
      bifurcation types and spiking frequency responses. Switches between class I and
      II excitabilities induced by modulations outside the neuron (for example,
      modulation to M-type potassium current) have been one of the most concerning
      issues in both electrophysiology and nonlinear dynamics. In the present paper, we
      identified switches between 2 classes of excitability and firing frequency
      responses when an autapse, which widely exists in real nervous systems and plays
      important roles via self-feedback, is introduced into the Morris-Lecar (ML) model
      neuron. The transition from class I to class II excitability and from class II to
      class I spiking frequency responses were respectively induced by the inhibitory
      and excitatory autapse, which are characterized by changes of bifurcations,
      frequency responses, steady-state current-potential curves, and nullclines.
      Furthermore, we identified codimension-1 and -2 bifurcations and the
      characteristics of the current-potential curve that determine the transitions.
      Our results presented a comprehensive relationship between 2 classes of neuronal
      excitability/spiking characterized by different types of bifurcations, along with
      a novel possible function of autapse or self-feedback control on modulating
      neuronal excitability.

PMID- 28755007
TI  - Use of Microarray Datasets to generate Caco-2-dedicated Networks and to identify
      Reporter Genes of Specific Pathway Activity.
AB  - Intestinal epithelial cells, like Caco-2, are commonly used to study the
      interaction between food, other luminal factors and the host, often supported by
      microarray analysis to study the changes in gene expression as a result of the
      exposure. However, no compiled dataset for Caco-2 has ever been initiated and
      Caco-2-dedicated gene expression networks are barely available. Here, 341 Caco-2
      specific microarray samples were collected from public databases and from in
      house experiments pertaining to Caco-2 cells exposed to pathogens, probiotics and
      several food compounds. Using these datasets, a gene functional association
      network specific for Caco-2 was generated containing 8937 nodes 129711 edges. Two
      in silico methods, a modified version of biclustering and the new Differential
      Expression Correlation Analysis, were developed to identify Caco-2-specific gene
      targets within a pathway of interest. These methods were subsequently applied to
      the AhR and Nrf2 signalling pathways and altered expression of the predicted
      target genes was validated by qPCR in Caco-2 cells exposed to coffee extracts,
      known to activate both AhR and Nrf2 pathways. The datasets and in silico
      method(s) to identify and predict responsive target genes can be used to more
      efficiently design experiments to study Caco-2/intestinal epithelial-relevant
      biological processes.

PMID- 28755008
TI  - Biochar influences on soil CO2 and CH4 fluxes in response to wetting and drying
      cycles for a forest soil.
AB  - Biochar has been the focus of significant research efforts in agriculture, but
      little research has been conducted in forested ecosystems. Here, we assess CO2
      and CH4 fluxes from a forest soil in response to biochar additions using a before
      after-control-intervention experimental design. Soil CO2 and CH4 fluxes were
      measured over a series of wetting cycles by coupling soil mesocosms equipped with
      auto-chambers to a laser-based spectrometer for high-frequency measurements of
      gas fluxes and related soil processes. We found that soil CO2 fluxes were higher
      and CH4 fluxes were less negative (e.g. reduced CH4 uptake) for the biochar
      amended soil compared to the no biochar condition. Furthermore, biochar improved
      soil infiltrability under wet conditions, and enhanced soil moisture levels under
      dry conditions. Biochar additions shifted the point of maximum soil respiration
      (i.e. soil CO2 efflux) to a slightly wetter soil moisture level. The point of
      maximum CH4 uptake was also shifted to a slightly wetter moisture level for soil
      with biochar. Overall differences in soil gas fluxes were found to be minor
      compared to the increase in soil carbon resulting from the biochar addition.
      Biochar may thus contribute to improved forest management through increases to
      soil carbon stocks and improved soil moisture levels.

PMID- 28755009
TI  - Transcriptomic signature of the follicular somatic compartment surrounding an
      oocyte with high developmental competence.
AB  - During antral folliculogenesis, developmental competence of prospective oocytes
      is regulated in large part by the follicular somatic component to prepare the
      oocyte for the final stage of maturation and subsequent embryo development. The
      underlying molecular mechanisms are poorly understood. Oocytes reaching the
      advanced stage of follicular growth by administration of exogenous follicle
      stimulating hormone (FSH) possess higher developmental competence than oocytes in
      FSH-untreated smaller follicles. In this study, the transcriptomic profile of the
      cumulus cells from cows receiving FSH administration (FSH-priming) was compared,
      as a model of high oocyte competence, with that from untreated donor cows
      (control). Ingenuity Pathway Analysis showed that cumulus cells receiving FSH
      priming were rich in down-regulated transcripts associated with cell movement and
      migration, including the extracellular matrix-related transcripts, probably
      preventing the disruption of cell-to-cell contacts. Interestingly, the
      transcriptomic profile of up-regulated genes in the control group was similar to
      that of granulosa cells from atretic follicles. Interferon regulatory factor 7
      was activated as the key upstream regulator of FSH-priming. Thus, acquisition of
      developmental competence by oocytes can be ensured by the integrity of cumulus
      cells involved in cell-to-cell communication and cell survival, which may help
      achieve enhanced oocyte-somatic cell coupling.

PMID- 28755010
TI  - Switchable phase and polarization singular beams generation using dielectric
      metasurfaces.
AB  - Singular beams which possess helical phase wavefront or spatially inhomogeneous
      polarization provide new freedom for optical field manipulation. However,
      conventional schemes to produce the singular beams have difficulty in realizing
      the flexible switch between different singular beams. In this work, we have
      experimentally demonstrated the capability of dielectric metasurfaces to generate
      three types of singular beams and switch between them at working wavelength of
      1550  nm. We have shown vortex beam and cylindrical vector beam generation with
      single metasurface and cylindrical vector vortex beam generation with two
      cascaded metasurfaces. Moreover, experimental demonstration on switching
      cylindrical vector beam into vortex beam has also been done by combining one
      quarter-wave plate and a Glan laser polarizer. The experimental results match
      well with the analysis from the Jones matrix calculations. The average conversion
      efficiency of cylindrical vector beam to vortex beam was estimated to be 47.7%,
      which was about 2.3% lower than the theoretical prediction.

PMID- 28755011
TI  - Impact of Chiropractic Manipulation on Bone and Skeletal Muscle of Ovariectomized
      Rats.
AB  - Evidence suggests that chiropractic manipulation might exert positive effects in
      osteoporotic patients. The aim of this study was to evaluate the effects of
      chiropractic manipulation on bone structure and skeletal muscle in rats with bone
      loss caused by ovariectomy (OVX). The 6-month old Sprague-Dawley rats at 10 weeks
      following OVX or sham operation (Sh) did not suffer chiropractic manipulation (NM
      group) or were submitted to true chiropractic manipulation using the chiropractic
      adjusting instrument Activator V(r) three times/week for 6 weeks as follows:
      Force 1 setting was applied onto the tibial tubercle of the rat right hind limb
      (TM group), whereas the corresponding left hind limb received a false
      manipulation (FM group) consisting of ActivatorV(r) firing in the air and
      slightly touching the tibial tubercle. Bone mineral density (BMD) and bone
      mineral content (BMC) were determined in long bones and L3-L4 vertebrae in all
      rats. Femora and tibia were analyzed by MUCT. Mechano growth factor (MGF) was
      detected in long bones and soleus, quadriceps and tibial muscles by
      immunohistochemistry and Western blot. The decrease of BMD and BMC as well as
      trabecular bone impairment in the long bones of OVX rats vs Sh controls was
      partially reversed in the TM group versus FM or NM rats. This bone improvement by
      chiropractic manipulation was associated with an increased MGF expression in the
      quadriceps and the anterior tibial muscle in OVX rats. These findings support the
      notion that chiropractic manipulation can ameliorate osteoporotic bone at least
      partly by targeting skeletal muscle.

PMID- 28755012
TI  - Perceptual similarity induces overinvestment in an attentional blink task.
AB  - The overinvestment account of the attentional blink (AB) posits that the AB
      results from the allocation of more resources than necessary to encode a first
      target (T1), which in turn lowers the resources available to encode a second
      target (T2) shortly thereafter. Across two experiments, we examined whether
      resource allocation to T1, and thus overinvestment that results in an AB effect,
      might be limited by perceptual mechanisms that evaluate the need for encoding
      resources. The key result observed in both experiments was that a relatively easy
      to encode T1 can nonetheless result in an AB when it is perceptually similar to a
      more difficult to encode T1. The importance of experimental context as an
      influence on the allocation, or overinvestment, of attentional resources to T1 is
      highlighted by these findings.

PMID- 28755013
TI  - Boys with Oppositional Defiant Disorder/Conduct Disorder Show Impaired Adaptation
      During Stress: An Executive Functioning Study.
AB  - Evidence for problems in executive functioning (EF) in children with oppositional
      defiant disorder/conduct disorder (ODD/CD) is mixed and the impact stress may
      have on EF is understudied. Working memory, sustained attention, inhibition and
      cognitive flexibility of boys with ODD/CD (n = 65) and non-clinical controls (n =
      32) were examined under typical and stressful test conditions. Boys with ODD/CD
      showed impaired working memory under typical testing conditions, and impairments
      in working memory and sustained attention under stressful conditions. In contrast
      to controls, performance on sustained attention, cognitive flexibility and
      inhibition was less influenced by stress in boys with ODD/CD. These results
      suggest that boys with ODD/CD show impairments in adaptation to the environment
      whereas typically developing boys show adaptive changes in EF.

PMID- 28755014
TI  - Significance of glucocorticoid receptor expression in patients with non-small
      cell lung cancer treated with pemetrexed-based chemotherapy.
AB  - BACKGROUND: Pemetrexed is the preferred chemotherapy agent in the management of
      non-squamous non-small cell lung cancer (non-sq-NSCLC), but lacks biomarkers
      predicting its efficacy. Dexamethasone, one of the premedications of pemetrexed,
      may downregulate p53 through the glucocorticoid receptor (GR). The purpose of our
      study was to explore the effect of GR in peripheral blood mononuclear cells
      (PBMC) and its role in predicting pemetrexed efficacy. METHODS: In all, 122
      patients with stage IV non-sq-NSCLC who received first-line pemetrexed-containing
      chemotherapy were retrospectively reviewed. The expression of GR in PBMC was
      measured before treatment with pemetrexed using real-time PCR was used to detect
      the levels of GRalpha and GRbeta. RESULTS: The response rate for all patients was
      38.5%, with a median progression-free survival (PFS) of 5.9 months and overall
      survival (OS) of 14.3 months. In univariate analyses, patients with a low
      GRalpha/GRbeta ratio in PBMC had higher RR, better PFS, and better OS than those
      with a high GRalpha/GRbeta ratio (RR: 48.2 vs. 30.3%, p = 0.043; mPFS: 6.9 vs.
      4.0 months, p < 0.001; mOS: 18.7 vs. 12.2 months, p = 0.005). The baseline
      GRalpha/GRbeta ratio was an independent factor for RR (odds ratio [OR] = 0.451,
      95% CI 0.208-0.978; p = 0.044), PFS (HR = 1.584, 95% CI 1.094-2.295; p = 0.015),
      and OS (HR = 1.761, 95% CI 1.195-2.595; p = 0.004). CONCLUSIONS: Baseline
      GRalpha/GRbeta ratio in PBMC may play a role in predicting the efficacy of first
      line pemetrexed-containing chemotherapy in stage IV non-sq NSCLC patients.

PMID- 28755015
TI  - ?

PMID- 28755016
TI  - Numerical investigation of oxygen transport by hemoglobin-based carriers through
      microvessels.
AB  - The small size of hemoglobin-based oxygen carriers (HBOCs) may expand the realm
      of new treatment possibilities for various circulatory diseases. The parametric
      evaluation of HBOC performance for oxygen transport within tissue is essential
      for effectively characterizing its performance for each circulatory disease
      assessed. Thus, the overarching objective of this present study was to
      numerically investigate the reaction-diffusion phenomenon of oxygenated HBOCs and
      oxygen on tissues through microvessels. We considered dissociation rate
      coefficients, oxygen affinity, and diffusion coefficients due to Brownian motion
      as the biophysical parameters for estimating HBOC performance for oxygen
      transport. A two-dimensional computational domain, including vessel and tissue
      regions, was, therefore, accordingly assumed. It was observed that HBOC flows in
      a microvessel with a diameter of 25 MUm and a length of 1 mm, and that the
      dissociated oxygen diffuses to the tissue region. The results indicated that
      oxyhemoglobin saturation and partial oxygen tension in a downstream region
      changed according to each biophysical parameter of HBOC. Moreover, the change in
      oxygen consumption rate in the tissue region had considerable influence on the
      oxyhemoglobin saturation level within the vessel. Comparison between simulation
      results and existing in vitro experimental data of actual HBOCs and RBC showed
      qualitatively good agreement. These results provide important information for the
      effective design of robust HBOCs in future.

PMID- 28755017
TI  - Investigation of the influence of fluid dynamics on thrombus growth at the
      interface between a connector and tube.
AB  - Thrombus formation at the interface between connectors and tubes is a potential
      risk factor for complications. We investigated time-dependent relationships
      between formation of thrombus and hemodynamic factors at the interface between
      connectors and tubes using optical coherence tomography (OCT) under pulsatile
      flow. A swept-source OCT with the center wavelength of 1330 nm was employed. The
      sequential process of thrombus formation at the interface of connectors and tubes
      in the inlet and outlet was investigated. Connectors with and without tapers were
      tested using identical 50-ml air-contactless circuits. Fresh human blood from
      healthy volunteers was circulated under pulsatile flow. Thrombus initially formed
      at the interface between the connector tip and the tube. Geometries of thrombus
      growth were different between the 2 connectors, and between the inlet and the
      outlet. Growth of thrombus was observed at the interface between the connectors
      and tubes over time in 60 min circulation, except at the outlet part of connector
      without tapers. At the connector without tapers outlet, thrombus propagation
      length from the connector edge toward the flow downstream was comparable at 10
      and 60 min (0.55 +/- 0.35 vs. 0.51 +/- 0.32 mm, p = 0.83). Analysis using
      particle image velocimetry showed the presence of a flow reattachment point 1.5
      mm downstream from the connector edge. These results suggest that the flow
      reattachment point inhibits downstream thrombus growth. We quantitatively
      demonstrated sequential thrombus process at the interface between the connectors
      and tubes under pulsatile flow of human blood using OCT.

PMID- 28755018
TI  - Outcomes of nonsurgical versus surgical treatment of cesarean scar pregnancies in
      the first trimester.
AB  - PURPOSE: To compare outcomes of nonsurgical versus surgical treatment of Cesarean
      scar pregnancies (CSP) in the first trimester and identify optimal treatment
      methods for CSP. METHODS: Retrospective cohort study of all women diagnosed and
      treated with CSP in the first trimester at a single tertiary care center from
      2000-2012. Main outcome measures were need for additional treatments, hemorrhage,
      or emergent hysterectomy. Future pregnancy outcomes were considered secondarily.
      RESULTS: Twenty-three cases of CSP treated in the first trimester were confirmed
      including 12 treated surgically and 11 treated nonsurgically. Of the nonsurgical
      patients, none treated with a combination of intrasac potassium chloride (KCl)
      and systemic methotrexate (MTX) required further treatment versus 5/8 (62%) of
      those treated with a single agent (p = 0.18). One patient who was treated with
      intrasac KCl alone experienced hemorrhage. Of the nine patients treated with
      suction dilation and curettage (D&C), two (22%) required additional intervention,
      but none experienced major complications. Nonsurgical therapy had a higher rate
      of needing further intervention (45%) than surgical therapy (17%) (p = 0.19).
      There was one recurrent CSP in 11 subsequent deliveries with no uterine ruptures
      or hysterectomies. CONCLUSIONS: We have described nonsurgical and surgical
      treatments of first trimester CSP with a low rate of major complications and no
      emergent hysterectomies. Of the nonsurgical therapies, single-agent treatment
      with either systemic MTX or intrasac KCl was associated with high rates of
      needing additional treatment and should be avoided. Our method of ultrasound
      guided suction D&C resulted in no major hemorrhage and is a reasonable surgical
      treatment option.

PMID- 28755019
TI  - Turning a blind eye: HTLV-1-associated uveitis in Indigenous adults from Central
      Australia.
AB  - PURPOSE: We describe the first two cases of HTLV-1 associated uveitis to be
      associated with HTLV-1c subtype infection. METHODS: Case report. RESULTS: Uveitis
      was demonstrated in two Indigenous Australian men, both of whom had high HTLV-1c
      proviral loads in peripheral blood. Visual outcomes were poor in each case.
      CONCLUSION: Clinicians should be aware of HTLV-1c infection as a cause of uveitis
      in Australia, and HTLV-1 serology should be included in the basic uveitis work-up
      in HTLV-1-endemic areas.

PMID- 28755020
TI  - An unusual cause of vertigo and headache in childhood.
AB  - Spinal perimedullary arteriovenous fistulas (PMAVFs) are rare entities among
      vascular malformations of the spinal cord. Due to progressive myelopathy, spastic
      paresis, sensory disturbance, and bowl and bladder dysfunction can be the
      presenting symptoms. Cervical spinal arteriovenous fistulas (AVFs) are even
      rarer. These lesions differ from the ones in the thoracolumbar region and have an
      even wider mode of presentation. We report on a 9-year-old boy with a cervical
      PMAVF manifesting with headache and vertigo.

PMID- 28755021
TI  - A regularized variable selection procedure in additive hazards model with
      stratified case-cohort design.
AB  - Case-cohort designs are commonly used in large epidemiological studies to reduce
      the cost associated with covariate measurement. In many such studies the number
      of covariates is very large. An efficient variable selection method is needed for
      case-cohort studies where the covariates are only observed in a subset of the
      sample. Current literature on this topic has been focused on the proportional
      hazards model. However, in many studies the additive hazards model is preferred
      over the proportional hazards model either because the proportional hazards
      assumption is violated or the additive hazards model provides more relevent
      information to the research question. Motivated by one such study, the
      Atherosclerosis Risk in Communities (ARIC) study, we investigate the properties
      of a regularized variable selection procedure in stratified case-cohort design
      under an additive hazards model with a diverging number of parameters. We
      establish the consistency and asymptotic normality of the penalized estimator and
      prove its oracle property. Simulation studies are conducted to assess the finite
      sample performance of the proposed method with a modified cross-validation tuning
      parameter selection methods. We apply the variable selection procedure to the
      ARIC study to demonstrate its practical use.

PMID- 28755022
TI  - Interatrial septum versus right atrial appendage pacing for prevention of atrial
      fibrillation : A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Interatrial septum (IAS) pacing seems to be a promising strategy for
      the prevention of atrial fibrillation (AF); however, studies have yielded
      conflicting results. This meta-analysis was to compare IAS with right atrial
      appendage (RAA) pacing on the prevention of postpacing AF occurrence. METHODS:
      Pubmed, MEDLINE, EMBASE and Web of Science databases were searched through
      October 2016 for randomized controlled trials comparing IAS with RAA pacing on
      the prevention of AF. Data concerning study design, patient characteristics and
      outcomes were extracted. Risk ratio (RR), weighted mean differences (WMD) or
      standardized mean differences (SMD) were calculated using fixed or random effects
      models. RESULTS: A total of 12 trials involving 1146 patients with dual-chamber
      pacing were included. Although IAS was superior to RAA pacing in terms of
      reducing the number of AF episodes (SMD = -0.29, P = 0.05), AF burden (SMD = 
      0.41, P = 0.008) and P -wave duration (WMD = -34.45 ms, P < 0.0001), neither
      permanent AF occurrence (RR = 0.94, P = 0.58) nor recurrences of AF (RR = 0.88, P
      = 0.36) were reduced by IAS pacing. Nevertheless, no differences were observed
      concerning all-cause death (RR = 1.04, P = 0.88), procedure-related events (RR =
      1.17, P = 0.69) and pacing parameters between IAS and RAA pacing in the follow-up
      period. CONCLUSIONS: IAS pacing is safe and as well tolerated as RAA pacing.
      Although IAS pacing may fail to prevent permanent AF occurrence and recurrences
      of AF, it is able to not only improve interatrial conduction, but also reduce AF
      burden.

PMID- 28755023
TI  - The impact of cumulative dose of cisplatin on outcome of patients with head and
      neck squamous cell carcinoma.
AB  - Despite the wide use of cisplatin-based concomitant chemoradiotherapy (CCRT) for
      head and neck squamous cell carcinoma (HNSCC), data on the optimal regimen and
      cumulative dose are scarce and frequently conflicting. We aimed to evaluate the
      compliance and the impact of the cumulative dose of cisplatin on overall survival
      (OS), disease-free survival (DFS), loco-regional control (LRC), and distant
      metastasis-free survival (DMFS) in a retrospective study. Between 2008 and 2015,
      279 patients with HNSCC scheduled for CCRT (three courses of 3-week 100 mg/m2
      cisplatin) were identified. Of the whole group, 14% did not receive any cisplatin
      and 26% received daily cisplatin. In patients planned for three courses (n =
      167), 56% received 3, 20% received 2, and 24% received one course. After median
      follow-up of 31.6 months, the actuarial OS, DFS, LRC, and DMFS rates at 3 years
      for patients received cumulative dose of >=200 mg/m2 were significantly better
      compared to those received <200 mg/m2; 74 vs. 51% for OS, 73 vs. 49% for DFS, 80
      vs. 58% for LRC (p < 0.001), and 85 vs. 76% for DMFS (p = 0.034). At multivariate
      analysis, the cumulative cisplatin dose (>=200 vs. <200 mg/m2) was significantly
      predictive for OS (HR 2.05; 95% CI 1.35-3.13, p = <0.001). Borderline GFR (60-70
      mL/min) at baseline predicts compliance for >=two courses (p = 0.003). In
      conclusion, considerable proportion of patients did not receive all pre-planned
      courses of cisplatin. Patients receiving cumulative cisplatin dose >=200 mg/m2
      had significantly better outcome than those receiving <200 mg/m2 and cumulative
      dose <200 mg/m2 might even be detrimental. These findings increased the bulk of
      slowly growing evidence on the optimal cumulative dose of cisplatin. Baseline GFR
      might predict compliance.

PMID- 28755024
TI  - Concentration of acute phase factors in vitreous fluid in diabetic macular edema.
AB  - PURPOSE: Diabetic retinal maculopathy is associated with acute and chronic local
      inflammation. We measured the concentrations of acute phase factors in vitreous
      fluid of patients with diabetic macular edema (DME) and examined their relations
      to visual acuity and central retinal thickness (CRT) both before and after
      vitrectomy. STUDY DESIGN: Retrospective. METHODS: Vitreous fluid was collected
      during vitreoretinal surgery from 19 patients with DME and 12 control subjects
      with epiretinal membrane. The concentrations of acute phase factors (alpha2
      macroglobulin, haptoglobin, C-reactive protein, serum amyloid P and A,
      procalcitonin, ferritin, tissue plasminogen activator, fibrinogen) and vascular
      endothelial growth factor (VEGF) were measured with multiplex assays. CRT of
      macular edema was measured by optical coherence tomography (OCT). RESULTS: The
      levels of serum amyloid P, procalcitonin, ferritin, and fibrinogen in vitreous
      fluid were increased in DME patients compared with control subjects. The levels
      of procalcitonin and fibrinogen in DME patients were inversely correlated with
      visual acuity both before and 3 months after vitrectomy but not 6 months
      postsurgery. The concentrations of these four factors were not correlated with
      either CRT or the vitreous levels of VEGF in DME patients. CONCLUSION: Acute
      phase factors may contribute to local inflammation in DME and may therefore
      influence disease progression.

PMID- 28755025
TI  - Inflammatory Bowel Disease in Primary Immunodeficiencies.
AB  - PURPOSE OF REVIEW: Inflammatory bowel disease is most often a polygenic disorder
      with contributions from the intestinal microbiome, defects in barrier function,
      and dysregulated host responses to microbial stimulation. There is, however,
      increasing recognition of single gene defects that underlie a subset of patients
      with inflammatory bowel disease, particularly those with early-onset disease, and
      this review focuses on the primary immunodeficiencies associated with early-onset
      inflammatory bowel disease. RECENT FINDINGS: The advent of next-generation
      sequencing has led to an improved recognition of single gene defects underlying
      some cases of inflammatory bowel disease. Among single gene defects, immune
      response genes are the most frequent category identified. This is also true of
      common genetic variants associated with inflammatory bowel disease, supporting a
      pivotal role for host responses in the pathogenesis. This review focuses on
      practical aspects related to diagnosis and management of children with
      inflammatory bowel disease who have underlying primary immunodeficiencies.

PMID- 28755026
TI  - Sensitivity of Enzymatic Toxins from Corneal Isolate of Acanthamoeba Protozoan to
      Physicochemical Parameters.
AB  - Acanthamoeba is a free-living amoeba that causes severe corneal infection
      (Acanthamoeba keratitis) and produces a variety of extracellular enzymes, called
      exoproteome. Since physicochemical characters are suggested being associated with
      therapeutic profile and clinical severity of the infection, we investigated the
      physicochemical properties of proteolysis mediated by amoebic exoproteome.
      Corneal scraping was collected from a patient who showed typical symptoms of
      acute Acanthamoeba keratitis. Axenic amoeba was phylogenetically identified by
      18S rDNA sequencing analysis. Effects of pH, temperature and diamidines on
      proteolysis mediated by exoproteome were assessed using zymography assays.
      Proteolytic enzymes were most active at pH 7.0 and 37  degrees C. Calcium ions
      decreased enzymatic activity. The main components of amoebic exoproteome were
      characterized as serine proteases. We demonstrated for the first time that
      commercial antimicrobial diamidines used for Acanthamoeba keratitis therapy
      inhibit enzymatic activity of amoebic exoproteome. Results showed the
      thermostability of Acanthamoeba proteases, which suggest a long-term effect of
      these virulence factors at the central and peripheral cornea with possible role
      in degradation of extracellular matrix components. Our findings open new
      perspectives about the complementary and unreported properties of antimicrobial
      compounds of the diamidine class on the inhibition of enzymatic activity and
      presumptive control of amoebic infection in the cornea.

PMID- 28755027
TI  - Genetic Structure of the Rice Blast Pathogen (Magnaporthe oryzae) over a Decade
      in North Central California Rice Fields.
AB  - Rice blast, caused by the ascomycete Magnaporthe oryzae, is one of the most
      destructive rice diseases worldwide. Even though the disease has been present in
      California since 1996, there is no data for the pathogen population biology in
      the state. Using amplified fragment length polymorphisms and mating-type markers,
      the M. oryzae population diversity was investigated using isolates collected when
      the disease was first established in California and isolates collected a decade
      later. While in the 1990 samples, a single multilocus genotype (MLG) was
      identified (MLG1), over a decade later, we found 14 additional MLGs in the 2000
      isolates. Some of these MLGs were found to infect the only rice blast-resistant
      cultivar (M-208) available for commercial production in California. The same
      samples also had a significant decrease of MLG1. MLG1 was found infecting the
      resistant rice cultivar M-208 on one occasion whereas MLG7 was the most common
      genotype infecting the M-208. MLG7 was identified in the 2000 samples, and it was
      not present in the M. oryzae population a decade earlier. Our results demonstrate
      a significant increase in genotypic diversity over time with no evidence of
      sexual reproduction and suggest a recent introduction of new virulent race(s) of
      the pathogen. In addition, our data could provide information regarding the
      durability of the Pi-z resistance gene of the M-208. This information will be
      critical to plant breeders in developing strategies for deployment of other rice
      blast resistance genes/cultivars in the future.

PMID- 28755028
TI  - Erratum to: Serious adverse events after HPV vaccination: a critical review of
      randomized trials and post-marketing case series.

PMID- 28755029
TI  - Metastatic malignant PEComa of the leg with identification of ATRX mutation by
      next-generation sequencing.

PMID- 28755030
TI  - The human vascular endothelial cell line HUV-EC-C harbors the integrated HHV-6B
      genome which remains stable in long term culture.
AB  - Human herpes virus 6 (HHV-6) is a common human pathogen that is most often
      detected in hematopoietic cells. Although human cells harboring chromosomally
      integrated HHV-6 can be generated in vitro, the availability of such cell lines
      originating from in vivo tissues is limited. In this study, chromosomally
      integrated HHV-6B has been identified in a human vascular endothelial cell line,
      HUV-EC-C (IFO50271), derived from normal umbilical cord tissue. Sequence analysis
      revealed that the viral genome was similar to the HHV-6B HST strain. FISH
      analysis using a HHV-6 DNA probe showed one signal in each cell, detected at the
      distal end of the long arm of chromosome 9. This was consistent with a digital
      PCR assay, validating one copy of the viral DNA. Because exposure of HUV-EC-C to
      chemicals did not cause viral reactivation, long term cell culture of HUV-EC-C
      was carried out to assess the stability of viral integration. The growth rate was
      altered depending on passage numbers, and morphology also changed during culture.
      SNP microarray profiles showed some differences between low and high passages,
      implying that the HUV-EC-C genome had changed during culture. However, no
      detectable change was observed in chromosome 9, where HHV-6B integration and the
      viral copy number remained unchanged. Our results suggest that integrated HHV-6B
      is stable in HUV-EC-C despite genome instability.

PMID- 28755031
TI  - Interspecies differences in plasma concentrations of 25-hydroxyvitamin D3 and
      dermal Vitamin D synthesis of kiwi (Apteryx mantelli), tuatara (Sphenodon
      punctatus), and New Zealand sea lions (Phocarctos hookeri).
AB  - Vitamin D plays a central role in calcium homeostasis of most vertebrates, and is
      obtained in different species through diet, dermal synthesis, or a combination of
      both. The aim of this study was to determine the predominant routes of Vitamin D
      synthesis in three disparate species, brown kiwi (Apteryx mantelli), tuatara
      (Sphenodon punctatus), and New Zealand sea lions (Phocarctos hookeri). We
      surveyed plasma concentrations of 25-hydroxyvitamin D2 and D3, analysed
      environmental conditions and life history factors, and determined the ability of
      skin samples to synthesise Vitamin D3 on exposure to ultraviolet-B radiation.
      There was variation in the plasma/serum 25-hydroxyvitamin D3 concentrations
      between and within the species studied, with wild kiwi having the lowest
      concentrations and NZ sea lions the highest. Kiwi skin produced small but
      measurable amounts of Vitamin D3, while tuatara skin produced Vitamin D3
      concentrations higher than that of kiwi. New Zealand sea lion skin produced the
      highest amount of Vitamin D3 and differed from the other two species in this
      study in that Vitamin D3 was present in skin before UV-B exposure. The results
      from this study show that all three species studied retained the ability to use
      both dietary and dermal sources of Vitamin D, although there was interspecies
      variation in the magnitude of dermal synthesis. Comparisons between these species
      show that there are differences in their Vitamin D pathways, but suggest that
      there are more factors contributing to these pathways than might be expected
      solely from life history characteristics.

PMID- 28755032
TI  - Diagnosing ASD in Adults Without ID: Accuracy of the ADOS-2 and the ADI-R.
AB  - Diagnosing autism spectrum disorder (ASD) in adulthood often represents a
      challenge in clinical practice. The aim of the present study was to evaluate the
      sensitivity and specificity of the ADOS and ADI-R in diagnosing ASD in adults.
      113 subjects with an IQ of 70 or above were assessed through an extensive
      clinical evaluation. The ADOS-2 Module 4 and the ADI-R were separately
      administered by staff members blind to clinical judgment. Our results cautiously
      confirm the accuracy of ADOS-2 Module 4, while suggest that ADI-R might not be
      reliable in adults without intellectual disability. Clinicians' training and
      experience remains of primary importance while assessing adults who could
      potentially belong to the autism spectrum.

PMID- 28755033
TI  - The Actions and Feelings Questionnaire in Autism and Typically Developed Adults.
AB  - Impaired motor cognition may underpin empathy problems in autism. The actions and
      feelings questionnaire (AFQ), designed to examine individual differences in motor
      cognition, was completed fully by 1391 adults, of whom 326 reported a diagnosis
      of an autism spectrum condition (ASC). A confirmatory factor analysis supported a
      3 factor model. The AFQ total and 'feelings' subscale scores correlated highly
      with the EQ and ROC curves were similar. Our findings suggest that individual
      differences in empathic traits are heavily accounted for by variance in
      mechanisms that serve sensorimotor learning (motor cognition) in relation to
      emotional states. The AFQ is a self-report tool that provides a valid indicator
      of autism status in adult populations.

PMID- 28755034
TI  - Proneness to Self-Conscious Emotions in Adults With and Without Autism Traits.
AB  - Self-conscious emotions, such as shame, guilt and pride, facilitate our social
      interactions by motivating us to adhere to social norms and external standards.
      In this study, we examined proneness to shame, guilt, hubristic pride and
      authentic pride in adults with Autism Spectrum Disorder traits (ASD-T) and in
      neurotypical (NT) adults. Relations between proneness to self-conscious emotions
      and theory of mind (ToM), fear of negative evaluation, and social functioning
      were also assessed. Adults with ASD-T showed greater proneness to shame, and less
      proneness to guilt and pride than NT adults. Both ToM and fear of negative
      evaluation predicted proneness to self-conscious emotions in ASD-T. These
      findings are discussed in terms of understanding complex emotion processing in
      adults with ASD-T.

PMID- 28755035
TI  - Brief Report: What Happens When I Can No Longer Support My Autistic Relative?
      Worries About the Future for Family Members of Autistic Adults.
AB  - Very little is known about autism and adulthood. Family members are often the
      primary support for autistic adults and frequently express concerns about what
      the future will hold and what support will be available for their relative. 120
      family members of autistic adults completed an online survey exploring concerns
      about the future for their relative. The most endorsed concerns were "their needs
      won't be met" (77% worried weekly), "whether they will be happy" (72% worried
      weekly) and "who will care for them" (58% worried weekly). The results highlight
      the importance of implementing structured and timely support through
      collaboration with governmental policy, local commissioning and communication
      with charities to help prepare family members and their autistic relative for the
      future.

PMID- 28755036
TI  - A pilot study for segmentation of pharyngeal and sino-nasal airway subregions by
      automatic contour initialization.
AB  - PURPOSE: The objective of the present study is to put forward a novel automatic
      segmentation algorithm to segment pharyngeal and sino-nasal airway subregions on
      3D CBCT imaging datasets. METHODS: A fully automatic segmentation of sino-nasal
      and pharyngeal airway subregions was implemented in MATLAB programing
      environment. The novelty of the algorithm is automatic initialization of contours
      in upper airway subregions. The algorithm is based on boundary definitions of the
      human anatomy along with shape constraints with an automatic initialization of
      contours to develop a complete algorithm which has a potential to enhance utility
      at clinical level. Post-initialization; five segmentation techniques: Chan-Vese
      level set (CVL), localized Chan-Vese level set (LCVL), Bhattacharya distance
      level set (BDL), Grow Cut (GC), and Sparse Field method (SFM) were used to test
      the robustness of automatic initialization. RESULTS: Precision and F-score were
      found to be greater than 80% for all the regions with all five segmentation
      methods. High precision and low recall were observed with BDL and GC techniques
      indicating an under segmentation. Low precision and high recall values were
      observed with CVL and SFM methods indicating an over segmentation. A Larger F
      score value was observed with SFM method for all the subregions. Minimum F-score
      value was observed for naso-ethmoidal and sphenoidal air sinus region, whereas a
      maximum F-score was observed in maxillary air sinuses region. The contour
      initialization was more accurate for maxillary air sinuses region in comparison
      with sphenoidal and naso-ethmoid regions. CONCLUSION: The overall F-score was
      found to be greater than 80% for all the airway subregions using five
      segmentation techniques, indicating accurate contour initialization. Robustness
      of the algorithm needs to be further tested on severely deformed cases and on
      cases with different races and ethnicity for it to have global acceptance in
      Katradental radKatraiology workflow.

PMID- 28755037
TI  - Novel CD137 Gene Polymorphisms and Susceptibility to Ischemic Stroke in the
      Northern Chinese Han Population.
AB  - Ischemic stroke is a leading cause of mortality and morbidity worldwide, and
      atherosclerosis is one of the major risk factors for this neurologic deficit.
      Recent studies have revealed the important role of CD137 in human
      atherosclerosis. Here, we analyzed the association of CD137 single nucleotide
      polymorphisms (SNPs) with ischemic stroke. We assessed three SNPs (rs161827,
      rs161818, and rs161810) of the CD137 gene and their association with ischemic
      stroke in a northern Chinese Han population. A total of 496 ischemic stroke
      patients and 486 gender-matched control subjects were genotyped. We classified
      these patients according to complications with diabetes and hypertension and also
      by ischemic stroke subtypes. Allele, genotype, and haplotype association studies
      were tested in all patients and subgroups. We used multivariable logistic
      regression analysis combined with 10,000 permutations to analyze the association
      of CD137 polymorphisms with ischemic stroke. After adjusting for relevant
      factors, rs161827 was significantly different between patients with and without
      diabetes and the control group (p = 0.0001, p = 0.014, and p = 0.0001,
      respectively). In addition, rs161818 and rs161810 differed significantly between
      patients without diabetes and the control subjects (p = 0.0001 and p = 0.004,
      respectively). rs161827, rs161818, and rs161810 were all statistically
      significant among the combination stroke subgroup compared with the controls.
      These results indicate that the CD137 gene is associated with risk of ischemic
      stroke in the northern Han Chinese. Moreover, CD137 gene polymorphism may be one
      mediating factor between diabetes and ischemic stroke.

PMID- 28755038
TI  - Experimental Autoimmune Encephalomyelitis Ameliorated by Passive Transfer of
      Polymerase 1-Silenced MOG35-55 Lymphatic Node Cells: Verification of a Novel
      Therapeutic Approach in Multiple Sclerosis.
AB  - In the current study, we present an innovative concept based on the knowledge
      that enhancing naturally occurring biological mechanisms is effective in
      preventing neuronal damage and maintaining low disease activity in about 15% of
      multiple sclerosis (MS) patients presenting the benign type of MS. Recently, we
      have demonstrated that low disease activity in benign MS is associated with
      suppression of RNA polymerase 1 (POL1) pathway; therefore, targeting POL1
      transcription machinery as a strategy for suppressing active forms of MS is
      suggested. To further establish our approach, we aimed to suppress POL1 pathway
      by silencing of the POL1-related RRN3, POLR1D and LRPPRC genes in specific MOG35
      55-activated lymphocytes and assess their capacity to induce experimental
      autoimmune encephalomyelitis (EAE) by passive transfer. We have demonstrated that
      silencing of specific POL1 pathway-related genes significantly decreased
      viability and increased the proportion of CD4+/AnnexinV+/PI+ apoptotic cells in
      MOG35-55-primed lymphocytes. POL1-gene silencing significantly decreased the
      proportion of CD4+IL17+ and increased proportion of CD4+IL10+ and CD4+TNFa+
      lymphocytes that occurred simultaneously with over-presentation of Treg
      CD4+CD25+FoxP3+ cells. Passive transfer of MOG35-55-primed lymphocytes after POL1
      gene silencing suppressed EAE development in mice as demonstrated by delayed
      onset and peak of disease accompanied by significantly lower maximal and
      cumulative EAE scores. Our study supports a basis for direct targeting of POL1
      transcription pathway as a strategy for selective induction of apoptosis and
      suppression of inflammation in EAE and consequently paves the way for innovative
      and targeted MS therapeutic strategy that is based on naturally existing
      biological mechanism.

PMID- 28755039
TI  - Differential Predictors of Postpartum Depression and Anxiety: The Edinburgh
      Postnatal Depression Scale Hebrew Version Two Factor Structure Construct
      Validity.
AB  - Objectives Postpartum anxiety (PPA) is as prevalent and disruptive as postpartum
      depression (PPD), although less commonly addressed. The Edinburgh Postnatal
      Depression Scale (EPDS), originally created to screen for PPD, was found to
      include anxiety and depression subscales. This study examined the construct
      validity of the EPDS PPD and PPA subscales by examining differential predictors
      of both in a structural regression model. Methods Women (n = 969) were recruited
      from a maternity ward in Jerusalem, Israel and completed a demographic survey;
      715 (74%) women were screened for PPD and PPA at 6 weeks postpartum using the
      EPDS. Results History of depression was a significant predictor of PPD symptoms
      and PPA symptoms. Income and number of past pregnancies were significant
      predictors of PPA symptoms. Conclusions for practice PPD and PPA have different
      predictors, suggesting that the EPDS depression and anxiety subscales should be
      scored separately. Further assessment and treatment should be tailored to
      specific symptoms of depression and/or anxiety reported.

PMID- 28755040
TI  - Salmon Bias and Preterm Birth Among Western Immigrants in China.
AB  - Introduction Immigrants from Western industrialized countries are rarely found in
      immigrant studies. Our primary objective was to calculate the rate of cesarean
      delivery, 5-min Apgar score <7, and preterm birth among Chinese and Western
      women. Our secondary objective was to examine whether there are significant
      differences in terms of risk factors between Western immigrants who chose to
      deliver in their country of citizenship compared to those who chose to deliver in
      China. Methods Single-center retrospective cohort study in Shanghai, China.
      Multivariate logistic regression models used delivery outcome, and place of
      delivery (China vs. country of citizenship) as outcome variables. Results Preterm
      birth occurred at a rate of 3.82% among Chinese citizens, 4.12% among Chinese
      born Western citizens, and 6.54% among non-Chinese-born Western citizens. After
      adjustment, preterm birth <37 weeks was more frequent among non-Chinese-born
      Western citizens compared with Chinese citizens, with an odds ratio of 1.82
      (Confidence Interval 1.20-2.78), p = 0.005. Variables statistically associated
      with giving birth in China were maternal age >=35 years and being Chinese-born
      Western, as well as the absence of medical or obstetrical conditions. Discussion
      Western immigrants have overall good obstetrical outcomes in China, and this
      could be partly explained by selective immigration, but also by the Salmon bias,
      as women with risk factors tend to return to their country of citizenship for the
      delivery. However, the preterm birth rate was higher among Western women than in
      their Chinese counterparts, and further research is needed.

PMID- 28755041
TI  - The Impact of Sex of Child on Breastfeeding in the United States.
AB  - Background Sex of child has been shown to impact breastfeeding duration in India,
      Australia, Scandinavia, Latin America, and, within the US, in a sample in Eastern
      Connecticut and in a separate sample of Indian and Chinese immigrants. Objectives
      The objective of this study is to examine differences in breastfeeding initiation
      and duration by sex of child across racial/ethnic groups in the US. Methods We
      used the Pregnancy Risk Assessment Monitoring System 2009-2010 and logistic
      regression to examine whether sex of child impacts breastfeeding initiation and
      duration for at least 8 weeks by women's racial/ethnic group. Results Among the
      66,107 women in our sample representing 12 different race/ethnic groups, Hispanic
      women (n = 9049) had lower odds of breastfeeding initiation (adjusted odds ratio
      [AOR] = 0.81, 95% CI 0.71-0.93) and breastfeeding duration (AOR = .87, 95% CI
      0.80-0.96) if they have sons compared to Hispanic women who have daughters. Sex
      of child did not impact the odds of breastfeeding initiation or duration among
      any other race/ethnic group. Conclusion We have shown that, for Hispanics in the
      US, sex of child may have an impact on breastfeeding, a health behavior that has
      a variety of positive impacts on infants throughout their lives. Boys, relative
      to girls, were at a disadvantage in breastfeeding initiation and duration. Future
      work is necessary to unpack the mechanisms behind these findings. In particular,
      how sex of child impacts how mothers and fathers view the nutritional needs of
      their children and breastfeeding more broadly.

PMID- 28755042
TI  - Replicating Evidence-Based Practices with Flexibility for Perinatal Home Visiting
      by Paraprofessionals.
AB  - : Introduction Strategies are needed to improve the efficacy of paraprofessional
      home visitors for pregnant women in the United States. This study evaluates the
      maternal and child outcomes when evidence-based practices (EBP) are replicated
      with flexibility, rather than fidelity to a manualized intervention. Methods
      Pregnant mothers (N = 203) in five clinics were recruited in the waiting rooms
      and randomized to standard clinic care as the control condition (n = 104) or
      standard care plus home visiting (n = 99). Home visitors (n = 9) were selected,
      trained in foundational skills common to EBP and four problem domains (weight
      control, breastfeeding, daily habits, and depression). Independent interviewers
      assessed targeted outcomes at birth (82%) and 6 months later (83%). RESULTS: Home
      visitors, called Mentor Mothers [MM], made an average of 14.9 home visits or
      telephone contacts (SD = 9; total contacts = 1491) addressing maternal daily
      habits, breastfeeding, and depression. Intervention and control mothers were
      similar in weight, Body Mass Index (BMI), depression and social support at
      baseline and 6 months later. The percentage of low birth weight babies was
      similar; intervention infants' growth (weight/height Z score) tended to be
      significantly better compared to the control condition. DISCUSSION: There are
      many explanations for the failure to find significant benefits: insufficient
      statistical power; the benefits of repeated assessments by warm, supportive peers
      to improve outcomes; or the failure of EBP and the need to maintain replication
      with fidelity. All study mothers had better outcomes than documented among
      comparable published samples of low-income, Latina and Korean-American mothers in
      Los Angeles, CA. ClinicalTrials.gov registration NCT01687634.

PMID- 28755043
TI  - Women's Perspectives of Needs Surrounding Adverse Birth Outcomes: A Qualitative
      Assessment of the Neighborhood Impact of Adverse Birth Outcomes.
AB  - Objectives African Americans are two times more likely to suffer adverse birth
      outcomes (i.e., low birth weight, preterm birth, and infant mortality) when
      compared to all other ethnic groups and this pattern is no different for Douglas
      County, Nebraska, where the majority of African Americans in Nebraska reside. Our
      goal was to identify factors, as described by local women, that contribute to
      adverse birth outcomes in the predominantly African American community of
      Northeast Douglas County in Omaha, NE, to ensure that these women's voices were
      included in the development of interventions to improve their neighborhood's
      birth outcomes. The paper describes the results of a qualitative needs assessment
      of these women which will aid in the design and implementation of neighborhood
      based solutions. Methods We brought together a group of women with varying levels
      of birthing experience, time spent living in the neighborhood, and overall
      community involvement. Individual in-depth, in person, and telephone interviews
      were used to collect participants' perceptions of birth outcomes, neighborhood
      resources for pregnant women, and neighborhood strengths and weaknesses. Results
      The needs assessment identified that, although women in this neighborhood have
      experience with adverse birth outcomes, these experiences are not discussed
      resulting in a lack of awareness of the wide spread racial disparities in birth
      outcomes and the efforts and resources to address this public health problem.
      Conclusions for Practice This study reveals the power of direct conversations
      with women impacted by adverse birth outcomes, as they must be primary partners
      in any efforts to improve birth outcomes.

PMID- 28755044
TI  - Adolescent Reproductive and Contraceptive Knowledge and Attitudes and Adult
      Contraceptive Behavior.
AB  - Objectives Ineffective and inconsistent contraceptive use is common among adults,
      perhaps due to limited knowledge about reproduction and unfavorable attitudes
      toward contraception. Knowledge and attitudes are first developed in adolescence.
      We test whether adolescent knowledge and attitudes have long-term implications
      for adult contraceptive behavior. Methods Using the National Longitudinal Survey
      of Adolescent to Adult Health, our analytical sample (n = 6662) consists of those
      asked sex and contraception questions at Wave I (1995; students aged 15 and
      older) and who were sexually active and not pregnant at the time of the Wave IV
      (2007-2008) survey. We examined whether adolescent attitudes toward
      contraception, knowledge of condoms and reproduction, and confidence in
      contraceptive knowledge were predictive of adult contraceptive efficacy and
      consistency using logistic regression. Results In models adjusted for a range of
      socioeconomic, demographic, and life course factors, favorable attitudes toward
      contraception in adolescence increased the odds (aOR 1.21, CI 1.08-1.36) of using
      more effective methods rather than a less effective or no method of contraception
      in adulthood, as did more accurate condom knowledge (aOR 1.07, CI 1.00-1.14) and
      more accurate reproductive knowledge (aOR 1.07, CI 1.00-1.13). Adolescents with
      more favorable attitudes toward contraception also used contraception more
      consistently as adults (aOR 1.27, CI 1.14-1.43), as did those with more accurate
      condom knowledge (aOR 1.10, CI 1.03-1.18). Conclusions Attitudes towards
      contraception and knowledge about condoms and reproduction acquired during
      adolescence are predictive of adult contraceptive behavior. Results suggest that
      comprehensive sex education during adolescence could improve effective
      contraceptive behavior throughout the life course.

PMID- 28755045
TI  - Influences on Immunization Decision-Making among US Parents of Young Children.
AB  - Objectives This study assessed influences on vaccination decisions among parents
      of young children and examined common vaccination information and advice sources.
      Methods Using panel samples of parents of children under 7 years, web-based
      surveys were conducted in 2012 (n = 2603) and 2014 (n = 2518). A vaccine decision
      making typology (non-hesitant acceptors, hesitant acceptors, delayers, and
      refusers) was established and weighted population estimates of potential factors
      influencing parental vaccination decision (e.g., provider influence, source of
      information and advice) were computed by year and decision type. Results Delayers
      and refusers were more likely than acceptors to know someone whose child
      experienced a severe reaction to a vaccine or delayed/refused vaccine(s). High
      proportions of delayers (2012: 33.4%, 2014: 33.9%) and refusers (2012: 49.6%,
      2014: 58.6%) reported selecting their healthcare provider based on whether the
      provider would allow them to delay/refuse vaccines. Providers were the most
      frequently reported trusted vaccine information source among all parents, though
      more often by acceptors than refusers (2012, 2014: p < 0.01). We found differing
      patterns of provider advice-seeking and internet as a reliable vaccine
      information source by group. Among those who had considered delay/refusal, trust
      in their healthcare provider's advice was the most common reason cited for their
      decision reversal. Conclusions for Practice Provider trust and communication
      along with varying degrees of personal-network influences likely contribute to
      immunization decisions of parents. Vaccine hesitant parents often seek providers
      amenable to accommodating their vaccine beliefs. Providers may benefit from
      vaccine communication training as their recommendations may influence hesitant
      parents to immunize their children.

PMID- 28755046
TI  - Associations Between Peer Counseling and Breastfeeding Initiation and Duration:
      An Analysis of Minnesota Participants in the Special Supplemental Nutrition
      Program for Women, Infants, and Children (WIC).
AB  - Background Peer counseling (PC) has been associated with increased breastfeeding
      initiation and duration, but few analyses have examined the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC) model for peer
      counseling or the continuation of breastfeeding from birth through 12 months
      postpartum. Objectives Identify associations between Minnesota WIC Peer
      Breastfeeding Support Program services and breastfeeding initiation and
      continuation. Methods Retrospective analysis of observational data from the
      Minnesota WIC program's administrative database of women who gave birth in 2012
      and accepted a PC program referral prenatally (n = 2219). Multivariate logistic
      regression and Cox regression models examined associations between peer services
      and breastfeeding initiation and continuation of any breastfeeding. Results Among
      women who accepted referral into a PC program, odds of initiation were
      significantly higher among those who received peer services (Odds Ratio (OR):
      1.66; 95% CI 1.19-2.32), after adjusting for confounders. Women who received peer
      services had a significantly lower hazard of breastfeeding discontinuation from
      birth through 12 months postpartum than women who did not receive services.
      (Hazard Ratio (HR) month one: 0.45; 95% CI 0.33-0.61; months two through twelve:
      0.33; 95% CI 0.18-0.60). The effect of peer counseling did not differ
      significantly by race and ethnicity, taking into account mother's country of
      origin. Conclusion for practice Receipt of peer services was positively
      associated with breastfeeding initiation and continued breastfeeding from birth
      through 12 months postpartum. Making peer services available to more women,
      especially in communities with low initiation and duration, could improve
      maternal and child health in Minnesota.

PMID- 28755047
TI  - Potential Impacts of Modifiable Behavioral and Environmental Exposures on
      Reducing Burden of Under-five Mortality Associated with Household Air Pollution
      in Nepal.
AB  - Objectives Household air pollution (HAP) is one of the leading causes of
      respiratory illness and deaths among young children in low and lower-middle
      income countries. This study examines for the first time trends in the
      association between HAP from cooking fuel and under-five mortality and measures
      the potential impact of interventions to reduce HAP using Nepal Demographic and
      Health Survey datasets (2001-2011). Methods A total of 17,780 living children
      across four age-groups (neonatal 0-28 days, post-neonatal 1-11 months, child 12
      59 months and under-five 0-59 months) were included and multi-level logistic
      regression models were used for analyses. Population attributable fractions of
      key risk factors and potential impact fractions assessing the impact of previous
      interventions to reduce exposure prevalence were also calculated. Results Use of
      cooking fuel was associated with total under-five mortality (OR 2.19, 95% CI 1.37
      3.51, P = 0.001) in Nepal, with stronger associations evident for sub-group
      analyses of neonatal mortality (OR 2.67, 95% CI 1.47-4.82, P = 0.001). Higher
      association was found in rural areas and for households without a separate
      kitchen using polluting fuel for cooking, and in women who had never breastfed
      for all age-groups of children. PIF estimates, assuming a 63% of reduction of HAP
      based on previously published interventions in Nepal, suggested that a burden of
      40% of neonatal and 33% of under-five mortality cases associated with an indoor
      kitchen using polluting fuel could be avoidable. Conclusion Improved
      infrastructure and behavioral interventions could help reduce the pollution from
      cooking fuel in the household resulting in further reduction in under-five
      mortality in Nepal.

PMID- 28755048
TI  - Contraceptive Implant Discontinuation in Huambo and Luanda, Angola: A Qualitative
      Exploration of Motives.
AB  - Introduction The Government of Angola is engaged in ongoing efforts to increase
      access to contraceptives, in particular contraceptive implants (CIs).
      Discontinuation of CIs, however, has been identified as being a challenge to this
      work, hindering the improvement of contraceptive prevalence, and in turn,
      maternal and child health. The objective of this study was to understand motives
      for contraceptive implant discontinuation in Luanda and Huambo, Angola. Methods
      We conducted 45 in-depth interviews and six focus groups amongst former and
      current contraceptive implant clients and family planning nurses in eight clinics
      across the provinces of Huambo and Luanda. Data collectors transcribed and
      translated key information from Portuguese into English. We used a combined
      deductive/inductive approach to code and analyze data. Results Participants
      described adverse side effects, desire for pregnancy, partner dissatisfaction,
      quality of care, alternative or lack of information, and religion as motives for
      discontinuation. Adverse side effects, including prolonged bleeding, amenorrhea,
      and headaches were most commonly cited by both clients and providers. Discussion
      Motives for discontinuation reflect existing findings from other studies in
      similar settings, in particular the influence of adverse side effects and desire
      for pregnancy as motivating factors. We contextualize these findings in the
      Angolan setting to tease out the relationship between cultural norms of ideal
      family size and the perceived role of women in regards to fertility and child
      bearing. We suggest that programs enter into dialog with communities to address
      these concerns, rather than working exclusively on improving service delivery and
      quality.

PMID- 28755049
TI  - Maternal, Newborn, and Child Health After the 2015 Nepal Earthquakes: An
      Investigation of the Long-term Gendered Impacts of Disasters.
AB  - Introduction Natural disasters in resource-poor countries have differential
      effects on socially disadvantaged groups such as women. In addition to the acute
      reproductive health needs of women during the immediate response phase of a
      disaster, research suggests that maternal, newborn, and child health (MNCH) may
      continue to be seriously impacted for numerous months, even years, after the
      event. Methods This ethnographic field research investigates the impacts of the
      2015 Nepal earthquakes on mothers and children under five on the 6-month
      anniversary of the earthquakes. Results Though families were not channeling
      household funds away from health care expenses for pregnant and lactating women
      and children under five, the findings suggest that a delayed response by the
      Nepali government in administering funds for rebuilding combined with an ongoing
      fuel crisis were negatively impacting families' abilities to provide adequate
      shelter, warmth, cooking gas, and transportation for mothers and young children.
      This study highlights the importance of understanding the impacts of specific
      social and political contexts on intra-household family finances as they relate
      to MNCH, not just variables related to the disaster itself. Discussion Future
      research and policies on MNCH during the long-term recovery period after a
      natural disaster such as the 2015 Nepal earthquakes therefore should take into
      account the social and political context as well as institute multiple periodic
      assessments of MNCH in the first few years following the disaster.

PMID- 28755050
TI  - Glutamate Neonatal Excitotoxicity Modifies VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2
      Protein Expression Profiles During Postnatal Development of the Cerebral Cortex
      and Hippocampus of Male Rats.
AB  - Vascular endothelial growth factor (VEGF) exerts both neuroprotective and
      proinflammatory effects in the brain, depending on the VEGF (A-E) and VEGF
      receptor (VEGFR1-3) types involved. Neonatal monosodium glutamate (MSG) treatment
      triggers an excitotoxic degenerative process associated with several
      neuropathological conditions, and VEGF messenger RNA (mRNA) expression is
      increased at postnatal day (PD) 14 in rat hippocampus (Hp) following the
      treatment. The aim of this work was to establish the changes in immunoreactivity
      to VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 proteins induced by neonatal MSG treatment
      (4 g/kg, subcutaneous, at PD1, 3, 5 and 7) in the cerebral motor cortex (CMC) and
      Hp. Samples collected from PD2 to PD60 from control and MSG-treated male Wistar
      rats were assessed by western blotting for each protein. Considering that
      immunoreactivity measured by western blotting is related to the protein
      expression level, we found that each protein in each cerebral region has a
      specific expression profile throughout the studied ages, and all profiles were
      differentially modified by MSG. Specifically, neonatal MSG treatment
      significantly increased the immunoreactivity to the following: (1) VEGF-A at PD8
      PD10 in the CMC and at PD6-PD8 in the Hp; (2) VEGF-B at PD2, PD6 and PD10 in the
      CMC and at PD8-PD9 in the Hp; and (3) VEGFR-2 at PD6-PD8 in the CMC and at PD21
      PD60 in the Hp. Also, MSG significantly reduced the immunoreactivity to the
      following: (1) VEGF-B at PD8-PD9 and PD45-PD60 in the CMC; and (2) VEGFR-1 at PD4
      PD6 and PD14-PD21 in the CMC and at PD4, PD9-PD10 and PD60 in the Hp. Our results
      indicate that VEGF-mediated signalling is involved in the excitotoxic process
      triggered by neonatal MSG treatment and should be further characterized.

PMID- 28755051
TI  - Reference frames in spatial updating when body-based cues are absent.
AB  - The current study investigated the reference frame used in spatial updating when
      idiothetic cues to self-motion were minimized (desktop virtual reality). In
      Experiment 1, participants learned a layout of eight objects from a single
      perspective (learning heading) in a virtual environment. After learning, they
      were placed in the same virtual environment and used a keyboard to navigate to
      two of the learned objects (visible) before pointing to a third object
      (invisible). We manipulated participants' starting orientation (initial heading)
      and final orientation (final heading) before pointing, to examine the reference
      frame used in this task. We found that participants used the initial heading and
      the learning heading to establish reference directions. In Experiment 2, the
      procedure was almost the same as in Experiment 1 except that participants pointed
      to objects relative to an imagined heading that differed from their final heading
      in the virtual environment. In this case, pointing performance was only affected
      by alignment with the learning heading. We concluded that the initial heading
      played an important role in spatial updating without idiothetic cues, but the
      representation established at this heading was transient and affected by the
      interruption of spatial updating; the learning heading, on the other hand,
      corresponded to an enduring representation which was used consistently.

PMID- 28755052
TI  - USP Apparatus 4: a Valuable In Vitro Tool to Enable Formulation Development of
      Long-Acting Parenteral (LAP) Nanosuspension Formulations of Poorly Water-Soluble
      Compounds.
AB  - Long-acting or extended release parenteral dosage forms have attracted extensive
      attention due to their ability to maintain therapeutic drug concentrations over
      long periods of time and reduce administration frequency, thus improving patient
      compliance. It is essential to have an in vitro release (IVR) testing method that
      can be used to assure product quality during routine production as well as
      predict and understand the in vivo performance of a formulation. The purpose of
      this work was to develop a discriminatory in vitro release method to guide
      formulation and process development of long-acting parenteral (LAP)
      nanosuspension formulations composed of poorly water-soluble drugs (BCS class
      II). Injectable nanosuspension formulations were developed to serve as test
      articles for method development. Several different IVR methods were evaluated for
      their application to the formulation screening and process development including
      (1) USP apparatus 2, (2) dialysis and reverse dialysis sac, and (3) continuous
      flow-through cell (USP apparatus 4). Preliminary data shows the promising results
      to support the utilization of USP 4 over more widely accepted USP 2 and dialysis
      methods. A combination of more representative in vivo hydrodynamics and ease of
      maintaining sink conditions yields the USP 4 flow-through cell method a more
      suitable in vitro release method for nanosuspension-based LAP formulations of
      poorly water-soluble compounds, such as compounds A and B.

PMID- 28755053
TI  - Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical
      for Influencing the Design and Selection of Optimal Drug Candidates.
AB  - This commentary reflects the collective view of pharmaceutical scientists from
      four different organizations with extensive experience in the field of drug
      discovery support. Herein, engaging discussion is presented on the current and
      future approaches for the selection of the most optimal and developable drug
      candidates. Over the past two decades, developability assessment programs have
      been implemented with the intention of improving physicochemical and metabolic
      properties. However, the complexity of both new drug targets and non-traditional
      drug candidates provides continuing challenges for developing formulations for
      optimal drug delivery. The need for more enabled technologies to deliver drug
      candidates has necessitated an even more active role for pharmaceutical
      scientists to influence many key molecular parameters during compound
      optimization and selection. This enhanced role begins at the early in vitro
      screening stages, where key learnings regarding the interplay of molecular
      structure and pharmaceutical property relationships can be derived. Performance
      of the drug candidates in formulations intended to support key in vivo studies
      provides important information on chemotype-formulation compatibility
      relationships. Structure modifications to support the selection of the solid form
      are also important to consider, and predictive in silico models are being rapidly
      developed in this area. Ultimately, the role of pharmaceutical scientists in drug
      discovery now extends beyond rapid solubility screening, early form assessment,
      and data delivery. This multidisciplinary role has evolved to include the
      practice of proactively taking part in the molecular design to better align solid
      form and formulation requirements to enhance developability potential.

PMID- 28755054
TI  - MRI features can predict EGFR expression in lower grade gliomas: A voxel-based
      radiomic analysis.
AB  - OBJECTIVE: To identify the magnetic resonance imaging (MRI) features associated
      with epidermal growth factor (EGFR) expression level in lower grade gliomas using
      radiomic analysis. METHODS: 270 lower grade glioma patients with known EGFR
      expression status were randomly assigned into training (n=200) and validation
      (n=70) sets, and were subjected to feature extraction. Using a logistic
      regression model, a signature of MRI features was identified to be predictive of
      the EGFR expression level in lower grade gliomas in the training set, and the
      accuracy of prediction was assessed in the validation set. RESULTS: A signature
      of 41 MRI features achieved accuracies of 82.5% (area under the curve [AUC] =
      0.90) in the training set and 90.0% (AUC = 0.95) in the validation set. This
      radiomic signature consisted of 25 first-order statistics or related wavelet
      features (including range, standard deviation, uniformity, variance), one shape
      and size-based feature (spherical disproportion), and 15 textural features or
      related wavelet features (including sum variance, sum entropy, run percentage).
      CONCLUSIONS: A radiomic signature allowing for the prediction of the EGFR
      expression level in patients with lower grade glioma was identified, suggesting
      that using tumour-derived radiological features for predicting genomic
      information is feasible. KEY POINTS: * EGFR expression status is an important
      biomarker for gliomas. * EGFR in lower grade gliomas could be predicted using
      radiogenomic analysis. * A logistic regression model is an efficient approach for
      analysing radiomic features.

PMID- 28755055
TI  - Structured reports of videofluoroscopic swallowing studies have the potential to
      improve overall report quality compared to free text reports.
AB  - PURPOSE: To compare free text (FTR) and structured reports (SR) of
      videofluoroscopic swallowing studies (VFSS) and evaluate satisfaction of
      referring otolaryngologists and speech therapists. MATERIALS AND METHODS: Both
      standard FTR and SR of 26 patients with VFSS were acquired. A dedicated template
      focusing on oropharyngeal phases was created for SR using online software with
      clickable decision-trees and concomitant generation of semantically structured
      reports. All reports were evaluated regarding overall quality and content,
      information extraction and clinical decision support (10-point Likert scale (0 =
      I completely disagree, 10 = I completely agree)). RESULTS: Two
      otorhinolaryngologists and two speech therapists evaluated FTR and SR. SR
      received better ratings than FTR in all items. SR were perceived to contain more
      details on the swallowing phases (median rating: 10 vs. 5; P < 0.001),
      penetration and aspiration (10 vs. 5; P < 0.001) and facilitated information
      extraction compared to FTR (10 vs. 4; P < 0.001). Overall quality was rated
      significantly higher in SR than FTR (P < 0.001). CONCLUSION: SR of VFSS provide
      more detailed information and facilitate information extraction. SR better assist
      in clinical decision-making, might enhance the quality of the report and, thus,
      are recommended for the evaluation of VFSS. KEY POINTS: * Structured reports on
      videofluoroscopic exams of deglutition lead to improved report quality. *
      Information extraction is facilitated when using structured reports based on
      decision trees. * Template-based reports add more value to clinical decision
      making than free text reports. * Structured reports receive better ratings by
      speech therapists and otolaryngologists. * Structured reports on
      videofluoroscopic exams may improve the comparability between exams.

PMID- 28755056
TI  - High resolution post-mortem MRI of non-fixed in situ foetal brain in the second
      trimester of gestation: Normal foetal brain development.
AB  - PURPOSE: To describe normal foetal brain development with high resolution post
      mortem MRI (PMMRI) of non-fixed foetal brains. METHODS: We retrospectively
      collected PMMRIs of foetuses without intracranial abnormalities and chromosomal
      aberrations studied after a termination of pregnancy due to extracranial
      abnormalities or after a spontaneous intrauterine death. PMMRIs were performed on
      a 3-T scanner without any fixation and without removing the brain from the skull.
      All PMMRIs were evaluated in consensus by two neuroradiologists. RESULTS: Our
      analysis included ten PMMRIs (median gestational age (GA): 21 weeks; range: 17-28
      weeks). At 19 and 20 weeks of GA, the corticospinal tracts are recognisable in
      the medulla oblongata, becoming less visible from 21 weeks. Prior to 20 weeks the
      posterior limb of the internal capsule (PLIC) is more hypointense than
      surrounding deep grey nuclei; starting from 21 weeks the PLIC becomes isointense,
      and is hyperintense at 28 weeks. From 19-22 weeks, the cerebral hemispheres show
      transient layers: marginal zone, cortical plate, subplate, and intermediate,
      subventricular and germinal zones. CONCLUSION: PMMRI of non-fixed in situ foetal
      brains preserves the natural tissue contrast and skull integrity. We assessed
      foetal brain development in a small cohort of foetuses, focusing on 19-22 weeks
      of gestation. KEY POINTS: * Post-mortem magnetic resonance imaging (PMMRI) of non
      fixed head is feasible. * PMMRI of unfixed in situ foetal brains preserves the
      natural tissue contrast. * PMMRI provide a good depiction of the normal foetal
      brain development. * PMMRI of unfixed in situ foetal brains preserves the skull
      integrity. * PMMRI pattern of foetal brain development at early gestational age
      is described.

PMID- 28755057
TI  - Feasibility of superb microvascular imaging to detect high-grade vesicoureteral
      reflux in children with urinary tract infection.
AB  - OBJECTIVE: To evaluate superb microvascular imaging (SMI) for the detection of
      high-grade vesicoureteral reflux (VUR). METHODS: We reviewed the patients with
      urinary tract infection who underwent renal US with SMI and VCUG. The subjects
      were divided into a VUR group, which included 17 patients (20 kidney units, KU)
      with high-grade reflux (grade 4 or 5) on VCUG, and a group without VUR including
      the same numbers of subjects. The direction of urine movement at the distal
      ureter and the renal pelvis was reviewed on SMI. SMI and VCUG results were
      compared. RESULTS: Urinary flow "jets" into the bladder and direction of the flow
      were detectable on all SMI examinations in both groups. In the group with VUR, 20
      KUs had grade 4 (n = 11) or grade 5 (n = 9) reflux (bilateral VUR in 3 patients).
      Among 20 KUs with VUR, 15 (75%) showed a reversed ureteral jet and/or renal
      pelvic swirl sign on SMI. None of the patients in the group without VUR showed
      those findings on SMI. CONCLUSION: SMI enables detection of the direction of
      urinary flow. The presence of a reversed ureteral jet and/or renal pelvic swirl
      sign correlates with high-grade VUR with 75% accuracy. KEY POINTS: * Superb
      microvascular imaging is feasible in children with urinary tract infection. * SMI
      enables detection of the direction of urinary flow. * Presence of reversed flow
      correlates with high-grade vesicoureteral reflux.

PMID- 28755058
TI  - Novel Biologic Agents Targeting Interleukin-23 and Interleukin-17 for Moderate-to
      Severe Psoriasis.
AB  - Psoriasis is a common, chronic inflammatory skin disease and cannot be cured. The
      treatment of moderate-to-severe plaque psoriasis has been revolutionized with the
      development of biologic agents for nearly 20 years. Current studies show that
      interleukin-23 and interleukin-17 play remarkable roles in the pathogenesis of
      psoriasis. Interleukin-23 can sustain the differentiation and maintenance of T
      helper-17 lineage. Interleukin-17 can recruit and stimulate many cells, which
      play important parts in psoriasis through interacting with the interleukin-17
      receptor. Several biologic agents targeting interleukin-23, interleukin-17, or
      their receptors are now in different stages: some are approved or clinical trials
      are in progress. Ustekinumab targets interleukin-23/interleukin-12p40;
      risankizumab, guselkumab, and tildrakizumab target interleukin-23p19; secukinumab
      and ixekizumab target interleukin-17A; and brodalumab targets the interleukin-17
      receptors. All of these agents have good efficacy in treating moderate-to-severe
      psoriasis.

PMID- 28755059
TI  - Nusinersen: The First Option Beyond Supportive Care for Spinal Muscular Atrophy.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder
      characterized by degeneration of spinal motor neurons and poses significant
      adverse outcome in affected population. Survival motor neuron 1 (SMN1) protein
      encoded by SMN1 gene located on 5q13 is critical for survival and functioning of
      motor neurons. Almost identical gene SMN2, present on the same chromosome,
      produces a small truncated protein (SMN2) because of skipping of exon 7 from
      translation due to translation silent C6U substitution in exon 7 of SMN2 pre-mRNA
      transcript. Only 10% of the SMN2 mRNAs produce full length SMN2 protein by
      including exon 7 in healthy individuals. A large deletion or sometimes a point
      mutation in SMN1 gene is responsible for SMA. In this case the number of copies
      of SMN2 genes in an individual determines the severity of disease (the more the
      number of copies the less severe the disease). Nusinersen (ISIS 396443) binds to
      intron splicing silencer-N1 (ISS-N1; a site present ten nucleotides down to the
      junction of exon 7 and intron 7), modulating the splicing of SMN2 pre-mRNA
      transcript to increase the inclusion of exon 7, thereby increasing the production
      of full length SMN2 protein. Major evidence of its efficacy came from a sham
      controlled phase 3 clinical study ENDEAR. The study was stopped early based on
      significantly favorable results in interim analysis and all the patients were
      transitioned to receive nusinersen in an ongoing open-label, phase 3 study,
      SHINE, which will evaluate the long-term efficacy, safety and tolerability of the
      drug. Nusinersen is globally the first drug approved (by the US FDA) for
      treatment of SMA in children and adults.

PMID- 28755060
TI  - Prognostic accuracy of SIRS criteria, qSOFA score and GYM score for 30-day
      mortality in older non-severely dependent infected patients attended in the
      emergency department.
AB  - The aim of this study was to determine the accuracy of systemic inflammatory
      response syndrome (SIRS), quick Sepsis-related Organ Failure Assessment (qSOFA)
      score and GYM score to predict 30-day mortality in older non-severely dependent
      patients attended for an episode of infection in the emergency department (ED).
      We performed an analytical, observational, prospective cohort study including
      patients 75 years of age or older, without severe functional dependence, attended
      for an infectious process in 69 Spanish EDs for 2-day three-seasonal periods.
      Demographic, clinical and analytical data were collected. The primary outcome was
      30-day mortality after the index event. We included 1071 patients, with a mean
      age of 83.6 [standard deviation (SD) 5.6] years; 544 (50.8%) were men. Seventy
      two patients (6.5%) died within 30 days. SIRS criteria >= 2 had a sensitivity of
      65% [95% confidence interval (CI) 53.1-75.9] and a specificity of 49% (95% CI
      46.0-52.3), a qSOFA score >= 2 had a sensitivity of 28% (95% CI 18.2-39.8) and a
      specificity of 94% (95% CI 91.9-95.1), and a GYM score >= 1 had a sensitivity of
      81% (95% CI 69.2-88.6) and a specificity of 45% (95% CI 41.6-47.9). A GYM score
      >= 1 and a qSOFA score >= 2 were the cut-offs with the highest sensitivity (p <
      0.001) and specificity (p < 0.001), respectively. The area under the curve (AUC)
      was 0.73 (95% CI 0.66-0.79; p < 0.001) for the GYM score, 0.69 (95% CI 0.61-0.76;
      p < 0.001) for the qSOFA score and 0.65 (95% CI 0.59-0.72; p < 0.001) for SIRS. A
      GYM score >= 1 may be the most sensitive score and a qSOFA score >= 2 the most
      specific score to predict 30-day mortality in non-severely dependent older
      patients attended for acute infection in EDs.

PMID- 28755061
TI  - A Scoping Review of Behavioral Economic Interventions for Prevention and
      Treatment of Type 2 Diabetes Mellitus.
AB  - PURPOSE OF REVIEW: The purpose of this paper was to review studies of behavioral
      economic interventions (financial incentives, choice architecture modifications,
      or commitment devices) to prevent type 2 diabetes mellitus (T2DM) among at-risk
      patients or improve self-management among patients with T2DM. RECENT FINDINGS: We
      found 15 studies that used varied study designs and outcomes to test behavioral
      economic interventions in clinical, workplace, or health plan settings. Of four
      studies that focused on prevention of T2DM, two found that financial incentives
      increased weight loss and completion of a fasting blood glucose test, and two
      choice architecture modifications had mixed effects in encouraging completion of
      tests to screen for T2DM. Of 11 studies that focused on improving self-management
      of T2DM, four of six tests of financial incentives demonstrated increased
      engagement in recommended care processes or improved biometric measures, and
      three of five tests of choice architecture modifications found improvements in
      self-management behaviors. Though few studies have tested behavioral economic
      interventions for prevention or treatment of T2DM, those that have suggested such
      approaches have the potential to improve patient behaviors and such approaches
      should be tested more broadly.

PMID- 28755062
TI  - How Low Can You Go? Reducing Rates of Hypoglycemia in the Non-critical Care
      Hospital Setting.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss strategies to reduce
      rates of hypoglycemia in the non-critical care setting. RECENT FINDINGS:
      Strategies to reduce hypoglycemia rates should focus on the most common causes of
      iatrogenic hypoglycemia. Creating a standardized insulin order set with built-in
      clinical decision support can help reduce rates of hypoglycemia. Coordination of
      blood glucose monitoring, meal tray delivery, and insulin administration is an
      important and challenging task. Protocols and processes should be in place to
      deal with interruptions in nutrition to minimize risk of hypoglycemia. A glucose
      management page that has all the pertinent information summarized in one page
      allows for active surveillance and quick identification of patients who may be at
      risk of hypoglycemia. Finally, education of prescribers, nurses, food and
      nutrition services, and patients is important so that every member of the
      healthcare team can work together to prevent hypoglycemia. By implementing
      strategies to reduce hypoglycemia, we hope to lower rates of adverse events and
      improve quality of care while also reducing hospital costs. Future research
      should focus on the impact of an overall reduction in hypoglycemia to determine
      whether the expected benefits are achieved.

PMID- 28755063
TI  - Brazilian Experience of the Treatment of Alopecia Universalis with the Novel
      Antirheumatic Therapy Tofacitinib: A Case Series.
AB  - INTRODUCTION: Alopecia universalis is an autoimmune disorder for which there is
      no known effective therapy. Tofacitinib-a novel antirheumatic therapy for
      rheumatoid arthritis-has been shown in some reports to induce sustained hair
      growth in patients with alopecia universalis. CASE SERIES: Here, we review the
      experiences of four different rheumatologists across the country regarding four
      Brazilian patients with alopecia universalis who were treated with tofacitinib .
      Two of these four patients had idiopathic alopecia and the other two had
      rheumatoid arthritis; in each case, the alopecia universalis was apparently
      induced by etanercept. CONCLUSION: Tofacitinib should be considered for the
      treatment of severe alopecia areata, but the optimal dose and duration of therapy
      should be defined in randomized controlled trials.

PMID- 28755064
TI  - Inclusion of diverse populations in genomic research and health services: Genomix
      workshop report.
AB  - Clinical genetic services and genomic research are rapidly developing but,
      historically, those with the greatest need are the least to benefit from these
      advances. This encompasses low-income communities, including those from ethnic
      minority and indigenous backgrounds. The "Genomix" workshop at the European
      Society of Human Genetics (ESHG) 2016 conference offered the opportunity to
      consider possible solutions for these disparities from the experiences of
      researchers and genetic healthcare practitioners working with underserved
      communities in the USA, UK and Australia. Evident from the workshop and
      corresponding literature is that a multi-faceted approach to engaging communities
      is essential. This needs to be complemented by redesigning healthcare systems
      that improves access and raises awareness of the needs of these communities. At a
      more strategic level, institutions involved in funding research, commissioning
      and redesigning genetic health services also need to be adequately represented by
      underserved populations with intrinsic mechanisms to disseminate good practice
      and monitor participation. Further, as genomic medicine is mainstreamed,
      educational programmes developed for clinicians should incorporate approaches to
      alleviate disparities in accessing genetic services and improving study
      participation.

PMID- 28755065
TI  - Comment on: "Assessing Pruritus in Hidradenitis Suppurativa: A Cross-Sectional
      Study".

PMID- 28755066
TI  - Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable
      Immune Deficiency.
AB  - PURPOSE: Common variable immunodeficiency (CVID) is a complex, heterogeneous
      immunodeficiency characterized by hypogammaglobulinemia, recurrent infections,
      and poor antibody response to vaccination. While antibiotics and immunoglobulin
      prophylaxis have significantly reduced infectious complications, non-infectious
      complications of autoimmunity, inflammatory lung disease, enteropathy, and
      malignancy remain of great concern. Previous studies have suggested that CVID
      patients diagnosed in childhood are more severely affected by these complications
      than adults diagnosed later in life. We sought to discern whether the rates of
      various infectious and non-infectious conditions differed between pediatric
      diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older).
      METHODS: Using the United States Immunodeficiency Network (USIDNET) database, we
      performed a retrospective analysis of 457 children and adults with CVID,
      stratified by age at diagnosis. Chi-squared testing was used to compare pediatric
      versus adult groups. RESULTS: After correcting for multiple comparisons, we
      identified few statistically significant differences (p <= 0.0004) between
      pediatric and adult groups. Pediatric-onset CVID patients had more frequent
      diagnoses of otitis media, developmental delay, and failure to thrive compared
      with adult-onset CVID patients. Adult CVID patients were more frequently
      diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of
      autoimmunity, lymphoma, and other malignancies were higher in adults but not to a
      significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte
      subsets did not differ significantly between the two groups. When complications
      of infections and co-morbid conditions were viewed categorically, there were few
      differences between pediatric-onset and adult-onset CVID patients. CONCLUSIONS:
      These results suggest that pediatric CVID is not a distinct phenotype. Major
      features were comparable across the groups. This study underscores the need for
      continued longitudinal study of pediatric and early-onset CVID patients to
      further characterize accrual of features over time.

PMID- 28755067
TI  - Efficacy and Safety of Human Intravenous Immunoglobulin 10% (Panzyga(r)) in
      Patients with Primary Immunodeficiency Diseases: a Two-Stage, Multicenter,
      Prospective, Open-Label Study.
AB  - PURPOSE: To assess the efficacy and safety of panzyga(r) (intravenous
      immunoglobulin 10%) in preventing serious bacterial infections (SBIs) in patients
      with primary immunodeficiency diseases (PIDs), a prospective, open-label,
      multicenter, phase 3 study and an open-label extension study were undertaken.
      METHODS: Initially, the study drug (infusion rate <=0.08 mL/kg/min) was
      administered at intervals of 3 or 4 weeks for 12 months, followed by 3 months of
      panzyga(r) at infusion rates increasing from 0.08 to 0.14 mL/kg/min. The primary
      endpoint in the main study was the rate of SBIs per patient-year on treatment.
      Secondary outcomes included non-serious infections, work/school absence, episodes
      of fever, quality of life, and adverse events (AEs). RESULTS: The main study
      enrolled 51 patients (35% female, mean age 26.8 years), with 21 participating in
      the extension study. The rate of SBIs per patient-year was 0.08 in the total
      population; there were four SBIs in the 4-weekly treatment group (2/30 patients)
      and none in the 3-weekly group (n = 21). Compared with 4-weekly treatment, 3
      weekly treatment was associated with a higher rate of upper respiratory tract
      infections (RTIs), ear infections, and work/school absences, but a lower rate of
      lower RTIs and fever. Treatment was generally well tolerated; no AE led to
      treatment withdrawal or death. CONCLUSIONS: Overall, the use of panzyga(r) in
      patients with antibody-deficient PID was associated with a low rate of AEs and
      was effective in preventing SBIs, exceeding US FDA and European Medicines Agency
      recommendations for efficacy.

PMID- 28755068
TI  - [Intravitreal methotrexate for treatment of uveitic cystoid macular edema].
AB  - We present the case of a patient who had several intravitreal methotrexate
      injections due to a uveitic macular edema and a known steroid response. An
      earlier off-label therapy with avastin had not been successful. After the
      intravitreal methotrexate injections a good resorption of the retinal fluid as
      well as a good intraocular pressure and a good visual acuity could be achieved.
      Visual acuity was limited by pre-existing glaucomatous optic nerve atrophy and a
      central scar in the cornea.

PMID- 28755069
TI  - Erratum to: Sarcopenia, but not visceral fat amount, is a risk factor of
      postoperative complications after major hepatectomy.

PMID- 28755071
TI  - Erratum to: Hepatocellular carcinoma detection: diagnostic performance of a
      simulated abbreviated MRI protocol combining diffusion-weighted and T1-weighted
      imaging at the delayed phase post gadoxetic acid.

PMID- 28755070
TI  - [Still's disease in children and adults].
AB  - Systemic juvenile idiopathic arthritis (sJIA) is characterized by fever,
      arthritis, and other signs of systemic inflammation. Historically, sJIA was named
      Still's disease after George Frederic Still, who first reported patients.
      Individuals who manifest after the 16th birthday are diagnosed with adult onset
      Still's disease (AOSD). The pathophysiology of sJIA and AOSD are incompletely
      understood. Increased activation of inflammasomes and the expression of
      proinflammatory cytokines play a central role. S100 proteins, which can activate
      Toll-like receptors, thus, maintaining positive feedback loops, have also been
      detected at increased levels in sera from sJIA patients. Reduced expression of
      the immune-modulatory cytokine IL-10 may further contribute to immune cell
      activation and the production of proinflammatory molecules. Here, we discuss the
      clinical picture, differential diagnoses, the current pathophysiological
      understanding, and treatment options in sJIA and AOSD.

PMID- 28755072
TI  - Cloverleaf duodenum.

PMID- 28755074
TI  - Paediatric renal transplantation: moving forward in the field.

PMID- 28755073
TI  - Urinary biomarkers of cell cycle arrest are delayed predictors of acute kidney
      injury after pediatric cardiopulmonary bypass.
AB  - BACKGROUND: Several novel biomarkers that predict acute kidney injury (AKI) have
      recently been proposed. We have evaluated the sequential patterns of biomarker
      elevation after pediatric cardiopulmonary bypass (CPB) and determined their
      diagnostic accuracy. METHODS: We measured the ability of neutrophil gelatinase
      associated lipocalin (NGAL), interleukin-18 (IL-18), liver type fatty-acid
      binding protein (L-FABP), kidney injury molecule-1 (KIM-1), tissue inhibitor of
      metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein 7
      (IGFBP7), to predict AKI (>=50% increase in serum creatinine from baseline).
      Areas under the receiver-operator characteristic curves (AUCs) were calculated
      for each biomarker and for various biomarker combinations at multiple time points
      after CPB. RESULTS: Of 150 patients examined, AKI had developed in 50 patients by
      24 h after CPB, with an elevated NGAL concentration first noted at 2 h post-CPB,
      increases in IL-18, L-FABP, and the product of TIMP-2 and IGFBP7 first noted at 6
      h, and an elevated KIM-1 level noted at 12 h. At each time point, urine NGAL
      remained the marker with the highest predictive ability (AUC > 0.9). The addition
      of any other biomarker did not increase the predictive accuracy of NGAL alone at
      2 and 6 h. At 12 h, when compared to NGAL alone, the combination of NGAL, IL-18,
      and TIMP2 improved the AUC for AKI prediction (from 0.938 to 0.973). CONCLUSIONS:
      While urine NGAL remains a superior stand-alone test at the 2 and 6 h time points
      after pediatric CPB, a panel of carefully selected biomarkers may prove optimal
      at later time points.

PMID- 28755075
TI  - Rheumatoid arthritis-associated spinal neuroarthropathy with double-level isthmic
      spondylolisthesis.
AB  - INTRODUCTION: To the best of our knowledge, there has been no report regarding
      rheumatoid arthritis associated with spinal neuroarthropathy and combined double
      level isthmic spondylolisthesis. Here, we report a rare case of spinal
      neuroarthropathy with double-level isthmic spondylolisthesis in a rheumatoid
      arthritis (RA) patient. A 56-year-old female patient under medical treatment for
      RA during the last 13 years presented aggravating radiating pain to her right
      lower extremity and a limping gait developed 4 months ago. The disease activity
      of RA had remained low for a long time. Serial radiographs during last 8-year
      follow-up showed progressive dislocation at L4-L5 and L5-S1 with double-level
      isthmic spondylolisthesis and severe destructive status at the last follow-up.
      The patient underwent decompression and circumferential fusion with sacropelvic
      fixation and acceptable reduction was obtained. CONCLUSION: A RA patient with
      double-level isthmic spondylolisthesis showed a progressive destructive lesion.
      In addition to clinical presentations, the imaging findings were very similar to
      ones of spinal neuroarthropathy. The authors conclude that this Grand Round case
      probably had SNA secondary to RA and that this, combined with two-level isthmic
      spondylolisthesis, resulted in her rapidly progressing destructive lumbar lesion.

PMID- 28755076
TI  - Comparative pharmacokinetics of three phenylpropanoids in rat plasma after oral
      administration of Ramulus Cinnamomi and Ramulus Cinnamomi-Ephedrae Herba herb
      couple extract.
AB  - OBJECTIVE: To investigate the pharmacokinetic characteristics of three
      phenylpropanoids (cinnamic acid, cinnamic alcohol and coumarin) in Ramulus
      Cinnamomi (GZ) and Ramulus Cinnamomi-Ephedrae Herba (MH) herb-couple (GZMH).
      METHODS: Twelve male Sprague-Dawley rats were randomly and equally divided into
      the GZ and GZMH herb-couple groups. Blood samples were collected at 0, 0.08,
      0.25, 0.5, 0.75, 1.5, 3, 4, 6, 8, 12, 24, 36 and 48 h after oral administration.
      The three phenylpropanoids in rat plasma were quantified using an ultra
      performance liquid-chromatography with tandem mass spectrometry (UPLC-MS/MS)
      method for pharmacokinetic study. RESULTS: In GZMH group, the area under the
      curve (AUC), mean retention time (MRT) of cinnamic acid and coumarin were
      increased significantly (P<0.01, respectively), and biological half-life (t1/2z)
      was obviously shorter (P<0.05) compared with the GZ group. There were no
      significant differences in the mean retention time from 0 to infinity (MRT0
      infinity), the peak concentration (Cmax), the time to peak (Tmax) and t1/2z,
      except for AUC and MRT0-t (the mean retention time from 0 to t) of cinnamic
      alcohol in the GZMH group by comparison to the GZ group (P<0.01, respectively).
      The AUC, MRT (both P<0.01) and t1/2z (P<0.05) of coumarin were increased
      significantly, while Cmax, and Tmax were decreased slightly by comparison to the
      GZ group (P>0.05). CONCLUSIONS: There were statistically significant differences
      in some pharmacokinetic parameters of the three compounds between GZ and GZMH
      groups, which meant that MH could affect the absorption and elimination of the
      three compounds.

PMID- 28755077
TI  - Processing of calamine with modern analytical techniques: Processed with
      Huanglian Decoction () and Sanhuang Decoction ().
AB  - OBJECTIVE: To determine the pyrolysis characteristics of calcined and processed
      calamine, qualitatively and quantitatively compare the contents of related
      elements, morphology and functional groups of the pyrolysis products dried at
      different heating temperatures and explore the critical temperature and the
      optimal drying temperature for the process of calamine with Huanglian Decoction
      (HLD, ) and San Huang Decoction (SHD, ). METHODS: Pyrolysis products were
      prepared by programmable and constantly heating the calcined and processed
      calamine to or at different heating temperatures. Thermogravimetry (TG) was used
      to test their pyrolysis characteristics. Fourier transform infrared spectroscopy
      and scanning electron microscopeenergy dispersive spectrometer were used to
      determine their morphology, functional groups and element contents. Page model
      was used to investigate the constant drying kinetics of processed calamine.
      RESULTS: The adding of HLD or SHD to calcined calamine (CC) can slow its weight
      loss in drying pyrolysis process. The temperature ranges where HLD and SHD can
      affect its weight loss were 65-150  degrees C and 74-180  degrees C,
      respectively. The drying temperature was optimized as 90  degrees C. The drying
      kinetic for the processed calamine fits Page model shows good linearity.
      CONCLUSIONS: Conclusions: The critical temperature and the optimal drying
      temperature where HLD and SHD can affect the weight loss rate in the process of
      calamine were explored using the theories and methods of both biophysical
      chemistry and processing of Chinese materia medica. This work provides a good
      example for the study of the process of other Chinese medicines using modern
      analytical techniques.

PMID- 28755078
TI  - Weaker cognitive control abilities of Pi (Spleen) qi-deficient individuals
      supported Chinese medicine diagnosis.
AB  - OBJECTIVE: To investigate whether Pi (Spleen) qi-deficiency affected
      psychological and neural responses in relevance to cognitive control. METHODS: Pi
      qi-deficient and balanced participants were asked to perform the Stroop task, a
      classical cognitive control paradigm. In this paradigm, participants had to judge
      the color of the prompted word. The word's meaning indicated the color (the
      consistent condition) or not (the inconsistent condition), or were unrelated to
      the color (the neutral condition). Electroencephalograph (EEG) was recorded
      during the task. RESULTS: Event-related potential (ERP) results showed that Pi qi
      deficient individuals failed to exhibit a normal Stroop effect as Balanced
      individuals did, such as the accuracy differences between the consistent and the
      inconsistent conditions as well as the N450 effect (P>0.05). Meanwhile, Pi qi
      deficient individuals displayed larger P2 and P3 amplitudes than balanced
      individuals did during performing the cognitive control task (P<0.05).
      CONCLUSION: Pi qi-deficiency had psychological and neural basis at least in
      cognitive control aspect.

PMID- 28755079
TI  - Pancreatic adenocarcinoma with a germline PTEN p.Arg234Gln mutation.
AB  - A minor fraction of pancreatic ductal adenocarcinoma (PDAC) develops in
      association with germline mutations of the genes responsible for inherited cancer
      syndromes. However, the PDAC that has a germline PTEN mutation has not received
      much attention. Genome-wide whole exome sequencing was performed on germline and
      somatic DNA from an 82-year-old woman who had developed a solid pancreatic cancer
      but did not show characteristic findings of PTEN hamartoma tumor syndromes
      (PHTS). Histology of the resected pancreatic tumor showed unique PDAC findings of
      primarily dendriform structures and dense fibrous tissue, accompanied by multiple
      pancreatic intraepithelial neoplasias in the vicinity. The tumor
      immunohistochemistry revealed a loss of PTEN expression and overexpression of
      TP53. Exome sequencing revealed a K-ras mutation (p.Gly12Val). Germline exome
      sequencing revealed a missense mutation of PTEN (p.Arg234Gln), a rare variant
      with a reported association with cancer development but not with other PHTS
      phenotypes. To our knowledge, this is the first report of PDAC associated with a
      germline PTEN mutation, particularly a rare variant (p.Arg234Gln) with cancer
      risks.

PMID- 28755080
TI  - Erratum to: Non-invasive measures of coronary microcirculation: Taking the long
      road to the clinic.
AB  - Reference 12 of the original editorial was cited in error. The correct reference
      is: Mohy-ud-Din H, et al. Quantification of intramyocardial blood volume with
      99mTc-RBC SPECT-CT imaging: A preclinical study. J Nucl Cardiol 2017;1-16.

PMID- 28755081
TI  - Cardiovascular disease in the literature: A selection of recent original research
      papers.

PMID- 28755082
TI  - Importance of patient positioning in left ventricular function assessment.

PMID- 28755083
TI  - Psychodynamic psychotherapies for bulimia nervosa: trend and perspectives.

PMID- 28755084
TI  - Design and evaluation of two multi-pinhole collimators for brain SPECT.
AB  - OBJECTIVE: SPECT is a powerful tool for diagnosing or staging brain diseases such
      as Alzheimer's disease (AD) and Parkinson's disease (PD) but is limited by its
      inferior resolution and sensitivity. At the same time, pinhole SPECT provides
      superior resolution and detection efficiency trade-off as compared to the
      conventional parallel-hole collimator for imaging small field-of-view (FOV),
      which fits for the case of brain imaging. In this study, we propose to develop
      and evaluate two multi-pinhole (MPH) collimator designs to improve the imaging of
      cerebral blood flow and striatum. METHODS: We set the target resolutions to be 12
      and 8 mm, respectively, and the FOV at 200 mm which is large enough to cover the
      whole brain. The constraints for system optimization include maximum and minimum
      detector-to-center-of-FOV (CFOV) distances of 344 and 294 mm, respectively, and
      minimal radius-of-rotation (ROR) of 135 mm to accommodate patients' shoulder.
      According to the targeted FOV, resolutions, and constraints, we determined the
      pinhole number, ROR, focal length, aperture acceptance angle, and aperture
      diameter which maximized the system sensitivity. We then assessed the imaging
      performance of the proposed MPH and standard low-energy high-resolution (LEHR)
      collimators using analytical simulations of a digital NCAT brain phantom with
      99mTc-HMPAO/99mTc-TRODAT-1 distributions; Monte Carlo simulations of a hot-rod
      phantom; and a Defrise phantom using GATE v6.1. Projections were generated over
      360 degrees  and reconstructed using the 3D MPH/LEHR OS-EM methods with up to 720
      updates. The normalized mean square error (NMSE) was calculated over the cerebral
      and striatal regions extracted from the reconstructed images for 99mTc-HMPAO and
      99mTc-TRODAT-1 simulations, respectively, and average normalized standard
      deviation (NSD) based on 20 noise realizations was assessed on selected uniform
      3D regions as the noise index. Visual assessment and image profiles were applied
      to the results of Monte Carlo simulations. RESULTS: The optimized design
      parameters of the MPH collimators were 9 pinholes with 4.7 and 2.8 mm pinhole
      diameter, 73 degrees  acceptance angle, 127 mm focal length, 167 mm ROR for 12 mm
      and 8 mm target resolution, respectively. According to the optimization results,
      the detection efficiencies of the proposed collimators were 270 and 40% more as
      compared to LEHR. The Monte Carlo simulations showed that 7.9 and 6.4 mm rods can
      be discriminated for the MPH collimators with target resolutions of 12 and 8 mm,
      respectively. The eight 12 mm-thick discs of the Defrise phantom can also be
      resolved clearly in the axial plane as demonstrated by the image profiles
      generated with the MPH collimators. CONCLUSION: The two collimator designs
      provide superior image quality as compared to the conventional LEHR, and shows
      potential to improve current brain SPECT imaging based on a conventional SPECT
      scanner.

PMID- 28755085
TI  - Risk Factors for Lymph Node Metastasis in Western Early Gastric Cancer After
      Optimal Surgical Treatment.
AB  - BACKGROUND: Lymph node metastasis (LNM) has a strong influence on the prognosis
      of patients with early gastric cancer (EGC). As minimally invasive treatments are
      considered appropriate for EGC, and lymphadenectomy may be restricted or even
      eliminated in some cases; it is imperative to identify the main risk factors for
      LNM to individualize the therapeutic approach. This study aims to evaluate the
      risk factors for LNM in EGC and to determine the adequacy of the endoscopic
      resection criteria in a western population. METHODS: EGC patients who underwent
      gastrectomy with lymphadenectomy were retrospectively analyzed utilizing a
      prospective database. The clinicopathological variables were assessed to
      determine which factors were associated to LNM. RESULTS: Among 474 enrolled
      patients, 105 had EGC (22.1%). LNM occurred in 13.3% of all EGC (10% T1a; 15.4%
      T1b). Tumor size, venous, lymphatic, and perineural invasions were confirmed as
      independent predictors of LNM by multivariate analysis. Expanded criteria were
      safely adopted only in selected cases, and 13.6% of patients who matched expanded
      indication had LNM. CONCLUSIONS: Tumor size, venous, lymphatic, and perineural
      invasions were associated with LNM and should be considered as surrogate markers
      for surgical treatment of EGC. Expanded criteria for endoscopic resection can be
      safely adopted only in selected cases.

PMID- 28755086
TI  - Racial Disparities After Stoma Construction Exist in Time to Closure After 1 Year
      but Not in Overall Stoma Reversal Rates.
AB  - INTRODUCTION: Conflicting data exist on racial disparities in stoma reversal (SR)
      rates. Our aim was to investigate the role of race in SR rates, and time to
      closure, in a longitudinal, racially diverse database. METHODS: All adult
      patients (>18 years) who received an ileostomy or colostomy from 1999 to 2016 at
      a single institution were identified. Primary outcomes were SR rates and time to
      closure. Failure to reverse and time to closure was modeled using Cox regression.
      Kaplan-Meier survival curves, stratified by race, were generated for time to
      closure and hazard ratios (HRs) calculated. RESULTS: Of 770 patients with stomas,
      65.6% of patients underwent SR; 76.6% were white and 23.4% were black. On
      adjusted analysis, race did not predict overall SR rates or time to closure if
      performed less than 1 year. Instead, significant predictors for failure in SR
      included age, insurance status, end colostomy/ileostomy, and loop colostomy (p <
      0.05). Predictors of delay in time to closure included insurance, end
      colostomy/ileostomy, and loop colostomy (p < 0.05). In patients who underwent
      reversal after 1 year, black race was an independent predictor of time to closure
      (HR 0.21, 95% CI 0.07-0.63, p < 0.05). CONCLUSION: SR rates were equal between
      black and white patients. Disparities in time to closure existed only for black
      patients if reversed more than 1 year after index stoma construction. While
      equitable outcomes were achieved for most patients, further investigation is
      necessary to understand stoma disparities after 1 year.

PMID- 28755087
TI  - Efficacy and Cost of Trap-Bait Combinations for Capturing Rhynchophorus palmarum
      L. (Coleoptera: Curculionidae) in Ornamental Palm Polycultures.
AB  - Ornamental palms are an economically important component of international trade
      yet have recently experienced yield losses in Mexico due to red ring and bud rot
      diseases, which are spread by Rhynchophorus palmarum L. Considering that massive
      capture is a common strategy to control this pest and the cost of commercial
      traps and baits could be inaccessible for small farmers, an inexpensive trap-bait
      combination is desired. In this study, 16 trap-bait combinations for capturing R.
      palmarum were assessed in ornamental palm polycultures over the course of 1 year.
      An expensive yellow bucket trap combined with aggregation pheromone + insecticide
      + banana was compared with inexpensive, handmade trap-bait combinations. A total
      of 4712 weevils were collected in all traps, of which 52.7% were male and 47.3%
      female. The efficacy of the handmade trap made from a colorless polyethylene
      bottle and baited with banana + pineapple + sugarcane + sugarcane molasses was
      similar to that of the yellow bucket trap baited with aggregation pheromone +
      insecticide + banana. These two trap-bait combinations remained effective even
      when the R. palmarum population significantly decreased during the dry, warm
      season. The affordable handmade trap baited with food attractants and without
      insecticides was highly efficient in capturing R. palmarum and therefore
      represents an effective tool for monitoring weevil populations. As ornamental
      crops have recently gained greater economic importance in the studied region, the
      use of a novel and cheap trap-bait combination could offer great benefits to
      producers and form part of the integrated management of R. palmarum.

PMID- 28755088
TI  - Adjuvant endocrine monotherapy for postmenopausal early breast cancer patients
      with hormone-receptor positive: a systemic review and network meta-analysis.
AB  - BACKGROUND: In patients with hormone receptor-positive postmenopausal of early
      stage breast cancer, adjuvant endocrine monotherapies include letrozole,
      anastrozole, exemestane, toremifene and tamoxifen. But the optimum regimen
      remains controversial. METHODS: PubMed, Cochrane Database and ClinicalTrials.gov
      were systematically reviewed of abstract for randomized-controlled trials (RCTs)
      to assess the efficacy of tamoxifen, letrozole, exemestane, anastrozle and
      toremifene for postmenopausal patients with hormone-receptor positive (HR+), who
      have not received prior therapy for early stage breast cancer. The outcomes were
      measured by disease-free survival (DFS) and overall survival (OS). We evaluated
      relative hazard ratios (HRs) for death of different therapies by combination
      hazard ratios for death of included trials. The SUCRA values were used to
      evaluate the rankings of efficacy for these monotherapies. RESULTS: A total of
      fourteen studies including 19,517 patients in our research were absorbed and
      estimated. The superiority of efficacy for DFS were 5-year letrozole and 10-year
      tamoxifen (SUCRA values 0.743/0.657) in all comparisons. A more efficient SUCRA
      values for OS were 5-year Exemestane, 5-year letrozole and 10-year tamoxifen
      (0.756/0.677/0.669). CONCLUSIONS: Clinically important differences exist between
      commonly prescribed different adjuvant endocrine monotherapy regimens for both
      efficacy and acceptability in favor of exemestane and letrozole. 10-year
      tamoxifen for early breast cancer patients is noninferior to 5-year anastrozle,
      and might be the best choice where aromatase inhibitors (AIs) are not easy to
      acquire.

PMID- 28755089
TI  - Managing Mild-to-Moderate Psoriasis in Elderly Patients: Role of Topical
      Treatments.
AB  - The approach to managing mild-to-moderate psoriasis in the elderly (ages >65
      years) should be no different to that in the younger population. Topical agents
      are frequently prescribed for elderly patients as first-line therapy because of
      their localized impact and minimal systemic effects. Although topical therapy
      remains the mainstay treatment of mild-to-moderate psoriasis, the elderly
      population may be at a higher risk of steroid-induced adverse events, including
      atrophy, purpura, telangiectasia, secondary skin infections, rebound phenomenon,
      and tachyphylaxis. In addition, offering photo- and systemic therapy to elderly
      patients with mild-to-moderate psoriasis may pose challenges due to the presence
      of comorbidities, patient adherence, and reduced physical functioning.
      Nonetheless, topical therapy remains first-line therapy for elderly and younger
      patients with mild-to-moderate psoriasis as standalone therapy or in combination
      with oral and biologic agents. Effective use of topical treatments should be
      prioritized to ensure elderly patients can be effectively managed prior to
      advancing to photo- or systemic treatment modalities.

PMID- 28755090
TI  - Investigating the Relationship Between Religiosity and Psychological Distress
      Among Surgical Inpatients: A Pilot Study.
AB  - Psychological distress may hinder recovery following surgery. Studies examining
      the relationship between psychological distress and religiosity in the acute post
      operative setting are lacking. The present study investigated this relationship,
      evaluated protocol design, and explored coping mechanisms. Psychological distress
      of surgical inpatients was assessed using the Hospital Anxiety and Depression
      Scale (HADS) and Rotterdam Symptom Checklist (RSCL). Religiosity was assessed
      using the Santa Clara Strength of Religious Faith Questionnaire. Correlations
      were obtained using Minitab software. Qualitative analysis identified coping
      mechanisms. Of eligible inpatients, 13/54 were recruited. No significant
      correlation was found between religiosity and psychological distress. The RSCL
      had a strong correlation with HADS (R = 0.82, p = 0.001). Assessment of distress
      was >2 min faster using RSCL compared to HADS. Relationships with pets, friends
      or family, and God emerged as the most common coping mechanism. Given study
      limitations, no conclusion was drawn regarding the relationship between
      religiosity and psychological distress. Weaknesses in study protocol were
      identified, and recommendations were outlined to facilitate the definitive study.
      This includes use of RSCL instead of HADS. Further study is warranted to explore
      how to strengthen relationships for inpatients.

PMID- 28755091
TI  - CAR T cells targeting solid tumors: carcinoembryonic antigen (CEA) proves to be a
      safe target.

PMID- 28755092
TI  - Pediatric Dosing of Intravenous Sotalol Based on Body Surface Area in Patients
      with Arrhythmia.
AB  - In a recently published study, we evaluated the efficacy and safety of
      intravenous sotalol in pediatric patients with incessant tachyarrhythmias and we
      have found that intravenous sotalol is effective and safe. Our dosing regimen was
      based on the body weight of the patients. In the US, the recommendation for
      intravenous sotalol dosing in pediatric patients is based on body surface area
      (BSA) while taking into consideration the patients' age. The purpose of this
      paper is to show the correspondence of a body weight-based dosing regimen when
      expressed for BSA as mg/m2. We evaluated the similarity of a body weight-based
      dose to that calculated based on BSA using the US labeling recommendations. Of
      the 83 patients, 5 were newborns (age: 0-30 days), 39 infants and toddlers (age:
      1-24 month), 26 young children (age: >2-6 years), 11 older children (age: 6-12
      years), and 2 adolescents (age: 14 years). Each received a loading dose of 1
      mg/kg intravenous sotalol administered over 10 min followed by a maintenance dose
      of 4.5 mg/kg/day. There was a close correlation between the sotalol loading doses
      calculated based on body weight and BSA across the entire age range (r = 0.977, p
      < 0.001). In most of the age groups, the body weight-based loading doses were
      lower or equal to the BSA-based doses. Only in the adolescents were the body
      weight-based doses higher. The maintenance doses given in our study were
      significantly higher than the BSA-based dose in newborns: 75 +/- 6 versus 53 +/-
      8 mg/m2, p < 0.05; infants/toddlers: 88 +/- 14 versus 77 +/- 7 mg/m2, p < 0.001;
      younger children: 113 +/- 12 versus 85 mg/m2, p < 0.001; older children: 123 +/-
      16 versus 85 mg/m2, p < 0.01; and adolescents 157 +/- 30 versus 85.5 mg/m2.
      Despite the rapid administration of the loading dose and the increased
      maintenance doses, our body weight-based dosing regimen was safe. Only one
      newborn had significant adverse event (AV block) that resolved spontaneously
      after discontinuation of the infusion.

PMID- 28755093
TI  - HER2 and TOP2A Gene Amplification and Protein Expression in Upper Tract
      Urothelial Carcinomas.
AB  - HER2, a potential target for therapy, has been described to be amplified in
      urothelial carcinomas. As the topoisomerase II alpha (TOP2A) gene is located
      close to the HER2 gene on chromosome 17q12-q21, it is frequently either co
      amplified or deleted with HER2 amplification. The purpose of this study was to
      assess the impact HER2 and TOP2A gene amplification as well as protein expression
      on outcomes of upper tract urothelial carcinoma (UTUC). HER2 and TOP2A gene
      amplification and protein expression were assessed in 81 patients with radical
      nephroureterectomy for UTUC. Immunohistochemistry and chromogenic in-situ
      hybridization was performed on formalin-fixed, paraffin-embedded samples. HER2
      protein expression was observed in 27/81 (33%) cases, of which 8 cases exhibited
      amplification of HER2. One of them had an additional polysomy 17, whereas 6/67
      HER2 non-amplified cases revealed a polysomy 17. Coamplification of HER2 and
      TOP2A was found in 4 cases, whereas 3 cases showed only HER2 amplification and 20
      cases only TOP2A amplification. HER2 IHC overexpression was associated with
      higher-grade tumors (p = 0.001), non-organ confined carcinomas (p = 0.017), HER2
      amplification (p < 0.00001) and TOP2A amplification (p = 0.016). HER2
      amplification was association with higher tumor grade (p = 0.001) and lymphnode
      metastasis (p = 0.003). TOP2A IHC positivity was significantly associated with
      higher tumor grade (p = 0.0004), TOP2A amplification (p = 0.0003), polysomy 17 (p
      = 0.035) and HER2 IHC overexpression (p = 0.28), whereas all categories of tumor
      stage and HER2 amplification remained not related. TOP2A amplification was
      significantly more frequent in tumors with higher grade, higher tumor stage,
      polysomy 17 and distant metastasis (p = 0.015; p = 0.042; p = 0.032; p = 0.011),
      respectively. In univariate analyses HER2 IHC positivity, TOP2A amplification,
      and polysomy 17 were associated with poor clinical outcome after surgery. HER2
      IHC overexpression and TOP2A amplification are associated with features of
      biologically aggressive UTUC. Overexpression and/or amplification of HER2 and
      TOP2A could help identify patients who may benefit from targeted therapy.

PMID- 28755094
TI  - Awareness of tuberculosis among patients with newly diagnosed immune
      thrombocytopenia in the endemic area.

PMID- 28755096
TI  - Analysis of the hemostatic potential of modern topical sealants on arterial and
      venous anastomoses: an experimental porcine study.
AB  - One of the widely accepted adjunctive agents in the variety of surgical
      modalities are sealants. Our study aim was to compare four commonly used modern
      sealants in a standardized experimental setting to assess their feasibility, and
      hemostatic efficacy in vascular anastomosis. Forty landrace pigs (weight: 24.7 +/
      3.8 kg) were randomized into the control (n = 8) and four sealant groups;
      TachoSil(r) (n = 8), Tissucol Duo(r) (n = 8), Coseal(r) (n = 8), and FloSeal(r)
      (n = 8). After doing a portal vein end-to-end anastomosis as well as stitches of
      aortic incision, the sealants were applied on anastomotic site. The control group
      was left intact. In portal vein anastomosis, the sealants led to a complete
      hemostasis significantly better than control group. The mean of blood loss was
      also significantly reduced. In successful subgroups, there was a difference in
      the mean-time to reach complete hemostasis ranging from 15 s in Coseal(r) to 76 s
      in FloSeal(r) group (p  < 0.05). In aortotomy experiments, except Tissucol
      Due(r), which had insufficient hemostasis, other sealants led to a complete
      hemostasis. The mean blood loss was significantly reduced in sealants groups as
      well. The four sealants are effective in reducing the suture-hole bleeding in
      portal vein anastomosis. However, the hemostatic potential is heterogeneous among
      sealants. This means that "one-size-fits-all" approach is not appropriate for
      application of sealants in diversity of vascular surgery and it should be based
      on the type and the severity of injury and the structure of tissue. Comparison of
      hemostasis efficacy of four modern sealants (TachoSil(r), Tissucol Duo(r),
      Coseal(r), and FloSeal(r)) in vascular anastomosis in porcine model. The figures
      below show the total blood loss (g) in the control and sealant groups after
      aortotomy (left) and portal vein anastomosis (right). The mean of blood loss
      decreased significantly by the usage of sealants in both experiment groups as
      compared to control group (*: p < 0.05; sealant groups vs. control group). 1. The
      right column shows the mean of blood loss (g) in all experiments in each group.
      2. The middle column presents the subgroup with unsuccessful hemostasis at the
      end of observation time (Tmax = 20 sec. for aortotmy and 300 sec. for portal vein
      anastomosis). 3. The left column shows mean of total blood loss in subgroups with
      successful hemostasis during observation time (20 sec for aortotomy and 300 sec
      for portal vein).

PMID- 28755097
TI  - Provider Experiences with Chronic Care Management (CCM) Services and Fees: A
      Qualitative Research Study.
AB  - BACKGROUND: Support for ongoing care management and coordination between office
      visits for patients with multiple chronic conditions has been inadequate. In
      January 2015, Medicare introduced the Chronic Care Management (CCM) payment
      policy, which reimburses providers for CCM activities for Medicare beneficiaries
      occurring outside of office visits. OBJECTIVE: To explore the experiences,
      facilitators, and challenges of practices providing CCM services, and their
      implications going forward. DESIGN: Semi-structured telephone interviews from
      January to April 2016 with 71 respondents. PARTICIPANTS: Sixty billing and non
      billing providers and practice staff knowledgeable about their practices' CCM
      services, and 11 professional society representatives. KEY RESULTS: Practice
      respondents noted that most patients expressed positive views of CCM services.
      Practice respondents also perceived several patient benefits, including improved
      adherence to treatment, access to care team members, satisfaction, care
      continuity, and care coordination. Facilitators of CCM provision included having
      an in-practice care manager, patient-centered medical home recognition,
      experience developing care plans, patient trust in their provider, and
      supplemental insurance to cover CCM copayments. Most billing practices reported
      few problems obtaining patients' consent for CCM, though providers felt that CMS
      could better facilitate consent by marketing CCM's goals to beneficiaries.
      Barriers reported by professional society representatives and by billing and non
      billing providers included inadequacy of CCM payments to cover upfront
      investments for staffing, workflow modification, and time needed to manage
      complex patients. Other barriers included inadequate infrastructure for health
      information exchange with other providers and limited electronic health record
      capabilities for documenting and updating care plans. Practices owned by hospital
      systems and large medical groups faced greater bureaucracy in implementing CCM
      than did smaller, independent practices. CONCLUSIONS: Improving providers'
      experiences with and uptake of CCM will require addressing several challenges,
      including the upfront investment for CCM set-up and the time required to provide
      CCM to more complex patients.

PMID- 28755098
TI  - Opioids and Substance Abuse: Education or Just Regulation?

PMID- 28755099
TI  - Engaging with Communities to Reduce Diabetes Development.

PMID- 28755095
TI  - Neurological Adverse Effects Attributable to beta-Lactam Antibiotics: A
      Literature Review.
AB  - beta-lactam antibiotics are commonly prescribed antibiotic drugs. To describe the
      clinical characteristics, risk markers and outcomes of beta-lactam antibiotic
      induced neurological adverse effects, we performed a general literature review to
      provide updated clinical data about the most used beta-lactam antibiotics. For
      selected drugs in each class available in France (ticarcillin, piperacillin,
      temocillin, ceftazidime, cefepime, cefpirome, ceftaroline, ceftobiprole,
      ceftolozane, ertapenem and aztreonam), a systematic literature review was
      performed up to April 2016 via an electronic search on PubMed. Articles that
      reported original data, written in French, Spanish, Portuguese or English, with
      available individual data for patients with neurological symptoms (such as
      seizure, disturbed vigilance, confusional state, myoclonia, localising signs,
      and/or hallucinations) after the introduction of a beta-lactam antibiotic were
      included. The neurological adverse effects of piperacillin and ertapenem are
      often described as seizures and hallucinations (>50 and 25% of cases,
      respectively). Antibiotic treatment is often adapted to renal function (>70%),
      and underlying brain abnormalities are seen in one in four to one in three cases.
      By contrast, the neurological adverse drug reactions of ceftazidime and cefepime
      often include abnormal movements but few hallucinations and seizures. These
      reactions are associated with renal insufficiency (>80%) and doses are rarely
      adapted to renal function. Otherwise, it appears that monobactams do not have
      serious neurological adverse drug reactions and that valproic acid and carbapenem
      combinations should be avoided. The onset of disturbed vigilance, myoclonus,
      and/or seizure in a patient taking beta-lactam antibiotics, especially if
      associated with renal insufficiency or underlying brain abnormalities, should
      lead physicians to suspect adverse drug reactions and to consider changes in
      antibacterial therapy.

PMID- 28755100
TI  - Point-of-care ultrasonography in Canadian anesthesiology residency programs: a
      national survey of program directors.
AB  - PURPOSE: Point-of-care ultrasonography (POCUS) is a useful tool with multiple
      perioperative applications relevant to the anesthesiologist. Nevertheless, the
      full scope of POCUS applications has yet to be formally incorporated into
      Canadian anesthesiology training. The purpose of this study was to determine the
      current state of POCUS training in Canadian anesthesiology residency programs.
      METHODS: We conducted a web-based survey of program directors from Royal College
      accredited anesthesiology residency programs across Canada. Respondents were
      asked about POCUS training and assessment strategies at their institution as well
      as perceived barriers to POCUS education. We also elicited program directors'
      views on the importance of various POCUS applications as well as future direction
      of POCUS education within Canadian anesthesiology residency programs. RESULTS:
      Thirteen of 17 (76%) program directors responded to our survey. All respondents'
      residency programs provide some training in POCUS-facilitated vascular access,
      peripheral nerve blocks, neuraxial techniques, and transthoracic
      echocardiography. Nevertheless, training varies significantly for the other POCUS
      applications in our survey. The most frequently quoted teaching method employed
      is informal bedside teaching, followed by structured expert demonstration, hands
      on scanning, and didactic lectures. The most frequently quoted barrier to
      teaching POCUS is the lack of trained staff. The majority of respondents agreed
      that competence in POCUS is important for graduating anesthesiology residents,
      and that POCUS should be incorporated into the National Curriculum for Canadian
      Anesthesiology Residency. CONCLUSION: Point-of-care ultrasonography training
      within Canadian anesthesiology residency programs is highly variable. Given the
      importance of POCUS abilities and their relevance to modern anesthesia practice,
      POCUS training and assessment within Canadian anesthesiology residency programs
      should be formalized.

PMID- 28755101
TI  - A rare association of celiac disease and rectal neuroendocrine tumor.
AB  - Celiac disease (CD) is a chronic immune-mediated enteropathy which is triggered
      by dietary gluten in genetically predisposed individuals. Increased risk of all
      gastrointestinal cancers was found during the first year after diagnosis of CD.
      Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous tumor
      group originating from the diffuse neuroendocrine system. Today, the incidences
      of both GEP-NETs and CD have increased due to the increased availability of
      diagnostic tools and awareness. Association of GEP-NETs with CD is rarely seen.
      Here we aimed to present a case in which we diagnosed CD with concurrent rectal
      NET. Association of CD and rectal NET has not been reported in the literature,
      and we believe that our case report can contribute to the epidemiological data.

PMID- 28755102
TI  - Non-surgical ablative therapies for inoperable benign insulinoma.
AB  - PURPOSE: Benign insulinoma is the most common functioning neuroendocrine tumor of
      the pancreas. The gold-standard therapeutic approach for insulinoma is surgery,
      which allows for tumor removal, histology and immunochemical analyses. If surgery
      is not feasible, minimally invasive ablative procedures performed by
      interventional radiology can lead to partial or complete remission of hormone
      hypersecretion and tumor control in insulinoma patients. METHODS: We performed a
      review of existing literature on non-chemotherapeutic/radioactive ablative
      techniques employed for the treatment of benign, otherwise inoperable, pancreatic
      insulinoma. For this purpose, feasibility, effectiveness and safety of ablative
      treatments for pancreatic insulinoma were reviewed from literature data published
      from 1982 to date. RESULTS: A total of 44 insulinoma cases treated with non
      surgical ablative techniques were desumed, and divided as follows: 7 cases of
      tumor embolization, 26 ethanol ablations, 7 radiofrequency ablations, 2 high
      intensity focused ultrasound ablation, 1 irreversible electroporation and 1
      percutaneous microwave ablation. Most cases involved single insulinoma,
      predominantly located in the pancreas head and body. In the majority of patients,
      ablation was chosen instead of surgery due to severe comorbidities. After an
      average follow-up of 16 months, the overall success rate of non-surgical ablative
      treatments of insulinoma was 84%, the recurrence/persistence rate was 16%, and
      transient adverse events were noted in 23% of cases. Adverse events were usually
      self-limiting and medically manageable. CONCLUSIONS: Non-surgical ablation is a
      feasible, safe and repeatable procedure in patients with pancreatic insulinoma,
      who are not candidate to surgery or refuse it. Partial or complete control of
      symptoms and tumor growth is experienced by the majority of patients.

PMID- 28755103
TI  - The Effect of Weekly Set Volume on Strength Gain: A Meta-Analysis.
AB  - BACKGROUND: Strength training set organisation and its relationship to the
      development of muscular strength have yet to be clearly defined. Current meta
      analytical research suggests that different population groups have distinctive
      muscular adaptations, primarily due to the prescription of the strength training
      set dose. OBJECTIVES: We conducted a meta-analysis with restrictive inclusion
      criteria and examined the potential effects of low (LWS), medium (MWS) or high
      weekly set (HWS) strength training on muscular strength per exercise. Secondly,
      we examined strength gain variations when performing multi-joint or isolation
      exercises, and probed for a potential relationship between weekly set number and
      stage of subjects' training (trained versus untrained). METHODS: Computerised
      searches were performed on PubMed, MEDLINE, SWETSWISE, EMBASE and SPORTDiscusTM
      using the terms 'strength training', 'resistance training', 'single sets',
      'multiple sets' and 'volume'. As of September 2016, 6962 potentially relevant
      studies were identified. After review, nine studies were deemed eligible per pre
      set inclusion criteria. Primary data were pooled using a random-effect model.
      Outcomes for strength gain, strength gain with multi-joint and isolation exercise
      were analysed for main effects. Sensitivity analyses were calculated for several
      subgroups by separating the data set and by calculation of separate analyses for
      each subgroup. Heterogeneity between studies was assessed using the Cochran Q and
      I 2 statistics. RESULTS: Pre- versus post-training strength analysis comprised 61
      treatment groups from nine studies. For combined multi-joint and isolation
      exercises, pre- versus post- training strength gains were greater with HWS
      compared with LWS [mean effect size (ES) 0.18; 95% CI 0.06-0.30; p = 0.003]. The
      mean ES for LWS was 0.82 (95% CI 0.47-1.17). The mean ES for HWS was 1.01 (95% CI
      0.70-1.32). Separate analysis of the effects of pre- versus post-training
      strength for LWS or MWS observed marginally greater strength gains with MWS
      compared with LWS (ES 0.15; 95% CI 0.01-0.30; p = 0.04). The mean ES for LWS was
      0.83 (95% CI 0.53-1.13). The mean ES for MWS was 0.98 (95% CI 0.62-1.34). For
      multi-joint exercises, greater strength gains were observed with HWS compared
      with LWS (ES 0.18; 95% CI 0.01-0.34; p = 0.04). The mean ES for LWS was 0.81 (95%
      CI 0.65-0.97). The mean ES for HWS was 1.00 (95% CI 0.77-1.23). For isolation
      exercises, greater strength gains were observed with HWS compared with LWS (ES
      0.23; 95% CI 0.06-0.40; p = 0.008). The mean ES for LWS was 0.95 (95% CI 0.30
      1.60). The mean ES for HWS was 1.10 (95% CI 0.26-1.94). For multi-joint and
      isolation exercise-specific one repetition maximum (1 RM), marginally greater
      strength gains were observed with HWS compared with LWS (ES 0.14; 95% CI -0.01 to
      0.29; p = 0.06). The mean ES for LWS was 0.80 (95% CI 0.47-1.13). The mean ES for
      HWS was 0.97 (95% CI 0.68-1.26). CONCLUSION: This meta-analysis presents
      additional evidence regarding a graded dose-response relationship between weekly
      sets performed and strength gain. The use of MWS and HWS was more effective than
      LWS, with LWS producing the smallest pre- to post-training strength difference.
      For novice and intermediate male trainees, the findings suggest that LWSs do not
      lead to strength gains compared with MWS or HWS training. For those trainees in
      the middle ground, not a novice and not advanced, the existing data provide a
      relationship between weekly sets and strength gain as set configurations produced
      different pre- to post-training strength increases. For well trained individuals,
      the use of either MWS or HWS may be an appropriate dose to produce strength
      gains.

PMID- 28755105
TI  - Cervical brucellosis mimicking cervical disc herniation.
AB  - Brucellar spondylitis may be difficult to diagnose. Initial plain radiographs of
      the spine may show mild degenerative lesions. Although, magnetic resonance
      imaging of spine is mostly helpful to establish the disease, in some cases, it
      may lead to misdiagnosis. The aim of this report was to present a case of
      brucella infection involving the cervical spine that was falsely diagnosed and
      underwent to surgery for cervical disc herniation. Since the spinal form of
      brucellosis has no specific symptomatology, a patient has symptoms with mimicking
      the cervical hernia, with a history of disabling pain more severe than radicular
      pain, and especially who reside in countries where the disease is endemic, the
      brucella infection should be kept in mind in the differential diagnosis and
      specific diagnostic investigations such as brucella agglutination tests should be
      made before any treatment procedure.

PMID- 28755104
TI  - The effects of intranasal esketamine (84 mg) and oral mirtazapine (30 mg) on on
      road driving performance: a double-blind, placebo-controlled study.
AB  - RATIONALE: The purpose of this study is to evaluate the single dose effect of
      intranasal esketamine (84 mg) compared to placebo on on-road driving performance.
      Mirtazapine (oral, 30 mg) was used as a positive control, as this antidepressant
      drug is known to negatively affect driving performance. METHODS: Twenty-six
      healthy volunteers aged 21 to 60 years were enrolled in this study. In the
      evening, 8 h after treatment administration, participants conducted the
      standardized 100-km on-road driving test. Primary outcome measure was the
      standard deviation of lateral position (SDLP), i.e., the weaving of the car. Mean
      lateral position, mean speed, and standard deviation of speed were secondary
      outcome measures. For SDLP, non-inferiority analyses were conducted, using +2.4
      cm (relative to placebo) as a predefined non-inferiority margin for clinical
      relevant impairment. RESULTS: Twenty-four participants completed the study. No
      significant SDLP difference was found between esketamine and placebo (p =
      0.7638), whereas the SDLP after mirtazapine was significantly higher when
      compared to placebo (p = 0.0001). The upper limit of the two-sided 95% confidence
      interval (CI) of the mean difference between esketamine and placebo was +0.86 cm,
      i.e., <+2.4 cm, thus demonstrating that esketamine was non-inferior to placebo.
      Non-inferiority could not be concluded for mirtazapine (+3.15 cm SDLP relative to
      placebo). No significant differences in mean speed, standard deviation of speed,
      and mean lateral position were observed between the active treatments and
      placebo. CONCLUSIONS: No significant difference in driving performance was
      observed 8 h after administering intranasal esketamine (84 mg) or placebo. In
      contrast, oral mirtazapine (30 mg) significantly impaired on road driving
      performance.

PMID- 28755106
TI  - Slap variant with an absent long head of biceps.
AB  - Congenital absence of the long head of biceps is a rare arthroscopic finding. We
      present a unique case of congenital absence of the long head of biceps tendon in
      the presence of a Superior labrum anterior posterior (SLAP) variant lesion.
      Current theories regarding the aetiology of SLAP lesion consider the long head of
      biceps tendon to either avulse or peel-off the labrum from the glenoid rim. Our
      finding of SLAP variant lesion in the absence of the long head of biceps tendon
      suggests that other processes must play a part in the causation of this injury,
      independent of the long head of biceps.

PMID- 28755107
TI  - A missed injury in multiple trauma patient-is it avoidable?
AB  - We report a case of a 24-year-old male with fractures at multiple levels of both
      femur and tibia. The patient was operated upon and a satisfactory clinical
      outcome was achieved. In spite of a thorough secondary survey, a displaced ankle
      fracture had been missed. The case is reported for the unusual combination of
      fractures and to highlight the importance of undetected injuries. We recommend
      that a tertiary survey should be carried out routinely in all polytrauma patients
      to prevent missed injuries.

PMID- 28755108
TI  - Correlation between pre-injury mobility and ASA score with the mortality
      following femoral neck fracture in elderly.
AB  - A poor pre-injury mobility and high American Society of Anaesthiologist (ASA)
      grading is thought to be associated with a poor survival following surgical
      treatment of femoral neck fracture in the elderly. Hence there are concerns among
      orthopaedic surgeons about surgical treatment in this group of patients. In this
      retrospective study, the pre-injury mobility and ASA scores of 401 patients with
      fractured neck of femur treated by surgery was assessed in relation to mortality
      following surgery within the first 30 days of injury. Following surgery, a
      temporary deterioration in the ASA grading and mobility was noticed. Patients who
      required intensive medical care following surgery had higher mortality rate. The
      mortality was 15% among patients with ASA III and 40% among patients with ASA IV.
      14% of 65 immobile patients, 18% of those mobile with Zimmer frame passed away
      after surgery for femoral neck fracture. 6.1% of ASA I scorers died compared with
      40% of ASA IV scorers; this difference was statistically significant
      (chi2=13.883, df=1, P<0.001). Significant number of patients with ASA-IV (60%)
      and immobile patients (88%) survived following surgery for femoral neck fracture.
      Poor pre-injury mobility and high ASA scoring are associated with higher early
      mortality following surgery for femoral neck fracture, however, this should not
      preclude surgery for patients with poor pre-injury ASA grading and mobility
      sustaining femoral neck fracture, as significant number of our patients survived.

PMID- 28755109
TI  - Osteosarcoma of rib in a seven-year-old child: a case report.
AB  - Primary tumours of ribs are relatively uncommon in adults and are even rarer in
      children. (William in Am Surg June: 338-342, 1972; Eskenasy in Rev Roum Morph
      Embryol Physio 1:35-50, 1985) Osteosarcoma is the most common primary bone
      malignancy in children and young adults. (Whelan in Eur J Can 33(10):1611-1619,
      1997) Very few cases of osteosacoma of the rib have been described in literature.
      We report a 7-year-old girl with primary osteosarcoma of the rib which was
      managed by wide excision followed by adjuvant chemotherapy. She is disease free
      after 12 months of follow-up. We believe our case to be the youngest with primary
      osteosarcoma of the rib. Primary osteosarcoma of the rib should be considered in
      the differential diagnosis in a child with rib swelling. Early diagnosis and
      treatment improves the outcome.

PMID- 28755111
TI  - Technical tip: over the C-arm positioning of the uninjured leg for distal locking
      during femoral nailing.

PMID- 28755110
TI  - Ewing's sarcoma masquerading as chronic osteomyelitis: a case report.
AB  - We report an unusual presentation of Ewing's sarcoma in an adult female who was
      treated for tuberculous chronic osteomyelitis before a diagnosis of Ewing's
      sarcoma was finally made. Emphasis is on the fact that these two conditions can
      masquerade each other with delays in diagnosis and possibility of devastating
      results.

PMID- 28755114
TI  - Metal-on-metal surface hip arthroplasty in patients with abnormal Coxanatomy:
      preliminary results.
AB  - The purpose of this study was to evaluate early to intermediate results of metal
      on-metal (MoM) hip resurfacing arthroplasty in patients with abnormal hip
      anatomy. We evaluated nine MoM hip resurfacing arthroplasty in eight patients
      with abnormal coxanatomy performed at a district general hospital in the UK
      between March 1999 and November 2002. One patient had undergone bilateral
      sequential hip resurfacing procedure. These patients were defined to have
      abnormal coxanatomy by virtue of previous dysplastic disease of hip in three
      cases, previous Legg-Calve-Perthes disease, multiple epiphyseal dysplasia, T cell
      acute lymphoblastic leukaemia, trauma and sepsis in one case each. The mean
      follow-up was 40.8 months. The mean age at primary operation was 35 years (range:
      minimum 21 years; maximum 44 years). There were six male and two female patients.
      There were six right-sided and three left-sided procedures. All patients had
      satisfactory outcomes. There were no deep infections, dislocations, or femoral
      neck fractures. Although this is a short series, MoM resurfaced hips with
      appropriate case selection can yield satisfactory short-term to intermediate-term
      results in the young and active patients with abnormal hip anatomy.

PMID- 28755117
TI  - A giant solitary schwannoma of the arm mimicking cyst hydatid.
AB  - We present a 77-year-old female with a size of 9.5*9*7 cm3 giant schwannoma of
      musculocutaneous nerve volarly located in midarm, which was misdiagnosed as cyst
      hydatid on ultrasonographic and magnetic resonance image examination. There was
      not any neurologic sequele after the operation. In case of the similarity of
      their clinical and radiological findings, schwannoma should be included in the
      differential diagnosis of hydatid cysts especially in endemic countries.

PMID- 28755118
TI  - An unfavourable outcome after periprosthetic fracture following metal-on-metal
      surface hip arthroplasty.
AB  - We report a case of a varus malunited periprosthetic femoral neck fracture
      following metal-on-metal hip resurfacing operation. Failure to closely observe
      and poor compliance in the young and active group of patients may contribute to
      such an unfavourable outcome.

PMID- 28755120
TI  - Primary cemented total hip arthroplasty-an Indian experience.
AB  - We report outcome of 9-year follow-up of 50 Charnley cemented primary
      arthroplasties in 47 patients performed between 1996 and 1999. The minimum follow
      up period was 5 years with a mean of 7 years. All hip joints were thoroughly
      assessed preoperatively to document patients' functional level and Harris hip
      score was calculated. All the patients were disabled because of pain in hip and
      45 (90%) had used walking aids. At follow-up all patients were living. The
      radiographs of all patients were available for the entire follow-up period. Of
      the 50 operated hips, only 2 patients (4%) complained of pain while all the rest
      were free of pain. Postoperatively only 10 (20%) patients used support for
      walking. At follow-up none of the hips were revised. Two patients (4%) had
      dislocation in postoperative period in which reduction was done under anesthesia.
      In one patient (2%) prosthesis and cement was removed because of deep infection.
      In two patients (4%) radiolucent clear zone was seen at bone cement interface on
      acetabular side and three (6%) patients had it on femoral component. None of the
      patients developed deep vein thrombosis or heterotopic bone. In postoperative
      period the Harris hip score was calculated in each case and compared with the
      preoperative score to evaluate the outcome. Significant improvement was found in
      Harris hip score after surgery.

PMID- 28755115
TI  - Ankle arthrodesis using a tibio-calcaneal external fixator.
AB  - The results of open ankle arthrodesis in 23 patients with primary and secondary
      ankle-talar arthritis are presented. All patients were treated with open ankle
      arthrodesis using the Citieffe/CH-N external fixator with pins inserted in the
      tibia and the calcaneus. Union rate was 91% (21 patients) at an average of 13
      weeks (range, 12-16 weeks). Mean follow-up was 6 years. Most of the patients
      (91%) were satisfied with the end results of the operation.

PMID- 28755113
TI  - Knee and ankle function after displaced non-isolated fractures of the tibial
      shaft, a retrospective comparison between plate fixation and intramedullary
      nailing.
AB  - Knee and ankle function after tibial shaft fractures have not been evaluated
      comparing intramedullary nailing (IMN) and plate fixation (PF). In a
      retrospective case review study we evaluated 50 patients with history of closed
      tibial and fibular shaft fracture who have been treated by IMN or PF from 1999 to
      2003. Twenty-five patients in each group evaluated for knee and ankle function
      using Iowa knee score, ankle rating score and VAS for the pain. 18.3+/-4.8 weeks
      after PF (mean follow up 35+/-11.7) and 16.4+/-4.6 weeks after IMN fixation (mean
      follow up 36.8+/-11.3) union has been achieved (P<0.17). The knee score was
      89.4+/-10.4 in IMN group and 95.7+/-6.7 in PF one (P<0.01). The ankle rating
      score was 94.7+/-7.2 in IMN and 96.8+/-6.1 in PF (P<0.28). The nail to knee
      distance (average 14+/-5.2 mm) was significantly correlated to the knees'
      function and pain (r=0.599, P<0.002, r=0.583, P<0.002, respectively). T-test
      reveals that knees' function are significantly inferior with transpatellar
      approach in comparison with parapatellar one (86.1+/-10.6 vs. 95.3+/-7.4,
      P<0.01). Our study discloses that using plate may lead to better knee function,
      while IMN causes higher amount of knee pain with controversial reasons.

PMID- 28755112
TI  - Ilizarov's method: a solution for infected bone loss.
AB  - We report the results of 22 infected nonunions treated by radical resection and
      bone transport technique according to Ilizarov with a minimal follow-up period of
      2 years. This series involves four fractures of the femur diaphysis, ten at
      tibial level, four defects of the knee and four of the upper limb. The mean
      length of the bone defect was 7.7 cm. The mean time from the transport procedure
      to frame removal was 14.5 months. In 15 cases the docking site was reviewed to
      refresh the bone ends at the end of the transport procedure, of which eight had a
      bone graft performed. Five refractures were noticed at the docking site in the
      nonrevised group and one in the other group. Two of them were treated
      conservatively and four with a new external fixator. Consolidation was achieved
      in all but two nonunions at the knee level, which means a succesrate of 91%. The
      infection could be eradicated in all 22 patients. A revision of the docking site
      at the end of the bone transport procedure with or without bone grafting is
      recommended.

PMID- 28755116
TI  - Outcome of primary internal fixation of (type C) distal humerus fractures in the
      elderly.
AB  - The aim of this review is to evaluate the functional results of open reduction
      and internal fixation of AO type C distal humerus fractures in elderly patients.
      Twenty patients were recruited in this study with an average age of 73.5 years.
      AO principles were followed, using dual plating in most and inter-fragmentary
      screws to obtain stable fixation. Mobilisation was commenced on the first post
      operative day. Functional results were 72% good or excellent using the index of
      Broberg and Morrey, and 93% good or excellent using the Mayo elbow performance
      index. The average loss of full extension was 17.3 degrees  (0-30 degrees ) and
      the average flexion was 131 degrees  (90-140 degrees ). Radiologically, all
      fractures were united at review although there was few screw loosening and one
      implant failure at the lateral column but this did not influence the functional
      outcome. In conclusion, open reduction and internal fixation of type C distal
      humerus fractures in elderly patients should continue to be the treatment of
      choice.

PMID- 28755119
TI  - Functional outcome following traumatic spondylolisthesis of the axis.
AB  - We reviewed 36 consecutive patients, 24 males and 12 females, presenting to our
      institution, a tertiary referral spinal trauma centre, over a 6-year period. The
      mean age was 46 (range18-82 years) years. We assessed: (a) the mechanism of
      injury, (b) the mode of treatment, (c) the radiographic classification using the
      Levine and Edwards system and (d) functional outcome using the cervical spine
      outcomes questionnaire (CSOQ) by BenDebba. The commonest mechanism of injury was
      road traffic accidents. There were 14 Type-I, 11 Type-II and 1 Type-IIA
      fractures. Twenty-seven patients were treated with halo-vest immobilisation and
      nine were immobilised in a Minerva jacket. All fractures demonstrated
      radiographic union at a mean of 12 (range 10-16) weeks. There were no
      neurological complications. Upon review, all patients, whether Type-I or Type-II
      demonstrated low CSOQ scores approaching their pre-morbid status. However, Type
      II fractures scored higher in three functional outcome categories when compared
      to Type-I fractures.

PMID- 28755121
TI  - Vasculature deprivation-induced osteonecrosis of rats' femoral heads associated
      with the formation of deep surface depressions.
AB  - An impeded blood flow through the femoral head is incriminated in the
      etiopathogenesis of osteonecrosis of the femoral head. The disorder is either
      primary (idiopathic avascular osteonecrosis) or secondary to one condition or
      another, such as corticosteroid medication, fracture of the neck, coagulation
      defects, physical or thermal damage, storage disorders, alcoholism, and
      infectious, autoimmune as also marrow infiltrating diseases. In the wake of the
      necrosis, several mediators are released in increased amounts, prime among which
      is the vascular endothelial growth factor. The intermediates recruit endothelial
      progenitor cells, macrophages, osteoclasts, fibroblasts, and osteoblasts, which,
      pervading throughout the necrotic areas, initiate the reparative processes. The
      dead, soft, and hard tissular debris is substituted by fibrous - later on by
      hematopoietic-fatty tissue - and bone. The newly formed, appositional and
      intramembranous bone is deficient in its mechanical properties. The ordinary load
      carrying functions suffice to deform these weakened femoral heads so that
      osteoarthritic changes develop. Considering contemporary assumptions of the
      causes of osteonecrosis, oxygenation, revascularization, and core decompression
      are the realistic therapeutic interventions. Necrosis of rats' femoral heads is
      studied as a model of osteonecrosis in both adults and children. In view of
      rodents' lifelong persisting physeal cartilage, vascular deprivation-induced
      osteonecrosis in rats mimics children's Perthes disease. The experimental model,
      which is well suited to test treatment modalities, has been used to investigate
      the effects of exposure to hyperbaric oxygen with and without non-weight bearing,
      medication of enoxaparin, and creation of an intraosseous conduit on the
      remodeling of the avascular necrotic femoral head. Intriguingly, the shape of
      treated rats' femoral heads is disfigured to a greater degree than that of
      untreated animals. This is most likely due to the reduced yield strength and
      elastic modulus as well as the raised strain-to-failure of the recently formed
      bone making up the post-necrotic femoral heads. It follows that expedited
      osteogenesis is, counter intuition, detrimental to maintaining the hemispherical
      shape of the femoral head, and thus to an articulation with congruent load
      bearing surfaces. If this is indeed the case, the remodeling of the necrotic
      femoral head should be delayed, rather than sped up, as the present day paradigm
      would have it. Bearing in mind that the dead osseous structures keep their
      mechanical attributes for quite a while, a slowed down new bone formation would
      favor the gradual replacement of the necrotic by living bone. Therefore,
      management of the adult patients with osteonecrosis and children with Perthes
      disease should focus on a slowly progressive substitution so that the decline of
      the bone's mechanical properties is kept to a minimum. One viable therapeutic
      mode is a medication of inhibitors of the vascular endothelial growth factor.

PMID- 28755125
TI  - Recent Literature.

PMID- 28755124
TI  - Nutcracker fracture of the cuboid: a case report.
AB  - Nutcracker fracture of the cuboid is a rare injury usually caused by forced
      abduction of the forefoot on a fixed hindfoot. We report a case of this fracture
      in a 58-year-old man who was treated on the principle of ligamentotaxis and the
      position being held with Kirchner wires for a period of 5 weeks. He recovered
      without any complications and with good ankle and subtalar movements. At 5 months
      following the injury he had returned to his previous occupation. We think this
      novel way of treating this rare fracture is simple and gave a good result in this
      patient.

PMID- 28755123
TI  - Closure of hip wound, clips or subcuticular sutures: does it make a difference?
AB  - The purpose of this study was to investigate wound healing and complications
      following surgery for fracture neck of femur. Seventy-one patients were
      prospectively divided into two groups, according to the method of skin closure:
      group A had clips; group B had subcuticular vicryl(r) sutures. There were 41
      patients in group A, and 30 patients in group B. There were 13 males and 58
      females with an average age of 84.3 years (range 67-100 years). Thirty-seven
      patients underwent fixation with a dynamic hip screw, while 34 had undergone
      either a hemi or total hip arthroplasty. The wounds were inspected at days 2, 5,
      7, 10 and 14 days, for discharge, redness and infection. There was a
      statistically significantly greater amount of wound discharge (P<0.002) and
      redness (P<0.009) in group A (clips) as compared to group B (vicryl). There were
      three cases of infection; all in patients where clips had been used for skin
      closure. We concluded that subcuticular vicryl sutures were significantly better
      than clips in terms of wound healing as well as cost. Except for some decrease in
      operative time there does not seem to be any advantage in the use of clips for
      wound closure.

PMID- 28755128
TI  - ?

PMID- 28755122
TI  - Simultaneous bilateral fracture of femoral neck in elderly patients: report on
      two cases.
AB  - Bilateral fractures of the femoral neck are very rare. We report two cases of
      elderly patients with simultaneous and bilateral femoral neck fractures.

PMID- 28755127
TI  - 'Bouncy castles' and cervical spine fractures: an under-recognized hazard.
AB  - We have recently treated two adult patients with significant spinal injuries
      after using an inflatable 'bouncy castle'. We highlight the risks associated with
      these devices in the adult age group and review the current literature. We
      conclude that these devices should carry a clear warning to adults that their use
      by above-14 is hazardous.

PMID- 28755126
TI  - Semitendinosus ligamentoplasty of the forearm interosseous membrane in a case of
      Essex-Lopresti syndrome.

PMID- 28755136
TI  - Erratum to: Mayarhynchus karlae n. g., n. sp. (Acanthocephala:
      Neoechinorhynchidae), a parasite of cichlids (Perciformes: Cichlidae) in
      southeastern Mexico, with comments on the paraphyly of Neoechinorhynchus Stiles &
      Hassall, 1905.

PMID- 28755130
TI  - Genetic diversity and structure of elite cotton germplasm (Gossypium hirsutum L.)
      using genome-wide SNP data.
AB  - Cotton (Gossypium spp.) is the most important natural textile fiber crop, and
      Gossypium hirsutum L. is responsible for 90% of the annual cotton crop in the
      world. Information on cotton genetic diversity and population structure is
      essential for new breeding lines. In this study, we analyzed population structure
      and genetic diversity of 288 elite Gossypium hirsutum cultivar accessions
      collected from around the world, and especially from China, using genome-wide
      single nucleotide polymorphisms (SNP) markers. The average polymorphsim
      information content (PIC) was 0.25, indicating a relatively low degree of genetic
      diversity. Population structure analysis revealed extensive admixture and
      identified three subgroups. Phylogenetic analysis supported the subgroups
      identified by STRUCTURE. The results from both population structure and
      phylogenetic analysis were, for the most part, in agreement with pedigree
      information. Analysis of molecular variance revealed a larger amount of variation
      was due to diversity within the groups. Establishment of genetic diversity and
      population structure from this study could be useful for genetic and genomic
      analysis and systematic utilization of the standing genetic variation in upland
      cotton.

PMID- 28755132
TI  - Two-stage treatment in patients with patients with high-energy femoral fractures
      does not lead to an increase in deep infectious complications: a propensity score
      analysis.
AB  - PURPOSE: In patients following severe trauma sometimes the physiological
      condition or soft tissue status may not allow definitive fixation of a femoral
      fracture. In these patients, an external fixator can be placed to temporarily
      stabilise the fracture, after which definitive fixation can be performed in a
      second procedure. The aim of this study was to compare the postoperative wound
      infection and union rates of patients treated with direct intramedullary nailing
      (IMN) and patients treated with the 'two-stage treatment'. METHODS: All patients
      with high-energy femoral fractures treated with IMN between 2000 and 2016 in a
      single Level 1 trauma centre were eligible. Electronic charts were reviewed for
      patient and surgical characteristics; furthermore, the development of
      complications was noted. A propensity score analysis was performed to assess the
      attributed risk of the external fixator on the development of postoperative wound
      infections. RESULTS: A total of 149 patients were included in this study; 93
      underwent direct IMN and 56 underwent the two-stage treatment. Patients who
      underwent two-stage treatment were more severely injured, reflected by lower EMV
      and higher ISS on admission. Patients in the two-stage treatment group had a
      significant higher risk of postoperative wound infections (OR: 4.698, 95% CI:
      1.203-18.339) but not a higher risk on deep postoperative wound infections (OR
      2.345, 95% CI: 0.439-12.540). Union rate did not differ between the two groups
      (94% vs 94% NS). CONCLUSIONS: The two-stage treatment is a safe treatment option
      in patients with a high-energy femoral fracture in terms of postoperative wound
      infections. Union rates are also comparable between the two treatment groups.

PMID- 28755138
TI  - Erratum to: Herpesvirus: an underestimated virus.

PMID- 28755129
TI  - Acid-gastric antisecretory effect of the ethanolic extract from Arctium lappa L.
      root: role of H+, K+-ATPase, Ca2+ influx and the cholinergic pathway.
AB  - BACKGROUND: Arctium lappa L., popularly known as burdock, is a medicinal plant
      used worldwide. The antiulcer and gastric-acid antisecretory effects of ethanolic
      extract from roots of Arctium lappa (EET) were already demonstrated. However, the
      mechanism by which the extract reduces the gastric acid secretion remains
      unclear. Therefore, this study was designed to evaluate the antisecretory mode of
      action of EET. MATERIALS AND METHODS: The effects of EET on H+, K+-ATPase
      activity were verified in vitro, whereas the effects of the extract on
      cholinergic-, histaminergic- or gastrinergic-acid gastric stimulation were
      assessed in vivo on stimulated pylorus ligated rats. Moreover, ex vivo
      contractility studies on gastric muscle strips from rats were also employed.
      RESULTS: The incubation with EET (1000 ug/ml) partially inhibited H+, K+-ATPase
      activity, and the intraduodenal administration of EET (10 mg/kg) decreased the
      volume and acidity of gastric secretion stimulated by bethanechol, histamine, and
      pentagastrin. EET (100-1000 ug/ml) did not alter the gastric relaxation induced
      by histamine but decreased acetylcholine-induced contraction in gastric fundus
      strips. Interestingly, EET also reduced the increase in the gastric muscle tone
      induced by 40 mM KCl depolarizing solution, as well as the maximum contractile
      responses evoked by CaCl2 in Ca2+-free depolarizing solution, without impairing
      the effect of acetylcholine on fundus strips maintained in Ca2+ -free nutritive
      solution. CONCLUSION: Our results reinforce the gastric antisecretory properties
      of preparations obtained from Arctium lappa, and indicate that the mechanisms
      involved in EET antisecretory effects include a moderate reduction of the H+, K+
      ATPase activity associated with inhibitory effects on calcium influx and of
      cholinergic pathways in the stomach muscle.

PMID- 28755137
TI  - Comparative Meta-Analysis of the Efficacy of Once-Daily Fluticasone Furoate 100
      uG Versus Twice-Daily Fluticasone Propionate 250 uG in Adolescents and Adults
      with Persistent Asthma.
AB  - Fluticasone furoate and fluticasone propionate are recommended options for
      prophylactic maintenance treatment of persistent asthma. Using data from two
      previous clinical studies (GSK studies: FFA109685/NCT00603278,
      FFA112059/NCT01159912), this meta-analysis compared change from baseline in
      clinic visit mean trough forced expiratory volume in 1 s (FEV1) with fluticasone
      furoate 100 ug once-daily (FF100) versus fluticasone propionate 250 ug twice
      daily (FP250) in adolescents and adults with persistent asthma. Using a
      DerSimonian-Laird random-effects model (primary meta-analysis), there was no
      statistically significant difference between FF100 and FP250 in change from
      baseline in trough FEV1 (-1.7 mL [95% CI -80.4, +77.0], p = 0.9664) and FF100 was
      non-inferior to FP250. Supporting analyses using least squares mean and fixed
      effects model approaches produced similar findings. In this analysis, FF100 and
      FP250 demonstrated a comparable treatment effect on trough FEV1 in patients aged
      >=12 years with persistent asthma; however, results interpretation should
      consider study design and methodological limitations.

PMID- 28755134
TI  - Oscillations in epidemic models with spread of awareness.
AB  - We study ODE models of epidemic spreading with a preventive behavioral response
      that is triggered by awareness of the infection. Previous studies of such models
      have mostly focused on the impact of the response on the initial growth of an
      outbreak and the existence and location of endemic equilibria. Here we study the
      question whether this type of response is sufficient to prevent future flare-ups
      from low endemic levels if awareness is assumed to decay over time. In the ODE
      context, such flare-ups would translate into sustained oscillations with
      significant amplitudes. Our results show that such oscillations are ruled out in
      Susceptible-Aware-Infectious-Susceptible models with a single compartment of
      aware hosts, but can occur if we consider two distinct compartments of aware
      hosts who differ in their willingness to alert other susceptible hosts.

PMID- 28755139
TI  - Within-session reversal learning in rhesus macaques (Macaca mulatta).
AB  - In a midsession reversal (MSR) task, animals are typically presented with a
      simple, simultaneous discrimination (S1+, S2-) where contingencies are reversed
      (S1-, S2+) half-way through each session. This paradigm creates multiple,
      relevant cues that can aid in maximizing overall reinforcement. Recent research
      has shown that pigeons show systematic anticipatory and perseverative errors
      across the session, which increase as a function of proximity to the reversal
      trial. This behavior has been theorized to indicate primary control by temporal
      cues across the session, instead of the cues provided by recent reinforcement
      history that appear to control behavior shown by humans. Rats, however, appear to
      be guided by recent reinforcement history when tested in an operant context,
      thereby demonstrating behavior that parallels that seen in humans, but they
      appear to be guided by temporal cues when tested in an open-field apparatus,
      showing behavior more akin to that seen in pigeons. We tested rhesus macaques
      (Macaca mulatta) on the MSR with a computerized simultaneous visual
      discrimination to assess whether they would show errors indicative of control by
      time or by recent reinforcement history. When a single reversal point occurred
      midsession, rhesus macaques showed no anticipation of the reversal and a similar
      level of perseveration to rats tested in an operant setting. Nearly identical
      results also were observed when the monkeys were trained with a single, variable
      reversal point or with multiple, variable reversal points within a session. These
      results indicate that temporal cues are not guiding response flexibility in
      rhesus macaque visual discrimination.

PMID- 28755131
TI  - Increase in echo intensity and extracellular-to-intracellular water ratio is
      independently associated with muscle weakness in elderly women.
AB  - PURPOSE: The changes in muscle composition and its heterogeneity during aging are
      associated with muscle weakness in elderly persons independent of decreases in
      muscle mass or muscle thickness (MT). Both the assessment of echo intensity (EI)
      with ultrasound imaging and the evaluation of the extracellular
      water/intracellular water (ECW/ICW) ratio with segmental bioelectrical impedance
      spectroscopy (BIS) are non-invasive and convenient methods and seem valuable for
      muscle quality determination. However, no previous study has evaluated both EI
      and the ECW/ICW ratio simultaneously to investigate their relationship to muscle
      strength. The purpose of the present study was to investigate whether both EI and
      the ECW/ICW ratio are independently associated with muscle strength in elderly
      women. METHODS: A total of 179 elderly women with a mean age of 74.1 +/- 4.9
      years, living independently in the community, were enrolled. The MT and EI of the
      quadriceps femoris were measured using transverse ultrasound imaging. The ECW/ICW
      ratio in the upper thigh was calculated from segmental BIS. The maximum knee
      extensor strength and the presence of knee pain were also assessed. RESULTS: Knee
      extensor strength showed a significant positive correlation with MT, and
      significant negative correlations with EI, the ECW/ICW ratio, and age. Stepwise
      regression analysis revealed that knee extensor strength in elderly women was
      predicted by MT, EI, and the ECW/ICW ratio. CONCLUSIONS: This study suggests that
      the simultaneous application of EI and the ECW/ICW ratio is useful in assessing
      muscle strength, and accurately estimates the changes in muscle quality related
      to muscle weakness.

PMID- 28755133
TI  - Training for Direct Support Staff at Group Homes for People with Chronic Mental
      Illness.
AB  - For people with chronic mental illness, their support system (including direct
      support staff at group homes) play a key role in ameliorating exacerbations
      leading to crisis care. However, little information exists on curriculum or
      training programs focused on reducing exacerbations while promoting compassionate
      care. We developed, implemented and evaluated such a program that featured role
      playing and animated videos supplemented with limited didactics. During
      development phase, direct support staff reviewed videos and rated them as
      depicting realistic situations with high acceptability. During implementation,
      the 6-week course (at least one staff from six different group homes not involved
      in the development phase) using a 3-month pre-post design found reductions in
      total number of incident reports and pre-specified outcomes of recipient right
      complaints, emergency calls, and psychiatric hospitalizations. The program
      demonstrated acceptability, improved care and better outcomes on some but not all
      outcomes. Improved training of direct support staff is possible and has positive
      outcomes.

PMID- 28755135
TI  - Macrophage-derived HMGB1 as a Pain Mediator in the Early Stage of Acute
      Pancreatitis in Mice: Targeting RAGE and CXCL12/CXCR4 Axis.
AB  - Extracellular high mobility group box 1 (HMGB1) activates the receptor for
      advanced glycation end products (RAGE) or Toll-like receptor 4 (TLR4) and forms a
      heterocomplex with CXCL12 that strongly activates CXCR4, promoting inflammatory
      and pain signals. In the present study, we investigated the role of HMGB1 in
      pancreatic pain accompanying cerulein-induced acute pancreatitis in mice.
      Abdominal referred hyperalgesia accompanying acute pancreatitis occurred within 1
      h after 6 hourly injections of cerulein. The anti-HMGB1 neutralizing antibody or
      recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1,
      abolished the cerulein-induced referred hyperalgesia, but not pancreatitis
      itself. Plasma or pancreatic HMGB1 levels did not change, but macrophage
      infiltration into the pancreas occurred 1 h after cerulein treatment.
      Minocycline, a macrophage/microglia inhibitor, ethyl pyruvate that inhibits HMGB1
      release from macrophages, or liposomal clodronate that depletes macrophages
      prevented the referred hyperalgesia, but not pancreatitis. Antagonists of RAGE or
      CXCR4, but not TLR4, strongly suppressed the cerulein-induced referred
      hyperalgesia, but not pancreatitis. Upregulation of RAGE, CXCR4 and CXCL12, but
      not TLR4, were detected in the pancreas 1 h after cerulein treatment. Our data
      suggest that HMGB1 regionally secreted by macrophages mediates pancreatic pain by
      targeting RAGE and CXCL12/CXCR4 axis in the early stage of acute pancreatitis.

PMID- 28755140
TI  - Circulating levels of PTEN and KLLN in papillary thyroid carcinoma: can they be
      considered as novel diagnostic biomarkers?
AB  - PURPOSE: PTEN and KLLN are two tumor suppressor genes located in 10q23, share a
      bidirectional promoter and have roles in carcinogenesis. Formerly, the role of
      PTEN mutations and KLLN epimutations were identified in incidence of thyroid
      lesions in individuals with Cowden syndrome, a rare autosomal dominant inherited
      disorder. This study is the first of its type to assess PTEN and KLLN circulating
      levels in patients with sporadic papillary thyroid carcinoma (PTC) and compare to
      patients with multinodular goiter (MNG) and healthy individuals. METHODS: Plasma
      levels of PTEN and KLLN were determined by enzyme-linked immunosorbent assay in
      three groups consisted of PTC (n = 33), MNG (n = 26) and healthy persons (n =
      30). The association of demographic/pathological characteristics with the levels
      of PTEN and KLLN were evaluated. RESULTS: A significant lower plasma levels of
      PTEN and KLLN were observed in PTC patients compared with those of healthy
      persons (PTEN, 9.43 +/- 3.20 vs. 16.96 +/- 1.28 ng/ml, P = 0.000; KLLN, 1.81 +/-
      0.83 vs. 2.57 +/- 1.09 ng/ml, P = 0.005), while no statistical difference was
      found between PTC and MNG groups. Patients with MNG lesion had significantly
      lower levels of PTEN/KLLN (PTEN, 9.62 +/- 2.97 vs. 16.96 +/- 1.28 ng/ml, P =
      0.000; KLLN, 1.34 +/- 0.86 vs. 2.57 +/- 1.09 ng/ml, P = 0.000) compared to the
      healthy controls. The demographic/pathological characteristics did not
      demonstrate an association with the levels of PTEN and KLLN. CONCLUSIONS: The
      study suggests that the lowered levels of PTEN and KLLN are associated with both
      sporadic PTC and MNG tumorigenesis, but they cannot be considered as circulating
      biomarkers for differential diagnosis between malignancy and benignity in
      indeterminate thyroid nodules.

PMID- 28755141
TI  - Locoregional Recurrence Following Breast Cancer Surgery in the Trastuzumab Era: A
      Systematic Review by Subtype.
AB  - INTRODUCTION: Increasing evidence suggests that molecular subtype influences
      locoregional recurrence (LRR) of breast cancer. Previous systematic reviews that
      evaluated the quantitative influence of subtype on LRR predated the use of
      Trastuzumab. This study assessed the impact of subtype on LRR in a contemporary
      treatment era. METHODS: A comprehensive search for all published studies
      assessing LRR according to breast cancer subtype was performed. Only studies with
      patients treated with Trastuzumab were included. Relevant data were extracted
      from each study for systematic review. Primary outcome was LRR related to breast
      cancer subtype. RESULTS: In total, 11,219 patients were identified from seven
      studies. Overall LRR rate was 3.44%. The lowest LRR rates were in luminal A
      (1.7%), and the highest rates were in triple-negative (7.4%) subtypes. There were
      significantly lower risks of LRR in patients with luminal A subtype compared with
      luminal B [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.38-0.76; p <
      0.0004], HER2/neu-overexpressing (OR 0.32, 95% CI 0.24-0.45; p < 0.0001) and
      triple-negative breast cancers (OR 0.25, 95% CI 0.19-0.32; p < 0.0001). There
      were significant differences in LRR between the luminal B and HER2/neu
      overexpressing breast cancers (OR 0.61, 95% CI 0.41-0.89; p = 0.0145). The
      reduced risk in HER2/neu overexpressing compared with triple-negative breast
      cancers approached statistical significance (OR 0.75, 95% CI 0.55-1.03; p =
      0.0933). CONCLUSIONS: Significant variations in LRR occur across breast cancer
      subtypes, with lowest rates in luminal cancers and highest rates in triple
      negative breast cancers. Low levels of LRR highlight advances in breast cancer
      management in the contemporary era.

PMID- 28755142
TI  - Erratum to: White matter measures are near normal in controlled HIV infection
      except in those with cognitive impairment and longer HIV duration.

PMID- 28755143
TI  - Relational autonomy in informed consent (RAIC) as an ethics of care approach to
      the concept of informed consent.
AB  - The perspectives of the dominant Western ethical theories, have dominated the
      concepts of autonomy and informed consent for many years. Recently this dominant
      understanding has been challenged by ethics of care which, although, also
      emanates from the West presents a more nuanced concept: relational autonomy,
      which is more faithful to our human experience. By paying particular attention to
      relational autonomy, particularity and Process approach to ethical deliberations
      in ethics of care, this paper seeks to construct a concept of informed consent
      from the perspective of ethics of care which is here called relational autonomy
      in-informed consent (RAIC). Thus, providing a broader theoretical basis for
      informed consent beyond the usual theoretical perspectives that are particularly
      Western. Care ethics provides such a broader basis because it appeals to a global
      perspective that encompasses lessons from other cultures, and this will help to
      enrich the current ideas of bioethics principles of autonomy and informed
      consent. This objective will be achieved by exploring the ethics of care emphasis
      on relationships based on a universal experience of caring; and by contrasting
      its concept of autonomy as relational with the understanding of autonomy in the
      approaches of the dominant moral theories that reflect rational, individualistic,
      and rights-oriented autonomy of the American liberalism.

PMID- 28755144
TI  - Cadmium, mercury, and nickel adsorption by tetravalent manganese feroxyhyte:
      selectivity, kinetic modeling, and thermodynamic study.
AB  - This study is aiming to investigate tetravalent manganese feroxyhyte (TMFx)
      adsorption efficiency in removing heavy metals. The motivation of this study was
      the fact that TMFx is a highly negatively charged nanostructure material and that
      the metals Cd, Hg, and Ni were characterized as priority pollutants for drinking
      water. TMFx was evaluated through batch and continuous flow experiments in
      National Sanitation Foundation (NSF) water matrix which simulated the
      physicochemical characteristics of natural water. Water's pH significantly
      influences Cd and Ni adsorption efficiency which gradually increases when pH
      value rises from 5 to 9, while the corresponding one for Hg remains almost
      constant. Thermodynamic data showed a spontaneous and an exothermic nature weak
      chemisorption (DeltaEta degrees  = -17.5 +/- 2 kJ/mol) of Cd, Ni, and Hg by TMFx.
      The determined ranking of adsorption affinity and selectivity (Cd > Ni > Hg)
      seems to be governed by the metals' speciation, as well as by hydration free
      energy, which is influenced, however, by their atomic radius. The lower
      adsorption capacity and selectivity of TMFx for Hg should be attributed both to
      uncharged species and to higher atomic radius. The similar Cd and Ni speciation
      in the NSF water matrix leads to the conclusion that the better affinity,
      selectivity, and adsorption kinetic of Cd versus Ni should be attributed to the
      lower hydration free energy of Cd which is in turn related to its higher atomic
      radius. The faster adsorption kinetic (Hg > Cd > Ni) of Hg may be attributed to
      the lower radius of its anhydrate species. Furthermore, TMFx showed high removal
      efficiency under continuous flow application in an adsorption bed setup. The
      determined uptake capacity (q RL) at equilibrium-breakthrough concentration equal
      to the drinking water regulation limit (RL) of each metal were q 1 = 2.5 MUg
      Hg/mg TMFx, q 5 = 5.2 MUg Cd/mg TMFx, and q 20 = 7.1 MUg Ni/mg TMFx. Leaching
      tests of spent TMFx samples from the rapid small-scale column tests (RSSCTs)
      could be treated either as inert wastes after Cd and Ni adsorption or as non
      hazardous waste after Hg adsorption.

PMID- 28755145
TI  - Mosquito control with green nanopesticides: towards the One Health approach? A
      review of non-target effects.
AB  - The rapid spread of highly aggressive arboviruses, parasites, and bacteria along
      with the development of resistance in the pathogens and parasites, as well as in
      their arthropod vectors, represents a huge challenge in modern parasitology and
      tropical medicine. Eco-friendly vector control programs are crucial to fight,
      besides malaria, the spread of dengue, West Nile, chikungunya, and Zika virus, as
      well as other arboviruses such as St. Louis encephalitis and Japanese
      encephalitis. However, research efforts on the control of mosquito vectors are
      experiencing a serious lack of eco-friendly and highly effective pesticides, as
      well as the limited success of most biocontrol tools currently applied. Most
      importantly, a cooperative interface between the two disciplines is still
      lacking. To face this challenge, we have reviewed a wide number of promising
      results in the field of green-fabricated pesticides tested against mosquito
      vectors, outlining several examples of synergy with classic biological control
      tools. The non-target effects of green-fabricated nanopesticides, including acute
      toxicity, genotoxicity, and impact on behavioral traits of mosquito predators,
      have been critically discussed. In the final section, we have identified several
      key challenges at the interface between "green" nanotechnology and classic
      biological control, which deserve further research attention.

PMID- 28755146
TI  - Interaction of different forms of graphene with chicken embryo red blood cells.
AB  - With the rapid development of graphene synthesis and functionalization
      approaches, graphene and its related derivatives have shown great potential in
      many applications in material science, including biomedical applications. Several
      in vitro and in vivo studies clearly showed no definitive risks, while others
      have indicated that graphene might become health hazards. In this study, we
      explore the biocompatibility of graphene-related materials with chicken embryo
      red blood cells (RBC). The hemolysis assay was employed to evaluate the in vitro
      blood compatibility of reduced graphene, graphene oxide, and reduced graphene
      oxide, because these materials have recently been used for biomedical
      applications, including injectable graphene-related particles. This study
      investigated structural damage, ROS production and hemolysis of chicken embryo
      red blood cells. Different forms of graphene, when incubated with chicken embryo
      RBC, were harmful to cell structure and induced hemolysis.

PMID- 28755147
TI  - Meta-analysis of tumour burden in pre-operative axillary ultrasound positive and
      negative breast cancer patients.
AB  - BACKGROUND: Management of the axilla in breast cancer is becoming increasingly
      conservative. Patients identified with a low axillary nodal burden (two or fewer
      involved nodes) at sentinel node biopsy (SNB) can avoid completion axillary node
      clearance (cANC). 'Fast track' to ANC in patients with involved nodes on pre
      operative ultrasound may be over-treating a subgroup of these patients with low
      nodal burden, which would have precluded their need for ANC. This systematic
      review assesses the proportion of patients with involved nodes on pre-operative
      axillary ultrasound, which would fit low axillary burden criteria. METHODS: Meta
      analysis of studies comparing axillary burden of breast cancer patients
      identified as pre-operative ultrasound negative versus positive was performed.
      The primary outcome measure was the number of patients with two or fewer involved
      nodes (macrometastases only). Pooled odds ratio (OR), 95% confidence intervals
      (CIs), means and probabilities of identifying two or fewer involved nodes versus
      greater than two were calculated. RESULTS: Six studies reported the axillary
      burden in 4271 patients who were either directed straight to ANC or cANC after
      SNB. There was a significantly greater axillary burden in the ultrasound positive
      versus negative groups (OR 5.95, 95% CI 5.80-6.11) with mean nodal retrieval
      values of 2.9 [standard error (SE) 0.2] and 1.6 (SE 0.2) nodes, respectively.
      Cumulative probabilities identified 78.9% of ultrasound negative and 43.2% of
      ultrasound positive patients possessed low axillary burden. CONCLUSIONS: Pre
      operative ultrasound positive patients have significantly higher axillary burden.
      However, nearly half do fit the criteria of low axillary burden and could be
      considered for omission of ANC.

PMID- 28755148
TI  - Amplification and overexpression of PSCA at 8q24 in invasive micropapillary
      carcinoma of breast.
AB  - PURPOSE: Invasive micropapillary carcinoma (IMPC) of the breast has distinct
      histological features and molecular genetic profiles. Gains/amplifications of
      8q24 are found associated with IMPC. Although the prostate stem cell antigen
      (PSCA) gene is located at chromosome 8q24, and found over-expressed in prior
      studies, its prognostic values and biological significance in IMPC have not been
      well studied. METHODS: Fluorescence in situ hybridization (FISH) was used to
      assess the frequencies of PSCA copy number gains in IMPC, invasive ductal
      carcinoma of no special type (IDC-NST), and invasive lobular carcinoma (ILC)
      samples. The protein expression levels of PSCA were examined in 56 IMPC, 72 IDC
      NST, and 56 ILC samples using immunohistochemical analysis. RESULTS: PSCA gene
      amplification was detected in 45.2% (14/31) of the IMPC, 28.1% (9/32) of the IDC
      NST, and none (0/25) of the ILC. PSCA protein expression was observed in 58.9%
      (33/56), 40.3% (29/72), and 3.6% (2/56) of IMPC, IDC-NST, and ILC samples,
      respectively. The concordant rate of the immunohistochemistry and FISH data was
      85.2%. PSCA gene amplification highly correlated with its protein overexpression
      (rs = 0.687, P < 0.001), suggesting that gene amplification is an important
      mechanism involved in PSCA overexpression. Our univariate analysis showed that
      the patients with PSCA-positive IMPC had a decreased disease-free survival (DFS)
      compared to PSCA-negative IMPC patients (P = 0.003). Our multivariate analysis
      confirmed the worse DFS in PSCA-positive IMPC patients (P = 0.022). CONCLUSIONS:
      Our results indicate that PSCA may be an attractive target in the 8q24 amplicon
      and that it may serve as a molecular marker of metastasis and recurrence in IMPC.
      The differential expression of PSCA may be associated with cell adhesion.
      Detection of PSCA protein and gene amplification may help manage and predict the
      prognosis of IMPC patients.

PMID- 28755149
TI  - Improving Quality and Decreasing Cost by Reducing Re-admissions in Patients
      Undergoing Total Joint Arthroplasty.
AB  - PURPOSE OF REVIEW: Total joint arthroplasty (TJA) has had an increased demand
      over the recent years. It is a successful procedure, and there are relatively few
      complications, but there is a high overall cost. There is a push to increase the
      quality of care, lessen complications, and decrease cost by reducing
      readmissions. This article will discuss the risk factors that can contribute to
      the complication and readmission rates following TJA. RECENT FINDINGS: Several
      risk factors have been found to contribute to the complication and readmission
      rates following a TJA. It is important to understand these risk factors and
      mitigate them as much as possible in order to optimize the patient experience.
      There are risk factors that cannot be modified, and the treatment team as well as
      the patient should be made aware of these and account for them when making the
      decision whether to undergo elective primary TJA or not. In general, an increased
      number of risk factors is associated with increased complications and increased
      readmission rates. At our institution, we have used this knowledge to improve our
      outcomes and decrease costs. It is important to be mindful of risk factors for
      poor outcomes prior to performing TJA. This allows for the optimization of
      patients prior to undergoing surgery. This can lead to improved outcomes at a
      lower cost.

PMID- 28755150
TI  - Picosecond excitation energy transfer of allophycocyanin studied in solution and
      in crystals.
AB  - Cyanobacteria perform photosynthesis with the use of large light-harvesting
      antennae called phycobilisomes (PBSs). These hemispherical PBSs contain hundreds
      of open-chain tetrapyrrole chromophores bound to different peptides, providing an
      arrangement in which excitation energy is funnelled towards the PBS core from
      where it can be transferred to photosystem I and/or photosystem II. In the PBS
      core, many allophycocyanin (APC) trimers are present, red-light-absorbing
      phycobiliproteins that covalently bind phycocyanobilin (PCB) chromophores. APC
      trimers were amongst the first light-harvesting complexes to be crystallized. APC
      trimers have two spectrally different PCBs per monomer, a high- and a low-energy
      pigment. The crystal structure of the APC trimer reveals the close distance (~21
      A) between those two chromophores (the distance within one monomer is ~51 A) and
      this explains the ultrafast (~1 ps) excitation energy transfer (EET) between
      them. Both chromophores adopt a somewhat different structure, which is held
      responsible for their spectral difference. Here we used spectrally resolved
      picosecond fluorescence to study EET in these APC trimers both in crystallized
      and in solubilized form. We found that not all closely spaced pigment couples
      consist of a low- and a high-energy pigment. In ~10% of the cases, a couple
      consists of two high-energy pigments. EET to a low-energy pigment, which can
      spectrally be resolved, occurs on a time scale of tens of picoseconds. This
      transfer turns out to be three times faster in the crystal than in the solution.
      The spectral characteristics and the time scale of this transfer component are
      similar to what have been observed in the whole cells of Synechocystis sp. PCC
      6803, for which it was ascribed to EET from C-phycocyanin to APC. The present
      results thus demonstrate that part of this transfer should probably also be
      ascribed to EET within APC trimers.

PMID- 28755151
TI  - IVF oocyte retrieval: prospective evaluation of the type of anesthesia on live
      birth rate, pain, and patient satisfaction.
AB  - PURPOSE: Does the type of anesthesia (paracervical block (PCB) or general
      anesthesia (GA)) impact live birth rate, pain, and patient satisfaction? METHODS:
      A non-randomized prospective cohort study was conducted in women treated for IVF.
      Two groups of patients were prospectively included: the PCB group (n = 234) and
      the GA group (n = 247). The type of anesthesia was determined by the patients.
      The primary endpoint was cumulative live birth rate by OR. Secondary endpoints
      were self-assessment of the patients' peri-operative abdominal and vaginal pain
      vs the doctors' evaluations during PCB, post-operative abdominal and vaginal pain
      level, and patient satisfaction in both groups. Pain levels were assessed with a
      numerical rating scale (NRS). RESULTS: The live birth rate was similar in both
      groups (19.8% in the GA group vs 20.9% in the PCB group, P = 0.764). During
      oocyte retrieval in the PCB group, the physicians significantly under-estimated
      the vaginal pain experienced by the patients (3.04 +/- 0.173 for patients vs 2.59
      +/- 0.113 for surgeons, P = 0.014). Post-operative vaginal and abdominal pain
      were significantly greater in the PCB group compared to the GA group (2.26 +/-
      0.159 vs 1.66 +/- 0.123, respectively, P = 0.005, and 3.80 +/- 0.165 vs 3.00 +/-
      0.148, respectively, P < 0.001). Patients were more significantly satisfied with
      GA than with PBC (P < 0.001). CONCLUSION: Because the LBR was similar in both
      groups and patient satisfaction was high, the choice of anesthesia should be
      decided by the patients.

PMID- 28755152
TI  - Assisted reproduction and risk of preterm birth in singletons by infertility
      diagnoses and treatment modalities: a population-based study.
AB  - PURPOSE: The purpose of this study is to examine the spectrum of infertility
      diagnoses and assisted reproductive technology (ART) treatments in relation to
      risk of preterm birth (PTB) in singletons. METHODS: Population-based assisted
      reproductive technology surveillance data for 2000-2010 were linked with birth
      certificates from three states: Florida, Massachusetts, and Michigan, resulting
      in a sample of 4,370,361 non-ART and 28,430 ART-related singletons. Logistic
      regression models with robust variance estimators were used to compare PTB risk
      among singletons conceived with and without ART, the former grouped by parental
      infertility diagnoses and treatment modalities. Demographic and pregnancy factors
      were included in adjusted analyses. RESULTS: ART was associated with increased
      PTB risk across all infertility diagnosis groups and treatment types: for
      conventional ART, adjusted relative risks ranged from 1.4 (95% CI 1.0, 1.9) for
      male infertility to 2.4 (95% CI 1.8, 3.3) for tubal ligation. Adding intra
      cytoplasmic sperm injection and/or assisted hatching to conventional ART
      treatment did not alter associated PTB risks. Singletons conceived by mothers
      without infertility diagnosis and with donor semen had an increased PTB risk
      relative to non-ART singletons. CONCLUSIONS: PTB risk among ART singletons is
      increased within each treatment type and all underlying infertility diagnosis,
      including male infertility. Preterm birth in ART singletons may be attributed to
      parental infertility, ART treatments, or their combination.

PMID- 28755153
TI  - Selection of mitochondria in female germline cells: is Balbiani body implicated
      in this process?
AB  - Early oocytes of nearly all animal species contain a transient organelle
      assemblage termed the Balbiani body. Structure and composition of this assemblage
      may vary even between closely related species. Despite this variability, the
      Balbiani body always comprises of numerous tightly clustered mitochondria and
      accumulations of nuage material. It has been suggested that the Balbiani body is
      an evolutionarily ancestral structure, which plays a role in various processes
      such as the localization of organelles and macromolecules to the germ plasm,
      lipidogenesis, as well as the selection/elimination of dysfunctional mitochondria
      from female germline cells. We suggest that the selection/elimination of
      mitochondria is a primary and evolutionarily ancestral function of Balbiani body,
      and that the other functions are secondary, evolutionarily derived additions. We
      propose a simple model explaining the role of the Balbiani body in the selection
      of mitochondria, i.e., in the mitochondrial DNA (mtDNA) bottleneck phenomenon.

PMID- 28755154
TI  - Levetiracetam-induced hyponatremia.

PMID- 28755155
TI  - Chemical water quality gradients in the Mongolian sub-catchments of the Selenga
      River basin.
AB  - Even though the Selenga is the main tributary to Lake Baikal in Russia, the
      largest part of the Selenga River basin is located in Mongolia. It covers a
      region that is highly diverse, ranging from almost virgin mountain zones to
      densely urbanized areas and mining zones. These contrasts have a strong impact on
      rivers and their ecosystems. Based on two sampling campaigns (summer 2014, spring
      2015), we investigated the longitudinal water quality pattern along the Selenga
      and its tributaries in Mongolia. While headwater regions typically had a very
      good water quality status, wastewater from urban areas and impacts from mining
      were found to be main pollution sources in the tributaries. The highest nutrient
      concentrations in the catchment were found in Tuul River, and severely elevated
      concentrations of trace elements (As, Cd, Cu, Cr, Fe, Mn, Ni, Pb, Zn), nutrients
      (NH4+, NO2-, NO3-, PO43-), and selected major ions (SO42-) were found in main
      tributaries of Selenga River. Moreover, trace element concentrations during
      spring 2015 (a time when many mines had not yet started operation) were markedly
      lower than in summer 2014, indicating that the additional metal loads measured in
      summer 2014 were related to mining activities. Nevertheless, all taken water
      samples in 2014 and 2015 from the main channel of the Mongolian Selenga River
      complied with the Mongolian standard (MNS 1998) for the investigated parameters.

PMID- 28755156
TI  - Cochrane in CORR (r): Surgical Versus Non-surgical Treatment for Lumbar Spinal
      Stenosis.

PMID- 28755157
TI  - Renal dysfunction after abdominal or thoracic endovascular aortic aneurysm
      repair: incidence and risk factors.
AB  - PURPOSE: To determine the incidence and risk factors of renal dysfunction after
      abdominal endovascular aortic repair (EVAR) and thoracic endovascular aortic
      repair (TEVAR). MATERIALS AND METHODS: The study consisted of 227 patients
      treated with EVAR and 90 with TEVAR for aortic aneurysms. Parameters, including
      patients' background factors, preoperative renal function, contrast dose and
      aortic wall irregularity on CT images were assessed in relation to postoperative
      renal dysfunction. RESULTS: Deterioration of renal function was observed in 33 of
      218 patients (15.1%) after EVAR and in 7 of 79 (8.9%) patients after TEVAR.
      Hemodialysis was required in one patient after EVAR. In EVAR, renal dysfunction
      correlated with age (p = 0.034) and occlusion of accessory renal artery (p =
      0.0001). In TEVAR, renal dysfunction correlated with age (p = 0.021), contrast
      dose (p = 0.042) and irregularity of the descending aortic wall (p = 0.023). In a
      multiple regression analysis, postoperative renal dysfunction was correlated with
      occlusion of accessory renal artery (p = 0.0003) after EVAR, and age (p = 0.02),
      contrast dose (p = 0.026) and irregularity of the descending aortic wall (p =
      0.042) after TEVAR. CONCLUSION: Occlusion of accessory renal artery in EVAR, and
      age, contrast dose and irregularity of the descending aortic wall in TEVAR were
      considered to be predictors of postoperative renal dysfunction.

PMID- 28755159
TI  - Managing Hypertension in the Elderly: What is Different, What is the Same?
AB  - PURPOSE OF REVIEW: The goal is to discuss management of hypertension in the
      elderly. RECENT FINDINGS: At 3.14-year follow-up of 2636 persons >=75 years in
      the Systolic Blood Pressure Intervention Trial (SPRINT), compared with a systolic
      blood pressure (SBP) goal of <140 mmHg, a SBP goal of <120 mmHg reduced the
      primary endpoint of myocardial infarction, other acute coronary syndrome, stroke,
      heart failure, or cardiovascular death by 34% (p = 0.001), all-cause mortality by
      33% (p = 0.009), heart failure by 38% (p = 0.003), and the primary outcome or
      death by 32% (p < 0.001). Absolute cardiovascular event rates were lower for the
      intensive treatment group within each frailty stratum. The incidence of serious
      adverse events was similar in both treatment groups. The SPRINT trial provides
      very important information on the efficacy and safety of lowering the SBP to <120
      mmHg in elderly adults with hypertension.

PMID- 28755158
TI  - Optimizing endothelial cell functionalization for cell therapy of vascular
      proliferative disease using a direct contact co-culture system.
AB  - Increased susceptibility to thrombosis, neoatherosclerosis, and restenosis due to
      incomplete regrowth of the protective endothelial layer remains a critical
      limitation of the interventional strategies currently used clinically to relieve
      atherosclerotic obstruction. Rapid recovery of endothelium holds promise for both
      preventing the thrombotic events and reducing post-angioplasty restenosis,
      providing the rationale for developing cell delivery strategies for accelerating
      arterial reendothelialization. The successful translation of experimental cell
      therapies into clinically viable treatment modalities for restoring vascular
      endothelium critically depends on identifying strategies for enhancing the
      functionality of endothelial cells (EC) derived from high cardiovascular risk
      patients, the target group for the majority of angioplasty procedures. Enhancing
      EC-associated nitric oxide (NO) synthesis by inducing overexpression of NO
      synthase (NOS) has shown promise as a way of increasing paracrine activity and
      restoring function of EC. In the present study, we developed a direct contact co
      culture approach compatible with highly labile effectors, such as NO, and applied
      it for determining the effect of EC functionalization via NOS gene transfer on
      the growth of co-cultured arterial smooth muscle cells (A10 cell line) exhibiting
      the defining characteristics of neointimal cells. Bovine aortic endothelial cells
      magnetically transduced with inducible NOS-encoding adenovirus (Ad) formulated in
      zinc oleate-based magnetic nanoparticles (MNP[iNOSAd]) strongly suppressed growth
      of proliferating A10 and attenuated the stimulatory effect of a potent mitogen,
      platelet-derived growth factor (PDGF-BB), whereas EC functionalization with free
      iNOSAd or MNP formulated with a different isoform of the enzyme, endothelial NOS,
      was associated with lower levels of NO synthesis and less pronounced
      antiproliferative activity toward co-cultured A10 cells. These results show
      feasibility of applying magnetically facilitated gene transfer to potentiate
      therapeutically relevant effects of EC for targeted cell therapy of restenosis.
      The direct contact co-culture methodology provides a sensitive and reliable tool
      with potential utility for a variety of biomedical applications.

PMID- 28755160
TI  - Successful video-assisted thoracoscopic surgery in prone position in patients
      with esophageal cancer and aberrant right subclavian artery: report of three
      cases.
AB  - BACKGROUND: An aberrant right subclavian artery (ARSA) with an associated
      nonrecurrent right inferior laryngeal nerve (NRILN) is a relatively rare anomaly
      that occurs at a frequency of 0.3 to 2.0% of the general population. NRILN has
      been mainly documented in the head and neck region; it has been rarely described
      in patients with esophageal cancer, especially those undergoing thoracoscopic
      surgery. Video-assisted thoracoscopic surgery for esophageal cancer (VATS-E) is
      becoming more widespread as a reliable minimally invasive surgical procedure
      associated with reduced perioperative complications. CASE PRESENTATION: Herein,
      we report three cases of esophageal cancer with ARSA and NRILN which underwent
      successful VATS-E. Case 1, a 53-year-old male who had early stage esophageal
      cancer was performed VATS-E. Upper gastrointestinal (GI) series showed "Bayonet
      sign" (T1aN0M0, pStageIA in UICC). Case 2, a 75-year-old male who had advanced
      esophageal cancer was performed neoadjuvant chemotherapy and following VATS-E.
      This case had right thoracic duct and "Bayonet sign" on upper GI series (T1bN2M0,
      pStage IIIA in UICC). Case3, a 72-year-old male who had advanced esophageal
      cancer was performed neoadjuvant chemotherapy and following VATS-E (T3N2M0,
      pStageIIIB in UICC). All of these three cases were performed VATS-E and
      discharged without any complication. CONCLUSION: VATS-E in the prone position is
      a feasible procedure that can reduce the risk of complications with an enlarged
      and clear view, and knowledge of this type of anomaly is very important for
      surgeons who perform esophagectomy.

PMID- 28755161
TI  - Usefulness of three-dimensional image navigation system for evaluation of hepatic
      artery before living donor liver transplantation: a case report.
AB  - BACKGROUND: The evaluation of the hepatic vascular anatomy in living liver donors
      is increasingly being performed by three-dimensional (3D) computed tomography
      (CT) angiography. However, details of hepatic artery anatomy obtained by 3D CT
      angiography are not always superior to those obtained by angiography. Here, we
      report a case in which the 3D image navigation system helped to detect segment
      II, III, and IV arteries (A2, A3, and A4, respectively) that individually
      originated from the proper hepatic artery (PHA); this could not be detected by 3D
      CT angiography. CASE PRESENTATION: A 46-year-old man with end-stage primary
      biliary cirrhosis was admitted to our hospital for evaluation as a candidate for
      living donor liver transplantation. The patient's younger sister, aged 43 years,
      was the only living donor candidate. The predicted left liver graft volume with
      the middle hepatic vein was found to be 403 mL using the region-growing method
      with 3D CT software. This volume was sufficiently large for the recipient because
      the standard liver volume of the recipient was 1095 mL. 3D CT angiography was
      performed twice but could not reveal the anatomical structure of the left and
      middle hepatic arteries. However, simulation using the region-growing method
      demonstrated individual branching off of A2, A3, and A4 from the PHA;
      conventional angiography demonstrated the same results. Each branch was
      approximately 1 mm in diameter, which was too small for secure anastomosis.
      Therefore, we selected the right liver graft for simplicity. The postoperative
      course of the donor and recipient was uneventful, and they were discharged on
      postoperative days 10 and 46, respectively. CONCLUSIONS: In conclusion,
      reconstruction of the hepatic vasculature using the 3D software by region-growing
      method might be a useful adjunct for surgical planning in the evaluation of the
      hepatic arteries in living liver donors.

PMID- 28755162
TI  - Coexistence of multiple genotypes of porcine epidemic diarrhea virus with novel
      mutant S genes in the Hubei Province of China in 2016.
AB  - The emergence of highly virulent porcine epidemic diarrhea virus (PEDV) variants
      in China caused huge economic losses in 2010. Since then, large-scale sporadic
      outbreaks of PED caused by PEDV variants have occasionally occurred in China.
      However, the molecular diversity and epidemiology of PEDV in different provinces
      has not been completely understood. To determine the molecular diversity of PEDV
      in the Hubei Province of China, we collected 172 PED samples from 34 farms across
      the province in 2016 and performed reverse transcription polymerase chain
      reaction (RT-PCR) by targeting the nucleocapsid (N) gene. Seventy-four samples
      were found to be PEDV-positive. We further characterized the complete spike (S)
      glycoprotein genes from the positive samples and found 21 different S genes with
      amino acid mutations. The PEDV isolates here presented most of the genotypes
      which were found previously in field isolates in East and South-East Asia, North
      America, and Europe. Besides the typical Genotypes I and II, the INDEX groups
      were also found. Importantly, 58 new amino acids mutant sites in the S genes,
      including 44 sites in S1 and 14 sites in S2, were first described. Our results
      revealed that the S genes of PEDV showed variation and that diverse genotypes of
      PEDV coexisted and were responsible for the PED outbreaks in Hubei in 2016. This
      work highlighted the complexity of the epidemiology of PEDV and emphasized the
      need for reassessing the efficacy of classic PEDV vaccines against emerging
      variant strains and developing new vaccines to facilitate the prevention and
      control of PEDV in fields.

PMID- 28755163
TI  - CXCL9-11 polymorphisms are associated with liver fibrosis in patients with
      chronic hepatitis C: a cross-sectional study.
AB  - BACKGROUND AND AIMS: CXCL9-11 polymorphisms are related to various infectious
      diseases, including hepatitis C virus (HCV) infection. In this study, we analyzed
      the association between CXCL9-11 polymorphisms and liver fibrosis in HCV-infected
      patients. METHODS: We performed a cross-sectional study in 389 patients who were
      genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11
      rs4619915) using the Sequenom's MassARRAY platform. The primary outcome variable
      was the liver stiffness measurement (LSM). We established three cut-offs of LSM:
      LSM >= 7.1 kPa (F >= 2-significant fibrosis), LSM >= 9.5 kPa (F >= 3-advanced
      fibrosis), and LSM >= 12.5 kPa (F4-cirrhosis). RESULTS: Recessive, overdominant
      and codominant models of inheritance showed significant values, but the
      overdominant model was the best fitting our data. In this case, CXCL9 rs10336 AG,
      CXCL10 rs3921 CG and CXCL11 rs4619915 AG were mainly associated with lower values
      of LSM [(adjusted GMR (aGMR) = 0.85 (p = 0.005), aGMR = 0.84 (p = 0.003), and
      aGMR = 0.84 (p = 0.003), respectively]. Patients with CXCL9 rs10336 AG genotype
      had lower odds of significant fibrosis (LSM >= 7.1 kPa) [adjusted OR (aOR) = 0.59
      (p = 0.016)], advanced fibrosis (LSM >= 9.5 kPa) [aOR = 0.54 (p = 0.010)], and
      cirrhosis (LSM >= 12.5 kPa) [aOR = 0.56 (p = 0.043)]. Patients with CXCL10 rs3921
      CG or CXCL11 rs4619915 AG genotypes had lower odds of significant fibrosis (LSM
      >= 7.1 kPa) [adjusted OR (aOR) = 0.56 (p = 0.008)], advanced fibrosis (LSM >= 9.5
      kPa) [aOR = 0.55 (p = 0.013)], and cirrhosis (LSM >= 12.5 kPa) [aOR = 0.57 (p =
      0.051)]. Additionally, CXCL9-11 polymorphisms were related to lower liver
      stiffness under a codominant model of inheritance, being the heterozygous
      genotypes also protective against hepatic fibrosis. In the recessive inheritance
      model, the CXCL9 rs10336 AA, CXCL10 rs3921 CC and CXCL11 rs4619915 AA were
      associated with higher LSM values [(adjusted GMR (aGMR) = 1.19 (p = 0.030), aGMR
      = 1.21 (p = 0.023), and aGMR = 1.21 (p = 0.023), respectively]. Moreover,
      patients with CXCL9 rs10336 AA genotype had higher odds of significant fibrosis
      (LSM >= 7.1 kPa) [adjusted OR (aOR) = 1.83 (p = 0.044)] and advanced fibrosis
      (LSM >= 9.5 kPa) [aOR = 1.85 (p = 0.045)]. Furthermore, patients with CXCL10
      rs3921 CC or CXCL11 rs4619915 AA genotypes had higher odds of advanced fibrosis
      (LSM >= 9.5 kPa) [aOR = 1.89 (p = 0.038)]. CONCLUSIONS: CXCL9-11 polymorphisms
      were related to likelihood of having liver fibrosis in HCV-infected patients. Our
      data suggest that CXCL9-11 polymorphisms may play a significant role against the
      progression of CHC and could help prioritize antiviral therapy.

PMID- 28755164
TI  - [Allogeneic transplants for biological reconstruction of bone defects].
AB  - A combination of allogeneic and autologous bone transplants is frequently used
      for the biological reconstruction of bone defects. Autologous bone transplants
      can be used either in the form of structural or cancellous bone transplants. The
      osteogenic potential of autologous cancellous bone is well-known and is still the
      gold standard with respect to osteoinduction and remodelling. Structural
      transplants, such as fibular and tricortical iliac crest grafts can be
      transplanted either free, i.e. non-vascularized or vascularized with anastomosed
      vessels. Allogeneic bone transplants can be used in a spongiose or structural
      form. In revision endoprosthetics the use of allogeneic bone transplants has
      essentially been reduced to impaction grafting, due to the introduction of
      trabecular metal as a permanently stable substitute. Allogeneic transplants have
      been restricted due to 3D-printing and the associated individually adapted
      reconstruction. In individual cases combined reconstruction consisting of
      allograft and endoprosthesis provide the advantage of safe load transmission and
      permanent reconstruction by the endoprosthesis and the possibility of soft tissue
      insertion of the allograft.

PMID- 28755165
TI  - Assessment of intravitreal ocriplasmin treatment for vitreomacular traction in
      clinical practice.
AB  - PURPOSE: To assess treatment effects following intravitreal injection of
      ocriplasmin for vitreomacular traction (VMT), with or without full-thickness
      macular hole (FTMH), in real-life setting. METHODS: This is a monocentric,
      retrospective, consecutive series of 82 eyes from 82 patients who underwent
      ocriplasmin treatment between July 2013 and December 2016. We included 57 eyes
      with pure VMT, 17 eyes with small FTMHs, and eight eyes with medium FTMHs.
      Primary outcome measures were VMT release and MH closure rates. Secondary
      outcomes were visual acuity (VA), morphological changes, and subjective visual
      impairment after 1, 3, and 6 months and at last follow-up. RESULTS: After a
      median follow-up of 10 months, VMT release was achieved by pharmacologic
      vitreolysis in 57% of all eyes, whereas the macular hole closure rate was 32%. In
      those presenting with five or more positive prognostic factors (PPF), eyes with
      pure VMT showed nonsurgical traction release in 88%, and FTMHs were released in
      93%, with a closure rate of 20%. Small FTMHs closed in 41% and medium FTMHs in
      13%. The mean change in VA (LogMAR) was -0.07 +/- 0.24 (median - 0.10) in all
      eyes. Subretinal fluid accumulation and ellipsoid zone changes were seen in 31%
      and 37% of all eyes, respectively. They were more frequent in eyes with traction
      release, but were self-limited. CONCLUSIONS: In a real-life setting, release of
      VMT by ocriplasmin injection can be achieved in the majority of eyes, relying on
      a strict patient selection. Closure of FTMHs rather correlates with hole diameter
      than with presence of PPF, and remains a rare finding in medium FTMHs.

PMID- 28755166
TI  - In regards to the article by Gamba et al.: "Which immobilization is better for
      distal radius fracture? A prospective randomized trial".

PMID- 28755167
TI  - Surgery for greater trochanteric pain syndrome after total hip replacement
      confers a poor outcome.
AB  - PURPOSE: Surgery for greater trochanteric pain syndrome (GTPS) may be indicated
      for cases refractory to conservative measures. We aim to evaluate patient
      reported outcomes and adverse events following surgery. METHODS: Postal
      questionnaires were used to evaluate a consecutive series of 61 bursectomy and
      gluteal fascia transposition (GFT) procedures. Study outcomes were Oxford hip
      score, satisfaction score, visual analogue score, pain lying on the affected
      side, and the duration of pain relief after surgery. RESULTS: We received
      responses regarding 52 procedures at a median of 34 months follow-up; 40% of
      cases of GTPS occurred following THA. We observed a bimodal distribution of
      satisfaction scores. The early post-operative complication rate was 13%; an
      additional seven cases (12%) required further surgery at a later date. Idiopathic
      GTPS had significantly better post-operative satisfaction than GTPS following
      THA, 87.5 vs. 37.5 (p = 0.006); Oxford hip scores, 35 vs. 15 (p = 0.015); and
      visual analogue scores, 20 vs. 73 (p = 0.005). CONCLUSION: We observed overall
      poor outcomes, significant complications and concerning reoperation rates. Cases
      with previous joint replacement were associated with the worst outcomes.

PMID- 28755168
TI  - Comment on the article "Staphylococcus lugdunensis: a neglected pathogen of
      infections involving fracture-fixation devices".

PMID- 28755169
TI  - Characterization of a novel bioemulsifier from Pseudomonas stutzeri.
AB  - This study describes a novel and efficient alasan-like bioemulsifier produced by
      Pseudomonas stutzeri NJtech 11-1, which was isolated from the Shengli Oilfield.
      The strain was found to produce a new and interesting emulsion stabilizer. The
      crude bioemulsifier showed super stability with 50% salinity and broad pH 3-10.
      The emulsion index (EI24) was increased to 100% after heating from 45 to 95 
      degrees C and the emulsion could be stable for at least 30 days. The yield of Ps
      bioemulsifier (pure bioemulsifier) was 0.68 +/- 0.05 mg mL-1. The Ps
      bioemulsifier was composed of carbohydrates (80 +/- 2.6%) and proteins (9.5 +/-
      0.5%). A low concentration (0.2 mg mL-1) of the Ps-bioemulsifier was obtained
      maximum emulsifying activity at pH 7.1 and its emulsifying activity strengthened
      by suitable salinity. Furthermore, Ps-bioemulsifier could also emulsify
      cyclohexane, hexadecane, kerosene, xylene hydrocarbons efficiently. Therefore,
      the Ps-bioemulsifier showed emulsifying characteristics which make it a good
      candidate for potential applications in bioremediation and microbial enhanced oil
      recovery.

PMID- 28755171
TI  - SIRT1 induces resistance to apoptosis in human granulosa cells by activating the
      ERK pathway and inhibiting NF-kappaB signaling with anti-inflammatory functions.
AB  - SIRT1, a member of the sirtuin family, has recently emerged as a vital molecule
      in controlling ovarian function. The aims of the present study were to
      investigate SIRT1 expression and analyze SIRT1-mediated apoptosis in human
      granulosa cells (GCs). Human ovarian tissues were subjected to
      immunohistochemistry for localization of SIRT1 expression. SIRT1 knockdown in a
      human ovarian GC tumor line (COV434) was achieved by small interfering RNA, and
      the relationship between apoptosis and SIRT1 was assessed by quantitative reverse
      transcription polymerase chain reaction and western blotting. We further detected
      SIRT1 expression in human luteinized GCs. Associations among SIRT1 knockdown,
      SIRT1 stimulation (resveratrol) and expression of ERK1/2 and apoptotic regulatory
      proteins were analyzed in cell lines and luteinized GCs. Resveratrol
      downregulated the levels of nuclear factor (NF)-kappaB/p65, but this inhibitory
      effect was attenuated by suppressing SIRT1 activity. The NF-kappaB/p65 inhibitor
      pyrrolidine dithiocarbamate achieved similar anti-apoptosis effects. These
      results suggest that SIRT1 might play an anti-apoptotic role in apoptosis
      processes in GCs, possibly by sensing and regulating the ERK1/2 pathway, which
      has important clinical implications. Thus, our study provides a mechanistic link,
      whereby activation of SIRT1 function might help to sustain human reproduction by
      maintaining GCs as well as oocytes, offering a novel approach for developing a
      new class of therapeutic anti-inflammatory agents.

PMID- 28755170
TI  - Identification and validation of uterine stimulant methylergometrine as a
      potential inhibitor of caspase-1 activation.
AB  - Inflammasomes are intracellular multiprotein complexes of the innate immune
      system. Upon an inflammatory insult, such as infection or intracellular damage, a
      nucleotide-binding oligomerization domain-like receptor (NLR) sensor protein and
      the adaptor protein ASC (apoptosis-associated speck-like protein containing a
      caspase activation and recruitment domain) are assembled to activate protease
      procaspase-1. This protease processes pro-IL-1beta and pro-IL-18 cytokines, which
      are released to induce the inflammatory response. De-regulation of inflammasome
      contributes to the progression of several diseases, such as Alzheimer's disease,
      diabetes, cancer, inflammatory and autoimmune disorders. We herein describe the
      identification of methylergometrine (MEM), a drug currently used as a smooth
      muscle constrictor during postpartum hemorrhage, as an inhibitor of the
      inflammasome complex in ASC-mediated procaspase-1 activation screening. MEM
      inhibits the activation of the nucleotide-binding oligomerization domain-like
      receptor protein 1 (NLRP1) and nucleotide-binding oligomerization domain-like
      receptor protein 3 (NLRP3) inflammasomes in cellular models upon different pro
      inflammatory stimuli. Our results suggest that MEM has the potential to
      reposition in the treatment of inflammatory diseases with the advantages of
      established safety and clinical data.

PMID- 28755172
TI  - Micro lesion effect of the globus pallidus internus with deep brain stimulation
      in Parkinson's disease patients.
AB  - BACKGROUND: The micro-lesion effect (MLE) has been observed in many Parkinson's
      disease (PD) patients after deep brain stimulation (DBS) surgery. For subthalamic
      nucleus (STN) stimulation, the MLE has been reported as a predictor of the long
      term efficacy of DBS. However, the research on the MLE in the globus pallidus
      internus (GPi) is insufficient. In this report, we conducted a study of the
      correlation between the MLE and improvement of GPi DBS. METHODS: From July 2014
      to November 2015, 36 PD patients underwent GPi DBS in our hospital. The patients
      were evaluated before DBS and postoperatively at 24 h, 1 week, 2 weeks, 3 weeks,
      6 months and 1 year. The evaluated items included the following: the UPDRSIII
      score with and without medication, off time per day and severe dyskinesia time
      per day. The dose of L-dopa, magnitude and duration of MLE were also recorded.
      RESULTS: There were 32 patients with a postoperative MLE. In these 32 cases, the
      dose of L-dopa decreased from 960.5 +/- 257.8 mg (range, 550-1550) to 910.4 +/-
      207.5 mg (range, 550-1250). There is a correlation between the magnitude of the
      MLE in UPDRSIII and the improvement degree of DBS at 6 and 12 months compared
      with the preoperative findings when off medication. The duration of the MLE is
      also an indication of the improvement of DBS in the long term when off
      medication. However, there was no correlation with on medication. Compared with
      the preoperative state, the UPDRSIII score, off time and severe dyskinesia time
      had improved postoperatively. CONCLUSIONS: The MLE of GPi is a predictor of PD
      patients who would benefit from DBS in the long term. Medication may have some
      conflicting effects on the MLE. The exact mechanism of the MLE requires further
      exploration.

PMID- 28755173
TI  - Juvenile Myelomonocytic Leukemia: Profile and Outcome.

PMID- 28755174
TI  - Look Up to Diagnose Down!

PMID- 28755175
TI  - Regional variation in hospitalisation and mortality in heart failure: comparison
      of England and Lombardy using multistate modelling.
AB  - Heart failure (HF) is a common, serious chronic condition with high morbidity,
      hospitalisation and mortality. The healthcare systems of England and the northern
      Italian region of Lombardy share important similarities and have comprehensive
      hospital administrative databases linked to the death register. We used them to
      compare admission for HF and mortality for patients between 2006 and 2012 (n =
      37,185 for Lombardy, 234,719 for England) with multistate models. Despite close
      similarities in age, sex and common comorbidities of the two sets of patients, in
      Lombardy, HF admissions were longer and more frequent per patient than in
      England, but short- and medium-term mortality was much lower. English patients
      had more very short stays, but their very elderly also had longer stays than
      their Lombardy counterparts. Using a three-state model, the predicted total time
      spent in hospital showed large differences between the countries: women in
      England spent an average of 24 days if aged 65 at first admission and 19 days if
      aged 85; in Lombardy these figures were 68 and 27 days respectively. Eight-state
      models suggested disease progression that appeared similar in each country.
      Differences by region within England were modest, with London patients spending
      more time in hospital and having lower mortality than the rest of England. Whilst
      clinical practice differences plausibly explain these patterns, we cannot
      confidently disentangle the impact of alternatives such as coding, casemix, and
      the availability and use of non-hospital settings. We need to better understand
      the links between rehospitalisation frequency and mortality.

PMID- 28755176
TI  - Overflow models for the admission of intensive care patients.
AB  - An earlier article, inspired by overflow models in telecommunication systems with
      multiple streams of telephone calls, proposed a new analytical model for a
      network of intensive care units (ICUs), and a new patient referral policy for
      such networks to reduce the blocking probability of external emergency patients
      without degrading the quality of service (QoS) of canceled elective operations,
      due to the more efficient use of ICU capacity overall. In this work, we use
      additional concepts and insights from traditional teletraffic theory, including
      resource sharing, trunk reservation, and mutual overflow, to design a new patient
      referral policy to further improve ICU network efficiency. Numerical results
      based on the analytical model demonstrate that our proposed policy can achieve a
      higher acceptance level than the original policy with a smaller number of beds,
      resulting in improved service for all patients. In particular, our proposed
      policy can always achieve much lower blocking probabilities for external
      emergency patients while still providing sufficient service for internal
      emergency and elective patients. In addition, we provide new accurate and
      computationally efficient analytical approximations for QoS evaluation of ICU
      networks using our proposed policy. We demonstrate numerically that our new
      approximation method yields more accurate, robust and conservative results
      overall than the traditional approximation. Finally, we demonstrate how our
      proposed approximation method can be applied to solve resource planning and
      optimization problems for ICU networks in a scalable and computationally
      efficient manner.

PMID- 28755177
TI  - Evidence Base for Multidisciplinary Care of Pediatric/Adolescent Bariatric
      Surgery Patients.
AB  - PURPOSE OF REVIEW: Severe childhood obesity, defined as having a body mass index
      (BMI) greater than the 99th percentile for age and gender, is rising in most
      countries and is associated with early morbidity and mortality. Optimal
      management of the health of the child with obesity requires a multidisciplinary
      approach that identifies and treats associated derangements. RECENT FINDINGS:
      Lifestyle interventions such as diet, exercise, and behavioral therapy for the
      severely obese pediatric patient are generally not effective. Few centers
      worldwide offer bariatric surgery for adolescents in a multidisciplinary setting,
      and we are the only center that offers a multidisciplinary approach that
      incorporates bariatric surgery for severely obese children and adolescents across
      all age groups. In this paper, we review up-to-date evidence in this subject
      including ours, and provide details on the multidisciplinary approach to
      pediatric obesity that accommodates bariatric surgery for children across all age
      groups.

PMID- 28755178
TI  - Obesity in International Migrant Populations.
AB  - PURPOSE OF REVIEW: This review examines the risk of obesity in migrant groups
      specifically migrants from countries with lower prevalence of obesity to
      countries with higher prevalence of obesity. We examine obesity prevalence within
      migrant groups compared with native populations and the evidence on factors that
      might shape obesity risk in these migrant groups. RECENT FINDINGS: Migrants may
      arrive in new countries with a health advantage including generally a healthier
      body weight. Genetic and epi-genetic factors, as well as body size preference,
      socio-economic factors, and stress exposure, may play a role in increasing
      unhealthy weight gain in migrant populations. This unhealthy weight gain leads to
      similar or greater obesity risk in migrant populations compared with native
      populations 10-15 years after migration. Meeting the challenge of prevention and
      treatment of obesity in diverse populations will require greater attention to
      minority groups in research in the future.

PMID- 28755179
TI  - Evidence Base for Optimal Preoperative Preparation for Bariatric Surgery: Does
      Mandatory Weight Loss Make a Difference?
AB  - PURPOSE OF REVIEW: Preoperative weight loss regimens prior to bariatric surgery
      have been a routine and common practice for many centers, in the US and around
      the world. The mandated participation in such programs has largely been
      influenced by loco-regional payer requirements. The relationship between
      adherence to a mandatory weight loss regimen and achieved preoperative weight
      loss as well as the clinical impact of preoperative weight loss on bariatric
      outcomes remains uncertain. RECENT FINDINGS: This review examines the available
      current literature, in the context of previous findings, regarding the impact of
      mandated preoperative weight loss regimens and mandatory weight loss on bariatric
      outcomes. The reviewed studies do not provide sufficient evidence that mandatory
      participation in a preoperative weight loss regimen prior to bariatric surgery is
      associated with achieved weight loss or durable bariatric outcome benefit.
      Preoperative weight loss, when achieved, may confer a positive benefit on
      postoperative complications; however, this is not a consistent finding in the
      literature and requires further validation. The practice of mandating
      participation in a preoperative weight loss regimen or requiring mandatory weight
      loss prior to bariatric surgery is not supported by current literature and may
      serve as an obstacle to medically necessary and potentially life-saving
      treatment.

PMID- 28755180
TI  - Discovery of Hereditary Tyrosinemia in Saguenay- Lac St-Jean.
AB  - Given the interest of many people and families directly or indirectly affected by
      hereditary tyrosinemia (HT1), I have tried to give my view on the history of the
      disease from 1965 to 2015 (Fig. 1.1).

PMID- 28755181
TI  - Biochemical and Clinical Aspects of Hereditary Tyrosinemia Type 1.
AB  - Inborn errors of metabolism (IEMs) are a group of diseases involving a genetic
      defect that alters a metabolic pathway and that presents usually during infancy.
      The tyrosine degradation pathway contains five enzymes, four of which being
      associated with IEMs. The most severe metabolic disorder associated with this
      catabolic pathway is hereditary tyrosinemia type 1 (HT1; OMIM 276700). HT1 is an
      autosomal recessive disease caused by a deficiency of fumarylacetoacetate
      hydrolase (FAH), the last enzyme of the tyrosine catabolic pathway. Although a
      rare disease worldwide, HT1 shows higher incidence in certain populations due to
      founder effects. The acute form of the disease is characterized by an early onset
      and severe liver failure while the chronic form appears later and also involves
      renal dysfunctions. Until 1992 the only treatment for this disease was liver
      transplantation. Since then, NTBC/Nitisone (a drug blocking the pathway upstream
      of FAH) is successfully used in combination with a diet low in tyrosine and
      phenylalanine, but patients are still at risk of developing hepatocellular
      carcinoma. This chapter summarizes the biochemical and clinical features of HT1.

PMID- 28755182
TI  - Molecular Aspects of the FAH Mutations Involved in HT1 Disease.
AB  - Hereditary tyrosinemia type 1 (HT1) is caused by the lack of fumarylacetoacetate
      hydrolase (FAH), the last enzyme of the tyrosine catabolic pathway. Up to now,
      around 100 mutations in the FAH gene have been associated with HT1, and despite
      many efforts, no clear correlation between genotype and clinical phenotype has
      been reported. At first, it seems that any mutation in the gene results in HT1.
      However, placing these mutations in their molecular context allows a better
      understanding of their possible effects. This chapter presents a closer look at
      the FAH gene and its corresponding protein in addition to provide a complete
      record of all the reported mutations causing HT1.

PMID- 28755183
TI  - Molecular Pathogenesis of Liver Injury in Hereditary Tyrosinemia 1.
AB  - Untreated HT1 rapidly degenerates into very severe liver complications often
      resulting in liver cancer. The molecular basis of the pathogenic process in HT1
      is still unclear. The murine model of FAH-deficiency is a suitable animal model,
      which represents all phenotypic and biochemical manifestations of the human
      disease on an accelerated time scale. After removal of the drug 2-(2-N-4
      trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), numerous signaling pathways
      involved in cell proliferation, differentiation and cancer are rapidly
      deregulated in FAH deficient mice. Among these, the Endoplasmic reticulum (ER)
      pathway, the heat stress response (HSR), the Nrf2, MEK and ERK pathways, are
      highly represented. The p21 and mTOR pathways critical regulators of
      proliferation and tumorigenesis have also been found to be dysregulated. The
      changes in these pathways are described and related to the development of liver
      cancer.

PMID- 28755184
TI  - Tyrosinemia and Liver Transplantation: Experience at CHU Sainte-Justine.
AB  - Tyrosinemia is a disease of the tyrosine metabolism, affecting mainly liver,
      kidney and peripheral nerves. Two forms of liver disease caused by a deficiency
      of FAH are recognised: (1) acute liver failure; (2) chronic liver disease. Since
      the introduction of NTBC [2-(2-nitro-4-trifluoromethyl benzoyl)-1-3
      cyclohexanedione] (nitisinoneR) in the treatment of tyrosinemia, no liver disease
      has been observed when started in the first weeks of life. Liver transplantation
      is a good option for the treatment of tyrosinemic patients developing liver
      nodules, with high suspicion of hepatocarcinoma. In the long-term outcome of the
      liver transplant, survival was of 90% in tyrosinemic patients.

PMID- 28755185
TI  - The Liver in Tyrosinemia Type I: Clinical Management and Course in Quebec.
AB  - HT1 is a severe autosomal recessive disorder due to the deficiency of
      fumarylacetoacetate hydrolase (FAH), the final enzyme in the degradation of
      tyrosine. Before the era of treatment with 2-(2-N-4-trifluoromethylbenzoyl)-1,3
      cyclohexanedione (NTBC), even with newborn screening and optimal diet therapy,
      HT1 patients often developed liver failure. Death was common in patients who did
      not undergo liver transplantation. For the last two decades, NTBC has
      revolutionized the management of HT1 patients. In screened newborns treated
      within the first month of life, we have not observed hepatocarcinoma. If patients
      are not detected at birth by neonatal screening, the diagnosis and treatment must
      be performed on an emergency basis, and patients are at risk for complications.
      Long term adhesion to treatment and reliable early detection of hepatocellular
      carcinoma (HCC) are two important challenges. In this chapter, we describe the
      clinical, biological, histo-pathological and imaging findings of HT1 in Quebec
      before the era of NTBC. We also describe the hepatic status of nontransplanted
      tyrosinemic patients in Quebec and current management practices in the Quebec
      NTBC Study.

PMID- 28755186
TI  - Liver Transplantation for Hereditary Tyrosinaemia Type 1 in the United Kingdom.
AB  - Fourteen children have undergone liver transplantation for hereditary
      tyrosinaemia type 1 (HT1) at Birmingham Children's hospital (BCH) since 1989; six
      were treated prior to the availability of Nitisinone in 1993 and eight in the
      post Nitisinone era. Prior to 1993 essentially all children with HT1 were
      referred for transplantation. In the Nitisinone era only those with unresponsive
      liver failure or suspected malignancy were considered for transplantation. Those
      who were treated pre-emptively following newborn screening have no evidence of
      liver disease and none have required transplantation.Absolute patient survival is
      86% for the whole group and 100% in the Nitisinone era. There has been a
      functional correction of the metabolic defect in all cases allowing a normal
      diet. Persistent renal succinylacetone production was universal but did not
      appear to have any clinical consequence. Renal function appeared better, and
      hypertension less common in those treated in the Nitisinone era.Outcome was
      poorer for those four children with established malignancy; one was unfit for
      transplantation and another developed a pulmonary metastasis, which was
      successfully resected.

PMID- 28755187
TI  - NTBC and Correction of Renal Dysfunction.
AB  - Hereditary tyrosinemia type 1 (HT1) is characterized by severe progressive liver
      disease and renal tubular dysfunction. Kidney involvement is characterized by
      hypophosphatemic rickets and Fanconi syndrome. Different animal models were
      useful to investigate the pathophysiology of the disease and the effects of NTBC
      therapy on liver and kidney function. NTBC has revolutionized the prognosis of
      HT1 and its acute and chronic effects on renal tubular function have been proved,
      with normalization of tubular function within a few weeks, particularly
      hypophosphatemia and proteinuria. NTBC therapy is highly effective in improving
      renal function both at short and long-term. However, its efficacy critically
      depends on the age at start of treatment with normal outcome in patients
      diagnosed at birth by newborn screening.

PMID- 28755188
TI  - Liver Cancer in Tyrosinemia Type 1.
AB  - Hereditary Tyrosinemia type I (HT1) is clinically mainly characterised by severe
      liver disease. Most patients present in their first months of life with liver
      failure, but others can present later with issues of compensated cirrhosis, renal
      tubulopathy or acute intermittent porphyria. If patients survive the acute phase
      with liver failure or if they present later with compensated cirrhosis, they
      often develop hepatocellular carcinoma early but also later in life. The course
      of the disease changed after the introduction of 2-(2 nitro-4-3 trifluoro
      methylbenzoyl)-1, 3-cyclohexanedione (NTBC), which blocks the tyrosine
      degradation pathway at an earlier step. Therefore, the toxic products did not
      accumulate anymore and all clinical problems resolved. However, the risk
      (although clearly decreased) for developing liver cancer remained, especially if
      NTBC treatment is initiated late, a slow decrease of the tumor marker alpha
      fetoprotein is seen or if the alpha-fetoprotein concentrations remain just above
      the normal range. A rise of alpha-fetoprotein in these HT1 patients is more or
      less pathognomonic for liver cancer. Although hepatoblastoma development occurs
      in HT1 patients, most HT1 patients develop hepatocellular carcinoma (HCC) or a
      mixed type of carcinoma consisting of HCC and hepatoblastoma. Due to the small
      risk of liver cancer development, screening for liver cancer (especially HCC) is
      still recommended in HT1 patients using regular measures of alpha-fetoprotein and
      imaging. Ultrasound is mostly the modality of choice for surveillance, because it
      is widely available, it does not use radiation and is noninvasive. When a
      suspicious lesion is present, the higher sensitivity of MRI could be used for
      characterization and staging of lesions. At this moment, no HCC development in
      pre-symptomatically treated patients is reported. These different situations
      could possibly indicate that NTBC can prevent the start of the development of HCC
      when initiated early, but can't stop the development of HCC if it is prescribed
      at a later stage, stressing the importance of early diagnosis.

PMID- 28755189
TI  - Neurological and Neuropsychological Problems in Tyrosinemia Type I Patients.
AB  - Clinically, Hereditary Tyrosinemia type I (HTI) is especially characterized by
      severe liver dysfunction in early life. However, recurrent neurological crises
      are another main finding in these patients when they are treated with a tyrosine
      and phenylalanine restricted diet only. This is caused by the accumulation of
      delta-aminolevulinic acid due to the inhibitory effect of succinylacetone on the
      enzyme that metabolizes delta-aminolevulinic acid. Due to the biochemical and
      clinical resemblance of these neurological crises and acute intermittent
      porphyria, this group of symptoms in HTI patients is mostly called porphyria-like
      syndrome. The neurological crises in HTI patients disappeared after the
      introduction of treatment with 2-(2 nitro-4-3 trifluoro-methylbenzoyl)-1, 3
      cyclohexanedione (NTBC). However, if NTBC treatment is stopped for a while,
      severe neurological dysfunction will reappear.If NTBC treatment is started early
      and given continuously, all clinical problems seem to be solved. However, recent
      research findings indicate that HTI patients have a non-optimal neurocognitive
      outcome, showing (among others) a lower IQ and impaired executive functioning and
      social cognition. Unfortunately the exact neuropsychological profile of these HTI
      patients is not known yet, neither are the exact pathophysiological mechanisms
      underlying these impairments. It may be hypothesized that the biochemical changes
      such as high blood tyrosine or low blood phenylalanine concentrations are
      important in this respect, but an direct toxic effect of NTBC or production of
      toxic metabolites (that previously characterized the disease before introduction
      of NTBC) cannot be excluded either. This chapter discusses the neurological and
      neuropsychological symptoms associated with HTI in detail. An extended section on
      possible underlying pathophysiological mechanisms of such symptoms is also
      included.

PMID- 28755190
TI  - Diagnosing Hepatorenal Tyrosinaemia in Europe: Newborn Mass Screening Versus
      Selective Screening.
AB  - Hepatorenal tyrosinaemia (HT1) is a serious condition that used to be fatal
      before the advent of nitisinone (NTBC, Orfadine(r)) as a therapeutic option. We
      have recently shown that selective screening is inadequate as initial symptoms
      are often uncharacteristic which leads to a considerable delay in diagnosis and
      treatment. This has a negative impact on morbidity and mortality as well as long
      term outcome. For example, the odds ratio to develop hepatocellular carcinoma is
      12.7 when treatment is initiated after the first birthday compared to start of
      treatment in the neonatal period. Timely diagnosis is only possible when neonatal
      mass screening is operational. HT1 meets all the criteria for neonatal mass
      screening at a clinical and analytical level. The natural course of the disease
      is well known, clinically there is a latent phase in most patients when
      presymptomatic treatment can be initiated. There are no mild phenotypes which do
      not require treatment. Using succinylacetone as the screening parameter a highly
      specific and sensitive test is available with acceptable financial burden.
      Neonatal mass screening for HT1 is acceptable to the target population as it can
      be performed simultaneously with the already existing screening tests in dried
      blood, there are no false negative and false positive cases and the financial
      burden to the health system is moderate. An efficient treatment is available with
      nitisinone and protein-reduced diet supplemented with special amino acid
      mixtures. Despite compelling evidence in favour of a neonatal mass screening for
      HT1 only 57% of European centres taking part in our recent cross-sectional study
      have included HT1 in their newborn screening programme.

PMID- 28755191
TI  - Tyrosinemia Type I in Japan: A Report of Five Cases.
AB  - Tyrosinemia type I in Japan was reported for the first time in 1957 by Sakai et
      al. (Jikei Med J 2:1-10, 1957) and Kitagawa et al. (Proc Jpn Acad Ser B 88:192
      200, 1957). Five cases of patients with tyrosinemia type I were reported to be
      definitively diagnosed in Japan. The first case was reported by Sakai et al. and
      Kitagawa et al. To the best of our knowledge, this was the first definite report
      in the world. The second and third cases were those of a brother and a sister who
      underwent liver transplantation and who were the children of a Japanese-descent
      migrant worker; the fourth case was that of a girl who underwent liver
      transplantation after 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione
      (NTBC) treatment, which was reported by Hata et al.; and the fifth case was that
      of a patient who was administered NTBC, which was reported by Ito et al. These
      were of the subacute type, wherein residual activity was considerably present.
      When combined therapy with a low phenylalanine and tyrosine diet and NTBC
      administration is started after early diagnosis, patients can survive without
      liver transplantation. Development of liver cancer is not found in the cases in
      Japan, but performing liver transplantation without delay is necessary when liver
      cancer is found.

PMID- 28755192
TI  - Newborn Screening for Hereditary Tyrosinemia Type I in Quebec: Update.
AB  - Hereditary tyrosinemia type I (HTI) is a rare autosomal recessive disorder caused
      by a fumarylacetoacetate hydrolase (FAH) deficiency. If untreated, its acute form
      is characterized by hepatic failure, renal dysfunction and neurological crisis,
      and may lead to death. Due to a genetic founder effect in the French-Canadian
      population, the prevalence of HTI is increased in the province of Quebec (1/19
      819), with the IVS12 + 5G>A (1062 + 5G>A) splice site mutation responsible for
      more than 90% of mutated alleles. Universal newborn screening for (HT1) was thus
      established in 1970, and close to four million infants have been tested so far,
      allowing to identify 185 of the 190 affected newborns. During the 1970-1997
      period, 2,249,000 newborns were screened at 3-7 days of life on dried filter
      paper blood spots by tyrosine (Tyr) concentration followed by indirect
      colorimetric semi-quantitative and quantitative (Q) succinylacetone (SA) testing
      (red blood cells delta-aminolevulinate dehydratase inhibition), with
      immunoreactive FAH as the confirmatory test. This approach allowed to identify
      118 of 123 affected newborns. In 1998, owing to earlier hospital discharge and
      increased rate of breastfeeding, four cases were missed within the same year as
      the discriminating power of blood Tyr became inadequate. Thus, the screening
      algorithm was modified: indirect semi-quantitative SA measurement became the
      first-tier test between 1998 and 2014, and direct SA measurement by tandem mass
      spectrometry (MS/MS) was implemented in 2014, followed by indirect quantitative
      SA measurement as second tier test. Confirmation is performed by plasmatic amino
      acid profile and molecular testing. During the 1998-2016 period, more than 1,5
      million neonates have been tested (90% sampled between 24 and 48 h of life): 67
      of the 67 HTI cases were identified. Both indirect and direct SA measurement as
      the initial HTI screening test proved to be highly sensitive and specific, with
      positive and negative predicting value of 79% and 100% respectively.

PMID- 28755193
TI  - Hepatorenal Tyrosinemia in Mexico: A Call to Action.
AB  - Hepatorenal tyrosinemia is a treatable metabolic disease characterized by
      progressive liver failure, renal damage and pronounced coagulopathy. Its clinical
      diagnosis is difficult because of its low prevalence and heterogeneous symptoms.
      In developed countries, expanded newborn screening, based on succinylacetone
      quantification by tandem mass spectrometry, has been very valuable in the early
      detection of hepatorenal tyrosinemia, providing the opportunity for rapid
      treatment of affected patients. In developing countries without systematic
      expanded newborn screening, however, diagnosis and treatment of this disease
      remain major challenges, as genetic diseases in these countries are not a health
      priority and there are few referral centers for infants with inherited errors of
      metabolism. This chapter describes the diagnosis, follow-up and outcome of 20
      Mexican patients with hepatorenal tyrosinemia. This chapter also constitutes a
      call to action to pediatricians, gastroenterologists, geneticists and other
      health professionals, and to academic organizations, health authorities and
      patient advocacy groups, to promote early patient detection and treatment,
      reducing the unacceptably high mortality rate (75%) in Mexican infants with this
      potentially deadly but eminently treatable condition.

PMID- 28755194
TI  - Hereditary Tyrosinemia Type 1 in Turkey.
AB  - Hereditary tyrosinemia type 1 (HT1, OMIM 276700) is a rare autosomal recessively
      inherited inborn error of metabolism in the tyrosine catabolic pathway due to
      deficiency of the enzyme fumarylacetoacetate hydrolase. The clinical features of
      HT1 are widely heterogenous even within the same family members. Clinical
      features includes acute or chronic liver disease with increased risk of
      hepatocellular carcinoma, hypophosphatemic rickets due to renal tubular
      dysfunction, glomerulosclerosis, failure to thrive, neurological porphyria-like
      crisis, hypertrophic cardiomyopathy and hypoglycemia due to hyperinsulinism.
      Currently, the treatment in HT1 consists of two principles: inhibition of the
      formation of toxic metabolites by nitisinone [2-(2-nitro-4
      trifluoromethylbenzoyl)-1,3-cyclohexanedione; NTBC] and reduction of tyrosine
      levels by dietary treatment. In this chapter besides presenting the data for 42
      patients that had been followed up by Pediatric Metabolic Diseases and Nutrition
      Unit, Cerrahpasa Medical Faculty, Istanbul University, we also evaluated the data
      abstracted from the previously published case studies in order to better
      understand the disease course and gain further insight in the current diagnosis
      and treatment for HT1 in Turkey.

PMID- 28755195
TI  - From Weed Killer to Wonder Drug.
AB  - The discovery that a natural product leptospermone had herbicidal activity formed
      the starting point for chemical synthesis to find more activity and selectivity.
      A series of molecules called triketones were found to possess good activity and 2
      (2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) was selected for
      toxicology testing. NTBC fed at low doses to rats and dogs caused keratopathy,
      which on cessation of the diet recovered. Mice, rabbits and monkeys fed NTBC did
      not show this response. Research discovered that NTBC caused tyrosinaemia which
      was due to inhibition of the enzyme 4-hydroxyphenylpyruvate dioxygenase in both
      mammals and plants thereby finding a novel target for killing plants. NTBC was
      also used sucessfully as a drug to treat a rare inborn error of metabolism,
      tyrosinaemia type I, in collaboration with Professor's Sven Lindstedt and
      Elisabeth Holme. Understanding the mechanism of toxicity of NTBC led to novel
      herbicide discovery and saved the lives of children with acute tyrosinaemia type
      I.

PMID- 28755196
TI  - The Quebec NTBC Study.
AB  - In this chapter we describe the current Quebec NTBC Study protocol. Quebec's
      unique characteristics have influenced the development of the protocol, including
      a high prevalence of hepatorenal tyrosinemia (HT1), universal newborn screening
      for HT1, availability of treatment with nitisinone (NTBC) and special diet, a
      large territory, where HT1 treatment is coordinated by a small number of centers.
      Screened newborns are seen within 3 weeks of birth. Patients with liver
      dysfunction (prolonged prothrombin time and/or international normalized ratio
      (INR) provide sensitive, rapidly available indicators) are treated by NTBC and
      special diet. The specific diagnosis is confirmed by diagnostic testing for
      succinylacetone (SA) in plasma and urine samples obtained before treatment. After
      an initial period of frequent surveillance, stable patients are followed every 3
      months by assay of plasma amino acids and NTBC and plasma and urine SA. Abdominal
      ultrasound is done every 6 months. Patients have an annual visit to the
      coordinating center that includes multidisciplinary evaluations in metabolic
      genetics, hepatology, imaging (for abdominal ultrasound and magnetic resonance
      imaging) and other specialties as necessary. If hepatocellular carcinoma is
      suspected by imaging and/or because of progressive elevation of alphafetoprotein,
      liver transplantation is discussed. To date, no patient in whom treatment was
      started before 1 month of age has developed hepatocellular carcinoma, after
      surveillance for up to 20 years in some. This patient group is the largest in the
      world that has been treated rapidly following newborn screening. The protocol
      continues to evolve to adapt to the challenges of long term surveillance.

PMID- 28755197
TI  - Dietary Considerations in Tyrosinemia Type I.
AB  - Since the introduction of 2-(2 nitro-4-3 trifluoro-methylbenzoyl)-1, 3
      cyclohexanedione (NTBC), life expectancy of HT1 patients greatly improved.
      However, due to treatment with NTBC, tyrosine concentrations greatly increase. As
      a consequence to possible neurocognitive problems, the main objective of dietary
      therapy in HT1 is to provide adequate nutrition allowing normal growth and
      development while strictly controlling tyrosine levels in blood (and tissues).
      Although no well-defined target levels exist, tyrosine concentrations below 400
      MUmol/L are considered to be safe. To achieve this aim a diet restricted in
      natural protein and supplemented with a special tyrosine and phenylalanine-free
      amino acid mixture is necessary.Dietary management could be strenuous at
      diagnosis due to several different problems. If vomiting and diarrhea are a major
      issue at diagnosis, frequent feeding with additional energy from low protein food
      is needed for catch-up growth. Initiation of dietary treatment is usually easier
      if diagnosis is directly after birth. Based on newborn screening when infants are
      still reasonable healthy. If presenting clinically infants may experience serious
      difficulties in taking the amino acid mixtures probably due to feeding problems
      while when presenting after some 2-3 months taste development and the difference
      in the taste of amino acid mixtures compared to regular formula and breast milk
      increase difficulties with the treatment.Following a dietary treatment is even
      harder than taking some medicine. Older children and adolescents often relax the
      diet and at some age become reluctant to stick to a strict regimen. Therefore,
      adequate training and information should be given to the patients and the family
      at regular intervals. To achieve this, a multidisciplinary approach involving
      pediatricians/physicians, dieticians, psychologists and social workers is an
      asset for the care of patients with HT1.

PMID- 28755198
TI  - Remaining Challenges in the Treatment of Tyrosinemia from the Clinician's
      Viewpoint.
AB  - This chapter provides a clinical perspective on the challenges that stand between
      current clinical practice and a cure for hepatorenal tyrosinemia (HT1). HT1 has
      been transformed in the last 50 years from an aggressive often undiagnosed
      childhood disease causing liver failure or liver cancer, with infant death in
      most patients, to a condition that is detectable at birth, and for which
      treatment with nitisinone (NTBC) and diet can prevent detectable liver or kidney
      abnormalities. What challenges remain? The properties of the affected metabolic
      pathway and the broad spectrum of severity seen in untreated patients are
      incompletely understood but potentially important for patients. Available
      treatments have potential complications, including liver transplantation (risks
      of surgery and of immunosuppression to prevent rejection), nitisinone and diet
      therapy (hypertyrosinemia, corneal opacities, nutritional imbalances and possibly
      developmental delay). The detection of liver cancer is imperfect and laborious.
      The effects of tyrosinemia during pregnancy are little-known. Although animal
      models of HT1 are becoming standard research tools in cell replacement and gene
      modification therapy, these techniques are not currently applicable to HT1
      itself. Treatment adherence is variable, causing concern about long term outcome
      for some patients. Around the world, there are great disparities in the diagnosis
      and treatment of HT1. Most affected individuals are born in places where newborn
      screening for HT1 is not performed and where appropriate treatment is not
      available. We hope that this list will help to focus on some of these remaining
      obstacles to a cure for HT1.

PMID- 28755199
TI  - Fah Knockout Animals as Models for Therapeutic Liver Repopulation.
AB  - Several animal models of Fah deficiency have been developed, including mice, pigs
      and most recently rats. Initially, the murine models were developed with the
      intent to mirror the human disease for pathophysiologic and therapeutic studies.
      However, it soon became apparent that Fah-positive hepatocytes have a potent
      selective growth advantage in mutant liver and can extensively repopulate the
      diseased organ. For this reason, Fah mutant mice have become a workhorse for
      liver biology and are widely used in liver stem cell and hepatic gene therapy
      research. Immune deficient Fah-knockout mice can be repopulated with human
      hepatocytes, creating "mice with human livers". These chimeric animals have
      become an important preclinical model for infectious diseases, metabolism and
      gene therapy. The potent expansion of human hepatocytes in Fah knockout mice has
      given rise to the concept of using Fah mutants as living bioreactors to produce
      large quantities of fully mature hepatocytes. As a consequence, larger animal
      models of Fah deficiency have recently been developed.

PMID- 28755200
TI  - Gene Therapy in Tyrosinemia: Potential and Pitfalls.
AB  - In this chapter, we intend to review gene therapy concepts applied to the
      potential treatment of tyrosinemia for parents and pediatricians. Therefore, our
      main objective is to give general informations in a comprehensible manner.
      Considering the nature of tyrosinemia and the current state of technology, a
      particular focus will be put on strategies using viral delivery of DNA to the
      liver. In light of the recent development of the CRISPR technology and the
      revival of promises for previously unavailable therapeutical tools, the present
      chapter aims at presenting up to date facts and potential pitfalls towards an
      application for metabolic diseases, in particular tyrosinemia.

PMID- 28755201
TI  - Update on the Diagnosis and Treatment of Spontaneous Intracranial Hypotension.
AB  - PURPOSE OF REVIEW: The purpose of this study is to provide an update on recent
      developments in the understanding, diagnosis, and treatment of spontaneous
      intracranial hypotension (SIH). RECENT FINDINGS: SIH is an important cause of
      headaches caused by spinal cerebrospinal fluid (CSF) leaks, with an increasingly
      broad spectrum of clinical presentations and diagnostic findings. A simple
      conception of the condition as being defined by the presence of low CSF pressure
      is no longer sufficient or accurate. A number of etiologies for spinal CSF leaks
      have been identified, including the recent discovery of CSF-venous fistulas, and
      these various etiologies may require different diagnostic and therapeutic
      pathways in order to affect a cure. Familiarity with the spectrum of
      presentations and causes of SIH is critical to accurate and timely diagnosis and
      management. Challenges exist in both diagnosis and treatment, and require
      understanding of the underlying pathogenesis of the condition in order to
      appropriately select testing and treatment. Prospective studies are needed going
      forward in order to inform workup and guide treatment decisions.

PMID- 28755202
TI  - The symbol of spread of modern Western botany into China: Chih-wu hsueh, an
      unconventional translation in the late Qing dynasty.

PMID- 28755204
TI  - Dr. Chi-Ming Chu: Respected founder of molecular virology and pioneer of
      biologicals in China.

PMID- 28755203
TI  - MicroRNAs recruit eIF4E2 to repress translation of target mRNAs.
AB  - MicroRNAs (miRNAs) recruit the RNA-induced silencing complex (RISC) to repress
      the translation of target mRNAs. While the 5' 7-methylguanosine cap of target
      mRNAs has been well known to be important for miRNA repression, the underlying
      mechanism is not clear. Here we show that TNRC6A interacts with eIF4E2, a
      homologue of eIF4E that can bind to the cap but cannot interact with eIF4G to
      initiate translation, to inhibit the translation of target mRNAs. Downregulation
      of eIF4E2 relieved miRNA repression of reporter expression. Moreover, eIF4E2
      downregulation increased the protein levels of endogenous IMP1, PTEN and PDCD4,
      whose expression are repressed by endogenous miRNAs. We further provide evidence
      showing that miRNA enhances eIF4E2 association with the target mRNA. We propose
      that miRNAs recruit eIF4E2 to compete with eIF4E to repress mRNA translation.

PMID- 28755205
TI  - Tubulointerstitial capillaries limited intravascular lymphoma of the kidney.

PMID- 28755206
TI  - Myelomonocytic leukemia with intracytoplasmic crystalline inclusions, double
      minute chromosomes and MYC amplification.

PMID- 28755207
TI  - Use of Prazosin for Pediatric PTSD-Associated Nightmares and Sleep Disturbances:
      A Retrospective Chart Review.
AB  - INTRODUCTION: Youth exposed to trauma have an increased risk for developing
      posttraumatic stress disorder (PTSD) and associated sleep disturbances and
      nightmares. The alpha-1 antagonist prazosin reduces sleep disturbances and
      nightmares in adults with PTSD; however, its use in youth with PTSD has not been
      systematically evaluated. We retrospectively examined the tolerability and
      clinical outcomes associated with prazosin treatment in youth with PTSD-related
      nightmares and dysomnias. METHOD: A retrospective chart review identified youth
      with PTSD (N = 40) treated with prazosin between 2014 and 2016 in a trauma
      clinic. We assessed the UCLA PTSD Reaction Index for Diagnostic and Statistical
      Manual of Mental Disorders, Fifth Edition scores (and sub-scores for intrusive,
      hyperarousal, avoidant and negative cognition/mood symptoms) and sleep scale, as
      well as adverse events and vital signs. Linear mixed effects models were utilized
      to evaluate the change in symptom severity, and vital signs were monitored
      throughout treatment. RESULT: Follow-up data were available for 34 patients with
      PTSD (mean age 13.4 +/- 2.9 years, 82% female), of whom 76% had a history of
      sexual abuse and 65% had at least one comorbid psychiatric disorder. The mean
      duration of prazosin treatment was 10.2 +/- 8.1 (range 2-30) weeks, and the mean
      number of follow-up visits was 3 +/- 1.23. Of these 34 patients, 79% received
      trauma-focused cognitive behavioral therapy. The dose range of prazosin was 1-15
      mg at every bedtime (0.02-0.3 mg/kg), with 35% receiving >=5 mg/day. Treatment
      emergent side effects were reported by 26% (n = 8) of patients, including
      dizziness (18%), anxiety (9%) and headaches (6%). Prazosin treatment was
      associated with improved sleep and nightmares over time (pre-treatment 7.3 +/-
      0.9, post-treatment 3.1 +/- 2.4; p < 0.001). CONCLUSION: Prazosin was well
      tolerated and associated with improvements in nightmares and sleep in youth with
      PTSD. Adverse events were consistent with the known side-effect profile of
      prazosin and included dizziness and nausea.

PMID- 28755209
TI  - Storage and Viability Assessment of Date Palm Pollen.
AB  - Pollen storage and viability are very important for pollination, breeding,
      biodiversity, biotechnology, conservation, and other biological and non
      biological studies of the date palm. Optimizing procedures and duration of
      storage are important for effective and long-term date palm pollen storage and
      viability. Here we describe pollen storage methods, such as room temperature (25
      30  degrees C), refrigeration (4  degrees C), storage at 4  degrees C in
      desiccators, deep freezer (-20  degrees C), and cryopreservation (-196  degrees
      C). Based on pollen viability by staining and in vitro germination methods,
      cryopreservation is the best method for long-term storage without any significant
      effect on pollen viability (75-84%); however, the percentage of pollen viability
      depends on the storage period.

PMID- 28755208
TI  - Persistent microglial activation and synaptic loss with behavioral abnormalities
      in mouse offspring exposed to CASPR2-antibodies in utero.
AB  - Gestational transfer of maternal antibodies against fetal neuronal proteins may
      be relevant to some neurodevelopmental disorders, but until recently there were
      no proteins identified. We recently reported a fivefold increase in CASPR2
      antibodies in mid-gestation sera from mothers of children with intellectual and
      motor disabilities. Here, we exposed mice in utero to purified IgG from patients
      with CASPR2-antibodies (CASPR2-IgGs) or from healthy controls (HC-IgGs). CASPR2
      IgG but not HC-IgG bound to fetal brain parenchyma, from which CASPR2-antibodies
      could be eluted. CASPR2-IgG exposed neonates achieved milestones similarly to HC
      IgG exposed controls but, when adult, the CASPR2-IgG exposed progeny showed
      marked social interaction deficits, abnormally located glutamatergic neurons in
      layers V-VI of the somatosensory cortex, a 16% increase in activated microglia,
      and a 15-52% decrease in glutamatergic synapses in layers of the prefrontal and
      somatosensory cortices. Thus, in utero exposure to CASPR2-antibodies led to
      permanent behavioral, cellular, and synaptic abnormalities. These findings
      support a pathogenic role for maternal antibodies in human neurodevelopmental
      conditions, and CASPR2 as a potential target.

PMID- 28755210
TI  - In Vitro Conservation of Date Palm Tissue Cultures.
AB  - In vitro technology offers a potential solution for the conservation of date palm
      germplasm. Slow growth induced by low temperature allows storage from several
      months up to few years. Otherwise, cryopreservation is suitable for long-term in
      vitro conservation, at between -79 and -196  degrees C. This chapter describes a
      protocol for cold storage at 5  degrees C and cryopreservation of date palm
      tissue cultures. For cold storage, 70% of shoot buds remain healthy after storing
      for 12 months at 5  degrees C, and callus cultures remain fully viable after 12
      months of storage. For cryopreservation of embryogenic cultures using dehydration
      by air, apparently, 20 min air drying is the best for cryopreservation. Among
      different types of sugars used as osmotic agents in pre-culture medium, 1 M
      sucrose is the best for the survival of cryopreserved cultures. However, exposure
      of embryogenic cultures to vitrification solution for 60 min at 0  degrees C
      gives the highest percentage of survival and conversion to plantlets.

PMID- 28755211
TI  - Cryopreservation of Date Palm Pro-Embryonic Masses Using the D Cryo-plate
      Technique.
AB  - In this chapter, we describe a cryopreservation (liquid nitrogen, -196  degrees
      C) protocol developed for long-term storage of date palm pro-embryonic masses
      (PEMs), which uses the recently established D cryo-plate technique. Clumps of
      PEMs (3-5 mm in size) were dissected from PEM cultures and placed on pretreatment
      medium containing 171 g/L sucrose for 3 days. Clumps were placed in the wells of
      aluminum cryo-plates in which they were made to adhere using droplets of 3%
      calcium alginate. PEMs were treated for 20 min with a loading solution containing
      184 g/L glycerol and 136.8 g/L sucrose. They were then dehydrated for 90-120 min
      in the air current of a laminar airflow cabinet and immersed directly in liquid
      nitrogen. For rewarming, the cryo-plates holding the PEMs were immersed for 15
      min in an unloading solution containing 410.4 g/L sucrose. The PEMs were then
      detached from the cryo-plates, placed for 3 days in the dark on posttreatment
      medium containing 102.6 g/L sucrose, and transferred on recovery medium under
      light conditions. Using this protocol, 74.6 and 95.8% recovery were achieved with
      the PEMs of the two cultivars tested, Sukkari and Sultany.

PMID- 28755212
TI  - In Vitro Cryopreservation of Date Palm Caulogenic Meristems.
AB  - Cryopreservation is the technology of choice not only for plant genetic resource
      preservation but also for virus eradication and for the efficient management of
      large-scale micropropagation. In this chapter, we describe three cryopreservation
      protocols (standard vitrification, droplet vitrification, and encapsulation
      vitrification) for date palm highly proliferating meristems that are initiated
      from vitro-cultures using plant growth regulator-free MS medium. The positive
      impact of sucrose preculture and cold hardening treatments on survival rates is
      significant. Regeneration rates obtained with standard vitrification,
      encapsulation-vitrification, and droplet-vitrification protocols can reach 30,
      40, and 70%, respectively. All regenerated plants from non-cryopreserved or
      cryopreserved explants don't show morphological variation by maintaining genetic
      integrity without adverse effect of cryogenic treatment. Cryopreservation of date
      palm vitro-cultures enables commercial tissue culture laboratories to move to
      large-scale propagation from cryopreserved cell lines producing true-to-type
      plants after clonal field-testing trials. When comparing the cost of cryostorage
      and in-field conservation of date palm cultivars, tissue cryopreservation is the
      most cost-effective. Moreover, many of the risks linked to field conservation
      like erosion due to climatic, edaphic, and phytopathologic constraints are
      circumvented.

PMID- 28755213
TI  - In Vitro Conservation of Date Palm Shoot-Tip Explants and Callus Cultures Under
      Minimal Growth Conditions.
AB  - Date palm fruit production has great economic significance for many countries.
      There is a fundamental necessity to conserve valuable date palm germplasm, but
      there are various problems with in vivo and ex situ conservation. In vitro
      storage has several advantages over conventional germplasm conservation methods.
      The in vitro technique offers a developed method of slow-growth storage, which is
      considered as an alternate solution for short- and medium-term storage of date
      palm germplasm under controlled conditions. Minimal growth conditions for
      germplasm conservation are generally achieved by reducing growth rate through
      modification of environmental growing conditions and culture, by using low
      temperatures, and the addition of growth retardants and osmotic agents. This
      chapter describes a protocol for short-term in vitro conservation of date palm
      shoot-tip and callus cultures under slow-growth storage conditions, using sucrose
      as an osmotic agent and abscisic acid (ABA) as a growth retardant at 15  degrees
      C for 12 months.

PMID- 28755214
TI  - In Vitro Conservation of Date Palm Somatic Embryos Using Growth-Retardant
      Conditions.
AB  - In vitro conservation is carried out to maintain disease-free genetic materials,
      in a small area, protected against pests, insects, soil problems (alkaline,
      acidic, excess salinity, lack of organic matter, too dry, or too wet), climatic
      changes, and high-multiplication potential. A requirement of successful in vitro
      conservation is that the plants can be regenerated into complete plants rapidly
      when desired. The current work describes in vitro propagation and conservation
      techniques employing slow-growth conditions of date palm somatic embryo cultures.
      Clusters of somatic embryos resulting from an indirect micropropagation protocol
      are conserved in MS culture medium supplemented with an osmotic agent (sucrose at
      90 g/L) combined with a growth-retardant hormone (abscisic acid) at 2 mg/L
      incubated at low temperature (18  degrees C) and low light intensity (10
      MUmol/m2/s). The survival and plant recovery rates are recorded after 10 months.
      Date palm somatic embryo clusters can be conserved for up to 10 months without
      subculture with high survival rates. Successfully conserved somatic embryos
      multiply and germinate to regenerate plants with well-developed shoots and roots,
      which survive acclimatization and field transfer.

PMID- 28755215
TI  - Encapsulation of Date Palm Somatic Embryos: Synthetic Seeds.
AB  - Synthetic seed or encapsulated somatic embryos may be used for propagation,
      storage, and exchange of plant germplasm and have many diverse applications in
      date palm cultivation. They have advantages over conventional use of offshoot
      material for germplasm propagation, maintenance, exchange, and transportation.
      This chapter describes a protocol for date palm synthetic seed production by
      encapsulation of somatic embryos with sodium alginate. Among three concentrations
      used, 3% sodium alginate followed by dropping into 2.5% calcium chloride (CaCl2)
      solution shows the best concentration of gel matrix for both maintenance and
      recovery. In addition, storage of the encapsulated date palm somatic embryos at 5
      degrees C improves the survival and conversion into plantlets; otherwise, 20 g/L
      sucrose in the culture medium enhances conversion of the recovered somatic
      embryos to plantlets. This protocol is promising for in vitro conservation and
      international exchange of date palm germplasm.

PMID- 28755216
TI  - Evaluation of Clonal Fidelity of Micropropagated Date Palm by Random Amplified
      Polymorphic DNA (RAPD).
AB  - Date palm is a fruit-bearing tree commonly found in arid and semiarid regions. It
      is a dioecious plant, producing fruit on female plants and a limited number of
      basal offshoots for propagation. To produce large numbers of uniform plantlets,
      tissue culture techniques are required. It is highly advisable to detect genetic
      variation that may occur through micropropagation techniques as it may lead to
      phenotypic alterations. Random amplified polymorphic DNA (RAPD) is a simple and
      PCR-based molecular marker technique which can be employed to check the
      somaclonal variation. Screening of markers requires repeated confirmation of the
      pattern obtained in individual samples.

PMID- 28755217
TI  - Molecular Identification of Fungal Contamination in Date Palm Tissue Cultures.
AB  - Fungal contamination of in vitro cultures of date palm (Phoenix dactylifera L.)
      is the major constraint to their initiation and maintenance. Different molecular
      approaches have been applied successfully to analyze both inter- and
      intraspecific variation among fungal species as well as determine their identity.
      This chapter describes step-by-step procedures of molecular identification of
      fungal contaminants by internal transcribed spacer (ITS) products of the most
      common fungal contaminants of date palm tissue culture. To begin with, samples of
      genera Alternaria, Aspergillus, Cladosporium, Epicoccum, and Penicillium were
      collected to isolate each fungal genus and extraction of genomic DNA. Polymerase
      chain reactions were accomplished by ITS primers (ITS1 and ITS4) for each fungal
      contaminant as well as for sequencing. Subsequently, they are analyzed by Basic
      Local Alignment Search Tool (BLAST) search of ITS sequence to reveal the identity
      of each individual fungal contaminant species. The molecular identification
      herein is a rapid and reliable procedure to identify date palm fungal
      contaminants which is very important in their control and treatment.

PMID- 28755218
TI  - Genetic Diversity Analysis of Date Palm Using Random Amplified Polymorphic DNA
      (RAPD) and Inter-Simple Sequence Repeat (ISSR).
AB  - Random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR)
      are PCR-based molecular techniques used for evaluation and characterization of
      date palm to find the best genotype and male/female identification at an early
      stage. Genetic fingerprinting using molecular markers is an important tool for
      the analysis of genetic diversity and cultivar identification. Here, we present
      an improved DNA extraction protocol using leaf tissue, based on the standard
      cetyltrimethyl ammonium bromide (CTAB) protocol, which yields large amounts of
      high-quality amplifiable DNA. RAPD and ISSR markers reveal sufficient genetic
      diversity as well as give some unique markers in some genotypes with a maximum
      number of bands.

PMID- 28755219
TI  - Date Palm Genetic Diversity Analysis Using Microsatellite Polymorphism.
AB  - Date palm (Phoenix dactylifera L.) is considered one of the great socioeconomic
      resources in the Middle East and the Arab regions. The tree has been and still is
      at the center of the comprehensive agricultural development. The number of known
      date palm cultivars, distributed worldwide, is approximately 3000. The success of
      genetic diversity conservation or any breeding program depends on an
      understanding of the amount and distribution of the genetic variation already in
      existence in the genetic pool. Development of suitable DNA molecular markers for
      this tree may allow researchers to estimate genetic diversity, which will
      ultimately lead to the genetic conservation of date palm. Simple sequence repeats
      (SSRs) are DNA strands, consisting of tandemly repeated mono-, di-, tri-, tetra-,
      or penta-nucleotide units that are arranged throughout the genomes of most
      eukaryotic species. Microsatellite markers, developed from genomic libraries,
      belong to either the transcribed region or the non-transcribed region of the
      genome, and there is rarely available information on their functions.
      Microsatellite sequences are especially suited to distinguish closely related
      genotypes due to a high degree of variability making them ideally suitable in
      population studies and the identification of closely related cultivars. This
      chapter focuses on the methods employed to characterize date palm genotypes using
      SSR markers.

PMID- 28755220
TI  - Assessing Date Palm Genetic Diversity Using Different Molecular Markers.
AB  - Molecular marker technologies which rely on DNA analysis provide powerful tools
      to assess biodiversity at different levels, i.e., among and within species. A
      range of different molecular marker techniques have been developed and
      extensively applied for detecting variability in date palm at the DNA level.
      Recently, the employment of gene-targeting molecular marker approaches to study
      biodiversity and genetic variations in many plant species has increased the
      attention of researchers interested in date palm to carry out phylogenetic
      studies using these novel marker systems. Molecular markers are good indicators
      of genetic distances among accessions, because DNA-based markers are neutral in
      the face of selection. Here we describe the employment of multidisciplinary
      molecular marker approaches: amplified fragment length polymorphism (AFLP), start
      codon targeted (SCoT) polymorphism, conserved DNA-derived polymorphism (CDDP),
      intron-targeted amplified polymorphism (ITAP), simple sequence repeats (SSR), and
      random amplified polymorphic DNA (RAPD) to assess genetic diversity in date palm.

PMID- 28755221
TI  - Molecular Analysis of Date Palm Genetic Diversity Using Random Amplified
      Polymorphic DNA (RAPD) and Inter-Simple Sequence Repeats (ISSRs).
AB  - The date palm is an ancient domesticated plant with great diversity and has been
      cultivated in the Middle East and North Africa for at last 5000 years. Date palm
      cultivars are classified based on the fruit moisture content, as dry, semidry,
      and soft dates. There are a number of biochemical and molecular techniques
      available for characterization of the date palm variation. This chapter focuses
      on the DNA-based markers random amplified polymorphic DNA (RAPD) and inter-simple
      sequence repeats (ISSR) techniques, in addition to biochemical markers based on
      isozyme analysis. These techniques coupled with appropriate statistical tools
      proved useful for determining phylogenetic relationships among date palm
      cultivars and provide information resources for date palm gene banks.

PMID- 28755222
TI  - Determining Phylogenetic Relationships Among Date Palm Cultivars Using Random
      Amplified Polymorphic DNA (RAPD) and Inter-Simple Sequence Repeat (ISSR) Markers.
AB  - Investigation of genetic variation and phylogenetic relationships among date palm
      (Phoenix dactylifera L.) cultivars is useful for their conservation and genetic
      improvement. Various molecular markers such as restriction fragment length
      polymorphisms (RFLPs), simple sequence repeat (SSR), representational difference
      analysis (RDA), and amplified fragment length polymorphism (AFLP) have been
      developed to molecularly characterize date palm cultivars. PCR-based markers
      random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR)
      are powerful tools to determine the relatedness of date palm cultivars that are
      difficult to distinguish morphologically. In this chapter, the principles,
      materials, and methods of RAPD and ISSR techniques are presented. Analysis of
      data generated from these two techniques and the use of these data to reveal
      phylogenetic relationships among date palm cultivars are also discussed.

PMID- 28755223
TI  - Genotyping and Molecular Identification of Date Palm Cultivars Using Inter-Simple
      Sequence Repeat (ISSR) Markers.
AB  - Molecular markers are credible for the discrimination of genotypes and estimation
      of the extent of genetic diversity and relatedness in a set of genotypes. Inter
      simple sequence repeat (ISSR) markers rapidly reveal high polymorphic
      fingerprints and have been used frequently to determine the genetic diversity
      among date palm cultivars. This chapter describes the application of ISSR markers
      for genotyping of date palm cultivars. The application involves extraction of
      genomic DNA from the target cultivars with reliable quality and quantity.
      Subsequently the extracted DNA serves as a template for amplification of genomic
      regions flanked by inverted simple sequence repeats using a single primer. The
      similarity of each pair of samples is measured by calculating the number of mono-
      and polymorphic bands revealed by gel electrophoresis. Matrices constructed for
      similarity and genetic distance are used to build a phylogenetic tree and cluster
      analysis, to determine the molecular relatedness of cultivars. The protocol
      describes 3 out of 9 tested primers consistently amplified 31 loci in 6 date palm
      cultivars, with 28 polymorphic loci.

PMID- 28755224
TI  - Molecular Identification of Date Palm Cultivars Using Random Amplified
      Polymorphic DNA (RAPD) Markers.
AB  - Ambiguity in the total number of date palm cultivars across the world is pointing
      toward the necessity for an enumerative study using standard morphological and
      molecular markers. Among molecular markers, DNA markers are more suitable and
      ubiquitous to most applications. They are highly polymorphic in nature,
      frequently occurring in genomes, easy to access, and highly reproducible. Various
      molecular markers such as restriction fragment length polymorphism (RFLP),
      amplified fragment length polymorphism (AFLP), simple sequence repeats (SSR),
      inter-simple sequence repeats (ISSR), and random amplified polymorphic DNA (RAPD)
      markers have been successfully used as efficient tools for analysis of genetic
      variation in date palm. This chapter explains a stepwise protocol for extracting
      total genomic DNA from date palm leaves. A user-friendly protocol for RAPD
      analysis and a table showing the primers used in different molecular techniques
      that produce polymorphisms in date palm are also provided.

PMID- 28755225
TI  - Early Sex Identification in Date Palm by Male-Specific Sequence-Characterized
      Amplified Region (SCAR) Markers.
AB  - Date palm (Phoenix dactylifera L.) is a dioecious plant, and sex of the seedlings
      can be determined only at the time of first flowering which takes 4-5 years.
      Female date palm plants are of economic importance as they bear the fruit.
      Therefore, sex identification at an early stage is highly desirable. DNA-based
      markers are useful for early sex detection. In this chapter, we describe male
      specific sequence-characterized amplified region (SCAR) markers to identify sex
      in date palm at the seedling stage. Genomic DNA is isolated separately from both
      male and female date palm genotypes. Amplification of this genomic DNA isolated
      from male and female plants using the SCAR primers results in an amplicon of 406
      bp in both female and male samples and a unique amplicon of 354 bp only in male
      samples. Based on this amplification pattern, the sex of date palm seedlings can
      be predicted.

PMID- 28755226
TI  - Gender Identification in Date Palm Using Molecular Markers.
AB  - Breeding of date palm is complicated because of its long life cycle and
      heterozygous nature. Sexual propagation of date palm does not produce true-to
      type plants. Sex of date palms cannot be identified until the first flowering
      stage. Molecular markers such as random amplified polymorphic DNA (RAPD),
      sequence-characterized amplified regions (SCAR), and simple sequence repeats
      (SSR) have successfully been used to identify the sex-linked loci in the plant
      genome and to isolate the corresponding genes. This chapter highlights the use of
      three molecular markers including RAPD, SCAR, and SSR to identify the gender of
      date palm seedlings.

PMID- 28755227
TI  - Development of Sex-Specific PCR-Based Markers in Date Palm.
AB  - Molecular markers are used efficiently in the development and identification of
      gender-specific PCR-based markers in date palm. There is mounting evidence that
      different marker systems vary in their mechanisms of detecting polymorphism and
      genome coverage. Therefore, they could complement each other to generate accurate
      sex-specific markers in date palm. This chapter describes the uses of PCR-based
      molecular markers to develop and identify the gender in different date palm
      genotypes; these are amplified fragment length polymorphism (AFLP), start codon
      targeted polymorphism (SCoT), conserved DNA-derived polymorphism (CDDP), intron
      targeted amplified polymorphism (ITAP), and random amplified polymorphic DNA
      (RAPD). Also described is how to characterize the identified markers by Sanger
      sequencing and to explore their functions through alignment of their sequences
      with the Genbank databases.

PMID- 28755228
TI  - Date Palm Sex Differentiation Based on Fluorescence In Situ Hybridization (FISH).
AB  - In situ hybridization (ISH) is used to visualize defined DNA sequences in
      cellular preparations by hybridization of complementary probe sequences.
      Recently, the fluorescence in situ hybridization (FISH) technique has become a
      powerful and useful tool for the direct detection of specific DNA fragments in
      the genome. Ribosomal DNA genes (45S and 5S rDNA) are commonly used as markers
      for the physical mapping of plant chromosomes to analyze genomic organization.
      Here we describe cytological-based markers to differentiate date palm gender
      through localization of 45S and 5S rDNA markers on date palm chromosomes using
      FISH.

PMID- 28755229
TI  - Characterization and Amplification of Gene-Based Simple Sequence Repeat (SSR)
      Markers in Date Palm.
AB  - The paucity of molecular markers limits the application of genetic and genomic
      research in date palm (Phoenix dactylifera L.). Availability of expressed
      sequence tag (EST) sequences in date palm may provide a good resource for
      developing gene-based markers. This study characterizes a substantial fraction of
      transcriptome sequences containing simple sequence repeats (SSRs) from the EST
      sequences in date palm. The EST sequences studied are mainly homologous to those
      of Elaeis guineensis and Musa acuminata. A total of 911 gene-based SSR markers,
      characterized with functional annotations, have provided a useful basis not only
      for discovering candidate genes and understanding genetic basis of traits of
      interest but also for developing genetic and genomic tools for molecular research
      in date palm, such as diversity study, quantitative trait locus (QTL) mapping,
      and molecular breeding. The procedures of DNA extraction, polymerase chain
      reaction (PCR) amplification of these gene-based SSR markers, and gel
      electrophoresis of PCR products are described in this chapter.

PMID- 28755230
TI  - Mitochondrial Molecular Markers for Resistance to Bayoud Disease in Date Palm.
AB  - Bayoud disease, caused by Fusarium oxysporum f. sp. albedinis, is a very serious
      and destructive disease to date palm. Screening of date palm germplasm for
      resistance to bayoud disease is a crucial step to avoid or alleviate the disease
      consequences. Fortunately, it was discovered that there are two mitochondrial
      plasmid-like DNA molecules associated with susceptibility or resistance to bayoud
      disease. In this chapter, we present a fast, simple, and reliable technique to
      screen date palm germplasm for the presence of these mitochondrial molecular
      markers associated with susceptibility or resistance to bayoud.

PMID- 28755231
TI  - Analysis of Expressed Sequence Tags (EST) in Date Palm.
AB  - Expressed sequence tags (EST) were generated from a normalized cDNA library of
      the date palm Sukkari cv. to understand the high-quality and better field
      performance of this well-known commercial cultivar. A total of 6943 high-quality
      ESTs were generated, out of them 6671 are submitted to the GenBank dbEST
      (LIBEST_028537). The generated ESTs were assembled into 6362 unigenes, consisting
      of 494 (14.4%) contigs and 5868 (84.53%) singletons. The functional annotation
      shows that the majority of the ESTs are associated with binding (44%), catalytic
      (40%), transporter (5%), and structural molecular (5%) activities. The blastx
      results show that 73% of unigenes are significantly similar to known plant genes
      and 27% are novel. The latter could be of particular interest in date palm
      genetic studies. Further analysis shows that some ESTs are categorized as
      stress/defense- and fruit development-related genes. These newly generated ESTs
      could significantly enhance date palm EST databases in the public domain and are
      available to scientists and researchers across the globe. This knowledge will
      facilitate the discovery of candidate genes that govern important developmental
      and agronomical traits in date palm. It will provide important resources for
      developing genetic tools, comparative genomics, and genome evolution among date
      palm cultivars.

PMID- 28755232
TI  - Development of Genomic Simple Sequence Repeats (SSR) by Enrichment Libraries in
      Date Palm.
AB  - Development of highly informative markers such as simple sequence repeats (SSR)
      for cultivar identification and germplasm characterization and management is
      essential for date palms genetic studies. The present study documents the
      development of SSR markers and assesses genetic relationships of commonly grown
      date palm (Phoenix dactylifera L.) cultivars in different geographical regions of
      Saudi Arabia. A total of 93 novel simple sequence repeat (SSR) markers were
      screened for their ability to detect polymorphism in date palm. Around 71% of
      genomic SSRs are dinucleotide, 25% trinucleotide, 3% tetranucleotide, and 1%
      pentanucleotide motives and show 100% polymorphism. The Unweighted Pair Group
      Method with Arithmetic Mean (UPGMA) cluster analysis illustrates that cultivars
      trend to group according to their class of maturity, region of cultivation, and
      fruit color. Analysis of molecular variations (AMOVA) reveals genetic variation
      among and within cultivars of 27% and 73%, respectively, according to the
      geographical distribution of the cultivars. Developed microsatellite markers are
      of additional value to date palm characterization, tools which can be used by
      researchers in population genetics, cultivar identification, as well as genetic
      resource exploration and management. The cultivars tested exhibited a significant
      amount of genetic diversity and could be suitable for successful breeding
      programs. Genomic sequences generated from this study are available at the
      National Center for Biotechnology Information (NCBI), Sequence Read Archive
      (Accession numbers. LIBGSS_039019).

PMID- 28755233
TI  - MicroRNA Expression in Multistage Date Fruit Development.
AB  - MicroRNAs (miRNAs) are small endogenous noncoding RNAs. Plant miRNAs are known to
      play important regulatory roles in homeostasis, stress response, and diverse
      developmental processes. Here, we describe the identification of conserved miRNAs
      in date palm (Phoenix dactylifera L.) based on transcriptomic data acquired
      across multistage fruit development and genome sequences, which include 238 plant
      conserved miRNAs and 276 novel P. dactylifera-specific miRNAs.

PMID- 28755234
TI  - Proteome of Abiotic Stress Tolerance in Date Palm.
AB  - This protocol describes the analysis of date palm proteome under salinity and
      drought stress conditions to possibly identify proteins involved in stress
      tolerance. Three-month-old date palm seedlings are subjected to drought (27.5 g/L
      polyethylene glycol 6000) and salinity stress conditions (16 g/L NaCl) for 1
      month prior to leaf sample analysis. Differential in gel electrophoresis (DIGE)
      analysis of protein extracts identifies the sensitive proteins that respond to
      abiotic stress. Mass spectrometric analysis identifies the significantly changed
      proteins under both salt and drought stress. This chapter provides techniques for
      analyzing the proteome of date palm under salinity and drought stress.

PMID- 28755235
TI  - Electrophoresis-Based Proteomics to Study Development and Germination of Date
      Palm Zygotic Embryos.
AB  - Proteomics has become an important and powerful tool in plant biology research.
      To establish a proteomic reference map of date palm zygotic embryos (ZE), we
      separated and identified proteins from zygotic embryos during different
      developmental and germination phases using one, two-dimensional polyacrylamide
      gel electrophoresis and mass spectrometry. Proteins are extracted with
      trichloroacetic acid (TCA)/acetone-phenol and resolved by gel electrophoresis.
      Gel images are captured and analyzed by appropriate software and statistical
      packages. Quantitative or qualitative variable bands or spots are subjected to MS
      analysis in order to identify them and correlate differences in the protein
      profiles with the different stages of date palm zygotic embryo development,
      maturation, and germination.

PMID- 28755236
TI  - Date Fruit Proteomics During Development and Ripening Stages.
AB  - Gel-based comparative proteomics approach is a valuable technique for studying
      the changes in abundance of proteins in any given system. The combination of this
      technique with mass spectrometry has provided immense insight into protein
      dynamics during fruit development and ripening. This chapter describes,
      informatively, the procedures for carrying out comparative proteomics analysis of
      date palm (Phoenix dactylifera L.) fruits at different developmental stages using
      a combination of two-dimensional gel electrophoresis (2-DE) and mass
      spectrometry. A comparative proteomics approach provides an overview of protein
      abundances during fruit maturation and insights into proteins that play key roles
      during fruit maturation. Moreover, 2-DE technique enables the visualization of
      total protein distribution and abundance in addition to providing a comparative
      platform following separation of complex proteins based on their molecular weight
      and isoelectric point. Overall, this chapter describes methodologies for
      extraction of proteins from a high carbohydrate-containing fruit, protein quality
      assessment using one-dimensional gel electrophoresis (1-DE), separation using 2
      DE, comparative analysis using Delta2D v4.6, processing of spots of interest, and
      protein identification using mass spectrometry. This protocol is important for
      studies aiming at comparative proteomics to gain insights into changes of protein
      abundances in tissues and organs in general and date palm fruits, in particular.

PMID- 28755237
TI  - Uncertainty quantification and sensitivity analysis of an arterial wall mechanics
      model for evaluation of vascular drug therapies.
AB  - Quantification of the uncertainty in constitutive model predictions describing
      arterial wall mechanics is vital towards non-invasive assessment of vascular drug
      therapies. Therefore, we perform uncertainty quantification to determine
      uncertainty in mechanical characteristics describing the vessel wall response
      upon loading. Furthermore, a global variance-based sensitivity analysis is
      performed to pinpoint measurements that are most rewarding to be measured more
      precisely. We used previously published carotid diameter-pressure and intima
      media thickness (IMT) data (measured in triplicate), and Holzapfel-Gasser-Ogden
      models. A virtual data set containing 5000 diastolic and systolic diameter
      pressure points, and IMT values was generated by adding measurement error to the
      average of the measured data. The model was fitted to single-exponential curves
      calculated from the data, obtaining distributions of constitutive parameters and
      constituent load bearing parameters. Additionally, we (1) simulated vascular drug
      treatment to assess the relevance of model uncertainty and (2) evaluated how
      increasing the number of measurement repetitions influences model uncertainty. We
      found substantial uncertainty in constitutive parameters. Simulating vascular
      drug treatment predicted a 6% point reduction in collagen load bearing ([Formula:
      see text]), approximately 50% of its uncertainty. Sensitivity analysis indicated
      that the uncertainty in [Formula: see text] was primarily caused by noise in
      distension and IMT measurements. Spread in [Formula: see text] could be decreased
      by 50% when increasing the number of measurement repetitions from 3 to 10. Model
      uncertainty, notably that in [Formula: see text], could conceal effects of
      vascular drug therapy. However, this uncertainty could be reduced by increasing
      the number of measurement repetitions of distension and wall thickness
      measurements used for model parameterisation.

PMID- 28755238
TI  - Dissociating the capture of attention from saccade activation by subliminal
      abrupt onsets.
AB  - Attentional capture and effects on saccade metrics by subliminal abrupt onset
      cues have been studied with peripheral cues at one out of several (two to four)
      display locations, swiftly followed by additional onsets at the other display
      locations. The lead time of the cue was too short to be seen. Here, we were
      interested in whether such subliminal onset cues influenced saccades primarily by
      way of attention or by way of direct saccade activation. In separate blocks,
      participants made speeded pro-saccades towards a black target or anti-saccades
      away from the target. Prior to the targets, an abrupt onset cue was presented
      either at the same side as the target (valid condition) or at the opposite side
      (invalid condition). If cues influenced performance by way of attentional
      capture, we expected facilitation of target processing in valid compared to
      invalid conditions (cueing effect) in the pro- as well as in the anti-saccade
      task. If the cues activated saccades in their direction, we expected the cueing
      effect to drop in the anti-saccade task compared to the pro-saccade task because
      in the anti-saccade task the invalid cue would activate the finally required
      response, whereas the valid cue would activate the alternative response, leading
      to interference. Results were in line with the former of these possibilities
      suggesting that subliminal abrupt onsets influenced saccades by way of attention
      with no or little direct activation of saccades.

PMID- 28755239
TI  - Prism adaptation speeds reach initiation in the direction of the prism after
      effect.
AB  - Damage to the temporal-parietal cortex in the right hemisphere often leads to
      spatial neglect-a disorder in which patients are unable to attend to sensory
      input from their contralesional (left) side. Neglect has been associated with
      both attentional and premotor deficits. That is, in addition to having difficulty
      with attending to the left side, patients are often slower to initiate leftward
      vs. rightward movements (i.e., directional hypokinesia). Previous research has
      indicated that a brief period of adaptation to rightward shifting prisms can
      reduce symptoms of neglect by adjusting the patient's movements leftward, toward
      the neglected field. Although prism adaptation has been shown to reduce spatial
      attention deficits in patients with neglect, very little work has examined the
      effects of prisms on premotor symptoms. In the current study, we examined this in
      healthy individuals using leftward shifting prisms to induce a rightward shift in
      the egocentric reference frame, similar to neglect patients prior to prism
      adaptation. Specifically, we examined the speed with which healthy participants
      initiated leftward and rightward reaches (without visual feedback) prior to and
      following adaptation to either 17 degrees  leftward (n = 16) or 17 degrees 
      rightward (n = 15) shifting prisms. Our results indicated that, following
      adaptation, participants were significantly faster to initiate reaches towards
      targets located in the direction opposite the prism shift. That is, participants
      were faster to initiate reaches to right targets following leftward prism
      adaptation and were faster to initiate reaches to left targets following
      rightward prism adaptation. Overall, these results are consistent with the idea
      that prism adaptation can influence the speed with which a reach can be initiated
      toward a target in the direction opposite the prism shift, possibly through
      altering activity in neural circuits involved in reach planning.

PMID- 28755240
TI  - Bridging to liver transplantation in HCC patients.
AB  - BACKGROUND: Liver transplantation (LT) is the only cure for patients diagnosed
      with unresectable hepatocellular carcinoma (HCC), and HCC has become the leading
      indication for LT in the USA. The shortage of liver grafts results in a
      significant waiting time for LT with the risk of tumour progression. Treating
      HCCs during the waiting time prior to transplantation (bridging therapy) is an
      attractive strategy to reduce the risk of exceeding the tumour criteria for
      transplantation. Studies on bridging therapy are heterogenous and due to ethical
      issues, mostly of retrospective design. PURPOSE: We summarize the main studies
      and methods that have been reported on bridging therapies for patients with HCC
      waiting for a LT. CONCLUSION: During the waiting period for LT, patients with HCC
      at risk for tumour progression and therefore bridging therapy is recommended for
      patients with an estimated waiting time of >=6 months. Bridging therapy for
      patients with HCC prior to LT mainly include locoregional therapies (LRTs), with
      transarterial chemoembolization (TACE) being the most common, followed by radio
      frequency ablation (RFA). Because of a continuous enhancement of therapy options,
      including a more precise adjustment of external radiotherapy, further
      possibilities for an individualized bridging therapy for patients with HCC have
      been developed. Patients with compensated liver cirrhosis and small tumour size
      are preferably treated with RFA, whereas patients with larger tumour size but
      compensated liver function are treated with TACE/TARE. Patients with
      uncompensated liver cirrhosis and larger tumour size can nowadays be successfully
      bridged to LT with external radiotherapy without increasing the risk for further
      deterioration of liver function.

PMID- 28755241
TI  - Therapeutic radiation for lymphoma and risk of second primary malignant
      mesothelioma.
AB  - PURPOSE: This large, population-based U.S. study of lymphoma patients followed
      for up to four decades enables detailed analysis of second primary mesothelioma
      risk after radiotherapy. METHODS: U.S. Surveillance, Epidemiology, and End
      Results data were used to identify second primary mesothelioma among patients
      diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) between 1973
      and 2014. Standardized incidence ratios (SIRs) were calculated by radiotherapy.
      Multivariate adjusted associations were examined using competing risks survival
      analysis. RESULTS: Among 47,219 HL patients (19,538 irradiated) and 252,090 NHL
      patients (52,454 irradiated), second primary mesothelioma developed among 28
      lymphoma patients who received radiotherapy and 59 who did not. Mesothelioma risk
      was increased among HL and NHL patients treated with radiotherapy [SIR = 1.78,
      95% confidence interval (CI) 1.18-2.58], but not without radiotherapy. After
      multivariate adjustment, radiotherapy was associated with increased mesothelioma
      risk (relative risk = 1.64, 95% CI 1.05-2.57), especially in lymphoma patients
      diagnosed before 1995 and after a latency of at least 10 years, and apparently
      with younger age at diagnosis. CONCLUSIONS: The increase in second primary
      mesothelioma risk following radiotherapy for lymphoma is independent of several
      patient and disease characteristics, and is higher with earlier treatment era and
      longer latency.

PMID- 28755242
TI  - Emergency surgery for colorectal cancer does not affect nodal harvest comparing
      elective procedures: a propensity score-matched analysis.
AB  - PURPOSE: About 30% of colorectal cancers (CRCs) present with acute symptoms. The
      adequacy of oncologic resections is a matter of concern since few authors
      reported that emergency surgery in these patients results in a lower lymph node
      harvest (LNH). In addition, emergency resections have been reported with a longer
      hospital stay and higher morbidity rate. We thus conducted a propensity score
      matched analysis with the aim of investigating LNH in emergency specimens
      comparing with elective ones. Secondary aim was the comparison of morbidity and
      hospital stay. METHODS: Eighty-seven consecutive R0 emergency surgical procedures
      were matched with elective CRCs using the propensity score method and the
      following covariates: age, sex, stage, and localization. Groups were compared
      using univariate and multivariate analyses. Outcome measures were LNH, nodal
      ratio, Clavien's morbidity grades, and hospital stay. RESULTS: Emergency patients
      presented more metastatic nodes compared with elective ones (p 0.017); however,
      both presented a comparable mean LNH. Multivariate analysis documented that a T
      stage >=3 was the only variable correlated with a nodal positivity (OR 6.3). On
      univariate analysis, emergency CRCs had a longer mean hospital stay compared with
      elective resections (p 0.006) and a higher rate of Clavien >=4 events (p 0.0173).
      Finally, emergency resection and an age >66 years were variables independently
      correlated with a mean hospital stay >10 days (OR, respectively, 3.7 and 3.5).
      CONCLUSIONS: Emergency CRC resections were equivalent to the elective procedures
      with respect to LNH. However, emergency surgery correlated with a longer mean
      hospital stay. Graphical abstract Emergency and Elective resections for CRC
      provide similar LNH.

PMID- 28755243
TI  - Treatment of transsphincteric fistula-in-ano with growth factors from autologous
      platelets: results of a phase II clinical trial.
AB  - PURPOSE: The aim of this paper is to evaluate to the safety, feasibility and
      efficacy of a novel treatment for transsphincteric cryptoglandular fistula:
      injection of autologous plasma rich in growth factors (PRGF) into the fistula
      tract accompanied by sealing using a fibrin plug created from the activated
      platelet-poor fraction of the same plasma. METHOD: This article is a prospective,
      phase II clinical trial. The procedure was externally audited. Thirty-six
      patients diagnosed with transsphincteric fistula-in-ano were included. All
      patients underwent follow-up examinations at 1 week and again at 3, 6 and 12
      months after discharge. Main outcome measures safety (number of adverse events),
      feasibility and effectiveness of the treatment. RESULTS: A total of 36 patients
      received the study treatment, with the procedure found to be feasible in all
      patients. A total of seven adverse events (AE) related to the injected product or
      surgical procedure were identified in 4 of 36 patients. At the end of the follow
      up period (12 months), 33.3% of patients (12/36) had achieved complete fistula
      healing and 11.1% of patients (4/36) had achieved partial healing. In total, this
      amounted to 44.4% of patients (16/36) being asymptomatic at final follow-up. In
      successfully healed patients, a gradual reduction in pain was observed, as
      measured using a Visual Analog Scale (VAS) (p = 0.0278). Compared to baseline, a
      significant improvement in Wexner score was seen in patients achieving total or
      partial healing of the fistula (p = 0.0195). CONCLUSIONS: The study treatment was
      safe and feasible, with apparently modest efficacy rates. Continence and pain
      improvement following treatment may be considered predictive factors for healing.

PMID- 28755244
TI  - A Brief Smoking Cessation Advice by Youth Counselors for the Smokers in the Hong
      Kong Quit to Win Contest 2010: a Cluster Randomized Controlled Trial.
AB  - Smoking cessation counseling by healthcare professionals is effective, but very
      few healthcare professionals can deliver these interventions in the busy clinical
      settings. This study aimed to evaluate the effectiveness of a brief smoking
      cessation advice delivered by briefly-trained youth counselors at the enrolment
      of an incentive-based smoking cessation campaign. The study design was a cluster
      2-arm randomized controlled trial of 831 Chinese adult smokers who were recruited
      in public areas to participate in the Hong Kong Quit to Win Contest 2010. The
      intervention group (n = 441) received a 5-min quitting advice from the youth
      counselors, who were mainly undergraduate nursing students, and a 12-page self
      help smoking cessation booklet at the enrolment, while the control group (n =
      390) only received the same booklet. Biochemically confirmed quitters at 6-month
      follow-up could join a lucky draw that offered HK$10,000 (US$1282) cash prize to
      three winners and HK$4000 gift vouchers to the other 10 winners. Primary outcome
      was self-reported smoking abstinence at 6-month follow-up. By intention-to-treat,
      the intervention group had a non-significantly higher self-reported (18.4 versus
      13.8%, OR = 1.40, 95% CI 0.96-2.04, p = 0.08) and validated quit rate (9.1 versus
      6.7%, OR = 1.40, 95% CI 0.84-2.33, p = 0.20) than the control group at 6-month
      follow-up. The analysis with multiple imputation for missing data also found
      similar results. We concluded that the brief on-site advice by trained youth
      counselors had a modest effect on smoking cessation, but the effect was not
      significant. Future studies with larger sample size and results from higher
      participation of the biochemical validation to confirm the effectiveness are
      warranted.

PMID- 28755245
TI  - In Silico Analysis of Fatty Acid Desaturase Genes and Proteins in Grasses.
AB  - Fatty acid desaturases (FADs) catalyze the introduction of a double bond into
      acyl chains. Two FAD groups have been identified in plants: acyl-acyl carrier
      proteins (ACPs) and acyl-lipid or membrane-bound FAD. The former catalyze the
      conversion of 18:0 to 18:1 and to date have only been identified in plants. The
      latter are found in eukaryotes and bacteria and are responsible for multiple
      desaturations. In this study, we identified 82 desaturase gene and protein
      sequences from 10 grass species deposited in GenBank that were analyzed using
      bioinformatic approaches. Subcellular localization predictions of desaturase
      family revealed their localization in plasma membranes, chloroplasts, endoplasmic
      reticula, and mitochondria. The in silico mapping showed multiple chromosomal
      locations in most species. Furthermore, the presence of the characteristic
      histidine domains, the predicted motifs, and the finding of transmembrane regions
      strongly support the protein functionality. The identification of putative
      regulatory sites in the promotor and the expression profiles revealed the wide
      range of pathways in which fatty acid desaturases are involved. This study is an
      updated survey on desaturases of grasses that provides a comprehensive insight
      into diversity and evolution. This characterization is a necessary first step
      before considering these genes as candidates for new biotechnological approaches.

PMID- 28755246
TI  - Biocatalytic Asymmetric Synthesis of (1R, 2S)-N-Boc-vinyl-ACCA Ethyl Ester with a
      Newly Isolated Sphingomonas aquatilis.
AB  - 1-amino cyclopropane-1-carboxylic acid (ACCA) and its derivatives are essential
      pharmacophoric unit that widely used in drug research and development.
      Specifically, (1R, 2S)-N-Boc-vinyl-ACCA ethyl ester (vinyl-ACCA) is a key chiral
      intermediate in the synthesis of highly potent hepatitis C virus (HCV) NS3/4A
      protease inhibitors such as asunaprevir and simeprevir. Developing strategies for
      the asymmetric synthesis of vinyl-ACCA is thus extremely high demand. In this
      study, 378 bacterial strains were isolated from soil samples using N-Boc-vinyl
      ACCA ethyl ester as the sole carbon source and were screened for esterase
      activity. Fourteen of which worked effectively for the asymmetric synthesis of
      (1R, 2S)-N-Boc-1-vinyl ACCA ethyl ester. The strain CY-2, identified as
      Sphingomonas aquatilis, which showed the highest stability and enantioselectivity
      was selected as whole cell biocatalyst for further study. A systematic study of
      all factors influencing the enzymatic hydrolysis was performed. Under optimized
      conditions, resolution of rac-vinyl-ACCA to (1R, 2S)-N-Boc-1-vinyl ACCA ethyl
      ester with 88.2% ee and 62.4% conversion (E = 9) was achieved. Besides, S.
      aquatilis was also used to transform other 10 different substrates. Notably, it
      was found that 7 of them could be stereoselectively hydrolyzed, especially for
      (1R,2S)-1-amino-vinyl-ACCA ethyl ester hydrochloride (99.6% ee, E>200). Our
      investigations provide a new efficient whole cell biocatalyst for resolution of
      ACCA and might be developed for industry application.

PMID- 28755247
TI  - An Online Drug Abuse Prevention Program for Adolescent Girls: Posttest and 1-Year
      Outcomes.
AB  - Early adolescent girls' rates of drug use have matched, and in some instances,
      surpassed boys' rates. Though girls and boys share risk factors for drug use,
      girls also have gender-specific risks. Tailored interventions to prevent girls'
      drug use are warranted. This study developed and tested a web-based, drug abuse
      prevention program for adolescent girls. The nationwide sample of 13- and 14-year
      old girls (N = 788) was recruited via Facebook ads. Enrolled girls were randomly
      assigned to the intervention or control condition. All girls completed pretest
      measures online. Following pretest, intervention girls interacted with the 9
      session, gender-specific prevention program online. The program aimed to reduce
      girls' drug use and associated risk factors by improving their cognitive and
      behavioral skills around such areas as coping with stress, managing mood,
      maintaining a healthy body image, and refusing drug use offers. Girls in both
      conditions again completed measures at posttest and 1-year follow-up. At
      posttest, and compared to girls in the control condition, girls who received the
      intervention smoked fewer cigarettes and reported higher self-esteem, goal
      setting, media literacy, and self-efficacy. At 1-year follow-up, and compared to
      girls in the control condition, girls who received the intervention reported
      engaging in less binge drinking and cigarette smoking; girls assigned to the
      intervention condition also had higher alcohol, cigarette, and marijuana refusal
      skills, coping skills, and media literacy and lower rates of peer drug use. This
      study's findings support the use of tailored, online drug abuse prevention
      programming for early adolescent girls.

PMID- 28755249
TI  - Can Locus of Control Compensate for Socioeconomic Adversity in the Transition
      from School to Work?
AB  - Internal locus of control is associated with academic success and indicators of
      wellbeing in youth. There is however less understanding regarding the role of
      locus of control in shaping the transition from school to work beyond the more
      widely studied predictors of socioeconomic background and academic attainment.
      Guided by a socio-ecological model of agency, the current study examines to which
      extent internal locus of control, understood as an indicator of individual
      agency, can compensate for a lack of socioeconomic resources by moderating the
      association between parental disadvantage and difficulties in the transition from
      school to work. We draw on data collected from a longitudinal nationally
      representative cohort of 15,770 English youth (48% female) born in 1989/90,
      following their lives from age 14 to 20. The results suggest that the influence
      of agency is limited to situations where socioeconomic risk is not overpowering.
      While internal locus of control may help to compensate for background
      disadvantage regarding avoidance of economic inactivity and unemployment to some
      extent, it does not provide protection against long-term inactivity, i.e. more
      than 6 months spent not in education, employment or training.

PMID- 28755250
TI  - Mental Health and Educational Experiences Among Black Youth: A Latent Class
      Analysis.
AB  - Disproportionately lower educational achievement, coupled with higher grade
      retention, suspensions, expulsions, and lower school bonding make educational
      success among Black adolescents a major public health concern. Mental health is a
      key developmental factor related to educational outcomes among adolescents;
      however, traditional models of mental health focus on absence of dysfunction as a
      way to conceptualize mental health. The dual-factor model of mental health
      incorporates indicators of both subjective wellbeing and psychopathology,
      supporting more recent research that both are needed to comprehensively assess
      mental health. This study applied the dual-factor model to measure mental health
      using the National Survey of American Life-Adolescent Supplement (NSAL-A), a
      representative cross-sectional survey. The sample included 1170 Black adolescents
      (52% female; mean age 15). Latent class analysis was conducted with positive
      indicators of subjective wellbeing (emotional, psychological, and social) as well
      as measures of psychopathology. Four mental health groups were identified, based
      on having high or low subjective wellbeing and high or low psychopathology.
      Accordingly, associations between mental health groups and educational outcomes
      were investigated. Significant associations were observed in school bonding,
      suspensions, and grade retention, with the positive mental health group (high
      subjective wellbeing, low psychopathology) experiencing more beneficial outcomes.
      The results support a strong association between school bonding and better mental
      health and have implications for a more comprehensive view of mental health in
      interventions targeting improved educational experiences and mental health among
      Black adolescents.

PMID- 28755251
TI  - Appreciating Complexity in Adolescent Self-Harm Risk Factors: Psychological
      Profiling in a Longitudinal Community Sample.
AB  - Past research identifies a number of risk factors for adolescent self-harm, but
      often fails to account for overlap between these factors. This study investigated
      the underlying, broader concepts by identifying different psychological profiles
      among adolescents. We then compared new self-harm rates over a six-month period
      across different psychological profiles. Australian high school students (n =
      326, 68.1% female) completed a questionnaire including a broad range of
      psychological and socioenvironmental risk and protective factors. Non
      hierarchical cluster analysis produced six groups with different psychological
      profiles at baseline and rate of new self-harm at follow-up. The lowest rate was
      1.4% in a group that appeared psychologically healthy; the highest rate was 37.5%
      in a group that displayed numerous psychological difficulties. Four groups with
      average self-harm had varied psychological profiles including low impulsivity,
      anxiety, impulsivity, and poor use of positive coping strategies. Identifying
      multiple profiles with distinct psychological characteristics can improve
      detection, guide prevention, and tailor treatment.

PMID- 28755252
TI  - Perceptions of Relatedness with Classroom Peers Promote Adolescents' Behavioral
      Engagement and Achievement in Secondary School.
AB  - Secondary school is a vulnerable time where stagnation or declines in classroom
      behavioral engagement occur for many students, and peer relationships take on a
      heightened significance. We examined the implications of adolescents' perceptions
      of relatedness with classroom peers for their academic learning. Participants
      were 1084 adolescents (53% female) in 65 middle and high school classrooms.
      Multilevel cross-lagged path analyses found that adolescents' perceived
      relatedness with classroom peers subsequently predicted their increased self
      reported behavioral engagement in that classroom from fall to winter and again
      from winter to spring. Higher engagement in spring predicted higher end of year
      objective achievement test scores after statistical control of prior year test
      scores. Implications are discussed for increasing classroom peer relatedness to
      enhance adolescents' achievement.

PMID- 28755253
TI  - As solid as a rock-comparison of CE- and MPS-based analyses of the petrosal bone
      as a source of DNA for forensic identification of challenging cranial bones.
AB  - Short tandem repeat (STR) typing from skeletal remains can be a difficult task.
      Dependent on the environmental conditions of the provenance of the bones, DNA can
      be degraded and STR typing inhibited. Generally, dense and compact bones are
      known to preserve DNA better. Several studies already proved that femora and
      teeth have high DNA typing success rates. Unfortunately, these elements are not
      present in all cases involving skeletal remains. Processing partial or singular
      skeletal elements, it is favorable to select bone areas where DNA preservation is
      comparably higher. Especially, cranial bones are often accidentally discovered
      during criminal investigations. The cranial bone is composed of multiple parts.
      In this examination, we evaluated the potential of the petrous bone for human
      identification of skeletal remains in forensic case work. Material from different
      sections of eight unknown cranial bones and-where available-additionally other
      skeletal elements, collected at the DNA department of the Institute of Legal
      Medicine in Ulm, Germany, from 2010 to 2017, were processed with an optimized DNA
      extraction and STR typing strategy. The results highlight that STR typing from
      the petrous bones leads to reportable profiles in all individuals, even in cases
      where the analysis of the parietal bone failed. Moreover, the comparison of
      capillary electrophorese (CE) typing to massively parallel sequencing (MPS)
      analysis shows that MPS has the potential to analyze degraded human remains and
      is even capable to provide additional information about phenotype and ancestry of
      unknown individuals.

PMID- 28755254
TI  - Looking for the Good, Bad and the Ugly rectal cancers of the twenty-first
      century... or "How to avoid tears when peeling onions".

PMID- 28755255
TI  - Magnetic resonance defecography versus videodefecography in the study of
      obstructed defecation syndrome: Is videodefecography still the test of choice
      after 50 years?
AB  - BACKGROUND: The aim of the present study was to evaluate the diagnostic accuracy
      of magnetic resonance (MR) defecography and compare it with videodefecography in
      the evaluation of obstructed defecation syndrome. METHODS: This was a prospective
      cohort test accuracy study conducted at one major tertiary referral center on
      patients with a diagnosis of obstructed defecation syndrome who were referred to
      the colorectal surgery clinic in a consecutive series from 2009 to 2012. All
      patients underwent a clinical examination, videodefecography, and MR defecography
      in the supine position. We analyzed diagnostic accuracy for MR defecography and
      performed an agreement analysis using Cohen's kappa index (kappa) for each
      diagnostic imaging examination performed with videodefecography and MR
      defecography. RESULTS: We included 40 patients with Rome III diagnostic criteria
      of obstructed defecation syndrome. The degree of agreement between the two tests
      was as follows: almost perfect for anismus (kappa = 0.88) and rectal prolapse
      (kappa = 0.83), substantial for enterocele (kappa = 0.80) and rectocele grade III
      (kappa = 0.65), moderate for intussusception (kappa = 0.50) and rectocele grade
      II (kappa = 0.49), and slight for rectocele grade I (kappa = 0.30) and excessive
      perineal descent (kappa = 0.22). Eighteen cystoceles and 11 colpoceles were
      diagnosed only by MR defecography. Most patients (54%) stated that
      videodefecography was the more uncomfortable test. CONCLUSIONS: MR defecography
      could become the imaging test of choice for evaluating obstructed defecation
      syndrome.

PMID- 28755256
TI  - Rectal sparing approach after preoperative radio- and/or chemotherapy (RESARCH)
      in patients with rectal cancer: a multicentre observational study.
AB  - BACKGROUND: Rectum-sparing approaches appear to be appropriate in rectal cancer
      patients with a major (mCR) or complete clinical response (cCR) after neoadjuvant
      therapy. The aim of the present study is to evaluate the effectiveness of rectum
      sparing approaches at 2 years after the completion of neoadjuvant treatment.
      STUDY DESIGN: Patients with rectal adenocarcinoma eligible to receive neoadjuvant
      therapy will be prospectively enrolled. Patients will be restaged 7-8 weeks after
      the completion of neoadjuvant therapy and those with mCR (defined as absence of
      mass, small mucosal irregularity no more than 2 cm in diameter at endoscopy and
      no metastatic nodes at MRI) or cCR will be enrolled in the trial. Patients with
      mCR will undergo local excision, while patients with cCR will either undergo
      local excision or watch and wait policy. The main end point of the study is to
      determine the percentage of rectum preservation at 2 years in the enrolled
      patients. CONCLUSION: This protocol is the first prospective trial that
      investigates the role of both local excision and watch and wait approaches in
      patients treated with neoadjuvant therapy for rectal cancer. The trial is
      registered at clinicaltrials.gov (NCT02710812).

PMID- 28755257
TI  - Two-way Interaction Effects of Perioperative Complications on 30-Day Mortality in
      General Surgery.
AB  - BACKGROUND: Multiple perioperative complications increase mortality risk, and
      certain complications synergistically increase this risk to a greater degree than
      might be expected if the complications were independent, but these effects are
      not well established. METHODS: This is a retrospective cohort study of 422,827
      intraabdominal general surgery patients (American College of Surgeons National
      Surgical Quality Improvement Program 2005-2011). Eight complications were
      evaluated: acute respiratory failure (ARF), acute kidney injury (AKI),
      sepsis/septic shock, stroke, cardiac arrest (CA), myocardial infarction (MI),
      deep vein thrombosis/pulmonary embolus, and transfusion. Each combination of two
      complications (28 total) was modeled using a Cox model for 30-day mortality, with
      adjustment for preoperative comorbidities and risk factors. Additive interaction
      was determined with the relative excess risk due to interaction (RERI). A
      positive RERI indicates that the mortality risk with both complications is
      greater than the sum of the individual mortality risks. Bonferroni correction was
      applied (alpha = 0.05/28 = 0.0018). RESULTS: Seven combinations demonstrated
      positive interaction: sepsis-CA (RERI 88.1; p < 0.0001), ARF-AKI (RERI 50.5; p <
      0.0001), AKI-sepsis (RERI 33.9; p < 0.0001), sepsis-stroke (RERI 33.9; p <
      0.0001), ARF-stroke (RERI 32.3; p < 0.0001), AKI-MI (RERI 24.5; p = 0.0013), and
      ARF-sepsis (RERI 19.2; p < 0.0001). Two combinations demonstrated negative
      interaction: ARF-CA (RERI -65.1; p = 0.0017) and CA-transfusion (RERI -52.0, p <
      0.0001). CONCLUSIONS: Interaction effects exist between certain complications to
      increase the risk of short-term mortality. ARF, AKI, sepsis, and stroke were most
      likely to be involved in positive interactions. Further research into the
      mechanisms for these effects will be necessary to develop strategies to minimize
      the compounding effects of multiple complications in the perioperative period.

PMID- 28755258
TI  - Towards High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray
      Ionization Mass Spectrometry Coupled to Shear Force Microscopy.
AB  - Constant mode ambient mass spectrometry imaging (MSI) of tissue sections with
      high lateral resolution of better than 10 MUm was performed by combining shear
      force microscopy with nanospray desorption electrospray ionization (nano-DESI).
      Shear force microscopy enabled precise control of the distance between the sample
      and nano-DESI probe during MSI experiments and provided information on sample
      topography. Proof-of-concept experiments were performed using lung and brain
      tissue sections representing spongy and dense tissues, respectively. Topography
      images obtained using shear force microscopy were comparable to the results
      obtained using contact profilometry over the same region of the tissue section.
      Variations in tissue height were found to be dependent on the tissue type and
      were in the range of 0-5 MUm for lung tissue and 0-3 MUm for brain tissue
      sections. Ion images of phospholipids obtained in this study are in good
      agreement with literature data. Normalization of nano-DESI MSI images to the
      signal of the internal standard added to the extraction solvent allowed us to
      construct high-resolution ion images free of matrix effects. Graphical Abstract
      ?.

PMID- 28755259
TI  - Structural Characterization of a Thrombin-Aptamer Complex by High Resolution
      Native Top-Down Mass Spectrometry.
AB  - Native mass spectrometry (MS) with electrospray ionization (ESI) has evolved as
      an invaluable tool for the characterization of intact native proteins and non
      covalently bound protein complexes. Here we report the structural
      characterization by high resolution native top-down MS of human thrombin and its
      complex with the Bock thrombin binding aptamer (TBA), a 15-nucleotide DNA with
      high specificity and affinity for thrombin. Accurate mass measurements revealed
      that the predominant form of native human alpha-thrombin contains a glycosylation
      mass of 2205 Da, corresponding to a sialylated symmetric biantennary
      oligosaccharide structure without fucosylation. Native MS showed that thrombin
      and TBA predominantly form a 1:1 complex under near physiological conditions (pH
      6.8, 200 mM NH4OAc), but the binding stoichiometry is influenced by the solution
      ionic strength. In 20 mM ammonium acetate solution, up to two TBAs were bound to
      thrombin, whereas increasing the solution ionic strength destabilized the
      thrombin-TBA complex and 1 M NH4OAc nearly completely dissociated the complex.
      This observation is consistent with the mediation of thrombin-aptamer binding
      through electrostatic interactions and it is further consistent with the human
      thrombin structure that contains two anion binding sites on the surface. Electron
      capture dissociation (ECD) top-down MS of the thrombin-TBA complex performed with
      a high resolution 15 Tesla Fourier transform ion cyclotron resonance (FTICR) mass
      spectrometer showed the primary binding site to be at exosite I located near the
      N-terminal sequence of the heavy chain, consistent with crystallographic data.
      High resolution native top-down MS is complementary to traditional structural
      biology methods for structurally characterizing native proteins and protein-DNA
      complexes. Graphical Abstract ?.

PMID- 28755260
TI  - Visible Multiphoton Dissociation of Chromophore-Tagged Peptides.
AB  - The visible photodissociation mechanisms of QSY7-tagged peptides of increasing
      size have been investigated by coupling a mass spectrometer and an optical
      parametric oscillator laser beam. The experiments herein consist of energy
      resolved collision- and laser-induced dissociation measurements on the
      chromophore-tagged peptides. The results show that fragmentation occurs by
      similar channels in both activation methods, but that the branching ratios are
      vastly different. Observation of a size-dependent minimum laser pulse energy
      required to induce fragmentation, and collisional cooling rates in time resolved
      experiments show that laser-induced dissociation occurs through the absorption of
      multiple photons by the chromophore and the subsequent heating through
      vibrational energy redistribution. The differences in branching ratio between
      collision- and laser-induced dissociation can then be understood by the highly
      anisotropic energy distribution following absorption of a photon. Graphical
      Abstract ?.

PMID- 28755261
TI  - Acinetobacter pittii, an emerging new multi-drug resistant fish pathogen isolated
      from diseased blunt snout bream (Megalobrama amblycephala Yih) in China.
AB  - Despite the reason that genus Acinetobacter works as a grave human pathogen, very
      few numbers of researches have been done so that term it as a pathogen in respect
      to fish. As per the current study, isolation of three pathogenic bacterial
      strains was carried out from infected blunt snout bream (Megalobrama amblycephala
      Yih), from a farm in Yixing city, Jiangsu province, China, which displayed
      symptoms like tail-rot, shedding scales and ascites in addition to gentle
      ulceration on the entire body regardless of size and sex of fish. Taking into
      account the bases of morphology, varied biochemical tests, 16S rDNA segment and
      rpoB gene sequence analysis, in addition to phylogenetic study, the pathogenic
      bacteria was identified as A. pittii. Recursive infectivity experiment validated
      their pathogenicity. Pathological modifications of blunt snout bream infected
      with A. pittii were taken into observation. Confirmation of the pathogenicity was
      additionally made by infectivity studies of zebra fish (Brachydanio rerio) and
      nematode (Caenorhabditis elegans). The drug resistance of these isolates was also
      scrutinized. All isolates, recognized as multiple drug resistant strains,
      showcased resistance to clindamycin, streptomycin, vancomycin, cephalosporins,
      ampicillin, piperacillin, and trimethoprim-sulfamethoxazole, while showcasing
      sensitivity to norfloxacin, gentamicin, amikacin, and imipenem. Multi-locus
      sequence typing of these A. pittii isolates brought to light a new clonal lineage
      of Acinetobacter leading to fish septicemia outbreaks together with indicating
      that Acinetobacter stains with the new sequence type 839 may be the dominant
      clone. This is the first report dealing with the infection caused by A. pittii in
      fish that suggests that A. pittii has a prospective threat to be encountered by
      freshwater fish farming in addition to causing human clinical infections.

PMID- 28755262
TI  - Physicochemical and microbial responses of Streptomyces natalensis HW-2 to fungal
      elicitor.
AB  - The effects of fungal elicitor on the physicochemical and microbial responses of
      Streptomyces natalensis HW-2 were investigated. The results showed that the
      elicitor could decrease dry cell weight (DCW) by 17.7% and increase the
      utilization of glucose, while the curve of pH was not obviously altered. The
      elicitor enhanced the yield of natamycin from 1.33 to 2.49 g/L. The morphology of
      the colony and the mycelium treated with elicitor showed significant differences
      from that of control. The level of intracellular reactive oxygen species (ROS)
      increased to 333.8 ng/L, which was a twofold increase comparing with the control.
      The concentration of Ca2+ reached 421.1 nmol/L, which increased by 32.8% after
      the addition of the elicitor. The activities of pyruvic carboxylase and
      phosphoenol pyruvate carboxylase were enhanced by 27.8 and 11.9%, respectively,
      while citrate synthase activity decreased by 23.1% in comparison with the
      control.

PMID- 28755263
TI  - Phage-host associations in a full-scale activated sludge plant during sludge
      bulking.
AB  - Sludge bulking, a notorious microbial issue in activated sludge plants, is always
      accompanied by dramatic changes in the bacterial community. Despite large numbers
      of phages in sludge systems, their responses to sludge bulking and phage-host
      associations during bulking are unknown. In this study, high-throughput
      sequencing of viral metagenomes and bacterial 16S rRNA genes were employed to
      characterize viral and bacterial communities in a sludge plant under different
      sludge conditions (sludge volume index (SVI) of 180, 132, and 73 ml/g). Bulking
      sludges (SVI > 125 ml/g) taken about 10 months apart exhibited similar bacterial
      and viral composition. This reflects ecological resilience of the sludge
      microbial community and indicates that changes in viral and bacterial populations
      correlate closely with each other. Overgrowth of "Candidatus Microthrix
      parvicella" led to filamentous bulking, but few corresponding viral genotypes
      were identified. In contrast, sludge viromes were characterized by numerous
      contigs associated with "Candidatus Accumulibacter phosphatis," suggesting an
      abundance of corresponding phages in the sludge viral community. Notably, while
      nitrifiers (mainly Nitrosomonadaceae and Nitrospiraceae) declined significantly
      along with sludge bulking, their corresponding viral contigs were identified more
      frequently and with greater abundance in the bulking viromes, implying that phage
      mediated lysis might contribute to the loss of autotrophic nitrifiers under
      bulking conditions.

PMID- 28755264
TI  - Patient satisfaction and safety profile with sedation during gastrointestinal
      endoscopy.

PMID- 28755266
TI  - Latiglutenase Improves Symptoms in Seropositive Celiac Disease Patients While on
      a Gluten-Free Diet.
AB  - BACKGROUND AND AIMS: Celiac disease (CD) is a widespread condition triggered by
      dietary gluten and treated with a lifelong gluten-free diet (GFD); however,
      inadvertent exposure to gluten can result in episodic symptoms. A previous trial
      of latiglutenase (clinicaltrials.gov; NCT01917630), an orally administered
      mixture of two recombinant gluten-specific proteases, was undertaken in
      symptomatic subjects with persistent injury. The primary endpoint for histologic
      improvement was not met, presumably due to a trial effect. In this post hoc
      analysis, we investigated the efficacy of latiglutenase for reducing symptoms in
      subgroups of the study participants based on their seropositivity. METHODS: The
      study involved symptomatic CD patients following a GFD for at least one year
      prior to randomization. Patients were treated for 12 weeks with latiglutenase or
      placebo. Of 398 completed patients, 173 (43%) were seropositive at baseline.
      Symptoms were recorded daily, and weekly symptom scores were compiled. p values
      were calculated by analysis of covariance. RESULTS: A statistically significant,
      dose-dependent reduction was detected in the severity and frequency of symptoms
      in seropositive but not seronegative patients. The severity of abdominal pain and
      bloating was reduced by 58 and 44%, respectively, in the cohort receiving the
      highest latiglutenase dose (900 mg, n = 14) relative to placebo (n = 54). Symptom
      improvement increased from week 6 to week 12. There was also a trend toward
      greater symptom improvement with greater baseline symptom severity. CONCLUSIONS:
      Seropositive CD patients show symptomatic improvement from latiglutenase taken
      with meals and would benefit from the availability of this treatment.

PMID- 28755265
TI  - An in silico strategy for identification of novel drug targets against Plasmodium
      falciparum.
AB  - The apicomplexan parasite Plasmodium falciparum is responsible for global malaria
      burden. With the reported resistance to artemisinin chemotherapy, there is an
      urgent need to maintain early phase drug discovery and identify novel drug
      targets for successful eradication of the pathogen from the host. In our previous
      work on comparative genomics study for identification of putative essential genes
      and therapeutic candidates in P. falciparum, we predicted 11 proteins as anti
      malarial drug targets from PlasmoDB database. In this paper, we made an attempt
      for identification of novel drug targets in P. falciparum genome using a sequence
      of computational methods from Malaria Parasite Metabolic Pathway database. The
      study reported the identification of 71 proteins as potential drug targets for
      anti-malarial interventions. Furthermore, homology modeling and molecular dynamic
      simulation study of one of the potential drug targets, aminodeoxychorismate
      lyase, was carried to predict the 3D structure of the protein. Structure and
      ligand-based drug designing reported MMV019742 from Pathogen Box and TCAMS-141515
      from GSK-TCAMS library as potential hits. The reliability of the binding mode of
      the inhibitors is confirmed by GROMACS for a simulation time of 20 ns in water
      environment. This will be helpful for experimental validation of the small
      molecule inhibitor.

PMID- 28755267
TI  - Effect of mixed feeds containing different levels of olive cake on fattening
      performance, carcass, meat quality and fatty acids of lambs.
AB  - In this study, the effects of diet including different levels of olive cake were
      investigated on the fattening performance, blood parameters, certain slaughtering
      traits, and carcass quality of lambs. Thirty-six male lambs were used in the
      experiment. The lambs were randomly assigned to three groups with 12 lambs each.
      Groups included control, 12.5 and 25% olive cake (OC). The mixed feeds were
      offered ad libitum. All lambs were also allowed to consume alfalfa hay (83.8 g
      DM/animal/day). The experiment lasted for a period of 56 days. The effect of
      different levels of olive cake was not found different in fattening performance
      values of lambs in 0-56 days (P > 0.05). Carcass weight, pH, and yield were not
      different (P > 0.05). While the values of color parameters, cooking loss,
      tenderness, and ether extract level of longissimus dorsi muscle (MLD) was not
      found different (P > 0.05), it was determined that the levels of olive cake
      increased the water-holding capacity of meat (P < 0.05). Furthermore, although
      the levels of olive cake were shown to decrease total n-3 and total saturated
      fatty acids (Sigma SFA), they also increased total n-6, n-6/n-3 ratio, total
      monounsaturated fatty acids (Sigma MUFA), and total polyunsaturated fatty acids
      (Sigma PUFA) were not different (P > 0.05).

PMID- 28755268
TI  - Photoreceptor cells produce inflammatory products that contribute to retinal
      vascular permeability in a mouse model of diabetes.
AB  - AIMS/HYPOTHESIS: Recent studies suggest that photoreceptor cells produce
      mediators or products that contribute to retinal capillary damage in diabetes.
      The purpose of this study was to determine if photoreceptor cells release soluble
      factors that contribute to retinal vascular permeability in diabetes. METHODS: To
      assess retinal vascular leakage, a streptozotocin-induced mouse model of
      diabetes, with hyperglycaemia for 8 months, and age-matched control mice, were
      injected with FITC-BSA. Fluorescence microscopy was used to detect leakage of
      FITC-BSA from the retinal vasculature into the neural retina. Ex vivo and in
      vitro experiments were performed to determine if photoreceptor cells released
      products that directly increased retinal endothelial cell permeability or cell
      death. Effects of products released by photoreceptors on tight junction and cell
      adhesion proteins were assessed by quantitative reverse transcription PCR (qRT
      PCR). Inflammatory products released by photoreceptors into media were measured
      using protein arrays. RESULTS: Eight months duration of diabetes increased
      retinal vascular permeability in wild-type mice, but this defect was inhibited in
      opsin-deficient diabetic mice in which photoreceptor cells had degenerated
      earlier. Photoreceptor cells from diabetic wild-type mice released inflammatory
      products (e.g. IL-1alpha, IL-1beta, IL-6, IL-12, chemokine C-X-C motif ligand 1
      [CXCL1], monocyte chemoattractant protein 1 [MCP-1], CXCL12a, I-309, chemokine
      ligand 25 [CCL25] and TNF-alpha), which directly contributed to increased retinal
      endothelial cell permeability, at least in part via changes in claudin (tight
      junction) mRNA. Products released from photoreceptor cells from diabetic mice or
      under diabetes-like conditions did not directly kill retinal endothelial cells in
      vitro. CONCLUSIONS/INTERPRETATION: Photoreceptor cells can produce inflammatory
      products that contribute to retinal vascular permeability in mouse models of
      diabetes.

PMID- 28755269
TI  - Automatic Torso Detection in Images of Preterm Infants.
AB  - Imaging systems have applications in patient respiratory monitoring but with
      limited application in neonatal intensive care units (NICU). In this paper we
      propose an algorithm to automatically detect the torso in an image of a preterm
      infant during non-invasive respiratory monitoring. The algorithm uses normalised
      cut to segment each image into clusters, followed by two fuzzy inference systems
      to detect the nappy and torso. Our dataset comprised overhead images of 16
      preterm infants in a NICU, with uncontrolled illumination, and encompassing
      variations in poses, presence of medical equipment and clutter in the background.
      The algorithm successfully identified the torso region for 15 of the 16 images,
      with a high agreement between the detected torso and the torso identified by
      clinical experts.

PMID- 28755270
TI  - Embodied Conversational Agents for the Detection and Prevention of Suicidal
      Behaviour: Current Applications and Open Challenges.
AB  - Embodied conversational agents (ECAs) are advanced computational interactive
      interfaces designed with the aim to engage users in the continuous and long-term
      use of a background application. The advantages and benefits of these agents have
      been exploited in several e-health systems. One of the medical domains where ECAs
      are recently applied is to support the detection of symptoms, prevention and
      treatment of mental health disorders. As ECAs based applications are increasingly
      used in clinical psychology, and due that one fatal consequence of mental health
      problems is the commitment of suicide, it is necessary to analyse how current
      ECAs in this clinical domain support the early detection and prevention of risk
      situations associated with suicidality. The present work provides and overview of
      the main features implemented in the ECAs to detect and prevent suicidal
      behaviours through two scenarios: ECAs acting as virtual counsellors to offer
      immediate help to individuals in risk; and ECAs acting as virtual patients for
      learning/training in the identification of suicide behaviours. A literature
      review was performed to identify relevant studies in this domain during the last
      decade, describing the main characteristics of the implemented ECAs and how they
      have been evaluated. A total of six studies were included in the review
      fulfilling the defined search criteria. Most of the experimental studies indicate
      promising results, though these types of ECAs are not yet commonly used in
      routine practice. The identification of some open challenges for the further
      development of ECAs within this domain is also discussed.

PMID- 28755271
TI  - Multiclassifier Systems for Predicting Neurological Outcome of Patients with
      Severe Trauma and Polytrauma in Intensive Care Units.
AB  - This paper presents an ensemble based classification proposal for predicting
      neurological outcome of severely traumatized patients. The study comprises both
      the whole group of patients and a subgroup containing those patients suffering
      traumatic brain injury (TBI). Data was gathered from patients hospitalized in the
      Intensive Care Unit (ICU) of the University Hospital in Salamanca. Predictive
      models were induced from both epidemiologic and clinical variables taken at the
      emergency room and along the stay in the ICU. The large number of variables leads
      to a low accuracy in the classifiers even when feature selection methods are
      used. In addition, the presence of a much larger number of instances of one of
      the classes in the subgroup of TBI patients produces a significantly lesser
      precision for the minority class. Usual ways of dealing with the last problem is
      to use undersampling and oversampling strategies, which can lead to the loss of
      valuable data and overfitting problems respectively. Our proposal for dealing
      with these problems is based in the use of ensemble multiclassifiers as well as
      in the use of an ensemble playing the role of base classifier in
      multiclassifiers. The proposed strategy gave the best values of the selected
      quality measures (accuracy, precision, sensitivity, specificity, F-measure and
      area under the Receiver Operator Characteristic curve) as well as the closest
      values of precision for the two classes under study in the case of the
      classification from imbalanced data.

PMID- 28755272
TI  - Polymorphism and methylation of the MC4R gene in obese and non-obese dogs.
AB  - The dog is considered to be a useful biomedical model for human diseases and
      disorders, including obesity. One of the numerous genes associated with human
      polygenic obesity is MC4R, encoding the melanocortin 4 receptor. The aim of our
      study was to analyze polymorphisms and methylation of the canine MC4R in relation
      to adiposity. Altogether 270 dogs representing four breeds predisposed to
      obesity: Labrador Retriever (n = 187), Golden Retriever (n = 38), Beagle (n = 28)
      and Cocker Spaniel (n = 17), were studied. The dogs were classified into three
      groups: lean, overweight and obese, according to the 5-point Body Condition Score
      (BCS) scale. In the cohort of Labradors a complete phenotypic data (age, sex,
      neutering status, body weight and BCS) were collected for 127 dogs. The entire
      coding sequence as well as 5' and 3'-flanking regions of the studied gene were
      sequenced and six polymorphic sites were reported. Genotype frequencies differed
      considerably between breeds and Labrador Retrievers appeared to be the less
      polymorphic. Moreover, distribution of some polymorphic variants differed
      significantly (P < 0.05) between small cohorts with diverse BCS in Golden
      Retrievers (c.777T>C, c.868C>T and c.*33C>G) and Beagles (c.-435T>C and
      c.637G>T). On the contrary, in Labradors no association between the studied
      polymorphisms and BCS or body weight was observed. Methylation analysis, using
      bisulfite DNA conversion followed by Sanger sequencing, was carried out for 12
      dogs with BCS = 3 and 12 dogs with BCS = 5. Two intragenic CpG islands,
      containing 19 cytosines, were analyzed and the methylation profile did not differ
      significantly between lean and obese animals. We conclude that an association of
      the MC4R gene polymorphism with dog obesity or body weight is unlikely, in spite
      of the fact that some associations were found in small cohorts of Beagles and
      Golden Retrievers. Also methylation level of this gene is not related with dog
      adiposity.

PMID- 28755273
TI  - Cognitive Impairment and Brain and Peripheral Alterations in a Murine Model of
      Intraventricular Hemorrhage in the Preterm Newborn.
AB  - Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) remains a
      serious complication in the preterm newborn. The significant increase of survival
      rates in extremelye preterm newborns has also contributed to increase the
      absolute number of patients developing GMH-IVH. However, there are relatively few
      available animal models to understand the underlying mechanisms and peripheral
      markers or prognostic tools. In order to further characterize central
      complications and evolution of GMH-IVH, we injected collagenase
      intraventricularly to P7 CD1 mice and assessed them in the short (P14) and the
      long term (P70). Early complications at P14 included ventricle enlargement,
      increased bleeding, and inflammation. These alterations were maintained at P70,
      when increased tau phosphorylation and decreased neurogenesis were also observed,
      resulting in impaired learning and memory in these early adult mice. We
      additionally analyzed peripheral blood biomarkers in both our mouse model and
      preterm newborns with GMH-IVH. While MMP9 levels were not significantly altered
      in mice or newborns, reduced gelsolin levels and increased ubiquitin carboxy
      terminal hydrolase L1 and tau levels were detected in GMH-IVH patients at birth.
      A similar profile was observed in our mouse model after hemorrhage.
      Interestingly, early changes in gelsolin and carboxy-terminal hydrolase L1 levels
      significantly correlated with the hemorrhage grade in newborns. Altogether, our
      data support the utility of this animal model to reproduce the central
      complications and peripheral changes observed in the clinic, and support the
      consideration of gelsolin, carboxy-terminal hydrolase L1, and tau as feasible
      biomarkers to predict the development of GMH-IVH.

PMID- 28755274
TI  - Regression of Left Ventricular Mass After Bariatric Surgery.
AB  - Notwithstanding the presence of hypertension, obstructive sleep apnea, or both,
      obesity is associated with increased left ventricular (LV) mass. The effects of
      bariatric surgery on LV mass have been sparsely investigated by M-mode and two
      dimensional (2D) echocardiography. Overall, Roux-en-Y gastric bypass, adjustable
      gastric banding, and sleeve gastrectomy reduce LV mass. However, the reduction in
      LV mass is extremely variable. Besides duration and severity of obesity, presence
      of hypertension, obstructive sleep apnea or both, and type of surgical
      procedures, the inaccuracy of M-mode and 2D echocardiography for assessment of LV
      mass contributes to the variable effects of bariatric surgery on LV mass. Three
      dimensional (3D) echocardiography may obviate the limitations of M-mode 2D
      echocardiography for assessment of LV mass and allow an accurate appraisal of the
      effects of bariatric surgery on LV mass.

PMID- 28755275
TI  - Neighborhoods, Schools, and Academic Achievement: A Formal Mediation Analysis of
      Contextual Effects on Reading and Mathematics Abilities.
AB  - Although evidence indicates that neighborhoods affect educational outcomes,
      relatively little research has explored the mechanisms thought to mediate these
      effects. This study investigates whether school poverty mediates the effect of
      neighborhood context on academic achievement. Specifically, it uses longitudinal
      data from the Panel Study of Income Dynamics, counterfactual methods, and a value
      added modeling strategy to estimate the total, natural direct, and natural
      indirect effects of exposure to an advantaged rather than disadvantaged
      neighborhood on reading and mathematics abilities during childhood and
      adolescence. Contrary to expectations, results indicate that school poverty is
      not a significant mediator of neighborhood effects during either developmental
      period. Although moving from a disadvantaged neighborhood to an advantaged
      neighborhood is estimated to substantially reduce subsequent exposure to school
      poverty and improve academic achievement, school poverty does not play an
      important mediating role because even the large differences in school composition
      linked to differences in neighborhood context appear to have no appreciable
      effect on achievement. An extensive battery of sensitivity analyses indicates
      that these results are highly robust to unobserved confounding, alternative model
      specifications, alternative measures of school context, and measurement error,
      which suggests that neighborhood effects on academic achievement are largely due
      to mediating factors unrelated to school poverty.

PMID- 28755276
TI  - Decomposing Current Mortality Differences Into Initial Differences and
      Differences in Trends: The Contour Decomposition Method.
AB  - This study proposes a new decomposition method that permits a difference in an
      aggregate measure at a final time point to be split into additive components
      corresponding to the initial differences in the event rates of the measure and
      differences in trends in these underlying event rates. For instance, when
      studying divergence in life expectancy, this method allows researchers to more
      easily contrast age-specific mortality trends between populations by controlling
      for initial age-specific mortality differences. Two approaches are assessed: (1)
      an additive change method that uses logic similar to cause-of-death
      decomposition, and (2) a contour decomposition method that extends the stepwise
      replacement algorithm along an age-period demographic contour. The two approaches
      produce similar results, but the contour method is more widely applicable. We
      provide a full description of the contour replacement method and examples of its
      application to life expectancy and lifetime disparity differences between the
      United States and England and Wales in the period 1980-2010.

PMID- 28755277
TI  - Chronic Remote Ischemic Conditioning Is Cerebroprotective and Induces Vascular
      Remodeling in a VCID Model.
AB  - Vascular contributions to cognitive impairment and dementia (VCID) make up 50% of
      the cases of dementia. The purpose of this study was to determine the effect of
      chronic remote ischemic conditioning (C-RIC) on improving long-term (6 months)
      outcomes and cerebral blood flow (CBF) and collateral formation in a mouse model
      of VCID. Adult C57BL/6J male mice (10 weeks) were randomly assigned to four
      different groups: (1) sham-bilateral carotid artery stenosis (BCAS), (2) BCAS +
      sham RIC, (3) BCAS+C-RIC for 1 month (1MO), and (4) BCAS+C-RIC-4 months (4MO).
      CBF, cognitive impairment, and functional outcomes were performed up for 6 months
      after BCAS surgery. The expression of CD31, alpha-SMA, and myelin basic protein
      (MBP) was assessed by immunohistochemistry (IHC). Additional set of mice were
      randomized to sham, BCAS, and BCAS+C-RIC. The cerebrovascular angioarchitecture
      was studied with micro-CT. RIC therapy for either 1 or 4 months significantly
      improved CBF, new collateral formation, functional and cognitive outcomes, and
      prevented white matter damage. There was no difference between C-RIC for 1 or 4
      months; IHC studies at 6 months showed an increase in brain CD31 and alpha-SMA
      expression indicating increased angiogenesis and MBP indicating preservation of
      white matter in animals receiving RIC. One month of daily RIC is as effective as
      4 months of daily RIC in improving CBF, angiogenesis, and long-term functional
      outcomes (6 months) in a VCID model. This suggests that 1 month of RIC is
      sufficient to reduce cognitive impairment and induce beneficial cerebrovascular
      remodeling.

PMID- 28755279
TI  - In Vitro Methods to Study the Modulation of Migration and Invasion by Sphingosine
      1-Phosphate.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive lipid that modulates migratory
      behavior of cells during embryonic development. In addition, S1P might promote
      tumor progression by enhancing migratory ability and invasiveness of tumor cells.
      Migration is a complex process that implies cytoskeletal reorganization and
      formation of structures that enable cell movement. Besides having similar
      requirements than migration, invasion also involves proteolytic degradation of
      extracellular matrix (ECM). Matrix metalloproteases (MMPs) have been identified
      to break down components of the ECM, allowing cancer cells to spread out of the
      primary tumor. In this chapter, we will describe different techniques to study
      migration and invasion induced by S1P. To this end, we include detailed protocols
      of end-point assays to study migration/invasion, and zymography assay to analyze
      MMP-2 and MMP-9 activity that were standardized in our laboratory in human
      melanoma cell lines.

PMID- 28755278
TI  - Endothelial BMP4 Regulates Leukocyte Diapedesis and Promotes Inflammation.
AB  - Leukocyte recruitment is a fundamental event in the response of the innate immune
      system to injury. This process is promoted in part by the opening of endothelial
      cell adherens junctions that allows leukocyte extravasation through gaps between
      adjacent endothelial cells. VE-cadherin is a key component of endothelial cell
      adherens junctions and a negative regulator of leukocyte emigration. Accumulating
      evidence implicates bone morphogenetic protein (BMP) 4 as a critical regulator in
      vascular biology, but its role in leukocyte extravasation in vitro and in vivo
      has not been investigated so far. To assess the impact of BMP4 on leukocyte
      emigration in vivo, we used the thioglycollate-induced peritonitis model. C57BL/6
      mice were intraperitoneally (i.p.) injected with recombinant BMP4 in addition to
      thioglycollate. Compared to solvent-treated controls, we observed higher
      accumulation of leukocytes in the peritoneal lavage of BMP4-treated mice
      indicating that BMP4 promotes leukocyte diapedesis into the inflamed peritoneal
      cavity. Endothelial cell-specific deletion of BMP4 in mice markedly diminished
      leukocyte diapedesis following thioglycollate administration suggesting that
      endothelial BMP4 is required for leukocyte recruitment. Consistent with these in
      vivo results, transwell migration assays with human umbilical vein endothelial
      cells (HUVECs) in vitro revealed that recombinant BMP4 enhanced leukocyte
      transmigration through the endothelial monolayer. Conversely, silencing of
      endothelial BMP4 by siRNA dampened leukocyte diapedesis in vitro. Mechanistic
      studies showed that loss of BMP4 improved endothelial junction stability by
      upregulation of VE-cadherin expression in vitro and in vivo. Vice versa,
      treatment of HUVECs with recombinant BMP4 decreased expression of VE-cadherin and
      impaired endothelial junction stability shown by Western blotting and
      immunocytochemistry. Finally, severe endothelial damage in HUVECs in response to
      serum of patients collected 24 h after survived cardiac arrest was accompanied by
      increase in leukocyte migration in transwell assays and activation of the BMP
      pathway most probably by upregulation of endothelial BMP4 RNA and protein
      expression. Collectively, the present study provides novel evidence that
      endothelial BMP4 controls leukocyte recruitment through a VE-cadherin-dependent
      mechanism and that BMP4-induced inflammation might be involved in the
      pathogenesis of endothelial cell damage following successful resuscitation after
      cardiac arrest.

PMID- 28755280
TI  - Magnetic resonance imaging patterns of mononeuropathic denervation in muscles
      with dual innervation.
AB  - Magnetic resonance imaging (MRI) of mononeuropathy in muscles with dual
      innervation depicts geographic denervation corresponding to the affected nerve.
      Knowledge of the normal distribution of a muscle's neural supply is clinically
      relevant as partial muscle denervation represents a potential imaging pitfall
      that can be confused with other pathology, such as muscle strain. This article
      reviews the normal innervation pattern of extremity muscles with dual supply,
      providing illustrative examples of mononeuropathy affecting such muscles.

PMID- 28755281
TI  - Radiation-induced focal cortical necrosis of the femur presenting as a lytic
      lesion.
AB  - Management of soft tissue sarcomas is often complicated, requiring radiation
      before and in some cases after limb-sparing surgery. Radiation necrosis is a
      severe complication after radiation treatment and is typically dose related and
      involves medullary bone. We report on two cases of hitherto unreported focal
      circumscribed intra-cortical lytic lesions within the radiation portal, which
      appeared 19 months and 31 months, respectively, after the conclusion of radiation
      treatment. Both patients had a history of soft tissue sarcoma treated with
      radiation (66 Gy) and surgical resection. Biopsy of these lesions showed necrotic
      bone attributed to radiation.

PMID- 28755282
TI  - Scaphoid fracture: Bone marrow edema detected with dual-energy CT virtual non
      calcium images and confirmed with MRI.
AB  - We aimed to determine whether bone marrow edema (BME) in acute traumatic scaphoid
      fracture could be demonstrated with dual-energy CT (DECT) using MRI as the gold
      standard. In recent years, virtual non-calcium (VNCa) images have been used to
      demonstrate BME in trauma cases, for example, in vertebral compression fractures,
      hip trauma to detect occult fractures and knee fractures. We present three cases
      of acute scaphoid trauma. Two patients had subtle or invisible fractures on x-ray
      and conventional CT images, while DECT VNCa images clearly visualized the BME,
      which was confirmed by MRI. One patient had negative findings on both VNCa and
      MRI images. The DECT VNCa algorithm is a promising technique to demonstrate BME
      in scaphoid fractures, with potential for increasing the diagnostic value of CT
      in this type of injury.

PMID- 28755283
TI  - Adsorptive detoxification of fermentation inhibitors in acid pretreated liquor
      using functionalized polymer designed by molecular simulation.
AB  - Acid pretreatment is the most common method employed in the lignocellulosic
      biorefinery leading to the separation of pentose and hexose sugar. The liquor
      obtained after pretreatment (acid pretreatment liquor or APL) needs to be
      detoxified prior to fermentation. The aim of this study was to design functional
      groups on a polymer matrix which are selective in their interaction to inhibitors
      with little or no specificity to sugars. Molecular modeling was used as a tool to
      design a suitable adsorbent for selective adsorption of inhibitors from a complex
      mixture of APL. Phenyl glycine-p-sulfonic acid loaded on chloromethylated
      polystyrene polymer was designed as an adsorbent for selective interaction with
      inhibitors. Experimental verification of the selectivity was successfully
      achieved. The current study provides insights on the adsorptive separation
      processes at the molecular level by design of specific adsorbent which can be
      tailor made for the better selectivity of the desired component.

PMID- 28755284
TI  - Morphological anomalies in Ixodes ricinus and Ixodes inopinatus collected from
      tick-borne encephalitis natural foci in Central Europe.
AB  - In 2015, 0.02% nymphs displayed anomalies (ectromely) out of the 6744 collected
      ticks as part of a tick-borne encephalitis program in Germany. In 2016, questing
      Ixodes ricinus (n = 14,527) and Ixodes inopinatus (n = 75) ticks were collected
      by flagging as part of a tick-borne encephalitis program in Germany, Slovakia and
      Denmark. A total of 278 (1.9%) out of 14,602 nymph and adult ticks showed
      morphological anomalies. The anomalies were divided into general anomalies (body
      asymmetry) and local anomalies (anomalies of appendages, malformation of
      capitulum, exoskeleton anomalies and anal groove deformation) with nymphs being
      the most affected life stage. Most important, leg atrophy was the most common
      anomaly (209 nymphs, 11 females and three males) followed by asymmetry (10
      nymphs, five females and a male) and ectromely (nine nymphs). Two females and one
      male displayed multiple anomalies on legs, palps and exoskeleton. Anal groove
      deformation was observed in three females and three nymphs. In 2016, the
      frequency of anomalies in I. inopinatus was found five times higher (9.3%) than
      in I. ricinus (1.9%). This is the first report of anomaly (ectromely, leg
      atrophy, idiosoma deformation) in flagged I. inopinatus and the first report of
      schizomely in I. ricinus.

PMID- 28755285
TI  - Two-year follow-up of 4 months metformin treatment vs. placebo in ST-elevation
      myocardial infarction: data from the GIPS-III RCT.
AB  - OBJECTIVES: Preclinical and clinical studies suggested cardioprotective effects
      of metformin treatment. In the GIPS-III trial, 4 months of metformin treatment
      did not improve left ventricular ejection fraction in patients presenting with ST
      elevation myocardial infarction (STEMI). Here, we report the 2-year follow-up
      results. METHODS: Between January 2011 and May 2013, 379 STEMI patients without
      diabetes undergoing primary percutaneous coronary intervention were randomized to
      a 4-month treatment with metformin (500 mg twice daily) (N = 191) or placebo (N =
      188) in the University Medical Center Groningen. Two-year follow-up data was
      collected to determine its effect on predefined secondary endpoints: the
      incidence of major adverse cardiac events (MACE), its individual components, all
      cause mortality, and new-onset diabetes. RESULTS: For all 379 patients all-cause
      mortality data were available. For seven patients (2%) follow-up data on MACE was
      limited, ranging from 129 to 577 days. All others completed the 2-year follow-up
      visit. Incidence of MACE was 11 (5.8%) in metformin and 6 (3.2%) in placebo
      treated patients [hazard ratio (HR) 1.84, confidence interval (CI) 0.68-4.97, P =
      0.22]. Three patients died in the metformin group and one in the placebo
      treatment group. Individual components of MACE were also comparable between both
      groups. New-onset diabetes mellitus was 34 (17.8%) in metformin and 32 (17.0%) in
      placebo treated patients (odds ratio 1.15, CI 0.66-1.98, P = 0.84). After
      multivariable adjustment the incidence of MACE was comparable between the
      treatment groups (HR 1.02, CI 0.10-10.78, P = 0.99). CONCLUSIONS: Four months
      metformin treatment initiated at the time of hospitalization in STEMI patients
      without diabetes did not exert beneficial long-term effects. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01217307.

PMID- 28755286
TI  - Assessment of arsenic trioxide toxicity on cock muscular tissue: alterations of
      oxidative damage parameters, inflammatory cytokines and heat shock proteins.
AB  - To evaluate the toxicity of arsenic trioxide (As2O3) in the muscular tissues
      (wing, thigh and pectoral) of birds, 72 one-day-old Hy-line cocks were selected
      and randomly divided into four groups. They were fed either a commercial diet or
      an arsenic-supplemented diet containing 7.5, 15 or 30 mg/kg As2O3. The experiment
      lasted for 90 days and the samples of muscular tissues were collected at 30, 60
      and 90 days. The results showed that As2O3 exposure significantly lowered the
      activities of antioxidant enzymes (catalase (CAT), glutathione peroxidase (GSH
      Px)) and inhibition ability of hydroxyl radicals (OH) and increased the
      malondialdehyde (MDA) contents. Furthermore, the mRNA levels of inflammatory
      cytokines (tumor necrosis factor-alpha (TNF-alpha), nuclear factor-kappa B (NF
      kappaB), cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), prostaglandin E
      synthase (PTGEs)) and heat shock proteins (HSPs) in muscular tissue were
      significantly upregulated in the As2O3 exposure groups. The results indicated
      that As2O3 exposure resulted in oxidative damage, induced the inflammatory
      response, and influenced the mRNA levels of HSPs in muscular tissue of cocks.
      Additionally, the results suggested that HSPs possibly resisted due to the As2O3
      exposure-induced oxidative stress and inflammatory response, which provided a
      favorable environment and played protective roles in the muscular tissues of
      cocks. The information presented in this study is helpful to understand the
      mechanism of As2O3 toxicity in bird muscular tissues.

PMID- 28755287
TI  - Evaluation of the impact of bioaccumulation of PAH from the marine environment on
      DNA integrity and oxidative stress in marine rock oyster (Saccostrea cucullata)
      along the Arabian sea coast.
AB  - Marine pollution due to oil spills is of great concern globally for their impact
      on the health of marine ecosystems. We assessed the genotoxic effects and
      oxidative stress due to genotoxic pollutants accumulated from the ambient marine
      environment in the tissues of marine rock oyster, Saccostrea cucullata along the
      Arabian Sea coast around Goa, India. The extent of DNA damage in S. cucullata was
      determined by comet assay as variation of comet parameter: mean % tail DNA along
      the coast with respect to that at the reference site (Tiracol, Goa, India). In
      addition, the oxidative stress responses of rock oysters exposed to marine
      pollutants such as polycyclic aromatic hydrocarbons (PAHs) were assessed as a
      function of variation in antioxidant enzyme activities such as glutathione-s
      transferase (GST), catalase (CAT) and superoxide dismutase (SOD) along the coast.
      Spearman correlation analysis showed significant correlation between different
      components of PAHs (viz., 2-3-PAH, 4-6-PAH and oxy-PAH) in the tissues of the
      rock oysters and the antioxidant enzyme activities. The antioxidant enzyme
      activities in S. cucullata increased with increasing concentrations of PAHs in
      tissues in the following order of sampling sites: Tiracol < Arambol < Betul <
      Velsao. Among the PAHs, oxy-PAH was found to be most predominant in causing DNA
      damage in S. cucullata. These results provide an insight into environmental
      genotoxicity and oxidative stress induced by PAHs along the Arabian Sea coast,
      India.

PMID- 28755288
TI  - Neuroprotective Effect of Chitosan Oligosaccharide on Hypoxic-Ischemic Brain
      Damage in Neonatal Rats.
AB  - Neonatal hypoxic-ischemic brain damage (HIBD) is one of the leading causes of
      neonatal mortality and permanent neurological disability worldwide and the
      effective treatment strategies are not yet available. It has been demonstrated
      that Chitosan oligosaccharide (COS) exerts protective effect in vitro ischemic
      brain injury. However, no information is available on possible effects of COS on
      neonatal HIBD. To investigate the hypothesis of the potential neuroprotective
      effect of COS on the brain injury due to HIBD, 7-day-old Sprague-Dawley rats were
      treated with left carotid artery ligation followed by exposure to 8% oxygen
      (balanced with nitrogen) for 2.5 h at 37  degrees C. After COS treatment, the
      cerebral damage was measured by behavior tasks, 2,3,5-triphenyltetrazolium
      chloride(TTC), Hematoxyline-Eosin(HE), Nissl and Fluoro-Jade B(FJB)staining. In
      addition, the oxidative stress were assayed with ipsilateral hemisphere
      homogenates. Immunofluorescence staining were used to examine the activation of
      the astrocyte and microglia. Expression of inflammatory-related proteins were
      analyzed by western-blot analysis. In this study we found that administration of
      COS ameliorated early neurological reflex behavior, significantly reduce brain
      infarct volume and attenuated neuronal cell injury and degeneration. Furthermore,
      COS markedly decreased the level of MDA, lactic acid and increased SOD, GSH-Px
      and T-AOC. COS attenuated hypoxic-ischemic induced up-regulation of expressions
      of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha),
      meanwhile it dramatically increased the interleukin-10 (IL-10). These results
      suggest that COS exerts neuroprotection on hypoxic-ischemic brain damage in
      neonatal rats, it implies COS might be a potential therapeutic for the treatment
      of HIBD.

PMID- 28755289
TI  - Downregulation of USP4 Promotes Activation of Microglia and Subsequent Neuronal
      Inflammation in Rat Spinal Cord After Injury.
AB  - NF-kappaB is involved in the activation of microglia, which induces secondary
      spinal cord injury (SCI). This process involves the activation of NF-kappaB
      signaling pathway by TRAF6 through its polyubiquitination function. We know that
      deubiquitination of TRAF6 mediated by deubiquitinating enzyme (DUB) significantly
      inhibits activation of NF-kappaB pathway. The ubiquitin-specific protease 4
      (USP4) belongs to the deubiquitinase family. Therefore, we hypothesize that USP4
      is involved in the microglial activation and subsequent neuronal inflammation
      after SCI. In this study, we examined the expression and the role of USP4 after
      SCI. Western blot analysis showed that the expression of USP4 was downregulated
      and the expression of p-p65 was upregulated in the spinal cord after SCI.
      Immunohistochemical and immunofluorescence staining showed that USP4 was
      expressed in microglia but its expression decreased after SCI. In vitro LPS
      induced activation of microglia showed decreased expression of USP4 and increased
      expression of p-p65 and TRAF6. USP4 silencing in LPS-induced activation of
      microglia promoted the expression of p-p65 and TRAF6 and the secretion of TNF
      alpha and IL-1beta. In conclusion, our study provides the first evidence that in
      microglial cells expression of USP4 decreases after SCI in rats. The
      downregulation of USP4 expression may promote microglial activation and
      subsequent neuronal inflammation through NF-kappaB by attenuating the
      deubiquitination of TRAF6. This mechanism is of great significance in the
      pathophysiology of secondary SCI.

PMID- 28755290
TI  - Barriers to systemic application of virus-based vectors in gene therapy: lessons
      from adenovirus type 5.
AB  - Currently, virus-based vectors, namely derivatives of the adenovirus, are
      frequently used in a wide variety of ex vivo or local gene therapeutic
      applications. However, the efficacy of virus-based vectors in systemic
      applications is presently still extremely limited. Complex interactions of the
      various vector types with the patient's organism hinder successful vector
      deployment. Exemplary, here we summarize barriers to systemic application of
      Adenovirus-based vectors leading either to acute toxic effects or rapid vector
      neutralization and discuss strategies to overcome these barriers aiming to
      develop more efficient vector types.

PMID- 28755291
TI  - Expression of pathogenesis-related genes in cotton roots in response to
      Verticillium dahliae PAMP molecules.
AB  - Verticillium wilt disease becomes a major threat to many economically important
      crops. It is unclear whether and how plant immunity takes place during cotton
      Verticillium interaction due to the lack of marker genes. Taking advantage of
      cotton (Gossypium hirsutum) genome, we discovered pathogenesis-related (PR) gene
      families, which have been widely used as markers of immune responses in plants.
      To profile the expression of G. hirsutum PR genes in the process of plant
      immunity, we treated cotton roots with two immunogenic peptides, flg22 and nlp20
      known as pathogen-associated molecular patterns, as well as three Verticillium
      dahliae-derived peptides, nlp20Vd2, nlp23Vd3, and nlp23Vd4 which are highly
      identical to nlp20. Quantitative real-time PCR results revealed that 14 G.
      hirsutum PR gene (GhPR) families were induced or suppressed independently in
      response to flg22, nlp20, nlp20Vd2, nlp23Vd3, and nlp23Vd4. Most GhPR genes are
      expressed highest at 3 h post incubation of immunogenic peptides. Compared to
      flg22 and nlp20, nlp20Vd2 is more effective to trigger up-regulated expression of
      GhPR genes. Notably, both nlp23Vd3 and nlp23Vd4 are able to induce GhPR gene up
      regulation, although they do not induce necrosis on cotton leaves. Thus, our
      results provide marker genes and new immunogenic peptides for further
      investigation of cotton-V. dahliae interaction.

PMID- 28755292
TI  - Volatiles produced by bacteria alleviate antagonistic effects of one associated
      fungus on Dendroctonus valens larvae.

PMID- 28755293
TI  - Genome re-sequencing analysis uncovers pathogenecity-related genes undergoing
      positive selection in Magnaporthe oryzae.
AB  - Rice blast caused by Magnaporthe oryzae (M. oryzae) is one of the most
      destructive diseases, which causes significant rice yield losses and affects
      global food security. To better understand genetic variations among different
      isolates of M. oryzae in nature, we re-sequenced the genomes of two field
      isolates, CH43 and Zhong-10-8-14, which showed distinct pathogenecity on most of
      the rice cultivars. Genome-wide genetic variation analysis reveals that ZHONG-10
      8-14 exhibits higher sequence variations than CH43. Structural variations (SVs)
      detection shows that the sequence variations primarily occur in exons and
      intergenic regions. Bioinformatics analysis for gene variations reveals that many
      pathogenecity-related pathways are enriched. In addition, 193 candidate effectors
      with various DNA polymorphisms were identified, including two known effectors AVR
      Pik and AVR-Pita1. Comparative polymorphism analysis of thirteen randomly
      selected effectors suggests that the genetic variations of effectors are under
      positive selection. The expression pattern analysis of several pathogenecity
      related variant genes indicates that these genes are differentially regulated in
      two isolates, with much higher expression levels in Zhong-10-8-14 than CH43. Our
      data demonstrate that the genetic variations of effectors and pathogenecity
      related genes are under positive selection, resulting in the distinct
      pathogenicities of CH43 and Zhong-10-8-14 on rice.

PMID- 28755294
TI  - VdPKS1 is required for melanin formation and virulence in a cotton wilt pathogen
      Verticillium dahliae.
AB  - Verticillium dahliae is a soil-borne phytopathogenic fungus that causes vascular
      wilt disease in a broad range of hosts. This pathogen survives for many years in
      soil in the form of melanized microsclerotia. To investigate the melanin
      synthesis in V. dahliae, we identified a polyketide synthase gene in V. dahliae,
      namely VdPKS1. PKS1 is known to involve in the dihydroxynaphthalene melanin
      synthesis pathway in many fungi. We found that VdPKS1 was required for melanin
      formation but not for microsclerotial production in V. dahliae. The VdPKS1 gene
      disruption mutant (vdpks1) formed melanin-deficient albino microsclerotia, which
      did not affect the fungal colonization in host tissues but significantly reduced
      the disease severity. Gene transcription analysis in the wild-type and the vdpks1
      strains suggested that VdPKS1 gene-disruption influenced the expression of a
      series of genes involved in ethylene biosynthesis, microsclerotial formation and
      pathogenesis. Our results suggest that the VdPKS1-mediated melanin synthesis is
      important for virulence and developmental traits of V. dahliae.

PMID- 28755295
TI  - Centromere pairing precedes meiotic chromosome pairing in plants.
AB  - Meiosis is a specialized eukaryotic cell division, in which diploid cells undergo
      a single round of DNA replication and two rounds of nuclear division to produce
      haploid gametes. In most eukaryotes, the core events of meiotic prophase I are
      chromosomal pairing, synapsis and recombination. To ensure accurate chromosomal
      segregation, homologs have to identify and align along each other at the onset of
      meiosis. Although much progress has been made in elucidating meiotic processes,
      information on the mechanisms underlying chromosome pairing is limited in
      contrast to the meiotic recombination and synapsis events. Recent research in
      many organisms indicated that centromere interactions during early meiotic
      prophase facilitate homologous chromosome pairing, and functional centromere is a
      prerequisite for centromere pairing such as in maize. Here, we summarize the
      recent achievements of chromosome pairing research on plants and other organisms,
      and outline centromere interactions, nuclear chromosome orientation, and meiotic
      cohesin, as main determinants of chromosome pairing in early meiotic prophase.

PMID- 28755296
TI  - Improvement of oxytetracycline production mediated via cooperation of resistance
      genes in Streptomyces rimosus.
AB  - Increasing the self-resistance levels of Streptomyces is an effective strategy to
      improve the production of antibiotics. To increase the oxytetracycline (OTC)
      production in Streptomyces rimosus, we investigated the cooperative effect of
      three co-overexpressing OTC resistance genes: one gene encodes a ribosomal
      protection protein (otrA) and the other two express efflux proteins (otrB and
      otrC). Results indicated that combinational overexpression of otrA, otrB, and
      otrC (MKABC) exerted a synergetic effect. OTC production increased by 179% in the
      recombinant strain compared with that of the wild-type strain M4018. The
      resistance level to OTC was increased by approximately two-fold relative to the
      parental strain, thereby indicating that applying the cooperative effect of self
      resistance genes is useful to improve OTC production. Furthermore, the previously
      identified cluster-situated activator OtcR was overexpressed in MKABC in
      constructing the recombinant strain MKRABC; such strain can produce OTC of
      approximately 7.49 g L-1, which represents an increase of 19% in comparison with
      that of the OtcR-overexpressing strain alone. Our work showed that the
      cooperative overexpression of self-resistance genes is a promising strategy to
      enhance the antibiotics production in Streptomyces.

PMID- 28755297
TI  - Insecticide resistance status and detoxification enzymes of wheat aphids Sitobion
      avenae and Rhopalosiphum padi.

PMID- 28755298
TI  - Large manipulative experiments reveal complex effects of food supplementation on
      population dynamics of Brandt's voles.
AB  - Although food supplementation is well known to increase population density, there
      is still debate on the causative effects of food supplementation on reproduction,
      survival, and immigration. Large manipulative experiments, which exclude any
      confounding effects of dispersal and predation, are essential for clarifying the
      debate. In this study, we investigated the effects of food supplementation on
      Brandt's vole population dynamics and plant community in eight large enclosures
      (0.48 ha each) from 2010 to 2014. Food supplementation showed significant
      positive effects on population density due to increases in recruitment; however,
      it showed a complex effect on survival of voles: positive in non-breeding
      seasons, but negative in breeding seasons. In addition, food supplementation
      increased the quality of plants (as reflected by increased crude protein
      content), but decreased the quantity of less preferred plants in experimental
      enclosures. Thus, food seems to have direct positive effects on small rodents
      through improvement of food supply and indirect negative effects through food
      induced density-dependent effects, and may have long-term effects on rodents
      through altering plant community composition and abundance.

PMID- 28755299
TI  - Interkingdom signaling in plant-microbe interactions.
AB  - The widespread communications between prokaryotes and eukaryotes via signaling
      molecules are believed to affect gene expression in both partners. During the
      communication process, the contacted organisms produce and release small
      molecules that establish communication channels between two kingdoms-this
      procedure is known as interkingdom signaling. Interkingdom communications are
      widespread between pathogenic or beneficial bacteria and their host plants, with
      diversified outcomes depending on the specific chemical-triggered signaling
      pathways. Deciphering the signals or language of this interkingdom communication
      and uncovering the underlying mechanisms are major current challenges in this
      field. It is evident that diverse signaling molecules can be produced or derived
      from bacteria and plants, and researchers have sought to identify these signals
      and explore the mechanisms of the signaling pathways. The results of such studies
      will lead to the development of strategies to improve plant disease resistance
      through controlling interkingdom signals, rather than directly killing the
      pathogenic bacteria. Also, the identification of signals produced by beneficial
      bacteria will be useful for agricultural applications. In this review, we
      summarize the recent progress of cross-kingdom interactions between plant and
      bacteria, and how LuxR-family transcription factors in plant associated bacterial
      quorum sensing system are involved in the interkingdom signaling.

PMID- 28755300
TI  - In vivo gene expression profiling of the entomopathogenic fungus Beauveria
      bassiana elucidates its infection stratagems in Anopheles mosquito.
AB  - The use of entomopathogenic fungi to control mosquitoes is a promising tool for
      reducing vector-borne disease transmission. To better understand infection
      stratagems of insect pathogenic fungi, we analyzed the global gene expression
      profiling of Beauveria bassiana at 36, 60, 84 and 108 h after topical infection
      of Anopheles stephensi adult mosquitoes using RNA sequencing (RNA-Seq). A total
      of 5,354 differentially expressed genes (DEGs) are identified over the course of
      fungal infection. When the fungus grows on the mosquito cuticle, up-regulated
      DEGs include adhesion-related genes involved in cuticle attachment, Pth11-like
      GPCRs hypothesized to be involved in host recognition, and extracellular enzymes
      involved in the degradation and penetration of the mosquito cuticle. Once in the
      mosquito hemocoel, the fungus evades mosquito immune system probably through up
      regulating expression of beta-1,3-glucan degrading enzymes and chitin synthesis
      enzymes for remodeling of cell walls. Moreover, six previous unknown SSCP (small
      secreted cysteine-rich proteins) are significantly up-regulated, which may serve
      as "effectors" to suppress host defense responses. B. bassiana also induces large
      amounts of antioxidant genes to mitigate host-generated exogenous oxidative
      stress. At late stage of infection, B. bassiana activates a broad spectrum of
      genes including nutrient degrading enzymes, some transporters and metabolism
      pathway components, to exploit mosquito tissues and hemolymph as a nutrient
      source for hyphal growth. These findings establish an important framework of
      knowledge for further comprehensive elucidation of fungal pathogenesis and
      molecular mechanism of Beauveria-mosquito interactions.

PMID- 28755301
TI  - Complete genome sequence of a novel bacteriophage infecting Bradyrhizobium
      diazoefficiens USDA110.

PMID- 28755302
TI  - Per os infectivity factors: a complicated and evolutionarily conserved entry
      machinery of baculovirus.
AB  - Baculoviruses are a family of arthropod-specific large DNA viruses that infect
      insect species belonging to the orders Lepidoptera, Hymenoptera and Diptera. In
      nature, occlusion-derived viruses (ODVs) initiate baculovirus primary infection
      in the midgut epithelium of insect hosts, and this process is largely dependent
      on a number of ODV envelope proteins designated as per os infectivity factors
      (PIFs). Interestingly, PIF homologs are also present in other invertebrate large
      DNA viruses, which is indicative that per os infection is an ancient and
      phylogenetically conserved entry mechanism shared by these viruses. Here, we
      review the advances in the knowledge of the functions of individual PIFs and
      recent discoveries about the PIF complex, and discuss the evolutionary
      implications of PIF homologs in invertebrate DNA viruses. Furthermore, future
      research highlights on the per os infection mechanism are also prospected.

PMID- 28755303
TI  - [Degeneration of the posterior tibial tendon : Established and new concepts].
AB  - BACKGROUND: The most common cause of degeneration of the posterior tibial tendon
      is a congenital valgus deformity of the calcaneus. Other associated pathologies
      are forefoot supination, forefoot abduction and shortening of the gastrocnemius
      muscle. DIAGNOSTICS: Loaded x-rays of the foot in three planes as well as the
      hindfoot alignment view enable evaluation of the axis of the foot under static
      loading conditions. The posterior tibial tendon can be imaged with ultrasound and
      magnetic resonance imaging (MRI). The fatty degeneration of the posterior tibial
      muscle can be identified in MRI. CONSERVATIVE THERAPY: Unloading of the posterior
      tibial tendon can be achieved by orthotics with medial support or braces.
      SURGICAL THERAPY: The surgical therapy of the posterior tibial tendon alone has
      not been proven to be successful. The key element is the correction of the
      hindfoot valgus by medializing calcaneal osteotomy. Depending on the deformity,
      an additional lateral lengthening osteotomy of the calcaneus, as well as a dorsal
      open wedge osteotomy of the medial cuneiform bone (Cotton osteotomy) can
      additionally be indicated. The transposition of the tendon of the flexor
      digitorum longus muscle to the navicular bone is used to augment the posterior
      tibial tendon. Ruptures of the plantar calcaneonavicular ligament are sutured, in
      addition a sinus tarsi spacer can be implanted to protect medial soft tissues. A
      shortening of the gastrocnemius muscle is addressed by release of the
      aponeurosis. First results are published on use of biologically active
      substances, such as platelet rich plasma. RESULTS: The correction of the hindfoot
      deformity as well as the subsequent treatment of the different components of the
      pathology lead to a significant improvement in foot function. Pre-existing
      degenerative alterations are limiting factors.

PMID- 28755304
TI  - Participation of dengue virus NS4B protein in the modulation of immune effectors
      dependent on ER stress in insect cells.
AB  - Organisms' reactions to adverse events result in the generation of immune
      effectors, which, in the case of insects, may be produced from the direct
      activation of pathways such as Toll, Jak-STAT, Imd, or RNAi or may be derived
      from the crosstalk of different intracellular pathways. One such pathway, the
      unfolded protein response (UPR), has the primary objective of restoring
      homeostasis in the endoplasmic reticulum. In addition, the UPR participates in
      signaling crosstalk with the immune pathways, generating protection against
      pathogenic organisms. Dengue virus is a plus-strand RNA virus belonging to the
      Flavivirus genus that uses the ER as a replication site; during the infection,
      there are indicators of the activation of the UPR, which in turn, induces the
      synthesis of internal membranes and preferential translation of viral proteins
      enhancing the replication. One of the dengue virus proteins, the NS4B can block
      the pathway of alpha/beta interferon in mammals. However, what happen in insects
      is interesting because the lack of the main antiviral pathway, the interferon and
      the role of the NS4B protein in the UPR-immunity relationship can be better
      understood. Thus, in this study, we demonstrated that the DENV2/16681 NS4B
      protein is capable of modulating the immune effectors that result from the
      activation of the UPR in insect cells.

PMID- 28755305
TI  - Identification and expression analysis of multiple small heat shock protein genes
      in spruce budworm, Choristoneura fumiferana (L.).
AB  - Fifteen small heat shock protein (sHSP) genes were identified from spruce
      budworm, Choristoneura fumiferana (L.), an important native forest pest in North
      America. The transcript levels of each CfHSP were measured under non-stress
      conditions in all life stages from egg to adult and in five different larval
      tissues. CfHSP transcript levels showed variation during development, with
      highest levels in adults and lowest in eggs. Most CfHSP transcripts are highly
      expressed in larval fat body and Malpighian tubules; two CfHSPs display extremely
      high expression in the head and epidermis. Upon heat stress, nine CfHSP genes are
      significantly upregulated, increasing by 50- to 2500-fold depending on
      developmental stage and tissue type. Upon starvation, eight CfHSPs are
      upregulated or downregulated, whereas six others retain constant expression.
      These results suggest that CfHSPs have important and multiple roles in spruce
      budworm development and in response to heat stress and starvation.

PMID- 28755306
TI  - Keratoconus Treatment Algorithm.
AB  - Keratoconus management has significantly changed over the last two decades. The
      advent of new interventions such as cornea cross-linking, intrastromal corneal
      ring segments, and combined treatments provide corneal clinicians a variety of
      treatment options for the visual rehabilitation of keratoconus patients. This
      review summarizes current evidence for these treatments and highlights their
      place in keratoconus management while new promising emerging therapies are being
      investigated.

PMID- 28755307
TI  - Switch to Semont maneuver is no better than repetition of Epley maneuver in
      treating refractory BPPV.
AB  - : The objectives of this study is to compare the efficacy between repetition of
      Epley maneuver and switch to alternate Semont maneuver in treating posterior
      canal benign paroxysmal positional vertigo (PC-BPPV) that does not respond to the
      initial Epley maneuver. In the nationwide, seven dizziness clinics of Korea, 506
      consecutive patients (303 women, age range 22-87, mean age +/- SD = 64 +/- 12,
      median = 61) with idiopathic PC-BPPV were initially treated with a single Epley
      maneuver. Of those, 144 (28.5%) patients, who did not respond to the therapy,
      were randomized to the repetition of Epley maneuver (n = 70) or switch to Semont
      maneuver (n = 74). The therapeutic efficacy was determined within 1 h by a
      blinded examiner after the trial of each second maneuver. The efficacy did not
      differ between the repetition of Epley maneuver and switch to Semont maneuver
      groups (38.6 vs. 27.0%, p = 0.14, Chi-square test). However, the patients with a
      long duration (p < 0.001, linear regression) and latency (p = 0.01) of the
      positional nystagmus during Dix-Hallpike maneuver showed a higher rate of the
      initial and second treatment failures. Either Epley or Semont maneuver may be
      applied as a second treatment to the patients with PC-BPPV refractory to the
      initial Epley maneuver. This study provides Class I evidence that repeated Epley
      and switch to Semont maneuver shows a similar efficacy in treating PC-BPPV that
      does not respond to the initial Epley maneuver. CLINICAL TRIAL REGISTRATION:
      NCT01822002.

PMID- 28755308
TI  - Effect of Context on the Contribution of Individual Harmonics to Residue Pitch.
AB  - There is evidence that the contribution of a given harmonic in a complex tone to
      residue pitch is influenced by the accuracy with which the frequency of that
      harmonic is encoded. The present study investigated whether listeners adjust the
      weights assigned to individual harmonics based on acquired knowledge of the
      reliability of the frequency estimates of those harmonics. In a two-interval
      forced-choice task, seven listeners indicated which of two 12-harmonic complex
      tones had the higher overall pitch. In context trials (60 % of all trials), the
      fundamental frequency (F0) was 200 Hz in one interval and 200 + DeltaF0 Hz in the
      other. In different (blocked) conditions, either the 3rd or the 4th harmonic
      (plus the 7th, 9th, and 12th harmonics), were replaced by narrowband noises that
      were identical in the two intervals. Feedback was provided. In randomly
      interspersed test trials (40 % of all trials), the fundamental frequency was 200
      + DeltaF0/2 Hz in both intervals; in the second interval, either the third or the
      fourth harmonic was shifted slightly up or down in frequency with equal
      probability. There were no narrowband noises. Feedback was not provided. The
      results showed that substitution of a harmonic by noise in context trials reduced
      the contribution of that harmonic to pitch judgements in the test trials by a
      small but significant amount. This is consistent with the notion that listeners
      give smaller weight to a harmonic or frequency region when they have learned that
      this frequency region does not provide reliable information for a given task.

PMID- 28755309
TI  - Spatial Selectivity in Cochlear Implants: Effects of Asymmetric Waveforms and
      Development of a Single-Point Measure.
AB  - Three experiments studied the extent to which cochlear implant users' spatial
      selectivity can be manipulated using asymmetric waveforms and tested an efficient
      method for comparing spatial selectivity produced by different stimuli.
      Experiment 1 measured forward-masked psychophysical tuning curves (PTCs) for a
      partial tripolar (pTP) probe. Maskers were presented on bipolar pairs separated
      by one unused electrode; waveforms were either symmetric biphasic ("SYM") or
      pseudomonophasic with the short high-amplitude phase being either anodic ("PSA")
      or cathodic ("PSC") on the more apical electrode. For the SYM masker, several
      subjects showed PTCs consistent with a bimodal excitation pattern, with discrete
      excitation peaks on each electrode of the bipolar masker pair. Most subjects
      showed significant differences between the PSA and PSC maskers consistent with
      greater masking by the electrode where the high-amplitude phase was anodic, but
      the pattern differed markedly across subjects. Experiment 2 measured masked
      excitation patterns for a pTP probe and either a monopolar symmetric biphasic
      masker ("MP_SYM") or pTP pseudomonophasic maskers where the short high-amplitude
      phase was either anodic ("TP_PSA") or cathodic ("TP_PSC") on the masker's central
      electrode. Four of the five subjects showed significant differences between the
      masker types, but again the pattern varied markedly across subjects. Because the
      levels of the maskers were chosen to produce the same masking of a probe on the
      same channel as the masker, it was correctly predicted that maskers that produce
      broader masking patterns would sound louder. Experiment 3 exploited this finding
      by using a single-point measure of spread of excitation to reveal significantly
      better spatial selectivity for TP_PSA compared to TP_PSC maskers.

PMID- 28755310
TI  - Core Body Temperature Effects on the Mouse Vestibulo-ocular Reflex.
AB  - Core body temperature has been shown to affect vestibular end-organ and nerve
      afferents so that their resting discharge rate and sensitivity increase with
      temperature. Our aim was to determine whether these changes observed in
      extracellular nerve recordings of anaesthetized C57BL/6 mice corresponded to
      changes in the behavioural vestibulo-ocular reflex (VOR) of alert mice. The VOR
      drives eye rotations to keep images stable on the retina during head movements.
      We measured the VOR gain (eye velocity/head velocity) and phase (delay between
      vestibular stimulus and response) during whole-body sinusoidal rotations ranging
      0.5-12 Hz with peak velocity 50 or 100  degrees /s in nine adult C57BL/6 mice. We
      also measured the VOR during whole-body transient rotations with acceleration
      3000 or 6000  degrees /s2 reaching a plateau of 150 or 300  degrees /s. These
      measures were obtained while the mouse's core body temperature was held at either
      32 or 37  degrees C for at least 35 min before recording. The temperature
      presentation order and timing were pseudo-randomized. We found that a temperature
      increase from 32 to 37  degrees C caused a significant increase in sinusoidal VOR
      gain of 17 % (P < 0.001). Temperature had no other effects on the behavioural
      VOR. Our data suggest that temperature effects on regularly firing afferents best
      correspond to the changes that we observed in the VOR gain.

PMID- 28755311
TI  - Sphingomonas montana sp. nov., isolated from a soil sample from the Tanggula
      Mountain in the Qinghai Tibetan Plateau.
AB  - An orange pigmented, Gram-staining negative, aerobic, motile, rod-shaped
      bacterium isolated from a soil from the Tanggula Mountain, China was studied
      using a polyphasic approach. Based on 16S rRNA gene sequence similarity, strain
      W16RDT was found to be closely related to Sphingomonas prati DSM 103336T (99%),
      Sphingomonas fennica DSM 13665T (97.21%), followed by Sphingomonas laterariae DSM
      25432T (96.44%), Sphingomonas haloaromaticamans CGMCC 1.10206 T (96.36%) and
      Sphingomonas formosensis DSM 24164T (96.06%). The strain was found to be catalase
      and oxidase positive and was found to grow optimally at temperatures of 20-25 
      degrees C, pH 8 and tolerated NaCl concentration up to 1% (w/v). The major fatty
      acids identified were summed feature eight comprising C18:1 omega 7c and/or C18:1
      omega 6c (39.2%), summed feature three comprising of C16:1 omega7c and/or C16:1
      omega6c (36.7%) and C16:0 (7.0%). The polar lipids detected were
      phosphatidylcholine, sphingoglycolipid, phosphatidylglycerol,
      phosphatidylethanolamine, diphosphatidylglycerol,
      phosphatidyldimethylethanolamine, phosphatidylmonomethylethanolamine, and three
      unidentified lipids. The strain possessed ubiquinone-10 (Q-10) as the predominant
      respiratory quinone. Along with other distinguishing characteristics, we also
      describe the draft genome of strain W16RDT. The final assembled draft genome
      sequence is 3,722,743 bp with 3390 coding and 48 RNA (45 tRNA and 3 rRNA) genes.
      The DNA G+C content of the genomic DNA was determined to be 67%. The DNA-DNA
      relatedness value between the strain W16RDT and its closest phylogenetic
      relatives S. prati DSM 103336T, S. fennica DSM 13665T, S. laterariae DSM 25432T,
      and S. haloaromaticamans CGMCC 1.10206T were 52.17, 47.60, 20.93 and 17.09%
      respectively. The strain W16RDT could be distinguished genotypically and
      phenotypically from the recognized species belonging to the genus Sphingomonas
      and thus represents a novel species, for which the name Sphingomonas montana sp.
      nov. is proposed. The type strain is W16RDT (=CGMCC 1.15646T = DSM 103337T).

PMID- 28755312
TI  - Mouse Nudt13 is a Mitochondrial Nudix Hydrolase with NAD(P)H Pyrophosphohydrolase
      Activity.
AB  - The mammalian NUDT13 protein possesses a sequence motif characteristic of the
      NADH pyrophosphohydrolase subfamily of Nudix hydrolases. Due to the persistent
      insolubility of the recombinant product expressed in Escherichia coli, active
      mouse Nudt13 was expressed in insect cells from a baculovirus vector as a
      histidine-tagged recombinant protein. In vitro, it efficiently hydrolysed NADH to
      NMNH and AMP and NADPH to NMNH and 2',5'-ADP and had a marked preference for the
      reduced pyridine nucleotides. Much lower activity was obtained with other
      nucleotide substrates tested. K m and k cat values for NADH were 0.34 mM and 7 s
      1 respectively. Expression of Nudt13 as an N-terminal fusion to green fluorescent
      protein revealed that it was targeted exclusively to mitochondria by the N
      terminal targeting peptide, suggesting that Nudt13 may act to regulate the
      concentration of mitochondrial reduced pyridine nucleotide cofactors and the
      NAD(P)+/NAD(P)H ratio in this organelle and elsewhere. Future studies of the
      enzymology of pyridine nucleotide metabolism in relation to energy homeostasis,
      redox control, free radical production and cellular integrity should consider the
      possible regulatory role of Nudt13.

PMID- 28755313
TI  - Targeting B Cell Signaling in Chronic Lymphocytic Leukemia.
AB  - In recent years, a revolution in the management of chronic lymphocytic leukemia
      (CLL) has centered on the targeting of the B cell receptor (BCR) signaling
      pathway. Our improved understanding of the biology of cell signaling in CLL and
      the development of oral kinase inhibitors directed at the BCR pathway has led to
      the approval of two new agents and has the potential to radically change the
      treatment of CLL in both the relapsed/refractory and upfront settings. In this
      review, we will describe the underlying biology of the BCR signaling pathway. We
      will discuss the landmark clinical trials resulting in the approval of the Bruton
      tyrosine kinase (BTK) inhibitor ibrutinib and the PI3Kdelta inhibitor idelalisib.
      We will highlight ongoing trials that are evaluating the use of combinations of
      these agents with standard chemotherapy. We will evaluate some of the emerging
      data regarding toxicity, potential off-target effects, and mechanisms of
      resistance to BCR signaling pathway blockade. Finally, we will highlight some of
      the next-generation BCR pathway inhibitors currently in development.

PMID- 28755314
TI  - Checkpoint Inhibitors for Non-Small Cell Lung Cancer Among Older Adults.
AB  - Non-small cell lung cancer (NSCLC) is mostly a disease of older adults, with its
      incidence and mortality rates increasing exponentially after the age of 65 years.
      Immune checkpoint inhibitors (ICIs) have changed the scene of NSCLC treatment
      after a long and relatively stagnant period of standard treatment regimens.
      However, little is known about the specific impact of these agents in older
      adults for whom care is often complicated by a variety of syndromes. This
      underlines the importance of understanding the dynamics of new cancer treatments
      in an older patient population. In this paper, we will review ICIs' mechanism of
      action and data from published clinical trials relevant to older adults. In
      addition, we will discuss immune aging and treatment-related toxicity as
      potential challenges facing the use of checkpoint inhibitors in older adults with
      NSCLC.

PMID- 28755316
TI  - Deficiency of a membrane skeletal protein, 4.1G, results in myelin abnormalities
      in the peripheral nervous system.
AB  - We previously demonstrated that a membrane skeletal molecular complex, 4.1G
      membrane palmitoylated protein 6 (MPP6)-cell adhesion molecule 4, is incorporated
      in Schwann cells in the peripheral nervous system (PNS). In this study, we
      evaluated motor activity and myelin ultrastructures in 4.1G-deficient (-/-) mice.
      When suspended by the tail, aged 4.1G-/- mice displayed spastic leg extension,
      especially after overwork. Motor-conduction velocity in 4.1G-/- mice was slower
      than that in wild-type mice. Using electron microscopy, 4.1G-/- mice exhibited
      myelin abnormalities: myelin was thicker in internodes, and attachment of myelin
      tips was distorted in some paranodes. In addition, we found a novel function of
      4.1G for sorting a scaffold protein, Lin7, due to disappearance of the
      immunolocalization and reduction of the production of Lin7c and Lin7a in 4.1G-/-
      sciatic nerves, as well as the interaction of MPP6 and Lin7 with
      immunoprecipitation. Thus, we herein propose 4.1G functions as a signal for
      proper formation of myelin in PNS.

PMID- 28755317
TI  - Early inflammatory profiling of schwannoma cells induced by lipopolysaccharide.
AB  - Inflammatory profiling of Schwann cells manifested as an upregulation of
      cytokines is present after traumatic or disease injury of the peripheral nerves.
      Inflammatory activation of Schwann cells via Toll-like receptors (TLRs) can be
      triggered by exogenous pathological molecules or endogenous ligands produced
      during Wallerian degeneration. We investigated the early period of inflammatory
      reactions by following the levels of TLR4, NFkappaB, IL-1beta, pSTAT3, and IL-6
      proteins after LPS treatment of RT4 schwannoma cells under in vitro conditions.
      Significantly increased levels of NFkappaB, IL-1beta, pSTAT3, and IL-6 proteins
      were found 1 h after LPS action indicating their involvement in the initiation of
      the inflammatory reaction of schwannoma cells. This initiation was induced
      without increased TLR4 protein expression, but was accompanied by the appearance
      of TLR4 in early endosomes. The protein levels decreased within the next 6 h of
      treatment with a subsequent increase of NFkappaB, IL-1beta, and pSTAT3 after 24 h
      of LPS treatment. In contrast, continuous decrease of IL-6 over time following
      LPS treatment was unexpected. Levels of soluble IL-6 protein in the culture
      medium also decreased with decreasing levels of LPS over 24 h.

PMID- 28755318
TI  - Characterization of the biodegradation, bioremediation and detoxification
      capacity of a bacterial consortium able to degrade the fungicide thiabendazole.
AB  - Thiabendazole (TBZ) is a persistent fungicide used in the post-harvest treatment
      of fruits. Its application results in the production of contaminated effluents
      which should be treated before their environmental discharge. In the absence of
      efficient treatment methods in place, biological systems based on microbial
      inocula with specialized degrading capacities against TBZ could be a feasible
      treatment approach. Only recently the first bacterial consortium able to rapidly
      transform TBZ was isolated. This study aimed to characterize its biodegradation,
      bioremediation and detoxification potential. The capacity of the consortium to
      mineralize 14C-benzyl-ring labelled TBZ was initially assessed. Subsequent tests
      evaluated its degradation capacity under various conditions (range of pH,
      temperatures and TBZ concentration levels) and relevant practical scenarios
      (simultaneous presence of other postharvest compounds) and its bioaugmentation
      potential in soils contaminated with increasing TBZ levels. Finally cytotoxicity
      assays explored its detoxification potential. The consortium effectively
      mineralized the benzoyl ring of the benzimidazole moiety of TBZ and degraded
      spillage level concentrations of the fungicide in aqueous cultures (750 mg L-1)
      and in soil (500 mg kg-1). It maintained its high degradation capacity in a wide
      range of pH (4.5-7.5) and temperatures (15-37  degrees C) and in the presence of
      other pesticides (ortho-phenylphenol and diphenylamine). Toxicity assays using
      the human liver cancer cell line HepG2 showed a progressive decrease in
      cytotoxicity, concomitantly with the biodegradation of TBZ, pointing to a
      detoxification process. Overall, the bacterial consortium showed high potential
      for future implementation in bioremediation and biodepuration applications.

PMID- 28755319
TI  - A novel family of proline/serine-rich proteins, which are phospho-targets of
      stress-related mitogen-activated protein kinases, differentially regulates growth
      and pathogen defense in Arabidopsis thaliana.
AB  - The molecular actions of mitogen-activated protein kinases (MAPKs) are ultimately
      accomplished by the substrate proteins where phosphorylation affects their
      molecular properties and function(s), but knowledge regarding plant MAPK
      substrates is currently still fragmentary. Here, we uncovered a previously
      uncharacterized protein family consisting of three proline/serine-rich proteins
      (PRPs) that are substrates of stress-related MAPKs. We demonstrated the
      importance of a MAPK docking domain necessary for protein-protein interaction
      with MAPKs and consequently also for phosphorylation. The main phosphorylated
      site was mapped to a residue conserved between all three proteins, which when
      mutated to a non-phosphorylatable form, differentially affected their protein
      stability. Together with their distinct gene expression patterns, this
      differential accumulation of the three proteins upon phosphorylation probably
      contributes to their distinct function(s). Transgenic over-expression of PRP, the
      founding member, led to plants with enhanced resistance to Pseudomonas syringae
      pv. tomato DC3000. Older plants of the over-expressing lines have curly leaves
      and were generally smaller in stature. This growth phenotype was lost in plants
      expressing the phosphosite variant, suggesting a phosphorylation-dependent
      effect. Thus, this novel family of PRPs may be involved in MAPK regulation of
      plant development and / or pathogen resistance responses. As datamining
      associates PRP expression profiles with hypoxia or oxidative stress and PRP
      overexpressing plants have elevated levels of reactive oxygen species, PRP may
      connect MAPK and oxidative stress signaling.

PMID- 28755320
TI  - Evaluation of the mature grain phytase candidate HvPAPhy_a gene in barley
      (Hordeum vulgare L.) using CRISPR/Cas9 and TALENs.
AB  - In the present study, we utilized TALEN- and CRISPR/Cas9-induced mutations to
      analyze the promoter of the barley phytase gene HvPAPhy_a. The purpose of the
      study was dual, validation of the PAPhy_a enzyme as the main contributor of the
      mature grain phytase activity (MGPA), as well as validating the importance of a
      specific promoter region of the PAPhy_a gene which contains three overlapping cis
      acting regulatory elements (GCN4, Skn1 and the RY-element) known to be involved
      in gene expression during grain filling. The results confirm that the barley
      PAPhy_a enzyme is the main contributor to the MGPA as grains of knock-out lines
      show very low MGPA. Additionally, the analysis of the HvPAPhy_a promoter region
      containing the GCN4/Skn1/RY motif highlights its importance for HvPAPhy_a
      expression as the MGPA in grains of plant lines with mutations within this motif
      is significantly reduced. Interestingly, lines with deletions located downstream
      of the motif show even lower MGPA levels, indicating that the GCN4/SKn1/RY motif
      is not the only element responsible for the level of PAPhy_a expression during
      grain maturation. Mutant grains with very low MPGA showed delayed germination as
      compared to grains of wild type barley. As grains with high levels of preformed
      phytases would provide more readily available phosphorous needed for a fast
      germination, this indicates that faster germination may be implicated in the
      positive selection of the ancient PAPhy gene duplication that lead to the
      creation of the PAPhy_a gene.

PMID- 28755321
TI  - Prophylactic anticonvulsants in patients with primary glioblastoma.
AB  - Glioblastoma is the most common form of primary brain cancer in adults and one of
      the deadliest of human cancers. Seizures are one of the most frequent
      presentations of glioblastoma. The use of anti-epileptic drugs (AEDs) in
      glioblastoma patients suffering from seizures is well accepted. However, the role
      of long-term AED use in patients with glioblastoma without a history of seizures
      is controversial. Here, we performed a review of the literature to identify
      studies that examined the use of AEDs in seizure-free glioblastoma patients. We
      identified one randomized controlled study suggesting no clinical benefit of
      seizure prophylaxis in this population. Three of the four retrospective studies
      identified in our search recapitulated this finding, while the remaining study
      suggested a benefit for prophylactic AED use. All identified studies were focused
      on seizure incidence in the post-operative period, ranging from 1 week to long
      term follow up. Implications of these findings are reviewed herein.

PMID- 28755322
TI  - Extraneuraxial metastases in medulloblastoma: is histology and molecular biology
      important?

PMID- 28755323
TI  - Detection of the alternative lengthening of telomeres pathway in malignant
      gliomas for improved molecular diagnosis.
AB  - Human malignant gliomas exhibit acquisition of either one of two telomere
      maintenance mechanisms, resulting from either reactivation of telomerase
      expression or activation of an alternative lengthening of telomeres (ALT)
      mechanism. In the present study, we analyzed 63 human malignant gliomas for the
      presence of ALT-specific extrachromosomal circles of telomeric DNA (C-circles)
      and measured telomerase expression, telomeric DNA content (Telo/Alu method), and
      telomeric repeat-containing RNAs (TERRA) levels. We also assessed histomolecular
      markers routinely used in clinical practice. The presence of C-circles
      significantly correlated with IDH1/2 mutation, MGMT exon 1 methylation, low Ki-67
      immunostaining, increased telomeric DNA content, absence of functional ATRX
      protein and level of HTERT gene expression. In multivariate analysis, we observed
      a trend to a correlation between elevated TERRA levels and increased survival.
      Interestingly, the C-circles assay allowed to detect ALT activation in
      glioblastomas exhibiting wild-type IDH1/2 and ATRX expression. These results
      suggest that, after the correlations uncovered here have been confirmed on larger
      numbers of tumors, telomeric markers might be useful in improving diagnosis. They
      also point out to the utility of using the specific, sensitive and quantitative C
      circle and Telo/Alu assays that can work with as few as 30 ng of tumor DNA.

PMID- 28755324
TI  - Volumetric quantification of glioblastoma: experiences with different measurement
      techniques and impact on survival.
AB  - The potential impact of different radiological features of glioblastoma
      multiforme (GBM) on overall survival (OS) like tumor volume, peritumoral edema
      (PTE), necrosis volume, necrosis-tumor ratio (NTR) and edema-tumor ratio (ETR) is
      still very controversial. To determine the influence of volumetric data on OS und
      to compare different measuring techniques described in literature. We
      prospectively evaluated preoperative MR images from 30 patients harboring a
      primary supratentorial GBM. All patients received gross-total tumor resection
      followed by standard radiation and chemotherapy (temozolomide). By 3D semi
      automated segmentation, we measured tumor volume, necrosis volume, PTE,
      postoperative residual tumor volume and calculated ETR, NTR and the extent of
      resection. After critical review of the existing literature we compared
      alternative measuring techniques with the gold standard of 3D segmentation.
      Statistical analysis showed a significant impact of the preoperative tumor and
      necrosis volumes on OS (p = 0.041, respectively p = 0.039). Furthermore, NTR also
      showed a significant association with OS (p = 0.005). Comparison of previously
      described measuring techniques and scorings with our results showed that no other
      technique is reliable and accurate enough as a predictive tool. The critical
      review of previously published studies revealed mainly inaccurate measurement
      techniques and patient selection as potential reasons for inconsistent results.
      Preoperatively measured necrosis volume and NTR are the most important
      radiological features of GBM with a strong influence on OS. No other measuring
      techniques are specific enough and comparable with 3D segmentation.

PMID- 28755325
TI  - Women's Experiences of Childbirth in Serbian Public Healthcare Institutions: a
      Qualitative Study.
AB  - PURPOSE: The aim of the present study was to explore how women, users of public
      maternity healthcare services in Serbia, experience birth and what the most
      problematic relational aspects of institutional context associated with negative
      or even traumatic aspects of birth experiences are, as described by the women
      themselves. METHOD: An exploratory qualitative study was undertaken using semi
      structured interviews with 15 primiparous women aged 26 to 49 who have recently
      given birth in different public healthcare institutions in Belgrade. The basic
      framework for the analysis of interview transcripts was the interpretative
      phenomenological analysis (IPA). RESULTS: Through the analysis, four relatively
      broad and partly interrelated themes emerged: (a) feelings of isolation and
      abandonment, (b) lack of communication, (c) lack of a caring relationship, and
      (d) lack of control and agency. The aspects of institutional environment that
      were considered particularly distressing in most of the childbirth experiences
      are related to distant and cold relationship with healthcare providers which adds
      to the feelings of isolation and abandonment, in addition to the lack of insight
      into and control over the process of birth that is managed in the hospital
      context without relying on women's subjective involvement in any relevant way.
      CONCLUSION: The present study emphasized a supportive and caring relationship
      with medical practitioners, as well as allowing women to be more involved into
      their birthing process, as crucial for positive experience of birth, which might
      have profound and long-lasting psychosocial consequences. Recommendations for
      policy makers and future research are offered.

PMID- 28755326
TI  - A Pilot Randomized Controlled Trial of an Internet-Based Alcohol Intervention in
      a Workplace Setting.
AB  - PURPOSE: The aim of this study was to compare the effectiveness of a brief and an
      intensive self-help alcohol intervention and to assess the feasibility of
      recruiting to such interventions in a workplace setting. METHOD: Employees who
      screened positive for hazardous drinking (n = 85) received online personalized
      normative feedback and were randomly assigned to one out of two conditions:
      either they received an e-booklet about the effects of alcohol or they received a
      self-help intervention comprising 62 web-based, fully automated, and interactive
      sessions, plus reminder e-mails, and mobile phone text messages (Short Message
      Service). RESULTS: Two months after baseline, the responders in the intensive
      condition drank an average of five to six drinks less per week compared to the
      responders in the brief condition (B = 5.68, 95% CI = 0.48-10.87, P = .03). There
      was no significant difference between conditions, using baseline observation
      carried forward imputation (B = 2.96, 95% CI = -0.50-6.42, P = .09). Six months
      after baseline, no significant difference was found, neither based on complete
      cases nor intent-to-treat (B = 1.07, 95% CI = -1.29-3.44, P = .37). Challenges
      with recruitment are thoroughly reported. CONCLUSION: The study supports the
      feasibility and the safety of use for both brief and intensive Internet-based
      self-help in an occupational setting. The study may inform future trials, but due
      to recruitment problems and low statistical power, the findings are inconclusive
      in terms of the intensive program being more effective than brief intervention
      alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01931618.

PMID- 28755327
TI  - Comorbidities and intensity-modulated radiotherapy with simultaneous integrated
      boost in elderly breast cancer patients.
AB  - PURPOSE: To evaluate the impact of comorbidity assessment on compliance to
      intensity modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) in
      elderly patients affected by early stage breast cancer (BC). MATERIALS AND
      METHODS: 40 consecutive patients were treated with SIB-IMRT (50 Gy in 25
      fractions to the whole breast, and simultaneously 60 Gy to the surgical bed) for
      invasive BC after conserving surgery. Inclusion criteria were: age >= 70 years,
      pT1-2 disease, pN0-1, no neoadjuvant chemotherapy, non-metastatic disease.
      Charlson comorbidity index was used for comorbidity evaluation. RESULTS: Median
      follow-up was 44 months. At the time of the analysis, OS and LC rates were 100%.
      All patients completed the SIB-IMRT without interruptions. Acute skin toxicity
      was recorded as follows: grade 0 in 5 patients (12.5%), grade 1 in 25 cases
      (62.5%), and grade 2 in 10 patients (25%). Regarding late adverse events, skin
      toxicity was registered as follows: grade 0 in 27 patients (67.5%) and grade 1 in
      13 cases (32.5%). No toxicity >=grade 2 was registered. At statistical analysis,
      the presence of comorbidities and the breast volume >700 cc were related to skin
      grade 2 acute toxicity (p = 0.01, p = 0.04). In terms of cosmetic results, 98 and
      2% of patients considered the result as good/excellent and as fair after RT,
      respectively. No patients had a poor cosmetic outcome. CONCLUSION: The present
      study showed the feasibility of SIB-IMRT in early stage BC elderly patients and
      that the absence of comorbidity reduced the risk of acute radiation toxicity.

PMID- 28755328
TI  - Alternaria toxins in South African sunflower seeds: cooperative study.
AB  - Sunflower seed samples (N = 80) from different sunflower cultivars originating
      from different localities in South Africa were analyzed for 15 toxins produced by
      fungi of the genus Alternaria by means of a simple one-step extraction dilute-and
      shoot HPLC-MS/MS approach. References for valine-tenuazonic acid (Val-TeA),
      altenusin (ALTS), and altenuisol (ALTSOH) were isolated from fungal culture
      extracts and spectroscopically characterized. Additionally, valine-tenuazonic
      acid was tested regarding its cytotoxicity in comparison with tenuazonic acid
      (TeA) and showed less activity on HT-29 cells. Furthermore, alternariol
      monomethyl ether-3-O-beta-D-glucoside (AME-3G) was produced by fermentation of
      alternariol monomethyl ether (AME) with the fungus Rhizopus oryzae. The seed
      samples were analyzed both with and without hulls. The method covers the AAL
      toxins TA1 and TA2, altenuene (ALT) and iso-altenuene (iso-ALT), altenuisol,
      altenusin, altertoxin I (ATX-I) and altertoxin II (ATX-II), alternariol (AOH) and
      alternariol monomethyl ether, alternariol monomethyl ether-3-O-beta-D-glucoside,
      tenuazonic acid, allo-tenuazonic acid (allo-TeA) and valine-tenuazonic acid, and
      tentoxin (TEN). More than 80% of the samples were positive for one or more
      analytes above the respective limit of detection (0.2-23 MUg/kg). Alternariol,
      its monomethyl ether, tentoxin, tenuazonic acid, altenuisol, and valine
      tenuazonic acid were found in quantifiable amounts. The highest prevalences were
      found for tentoxin (73% positive, mean content 13.2 MUg/kg, maximum level 130 +/-
      0.9 MUg/kg) followed by tenuazonic acid (51% positive, mean content 630 MUg/kg,
      maximum level 6300 +/- 560 MUg/kg). The obtained data were further analyzed
      statistically to identify quantitative or qualitative relationships between the
      levels of Alternaria toxin in the samples.

PMID- 28755330
TI  - A critical appraisal of the quality of adult musculoskeletal ultrasound
      guidelines using the AGREE II tool: an EuroAIM initiative.
AB  - OBJECTIVES: Our aim was to evaluate the quality of published guidelines on
      musculoskeletal ultrasound (MSK-US) for adults. METHODS: Between June and July
      2016, we conducted an online search for MSK-US guidelines, which were evaluated
      by four independent readers blinded to each other using the AGREE II tool. A
      fifth independent reviewer calculated scores per each domain and agreement
      between reviewers' scores using the intraclass correlation coefficient (ICC).
      RESULTS: Five guidelines were included in this appraisal. They were published
      between 2001 and 2014. Our appraisal showed intermediate results, with four out
      of five guidelines scoring "average" as overall quality. Domain 1 (scope and
      purpose) achieved the highest result (total score = 71.1% +/- 18.7%). Domain 6
      (editorial independence) had the lowest score (total score = 26.3% +/- 19.3%).
      Interobserver agreement was very good for all the evaluated guidelines (ICC
      ranged between 0.932 and 0.956). CONCLUSIONS: Overall, quality of MSK-US
      guidelines ranges from low to average when evaluated using the AGREE II tool. The
      editorial independence domain was the most critical, thus deserving more
      attention when developing future guidelines. MAIN MESSAGES: * Four of five
      guidelines on MSK-US had an average quality level. * Scope/purpose had the
      highest score (71.1% +/- 18.7%). * Editorial independence had the lowest score
      (26.3% +/- 19.3%). * Interobserver agreement was very good (ranges: 0.932-0.956).

PMID- 28755329
TI  - Brain Tumor-Related Epilepsy: a Current Review of the Etiologic Basis and
      Diagnostic and Treatment Approaches.
AB  - PURPOSE OF REVIEW: The relationship of brain tumors and seizures remains poorly
      understood. This article is an overview of the epidemiology, etiology, and
      diagnostic and treatment approaches of tumor-related epilepsy primarily with
      regard to glial-based tumors, the most commonly considered brain tumor in this
      field. RECENT FINDINGS: Over the past many years, several novel etiologic
      mechanisms to explain how tumors induce seizures have been developed, which this
      article reviews, including the roles of glutamate-induced excitotoxicity, matrix
      metalloproteinases, isocitrate dehydrogenase, methylguanine methyltransferase,
      and functional network connectivity. As well, diagnostic and treatment approaches
      vary considerably. This article summarizes the evidence and provides the
      rationale for a reconsideration of how we deliver pre-operative, peri-operative,
      and post-operative care to these patients. Patients with brain tumors and
      epilepsy are a very challenging subgroup of patients, which necessitates not just
      a thorough understanding of the current principles regarding tumor-related
      epilepsy but also the development of collaborative research to advance our
      knowledge even further, and a concerted effort to develop a standardized, multi
      disciplinary clinical approach to improve the care of these patients.

PMID- 28755331
TI  - Cultivar-Dependent Direct Organogenesis of Date Palm from Shoot Tip Explants.
AB  - A number of public and private laboratories are working on date palm
      micropropagation to meet the increasing worldwide demand for date palm planting
      material. A standardized direct organogenesis protocol exists for the production
      of date palm plantlets to maintain the genetic fidelity of regenerated plants.
      Organogenesis has the advantage of using low concentrations of plant growth
      regulators and avoiding the callus phase. In addition, direct regeneration of
      vegetative buds minimizes the risk of somaclonal variation among plant
      regenerants. However, in vitro multiplication cycles should be limited in
      duration by frequent renewal of plant material. This chapter describes a simple
      and routine organogenesis protocol for date palm multiplication using shoot tip
      explants.

PMID- 28755332
TI  - NAA-Induced Direct Organogenesis from Female Immature Inflorescence Explants of
      Date Palm.
AB  - Micropropagation has great potential for the multiplication of female and male
      date palms of commercially grown cultivars by using inflorescences. This approach
      is simple, convenient, and much faster than the conventional method of using
      shoot-tip explants. We describe here a stepwise micropropagation procedure using
      inflorescence explants of Iraqi date palm cultivar Maktoom. Cultured explants
      were derived from 0.5-cm-long spike segments excised from 8 to 10-cm-long
      spathes. About 70% formed adventitious buds on Murashige and Skoog (MS) medium
      supplemented with 2 mg/L naphthalene acetic acid (NAA), 4 mg/L benzylaminopurine
      (BAP), and 40 g/L sucrose and maintained in the dark for 16 weeks before
      transferring to normal light conditions. The best multiplication rate was
      achieved with 3 mg/L 2ip and 2 mg/L; for shoot elongation, the best medium is MS
      containing 0.5 mg/L BAP, 0.5 mg/L 2ip, and 1 mg/L GA3. Well-developed shoots were
      cultured for rooting in half MS medium amended with 1 mg/L NAA and 45 g/L
      sucrose. Plantlets with well-developed roots were successfully hardened in the
      greenhouse. Inflorescence explants proved to be a promising alternative explant
      source for micropropagation of date palm cultivars.

PMID- 28755333
TI  - Direct Organogenesis from Immature Female Inflorescence of Date Palm by Gradual
      Reduction of 2,4-D Concentration.
AB  - Inflorescences represent an alternative explant source for superior date palm
      trees, especially those that do not produce offshoots. They provide large numbers
      of explants free of fungal and bacterial contamination for successful tissue
      culture initiation. Furthermore, they are characterized by the capacity of plant
      regeneration within a short time as compared to other explant types. This chapter
      focuses on the procedures employed for plant regeneration by direct organogenesis
      using immature female inflorescence explants, including initiation of
      adventitious buds, differentiation, multiplication, shoot elongation, rooting,
      and acclimatization. Adding 5 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) into
      the initiation medium and gradually reducing it to 1 and then to 0.5 mg/L in the
      subsequent 2 subcultures, respectively, are determining factors in direct
      adventitious bud formation from the inflorescence. Bud differentiation is
      obtained on MS medium containing 0.25 mg/L kinetin (Kin), 0.25 mg/L benzyladenine
      (BA), 0.25 mg/L abscisic acid (ABA), 0.1 mg/L naphthaleneacetic acid (NAA), and
      0.2 g/L activated charcoal (AC). Regenerated shoots exhibit sufficient root
      formation on MS medium supplemented with 2 mg/L indole butyric acid (IBA) and 1
      mg/L NAA and subsequent survival in the greenhouse.

PMID- 28755334
TI  - Optimized Direct Organogenesis from Shoot Tip Explants of Date Palm.
AB  - In vitro propagation is an available alternative to produce uniform and good
      quality planting material to establish large-scale date palm cultivation in a
      short time. This study was carried out to achieve organogenesis and
      multiplication directly from shoot tips without callus formation, thus avoiding
      any possibility of undesirable genetic variability among the regenerated plants.
      The shoot tips explants are cultured on Murashige and Skoog (MS) medium
      supplemented with 1 mg/L naphthaleneacetic acid (NAA), 1 mg/L naphthoxyacetic
      acid (NOA), 2.5 mg/L benzyladenine (BA), and 2.5 mg/L isopentenyladenine (2iP).
      Numerous adventitious buds appeared from the shoot tip explants in darkness after
      six subcultures at 4-week intervals. Vegetative buds pass through three stages:
      initiation bud formation, vegetative bud differentiation, and shoot bud
      proliferation. Shoots are transferred onto medium containing low concentrations
      of growth regulators for shoot multiplication. The organogenesis protocol
      described herein consists of six steps: initiation of meristematic buds,
      multiplication, elongation, rooting, pre-acclimatization, and finally plant
      acclimatization.

PMID- 28755335
TI  - Direct Organogenesis and Indirect Somatic Embryogenesis by In Vitro Reversion of
      Mature Female Floral Buds to a Vegetative State.
AB  - This protocol describes in vitro plant regeneration from mature female
      inflorescence explants of date palm (Phoenix dactylifera L.) by reversion of
      floral state (reproductive phase) to the vegetative state. The mature female
      inflorescence (fully developed) is cultured on MS induction medium containing 10
      mg/L 2,4-dichlorophenoxyacetic acid (2,4-D), 3 mg/L 2-isopentenyladenine (2iP),
      and 2 mg/L paclobutrazol (PBZ) or 2 mg/L abscisic acid (ABA). The basal part of
      the petals has meristematic cells, which can be induced to initiate callus or
      direct shoot formation depending on the plant growth regulator amendments. Callus
      forms on the induction medium supplemented with PBZ after 12 weeks, whereas it
      differentiates into somatic embryos on a medium containing 0.1 mg/L
      naphthaleneacetic acid (NAA). Direct shoots are regenerated on the induction
      medium amended with ABA after 24 weeks. Procedures for plant regeneration from
      mature female inflorescence explants are described, and histological changes
      which occur during the reversion process are presented.

PMID- 28755336
TI  - Enhanced Indirect Somatic Embryogenesis of Date Palm Using Low Levels of
      Seawater.
AB  - Date palm tolerates salinity, drought, and high temperatures. Arid and semiarid
      zones, especially the Middle East region, need a huge number of date palms for
      cultivation. To meet this demand, tissue culture techniques have great potential
      for mass production of plantlets, especially using the indirect embryogenesis
      technique; any improvement of these techniques is a worthy objective. Low levels
      of salinity can enhance growth and development of tolerant plants. A low level of
      seawater, a natural source of salinity, reduces the time required for
      micropropagation processes of date palm cv. Malkaby when added to MS medium.
      Medium containing seawater at 500 ppm total dissolved solid (TDS) (12.2 mL/L)
      improves callus proliferation, whereas 1500 ppm (36.59 mL/L) enhances plant
      regeneration including multiplication of secondary embryos, embryo germination,
      and rooting.

PMID- 28755337
TI  - Enhanced Indirect Somatic Embryogenesis from Shoot-Tip Explants of Date Palm by
      Gradual Reductions of 2,4-D Concentration.
AB  - Shoot-tip explants obtained from offshoots of adult date palms are an excellent
      source for callus induction and subsequent somatic embryogenesis. In this
      protocol, the shoot-tip explants are transferred sequentially to a series of
      media containing gradually reduced concentrations of plant growth hormones: (a)
      10 mg/L 2,4-dichlorophenoxy acetic acid (2,4-D) and 3 mg/L 2-isopentenyl adenine
      (2iP), (b) 7 mg/L 2,4-D and 1 mg/L 2iP, (c) 5 mg/L 2,4-D and 1 mg/L 2iP, and (d)
      3 mg/L 2,4-D and 1 mg/L 2iP. Embryogenic callus differentiates into somatic
      embryos upon transfer to MS medium containing 0.5 mg/L abscisic acid (ABA) and
      0.1 mg/L naphthalene acetic acid (NAA). Well-matured somatic embryos germinate on
      a medium containing 0.1 mg/L NAA. Repeated, multiple, and secondary somatic
      embryos are induced to produce normal well-developed somatic embryos upon
      transfer to MS medium containing 0.1 mg/L NAA and 0.05 mg/L benzyladenine (BA).
      This protocol is potentially applicable for commercial micropropagation of date
      palm.

PMID- 28755338
TI  - Indirect Somatic Embryogenesis from Mature Inflorescence Explants of Date Palm.
AB  - Due to the limitations associated with shoot tip explants in the micropropagation
      of date palm, inflorescence explants are an ideal alternative. This chapter
      focuses on the protocol for the induction of callus from inflorescence tissue,
      establishment for proliferation of somatic embryos, germination, elongation,
      rooting, and acclimatization. Female inflorescences, 30-40 cm in length, cv.
      Shaishee, were used for culture initiation. After disinfection, the outer
      inflorescence cover (spathe) is cut open, and the spikelet explants, 1 cm long,
      are cultured on modified Murashige and Skoog (MS) medium containing 100 mg/L 2,4
      D, 3 mg/L kinetin, and 3 mg/L 2ip and incubated at 25 +/- 2  degrees C in the
      dark. Callus obtained after 6-8 months of culturing is transferred to the culture
      medium to induce somatic embryogenesis and plant regeneration. Well-developed
      regenerated shoots are cultured on MS medium containing 0.2 mg/L NAA for root
      induction and plantlets acclimatized in the greenhouse before transfer to the
      field.

PMID- 28755339
TI  - Indirect Somatic Embryogenesis of Date Palm Using Juvenile Leaf Explants and Low
      2,4-D Concentration.
AB  - This chapter describes an efficient protocol for large-scale micropropagation of
      date palm. Somatic embryo-derived plants are regenerated from highly
      proliferating suspension cultures. Friable embryogenic callus is initiated from
      juvenile leaves using slightly modified Murashige and Skoog (MS) medium
      supplemented with 0.1 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D). Suspension
      cultures consisting of proembryonic masses are established from highly competent
      callus for somatic embryogenesis using half-strength MS medium enriched with 0.1
      mg/L 2,4-D and 300 mg/L activated charcoal. The productivity of cultures
      increased 20-fold when embryogenic cell suspensions were used instead of standard
      protocols on solidified media. The overall production of somatic embryos mostly
      exceeds 10,000 units per liter per month. Partial desiccation of mature somatic
      embryos, corresponding to a decrease in water content from 90 down to 75%,
      significantly improved germination rates.

PMID- 28755340
TI  - Desiccation-Enhanced Maturation and Germination of Date Palm Somatic Embryos
      Derived from Cell Suspension Culture.
AB  - In vitro plant regeneration via somatic embryogenesis is a powerful tool for
      rapid, large-scale production of healthy true-to-type plants. This approach is
      suitable to preserve existing natural genetic variability and propagation of
      variability generated from genetic improvement programs, including crossing,
      somaclonal variation, mutagenesis, and somatic hybridization. This chapter
      outlines a simplified protocol for date palm regeneration via somatic
      embryogenesis induced in cell suspension cultures. In this protocol, culture
      medium composition is manipulated, including plant growth regulators and solid
      (addition of agar) and liquid media to achieve reduction of production cycle of
      somatic embryogenesis, which increases the multiplication rate of embryogenic
      callus and improves the quantity and quality of somatic embryos.

PMID- 28755341
TI  - Desiccation and Cold Hardening of Date Palm Somatic Embryos Improve Germination.
AB  - Embryogenic suspension cultures of date palm are ideal for mass propagation of
      somatic embryos; however, the low percentage of germination of somatic embryos
      (SE) remains an impediment. This chapter focuses on two important physical
      factors to improve germination of date palm somatic embryos: the use of partial
      desiccation (3 h) of somatic embryos and the exposure to low temperature (4 
      degrees C for 24 h). High germination percentage (41%) is achieved by desiccation
      for 3 h. Moreover, adding 0.3 g/L activated charcoal (AC) to the liquid medium
      further improves somatic embryo number and weight as well as the percentage of
      germination. Moreover, partial desiccation and low temperature exposure tend to
      increase proline content. This improved protocol for somatic embryo germination
      is potentially applicable for commercial micropropagation of date palm.

PMID- 28755342
TI  - Histological Evidence of Indirect Somatic Embryogenesis from Immature Female Date
      Palm Inflorescences.
AB  - Rapid production of somatic embryogenesis and date palm regeneration is achieved
      by culturing immature female inflorescence explants. Inflorescence explants are
      soft, creamy in color, average 6-7 cm in length, and cultured on Murashige and
      Skoog (MS) medium containing 1 mg/L thidiazuron (TDZ). Callus induction occurs
      after 4-5 weeks of culture on the callus induction medium. Subsequently, callus
      develops embryogenic calli on MS medium supplemented with 0.1 mg/L naphthalene
      acetic acid (NAA). Histological samples were collected successively at the
      culturing time and during morphogenetic changes throughout the developmental
      stages of somatic embryos. Initiation of callus and different successive
      developmental stages for somatic embryos including two-celled, four-celled,
      globular, bipolar, and fully developed cotyledonary somatic embryos were
      observed. Mature somatic embryos develop within 10-12 weeks after culture
      establishment.

PMID- 28755343
TI  - Histological Analysis of the Developmental Stages of Direct Somatic Embryogenesis
      Induced from In Vitro Leaf Explants of Date Palm.
AB  - Somatic embryogenesis is an ideal technique for the micropropagation of date palm
      using different explant tissue; however, histological studies describing the
      ontogenesis of plant regeneration are limited. This chapter provides a simple
      protocol for the histological analysis of the successive developmental stages of
      direct somatic embryogenesis induced from in vitro leaf explants. Direct somatic
      embryos are obtained from Murashige and Skoog (MS) medium containing 2 mg/L 6
      benzylaminopurine. In order to observe the different developmental stages,
      histological analysis is carried out on samples at 15-day intervals for 60 days.
      Samples are fixed in formalin acetic alcohol and embedded in paraffin wax. Stain
      serial transverse and longitudinal sections, 8 MUm thick, are stained with
      safranin-Fast Green. After 15 days on the induction medium, somatic embryos
      exhibit multicellular origin directly from the procambium cells, whereas the
      mesophyll and the epidermal cells are not involved in this process. After 2
      months, several developmental stages (pre-globular, globular, early bipolar,
      bipolar, and cotyledonary-shaped) are observed. These embryos germinate after
      transferring to MS medium without plant growth regulators and rooting on 2 mg/L
      NAA-containing medium resulting in complete plantlets.

PMID- 28755344
TI  - Identifying and Controlling Contamination of Date Palm Tissue Cultures.
AB  - Fungal and bacterial contaminations are major problems facing in vitro date palm
      (Phoenix dactylifera L.) proliferation. To overcome this problem, we must first
      identify the fungal (e.g., Alternaria sp., Aspergillus niger, Penicillium sp.)
      and bacterial (e.g., Pseudomonas sp.) spread in date palm in vitro cultures.
      Incorporating fungicides (e.g., copper oxychloride, Vitavax T, and Topsin M) or
      antibiotics (e.g., streptomycin, Banocin, and Bencid D) at 500 mg/L in medium
      significantly reduces the contamination rate during various stages of in vitro
      date palm culture. Streptomyces chloramphenicol (pharmacy) is highly effective in
      reducing the bacterial contamination of date palm cultures to below 10%, as well
      as enhancing growth vigor.

PMID- 28755345
TI  - Controlling Hyperhydricity in Date Palm In Vitro Culture by Reduced Concentration
      of Nitrate Nutrients.
AB  - Hyperhydricity (or vitrification) is a fundamental physiological disorder in date
      palm micropropagation. Several factors have been ascribed as being responsible
      for hyperhydricity, which are related to the explant, medium, culture vessel, and
      environment. The optimization of inorganic nutrients in the culture medium
      improves in vitro growth and morphogenesis, in addition to controlling
      hyperhydricity. This chapter describes a protocol for controlling hyperhydricity
      during the embryogenic callus stage by optimizing the ratio of nitrogen salts of
      the Murashige and Skoog (MS) nutrient culture medium. The best results of
      differentiation from cured hyperhydric callus are obtained using modification at
      a ratio of NH4+/NO3- at 10:15 (825:1425 mg/L) of the MS culture medium to remedy
      hyperhydric date palm callus and achieve the recovery of normal embryogenic
      callus and subsequent regeneration of plantlets. Based on the results of this
      study, nutrient medium composition has an important role in avoiding
      hyperhydricity problems during date palm micropropagation.

PMID- 28755346
TI  - Improvement of In Vitro Date Palm Plantlet Acclimatization Rate with Kinetin and
      Hoagland Solution.
AB  - In vitro propagation of date palm Phoenix dactylifera L. is an ideal method to
      produce large numbers of healthy plants with specific characteristics and has the
      ability to transfer plantlets to ex vitro conditions at low cost and with a high
      survival rate. This chapter describes optimized acclimatization procedures for in
      vitro date palm plantlets. Primarily, the protocol presents the use of kinetin
      and Hoagland solution to enhance the growth of Barhee cv. plantlets in the
      greenhouse at two stages of acclimatization and the appropriate planting medium
      under shade and sunlight in the nursery. Foliar application of kinetin (20 mg/L)
      is recommended at the first stage. A combination between soil and foliar
      application of 50% Hoagland solution is favorable to plant growth and
      developmental parameters including plant height, leaf width, stem base diameter,
      chlorophyll A and B, carotenoids, and indoles. The optimum values of vegetative
      growth parameters during the adaptation stage in a shaded nursery are achieved
      using planting medium containing peat moss/perlite 2:1 (v/v), while in a sunlight
      nursery, clay/perlite/compost at equal ratio is the best. This protocol is
      suitable for large-scale production of micropropagated date palm plantlets.

PMID- 28755347
TI  - Plant Regeneration from Somatic Embryogenic Suspension Cultures of Date Palm.
AB  - Somatic embryogenesis is one of the most important technologies for plant
      regeneration of elite date palm cultivars. Recently, considerable progress has
      been made in the development and optimization of this technique from embryogenic
      cell suspension cultures. This chapter describes a procedure for the rapid
      development of a large number of somatic embryos from embryogenic cell suspension
      cultures. An efficient plant regeneration protocol via somatic embryogenesis from
      cell suspension cultures starting with shoot-tip explants to plantlet
      acclimatization also is fully described. Low concentrations of 6
      benzylaminopurine (BAP) to 0.3 mg/L and high rate of subcultures each 7 days lead
      to improve the establishment and multiplication of somatic embryos in suspension
      cultures by limiting oxidative browning, associated with high total phenols and
      peroxidase activities. The detailed morphological observations have revealed the
      cells destined to become somatic embryos. Activated charcoal (AC) at 0.15 g/L has
      a positive effect on growth rate of somatic embryos by reducing tissue and medium
      browning, phenolics, and peroxidase activity.

PMID- 28755348
TI  - Synchronization of Somatic Embryogenesis in Date Palm Suspension Culture Using
      Abscisic Acid.
AB  - Somatic embryogenesis is considered the most effective method for commercial
      propagation of date palm. However, the limitation of obtaining synchronized
      development of somatic embryos remains an impediment. The synchronization of
      somatic embryo development is ideal for the applications to produce artificial
      seeds. Abscisic acid (ABA) is associated with stress response and influences in
      vitro growth and development. This chapter describes an effective method to
      achieve synchronized development of somatic embryos in date palm cell suspension
      culture. Among the ABA concentrations tested (0, 1, 10, 50, 100 MUM), the best
      synchronized growth was obtained in response to 50-100 MUM. Here we provide a
      comprehensive protocol for in vitro plant regeneration of date palm starting with
      shoot-tip explant, callus initiation and growth, cell suspension establishment,
      embryogenesis synchronization with ABA treatment, somatic embryo germination, and
      rooting as well as acclimatized plantlet establishment.

PMID- 28755349
TI  - Microcalli Induction in Protoplasts Isolated from Embryogenic Callus of Date
      Palm.
AB  - Date palm (Phoenix dactylifera L.) production is severely hampered due to several
      pests and diseases. Biotechnological tools such as protoplast fusion appear as an
      alternative to ensure rapid genetic improvement and multiplication of this
      species. However, establishment of an effective system of plant regeneration from
      protoplasts culture is a prerequisite for date palm somatic hybridization. In
      this chapter, we describe an effective protocol to induce microcalli in
      protoplasts isolated from nodular callus of important Algerian date palm
      cultivars. In this protocol, the main factors influencing the isolation (i.e.,
      enzymatic solution, mannitol concentration, duration, and mode of maceration) of
      protoplasts from the calli of Algerian date palm cultivars were optimized.
      Purified protoplasts were cultured on a semisolid medium supplemented with a
      hormonal balance of auxin and cytokinin to obtain microcalli formation.

PMID- 28755350
TI  - Temporary Immersion System for Date Palm Micropropagation.
AB  - The temporary immersion system (TIS) is being used with tremendous success for
      automation of micropropagation of many plant species. TIS usually consists of a
      culture vessel comprising two compartments, an upper one with the plant material
      and a lower one with the liquid culture medium and an automated air pump. The
      latter enables contact between all parts of the explants and the liquid medium by
      setting overpressure to the lower part of the container. These systems are
      providing the most satisfactory conditions for date palm regeneration via shoot
      organogenesis and allow a significant increase of multiplication rate (5.5-fold
      in comparison with that regenerated on agar-solidified medium) and plant material
      quality, thereby reducing production cost.

PMID- 28755351
TI  - Plantform Bioreactor for Mass Micropropagation of Date Palm.
AB  - A novel protocol for the commercial production of date palm through
      micropropagation is presented. This protocol includes the use of a semisolid
      medium alternation or in combination with a temporary immersion system (TIS,
      Plantform bioreactor) in date palm micropropagation. The use of the Plantform
      bioreactor for date palm results in an improved multiplication rate, reduced
      micropropagation time, and improved weaning success. It also reduces the cost of
      saleable units and thus improves economic return for commercial micropropagation.
      The use of the Plantform bioreactor successfully addresses other hindrances that
      can occur during the scale-up of date palm micropropagation, including asynchrony
      of somatic embryos, limited maturation of somatic embryos, and highly variable
      germination frequencies of embryos.

PMID- 28755352
TI  - Genetic Transformation of Date Palm Via Microprojectile Bombardment.
AB  - Efficient protocols for date palm embryogenic callus and somatic embryo
      transformation with uidA gene are described in this chapter. The embryogenic
      callus transformation procedure is 1.6 MUm gold particle size coated with 2.5 MUg
      DNA (pAct1-D plasmid), 1100 psi helium pressure, 9 cm target distance, 26 inHg
      vacuum pressure, 3 mm distance between the rupture disk and macrocarrier, and
      osmotic pretreatment with 0.4 M mannitol followed by 60 min air desiccation. The
      somatic embryo transformation procedure is 0.6 MUm gold particle size coated with
      2.5 MUg DNA (pAct1-D plasmid), 1350 psi helium pressure, 6 cm target distance, 28
      inHg vacuum pressure, 3 mm distance between the rupture disk and macrocarrier,
      and osmotic pretreatment with 0.4 M mannitol followed by 60 min air desiccation.
      Protocols for analysis of the transgenic plantlets have also been described.

PMID- 28755353
TI  - Microprojectile Bombardment Transformation of Date Palm Using the Insecticidal
      Cholesterol Oxidase (ChoA) Gene.
AB  - The overall objective of this work is to optimize the transformation system for
      date palm as a first step toward production of date palm clones resistant to
      noxious pests. A construct harboring the cholesterol oxidase (ChoA) gene, which
      renders plant resistance against insect attack, is introduced into embryogenic
      date palm callus using the PDS-1000/He particle bombardment system. The process
      involves the establishment of embryogenic callus cultures as well as immature
      embryo-derived microcalli that are used as target tissues for shooting and
      optimization of transformation conditions. This chapter in addition explains
      molecular and histochemical assays conducted to confirm gene integration and
      expression.

PMID- 28755354
TI  - Transient GUS Gene Expression in Date Palm Fruit Using Agroinjection
      Transformation Technique.
AB  - Transient expression of foreign genes in plant tissue is a valuable tool for
      testing the efficacy of transformation methods. In this work, we present, for the
      first time, the utilization of agroinjection as an efficient transformation
      system for gene delivery in date palm fruit. The research utilized Agrobacterium
      tumefaciens strain LBA4404 harboring the binary vector pRI201-AN-GUS carrying the
      beta-glucuronidase (GUS) gene, under the control of a CaMV 35S and kanamycin
      (NPTII) as an antibiotic gene under the control of a NOS promoter. Based on
      histochemical assay of agroinjected fruit for the GUS gene expressions, this
      protocol has proved to be an efficient and reliable tool for transgene expression
      in date palm. PCR for plasmid DNA, extracted from the transformed Agrobacterium,
      demonstrated the generation of the expected amplicon, corresponding to the GUS
      gene using GUS primers.

PMID- 28755355
TI  - Bioreactor Steroid Production and Analysis of Date Palm Embryogenic Callus.
AB  - Several compounds and families of compounds of date palm secondary metabolites
      have been investigated. The analysis of date palm tissue has shown the abundance
      of secondary metabolites including phytosterols, e.g., steroids, an important
      group of pharmaceutical compounds. Biotechnology offers the opportunity to
      utilize cells, tissues, and organs grown in vitro and manipulated to obtain
      desired compounds. This chapter presents a protocol for the production,
      determination, and identification of steroids in date palm callus tissue. The
      addition of 0.01 mg/L pyruvic acid as a precursor to MS liquid culture medium
      enhances steroid production. In addition, the chapter describes the sterol
      analytical techniques based on gas-liquid chromatography and gas chromatography
      mass spectrometry.

PMID- 28755356
TI  - Extraction and Estimation of Secondary Metabolites from Date Palm Cell Suspension
      Cultures.
AB  - The health benefits of dates arise from their content of phytochemicals, known
      for having pharmacological properties, including flavonoids, carotenoids,
      phenolic acids, sterols, procyanidins, and anthocyanins. In vitro cell culture
      technology has become an attractive means for the production of biomass and
      bioactive compounds. This chapter describes step-by-step procedures for the
      induction and proliferation of callus from date palm offshoots on Murashige and
      Skoog (MS) medium supplemented with plant growth regulators. Subsequently cell
      suspension cultures are established for optimum biomass accumulation, based on
      the growth curve developed by packed cell volume as well as fresh and dry
      weights. The highest production of biomass occurs at the 11th week after
      culturing. Moreover, this chapter describes methodologies for the extraction and
      analysis of secondary metabolites of date palm cell suspension cultures using
      high-performance liquid chromatography (HPLC). The optimum level of catechin,
      caffeic acid, apigenin, and kaempferol from the cell suspension cultures
      establishes after the 11th and 12th weeks of culture. This protocol is useful for
      scale-up production of secondary metabolites from date palm cell suspension
      cultures.

PMID- 28755357
TI  - In Vitro Assessment of Abiotic Stress in Date Palm: Salinity and Drought.
AB  - Date palm is one of the major crops growing in regions where abiotic stress
      conditions are extreme. Abiotic stress affects plant growth, development,
      physiology, and biochemical processes. This chapter describes a protocol to
      evaluate the response of date palm cultures to abiotic stresses. Tolerance to
      salinity stress is assessed using calcium chloride (CaCl2), potassium chloride
      (KCl), and sodium chloride (NaCl) at 11.96, 12.06, and 9.45 g/L, respectively
      (equivalent to 0.8 MPa osmotic potential), with different exposure durations (1
      12 days). Polyethylene glycol (PEG 8000) is tested at 0-30% (w/v) to assess
      tolerance to drought stress. Techniques are described to define the effects of
      these stress agents on the growth of callus and cell suspension cultures, water
      content, proline accumulation, and Na+ and K+ content ratio, in addition to the
      technique used for determining the median lethal dose (LD50) for PEG (29.5%) and
      NaCl (11.54 g/L). This protocol will be useful for future studies of in vitro
      selection of tolerant cell lines.

PMID- 28755358
TI  - Social Functioning and Behaviour in Mucopolysaccharidosis IH [Hurlers Syndrome].
AB  - BACKGROUND: Mucopolysaccharidosis type IH (MPS-IH) [Hurlers Syndrome] is a
      developmental genetic disorder characterised by severe physical symptoms and
      cognitive decline. This study aimed to investigate the behavioural phenotype of
      MPS-IH treated by haematopoietic cell transplantation, focusing on social
      functioning and sleep. Parental stress was also measured. METHODS: Participants
      were 22 children with MPS-IH (mean age 9 years 1 month), of whom 10 were male
      (45%). Parents completed the Social Responsiveness Scale (SRS), Child Behaviour
      Checklist (CBCL), Children's Sleep Habit Questionnaire and Parent Stress Index,
      Short Form (PSI-SF). RESULTS: Twenty-three per cent of children with MPS-IH
      scored in the severe range of the SRS, suggesting significant difficulties in
      social functioning. Children with MPS-IH were more than 30 times more likely to
      receive scores in the severe range than typically developing children. Thirty-six
      per cent scored in the mild-to-moderate range, suggesting milder, but marked,
      difficulties in social interaction. Although children with MPS-IH did not show
      significantly higher rates of internalising, externalising or total behaviour
      problems than the normative sample, they received scores that were significantly
      higher on social, thought and attention problems and rule-breaking behaviour, and
      all the competence areas of the CBCL. Parents of children with MPS-IH did not
      score significantly higher on parental stress than parents in a normative sample.
      CONCLUSIONS: Parents of children with MPS-IH rate their children as having
      problems with social functioning and various areas of competence more frequently
      than previously thought, with implications for clinical support.

PMID- 28755359
TI  - Four Years' Experience in the Diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase
      Deficiency in Infants Detected in Three Spanish Newborn Screening Centers.
AB  - Identification of very long-chain acyl-CoA dehydrogenase deficiency is possible
      in the expanded newborn screening (NBS) due to the increase in
      tetradecenoylcarnitine (C14:1) and in the C14:1/C2, C14:1/C16, C14:1/C12:1 ratios
      detected in dried blood spots. Nevertheless, different confirmatory tests must be
      performed to confirm the final diagnosis. We have revised the NBS results and the
      results of the confirmatory tests (plasma acylcarnitine profiles, molecular
      findings, and lymphocytes VLCAD activity) for 36 cases detected in three Spanish
      NBS centers during 4 years, correlating these with the clinical outcome and
      treatment. Our aim was to distinguish unambiguously true cases from disease
      carriers in order to obtain useful diagnostic information for clinicians that can
      be applied in the follow-up of neonates identified by NBS.Increases in C14:1 and
      of the different ratios, the presence of two pathogenic mutations, and deficient
      enzyme activity in lymphocytes (<12% of the intra-assay control) identified 12
      true-positive cases. These cases were given nutritional therapy and all of them
      are asymptomatic, except one. Seventeen individuals were considered disease
      carriers based on the mild increase in plasma C14:1, in conjunction with the
      presence of only one mutation and/or intermediate residual activity (18-57%). In
      addition, seven cases were classified as false positives, with normal biochemical
      parameters and no mutations in the exonic region of ACADVL. All these carriers
      and the false positive cases remained asymptomatic. The combined evaluation of
      the acylcarnitine profiles, genetic results, and residual enzyme activities have
      proven useful to definitively classify individuals with suspected VLCAD
      deficiency into true-positive cases and carriers, and to decide which cases need
      treatment.

PMID- 28755360
TI  - Mitochondrial Encephalopathy and Transient 3-Methylglutaconic Aciduria in ECHS1
      Deficiency: Long-Term Follow-Up.
AB  - We report the major diagnostic challenge in a female patient with signs and
      symptoms suggestive of an early-onset mitochondrial encephalopathy. Motor and
      cognitive development was severely delayed and brain MRI showed signal
      abnormalities in the putamen and caudate nuclei. Metabolic abnormalities included
      3-methylglutaconic aciduria and elevated lactate levels in plasma and
      cerebrospinal fluid, but were transient. Whole exome sequencing at the age of 25
      years finally revealed compound heterozygous mutations c.[229G>C];[563C>T],
      p.[Glu77Gln];[Ala188Val] in the ECHS1 gene. Activity of short-chain enoyl-CoA
      hydratase, a mitochondrial enzyme encoded by the ECHS1 gene, was markedly
      decreased in lymphocytes. Retrospective urine analysis confirms that elevated
      levels of S-(2-carboxypropyl)cysteamine, S-(2-carboxypropyl)cysteine, and N
      acetyl-S-(2-carboxypropyl)cysteine can be a diagnostic clue in the disease
      spectrum of ECHS1 mutations.

PMID- 28755361
TI  - Recombinant Overexpression of Mammalian TSPO Isoforms 1 and 2.
AB  - TSPO is a 18 kDa membrane protein that exists in mammalian as two isoforms 1 and
      2. They are involved in different functions and are located in different
      membranes. TSPO1 is mainly located in outer mitochondrial membrane, whereas TSPO2
      is encountered in plasma membrane of red blood cells. Determination of their
      structures is a milestone to understand their function. Their natural abundance
      is not sufficient to get large amounts usually required for structural studies.
      We described heterologous overexpression in both bacterial and cell-free system
      and purification on immobilized-metal affinity chromatography (IMAC) of both
      proteins. Using the same vector, TSPO1 is mostly recovered in bacterial inclusion
      bodies whereas TSPO2 is found in both bacterial cytosol and inclusion bodies, but
      in low amounts. Cell-free expression was the best system to overexpress pure
      TSPO2.

PMID- 28755362
TI  - Functional Assembly of Soluble and Membrane Recombinant Proteins of Mammalian
      NADPH Oxidase Complex.
AB  - Activation of phagocyte cells from an innate immune system is associated with a
      massive consumption of molecular oxygen to generate highly reactive oxygen
      species (ROS) as microbial weapons. This is achieved by a multiprotein complex,
      the so-called NADPH oxidase. The activity of phagocyte NADPH oxidase relies on an
      assembly of more than five proteins, among them the membrane heterodimer named
      flavocytochrome b 558 (Cytb 558), constituted by the tight association of the
      gp91phox (also named Nox2)  and p22phox proteins. The Cytb 558 is the membrane
      catalytic core of the NADPH oxidase complex, through which the reducing
      equivalent provided by NADPH is transferred via the associated prosthetic groups
      (one flavin and two hemes) to reduce dioxygen into superoxide anion. The other
      major proteins (p47phox, p67phox, p40phox, Rac) requisite for the complex
      activity are cytosolic proteins. Thus, the NADPH oxidase functioning relies on a
      synergic multi-partner assembly that in vivo can be hardly studied at the
      molecular level due to the cell complexity. Thus, a cell-free assay method has
      been developed to study the NADPH oxidase activity that allows measuring and
      eventually quantifying the ROS generation based on optical techniques following
      reduction of cytochrome c. This setup is a valuable tool for the identification
      of protein interactions, of crucial components and additives for a functional
      enzyme. Recently, this method was improved by the engineering and the production
      of a complete recombinant NADPH oxidase complex using the combination of purified
      proteins expressed in bacterial and yeast host cells. The reconstitution into
      artificial membrane leads to a fully controllable system that permits fine
      functional studies.

PMID- 28755363
TI  - Direct Extraction and Purification of Recombinant Membrane Proteins from Pichia
      pastoris Protoplasts.
AB  - In the past decade, the methylotrophic yeast Pichia pastoris has proved to be one
      of the most efficient systems for mass production of recombinant eukaryotic
      membrane proteins (MPs), leading to the crystallization and structure
      determination for a variety of them. The actual overexpression of functional MPs
      achieved with this system is, however, often accompanied by the formation of a
      variable but significant proportion of misfolded and/or aggregated proteins that
      are co-extracted and co-purified during the purification process. In order to
      minimize this unwanted phenomenon, we devised a novel procedure in which MPs
      produced in Pichia pastoris are directly solubilized from whole cells instead of
      crude membrane preparation. This approach aims at favoring the extraction of
      correctly folded membrane proteins that have been targeted to the plasma
      membrane, limiting the solubilization of the misfolded proteins and protein
      aggregates that are stored in internal membrane compartments. The method
      described herewith is based on the formation of protoplasts through enzymatic
      treatment prior to protein solubilization. This chapter details a set of
      protocols going from yeast cell preparation and protein solubilization to
      purification using affinity and size exclusion chromatography.

PMID- 28755364
TI  - Cell-Free Expression for the Study of Hydrophobic Proteins: The Example of Yeast
      ATP-Synthase Subunits.
AB  - Small hydrophobic membrane proteins or proteins with hydrophobic domains are
      often difficult to produce in bacteria. The cell-free expression system was found
      to be a very good alternative for the expression of small hydrophobic subunits of
      the yeast ATP-synthase, such as subunits e, g, k, i, f and the membrane domain of
      subunit 4, proteins that are suspected to play a role in the stability of ATP
      synthase dimers. All of these proteins could be produced in milligrams amounts
      using the cell-free "precipitate mode" and were successfully solubilized in the
      presence of lysolipid 1-myristoyl-2-hydroxy-sn-glycero-3-phospho-1'-rac-glycerol.
      Purified proteins were also found suitable for structural investigations. An
      example is given with the NMR backbone assignment of the isotopically labeled
      subunit g. Protocols are also described for raising specific polyclonal
      antibodies against overexpressed cell-free proteins.

PMID- 28755365
TI  - Wheat Germ Cell-Free Overexpression for the Production of Membrane Proteins.
AB  - Due to their hydrophobic nature, membrane proteins are notoriously difficult to
      express in classical cell-based protein expression systems. Often toxic, they
      also undergo degradation in cells or aggregate in inclusion bodies, making
      delicate issues further solubilization and renaturation. These are major
      bottlenecks in their structural and functional analysis. The wheat germ cell-free
      (WGE-CF) system offers an effective alternative not only to classical cell-based
      protein expression systems but also to other cell-free systems for the expression
      of membrane proteins. The WGE-CF indeed allows the production of milligram
      amounts of membrane proteins in a detergent-solubilized, homogenous, and active
      form. Here, we describe the method to produce a viral integral membrane protein,
      which is the non-structural protein 2 (NS2) of hepatitis C virus, in view of
      structural studies by solid-state NMR in a native-like lipid environment.

PMID- 28755366
TI  - Methyl-Specific Isotope Labeling Strategies for NMR Studies of Membrane Proteins.
AB  - Methyl groups are very useful probes of structure, dynamics, and interactions in
      protein NMR spectroscopy. In particular, methyl-directed experiments provide high
      sensitivity even in very large proteins, such as membrane proteins in a membrane
      mimicking environment. In this chapter, we discuss the approach for labeling
      methyl groups in E. coli-based protein expression, as exemplified with the
      mitochondrial carrier GGC.

PMID- 28755367
TI  - Labeling of Membrane Complexes for Electron Microscopy.
AB  - Localization of specific subunits or domains of interest inside protein complexes
      can be challenging, especially for membrane machineries. The amphipatic nature of
      their subunits and their modular organization results in difficult genetic
      manipulation and instability upon purification. Here, we present different
      labeling approaches that have been demonstrated successful in the structural
      characterization of large membrane complexes.

PMID- 28755368
TI  - Expression, Biochemistry, and Stabilization with Camel Antibodies of Membrane
      Proteins: Case Study of the Mouse 5-HT3 Receptor.
AB  - There is growing interest in the use of mammalian protein expression systems, and
      in the use of antibody-derived chaperones, for structural studies. Here, we
      describe protocols ranging from the production of recombinant membrane proteins
      in stable inducible cell lines to biophysical characterization of purified
      membrane proteins in complex with llama antibody domains. These protocols were
      used to solve the structure of the mouse 5-HT3 serotonin receptor but are of
      broad applicability for crystallization or cryo-electron microscopy projects.

PMID- 28755369
TI  - Characterization of New Detergents and Detergent Mimetics by Scattering
      Techniques for Membrane Protein Crystallization.
AB  - Membrane proteins are difficult to manipulate and stabilize once they have been
      removed from their native membranes. However, despite these difficulties,
      successes in membrane-protein structure determination have continued to
      accumulate for over two decades, thanks to advances in chemistry and technology.
      Many of these advances have resulted from efforts focused on protein engineering,
      high-throughput expression, and development of detergent screens, all with the
      aim of enhancing protein stability for biochemistry and biophysical studies. In
      contrast, considerably less work has been done to decipher the basic mechanisms
      that underlie the structure of protein-detergent complexes and to describe the
      influence of detergent structure on stabilization and crystallization. These
      questions can be addressed using scattering techniques (employing light, X-rays,
      and/or neutrons), which are suitable to describe the structure and conformation
      of macromolecules in solution, as well as to assess weak interactions between
      particles, both of which are clearly germane to crystallization. These techniques
      can be used either in batch modes or coupled to size-exclusion chromatography,
      and offer the potential to describe the conformation of a detergent-solubilized
      membrane protein and to quantify and model detergent bound to the protein in
      order to optimize crystal packing. We will describe relevant techniques and
      present examples of scattering experiments, which allow one to explore
      interactions between micelles and between membrane protein complexes, and relate
      these interactions to membrane protein crystallization.

PMID- 28755370
TI  - Secondary Structure Determination by Means of ATR-FTIR Spectroscopy.
AB  - Specialized infrared spectroscopic techniques have been developed that allow
      studying the secondary structure of membrane proteins and the influence of
      crucial parameters like lipid content and detergent. Here, we focus on an ATR
      FTIR spectroscopic study of Af-Amt1 and the influence of LDAO/glycerol on its
      structural integrity. Our results clearly indicate that infrared spectroscopy can
      be used to identify the adapted sample conditions.

PMID- 28755371
TI  - Native Mass Spectrometry for the Characterization of Structure and Interactions
      of Membrane Proteins.
AB  - Over the past years, native mass spectrometry and ion mobility have grown into
      techniques that are widely applicable to the study of aspects of protein
      structure. More recently, it has become apparent that this approach provides a
      very promising avenue for the investigation of integral membrane proteins in
      lipid or detergent environments.In this chapter, we discuss applications of
      native mass spectrometry and ion mobility in membrane protein research-what is
      important to take into consideration when working with membrane proteins, and
      what the requirements are for sample preparation for native mass spectrometry.
      Furthermore, we will discuss the types of information provided by the
      measurements, including the oligomeric state, subunit composition and
      stoichiometry, interactions with detergents or lipids, conformational
      transitions, and the binding and structural effect of ligands and drugs.

PMID- 28755372
TI  - Mass Spectrometry of Mitochondrial Membrane Protein Complexes.
AB  - The ATP production (oxidative phosphorylation) involves five complexes embedded
      in the inner membrane of mitochondria. The yeast Saccharomyces cerevisiae is
      mainly used as a model for the study of oxidative phosphorylation; mutants are
      easy to produce and are still viable due to their ability to grow using the
      fermentation pathway. Here, we present a process for analyzing mitochondrial
      respiratory complexes using native electrophoresis (BN-PAGE) coupled to LC-MS/MS.
      BN-PAGE (1) permits the separation of functional respiratory complexes, thus
      allowing in-gel activity detection of most of the respiratory complexes and (2)
      provides convenient samples for bottom-up proteomics. Combining BN-PAGE and LC
      MS/MS leads to the identification of the subunit composition of membrane
      complexes and offers the possibility of highlighting potential interacting
      proteins.

PMID- 28755373
TI  - Functional Studies on Membrane Proteins by Means of H/D Exchange in Infrared:
      Structural Changes in Na+ NQR from V. cholerae in the Presence of Lipids.
AB  - H/D exchange kinetics at the level of the amide proton in the mid infrared (1700
      1500 cm-1) make it possible to study the conformational flexibility of membrane
      proteins, independent of size or the presence of detergent or lipids. Slow,
      medium, and fast exchanging domains are distinguished, which reveal a different
      accessibility to the solvent. Whereas amide hydrogens undergo rapid exchange with
      solvent in an open structure, hydrogens experience much slower exchange when
      involved in H-bonded structures or when sterically inaccessible to the solvent.
      Here, we describe the protocol that was used to study the effect of phospholipids
      on the overall structure of the Na+ NQR from V. cholerae, a sodium pumping
      membrane protein.

PMID- 28755374
TI  - Reconstitution of Membrane Proteins in Liposomes.
AB  - Membrane protein reconstitution in liposomes is an invaluable technique to study
      numerous properties of membrane proteins in vitro. Kinetics, substrate
      specificity, and protein-protein interaction of membrane proteins can be
      investigated once they are embedded in the liposome bilayer. Both protocols
      described here aim to investigate the efflux pump MexA-MexB-OprM from Pseudomonas
      aeruginosa, a proteins complex embedded in both membranes of this Gram-negative
      bacteria. This tri-partite system, which by-passes the periplams, is involved in
      antibiotic resistance. First, we describe a protocol to study MexB, the actual
      transporter, and second we propose an alternate protocol where the tripartite
      system is investigated as a whole.

PMID- 28755375
TI  - Ion Channels as Reporters of Membrane Receptor Function: Automated Analysis in
      Xenopus Oocytes.
AB  - G-protein-coupled receptors (GPCR) are the most widely used system of
      communication used by cells. They sense external signals and translate them into
      intracellular signals. The information is carried mechanically across the cell
      membrane, without perturbing its integrity. Agonist binding on the extracellular
      side causes a change in receptor conformation which propagates to the
      intracellular side and causes release of activated G-proteins, the first
      messengers of a variety of signaling cascades.Permitting access to powerful
      electrophysiological techniques, ion channels can be employed to monitor
      precisely the most proximal steps of GPCR signaling, receptor conformational
      changes, and G-protein release. The former is achieved by physical attachment of
      a potassium channel to the GPCR to create an Ion-Channel Coupled Receptor (ICCR).
      The latter is based on the use of G-protein-regulated potassium channels (GIRK).
      We describe here how these two systems may be used in the Xenopus oocyte
      heterologous system with a robotic system for increased throughput.

PMID- 28755376
TI  - The CRACAM Robot: Two-Dimensional Crystallization of Membrane Protein.
AB  - Membrane proteins are key cellular components that perform essential functions.
      They are major therapeutic targets. Electron crystallography can provide
      structural experimental information at atomic scale for membrane proteins forming
      two-dimensional (2D) crystals. There are two different methods to produce 2D
      crystals of membrane proteins. (1) either directly in the bulk of the solution
      (2) or under a lipid monolayer at the air-water interface. This extra lipid
      monolayer helps to pre-orient the proteins in order to facilitate the growth of
      2D crystals. We present here these two methods for 2D crystallization of membrane
      proteins implemented in a fully automated robot called CRACAM. These methods
      require small volume of low concentration of proteins, making it possible to
      explore more conditions with the same amount of protein. These automated methods
      outperform traditional 2D crystallization approaches in terms of accuracy,
      flexibility, and throughput.

PMID- 28755377
TI  - Reconstitution of Membrane Proteins into Nanodiscs for Single-Particle Electron
      Microscopy.
AB  - The structure determination of integral membrane protein (IMP) in lipid
      environment is particularly challenging. Among emerging methods for exchanging
      detergent required for IMP purification by original compounds, the use of lipid
      nanodisc preserves a lipid environment. Compared with the classical method of
      proteoliposome formation, the nanodisc technology provides a better control of
      IMP molecules inserted in lipid membrane, therefore giving access to structural
      methodologies developed for soluble proteins. Here, we present the reconstitution
      of OprM membrane protein into nanodisc associated with a step of size-exclusion
      chromatography, an approach applicable to prepare IMPs for subsequent
      visualization by single-particle electron microscopy.

PMID- 28755378
TI  - Solid-State NMR of Membrane Protein Reconstituted in Proteoliposomes, the Case of
      TSPO.
AB  - Structural studies of membrane proteins (MP) in a native or native-like
      environment remain a challenge. X-ray crystallography of three-dimensional
      crystals of MP in lipids and cryo-electron microscopy of two-dimensional crystals
      also in lipids have given atomic structures of several MP. Recent developments of
      solid-state NMR (ssNMR) provided structural data of MP in lipids and should give
      access to the dynamic behavior of MP's in a native-like environment. Preparation
      of samples for ssNMR is not trivial with overexpressed proteins since purified
      recombinant MP have to be reincorporated in proteoliposomes and concentrated in
      the small volume of the rotor used for ssNMR studies. We present here the
      protocol that we have used to study the recombinant mouse TSPO1, an integral
      membrane protein of 20 kDa mostly found in the outer membrane of mitochondria and
      overexpressed in E. coli bacteria.

PMID- 28755379
TI  - Sample Preparation for Membrane Protein Structural Studies by Solid-State NMR.
AB  - Conformational studies of membrane proteins remain a challenge in the field of
      structural biology, and in particular the investigation of the proteins in a
      native-like lipid environment. Solid-state NMR presents a valuable opportunity
      for this, and we present here three critical steps in the solid-state NMR sample
      preparation, i.e., membrane reconstitution of the protein in native lipids, rotor
      filling, and sample quality assessment, at the example of the Bacillus subtilis
      ATP-binding cassette transporter BmrA.

PMID- 28755380
TI  - Simulation of Ligand Binding to Membrane Proteins.
AB  - Membrane proteins are involved in a large variety of functions. Most of these
      protein functions are regulated by ligand binding with diverse modes of action:
      agonists, partial agonists, antagonists, and allosteric modulators, potentiators
      and inhibitors. From the pharmacological point of view, membrane proteins are one
      if not the major target for drug development. However, experimental structure
      determination of membrane proteins in complex or in free form still represents a
      great challenge. Molecular dynamics (MD) simulations commonly reach the
      microsecond scale on membrane systems. This numerical tool is mature enough to
      predict and add molecular details on the different ligand-binding modes. In the
      present chapter, I will present the different steps to design, simulate, and
      analyze a MD simulation system containing a protein embedded in a membrane and
      surrounded by water and ligand. As an illustration, the simulation of the ligand
      gated ion channel gamma-aminobutyric acid type A receptor (GABAAR) surrounded by
      one of its allosteric potentiators, bromoform, will be presented and discussed.

PMID- 28755381
TI  - Molecular Modeling of Transporters: From Low Resolution Cryo-Electron Microscopy
      Map to Conformational Exploration. The Example of TSPO.
AB  - This chapter describes a protocol to establish a three-dimensional (3D) model of
      a protein and to explore its conformational landscape. It combines predictions
      from up-to-date bioinformatics methods with low-resolution experimental data. It
      also proposes to examine rapidly the dynamics of the protein using molecular
      dynamics simulations with a coarse-grained force field. Tools for analyzing these
      trajectories are suggested as well as those for constructing all-atoms models.
      Thus, starting from a protein sequence and using free software, the user can get
      important conformational information, which might improve the knowledge about the
      protein function.

PMID- 28755383
TI  - Solid bone tumors of the spine: Diagnostic performance of apparent diffusion
      coefficient measured using diffusion-weighted MRI using histology as a reference
      standard.
AB  - PURPOSE: To assess the diagnostic performance of mean apparent diffusion
      coefficient (mADC) in differentiating benign from malignant bone spine tumors,
      using histology as a reference standard. Conventional magnetic resonance imaging
      (MRI) sequences have good reliability in evaluating spinal bone tumors, although
      some features of benign and malignant cancers may overlap, making the
      differential diagnosis challenging. MATERIALS AND METHODS: In all, 116 patients
      (62 males, 54 females; mean age 59.5 +/- 14.1) with biopsy-proven spinal bone
      tumors were studied. Field strength/sequences: 1.5T MR system; T1 -weighted turbo
      spin-echo (repetition time / echo time [TR/TE], 500/13 msec; number of
      excitations [NEX], 2; slice thickness, 4 mm), T2 -weighted turbo spin-echo
      (TR/TE, 4100/102 msec; NEX, 2; slice thickness, 4 mm), short tau inversion
      recovery (TR/TE, 4800/89 msec; NEX, 2; slice thickness, 4 mm, IT, 140 msec),
      axial spin-echo echo-planar diffusion-weighted imaging (DWI) (TR/TE 5200/72 msec;
      slice thickness 5 mm; field of view, 300; interslice gap, 1.5 mm; NEX, 6; echo
      planar imaging factor, 96; no parallel imaging) with b-values of 0 and 1000
      s/mm2, and 3D fat-suppressed T1 -weighted gradient-recalled-echo (TR/TE, 500/13
      msec; slice thickness, 4 mm) after administration of 0.2 ml/kg body weight
      gadolinum-diethylenetriamine pentaacetic acid. Two readers manually drew regions
      of interest on the solid portion of the lesion (hyperintense on T2 -weighted
      images, hypointense on T1 -weighted images, and enhanced after gadolinium
      administration on fat-suppressed T1 -weighted images) to calculate mADC.
      Histology was used as the reference standard. Tumors were classified into
      malignant primary tumors (MPT), bone metastases (BM), or benign primary tumors
      (BPT). Statistical tests: Nonnormality of distribution was tested with the
      Shapiro-Wilk test. The Kruskal-Wallis and Mann-Whitney U-test with Bonferroni
      correction were used. Sensitivity and specificity of the mADC values for BM, MPT,
      and BPT were calculated. Approximate receiver operating characteristic curves
      were created. Interobserver reproducibility was evaluated using the intraclass
      correlation coefficient (ICC). RESULTS: The mADC values of MPT (n = 35), BM (n =
      65), and BPT (n = 16) were 1.00 +/- 0.32 (0.59-2.10) * 10-3 mm2 /s, 1.02 +/- 0.25
      (0.73-1.96) * 10-3 mm2 /s, 1.31 +/- 0.36 (0.83-2.14) * 10-3 mm2 /s, respectively.
      The mADC was significantly different between BPT and all malignant lesions
      (BM+MPT) (P < 0.001), BM and BPT (P = 0.008), and MPT and BPT (P = 0.008). No
      difference was found between BM and MPT (P = 0.999). An mADC threshold of 0.952 *
      10-3 mm2 /s yielded 81.3% sensitivity, 55.0% specificity. Accuracy was 76% (95%
      confidence interval [CI] = 63.9%-88.1%). Interobserver reproducibility was almost
      perfect (ICC = 0.916; 95% CI = 0.879-0.942). CONCLUSION: DWI with mADC
      quantification is a reproducible tool to differentiate benign from malignant
      solid tumors with 76% accuracy. The mADC values of BPT were statistically higher
      than that of malignant tumors. However, the large overlap between cases may make
      mADC not helpful in a specific patient. LEVEL OF EVIDENCE: 3 Technical Efficacy:
      Stage 2 J. Magn. Reson. Imaging 2018;47:1034-1042.

PMID- 28755382
TI  - Tools to define the melanoma-associated immunopeptidome.
AB  - Immunotherapies have been traditionally applied in malignant melanoma, which
      represent one of the most immunogenic tumours. Recently, immune checkpoint
      modulation has shown high therapeutic efficacy and may provide long-term survival
      in a significant proportion of affected patients. T cells are the major players
      in tumour rejection and recognize tumour cells predominantly in an MHC-dependent
      way. The immunopeptidome comprises the peptide repertoire presented by MHC class
      I and II molecules on the surface of the body's cells including tumour cells. To
      understand characteristics of suitable rejection antigens as well as respective
      effective T-cell responses, determination of the immunopeptidome is of utmost
      importance. Suitable rejection antigens need to be further characterized and
      validated not only to systematically improve current therapeutic approaches, but
      also to develop individualized treatment options. In this review, we report on
      current tools to explore the immunopeptidome in human melanoma and discuss
      current understanding and future developments to specifically detect and select
      those antigens that may be most relevant and promising for effective tumour
      rejection.

PMID- 28755384
TI  - Biosorption-based dispersive liquid-liquid microextraction combined with
      polypyrrole-coated magnetic nanoparticles as an effective sorbent for the
      extraction of ibuprofen from water samples using magnetic solid-phase extraction.
AB  - In this paper, biosorption-based dispersive liquid-liquid microextraction
      (BioDLLME) in combination with magnetic solid-phase extraction (MSPE) has been
      developed as a sample pretreatment method with high enrichment factor for the
      sensitive determination of ibuprofen in water samples. At first, magnetic Fe3 O4
      /polypyrrole nanoparticles were synthesized and employed as sorbent for the MSPE
      of ibuprofen. After the elution of the desired compound from the sorbent by using
      methanol, BioDLLME technique was performed on the obtained solution. After MSPE,
      the eluent of MSPE was used as the disperser solvent for BioDLLME, so that the
      extra preconcentration factor could be achieved. The properties of the prepared
      magnetic sorbent were characterized using field emission scanning electron
      microscopy, Fourier transform infrared spectroscopy and X-ray diffraction
      methods. Experimental parameters affecting the extraction efficiency were studied
      and optimized. Under optimum conditions, the enrichment factor was 274. The
      linear dynamic range and limit of detection are 0.25-80 and 0.083 MUg/L,
      respectively. The relative standard deviations for six replicate measurements are
      3.82%.

PMID- 28755385
TI  - Building and validating a prediction model for paediatric type 1 diabetes risk
      using next generation targeted sequencing of class II HLA genes.
AB  - AIM: It is of interest to predict possible lifetime risk of type 1 diabetes (T1D)
      in young children for recruiting high-risk subjects into longitudinal studies of
      effective prevention strategies. METHODS: Utilizing a case-control study in
      Sweden, we applied a recently developed next generation targeted sequencing
      technology to genotype class II genes and applied an object-oriented regression
      to build and validate a prediction model for T1D. RESULTS: In the training set,
      estimated risk scores were significantly different between patients and controls
      (P = 8.12 * 10-92 ), and the area under the curve (AUC) from the receiver
      operating characteristic (ROC) analysis was 0.917. Using the validation data set,
      we validated the result with AUC of 0.886. Combining both training and validation
      data resulted in a predictive model with AUC of 0.903. Further, we performed a
      "biological validation" by correlating risk scores with 6 islet autoantibodies,
      and found that the risk score was significantly correlated with IA-2A (Z-score =
      3.628, P < 0.001). When applying this prediction model to the Swedish population,
      where the lifetime T1D risk ranges from 0.5% to 2%, we anticipate identifying
      approximately 20 000 high-risk subjects after testing all newborns, and this
      calculation would identify approximately 80% of all patients expected to develop
      T1D in their lifetime. CONCLUSION: Through both empirical and biological
      validation, we have established a prediction model for estimating lifetime T1D
      risk, using class II HLA. This prediction model should prove useful for future
      investigations to identify high-risk subjects for prevention research in high
      risk populations.

PMID- 28755386
TI  - Variable silicon accumulation in plants affects terrestrial carbon cycling by
      controlling lignin synthesis.
AB  - Current climate and land-use changes affect regional and global cycles of silicon
      (Si), with yet uncertain consequences for ecosystems. The key role of Si in
      marine ecology by controlling algae growth is well recognized but research on
      terrestrial ecosystems neglected Si since not considered an essential plant
      nutrient. However, grasses and various other plants accumulate large amounts of
      Si, and recently it has been hypothesized that incorporation of Si as a
      structural plant component may substitute for the energetically more expensive
      biosynthesis of lignin. Herein, we provide evidence supporting this hypothesis.
      We demonstrate that in straw of rice (Oryza sativa) deriving from a large
      geographic gradient across South-East Asia, the Si concentrations (ranging from
      1.6% to 10.7%) are negatively related to the concentrations of carbon (31.3% to
      42.5%) and lignin-derived phenols (32 to 102 mg/g carbon). Less lignin may
      explain results of previous studies that Si-rich straw decomposes faster. Hence,
      Si seems a significant but hardly recognized factor in organic carbon cycling
      through grasslands and other ecosystems dominated by Si-accumulating plants.

PMID- 28755388
TI  - Killer-cell immunoglobulin-like receptors on the cusp of modern immunogenetics.
AB  - Killer-cell immunoglobulin-like receptors (KIR) and their human leukocyte antigen
      (HLA) ligands play a central role in immunity and human health. These molecules
      are encoded by gene families with copy number variation, extreme levels of
      sequence diversity and complex expression patterns. The rapid evolution of KIR
      and HLA genes and their associations with infectious diseases, pregnancy
      disorders, immunopathologies and outcome of cell transplantation have generated
      considerable interest from immunologists, geneticists and clinicians. Until
      recently, however, analyses have been stuck at low-level resolution, focusing
      primarily on presence or absence of KIR genes. This is changing with the advent
      of modern high throughput sequencing, cell phenotyping and bioinformatics. These
      developments allow high-resolution analysis and much deeper understanding of KIR
      evolution and KIR function. The impending deluge of high dimensional data brings
      inevitably new challenges in analysis, interpretation and communication of
      results, but the benefits are already tangible. The diversity of KIR across
      worldwide human populations is being catalogued at the allele level. Structures
      of KIR molecules and their interactions with HLA-peptide complexes are being
      determined. How KIR modulate natural killer cell education is being defined.
      Ligands for activating KIR, elusive for many years, are being discovered. KIR
      gene complexes and their related receptor gene families are being characterized
      in animal models and livestock breeds. These advances are helping to generate a
      more complete picture of the impact of KIR variation in health and disease and
      offer new opportunities for immunotherapy, as highlighted in a recent meeting
      (The Tenth KIR Workshop, April 2017 Cambridge, UK).

PMID- 28755387
TI  - BDNF genotype is associated with hippocampal volume in mild traumatic brain
      injury.
AB  - The negative long-term effects of mild traumatic brain injury (mTBI) have been a
      growing concern in recent years, with accumulating evidence suggesting that mTBI
      combined with additional vulnerability factors may induce neurodegenerative-type
      changes in the brain. However, the factors instantiating risk for
      neurodegenerative disease following mTBI are unknown. This study examined the
      link between mTBI and brain-derived neurotrophic factor (BDNF) genotype, which
      has previously been shown to regulate processes involved in neurodegeneration
      including synaptic plasticity and facilitation of neural survival through its
      expression. Specifically, we examined nine BDNF single-nucleotide polymorphisms
      (SNPs; rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850,
      rs11030107, rs7127507 and rs12273363) previously associated with brain atrophy or
      memory deficits in mTBI. Participants were 165 white, non-Hispanic Iraq and
      Afghanistan war veterans between the ages of 19 and 58, 110 of whom had at least
      one mTBI in their lifetime. Results showed that the BDNF SNP rs1157659 interacted
      with mTBI to predict hippocampal volume. Furthermore, exploratory analysis of
      functional resting state data showed that rs1157659 minor allele homozygotes with
      a history of mTBI had reduced functional connectivity in the default mode network
      compared to major allele homozygotes and heterozygotes. Apolipoprotein E (APOE)
      was not a significant predictor of hippocampal volume or functional connectivity.
      These results suggest that rs1157659 minor allele homozygotes may be at greater
      risk for neurodegeneration after exposure to mTBI and provide further evidence
      for a potential role for BDNF in regulating neural processes following mTBI.

PMID- 28755389
TI  - No calcitonin change in a person taking dulaglutide diagnosed with pre-existing
      medullary thyroid cancer.
AB  - BACKGROUND: Glucagon-like peptide-1 receptor agonists, such as dulaglutide,
      exenatide and liraglutide, are approved to treat Type 2 diabetes mellitus.
      Although these drugs provide substantial glycaemic control, studies in rodents
      have prompted concerns about the development of medullary thyroid carcinoma.
      These data are reflected in the US package insert, with boxed warnings and
      product labelling noting the occurrence of these tumours after clinically
      relevant exposures in rodents, and contraindicating glucagon-like peptide-1
      receptor agonist use in people with a personal or family history of medullary
      thyroid carcinoma, or in people with multiple endocrine neoplasia type 2.
      However, there are substantial differences between rodent and human responses to
      glucagon-like peptide-1 receptor agonists. This report presents the case of a
      woman with pre-existing medullary thyroid carcinoma who exhibited no significant
      changes in serum calcitonin levels despite treatment with dulaglutide 2.0 mg for
      6 months in the Assessment of Weekly AdministRation of LY2189265 [dulaglutide] in
      Diabetes-5 clinical study (NCT00734474). CASE REPORT: Elevated serum calcitonin
      was noted in a 56-year-old woman with Type 2 diabetes mellitus at the 6-month
      discontinuation visit in a study of long-term dulaglutide therapy. Retroactive
      assessment of serum collected before study treatment yielded an elevated
      calcitonin level. At 3 months post-study, calcitonin level remained elevated;
      ultrasonography revealed multiple bilateral thyroid nodules. Eventually,
      medullary thyroid carcinoma was diagnosed; the woman was heterozygous positive
      for a germline RET proto-oncogene mutation. CONCLUSION: The tumour was not
      considered stimulated by dulaglutide therapy because calcitonin remained stable
      throughout.

PMID- 28755390
TI  - Gentamicin, a read-through agent for the treatment of rectal cancer.

PMID- 28755391
TI  - Impact of winter roads on boreal peatland carbon exchange.
AB  - Across Canada's boreal forest, linear disturbances, including cutlines such as
      seismic lines and roads, crisscross the landscape to facilitate resource
      exploration and extraction; many of these linear disturbances cross peatland
      ecosystems. Changes in tree canopy cover and the compression of the peat by heavy
      equipment alter local thermal, hydrological, and ecological conditions, likely
      changing carbon exchange on the disturbance, and possibly in the adjacent
      peatland. We measured bulk density, water table, soil temperature, plant cover,
      and CO2 and CH4 flux along triplicate transects crossing a winter road through a
      wooded fen near Peace River, Alberta, Canada. Sample plots were located 1, 5, and
      10 m from the road on both sides with an additional three plots on the road.
      Productivity of the overstory trees, when present, was also determined. The
      winter road had higher bulk density, shallower water table, higher graminoid
      cover, and thawed earlier than the adjacent peatland. Tree productivity and CO2
      flux varied between the plots, and there was no clear pattern in relation to
      distance from the road. The plots on the winter road acted as a greater CO2 sink
      and greater CH4 source compared to the adjacent peatland with plots on the winter
      road emitting on average (standard error) 479 (138) compared to 41 (10) mg CH4  m
      2  day-1 in the adjacent peatland. Considering both gases, global warming
      potential increased from 70 to 250 g CO2 e m-2  year-1 in the undisturbed area to
      2100 g CO2 e m-2  year-1 on the winter road. Although carbon fluxes on any given
      cutline through peatland will vary depending on level of compaction, line width
      and vegetation community shifts, the large number of linear disturbances in
      Canada's boreal forest and slow recovery on peatland ecosites suggest they could
      represent an important anthropogenic greenhouse gas source.

PMID- 28755392
TI  - High expression of long non-coding HOX antisense transcript RNA and its clinical
      significance in cancer tissues: A meta-analysis.
AB  - BACKGROUND: HOX antisense transcript RNA (HOTAIR) is a 2148 nt long, intergenic,
      non-coding RNA molecule, which is reported to be highly expressed in many types
      of cancers. This meta-analysis summarizes its expression in cancer. METHODS: We
      searched all eligible papers on the prognostic impact of HOTAIR in cancer from
      inception to 30 September 2015 in PubMed, CBMdisc, and the CNKI database. Only
      full texts were included. Revman 5.3 was used for meta-analysis. RESULTS: A total
      of 11 studies of 1010 cases were included in the meta-analysis. HOTAIR expression
      was higher in: cancer tissues in than adjacent or normal tissues (odds ratio [OR]
      37.52, 95% confidence interval [CI] 18.94-74.31; P  < 0.00001); in cancer tissues
      with lymph node metastasis than in those without lymph node metastasis (OR 3.37,
      95% CI 2.36-4.82; P  < 0.00001); and in histological grades II-III than in
      histological gradeI(OR 0.47, 95% CI 0.29-0.75; P  = 0.002). CONCLUSION: This
      study shows that HOTAIR may play an important role in cancer occurrence and
      development, but whether it is a marker of cancer diagnosis and reliable
      prognosis remains to be confirmed. More rigorous design and meticulous quality
      epidemiological studies are required.

PMID- 28755393
TI  - Results of an Integrative Analysis: A Call for Contextualizing HIV and AIDS
      Clinical Practice Guidelines to Support Evidence-Based Practice.
AB  - BACKGROUND: Practice guidelines aim to improve the standard of care for people
      living with HIV/AIDS. Successfully implementing guidelines requires tailoring
      them to populations served and to social and organizational influences on care.
      AIMS: To examine dimensions of context, which nurses and midwives described as
      having a significant impact on their care of patients living with HIV/AIDS in
      Kenya, Uganda, South Africa, and Jamaica and to determine whether HIV/AIDS
      guidelines include adaptations congruent with these dimensions of context.
      METHODS: Two sets of data were used. The first came from a qualitative study. In
      depth interviews were conducted with purposively selected nurses, midwives, and
      nurse managers from 21 districts in four study countries. A coding framework was
      iteratively developed and themes inductively identified. Context dimensions were
      derived from these themes. A second data set of published guidelines for HIV/AIDS
      care was then assembled. Guidelines were identified through Google and PubMed
      searches. Using a deductive integrative analysis approach, text related to
      context dimensions was extracted from guidelines and categorized into problem and
      strategy statements. RESULTS: Ninety-six individuals participated in qualitative
      interviews. Four discrete dimensions of context were identified: health workforce
      adequacy, workplace exposure risk, workplace consequences for nurses living with
      HIV/AIDS, and the intersection of work and family life. Guidelines most often
      acknowledged health human resource constraints and presented mitigation
      strategies to offset them, and least often discussed workplace consequences and
      the intersections of family and work life. LINKING EVIDENCE TO ACTION: Guidelines
      should more consistently acknowledge diverse implementation contexts, propose how
      recommendations can be adapted to these realities, and suggest what role
      frontline healthcare providers have in realizing the structural changes necessary
      for healthier work environments and better patient care. Guideline
      recommendations should include more explicit advice on adapting their
      recommendations to different care conditions.

PMID- 28755394
TI  - Clinical similarity of the biosimilar ABP 501 compared with adalimumab after
      single transition: long-term results from a randomized controlled, double-blind,
      52-week, phase III trial in patients with moderate-to-severe plaque psoriasis.
AB  - BACKGROUND: ABP 501, a U.S.A. Food and Drug Administration- and European
      Medicines Agency-approved biosimilar, is highly similar to adalimumab in
      structure, function and pharmacokinetics. OBJECTIVES: To demonstrate similarity
      in efficacy, safety and immunogenicity of ABP 501 vs. adalimumab for moderate-to
      severe plaque psoriasis (clinical trial: NCT01970488). METHODS: Patients were
      randomized (1 : 1) to receive ABP 501 or adalimumab 40 mg every 2 weeks for 16
      weeks. At week 16, patients with >= 50% improvement from baseline in Psoriasis
      Area and Severity Index (PASI) score were eligible to continue to week 52.
      Patients receiving ABP 501 continued; adalimumab patients were rerandomized (1 :
      1) to continue adalimumab or undergo a single transition to ABP 501. Key efficacy
      assessments included percentage PASI improvement from baseline, PASI responders
      and mean change in affected body surface area from baseline to weeks 16, 32 and
      50. Safety was monitored via adverse events (AEs) and antidrug antibodies (ADAs)
      were assessed. RESULTS: A total of 308 patients were rerandomized at week 16 (ABP
      501/ABP 501, n = 152; adalimumab/adalimumab, n = 79; adalimumab/ABP 501, n = 77).
      PASI percentage improvements from baseline were similar across groups for weeks
      16, 32 and 50 (range: 85.8-88.2%), with no significant differences detected
      across groups in percentages of PASI 50, 75, 90 and 100 responders. Changes from
      baseline in percentage body surface area affected were similar across groups and
      time points. No new safety signals were detected. AEs were balanced between
      groups. Percentages of patients with binding and neutralizing ADAs were similar
      across treatments. CONCLUSIONS: ABP 501 and adalimumab have similar clinical
      efficacy, safety and immunogenicity profiles over 52 weeks, including after
      single transition, in this patient population.

PMID- 28755395
TI  - Enhancement of phytochemical content and drying efficiency of onions (Allium cepa
      L.) through blanching.
AB  - BACKGROUND: This study investigated the effect of blanching (60, 70 and 80 
      degrees C for 1, 3, 5 and 10 min) combined with oven drying at 60  degrees C on
      the phenolic compounds, antioxidant activity, colour and drying characteristics
      (drying time, drying rate constant, effective moisture diffusivity and activation
      energy) of onion slices. RESULTS: Blanching of onion slices at 60  degrees C for
      3 min and at 70  degrees C for 1 min prior to drying increased their bioactive
      compounds and antioxidant activity compared to the control samples and other
      treatments. Eighteen drying models were evaluated. The Modified Page and two-term
      exponential models best represented the drying data. The effective diffusivity
      ranged from 3.32 * 10-11 m2 s-1 (control) to 5.27 * 10-11 m2 s-1 , 5.01 * 10-11
      m2 s-1 , and 4.74 * 10-11 m2 s-1 for onions blanched at 60  degrees C, 70 
      degrees C and 80  degrees C, respectively. The higher activation energy was
      observed for the control (unblanched) sample and slightly lower values were found
      for 1 min- and 3 min-blanched samples, confirming the higher drying efficiency as
      a result of the blanching pre-treatment. CONCLUSION: The use of blanching as a
      pre-treatment before drying of onions resulted in enhanced phytochemical content
      and drying efficiency. (c) 2017 Society of Chemical Industry.

PMID- 28755396
TI  - Allometry and morphometrics of clypeal membrane size and shape in Nicrophorus
      (Coleoptera: Silphidae).
AB  - Contests between same-sex opponents over resources necessary for reproduction, as
      well interactions used to discern mate quality, often involve exaggerated traits
      wherein large individuals have disproportionately larger traits. This positive
      allometric scaling of weapons or signals facilitates communication during social
      interactions by accentuating body size differences between individuals.
      Typically, males carry these exaggerated traits, as males must compete over
      limited female gametes. However, in Nicrophorus beetles both males and females
      engage in physical contests over the vertebrate carcasses they need to provision
      and raise offspring. Male and female Nicrophorus beetles have extended clypeal
      membranes directly above their mandibles, which could serve as signals. We
      investigated the scaling relationships between clypeal membrane size and shape
      and body size for five species of North American burying beetle to determine
      whether clypeal membranes contain exaggerated body size information. We found
      that clypeal membranes for both sexes of all species scaled positively with body
      size (slope > 1). Three of the five species also displayed sexual dimorphism in
      aspects of clypeal membrane size and shape allometry despite lack of dimorphism
      in body size. In two dimorphic species, small male clypeal membranes were
      statistically indistinguishable from the female form. We conclude that colored
      clypeal membranes in Nicrophorus beetles do contain exaggerated body size
      information. Observed patterns of dimorphism suggest that males sometimes
      experience stronger selection on marking size and shape, which might be explained
      by life history differences among species.

PMID- 28755397
TI  - The Introduction and Clinical Use of Cardiac-Specific Troponin Assays.
AB  - The earliest biomarkers introduced to diagnose myocardial infarction (MI) such as
      aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) lacked cardiac
      specificity and were replaced by creatine kinase (CK), the CK-MB isoenzyme, and
      ultimately the cardiac-specific troponins (cTnT and cTnI). This has opened up the
      possibilities of ruling out MI more rapidly and also identifying patients with a
      chronic elevation of cTn and a poor prognosis in a range of cardiac conditions.

PMID- 28755398
TI  - Microfluidic Lithography of Bioinspired Helical Micromotors.
AB  - Considerable efforts have been devoted to developing artificial micro/nanomotors
      that can convert energy into movement. A flow lithography integrated microfluidic
      spinning and spiraling system is developed for the continuous generation of
      bioinspired helical micromotors. Because the generation processes could be
      precisely tuned by adjusting the flow rates and the illuminating frequency, the
      length, diameter, and pitch of the helical micromotors were highly controllable.
      Benefiting from the fast online gelation and polymerization, the resultant
      helical micromotors could be imparted with Janus, triplex, and core-shell cross
      sectional structures that have never been achieved by other methods. Owing to the
      spatially controlled encapsulation of functional nanoparticles in the
      microstructures, the helical micromotors can perform locomotion not only by
      magnetically actuated rotation or corkscrew motion but also through chemically
      powered catalytic reaction.

PMID- 28755399
TI  - Intraoperative image guidance in transoral robotic surgery: A pilot study.
AB  - BACKGROUND: Intraoperative image guidance during transoral robotic surgery (TORS)
      is hampered by imaging-friendly instrumentation and intraoperative positioning.
      The purpose of this study was to develop and validate an accurate image-guidance
      system for TORS. METHODS: A custom radiolucent mouth retractor was fabricated
      from biocompatible material (Med-610; Stratasys, Minneapolis, MN). Teflon beads
      were placed in the oropharynx and carotid arteries of 3 cadavers. CT scans were
      obtained in the preoperative and intraoperative positions. Displacement of
      targets between preoperative and intraoperative scans was measured. Surgical
      navigation was based on the open-source Image-Guided Surgery Toolkit. Target
      registration error (TRE) was determined by measuring the distance between the
      tracker and bead registered to preoperative versus intraoperative scans. RESULTS:
      The inferior oropharyngeal targets demonstrated the greatest displacement between
      positions. A significant reduction in TRE was observed when registering the
      tracker to the intraoperative compared to the preoperative scan. CONCLUSION: This
      study describes an accurate intraoperative image-guidance system for TORS.

PMID- 28755400
TI  - Mapping the in vitro interactome of cardiac sodium (Na+ )-calcium (Ca2+ )
      exchanger 1 (NCX1).
AB  - The sodium (Na+ )-calcium (Ca2+ ) exchanger 1 (NCX1) is an antiporter membrane
      protein encoded by the SLC8A1 gene. In the heart, it maintains cytosolic Ca2+
      homeostasis, serving as the primary mechanism for Ca2+ extrusion during
      relaxation. Dysregulation of NCX1 is observed in end-stage human heart failure.
      In this study, we used affinity purification coupled with MS in rat left
      ventricle lysates to identify novel NCX1 interacting proteins in the heart. Two
      screens were conducted using: (1) anti-NCX1 against endogenous NCX1 and (2) anti
      His (where His is histidine) with His-trigger factor-NCX1cyt recombinant protein
      as bait. The respective methods identified 112 and 350 protein partners, of which
      several were known NCX1 partners from the literature, and 29 occurred in both
      screens. Ten novel protein partners (DYRK1A, PPP2R2A, SNTB1, DMD, RABGGTA,
      DNAJB4, BAG3, PDE3A, POPDC2, STK39) were validated for binding to NCX1, and two
      partners (DYRK1A, SNTB1) increased NCX1 activity when expressed in HEK293 cells.
      A cardiac NCX1 protein-protein interaction map was constructed. The map was
      highly connected, containing distinct clusters of proteins with different
      biological functions, where "cell communication" and "signal transduction" formed
      the largest clusters. The NCX1 interactome was also significantly enriched with
      proteins/genes involved in "cardiovascular disease" which can be explored as
      novel drug targets in future research.

PMID- 28755401
TI  - Association between the scores of the Japanese version of the Brief Assessment of
      Cognition in Schizophrenia and whole-brain structure in patients with chronic
      schizophrenia: A voxel-based morphometry and diffusion tensor imaging study.
AB  - AIM: The Brief Assessment of Cognition in Schizophrenia (BACS) is a concise tool
      designed to evaluate cognitive deficits in schizophrenia. We examined the
      possible association between BACS scores and whole-brain structure, as observed
      using magnetic resonance imaging with a relatively large sample. METHODS: The
      study sample comprised 116 patients with schizophrenia (mean age, 39.3 +/- 11.1
      years; 66 men) and 118 healthy controls (HC; mean age, 40.0 +/- 13.6 years; 58
      men) who completed the Japanese version of the BACS (BACS-J). All participants
      were of Japanese ethnicity. The magnetic resonance imaging volume and diffusion
      tensor imaging data were processed with voxel-based morphometry and tract-based
      spatial statistics, respectively. RESULTS: There were significant reductions in
      the regional gray matter volumes and white matter fractional anisotropy values in
      patients with schizophrenia compared to HC. For the gray matter areas, the
      working memory score had a significant positive correlation with the anterior
      cingulate and medial frontal cortices volumes in the patients. For the white
      matter areas, the motor speed score had a significant positive correlation with
      fractional anisotropy values in the corpus callosum, internal capsule, superior
      corona radiata, and superior longitudinal fasciculus in the patients. However,
      there was no significant correlation among either the gray or white matter areas
      in the HC. CONCLUSION: Our results suggest that among the BACS-J measures, the
      working memory and motor speed scores are associated with several structural
      alterations in the brains of patients with schizophrenia.

PMID- 28755402
TI  - Combination of a 2940 nm Er:YAG laser with recombinant bovine basic fibroblast
      growth factor (rb-bFGF) and light-emitting diode-red light (LED-RL) for the
      treatment of striae alba: A pilot study.
AB  - BACKGROUND: Striae distensae (SD) are a common dermatologic problem that plagues
      many people. Although there are many therapeutic modalities have been used to
      treat SD, effective method has been disappointing for striae Alba. AIMS: To
      evaluate the clinical and histopathologic efficacy and safety of the 2940-nm
      erbium yttrium aluminum garnet (Er:YAG) ablative fractional laser (AFL) with
      recombinant bovine basic fibroblast growth factor (rb-bFGF) and light-emitting
      diode-red light (LED-RL) for the treatment of striae alba. PATIENTS AND METHODS:
      Thirty volunteers with striae distensae alba were enrolled. The subjects
      completed treatments with the 2940-nm Er:YAG AFL 6 times at 4-week intervals.
      Following this treatment, the subjects were required to spray rb-BFGF for 1 week
      at home. They then received LED-RL once every 7 days for three sessions between
      the two laser treatments. Two independent investigators evaluated clinical
      improvement at pretreatment and 1, 3, 6, and 12 months post-treatment, patients
      also provided self-assessments of clinical improvement. Two biopsies were
      obtained from two subjects, both of the same sites of striae alba, one before the
      first treatment and one 6 months after the last session. RESULTS: All 30 subjects
      demonstrated clinical improvement after treatment. Skin biopsies after treatment
      showed an increase in epidermal thickness, dermal thickness, and collagen and
      elastin density when compared to that at the baseline. CONCLUSIONS: The
      combination of the 2940-nm Er:YAG laser with rb-bFGF and LED-RL for the treatment
      of striae alba was a safe and effective approach for improving the appearance of
      striae alba.

PMID- 28755403
TI  - Monitoring deep inspiration breath hold for left-sided localized breast cancer
      radiotherapy with an in-house developed laser distance meter system.
AB  - Deep inspiration breath hold (DIBH) in left-sided breast cancer radiotherapy is a
      technique to reduce cardiac and pulmonary doses while maintaining target
      coverage. This study aims at evaluating an in-house developed DIBH system. Free
      breathing (FB) and DIBH plans were generated for 22 left-sided localized breast
      cancer patients who had radiation therapy (RT) after breast-conserving surgery.
      All patients were treated utilizing an in-house laser distance measuring system.
      50 Gy was prescribed, and parameters of interest were target coverage, left
      anterior descending coronary artery, (LAD) and heart doses. Portal images were
      acquired and the reproducibility and stability of DIBH treatment were compared to
      FB. The comparing result shows there is a significant reduction in all LAD and
      heart dose statistics for DIBH compared to FB plans without compromising the
      target coverage. The maximum LAD dose was reduced from 43.7 Gy to 29.0 Gy and the
      volume of the heart receiving >25 Gy was reduced from 3.3% to 1.0% using the in
      house system, both statistically significant. The in-house system gave a
      reproducible and stable DIBH treatment where the systematic error ?, and random
      error sigma, were less than 2.2 mm in all directions, but were not significantly
      better than at FB. The system was well tolerated and all patients completed their
      treatment sessions with DIBH.

PMID- 28755404
TI  - The dense-core vesicle maturation protein CCCP-1 binds RAB-2 and membranes
      through its C-terminal domain.
AB  - Dense-core vesicles (DCVs) are secretory organelles that store and release
      modulatory neurotransmitters from neurons and endocrine cells. Recently, the
      conserved coiled-coil protein CCCP-1 was identified as a component of the DCV
      biogenesis pathway in the nematode Caenorhabditis elegans. CCCP-1 binds the small
      GTPase RAB-2 and colocalizes with it at the trans-Golgi. Here, we report a
      structure-function analysis of CCCP-1 to identify domains of the protein
      important for its localization, binding to RAB-2, and function in DCV biogenesis.
      We find that the CCCP-1 C-terminal domain (CC3) has multiple activities. CC3 is
      necessary and sufficient for CCCP-1 localization and for binding to RAB-2, and is
      required for the function of CCCP-1 in DCV biogenesis. In addition, CCCP-1 binds
      membranes directly through its CC3 domain, indicating that CC3 may comprise a
      previously uncharacterized lipid-binding motif. We conclude that CCCP-1 is a
      coiled-coil protein that binds an activated Rab and localizes to the Golgi via
      its C-terminus, properties similar to members of the golgin family of proteins.
      CCCP-1 also shares biophysical features with golgins; it has an elongated shape
      and forms oligomers.

PMID- 28755405
TI  - Serum IFN-gamma Predicts the Therapeutic Effect of Mesenchymal Stem Cells
      Transplantation in Systemic Lupus Erythematosus Patients.
AB  - Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) show immunoregulatory
      properties on various immune cells and display therapeutic effects on various
      autoimmune diseases such as systemic lupus erythematosus (SLE). The aim of this
      study was to investigate the effect of the SLE environment on UC MSCs and to
      identify a potential serum biomarker to predict the therapeutic effect. UC MSCs
      were cocultured with peripheral blood mononuclear cells (PBMCs) from active lupus
      patients, and the proliferation, apoptosis and surface markers of UC MSCs were
      observed. UC MSC functional molecules were assessed by real-time polymerase chain
      reaction, and the signaling pathways were analyzed by Western blot. The clinical
      effect of MSC transplantation (MSCT) for lupus patients was followed-up, whereas
      baseline serum cytokines were analyzed by enzyme-linked immunosorbent assay. The
      coculture of PBMC from lupus patients promoted MSC proliferation. Lupus PBMCs
      were more potent in stimulating UC MSCs to secrete vascular endothelial growth
      factor (VEGF) and CXCL-12. Furthermore, lupus PBMCs activated Akt, IkappaB, and
      Stat5 signaling pathways in UC MSCs but did not affect Erk1/2 and Smad1/5/8
      pathways. Moreover, our clinical study showed that higher baseline levels of IFN
      gamma might predict a good response to MSCT in active lupus patients. Baseline
      IFN-gamma levels may predict clinical response to MSC therapy for active lupus
      patients, which will help to choose suitable patients for clinical
      transplantation. Stem Cells Translational Medicine 2017;6:1777-1785.

PMID- 28755406
TI  - Effect of apple polyphenols on vascular oxidative stress and endothelium
      function: a translational study.
AB  - SCOPE: We aimed examining apple polyphenols' effect on uricemia and endothelial
      function in a sample of overweight subjects. METHODS AND RESULTS: This was a two
      phased study. In vitro experiment aimed to evaluate apple polyphenols' ability to
      lower uric acid in comparison with allopurinol. In vivo study consisted in a
      randomized, double-blind, parallel placebo-controlled clinical trial involving 62
      overweight volunteers with suboptimal values of fasting plasma glucose (100
      mg/dL<=FPG<=125 mg/dL), randomized to 300 mg apple polyphenols or placebo for 8
      weeks. Apple polyphenols extract inhibited xanthine oxidase activity, with an
      IC50 = 130 +/- 30 ng/mL; reducing uric acid production with an IC50 = 154 +/- 28
      ng/mL. During the trial, after the first 4 weeks of treatment, FPG decreased in
      the active treated group (-6.1%, p < 0.05), while no significant changes were
      observed regarding the other hematochemistry parameters. After 4 more weeks of
      treatment, active-treated patients had an improvement in FPG compared to baseline
      (-10.3%, p < 0,001) and the placebo group (p < 0,001). Uric acid (-14.0%, p <
      0.05 versus baseline; p < 0.05 versus placebo) and endothelial reactivity (0.24+/
      0.09, p = 0.009 versus baseline; p < 0.05 versus placebo) significantly improved
      too. CONCLUSION: In vivo, apple polyphenols extract has a positive effect on
      vascular oxidative stress and endothelium function and reduce FPG and uric acid
      by inhibiting xanthine oxidase, as our In vitro experiment attests.

PMID- 28755407
TI  - The impact of modifying photosystem antenna size on canopy photosynthetic
      efficiency-Development of a new canopy photosynthesis model scaling from
      metabolism to canopy level processes.
AB  - Canopy photosynthesis (Ac ) describes photosynthesis of an entire crop field and
      the daily and seasonal integrals of Ac positively correlate with daily and
      seasonal biomass production. Much effort in crop breeding has focused on
      improving canopy architecture and hence light distribution inside the canopy.
      Here, we develop a new integrated canopy photosynthesis model including canopy
      architecture, a ray tracing algorithm, and C3 photosynthetic metabolism to
      explore the option of manipulating leaf chlorophyll concentration ([Chl]) for
      greater Ac and nitrogen use efficiency (NUE). Model simulation results show that
      (a) efficiency of photosystem II increased when [Chl] was decreased by decreasing
      antenna size and (b) the light received by leaves at the bottom layers increased
      when [Chl] throughout the canopy was decreased. Furthermore, the modelling
      revealed a modest ~3% increase in Ac and an ~14% in NUE was accompanied when
      [Chl] reduced by 60%. However, if the leaf nitrogen conserved by this decrease in
      leaf [Chl] were to be optimally allocated to other components of photosynthesis,
      both Ac and NUE can be increased by over 30%. Optimizing [Chl] coupled with
      strategic reinvestment of conserved nitrogen is shown to have the potential to
      support substantial increases in Ac , biomass production, and crop yields.

PMID- 28755408
TI  - Effects of simple rain-shelter cultivation on fatty acid and amino acid
      accumulation in 'Chardonnay' grape berries.
AB  - BACKGROUND: Fatty acids and amino acids are the precursors of aliphatic and
      aromatic volatile compounds, higher alcohols and esters. They are also nutrition
      for yeast metabolism during fermentation. However, few reports have been
      concerned about the effect of viticulture practices on the accumulation of fatty
      acids and amino acids in wine grapes. This study aimed to explore the
      accumulation of these compounds in developing Vitis vinifera L. cv. Chardonnay
      grape berries under two vintages, and compare the influences of the rain-shelter
      cultivation and open-field cultivation. RESULTS: Fifteen fatty acids and 21 amino
      acids were detected in total. The rain-shelter cultivation led to an increase in
      the total concentration of fatty acids, and a decrease in the total concentration
      of amino acids compared with the open-field cultivation in 2012, while no
      significant difference was observed between two cultivation modes in 2013
      vintage. Concentrations of palmitoleic acid, isoleucine and cysteine were
      significantly promoted in the rain-shelter grape berries, whereas those of
      tyrosine and ornithine were markedly reduced in both vintages. CONCLUSION: The
      rain-shelter cultivation of wine grapes in the rainy region is beneficial for
      improving grape quality and fermentation activity by influence on the
      concentration of fatty acids and amino acids. (c) 2017 Society of Chemical
      Industry.

PMID- 28755409
TI  - A first-in-human pharmacodynamic and pharmacokinetic study of a fully human anti
      glucagon receptor monoclonal antibody in normal healthy volunteers.
AB  - AIMS: Glucagon receptor (GCGR) blockers are being investigated as potential
      therapeutics for type 1 and type 2 diabetes. Here we report the safety,
      tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of REGN1193, a
      fully human glucagon receptor blocking monoclonal antibody from a first-in-human
      healthy volunteer randomized double-blinded trial. METHODS: Healthy men and women
      received single ascending doses of REGN1193 ranging from 0.05 to 0.6 mg/kg (n =
      42) or placebo (n = 14) intravenously. Safety, tolerability and PK were assessed
      over 106 days. The glucose-lowering effect of REGN1193 was assessed after
      induction of hyperglycaemia by serial glucagon challenges. RESULTS: REGN1193 was
      generally well tolerated. There were small (<3* the upper limit of normal) and
      transient dose-dependent increases in hepatic aminotransferases. No increase in
      LDL-C was observed. Hypoglycaemia, assessed as laboratory blood glucose <=70
      mg/dL, occurred in 6/14 (43%) subjects on placebo and 27/42 (57%) on REGN1193
      across all dose groups. All episodes of hypoglycaemia were asymptomatic, >50
      mg/dL, and did not require treatment or medical assistance. Concentration-time
      profiles suggest a 2-compartment disposition and marked nonlinearity, consistent
      with target-mediated clearance. REGN1193 inhibited the glucagon-stimulated
      glucose increase in a dose-dependent manner. The 0.6 mg/kg dose inhibited the
      glucagon-induced glucose area under the curve for 0 to 90 minutes (AUC0-90
      minutes ) by 80% to 90% on days 3 and 15, while blunting the increase in C
      peptide. REGN1193 dose-dependently increased total GLP-1, GLP-2 and glucagon,
      with plasma levels returning to baseline by day 29 in all dose groups.
      CONCLUSION: REGN1193, a GCGR-blocking monoclonal antibody, produced a safety,
      tolerability and PK/PD profile suitable for further clinical development. The
      occurrence of transient elevations in serum hepatic aminotransferases observed
      here and reported with several small molecule glucagon receptor antagonists
      suggests an on-target effect of glucagon receptor blockade. The underlying
      mechanism is unknown.

PMID- 28755410
TI  - Chemical Origin of the Stability Difference between Copper(I)- and Silver(I)
      Based Halide Double Perovskites.
AB  - Recently, CuI - and AgI -based halide double perovskites have been proposed as
      promising candidates for overcoming the toxicity and instability issues inherent
      within the emerging Pb-based halide perovskite absorbers. However, up to date,
      only AgI -based halide double perovskites have been experimentally synthesized;
      there are no reports on successful synthesis of CuI -based analogues. Here we
      show that, owing to the much higher energy level for the Cu 3d10 orbitals than
      for the Ag 4d10 orbitals, CuI atoms energetically favor 4-fold coordination,
      forming [CuX4 ] tetrahedra (X=halogen), but not 6-fold coordination as required
      for [CuX6 ] octahedra. In contrast, AgI atoms can have both 6- and 4-fold
      coordinations. Our density functional theory calculations reveal that the
      synthesis of CuI halide double perovskites may instead lead to non-perovskites
      containing [CuX4 ] tetrahedra, as confirmed by our material synthesis efforts.

PMID- 28755411
TI  - Associations of current diet with plasma and urine TMAO in the KarMeN study:
      direct and indirect contributions.
AB  - SCOPE: Knowledge on the influence of current diet on trimethylamine-N-oxide
      (TMAO) levels in humans is still inconsistent. Thus, we aimed to investigate
      associations of current diet with urine and plasma TMAO levels and to determine
      the effect of different foods on TMAO variation. METHODS AND RESULTS: TMAO
      concentrations of 297 healthy individuals were assessed using 1 H-NMR
      spectroscopy for 24 h urine collection and spot urine, and LC-MS for plasma. Of
      35 assessed food groups, those with a correlation of rho >|0.15| with plasma or
      urine TMAO levels were further investigated in multivariate linear regression
      models showing current fish and (red) meat consumption as plausible dietary
      sources of TMAO. Overall, explained variance of TMAO levels by current diet and
      co-variables (age, sex, lean body mass, glomerular filtration rate) was small.
      Associations with urine and plasma concentrations differed depending on the TMAO
      source. Fish consumption was associated with urine and plasma TMAO
      concentrations, whereas meat consumption was only associated with TMAO
      concentrations in plasma. Furthermore, associations of plasma TMAO concentration
      with fish consumption were two times stronger than with meat consumption.
      CONCLUSION: Meat and fish consumption differentially affects TMAO concentrations
      in body fluids. Only a small fraction of variance is explained by current diet.

PMID- 28755412
TI  - Mechanisms of Mendelian dominance.
AB  - Genetic dominance has long been considered as a qualitative reflection of
      interallelic interactions. Dominance arises from many multiple sources whose
      unifying theme is the existence of non-linear relationships between the genotypic
      and phenotypic values. One of the clearest examples are dominant negative
      mutations (DNMs) in which a defective subunit poisons a macromolecular complex.
      Dominance can also be due to the presence of a heterozygous null allele, as is
      the case of haploinsufficiency. Dominance can also be influenced by epistatic
      (interloci) interactions. For instance, a pre-existing genetic variant can make
      possible the expression of a pathogenic variant in a seemingly "dominant"
      fashion. Such interactions, which can make an individual more or less sensitive
      to a particular pathogenic variant, will also be discussed here.

PMID- 28755413
TI  - Response to "The Role of FcRn in the Pharmacokinetics of Biologics in Patients
      with Multiple Myeloma".

PMID- 28755414
TI  - Successful use of digoxin-specific immune Fab in the treatment of severe Nerium
      oleander toxicosis in a dog.
AB  - OBJECTIVE: To describe a case in which digoxin-specific immune Fab was used
      successfully in a dog with severe oleander toxicosis secondary to ingesting plant
      material. CASE SUMMARY: A 6-year-old intact female Rhodesian Ridgeback mixed
      breed dog was presented for severe oleander toxicosis and was refractory to all
      antiarrhythmic therapies and supportive care. Digoxin-specific immune Fab was
      successful in treating this dog. The dog recovered but suffered ischemic
      injuries, the long-term effects of which are unknown. NEW OR UNIQUE INFORMATION
      PROVIDED: This report describes the successful use of digoxin-specific immune Fab
      in the treatment of oleander toxicosis in a dog, which has not previously been
      published in veterinary literature. Oleander poisoning can be associated with
      permanent cardiac arrhythmias due to the ischemic damage.

PMID- 28755415
TI  - Accelerometer-Measured Moderate to Vigorous Physical Activity and Incidence Rates
      of Falls in Older Women.
AB  - OBJECTIVES: To examine whether moderate to vigorous physical activity (MVPA)
      measured using accelerometry is associated with incident falls and whether
      associations differ according to physical function or history of falls. DESIGN:
      Prospective study with baseline data collection from 2012 to 2014 and 1 year of
      follow-up. SETTING: Women's Health Initiative participants living in the United
      States. PARTICIPANTS: Ambulatory women aged 63 to 99 (N = 5,545). MEASUREMENTS:
      Minutes of MVPA per day measured using an accelerometer, functional status
      measured using the Short Physical Performance Battery (SPPB), fall risk factors
      assessed using a questionnaire, fall injuries assessed in a telephone interview,
      incident falls ascertained from fall calendars. RESULTS: Incident rate ratios
      (IRRs) revealed greater fall risk in women in the lowest quartile of MVPA
      compared to those in the highest (IRR = 1.18, 95% confidence interval = 1.01
      1.38), adjusted for age, race and ethnicity, and fall risk factors. Fall rates
      were not significantly associated with MVPA in women with high SPPB scores (9-12)
      or one or fewer falls in the previous year, but in women with low SPPB scores (<=
      8) or a history of frequent falls, fall rates were higher in women with lower
      MVPA levels than in those with higher levels (interaction P < .03 and < .001,
      respectively). Falls in women with MVPA above the median were less likely to
      involve injuries requiring medical treatment (9.9%) than falls in women with
      lower MVPA levels (13.0%) (P < .001). CONCLUSION: These findings indicate that
      falls are not more common or injurious in older women who engage in higher levels
      of MVPA. These findings support encouraging women to engage in the amounts and
      types of MVPA that they prefer. Older women with low physical function or
      frequent falls with low levels of MVPA are a high-risk group for whom vigilance
      about falls prevention is warranted.

PMID- 28755416
TI  - Hydrodynamic lift forces on solutes in a tilted nanopillar array: A computer
      simulation study.
AB  - We study solute transport in a microfluidic channel, where the walls hold an
      array of tilted rigid nanopillars. By solving numerically the flow equations in
      the channel, we show that a combination of hydrodynamic effects with excluded
      volume interactions between the solute particles and the pillars leads to a
      hydrodynamic lift effect, which varies with the particle size, and depends in a
      strongly nonlinear fashion on the flow rate. We show that the lift force can be
      sufficiently strong to drive the solute accumulation or removal from the pillar
      region and can be switched to the opposite direction by variation of the shear
      rate or driving pressure. We also demonstrate that the nanopillar array can be
      used to selectively attract particles of certain size and enhance solute trapping
      at the surface.

PMID- 28755417
TI  - What affects the predictability of evolutionary constraints using a G-matrix? The
      relative effects of modular pleiotropy and mutational correlation.
AB  - Phenotypic traits do not always respond to selection independently from each
      other and often show correlated responses to selection. The structure of a
      genotype-phenotype map (GP map) determines trait covariation, which involves
      variation in the degree and strength of the pleiotropic effects of the underlying
      genes. It is still unclear, and debated, how much of that structure can be
      deduced from variational properties of quantitative traits that are inferred from
      their genetic (co) variance matrix (G-matrix). Here we aim to clarify how the
      extent of pleiotropy and the correlation among the pleiotropic effects of
      mutations differentially affect the structure of a G-matrix and our ability to
      detect genetic constraints from its eigen decomposition. We show that the
      eigenvectors of a G-matrix can be predictive of evolutionary constraints when
      they map to underlying pleiotropic modules with correlated mutational effects.
      Without mutational correlation, evolutionary constraints caused by the fitness
      costs associated with increased pleiotropy are harder to infer from evolutionary
      metrics based on a G-matrix's geometric properties because uncorrelated
      pleiotropic effects do not affect traits' genetic correlations. Correlational
      selection induces much weaker modular partitioning of traits' genetic
      correlations in absence then in presence of underlying modular pleiotropy.

PMID- 28755418
TI  - A 13 C NMR method for determining secondary nitroxide-substrate associations.

PMID- 28755419
TI  - Quality assurance in proton beam therapy using a plastic scintillator and a
      commercially available digital camera.
AB  - PURPOSE: In this article, we evaluate a plastic scintillation detector system for
      quality assurance in proton therapy using a BC-408 plastic scintillator, a
      commercial camera, and a computer. METHODS: The basic characteristics of the
      system were assessed in a series of proton irradiations. The reproducibility and
      response to changes of dose, dose-rate, and proton energy were determined.
      Photographs of the scintillation light distributions were acquired, and compared
      with Geant4 Monte Carlo simulations and with depth-dose curves measured with an
      ionization chamber. A quenching effect was observed at the Bragg peak of the 60
      MeV proton beam where less light was produced than expected. We developed an
      approach using Birks equation to correct for this quenching. We simulated the
      linear energy transfer (LET) as a function of depth in Geant4 and found Birks
      constant by comparing the calculated LET and measured scintillation light
      distribution. We then used the derived value of Birks constant to correct the
      measured scintillation light distribution for quenching using Geant4. RESULTS:
      The corrected light output from the scintillator increased linearly with dose.
      The system is stable and offers short-term reproducibility to within 0.80%. No
      dose rate dependency was observed in this work. CONCLUSIONS: This approach offers
      an effective way to correct for quenching, and could provide a method for rapid,
      convenient, routine quality assurance for clinical proton beams. Furthermore, the
      system has the advantage of providing 2D visualization of individual radiation
      fields, with potential application for quality assurance of complex, time-varying
      fields.

PMID- 28755420
TI  - Cytobrush: A tool for sequential evaluation of gene expression in bovine
      endometrium.
AB  - Aims were to (i) compare specific transcript abundance between endometrial
      samples collected by transcervical biopsy and cytobrush and (ii) measure the
      abundance of endometrial transcripts involved in PGF2alpha synthesis in samples
      collected by cytobrush. In Experiment 1, endometrial samples were taken
      transcervically by cytobrush and biopsy 10 days after ovulation. Compared to
      biopsy samples, abundance of transcripts for MSTN, AKR1C4 and PGR was similar,
      VIM, FLT1 and PTGES was lower (p < .05) and KRT18 and CD3D was greater in
      cytobrush samples (p < .05). Thus, there was an enrichment of epithelial and
      immune cells in the cytobrush samples. In Experiment 2, endometrial samples were
      collected by cytobrush on days 10, 13, 16 and 19 after ovulation. Abundance of
      PGR2 mRNA was maximum on day 10 then decreased (p < .05). Abundance of ESR1
      decreased gradually from day 10 to day 16 then increased again on day 19. The
      greatest abundance of OXTR was noted on day 19. The sequential alterations in
      abundance of these transcripts are consistent with the release of PGF2alpha
      associated with luteolysis. In summary, cytobrush sampling provides
      representative, physiologically relevant samples of the luminal epithelium in
      cattle.

PMID- 28755421
TI  - Smoking is a risk factor for pulmonary metastasis in colorectal cancer.
AB  - AIM: The hepatic microenvironment, which may include chronic inflammation and
      fibrosis, is considered to contribute to the pathogenesis of liver metastases of
      colorectal cancer. A similar mechanism is anticipated for pulmonary metastases,
      although no reports are available. Smoking causes pulmonary inflammation and
      fibrosis. Thus, we hypothesized that smokers would be especially affected by
      pulmonary metastases of colorectal cancer. In this study, we attempted to clarify
      the impact of smoking on pulmonary metastasis of colorectal cancer. METHOD:
      Between September 2005 and December 2010 we reviewed 567 patients with
      pathological Stage I, II or III colorectal cancer, whose clinicopathological
      background included a preoperative smoking history, pack-year history from
      medical records. Univariate and multivariate analyses using the Cox proportional
      hazard model were performed to determine the independent prognostic factors for
      pulmonary metastasis-free survival. RESULTS: Pulmonary metastases occurred in 39
      (6.9%) patients. The smoking histories revealed 355 never smokers, 119 former
      smokers and 93 current smokers among the subjects. Multivariate analysis revealed
      that being a current smoker (hazard ratio = 2.72, 95% CI 1.18-6.25; P = 0.02) was
      an independent risk factor for pulmonary metastases. CONCLUSION: Smoking may be a
      risk factor for pulmonary metastasis of colorectal cancer. Cessation of smoking
      should be recommended to prevent pulmonary metastasis, although further basic and
      clinical studies are required.

PMID- 28755422
TI  - Diagnosis and management of endometriosis: a systematic review of international
      and national guidelines.
AB  - BACKGROUND: The development of clinical guidelines requires standardised methods
      informed by robust evidence synthesis. OBJECTIVES: We evaluated the
      methodological quality of endometriosis guidelines, mapped their recommendations,
      and explored the relationships between recommendations and research evidence.
      SEARCH STRATEGY: We searched EMBASE, MEDLINE, and PubMed from inception to
      February 2016. SELECTION CRITERIA: We included guidelines related to the
      diagnosis and management of endometriosis. DATA COLLECTION AND ANALYSIS: The
      search strategy identified 879 titles and abstracts. We include two international
      and five national guidelines. Four independent authors assessed the
      methodological quality of the included guidelines, using the Appraisal of
      Guidelines for Research & Evaluation (AGREE-II) instrument, and systematically
      extracted the guideline recommendations and supporting research evidence. MAIN
      RESULTS: One hundred and fifty-two different recommendations were made. Ten
      recommendations (7%) were comparable across guidelines. The European Society of
      Human Reproduction and Embryology was objectively evaluated as the highest
      quality guideline (methodological quality score: 88/100). There was substantial
      variation between the supporting evidence presented by individual guidelines for
      comparable recommendations. Forty-two recommendations (28%) were not supported by
      research evidence. No guideline followed the standardised guideline development
      methods (AGREE-II). CONCLUSIONS: There is substantial variation in the
      recommendations and methodological quality of endometriosis guidelines. Future
      guidelines should be developed with reference to high-quality methods in
      consultation with key stakeholders, including women with endometriosis, ensuring
      that their scope can truly inform clinical practice and eliminate unwarranted and
      unjustified variations in clinical practice. TWEETABLE ABSTRACT: #Endometriosis
      guidelines vary in recommendations and quality. @EndometriosisUK.

PMID- 28755423
TI  - Epac1, PDE4, and PKC protein expression and their association with AKAP95, Cx43,
      and cyclinD2/E1 in breast cancer tissues.
AB  - BACKGROUND: This study was conducted to investigate the exchange protein directly
      activated by cAMP (Epac1), PDE4, and PKC expression in breast cancer tissues, and
      the correlation between these proteins and AKAP95, Cx43, cyclin D2, and cyclin
      E1. METHODS: PV-9000 two-step immunohistochemistry was used to analyze protein
      expression. RESULTS: The positive rate of Epac1 protein expression in breast
      cancer tissues (58%) was higher than in para-carcinoma tissues (10%) (P < 0.05).
      There were no significant differences in the positive rates of PDE4 and PKC
      expression between breast cancer and para-carcinoma tissues (P > 0.05). The
      positive expression rate of PDE4 was higher in the P53 protein positive group
      compared to the P53 negative group (P < 0.05). Correlations between Epac1 and
      cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and
      PKC proteins were observed (P < 0.05). CONCLUSION: Epac1 expression in breast
      cancer tissues was increased, suggesting that the protein may be involved in the
      development of breast cancer. Correlations between Epac1 and cyclin D2, PDE4 and
      cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins suggested
      synergistic effects among these proteins in the development of breast cancer.

PMID- 28755424
TI  - Healthy Skin Wins: A Glowing Pressure Ulcer Prevention Program That Can Guide
      Evidence-Based Practice.
AB  - BACKGROUND: In 2013, an observational survey was conducted among 242 in-patients
      in a community hospital with a pressure ulcer (PU) prevalence of 34.3%. An
      evidence-based pressure ulcer prevention program (PUPP) was then implemented
      including a staff awareness campaign entitled "Healthy Skin Wins" with an online
      tutorial about PU prevention. AIMS: To determine the effectiveness of the PUPP in
      reducing the prevalence of PUs, to determine the effectiveness of the online
      tutorial in increasing hospital staff's knowledge level about PU prevention, and
      to explore frontline staff's perspectives of the PUPP. METHODS: This was a mixed
      methods study. A repeat observational survey discerned if the PUPP reduced PU
      prevalence. A pre-test post-test design was used to determine whether hospital
      staff's knowledge of PU prevention was enhanced by the online tutorial.
      Qualitative interviews were conducted with nurses, allied health professionals,
      and health care aides to explore staff's perspectives of the PUPP. RESULTS: A
      comparison of initial and repeat observational surveys (n = 239) identified a
      statistically significant reduction in the prevalence of PU to 7.53% (p < .001).
      The online tutorial enhanced staff knowledge level with a statistically
      significantly higher mean post-test score (n = 80). Thirty-five frontline staff
      shared their perspectives of the PUPP with "it's definitely a combination of
      everything" and "there's a disconnect between what's needed and what's available"
      as the main themes. CONCLUSIONS: Incorporating evidence-based PU prevention into
      clinical practice greatly reduced the prevalence of PUs among hospital in
      patients. Due to the small sample size for the pre-test post-test component, the
      effectiveness of the online tutorial in improving the knowledge level of PU
      prevention among hospital staff requires further research. LINKING EVIDENCE TO
      ACTION: Evidence-based PU prevention strategies are facilitated by using a
      multidisciplinary approach. Educational tools about PU prevention must target all
      members of the healthcare team including healthcare aides, patients and families.

PMID- 28755425
TI  - Accuracy of eight deformable image registration (DIR) methods for tomotherapy
      megavoltage computed tomography (MVCT) images.
AB  - INTRODUCTION: The application of deformable image registration (DIR) to
      megavoltage computed tomography (MVCT) images benefits adaptive radiotherapy.
      This study aims to quantify the accuracy of DIR for MVCT images when using
      different deformation methods assessed in a cubic phantom and nasopharyngeal
      carcinoma (NPC) patients. METHODS: In the control studies, the DIR accuracy in
      air-tissue and tissue-tissue interface areas was observed using twelve shapes of
      acrylic and tissue-equivalent material inserted in the phantom. In the clinical
      studies, the 1st and 20th fraction MVCT images of seven NPC patients were used to
      evaluate application of DIR. The eight DIR methods used in the DIRART software
      varied in (i) transformation framework (asymmetric or symmetric), (ii) DIR
      registration algorithm (Demons or Optical Flow) and (iii) mapping direction
      (forward or backward). The accuracy of the methods was compared using an
      intensity-based criterion (correlation coefficient, CC) and volume-based
      criterion (Dice's similarity coefficient, DSC). RESULTS: The asymmetric
      transformation with Optical Flow showed the best performance for air-tissue
      interface areas, with a mean CC and DSC of 0.97 +/- 0.03 and 0.79 +/- 0.11
      respectively. The symmetric transformation with Optical Flow showed good
      agreement for tissue-tissue interface areas with a CC of (0.99 +/- 0.01) and DSC
      of (0.89 +/- 0.03). The sequences of target domains were significantly different
      in tissue-tissue interface areas. CONCLUSIONS: The deformation method and
      interface area affected the accuracy of DIR. The validation techniques showed
      satisfactory volume matching of greater than 0.7 with DSC analysis. The methods
      can yield acceptable results for clinical applications.

PMID- 28755427
TI  - Pharmacokinetic Phenotyping to Predict Drug-Drug Interactions: Time to Divorce
      the Hybrid Concept of Simultaneous Mechanistic-Based and Exposure-Based
      Assessment.

PMID- 28755426
TI  - Radical hysterectomy after radiotherapy for recurrent or persistent cervical
      cancer.
AB  - OBJECTIVE: To evaluate the safety and efficacy of radical hysterectomy after
      radiotherapy (RH-AR) for recurrent or persistent cervical cancer. METHODS: The
      present retrospective study included patients who underwent RH-AR for recurrent
      or persistent cervical cancer at Osaka University Hospital, Japan, between May 1,
      2010 and September 30, 2016. Patient characteristics, intraoperative and
      postoperative adverse events, and surgical outcomes were investigated to identify
      patients at increased risk of recurrence or severe surgical adverse events.
      RESULTS: There were 31 patients scheduled for treatment with RH-AR; one
      hysterectomy procedure was aborted. No intraoperative adverse events or treatment
      related deaths occurred, and 8 (27%) patients experienced severe postoperative
      adverse events. After a median 34 months of follow-up, 13 (43%) patients had
      developed recurrent disease, predominantly at distant sites. The estimated 3-year
      overall survival rate was 53.8%. Positive surgical margins, nodal metastasis,
      parametrial invasion, and no adjuvant treatment after RH-AR were found to be
      predictors of increased risk of recurrence. No predictors of severe surgical
      adverse events were identified. CONCLUSION: RH-AR was a safe, curative treatment
      for patients with recurrent or persistent cervical cancer. However, considering
      the significant risk of surgical adverse events, RH-AR should only be performed
      for a select group of patients.

PMID- 28755428
TI  - Safely removing cell debris with LC3-associated phagocytosis.
AB  - Phagocytosis and autophagy are two distinct pathways that degrade external and
      internal unwanted particles. Both pathways lead to lysosomal degradation inside
      the cell, and over the last decade, the line between them has blurred; autophagy
      proteins were discovered on phagosomes engulfing foreign bacteria, leading to the
      proposal of LC3-associated phagocytosis (LAP). Many proteins involved in
      macroautophagy are used for phagosome degradation, although Atg8/LC3 family
      proteins only decorate the outer membrane of LC3-associated phagosomes, in
      contrast to both autophagosome membranes. A few proteins distinguish LAP from
      autophagy, such as components of the autophagy pre-initiation complex. However,
      most LAP cargo is wrapped in multiple layers of membranes, making them similar in
      structure to autophagosomes. Recent evidence suggests that LC3 is important for
      the degradation of internal membranes, explaining why LC3 would be a vital part
      of both macroautophagy and LAP. In addition to removing invading pathogens,
      multicellular organisms also use LAP to degrade cell debris, including cell
      corpses and photoreceptor outer segments. The post-mitotic midbody remnant is
      another cell fragment, which results from each cell division, that was recently
      added to the growing list of LAP cargoes. Thus, LAP plays an important role
      during the normal physiology and homoeostasis of animals.

PMID- 28755429
TI  - Identifying keystone habitats with a mosaic approach can improve biodiversity
      conservation in disturbed ecosystems.
AB  - Conserving native biodiversity in the face of human- and climate-related impacts
      is a challenging and globally important ecological problem that requires an
      understanding of spatially connected, organismal-habitat relationships. Globally,
      a suite of disturbances (e.g., agriculture, urbanization, climate change)
      degrades habitats and threatens biodiversity. A mosaic approach (in which
      connected, interacting collections of juxtaposed habitat patches are examined)
      provides a scientific foundation for addressing many disturbance-related,
      ecologically based conservation problems. For example, if specific habitat types
      disproportionately increase biodiversity, these keystones should be incorporated
      into research and management plans. Our sampling of fish biodiversity and aquatic
      habitat along ten 3-km sites within the Upper Neosho River subdrainage, KS, from
      June-August 2013 yielded three generalizable ecological insights. First, specific
      types of mesohabitat patches (i.e., pool, riffle, run, and glide) were physically
      distinct and created unique mosaics of mesohabitats that varied across sites.
      Second, species richness was higher in riffle mesohabitats when mesohabitat size
      reflected field availability. Furthermore, habitat mosaics that included more
      riffles had greater habitat diversity and more fish species. Thus, riffles (<5%
      of sampled area) acted as keystone habitats. Third, additional conceptual
      development, which we initiate here, can broaden the identification of keystone
      habitats across ecosystems and further operationalize this concept for research
      and conservation. Thus, adopting a mosaic approach can increase scientific
      understanding of organismal-habitat relationships, maintain natural biodiversity,
      advance spatial ecology, and facilitate effective conservation of native
      biodiversity in human-altered ecosystems.

PMID- 28755430
TI  - Alternative Saccharomyces interspecies hybrid combinations and their potential
      for low-temperature wort fermentation.
AB  - The lager yeast hybrid (Saccharomyces cerevisiae * Saccharomyces eubayanus)
      possesses two key characteristics that are essential for lager brewing: efficient
      sugar utilization and cold tolerance. Here we explore the possibility that the
      lager yeast phenotype can be recreated by hybridizing S. cerevisiae ale yeast
      with a number of cold-tolerant Saccharomyces species including Saccharomyces
      arboricola, Saccharomyces eubayanus, Saccharomyces mikatae and Saccharomyces
      uvarum. Interspecies hybrids performed better than parental strains in lager
      brewing conditions (12 degrees C and 12 degrees P wort), with the S. mikatae
      hybrid performing as well as the S. eubayanus hybrid. Where the S. cerevisiae
      parent was capable of utilizing maltotriose, this trait was inherited by the
      hybrids. A greater production of higher alcohols and esters by the hybrids
      resulted in the production of more aromatic beers relative to the parents. Strong
      fermentation performance relative to the parents was dependent on ploidy, with
      polyploid hybrids (3n, 4n) performing better than diploid hybrids. All hybrids
      produced 4-vinyl guaiacol, a smoke/clove aroma generally considered an off
      flavour in lager beer. This characteristic could however be eliminated by
      isolating spore clones from a fertile hybrid of S. cerevisiae and S. mikatae. The
      results suggest that S. eubayanus is dispensable when constructing yeast hybrids
      that express the typical lager yeast phenotype. (c) 2017 The Authors. Yeast
      published by John Wiley & Sons, Ltd.

PMID- 28755431
TI  - Herbicide-resistance mechanisms: gene amplification is not just for glyphosate.

PMID- 28755432
TI  - Multicavity Metallosupramolecular Architectures.
AB  - Discrete metallosupramolecular systems are often macrocyclic or cage-like
      architectures with an accessible internal cavity. Guest molecules can reside
      within these cavities and much of the interest in these systems is derived from
      these fascinating host-guest interactions. A range of potential applications stem
      from the ability of these metallosupramolecular architectures to encapsulate
      guests. These applications include catalysis or acting as molecular reaction
      flasks, the molecular scavenging of pollutants, storage of reactive species, and
      drug delivery. Multicavity metallosupramolecular architectures combine the
      ability of large hollow assemblies to bind multiple guests concurrently with the
      binding specificity associated with small cages. A variety of different
      approaches to generating separate compartments within a single
      metallosupramolecular assembly have emerged. These include interpenetrated cages,
      cages with polytopic ligands that have a long backbone, and molecules that have
      two or more clefts. This review examines these approaches, and highlights key
      contributions to the field.

PMID- 28755433
TI  - Postnatal Evaluation of Cervical Ribs in Control Rats.
AB  - BACKGROUND: Cervical ribs in rat fetuses have been widely reported to occur in
      controls as well as in response to various maternal chemical exposures. However,
      few evaluations of cervical ribs have been reported in rats postnatally. The
      available literature has indicated that the postnatal incidences of cervical ribs
      in control rats are no higher than in perinatal fetuses. METHODS: In a
      developmental toxicity study in rats conducted by the inhalation route, a control
      group of 44 time-mated female rats was exposed to filtered air only from
      gestation day (GD) 6 to 20, and divided into two cohorts. For one cohort, fetuses
      were removed from dams by laparohysterectomy for skeletal evaluation on GD 21.
      The other cohort of dams was permitted to deliver, and adult offspring were
      euthanized on postnatal day 65 for a subsequent postnatal skeletal evaluation of
      cervical ribs. RESULTS: The incidence of cervical ribs (mean percentage of
      affected fetuses or adults per litter) was observed to increase during postnatal
      development, from 1.0% on GD 21 to 12.7% on postnatal day 65. Further evaluation
      is ongoing to determine whether these observations were attributable to the
      inhalation exposure conditions used in this study. CONCLUSION: These results,
      while limited to the evaluation of one skeletal alteration in control rats,
      support the need for additional research into the area of postnatal development
      of skeletal abnormalities observed in developmental toxicity studies and the
      relevance of these skeletal observations to human risk assessment. Birth Defects
      Research 109:1301-1304, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28755434
TI  - Cross-Validation of the Minnesota Living With Heart Failure Questionnaire.
AB  - PURPOSE: The Minnesota Living With Heart Failure Questionnaire (MLHFQ) is the
      leading method for assessing quality of life in patients with heart failure (HF)
      around the world. However, unique, culture-specific variations in factorial
      structure have been identified. The current study examined the cross-cultural
      equivalence of an Italian version of the MLHFQ. DESIGN: Cross-sectional
      assessment as part of an HF study in Italy. Patients (n = 1,192; mean age = 72
      years, SD = 11) completed demographics, the MLHFQ, and the Short-Form 12 (SF-12).
      METHODS: A series of exploratory and confirmatory factor analyses were used to
      develop an appropriate factor model in the current sample. FINDINGS: We initially
      fit a confirmatory factor analysis based on published psychometric work
      validating the MLHFQ. This did not provide adequate fit, and the sample was then
      randomly split into equivalent subsets to conduct factor analyses with cross
      validation. In the first subsample, an exploratory factor analysis uncovered
      slight modifications to the proposed factor structure that resulted in much
      improved model fit. The final model included a higher order factor and three
      subscales: physical, emotional, and social. A cross-validation confirmatory
      factor analysis using this structure was conducted in the remaining subset to
      ensure broader applicability of the results. Correlations with the SF-12 were
      consistent with previous work using these measures. CONCLUSIONS: Some items of
      the MLHFQ are sensitive to differences across cultures, and factor structures
      vary based on where the scale is administered. In spite of these differences, the
      total score remains a valid and reliable indicator of quality of life in HF
      patients across cultures. CLINICAL RELEVANCE: Cultural influences on quality of
      life are important to consider when assessing patients' well-being in HF.

PMID- 28755435
TI  - The development and validation of EpiComet-Chip, a modified high-throughput comet
      assay for the assessment of DNA methylation status.
AB  - DNA damage and alterations in global DNA methylation status are associated with
      multiple human diseases and are frequently correlated with clinically relevant
      information. Therefore, assessing DNA damage and epigenetic modifications,
      including DNA methylation, is critical for predicting human exposure risk of
      pharmacological and biological agents. We previously developed a higher
      throughput platform for the single cell gel electrophoresis (comet) assay,
      CometChip, to assess DNA damage and genotoxic potential. Here, we utilized the
      methylation-dependent endonuclease, McrBC, to develop a modified alkaline comet
      assay, "EpiComet," which allows single platform evaluation of genotoxicity and
      global DNA methylation [5-methylcytosine (5-mC)] status of single-cell
      populations under user-defined conditions. Further, we leveraged the CometChip
      platform to create an EpiComet-Chip system capable of performing quantification
      across simultaneous exposure protocols to enable unprecedented speed and
      simplicity. This system detected global methylation alterations in response to
      exposures which included chemotherapeutic and environmental agents. Using
      EpiComet-Chip on 63 matched samples, we correctly identified single-sample
      hypermethylation (>=1.5-fold) at 87% (20/23), hypomethylation (>=1.25-fold) at
      100% (9/9), with a 4% (2/54) false-negative rate (FNR), and 10% (4/40) false
      positive rate (FPR). Using a more stringent threshold to define hypermethylation
      (>=1.75-fold) allowed us to correctly identify 94% of hypermethylation (17/18),
      but increased our FPR to 16% (7/45). The successful application of this novel
      technology will aid hazard identification and risk characterization of FDA
      regulated products, while providing utility for investigating epigenetic modes of
      action of agents in target organs, as the assay is amenable to cultured cells or
      nucleated cells from any tissue. Environ. Mol. Mutagen. 58:508-521, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28755436
TI  - Diagnostic accuracy of haptoglobin within ovarian cyst fluid as a potential point
      of-care test for epithelial ovarian cancer: an observational study.
AB  - OBJECTIVE: To investigate haptoglobin within ovarian cyst fluid (OCF) as a
      diagnostic biomarker for epithelial ovarian cancer (EOC) and develop an in vitro
      diagnostic point-of-care device test (IVDPCT) for use in the operating theatre.
      DESIGN: Retrospective and prospective cohort study. SETTING: South-East Asia.
      POPULATION: Women with suspicious ovarian cysts. METHODS: Proteomic,
      immunohistochemical and ELISA methods measured haptoglobin in OCF to
      differentiate benign and EOCs. Diagnostic performance of haptoglobin was compared
      with CA125, risk malignancy indices (RMI) and frozen section. Blinded validation
      of the IVDPCT was performed. MAIN OUTCOME MEASURES: Prediction of malignancy.
      RESULTS: Haptoglobin concentration measured by ELISA was 0.70 +/- 0.09 mg/ml in
      patients with benign cysts (n = 87), 6.22 +/- 0.53 mg/ml in early stage-EOC (n =
      17), and 6.57 +/- 0.65 mg/ml in late stage-EOC (n = 20). Haptoglobin in EOCs was
      significantly higher than in benign cysts (P < 0.0001). Haptoglobin using rapid
      colorimetric assay (RCA) on a training set had a sensitivity of 97.3% and a
      specificity 92.0%, comparable to ELISA and frozen sections. The haptoglobin AUROC
      curve was 0.999 (95% CI 0.997-1.000) compared with 0.895 (95% CI 0.814-0.977, P <
      0.05) for CA125. Haptoglobin performed significantly better than all the RMIs (P
      < 0.01). Blinded validation studies showed a minor drop in average diagnostic
      performance (sensitivity 85.2% and specificity 90.5%) compared with the training
      set. However, when compared with frozen section, haptoglobin was no worse in
      diagnostic accuracy for malignancy. CONCLUSION: Haptoglobin was identified as a
      biomarker for the detection of EOC with potential as a point-of-care diagnostic
      tool. TWEETABLE ABSTRACT: Haptoglobin within ovarian cyst fluid: a biomarker for
      epithelial ovarian cancer and point-of-care diagnostics.

PMID- 28755437
TI  - Phase contrast cell detection using multilevel classification.
AB  - In this paper, we propose a fully automated learning-based approach for detecting
      cells in time-lapse phase contrast images. The proposed system combines 2 machine
      learning approaches to achieve bottom-up image segmentation. We apply pixel-wise
      classification using random forests (RF) classifiers to determine the potential
      location of the cells. Each pixel is classified into 4 categories (cell, mitotic
      cell, halo effect, and background noise). Various image features are extracted at
      different scales to train the RF classifier. The resulting probability map is
      partitioned using the k-means algorithm to form potential cell regions. These
      regions are expanded into the neighboring areas to recover some missing or broken
      cell regions. To validate the cell regions, another machine learning method based
      on the bag-of-features and spatial pyramid encoding is proposed. The result of
      the second classifier can be a validated cell, a merged cell, or a noncell. In
      the case that the cell region is classified as a merged cell, it is split by
      using the seeded watershed method. The proposed method is demonstrated on several
      phase contrast image datasets, ie, U2OS, HeLa, and NIH 3T3. In comparison to
      state-of-the-art cell detection techniques, the proposed method shows improved
      performance, particularly in dealing with noise interference and drastic shape
      variations.

PMID- 28755438
TI  - Clinicopathological characteristics and prognosis of patients with multiple
      primary melanomas.

PMID- 28755439
TI  - alpha-Oxo-Ketenimines from Isocyanides and alpha-Haloketones: Synthesis and
      Divergent Reactivity.
AB  - The palladium-catalyzed reaction of alpha-haloketones with isocyanides afforded
      alpha-oxo-ketenimines through beta-hydride elimination of the beta-oxo-imidoyl
      palladium intermediates. Reaction of these relatively stable alpha-oxo
      ketenimines with nucleophiles such as hydrazines, hydrazoic acid, amines, and
      Grignard reagent afforded pyrazoles, tetrazole, beta-keto amidines, and
      enaminone, respectively, with high chemoselectivity. Whereas amines attack
      exclusively on the ketenimine functions, the formal [3+2] cycloaddition between N
      monosubstituted hydrazines and alpha-oxo-ketenimines was initiated by
      nucleophilic addition to the carbonyl group.

PMID- 28755440
TI  - The effectiveness of surgical interventions for women with FGM/C: a systematic
      review.
AB  - BACKGROUND: Female genital mutilation/cutting (FGM/C) changes normal genital
      functionality and can cause complications. There is an increasing demand for
      treatment of FGM/C-related complications. OBJECTIVES: We conducted a systematic
      review of empirical quantitative research on the outcomes of interventions for
      women with FGM/C-related complications. SEARCH STRATEGY: A search specialist
      searched 16 electronic databases. SELECTION CRITERIA: Selection was performed
      independently by two researchers. We accepted quantitative studies that examined
      the outcome of an intervention for an FGM/C-related concern. DATA COLLECTION AND
      ANALYSIS: We extracted data into a pre-designed form, calculated effect
      estimates, and performed meta-analyses. MAIN RESULTS: We included 62 studies
      (5829 women), which investigated the effect of defibulation, excision of cysts,
      and clitoral reconstruction. Meta-analyses of defibulation versus no defibulation
      showed a significantly lower risk of caesarean section (relative risk, RR: 0.33;
      95% confidence interval, 95% CI: 0.25-0.45) and perineal tears with defibulation:
      second-degree tear (RR: 0.44, 95% CI: 0.24-0.79), third-degree tear (RR: 0.21,
      95% CI: 0.05-0.94), fourth-degree tear (RR: 0.06, 95% CI: 0.01-0.41). The meta
      analyses detected no significant differences in obstetric outcomes of antenatal
      versus intrapartum defibulation. Except for one study, none of the studies on the
      excision of cysts indicated any complications, and the results were deemed
      favourable. Reconstructive surgery resulted in a visible clitoris in about 77% of
      women. Most women self-reported improvements in their sexual life, but up to 22%
      experienced a worsening in sexuality-related outcomes after reconstruction.
      CONCLUSIONS: Women with FGM/C who seek therapeutic surgery should be informed
      about the scarcity of evidence for benefits and the potential harms of the
      available procedures. TWEETABLE ABSTRACT: Systematic review shows defibulation
      after FGM/C has obstetric benefits; effect of reconstruction is uncertain.

PMID- 28755441
TI  - Plan quality and delivery time comparisons between volumetric modulated arc
      therapy and intensity modulated radiation therapy for scalp angiosarcoma: A
      planning study.
AB  - INTRODUCTION: Due to its spherical surface, scalp angiosarcoma requires careful
      consideration for radiation therapy planning and dose delivery. Herein, we
      investigated whether volumetric modulated arc therapy (VMAT) is superior to
      intensity modulated radiation therapy (IMRT) in terms of the plan quality and
      delivery time. METHODS: Three different coplanar treatment plans were created for
      four patients, comprising a two-arc VMAT plan as well as 5-field and 9-field IMRT
      plans with 6 MV beams. The X-ray Voxel Monte Carlo algorithm was employed for
      dose calculation. A radiation therapy dose of 60 Gy was prescribed to the
      planning target volume (PTV) in 30 fractions. The homogeneity indexes (HIs) and
      conformity indexes (CIs) of the PTV, organs at risk (OARs) doses and delivery
      times were calculated and compared. RESULTS: For the VMAT, 5-field and 9-field
      IMRT plans, the mean HIs were 0.14, 0.16 and 0.15; CIs100% were 0.63, 0.61 and
      0.64; CIs98% were 0.72, 0.66 and 0.70 and CIs95% were 0.74, 0.67 and 0.71
      respectively. All mean dose parameters of the VMAT and 9-field IMRT plans for the
      brain were equal to or lower than those of the 5-field IMRT plan. For the 5-field
      IMRT plan, the dose constraints for the left lens were not satisfied in two
      patients. The mean delivery times were 3.3, 11.1 and 14.7 min for the VMAT, 5
      field and 9-field IMRT plans respectively. CONCLUSION: The VMAT plan quality is
      comparable to that of 9-field IMRT, with a reduced delivery time. Therefore, VMAT
      represents a valuable, sophisticated irradiation technique for treating scalp
      angiosarcoma.

PMID- 28755442
TI  - Vacuolar processing enzyme activates programmed cell death in the apical meristem
      inducing loss of apical dominance.
AB  - The potato (Solanum tuberosum L.) tuber is a swollen underground stem that can
      sprout in an apical dominance (AD) pattern. Bromoethane (BE) induces loss of AD
      and the accumulation of vegetative vacuolar processing enzyme (S. tuberosum
      vacuolar processing enzyme [StVPE]) in the tuber apical meristem (TAM). Vacuolar
      processing enzyme activity, induced by BE, is followed by programmed cell death
      in the TAM. In this study, we found that the mature StVPE1 (mVPE) protein
      exhibits specific activity for caspase 1, but not caspase 3 substrates. Optimal
      activity of mVPE was achieved at acidic pH, consistent with localization of
      StVPE1 to the vacuole, at the edge of the TAM. Downregulation of StVPE1 by RNA
      interference resulted in reduced stem branching and retained AD in tubers treated
      with BE. Overexpression of StVPE1 fused to green fluorescent protein showed
      enhanced stem branching after BE treatment. Our data suggest that, following
      stress, induction of StVPE1 in the TAM induces AD loss and stem branching.

PMID- 28755443
TI  - Application of Liquid Biopsies in Cancer Targeted Therapy.
AB  - As a growing body of evidence demonstrates intertumoral and intratumoral
      heterogeneity and clonal evolution, both during carcinogenesis and also
      throughout treatment resulting in acquired drug resistance, the utility of blood
      based assays or "liquid biopsies" is becoming increasingly recognized in clinical
      practice and trial design. "Liquid biopsies" provide a less invasive approach to
      the current gold standard of interrogating tumors by tissue biopsies, which are
      frequently unfeasible, associated with morbidity, and cannot be performed as
      often.

PMID- 28755444
TI  - Bolusing frequency and amount impacts glucose control during hybrid closed-loop.
AB  - AIM: To compare bolus insulin delivery patterns during closed-loop home studies
      in adults with suboptimally [HbA1c 58-86 mmol/mol (7.5%-10%)] and well-controlled
      [58 mmol/mol (< 7.5%)] Type 1 diabetes. METHODS: Retrospective analysis of
      daytime and night-time insulin delivery during home use of closed-loop over 4
      weeks. Daytime and night-time controller effort, defined as amount of insulin
      delivered by closed-loop relative to usual basal insulin delivery, and daytime
      bolus effort, defined as total bolus insulin delivery relative to total daytime
      insulin delivery were compared between both cohorts. Correlation analysis was
      performed between individual bolus behaviour (bolus effort and frequency) and
      daytime controller efforts, and proportion of time spent within and below sensor
      glucose target range. RESULTS: Individuals with suboptimally controlled Type 1
      diabetes had significantly lower bolus effort (P = 0.038) and daily bolus
      frequency (P < 0.001) compared with those with well-controlled diabetes.
      Controller effort during both daytime (P = 0.007) and night-time (P = 0.005) were
      significantly higher for those with suboptimally controlled Type 1 diabetes. Time
      when glucose was within the target range (3.9-10.0 mmol/L) during daytime
      correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency
      (r = 0.33, P = 0.037). Time when glucose was below the target range during
      daytime was comparable in both groups (P = 0.36), and did not correlate
      significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = 
      0.21, P = 0.19). CONCLUSION: More frequent bolusing and higher proportion of
      insulin delivered as bolus during hybrid closed-loop use correlated positively
      with time glucose was in target range. This emphasises the need for user input
      and educational support to benefit from this novel therapeutic modality.

PMID- 28755445
TI  - Quantification of free fatty acids in human stratum corneum using tandem mass
      spectrometry and surrogate analyte approach.
AB  - The free fatty acids (FFAs) are one of the major components of the lipids in the
      stratum corneum (SC), the uppermost layer of the skin. Relative composition of
      FFAs has been proposed as a biomarker of the skin barrier status in patients with
      atopic dermatitis (AD). Here, we developed an LC-ESI-MS/MS method for
      simultaneous quantification of a range of FFAs with long and very long chain
      length in the SC collected by adhesive tape (D-Squame). The method, based on
      derivatization with 2-bromo-1-methylpyridinium iodide and 3-carbinol-1
      methylpyridinium iodide, allowed highly sensitive detection and quantification of
      FFAs using multiple reaction monitoring. For the quantification, we applied a
      surrogate analyte approach and internal standardization using isotope labeled
      derivatives of FFAs. Adhesive tapes showed the presence of several FFAs, which
      are also present in the SC, a problem encountered in previous studies. Therefore,
      the levels of FFAs in the SC were corrected using C12:0, which was present on the
      adhesive tape, but not detected in the SC. The method was applied to SC samples
      from patients with atopic dermatitis and healthy subjects. Quantification using
      multiple reaction monitoring allowed sufficient sensitivity to analyze FFAs of
      chain lengths C16-C28 in the SC collected on only one tape strip.

PMID- 28755446
TI  - The effect of a multidisciplinary regional educational programme on the quality
      of colon cancer resection.
AB  - AIM: Mesocolic plane surgery with central vascular ligation produces an
      oncologically superior specimen following colon cancer resection and appears to
      be related to optimal outcomes. We aimed to assess whether a regional educational
      programme in optimal mesocolic surgery led to an improvement in the quality of
      specimens. METHOD: Following an educational programme in the Capital and Zealand
      areas of Denmark, 686 cases of primary colon cancer resected across six hospitals
      were assessed by grading the plane of surgery and undertaking tissue morphometry.
      These were compared to 263 specimens resected prior to the educational programme.
      RESULTS: Across the region, the mesocolic plane rate improved from 58% to 77% (P
      < 0.001). One hospital had previously implemented optimal surgery as standard
      prior to the educational programme and continued to produce a high rate of
      mesocolic plane specimens (68%) with a greater distance between the tumour and
      the high tie (median for all fresh cases: 113 vs 82 mm) and lymph node yield (33
      vs 18) compared to the other hospitals. Three of the other hospitals showed a
      significant improvement in the plane of surgical resection. CONCLUSION: A
      multidisciplinary regional educational programme in optimal mesocolic surgery
      improved the oncological quality of colon cancer specimens as assessed by
      mesocolic planes; however, there was no significant effect on the amount of
      tissue resected centrally. Surgeons who attempt central vascular ligation
      continue to produce more radical specimens suggesting that such educational
      programmes alone are not sufficient to increase the amount of tissue resected
      around the tumour.

PMID- 28755447
TI  - Matches and mismatches between conservation investments and biodiversity values
      in the European Union.
AB  - Recently, the European Commission adopted a new strategy to halt the loss of
      biodiversity. Member states are expected to favor a more effective collection and
      redistribution of European Union (EU) funds under the current Multiannual
      Financial Framework for 2014-2020. Because of the large spatial variation in the
      distribution of biodiversity and conservation needs at the continental scale, EU
      instruments should ensure that countries with higher biodiversity values get more
      funds and resources for the conservation than other countries. Using linear
      regressions, we assessed the association between conservation investments and
      biodiversity values across member states, accounting for a variety of
      conservation investment indicators, taxonomic groups (including groups of plants,
      vertebrates, and invertebrates), and indicators of biodiversity value. In
      general, we found clear overall associations between conservation investments and
      biodiversity variables. However, some countries received more or less investment
      than would be expected based on biodiversity values in those countries. We also
      found that the extensive use of birds as unique indicators of conservation
      effectiveness may lead to biased decisions. Our results can inform future
      decisions regarding funding allocation and thus improve distribution of EU
      conservation funds.

PMID- 28755448
TI  - Short term in vivo precision of whole body composition measurements on the
      Horizon A densitometer.
AB  - INTRODUCTION: Dual-energy X-ray absorptiometry (DXA) is increasingly being used
      to assess abnormalities in body composition associated with a wide variety of
      conditions including obesity, sarcopenia, diabetes, anorexia, human
      immunodeficiency virus lipodystrophy, malabsorption and neuromuscular disorders.
      The objective of this study was to determine the short-term in vivo precision and
      least significant change in serial body composition measurements provided by the
      Hologic Horizon A densitometer as there is no published, peer reviewed body
      composition precision data on Horizon scanners in the medical literature.
      METHODS: After acquiring two new Hologic Horizon A densitometers, short term
      precision scanning was performed on the two scanners using different groups of 30
      volunteers, who had duplicate scans with all scans performed by the same
      operator. Using the International Society of Clinical Densitometry's advanced
      precision tool, the scan data were recorded and the coefficient of variation (CV)
      and least significant change (LSC) determined for total fat, lean and bone
      mineral content (BMC) and bone mineral density (BMD). RESULTS: Coefficients of
      variation of 0.78% and 0.77% were achieved for total fat (LSC at 95% confidence
      2.15%) and 0.52% and 0.40% for total lean (LSC at 95% confidence 1.45% and
      1.11%). CONCLUSIONS: These results indicate that the two Horizon A scanners in
      this study exceeded the minimum acceptable precision values by roughly a factor
      of four and are therefore capable of detecting small differences in lean and fat
      mass of 1-2% between two measurements at 95% confidence.

PMID- 28755449
TI  - Population structure and attribution of human clinical Campylobacter jejuni
      isolates from central Europe to livestock and environmental sources.
AB  - Campylobacter jejuni is among the most prevalent causes of human bacterial
      gastroenteritis worldwide. Domesticated animals and, especially, chicken meat are
      considered to be the main sources of infections. However, the contribution of
      surface waters and wildlife in C. jejuni transmission to humans is not well
      understood. We have evaluated the source attribution potential of a six-gene
      multiplex PCR (mPCR) method coupled with STRUCTURE analysis on a set of 410 C.
      jejuni strains isolated from environment, livestock, food and humans in central
      Europe. Multiplex PCR fingerprints were analysed using Subclade prediction
      algorithm to classify them into six distinct mPCR clades. A subset of C. jejuni
      isolates (70%) was characterized by multilocus sequence typing (MLST)
      demonstrating 74% congruence between mPCR and MLST. The correspondence analysis
      of mPCR clades and sources of isolation indicated three distinct groups in the
      studied C. jejuni population-the first one associated with isolates from poultry,
      the second one with isolates from cattle, and the third one with isolates from
      the environment. The STRUCTURE analysis attributed 7.2% and 21.7% of human
      isolates to environmental sources based on MLST and mPCR fingerprints,
      respectively.

PMID- 28755450
TI  - Men's perspectives on cancer prevention behaviors associated with HPV.
AB  - BACKGROUND: The human papillomavirus (HPV) is associated with the diagnosis of
      anal, penile, and oropharyngeal cancers in men. Evidence indicates that correct
      condom use in addition to obtaining the HPV vaccine provides the greatest
      protection from HPV infections. OBJECTIVE: To explore young men's beliefs and
      behavioral intention in relation to receiving the HPV vaccine and using a condom
      correctly and consistently for sexual contact. METHODS: A cross-sectional study
      underpinned by the theory of planned behavior (TPB) was conducted with male
      participants (n = 359, 18-28 years) who completed an online survey. Descriptive,
      correlational, and hierarchical regression analyses were performed on both status
      variables and variables of the TPB. RESULTS: Subjective norms (beta = 0.519, P <
      .001) was identified as the most influential predictor in relation to men's
      intention to receive the HPV vaccine, while relationship status (beta = -0.215, P
      < .001) and attitudes (beta = 0.394, P < .001) presented as the most significant
      predictors of intention to use a condom. Summarily, 51% of the variance in
      intention to receive the HPV vaccine and 44% in intention to use a condom were
      explained by the TPB model. CONCLUSION: Results from this study will impact on
      future sexual health research, education programs, and interventions for both HPV
      preventative behaviors towards the elimination of HPV-related cancers in men.

PMID- 28755451
TI  - Comparative effectiveness of antihypertensive drugs in nondiabetic patients with
      hypertension: A population-based study.
AB  - The authors compared the effectiveness of thiazide diuretic (TD), angiotensin
      converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and
      calcium channel blocker (CCB) monotherapies for the treatment of nondiabetic
      hypertension using MarketScan Databases 2010-2014. Multivariable Cox regression
      models assessed whether the addition of a new antihypertensive drug, treatment
      discontinuation, or switch and major cardiovascular or cerebrovascular events
      varied across groups. A total of 565 009 patients started monotherapy with ACEIs
      (43.6%), CCBs (23.6%), TDs (18.8%), or ARBs (14.0%). Patients who took TDs had a
      higher risk for either drug addition or discontinuation than patients who took
      ACEIs (hazard ratio [HR], 0.69 [95% CI, 0.68-0.70] vs HR, 0.81 [95% CI, 0.80
      0.81]), ARBs (HR, 0.67 [95% CI, 0.66-0.68] vs HR, 0.66 [95% CI, 0.65-0.67]), and
      CCBs (HR, 0.85 [95% CI, 0.84-0.87] vs HR, 0.94 [95% CI, 0.93-0.95]). Conversely,
      patients who took TDs experienced a lower risk of clinical events compared with
      patients who took ACEIs (HR, 1.24 [95% CI, 1.15-1.33]), ARBs (HR, 1.28 [95% CI,
      1.18-1.39]), and CCBs (HR, 1.35 [95% CI, 1.25-1.46]). Our results provide a
      strong rationale for choosing TDs as first-line monotherapy for the control of
      hypertension.

PMID- 28755452
TI  - Extrapolating evidence of antiepileptic drug efficacy in adults to children >=2
      years of age with focal seizures: The case for disease similarity.
AB  - Expediting pediatric access to new antiseizure drugs is particularly compelling,
      because epileptic seizures are the most common serious neurological symptom in
      children. Analysis of antiepileptic drug (AED) efficacy outcomes of randomized
      controlled trials, conducted during the past 20 years in different populations
      and a broad range of study sites and countries, has shown considerable
      consistency for each drug between adult and pediatric populations. Historically,
      the majority of regulatory approvals for AEDs have been for seizure types and not
      for specific epilepsy syndromes. Available data, both anatomical and
      neurophysiological, support a similar pathophysiology of focal seizures in adults
      and young children, and suggest that by age 2 years the structural and
      physiological milieu upon which seizures develop is similar. Although the
      distribution of specific etiologies and epilepsy syndromes is different in
      children from in adults, this should not impact approvals of efficacy based on
      seizure type, because the pathophysiology of focal seizures and the drug
      responsiveness of these seizure types are quite similar. Safety and
      pharmacokinetics cannot be extrapolated from adults to children. The scientific
      rationale, clinical consensus, and published data support a future approach
      accepting efficacy data from adult trials and focusing exclusively on prospective
      pharmacokinetic, tolerability, and safety studies and long-term follow-up in
      children. Whereas tolerability studies can be compared easily in children and
      adults, safety studies require large numbers of patients followed for many years.

PMID- 28755453
TI  - Frailty as a Risk Factor for Falls Among Community Dwelling People: Evidence From
      a Meta-Analysis.
AB  - PURPOSE: This study was conducted to investigate the relationships between
      different frailty stages and the fall incidence rates of community-dwelling older
      adults. The differences between various frailty indicators regarding assessment
      accuracy of the fall incidence rates of community-dwelling elders were also
      analyzed. Finally, the relationship between frailty and recurrent falls was
      explored. METHODS: This study comprised a systematic literature review and meta
      analysis. Two researchers independently examined and extracted the related
      literature. The key search terms included frailty, frail, fall, older people,
      older, geriatric, and senior. The literature sampling period was from January
      2001 to December 2016. The quality of each paper was assessed according to the
      guidelines of the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA). The databases of the Cochrane Library, Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), PubMed, and MEDLINE were used to
      conduct a systematic literature search by using the random effect mode to analyze
      the compiled papers. FINDINGS: A total of 102,130 community-dwelling older adults
      >=65 years of age and 33,503 older adults who had experienced a fall were
      compiled to investigate the relationship between frailty and falls. The meta
      analysis results revealed that compared with robust older adults, frail older
      adults demonstrated the greatest risk for falls, followed by prefrail older
      adults. Furthermore, the use of different frailty indicators to predict the fall
      incidence rates of older adults yielded nonsignificantly different outcomes. In
      short, studies of either cardiovascular health or osteoporotic fracture
      indicators are effective for predicting the risk for falls in older people.
      Finally, this study confirmed that compared with robust older adults, frail older
      adults were more likely to experience recurrent falls. CONCLUSIONS: Frailty is a
      crucial healthcare topic of people with geriatric syndromes. Frail older adults
      are likely to experience recurrent falls. In addition, the evidence-based study
      indicated that once older people enter the prefrail stage, they are likely to
      experience falls. Therefore, older adults should be evaluated for the possibility
      of geriatric syndromes such as frailty, which may be addressed to reduce the risk
      for bone fractures and death. CLINICAL RELEVANCE: Professional nurses should use
      frailty assessment indicators as early as possible to evaluate the possibility of
      frailty in community-dwelling older people. Meanwhile, effective frailty
      prevention strategies should be applied to prevent frailty, thereby reducing the
      incidence of falls and enhancing older persons' quality of life.

PMID- 28755454
TI  - Comorbid anxiety moderates the relationship between depression history and
      prefrontal EEG asymmetry.
AB  - The internalizing spectrum of psychiatric disorders-depression and anxiety-are
      common, highly comorbid, and challenging to treat. Individuals with childhood
      onset depression have a particularly poor prognosis. There is compelling evidence
      that individuals with depression display reduced resting-state EEG activity at
      sensors overlying the left prefrontal cortex, even during periods of remission,
      but it remains unknown whether this asymmetry is evident among individuals with a
      comorbid anxiety disorder. Here, we demonstrate that women with a history of
      childhood onset depression and no anxiety disorder (n = 37) show reduced left
      lateral frontal activity compared to psychiatrically healthy controls (n = 69).
      In contrast, women with a history of childhood onset depression and pathological
      levels of anxious apprehension (n = 18)-as indexed by a current generalized
      anxiety disorder, obsessive compulsive disorder, or separation anxiety disorder
      diagnosis-were statistically indistinguishable from healthy controls.
      Collectively, these observations suggest that anxious apprehension can mask the
      relationship between prefrontal EEG asymmetry and depression. These findings have
      implications for understanding (a) prefrontal EEG asymmetry as a
      neurophysiological marker of depression, (b) the comorbidity of depression and
      anxiety, and (c) failures to replicate the relationship between prefrontal EEG
      asymmetry and depression. More broadly, they set the stage for developing refined
      interventions for internalizing psychopathology.

PMID- 28755455
TI  - Radiosynthesis of 1-iodo-2-[11 C]methylpropane and 2-methyl-1-[11 C]propanol and
      its application for alkylation reactions and C-C bond formation.
AB  - The multitude of biologically active compounds requires the availability of a
      broad spectrum of radiolabeled synthons for the development of positron emission
      tomography (PET) tracers. The aim of this study was to synthesize 1-iodo-2-[11
      C]methylpropane and 2-methyl-1-[11 C]propanol and investigate the use of these
      reagents in further radiosynthesis reactions. 2-Methyl-1-[11 C]propanol was
      obtained with an average radiochemical yield of 46 +/- 6% d.c. and used with
      fluorobenzene as starting material. High conversion rates of 85 +/- 4% d.c. could
      be observed with HPLC, but large precursor amounts (32 mg, 333 MUmol) were
      needed. 1-Iodo-2-[11 C]methylpropane was synthesized with a radiochemical yield
      of 25 +/- 7% d.c. and with a radiochemical purity of 78 +/- 7% d.c. The labelling
      agent 1-iodo-2-[11 C]methylpropane was coupled to thiophenol, phenol and
      phenylmagnesium bromide. Average radiochemical conversions of 83% d.c. for
      thiophenol, 40% d.c. for phenol, and 60% d.c. for phenylmagnesium bromide were
      obtained. In addition, [11 C]2-methyl-1-propyl phenyl sulphide was isolated with
      a radiochemical yield of 5 +/- 1% d.c. and a molar activity of 346 +/- 113
      GBq/MUmol at the end of synthesis. Altogether, the syntheses of 1-iodo-2-[11
      C]methylpropane and 2-methyl-1-[11 C]propanol were achieved and applied as proof
      of their applicability.

PMID- 28755456
TI  - In Situ Localization of Enzyme Activity in Live Cells by a Molecular Probe
      Releasing a Precipitating Fluorochrome.
AB  - Current enzyme-responsive, fluorogenic probes fail to provide in situ information
      because the released fluorophores tend to diffuse away from the reaction sites.
      The problem of diffusive signal dilution can be addressed by designing a probe
      that upon enzyme conversion releases a fluorophore that precipitates. An excited
      state intramolecular proton transfer (ESIPT)-based solid-state fluorophore HTPQ
      was developed that is strictly insoluble in water and emits intense fluorescence
      in the solid state, with lambdaex/em =410/550 nm, thus making it far better
      suited to use with a commercial confocal microscope. HTPQ was further utilized in
      the design of an enzyme-responsive, fluorogenic probe (HTPQA), targeting alkaline
      phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion-resistant in
      situ detection of endogenous ALP in live cells. It was also employed in the
      visualizing of different levels of ALP in osteosarcoma cells and tissue, thus
      demonstrating its interest for the diagnosis of this type of cancer.

PMID- 28755457
TI  - Randomized, Controlled, Crossover trial of Prevention of Clindamycin-Induced
      Gastrointestinal Signs Using a Synbiotic in Healthy Research Cats.
AB  - BACKGROUND: Synbiotics often are prescribed to limit antibiotic-associated
      gastrointestinal signs (AAGS) in cats, but data to support this recommendation
      are lacking. OBJECTIVE: To determine whether synbiotic co-administration
      mitigates AAGS in healthy research cats treated with clindamycin. ANIMALS: 16
      healthy research cats. METHODS: A randomized, double-blinded, placebo-controlled,
      2-way, 2-period, crossover study with a 6-week washout was performed. Each study
      period consisted of a 1-week baseline and a 3-week treatment period. Cats
      received 75 mg clindamycin with food once daily for 3 weeks, followed 1 hour
      later by either 2 capsules of a synbiotic or placebo. Food consumption, vomiting,
      fecal score, and completion of treatment were compared using repeated measures
      split plot or crossover designs with covariates, with P < 0.05 considered
      significant. RESULTS: Cats that received the synbiotic were more likely to
      complete treatment in period 1 (100% vs. 50%, P = 0.04). Cats vomited less when
      receiving the synbiotic but this was not significant, but there were significant
      period effects (F-value = 11.4, P < 0.01). Cats had higher food intake while
      receiving the synbiotic (F-value = 31.1, P < 0.01) despite period effects (F
      value = 8.6, P < 0.01). There was no significant effect of treatment on fecal
      scores, which significantly increased over time (F-value = 17.9, P < 0.01).
      CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of a synbiotic 1 hour after
      clindamycin administration decreased hyporexia and vomiting in healthy cats.
      Additionally, significant period effects suggest that clinical benefits of
      synbiotic administration persist for at least 6 weeks after discontinuation,
      decreasing the severity of AAGS in cats that subsequently received clindamycin
      with placebo. Unlike in people, synbiotic administration did not decrease
      antibiotic-associated diarrhea.

PMID- 28755458
TI  - Tonic noradrenergic activity modulates explorative behavior and attentional set
      shifting: Evidence from pupillometry and gaze pattern analysis.
AB  - A constant task for every living organism is to decide whether to exploit rewards
      associated with current behavior or to explore the environment for more rewarding
      options. Current empirical evidence indicates that exploitation is related to
      phasic whereas exploration is related to tonic firing mode of noradrenergic
      neurons in the locus coeruleus. In humans, this exploration-exploitation trade
      off is subserved by the ability to flexibly switch attention between task-related
      and task-irrelevant information. Here, we investigated whether this function,
      called attentional set shifting, is related to exploration and tonic
      noradrenergic discharge. We measured pretrial baseline pupil dilation, proved to
      be strongly correlated with the activity of the locus coeruleus, while human
      participants took part in well-known tasks of attentional set shifting. Study 1
      used the Wisconsin Card Sorting Task, whereas in Study 2, the
      Intra/Extradimensional Set Shifting Task was used. Both tasks require
      participants to choose between different compound stimuli based on feedback
      provided for their previous decisions. During the task, stimulus-reward
      contingencies change periodically, thus participants are repeatedly required to
      reassess which stimulus features are relevant (i.e., they shift their attentional
      set). Our results showed that baseline pupil diameter steadily decreased when the
      stimulus-reward contingencies were stable, whereas they suddenly increased when
      these contingencies changed. Analysis of looking patterns also confirmed the
      presence of exploratory behavior during attentional set shifting. Thus, our
      results suggest that tonic firing mode of noradrenergic neurons in the locus
      coeruleus is implicated in attentional set shifting, as it regulates the amount
      of exploration.

PMID- 28755460
TI  - Pnictogen (As, Sb, Bi) Nanosheets for Electrochemical Applications Are Produced
      by Shear Exfoliation Using Kitchen Blenders.
AB  - Layered materials are of high importance because of their anisotropy and as a
      source of 2D materials. Whilst there is a plethora of multi-elemental 2D
      materials, the number mono-elemental 2D materials is rather limited. Herein, we
      demonstrate that aqueous shear exfoliation can be used to obtain As, Sb, and Bi
      exfoliated nanosheets. Morphological and chemical characterization of the
      exfoliated materials shows a decrease in thickness, sheet-to-nanosheet scale, and
      partial oxidation owing to a higher surface area. The electrochemical performance
      is tested in terms of inherent electrochemistry, electron transfer, and sensing
      applications as demonstrated with ascorbic acid. Potential energy-related
      applications are evaluated in the hydrogen evolution reaction (HER), oxygen
      evolution reaction (OER), and oxygen reduction reaction (ORR), with shear
      exfoliated Sb having the best electrochemical performance overall. These findings
      will have a profound impact on the preparation and application of 2D mono
      elemental materials.

PMID- 28755459
TI  - Defining definitions: a Delphi study to develop a core outcome set for conditions
      of severe maternal morbidity.
AB  - OBJECTIVE: Develop a core outcome set of international consensus definitions for
      severe maternal morbidities. DESIGN: Electronic Delphi study. SETTING:
      International. POPULATION: Eight expert panels. METHODS: All 13 high-income
      countries represented in the International Network of Obstetric Surveillance
      Systems (INOSS) nominated five experts per condition of morbidity, who submitted
      possible definitions. From these suggestions, a steering committee distilled
      critical components: eclampsia: 23, amniotic fluid embolism: 15, pregnancy
      related hysterectomy: 11, severe primary postpartum haemorrhage: 19, uterine
      rupture: 20, abnormally invasive placentation: 12, spontaneous haemoperitoneum in
      pregnancy: 16, and cardiac arrest in pregnancy: 10. These components were
      assessed by the expert panel using a 5-point Likert scale, following which a
      framework for an encompassing definition was constructed. Possible definitions
      were evaluated in rounds until a rate of agreement of more than 70% was reached.
      Expert commentaries were used in each round to improve definitions. MAIN OUTCOME
      MEASURES: Definitions with a rate of agreement of more than 70%. RESULTS: The
      invitation to participate in one or more of eight Delphi processes was accepted
      by 103 experts from 13 high-income countries. Consensus definitions were
      developed for all of the conditions. CONCLUSION: Consensus definitions for eight
      morbidity conditions were successfully developed using the Delphi process. These
      should be used in national registrations and international studies, and should be
      taken up by the Core Outcomes in Women's and Newborn Health initiative. TWEETABLE
      ABSTRACT: Consensus definitions for eight morbidity conditions were successfully
      developed using the Delphi process.

PMID- 28755461
TI  - Variation in organ-specific PIK3CA and KRAS mutant levels in normal human tissues
      correlates with mutation prevalence in corresponding carcinomas.
AB  - Large-scale sequencing efforts have described the mutational complexity of
      individual cancers and identified mutations prevalent in different cancers. As a
      complementary approach, allele-specific competitive blocker PCR (ACB-PCR) is
      being used to quantify levels of hotspot cancer driver mutations (CDMs) with high
      sensitivity, to elucidate the tissue-specific properties of CDMs, their
      occurrence as tumor cell subpopulations, and their occurrence in normal tissues.
      Here we report measurements of PIK3CA H1047R mutant fraction (MF) in normal
      colonic mucosa, normal lung, colonic adenomas, colonic adenocarcinomas, and lung
      adenocarcinomas. We report PIK3CA E545K MF measurements in those tissues, as well
      as in normal breast, normal thyroid, mammary ductal carcinomas, and papillary
      thyroid carcinomas. We report KRAS G12D and G12V MF measurements in normal colon.
      These MF measurements were integrated with previously published ACB-PCR data on
      KRAS G12D, KRAS G12V, and PIK3CA H1047R. Analysis of these data revealed a
      correlation between the degree of interindividual variability in these mutations
      (as log10 MF standard deviation) in normal tissues and the frequencies with which
      the mutations are detected in carcinomas of the corresponding organs in the
      COSMIC database. This novel observation has important implications. It suggests
      that interindividual variability in mutation levels of normal tissues may be used
      as a metric to identify mutations with critical early roles in tissue-specific
      carcinogenesis. Additionally, it raises the possibility that personalized cancer
      therapeutics, developed to target specifically activated oncogenic products,
      might be repurposed as prophylactic therapies to reduce the accumulation of cells
      carrying CDMs and, thereby, reduce future cancer risk. Environ. Mol. Mutagen.
      58:466-476, 2017. (c) 2017 This article is a U.S. Government work and is in the
      public domain in the USA. Environmental and Molecular Mutagenesis published by
      Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

PMID- 28755462
TI  - Exploring the screening capacity of the Fear of Cancer Recurrence Inventory-Short
      Form for clinical levels of fear of cancer recurrence.
AB  - OBJECTIVE: Fear of cancer recurrence (FCR) is a common concern among cancer
      survivors. Identifying survivors with clinically significant FCR requires
      validated screening measures and clinical cut-offs. We evaluated the Fear of
      Cancer Recurrence Inventory-Short Form (FCRI-SF) clinical cut-off in 2 samples.
      METHODS: Level of FCR in study 1 participants (from an Australian randomized
      controlled trial: ConquerFear) was compared with FCRI-SF scores. Based on a
      biopsychosocial interview, clinicians rated participants as having nonclinical,
      subclinical, or clinical FCR. Study 2 participants (from a Canadian FCRI-English
      validation study) were classified as having clinical or nonclinical FCR by using
      the semistructured clinical interview for FCR (SIFCR). Receiver operating
      characteristic analyses evaluated the screening ability of the FCRI-SF against
      clinician ratings (study 1) and the SIFCR (study 2). RESULTS: In study 1, 167
      cancer survivors (mean age: 53 years, SD = 10.1) participated. Clinicians rated
      43% as having clinical FCR. In study 2, 40 cancer survivors (mean age: 68 years,
      SD = 7.0) participated; 25% met criteria for clinical FCR according to the SIFCR.
      For both studies 1 and 2, receiver operating characteristic analyses suggested a
      cut-off >=22 on the FCRI-SF identified cancer survivors with clinical levels of
      FCR with adequate sensitivity and specificity. CONCLUSIONS: Establishing clinical
      cut-offs on FCR screening measures is crucial to tailoring individual care and
      conducting rigorous research. Our results suggest using a higher cut-off on the
      FCRI-SF than previously reported to identify clinically significant FCR.
      Continued evaluation and validation of the FCRI-SF cut-off is required across
      diverse cancer populations.

PMID- 28755463
TI  - Placental abruption in parents who were born small: registry-based cohort study.
AB  - OBJECTIVE: To assess whether parents who were born small for gestational age
      (below the 10th birthweight centile, SGA) have increased risk of severe or mild
      placental abruption. To assess whether a history of SGA in other family members
      modifies this intergenerational effect. DESIGN: Prospective population-based
      observational study. SETTING: The Medical Birth Registry of Norway. POPULATION:
      From 1967 to 2013, 785 333 mother-offspring pairs, 643 066 father-offspring
      pairs, 272 941 maternal tetrads (i.e. her offspring, sibling, and niece/nephew),
      and 265 505 paternal tetrads were identified. METHODS: Cohort study based on
      linked data from the Medical Birth Registry of Norway. MAIN OUTCOME MEASURES:
      Relative risk (RR) of severe placental abruption (preterm birth, birthweight
      below the 10th centile, or perinatal death) and mild placental abruption (other
      cases) in families with SGA. RESULTS: Mothers who were born SGA had increased
      risk of severe placental abruption (RR 1.5; 95% confidence interval, 95% CI 1.3
      1.8), but not mild abruption. The paternal effects were weaker. The combined
      effect of SGA in the mother and her sibling on severe abruption was twofold (RR
      2.4; 95% CI 1.7-3.3) compared with birthweight centiles >=10 for both. Similarly,
      the effect of adding an SGA niece/nephew was twofold (RR 2.3; 95% CI 1.3-3.9),
      whereas the combined effect of SGA in the mother, her sibling and her
      niece/nephew was fourfold (RR 3.6; 95% CI 1.9-6.8). CONCLUSIONS: Women who were
      born SGA have an increased risk of severe placental abruption. The corresponding
      paternal effect was modest. A history of SGA in other family members increases
      the generational effect. TWEETABLE ABSTRACT: Women born small for gestational age
      have excess risk of placental abruption.

PMID- 28755464
TI  - Acetyl-CoA carboxylase overexpression in herbicide-resistant large crabgrass
      (Digitaria sanguinalis).
AB  - BACKGROUND: The occurrence of herbicide-resistant weed biotypes is increasing and
      this report of an acetyl-CoA carboxylase (ACCase) inhibitor-resistant Digitaria
      sanguinalis L. Scop. from southwestern Ontario is another example. The identified
      weed escaped control in an onion and carrot rotation in which graminicides were
      used for several consecutive years. Our goal was to characterize the level and
      mechanism of resistance of the biotype. RESULTS: The biotype was resistant to all
      five ACCase inhibitor herbicides tested. Gene-expression profiling was performed
      because none of the mutations known to confer resistance in the ACCase gene were
      detected. RNASeq and quantitative reverse-transcriptase PCR (qRT-PCR) results
      indicated that transcription of ACCase was 3.4-9.3 times higher in the resistant
      biotype than the susceptible biotype. ACCase gene copy number was determined by
      qPCR to be five to seven times higher in the resistant compared with the
      susceptible biotype. ACCase gene overexpression was directly related to the
      increase of the ACCase gene copy number. CONCLUSION: Our results are consistent
      with the hypothesis that overexpression of the herbicide target gene ACCase
      confers resistance to the herbicide. This is the first reported case of target
      gene duplication conferring resistance to a herbicide other than glyphosate. (c)
      2017 Society of Chemical Industry See related Article.

PMID- 28755465
TI  - Can patients with chronic rhinosinusitis recover normal sleep after endoscopic
      sinus surgery?

PMID- 28755466
TI  - Hypospadias, Intrauterine Growth Restriction, and Abnormalities of the Placenta.
AB  - BACKGROUND: Hypospadias is more common among male infants with growth
      restriction, defined as a birth weight less than the 10th centile, than in
      infants with a normal birth weight. Intrauterine growth retardation (IUGR) has
      been associated, also, with abnormalities of the placenta, such as maternal
      vascular malperfusion. In a consecutive sample of newborn infants, the
      association between hypospadias, IUGR and abnormalities of the placenta could be
      analyzed. METHODS: Affected infants were identified among 289,365 liveborn and
      stillborn infants in the Active Malformations Surveillance Program between 1972
      and 2012. The four anatomic locations of the ectopic urethral opening, based on
      the recorded physical examination findings, were: (1) glandular; (2) subcoronal;
      (3) penile; (4) penoscrotal. Affected infants with associated malformations, a
      chromosome abnormality, teratogenic exposure, maternal diabetes mellitus, or
      multiple gestations were excluded. RESULTS: Three hundred sixteen affected
      infants were identified: 52.2% glandular, 11.7% subcoronal, 27.8% penile, and
      8.2% penoscrotal. The highest frequency of IUGR (34.6%) was in the infants with
      the most severe hypospadias (penoscrotal). The 39 reports of placenta findings
      showed a high frequency of abnormalities. CONCLUSION: An increased rate of
      occurrence of hypospadias and abnormalities of the placenta were present in
      infants with intrauterine growth restriction. The postulated cause of this
      association is a deficiency in the function of the placenta during weeks 10 to 14
      of gestation when normal masculinization occurs due to an increase in the level
      of placental human chorionic gonadotropin and fetal testosterone. The cause of
      the placental deficiency has not been established. Birth Defects Research 110:122
      127, 2018.(c) 2017 Wiley Periodicals, Inc.

PMID- 28755467
TI  - Connexin-43 and aquaporin-4 are markers of ageing-related tau astrogliopathy
      (ARTAG)-related astroglial response.
AB  - AIMS: Ageing-related tau astrogliopathy (ARTAG) appears in subependymal, subpial,
      perivascular, white matter (WM) and grey matter (GM) locations. Physical effects,
      blood-brain barrier dysfunction and blood- or vessel-related factors have been
      considered as aetiology. As connexin-43 (Cx43) and aquaporin-4 (AQP4) are related
      to these, we hypothesized that their immunoreactivity (IR) varies with ARTAG in a
      location-specific manner. METHODS: We performed a morphometric
      immunohistochemical study measuring the densities of IR of Cx43, AQP4, AT8
      (phospho-tau) and glial fibrillar acidic protein (GFAP). We analysed the amygdala
      and hippocampus in age-matched cases with (n = 19) and without (n = 20) ARTAG in
      each of the locations it aggregates. RESULTS: We show a dramatic increase (>6
      fold; P < 0.01) of Cx43 density of IR in ARTAG cases correlating strongly with
      AT8 density of IR, irrespective of the presence of neuronal tau pathology or
      reactive gliosis measured by GFAP density of IR, in the GM. In contrast, AQP4
      density of IR was increased only in the WM and GM, and was associated with
      increased AT8 density of IR only in WM and perivascular areas. DISCUSSION: Our
      study reveals distinctive astroglial responses in each of the locations
      associated with ARTAG. Our observations support the concept that factors related
      to brain-fluid interfaces and water-ion imbalances most likely play a role in the
      generation of ARTAG. As Cx43 is crucial for maintaining neuronal homeostasis, the
      ARTAG-dependent increase of Cx43 density of IR suggests that the development of
      ARTAG in the GM most likely indicates an early response to the degeneration of
      neurons.

PMID- 28755468
TI  - Association between Gallbladder Ultrasound Findings and Bacterial Culture of Bile
      in 70 Cats and 202 Dogs.
AB  - BACKGROUND: Bacterial cholecystitis often is diagnosed by combination of
      gallbladder ultrasound (US) findings and positive results of bile culture. The
      value of gallbladder US in determining the likelihood of bile bacterial infection
      in cats and dogs with suspected biliary disease is unknown.
      HYPOTHESIS/OBJECTIVES: To determine the value of gallbladder US in predicting
      bile bacterial culture results, identify most common bacterial isolates from
      bile, and describe complications after cholecystocentesis in cats and dogs with
      suspected hepatobiliary disease. ANIMALS: Cats (70) and dogs (202) that underwent
      an abdominal US and submission of bile for culture were included in the study.
      METHODS: A cross-sectional study design was used to determine the association of
      gallbladder US abnormalities and the results of bile cultures, and complications
      of cholecystocentesis. RESULTS: Abnormal gallbladder US had high sensitivity
      (96%) but low specificity (49%) in cats with positive and negative results of
      bile bacterial culture, respectively. Cats with normal gallbladder US findings
      were unlikely to have positive bile bacterial culture (negative predictive value
      of 96%). Gallbladder US had lower sensitivity (81%), specificity (31%), positive
      predictive value (20%), and negative predictive value (88%) in dogs. The most
      common bacterial isolates were of enteric origin, the prevalence being higher in
      cats. Incidence of complications after cholecystocentesis was 3.4%. CONCLUSIONS
      AND CLINICAL IMPORTANCE: Gallbladder US has a high negative predictive value for
      bile culture results in cats. This modality is less predictive of infection in
      dogs. Percutaneous US-guided cholecystocentesis has a low complication rate.

PMID- 28755469
TI  - A randomized controlled trial to evaluate the effects of dietary fibre from
      distillers grains on enterohemorrhagic Escherichia coli detection from the
      rectoanal mucosa and hides of feedlot steers.
AB  - Feeding high levels (>=40% dry matter) of distillers grains may increase the risk
      for cattle to carry enterohemorrhagic Escherichia coli (EHEC) O157. The mechanism
      for the increased risk is not known nor whether non-O157 EHEC are similarly
      affected. Our objective was to test whether the fibre content or other components
      of modified distillers grains plus solubles (MDGS) affects the probability for
      cattle to carry EHEC serogroups of public health importance. A 2 * 2 plus 1
      factorial treatment arrangement within a randomized block design was utilized.
      Within each of four blocks, 25 feedlot pens (n = 8 steers/pen) were assigned
      randomly to (i) corn-based control diet; (ii) 20% dry matter (DM) MDGS; (iii) 40%
      DM MDGS; (iv) corn bran added to corn-based diet to match fibre of 20% MDGS or
      (v) 40% MDGS. Rectoanal mucosa swabs (RAMS) were collected on day (d)0, d35, d70
      and d105; hide swabs were collected on the last feeding day. Samples were tested
      for EHEC by a molecular screening assay. The effects of fibre source and fibre
      level on EHEC carriage were tested using multilevel logistic regression
      (generalized linear mixed models; alpha = 0.05). EHEC O45 RAMS detection was
      associated with fibre level, source and sampling day. EHEC O103 RAMS detection
      increased by feeding 40% MDGS but not the corresponding corn bran diet. Hide
      contamination by EHEC O45 or O103 was less likely in cattle fed MDGS compared to
      corn bran diets. EHEC O111 RAMS detection decreased by feeding 40% MDGS but not
      by feeding the corresponding corn bran diet. Detection of EHEC O157 or O145 was
      not associated with dietary factors. Feeding 40% MDGS increased the probability
      for carriage of some EHEC serogroups but decreased probability of others, which
      indicated that EHEC serogroups have different risk factors associated with
      feeding MDGS and little association with dietary fibre.

PMID- 28755471
TI  - Mechanical loading disrupts osteocyte plasma membranes which initiates
      mechanosensation events in bone.
AB  - Osteocytes sense loading in bone, but their mechanosensation mechanisms remain
      poorly understood. Plasma membrane disruptions (PMD) develop with loading under
      physiological conditions in many cell types (e.g., myocytes, endothelial cells).
      These PMD foster molecular flux across cell membranes that promotes tissue
      adaptation, but this mechanosensation mechanism had not been explored in
      osteocytes. Our goal was to investigate whether PMD occur and initiate consequent
      mechanotransduction in osteocytes during physiological loading. We found that
      osteocytes experience PMD during in vitro (fluid flow) and in vivo (treadmill
      exercise) mechanical loading, in proportion to the level of stress experienced.
      In fluid flow studies, osteocyte PMD preferentially formed with rapid as compared
      to gradual application of loading. In treadmill studies, osteocyte PMD increased
      with loading in weight bearing locations (tibia), but this trend was not seen in
      non-weight bearing locations (skull). PMD initiated osteocyte mechanotransduction
      including calcium signaling and expression of c-fos, and repair rates of these
      PMD could be enhanced or inhibited pharmacologically to alter downstream
      mechanotransduction and osteocyte survival. PMD may represent a novel
      mechanosensation pathway in bone and a target for modifying skeletal adaptation
      signaling in osteocytes. (c) 2017 Orthopaedic Research Society. Published by
      Wiley Periodicals, Inc. J Orthop Res 36:653-662, 2018.

PMID- 28755470
TI  - The role of mechanobiology in progression of rotator cuff muscle atrophy and
      degeneration.
AB  - Rotator cuff (RC) muscles undergo several detrimental changes following
      mechanical unloading resulting from RC tendon tear. In this review, we highlight
      the pathological causes and consequences of mechanical alterations at the whole
      muscle, muscle fiber, and muscle resident cell level as they relate to RC disease
      progression. In brief, the altered mechanical loads associated with RC tear lead
      to architectural, structural, and compositional changes at the whole-muscle and
      muscle fiber level. At the cellular level, these changes equate to direct
      disruption of mechanobiological signaling, which is exacerbated by mechanically
      regulated biophysical and biochemical changes to the cellular and extra-cellular
      environment (also known as the stem cell "niche"). Together, these data have
      important implications for both pre-clinical models and clinical practice. In pre
      clinical models, it is important to recapitulate both the atrophic and
      degenerative muscle loss found in humans using clinically relevant modes of
      injury. Clinically, understanding the mechanics and underlying biology of the
      muscle will impact both surgical decision-making and rehabilitation protocols, as
      interventions that may be good for atrophic muscle will have a detrimental effect
      on degenerating muscle, and vice versa. (c) 2017 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 36:546-556, 2018.

PMID- 28755472
TI  - Impact of Managers' Coaching Conversations on Staff Knowledge Use and Performance
      in Long-Term Care Settings.
AB  - BACKGROUND: Extended lifespans and complex resident care needs have amplified
      resource demands on nursing homes. Nurse managers play an important role in staff
      job satisfaction, research use, and resident outcomes. Coaching skills, developed
      through leadership skill-building, have been shown to be of value in nursing.
      AIMS: To test a theoretical model of nursing home staff perceptions of their work
      context, their managers' use of coaching conversations, and their use of
      instrumental, conceptual and persuasive research. METHODS: Using a two-group
      crossover design, 33 managers employed in seven Canadian nursing homes were
      invited to attend a 2-day coaching development workshop. Survey data were
      collected from managers and staff at three time points; we analyzed staff data (n
      = 333), collected after managers had completed the workshop. We used structural
      equation modeling to test our theoretical model of contextual characteristics as
      causal variables, managers' characteristics, and coaching behaviors as mediating
      variables and staff use of research, job satisfaction, and burnout as outcome
      variables. RESULTS: The theoretical model fit the data well (chi2 = 58, df = 43,
      p = .06) indicating no significant differences between data and model-implied
      matrices. Resonant leadership (a relational approach to influencing change) had
      the strongest significant relationship with manager support, which in turn
      influenced frequency of coaching conversations. Coaching conversations had a
      positive, non-significant relationship with staff persuasive use of research,
      which in turn significantly increased instrumental research use. Importantly,
      coaching conversations were significantly, negatively related to job
      satisfaction. LINKING EVIDENCE TO ACTION: Our findings add to growing research
      exploring the role of context and leadership in influencing job satisfaction and
      use of research by healthcare practitioners. One-on-one coaching conversations
      may be difficult for staff not used to participating in such conversations.
      Resonant leadership, as expected, has a significant impact on manager support and
      job satisfaction among nursing home staff.

PMID- 28755473
TI  - Personalized treatment of severe atopic dermatitis in a child: A 10-year follow
      up.

PMID- 28755474
TI  - Controlling localization of Escherichia coli populations using a two-part
      synthetic motility circuit: An accelerator and brake.
AB  - Probiotics, whether taken as capsules or consumed in foods, have been regarded as
      safe for human use by regulatory agencies. Being living cells, they serve as
      "tunable" factories for the synthesis of a vast array of beneficial molecules.
      The idea of reprogramming probiotics to act as controllable factories, producing
      potential therapeutic molecules under user-specified conditions, represents a new
      and powerful concept in drug synthesis and delivery. Probiotics that serve as
      drug delivery vehicles pose several challenges, one being targeting (as seen with
      nanoparticle approaches). Here, we employ synthetic biology to control swimming
      directionality in a process referred to as "pseudotaxis." Escherichia coli,
      absent the motility regulator cheZ, swim sporadically, missing the traditional
      "run" in the run:tumble swimming paradigm. Upon introduction of cheZ in trans and
      its signal-generated upregulation, engineered bacteria can be "programmed" to
      swim toward the source of the chemical cue. Here, engineered cells that encounter
      sufficient levels of the small signal molecule pyocyanin, produce an engineered
      CheZ and swim with programmed directionality. By incorporating a degradation tag
      at the C-terminus of CheZ, the cells stop running when they exit spaces
      containing pyocyanin. That is, the engineered CheZ modified with a C-terminal
      extension derived from the putative DNA-binding transcriptional regulator YbaQ
      (RREERAAKKVA) is consumed by the ClpXP protease machine at a rate sufficient to
      "brake" the cells when pyocyanin levels are too low. Through this process, we
      demonstrate that over time, these engineered E. coli accumulate in pyocyanin-rich
      locales. We suggest that such approaches may find utility in engineering
      probiotics so that their beneficial functions can be focused in areas of
      principal benefit.

PMID- 28755475
TI  - Prostate epithelium basement membrane and prostate cell biology: 20 years.

PMID- 28755476
TI  - Regulation of the interaction between the neuronal BIN1 isoform 1 and Tau
      proteins - role of the SH3 domain.
AB  - Bridging integrator 1 (bin1) gene is a genetic determinant of Alzheimer's disease
      (AD) and has been reported to modulate Alzheimer's pathogenesis through
      pathway(s) involving Tau. The functional impact of Tau/BIN1 interaction as well
      as the molecular details of this interaction are still not fully resolved. As a
      consequence, how BIN1 through its interaction with Tau affects AD risk is also
      still not determined. To progress in this understanding, interaction of Tau with
      two BIN1 isoforms was investigated using Nuclear Magnetic Resonance spectroscopy.
      1 H, 15 N spectra showed that the C-terminal SH3 domain of BIN1 isoform 1
      (BIN1Iso1) is not mobile in solution but locked with the core of the protein. In
      contrast, the SH3 domain of BIN1 isoform 9 (BIN1Iso9) behaves as an independent
      mobile domain. This reveals an equilibrium between close and open conformations
      for the SH3 domain. Interestingly, a 334-376 peptide from the clathrin and AP-2
      binding domain (CLAP) domain of BIN1Iso1, which contains a SH3-binding site, is
      able to compete with BIN1-SH3 intramolecular interaction. For both BIN1 isoforms,
      the SH3 domain can interact with Tau(210-240) sequence. Tau(210-240) peptide can
      indeed displace the intramolecular interaction of the BIN1-SH3 of BIN1Iso1 and
      form a complex with the released domain. The measured Kd were in agreement with a
      stronger affinity of Tau peptide. Both CLAP and Tau peptides occupied the same
      surface on the BIN1-SH3 domain, showing that their interaction is mutually
      exclusive. These results emphasize an additional level of complexity in the
      regulation of the interaction between BIN1 and Tau dependent of the BIN1
      isoforms.

PMID- 28755477
TI  - Thioredoxin-interacting protein induced alpha-synuclein accumulation via
      inhibition of autophagic flux: Implications for Parkinson's disease.
AB  - AIMS: Thioredoxin-interacting protein (TXNIP) is associated with activation of
      oxidative stress through inhibition of thioredoxin (Trx). However, some evidences
      point out that TXNIP acts as a scaffolding protein in signaling complex
      independent of cellular redox regulation. The autophagy-lysosomal pathway plays
      important roles in the clearance of misfolded proteins and dysfunctional
      organelles. Lysosomal dysfunction has been involved in several neurodegenerative
      disorders including Parkinson's disease (PD). Although researchers have reported
      that TXNIP inhibited autophagic flux, the specific mechanism is rarely studied.
      METHODS: In this study, we investigated the effects of TXNIP on autophagic flux
      and alpha-synuclein accumulation by Western blot in HEK293 cells transfected with
      TXNIP plasmid. Further, we explored the influence of TXNIP on DA neuron survival
      in substantia nigra by IHC. RESULTS: We found that TXNIP induced LC3-II
      expression, but failed to degrade p62, a substrate of autophagy. Also, TXNIP
      aggravated alpha-synuclein accumulation. We also found that TXNIP inhibited the
      expression of ATP13A2, a lysosomal membrane protein. Moreover, we found that
      overexpression of ATP13A2 attenuated the impairment of autophagic flux and alpha
      synuclein accumulation induced by TXNIP. Furthermore, overexpression of TXNIP in
      substantia nigra resulted in loss of DA neuron. CONCLUSION: Our data suggested
      that TXNIP blocked autophagic flux and induced alpha-synuclein accumulation
      through inhibition of ATP13A2, indicating TXNIP was a disease-causing protein in
      PD.

PMID- 28755478
TI  - Characteristics of people with high visit-to-visit glycaemic variability in Type
      2 diabetes.
AB  - AIMS: Increased visit-to-visit glycaemic variability is independently associated
      with adverse outcomes in Type 2 diabetes. Our aim was to identify the patient
      characteristics associated with raised visit-to-visit glycaemic variability in
      people with Type 2 diabetes. METHODS: A case-control study was conducted to
      establish associations between HbA1c variability and clinical covariates in 10
      130 people with Type 2 diabetes. Variability was calculated by two metrics [sd
      and coefficient of variation (CV)] from a minimum of four HbA1c readings obtained
      over a 4-year period. High and low variability groups were defined as the top and
      bottom tertile of the sd or CV, and used in logistic regression analyses
      including a number of clinical and biochemical covariates. The analyses were
      stratified into low mean (< 53 mmol/mol; 7%) and high mean (>= 53 mmol/mol; 7%)
      HbA1c groups. RESULTS: Findings were consistent across both HbA1c groups and
      variability metrics. Treatment, independent of other factors, was the most
      strongly associated covariate for the risk of high HbA1c variability. A six-fold
      increased risk was observed in the low HbA1c group, between the most and least
      intense treatment regimens (P < 0.001). Similar findings were present in the high
      HbA1c group with a three-fold increase in risk (P < 0.001). In addition, male
      gender, younger age, reduced HDL-cholesterol and increased BMI were all found to
      be independently associated with raised visit-to-visit glycaemic variability.
      CONCLUSIONS: Intensive treatment resulting in low mean HbA1c was associated with
      marked increase in HbA1c variability. Irrespective of diabetes control, the
      greatest visit-to-visit variability was observed in young, insulin resistant men.

PMID- 28755479
TI  - Identifying exposition to low oxygen environment in human macrophages using
      secondary ion mass spectrometry and multivariate analysis.
AB  - RATIONALE: Macrophages are innate immune cells presenting a strong phenotypic
      plasticity and deeply involved in tissue homeostasis. Oxygen environmental
      tension is a physical parameter that could influence their polarizations. In this
      study we use time-of-flight secondary ion mass spectrometry (TOF-SIMS) to
      describe how various polarizations are modified by a low oxygen exposure.
      METHODS: TOF-SIMS experiments were performed using an IONTOF ToF-SIMS 5-100 (ION
      TOF GmbH, Munster, Germany). Analysis was performed using a pulsed 25 keV Bi3+
      beam, sputtering was performed using a 250 eV Cs beam. Cells were fixed by
      paraformaldehyde before TOF-SIMS analysis. RESULTS: Multivariate analysis of the
      TOF-SIMS spectra provided ion species associated with the exposure of macrophages
      to low oxygen concentration. We were able to obtain some species, specific of a
      particular polarization, advocating for the use of macrophages as reporter cells
      of oxygen tension in tissues. CONCLUSIONS: Our study demonstrates that macrophage
      molecular signature to low oxygen environment is dependent on their polarization.
      TOF-SIMS shows the clear capability to produce species revealing this exposition.
      This result opens the way to the use of TOF-SIMS as a tool to explore hypoxia in
      human tissues.

PMID- 28755480
TI  - G3BP1 interacts directly with the FMDV IRES and negatively regulates translation.
AB  - RNA-protein interactions play a pivotal role in the function of picornavirus
      internal ribosome entry site (IRES) elements. Here we analysed the impact of Ras
      GTPase SH3 domain binding protein 1 (G3BP1) in the IRES activity of foot-and
      mouth disease virus (FMDV). We found that G3BP1 interacts directly with three
      distinct sequences of the IRES element using RNA electrophoretic mobility-shift
      assays. Analysis of the interaction with domain 5 indicated that the G3BP1
      binding-site is placed at the single-stranded region although it allows large
      sequence heterogeneity and the hairpin located upstream of this region enhances
      retarded complex formation. In addition, G3BP1 interacts directly with the
      polypyrimidine tract-binding protein and the translation initiation factor 4B
      (eIF4B) through the C-terminal region. Moreover, G3BP1 is cleaved during FMDV
      infection yielding two fragments, Ct-G3BP1 and Nt-G3BP1. Both fragments inhibit
      cap- and IRES-dependent translation, but the Ct-G3BP1 fragment shows a stronger
      effect on IRES-dependent translation. Assembly of complexes with G3BP1 results in
      a significantly reduced local flexibility of the IRES element, consistent with
      the negative effect of this protein. Our results highlight the IRES-binding
      capacity of G3BP1 and illustrate its function as a translation inhibitor.

PMID- 28755481
TI  - A Comparison of the Incidence of Post-Dural Puncture Headache and Backache After
      Spinal Anesthesia: A Pragmatic Randomized Controlled Trial.
AB  - BACKGROUND: Although bed rest is recommended after spinal anesthesia to prevent
      the occurrence of post-dural puncture headache, current literature suggests that
      periods of bed rest did not prevent headache as well as increase the risk of
      other complications such as backache. However, information is scarce regarding an
      appropriate period of bed rest following a dural puncture. AIM: The aim of this
      study was to compare the incidence of post-dural puncture headache and backache
      after different periods of bed rest following spinal anesthesia. METHODS: This
      study was a pragmatic, parallel-group, blinded, and randomized controlled trial
      (trial registration number KCT0001797). A total of 119 patients who underwent
      surgery under spinal anesthesia participated in this study from December 2013 to
      June 2014. The participants were randomly allocated to three groups: the
      immediate mobilization group (n = 45), 4-hour bed rest group (n = 40), and 6-hour
      bed rest group (n = 34). The severity of headache and backache was measured using
      the Dittmann scale and a visual analogue scale, respectively. Data were collected
      for 5 consecutive days postoperatively by one researcher blind to the group
      allocation. RESULTS: No significant difference in the incidence of headache among
      the three groups was detected. However, the incidence of backache in the 6-hour
      bed rest group was higher and was significantly more severe than the other
      groups. LINKING EVIDENCE TO ACTION: Bed rest after spinal anesthesia did not
      prevent the occurrence of headache and increased the incidence of patients
      experiencing a backache and, therefore, is not recommended. The findings provide
      information for establishing evidence-based nursing practices for patients after
      a dural puncture.

PMID- 28755482
TI  - Bax, Bak and beyond - mitochondrial performance in apoptosis.
AB  - Bax and Bak are members of the Bcl-2 family and core regulators of the intrinsic
      pathway of apoptosis. Upon apoptotic stimuli, they are activated and oligomerize
      at the mitochondrial outer membrane (MOM) to mediate its permeabilization, which
      is considered a key step in apoptosis. However, the molecular mechanism
      underlying Bax and Bak function has remained a key question in the field. Here,
      we review recent structural and biophysical evidence that has changed our
      understanding of how Bax and Bak promote MOM permeabilization. We also discuss
      how the spatial regulation of Bcl-2 family preference for binding partners
      contributes to regulate Bax and Bak activation. Finally, we consider the
      contribution of mitochondrial composition, dynamics and interaction with other
      organelles to apoptosis commitment. A new perspective is emerging, in which the
      control of apoptosis by Bax and Bak goes beyond them and is highly influenced by
      additional mitochondrial components.

PMID- 28755483
TI  - Constitutive Expression of Chimeric Transcription Factors Enables Cellulase
      Synthesis under Non-Inducing Conditions in Penicillium oxalicum.
AB  - Industrial production of cellulase by filamentous fungi is largely dependent on
      cellulose, which serves as a natural inducer of cellulase expression. However,
      insoluble cellulose is unfavorable to submerged fermentation and thus limits the
      production level of cellulase. The possibility of cellulase production under non
      inducing conditions is explored in Penicillium oxalicum by overexpressing two
      chimeric transcription factors. The chimeric transcription factors contain the
      DNA binding domain of cellulase transcriptional activator ClrB linked to the C
      terminal sequences of XlnRA871V , a constitutively active mutant of hemicellulase
      transcriptional activator. The obtained recombinant mutants exhibited
      dramatically improved basal production of cellulase, which was not observed with
      the overexpression of intact ClrB. When cultivated in a complex cellulosic
      medium, one of these mutants, OE-CXC -S-1, displayed a 7.3-fold increase in
      cellulase production (2.8 U mL-1 ) relative to the parent strain. The results
      demonstrate that the dependence of cellulase synthesis on cellulose could be
      reduced by the overexpression of artificially designed chimeric transcription
      factors, and offers a potential strategy to engineer fungal strains for improving
      cellulase production.

PMID- 28755484
TI  - Duration of life-cycle toxicity tests with the ostracod Heterocypris incongruens.
AB  - An acute sediment toxicity test using the ostracod Heterocypris incongruens is
      user friendly and has high sensitivity; however, a life-cycle test using this
      species has not been developed. The most challenging problem when developing a
      life-cycle test is that the egg development time varies greatly and is sometimes
      too long (> 150 d) to monitor. It is desirable to shorten the duration of life
      cycle toxicity tests including the observation period of egg development while
      preserving the ecological relevance of the net reproductive rate (R0 ), an
      endpoint in the life-cycle test. Therefore, in the present study, we suggest a
      practical test duration for R0 using population growth rate (lambda) as a measure
      of ecological relevance. We collected a range of life history characteristics of
      the ostracod by combining data from the literature and experimental results,
      constructed population matrix models, and calculated lambda for 20 life history
      patterns. The results showed that a longer test period (> 150 d) did not increase
      the correlation coefficients between R0 and lambda. Rather, a shorter test
      duration resulted in R0 being highly correlated with lambda. Our results suggest
      that a life-cycle toxicity test using the ostracod can provide an ecologically
      relevant toxicity endpoint, even if the test is abandoned after approximately 50
      d and unhatched eggs remain. Environ Toxicol Chem 2017;36:3443-3449. (c) 2017
      SETAC.

PMID- 28755485
TI  - Opposing effects of low versus high concentrations of water soluble
      vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells
      (CSCs).
AB  - Colorectal cancer is one of the global causes of cancer deaths. Cancer stem cells
      (CSCs) inside the tumour niche responsible for metastasis and relapses, and hence
      need to be targeted for cancer therapeutics. Although dietary fibre and lifestyle
      changes have been recommended as measures for colorectal cancer prevention, no
      such recommendations are available for using water soluble vitamins as
      prophylaxis measure for colorectal cancers. High dose of Vitamin C has been
      proven to selectively kill colon cancer cells having BRAF and KRAS mutations by
      inducing oxidative stress. In this study, we show for the first time the opposing
      effects of the low and high dose of Vitamin C and vitamin B3 on colon CSCs
      isolated from HT-29 and HCT-15 colorectal carcinoma cell lines. At small doses,
      both of these vitamins exerted a cell proliferative effect only on CSCs, while
      there was no change in the proliferation status of non-stem cancer cells and wild
      type (WT) populations. On the other hand, the death effects induced by high doses
      of Vitamin C and B3 were of the order of 50-60% and ~30% on CSCs from HT-29 and
      HCT15, respectively. Interestingly, the control fibroblast cell line (NIH3T3) was
      highly refractory all the tested concentrations of Vitamin C and B3, except for
      the highest dose - 10,000 MUg of Vitamin C that induced only 15% of cell death.
      Hence, these results indicate the future scope of use of therapeutic doses of
      Vitamin C and B3 especially in patients with advanced colorectal cancer.

PMID- 28755486
TI  - NMR investigation of water diffusion in different biofilm structures.
AB  - Mass transfer in biofilms is determined by diffusion. Different mostly invasive
      approaches have been used to measure diffusion coefficients in biofilms, however,
      data on heterogeneous biomass under realistic conditions is still missing. To non
      invasively elucidate fluid-structure interactions in complex multispecies
      biofilms pulsed field gradient-nuclear magnetic resonance (PFG-NMR) was applied
      to measure the water diffusion in five different types of biomass aggregates: one
      type of sludge flocs, two types of biofilm, and two types of granules. Data
      analysis is an important issue when measuring heterogeneous systems and is shown
      to significantly influence the interpretation and understanding of water
      diffusion. With respect to numerical reproducibility and physico-chemical
      interpretation, different data processing methods were explored: (bi)-exponential
      data analysis and the Gamma distribution model. Furthermore, the diffusion
      coefficient distribution in relation to relaxation was studied by D-T2 maps
      obtained by 2D inverse Laplace transform (2D ILT). The results show that the
      effective diffusion coefficients for all biofilm samples ranged from 0.36 to 0.96
      relative to that of water. NMR diffusion was linked to biofilm structure (e.g.,
      biomass density, organic and inorganic matter) as observed by magnetic resonance
      imaging and to traditional biofilm parameters: diffusion was most restricted in
      granules with compact structures, and fast diffusion was found in heterotrophic
      biofilms with fluffy structures. The effective diffusion coefficients in the
      biomass were found to be broadly distributed because of internal biomass
      heterogeneities, such as gas bubbles, precipitates, and locally changing biofilm
      densities. Thus, estimations based on biofilm bulk properties in multispecies
      systems can be overestimated and mean diffusion coefficients might not be
      sufficiently informative to describe mass transport in biofilms and the near
      bulk.

PMID- 28755487
TI  - A translational neuroscience approach to body image disturbance and its
      remediation in anorexia nervosa.
AB  - Deviant perception of the body is a fundamental component of anorexia nervosa.
      Here we offer a potential mechanistic explanation that involves perturbations
      within the visual system and the brain circuits that modulate perceptual
      organization. Based on the model proposed, we also suggest a mechanistic strategy
      for altering neuronal activity in the visual system to normalize perception of
      the body, and set out a strategy for empirically testing its clinical
      application.

PMID- 28755488
TI  - Bilateral quadriceps and hamstrings muscle volume asymmetries in healthy
      individuals.
AB  - Determining the magnitude of quadriceps and hamstring muscle volume asymmetries
      in healthy individuals is a critical first step toward interpreting asymmetries
      as compensatory or abnormal in pathological populations. The purpose of this
      study was to determine the magnitude of whole and individual muscle volume
      asymmetries, quantified as right-left volume differences, for the quadriceps and
      hamstring muscles in a young and healthy population. Twenty-one healthy
      individuals participated: Eleven females age = 22.6 +/- 2.9 years and 10 males
      age = 23.2 +/- 3.4 years. Whole muscle group and individual muscle volume
      asymmetries were quantified within the context of absolute measurement error
      using a 95% Limits of Agreement approach. Mean muscle asymmetries ranged from 
      3.0 to 6.0% for all individual and whole muscle groups. Whole muscle group 95%
      limits of agreements represented +/-11.4% and +/-8.8% volume asymmetries for the
      hamstrings and quadriceps, respectively. Individual muscle asymmetry 95% limits
      of agreements ranged from ~ +/- 11-13% for the vastii muscles while the biceps
      femoris short-head (+/-33.5%), long-head (+/-20.9%), and the rectus femoris (+/
      21.4%) displayed the highest relative individual asymmetries. Individual muscle
      asymmetries exceeded absolute measurement error in 70% of all cases, with 26% of
      all cases exceeding 10% asymmetry. Although whole muscle group asymmetries appear
      to be near the 10% assumed clinical threshold of normality, the greater magnitude
      of individual muscle asymmetries highlights the subject- and muscle-specific
      variability in volume asymmetry. Future research is warranted to determine if
      volume asymmetry thresholds exist that discriminate between healthy and
      pathological populations. Statement of Clinical Significance: Muscle volume
      asymmetries displayed in healthy individuals provide a reference for interpreting
      asymmetries in pathological populations. (c) 2017 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 36:963-970, 2018.

PMID- 28755489
TI  - Vernal freeze damage and genetic variation alter tree growth, chemistry, and
      insect interactions.
AB  - Anticipated consequences of climate change in temperate regions include early
      spring warmup punctuated by intermittent hard freezes. Warm weather accelerates
      leaf flush in perennial woody species, potentially exposing vulnerable young
      tissues to damaging frosts. We employed a 2 * 6 randomized factorial design to
      examine how the interplay of vernal (springtime) freeze damage and genetic
      variation in a hardwood species (Populus tremuloides) influences tree growth,
      phytochemistry, and interactions with an insect herbivore (Chaitophorus
      stevensis). Acute effects of freezing included defoliation and mortality.
      Surviving trees exhibited reduced growth and altered biomass distribution.
      Reflushed leaves on these trees had lower mass per area, lower lignin
      concentrations, and higher nitrogen concentrations, altered chemical defence
      profiles, and supported faster aphid population growth. Many effects varied among
      plant genotypes and were related with herbivore performance. This study suggests
      that a single damaging vernal freeze event can alter tree-insect interactions
      through effects on plant growth and chemistry. Differential responses of various
      genotypes to freeze damage suggest that more frequent vernal freeze events could
      also influence natural selection, favouring trees with greater freeze hardiness,
      and more resistance or tolerance to herbivores following damage.

PMID- 28755491
TI  - Systematic Review of Psychosocial Interventions for People With Spinal Cord
      Injury During Inpatient Rehabilitation: Implications for Evidence-Based Practice.
AB  - BACKGROUND: The bio-psychosocial model of spinal cord injury (SCI) highlights
      that psychosocial care is of equal importance as physical rehabilitation, and
      should be offered in the earlier stages of inpatient rehabilitation. AIM: This
      systematic review aimed to identify interventional research regarding
      psychosocial care for people with SCI during inpatient rehabilitation and
      synthesize the evidence of the effects and characteristics of these studies.
      METHODS: A systematic search of relevant literature published between 1985 to
      July 2016 was conducted with six databases (Scopus, MEDLINE, CINAHL, Science
      Citation Index Expanded, PsycINFO, and the China Academic Journal Full-text
      Database). Reference lists of the identified articles were reviewed to find
      additional relevant articles. RESULTS: A total of four randomized controlled
      trials and seven non-randomized controlled trials were included in this review.
      The interventions focused on specialized types of SCI population with relatively
      high levels of psychological distress, pain or pressure ulcers. Studies reported
      some varied or inconsistent improvements in participants' cognitive appraisal,
      psychosocial adaptation or mental health but there were no significant effects on
      their coping ability. Due to the heterogeneity of the studies, findings were
      synthesized narratively without conducting meta-analysis. LINKING EVIDENCE TO
      ACTION: This review found promising evidence that approaches to psychosocial care
      for people with SCI can improve their cognitive appraisal and psychosocial
      adaptation. Significant methodological limitations weakened study findings.
      Additionally, because studies were conducted in only a few developed countries
      with subgroups of patients having specific illness characteristics or severity,
      their generalizability to the wider SCI population is uncertain. Therefore,
      future research should adopt more robust study designs to test psychosocial
      interventions for SCI patients with different socio-cultural backgrounds and
      psychological adjustment conditions in the early stages of rehabilitation.

PMID- 28755490
TI  - Metabolic engineering of isopropyl alcohol-producing Escherichia coli strains
      with 13 C-metabolic flux analysis.
AB  - Metabolic engineering of isopropyl alcohol (IPA)-producing Escherichia coli
      strains was conducted along with 13 C-metabolic flux analysis (MFA). A
      metabolically engineered E. coli strain expressing the adc gene derived from
      Clostridium acetobutylicum and the IPADH gene from C. beijerinckii did not
      produce IPA during its exponential growth phase in the aerobic batch culture. 13
      C-MFA was carried out, and revealed a deficiency in NADPH regeneration for IPA
      production in growth phase. Based on these findings, we used nitrogen-starved
      culture conditions to reduce NADPH consumption for biomass synthesis. As a
      result, IPA yield was increased to 20% mol/mol glucose. 13 C-MFA revealed that
      the relative flux levels through the oxidative pentose phosphate (PP) pathway and
      the TCA cycle were elevated in nitrogen-starved condition relative to glucose
      uptake rate. To prevent CO2 release in the 6-phosphogluconate dehydrogenase
      (6PGDH) reaction, metabolism of this E. coli strain was further engineered to
      redirect glycolytic flux to the glucose 6-phosphate dehydrogenase (G6PDH) and
      Entner-Doudoroff (ED) pathway. IPA yield of 55% mol/mol glucose was achieved by
      combining the nitrogen-starved culture condition with the metabolic redirection.
      The 13 C-MFA data and intracellular NADPH levels obtained under these IPA
      production conditions revealed linear correlations between the specific IPA
      production rate and NADPH concentration, as well as between IPA yield and the
      pyruvate dehydrogenase (PDH) flux. Our results showed that 13 C-MFA is a helpful
      tool for metabolic engineering studies, and that further improvement in IPA
      production by E. coli may be achieved by fine-tuning the cofactor ratio and
      concentrations, as well as optimizing the metabolic pathways and culture
      conditions.

PMID- 28755492
TI  - Comparison of fatigue, depression, and anxiety as factors affecting posttreatment
      health-related quality of life in lung cancer survivors.
AB  - OBJECTIVE: To compare the effects of fatigue, anxiety, and depression on health
      related quality of life (HRQoL) in survivors of surgically resectable lung
      cancer. METHODS: In total, 830 lung cancer survivors participated in the study.
      They completed a questionnaire consisting of items pertaining to sociodemographic
      characteristics, clinical variables, and HRQoL. We calculated prevalence rates
      for fatigue, anxiety, and depression and performed multiple logistic regression
      and general linear modeling to determine the main factors affecting HRQoL.
      RESULTS: The prevalence rates for moderate fatigue (Brief Fatigue Inventory mean
      score: >=4), borderline depression (Hospital Anxiety and Depression Scale
      Depression score: >=8), and borderline anxiety (Hospital Anxiety and Depression
      Scale-Anxiety score: >=8) were 42.2%, 38.9%, and 20.9%, respectively. The main
      factor was fatigue, which demonstrated the strongest explanatory power for HRQoL
      including all 5 functional HRQoL components (ie, physical, role, emotional,
      cognitive, and social functioning) and global health status (partial R2 range:
      .13 to .19). However, anxiety (partial R2  = .21) and fatigue (partial R2  = .19)
      both demonstrated strong explanatory power for emotional HRQoL. In addition,
      depression demonstrated weak explanatory power for HRQoL including emotional
      HRQoL. CONCLUSIONS: Relative to depression and anxiety, fatigue exerted a
      stronger effect on lung cancer survivors' HRQoL. Health professionals should
      consider the reduction of fatigue a priority in improving cancer patients' HRQoL
      following the completion of cancer treatment.

PMID- 28755493
TI  - Osteoinductive porous biphasic calcium phosphate ceramic as an alternative to
      autogenous bone grafting in the treatment of mandibular bone critical-size
      defects.
AB  - The bone-induction capacity of a porous biphasic calcium phosphate (pBCP) using
      heterotopic implantation in mouse (mHI-model) and its efficacy as substitute for
      autograft in mandibular critical-size defect in rabbit (rabMCSD-model) was
      investigated. In mHI-model, pBCP was implanted into the thigh muscles and bone
      formation was histomorphometrically and immunohistochemically evaluated. In
      rabMCSD-model, 13 mm bone defects were treated with pBCP or autograft and bone
      repair comparatively evaluated by radiographic and histomorphometric methods. In
      mHI-model, formed bone and immunolabeling for bone morphogenetic protein-2 and
      osteopontin were observed in 90% of pBCP implanted samples after 12 weeks. In
      rabMCSD-model neither statistically significant difference was found in newly
      formed bone between pBCP and autograft groups at 4 weeks (18.8 +/- 5.5% vs 27.1
      +/- 5.6%), 8 weeks (22.3 +/- 2.7% vs 26.2 +/- 5.1), and 12 weeks (19.6 +/- 4.7%
      vs 19.6 +/- 2.3%). At 12 weeks, the stability and contour of the mandible were
      restored in both treatments. Near tooth remaining, pBCP particles were covered by
      small amount of mineralized tissue exhibiting perpendicular attachments of
      collagen fiber bundles with histological characteristic of acellular cementum.
      Within the limitations of this study, it was concluded that pBCP is
      osteoinductive and able to stimulate the new formation of bone and cementum-like
      tissues in rabMCSD-model, suggesting that it may be an alternative to treatment
      of large bone defect and in periodontal regenerative therapy. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1546-1557,
      2018.

PMID- 28755494
TI  - Breastfeeding is associated with a decreased risk of childhood asthma
      exacerbations later in life.
AB  - BACKGROUND: Breastfeeding has been suggested to influence the risk of asthma and
      asthma severity in children. However, the conclusions from epidemiologic studies
      are inconsistent. METHODS: We used data from 960 children (aged 4-12 years) using
      regular asthma medication who participated in the PACMAN study. Breastfeeding
      exposure was based on questionnaire data and stratified into (i) ever vs never,
      and (ii) >=6 vs <6 months duration of breastfeeding. Asthma severity was based on
      the occurrence of asthma exacerbations in the preceding year and/or poorly
      controlled asthma symptoms during the last week of study visit. Odds ratios (ORs)
      were derived from univariate and multivariable logistic regression analyses.
      RESULTS: Breastfeeding was associated with a decreased risk of asthma
      exacerbations; adjusted (adj.) OR: 0.55 (95% confidence interval [CI]: 0.35
      0.87). After stratification for duration of breastfeeding, the adj. ORs were 0.48
      (95% CI: 0.27-0.84) for duration <6 months and 0.71 (95% CI: 0.43-1.20) for
      duration >=6 months breastfeeding. When we stratified the analysis by family
      history of asthma, the association between breastfeeding and asthma exacerbations
      was strong and statistically significant only in children with a positive family
      history of asthma; adj. OR: 0.34 (95% CI: 0.18-0.66). There was no association
      between breastfeeding and risk of poor asthma control; adj. OR: 1.04 (95% CI:
      0.76-1.41). CONCLUSION: In a pediatric population with asthma, children who had
      been breastfed had a statistically significantly lower risk of asthma
      exacerbations later in life compared to asthmatic children who had not been
      breastfed.

PMID- 28755495
TI  - Identification of good candidates for valgus bracing as a treatment for medial
      knee osteoarthritis.
AB  - : Valgus unloader braces are a conservative treatment option for medial
      compartment knee osteoarthritis that aim to unload the damaged medial compartment
      through application of an external abduction moment. Patient response to bracing
      is highly variable, however. While some experience improvements in pain,
      function, and joint loading, others receive little to no benefit. The objective
      of this work was to analyze clinical measures and biomechanical characteristics
      of unbraced walking to identify variables that are associated with the mechanical
      effectiveness of valgus unloader bracing. Seventeen patients with medial knee
      osteoarthritis walked overground with and without a valgus unloader brace. A
      musculoskeletal model was used to estimate the contact forces in the medial
      compartment of the tibiofemoral joint and brace effectiveness was defined as the
      decrease in peak medial contact force between unbraced and braced conditions.
      Stepwise linear regression was used to identify clinical and biomechanical
      measures that predicted brace effectiveness. The final regression model explained
      77% of the variance in brace effectiveness using two variables. Bracing was more
      effective for those with greater peak external hip adduction moments and for
      those with higher Kellgren-Lawrence grades, indicating more severe radiographic
      osteoarthritis. The hip adduction moment was the best predictor of brace
      effectiveness and was well correlated with several other measures indicating that
      it may be functioning as a "biomarker" for good bracing candidates. CLINICAL
      SIGNIFICANCE: The ability to predict good candidates for valgus bracing may
      improve issues of patient compliance and could enable the ability to train
      patients to respond better to bracing. (c) 2017 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 36:351-356, 2018.

PMID- 28755496
TI  - Procedure to select test organisms for environmental risk assessment of
      genetically modified crops in aquatic systems.
AB  - For a long time, the environmental risk assessment (ERA) of genetically modified
      (GM) crops focused mainly on terrestrial ecosystems. This changed when it was
      scientifically established that aquatic ecosystems are exposed to GM crop
      residues that may negatively affect aquatic species. To assist the risk
      assessment process, we present a tool to identify ecologically relevant species
      usable in tiered testing prior to authorization or for biological monitoring in
      the field. The tool is derived from a selection procedure for terrestrial
      ecosystems with substantial but necessary changes to adequately consider the
      differences in the type of ecosystems. By using available information from the
      Water Framework Directive (2000/60/EC), the procedure can draw upon existing
      biological data on aquatic systems. The proposed procedure for aquatic ecosystems
      was tested for the first time during an expert workshop in 2013, using the
      cultivation of Bacillus thuringiensis (Bt) maize as the GM crop and 1 stream type
      as the receiving environment in the model system. During this workshop, species
      executing important ecological functions in aquatic environments were identified
      in a stepwise procedure according to predefined ecological criteria. By doing so,
      we demonstrated that the procedure is practicable with regard to its goal: From
      the initial long list of 141 potentially exposed aquatic species, 7 species and 1
      genus were identified as the most suitable candidates for nontarget testing
      programs. Integr Environ Assess Manag 2017;13:974-979. (c) 2017 SETAC.

PMID- 28755497
TI  - Toward Improving Quality of End-of-Life Care: Encoding Clinical Guidelines and
      Standing Orders Using the Omaha System.
AB  - BACKGROUND: End-of-life care (EOLC) relieves the suffering of millions of people
      around the globe each year. A growing body of hospice care research has led to
      the creation of several evidence-based clinical guidelines for EOLC. As evidence
      for the effectiveness of timely EOLC swells, so does the increased need for
      efficient information exchange between disciplines and across the care continuum.
      AIMS: The purpose of this study was to investigate the feasibility of using the
      Omaha System as a framework for encoding interoperable evidence-based EOL
      interventions with specified temporality for use across disciplines and settings.
      METHODS: Four evidence-based clinical guidelines and one current set of hospice
      standing orders were encoded using the Omaha System Problem Classification Scheme
      and Intervention Scheme, as well as Systematized Nomenclature of Medicine
      Clinical Terms (SNOMED CT). The resulting encoded guideline was entered on a
      Microsoft Excel spreadsheet and made available for public use on the Omaha System
      Guidelines website. RESULTS: The resulting EOLC guideline consisted of 153
      interventions that may enable patients and their surrogates, clinicians, and
      ancillary providers to communicate interventions in a universally comprehensible
      way. LINKING EVIDENCE TO ACTION: Evidence-based interventions from diverse
      disciplines involved in EOLC are described within this guideline using the Omaha
      System. Because the Omaha System and clinical guidelines are maintained in the
      public domain, encoding interventions is achievable by anyone with access to the
      Internet and basic Excel skills. Using the guideline as a documentation template
      customized for unique patient needs, clinicians can quantify and track patient
      care across the care continuum to ensure timely evidence-based interventions.
      CONCLUSIONS: Clinical guidelines coded in the Omaha System can support the use of
      multidisciplinary evidence-based interventions to improve quality of EOLC across
      settings and professions.

PMID- 28755498
TI  - Effects of deltamethrin, dimethoate, and chlorpyrifos on survival and
      reproduction of the collembolan Folsomia candida and the predatory mite Hypoaspis
      aculeifer in two African and two European soils.
AB  - Indiscriminate use of pesticides is rampant in most parts of Africa, but only
      scanty ecotoxicological data exist for the protection of soil organisms-and these
      data were usually obtained under temperate conditions, including the use of
      Organisation for Economic Co-operation and Development (OECD) standard test
      protocols. In order to assess the effects of 3 commonly used pesticides
      (deltamethrin, dimethoate, chlorpyrifos) on soil fauna in Africa, noncontaminated
      natural soils were collected from Nigeria and Tunisia. In addition, 2 common test
      soils, OECD artificial soil and European (Landwirtschaftliche Untersichungs- und
      Forschungsanstalt [LUFA]) 2.3 soil, were used in OECD standard reproduction
      tests. Two microarthropod species, the springtail Folsomia candida and the
      predatory mite Hypoaspis aculeifer, were exposed in these 4 soils spiked
      individually with the 3 insecticides. Results show that the collembolan F.
      candida was more sensitive than the mite H. aculeifer for all 3 insecticides. The
      toxicity of each insecticide in the 4 soils differed, with few exceptions, by
      less than an order of magnitude. However, the pattern of toxicity was not
      consistent, that is, the lowest toxicity was often but not always found in OECD
      artificial soil. Soil- and pesticide-specific patterns of toxicity to F. candida
      and H. aculeifer might be related to the physicochemical properties of the soils
      and thus the availability of the 3 pesticides. Following the rules laid down in
      the European Union for the registration of pesticides and using standard European
      exposure scenarios, neither an acute nor a chronic risk of dimethoate and
      chlorpyrifos can be excluded (with few exceptions) in all 4 soils. Lower risks
      were identified for deltamethrin. For pesticide used in Africa, an environmental
      risk assessment based on data gained in tests with at least 1 additional natural
      field soil, preferably of African origin, should be performed using the same risk
      assessment principles as in the European Union. Integr Environ Assess Manag
      2018;14:92-104. (c) 2017 SETAC.

PMID- 28755499
TI  - Forecasting future recruitment success for Atlantic cod in the warming and
      acidifying Barents Sea.
AB  - Productivity of marine fish stocks is known to be affected by environmental and
      ecological drivers, and global climate change is anticipated to alter recruitment
      success of many stocks. While the direct effects of environmental drivers on fish
      early life stage survival can be quantified experimentally, indirect effects in
      marine ecosystems and the role of adaptation are still highly uncertain. We
      developed an integrative model for the effects of ocean warming and acidification
      on the early life stages of Atlantic cod in the Barents Sea, termed SCREI
      (Simulator of Cod Recruitment under Environmental Influences). Experimental
      results on temperature and CO2 effects on egg fertilization, egg and larval
      survival and development times are incorporated. Calibration using empirical time
      series of egg production, temperature, food and predator abundance reproduces age
      0 recruitment over three decades. We project trajectories of recruitment success
      under different scenarios and quantify confidence limits based on variation in
      experiments. A publicly accessible web version of the SCREI model can be run
      under www.oceanchange.uni-bremen.de/;SCREI. Severe reductions in average age-0
      recruitment success of Barents Sea cod are projected under uncompensated warming
      and acidification toward the middle to end of this century. Although high
      population stochasticity was found, considerable rates of evolutionary adaptation
      to acidification and shifts in organismal thermal windows would be needed to
      buffer impacts on recruitment. While increases in food availability may mitigate
      short-term impacts, an increase in egg production achieved by stock management
      could provide more long-term safety for cod recruitment success. The SCREI model
      provides a novel integration of multiple driver effects in different life stages
      and enables an estimation of uncertainty associated with interindividual and
      ecological variation. The model thus helps to advance toward an improved
      empirical foundation for quantifying climate change impacts on marine fish
      recruitment, relevant for ecosystem-based assessments of marine systems under
      climate change.

PMID- 28755500
TI  - Bidirectional reporter assay using HAL promoter and TOPFLASH improves specificity
      in high-throughput screening of Wnt inhibitors.
AB  - Constitutive activation of Wnt signaling plays an important role in colorectal
      and liver tumorigenesis. Cell-based assays using synthetic TCF/LEF (T-cell
      factor/lymphoid enhancer factor) reporters, as readouts of beta-catenin/TCF
      dependent transcriptional activity, have contributed greatly to the discovery of
      small molecules that modulate Wnt signaling. In the present study, we report a
      novel screening method, called a bidirectional dual reporter assay. Integrated
      transcriptome analysis identified a histidine ammonia-lyase gene (HAL) that was
      negatively regulated by beta-catenin/TCF-dependent transcriptional activity. We
      leveraged a promoter region of the HAL gene as another transcriptional readout of
      Wnt signaling. Cells stably expressing both an optimized HAL reporter and the
      TCF/LEF reporter enabled bidirectional reporter activities in response to Wnt
      signaling. Increased HAL reporter activity and decreased TCF/LEF reporter
      activity were observed simultaneously in the cells when beta-catenin/TCF7L2 was
      inhibited. Notably, this method could decrease the number of false positives
      observed when screening an inhibitor library compared with the conventional
      TCF/LEF assay. We found that Brefeldin A, a disruptor of the Golgi apparatus,
      inhibited the Wnt/beta-catenin signaling pathway. The utility of our system could
      be expanded to examine other disease-associated pathways beyond the Wnt/beta
      catenin signaling pathway.

PMID- 28755501
TI  - Promoter Choice Impacts the Efficiency of Plant Glyco-Engineering.
AB  - Glyco-modulation of therapeutic proteins produced in plants has shown great
      success. Plant-based expression platforms for tailored human-like N-glycosylation
      are based on the overexpression of foreign genes. However, drawbacks such as
      protein miss targeting, interference with endogenous glycosyltransferases, or
      with plant development hamper the widespread use of the technology. Here a
      technique that facilitates the generation of recombinant proteins with targeted N
      glycosylation at high homogeneity is described. It is focused on the synthesis of
      human-type beta1,4-galactosylation by the overexpression of the human beta1,4
      galactosyltransferase (GalT) in Nicotiana benthamiana. A GalT construct that
      targets the enzyme to the required late Golgi compartment (ST GalT) is
      transiently co-expressed with two pharmaceutically relevant glycoproteins. The
      impact of eight promoters driving the expression of ST GalT is evaluated by mass
      spectrometry (MS) -based analyses. It is shown that five promoters (amongst them
      high expressors) induce aberrant non-human glycosylation. In contrast, three
      promoters, considered as moderately active, regulate gene expression to levels
      leading to an improved efficiency of di-galactosylation (and subsequent
      sialylation) on the reporter proteins. The results point to the importance of
      promoter choice for optimizing glycan engineering processes.

PMID- 28755502
TI  - An Efficient Transformation Method for the Bioplastic-Producing "Knallgas"
      Bacterium Ralstonia eutropha H16.
AB  - Ralstonia eutropha H16 (also known as Cupriavidus necator H16) is a Gram-negative
      lithoautotrophic beta-proteobacterium with increasing biotechnological
      applications, including carbon capture and utilization, biopolymer synthesis, and
      biofuel production. Engineering of this organism is supported by the availability
      of its genome sequence and suitable plasmid systems. However, the lack of a
      simple and robust transformation method remains a challenge as it limits both the
      pace and ease of engineering this organism. To overcome this limitation, a
      systematic study is performed to evaluate the effects of different parameters on
      the transformation efficiency of R. eutropha H16. The optimized electroporation
      protocol uses R. eutropha H16 cells grown to OD600 0.6. These cells are made
      competent by a 15-min incubation in 50 mM CaCl2 , followed by two cell washes and
      final resuspension in 0.2 M sucrose prior to electroporation using 2.3 kV. This
      protocol achieves a transformation efficiency of (3.86 +/- 0.29) * 105  cfu ug-1
      DNA, a 103 -fold improvement compared to a previously published value for the
      same plasmid. This transformation method is a valuable tool for R. eutropha H16
      research and will further enable the development of other advanced molecular
      biology methods for this industrially relevant microorganism.

PMID- 28755503
TI  - Spectrum evaluation-assisted eicosanoid metabolomics for global eicosanoid
      profiling in human vascular endothelial cells.
AB  - Eicosanoids are hundreds of metabolites derived from poly-unsaturated fatty acids
      (PUFAs), which regulate biological processes from multiple angles via a complex
      metabolic network. Targeted eicosanoid metabolomics is used to study the
      eicosanoid profile in biological samples but only for eicosanoids with available
      standards. To expand the coverage of eicosanoids detected, we identified the
      eicosanoids without available standards by estimation of the retention time and
      comparison of the MS/MS spectra with the reference ones which was collected in a
      database from literature. Scheduled multiple reaction monitoring- information
      dependent acquisition- enhanced product ion (sMRM-IDA-EPI) scan mode was applied
      in this method, which was called Spectrum Evaluation-assisted Eicosanoid
      Metabolomics (SEEM). By using this method, 243 eicosanoids (167 without
      standards) could be relatively quantified with precision over 90 percent. We
      applied the method to analyze the global profile of eicosanoids secreted by human
      umbilical vascular endothelial cells at the basal level and with n-3 PUFA
      treatment. 26 putative eicosanoids showed altered levels, despite no available
      standards. In general, n-3 PUFA treatment increased most of their own metabolites
      and decreased the epoxy-, hydroxyl- and keto- linoleic acid metabolites. The
      application of the SEEM method proved its potency of identification and
      quantification of eicosanoids without standards.

PMID- 28755504
TI  - Multicomponent determination of traditional Chinese medicine preparation yin-zhi
      huang injection by LC-MS/MS for screening of its potential bioactive candidates
      using HepaRG cells.
AB  - Yin-zhi-huang (YZH) injection is an injectable multiherbal prescription derived
      from the ancient Chinese medicine formula of Yin-chen-hao-tang, which is widely
      used in the clinic for the treatment of jaundice and chronic liver diseases. To
      date, the systematic study of the components in this multiherbal prescription
      still lacks suitable analytical methods that are able to simultaneously detect a
      broad array of components at low concentrations. In this study, a new liquid
      chromatography-tandem mass spectrometry method using dynamic multiple reaction
      monitoring mode was developed to determine multiple peaks in traditional Chinese
      medicine preparation YZH injection. This simple, selective and sensitive method
      enabled the quantification of 22 components with standard materials with a lower
      limit of quantification of 1.46-12.5 ng/mL in cell lysates. This method was
      successfully applied to celluar uptake and binding investigation of components in
      YZH injection. The results indicated that this strategy might be a useful
      approach for rapidly screening of the potential bioactive candidates from YZH
      injection, and the discovered candidates could be used to investigate the
      pharmacodynamics in further studies.

PMID- 28755505
TI  - Risk of appendiceal endometriosis among women with deep-infiltrating
      endometriosis.
AB  - OBJECTIVE: To determine whether deep-infiltrating endometriosis (DE) carries an
      increased risk of appendiceal endometriosis (AppE) as compared with superficial
      endometriosis or no endometriosis. METHODS: In a retrospective study, data were
      obtained by chart review of an internal database for women who underwent
      coincidental appendectomy during benign gynecologic surgery between July 2009 and
      February 2014 at a tertiary referral center in the USA. Univariate, bivariate,
      and regression analyses were performed. The primary exposure was surgically
      documented endometriosis (DE, superficial, or no endometriosis). The primary
      outcome was AppE. RESULTS: Endometriosis was diagnosed for 151 (38.2%) of 395
      women; 82 (54.3%) had DE. The prevalence of AppE was 13.2% (52/395) overall; 8
      (11.6%) of 69 women with superficial endometriosis and 32 (39.0%) of 82 with DE
      were affected. Frequency of AppE was increased among women with DE, abnormal
      appendix appearance, and surgical indication (all P<0.001). Women with DE had a
      5.9-fold (95% confidence interval [CI] 2.9-11.9) higher risk of AppE compared
      with women without endometriosis, controlling for appendiceal appearance and
      surgical indication, and a 2.7-fold (95% CI 1.2-6.2) higher risk of AppE compared
      with those with superficial endometriosis. CONCLUSION: Women with DE have
      increased risk of AppE. Coincidental appendectomy should form part of complete
      endometriosis excision for these patients.

PMID- 28755506
TI  - Assessment of bacteria and archaea in metalworking fluids using massive parallel
      16S rRNA gene tag sequencing.
AB  - : Determination of the bacterial diversity in industry-based liquid in-use water
      miscible metalworking fluid (MWF) samples was targeted by massive parallel
      multiplex DNA sequencing, either directly or upon pretreatment with propidium
      monoazide (PMA) that allows differentiation between intact and physically damaged
      cells. As MWFs provide a suitable basis of life for micro-organisms, the majority
      is preserved by biocides. 'Bio-concept' fluids on the other hand are bactericide
      free, which intentionally leads to substantial bacterial populations. Samples
      from both fluid types were chosen: A median of 51 operational taxonomic units at
      genera level (OTUs) were detected per sample, but only 13 were present at or
      above 1.0% of the total population in any PMA-treated sample analysed. As both
      fluid types were mainly dominated by Pseudomonas spp., we resolved this genus on
      the species level and found the Pseudomonas oleovorans/pseudoalcaligenes group to
      predominate. We also looked for archaea and detected Methanobrevibacter spp.,
      albeit in <3% of all samples analysed. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Water-miscible metalworking fluids provide a suitable base of life for micro
      organisms, mainly bacteria and fungi. Earlier publications suggested that the
      diversity is rather low, but these studies were largely based on heterotrophic
      plate counts. This might have resulted in underestimation of population density
      and microbial diversity as some organisms might just refuse to grow. This study
      used high-throughput sequencing in the absence and presence of propidium
      monoazide to explore bacterial and archaeal presence in metalworking fluids. We
      established that diversity is low and bacterial populations are dominated by the
      genus Pseudomonas spp.

PMID- 28755507
TI  - Identification and characterization of the phosphatidic acid-binding A. thaliana
      phosphoprotein PLDrp1 that is regulated by PLDalpha1 in a stress-dependent
      manner.
AB  - Phospholipase D (PLD) and its cleavage product phosphatidic acid (PA) are crucial
      in plant stress-signalling. Although some targets of PLD and PA have been
      identified, the signalling pathway is still enigmatic. This study demonstrates
      that the phosphoprotein At5g39570, now called PLD-regulated protein1 (PLDrp1),
      from Arabidopsis thaliana is directly regulated by PLDalpha1. The protein PLDrp1
      can be divided into two regions with distinct properties. The conserved N
      terminal region specifically binds PA, while the repeat-rich C-terminal domain
      suggests interactions with RNAs. The expression of PLDrp1 depends on PLDalpha1
      and the plant water status. Water stress triggers a pldalpha1-like phenotype in
      PLDrp1 mutants and induces the expression of PLDrp1 in pldalpha1 mutants. The
      regulation of PLDrp1 by PLDalpha1 and environmental stressors contributes to the
      understanding of the complex PLD regulatory network and presents a new member of
      the PA-signalling chain in plants.

PMID- 28755508
TI  - Solid Renal Tumors Isoenhancing to Kidneys on Contrast-Enhanced Sonography:
      Differentiation From Pseudomasses.
AB  - OBJECTIVES: To estimate the prevalence of solid renal tumors isoenhancing to
      kidneys in all vascular phases on contrast-enhanced sonography and to investigate
      whether they can be differentiated from pseudomasses. METHODS: A computer search
      of the databases of 3 institutions identified 31 patients with pseudomasses and
      380 patients with solid tumors investigated with contrast-enhanced sonography.
      Nineteen of 380 (5%) patients had tumors isoenhancing in all phases. Images and
      clips of these 19 tumors and the 31 pseudomasses were blindly assessed by 2
      radiologists. They were asked to differentiate tumors from pseudomasses based on
      echogenicity, vascular architecture, and the presence of the medulla. RESULTS:
      Isoenhancing tumors were clear cell carcinomas (n = 7), angiomyolipomas (n = 3),
      papillary tumors (n = 3), metastasis (n = 1), and oncocytoma (n = 1). In the 4
      nonoperated tumors, the diagnosis was confirmed by progression during the follow
      up. There were 3 markedly hyperechoic, 11 mildly hypo/hyperechoic, and 5
      isoechoic masses. Most pseudomasses were isoechoic to kidneys (23 of 31), with
      the medulla identified in 22 of 31 and 15 of 31 by radiologists 1 and 2,
      respectively. One and 2 pseudomasses were considered tumors by radiologists 1 and
      2, respectively. One isoechoic isoenhancing tumor was not identified on contrast
      enhanced sonography. Isoenhancing tumors in all phases were differentiated from
      pseudomasses by combining grayscale and contrast-enhanced sonography (areas under
      the receiver operating characteristic curve, 0.997 for reader 1; 0.969 for reader
      2), with very good inter-reader agreement (weighted kappa = 0.81). CONCLUSIONS:
      In our retrospective study, 5% of solid renal lesions were isoenhancing to
      kidneys in all phases. Differentiation from pseudomasses was possible by looking
      at baseline sonographic features and vascular characteristics.

PMID- 28755509
TI  - The changes in, and relationship between, plasma nitric oxide and corticotropin
      releasing hormone in patients with major depressive disorder.
AB  - There is strong evidence of roles of the hypothalamus-pituitary-adrenal axis and
      nitric oxide (NO) synthase-NO system in depression, but the relationship between
      them is unknown. The aim of this study, therefore, was to elucidate whether there
      is any correlation between NO and corticotropin-releasing hormone (CRH) in major
      depressive disorder (MDD) patients. In 16 outpatients with MDD and 18 healthy
      controls, the plasma amino acids citrulline (Cit) and arginine (Arg) were
      determined by high-performance liquid chromatography, and CRH levels was measured
      by radioimmunoassay. The Cit/Arg ratio was calculated as an index of NO
      synthesis. Correlations between NO and CRH were examined with the Spearman test.
      Before treatment, no significant correlation was observed between the plasma NO
      level and CRH levels in MDD patients. The plasma NO levels were significantly
      higher in MDD patients. A significant correlation was found between NO levels and
      Hamilton Depression Rating Scale (HAMD) scores in MDD patients. The plasma CRH
      levels were significantly higher in MDD patients than in controls. After
      monotherapy for 2 months, the NO levels had dramatically declined but were also
      higher than those in the controls. This study is the first report of the absence
      of a significant correlation between plasma NO and CRH levels, although both
      levels are elevated in MDD patients. Furthermore, the strong links between the
      plasma NO levels and the HAMD scores, as well as the increased NO reduction after
      remission, suggest that NO plays a key role in depression and may be an indicator
      of therapeutic success.

PMID- 28755510
TI  - Raising awareness of Graves' orbitopathy with early warning cards.
AB  - BACKGROUND: Clinically significant Graves' orbitopathy (GO) develops in about 25%
      of those with Graves' disease (GD); most cases of GD in the UK are managed by
      endocrinologists. Despite this, patients report significant delays before a
      diagnosis of GO is made. Measures to increase awareness of the early signs of GO
      and establishing a fast-track referral pathway to specialist care should overcome
      these delays and potentially improve outcomes. AIMS: We aimed to determine
      whether issuing a "GO early warning card" to all GD patients raises awareness of
      GO and facilitates early diagnosis, what percentage of cards result in a
      telephone contact, the number of "false reports" from card carriers and patient
      perceptions of the cards. METHODS: We designed cards, detailing common GO
      symptoms and a telephone number for patients developing symptoms. Cards were
      distributed to 160 GD patients, without known GO, attending four endocrine
      clinics in the UK (December 2015-March 2016). We recorded telephone contacts over
      twelve months from when the last card was distributed and gathered patient
      feedback. RESULTS: The early warning cards were well received by patients in
      general. Over twelve months, ten telephone contacts from nine patients, all
      related to ocular symptoms, were received (6% of cards issued). Nine calls
      resulted in an additional clinic review (for eight patients), and four diagnoses
      of GO were made. CONCLUSIONS: This pilot study demonstrates that it is feasible
      to distribute GO early warning cards in clinic, and that they can be used to
      facilitate an early diagnosis of GO.

PMID- 28755511
TI  - Preoperative predictors of conversion as indicators of local inflammation in
      acute cholecystitis: strategies for future studies to develop quantitative
      predictors.
AB  - BACKGROUND: Observational studies have identified risk factors for conversion
      from laparoscopic to open cholecystectomy in acute cholecystitis. The aim of this
      study is to evaluate the reliability of these predictors and to identify sources
      of heterogeneity in the studies. METHODS: OVID was searched for papers published
      from 1995 to 2016. Studies with more than 100 patients were included. Risk
      factors for conversion were abstracted and categorized by statistical
      significance. RESULTS: Eleven studies were evaluated. Inflammation with
      difficulty in anatomic identification was the most common reason of conversion.
      Because of heterogeneity among studies a quantitative approach was not possible.
      Therefore, qualitative analysis using a heat map was performed along with
      investigation into sources of heterogeneity with the aim of creating a framework
      for future quantitative studies. Age, maleness, and white blood cell count were
      most commonly identified predictors of conversion. Sources of heterogeneity were
      criteria for diagnosis of acute cholecystitis, selection of patients for
      laparoscopic cholecystectomy, selection of variables and variations in their
      thresholds. CONCLUSIONS: In acute cholecystitis, inflammation is the most common
      reason for conversion. Age, maleness and white blood cell count are common
      predictors of conversion. Large scale prospective studies with minimal
      heterogeneity are needed to establish validity of these and other predictors.

PMID- 28755512
TI  - Power of Orbitrap-based LC-high resolution-MS/MS for comprehensive drug testing
      in urine with or without conjugate cleavage or using dried urine spots after on
      spot cleavage in comparison to established LC-MSn or GC-MS procedures.
AB  - Reliable, sensitive, and comprehensive urine screening procedures by gas
      chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass
      spectrometry (LC-MS) with low or high resolution (HR) are of high importance for
      drug testing, adherence monitoring, or detection of toxic compounds. Besides
      conventional urine sampling, dried urine spots are of increasing interest. In the
      present study, the power of LC-HR-MS/MS was investigated for comprehensive drug
      testing in urine with or without conjugate cleavage or using dried urine spots
      after on-spot cleavage in comparison to established LC-MSn or GC-MS procedures.
      Authentic human urine samples (n = 103) were split in 4 parts. One aliquot was
      prepared by precipitation (UP), one by UP with conjugate cleavage (UglucP), one
      spot on filter paper cards and prepared by on-spot cleavage followed by liquid
      extraction (DUSglucE), and one worked-up by acid hydrolysis, liquid-liquid
      extraction, and acetylation for GC-MS analysis. The 3 series of LC-HR-MS/MS
      results were compared among themselves, to corresponding published LC-MSn data,
      and to screening results obtained by conventional GC-MS. The reference libraries
      used for the 3 techniques contained over 4500 spectra of parent compounds and
      their metabolites. The number of all detected hits (770 drug intakes) was set to
      100%. The LC-HR-MS/MS approach detected 80% of the hits after UP, 89% after
      UglucP, and 77% after DUSglucE, which meant over one-third more hits in
      comparison to the corresponding published LC-MSn results with <=49% detected
      hits. The GC-MS approach identified 56% of all detected hits. In conclusion, LC
      HR-MS/MS provided the best screening results after conjugate cleavage and
      precipitation.

PMID- 28755513
TI  - Cytological features of the Warthin-like variant of salivary mucoepidermoid
      carcinoma.
AB  - Warthin-like mucoepidermoid carcinoma is a recently proposed variant of
      musoepidermoid carcinoma. Histologically, it is characterized by its close
      resemblance to Warthin tumor, including dense lymphocytic infiltration, flattened
      intermediate epithelium resembling squamous metaplasia, and cystic change. Given
      its histologic similarity to Warthin tumor, confirmatory testing for MAML2
      rearrangement is often required for this diagnosis. Here we present the first
      cytologic reports of two 53-year-old female patients with parotid masses. In both
      cases, the fine needle aspirations showed fragments of bland epithelium with a
      squamous appearance, mucinous cyst content, and focal lymphocytic background.
      Neither frank keratinization nor mucinous cells were identified in the smears.
      Fluorescence in situ hybridization (FISH) study confirmed MAML2 rearrangement on
      the resection specimens in both. Other cytologic differential diagnoses,
      including Warthin tumor with metaplasia, lymphadenoma, and lymphoepithelial cyst,
      were briefly discussed.

PMID- 28755514
TI  - Severe maternal morbidity and perinatal outcomes of multiple pregnancy in the
      Brazilian Network for the Surveillance of Severe Maternal Morbidity.
AB  - OBJECTIVE: To compare severe maternal complications (potentially life-threatening
      conditions [PLTCs], maternal near miss [MNM], and maternal death) and perinatal
      outcomes between multiple and singleton pregnancies. METHODS: A secondary
      analysis was undertaken using data from the Brazilian Network for Surveillance of
      Severe Maternal Morbidity (prospective surveillance of morbidities in 27
      Brazilian obstetric units between July 2009 and June 2010). Health indicators and
      criteria used for PLTCs and MNM were assessed. Adjusted prevalence ratios (PRadj
      ) with 95% confidence intervals (CIs) were calculated for perinatal outcomes.
      RESULTS: Among 267 multiple pregnancies, 235 (88.0%) were affected by PLTCs, 25
      (9.4%) by MNM, and 7 (2.6%) by maternal death; these prevalences did not differ
      from singleton pregnancies (n=7986). Management criteria for MNM were used almost
      twice as much in multiple pregnancies (PRadj 1.85, 95% CI 1.41-2.42). Preterm
      birth (PRadj 1.62, 95% CI 1.41-1.86), low birthweight (PRadj 1.73, 95% CI 1.45
      2.06 for the first-born vs singleton), any adverse perinatal outcome (PRadj 1.12,
      95% CI 1.03-1.22 for the second- vs first-born), and neonatal near miss (PRadj
      1.37, 95% CI 1.13-1.67 for the second-born vs singleton) were significantly
      associated with multiple pregnancy. CONCLUSION: Among cases of severe maternal
      morbidity, perinatal but not maternal outcomes were poorer for multiple
      pregnancies than for singletons. Differentiated care is needed during pregnancy
      and childbirth.

PMID- 28755515
TI  - Bufalin, a bufanolide steroid from the parotoid glands of the Chinese toad,
      suppresses hERG K+ currents expressed in HEK293 cells.
AB  - In this study, we investigated the effect of bufalin on the human ether-a-go-go
      related gene (hERG) K+ channels using the perforated patch recording technique.
      We measured a half-maximal inhibitory concentration (IC50 ) of 24.83 MUM and
      maximal inhibitory effect of 39.45 +/- 1.14% with bufalin. These findings suggest
      that bufalin is a potent hERG K+ channel blocker and may provide a new way for
      understanding Chan Su-induced arrhythmia.

PMID- 28755516
TI  - NOS1AP genetic variation is associated with impaired healing of diabetic foot
      ulcers and diminished response to healing of circulating stem/progenitor cells.
AB  - It is unclear why many with diabetes develop foot ulcers (DFU) and why some do
      not heal. It could be associated with genetic variation. We have previously shown
      that NOS1AP variation is associated with lower extremity amputation in those with
      diabetes and that circulating stem progenitor cell concentration (SPC) is
      associated with impaired foot ulcer healing in those with diabetes. The goal of
      this study was to determine if NOS1AP variation is associated with impaired wound
      healing and with SPC mobilization in those with DFU. In longitudinal cohort study
      we demonstrate that NOS1AP variants rs16849113 and rs19649113 are associated with
      impaired wound healing and with SPC mobilization in those with DFU. We believe
      that further study of NOS1AP is merited and that it NOS1AP might be associated
      with a functional impairment.

PMID- 28755517
TI  - Morphological features of congenital dyserythropoietic anemia type I: The role of
      electron microscopy in diagnosis.
AB  - INTRODUCTION: Congenital dyserythropoietic anemias are rare blood disorders
      characterized by congenital anemia and a wide range of morphological and
      functional abnormalities of erythroid precursors. OBJECTIVES: To analyze the
      relative frequency of both light microscopic (LM) and electron microscopic (EM)
      morphological features of erythroblasts in a large group of patients with
      molecular proven congenital dyserythropoietic anemia type I (CDAI). METHODS: We
      retrospectively evaluated the LM and EM of bone marrow (BM) erythroblasts in 35
      patients with CDAI. Thirty-four patients carried the CDAN1 Arg1042Trp founder
      mutation and one the p.Pro1130Leu mutation. BM slides of 24 patients were
      available for LM examination. EM studies were performed in all 35 patients.
      RESULTS: On LM, marked erythroid hyperplasia, binuclear erythroblasts, and
      various non-specific dyserythropoietic features were documented in every case;
      internuclear chromatin bridges were detected in 19 patients (79%). In all, EM of
      erythroblasts revealed a spongy appearance of heterochromatin, a widening of
      nuclear pores, and invagination of cytoplasm into the nuclear region.
      CONCLUSIONS: EM studies revealed high morphological frequency of specific
      ultrastructural changes in erythroblasts which facilitate prompt diagnosis of
      CDAI. Due to low specificity of BM LM findings, when BM EM is unavailable
      diagnostic approach should also include other inherited anemias.

PMID- 28755518
TI  - Hymen protection and the sexual practices, perceptions, and attitudes of female
      university students from Lebanon.
AB  - OBJECTIVE: To investigate associations between hymen protection and women's
      alternative sexual practices, perceptions, and attitudes. METHODS: A cross
      sectional online survey was administered among university students (aged 18-30
      years) in Lebanon between April 30 and August 31, 2012. The present analysis
      focused on female students who had engaged in oral/anal sex. RESULTS: Among 416
      included women, 163 (39.3%) reported anal/oral sex to protect their hymen. Women
      ever concerned with hymen protection were less likely to be non-Lebanese and not
      religious/spiritual, but more likely to report unwanted sexual activities, a
      relationship in which they felt things were moving too fast physically, and to
      feel guilty about sexual feelings (all P<0.01). They were two-to-three times more
      likely to agree that it is harder to refuse sex after the first time and that
      oral sex is not as big of a deal as sexual intercourse (both P<0.001). Concerned
      women who later engaged in vaginal sex (n=75) were less religious and more
      accepting of premarital sex than were those who continued to protect their hymen
      (n=88; all P<0.005). CONCLUSION: Women concerned about hymen-breaking engage in
      alternative sexual practices, yet experience pressure, guilt, worry, and
      indecisiveness regarding their sex-related decisions. The navigation of sexual
      decisions is a more vulnerable process for these women because of prevailing
      patriarchal values and discriminating gender norms in Lebanon.

PMID- 28755519
TI  - Hierarchical role for transcription factors and chromatin structure in genome
      organization along adipogenesis.
AB  - : The three dimensional folding of mammalian genomes is cell type specific and
      difficult to alter suggesting that it is an important component of gene
      regulation. However, given the multitude of chromatin-associating factors, the
      mechanisms driving the colocalization of active chromosomal domains and the role
      of this organization in regulating the transcription program in adipocytes are
      not clear. Analysis of genome-wide chromosomal associations revealed cell type
      specific spatial clustering of adipogenic genes in 3T3-L1 cells. Time course
      analysis demonstrated that the adipogenic 'hub', sampled by PPARgamma and Lpin1,
      undergoes orchestrated reorganization during adipogenesis. Coupling the dynamics
      of genome architecture with multiple chromatin datasets indicated that among all
      the transcription factors (TFs) tested, RXR is central to genome reorganization
      at the beginning of adipogenesis. Interestingly, at the end of differentiation,
      the adipogenic hub was shifted to an H3K27me3-repressive environment in
      conjunction with attenuation of gene transcription. We propose a stage-specific
      hierarchy for the activity of TFs contributing to the establishment of an
      adipogenic genome architecture that brings together the adipogenic genetic
      program. In addition, the repositioning of this network in a H3K27me3-rich
      environment at the end of differentiation may contribute to the stabilization of
      gene transcription levels and reduce the developmental plasticity of these
      specialized cells. DATABASE: All sequence data reported in this paper have been
      deposited at GEO (http://www.ncbi.nlm.nih.gov/geo/) (GSE92475).

PMID- 28755520
TI  - Genetic variation in IRF4 expression modulates growth characteristics, tyrosinase
      expression and interferon-gamma response in melanocytic cells.
AB  - A SNP within intron4 of the interferon regulatory factor4 (IRF4) gene,
      rs12203592*C/T, has been independently associated with pigmentation and age
      specific effects on naevus count in European-derived populations. We have
      characterized the cis-regulatory activity of this intronic region and using human
      foreskin-derived melanoblast strains, we have explored the correlation between
      IRF4 rs12203592 homozygous C/C and T/T genotypes with TYR enzyme activity,
      supporting its association with pigmentation traits. Further, higher IRF4 protein
      levels directed by the rs12203592*C allele were associated with increased basal
      proliferation but decreased cell viability following UVR, an etiological factor
      in melanoma development. Since UVR, and accompanying IFNgamma-mediated
      inflammatory response, is associated with melanomagenesis, we evaluated its
      effects in the context of IRF4 status. Manipulation of IRF4 levels followed by
      IFNgamma treatment revealed a subset of chemokines and immuno-evasive molecules
      that are sensitive to IRF4 expression level and genotype including CTLA4 and PD
      L1.

PMID- 28755522
TI  - High-performance variants of plant diacylglycerol acyltransferase 1 generated by
      directed evolution provide insights into structure function.
AB  - Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the acyl-CoA-dependent
      biosynthesis of triacylglycerol, the predominant component of seed oil. In some
      oil crops, including Brassica napus, the level of DGAT1 activity can have a
      substantial effect on triacylglycerol production. Structure-function insights
      into DGAT1, however, remain limited because of the lack of a three-dimensional
      detailed structure for this membrane-bound enzyme. In this study, the amino acid
      residues governing B. napus DGAT1 (BnaDGAT1) activity were investigated via
      directed evolution, targeted mutagenesis, in vitro enzymatic assay, topological
      analysis, and transient expression of cDNA encoding selected enzyme variants in
      Nicotiana benthamiana. Directed evolution revealed that numerous amino acid
      residues were associated with increased BnaDGAT1 activity, and 67% of these
      residues were conserved among plant DGAT1s. The identified amino acid residue
      substitution sites occur throughout the BnaDGAT1 polypeptide, with 89% of the
      substitutions located outside the putative substrate binding or active sites. In
      addition, cDNAs encoding variants I447F or L441P were transiently overexpressed
      in N. benthamiana leaves, resulting in 33.2 or 70.5% higher triacylglycerol
      content, respectively, compared with native BnaDGAT1. Overall, the results
      provide novel insights into amino acid residues underlying plant DGAT1 function
      and performance-enhanced BnaDGAT1 variants for increasing vegetable oil
      production.

PMID- 28755521
TI  - Antibiotic-induced dysbiosis of the microbiota impairs gut neuromuscular function
      in juvenile mice.
AB  - BACKGROUND AND PURPOSE: Gut microbiota is essential for the development of the
      gastrointestinal system, including the enteric nervous system (ENS).
      Perturbations of gut microbiota in early life have the potential to alter
      neurodevelopment leading to functional bowel disorders later in life. We examined
      the hypothesis that gut dysbiosis impairs the structural and functional integrity
      of the ENS, leading to gut dysmotility in juvenile mice. EXPERIMENTAL APPROACH:
      To induce gut dysbiosis, broad-spectrum antibiotics were administered by gavage
      to juvenile (3weeks old) male C57Bl/6 mice for 14 days. Bile acid composition in
      the intestinal lumen was analysed by liquid chromatography-mass spectrometry.
      Changes in intestinal motility were evaluated by stool frequency, transit of a
      fluorescent-labelled marker and isometric muscle responses of ileal full
      thickness preparations to receptor and non-receptor-mediated stimuli. Alterations
      in ENS integrity were assessed by immunohistochemistry and Western blot analysis.
      KEY RESULTS: Antibiotic treatment altered gastrointestinal transit, luminal bile
      acid metabolism and bowel architecture. Gut dysbiosis resulted in distorted glial
      network, loss of myenteric plexus neurons, altered cholinergic, tachykininergic
      and nitrergic neurotransmission associated with reduced number of nNOS neurons
      and different ileal distribution of the toll-like receptor TLR2. Functional
      defects were partly reversed by activation of TLR2 signalling. CONCLUSIONS AND
      IMPLICATIONS: Gut dysbiosis caused complex morpho-functional neuromuscular
      rearrangements, characterized by structural defects of the ENS and increased
      tachykininergic neurotransmission. Altogether, our findings support the
      beneficial role of enteric microbiota for ENS homeostasis instrumental in
      ensuring proper gut neuromuscular function during critical stages of development.

PMID- 28755523
TI  - Reactivity of the Sterically Demanding Siloxanediol Mes2 Si(OH)(MU-O)Si(OH)Mes2
      Towards Water and Ether Molecules.
AB  - A series of isotopologues of the siloxanediol Mes2 Si(OH)(MU-O)Si(OH)Mes2 (3 a)
      (Mes=2,4,6-trimethylphenyl) were synthesized by reactions of the corresponding
      disiloxane precursors Mes2 Si(MU-O)2 SiMes2 (2 a), Mes2 Si(MU-17 O)2 SiMes2 (2 b)
      or Mes2 Si(MU-18 O)2 SiMes2 (2 c) with an excess of H2 O, H217 O or H218 O. NMR
      and IR signal assignments for the siloxanediols in benzene are supported by
      quantum-chemical calculations, which indicate small energy differences between
      trans and cis conformers, the latter of which exhibits an intramolecular hydrogen
      bond. 1 H NMR as well as IR data suggest the presence of a mixture of both
      conformers in C6 D6 . Hydrogen-bonded adducts of Mes2 Si(OH)(MU-O)Si(OH)Mes2 with
      ethers such as diethylether, dimethoxyethane or dioxane were observed in the
      solid state, where they form polymeric chain-like structures. The latter appear
      to be stable only in the crystal. 17 O{1 H} NMR and IR data in THF solution
      suggest an interaction of 3 a with at least one THF molecule, whereas
      diethylether appears not to interact. Water adducts form neither in solution nor
      in the solid state as indicated by NMR and ATR IR data. 17 O{1 H} NMR and ESI-MS
      experiments illustrate the remarkably high stability of the siloxanediols towards
      water and show no evidence for intra- or intermolecular oxygen-exchange
      reactions. In marked contrast, a stepwise exchange of all three oxygen atoms
      including the one in the Si-O-Si bridge-occurred in the gas phase, when [Mes2
      Si(18 OH)(MU-18 O)Si(18 O)Mes2 ]- was treated with H2 O in the hexapole of an ESI
      FT-ICR mass spectrometer. The scrambling between the bridging and the other
      oxygen atoms likely proceeds through cyclic Si2 O2 intermediates.

PMID- 28755524
TI  - Structure of the Francisella response regulator QseB receiver domain, and
      characterization of QseB inhibition by antibiofilm 2-aminoimidazole-based
      compounds.
AB  - With antibiotic resistance increasing at alarming rates, targets for new
      antimicrobial therapies must be identified. A particularly promising target is
      the bacterial two-component system. Two-component systems allow bacteria to
      detect, evaluate and protect themselves against changes in the environment, such
      as exposure to antibiotics and also to trigger production of virulence factors.
      Drugs that target the response regulator portion of two-component systems
      represent a potent new approach so far unexploited. Here, we focus efforts on the
      highly virulent bacterium Francisella tularensis tularensis. Francisella contains
      only three response regulators, making it an ideal system to study. In this
      study, we initially present the structure of the N-terminal domain of QseB, the
      response regulator responsible for biofilm formation. Subsequently, using binding
      assays, computational docking and cellular studies, we show that QseB interacts
      with2-aminoimidazole based compounds that impede its function. This information
      will assist in tailoring compounds to act as adjuvants that will enhance the
      effect of antibiotics.

PMID- 28755525
TI  - A distinct serum metabolic signature of distant metastatic papillary thyroid
      carcinoma.
AB  - BACKGROUND: Although the incidence rate for thyroid cancer seems to have begun
      stabilizing in recent years, an increased rate of advanced stage of this disease
      has been reported. Additionally, distant metastasis is one of the most important
      prognostic factors of patients with papillary thyroid carcinoma (PTC).
      Unfortunately, the underlying mechanisms of distant metastasis, as well as cell
      status like metabolism changes in distant metastatic tumours have not been
      clearly elucidated. OBJECTIVE: To identify serum metabolic signature of distant
      metastatic PTC. DESIGN, PATIENTS AND MEASUREMENTS: In this study, gas
      chromatography-time-of-flight mass spectrometry (GC-TOF-MS) was used to analyse
      the serum from 77 patients diagnosed with PTC (37 in distant metastasis group and
      40 in ablation group). Principal component analysis (PCA) and orthogonal partial
      least-squares-discriminant analysis (OPLS-DA) scores plots were used to analyse
      the data. RESULTS: Principal component analysis and OPLS-DA analyses demonstrated
      an evident trend of separation between 40 serum samples from the ablation group
      and 37 samples from distant metastasis group. A total of 31 metabolites were
      identified, which are related to amino acid, lipid, glucose, vitamin metabolism
      and diet/gut microbiota interaction. Pathway analysis showed "alanine, aspartate
      and glutamate metabolism" and "inositol phosphate metabolism" were the most
      relevant pathways. CONCLUSION: Serum metabolomics profiling could significantly
      discriminate papillary thyroid cancer patients according to distant metastasis.
      Potential metabolic aberration in distant metastatic PTC could be involved in
      different biological behaviours of tumour cells including proliferation,
      invasion/migration and immune escape. Diet/gut microbiota-produced metabolites
      could play an important role in these effects. This work may provide new clues to
      find the underlying mechanisms regarding the distant metastasis of PTC as well as
      potential adjuvant therapy targets.

PMID- 28755526
TI  - Blood and nasal epigenetics correlate with allergic rhinitis symptom development
      in the environmental exposure unit.
AB  - BACKGROUND: Epigenetic alterations may represent new therapeutic targets and/or
      biomarkers of allergic rhinitis (AR). Our aim was to examine genome-wide
      epigenetic changes induced by controlled pollen exposure in the environmental
      exposure unit (EEU). METHODS: 38 AR sufferers and eight nonallergic controls were
      exposed to grass pollen for 3 hours on two consecutive days. We interrogated DNA
      methylation at baseline and 3 hours in peripheral blood mononuclear cells (PBMCs)
      using the Infinium Methylation 450K array. We corrected for demographics, cell
      composition, and multiple testing (Benjamini-Hochberg) and verified hits using
      bisulfite PCR pyrosequencing and qPCR. To extend these findings to a clinically
      relevant tissue, we investigated DNA methylation and gene expression of mucin 4
      (MUC4), in nasal brushings from a separate validation cohort exposed to birch
      pollen. RESULTS: In PBMCs of allergic rhinitis participants, 42 sites showed
      significant DNA methylation changes of 2% or greater. DNA methylation changes in
      tryptase gamma 1 (TPSG1), schlafen 12 (SLFN12), and MUC4 in response to exposure
      were validated by pyrosequencing. SLFN12 DNA methylation significantly correlated
      with symptoms (P < 0.05), and baseline DNA methylation pattern was found to be
      predictive of symptom severity upon grass allergen exposure (P = 0.029). Changes
      in MUC4 DNA methylation in nasal brushings in the validation cohort correlated
      with drop in peak nasal inspiratory flow (Spearman's r = 0.314, P = 0.034), and
      MUC4 gene expression was significantly increased (P < 0.0001). CONCLUSION: This
      study revealed novel and rapid epigenetic changes upon exposure in a controlled
      allergen challenge facility, and identified baseline epigenetic status as a
      predictor of symptom severity.

PMID- 28755527
TI  - Targeted dianthin is a powerful toxin to treat pancreatic carcinoma when applied
      in combination with the glycosylated triterpene SO1861.
AB  - Targeted cancer therapy provides the basis for the arrest of tumor growth in
      aggressive pancreatic carcinoma; however, a number of protein-based targeted
      toxins lack efficacy due to insufficient endosomal escape after being
      endocytosed. Therefore, we tested a fusion protein of the ribosome-inactivating
      protein dianthin and human epidermal growth factor in combination with a
      glycosylated triterpene (SO1861) that serves as an endosomal escape enhancer. In
      vitro investigations with the pancreatic carcinoma cell lines BxPC-3 and MIA PaCa
      2 revealed no significant differences to off-target cells in the half maximal
      inhibitory concentration (IC50 ) for the fusion protein. In contrast, combination
      with SO1861 decreased the IC50 for BxPC-3 cells from 100 to 0.17 nm, whereas
      control cells remained unaffected. Monotherapy of BxPC-3 xenografts in CD-1 nude
      mice led to a 51.7% average reduction in tumor size (40.8 mm3 ) when compared to
      placebo; however, combined treatment with SO1861 resulted in a more than 13-fold
      better efficacy (3.0 mm3 average tumor size) with complete regression in 80% of
      cases. Immunohistochemical analyses showed that tumor cells with lower target
      receptor expression are, in contrast to the combination therapy, able to escape
      from the monotherapy, which finally results in tumor growth. At the effective
      concentration, we did not observe liver toxicity and saw no other side effects
      with the exception of a reversible skin hardening at the SO1861 injection site,
      alongside an increase in platelet counts, plateletcrit, and platelet distribution
      width. In conclusion, combining a targeted toxin with SO1861 is proven to be a
      very promising approach for pancreatic cancer treatment.

PMID- 28755528
TI  - Tissue kallikrein-related peptidase 4 (KLK4), a novel biomarker in triple
      negative breast cancer.
AB  - Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors ER
      and PR and the oncoprotein HER2, is characterized by its aggressive pattern and
      insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related
      peptidases KLK1-15 provide a rich source of serine protease-type biomarkers
      associated with tumor growth and cancer progression for a variety of malignant
      diseases. In this study, recombinant KLK4 protein was generated and affinity
      purified KLK4-directed polyclonal antibody pAb587 established to allow
      localization of KLK4 protein expression in tumor cell lines and archived formalin
      fixed, paraffin-embedded TNBC tumor tissue specimens. For this, KLK4 protein
      expression was assessed by immunohistochemistry in primary tumor tissue sections
      (tissue microarrays) of 188 TNBC patients, mainly treated with anthracycline- or
      CMF-based polychemotherapy. KLK4 protein is localized in the cytoplasm of tumor
      and stroma cells. In this patient cohort, elevated stroma cell KLK4 expression,
      but not tumor cell KLK4 expression, is predictive for poor disease-free survival
      by univariate analysis (hazard ratio: 2.26, p=0.001) and multivariable analysis
      (hazard ratio: 2.12, p<0.01). Likewise, univariate analysis revealed a trend for
      statistical significance of elevated KLK4 stroma cell expression for overall
      survival of TNBC patients as well.

PMID- 28755529
TI  - PR3-anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis.

PMID- 28755530
TI  - Individual values of antineutrophil cytoplasmic antibodies do not correspond
      between antigen-specific assays.

PMID- 28755531
TI  - The role of ultrasound in the prediction of birth weight discordance in twin
      pregnancies: are we there yet?
AB  - OBJECTIVE: To analyze the accuracy of ultrasound prediction of birth weight
      discordance (BWD) and the influence of chorionicity and fetal growth restriction
      (FGR) on ultrasound performance. METHODS: Retrospective analysis of 176 twin
      pregnancies at a Portuguese tertiary center, between 2008 and 2014. Last
      ultrasound biometry was recorded. Cases with delivery before 24 weeks, fetal
      malformations, interval between last ultrasound and deliver >3 weeks, twin-to
      twin transfusion syndrome and monoamniotic pregnancies were excluded. The
      accuracy of prediction of BWD was assessed using the area under the receiver
      operating characteristics curve (AUC). RESULTS: BWD >=20% was present in 21.6% of
      twin pregnancies. EBW had the best predictive performance for BWD (AUC 0.838,
      95%CI 0.760-0.916), with a negative predictive value of 86.9% and a positive
      predictive value of 51.3%. Chorionicity did not influence ultrasound performance.
      None of the biometric variables analyzed was predictive of BWD in pregnancies
      without FGR. CONCLUSION: The accuracy of ultrasound in the prediction of BWD is
      limited, particularly in pregnancies without fetal growth restriction. Clinical
      decisions should not rely on BWD alone.

PMID- 28755532
TI  - Performance of Cardiac Magnetic Resonance Imaging for Diagnosis of Myocarditis
      Compared with Endomyocardial Biopsy: A Meta-Analysis.
AB  - BACKGROUND Cardiac magnetic resonance imaging (CMRI) is considered to be useful
      for the diagnosis of myocarditis, and the Lake Louise Criteria (LLC) has been
      proved to be of significance as the standard of diagnosis. However, the
      diagnostic performance of LLC-based CMRI for myocarditis compared with
      endomyocardial biopsy (EMB) has not been quantitatively evaluated in a meta
      analysis. MATERIAL AND METHODS The databases PubMed, Cochrane's Library, and
      EMBASE were searched to identify studies on LLC and its individual components for
      the diagnosis of myocarditis. EMB was the control reference. The sensitivity,
      specificity, and positive and negative diagnostic likelihood ratios were
      calculated with a random-effects model. The area under the receiver operating
      characteristic curve (AUC) was estimated to show overall effectiveness. RESULTS
      We included 9 cohorts (614 patients) of patients with suspected MC. The combined
      sensitivities, specificities, and AUCs for T1-weighed global relative enhancement
      were 0.66, 0.73, and 0.71; for T2-weighed edema ratio they were 0.52, 0.73, and
      0.72; for the late gadolinium enhancement, they were 0.70, 0.57, and 0.67; and
      for LLC-based CMRI they were 0.70, 0.56, and 0.70, respectively. Subgroup
      analysis indicated that the sensitivities, specificities, and diagnostic
      accuracies of LLC and its individual component-based CMRI seemed to be similar in
      patients with acute or chronic myocarditis. Results of the Deeks' funnel plot
      asymmetry test showed no significant publication bias among the studies.
      CONCLUSIONS CMRI based on LLC or its individual components seems to have moderate
      accuracy in diagnosis of acute or chronic myocarditis.

PMID- 28755533
TI  - Wasting away: How to treat cachexia and muscle wasting in chronic disease?

PMID- 28755534
TI  - Treadmill interventions in children under six years of age at risk of neuromotor
      delay.
AB  - BACKGROUND: Delayed motor development may occur in children with Down syndrome,
      cerebral palsy, general developmental delay or children born preterm. It limits
      the child's exploration of the environment and can hinder cognitive and social
      emotional development. Literature suggests that task-specific training, such as
      locomotor treadmill training, facilitates motor development. OBJECTIVES: To
      assess the effectiveness of treadmill interventions on locomotor development in
      children with delayed ambulation or in pre-ambulatory children (or both), who are
      under six years of age and who are at risk for neuromotor delay. SEARCH METHODS:
      In May 2017, we searched CENTRAL, MEDLINE, Embase, six other databases and a
      number of trials registers. We also searched the reference lists of relevant
      studies and systematic reviews. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) and quasi-RCTs that evaluated the effect of treadmill
      intervention in the target population. DATA COLLECTION AND ANALYSIS: Four authors
      independently extracted the data. Outcome parameters were structured according to
      the International Classification of Functioning, Disability and Health model.
      MAIN RESULTS: This is an update of a Cochrane review from 2011, which included
      five trials. This update includes seven studies on treadmill intervention in 175
      children: 104 were allocated to treadmill groups, and 71 were controls. The
      studies varied in population (children with Down syndrome, cerebral palsy,
      developmental delay or at moderate risk for neuromotor delay); comparison type
      (treadmill versus no treadmill; treadmill with versus without orthoses; high-
      versus low-intensity training); study duration, and assessed outcomes. Due to the
      diversity of the studies, only data from five studies were used in meta-analyses
      for five outcomes: age of independent walking onset, overall gross motor
      function, gross motor function related to standing and walking, and gait
      velocity. GRADE assessments of quality of the evidence ranged from high to very
      low.The effects of treadmill intervention on independent walking onset compared
      to no treadmill intervention was population dependent, but showed no overall
      effect (mean difference (MD) -2.08, 95% confidence intervals (CI) -5.38 to 1.22,
      2 studies, 58 children; moderate-quality evidence): 30 children with Down
      syndrome benefited from treadmill training (MD -4.00, 95% CI -6.96 to -1.04), but
      28 children at moderate risk of developmental delay did not (MD -0.60, 95% CI 
      2.34 to 1.14). We found no evidence regarding walking onset in two studies that
      compared treadmill intervention with and without orthotics in 17 children (MD
      0.10, 95% CI -5.96 to 6.16), and high- versus low-intensity treadmill
      interventions in 30 children with Down syndrome (MD -2.13, 95% -4.96 to
      0.70).Treadmill intervention did not improve overall gross motor function (MD
      0.88, 95% CI -4.54 to 6.30, 2 studies, 36 children; moderate-quality evidence) or
      gross motor skills related to standing (MD 5.41, 95% CI -1.64 to 12.43, 2
      studies, 32 children; low-quality evidence), and had a negligible improvement in
      gross motor skills related to walking (MD 4.51, 95% CI 0.29 to 8.73, 2 studies,
      32 children; low-quality evidence). It led to improved walking skills in 20
      ambulatory children with developmental delay (MD 7.60, 95% CI 0.88 to 14.32, 1
      study) and favourable gross motor skills in 12 children with cerebral palsy (MD
      8.00, 95% CI 3.18 to 12.82). A study which compared treadmill intervention with
      and without orthotics in 17 children with Down syndrome suggested that adding
      orthotics might hinder overall gross motor progress (MD -8.40, 95% CI -14.55 to 
      2.25).Overall, treadmill intervention showed a very small increase in walking
      speed compared to no treadmill intervention (MD 0.23, 95% CI 0.08 to 0.37, 2
      studies, 32 children; high-quality evidence). Treadmill intervention increased
      walking speed in 20 ambulatory children with developmental delay (MD 0.25, 95% CI
      0.08 to 0.42), but not in 12 children with cerebral palsy (MD 0.18, 95% CI -0.09
      to 0.45). AUTHORS' CONCLUSIONS: This update of the review from 2011 provides
      additional evidence of the efficacy of treadmill intervention for certain groups
      of children up to six years of age, but power to find significant results still
      remains limited. The current findings indicate that treadmill intervention may
      accelerate the development of independent walking in children with Down syndrome
      and may accelerate motor skill attainment in children with cerebral palsy and
      general developmental delay. Future research should first confirm these findings
      with larger and better designed studies, especially for infants with cerebral
      palsy and developmental delay. Once efficacy is established, research should
      examine the optimal dosage of treadmill intervention in these populations.

PMID- 28755535
TI  - Autistic traits and internet gaming addiction in Chinese children: The mediating
      effect of emotion regulation and school connectedness.
AB  - This report details an 18-month longitudinal study designed to investigate the
      influence of autistic traits' on internet gaming addiction (IGA) in children. A
      total of 420 Chinese children (220 boys, Mean age=9.74+/-0.45) participated in
      the research. Autistic traits were measured in the 4th grade and emotion
      regulation, school connectedness and IGA measured in both the 4th and 5th grades.
      After controlling for age, sex, and sensation seeking, results showed that
      autistic traits were related to decreased emotion regulation, which in turn was
      related to lower school connectedness, which was related to increased IGA. The
      results suggest that improving emotion regulation and school connectedness could
      reduce the risk of IGA. As a result, these findings may inform intervention and
      prevention programs targeting children with IGA, especially among those with high
      levels of autistic traits.

PMID- 28755536
TI  - Using fixed-parameter and random-parameter ordered regression models to identify
      significant factors that affect the severity of drivers' injuries in vehicle
      train collisions.
AB  - This study attempts to identify significant factors that affect the severity of
      drivers' injuries when colliding with trains at railroad-grade crossings by
      analyzing the individual-specific heterogeneity related to those factors over a
      period of 15 years. Both fixed-parameter and random-parameter ordered regression
      models were used to analyze records of all vehicle-train collisions that occurred
      in the United States from January 1, 2001 to December 31, 2015. For fixed
      parameter ordered models, both probit and negative log-log link functions were
      used. The latter function accounts for the fact that lower injury severity levels
      are more probable than higher ones. Separate models were developed for heavy and
      light-duty vehicles. Higher train and vehicle speeds, female, and young drivers
      (below the age of 21 years) were found to be consistently associated with higher
      severity of drivers' injuries for both heavy and light-duty vehicles.
      Furthermore, favorable weather, light-duty trucks (including pickup trucks, panel
      trucks, mini-vans, vans, and sports-utility vehicles), and senior drivers (above
      the age of 65 years) were found be consistently associated with higher severity
      of drivers' injuries for light-duty vehicles only. All other factors (e.g. air
      temperature, the type of warning devices, darkness conditions, and highway
      pavement type) were found to be temporally unstable, which may explain the
      conflicting findings of previous studies related to those factors.

PMID- 28755538
TI  - How "ought" exceeds but implies "can": Description and encouragement in moral
      judgment.
AB  - This paper tests a theory about the relationship between two important topics in
      moral philosophy and psychology. One topic is the function of normative language,
      specifically claims that one "ought" to do something. Do these claims function to
      describe moral responsibilities, encourage specific behavior, or both? The other
      topic is the relationship between saying that one "ought" to do something and
      one's ability to do it. In what respect, if any, does what one "ought" to do
      exceed what one "can" do? The theory tested here has two parts: (1) "ought"
      claims function to both describe responsibilities and encourage people to fulfill
      them (the dual-function hypothesis); (2) the two functions relate differently to
      ability, because the encouragement function is limited by the person's ability,
      but the descriptive function is not (the interaction hypothesis). If this theory
      is correct, then in one respect "ought implies can" is false because people have
      responsibilities that exceed their abilities. But in another respect "ought
      implies can" is legitimate because it is not worthwhile to encourage people to do
      things that exceed their ability. Results from two behavioral experiments support
      the theory that "ought" exceeds but implies "can." Results from a third
      experiment provide further evidence regarding an "ought" claim's primary function
      and how contextual features can affect the interpretation of its functions.

PMID- 28755537
TI  - Gender has to be taken into account in diagnosing adult growth hormone deficiency
      by the GHRH plus arginine test.
AB  - OBJECTIVE: Data on the effect of gender on the interpretation of the GHRH plus
      arginine stimulation test (GHRH+ARG test) is controversial. We validated the
      GHRH+ARG stimulation test in control subjects and patients with organic or
      idiopathic pituitary disease and a suspicion of adult growth hormone deficiency
      (AGHD) using the Immulite 2000 XPi GH assay. DESIGN: We studied 126 apparently
      healthy adults (median age 38.8years) and 34 patients with a suspicion of AGHD
      (median age 42.2years). Identification of AGHD with the GHRH+ARG test was
      investigated with commonly accepted BMI-related consensus cut-off limits for peak
      GH concentrations. Serum samples collected during the GHRH+ARG test were analysed
      for GH in 2014-2015. Serum IGF-1 concentrations were studied as a reference.
      RESULTS: In 14 of 65 (22%) control males the GH peak value was below the BMI
      related cut-off limits for GH sufficiency indicating a false diagnosis of AGHD.
      All control females had a normal GHRH+ARG response. Median peak GH response was
      significantly (p<0.001) higher in female (39.3MUg/L) than in male controls
      (21MUg/L). According to consensus cut-offs all but one young female patient had a
      deficient response compatible with a diagnosis of AGHD. CONCLUSIONS: The GH
      response to stimulation by GHRH+ARG is gender-dependent, being lower in healthy
      males than in females. Gender should be considered when defining cut-off limits
      for peak GH concentrations in the GHRH+ARG test. The presently used BMI-related
      cut-off levels will lead to a significant misclassification of males as GH
      deficient.

PMID- 28755539
TI  - Simultaneous inhibition of growth and metastasis of hepatocellular carcinoma by
      co-delivery of ursolic acid and sorafenib using lactobionic acid modified and pH
      sensitive chitosan-conjugated mesoporous silica nanocomplex.
AB  - Co-delivery multiple drugs using nanocarriers has been recognized as a promising
      strategy for cancer treatment to enhance therapeutic efficacy. In this study, a
      pH sensitive mesoporous silica nanoparticles (MSN) based controlled release
      nanoparticles for co-delivery of sorafenib (SO), a multi-tyrosine kinase
      inhibitor, and ursolic acid (UA), a sensitive agent for SO, was developed, which
      was decorated with pH sensitive chitosan (CS) and lactobionic acid (LA) targeting
      to asialoglycoprotein receptor (ASGPR) over-expressing hepatocellar carcinoma
      cells (denoted as USMNs-CL). The nanocomplex enhanced bioavailability of
      hydrophobic drugs, efficient tumor cell targeting and exhibited pH-responsive
      function and sustained release profile. USMNs-CL showed synergistic cytotoxicity
      and could attenuate the adhesion, migration of ASGPR over-expressing liver cancer
      SMMC-7721 cells at non-toxic concentrations. Moreover, the complex nanoparticles
      significantly increased the cellular apoptosis and down-regulated the expression
      of EGFR and VEGFR2 proteins related with cell proliferation and tumor
      angiogenesis. In vivo, compared with UA or SO alone, the nanocomplex
      significantly reduced the tumor burden in hepatocellular carcinoma (HCC) H22
      tumor-bearing mice model and inhibited the lung metastasis in the H22 lung
      metastasis models. Overall, co-delivery of UA and SO by MSN-CS-LA nanocarriers
      could provide a promising strategy for HCC combinational therapy, especially for
      the HCC metastasis chemoprevention.

PMID- 28755540
TI  - Adolescents, alcohol, and marijuana: Context characteristics and problems
      associated with simultaneous use.
AB  - We investigated contexts of simultaneous use of alcohol and marijuana and the
      impact of simultaneous use on problems among adolescents. Ecological momentary
      assessment data were obtained over two weekends from 150 adolescents in
      California (47% female, M age=16.36years), using smartphone surveys administered
      early and late in the evening and again the following morning. We assessed
      whether, in what context, and with whom adolescents drank alcohol and used other
      substances over 3 evening hours. We assessed problems they experienced each
      evening on the following morning. Results showed that greater adult supervision
      in every context was associated with a 55% lower risk of simultaneous use
      (RRR=0.45, p<=.05). Contexts with no other underage drinkers were associated with
      99% lower risk of simultaneous use (RRR=0.01, p<=.005). Each occasion of
      simultaneous use was related to 110% increase in the number of problems
      (IRR=2.10, p<=.005), with 83%, 221% and 311% greater odds of violence (OR=1.83,
      p<=.05), driving under the influence or riding with a drunk driver (OR=3.21,
      p<=.05), or being drunk (OR=4.11, p<=.005). Additional analyses showed that these
      problems may be attributed largely to the alcohol consumed in each context.
      Results demonstrate that it is essential to consider situational and social
      characteristics of substance use contexts to better understand adolescent
      simultaneous use of alcohol and drugs and problems.

PMID- 28755541
TI  - Vaccines targeting helper T cells for cancer immunotherapy.
AB  - There are compelling arguments for designing cancer vaccines specifically to
      induce CD4+ helper T cell responses. Recent studies highlight the crucial role of
      proliferating, activated effector memory Th1 CD4+ T cells in effective antitumor
      immunity and reveal that CD4+ T cells induce more durable immune-mediated tumor
      control than CD8+ T cells. CD4+ T cells promote antitumor immunity by numerous
      mechanisms including enhancing antigen presentation, co-stimulation, T cell
      homing, T cell activation, and effector function. These effects are mediated at
      sites of T cell priming and at the tumor microenvironment. Several cancer vaccine
      approaches induce durable CD4+ T cell responses and have promising clinical
      activity. Future work should further optimize vaccine adjuvants and combination
      therapies incorporating helper peptide vaccines.

PMID- 28755542
TI  - Towards an evidence based approach for the development of adjuvanted vaccines.
AB  - In the last two decades, several vaccines formulated with a new generation of
      adjuvants have been licensed or approved to target diseases such as influenza,
      hepatitis B, cervical cancer, and malaria. These new generation adjuvants appear
      to work by delivering a localized activation signal to the innate immune system,
      which in turn promotes antigen-specific adaptive immunity. Advances in
      understanding of the innate immune system together with high-throughput discovery
      of synthetic immune potentiators are now expanding the portfolio of new
      generation adjuvants available for evaluation. Meanwhile, omics and systems
      biology are providing molecular benchmarks or signatures to assess vaccine safety
      and effectiveness. This accumulating knowledge and experience raises the prospect
      that the future selection of the right antigen/adjuvant combination can be more
      evidence based and can speed up the clinical development program for new
      adjuvanted vaccines.

PMID- 28755543
TI  - Assessing income redistributive effect of health financing in Zambia.
AB  - Ensuring an equitable health financing system is a major concern particularly in
      many developing countries. Internationally, there is a strong debate to move away
      from excessive reliance on direct out-of-pocket (OOP) spending towards a system
      that incorporates a greater element of risk pooling and thus affords greater
      protection for the poor. This is a major focus of the move towards universal
      health coverage (UHC). Currently, Zambia with high levels of poverty and income
      inequality is implementing health sector reforms for UHC through a social health
      insurance scheme. However, the way to identify the health financing mechanisms
      that are best suited to achieving this goal is to conduct empirical analysis and
      consider international evidence on funding universal health systems. This study
      assesses, for the first time, the progressivity of health financing and how it
      impacts on income inequality in Zambia. Three broad health financing mechanisms
      (general tax, a health levy and OOP spending) were considered. Data come from the
      2010 nationally representative Zambian Living Conditions and Monitoring Survey
      with a sample size of 19,397 households. Applying standard methodologies, the
      findings show that total health financing in Zambia is progressive. It also leads
      to a statistically significant reduction in income inequality (i.e. a pro-poor
      redistributive effect estimated at 0.0110 (p < 0.01)). Similar significant pro
      poor redistribution was reported for general taxes (0.0101 (p < 0.01)) and a
      health levy (0.0002 (p < 0.01)). However, the redistributive effect was not
      significant for OOP spending (0.0006). These results further imply that health
      financing redistributes income from the rich to the poor with a greater potential
      via general taxes. This points to areas where government policy may focus in
      attempting to reduce the high level of income inequality and to improve equity in
      health financing towards UHC in Zambia.

PMID- 28755544
TI  - Highly efficient removal of trace thallium from contaminated source waters with
      ferrate: Role of in situ formed ferric nanoparticle.
AB  - Thallium (Tl) is highly toxic to mammals and relevant pollution cases are
      increasing world-widely. Convenient and efficient method for the removal of trace
      Tl from contaminated source water is imperative. Here, the removal of trace Tl by
      K2FeO4 [Fe(VI)] was investigated for the first time, with the exploration of
      reaction mechanisms. Six different types of water treatment agents (powdered
      activated carbon, Al2(SO4)3, FeCl3, delta-MnO2, MnO2 nano-particles, and K2FeO4)
      were used for the removal of Tl in spiked river water, and K2FeO4 showed
      excellent removal performance. Over 92% of Tl (1 MUg/L) was removed within 5 min
      by applying 2.5 mg/L of K2FeO4 (pH 7.0, 20  degrees C). XPS analysis revealed
      that in the reaction of Tl(I) with K2FeO4, Tl(I) was oxidized to Tl(III), and
      removed by the K2FeO4 reduced ferric particles. The removal of Tl by in situ
      formed and ex situ formed ferric particle was examined respectively, and the
      results revealed that the removal of trace Tl could be attributed to the
      combination of adsorption and coprecipitation processes. The hydrodynamic size of
      the reduced particle from K2FeO4 ranged from 10 nm to 100 nm, and its surface was
      negatively charged under neutral pH condition. These factors were conducive for
      the efficient removal of Tl by K2FeO4. The effects of solution pH, coexisting
      ions (Na+, Ca2+, and HCO3-), humic acid, solution temperature, and reductive
      environment on the removal and desorption of Tl were investigated, and the
      elimination of Tl in polluted river water and reservoir water was performed.
      These results suggest that K2FeO4 could be an efficient and convenient agent on
      trace Tl removal.

PMID- 28755545
TI  - Stereo-electroencephalography identifies N2 sleep and spindles in human
      hippocampus.
AB  - OBJECTIVES: To describe the hippocampal stereo-electroencephalogram during sleep
      according to sleep stages (including N2 sleep) and cycles, together with the
      hippocampal spindles. METHODS: All patients with drug-resistant focal epilepsy
      undergoing intra-hippocampal implantation between August 2012 and June 2013 at
      Nancy University Hospital were screened. Six patients with explored hippocampus
      devoid of pathological features were analyzed. During one night, we identified
      continuous periods of successive N2, N3 and REM sleep for two full cycles. We
      performed a spectral analysis of the hippocampal signal for each labeled sleep
      period. RESULTS: N2, N3 and REM sleeps were individualized according to their
      spectral powers, for each frequency band and sleep cycle. Hippocampal spindles
      showed dynamic intrinsic properties, the 11.5-16Hz frequency band being mainly
      dominant, whereas the 9-11.5Hz frequency band heightening during the beginning
      and the end of the transient. For N3 and REM sleep stages, the power of the
      hippocampal signal was significantly decreased between the first and the second
      sleep cycle. CONCLUSION: Distinct N2 sleep, fast spindles and homeostatic profile
      are all common properties shared by hippocampus and cortex during sleep.
      SIGNIFICANCE: The close functional link between hippocampus and cortex may have
      various sleep-related substrates.

PMID- 28755546
TI  - Temporal-spatial characteristics of phase-amplitude coupling in
      electrocorticogram for human temporal lobe epilepsy.
AB  - OBJECTIVE: Neural activity of the epileptic human brain contains low- and high
      frequency oscillations in different frequency bands, some of which have been used
      as reliable biomarkers of the epileptogenic brain areas. However, the
      relationship between the low- and high-frequency oscillations in different
      cortical areas during the period from pre-seizure to post-seizure has not been
      completely clarified. METHODS: We recorded electrocorticogram data from the
      temporal lobe and hippocampus of seven patients with temporal lobe epilepsy. The
      modulation index based on the Kullback-Leibler distance and the phase-amplitude
      coupling co-modulogram were adopted to quantify the coupling strength between the
      phase of low-frequency oscillations (0.2-10Hz) and the amplitude of high
      frequency oscillations (11-400Hz) in different seizure epochs. The time-varying
      phase-amplitude modulogram was used to analyze the phase-amplitude coupling
      pattern during the entire period from pre-seizure to post-seizure in both the
      left and right temporal lobe and hippocampus. Channels with strong modulation
      index were compared with the seizure onset channels identified by the
      neurosurgeons and the resection channels in the clinical surgery. RESULTS: The
      phase-amplitude coupling strength (modulation index) increased significantly in
      the mid-seizure epoch and decrease significantly in seizure termination and post
      seizure epochs (p<0.001). The strong phase-amplitude-modulating low- and high
      frequency oscillations in the mid-seizure epoch were mainly delta, theta, and
      alpha oscillations and gamma and ripple oscillations, respectively. The phase
      amplitude modulation and strength varied among channels and was asymmetrical in
      the left and right temporal cortex and hippocampus. The "fall-max" phase
      amplitude modulation pattern, i.e., high-frequency amplitudes were largest in the
      low-frequency phase range [-pi, 0], which corresponded to the falling edges of
      low-frequency oscillations, appeared in the middle period of the seizures at
      epileptic focus channels. Channels with strong modulation index appeared on the
      corresponding left or right temporal cortex of surgical resection and overlapped
      with the clinical resection zones in all patients. CONCLUSIONS: The "fall-max"
      pattern between the phase of low-frequency oscillation and amplitude of high
      frequency oscillation that appeared in the middle period of the seizures is a
      reliable biomarker in epileptogenic cortical areas. The modulation index can be
      used as a good tool for lateralization and localization for the epileptic focus
      in patients with epilepsy. SIGNIFICANCE: Phase-amplitude coupling can provide
      meaningful reference for accurate resection of epileptogenic focus and provide
      insight into the underlying neural dynamics of the epileptic seizure in patients
      with temporal lobe epilepsy.

PMID- 28755547
TI  - Tagging fast neutrons from a 252Cf fission-fragment source.
AB  - Coincidence and time-of-flight measurement techniques are employed to tag fission
      neutrons emitted from a 252Cf source sealed on one side with a very thin layer of
      Au. The source is positioned within a gaseous 4He scintillator detector. Together
      with alpha particles, both light and heavy fission fragments pass through the
      thin layer of Au and are detected. The fragments enable the corresponding fission
      neutrons, which are detected in a NE-213 liquid-scintillator detector, to be
      tagged. The resulting continuous polychromatic beam of tagged neutrons has an
      energy dependence that agrees qualitatively with expectations. We anticipate that
      this technique will provide a cost-effective means for the characterization of
      neutron-detector efficiency in the energy range 1-6MeV.

PMID- 28755548
TI  - Neutron activation and prompt gamma intensity in Ar/CO2-filled neutron detectors
      at the European Spallation Source.
AB  - Monte Carlo simulations using MCNP6.1 were performed to study the effect of
      neutron activation in Ar/CO2 neutron detector counting gas. A general MCNP model
      was built and validated with simple analytical calculations. Simulations and
      calculations agree that only the 40Ar activation can have a considerable effect.
      It was shown that neither the prompt gamma intensity from the 40Ar neutron
      capture nor the produced 41Ar activity have an impact in terms of gamma dose rate
      around the detector and background level.

PMID- 28755549
TI  - Childhood maltreatment is associated with increased risk of subclinical
      hypothyroidism in pregnancy.
AB  - The critical importance of thyroid hormones for fetal development is well
      established. The developing fetus is dependent on the mother for adequate thyroid
      hormone supply, and maternal thyroid dysfunction in pregnancy may result in
      suboptimal fetal development. Because exposure to childhood maltreatment (CM) has
      been associated with thyroid dysfunction in the non-pregnant state, we sought to
      test the hypothesis that exposure to CM may represent a risk factor for the
      development of maternal hypothyroidism in pregnancy. The study was conducted in a
      healthy cohort of 102 pregnant mothers who were followed across the entire course
      of pregnancy. At each trimester thyroid-stimulating hormone (TSH) and free
      thyroxine (fT4) were measured in maternal serum. Experience of CM was assessed
      using the Childhood Trauma Questionnaire. After adjusting for potentially
      confounding variables, CM exposure was associated with increased TSH
      concentrations across pregnancy (F1,94.6=11.52, p=0.001) and with a 4- to 7-fold
      increased risk of TSH levels above the trimester-specific clinical cut-off
      values. Women with clinically elevated TSH concentrations did not differ in fT4
      concentrations from women with normal TSH concentrations (p>0.1), suggesting
      subclinical hypothyroidism. Our findings suggest that there is a substantial and
      clinically relevant increased risk for thyroid dysfunction during pregnancy among
      women exposed to abuse or neglect in their childhood. This could potentially have
      adverse consequences for fetal brain development. Thus, these findings highlight
      the critical importance of considering CM exposure as a potential risk factor for
      (subclinical) hypothyroidism in pregnancy.

PMID- 28755550
TI  - Impact of early life adversity and tryptophan depletion on functional
      connectivity in menopausal women: A double-blind, placebo-controlled crossover
      study.
AB  - During the menopause transition, women are at increased risk of subjective
      symptoms of executive dysfunction. Evidence from animal and human participant
      studies suggests adverse childhood experiences (ACE) may be a risk factor for
      executive complaints during this hormonal transition. Preclinical literature
      indicates early life adversity effects on serotonin function may play a role in
      this increased susceptibility. However, the mechanisms underlying this increase
      in vulnerability in human participants remain relatively unknown. Here we
      examined the impact of ACE and tryptophan depletion (TD), a paradigm used to
      lower central serotonin levels, on functional network connectivity in discovery
      and replication datasets. We hypothesized that ACE would be associated with
      decreased within-network connectivity. We predicted that TD would further lower
      connectivity in women with high levels of early adversity, but have no effect in
      women with low levels of early adversity. Forty women underwent two functional
      imaging sequences at two time points (141 total scans) in a double-blind, placebo
      controlled, crossover study. The effects of ACE and TD were evaluated using
      generalized estimating equations (GEE). As predicted, ACE was associated with
      lower within-network connectivity. While TD had no effect on connectivity in the
      low ACE group, TD increased connectivity in the high ACE group. The robust effect
      of ACE remained significant in the replication dataset, though the ACE*TD
      interaction did not. Together, these results suggest that early life adversity
      has lasting impacts on large-scale functional networks underlying executive
      function. Alterations in functional network connectivity may be one mechanism by
      which early life adversity increases the risk of cognitive disorders during
      menopause.

PMID- 28755551
TI  - Natural magnetic pyrrhotite as a high-Efficient persulfate activator for
      micropollutants degradation: Radicals identification and toxicity evaluation.
AB  - This study discusses the SO4- based process mediated by natural magnetic
      pyrrhotite (NP) for the degradation of refractory organic micropollutants.
      Complete degradation of 20MUM phenol in distilled water (DW) was obtained within
      20min using NP/PS (persulfate) system. Electron paramagnetic resonance spectra
      indicated aerobic and acidic conditions favored the generation of both SO4- and
      OH species, but only OH signal was survived at alkaline condition. The leaked
      Fe2+ and Fe(II) of NP collectively work to activate PS and generate surface and
      bulk SO4- and OH simultaneously. The identified intermediates indicate the
      transformation of benzene ring is the key step for phenol degradation by NP/PS
      system. Moreover, phenol degradation was greatly inhibited in surface water (SW,
      29%) and wastewater (WW, 1%), but 25.9% and 17.5% of TOC removal were obtained in
      the SW and WW during NP/PS treatment, respectively. Additionally, the acute
      toxicity tests for NP/PS process exhibited a fluctuating trend depending on the
      water matrix, while the genotoxic activity analysis indicated that the treated
      phenol solutions were not genotoxic but cytotoxic. Overall, this study provides a
      solution to abate refractory organic micropollutants in water systems.

PMID- 28755552
TI  - Fabrication of novel nanoporous copper powder catalyst by dealloying of ZrCuNiAl
      amorphous powders for the application of wastewater treatments.
AB  - The nanoporous copper (Cu) powders (NPCPs) co-existing with Cu2O was fabricated
      by dealloying of atomized Zr-Cu-Ni-Al amorphous powders. The as-fabricated NPCPs,
      with an inner core and outer shell, showed a large specific surface area of
      7.52m2g-1 and exhibited significantly superior degradation ability in the
      presence of hydrogen peroxide (H2O2) for the complete elimination of methyl
      orange (MO) under both acidic and neutral environments. The enhanced catalytic
      decomposition properties of H2O2 by NPCPs were mainly attributed to the large
      specific surface area and three-dimensional continuous nanoporous structure with
      unique atomic steps on the ligament surfaces. The mechanistic investigations
      revealed that Cu2O/H2O2 reactions in acidic environment and Cu0/H2O2 reactions in
      neutral environment, respectively, were responsible for the high degradability of
      azo dyes, indicating that NPCPs/H2O2 could be a good Fenton-like reagent in
      application of wastewater treatments.

PMID- 28755553
TI  - Remediation of 137Cs contaminated concrete using electrokinetic phenomena and
      ionic salt washes in nuclear energy contexts.
AB  - This work describes the first known the use of electrokinetic treatments and
      ionic salt washes to remediate concrete contaminated with 137Cs. A series of
      experiments were performed on concrete samples, contaminated with K+ and 137Cs,
      using a bespoke migration cell and an applied electric field (60V potential
      gradient and current limit of 35mA). Additionally, two samples were treated with
      an ionic salt wash (<=400molm-3 of KCl) alongside the electrokinetic treatment.
      The results show that the combined treatment produces removal efficiencies three
      times higher (>60%) than the electrokinetic treatment alone and that the
      decontamination efficiency appears to be proportional to the initial degree of
      contamination. Furthermore, the decontamination efficiencies are equivalent to
      previous electrokinetic studies that utilised hazardous chemical enhancement
      agents demonstrating the potential of the technique for use on nuclear licensed
      site. The results highlight the relationship between the initial contamination
      concentration within the concrete and achievable removal efficiency of
      electrokinetic treatment and other treatments. This information would be useful
      when selecting the most appropriate decontamination techniques for particular
      contamination scenarios.

PMID- 28755554
TI  - Association between plasma concentrations of vitamin D metabolites and depressive
      symptoms throughout pregnancy in a prospective cohort of Brazilian women.
AB  - Plasma concentrations of vitamin D metabolites can be inversely associated with
      depressive symptoms. However, few longitudinal studies have investigated this
      association, especially during pregnancy. The aim of this study was to
      investigate the association between concentrations of 25-hydroxyvitamin D
      [25(OH)D] and 1,25-dihydroxivitamin D [1,25(OH)2D] with the occurrence of
      depressive symptoms throughout pregnancy. A prospective cohort of 179 women was
      followed at 5th-13th, 20th-26th and 30th-36th gestational weeks. At each
      trimester of pregnancy, the plasma concentrations of 25(OH)D and 1,25(OH)2D were
      analyzed by liquid chromatography tandem mass spectroscopy. Vitamin D status was
      categorized according to the Endocrine Society Practice Guidelines and the
      Institute of Medicine. Depressive symptoms were measured at each trimester using
      the Edinburgh Postnatal Depressive Scale (cutoff >=13). Statistical analyses
      included random intercept logistic regression models for longitudinal analyses.
      In the first trimester, the prevalence of 25(OH)D <75, <50 and <30 nmol/L were
      69.3%, 14.0% and 1.7%, respectively. Prevalence of depressive symptoms were
      20.1%, 14.7% and 7.8% for the first, second and third trimesters, respectively.
      The probability of occurrence of depressive symptoms decreased throughout
      pregnancy (p-value = 0.005). Women with higher concentrations of 25(OH)D in the
      first trimester presented a lower odds ratio (OR) for the development of
      depressive symptoms during pregnancy (OR = 0.98; 95%CI: 0.96 to 0.99, p-value =
      0.047) in the adjusted model. In conclusion, there was a higher prevalence of
      vitamin D inadequacy and depressive symptoms during the first trimester. Higher
      25(OH)D concentrations in the first trimester were associated with a decrease of
      2% in the odds for presenting depressive symptoms throughout pregnancy.

PMID- 28755555
TI  - Determination of endogenous and exogenous corticosteroids in bovine urine and
      effect of fighting stress during the "Batailles des Reines" on their
      biosynthesis.
AB  - Natural corticosteroids include two families of substances: mineralocorticoids
      and glucocorticoids. Several drugs of similar structure and biological activity
      have been synthesized and are currently used in the clinical practice. Beside
      legal pharmacological treatments, these drugs have been consistently misused in
      animal breeding. One of the most abused corticosteroids is prednisolone. For many
      years, prednisolone has been considered of exclusive synthetic origin, but
      nowadays a debate about its possible endogenous production is under way. Several
      studies have been addressed to ascertain the potential relationship between
      stressful conditions, such as transportation and slaughtering, and endogenous
      production of prednisolone. In order to verify further the effect of stressful
      conditions, our laboratory analysed urine samples collected from the cows
      participating to the "Batailles des Reines" (a traditional contest based on
      ritual and spontaneous fights of pregnant cows), to verify if an endogenous
      prednisolone production may occur in these animals. We developed and validated a
      LC-MS/MS method for the simultaneous determination of cortisol, cortisone,
      prednisolone and five of its metabolites. The method was applied to the analysis
      of urine samples collected from "Batailles des Reines" competitions in 2012 and
      2013. All these samples had been previously analysed within an anti-doping
      control program and tested compliant to all screenings.

PMID- 28755556
TI  - A meta-analysis of cortisol concentration, vocalization, and average daily gain
      associated with castration in beef cattle.
AB  - A systematic review and meta-analysis (MA) were performed to summarize all
      scientific evidence for the effects of castration in male beef cattle on welfare
      indicators based on cortisol concentration, average daily gain (ADG), and
      vocalization. We searched five electronic databases, conference proceedings, and
      experts were contacted electronically. The main inclusion criteria involved
      completed studies using beef cattle up to one year of age undergoing surgical and
      non-surgical castration that presented cortisol concentration, ADG, or
      vocalization as an outcome. A random effect MA was conducted for each indicator
      separately with the mean of the control and treated groups. A total of 20
      publications reporting 26 studies and 162 trials were included in the MA
      involving 1814 cattle. Between study heterogeneity was observed when analysing
      cortisol (I2=56.7%) and ADG (I2=79.6%). Surgical and non-surgical castration
      without drug administration compared to uncastrated animals showed no change
      (P>=0.05) in cortisol level. Multimodal therapy for pain did not decrease
      (P>=0.05) cortisol concentration after 30min when non-surgical castration was
      performed. Comparison between surgical castration, with and without anaesthesia,
      showed a tendency (P=0.077) to decrease cortisol levels after 120min of
      intervention. Non-surgical and surgical castration, performed with no pain
      mitigation, increased and tended to increase the ADG by 0.814g/d (P=0.001) and by
      0.140g/d (P=0.091), respectively, when compared to a non-castrated group. Our MA
      study demonstrates an inconclusive result to draw recommendations on preferred
      castration practices to minimize pain in beef cattle.

PMID- 28755557
TI  - Amphiphilic gemini pyridinium-mediated incorporation of Zn(II)meso-tetrakis(4
      carboxyphenyl)porphyrin into water-soluble gold nanoparticles for photodynamic
      therapy.
AB  - Zn-containing porphyrins are intensely investigated for their ability to form
      reactive oxygen species and thereby being potent photosensitizers for use in
      photodynamic therapy (PDT). Some of the drawbacks of the PDT approach, such as
      unspecific distribution, could be addressed by means of photosensitizer drug
      delivery systems. In this work, we synthesize and characterize new water-soluble
      gold nanoparticles (GNP) stabilized by a mixture of a polyethyleneglycol
      containing thiol (to improve water solubility) and a new amphiphilic gemini-type
      pyridinium salt, which also acts as promotor of the incorporation of the anionic
      photosensitizer Na-ZnTCPP into the GNP. The obtained GNP have sizes between 7 and
      10nm, as observed by Transmission Electron Microscopy. The incorporation of the
      photosensitizer caused an increase in the hydrodynamic size, detected by Dynamic
      Light Scattering, as well as a shift in the Surface Plasmon Resonance peak on the
      GNP UV-vis absorption spectra. The presence of the photosensitizer in the GNP was
      corroborated using Fluorescence Spectroscopy. The amount of Na-ZnTCPP was found
      to be 327 molecules per GNP. The porphyrin-containing Na-ZnTCPP-1.GNP showed good
      enhanced ability to produce singlet oxygen, compared to free Na-ZnTCPP. Their
      cytotoxicity and phototoxicity were investigated in vitro using two different
      human breast cell lines, one of tumoral origin (SKBR-3) and another of normal
      epithelium origin (MCF-10A). SKBR-3 cells showed higher sensitivity to Na-ZnTCCP
      and Na-ZnTCPP-1.GNP in dark conditions. After irradiation, no significant
      differences were observed between both cell lines except for 1MUM Na-ZnTCCP-1.GNP
      where SKBR-3 cells were also more sensitive.

PMID- 28755558
TI  - Tenofovir disoproxil fumarate loaded PLGA nanoparticles for enhanced oral
      absorption: Effect of experimental variables and in vitro, ex vivo and in vivo
      evaluation.
AB  - In this study, PLGA based nanoparticles of tenofovir disoproxil fumarate (TDF)
      were designed for enhancing its oral absorption. To develop PLGA based TDF
      nanoparticles with the goal of minimum particle size and maximum entrapment
      efficiency statistical optimization techniques (factorial design and response
      surface methodology) were employed. The optimized nanoparticles were
      characterized for size, shape, charge and physical state. Further, the stability,
      cytotoxicity and metabolic protective effect of the nanoparticles were evaluated.
      Single dose pharmacokinetic study in rats was conducted to evaluate the oral
      absorption of the designed nanoparticles. Ex vivo everted gut sac studies were
      performed to evaluate the role of active uptake mechanisms in the absorption of
      the designed nanoparticles. The results showed that the statistical models
      employed could determine the interaction effects of the critical factors which
      were used in the optimization of the nanoparticles. The optimized nanoparticles
      with a particle size of 218+/-3.85nm and an entrapment efficiency of 57.3+/-1.6%.
      The nanoparticles were able to increase the AUC of tenofovir by 5.8 fold. It was
      observed that active uptake mechanisms predominantly via clathrin-mediated uptake
      played a key role in increasing the oral absorption of TDF.

PMID- 28755559
TI  - Shear flow induced long-range ordering of rod-like viral nanoparticles within
      hydrogel.
AB  - Controlling the alignment of anisotropic nanoparticles within a three-dimensional
      (3D) environment over large-scale is still a challenge. In this paper, a facile
      method to align rod-like nanoparticles in hydrogel via shear flow to afford a
      long-range order is reported. The rod-like tobacco mosaic virus (TMV) was
      employed as a prototypical anisotropic particles in the study, and the shear
      force provided by the unidirectional flow of the precursor solution direct the
      alignment of TMVs, which could be quickly fixed through the fast sol-gel
      transition in situ. The degree of orientation and the distance between the TMV
      particles could be regulated by adjusting the concentration of hydrogels and
      TMVs. While the introduction of TMVs could reduce the degree of swelling of the
      hydrogel and help maintaining the mechanical strength of resultant hydrogels,
      both repulsion interaction and shear flow contributed synergistically to the
      assembly. This method does not require the usage of strong magnetic or electric
      fields, nor does it require the use of specialized lithography, thus offers a
      facile way to the fabrication of hydrogel materials with control of anisotropic
      structural features.

PMID- 28755560
TI  - Implicit and explicit drinking identity predict latent classes that differ on the
      basis of college students' drinking behaviors.
AB  - BACKGROUND: The purpose of this study was to identify distinct classes of college
      students on the basis of recent and past drinking behaviors and evaluate how
      implicit and explicit measures of drinking identity predict membership in these
      classes. METHODS: US undergraduate students (N=456) completed online implicit
      (Implicit Association Test) and explicit (self-report) measures of drinking
      identity and assessments of drinking behaviors, including past month drinking, at
      risk drinking in the past year, and lifetime history of intoxication. Latent
      class analysis (LCA) was used to identify classes of college students based on
      their drinking behaviors. RESULTS: LCA identified five classes: (1) Lifetime
      Nondrinker, (2) Recent Nondrinker/Past Risk, (3) Light Drinker, (4) Moderate
      Drinker, and (5) Heavy Drinker. Overall, stronger implicit and explicit drinking
      identities were uniquely associated with greater odds of belonging to classes
      with greater alcohol consumption and related consequences relative to those
      classes characterized by lower alcohol consumption and consequences. Notably,
      explicit drinking identity was positively associated with odds of membership to
      the Recent Nondrinker/Past Risk class relative to the Lifetime Nondrinker and
      Light Drinker classes, and implicit and explicit drinking identities were
      positively associated with odds of membership to the Heavy Drinker class relative
      to all other classes. CONCLUSIONS: Findings suggest that drinking identity is
      sensitive to risky drinking experiences in the past, is especially strong among
      the highest-risk group of college student drinkers, and may be an important
      cognitive factor to consider as a target for intervention.

PMID- 28755561
TI  - Measurement of the environmental broadband electromagnetic waves in a mid-size
      European city.
AB  - In this paper, the level of exposure to broadband radiofrequency electromagnetic
      field in a mid-size European city was evaluated in accordance with the
      International Commission on Non-ionizing Radiation Protection guidelines from
      1998. With the aim to analyse all the potential electromagnetic waves present in
      the city up to 18GHz, a total of 271 locations distributed along Terrassa (Spain)
      have been measured. To show the results in an easy-to-interpret way by the
      citizen, the results have been represented in a set of raster maps. The
      measurement results obtained showed that the electromagnetic wave measured in all
      broadband frequency range along the city is much lower than the safety level
      according to the international regulations for both public and occupational
      sectors.

PMID- 28755562
TI  - Stabilisation of dental structures of severely incinerated victims at disaster
      scenes to facilitate human identification.
AB  - Fatalities due to fire events such as bushfires, domestic and industrial fires
      and vehicle accident related incineration, leave victims with limited prospects
      of being accurately identified. Due to their morphology and anatomical position
      teeth are uniquely protected in incineration cases and via comparison to dental
      records often provide the only scientifically valid means of identification.
      However, extreme heat and direct exposure to flame can render the teeth extremely
      fragile and vulnerable to damage and loss especially during collection and
      transportation to the mortuary. Here we highlight the advantages of forensic
      odontology assistance at the scene of such events and discuss techniques and
      protocols applied to actual cases in which these processes were used to
      facilitate the identification of incineration victims.

PMID- 28755563
TI  - Synthesis and antioxidant ability of 6,6'-diamino-6,6'-dideoxytrehalose.
AB  - In order to study the influence of amino group on antioxidant activity of
      oligosaccharides, an amino disaccharide, 6,6'-diamino-6,6'-dideoxytrehalose
      (DAMDT) was successfully prepared in this paper, and its antioxidant activities
      against DPPH, superoxide, hydrogen peroxide, and hydroxyl radicals, and reducing
      power were evaluated, respectively. The results indicated that DAMDT had better
      antioxidant activity than trehalose at any tested concentration. The influence of
      amino group on antioxidant activity of disaccharides is positive based on the
      results in this paper, and amination should be an effective method to improve the
      bioactivity of saccharides.

PMID- 28755564
TI  - Measurements of Argon-39 at the U20az underground nuclear explosion site.
AB  - Pacific Northwest National Laboratory reports on the detection of 39Ar at the
      location of an underground nuclear explosion on the Nevada Nuclear Security Site.
      The presence of 39Ar was not anticipated at the outset of the experimental
      campaign but results from this work demonstrated that it is present, along with
      37Ar and 85Kr in the subsurface at the site of an underground nuclear explosion.
      Our analysis showed that by using state-of-the-art technology optimized for
      radioargon measurements, it was difficult to distinguish 39Ar from the fission
      product 85Kr. Proportional counters are currently used for high-sensitivity
      measurement of 37Ar and 39Ar. Physical and chemical separation processes are used
      to separate argon from air or soil gas, yielding pure argon with contaminant
      gases reduced to the parts-per-million level or below. However, even with
      purification at these levels, the beta decay signature of 85Kr can be mistaken
      for that of 39Ar, and the presence of either isotope increases the measurement
      background level for the measurement of 37Ar. Measured values for the 39Ar
      measured at the site ranged from 36,000 milli- Becquerel/standard-cubic-meter-of
      air (mBq/SCM) for shallow bore holes to 997,000 mBq/SCM from the rubble chimney
      from the underground nuclear explosion.

PMID- 28755565
TI  - Automatic plume episode identification and cloud shine reconstruction method for
      ambient gamma dose rates during nuclear accidents.
AB  - Ambient gamma dose rate (GDR) is the primary observation quantity for nuclear
      emergency management due to its high acquisition frequency and dense spatial
      deployment. However, ambient GDR is the sum of both cloud and ground shine, which
      hinders its effective utilization. In this study, an automatic method is proposed
      to identify the radioactive plume passage and to separate the cloud and ground
      shine in the total GDR. The new method is evaluated against a synthetic GDR
      dataset generated by JRODOS (Real Time On-line Decision Support) System and
      compared with another method (Hirayama, H. et al., 2014. Estimation of I-131
      concentration using time history of pulse height distribution at monitoring post
      and detector response for radionuclide in plume. Transactions of the Atomic
      Energy Society of Japan 13:119-126, in Japanese (with English abstract)). The
      reconstructed cloud shine agrees well with the actual values for the whole
      synthetic dataset (1451 data points), with a very small absolute fractional bias
      (FB = 0.02) and normalized mean square error (NMSE = 2.04) as well as a large
      correlation coefficient (r = 0.95). The new method significantly outperforms the
      existing one (more than 95% reduction of FB and NMSE, and 61% improvement of the
      correlation coefficient), mainly due to the modification for high deposition
      events. The code of the proposed methodology and all the test data are available
      for academic and non-commercial use. The new approach with the detailed
      interpretation of the in-situ environment data will help improving the ability of
      off-site source term inverse estimation for nuclear accidents.

PMID- 28755566
TI  - Chemical reprogramming and transdifferentiation.
AB  - The revolutionizing somatic cell reprogramming/transdifferentiation technologies
      provide a new path for cell replacement therapies and drug screening. The
      original method for reprogramming involves the delivery of exogenous
      transcription factors, leading to the safety concerns about the possible genome
      integration. Many efforts have been taken to avoid genetic alteration in somatic
      cell reprogramming/transdifferentiation by using non-integrating gene delivery
      approaches, cell membrane permeable proteins, and small molecule compounds.
      Compared to other methods, small-molecule compounds have several unique
      advantages, such as structural versatility and being easy to control in a time
      dependent and concentration-dependent way. More importantly, small molecules have
      been used as drugs to treat human diseases for thousands of years. So the small
      molecule approach to reprogramming might be more acceptable in clinical-related
      uses. In the past few years, small molecule approaches have made significant
      progresses in inducing pluripotent or functional differentiated cells from
      somatic cells. Here we review the recent achievements of chemical
      reprogramming/transdifferentiation and discuss the advantages and challenges
      facing this strategy in future applications.

PMID- 28755567
TI  - Microcephaly and Zika virus: Neuroradiological aspects, clinical findings and a
      proposed framework for early evaluation of child development.
AB  - BACKGROUND AND AIMS: As the recent outbreak of microcephaly cases caused by Zika
      virus has been declared a global health emergency, providing assessment
      guidelines for multidisciplinary teams providing early developmental screening
      and stimulation to infants with microcephaly is much needed. Thus, the aim of
      this manuscript is to provide an overview on what is known about
      neuroradiological aspects and clinical findings in infants with microcephaly
      caused by Zika virus and to propose a framework for early evaluation of child
      development. METHODS: The keywords "Zika virus" and "microcephaly" were searched
      in PubMed database for articles published from incept to May 2017. These texts
      were reviewed, and the ones addressing neuroradiological and clinical findings in
      infants were selected. Recommendations for early assessment were made based on
      the International Classification of Functionality Disability and Health (ICF)
      model. OUTCOMES AND RESULTS: The database search yielded 599 publications and 36
      were selected. The studies detected microcephaly with diffuse brain malformations
      and calcifications, ventriculomegaly, optic nerve hypoplasia, macular atrophy,
      cataracts, impaired visual and hearing function, arthrogryposis, spasticity,
      hyperreflexia, irritability, tremors, and seizures, but very little is known
      about early development. Early assessments were described based on the ICF
      domains (Body Function and Structures, Activities and Participation and
      Contextual factors). CONCLUSION AND IMPLICATIONS: Studies published showed
      abnormal brain, optic, neurologic and orthopedic findings, but very little is
      known about other aspects of functioning in infants with microcephaly caused by
      Zika virus. The biopsychosocial model based on the ICF paradigm provides an
      adequate framework to describe the condition of the infant with microcephaly
      receiving rehabilitative efforts to minimize disability. Efforts towards early
      identification of developmental delays should be taken within the first six
      months of life.

PMID- 28755568
TI  - What patients think about psychogenic nonepileptic seizures in Buenos Aires,
      Argentina: A qualitative approach.
AB  - PURPOSE: To analyse the methods of reasoning with regard to patients' experiences
      of living with psychogenic nonepileptic seizures (PNES) in Buenos Aires,
      Argentina. METHOD: A qualitative approach using semi-structured interviews was
      used to gain an in-depth and contextual understanding of the perspectives of five
      patients with PNES. Data collection and analysis were followed by an inductive
      and interpretive approach informed by the principles of thematic analysis.
      RESULTS: Explanatory models and prototypes were identified from the patients'
      narratives. Four patients related their suffering regarding psychosocial causes 
      family conflicts, sexual harassment, and life changes, among others-. Hereditary
      and organic hypotheses appeared to be unspecific. Folk explanations were common
      to all participants (magic, witchcraft, energetic causes). Four patients used the
      term epilepsy as an illness prototype, focusing on seizures and the use of
      antiepileptic drugs. Three of them also compared their illness to other people's
      "attacks" (heart attacks, panic attacks, nervous breakdown). Only one of them
      referred to someone who was suspected of having epilepsy. CONCLUSION: Patients'
      psychosocial explanatory models are different from the results of previous
      studies because these studies indicate that most patients support somatic
      explanations. Patients also use folk explanations related to traditional
      medicine, which highlights the interpersonal aspects of the disease. Doctor
      patient communication is essential for a correct understanding of PNES, resulting
      in better outcomes. It could also help to reduce the cultural distance between
      professionals and patients, leading to narrowing inequalities present in
      multicultural healthcare services.

PMID- 28755569
TI  - The impact of methods to handle missing data on the estimated prevalence of
      dementia and mild cognitive impairment in a cross-sectional study including non
      responders.
AB  - OBJECTIVE: Although several statistical methods for adjusting for missing data
      have been developed and are widely applied in research, few studies have
      investigated these methods in adjusting for missingness in datasets that aim to
      estimate the prevalence of dementia. We attempted to develop a more feasible
      approach for handling missingness in a cross-sectional study among elderly.
      METHODS: Five methods of estimating prevalence, including stratified weighting
      (SW), inverse-probability weighting (IPW), hot deck imputation (HDI), ordinal
      logistic regression (OLR) and multiple imputation (MI), were applied to handle
      the missing data yielded by a dataset that include 2231 non-responders. RESULTS:
      Compared with the results of the complete case analysis, the differences in the
      prevalence rates of dementia and mild cognitive impairment (MCI) calculated by
      the prevalence-estimating methods after adjusting for non-responders were less
      than 7% and 6%, respectively. In contrast to the results of other methods, the
      estimated prevalence of dementia and MCI calculated by MI increased when more
      predictive factors were included, and the lowest rate of missing data was
      achieved using MI. Using the participants' ages, the cognitive screening sores
      and activity of daily life sores as predictive variables when correcting for
      missingness induced relatively larger effects on the estimated dementia
      prevalence. CONCLUSIONS: When adjusting for missingness while estimating the
      prevalence of dementia in cross-sectional studies, a simple method, such as SW,
      is recommended when limited information is available, whereas MI is the preferred
      method when additional information is available. Further simulation studies are
      needed to determine the optimal approach.

PMID- 28755570
TI  - Young peoples' perceptions of the nursing profession: An integrative review.
AB  - OBJECTIVES: The purpose of this integrative review was to describe young people's
      perceptions of the nursing profession and to identify factors influencing the
      perception. DESIGN: Integrative literature review. DATA SOURCES: The CINAHL,
      PubMed and Medic electronic databases were searched for research publications
      between 2006 and 2016. The keywords used were: perception, attitude, belief,
      view, knowledge, image, nurse, nursing care, career, profession, role, teen,
      middle school student, high school student, adolescent and pupil. A manual search
      was conducted of the reference lists of the identified articles. REVIEW METHODS:
      Whittemore and Knafl's method for conducting an integrative review was utilized.
      The quality of the chosen articles was assessed with Joanna Briggs Institute's
      quality appraisal tools. FINDINGS: The search resulted in eight articles. Young
      people described the nature of nursing work with poor working conditions, shift
      work and a limited level of autonomy. Nursing work was mainly seen as caring for
      and helping patients which was considered inferior to doctors' work. Young people
      did not recognize the educational requirements or the career pathways in nursing
      and described the status of nursing as low in society. Nurses were considered as
      kind and caring people who work hard and are less intellectual. The factors
      influencing the perception were family and relatives, friends, media, significant
      others and personal factors. CONCLUSIONS: Perceptions of young people do not
      reflect the reality of the nursing profession and the perceived image of nursing
      has not changed in the last ten years. Young people and the public need realistic
      information of the nursing profession and the actions to change the image should
      take place at all levels of the society. Further research is needed to understand
      how the perceptions of the young people can be influenced and changed to reflect
      a more realistic image of a contemporary nurse.

PMID- 28755571
TI  - Participation in cross-national learning assessments and impact on capacity
      development: Programmes, practice, structures and teacher competency. Case study
      of Kenya, Tanzania and South Africa.
AB  - This research is one of the few attempts to employ the conceptual framework of
      "technology transfer" to analyze the extent that participation in cross-national
      learning assessments has had on capacity development, particularly in the
      development of official public structures, by equipping educationists and
      influencing teachers' competency in Kenya, Tanzania and South Africa. The
      researchers conducted semi-structured interviews with key informants drawn from
      the Ministries of Basic Education, national examinations councils, civil society
      organizations and curriculum development institutions in the three countries. The
      in-depth interviews were complemented by relevant literature on this topic. The
      study established improved technical capacities in the public education sector in
      South Africa and Kenya to design and conduct independent large-scale learning
      assessments. This important research demonstrates a certain level of commitment
      by African countries to establish official structures necessary to
      design/implement and sustain a culture of monitoring learning outcomes through
      public funded large-scale learning assessments. The research potentially
      contributes to the body of knowledge as far as 'summative' evaluation and
      analysis of the theory of change underpinning the participation in cross-national
      learning assessments espoused under the Education for All (EFA) Framework of
      Action.

PMID- 28755572
TI  - Reality monitoring performance and the role of visual imagery in visual
      hallucinations.
AB  - BACKGROUND: Auditory Hallucinations may arise from people confusing their own
      inner speech with external spoken speech. People with visual hallucinations (VH)
      may similarly confuse vivid mental imagery with external events. This paper
      reports two experiments exploring confusion between internal and external visual
      material. METHOD: Experiment 1 examined reality monitoring in people with
      psychosis; those with visual hallucinations (n = 16) and those without (n = 15).
      Experiment 2 used two non-clinical groups of people with high or low
      predisposition to VH (HVH, n = 26, LVH, n = 21). All participants completed the
      same reality monitoring task. Participants in Experiment 2 also completed
      measures of imagery. RESULTS: Psychosis patients with VH demonstrated biased
      reality monitoring, where they misremembered items that had been presented as
      words as having been presented as pictures. Patients without VH did not show this
      bias. In Experiment 2, the HVH group demonstrated the same bias in reality
      monitoring that psychosis patients with VH had shown. The LVH group did not show
      this bias. In addition, the HVH group reported more vivid imagery and
      particularly more negative imagery. CONCLUSIONS: Both studies found that people
      with visual hallucinations or prone-ness to such experiences confused their inner
      visual experiences with external images. Vivid imagery was also related to
      proneness to VH. Hence, vivid imagery and reality monitoring confusion could be
      contributory factors to understanding VH.

PMID- 28755573
TI  - Heteroleptic oxidovanadium(IV) complexes of 2-hydroxynaphtylaldimine and
      polypyridyl ligands against Trypanosoma cruzi and prostate cancer cells.
AB  - In Latin America Chagas disease is an endemic illness caused by the parasite
      Trypanosoma cruzi (T. cruzi), killing more people than any other parasitic
      disease. Current chemotherapies are old and inadequate, thus the development of
      efficient ones is urgently needed. Vanadium-based complexes have been shown to be
      a promising approach both against parasitic diseases and cancer and this study
      aims to achieve significant advances in the pursue of effective compounds.
      Heteroleptic vanadium complexes of Schiff bases and polypyridine compounds were
      prepared and their stability in solution evaluated by EPR (Electronic
      Paramagnetic Resonance) and NMR spectroscopy. Their in vitro activities were
      evaluated against T. cruzi and a set of cells lines representative of human
      cancer conditions, namely ovarian, breast and prostate cancer. In T. cruzi, most
      of the complexes depicted IC50 values in the low MUM range, induced changes of
      mitochondrial membrane potential and apoptosis. In cancer cells, complexes showed
      good to moderate activity and in metastatic cells (prostate PC3), some complexes
      inhibited the migratory ability, this suggesting that they display antimetastatic
      potential. Interestingly, complex 5 seemed to have a dual effect being the most
      cytotoxic complex on all cancer cells and also the most active anti-T-cruzi
      compound of the series. Globally the complexes showed promising anticancer and
      anti T. cruzi activities and also displayed some characteristics indicating they
      are worth to be further explored as antimetastatic drugs.

PMID- 28755574
TI  - Impact of the Cu(II) ions on the chemical and biological properties of goserelin 
      coordination pattern, DNA degradation, oxidative reactivity and in vitro
      cytotoxicity.
AB  - Goserelin acetate (Gos) as a synthetic analog of the mammalian gonadotropin
      releasing hormone (GnRH) is widely used in the treatment of sex hormone-related
      conditions. In this paper we present the chemical and biological aspects of its
      interaction with Cu(II) ions. The mode of Cu(II) binding and the thermodynamic
      stability of the obtained complexes were characterized by potentiometry, UV-Vis
      and CD spectroscopic methods. The DFT calculations were applied in order to
      investigate and confirm the molecular structure of the studied systems. The
      experimental and theoretical results clearly indicated the involvement of three
      nitrogens from the peptide and two oxygens from the acetate moieties in the
      Cu(II) coordination under physiological conditions. The investigated
      metallopeptide caused single- and/or double cleavage of the sugar-phosphate
      backbone of the plasmid DNA in the reaction accompanied by endogenous substances
      such as hydrogen peroxide or ascorbic acid. The degradation of the DNA molecule
      occurred via the free radical mechanism. Calculations based on measured spectra
      allowed determining the kinetic parameters of OH formation. The cytotoxic effects
      of Gos and its metallo-derivative were tested in vitro towards two cancer cell
      lines (A549 - human lung adenocarcinoma, CT26 - mouse colon carcinoma).

PMID- 28755575
TI  - Protective effect of Dendrobium officinale polysaccharides on H2O2-induced injury
      in H9c2 cardiomyocytes.
AB  - The preliminary studies have shown that Dendrobium officinale possessed
      therapeutic effects on hypertension and atherosclerosis. Studies also reported
      that Dendrobium officinale polysaccharides showed antioxidant capabilities.
      However, little is known about its effects on myocardial cells under oxidative
      stress. The present study was designed to study the protective effect of
      Dendrobium officinale polysaccharides against H2O2-induced oxidative stress in
      H9c2 cells. MTT assay was carried out to determine the cell viability of H9c2
      cells when pretreated with Dendrobium officinale polysaccharides. Fluorescent
      microscopy measurements were performed for evaluating the apoptosis in H9c2
      cells. Furthermore, effects of Dendrobium officinale polysaccharides on the
      activities of antioxidative indicators (malondialdehyde, superoxide dismutase),
      reactive oxygen species (ROS) production and mitochondrial membrane potential
      (MMP) levels were analyzed. Dendrobium officinale polysaccharides attenuated H2O2
      induced cell death, as determined by the MTT assay. Dendrobium officinale
      polysaccharides decreased malondialdehyde levels, increased superoxide dismutase
      activities, and inhibited the generation of intracellular ROS. Moreover,
      pretreatment with Dendrobium officinale polysaccharides also inhibited apoptosis
      and increased the MMP levels in H9c2 cells. These results suggested the
      protective effects of Dendrobium officinale polysaccharides against H2O2-induced
      injury in H9c2 cells. The results also indicated the anti-oxidative capability of
      Dendrobium officinale polysaccharides.

PMID- 28755576
TI  - Hepatoprotective effect of Opuntia microdasys (Lehm.) Pfeiff flowers against
      diabetes type II induced in rats.
AB  - Opuntia sp. has long been used as a folk medicine to treat hepatitis and diabetes
      in Sicile (Italy). To extract the polyphenols from the flower of Opuntia
      microdasys Lehm. at post flowring stage and evaluate the antidiabetic activity in
      vitro and in vivo. The hepatoprotective activity of Opuntia microdasys aqueous
      flowers extract at post flowering stage (OFP) has been tested for their
      antidiabetic activity. On fructose-alloxan induced diabete in rat model,
      evaluating the inhibitory effects of OFP on some carbohydrate metabolizing
      enzymes, pancreatic alpha-amylase and intestinal alpha-glucosidase activities in
      vitro. The OFP extract showed inhibitory activity against alpha-glucosidase
      (IC50=0.17+/-0.012mg/ml) and alpha-amylase (IC50=2.55+/-0.41mg/ml). The
      inhibitory potential of OFP extract on these enzymes suggests a positive and
      probable role of this extract in the management and treatment of diabetes
      mellitus, particularly, for type 2. Oral administration of the OFP at 200mg/kg to
      diabetic male rats for 28days demonstrated a significant protective effect by
      lowering the levels of glucose (123.21+/-1.38mg/dL) and hepatic marker enzymes
      (AST, ALT, LDH, gamma-GT, BT, PAL, TC, LDL-C, HDL-C and TG). OFP attenuated
      oxidative stress by decreasing the SOD, CAT, GPX activity and the levels of PC
      and MDA in the liver and restored the histological architecture of the rat liver.
      OFP has protective effects on the protection of liver, thereby reducing some of
      the causes of diabetes in experimental animals.

PMID- 28755577
TI  - Flavonoids from Carya cathayensis Sarg. leaves inhibit carotid artery lesion
      formation induced by low blood flow.
AB  - The aim of the present study was to investigate the protective effect of the
      total flavonoids (TFs) from the leaves of Carya cathayensis Sarg. against early
      development of atherosclerosis. An in vivo model of carotid arterial partial
      ligation was established in mice, and the effects of TFs were investigated by
      morphometric measurements, Cell proliferation measurement and
      immunohistochemistry. The results showed that TFs could reduce neointima area by
      41%, and the adventitial thickening induced by partial ligation was remarkable
      inhibited by TFs treatment. medial SMCs proliferation was significantly inhibited
      in TFs treated group. Immunohistochemistry analyses demonstrated that mice with
      TFs treatment have significant less macrophages accumulation in adventitia. These
      findings indicated that TFs have inhibitory effect in early atherosclerosis
      lesion formation model and strong action on reduce the inflammation in vivo.

PMID- 28755578
TI  - Identification of Pelomyxa palustris Endosymbionts.
AB  - Pelomyxa palustris is a giant anaerobic/microaerobic amoeba, characterized by a
      number of exceptional cytological and physiological features, among them the
      presumed absence of energy producing organelles and the presence of endosymbiotic
      bacteria. These endosymbionts have been previously distinguished as: a large
      rectangular-shaped Gram-variable rod with a central cleft; a slender Gram
      negative rod; and a slender Gram-positive rod. Using DNA extracted from P.
      palustris cysts, we have obtained three SSU rRNA gene sequences. We have
      determined that these sequences are affiliated to three different prokaryotic
      genera: Methanosaeta (a methanogenic archaea), Syntrophorhabdus (a syntrophic
      Gram-negative bacteria) and Rhodococcus (an aerobic chemoorganotrophic Gram
      positive bacteria). To our knowledge, it is the first time that Syntrophorhabdus
      has been described as an endosymbiont in association with a methanogen.
      Strikingly, no traces of Methanobacterium formicicum could be detected, despite
      this methanogen had allegedly been isolated from trophozoites of P. palustris. It
      seems that the host and the endosymbionts have established a multipartite
      syntrophic consortium resembling to some extent those found in sewage treatment
      plants.

PMID- 28755579
TI  - Estradiol cypionate aided treatment for experimentally induced ascending
      placentitis in mares.
AB  - The overall goal of this study was to assess the efficacy of various therapeutic
      combinations of estradiol cypionate (ECP, a long-acting estrogen) and altrenogest
      (ALT, a long-acting progestin) in addition to basic treatment for placentitis
      with trimethoprim-sulfamethoxazole (TMS) and flunixin meglumine (FM). Specific
      outcomes measured in this experiment were (i) time from induction of bacterial
      placentitis to delivery, and foal parameters (high-risk, survival, and birth
      weight); and (ii) serum steroid concentrations (progesterone, 17alpha
      hydroxyprogesterone, 17beta-estradiol, and cortisol) in response to treatment.
      Pregnant mares (~300 days gestation, n = 46) were randomly assigned into healthy
      mares (control group, CONT, n = 8) and mares with experimentally induced
      ascending placentitis (n = 38). Placentitis was induced via intracervical
      inoculation of Streptococcus equi subspecies zooepidemicus. Thereafter,
      placentitis induced mares were randomly assigned into: (1) basic treatment,
      TMS+FM (n = 8); (2) basic treatment with ALT supplementation, TMS+FM+ALT (n = 8);
      (3) basic treatment with ECP supplementation, TMS+FM+ECP (n = 6); (4) basic
      treatment with ALT and ECP supplementation TMS+FM+ALT+ECP (n = 6); and (5) no
      treatment (INOC, n = 10). Treatments were started 48 h after bacterial
      inoculation and carried out for ten consecutive days. Blood samples were
      collected daily, and mares were assessed for signs of placentitis until the mare
      delivered, or for ten consecutive days after onset of treatment. Steroids were
      analyzed via RIA. Continuous data were analyzed by ANOVA, and categorical data
      analyzed by Fisher's exact test. Significance was set at p < 0.05. Foal survival
      at parturition and seven days post-delivery were similar across treated groups
      (66.7-100%), and to the CONT group. Similar to CONT group, mares in the
      TMS+FM+ECP group had no high-risk foals while mares in the other groups had
      higher incidences (50-75%) (p < 0.05). The inclusion of ECP in the treatments
      resulted in foals with body weight similar to CONT group (p > 0.05). There were
      no group effects or time by group interactions on concentrations of steroids
      assessed herein (p > 0.05). In conclusion, in addition to basic treatment TMS+FM,
      mares with experimentally induced ascending placentitis benefited from ECP
      supplementation. Conversely, ALT did not appear to make a difference in outcomes.
      The immunoassays used for measurements of steroid concentrations did not appear
      useful to assess treatment response.

PMID- 28755580
TI  - Green synthesized nickel nanoparticles for targeted detection and killing of S.
      typhimurium.
AB  - Simple and sensitive colorimetric immunosensor based on peroxidase mimetic
      activity and photothermal effect of nickel oxide nanoparticle (NiOGs) has been
      developed to detect and kill food borne pathogen Salmonella typhimurium. NiOGs
      showed superior peroxidase mimetic activity for oxidation of peroxidase substrate
      3, 3', 5, 5'-tetramethylbenzidine (TMB). Oxidation of TMB by NiOGs followed
      Michaelis-Menten kinetics with Km and Vmax values of 0.25mM and 2.64*10-8M/s
      respectively. NiOGs was coated with citric acid (CA-NiOGs) followed by
      conjugation with antibody (anti-S. typhimurium) (Ab-CA-NiOGs) that effectively
      captured S. typhimurium. Colorimetric detection of S. typhimurium by Ab-CA-NiOGs
      showed a linear relationship between pathogen concentration (1*101 to
      1*106cfu/mL) and color signal (652nm) with limit of detection (LOD) of 10cfu/mL.
      The proposed method showed no cross reactivity against other pathogens. Recovery
      of S. typhimurium in milk and juice samples was found to be 95 to 100% and 92 to
      99% respectively. NiOGs exposed to laser irradiation showed dose dependent
      increase in temperature and singlet oxygen within 5min. Bacteria bound to Ab-CA
      NiOGs after laser irradiation, induced membrane damage and reduced bacterial
      viability to 6%. The bifunctional peroxidase-mimetic activity and photothermal
      effect of NiOGs can be exploited in selective sensing and killing of target
      pathogens respectively in food products.

PMID- 28755581
TI  - Relationship between diminution of small pulmonary vessels and emphysema in
      chronic obstructive pulmonary disease.
AB  - OBJECTIVES: To investigate the relationship between small pulmonary vessels and
      extent of emphysema on CT in individual lungs with chronic obstructive pulmonary
      disease (COPD). METHODS: Forty-nine patients were included. The percentage of
      cross-sectional area of vessels <5mm2 (%CSA <5) and extent of emphysema were
      assessed. RESULTS: Less than half of the COPD patients demonstrated an inverse
      correlation between %CSA <5 and percentage of low attenuation area (LAA%). In the
      remaining patients, %CSA <5 was homogeneously distributed. CONCLUSION: Not all
      patients with COPD demonstrated an inverse correlation of the distributions
      between %CSA <5 and LAA% in individual lungs.

PMID- 28755582
TI  - Spectral Doppler ultrasound of peripheral arteries: a pictorial review.
AB  - This article reviews the pathophysiology and sonographic findings of peripheral
      arterial lesions, with emphasis on the spectral Doppler waveforms encountered in
      each. It discusses the characteristic features of the Doppler spectra in
      obstructive conditions, including thromboembolism, atherosclerotic disease,
      bypass graft occlusion, dissection, trauma, and compartment syndrome, as well as
      non-obstructive conditions, including hyperemia, pseudoaneurysm, and
      arteriovenous fistula. Familiarity with the commonly-encountered spectral
      waveforms in the setting of these lesions is necessary for timely and accurate
      diagnosis and treatment.

PMID- 28755583
TI  - Interaction of microorganisms within leafy green phyllospheres: Where do human
      noroviruses fit in?
AB  - Human noroviruses (hNoV) are one of the major causes of foodborne disease
      outbreaks linked to leafy greens. However, the interactions-including attachment
      and persistence-of hNoV with leafy greens are not well characterized. In the
      present review, three mechanisms are hypothesized for the interaction of hNoV
      with leafy green phyllospheres: 1) specific binding to histo-blood group antigen
      (HBGA)-like carbohydrates exposed on leaf surfaces and present on bacterial
      microbiota; 2) non-specific binding through electrostatic forces; and 3)
      internalization of hNoV through contaminated water (e.g. hydroponic feed water).
      To add more complexity, there is a rich diversity of microbial communities (i.e.,
      bacteria, fungi, protozoa) residing in leafy green phyllospheres, and the
      attachment and persistence of hNoV could be largely impacted by these
      microorganisms through direct and indirect interactions. For instance, enzymes
      produced by bacteria and fungi could potentially compromise the structure of HBGA
      like carbohydrate binding sites on leaves, leading to a reduction in hNoV
      binding. On the other hand, some bacteria also possess HBGA-like binding sites on
      their cell surface, which may provide extra binding locations for hNoV. There are
      also numerous metabolic compounds that can be produced by leafy greens and its
      microbial inhabitants and be subsequently distributed within leafy green
      phyllospheres. These compounds could theoretically play roles in enhancement or
      reduction in the attachment of hNoV. Overall, increasing the understanding of the
      various types of hNoV attachment and interactions with leafy green phyllospheres
      will be crucial for elucidating hNoV transmission via leafy greens as well as for
      the development of effective control measures.

PMID- 28755584
TI  - Family members' infant feeding preferences, maternal breastfeeding exposures and
      exclusive breastfeeding intentions.
AB  - BACKGROUND: Maternal breastfeeding intentions are strongly associated with
      breastfeeding exclusivity and duration. Factors that affect new mothers'
      exclusive breastfeeding intentions have not been adequately examined. OBJECTIVE:
      The purpose of this study was to examine the association between family member's
      infant feeding preferences, breastfeeding exposures, and womens' exclusive
      breastfeeding intentions. METHODS: 1277 breastfeeding mother-infant pairs were
      recruited from four public hospitals in Hong Kong. We used multiple logistic and
      linear regression models to explore the impact of the family members' infant
      feeding preferences and breastfeeding exposures on exclusive breastfeeding
      intentions. RESULTS: 78.1% mothers reported an intention to exclusively
      breastfeed, and the median intended duration of exclusive breastfeeding was 26
      weeks. The husband's preference for breastfeeding (aOR = 1.67; 95% CI 1.20-2.31),
      previous breastfeeding experience (aOR = 1.56; 95% CI 1.10-2.23) and attendance
      at an antenatal breastfeeding class (aOR = 2.09; 95% CI 1.45-3.02) were all
      strongly associated with higher maternal intention to exclusively breastfeed. For
      every additional family member who preferred breastfeeding, the odds of intending
      to exclusively breastfeed increased by 32% (aOR1.32; 95% CI, 1.13-1.55).
      Similarly, the proportion of participants intending to exclusively breastfeed
      increased progressively with more breastfeeding exposures. CONCLUSIONS: Including
      fathers and other significant family members in antenatal breastfeeding education
      can help to maximize breastfeeding support for the new mother and encourage new
      mothers to exclusively breastfeed.

PMID- 28755585
TI  - Evaluation of Asteraceae herbal extracts in the management of diabetes and
      obesity. Contribution of caffeoylquinic acids on the inhibition of digestive
      enzymes activity and formation of advanced glycation end-products (in vitro).
AB  - The study was performed to assess, for the first time, the in vitro anti-diabetic
      potential of ten Asteraceae plant extracts to inhibit the activity of digestive
      enzymes (alpha-amylase, alpha-, beta-glucosidases and lipase) responsible for
      hydrolysis/digestion of sugar and lipids. Prevention of advanced glycation end
      products (AGEs) formation was evaluated in bovine serum albumin/ribose glycation
      reaction model. The phytochemical profiles and caffeoylquinic acids (CQAs)
      contents were determined for the methanolic extract of each plant. Analyzed plant
      extracts exhibited significant inhibitory activity against key digestive enzymes
      linked to type II diabetes and obesity. A strong inhibition was observed for
      glucosidases and mild activity towards amylase and lipase (compared to reference
      compounds). Moreover, some extracts exhibited potent ability to prevent formation
      of AGEs, implicated in some diabetic complications. Caffeoylquinic acids were
      dominant in all plant extracts and findings demonstrate that these compounds are
      the most relevant hypoglycemic and anti-glycation agents. From the obtained
      results, Argyranthemum pinnatifidum, Helichrysum melaleucum, and Phagnalon lowei
      are good candidates for further development of phyto-pharmaceutical preparations
      as complementary therapy for diabetes and obesity control.

PMID- 28755586
TI  - An unusual cysteine VL87 affects the antibody fragment conformations without
      interfering with the disulfide bond formation.
AB  - The Cys residues are almost perfectly conserved in all antibodies. They
      contribute significantly to the antibody fragment stability. The relevance of two
      natural contiguous Cys residues of an anti-recombinant human-follicle stimulation
      hormone (rhFSH) in a format of single-chain variable fragment (scFv) was studied.
      This scFv contains 5 Cys residues: VH22 and VH92 in the variable heavy chain (VH)
      and VL23, VL87 and VL88 in the variable light chain (VL). The influence of two
      unusual contiguous Cys at positions VL87 and VL88 was studied by considering the
      wild type fragment and mutant variants: VL-C88S, VL-C87S, VL-C87Y. The analysis
      was carried out using antigen-binding ability measurement by indirect specific
      ELISA and a detailed molecular modeling that comprises homology methods, long
      molecular dynamics simulations and docking. We found that VL-C87 affected the
      antibody fragment stability without interfering with the disulfide bond
      formation. The effect of mutating the VL-C87 by a usual residue at this position
      like Tyr caused distant structural changes at the VH region that confers a higher
      mobility to the VH-CDR2 and VH-CDR3 loops improving the scFv binding to the
      antigen.

PMID- 28755587
TI  - Author's response to 'Are skin antiseptics for blood culture collection really
      equal? Commentary on Liu, W., et al., 2016 "Skin antiseptics in venous puncture
      site disinfection for preventing blood culture contamination: A Bayesian network
      meta-analysis of randomized controlled trials"'.

PMID- 28755588
TI  - Genomic characterization of Zika virus isolated from Indonesia.
AB  - Zika virus (ZIKV) JMB-185 strain was isolated from a febrile patient in Jambi,
      Indonesia in 2014. To understand its genetic characteristics, we performed whole
      genome sequencing using the Ion Torrent PGM platform on the supernatant of the
      first passage. The phylogenetic analysis showed that the isolate was not closely
      related to the Brazilian ZIKV associated with microcephaly or isolates from the
      recent Singapore Zika outbreak. Molecular evolution analysis indicated that JMB
      185 strain may have been circulating in the Southeast Asia region, including
      Indonesia since 2000. We observed high nucleotide sequence identity between
      Indonesia, Thailand, Singapore, and American strains although unique amino acid
      substitutions were also observed. This report provides information on the genomic
      characteristics of Indonesian ZIKV which may be used for further studies.

PMID- 28755589
TI  - Children's environmental health based on birth cohort studies of Asia.
AB  - Numerous studies have explored the associations between environmental pollutants
      and pediatric health. Recent studies have investigated the issue in Asia, but no
      systematic review has been published to date. This study aims to elucidate the
      issue by summarizing relevant epidemiologic evidence for cohorts in Asia, using
      information from the Birth Cohort Consortium of Asia (BiCCA). Environmental
      pollutants include mercury, environmental tobacco smoke (ETS), polychlorinated
      biphenyls (PCB), perfluoroalkyl substances (PFAS) and phthalates. This study
      sought to classify the effects of such compounds on fetal growth and pregnancy
      outcomes, neurodevelopment and behavioral problems, allergic disease and immune
      function and the endocrine system and puberty. These evidences showed ETS has
      been associated with infant birth weight, children's neurodevelopment and allergy
      disease; mercury and PCB have been shown to affect children's neurodevelopment;
      phthalate has effects on endocrine function; PFAS alters children's
      neurodevelopment, the endocrine system, and the allergic response. However, more
      consistent and coordinated research is necessary to understand the whole picture
      of single environmental and/or co-exposure and children's health. Therefore,
      harmonization and international collaboration are also needed in Asia.

PMID- 28755590
TI  - UV-initiated synthesis of a novel chitosan-based flocculant with high
      flocculation efficiency for algal removal.
AB  - In this study, maleyl chitosan-graft-polyacrylamide (MHCS-g-PAM), a novel
      chitosan-based flocculant, was prepared through UV irradiation, and maleyl
      chitosan (MHCS) was designed and prepared with maleic anhydride and acrylamide
      (AM) through maleyl acylation reaction. The effects of monomer concentration,
      MHCS-to-AM ratio, illumination time, initiator concentration, pH on viscosity,
      and grafting efficiency were investigated to optimize the synthesis of these
      substances. MHCS-g-PAM was characterized through Fourier transform infrared
      spectroscopy, nuclear magnetic resonance hydrogen spectroscopy, scanning electron
      microscopy, and thermal gravimetric analysis. Flocculation mechanisms in alga
      containing wastewater at various pH levels and dosages were examined in detail on
      the basis of zeta potential measurements. Zeta potential experiments indicated
      that the adsorption-bridging and charge neutralization mechanisms played an
      important role in algal removal. Flocculation tests on algal removal demonstrated
      that the flocculation performance of MHCS-g-PAM was more effective than that of
      cationic polyacrylamide, polyferric sulfate, and polymeric aluminium. The optimal
      Chl-a and COD removal rate obtained by MHCS-g-PAM was 98.6% and 94.9% at pH7 and
      4mg.L-1, respectively.

PMID- 28755591
TI  - Letter to Editor re Zhang et al. (2017).

PMID- 28755592
TI  - The toxicity of molybdate to freshwater and marine organisms. III. Generating
      additional chronic toxicity data for the refinement of safe environmental
      exposure concentrations in the US and Europe.
AB  - The freshwater and marine long-term ecotoxicity datasets used in the European
      REACH registration dossiers for molybdenum and molybdenum compounds resulted in
      the derivation of a HC5,50%,freshwater (38.2mgMo/L) and HC5,50%,marine
      (5.70mgMo/L) by means of the statistical extrapolation method. Both datasets,
      however, did not meet the US-EPA information requirements for deriving Final
      Chronic Values (FCV) that were based on chronic data. US-EPA compliance was
      achieved by generating chronic no-effect data for the freshwater benthic amphipod
      Hyalella azteca and the marine inland silverside fish Menidia beryllina, using
      sodium molybdate dihydrate as test substance. A 42d-EC10 of 44.6mgMo/L for
      reproduction was determined in a water-only exposure with H. azteca. For M.
      beryllina, a 37d-NOEC of 139mg mMo/L for standard length and blotted wet weight
      was found. Other endpoints (e.g., survival, hatching success) proved to be less
      sensitive. Data were added to the existing chronic toxicity datasets, together
      with new long-term no-effect values that were identified in open literature for
      brown trout Salmo trutta, the marine alga Isochrysis galbana, the marine snail
      Nassarius dorsatus and the marine barnacle Amphibalanus amphitrite. The updated
      data sets resulted in a freshwater and marine HC5,50% of 35.7 and 6.85mgMo/L,
      respectively. The same data sets were also used for the determination of US-EPA
      FCVs, where the FVCfreshwater was 36.1mg/L, and the FCVmarine was 3.85mgMo/L. As
      the Final Plant Values for both aquatic environments were higher than their
      respective FCVs, the Criterion Continuous Concentration (CCC) for molybdenum is
      equal to the FCV.

PMID- 28755593
TI  - The potential ecotoxicological impact of pharmaceutical and personal care
      products on humans and freshwater, based on USEtoxTM characterization factors. A
      Spanish case study of toxicity impact scores.
AB  - Pharmaceutical and personal care products (PPCPs) are being increasingly included
      in Life Cycle Assessment studies (LCAs) since they have brought into evidence
      both human and ecological adverse effects due to their presence in different
      environmental compartments, wastewater facilities and industry. Therefore, the
      main goal of this research was to estimate the characterization factors (CFs) of
      27 PPCPs widely used worldwide in order to incorporate their values into Life
      Cycle Impact Assessment studies (LCIA) or to generate a toxicity impact score
      ranking. Physicochemical properties, degradation rates, bioaccumulation,
      ecotoxicity and human health effects were collected from experimental data,
      recognized databases or estimated using EPI SuiteTM and the USEtoxTM software,
      and were subsequently used for estimating CFs. In addition, a Spanish toxicity
      impact score ranking was carried out for 49 PPCPs using the 27 newly calculated
      CFs, and 22 CFs already available in the literature, besides the data related to
      the occurrence of PPCPs in the environment in Spain. It has been highlighted that
      emissions into the continental freshwater compartment showed the highest CFs
      values for human effects (ranging from 10-9 to 10-3Cases.kg-1), followed by
      emissions into the air (10-9 to 10-5Cases.kg-1), soil (10-11 to 105Cases.kg-1)
      and seawater (10-12 to 10-4Cases.kg-1). CFs regarding the affectation of
      freshwater aquatic environments were the highest of those proceeding from
      emissions into continental freshwater (between 1 to 104PAF.m3.day.kgemission-1)
      due to the direct contact between the source of emission and the compartment
      affected, followed by soil (among 10-1 to 104PAF.m3.day.kgemission-1), and air
      (among 10-2 to 104PAF.m3.day.kgemission-1) while the lowest were the CFs of
      continental seawater (among 10-28 to 10-3PAF.m3.day.kgemission-1). Freshwater
      aquatic ecotoxicological CFs are much higher than human toxicity CFs,
      demonstrating that the ecological impact of PPCPs in aquatic environments must be
      a matter of urgent attention. According to the Spanish toxicity impact score
      calculated, the PPCPs with the highest impact are hormones, antidepressants,
      fragrances, antibiotics, angiotensin receptor blockers and blood lipid
      regulators, which have already been found in other kinds of score rankings. These
      results, which were not available until now, will be useful in order to perform
      better LCIA studies, incorporating the micro-pollutants whose CFs have been
      estimated, or in order to carry out single hazard/risk environmental impact
      assessments.

PMID- 28755594
TI  - Characteristics and applications of ecological soil substrate for rocky slope
      vegetation in cold and high-altitude areas.
AB  - Ecological restoration of steep rocky slopes generated by road cutting is usually
      difficult especially, in the cold and high-altitude environment, which is
      unfavorable for the growth of vegetation. With the focus on slope vegetation, an
      ecological soil substrate, synthesized with polyacrylamide (PAM), carboxymethyl
      cellulose (CMC), and Fly ash (FA) as the main components, was developed for spray
      seeding on the rocky slopes in cold and high-altitude regions, to provide a
      favorable environment for vegetation growth. The compositional effect of
      individual compound addition on the growth of vegetation and substrate properties
      was investigated using an orthogonal array experimental design. Based on ANOVA
      and orthogonal analysis, an ecological soil substrate (PCF) with 400g/m3 PAM,
      600g/m3 CMC, 1500g/m3 FA, and 50L/m3 of water was decided as the optimum PCF
      substrate. The optimum PCF substrate was then sprayed on a steep rocky slope in a
      cold and high-altitude region in Sichuan, China, for two years. The vegetation,
      as well as the physico-chemical properties, nutrient content, and mechanical
      properties of the field soil substrate, were examined over this duration. The
      field verification shows that the proposed PCF substrate is able to provide
      desirable nutrient contents and excellent physical and mechanical properties for
      vegetating the steep rocky slopes in cold and high-altitude areas.

PMID- 28755595
TI  - Predicting diffuse microbial pollution risk across catchments: The performance of
      SCIMAP and recommendations for future development.
AB  - Microbial pollution of surface waters in agricultural catchments can be a
      consequence of poor farm management practices, such as excessive stocking of
      livestock on vulnerable land or inappropriate handling of manures and slurries.
      Catchment interventions such as fencing of watercourses, streamside buffer strips
      and constructed wetlands have the potential to reduce faecal pollution of
      watercourses. However these interventions are expensive and occupy valuable
      productive land. There is, therefore, a requirement for tools to assist in the
      spatial targeting of such interventions to areas where they will have the biggest
      impact on water quality improvements whist occupying the minimal amount of
      productive land. SCIMAP is a risk-based model that has been developed for this
      purpose but with a focus on diffuse sediment and nutrient pollution. In this
      study we investigated the performance of SCIMAP in predicting microbial pollution
      of watercourses and assessed modelled outputs of E. coli, a common faecal
      indicator organism (FIO), against observed water quality information. SCIMAP was
      applied to two river catchments in the UK. SCIMAP uses land cover risk
      weightings, which are routed through the landscape based on hydrological
      connectivity to generate catchment scale maps of relative in-stream pollution
      risk. Assessment of the model's performance and derivation of optimum land cover
      risk weightings was achieved using a Monte-Carlo sampling approach. Performance
      of the SCIMAP framework for informing on FIO risk was variable with better
      performance in the Yealm catchment (rs=0.88; p<0.01) than the Wyre (rs=-0.36;
      p>0.05). Across both catchments much uncertainty was associated with the
      application of optimum risk weightings attributed to different land use classes.
      Overall, SCIMAP showed potential as a useful tool in the spatial targeting of FIO
      diffuse pollution management strategies; however, improvements are required to
      transition the existing SCIMAP framework to a robust FIO risk-mapping tool.

PMID- 28755596
TI  - Mechanisms of enhanced inorganic phosphorus accumulation by periphyton in paddy
      fields as affected by calcium and ferrous ions.
AB  - The effect of periphyton propagation in paddy fields on phosphorus biogeochemical
      cycling has received little attention. In this phytotron study, inorganic
      phosphorus (Pi) accumulation by periphyton was investigated for varying inputs of
      calcium [Ca(II)] or ferrous-iron [Fe(II)], and lighting conditions. Results
      indicated that additions of Ca(II) or Fe(II) enhanced abiotic accumulation of Pi
      by up to 16 times, and decreased solution Pi concentration by up to 50%,
      especially under light condition. The enhanced Pi accumulation into periphyton
      intensified with increasing Pi concentration, and Pi accumulation showed a
      positive linear relationship with Ca or Fe accumulation. Abiotic accumulation of
      Pi induced by Ca(II) was mainly through Ca-phosphate precipitation, and co
      precipitation of P with carbonates at pH>8. Accumulation with added Fe(II) was
      mainly considered to be through Fe(III) phosphate precipitation coupled with
      adsorption of Pi by ferric hydroxides. Moreover, Fe(II) was more effective than
      Ca(II) in promoting abiotic accumulation of Pi by periphyton. Our results
      indicate the potential for controlling environmental factors to enhance the role
      of periphyton in biogeochemical cycling and P-use efficiency in paddy rice fields
      and to reduce P discharged to neighboring water bodies.

PMID- 28755597
TI  - A 13-year study of dissolved organic carbon in rainwater of an agro-industrial
      region of Sao Paulo state (Brazil) heavily impacted by biomass burning.
AB  - This work presents the first comprehensive study of DOC in rainwater in a
      tropical agro-industrial region in central Sao Paulo State. The DOC
      concentrations ranged from 15 to 4992MUmolCL-1, with an overall volume weighted
      mean (VWM) of 288+/-17MUmolCL-1 (n=881). The number of fire spots accumulated
      within each year of this study was positively correlated to the VWM concentration
      of DOC in rainwater. During the whole study period, higher VWM DOC concentrations
      were found during the dry months, despite the phasing out of agricultural fires
      in sugar cane plantations. The evidence suggested that inputs of atmospheric
      soluble organic carbon from biomass burning exceeded those from vehicular fuel
      combustion and biogenic sources. In most cases, dilution of DOC according to
      precipitation volume was minimal, showing that in-cloud processes were dominant
      for this species. In contrast, most of the volatile dissolved organic carbon
      (VDOC) appeared to be removed from the atmosphere in the first milliliter or so
      of rain, showing a dominance of below-cloud scavenging. VDOC contributed a
      significant fraction of the DOC for 62% of the samples analyzed, ranging from 5.1
      to 488MUmolCL-1 (n=552). The average wet deposition flux of DOC was 49kgCha-1yr
      1, with VDOC accounting for 10% of the total. This dissolved carbon flux is
      higher than the estimated world average (34kgCha-1yr-1). The DOC in the rainwater
      was mostly labile (75% on average) and rapidly bioavailable (within days to
      weeks), in contrast to refractory dissolved carbon found in rainwater from
      regions where fossil fuel combustion is the dominant source. The findings of this
      work indicate that biomass burning can lead to important atmospheric inputs of
      readily available organic matter to land and to the open ocean.

PMID- 28755598
TI  - Response of stream benthic macroinvertebrates to current water management in
      Alpine catchments massively developed for hydropower.
AB  - The present work focuses on evaluating the ecological effects of hydropower
      induced streamflow alteration within four catchments in the central Italian Alps.
      Downstream from the water diversions, minimum flows are released as an
      environmental protection measure, ranging approximately from 5 to 10% of the mean
      annual natural flow estimated at the intake section. Benthic macroinvertebrates
      as well as daily averaged streamflow were monitored for five years at twenty
      regulated stream reaches, and possible relationships between benthos-based stream
      quality metrics and environmental variables were investigated. Despite the non
      negligible inter-site differences in basic streamflow metrics, benthic
      macroinvertebrate communities were generally dominated by few highly resilient
      taxa. The highest level of diversity was detected at sites where upstream minimum
      flow exceedance is higher and further anthropogenic pressures (other than
      hydropower) are lower. However, according to the current Italian normative index,
      the ecological quality was good/high on average at all of the investigated
      reaches, thus complying the Water Framework Directive standards.

PMID- 28755599
TI  - Leaf morphological variability and intraspecific taxonomic units for pedunculate
      oak and grayish oak (genus Quercus L., series Pedunculatae Schwz.) in Southern
      Carpathian Region (Romania).
AB  - Even though pedunculate oak (Quercus robur L.) and grayish oak (Quercus
      pedunculiflora K. Koch) have different ecological requirements, they have been
      considered as having low differentiation at the level of morphological traits and
      genetic variation. The leaf morphology for 862 trees has been assessed in 16
      natural populations, seven of Q. robur, eight of Q. pedunculiflora and a mixed
      forest were both taxa coexist. In total, fifteen descriptors have been analysed
      by using discriminant analysis, while it was found that with only four out of the
      fifteen leaf traits (abaxial pubescence, abaxial colour of the leaf, petiole
      length and basal shape of lamina) the two taxa could be clearly differentiated. A
      dendrogram has been constructed on the basis of these traits, where the
      populations of each taxon have been clustered together. PU and CL traits of Q.
      pedunculiflora were discussed for their adaptive value for drought resistance in
      the steppe habitats occupied by this taxon. Using the leaves' morphological
      descriptors and data from the literature, intra-taxonomic units (varieties, forms
      and sub-forms) have been identified in all analysed populations. Eight
      intraspecific units for Q. robur and six for Q. pedunculiflora have been
      identified in the investigated area. An analysis of spatial distribution of the
      two taxa and of their intraspecific units has been performed using maps of
      ecoregions for the study area.

PMID- 28755600
TI  - Environmental factors exert strong control over the climate-growth relationships
      of Picea abies in Central Europe.
AB  - The growth response of trees to changing climate is frequently discussed as
      increasing temperatures and more severe droughts become major risks for forest
      ecosystems. However, the ability of trees to cope with the changing climate and
      the effects of other environmental factors on climate-growth relationships are
      still poorly understood. There is thus an increasing need to understand the
      ability of individual trees to cope with changing climate in various
      environments. To improve the current understanding, a large tree-ring network
      covering the whole area of the Czech Republic (in 7*7km grids) was utilized to
      investigate how the climate-growth relationships of Norway spruce are affected by
      1) various geographical variables, 2) changing levels of acidic deposition, 3)
      soil characteristics and 4) age, tree diameter and neighbourhood competition. The
      period from 1930 to 2013 was divided into four, 21-year long intervals of
      differing levels of acidic deposition, which peaked in the 1972-1993 period. Our
      individual-based, spatiotemporal, multivariate analyses revealed that spruce
      growth was mostly affected by drought and warm summers. Drought plays the most
      important negative role at lower altitudes, while the positive effect of higher
      temperature was identified for trees at higher altitudes. Increased levels of
      acidic deposition, together with geographical variables, were identified as the
      most important factors affecting climate-growth association. Tree age, tree size
      and soil characteristics also significantly modulate climate-growth
      relationships. The importance of all environmental variables on climate-growth
      relationships was suppressed by acidic deposition during periods when this was at
      a high level; growth was significantly more enhanced by spring and summer
      temperatures during these periods. Our results suggest that spruce will undergo
      significant growth reduction under the predicted climate changes, especially at
      the lower altitudes which lie outside of its natural range.

PMID- 28755601
TI  - Perceived usefulness of personal protective equipment in pesticide use predicts
      farmers' willingness to use it.
AB  - Personal protective equipment (PPE) can substantially reduce the risk exposure
      from pesticide spraying, but compliance is rather low, particularly among small
      scale farmers. In this study the connection between farmers' willingness to use
      PPE in pesticide handling and perceptions of PPE usefulness was examined through
      a survey of 341 small-scale farmers in Gorgan county of Golestan Province, Iran.
      Farmers who were not using PPE when working with pesticides were purposively
      selected to better serve the objective of the study. Multinomial logit regression
      models were employed to examine differences in farmers' willingness to use PPE in
      the future. Almost four out of ten farmers (38.1%) showed willingness to use PPE.
      However, 36.7% of the farmers showed unwillingness and 25.2% were unsure about
      using PPE. The average score of farmers' perceptions of PPE disadvantages
      (x=0.55) was significantly higher than the corresponding score of PPE advantages
      (x=0.38). Low availability and high price were considered the most important
      constraints in PPE use by the majority of farmers (75.4% and 74.8% of the
      farmers, respectively). Farmers who perceived usefulness of PPE, such as
      effectiveness, safety, and ease of use, were more willing to use PPE in the
      future. Those who perceived non-usefulness of PPE, driven by unavailability, high
      price, lack of use by neighbors or colleagues, and ignorance of PPE in extension
      trainings, were less likely to use PPE in the future. Findings revealed that
      willingness to use PPE among small-scale farmers when working with pesticides is
      strongly linked to their perception of PPE usefulness. Findings raise our
      understanding of the important role of farmers' knowledge in PPE acceptance and
      use and can motivate policy-makers to pay more attention to the role of farmers'
      perceptions and awareness in the success or failure of health and safety
      programs. It is necessary to incorporate farmers' preferences in extension
      programs to promote safety measures during working with pesticides.

PMID- 28755602
TI  - The mediator effect of personality traits on the relationship between childhood
      abuse and depressive symptoms in schizophrenia.
AB  - Previous studies indicated that personality traits have a mediator effect on the
      relationship between childhood abuse and depressive symptoms in major depressive
      disorder and nonclinical general adult subjects. In the present study, we aimed
      to test the hypothesis that personality traits mediate the relationship between
      childhood abuse and depressive symptoms in schizophrenia. We used the following
      questionnaires to evaluate 255 outpatients with schizophrenia: the Child Abuse
      and Trauma Scale, temperament and character inventory, and Patients Health
      Questionnire-9. Univariate analysis, multiple regression analysis, and structured
      equation modeling (SEM) were used to analyze the data. The relationship between
      neglect and sexual abuse and the severity of depressive symptoms was mostly
      mediated by the personality traits of high harm avoidance, low self-directedness,
      and low cooperativeness. This finding was supported by the results of stepwise
      multiple regression analysis and the acceptable fit indices of SEM. Thus, our
      results suggest that personality traits mediate the relationship between
      childhood abuse and depressive symptoms in schizophrenia. The present study and
      our previous studies also suggest that this mediator effect could occur
      independent of the presence or type of mental disorder. Clinicians should
      routinely assess childhood abuse history, personality traits, and their effects
      in schizophrenia.

PMID- 28755603
TI  - Anticholinergic use trends in 14,013 patients with schizophrenia from three
      national surveys on the use of psychotropic medications in China (2002-2012).
AB  - Our previous study demonstrated that there have been changes in the patterns of
      prescription antipsychotic use in China over the period from 2002 to 2012. The
      aim of this study was to evaluate whether time trends were present for the
      prescription of anticholinergic medications (ACMs) during the observation period.
      A total of 14,013 patients with schizophrenia treated in 45 psychiatric
      hospitals/centers nationwide were surveyed in 2002, 2006 and 2012. Basic socio
      demographic and clinical characteristics and the prescription of psychotropic
      drugs were recorded using a standardized protocol and data collection procedure.
      The frequency of ACM prescription was 25.9% in the whole sample (29.5%, 21.6%,
      and 27.4% in 2002, 2006 and 2012, respectively). In addition, different temporal
      trends were observed across age groups. Multiple logistic regression analysis of
      the entire sample showed that ACM prescriptions were predicted by females,
      outpatients, patients receiving high doses of antipsychotic medication, select
      study years, benzodiazepine users, patients displaying extrapyramidal side
      effects, as well as antipsychotic prescription patterns. Although there was more
      widespread use of second-generation antipsychotics over the past decade, the
      frequency of ACM use only slightly decreased. How to use ACM appropriately is
      still a therapeutic issue that needs to foster evidence-based prescription
      practice.

PMID- 28755604
TI  - Perceived expressed emotions in relatives of patients with severe mental illness:
      A comparative study.
AB  - There is paucity of studies on expressed emotion (EE) in families of patients
      with severe mental illness in sub-Saharan Africa. This study aimed to assess and
      compare the levels of expressed emotion (LEE) in relatives of patients with
      schizophrenia and bipolar affective disorder attending an out-patient clinic in
      Southwestern Nigeria. One hundred and forty consecutive clinic attendees with
      Mini-Plus diagnosis of schizophrenia and bipolar affective disorder and 140
      accompanying relatives were recruited. The patients and relatives were
      interviewed using a socio-demographic questionnaire. The perceived level of
      expressed emotion was assessed using the client version of the Level of Expressed
      Emotion Questionnaire (LEEQ). Although, the prevalence of high expressed emotion
      was higher among relatives of patients with schizophrenia when compared with
      relatives of patients with bipolar affective disorder (41% vs 37%), the
      difference was not statistically significant. The socio-demographic
      characteristics of the relatives of patients with these disorders were not
      significantly related to high EE. High expressed emotion is just as prevalent
      among relatives of patients with bipolar affective disorder as among relatives of
      patients with schizophrenia and clinicians should give similar attention to early
      detection of high EE and intervention in this population of patients and their
      relatives.

PMID- 28755605
TI  - Affective and cognitive theory of mind in borderline personality disorder: The
      role of comorbid depression.
AB  - Disturbed interpersonal relationships and misreading of others' intentions are
      core symptoms of borderline personality disorder (BPD). Despite these
      impairments, some studies have found an enhanced theory of mind (ToM) in BPD
      patients. Taking this into consideration, the current study attempts to further
      understand these discrepancies by separating ToM into two domains: affective and
      cognitive. Moreover, the study considered the role of comorbid symptoms of
      depression in these patients. Subjects were 21 patients with BPD, 23 patients
      with BPD and comorbid major depressive disorder (MDD), and 25 healthy controls
      (HC). ToM was measured with the Reading the Mind in the Eyes Test (RMET) and the
      Faux Pas Task, which assessed the affective and cognitive aspects of ToM,
      respectively. In addition, all participants were evaluated with the Beck
      Depression Inventory (BDI). Results showed that in both BPD groups (i.e., BPD
      without MDD and BPD with MDD) affective ToM scores were higher than in the HC
      group; however, in the cognitive ToM, the HC group performed better than the both
      BPD groups. Also, overall the BPD group with MDD had decreased ToM skills.
      Finally, BPD groups received greater scores on the BDI as compared to the HC
      group.

PMID- 28755606
TI  - Subtypes of suicide attempters based on longitudinal childhood profiles of co
      occurring depressive, anxious and aggressive behavior symptoms.
AB  - Because suicide attempts are multi-determined events, multiple pathways to
      suicidal behaviors exist. However, as a low-frequency behavior, within group
      differences in trajectories to attempts may not emerge when examined in samples
      including non-attempters. We used longitudinal latent profile analysis to
      identify subtypes specific for suicide attempters based on longitudinal
      trajectories of childhood clinical symptoms (i.e., depression, anxiety, and
      aggression measured in 2nd, 4th-7th grades) for 161 young adults (35.6% male;
      58.6% African American) who attempted suicide between ages 13-30 from a large,
      urban community-based, longitudinal prevention trial (n = 2311). Differences in
      psychiatric diagnoses, suicide attempt characteristics, criminal history and
      traumatic stress history were studied. Three subtypes emerged: those with all low
      (n = 32%), all high (n = 16%), and high depressive/anxious, but low aggressive (n
      = 52%) symptoms. Those with the highest levels of all symptoms were significantly
      more likely to report a younger age of suicide attempt, and demonstrate more
      substance abuse disorders and violent criminal histories. Prior studies have
      found that childhood symptoms of depression, anxiety and aggression are malleable
      targets; interventions directed at each reduce future risk for suicidal
      behaviors. Our findings highlight the link of childhood aggression with future
      suicidal behaviors extending this research by examining childhood symptoms of
      aggression in the context of depression and anxiety.

PMID- 28755607
TI  - A phase 2 randomised discontinuation trial of cabozantinib in patients with
      ovarian carcinoma.
AB  - BACKGROUND: Cabozantinib (XL184), an orally bioavailable inhibitor of vascular
      endothelial growth factor receptor 2 and MET, was assessed in a cohort of ovarian
      carcinoma patients as part of a phase 2 randomised discontinuation trial (RDT)
      with cohorts from nine different tumour types. PATIENTS AND METHODS: Patients
      received 100-mg cabozantinib daily. Those with stable disease (SD) per Response
      Evaluation Criteria in Solid Tumors at week 12 were randomised to cabozantinib or
      placebo. Primary end-points were objective response rate (ORR) at week 12 and
      progression-free survival (PFS) after random assignment. RESULTS: Seventy
      patients with ovarian carcinoma, 50% of whom were platinum refractory/resistant,
      were enrolled in this RDT. Median PFS from day 1 was 5.5 months for all patients.
      The ORR at week 12 was 21%; one patient achieved a complete response (CR), and 14
      patients (20%) achieved a confirmed partial response (PR). The overall disease
      control rate (CR + PR + SD) at week 12 was 50%. Throughout the study, 70% of the
      patients with >=1 postbaseline scan had tumour regression, and randomisation was
      discontinued early. For patients with SD randomised to cabozantinib, PFS was 5.9
      months after randomisation. The most common grade 3/4 adverse events were
      diarrhoea (14%), palmar-plantar erythrodysesthesia syndrome (6%), asthenia (6%),
      hypertension (6%) and neutropenia (6%). Dose reductions were required in 37% of
      the patients during the first 12 weeks. CONCLUSION: Cabozantinib demonstrates
      clinical activity, with acceptable toxicities, in patients with ovarian carcinoma
      based on ORR and regression of tumour target lesions. REGISTRATION: This trial is
      registered at ClinicalTrial.gov (NCT00940225).

PMID- 28755608
TI  - Fully disposable microfluidic electrochemical device for detection of estrogen
      receptor alpha breast cancer biomarker.
AB  - A novel fully disposable microfluidic electrochemical array device (uFED) was
      developed and successfully applied for detection of the biomarker estrogen
      receptor alpha (ERalpha). The uFED was constructed using low-cost materials and
      an inexpensive home cutter printer enabled the manufacture of dozens of uFEDs in
      less than 2h, at a cost of less than US$ 0.20 in material per device. The uFED
      incorporates counter and reference electrodes and eight carbon-based working
      electrodes, which were modified with DNA sequences known as estrogen response
      elements (DNA-ERE), where ERalpha binds specifically. Paramagnetic particles
      heavily decorated with anti-ERalpha antibody and horseradish peroxidase (MP-Ab
      HRP) were used to efficiently capture ERalpha from the sample solution. The
      ERalpha-MP-Ab-HRP bioconjugate formed was injected into the uFED and incubated
      with the DNA-ERE-modified electrodes, followed by amperometric detection with
      application of -0.2V vs. Ag|AgCl while a mixture of H2O2 and hydroquinone was
      injected into the microfluidic device. An ultralow limit of detection of 10.0 fg
      mL-1 was obtained with the proposed method. The performance of the assay, in
      terms of sensitivity and reproducibility, was studied using undiluted calf serum,
      and excellent recoveries in the range of 94.7-108% were achieved for the
      detection of ERalpha in MCF-7 cell lysate. The uFED system can be easily
      constructed and applied for multiplex biomarker detection, making the device an
      excellent cost-effective alternative for cancer diagnosis, especially in
      developing countries.

PMID- 28755609
TI  - A resettable and reprogrammable keypad lock based on electrochromic Prussian blue
      films and biocatalysis of immobilized glucose oxidase in a bipolar electrode
      system.
AB  - Herein, a resettable and reprogrammable biomolecular keypad lock on the basis of
      a closed bipolar electrode (BPE) system was established. In this system, one ITO
      electrode with immobilized chitosan (CS) and glucose oxidase (GOD), designated as
      CS-GOD, acted as one pole of BPE in the sensing cell; another ITO with
      electrodeposited Prussian blue (PB) films as the other pole in the reporting
      cell. The addition of ascorbic acid (AA) in the sensing cell with driving voltage
      (Vtot) at +2.5V would make the PB films become Prussian white (PW) in the
      reporting cell, accompanied by the color change from blue to nearly transparent.
      On the other hand, with the help of oxygen, the addition of glucose in the
      sensing cell with Vtot at -1.5V would induce PW back to PB. The change of color
      and the corresponding UV-vis absorbance at 700nm for the PB/PW films in the
      reporting cell could be reversibly switched by changing the solute in the sensing
      cell between AA and glucose and then switching Vtot between +2.5 and -1.5V. Based
      on these, a keypad lock was developed with AA, glucose and Vtot as 3 inputs, and
      the color change of the PB/PW films as the output. This keypad lock system
      combined enzymatic catalysis with bipolar electrochemistry, demonstrating some
      unique advantages such as good reprogrammability, easy resettability and visual
      readout by naked eye.

PMID- 28755610
TI  - Neutralized chimeric DNA probe for detection of single nucleotide polymorphism on
      surface plasmon resonance biosensor.
AB  - An implementation of neutralized chimeric DNA oligomer as a probe for sensitive
      detection of single nucleotide polymorphisms (SNPs) on a surface plasmon
      resonance imaging sensor is investigated. The chimeric DNA oligomer was
      synthesized in a conventional DNA synthesizer, containing neutral nucleotides
      with a methylated phosphate group. The secondary structures and melting points of
      the chimeric DNA fragment and its complexes with perfect-matched and single
      mismatched complementary DNA molecules were examined by using circular dichroism
      and UV-vis spectroscopy in comparison with the native probe DNA counterpart. The
      results indicate that the chimeric DNA complexes can form a B-form structure and
      exhibit high thermostability. Moreover, the hybridization and discrimination
      efficiency of the chimeric probe DNA for the SNP genotyping were verified by
      using the SPRi sensor under different experimental conditions. The data reveal
      the effects of the ionic strength and operation temperature on the selectivity of
      the chimeric probe DNA for the SNP detection. The hybridization condition with a
      low ionic strength and high temperature allows the chimeric probe DNA
      distinguishing perfect-matched and single-mismatched target DNA molecules to the
      best extent, likely due to the reduced electrostatic repulsive force and presence
      of the additional methyl group on the backbone. Consequently, the direct and
      label-free detection with the SPR technique and neutralized chimeric probe DNA
      can be realized for the SNP genotyping by optimizing the operation condition and
      sequence design.

PMID- 28755611
TI  - Fixed and mobile-bearing total ankle prostheses: Effect on tibial bone strain.
AB  - BACKGROUND: Total ankle replacement is associated to a high revision rate. To
      improve implant survival, the potential advantage of prostheses with fixed
      bearing compared to mobile bearing is unclear. The objective of this study was to
      test the hypothesis that fixed and mobile bearing prostheses are associated with
      different biomechanical quantities typically associated to implant failure.
      METHODS: With a validated finite element model, we compared three cases: a
      prosthesis with a fixed bearing, a prosthesis with a mobile bearing in a centered
      position, and a prosthesis with mobile bearing in an eccentric position. Both
      prostheses were obtained from the same manufacturer. They were tested on seven
      tibias with maximum axial compression force during walking. We tested the
      hypothesis that there was a difference of bone strain, bone-implant interfacial
      stress, and bone support between the three cases. We also evaluated, for the
      three cases, the correlations between bone support, bone strain and bone-implant
      interfacial stress. FINDINGS: There were no statistically significant differences
      between the three cases. Overall, bone support was mainly trabecular, and less
      effective in the posterior side. Bone strain and bone-implant interfacial stress
      were strongly correlated to bone support. INTERPRETATIONS: Even if slight
      differences are observed between fixed and mobile bearing, it is not enough to
      put forward the superiority of one of these implants regarding their reaction to
      axial compression. When associated to the published clinical results, our study
      provides no argument to warn surgeons against the use of two-components fixed
      bearing implants.

PMID- 28755612
TI  - "We definitely are role models": Exploring how clinical instructors' influence
      nursing students' attitudes towards older adults.
AB  - The world's population is getting older, which will inevitably cause increased
      demands for nurses to provide high quality care to this demographic. Attitudes
      have been shown to influence the quality of care that older adults receive. It is
      therefore important to gain a better understanding of what influences nursing
      students' attitudes towards older adults. This article reports on one of three
      inter-connected research questions of a mixed methods study that explored the
      relationship between clinical instructors' attitudes and nursing students'
      attitudes towards older adults. Semi-structured interviews were conducted with 6
      clinical instructors and 13 nursing students. Interview data was analyzed using
      thematic analysis. A conceptual model was developed from the research findings,
      which revealed that nursing instructors are seen as strong role models for their
      students, and as role models, they influence students through demonstrations,
      expectations and support. As a result, nursing students mirror the attitudes of
      their instructors towards older adults. Findings from this study highlight the
      strong connection between nursing instructors' and students' attitudes. This has
      important implications for nursing education including strategies that
      instructors can employ to enhance students' attitudes towards older adults.
      Insights from this study also have the potential to improve the quality of care
      that future nurses provide to older adults.

PMID- 28755613
TI  - DSM-5 cannabis use disorder in the National Epidemiologic Survey on Alcohol and
      Related Conditions-III: Gender-specific profiles.
AB  - OBJECTIVE: The objective of this study was to present current information on the
      prevalence, correlates, comorbidity and quality of life among men and women with
      cannabis use disorder (CUD). METHODS: In 2012-2013, 36,309 respondents >=18years
      old participated in face-to-face interviews in the National Epidemiologic Survey
      on Alcohol and Related Conditions-III. RESULTS: Prevalence of 12-month CUD was
      greater among men (3.5%) than women (1.7%). Women experienced shorter duration
      from onset of cannabis use to onset of CUD than men (mean=5.8years, men;
      mean=4.7years, women). In both men and women, prevalences of CUD were greater
      among young adults, Blacks, and those with lower income and greater among Native
      American women relative to White women. CUD was highly comorbid with other
      substance use disorders, PTSD, ASPD and borderline and schizotypal PDs for men
      and women. Quality of life for individuals with CUD was low regardless of gender.
      CONCLUSIONS: DSM-5 CUD among men and women is highly prevalent, comorbid and
      characterized by low quality of life. Results highlighted the need for integrated
      treatment of CUD and comorbid disorders and the urgency of identifying and
      implementing effective prevention and intervention approaches, especially for
      those sociodemographic subgroups for which both men and women are at greater risk
      for the disorder.

PMID- 28755614
TI  - Immediate emergency free anterolateral thigh flap after car-tyre friction injury:
      A case report with eight years follow-up.
AB  - The car-tyre friction injury has differences from other injuries. The components
      of injury which are burn, crushing, shearing, and degloving occur. Many treatment
      options can be performed for coverage of wound which are Vacuum Assisted Closure
      system (V.A.C), skin grafting, free flaps, local flaps and cross leg flap.

PMID- 28755615
TI  - Abdominal leiomyosarcomatosis after surgery with external morcellation for occult
      smooth muscle tumors of uncertain malignant potential: A case report.
AB  - INTRODUCTION: Although rare, cases of abdominal sarcomatosis (AS) after
      laparotomy/laparoscopic interventions for uterine smooth muscle tumors of
      uncertain malignant potential (STUMP) have been reported. PRESENTATION OF CASE:
      We describe a rare case of diffuse abdominal sarcomatosis in a patient that some
      year earlier had undergone myomectomy for a suspected uterine myoma, which was
      histologically proven to be a STUMP. Once the patient was admitted at our
      Department, she underwent a diagnostic laparoscopy that confirmed a condition of
      peritoneal sarcomatosis disseminated through the entire abdomen, and then a
      laparotomic total hysterectomy, bilateral salpingo-oophorectomy, and total
      omentectomy, achieving a complete cytoreduction. Histological examination showed
      high-grade uterine leyomiosarcoma (LMS). Since there is no evidence of any
      clinical benefit of adjuvant treatment, given the risk of disease recurrence, we
      decided, with the patient's agreement, to conduct close follow-up with a Positron
      Emission Tomography (PET)/Computed Tomography (CT) scan every 3months and
      diagnostic laparoscopy every 6months, even in the absence of PET/CT positivity.
      After 2years PET/CT showed a relapse of LMS in the perigastric region and,
      therefore the patient underwent a diagnostic/operative laparoscopy with complete
      removal of the neoplastic recurrence. To date, the patient is disease-free.
      DISCUSSION AND CONCLUSION: STUMPs should be submitted to a frequent surveillance
      for their risk of recurrence, dissemination and transformation into LMS, even
      many years after the first diagnosis. A follow-up including surgical re
      exploration with laparoscopy and PET/CT imaging may allow early detection and
      timely treatment of the relapse with good long-term outcome, as demonstrated by
      our case.

PMID- 28755616
TI  - Endotracheal hamartoma case report: Two contrasting clinical presentations of a
      rare entity.
AB  - INTRODUCTION: The majority of tracheal tumors in adults are malignant. The
      finding of a benign tumor in the trachea is uncommon and endotracheal hamartomas
      are rare. PRESENTATION OF CASE: We report two cases presenting within six months
      at our institution. The first patient is a 67 year-old man who was found to have
      an asymptomatic endotracheal hamartoma on chest imaging for aortic valve
      replacement. The second patient is a 46 year-old man with an extensive continued
      tobacco use disorder and a known endotracheal lesion identified 8 years prior to
      intervention. Both patients were treated surgically and recovered without
      complications. DISCUSSION: Identification of these lesions and timely management
      are necessary because without intervention, they can lead to fatal complications.
      Most symptoms of tracheal hamartoma result from mechanical obstruction with the
      earliest presenting symptom being dyspnea, but as evident in these two cases,
      they can have different presentations. CONCLUSION: We have found that
      endotracheal hamartoma has a tendency to present in Caucasian, male patients with
      a comorbidity of respiratory disease and variable smoking history, but it can
      also present in asymptomatic patients with no significant smoking history.

PMID- 28755617
TI  - Effects of additional data on Bayesian clustering.
AB  - Hierarchical probabilistic models, such as mixture models, are used for cluster
      analysis. These models have two types of variables: observable and latent. In
      cluster analysis, the latent variable is estimated, and it is expected that
      additional information will improve the accuracy of the estimation of the latent
      variable. Many proposed learning methods are able to use additional data; these
      include semi-supervised learning and transfer learning. However, from a
      statistical point of view, a complex probabilistic model that encompasses both
      the initial and additional data might be less accurate due to having a higher
      dimensional parameter. The present paper presents a theoretical analysis of the
      accuracy of such a model and clarifies which factor has the greatest effect on
      its accuracy, the advantages of obtaining additional data, and the disadvantages
      of increasing the complexity.

PMID- 28755618
TI  - Limitations of shallow nets approximation.
AB  - In this paper, we aim at analyzing the approximation abilities of shallow
      networks in reproducing kernel Hilbert spaces (RKHSs). We prove that there is a
      probability measure such that the achievable lower bound for approximating by
      shallow nets can be realized for all functions in balls of reproducing kernel
      Hilbert space with high probability, which is different with the classical
      minimax approximation error estimates. This result together with the existing
      approximation results for deep nets shows the limitations for shallow nets and
      provides a theoretical explanation on why deep nets perform better than shallow
      nets.

PMID- 28755619
TI  - Applicability of the APACHE II model to a lower middle income country.
AB  - PURPOSE: To determine the utility of APACHE II in a low-and middle-income (LMIC)
      setting and the implications of missing data. MATERIALS AND METHODS: Patients
      meeting APACHE II inclusion criteria admitted to 18 ICUs in Sri Lanka over three
      consecutive months had data necessary for the calculation of APACHE II,
      probabilities prospectively extracted from case notes. APACHE II physiology score
      (APS), probabilities, Standardised (ICU) Mortality Ratio (SMR), discrimination
      (AUROC), and calibration (C-statistic) were calculated, both by imputing missing
      measurements with normal values and by Multiple Imputation using Chained
      Equations (MICE). RESULTS: From a total of 995 patients admitted during the study
      period, 736 had APACHE II probabilities calculated. Data availability for APS
      calculation ranged from 70.6% to 88.4% for bedside observations and 18.7% to
      63.4% for invasive measurements. SMR (95% CI) was 1.27 (1.17, 1.40) and 0.46
      (0.44, 0.49), AUROC (95% CI) was 0.70 (0.65, 0.76) and 0.74 (0.68, 0.80), and C
      statistic was 68.8 and 156.6 for normal value imputation and MICE, respectively.
      CONCLUSIONS: An incomplete dataset confounds interpretation of prognostic model
      performance in LMICs, wherein imputation using normal values is not a suitable
      strategy. Improving data availability, researching imputation methods and
      developing setting-adapted and simpler prognostic models are warranted.

PMID- 28755620
TI  - Does the increasing placebo response impact outcomes of adult and pediatric ADHD
      clinical trials? Data from the US Food and Drug Administration 2000-2009.
AB  - In a study of recent antidepressant clinical trial data, it was found placebo
      response had grown significantly over time and that contrary to expectations,
      trial outcome measures and success rate were not impacted. The aim of this paper
      was to evaluate if this trend of increasing placebo response and stable outcome
      measures could be seen in clinical trial data for Attention-Deficit Hyperactivity
      Disorder, a different psychiatric condition with susceptibility to placebo
      response. For this reason, we evaluated efficacy data reported in the FDA Medical
      and Statistical reviews for 10 ADHD medication programs (4917 patients, 17
      trials, 29 treatment arms). Placebo and medication response were measured as
      percent symptom reduction and effect sizes and drug-placebo differences were
      calculated for each treatment arm and analyzed in relation to year of approval.
      We also investigated the potential role of age and medication class on trends and
      outcomes. Results showed a similar pattern to antidepressants wherein the placebo
      response is rising significantly over time (r = 0.636, p = 0.006) and effect size
      (r < 0.0001, p = 1.0), drug-placebo difference (r = -0.238, p = 0.214), and
      success rate (28/29 97%) have remained unaffected, likely due to a parallel,
      although not statistically significant increase in medication response (r =
      0.326, p = 0.085). Age and medication class did not alter these observed time
      trends but pediatric trials and stimulants were found to have more robust
      treatment effects than adult trials and non-stimulants. The results of this study
      suggest that like antidepressants, the relationship between placebo response and
      the outcomes of ADHD clinical trials is weak at best.

PMID- 28755621
TI  - Prognostic assessment and systemic treatments of invasive local relapses of
      hormone receptor-positive breast cancer.
AB  - The rate of local recurrences, after breast-conserving surgery or mastectomy for
      hormone receptor-positive (HR+) breast cancer, has dramatically changed in last
      decades, due to advances in surgical and radiation techniques and a more
      extensive use of adjuvant systemic treatments. However, the occurrence of local
      recurrences remains a major predictor for distant metastasis and is responsible
      for increased cancer-specific death. It has been estimated that 1 in 4 HR+ and HR
      ipsilateral breast recurrences leads to widespread metastatic disease, with an
      annual mortality rate of 10% in the first 5 years. Nevertheless, very few studies
      have been conducted to evaluate the optimal care of purely HR+ local relapses of
      breast cancer, after surgical removal. In this review we have highlighted the
      available knowledge on prognostic assessment and systemic treatment for women
      experiencing local relapses of HR+ breast cancers, underlying unsolved questions
      and controversial clinical aspects.

PMID- 28755622
TI  - Trajectories of suicidal ideation over 6 months among 482 outpatients with
      bipolar disorder.
AB  - INTRODUCTION: Suicidal ideation occurs frequently among individuals with bipolar
      disorder; however, its course and persistence over time remains unclear. We aimed
      to investigate 6-months trajectories of suicidal ideation among adults with
      bipolar disorder. METHODS: The Bipolar CHOICE study randomized 482 outpatients
      with bipolar disorder to 6 months of lithium- or quetiapine-based treatment
      including other psychotropic medications as clinically indicated. Participants
      were asked at 9 visits about suicidal ideation using the Concise Health Risk
      Tracking scale. We performed latent Growth Mixture Modelling analysis to
      empirically identify trajectories of suicidal ideation. Multinomial logistic
      regression analyses were applied to estimate associations between trajectories
      and potential predictors. RESULTS: We identified four distinct trajectories. The
      Moderate-Stable group represented 11.1% and was characterized by constant
      suicidal ideation. The Moderate-Unstable group included 2.9% with persistent
      thoughts about suicide with a more fluctuating course. The third (Persistent-low,
      20.8%) and fourth group (Persistent-very-low, 65.1%) were characterized by low
      levels of suicidal ideation. Higher depression scores and previous suicide
      attempts (non-significant trend) predicted membership of the Moderate-Stable
      group, whereas randomized treatment did not. LIMITATIONS: No specific treatments
      against suicidal ideation were included and suicidal thoughts may persist for
      several years. CONCLUSION: More than one in ten adult outpatients with bipolar
      disorder had moderately increased suicidal ideation throughout 6 months of
      pharmacotherapy. The identified predictors may help clinicians to identify those
      with additional need for treatment against suicidal thoughts and future studies
      need to investigate whether targeted treatment (pharmacological and non
      pharmacological) may improve the course of persistent suicidal ideation.

PMID- 28755623
TI  - The presence of anxiety, depression and stress in women and their partners during
      pregnancies following perinatal loss: A meta-analysis.
AB  - BACKGROUND: Research indicates perinatal loss is associated with anxiety,
      depression and stress in women and partners during subsequent pregnancies.
      However, there are no robust estimates of anxiety, depression and stress for this
      group. We meta-analytically estimated rates of anxiety, depression and stress in
      pregnant women and their partners during pregnancies after previous perinatal
      loss. METHODS: Databases (Medline, PsychInfo, Embase, Cinahl Plus) and grey
      literature were searched from 1995 through to May 2016. Search terms included:
      depression, anxiety, or stress with perinatal loss (miscarry*, perinatal death,
      spontaneous abortion, fetal death, stillbirth, intrauterine death, TOPFA) and
      subsequent pregnancy. Case-controlled, English-language studies using validated
      measures of anxiety, depression or stress in women or partners during pregnancy
      following perinatal loss were included. Data for effect sizes, study and
      demographic data were extracted. RESULTS: We identified nineteen studies
      representing n = 5114 women with previous loss; n = 30,272 controls; n = 106
      partners with previous perinatal loss; and n = 91 control men. Random effects
      modelling demonstrated significant effects of perinatal loss on anxiety (d =
      0.69, 95% CI = 0.41-0.97) and depression (d = 0.22, 95% CI = 0.15-0.30) in women;
      but no effect on stress (d = - 0.002, 95% CI = - 0.0639 to 0.0605). LIMITATIONS:
      This study was limited by the quality of available studies, underpowered
      moderator analyses and an inability to examine additional covariates.
      Insufficient data were available to generate reliable effects for psychological
      distress in partners. CONCLUSIONS: Our findings confirm elevated anxiety and
      depression levels during pregnancies following perinatal loss. Further research
      on predictors of distress in women and their partners is required.

PMID- 28755624
TI  - The relationship between therapeutic alliance and patient's suicidal thoughts,
      self-harming behaviours and suicide attempts: A systematic review.
AB  - BACKGROUND: Suicidality is a common concern for people with mental health
      problems. The interpersonal nature of suicidality suggests that therapeutic
      alliance may be important when working clinically with suicidal patients. This
      paper is a systematic review of studies investigating the association between
      alliance and treatment outcome relating to suicidal ideation and behaviours.
      METHODS: Systematic searches of PsychINFO, MEDLINE, AMED, EMBASE, Web of Science
      and CINAHL were completed using words that captured the concepts of alliance and
      suicidality. Eligible studies: involved participants aged 18-years-old or over;
      used a validated measure of therapeutic alliance; and reported associations
      between alliance and suicidality. Abstracts, qualitative studies and articles not
      written in English were excluded. RESULTS: Twelve studies were included. Findings
      indicated that alliance is associated with suicidality. Alliance was related to
      suicidality in eleven of the papers. Self-harming behaviours had the strongest
      association with patient-rated alliance. Suicide attempts had the weakest
      association, possibly due to the infrequency of suicide attempts in the studies
      reviewed. LIMITATIONS: The twelve studies were heterogeneous in terms of the
      measure of alliance used, method of assessing suicidality, clinical setting and
      professional-type. This variability limited the degree to which findings could be
      synthesised. CONCLUSION: Therapists, care-coordinators and mental health teams
      should recognise the importance of building a strong therapeutic alliance with
      suicidal patients. Researchers should use consistent methods of measuring
      alliance and assessing suicidality in future studies. Clinicians and researchers
      should note that suicidal thoughts, self-harm and suicide attempts may be related
      to alliance in different ways and therefore should be assessed as separate
      constructs.

PMID- 28755625
TI  - X-ray irradiation has positive effects for the recovery of peripheral nerve
      injury maybe through the vascular smooth muscle contraction signaling pathway.
AB  - INTRODUCTION: It is well known that moderate to high doses of ionizing radiation
      have a toxic effect on the organism. However, there are few experimental studies
      on the mechanisms of LDR ionizing radiation on nerve regeneration after
      peripheral nerve injury. METHODS: We established the rats' peripheral nerve
      injury model via repaired Peripheral nerve injury nerve, vascular endothelial
      growth factor a and Growth associated protein-43 were detected from different
      treatment groups. We performed transcriptome sequencing focusing on investigating
      the differentially expressed genes and gene functions between the control group
      and 1Gy group. Sequencing was done by using high-throughput RNA-sequencing (RNA
      seq) technologies. RESULTS: The results showed the 1Gy group to be the most
      effective promoting repair. RNA-sequencing identified 619 differently expressed
      genes between control and treated groups. A Gene Ontology analysis of the
      differentially expressed genes revealed enrichment in the functional pathways.
      Among them, candidate genes associated with nerve repair were identified.
      DISCUSSION: Pathways involved in cell-substrate adhesion, vascular smooth muscle
      contraction and cell adhesion molecule signaling may be involved in recovery from
      peripheral nerve injury.

PMID- 28755626
TI  - The use of forensic DNA analysis in humanitarian forensic action: The development
      of a set of international standards.
AB  - DNA analysis was first applied to the identification of victims of armed
      conflicts and other situations of violence (ACOSV) in the mid-1990s, starting in
      South America and the Balkans. Argentina was the first country to establish a
      genetic database specifically developed to identify disappeared children.
      Following on from these programs the early 2000s marked major programs, using a
      largely DNA-led approach, identifying missing persons in the Balkans and
      following the attack on the World Trade Center in New York. These two
      identification programs significantly expanded the magnitude of events to which
      DNA analysis was used to help provide the identity of missing persons. Guidelines
      developed by Interpol (2014) [1] related to best practice for identification of
      human remains following DVI type scenarios have been widely disseminated around
      the forensic community; in numerous cases these guidelines have been adopted or
      incorporated into national guidelines/standards/practice. However, given the
      complexity of many humanitarian contexts in which forensic science is employed
      there is a lack of internationally accepted guidelines, related to these
      contexts, for authorities to reference. In response the Argentine government's
      Human Rights Division in the Ministry of Foreign Affairs and Worship (MREC)
      proposed that the United Nations (UN) should promote best practice in the use of
      forensic genetics in humanitarian forensic action: this was adopted by the UN in
      Resolutions A/HRC/RES/10/26 and A/HRC/RES/15/5. Following on from the adoption of
      the resolutions MREC has coordinated, with the support of the International
      Committee of the Red Cross (ICRC), the drafting of a set of guidelines (MREC,
      ICRC, 2014) [2], with input from national and international agencies. To date the
      guidelines have been presented to South America's MERCOSUR and the UN and have
      been disseminated to interested parties.

PMID- 28755627
TI  - The importance of laboratory re-evaluation in cases of suspected child abuse - A
      case report.
AB  - In order to accurately diagnose child abuse or neglect, a physician needs to be
      familiar with diseases and medical conditions that can simulate maltreatment.
      Unrecognized cases of abuse may lead to insufficient child protection, whereas,
      on the other hand, over-diagnosis could be the cause of various problems for the
      family and their potentially accused members. Regarding child abuse, numerous
      cases of false diagnoses with undetected causes of bleeding are described in the
      scientific literature, but, specifically concerning leukemia in childhood, only
      very few case reports exist. Here, for the first time, we report a case of a 2
      year-old boy who got hospitalized twice because of suspicious injuries and
      psychosocial conspicuities, in a family situation known for repeated endangerment
      of the child's well-being. After his first hospitalization with injuries typical
      for child abuse, but without paraclinical abnormalities, medical inspections were
      arranged periodically. The child was hospitalized with signs of repeated child
      abuse again five months later. During second admission, an acute lymphoblastic
      leukemia was revealed by intermittent laboratory examination, ordered due to new
      bruises with changes in morphology, identifiable as petechial hemorrhages. This
      case elucidates the discussion of known cases of leukemia in childhood associated
      with suspected child abuse in order to provide an overview of possible diseases
      mimicking maltreatment. To arrange necessary supportive examinations, a skillful
      interaction between pediatrician and forensic pathologist is crucial in the
      differentiation between accidental and non-accidental injury.

PMID- 28755628
TI  - Iatrogenic acquired factor V inhibitors: A case report and review of the French
      pharmacovigilance database.

PMID- 28755629
TI  - Abscisic acid treatment alleviates cadmium toxicity in purple flowering stalk
      (Brassica campestris L. ssp. chinensis var. purpurea Hort.) seedlings.
AB  - The aim of this research was to investigate how exogenous abscisic acid (ABA)
      alleviates cadmium (Cd) toxicity in purple flowering stalk (Brassica campestris
      L. ssp. chinensis) and evaluate whether it could be a potential choice for
      phytoremediation. Purple flowering stalk seedlings were cultivated in a
      hydroponic system with Cd at various concentrations (0-100 MUmol L-1) as controls
      and Cd plus ABA as the treatment in the growth media. The soluble proteins,
      chlorophyll contents and the activity of the antioxidant enzyme system were
      determined by previously established biochemical methods. The contents of soluble
      protein and chlorophyll, and the activities of superoxide dismutase (SOD, EC 1.
      15.1.1), peroxidase (POD, EC 1.11.1.7), ascorbic peroxidase (APX, EC 1.11.1.11),
      glutathione reductase (GR, EC 1.8.1.7) and superoxide anion (O2.-) increased with
      the increase of external Cd concentrations, and then decreased in both Cd and
      Cd+ABA treatments, with higher activities of enzymes but lower level of O2.- in
      Cd+ABA than those in Cdonly treatments. It indicated that a stress adaptation
      mechanism was employed at lower Cd concentrations. The contents of
      malondialdehyde (MDA) and hydrogen peroxide (H2O2), increased with the increase
      of Cd concentrations in the growth medium, with the highest levels in the
      treatment of 100 MUmol L-1 Cd with lower levels in respective Cd+ABAtreatments
      than the Cd only treatmetns. Plants treated with 100 MUmol L-1 Cd plus ABA showed
      a 60% decrease in Cd content in the leaves but a 259% increase in Cd content in
      the roots. In summary, exogenous ABA might alleviate Cd toxicity in purple
      flowering stalk mainly by reducing the reactive oxygen species (ROS) though
      activing the antioxidant enzyme system and accumulating more Cd in roots.

PMID- 28755630
TI  - The Arabic Version of The Depression Anxiety Stress Scale-21: Cumulative scaling
      and discriminant-validation testing.
AB  - OBJECTIVE: This study aimed to examine the validity of the Arabic version of the
      Depression Anxiety Stress Scale-21 (DASS-21) in 149 illicit drug users. METHODS:
      We calculated alpha coefficient, inter-item and item-total correlations,
      coefficients of reproducibility and scalability (CR and CS), item difficulty and
      discrimination indices. RESULTS: The DASS-21 had an acceptable reliability; but
      values of the CR and the CS were less than acceptable. Items varied in difficulty
      and discrimination; some items are candidates for elimination. CONCLUSION: The
      DASS-21 is a probabilistic and not a deterministic measure of distress; it has
      problematic items and needs further investigations.

PMID- 28755631
TI  - Upregulation of UCP2 in beta-cells confers partial protection against both
      oxidative stress and glucotoxicity.
AB  - Deterioration of pancreatic beta-cells plays a critical role in the development
      of type 2 diabetes. Among the various stressors contributing to these deleterious
      effects, glucotoxicity and superoxides have been proposed as major players. In
      this context, the mitochondrial uncoupling protein UCP2 is regularly associated
      with the stress response. In the present study, we tested the effects of UCP2
      upregulation in mouse islets with beta-cell specific overexpression of UCP2 (RIP
      UCP2). Islets were subjected to both chronic glucotoxicity (7 days at 30mM
      glucose) and acute oxidative stress (200uM H2O2 for 10min). Increased UCP2
      expression did not alter mitochondrial potential and ATP generation but protected
      against glucotoxic effects. Glucose-stimulated insulin secretion was altered by
      both glucotoxicity and oxidative stress, in particular through higher basal
      insulin release at non-stimulatory glucose concentrations. The secretory response
      to glucose stimulation was partially preserved in beta-cells overexpressing UCP2.
      The higher rate of cell death induced by chronic high glucose exposure was lower
      in RIP-UCP2 islets. Finally, superoxide production was reduced by high glucose,
      both under acute and chronic conditions, and not modified by UCP2 overexpression.
      In conclusion, upregulation of UCP2 conferred protective effects to the stressed
      beta-cell through mechanisms not directly associated with superoxide production.

PMID- 28755633
TI  - Embryotoxic effects of dissolved okadaic acid on the development of Longfin
      yellowtail Seriola rivoliana.
AB  - In the context of global climate change where harmful algal blooms (HABs) might
      become more frequent and more severe, several studies have been conducted on the
      perturbation of embryonic development of marine animals by microalgal toxins.
      Okadaic acid (OA) and analogs (DSP toxins) produced by dinoflagellates of the
      genera Dynophysis and Prorocentrum are known to disturb embryogenesis. This study
      investigated the impact of dissolved DSP toxin (OA and Dinophysistoxin 1, DTX-1)
      exposure on embryo development of Longfin yellowtail Seriola rivoliana. Eggs were
      exposed to different concentrations of dissolved DSP toxins (low treatment: at
      120MUgl-1 OA eq; high treatment 175MUgl-1 OA eq.). The first objective was to
      study the global toxic effect of DSP toxins with hatching percentages. Secondly,
      the effect of these toxins was investigated at molecular and functional level by
      measuring expression of responsible genes for bone morphogenetic protein (BMP)
      and proliferating cell nuclear antigen (PCNA) measuring phosphatase enzyme
      (serine/threonine and alkaline phosphatases) activities. Our results showed
      drastic mortalities induced by DSP toxins in both low and high concentration
      treatments. Activities of both protein and alkaline phosphatases were
      significantly inhibited by DSP toxin treatments, whose effects on gene expression
      were less evident, but levels of BMP expression in eggs treated with the lowest
      toxin concentration were significantly different from that in the control
      treatment. This work revealed an embryotoxic effect of DSP toxins resulting in
      high mortality of eggs. Phosphatase inhibition could have participated in part in
      these global effects by perturbing the regulation of pathways related to
      embryogenesis and resulting in a perturbation of gene expression.

PMID- 28755634
TI  - Validation study of a new method for sexual prediction based on CBCT analysis of
      maxillary sinus and mandibular canal.
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of two craniometric
      methods for sexual prediction (SP) using cone-beam computed tomography (CBCT) in
      the Dutch population and to construct a formula for each method and then the two
      combined. DESIGN: One-hundred sixty CBCT images were selected from a Dutch
      database (80 males and 80 females). The images were analyzed by two examiners
      taking seven measurements in the maxillary sinus (MS) region (first method) and
      nine in the mandibular canal (MC) region (second method). The most predictive
      measurements in both methods were used to develop an equation to determine the
      accuracy of each method. RESULTS: All measurements showed statistical difference
      between genders. Logistic regression results showed two variables with greater SP
      index with 75% accuracy in the first method and four variables with 71.9%
      accuracy in the second. The two methods combined showed another four variables
      with 78.5% accuracy. CONCLUSION: All measurements showed statistically
      significant differences between sexes. The SP accuracy values were 75% for first
      71.9% for the second method. When the two methods were combined, the accuracy
      increased to 78.5%. The formulas developed in this study can be applied as a
      complementary method for human identification in the Dutch population.

PMID- 28755632
TI  - Heightened activity in social reward networks is associated with adolescents'
      risky sexual behaviors.
AB  - Adolescent sexual risk behavior can lead to serious health consequences, yet few
      investigations have addressed its neurodevelopmental mechanisms. Social
      neurocircuitry is postulated to underlie the development of risky sexual
      behavior, and response to social reward may be especially relevant. Typically
      developing adolescents (N=47; 18M, 29F; 16.3+/-1.4years; 42.5% sexual intercourse
      experience) completed a social reward fMRI task and reported their sexual risk
      behaviors (e.g., lifetime sexual partners) on the Youth Risk Behavior Survey
      (YRBS). Neural response and functional connectivity to social reward were
      compared for adolescents with higher- and lower-risk sexual behavior. Adolescents
      with higher-risk sexual behaviors demonstrated increased activation in the right
      precuneus and the right temporoparietal junction during receipt of social reward.
      Adolescents with higher-risk sexual behaviors also demonstrated greater
      functional connectivity between the precuneus and the temporoparietal junction
      bilaterally, dorsal medial prefrontal cortex, and left anterior
      insula/ventrolateral prefrontal cortex. The greater activation and functional
      connectivity in self-referential, social reward, and affective processing regions
      among higher sexual risk adolescents underscores the importance of social
      influence underlying sexual risk behaviors. Furthermore, results suggest an
      orientation towards and sensitivity to social rewards among youth engaging in
      higher-risk sexual behavior, perhaps as a consequence of or vulnerability to such
      behavior.

PMID- 28755635
TI  - Structure-based design, synthesis, and evaluation of 4,5,6,7-tetrahydro-1H
      pyrazolo[4,3-c]pyridine derivatives as novel c-Met inhibitors.
AB  - c-Met was emerging as an attractive target for cancer-targeted therapy because
      deregulation of c-Met has been observed in multiple tumor types. A series of
      4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine derivatives were designed,
      synthesized and evaluated for their enzymatic inhibitory activity against c-Met
      kinase and cellular potency against MKN45, EBC-1 and PC-3 cell lines. Nine of
      them showed better activity than lead compound 1 which was found via computer
      aided drug design. Among them, compound 8c showed inhibitory activity of 68 nM
      against c-Met and low micromole cellular potency against MKN45 and EBC-1 cell
      lines. Moreover, 8c demonstrated more than 50-fold selectivity against other
      tyrosine kinases tested. The result of western blot indicated that compound 8c
      was capable of inhibiting the phosphorylation of c-Met kinase in MKN45 cell line
      in a dose-dependent manner.

PMID- 28755636
TI  - One-pot three steps cascade synthesis of novel isoandrographolide analogues and
      their cytotoxic activity.
AB  - An efficient one-pot synthesis of novel andrographolide analogues is reported
      from a naturally occurring and abundant andrographolide isolated from aerial
      parts of Andrographis paniculata. Reactions in the one-pot proceed through a
      cascade epoxide ring opening by aniline derivatives/intramolecular ring closing
      and oxa-conjugate addition-elimination reactions. This methodology produces a new
      series of 17-amino-8-epi-isoandrographolide analogues in fair to excellent yields
      with high stereoselectivity using an economic and environmental procedure without
      base or catalyst at room temperature. Twenty-five analogues were obtained and
      cytotoxicity of all new analogues were evaluated against six cancer cell lines to
      search for a new lead compound based on andrographolide structure.

PMID- 28755637
TI  - Construction of a ratiometric fluorescent probe with an extremely large emission
      shift for imaging hypochlorite in living cells.
AB  - Hypochlorite is one of the important reactive oxygen species (ROS) and plays
      critical roles in many biologically vital processes. Herein, we present a unique
      ratiometric fluorescent probe (CBP) with an extremely large emission shift for
      detecting hypochlorite in living cells. Utilizing positively charged alpha,beta
      unsaturated carbonyl group as the reaction site, the probe CBP itself exhibited
      near-infrared (NIR) fluorescence at 662nm, and can display strong blue
      fluorescence at 456nm when responded to hypochlorite. Notably, the extremely
      large emission shift of 206nm could enable the precise measurement of the
      fluorescence peak intensities and ratios. CBP showed high sensitivity, excellent
      selectivity, desirable performance at physiological pH, and low cytotoxicity. The
      bioimaging experiments demonstrate the biological application of CBP for the
      ratiometric imaging of hypochlorite in living cells.

PMID- 28755638
TI  - Synthesis, vibrational spectrometry and thermal characterizations of coordination
      polymers derived from divalent metal ions and hydroxyl terminated polyurethane as
      ligand.
AB  - A series of novel coordination polyurethanes [HTPU-M, where M=Mn(II) 'd5', Ni(II)
      'd8', and Zn(II) 'd10'] have been synthesized to investigate the effect of
      divalent metal ions coordination on structure, thermal and adsorption properties
      of low molecular weight hydroxyl terminated polyurethane (HTPU). HTPU-M have been
      synthesized in situ where, OH group of HTPU (synthesized by the condensation
      polymerization reaction of ethylene glycol (EG) and toluene diisocyanate (TDI) in
      presence of catalyst) on condensation polymerization with metal acetate in
      presence of acid catalyst synthesized HTPU-M followed by coordination of metal
      ions with hetero atoms. The structure, composition and geometry of HTPU-M have
      been confirmed by vibrational spectrometry (FTIR), 1H NMR, elemental analysis and
      UV-Visible spectroscopy. Morphological structures of HTPU-M were analyzed by X
      Ray Diffraction analysis (XRD), Field Emission Scanning Electron Microscope (FE
      SEM) with Energy Dispersive X-ray spectroscopy (EDX) and High Resolution
      Transmission Electron Microscope (HR-TEM) techniques. The thermal degradation
      pattern and thermal stability of HTPU-M in comparison to HTPU was investigated by
      thermal-gravimetric (TG)/differential thermal (DT), analyses along with Integral
      procedure decomposition temperature (IPDT) by Doyle method. The molecular weight
      of HTPU was determined by gel permeation chromatography (GPC). The preliminary
      adsorption/desorption studies of HTPU-M for Congo red (CR) was studied by batch
      adsorption techniques. The results indicated that HTPU-M have amorphous, layered
      morphology with higher number of nano-sized grooves in comparison to HTPU.
      Coordination of metal to HTPU plays a key role in enhancing the thermal stability
      [HTPU-Ni(II)>HTPU-Mn(II)>HTPU-Zn(II)>HTPU]. The HTPU-M can be utilized for
      industrial waste water treatment by removing environmental pollutants.

PMID- 28755639
TI  - A simple, reversible, colorimetric and water-soluble fluorescent chemosensor for
      the naked-eye detection of Cu2+ in ~100% aqueous media and application to real
      samples.
AB  - A simple, reversible, colorimetric and water-soluble fluorescent chemosensor ADA
      for the naked-eye detection of Cu2+ was developed. Sensor ADA showed high
      selectivity and sensitivity toward Cu2+ in ~100% aqueous media over wide pH
      range. Sensor ADA exhibited a red-shift in the absorption spectra from 466 to
      480nm that is accompanied by significant color change from light yellow to
      yellowish brown instantaneously. The Cu2+ recognition is based on the chelation
      enhanced fluorescence quenching (CHEQ) effect of the paramagnetic nature. The
      lowest detection limit is determined to be 15.8nM, which is much lower than the
      allowable level of Cu2+ in drinking water set by U.S. Environmental Protection
      Agency (~20MUM) and the World Health Organization (~30MUM). The 1:1 binding
      process was confirmed by fluorescence measurements, IR analysis and DFT studies.
      Moreover, sensor ADA was successfully applied for determination of trace level of
      Cu2+ with 4 reuse cycles in various water samples, which affords promising
      potential in ion-detection field.

PMID- 28755640
TI  - The role of carbon chain length in the attachment between microbubbles and
      aqueous solutions of ionic liquid.
AB  - HYPOTHESIS: The effects of varying carbon chain lengths (CCLs) and concentrations
      of aqueous solutions of imidazolium based ionic liquids on bubble particle
      attachment (BPA) will provide a better understanding in catering for the varying
      degrees of surface activities in the application of the flotation technology. The
      general trends of this study should also be applicable to homologous series of
      other cationic surfactants and ionic liquids. EXPERIMENTS: Zeta potentials of
      small air bubbles and bunker oil drops dispersed in aqueous solutions of n
      methylimidazolium chloride ionic liquids (n=0, 2, 3, 6, 8, 10, 12) of
      concentrations ranging from 1000PPM to 8000PPM, as were interfacial tensions of
      these solutions with bunker oil (180cst) and contact angles made by air bubbles
      at interfaces between these solutions and thin layers of bunker oil on flat solid
      surfaces were investigated. Finally, interparticle forces analysis using the
      Derjaguin-Landau, Verwey-Overbeek (DLVO) theory is also included. FINDINGS:
      Analysis using the DLVO theory showed attractive forces between the oil particles
      and micro-bubbles are significantly more prevalent in short CCLs solutions of
      imidazolium-based ILs in low concentrations, namely [C0mim][Cl] and [C2mim][Cl]
      at a maximum zeta potential difference of 75.3mV. The results from CA
      measurements follows similarly whereby low concentrations of ILs with short CCLs
      were in favor for the bubble-particle attachment process with angles ranging
      between 93.95 degrees  for [C0mim][Cl] and 97.28 degrees  for [C2mim][Cl]. IFT
      which is important in reducing coalescence for the preferential BPA process to
      occur in flotation decreases with an increase of CCL and concentration of IL.

PMID- 28755641
TI  - A visual guide to gene/optothermal synergy therapy nanosystem using tungsten
      oxide.
AB  - Combination of gene therapy and photothermal therapy (PTT) has drawn much
      attention in cancer therapy in recent years. However, this joint treatment
      process lacks fluorescence imaging visualization guidance that limits its
      clinical applications in oncotherapy. Herein, we report the use of gene therapy
      and tungsten oxide (W18O49, WO) synthetized with template method for combined PTT
      of cancer. In this system, a novel nanoplatform, with Bax gene, WO and
      indocyanine green (ICG) loaded in mesoporous silica nanoparticle had been
      successfully constructed, which was used as the near-infrared imaging-guided
      gene/optothermal multi-modal oncotherapy. These nanoparticles could achieve a
      synergistic therapy effect of gene therapy and PTT for tumor under 808nm near
      infrared (NIR) laser excitation. In vivo animal experiments showed that they
      could cause solid tumor regression under 808nm NIR light irradiation, revealing
      the potential of these nanocomposites as a fluorescence imaging-guided multi
      modal therapeutic nanosystem for tumor visual synergistic treatment.

PMID- 28755642
TI  - Green synthesis of copper nanoparticles using Plantago asiatica leaf extract and
      their application for the cyanation of aldehydes using K4Fe(CN)6.
AB  - Copper nanoparticles (Cu NPs) were synthesized via a green method by using of
      Plantago asiatica leaf extract as natural solvent and reaction biomedia under
      environmentally benign reaction conditions. It was observed that use of Plantago
      asiatica leaf extract makes a simple, eco-friendly and cost effective method for
      the preparation of the Cu NPs and can reduce copper ions into Cu(0) within 5min
      of reaction time without using any stabilizer or surfactant agent. The progress
      of the reaction was monitored using UV-Visible spectroscopy. Polyphenolics could
      be adsorbed on the surface of Cu NPs, possibly by interaction through pi
      electrons interaction in the absence of other strong ligating agents. The
      catalytic activity of the Cu NPs was evaluated by cyanation of aldehydes in the
      extract as a green solvent. This method provided several advantages such as
      cleaner easy work-up, shorter reaction time and higher yield. Cu NPs were
      characterized by FT-IR, UV-Vis, TEM, X-ray diffraction and the synthesized
      products were characterized by FT-IR and 1H NMR.

PMID- 28755643
TI  - Toward understanding the anticorrosive mechanism of some thiourea derivatives for
      carbon steel corrosion: A combined DFT and molecular dynamics investigation.
AB  - The mutually corroborated density functional theory (DFT) and molecular dynamics
      (MD) simulation methodology were employed to evaluate the inhibition performance
      of three thiourea derivatives (Inh1, Inh2, and Inh3) on carbon steel corrosion.
      Experimental results have shown that the corrosion rate follows the order:
      Inh3>Inh2>Inh1. Quantum chemical descriptors such as the frontier orbital
      energies (EHOMO and ELUMO), the energy gap between ELUMO and EHOMO (DeltaE),
      dipole moment (MU), and Fukui index have been calculated and discussed. Some
      significant factors such as solvent, temperature, and coverage have been
      considered when investigating the adsorption of aforementioned thiourea
      derivatives on Fe(110) surface. Our results provide important atomic/molecular
      insights into the anticorrosive mechanism of inhibitor molecules, which could
      help in understanding the organic-metal interface and designing more appropriate
      organic corrosion inhibitors.

PMID- 28755644
TI  - Impact of potent bioremediation enhancing plant extracts on Raoultella
      ornithinolytica properties.
AB  - Long-term contact of microorganisms with different compounds in the environment
      can cause significant changes in cell metabolism. Surfactants adsorption on cell
      surface or incorporation in the cell membrane, lead to their modification, which
      helps microorganisms adopt to the conditions of metabolic stress. The main
      objective of this study was to investigate the effects of three saponin-reach
      plant extracts from Hedera helix, Saponaria officinalis and Sapindus mucorossi on
      growth and adaptation of Raoultella ornithinolytica to high concentrations of
      these substances. For this purpose we investigated cell surface properties,
      membrane fatty acids and genetic changes of the microorganisms. The results
      revealed that prolonged exposure of the microorganisms to high concentrations of
      these surfactants can induce genetic changes of their genes. Moreover, the
      adaptation to contact with high concentrations of saponins was also associated
      with changes in composition of fatty acids responsible for the stabilisation of
      membrane structure and the increase in membrane permeability. The changes
      affected also the outer layer of cells. A significant increase (p < 0.05) in the
      cell surface hydrophobicity of tested strain was also observed. The cells after
      long-term contact with S. officinalis and S. mucorossi acquire properties that
      may be favourable in hydrophobic substances bioremediation.

PMID- 28755645
TI  - Determination and prediction of octanol-air partition coefficients for
      organophosphate flame retardants.
AB  - Organophosphate flame retardants (OPFRs) have attracted wide concerns due to
      their toxicities and ubiquitous occurrence in the environment. In this work,
      Octanol-air partition coefficient (KOA) for 14 OPFRs including 4 halogenated
      alkyl-, 5 aryl- and 5 alkyl-OPFRs, were estimated as a function of temperature
      using a gas chromatographic retention time (GC-RT) method. Their log KOA-GC
      values and internal energies of phase transfer (DeltaOAU/kJmol-1) ranged from
      8.03 to 13.0 and from 69.7 to 149, respectively. Substitution pattern and molar
      volume (VM) were found to be capable of influencing log KOA-GC values of OPFRs.
      The halogenated alkyl-OPFRs had higher log KOA-GC values than aryl- or alkyl
      OPFRs. The bigger the molar volume was, the greater the log KOA-GC values
      increased. In addition, a predicted model of log KOA-GC versus different relative
      retention times (RRTs) was developed with a high cross-validated value (Q2(cum))
      of 0.951, indicating a good predictive ability and stability. Therefore, the log
      KOA-GC values of the remaining OPFRs can be predicted by using their RRTs on
      different GC columns.

PMID- 28755646
TI  - Preparation of green alga-based activated carbon with lower impregnation ratio
      and less activation time by potassium tartrate for adsorption of chloramphenicol.
AB  - Potassium tartrate (C4H6K2O7) was utilized as a novel activating agent to prepare
      activated carbon with relatively high specific surface area by using less
      activating agent and activation time from marine waste-green alga (Enteromorpha
      prolifera) for the first time. The influences of activation temperature,
      impregnation ratio and activation time on the pore structure were investigated to
      obtain the optimum conditions (activation temperature: 700 degrees C,
      impregnation ratio: 1:1, and activation time: 30min). Meanwhile, the activation
      temperature was evaluated to be the essential factor that dominated the form of
      pore structure in activated carbon. The green alga-based activated carbon that
      was prepared under optimum conditions has shown the high surface area of 1692m2/g
      and total pore volume of 1.22cm3/g, which could be used as an effective adsorbent
      to remove chloramphenicol. The thermodynamic data of chloramphenicol were well
      fitted by Langmuir isotherm model and the green alga-based activated carbon has
      showed high adsorption capacity of 709.2mg/g towards chloramphenicol.

PMID- 28755647
TI  - Health risk assessment of heavy metals in fish and accumulation patterns in food
      web in the upper Yangtze River, China.
AB  - : This study aims to concern the distribution of As, Cr, Cd, Hg, Cu, Zn, Pb and
      Fe in surface sediment, zoobenthos and fishes, and quantify the accumulative
      ecological risk and human health risk of metals in river ecological system based
      on the field investigation in the upper Yangtze River. The results revealed high
      ecological risk of As, Cd, Cu, Hg, Zn and Pb in sediment. As and Cd in fish
      presented potential human health risk of metals by assessing integrated target
      hazard quotient results based on average and maximum concentrations,
      respectively. No detrimental health effects of heavy metals on humans were found
      by daily fish consumption. While, the total target hazard quotient (1.659)
      exceeding 1, it meant that the exposed population might experience
      noncarcinogenic health risks from the accumulative effect of metals. Ecological
      network analysis model was established to identify the transfer routes and
      quantify accumulative effects of metals on river ecosystem. Control analysis
      between compartments showed large predator fish firstly depended on the
      omnivorous fish. Accumulative ecological risk of metals indicated that zoobenthos
      had the largest metal propagation risk and compartments located at higher trophic
      levels were not easier affected by the external environment pollution. CAPSULE: A
      potential accumulative ecological risk of heavy metal in the food web was
      quantified, and the noncarcinogenic health risk of fish consumption was revealed
      for the upper reach of the Yangtze River.

PMID- 28755648
TI  - Cerebral PET glucose hypometabolism in subjects with mild cognitive impairment
      and higher EEG high-alpha/low-alpha frequency power ratio.
AB  - In Alzheimer's disease (AD) research, both 2-deoxy-2-(18F)fluoro-D-glucose (FDG)
      positron emission tomography (PET) and electroencephalography (EEG) are reliable
      investigational modalities. The aim of this study was to investigate the
      associations between EEG High-alpha/Low-alpha (H-alpha/L-alpha) power ratio and
      cortical glucose metabolism. A total of 23 subjects with mild cognitive
      impairment (MCI) underwent FDG-PET and EEG examinations. H-alpha/L-alpha power
      ratio was computed for each subject and 2 groups were obtained based on the
      increase of the power ratio. The subjects with higher H-alpha/L-alpha power ratio
      showed a decrease in glucose metabolism in the hub brain areas previously
      identified as typically affected by AD pathology. In subjects with higher H
      alpha/L-alpha ratio and lower metabolism, a "double alpha peak" was identified in
      the EEG spectrum and a U-shaped correlation between glucose metabolism and
      increase of H-alpha/L-alpha power ratio has been found. Moreover, in this group,
      a conversion rate of 62.5% at 24 months was detected, significantly different
      from the chance percentage expected. The neurophysiological meaning of the
      interplay between alpha oscillations and glucose metabolism and the possible
      interest of the H-alpha/L-alpha power ratio as a clinical biomarker in AD have
      been discussed.

PMID- 28755649
TI  - Tests of linear and nonlinear relations between cumulative contextual risk at
      birth and psychosocial problems during adolescence.
AB  - This study tested whether there are linear or nonlinear relations between
      prenatal/birth cumulative risk and psychosocial outcomes during adolescence.
      Participants (n = 6963) were taken from the Northern Finland Birth Cohort Study
      1986. The majority of participants did not experience any contextual risk factors
      around the time of the target child's birth (58.1%). Even in this low-risk
      sample, cumulative contextual risk assessed around the time of birth was related
      to seven different psychosocial outcomes 16 years later. There was some evidence
      for nonlinear effects, but only for substance-related outcomes; however, the form
      of the association depended on how the cumulative risk index was calculated.
      Gender did not moderate the relation between cumulative risk and any of the
      adolescent psychosocial outcomes. Results highlight the potential value of using
      the cumulative risk framework for identifying children at birth who are at risk
      for a range of poor psychosocial outcomes during adolescence.

PMID- 28755650
TI  - Best friends' interactions and substance use: The role of friend pressure and
      unsupervised co-deviancy.
AB  - Best friends exert a substantial influence on rising alcohol and marijuana use
      during adolescence. Two mechanisms occurring within friendship - friend pressure
      and unsupervised co-deviancy - may partially capture the way friends influence
      one another. The current study aims to: (1) examine the psychometric properties
      of a new instrument designed to assess pressure from a youth's best friend and
      unsupervised co-deviancy; (2) investigate the relative contribution of these
      processes to alcohol and marijuana use; and (3) determine whether gender
      moderates these associations. Data were collected through self-report
      questionnaires completed by 294 Canadian youths (62% female) across two time
      points (ages 15-16). Principal component analysis yielded a two-factor solution
      corresponding to friend pressure and unsupervised co-deviancy. Logistic
      regressions subsequently showed that unsupervised co-deviancy was predictive of
      an increase in marijuana use one year later. Neither process predicted an
      increase in alcohol use. Results did not differ as a function of gender.

PMID- 28755651
TI  - Pyramiding resistance-conferring gene sequences in crops.
AB  - Plant viruses can cause devastating diseases in many crops around the world.
      Genetic resistance and the adoption of resistant crop cultivars is the most
      desirable strategy to manage viruses. Single or multiple sources of resistance
      derived from host and/or virus gene sequences are used to develop resistant crop
      plants. Pyramiding sources of resistance is essential for achieving broad
      spectrum and durable resistance and for protecting crops from commonly occurring
      mixed virus infections. Stacking resistance-conferring gene sequences into single
      crop cultivars is achieved by first, conventional breeding and the use of
      dominant and recessive host genes; second, genetic engineering and the deployment
      of virus-derived gene sequences or modified small plant RNAs for antiviral RNA
      interference defense, or of programmable nucleases to target viral gene sequences
      or to alter host factors that are critical to complete the virus infection cycle;
      and third, a combination of conventional breeding and genetic engineering. These
      strategies are successfully used to mitigate the effect of viruses. It is
      anticipated that the development of virus resistant crops carrying multiple
      resistance-conferring gene sequences will be further facilitated by progress at
      unraveling underpinnings of virus-host interactions, and at determining the
      sequence of more crop genomes.

PMID- 28755652
TI  - Transfer and modification of NLR proteins for virus resistance in plants.
AB  - NLR proteins confer resistance to multiple types of biotrophic pathogens,
      including viruses. NLRs are highly variable in sequence, suggesting that they are
      under selection pressure, but also that they may be manipulated to generate
      proteins with new recognition specificities. However, transferring of effective
      NLRs and engineering new specificities is subject to a number of constraints.
      Recent insights into NLR function suggest a number of reasons for these
      difficulties and new techniques have increased our ability to identify effective
      NLRs. This review discusses how this new information may allow researchers to
      better take advantage of the potential of NLRs for creating virus-resistant
      plants, including the identification, modification and transfer of NLRs as well
      as re-engineering NLRs to recognize viruses based on viral protein function.

PMID- 28755653
TI  - Situating mental health work in place: Qualitative findings from interviews with
      Veterans in Southeastern Louisiana and Northern California.
AB  - Most chronic illness management occurs outside clinics and hospitals, in the
      everyday lives of individuals. We use data from semi-structured interviews with
      37 veterans from Southeastern Louisiana and Northern California to illustrate how
      "health work" for mental health concerns are shaped by place. Using health work
      as an orienting concept for analysis, we discerned variation between the two
      study sites in how Veterans used interacting with the natural environment,
      cultivating time alone, and religious practice to manage their mental health and
      well-being. Through these findings, we advocate for a situated notion of health
      work that is mindful of how health-related behaviors are shaped by place and the
      attributes that constitute place.

PMID- 28755654
TI  - Effects of Bone Marrow Mesenchymal Stem Cells-Conditioned Medium on Tibial
      Partial Osteotomy Model of Fracture Healing in Hypothyroidism Rats
AB  - Background: Hypothyroidism is associated with dysfunction of the bone turnover
      with reduced osteoblastic bone formation and osteoclastic bone resorption.
      Mesenchyme stem cells (MSCs) secrete various factors and cytokines that may
      stimulate bone regeneration.  The aim of this study was to determine the effects
      of MSCs-conditioned medium (CM) in hypothyroidism male rats after inducing bone
      defect. Methods: : In this study, 24 male rats were randomly assigned to three
      groups: (I) hypothyroidism+bone defect (HYPO), (II) hypothyroidism+bone defect+CM
      (HYPO+CM), and (III) no hypothyroidism+bone defect (control). Four weeks after
      surgery, the right tibia was removed, and immediately, biomechanical and
      histological examinations were performed. Results: The results showed a
      significant reduction in bending stiffness (32.64+/-3.99), maximum force (14.63+/
      1.89), high stress load (7.59+/-2.31), and energy absorption (12.68+/-2.12) at
      the osteotomy site in hypothyroidism rats in comparison to the control and
      hypothyroidism+condition medium groups (P<0.05). There was also a significant
      decrease in the trabecular bone volume (3.86+/-3.88) and the number of osteocytes
      (5800+/-859.8) at the osteotomy site in hypothyroidism rats compared to the
      control and hypothyroidism+condition medium groups (P<0.01 and P<0.02,
      respectively). Conclusion: The present study suggests that the use of the CM can
      improve the fracture regeneration and accelerates bone healing at the osteotomy
      site in hypothyroidism rats.

PMID- 28755655
TI  - Therapeutic effects of Iranian herbal extracts against Trichomonas vaginalis
AB  - Trichomonas vaginalis is a flagellated parasite affecting about 276 million
      people annually worldwide. Tricomoniasis is associated with different
      complications in pregnant women and infants. 5'-nitroimidazole derivatives
      (metronidazole, ornidazole, and tinidazole) are FDA approved drugs recommended
      for trichomoniasis treatment. Treatment with metronidazole 5'-nitroimidazole
      derivatives is associated with many side effects, and drug resistance to
      metronidazole has been reported in some cases. Recently, many attempts have been
      made to evaluate the effects of plants on causative agents of vaginal infections.
      In our research, the national and international databases were searched and the
      effects of various herbal extracts on T. vaginalis in Iran were reviewed from
      2006 to 2016. In articles investigated, some plants had favorable antitrichomonal
      effects and needed to be further investigated. All the plant extracts have only
      been evaluated in vitro. Surveys of different articles in this review show that
      the active ingredients present in different parts of plants, including aerial
      parts, leaves, flowers, stems, and root can be suitable sources for introducing
      and developing new antitrichomonal compounds.

PMID- 28755656
TI  - Health status of adolescents in the Tibetan plateau area of western China: 6
      years after the Yushu earthquake.
AB  - BACKGROUND: An earthquake struck Yushu in Qinghai province of China on April 14,
      2010, causing 2698 deaths and 12,135 injuries.The present study aimed to assess
      the health status, and associated determinants, of child survivors in the
      epicenter of the Yushu earthquake 6 years after the event. METHODS: A cross
      sectional survey was performed among students from two junior schools in Yushu
      County. Descriptive statistics, t-tests, ANOVA, Wilcoxon rank sum tests, Kruskal
      Wallis H tests and stepwise linear regression analysis were used for data
      analysis. RESULTS: The mean scores onmental component summary (MCS)and physical
      component summary (PCS) were 42.13 (SD 7.32) and 42.04 (SD 8.07), respectively.
      Lower PCS in the aftermath of an earthquake was associated with being trapped/in
      danger, injured to self, receiving no escape training while lowerMCS in the
      aftermath of an earthquake was associated with a lower grade level, not living
      with parents, fear during the earthquake, death in the family, and not receiving
      psychological counseling after the earthquake. CONCLUSIONS: In conclusion, the
      results of the present study help to expand our knowledge regarding the health
      status of child survivors 6 years after the Yushu earthquake. Our study provides
      evidence-based suggestions for specific long-term health interventions in such
      vulnerable populations.

PMID- 28755657
TI  - No-touch methods of terminal cleaning in the intensive care unit: results from
      the first large randomized trial with patient-centred outcomes.

PMID- 28755658
TI  - Enterogenous cyst of pediatric testis: a case report.
AB  - BACKGROUND: An enterogenous cyst is a rare entity categorized as an intestinal
      cyst. In most cases, enterogenous cysts are seen in the mediastinum, peritoneal
      cavity, spinal canal, subarachnoid space, and cerebral ventricle. CASE
      PRESENTATION: A 14-year-old Asian (Japanese) boy reported feeling pain in his
      left groin, and a mass was found. We did not perform orchiectomy because
      intraoperative frozen sections showed no malignant findings. On histological
      examination the resected specimens contained columnar epithelium surrounded by
      smooth muscle. Based on these findings, an enterogenous cyst was diagnosed. Few
      cases of enterogenous cysts of the testis have been described. CONCLUSION: We
      encountered a case of an enterogenous cyst of a pediatric testis.

PMID- 28755659
TI  - Authentication of collagen VI antibodies.
AB  - BACKGROUND: Collagen VI is a ubiquitously-expressed macromolecule that forms
      unique microfibrillar assemblies in the extracellular matrix. Mutations in the
      COL6A1, COL6A2 and COL6A3 genes result in congenital muscular dystrophy, arguing
      that collagen is critical for skeletal muscle development and function.
      Antibodies against collagen VI are important clinical and diagnostic tools in
      muscular dystrophy. They are used to confirm genetic findings by detecting
      abnormalities in the distribution, organization and overall levels of collagen VI
      in cells and tissues isolated from patients. METHODS: Many antibodies have been
      raised against tissue-purified collagen VI and individual collagen VI chains,
      however few have been properly validated for sensitivity and chain specificity.
      To address this deficiency, we compared the ability of 23 commercially-available
      antibodies to detect extracellular collagen VI by immunohistochemistry on frozen
      tissue sections. To determine chain specificity, immunoblot analyses were
      conducted on cell lysates isolated from cells transfected with cDNAs for each
      individual chain and cells expressing all three chains together. RESULTS: Our
      analyses identified 15 antibodies that recognized tissue collagen VI by
      immunohistochemistry at varying intensities and 20 that successfully detected
      collagen VI by immunoblotting. Three antibodies failed to recognize collagen VI
      by either method under the conditions tested. All chain-specific antibodies that
      worked by immunoblotting specifically recognized their correct chain, and no
      other chains. CONCLUSIONS: This series of side-by-side comparisons reveal at
      least two antibodies specific for each chain that work well for
      immunohistochemistry on frozen sections. This validation study expands the
      repertoire of antibodies available for muscular dystrophy studies caused by
      defects in collagen VI.

PMID- 28755660
TI  - Computational and experimental assessment of influences of hemodynamic shear
      stress on carotid plaque.
AB  - BACKGROUND: Studies have identified hemodynamic shear stress as an important
      determinant of endothelial function and atherosclerosis. In this study, we assess
      the influences of hemodynamic shear stress on carotid plaques. METHODS: Carotid
      stenosis phantoms with three severity (30, 50, 70%) were made from 10% polyvinyl
      alcohol (PVA) cryogel. The phantoms were placed in a pulsatile flow loop with the
      same systolic/diastolic phase (35/65) and inlet flow rate (16 L/h). Ultrasonic
      particle imaging velocimetry (Echo PIV) and computational fluid dynamics (CFD)
      were used to calculate the velocity profile and shear stress distribution in the
      carotid stenosis phantoms. Inlet/outlet boundary conditions used in CFD were
      extracted from Echo PIV experiments to make sure that the results were
      comparable. RESULTS: Echo PIV and CFD results showed that velocity was largest in
      70% than those in 30 and 50% at peak systole. Echo PIV results indicated that
      shear stress was larger in the upper wall and the surface of plaque than in the
      center of vessel. CFD results demonstrated that wall shear stress in the upstream
      was larger than in downstream of plaque. There was no significant difference in
      average velocity obtained by CFD and Echo PIV in 30% (p = 0.25). Velocities
      measured by CFD in 50% (93.01 cm/s) and in 70% (115.07 cm/s) were larger than
      those by Echo PIV in 50% (60.26 +/- 5.36 cm/s) and in 70% (89.11 +/- 7.21 cm/s).
      CONCLUSIONS: The results suggested that Echo PIV and CFD could obtain hemodynamic
      shear stress on carotid plaques. Higher WSS occurred in narrower arteries, and
      the shoulder of plaque bore higher WSS than in bottom part.

PMID- 28755661
TI  - Association of alpha A-crystallin polymorphisms with susceptibility to nuclear
      age-related cataract in a Han Chinese population.
AB  - BACKGROUND: Alpha A-crystallin (CRYAA) is considered critical for the maintenance
      of lens transparency and is related to the pathogenesis of age-related cataracts
      (ARCs), especially the nuclear subtype. As the 5' untranslated region (5' UTR)
      modulates gene expression, the purpose of current study was to investigate
      whether single nucleotide polymorphisms (SNPs) in the 5' UTR of CRYAA were
      associated with susceptibility to ARC in a Han Chinese population and to clarify
      the mechanism of this association. METHODS: SNPs in the 5' UTR (-1 to -1000) of
      CRYAA were identified in 243 nuclear ARC patients and 263 controls using
      polymerase chain reaction and DNA sequencing. Allele and genotype frequencies
      were calculated and compared between two groups. Haploview 4.2 was used to
      calculate the linkage disequilibrium index, and the SHEsis analysis platform was
      used to infer haplotype construction. A dual-luciferase reporter gene assay was
      used for transcription of CRYAA in the presence of a protective haplotype with
      individual SNP alteration, Chromatin immunoprecipitation (ChIP) was employed to
      determine whether SNPs regulated CRYAA expression by altering the binding
      affinity of transcription factors. RESULTS: Three polymorphisms were identified
      in the 5' UTR of CRYAA: rs3761381 (P = 0.000357, odds ratio [OR] = 1.837),
      rs13053109 (P = 0.788, OR = 1.086), and rs7278468 (P = 0.00136, OR = 0.652). The
      haplotype C-G-T (P = 0.0014, OR = 1.536) increased the risk of nuclear ARC,
      whereas the haplotype T-G-G (P = 0.00029, OR = 0.535) decreased the risk. The
      haplotype C-G-T decreased CRYAA transcription through rs7278468, which is located
      in the binding site of specificity protein 1 (Sp1). Furthermore, the G allele of
      rs7278468 increased CRYAA transcription by enhancing the binding affinity of Sp1.
      CONCLUSIONS: These data indicate that the CRYAA polymorphism is a genetic marker
      of inter-individual differences in the risk of nuclear ARC.

PMID- 28755663
TI  - Transitioning From Perioperative Staff Nurse to Perioperative Educator.
AB  - Perioperative nurses who enjoy teaching may wish to become staff development
      educators. The shift to this new role requires a transition period during which
      the new educator acquires the knowledge, skills, and attitudes integral to
      mastering the job. A systematic approach to achieving baseline competencies in
      the educator role helps to ensure a successful conversion from providing direct
      patient care to supporting the educational needs of staff members.

PMID- 28755662
TI  - Substrate stiffness governs the initiation of B cell activation by the concerted
      signaling of PKCbeta and focal adhesion kinase.
AB  - The mechanosensing ability of lymphocytes regulates their activation in response
      to antigen stimulation, but the underlying mechanism remains unexplored. Here, we
      report that B cell mechanosensing-governed activation requires BCR signaling
      molecules. PMA-induced activation of PKCbeta can bypass the Btk and PLC-gamma2
      signaling molecules that are usually required for B cells to discriminate
      substrate stiffness. Instead, PKCbeta-dependent activation of FAK is required,
      leading to FAK-mediated potentiation of B cell spreading and adhesion responses.
      FAK inactivation or deficiency impaired B cell discrimination of substrate
      stiffness. Conversely, adhesion molecules greatly enhanced this capability of B
      cells. Lastly, B cells derived from rheumatoid arthritis (RA) patients exhibited
      an altered BCR response to substrate stiffness in comparison with healthy
      controls. These results provide a molecular explanation of how initiation of B
      cell activation discriminates substrate stiffness through a PKCbeta-mediated FAK
      activation dependent manner.

PMID- 28755664
TI  - Introducing Perioperative Nursing as a Foundation for Clinical Practice.
AB  - This article describes one school's experience in providing a perioperative
      nursing course as a first clinical course in a bachelor of science in nursing
      curriculum. This innovation reframes the perspective on perioperative nursing
      from that of an elective clinical specialty that is not essential to basic
      nursing education to a practice setting that provides key foundational clinical
      learning experiences for the novice nursing student. A strong academic-practice
      partnership; effective preparation for key stakeholders including nursing staff
      members, preceptors, and students; and collaboration with AORN were essential
      elements in the success of this clinical learning innovation. We describe
      learning outcomes, lessons learned, and future plans for enhancing and expanding
      this course.

PMID- 28755665
TI  - The Effectiveness of Nurse Residency Programs on Retention: A Systematic Review.
AB  - New graduates account for the highest numbers of nurses entering and exiting the
      profession. Turnover is costly, especially in specialty settings. Nurse residency
      programs are used to retain new graduates and assist with their transition to
      nursing practice. The purpose of this systematic review of the literature was to
      examine new graduate nurse residency programs, residents' perceived satisfaction,
      and retention rates, and to make recommendations for implementation in
      perioperative settings. Results indicate increased retention rates for new
      graduates participating in residency programs and that residency participants
      experienced greater satisfaction with their orientation than those not
      participating in residency programs. Residency participants also perceived the
      residency as beneficial. Because residency programs vary in curricula and length,
      effectively comparing outcomes is difficult. More longitudinal data are needed.
      Data on residency programs specific to perioperative nursing are lacking.
      Considering the aging perioperative nursing workforce, residency programs could
      address critical needs for succession planning.

PMID- 28755667
TI  - Guideline Summary: Minimally Invasive Surgery, Part 2-Hybrid ORs.

PMID- 28755666
TI  - Guideline Implementation: Minimally Invasive Surgery, Part 2-Hybrid ORs.
AB  - Performing both surgical and imaging procedures in a hybrid OR can increase
      efficiency by reducing the number of patient transfers between departments and
      the number of patient hand overs between personnel. A hybrid OR is, however, a
      complex environment that requires integrating the knowledge and skills of
      personnel from multiple disciplines to create a successful workflow. When
      magnetic resonance imaging (MRI) equipment is installed in the hybrid OR,
      additional precautions are required to help ensure the environment is safe for
      patients and personnel. AORN's updated "Guideline for minimally invasive surgery"
      provides guidance for personnel designing and working in hybrid ORs and MRI
      hybrid ORs. This article focuses on key points of the guideline that address
      hybrid OR configuration, hybrid OR staffing, and mitigating risks associated with
      intraoperative MRI. Perioperative RNs should review the complete guideline for
      additional information and for guidance when writing and updating policies and
      procedures.

PMID- 28755668
TI  - Simulation-Based Training: Malignant Hyperthermia.

PMID- 28755669
TI  - Clinical Issues-August 2017.
AB  - Caring for patients with tattoos undergoing magnetic resonance imaging (MRI)
      procedures Key words: magnetic resonance imaging, tattoos. Reducing slips, trips,
      and falls caused by electrical cords on the procedure room floor Key words:
      slips, trips, falls, electrical cords, equipment booms. Classifying surgical limb
      amputation wounds Key words: wound classification, documentation, amputation.
      Preventing postoperative pressure alopecia Key words: alopecia, occipital
      neuropathy, scalp massage. Using prophylactic dressings to prevent pressure
      injury Key words: prophylactic dressings, silicone foam dressings, sacral
      dressings, heel dressings, pressure injury.

PMID- 28755670
TI  - Evidence appraisal of Paim CPP, Goldmeier S. Development of an educational game
      to set up surgical instruments on the Mayo stand or back table: applied research
      in production technology.: JMIR Serious Games. 2017;5(1):e1.
      doi:10.2196/games.6048.

PMID- 28755671
TI  - Guideline at a Glance: Hand Hygiene.

PMID- 28755672
TI  - Robotic Surgery: Risks vs. Rewards.

PMID- 28755673
TI  - Embrace Action: Join and Participate in AORN.

PMID- 28755674
TI  - Nursing as Knowledge Work: The Imperative for Lifelong Learning.

PMID- 28755675
TI  - Professional Development Strategies to Enhance Nurses' Knowledge and Maintain
      Safe Practice.
AB  - Maintaining competence is a professional responsibility for nurses. Individual
      nurses are accountable for their practice, as outlined in the American Nurses
      Association's Nursing: Scope and Standards of Practice. Nurses across clinical
      settings face the sometimes daunting challenge of staying abreast of regulatory
      mandates, practice changes, equipment updates, and other workplace expectations.
      In the complex, evolving perioperative setting, professional development is a
      priority, and the need for ongoing education is critical. However, nurses'
      efforts to engage in their own development can be hampered by a lack of time,
      limited access to educational resources, or cost concerns. This article provides
      an overview of nursing professional development and offers some resources to help
      individual nurses maintain or enhance their knowledge, skills, and attitudes.

PMID- 28755676
TI  - [Drugs: When appearances mislead].

PMID- 28755677
TI  - Proceedings of the 27th meeting of the German Society for Parasitology 2016.

PMID- 28755678
TI  - Cognitive impairment in Chinese IIDDs revealed by MoCA and P300.
AB  - To investigate the value of MoCA and auditory P300 as a cognitive assessment tool
      in chinese idiopathic inflammatory-demyelinating diseases (IIDDs), eighty three
      consecutive patients with IIDDs and thirteen sex- and age-matched healthy
      controls were recruited in the study. MMSE, MoCA and auditory P300 potential were
      administrated to each participant. The percentage of cognitive impairment in
      IIDDs patients was 24.1% by using MMSE, while the percentage was 81.9% by using
      MoCA. The majority of IIDDs participants had MMSE scores in the normal range. In
      contrast, few IIDDs participants scored in the normal range on the MoCA. Age,
      EDSS and depression correlated negatively with the total score of MoCA and MMSE.
      Years of education correlated positively with MoCA and MMSE. ADEM patients scored
      lower on all MoCA subtests. Prolonged latency P300 which negatively correlated
      with MoCA and reduced P300 amplitude which positively correlated with MoCA were
      detected in IIDDs patients. Thus MoCA is superior to the MMSE as a cognitive
      impairment scan tool and P300 is useful for detecting cogntive deficiency in
      chinese IIDDs.

PMID- 28755679
TI  - Effect of walking on sand on gait kinematics in individuals with multiple
      sclerosis.
AB  - BACKGROUND: Walking in the real-world involves negotiating challenging or uneven
      surfaces, including sand. This can be challenging for people with Multiple
      Sclerosis (PWMS) due to motor deficits affecting the lower extremities. The study
      objective was to characterise kinematic gait adaptations made by PWMS when
      walking on sand and describe any immediate post-adaptation effects. METHODS: 17
      PWMS (mean age 51.4 +/- 5.5, Disease Steps 2.4 +/- 1.0), and 14 age-and gender
      matched healthy adults (HA) took part in a case-control study. 3D gait analysis
      was conducted using an eight-camera Vicon motion capture system. Each participant
      completed walking trials over level ground (baseline), sand (gait adaptation
      response), and again level ground (post-adaptation). Spatiotemporal data and
      kinematic data for the hip knee and ankle were recorded. RESULTS: At baseline
      PWMS showed significantly less total lower limb flexion (p<0.05) compared to HA.
      PWMS adapted to walking on sand by significantly increasing hip and knee flexion
      and ankle dorsiflexion (p<0.05) during swing, resulting in an overall 23 degrees 
      greater total lower limb flexion (p<0.05), reaching values within normal range.
      During the return to level ground walking values of temporal-spatial and
      kinematic parameters returned towards baseline values. CONCLUSIONS: PWMS adapted
      to walking on sand by increasing lower limb flexion during swing, and returned to
      their gait pattern to near baseline levels, in a manner similar to but with
      values not equalling HA. Further work is required to determine whether this mode
      of walking has potential to act as a gait retraining strategy to increase flexion
      of the lower limb.

PMID- 28755680
TI  - Capillary leak syndrome in neuromyelitis optica treated with rituximab.
AB  - 61-year-old woman with Neuromyelitis optica (NMO) diagnosis treated with
      rituximab was referred to our hospital with severe hypovolemic shock and
      anasarca. The laboratory findings showed marked hemoconcentration and a decrease
      in total serum protein. She developed a multiple organ failure and died three
      hours later. We diagnosed the patient as having capillary leak syndrome (CLS).
      CLS is a very rare condition caused by unexplained episodic capillary
      hyperpermeability, which can be idiopathic or secondary to some conditions like
      infection, malignant disease and some drugs like monoclonal antibodies. We
      reported the first CLS case in NMO patient treated with rituximab.

PMID- 28755681
TI  - EBV and MS: Major cause, minor contribution or red-herring?
AB  - Multiple Sclerosis (MS) is a chronic neurological disease with genetic and
      environmental risk factors. Epstein Barr-Virus (EBV) has been closely associated
      with MS but with a significant amount of conflicting evidence. Some of the
      evidence for EBV involvement in MS includes: almost 100% of MS patients showing
      past EBV infection, an association with Infectious Mononucleosis (acute EBV
      infection), higher titres of EBV antibodies associated with an increased risk of
      MS development, and an overall altered immune response to EBV found in peripheral
      blood and the CNS of MS patients. However, evidence for EBV presence in the CSF
      and T cell responses to EBV in MS have been particularly conflicting. Several
      hypotheses have been proposed for direct and indirect EBV involvement in MS such
      as 1) Molecular Mimicry 2) Mistaken Self 3) Bystander Damage and 4) Autoreactive
      B cells infected with EBV. More recently, an association between EBV and human
      endogenous retrovirus in MS has been shown, which may provide an alternative
      pathogenetic target for MS treatment. However, if EBV is not the major
      contributor to MS and is instead one of several viral or infectious agents able
      to elicit a similar altered immune response, MS development may be the result of
      a failure of viral clearance in general. This review aims to evaluate the
      evidence for the currently discussed theories of EBV involvement in MS
      pathogenesis.

PMID- 28755682
TI  - The effect of exercise training in adults with multiple sclerosis with severe
      mobility disability: A systematic review and future research directions.
AB  - INTRODUCTION: There is evidence for the benefits of exercise training in persons
      with multiple sclerosis (MS). However, these benefits have primarily been
      established in individuals with mild-to-moderate disability (i.e., Expanded
      Disability Status Scale [EDSS] scores 1.0-5.5), rather than among those with
      significant mobility impairment. Further, the approaches to exercise training
      that have been effective in persons with mild-to-moderate MS disability may not
      be physically accessible for individuals with mobility limitations. Therefore,
      there is a demand for an evidence-base on the benefits of physically accessible
      exercise training approaches for managing disability in people with MS with
      mobility impairment. OBJECTIVE: To conduct a systematic review of the current
      literature pertaining to exercise training in individuals with multiple sclerosis
      (MS) with severe mobility disability. METHODS: Four electronic databases (PubMed,
      EMBASE, OvidMEDLINE, and PsychINFO) were searched for relevant articles published
      up until October 2016. The review focused on English-language studies that
      examined the effect of exercise training in people with MS with severe mobility
      disability, characterized as the need for assistance in ambulation or EDSS score
      >= 6.0. The inclusion criteria involved full-text articles that: (i) included
      participants with a diagnosis of MS; (ii) included primarily participants with a
      reported EDSS score >= 6.0 and/or definitively described disability consistent
      with this level of neurological impairment; and (iii) implemented a prospective,
      structured exercise intervention. Data were analyzed using a descriptive approach
      and summarized by exercise training modality (conventional or adapted exercise
      training), and by outcome (disability, physical fitness, physical function, and
      symptoms and participation). RESULTS: Initially, 1164 articles were identified
      and after removal of duplicates, 530 articles remained. In total, 512 articles
      did not meet the inclusion criteria. 19 articles were included in the final
      review. Five studies examined conventional exercise training (aerobic and
      resistance training), and thirteen studies examined adapted exercise modalities
      including body-weight support treadmill training (BWSTT), total-body recumbent
      stepper training (TBRST), and electrical stimulation cycling (ESAC). Outcomes
      related to mobility, fatigue, and quality of life (QOL) were most frequently
      reported. Two of five studies examining conventional resistance exercise training
      reported significant improvements in physical fitness, physical function, and/or
      symptomatic and participatory outcomes. Nine of 13 studies examining adapted
      exercise training reported significant improvements in disability, physical
      fitness, physical function, and/or symptomatic and participatory outcomes.
      CONCLUSIONS: There is limited, but promising evidence for the benefits of
      exercise training in persons with MS with severe mobility disability. Considering
      the lack of effective therapeutic strategies for managing long-term disability
      accumulation, exercise training could be considered as an alternative approach.
      Further research is necessary to optimize the prescription and efficacy of
      exercise training for adults with MS with severe mobility disability.

PMID- 28755683
TI  - Sulbutiamine shows promising results in reducing fatigue in patients with
      multiple sclerosis.
AB  - BACKGROUND: Fatigue is the most frequent and often debilitating symptom for
      patients with multiple sclerosis (MS). There are no available effective therapies
      for fatigue associated with MS, and it is unclear whether a successful therapy of
      MS leads to clinical improvement. Sulbutiamine is a lipophilic compound that
      crosses the blood-brain barrier more readily than thiamine and increases the
      levels of thiamine and thiamine phosphate esters in the brain. Whereas several
      clinical trials have demonstrated the beneficial effects of sulbutiamine in
      patients with asthenia, there have been no reports on the effects of sulbutiamine
      on fatigue in patients with MS. OBJECTIVES: Our study was designed to evaluate
      the short-term effects of sulbutiamine on fatigue in patients with MS. METHODS:
      Patients were included if fatigue was one of their three predominant symptoms.
      They were required to have a total score on the Fatigue Impact Scale (FIS) of
      >20, and on the Beck Depression Inventory of <17, and no relapse in the last 3
      months prior to onset of the study. Patients were advised to receive 400mg orally
      of sulbutiamine once daily for two months. The outcome of the study was in the
      changes of FIS. RESULTS: Twenty-six patients with MS (18 females and 8 males)
      were selected. The patients were 18-57 years of age (mean:37,2). The average
      score of Expanded Disability Status Scale (EDSS) of the patients was 2,71. A
      significant number of the subjects who were on some kind of disease modifying
      treatment (DMT) demonstrated obvious improvement in their total FIS scores,
      whereas none of the subjects who were not on any DMT improved (13/23 vs. 0/5).
      The average fatigue score was 77 (SD:30,5) at the baseline and 60,5 (SD:29,7) on
      Day 60, respectively. Sulbutiamine intake resulted in a significant reduction on
      the total score of FIS and on all three subscales assessing physical, cognitive,
      and psychosocial functioning (all p-values < 0,01). There were no serious adverse
      events. CONCLUSIONS: Sulbutiamin appears to be effective in treating fatigue in
      MS; particularly in patients who were on some DMT, but not on those who were not.
      It is well-tolerated by all. This observation may encourage further evaluations
      of the efficacy of sulbutiamine on fatigue in MS.

PMID- 28755684
TI  - Epstein-Barr virus and multiple sclerosis: Updating Pender's hypothesis.
AB  - Substantial epidemiological evidence supports the involvement of the Epstein-Barr
      virus (EBV) in multiple sclerosis (MS). Mechanisms through which EBV may increase
      MS risk are reviewed here. Most individuals contract EBV in early childhood yet
      only develop MS in early adulthood, by which time EBV has been latent for
      decades. When latent, EBV is confined to a minute subset of memory B cells: about
      1000 cells in peripheral blood and 500,000 cells in the lymphoid system, mainly
      in the mouth. Reactivation of EBV in the central nervous system (CNS) has been
      proposed as a cause of MS. Alternatively, EBV may enable the recognition of
      "forbidden" antigens by memory B cells through its presence in this leukocyte
      type, as first proposed by Pender. Though the requirement for B cells in MS
      supports both hypotheses, EBV has not been consistently found in MS lesions, as
      would be expected. EBV episome replication during B cell division is now known to
      be inefficient, resulting in some descendant B cells becoming EBV-free after a
      few dozen divisions. EBV-free memory B cells in the CNS may thus have descended
      from a memory B cell which matured while containing EBV episomes, enabling its B
      cell receptor to recognize "forbidden" MS-causing antigens in the CNS, even if
      EBV is absent from this site.

PMID- 28755685
TI  - Editors' Welcome.

PMID- 28755688
TI  - Differential physiological effects of neonicotinoid insecticides on honey bees: A
      comparison between Apis mellifera and Apis cerana.
AB  - Acute toxicities (LD50s) of imidacloprid and clothianidin to Apis mellifera and
      A. cerana were investigated. Changing patterns of immune-related gene expressions
      and the activities of four enzymes between the two bee species were compared and
      analyzed after exposure to sublethal doses of insecticides. Results indicated
      that A. cerana was more sensitive to imidacloprid and clothianidin than A.
      mellifera. The acute oral LD50 values of imidacloprid and clothianidin for A.
      mellifera were 8.6 and 2.0ng/bee, respectively, whereas the corresponding values
      for A. cerana were 2.7 and 0.5ng/bee. The two bee species possessed distinct
      abilities to mount innate immune response against neonicotinoids. After 48h of
      imidacloprid treatment, carboxylesterase (CCE), prophenol oxidase (PPO), and
      acetylcholinesterase (AChE) activities were significantly downregulated in A.
      mellifera but were upregulated in A. cerana. Glutathione-S-transferase (GST)
      activity was significantly elevated in A. mellifera at 48h after exposure to
      imidacloprid, but no significant change was observed in A. cerana. AChE was
      downregulated in both bee species at three different time points during
      clothianidin exposure, and GST activities were upregulated in both species
      exposed to clothianidin. Different patterns of immune-related gene expression and
      enzymatic activities implied distinct detoxification and immune responses of A.
      cerana and A. mellifera to imidacloprid and clothianidin.

PMID- 28755689
TI  - Display of B. pumilus chitinase on the surface of B. subtilis spore as a
      potential biopesticide.
AB  - BACKGROUND: Chitinases can inhibit the growth of many fungal diseases which are a
      great threat for global agricultural production. Biological control of pathogens
      like fungi, is believed to be one of the best ways to eliminate the adverse
      effects of plant pathogens. To this end, we expressed and displayed a chitinase
      from Bacillus pumilus (ChiS) on the surface of Bacillus subtilis spores, as a
      biocontrol agent. RESULT: ChiS enzyme from B. pumilus was expressed on the spores
      of B. subtilis using CotG as a carrier protein. Immunofluorescence microscopy
      confirmed the expression of ChiS on the surface of the spores. Enzyme activity
      assay showed that the surface displayed ChiS was active and was also able to
      inhibit the growth of Rhizoctonia solani and Trichoderma harzianum fungi. Western
      blot analysis also indicated that CotG-ChiS is partially processed after display.
      Molecular dynamics simulation showed that the stability of the heterologous
      protein was decreased after fusion. CONCLUSION: ChiS was successfully displayed
      on the surface of Bacillus spores by fusion to the CotG, one of the main spore
      coat proteins. In-vitro experiments showed that the displayed enzyme was
      effective in growth inhibition of R. solani and T. harzianum fungi.

PMID- 28755690
TI  - Anti-TMV activity and functional mechanisms of two sesquiterpenoids isolated from
      Tithonia diversifolia.
AB  - Unlike chemical pesticides, antiviral plants are biodegradable, replenishable and
      safe. In this study, 14 sesquiterpene compounds from Tithonia diversifolia were
      tested for their activities against Tobacco mosaic virus (TMV) using the half
      leaf method. Tagitinin C (Ses-2) and 1beta-methoxydiversifolin-3-0-methyl ether
      (Ses-5) were found to have in vivo curative activities of 62.86% and 60.27%
      respectively, at concentrations of 100MUg/mL, respectively. In contrast, the in
      vivo curative inhibition rate of control agent ningnanmycin was 52.48%. Indirect
      enzyme-linked immunosorbent assay (ID-ELISA) also verified Ses-2 and Ses-5 had
      higher inhibition activities than the control agent ningnanmycin. Additionally,
      qRT-PCR showed that both Ses-2 and Ses-5 can partly inhibit the expression of CP
      and RdRp, two genes that play key roles in TMV infection. When TMV started to
      systemically spread, Ses-2 inhibited CP expression while Ses-5 inhibited RdRp
      expression. These results suggest that the two bio-agents have anti-TMV
      activities and may be used as bio-pesticides to control the plant virus.

PMID- 28755691
TI  - Chlorogenic acid is a fungicide active against phytopathogenic fungi.
AB  - Plants synthesize diverse types of secondary metabolites and some of them
      participate in plant protection against pathogen attack. These compounds are
      biodegradable and renewable alternatives, which may be envisaged for the control
      of plant pests and diseases. Chlorogenic acid (CGA) is a phenolic secondary
      metabolite which accumulates in diverse plant tissues and can be found in several
      agro-industrial by-products and waste. The aim of this work was to determine
      whether CGA could control the growth of various plant pathogenic fungi, gaining
      insight into its mechanism of action. Microscopic analysis showed the complete
      inhibition of spore germination or reduction of mycelial growth for Sclerotinia
      sclerotiorum, Fusarium solani, Verticillium dahliae, Botrytis cinerea and
      Cercospora sojina. CGA concentrations that did not completely abolish spore
      germination were able to produce a partial inhibition of mycelial growth.
      Viability tests and vital dye staining demonstrate that CGA induces fungal cell
      lysis. Its fungicidal activity involves an early membrane permeabilization of the
      spores. These results show the antifungal activity of CGA against phytopathogenic
      fungi relevant in horticulture and agriculture highlighting the potential of CGA
      enriched wastes and by-products to be used as biofungicides.

PMID- 28755692
TI  - Two distinctive beta subunits are separately involved in two binding sites of
      imidacloprid with different affinities in Locusta migratoria manilensis.
AB  - Due to great diversity of nicotinic acetylcholine receptor (nAChR) subtypes in
      insects, one beta subunit may be contained in numerous nAChR subtypes. In the
      locust Locusta migratoria, a model insect species with agricultural importance,
      the third beta subunits (Locbeta3) was identified in this study, which reveals at
      least three beta subunits in this insect species. Imidacloprid was found to bind
      nAChRs in L. migratoria central nervous system at two sites with different
      affinities, with Kd values of 0.16 and 10.31nM. The specific antisera (L1-1, L2-1
      and L3-1) were raised against fusion proteins at the large cytoplasmic loop of
      Locbeta1, Locbeta2 and Locbeta3 respectively. Specific immunodepletion of
      Locbeta1 with antiserum L1-1 resulted in the selective loss of the low affinity
      binding site for imidacloprid, whereas the immunodepletion of Locbeta3 with L3-1
      caused the selective loss of the high affinity site. Dual immunodepletion with L1
      1 and L3-1 could completely abolish imidacloprid binding. In contrast, the
      immunodepletion of Locbeta2 had no significant effect on the specific
      [3H]imidacloprid binding. Taken together, these data indicated that Locbeta1 and
      Locbeta3 were respectively contained in the low- and high-affinity binding sites
      for imidacloprid in L. migratoria, which is different to the previous finding in
      Nilaparvata lugens that Nlbeta1 was in two binding sites for imidacloprid. The
      involvement of two beta subunits separately in two binding sites may decrease the
      risk of imidacloprid resistance due to putative point mutations in beta subunits
      in L. migratoria.

PMID- 28755693
TI  - Laboratory evaluation on a potential birth control diet for fruit fly sterile
      insect technique (SIT).
AB  - Sterile insect technique (SIT) is one of the most effective fruit fly control
      technologies. Irradiation has been used to sterilize male fruit flies before
      release to the field to compete with the wild males for females. Imagine an
      environmental and cost effective method using a rearing diet that can make
      insects sterile indefinitely, by feeding for 7days before release. This could
      replace costly irradiation process. A potential birth control diet was evaluated
      on fertility, mating, survival, and protein analysis for fruit fly species in
      Hawaii. Insects were continuously fed an agar diet with lufenuron (LFN) for 7d
      after emergence and then switched to a control diet to simulate the actual field
      condition. The influence on egg hatch was dose dependent. With dose of 2-4mg/g in
      the diet, egg hatch from LFN-fed was almost 100% suppressed for 24 experimental
      days if adults of Ceratitia capitate (Widemann), Bactrocera dorsalis (Hendel),
      and B. latifrons (Hendel) continued to feed on LFN diet. B. cucurbitae
      (Coquillett) was not affected by LFN. However, egg hatch from LFN fed B.
      latifrons and B. dorsalis were suppressed for at least 2weeks after switching to
      the control diet at 7d. Egg hatch did not recover >4% up to 24d. Proteome
      analysis revealed that ABD-4 protein was under expressed by 70-83% on LFN fed
      females and males of B. latifrons and B. dorsalis while Pbprp2 protein was
      significantly over expressed by 6-12 fold on LFN fed males only. These two
      proteins were not expressed in C. capitata and B. cucurbitae. Therefore, this
      report focused more on B. latifrons and B. dorsalis. This finding suggested a
      great potential for one alternative to sterilize fruit flies for SIT without
      irradiation.

PMID- 28755694
TI  - Better cold tolerance of Bt-resistant Spodoptera exigua strain and the
      corresponding cold-tolerant mechanism.
AB  - Spodoptera exigua is a secondary target pest of Bt cotton commercialized in
      China. With the continuous adoption of Bt cotton, populations of S. exigua have
      gradually increased. However, the cold tolerance ability of Bt-resistant S.
      exigua and the effect of continuous Bt diet on anti-cold materials are unknown.
      In our study, it was found that Bt-resistant S. exigua (Bt10) developed better
      with shorter larval and pupal duration and higher pupation rate compared to CK at
      the suboptimal low temperature. The supercooling points and freezing points of
      the Bt-resistant S. exigua strain were determined, and body water content and
      anti-cold materials such as total sugar, trehalose and glycogen, glycerol and fat
      were examined to explore the effect of Bt toxin on overwintering and on
      population increase. The results showed that the supercooling point and the
      freezing point of the Bt-resistant S. exigua pupae were both significantly lower
      than that of the Bt-susceptible strain. No difference was found in the body water
      content of pupae and adults between the two strains. Total sugar content of the
      Bt-resistant strain at both the pupal and adult stages was higher than that of
      the susceptible strain at the corresponding stages, and glycogen content of the
      Bt-resistant strain at the larval stage was higher than that of the susceptible
      larval S. exigua. Fat content of the Bt-resistant larvae, pupae and adults was
      for each higher than that of the susceptible strain, but the difference was not
      significant except for that of the 3rd instar larvae. Glycerol content of the Bt
      resistant strain at larval, pupal and adult stages was for each higher than that
      of the corresponding life stages of the susceptible strain. It can be seen that
      more glycerol was accumulated in Bt-resistant S. exigua. The results indicate
      that Bt-resistant S. exigua has better cold tolerance. The contents of the anti
      freeze substances of progeny, especially glycerol, were increased after previous
      generations were continuously fed on Bt protein, which means that the Bt
      resistant secondary target pests could more easily overcome the overwinter season
      and become a source of crop damage the following year.

PMID- 28755695
TI  - Preimaginal exposure to azadirachtin affects food selection and digestive enzymes
      in adults of Drosophila melanogaster (Diptera: Drosophilidae).
AB  - Among the plant derived product, azadirachtin, a neem-based insecticide, is
      exceptional in having a broad range of bioactivity including toxicity, growth,
      development and reproduction effects, repellency and antifeedancy. If
      considerable progress on the physiological and biological activities and
      agricultural application of azadirachtin has been achieved, its exact mechanism
      of action remains uncertain. In this study, we aimed at assessing the lethal and
      sublethal behavioral and physiological effects of azadirachtin on Drosophila
      melanogaster Meigen, 1830 (Diptera: Drosophilidae) as biological model.
      Azadirachtin was applied topically at two doses LD25 (0.28MUg) and LD50 (0.67MUg)
      on early third instar larvae. Results showed that flies preferentially ingested
      control medium rather than azadirachtin-treated medium. Pre-imaginal exposure
      (L3) to azadirachtin increased aversion to this substance suggesting a
      memorability of the learned avoidance. In addition, all tested flies revealed a
      clear preference for solvent odour rather than azadirachtin odour. Moreover,
      azadirachtin treatment decreased significantly the amount of food intake in the
      adults of both sexes. Finally, azadirachtin was found to affect digestive enzyme
      activities in the midgut of flies. Indeed, an inhibition of alpha-amylase,
      chitinase, and protease activities and an increase of lipasic activity were
      noted. These results may reflect interference of azadirachtin with regulation of
      feeding and metabolism, and provide some evidence of a long term antifeedancy and
      delayed effects through developmental stage which may reinforce the insecticidal
      activity of this bioinsecticide.

PMID- 28755696
TI  - Identification and functional analysis of a new glyphosate resistance gene from a
      fungus cDNA library.
AB  - Glyphosate is a widely used broad spectrum herbicide; however, this limits its
      use once crops are planted. If glyphosate-resistant crops are grown, glyphosate
      can be used for weed control in crops. While several glyphosate resistance genes
      are used in commercial glyphosate tolerant crops, there is interest in
      identifying additional genes for glyphosate tolerance. This research constructed
      a high-quality cDNA library form the glyphosate-resistant fungus Aspergillus
      oryzae RIB40 to identify genes that may confer resistance to glyphosate. Using a
      medium containing glyphosate (120mM), we screened several clones from the
      library. Based on a nucleotide sequence analysis, we identified a gene of unknown
      function (GenBank accession number: XM_001826835.2) that encoded a hypothetical
      344-amino acid protein. The gene was named MFS40. Its ORF was amplified to
      construct an expression vector, pGEX-4T-1-MFS40, to express the protein in
      Escherichia coli BL21. The gene conferred glyphosate tolerance to E. coli ER2799
      cells.

PMID- 28755697
TI  - Proteomic and biochemical assays of glutathione-related proteins in susceptible
      and multiple herbicide resistant Avena fatua L.
AB  - Extensive herbicide usage has led to the evolution of resistant weed populations
      that cause substantial crop yield losses and increase production costs. The
      multiple herbicide resistant (MHR) Avena fatua L. populations utilized in this
      study are resistant to members of all selective herbicide families, across five
      modes of action, available for A. fatua control in U.S. small grain production,
      and thus pose significant agronomic and economic threats. Resistance to ALS and
      ACCase inhibitors is not conferred by target site mutations, indicating that non
      target site resistance mechanisms are involved. To investigate the potential
      involvement of glutathione-related enzymes in the MHR phenotype, we used a
      combination of proteomic, biochemical, and immunological approaches to compare
      their constitutive activities in herbicide susceptible (HS1 and HS2) and MHR
      (MHR3 and MHR4) A. fatua plants. Proteomic analysis identified three tau and one
      phi glutathione S-transferases (GSTs) present at higher levels in MHR compared to
      HS plants, while immunoassays revealed elevated levels of lambda, phi, and tau
      GSTs. GST specific activity towards 1-chloro-2,4-dinitrobenzene was 1.2-fold
      higher in MHR4 than in HS1 plants and 1.3- and 1.2-fold higher in MHR3 than in
      HS1 and HS2 plants, respectively. However, GST specific activities towards
      fenoxaprop-P-ethyl and imazamethabenz-methyl were not different between untreated
      MHR and HS plants. Dehydroascorbate reductase specific activity was 1.4-fold
      higher in MHR than HS plants. Pretreatment with the GST inhibitor NBD-Cl did not
      affect MHR sensitivity to fenoxaprop-P-ethyl application, while the herbicide
      safener and GST inducer mefenpyr reduced the efficacy of low doses of fenoxaprop
      P-ethyl on MHR4 but not MHR3 plants. Mefenpyr treatment also partially reduced
      the efficacy of thiencarbazone-methyl or mesosulfuron-methyl on MHR3 or MHR4
      plants, respectively. Overall, the GSTs described here are not directly involved
      in enhanced rates of fenoxaprop-P-ethyl or imazamethabenz-methyl metabolism in
      MHR A. fatua. Instead, we propose that the constitutively elevated GST proteins
      and related enzymes in MHR plants are representative of a larger, more global
      suite of abiotic stress-related changes.

PMID- 28755698
TI  - Non-target-site resistance to ALS-inhibiting herbicides in a Sagittaria trifolia
      L. population.
AB  - Sagittaria trifolia L. is one of the most competitive weeds in rice fields in
      northeastern China. The continuous use of acetolactate synthase (ALS)-inhibitors
      has led to the evolution of herbicide resistant S. trifolia. A subpopulation BC1,
      which was derived from the L1 population, was analyzed using DNA sequencing and
      ALS enzyme activity assays and levels of resistance to five ALS-inhibiting
      herbicides was determined. DNA sequencing and ALS enzyme assays revealed no amino
      acid substitutions and no significant differences in enzyme sensitivity between
      susceptible and resistant populations. Whole-plant dose-response experiments
      showed that the BC1 population exhibited different levels of resistance
      (resistance ratios ranging from 2.14 to 51.53) to five ALS herbicides, and the
      addition of malathion (P450 inhibitor) to bensulfuron-methyl, penoxsulam and
      bispyribac-sodium strongly reduced the dry weight accumulation of the BC1
      population compared with the effects of the three herbicides alone. The results
      of the present study demonstrated that the BC1 population has evolved non-target
      site resistance to ALS-inhibiting herbicides.

PMID- 28755699
TI  - Cross-resistance and biochemical mechanisms of resistance to indoxacarb in the
      diamondback moth, Plutella xylostella.
AB  - Indoxacarb belongs to a class of insecticides known as oxadiazines and is the
      first commercialized pyrazoline-type voltage-dependent sodium channel blocker. A
      moderate level of resistance to indoxacarb has evolved in field populations of
      Plutella xylostella from Central China. In the present study, cross-resistance,
      resistance stability and metabolic mechanisms of indoxacarb resistance were
      investigated in this moth species. A P. xylostella strain with a high level of
      resistance to indoxacarb was obtained through continuous selection in the
      laboratory. The strain showed cross-resistance to metaflumizone, beta
      cypermethrin and chlorfenapyr, but no resistance to cyantraniliprole,
      chlorantraniliprole, abamectin, chlorfluazuron, spinosad and diafenthiuron
      compared with the susceptible strain. Synergism tests revealed that piperonyl
      butoxide (PBO) (synergistic ratio, SR=7.8) and diethyl maleate (DEF) (SR=3.5) had
      considerable synergistic effects on indoxacarb toxicity in the resistant strain
      (F58). Enzyme activity data showed there was an approximate 5.8-fold different in
      glutathione S-transferase (GST) and a 6.8-fold different in cytochrome P450
      monooxygenase between the resistant strain (F58) and susceptible strain,
      suggesting that the increased activity of these two enzymes is likely the main
      detoxification mechanism responsible for the species' resistance to indoxacarb.
      These results will be helpful for insecticide resistance management strategies to
      delay the development of indoxacarb resistance in fields.

PMID- 28755700
TI  - Effects of rosemary, thyme and lemongrass oils and their major constituents on
      detoxifying enzyme activity and insecticidal activity in Trichoplusia ni.
AB  - Although there have been many reports on the synergistic interactions among the
      major constituents of plant essential oils regarding insecticidal activity, their
      underlying mechanism of synergy is poorly understood. In our previous studies, we
      found each of the two most abundant constituents of rosemary (Rosmarinus
      officinalis L.), thyme (Thymus vulgaris L.) and lemongrass (Cymbopogon citratus
      Stapf.) essential oils can be synergistic against the larvae of the cabbage
      looper, Trichoplusia ni at their natural proportion or equivalent blending
      ratios. In the present study, we investigated whether the enhanced toxicity
      between the major constituents could be the result of inhibited enzyme activity
      of cytochrome P450s, general esterases or glutathione S-transferases which are
      highly related to the development of insecticide resistance. Overall, although
      some combinations showed mild inhibitory activity, at least for these essential
      oils and their major constituents, inhibition of detoxication enzyme activity is
      unlikely to be a direct cause of increased toxicity in the cabbage looper. The
      results point to other factors, such as multiple modes-of-action or enhanced
      penetration through the cuticular layer, playing important roles in the elevated
      insecticidal activity. Moreover, application of enzyme inhibitors sometimes
      resulted in decreased activity when mixed with the target compounds, but these
      antagonistic interactions disappeared when they were applied separately,
      suggesting that the enzyme inhibitors can sometimes influence the penetrations of
      toxicants.

PMID- 28755701
TI  - Effects of oil extracts of Eupatorium adenophorum on Phytophthora capsici and
      other plant pathogenic fungi in vitro.
AB  - The antifungal activity of oils extracted from Eupatorium adenophorum was tested
      against five phytopathogens in vitro. Oil extracts inhibited the mycelial growth
      of Phytophthora capsici which causes phytophthora blight in pepper. The minimum
      inhibitory concentration of oils against P. capsici was 500MUg/ml after 7days
      incubation. At the ultrastructural level, oil extracts caused complete
      disorganization of intracellular organelles, cytoplasm depletion, disruption of
      cytoplasmic membranes and the cell wall. Membrane permeability increased with the
      increasing concentration of oil extracts. These results suggested that these oil
      extracts exhibited multiple modes of action including disruption of the cell
      membrane system. Furthermore, oil extracts combined with synthetic fungicides
      synergistically inhibited mycelial growth of P. capsici, which creates the
      possibility of reducing fungicide concentration needed to successfully control
      phytophthora blight in commercial pepper production. This study's use of multiple
      methods of analysis has increased our understanding of the mode of action of E.
      adenophorum oil extracts against P. capsici.

PMID- 28755702
TI  - Mitochondria response to camptothecin and hydroxycamptothecine-induced apoptosis
      in Spodoptera exigua cells.
AB  - Camptothecin (CPT), a natural alkaloid extracted from Camptotheca acuminata
      Decne, exhibits potential insecticidal activities against various insect species.
      Our previous studies have showed that CPTs induced apoptosis in Spodoptera exigua
      Hubner cell line which is mediated preliminarily by the mitochondrial pathway. In
      this study, changes of mitochondrial morphologic and function were investigated
      to characterize mitochondrial responses in CPTs induced apoptosis. After
      incubation IOZCAS-Spex-II cells with CPT and HCPT, mitochondria exhibited obvious
      changes in the size, morphology and distribution, and ultrastructural alterations
      characterized by disruption of cristae and membrane. The typical characteristics
      of apoptosis, including chromatin condensation, nucleus shrivels, and cytoplasmic
      vacuoles were found. CPT and HCPT induced IOZCAS-Spex-II cell apoptosis
      accompanied with increased dramatically cytosolic Ca2+ and reduced mitochondrial
      membrane potential in the dose and time-dependent pattern. Cytochrome c release
      induced by CPT and HCPT was partially reduced in the presence of CsA, which
      suggested that the opening of mitochondrial permeability transition pore. Taken
      together, these results suggested the role of mitochondria in regulation of
      insect cell apoptosis, which provided the basic information for illustrating the
      apoptosis pathway in insects and for using reasonably CPTs to control insect
      pests.

PMID- 28755703
TI  - Through the Glass Brightly: Pathology Review in the Multidisciplinary Setting.
AB  - Hospital-centered academic surgical pathologists are essential members of
      multidisciplinary head and neck tumor boards. A working, multidisciplinary head
      and neck tumor board is composed of many dedicated professionals who contribute
      their individual pieces of patient data. This weekly congregation of head and
      neck specialists results in a special, concerted, and dynamic process of data
      integration into a holistic matrix view of the patients. Despite all the
      technological advances in communication, the fundamentals of human interactions
      still apply: there is no better substitute for a regular, working,
      multidisciplinary head and neck tumor board.

PMID- 28755704
TI  - It Takes Two: One Resects, One Reconstructs.
AB  - Care of patients with advanced head and neck cancer is a multidisciplinary effort
      through all phases of care. Head and neck cancer surgery involves balancing
      oncologic control, functional preservation, and aesthetics. Given the advances in
      free tissue reconstruction, the majority of defects can be reconstructed using
      free tissue transfer flaps. A 2-team approach allows for early, continual
      communication and meticulous operative planning. Operations can be combined into
      a single effort. This approach maximizes efficiency and enables multidisciplinary
      collaboration for comprehensive surgical treatment. We present our experience and
      an outline of how responsibilities between the ablative and reconstructive teams
      are shared.

PMID- 28755705
TI  - Systemic Treatment for Squamous Cell Carcinoma of the Head and Neck.
AB  - In patients with locally advanced squamous cell cancer of the head and neck, a
      multimodality treatment approach is recommended. The addition of platinum-based
      systemic therapy concurrently with radiation has been shown to be superior to
      radiation alone and is considered standard therapy for locally advanced disease.
      No study has shown superiority of induction therapy followed by chemoradiotherapy
      versus chemoradiotherapy alone. In the adjuvant setting only patients with nodal
      extracapsular extension or positive margins seem to benefit from
      chemoradiotherapy versus radiotherapy alone. In the recurrent or metastatic
      setting, systemic treatment with chemotherapy is palliative. A subset of patients
      treated with PD-1 immunotherapy may achieve durable responses.

PMID- 28755706
TI  - Psychosocial Distress and Distress Screening in Multidisciplinary Head and Neck
      Cancer Treatment.
AB  - Psychosocial distress screening (DS) for cancer and head and neck cancer (HNC)
      patients is rapidly becoming the standard of care. DS is of particular importance
      for patients with HNC, given their heightened incidence of distress, depression,
      anxiety, suicide, quality of life impacts, and negative medical outcomes. In the
      absence of DS, distress is frequently missed in oncology settings. However, when
      identified, distress is highly responsive to treatment, with cognitive behavioral
      and behavioral medicine interventions demonstrating evidence of efficacy.
      Multidisciplinary HNC teams are uniquely positioned to implement effective DS
      programs and treatment tailored to HNC patients' psychological and medical
      vulnerabilities.

PMID- 28755707
TI  - Survivorship: Morbidity, Mortality, Malignancy.
AB  - Survivorship encompasses the entire therapeutic, psychosocial, functional, and
      financial experience of living with and through a cancer diagnosis. The period of
      survivorship starts on the day of the cancer diagnosis and lasts until the end of
      the survivor's life, regardless of the cause of death. The National Cancer
      Institute's Office of Cancer Survivorship expands the term "survivor" to include,
      importantly, caregivers, family, and friends close to the survivor who also live
      through this period.

PMID- 28755709
TI  - More than Just Mitoses: Complete Care of the Patient with Head and Neck Cancer.

PMID- 28755708
TI  - Immunotherapy: Who Is Eligible?
AB  - Recurrent and/or metastatic head and neck cancer portends a poor prognosis with
      traditional treatments, but current immunotherapy with immune checkpoint
      inhibitors has the potential to improve these clinical outcomes. This review
      focuses on the major breakthroughs that have led to the current understanding of
      immunotherapy in head and neck cancer as well as the future direction of the
      field. Ultimately, this understanding will guide clinicians on the selection of
      patients with head and neck cancer and practical considerations before starting
      immunotherapy.

PMID- 28755710
TI  - Multidisciplinary Approach to Head and Neck Cancer.

PMID- 28755711
TI  - Opportunities before You.

PMID- 28755712
TI  - Biogeography of bloom-forming microcystin producing and non-toxigenic populations
      of Dolichospermum lemmermannii (Cyanobacteria).
AB  - In the last decades, the cyanobacterium Dolichospermum lemmermannii showed an
      increasing spread to Southern Europe, raising serious concerns due to its ability
      to produce cyanotoxins. The widening of its geographic distribution and the
      observation of strains showing high optimum temperature underline its ecological
      heterogeneity, suggesting the existence of different ecotypes. To investigate its
      biogeography, new isolates from different European water bodies, together with
      strains maintained by the Norwegian Institute for Water Research Culture
      Collection of Algae, were genetically characterised for the 16S rRNA gene and
      compared with strains obtained from public repositories. Geographic distance
      highly influenced the differentiation of genotypes, further suggesting the
      concurrent role of geographic isolation, physical barriers and environmental
      factors in promoting the establishment of phylogenetic lineages adapted to
      specific habitats. Differences among populations were also examined by
      morphological analysis and evaluating the toxic potential of single strains,
      which revealed the exclusive ability of North European strains to produce
      microcystins, whereas the populations in Southern Europe tested negative for a
      wide range of cyanotoxins. The high dispersion ability and the existence of toxic
      genotypes indicate the possible spread of harmful blooms in other temperate
      regions.

PMID- 28755713
TI  - Taxonomic assignment of the benthic toxigenic dinoflagellate Gambierdiscus sp.
      type 6 as Gambierdiscus balechii (Dinophyceae), including its distribution and
      ciguatoxicity.
AB  - Recent molecular phylogenetic studies of Gambierdiscus species flagged several
      new species and genotypes, thus leading to revitalizing its systematics. The
      inter-relationships of clades revealed by the primary sequence information of
      nuclear ribosomal genes (rDNA), however, can sometimes be equivocal, and
      therefore, in this study, the taxonomic status of a ribotype, Gambierdiscus sp.
      type 6, was evaluated using specimens collected from the original locality,
      Marakei Island, Republic of Kiribati; and specimens found in Rawa Island,
      Peninsular Malaysia, were further used for comparison. Morphologically, the
      ribotype cells resembled G. scabrosus, G. belizeanus, G. balechii, G. cheloniae
      and G. lapillus in thecal ornamentation, where the thecal surfaces are reticulate
      foveated, but differed from G. scabrosus by its hatchet-shaped Plate 2', and G.
      belizeanus by the asymmetrical Plate 3'. To identify the phylogenetic
      relationship of this ribotype, a large dataset of the large subunit (LSU) and
      small subunit (SSU) rDNAs were compiled, and performed comprehensive analyses,
      using Bayesian-inference, maximum-parsimony, and maximum-likelihood, for the
      latter two incorporating the sequence-structure information of the SSU rDNA. Both
      the LSU and SSU rDNA phylogenetic trees displayed an identical topology and
      supported the hypothesis that the relationship between Gambierdiscus sp. type 6
      and G. balechii was monophyletic. As a result, the taxonomic status of
      Gambierdiscus sp. type 6 was revised, and assigned as Gambierdiscus balechii.
      Toxicity analysis using neuroblastoma N2A assay confirmed that the Central
      Pacific strains were toxic, ranging from 1.1 to 19.9 fg P-CTX-1 eq cell-1, but no
      toxicity was detected in a Western Pacific strain. This suggested that the
      species might be one of the species contributing to the high incidence rate of
      ciguatera fish poisoning in Marakei Island.

PMID- 28755714
TI  - Pseudo-nitzschia simulans sp. nov. (Bacillariophyceae), the first domoic acid
      producer from Chinese waters.
AB  - The genus Pseudo-nitzschia has attracted attention because of production of the
      toxin, domoic acid (DA), causing Amnesic Shellfish Poisoning (ASP). Pseudo
      nitzschia blooms occur frequently in Chinese coastal waters, and DA has been
      detected in several marine organisms, but so far no Pseudo-nitzschia strains from
      Chinese waters have been shown to produce DA. In this study, monoclonal Pseudo
      nitzschia strains were established from Chinese coastal waters and examined using
      light microscopy, electron microscopy and molecular markers. Five strains,
      sharing distinct morphological and molecular features differentiating them from
      other Pseudo-nitzschia species, represent a new species, Pseudo-nitzschia
      simulans sp. nov. Morphologically, the taxon belongs to the P.
      pseudodelicatissima group, cells possessing a central nodule and each stria
      comprising one row of poroids. The new species is characterized by the poroid
      structure, which typically comprises two sectors, each sector located near
      opposite margins of the poroid. The production of DA was examined by liquid
      chromatography tandem mass spectrometry (LC-MS/MS) analyses of cells in
      stationary growth phase. Domoic acid was detected in one of the five strains,
      with concentrations around 1.05-1.54 fg cell-1. This is the first toxigenic
      diatom species reported from Chinese waters.

PMID- 28755715
TI  - Mathematical modeling of Microcystis aeruginosa growth and [D-Leu1] microcystin
      LR production in culture media at different temperatures.
AB  - The effect of temperature (26 degrees C, 28 degrees C, 30 degrees C and 35
      degrees C) on the growth of native CAAT-3-2005 Microcystis aeruginosa and the
      production of Chlorophyll-a (Chl-a) and Microcystin-LR (MC-LR) were examined
      through laboratory studies. Kinetic parameters such as specific growth rate (MU),
      lag phase duration (LPD) and maximum population density (MPD) were determined by
      fitting the modified Gompertz equation to the M. aeruginosa strain cell count
      (cellsmL-1). A 4.8-fold increase in MU values and a 10.8-fold decrease in the LPD
      values were found for M. aeruginosa growth when the temperature changed from 15
      degrees C to 35 degrees C. The activation energy of the specific growth rate
      (EMU) and of the adaptation rate (E1/LPD) were significantly correlated
      (R2=0.86). The cardinal temperatures estimated by the modified Ratkowsky model
      were minimum temperature=8.58+/-2.34 degrees C, maximum temperature=45.04+/-1.35
      degrees C and optimum temperature=33.39+/-0.55 degrees C. Maximum MC-LR
      production decreased 9.5-fold when the temperature was increased from 26 degrees
      C to 35 degrees C. The maximum production values were obtained at 26 degrees C
      and the maximum depletion rate of intracellular MC-LR was observed at 30-35
      degrees C. The MC-LR cell quota was higher at 26 and 28 degrees C (83 and
      80fgcell-1, respectively) and the MC-LR Chl-a quota was similar at all the
      different temperatures (0.5-1.5fgng-1). The Gompertz equation and dynamic model
      were found to be the most appropriate approaches to calculate M. aeruginosa
      growth and production of MC-LR, respectively. Given that toxin production
      decreased with increasing temperatures but growth increased, this study
      demonstrates that growth and toxin production processes are uncoupled in M.
      aeruginosa. These data and models may be useful to predict M. aeruginosa bloom
      formation in the environment.

PMID- 28755716
TI  - "Canary Islands (NE Atlantic) as a biodiversity 'hotspot' of Gambierdiscus:
      Implications for future trends of ciguatera in the area".
AB  - In the present study the geographical distribution, abundance and composition of
      Gambierdiscus was described over a 600km longitudinal scale in the Canary
      Islands. Samples for cell counts, isolation and identification of Gambierdiscus
      were obtained from five islands (El Hierro, Tenerife, Gran Canaria, Fuerteventura
      and Lanzarote). Average densities of Gambierdiscus spp. between 0 and 2200cellsg
      1 blot dry weight of macrophyte were recorded. Morphological (light microscopy
      and SEM techniques) and molecular analyses (LSU and SSU rDNA sequencing of
      cultures and single cells from the field) of Gambierdiscus was performed. Five
      Gambierdiscus species (G. australes, G. caribaeus, G. carolinianus, G.
      excentricus and G. silvae), together with a new putative species (Gambierdiscus
      ribotype 3) were identified. These results suggest that some cases of CFP in the
      region could be associated with the accumulation of ciguatoxins in the marine
      food web acquired from local populations of Gambierdiscus. This unexpected high
      diversity of Gambierdiscus species in an area which a priori is not under risk of
      ciguatera, hints at an ancient settlement of Gambierdiscus populations, likely
      favored by warmer climate conditions in the Miocene Epoch (when oldest current
      Canary Islands were created), in contrast with cooler present ones. Currently,
      warming trends associated with climate change could contribute to extend
      favorable environmental conditions in the area for Gambierdiscus growth
      especially during winter months.

PMID- 28755718
TI  - Comparative proteomic studies of a Scrippsiella acuminata bloom with its
      laboratory-grown culture using a 15N-metabolic labeling approach.
AB  - Comparative proteomic analysis was carried out using cells isolated from a
      natural bloom of Scrippsiella acuminata (formerly Scrippsiella trochoidea) in the
      early bloom (EB) and late bloom (LB) stages as well as with laboratory-grown
      cultures of cells isolated from the bloom in early growth (EG) and late growth
      (LG) stages. For quantitative proteomics, LG cells were grown for 20 generations
      in the presence of 15N as a reference (i.e. common denominator) for all
      comparison. In comparisons with early growth laboratory grown cells (EG/LG),
      nearly 64% of proteins identified had similar abundance levels, with the
      remaining 36% mostly more abundant in EG cells. Calvin cycle, amino acid
      metabolism, chlorophyll biosynthesis and transcription/translation were among the
      up-regulated processes. Cells from the early bloom (EB/LG) had a greater
      abundance of transporters and enzymes related to light harvesting and oxidative
      phosphorylation, while the abundance of these proteins decreased in late bloom
      cells (LB/LG). All natural bloom samples showed either constant or lower
      abundance levels of enzymes involved in sugar synthesis and glycolytic pathways
      compared to laboratory grown cells. Our results represent the first examination
      of the proteomic changes in the development of a natural dinoflagellate bloom.
      Importantly, our results demonstrate that the proteome of cells grown in the
      laboratory is distinctively different from cells in a natural bloom.

PMID- 28755717
TI  - A method for examining temporal changes in cyanobacterial harmful algal bloom
      spatial extent using satellite remote sensing.
AB  - Cyanobacterial harmful algal blooms (CyanoHAB) are thought to be increasing
      globally over the past few decades, but relatively little quantitative
      information is available about the spatial extent of blooms. Satellite remote
      sensing provides a potential technology for identifying cyanoHABs in multiple
      water bodies and across geo-political boundaries. An assessment method was
      developed using MEdium Resolution Imaging Spectrometer (MERIS) imagery to
      quantify cyanoHAB surface area extent, transferable to different spatial areas,
      in Florida, Ohio, and California for the test period of 2008 to 2012. Temporal
      assessment was used to evaluate changes in satellite resolvable inland
      waterbodies for each state of interest. To further assess cyanoHAB risk within
      the states, the World Health Organization's (WHO) recreational guidance level
      thresholds were used to categorize surface area of cyanoHABs into three risk
      categories: low, moderate, and high-risk bloom area. Results showed that in
      Florida, the area of cyanoHABs increased largely due to observed increases in
      high-risk bloom area. California exhibited a slight decrease in cyanoHAB extent,
      primarily attributed to decreases in Northern California. In Ohio (excluding Lake
      Erie), little change in cyanoHAB surface area was observed. This study uses
      satellite remote sensing to quantify changes in inland cyanoHAB surface area
      across numerous water bodies within an entire state. The temporal assessment
      method developed here will be relevant into the future as it is transferable to
      the Ocean Land Colour Instrument (OLCI) on Sentinel-3A/3B missions.

PMID- 28755719
TI  - Understanding the blob bloom: Warming increases toxicity and abundance of the
      harmful bloom diatom Pseudo-nitzschia in California coastal waters.
AB  - The toxic diatom genus Pseudo-nitzschia produces environmentally damaging harmful
      algal blooms (HABs) along the U.S. west coast and elsewhere, and a recent ocean
      warming event coincided with toxic blooms of record extent. This study examined
      the effects of temperature on growth, domoic acid toxin production, and
      competitive dominance of two Pseudo-nitzschia species from Southern California.
      Growth rates of cultured P. australis were maximal at 23 degrees C (~0.8d-1),
      similar to the maximum temperature recorded during the 2014-2015 warming anomaly,
      and decreased to ~0.1 d-1 by 30 degrees C. In contrast, cellular domoic acid
      concentrations only became detectable at 23 degrees C, and increased to maximum
      levels at 30 degrees C. In two incubation experiments using natural Southern
      California phytoplankton communities, warming also increased the relative
      abundance of another potentially toxic local species, P. delicatissima. These
      results suggest that both the toxicity and the competitive success of particular
      Pseudo-nitzschia spp. can be positively correlated with temperature, and
      therefore there is a need to determine whether harmful blooms of this diatom
      genus may be increasingly prevalent in a warmer future coastal ocean.

PMID- 28755720
TI  - Global and local factors driving the phenology of Alexandrium minutum (Halim)
      blooms and its toxicity.
AB  - The dinoflagellate Alexandrium minutum is a toxic bloom-forming species
      distributed worldwide. The mechanisms driving and promoting the species blooms
      and their toxicity are studied and presented here. Most previously published work
      focuses on local and/or short-term scales. In this study, a broad temporal and
      spatial approach is addressed using time series covering several sites over
      several years and combining environmental variables and A. minutum abundances
      from the French English Channel - Atlantic coasts. Data were explored by means of
      phenology and threshold analysis. The A. minutum bloom characteristics are
      defined. Only one bloom per year is measured and it may reach more than a million
      of cells L-1. Bloom period extends from April to October and the bloom length
      ranges from two weeks to six months. In the ecosystems studied, water temperature
      and river flow, as regional and local factors respectively, are the main
      environmental drivers influencing the magnitude, growth rate and length of the
      blooms. Bloom toxicity is linked to the bloom maximum abundance and river flow.
      This work provides new knowledge for further managing tools for A. minutum blooms
      in the ecosystems studied.

PMID- 28755721
TI  - Multiannual Chattonella subsalsa Biecheler (Raphidophyceae) blooms in a
      Mediterranean lagoon (Santa Giusta Lagoon, Sardinia Island, Italy).
AB  - Recurrent blooms of Chattonella subsalsa (Raphidophyceae) were associated with
      fish kills in Santa Giusta Lagoon (Mediterranean Sea). This study investigated
      the population dynamics of C. subsalsa and its relationship with environmental
      and meteorological conditions, using multiannual ecological data (1990-2016). In
      addition, for the first time, this study examined the presence of C. subsalsa
      cysts in lagoon sediments. The species was first detected in Santa Giusta Lagoon
      in July 1994. Bloom events coinciding with fish kills were recorded in 1994,
      1998, 1999, and 2010. The timing and dynamics of C. subsalsa blooms and fish
      kills varied over the examined period. Presence of C. subsalsa was strongly
      influenced by temperature, especially in the early years of the series (1990
      2002). Temperature control may have been lesser important in the more recent
      years, when higher temperature may have generated continuative suitable
      conditions for C. subsalsa affirmation, especially in July. Thus, the variations
      in the availability of food (via autotrophy and/or mixotrophy) could be one of
      the control keys on the proliferation of this species in the future in SG. Cysts
      of C. subsalsa were present in lagoon sediments at abundances ranging 200
      2000cystsg-1 wet sediment. This study is among a few that have examined C.
      subsalsa population dynamics and bloom events in the field over a long time
      period. Findings from this study contribute to a better understanding of C.
      subsalsa bloom development, by identifying environmental and meteorological
      variables that may promote blooms of this species in the Santa Giusta Lagoon.

PMID- 28755722
TI  - Molecular mechanism of glucose-6-phosphate utilization in the dinoflagellate
      Karenia mikimotoi.
AB  - Phosphorus (P) is an essential nutrient for marine phytoplankton as for other
      living organisms, and the preferred form, dissolved inorganic phosphate (DIP), is
      often quickly depleted in the sunlit layer of the ocean. Phytoplankton have
      developed mechanisms to utilize organic forms of P (DOP). Hydrolysis of DOP to
      release DIP by alkaline phosphatase is believed to be the most common mechanism
      of DOP utilization. Little effort has been made, however, to understand other
      potential molecular mechanisms of utilizing different types of DOP. This study
      investigated the bioavailability of glucose-6-phosphate (G6P) and its underlying
      molecular mechanism in the dinoflagellate Karenia mikimotoi. Suppression
      Subtraction Hybridization (SSH) was used to identify genes up- and down-regulated
      during G6P utilization compared to DIP condition. The results showed that G6P
      supported the growth and yield of K. mikimotoi as efficiently as DIP. Neither DIP
      release nor AP activity was detected in the cultures grown in G6P medium,
      however, suggesting direct uptake of G6P. SSH analysis and RT-qPCR results showed
      evidence of metabolic modifications, particularly that mitochondrial ATP synthase
      f1gamma subunit and thioredoxin reductase were up-regulated while diphosphatase
      and pyrophosphatase were down-regulated in the G6P cultures. All the results
      indicate that K. mikimotoi has developed a mechanism other than alkaline
      phosphatase to utilize G6P.

PMID- 28755723
TI  - Review: a meta-analysis comparing cell-division and cell-adhesion in Microcystis
      colony formation.
AB  - The freshwater cyanobacterium Microcystis is a nuisance species. It forms large
      blooms on the water surface and overwhelmingly dominates the ecosystem through
      the formation of colonies from single cells surrounded by mucilage; however, the
      mechanism of colony formation is poorly understood. Two mechanisms of Microcystis
      colony formation have been proposed: cell-division, where cells remain attached
      after binary fission; and cell-adhesion, where single cells stick together. This
      paper examined the published literature on Microcystis colony formation to
      clarify the mechanism of colony formation and its relationship to environmental
      drivers. This meta-analysis showed that in laboratory experiments, colony
      formation by cell-division was mainly induced by zooplankton filtrate, high Pb2+
      concentrations, the presence of the cyanobacterium Cylindrospermopsis
      raciborskii, heterotrophic bacteria, and low temperature and low light
      intensities. Alternatively, colony formation by cell-adhesion was mainly induced
      by zooplankton grazing, high Ca2+ concentrations, and microcystins. Therefore,
      colony formation by cell-division appears to be a slower process and to occur
      under an environmental stress factor, while cell-adhesion occurs more quickly to
      an environmental threat. Applying the criteria to the different morphospecies of
      Microcystis, it was found that under natural conditions M. ichthyoblabe colonies
      formed predominantly through cell-division, whereas M. wesenbergii colonies
      formed predominantly through cell-adhesion. This study provides new insights into
      the mechanisms and environmental drivers of colony formation by Microcystis.

PMID- 28755724
TI  - Effects of elevated CO2 on phytoplankton community biomass and species
      composition during a spring Phaeocystis spp. bloom in the western English
      Channel.
AB  - A 21-year time series of phytoplankton community structure was analysed in
      relation to Phaeocystis spp. to elucidate its contribution to the annual carbon
      budget at station L4 in the western English Channel (WEC). Between 1993-2014
      Phaeocystis spp. contributed ~4.6% of the annual phytoplankton carbon and during
      the March - May spring bloom, the mean Phaeocystis spp. biomass constituted 17%
      with a maximal contribution of 47% in 2001. Upper maximal weekly values above the
      time series mean ranged from 63 to 82% of the total phytoplankton carbon (~42
      137mg carbon (C)m-3) with significant inter-annual variability in Phaeocystis
      spp. Maximal biomass usually occurred by the end of April, although in some cases
      as early as mid-April (2007) and as late as late May (2013). The effects of
      elevated pCO2 on the Phaeocystis spp. spring bloom were investigated during a
      fifteen-day semi-continuous microcosm experiment. The phytoplankton community
      biomass was estimated at ~160mgCm-3 and was dominated by nanophytoplankton (40%,
      excluding Phaeocystis spp.), Phaeocystis spp. (30%) and cryptophytes (12%). The
      smaller fraction of the community biomass comprised picophytoplankton (9%),
      coccolithophores (3%), Synechococcus (3%), dinoflagellates (1.5%), ciliates (1%)
      and diatoms (0.5%). Over the experimental period, total biomass increased
      significantly by 90% to ~305mgCm-3 in the high CO2 treatment while the ambient
      pCO2 control showed no net gains. Phaeocystis spp. exhibited the greatest
      response to the high CO2 treatment, increasing by 330%, from ~50mgCm-3 to over
      200mgCm-3 and contributing ~70% of the total biomass. Taken together, the results
      of our microcosm experiment and analysis of the time series suggest that a future
      high CO2 scenario may favour dominance of Phaeocystis spp. during the spring
      bloom. This has significant implications for the formation of hypoxic zones and
      the alteration of food web structure including inhibitory feeding effects and
      lowered fecundity in many copepod species.

PMID- 28755725
TI  - Why Do Clinicians Need to Study the History of Medicine and Why Should This
      Journal Publish Articles About It?

PMID- 28755726
TI  - The Underappreciated Doctors of The American Civil Rights Movement. Part I:
      Theodore Roosevelt Mason Howard, MD.
AB  - During the fight to end segregation in the United States, most of the 25 or so
      black physicians who had not already left Mississippi took risks to become active
      in civil rights locally and nationally. One of the first was T.R.M. Howard, MD,
      whose life story is both an encouragement and warning for today's physicians.
      Howard, the protege of a white Adventist physician, became active in civil rights
      during medical school. While serving as chief surgeon of the all-black hospital
      in Mississippi, he formed his own civil rights organization in 1951 and worked to
      solve the shootings of 2 of its members, George Lee and Gus Courts, and the
      murder of Emmett Till in 1955. His reports of these events and collaborations
      with other civil rights icons helped trigger the modern civil rights movement. At
      the same time, he became a nationally known proponent of abortion rights and then
      fled to Chicago in 1956, after arming his Delta mansion with long guns and a
      Thompson machine gun. Howard will be remembered for many things, including his
      activism for the social determinants of health as president of the National
      Medical Association.

PMID- 28755727
TI  - Plasma Antiphospholipid Antibodies Effects on Activated Partial Thromboplastin
      Time Assays.
AB  - BACKGROUND: Activated partial thromboplastin time (aPTT) assays can be affected
      by plasma antiphospholipid antibodies (aPLs), but the degree of the interference
      is not easy to predict. This study aimed to investigate the effects on aPTT assay
      results of different types and combinations of aPLs, including anti-beta2
      glycoprotein I antibodies, anticardiolipin antibodies and lupus anticoagulant.
      MATERIALS AND METHODS: We retrospectively collected clinical information and
      laboratory tests from aPL-positive patients. The potential influence of aPLs on
      aPTT assays was assessed. RESULTS: The survey included 589 aPL-positive patients.
      No significant differences existed in basic characteristics such as sex, age,
      prothrombin time, fibrinogen and alanine aminotransferase among different cases
      with 1, 2 or 3 types of positive-aPL markers (P > 0.05). In 113 patients with
      abnormal aPTT values, multivariable linear regression analysis showed a
      significant correlation between an abnormal degree of aPTT values and dilute
      Russell viper venom time (dRVVT) or silica clotting time (SCT) with a correlation
      coefficient of 0.437 or 0.497 (P < 0.01), whereas age, anticardiolipin antibodies
      immunoglobulin G, anticardiolipin antibodies-immunoglobulin M and anti-beta2
      glycoprotein I antibodies were of no significance (P > 0.05). Among blood samples
      with 3 types of aPLs positivity, the rate of abnormal aPTT detection values was
      55.3%, which was significantly higher than that observed in patients with
      negative, single-positive or double-positive aPL markers (P < 0.05). Patients
      with a moderate to strong dRVVT or SCT had a higher proportion of abnormal aPTT
      assays than did patients with a low dRVVT or SCT (P < 0.05). CONCLUSIONS: When
      abnormal aPTT values are obtained, the influence of aPLs should be considered,
      especially in the presence of a moderate to strong dRVVT or SCT.

PMID- 28755728
TI  - Prognostic Value of Ventricular Wall Motion Score and Global Registry of Acute
      Coronary Events Score in Patients With Acute Myocardial Infarction.
AB  - OBJECTIVE: The aim of this study was to evaluate the prognostic values of
      ventricular wall motion score (WMS) and Global Registry of Acute Coronary Events
      (GRACE) score in patients with acute myocardial infarction (AMI) in a 12-month
      single-center prospective cohort. MATERIALS AND METHODS: Consecutive inpatients
      diagnosed with AMI in the Department of Cardiology of The Second Affiliated
      Hospital of Soochow University from September 2012 through March 2015 were
      enrolled in this study. Echocardiography was issued to all subjects to calculate
      WMS within 24 hours after admission, and GRACE score of each patient was obtained
      simultaneously. During a 12-month follow-up period, all major adverse cardiac
      events (MACE) were recorded. RESULTS: After 12 months of observation, 124 of 635
      patients with AMI developed MACE. The WMS (23.70 +/- 3.80 versus 20.47 +/- 3.25)
      and GRACE score (185.59 +/- 45.16 versus 152.19 +/- 36.51) were significantly
      higher in patients with MACE than those without MACE (P < 0.05). Survival
      analysis using Cox regression revealed that both WMS (95% CI: 1.082-1.184, P <
      0.05) and GRACE score (95% CI: 1.010-1.021, P < 0.05) independently predicted
      MACE. The receiver operating curve curve analysis showed that the area under
      curve of WMS, GRACE score and the combination of WMS and GRACE score were 0.768
      (P < 0.05), 0.718 (P < 0.05) and 0.812 (P < 0.05), respectively. CONCLUSIONS: WMS
      and GRACE score were independent predictors of MACE in patients with AMI in 12
      month follow-up, and the combined application of WMS and GRACE score can
      significantly improve the predictive value.

PMID- 28755729
TI  - Biomarkers in Sepsis: On Target or Off the Mark?

PMID- 28755730
TI  - Is Decreased Mean Platelet Volume in Allergic Airway Diseases Associated With
      Extent of the Inflammation Area?
AB  - OBJECTIVE: The aim of this study was to determine the relationship between mean
      platelet volume (MPV) level and the extent of airway inflammation in allergic
      airway diseases and in subgroups by comparison of inflammatory markers. MATERIALS
      AND METHODS: A retrospective examination was made of 250 patients with allergic
      airway disease in the symptomatic phase, who had been newly diagnosed or who had
      abandoned treatment for at least 6 months. These patients were separated into 3
      groups of asthma without allergic rhinitis (A - AR, n = 107), asthma with
      allergic rhinitis (A + AR, n = 83) and allergic rhinitis without asthma (AR - A,
      n = 60). RESULTS: The MPV values of the study groups were found to be
      significantly lower than those of the control group (P < 0.001). MPV was
      determined to be negatively correlated with white blood cells, neutrophil count,
      platelet count and immunoglobulin E level in the study groups. The lowest MPV
      value was determined in the A + AR group (8.035 +/- 1.05fL), which had the most
      extensive airway involvement, and the highest MPV value was determined in the AR 
      A group (8.109 +/- 1.11fL) with the least airway involvement. MPV level
      sensitivity and the specificity of the best cutoff level were 74.5% and 40.8%,
      respectively. The cutoff level of 8.18fL for MPV level was found to have moderate
      sensitivity and low specificity for predicting pulmonary embolism. CONCLUSIONS:
      The results of this study showed that MPV is lower in allergic airway diseases
      and a negative correlation was determined between MPV and inflammation markers
      but no statistically significant difference was determined between MPV and extent
      of the inflammation area.

PMID- 28755731
TI  - Potential Value of Coagulation Parameters for Suggesting Preeclampsia During the
      Third Trimester of Pregnancy.
AB  - BACKGROUND: Preeclampsia is a relatively common complication of pregnancy and
      considered to be associated with different degrees of coagulation dysfunction.
      This study was developed to evaluate the potential value of coagulation
      parameters for suggesting preeclampsia during the third trimester of pregnancy.
      MATERIALS AND METHODS: Data from 188 healthy pregnant women, 125 patients with
      preeclampsia in the third trimester and 120 age-matched nonpregnant women were
      analyzed. Prothrombin time, prothrombin activity, activated partial
      thromboplastin time, fibrinogen (Fg), antithrombin, platelet count, mean platelet
      volume, platelet distribution width and plateletcrit were tested. RESULTS: All
      parameters, excluding prothrombin time, platelet distribution width and
      plateletcrit, differed significantly between healthy pregnant women and those
      with preeclampsia. Platelet count, antithrombin and Fg were significantly lower
      and mean platelet volume and prothrombin activity were significantly higher in
      patients with preeclampsia (P < 0.001). Among these parameters, the largest area
      under the receiver operating characteristic curve for preeclampsia was 0.872 for
      Fg with an optimal cutoff value of <=2.87g/L (sensitivity = 0.68 and specificity
      = 0.98). For severe preeclampsia, the area under the curve for Fg reached up to
      0.922 with the same optimal cutoff value (sensitivity = 0.84, specificity = 0.98,
      positive predictive value = 0.96 and negative predictive value = 0.93).
      CONCLUSIONS: Fg is a biomarker suggestive of preeclampsia in the third trimester
      of pregnancy, and our data provide a potential cutoff value of Fg <= 2.87g/L for
      screening preeclampsia, especially severe preeclampsia.

PMID- 28755732
TI  - The Urinothorax: A Comprehensive Review With Case Series.
AB  - Urinothorax is an uncommon thoracic complication of genitourinary (GU) tract
      disease, which is most frequently caused by obstructive uropathy, but may also
      occur as a result of iatrogenic or traumatic GU injury. It is underrecognized
      because of a perceived notion as to the rarity of the diagnosis and the absence
      of established diagnostic criteria. Urinothorax is typically described as a
      paucicellular, transudative pleural effusion with a pleural fluid/serum
      creatinine ratio >1.0. It is the only transudate associated with pleural fluid
      acidosis (pH < 7.40). When the pleural fluid analysis demonstrates features of a
      transudate, pH <7.40 and a pleural fluid/serum creatinine ratio >1.0, a confident
      clinical diagnosis of urinothorax can be established. A technetium 99m renal scan
      can be considered a confirmatory test in patients who lack the typical pleural
      fluid analysis features or fail to demonstrate evidence of obstructive uropathy
      that can be identified via conventional radiographic modalities. Management of a
      urinothorax requires a multidisciplinary approach with an emphasis on the
      correction of the underlying GU tract pathology, and once corrected, this often
      leads to a rapid resolution of the pleural effusion.

PMID- 28755733
TI  - Hepatitis C Viral Infection and Porphyria Cutanea Tarda.

PMID- 28755734
TI  - Epigallocatechin-3-Gallate: The Prospective Targeting of Cancer Stem Cells and
      Preventing Metastasis of Chemically-Induced Mammary Cancer in Rats.
AB  - BACKGROUND: Cancer stem cells are a subpopulation of tumor cells that are capable
      of self-renewal, capable of tumor recurrence and metastasis, and in addition are
      resistant to current cancer therapies. Epigallocatechin-3-gallate is a type of
      catechin found in green tea that is known for its powerful chemoprotective
      ability. Hence, this study aimed to investigate the effect of epigallocatechin-3
      gallate on 7, 12 dimethylbenzanthracene-induced tumor metastasis, angiogenesis
      and cancer stem cells. MATERIALS AND METHODS: For this purpose, 3 groups of
      virgin femal rats with 7,12 dimethylbenzanthracene-induced mammary cancer were
      treated using epigallocatechin-3-gallate, paclitaxel or their combination.
      RESULTS: It was found that epigallocatechin-3-gallate exhibited significant
      chemopreventive effects and anti-cancer stem cell activity through several
      pathways, including a significant decrease in the size and number of tumors per
      rat, significant amelioration of the oxidative stress markers' alterations and
      significant inhibition of CD44, VEGF, Ki-67 and MMP-2 expression associated with
      a significantly increased expression of caspase-3. Histopathologically, therapy
      with epigallocatechin-3-gallate resulted in marked necrosis of the neoplastic
      cells and the tumor masses were mostly replaced by proliferated fibrous tissue so
      that histological confirmation of a previous tumor was not possible at that site.
      However, in the combination therapy the neoplastic cells showed marked
      vacuolation, haphazard arrangement and extensive nuclear pyknosis accompanied
      with many apoptotic bodies. Therapy with the sole paclitaxel caused variable
      degrees of necrosis among the neoplastic cells. Additionally, the combination of
      epigallocatechin-3-gallate and paclitaxel significantly enhanced the later
      anticancer efficacy. CONCLUSIONS: Epigallocatechin-3-gallatecould be offered as
      an unprecedented curative strategy to eradicate cancer.

PMID- 28755735
TI  - Pancreatic Head Actinomycosis.

PMID- 28755736
TI  - Multiple Endocrine and Neoplastic Diseases After Unsuccessful Treatment of
      Hepatitis C With Interferon and Ribavirin.

PMID- 28755737
TI  - Scimitar Syndrome With an Absent Right Upper Lung Lobe.

PMID- 28755738
TI  - Plasmodium falciparum Exflagellation in a Patient With Ovalocytosis.

PMID- 28755739
TI  - Triple Threat in Infective Endocarditis: A Fatal Combo.

PMID- 28755740
TI  - Vascular Damage and Kidney Transplant Outcomes: An Unfriendly and Harmful Link.
AB  - Kidney transplant (KT) is the treatment of choice for most patients with chronic
      kidney disease, but this has a high cardiovascular mortality due to traditional
      and nontraditional risk factors, including vascular calcification. Inflammation
      could precede the appearance of artery wall lesions, leading to arteriosclerosis
      and clinical and subclinical atherosclerosis in these patients. Additionally,
      mineral metabolism disorders and activation of the renin-angiotensin system could
      contribute to this vascular damage. Thus, understanding the vascular lesions that
      occur in KT recipients and the pathogenic mechanisms involved in their
      development could be crucial to optimize the therapeutic management and outcomes
      in survival of this population. This review focuses on the following issues: (1)
      epidemiological data framing the problem; (2) atheromatosis in KT patients:
      subclinical and clinical atheromatosis, involving ischemic heart disease,
      congestive heart failure, stroke and peripheral vascular disease; (3)
      arteriosclerosis and vascular calcifications; and (4) potential pathogenic
      mechanisms and their therapeutic targets.

PMID- 28755741
TI  - Gastric Kaposi's Sarcoma.

PMID- 28755742
TI  - A Canine Kidney Conundrum.

PMID- 28755743
TI  - Presentation of 2017 SSCI Founders' Medal.

PMID- 28755744
TI  - 2017 Founders' Medal Acceptance.

PMID- 28755745
TI  - [Potassium, the narrow strip between life and death].

PMID- 28755746
TI  - Genome-wide profiling of differentially spliced mRNAs in human fetal cortical
      tissue exposed to alcohol.
AB  - Excessive alcohol consumption results in significant changes in gene expression
      and isoforms due to altered mRNA splicing. As such, an intriguing possibility is
      that disturbances in alternative splicing are involved in key pathological
      pathways triggered by alcohol exposure. However, no resources have been available
      to systematically analyze this possibility at a genome-wide scale. Here, we
      performed RNA sequencing of human fetal cortical slices that were obtained at the
      late first trimester and exposed to ethanol or control medium. We report 382
      events that were identified as changes affecting the ratio of splicing isoforms
      in the ethanol-exposed fetal human cortex. Additionally, previously unreported
      novel isoforms of several genes were also identified. These results provide a
      broad perspective on the post-transcriptional regulatory network underlying
      ethanol-induced pathogenesis in the developing human cortex.

PMID- 28755747
TI  - A prospective cohort study examining the effectiveness of baclofen in the
      maintenance of abstinence in alcohol use disorder patients attending a joint
      liver and alcohol treatment clinic.
AB  - OBJECTIVE: Alcohol-related liver disease (ARLD) is the leading cause of alcohol
      related mortality in the UK. Helping patients with ARLD to stop drinking is an
      important treatment goal. The aim of this study is to explore baclofen's utility
      in maintaining abstinence. METHODS - A PROSPECTIVE COHORT STUDY: Patients with
      ARLD were commenced on baclofen; the dose was titrated according to tolerability
      and response up to 30 mg three times daily. Severity of physical dependence and
      biochemical markers of liver injury were assessed at baseline, 3 months, and 12
      months. RESULTS: Length of follow-up differed. Of 219 patients in the original
      cohort, 186 and 113 were evaluated at 3 months and 12 months, respectively. Loss
      to follow-up was due to death, baclofen non-adherence, and failure to attend
      appointments. Comparison of baseline and 1-year biochemical markers showed
      significant reductions in GGT (median change = 82.0; 95% CI = -149.0 to -40.0; p
      < 0.0005), ALT (-10.5; 95% CI = -16.5 to -5.0; p = 0.001), and bilirubin (-4.5;
      95% CI = -7.0 to -2.0; p < 0.001). The proportion of eligible patients reporting
      complete abstinence at 3 and 12 months was 55% and 53%, respectively. A
      significant reduction in alcohol consumption and Severity of Alcohol Dependence
      Questionnaire score was observed at both follow-up time points. CONCLUSION:
      Adherence to the baclofen was good, and it had a positive impact on measures of
      alcohol consumption. A limitation of our study is its observational nature.
      Further randomized studies alongside investigation of dosing strategies are
      required.

PMID- 28755748
TI  - A modified Timeline Followback assessment to capture alcohol exposure in pregnant
      women: Application in the Safe Passage Study.
AB  - Prenatal alcohol exposure (PAE) has been linked to poor pregnancy outcomes, yet
      there is no recognized standard for PAE assessment, and the specific effects of
      quantity, frequency, and timing remain largely unknown. The Safe Passage Study
      was designed to investigate the role of PAE in a continuum of poor peri- and
      postnatal outcomes. The objective of this manuscript is to describe the rationale
      for, and feasibility of, modifications to the traditional Timeline Followback
      (TLFB) for collecting PAE information in a large cohort of pregnant women.
      Participants from the Northern Plains region (in the United States) and Cape
      Town, South Africa, were followed prospectively using a modified 30-day TLFB
      interview, administered up to five times, to obtain detailed PAE information.
      Required modifications for our population included capturing information
      regarding sharing, type/brand, container size, and duration, in order to
      accurately record the amount of alcohol consumed. PAE status was defined for
      99.9% of the 11,892 enrolled pregnancies at least once during pregnancy and for
      92% across all trimesters. Of 53,823 drinks reported, 98% had all items necessary
      for standard drink computation. Sharing was reported for 74% of drinks in Cape
      Town, South Africa and for 10% in the Northern Plains. Compared to referent
      values from the traditional TLFB, 74% and 67% of drinks had different alcohol-by
      volume and container size, respectively. Furthermore, a statistically significant
      difference was found between the number of containers reported and the number of
      standard drinks computed, using information from the modified TLFB. This is the
      first study of this size to wholly encompass all of these changes into a single
      measure in order to more accurately calculate daily consumption and assess
      patterns over time. The methods used to collect PAE information and create
      alcohol exposure measures likely increased the accuracy of standard drinks
      reported and could be generalized to other populations.

PMID- 28755749
TI  - Increased expression of M1 and M2 phenotypic markers in isolated microglia after
      four-day binge alcohol exposure in male rats.
AB  - Microglia activation and neuroinflammation are common features of
      neurodegenerative conditions, including alcohol use disorders (AUDs). When
      activated, microglia span a continuum of diverse phenotypes ranging from
      classically activated, pro-inflammatory (M1) microglia/macrophages to
      alternatively activated, growth-promoting (M2) microglia/macrophages. Identifying
      microglia phenotypes is critical for understanding the role of microglia in the
      pathogenesis of AUDs. Therefore, male rats were gavaged with 25% (w/v) ethanol or
      isocaloric control diet every 8 h for 4 days and sacrificed at 0, 2, 4, and 7
      days after alcohol exposure (e.g., T0, T2, etc.). Microglia were isolated from
      hippocampus and entorhinal cortices by Percoll density gradient centrifugation.
      Cells were labeled with microglia surface antigens and analyzed by flow
      cytometry. Consistent with prior studies, isolated cells yielded a highly
      enriched population of brain macrophages/microglia (>95% pure), evidenced by
      staining for the macrophage/microglia antigen CD11b. Polarization states of
      CD11b+CD45low microglia were evaluated by expression of M1 surface markers, major
      histocompatibility complex (MHC) II, CD32, CD86, and M2 surface marker, CD206
      (mannose receptor). Ethanol-treated animals begin to show increased expression of
      M1 and M2 markers at T0 (p = n.s.), with significant changes at the T2 time
      point. At T2, expression of M1 markers, MHC-II, CD86, and CD32 were increased (p
      < 0.05) in hippocampus and entorhinal cortices, while M2 marker, CD206, was
      increased significantly only in entorhinal cortices (p < 0.05). All effects
      resolved to control levels by T4. In summary, four-day binge alcohol exposure
      produces a transient increase in both M1 (MHC-II, CD32, and CD86) and M2 (CD206)
      populations of microglia isolated from the entorhinal cortex and hippocampus.
      Thus, these findings that both pro-inflammatory and potentially beneficial,
      recovery-promoting microglia phenotypes can be observed after a damaging exposure
      of alcohol are critically important to our understanding of the role of microglia
      in the pathogenesis of AUDs.

PMID- 28755750
TI  - Efficient determination of six fatty acid ethyl ethers in human whole blood by
      gas chromatography-mass spectrometry.
AB  - Fatty acid ethyl esters (FAEEs) have been widely studied as specific markers of
      ethanol intake and mediators of ethanol-induced diseases. In the present study, a
      simple and rapid gas chromatography-mass spectrometry (GC-MS) method was
      established for the qualitative and quantitative analysis of six fatty acid ethyl
      esters (FAEEs), including ethyl myristate, ethyl palmitate, ethyl stearate, ethyl
      oleate, ethyl linoleate, and ethyl arachidonate, in human whole blood. FAEEs were
      extracted from 200 MUL of human whole blood by a modified liquid-liquid
      extraction, and the hexane layer was injected directly into GC-MS with ethyl
      heptadecanoate as the internal standard. The limits of detection (LODs) and
      limits of quantification (LOQs) were in the range of 5-50 ng/mL and 15-200 ng/mL,
      respectively. Linearity ranged up to 10 MUg/mL with r2 higher than 0.998.
      Accuracy was in the range of 90.3-109.7%, while intra-day and inter-day precision
      were 0.7-9.3% and 3.4-12.5%, respectively. This method was then applied to 38
      real samples from forensic cases. Differences in the most common FAEEs between
      Chinese and Western subjects were discussed. The relationship of FAEE
      concentrations with age and gender was also investigated.

PMID- 28755754
TI  - Practice ownership is declining.

PMID- 28755755
TI  - Tension and Elasticity Contribute to Fibroblast Cell Shape in Three Dimensions.
AB  - The shape of animal cells is an important regulator for many essential processes
      such as cell migration or division. It is strongly determined by the organization
      of the actin cytoskeleton, which is also the main regulator of cell forces.
      Quantitative analysis of cell shape helps to reveal the physical processes
      underlying cell shape and forces, but it is notoriously difficult to conduct it
      in three dimensions. Here we use direct laser writing to create 3D open scaffolds
      for adhesion of connective tissue cells through well-defined adhesion platforms.
      Due to actomyosin contractility in the cell contour, characteristic invaginations
      lined by actin bundles form between adjacent adhesion sites. Using quantitative
      image processing and mathematical modeling, we demonstrate that the resulting
      shapes are determined not only by contractility, but also by elastic stress in
      the peripheral actin bundles. In this way, cells can generate higher forces than
      through contractility alone.

PMID- 28755751
TI  - Drinking and smoking patterns during pregnancy: Development of group-based
      trajectories in the Safe Passage Study.
AB  - Precise identification of drinking and smoking patterns during pregnancy is
      crucial to better understand the risk to the fetus. The purpose of this
      manuscript is to describe the methodological approach used to define prenatal
      drinking and smoking trajectories from a large prospective pregnancy cohort, and
      to describe maternal characteristics associated with different exposure patterns.
      In the Safe Passage Study, detailed information regarding quantity, frequency,
      and timing of exposure was self-reported up to four times during pregnancy and at
      1 month post-delivery. Exposure trajectories were developed using data from
      11,692 pregnancies (9912 women) where pregnancy outcome was known. Women were
      from three diverse populations: white (23%) and American Indian (17%) in the
      Northern Plains, US, and mixed ancestry (59%) in South Africa (other/not
      specified [1%]). Group-based trajectory modeling was used to identify 5 unique
      drinking trajectories (1 none/minimal, 2 quitting groups, 2 continuous groups)
      and 7 smoking trajectories (1 none/minimal, 2 quitting groups, 4 continuous
      groups). Women with pregnancies assigned to the low- or high-continuous drinking
      groups were less likely to have completed high school and were more likely to
      have enrolled in the study in the third trimester, be of mixed ancestry, or be
      depressed than those assigned to the none/minimal or quit-drinking groups.
      Results were similar when comparing continuous smokers to none/minimal and quit
      smoking groups. Further, women classified as high- or low-continuous drinkers
      were more likely to smoke at moderate-, high-, and very high-continuous levels,
      as compared to women classified as non-drinkers and quitters. This is the first
      study of this size to utilize group-based trajectory modeling to identify unique
      prenatal drinking and smoking trajectories. These trajectories will be used in
      future analyses to determine which specific exposure patterns subsequently
      manifest as poor peri- and postnatal outcomes.

PMID- 28755756
TI  - Brain Extracellular Space: The Final Frontier of Neuroscience.
AB  - Brain extracellular space is the narrow microenvironment that surrounds every
      cell of the central nervous system. It contains a solution that closely resembles
      cerebrospinal fluid with the addition of extracellular matrix molecules. The
      space provides a reservoir for ions essential to the electrical activity of
      neurons and forms an intercellular chemical communication channel. Attempts to
      reveal the size and structure of the extracellular space using electron
      microscopy have had limited success; however, a biophysical approach based on
      diffusion of selected probe molecules has proved useful. A point-source paradigm,
      realized in the real-time iontophoresis method using tetramethylammonium, as well
      as earlier radiotracer methods, have shown that the extracellular space occupies
      ~20% of brain tissue and small molecules have an effective diffusion coefficient
      that is two-fifths that in a free solution. Monte Carlo modeling indicates that
      geometrical constraints, including dead-space microdomains, contribute to the
      hindrance to diffusion. Imaging the spread of macromolecules shows them
      increasingly hindered as a function of size and suggests that the gaps between
      cells are predominantly ~40 nm with wider local expansions that may represent
      dead-spaces. Diffusion measurements also characterize interactions of ions and
      proteins with the chondroitin and heparan sulfate components of the extracellular
      matrix; however, the many roles of the matrix are only starting to become
      apparent. The existence and magnitude of bulk flow and the so-called glymphatic
      system are topics of current interest and controversy. The extracellular space is
      an exciting area for research that will be propelled by emerging technologies.

PMID- 28755757
TI  - Understanding eating disorders within internalizing psychopathology: A novel
      transdiagnostic, hierarchical-dimensional model.
AB  - BACKGROUND: Several problems with the classification and diagnosis of eating
      disorders (EDs) have been identified, including proliferation of 'other
      specified' diagnoses, within-disorder heterogeneity, and frequent diagnostic
      migration over time. Beyond problems within EDs, past research suggested that EDs
      fit better in a spectrum of internalizing psychopathology (characterized by mood
      and anxiety disorders) than in a separate diagnostic class. PURPOSE: To develop a
      transdiagnostic, hierarchical-dimensional model relevant to ED psychopathology
      that: 1) reduces diagnostic heterogeneity, 2) includes important dimensions of
      internalizing psychopathology that are often excluded from ED diagnostic models,
      and 3) predicts clinical impairment. PROCEDURES: Goldberg's (2006) method and
      exploratory structural equation modeling were used to identify a hierarchical
      model of internalizing in community-recruited adults with EDs (N=207). FINDINGS:
      The lowest level of the hierarchy was characterized by 15 factors that defined
      specific aspects of eating, mood, and anxiety disorders. At the two-factor level,
      Internalizing bifurcated into Distress (low well-being, body dissatisfaction,
      suicidality, dysphoria, ill temper, traumatic intrusions) and Fear-Avoidance
      (claustrophobia, social avoidance, panic symptoms, dietary restricting, excessive
      exercise, and compulsions). Results showed that the lowest level of the hierarchy
      predicted 67.7% of the variance in clinical impairment. In contrast, DSM eating,
      mood, and anxiety disorders combined predicted 10.6% of the variance in
      impairment secondary to an ED. CONCLUSIONS: The current classification model
      represents an improvement over traditional nosologies for predicting clinically
      relevant outcomes for EDs.

PMID- 28755758
TI  - Reply.

PMID- 28755759
TI  - Reply.

PMID- 28755760
TI  - Association Between Nocturnal Blood Pressure Dips and Optic Disc Hemorrhage in
      Patients With Normal-Tension Glaucoma.

PMID- 28755761
TI  - Do quaternary ammonium monomers induce drug resistance in cariogenic, endodontic
      and periodontal bacterial species?
AB  - OBJECTIVES: Antibacterial monomers were developed to combat oral biofilm acids
      and caries; however, little is known on whether quaternary ammonium monomers
      (QAMs) would induce drug resistance in oral bacteria. The objective of this study
      was to investigate the effects of new antimicrobial monomers
      dimethylaminohexadecyl methacrylate (DMAHDM) and dimethylaminododecyl
      methacrylate (DMADDM) on the induction of drug resistance in eight species of
      cariogenic, endodontic and periodontal bacteria for the first time. METHODS:
      Streptococcus mutans (S. mutans), Streptococcus sanguis, Streptococcus gordonii,
      Enterococcus faecalis (E. faecalis), Aggregatibacter actinomycetemcomitans (A.
      actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum), Porphyromonas
      gingivalis (P. gingivalis), and Prevotella intermedia (P. intermedia) were
      tested. Minimum inhibitory concentration (MIC) was assessed using chlorhexidine
      (CHX) as control. Minimal bactericidal concentration (MBC), bacterial growth and
      membrane permeability properties were also investigated. RESULTS: CHX induced
      drug resistance in four species. DMAHDM did not induce any resistance. DMADDM
      induced drug resistance in only one benign species S. gordonii. The DMADDM
      resistant and CHX-resistant S. gordonii had the same MIC and MBC values as S.
      gordonii parental strain against DMAHDM (p>0.1), hence DMAHDM effectively
      inhibited the resistant strains. The resistant strains had slower growth
      metabolism than parental strain. SIGNIFICANCE: DMAHDM induced no drug resistance,
      and DMADDM had much less drug resistance than the commonly-used CHX in the eight
      common oral species. With its potent antimicrobial functions shown previously,
      the new DMAHDM is promising for applications in restorative, preventive,
      periodontal and endodontic treatments to combat cariogenic and pathological
      bacteria with no drug resistance in all tested species.

PMID- 28755762
TI  - Clinical Skills Performed By Iranian Emergency Nurses: Perceived Competency
      Levels and Attitudes Toward Expanding Professional Roles.
AB  - INTRODUCTION: Emergency nurses play an important role in the care of critically
      ill and injured patients, and their competency to perform clinical skills is
      vital to safe and effective patient care. The aim of this study was to evaluate
      the frequency of clinical skills performed and perceived competency levels among
      Iranian emergency nurses. In addition, attitudes toward expanding the
      professional roles of Iranian emergency nurses were also assessed. METHODS: In
      this descriptive correlational study, 319 emergency nurses from 30 hospitals in
      northwest Iran participated. Data were collected using a self-report
      questionnaire. Descriptive statistics and Pearson's correlation coefficient were
      used to present the findings. RESULTS: Overall competency of the emergency nurses
      was 73.31 +/- 14.2, indicating a good level of perceived competence. The clinical
      skills most frequently performed were in the domains of organizational and
      workload competencies (3.43 +/- 0.76), diagnostic function (3.25 +/- 0.82), and
      the helping role (3.17 +/- 0.83). A higher level of perceived competence was
      found for skills within these domains. Less frequently, participants performed
      skills within the domains of effective management of rapidly changing situations
      (2.70 +/- 0.94) and administering and monitoring therapeutic interventions (2.60
      +/- 0.97); a lower perceived level of competence was noted for these clinical
      skills. There was a significant correlation between frequency of performing
      clinical skills and perceived competency level (r = 0.651, P < .001).
      Participants had positive attitudes toward expanding their professional roles
      (2.13 +/- 0.92), with 81.5% agreeing it would improve their job satisfaction.
      DISCUSSION: Higher perceived competency levels were significantly associated with
      more frequent performance of clinical skills. This has implications for nurse
      managers and educators who may consider offering more frequent experiential and
      educational opportunities to emergency nurses. Expansion of nurses' roles could
      also result in increased experience in clinical skills and higher levels of
      competency. Research is needed to investigate nurses' clinical competence using
      direct and observed measures.

PMID- 28755764
TI  - A response to the commentary by Storch and Kay: Gaps in knowledge on the
      treatment of cannabis users with OCD.

PMID- 28755763
TI  - Reliability of Triage Nurses and Emergency Physicians for the Interpretation of
      the C-3PO Rule for Head Trauma in Children.
AB  - INTRODUCTION: The C-3PO rule has been validated for use by emergency physicians
      to identify young children at risk of skull fracture following head trauma. The
      use of the rule by triage nurses could improve patient flow in the emergency
      department. OBJECTIVES: To evaluate the interobserver agreement of triage nurses
      and emergency physicians in the interpretation of the C-3PO rule in a pediatric
      emergency department. METHODS: This was a prospective observational study
      performed in a consecutive sample of children visiting a single emergency
      department. Participants were all children younger than 24 months of age who
      presented at the emergency department for head trauma that had occurred in the
      previous 24 hours. The primary outcome was the interobserver agreement between
      nurses and emergency physicians as to whether the child was at high risk of skull
      fracture according to the interpretation of the C-3PO rule. All study
      participants were evaluated sequentially by a triage nurse and an emergency
      physician. Outcome of evaluation was kept blinded between nurses and physicians.
      The primary analysis was the interrater reliability using the kappa score. The
      sample size was set to provide lower boundary of 0.70 for a 95% confidence
      interval (95% CI) for kappa coefficient of at least 0.80. RESULTS: A total of 226
      children were evaluated by a physician and a nurse. Among them, 10 had skull
      fractures. A total of 34 nurses and 42 physicians evaluated between 1 and 21
      children. The interrater reliability was excellent, as demonstrated by a kappa
      score of 0.85 (95% CI: 0.77-0.92). Moreover, all children with skull fractures
      were categorized at "high risk" by the nurse and the physician. CONCLUSION: This
      study demonstrates an almost perfect interrater reliability between triage nurses
      and emergency physicians in interpreting the C-3PO rule when evaluating children
      who presented at an emergency department for head trauma. Contribution to
      Emergency Nursing Practice.

PMID- 28755766
TI  - Commentary on Spradlin et al.: Is marijuana use common in OCD?

PMID- 28755765
TI  - Cultural values associated with substance use among Hispanic emerging adults in
      Southern California.
AB  - INTRODUCTION: Hispanic emerging adults are a priority population for substance
      use prevention, yet few studies have examined whether traditional Hispanic
      cultural values serve as risk or protective factors for substance use among
      emerging adults. This study examined the relationship between familism, respeto,
      fatalism, and substance use among Hispanic emerging adults. METHODS: Participants
      (ages 18 to 25) completed surveys indicating identification with familism,
      respeto, and fatalism, past month use of tobacco, marijuana, hard drugs and binge
      drinking. Separate logistic regression models examined the association between
      cultural values and each substance use outcome, controlling for acculturation,
      age and gender. RESULTS: Among participants (n=1445, mean age=23, 60% female),
      21% reported past month cigarette use, 18% reported past month alternative
      tobacco product (ATP) use, 25% reported past month marijuana use, 44% reported
      past month binge drinking, and 7% reported past month hard drug use. Higher
      fatalism scores were associated with increased ATP use. Higher familism scores
      were associated with binge drinking, while higher respeto scores were associated
      with decreased binge drinking, marijuana, and hard drug use. CONCLUSION: These
      findings suggest that substance use prevention and intervention programs should
      emphasize how substance use interferes with caring and honoring parents (respeto)
      and family cohesion and functioning (familism). Programs that highlight these
      cultural values and beliefs may be beneficial for Hispanic emerging adults and
      members of other collectivistic cultures.

PMID- 28755767
TI  - Hypoglossal nerve stimulation surgery for obstructive sleep apnoea: Our
      preliminary experience.
AB  - The objective of this communication is to describe our preliminary results in
      upper airway stimulation surgery via hypoglossal nerve stimulation implantation
      for obstructive sleep apnoea. We describe 4 cases and the outcomes of the surgery
      were analysed using the Epworth scale, apnoea-hypopnoea index, minimal O2 Sat,
      average O2 Sat and snoring intensity. In all cases a significant reduction in
      Epworth scale values and apnoea-hypopnoea index were obtained (P<.05). The
      minimum and average oxygen saturation had better values after the surgery,
      however, there was no statistically significant difference. The snoring severity
      measured subjectively changed from "intense" to "absent" in all cases. The
      preliminary results obtained with the upper airway stimulation surgery via
      hypoglossal nerve stimulation showed objective and subjective improvement after
      the implant activation.

PMID- 28755768
TI  - A naturalistic study of predictors of retention in treatment among emerging
      adults entering first buprenorphine maintenance treatment for opioid use
      disorders.
AB  - INTRODUCTION: Emerging adulthood (between the ages 18-25years) has been
      conceptualized as a specific developmental stage based on unique psychosocial
      characteristics. Opioids are commonly used drugs in this population. Few studies
      have reported predictors of retention in buprenorphine maintenance treatment
      among opioid-dependent emerging adults, particularly from India. Moreover, no
      study has examined outcomes with opioid maintenance treatment among emerging
      adults in non-clinical trial, naturalistic settings. The current study aimed to
      assess retention in buprenorphine maintenance treatment among emerging adults in
      a naturalistic setting. Also, it aimed to assess the factors associated with
      retention in treatment among these individuals. METHODS: The current study was a
      retrospective cohort study conducted at a substance use disorder treatment centre
      in northern part of India. The patients who received buprenorphine maintenance
      treatment between 1st January 2012 and 31st December 2014 were eligible for
      inclusion in the current study. The follow-up data of these subjects were
      assessed up to and including 31st March 2015. Information was retrieved on socio
      demographic variables. The information related to substance use included type of
      substance, duration of use, age of onset, motive of use, route of administration
      and source of procurement. Additionally, details of buprenorphine dose,
      dispensing pattern, induction settings were recorded. Cox regression analysis was
      carried out to assess the predictors of retention in buprenorphine maintenance
      treatment. RESULTS: Of 68 emerging adults, 33.8% were retained in treatment at
      90days, 19.1% at 6months and 11.7% at one year. After controlling for various
      covariates in adjusted Cox regression analysis, substance use in first degree
      relatives (AHR: 2.40, 95% CI 1.33-4.31), lower daily buprenorphine dose (AHR:
      0.86, 95% CI 0.78-0.94) and past month injection drug use (AHR: 0.30, 95% CI 0.14
      0.66) were found to be the significant predictors of treatment dropout.
      CONCLUSIONS: The findings of the current study help understand the predictors of
      retention in buprenorphine maintenance treatment among emerging adults in a real
      world situation. These findings will help guide formulation of responsive and
      relevant buprenorphine maintenance treatment program for the emerging adults.

PMID- 28755769
TI  - Alcohol and cocaine use among Latino and African American MSM in 6 US cities.

PMID- 28755770
TI  - Association of methadone dose with substance use and treatment retention in
      pregnant and postpartum women with opioid use disorder.
AB  - BACKGROUND: In non-pregnant individuals being treated for opioid use disorder
      (OUD) with methadone, doses >=60mg per day are associated with improved treatment
      retention and decreased illicit opioid use. Although methadone remains the first
      line treatment for OUD in pregnant women, there are no studies replicating this
      finding in pregnancy. METHODS: We conducted a retrospective cohort study of 189
      pregnant women treated with methadone for OUD from 2006 to 2013. Chart data
      collected included demographics, pregnancy dates, methadone doses, and urine drug
      screen (UDS) results. RESULTS: Treatment retention at delivery was significantly
      higher for subjects taking >=60mg of methadone (90.1% v. 74.1% p<0.005), as was
      treatment retention at 60days postpartum (71.6% v. 37.0%, p<0.0001). Percent of
      UDS results negative for illicit substances during pregnancy was also
      significantly higher for subjects taking >=60mg (71.5% v. 58.0%, p<0.04). There
      was no significant difference in UDS results in the first 60days postpartum
      (63.9% v. 68.1%). Generalized linear models showed a significant positive
      relationship between methadone dose and treatment retention at delivery (p<0.02)
      and at 60days postpartum (p<0.004) as well as a significant positive relationship
      between length of time in treatment and treatment retention at delivery (p<0.04)
      and at 60days postpartum (p<0.007). Maternal age and percent of negative UDS
      results were not predictive of treatment retention in either model and there was
      no significant interaction effect between methadone dose and percent negative UDS
      results. CONCLUSIONS: In this cohort, women taking >=60mg of methadone during
      pregnancy were more likely to remain in treatment and to provide urine samples
      negative for illicit drugs. Multivariate modeling suggested a dose dependent
      response across the entire dose range, rather than a threshold effect at 60mg.

PMID- 28755771
TI  - Cessation support for smokers with mental health problems: a survey of resources
      and training needs.
AB  - AIMS: Around thirty percent of smokers have a mental health problem. Smoking
      cessation has been associated with mental health benefits, but smoking prevalence
      remains high in populations with mental health problems. This study aimed to
      assess mental health related knowledge, practice, and training needs of
      practitioners supporting smoking cessation. METHODS: UK stop smoking
      practitioners (n=717) recruited via a database of a national provider of smoking
      cessation training in June 2016 sufficiently completed an online survey about
      available resources, knowledge, confidence, and training needs related to smoking
      cessation and mental health. Responses were described and compared between
      practitioners with a mental health lead and those without such a lead in their
      service using chi-square statistics and t-tests. RESULTS: A considerable
      proportion agreed (37%) or were undecided (28.9%) that smoking helped people with
      mental health problems feel better and agreed (17.2%) or were undecided (30.2%)
      that cessation would exacerbate mental health symptoms. Only 11.6% said their
      service had designated funding for smokers with mental health problems and 26.5%
      were or had a staff member who was a dedicated lead practitioner for mental
      health work. Practitioners from services that had a dedicated mental health lead
      were more confident in supporting smokers with different mental health problems
      and using different pharmacotherapies (all p<0.001) and were more likely to
      disagree that cessation was detrimental (p=0.001). A majority of practitioners
      were interested in training, particularly about smoking cessation effects on
      psychiatric medication (84.3% of n=632) and how to tailor stop smoking support to
      clients with mental health problems (82.4%). CONCLUSION: Practitioners who
      support smoking cessation have limited knowledge about mental health and smoking
      but are willing to learn and improve. However, they are hindered by a lack of
      resources.

PMID- 28755772
TI  - Demographic and clinical characteristics of treatment seeking women with full and
      subthreshold PTSD and concurrent cannabis and cocaine use disorders.
AB  - While the detrimental effects of concurrent substance use disorders (SUDs) are
      now being well documented, very few studies have examined this comorbidity among
      women with posttraumatic stress disorder (PTSD). Data for these analyses were
      derived from the "Women and Trauma" study conducted within the National Drug
      Abuse Treatment Clinical Trials Network. Women with full or subthreshold PTSD and
      co-occurring cannabis use disorder (CUD) and cocaine use disorder (COD; N=99)
      were compared to their counterparts with co-occurring CUD only (N=26) and co
      occurring COD only (N=161) on rates of trauma exposure, psychiatric disorders,
      psychosocial problems, and other substance use utilizing a set of multivariate
      logistic regressions. In models adjusted for age and race/ethnicity, women with
      PTSD and COD only were significantly older than their counterparts with CUD only
      and concurrent CUD+COD. Relative to those with CUD only, women with concurrent
      CUD+COD had higher odds of adult sexual assault. Relative to those with COD only,
      women with concurrent CUD+COD had higher odds of alcohol use disorder in the past
      12months. Finally, relative to those with CUD only, women with COD only had
      higher odds of ever being arrested/convicted and adult sexual assault. The higher
      rates of adult sexual assault and alcohol use disorder among those with
      concurrent CUD+COD suggest the need for trauma-informed approaches that can
      respond to the needs of this dually-diagnosed population. Moreover, the causal
      link between repeated traumatic stress exposure and polysubstance use requires
      further examination.

PMID- 28755773
TI  - Patient adherence to multi-component continuing care discharge plans.
AB  - Intuitively, it is assumed that greater patient adherence to treatment
      recommendations in substance use disorder (SUD) treatment is associated with
      favorable outcomes, but surprisingly, there is limited research systematically
      examining the adherence-outcome relationship in the context of the continuing
      care phase post-discharge from residential treatment. This study sought to
      determine the effect of adherence to multi-component continuing care plans on
      long-term outcomes among patients following the primary treatment episode. Data
      were abstracted from electronic medical records for 271 patients (59.0% male)
      discharged from a U.S. residential program between 2013 and 2015. Patients were
      categorized based on their level of adherence to their individualized continuing
      care discharge plan, and studied through retrospective record review for 12months
      post-discharge. 12-month outcomes included past 30-day and continuous abstinence,
      re-admission, and quality of life. With the exception of re-admission rate, fully
      adherent patients demonstrated significantly better results on all study outcomes
      at 12months compared to patients who were partially or non-adherent. Fully
      adherent patients were 9.46 times (95% CI: 5.07-17.62) more likely to be
      continuously abstinent through 12months relative to the other adherence groups.
      Fully adherent patients were 7.53 times (95% CI: 2.41-23.50) more likely to
      report a positive quality of life at 12months relative to the other adherence
      groups. The findings support the widely held contention that greater adherence to
      continuing care discharge plans is associated with favorable long-term outcomes,
      and provide insight into realistic outcomes expectations for patients who are
      adherent to their multi-component continuing care discharge plans.

PMID- 28755774
TI  - Effectiveness of a computerized motivational intervention on treatment initiation
      and substance use: Results from a randomized trial.
AB  - As many as 80% of the nearly five million adults under community supervision
      (i.e., probation, parole) are substance involved; however, treatment utilization
      is low. Using a multi-site randomized controlled trial, we tested the efficacy of
      in-person motivational interviewing (MI), a motivational computer intervention
      (MAPIT), or standard probation intake (SAU) to encourage treatment initiation
      among 316 substance-involved probationers in Dallas, Texas and Baltimore City,
      Maryland. Ninety-three percent (n=295) of participants completed the 2-month
      follow-up and 90% (n=285) completed the 6-month follow-up. At 2-months,
      individuals in the MAPIT condition were more likely to report treatment
      initiation compared to the SAU condition (OR=2.40, 95% CI=1.06, 5.47) via intent
      to-treat analysis, especially among those completing both sessions (RE=0.50, 95%
      CI=0.05, 0.95) via instrumental variable analysis. At 6-months, MAPIT approached
      significance for treatment initiation in both analyses. MI did not achieve
      significance in any model. We did not find any differential impact on substance
      use. The success of MAPIT suggests that an integrated health-justice computerized
      intervention as part of a Screening, Brief Intervention, and Referral to
      Treatment (SBIRT) can be used to address public safety and health issues.

PMID- 28755775
TI  - A systematic review of the relationship between staff perceptions of
      organizational readiness to change and the process of innovation adoption in
      substance misuse treatment programs.
AB  - Translating innovation, such as contemporary research evidence, into policy and
      practice is a challenge, not just in substance misuse treatment programs, but
      across all spheres of healthcare. Organizational readiness to change (ORC) has
      been described as a fundamental concept, and an important determinant of the
      process of innovation adoption. The aim of this review was to describe the
      relationship between staff perceptions of ORC and the process of innovation
      adoption: exposure, adoption, implementation and integration into practice, in
      substance misuse treatment programs. This systematic review was conducted in
      accordance with PRISMA guidelines and fourteen papers were identified as being
      eligible for inclusion. This review was designed to include all constructs of
      ORC, but only one tool was used in all of the included papers. Despite this, the
      heterogeneity of studies in this review made a direct comparison of ORC related
      variables challenging. None of the included papers clearly related to one stage
      of the process of innovation adoption, and all of the included papers related to
      the early stages of the process. Only one paper attempted to measure the
      sustained integration of an innovation into practice. Overall, the papers were
      assessed as being low in terms of evidential hierarchy and the quality of the
      papers was assessed as being on average fair. ORC measurements provide us with a
      measure of organizational functioning which can be important in terms of
      predicting how successfully new innovations are adopted. Motivation for change
      was high in programs where staff identified more program deficits and these staff
      could also identify more specific needs, but were less likely to have exposure to
      new innovations. Better program resources and specific staff attributes, increase
      the likely hood of successful innovation adoption. A good organizational climate
      is potentially the strongest predictor for the adoption of new practices. It may
      be beneficial to measure ORC in conjunction with other variables such as program
      size, location, staff workloads and financial resources. More evidence is
      required on how to address ORC deficits once they are identified in practice.

PMID- 28755776
TI  - The Mental Health Parity and Addiction Equity Act evaluation study: Impact on
      specialty behavioral healthcare utilization and spending among enrollees with
      substance use disorders.
AB  - BACKGROUND: The federal Mental Health Parity and Addiction Equity Act (MHPAEA)
      sought to eliminate historical disparities between behavioral health and medical
      health insurance benefits among the commercially insured. This study determines
      whether MHPAEA was associated with increased BH expenditures and utilization
      among a population with substance use disorder (SUD) diagnoses. METHODS: Claims
      and eligibility data from 5,987,776 enrollees, 2008-2013, were obtained from a
      national, commercial, managed behavioral health organization. An interrupted time
      series study design with segmented regression analysis estimated time trends of
      per-member-per-month (PMPM) spending and use before (2008-2009), during (2010),
      and after (2011-2013) MHPAEA compliance. The study sample contained individuals
      with drug or alcohol use disorder diagnosis during study period (N=2,716,473
      member-month observations). Outcomes included: total, plan, patient out-of-pocket
      spending; outpatient utilization (assessment/diagnostic evaluation visits;
      medication management; individual, group and family psychotherapy, and structured
      outpatient care); intermediate care utilization (day treatment; recovery home and
      residential); and inpatient utilization. RESULTS: Starting at the beginning of
      the post-parity period, MHPAEA was associated with increased levels of PMPM total
      and plan spending ($25.80 [p=0.01]; $28.33 [p=0.00], respectively), as well as
      the number of PMPM assessment/evaluation, individual psychotherapy, and group
      psychotherapy visits, and inpatient days (0.01 visits [p=0.01]; 0.02 visits
      [p=0.01]; 0.01 visits [p=0.03]; 0.01days [p=0.01], respectively). Following these
      initial level changes, MHPAEA was also associated with monthly increases in PMPM
      total, plan, and patent out-of-pocket spending ($2.56/month [p=0.00]; $2.25/month
      [p=0.00]; $0.27 [p=0.03], respectively), as well as structured outpatient visits
      and inpatient days (0.0012 visits/month [p=0.01]; 0.0012days/month [p=0.00]).
      CONCLUSION: MHPAEA was associated with modest increases in total, plan, and
      patient out-of-pocket spending and outpatient and inpatient utilization. These
      increases, while modest in magnitude, are larger in magnitude than increases
      detected among a sample of all enrollees (i.e. not only those with SUD
      diagnoses).

PMID- 28755777
TI  - Dispositional and situational coping among individuals with alcohol use disorder.
AB  - Previous research has documented that patients referred for problems related to
      alcohol use rely primary on maladaptive coping and are deficient in adaptive
      coping skills. However, the relation between dispositional and situational coping
      in these patients is not yet fully understood. Therefore, the first aim of the
      present study was to assess dispositional and situational coping among
      individuals with alcohol use disorder compared to matched healthy controls.
      Furthermore, we aimed at assessing gender differences in dispositional and
      situational coping among individuals with alcohol use disorder. Fifty-five
      patients with alcohol use disorder were compared to 55 age, years of education,
      and gender-matched healthy volunteers. Participants filled out the Coping
      Orientation to Problem Experiences-New Italian version assessing dispositional
      coping and the Coping Responses Inventory - Adult Form assessing situational
      coping. Regarding dispositional coping, patients with alcohol use disorder
      employed more avoidant coping styles compared to matched healthy controls. No
      differences between groups emerged on situational coping. With respect to gender
      differences in dispositional coping, women, regardless of group membership,
      employed more coping styles aimed at construing a stressful transaction in
      positive terms and turned to religion more relative to men. With respect to
      situational coping, women, again regardless of group membership, employed more
      strategies aimed at construing a stressful transaction in positive terms and more
      problem-solving strategies compared to men. Results of the present study may
      assist with treatment planning for alcohol use disorder and lead to the
      development of treatment programs targeting patients' specific coping
      difficulties.

PMID- 28755779
TI  - Thermo- and soluto-capillarity: Passive and active drops.
AB  - A survey is provided of a variety of problems where a passive or an active drop
      experiences directed motion consequence of the action of an external or internal
      agent or a combination of both. An active drop is capable of reacting by
      engendering autonomous, self-propelled motion in favor or against the agent. The
      phenomena involved offer diverse complexity but one way or another the drop
      motion finally rests on thermo- or soluto-capillarity hence on interfacial
      tension gradients. Accordingly, here a minimal mathematical framework underlying
      such drop motions is provided when direct external temperature or solute
      gradients, illumination, internal heat generation or surface chemical reaction
      are incorporated into the physico-chemical-hydrodynamics.

PMID- 28755778
TI  - Developing a Fitbit-supported lifestyle physical activity intervention for
      depressed alcohol dependent women.
AB  - PURPOSE: Women in alcohol treatment are more likely to relapse when in
      unpleasant, negative emotional states. Given the demonstrated benefits of
      exercise for decreasing depression, negative affect, and urges to drink, helping
      women engage in a lifestyle physical activity (LPA) intervention in early
      recovery may provide them a tool they can utilize "in the moment" in order to
      cope with negative emotional states and alcohol craving when relapse risk is
      highest. New digital fitness technologies (e.g., Fitbit activity monitor with web
      and mobile applications) may facilitate increases in physical activity (PA)
      through goal setting and self-monitoring. METHOD: We piloted a 12-week LPA+Fitbit
      intervention focused on strategically using bouts of PA to cope with affect and
      alcohol cravings to prevent relapse in 20 depressed women (mean age=39.5years) in
      alcohol treatment. RESULTS: Participants wore their Fitbit on 73% of days during
      the intervention period. An average of 9174 steps/day were taken on the days the
      Fitbit was worn. Participants completed 4.7 of the 6 scheduled phone PA
      counseling sessions (78%). Among women who completed the intervention (n=15), 44%
      remained abstinent throughout the entire course of treatment. On average, women
      were abstinent on 95% of days during the 12-week intervention. Participants
      reported an increase in using PA to cope with either negative affect or urges to
      drink from baseline to end of treatment (p<0.05). Further, participants reported
      high satisfaction with the LPA+Fitbit intervention and with the Fitbit tracker.
      CONCLUSIONS: Further research is needed to evaluate the LPA+Fitbit intervention
      in a more rigorous randomized controlled trial. If the LPA+Fitbit intervention
      proves to be helpful during early recovery, this simple, low-cost and easily
      transported intervention can provide a much-needed alternate coping strategy to
      help reduce relapse risk among women in alcohol treatment.

PMID- 28755780
TI  - Dissipative dynamics of fluid lipid membranes enriched in cholesterol.
AB  - Cholesterol is an intriguing component of fluid lipid membranes: It makes them
      stiffer but also more fluid. Despite the enormous biological significance of this
      complex dynamical behavior, which blends aspects of membrane elasticity with
      viscous friction, their mechanical bases remain however poorly understood. Here,
      we show that the incorporation of physiologically relevant contents of
      cholesterol in model fluid membranes produces a fourfold increase in the membrane
      bending modulus. However, the increase in the compression rigidity that we
      measure is only twofold; this indicates that cholesterol increases coupling
      between the two membrane leaflets. In addition, we show that although cholesterol
      makes each membrane leaflet more fluid, it increases the friction between the
      membrane leaflets. This dissipative dynamics causes opposite but advantageous
      effects over different membrane motions: It allows the membrane to rearrange
      quickly in the lateral dimension, and to simultaneously dissipate out-of-plane
      stresses through friction between the two membrane leaflets. Moreover, our
      results provide a clear correlation between coupling and friction of membrane
      leaflets. Furthermore, we show that these rigid membranes are optimal to resist
      slow deformations with minimum energy dissipation; their optimized stability
      might be exploited to design soft technological microsystems with an encoded
      mechanics, vesicles or capsules for instance, useful beyond classical
      applications as model biophysical systems.

PMID- 28755781
TI  - Bone-forming agents in non-responders to bisphosphonates.

PMID- 28755782
TI  - Romosozumab (sclerostin monoclonal antibody) versus teriparatide in
      postmenopausal women with osteoporosis transitioning from oral bisphosphonate
      therapy: a randomised, open-label, phase 3 trial.
AB  - BACKGROUND: Previous bisphosphonate treatment attenuates the bone-forming effect
      of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a
      sclerostin monoclonal antibody, versus teriparatide on bone mineral density (BMD)
      in women with postmenopausal osteoporosis transitioning from bisphosphonate
      therapy. METHODS: This randomised, phase 3, open-label, active-controlled study
      was done at 46 sites in North America, Latin America, and Europe. We enrolled
      women (aged >=55 to <=90 years) with postmenopausal osteoporosis who had taken an
      oral bisphosphonate for at least 3 years before screening and alendronate the
      year before screening; an areal BMD T score of -2.5 or lower at the total hip,
      femoral neck, or lumbar spine; and a history of fracture. Patients were randomly
      assigned (1:1) via an interactive voice response system to receive subcutaneous
      romosozumab (210 mg once monthly) or subcutaneous teriparatide (20 MUg once
      daily). The primary endpoint was percentage change from baseline in areal BMD by
      dual-energy x-ray absorptiometry at the total hip through month 12 (mean of
      months 6 and 12), which used a linear mixed effects model for repeated measures
      and represented the mean treatment effect at months 6 and 12. All randomised
      patients with a baseline measurement and at least one post-baseline measurement
      were included in the efficacy analysis. This trial is registered with
      ClinicalTrials.gov, number NCT01796301. FINDINGS: Between Jan 31, 2013, and April
      29, 2014, 436 patients were randomly assigned to romosozumab (n=218) or
      teriparatide (n=218). 206 patients in the romosozumab group and 209 in the
      teriparatide group were included in the primary efficacy analysis. Through 12
      months, the mean percentage change from baseline in total hip areal BMD was 2.6%
      (95% CI 2.2 to 3.0) in the romosozumab group and -0.6% (-1.0 to -0.2) in the
      teriparatide group; difference 3.2% (95% CI 2.7 to 3.8; p<0.0001). The frequency
      of adverse events was generally balanced between treatment groups. The most
      frequently reported adverse events were nasopharyngitis (28 [13%] of 218 in the
      romosozumab group vs 22 [10%] of 214 in the teriparatide group), hypercalcaemia
      (two [<1%] vs 22 [10%]), and arthralgia (22 [10%] vs 13 [6%]). Serious adverse
      events were reported in 17 (8%) patients on romosozumab and in 23 (11%) on
      teriparatide; none were judged treatment related. There were six (3%) patients in
      the romosozumab group compared with 12 (6%) in the teriparatide group with
      adverse events leading to investigational product withdrawal. INTERPRETATION:
      Transition to a bone-forming agent is common practice in patients treated with
      bisphosphonates, such as those who fracture while on therapy. In such patients,
      romosozumab led to gains in hip BMD that were not observed with teriparatide.
      These data could inform clinical decisions for patients at high risk of fracture.
      FUNDING: Amgen, Astellas, and UCB Pharma.

PMID- 28755783
TI  - Health risks from exposure to untreated wastewater used for irrigation in the
      Mezquital Valley, Mexico: A 25-year update.
AB  - Wastewater reuse for agriculture is common worldwide; wastewater treatment,
      however, is rare in many countries, leading to high potential for exposure to
      harmful pathogens. Mexico City, one of the largest producers of untreated
      wastewater for agricultural use worldwide, was the site of key epidemiologic
      studies conducted in the 1990s. We both reviewed the literature on and conducted
      a cross-sectional study of diarrheal risk and wastewater contamination to provide
      an updated assessment of health risks and to inform an upcoming update of the
      2006 WHO guidelines on wastewater reuse. We surveyed communities in the Mezquital
      Valley that use wastewater for irrigation and communities that use well water to
      compare the prevalence of self-reported diarrheal disease in children under five
      years old. Wastewater, well water, household environmental samples, and stool
      samples were collected and analyzed. Communities exposed to wastewater had a
      higher one-week prevalence of diarrhea (10%) compared to unexposed communities
      (5%). This association remained in an adjusted modified Poisson regression model
      (PR = 2.31, 95% CI 1.00, 5.31), but not when limited to households engaged in
      agriculture. Water quality indicators document differences between irrigation
      water from the two community groups. These results are in agreement with 25
      population studies identified by our review that were conducted since or not
      included in the 2006 WHO guidelines and show consistent negative impacts of
      wastewater exposure on health. While overall diarrheal prevalence has declined
      when compared to studies conducted over 25 years ago in the same region, the
      association of diarrheal disease and wastewater exposure has remained and
      possibly increased. With rising urbanization worldwide, attention to these risks
      and wastewater treatment is becoming increasingly important.

PMID- 28755785
TI  - Author Reply.

PMID- 28755784
TI  - Prevalence of clinic-defined food allergy in early adolescence: The SchoolNuts
      study.
AB  - BACKGROUND: Rising rates of food-induced anaphylaxis have recently been shown in
      the adolescent age group, following earlier descriptions of a rise in children
      younger than 5 years. However, few population-based studies have examined the
      prevalence of food allergy in adolescence using objective measures such as oral
      food challenge (OFC). OBJECTIVE: We sought to determine the prevalence of food
      allergy among a population-based sample of 10- to 14-year-old adolescents using
      clinical evaluation including OFC to confirm the diagnosis. METHODS: Schools were
      randomly selected from greater metropolitan Melbourne, Australia. Students aged
      10 to 14 years, and their parents, were asked to complete a questionnaire
      regarding the adolescent's food allergy or food-related reactions. Clinic
      evaluation, which consisted of skin prick tests and OFC where eligible, was
      undertaken if students were suspected to have current food allergy from parent
      response. Among 9816 students assessed, 5016 had complete parent response and
      clinic evaluation when eligible. An additional 4800 students had student
      questionnaires only. RESULTS: The prevalence of clinic-defined current food
      allergy based on history, sensitization data, and OFC results was 4.5% (95% CI,
      3.9-5.1), with the most common food triggers being peanut, 2.7% (95% CI, 2.3
      3.2), and tree nut, 2.3% (95% CI, 1.9-2.8). Among the additional group of 4800
      adolescents who had only self-reported food allergy status available, the
      prevalence of self-reported current food allergy was 5.5% (95% CI, 4.9-6.2), with
      peanut, 2.8% (95% CI, 2.3-3.3), and tree nut, 2.3% (95% CI, 1.9-2.8), the most
      common. CONCLUSIONS: Approximately 1 in 20 10- to 14-year-old school students in
      Melbourne has current food allergy. This high prevalence suggests that the
      previously reported rise in food-induced anaphylaxis in this age group may
      reflect an increasing prevalence of food allergy rather than simply increased
      reporting of anaphylaxis.

PMID- 28755786
TI  - Editorial Comment.

PMID- 28755787
TI  - A hidden treasure of the Lower Pleistocene at Olduvai Gorge, Tanzania: The Leakey
      HWK EE assemblage.
AB  - HWK EE is a little-known archaeological site from the top of Lower Bed II and the
      basal part of Middle Bed II, Olduvai Gorge, Tanzania. The site was originally
      excavated in the early 1970s by Mary Leakey, but the excavations and resulting
      lithic and fossil assemblages were never described. Here we report for the first
      time on the lithic and fossil assemblages that were recovered by Mary Leakey from
      the site. The lithic assemblage is one of the largest of any Oldowan site and is
      characterized by a core-and-flake technology with simple flaking techniques and
      minimal reduction of cores. Retouched flake frequencies and battered tools are
      higher than those reported for Olduvai Bed I and Lower Bed II assemblages, but
      flaking schemes are poorly organized. The fossil assemblage is well-preserved,
      taxonomically-rich, but dominated by bovids, and includes abundant feeding traces
      of both hominins and carnivores. Hominins are inferred to have broken the
      majority of limb bones at the site for access to marrow, while both carnivores
      and hominins likely had access to at least some flesh. HWK EE may represent one
      of the last Homo habilis sites at Olduvai Gorge, and is important to
      understanding the behavioral and cultural mechanisms that led to the emergence of
      the Acheulean and Homo erectus in the region.

PMID- 28755788
TI  - Concordance of autoimmune disease in a nationwide Danish systemic lupus
      erythematosus twin cohort.
AB  - OBJECTIVE: To determine the concordance of systemic lupus erythematosus (SLE) and
      co-aggregating autoimmune diseases among Danish twins. METHODS: SLE-affected
      twins were ascertained by record linkage between the National Patient Register
      (NPR) and the Danish Twin Registry (DTR). Registered SLE codes were validated
      through medical chart review and information from the treating physicians. Twin
      pairs with at least one chart-validated SLE proband were invited to participate
      in a personal interview and clinical validation of the SLE diagnoses. RESULTS:
      Twenty-two twins fulfilled the ACR criteria for SLE. The age- and sex-adjusted
      point SLE prevalence in the Danish twin cohort was 30.3 per 100,000 persons (95%
      CI: 19.2-46.5). Among seven monozygotic (MZ), eight same-sex dizygotic (DZss) and
      five opposite-sex dizygotic (DZos) twin pairs, one MZ and one DZss were
      concordant for SLE. This corresponded to probandwise concordance rates of 25.0%
      (95% CI: 7.15-59.1) and 7.7% (95% CI: 1.37-33.3), and pairwise concordance rates
      of 14.3% (95% CI: 2.57-51.3) and 7.7% (95% CI: 1.37-33.3) among MZ and DZ twins,
      respectively. An SLE diagnosis was clinically validated in 17 twins from 15 twin
      pairs. Another four co-twins had other autoimmune disease, corresponding to a
      probandwise concordance of any autoimmune disease of 50.0% in MZ (95% CI: 21.5
      78.5) and 23.1% in DZ twins (95% CI: 8.18-50.3). CONCLUSION: Population-based
      Danish data suggest that SLE twin concordance is lower than previously reported,
      but still point to the importance of both genetic and environmental factors, and
      indicate a substantial co-aggregation of other autoimmune diseases in SLE twins.

PMID- 28755789
TI  - Minimally Complex Renal Cysts: Outcomes and Ultrasound Evaluation Compared with
      Contrast-Enhanced Cross-Sectional Imaging Bosniak Classification.
AB  - We correlated contrast-enhanced cross-sectional imaging and outcomes to assess
      the reproducibility of ultrasonographic criteria for renal minimally complex (MC)
      cysts. From 2003 to 2015, 143 cysts were described as complex or MC by ultrasound
      (US). After exclusions, 98 US studies were retrospectively evaluated and compared
      with computed tomography (CT)/magnetic resonance imaging (MRI). At sonography, 51
      were MC cysts and 47 were complexes according to two independent observers. Inter
      observer agreement for US was 0.704 and 0.745 for CT/MRI. Of 51 cysts classified
      as MC by US, 38 were Bosniak I/II and 6 were Bosniak IIF by CT/MRI. In 7, there
      were no cross-sectional images; however, they were stable for at least 2 y. Of 47
      complex cysts, 9 were Bosniak II, 22 Bosniak IIF, 8 Bosniak III and 8 Bosniak IV.
      No Bosniak III/IV cysts by CT/MRI were classified as MC by US. Our results
      indicate that US offers reproducible criteria for MC cysts and may be used alone
      for these lesions.

PMID- 28755790
TI  - Correlation between Disease Activity and Endorectal Ultrasound Findings of
      Chronic Radiation Proctitis.
AB  - The aim of this study was to summarize the imaging features of chronic radiation
      proctitis (CRP) on endorectal ultrasound (ERUS) and investigate the value of ERUS
      in the evaluation of disease activity. 40 CRP patients and 30 control patients
      were investigated by ERUS. Rectal wall thickness and layers, ulcers and
      rectovaginal fistulas were evaluated by B-mode ultrasound. Power Doppler imaging
      was used to evaluate the vascularity of the rectal wall using a semiquantitative
      score. Disease activity was calculated according to the National Cancer Institute
      Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0). Imaging findings
      for patients with mild and severe CRP were compared. For 30 patients in the
      control group, the average maximum thickness of the rectal wall was 3.07 +/- 0.73
      mm, with all exhibiting typical wall stratification and level 0 vascularity. For
      the 40 CRP patients, there was marked thickening of the rectal wall (average
      thickness = 9.42 +/- 1.94 mm), which was significantly thicker than in the
      control group (p < 0.05). The rectal walls of the mild group were significantly
      thinner than those of the severe group (8.71 +/- 1.67 mm vs. 10.00 +/- 2.00 mm, p
      < 0.05). Among the 22 severe cases, 19 cases (19/22, 86.4%) exhibited hyper
      vascularity (level IV) or blurred wall stratification (including hypo-echoic
      submucosa, ulcer and fistula); 12 of the 18 mild cases (166.7%) exhibited a
      vascularity of level III and typical wall stratification. A significant
      association (p < 0.05) was observed between stratification and vascularity of the
      rectal wall and CRP activity. When ERUS findings of blurred rectal wall
      stratification or increasing vascularity (level IV) were used to evaluate CRP
      activity, the sensitivity was 86.4% (95% confidence interval: 64.0-96.4) and the
      specificity was 66.7% (95% confidence interval: 41.2-85.6). Thickening of the
      rectal wall, blurred wall stratification and increased vascularity are
      characteristic ERUS findings of CRP. ERUS is helpful in the comprehensive
      evaluation of disease activity and may provide objective evidence during
      treatment planning and follow-up.

PMID- 28755791
TI  - Histology-Based Assessment of Sonazoid-Enhanced Ultrasonography for the Diagnosis
      of Liver Metastasis.
AB  - This retrospective study aimed to assess the diagnostic performance of contrast
      enhanced ultrasound with Sonazoid (S-CEUS) for liver metastasis. We enrolled in
      this study 98 patients with 148 histologically proven liver lesions, with 121
      metastases and 27 non-metastases. The S-CEUS technique showed sensitivity in
      95.0% (115 of 121), specificity in 44.4% (12 of 27) and accuracy in 85.8% (127 of
      148) for the diagnosis of metastasis. Higher body mass index had a negative
      influence on the positive predictive value and accuracy, and a greater depth of
      the lesion had a negative influence on the accuracy. The management was changed
      in 8 patients (8.2%) because of S-CEUS findings. In conclusion, the addition of S
      CEUS may offer a great benefit by improvement of the quality of diagnosis and
      management for patients with cancer who have a tentative diagnosis of liver
      metastasis by contrast-enhanced computed tomography.

PMID- 28755792
TI  - Quantifying Image Quality Improvement Using Elevated Acoustic Output in B-Mode
      Harmonic Imaging.
AB  - Tissue harmonic imaging has been widely used in abdominal imaging because of its
      significant reduction in acoustic noise compared with fundamental imaging.
      However, tissue harmonic imaging can be limited by both signal-to-noise ratio and
      penetration depth during clinical imaging, resulting in decreased diagnostic
      utility. A logical approach would be to increase the source pressure, but the in
      situ pressures used in diagnostic ultrasound are subject to a de facto upper
      limit based on the U.S. Food and Drug Administration guideline for the mechanical
      index (<1.9). A recent American Institute of Ultrasound in Medicine report
      concluded that an effective mechanical index <=4.0 could be warranted without
      concern for increased risk of cavitation in non-fetal tissues without gas bodies,
      but would only be justified if there were a concurrent improvement in image
      quality and diagnostic utility. This work evaluates image quality differences
      between normal and elevated acoustic output hepatic harmonic imaging using a
      transmit frequency of 1.8 MHz. The results indicate that harmonic imaging using
      elevated acoustic output leads to modest improvements (3%-7%) in contrast-to
      noise ratio of hypo-echoic hepatic vessels and increases in imaging penetration
      depth on the order of 4 mm per mechanical index increase of 0.1 for a given focal
      depth. Difficult-to-image patients who suffer from poor ultrasound image quality
      exhibited larger improvements than easy-to-image study participants.

PMID- 28755793
TI  - Transient central retinal artery occlusion after sub-tenon's anaesthesia: Is it a
      safe technique?

PMID- 28755794
TI  - Big data opportunities for social behavioral and mental health research.

PMID- 28755795
TI  - Therapeutic use of transferrin to modulate anemia and conditions of iron
      toxicity.
AB  - As the main iron transporter, transferrin delivers iron to target tissues like
      the bone marrow for erythropoiesis. Also, by binding free iron, transferrin
      prevents formation of reactive oxygen species. Transferrin deficiency due to
      congenital hypotransferrinemia is characterized by anemia as well as oxidative
      stress related to toxic free iron. Transferrin supplementation may be beneficial
      in two ways. First, transferrin can correct anemia by modulating the amount of
      iron that is available for erythropoiesis. This is obvious for patients that
      suffer from hypotransferrinemia, but may also have beneficial effects for beta
      thalassemia patients. Second, under conditions of iron overload, transferrin
      reduces oxidative stress by binding free iron in the circulation and in tissues.
      Hereby, transferrin protects the host against the reactive oxygen species that
      can be formed as a consequence of free iron. This beneficial effect is shown in
      hematological patients undergoing chemotherapy and stem cell transplantation.
      Transferrin may also be beneficial in lung injury, ischemia-reperfusion injury
      and hypomyelination. This review summarizes the preclinical and clinical data on
      the efficacy of exogenous transferrin administration to modulate certain forms of
      anemia and to prevent the toxic effects of free iron. Thereby, we show that
      transferrin has promising therapeutic potential in a wide variety of conditions.

PMID- 28755796
TI  - Significant association of inflammation grade with the number of Langerhans cells
      in odontogenic keratocysts.
AB  - BACKGROUND/PURPOSE: Langerhans cells (LCs) are antigen-presenting cells. This
      study assessed the LC counts in odontogenic keratocysts (OKCs). METHODS: The LC
      numbers in the lining epithelia and subepithelial connective tissues were counted
      at 60 OKC sites without inflammation, 39 OKC sites with mild/moderate
      inflammation, and 13 OKC sites with severe inflammation from 60 OKC specimens
      immunostained with anti-S100 antibodies. RESULTS: The mean LC counts in the
      lining epithelia and subepithelial connective tissues increased significantly
      from no inflammation (0.5 +/- 0.4 and 0.7 +/- 0.6 cell/high-power field or HPF,
      respectively) through mild/moderate inflammation (5.9 +/- 2.7 and 5.0 +/- 3.5
      cells/HPF, respectively) to severe inflammation OKC sites (14.7 +/- 5.3 and 13.3
      +/- 6.8 cells/HPF, respectively; all P-values < 0.001). OKC sites with
      inflammation had thicker lining epithelia than those without inflammation.
      Moreover, the mean LC counts in the lining epithelia and subepithelial connective
      tissues of OKCs were significantly higher in the thicker lining epithelium (>100
      MUm) group (7.7 +/- 5.6 and 6.5 +/- 5.8 cells/HPF, respectively) than in the
      thinner lining epithelium (? 100 MUm) group (1.0 +/- 2.0 and 1.4 +/- 2.6
      cells/HPF, respectively; both P-values < 0.001). CONCLUSION: A significant
      association of inflammation grade with the number of LCs in OKCs is found. The
      paucity of finding LCs in the lining epithelia of OKCs without inflammation
      indicates the loss of immunosurveillance ability against the OKC lining
      epithelial cells; this can explain why OKCs have aggressive clinical behavior, a
      great growth potential, and a high recurrence rate.

PMID- 28755797
TI  - Internal iliac artery injury due to intrapelvic migration of infected acetabular
      reconstruction cage with hook: A case report.

PMID- 28755798
TI  - Detecting masses in dense breast using independent component analysis.
AB  - Breast cancer is the second type of cancer that most affects women in the world,
      losing only for non-melanoma skin cancer. Breast density can hinder the location
      of masses, especially in early stages. In this work, the use of independent
      component analysis for detecting lesions in dense breasts is proposed. Several
      works suggest the use of computer aided diagnosis (CAD), increasing sensitivity
      to over 90% in detecting cancer in nondense breasts, however there are few
      published studies about detecting in dense breasts. To analyse its efficiency in
      relation to other segmentation techniques, we compare the performance with
      principal component analysis. To measure the quality of the segmentation obtained
      by the two methods, an area overlay measure will be used. To verify if there was
      any difference between the results of the proposed methods in the detection of
      lesions in nondense breasts and in dense breasts, a statistic test for two
      proportions was used. Experimental results on the Mini-MIAS and DDSM database
      showed an accuracy of 92.71% in detecting masses in nondense and 79.17% in dense
      breasts. All experiments showed that the ICA filters have a better performance
      for detect lesions in dense breast, compared with PCA. Contrary to previous
      works, our experiments showed that there is actually a significant difference
      between the detection of masses in dense and nondense breasts. This study can
      help specialist to detect lesions in dense breast.

PMID- 28755799
TI  - [Professional practice evaluation of injectable drug preparation and
      administration in neonatology].
AB  - AIM: Adverse drug events are a daily concern in neonatology departments. The aim
      of this study was to assess the professional practices of preparation and
      administration of injectable forms of medications in neonatology. MATERIALS AND
      METHODS: A professional practice evaluation with regard to the preparation and
      administration of various injectable forms of medications in different
      neonatology units within a given department was conducted by a pharmacy intern
      based on an assessment grid comprising ten criteria. Following an initial
      assessment, the results were presented to the care team, which validated the
      corrective measures put forward by a multiprofessional work group. A second
      assessment was conducted following the same methodology. RESULTS: Fifty of the
      department's 76 pediatric nurses were assessed during the first round of the
      audit and 21 during the second round. Two improvement priorities were identified:
      taking account of the dead volume of medication in needles and syringe hubs,
      together with complete identification of syringes used to administer medication.
      During the second round, these two aspects were improved, progressing from 38% to
      100% and from 59% to 89%, respectively. CONCLUSION: To improve drug
      administration in neonatology and consequently, to improve patient safety,
      professional practice evaluation is an essential tool that requires close
      collaboration between the paramedical team, physicians and pharmacists. Its main
      value lies in the mobilization of the entire team around the subject in question,
      hence generating improved understanding and application of corrective measures.

PMID- 28755800
TI  - [Parental mourning after a perinatal loss].
AB  - The loss of a close friend or relative is always an ordeal. When this loved one
      is a baby, born or even unborn, a number of specific aspects have been reported
      by parents and researchers. The specificities of perinatal mourning have been
      progressively recognized since the 1970s, with increasing literature on this
      topic. Its complexity should be acknowledged by healthcare professionals who cope
      with perinatal loss, to allow them to offer adapted familial support. This paper
      is written by a mother, a founding member of a French nonprofit organization
      supporting parents in case of a prenatal or postnatal life-limiting disorder
      (Association SPAMA, soins palliatifs et accompagnement en maternite) with an
      internet support forum and a neonatologist involved in research with parents
      after the loss of their baby. It attempts to describe how parents experience this
      situation and how palliative care provides a source of inspiration to families
      and helps them give meaning to these situations.

PMID- 28755802
TI  - When to remove the urethral catheter after endoscopic realignment of traumatic
      disruption of the posterior urethra?
AB  - OBJECTIVE: To detect the optimal time for urethral stent removal after endoscopic
      urethral realignment and its effect on the incidence of development of urethral
      stricture. PATIENTS AND METHODS: Eighteen patients underwent endoscopic urethral
      realignment after traumatic disruption of the posterior urethra. Post-operative
      urethroscopy was done using the flexible cystoscope to assess progress of
      urethral healing. The urethral Foley catheter that served as a stent and for
      urine drainage was removed only when complete mucosal healing was observed by
      flexible urethroscopy. There was a post-operative follow-up period of 12
      36months. Uroflowmetry was performed at the end of the follow-up period. RESULTS:
      Endoscopy 6weeks after realignment showed 50-75% mucosal epithelialization at the
      site of urethral disruption in all patients. Epithelialization was complete at
      9weeks in 15/18 patients (83%) and at 12weeks in the remaining 3 patients (17%).
      One patient (5.6%) developed a mild symptomatic stricture 5months post stent
      removal that was successfully treated by a single session of visual urethrotomy.
      All 18 patients had normal uroflowmetry readings at 12-36months after
      realignment. CONCLUSIONS: Urethral stenting should be continued till mucosal
      healing at the site of urethral disruption became complete. Removal of the stent
      at this optimal time decreases the incidence of post-operative urethral
      stricture. Flexible urethroscopy was a safe procedure for post-operative follow
      up of endoscopic urethral realignment to assess the progress and completion of
      mucosal healing at the site of realignment. LEVEL OF EVIDENCE: 4.

PMID- 28755801
TI  - International trends in antipsychotic use: A study in 16 countries, 2005-2014.
AB  - The objective of this study was to assess international trends in antipsychotic
      use, using a standardised methodology. A repeated cross-sectional design was
      applied to data extracts from the years 2005 to 2014 from 16 countries worldwide.
      During the study period, the overall prevalence of antipsychotic use increased in
      10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic
      use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000).
      In children and adolescents (0-19 years), antipsychotic use ranged from 0.5/1000
      (Lithuania) to 30.8/1000 (Taiwan). In adults (20-64 years), the range was
      2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older
      adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to
      149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations
      (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)).
      Quetiapine, risperidone, and olanzapine were most frequently prescribed.
      Prevalence and patterns of antipsychotic use varied markedly between countries.
      In the majority of populations, antipsychotic utilisation and especially the use
      of atypical antipsychotics increased over time. The high rates of antipsychotic
      prescriptions in older adults and in youths in some countries merit further
      investigation and systematic pharmacoepidemiologic monitoring.

PMID- 28755803
TI  - Sleep in infants with congenital myasthenic syndromes.
AB  - BACKGROUND AND OBJECTIVES: Infants with congenital myasthenic syndrome (CMS) are
      at risk of brief resolved unexplained event (BRUE) and sleep-disordered
      breathing. The aim of the study was to explore sleep in infants with CMS with a
      particular focus on heart rate (HR) variability. METHODS: Overnight polygraphy
      was performed and HR variations associated with respiratory events were analysed.
      Bradycardia and tachycardia were defined as a variation of HR of +/-10 bpm from
      baseline and analysed as events/hour. RESULTS: The data of 5 infants with CMS
      were analysed. Two patients had known mutations (COLQ and RAPSN). One patient had
      a tracheostomy. The apnoea-hypopnoea index (AHI) was abnormal in all the patients
      (range 2.8-47.7 events/h), with the highest AHI being observed in the 3 youngest
      infants. Nocturnal transcutaneous gas exchange was normal in all patients except
      the tracheostomised patient. Mean HR was 114 +/- 23 bpm with a mean HR index of
      4.5 +/- 4.3 events/h. The amplitudes of HR variations (bradycardia or
      tachycardia) were around 15-20 bpm, regardless of the type of respiratory event,
      and comparable between patients. No correlations were found between HR indexes or
      variations and the type and mean duration of respiratory events. Ventilatory
      support was initiated in 3 infants immediately after the sleep study because of a
      high AHI and/or nocturnal hypoventilation. CONCLUSIONS: All 5 infants had an
      abnormal AHI with younger infants having the highest AHI. Three infants required
      ventilatory support after the polygraphy, underlining its clinical usefulness. No
      significant abnormalities of HR were observed during the sleep studies.

PMID- 28755804
TI  - A new index to simplify the screening of hypertension in overweight or obese
      youth.
AB  - BACKGROUND AND AIMS: Hypertension (HTH) is a frequent complication in pediatric
      obesity. To simplify the screening of HTH in overweight/obese (Ow/Ob) youth, we
      compared the performance of a new index (High Blood Pressure index, HBPi) with
      respect to the standard criteria of the IV Report [systolic BP (SBP) and/or
      diastolic BP (DBP) >=95th percentile for age, gender and height]. We also
      compared the performance of HBPi with other simplified indices such as the
      BP/height ratio and the absolute height-specific BP thresholds. Ten pediatrics'
      outpatient centers participating in the "CARdiometabolic risk factors in ITALY
      study" provided medical records of 4225 Ow/Ob children and adolescents (age 6-16
      years). METHODS AND RESULTS: Centers were divided into two groups: training set
      (TS) (n = 2204 participants) and validation set (VS) (n = 2021 participants). The
      simplified HBPi (mmHg) was: (SBP/2 + DBP/10) - age + (1 * female gender). In the
      TS, a HBPi value >=57 mmHg in both children and adolescents had high sensitivity
      (0.89), specificity (0.97), positive (0.89) and negative (0.97) predictive values
      in classifying youth at high risk of HTN compared with the IV Report. In the VS,
      the HBPi showed a better performance than high levels of BP/height ratio and
      height-specific BP thresholds in classifying individuals at risk of HTN: area
      under curves 0.95 (0.93-0.96), 0.80 (0.78-0.82), 0.76 (0.74-0.79), respectively;
      specificities 0.95 (0.94-0.96), 0.69 (0.67-0.72), 0.60 (0.57-0.62), respectively.
      CONCLUSIONS: HBPi, combining SBP and DBP, gender and age, may help pediatricians
      to implement HTN screening in Ow/Ob youth.

PMID- 28755805
TI  - Italian national guidelines for the screening of gestational diabetes: Time for a
      critical appraisal?
AB  - BACKGROUND AND AIM: In 2011, the Italian National Health System guidelines
      introduced a selective screening for gestational diabetes (GDM) based on risk
      factors, recommending early evaluation in high risk women. The present study
      examined to which extent guidelines are applied, and analyzed the effectiveness
      of GDM diagnosis according to risk profile. METHODS AND RESULTS: We analyzed 1338
      pregnant women, consecutively screened for GDM with a 75 g OGTT between January
      2013 and December 2015, according to national guidelines. Diagnosis of GDM was
      based on IADPSG/WHO 2013 criteria. As many as 14.4% of screened women was at high
      risk, 64% at medium, 21.6% did not have any risk factor. Only 50% of high-risk
      women were appropriately screened at 16th-18th gestational weeks; 28% of them
      repeated the OGTT due to NGT. The overall prevalence of GDM was 39.9%, higher in
      high risk women (67% vs. 40% medium risk vs. 22% low risk; p < 0.0001). An early
      GDM diagnosis was performed in 40.7% of high-risk women. In low risk women,
      gestational weight gain at the screening time was independently associated with
      GDM. CONCLUSIONS: The recommendations for the screening of GDM are still
      insufficiently implemented, especially for early evaluation in high risk women.
      Considering the high proportion of early GDM diagnosis, the poor adherence to
      screening recommendation may result in late diagnosis of GDM. Finally, our
      finding of a 22% prevalence of GDM among low risk women suggests the need to
      consider additional risk factors, such as excessive weight gain during pregnancy.

PMID- 28755806
TI  - Physical activity and blood pressure in 10,000 Mediterranean adults: The EPIC
      Florence cohort.
AB  - BACKGROUND AND AIMS: The relevant role of physical activity (PA) in
      cardiovascular risk prevention is widely agreed. We aimed to evaluate, in a large
      Mediterranean population, the influence of PA on systolic (SBP) and diastolic
      blood pressure (DBP), taking into account individual characteristics and
      lifestyle habits. METHODS AND RESULTS: In the Florence section of the European
      Prospective Investigation into Cancer and Nutrition 10,163 individuals, 35-64
      years, without a previous diagnosis of hypertension were recruited. Information
      on occupational and leisure-time PA and blood pressure were collected at
      recruitment, together with data on lifestyle, dietary habits and anthropometry.
      Multivariate regression models were applied to evaluate the effect of total,
      occupational and leisure-time PA on SBP and DBP. Mean values of SBP and DBP in
      the study subjects were 124.4 (SD 15.6) and 79.7 mmHg (SD 9.4), respectively.
      Overall, a total PA index and an index including cycling, fitness and
      occupational PA (Cambridge index) were inversely associated with DBP (beta -0.87,
      p-value 0.02 actives vs inactives, p for trend 0.02 and beta -0.84, p value 0.003
      actives vs inactives, p for trend 0.002, respectively), while SBP was associated
      only with the latter index (beta -1.14, p-value 0.01 actives vs inactives, p for
      trend 0.006). An inverse association emerged between manual/heavy manual
      occupation and DBP (p 0.02, ref sedentary/standing occupation) and between
      increasing cycling activity and SBP (p for trend 0.04). CONCLUSIONS: In this
      large cohort of Mediterranean adults without a diagnosis of hypertension we
      confirm the role of overall PA in modulating SBP and DBP values. Cycling and
      manual occupations were associated with lower DBP values.

PMID- 28755807
TI  - Cholesterol lowering treatment restores blood global DNA methylation in chronic
      kidney disease (CKD) patients.
AB  - BACKGROUND AND AIMS: Chronic kidney disease (CKD) is characterized by increased
      oxidative stress (OS). In consideration of the well-known link between OS and DNA
      methylation we assessed DNA methylcytosine (mCyt) concentrations in CKD patients
      at baseline and during cholesterol lowering treatment. METHODS AND RESULTS: DNA
      methylation and OS indices (malonyldialdehyde, MDA; allantoin/uric acid ratio,
      All/UA) were measured in 30 CKD patients randomized to three cholesterol lowering
      regimens for 12 months (simvastatin 40 mg/day, ezetimibe/simvastatin 10/20
      mg/day, or ezetimibe/simvastatin 10/40 mg/day) and 30 age- and sex-matched
      healthy controls. DNA methylation was significantly lower in CKD patients vs.
      controls (4.06 +/- 0.20% vs. 4.27 +/- 0.17% mCyt, p = 0.0001). Treatment
      significantly increased mCyt DNA concentrations in all patients (4.06 +/- 0.04%
      at baseline; 4.12 +/- 0.03% at 4 months; 4.17 +/- 0.03% at 8 months; and 4.20 +/-
      0.02% at 12 months, p = 0.0001 for trend). A trend for a greater effect on DNA
      methylation was observed with combined treatment ezetimibe/simvastatin 10/40
      mg/day (+5.2% after one year treatment). The treatment-associated mCyt increase
      was significantly correlated with the concomitant reduction in MDA concentrations
      and All/AU ratios. CONCLUSION: Our results demonstrate that CKD patients have a
      lower degree of DNA methylation and that cholesterol lowering treatment restores
      mCyt DNA concentrations to levels similar to healthy controls. The treatment
      associated increase in DNA methylation is correlated with a concomitant reduction
      in OS markers. The study was registered at clinicaltrials.gov (NCT00861731).

PMID- 28755808
TI  - Potential role of CXCL10/CXCR3 signaling in the development of morphine tolerance
      in periaqueductal gray.
AB  - Tolerance to morphine antinociception hinders its long-term use in clinical
      practice. Interaction between neuron and microglia has been proved to play
      critical role in the mechanism of morphine tolerance, while CXCL10/CXCR3
      signaling has been implicated in neuron-glia signaling and morphine analgesia.
      This study aims to investigate whether CXCL10/CXCR3 signaling in periaqueductal
      gray (PAG) contributes to the development of morphine tolerance by modulating
      neuron-microglia interaction. The results showed that the expressions of CXCR3
      and CXCL10 were gradually increased in parallel with repeated morphine
      administration and activation of microglia. CXCR3 was co-localized with neuronal
      marker NeuN, while CXCL10 was derived from microglia. Microglia inhibitor
      minocycline significantly attenuated the expression of CXCL10, besides, both
      minocycline and CXCR3 inhibitor alleviated the development of morphine tolerance.
      Taken together, our study provided the evidence that CXCL10/CXCR3 signaling in
      PAG is involved in the development of morphine analgesic tolerance via neuron
      microglia interaction.

PMID- 28755809
TI  - Prevention through policy: Urban macroplastic leakages to the marine environment
      during extreme rainfall events.
AB  - The leakage of large plastic litter (macroplastics) into the ocean is a major
      environmental problem. A significant fraction of this leakage originates from
      coastal cities, particularly during extreme rainfall events. As coastal cities
      continue to grow, finding ways to reduce this macroplastic leakage is extremely
      pertinent. Here, we explore why and how coastal cities can reduce macroplastic
      leakages during extreme rainfall events. Using nine global cities as a basis, we
      establish that while cities actively create policies that reduce plastic
      leakages, more needs to be done. Nonetheless, these policies are economically,
      socially and environmentally cobeneficial to the city environment. While the lack
      of political engagement and economic concerns limit these policies, lacking
      social motivation and engagement is the largest limitation towards implementing
      policy. We recommend cities to incentivize citizen and municipal engagement with
      responsible usage of plastics, cleaning the environment and preparing for future
      extreme rainfall events.

PMID- 28755810
TI  - Bacterial community structure in the intertidal biofilm along the Yangtze
      Estuary, China.
AB  - In this study, the 16S rRNA-based Illumina MiSeq sequencing was used to
      investigate the bacterial community structure and composition of intertidal
      biofilm taken along the Yangtze Estuary. The results showed that 680,721 valid
      sequences of seven samples were assigned to 147,239 operational taxonomic units,
      which belonged to 49 phyla, 246 family and 314 genera. Compared to other studies
      on water and sediments in the study area, biofilms showed highest index of
      bacterial diversity and abundances. At different taxonomic levels, both dominant
      taxa and their abundances varied among the seven samples, with Proteobacteria as
      the dominant phylum in general. Principal component analysis and cluster analysis
      revealed that bacterial communities at WSK differed from those at other sampling
      sites. Salinity, dissolved oxygen, pH and nutrients were the vital environmental
      factors to influence the bacterial community structure of biofilms. These results
      may provide a new insight into the microbial ecology in estuarine environments.

PMID- 28755811
TI  - Ambient noise dynamics in a heavy shipping area.
AB  - The management of underwater noise within the European Union's waters is a
      significant component (Descriptor 11) of the Marine Strategy Framework Directive
      (MSFD). The indicator related to continuous noise, is the noise levels in two one
      third octave bands centered at 63Hz and 125Hz. This paper presents an analysis of
      underwater noise in the Celtic Sea, a heavy shipping area which also hosts the
      seasonal Ushant thermal front. In addition to the MSFD recommended frequency
      bands, the analysis was extended to lower and upper frequency bands. Temporal and
      spatial variations as well as the influence of the properties of the water column
      on the noise levels were assessed. The noise levels in the area had a high
      dynamic range and generally exceeded 100dB re 1MUPa. Finally, the results
      highlighted that oceanic mooring must be designed to minimize the pseudo-noise
      and consider the water column physical properties.

PMID- 28755812
TI  - Increasing contribution of coccolithophorids to the phytoplankton in the
      northeastern Black Sea.
AB  - During 2005-2011, 418 phytoplankton samples were collected in Novorossiysk and
      Tuapse ports and near the resort cities of Anapa and Gelendzhik in the
      northeastern Black Sea. The maximal values of both abundance and biomass of
      phytoplankton related to high nutrient concentration, probably due to
      anthropogenic load, were observed at Novorossiysk (5.82*105cells/l, 1.492g/m3);
      in other bays values were about three times lower. The annual cycle included two
      to four phytoplankton abundance peaks. Emiliania huxleyi was the most abundant
      coccolithophorid (1.15*105cells/l offshore and 2.20*104cells/l in bays and
      ports). In spring-summer it contributed up to 90% of the phytoplankton abundance
      offshore. The maximal abundance of E. huxleyi was observed offshore of Gelendzhik
      (up to 1.32*106cells/l); the minimum was in the coastal zone in the port of
      Novorossiysk (on average 7.7*103cells/l). Generally, the species appears to avoid
      eutrophic waters.

PMID- 28755813
TI  - Editorial overview: Cell regulation: New insights into the versatile regulatory
      processes governing bacterial life.

PMID- 28755814
TI  - Biomechanical assessment of the aortic root using novel force transducers.
AB  - In recent years the use of valve sparing techniques has become more common in
      selected patients with aortic valve insufficiency. However, limited experimental
      research has been performed to document the biomechanical effect of these
      techniques. One experimental platform is to evaluate how the normal physiological
      aortic root forces are altered or re-established after the surgical intervention.
      Hence, the aim of this project was to develop new implantable force transducers
      for a biomechanical description of various aortic root repair techniques. Two
      novel force transducers were developed. Both transducers were manufactured using
      rapid prototyping and were instrumented with miniature strain gauges. Before
      implantation both transducers were calibrated using a dedicated setup, yielding
      very linear correlation between the applied load and transducer output. The
      developed force transducers were implanted and tested in an 80kg porcine model.
      In the post-cardioplegic heart, the peak annular forces varied in the range of 2
      4N and the commissural forces varied from 0.4 to 0.8N with a left ventricular
      pressure of 111mmHg. In conclusion, the two new force transducers to measure
      forces in the aortic root have successfully been developed. With these new
      devices a novel versatile and direct force measurement system has been provided.

PMID- 28755815
TI  - Normalized patellofemoral joint reaction force is greater in individuals with
      patellofemoral pain.
AB  - Patellofemoral pain is a disabling, highly prevalent pathology. Altered
      patellofemoral contact forces are theorized to contribute to this pain.
      Musculoskeletal modeling has been employed to better understand the etiology of
      patellofemoral pain. Currently, there are no data on the effective quadriceps
      moment arm for individuals with patellofemoral pain, forcing researchers to apply
      normative values when modeling such individuals. In addition, the ratio of
      patellofemoral reaction force to quadriceps force is often used as a surrogate
      for patellofemoral joint contact force, ignoring the fact that the quadriceps
      efficiency can vary with pathology and intervention. Thus, the purposes of this
      study were to: (1) quantify the effective quadriceps moment arm in individuals
      with patellofemoral pain and compare this value to a control cohort and (2)
      develop a novel methodology for quantifying the normalized patellofemoral joint
      reaction force in vivo during dynamic activities. Dynamic MR data were captured
      as subjects with patellofemoral pain (30F/3M) cyclically flexed their knee from
      10 degrees  to 40 degrees . Data for control subjects (29F/9M) were taken from a
      previous study. The moment arm data acquired across a large cohort of individuals
      with patellofemoral pain should help advance musculoskeletal modeling. The
      primary finding of this study was an increased mean normalized patellofemoral
      reaction force of 14.9% (maximum values at a knee angle of 10 degrees ) in
      individuals with patellofemoral pain. Understanding changes in the normalized
      patellofemoral reaction force with pathology may lead to improvements in clinical
      decision making, and consequently treatments, by providing a more direct measure
      of altered patellofemoral joint forces.

PMID- 28755816
TI  - Analysis of the tennis racket vibrations during forehand drives: Selection of the
      mother wavelet.
AB  - The time-frequency analysis of the tennis racket and hand vibrations is of great
      interest for discomfort and pathology prevention. This study aimed to (i) to
      assess the stationarity of the vibratory signal of the racket and hand and (ii)
      to identify the best mother wavelet to perform future time-frequency analysis,
      (iii) to determine if the stroke spin, racket characteristics and impact zone can
      influence the selection of the best mother wavelet. A total of 2364 topspin and
      flat forehand drives were performed by fourteen male competitive tennis players
      with six different rackets. One tri-axial and one mono-axial accelerometer were
      taped on the racket throat and dominant hand respectively. The signal
      stationarity was tested through the wavelet spectrum test. Eighty-nine mother
      wavelet were tested to select the best mother wavelet based on continuous and
      discrete transforms. On average only 25+/-17%, 2+/-5%, 5+/-7% and 27+/-27% of the
      signal tested respected the hypothesis of stationarity for the three axes of the
      racket and the hand respectively. Regarding the two methods for the detection of
      the best mother wavelet, the Daubechy 45 wavelet presented the highest average
      ranking. No effect of the stroke spin, racket characteristics and impact zone was
      observed for the selection of the best mother wavelet. It was concluded that
      alternative approach to Fast Fourier Transform should be used to interpret tennis
      vibration signals. In the case where wavelet transform is chosen, the Daubechy 45
      mother wavelet appeared to be the most suitable.

PMID- 28755817
TI  - A need for accuracy during bibliometric assessments.

PMID- 28755818
TI  - Reinstatement of the Mexico City policy and its impact on global health.

PMID- 28755819
TI  - Descriptive Epidemiology, Medical Evaluation, and Outcomes of Rock Climbing
      Injuries.
AB  - OBJECTIVE: To gather epidemiologic data on injury type, treatment, and recovery
      from rock climbing injuries. METHODS: Design: retrospective cross-sectional
      study. SETTING: web-based survey. PARTICIPANTS: rock climbers who sustained a
      climbing-related injury during the prior 24 months. Criteria for inclusion: aged
      >=18 years; participation in rock climbing at least 4 times per year in the
      United States. INTERVENTIONS: none. MAIN OUTCOME MEASURES: percentage of injured
      climbers seeking medical care, providers seen, subspecialty referral, development
      of chronic problems, factors affecting return to climbing, injuries by climbing
      type, body region, and injury type. RESULTS: Data were collected over a 60-day
      period using the Research Electronic Data Capture (REDCap) survey system. Seven
      hundred and eight surveys were collected from 553 male and 155 female climbers.
      Thirteen hundred ninety seven injuries were reported, and 975 injuries were
      suitable for analysis. The most common provider initially seen was a primary care
      provider. Subspecialty referral was commonly obtained. Injury patterns differed
      by climbing type. The percentage of respondents that returned to climbing before
      their injury was fully healed was 51.1%, and 44.9% of respondents developed
      chronic problems related to their climbing injury. Twenty-eight percent of
      respondents were unable to return to their previous level of climbing
      performance. Several factors were associated with delayed recovery from climbing
      injury. CONCLUSIONS: A significant number of climbers sought healthcare after
      injury. A majority of climbers who sought treatment were referred to
      subspecialist providers. About one-half of climbers were symptomatic when they
      returned to climbing and developed chronic problems after injury. Factors
      associated with slower return to climbing included increasing age, smoking,
      fractures, and surgery.

PMID- 28755820
TI  - Prolonged Coagulopathy, Ecchymoses, and Microangiopathic Hemolytic Anemia
      Following Hump-Nosed Pit Viper (Hypnale hypnale) Bite in Sri Lanka.
AB  - A 74-year-old previously healthy woman was bitten by a hump-nosed pit viper
      (Hypnale hypnale) at dusk causing incoagulable blood lasting for 6 days. Further,
      she developed ecchymoses over her forearms, upper arms, hands, and lower back on
      day 4 after the snakebite, and microangiopathic hemolytic anemia (MAHA). Features
      of this nature are rare after hump-nosed pit viper bite.

PMID- 28755821
TI  - Promoting High-Quality Research.

PMID- 28755822
TI  - Familial digital arthropathy-brachydactyly: An infrequent cause of joint
      deformity in adolescents.

PMID- 28755823
TI  - Identification of hypophosphatasia in a clinical setting: Clinical manifestations
      and diagnostic recommendations in adult patients.

PMID- 28755824
TI  - Primary syphilis in a secondary stage.

PMID- 28755825
TI  - Mobbing in health workplace.

PMID- 28755826
TI  - Persistent increase in troponin levels in a patient without evidence of ischaemic
      heart disease.

PMID- 28755827
TI  - Association between environmental factors and hospitalisations for bronchiectasis
      in Badalona, Barcelona, Spain (2007-2015).
AB  - INTRODUCTION: The relationship between environmental factors and the exacerbation
      of respiratory diseases has been widely studied. However, there are no studies
      examining the relationship between these factors and bronchiectasis
      exacerbations. Our objective was to analyse the association between various
      environmental factors and hospitalisation for bronchiectasis. MATERIAL AND
      METHODS: This was a retrospective observational study conducted at two hospitals
      in Badalona (Barcelona). The number of hospital admissions for exacerbation of
      bronchiectasis between 2007 and 2015 was obtained. Through multiple regression we
      analysed the relationship between the number of exacerbations and mean monthly
      values of temperature, SO2, NO, NO2, O3 and CO. RESULTS: Temperature, SO2, NO,
      NO2, O3 and CO were significantly associated with an increase in admissions due
      to exacerbation of bronchiectasis. By controlling the effect of temperature on
      the pollution variables, only SO2 maintained statistical significance (P=.008).
      CONCLUSION: We have detected an increase in hospital admissions for exacerbation
      of bronchiectasis with increases in the atmospheric concentration of SO2 and the
      decrease in temperature. Prospective studies with different geographical
      locations to confirm these results are needed.

PMID- 28755828
TI  - Patientensicherheit ist in einem soziotechnischem System eine gemeinsame Aufgabe.

PMID- 28755829
TI  - [Care and optimal management of the face- and neck-lift patients].
AB  - Surgical and case management for patients demanding a face- and neck-lift are
      very important. The purpose of this paper is to help the plastic surgeons with
      information and recommendations useful for the best medical care of patients
      requiring a face- and neck-lift. The first consultation is the most important
      contact with the patient. The preoperative discussion helps to define patient
      demands and to evaluate eventual contraindications for surgery. The clinical exam
      and patient requirements are useful in the construction of the therapeutic
      proposition. This proposition is then confronted with patients' expectations and
      demands. The confrontation between the surgical proposition and patients'
      expectations allows to evaluate if it is appropriate, or not, to operate. At the
      end of the first consultation, the patient receives the information sheets of the
      French Plastic Surgery Society (SOFCPRE) according to the proposed surgical
      treatment. The second consultation makes it possible to verify the pertinence of
      the surgical act, to reiterate the preoperative recommendations, to confirm that
      the information given to the patient was well understood and to obtain the
      written consent from the patient. The written consent should include the fact
      that the patient received the information sheets of the SOFCPRE, that they were
      read and understood, and that the surgeon has transmitted the necessary
      information in order for the patient to take an informed and free decision to
      pursue with the surgery. The follow-up after surgery is as important as the
      surgery itself. In some cases, cosmetic gestures can be performed in the
      following months to obtain the best results possible and the highest
      satisfaction. The face- and neck-lift is an "adventure" for the patients and the
      postoperative difficulties should not be underestimated. However, the caring and
      professional support of the plastic surgeon and the support of someone of the
      patients' entourage can help the patient overcome this stage, and obtain a
      maximum benefit after this operation.

PMID- 28755830
TI  - [Dermatofibrosarcoma protuberans: Surgical margins using Slow-Mohs micrographic
      surgery. A clinical retrospective study about 20 cases].
AB  - OBJECTIVES: The main objective of this study is to determine the necessary
      surgical margins to obtain a complete R0 resection for head and neck
      dermatofibrosarcoma protuberans (DFSP) using Slow-Mohs micrographic surgery. The
      secondary objective is to study the recurrence rate of these tumors. PATIENTS AND
      METHODS: Slow-Mohs micrographic surgery was used for patients included between
      2005 and 2015 at Bordeaux universitary hospital. For each patient the age, the
      sex and death occurrence, the initial surgical margins, the surgical margins for
      complete R0 resection, the occurrence of local or general recurrence during
      follow-up were reported. Surgery was realized under local anesthesia. The closure
      of the tumor site was realized secondarily using a skin graft or local flap.
      RESULTS: Twenty patients were included in the study. Initial surgical margins
      were 10mm (9 patients) or 15mm (11 patients). Complete resection was obtained
      from the first surgery for fifteen patients (75%). The average surgical margin
      for a complete R0 resection was 15,25+/-5,7mm (10-25). None of the patients
      presented recurrences during the entire follow-up (38 months) CONCLUSION: A
      complete R0 resection of head and neck DFSP is obtained from the first surgery in
      75% of the cases, with minimum surgical margins (12,75+/-2,55mm) using the Slow
      Mohs micrographic surgery. This allows a reduction of surgical margins and local
      recurrences. This technique provides a preservation of soft-tissues, which plays
      a key role for head and neck surgery.

PMID- 28755831
TI  - [Malignant proliferating trichilemmal cyst of the scalp: A case report].
AB  - BACKGROUND: Proliferating trichilemmal cyst (PTC) is a rare adnexal tumor,
      generally benign, primarily sitting on the scalp of elderly women. About fifty
      cases are reported in the literature. Herein, we describe another one
      particularly aggressive. OBSERVATION: A 70-year-old woman had been showing an
      increase in the size of an occipital cyst for 6years. A cephalic scan and wide
      surgical excision had confirmed the diagnosis of a malignant PTC. Four months
      later, the tumor recurred with regional metastases and intracerebral invasion.
      DISCUSSION: Through our case and based on the literature analyzing, we discuss
      the nosology of PTC and its clinical and histological distinctive elements.
      CONCLUSION: Large studies are needed to better understand the specificities of
      PTC, specially malignant form, but it remains difficult because of its rarity.

PMID- 28755832
TI  - [Serious adverse drug reactions with tramadol reported to the French
      pharmacovigilance database between 2011 and 2015].
AB  - BACKGROUND: Tramadol is an opioid and a serotonin reuptake inhibitor drug. It is
      approved for moderate to severe pain in adults. The aim of this study was to
      assess tramadol safety through a national pharmacovigilance study in France since
      dextropropoxyphen withdrawal in 2011. METHODS: We described all serious adverse
      drug reactions (SADRs) reported with tramadol in adults in the French National
      PharmacoVigilance Database from August 1st, 2011 to December 31st, 2015. RESULTS:
      We identified 1512 SADRs during the study period. The most frequently reported
      SADRs were neurological (29.4%, including troubles of consciousness [13.2%] and
      seizures [6.7%]), psychiatric (22.8%, including confusions [14.6%] and
      hallucinations [7.3%]) and gastrointestinal (17.0%, mostly nausea and vomiting
      [9.6%]). Unexpected SADRs were also reported: hyponatremia, cholestatic
      hepatitis, serotonin syndrome. CONCLUSIONS: This study demonstrates new
      unexpected hepatic and metabolic SADRs. Tramadol alone can induce serotonin
      syndrome in overdose situations.

PMID- 28755833
TI  - Serum antibody response to Moraxella catarrhalis proteins in stringently defined
      otitis prone children.
AB  - BACKGROUND: Moraxella catarrhalis (Mcat) is a frequent pathogen of acute otitis
      media (AOM) in young children. Here we prospectively assessed naturally-induced
      serum antibodies to four Mcat vaccine candidate proteins in stringently defined
      otitis prone (sOP) and non-otitis prone (NOP) children age 6-36months old
      following nasopharyngeal (NP) colonization, at onset of AOM and convalescence
      from AOM. METHODS: Serum IgG and IgM antibody against recombinant Mcat proteins,
      oligopeptide permease A (OppA), outer membrane protein (OMP) CD, hemagglutinin
      (Hag), and PilA clade 2 (PilA2), were quantitated by ELISA. RESULTS: During NP
      colonization by Mcat all four antigens were immunogenic in both sOP and NOP
      children. However, sOP children had lower antibody responses than NOP children
      across age 6-36months, similar to our findings for protein vaccine candidates of
      Streptococcus pneumoniae (Spn) and Nontypeable Haemophilus influenzae (NTHi). sOP
      children displayed a later and lower peak of antibody rise than NOP children for
      all four antigens during NP colonization of Mcat. The age-dependent increase of
      antibody ranked as OppA>Hag5-9>OMP CD>PilA2 in both sOP and NOP children. Lower
      serum antibody levels to the Mcat antigens were measured in sOP compared to NOP
      children at the onset of AOM. We did not find a consistent significant increase
      of antibody at the convalescence phase after an AOM event. CONCLUSIONS: sOP
      children is a highly vulnerable population that mount lower serum antibody
      responses to Mcat candidate vaccine proteins compared to NOP children during
      asymptomatic NP carriage and at onset of AOM.

PMID- 28755834
TI  - Immunogenicity of adenovirus vaccines expressing the PCV2 capsid protein in pigs.
AB  - Porcine circovirus type 2 (PCV2) is the main pathogen of porcine circovirus
      associated disease (PCVAD), causing great economic losses in pig industry. In
      previous study, we constructed adenovirus vector vaccines expressing PCV2 Cap
      either modified with Intron A and WPRE, or CD40L and GMCSF, and evaluated all of
      these vaccines in mice and in pigs. Although Ad-A-C-W and Ad-CD40L-Cap-GMCSF
      could induce stronger immune responses than Ad-Cap, neither of them was better
      than commercial inactivated vaccine PCV2 SH-strain. In this study, secretory
      recombinant adenoviruses (Ad-A-spCap-W and Ad-A-spCD40L-spCap-spGMCSF-W) and non
      secretory recombinant adenovirus Ad-A-CD40L-Cap-GMCSF-W were constructed, and
      identified by western blot and confocal laser microscope observation. The results
      of ELISA and VN showed that humoral immune responses induced by Ad-A-spCap-W and
      Ad-A-CD40L-Cap-GMCSF-W were not significantly different from SH-strain, but Ad-A
      spCD40L-spCap-spGMCSF-W could induce significantly higher humoral immune response
      than SH-strain. Lymphocytes proliferative and cytokines releasing levels of Ad-A
      spCap-W and Ad-A-CD40L-Cap-GMCSF-W were not significantly different from SH
      strain, but Ad-A-spCD40L-spCap-spGMCSF-W was significantly higher than SH-strain.
      PCV2-challenge experiment showed that virus loads were significantly reduced in
      Ad-A-spCD40L-spCap-spGMCSF-W vaccinated group, and no obviously clinical and
      microscopic lesions were observed in Ad-A-spCD40L-spCap-spGMCSF-W vaccinated
      group. Altogether, these results demonstrate that recombinant adenovirus vaccine
      Ad-A-spCD40L-spCap-spGMCSF-W induces stronger immune responses and provides
      better protection than commercial inactivated vaccine PCV2 SH-strain, and suggest
      that Ad-A-spCD40L-spCap-spGMCSF-W could be a potential vaccine candidate against
      PCVAD.

PMID- 28755835
TI  - The value of multi-country joint regulatory reviews: The experience of a WHO
      joint technical consultation on the CYD-TDV (Dengvaxia(r)) dossier.

PMID- 28755836
TI  - Influenza seasonality goes south in the Yucatan Peninsula: The case for a
      different influenza vaccine calendar in this Mexican region.
AB  - INTRODUCTION: While vaccination may be relatively straightforward for regions
      with a well-defined winter season, the situation is quite different for tropical
      regions. Influenza activity in tropical regions might be out of phase with the
      dynamics predicted for their hemispheric group thereby impacting the
      effectiveness of the immunization campaign. OBJECTIVE: To investigate how the
      climatic diversity of Mexico hinders its existing influenza immunization strategy
      and to suggest that the hemispheric vaccine recommendations be tailored to the
      regional level in order to optimize vaccine effectiveness. METHODS: We studied
      the seasonality of influenza throughoutMexico by modeling virological and
      mortality data.De-trended time series of each Mexican state were analyzed by
      Fourier decomposition to describe the amplitude and timing of annual influenza
      epidemic cycles and to compare with each the timing of the WHO's Northern and
      Southern Hemispheric vaccination schedule. FINDINGS: The timings of the primary
      (major) peaks of both virological and mortality data for most Mexican states are
      well aligned with the Northern Hemisphere winter (December-February) and vaccine
      schedule. However, influenza peaks in September in the three states of the
      Yucatan Peninsula. Influenza-related mortality also peaks in September in
      Quintana Roo and Yucatan whereas it peaks in May in Campeche. As the current
      timing of vaccination in Mexico is between October and November, more than half
      of the annual influenza cases have already occurred in the Yucatan Peninsula
      states by the time the Northern Hemispheric vaccine is delivered and
      administered. CONCLUSION: The current Northern Hemispheric influenza calendar
      adopted for Mexico is not optimal for the Yucatan Peninsula states thereby likely
      reducing the effectiveness of the immunization of the population. We recommend
      that Mexico tailor its immunization strategy to better reflect its climatologic
      and epidemiological diversity and adopt the WHO Southern Hemisphere influenza
      vaccine and schedule for the Yucatan Peninsula.

PMID- 28755837
TI  - Missed opportunities for catch-up human papillomavirus vaccination among
      university undergraduates: Identifying health decision-making behaviors and
      uptake barriers.
AB  - BACKGROUND: Suboptimal adolescent human papillomavirus (HPV) vaccine rates in the
      US highlight the need for catch-up vaccination. When teenagers enter college,
      there may be a shift in healthcare decision-making from parents and guardians to
      the students themselves. Little is known about factors influencing college
      students' healthcare decision-making processes. STUDY DESIGN: We evaluated HPV
      vaccine decision-making among 18-to-26-year-old college students through a self
      administered, anonymous, cross-sectional survey. This survey was distributed to a
      sample of men and women in classroom settings at two universities. Categorical
      data comparisons were conducted using Chi-square and Fisher's exact tests.
      Multivariate Poisson regression was used to model initiation of HPV vaccine and
      compute prevalence ratios while controlling for key influential covariates at the
      0.05 alpha level. RESULTS: A total of 527 students participated (response
      proportion=93.1%). Overall, 55.8% of participants received the HPV vaccine.
      Encouraging conversations with doctors and/or parents/guardians were identified
      as one of the most influential factors to increase vaccine uptake. Among students
      who received encouragement from both a doctor and parent, 95.8% received the
      vaccine. Campaigns about cancer prevention were viewed as more influential than
      those that focus on preventing genital warts. Approximately one-third of students
      indicated they didn't know where to get the HPV vaccine. Women were more likely
      to report that their parents would not let them get the HPV vaccine compared to
      men (26.7% vs. 2.3%). The majority of students (77.3%) indicated their parents
      were sometimes, equally, or mostly involved in making decisions about receiving
      vaccines (other than flu). CONCLUSION: Students' decision-making is greatly
      influenced by their parents; therefore, interventions for this population should
      work to increase students' control over decision-making while also addressing
      parental concerns.

PMID- 28755838
TI  - Hematopoietic stem cell transplantation in Pakistan - country report.

PMID- 28755840
TI  - Experimental maternal treatment with dexamethasone during lactation induces
      neonatal testicular and epididymal oxidative stress; Implications for early
      postnatal exposure.
AB  - Maternal treatment with dexamethasone during lactation alters reproductive
      functions and increases serum corticosterone in the male offspring. Excess
      corticosterone may induce oxidative stress. This study was designed to evaluate
      the effects of maternal treatment with dexamethasone during lactation on
      oxidative stress indices in the testis and epididymis of a male offspring. Twenty
      lactating dams were divided into 4 groups (n=5). Group 1 was administered
      0.02ml/100g/day normal saline subcutaneously at lactation days 1-21. Groups 2, 3,
      and 4 were administered 100MUg/kg/day dexamethasone (Dex) subcutaneously at
      lactation days (LD) 1-7, 1-14, and 1-21 respectively. Testis and epididymis
      malondialdehyde (MDA), catalase and superoxide dismutase (SOD) activities were
      measured as markers of oxidative stress. The mean testis and epididymis MDA were
      significantly raised (p<0.05) in the dexamethasone-treated groups when compared
      with control. This was accompanied with a significant reduction (p<0.05) in SOD
      and catalase activities in these tissues in the DexLD 1-21, when compared with
      control. The mean total protein level of the epididymis was significantly reduced
      (p<0.05) in all the dexamethasone treated groups when compared with control. In
      conclusion, maternal treatment with dexamethasone during the first two weeks of
      lactation and throughout lactation may lead to increase in oxidative stress in
      the testis and epididymis of the male offspring of Wistar rats.

PMID- 28755839
TI  - Peripheral complement interactions with amyloid beta peptide in Alzheimer's
      disease: 2. Relationship to amyloid beta immunotherapy.
AB  - INTRODUCTION: Our previous studies have shown that amyloid beta peptide (Abeta)
      is subject to complement-mediated clearance from the peripheral circulation, and
      that this mechanism is deficient in Alzheimer's disease. The mechanism should be
      enhanced by Abeta antibodies that form immune complexes (ICs) with Abeta, and
      therefore may be relevant to current Abeta immunotherapy approaches. METHODS:
      Multidisciplinary methods were employed to demonstrate enhanced complement
      mediated capture of Abeta antibody immune complexes compared with Abeta alone in
      both erythrocytes and THP1-derived macrophages. RESULTS: Abeta antibodies
      dramatically increased complement activation and opsonization of Abeta, followed
      by commensurately enhanced Abeta capture by human erythrocytes and macrophages.
      These in vitro findings were consistent with enhanced peripheral clearance of
      intravenously administered Abeta antibody immune complexes in nonhuman primates.
      DISCUSSION: Together with our previous results, showing significant Alzheimer's
      disease deficits in peripheral Abeta clearance, the present findings strongly
      suggest that peripheral mechanisms should not be ignored as contributors to the
      effects of Abeta immunotherapy.

PMID- 28755841
TI  - Gene expression profiles in whole blood and associations with metabolic
      dysregulation in obesity.
AB  - BACKGROUND: Gene expression data provides one tool to gain further insight into
      the complex biological interactions linking obesity and metabolic disease. This
      study examined associations between blood gene expression profiles and metabolic
      disease in obesity. METHODS: Whole blood gene expression profiles, performed
      using the Illumina HT-12v4 Human Expression Beadchip, were compared between (i)
      individuals with obesity (O) or lean (L) individuals (n=21 each), (ii)
      individuals with (M) or without (H) Metabolic Syndrome (n=11 each) matched on age
      and gender. Enrichment of differentially expressed genes (DEG) into biological
      pathways was assessed using Ingenuity Pathway Analysis. Association between sets
      of genes from biological pathways considered functionally relevant and Metabolic
      Syndrome were further assessed using an area under the curve (AUC) and cross
      validated classification rate (CR). RESULTS: For OvL, only 50 genes were
      significantly differentially expressed based on the selected differential
      expression threshold (1.2-fold, p<0.05). For MvH, 582 genes were significantly
      differentially expressed (1.2-fold, p<0.05) and pathway analysis revealed
      enrichment of DEG into a diverse set of pathways including immune/inflammatory
      control, insulin signalling and mitochondrial function pathways. Gene sets from
      the mTOR signalling pathways demonstrated the strongest association with
      Metabolic Syndrome (p=8.1*10-8; AUC: 0.909, CR: 72.7%). CONCLUSIONS: These
      results support the use of expression profiling in whole blood in the absence of
      more specific tissue types for investigations of metabolic disease. Using a
      pathway analysis approach it was possible to identify an enrichment of DEG into
      biological pathways that could be targeted for in vitro follow-up.

PMID- 28755842
TI  - High serum ferritin levels are associated with insulin resistance but not with
      impaired glucose tolerance in a healthy people population.
AB  - AIM: To assess the association between elevated serum ferritin levels and the
      presence of insulin resistance (IR) or impaired glucose tolerance (IGT) in a
      population of individuals with no endocrine or metabolic disorders background.
      METHODS: Analytical cross-sectional study, carried out in adults of both sexes
      with no medical history of type 2 diabetes mellitus (T2DM) or other metabolic or
      endocrine disorder, who attended the outpatient service of a private clinic in
      Lima-Peru during 2012-2014 period. Impaired serum ferritin levels were defined as
      serum ferritin values >300MUg/L in men and >200MUg/L in women. IR was defined as
      a Homeostasis Model Assessment (HOMA-IR) value >=3.8 and IGT was defined as an
      oral glucose tolerance test (OGTT) value between 126mg/dL and 199mg/dL. The
      reported association measure was the prevalence ratio (PR) with their respective
      95% confidence intervals (95% CI). RESULTS: We analyzed 213 participants, the
      average age was 35.8+/-11.1years and 35.7% were males. The prevalence of impaired
      serum ferritin levels, IR and IGT in the population was 12.7%, 33.3% and 9.9%
      respectively. In the adjusted Poisson regression models, the prevalence of IR was
      higher among the group with impaired serum ferritin levels (PR=1.74; 95%CI:1.18
      2.56); however, we found no association between impaired serum ferritin levels
      and IGT (PR=1.42; 95%CI:0.47-4.30). CONCLUSIONS: Impaired levels of serum
      ferritin are associated with IR, nevertheless, not with IGT in a metabolically
      healthy population. Serum ferritin could be considered as an early marker of IR
      prior to the onset of glycaemia disorders.

PMID- 28755843
TI  - Serum level of orexin-A, leptin, adiponectin and insulin in north Indian obese
      women.
AB  - BACKGROUND AND AIMS: Obesity is regulated by different metabolic factors like
      leptin, adiponectin insulin and neuropeptide orexin-A. The aim of this study is
      to assess the role of these hormones and their interrelationship with obesity in
      north Indian women. METHOD: A total of 168 obese women with Body Mass Index
      (BMI)>30kg/m2 and 150 lean women (BMI<25kg/m2) as control were recruited in this
      study. Women with obesity were further subdivided into two groups according to
      their BMI, 71 overweight women with the BMI 25-29.9kg/m2 (mean+/-S.D: 27.87+/
      0.71) and the 97 obese women with BMI>30kg/m2 (34.68+/-1.90). Orexin -A, leptin
      and adiponectin were estimated using quantitative sandwich enzyme linked
      immunoassay and insulin was estimated by using an immuno-radiometric assay.
      RESULT: Orexin -A and adiponectin level were significantly lower however, leptin
      and inulin level were significantly higher in obese women as compared with
      control group. Further, the one- way group analysis showed that the orexin -A and
      adiponectin level were significantly lower but leptin and insulin level was
      significantly higher in obese women as compared to overweight and control group
      respectively. CONCLUSION: Result showed that the level of adiponectin, leptin,
      orexin-A and insulin play an important role in the regulation of energy
      expenditure. In obesity, the activity of these peptides is disturbed.

PMID- 28755844
TI  - Investigating the relationship between quality of life with lipid and glucose
      levels in Iranian diabetic patients.
AB  - BACKGROUND: Metabolic disorders including obesity, diabetes and hyperlipidemia
      are the most important human health problems. AIMS: This study aimed to determine
      the relationship between quality of life (QOL) with lipid and glucose levels in
      diabetic patients of Hamadan, Iran in 2016. METHODS: This was a cross-sectional
      study. The research sample consisted of 112 patients with type II diabetes (56
      men and 56 women) who were referred to the public hospitals and diabetes research
      center in Hamadan, Iran. The samples were selected randomly from the list
      patients. Data were collected using a questionnaire that consisting of three
      parts: demographic characteristics, quality of life and the laboratory results of
      Fasting Blood Sugar (FBS), blood lipid profiles and HbA1c. Data were analyzed
      using SPSS 20 software. RESULTS: The average age of men was 12/4+/-57/8years and
      the average age of women was 15/2+/-55/1years. This study showed that the QOL in
      53.6% of people was undesirable and 46.4% were desirable. HbA1c level was
      significantly higher in men than women. Whereas, HDL levels were significantly
      higher in women than men (p>0/05). There was no significant correlation between
      blood lipids, FBS and quality of life of patients. The individual characteristics
      such as education, economic status and duration of diabetes had significant
      correlation with quality of life (p<0.05). CONCLUSION: Due to the unsatisfactory
      quality of life in diabetes patients, it is recommended that implementation of
      training programs for diabetes patients and application suitable care approaches
      to enhance diabetes QOL.

PMID- 28755845
TI  - Marketing masked as clinical research. The Phase IIIB studies and other sample
      cases.

PMID- 28755846
TI  - Irisin - A potential contributor of insulin resistance in kidney failure.

PMID- 28755847
TI  - Prospective study of metabolic syndrome as a mortality marker in chronic coronary
      heart disease patients.
AB  - BACKGROUND: We aimed to clarify the impact of metabolic syndrome (MetS) as
      assessed by different definitions on the cardiovascular mortality in patients
      with coronary heart disease (CHD). METHODS: A total of 1692 patients, 6-24months
      after myocardial infarction and/or coronary revascularization at baseline, were
      followed in a prospective cohort study. MetS was identified using four different
      definitions: standard National Cholesterol Education Program definition (NCEP
      ATPIII) based on the presence of >=3 of the following factors: increased waist
      circumference, raised blood pressure, hypetriglyceridemia, low high-density
      lipoprotein cholesterol, and increased fasting glycemia; modified NCEP-ATPIII
      definition (similar, but omitting antihypertensive treatment as an alternative
      criterion); presence of "atherogenic dyslipidemia"; or "hypertriglyceridemic
      waist". The primary outcome was a fatal cardiovascular event at 5years. RESULTS:
      During 5-year follow-up, 117 patients (6.9%) died from a cardiovascular cause.
      Patients with MetS by modified NCEP-ATPIII (n=1066, 63.0% of the whole sample)
      had significantly higher 5-year cardiovascular mortality [adjusted hazard risk
      ratio (HRR) 2.01 [95%CI:1.26-3.22]; p=0.003] than subjects without MetS. However,
      when testing single MetS component factors, the majority of attributable
      mortality risk was driven by increased fasting glycemia (>=5.6mmol/L) [HRR 2.69
      (95%CI:1.29-5.62), p=0.009] and the significance of MetS disappeared. None of the
      other MetS definitions, i.e., standard NCEP-ATPIII (n=1210; 71.5%),
      "hypertriglyceridemic waist" (n=455; 26.9%) or "atherogenic dyslipidemia" (n=223;
      13.2%) were associated with any significant mortality risk. CONCLUSIONS: The co
      incidence of MetS has a limited mortality impact in CHD patients, while an
      increase in fasting glycemia seems to be more a specific marker of mortality
      risk.

PMID- 28755848
TI  - The use of Brazilian propolis for discovery and development of novel anti
      inflammatory drugs.
AB  - Anti-Inflammatory drugs have been routinely used in the management of acute and
      chronic inflammatory conditions. Nevertheless, their undesirable side and adverse
      effects have encouraged the development of more selective, tolerable and
      efficacious drugs able to modulate the inflammatory process through distinct
      mechanisms than those of drugs currently available in the market, for instance,
      inhibition of leukocyte recruitment (chemotaxis, rolling, adhesion and
      transmigration). Natural products, including Brazilian propolis, have been
      considered a rich source of anti-inflammatory molecules due to a very complex
      phytochemical diversity. Brazil has at least thirteen distinct types of propolis
      and many bioactive compounds have been isolated therefrom, such as apigenin,
      artepillin C, vestitol, neovestitol, among others. These molecules were proven to
      play a significant immunomodulatory role through (i) inhibition of inflammatory
      cytokines (e.g. TNF-alpha) and chemokines (CXCL1/KC and CXCL2/MIP2); (ii)
      inhibition of IkappaBalpha, ERK1/2, JNK and p38MAPK phosphorylation; (iii)
      inhibition of NF-kappaB activation; and (iv) inhibition of neutrophil adhesion
      and transmigration (ICAM-1, VCAM-1 and E-selectin expression). In this review, we
      shed light on the new advances in the research of compounds isolated from
      Brazilian propolis from Apis mellifera bees as potentially novel anti
      inflammatory drugs. The compilation of data and insights presented herein may
      open further avenues for the pharmacological management of oral and systemic
      inflammatory conditions. Further research should focus on clinical and
      acute/chronic toxicological validation of the most promising compounds described
      in this review.

PMID- 28755849
TI  - Current antiviral drugs and their analysis in biological materials-Part I:
      Antivirals against respiratory and herpes viruses.
AB  - This review article is the first in the series providing an overview of currently
      used antiviral drugs and presenting contemporary approaches to their analysis.
      Large number of available antivirals and their structural variability makes this
      task very challenging. Trying to cover this topic comprehensively while
      maintaining reasonable size of the article, the review is presented in two parts.
      For the purpose of the overall review, antivirals were divided into four groups:
      (i) antivirals against herpes viruses, (ii) antivirals against respiratory
      viruses, (iii) antivirals against hepatitis viruses, and (iv) antivirals against
      HIV. Part one is devoted to the groups (i) and (ii) and also concerns the key
      features of the bioanalytical method. The mechanisms of action of antivirals
      against respiratory and herpes viruses and their use in clinical practice are
      briefly outlined, and the analytical methods for selected representatives of each
      class are described in more detail. The methods developed for the determination
      of drugs from these classes mostly include conventional procedures. In contrast,
      current trends such as UHPLC are used rarely and proper method validation based
      on requirements of bioanalytical guidelines can be often considered insufficient.

PMID- 28755850
TI  - SIPS as a model to study age-related changes in proteolysis and aggregate
      formation.
AB  - Aging is accompanied by the accumulation of cellular damage over time in response
      to stress, lifestyle and environmental factors ultimately leading to age-related
      diseases and death. Additionally, the number of senescent cells increases with
      age. Senescence is most likely not a static endpoint, it represents a series of
      hallmarks including morphological changes, alterations in protein turnover and
      accumulation of protein aggregates. The importance of protein oxidation and
      aggregate accumulation in the progression of aging is not yet fully understood
      and research to what extent the accumulation of oxidized proteins has an effect
      on senescence and the aging process is still ongoing. To study the mechanisms of
      aging, the impact of senescence and the role of protein aggregates on the aging
      process, cell culture models are useful tools. Most notably stress induced
      premature senescence (SIPS) models have contributed to the identification of
      mechanisms involved in the aging process and helped unravel the age-related
      changes in proteolysis and the importance of protein aggregation. Here we review
      characteristics of replicative and premature senescence, how to induce most
      frequently used senescence models and gained knowledge on age-related changes in
      the major proteolytic systems.

PMID- 28755851
TI  - Application of a flexible lightwand during percutaneous dilatational tracheotomy.

PMID- 28755852
TI  - Noxious newts and their natural enemies: Experimental effects of tetrodotoxin
      exposure on trematode parasites and aquatic macroinvertebrates.
AB  - The dermal glands of many amphibian species secrete toxins or other noxious
      substances as a defense strategy against natural enemies. Newts in particular
      possess the potent neurotoxin tetrodotoxin (TTX), for which the highest
      concentrations are found in species within the genus Taricha. Adult Taricha are
      hypothesized to use TTX as a chemical defense against vertebrate predators such
      as garter snakes (Thamnophis spp.). However, less is known about how TTX
      functions to defend aquatic-developing newt larvae against natural enemies,
      including trematode parasites and aquatic macroinvertebrates. Here we
      experimentally investigated the effects of exogenous TTX exposure on survivorship
      of the infectious stages (cercariae) of five species of trematode parasites that
      infect larval amphibians. Specifically, we used dose-response curves to test the
      sensitivity of trematode cercariae to progressively increasing concentrations of
      TTX (0.0 [control], 0.63, 3.13, 6.26, 31.32, and 62.64 nmol L-1) and how this
      differed among parasite species. We further compared these results to the effects
      of TTX exposure (0 and 1000 nmolL-1) over 24 h on seven macroinvertebrate taxa
      commonly found in aquatic habitats with newt larvae. TTX significantly reduced
      the survivorship of trematode cercariae for all species, but the magnitude of
      such effects varied among species. Ribeiroia ondatrae - which causes mortality
      and limb malformations in amphibians - was the least sensitive to TTX, whereas
      the kidney-encysting Echinostoma trivolvis was the most sensitive. Among the
      macroinvertebrate taxa, only mayflies (Ephemeroptera) showed a significant
      increase in mortality following exogenous TTX exposure, despite the use of a
      concentration 16x higher than the maximum used for trematodes. Our results
      suggest that maternal investment of TTX into larval newts may provide protection
      against certain trematode infections and highlight the importance of future work
      assessing the effects of newt toxicity on both parasite infection success and the
      palatability of larval newts to invertebrate predators.

PMID- 28755854
TI  - Lowering Size Threshold for Elective Repair to Reduce Deaths from Abdominal
      Aortic Aneurysms - A Simple Solution to a Complex Problem?

PMID- 28755853
TI  - Search and recovery of autobiographical and laboratory memories: Shared and
      distinct neural components.
AB  - Functional neuroimaging evidence suggests that there are differences in the
      neural correlates of episodic memory for laboratory stimuli (laboratory memory)
      and for events from one's own life (autobiographical memory). However, this
      evidence is scarce and often confounded with differences in memory testing
      procedures. Here, we directly compared the neural mechanisms underlying the
      search and recovery of autobiographical and laboratory memories while minimizing
      testing differences. Before scanning, participants completed a laboratory memory
      encoding task in which they studied four-word "chains" spread across three word
      pairs. During scanning, participants completed a laboratory memory retrieval
      task, in which they recalled the word chains, and an autobiographical memory
      retrieval task, in which they recalled specific personal events associated with
      word cues. Importantly, response times were similar in the two tasks, allowing
      for a direct comparison of the activation time courses. We found that during
      memory search (searching for the memory target), similar brain regions were
      activated during both the autobiographical and laboratory tasks, whereas during
      memory recovery (accessing the memory traces; i.e., ecphory), clear differences
      emerged: regions of the default mode network (DMN) were activated greater during
      autobiographical than laboratory memory, whereas the bilateral superior parietal
      lobules were activated greater during laboratory than autobiographical memory.
      Also, multivariate functional connectivity analyses revealed that regardless of
      memory stage, the DMN and ventral attention network exhibited a more integrated
      topology in the functional network underlying autobiographical (vs. laboratory)
      memory retrieval, whereas the fronto-parietal task control network exhibited a
      more integrated topology in the functional network underlying laboratory (vs.
      autobiographical) memory retrieval. These findings further characterize the
      shared and distinct neural components underlying autobiographical and laboratory
      memories, and suggest that differences in autobiographical vs. laboratory memory
      brain activation previously reported in the literature reflect memory recovery
      rather than search differences.

PMID- 28755855
TI  - Editor's Choice - Very Urgent Carotid Endarterectomy is Associated with an
      Increased Procedural Risk: The Carotid Alarm Study.
AB  - OBJECTIVE/BACKGROUND: The aim of the Carotid Alarm Study was to compare the
      procedural risk of carotid endarterectomy (CEA) performed within 48 hours with
      that after 48 hours to 14 days following an ipsilateral cerebrovascular ischaemic
      event. METHODS: Consecutive patients with symptomatic carotid stenosis undergoing
      CEA were prospectively recruited. Time to surgery was calculated as time from the
      most recent ischaemic event preceding surgery. A neurologist examined patients
      before and, after CEA. The primary endpoint was the composite endpoint of death
      and/or any stroke within 30 days of the surgical procedure. The study was
      designed to include 600 patients, with 150 operated on within 48 hours. RESULTS:
      From October 2010 to December 2015, 418 patients were included, of whom 75 were
      operated within 48 hours of an ischaemic event. The study was prematurely
      terminated owing to the slow recruitment rate in the group operated on within 48
      hours. Patients undergoing CEA within 48 hours had a higher risk of reaching the
      primary endpoint than those operated on later (8.0% vs. 2.9%). Multivariate
      logistic regression analyses showed that CEA performed within 48 h (odds ratio
      [OR] 3.07; 95% confidence interval [CI] 1.04-9.09), CEA performed out of office
      hours (OR 3.65; 95% CI 1.14-11.67), and use of shunt (OR 4.02; 95% CI 1.36-11.93)
      were all independently associated with an increased risk of reaching the primary
      endpoint. CONCLUSION: CEA performed within 48 hours was associated with a higher
      risk of complications compared with surgery performed 48 hours-14 days after the
      most recent ischaemic event.

PMID- 28755856
TI  - Th9 cells induce steroid-resistant bronchial hyperresponsiveness in mice.
AB  - BACKGROUND: Reduced responsiveness to corticosteroid therapy is a major problem
      for patients with severe asthma. Although Th9 cells, along with Th2 cells,
      facilitate antigen-induced airway eosinophilia and bronchial hyperresponsiveness
      (BHR), the sensitivity of Th9 cell-mediated responses to steroid therapy remains
      unknown. In this study, we investigated the effect of dexamethasone (Dex) on
      antigen-induced airway inflammation in Th9 cell-transferred mice. METHODS:
      Ovalbumin (OVA)-specific Th2 and Th9 cells were polarized from the CD4+ T cells
      of DO11.10/RAG-2-/- mice. BALB/c mice were adoptively transferred with Th2 or Th9
      cells and challenged with OVA. Dex treatment was performed twice, at 1 h before
      and at 24 h after the OVA challenge. Following treatment, the number of
      inflammatory cells in the bronchoalveolar lavage fluid and the bronchial
      responsiveness to inhaled methacholine were determined. RESULTS: In both the Th2
      and Th9 cell-transferred mice, substantial accumulation of eosinophils in the
      lungs and BHR were induced by challenge with the specific antigen. In the Th2
      cell-transferred mice, these responses were significantly diminished by Dex
      treatment. In contrast, neither cellular infiltration nor BHR was affected by Dex
      treatment in the Th9 cell-transferred mice, although the Th9 cells substantially
      expressed glucocorticoid receptor alpha. Accordingly, antigen-induced interleukin
      9 expression in the Th9 cells was attenuated by Dex treatment at least in vitro.
      Antigen-induced lung infiltration of infused Th2 cells but not Th9 cells was
      significantly suppressed by Dex. CONCLUSIONS: In contrast to Th2-mediated
      responses, Th9-mediated airway inflammation was not affected by Dex. Th9 cells
      might be involved in the developmental mechanisms of steroid-resistant asthma.

PMID- 28755857
TI  - Editorial Commentary: Alcohol consumption and cardiovascular health: The
      challenges of complexity.

PMID- 28755858
TI  - Iodine is associated to semen quality in men who undergo consultations for
      infertility.
AB  - The role that adequate iodine intake could have on the male reproductive function
      is not entirely known. The aim of this study is to determine whether there is a
      relation between male infertility and urinary and semen iodine levels in 96
      couples who underwent consultation for infertility. The median of semen iodine
      was higher in men who consumed iodized salt than in those who consumed non
      iodized salt (p=0.019). Men with a higher semen iodine level had more
      morphological alterations in spermatozoa (p=0.032). Men with a higher urinary
      iodine level had a lower motile sperm count according to the "direct swim-up"
      technique (p=0.044). Men >3years without successfully achieving pregnancy had a
      higher urinary iodine level than those with <= 3years (p=0.035). In conclusion,
      iodine may play a role in the quality of semen: an increase in semen iodine
      levels is associated with different variables related to male infertility.

PMID- 28755859
TI  - Systemic inflammation combined with neonatal cerebellar haemorrhage aggravates
      long-term structural and functional outcomes in a mouse model.
AB  - BACKGROUND: Despite the increased recognition of cerebellar injury in survivors
      of preterm birth, the neurodevelopmental consequences of isolated cerebellar
      injury have been largely unexplored and our current understanding of the
      functional deficits requires further attention in order to translate knowledge to
      best practices. Preterm infants are exposed to multiple stressors during their
      postnatal development including perinatal cerebellar haemorrhage (CBH) and
      postnatal infection, two major risk factors for neurodevelopmental impairments.
      METHODS: We developed a translational mouse model of CBH and/or inflammation to
      measure the short- and long-term outcomes in cerebellar structure and function.
      RESULTS: Mice exposed to early combined insults of CBH and early inflammatory
      state (EIS) have a delay in grasping acquisition, neonatal motor deficits and
      deficient long-term memory. CBH combined with late inflammatory state (LIS) does
      not induce neonatal motor problems but leads to poor fine motor function and long
      term memory deficits at adulthood. Early combined insults result in poor
      cerebellar growth from postnatal day 15 until adulthood shown by MRI, which are
      reflected in diminished volumes of cerebellar structures. There are also
      decreases in volumes of gray matter and hippocampus. Cerebellar microgliosis
      appears 24h after the combined insults and persists until postnatal day 15 in the
      cerebellar molecular layer and cerebellar nuclei in association with a disrupted
      patterning of myelin deposition, a delay of oligodendrocyte maturation and
      reduced white matter cerebellar volume. CONCLUSIONS: Together, these findings
      reveal poor outcomes in developing brains exposed to combined cerebellar
      perinatal insults in association with cerebellar hypoplasia, persistence of
      microgliosis and alterations of cerebellar white matter maturation and growth.

PMID- 28755860
TI  - Dynamic and accurate assessment of acetaminophen-induced hepatotoxicity by
      integrated photoacoustic imaging and mechanistic biomarkers in vivo.
AB  - The prediction and understanding of acetaminophen (APAP)-induced liver injury
      (APAP-ILI) and the response to therapeutic interventions is complex. This is due
      in part to sensitivity and specificity limitations of currently used assessment
      techniques. Here we sought to determine the utility of integrating translational
      non-invasive photoacoustic imaging of liver function with mechanistic circulating
      biomarkers of hepatotoxicity with histological assessment to facilitate the more
      accurate and precise characterization of APAP-ILI and the efficacy of therapeutic
      intervention. Perturbation of liver function and cellular viability was assessed
      in C57BL/6J male mice by Indocyanine green (ICG) clearance (Multispectral
      Optoacoustic Tomography (MSOT)) and by measurement of mechanistic (miR-122,
      HMGB1) and established (ALT, bilirubin) circulating biomarkers in response to the
      acetaminophen and its treatment with acetylcysteine (NAC) in vivo. We utilised a
      60% partial hepatectomy model as a situation of defined hepatic functional mass
      loss to compared acetaminophen-induced changes to. Integration of these
      mechanistic markers correlated with histological features of APAP hepatotoxicity
      in a time-dependent manner. They accurately reflected the onset and recovery from
      hepatotoxicity compared to traditional biomarkers and also reported the efficacy
      of NAC with high sensitivity. ICG clearance kinetics correlated with histological
      scores for acute liver damage for APAP (i.e. 3h timepoint; r=0.90, P<0.0001) and
      elevations in both of the mechanistic biomarkers, miR-122 (e.g. 6h timepoint;
      r=0.70, P=0.005) and HMGB1 (e.g. 6h timepoint; r=0.56, P=0.04). For the first
      time we report the utility of this non-invasive longitudinal imaging approach to
      provide direct visualisation of the liver function coupled with mechanistic
      biomarkers, in the same animal, allowing the investigation of the toxicological
      and pharmacological aspects of APAP-ILI and hepatic regeneration.

PMID- 28755861
TI  - High serum lead concentration in the first trimester is associated with an
      elevated risk of small-for-gestational-age infants.
AB  - A recent study found that gestational serum Pb concentration is associated with
      an increased risk of preterm birth. The purpose of this study was to analyze
      whether gestational Pb exposure elevates risk of small-for-gestational-age (SGA)
      births in a Chinese population. In the present study, total 3125 mother-infant
      pairs were recruited from the China-Anhui Birth Cohort Study (C-ABCS). Pb
      concentration in maternal serum was detected by GFAAS. All subjects were
      classified into three groups according to the tertile division of serum Pb
      concentration: L-Pb (low-Pb, <1.18MUg/dl), M-Pb (medium-Pb, 1.18-1.70MUg/dl), and
      H-Pb (high-Pb, >=1.71MUg/dl). There was no difference on birth length, head
      circumference and chest circumference among different groups. The rate of SGA was
      6.2% in subjects with L-Pb, 8.7% in subjects with M-Pb, and 10.1% in subjects
      with H-Pb, respectively. The adjusted OR of SGA was 1.45 (95%CI: 1.04, 2.02;
      P=0.03) in subjects with M-Pb and 1.69 (95%CI: 1.22, 2.34; P=0.002) in subjects
      with H-Pb. Interestingly, the rate of SGA infants was elevated only in subjects
      with H-Pb in the first trimester (adjusted OR: 2.13; 95%CI: 1.24, 3.38; P=0.007).
      Collectively, high serum Pb level in the first trimester is associated with an
      elevated risk of SGA infants.

PMID- 28755862
TI  - Ketamine changes the local resting-state functional properties of anesthetized
      monkey brain.
AB  - OBJECTIVE: Ketamine is a well-known anesthetic. 'Recreational' use of ketamine
      common induces psychosis-like symptoms and cognitive impairments. The acute and
      chronic effects of ketamine on relevant brain circuits have been studied, but the
      effects of single-dose ketamine administration on the local resting-state
      functional properties of the brain remain unknown. In this study, we aimed to
      assess the effects of single-dose ketamine administration on the brain local
      intrinsic properties. METHODS: We used resting-state functional magnetic
      resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain
      intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to
      examine the fractional amplitude of low-frequency fluctuation (fALFF) and
      regional homogeneity (ReHo) in the brain before and after ketamine injection.
      Paired comparisons were used to detect the significantly altered regions.
      RESULTS: Results showed that the fALFF of the prefrontal cortex (p=0.046),
      caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020)
      in post-injection stage significantly increased compared with those in pre
      injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus
      (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that
      of prefrontal cortex decreased (p<0.05). CONCLUSIONS: These findings demonstrated
      that single-dose ketamine administration can change the regional intensity and
      synchronism of brain activity, thereby providing evidence of ketamine-induced
      abnormal resting-state functional properties in primates. This evidence may help
      further elucidate the effects of ketamine on the cerebral resting status.

PMID- 28755864
TI  - ?

PMID- 28755865
TI  - ?

PMID- 28755863
TI  - Estrogenic regulation of memory consolidation: A look beyond the hippocampus,
      ovaries, and females.
AB  - The potent estrogen 17beta-estradiol (E2) has long been known to regulate the
      hippocampus and hippocampal-dependent memories in females, and research from the
      past decade has begun to shed light on the molecular mechanisms through which E2
      mediates memory formation in females. Although E2 can also regulate hippocampal
      function in males, relatively little is known about how E2 influences memory
      formation in males, or whether sex differences in underlying mechanisms exist.
      This review, based on a talk given in April 2017 at the American University
      symposium entitled, "Sex Differences: From Neuroscience to the Clinic and
      Beyond", first provides an overview of the molecular mechanisms in the dorsal
      hippocampus through which E2 enhances memory consolidation in ovariectomized
      female mice. Next, newer research is described demonstrating key roles for the
      prefrontal cortex and de novo hippocampal E2 synthesis to the memory-enhancing
      effects of E2 in females. The review then discusses the effects of de novo and
      exogenous E2 on hippocampal memory consolidation in both sexes, and putative sex
      differences in the underlying molecular mechanisms through which E2 enhances
      memory formation. The review concludes by discussing the importance and
      implications of sex differences in the molecular mechanisms underlying E2-induced
      memory consolidation for human health.

PMID- 28755866
TI  - Topographic and chemical surface modifications to metal brackets after a period
      in the mouth.
AB  - INTRODUCTION: In the current state of our knowledge, the effects of corrosion on
      the performance of orthodontic appliances and on patient health are far from
      clear. Awareness of these problems has led to a growing demand for nickel-free
      products. Titanium brackets were recently launched on the market as an
      alternative to stainless-steel brackets. However, the use of fluorides for caries
      prevention creates a risk of corrosion of these titanium appliances. The aim of
      this study is to examine the corrosion of stainless-steel and titanium brackets
      in clinical orthodontic use, focusing on the impact of fluorine. METHODS: After
      approval by the ethics committee and the informed consent of the patients, 30
      candidates for multi-bracket treatment were selected on the basis of certain
      exclusion criteria. The patients were divided into 4 groups: group 1: titanium
      brackets and fluorine protection; group 2: titanium brackets without fluorine
      protection; group 3: stainless-steel brackets and fluorine protection; group 4:
      stainless-steel brackets without fluorine protection. RESULTS: Analysis of the
      brackets removed after 4months in the mouth, using scanning electron microscopy
      (SEM) with phase contrast, revealed a difference in the surface topography of the
      metal brackets and the presence of chromium coating on the surface of the
      titanium appliances.

PMID- 28755867
TI  - Shear bond strength of two 2-step etch-and-rinse adhesives when bonding ceramic
      brackets to bovine enamel.
AB  - AIM: The present study assessed a fracture analysis and compared the shear bond
      strength (SBS) of two 2-step etch-and-rinse (E&R) adhesives when bonding ceramic
      orthodontic brackets to bovine enamel. MATERIALS AND METHODS: Thirty healthy
      bovine mandibular incisors were selected and were equally and randomly assigned
      to 2 experimental groups. Ceramic brackets (FLI Signature Clear(r), RMO) were
      bonded onto bovine enamel using an adhesive system. In group 1 (n=15), the
      conventional E&R adhesive (OrthoSolo(r)+Enlight(r), Ormco) was used, and in group
      2 (n=15), the new E&R adhesive limited to ceramic bracket bonding (FLI ceramic
      adhesive(r): FLI sealant resin(r)+FLI adhesive paste(r), RMO) was used. In order
      to obtain appropriate enamel surfaces, the vestibular surfaces of mandibular
      bovine incisors were flat ground. After bonding, all the samples were stored in
      distilled water at room temperature for 21 days and subsequently tested for SBS,
      using the Instron(r) universal testing machine. The Adhesive Remnant Index (ARI)
      scores were evaluated. Failure modes were assessed using optical microscopy at
      magnification *40. A statistic data analysis was performed using the Mann-Whitney
      U-test (P<0.05). RESULTS: The test showed a significant difference (P=0.00155)
      between the two groups for the SBS values. Group 1 had significantly higher SBS
      values (9.79 to 20.83MPa) than group 2 (8.45 to 13.94MPa). Analysis of the ARI
      scores revealed that most of the failures occurred at the enamel/adhesive
      interface. A statistically significant difference was found for the ARI scores
      between the two groups (P=0.00996). Only two fractured brackets, which remained
      bonded onto the bovine enamel, were reported. Both occurred in group 1.
      CONCLUSION: When bonded to ceramic brackets, FLI ceramic adhesive(r) (RMO) was
      demonstrated to be very predictable and safe for clinical application in enamel
      bonding, whereas the results obtained with the conventional adhesive system
      (OrthoSolo(r)+Enlight(r), Ormco) were less reproducible and revealed slightly
      excessive shear bond strength values.

PMID- 28755868
TI  - Assessment of left ventricular function in healthy Great Danes and in Great Danes
      with dilated cardiomyopathy using speckle tracking echocardiography.
AB  - OBJECTIVES: Assess global circumferential and radial systolic and diastolic
      myocardial function with speckle tracking echocardiography (STE) in healthy Great
      Danes (GD) and in GD diagnosed with dilated cardiomyopathy (DCM). ANIMALS: Eighty
      nine GD were included in the study: 39 healthy (normal group [NORMg]) and 50
      diagnosed with DCM (DCMg). METHODS: This was a retrospective study. Signalment
      and echocardiographic diagnosis were obtained from the medical records of GD
      assessed between 2008 and 2012. Speckle tracking echocardiography analysis of
      circumferential (C) and radial (R) strain (St) and strain rate (SR) in systole
      (S), early (E) and late (A) diastole was performed at the levels of the mitral
      valve (MV), papillary muscles (PM) and apex (Ap) of the left ventricle.
      Univariable and multivariable analysis was performed to identify differences
      between groups. RESULTS: Speckle tracking echocardiography variables increase
      from the MV towards the Ap of the left ventricle in both NORMg and DCMg dogs,
      some reaching statistical significance. Most of the variables (28/31) were lower
      in DCMg than in NORMg dogs: statistically significant variables included radial
      SR at the Ap in systole (p=0.029), radial strain at the PM (p=0.012),
      circumferential SR at the PM in systole (p=0.031), circumferential and radial SR
      at the MV in early diastole (p=0.019 and p=0.049, respectively). CONCLUSIONS:
      There are significant differences in STE variables between NORMg and DCMg Great
      Danes, although the overlap between the two groups may indicate that these
      variables are not sufficiently discriminatory. STE variables are not sufficiently
      sensitive to use in isolation as a screening method.

PMID- 28755870
TI  - Use of near-infrared spectroscopy in the investigation of brain activation during
      cognitive aging: A systematic review of an emerging area of research.
AB  - The cognitive neuroscience of aging is a growing and stimulating research area.
      The development of neuroimaging techniques in the past two decades has
      considerably increased our understanding of the brain mechanisms that might
      underlie cognitive performance and resulting changes due to normal aging. Beside
      traditional metabolic neuroimaging techniques, such as Positron Emission
      Tomography and functional Magnetic Resonance Imaging, near infrared spectroscopy
      (NIRS), an optical imaging technique allowing to monitor real-time cerebral blood
      oxygenation, has gained recent interest in this field. The aim of the present
      review paper, after briefly presenting the NIRS technique, is to review and to
      summarize the recent results of neuroimaging studies using this technique in the
      field of cognitive aging. The reviewed literature shows that, despite low spatial
      resolution and cerebral depth penetration, this technique provides consistent
      findings on the reduced hemodynamic activity as a function of chronological age,
      mainly in the prefrontal cortex. Important moderators of brain hemodynamics, such
      as cognitive load, subjects' characteristics and experimental conditions, for
      which the NIRS technique is sensitive, are discussed. Strengths and weaknesses of
      functional NIRS in the field of cognitive aging are presented and finally, novel
      perspectives of research are proposed.

PMID- 28755869
TI  - Maternal exposure to childhood maltreatment and risk of stillbirth.
AB  - PURPOSE: To determine the association between maternal exposure to childhood
      maltreatment (CM) and risk of stillbirth (fetal death at or after 20 weeks'
      gestation). METHODS: Population-based case-control study from the Stillbirth
      Collaborative Research Network (SCRN) conducted in 2006-2008, and the follow-up
      study, SCRN-Outcomes after Study Index Stillbirth (SCRN-OASIS), conducted in 2009
      in the United States. Cases (n = 133) included women who experienced a
      stillbirth, excluding stillbirths attributed to genetic/structural or umbilical
      cord abnormalities and intrapartum stillbirths. Controls (n = 500) included women
      delivering a healthy term live birth (excluding births less than 37 weeks
      gestation, neonatal intensive care unit admission, or death). CM exposure was
      measured using the Childhood Trauma Questionnaire, administered during the SCRN
      OASIS study. Dichotomized scores for five subscales of CM (physical abuse,
      physical neglect, emotional abuse, emotional neglect, and sexual abuse) and an
      overall measure of CM exposure were analyzed using logistic regression. RESULTS:
      Generally, there was no association between CM and stillbirth, except for the
      emotional neglect subscale (OR: 1.93; 95% CI: 1.17, 3.19). CONCLUSIONS: Childhood
      neglect is understudied in comparison to abuse and should be included in the
      future studies of associations between CM and pregnancy outcomes, including
      stillbirth.

PMID- 28755871
TI  - Cyclohexene-fused 1,3-oxazines with selective antibacterial and antiparasitic
      action and low cytotoxic effects.
AB  - Oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of
      biological properties, such as anticonvulsant and antitumor activities. In this
      study, we evaluated the effect of two cyclohexene-fused 1,3-oxazines (cis-1
      benzyl-N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and trans-N
      phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of
      Bacillus cereus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae,
      Salmonella enterica, Serratia marcescens, Shigella flexneri and Staphylococcus
      aureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal
      Concentration (MBC). Additionally, the ex vivo antiparasitic activity of oxazines
      was assessed against Schistosoma mansoni, a helminth that is one of the major
      agents of the disease schistosomiasis Also, oxazines were evaluated on three
      tumor cell lines, NCI-H292 (human lung carcinoma), MCF-7 (human breast
      adenocarcinoma) and HEp-2 (human cervix carcinoma), and two normal cell lines
      (Vero and red blood cells). Bioassays revealed that oxazine 2 is more effective
      against bacteria than oxazine 1, with the lowest MIC and MBC values of 3.91 and
      32.5MUg/mL, respectively. Similarly, compound 2 demonstrated higher antiparasitic
      activity than 1, and scanning electron microscopy analysis showed several
      morphological alterations in the tegument of worms in a concentration-dependent
      manner. In contrast, both oxazines exhibited low cytotoxic effects on cancer and
      normal cell lines. These results indicated that oxazines exerted direct effects
      on bacteria and parasite schistosomes. More importantly, since schistosomiasis
      control programs rely on one drug, praziquantel, oxazines may have the potential
      to become new antischistosomal agents.

PMID- 28755872
TI  - New approaches for the enhancement of chimeric antigen receptors for the
      treatment of HIV.
AB  - HIV infection continues to be a life-long chronic disease in spite of the success
      of antiretroviral therapy (ART) in controlling viral replication and preventing
      disease progression. However, because of the high cost of treatment, severe side
      effects, and inefficiency in curing the disease with ART, there is a call for
      alternative therapies that will provide a functional cure for HIV. Cytotoxic T
      lymphocytes (CTLs) are vital in the control and clearance of viral infections and
      therefore immune-based therapies have attempted to engineer HIV-specific CTLs
      that would be able to clear the infection from the body. The development of
      chimeric antigen receptors (CARs) provides an opportunity to engineer superior
      HIV-specific CTLs that will be independent of the major histocompatibility
      complex for target recognition. A CD4-based CAR has been previously tested in
      clinical trials to test the antiviral efficacy of peripheral T cells armed with
      this CD4-based CAR. The results from these clinical trials showed the safety and
      feasibility of CAR T cell therapy for HIV infection; however, minimal antiviral
      efficacy was seen. In this review, we will discuss the various strategies being
      developed to enhance the therapeutic potency of anti-HIV CARs with the goal of
      generating superior antiviral responses that will lead to life-long HIV immunity
      and clearance of the virus from the body.

PMID- 28755873
TI  - Chimeric antigen receptor T-cell therapy for glioblastoma.
AB  - Chimeric antigen receptor (CAR) T-cell therapy has shown great promise in the
      treatment of hematological disease, and its utility for treatment of solid tumors
      is beginning to unfold. Glioblastoma continues to portend a grim prognosis and
      immunotherapeutic approaches are being explored as a potential treatment
      strategy. Identification of appropriate glioma-associated antigens, barriers to
      cell delivery, and presence of an immunosuppressive microenvironment are factors
      that make CAR T-cell therapy for glioblastoma particularly challenging. However,
      insights gained from preclinical studies and ongoing clinical trials indicate
      that CAR T-cell therapy will continue to evolve and likely become integrated with
      current therapeutic strategies for malignant glioma.

PMID- 28755875
TI  - Erratum.

PMID- 28755874
TI  - Antibiofilm potential of synthetic 2-amino-5-chlorobenzophenone Schiff bases and
      its confirmation through fluorescence microscopy.
AB  - Antibacterial/antibiofilm potential of microwave-assisted synthetic thirty-three
      2-amino-5-chloro benzophenone Schiff bases have been carried out against four
      bacterial strains i.e. Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus
      aureus and Streptococcus mutans. Among them compounds 5, 6, 8, 9, 14, 16, 22, 24,
      26, and 30-32 showed antibiofilm activities against isolates at less than 100
      MUg/ml concentrations. These compounds showed enhanced antibiofilm activity
      against S. aureus as compared to cefixime used as control. However, remaining
      compounds were found to be active but at higher concentration. Fluorescence
      microscopy has been employed for confirmation of antibiofilm results. The
      structures of all synthetic molecules have been characterized on the basis of
      spectroscopic techniques including 1H NMR, 13C NMR, EI-MS, HREI-MS, and IR
      spectroscopy and their structure-activity relationship have been established.

PMID- 28755876
TI  - A computational network analysis based on targets of antipsychotic agents.
AB  - Currently, numerous antipsychotic agents have been developed in the area of
      pharmacological treatment of schizophrenia. However, the molecular mechanism
      underlying multi targets of antipsychotics were yet to be explored. In this study
      we performed a computational network analysis based on targets of antipsychotic
      agents. We retrieved a total of 96 targets from 56 antipsychotic agents. By
      expression enrichment analysis, we identified that the expressions of
      antipsychotic target genes were significantly enriched in liver, brain, blood and
      corpus striatum. By protein-protein interaction (PPI) network analysis, a PPI
      network with 77 significantly interconnected target genes was generated. By
      historeceptomics analysis, significant brain region specific target-drug
      interactions were identified in targets of dopamine receptors (DRD1-Olanzapine in
      caudate nucleus and pons (P-value<0.005), DRD2-Bifeprunox in caudate nucleus and
      pituitary (P-value<0.0005), DRD4-Loxapine in Pineal (P-value<0.00001)) and 5
      hydroxytryptamine receptor (HTR2A-Risperidone in occipital lobe, prefrontal
      cortex and subthalamic nucleus (P-value<0.0001)). By pathway grouped network
      analysis, 34 significant pathways were identified and significantly grouped into
      6 sub networks related with drug metabolism, Calcium signaling, GABA receptors,
      dopamine receptors, Bile secretion and Gap junction. Our results may provide
      biological explanation for antipsychotic targets and insights for molecular
      mechanism of antipsychotic agents.

PMID- 28755877
TI  - Multiple retinal anomalies in schizophrenia.
AB  - INTRODUCTION: In addition to being a critical component of the visual system, the
      retina provides the opportunity for an accessible and noninvasive probe of brain
      pathology in neuropsychiatric disorders. Several studies have reported various
      retinal abnormalities in schizophrenia, some primary and others iatrogenic. There
      is now increasing evidence supporting the existence of retinal anomalies in
      schizophrenia across structural, neurochemical and physiological parameters.
      Here, we review the types of retinal pathology in schizophrenia and discuss how
      these findings may provide novel insights for future research into the
      neurodevelopmental neurobiology of this syndrome, and possibly as useful
      biomarkers. METHODS: Using the keywords schizophrenia, retina, pathology,
      electroretinogram (ERG), and/or optical coherence tomography (OCT) on PubMed, all
      studies using the English language within 30years were reviewed. Methods were
      examined, and common themes were identified, tabulated, and discussed. RESULTS:
      We classified the reports of retinal pathology into primary and secondary. The
      major secondary retinal pathology is related to the iatrogenic effects of a once
      widely prescribed first generation antipsychotic (thioridazine), which was found
      to be associated with retinal pigment deposits, decreased visual acuity, and
      suppression of dark adapted ERG responses. The primary retinal findings were
      obtained via different measures primarily using ERG, OCT, and microvascular
      imaging. The most consistent findings were 1) decreased ERG wave amplitudes, 2)
      reduced macular volume, 3) thinning of retinal nerve fiber layer, and 4) widened
      venule caliber. CONCLUSION: The abnormal pathobiological findings of the retina
      in schizophrenia may represent an important avenue for elucidating some of the
      neurodevelopmental aberrations in schizophrenia. The well replicated retinal
      anomalies could serve as biomarkers for schizophrenia and perhaps an
      endophenotype that may help identify at-risk individuals and to facilitate early
      intervention.

PMID- 28755879
TI  - Prospective Feasibility Trial of Sentinel Lymph Node Biopsy in the Setting of
      Inflammatory Breast Cancer.
AB  - BACKGROUND: Most inflammatory breast cancer (IBC) patients have axillary disease
      at presentation. Current standard is axillary lymph node dissection (ALND) after
      neoadjuvant chemotherapy (NACT). Advances in NACT have improved pathologic
      complete response (pCR) rates increasing interest in performing sentinel lymph
      node (SLN) biopsy (SLNB). Previous studies on SLNB for IBC patients did not
      assess nodal response with imaging or use dual tracer mapping. We sought to
      prospectively determine false negative rates of SLNB in IBC patients using dual
      tracer mapping, and to correlate pathology with preoperative axillary imaging.
      PATIENTS AND METHODS: Patients with IBC were prospectively enrolled. Patients
      underwent axillary staging with physical examination and axillary ultrasound
      before and after NACT. All patients underwent SLNB using blue dye and
      radioisotope, followed by ALND. RESULTS: Sixteen patients were prospectively
      enrolled. Clinical N stage was N0 in 1 patient, N1 in 8, and N3 in 7. SLN mapping
      was successful in only 4 patients (25%) with 12 (75%) not draining either tracer
      to a SLN. Three of the 4 (75%) who mapped had an axillary pCR. The patient who
      mapped but did not have an axillary pCR had a positive SLNB with additional
      axillary nodal disease identified on ALND. All patients who successfully mapped
      had presumed residual nodal disease on preoperative axillary ultrasound.
      CONCLUSION: SLNB was unsuccessful in most IBC patients. A small subset who have
      pCR might undergo successful SLNB, but preoperative axillary imaging failed to
      identify these patients. ALND should remain standard practice for IBC patients.

PMID- 28755878
TI  - Hyperprolactinaemia in first episode psychosis - A longitudinal assessment.
AB  - Little is known about hyperprolactinaemia (HPL) in first episode psychosis (FEP)
      patients. We investigated longitudinal changes in serum prolactin in FEP, and the
      relationship between HPL, and antipsychotic medication and stress. Serum
      prolactin was recorded in FEP patients at recruitment and again, 3 and 12months
      later. HPL was defined as a serum prolactin level >410mIU/L (~19.3ng/ml) for
      males, and a serum prolactin level >510mIU/L (~24.1ng/ml) for females. From a
      total of 174 people with serum prolactin measurements at study recruitment, 43%
      (n=74) had HPL, whilst 27% (n=21/78) and 27% (n=26/95) had HPL at 3 and 12months
      respectively. We observed higher serum prolactin levels in females versus males
      (p<0.001), and in antipsychotic treated (n=68) versus antipsychotic naive
      patients (p<0.0001). Prolactin levels were consistently raised in FEP patients
      taking risperidone, amisulpride and FGAs compared to other antipsychotics. No
      significant relationship was observed between perceived stress scores (beta=7.13,
      t=0.21, df=11, p=0.0.84 95% CI -72.91-87.16), or objective life stressors (beta=
      21.74, t=-0.31, df=8, p=0.77 95% CI -218.57-175.09) and serum prolactin. Our
      study found elevated rates of HPL over the course of the first 12months of
      illness. We found no evidence to support the notion that stress is related to
      elevated serum prolactin at the onset of psychosis.

PMID- 28755881
TI  - Let that posterior leaflet swing-but not too much!

PMID- 28755880
TI  - Should annuloplasty prosthesis be selected dependent on the location of prolapse
      in mitral valve repair for type II dysfunction?
AB  - OBJECTIVE: This study explored the influence of prosthesis selection on long-term
      outcomes in patients who underwent mitral valve repair for mitral insufficiency
      (MI) due to type II dysfunction. METHODS: We retrospectively reviewed 452
      patients with MI who underwent mitral valve repair for type II dysfunction
      between 2001 and 2014. Of these, 167 patients (37%) presented with anterior
      leaflet prolapse (anterior group) and 285 (63%) presented with posterior prolapse
      (posterior group). Full rings were applied in 95 patients (57%) in the anterior
      group and in 54 patients (19%) in the posterior group, and partial bands were
      applied in all others. We compared long-term outcome and change of MI severity
      over time between patients with partial-band and full-ring repair in the anterior
      and in the posterior groups using a mixed-effect model with repeated measures and
      propensity score-matched analysis. RESULTS: Ten-year survival of the cohort was
      90.5%. Echocardiography revealed MI >= 3 at follow-up in 58 patients (12.8%).
      Twenty-one patients (4.6%) required reoperation; freedom from reoperation was
      92.1% at 10 years. The MI severity over time in patients in the anterior group
      was higher than that in patients in the posterior group (P < .0001). Moreover, MI
      severity over time in patients with the partial band was higher than patients
      with the full ring in the anterior group (P = .0176). Propensity score-matched
      analysis in the anterior group, but not in the posterior group, revealed a
      significantly higher MI severity in patients with the partial band than those
      with the full ring over the study period (P = .04). CONCLUSIONS: Full-ring
      annuloplasty is indicated in the setting of anterior prolapse to prevent
      recurrent MI, whereas prosthesis type is not a determinant of recurrent MI in the
      setting of posterior prolapse.

PMID- 28755882
TI  - Pulmonary hypertension due to left heart disease causes intrapulmonary venous
      arterialization in rats.
AB  - OBJECTIVE: A rat model of left atrial stenosis-associated pulmonary hypertension
      due to left heart diseases was prepared to elucidate its mechanism. METHODS: Five
      week-old Sprague-Dawley rats were randomly divided into 2 groups: left atrial
      stenosis and sham-operated control. Echocardiography was performed 2, 4, 6, and
      10 weeks after surgery, and cardiac catheterization and organ excision were
      subsequently performed at 10 weeks after surgery. RESULTS: Left ventricular
      inflow velocity, measured by echocardiography, significantly increased in the
      left atrial stenosis group compared with that in the sham-operated control group
      (2.2 m/s, interquartile range [IQR], 1.9-2.2 and 1.1 m/s, IQR, 1.1-1.2, P < .01),
      and the right ventricular pressure-to-left ventricular systolic pressure ratio
      significantly increased in the left atrial stenosis group compared with the sham
      operated control group (0.52, IQR, 0.54-0.60 and 0.22, IQR, 0.15-0.27, P < .01).
      The right ventricular weight divided by body weight was significantly greater in
      the left atrial stenosis group than in the sham-operated control group (0.54
      mg/g, IQR, 0.50-0.59 and 0.39 mg/g, IQR, 0.38-0.43, P < .01). Histologic
      examination revealed medial hypertrophy of the pulmonary vein was thickened by
      1.6 times in the left atrial stenosis group compared with the sham-operated
      control group. DNA microarray analysis and real-time polymerase chain reaction
      revealed that transforming growth factor-beta mRNA was significantly elevated in
      the left atrial stenosis group. The protein levels of transforming growth factor
      beta and endothelin-1 were increased in the lung of the left atrial stenosis
      group by Western blot analyses. CONCLUSIONS: We successfully established a novel,
      feasible rat model of pulmonary hypertension due to left heart diseases by
      generating left atrial stenosis. Although pulmonary hypertension was moderate,
      the pulmonary hypertension due to left heart diseases model rats demonstrated
      characteristic intrapulmonary venous arterialization and should be used to
      further investigate the mechanism of pulmonary hypertension due to left heart
      diseases.

PMID- 28755883
TI  - Metformin: Insights into its anticancer potential with special reference to AMPK
      dependent and independent pathways.
AB  - Metformin has been known for its antidiabetic effects for decades and is used as
      a first line therapy in type 2 diabetes. But recently its anticancer potential
      has also been discovered. Metformin targets many pathways that play an important
      role in cancer cell proliferation and angiogenesis, mTORC1 signaling is a crucial
      pathway among them. Metformin inhibits mTORC1 via AMPK dependent and AMPK
      independent pathways, thereby inhibiting cancer cell growth and development.
      Encouraged by positive results of numerous preclinical studies on various types
      of cancer, many clinical trials are underway to study metformin's effect in
      chemoprevention and treatment of cancers in humans. Nowadays, applications of
      novel metformin analogues and nanotechnology based targeting have further
      enhanced the potential of metformin anticancer therapy. Here, we review both AMPK
      dependent and AMPK independent mechanisms involved in anticancer activity of
      metformin along with the outcome of preclinical and clinical studies.

PMID- 28755884
TI  - Comparison of oral versus intravenous application of tranexamic acid in total
      knee and hip arthroplasty: A systematic review and meta-analysis.
AB  - BACKGROUND: Tranexamic acid (TXA) is regarded as one of the most important drugs
      in reducing blood loss and hemoglobin (Hb) drop after total knee arthroplasty
      (TKA) or total hip arthroplasty (THA). Treatment with tranexamic acid (TXA) by
      intravenous application has been discussed extensively. Recently, several studies
      have reported that oral administration has an effect on blood sparing. Therefore,
      we performed a meta-analysis to investigate the efficacy and safety between oral
      TXA and intravenous TXA (IV-TXA) for blood sparing in total knee and hip
      arthroplasty. METHODS: Randomized controlled trials (RCTs) or retrospective
      cohort studies (RCSs) about relevant research were searched for by using PubMed
      (1996-April 2017), Embase (1980-April 2017), and the Cochrane Library (CENTRAL,
      April 2017). Five studies that compared oral with IV administration of TXA were
      included in our meta-analysis. Meta-analysis results were collected and analyzed
      by the software Review Manager 5.3 (Copenhagen: The Nordic Cochrane Center, The
      Collaboration, 2014). RESULTS: Five studies containing 3474 patients met the
      inclusion criteria. Our pooled data analysis indicated that oral TXA was as
      effective as the IV-TXA in terms of the average Hb drop (P = 0.88), total Hb loss
      (P = 0.57), total blood loss (P = 0.42), transfusion rate (P = 0.16),
      complications (P = 0.61), and length of hospital stay (P = 1.00). CONCLUSIONS:
      Compared with the IV-TXA method, oral TXA shows similar blood-sparing efficacy
      for preventing hemoglobin drop, total hemoglobin loss, and total blood loss
      following TKA or THA. In addition, no significant differences of transfusion
      rate, complications, or length of hospital stay were found between the 2 groups.
      However, because of the limited number of included studies, more studies of high
      quality are needed to further identify the optimal administration time for oral
      TXA.

PMID- 28755885
TI  - Supraclavicular block versus interscalene brachial plexus block for shoulder
      surgery: A meta-analysis of clinical control trials.
AB  - BACKGROUND: The ultrasound-guided interscalene block (ISB) has been considered a
      standard technique in managing pain after shoulder surgery. However, this method
      was associated with the incidence of hemi-diaphragmatic paresis. In contrast to
      ISB, supraclavicular block (SCB) was suggested to provide effective anaesthesia
      for shoulder surgery with a low rate of side-effects. Thus, we performed a meta
      analysis of randomised controlled trials (RCTs) to compare SCB with ISB for
      evaluating the efficacy and safety. METHOD: The literature was searched from
      PubMed, Wiley Online Library, EMBASE, and the Cochrane Library by two reviewers
      up to April 2017. All available RCTs written in English that met the criteria
      were included. Two authors pulled data from relevant articles and assessed the
      quality with the Cochrane Handbook. Review Manager 5.3 software was used to
      analyse the data. RESULTS: Five RCTs and one prospective clinical study met the
      eligibility criteria and were included in the meta-analysis. We considered that
      there were no statistically significant differences between supraclavicular and
      interscalene groups in procedural time (P = 0.81), rescue analgesia (P = 0.53),
      and dyspnoea (P = 0.6). The incidence of hoarseness and Horner syndrome was
      statistically lower in the SCB group than in the ISB group (P = 0.0002 and P <
      0.00001, respectively). CONCLUSION: The meta-analysis showed that ultrasound
      guided SCB could become a feasible alternative technique to the ISB in shoulder
      surgery.

PMID- 28755886
TI  - Pharmacological profile of mephedrone analogs and related new psychoactive
      substances.
AB  - BACKGROUND: Mephedrone is a synthetic cathinone and one of the most popular
      recreationally used new psychoactive substances. The aim of the present study was
      to characterize the in vitro pharmacology of novel analogs of mephedrone and
      related newly emerged designer stimulants. METHODS: We determined norepinephrine,
      dopamine, and serotonin transporter inhibition potencies and monoamine release in
      transporter-transfected human embryonic kidney 293 cells. We also assessed
      monoamine receptor and transporter binding affinities. RESULTS: Mephedrone
      analogs potently inhibited the norepinephrine transporter and, with the exception
      of 3-methylmethcathinone (3-MMC), inhibited the serotonin transporter more
      potently than the dopamine transporter. Similar to classic amphetamines,
      mephedrone analogs were substrate-type monoamine releasers. 5-(2
      Aminopropyl)indole (5-IT) was a highly potent monoamine transporter inhibitor and
      a releaser of dopamine and serotonin. 4-Methylamphetamine (4-MA) mediated efflux
      of all three monoamines and inhibited the serotonin transporter more potently
      than the dopamine transporter, unlike amphetamine. N-methyl-2-aminoindane (N
      methyl-2-AI) was a selective norepinephrine transporter inhibitor and
      norepinephrine releaser, whereas 5-methoxy-6-methyl-2-aminoindane (MMAI) was a
      selective serotonin transporter inhibitor and serotonin releaser. All of the
      drugs interacted with monoamine receptors. CONCLUSION: The predominant actions on
      serotonin vs. dopamine transporters suggest that dimethylmethcathinones, 4-MA,
      and MMAI cause entactogenic effects similar to 3,4-methylenedioxymethamphetamine,
      whereas 3-MMC, 5-IT, and N-methyl-2-AI have more stimulant-type properties like
      amphetamine. Because of pharmacological and structural similarity to mephedrone,
      similar health risks can be expected for these analogs. This article is part of
      the Special Issue entitled 'Designer Drugs and Legal Highs.'

PMID- 28755887
TI  - Brain temperature effects of intravenous heroin: State dependency, environmental
      modulation, and the effects of dose.
AB  - Here we examined how intravenous heroin at a dose that maintains self
      administration (0.1 mg/kg) affects brain temperature homeostasis in freely moving
      rats under conditions that seek to mimic some aspects of human drug use. When
      administered under standard laboratory conditions (quiet rest at 22  degrees C
      ambient temperature), heroin induced moderate temperature increases (1.0-1.5 
      degrees C) in the nucleus accumbens (NAc), a critical structure of the brain
      motivation-reinforcement circuit. By simultaneously recording temperatures in the
      temporal muscle and skin, we demonstrate that the hyperthermic effects of heroin
      results primarily from inhibition of heat loss due to strong and prolonged skin
      vasoconstriction. Heroin-induced brain temperature increases were enhanced during
      behavioral activation (i.e., social interaction) and in a moderately warm
      environment (29  degrees C). By calculating the "net" effects of the drug in
      these two conditions, we found that this enhancement results from the summation
      of the hyperthermic effects of heroin with similar effects induced by either
      social interaction or a warmer environment. When the dose of heroin was increased
      (to 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 mg/kg), brain temperature showed a biphasic
      down-up response. The initial temperature decrease was dose-dependent and
      resulted from a transient inhibition of intra-brain heat production coupled with
      increased heat loss via skin surfaces-the effects typically induced by general
      anesthetics. These initial inhibitory effects induced by large-dose heroin
      injections could be related to profound CNS depression-the most serious health
      complications typical of heroin overdose in humans.

PMID- 28755888
TI  - What are the long-term results 8 years after sleeve gastrectomy?
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) became the most frequent
      bariatric procedure performed in France (2011) and in the United States (2013),
      but studies reporting long-term results are still rare. SETTING: Private
      hospital, France. METHODS: This is a retrospective analysis of a prospective
      cohort of 168 patients who underwent LSG between 2005 and 2008. The objective of
      this study was to present the 8-year outcome concerning weight loss, modification
      of co-morbidities, and to report the revisional surgery after sleeve. RESULTS:
      The preoperative mean body mass index was 42.8 kg/m2 (31.1-77.9), 35 patients
      were super obese, and 64 patients had a previous gastric band. For LSG as a
      definitive bariatric procedure, 8 years of follow-up data were available for 116
      patients (follow-up: 69%). Of the remainder, 23 patients underwent revisional
      surgery and 29 were lost to follow-up. For the entire cohort, the mean excess
      weight loss (EWL) was 76% (0-149) at 5 years and 67% (4-135) at 8 years,
      respectively. Of the 116 patients with 8 years of follow-up, 82 patients had>50%
      EWL at 8 years (70.7%). Percentages of co-morbidities resolved were hypertension,
      59.4%; type 2 diabetes, 43.4%; and obstructive sleep apnea, 72.4%. Twenty-three
      patients had revisional surgery for weight regain (n = 14) or for severe reflux
      (n = 9) at a mean period of 50 months (9-96). Twelve patients underwent resleeve
      gastrectomy, 6 patients underwent conversion to a bypass, and 5 patients to
      duodenal switch (1 single anastomosis duodeno-ileostomy). A total of 31% of
      patients reported gastroesophageal reflux symptoms at 8 years. CONCLUSIONS: At 8
      years postoperatively, the LSG as a definitive bariatric procedure remained
      effective for 59% of cases. The results appear to be more favorable especially
      for the non-super-obese patients and primary procedures. LSG is a well-tolerated
      bariatric procedure with low long-term complication rates.

PMID- 28755889
TI  - Comment on: Is a "retained fundus" seen on postoperative upper gastrointestinal
      series after laparoscopic sleeve gastrectomy predictive of inferior weight loss?

PMID- 28755890
TI  - Paired editorial: Systematic review of transgastric ERCP in Roux-en-Y gastric
      bypass patients.

PMID- 28755891
TI  - Author's Response.

PMID- 28755893
TI  - Gender Empowerment Index: a choice of progress or perfection.

PMID- 28755894
TI  - Correction to Lancet Glob Health 2017; 5: e752-53.

PMID- 28755895
TI  - The SWPER index for women's empowerment in Africa: development and validation of
      an index based on survey data.
AB  - BACKGROUND: The Sustainable Development Goals strongly focus on equity. Goal 5
      explicitly aims to empower all women and girls, reinforcing the need to have a
      reliable indicator to track progress. Our objective was to develop a novel
      women's empowerment indicator from widely available data sources, broadening
      opportunities for monitoring and research on women's empowerment. METHODS: We
      used Demographic and Health Survey data from 34 African countries, targeting
      currently partnered women. We identified items related to women's empowerment
      present in most surveys, and used principal component analysis to extract the
      components. We carried out a convergent validation process using coverage of
      three health interventions as outcomes; and an external validation process by
      analysing correlations with the Gender Development Index. FINDINGS: 15 items
      related to women's empowerment were selected. We retained three components (50%
      of total variation) which, after rotation, were identified as three dimensions of
      empowerment: attitude to violence, social independence, and decision making. All
      dimensions had moderate to high correlation with the Gender Development Index.
      Social independence was associated with higher coverage of maternal and child
      interventions; attitude to violence and decision making were more consistently
      associated with the use of modern contraception. INTERPRETATION: The index, named
      Survey-based Women's emPowERment index (SWPER), has potential to widen the
      research on women's empowerment and to give a better estimate of its effect on
      health interventions and outcomes. It allows within-country and between-country
      comparison, as well as time trend analysis, which no other survey-based index
      provides. FUNDING: Bill & Melinda Gates Foundation.

PMID- 28755896
TI  - Clinical Genomics in Inflammatory Bowel Disease.
AB  - Genomic technologies inform the complex genetic basis of polygenic inflammatory
      bowel disease (IBD) as well as Mendelian disease-associated IBD. Aiming to
      diagnose patients that present with extreme phenotypes due to monogenic forms of
      IBD, genomics has progressed from 'orphan disease' research towards an integrated
      standard of clinical care. Advances in diagnostic clinical genomics are
      increasingly complemented by pathway-specific therapies that aim to correct the
      consequences of genetic defects. This highlights the exceptional potential for
      personalized precision medicine. IBD is nevertheless a challenging example for
      genomic medicine because the overall fraction of patients with Mendelian defects
      is low, the number of potential candidate genes is high, and interventional
      evidence is still emerging. We discuss requirements and prospects of explanatory
      and predictive clinical genomics in IBD.

PMID- 28755897
TI  - Gastrointestinal Mucormycosis After Orthotopic Liver Transplantation Presenting
      as Femoral Nerve Palsy: A Case Report and Review of the Literature.
AB  - Mucormycosis has emerged as a major threat to transplant recipients with high
      morbidity and mortality. This infection most commonly presents with rhino-sino
      orbital localization. Gastrointestinal mucormycosis is uncommon, with presenting
      symptoms usually abdominal in nature. Here, we describe the case of a liver
      transplant recipient who developed gastrointestinal mucormycosis with an initial
      manifestation of femoral nerve palsy, ultimately resulting in fungal
      dissemination and patient demise. This case highlights the challenges in making a
      timely diagnosis of mucormycosis, particularly in immunocompromised patients.

PMID- 28755898
TI  - Comparison of Hirschsprung-associated enterocolitis following Soave and Duhamel
      procedures.
AB  - BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) represents the primary
      cause of high morbidity and mortality in Hirschsprung disease (HSCR) patients.
      The most common surgical methods for HSCR are the Soave and Duhamel procedures.
      Therefore, we aimed to compare the HAEC frequency following the Soave and Duhamel
      procedures. METHODS: Medical records were retrospectively analyzed for patients
      who underwent the Soave and Duhamel pull-through at Dr. Sardjito Hospital,
      Indonesia from 2010 to 2015. The diagnosis of HAEC was determined using a HAEC
      scoring system. RESULTS: One hundred patients were involved (Soave: 52 males and
      19 females vs. Duhamel: 23 males and 6 females, p=0.62). There was significant
      difference in mean age at pull-through (Soave: 29.9+/-45.2 vs. Duhamel: 50.8+/
      47.5months, p=0.04), whereas mean age of HSCR diagnosis and pre-operative
      enterocolitis frequency did not differ significantly between groups (Soave:
      25.4+/-41.0 vs. Duhamel: 43.7+/-48.1months, p=0.06, and Soave: 7% vs. Duhamel:
      14%, p=0.44, respectively). The HAEC frequency after pull-through was
      significantly higher in the Duhamel than the Soave group (28% vs. 10%,
      respectively, p=0.03). Furthermore, pre-operative enterocolitis showed a
      significant association with HAEC following pull-through (p=2.0*10-4) and the
      risk of HAEC after Soave pull-through was increased in long-segment aganglionosis
      compared to short-segment HSCR (p=0.015). CONCLUSIONS: The frequency of HAEC was
      significantly higher after the Duhamel than the Soave procedure. Moreover,
      patients with pre-operative enterocolitis are prone to have HAEC following pull
      through. LEVEL OF EVIDENCE: III.

PMID- 28755899
TI  - The SERVE-HF safety notice in clinical practice - experiences of a tertiary sleep
      center.
AB  - BACKGROUND: In May 2015, the results of the SERVE-HF trial - addressing adaptive
      servoventilation (ASV) in chronic congestive heart failure (CHF) patients with
      central sleep apnea (CSA) - prompted a field safety notice. It was recommended to
      identify CHF patients treated with ASV and to advise the discontinuation of the
      treatment. We aimed to analyze the identification process and effect of ASV
      discontinuation on affected patients. METHODS: 126 patients treated with ASV on
      May 13th, 2015 at our institution were retrospectively analyzed. Treatment
      decisions, effect of ASV discontinuation and clinical course were followed for a
      year. Patients on ASV with CHF were compared to those without CHF. RESULTS: The
      risk criteria of the safety notice were fulfilled by 10.3% of patients (13/126).
      Additional echocardiographies were performed in 38%. ASV was discontinued in 93%
      of patients without adverse events (emergency hospitalization in n = 1). CSA
      reappeared immediately. Day- or nighttime symptoms were reported by 61%.
      Symptomatic patients were started on alternative treatments. CHF and non-CHF
      patients differed in cardiac function and type of SDB. CHF patients had shorter
      overall treatment duration. Compliance to ASV was similar in both groups with a
      median usage of 412 min (269; 495)/night in the CHF group and 414.5 min (347;
      480) in the non-CHF group. CONCLUSION: Identification of patients "at risk" is
      feasible but outcome of discontinuation of ASV cannot be evaluated based on these
      data. ASV withdrawal in patients with stable chronic CHF and CSA leads to an
      immediate return of sleep disordered breathing. Symptomatic patients may ask for
      alternative treatment options.

PMID- 28755901
TI  - Protein-energy wasting syndrome in advanced chronic kidney disease: prevalence
      and specific clinical characteristics.
AB  - INTRODUCTION: Protein-energy wasting (PEW) is associated with increased mortality
      and differs depending on the chronic kidney disease (CKD) stage and the dialysis
      technique. The prevalence in non-dialysis patients is understudied and ranges
      from 0 to 40.8%. OBJECTIVE: To evaluate the nutritional status of a group of
      Spanish advanced CKD patients by PEW criteria and subjective global assessment
      (SGA). PATIENTS AND METHODS: Cross-sectional study of 186 patients (101 men) with
      a mean age of 66.1+/-16 years. The nutritional assessment consisted of: SGA, PEW
      criteria, 3-day dietary records, anthropometric parameters and bioelectrical
      impedance vector analysis. RESULTS: The prevalence of PEW was 30.1%, with
      significant differences between men and women (22.8 vs. 33.8%, p < 0.005), while
      27.9% of SGA values were within the range of malnutrition. No differences were
      found between the 2methods. Men had higher proteinuria, percentage of muscle mass
      and nutrient intake. Women had higher levels of total cholesterol, HDL and a
      higher body fat percentage. The characteristics of patients with PEW were low
      albumin levels and a low total lymphocyte count, high proteinuria, low fat and
      muscle mass and a high Na/K ratio. The multivariate analysis found PEW to be
      associated with: proteinuria (OR: 1.257; 95% CI: 1.084-1.457, p=0.002),
      percentage of fat intake (OR: 0.903; 95% CI: 0.893-0.983, p=0.008), total
      lymphocyte count (OR: 0.999; 95% CI: 0.998-0.999, p=0.001) and cell mass index
      (OR: 0.995; 95% CI: 0.992-0.998). CONCLUSION: Malnutrition was identified in
      Spanish advanced CKD patients measured by different tools. We consider it
      appropriate to adapt new diagnostic elements to PEW criteria.

PMID- 28755900
TI  - Assessment of urinary TWEAK levels in Mexican patients with untreated lupus
      nephritis: An exploratory study.
AB  - OBJECTIVES: Urinary levels of TWEAK (uTWEAK) may be correlated with the degree of
      lupus nephritis (LN) activity. Our objective was to determine the sensitivity and
      specificity of uTWEAK in Mexican patients with untreated active lupus nephritis.
      METHODS: An exploratory study was performed; four groups of patients were
      analyzed as follows: 1) patients with systemic lupus erythematosus (SLE) without
      renal activity (SLE-LN), 2) patients with SLE with renal activity (SLE+LN), 3)
      patients with other types of glomerulopathy (glomerulonephritis, GMN), 4) and
      healthy patients (controls). RESULTS: In all, 44 patients, with an average age of
      35.9+/-11.5 years, were evaluated. uTWEAK levels were higher in patients with
      SLE+LN compared with patients in the other groups: SLE+LN 12.88+/-8.33, SLE-LN
      3.12+/-2.31, GMN 4.36+/-2.31 and controls 2.41+/-1.94pg/mg Cr (p=0.007). A total
      of 72.7% of the cases had renal activity index scores above 12, and 90.9% of the
      cases had scores of chronicity below 6 points. Receiver Operating Characteristic
      (ROC) curve analysis revealed that uTWEAK levels above 4.91pg/mg Cr had a
      sensitivity of 81% and a specificity of 75% for the diagnosis of renal activity
      due to lupus, with an area under the curve of 0.876 (95% CI: 0.75-0.99). However,
      no significant correlation was observed between the levels of uTWEAK and the
      histological findings specific to the activity and chronicity associated with
      SLE. CONCLUSIONS: Our study revealed that uTWEAK can adequately distinguish renal
      activity due to lupus, but cannot predict the degree of histological activity in
      Mexican patients with active lupus nephropathy.

PMID- 28755902
TI  - Low triiodothyronine is associated with elevation of N-terminal pro-brain
      natriuretic peptide (NT-proBNP) and mortality in dialysis patients.
AB  - BACKGROUND: Low thyroid hormone (TH) levels and myocardial damage are common in
      dialysis patients and are associated with mortality. However, little is known
      about the role of THs on myocardial damage as has been described in primary
      thyroid diseases. The aim of this study was to explore the potential relationship
      between low total triiodothyronine (total T3) and biomarkers of myocardial damage
      and the effect of their interaction on mortality, to ascertain if cardiovascular
      damage is the link between low THs and the risk of death in dialysis patients
      with CKD. MATERIAL AND METHODS: TH plasma levels, nutritional markers,
      inflammation and myocardial damage were studied in 296 patients undergoing
      peritoneal dialysis or haemodialysis, who were followed up for 16 months to
      ascertain the association between biochemical variables and mortality. RESULTS:
      Low total T3 levels were found in 45% of patients, which was inversely correlated
      with C-reactive protein (CRP) and NT-proBNP, and directly correlated with albumin
      and transferrin. Diabetes, CRP and total T3 were risk factors for all-cause
      mortality, and CRP, NT-proBNP and total T3 for cardiovascular mortality.
      CONCLUSIONS: Low total T3 levels are common in dialysis patients and are
      associated with inflammation, malnutrition and myocardial damage. The latter may
      be the link between low THs and all-cause and cardiovascular mortality.

PMID- 28755903
TI  - Tranexamic acid is associated with increased mortality in patients with
      physiological fibrinolysis.
AB  - BACKGROUND: Tranexamic acid (TXA) administration after trauma has not been proven
      to improve survival in the United States. Trauma patients were presented to the
      hospital with a spectrum of fibrinolytic activity, in which physiological levels
      of fibrinolysis are associated with the lowest mortality. We hypothesize that
      trauma patients who present to the hospital with physiological levels of
      fibrinolysis will have increased mortality if they receive TXA. MATERIALS AND
      METHODS: Severely injured trauma patients, followed prospectively from 2014 to
      2016, were included in the analysis. The patient's first thrombelastography was
      used to stratify patients into fibrinolysis phenotypes which included
      fibrinolysis shutdown, physiological fibrinolysis, and systemic
      hyperfibrinolysis. The primary outcome was in-hospital mortality. RESULTS: A
      total of 232 patients were analyzed (11% received TXA) with an overall mortality
      rate of 20%. TXA administration was associated with a higher new injury severity
      score (49 versus 28; P = 0.001), massive transfusion rate (69% versus 12%; P <
      0.001), and mortality (52% versus 17%; P < 0.001). Hyperfibrinolysis and shutdown
      had higher mortality rates than physiological group (24% versus 30% versus 14%; P
      = 0.050). The effect of TXA within phenotypes was not significant for shutdown
      (28% versus 38%; P = 0.604) but was significant in the physiological group (11%
      versus 63%; P < 0.001) and systemic hyperfibrinolysis (19% versus 55%; P =
      0.023). After adjusting for new injury severity score, TXA remained a significant
      predictor of mortality for patients with physiological fibrinolysis (P = 0.018).
      CONCLUSIONS: There was no clear benefit of receiving TXA in this study, and
      patients who present to the hospital with physiologic levels of fibrinolysis, who
      received TXA, had the highest mortality. The role of TXA in mature trauma systems
      remains unclear, and emerging data supports it may have adverse effects.

PMID- 28755904
TI  - Synthesis and application of molecularly imprinted polymers for the selective
      extraction of organophosphorus pesticides from vegetable oils.
AB  - The increasing use of pesticides in agriculture causes environmental issues and
      possible serious health risks to humans and animals. Their determination at trace
      concentrations in vegetable oils constitutes a significant analytical challenge.
      Therefore, their analysis often requires both an extraction and a purification
      step prior to separation with liquid chromatography (LC) and mass spectrometry
      (MS) detection. This work aimed at developing sorbents that are able to
      selectively extract from vegetable oil samples several organophosphorus (OPs)
      pesticides presenting a wide range of physico-chemical properties. Therefore,
      different conditions were screened to prepare molecularly imprinted polymers
      (MIPs) by a non-covalent approach. The selectivity of the resulting polymers was
      evaluated by studying the OPs retention in pure media on both MIPs and non
      imprinted polymers (NIP) used as control. The most promising MIP sorbent was
      obtained using monocrotophos (MCP) as the template, methacrylic acid (MAA) as the
      monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker with a
      molar ratio of 1/4/20 respectively. The repeatability of the extraction procedure
      and of the synthesis procedure was demonstrated in pure media. The capacity of
      this MIP was 1mg/g for malathion. This MIP was also able to selectively extract
      three OPs from almond oil by applying the optimized SPE procedure. Recoveries
      were between 73 and 99% with SD values between 4 and 6% in this oil sample. The
      calculated LOQs (between 0.3 and 2MUg/kg) in almond seeds with a SD between 0.1
      and 0.4MUg/kg were lower than the Maximum Residue Levels (MRLs) established for
      the corresponding compounds in almond seed.

PMID- 28755905
TI  - Mass-spectra-based peak alignment for automatic nontargeted metabolic profiling
      analysis for biomarker screening in plant samples.
AB  - Nontargeted metabolic profiling analysis is a difficult task in a routine
      investigation because hundreds of chromatographic peaks are eluted within a short
      time, and the time shift problem is severe across samples. To address these
      problems, the present work developed an automatic nontargeted metabolic profiling
      analysis (anTMPA) method. First, peaks from the total ion chromatogram were
      extracted using modified multiscale Gaussian smoothing method. Then, a novel peak
      alignment strategy was employed based on the mass spectra and retention times of
      the peaks in which the maximum mass spectral correlation coefficient path was
      extracted using a modified dynamic programming method. Moreover, an automatic
      landmark peak-searching strategy was employed for self-adapting time shift
      modification. Missing peaks across samples were grouped and registered into the
      aligned peak list table for final refinement. Finally, the aligned peaks across
      samples were analyzed using statistical methods to identify potential biomarkers.
      Mass spectral information on the screened biomarkers could be directly imported
      into the National Institute of Standards and Technology library to select the
      candidate compounds. The performance of the anTMPA method was evaluated using a
      complicated plant gas chromatography-mass spectrometry dataset with the aim of
      identifying biomarkers between the growth and maturation stages of the tested
      plant.

PMID- 28755906
TI  - Editorial Comment.

PMID- 28755907
TI  - [Chronic asthenia and abdominal pain in a 26-year-old woman].

PMID- 28755908
TI  - Communication Skills in Candidates for Accreditation in Rheumatology Are
      Correlated With Candidate's Performance in the Objective Structured Clinical
      Examination.
AB  - BACKGROUND: The Mexican Accreditation Council for Rheumatology annually certifies
      trainees in Rheumatology using a multiple-choice test and an objective structured
      clinical examination (OSCE). Since 2015, candidate's communication skills (CS)
      have been rated by both patients and by physician examiners and correlated with
      results on the OSCE. This study compared the CS from candidates to annual
      accreditation in Rheumatology as rated by patients and by physician examiners,
      and assessed whether these correlated with candidate's performance in the OSCE.
      MATERIAL AND METHODS: From 2015 to 2017, 8areas of CS were evaluated using a
      Likert scale, in each OSCE station that involved a patient. Both patient and
      physician evaluators were trained annually and their evaluations were performed
      blindly. The associations were calculated using the Pearson correlation
      coefficient. RESULTS: In general, candidates were given high CS scores; the
      scores from patients of the candidate's CS were better than those of physician
      examiners; within the majority of the stations, both scores were found to
      correlate moderately. In addition, the scoring of CS correlated with trainee
      performance at the corresponding OSCE station. Interestingly, better correlations
      were found when the skills were rated by the patients compared to physician
      scores. The average CS score was correlated with the overall OSCE performance for
      each trainee, but not with the multiple-choice test, except in the 2017
      accreditation process, when a weak correlation was found. CONCLUSIONS: CS
      assessed during a national accreditation process correlated with the candidate's
      performance at the station level and with the overall OSCE.

PMID- 28755909
TI  - Myositis as the initial presentation of panarteritis nodosa.
AB  - : A 47-year-old man presented with weight loss, bilateral calf pain, fever,
      hypertension, orchitis and oligoarthritis. Lab tests: anemia and elevated muscle
      enzymes. Resonance magnetic imaging: hyperintensity in gastrocnemius muscles
      (myositis). Histologic exam of the muscles: inflammatory infiltrate with atrophy
      and perifascicular regeneration. TREATMENT: methylprednisone (bolus) and
      cyclophosphamide. Muscle pain and swelling and difficulty in walking are common
      in panarteritis nodosa (PAN), whereas histologically demonstrated myositis is
      not. Even more rare is myositis as the initial presentation of this vasculitis.

PMID- 28755910
TI  - Reprint of "Fast and sensitive in vivo studies under controlled environmental
      conditions to substitute long-term field trials with genetically modified
      plants".
AB  - We introduce an easy, fast and effective method to analyze the influence of
      genetically modified (GM) plants on soil and model organisms in the laboratory to
      substitute laborious and time consuming field trials. For the studies described
      here we focused on two GM plants of the so-called 3rd generation: GM plants
      producing pharmaceuticals (PMP) and plant made industrials (PMI). Cyanophycin
      synthetase (cphA) was chosen as model for PMI and Choleratoxin B (CTB) as model
      for PMP. The model genes are expressed in transgenic roots of composite Vicia
      hirsuta plants grown in petri dishes for semi-sterile growth or small containers
      filled with non-sterile soil. No significant influence of the model gene
      expression on root induction, growth, biomass, interaction with symbionts such as
      rhizobia (number, size and functionality of nodules, selection of nodulating
      strains) or arbuscular mycorrhizal fungi could be detected. In vitro, but not in
      situ under field conditions, structural diversity of the bulk soil microbial
      community between transgenic and non-transgenic cultivars was determined by PLFA
      pattern-derived ratios of bacteria: fungi and of gram+: gram- bacteria.
      Significant differences in PLFA ratios were associated with dissimilarities in
      the quantity and molecular composition of rhizodeposits as revealed by Py-FIMS
      analyses. Contrary to field trials, where small effects based on the transgene
      expression might be hidden by the immense influence of various environmental
      factors, our in vitro system can detect even minor effects and correlates them to
      transgene expression with less space, time and labour.

PMID- 28755911
TI  - iTRAQ proteomic analysis of the interactions between Bombyx mori nuclear
      polyhedrosis virus and silkworm.
AB  - : The silkworm hemolymph is an important defense system against bacteria and
      viruses. In this study, silkworms were infected with Bombyx mori nuclear
      polyhedrosis virus to investigate the subsequent immune response at the protein
      level. Proteomes were analyzed before and after infection using isobaric tags for
      relative and absolute quantitation and LC-MS. A total of 456 differentially
      expressed proteins were identified, of which 179 were upregulated and 193 were
      downregulated. Changes in expression were validated by western blot for several
      proteins. Eleven of the differentially expressed proteins were involved in
      immunity. For example, modular serine protease and cecropin, which were
      downregulated, facilitate Toll and Imd signaling, while autophagy-related protein
      3, which was upregulated, protects cells against oxidative damage. Collectively,
      the data highlight the unique interactions of baculovirus with the silkworm
      immune system. BIOLOGICAL SIGNIFICANCE: This is the first time isobaric tags for
      relative and absolute quantitation were used to analyze B. mori proteins
      mobilized against B. mori nuclear polyhedrosis virus, and to investigate the
      immunity-associated proteome in B. mori. The results are a significant step
      towards a deeper understanding of immunoregulation in B. mori. SIGNIFICANCE: This
      is the first time isobaric tags for relative and absolute quantitation were used
      to analyze B. mori proteins mobilized against B. mori nuclear polyhedrosis virus,
      and to investigate the immunity-associated proteome in B. mori. The results are a
      significant step towards a deeper understanding of immunoregulation in B. mori.

PMID- 28755912
TI  - Examination of pathways involved in leukemia inhibitory factor (LIF)-induced cell
      growth arrest using label-free proteomics approach.
AB  - : Leukemia inhibitory factor (LIF) is a multifunctional highly glycosylated
      protein, synthesized and secreted in various body tissues. Besides the abundance
      in multiple organs, the molecular mechanism underlying the LIF interactions for
      cell survival and polarity is poorly understood. In the present study, high
      resolution LC-MS/MS based LFQ approach identified 2083 proteins with the overall
      PSM as 16,032. This proteomics data reviles that LIF promotes the AKT-mTOR
      signaling pathway. It induces cell growth arrest by an intracellular pathways
      loop to increase the half-life of the cell. Bioinformatics-based enrichment
      analysis revealed the involvement of LIF interacting partners in cell survival
      through increasing the cell cycle length. The anti-proliferative effect of LIF
      was confirmed by BrdU, MTT and Caspase 3/7 assays and further validated by RT
      qPCR. Till date to the best of our knowledge, this is the first study that
      elucidates LIF-mediated cascade of activation of MEK/ERK, Ras, mTOR, Hippo, and
      RAP1 pathways. This study further expands the repertoire of signaling pathways
      known to be subject to activation by LIF. These multiple involvements of pathways
      through autocrine-paracrine mediated cell cycle arrest additionally suggests a
      novel means for amplification of a growth arrest stimulus from LIF and its
      homolog's receptors. BIOLOGICAL SIGNIFICANCE: Leukemia inhibitory factor (LIF) is
      the polyfunctional cytokine and highly pleiotropic member of the interleukin-6
      family. It utilizes a receptor that consists of the LIF receptor b and gp130 and
      displays diverse effects on target cells. Despite well-known signal transduction
      mechanisms (JAK/STAT, MAPK, and PI3K) LIF also contains paradoxically opposing
      influences in several cell types which includes cellular stimulation, inhibition,
      proliferation, differentiation, and survival. LIF1 is also undergoing clinical
      trials as a driving force for the embryo implantation in the uterus in women who
      fail to become pregnant. As LIF can act on the broad spectrum of cell types, it
      is necessary to understand the basic response mechanism. The available non
      canonical regulatory pathways and molecular mechanism associated with LIF are
      poorly explained. Therefore, we have performed the global proteome analysis of
      LIF-mediated autocrine-paracrine signaling. The obtained data were examined
      through advanced bioinformatics tools and LIF inducible changes in terms of
      pathways were elucidated. The result showed the involvement of cluster of
      proteins maintaining the Ras/Rap1/STAT3/Hippo pathways which modify the protein
      component machinery of core histone complexes. This report describes the
      involvement of proteins responsible for cell growth and progression and defines
      the LIF-mediated novel autocrine-paracrine signaling loop for cell growth arrest.

PMID- 28755913
TI  - Comparative proteomics of matrix fractions between pimpled and normal chicken
      eggshells.
AB  - : Eggshell matrix can be dissociated into three matrix fractions: acid-insoluble
      matrix (M1), water-insoluble matrix (M2) and acid-water facultative-soluble
      matrix (M3). Matrix fractions from pimpled and normal eggshells were compared
      using label-free proteomic method to understand the differences among three
      matrix fractions and the proteins involved with eggshell quality. A total of 738
      and 600 proteins were identified in the pimpled and normal calcified eggshells,
      respectively. Both eggshells showed a combined proteomic inventory of 769
      proteins. In the same type of eggshell, a high similarity was present in the
      proteomes of three matrix fractions. These triply overlapped common proteins
      formed the predominant contributor to proteomic abundance in the matrix
      fractions. In each matrix fraction and between both eggshell models, normal and
      pimpled eggshells, a majority of the proteomes of the fractions were commonly
      observed. Forty-two common major proteins (iBAQ-derived abundance >=0.095% of
      proteomic abundance) were identified throughout the three matrix fractions and
      these proteins might act as backbone constituents in chicken eggshell matrix.
      Finally, using 1.75-fold as up-regulated and using 0.57-fold as down-regulated
      cutoff values, twenty-five differential major proteins were screened and they all
      negatively influence and none showed any effect on eggshell quality. Overall, we
      uncovered the characteristics of proteomics of three eggshell matrix fractions
      and identified candidate proteins influencing eggshell quality. The next research
      on differential proteins will uncover the potential mechanisms underlying how
      proteins affect eggshell quality. BIOLOGICAL SIGNIFICANCE: It was reported that
      the proteins in an eggshell can be divided into insoluble and soluble proteins.
      The insoluble proteins are thought to be an inter-mineral matrix and acts as a
      structural framework, while the soluble proteins are thought as intra-mineral
      matrix that are embedded within the crystal during calcification. However, the
      difference between matrix fractions is unknown. Cross-analysis of proteomic data
      of three matrix fractions from the same type of eggshell, uncovered triply
      overlapped common proteins formed the predominant contributor to proteomic
      abundance of any matrix fraction, and we suggested that abundance variance of
      some common proteins between the three matrix fractions might be an important
      cause of their solubility differences. Moreover, eggshell is formed in hen's
      uterus, and uterus tend to be considered as unique organ determining eggshell
      quality. By cross-analysis on proteomic data of three matrix fractions between
      two eggshell models, normal and pimpled eggshells, the differential proteins were
      screened as candidates influencing eggshell quality. And we suggested that the
      liver and spleen or lymphocytes might be the major organs influencing eggshell
      quality, because the most promising candidates are almost blood and non
      collagenous proteins, and originated from above organs.

PMID- 28755914
TI  - Cochlear Nerve Action Potential Monitoring for Preserving Function of an Unseen
      Cochlear Nerve in Vestibular Schwannoma Surgery.
AB  - BACKGROUND: Intraoperative monitoring of cochlear nerve action potential (CNAP)
      has been used in patients with small vestibular schwannoma (<15 mm) to preserve
      cochlear nerve function. We performed surgery for a larger vestibular schwannoma
      under CNAP monitoring with the aim of preserving cochlear nerve function, and
      compared the data with findings from 10 patients with hemifacial spasm who
      underwent microvascular decompression surgery. CASE DESCRIPTION: We report the
      case of a patient with a 26-mm vestibular schwannoma and normal hearing function
      who underwent neurosurgery under electrophysiological monitoring of the facial
      and cochlear nerves. Amplitudes of evoked facial muscle responses were maintained
      at approximately 70% during the operation. The latency of wave V on brainstem
      auditory evoked potential (BAEP) increased by 0.5 ms, and amplitude was
      maintained at approximately 70% of the value at the beginning of the operation.
      Latencies of P1, N1, and P2 on CNAP did not change intraoperatively. These
      latencies were comparable to those of 10 normal patients with hemifacial spasm.
      CNAP monitoring proved very useful in confirming the location of the cochlear
      nerve in the operative field and preserving cochlear nerve function. Both facial
      nerve function and hearing acuity were completely preserved after tumor removal,
      and wave V latency on BAEP returned to normal and was maintained in the normal
      range for at least 2 years. CONCLUSIONS: CNAP monitoring is extremely useful for
      preserving the function of the unseen cochlear nerve during vestibular schwannoma
      surgery.

PMID- 28755915
TI  - Use of Sodium Fluorescein in Meningioma Surgery Performed Under the YELLOW-560 nm
      Surgical Microscope Filter: Feasibility and Preliminary Results.
AB  - OBJECTIVE: To evaluate the feasibility of sodium fluorescein (Na-Fl)-guided
      surgery involving the use of the PENTERO 900 surgical microscope equipped with
      the YELLOW-560 nm filter and low-dose Na-FL (200 mg/2-4 mg/kg) in meningioma
      surgery. PATIENTS AND METHODS: The study included 30 patients with newly
      diagnosed or recurrent meningiomas who underwent Na-Fl-guided surgery between
      April 2015 and December 2016. Clinical features, surgical observations, extent of
      resection, and tumor histopathology were retrospectively analyzed. The Na-Fl
      enhancement pattern was assessed as "no enhancement," "diffuse homogenous
      enhancement," or "low heterogeneous enhancement." RESULTS: There were 30
      meningiomas among the 30 patients. In 25 patients, Na-Fl was used for tumor
      demarcation, whereas in 5 patients, it was used for videoangiography. In this
      series, 88% of tumors showed diffuse homogeneous Na-Fl enhancement during the
      operation. The resection rate of the meningiomas was 87%. In 5 patients, in whom
      Na-Fl was used for videoangiography, the approach was useful to evaluate Na-Fl
      stained vessels for patency and to understand their relationship with the tumor.
      No adverse events were encountered with regard to Na-Fl use. CONCLUSIONS: Na-Fl
      guidance with the use of the YELLOW-560 filter is safe and effective during
      meningioma surgery.

PMID- 28755916
TI  - Emerging Markers of Early Brain Injury and Delayed Cerebral Ischemia in
      Aneurysmal Subarachnoid Hemorrhage.
AB  - BACKGROUND: Delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage is
      characterized by a highly complex pathophysiology and results in neurologic
      deterioration after the inciting bleed. Despite its significant consequences,
      prompt diagnosis can be elusive and treatment is often administered too late.
      Early brain injury, which occurs within the first 72 hours after ictus, may be an
      important factor for delayed cerebral ischemia and poor overall outcome. Here, we
      explore the purported clinical and pathologic manifestations of early brain
      injury to identify biomarkers that could have prognostic value. METHODS: We
      review the literature and discuss potential emerging markers of delayed cerebral
      ischemia in the context of early brain injury. RESULTS: The following clinical
      features and biomarkers were examined: global cerebral edema, ictal loss of
      consciousness, ultra early angiographic vasospasm, continuous
      electroencephalogram monitoring, systemic inflammatory response syndrome,
      cellular mediators of the inflammatory response, and hematologic derangements.
      CONCLUSIONS: Some of these markers possess independent value for determining the
      risk of complications after aneurysmal subarachnoid hemorrhage. However, their
      use is limited because of a variety of factors, but they do provide an avenue of
      further study to aid in diagnosis and management.

PMID- 28755917
TI  - Postoperative Radiculopathy Caused by a Retained Fractured Pedicle Cannulation
      Probe and Its Mechanism of Extraction.
AB  - BACKGROUND: Spine surgery relies heavily on technology and surgical
      instrumentation. Improperly used instrumentation can be detrimental to the
      patient. Despite multiple checkpoints to ensure that foreign bodies are not
      retained in surgery, numerous case reports have described retained foreign
      bodies; however, none of these cases involve retained instrumentation after open
      spine surgery. Of the retained objects, 4 were sponges and one was a Jamshidi
      needle fragment. Although smaller objects are more commonly the culprits,
      surgical instruments can break off, remain stuck, and cause clinical sequelae.
      CASE DESCRIPTION: This case presents a retained fractured pedicle finder as the
      cause of right L5 radiculopathy. To our knowledge, this report is the first to
      describe an instrumentation-associated postoperative radiculopathy. Because of
      the strength with which the object was impacted, its extraction proved difficult.
      CONCLUSIONS: The technique of removal using a mallet and osteotome in 4
      directions to loosen its hold in the vertebral body. Attempts and eventual
      successful removal are described.

PMID- 28755918
TI  - Indeterminate Dendritic Cell Tumor in Thoracic Spine: A Case Report.
AB  - BACKGROUND: Indeterminate dendritic cell tumor (IDCT) is an extremely rare
      hematologic disorder with poorly understood pathogenesis. Occasionally
      encountered by hematologists, unusual presentations of IDCT have not been
      reported in the spine literature. METHODS: We report a 51-year-old man who
      presented with a 3-month history of progressively worsening axial thoracic back
      pain radiating to his sides. Magnetic resonance imaging revealed a 3-cm enhancing
      mass at the T9 vertebral body with an exophytic component causing significant
      canal stenosis. Initial percutaneous biopsy revealed histiocytic sarcoma.
      RESULTS: The patient underwent exploratory thoracotomy and en bloc resection of
      the lesion with T8-10 fusion. Final pathology results revealed IDCT with
      fibrosis. IDCT immunostaining was partially positive for Langerhans cell marker
      (positive for S100 and CD1a, but lacked Birbeck granules and Langerin stain) and
      partially positive for blastic plasmacytoid dendritic cell neoplasm.
      Additionally, it was positive for CD45, CD68, and CD163. Lymphadenopathy was
      absent in this patient. CONCLUSIONS: Although first reported in the 1980s, IDCT
      has been omitted from most classifications owing to its rarity. Hematologists
      have debated the cell of origin; it is believed to comprise pre-Langerhans cells,
      as Birbeck granules are acquired after migration to the epidermis. IDCT remains
      of indeterminate origin. We report the first case of spinal IDCT. Familiarity
      with the histologic features is warranted to ensure accurate diagnosis and
      appropriate treatment.

PMID- 28755919
TI  - Use of Laser in Arteriovenous Malformation Surgery.
AB  - BACKGROUND: Arteriovenous malformation surgery is particularly demanding owing to
      the need to control bleeding of small, deep white matter vessels during and after
      removal of the nidus; this is probably one of the most critical moments of
      arteriovenous malformation surgery. The aim of this article is to describe a
      useful technique based on the use of tweezers to temporarily stop the blood flow
      followed by coagulation with the thulium laser. METHODS: Surgery was performed in
      20 patients with unruptured cerebral arteriovenous malformations. In each case,
      the superficial feeder vessels were easily coagulated with nonstick bipolar tips.
      The finer and deeper feeder vessels were coagulated with use of tweezers and
      thulium laser. RESULTS: All patients were treated successfully. Optimal
      intraoperative hemostasis was achieved. CONCLUSIONS: Results were good with no
      postoperative complications. Our results could encourage a more standardized use
      of the described technique.

PMID- 28755920
TI  - External Ventricular Drainage Preceding the Removal of a Nail from the
      Intracranial Space as a Safe Management Strategy for Predicted Secondary
      Intraventricular Hemorrhage.
AB  - BACKGROUND: Intracranial nail gun injury is a rare traumatic event and can result
      from a suicide attempt. Cerebral angiography is essential in the evaluation of
      damage to the intracranial vessels, and surgical removal of nails is generally
      the optimal treatment. Intraventricular hemorrhage can happen after removal of
      intracranial nails. Endovascular surgery or intraoperative computed tomography
      has been reported to be useful for detection and treatment of intraventricular
      hemorrhage. After the surgical removal of nails, attention should be paid for
      complications such as pseudoaneurysm and infection. CASE DESCRIPTION: A 63-year
      old man with a history of depression was transferred to our hospital in an
      unconscious state. Physical examination showed 2 nails puncturing his left
      thorax, and computed tomography revealed a nail puncturing the intracranial
      space. No damage to these intracranial vessels was observed on computed
      tomography angiography and venography. After drainage for potential
      intraventricular hemorrhage, the nails were removed. Postoperatively,
      prophylactic antibiotic therapy was administrated for secondary infection.
      Computed tomography angiography did not detect any postoperative pseudoaneurysms.
      The patient also underwent therapy from a psychiatrist and was transferred to
      another hospital. CONCLUSIONS: As for treatment of a case of intracranial nail
      gun injury, our case shows that preoperative cerebral angiography is not always
      needed in intracranial nail gun injury when there is no apparent damage to the
      intracranial vessels and emergent removal of nails is required. External
      ventricular drainage preceding the removal of a puncture object can be an
      effective management strategy for secondary intraventricular hemorrhage.

PMID- 28755921
TI  - Corrigendum to "When do species-tree and concatenated estimates disagree? An
      empirical analysis with higher-level scincid lizard phylogeny". [Mol. Phylogen.
      Evol. 82A (2015) 146-155].

PMID- 28755922
TI  - Brachytherapy improves outcomes in young men (<=60 years) with prostate cancer: A
      SEER analysis.

PMID- 28755923
TI  - Proximal sacral deformity: a common element in lytic isthmic spondylolisthesis at
      L5 and in degenerative spondylolisthesis at L4-L5 segment. Two apparently very
      different etiopathogenic entities.
AB  - A radiographic study was carried out to investigate the relationship between
      proximal sacral sagittal anatomy (either kyphosis or lordosis) and either isthmic
      or degenerative spondylolisthesis. In addition, we studied whether there is a
      relationship between proximal sacral kyphosis and the degree of such listhesis in
      the case of L5 isthmic spondylolisthesis. Lateral standing x-rays were used from
      173 patients, ninety of whom had degenerative spondylolisthesis L4-L5, and eighty
      three an isthmic spondylolisthesis of L5 (67 low-grade and 16 high-grade) and
      compared with a control group of 100 patients adjusted by age and gender, without
      any type of spondylolisthesis. Listhesis was graded using Meyerding's
      classification and the proximal sacral kyphosis angle (CSP) was measured between
      S1 and S2 posterior walls, according to Harrison's method. In our series, there
      was a proximal sacral kyphosis in both types of spondylolisthesis, greater in the
      lytic type. By contrast, the control group had a proximal sacral lordosis. The
      differences were statistically significant. Therefore, we concluded that there
      was a proximal sacral kyphosis in patients with both degenerative and isthmic
      lytic spondylolisthesis, but with our results, we were not able to ascertain
      whether it is a cause or a consequence of this listhesis.

PMID- 28755924
TI  - Ankle tuberculosis. A case in childhood.
AB  - Articular tuberculosis of the ankle joint is a rare presentation of skeletal
      tuberculosis (10% of cases). This unusual location and the low index of clinical
      suspicion leads to delays in diagnosis and treatment. Radiographic and analytic
      studies are unspecific in the first stage. CAT and MRI are useful in diagnosis.
      Chemotherapy is the mainstay of treatment and surgery is often required to
      establish the diagnosis and in the treatment. We report a case of ankle
      tuberculosis in a 22 month-old child. The diagnosis was confirmed by synovial
      biopsy. There was no patient or family contact with tuberculosis patients. There
      was no risk factor. There was no lung disease. Diagnosis was made 1 year after
      onset of symptoms. The treatment was with chemotherapy and surgery was performed
      as preventive treatment of equinus deformity and osteoarthritis. Good clinical
      and functional outcome was achieved after 20 years of follow up.

PMID- 28755925
TI  - A Flow Imaging Microscopy-Based Method Using Mass-to-Volume Ratio to Derive the
      Porosity of PLGA Microparticles.
AB  - The release of drugs from poly(lactic-co-glycolic acid) (PLGA) microparticles
      depends to a large extent on the porosity of the particles. Therefore, porosity
      determination of PLGA microparticles is extremely important during pharmaceutical
      product development. Currently, mercury intrusion porosimetry (MIP) is widely
      used despite its disadvantages, such as the need for a large amount of sample
      (several hundreds of milligrams) and residual toxic waste. Here, we present a
      method based on the estimation of the volume of a known mass (a few milligrams)
      of particles using micro-flow imaging (MFI) to determine microparticle batch
      porosity. Factors that are critical for the accuracy of this method (i.e.,
      density of the suspending fluid, particle concentration, and postsample rinsing)
      were identified and measures were taken to minimize potential errors. The
      validity of the optimized method was confirmed by using nonporous
      polymethylmethacrylate microparticles. Finally, the method was employed for the
      analysis of 7 different PLGA microparticle batches with various porosities (4.0%
      51.9%) and drug loadings (0%-38%). Obtained porosity values were in excellent
      agreement with the MIP-derived porosities. Altogether, the developed MFI-based
      method is a valuable tool for deriving the total volume of a known mass of PLGA
      particles and therewith their porosity.

PMID- 28755926
TI  - Sliding mode control for generalized robust synchronization of mismatched
      fractional order dynamical systems and its application to secure transmission of
      voice messages.
AB  - This paper proposes a generalized robust synchronization method for different
      dimensional fractional order dynamical systems with mismatched fractional
      derivatives in the presence of function uncertainty and external disturbance by a
      designing sliding mode controller. Based on the proposed theory of generalized
      robust synchronization criterion, a novel audio cryptosystem is proposed for
      sending or sharing voice messages secretly via insecure channel. Numerical
      examples are given to verify the potency of the proposed theories.

PMID- 28755927
TI  - Short communication: Repeated mammary tissue collections during lactation do not
      alter subsequent milk yield or composition.
AB  - Mammary biopsy collection (MB) is a valuable approach for studying mammary gland
      biology, but it is unclear if repeated MB impair the performance of lactating
      dairy cows. The objective of this trial was to examine the effect of repeated MB
      during lactation on udder health, dry matter intake (DMI), and lactation
      performance of lactating dairy cows. Sixty-four multiparous, mid-lactation
      Holstein cows were enrolled in a 29-wk trial, and 32 cows were randomly selected
      for repeated MB. The MB and non-MB (NMB) cows had similar parity (2.6 +/- 0.9)
      and days in milk (96.5 +/- 56.3 d) at enrollment. All animals were housed in the
      same barn and managed in the same manner. Cows were milked 3 times daily with
      milk yield recorded at each milking. Milk composition was measured weekly and DMI
      recorded daily. Three MB were performed per cow: 1 wk after enrollment and at 15
      and 24 wk. The first and third MB were performed on the left rear quarter,
      whereas the second MB was on the right rear quarter. The MB were performed based
      on previously described procedures using a rotating stainless steel cannula with
      a retractable blade connected to a cordless drill, with appropriate sedation and
      antiseptic treatment after each MB. After MB, udder health, surgical wound
      healing, and presence of blood in milk were visually examined at each milking.
      Blood was cleared from milk 3.86 +/- 2.0 d after MB. During the experiment, 4
      rear quarters of MB cows and 5 rear quarters from NMB cows were diagnosed and
      treated for clinical mastitis. No differences were observed in DMI, milk yield,
      somatic cell score, or milk concentration and yields of fat, protein, lactose,
      and solids-not-fat between MB and NMB. In conclusion, lactating cows recover
      rapidly from MB, and repeated MB have no long-term effects on DMI, milk yield and
      composition, or udder health of lactating dairy cows.

PMID- 28755928
TI  - Stabilization of milk proteins in acidic conditions by pectic polysaccharides
      extracted from soy flour.
AB  - Pectic polysaccharides were extracted from soy flour at either room temperature
      (SPRT) or 121 degrees C (SPH), and their abilities to stabilize milk proteins in
      acidic conditions were evaluated. Both SPRT and SPH were found to contain
      proteinaceous components that were difficult to dissociate from polysaccharide
      components using size exclusion chromatography, whereas the molar mass of the
      former was approximately twice that of the latter. Due to the higher molar mass,
      SPRT was expected to provide stronger steric effects to prevent aggregation
      between milk proteins in acidic conditions than SPH. Alkaline treatment of SPRT
      for breaking O-linkages between AA and monosaccharide residues decreased its
      molar mass by approximately 160 kDa, indicating that they contained naturally
      occurring conjugates of pectic and proteinaceous moieties. Particle size
      distributions in simulated acidified milk drink samples containing 0.2% SPRT or
      SPH showed monomodal distributions with median diameters of around 1.2 MUm at pH
      4. The presence of large protein aggregates (~5 MUm) was detected at 0.2% SPRT
      and pH 3.2, 0.6 to 0.8% SPRT and pH 4, or 0.2% SPH and pH 3.4. The presence of
      excess polysaccharide molecules unbound to proteins was detected at 0.2% SPRT and
      pH 3.2 to 3.4, 0.4 to 0.8% SPRT and pH 4, 0.2% SPH and pH 3.4 to 3.6, and 0.4 to
      0.8% SPH and pH 4. The present results suggest that molecular characteristics of
      pectic polysaccharides vary depending on extraction conditions and hence their
      functional behavior.

PMID- 28755929
TI  - Development of a new real-time quantitative PCR assay for the detection of
      Staphylococcus aureus genotype B in cow milk, targeting the new gene adlb.
AB  - The specific and reliable diagnosis of mastitis pathogens is essential for
      successful sanitation programs. The aim of the present study was to develop and
      evaluate a new real-time quantitative PCR (qPCR) assay for the very sensitive and
      specific detection of Staphylococcus aureus genotype B in cow milk samples. This
      mastitis pathogen is contagious and particularly prevalent in Switzerland and
      other central European countries. The new test is based on a rapid preparation of
      bacteria, followed by DNA isolation and qPCR for a unique target gene coding for
      the adhesion-like bovine protein (adlb). The inclusivity of the new target gene
      was 97% and the exclusivity 98%, meaning that other genotypes and bacterial
      species could be excluded with high reliability. The limit of detection of the
      new assay was 235 staphylococcal cell equivalents/mL of culture. The new test
      shows high intra- and interassay repeatability. Results are available within 2 d
      after sampling, allowing farmers and veterinarians to apply sanitation measures
      immediately. Based on the results of a preliminary field study, the diagnostic
      sensitivity and specificity of the new qPCR assay are 99 and 100%, respectively.
      The new analytical procedure is straightforward and can be applied for routine
      diagnostics.

PMID- 28755930
TI  - Locomotion characteristics of dairy cows walking on pasture and the effect of
      artificial flooring systems on locomotion comfort.
AB  - The locomotion comfort of dairy cows depends on the floor of the walking alleys.
      Optimal locomotion comfort is given when cows walk on pasture, allowing freedom
      from discomfort and pain and the expression of normal behavior. This study
      examined the characteristics of locomotion behavior on pasture (gold standard
      with optimal locomotion comfort) and compared it with behaviors of cows walking
      on mastic asphalt or solid rubber mats before and after a routine claw trimming
      session. Our hypotheses were (1) that gait variables were different on pasture
      versus mastic asphalt and on mastic asphalt versus rubber, and (2) that claw
      trimming had an effect on gait variables of cows walking on mastic asphalt.
      Twenty-four dairy cows kept in a tiestall facility were enrolled in this
      experimental trial. The pedogram was measured using 2 standalone 3-dimensional
      accelerometers (400 Hz), attached to the metatarsus of both hind limbs. The
      extracted pedogram variables included temporal events (kinematic outcome = gait
      cycle and stance-phase and swing-phase durations) and peaks (kinetic outcome =
      foot load, toe-off). The cows were further video-recorded to calculate walking
      speed and stride length. Locomotion score was performed on mastic asphalt to
      enroll only nonlame cows (locomotion score <3). For comparison between different
      floor types, repeated-measures ANOVA was performed with the cow as a subject
      variable, session time of measurement as within-subject variable, and flooring
      type as a fixed effect. Three separate analyses were performed: pasture versus
      mastic asphalt (analysis I), solid rubber versus mastic asphalt (analysis II),
      and the effect of claw trimming on the kinematic and kinetic variables on mastic
      asphalt (analysis III). All tested gait variables were significantly different
      between pasture and mastic asphalt floor. The optimal characteristics of
      locomotion comfort on pasture included shorter duration of gait cycle, longer
      stance-phase duration, shorter swing-phase duration, higher walking speed, longer
      stride length, and higher peaks of foot load and toe-off. However, gait variables
      of cows walking on rubber mats did not show any significant difference compared
      with the mastic asphalt floor; only stride length tended to be longer on rubber
      mats. In addition, the stance- and swing-phase durations significantly improved
      shortly after trimming. The left-right differences of the stance- and swing-phase
      durations tended to decrease after claw trimming when cows walked on asphalt
      floor. The results of this study show that solid rubber flooring does not result
      in significant improvement of the evaluated variables of locomotion comfort
      compared with mastic asphalt.

PMID- 28755931
TI  - Blood plasma traits associated with genetic merit for feed utilization in
      Holstein cows.
AB  - The objective of this study was to evaluate the potential of selection for feed
      utilization on associated blood plasma metabolite and hormone traits. Dry matter
      intake (DMI) was recorded in 970 Holsteins from 11 commercial farms in
      Pennsylvania and used to derive dry matter efficiency (DME; fat-corrected milk
      yield/DMI), crude protein efficiency (CPE; protein yield/crude protein intake),
      and residual feed intake (RFI, defined as actual feed intake minus expected feed
      intake for maintenance and milk production, based on calculation of DMI adjusted
      for yield, body weight, and body condition score). Estimated breeding values for
      the 4 feed utilization traits (DMI, DME, CPE, and RFI), yield traits, body
      traits, and days open were standardized according to their respective genetic
      standard deviations. Up to 631 blood samples from 393 cows from 0 to 60 d in milk
      (DIM) were evaluated for blood plasma concentrations of glucose, nonesterified
      fatty acids (NEFA), beta-hydroxybutyrate (BHB), creatinine, urea, growth hormone
      (GH), 3,5,3'-triiodothyronine (T3), and other parameters. Blood plasma traits
      were regressed on DIM, lactation number, herd, and standardized genetic merit.
      Cows with higher genetic merit for yield had significantly higher concentrations
      of GH, NEFA (milk and protein yield), and BHB (fat yield) from 31 to 60 DIM, but
      lower concentrations of glucose from 0 to 30 DIM, and T3 (milk yield, 0-60 DIM).
      The high GH-low glucose-low T3 concentration pattern was further accentuated for
      cows with genetic merit for enhanced feed efficiency (higher DME and lower RFI).
      Cows with a genetic tendency to be thin (low body condition score) also had
      elevated GH concentrations, but lower blood glucose, creatinine, and T3
      concentrations. Those characteristics associated with enhanced feed efficiency
      (higher GH and lower glucose and T3 concentrations) were unfavorably associated
      with fertility, as indicated by elevated days open. Elevated NEFA and BHB
      concentrations were also associated with extended days open. Consideration of
      metabolic profiles when evaluating feed efficiency might be a method of
      maintaining high levels of health and reproductive fitness when selecting for
      feed efficiency.

PMID- 28755932
TI  - Relationships between postruminal casein infusion and milk production, and
      concentrations of plasma amino acids and blood urea in dairy cows: A multilevel
      mixed-effects meta-analysis.
AB  - The relationships between postruminal casein infusion and production variables
      and concentrations of plasma AA and blood urea were evaluated using multilevel
      mixed-effects models derived from literature data collected in dairy cows. The
      data set contained 147 treatment means [i.e., 66 controls (CTL) and 81 casein
      infused (CAS) means]. Each CAS mean was paired with its corresponding CTL mean to
      create 81 mean differences (CAS minus CTL), which were analyzed as absolute and
      percentage-based units (i.e., percentage increase or decrease in CAS relative to
      CTL). The primary variable of interest was the difference in estimated
      metabolizable protein (MP) supply (DeltaMP) between CAS and CTL. The other
      explanatory variables were based on levels in CTL: MP supply, MP balance, the
      ratio of duodenal microbial protein (MCP) to MP supply (MCPMP), the stage of
      lactation (early or mid/late) and the type of forage (grass/legume- or corn
      silage-based). The MP supply and MP balance influenced negatively the
      relationship between DeltaMP and the response of true protein yield. Responses of
      milk urea, blood urea, and plasma urea cycle AA concentrations were associated
      positively with DeltaMP, indicating that a large amount of infused AA was
      catabolized to urea. Responses of plasma essential AA concentrations were related
      positively to DeltaMP. The relative effect of DeltaMP was highest for responses
      of plasma His concentration in cows fed grass/legume-based diets and at high
      MCPMP ratios. This relationship suggests that positive responses of plasma His
      concentrations are associated with diets relying heavily on microbial protein
      synthesis (high MCP), low in crude protein (low estimated MP supply), or both.
      The relationship between DeltaMP and responses of plasma group 2 AA (Ile, Leu,
      Lys, and Val) concentrations was approximately 2 times greater than that for
      group 1 AA (His, Met, and Phe+Tyr) at mean MCPMP and MP supply. This could
      reflect the low hepatic removal group 2 AA compared with group 1 AA in dairy
      cows. Collectively, these results provide novel information on how dietary and
      cow conditions may alter responses to protein supplementation.

PMID- 28755933
TI  - Deviations in behavior and productivity data before diagnosis of health disorders
      in cows milked with an automated system.
AB  - To explore potential changes in behavior and productivity useful for early
      detection of health disorders in cows milked with automated milking systems
      (AMS), we collected longitudinal data throughout lactation of 57 dairy cows
      housed in a freestall barn with an AMS. Health problems were recorded, including
      subclinical ketosis (SCK; n = 19), metritis (n = 11), hoof disorders (n = 14),
      pneumonia (n = 7), and displaced abomasum (DA; n = 5). Data on rumination,
      activity, milking frequency and yield, and lying behavior were recorded
      electronically. Using repeated-measures mixed linear regression models, these
      data were analyzed for the days before the day of diagnosis/treatment (d 0) for
      each disorder separately, controlling for days in milk and parity. Analyses were
      performed between the day on which each outcome variable deviated significantly
      from baseline (up to d -14) and the day before diagnosis (nadir at d -1, before
      treatment and recovery). Outcomes tested were 3-d rolling averages of milk yield,
      milking frequency, and AMS supplement intake, in addition to daily rumination
      time (DRT), body weight, milk temperature, activity (measure of head/neck
      motion), and 3 lying behavior variables. From d -8, -6, and -5 before diagnosis
      of DA, SCK, or pneumonia, respectively, DRT declined by 45, 25, and 50 min/d.
      From d -14 to -1 before diagnosis of hoof disorders, DRT declined by 3 min/d.
      Body weight declined from d -4 before pneumonia (-14 kg/d) and metritis (-13
      kg/d), from d -6 before SCK (-10 kg/d), and from d -5 before hoof disorders (-5
      kg/d). Milk yield declined by 4.4 and 4.1 kg/d from d -4 before DA and pneumonia
      diagnoses, respectively, and by 1.2 kg/d from d -5 before SCK diagnosis. Activity
      levels declined before diagnosis of DA, pneumonia, SCK, or metritis. Lying
      behavior changed before diagnosis of DA, pneumonia, or metritis. Our results
      provide evidence that rumination behavior often deviated before milk yield and
      that several variables could contribute to earlier or automated identification of
      disorders. Behavior and productivity changed differently in association with
      various health disorders, suggesting the potential to distinguish among health
      problems. These variables merit further investigation in larger studies of cows
      milked with AMS.

PMID- 28755934
TI  - Fate of Listeria innocua during production and ripening of smeared hard cheese
      made from raw milk.
AB  - The fate of 2 different Listeria innocua strains was analyzed during the
      production and ripening of smeared raw milk Greyerzer cheese (Gruyere). These
      strains were used as surrogates for the pathogenic Listeria monocytogenes, as
      they are physiologically very similar. Bacterial cells were added to the cheese
      milk at levels of 105 cfu/mL. During the first 24 h of cheese making, the number
      of the test strains decreased to a level of below 102 cfu/g. Obviously, the
      cooking temperature of 56 degrees C and the subsequent slight temperature
      decrease to 50 degrees C within 70 min contributed to a distinct reduction of
      Listeria counts. The counts in the cheese cores did not exceed 103 cfu/g within
      12 wk of cheese ripening and Listeria was not detectable after 24 wk. In contrast
      to the cores of the cheeses of the 4 batches in this study, their rinds always
      contained a high listerial load of approximately 106 to 108 cfu/g throughout the
      entire ripening period. The smeared surface showed an increase of pH to alkaline
      values, corresponding to smear microbiota development. Coryneforms and
      Staphylococcus counts were stable at >107 cfu/cm2 over 175 d, whereas yeast
      counts decreased to about 105 cfu/cm2 at the end of ripening. The study shows
      that the smear culture had no noticeable anti-listerial potential. When removing
      the rind or portioning such smeared cheese loaves with a cutting device, a
      postprocess contamination of the core might occur, thus presenting a major
      hygienic risk.

PMID- 28755935
TI  - Effects of feeding pasteurized waste milk to dairy calves on phenotypes and
      genotypes of antimicrobial resistance in fecal Escherichia coli isolates before
      and after weaning.
AB  - The aim of this study was to evaluate the effects of feeding pasteurized waste
      milk (pWM) to calves on antimicrobial resistance of fecal Escherichia coli at
      both phenotypic and genotypic levels. Fifty-two Holstein female calves (3 +/- 1.3
      d of age) were fed 1 of the 2 different types of milk: milk replacer (MR) without
      antimicrobials or pWM with beta-lactam residues until weaning at 49 d of age.
      Fecal swabs of all calves were obtained on d 0, 35, and 56 of the study and 3 E.
      coli isolates per sample were studied. Phenotypic resistance was tested by the
      disk diffusion method against a panel of 12 antimicrobials. A total of 13
      resistance genes consisting of beta-lactam, sulfonamide, tetracycline, and
      aminoglycoside families were examined by PCR. Feeding pWM to calves increased the
      presence of phenotypic resistance to ampicillin, cephalotin, ceftiofur, and
      florfenicol in fecal E. coli compared with MR-fed calves. However, the presence
      of resistance to sulfonamides, tetracyclines, and aminoglycosides was common in
      dairy calves independent of their milk-feeding source, suggesting other factors
      apart from the feeding source are involved in the emergence of antimicrobial
      resistance.

PMID- 28755936
TI  - Short communication: Pseudomonas azotoformans causes gray discoloration in HTST
      fluid milk.
AB  - Pseudomonas species are well recognized as dairy product spoilage organisms,
      particularly due to their ability to grow at refrigeration temperatures. Although
      Pseudomonas-related spoilage usually manifests itself in flavor, odor, and
      texture defects, which are typically due to production of bacterial enzymes,
      Pseudomonas is also reported to cause color defects. Because of consumer
      complaints, a commercial dairy company shipped 4 samples of high temperature,
      short time (HTST)-pasteurized milk with distinctly gray colors to our laboratory.
      Bacterial isolates from all 4 samples were identified as Pseudomonas
      azotoformans. All isolates shared the same partial 16S rDNA sequence and showed
      black pigmentation on Dichloran Rose Bengal Chloramphenicol agar. Inoculation of
      one pigment-producing P. azotoformans isolate into HTST-pasteurized fluid milk
      led to development of gray milk after 14 d of storage at 6 degrees C, but only in
      containers that had half of the total volume filled with milk (~500 mL of milk in
      ~1,000-mL bottles). We conclusively demonstrate that Pseudomonas can cause a
      color defect in fluid milk that manifests in gray discoloration, adding to the
      palette of color defects known to be caused by Pseudomonas. This information is
      of considerable interest to the dairy industry, because dairy processors and
      others may not typically associate black or gray colors in fluid milk with the
      presence of microbial contaminants but rather with product tampering (e.g.,
      addition of ink) or other inadvertent chemical contamination.

PMID- 28755937
TI  - Lowering rumen-degradable protein maintained energy-corrected milk yield and
      improved nitrogen-use efficiency in multiparous lactating dairy cows exposed to
      heat stress.
AB  - The objective of this study was to examine the effect of reducing rumen
      degradable protein (RDP) and rumen-undegradable protein (RUP) proportions on feed
      intake, milk production, and N-use efficiency in primiparous and multiparous cows
      exposed to warm climates. Eighteen primiparous and 30 multiparous mid-lactation
      Holstein cows were used in a completely randomized design with a 2 * 2 factorial
      arrangement of treatments. Cows were randomly assigned to 1 of 4 dietary
      treatments formulated to contain 2 proportions of RDP (10 and 8%) and 2
      proportions RUP (8 and 6%) of dry matter (DM) indicated as follows: (1) 10% RDP,
      8% RUP; (2) 8% RDP, 8% RUP; (3) 10% RDP, 6% RUP; and (4) 8% RDP, 6% RUP. Protein
      sources were manipulated to obtain desired RDP and RUP proportions. Diets were
      isoenergetic and contained 50% forage and 50% concentrate (DM basis). Cows were
      individually fed the 10% RDP, 8% RUP diet 3 wk before treatment allocation. Cows
      were exposed to the prevailing Tennessee July and August temperature and humidity
      in a freestall barn with no supplemental cooling. Main effects and their
      interaction were tested using the Mixed procedure of SAS (least squares means +/-
      standard error of the mean; SAS Institute Inc., Cary, NC). Observed values of
      nutrient intake and milk production were used to obtain NRC (2001) model
      predictions. Cows showed signs of heat stress throughout the study. Reducing from
      10 to 8% RDP decreased dry matter intake (DMI; 0.9 kg/d) at 8% RUP, but increased
      DMI (2.6 kg/d) at 6% RUP in primiparous cows. Reducing from 10 to 8% RDP
      decreased milk yield (10%) at 8% RUP, but increased yield (14%) at 6% RUP.
      Treatments did not affect yield of energy-corrected milk. For multiparous cows,
      treatments did not affect DMI. Reducing from 10 to 8% RDP decreased yield of
      energy-corrected milk (3.4%) at 8% RUP, but increased yield (8.8%) at 6% RUP.
      Reducing from 10 to 8% RDP and 8 to 6% RUP both increased N-use efficiency for
      primiparous and multiparous cows. The NRC model underestimated metabolizable
      protein and RUP supply, and overestimated RUP requirements, resulting in
      predictive losses of milk yield 1.4 to 5.8 times greater than observed values. In
      summary, the reduction of RDP and RUP proportions did not affect DMI, whereas the
      RUP reduction at 10% RDP had a small negative effect on energy-corrected milk
      yield. However, reduction of RDP and RUP consistently improved N-use efficiency
      of heat-stressed multiparous cows. The reduction of RDP and RUP proportions
      reduced DMI and milk yield but did not affect energy-corrected milk yield in
      primiparous cows, indicating a limited supply of nutrients.

PMID- 28755938
TI  - Effects of photoperiod modulation and melatonin feeding around drying-off on
      bovine mammary gland involution.
AB  - The risk for a dairy cow to acquire new intramammary infections is high during
      the transition from lactation to the dry period, because of udder engorgement and
      altered immune functions. Once the gland is fully involuted, it becomes much more
      resistant to intramammary infections. Therefore, strategies to depress milk yield
      before drying-off and accelerate the involution process after drying-off could be
      beneficial for udder health. The objective of this study was to assess the effect
      of photoperiod manipulation and melatonin feeding from 14 d before to 14 d after
      drying-off on the speed of the involution process. Thirty Holstein cows in late
      lactation were randomly allocated to one of the following treatments: (1) a long
      day photoperiod (16 h of light: 8 h of darkness), (2) a short-day photoperiod (8
      h of light: 16 h of darkness), and (3) a long-day photoperiod supplemented by
      melatonin feeding (4 mg/kg of body weight). Milk and blood samples were collected
      on d -26, -19, -12, -5, -1, 1, 3, 5, 7, 10, and 14 relative to the last milking
      to determine concentrations of mammary gland involution markers and serum
      prolactin. Additional blood samples were taken around milking on d -15, before
      the start of the treatments, and on d -1, before drying-off, to evaluate the
      treatment effects on milking-induced prolactin release. The short-day photoperiod
      slightly decreased milk production and basal prolactin secretion during the dry
      period. The milking-induced prolactin surge was smaller on d -1 than on d -15
      regardless of the treatments. Lactoferrin concentration, somatic cell count, and
      BSA concentration as well as matrix metalloproteinase-2 and -9 activities
      increased in mammary secretions during the first 2 wk of the dry period, whereas
      milk citrate concentration and the citrate:lactoferrin molar ratio decreased. The
      rates of change of these parameters were not significantly affected by the
      treatments. The long-day photoperiod supplemented by melatonin feeding did not
      affect milk production, prolactin secretion, or mammary gland involution. Under
      the conditions in this study, photoperiod modulation and melatonin feeding did
      not appear to affect the rate of mammary gland involution.

PMID- 28755939
TI  - Multiplex PCR coupled with propidium monoazide for the detection of viable
      Cronobacter sakazakii, Bacillus cereus, and Salmonella spp. in milk and milk
      products.
AB  - Cronobacter sakazakii, Bacillus cereus, and Salmonella spp. are common food-borne
      pathogens. The aim of this study was to develop a sensitive, specific, and rapid
      method for the simultaneous detection of these 3 pathogens in milk and milk
      products. Three specific primers were designed based on ompA, invA, and cesB of
      C. sakazakii, Salmonella spp. and B. cereus, respectively, for use in a multiplex
      PCR (mPCR). To eliminate false-positive results, cells were pretreated with
      propidium monoazide (PMA) for the selective elimination of the genomic DNA of
      dead cells. An internal amplification control was applied as an indicator of
      false-negative results from the interference of inhibitors in the food matrix.
      Results showed that, in pure culture, the limits of detection of the assay for C.
      sakazakii, Salmonella Enteritidis, and B. cereus were 9.5 * 104, 7.4 * 102, and
      7.5 * 102 cfu/mL, respectively. Moreover, 8 cfu/mL of viable B. cereus cells were
      detected after 5 h of enrichment, and 9 cfu/mL of viable C. sakazakii and 7
      cfu/mL of Salmonella Enteritidis were detected after 7 h of enrichment in spiked
      pure milk, walnut peanut milk, and whole-wheat milk. To validate the PMA-mPCR
      assay, the PMA-mPCR assay and the traditional culture method were performed to
      detect the 3 bacterial strains in 1,165 milk product samples. The PMA-mPCR assay
      obtained the same results as the culture-based method. Results demonstrated that
      the PMA-mPCR assay has excellent sensitivity and specificity for the simultaneous
      detection of viable C. sakazakii, Salmonella Enteritidis, and B. cereus in milk
      and milk products.

PMID- 28755940
TI  - Behavioral and patho-physiological response as possible signs of pain in dairy
      cows during Escherichia coli mastitis: A pilot study.
AB  - Bovine mastitis is one of the most common diseases in the dairy industry and it
      is a major welfare problem. Pain during mastitis is generally assessed through
      behavior but a combination of indicators would increase the chances of detecting
      pain and assessing its intensity. The aim of this study was to assess behavioral
      and patho-physiological responses as possible signs of pain experienced by cows
      after experimental intramammary challenge (mastitis) with Escherichia coli. Six
      Holstein-Friesian cows received an inoculation of E. coli P4 in one healthy
      quarter. Evolution of the disease was assessed using bacteriological growth and
      somatic cell counts (SCC). Cows' response to the challenge was monitored by
      direct behavioral and clinical observations, data loggers, rumen temperature
      sensors, and indicators of inflammation, stress, and oxidative status. From all
      data recorded, the variables that contributed most to the discrimination of
      mastitis phases were obtained by factorial discriminant analysis. Baseline levels
      of all indicators corresponded to values before challenge. Specifically, we
      weighted data relating to lying behavior by the observations at the same hour of
      the day before challenge to eliminate the circadian rhythm effect. We identified
      3 phases that were discriminated by factorial discriminant analysis with good
      performance. Nine indicators varied according to the phase of the disease: cows'
      attitude toward their surroundings, tail position, clinical signs, ear position,
      variation of postural changes, concentrations of haptoglobin and serum amyloid A
      (SAA), cortisol blood levels, and rumen temperature (as a surrogate for body
      temperature). In phase 1 (4 to 8 h postinoculation), E. coli proliferated
      exponentially in milk but inflammation indicators remained at baseline levels.
      Cows were less attentive toward their surroundings (median score, 0.63), and
      postural changes (lying/standing) were less frequent (0.75 times from baseline).
      In phase 2 (12 to 24 h postinoculation), bacterial concentrations peaked around
      12 h and then began to decrease concomitantly with a sharp SCC increase. Cows
      were less attentive toward their surroundings (score, 0.54), had high plasma
      cortisol (31.3 ng/mL) and SAA (100.3 ug/mL) concentrations, and rumen temperature
      was increased (40.3 degrees C). In phase 3 (32 to 80 h postinoculation),
      bacterial concentrations decreased concomitantly with high SCC levels. Cows had
      high levels of haptoglobin (0.57 mg/mL) and SAA (269 ug/mL) but showed no
      behavioral changes. Dairy cows displayed changes of behavioral, inflammatory, and
      stress parameters after E. coli mammary inoculation. Our results suggest that
      cows may have experienced discomfort in the preclinical phase (phase 1) and pain
      in the acute phase (phase 2) but neither discomfort nor pain in the remission
      phase (phase 3). Although larger controlled studies are needed to confirm our
      findings, this knowledge could be useful for early detection of E. coli mastitis
      and for decision-making regarding the initiation of pain-relief treatment during
      mastitis in dairy cows. This would improve animal welfare and potentially faster
      disease remission.

PMID- 28755941
TI  - Technical note: Characterization of ceramide in bovine lipoproteins.
AB  - The hepatic synthesis and export of ceramide is enhanced in diabetic
      monogastrics. Moreover, ceramide in lipoproteins can mediate the development of
      insulin resistance. We have previously demonstrated that circulating ceramide
      increases during the progression of insulin resistance in postpartum dairy cows.
      Considering that the origins of circulating ceramide required investigation, our
      objective was to develop a method to characterize the ceramide profile of
      lipoprotein fractions collected from dairy cows. Serum was collected from 4
      nonpregnant and nonlactating Holstein dairy cows. Serum lipoproteins were
      isolated using size exclusion chromatography by fast protein liquid
      chromatography (SEC-FPLC). Measurement of triacylglycerol (TAG), phospholipid,
      total cholesterol, and protein was performed using standard colorimetry
      practices. Following lipid extraction, fractions were analyzed using electrospray
      ionization tandem mass spectrometry. Data were analyzed as repeated measures
      using a mixed model. Lipoprotein isolation using SEC-FPLC and subsequent
      colorimetric analyses confirmed the presence of 4 distinct fractions: TAG-rich,
      low density (LDL), and large (buoyant) and small (dense) high density lipoprotein
      (HDL) subclasses. As expected, the fraction representing mixed very low density
      lipoproteins and chylomicrons primarily contained TAG. Low density lipoprotein
      fractions were equally enriched with cholesterol and phospholipid. Buoyant HDL
      contained elevated levels of cholesterol, phospholipid, and protein. In contrast,
      the fraction containing dense HDL primarily contained protein. Our method
      revealed that LDL are enriched with ceramides. Ceramides were also
      compartmentalized to a lesser extent within both HDL subclasses and TAG-rich
      lipoproteins. Comparable to whole serum, C16:0-ceramide was the predominant
      ceramide quantified in all lipoprotein subclasses. Interestingly, the proportion
      of C24:0-ceramide to total ceramide was elevated in TAG-rich lipoproteins,
      relative to all other lipoprotein subclasses. We conclude that SEC-FPLC coupled
      with mass spectrometry is a means to quantify ceramides in lipoprotein fractions.
      Moreover, ceramides are enriched within bovine LDL, and lipoprotein ceramide
      profiles reflect levels observed in whole serum. Future investigation will need
      to determine the biological importance of lipoprotein ceramides with distinct C
      chains at amide residues.

PMID- 28755942
TI  - Regulation of inflammation, antioxidant production, and methyl-carbon metabolism
      during methionine supplementation in lipopolysaccharide-challenged neonatal
      bovine hepatocytes.
AB  - Supplementation of methionine (Met) may improve immunometabolic status,
      specifically during a period of inflammatory stress. The aim of the present study
      was to establish an inflammation model using primary neonatal bovine hepatocytes
      and to examine the effects of increasing concentrations of dl-Met and a
      maintained Met to lysine (Lys) ratio on hepatocyte inflammatory responses,
      antioxidant production, and Met metabolism during lipopolysaccharide (LPS)
      challenge. Hepatocytes isolated from 4 calves were maintained as monolayer
      cultures and exposed to 0, 10, or 40 uMdl-Met and 100 uM Lys (0Met100Lys,
      10Met100Lys, or 40Met100Lys) or 10 uMdl-Met and 25 uM Lys (10Met25Lys). Cells
      were exposed to each treatment for 16 h and then challenged with either 0 or 100
      ng/mL of LPS for 8 h. In the absence of LPS, glutathione (GSH) was not altered by
      10Met100Lys or 10Met25Lys but was increased by 40Met100Lys. With LPS challenge,
      GSH concentration was decreased with 40Met100Lys and tended to be decreased with
      10Met100Lys. Hepatocytes receiving 10Met100Lys treated with 100 ng/mL of LPS
      showed an inflammatory response with increased mRNA expression of tumor necrosis
      factor (TNFalpha), IL-6, IL-1beta, and interferon gamma, which was accompanied by
      increased nuclear factor kappaB inhibitor and serum amyloid A3 mRNA. The
      treatment 40Met100Lys was effective for preventing the LPS-induced increase in
      expression of the above genes except TNFalpha. Similar preventative effects were
      observed for 10Met25Lys; however, it did not prevent the LPS-induced increase in
      TNFalpha or IL-6 mRNA. Lipopolysaccharide challenge decreased mRNA expression of
      key genes controlling the transmethylation and Met regeneration pathways, which
      was not prevented by Met supplementation. The data suggest that bovine hepatocyte
      cultures can be used as a biological model to study the inflammatory cascade via
      an LPS challenge. Supplementation of Met prevents the LPS-induced hepatocyte
      cytokine expression and is associated with elevated intracellular GSH
      concentration.

PMID- 28755943
TI  - Feeding an enhanced diet to Holstein heifers during the preweaning period alters
      steroid receptor expression and increases cellular proliferation.
AB  - Preweaning diet and estradiol treatment alters mammary development. Our
      objectives were to study the effects of diet and estradiol on proliferation of
      mammary epithelial cells and expression of estrogen receptor alpha (ESR1) and
      progesterone receptors (PGR) in these cells. Thirty-six Holstein heifer calves
      were raised on (1) a control milk replacer fed at 0.44 kg of powder/head per day,
      dry matter (DM) basis (restricted, R; 20.9% crude protein, 19.8% fat, DM basis),
      or (2) an enhanced milk replacer fed at 1.08 kg of powder/head per day, DM basis
      (Enhanced, EH; 28.9% crude protein, 26.2% fat, DM basis). Milk replacer was fed
      for 8 wk. At weaning, a subset (n = 6/diet) of calves were euthanized and had
      tissue harvested. Remaining calves received estradiol implants (E2) or placebo
      and were euthanized at wk 10 to harvest tissue. Treatments were (1) R, (2) R + E2
      (R-E2), (3) EH, and (4) EH + E2 (EH-E2). One day before euthanasia calves were
      given bromo-2'-deoxyuridine (BrdU; 5 mg/kg of body weight). At euthanization,
      mammary parenchyma was removed and fixed. Tissue sections from zone 1
      (cisternal), 2 (medial), and 3 (distal) within the mammary gland were stained
      with hematoxylin and eosin and antibodies to measure expression of ESR1, PGR, and
      incorporation of BrdU. At wk 8, R-fed calves had more PGR-expressing cells in
      distal parenchyma; however, PGR expression intensity was greater in EH-fed
      calves. The proportion of cells expressing ESR1 was not affected by diet, but
      expression intensity (receptors per positive cell) was greater in EH-fed calves
      across all zones (62-81%). Overall, the percent BrdU-positive epithelial cells
      was 2 and 0.5 fold greater for EH-fed calves in zone 2 and 3. The proportion of
      labeled cells was greater in terminal ductal units than in subtending ducts, and
      treatment effects were more evident in terminal ductal units. At wk 10, calves
      treated with estradiol had 3.9-fold greater PGR expression intensity. The
      intensity and percent of cells expressing ESR1 was lowest in estradiol-treated
      calves. Overall, estradiol-treated calves had the greatest number of
      proliferating epithelial cells. Moreover, in zone 3, EH-E2 calves had a higher
      percentage of proliferating cells than in all other treatments. Results indicate
      both diet and estradiol administration alter proliferation rates of the mammary
      epithelium and that changes in expression of ESR1 and PGR are involved in
      enhanced mammary development. The data support our hypothesis that enhanced
      preweaning feeding increases the mammary tissue responsiveness to mammogenic
      stimulation.

PMID- 28755944
TI  - Health-promoting benefits of low-fat akawi cheese made by exopolysaccharide
      producing probiotic Lactobacillus plantarum isolated from camel milk.
AB  - Lactic acid bacteria isolated from camel milk exhibit remarkable probiotic and
      exopolysaccharide (EPS)-producing characteristics. The health-promoting benefits
      of exopolysaccharide-producing probiotic Lactobacillus plantarum isolated from
      camel milk used for making low-fat akawi cheese were investigated. Three low-fat
      akawi cheeses were made using traditional culture (non-EPS-producing, EPS-),
      commercial EPS-producing (MEPS+), and camel milk EPS-producing (CEPS+) cultures.
      alpha-Amylase and alpha-glucosidase inhibitory activities, antioxidant
      activities, angiotensin-converting enzyme (ACE) inhibition, and antiproliferative
      activity were determined. Cheese made with CEPS+ culture exhibited comparable
      alpha-amylase inhibition to that of cheeses made with MEPS+. Scavenging rates of
      cheese made with EPS+ cultures were higher than those of cheese made with EPS-
      cultures. The percentage of alpha-glucosidase inhibition ranged from >45% at 0 d
      to ~55% at 21 d of storage. After 7 d of storage, the scavenging rate in CEPS+
      cheese increased >60% by ABTS assay [2,2'-azino-bis(3-ethylbenzo-thiazoline-6
      sulfonic acid)] and >20% by DPPH assay (1,1-diphenyl-2-picrylhydrazyl).
      Throughout storage, cheese made with EPS+ cultures showed higher ACE-inhibition
      activity compared with EPS- cultures. Cheese made with CEPS+ showed ACE
      inhibition >70% after 7 d of storage. Antiproliferation activity of CEPS+ cheese
      increased from 38 to 48% during 7 d of storage and was maintained above 45% with
      prolonged storage. Low-fat akawi cheese produced with these cultures exhibited
      similar or greater health-promoting benefits compared with cheese made using
      commercial starter cultures. Therefore, incorporation of these cultures in food
      is promising for commercial uses.

PMID- 28755945
TI  - Standardization of milk mid-infrared spectrometers for the transfer and use of
      multiple models.
AB  - An increasing number of models are being developed to provide information from
      milk Fourier transform mid-infrared (FT-MIR) spectra on fine milk composition,
      technological properties of milk, or even cows' physiological status. In this
      context, and to take advantage of these existing models, the purpose of this work
      was to evaluate whether a spectral standardization method can enable the use of
      multiple equations within a network of different FT-MIR spectrometers. The
      piecewise direct standardization method was used, matching "slave" instruments to
      a common reference, the "master." The effect of standardization on network
      reproducibility was assessed on 66 instruments from 3 different brands by
      comparing the spectral variability of the slaves and the master with and without
      standardization. With standardization, the global Mahalanobis distance from the
      slave spectra to the master spectra was reduced on average from 2,655.9 to 14.3,
      representing a significant reduction of noninformative spectral variability. The
      transfer of models from instrument to instrument was tested using 3 FT-MIR models
      predicting (1) the quantity of daily methane emitted by dairy cows, (2) the
      concentration of polyunsaturated fatty acids in milk, and (3) the fresh cheese
      yield. The differences, in terms of root mean squared error, between master
      predictions and slave predictions were reduced after standardization on average
      from 103 to 17 g/d, from 0.0315 to 0.0045 g/100 mL of milk, and from 2.55 to 0.49
      g of curd/100 g of milk, respectively. For all the models, standard deviations of
      predictions among all the instruments were also reduced by 5.11 times for
      methane, 5.01 times for polyunsaturated fatty acids, and 7.05 times for fresh
      cheese yield, showing an improvement of prediction reproducibility within the
      network. Regarding the results obtained, spectral standardization allows the
      transfer and use of multiple models on all instruments as well as the improvement
      of spectral and prediction reproducibility within the network. The method makes
      the models universal, thereby offering opportunities for data exchange and the
      creation and use of common robust models at an international level to provide
      more information to the dairy sector from direct analysis of milk.

PMID- 28755946
TI  - Technical note: Evaluation of digital refractometers to estimate serum
      immunoglobulin G concentration and passive transfer in Jersey calves.
AB  - Previous data have demonstrated that refractometers can be used to estimate serum
      IgG, and that a cut-point of 7.8% Brix should be used to identify failure of
      passive transfer (FPT) in 1-d-old Holstein calves. The objective of the present
      study was to validate the use of refractometry to estimate serum IgG
      concentrations and evaluate FPT in Jersey calves. Blood samples (n = 97) were
      obtained from 1- to 3-d-old Jersey calves and centrifuged at 3,300 * g for 20 min
      at 25 degrees C. Serum was analyzed for % Brix, total protein (TP), and
      refractive index (nD) using a Sper Scientific Digital Refractometer (model
      #300036, Sper Scientific, Scottsdale, AZ) within 12 h of sampling. Samples were
      then frozen and later analyzed in the laboratory for IgG by radial
      immunodiffusion. The mean serum IgG concentration for all calves was 23.7 mg/mL
      (SD = 12.5), with a range of 2.3 to 65.5 mg/mL. Mean serum % Brix was 8.9 (SD =
      1.1; range 6.5 to 12.0). Serum % Brix was moderately correlated with IgG
      concentration (r = 0.77). Total protein and IgG were moderately correlated (r =
      0.790). Regression was used to determine cut-points for approximately 10, 12, and
      14 mg of IgG/mL and to determine the sensitivity and specificity of refractometry
      to identify FPT (serum IgG <10 mg/mL at 24 h of life). Brix cut-points analyzed
      were 7.1, 7.3, and 7.6%; TP cut-points were 4.6, 5.0, and 5.5 g/dL; and nD cut
      points were 1.34332, 1.34271, and 1.3448, respectively, for 10, 12, and 14 mg of
      IgG/mL. The 7.3% Brix and 4.6 g/dL TP cut-points resulted in the greatest
      percentage of samples being correctly classified. These data suggest that digital
      refractometry is an acceptable and rapid method to estimate immunoglobulin G in
      Jersey calf serum.

PMID- 28755947
TI  - Invited review: A systematic review and qualitative analysis of treatments other
      than conventional antimicrobials for clinical mastitis in dairy cows.
AB  - Clinical mastitis is an important disease in dairies. Its treatment is mainly
      based on the use of antimicrobial drugs. Numerous non-antimicrobial drugs and
      treatment strategies have already been reported for clinical mastitis treatment,
      but data on their efficacy have never been collated in a systematic way. The
      objective of this systematic review was to identify treatments other than
      conventional antimicrobials for the treatment of clinical mastitis in lactating
      dairy cows. A systematic review was performed with studies written in English or
      French selected from CAB Abstracts, PubMed, and Web of Science from January 1970
      to June 2014. Controlled clinical trials, observational studies, and experimental
      challenges were retained. Lactating dairy cows with clinical mastitis were the
      participant of interest. All treatments other than conventional antimicrobials
      for clinical mastitis during lactation were retained. Only studies comparing the
      treatment under investigation to a negative or positive control, or both, were
      included. Outcomes evaluated were clinical and bacteriological cure rates and
      milk production. Selection of the study, data extraction, and assessment of risk
      of bias was performed by 3 reviewers. Assessment of risk of bias was evaluated
      using the Cochrane Collaboration tool for systematic review of interventions. A
      total of 2,451 manuscripts were first identified and 39 manuscripts corresponding
      to 41 studies were included. Among these, 22 were clinical trials, 18 were
      experimental studies, and 1 was an observational study. The treatments evaluated
      were conventional anti-inflammatory drugs (n = 14), oxytocin with or without
      frequent milk out (n = 5), biologics (n = 9), homeopathy (n = 5), botanicals (n =
      4), probiotics (n = 2), and other alternative products (n = 2). All trials had at
      least one unclear or high risk of bias. Most trials (n = 13) did not observe
      significant differences in clinical or bacteriological cure rates in comparison
      with negative or positive controls. Few studies evaluated the effect of treatment
      on milk yield. In general, the power of the different studies was very low, thus
      precluding conclusions on noninferiority or nonsuperiority of the treatments
      investigated. No evidence-based recommendations could be given for the use of an
      alternative or non-antimicrobial conventional treatment for clinical mastitis.
      However, probiotics and oxytocin with or without frequent milk out should not be
      recommended. We concluded that homeopathic treatments are not efficient for
      management of clinical mastitis.

PMID- 28755948
TI  - Effect of tea saponins on milk performance, milk fatty acids, and immune function
      in dairy cow.
AB  - This study investigated the effects of tea saponins (TSP) on milk performance,
      milk fatty acids, and blood immune function in dairy cows. A total of 20 early
      lactation Holstein cows (days in milk = 66.4 +/- 16.8 d; parity = 1.75 +/- 0.91;
      and milk yield = 36.3 +/- 7.32 kg/d; mean +/- standard deviation) were randomly
      divided into 4 homogeneous treatment groups, with TSP added at 0, 20, 30, and 40
      g/d per head, respectively. All cows had 2 wk of adaptation and 6 wk of
      treatments. Feed, milk, and blood were sampled and analyzed weekly. At the end of
      the experimental period (wk 6), the dry matter intake and yields of energy
      corrected milk, milk, and milk protein, fat, and lactose in the cows fed TSP
      showed a quadratic response, with the lowest values in cows fed TSP at 40 g/d.
      The milk fat content of cows fed TSP increased linearly. Significant interactions
      for treatment by week were found in milk C16:1 cis-9 and C18:1 cis-9, with the
      highest values at wk 2, 3, and 4 in the cows fed TSP at 40 g/d. The levels
      declined quickly after 4 wk of feeding to values similar to those for other TSP
      treatments and the control at wk 5 and 6. Plasma malondialdehyde concentration
      decreased as the supplement level of TSP increased. The concentration of
      superoxide dismutase increased as the supplement level of TSP increased. The
      plasma concentration of tumor necrosis factor-alpha increased as the supplement
      level of TSP increased. In summary, this study showed that an intermediate dose
      of TSP (20 and 30 g/d) had no significant effect on feed intake, but the
      supplementation of 40 g/d TSP decreased feed intake, resulting in a lower milk
      yield. The energy-corrected milk of cows fed 40 g/d TSP declined at first but
      increased after 3 wk of feeding, indicating the potential adaptation to high
      doses of TSP supplements in dairy cows. The supplementation of TSP could reduce
      oxidative stress in cows and improve the immunity of dairy cows during 6 wk of
      feeding.

PMID- 28755949
TI  - Short communication: Passive shedding of Mycobacterium avium ssp.
      paratuberculosis in commercial dairy goats in Brazil.
AB  - Goat farming is a low-cost alternative to dairy production in developing
      countries. In Brazil, goat production has increased in recent years due in part
      to the implementation of programs encouraging this activity. Mycobacterium avium
      ssp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a disease
      that causes chronic granulomatous enteritis in ruminants, but MAP transmission
      dynamics are still poorly understood in goats. In a previously published study of
      our research group, 10 dairy goat farms (467 animals) from Minas Gerais state
      were analyzed for MAP detection; 2 fecal cultures and 11 milk samples tested
      positive for MAP by conventional PCR and were confirmed by sequencing. Because no
      clinical signs were observed over 1 yr of monitoring, we hypothesized that these
      MAP-positive goats could be passive shedders. Thus, in the present study, 4
      positive goats (4/13) from the previous study were purchased and feces and milk
      samples were collected for evaluation (twice, with an interval of 3 mo between
      tests) by culture of MAP, IS900 PCR, or both. All analyses were negative for MAP.
      At the last time point, blood samples were collected for ELISA, the animals were
      killed, and tissues collected for tissue culture and histopathology. At necropsy,
      no macroscopic lesions related to paratuberculosis were observed. Similarly, no
      histological changes were observed and MAP in samples stained by Ziehl-Neelsen
      was not detected. These animals were characterized as potential passive shedders
      with upward contamination of the teat canal by MAP. This is the first report of
      the passive shedding phenomenon in goats in Brazil and it highlights the
      importance of identifying these animals for control programs and to ensure the
      quality of dairy products.

PMID- 28755950
TI  - Priorities of biomedical research.

PMID- 28755951
TI  - Corrigendum to "Matrix metalloproteinase-9 (MMP-9) as an activator of nanosystems
      for targeted drug delivery in pancreatic cancer" [J. Control. Release 239 (2016)
      39-48].

PMID- 28755952
TI  - Are humans prone to autoimmunity? Implications from evolutionary changes in
      hominin sialic acid biology.
AB  - Given varied intrinsic and extrinsic challenges to the immune system, it is
      unsurprising that each evolutionary lineage evolves distinctive features of
      immunoreactivity, and that tolerance mechanisms fail, allowing autoimmunity.
      Humans appear prone to many autoimmune diseases, with mechanisms both genetic and
      environmental. Another rapidly evolving biological system involves sialic acids,
      a family of monosaccharides that are terminal caps on cell surface and secreted
      molecules of vertebrates, and play multifarious roles in immunity. We have
      explored multiple genomic changes in sialic acid biology that occurred in human
      ancestors (hominins), some with implications for enhanced immunoreactivity, and
      hence for autoimmunity. Human ancestors lost the enzyme synthesizing the common
      mammalian sialic acid Neu5Gc, with an accumulation of the precursor sialic acid
      Neu5Ac. Resulting changes include an enhanced reactivity by some immune cells and
      increased ability of macrophages to kill bacteria, at the cost of increased
      endotoxin sensitivity. There are also multiple human-specific evolutionary
      changes in inhibitory and activating Siglecs, immune cell receptors that
      recognize sialic acids as "self-associated molecular patterns" (SAMPs) to
      modulate immunity, but can also be hijacked by pathogen molecular mimicry of
      SAMPs. Altered expression patterns and fixed or polymorphic SIGLEC
      pseudogenization in humans has modulated both innate and adaptive immunity,
      sometimes favoring over-reactivity. Meanwhile, dietary intake of Neu5Gc (derived
      primarily from red meats) allows metabolic incorporation of this non-human
      molecule into human cells--apparently the first example of "xeno-autoimmunity"
      involving "xeno-autoantigen" interactions with circulating "xeno-autoantibodies".
      Taken together, some of these factors may contribute to the apparent human
      propensity for autoimmunity.

PMID- 28755953
TI  - Kidney toxicity related to herbs and dietary supplements: Online table of case
      reports. Part 3 of 5 series.
AB  - BACKGROUND: No tabular summary of potentially life-threatening, kidney-toxic
      dietary supplements (DS; includes herbs) based on PubMed case reports is
      currently available online and continually updated to forewarn United States
      consumers, clinicians, and companies manufacturing DS. The purpose of this review
      was to create an online research summary table of kidney toxicity case reports
      related to DS. METHODS: Documented PubMed case reports (1966 to May 2016, and
      cross-referencing) of DS appearing to contribute to kidney toxicity were listed
      in "DS Toxic Tables." Keywords included "herb" or "dietary supplement" combined
      with "kidney" to generate an overview list, and possibly "toxicity" to narrow the
      selection. Case reports were excluded if they involved herb combinations (some
      exceptions), Chinese herb mixtures, teas of mixed herb contents, mushrooms,
      poisonous plants, self-harm, excessive doses (except vitamins/minerals), legal or
      illegal drugs, drug-herbal interactions, and confounders of drugs or diseases.
      Since commercial DS often include a combination of ingredients, they were treated
      separately; so were foods. A few foods with kidney-toxic effects were listed in a
      fourth table. The spectrum of herbal or DS-induced kidney injuries included
      kidney stones, nephritis, nephrotic syndrome, necrosis, acute kidney injury (AKI;
      previously known as acute renal failure [ARF]), chronic kidney disease, kidney
      transplant, and death. RESULTS: Approximately 7 herbs (minus 4 no longer for
      sale) and 10 dietary supplements (minus 3 excluded due to excessive doses +
      germanium that is no longer sold) have been related to kidney injury case reports
      published in PubMed (+crosslisting) in the last 50 + years (1966 to May 2016).
      The implicated herbs include Chinese yew (Taxus celbica) extract, impila
      (Callilepis laureola), morning cypress (Cupressus funebris Endl), St. John's wort
      (Hypericum perforatum), thundergod vine (Tripterygium wilfordii hook F), tribulus
      (Tribulus terrestris) and wormwood (Artemisia herba-alba). No longer sold in the
      United States are chocolate vine or mu tong (Caulis aristolochiae), guang fang ji
      (Aristolochia fangchi), ma huang (Ephedra sinica), and Tenshin Tokishigyaku-ka
      goshuyu-shokyo-to. The DS include bile (sheep), chlorella, chromium (Cr), CKLS,
      creatine, gallbladder (fish), glucosamine, hydrazine, N.O.-Xplode, Spanish fly,
      and excess intakes of vitamins A, C, and D. Germanium (Ge) is not available for
      sale. The top two DS with the largest number of reported publications, but not
      always case reports, in descending order, were the aristolochic acid-containing
      herbs guang fang ji (mistaken identity) and chocolate vine or mu tong. The
      remaining DS featured one to three publications over a 50+ year period. Numerous
      case reports were reported for kidney-toxic foods: djenkol bean, gallbladders
      (carp fish, pufferfish, & snake), and star fruit (only in chronic kidney disease
      patients), and uncooked yam powder or juice. CONCLUSION: This online "DS Toxic
      Table" provides clinicians, consumers, and manufacturers with a list of herbs
      that could potentially contribute to kidney injuries.

PMID- 28755954
TI  - Duality between cooperation and defection in the presence of tit-for-tat in
      replicator dynamics.
AB  - The prisoner's dilemma describes a conflict between a pair of players, in which
      defection is a dominant strategy whereas cooperation is collectively optimal. The
      iterated version of the dilemma has been extensively studied to understand the
      emergence of cooperation. In the evolutionary context, the iterated prisoner's
      dilemma is often combined with population dynamics, in which a more successful
      strategy replicates itself with a higher growth rate. Here, we investigate the
      replicator dynamics of three representative strategies, i.e., unconditional
      cooperation, unconditional defection, and tit-for-tat, which prescribes
      reciprocal cooperation by mimicking the opponent's previous move. Our finding is
      that the dynamics is self-dual in the sense that it remains invariant when we
      apply time reversal and exchange the fractions of unconditional cooperators and
      defectors in the population. The duality implies that the fractions can be
      equalized by tit-for-tat players, although unconditional cooperation is still
      dominated by defection. Furthermore, we find that mutation among the strategies
      breaks the exact duality in such a way that cooperation is more favored than
      defection, as long as the cost-to-benefit ratio of cooperation is small.

PMID- 28755955
TI  - Hill equation and Hatze's muscle activation dynamics complement each other:
      enhanced pharmacological and physiological interpretability of modelled activity
      pCa curves.
AB  - In pharmacology, particularly receptor theory, the drug dose-effect relation of
      bio-active substances is frequently described by a sigmoidal function formulated
      by A.V. Hill. In biomechanics and muscle physiology then again, H. Hatze had
      elaborated a mathematical model for the stimulation- and length-dependent
      dynamics of the calcium-induced activation of mammalian skeletal muscle. Here, we
      prove that muscular activity-pCa curves described by the Hill equation and the
      equilibrium state predicted by Hatze's activation dynamics are equivalent. Thus,
      the exponent introduced by Hatze can be directly identified with its counterpart
      in the Hill equation, by which the former model gains further physiological
      interpretability. Conversely, the Hill constant can now be interpreted as a
      function of the fibre length, generally allowing for advanced Hill plots based on
      model ideas. We derive and examine the complementary relation of both model
      approaches, highlight the benefits of mutually viewing one approach from the
      perspective of the other, and address the physiology behind sigmoidal curves.

PMID- 28755956
TI  - A note on stress-driven anisotropic diffusion and its role in active deformable
      media.
AB  - We introduce a new model to describe diffusion processes within active deformable
      media. Our general theoretical framework is based on physical and mathematical
      considerations, and it suggests to employ diffusion tensors directly influenced
      by the coupling with mechanical stress. The proposed generalised reaction
      diffusion-mechanics model reveals that initially isotropic and homogeneous
      diffusion tensors turn into inhomogeneous and anisotropic quantities due to the
      intrinsic structure of the nonlinear coupling. We study the physical properties
      leading to these effects, and investigate mathematical conditions for its
      occurrence. Together, the mathematical model and the numerical results obtained
      using a mixed-primal finite element method, clearly support relevant consequences
      of stress-driven diffusion into anisotropy patterns, drifting, and conduction
      velocity of the resulting excitation waves. Our findings also indicate the
      applicability of this novel approach in the description of mechano-electric
      feedback in actively deforming bio-materials such as the cardiac tissue.

PMID- 28755957
TI  - Semblance of Heterogeneity in Collective Cell Migration.
AB  - Cell population heterogeneity is increasingly a focus of inquiry in biological
      research. For example, cell migration studies have investigated the heterogeneity
      of invasiveness and taxis in development, wound healing, and cancer. However,
      relatively little effort has been devoted to exploring when heterogeneity is
      mechanistically relevant and how to reliably measure it. Statistical methods from
      the animal movement literature offer the potential to analyze heterogeneity in
      collections of cell tracking data. A popular measure of heterogeneity, which we
      use here as an example, is the distribution of delays in directional cross
      correlation. Employing a suitably generic, yet minimal, model of collective cell
      movement in three dimensions, we show how using such measures to quantify
      heterogeneity in tracking data can result in the inference of heterogeneity where
      there is none. Our study highlights a potential pitfall in the statistical
      analysis of cell population heterogeneity, and we argue that this can be
      mitigated by the appropriate choice of null models.

PMID- 28755958
TI  - Why Do Fast-Growing Bacteria Enter Overflow Metabolism? Testing the Membrane Real
      Estate Hypothesis.
AB  - Bacteria and other cells show a puzzling behavior. At high growth rates, E. coli
      switch from respiration (which is ATP-efficient) to using fermentation for
      additional ATP (which is inefficient). This overflow metabolism results in a
      several-fold decrease in ATP produced per glucose molecule provided as food. By
      integrating diverse types of experimental data into a simple biophysical model,
      we give evidence that this onset is the result of the membrane real estate
      hypothesis: Fast growth drives cells to be bigger, reducing their surface-to
      volume ratios. This decreases the membrane area available for respiratory
      proteins despite growing demand, causing increased crowding. Only when
      respiratory proteins reach their crowding limit does the cell activate
      fermentation, since fermentation allows faster ATP production per unit membrane
      area. Surface limitation thus creates a Pareto trade-off between membrane
      efficiency and ATP yield that links metabolic choice to the size and shape of a
      bacterial cell. By exploring the predictions that emerge from this trade-off, we
      show how consideration of molecular structures, energetics, rates, and equilibria
      can provide important insight into cellular behavior.

PMID- 28755959
TI  - An open label, single-arm, phase II multicenter study of the safety and efficacy
      of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle
      invasive bladder cancer: Interim results.
AB  - OBJECTIVES: CG0070 is a replication-competent oncolytic adenovirus that targets
      bladder tumor cells through their defective retinoblastoma pathway. Prior reports
      of intravesical CG0070 have shown promising activity in patients with high-grade
      non-muscle invasive bladder cancer (NMIBC) who previously did not respond to
      bacillus Calmette-Guerin (BCG). However, limited accrual has hindered analysis of
      efficacy, particularly for pathologic subsets. We evaluated interim results of a
      phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC
      who refused cystectomy. PATIENTS AND METHODS: At interim analysis (April 2017),
      45 patients with residual high-grade Ta, T1, or carcinoma-in-situ (CIS) +/- Ta/T1
      had evaluable 6-month follow-up in this phase II single-arm multicenter trial
      (NCT02365818). All patients received at least 2 prior courses of intravesical
      therapy for CIS, with at least 1 being a course of BCG. Patients had either
      failed BCG induction therapy within 6 months or had been successfully treated
      with BCG with subsequent recurrence. Complete response (CR) at 6 months was
      defined as absence of disease on cytology, cystoscopy, and random biopsies.
      RESULTS: Of 45 patients, there were 24 pure CIS, 8 CIS + Ta, 4 CIS + T1, 6 Ta, 3
      T1. Overall 6-month CR (95% CI) was 47% (32%-62%). Considering 6-month CR for
      pathologic subsets, pure CIS was 58% (37%-78%), CIS +/- Ta/T1 50% (33%-67%), and
      pure Ta/T1 33% (8%-70%). At 6 months, the single patient that progressed to
      muscle-invasive disease had Ta and T1 tumors at baseline. No patients with pure
      T1 had 6-month CR. Treatment-related adverse events (AEs) at 6 months were most
      commonly urinary bladder spasms (36%), hematuria (28%), dysuria (25%), and
      urgency (22%). Immunologic treatment-related AEs included flu-like symptoms (12%)
      and fatigue (6%). Grade III treatment-related AEs included dysuria (3%) and
      hypotension (1.5%). There were no Grade IV/V treatment-related AEs. CONCLUSIONS:
      This phase II study demonstrates that intravesical CG0070 yielded an overall 47%
      CR rate at 6 months for all patients and 50% for patients with CIS, with an
      acceptable level of toxicity for patients with high-risk BCG-unresponsive NMIBC.
      There is a particularly strong response and limited progression in patients with
      pure CIS.

PMID- 28755960
TI  - Hospitalization before surgery and subsequent risk of infective complications
      after radical cystectomy: A population-based analysis.
AB  - INTRODUCTION: The length of stay prior to surgery increases the risk of
      postoperative infections (PIs) in several surgical settings, such as cardiac,
      orthopedic, and general surgery. However, data for urological oncology procedures
      are limited. We examined PI rates after radical cystectomy (RC) according to the
      length of stay prior to RC (LOSPRC). MATERIALS AND METHODS: A total of 24,242
      patients with bladder cancer treated with RC between 1998 and 2013 were
      abstracted from the National Inpatients Sample database. We evaluated changes
      over time in LOSPRC (0 vs. 1 vs. 2 days or more) and tested its effect on PI
      rates. Multivariable logistic regression analyses were adjusted for the year of
      surgery, sex, age, ethnicity, comorbidities, hospital location, teaching status,
      hospital surgical volume, and number of hospital beds. RESULTS: Overall, 19,401
      (80.0%), 3,990 (16.5%), and 851 (3.5%) individuals with LOSPRC of 0, 1. and 2 or
      more were identified. The proportion of LOSPRC 0 patients increased from 61.4% in
      1998 to 91.0% in 2013 (P<0.001), whereas the opposite trend was observed for
      LOSPRC 1 and 2 or more. In multivariable logistic regression analyses predicting
      PIs, LOSPRC of 1 (odds ratio: 1.38; 95% CI: 1.25-1.53; P<0.001) and LOSPRC of 2
      or more (odds ratio: 2.15; 95% CI: 1.81-2.55; P<0.001) achieved independent
      predictor status. CONCLUSIONS: A delay in surgery as short as 1 day significantly
      increases the risk of PIs after RC. In consequence, same day of admission surgery
      policies should be further promoted to reduce the risk of PIs.

PMID- 28755961
TI  - Patient engagement in the design and execution of urologic oncology research.
AB  - INTRODUCTION: There have been significant effort and financial support to engage
      patients in the design and execution of medical research. However, little is
      known about the relative benefits or potential impact of involving patients in
      research, most efficient practices and systems to enhance their involvement, and
      potential barriers and challenges that are involved with engaging patients. In
      this review, we will discuss the value of patient centered research, review the
      challenges that many of these studies faced, and highlight potential future
      opportunities to enhance patient involvement in urologic research. METHODS: An
      English-language literature search was performed in the electronic databases of
      Medline (PubMed), EMBASE, Web of Science, Google Scholar, the Cochrane Library,
      and on the Patient Centered Outcomes Research Institute (PCORI) website. Search
      items included "patient-centered research," "patient-reported outcomes" and
      "patient engagement" in various combinations. Although PCORI has funded almost
      600 projects with $1.6 billion to improve patient centered research, the search
      revealed 3 studies of patient engagement in the development, management, and
      execution of urologic oncology research. RESULTS: Patient engagement in the
      design and execution of medical research can help align research topics to match
      patient priorities, improve survey and data collection tools, increase patient
      recruitment and participation in studies, and improve accessibility and
      dissemination of clinically relevant results from medical research. However,
      engagement patients in research requires significant investment of time,
      financial support, and energy from the patients, stakeholders, and researchers to
      provide mutual benefit. In the three studies in urologic oncology that involved
      patients, the patients provided a significant impact on the structure of the
      studies and helped improve the ability of patients to apply the results from the
      research studies. CONCLUSIONS: The benefits to involving patients in research to
      improve the access, understanding, and application of clinical evidence can be
      significant. Patient engagement in urologic oncology research is limited
      currently, but is expected to grow as the funding agencies incentivize the
      practice and the culture shifts toward a greater emphasis on patient centered
      outcomes.

PMID- 28755962
TI  - Are the Cavernous Tissue and Serum Levels of Micro RNAs 200a and 206 Elevated in
      Patients With Refractory Veno-occlusive Erectile Dysfunction? A Comparative
      Study.
AB  - OBJECTIVE: To evaluate the association between miRNAs and veno-occlusive erectile
      dysfunction. Recently, this association between miRNAs and erectile dysfunction
      was extensively studied using animal models. Our aim was to explore the miRNAs
      expressions and functions in the development of erectile dysfunction, especially
      veno-occlusive dysfunction, using a human tissue. PATIENTS AND METHODS: We
      prospectively recruited 60 patients with erectile dysfunction and controls
      between July 2015 and July 2016. The 30 patients had refractory veno-occlusive
      erectile dysfunction that was proven by investigations. They were scheduled for
      penile implant. The 30 controls were scheduled for repair of their fracture. We
      measured miRNAs (200a and 206) and nitric oxide in cavernous tissue and serum of
      both patients with erectile dysfunction and controls. RESULTS: A significant
      association was found between the 2 mentioned miRNAs and erectile dysfunction (P
      <.001). Mean level of nitric oxide in cavernous tissue of the controls was
      significantly higher than that in the patients (P <.001). miRNA 200a showed a
      cutoff value of 1.135 with 95% sensitivity and 100% specificity, whereas miRNA
      206 showed a cutoff value of 1.125 with 100% sensitivity and 100% specificity.
      CONCLUSION: To the best of our knowledge, our study is the first report to
      measure the level of miRNAs in the cavernous tissue, using a human tissue.
      Furthermore, this study can be considered a good step of deploying miRNAs through
      a blood test to detect early negative changes that lead to erectile dysfunction.
      Finally, we recommend more studies to be conducted to better understand if these
      miRNAs are involved in the pathophysiology of veno-occlusive erectile
      dysfunction.

PMID- 28755963
TI  - Re: Yoshida et al.: Ureteral Wall Thickness as a Preoperative Indicator of
      Impacted Stones in Patients With Ureteral Stones Undergoing Ureteroscopic
      Lithotripsy (Urology 2017;106:45-49).

PMID- 28755964
TI  - Emergency Department Utilization in Patients With Neurogenic Bladder:
      Contemporary Burden and National Trends in Prevalence, Inpatient Admission, and
      Associated Charges, 2006-2011.
AB  - OBJECTIVE: To quantify the national burden of neurogenic bladder disease, a
      chronic debilitating condition associated with frequent hospital visits, in the
      contemporary emergency care setting. METHODS: Relying on the Nationwide Emergency
      Department Sample, 2006-2011, we abstracted patients presenting to the emergency
      department (ED) with neurogenic bladder utilizing International Classification of
      Diseases, Ninth Revision (ICD-9) codes. National trends in ED presentation,
      subsequent inpatient admission vs discharge, and associated charges were examined
      using the estimated annual percent change methodology. RESULTS: Over the study
      period, a total of 875,066 patients with neurogenic bladder were seen in the ED,
      of which 538,532 (61.5%) were admitted. Total and median ED charges increased at
      an annual rate of 36.66% (P <.001) and 13.24% (P <.001), respectively, with total
      ED charges amounting to 87.48 million USD in the year 2011. Annual ED utilization
      also increased, although at a slower rate, 1.89% (P = .017). Inpatient admissions
      decreased at an annual rate of 3.67% (P <.001), whereas the use of long-term care
      facilities increased at 11.82% (P = .005). CONCLUSION: Total ED charges are
      increasing at a dramatic rate, driven by the increasing utilization of the ED as
      an entry point to health care as well as the increasing per-visit charges.
      Encouragingly, the rates of inpatient admission are decreasing, likely secondary
      to improved triaging in the ED and increased utilization of long-term care
      facilities. It remains to be seen, however, whether the increased spending in the
      ED for better triaging and investment in long-term care facilities will translate
      into an overall economic benefit by reducing inpatient charges or not.

PMID- 28755965
TI  - WITHDRAWN: Author Reply to the Editorial Comment on: Zacho HD, Gade M, Mortensen
      JC, Bertelsen H, Boldsen SK, Petersen LJ. Bone Scan Index Is an Independent
      Predictor for Time to Castration Resistant Prostate Cancer in Newly Diagnosed
      Prostate Cancer: A Prospective Study. Urology 2017, In Press.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.urology.2017.05.060. The duplicate article has
      therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be
      found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

PMID- 28755966
TI  - Characteristics of Idiopathic Urethral Strictures: A Link to Remote Perineal
      Trauma?
AB  - OBJECTIVE: To characterize the physical features and reconstructive outcomes of a
      series of idiopathic urethral strictures (IUS) in an effort to elucidate the
      nature of this common yet poorly understood entity. PATIENTS AND METHODS: We
      retrospectively reviewed our urethroplasty database to identify men undergoing
      initial urethral reconstruction from 2007 to 2014 at 1 of 3 hospitals (N = 514).
      Patients were stratified by stricture etiology, including IUS, acute trauma,
      iatrogenic, hypospadias, balanitis xerotica obliterans, and radiation. IUS that
      had a known history of subacute or repetitive blunt force to the perineum
      (horseback riding, avid cycling, motocross, etc.) were subclassified as subacute
      or repetitive perineal trauma (SRPT). RESULTS: Among 466 men undergoing initial
      reconstruction with available data, 215 (46%) were IUS cases. The median delay
      between IUS diagnosis and urethroplasty was 5.2 years, during which time men
      underwent a median of 2 endoscopic treatments. A total of 51 (24%) IUS cases
      recalled a distinct history of SRPT. Men with SRPT were slightly younger (median
      43 vs 48 years, P = .01) but were remarkably similar in terms of urethral
      stricture length (2 vs 2 cm, P = .15), location (bulbar 96% vs 89%, P = .41), and
      treatment success (92% vs 88%; P = .61). Bulbar (-)SRPT and (+)SRPT IUS had
      similar clinical and morphometric features as those with known acute bulbar
      trauma with excellent 24-month stricture recurrence-free survival rates (93% vs
      92% vs 97%, P = .19). CONCLUSION: IUS have clinical features suggesting that many
      may be related to unrecognized or repetitive perineal trauma. Although treatment
      tends to be delayed, IUS have excellent urethroplasty success because most are
      short bulbar strictures amenable to anastomotic urethroplasty.

PMID- 28755967
TI  - Emergency department visits and readmissions within 1 year of bariatric surgery:
      A statewide analysis using hospital discharge records.
AB  - BACKGROUND: Data are limited regarding emergency department visits and
      readmission rates beyond 30 days after bariatric surgery. We analyzed emergency
      department visits and readmissions to all facilities in Wisconsin within 1 year
      of bariatric surgery and identified their predictors. METHODS: All adults who
      underwent a laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy from 2011
      2014 were identified. Bivariate associations between patient/hospital factors and
      emergency department visits/readmissions were examined, and factors significant
      at P < .1 were included in multivariable logistic regression models. RESULTS:
      Within 1 year of bariatric surgery, 36.9% of emergency department visits and
      60.3% of readmissions were to the same institution in which bariatric surgery was
      performed. The frequency of emergency department visits ranged from 10.7%
      (postoperative days 0-30) to 5.7% (postoperative days 181-270). Readmission rates
      ranged from 4.4% (postoperative days 0-30) to 2.7% (postoperative days 91-180).
      Readmission within 1 year was associated with male sex, Roux-en-Y gastric bypass,
      >=4 comorbidities, Medicare insurance, teaching hospitals, and inpatient
      complications (all P < .05). CONCLUSION: Emergency department visits and
      readmissions persist throughout the first year at a relatively steady rate after
      30 days and often do not occur where bariatric surgery was performed. Quality
      improvement efforts targeting these patients may improve outcomes and decrease
      hospital resource utilization.

PMID- 28755968
TI  - Surgical and medical approach to patients requiring total small bowel resection:
      Managing the "no gut syndrome".
AB  - BACKGROUND: Total resection of the jejunum and ileum, a rarely performed
      procedure, is indicated after mesenteric vascular events, trauma, or resection of
      abdominal neoplasms. We describe our recent experience with the operative and
      medical management of patients with "no gut syndrome." METHODS: We
      retrospectively reviewed 341 adult patients who were referred to our center
      between January 2013 and December 2016. RESULTS: Thirteen patients with a mean
      age of 42.5 years (range 17 to 66 years) underwent near total enterectomy.
      Indications for small bowel resection were vascular event (n = 5), intraabdominal
      fibroid/desmoid (n = 4), and trauma (n = 4). Foregut secretions were managed with
      duodenocolostomy (n = 5), tube decompression (n = 5), and end duodenostomy (n =
      2). Duodenal stump was stapled off in 4 cases. One patient underwent a spleen
      preserving duodenopancreatectomy combined with total enterectomy. Biliary
      secretions were managed with choledochocolostomy. All patients were discharged on
      full total parenteral nutrition infused over a 10- to 16-hour period. Average
      total parenteral nutrition volume and caloric requirement were 2,800 mL/day
      (range 2,000 to 4,000) and 1,774 Kcal/day (range 1,443 to 2,290), respectively.
      Patients who underwent duodenocolonic anastomosis received smaller TPN volume
      (33.8 vs 49.8 mL/kg). Ten patients (77%) required supplemental intravenous fluid.
      There were no intraoperative or perioperative deaths. One patient was lost to
      follow-up 2 months after operation. After a 20-month median follow-up (range 4 to
      48 months), 9 patients are still alive (75%). All patients with duodenocolostomy
      remain alive (median follow-up 36.4 months). Three patients underwent uneventful
      isolated small bowel transplantation, and another 4 are being evaluated or are
      already listed for visceral transplantation. CONCLUSION: In summary, resection of
      the entire small bowel is feasible and can be a lifesaving procedure for a select
      group of patients. Long-term survival can be achieved in specialized centers. In
      addition, reestablishment of gastrointestinal tract continuity after total
      enterectomy appears to be the best option for postoperative fluid and electrolyte
      management.

PMID- 28755969
TI  - Plant-based remedies for wolf bites and rituals against wolves in the Iberian
      Peninsula: Therapeutic opportunities and cultural values for the conservation of
      biocultural diversity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Combined approaches to local knowledge and folk
      plant use improve awareness and promote effective strategies for the conservation
      of significant biocultural patrimony. Moreover, the information reported might be
      the basis for further appropriate phytochemical and pharmacological research.
      Therefore we provide an insight into traditional herbal remedies and practices
      for healing bite injuries in humans and domestic animals caused by the Iberian
      wolf. Wolf bites are associated with inflammatory processes and rabies is a
      potential complication AIMS: This paper describes and summarises the medicinal
      veterinary empirical and ritual uses of the Iberian flora for wolf injuries and
      reviews the ethnopharmacological data of specific plants that are already
      published. The Iberian wolf is a critically endangered subspecies of the grey
      wolf. Livestock attacks attributed to wolves are increasingly frequent in the
      Iberian Peninsula, resulting in serious social problems. Interesting strategies
      for Iberian wolf conservation might be related to traditional grazing practices
      that are deeply linked with empirical knowledge and local practices passed on by
      oral tradition, which are also vulnerable now. MATERIALS AND METHODS: Based on
      documentary sources from the beginning of the twentieth century to the present,
      we systematically searched old monographs, regional documents, technical papers,
      project reports, as well as the international and national databases and the
      available scientific literature, without restrictions regarding the language of
      the publications consulted. RESULTS: A total of 39 remedies for healing wolf bite
      injuries in humans and domestic animals was reported, highlighting the medicinal
      use of 33 species of vascular plants, mostly wild herbs, belonging to 18
      botanical families. The use of wood ashes was also reported. The number of use
      reports found represents a very high number considering similar European studies.
      Leaves were the predominant plant part mentioned. Boiling plant materials in
      water for topical uses was the most frequent method of preparation found. Some
      traditional remedies combined two or more plant species in order to potentiate
      their effects. Moreover, some plant-based traditional practices and rituals to
      ward off wolves and to prevent wolf attacks were also documented. In these
      practices eleven other species (belonging to seven more families) were used.
      CONCLUSIONS: Despite the decline of the Iberian wolf over the last few decades,
      wolves are still in the imaginary of rural communities that perceive this large
      carnivore as both a diabolic creature and a mythic and benign animal. Wolf
      related cultural heritage is of great interest in terms of conservation
      strategies. This review emphasises the importance of local knowledge and provides
      useful information about several potential sources of phytochemicals and their
      claimed therapeutic effects, aiming at contributing to the conservation and
      appreciation of the Iberian biocultural heritage.

PMID- 28755970
TI  - Differences of first-pass effect in the liver and intestine contribute to the
      stereoselective pharmacokinetics of rhynchophylline and isorhynchophylline
      epimers in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (Miq.) Miq. ex Havil., is a
      plant species used in traditional Chinese medicine to treat cardiovascular and
      central nervous system diseases. Rhynchophylline (RIN) and isorhynchophylline
      (IRN), a pair of epimers, are major alkaloids isolated from U. rhynchophylla and
      exhibit diverse pharmacological effects. Our previous study demonstrated that the
      pharmacokinetics of these epimers existed stereoselectivity after oral
      administration; however, the specific mechanism remains unknown and merits
      investigation. AIM OF THE STUDY: In the present study, the aim was to elucidate
      the mechanism underlying stereoselective pharmacokinetic characteristics of RIN
      and IRN in rats. MATERIALS AND METHODS: The total (F), hepatic (Fh) and
      intestinal (Fa.Fg) bioavailabilities of each epimer were measured using portal
      vein cannulated rats following different dosing routes (intravenous, intraportal
      and intraduodenal) to assess individual contributions of the liver and intestine
      in stereoselective pharmacokinetics. Then the differences of first-pass
      metabolism in the liver and intestine between two epimers were evaluated by in
      vitro incubation with rat liver microsomes, intestinal S9 and gastrointestinal
      (GI) content solutions, respectively. Meanwhile, the membrane permeability and
      efflux by P-glycoprotein (P-gp) were examined by in situ single-pass intestinal
      perfusion with and without P-gp inhibitor verapamil. The configurational
      interconversion at different pH values and the excretions via feces and urine
      were also examined. RESULTS: Pharmacokinetic data showed that the total
      bioavailability of RIN was 5.9 folds higher than that of IRN (23.4% vs. 4.0%).
      The hepatic availability of RIN was 4.6 folds higher than that of IRN (46.9% vs.
      10.3%), whereas the intestinal availability of RIN (48.1%) was comparable to that
      of IRN (42.7%). In addition, intestinal perfusion showed that IRN possessed
      higher intestinal permeability than RIN and co-perfusion with verapamil could
      affect absorption process of RIN but not IRN. Conversely, the metabolism rate of
      IRN in rat liver microsomes was significantly faster than that of RIN, resulting
      in a lower systemic exposure of IRN after oral administration. The degradation in
      GI lumen and epimerization between two epimers also existed but had small
      contributions. Additionally, the excretions of both epimers via feces and urine
      were negligible. CONCLUSIONS: Taken together, different first-pass metabolism in
      the liver was the major factor responsible for the stereoselective
      pharmacokinetics of RIN and IRN.

PMID- 28755971
TI  - Efficacy of standardized extract of Hibiscus sabdariffa L. (Malvaceae) in
      improving iron status of adults in malaria endemic area: A randomized controlled
      trial.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Indigenous community of Mkuranga district have
      been using aqueous extract of H. sabdariffa L. for treating anemia. However,
      there have been neither safety nor efficacy studies to validate this medicinal
      product in anemia. AIM: The purpose of this study was to establish efficacy and
      safety of standardized aqueous extract of H. sabdariffa L. in anemic adults.
      MATERIALS AND METHODS: This was a randomized controlled clinical trial in which
      130 adults' men and women aged 18-50 years were involved after meeting the
      inclusion criteria. Initially, standardized aqueous extract of H. sabdariffa L.
      was prepared using optimized extraction parameters. Stratified randomization was
      used to randomize participants into four fixed dose groups. The first group
      received oral dose of 1000ml while the 2nd group was randomized to receive 1500ml
      orally. The last two groups were given a dose of 2000ml of extract and 200mg
      ferrous sulphate tablet respectively. Primary endpoint was the actual change of
      iron status indicators at the end of 30 days follow up period as compared to
      those recorded at baseline. Adverse effects were assessed at every 10th day
      scheduled visit. In all arms, HB and hematopoietic parameters were measured using
      HemoCue hemoglobinometer(r) (HemoCue, Angelholm, Sweden) and hematology
      analyzer(r) respectively at the trial site. Follow up was done for 30 days. A
      total of 82 participants were included for analysis. RESULTS: A standardized
      aqueous extract of H. sabdariffa L. did not improve iron status in anemic adults
      in malaria endemic region (P>0.005). However, there was evidence to support the
      safety of the extract for human consumptions as herbal supplement. Iron and
      organic acids contents of H. sabdariffa L. extract showed the potential of
      improving hematopoietic parameters. Studies with bigger sample size are therefore
      needed to establish the efficacy of the extract when concurrently used with
      malaria chemoprophylaxis in malaria endemic areas.

PMID- 28755972
TI  - Anoectochilus roxburghii: A review of its phytochemistry, pharmacology, and
      clinical applications.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus roxburghii (Orchidaceae), also
      known as Jinxianlian (Simplified Chinese: ) and Jinxianlan (Simplified Chinese:
      ), is valued in many Asian countries, where this plant species is used for
      medicinal, culinary, and ornamental purposes. As a food, A. roxburghii is widely
      used as a treatment booster and medicine because of its various beneficial
      properties; these include, most notably, the curative effects of heat dissipation
      and cooling of blood, elimination of dampness, detoxification, and immunity
      enhancement. AIM OF THIS REVIEW: This review aims to provide up-to-date
      information on the phytochemistry, pharmacology, and clinical applications of A.
      roxburghii. MATERIALS AND METHODS: Relevant information on A. roxburghii was
      obtained by an online search of worldwide-accepted scientific databases (Web of
      Science, ScienceDirect, Elsevier, Springer, NCBI, ACS Publications, CNKI, and
      Wanfang data). RESULTS: Phytochemical investigations have revealed that the major
      chemical constituents of A. roxburghii are polysaccharides, flavonoids,
      glycosides, organic acids, volatile compounds, steroids, triterpenes, alkaloids,
      and nucleosides. These compounds have been proven to be the main bioactive
      substances responsible for pharmacological activities such as antidiabetic,
      antilipemic, anti-inflammatory, antiviral, liver protective, renal protective,
      immunomodulatory, abirritant, sedative, and antineoplastic effects. CONCLUSIONS:
      A variety of dosage forms of A. roxburghii are currently being applied to
      patients suffering from hyperuricemia, type 2 diabetes mellitus, chronic
      hepatitis B, Helicobacter pylori infection, cough-variant asthma, and other
      conditions. Nevertheless, further research is needed to clarify A. roxburghii
      absorption, distribution, metabolic, and excretion pathways. Moreover, the
      toxicology in A. roxburghii and A. formosanus are also in urgent need of
      research, especially long-term in vivo chronic toxicity tests need to be carried
      out.

PMID- 28755973
TI  - l-Cysteine supplementation increases insulin sensitivity mediated by upregulation
      of GSH and adiponectin in high glucose treated 3T3-L1 adipocytes.
AB  - Diabetic patients have lower blood levels of l-cysteine (LC) and glutathione
      (GSH). This study examined the hypothesis that LC supplementation positively up
      regulates the effects of insulin on GSH and glucose metabolism in 3T3-L1
      adipocyte model. 3T3L1 adipocytes were treated with LC (250 MUM, 2 h) and/or
      insulin (15 or 30 nM, 2 h), and high glucose (HG, 25 mM, 20 h). Results showed
      that HG caused significant increase (95%) in ROS and reduction in the protein
      levels of DsbA-L (43%), adiponectin (64%), GCLC (20%), GCLM (21%), GSH (50%), and
      GLUT-4 (23%) in adipocytes. Furthermore, HG caused a reduction in total (35%) and
      HMW adiponectin (30%) secretion. Treatment with insulin alone significantly (p <
      0.05) reduced ROS levels as well as increased DsbA-L, adiponectin, GCLC, GCLM,
      GSH, and GLUT-4 protein levels, glucose utilization, and improved total and HMW
      adiponectin secretion in HG treated adipocytes compared to HG alone.
      Interestingly, LC supplementation along with insulin caused greater reduction in
      ROS levels and significantly (p < 0.05) boosted the DsbA-L (41% vs LC, 29% vs
      Insulin), adiponectin (92% Vs LC, 84% Vs insulin) protein levels and total (32%
      Vs LC, 22% Vs insulin) and HMW adiponectin (75% Vs LC, 39% Vs insulin) secretion
      compared with the either insulin or LC alone in HG-treated cells. In addition, LC
      supplementation along with insulin increased GCLC (21% Vs LC, 14% insulin), GCLM
      (28% Vs LC, 16% insulin) and GSH (25% Vs LC and insulin) levels compared with the
      either insulin or LC alone in HG-treated cells. Furthermore, LC and insulin
      increases GLUT-4 protein expression (65% Vs LC, 18% Vs Insulin), glucose
      utilization (57% Vs LC, 27% Vs insulin) compared with the either insulin or LC
      alone in HG-treated cells. Similarly, LC supplementation increased insulin action
      significantly in cells maintained in medium contained control glucose. To explore
      the beneficial effect of LC is mediated by the upregulation of GCLC, we knocked
      down GCLC using siRNA in adipoctyes. There was a significant decrease in DsbA-L
      and GLUT-4 mRNA levels and GSH levels in GCLC knockdown adipocytes and LC
      supplementation up regulates GCLC, DsbA-L and GLUT-4 mRNA expression and GSH
      levels in GCLC knockdown cells. These results demonstrated that LC along with
      insulin increases GSH levels thereby improving adiponectin secretion and glucose
      utilization in adipocytes. This suggests that LC supplementation can increase
      insulin sensitivity and can be used as an adjuvant therapy for diabetes.

PMID- 28755974
TI  - A pilot study exploring the effects of ubiquinol on brain genomics after
      traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury is a major cause of morbidity and mortality
      that affects military service members and veterans. PURPOSE: Explore the effects
      of ubiquinol before traumatic brain injury on cerebral gene expression to
      elucidate molecular mechanisms of ubiquinol neuroprotection. METHOD: In this
      experimental study, Fisher rats in the untreated (n = 2) and ubiquinol-treated (n
      = 2) groups received respectively either normal saline or ubiquinol 30 min before
      traumatic brain injury induced by controlled cortical impact. Ribonucleic acid
      sequencing and ingenuity pathway analysis were conducted to detect cerebral gene
      and signaling expression profiles. DISCUSSION: In the ubiquinol-treated group, 67
      ingenuity pathway analysis transcripts in the ubiquinol-treated group were
      statistically different from those in the untreated group (p <.0001).
      CONCLUSIONS: Administering ubiquinol 30 min before traumatic brain injury
      significantly affected cerebral gene expression profiles that may be involved in
      the most fundamental molecular mechanisms of bioenergetics and free radical
      production.

PMID- 28755975
TI  - Microfluidic-Mass Spectrometry Interfaces for Translational Proteomics.
AB  - Interfacing mass spectrometry (MS) with microfluidic chips (MUchip-MS) holds
      considerable potential to transform a clinician's toolbox, providing translatable
      methods for the early detection, diagnosis, monitoring, and treatment of
      noncommunicable diseases by streamlining and integrating laborious sample
      preparation workflows on high-throughput, user-friendly platforms. Overcoming the
      limitations of competitive immunoassays - currently the gold standard in clinical
      proteomics - MUchip-MS can provide unprecedented access to complex proteomic
      assays having high sensitivity and specificity, but without the labor, costs, and
      complexities associated with conventional MS sample processing. This review
      surveys recent MUchip-MS systems for clinical applications and examines their
      emerging role in streamlining the development and translation of MS-based
      proteomic assays by alleviating many of the challenges that currently inhibit
      widespread clinical adoption.

PMID- 28755976
TI  - G-Quadruplexes: Prediction, Characterization, and Biological Application.
AB  - Guanine (G)-rich sequences in nucleic acids can assemble into G-quadruplex
      structures that involve G-quartets linked by loop nucleotides. The structural and
      topological diversity of G-quadruplexes have attracted great attention for
      decades. Recent methodological advances have advanced the identification and
      characterization of G-quadruplexes in vivo as well as in vitro, and at a much
      higher resolution and throughput, which has greatly expanded our current
      understanding of G-quadruplex structure and function. Accumulating knowledge
      about the structural properties of G-quadruplexes has helped to design and
      develop a repertoire of molecular and chemical tools for biological applications.
      This review highlights how these exciting methods and findings have opened new
      doors to investigate the potential functions and applications of G-quadruplexes
      in basic and applied biosciences.

PMID- 28755977
TI  - Plasmas for Treating Cancer: Opportunities for Adaptive and Self-Adaptive
      Approaches.
AB  - Plasma is an ionized gas that is typically formed under high-temperature
      laboratory conditions. Recent progress in atmospheric plasmas has led to cold
      atmospheric plasma (CAP) devices with ion temperatures close to room temperature.
      The unique chemical and physical properties of CAP have led to its use in various
      biomedical applications including cancer therapy. CAP exhibits a spontaneous
      transition from a spatially homogeneous state to a modifiable pattern that is
      subject to self-organization. In this Opinion article, we discuss some new
      applications for plasma in cancer therapy based on plasma self-organization,
      which enables adaptive features in plasma-based therapeutic systems.

PMID- 28755978
TI  - Duration of isoflurane-based surgical anesthesia determines severity of brain
      injury and neurological deficits after a transient focal ischemia in young adult
      rats.
AB  - Tremendous efforts and funds invested in discovery of novel drug treatments for
      ischemic stroke have so far failed to deliver clinically efficacious therapies.
      The reasons for these failures are not fully understood. An indiscriminate use of
      isoflurane-based surgical anesthesia with or without nitrous oxide may act as an
      unconstrained, untraceable source of data variability, potentially causing false
      positive or false-negative results. To test this hypothesis, a common transient
      suture middle cerebral artery occlusion (tMCAO) model of ischemic stroke in young
      adult male rats was used to determine the impact of a typical range of anesthesia
      durations required for this model on data variability (i.e., infarct volume and
      neurological deficits). The animals were maintained on spontaneous ventilation.
      The study results indicated that: (1) Variable duration of isoflurane anesthesia
      prior, during and after tMCAO is a significant source of data variability as
      evidenced by measurements of infarct volume and neurological deficits; and (2)
      Severity of brain injury and neurological deficits after tMCAO is inversely
      related to the duration of isoflurane anesthesia: e.g., in our study, a 90min
      isoflurane anesthesia nearly completely protected brain tissues from tMCAO
      induced injury and thus, would be expected to obscure the effects of stroke
      treatments in pre-clinical trials. To elevate transparency, rigor and
      reproducibility of stroke research and minimize undesirable effects of isoflurane
      on the outcome of novel drug testing, we propose to monitor, minimize and
      standardize isoflurane anesthesia in experimental surgeries and make anesthesia
      duration a required reportable parameter in pre-clinical studies. Specifically,
      we propose to adopt 20-30min as an optimal anesthesia duration that both
      minimizes neuroprotective effects of isoflurane and permits a successful
      completion of surgical procedures in a suture tMCAO model of ischemic stroke in
      rodents. As the mechanisms and neuroprotective, metabolic and immune effects of
      general anesthesia are not fully understood, the results of this study cannot be
      blindly generalized to other anesthetics, animal species and experimental models.

PMID- 28755979
TI  - Genetic variation is associated with RTN4R expression and working memory
      processing in healthy humans.
AB  - The Nogo receptor (NgR) is implicated in neurodevelopmental processes and it
      participates in inhibiting axonal growth. Consistent with its high levels of
      expression in the prefrontal cortex, animal studies indicate that NgR is relevant
      for prefrontal-related cognitive processing. Given that genetic variation may
      alter mechanisms of gene expression impacting molecular and systems-level
      phenotypes, we investigated the association of genetic variation with the
      expression of the NgR coding gene (RTN4R), as well as with prefrontal correlates
      at progressively greater biological distance from gene effects. First, we studied
      the association of single nucleotide polymorphisms (SNPs) with RTN4R mRNA
      expression in postmortem prefrontal cortex of humans without psychiatric
      illnesses. Then, we probed in peripheral blood mononuclear cells (PBMCs) the
      association that we found in prefrontal tissue. Thus, we investigated whether
      functional genetic variation affecting RTN4R expression is also associated with
      prefrontal activity during working memory. We found that rs696884 (A/G) predicted
      these phenotypes. Specifically, the AA genotype was associated with lower RTN4R
      mRNA expression levels in the prefrontal cortex and PBMCs and inefficient
      prefrontal activity during working memory compared to the GG genotype. These
      results suggest that genetic variation associated with RTN4R mRNA expression
      influences prefrontal physiology in healthy individuals. Furthermore, they
      highlight the need for further investigations of the role of NgR in the
      pathophysiology of brain disorders associated with prefrontal dysfunction.

PMID- 28755981
TI  - Assessing Validity of the Fitbit Indicators for U.S. Public Health Surveillance.

PMID- 28755980
TI  - Profiling coping strategies in male and female rats: Potential neurobehavioral
      markers of increased resilience to depressive symptoms.
AB  - Coping strategies have been associated with differential stress responsivity,
      perhaps providing a valuable neurobiological marker for susceptibility to the
      emergence of depressogenic symptoms or vulnerability to other anxiety-related
      disorders. Rats profiled with a flexible coping phenotype, for example, exhibit
      increased neurobiological markers of emotional regulation compared to active and
      passive copers (Bardi et al., 2012; Lambert et al., 2014). In the current study,
      responses of male and female rats to prediction errors in a spatial foraging task
      (dry land maze; DLM) were examined after animals were exposed to chronic
      unpredictable stress (CUS). Brains were processed following the DLM
      training/assessment for fos-activation patterns and several measures of
      neuroplasticity in relevant areas. Behavioral responses observed during both the
      CUS and DLM phases of testing suggested that males and females employ different
      means of gathering information such as increased ambulatory exploration in males
      and rear responses in females. Fecal samples collected during baseline and
      following CUS swim exposure revealed higher corticosterone (CORT) in active
      copers, whereas flexible copers had higher dehydroepiandrosterone (DHEA) and
      DHEA/CORT ratios, both indications of enhanced emotional regulation. Focusing on
      the neural analysis, flexible copers exhibited fewer fos-immunoreactive cells in
      the basolateral amygdala and a trend toward lower activation in the insula while
      encountering the prediction error associated with the DLM probe trial. Coping
      profiles also differentially influenced markers of neuroplasticity; specifically,
      flexible copers exhibited higher levels nestin-immunoreactivity (ir). Further,
      less hippocampal glucocorticoid receptor-ir was observed in the flexible copers
      than the active and passive copers. In sum, flexible coping rats exhibited
      evidence of emotional resilience as indicated by several neurobiological
      measures; however, despite increased rates of depression and related symptoms
      reported in human females, sex effects weren't as pervasive as coping strategy
      profiles in the analysis of neurobiological markers employed in the current
      study.

PMID- 28755982
TI  - Use and Perceptions of Caffeinated Energy Drinks and Energy Shots in Canada.
AB  - INTRODUCTION: In Canada, energy drinks and energy shots are currently classified
      and regulated differently (food and drugs versus natural health products,
      respectively), on the assumption that they are used and perceived differently.
      The current study examined potential differences in use and perceptions of energy
      drinks and shots. METHODS: An online survey was conducted in 2015 using a
      national commercial online panel of youth and young adults aged 12-24 years
      (n=2,040 retained for analysis in 2016). Participants were randomized to view an
      image of an energy shot or drink, and were asked about 14 potential reasons for
      using the product. Past consumption of each product was also assessed. Chi-square
      and t-tests were conducted to examine differences in use and perceptions between
      products. RESULTS: Overall, 15.6% of respondents reported using both energy shots
      and drinks. Of all respondents, <1% had tried only energy shots, whereas 58.0%
      had tried only energy drinks. For each product, the most commonly reported
      reasons for use were "to stay awake" and "to increase concentration or
      alertness." Out of 14 potential reasons for use, respondents were significantly
      more likely to endorse seven of the reasons for energy drinks rather than shots;
      however, the magnitude of these differences was modest and the ordering of the
      reasons for use of each product was comparable. CONCLUSIONS: Despite differences
      in prevalence of ever-use of energy shots and drinks, consumption patterns and
      perceived reasons for using the products are similar. The findings provide little
      support for regulating energy shots differently than energy drinks.

PMID- 28755984
TI  - Penehyclidine hydrochloride preconditioning provides cardiac protection in a rat
      model of myocardial ischemia/reperfusion injury via the mechanism of
      mitochondrial dynamics mechanism.
AB  - To investigate that penehyclidine hydrochloride (PHC) plays a cardiac protection
      role in myocardial ischemia/reperfusion injury (IRI) through mitochondrial
      dynamics mechanism. Rat model of myocardial I/R injury was established by the
      ligation of left anterior descending coronary artery for 30min followed by 3h
      perfusion. Before I/R, the rats were pretreated with or without PHC. Cardiac
      function was measured by echocardiography. The activities/levels of myocardial
      enzymes, oxidants and antioxidant enzymes were detected. Evans blue/TTC double
      staining was performed to assess infarct size. Cell apoptosis was evaluated by
      TUNEL assay. Western blot and real time fluorescent quantitative PCR was
      performed to analyze the expression of Drp1, Mfn1, Mfn2. Meanwhile, the rats were
      given a single injection of PHC before I/R. The effects of PHC on myocardial
      infarct and cardiac function were investigated after 7 days post-reperfusion. Our
      results showed that PHC pretreatment improved imbalance of mitochondrial dynamics
      induced by oxidative stressor in IRI. PHC preconditioning alleviated apoptotic
      rate of cell by improving the imbalance of mitochondrial dynamics in IRI.
      Meanwhile, we showed that PHC remarkably improved cardiac function, myocardial
      injury by decreasing infarct size and attenuated levels of myocardial enzyme.
      Additionally, PHC also exerted long-term cardiac protection in a rat model of I/R
      injury by decreasing infarct size and improving cardiac function. These results
      suggested that PHC could efficiently protect the rats against I/R-induced
      myocardial injury via the mechanism of mitochondrial dynamics.

PMID- 28755985
TI  - Peripheral and central sites of action for anti-allodynic activity induced by the
      bifunctional opioid/NPFF receptors agonist BN-9 in inflammatory pain model.
AB  - The activation of opioid and neuropeptide FF (NPFF) receptors plays important
      roles to modulate nociceptive signal in inflammatory pain states. Recently, BN-9
      (Tyr-D. Ala-Gly-Phe-Gln-Pro-Gln-Arg-Phe-NH2) was pharmacologically characterized
      as a novel bifunctional agonist at both opioid and NPFF receptors. In the present
      study, the anti-allodynic activity and site(s) of action of BN-9 were assessed in
      a mouse model of carrageenan-induced inflammatory pain. In mice, BN-9 induced a
      dose-dependent anti-allodinic effect through opioid receptor at supraspinal or
      spinal level, and this effect was augmented by pretreatment with the NPFF
      receptor antagonist at the same level. In contrast, peripheral administration of
      BN-9 produced opioid receptor-mediated anti-allodynia, which was insensitive of
      the NPFF receptor antagonist. In addition, systemic BN-9 produced anti-allodynic
      effect via opioid receptors, independent of NPFF system. Therefore, these data
      indicate that central, peripheral or systemic administrations of BN-9 exert
      potent analgesic activities in inflammatory pain model via opioid receptor, and
      central effects of BN-9 are associated with NPFF system. Interestingly, systemic
      anti-allodynia of BN-9 was blocked by intraperitoneal administration of the
      opioid receptor antagonists, naloxone and naloxone methiodide, but not by
      intracerebroventricular injection of the peripherally acting opioid antagonist
      naloxone methiodide. Furthermore, BN-9-induced systemic anti-allodynia was
      reversed by intraplantar administration of naloxone, but not by peripheral
      administration of the NPFF receptor antagonist. Taken together, our data further
      suggest that systemic BN-9-induced anti-allodynic effect is mainly mediated by
      peripheral opioid receptors, independent of NPFF receptors.

PMID- 28755987
TI  - Measuring Loneliness: Are There Method Factors?

PMID- 28755986
TI  - Investigating the involvement of glycogen synthase kinase-3beta and gap junction
      signaling in TRPV1 and remote hind preconditioning-induced cardioprotection.
AB  - Remote ischemic preconditioning (RIPC) is the phenomenon that harnesses the
      body's endogenous protective mechanisms against prolonged ischemia-reperfusion
      induced injury. The present study aimed to explore the involvement of glycogen
      synthase kinase-3beta and gap junction signaling in TRPV1 and remote hind
      preconditioning-induced cardioprotection. In the present study, four consecutive
      cycles (5min of ischemia-reperfusion) of remote hind limb preconditioning
      stimulus were delivered using a blood pressure cuff fastened at the inguinal
      level of the rat. The isolated rat hearts were mounted on the Langendorff's
      apparatus and were exposed to 30min of global ischemia-120min of reperfusion.
      Sustained ischemia-reperfusion led to cardiac injury that was assessed in terms
      of infarct size, LDH release, CK release, LVDP, +dp/dtmax, -dp/dtmin, heart rate
      and coronary flow rate. The pharmacological agents employed in the present study
      included capsaicin (10mg/kg) as TRPV1 channel activator, AR-A014418 (1 and
      3mg/kg) as glycogen synthase kinase-3beta inhibitor and carbenoxolone disodium
      (50 and 100mg/kg) as gap junction blocker. Remote hind limb, capsaicin and AR
      A014418 preconditioning led to significant reduction in the infarct size, LDH
      release, CK release and improved LVDP, +dp/dtmax, -dp/dtmin, heart rate and
      coronary flow rate. However, remote hind limb, capsaicin and AR-A014418
      preconditioning-induced cardioprotective effects were remarkably reduced in the
      presence of carbenoxolone (100mg/kg). This indicates that remote preconditioning
      stimulus probably activates TRPV1 channels that may inhibit glycogen synthase
      kinase-3beta activity which subsequently enhances gap junction coupling to
      produce cardioprotective effects.

PMID- 28755988
TI  - Acute Affective Reactivity and Quality of Life in Older Adults with Amnestic Mild
      Cognitive Impairment: A Functional MRI Study.
AB  - OBJECTIVES: Poor quality of life (QoL) is a major concern among older adults with
      amnestic mild cognitive impairment (MCI). Maladaptive affective regulation and
      its relevant frontal dysfunction that are often observed in older adults with MCI
      may provide an insight into the understanding of their QoL. METHODS: In this case
      controlled study, participants (MCI patients, N = 18; healthy comparisons [HC], N
      = 21) completed cognitive tasks, and underwent resting-state functional magnetic
      resonance imaging (rs-fMRI) immediately before and after the tasks. The amplitude
      of low-frequency fluctuations (ALFF) of rs-fMRI signals was calculated to examine
      the brain's spontaneous activity. The change in valence from the Self-Assessment
      Manikin indexed affective reactivity. QoL was assessed using Quality of Life-AD
      measure. Multiple mediator model was used to examine the mediating effect of
      frontal regions' ALFF reactivity between the affective reactivity and QoL.
      RESULTS: The MCI group had significantly worse QoL and more negative affective
      reactivity than HC group. Less negative affective reactivity was significantly
      associated with better QoL in MCI not HC. ALFF in the anterior cingulate cortex,
      medial prefrontal cortex (MPFC), and superior frontal gyrus (SFG) increased
      significantly less after cognitive tasks in MCI than HC. For the entire sample,
      greater increases of ALFF in MPFC and SFG were significantly associated with
      better QoL, and SFG alone significantly mediated the association between
      affective reactivity and QoL. CONCLUSIONS: Enhancing SFG activation, especially
      among those with MCI, may provide a therapeutic target for addressing the
      negative impact of maladaptive affective regulation on QoL.

PMID- 28755989
TI  - Apathy Mediates Cognitive Difficulties in Geriatric Depression.
AB  - OBJECTIVE: Cognitive impairment associated with late-life depression can persist
      after remission of mood symptoms. Apathy, a common symptom of late-life
      depression, often leads to worse clinical outcomes. We examined if severity of
      apathy mediates cognitive difficulties in a cohort of older adults with major
      depression. METHODS: One hundred thirty-eight older adults with depression (54.4%
      female; mean [SD] age: 69.7 [7.4] years; mean [SD] education:15.6 [2.7] years)
      were recruited to participate in a treatment study, and only baseline data were
      analyzed. All participants received a comprehensive evaluation of depression,
      apathy, and cognition. We examined whether apathy mediated the relationship
      between depression and cognition, focusing our attention on memory and cognitive
      control. We then explored whether the mediation effects differed across women and
      men. RESULTS: Increased apathy was significantly associated with worse depression
      and lower performance in the cognitive control domain but not in memory. Higher
      depressive scores were significantly associated with worse cognitive control but
      not memory. Mediation analyses revealed a significant indirect effect on
      cognitive control by depression through increased apathy scores with the mediator
      accounting for 21% of the total effect. Stratifying by sex, we found that women
      exhibited a significant indirect effect, with the mediator accounting for 47% of
      the total effect, whereas there was no mediation by apathy in men. CONCLUSIONS:
      The findings imply that increased apathy mediates the relationship between
      cognition and depression. The identification of mediating effects may inform
      future treatment strategies and preventive interventions that can focus on
      decreasing apathy to improve cognition in late-life depression.

PMID- 28755990
TI  - NF-kappaB mediated miR-130a modulation in lung microvascular cell remodeling:
      Implication in pulmonary hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease
      which is associated with pulmonary arterial endothelial cells (PAEC) dysfunction
      and pulmonary arterial smooth muscle cells proliferation. Moreover, inflammation
      is contributing a critical role in EC dysfunction and remains elusive. Nuclear
      factor-kappa B (NF-kappaB) is a master transcriptional regulator in various
      cardiovascular pathologies; but, NF-kappaB's role in EC dysfunction in unknown.
      Our previous study using cardiac and lung specific IkappaBalpha mutant mice (3M
      and IKBM) showed that PAH induced right ventricular hypertrophy (RVH) was
      prevented in monocrotaline (MCT) treated 3M and IKBM mice, compared to the wild
      type mice. Recently, microRNAs (miRNAs) have emerged as a new class of post
      transcriptional regulators in vascular remodeling; but, NF-kappaB regulated miRNA
      modulation in EC dysfunction is unknown. Using miRNA array analysis, we
      identified miR-130a which is upregulated in MCT-induced PAH mouse model, as a
      possible candidate to study. We showed that overexpressing miR-130a in lung
      microvascular endothelial cells (MVEC) promoted activation of alpha-smooth muscle
      actin, a critical component in endothelial-to-mesenchymal transition in EC
      remodeling. In this study, we demonstrated that bone morphogenetic protein
      receptor 2 (BMPR2) was a target for miR-130a and miR-130a was regulated by NF
      kappaB which controlled apoptosis and vascular genes in MVEC. The findings reveal
      that NF-kappaB-mediated miR-130a modulation is critical in lung vascular
      remodeling.

PMID- 28755991
TI  - Optimization of high-concentration endostatin formulation: Harmonization of
      excipients' contributions on colloidal and conformational stabilities.
AB  - Recently, increasing research efforts have been devoted into developing high
      concentration protein drugs for subcutaneous injection, especially for those with
      short half-lives and high-dose requirement. Proteins at high concentrations
      normally present increased colloidal and structural instability, such as
      aggregation, fibrillation and gelation, which significantly challenges the high
      concentration formulation development of protein drugs. Here we used endostatin,
      a 20kD recombinant protein, as a model drug for high-concentration formulation
      optimization. The colloidal and conformational stability of endostatin at high
      concentration of 30mg/mL were investigated in formulations containing various
      excipients, including saccharides (mannitol, sorbitol and sucrose), salts (ArgHCl
      and NaCl), and surfactants (tween 20 and 80). Protein fibrillation was
      characterized and semi-quantified by optical polarized light microscopy and
      transmission electron microscopy, and the amount of fiber formation at elevated
      temperature of 40 degrees C was determined. The soluble protein aggregates were
      characterized by dynamic and static light scattering before and after dilution.
      The conformational stability were characterized by polyacrylamide gel
      electrophoresis, fluorescence, circular dichroism, and differential scanning
      calorimetry. We observed that the soluble aggregation, fibrillation and gelation,
      induced by conformational and colloidal instabilities of the protein solution,
      could be substantially optimized by using suitable stabilizers such as
      combinations of saccharides and surfactants; while formation of gel and soluble
      aggregates at high protein concentration (e.g., 30mg/mL) and elevated temperature
      (40 degrees C) could be prevented by avoiding the usage of salts. It's worth
      emphasizing that some stabilizers, such as salts and surfactants, could show
      opposite contributions in conformational and colloidal stabilities of endostatin.
      Therefore, cautions are needed when one attempts to correlate the colloidal
      stability of high-concentration proteins with their conformational stability, and
      the colloidal and conformational protein stabilities must be harmonized by a
      balanced selection of various types of excipients.

PMID- 28755992
TI  - Microgels of silylated HPMC as a multimodal system for drug co-encapsulation.
AB  - Combined therapy is a global strategy developed to prevent drug resistance in
      cancer and infectious diseases. In this field, there is a need of multifunctional
      drug delivery systems able to co-encapsulate small drug molecules, peptides,
      proteins, associated to targeting functions, nanoparticles. Silylated hydrogels
      are alkoxysilane hybrid polymers that can be engaged in a sol-gel process,
      providing chemical cross linking in physiological conditions, and functionalized
      biocompatible hybrid materials. In the present work, microgels were prepared with
      silylated (hydroxypropyl)methyl cellulose (Si-HPMC) that was chemically cross
      linked in soft conditions of pH and temperature. They were prepared by an
      emulsion templating process, water in oil (W/O), as microreactors where the
      condensation reaction took place. The ability to functionalize the microgels, so
      called FMGs, in a one-pot process, was evaluated by grafting a silylated
      hydrophilic model drug, fluorescein (Si-Fluor), using the same reaction of
      condensation. Biphasic microgels (BPMGs) were prepared to evaluate their
      potential to encapsulate lipophilic model drug (Nile red). They were composed of
      two separate compartments, one oily phase (sesame oil) trapped in the cross
      linked Si-HPMC hydrophilic phase. The FMGs and BPMGs were characterized by
      different microscopic techniques (optic, epi-fluorescence, Confocal Laser
      Scanning Microscopy and scanning electronic microscopy), the mechanical
      properties were monitored using nano indentation by Atomic Force Microscopy
      (AFM), and different preliminary tests were performed to evaluate their chemical
      and physical stability. Finally, it was demonstrated that it is possible to co
      encapsulate both hydrophilic and hydrophobic drugs, in silylated microgels, that
      were physically and chemically stable. They were obtained by chemical cross
      linking in soft conditions, and without surfactant addition during the
      emulsification process. The amount of drug loaded was in favor of further
      biological activity. Mechanical stimulations should be necessary to trigger drug
      release.

PMID- 28755993
TI  - Breaching barriers in glioblastoma. Part I: Molecular pathways and novel
      treatment approaches.
AB  - Glioblastoma multiforme (GBM) is the most common primary brain tumour, and the
      most aggressive in nature. The prognosis for patients with GBM remains poor, with
      a median survival time of only 1-2 years. The treatment failure relies on the
      development of resistance by tumour cells and the difficulty of ensuring that
      drugs effectively cross the dual blood brain barrier/blood brain tumour barrier.
      The advanced molecular and genetic knowledge has allowed to identify the
      mechanisms responsible for temozolomide resistance, which represents the standard
      of care in GBM, along with surgical resection and radiotherapy. Such resistance
      has motivated the researchers to investigate new avenues for GBM treatment
      intended to improve patient survival. In this review, we provide an overview of
      major obstacles to effective treatment of GBM, encompassing biological barriers,
      cancer stem cells, DNA repair mechanisms, deregulated signalling pathways and
      autophagy. New insights and potential therapy approaches for GBM are also
      discussed, emphasizing localized chemotherapy delivered directly to the brain,
      immunotherapy, gene therapy and nanoparticle-mediated brain drug delivery.

PMID- 28755994
TI  - Non-invasive strategies for targeting the posterior segment of eye.
AB  - The safe and effective treatment of eye diseases has been remained a global myth.
      Several advancements have been done and various drug delivery and treatment
      techniques have been suggested. The Posterior segment disorders are the leading
      cause of visual impairments and blindness. Targeting the therapeutic agents to
      the anterior and posterior segments of the eye has attracted extensive attention
      from the scientific community. Significant key factors in the success of ocular
      therapy are the development of safe, effective, economic and non-invasive novel
      drug delivery systems. These specialized non-invasive ocular drug delivery
      systems revolutionized the drug delivery strategies by overcoming the
      limitations, provided targeted delivery to the ocular tissues by avoiding larger
      doses, and reducing the toxicity encountered by the conventional approaches.
      These non-invasive systems are fabricated by ingredients encompassing
      biodegradability, biocompatibility, mucoadhesion, solubility and permeability
      enhancement and stimuli responsiveness. The variety of routes are utilized to
      provide minimally invasive drug delivery to the patients without any discomfort
      and pain. This review is focused on the brief introduction, types, significance,
      preparation techniques, components and mechanism of drug release of non-invasive
      systems, including in situ gelling systems, microspheres, iontophoresis,
      nanoparticles, nanosuspensions and specialized novel emulsions.

PMID- 28755995
TI  - The Diagnosis and Surgical Approach of Uterine Septa.
AB  - Uterine septa are a class of mullerian duct anomaly that, similar to other
      classes, are associated with poor reproductive outcomes; however, they are unique
      because these poor outcomes, particularly recurrent pregnancy loss, may be
      responsive to surgical correction. The current evidence regarding septoplasty is
      difficult to interpret because the definitions of a uterine septum, methods to
      diagnose it, and hysteroscopic techniques used for treatment are variable and
      generally of poor to moderate quality. Robust data on outcomes, particularly live
      births, after septoplasty are not available at this time. This review aims to
      examine the evidence on this contentious issue. A search of the literature was
      conducted using the MEDLINE, Embase, and Cochrane databases from 2002 to present
      with included articles reporting on clinical and/or imaging diagnosis of a
      uterine septum, operative techniques for uterine septoplasty, or clinical
      outcomes for women with uterine septa. The initial search revealed 4997
      potentially relevant articles with 36 full-text articles included after the
      removal of nonrelevant titles, including 16 diagnostic studies, 17 surgical
      studies, and 3 studies on clinical outcomes. Where access to 3-dimensional
      transvaginal ultrasound or magnetic resonance imaging exists, these imaging
      modalities offer a highly sensitive and specific method of diagnosing a uterine
      septum without invasive diagnosis although this is operator dependent. Despite
      hysteroscopic septoplasty being described for over 40 years, there remains a lack
      of high-quality data to support hysteroscopic septoplasty and which women would
      most benefit from the procedure. There is no evidence for pre- or postoperative
      treatments nor has a single surgical approach been identified as superior than
      another although an important end point of live birth rates is largely unreported
      in these trials. Although several classification systems have been described, the
      diagnostic categorization of septal variants has limited a meaningful approach to
      this issue in both the clinical and research setting.

PMID- 28755996
TI  - Receptor visualization and the atomic bomb. A historical account of the
      development of the chemical neuroanatomy of receptors for neurotransmitters and
      drugs during the Cold War.
AB  - This is a historical account of how receptors for neurotransmitters and drugs got
      to be seen at the regional, cellular, and subcellular levels in brain, in the
      years going from the end of the World War II until the collapse of the Soviet
      Union, the Cold War (1945-1991). The realization in the US of the problem of
      mental health care, as a consequence of the results of medical evaluation for
      military service during the war, let the US Government to act creating among
      other things the National Institute for Mental Health (NIMH). Coincident with
      that, new drug treatments for these disorders were introduced. War science also
      created an important number of tools and instruments, such as the radioisotopes,
      that played a significant role in the development of our story. The scientific
      context was marked by the development of Biochemistry, Molecular Biology and the
      introduction in the early 80's of the DNA recombinant technologies. The concepts
      of chemical neurotransmission in the brain and of receptors for drugs and
      transmitters, although proposed before the war, where not generally accepted.
      Neurotransmitters were identified and the mechanisms of biosynthesis, storage,
      release and termination of action by mechanisms such as reuptake, elucidated.
      Furthermore, the synapse was seen with the electron microscope and more important
      for our account, neurons and their processes visualized in the brain first by
      fluorescence histochemistry, then using radioisotopes and autoradiography, and
      later by immunohistochemistry (IHC), originating the Chemical Neuroanatomy. The
      concept of chemical neurotransmission evolved from the amines, expanded to
      excitatory and inhibitory amino acids, then to neuropeptides and finally to gases
      and other "atypical" neurotransmitters. In addition, coexpression of more than
      one transmitter in a neuron, changed the initial ideas of neurotransmission. The
      concept of receptors for these and other messengers underwent a significant
      evolution from an abstract chemical concept to their physical reality as gene
      products. Important steps were the introduction in the 70's of radioligand
      binding techniques and the cloning of receptor genes in the 80's. Receptors were
      first visualized using radioligands and autoradiography, and analyzed with the
      newly developed computer-assisted image analysis systems. Using Positron Emission
      Tomography transmitters and receptors were visualized in living human brain. The
      cloning of receptor genes allowed the use of in situ hybridization histochemistry
      and immunohistochemistry to visualize with the light and electron microscopes the
      receptor mRNAs and proteins. The results showed the wide heterogeneity of
      receptors and the diversity of mode of signal transmission, synaptic and extra
      synaptic, again radically modifying the early views of neurotransmission. During
      the entire period the interplay between basic science and Psychopharmacology and
      Psychiatry generated different transmitter or receptor-based theories of brain
      drug action. These concepts and technologies also changed the way new drugs were
      discovered and developed. At the end of the period, a number of declines in these
      theories, the use of certain tools and the ability to generate new diagnostics
      and treatments, the end of an era and the beginning of a new one in the research
      of how the brain functions.

PMID- 28755997
TI  - Editorial for the special issue: Monoamine transporters in health and disease.

PMID- 28755998
TI  - Loperamide-Induced Torsades de Pointes: A Case Series.
AB  - BACKGROUND: Loperamide is an over-the-counter, inexpensive, antidiarrheal opioid
      that can produce life-threatening toxicity at high concentrations. CASE REPORT 1:
      A 28-year-old man with a history of depression and substance abuse disorder (SUD)
      presented to the emergency department (ED) with shortness of breath and
      lightheadedness. He ingested large amounts of loperamide daily. The patient's
      initial electrocardiogram (ECG) demonstrated sinus rhythm, right axis deviation,
      undetectable PR interval, QRS 168 ms, and QTc 693 ms. He was administered
      intravenous sodium bicarbonate and magnesium sulfate and admitted to the
      intensive care unit, eventually developing Torsades de Pointes (TdP). He was
      given lidocaine and isoproterenol infusions, and an external pacemaker was
      placed. He was discharged in stable condition on hospital day (HD) 16. CASE
      REPORT 2: A 39-year-old woman with a history of hepatitis C, depression, and SUD
      was transported to the ED after reported seizure-like activity. The patient
      experienced TdP in the ED and admitted to ingesting large amount of loperamide
      daily. An ECG demonstrated sinus rhythm, right axis deviation, PR interval 208
      ms, QRS interval 142 ms, and QTc 687 ms. She was administered intravenous
      magnesium, sodium bicarbonate, and isoproterenol. After intensive care unit
      admission, the patient experienced no further TdP and was discharged on HD 6. WHY
      SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should
      proceed with caution when treating patients with loperamide toxicity. Even in
      asymptomatic patients and drug discontinuance, obtain consultation with a medical
      toxicologist, promptly treat ECG abnormalities aggressively, and admit all
      patients for further monitoring.

PMID- 28755999
TI  - Assessment of the reliability of the accelerometers feedback devices depending on
      the surface on which cardiopulmonary resuscitation is performed.

PMID- 28756000
TI  - A novel mutation of WDR62 gene associated with severe phenotype including
      infantile spasm, microcephaly, and intellectual disability.
AB  - The autosomal recessive form of primary microcephaly (MCPH) is a rare disorder
      characterized by head circumference of at least 3 standard deviation below the
      mean. The MCPH exhibits genetic heterogeneity with thirteen loci (MCPH1-MCPH13)
      identified, and associated with variable degree of intellectual disability. It
      has been reported that WDR62 is the second causative gene of autosomal recessive
      microcephaly (MCPH2) playing a significant role in spindle formation and the
      proliferation of neuronal progenitor cells. We report a clinical feature,
      electroclinical findings, and clinical course of a patient with a severe
      phenotype of MCPH2 including microcephaly, refractory infantile spasms and
      intellectual disability. Genetic analysis detected a new homozygous splicing
      variant c.3335+1G>C in the WD repeat domain 62 (WDR62) gene, inherited from both
      heterozygous healthy parents, and an additional new heterozygous missense
      mutation c.1706T>A of G protein-coupled receptor 56 (GPR56) gene inherited from
      his healthy father. The study seeks to broaden the knowledge of clinical and
      electroclinical findings of MCPH2 and to contribute to a better characterization
      of the genotype-phenotype correlation.

PMID- 28756001
TI  - Oestrogen receptor distribution related to functional thymus anatomy of the
      European sea bass, Dicentrarchus labrax.
AB  - In jawed vertebrates, the crosstalk between immune and endocrine system as well
      as many fundamental mechanisms of T cell development are evolutionary conserved.
      Oestrogens affect mammalian thymic function and plasticity, but the mechanisms of
      action and the oestrogen receptors involved remain unclear. To corroborate the
      oestrogenic regulation of thymic function in teleosts and to identify the
      implicated oestrogen receptor subtypes, we examined the distribution of nuclear
      and membrane oestrogen receptors within the thymus of the European Sea bass,
      Dicentrarchus labrax, in relation to its morpho-functional organisation.
      Immunohistological analysis specified thymus histology and organisation in
      teleosts and described, for the first time, Hassall's corpuscle like structures
      in the medulla of sea bass. All oestrogen receptors were expressed at the
      transcript and protein level, both in T cells and in stromal cells belonging to
      specific functional areas. These observations suggest complex regulatory actions
      of oestrogen on thymic function, notably through the stromal microenvironment,
      comprising both, genomic and non-genomic pathways that are likely to affect T
      cell maturation and trafficking processes. Comparison with birds, rodents and
      humans supports the thymic localization of oestrogen receptors and suggests that
      oestrogens modulate T cell maturation in all gnathostomes.

PMID- 28756002
TI  - [Prognostic factors of advanced stage non-small-cell lung cancer].
AB  - INTRODUCTION: Primary lung cancer is the leading cause of cancer death in men in
      the world. Although the introduction of new drugs, new therapeutic strategies and
      despite therapeutic advances, the prognosis is relatively improved during the
      last years. AIM: To evaluate the prognosis of patients with locally advanced or
      metastatic non-small-cell lung cancer (NSCLC) and to identify prognostic factors
      at these stages. METHODS: A retrospective study, including 140 cases of locally
      advanced or metastatic NSCLC diagnosed in our department between 2003 and 2013.
      RESULTS: The average age was 61+/-10 years (35 to 90 years). Sex ratio was 18.
      The delays management were 80+/-25 days for presentation, 45+/-20 days for the
      diagnostic, while the treatment delay was 8+/-2.33 days. The cancer was at stage
      IIIA in 14%, IIIB in 27% and IV in 59%. Six months and one-year survival was
      between 50 and 74% and between 9 and 25%, respectively. Better survival was
      observed in patients with NSCLC on stage III, having better performance status,
      having comorbid conditions, with prolonged delays management, a short therapeutic
      delay and patients who received specific antitumor treatment. CONCLUSION: The
      prognostic factors in locally advanced and metastatic NSCLC in our patients were:
      stage of cancer, performance status, comorbid conditions, delay of management and
      specific antitumoral treatment. These factors should be considered in the
      management of patients with advanced NSCLC.

PMID- 28756003
TI  - [Complementary and alternative medicine use by lung cancer patients].
AB  - INTRODUCTION: Complementary and alternative medicine (CMA) use is frequent among
      cancer patients. Only few results are available about lung cancer patients. The
      aim of this study was to evaluate how often the CMA were used by lung cancer
      patients and to define the type of CMA used. METHODS: Every lung cancer patients
      with an ongoing chemotherapy in the respiratory department of the University
      Hospital of Nancy were approached between November 2014 to July 2015. A detailed
      and anonymous survey was conducted and the socioeconomic characteristics were
      collected from medical records. RESULTS: Ninety-one patients were questioned. On
      82 patients having answered, 19.5 % had used at least a CMA. The main CMA used
      was the physical exercise in 50 % of the patients. CMA users were significantly
      younger with a mean age of 56.4 years versus 65.4 years (P=0.0007). More than
      half patients did not indicate to their specialist that they used a CMA. The main
      information source was the circle of acquaintances. CONCLUSIONS: CMA use is
      frequent among lung cancer patients. The physical exercise is quoted most of the
      time among the various CMA. There is a real lack of communication on the subject
      between the physician and the patient. It is thus imperative that the
      pulmonologists give much interest to these practices in order to give better
      advices and to reinforce the patient-physician relationship.

PMID- 28756004
TI  - [Pneumomediastinum after cocaine use: A case report].

PMID- 28756005
TI  - [The treatment of pulmonary tuberculosis by artificial pneumothorax].

PMID- 28756006
TI  - Upfront vs. no upfront neck dissection in primary head and neck cancer
      radio(chemo)therapy: Tumor control and late toxicity.
AB  - PURPOSE/OBJECTIVE: The benefit of upfront neck dissection (ND) in locally
      advanced head and neck squamous cell carcinoma (HNSCC) treated with primary
      (chemo-) radiotherapy (R(C)T) is debated. Therefore, we retrospectively compared
      disease control and toxicity between patients who were treated with and without
      upfront ND followed by R(C)T. MATERIAL/METHODS: Two-hundred sixty-four
      consecutive patients with HNSCC without distant metastases at diagnosis and with
      lymph node stage N2-N3 were included in 2 centers. Patients were all treated
      between January 2002 and December 2012, and received definitive R(C)T in center 1
      and upfront ND followed by R(C)T in center 2. Clinical data and outcome were
      assessed retrospectively. Toxicity was scored using the LENT-SOMA scale at 6, 12,
      18 and 24months following the end of treatment. RESULTS: We included 150 patients
      in the group without ND (center 1) and 114 patients in the group with upfront ND
      (center 2). Mean follow up was 5.68years in the group without ND and 5.83years in
      the group with upfront ND. Local, regional and distant control after 2years were
      91.07% and 85.96% (p=0.09), 89.22% and 83.27% (p=0.12) and 76.74% and 75.13%
      (p=0.92) in the group with and without upfront ND, respectively. We did not find
      a significant difference between both groups regarding edema and atrophy at 6,
      12, 18 and 24months. We found a trend at all time-points toward worse outcome in
      the ND group at all time-points (p=0.06). A significantly higher proportion of
      moderate to severe fibrosis (grade >=2) was present in the ND group (p=0.01) at
      all time points. CONCLUSION: There was no significant difference in local,
      regional or distant control and disease-free survival between both patient
      populations. Fibrosis, specifically fibrosis grade >=2 is more prominent
      following upfront ND and R(C)T when compared to R(C)T alone.

PMID- 28756007
TI  - Astroglial Versus Neuronal D-Serine: Check Your Controls!

PMID- 28756008
TI  - Efficacy of the CDK inhibitor dinaciclib in vitro and in vivo in T-cell acute
      lymphoblastic leukemia.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease of the
      blood affecting children, adolescents and adults. Although current treatment
      protocols for T-ALL have improved overall survival, a portion of T-ALL patients
      still experiences treatment failure. Thus, the development of novel therapies is
      needed. In this study, we used several patient-derived T-ALL cell lines to screen
      for an effective drug for T-ALL. Using a panel of 378 inhibitors against
      different kinases, we identified the CDK inhibitor dinaciclib as a potential drug
      for T-ALL. Dinaciclib treatment significantly reduced cell viability and
      completely blocked colony formation. Furthermore, cells treated with dinaciclib
      showed decreased expression of several pro-survival proteins including survivin,
      cyclin T1 and c-MYC. Dinaciclib treatment also increased accumulation of cells in
      G2/M phase and significantly induced apoptosis. Finally, dinaciclib extended
      survival of mice in a T-ALL cell xenograft model. Collectively, these data
      suggest that the CDK inhibitor dinaciclib is an active drug for T-ALL in the
      preclinical settings.

PMID- 28756009
TI  - Flaws in the LNT single-hit model for cancer risk: An historical assessment.
AB  - The LNT single-hit model was derived from the Nobel Prize-winning research of
      Herman J. Muller who showed that x-rays could induce gene mutations in Drosophila
      and that the dose response for these so-called mutational events was linear.
      Lewis J. Stadler, another well-known and respected geneticist at the time,
      strongly disagreed with and challenged Muller's claims. Detailed evaluations by
      Stadler over a prolonged series of investigations revealed that Muller's
      experiments had induced gross heritable chromosomal damage instead of specific
      gene mutations as had been claimed by Muller at his Nobel Lecture. These X-ray
      induced alterations became progressively more frequent and were of larger
      magnitude (more destructive) with increasing doses. Thus, Muller's claim of
      having induced discrete gene mutations represented a substantial speculative
      overreach and was, in fact, without proof. The post hoc arguments of Muller to
      support his gene mutation hypothesis were significantly challenged and weakened
      by a series of new findings in the areas of cytogenetics, reverse mutation,
      adaptive and repair processes, and modern molecular methods for estimating
      induced genetic damage. These findings represented critical and substantial
      limitations to Muller's hypothesis of X-ray-induced gene mutations. Furthermore,
      they challenged the scientific foundations used in support of the LNT single-hit
      model by severing the logical nexus between Muller's data on radiation-induced
      inheritable alterations and the LNT single-hit model. These findings exposed
      fundamental scientific flaws that undermined not only the seminal recommendation
      of the 1956 BEAR I Genetics Panel to adopt the LNT single-hit Model for risk
      assessment but also any rationale for its continued use in the present day.

PMID- 28756010
TI  - Brominated and organophosphorus flame retardants in body wipes and house dust,
      and an estimation of house dust hand-loadings in Dutch toddlers.
AB  - Children generally have higher Flame Retardant (FR) concentrations in serum
      compared to other age groups. Toddler behavior enhances direct contact with house
      dust since their frequent presence proximate to the floor, and their mouthing
      behavior. This study aimed to thoroughly investigate FR levels in body wipes of
      toddlers 8-18 months old) and in indoor dust using a noninvasive sampling
      technique. In this cross-sectional study, body wipes from hands, mouth and back,
      and indoor household dust samples were collected in twenty-one families and
      analyzed for one brominated- and seven organophosphorus FRs (polybrominated
      diphenyl ether 209 (BDE209), tris(2-chloroisopropyl) phosphate (TCIPP),
      tris(chloroethyl) phosphate (TCEP), tris(1,3-dichloroisopropyl) phosphate
      (TDCIPP), tris(phenyl) phosphate (TPHP), tris(methylphenyl) phosphate (TMPP),
      resorcinol bis(diphenyl phosphate) and bisphenol A bis(diphenyl phosphate)).
      Accelerated solvent extraction was used for extraction and the extract was
      measured with liquid chromatography combined with mass spectrometry. Non
      parametric correlation analyses were performed to assess associations. All FRs
      were detected in body- and indoor dust samples (median range: 1.0ng/hand wipe
      (BDE209) to 65ng/hand wipe (TCIPP)) and were mostly correlated with each other.
      We estimated that approximately 260mg dust (range 50-880mg) accumulated on
      toddler's hands per day. Hand-to-mouth frequency was negatively associated with
      FR levels in wipes (tau = -0.38, p = 0.04). With increasing age FR concentrations
      (BDE209, TCEP, TDCIPP, TPHP and TMPP) on hands decreased significantly (p = 0.01
      0.03). Girls had significantly less FRs (TCEP, TCIPP, TPHP and TMPP) on the hands
      (p = 0.01-0.03) than boys. This is to the best of the authors' knowledge the
      first study in Europe that measured brominated- as well as organophosphorus FRs
      in several types of body wipes from toddlers and that estimated the amount of
      house dust that accumulates on toddler's hands.

PMID- 28756011
TI  - Impact of posttraumatic stress symptom dimensions on amygdala reactivity to
      emotional faces.
AB  - Posttraumatic stress disorder (PTSD) is highly prevalent and associated with
      impairment, even at the subthreshold level. It is therefore important to identify
      biological processes that contribute to the pathophysiology of posttraumatic
      stress symptoms (PTSS). Although neuroimaging research has highlighted the
      importance of heightened amygdala reactivity to aversive stimuli in PTSS, not all
      studies have yielded evidence of this relationship. Given that PTSS is comprised
      of four, factor analytically distinct dimensions of symptoms - re-experiencing,
      avoidance, hyperarousal, and negative cognitions and mood - it is possible that
      heightened amygdala reactivity to aversive stimuli is specific to certain PTSS
      clusters. In a sample of 45 trauma-exposed individuals, the present study
      therefore examined how specific PTSS clusters relate to amygdala responding
      during functional magnetic resonance imaging (fMRI) to both negative and positive
      emotional faces during a well-validated social-emotional task, the Emotional Face
      Assessment Task (EFAT). Results indicated that hyperarousal symptoms were
      positively associated with left amygdala reactivity across all emotional face
      conditions. There was no interaction of hyperarousal by condition (i.e., fearful,
      sad, angry, or happy faces), and other PTSS clusters were not associated with
      amygdala reactivity. These results indicate that the hyperarousal cluster of PTSS
      may have a unique relationship with amygdala reactivity to socioemotional
      information. The results also corroborate a growing literature suggesting that
      trauma-exposed individuals characterized by high PTSS hyperarousal symptoms may
      display exaggerated psychophysiological reactivity to appetitive and aversive
      stimuli.

PMID- 28756012
TI  - Design, synthesis, and pharmacological evaluation of a novel series of hormone
      sensitive lipase inhibitor.
AB  - HSL inhibition is a promising approach to the treatment of dyslipidemia. As a
      result of re-optimization of lead compound 2, we identified novel compound 25a
      exhibiting potent inhibitory activity against HSL enzyme and cell with high
      selectivity for cholinesterases (AChE and BuChE). Reflecting its potent in vitro
      activity, compound 25a exhibited antilipolytic effect in rats at 1mg/kg p.o.,
      which indicated that this novel compound is the most potent orally active HSL
      inhibitor. Moreover, compound 25a did not show bioactivation liability.

PMID- 28756013
TI  - 5- or/and 20-O-alkyl-2,3-dehydrosilybins: Synthesis and biological profiles on
      prostate cancer cell models.
AB  - To investigate the effects of alkylation at 5-OH and 20-OH of 2,3-dehydrosilybin
      on prostate cancer cell proliferation, the synthetic approaches to 5- or/and 20-O
      alkyl-2,3-dehydrosilybins, through a multi-step sequence from commercially
      available silybin, have been successfully developed. The first three reactions in
      the syntheses were completed through a one-pot procedure by managing anaerobic
      and aerobic conditions. With these synthetic methods in hand, twenty-one 2,3
      dehydrosilybins, including seven 20-O-alkyl, seven 5,20-O-dialkyl, and seven 5-O
      alkyl-2,3-dehydrosilybins, have been achieved for the evaluation of their
      biological profiles. Our WST-1 cell proliferation assay data indicate that
      nineteen out of the twenty-one 2,3-dehydrosilybins possess significantly improved
      antiproliferative potency as compared with silybin toward both androgen-sensitive
      (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145). 5-O
      Alkyl-2,3-dehydrosilybins were identified as the optimal subgroup that can
      consistently inhibit cell proliferation in three prostate cancer cell models with
      all IC50 values lower than 8uM. Our flow cytometry-based assays also demonstrate
      that 5-O-heptyl-2,3-dehydrosilybin effectively arrests the cell cycle in the
      G0/G1 phase and activates PC-3 cell apoptosis.

PMID- 28756014
TI  - Caffeine and cardiovascular health.
AB  - This report evaluates the scientific literature on caffeine with respect to
      potential cardiovascular outcomes, specifically relative risks of total
      cardiovascular disease (CVD), coronary heart disease (CHD) and acute myocardial
      infarction (AMI), effects on arrhythmia, heart failure, sudden cardiac arrest,
      stroke, blood pressure, hypertension, and other biomarkers of effect, including
      heart rate, cerebral blood flow, cardiac output, plasma homocysteine levels,
      serum cholesterol levels, electrocardiogram (EKG) parameters, heart rate
      variability, endothelial/platelet function and plasma/urine catecholamine levels.
      Caffeine intake has been associated with a range of reversible and transient
      physiological effects broadly and cardiovascular effects specifically. This
      report attempts to understand where the delineations exist in caffeine intake and
      corresponding cardiovascular effects among various subpopulations. The available
      literature suggests that cardiovascular effects experienced by caffeine consumers
      at levels up to 600 mg/day are in most cases mild, transient, and reversible,
      with no lasting adverse effect. The point at which caffeine intake may cause harm
      to the cardiovascular system is not readily identifiable in part because data on
      the effects of daily intakes greater than 600 mg is limited. However, the
      evidence considered within this review suggests that typical moderate caffeine
      intake is not associated with increased risks of total cardiovascular disease;
      arrhythmia; heart failure; blood pressure changes among regular coffee drinkers;
      or hypertension in baseline populations.

PMID- 28756016
TI  - Pharmacological stroke prevention in the elderly with atrial fibrillation in
      Poland - Results of PolSenior study.
AB  - INTRODUCTION: Atrial fibrillation (AF) is the most frequent clinically
      significant arrhythmia, especially common in the elderly. As it is known, AF is
      associated with increased risk of stroke. Little is known about pharmacological
      cardiovascular prevention in the elderly with AF in Poland. OBJECTIVES: The
      purpose of the study was to evaluate the frequency of pharmacological stroke
      prevention among the elderly with AF in Poland and its association with clinical
      characteristics and concomitant cardiovascular risk factors. PATIENTS AND
      METHODS: The analysis included elderly (>=65 years) participants of the PolSenior
      study performed in years 2008-2012. RESULTS: The study group consisted of 4979
      people (mean age: 79.3+/-8.7 years). Among them, there were 875 patients (18.7%)
      with documented history of AF. Pharmacological prevention with the use of vitamin
      K antagonists (VKA) was applied by 117 (13.4%) of the elderly with AF, including
      15 (1.7%) on dual therapy. Additionally, 386 (45.3%) subjects with AF were using
      oral antiplatelet therapy (OAPs), mostly aspirin. Acenocoumarol was much more
      often used than warfarin. New oral anticoagulant drugs (NOACs) were not used at
      all. Only personal income was associated with the use of VKA. No significant
      correlation was found for the age, sex, place of residence and level of
      education. CONCLUSIONS: The study was unique to determine the frequency of
      pharmacological stroke prevention among elderly people with AF in Poland. It
      occurred that oral anticoagulant drugs were applied too rarely in this group of
      patients. Educational programs should be developed among general practitioners
      concerning current recommendations for patients with AF.

PMID- 28756017
TI  - Complications following completion lymphadenectomy versus therapeutic
      lymphadenectomy for melanoma - A systematic review of the literature.
AB  - PURPOSE: Completion lymph node dissection (CLND) following a positive sentinel
      lymph node biopsy (SLNB) has been reported to be less morbid than lymphadenectomy
      for palpable disease (therapeutic lymph node dissection; TLND). The reporting of
      morbidity data can be heterogeneous, and hence no 'average' surgical complication
      rates of these procedures has been reported. This review aims to determine
      complications rates to inform patients undergoing surgery for metastatic
      melanoma. METHODS: A systematic review of English-language literature from 2000
      to 2017, reporting morbidity information about CLND and TLND for melanoma, was
      performed. The methodological quality of the included studies was performed using
      the methodological index for non-randomised studies (MINORS) instrument and
      Detsky score. Pooled proportions of post-operative complications were constructed
      using a random effects statistical model. RESULTS: After application of inclusion
      and exclusion criteria, 18 articles progressed to the final analysis. In relation
      to TLND (1627 patients), the overall incidence of surgical complications was
      39.3% (95% CI 32.6-46.2); including wound infection/breakdown 25.4% (95% CI: 20.9
      30.3); lymphoedema 20.9% (95% CI: 13.8-29.1); and seroma 20.4% (95% CI: 15.9
      25.2). For CLND (1929 patients), the overall incidence of surgical complications
      was 37.2% (95% CI 27.6-47.4); including wound infection/breakdown 21.6% (95% CI:
      13.8-30.6); lymphoedema 18% (95% CI: 12.5-24.2); and seroma 17.9% (95% CI: 10.3
      27). The complication rate was marginally lower for CLND but not to statistical
      significance. DISCUSSION: This study provides information about the incidence of
      complications after CLND and TLND. It can be used to counsel patients about the
      procedures and it sets a benchmark against which surgeons can audit their
      practice.

PMID- 28756018
TI  - Epithelioid sarcomas: How important is loco-regional control?
AB  - AIMS: To investigate the impact of the method of treatment on the oncological
      outcomes in patients with epithelioid sarcomas managed at two international
      speciality sarcoma centres. METHODS: The databases of two centres were used to
      identify patients treated for epithelioid sarcomas between 1985 and 2012.
      Patient, tumor, treatment and outcome data was collected. RESULTS: There were 36
      males and 18 females with a mean age of 38.3 years (range 9-79). Of 49 patients
      who were treated surgically, limb salvage surgery was carried out in 38 patients
      (78%) and limb amputation in 11 (22%). Of 49 total patients who underwent surgery
      for ES, 48 (98%) with ES had negative margin resection and 24 (49%) received
      (neo) adjuvant radiotherapy. Regional lymph node metastases developed in 5 (13%)
      patients. The five-year risk of local recurrence was 14%. The overall survival
      rate at five and ten years was 70% and 66% respectively. In multivariate analysis
      of patients with localized disease and negative margins, survival and risk of
      metastases was worse in those treated by amputation. CONCLUSION: This series has
      shown that although the rate of local recurrence is not influenced by the type of
      surgery, the risk of metastases is higher following amputation. This finding is
      likely due to patients with larger, deeper and more locally advanced tumors
      requiring amputation. However, we could not prove that immediate amputation was
      likely to affect overall survival.

PMID- 28756015
TI  - Mechanical thrombectomy in acute stroke - Five years of experience in Poland.
AB  - OBJECTIVES: Mechanical thrombectomy (MT) is not reimbursed by the Polish public
      health system. We present a description of 5 years of experience with MT in acute
      stroke in Comprehensive Stroke Centers (CSCs) in Poland. METHODS AND RESULTS: We
      retrospectively analyzed the results of a structured questionnaire from 23 out of
      25 identified CSCs and 22 data sets that include 61 clinical, radiological and
      outcome measures. RESULTS: Most of the CSCs (74%) were founded at University
      Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working
      teams are composed of neurologists and neuro-radiologists. All CSCs perform CT
      and angio-CT before MT. In total 586 patients were subjected to MT and data from
      531 of them were analyzed. Mean time laps from stroke onset to groin puncture was
      250+/-99min. 90.3% of the studied patients had MT within 6h from stroke onset;
      59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during
      MT and 4.7% - emergent stenting of a large vessel. M1 of MCA was occluded in
      47.8% of cases. The Solitaire device was used in 53% of cases. Successful
      recanalization (TICI2b-TICI3) was achieved in 64.6% of cases and 53.4% of
      patients did not experience hemorrhagic transformation. Clinical improvement on
      discharge was noticed in 53.7% of cases, futile recanalization - in 30.7%, mRS of
      0-2 - in 31.4% and mRS of 6 in 22% of cases. CONCLUSION: Our results can help
      harmonize standards for MT in Poland according to international guidelines.

PMID- 28756019
TI  - Survival outcome of weak estrogen/progesterone receptor expression in HER2
      negative breast cancer is similar to triple negative breast cancer.
AB  - BACKGROUND: Recent publications have suggested that human epidermal growth factor
      receptor 2 (HER2)-negative breast cancers with "weak" estrogen receptor
      (ER)/progesterone receptor (PR) expression levels by immunohistochemical (IHC)
      analysis were considered as the triple-negative (TN) subtype. This study aimed to
      evaluate the overall survival (OS), disease-free survival rates (DFS), and
      disease-specific survival (DSS) based on ER and PR expression levels into one of
      three groups, ER and PR <1%, ER and PR 1%-20%, and ER or PR >20% by hormone
      therapy. METHODS: Medical records of 3353 breast cancer patients treated from
      2006 to 2013 were retrospectively reviewed. Tumor characteristics, type of
      treatment, OS, DFS and DSS were evaluated among the three patient groups.
      RESULTS: Regarding OS, there were significant differences according to the
      received hormone therapy in the different groups: ER and PR <1% (P = 0.972), ER
      and PR 1%-20% (P = 0.264), and ER or PR >20% (P = 0.014). Regarding DFS and DSS,
      there were also significant differences in the different groups: ER and PR <1% (P
      = 0.611, 0.766), ER and PR 1%-20% (P = 0.847, 0.629), and ER or PR >20% (P =
      0.031, 0.002). CONCLUSIONS: In HER2 negative breast cancer patient with hormone
      therapy, ER and PR expression level of 1%-20% has similar survival outcome to the
      ER and PR expression level of <1% by IHC analysis.

PMID- 28756020
TI  - Identification and characterization of the tyrosinase gene (TYR) and its
      transcript variants (TYR_1 and TYR_2) in the crab-eating macaque (Macaca
      fascicularis).
AB  - Tyrosinase is a copper-containing enzyme that regulates melanin biosynthesis and
      is encoded by the tyrosinase (TYR) gene. Previous studies demonstrated that
      mutations in TYR could lead to oculocutaneous albinism type 1 (OCA1) owing to the
      failure of melanin formation. Although a previous study found that albinism in
      the rhesus monkey was derived from a mutation in TYR, the identification and
      characterization of this gene in non-human primates has not been achieved thus
      far. Thus, using the rapid amplification of cDNA ends (RACE) and internal reverse
      transcription PCR (RT-PCR) we identified the full-length sequence of TYR in the
      crab-eating macaque, and two different transcript variants (TYR_1 and TYR_2).
      While TYR_1 comprised five exons and its coding sequence was highly similar to
      that of humans, TYR_2 comprised four exons and was generated by a third-exon
      skipping event. Interestingly, these two transcripts were also present in the
      African green monkey (Old World monkey) and the common marmoset (New World
      monkey). Deduced amino acid sequence analyses revealed that TYR_2 had a shorter C
      terminal region than TYR_1 owing to the exon-skipping event. Thus, the present
      study is the first to identify and characterize a full-length TYR gene in a non
      human primate, while the further validation of the third-exon-skipping in TYR
      indicates that this event is well conserved in the primate lineage. Therefore,
      this study provides useful and important information for the study of albinism
      using non-human primate models.

PMID- 28756021
TI  - Association of clinical severity of cystic fibrosis with variants in the SLC gene
      family (SLC6A14, SLC26A9, SLC11A1 and SLC9A3).
AB  - INTRODUCTION: Cystic fibrosis (CF) manifests with clinical and histopathological
      variability depending on environmental and genetic factors. Moreover, the genes
      encoding ion channels[rs3788766(SLC6A14), rs7512462(SLC26A9), rs17235416(SLC11A1)
      and rs17563161(SLC9A3)] have been insufficiently studied as modifier genes. Then,
      our objective was associate the variants in the genes of SLC family with 43 CF
      severity markers. METHODS: The variants were identified by real-time-PCR in 188
      CF patients considering the CFTR genotype. Statistical analyses were performed by
      parametric and nonparametric tests. The correction by multiple testing was
      performed by the False Rate Discovery test, alpha=0.05. RESULTS: Depending on the
      CFTR mutations, we found association of: (i) rs3788766*CC with mucoid Pseudomonas
      aeruginosa (OR=0.171; 95%CI=0.029-0.696), non-mucoid P. aeruginosa (OR=0.283;
      95%CI=0.094-0.853) and Staphyloccocus aureus (OR=4.443; 95%CI=1.019-40.64),
      largest FEFmax(p=0.041) and best response to bronchodilator for FEF50%(p=0.033)
      and FEV1/FVC(p=0.044); (ii) rs3788766*CT with early start of pulmonary symptom
      (OR=3.524; 95%CI=1.229-10.1) and osteoporosis (OR=0.203; 95%CI=0.022-0.883);
      (iii) rs3788766*TT with lowest body mass index (OR=4.242; 95%CI=1.505-11.95),
      presence of mucoid P. aeruginosa (OR=3.176; 95%CI=1.29-7.819) and S. aureus
      (OR=0.116; 95%CI=0.004-0.881), highest Bhalla score (p=0.047) and lowest
      FEFmax(p=0.028) and FEF25%(p=0.031) values; (iv) rs7512462*CC with highest
      Shwachman-Kulczycki score (p=0.019), FVC(p=0.043), FEV1(p=0.047),
      FEV1/FVC(p=0.022), FEF50%(p=0.038) and FEF25-75%(p=0.016); (v) rs7512462*CT with
      lowest values of FVC(p=0.034), FEV1(p=0.047), FEV1/FVC(p=0.022), FEF25%(p=0.012),
      FEF50%(p=0.038), FEF75%(p=0.008), FEF25-75%(p=0.016) and ERV(p=0.023); (vi)
      rs7512462*TT with best response to the inhaled bronchodilator for FEV1(p=0.011),
      FEF50%(p=0.019), FEF75%(p=0.036) and FEF25-75%(p=0.008); (vii) rs17234516*Normal
      allele with lowest value of SaO2 (p=0.010) and S. aureus (OR=3.333; 95%CI=1.085
      10.24); (viii) rs17563161*GG with lowest age for onset of digestive symptoms
      (OR=2.564; 95%CI=1.234-5.33). CONCLUSIONS: The clinical and laboratory
      variability of CF were associated with the variants in the genes of SLC family in
      our sample.

PMID- 28756022
TI  - Histone methylase MLL1 coordinates with HIF and regulate lncRNA HOTAIR expression
      under hypoxia.
AB  - Hypoxia signaling plays a critical role in tumor growth, angiogenesis, metastasis
      cancer, and aging. Under hypoxia, hypoxia-inducible factors (HIFs) are stabilized
      and they coordinate the process of hypoxia-induced gene expression and cell
      signaling leading to increased tumor growth. Recent studies indicate that non
      coding RNAs which are closely associated with cancer are abnormally expressed
      under hypoxia. Here, we have investigated the transcriptional regulation of a
      cancer associated long non-coding RNA (lncRNA), HOTAIR, under hypoxic conditions.
      Our studies demonstrate that HOTAIR expression is upregulated under hypoxia in
      colon cancer and several other types of cancer cells. HOTAIR transcription is
      regulated by HIF1alpha which binds to the hypoxia response elements (HRE) present
      in the HOTAIR promoter under hypoxia. HIF1alpha knockdown results in decreased
      HOTAIR expression under hypoxia. Along with HIF1alpha, histone methylases MLL1
      and histone acetylase p300 are enriched at the HOTAIR promoter under hypoxia. The
      levels of H3K4-trimethylation and histone acetylation are also enriched at the
      HOTAIR promoter. Furthermore, knockdown of MLL1 downregulated the hypoxia-induced
      HOTAIR expression, indicating key roles of MLL1 in hypoxia-induced HOTAIR
      expression. Overall, our studies demonstrate that histone methyl-transferase MLL1
      coordinates with HIF1alpha and histone acetyltransferase p300 and regulate
      hypoxia-induced HOTAIR expression. The hypoxia-induced upregulation of HOTAIR
      expression may contribute to its roles in tumorigenesis.

PMID- 28756023
TI  - Febrile rhabdomyolysis of unknown origin in refugees coming from West Africa
      through the Mediterranean.
AB  - OBJECTIVES: Cases of undiagnosed severe febrile rhabdomyolysis in refugees coming
      from West Africa, mainly from Nigeria, has been observed since May 2014. The aim
      of this study was to describe this phenomenon. METHODS: This was a multicentre
      retrospective observational study of cases of febrile rhabdomyolysis reported
      from May 2014 to December 2016 in 12 Italian centres. RESULTS: A total of 48
      cases were observed, mainly in young males. The mean time interval between the
      day of departure from Libya and symptom onset was 26.2 days. An average 8.3
      further days elapsed before medical care was sought. All patients were
      hospitalized with fever and very intense muscle aches. Creatine phosphokinase,
      aspartate aminotransferase, and lactate dehydrogenase values were abnormal in all
      cases. The rhabdomyolysis was ascribed to an infective agent in 16 (33.3%) cases.
      In the remaining cases, the aetiology was undefined. Four out of seven patients
      tested had sickle cell trait. No alcohol abuse or drug intake was reported, apart
      from a single reported case of khat ingestion. CONCLUSIONS: The long incubation
      period does not support a mechanical cause of rhabdomyolysis. Furthermore, viral
      infections such as those caused by coxsackievirus are rarely associated with such
      a severe clinical presentation. It is hypothesized that other predisposing
      conditions like genetic factors, unknown infections, or unreported non
      conventional remedies may be involved. Targeted surveillance of rhabdomyolysis
      cases is warranted.

PMID- 28756024
TI  - Design, synthesis and anticancer activity of N-(1-(4-(dibenzo[b,f][1,4]thiazepin
      11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives.
AB  - Novel N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3
      phenylpropan-2-yl derivatives were designed, synthesized and their chemical
      structures were confirmed by 1H NMR, 13C NMR and Mass spectra. The anticancer
      activities of the newly synthesized compounds were evaluated in vitro against
      three human cancer cell lines including K562, Colo-205 and MDA-MB 231 by MTT
      assay. The screening results showed that five compounds (16b, 16d, 16i, 16p and
      16q) exhibited potent cytotoxic activities with IC50 values between 20 and 40MUM.
      Further in vitro studies revealed that inhibition of sirtuins could be the
      possible mechanism of action of these molecules.

PMID- 28756025
TI  - Direct observation of positive supercoils introduced by reverse gyrase through
      atomic force microscopy.
AB  - Reverse gyrase is a hyperthermophilic enzyme that can introduce positive
      supercoiling in substrate DNA. It is showed in our studies that positive DNA
      supercoils were induced in both pBR322 vector and an artificially synthesized
      mini-plasmid DNA by reverse gyrase. The left-handed structures adopted by
      positively supercoiled DNA molecules could be identified from their right-handed
      topoisomers through atomic force microscopic examination. Additional structural
      comparisons revealed that positively supercoiled DNA molecule AFM images
      exhibited increased contour lengths. Moreover, enzymatic assays showed that the
      positively supercoiled DNA could not be cleaved by T7 endonuclease. Together,
      this suggests that the overwound structure of positive supercoils could prevent
      genomic duplex DNA from randomly forming single-stranded DNA regions and intra
      stranded secondary structures.

PMID- 28756026
TI  - Resistance and clonality in Escherichia coli and Klebsiella spp. and relationship
      with antibiotic consumption in major Lebanese hospitals.
AB  - OBJECTIVES: Extended-spectrum beta-lactamases (ESBLs) are increasingly detected
      globally among Escherichia coli and Klebsiella spp. Studies show a link between
      inappropriate use of antibiotics and resistance. In this study, the profiles of
      ESBLs in E. coli and Klebsiella spp. isolated from three Lebanese hospitals and
      their relationship to antibiotic consumption were determined. METHODS: A total of
      300 E. coli and 91 Klebsiella spp. isolates resistant to third- or fourth
      generation cephalosporins were collected between May 2011 and December 2012.
      Antibiotic susceptibility and consumption data were also collected from 2010
      2012. Double-disk synergy and Etest ESBL assays were performed, followed by PCR
      for ESBL genes. Pulsed-field gel electrophoresis (PFGE) was performed for
      representative isolates. Statistical analysis for consumption and susceptibility
      data over 3 years was performed. RESULTS: Similar to other Lebanese studies, CTX
      M-15 was predominant. Among the Klebsiella spp. isolated in hospitals 1 and 2,
      43% harboured four different ESBLs. Eight Klebsiella spp. and fourteen E. coli
      pulsotypes were detected, showing genetic diversity among isolates. A significant
      correlation was detected between total use of antimicrobial agents and resistance
      to various antibiotics. A correlation was also detected between use of
      penicillins and resistance to aztreonam, ceftazidime and ciprofloxacin, and use
      of third- and fourth-generation cephalosporins and resistance to ceftazidime,
      cefuroxime, cefoxitin and ciprofloxacin in Klebsiella spp. (P<0.05). CONCLUSIONS:
      This study shows the predominance of CTX-M-15 among cephalosporin-resistant E.
      coli and Klebsiella spp. in Lebanese hospitals. It also shows that the heightened
      use of antibiotics could be a driving factor for resistance emergence.

PMID- 28756027
TI  - Key considerations in designing a speech brain-computer interface.
AB  - Restoring communication in case of aphasia is a key challenge for
      neurotechnologies. To this end, brain-computer strategies can be envisioned to
      allow artificial speech synthesis from the continuous decoding of neural signals
      underlying speech imagination. Such speech brain-computer interfaces do not exist
      yet and their design should consider three key choices that need to be made: the
      choice of appropriate brain regions to record neural activity from, the choice of
      an appropriate recording technique, and the choice of a neural decoding scheme in
      association with an appropriate speech synthesis method. These key considerations
      are discussed here in light of (1) the current understanding of the functional
      neuroanatomy of cortical areas underlying overt and covert speech production, (2)
      the available literature making use of a variety of brain recording techniques to
      better characterize and address the challenge of decoding cortical speech
      signals, and (3) the different speech synthesis approaches that can be considered
      depending on the level of speech representation (phonetic, acoustic or
      articulatory) envisioned to be decoded at the core of a speech BCI paradigm.

PMID- 28756028
TI  - Human Papillomavirus Vaccination Uptake before and after the Affordable Care Act:
      Variation According to Insurance Status, Race, and Education (NHANES 2006-2014).
AB  - STUDY OBJECTIVE: The purpose of the study was to compare human papillomavirus
      (HPV) vaccination rates before and after Affordable Care Act (ACA) implementation
      among women, and examine differences according to insurance status and other
      sociodemographic variables. DESIGN, SETTING, AND PARTICIPANTS: This was a cross
      sectional analysis of the National Health and Nutrition Examination Survey
      questionnaire data. Participants (n = 4599) were from a random sample of the
      United States population. INTERVENTIONS AND MAIN OUTCOME MEASURES: HPV
      vaccination status and number of doses received according to age, income,
      education, race, and insurance coverage. RESULTS: Over time, the proportion of
      women reporting HPV vaccination increased from 16.4% to 27.6%, and reporting
      vaccination completion (3 doses) increased from 56.8% to 67.2%. After ACA
      implementation, respondents were 3.3 times more likely to be vaccinated compared
      with before ACA implementation (95% confidence interval [CI], 2.0-5.5) adjusting
      for age, race, and insurance coverage. Similarly, respondents were more likely to
      have received 2 (odds ratio, 2.8; 95% CI, 1.5-5.3) or 3 doses (odds ratio, 5.8;
      95% CI, 2.5-13.6). CONCLUSION: Vaccination uptake increased in a comparison of
      waves of data from before and after ACA implementation. This increase in
      vaccination coverage could be related to the increased preventative service
      coverage, which includes vaccines, required by the ACA. Future studies might
      focus on the role insurance has on vaccination uptake, and meeting Healthy People
      2020 objectives for vaccination coverage.

PMID- 28756030
TI  - Intensive referral to mutual-help groups: A field trial of adaptations for rural
      veterans.
AB  - OBJECTIVE: A multisite field trial testing whether improved outcomes associated
      with intensive referral to mutual help groups (MHGs) could be maintained after
      the intervention was adapted for the circumstances and needs of rural veterans in
      treatment for substance use disorder (SUD). METHODS: In three Veterans Affairs
      treatment programs in the Midwest, patients (N=195) received standard referral
      (SR) or rural-adapted intensive referral (RAIR) and were measured at baseline and
      6-month follow-up. RESULTS: Both groups reported significant improvement at 6
      months, but no significant differences between SR and RAIR groups in MHG
      participation, substance use, addiction severity, and posttraumatic stress
      symptoms. Inconsistent delivery of the intervention resulted in only one-third of
      the RAIR group receiving the full three sessions, but this group reported
      significantly greater 6-month abstinence from alcohol than those receiving no
      sessions. CONCLUSION: Further research should explore implementation problems and
      determine whether consistent delivery of the intervention enhances 12-step
      facilitation. PRACTICE IMPLICATIONS: The addition of rural-specific elements to
      the original intensive referral intervention has not been shown to increase its
      effectiveness among rural veterans.

PMID- 28756031
TI  - Post-learning arousal enhances veridical memory and reduces false memory in the
      Deese-Roediger-McDermott paradigm.
AB  - The Deese-Roediger-McDermott (DRM) paradigm examines false memory by introducing
      words associated with a non-presented 'critical lure' as memoranda, which
      typically causes the lures to be remembered as frequently as studied words. Our
      prior work has shown enhanced veridical memory and reduced misinformation effects
      when arousal is induced after learning (i.e., during memory consolidation). These
      effects have not been examined in the DRM task, or with signal detection
      analysis, which can elucidate the mechanisms underlying memory alterations. Thus,
      130 subjects studied and then immediately recalled six DRM lists, one after
      another, and then watched a 3-min arousing (n=61) or neutral (n=69) video.
      Recognition tested 70min later showed that arousal induced after learning led to
      better delayed discrimination of studied words from (a) critical lures, and (b)
      other non-presented 'weak associates.' Furthermore, arousal reduced liberal
      response bias (i.e., the tendency toward accepting dubious information) for
      studied words relative to all foils, including critical lures and 'weak
      associates.' Thus, arousal induced after learning effectively increased the
      distinction between signal and noise by enhancing access to verbatim information
      and reducing endorsement of dubious information. These findings provide important
      insights into the cognitive mechanisms by which arousal modulates early memory
      consolidation processes.

PMID- 28756029
TI  - Tripartite symbiosis of Sophora tomentosa, rhizobia and arbuscular mycorhizal
      fungi.
AB  - Sophora tomentosa is a pantropical legume species with potential for recovery of
      areas degraded by salinization, and for stabilization of sand dunes. However, few
      studies on this species have been carried out, and none regarding its symbiotic
      relationship with beneficial soil microorganisms. Therefore, this study aimed to
      evaluate the diversity of nitrogen-fixing bacteria isolated from nodules of
      Sophora tomentosa, and to analyze the occurrence of colonization of arbuscular
      mycorrhizal fungi on the roots of this legume in seafront soil. Thus, seeds, root
      nodules, and soil from the rhizosphere of Sophora tomentosa were collected. From
      the soil samples, trap cultures with this species were established to extract
      spores and to evaluate arbuscular mycorhizal fungi colonization in legume roots,
      as well as to capture rhizobia. Rhizobia strains were isolated from nodules
      collected in the field or from the trap cultures. Representative isolates of the
      groups obtained in the similarity dendrogram, based on phenotypic
      characteristics, had their 16S rRNA genes sequenced. The legume species showed
      nodules with indeterminate growth, and reddish color, distributed throughout the
      root. Fifty-one strains of these nodules were isolated, of which 21 were
      classified in the genus Bacillus, Brevibacillus, Paenibacillus, Rhizobium and
      especially Sinorhizobium. Strains closely related to Sinorhizobium adhaerens were
      the predominant bacteria in nodules. The other genera found, with the exception
      of Rhizobium, are probably endophytic bacteria in the nodules. Arbuscular
      mycorrhizal fungi was observed colonizing the roots, but arbuscular mycorhizal
      fungi spores were not found in the trap cultures. Therefore Sophora tomentosa is
      associated with both arbuscular mycorhizal fungi and nodulating nitrogen-fixing
      bacteria.

PMID- 28756032
TI  - Corrigendum to "Imperatorin exerts antiallergic effects in Th2-mediated allergic
      asthma via induction of IL-10-producing regulatory T cells by modulating the
      function of dendritic cells" [Pharmacol. Res. (2016) 111-121].

PMID- 28756033
TI  - Should patients with traumatic out-of-hospital cardiac arrest be transferred?

PMID- 28756034
TI  - Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A
      meta-analysis.
AB  - BACKGROUND: The benefits and adverse effects of corticosteroids in the treatment
      of severe community-acquired pneumonia (CAP) have not been well assessed. The aim
      of this systematic review of the literature and meta-analysis was to evaluate the
      clinical efficacy of adjuvant corticosteroid therapy in patients with severe CAP.
      METHODS: The following databases were searched: PubMed, the Cochrane database,
      Embase, Wanfang, the China National Knowledge Infrastructure (CNKI), and the
      WeiPu (VIP) database in Chinese. Published randomized controlled clinical trial
      results were identified that compared corticosteroid therapy with conventional
      therapy for patients with severe CAP, up to November 2016. The relative risk
      (RR), weighted mean difference (WMD), and 95% confidence interval (CI) were
      evaluated. Statistical analysis was performed using STATA 10.0. The quality of
      the published studies was evaluated using the Oxford quality scoring system
      (Jadad scale). RESULTS: Ten randomized controlled trials (RCTs) were identified
      that included 729 patients with severe CAP. Data analysis showed that
      corticosteroid therapy did not have a statistically significant clinical effect
      in patients with severe CAP (RR: 1.19; 95% CI: 0.99-1.42), mechanical ventilation
      time (WMD: -2.30; 95% CI: -6.09-1.49). However, corticosteroids treatment was
      significantly associated with reduced in-hospital mortality (RR: 0.49; 95% CI:
      0.29-0.85), reduced length of hospital stay (WMD: -4.21; 95% CI: -6.61 to -1.81).
      CONCLUSION: Corticosteroids adjuvant therapy in patients with severe CAP may
      reduce the rate of in-hospital mortality, reduce the length of hospital stay, and
      reduce CRP levels.

PMID- 28756035
TI  - Role of clinical suspicion in pediatric blunt trauma patients with severe
      mechanisms of injury.
AB  - OBJECTIVES: In adult patients with blunt trauma, severe mechanism of injury leads
      to routine pan-computed tomography (CT). Due to concerns about the risk of
      radiation, we sought to determine whether clinical suspicion could identify
      children requiring radiographic imaging. METHODS: A prospective study was
      conducted in a pediatric emergency department of a Level 1 trauma center.
      Patients <=14years presenting with blunt trauma due to predefined severe
      mechanisms were eligible. Physicians recorded their suspicions for clinically
      significant injury (CSI). Imaging was obtained at the physician's discretion. CSI
      was defined as injury requiring intervention or hospital admission >=24h. Both
      admitted and discharged patients were contacted >=2weeks after presentation to
      document undetected injuries. RESULTS: 837 patients were eligible; 753 were
      enrolled. 159 patients were excluded because the mechanism did not meet severity
      criteria. Follow-up was completed for 529/594 remaining patients. Physicians were
      suspicious of all injuries in 71/75 patients with CSI and had no suspicions in
      382/454 without CSI. The 75 injured patients had 153 CSIs; positive suspicion of
      CSI was recorded for 149 injuries. The four patients who sustained unsuspected
      injuries had multiple other suspected injuries. Of the 594 patients, 42 received
      focused CT and 14 underwent pan-CT. No patient had previously undetected injuries
      on follow-up. CONCLUSION: In our study, clinical suspicion was able to identify
      children with CSI. If further studies support our findings, using clinical
      suspicion rather than mechanism alone to guide radiographic imaging may avoid
      unnecessary radiation exposure.

PMID- 28756036
TI  - Spontaneous rupture of the iliac vein.
AB  - Spontaneous iliac vein rupture is a rare diagnosis with less than 40 cases
      documented worldwide. There are certain similarities between many of the
      previously reported cases described in the literature and there are various
      proposed theories as to why patients develop a spontaneous rupture. A delay in
      diagnosis is not uncommon and the mainstay of treatment is laparotomy. Here, we
      report a case of a 51-year-old female with lower extremity swelling for 2days who
      subsequently developed hemorrhagic shock and had to be taken emergently to
      surgery, where a rupture of the common and external iliac veins was identified.
      After multiple blood products, vasopressors, and continuous renal replacement
      therapy the patient expired on day 3 of hospitalization.

PMID- 28756037
TI  - Value of a national administrative database to guide public decisions: From the
      systeme national d'information interregimes de l'Assurance Maladie (SNIIRAM) to
      the systeme national des donnees de sante (SNDS) in France.
AB  - In 1999, French legislators asked health insurance funds to develop a systeme
      national d'information interregimes de l'Assurance Maladie (SNIIRAM) [national
      health insurance information system] in order to more precisely determine and
      evaluate health care utilization and health care expenditure of beneficiaries.
      These data, based on almost 66 million inhabitants in 2015, have already been the
      subject of numerous international publications on various topics: prevalence and
      incidence of diseases, patient care pathways, health status and health care
      utilization of specific populations, real-life use of drugs, assessment of
      adverse effects of drugs or other health care procedures, monitoring of national
      health insurance expenditure, etc. SNIIRAM comprises individual information on
      the sociodemographic and medical characteristics of beneficiaries and all
      hospital care and office medicine reimbursements, coded according to various
      systems. Access to data is controlled by permissions dependent on the type of
      data requested or used, their temporality and the researcher's status. In
      general, data can be analyzed by accredited agencies over a period covering the
      last three years plus the current year, and specific requests can be submitted to
      extract data over longer periods. A 1/97th random sample of SNIIRAM, the
      echantillon generaliste des beneficiaires (EGB), representative of the national
      population of health insurance beneficiaries, was composed in 2005 to allow 20
      year follow-up with facilitated access for medical research. The EGB is an open
      cohort, which includes new beneficiaries and newborn infants. SNIIRAM has
      continued to grow and extend to become, in 2016, the cornerstone of the future
      systeme national des donnees de sante (SNDS) [national health data system], which
      will gradually integrate new information (causes of death, social and medical
      data and complementary health insurance). In parallel, the modalities of data
      access and protection systems have also evolved. This article describes the
      SNIIRAM data warehouse and its transformation into SNDS, the data collected, the
      tools developed in order to facilitate data analysis, the limitations
      encountered, and changing access permissions.

PMID- 28756038
TI  - Association between glycemic load and cognitive function in community-dwelling
      older adults: Results from the Brain in Motion study.
AB  - BACKGROUND: Impaired glucose tolerance is a risk factor for non-age-related
      cognitive decline and is also associated with measures of physical activity (PA)
      and cardiorespiratory fitness (CRF). A low glycemic load (GL) diet can aid in the
      management of blood glucose levels, but little is known about its effect on
      cognition with poor glucoregulation. OBJECTIVE: We assessed the relation between
      GL and cognitive function by glucoregulation and possible mediatory effects by
      CRF and PA in older adults from the Brain in Motion Study. DESIGN: A cross
      sectional analysis of 194 cognitively healthy adults aged >=55 years (mean =
      65.7, SD = 6.1) was conducted. GL was assessed using a quantitative food
      frequency questionnaire, and glucoregulation was characterized on the HOMA-IR
      index. Subjects also completed a cognitive assessment, CRF testing, a validated
      self-reported PA questionnaire, and a blood draw. Multiple linear regression
      models adjusted for significant covariates were used to evaluate the relation
      between GL and cognition, and mediation by CRF and PA was also assessed. RESULTS:
      GL was inversely associated with global cognition (beta = -0.014; 95% CI -0.024, 
      0.004) and figural memory (beta = -0.035; 95% CI -0.052, -0.018) in subjects with
      poor glucoregulation. Neither CRF nor PA mediated these relations. In subjects
      with good glucoregulation, no association was found between GL and cognitive
      function (p > 0.05). CONCLUSIONS: A low GL diet is associated with better
      cognitive function in older adults with poor glucoregulation. This study provides
      supportive evidence for the role of GL in maintaining better cognitive function
      during the aging process.

PMID- 28756039
TI  - Muscle wasting and survival following pre-operative chemoradiotherapy for locally
      advanced rectal carcinoma.
AB  - BACKGROUND & AIMS: Neoadjuvant chemoradiotherapy (NACRT) has increased local
      control in locally advanced rectal cancer. Reduced skeletal muscle mass
      (sarcopenia), or ongoing muscle wasting, is associated with decreased survival in
      cancer. This study aims to assess the change in body composition during NACRT and
      its impact on outcome using computed tomography (CT) imaging in locally advanced
      rectal cancer (LARC) patients. METHODS: LARC patients treated with NACRT were
      selected from a prospectively maintained database and retrospectively analyzed.
      One-hundred twenty-two patients who received treatment between 2004 and 2012 with
      available diagnostic CT imaging obtained before and after NACRT were identified.
      Cross-sectional areas for skeletal muscle was determined, and subsequently
      normalized for patient height. Differences between skeletal muscle areas before
      and after NACRT were computed, and their influence on overall and disease-free
      survival was assessed. RESULTS: A wide distribution in change of body composition
      was observed. Loss of skeletal muscle mass during chemoradiotherapy was
      independently associated with disease-free survival (HR0.971; 95% CI: 0.946
      0.996; p = 0.025) and distant metastasis-free survival (HR0.942; 95% CI: 0.898
      0.988; p = 0.013). No relation was observed with overall survival in the current
      cohort. CONCLUSIONS: Loss of skeletal muscle mass during NACRT in rectal cancer
      patients is an independent prognostic factor for disease-free survival and
      distant metastasis-free survival following curative intent resection.

PMID- 28756040
TI  - Viscoelastic parameter identification of human brain tissue.
AB  - Understanding the constitutive behavior of the human brain is critical to
      interpret the physical environment during neurodevelopment, neurosurgery, and
      neurodegeneration. A wide variety of constitutive models has been proposed to
      characterize the brain at different temporal and spatial scales. Yet, their model
      parameters are typically calibrated with a single loading mode and fail to
      predict the behavior under arbitrary loading conditions. Here we used a finite
      viscoelastic Ogden model with six material parameters-an elastic stiffness, two
      viscoelastic stiffnesses, a nonlinearity parameter, and two viscous time
      constants-to model the characteristic nonlinearity, conditioning, hysteresis and
      tension-compression asymmetry of the human brain. We calibrated the model under
      shear, shear relaxation, compression, compression relaxation, and tension for
      four different regions of the human brain, the cortex, basal ganglia, corona
      radiata, and corpus callosum. Strikingly, unconditioned gray matter with 0.36kPa
      and white matter with 0.35kPa were equally stiff, whereas conditioned gray matter
      with 0.52kPa was three times stiffer than white matter with 0.18kPa. While both
      unconditioned viscous time constants were larger in gray than in white matter,
      both conditioned constants were smaller. These rheological differences suggest a
      different porosity between both tissues and explain-at least in part-the ongoing
      controversy between reported stiffness differences in gray and white matter. Our
      unconditioned and conditioned parameter sets are readily available for finite
      element simulations with commercial software packages that feature Ogden type
      models at finite deformations. As such, our results have direct implications on
      improving the accuracy of human brain simulations in health and disease.

PMID- 28756041
TI  - Positive and negative affect following marijuana use in naturalistic settings: An
      ecological momentary assessment study.

PMID- 28756042
TI  - Effectiveness of continuing nicotine replacement after a lapse: A randomized
      trial.
AB  - INTRODUCTION: Four post-hoc analyses of prior trials found smokers using nicotine
      patch following a lapse were less likely to progress to relapse compared to those
      using a placebo patch following a lapse. We attempted a conceptual replication
      test of these results via a randomized trial of instructions to continue vs. stop
      nicotine patch after a lapse. METHODS: Smokers trying to quit (n=701) received
      nicotine patch (21/14/7mg) and brief phone counseling (six 15-min sessions). We
      randomized smokers to receive instructions for and rationale for stopping vs.
      continuing patch after a lapse. The messages were repeated before and after
      cessation and following lapses via counseling, phone and written instructions.
      RESULTS: Among those who lapsed, those told to Continue Patch did not have a
      greater incidence of 7-day abstinence at 4months (primary outcome) than those
      told to Discontinue Patch (51% vs. 46%). Most (81%) participants in the
      Discontinue condition stopped patch for only 1-2days and then resumed abstinence
      and patch use. Analyses based on all participants randomized were similar.
      Adverse events were as expected and did not differ between conditions.
      CONCLUSION: Instructions to continue nicotine patch after a lapse did not
      increase return to abstinence. These negative results may have occurred because
      actual use of patch after a lapse was similar in the two conditions. Also,
      allowing patch use while smoking may have reduced motivation to stay abstinent.

PMID- 28756043
TI  - Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage
      and healing in patients with chronic limb-threatening ischemia.
AB  - BACKGROUND: Direct (DIR) or indirect (IND) revascularization of pedal angiosomes
      in patients with chronic limb-threatening ischemia (CLTI) has an unclear impact
      on limb salvage and healing. The aim of this study was to evaluate the outcomes
      of DIR and IND revascularization in patients with a peroneal bypass and tissue
      loss. METHODS: We conducted a retrospective study of a prospectively maintained
      database in two European university centers from 2004 to 2015. We extracted from
      this database all patients with CLTI and tissue loss who had received a bypass to
      the peroneal artery. All patients underwent angiography before bypass.
      Revascularization was considered DIR if the wound was in a peroneal angiosome.
      Wounds, ischemia, and infection were categorized according to the Wound,
      Ischemia, and foot Infection (WIfI) classification. Limb salvage and amputation
      free survival were calculated using the Kaplan-Meier method. Cox regression was
      used to compare the role of patient characteristics, including diabetes, peroneal
      runoff, pedal arch angiosome, WIfI grade, chronic kidney disease, and diabetes,
      in amputation-free-survival. RESULTS: From January 2004 through October 2015,
      there were 120 peroneal bypasses performed in 120 patients with CLTI and foot
      tissue loss. Only 55 wounds (46%) could be ascribed to a peroneal angiosome. At 3
      years, amputation-free survival in patients with DIR revascularization was 54.9%
      +/- 7.3% compared with 56.5% +/- 6.3% in patients with IND revascularization (P =
      .44), with no significant difference in wound healing. Amputation-free survival
      at 3 years in patients with two patent peroneal branches was 74.8% +/- 6.9%
      compared with 45.0% +/- 6.0% in patients with one patent peroneal branch (P =
      .003). Amputation-free survival at 3 years in patients with a patent pedal arch
      (Rutherford 0-1) was 73.0% +/- 7.0% vs 45.7% +/- 6.0% in patients with incomplete
      pedal arch (Rutherford 2-3; P = .0002). Amputation-free survival at 3 years in
      patients with grade 1 or grade 2 WIfI was 87.4% +/- 8.3% compared with 48.4% +/-
      5.3% in patients with grade 3 or grade 4 WIfI (P = .001). Amputation-free
      survival at 3 years in patients with diabetes was 43.7% +/- 6.2% compared with
      73.1% +/- 6.7% in patients without diabetes (P = .002). Wound healing at 6 months
      was not significantly improved by its location within or outside a peroneal
      angiosome. Cox regression analysis demonstrated that diabetes, patency of both
      peroneal branches, patency of pedal arch, and WIfI stage but not DIR angiosome
      revascularization were significant predictors of amputation-free survival.
      CONCLUSIONS: Our results suggest that in patients with CLTI and tissue loss
      receiving a peroneal bypass, patency of both peroneal branches and pedal arch was
      associated with a better healing rate and a better amputation-free survival rate
      irrespective of wound angiosome location.

PMID- 28756044
TI  - Association between arterial stiffness and peripheral artery disease as measured
      by radial artery tonometry.
AB  - OBJECTIVE: Arterial stiffness and peripheral artery disease (PAD) are both
      associated with an elevated risk of major adverse cardiac events; however, the
      association between arterial stiffness and PAD is less well characterized. The
      goal of this study was to examine the association between parameters of radial
      artery tonometry, a noninvasive measure of arterial stiffness, and PAD. METHODS:
      We conducted a cross-sectional study of 134 vascular surgery outpatients
      (controls, 33; PAD, 101) using arterial applanation tonometry. Central
      augmentation index (AIX) normalized to 75 beats/min and peripheral AIX were
      measured using radial artery pulse wave analysis. Pulse wave velocity was
      recorded at the carotid and femoral arteries. PAD was defined as symptomatic
      claudication with an ankle-brachial index of <0.9 or a history of peripheral
      revascularization. Controls had no history of atherosclerotic vascular disease
      and an ankle-brachial index >=0.9. RESULTS: Among the 126 participants with high
      quality tonometry data, compared with controls (n = 33), patients with PAD (n =
      93) were older, with higher rates of hypertension, hyperlipidemia, diabetes, and
      smoking (P < .05). Patients with PAD also had greater arterial stiffness as
      measured by central AIX, peripheral AIX, and pulse wave velocity (P < .05). In a
      multivariable model, a significantly increased odds of PAD was associated with
      each 10-unit increase in central AIX (odds ratio, 2.1; 95% confidence interval,
      1.1-3.9; P = .03) and peripheral AIX (odds ratio, 1.9; 95% confidence interval,
      1.2-3.2; P = .01). In addition, central and peripheral AIX were highly correlated
      (r120 = 0.76; P < .001). CONCLUSIONS: In a cross-sectional analysis, arterial
      stiffness as measured by the AIX is independently associated with PAD, even when
      adjusting for several atherosclerotic risk factors. Further prospective data are
      needed to establish whether radial artery tonometry could be a tool for risk
      stratification in the PAD population.

PMID- 28756045
TI  - Increasing use of endovascular therapy in pediatric arterial trauma.
AB  - BACKGROUND: Endovascular therapy has been increasingly used for critically
      injured adults. However, little is known about the epidemiology and outcomes of
      endovascularly managed arterial injuries in children. We therefore aimed to
      evaluate recent trends in the endovascular management of pediatric arterial
      injuries and its association with early survival. METHODS: An 8-year analysis of
      the National Trauma Databank (2007-2014) was performed to extract all pediatric
      trauma patients (aged <=16 years) with arterial injuries. Demographics, clinical
      data, interventions (endovascular vs open), and outcomes (in-hospital mortality
      and length of stay) were extracted. Patients undergoing endovascular or open
      procedures were compared for differences in clinical characteristics using
      bivariate analysis. Multivariable logistic regression analysis quantified the
      association between endovascular therapy and survival in the context of other
      variables predictive of survival on univariate analysis, with alpha <= .05.
      RESULTS: There were 35,771 pediatric patients available for analysis. Overall,
      there was a significant increase in the use of endovascular procedures (from 7.8%
      in 2007 to 12.9% in 2014; P < .001), particularly among blunt trauma patients
      (5.8% in 2007 to 15.7% in 2014; P < .001). Conversely, a significant decrease was
      noted for open procedures (P < .001). There was a stepwise increase in the
      proportion of patients managed endovascularly as the Injury Severity Score (ISS)
      increased (highest in the ISS spectrum of 31-50). Angioembolization of internal
      iliac injury and thoracic aortic endograft placement were the two most common
      endovascular procedures (n = 88 [33.4%] and n = 60 [22.9%], respectively). There
      were 331 decedents (9.1% vascular injured children), 242 (73.1%) of whom were
      dead on arrival. After controlling for differences in demographics and clinical
      data, when outcomes were compared between patients who underwent endovascular and
      open procedures, there were no significant differences regarding in-hospital
      mortality (3.0% vs 3.6%; odds ratio, 0.7; 95% confidence interval, 0.1-6.1; P =
      .778). A logistic regression model identified Glasgow Coma Scale score <=8, ISS
      >=16, positive result of ethanol or drug screen, and systolic blood pressure <90
      mm Hg on admission as independent risk factors for death. CONCLUSIONS: The use of
      endovascular therapy in pediatric vascular arterial trauma has significantly
      increased, especially among severely injured blunt trauma patients. Despite this
      successful integration into care, there was no in-hospital survival advantage
      conferred by endovascular therapy compared with traditional open therapy.
      Approximately 10% of children with arterial injuries died during initial trauma
      assessment before therapy could be offered. Glasgow Coma Scale score <=8, ISS
      >=16, positive result of ethanol or drug screen, and systolic blood pressure <90
      mm Hg on admission were identified as independent risk factors for death. As
      children are a population of vulnerable patients, long-term, multicenter studies
      are required to determine the most appropriate use of and indications for
      endovascular therapy in pediatric arterial trauma.

PMID- 28756046
TI  - A preoperative risk score for transfusion in infrarenal endovascular aneurysm
      repair to avoid type and cross.
AB  - OBJECTIVE: Preoperative type and cross are often routinely ordered before
      elective endovascular aneurysm repair (EVAR), but the cost of this practice is
      high, and transfusion is rare. We therefore aimed to stratify patients by their
      risk of transfusion to identify a cohort in whom a type and screen would be
      sufficient. METHODS: We queried the targeted vascular module of the National
      Surgical Quality Improvement Program (NSQIP) for all elective EVARs from 2011 to
      2015. We included only infrarenal aneurysms and excluded ruptured aneurysms and
      patients transfused within 72 hours preoperatively. Two-thirds of the cases were
      randomly assigned to a model derivation cohort and one third to a validation
      cohort. We created and subsequently validated a risk model for transfusion within
      the first 24 hours of surgery (including intraoperatively), using logistic
      regression. RESULTS: Between 2011 and 2015, there were 4875 patients who
      underwent elective infrarenal EVAR, only 221 (4.5%) of whom received a
      transfusion within 24 hours of surgery. The frequency of transfusion during the
      study period declined monotonously from 6.5% in 2011 to 3.2% in 2015. The factors
      independently associated with transfusion were preoperative hematocrit <36% (odds
      ratio [OR], 3.4 [95% confidence interval, 2.1-5.4]; P < .001), aortic diameter
      (per centimeter increase: OR, 1.2 [1.03-1.4]; P = .02), preoperative dependent
      functional status (OR, 2.5 [1.1-5.5]; P = .03), and chronic obstructive pulmonary
      disease (OR, 1.7 [1.04-2.9]; P = .04). A risk prediction model based on these
      criteria produced a C statistic of 0.69 in the prediction cohort and 0.76 in the
      validation cohort and a Hosmer-Lemeshow goodness of fit of 0.62 and 0.14,
      respectively. A score of <3 of 9, corresponding to a <5% probability of
      transfusion, would avoid preoperative type and cross in 86% of patients. Of the
      4203 patients (86%) with a hematocrit >36%, only 6 (0.1%) had a risk score of >3.
      CONCLUSIONS: Perioperative transfusion for EVAR is becoming increasingly uncommon
      and is predicted well by a transfusion risk score or simply a hematocrit of <36%.
      Application of this risk score would avoid unnecessary type and cross in the
      majority of patients, leading to significant savings in both time and cost.

PMID- 28756047
TI  - Effectiveness of surgical interventions for thoracic aortic aneurysms: A
      systematic review and meta-analysis.
AB  - OBJECTIVE: A systematic review and meta-analysis was conducted to evaluate the
      effectiveness of thoracic endovascular aortic repair (TEVAR) and open repair in
      patients with descending thoracic aortic aneurysms (TAAs). METHODS: PubMed, Ovid
      MEDLINE, Ovid Embase, EBSCO Cumulative Index to Nursing and Allied Health
      Literature, and Scopus were searched from each database's inception to January
      29, 2016. We selected studies that compared the two approaches in adults with
      TAAs and reported 30-day mortality or procedure complications. Two reviewers
      independently extracted data, and conflicts were resolved by consensus. Random
      effects meta-analysis was used to estimate odds ratios (ORs) and 95% confidence
      intervals (CIs). The main outcomes and measures were all-cause 30-day mortality,
      30-day paraplegia or spinal cord ischemia, stroke, pulmonary complications, and
      length of hospital and intensive care unit (ICU) stay. RESULTS: Twenty-seven
      studies of moderate methodologic quality were included. TEVAR was associated with
      lower 30-day mortality in ruptured (OR, 0.58; 95% CI, 0.38-0.88) and intact (OR,
      0.6; 95% CI, 0.36-0.99) aneurysms. Paraplegia or spinal cord ischemia (OR, 0.35;
      95% CI, 0.2-0.61) and pulmonary complications (OR, 0.41; 95% CI, 0.37-0.46) were
      reduced in patients undergoing TEVAR, whereas a reduction in stroke risk was not
      statistically significant (OR, 0.89; 95% CI, 0.76-1.03). Pooled mean difference
      in length of hospital and ICU stay was lower for TEVAR by -5.17 days (95% CI, 
      7.77 to -2.57) and -5.89 days (95% CI, -9.65 to -2.12), respectively. Three
      studies showed that compared with open repair, a hybrid approach reduced hospital
      stay (pooled mean difference, -8.83 days; 95% CI, -14.37 to -3.29) and ICU stay
      (pooled mean difference, -3.17 days (95% CI, -5.54 to -0.97), with minimal
      evidence on other outcomes studied. CONCLUSIONS: Observational evidence at high
      risk of confounding suggests that compared with open repair for TAA, TEVAR
      reduced risk of mortality, paraplegia, spinal cord ischemia, and pulmonary
      complications within 30 days of intervention. Patients undergoing TEVAR also had
      shorter length of hospital and ICU stay compared with patients undergoing open
      repair.

PMID- 28756048
TI  - Frailty Assessments in Surgical Practice: What is Frailty and How Can It Be Used
      in Prosthetic Health?
AB  - INTRODUCTION: Surgical frailty is a previously unrecognized clinical entity that
      objectifies a multiorgan decrease in physiologic reserve in those undergoing
      surgery. Although penile implantation has been demonstrated to be an effective
      means of restoring erectile function in patients whose previous conservative
      measures have failed, there are limited data regarding the assessment of frailty
      in patients undergoing penile implantation. AIM: To review the various objective
      methods used to describe surgical frailty in medical and surgical disciplines,
      report on methodologies of frailty assessment, and discuss the relevance of
      surgical frailty in the preoperative evaluation of patients undergoing
      implantation of an inflatable penile prosthesis. METHODS: A literature review was
      performed through PubMed regarding surgical frailty in the disciplines of
      medicine, surgery, and urology. Key words and phrases included frailty, elderly,
      aging, erectile dysfunction, penile implantation, and penile prosthesis. MAIN
      OUTCOME MEASURE: Critical assessment of frailty in medicine and its application
      to male prosthetic health. RESULTS: Frailty has been assessed by different
      metrics in multiple fields. Validated modalities to determine physiologic reserve
      include an accumulation of deficits and phenotypic objective assessments that are
      reviewed in detail. Frail patients experience longer length of stay,
      postoperative complications, unplanned returns to the operating room, and
      readmissions and are less likely to be discharged to home. Novel frailty
      assessments objectified through grip strength measurements from our institution
      demonstrate that a considerable number of patients, young and old, undergoing
      penile implantation exhibit surgical frailty. CONCLUSION: There is a growing need
      to incorporate frailty assessment in the preoperative risk stratification of
      patients undergoing penile implantation. Grip strength evaluation seems to be an
      obvious standard because it is likely the easiest to measure and is clinically
      relevant given the user's dependence on manual dexterity to use the device.
      Screening for frailty does not create a substantial time, financial, or resource
      burden for the urologist. Brennan MS, Barlotta RM, Simhan J. Frailty Assessments
      in Surgical Practice: What is Frailty and How Can It Be Used in Prosthetic
      Health? Sex Med Rev 2018;6:302-309.

PMID- 28756049
TI  - Sociodemographic and lifestyle factors as determinants of energy intake and
      macronutrient composition: a 10-year follow-up after bariatric surgery.
AB  - BACKGROUND: Early identification of the potential to adopt a long-term unhealthy
      diet, could improve weight outcomes for patients having undergone bariatric
      surgery. OBJECTIVES: We explored whether presurgical sociodemographic and
      lifestyle characteristics, together with the type of surgery, could predict 10
      year changes in dietary intake after bariatric surgery. SETTING: Surgical
      departments and primary healthcare centers, nationwide. METHODS: Participants
      were from the Swedish Obese Subjects study, a matched (nonrandomized) prospective
      trial comparing bariatric surgery with standard care for obese patients. This
      study included the 1695 surgery patients with complete information on presurgery
      diet. Questionnaires were completed before and 6 months, 1-4, 6, 8, and 10 years
      after surgery. Analyses were conducted with linear mixed-model. RESULTS: Dietary
      changes were observed in 1561, 1298, and 1243 participants, at the 2-, 6-, and 10
      year follow-ups, respectively. Sex and treatment type predicted changes in
      energy, carbohydrate, protein, and fiber intake over the follow-up (P<.05).
      Furthermore, male sex, younger age, a sedentary behavior, and gastric bypass
      predicted increased alcohol consumption (P<.001). Two important phases for
      intervening bariatric patients' diet were identified. The first was 6 months
      after surgery, when the maximal changes in diet were achieved. The second,
      stretched from 6 months until 4 years after surgery, during which earlier
      commitments to dietary changes were largely abandoned. CONCLUSIONS: Male sex and
      banding surgery in particular predicted unfavorable post-surgery changes in
      energy and macronutrient intake. Furthermore, gastric bypass, a younger age, and
      an unhealthy lifestyle presurgery, may predispose individuals to increased
      alcohol intake after surgery.

PMID- 28756050
TI  - Bile acid profiles over 5 years after gastric bypass and duodenal switch: results
      from a randomized clinical trial.
AB  - BACKGROUND: Bile acids have been proposed as key mediators of the metabolic
      effects after bariatric surgery. Currently no reports on bile acid profiles after
      duodenal switch exist, and long-term data after gastric bypass are lacking.
      OBJECTIVE: To investigate bile acid profiles up to 5 years after Roux-en-Y
      gastric bypass and biliopancreatic diversion with duodenal switch and to explore
      the relationship among bile acids and weight loss, lipid profile, and glucose
      metabolism. SETTINGS: Two Scandinavian University Hospitals. METHODS: We present
      data from a randomized clinical trial of 60 patients with body mass index 50-60
      kg/m2 operated with gastric bypass or duodenal switch. Repeated measurements of
      total and individual bile acids from fasting serum during 5 years after surgery
      were performed. RESULTS: Mean concentrations of total bile acids increased from
      2.3 umol/L (95% confidence interval [CI], -.1 to 4.7) at baseline to 5.9 umol/L
      (3.5-8.3) 5 years after gastric bypass and from 1.0 umol/L (95% CI, -1.4 to 3.5)
      to 9.5 umol/L (95% CI, 7.1-11.9) after duodenal switch; mean between-group
      difference was -4.8 umol/L (95% CI, -9.3 to -.3), P = .036. Mean concentrations
      of primary bile acids increased more after duodenal switch, whereas secondary
      bile acids increased proportionally across the groups. Higher levels of total
      bile acids at 5 years were associated with lower body mass index, greater weight
      loss, and lower total cholesterol. CONCLUSIONS: Total bile acid concentrations
      increased substantially over 5 years after both gastric bypass and duodenal
      switch, with greater increases in total and primary bile acids after duodenal
      switch. (Surg Obes Relat Dis 2017;0:000-000.) (c) 2017 American Society for
      Metabolic and Bariatric Surgery. All rights reserved.

PMID- 28756051
TI  - Identifying the Optimal Radiation Dose in Locally Advanced Non-Small-cell Lung
      Cancer Treated With Definitive Radiotherapy Without Concurrent Chemotherapy.
AB  - INTRODUCTION: The optimal radiation dose for locally advanced non-small-cell lung
      cancer (NSCLC) is not known for patients who receive sequential chemoradiation
      (CRT) or definitive radiotherapy (RT) only. Our objective was to determine
      whether a benefit exists for radiation dose escalation for these patients.
      MATERIALS AND METHODS: The patients included in our retrospective analysis had
      undergone RT for NSCLC from 2004 to 2013, had not undergone surgery, and received
      a dose >= 50.0 Gy. Patients who received concurrent CRT were excluded from the
      analysis, leaving 336 patients for analysis. The primary outcomes were overall
      survival (OS), local failure (LF), and distant failure (DF). RESULTS: On
      multivariate analysis, after adjusting for age, Karnofsky performance status,
      gross tumor volume, and treatment modality, patients treated with a radiation
      dose > 66 Gy had significantly improved OS compared with those treated with < 60
      Gy (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.39-0.87; P = .008).
      After adjusting for smoking history and radiologic tumor size, patients treated
      with a radiation dose > 66 Gy had a significantly decreased risk of LF compared
      with those treated with < 60 Gy (HR, 0.59; 95% CI, 0.38-0.91; P = .02). The
      radiation dose was not an independent prognostic factor of DF on multivariate
      analysis. CONCLUSION: When controlling for tumor volume and/or dimensions and
      other independent prognostic factors, patients with locally advanced NSCLC who
      were not candidates for concurrent CRT benefited from a radiation dose > 66 Gy
      versus < 60 Gy with improved OS and reduced LF. An increased radiation dose did
      not appear to affect the incidence of DF.

PMID- 28756052
TI  - Proceedings of a Parent Project Muscular Dystrophy Bone Health Workshop:
      Morbidity due to osteoporosis in DMD: The Path Forward May 12-13, 2016, Bethesda,
      Maryland, USA.

PMID- 28756054
TI  - Bile Duct Mass Determined to Be Eosinophilic Cholangitis by Digital
      Cholangioscopy.

PMID- 28756053
TI  - Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis Frequently
      Have Subclinical Inflammation in the Proximal Colon.
AB  - BACKGROUND & AIMS: Patients with primary sclerosing cholangitis (PSC) and
      ulcerative colitis (UC) have a high risk of colonic neoplasia. Neoplasia
      frequently develops in the proximal colon in patients with PSC. Histologic
      inflammation is an independent risk factor for the development of neoplasia; we
      investigated whether patients with UC and PSC have more subclinical disease
      activity than patients with UC alone. METHODS: We performed a retrospective
      analysis of data from 143 patients (205 examinations) with ulcerative pancolitis
      who were in clinical remission and treated at a tertiary medical center from May
      2011 through May 2016. Endoscopic and histologic activity were compared between
      patients with PSC (from 36 examinations) and without PSC (from 169 examinations).
      Disease activity was scored per colonic segment using a modified Mayo endoscopic
      subscore and histologic assessment. In each colonic segment, differences in
      disease activity and the degree of discordance between endoscopic and histologic
      inflammation among UC patients with and without PSC were compared. RESULTS:
      Patients with UC-PSC had significantly more subclinical endoscopic (odds ratio
      [OR], 4.21; 95% CI, 1.67-10.63) and histologic activity (OR, 5.13; 95% CI, 2.25
      11.68) in the right colon, as well as greater degree of histologic than
      endoscopic inflammation in the proximal colon (OR, 3.14, 95% CI, 1.24-7.97),
      compared with patients without PSC. Patients with UC-PSC had significantly less
      histologic activity in the rectum on multivariate analysis (OR, 0.24; 95% CI,
      0.08-0.72). CONCLUSIONS: Patients with UC and PSC who are in clinical remission
      are significantly more likely to have endoscopic and histologic inflammation in
      the right colon than patients with UC without PSC. Our findings provide insight
      into cause of colorectal cancer in UC patients with PSC.

PMID- 28756055
TI  - Efficacy of Over-the-Scope Clips in Management of High-Risk Gastrointestinal
      Bleeding.
AB  - BACKGROUND & AIMS: Standard endoscopic therapies do not control bleeding or
      produce complications in as many as 20% of patients with nonvariceal
      gastrointestinal bleeding. Most bleeding comes from ulcers with characteristics
      such as high-risk vascular territories and/or large vessels. We evaluated the
      efficacy of using over-the-scope clips (OTSCs) as primary or rescue therapy for
      patients with bleeding from lesions that have a high risk for adverse outcomes.
      METHODS: We performed a retrospective analysis of data from 67 patients with
      gastrointestinal bleeding from high-risk lesions who were treated with OTSCs as
      primary (n = 49) or rescue therapy (n = 18) at a quaternary center, from December
      2011 through February 2015. The definition of high-risk lesions was lesions that
      were situated in the area of a major artery and larger than 2 mm in diameter
      and/or a deep penetrating, excavated, fibrotic ulcer with high-risk stigmata, in
      which a perforation could not be ruled out or thermal therapy would cause
      perforation, or lesions that could not be treated by standard endoscopy. Clinical
      severity was determined based on the Rockall score and a modified Blatchford
      score. Our primary outcome was the incidence of rebleeding within 30 days after
      OTSC placement. We assessed risk factors for rebleeding using univariate hazard
      models followed by multivariable analysis. RESULTS: Of the 67 patients, 47
      (70.1%) remained free of rebleeding at 30 days after OTSC placement. We found no
      difference in the proportion of patients with rebleeding who received primary or
      rescue therapy (hazard ratio, 0.639; 95% confidence interval, 0.084-4.860; P =
      .6653). Only 9 rebleeding events were linked clearly to OTSCs and required
      intervention, indicating an OTSC success rate of 81.3%. We found no significant
      associations between rebleeding and clinical scores. However, on multivariable
      analysis, patients with coronary artery disease had a higher risk of rebleeding
      after OTSC independent of international normalized ratio and antiplatelet use
      (hazard ratio, 7.30; P = .0002). CONCLUSIONS: In a retrospective analysis of 67
      patients with bleeding from high-risk gastrointestinal lesions, we found OTSCs to
      prevent rebleeding in more than 80% of cases. In the past, these lesions were
      treated with surgical or radiologic interventions. Patients with coronary artery
      disease have an increased risk of rebleeding after OTSCs, suggesting the need for
      escalated therapies.

PMID- 28756057
TI  - Rectal Diverticula in an Infant.

PMID- 28756056
TI  - Healthcare Costs Related to Treatment of Hepatocellular Carcinoma Among Veterans
      With Cirrhosis in the United States.
AB  - BACKGROUND & AIMS: It is important to quantify medical costs associated with
      hepatocellular carcinoma (HCC), the incidence of which is rapidly increasing in
      the United States, for development of rational healthcare policies related to
      liver cancer surveillance and treatment of chronic liver disease. We aimed to
      comprehensively quantify healthcare costs for HCC among patients with cirrhosis
      in an integrated health system and develop a model for predicting costs that is
      based on clinically relevant variables. METHODS: Three years subsequent to liver
      cancer diagnosis, costs accrued by patients included in the Veteran's Outcome and
      Cost Associated with Liver disease cohort were compiled by using the Department
      of Veterans Affairs Corporate Data Warehouse. The cohort includes all patients
      with HCC diagnosed in 2008-2010 within the VA with 100% chart confirmation as
      well as chart abstraction of tumor and clinical characteristics. Cancer cases
      were matched 1:4 with non-cancer cirrhosis controls on the basis of severity of
      liver disease, age, and comorbidities to estimate background cirrhosis-related
      costs. Univariable and multivariable generalized linear models were developed and
      used to predict cancer-related overall cost. RESULTS: Our analysis included 3188
      cases of HCC and 12,722 controls. The mean 3-year total cost of care in HCC
      patients was $154,688 (standard error, $150,953-$158,422) compared with $69,010
      (standard error, $67,344-$70,675) in matched cirrhotic controls, yielding an
      incremental cost of $85,679; 64.9% of this value reflected increased inpatient
      costs. In univariable analyses, receipt of transplantation, Barcelona Clinic
      Liver Cancer (BCLC) stage, liver disease etiology, hospital academic affiliation,
      use of multidisciplinary tumor board, and identification through surveillance
      were associated with cancer-related costs. Multivariable generalized linear
      models incorporating transplantation status, BCLC stage, and multidisciplinary
      tumor board presentation accurately predicted liver cancer-related costs (Hosmer
      Lemeshow goodness of fit; P value ? 1.0). CONCLUSIONS: In a model developed to
      comprehensively quantify healthcare costs for HCC among patients with cirrhosis
      in an integrated health system, we associated receipt of liver transplantation,
      BCLC stage, and multidisciplinary tumor board with higher costs. Models that
      predict total costs on the basis of receipt of liver transplantation were
      constructed and can be used to model cost-effectiveness of therapies focused on
      HCC prevention.

PMID- 28756058
TI  - Toward More Efficient Dietary Elimination Therapy for Eosinophilic Esophagitis:
      The Fantastic 4?

PMID- 28756059
TI  - SpineNet: Automated classification and evidence visualization in spinal MRIs.
AB  - The objective of this work is to automatically produce radiological gradings of
      spinal lumbar MRIs and also localize the predicted pathologies. We show that this
      can be achieved via a Convolutional Neural Network (CNN) framework that takes
      intervertebral disc volumes as inputs and is trained only on disc-specific class
      labels. Our contributions are: (i) a CNN architecture that predicts multiple
      gradings at once, and we propose variants of the architecture including using 3D
      convolutions; (ii) showing that this architecture can be trained using a multi
      task loss function without requiring segmentation level annotation; and (iii) a
      localization method that clearly shows pathological regions in the disc volumes.
      We compare three visualization methods for the localization. The network is
      applied to a large corpus of MRI T2 sagittal spinal MRIs (using a standard
      clinical scan protocol) acquired from multiple machines, and is used to
      automatically compute disk and vertebra gradings for each MRI. These are:
      Pfirrmann grading, disc narrowing, upper/lower endplate defects, upper/lower
      marrow changes, spondylolisthesis, and central canal stenosis. We report near
      human performances across the eight gradings, and also visualize the evidence for
      these gradings localized on the original scans.

PMID- 28756060
TI  - Response to letter - Androgen deprivation therapy and cardiovascular risk: No
      meaningful difference between GnRH antagonist and agonists.

PMID- 28756061
TI  - Assessment of acute motor deficit in the pediatric emergency room.
AB  - OBJECTIVES: This review article aimed to present a clinical approach, emphasizing
      the diagnostic investigation, to children and adolescents who present in the
      emergency room with acute-onset muscle weakness. SOURCES: A systematic search was
      performed in PubMed database during April and May 2017, using the following
      search terms in various combinations: "acute," "weakness," "motor deficit,"
      "flaccid paralysis," "child," "pediatric," and "emergency". The articles chosen
      for this review were published over the past ten years, from 1997 through 2017.
      This study assessed the pediatric age range, from 0 to 18 years. SUMMARY OF THE
      DATA: Acute motor deficit is a fairly common presentation in the pediatric
      emergency room. Patients may be categorized as having localized or diffuse motor
      impairment, and a precise description of clinical features is essential in order
      to allow a complete differential diagnosis. The two most common causes of acute
      flaccid paralysis in the pediatric emergency room are Guillain-Barre syndrome and
      transverse myelitis; notwithstanding, other etiologies should be considered, such
      as acute disseminated encephalomyelitis, infectious myelitis, myasthenia gravis,
      stroke, alternating hemiplegia of childhood, periodic paralyses, brainstem
      encephalitis, and functional muscle weakness. Algorithms for acute localized or
      diffuse weakness investigation in the emergency setting are also presented.
      CONCLUSIONS: The clinical skills to obtain a complete history and to perform a
      detailed physical examination are emphasized. An organized, logical, and stepwise
      diagnostic and therapeutic management is essential to eventually restore
      patient's well-being and full health.

PMID- 28756062
TI  - Determining the frequency of morphological characteristics in a sample of
      Brazilian children.
AB  - OBJECTIVE: To establish the frequency of 82 morphological features in a sample of
      Brazilian children (between 3 and 13 years old), to understand the influence of
      age, gender, and ethnicity. METHODS: This was a cross-sectional study that
      evaluated 239 children with typical development (between 3 and 13 years old)
      regarding the presence of 82 morphological characteristics. A previously
      described protocol, based on the London Dysmorphology Database, was applied to
      evaluate the sample. This protocol was culturally adapted to Brazilian
      Portuguese. RESULTS: The frequency of 82 morphological characteristics was
      established in the sample; of 82 characteristics, 50% were considered
      morphological anomalies (frequency less than 4%). At least 25% of the sample
      presented more than one minor morphological anomaly. Age was shown to influence
      the frequency of the following morphological characteristics: widow's peak,
      prominent antihelix, prominent upper lip, irregular or crowded teeth, and
      clinodactyly, but had no influence on the frequency of minor morphological
      anomalies. Gender influenced dysplastic ears and attached earlobe, but had no
      influence on the frequency of minor morphological anomalies; ethnicity showed
      influence on camptodactyly and prominent antihelix. A statistically significant
      divergence was observed regarding 43 of the 73 morphological characteristics that
      could be compared with literature data (58.9%). CONCLUSIONS: The study determined
      the frequency of 82 morphological characteristics in 239 children with typical
      development. Age was the variable that showed more influence on the frequency of
      morphological characteristics, and comparison with literature data showed that
      the frequency depends on variables such as age and ethnicity.

PMID- 28756063
TI  - Alfaxalone alone or combined with midazolam or ketamine in dogs: intubation dose
      and select physiologic effects.
AB  - OBJECTIVE: To determine the intubation dose and select physiologic effects of
      alfaxalone alone or in combination with midazolam or ketamine in dogs. STUDY
      DESIGN: Prospective, clinical study. ANIMALS: Fifty-three healthy client-owned
      dogs [mean+/-standard deviation (SD)] 5.1+/-1.8 years, 27+/-15.4 kg, scheduled
      for elective orthopedic surgery. METHODS: After premedication with acepromazine
      (0.02 mg kg-1) and hydromorphone (0.1 mg kg-1) intramuscularly, alfaxalone (0.25
      mg kg-1) was administered intravenously over 15 seconds followed immediately by
      0.9% saline (AS), midazolam (0.3 mg kg-1; AM), ketamine (1 mg kg-1; AK1), or
      ketamine (2 mg kg-1; AK2). Additional alfaxalone (0.25 mg kg-1 increments) was
      administered as required to permit endotracheal intubation. The incidence of
      apnea and the time from intubation until spontaneous movement were recorded.
      Heart rate (HR) and blood pressure were recorded 15 minutes after premedication,
      after intubation and 2, 5, 10 and 15 minutes thereafter. Blood was collected for
      measurement of serum glucose and insulin concentrations before induction, after
      intubation and at 2, 5, 10 and 50 minutes. Data were analyzed by split-plot anova
      with Bonferroni adjustment for the number of group comparisons. RESULTS: Mean+/
      SD alfaxalone mg kg-1 doses required for endotracheal intubation were AS (1.0+/
      0.4), AM (0.4+/-0.2), AK1 (0.5+/-0.3) and AK2 (0.5+/-0.4) (p=0.0005). Differences
      in cardiopulmonary variables among groups were minor; HR decreased in AS, while
      in other groups, HR increased transiently postintubation. Incidence of apnea in
      AS was 54% with no significant difference among groups. Midazolam significantly
      prolonged time from intubation until spontaneous movement (p<0.002). CONCLUSIONS
      AND CLINICAL RELEVANCE: Midazolam and ketamine reduced the alfaxalone dose
      required for endotracheal intubation. Serum glucose and insulin concentrations
      were not influenced by administration of alfaxalone alone or when administered
      with midazolam or ketamine.

PMID- 28756064
TI  - CT- versus MRI-based patient-specific instrumentation for total knee
      arthroplasty: A systematic review and meta-analysis.
AB  - BACKGROUND: To determine whether computed tomography (CT) or magnetic resonance
      imaging (MRI) is more suitable for the patient-specific instrumentation (PSI)
      systems for total knee arthroplasty (TKA). METHODS: PubMed, Embase, and the
      Cochrane Library were searched from inception to June 2016 for prospective
      comparative trials that compared CT- versus MRI-based PSI systems for TKA. Our
      predefined primary outcome was the outliers incidence of coronal overall limb
      alignment. RESULTS: Six studies with a total of 336 knees meeting the eligibility
      criteria, and four trials were included in the meta-analysis. Compared with MRI
      based PSI systems, CT-based PSI systems were associated with a higher outliers
      incidence of coronal overall limb alignment (risk ratio: 1.67; 95% confidence
      interval (CI): 1.03-2.72; P = 0.04), more angular errors of coronal overall limb
      alignment (mean difference (MD): 1.01 degrees ; 95% CI: 0.47-1.56; P = 0.0003),
      and longer operation time (MD: 5.02 min; 95% CI: 1.26-8.79; P = 0.009). While no
      significant differences in the coronal/sagittal alignment of the femoral/tibial
      component outliers, the angular errors of coronal overall limb alignment, the
      angular errors of the femoral/tibial component in coronal plane, or incidence of
      change of implant size of the femoral/tibial component were observed.
      CONCLUSIONS: The current limited evidence suggests that MRI-based PSI systems
      exhibit higher accuracy for TKA regarding the coronal limb axis than CT-based PSI
      systems. However, well-designed studies comparing CT-versus MRI-based PSI systems
      for TKA are warrant to confirm these results before widespread use of this
      technique can be recommended.

PMID- 28756065
TI  - Relationship Between Atrasentan Concentrations and Urinary Albumin to Creatinine
      Ratio in Western and Japanese Patients With Diabetic Nephropathy.
AB  - PURPOSE: The objective of the current analyses was to characterize the
      pharmacokinetic properties of atrasentan and the exposure-response relationships
      for the efficacy end point, urinary albumin to creatinine ratio (UACR), and the
      treatment-emergent adverse event, peripheral edema, during 8 or 12 weeks of
      treatment. METHODS: Results from 3 Phase II, randomized, double-blind, placebo
      controlled studies (N = 257) were used for the population pharmacokinetic and
      exposure-response models. Concentration-time and response data for efficacy and
      tolerability were analyzed using a nonlinear mixed-effects population analysis
      and logistic regression approaches. FINDINGS: The pharmacokinetic data were
      adequately described by a 2-compartment model with first-order absorption and
      elimination. After weight was accounted for, no clinically meaningful differences
      were found in CL/F or Vd/F of the central compartment between Western and
      Japanese patients. Exposure-response analyses confirmed the efficacy of
      atrasentan in reducing UACR, with an estimated decrease in UACR of >=37% when the
      atrasentan dose was 0.75 mg or higher. No significant association between
      atrasentan exposure and the rate of edema was identified at atrasentan doses of
      0.5, 0.75, and 1.25 mg. The rates of peripheral edema were comparable in patients
      receiving active treatment and placebo. IMPLICATIONS: The exposure-response
      relationships for efficacy and tolerability were consistent between Western and
      Japanese patients. On the basis of these analyses, a dose of 0.75 mg/d was
      selected for the Phase III trial. ClinicalTrials.gov identifiers: NCT01356849,
      NCT01399580, and NCT01424319.

PMID- 28756067
TI  - Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in
      Healthy Postmenopausal Women.
AB  - PURPOSE: Bazedoxifene is a selective estrogen receptor modulator that has
      estrogen agonist effects on bone and lipid metabolism while having neutral or
      estrogen antagonist effects on the breast and endometrium. The present report
      describes findings from 3 Phase I clinical studies that evaluated the single-dose
      pharmacokinetics (study 1; n = 84), multiple-dose pharmacokinetics (study 2; n =
      23), and absolute bioavailability (study 3; n = 18) of bazedoxifene. METHODS: All
      3 studies enrolled healthy postmenopausal women who were either naturally
      postmenopausal or had undergone bilateral oophorectomy at least 6 months before
      the start of the study. FINDINGS: Study 1 showed that unconjugated and total
      (unconjugated and conjugated) bazedoxifene levels increased proportionally with
      ascending oral doses of bazedoxifene (through the dose range of 5-120 mg).
      Evaluation with or without food intake was conducted at the 10-mg dose, with no
      clinically relevant effect on pharmacokinetic parameters. Study 2 showed that
      bazedoxifene achieved steady state in 1 week and exhibited linear
      pharmacokinetics in doses of 5 to 40 mg with no unexpected accumulation over the
      dose range. In accordance with a linear pharmacokinetic profile, mean maximum
      plasma concentration values increased with increasing dose, with values of 1.6,
      6.2, and 12.5 ng/mL for the 5-, 20-, and 40-mg doses, respectively. In study 3,
      tablet and capsule formulations of bazedoxifene formulations had an estimated
      oral bioavailability of ~6%. The clearance of bazedoxifene was 0.4 (0.1) L/h/kg
      based on intravenous administration. The oral formulations had comparable
      exposure profiles with respect to AUC and AUC0-t, and the 90% CIs for these
      values were within the bioequivalence limits of 80% to 125%. Bazedoxifene was
      safe and well tolerated in all 3 studies. IMPLICATIONS: These pharmacokinetic
      evaluations in healthy postmenopausal women found that bazedoxifene displayed
      linear pharmacokinetics with doses ranging from 5 to 40 mg, with no unexpected
      accumulation. Food did not seem to have any clinically relevant impact on
      pharmacokinetic parameters. Bazedoxifene had an estimated oral bioavailability of
      ~6% and was safe and well tolerated in the range of doses evaluated.

PMID- 28756066
TI  - Prospects and Challenges in the Development of a Norovirus Vaccine.
AB  - PURPOSE: Norovirus is the leading cause of acute epidemic gastroenteritis among
      children under the age of 5 years and adults in the United States and in adults
      worldwide, accounting for an estimated 20% of episodes of acute gastroenteritis
      across all ages. No effective vaccine is presently available. This article
      provides an overview of the current state of norovirus vaccine development,
      emphasizing barriers and challenges in the development of an effective vaccine,
      correlates of protection used to assess vaccine efficacy, and the results of
      clinical trials of the major candidate vaccines. METHODS: We performed an
      unstructured literature review of published articles listed in PubMed in the
      field of norovirus vaccine development, with an emphasis on studies in humans.
      FINDINGS: Two candidate vaccines have reached clinical trials, and a number of
      other candidates are in the preclinical stages of development. Multivalent
      vaccination may be effective in inducing broadly neutralizing antibodies
      protective against challenge with novel and heterologous norovirus strains. Most
      identified correlates of protection have not been validated in large-scale
      challenge studies, nor have the degrees to which these correlates covary been
      assessed. IMPLICATIONS: Immune correlates of protection against norovirus
      infection need to be further developed to facilitate additional studies of the
      tolerability and efficacy of candidate norovirus vaccines in humans.

PMID- 28756068
TI  - A Phase II Randomized, Double-blind, Multicenter Study to Evaluate Efficacy and
      Safety of Intravenous Iclaprim Versus Vancomycin for the Treatment of Nosocomial
      Pneumonia Suspected or Confirmed to be Due to Gram-positive Pathogens.
AB  - PURPOSE: The primary objective of this Phase II study was to compare the clinical
      cure rates of 2 iclaprim dosages versus vancomycin in the treatment of patients
      with nosocomial pneumonia suspected or confirmed to be caused by gram-positive
      pathogens. METHODS: This study was a double-blind, randomized, multicenter trial.
      A total of 70 patients were randomized 1:1:1 to receive iclaprim 0.8 mg/kg IV
      q12h (iclaprim q12h; n = 23), iclaprim 1.2 mg/kg IV q8h (iclaprim q8h; n = 24),
      or vancomycin 1 g IV q12h (vancomycin; n = 23) for 7 to 14 days. The primary end
      point was clinical cure in the intention-to-treat population at test of cure
      (TOC; 7 [1] days' posttreatment) visit. FINDINGS: The baseline and demographic
      characteristics of patients treated with either iclaprim or vancomycin were
      comparable. Cure rates in the intention-to-treat population were 73.9% (17 of
      23), 62.5% (15 of 24), and 52.2% (12 of 23) at the TOC visit in the iclaprim
      q12h, iclaprim q8h, and vancomycin groups, respectively (iclaprim q12h vs
      vancomycin, P = 0.13; iclaprim q8h vs vancomycin, P = 0.47). The death rates
      within 28 days of the start of treatment were 8.7% (2 of 23), 12.5% (3 of 24),
      and 21.7% (5 of 23) for the iclaprim q12h, iclaprim q8h, and vancomycin groups
      (no statistically significant differences). The adverse event profile of both
      iclaprim dosing regimens was similar to that of vancomycin. IMPLICATIONS:
      Iclaprim had clinical cure rates and a safety profile comparable with vancomycin
      among patients with nosocomial pneumonia. Iclaprim could be an important new
      therapeutic option for the treatment of nosocomial pneumonia, and a pivotal
      clinical trial is warranted to evaluate its safety and efficacy in this
      indication.

PMID- 28756069
TI  - Gliosarcoma in septuagenarians and octogenarians: What is the impact of adjuvant
      chemoradiation?
AB  - The objective of our study is to determine the impact of adjuvant chemoradiation
      on overall survival (OS) for gliosarcoma in septuagenarians and octogenarians.
      Data were extracted from the National Cancer Data Base (NCDB). Chi-square test,
      Kaplan-Meier method, and Cox regression models were employed in SPSS 23.0
      (Armonk, NY: IBM Corp.) for data analyses. 210 patients with gliosarcoma who
      underwent resection were identified. 168 (80.0%) patients received adjuvant
      chemoradiation, and 42 (20.0%) received adjuvant RT alone. Patients were more
      likely to receive adjuvant chemoradiation if they were male vs. female (85.3% vs.
      71.6%, p=0.016). There was no significant difference in receipt of adjuvant
      therapy by year of diagnosis, age at diagnosis, race, Charlson/Deyo Score,
      treatment facility type, tumor size, or extent of surgery. Those who received
      adjuvant chemoradiation had significantly better one-year OS than those who
      received adjuvant radiation alone (35.3% vs. 16.2%, p<0.001). On subset analysis,
      this significant one-year OS benefit was observed in septuagenarians, those with
      Charlson/Deyo Score of 0, and in those with tumor size <=5cm. On multivariate
      analysis, receipt of adjuvant chemoradiation and greater extent of resection were
      independent prognostic factors for improved OS. Our data suggests that adjuvant
      chemoradiation is an independent prognostic factor for improved OS in elderly
      patients with gliosarcoma, and the results of our study can serve as estimated
      benchmarks for outcome in this growing and important patient population. Its
      benefit, however, may be limited to septuagenarians and those with lower
      comorbidity burden.

PMID- 28756070
TI  - Diagnostic and prognostic value of cystatin C in acute heart failure.
AB  - BACKGROUND: The accurate early diagnosis of acute kidney injury (AKI) in patients
      with acute heart failure (AHF) is an unmet clinical need. Cystatin C might
      improve the early detection of AKI. METHODS: 207 patients presenting to the
      emergency department with AHF were enrolled. Cystatin C was measured in plasma in
      a blinded fashion at presentation and serially thereafter. The potential of
      Cystatin C levels to predict AKI was assessed as the primary endpoint. Long-term
      mortality was assessed as a secondary endpoint. RESULTS: At presentation,
      creatinine (140MUmol/L [91-203] vs. 97MUmol/L [76-132], p<0.01) and Cystatin C
      (2.00mg/L [1.30-3.08] vs. 1.45mg/L [1.00-1.90], p<0.01) levels were significantly
      higher in AKI compared to Non-AKI patients. The diagnostic accuracy for AKI
      quantified by the area under the receiver operating characteristic curve was
      mediocre and comparable for both markers (creatinine 0.68; 95%CI 0.58-78 vs.
      Cystatin C 0.67; 95%CI 0.58-0.76). Serial measurements of Cystatin C did not
      further increase the prognostic accuracy for AKI. Cystatin C levels were
      significantly higher in decedents than in survivors (1.90mg/L [1.30-2.70] vs.
      1.30mg/L [1.0-1.6], p<0.001). The combination of Cystatin C and BNP levels
      significantly improved the prediction of mortality provided by either parameter
      alone. In multivariable regression analysis Cystatin C remained independently
      associated with mortality (HR 1.41; 95%CI 1.02-1.95). CONCLUSION: Plasma Cystatin
      C levels do not adequately predict AKI in patients with AHF. However, in
      multivariable regression analysis Cystatin C predicted mortality after the
      adjustment for baseline renal function, AKI, BNP levels and heart failure risk
      factors.

PMID- 28756071
TI  - [How to detect myocardial ischemia in patients following acute coronary syndrome
      treated by PCI?]
AB  - Unstable coronary artery disease is a more aggressive condition than stable
      coronary artery disease, accounting for the high incidence of major adverse
      cardiovascular events following acute coronary syndromes (ACS), which includes
      the need for iterative repeat revascularization. The aim of myocardial ischemia
      screening in post-ACS patients is to detect this unfavourable evolution (either
      on initial culprit or non culprit lesions) and to prevent any clinical
      complication. Although there is no strict recommendation in this particular
      situation, screening should be based on the use of stress imaging techniques. The
      optimal timing and frequency for testing will depend on the clinical
      characteristics of the patients and the coronary revascularization procedure
      features.

PMID- 28756072
TI  - Epidemiology of Takayasu arteritis.
AB  - Takayasu arteritis (TA), a granulomatous large vessel vasculitis involves mostly
      the aorta and its proximal branches and occurs most commonly in young females.
      The data on the epidemiology of TA is limited, probably due to the rarity of the
      disease. Although the disease has a worldwide distribution, it is generally
      thought to be much more common among Asian populations. The incidences of TA were
      estimated to be 1-2 per million in Japan and 2.2 per million in Kuwait. Recent
      epidemiologic studies suggest that TA is being increasingly recognized in Europe
      with reported incidence estimates varying from 0.4 to 1.5 per million. The
      highest ever prevalence of TA at 40 per million was estimated in Japan and the
      lowest ever one at 0.9 per million in US. The reported prevalences in the
      European populations vary between the ranges of 4.7 per million and 33 per
      million. These variations between the studies may be derived from geographical
      and genetic differences between the populations, but also may be due to the
      methodological differences.

PMID- 28756074
TI  - [European Guidelines on cardiac arrest, what's new?]
AB  - The European recommendations on cardiac arrest are based on the evidence gathered
      and reviewed by the International Resuscitation Liaison Committee (ILCOR) and
      were published in October 2015. These recommendations without representing a
      revolution, constitute an evolution centered on a primary goal to increase
      survival following cardiac arrest. This improvement in survival depends on four
      main factors: early identification of cardiac arrest, early access to rescue,
      early and quality CPR, and access to early defibrillation. These recommendations
      underline the importance of the interactions between the actors involved in the
      management of cardiac arrest: medical emergency dispatching personnel, the first
      provider who administers the CPR and the actors responsible for the deployment of
      public access defibrillation.

PMID- 28756073
TI  - The genetics of Takayasu arteritis.
AB  - Takayasu arteritis (TAK) is a rare systemic vasculitis that is characterized by
      granulomatous inflammation of the aorta and its major branches. The cellular and
      biochemical processes involved in the pathogenesis of TAK are beginning to be
      elucidated, and implicate both cell and antibody-mediated autoimmune mechanisms.
      In addition, the underlying etiology to TAK may be explained, at least in part,
      by a complex genetic contribution. The most well-recognized genetic
      susceptibility locus for the disease is the classical HLA allele, HLA-B*52, which
      has been confirmed in several ethnicities. The genetic susceptibility with HLA
      B*52, as well as additional classical alleles and loci, implicate both HLA class
      I and class II involvement in TAK. Furthermore, genetic associations with genes
      encoding immune response regulators, pro-inflammatory cytokines and mediators of
      humoral immunity may directly relate to disease mechanisms. Non-HLA
      susceptibility loci that have been recently established for TAK with a genome
      wide level of significance include FCGR2A/FCGR3A, IL12B, IL6, RPS9/LILRB3, and a
      locus on chromosome 21 near PSMG1. In this review, we present the complex genetic
      predisposition to TAK and discuss how recent findings identified potential
      targets in the pathogenesis and treatment of the disease.

PMID- 28756075
TI  - [TAVI: History and perspectives].
AB  - Nearly 20 years have passed from the concept to clinical development of
      percutaneous aortic valve replacement, starting from an idea considered "stupid"
      of Professor Alain Cribier in Rouen. After a first phase of compassionate
      implantation, large randomized trials PARTNER and COREVALVE US have allowed TAVI
      to impose itself in the European and American recommendations in patients
      inoperable or considered with high surgical risk. Next European recommendations
      on the management of valvular heart diseases expected in 2017 should take into
      account the positive results observed in intermediate risk patients in the
      PARTNER 2 and SURTAVI studies, recently adopted in the US recommendations.
      Randomized trials in "all coming" patients are already on their way, and the
      future of TAVI is to be the reference treatment for a vast majority of patients
      with aortic stenosis.

PMID- 28756076
TI  - [Anticoagulation after an acute pulmonary embolism].
AB  - In order to determine the optimal duration of anticoagulation after an acute
      pulmonary embolism, the benefit risk balance needs to be analysed based on the
      risk of recurrent venous thromboembolism in the absence of anticoagulation and
      the risk of bleeding while on anticoagulant therapy. Such evaluation take in
      account the frequency and the severity of the risks; clinical variables appear
      more informative to predict recurrent venous thromboembolism than biochemical or
      morphological variables. Three major results are now available: (1) the minimal
      duration of anticoagulation for pulmonary embolism is 3 months; (2) after
      pulmonary embolism that was provoked by a major transient risk factor, the risk
      of recurrence is low and does not justify to prolong anticoagulation beyond 6
      months; and (3), in patients with an unprovoked pulmonary embolism (high risk of
      recurrence), the prolongation of anticoagulation up to 1 or 2 years as compared
      to 3 or 6 months is not associated with a long term reduction in the risk of
      recurrence and, consequently, these patients should be treated either during 3 to
      6 months or indefinitely. This last observation has two major implications:
      first, to identify, among patients with unprovoked pulmonary embolism, those who
      have a low risk of recurrence and who do not require indefinite anticoagulation;
      and second, in those who are eligible for indefinite anticoagulation, to reduce
      the risk of bleeding. If direct oral anticoagulant therapies are promising,
      however, additional clinical trials are needed to help physician for the daily
      practice.

PMID- 28756077
TI  - [The gut microbiota, a new cardiovascular risk factor?]
AB  - The gut microbiota is considered as our other "brain" and is implicated in
      several regulation of physiological metabolisms. The circulating level of TMAO, a
      metabolite of the gut microbiota, is directly correlated to the occurrence of
      cardiovascular events. Bile acids are protective metabolites against
      cardiovascular diseases through their anti-inflammatory and anti-atherogenic
      effects. The disturbance in the metabolism and the composition of the gut
      microbiota is called "dysbiosis". Understanding the implication of the gut
      microbiota and developing new therapeutic strategies are promising research
      fields to manage metabolic and cardiovascular diseases.

PMID- 28756078
TI  - Patient-reported outcomes in Takayasu's arteritis.
AB  - Patient-reported outcomes (PROs) are assessment tools coming directly from
      patients about their feelings, perceptions, health-related functions, and
      treatment effects without interpretation by health-care providers. There is a
      global interest for more "patient-centered care" and PROs in rheumatology.
      Assessment of disease impact through patient-reported outcome (PRO) measures is a
      key element for clinical care and clinical research in Takayasu's arteritis
      (TAK). Currently there are no disease-specific PRO measures to assess quality of
      life for patients with TAK. Impaired health-related quality of life (HRQoL),
      functional status, increased anxiety, and depression were shown in patients with
      TAK in a few studies with generic PRO instruments such as the Short Form-36.
      However, it is difficult to capture disease-specific effects on patients' daily
      life and quality of life with these generic tools. There are ongoing efforts of
      Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group to develop
      disease-specific outcome measures in TAK.

PMID- 28756079
TI  - [Exercise testing: New guidelines].
AB  - The GERS (Exercise Rehabilitation and Sports Group of the French Society of
      Cardiology) has decided to update current guidelines regarding the practice of
      EKG stress tests. Since the last update dates from 1997, the GERS judged it
      necessary to integrate data from new works and advancements made in the last 20
      years. Good clinical practices and safety conditions are better defined regarding
      the structure, location, material, staff competency, as well as convention with
      hospital structures. The diagnosis of coronary artery disease remains the
      principal indication for a stress test. Interpretation of the results is crucial
      it must be multivariate and provide either a low, intermediate or strong
      probability of the existence of coronary lesions, taking into account the studied
      population (risk factors, age, sex and symptoms). Several new indications for a
      stress test have been defined for the assessment of cardiac pathologies. With
      such indications, the use of gas expiration measurements is highly recommended in
      order to provide a precise prognosis for all the various cardiac pathologies :
      congenital, ischemic, valvular, cardiomyopathies, congestive heart failure,
      rhythm and conduction disorders, pacemaker fine-tuning, or pulmonary
      hypertension. Indications for stress tests and contraindications are defined
      according to different population subgroups, for instance : athletes, women,
      children, the elderly, asymptomatic patients, diabetics, hypertensive patients,
      PAD patients, or in the context of a non-cardiac surgery pre-op visit. The new
      guidelines (due for publication soon) are considerably different from those
      dating from 1997 and further pinpoint the relevance and importance of an EKG
      stress test within the arsenal of complementary cardiologic exams. With the
      improvements made in providing diagnostic value in CAD, as well as better
      prognostic value for any underlying pathology, the indication for an EKG stress
      test has extended to all cardiovascular disease.

PMID- 28756080
TI  - [How to prescribe sport in patients?]
AB  - Physical activity is a non-pharmacological treatment validated by the Haute
      Autorite de sante since 2011. Since March 2017, a new French law recalls that
      generalist physicians can prescribe physical activity to their patients suffering
      from a long-term financial exonerating condition. This physical activity will be
      adapted to the individual physical capacities and medical risk of the patient.
      After assessing his/her functional abilities, the attending physician will send
      the patient, with his or her agreement, to a supervisory structure employing
      specifically trained professional for physical activity. It should be noted that
      neither the prescription nor the dispensation of adapted physical activity are
      covered by health insurance. The introduction of training in the prescription of
      physical activity in the framework of medical studies will be indispensable for
      the success of this law.

PMID- 28756081
TI  - Temporal Trends in Epinephrine Dispensing and Allergy/Immunology Follow-up Among
      Emergency Department Anaphylaxis Patients in the United States, 2005-2014.
AB  - BACKGROUND: Anaphylaxis is a potentially life-threatening allergic reaction;
      measures including prescription of an epinephrine autoinjector (EAI) and
      allergy/immunology (A/I) follow-up may prevent future morbidity. OBJECTIVE: The
      objective of this study was to evaluate trends in outpatient management of
      anaphylaxis by studying EAI dispensing and A/I follow-up among patients seen in
      the emergency department (ED) for anaphylaxis from 2005 through 2014. METHODS: We
      analyzed administrative claims data from the OptumLabs Data Warehouse database
      using an expanded International Classification of Diseases, Ninth Revision,
      Clinical Modification diagnosis code algorithm. RESULTS: The study cohort
      comprised 18,279 patients with a mean age of 39 years; 58% were female, and 86%
      were discharged from an ED. Within 1 year after discharge, 46% had filled an EAI
      prescription and 29% had A/I follow-up. Overall, from 2005 to 2014, annual rates
      of filled EAI prescriptions and A/I follow-up did not change. Among children
      (aged <18 years), rates increased for filled EAI prescriptions (16.1% increase; P
      = .02 for trend) and A/I follow-up (18.8% increase; P = .048 for trend). Rates
      decreased for A/I follow-up among adults (15.4% decrease; P = .002 for trend).
      Overall rates of filled EAI prescriptions were highest in those with venom
      induced (73.9 per 100 ED visits) and food-induced anaphylaxis (69.4 per 100 ED
      visits); the lowest rates were among those with medication-related anaphylaxis
      (18.2 per 100 ED visits). CONCLUSIONS: Over the past decade, rates of EAI
      dispensing and A/I follow-up after an ED visit for anaphylaxis have remained low,
      suggesting that patients may not be prepared to manage future episodes.

PMID- 28756083
TI  - Editorial overview: Molecular imaging for seeing chemistry in biology.

PMID- 28756082
TI  - Asthma Morbidity, Comorbidities, and Modifiable Factors Among Older Adults.
AB  - BACKGROUND: Asthma morbidity is increased among older adults, especially older
      adult women. Interventions to improve asthma control in this population are not
      well described. OBJECTIVE: The objective of this study was to identify risk
      factors (including modifiable factors) associated with asthma-related
      hospitalizations and emergency department or urgent care center visits (ED/UCV)
      among older adults. A secondary objective was to investigate sex differences in
      variables relevant to asthma control. METHODS: Data were obtained from 14,076
      older adults >=65 years with active asthma participating in the 2006-2010
      Behavioral Risk Factor Surveillance System Asthma Call-back Survey (a random
      digit dialed survey) in 40 US states, the District of Columbia, and Puerto Rico,
      representative of >2.6 million persons. Weighted, adjusted logistic regression
      was conducted. RESULTS: One or more asthma-related hospitalizations in the past
      year were reported by 5.7% (95% confidence interval [95% CI] = 5.0% to 6.4%) of
      participants; 10.6% (95% CI = 9.7% to 11.5%) reported >=1 asthma-related ED/UCV.
      Compared with older adults without asthma-related hospitalizations, adjusted odds
      were higher among those with >=1 asthma-related hospitalization for chronic
      obstructive pulmonary disease (COPD), coronary artery disease, depression,
      cockroaches or mold in the home, and cost barriers to asthma-related health care
      or medication. All these factors, except for cockroaches, were associated with
      asthma-related ED/UCV. Compared with males, adjusted odds were higher among
      females for COPD, depression, obesity, and cost barriers to asthma-related health
      care or medication. CONCLUSIONS: Among older adults, asthma-related
      hospitalizations and ED/UCV were associated with clinical comorbidities, mold in
      the home, and financial barriers to asthma-related health care. Interventions
      addressing modifiable factors could reduce asthma morbidity among older adults.

PMID- 28756084
TI  - Emerging therapies for multiple myeloma: Application in older adults.
AB  - Tremendous advances in the treatment of multiple myeloma have yielded
      improvements in survival in patients with multiple myeloma. A number of pivotal
      phase III trials have established the benefit of these newer agents in
      individuals with relapsed multiple myeloma. Because older adults are under
      enrolled in clinical trials, clinical trial data may not be categorically
      generalizable to more vulnerable older adults. In this review, the applicability
      to older adults of recent clinical trials of newer agents in older adults with
      myeloma are examined, with attention to eligibility criteria, dosing of therapy,
      characteristics of the population, and subgroup analyses of older adults.

PMID- 28756085
TI  - Differentiation of Intrahepatic Cholangiocellular Carcinoma from Hepatocellular
      Carcinoma in the Cirrhotic Liver Using Contrast-enhanced MR Imaging.
AB  - RATIONALE AND OBJECTIVES: This study aimed to investigate the potential of
      contrast-enhanced magnetic resonance imaging features to differentiate between
      mass-forming intrahepatic cholangiocellular carcinoma (ICC) and hepatocellular
      carcinoma (HCC) in cirrhotic livers. MATERIALS AND METHODS: This study, performed
      between 2001 and 2013, included 64 baseline magnetic resonance imaging
      examinations with pathohistologically proven liver cirrhosis, presenting with
      either ICC (n = 32) or HCC (n = 32) tumors. To distinguish ICC form HCC tumors,
      20 qualitative single-lesion descriptors were evaluated by two readers, in
      consensus, and statistically classified using the chi-square automatic
      interaction detection (CHAID) methodology. Diagnostic performance was assessed by
      a receiver operating characteristic analysis. RESULTS: The CHAID algorithm
      identified three independent categorical lesion descriptors, including (1) liver
      capsular retraction; (2) progressive or persistent enhancement pattern or wash
      out on the T1-weighted delayed phase; and (3) signal intensity appearance on T2
      weighted images that could help to reliably differentiate ICC from HCC, which
      resulted in an AUC of 0.807, and a sensitivity and specificity of 68.8 and 90.6
      (95% confidence interval 75.0-98.0), respectively. CONCLUSIONS: The proposed
      CHAID algorithm provides a simple and robust step-by-step classification tool for
      a reliable and solid differentiation between ICC and HCC tumors in cirrhotic
      livers.

PMID- 28756086
TI  - Iterative beam-hardening correction with advanced modeled iterative
      reconstruction in low voltage CT coronary calcium scoring with tin filtration:
      Impact on coronary artery calcium quantification and image quality.
AB  - OBJECTIVE: We investigated the impact of iterative beam-hardening correction
      (IBHC) with advanced modeled iterative reconstruction (ADMIRE) of ultra-low
      radiation-dose tin filtered (Sn100 kVp) CACS acquisitions on image quality,
      calcium quantification, and risk classification. METHODS: CT data of 60 patients
      (55% male, age 62.3 +/- 9.8years) who underwent a 3rd generation dual-source CACS
      scan using a prospectively ECG-triggered 100 kVp sequential acquisition protocol
      with tin filtration (Sn100 kVp) were reconstructed using IBHC with filtered back
      projection (FBP) and ADMIRE with strength levels of three and five. Image noise
      was calculated and Agatston scores were derived from all reconstructions. Image
      noise, Agatston score categories, and percentile-based cardiac risk
      categorization of the respective reconstruction techniques were compared.
      RESULTS: The mean estimated radiation dose equivalent of CACS acquisitions in the
      study population was 0.20 +/- 0.07 mSv. Mean image noise significantly decreased
      with ADMIRE compared to FBP (both p < 0.0001). Agatston scores derived from the
      respective reconstructions were significantly different in a paired comparison
      (median [25th and 75th percentile]): FBP 34.7 [1.9, 153.6], ADMIRE 3 28.6 [1.1,
      134.5], ADMIRE 5 22.7 [0.3, 116.8]; both p < 0.0001). Agatston score categories
      and cardiac risk categorization showed excellent agreement of ADMIRE 3 and ADMIRE
      5 with FBP (K = 0.92 [0.86-0.98] and K = 0.86 [0.79-0.94]; K = 0.94 [0.87-1.00]
      and K = 0.91 [0.83-0.99]; however, modest cardiac risk reclassifications of 3%
      and 7% for ADMIRE 3 and ADMIRE 5, respectively, were observed. CONCLUSION:
      Iterative reconstruction using IBHC ADMIRE in low voltage, ultra-low dose CACS
      with tin filtration significantly decreased image noise. However, it also reduced
      Agatston scores compared to FBP, which may have an impact on subsequent cardiac
      risk classification, although risk reclassification occurred only in a modest
      number of subjects.

PMID- 28756087
TI  - A Glimpse of Membrane Transport through Structures-Advances in the Structural
      Biology of the GLUT Glucose Transporters.
AB  - The cellular uptake of glucose is an essential physiological process, and
      movement of glucose across biological membranes requires specialized
      transporters. The major facilitator superfamily glucose transporters GLUTs,
      encoded by the SLC2A genes, have been a paradigm for functional, mechanistic, and
      structural understanding of solute transport in the past century. This review
      starts with a glimpse into the structural biology of membrane proteins and
      particularly membrane transport proteins, enumerating the landmark structures in
      the past 25years. The recent breakthrough in the structural elucidation of GLUTs
      is then elaborated following a brief overview of the research history of these
      archetypal transporters, their functional specificity, and physiological and
      pathophysiological significances. Structures of GLUT1, GLUT3, and GLUT5 in
      distinct transport and/or ligand-binding states reveal detailed mechanisms of the
      alternating access transport cycle and substrate recognition, and thus illuminate
      a path by which structure-based drug design may be applied to help discover novel
      therapeutics against several debilitating human diseases associated with GLUT
      malfunction and/or misregulation.

PMID- 28756088
TI  - Protein S100B in umbilical cord blood as a potential biomarker of hypoxic
      ischemic encephalopathy in asphyxiated newborns.
AB  - BACKGROUND: Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating
      condition resulting from a sustained lack of oxygen during birth. The interest in
      identifying a relevant biomarker of HIE has thrown into limelight the role of
      protein S100B as a clinical diagnostic marker of hypoxic brain damage in
      neonates. AIMS: To evaluate the diagnostic value of protein S100B, measured in
      umbilical cord blood immediately after birth, as a useful biomarker in the
      diagnosis of HIE Sarnat stages II-III as well as a marker for long-term mortality
      and morbidity. STUDY DESIGN: Protein S100B was analyzed in cord blood sampled at
      birth from 13 newborns later diagnosed with stage II-III HIE and compared with 21
      healthy controls. S100B concentrations were related to cord artery pH, amplitude
      integrated electroencephalography (aEEG), stage of HIE, and death/sequelae up to
      an age of 6years. Both parametric and non-parametric statistics were used with a
      two-sided P<0.05 considered significant. RESULTS: The difference in S100B
      concentration was marginally statistically significant between HIE cases and
      controls (P=0.056). Cord blood acidosis (P=0.046), aEEG pattern severity
      (P=0.030), HIE severity (P=0.027), and condition at 6-year follow-up
      (healthy/permanent sequelae/death; P=0.027) were all related to an increase in
      S100B concentration. CONCLUSIONS: Protein S100B in neonates suffering from HIE
      stages II-III appeared elevated in umbilical cord blood at birth. The S100B
      concentrations were positively associated to the severity of disease and the risk
      of suffering from neurodevelopmental sequelae and even death.

PMID- 28756089
TI  - Single particle extinction and scattering optical method unveils in real time the
      influence of the blood components on polymeric nanoparticles.
AB  - Here we report the quantitative in situ characterization of size distribution
      evolution of polymeric nanoparticles incubated in murine serum, filtered and
      unfiltered murine blood. We used an analytical optical approach, named Single
      Particle Extinction and Scattering (SPES), which relies on the measurements of
      two independent parameters of single particles. SPES is based on a robust self
      reference interference optical scheme which allows a rejection of the spurious
      signals coming from the background caused by the medium. We employed polystyrene
      nanoparticles as reference system and polydisperse poly(lactic-co-glycolic acid)
      nanoparticles. Our results demonstrate that SPES can be used for carrying out ex
      vivo analysis of nanoparticles to evaluate the modifications that NPs undergo in
      vivo following different routes of entry. Conversely, Dynamic Light Scattering is
      not able to provide reliable results for these systems due to the presence of the
      biological components in solution.

PMID- 28756090
TI  - Single oral dose of cannabinoid derivate loaded PLGA nanocarriers relieves
      neuropathic pain for eleven days.
AB  - Neuropathic pain, resistant to opiates and other drugs, is a chronic/persistent
      state with a complex treatment and often poor efficacy. In this scenario,
      cannabinoids are increasingly regarded as a genuine alternative. In this paper,
      and in an experimental animal model of neuropathic pain, we studied the efficacy
      of three kinds of PLGA nanoparticles containing synthetic cannabinoid CB13: (i)
      plain nanoparticles (PLGA); (ii) particles coated with PEG chains (PLGA+PEG) and
      (iii) particles possessing hydrophilic surfaces obtained by covalently binding
      PEG chains (PLGA-PEG). The optimized formulation, CB13-PLGA-PEG, showed high drug
      loading (13%) and small size (<300nm) with a narrow distribution and controlled
      surface properties (near-neutral zeta potential and stable PEG corona). Animal
      nociceptive behavioral studies were conducted by paw pressure and acetone tests.
      Versus the free CB13, CB13-PLGA-PEG nanoparticles showed a very noticeable
      analgesic efficacy with the longest sustained pain-relieving effect, lasting up
      to eleven days after one oral dose.

PMID- 28756091
TI  - Effect of silver nanoparticles upon the myocardial and coronary vascular function
      in isolated and perfused diabetic rat hearts.
AB  - Silver nanoparticles (AgNPs) are promising antibacterial nanomaterials for
      diagnostic and treatment of diabetes. However, toxicity and adverse cardiac
      responses induced by AgNPs related to nitric oxide (NO) and oxidative stress (OS)
      are described. Moreover, little is known about the diabetes influence upon AgNPs
      toxicity. The aim of this work was to evaluate cardiovascular function in
      response to AgNPs through measuring perfusion pressure (PP) and left ventricle
      pressure (LVP), using perfused hearts from streptozotocin (STZ)-induced diabetic
      rats and identify the role of NO and OS. High concentrations but not the lower
      concentrations of AgNPs, promotes increases in PP and LVP, as well as increased
      OS. Additionally, diabetes alters the classic effects of phenylephrine (Phe) and
      acetylcholine (ACh). These data suggest that diabetes may intensify AgNPs
      cardiotoxicity. Nevertheless, the precise mechanism of action is still under
      elucidation.

PMID- 28756092
TI  - Membrane wound healing at single cellular level.
AB  - We report a nano-technological method of creating a micrometer sized hole on the
      live cell membrane using atomic force microscope (AFM) and its resealing process
      at the single cellular level as a model of molecular level wound healing. First,
      the cell membrane was fluorescently labeled with Kusabira Orange (KO) which was
      tagged to a lipophilic membrane-sorting peptide. Then a glass bead glued on an
      AFM cantilever and modified with phospholipase A2 was made to contact the cell
      membrane. A small dark hole (4-14 MUm2 in area) was created on the otherwise
      fluorescent cell surface often being accompanied by bleb formation. Refilling of
      holes with KO fluorescence proceeded at an average rate of ~0.014MUm2s-1. The
      fluorescent lumps which initially surrounded the hole were gradually lost. We
      compared the present result with our previous ones on the repair processes of
      artificially damaged stress fibers (Graphical Abstract: Figure S2).

PMID- 28756093
TI  - Noninvasive nanoparticle strategies for brain tumor targeting.
AB  - The blood-brain barrier (BBB) maintains the integrity and homeostasis of the
      central nervous system (CNS) yet represents an intimidating hurdle for efficient
      drug delivery to brain tumors. This up-to-date review summarizes strategies that
      have been employed to cross the BBB with a focus on non-invasive nanoparticles
      that could pass the BBB after systemic administration. Recent advances in
      liposomes, polymeric nanoparticles, micelles, and inorganic nanoparticles are
      scrutinized mechanistically with an emphasis on design principles. As highlighted
      in this review, effective drug delivery to brain tumors may be achieved by
      rationally engineering nanoparticles to possess appropriate sizes, surface
      properties, and ligands.

PMID- 28756094
TI  - Nanotraps with biomimetic surface as decoys for chemokines.
AB  - A creation of nanotraps that could selectively recognize the chemotactic
      mediators of leukocyte adhesion and eliminate them from the bloodstream and
      tissue intercellular matrix is a promising approach for the treatment of various
      inflammatory and autoimmune diseases. We designed nanotraps as artificial decoy
      receptors based on poly(lactic acid) (PLA) nanoparticles covered by heparin and
      bearing on the surface two fragments of CCR5 receptor (N-terminal domain, Nt, and
      second extracellular loop, ECL2), responsible for chemokine binding. In order to
      attach Nt and ECL2 to the heparin shell, the corresponding peptides were modified
      with N- and/or C-terminal oligolysines. The presence of the nanotraps in the cell
      medium completely eliminated the activating effect of a CCR5 ligand, chemokine
      Rantes, while strongly decreasing the adhesion of monocytes to the human
      endothelial cells. We found that the modified ECL2 alone was also able to prevent
      monocyte adhesion, thus acting as a decoy receptor itself.

PMID- 28756095
TI  - Surgical considerations and safety of cochlear implantation in otitis media with
      effusion.
AB  - OBJECTIVE: To evaluate the effects of otitis media with effusion on surgical
      parameters, patient safety, perioperative and postoperative complications.
      METHODS: Total 890 children who underwent cochlear implantation between 2006 and
      2015 were included. The ages ranged from 12 months to 63 months (mean: 32
      months). The patients were divided into two groups according to the presence or
      absence of otitis media with effusion; otitis media with effusion group and non
      otitis media group. RESULTS: Of 890 children, 105 had otitis media with effusion
      prior to surgery. In non-otitis media with group, there were 785 children. The
      average duration of surgery was 60min (ranged from 28 to 75min) in non-otitis
      media group, and 90min (ranged from 50 to 135min) in otitis media with effusion
      group (p<0.05). Granulation tissue and edematous middle ear and mastoid mucosa
      were observed in all cases of otitis media with effusion during the surgery.
      There was no significant difference between the complications of groups with or
      without otitis media with effusion (p>0.05). In 5 of 105 patients, there was a
      ventilation tube inserted before cochlear implantation, which did not change the
      outcome of implantation. CONCLUSION: There is no need for surgical treatment for
      otitis media with effusion before implantation since otitis media with effusion
      does not increase the risks associated with cochlear implantation. Operation
      duration is longer in the presence of otitis media with effusion. However, otitis
      media with effusion leads to intraoperative difficulties like longer operation
      duration, bleeding, visualization of the round window membrane, cleansing the
      middle ear granulations as well as mastoid and petrous air cells.

PMID- 28756096
TI  - Endoscopic contralateral transmaxillary approach for pterygoid process osteotomy
      in total maxillectomy: A technical case report.
AB  - An approach for total maxillectomy with endoscopic transection of the pterygoid
      process via the contralateral maxillary sinus is described. In total
      maxillectomy, the resection of the pterygoid process of the sphenoid is a key
      step for successful resection. However, a conventional craniofacial approach
      requires extensive incision in the face, elevation of the lateral cheek flap.
      Even after elevation of the lateral cheek flap, visualization of this region is
      not good. An endoscopic approach through the contralateral maxillary sinus
      improved visualization of the pterygoid process, and osteotomy using a diamond
      drilling bar was successfully performed. This technique has the potential to
      widen the indication for total maxillectomy in malignant neoplasms of the
      maxillary sinus.

PMID- 28756097
TI  - Impact of the Korean Diagnosis-Related Groups payment system on the outcomes of
      adenotonsillectomy: A single center experience.
AB  - OBJECTIVES: To report outcomes with regard to clinical aspects and medical costs
      of adenotonsillectomy and tonsillectomy at a single institution before and after
      implementation of the Diagnosis-Related Groups (DRG) payment system in Korea.
      METHODS: We retrospectively reviewed the records of patients treated with
      adenotonsillectomy or tonsillectomy between July 2012 and June 2014. The Korean
      DRG payment system was applied to seven groups of specific diseases and surgeries
      including adenotonsillectomy and tonsillectomy from July 2013 at all hospitals in
      Korea. We divided patients into four groups according whether the fee-for-service
      (FFS) or DRG payment system was implemented and operation type (FFS
      adenotonsillectomy (AT), DRG-AT, FFS-tonsillectomy (T), and DRG-T). RESULTS: A
      total of 1402 patients were included (485 FFS-AT, 490 DRG-AT, 203 FFS-T, and 223
      DRG-T). The total medical cost of the DRG-AT group was significantly lower than
      that of the FFS-AT group (1191+/-404 vs. 1110+/-279 USD, P<0.05). There were no
      significant differences in length of hospital stay or postoperative complications
      among groups. CONCLUSION: The Korean DRG system for adenotonsillectomy and
      tonsillectomy reduced medical costs and clinical outcomes were not significantly
      altered by the adoption of the DRG system. LEVEL OF EVIDENCE: 4.

PMID- 28756098
TI  - Phenotypic variability in LQT3 human induced pluripotent stem cell-derived
      cardiomyocytes and their response to antiarrhythmic pharmacologic therapy: An in
      silico approach.
AB  - BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC
      CMs) are in vitro models with the clear advantages of their human origin and
      suitability for human disease investigations. However, limitations include their
      incomplete characterization and variability reported in different cell lines and
      laboratories. OBJECTIVE: The purpose of this study was to investigate in silico
      ionic mechanisms potentially explaining the phenotypic variability of hiPSC-CMs
      in long QT syndrome type 3 (LQT3) and their response to antiarrhythmic drugs.
      METHODS: Populations of in silico hiPSC-CM models were constructed and calibrated
      for control (n = 1,463 models) and LQT3 caused by INaL channelopathy (n = 1,401
      models), using experimental recordings for late sodium current (INaL) and action
      potentials (APs). Antiarrhythmic drug therapy was evaluated by simulating
      mexiletine and ranolazine multichannel effects. RESULTS: As in experiments, LQT3
      hiPSC-CMs yield prolonged action potential duration at 90% repolarization (APD90)
      (+34.3% than controls) and large electrophysiological variability. LQT3 hiPSC-CMs
      with symptomatic APs showed overexpression of ICaL, IK1, and INaL,
      underexpression of IKr, and increased sensitivity to both drugs compared to
      asymptomatic LQT3 models. Simulations showed that both mexiletine and ranolazine
      corrected APD prolongation in the LQT3 population but also highlighted
      differences in drug response. Mexiletine stops spontaneous APs in more LQT3 hiPSC
      CMs models than ranolazine (784/1,401 vs 53/1,401) due to its stronger action on
      INa. CONCLUSION: In silico simulations demonstrate our ability to recapitulate
      variability in LQT3 and control hiPSC-CM phenotypes, and the ability of
      mexiletine and ranolazine to reduce APD prolongation, in agreement with
      experiments. The in silico models also identify potential ionic mechanisms of
      phenotypic variability in LQT3 hiPSC-CMs, explaining APD prolongation in
      symptomatic vs asymptomatic LQT3 hiPSC-CMs.

PMID- 28756099
TI  - Predictors of ventricular arrhythmia after left ventricular assist device
      implantation: A large single-center observational study.
AB  - BACKGROUND: Ventricular arrhythmias (VAs) are common in patients after left
      ventricular assist device (LVAD) implantation. OBJECTIVE: The purpose of this
      study was to determine the predictors of VAs and their impact on mortality in
      LVAD patients. METHODS: A total of 98 consecutive patients with an implantable
      cardioverter-defibrillator (ICD) (86 [88%] male, mean age 57 +/- 10 years), 57
      [58%] with nonischemic dilated cardiomyopathy) who had received an LVAD between
      May 2011 and December 2013 at our institution were included in the study.
      RESULTS: Mean left ventricular ejection fraction and left ventricular end
      diastolic diameter were 20% +/- 8% and 73 +/- 11 mm, respectively. Seventy-three
      patients (75%) had atrial fibrillation (AF). During the 12 months before LVAD
      implantation, 38 patients (39%) had experienced >=1 episode of VAs (11.5 +/- 20)
      requiring ICD therapies. The number of patients with VAs was comparable among all
      types of ICDs (P = .48). During the 12-month follow-up after LVAD implantation,
      48 patients (49%) experienced >=1 episode of VAs (30 +/- 98) with appropriate ICD
      therapies. The prevalence of VAs was significantly higher among patients with pre
      LVAD VAs compared to those without VAs during the year before LVAD implantation
      (66% vs 38%; P = .008). In a binary multiple logistic regression analysis, pre
      LVAD VAs (hazard ratio 5.36, 95% confidence interval 2.0-14.3; P = .001) and AF
      (hazard ratio 3.1, 95% confidence interval 1.1-11.9; P = .024) predicted post
      LVAD VAs. CONCLUSION: Pre-LVAD VAs and AF predict the occurrence of VAs after
      LVAD implantation. According to the latest data on the negative impact of post
      LVAD VAs on all-cause mortality, further studies should clarify the reasonability
      of maintaining sinus rhythm in patients with AF and/or prophylactic catheter
      ablation of ventricular tachycardias before LVAD implantation.

PMID- 28756100
TI  - Clinical recognition of pure premature ventricular complex-induced cardiomyopathy
      at presentation.
AB  - BACKGROUND: Frequent premature ventricular complexes (PVCs) can induce or worsen
      left ventricular (LV) systolic dysfunction. OBJECTIVE: The purpose of this study
      was to identify the clinical pattern of patients having a "pure PVC-induced"
      cardiomyopathy at presentation. METHODS: This prospective multicenter study
      included 155 consecutive patients (age 55 +/- 12 years, 96 men [62%], 23% +/-12%
      mean PVC burden) with LV dysfunction and frequent PVCs submitted for ablation and
      followed up for at least 12 months. Patients with a previously diagnosed
      structural heart disease (50 [32%]) and those without complete PVC abolition
      during follow-up who did not normalize LV ejection fraction (LVEF) (24 [15%])
      were excluded from the analysis. RESULTS: Of the remaining 81 patients, 41 (51%)
      had a successful sustained ablation, did not have normalized LVEF, and were
      classified as having PVC-worsened nonischemic cardiomyopathy, and 40 (49%) who
      had normalized LVEF were considered as having pure PVC-induced cardiomyopathy.
      The latter group had higher baseline PVC burden (27% +/- 12% vs 12% +/- 8%; P
      <.001), smaller LV end-diastolic diameter (58 +/- 5 mm vs 60 +/- 6 mm; P = .05),
      and shorter intrinsic QRS (105 +/- 12 vs 129 +/- 24 ms; P <.001). Any of the
      following baseline characteristics accurately identified patients who will not
      normalize LVEF after PVC ablation (85% sensitivity, 98% specificity): intrinsic
      QRS >130 ms, baseline PVC burden <17%, and LV end-diastolic diameter >63 mm.
      CONCLUSION: Almost half of patients with frequent PVCs and low LVEF of unknown
      origin normalize LVEF after sustained PVC abolition, and these patients can be
      identified before ablation.

PMID- 28756101
TI  - Autobiographical memory compromise in individuals with alcohol use disorders:
      Towards implications for psychotherapy research.
AB  - It has been found that Autobiographical memory (i.e., memory for personal
      experiences and facts about the self) are not properly maintained in people with
      alcohol-use disorders (AUD). The present paper offers a comprehensive overview of
      findings regarding the consequences of AUD on autobiographical memory. More
      specifically, we offer a theoretical model (the AMAUD Autobiographical Memory and
      Alcohol Use Disorders model) according to which chronic alcohol consumption
      compromises emotion regulation as well as executive control, which maintains the
      construction of autobiographical memory. Compromises in emotional regulation and
      executive functioning can be linked to a weak aspiration to construct detailed
      memories (i.e., autobiographical overgenerality), compromises of subjective
      reliving, anterograde amnesia, negative self-defining memories, and a difficulty
      to mentally project oneself forward in time to generate complex autobiographical
      representations and self-images. By gathering cognitive and clinical aspects of
      autobiographical decline in AUD, this model constitutes a theoretical foundation
      that may lead to a better understanding of this decline. Different clinical
      perspectives are proposed for developing personalized autobiographical memory
      rehabilitation programs for individuals with AUD.

PMID- 28756102
TI  - Trends in typologies of concurrent alcohol, marijuana, and cigarette use among US
      adolescents: An ecological examination by sex and race/ethnicity.
AB  - Substance use during adolescence is a public health concern due to associated
      physical and behavioral health consequences. Such consequences are amplified
      among concurrent substance users. Although sex and racial/ethnic differences in
      single-substance use have been observed, the current literature is inconclusive
      as to whether differences exist in the prevalence of concurrent use. The current
      study used data from the 2011-2014 National Survey on Drug Use and Health to
      examine typologies (single and concurrent patterns) of alcohol, marijuana, and
      cigarette use among current adolescent users age 12-18 by sex and race/ethnicity.
      Participants were 14,667 White, Hispanic, African American, Asian, and Native
      American adolescents. The most common typology was alcohol only, followed by
      concurrent use of alcohol and marijuana. Weighted prevalence estimates indicated
      that adolescent females were more likely to be current users of alcohol only,
      whereas male adolescents were more likely to belong to all other typologies.
      Compared to Whites, racial/ethnic minorities had larger proportions of marijuana
      only users and were generally less likely than or equally likely to be concurrent
      users. One exception was for African American adolescents, who were more likely
      to be alcohol and marijuana users than their White counterparts. Results suggest
      that concurrent substance use is common among U.S. adolescents, making up over
      40% of past-month use, but typologies of use vary by sex and race/ethnicity.
      Preventive interventions should consider all typologies of use rather than only
      single substance exposures and address patterns of use that are most pertinent to
      adolescents based on sex and race/ethnicity.

PMID- 28756103
TI  - Prone to feel guilty: Self-evaluative emotions in alcohol-dependence.
AB  - BACKGROUND: Prior research has repeatedly shown that alcohol-dependence is
      associated with interpersonal difficulties. However, guilt and shame, two crucial
      self-evaluative emotions triggered by the transgression of social norms, have not
      been explored among alcohol-dependent individuals despite their important role in
      psychiatric disorders. The present study thus aimed to investigate whether
      alcohol-dependence is associated with greater proneness to negatively evaluate
      one's own behaviors (guilt) or the entire self (shame). METHODS: 25 alcohol
      dependent individuals (ADI) and 25 matched healthy individuals completed a
      scenario-based inventory (TOSCA-3), requiring from participants to rate the
      extent they will react to each scenario in terms of (contextualized) guilt and
      shame. Participants also completed a list of adjectives related to the frequency
      at which they generally experience (uncontextualized) guilt and shame (PFQ-2).
      RESULTS: When controlling for possible confounds (i.e., depression and anxiety),
      ADI reported greater proneness to experience guilt at the TOSCA-3 (eta2=.22)
      compared to healthy individuals. CONCLUSIONS: This study is the first to show
      that alcohol-dependence is associated with greater contextualized guilt
      proneness, i.e., negative evaluation of one's own behaviors that transgress
      social norms. Therefore, these results reinforce the relevance of social
      disorders in alcohol-dependence and indicate that ADI may benefit of therapeutic
      programs to avoid a generalization of guilt towards shame.

PMID- 28756104
TI  - Drought reduces transmission of Turnip yellows virus, an insect-vectored
      circulative virus.
AB  - Application of a severe water deficit to Arabidopsis thaliana plants infected
      with a mutant of Turnip yellows virus (TuYV, Family Luteoviridae) triggers a
      significant alteration of several plant phenology traits and strongly reduces the
      transmission efficiency of the virus by aphids. Although virus accumulation in
      water-stressed plants was similar to that in plants grown under well-watered
      conditions, virus accumulation was reduced in aphids fed on plants under water
      deficit. These results suggest alteration of the aphid feeding behavior on plants
      under water deficit.

PMID- 28756105
TI  - Comparative efficacy of various endoscopic techniques for the treatment of common
      bile duct stones: a network meta-analysis.
AB  - BACKGROUND AND AIMS: Although various endoscopic techniques have been introduced
      for successful removal of common bile duct (CBD) stones, the optimal method is
      not yet clear. We aimed to compare the efficacy of different endoscopic
      techniques for CBD stone removal. METHODS: We searched for all relevant
      randomized controlled trials published until June 2017, examining the outcomes of
      endoscopic techniques for CBD stone removal, including endoscopic sphincterotomy
      (EST), endoscopic papillary balloon dilatation (EPBD), and EST with balloon
      dilatation (ESBD). A Bayesian network meta-analysis was performed. RESULTS:
      Twenty-five studies with 3726 patients were included in the meta-analysis. ESBD
      had a higher successful rate of stone removal in the first endoscopic session
      than EPBD (odds ratio [OR] [95% credible interval {CrI}], 2.09 [1.07-4.16]).
      Mechanical lithotripsy was less common in ESBD than in EPBD (OR [95% CrI], .45
      [.25-.83]). EPBD revealed a lower risk of bleeding than both EST and ESBD (OR
      [95% CrI], vs EST, .06 [.008-.23]; vs ESBD, .12 [.01-.64]). The pooled incidences
      of bleeding were 3.0% (95% confidence interval [CI], 1.8%-5.2%), 1.1% (95% CI,
      .6%-2.0%), and 2.0% (95% CI, .9%-4.4%) in the EST, EPBD, and ESBD groups,
      respectively. Pancreatitis tended to be more common in EPBD than in both EST and
      ESBD (OR [95% CrI]: vs EST, 1.49 [.84-2.59]; vs ESBD, 1.49 [.61-3.57]).
      CONCLUSION: The efficacy of ESBD in stone removal during the first endoscopic
      session was superior to that of EPBD. Pancreatitis in ESBD and EST tended to be
      less common than in EPBD, although this difference was not statistically
      significant. However, ESBD and EST carried a higher risk of bleeding than EPBD.

PMID- 28756106
TI  - Comprehensive analysis of target genes in zebrafish embryos reveals gbx2
      involvement in neurogenesis.
AB  - It is well established that the gbx2 homeobox gene contributes to the positioning
      of the midbrain-hindbrain boundary (MHB) governing the development of adjacent
      brain regions in vertebrate embryos, but the specific aspects of the gene
      regulatory network regulated by gbx2 during brain development remain unclear. In
      the present study, we sought to comprehensively identify gbx2 target genes in
      zebrafish embryos by microarray analysis around the end of gastrulation, when the
      MHB is established, using transgenic embryos harboring heat-inducible gbx2. This
      analysis revealed that a large number of genes were either upregulated or
      downregulated following gbx2 induction, and the time course of induction differed
      depending on the genes. The differences in response to gbx2 were found by
      functional annotation analysis to be related to the functions and structures of
      the target genes. Among the significantly downregulated genes was her5, whose
      expression in the midbrain was precisely complementary to gbx2 expression around
      the MHB, suggesting that gbx2 expression in the anterior hindbrain restricts her5
      expression to the midbrain. Because her5 represses neurogenesis, gbx2 may
      positively regulate neural development in its expression domain. Indeed, we
      showed further that gbx2 induction upregulated neural marker expression in the
      midbrain. Quantitative PCR analysis revealed that gbx2 upregulated the expression
      of the zebrafish proneural gene ebf2, whereas it repressed notch1a, which
      generally represses neurogenesis. Taken together, these results demonstrate that
      gbx2 not only functions to position the MHB but also regulates neurogenesis in
      the anterior hindbrain.

PMID- 28756107
TI  - S100A12-CD36 axis: A novel player in the pathogenesis of atherosclerosis?
AB  - S100A12 is a member of the S100 family of EF-hand calcium-binding proteins and
      have a variety of intracellular and extracellular activities. It exerts its
      proinflammatory effects by binding to the receptor for advanced glycation end
      products (RAGE) and Toll-like receptor 4 (TLR4). CD36 is a class B scavenger
      receptor that acts as a fatty acid transporter. Both S100A12 and CD36 are
      implicated in vascular inflammation and atherosclerosis. It has recently been
      demonstrated that S100A12 binds with high affinity to CD36. On the other hand,
      RAGE and TLR4 play a key role in the regulation of CD36 expression. These
      observations point to the fact that S100A12 is an interesting molecular target
      for the development of therapeutics. This Cytokine stimulus will focus on the
      possible mechanisms of S100A12-CD36 axis in the pathogenesis of atherosclerosis.

PMID- 28756108
TI  - Diagnostic validity of ICD-10 acute and transient psychotic disorders and DSM-5
      brief psychotic disorder.
AB  - BACKGROUND: Short-lived psychotic disorders are currently classified under "acute
      and transient psychotic disorders" (ATPDs) in ICD-10, and "brief psychotic
      disorder" (BPD) in DSM-5. This study's aim is to review the literature and
      address the validity of ATPDs and BPD. METHOD: Papers published between January
      1993 and December 2016 were identified through searches in Web of Science.
      Reference lists in the located papers provided further sources. RESULTS: A total
      of 295 articles were found and 100 were included in the review. There were only a
      few studies about the epidemiology, vulnerability factors, neurobiological
      correlates and treatment of these disorders, particularly little interest seems
      to exist in BPD. The available evidence suggests that short-lived psychotic
      disorders are rare conditions and more often affect women in early to middle
      adulthood. They also are neither associated with premorbid dysfunctions nor
      characteristic family predisposition, while there seems to be greater evidence of
      environmental factors particularly in developing countries and migrant
      populations. Follow-up studies report a favourable clinical and functional
      outcome, but case identification has proved difficult owing to high rates of
      transition mainly either to schizophrenia and related disorders or, to a lesser
      extent, affective disorders over the short- and longer-terms. CONCLUSIONS:
      Although the lack of neurobiological findings and little predictive power argue
      against the validity of the above diagnostic categories, it is important that
      they are kept apart from longer-lasting psychotic disorders both for clinical
      practice and research. Close overlap between ATPDs and BPD could enhance the
      understanding of these conditions.

PMID- 28756109
TI  - Altered coupling of default-mode, executive-control and salience networks in
      Internet gaming disorder.
AB  - BACKGROUND: Recently, a triple-network model suggested the abnormal interactions
      between the executive-control network (ECN), default-mode network (DMN) and
      salience network (SN) are important characteristics of addiction, in which the SN
      plays a critical role in allocating attentional resources toward the ECN and DMN.
      Although increasing studies have reported dysfunctions in these brain networks in
      Internet gaming disorder (IGD), interactions between these networks, particularly
      in the context of the triple-network model, have not been investigated in IGD.
      Thus, we aimed to assess alterations in the inter-network interactions of these
      large-scale networks in IGD, and to associate the alterations with IGD-related
      behaviors. METHODS: DMN, ECN and SN were identified using group-level independent
      component analysis (gICA) in 39 individuals with IGD and 34 age and gender
      matched healthy controls (HCs). Then alterations in the SN-ECN and SN-DMN
      connectivity, as well as in the modulation of ECN versus DMN by SN, using a
      resource allocation index (RAI) developed and validated previously in nicotine
      addiction, were assessed. Further, associations between these altered network
      coupling and clinical assessments were also examined. RESULTS: Compared with HCs,
      IGD had significantly increased SN-DMN connectivity and decreased RAI in right
      hemisphere (rRAI), and the rRAI in IGD was negatively associated with their
      scores of craving. CONCLUSIONS: These findings suggest that the deficient
      modulation of ECN versus DMN by SN might provide a mechanistic framework to
      better understand the neural basis of IGD and might provide novel evidence for
      the triple-network model in IGD.

PMID- 28756110
TI  - A comparative meta-analysis of neurocognition in first-degree relatives of
      patients with schizophrenia and bipolar disorder.
AB  - OBJECTIVE: Cognitive impairment is a familial and heritable aspect of major
      psychoses and might be a shared vulnerability marker for schizophrenia and BP.
      However, it is not clear whether some aspects of cognitive deficits are uniquely
      associated with risk for specific diagnoses. METHODS: A novel meta-analysis of
      cognitive functions in first-degree relatives of probands with bipolar disorder
      (BP-Rel) and schizophrenia (Sch-Rel) was conducted. Current meta-analysis
      included 20 studies and compared cognitive functions of 1341 Sch-Rel, 939 BP-Rel
      and 1427 healthy controls. RESULTS: Sch-Rel was associated with cognitive
      deficits in all domains (d=0.20-0.58) and BP-Rel underperformed healthy controls
      in processing speed, verbal fluency and speed based executive function tests
      (d=0.33-0.41). Sch-Rel underperformed BP-Rel in general intellectual ability,
      working memory, verbal memory, planning, processing speed and fluency (d=0.24
      0.42). CONCLUSIONS: Inefficiency in processing information and impaired
      processing speed might be common vulnerability factors for major psychoses. On
      the other hand, low performance in accuracy based tasks and deficits in general
      intellectual ability, verbal learning, planning and working memory might be more
      specifically associated with risk for schizophrenia.

PMID- 28756111
TI  - Targeting anxiety to improve quality of life in patients with schizophrenia.
AB  - BACKGROUND: Several studies suggested that anxiety can significantly affect the
      outcome of schizophrenia. Despite this evidence, non-pharmacological
      interventions targeting anxiety are still heterogenous. This study aims to test
      the efficacy of a novel training specifically designed to target anxiety in
      patients with schizophrenia. Innovatively, this training, beyond psychoeducation
      and problem solving, also targets Theory of Mind, as it provides coping
      strategies. METHOD: Twenty-seven outpatients with schizophrenia received a novel
      rehabilitative training targeting anxiety (Anxiety Management Group [AMG])
      combined with a Computer-Assisted Cognitive Remediation (CACR), and twenty
      received CACR plus a control intervention (Control Newspaper discussion Group
      [CNG]). All patients were assessed at baseline and after treatment for quality of
      life, neurocognition and anxiety. RESULTS: After training, patients treated with
      AMG+CACR showed significantly greater improvements on anxiety. A significant
      increase in quality of life was observed only for AMG+CACR group. Moreover, the
      participants' appraisal showed a significant difference between treatment groups
      with higher ratings among patients who received the AMG+CACR. CONCLUSIONS: This
      study thus suggests feasibility and efficacy of the proposed intervention, that
      could be implemented in rehabilitative programs for patients with schizophrenia
      with potential benefits also on disease course and outcome.

PMID- 28756112
TI  - How is psychotherapy training perceived by psychiatric trainees? A cross
      sectional observational study in Europe.

PMID- 28756113
TI  - Preparing for an international student cohort: Making a global impact on nursing.

PMID- 28756114
TI  - Integrating a Statewide HIV Call Line: An Innovative and Tailored Approach for
      Rapid Linkage to HIV Care.
AB  - Only 80% of people living with HIV (PLWH) in the United States are linked to
      care, 40% are engaged in care, and 30% have achieved viral load suppression. We
      addressed linkage to care with a pilot program of a statewide referral call
      center to connect PLWH and their non-HIV specialty providers to HIV care. Callers
      received tailored referrals from nurses trained to work in an existing call
      center, using an electronic assessment tool and a comprehensive HIV provider
      list. Of 122 calls, 85% were from PLWH and 15% from providers calling about a
      patient. Overall, 88 of 104 (84.6%) PLWH and 16 of 18 (88.9%) providers accepted
      care referral, including 13% of PLWH callers without prior HIV care. Results
      indicated that the call center was an acceptable strategy for HIV care referral;
      the use of an existing call center facilitated feasibility of the program and
      improved linkage to HIV care.

PMID- 28756115
TI  - The effects of Lactobacillus reuteri probiotics combined with azithromycin on
      peri-implantitis: A randomized placebo-controlled study.
AB  - PURPOSE: The aim of this randomized placebo-controlled clinical study was to
      investigate the effects of a probiotic tablet containing Lactobacillus reuteri in
      peri-implantitis patients. METHODS: Subjects comprised 30 patients with mild to
      moderate peri-implantitis. A baseline clinical examination and microbiological
      assessment were conducted, followed by an antibiotics treatment (azithromycin,
      500mg, once a day for 3 days). Subjects were divided into probiotic and placebo
      groups. The clinical examination and bacterial sampling were performed 0, 4, 12
      and 24 weeks after the intake of probiotics. The clinical examination included
      probing pocket depth (PPD), bleeding on probing (BOP), the modified plaque index
      (mPI), and modified bleeding index (mBI). The number of bacteria was assessed
      using the PCR-invader method. The Wilcoxon rank-sum test and Wilcoxon signed-rank
      test with Bonferroni corrections were used for data analyses. RESULTS: Although
      the number of bacteria decreased after the administration of azithromycin in both
      groups, they increased again thereafter. No significant difference was observed
      in bacterial numbers between the two groups. Although PPD in the probiotics group
      was significantly lower at 4 and 24 weeks than at 0 weeks (p<0.05), a significant
      decrease did not occur in the placebo group. The mBI score at 24 weeks was
      significantly lower in the probiotics group than in the placebo group (p<0.05).
      No significant difference was observed in BOP or mPI between the two groups.
      CONCLUSION: These results suggested that probiotics prevent inflammation by
      affecting host responses rather than improving microbial flora in peri-implant
      sulci in peri-implantitis patients.

PMID- 28756116
TI  - Selection of antigenic variants of an H5N1 highly pathogenic avian influenza
      virus in vaccinated chickens.
AB  - Vaccination-primed immunity in poultry has been suggested for selection of
      antigenically drifted highly pathogenic avian influenza viruses (HPAIVs). In this
      study, we performed two consecutive passage studies of an H5N1 HPAIV in
      vaccinated chickens, namely, study-I and study-II, to select antigenic variants
      under immune pressure from the vaccination. In study-I, nine consecutive passages
      of a wild-type H5N1 HPAIV were carried out in chickens vaccinated with the
      homologous challenge strain. Antigenically drifted variants with mutations at
      position 179 in the hemagglutinin (HA) were selected after three passages.
      Similarly, in study-II, a vaccination-mediated antigenic variant isolated in
      study-I was used as the vaccine and challenge strain to confirm further antigenic
      drift after updating the vaccine; after the third passage, additional antigenic
      variants with a mutation at position 256 in the HA were selected. Thus, our study
      demonstrated the contribution of vaccination in the selection of antigenic
      variants of H5 HPAIVs in chickens.

PMID- 28756117
TI  - Synaptic integration in cortical inhibitory neuron dendrites.
AB  - Cortical inhibitory interneurons have a wide range of important functions,
      including balancing network excitation, enhancing spike-time precision of
      principal neurons, and synchronizing neural activity within and across brain
      regions. All these functions critically depend on the integration of synaptic
      inputs in their dendrites. But the sparse number of inhibitory cells, their small
      caliber dendrites, and the problem of cell-type identification, have prevented
      fast progress in analyzing their dendritic properties. Despite these challenges,
      recent advancements in electrophysiological, optical and molecular tools have
      opened the door for studying synaptic integration and dendritic computations in
      molecularly defined inhibitory interneurons. Accumulating evidence indicates that
      the biophysical properties of inhibitory neuron dendrites differ substantially
      from those of pyramidal neurons. In addition to the supralinear dendritic
      integration commonly observed in pyramidal neurons, interneuron dendrites can
      also integrate synaptic inputs in a linear or sublinear fashion. In this
      comprehensive review, we compare the dendritic biophysical properties of the
      three major classes of cortical inhibitory neurons and discuss how these cell
      type-specific properties may support their functions in the cortex.

PMID- 28756118
TI  - von Willebrand factor disruption and continuous-flow circulatory devices.
AB  - Bleeding events remain a significant and frequent complication of continuous-flow
      left ventricular assist devices (VADs). von Willebrand factor (VWF) is critical
      to hemostasis by acting as a bridging molecule at sites of vascular injury for
      normal platelet adhesion as well as promoting platelet aggregation under
      conditions of high shear. Clinical and experimental data support a role for
      acquired von Willebrand disease in VAD bleeding episodes caused by shear-induced
      qualitative defects in VWF. Pathologic shear induces VWF unfolding and
      proteolysis of large multimers into smaller less hemostatic multimers via
      ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif,
      member 13). This review outlines the pathobiology of VWF disruption in the
      context of VADs as well as current diagnostic and management strategies of the
      associated acquired von Willebrand disease.

PMID- 28756119
TI  - What to do (or not to do) when randomization is not possible.

PMID- 28756120
TI  - Comparison of two strategies for ex vivo lung perfusion.
AB  - BACKGROUND: Two clinically used strategies for ex vivo lung perfusion (EVLP) were
      compared in a porcine model with respect to lung function, metabolism,
      inflammatory response, oxidative stress, and cell viability. METHODS: Porcine
      lungs (n = 20) were preserved, harvested, and kept cooled for 2 hours. After
      randomization, EVLP was performed using a cellular perfusate and open left atrium
      (COA group) or an acellular perfusate and a closed left atrium (ACA group).
      Oxygenation (partial pressure of arterial oxygen/fraction of inspired oxygen),
      compliance, dead space, weight, and perfusate oncotic pressure were registered
      before and after a 4-hour period of reconditioning. Lung tissue samples were
      collected before and after EVLP for quantitative polymerase chain reaction
      analysis of gene expression for inflammatory markers, measurement of tissue
      hypoxia (hypoxia inducible factor-1alpha) and oxidative stress (ascorbyl
      radical), and viability (trypan blue staining) and lung histopathology. RESULTS:
      In 3 of 10 lungs undergoing EVLP in the ACA group, EVLP was terminated
      prematurely because of severe lung edema and inability to perfuse the lungs.
      There were no significant differences in changes of lung oxygenation or pulmonary
      vascular resistance between groups. Compliance decreased and lung weights
      increased in both groups, but more in the ACA group (p = 0.083 and p = 0.065,
      respectively). There was no obvious difference in gene expression for hypoxia
      inducible factor-1alpha, inflammatory markers, free radicals, or lung injury
      between groups. CONCLUSIONS: Lung edema formation and decreased lung compliance
      occurs with both EVLP techniques but were more pronounced in the ACA group.
      Otherwise, there were no differences in lung function, inflammatory response,
      ischemia/reperfusion injury, or histopathologic changes between the EVLP
      techniques.

PMID- 28756122
TI  - Can we push the boundaries of ABO-incompatible pediatric heart transplantation?

PMID- 28756121
TI  - Distal airway microbiome is associated with immunoregulatory myeloid cell
      responses in lung transplant recipients.
AB  - BACKGROUND: Long-term survival of lung transplant recipients (LTRs) is limited by
      the occurrence of bronchiolitis obliterans syndrome (BOS). Recent evidence
      suggests a role for microbiome alterations in the occurrence of BOS, although the
      precise mechanisms are unclear. In this study we evaluated the relationship
      between the airway microbiome and distinct subsets of immunoregulatory myeloid
      derived suppressor cells (MDSCs) in LTRs. METHODS: Bronchoalveolar lavage (BAL)
      and simultaneous oral wash and nasal swab samples were collected from adult LTRs.
      Microbial genomic DNA was isolated, 16S rRNA genes amplified using V4 primers,
      and polymerase chain reaction (PCR) products sequenced and analyzed. BAL MDSC
      subsets were enumerated using flow cytometry. RESULTS: The oral microbiome
      signature differs from that of the nasal, proximal and distal airway microbiomes,
      whereas the nasal microbiome is closer to the airway microbiome. Proximal and
      distal airway microbiome signatures of individual subjects are distinct. We
      identified phenotypic subsets of MDSCs in BAL, with a higher proportion of
      immunosuppressive MDSCs in the proximal airways, in contrast to a preponderance
      of pro-inflammatory MDSCs in distal airways. Relative abundance of distinct
      bacterial phyla in proximal and distal airways correlated with particular airway
      MDSCs. Expression of CCAAT/enhancer binding protein (C/EBP)-homologous protein
      (CHOP), an endoplasmic (ER) stress sensor, was increased in immunosuppressive
      MDSCs when compared with pro-inflammatory MDSCs. CONCLUSIONS: The nasal
      microbiome closely resembles the microbiome of the proximal and distal airways in
      LTRs. The association of distinct microbial communities with airway MDSCs
      suggests a functional relationship between the local microbiome and MDSC
      phenotype, which may contribute to the pathogenesis of BOS.

PMID- 28756123
TI  - Lymphatic vessel density and VEGF-C expression as independent predictors of
      melanoma metastases.
AB  - INTRODUCTION: In many patients, the clinical behaviour of cutaneous melanoma is
      very difficult to predict by traditional histologic and clinical parameters. This
      study aimed to examine the role of quantitative parameters of tumour
      lymphangiogenesis and vascular endothelial growth factor (VEGF)-C in predicting
      metastatic risk in patients with cutaneous melanoma. METHODS: One hundred
      melanoma specimens were stained with lymphatic-specific antibody D2-40 and with
      anti-VEGF-C antibody. Quantitative parameters of lymphangiogenesis-lymphatic
      vessel density (LVD) and lymphatic vessel area (LVA)-were determined by computer
      assisted morphometric analysis. Moderate or strong staining was assessed as a
      positive expression of VEGF-C in tumour cells. RESULTS: Univariate analysis
      revealed that intratumoural LVD, peritumoural LVD, VEGF-C expression in tumour
      cells, melanoma thickness, Clark level, ulceration, gender and histologic type
      were significant predictors of lymph node metastasis (p = 0.000, p = 0.000, p =
      0.000, p = 0.000, p = 0.005, p = 0.005, p = 0.011 and p = 0.027, respectively).
      No significant association of intratumoural and peritumoural LVA with metastases
      was found. In multivariate analysis, independent predictors of metastatic risks
      were melanoma thickness [odds ratio OR = 1.655, 95% confidence interval (CI)
      1.102-2.484, p = 0.015], intratumoural LVD (OR = 1.086, 95% CI 1.027-1.148, p =
      0.004), peritumoural LVD (OR = 1.050, 95% CI 1.008-1.094, p = 0.020) and a
      positive VEGF-C expression in tumour cells (OR = 20.337, 95% CI 2.579-160.350, p
      = 0.004). CONCLUSIONS: This study identified intratumoural and peritumoural LVD
      and the VEGF-C expression in tumour cells as more significant predictors of
      metastatic risk than melanoma thickness, ulceration and other clinical
      pathological parameters.

PMID- 28756124
TI  - Characterization of brominated flame retardants from e-waste components in China.
AB  - Many studies show that high levels of many toxic metals and persistent and bio
      accumulative chemicals have been found in electronic waste (e-waste) dismantling
      sites and their surrounding environmental media. Both flame-retardant plastic
      housing materials and printed circuit boards (PCBs) could be the major
      contributors. However, relatively little work has focused on the use or content
      of toxic substances and their changing in scrap housing materials and PCBs from
      home appliances. This study evaluated the existence of brominated flame
      retardants (BFRs, including polybrominated diphenyl ethers (PBDEs) and
      Tetrabromobisphenol-A (TBBPA)) in housing plastics and PCBs from home appliances
      collected from various e-waste recyclers in China. These were then analyzed for
      the potential migration of BFRs from the e-waste components into their recycled
      products. The results show that both PBDEs and TBBPA were found with high level
      in most of e-waste samples, indicating that the widespread use of BFRs in home
      appliances are entering into the end-of-life stage. For the plastics samples, CRT
      TVs and LCD monitors should be given priority for the control of BFRs. Regarding
      PBDEs, the dominant congeners of BDE-209 in the plastics samples contributed
      90.72-93.54% to the total concentrations of PBDEs, yet there are large variations
      for PCBs samples: BDE-28, -47, -99, and -153 were also important congeners
      compositions, except for BDE-209. Compared with previous studies, the BFRs
      concentrations in current Chinese e-waste are trending to decline. This study
      also found that BFRs in housing plastics and PCBs will be transferred into the
      recycled products with other purpose use, and the new products could have highly
      enriched capacities for BFRs. The obtained results could be helpful to manage e
      waste and their components properly in order to minimize associated environmental
      and health risks of BFRs, particularly for their further reuse.

PMID- 28756125
TI  - Periphytic biofilms: A promising nutrient utilization regulator in wetlands.
AB  - Low nutrient utilization efficiency in agricultural ecosystems is the main cause
      of nonpoint source (NPS) pollution. Therefore, novel approaches should be
      explored to improve nutrient utilization in these ecosystems. Periphytic biofilms
      composed of microalgae, bacteria and other microbial organisms are ubiquitous and
      form a 'third phase' in artificial wetlands such as paddy fields. Periphytic
      biofilms play critical roles in nutrient transformation between the overlying
      water and soil/sediment, however, their contributions to nutrient utilization
      improvement and NPS pollution control have been largely underestimated. This mini
      review summarizes the contributions of periphytic biofilms to nutrient
      transformation processes, including assimilating and storing bioavailable
      nitrogen and phosphorus, fixing nitrogen, and activating occluded phosphorus.
      Future research should focus on augmenting the nitrogen fixing, phosphate
      solubilizing and phosphatase producing microorganisms in periphytic biofilms to
      improve nutrient utilization and thereby reduce NPS pollution production in
      artificial and natural wetland ecosystems.

PMID- 28756126
TI  - Mechanistic insights of 2,4-D sorption onto biochar: Influence of feedstock
      materials and biochar properties.
AB  - Objective of this study was to investigate the mechanisms of 2,4-Dichlorophynoxy
      acetic acid (2,4-D) sorption on biochar in aqueous solutions. Sorption isotherm,
      kinetics, and desorption experiments were performed to identify the role of
      biochars' feedstock and production conditions on 2,4-D sorption. Biochars were
      prepared from various green wastes (tea, burcucumber, and hardwood) at two
      pyrolytic temperatures (400 and 700 degrees C). The tea waste biochar produced at
      700 degrees C was further activated with steam under a controlled flow. The
      sorption of 2,4-D was strongly dependent on the biochar properties such as
      specific surface area, surface functional groups, and microporosity. The steam
      activated biochar produced from tea waste showed the highest (58.8mgg-1) 2,4-D
      sorption capacity, which was attributed to the high specific surface area (576m2g
      1). The mechanism of 2,4-D removal from aqueous solution by biochar is mainly
      attributed to the formation of heterogeneous sorption sites due to the steam
      activation.

PMID- 28756127
TI  - Removal of nitrite from aqueous solution by Bacillus amyloliquefaciens biofilm
      adsorption.
AB  - A newly verified adsorbent biofilm produced by Bacillus amyloliquefaciens DT was
      investigated for nitrite removal from aqueous solutions. The biofilm's
      characteristics and adsorption mechanism were determined, with results indicating
      that nitrite ions were adsorbed onto the protonated amine sites of biofilm under
      acidic conditions. Analysis of various factors showed that higher nitrite
      adsorption capacities occurred at pH < 3.0 and higher temperatures as well as
      higher initial nitrite concentrations, with a maximum nitrite removal capacity of
      116.84mg/g. Furthermore, nitrite adsorption was well fitted to the pseudo second
      order and Weber-Morris kinetic models, and the Freundlich and Sips isotherm
      models. Simultaneously, thermodynamic analysis demonstrated that nitrite
      adsorption is a spontaneous endothermic process. In summary, the adsorption of
      nitrite was complex, and mainly resulted from electrostatic attraction and
      intraparticle diffusion. Consequently, the B. amyloliquefaciens biofilm can be
      considered as a promising adsorbent for nitrite removal from wastewater.

PMID- 28756128
TI  - Recent developments of post-modification of biochar for electrochemical energy
      storage.
AB  - Biochar is a common byproduct from thermochemical conversion of biomass to
      produce bioenergy. However, the biochar features, such as morphology, porosity
      and surface chemistry, cannot be well controlled in conventional conversion
      approaches, limiting the wide application of raw biochar. Aiming to meet the
      specific requirements, post-modification of raw biochar was frequently conducted
      to improve the quality. In this review, recent developments regarding post
      modification methods of biochar are presented and discussed. Progresses on the
      applications of post modified biochar as electrode materials for supercapacitors
      are intensively summarized. This review aims to reveal the key factors that
      affecting the performance of biochar-based supercapacitors, and provide guidance
      for rationalizing the modification methods to expand the applications of biochar
      based functional materials in supercapacitors.

PMID- 28756129
TI  - Outcomes of threatened abortions after anticoagulation treatment to prevent
      recurrent pregnancy loss.
AB  - We aimed to determine the outcome of threatened abortion in women treated with
      low-molecular weight heparin (LMWH) for recurrent pregnancy loss (RPL). Data of
      women with RPL who experienced threatened abortion while taking LMWH between 2007
      and 2016 were retrospectively reviewed. All patients received the LMWH,
      enoxaparin (40 mg). Thrombophilia was present in 38 (33.3%) women, including 11
      (9.6%) with antiphospholipid syndrome (APLS). The overall live birth rate was
      58.8% (67/114). Live birth rates were 87.2% (41/47 patients) and 38.8% (26/67
      patients) among those who discontinued versus those who continued LMWH treatment,
      respectively (P < 0.0001). Among APLS patients, live births resulted in eight of
      the nine women who continued LMWH. In multivariate analysis, discontinuation of
      LMWH was the only significant predictor of live birth outcome (P < 0.0001).
      Thrombophilia, presence of subchorionic haematoma, and severity of bleeding were
      not found to be associated with live birth outcomes. For women with threatened
      abortions, continuation of LMWH indicated to prevent RPL was negatively
      associated with live birth rates. Therefore, we support its discontinuation in
      this setting. Among women with APLS, LMWH continuation resulted in a relatively
      high live birth rate; we advocate against its withdrawal in this subset of
      patients.

PMID- 28756130
TI  - Inositol supplementation in women with polycystic ovary syndrome undergoing
      intracytoplasmic sperm injection: a systematic review and meta-analysis of
      randomized controlled trials.
AB  - Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disease that
      involves menstrual dysfunction and reproductive difficulty, as well as metabolic
      problems. The aim of this study was to assess the effectiveness of myo-inositol
      (MYO) and d-chiro-inositol (DCI) on improving oocyte or embryo quality and
      pregnancy rates for women with PCOS undergoing intracytoplasmic sperm injection
      (ICSI). We searched the Web of Knowledge, MEDLINE, EMBASE, Pubmed, Scopus and
      Cochrane databases for all articles published in any language up to March 2017.
      The selection criteria were as follows: (population) patients with PCOS;
      (intervention) treatment with inositol (MYO, DCI, or both, with any dose and any
      duration) in conjunction with an ovulation-inducing agent versus the ovulation
      inducing agent alone; (outcome) oocyte and embryo quality; (study design)
      randomized controlled trials. Of 76 identified studies, eight RCTs were included
      for analysis comprising 1019 women with PCOS. MYO supplementation was
      insufficient to improve oocyte quality (OR 2.2051; 95% CI 0.8260 to 5.8868),
      embryo quality (OR 1.6231, 95% CI 0.3926 to 6.7097), or pregnancy rate (OR
      1.2832, 95% CI 0.8692 to 1.8944). Future studies of appropriate dose, size and
      duration of DCI are vital to clarify its the role in the management of PCOS.

PMID- 28756131
TI  - Platelet-rich plasma promotes the development of isolated human primordial and
      primary follicles to the preantral stage.
AB  - This study aimed to assess the effects of platelet-rich plasma (PRP) on growth
      and survival of isolated early human follicles in a three-dimensional culture
      system. After fresh and vitrified-warmed ovarian tissue was digested, isolated
      early preantral follicles and ovarian cells were separately encapsulated in 1%
      alginate (w/v). The encapsulated follicles and ovarian cells were cultured
      together in a medium supplemented with foetal bovine serum (FBS), PRP, PRP + FBS,
      or human serum albumin (HSA) for 10 days. Growth and survival of the follicles
      were assessed by measurement of diameter and staining with trypan blue.
      Follicular integrity was assessed by histological analysis. After culturing, all
      follicles increased in size, but growth rate was greater in follicles isolated
      from fresh samples than those from vitrified-warmed ones (P < 0.001). Similarly,
      follicular viability of fresh samples after culturing was higher than that of
      vitrified-warmed ones. The growth and survival rates of follicles from both fresh
      and vitrified groups cultured in PRP supplemented media were significantly higher
      than those of other groups (growth P < 0.001 and survival P < 0.05, in both
      groups). In conclusion, media supplementation with PRP can better support
      viability and growth of isolated human early preantral follicles in vitro.

PMID- 28756132
TI  - Effects of depression, diabetes distress, diabetes self-efficacy, and diabetes
      self-management on glycemic control among Chinese population with type 2 diabetes
      mellitus.
AB  - AIM: To examine the direct and indirect effects of depression, diabetes distress,
      diabetes self-efficacy and diabetes self-management on glycemic control among a
      group of T2DM patients in China. METHOD: A convenience sample of 254 participants
      were selected from three outpatient departments in Beijing, China. They were
      surveyed using a self-administered questionnaire. Diabetes-related information
      was retrieved from their medical records. Descriptive statistics, independent
      student t tests, Chi-square tests, correlation analyses and Generalized
      Structural Equation Modeling were used. RESULTS: Only 91 (35.82%) participants
      achieved optimal glycemic control of HbA1c<7.0% (53mmol/mol). Only diabetes self
      management had a direct effect on glycemic control (OR=0.95, P<0.001). Depression
      and diabetes distress had only indirect effects on glycemic control through both
      diabetes self-efficacy and diabetes self-management. Diabetes self-efficacy only
      had an indirect effect on glycemic control through diabetes self-management.
      CONCLUSIONS: Glycemic control among Chinese population with T2DM was suboptimal.
      Future interventions should focus on decreasing depressive symptoms and diabetes
      distress levels, and, therefore, improve diabetes self-efficacy and self
      management practices and, ultimately, reach the optimal goal of glycemic control.

PMID- 28756133
TI  - Effect of nurse-led randomised control trials on cardiovascular risk factors and
      HbA1c in diabetes patients: A meta-analysis.
AB  - A systematic review and meta-analysis identified 42 randomised control trials
      comparing a nurse-led intervention with 'usual care' to quantify their effect on
      glycated haemoglobin (HbA1c) and major cardiovascular risk factors in diabetes
      patients. All relevant databases were systematically searched for publications to
      February 2016: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE
      and Cumulative Index to Nursing & Allied Health Literature (CINAHL). The 42
      trials recruited 9955 diabetes patients (5022 randomised to intervention and 4933
      to 'usual care'). For patients receiving the nurse-led intervention, compared
      with 'usual care', there were small but significant mean reductions for HbA1c [
      0.28%; 95% CI -0.38%, -0.18%; p-value<0.0001, n=6920] and serum triglyceride
      levels [-0.27mmol/L; 95% CI -0.49, -0.06; p=0.01, n=1169], and a greater
      proportion of patients stopped smoking [risk ratio=2.70; 95% CI 1.35, 5.43;
      p=0.005, n=1890 patients]. Mean reductions for systolic [-1.84mmHg; 95% CI -3.97,
      -0.10; p=0.06, 4241 patients] and diastolic [-0.95mmHg; 95% CI -2.15, -0.25;
      p=0.12, 3811 patients] blood pressures trended towards significance. There were
      no significant mean reductions for body mass index or serum cholesterol. Nurse
      led interventions produced greater improvements than 'usual care' for HbA1c,
      serum triglyceride and smoking cessation and support an increased independent
      role for nurses in diabetes management.

PMID- 28756134
TI  - Molecular phylogeny of Pasiphaeidae (Crustacea, Decapoda, Caridea) reveals
      systematic incongruence of the current classification.
AB  - Caridean shrimps constitute one of the most diverse groups of decapod
      crustaceans, notwithstanding their poorly resolved infraordinal relationships.
      One of the systematically controversial families in Caridea is the predominantly
      pelagic Pasiphaeidae, comprises 101 species in seven genera. Pasiphaeidae species
      exhibit high morphological disparity, as well as ecological niche width,
      inhabiting shallow to very deep waters (>4000m). The present work presents the
      first molecular phylogeny of the family, based on a combined dataset of six
      mitochondrial and nuclear gene markers (12S rDNA, 16S rDNA, histone 3, sodium
      potassium ATPase alpha-subunit, enolase and ATP synthase beta-subunit) from 33
      species belonged to six genera of Pasiphaeidae with 19 species from 12 other
      caridean families as outgroup taxa. Maximum likelihood and Bayesian inference
      analyses conducted on the concatenated dataset of 2265bp suggest the family
      Pasiphaeidae is not monophyletic, with Psathyrocaris more closely related to
      other carideans than to the other five pasiphaeid genera included in this
      analysis. Leptochela occupies a sister position to the remaining genera and is
      genetically quite distant from them. At the generic level, the analysis supports
      the monophyly of Pasiphaea, Leptochela and Psathyrocaris, while Eupasiphae is
      shown to be paraphyletic, closely related to Parapasiphae and Glyphus. The
      present molecular result strongly implies that certain morphological characters
      used in the present systematic delineation within Pasiphaeidae may not be
      synapomorphies and the classification within the family needs to be urgently
      revised.

PMID- 28756136
TI  - Addressing the best treatment for non-clear cell renal cell carcinoma: A meta
      analysis of randomised clinical trials comparing VEGFR-TKis versus mTORi-targeted
      therapies.
AB  - AIM: Non-clear cell renal cell carcinoma (nccRCC) tumours include a heterogeneous
      group of malignancies that profoundly differ in terms of morphology, genetic
      profile, clinical behaviour and prognosis. The optimal treatment algorithm for
      nccRCC is still unknown and derived mainly from evidence available for ccRCC,
      being therefore represented by targeted agents against vascular endothelial
      growth factor and mammalian target of rapamycin (mTOR) pathways. We aimed to
      compare the efficacy of vascular endothelial growth factor receptor tyrosine
      kinase inhibitors (VEGFR-TKis) and mTOR inhibitors (mTORi) for the treatment of
      nccRCC patients. METHODS: Searching the MEDLINE/PubMed, Cochrane Library and
      American Society of Clinical Oncology Meeting abstracts prospective studies were
      identified. Data extraction was conduced according to the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses statement. The measured outcomes
      were progression-free survival (PFS), overall survival (OS) and the overall
      response rate (ORR). RESULTS: Four randomised controlled trials were selected for
      final analysis, with a total of 332 patients evaluable for PFS. Treatment with
      TKi significantly reduced the risk of progression compared with mTORi (hazard
      ratio [HR] = 0.71; 95% confidence interval [CI] 0.60-0.84; p < 0.0001). This
      difference remained significant when sunitinib was compared with everolimus in
      first-line setting (HR = 0.67; 95% CI, 0.56-0.80; p < 0.00001). In the 332
      patients evaluable for OS, no significant difference was found between TKi and
      mTORi (HR = 0.86; 95% CI, 0.67-1.12; p = 0.27). In the 176 evaluable patients,
      TKis therapy did not improve the ORR when compared with mTORi (relative risk [RR]
      = 2.21; 95% CI, 0.87-5.60; p = 0.09), even if treatment with sunitinib doubled
      the probability of achieving a tumour response. CONCLUSIONS: Treatment with TKis
      significantly improves PFS, but not OS, when compared with mTORi. Moreover,
      sunitinib as first-line therapy reduces the risk of progression compared with
      everolimus; therefore, supporting the standard treatment paradigm broadly used
      for ccRCC patients. The relatively modest efficacy of available targeted
      therapies reinforces the need of future histology based, molecular driven
      therapeutic paradigm.

PMID- 28756137
TI  - Survival of patients with advanced metastatic melanoma: the impact of novel
      therapies-update 2017.
AB  - The treatment of metastatic melanoma is still undergoing a process of major
      change. The two most important novel therapeutic strategies, selective kinase
      inhibitors and immune checkpoint blockers, both significantly prolong survival
      times of patients with advanced metastatic disease. Different agents, dose
      regimens and combinations have been tested against each other vigorously within
      these two groups. However, results from prospective head-to-head comparative
      studies of both strategies are still lacking. We performed an exploratory
      analysis of survival data from selected clinical trials representative for the
      new treatment strategies in advanced metastatic melanoma. Eighty-three Kaplan
      Meier survival curves from 25 trials were digitised and grouped by therapeutic
      strategy and treatment line. For each of these groups, mean survival curves were
      generated for progression-free (PFS) and overall survival (OS) by weighted
      averaging. Survival curves grouped together by therapeutic strategy revealed a
      high concordance, particularly in the first-line setting. For kinase inhibitors,
      the most favourable PFS and OS in all therapy lines were observed for combined
      BRAF plus MEK inhibition. For immune checkpoint inhibitors, combined PD-1 plus
      CTLA-4 inhibition demonstrated the best survival outcome in all categories except
      for OS in first-line therapy. For the latter, combined PD-1 plus CTLA-4
      inhibition showed similar outcomes as single-agent PD-1 inhibition. Comparison of
      kinase inhibitors and checkpoint blockers revealed a superiority of combined BRAF
      plus MEK inhibition within the first 6 months, later changing to a superiority of
      PD-1 blockers alone or in combination with CTLA-4 blockers. These results need
      confirmation by prospective clinical trials.

PMID- 28756138
TI  - Mutant p53 as a target for cancer treatment.
AB  - TP53 (p53) is the single most frequently altered gene in human cancers, with
      mutations being present in approximately 50% of all invasive tumours. However, in
      some of the most difficult-to-treat cancers such as high-grade serous ovarian
      cancers, triple-negative breast cancers, oesophageal cancers, small-cell lung
      cancers and squamous cell lung cancers, p53 is mutated in at least 80% of
      samples. Clearly, therefore, mutant p53 protein is an important candidate target
      against which new anticancer treatments could be developed. Although
      traditionally regarded as undruggable, several compounds such as p53 reactivation
      and induction of massive apoptosis-1 (PRIMA-1), a methylated derivative and
      structural analogue of PRIMA-1, i.e. APR-246, 2-sulfonylpyrimidines such as
      PK11007, pyrazoles such as PK7088, zinc metallochaperone-1 (ZMC1), a third
      generation thiosemicarbazone developed by Critical Outcome Techonologies Inc.
      (COTI-2) as well as specific peptides have recently been reported to reactive
      mutant p53 protein by converting it to a form exhibiting wild-type properties.
      Consistent with the reactivation of mutant p53, these compounds have been shown
      to exhibit anticancer activity in preclinical models expressing mutant p53. To
      date, two of these compounds, i.e. APR-246 and COTI-2 have progressed to clinical
      trials. A phase I/IIa clinical trial with APR-246 reported no major adverse
      effect. Currently, APR-246 is undergoing a phase Ib/II trial in patients with
      advanced serous ovarian cancer, while COTI-2 is being evaluated in a phase I
      trial in patients with advanced gynaecological cancers. It remains to be shown
      however, whether any mutant p53 reactivating compound has efficacy for the
      treatment of human cancer.

PMID- 28756135
TI  - ESCORTing proteins directly from whole cell-lysate for single-molecule studies.
AB  - We have developed a method for Enzymatic Sortase-assisted Covalent Orientation
      specific Restraint Tethering (ESCORT) recombinant proteins onto surfaces directly
      from cell-lysate. With an improved surface passivation method, we obviate the
      cumbersome purification steps even for single molecule studies that demand high
      purity in the sample. We demonstrated high-specificity of the method, high
      passivity of the surface and uncompromised functional integrity of anchored
      proteins using single molecule fluorescence and force-mapping. We anticipate that
      this method will substantially reduce the investment by way of time, money and
      energy in the area of single molecule studies.

PMID- 28756139
TI  - A universal phage display system for the seamless construction of Fab libraries.
AB  - The construction of Fab phage libraries requires the cloning of domains from both
      the light and the heavy chain of antibodies. Despite the advent of powerful
      strategies such as splicing-by-overlap extension PCR, obtaining high quality
      libraries with excellent coverage remains challenging. Here, we explored the use
      of type IIS restriction enzymes for the seamless cloning of Fab libraries. We
      analyzed human, murine and rabbit germline antibody repertoires and identified
      combinations of restriction enzymes that exhibit very few or no recognition sites
      in the antibody sequences. We describe three phagemid vectors, pUP-22Hb, pUP-22Mc
      and pUP-22Rc, which were employed for cloning the Fab repertoire of these hosts
      using BsmBI and SapI (human) or SapI alone (mouse and rabbit). Using human serum
      albumin as a model immunization, we built a mouse/human chimeric Fab library and
      a mouse Fab library in a single step ligation and successfully panned multiple
      cognate antibodies. The overall process is highly scalable and faster than PCR
      based techniques, with a Fab insertion success rate of around 80%. By using
      carefully chosen overhangs on each end of the antibody domains, this approach
      paves the way to the universal, sequence- and vector-independent cloning and
      reformatting of antibody libraries.

PMID- 28756140
TI  - Naloxone affordability measures needed.

PMID- 28756141
TI  - Evaluation of the Patient Health Questionnaire-2 as a Screening Tool for
      Depression during the Acute Stroke Admission.
AB  - BACKGROUND: The ideal time to screen for poststroke depression remains uncertain.
      We evaluated the 2-item Patient Health Questionnaire (PHQ-2) as a screening tool
      for depression during the acute stroke admission by determining the prevalence of
      positive depression screen during admission and by calculating the level of
      agreement between positive screens during admission and follow-up. METHODS: This
      was a retrospective cohort of adult stroke survivors discharged January to
      December 2013 with principal discharge diagnosis of acute ischemic stroke or
      intracerebral hemorrhage. Depression screening was systematically performed
      during the hospital admission using the PHQ-2. The 9-item Patient Health
      Questionnaire (PHQ-9), which includes the PHQ-2, was completed by patients at
      outpatient follow-up. RESULTS: The study cohort consisted of 337 patients with
      mean age of 66.3 years. Median time from admission to PHQ-2 was 3 days
      (interquartile range 1-4 days). The screen was positive for depression in 4.7%
      (95% confidence interval 2.7%-7.6%) of patients. Of the 150 patients with PHQ-9
      data at outpatient follow up, 19.3% screened positive for depression. In both the
      inpatient setting and at outpatient follow-up, the prevalence of a positive
      depression screen was similar between patients with and without a history of
      depression or antidepressant use. CONCLUSIONS: Systematic screening for
      depression using PHQ-2 during hospitalization for acute stroke identified few
      patients. Most patients with depressive symptoms were identified only at the time
      of outpatient follow-up. Further study is needed to evaluate the usefulness of
      other depression screens for stroke patients in the acute hospital setting and
      the optimal timing for depression screening after stroke.

PMID- 28756142
TI  - Pathologic Study of Intracranial Large Artery Atherosclerosis in 7260 Autopsy
      Cases.
AB  - BACKGROUND: Atherosclerotic changes in the cerebral arteries may differ with era
      of birth. Herein, we analyzed the chronological changes of intracranial
      atherosclerosis in consecutive autopsy cases. METHODS: A total of 7260 autopsy
      cases from 1972 to 2014 were analyzed. Severity of atherosclerosis was classified
      using a semi-quantitative scale of pathologic observation of each artery after
      formalin fixation: 0 = no stenosis; .5 = fatty streaks but no stenosis; 1 = <50%
      stenosis; 2 = 50%-90% stenosis; 3 = >=90% stenosis. The bilateral vertebral,
      anterior, middle, and posterior cerebral arteries and the basilar artery were
      scored. The sum of each individual was defined and compared by age at death, sex,
      and era of birth. RESULTS: The atherosclerosis score increased with age at death,
      as follows: age in the 50s, 0 [0-2]; 60s, 3 [.5-7]; 70s, 5 [2-9.5]; 80s, 6.5 [3.5
      11.5]; 90s, 7.75 [4-12]; and 100s, 8 [5.5-13.5] (median value [interquartile
      range], P< .0001). The percentage of cases with a score of 2 or 3 in each artery
      also increased with age (P< .0001). Atherosclerosis score was higher in men than
      women in their 60s at death, and was higher in women than men in their 80s and
      90s at death. In each age at death group (from 60s to 100s), the score declined
      with later year of birth (P < .05). CONCLUSIONS: Intracranial atherosclerosis
      advances with age and is more severe in subjects born earlier.

PMID- 28756143
TI  - Relationship between Grooming Performance and Motor and Cognitive Functions in
      Stroke Patients with Receiver Operating Characteristic Analysis.
AB  - BACKGROUND: This study aimed to elucidate the relationship between grooming
      performance of stroke patients and various motor and cognitive functions and to
      examine the cognitive and physical functional standards required for grooming
      independence. METHODS: We retrospectively analyzed the data of 96 hospitalized
      patients with first stroke in a rehabilitation hospital ward. Logistic regression
      analysis and receiver operating characteristic curves were used to investigate
      the related cognitive and motor functions with grooming performance and to
      calculate the cutoff values for independence and supervision levels in grooming.
      RESULTS: For analysis between the independent and supervision-dependent groups,
      the only item with an area under the curve (AUC) of .9 or higher was the Berg
      Balance Scale, and the calculated cutoff value was 41/40 (sensitivity, 83.6%;
      specificity, 87.8%). For analysis between the independent-supervision and
      dependent groups, the items with an AUC of .9 or higher were the Simple Test for
      Evaluating Hand Function (STEF) on the nonaffected side, Vitality Index (VI), and
      FIM(r) cognition. The cutoff values were 68/67 for the STEF (sensitivity, 100%;
      specificity, 72.2%), 9/8 points for the VI (sensitivity, 92.3%; specificity,
      88.9%), and 23/22 points for FIM(r) cognition (sensitivity, 91.0%; specificity,
      88.9%). CONCLUSIONS: Our results suggest that upper-extremity functions on the
      nonaffected side, motivation, and cognitive functions are particularly important
      to achieve the supervision level and that balance is important to reach the
      independence level. The effective improvement of grooming performance is possible
      by performing therapeutic or compensatory intervention on functions that have not
      achieved these cutoff values.

PMID- 28756144
TI  - Blood Oxygenation Level-Dependent Functional Magnetic Resonance Imaging in Early
      Days: Correlation between Passive Activation and Motor Recovery After Unilateral
      Striatocapsular Cerebral Infarction.
AB  - OBJECTIVE: This study aimed to investigate the correlation between the functional
      magnetic resonance imaging (fMRI) pattern and the motor function recovery of an
      affected limb during the passive movement of the affected limb at an early stage
      of the striatocapsular infarction (SCI). METHODS: A total of 17 patients with an
      acute stage of SCI and 3 healthy volunteers as controls were included in this
      study. fMRI scans of passive movement were performed on the affected limbs of
      stroke patients within 1 week of onset. Follow-ups were carried out for the motor
      functions of the affected limbs (before fMRI scan, 1 month, and 3 months after
      the scan). RESULTS: The control group showed that the activation was mainly
      located in the contralateral sensorimotor cortex (SMC) and the bilateral
      supplementary motor area (SMA). The fMRI scan region of interest for stroke
      patients can be divided into 3 types: type I includes mainly the affected side,
      bilateral SMC, and SMA with activation; type II includes SMC on the affected side
      and SMA with activation; type III includes only SMC on the affected side or M1
      with activation. The recovery of type I patients was better and faster, while the
      recovery of type II patients was better but slower, but recovery of type III
      patients was poorer and slower. CONCLUSIONS: Multiple cortical activation
      patterns were noted during the passive movement of the affected limbs at an early
      stage of SCI, and a correlation was found between the different activation
      patterns and the clinical prognosis of patients.

PMID- 28756145
TI  - Limb-Shaking Transient Ischemic Attack Induced by Middle Cerebral Artery
      Dissection after Lung Surgery.
AB  - We report a case of limb-shaking transient ischemic attack (TIA) caused by a
      dissection of the middle cerebral artery (MCA) following lung surgery under
      general anesthesia. An 81-year-old male patient who underwent lobectomy for lung
      cancer suddenly developed transient shaking movements of the neck and the left
      upper distal limb on postoperative day 1. On the basis of the double-barrel
      appearance of the right M1 segment of the MCA, a diagnosis of MCA dissection was
      made. Physicians should be aware that limb-shaking TIA is sometimes caused by MCA
      dissection and could be precipitated by any condition, including lung surgery
      under general anesthesia.

PMID- 28756146
TI  - Two-Year Experience Implementing a Curriculum to Improve Residents' Patient
      Centered Communication Skills.
AB  - OBJECTIVES: Surgery milestones from The Accreditation Council for Graduate
      Medical Education have encouraged a focus on training and assessment of
      residents' nontechnical skills, including communication. We describe our 2-year
      experience implementing a simulation-based curriculum, results of annual
      communication performance assessments, and resident evaluations. DESIGN: Eight
      quarterly modules were conducted on various communication topics. Former patient
      volunteers served as simulation participants (SP) who completed annual
      assessments using the Communication Assessment Tool (CAT). During these 2
      modules, communication skills were assessed in the following standardized
      scenarios: (1) delivering bad news to a caregiver of a patient with postoperative
      intracerebral hemorrhage and (2) primary care gallstone referral with
      contraindications for cholecystectomy. SP-CAT ratings were evaluated for
      correlations by individual and associations with trainee and SP characteristics.
      Surgical patient experience surveys are evaluated during the curriculum. SETTING:
      Independent academic medical center surgical simulation center. PARTICIPANTS:
      Twenty-five surgery residents per year in 2015 to 2017. RESULTS: Residents have
      practiced skills in a variety of scenarios including bad news delivery, medical
      error disclosure, empathic communication, and end-of-life conversations.
      Residents report positive learning experiences from the curriculum (90% graded
      all modules A/A+). Confidence ratings rose following each module (p < 0.001) and
      in the second year (p < 0.001). Annual assessments yielded insights into skills
      level, and relationships to resident confidence levels and traits. Communication
      scores were not associated with resident gender or postgraduate year. Over the
      course of the curriculum implementation, surgical patients have reported that
      doctors provided explanations with improved clarity (p = 0.042). CONCLUSIONS: The
      simulation-based SP-CAT has shown initial evidence of usability, content
      validity, relationships to observed communication behaviors and residents' skills
      confidence. Evaluations of different scenarios may not be correlated for
      individuals over time. The communication curriculum paralleled improvements in
      patient experience concerning surgeons' clear explanations. An ongoing surgery
      resident communication curriculum has numerous educational, assessment, and
      institutional benefits.

PMID- 28756147
TI  - Defining and Measuring Decision-Making for the Management of Trauma Patients.
AB  - BACKGROUND: Effective management of trauma patients is heavily dependent on sound
      judgment and decision-making. Yet, current methods for training and assessing
      these advanced cognitive skills are subjective, lack standardization, and are
      prone to error. This qualitative study aims to define and characterize the
      cognitive and interpersonal competencies required to optimally manage injured
      patients. METHODS: Cognitive and hierarchical task analyses for managing unstable
      trauma patients were performed using qualitative methods to map the thoughts,
      behaviors, and practices that characterize expert performance. Trauma team
      leaders and board-certified trauma surgeons participated in semistructured
      interviews that were transcribed verbatim. Data were supplemented with content
      from published literature and prospectively collected field notes from
      observations of the trauma team during trauma activations. The data were coded
      and analyzed using grounded theory by 2 independent reviewers. RESULTS: A
      framework was created based on 14 interviews with experts (lasting 1-2 hours
      each), 35 field observations (20 [57%] blunt; 15 [43%] penetrating; median Injury
      Severity Score 20 [13-25]), and 15 literary sources. Experts included 11 trauma
      surgeons and 3 emergency physicians from 7 Level 1 academic institutions in North
      America (median years in practice: 12 [8-17]). Twenty-nine competencies were
      identified, including 17 (59%) related to situation awareness, 6 (21%) involving
      decision-making, and 6 (21%) requiring interpersonal skills. Of 40 potential
      errors that were identified, root causes were mapped to errors in situation
      awareness (20 [50%]), decision-making (10 [25%]), or interpersonal skills (10
      [25%]). CONCLUSIONS: This study defines cognitive and interpersonal competencies
      that are essential for the management of trauma patients. This framework may
      serve as the basis for novel curricula to train and assess decision-making
      skills, and to develop quality-control metrics to improve team and individual
      performance.

PMID- 28756148
TI  - Ginsenoside Rg2 protects PC12 cells against beta-amyloid25-35-induced apoptosis
      via the phosphoinositide 3-kinase/Akt pathway.
AB  - Alzheimer's disease (AD) is one of the most debilitating neurodegenerative
      diseases in an aging population. Excessive accumulation of beta-amyloid (Abeta)
      has been proposed as a pivotal event in the pathogenesis of AD. Ginsenoside Rg2
      has been reported to exert neuroprotective effects. However, the underlying
      mechanism for its neuroprotection is not well-understood. In this study, we
      investigated the protective effects of ginsenoside Rg2 on Abeta25-35-induced
      neurotoxicity in PC12 cells and identified a potential molecular signaling
      pathway involved. The results showed that pretreatment of PC12 cells with
      ginsenoside Rg2 followed by Abeta25-35 increased cell viability in a
      concentration-dependent manner compared to cells that were not pretreated. In
      addition, ginsenoside Rg2 pretreatment attenuated Abeta25-35-induced increases in
      the release of lactate dehydrogenase, the intracellular calcium concentration,
      and levels of reactive oxygen species. Pretreatment with ginsenoside Rg2
      increased the Bcl-2/Bax ratio. Moreover, ginsenoside Rg2 attenuated the cleavage
      of caspase-3 induced by Abeta25-35 thereby improving cell survival. Ginsenoside
      Rg2 significantly enhanced the phosphorylation of Akt in PC12 cells.
      Additionally, pretreatment with the phosphoinositide 3-kinase (PI3K) inhibitor,
      LY294002, completely abolished the protective effects of ginsenoside Rg2 against
      Abeta25-35-induced neuronal cell apoptosis. These findings unambiguously
      suggested that the protective effect of ginsenoside Rg2 against Abeta25-35
      induced apoptosis in PC12 cells was associated with enhancement of the PI3K/Akt
      signaling pathway.

PMID- 28756149
TI  - Anticancer potential of Amaryllidaceae alkaloids evaluated by screening with a
      panel of human cells, real-time cellular analysis and Ehrlich tumor-bearing mice.
AB  - In this study, twenty-two Amaryllidaceae alkaloids were screened for their
      anticancer potential. All isolates were evaluated for antiproliferative
      activities on a panel of 17 human cell types of different tissue origin using WST
      1 assay. In addition, we determined the antiproliferative effect with a real-time
      cell analysis xCELLigence system. Thereafter, to evaluate the barely known in
      vivo anticancer potential of the most potent molecule haemanthamine, a
      preliminary study was performed using an Ehrlich tumor-bearing mice model. The
      results showed that haemanthamine, lycorine and haemanthidine exerted the highest
      antiproliferative activity. The mean growth percent (GP) value after a single
      dose 10 MUM treatment was for haemanthamine 21%, for lycorine 21% and for
      haemanthidine 27% that of untreated control cells (100%). Furthermore,
      haemanthamine, lycorine and haemanthidine exhibited significant cytotoxicities
      against all the tested cell lines with individual IC50 values in the micromolar
      range. Dynamic real-time measures of impedance by xCELLigence indicated that
      these three compounds suppress cell proliferation after 10 h of treatment at a
      concentration of 10 MUM or higher. Regrettably, in a follow-up in vivo antitumor
      activity study, haemanthamine showed no statistically significant reduction in
      the tumor size with no prolongation of survival time of Ehrlich tumor-bearing
      mice. Taken together, these results provide a new clue and guidance for
      exploiting Amaryllidaceae alkaloids as anticancer agents.

PMID- 28756150
TI  - A marine sponge alkaloid derivative 4-chloro fascaplysin inhibits tumor growth
      and VEGF mediated angiogenesis by disrupting PI3K/Akt/mTOR signaling cascade.
AB  - Tumor angiogenesis and PI3K/Akt/mTOR pathway are two major molecular objectives
      for the treatment and management of breast cancer. Here we first time report the
      molecular mechanism of a marine sponge alkaloid derivative 4-chloro fascapysin (4
      CF) for its anticancer and antiangiogenesis potential. It simultaneously targets
      multiple cancer and angiogenesis dynamics, such as proliferation, chemotaxis cell
      migration, and invasion, growth factors signaling cascade, autophagy and
      apoptosis in HUVEC and MDAMB-231 breast cancer cells. It inhibited the VEGF
      mediated microvessel sprouting and blood vessel formation in the matrigel plug of
      C57/BL6J mice. It inhibits the tumor growth in ET (solid) mouse tumor model. It
      significantly inhibited cell survival through PI3K/Akt/mTOR pathway, with
      attendant effects on key pro-angiogenesis factors like HIF-1alpha, eNOS and MMP
      2/9. The cytotoxicity of 4-CF was reversed by co-treatment with the VEGF and Akt
      inhibitors sunitinib and perifosine, respectively or by the addition of
      neutralizing VEGF antibodies. The apoptotic potential of 4-CF was through
      mitochondrial dependent as illustrated through loss of mitochondrial membrane
      potential. The safety profile of 4-CF was acceptable as it exhibits five times
      high cytotoxic IC50 value in normal cells as well as no apparent toxicities in
      experimental tumor mice at therapeutic doses.

PMID- 28756151
TI  - Polyionic complexes of butyrylcholinesterase and poly-l-lysine-g-poly(ethylene
      glycol): Comparative kinetics of catalysis and inhibition and in vitro
      inactivation by proteases and heat.
AB  - We previously reported that recombinant human butyrylcholinesterase (rhBChE)
      complexed with a series of copolymers of poly-l-lysine (PLL) with grafted
      (polyethylene) glycol (PEG) (i.e., PLL-g-PEG) showed reduced catalytic activity
      but relatively similar concentration-dependent inactivation of the
      organophosphorus inhibitor paraoxon. Herein, we compared the kinetics of
      catalysis (using butyrylthiocholine as the substrate) and inhibition (using four
      different inhibitors) of free and copolymer-complexed rhBChE. Using scanning
      electron microscopy, polyionic complexes of rhBChE with three different PLL-g-PEG
      copolymers (based on PLL size) appeared as spheroid-shaped particles with
      relatively similar particle sizes (median diameter = 35 nm). Relatively similar
      particle sizes were also noted using dynamic light scattering (mean = 26-35 nm).
      The three copolymer-complexed enzymes exhibited reduced kcat (30-33% reduction),
      but no significant changes in Km. Inhibitory potency (as reflected by the
      bimolecular rate constant, ki) was similar among the free and copolymer-complexed
      enzymes when paraoxon was the inhibitor, whereas statistically significant
      reductions in ki (16-60%) were noted with the other inhibitors. Sensitivity to
      inactivation by proteases and heat was also compared. Copolymer-complexed enzymes
      showed lesser time-dependent inactivation by the proteases trypsin and pronase
      and by heat compared to the free enzyme. Understanding the unique properties of
      PLL-g-PEG-BChE complexes may lead to enhanced approaches for use of BChE and
      other protein bioscavengers.

PMID- 28756152
TI  - Ophthalmologic Features of Progeria.
AB  - PURPOSE: To establish the natural history of ophthalmic characteristics in
      Progeria patients and to determine incidence of ocular manifestations. DESIGN:
      Retrospective case series of patients with Progeria who were seen between 2007
      and 2016. METHODS: Setting: Tertiary-care academic center. PATIENT POPULATION:
      Fourteen patients (28 eyes) with Hutchinson-Gilford Progeria syndrome were
      included for statistical analysis from a total of 84 patients who have been
      enrolled in clinical trials for Progeria at Boston Children's Hospital. Clinical
      treatment trial patients who were not seen at the Department of Ophthalmology at
      our hospital, but for whom we had detailed clinical ophthalmologic records, were
      also included. This essentially represents an estimated 20% of the world's known
      patients with Progeria. Interventions or Observation Procedures: Complete
      ophthalmic examination. MAIN OUTCOME MEASURES: Visual acuity, stereoacuity,
      refraction, clinical findings of slit-lamp and dilated fundus examinations.
      RESULTS: Ophthalmic manifestations noted were hyperopia and signs of ocular
      surface disease owing to nocturnal lagophthalmos and exposure keratopathy.
      Additional ophthalmic manifestations included reduced brow hair, madarosis, and
      reduced accommodation. Most patients had relatively good acuity; however,
      advanced ophthalmic disease was associated with reduced acuity. CONCLUSIONS:
      Children with Progeria are at risk for serious ophthalmic complications owing to
      ocular surface disease. Children with Progeria should have an ophthalmic
      evaluation at the time of diagnosis and at least yearly after that. Aggressive
      ocular surface lubrication is recommended, including the use of tape tarsorrhaphy
      at night.

PMID- 28756153
TI  - Hybrid pharmacophore approach for bio-relevant di-imines based homobimetallic
      complexes incorporating functionalized dicarboxylates as co-ligands: Synthesis,
      spectral and structural activity dependent biological insights (in-vitro DNA and
      HSA binding, antioxidant and cytotoxicity).
AB  - Synthesis of bio-efficient homobimetallic complexes, [Cu2(L1)2(dipic)](NO3)2.3H2O
      (1), [Zn2(L1)2(dipic)](NO3)2.4H2O (2), [Cu2(L2)2(oxa)](NO3)2.4H2O (3) and
      [Zn2(L2)2(oxa)] (NO3)2.5H2O (4) was carried out using Schiff bases [(N1E,N2E)
      N1,N2-bis(5-chlorothiophen-2-ylmethylene)-4-chlorobenzene-1,2-diamine; L1] and
      [(N1E,N2E)-N1,N2-bis(5-chlorofuran-2-ylmethylene)-4-chlorobenzene-1,2-diamine;
      L2] as main ligands and dicarboxylate moieties of 2,6-pyridine dicarboxylic acid
      (H2-dipic) and oxalic acid (H2-oxa) as co-ligands, respectively in order to
      apprehend their structure activity relationships on the basis of pharmacophore
      hybrid approach. The stoichiometry, geometry, thermal stability, morphology and
      crystallite size of the compounds were inferred by analytical, spectral (FT-IR,
      1H NMR and 13C NMR and Mass), thermal (TGA/DTA), SEM and XRD studies. In-vitro
      DNA and HSA binding profiles of complexes were analysed by different biophysical
      measurements. The absorption study divulged that the observed alterations in the
      physico-chemical properties of complexes upon binding with DNA connoted their
      intercalative binding mode while fluorescence quenching mechanism was quantified
      by using Stern Volmer constant (KSV); 1.73*104 (1), 1.47*104 (2), 5.65*103 (3)
      and 3.60*103M-1 (4) which discerned that hybrid pharmacophore active metal
      complexes (1 and 2) exhibited efficient quenching effect with Ct-DNA in
      comparison to complexes (3 and 4) due to greater planarity and extent of
      conjugation (pi-pi interactions). The intercalative binding mode of complexes is
      further supported by competitive displacement assay by using fluorogenic dyes
      (EtBr and Hoechst 33258). The results of HSA fluorescence study divulged static
      quenching of the complexes (1-4) with KSV values of 7.24*104 (1), 6.03*104 (2),
      5.06*104 (3) and 2.85*104 (4) while Kb values; 1.16*105 (1), 2.01*104 (2),
      5.84*103 (3) and 8.60*102 (4) suggested them potent avid binder of HSA.
      Additionally, comparative estimation of scavenging properties using DPPH,
      superoxide(O2.-), hydroxyl (OH-) and ABTS method and in-vitro cytotoxicity
      against different cell lines (MCF-7, HeLa and Hep G2) brought out distinct
      biopotency of complexes due to diverse structural features and chelation effect.

PMID- 28756154
TI  - Photodynamic therapy for actinic keratosis: Is the European consensus protocol
      for daylight PDT superior to conventional protocol for Aktilite CL 128 PDT?
AB  - BACKGROUND: Topical photodynamic therapy (PDT) is an established treatment
      modality for various dermato-oncologic conditions. In Europe, initially requiring
      irradiation with red light, PDT of actinic keratosis (AK) can now also be carried
      out with exposure to daylight that has been clinically proven to be as effective
      as and less painful than red light. OBJECTIVES: In this paper, we propose a
      comparison between the conventional protocol for Aktilite CL 128 (red light
      source) PDT and the European consensus protocol for daylight PDT - with the
      exposure is assumed to be performed during either a clear sunny day or an
      overcast day - in the treatment of AK with methyl aminolevulinate through a
      mathematical modeling. METHOD: This already published modeling that is based on
      an iterative procedure alternating determination of the local fluence rate and
      updating of the local optical properties enables to estimate the local damage
      induced by the therapy. RESULTS: The European consensus protocol for daylight PDT
      during a sunny day and an overcast day provides, on average, 6.50 and 1.79 times
      higher PDT local damages at the end of the treatment than those obtained using
      the conventional protocol for Aktilite CL 128 PDT, respectively. CONCLUSIONS:
      Results analysis shows that, even performed during an overcast day, the European
      consensus protocol for daylight PDT leads to higher PDT local damages than the
      efficient conventional protocol for Aktilite CL 128.

PMID- 28756155
TI  - Formation of Matricaria chamomilla extract-incorporated Ag nanoparticles and size
      dependent enhanced antimicrobial property.
AB  - Various concentrations of Matricaria chamomilla (M. chamomilla) flower extract
      was used for biosynthesis of Ag NPs with different sizes, 70+/-5 (Ag NP-1), 52+/
      5 (Ag NP-1) and 37+/-4nm (Ag NP-3), and size-specific antimicrobial activity of
      them was evaluated towards Gram+ Staphylococcus aureus (S. aureus), Gram-
      Escherichia coli (E. coli) bacteria and Candida fungus albicans (C. albicans). We
      also examine the formation of Ag NPs as a function of the plant extract volume,
      Ag ion concentration (Ag+) and reaction time. M. chamomilla flower extract at
      100ppm shows mild inhibitory effect by inhibiting growth of all target pathogens.
      The extract mediated Ag NPs even at low concentration (6.25ppm) caused reductions
      in cell densities of the pathogens. The potential reasons for the highly
      effective inhibitory activity of the extract mediated Ag NPs are: (1) synergistic
      effects due to combination of M. chamomile extract and Ag NP because Ag NP is an
      effective germicidal and M. chamomile plant itself shows mild inhibitory
      property, (2) high localized concentration of M. chamomile extract due to nano
      scale entrapment of it on surface of Ag NP and (3) size-specific antibacterial
      efficacy of Ag NP because small size increases the active surface area of Ag NP,
      which reacting bacterial cells and increases number of extract molecules anchored
      on the surface of Ag NP.

PMID- 28756156
TI  - Antimicrobial photodynamic therapy by means of porphycene photosensitizers.
AB  - Antimicrobial photodynamic therapy (APDT) is one of the promising tools for
      bacteria inactivation, which can be considered as an alternative to the common
      ways of treatment in the era of growing resistance to antibiotics. Presently
      applied phototherapeutic agents are often based on porphyrins. Porphycenes,
      isomers of porphyrin, exhibit even better spectral and photophysical properties
      regarding PDT and have therefore been proposed as photosensitizers in such
      applications as anticancer and antimicrobial PDT. We compare three different
      porphycenes in the study of photodestruction of commonly occurring bacteria:
      Enteroccocus faecalis, Staphylococcus aureus and Staphylococcus epidermidis.
      Special interest is drawn to the parent, unsubstituted porphycene, a compound
      which was not tested before in terms of its photosensitizing activity in the
      biological systems. The results show that two out of three investigated
      compounds, the parent porphycene and its quadruply substituted derivative,
      2,7,12,17-tetrakis(beta-methoxyethyl) exhibit very good ability of bacteria
      eradication and fulfill the criteria that are commonly required from the APDT
      photosensitizers. In contrast, 2,7,12,17-tetra-t-butylporphycene, of which the
      spectral and photophysical characteristics are very similar to those of the
      parent compound, is not photoactive. This is explained by its inability to
      penetrate into the bacteria cell. These results demonstrate extreme sensitivity
      of the photodestruction efficiency to minor structural variations in the
      photosensitizer.

PMID- 28756157
TI  - Degradation of anthropogenic pollutant and organic dyes by biosynthesized silver
      nano-catalyst from Cicer arietinum leaves.
AB  - The work represents the potent catalytic activity of silver nanoparticles
      synthesized from Cicer arietinum (chickpea) leaf extract (CAL-AgNPs). Here,
      silver nano-catalysts were used against the anthropogenic pollutants mainly
      involving nitro-amines and azo dyes. These pollutants are extremely harmful to
      our environment and causes severe health issues. The CAL-AgNPs have the potential
      to degrade harmful toxins and their by-products, thereby decreasing the
      pollutants from the environment. The green synthesis of nano-catalyst includes a
      simple, cost effective and eco-friendly method using the leaf extract from the
      plant. A systematic study was conducted, including synthesis, optimization and
      characterization of the silver particles. The AgNPs were further assessed through
      DLS and TEM for size and morphological evaluation. The obtained particles have
      shown spherical morphology with the size range of 88.8nm. Further, FTIR were
      performed for compositional and functional group analysis of the particles. The
      antibacterial efficiency was also evaluated against E. coli and P. aeruginosa.
      For their catalytic evaluation, CAL-AgNPs were assessed for 4-nitrophenol,
      methylene blue and congo red. The results obtained through catalytic evaluation
      suggested that the CAL-AgNPs could be helpful to surmount the environmental
      pollution in a very effective manner.

PMID- 28756158
TI  - Bioluminescent and biochemical properties of Cys-free Ca2+-regulated
      photoproteins obelin and aequorin.
AB  - Bioluminescence of a variety of marine coelenterates is determined by Ca2+
      regulated photoproteins. A strong interest in these proteins is for their wide
      analytical potential as intracellular calcium indicators and labels for in vitro
      binding assays. The presently known hydromedusan Ca2+-regulated photoproteins
      contain three (aequorin and clytin) or five (obelin and mitrocomin) cysteine
      residues with one of them strictly conserved. We have constructed Cys-free
      aequorin and obelin by substitution of all cysteines to serine residues. Such
      mutants should be of interest for researchers by the possibility to avoid the
      incubation with dithiothreitol (or beta-mercaptoethanol) required for producing
      an active photoprotein that is important for some prospective analytical assays
      in which the photoprotein is genetically fused with a target protein sensitive to
      the reducing agents. Cys-free mutants were expressed in Escherichia coli,
      purified, and characterized regarding the efficiency of photoprotein complex
      formation, functional activity, and conformational stability. The replacement of
      cysteine residues has been demonstrated to affect different properties of
      aequorin and obelin. Cys-free aequorin displays a two-fold lower specific
      bioluminescence activity but preserves similar activation properties and light
      emission kinetics compared to the wild-type aequorin. In contrast, Cys-free
      obelin retains only ~10% of the bioluminescence activity of wild-type obelin as
      well as binding coelenterazine and forming active photoprotein much less
      effectively. In addition, the substitution of Cys residues drastically changes
      the bioluminescence kinetics of obelin completely eliminating a "fast" component
      from the light signal decay curve. At the same time, the replacement of Cys
      residues increases conformational flexibility of both aequorin and obelin
      molecules, but again, the effect is more prominent in the case of obelin. The
      values of thermal midpoints of unfolding (Tm) were determined to be 53.3+/-0.2
      and 44.6+/-0.4 degrees C for aequorin and Cys-free aequorin, and 49.1+/-0.1 and
      28.8+/-0.3 degrees C for obelin and Cys-free obelin, respectively. Thus, so far
      only Cys-free aequorin is suitable as a partner for fusing with a tag sensitive
      to reducing agents since the aequorin mutant preserves almost 50% of the
      bioluminescent activity and can be produced with a substantial yield.

PMID- 28756159
TI  - Automatic identification of high impact articles in PubMed to support clinical
      decision making.
AB  - OBJECTIVES: The practice of evidence-based medicine involves integrating the
      latest best available evidence into patient care decisions. Yet, critical
      barriers exist for clinicians' retrieval of evidence that is relevant for a
      particular patient from primary sources such as randomized controlled trials and
      meta-analyses. To help address those barriers, we investigated machine learning
      algorithms that find clinical studies with high clinical impact from PubMed(r).
      METHODS: Our machine learning algorithms use a variety of features including
      bibliometric features (e.g., citation count), social media attention, journal
      impact factors, and citation metadata. The algorithms were developed and
      evaluated with a gold standard composed of 502 high impact clinical studies that
      are referenced in 11 clinical evidence-based guidelines on the treatment of
      various diseases. We tested the following hypotheses: (1) our high impact
      classifier outperforms a state-of-the-art classifier based on citation metadata
      and citation terms, and PubMed's(r) relevance sort algorithm; and (2) the
      performance of our high impact classifier does not decrease significantly after
      removing proprietary features such as citation count. RESULTS: The mean top 20
      precision of our high impact classifier was 34% versus 11% for the state-of-the
      art classifier and 4% for PubMed's(r) relevance sort (p=0.009); and the
      performance of our high impact classifier did not decrease significantly after
      removing proprietary features (mean top 20 precision=34% vs. 36%; p=0.085).
      CONCLUSION: The high impact classifier, using features such as bibliometrics,
      social media attention and MEDLINE(r) metadata, outperformed previous approaches
      and is a promising alternative to identifying high impact studies for clinical
      decision support.

PMID- 28756160
TI  - A cascaded approach for Chinese clinical text de-identification with less
      annotation effort.
AB  - With rapid adoption of Electronic Health Records (EHR) in China, an increasing
      amount of clinical data has been available to support clinical research. Clinical
      data secondary use usually requires de-identification of personal information to
      protect patient privacy. Since manually de-identification of free clinical text
      requires significant amount of human work, developing an automated de
      identification system is necessary. While there are many de-identification
      systems available for English clinical text, designing a de-identification system
      for Chinese clinical text faces many challenges such as unavailability of
      necessary lexical resources and sparsity of patient health information (PHI) in
      Chinese clinical text. In this paper, we designed a de-identification pipeline
      taking advantage of both rule-based and machine learning techniques. Our method,
      in particular, can effectively construct a data set with dense PHI information,
      which saves annotation time significantly for subsequent supervised learning. We
      experiment on a dataset of 3000 heterogeneous clinical documents to evaluate the
      annotation cost and the de-identification performance. Our approach can increase
      the efficiency of the annotation effort by over 60% while reaching performance as
      high as over 90% measured by F score. We demonstrate that combing rule-based and
      machine learning is an effective way to reduce the annotation cost and achieve
      high performance in Chinese clinical text de-identification task.

PMID- 28756161
TI  - ctPath: Demixing pathway crosstalk effect from transcriptomics data for
      differential pathway identification.
AB  - Identifying differentially expressed pathways (DEPs) plays important roles in
      understanding tumor etiology and promoting clinical treatment of cancer or other
      diseases. By assuming gene expression to be a sparse non-negative linear
      combination of hidden pathway signals, we propose a pathway crosstalk-based
      transcriptomics data analysis method (ctPath) for identifying differentially
      expressed pathways. Biologically, pathways of different functions work in concert
      at the systematic level. The proposed method interrogates the crosstalks between
      pathways and discovers hidden pathway signals by mapping high-dimensional
      transcriptomics data into a low-dimensional pathway space. The resulted pathway
      signals reflect the activity level of pathways after removing pathway crosstalk
      effect and allow a robust identification of DEPs from inherently complex and
      noisy transcriptomics data. CtPath can also correct incomplete and inaccurate
      pathway annotations which frequently occur in public repositories. Experimental
      results on both simulation data and real-world cancer data demonstrate the
      superior performance of ctPath over other popular approaches. R code for ctPath
      is available for non-commercial use at the URL
      http://micblab.iim.ac.cn/Download/.

PMID- 28756162
TI  - A single spike deteriorates synaptic conductance estimation.
AB  - We investigated the estimation accuracy of synaptic conductances by analyzing
      simulated voltage traces generated by a Hodgkin-Huxley type model. We show that
      even a single spike substantially deteriorates the estimation. We also
      demonstrate that two approaches, namely, negative current injection and spike
      removal, can ameliorate this deterioration.

PMID- 28756163
TI  - Information reduction in a reverberatory neuronal network through convergence to
      complex oscillatory firing patterns.
AB  - Dynamics of a reverberating neural net is studied by means of computer
      simulation. The net, which is composed of 9 leaky integrate-and-fire (LIF)
      neurons arranged in a square lattice, is fully connected with interneuronal
      communication delay proportional to the corresponding distance. The network is
      initially stimulated with different stimuli and then goes freely. For each
      stimulus, in the course of free evolution, activity either dies out completely or
      the network converges to a periodic trajectory, which may be different for
      different stimuli. The latter is observed for a set of 285290 initial stimuli
      which constitutes 83% of all stimuli applied. After applying each stimulus from
      the set, 102 different periodic end-states are found. The conclusion is made,
      after analyzing the trajectories, that neuronal firing is the necessary
      prerequisite for merging different trajectories into a single one, which
      eventually transforms into a periodic regime. Observed phenomena of self
      organization in the time domain are discussed as a possible model for processes
      taking place during perception. The repetitive firing in the periodic regimes
      could underpin memory formation.

PMID- 28756164
TI  - Age differences in optimism bias are mediated by reliance on intuition and
      religiosity.
AB  - The relationships among age, optimism bias, religiosity, creationist beliefs, and
      reliance on intuition were examined in a sample of 211 high school students
      (Mage=16.54years). Optimism bias was defined as the difference between
      predictions for positive and negative live events (e.g., divorce) for the self
      and age peers. Results indicated that older adolescents displayed less optimism
      bias, were less religious, believed less in creationism, and relied on intuition
      less than younger adolescents. Furthermore, the association between age and
      optimism bias was mediated by religiosity and reliance on intuition but not by
      creationist beliefs. These findings are considered from a dual-process theoretic
      perspective that emphasizes age increases in metacognitive abilities and
      epistemological beliefs and age declines in impulsive judgments. Research
      directed toward examining alternative explanations of the association among
      religiosity, age, and optimism bias is recommended.

PMID- 28756165
TI  - Pathways to care among persons with dementia: Study from a tertiary care center.
AB  - The prevalence of dementia is increasing rapidly, specifically in low and middle
      income countries (LAMIC) due to demographic aging. Help seeking is delayed and
      usually sought at an advanced stage of illness and many are yet to receive a
      formal diagnosis. We interviewed 35 caregivers of persons with Dementia (as per
      ICD-10) using a semi-structured questionnaire, the Short Explanatory Model
      Interview (SEMI). We explored the pathways taken by caregivers of people with
      dementia en route to a tertiary care centre and the interactions they had with
      different health care providers. Qualitative data analysis was done using
      ATLAS.ti. We identified three major pathways: I) The Neuropsychiatric pathway II)
      The General Practitioner pathway and III) The Non-cohesive pathway. In general,
      the caregivers were poorly informed about the illness details such as diagnosis,
      course and outcome. Neurologists communicated the diagnosis of 'Dementia' more
      frequently. When information was made available, the caregivers were satisfied
      with proper information about illness and with at least, partial improvement of
      symptoms. There is a need for increasing the awareness of dementia in community
      at large. Health services and systems that address this important public health
      problem need strengthening. Sensitization and training of primary care physician
      and staff to identify dementia at an early stage are the need of the hour.

PMID- 28756166
TI  - Transformational Changes in Health Status: A Qualitative Exploration of Healing
      Moments.
AB  - BACKGROUND AND AIMS: Dramatic self-change is a familiar concept within religious
      experience and is recognized within psychotherapy and some fields of nursing.
      However, it has been given limited consideration in wider health research,
      including healing research. We sought to explore the phenomenon of "healing
      moments". METHODS: Alternative medicine practitioners attending a continuing
      professional development course for healers within the UK's Holistic Health Show
      were shown a 10min video clip showing two of the authors discussing healing
      moments. Sixty-nine (69) of the practitioners then provided "short stories"
      outlining their own experiences of such moments. Both the video and the short
      stories were analyzed qualitatively using a thematic approach. We sought to
      evaluate holistic practitioners' perceptions of the concept of healing moments.
      RESULTS: The concept of healing moments was widely accepted by the 69
      participants. An overarching theme of transformational change described personal
      shifts that ranged from the sudden and quasimiraculous to transient but much
      needed improvements in health and wellbeing. Three subordinate themes of
      connectivity, quiescence and control were identified. Connectivity described
      intense connections, experienced through touch, empathy and love, which could
      provide reciprocal benefits for healers as well as clients. Quiescence captured
      the quiet, calm atmosphere that pervaded many healing episodes. The contrasting
      aspects of control encompassed healers relinquishing control to channel healing,
      and clients seizing control to become empowered in their own healing process.
      CONCLUSION: Healing moments are a recognized and distinct concept within healing,
      although they remain under-explored in the literature. Our findings suggest that
      such experiences are common among alternative medicine practitioners. The
      concepts we uncovered can inform future research.

PMID- 28756167
TI  - A multimodal infection control concept in a burn intensive care unit - lessons
      learnt from a meticillin-resistant Staphylococcus aureus outbreak.
AB  - BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) is a frequently
      encountered pathogen in burn units. Burn patients are especially susceptible to
      MRSA acquisition and MRSA spread may cause outbreaks in burn units. AIM: To
      report the characteristics and successful control of an MRSA outbreak and to
      demonstrate a multimodal infection control concept. METHODS: In addition to a pre
      existing infection control concept, several control measures were implemented
      including weekly prevalence screenings for MRSA, reinforcement of disinfection,
      restriction of admissions, and short-term unit closure. Epidemiologic
      investigation and environmental examinations were performed. The outbreak
      isolates were analysed by pulsed-field gel electrophoresis and spa-typing. A
      PubMed search was conducted, focusing on MRSA outbreaks in burn units. FINDINGS:
      This outbreak of hospital-acquired MRSA affected eight patients during a seven
      month period, yielding an attack rate of 8%. Epidemiologic and environmental
      examinations suggested patient-to-patient transmission, which was confirmed by
      molecular analysis of bacterial isolates revealing a monoclonal pattern. In
      accordance with findings from other outbreaks in burn units, the implemented
      measures including patient screening and temporary unit closure resulted in
      successful control of the outbreak. CONCLUSION: A comprehensive concept is
      required to control the spread of all multidrug-resistant micro-organisms
      including MRSA on a burn unit. Where patients colonized or infected with MRSA
      appear to be the main reservoir, transfer of these patients to other units, or
      temporary closure of the unit, accompanied by intensive cleaning are very
      effective measures to stop transmission events.

PMID- 28756168
TI  - Difficulty with decontaminating dummies (pacifiers, soothers or comforters) for
      infants in hospital.

PMID- 28756169
TI  - Public health and healthcare-associated risk of electric, warm-water bidet
      toilets.
AB  - BACKGROUND: In recent years, installation of bidet toilets within hospitals in
      Japan has raised concerns regarding potential for cross-contamination by
      antimicrobial-resistant bacteria from patients who are hospitalized over an
      extended period. AIM: To investigate the distribution of antimicrobial-resistant
      bacteria recovered from bidet toilets at a university-affiliated hospital in
      Japan. METHODS: All 292 electric bidet toilets at a university hospital were
      sampled for contamination. Swabs for culture were used to sample water-jet
      nozzles and toilet seats. FINDINGS: Of the 292 toilet seats sampled, warm-water
      nozzles of 254 (86.9%) were found to be contaminated by one or more of the
      following organisms: Staphylococcus aureus, Streptococcus spp., Enterococcus
      spp., Enterobacteriaceae and non-Enterobacteriaceae Gram-negative bacteria. S.
      aureus was recovered from one water-jet nozzle and nine toilet seats; of these,
      meticillin-resistant S. aureus was recovered from the water-jet nozzle and from
      one toilet seat. Both the water-jet nozzle and seat of the same toilet were
      contaminated with a CTX-M-9 group extended-spectrum beta-lactamase-producing
      Escherichia coli. Of the Gram-negative isolates recovered from samples, the
      organism with the highest frequency of isolation was Stenotrophomonas
      maltophilia, which was recovered from 39 bidet toilets. CONCLUSION: Warm-water
      nozzles of bidet toilets are contaminated with a wide range of bacteria, making
      them a potential vehicle for cross-infection. In the hospital setting, shared use
      of bidet toilets must consider the clinical background of patients. Based on
      these findings, these devices must be part of the risk management programme, and
      steps should be included for monitoring and disinfection.

PMID- 28756170
TI  - Confirmation of metabolites of the neuroleptic drug prothipendyl using human
      liver microsomes, specific CYP enzymes and authentic forensic samples-Benefit for
      routine drug testing.
AB  - Metabolism of the tricyclic azaphenothiazine neuroleptic drug prothipendyl was
      investigated with in vitro studies using human liver microsomes but also specific
      isoforms of cytochrome P450 (CYP) enzymes. Identification and analysis of
      metabolites was done by liquid chromatography (LC) coupled with quadrupole time
      of flight mass spectrometry (LC-QTOF-MS) as well as triple quadrupole mass
      spectrometry (LC-QQQ-MS). Results of the herein presented study revealed the
      proof of various demethylated and oxidized metabolites (-CH2, -C2H4, four
      derivatives of prothipendyl +O and three derivatives of prothipendyl -CH2+O).
      Metabolic reactions of prothipendyl were mainly catalyzed by CYP enzymes CYP1A2,
      CYP2D6, CYP2C19 and CYP3A4. N-demethyl-prothipendyl was predominantly formed by
      isoforms CYP2C19 and CYP1A2, while particularly the CYP isoenzyme 3A4 was
      responsible for the formation of prothipendyl sulfoxide. To confirm the formation
      of previously identified metabolites in vivo, cardiac blood samples that were
      tested positive for prothipendyl during routine drug testing and serum and urine
      samples, collected after a voluntary intake of prothipendyl, were analyzed by LC
      QQQ-MS. All metabolites of prothipendyl were proven in these authentic specimens.
      Neither in serum samples nor in urine samples, a prolonged detectability of
      metabolites in comparison to prothipendyl could be demonstrated.

PMID- 28756171
TI  - Quantification of 16 beta-lactams in chicken muscle by QuEChERS extraction and
      UPLC-Q-Orbitrap-MS with parallel reaction monitoring.
AB  - A method is described for the analysis of 16 beta-lactams in chicken muscle by
      UPLC-quadrupole(Q)-Orbitrap-MS with parallel reaction monitoring (PRM). QuEChERS
      approach includes clean-up step by sorbent of primary-secondary amine (PSA) and
      C18 was adopted for sample preparation. Q-Orbitrap with PRM showed high
      sensitivity with limits of detection (LODs) ranged from 0.01MUgkg-1 to 0.35MUgkg
      1. The method was further validated by intra- and inter-day test with spiking
      levels less than MRLs (maximum residue limits, the European Union). Recovery (83
      112%) and precision values (RSDs <15%) for all studied analytes were obtained.
      The result indicates that UPLC-Q-Orbitrap coupled with QuEChERS preparation can
      serve as a routine quantification method for beta-lactam residues in chicken
      muscles.

PMID- 28756172
TI  - Characterization of co-existing colloidal structures in fasted state simulated
      fluids FaSSIF: A comparative study using AF4/MALLS, DLS and DOSY.

PMID- 28756173
TI  - Characterization of impurities in sodium cromoglycate drug substance and eye
      drops using LC-ESI-ion trap MS and LC-ESI-QTOF MS.
AB  - As requested by regulatory authorities, impurity profiling is an important issue
      of quality control. In this work, a simple and sensitive liquid chromatographic
      (LC) method compatible with mass spectrometry (MS) was developed to study related
      substances and degradation products in sodium cromoglycate drug substance and eye
      drops. The method used a Sunfire column (4.6mm*150mm, 3.5MUm). Mobile phase A
      consisted of 10mM ammonium formate and mobile phase B was acetonitrile. Linear
      gradient elution with a post-run time of 8min was performed as follows: 0-30min,
      3% B to 50% B; 30-35min, 50% B. The flow rate was set at 1.0mL/min. Degradation
      experiments were performed to check the stability indicating properties of the
      developed method. Based on MSn spectral data and exact mass measurements, the
      chemical structures of 2 unknown impurities and 6 unknown degradation products
      were characterized, including impurity C listed in the European Pharmacopoeia as
      unknown structure. In addition, a plausible mechanism for the formation of the
      degradation products was also proposed.

PMID- 28756174
TI  - The potent anti-cancer activity of Dioclea lasiocarpa lectin.
AB  - The lectin DLasiL was isolated from seeds of the Dioclea lasiocarpa collected
      from the northeast coast of Brazil and characterized for the first time by mass
      spectrometry, DNA sequencing, inductively coupled plasma-mass spectrometry,
      electron paramagnetic resonance, and fluorescence spectroscopy. The structure of
      DLasiL lectin obtained by homology modelling suggested strong conservation of the
      dinuclear Ca/Mn and sugar-binding sites, and dependence of the solvent
      accessibility of tryptophan-88 on the oligomerisation state of the protein.
      DLasiL showed highly potent (low nanomolar) antiproliferative activity against
      several human carcinoma cell lines including A2780 (ovarian), A549 (lung), MCF-7
      (breast) and PC3 (prostate), and was as, or more, potent than the lectins ConBr
      (Canavalia brasiliensis), ConM (Canavalia maritima) and DSclerL (Dioclea
      sclerocarpa) against A2780 and PC3 cells. Interestingly, DLasiL lectin caused a
      G2/M arrest in A2780 cells after 24h exposure, activating caspase 9 and delaying
      the on-set of apoptosis. Confocal microscopy showed that fluorescently-labelled
      DLasiL localized around the nuclei of A2780 cells at lectin doses of 0.5-2* IC50
      and gave rise to enlarged nuclei and spreading of the cells at high doses. These
      data reveal the interesting antiproliferative activity of DLasiL lectin, and
      suggest that further investigations to explore the potential of DLasiL as a new
      anticancer agent are warranted.

PMID- 28756175
TI  - New copper(II) thiohydantoin complexes: Synthesis, characterization, and
      assessment of their interaction with bovine serum albumin and DNA.
AB  - New copper(II) complexes of 2-alkylthio-5-arylmethylene-4H-imidazolin-4-ones:
      (5Z)-2-(methylsulfanyl)-3-(prop-2-en-1-yl)-5-(pyridin-2-ylmethylidene)-3,5
      dihydro-4H-imidazol-4-one) (1a), (5Z,5'Z)-2,2'-(ethan-1,2
      diyldisulfanyldiyl)bis(5-(2-pyridilmethylen)-3-allyl-3,5-dihydo-4N-imidazole-4
      one) (2a) and (5Z,5'Z)-3,3'-hexan-1,6-diylbis[5-(2-pyridilmethylen)-2
      methylthiotetrahydro-4N-imidazole-4-one)] (3a) were synthesized as possible
      anticancer drugs. Their structures were characterized by 1H NMR spectroscopy,
      elemental analysis, and X-ray crystallography. The composition of the complexes
      were found for 1a (Cu:L=1:1), 2a (Cu:L=2:1), and 3a (Cu:L=2:1). The chelation
      constants were found by competitive complexation with ethylenediamine
      tetraacetate: 1a (6.7+/-0.6)*1015M-1, 2a=(4.9+/-0.4)*1019M-2, and 3a (5.7+/
      0.5)*1019M-2. Supramolecular binding with calf thymus DNA by competitive ethidium
      bromide quenching was made for complex 2a as the most promising anticancer model,
      the Stern-Volmer constants were found to be KSV=(8.0+/-0.4)*106M-1, Kq=(6.5+/
      0.4)*105M-1. The binding of the complex 2a to BSA was made by the Scatchard
      method, the value of the constant is Kb=(1.9+/-0.2)*106M-1.

PMID- 28756176
TI  - Infection-mediated autoimmune movement disorders.
AB  - Infectious diseases remain the most common cause of neurological disability in
      the world. A number of movement disorders can develop in adults and children in
      response to infections. These can occur in isolation or as part of a broader
      neurological illness, with movement abnormalities consequent to an encephalopathy
      or a broader brain dysfunction. While most infection-related movement disorders
      are direct consequences of an active infectious process affecting cerebral
      structures implied in the motor network, at times a delayed immune-mediated
      process in response to a previous infectious is responsible for the neurological
      dysfunction. This immunological response can occur as a consequence of a number
      of pathogens, and develop at variable times after the initial infection. The most
      common infection-mediated autoimmune movement disorders are chorea, which is
      especially common in children, and other hyperkinetic disorders, but Parkinsonism
      and other hypokinetic movement disorders may also occur.

PMID- 28756177
TI  - Dementia with Lewy Bodies and Parkinson Disease Dementia: It is the Same Disease!
AB  - INTRODUCTION: The question whether DLB and PDD are distinct disorders has been
      debated in several forums. The two disorders, once parkinsonism is present in
      DLB, cannot be distinguished on clinical or pathological grounds. The conundrum
      exists for those DLB patients who do not yet have parkinsonism, and raises the
      parallel with patients who have Rapid Eye Movement Behavior Disorder but have not
      yet manifested parkinsonian signs. METHODS: A literature review was summarized to
      justify classification as a single disorder. RESULTS: Most clinical observations
      and trials point to these disorders, once parkinsonism is present in DLB, are
      identical. CONCLUSION: This article notes the advantage to clinical research and
      treatment by considering these two syndromes as the same so that medications
      approved for PDD and for PD psychosis can be extended to DLB patients and that
      resources for PD research and support can be also used for DLB.

PMID- 28756178
TI  - Cricket spin bowling remains in its biomechanical infancy.

PMID- 28756179
TI  - A Breakthrough in Genetics and its Relevance to Prevention of Coronary Artery
      Disease in LMIC.
AB  - More than 60 genetic risk variants predisposing to coronary artery disease (CAD)
      have been confirmed. The genetic risk for CAD is related to the number of genetic
      risk variants present and can be expressed as a genetic risk score (GRS), by
      summing the product of the number of high-risk variants inherited by each
      individual times the log of the odds ratio. Studies show risk stratification for
      CAD, based on the GRS, is more discriminatory than conventional risk factors and
      predicts the response to statin therapy. A prospective trial showed individuals
      with high GRS had 91% greater risk of cardiac events, and individuals with a
      healthy lifestyle had 46% fewer cardiac events than an unfavorable lifestyle. GRS
      remains the same throughout one's lifetime because your deoxyribonucleic acid
      does not change. GRS, determined as early as birth from saliva, is inexpensive
      and could transform the prevention of CAD in low- and middle-income countries.

PMID- 28756180
TI  - Does novel P5'N-1 mutation in combination with G6PD Asahi in an Indian male
      contribute to Budd Chiari Syndrome?

PMID- 28756181
TI  - Effects of escitalopram and imipramine on cocaine reinforcement and drug-seeking
      behaviors in a rat model of depression.
AB  - Depression and substance cocaine abuse are disorders with a high frequency of
      comorbidity. In the present study, we combined bilateral olfactory bulbectomy
      (OBX), an animal model of depression, with intravenous cocaine self
      administration and extinction/reinstatement in rats to investigate the effects of
      two antidepressant drugs, escitalopram (ESC) and imipramine (IMI), with the goal
      of determining whether these drugs altered cocaine-induced reinforcement and
      seeking behaviors. Acute administration of IMI (2.5-30mg/kg) reduced the cocaine
      reinforcement in OBX and SHAM rats. Moreover, IMI effectively reduced the cocaine
      seeking behavior after the drug acute or repeated administration during
      extinction training in OBX rats and SHAM-operated controls. By contrast, acutely
      administered ESC (2.5-20mg/kg) did not alter cocaine reinforcement in OBX rats or
      SHAM-operated controls. The lack of ESC effects was also demonstrated during
      reinstatement tests to study drug-seeking behavior after ESC repeated daily
      treatment during extinction trials. However, acute treatment with ESC dose
      dependently decreased the cocaine-seeking behavior and relapse triggered by
      cocaine priming or drug-associated conditioned cues in both OBX and SHAM rats.
      These results indicate the cocaine anti-reinforcement and anti-seeking efficacy
      of the two antidepressant drugs studied here. However, the mechanisms for the IMI
      and ESC activity should be clarified in further studies.

PMID- 28756182
TI  - Technical aspects and recommendations for single-cell qPCR.
AB  - Single cells are basic physiological and biological units that can function
      individually as well as in groups in tissues and organs. It is central to
      identify, characterize and profile single cells at molecular level to be able to
      distinguish different kinds, to understand their functions and determine how they
      interact with each other. During the last decade several technologies for single
      cell profiling have been developed and used in various applications, revealing
      many novel findings. Quantitative PCR (qPCR) is one of the most developed methods
      for single-cell profiling that can be used to interrogate several analytes,
      including DNA, RNA and protein. Single-cell qPCR has the potential to become
      routine methodology but the technique is still challenging, as it involves
      several experimental steps and few molecules are handled. Here, we discuss
      technical aspects and provide recommendation for single-cell qPCR analysis. The
      workflow includes experimental design, sample preparation, single-cell
      collection, direct lysis, reverse transcription, preamplification, qPCR and data
      analysis. Detailed reporting and sharing of experimental details and data will
      promote further development and make validation studies possible. Efforts aiming
      to standardize single-cell qPCR open up means to move single-cell analysis from
      specialized research settings to standard research laboratories.

PMID- 28756183
TI  - Vitamin K2 supplementation and arterial stiffness among renal transplant
      recipients-a single-arm, single-center clinical trial.
AB  - Subclinical vitamin K deficiency is prevalent among renal transplant recipients
      and is associated with an increased risk of cardiovascular disease. However, the
      association between vitamin K supplementation and improvement of arterial
      stiffness has not been explored in the renal transplant population. The KING
      trial (vitamin K2 In reNal Graft) is a single-arm study that evaluated the
      association between the change in vitamin K status and indices of arterial
      stiffness following 8 weeks of menaquinone-7 (vitamin K2) supplementation (360
      MUg once daily) among renal transplant recipients (n = 60). Arterial stiffness
      was measured using carotid-femoral pulse wave velocity (cfPWV). Subclinical
      vitamin K deficiency was defined as plasma concentration of dephosphorylated
      uncarboxylated matrix Gla protein (dp-ucMGP) >500 pmol/L.At baseline, 53.3% of
      the study subjects had subclinical vitamin K deficiency. Supplementation was
      associated with a 14.2% reduction in mean cfPWV at 8 weeks (cfPWV pre-vitamin K2
      = 9.8 +/- 2.2 m/s vs. cfPWV post-vitamin K2 = 8.4 +/- 1.5 m/s; P < .001). Mean dp
      ucMGP concentrations were also significantly reduced by 55.1% following
      menaquinone-7 supplementation with a reduction in the prevalence of subclinical
      deficiency by 40% (P = .001). When controlled for age, durations of hemodialysis
      and transplantation, and the change in 24-hour mean arterial pressure, the
      improvement in arterial stiffness was independently associated with the reduction
      in dp-ucMGP concentration (P = .014).Among renal transplant recipients with
      stable graft function, vitamin K2 supplementation was associated with improvement
      in subclinical vitamin K deficiency and arterial stiffness. (Clinicaltrials.gov:
      NCT02517580).

PMID- 28756184
TI  - Development and validation of a new loop-mediated isothermal amplification for
      detection of pathogenic Leptospira species in clinical materials.
AB  - Leptospirosis, a global zoonotic disease, is often neglected but has a
      significant impact on human health. Here we reported a new loop mediated
      isothermal amplification (LAMP) assay targeting lipL32 gene of pathogenic
      Leptospira spp. Polymerase chain reaction (PCR), nested-PCR and real-time PCR
      assays were included in this study for the comparison of analytic and diagnostic
      sensitivity and specificity. LipL32 LAMP we designed enables detection of 10
      copies of L. interrogans and has a higher diagnostic sensitivity (91.67%) and
      specificity (100%) than other PCR-based methods. The high sensitivity,
      specificity and flexible reaction conditions of the lipL32 LAMP assay makes it
      feasible for resource-limited countries and on-site application.

PMID- 28756185
TI  - Behavioural, physiological and biochemical responses to aquatic hypoxia in the
      freshwater crayfish, Paranephrops zealandicus.
AB  - Hypoxia resulting from aquatic eutrophication threatens the population health of
      the New Zealand freshwater crayfish (koura), Paranephrops zealandicus. An
      integrated study, combining behavioural, physiological and biochemical
      approaches, was therefore conducted to characterise the tolerance of this species
      to hypoxia. When provided with a choice between water flows of high or low
      dissolved oxygen in short-term laboratory assays, crayfish did not preferentially
      inhabit waters of higher PO2. However, when an aerial refuge was provided and
      dissolved oxygen was progressively decreased, crayfish emersed at a PO2 of 0.56+/
      0.03kPa, suggesting a relatively high tolerance to hypoxia. Closed-box
      respirometry delineated a Pcrit, the point at which crayfish transition from
      oxyregulating to oxyconforming, of 6.0kPa. Simultaneous measurement of heart rate
      showed no changes across the PO2 range. In response to 6-h exposures to fixed
      dissolved oxygen levels (normoxia, 19.3kPa; moderate hypoxia, 3.5kPa; and severe
      hypoxia, 1.7kPa), P. zealandicus showed a haemolymph PO2 that declined with the
      magnitude of hypoxia, and while plasma pH declined in severe hypoxia, there were
      no changes in plasma PCO2. Plasma glucose concentrations fell, and plasma lactate
      increased in both hypoxic groups. There were no changes in tissue glucose or
      lactate concentrations. These data indicate that P. zealandicus is relatively
      tolerant of hypoxia, and possesses biochemical and physiological mechanisms that
      facilitate survival during short-term exposures to acute hypoxia. If hypoxia is
      severe and/or prolonged, then this species is capable of escaping to aerial
      refugia.

PMID- 28756186
TI  - Event-related potential response to auditory social stimuli, parent-reported
      social communicative deficits and autism risk in school-aged children with
      congenital visual impairment.
AB  - Communication with visual signals, like facial expression, is important in early
      social development, but the question if these signals are necessary for typical
      social development remains to be addressed. The potential impact on social
      development of being born with no or very low levels of vision is therefore of
      high theoretical and clinical interest. The current study investigated event
      related potential responses to basic social stimuli in a rare group of school
      aged children with congenital visual disorders of the anterior visual system
      (globe of the eye, retina, anterior optic nerve). Early-latency event-related
      potential responses showed no difference between the VI and control group,
      suggesting similar initial auditory processing. However, the mean amplitude over
      central and right frontal channels between 280 and 320ms was reduced in response
      to own-name stimuli, but not control stimuli, in children with VI suggesting
      differences in social processing. Children with VI also showed an increased rate
      of autistic-related behaviours, pragmatic language deficits, as well as peer
      relationship and emotional problems on standard parent questionnaires. These
      findings suggest that vision may be necessary for the typical development of
      social processing across modalities.

PMID- 28756187
TI  - Under (implicit) pressure: young Black and Latina women's perceptions of
      contraceptive care.
AB  - OBJECTIVE: To understand the ways in which young women of color experienced
      pressure from healthcare providers during contraceptive care, including the
      impact of these encounters on contraceptive decision making and reproductive
      autonomy. METHODS: Data were drawn from a qualitative study of contraceptive
      decision making, which included 38 young (age 18-24) Latina and Black women
      recruited using community-based and online strategies. We analyzed in-depth
      interview data from a subsample of 27 young women who described experiencing
      pressure from healthcare providers during contraceptive care. We conducted a
      thematic analysis of coded data using a cross-case analytic approach. RESULTS:
      Our analysis revealed that the pressure experienced by our participants was
      typically subtle and constrained reproductive autonomy to varying degrees. We
      termed this phenomenon implicit pressure owing to the under-the-surface nature of
      these experiences - that is, participants perceived an implied outcome regarding
      contraceptive use favored by their providers. Participants felt implicitly
      pressured when providers appeared to prefer certain methods based on imbalanced
      provision of information, tone of voice and affect, and minimization of or
      failure to describe potential side effects. Some participants accepted their
      providers' contraceptive suggestions as a way to end counseling encounters -
      methods they rapidly discontinued. Experiences of implicit pressure were
      longitudinally impactful, with some participants curtailing future healthcare
      access and contraceptive use because of negative clinical encounters.
      CONCLUSIONS: Practices that implicitly pressure women in contraceptive counseling
      can infringe upon reproductive autonomy and reinforce health inequities when they
      engender mistrust of healthcare, providers and contraception. IMPLICATIONS: This
      study underscores the importance of high-quality contraceptive care for young
      women of color. Adverse healthcare experiences during adolescence and young
      adulthood can negatively impact future health-seeking behavior, with important
      implications for health throughout the life course. Patient-centered approaches
      may positively affect patients' experiences while continuing to facilitate
      contraceptive discussions.

PMID- 28756188
TI  - Long-term outcomes of proximal row carpectomy: A series of 62 cases.
AB  - The aim of this study was to determine and analyze the functional and
      radiographic outcomes after proximal row carpectomy (PRC). We hypothesized that
      this surgery could restore wrist mobility and function in case of radiocarpal
      osteoarthritis or severe carpal trauma. Sixty-two patients who had undergone PRC
      were included in this study: 44 patients with wrist osteoarthritis (11 SNAC, 24
      SLAC, 3 Kienbock's disease, 6 other) and 18 patients with severe carpal trauma.
      Each patient underwent clinical (pain, range of motion, grip strength, functional
      scores) and radiographic evaluations. At the latest evaluation after a mean of
      11.8 years, 15 patients (24.2%) required revision total wrist arthrodesis surgery
      in a median of 22 months (range, 6-179) because of disabling pain and lack of
      strength. The failure was statistically correlated with being young and a manual
      laborer. The range of motion and strength of the operated wrist were 61.5% and
      70%, respectively, compared to the contralateral side. PRC remains a reliable
      procedure for treating wrist arthritis and severe carpal trauma. However, manual
      activity and being under 50years of age can lead to an early salvage procedure
      such as total arthrodesis of the wrist. In this subset of the population, another
      alternative must be considered.

PMID- 28756190
TI  - miR-34a/Bcl-2 signaling pathway contributes to age-related hearing loss by
      modulating hair cell apoptosis.
AB  - MicroRNAs, such as miR-34, have been reported to influence age-related diseases.
      In this study, we explored the role of the miR-34a/Bcl-2 signaling pathway in age
      related hearing loss (AHL). Using an AHL mouse model (C57BL/6), we found that the
      expression of miR-34a in the cochlea increased with age, whereas expression of
      Bcl-2 decreased. Increasing the amount of a miR-34a mimetic in a mouse auditory
      cell line (HEI-OC1) inhibited Bcl-2, leading to enhanced apoptosis; in contrast,
      miR-34a inhibition produced the opposite effect. Our results support a link
      between age-related cochlear hair cell apoptosis and miR-34a/Bcl-2 signaling. The
      latter may thus serve as a potential target for AHL therapy.

PMID- 28756189
TI  - Historical pitfalls and new directions in the neuroscience of emotion.
AB  - In this article, we offer a brief history summarizing the last century of
      neuroscientific study of emotion, highlighting dominant themes that run through
      various schools of thought. We then summarize the current state of the field,
      followed by six key points for scientific progress that are inspired by a multi
      level constructivist theory of emotion.

PMID- 28756191
TI  - Serotonin transporter immunoreactivity is modulated during development and after
      fluoxetine treatment in the rodent visual system.
AB  - The serotonin transporter (5-HTT) regulates serotonin homeostasis and has been
      used as a target for different drugs in depression treatment. Although the
      serotonergic system has received a lot of attention, little is known about the
      effects of these drugs over serotonin transporters. In this work, we investigated
      the expression pattern of 5-HTT during development of the visual system and the
      influence of fluoxetine on different signaling pathways. Our data showed that the
      expression of 5-HTT has a gradual increase from postnatal day 0 until 42 and
      decrease afterwards. Moreover, chronic fluoxetine treatment both in childhood and
      adolescence induces down regulation of 5-HTT expression and phosphorylation of
      ERK and AKT signaling pathways. Together these data suggest that the levels of 5
      HTT protein could be important for the development of the central nervous system
      and suggest that the ERK and AKT are involved in the molecular pathways of
      antidepressants drugs, acting in concert to improve serotonergic signaling.

PMID- 28756192
TI  - Deletion variant rs35153737 in TOR1A is associated with isolated dystonia in a
      Southwestern Chinese Population.
AB  - BACKGROUND: TOR1A plays a very important role in early-onset isolated dystonia.
      Studying the association between the common variants of this gene and dystonia
      can help us understand the connection between TOR1A mutations and this disease.
      METHODS: The TOR1A exon 5 was sequenced in 223 isolated dystonia patients and 210
      age-adjusted controls. Patients and controls all came from Southwest China.
      RESULTS: The following two common variants were found in the 3'-UTR of TOR1A:
      NM_000113.2:c.*414delG (rs35153737) and NM_000113.2:c.*824delG (rs3842225). The
      rs35153737 variant showed a statistically significant association with dystonia
      using the allele model (P=0.035) and the dominant genetic model (P=0.018);
      however, no association between rs3842225 and dystonia was found. CONCLUSION: Our
      study suggests that there is an association between rs35153737 and dystonia in a
      southwestern Chinese population, and it may be caused by high linkage
      disequilibrium between this deletion and potential pathogenic variants in TOR1A.

PMID- 28756193
TI  - A photoclickable peptide microarray platform for facile and rapid screening of 3
      D tissue microenvironments.
AB  - Microarrays are powerful experimental tools for high-throughput screening of
      cellular behavior in multivariate microenvironments. Here, we present a new,
      facile and rapid screening method for probing cellular behavior in 3D tissue
      microenvironments. This method utilizes a photoclickable peptide microarray
      platform developed using electrospun fibrous poly(ethylene glycol) hydrogels and
      microarray contact printing. We investigated the utility of this platform with
      five different peptide motifs and ten cell types including stem, terminally
      differentiated, cancer or immune cells that were from either primary origin or
      cell lines and from different species. We validated the capabilities of this
      platform to screen arrays consisting of multiple peptide motifs and
      concentrations for selectivity to cellular adhesion and morphology. Moreover,
      this platform is amenable to controlled spatial presentation of peptides. We show
      that by leveraging the differential attachment affinities for two cell types to
      two different peptides, this platform can also be used to investigate cell-cell
      interactions through miniature co-culture peptide arrays. Our fibrous peptide
      microarray platform enables high-throughput screening of 3D tissue
      microenvironments in a facile and rapid manner to investigate cell-matrix
      interactions and cell-cell signaling and to identify optimal tissue
      microenvironments for cell-based therapies.

PMID- 28756194
TI  - Red blood cell membrane-camouflaged melanin nanoparticles for enhanced
      photothermal therapy.
AB  - Photothermal therapy (PTT) has represented a promising noninvasive approach for
      cancer treatment in recent years. However, there still remain challenges in
      developing non-toxic and biodegradable biomaterials with high photothermal
      efficiency in vivo. Herein, we explored natural melanin nanoparticles extracted
      from living cuttlefish as effective photothermal agents and developed red blood
      cell (RBC) membrane-camouflaged melanin (Melanin@RBC) nanoparticles as a platform
      for in vivo antitumor PTT. The as-obtained natural melanin nanoparticles
      demonstrated strong absorption at NIR region, higher photothermal conversion
      efficiency (~40%) than synthesized melanin-like polydopamine nanoparticles
      (~29%), as well as favorable biocompatibility and biodegradability. It was shown
      that RBC membrane coating on melanin nanoparticles retained their excellent
      photothermal property, enhanced their blood retention and effectively improved
      their accumulation at tumor sites. With the guidance of their inherited
      photoacoustic imaging capability, optimal accumulation of Melanin@RBC at tumors
      was achieved around 4 h post intravenous injection. Upon irradiation by an 808-nm
      laser, the developed Melanin@RBC nanoparticles exhibited significantly higher PTT
      efficacy than that of bare melanin nanoparticles in A549 tumor-bearing mice.
      Given that both melanin nanoparticles and RBC membrane are native biomaterials,
      the developed Melanin@RBC platform could have great potential in clinics for
      anticancer PTT.

PMID- 28756195
TI  - Ozone treatment of polysaccharides from Arthrocnemum indicum: Physico-chemical
      characterization and antiproliferative activity.
AB  - The isolation, purification and ozone depolymerization of polysaccharides from
      Arthrocnemum indicum as well as the evaluation of their antiproliferative
      capacities were investigated. The ozone treatment for various reaction times (0,
      15, 30, 45 and 60min) was employed as degradation method in order to attain lower
      molecular weight product with stronger antiproliferative property. According to
      FTIR, 1H NMR and UV-vis analysis, the main chain of ozonolytic degraded
      polysaccharides could be preserved. The monosaccharide composition, which was
      determined via GC/MS analysis, showed that extracted polysaccharides were of type
      of arabinan-rich pectic polysaccharides. Macromolecular characteristics as well
      as intrinsic viscosity of the degraded polysaccharides were performed by size
      exclusion chromatography before and after ozone treatment. These experiments
      showed that intrinsic viscosity and molecular weight (Mn and Mw) of degraded
      samples decreased with increase in reaction time. Furthermore, preliminary
      antiproliferative tests indicated that degraded polysaccharide for 1h showed even
      better antiproliferative capacity.

PMID- 28756196
TI  - Inhibition of bacterial biofilms by carboxymethyl chitosan combined with silver,
      zinc and copper salts.
AB  - Investigation of the antimicrobial action of carboxymethyl chitosan (CMCh) is
      among the alternative approaches in the control of pathogenic microorganisms.
      This study aimed to screen the toxicity using the brine shrimp lethality assay
      and to investigate the inhibitory activity of carboxymethyl in isolation or in
      combination with silver nitrate, copper sulfate and zinc sulfate on biofilm
      formation by Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC
      12228, Kocuria rhizophila ATCC 9341, Pseudomonas aeruginosa ATCC 9027,
      Escherichia coli ATCC 25312, and Burkholderia cepacia ATCC 17759. The CMCh was
      obtained by reacting chitosan with monochloroacetic acid under alkaline
      conditions, and the occurrence of carboxymethylation was evidenced by FTIR and 1H
      NMR spectroscopy. The CMCh was combined with metallic salts (AgNO3, CuSO4.5H2O
      and ZnSO4) to perform the bioassays to screen the toxicity, to determine the
      minimum inhibitory concentration and the impact of sub-inhibitory concentrations
      against biofilm formation. Although CMCh did not show inhibitory activity against
      bacterial growth, it had an interesting level of inhibition of bacterial biofilm.
      The results suggest that sub-inhibitory concentrations of compounds were
      effective against biofilm formation.

PMID- 28756197
TI  - alpha-Glucosidase inhibitory effect of Potentilla astracanica and some
      isoflavones: Inhibition kinetics and mechanistic insights through in vitro and in
      silico studies.
AB  - alpha-Glucosidase enzyme inhibitors are clinically used for the treatment of Type
      2 diabetes mellitus. We tested alpha-glucosidase inhibitory effects of Potentilla
      astracanica Jacq. extracts (1, 2), two compounds isolated from these extracts,
      prunetin 5-O-beta-glucopyranoside (3) and genistein 5-O-beta-glucopyranoside (4),
      and their aglycon forms (5 and 6). All the tested materials possessed remarkable
      alpha-glucosidase inhibitor activity compared to the positive control, acarbose.
      Genistein (6) showed the highest activity with an IC50 value of 1.47 (+/-0.11)
      MUg/ml. An enzyme kinetics analysis revealed that 3 and 6 were uncompetitive, 5
      was noncompetitive, and 4 was competitive inhibitors. Using molecular modeling
      techniques we tried to provide insight into molecular mechanisms of their
      activity and how allosteric binding of 6 affected binding interactions between
      the agonist (maltose) and the enzyme.

PMID- 28756198
TI  - High level expression of beta-mannanase (RmMan5A) in Pichia pastoris for
      partially hydrolyzed guar gum production.
AB  - Partially hydrolyzed guar gum (PHGG), an important supplemental dietary fiber,
      has been used as food ingredient in many industries. In this study, a novel beta
      mannanase gene (RmMan5A) from Rhizomucor miehei was successfully expressed in
      Pichia pastoris and subjected for PHGG production. Enzyme activity of
      fermentation supernatant reached 85,200UmL-1 after 168h high cell density
      fermentation. The purified RmMan5A exhibited the highest enzyme activity at pH
      7.0 and 65 degrees C. RmMan5A was then employed for guar gum hydrolysis and PHGG
      obtained demonstrated a weight-average molecular weight (Mw) of 2.5*104Da. Total
      dietary fiber accounted 90.6% of PHGG and 24.9% (w/w) of PHGG were identified as
      manno-oligosaccharides with degree of polymerization<7. PHGG was further
      fractionated (F1-F4) by gradual ethanol precipitation. PHGG F1 with an Mw value
      of 3.6*104Da and a mannose/galactose (M/G) ratio of 1.47 was precipitated
      initially, followed by PHGG F2 and F3 which showed lower Mw and higher M/G ratio.
      According to the structure analysis, the distribution of alpha-d-galactose of
      PHGG F1 was compact and regular, and that of other fractions was more random. A
      suitable beta-mannanase for PHGG production and some useful information of PHGG
      are provided in this paper.

PMID- 28756199
TI  - Consciousness and working memory: Current trends and research perspectives.
AB  - Working memory has long been thought to be closely related to consciousness.
      However, recent empirical studies show that unconscious content may be maintained
      within working memory and that complex cognitive computations may be performed on
      line. This promotes research on the exact relationships between consciousness and
      working memory. Current evidence for working memory being a conscious as well as
      an unconscious process is reviewed. Consciousness is shown to be considered a
      subset of working memory by major current theories of working memory. Evidence
      for unconscious elements in working memory is shown to come from visual masking
      and attentional blink paradigms, and from the studies of implicit working memory.
      It is concluded that more research is needed to explicate the relationship
      between consciousness and working memory. Future research directions regarding
      the relationship between consciousness and working memory are discussed.

PMID- 28756200
TI  - ErbB4 protects against neuronal apoptosis via activation of YAP/PIK3CB signaling
      pathway in a rat model of subarachnoid hemorrhage.
AB  - Neuronal apoptosis is a central pathological process in subarachnoid hemorrhage
      (SAH)-induced early brain injury. Previous studies indicated that ErbB4 (EGFR
      family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) is
      essential for normal development and maintenance of the nervous system. In this
      study, we explored the neuroprotective effects of ErbB4 and its downstream YAP
      (yes-associated protein)/PIK3CB signaling pathway in early brain injury after SAH
      in a rat model using the endovascular perforation method. Rats were
      neurologically evaluated with the Modified Garcia Scale and beam balance test at
      24h and 72h after SAH. An ErbB4 activator Neuregulin 1beta1 (Nrg 1beta1), ErbB4
      siRNA and YAP siRNA were used to explore this pathway. The expression of p-ErbB4
      and YAP was significantly increased after SAH. Multiple immunofluorescence
      labeling experiments demonstrated that ErbB4 is mainly expressed in neurons.
      Activation of ErbB4 and its downstream signals improved the neurological deficits
      after SAH and significantly reduced neuronal cell death. Inhibition of ErbB4
      reduced YAP and PIK3CB expression, and aggravated cell apoptosis. YAP knockdown
      reduced the PIK3CB level and eliminated the anti-apoptotic effects of ErbB4
      activation. These findings indicated that ErbB4 plays a neuroprotective role in
      early brain injury after SAH, possibly via the YAP/PIK3CB signaling pathway.

PMID- 28756201
TI  - Multiple mild traumatic brain injury in the rat produces persistent pathological
      alterations in the brain.
AB  - Multiple mild traumatic brain injury (mmTBI), in certain cases, produces
      persistent symptoms. However, the molecular mechanisms underlying these symptoms
      remain unclear. Here, we demonstrate extended pathological changes in the rat
      brain following mmTBI. Using the lateral fluid percussion (LFP) technique we
      exposed adult male Wistar rats to a mild TBI (mTBI) once a week for four weeks
      and compared them to surgical shams. At 90days following the last TBI or sham
      procedure the animals were cognitively tested in the Morris Water Maze (MWM),
      euthanized, and the brains removed for immunohistochemistry. At 90days following
      the last mTBI, NRF-2 staining was significantly decreased in the hilus of the
      hippocampus and cortex on the injured side, but did not significantly differ from
      shams on the un-injured side. CD68 positive microglia were significantly
      increased in the ipsilateral corpus callosum, cortex, and internal capsule of
      injured animals. Reactive astrocytosis, determined by increased GFAP staining,
      was also evident in the corpus callosum, cortex, internal capsule and thalamus on
      the injured side. Interestingly, the corpus callosum thickness at the midline was
      decreased in injured animals and had evident demyelination when compared to sham
      animals. Despite these findings, there were no significant differences in
      neurological assessments at 90days following the last injury. In MWM testing
      there were not significant differences in the training phase, the time spent in
      the thigmotaxia zone, or the target quadrant during the probe trial. However,
      there were significant differences between shams and injured animals in platform
      zone crossings during the probe trial. These results demonstrate that repetitive
      head trauma may produce persistent, long-term pathological alterations in brain
      architecture that may be difficult to detect using standard cognitive and
      neurological assessments.

PMID- 28756202
TI  - Corrigendum to: 'Shunting of Syringomyelic Cavities by Using a Myringotomy Tube:
      Technical Note and Long-Term Results' [World Neurosurgery 98 (2017) 1-5].

PMID- 28756203
TI  - Quantifying the allosteric interactions within a G-protein-coupled receptor
      heterodimer.
AB  - G-protein-coupled receptors are central to signal transduction and cell
      communication. The possibility that cells use receptor heteromerization to
      modulate individual receptor pathways is a surmise that cannot be precluded.
      Given the complexity of these processes, mathematical models contribute to
      understanding how receptors and their respective ligands regulate signaling.
      Here, a mathematical model is presented that quantifies the allosteric
      interactions within a receptor heterodimer. The model is based on the operational
      model of allosterism including constitutive receptor activity, which provides the
      pharmacological analysis of heteromerization with well-established and widely
      used modeling and fitting procedures.

PMID- 28756204
TI  - Cocrystal formation, crystal structure, solubility and permeability studies for
      novel 1,2,4-thiadiazole derivative as a potent neuroprotector.
AB  - The cocrystallization approach has been applied to modify the poor solubility
      profile of the biologically active 1,2,4-thiadiazole derivative (TDZ). Extensive
      cocrystal screening with a library of coformers resulted in formation of a new
      solid form of TDZ with vanillic acid in a 1:1 molar ratio. The cocrystalline
      phase was identified and characterized by thermal and diffraction analyses
      including single-crystal X-ray diffraction. The energies of intermolecular
      interactions in the crystal were calculated by solid-state DFT and PIXEL methods.
      Both calculation schemes show good consistency in terms of total energy of the
      intermolecular interactions and suggest that the cocrystal is mainly stabilized
      via hydrogen bonds, which provide ca. 44% of the lattice energy. Since the
      cocrystal contained the hydroxybenzoic acid derivative as a coformer, the
      solubility profile of the cocrystal was investigated at different pHs using
      eutectic concentrations of the components. Furthermore, the influence of the
      cocrystallization on the permeability performance of the 1,2,4-thiadiazole
      through an artificial regenerated cellulose membrane was also evaluated. In
      addition, the thermodynamic functions of the cocrystal formation were estimated
      from the solubility of the cocrystal and the corresponding solubility of the pure
      compounds at various temperatures. The cocrystal formation process was found to
      have a relatively small value of the driving force (-5.3kJ.mol-1). The most
      significant contribution to the Gibbs energy was provided by the exothermic
      enthalpy of formation.

PMID- 28756205
TI  - Melanin binding study of clinical drugs with cassette dosing and rapid
      equilibrium dialysis inserts.
AB  - Melanin pigment is a negatively charged polymer found in pigmented human tissues.
      In the eye, iris, ciliary body, choroid and retinal pigment epithelium (RPE) are
      heavily pigmented. Several drug molecules are known to bind to melanin, but
      larger sets of drugs have not been compared often in similar test conditions. In
      this study, we introduce a powerful tool for screening of melanin binding. The
      binding of a set of 34 compounds to isolated porcine RPE melanin was determined
      by cassette (n-in-one) dosing in rapid equilibrium dialysis inserts and the
      binding was quantitated with LC-MS/MS analytics. The compounds represented large
      variety in melanin binding (from 8.6%, ganciclovir) to over 95% bound (ampicillin
      and ciprofloxacin). The data provides information on melanin binding of small
      molecular weight compounds that are used for ocular (e.g. brinzolamide,
      ganciclovir) and systemic (e.g. tizanidine, indomethacin) therapy. Interestingly,
      competition among compounds was seen for melanin binding and the binding did not
      show any correlation with plasma protein binding. These results increase the
      understanding of melanin binding of ocular drugs and can be further exploited to
      predict pharmacokinetics in the eye. Pigment binding provides an interesting
      option for improved drug distribution to retina and choroid that are difficult
      target tissues in drug delivery.

PMID- 28756207
TI  - Pregnane X receptor (PXR) deficiency improves high fat diet-induced obesity via
      induction of fibroblast growth factor 15 (FGF15) expression.
AB  - Obesity has become a significant global health problem, and is a high risk factor
      for a variety of metabolic diseases. Fibroblast growth factor (FGF) 15 plays an
      important role in the regulation of metabolism. Xenobiotic-sensing nuclear
      receptors pregnane X receptor (PXR/NR1I2) and constitutive androstane receptor
      (CAR/NR1I3) play important roles in xenobiotic detoxification and metabolism, and
      also are involved in the regulation of energy metabolism. However, the effects
      that PXR and CAR have on the regulation of FGF15 are unknown. Here, we found that
      body weight, hepatic triglyceride levels, liver steatosis, and hepatic mRNA
      expression levels of cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12alpha
      hydroxylase (CYP8B1), the key enzymes in the bile acid classical synthesis
      pathway, were significantly decreased in high fat diet (HFD)-fed PXR knockout
      (KO) mice compared to HFD-fed wild-type mice. Interestingly, intestinal FGF15
      expression levels were significantly elevated in HFD-fed PXR KO mice compared
      with HFD-fed wild-type mice. Additionally, serum total bile acid levels were
      significantly decreased in PXR KO mice than those in wild-type mice when fed a
      control diet or HFD. Total lipids in feces were significantly increased in HFD
      fed PXR KO mice compared to HFD-fed wild-type mice. However, these alterations
      were not found in HFD-fed CAR KO mice. These results indicate that PXR deficiency
      improves HFD-induced obesity via induction of FGF15 expression, resulting in
      suppression of bile acid synthesis and reduction of lipid absorption, hepatic
      lipid accumulation and liver triglyceride levels. Our findings suggest that PXR
      may negatively regulate FGF15 expression and represent a potential therapeutic
      target for the treatment for metabolic disorders such as obesity.

PMID- 28756206
TI  - Entanglement of GSK-3beta, beta-catenin and TGF-beta1 signaling network to
      regulate myocardial fibrosis.
AB  - Nearly every form of the heart disease is associated with myocardial fibrosis,
      which is characterized by the accumulation of activated cardiac fibroblasts (CFs)
      and excess deposition of extracellular matrix (ECM). Although, CFs are the
      primary mediators of myocardial fibrosis in a diseased heart, in the traditional
      view, activated CFs (myofibroblasts) and resulting fibrosis were simply
      considered the secondary consequence of the disease, not the cause. Recent
      studies from our lab and others have challenged this concept by demonstrating
      that fibroblast activation and fibrosis are not simply the secondary consequence
      of a diseased heart, but are crucial for mediating various myocardial disease
      processes. In regards to the mechanism, the vast majority of literature is
      focused on the direct role of canonical SMAD-2/3-mediated TGF-beta signaling to
      govern the fibrogenic process. Herein, we will discuss the emerging role of the
      GSK-3beta, beta-catenin and TGF-beta1-SMAD-3 signaling network as a critical
      regulator of myocardial fibrosis in the diseased heart. The underlying molecular
      interactions and cross-talk among signaling pathways will be discussed. We will
      primarily focus on recent in vivo reports demonstrating that CF-specific genetic
      manipulation can lead to aberrant myocardial fibrosis and sturdy cardiac
      phenotype. This will allow for a better understanding of the driving role of CFs
      in the myocardial disease process. We will also review the specificity and
      limitations of the currently available genetic tools used to study myocardial
      fibrosis and its associated mechanisms. A better understanding of the GSK-3beta,
      beta-catenin and SMAD-3 signaling network may provide a novel therapeutic target
      for the management of myocardial fibrosis in the diseased heart.

PMID- 28756208
TI  - Activation of ALDH1A1 in MDA-MB-468 breast cancer cells that over-express CYP2J2
      protects against paclitaxel-dependent cell death mediated by reactive oxygen
      species.
AB  - Cytochrome P450 2J2 (CYP2J2) expression is elevated in breast and other tumours,
      and is known to be protective against cytotoxic agents that may be used in cancer
      chemotherapy. This study evaluated the mechanisms by which MDA-MB-468 breast
      cancer cells that stably expressed CYP2J2 (MDA-2J2 cells) were protected against
      killing by the anti-cancer agent paclitaxel. Compared to control cells caspase
      3/7 activation by paclitaxel was lower in MDA-2J2 cells, while cell proliferation
      and colony formation following paclitaxel treatment were increased. Basal lipid
      peroxidation was lower in MDA-2J2 cells than in control cells, and the paclitaxel
      mediated increase in peroxidation was attenuated. The mitochondrial complex III
      inhibitor antimycin A modulated basal and paclitaxel-activated reactive oxygen
      species (ROS) formation in control cells; paclitaxel-activated ROS production was
      also modulated by the NADPH oxidase inhibitor diphenyleneiodonium. Paclitaxel
      increased the formation of protein adducts by the reactive aldehyde 4
      hydroxynonenal that is produced by lipid peroxidation; adduct formation was
      attenuated in MDA-2J2 cells. ALDH1A1 expression and activity was strongly
      upregulated in MDA-2J2 cells that was attributed to CYP2J2-derived 14,15
      epoxyeicosatrienoic acid (14,15-EET); the 8,9- and 11,12-EET regioisomers did not
      activate ALDH1A1 expression. Silencing of ALDH1A1 restored the sensitivity of MDA
      2J2 cells to paclitaxel, as indicated by a more pronounced decrease in
      proliferation, and greater increases in caspase activity and formation of ROS to
      levels comparable with control cells. Similar findings were observed with
      doxorubicin, sorafenib and staurosporine, that also promoted ROS-mediated cell
      death that was attenuated in MDA-2J2 cells and reversed by ALDH1A1 gene
      silencing. These findings implicate ALDH1A1 as an important gene that is
      activated in MDA-MB-468-derived cells that contain high levels of CYP2J2. ALDH1A1
      modulates the production of ROS by anti-cancer agents such as paclitaxel and
      diminishes their efficacy. Future approaches could adapt this information to
      facilitate the targeting of ALDH1A1 to promote the efficacy of ROS-generating
      cytotoxic agents and enhance the treatment of breast cancer.

PMID- 28756209
TI  - Antibacterial activity of chensinin-1b, a peptide with a random coil
      conformation, against multiple-drug-resistant Pseudomonas aeruginosa.
AB  - Nosocomial infections caused by Pseudomonas aeruginosa are difficult to treat due
      to the low permeability of its outer membrane as well as to its remarkable
      ability to acquire further resistance to antibiotics. Chensinin-1b exhibited
      antibacterial activity against the tested multiple-drug-resistant bacteria with a
      MIC ranging between 1.56 and 50MUM, except E. cloacae strain 0320 (MREC0320), P.
      fluorescens strain 0322 (MRPF0322) and E. aerogenes strain 0320 (MREA0320).
      However, the MIC (25MUM) of chensinin-1b to multiple-drug-resistant P. aeruginosa
      strain (MRPA 0108) was 16-fold higher than that observed to P. aeruginosa
      susceptible strain CGMCC 1.860 (PA1860). Chensinin-1b was able to disturb the
      integration of the cytoplasmic membrane of PA1860 and MRPA0108 cells similarly,
      but the outer membrane permeability of MRPA0108 cells was significantly lower.
      This low permeability was associated with increased expression of
      lipopolysaccharide (LPS) in the outer membrane and a decrease in negatively
      charged phospholipids in the outer membrane leaflet. In addition, the biofilm of
      MRPA0108 was responsible for the reduced susceptibility to chensinin-1b. A higher
      concentration of chensinin-1b (12.5uM) was required to maximally inhibit the
      formation of MRPA0108 biofilm. Notably, chensinin-1b inhibited the formation of
      MRPA0108 biofilm at concentrations below its MIC value by down-regulating the
      level of PelA, algD, and PslA gene transcription. Importantly, chensinin-1b had a
      significant antibacterial effect against MRPA0108 in vivo. Administration of
      chensinin-1b to mice infected with MRPA 0108 significantly increased survival by
      50-70%. Moreover, chensinin-1b reduced the production of pro-inflammatory
      mediators and correspondingly reduced lung and liver tissue damage in the mouse
      model of septic shock induced by MRPA 0108. Collectively, these results suggest
      that chensinin-1b could be an effective antibiotic against multiple-drug
      resistant bacterial strains.

PMID- 28756210
TI  - The role of epigenomic alterations in furan-induced hepatobiliary pathologies.
AB  - Furan, a volatile heterocyclic organic chemical found in a wide spectrum of
      common human foods, is a liver toxicant and carcinogen in mice and rats. The
      carcinogenic effects of furan have been attributed to genotoxic and non-genotoxic
      mechanisms. Among the broad range of non-genotoxic alterations induced by furan,
      epigenetic alterations are of special interest because of their connection to all
      other non-genotoxic events. This review summarizes current evidence of
      alterations for epigenetic mechanisms, including cytosine DNA methylation,
      histone modifications, and microRNA expression, caused by furan exposure and
      highlights the role of these aberrations in furan-associated hepatobiliary
      pathologies. It also illustrates the potential role of epigenetic alterations as
      indicators for carcinogen exposure and for identification of carcinogens,
      especially those with non-genotoxic mechanisms of action.

PMID- 28756211
TI  - Effects of paternal deprivation on cocaine-induced behavioral response and
      hypothalamic oxytocin immunoreactivity and serum oxytocin level in female
      mandarin voles.
AB  - Early paternal behavior plays a critical role in behavioral development in
      monogamous species. The vast majority of laboratory studies investigating the
      influence of parental behavior on cocaine vulnerability focus on the effects of
      early maternal separation. However, comparable studies on whether early paternal
      deprivation influences cocaine-induced behavioral response are substantially
      lacking. Mandarin vole (Microtus mandarinus) is a monogamous rodent with high
      levels of paternal care. After mandarin vole pups were subjected to early
      paternal deprivation, acute cocaine- induced locomotion, anxiety- like behavior
      and social behavior were examined in 45day old female pups, while hypothalamic
      oxytocin immunoreactivity and serum oxytocin level were also assessed. We found
      that cocaine increased locomotion and decreased social investigation, contact
      behavior and serum oxytocin level regardless of paternal care. Cocaine increased
      anxiety levels and decreased oxytocin immunoreactive neurons of the
      paraventricular nuclei and supraoptic nuclei in the bi-parental care group,
      whilst there were no specific effects in the paternal deprivation group. These
      results indicate that paternal deprivation results in different behavioral
      response to acute cocaine exposure in adolescents, which may be in part
      associated with the alterations in oxytocin immunoreactivity and peripheral OT
      level.

PMID- 28756212
TI  - An analysis of dentate gyrus function (an update).
AB  - In this review there will be a description of the dentate gyrus (DG) neural
      circuitry that mediates the operation of a variety of mnemonic processes
      associated with dorsal and ventral DG function in rats. Dysfunction of the dorsal
      DG can be shown to mediate mnemonic processing of spatially based information
      including a) the operation of conjunctive encoding of multiple sensory inputs to
      determine spatial representations, b) pattern separation based on reducing
      interference between similar spatial locations and spatial contexts for
      horizontal distance between objects, vertical distance for height of objects,
      slope or angle of motor movements, c) importance of spatial context in object
      recognition and processing of shades of grey associated with the walls of the box
      d) temporal integration in the creation of remote memory based in part on DG
      neurogenesis and function of the CA3 subregion of the hippocampus. Dysfunction of
      the ventral DG can be shown to mediate mnemonic processing of odor and reward
      value based information including a) pattern separation for odors and reward
      value, and b) social recognition.

PMID- 28756213
TI  - Noradrenergic antagonists mitigate amphetamine-induced recovery.
AB  - Brain injury, including that due to stroke, leaves individuals with cognitive
      deficits that can disrupt daily aspect of living. As of now there are few
      treatments that shown limited amounts of success in improving functional outcome.
      The use of stimulants such as amphetamine have shown some success in improving
      outcome following brain injury. While the pharmacological mechanisms for
      amphetamine are known; the specific processes responsible for improving
      behavioral outcome following injury remain unknown. Understanding these
      mechanisms can help to refine the use of amphetamine as a potential treatment or
      lead to the use of other methods that share the same pharmacological properties.
      One proposed mechanism is amphetamine's impact upon noradrenaline (NA). In the
      current, study noradrenergic antagonists were administered prior to amphetamine
      to pharmacologically block alpha- and beta-adrenergic receptors. The results
      demonstrated that the blockade of these receptors disrupted amphetamines ability
      to induce recovery from hemispatial neglect using an established aspiration
      lesion model. This suggests that amphetamine's ability to ameliorate neglect
      deficits may be due in part to noradrenaline. These results further support the
      role of noradrenaline in functional recovery. Finally, the development of
      polytherapies and combined therapeutics, while promising, may need to consider
      the possibility that drug interactions can negate the effectiveness of treatment.

PMID- 28756214
TI  - Neonatal fluoxetine exposure modulates serotonergic neurotransmission and disturb
      inhibitory action of serotonin on food intake.
AB  - : The neurotransmitter serotonin (5-HT) acts as an important regulator of the
      critical neurodevelopmental processes and thus alterations in 5-HT signaling
      early promotes permanent structural and functional changes in brain. The
      selective serotonin reuptake inhibitors (SSRIs), as fluoxetine and citalopram,
      blocking serotonin transporter (SERT) at the presynaptic neuron, which regulates
      extracellular 5-HT levels. Evidence suggests that the exposure to SSRIs in the
      neurodevelopmental period may alters 5-HT signaling sensitivity on food intake
      control. The aim of the present study was to evaluate the effects of neonatal
      exposure to fluoxetine on molecular and cellular components of the serotonergic
      system and food intake control in young animals. METHODS: The animals were
      divided according to experimental manipulation, Fluoxetine Group (FG): male pups
      received application of fluoxetine (10mg/kg, 10MUL/g) and Saline Group (SG): male
      pups received saline application (0.9% NaCl, 10MUL/g), both throughout lactation
      (PND1-PND21). They evaluated body weight, food intake, SERT gene and protein
      expression, serotonin content in the hypothalamus. The neonatal exposure to
      fluoxetine promoted reduction in body weight, disturb the serotonin hypophagic
      response, and increase the serotonin and SERT hypothalamic in young animals. We
      conclude that the changes of components of the serotonergic system by neonatal
      exposure to fluoxetine may be responsible for disturb the inhibitory action of
      serotonin on food intake.

PMID- 28756216
TI  - Current controversies in cholangiocarcinoma.
AB  - Cholangiocarcinoma represents 10% of primary liver malignancies and accounts for
      less than 3% of all gastrointestinal malignant tumors, with an enormous
      geographical variation. This neoplasia can arise from the biliary tract
      epithelium or hepatic progenitor cells. Depending on the anatomic localization,
      it is classified into three subtypes: intrahepatic, perihilar and distal. This
      fact is one of the main difficulties, because there are many studies that
      indistinctly include the results in the management of these different types of
      cholangiocarcinoma, without differentiating its location and even including
      gallbladder cancer. There are many controversial points in epidemiology, liver
      transplantation as a treatment, limitations of different results by group and
      type of treatment, histological testing and chemotherapy. This is a narrative
      review about topics in cholangiocarcinoma. This article is part of a Special
      Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales,
      Marco Marzioni, Nicholas LaRusso and Peter Jansen.

PMID- 28756215
TI  - Treadmill running prevents age-related memory deficit and alters neurotrophic
      factors and oxidative damage in the hippocampus of Wistar rats.
AB  - Clinical and pre-clinical studies indicate that exercise is beneficial to many
      aspects of brain function especially during aging. The present study investigated
      the effects of a treadmill running protocol in young (3month-old) and aged
      (22month-old) male Wistar rats, on: I) cognitive function, as assessed by spatial
      reference memory in the Morris water maze; II) oxidative stress parameters and
      the expression of neurotrophic factors BDNF, NT-3, IGF-1 and VEGF in the
      hippocampus. Animals of both ages were assigned to sedentary (non-exercised) and
      exercised (20min of daily running sessions, 3 times per week for 4weeks) groups.
      Cognition was assessed by a reference memory task run in the Morris water maze;
      twenty four hours after last session of behavioral testing hippocampi were
      collected for biochemical analysis. Results demonstrate that the moderate
      treadmill running exercise: I) prevented age-related deficits in reference memory
      in the Morris water maze; II) prevented the age-related increase of reactive
      oxygen species levels and lipid peroxidation in the hippocampus; III) caused an
      increase of BDNF, NT-3 and IGF-1 expression in the hippocampus of aged rats.
      Taken together, results suggest that both exercise molecular effects, namely the
      reduction of oxidative stress and the increase of neurotrophic factors expression
      in the hippocampus, might be related to its positive effect on memory performance
      in aged rats.

PMID- 28756217
TI  - Maternal insulin therapy does not restore foetoplacental endothelial dysfunction
      in gestational diabetes mellitus.
AB  - Pregnant women diagnosed with gestational diabetes mellitus subjected to diet
      (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi).
      GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)
      mediated transport of L-arginine and nitric oxide synthase (NOS) activity in
      foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether
      insulin therapy results in reversal of the GDMd effect on the foetoplacental
      vasculature is unknown. We assayed whether insulin therapy normalizes GDMd
      associated foetoplacental endothelial dysfunction. Primary cultures of human
      umbilical vein endothelial cells (HUVECs) from GDMi pregnancies were used to
      assay L-arginine transport kinetics, NOS activity, p44/42mapk and protein kinase
      B/Akt activation, and umbilical vein rings reactivity. HUVECs from GDMi or GDMd
      show increased hCAT-1 expression and maximal transport capacity, NOS activity,
      and eNOS, and p44/42mapk, but not Akt activator phosphorylation. Dilation in
      response to insulin or calcitonin-gene related peptide was impaired in umbilical
      vein rings from GDMi and GDMd pregnancies. Incubation of HUVECs in vitro with
      insulin (1 nmol/L) restored hCAT-1 and eNOS expression and activity, and eNOS and
      p44/42mapk activator phosphorylation. Thus, maternal insulin therapy does not
      seem to reverse GDMd-associated alterations in human foetoplacental vasculature.

PMID- 28756218
TI  - Occurrence and fate of substituted diphenylamine antioxidants and benzotriazole
      UV stabilizers in various Canadian wastewater treatment processes.
AB  - Substituted diphenylamine antioxidants (SDPAs) and benzotriazole UV stabilizers
      (BZT-UVs) are additives used in industrial and consumer products to prevent
      degradation or color change of materials, but their environmental fate and
      disposition are not well characterized. In this study, SDPAs and BZT-UVs were
      analyzed in 68 liquid and 39 solid samples collected from 9 wastewater treatment
      plants (WWTPs) in Canada to investigate the occurrence and fate of these
      contaminants. The median concentrations of SigmaSDPAs and SigmaBZT-UVs was 483
      and 76.2 ng L-1 in influent, 28.4 and 4.84 ng L-1 in effluent, and 2750 and 457
      ng g-1 in biosolids (dry weight), respectively. Dinonyl-diphenylamine (C9C9) was
      the predominant congener of SDPAs in all matrices (>40%). For target BZT-UVs, the
      major components were 2-(2H-benzotriazol-2-yl)-4,6-bis(1-methyl-1
      phenylethyl)phenol (UV234) and 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol
      (UV328). SDPAs and BZT-UVs were effectively removed (>90%) from the liquid stream
      in most WWTPs mainly through sludge sorption and separation, but
      biotransformation, UV treatment and filtration may also contribute to removal of
      some contaminants in advanced treatment plants. In contrast, the removal
      efficiency of target contaminants using chemically assisted primary treatment was
      low, likely due to the short hydraulic retention time of this site. Our results
      suggest that wastewater effluent is a vector of SDPAs and BZT-UVs to the aquatic
      environment. The results also highlight the high concentrations of SDPAs and BZT
      UVs associated with the solid stream in WWTPs, which could affect the beneficial
      use of biosolids (e.g., compost or land applications).

PMID- 28756219
TI  - Predicting chloroform production from organic precursors.
AB  - Quantitative methods which link molecular descriptors for recognized precursors
      to formation of drinking water disinfection byproducts are scarce. This study
      aimed to develop a simple mathematical tool for predicting chloroform
      (trichloromethane) yields resulting from aqueous chlorination of model organic
      precursors. Experimental chloroform yields from 211 precursors were collated from
      22 literature studies from 1977 onwards. Nineteen descriptors, some established
      and others developed during this study, were used as inputs in a multiple linear
      regression model. The final model, calibrated using five-way leave-many-out cross
      validation, contains three descriptors. Two novel empirical descriptors, which
      quantify the impact of adjacent substituents on aromatic and enolizable chlorine
      substitution sites, were the most significant. The model has r2 = 0.91 and a
      standard error of 8.93% mol/mol. Experimental validation, using 10 previously
      untested precursors, showed a mean discrepancy of 5.3% mol/mol between
      experimental and predicted chloroform yields. The model gives insight to the
      influence that specific functional groups, including hydroxyl, chlorine and
      carboxyl, have on chloroform formation and the relative contributions made by
      separate substitution sites in the same molecule. It is anticipated that the
      detailed approach can be updated and extended as new experimental data emerges,
      to encompass additional precursors and groups of disinfection byproducts.

PMID- 28756220
TI  - Linking terrestrial phosphorus inputs to riverine export across the United
      States.
AB  - Humans have greatly accelerated phosphorus (P) flows from land to aquatic
      ecosystems, causing eutrophication, harmful algal blooms, and hypoxia. A variety
      of statistical and mechanistic models have been used to explore the relationship
      between P management on land and P losses to waterways, but our ability to
      predict P losses from watersheds often relies on small scale catchment studies,
      where detailed measurements can be made, or global scale models that that are
      often too coarse-scaled to be used directly in the management decision-making
      process. Here we constructed spatially explicit datasets of terrestrial P inputs
      and outputs across the conterminous U.S. (CONUS) for 2012. We use this dataset to
      improve understanding of P sources and balances at the national scale and to
      investigate whether well-standardized input data at the continental scale can be
      used to improve predictions of hydrologic P export from watersheds across the
      U.S. We estimate that in 2012 agricultural lands received 0.19 Tg more P as
      fertilizer and confined manure than was harvested in major crops. Approximately
      0.06 Tg P was lost to waterways as sewage and detergent nationally based on per
      capita loads in 2012. We compared two approaches for calculating non-agricultural
      P waste export to waterways, and found that estimates based on per capita P loads
      from sewage and detergent were 50% greater than Discharge Monitoring Report
      Pollutant Loading Tool. This suggests that the tool is likely underestimating P
      export in waste the CONUS scale. TP and DIP concentrations and TP yields were
      generally correlated more strongly with runoff than with P inputs or P balances,
      but even the relationships between runoff and P export were weak. Including P
      inputs as independent variables increased the predictive capacity of the best-fit
      models by at least 20%, but together inputs and runoff explained 40% of the
      variance in P concentration and 46-54% of the variance in P yield. By developing
      and applying a high-resolution P budget for the CONUS this study confirms that
      both hydrology and P inputs and sinks play important roles in aquatic P loading
      across a wide range of environments.

PMID- 28756221
TI  - The public health significance of latrines discharging to groundwater used for
      drinking.
AB  - Faecal contamination of groundwater from pit latrines is widely perceived as a
      major threat to the safety of drinking water for several billion people in rural
      and peri-urban areas worldwide. On the floodplains of the Ganges-Brahmaputra
      Meghna delta in Bangladesh, we constructed latrines and monitored piezometer
      nests monthly for two years. We detected faecal coliforms (FC) in 3.3-23.3% of
      samples at four sites. We differentiate a near-field, characterised by high
      concentrations and frequent, persistent and contiguous contamination in all
      directions, and a far-field characterised by rare, impersistent, discontinuous
      low-level detections in variable directions. Far-field FC concentrations at four
      sites exceeded 0 and 10 cfu/100 ml in 2.4-9.6% and 0.2-2.3% of sampling events
      respectively. The lesser contamination of in-situ groundwater compared to water
      at the point-of-collection from domestic wells, which itself is less contaminated
      than at the point-of-consumption, demonstrates the importance of recontamination
      in the well-pump system. We present a conceptual model comprising four sub
      pathways: the latrine-aquifer interface (near-field); groundwater flowing from
      latrine to well (far-field); the well-pump system; and post-collection handling
      and storage. Applying a hypothetical dose-response model suggests that 1-2% of
      the diarrhoeal disease burden from drinking water is derived from the aquifer,
      29% from the well-pump system, and 70% from post-collection handling. The
      important implications are (i) that leakage from pit latrines is a minor
      contributor to faecal contamination of drinking water in alluvial-deltaic
      terrains; (ii) fears of increased groundwater pollution should not constrain
      expanding latrine coverage, and (iii) that more attention should be given to
      reducing contamination around the well-head.

PMID- 28756222
TI  - Role of LncRNA TUG1 in intervertebral disc degeneration and nucleus pulposus
      cells via regulating Wnt/beta-catenin signaling pathway.
AB  - OBJECTIVE: To investigate the role of TUG1 in intervertebral disc degeneration
      (IDD) and human nucleus pulposus cells (NPCs) via regulating Wnt/beta-catenin
      pathway. METHODS: The study collected nucleus pulposus (NP) tissue samples from
      30 patients with lumbar disc herniation (LDH) (Case group) and 18 patients with
      lumbar spine trauma (Control group). NPCs induced by TNF-alpha in vitro were
      divided into Blank, Vector, TUG1, TUG1-siRNA, XAV-939, TUG1 + XAV-939 groups. qRT
      PCR was used to detect the expression of TUG1 and ECM-related genes, Western blot
      to determine the expression of Wnt/beta-catenin pathway and apoptosis-related
      proteins, and ELISA to measure the expression of ECM-related proteins. The
      apoptosis was detected by TUNEL and Annexin V-FITC/PI double-staining. The
      proliferation and senescence were tested by CCK-8 and SA-beta-gal staining
      respectively. RESULTS: TUG1 was upregulated in patients with IDD, which was
      positively related to Wnt and beta-catenin. Besides, TUG1, Wnt1 and beta-catenin
      were greatly increased in the NPCs after TNF-alpha induction. Compared with the
      Blank group, TUG1-siRNA and XAV-939 can appreciably down-regulate the expressions
      of Wnt1, beta-catenin, Caspase-3, Bax, MMP3 and ADAMTS5, up-regulate the
      expression of Bcl-2, Aggrecan and COL2A1, inhibit the apoptosis and senescence,
      and promote cell proliferation; however, the TUG1 group had the completely
      opposite results. CONCLUSION: Silencing TUG1 may not only protect human NPCs from
      TNF-alpha-induced apoptosis and senescence, but also promote cell proliferation
      by blocking Wnt/beta-catenin pathway, which provides a theoretical basis for the
      clinical treatment of IDD.

PMID- 28756223
TI  - BEBT-908: A novel potent PI3K/HDAC inhibitor against diffuse large B-cell
      lymphoma.
AB  - The PI3K pathway and epigenetic regulation have been shown to play a pivotal role
      in the development and progression of diffuse large B-cell lymphoma (DLBCL). In
      the clinic, existing PI3K and HDAC inhibitors show limited efficacy as single
      agents toward DLBCL. However, in preclinical studies, the synergistic effects of
      PI3K inhibitors and HDAC inhibitors on DLBCL have sparked the enthusiasm of
      researchers to target both PI3K and HDAC. We hypothesized that a novel dual
      PI3K/HDAC inhibitor, BEBT-908, would display improved pharmacologic effects on
      DLBCL. We analyzed the anti-DLBCL activity of BEBT-908 in a comprehensive manner,
      demonstrating its role in the suppression of in vitro cell proliferation,
      blockade of PI3K and HDAC activities, inhibition of multiple signaling pathways,
      and promotion of apoptosis and cell cycle arrest. BEBT-908 showed potent
      PI3K/HDAC inhibition, with nanomolar IC50 values against DLBCL cell lines.
      Moreover, BEBT-908 inhibited multiple pathways, including JAK/STAT3, MAPK/ERK and
      NF-kappaB, and induced apoptosis and cell cycle arrest at G1 phase in these
      cells. Additionally, dual PI3K/HDAC inhibition was superior to the inhibition of
      PI3K or HDAC alone. The dual inhibitor BEBT-908 is a promising lead compound for
      developing novel targeted therapeutic agents against DLBCL.

PMID- 28756224
TI  - Treatment with a programmed cell death-1-specific antibody has little effect on
      afatinib- and naphthalene-induced acute pneumonitis in mice.
AB  - Although several antibodies developed to target programmed cell death-1 (PD-1)
      and its ligand (PD-L1) have demonstrated great promise for the treatment of non
      small cell lung cancer (NSCLC), and other malignancies, these therapeutic
      antibodies can cause pneumonitis. Furthermore, epidermal growth factor receptor
      tyrosine kinase inhibitor (EGFR-TKI)-induced pneumonitis was reported after
      treatment with anti PD-1 antibodies. We previously demonstrated that mice with
      naphthalene-induced airway epithelial injury developed severe gefitinib-induced
      pneumonitis through a neutrophil-dependent mechanism. The present study aimed to
      investigate whether treatment with afatinib, an EGFR-TKI that effectively targets
      EGFR mutation-positive NSCLC, and anti PD-1 antibodies induces pneumonitis in
      mice. C57BL/6J mice were treated intraperitoneally with naphthalene (200 mg/kg)
      on day 0. Afatinib (20 mg/kg) was administered orally on days -1 to 13. An anti
      PD-1 antibody (0.2 mg/mice) was also administered intraperitoneally every 3 days
      from day 1 until day 13. The bronchoalveolar lavage fluid (BALF) and lung tissues
      were sampled on day 14. As observed previously with gefitinib, afatinib
      significantly increased the severity of histopathologic findings and the level of
      protein in BALF on day 14, compared to treatment with naphthalene alone. A
      combined anti-PD-1 antibody and afatinib treatment after naphthalene
      administration had yielded the same histopathological grade of lung inflammation
      as did afatinib treatment alone. Our results suggest that anti-PD-1 antibody
      treatment has little effect on afatinib-induced lung injury.

PMID- 28756225
TI  - Identification of novel resistance mechanisms to NAMPT inhibition via the de novo
      NAD+ biosynthesis pathway and NAMPT mutation.
AB  - Cancer cells have an unusually high requirement for the central and intermediary
      metabolite nicotinamide adenine dinucleotide (NAD+), and NAD+ depletion
      ultimately results in cell death. The rate limiting step within the NAD+ salvage
      pathway required for converting nicotinamide to NAD+ is catalyzed by nicotinamide
      phosphoribosyltransferase (NAMPT). Targeting NAMPT has been investigated as an
      anti-cancer strategy, and several highly selective small molecule inhibitors have
      been found to potently inhibit NAMPT in cancer cells, resulting in NAD+ depletion
      and cytotoxicity. To identify mechanisms that could cause resistance to NAMPT
      inhibitor treatment, we generated a human fibrosarcoma cell line refractory to
      the highly potent and selective NAMPT small molecule inhibitor, GMX1778. We
      uncovered novel and unexpected mechanisms of resistance including significantly
      increased expression of quinolinate phosphoribosyl transferase (QPRT), a key
      enzyme in the de novo NAD+ synthesis pathway. Additionally, exome sequencing of
      the NAMPT gene in the resistant cells identified a single heterozygous point
      mutation that was not present in the parental cell line. The combination of
      upregulation of the NAD+ de novo synthesis pathway through QPRT over-expression
      and NAMPT mutation confers resistance to GMX1778, but the cells are only
      partially resistant to next-generation NAMPT inhibitors. The resistance
      mechanisms uncovered herein provide a potential avenue to continue exploration of
      next generation NAMPT inhibitors to treat neoplasms in the clinic.

PMID- 28756226
TI  - Specific packaging and circulation of cytochromes P450, especially 2E1 isozyme,
      in human plasma exosomes and their implications in cellular communications.
AB  - Cytochrome P450 (CYP) enzymes metabolize the majority of xenobiotics and are
      mainly found in hepatic and some extra-hepatic cells. However, their presence and
      functional role in exosomes, small extracellular vesicles that are secreted from
      various cells into extracellular fluids including plasma, is unknown. In this
      study, we analyzed the expression and biological activity of CYP enzymes in human
      plasma exosomes. First, we optimized isolation of plasma exosomes and
      characterized them for their physical properties and quality. The results showed
      that the purity of exosomes (<200 nm) improved upon prior filtration of plasma
      using a 0.22 micron filter. We then analyzed the relative level of exosomal CYP
      mRNAs, proteins, and enzyme activity. The results showed that the relative level
      of CYP enzymes in exosomes is higher than in plasma, suggesting their specific
      packaging in exosomes. Of the seven CYP enzymes tested, the mRNA of CYP1B1,
      CYP2A6, CYP2E1, and CYP3A4 were detectable in exosomes. Interestingly, the
      relative level of CYP2E1 mRNA was >500-fold higher than the other CYPs. The
      results from the Western blot showed detectable levels of CYP1A1, CYP1B1, CYP2A6,
      CYP2E1, and CYP3A4. Our results also demonstrated that exosomal CYP2E1 and CYP3A4
      show appreciable activity relative to their respective positive controls (CYP
      induced baculosomes). Our results also showed that CYP2E1 is expressed relatively
      higher in plasma exosomes than hepatic and monocytic cells and exosomes derived
      from these cells. In conclusion, this is the first evidence of the specific
      packaging and circulation of CYP enzymes, especially CYP2E1, in human plasma
      exosomes. The findings have biological and clinical significance in terms of
      their implications in cellular communications and potential use of plasma
      exosomal CYPs as biomarkers.

PMID- 28756227
TI  - Low-dose G-CSF improves fat graft retention by mobilizing endogenous stem cells
      and inducing angiogenesis, whereas high-dose G-CSF inhibits adipogenesis with
      prolonged inflammation and severe fibrosis.
AB  - BACKGROUND: Hematopoietic stem cells (HSCs) promote fat graft survival by
      modulating its revascularization. The authors hypothesize that mobilization of
      HSCs by G-CSF will improve fat graft survival. Hence, we evaluated the effect of
      different doses of G-CSF on fat grafting. METHODS: Male 8-week-old C57 mice
      received high-dose G-CSF (100 MUg/kg), low-dose G-CSF (10 MUg/kg), and PBS
      (control) intraperitoneally for 7 consecutive days right after autologous fat
      grafting. Grafted fat was harvested at 1, 4, and 12 weeks for examination.
      RESULTS: The low-dose G-CSF, high-dose G-CSF, and control groups had retention
      rates of 73.6% +/- 3.1%, 51.6% +/- 4.4%, and 44.5% +/- 4.0%, respectively, at 12
      weeks (low-dose G-CSF versus control and low-dose G-CSF versus high-dose G-CSF,
      both p < 0.05; no significant difference between high-dose G-CSF and control
      group). Both doses of G-CSF successfully mobilized HSCs into circulation and
      upregulated the level of blood-derived stem cells in fat grafts, contributing to
      improved angiogenesis. However, high-dose G-CSF caused a prolonged macrophage
      infiltration and elevated level of inflammation (IL-6 and TNF-alpha), which led
      to severe fibrosis and impaired adipogenesis (downregulated expression of PPAR
      gamma and CEBP-alpha). CONCLUSIONS: Low-dose G-CSF treatment successfully
      improved fat graft survival by mobilizing HSCs and inducing angiogenesis.
      However, high-dose G-CSF prolonged inflammation and caused severe fibrosis,
      leading to impaired adipogenesis and poor fat graft survival.

PMID- 28756228
TI  - Blocking LDHA glycolytic pathway sensitizes glioblastoma cells to radiation and
      temozolomide.
AB  - PURPOSE: Up-regulation of lactate dehydrogenase LDHA, is a frequent event in
      human malignancies and relate to poor postoperative outcome. In the current study
      we examined the hypothesis that LDHA and anaerobic glycolysis, may contribute to
      the resistance of glioblastoma to radiotherapy and to temozolomide. METHODS AND
      MATERIALS: The expression of LDH5 isoenzyme (fully encoded by the LDHA gene) was
      assessed in human glioblastoma tissues. Experimental in vitro studies involved
      the T98 and U87 glioblastoma cell lines. Their sensitivity to radiotherapy and to
      temozolomide, following silencing of LDHA gene or following exposure to the LDHA
      chemical inhibitor 'oxamate' and to the glycolysis inhibitor '2-deoxy-d-glucose'
      (2DG), was studied. RESULTS: Glioblastoma tissues showed strong cytoplasmic and
      nuclear LDH5 expression in 0-90% (median 20%) of the neoplastic cells. T98 and
      U87 cell lines showed that blocking glycolysis, either with LDHA gene silencing
      or exposure to oxamate (30 mM) and blockage of glycolysis with 2DG (500 MUM),
      results in enhanced radiation sensitivity, an effect that was more robust in the
      T98 radioresistant cell line. Furthermore, all three glycolysis targeting
      methods, significantly sensitized both cell lines to Temozolomide. CONCLUSIONS:
      The current study provides evidence that a large subgroup of human glioblastomas
      are highly glycolytic, and that inhibitors of glycolysis, like LDHA targeting
      agents, may prove of therapeutic importance by enhancing the efficacy of
      radiotherapy and temozolomide against this lethal disease.

PMID- 28756229
TI  - Role of the extracellular matrix-located Mac-2 binding protein as an interactor
      of the Wnt proteins.
AB  - The Wnt proteins constitute a conserved family of secreted palmitoleate
      containing signaling proteins that play important roles in development and tissue
      homeostasis. Their hydrophobic nature has raised the question of how the proteins
      are transported outside the cells. Accumulating evidence suggests that several
      different mechanisms, including transport by lipoprotein particles and exosomes,
      may contribute to this process. Here, we expressed epitope-tagged Wnt4 in HEK293
      cells, and identified Mac-2 binding protein (Mac-2BP) as its binding partner in
      the serum-free conditioned medium. Serine-to-alanine substitution at the
      conserved fatty acid-conjugation site did not affect Mac-2BP binding. Subsequent
      studies showed that Mac-2BP may be a general Wnt interactor. It is found in the
      extracellular matrix (ECM) of various tissues, where it forms unusual oligomeric
      ring-like structures. Its functions appear to include interactions with cells and
      certain ECM components. Intriguingly, both Wnt signaling and Mac-2BP expression
      are upregulated in many types of cancer. Our studies on the four-domain Mac-2BP
      indicate a crucial role in Wnt binding for the C-terminal domain that bears no
      sequence similarity to any other protein. Mac-2BP may have a role in regulating
      the extracellular spreading and storage of the Wnts, thereby modulating their
      bioavailability and stability.

PMID- 28756230
TI  - Haloperidol, a sigma receptor 1 antagonist, promotes ferroptosis in
      hepatocellular carcinoma cells.
AB  - Ferroptosis is a novel form of cell death, which is characterized by accumulation
      of reactive oxygen species (ROS). Sigma 1 receptor (S1R) has been suggested to
      function in oxidative stress metabolism. Both erastin and sorafenib significantly
      induced S1R protein expression. Haloperidol strongly promoted erastin- and
      sorafenib-induced cell death, which was blocked by ferrostatin-1 but not ZVAD-FMK
      or necrosulfonamide. During ferroptosis, haloperidol substantially increased the
      cellular levels of Fe2+, GSH and lipid peroxidation. Furthermore, several
      ferroptosis-related protein targets were up-regulated in the absence of
      haloperidol. Thus, Our study identified an association between haloperidol and
      ferroptosis for the first time. Our analyses of a combination of drugs may
      provide a novel strategy of hepatocellular carcinoma (HCC) therapy.

PMID- 28756231
TI  - Pah1p negatively regulates the expression of V-ATPase genes as well as vacuolar
      acidification.
AB  - In yeast, PAH1 plays an important role in cell homeostasis and lipid
      biosynthesis. PAH1 encodes for the PA phosphatase, Pah1p, which is responsible
      for de novo TAG and phospholipid synthesis. It has been suggested that the lack
      of Pah1p causes irregular vacuolar morphology and dysfunctional V-ATPase pump
      activity. However, the molecular connection between Pah1p and V-ATPase activity
      has remained unclear. Through real-time PCR, we have shown that PAH1 is maximally
      induced at the stationary stage in the presence of inositol. We also found that
      vacuoles were less fragmented when PAH1 is maximally expressed. Subsequently, we
      observed that vacuoles from pah1Delta cells were more acidic than those in WT
      cells. Furthermore, V-ATPase genes were upregulated in the absence of Pah1p.
      These results suggest that Pah1p plays an important role in vacuolar activity by
      negatively regulating the expression of V-ATPase genes. As such, we provide
      evidence to show the role of Pah1p in vacuolar acidification and fragmentation.

PMID- 28756232
TI  - Tim3/galectin-9 alleviates the inflammation of TAO patients via suppressing
      Akt/NF-kB signaling pathway.
AB  - Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease. Studies showed
      that T helper 1 (Th1), Th2, and Th17 cells play important roles in the pathology
      of TAO. Tim-3 and its only known ligand Galectin-9 (Gal-9) is related to the
      suppression of Th1 and Th17 cytokine secretion. This study aims to investigate
      the role of Tim3/Gal-9 in the inflammatory response of TAO. In this study, the
      levels of Tim3, Gal-9, and cytokines of Th1 (TNF-alpha and IFN-gamma), Th2 (IL
      4), and Th17 (IL-17) cells were analyzed in the blood samples of TAO patients and
      healthy controls as well as in orbital fibroblasts. Tim3 overexpression and Gal-9
      neutralizing antibody were used in TAO and LPS-stimulated control orbital
      fibroblasts to further investigate the role and mechanism of Tim3/Gal-9 on the
      inflammation of TAO. We found Tim3 and Gal-9 expression was significantly
      downregulated in TAO patients and further lower in active TAO than inactive TAO
      or controls. Th1, Th2, and Th17 cytokines were all increased in TAO patients. Th1
      and Th17 cytokines were higher in active TAO patients than in inactive TAO
      patients, while Th2 cytokines were enhanced in inactive TAO. Tim3 overexpression
      decreased the levels of Th1 and Th17 cytokines, but not Th2 cytokine in TAO or
      LPS-stimulated control orbital fibroblasts. These effects were abrogated by Gal-9
      neutralizing antibody. Moreover, Tim3 reduced the levels of p-Akt and p-p65 in
      TAO or LPS-induced control orbital fibroblasts that were reversed by Gal-9
      blocking. In conclusion, Tim3/Gal-9 alleviates the inflammation of TAO patients
      via suppressing Akt/NF-kappaB signaling pathway.

PMID- 28756233
TI  - Organoid culture systems to study host-pathogen interactions.
AB  - Recent advances in host-microbe interaction studies in organoid cultures have
      shown great promise and have laid the foundation for much more refined future
      studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral
      organoids have helped us understand its association with microcephaly. Similarly,
      the pathogenesis of bacterial (Helicobacter pylori, Clostridium difficile) and
      viral (Norovirus, Rotaviruses) infections have been precisely dissected in
      organoid cultures. Additionally, direct associations between microbial
      colonization of tissues and diseases like cancer have also been deciphered. Here
      we discuss the most recent and striking studies on host-microbe interactions in
      organoid cultures, highlighting various methods which can be used for developing
      microbe-organoid co-culture systems.

PMID- 28756235
TI  - Diagnosis and Treatment of Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a new disease. It is caused by a T-helper type
      2 cell response to food antigens in contact with the esophageal mucosa. Although
      no single feature defines EoE, a constellation of compatible demographic,
      clinical, endoscopic, and histologic findings establish the diagnosis. Children
      present with symptoms and endoscopic patterns characteristic of inflammation,
      whereas adolescents and adults have manifestations of fibrosis and gross
      esophageal strictures. Clinical and endoscopic scoring systems have helped to
      standardize diagnosis. There is controversy in EoE research over the optimal
      endpoint for treatment. Although the most common endpoint is a reduced number of
      eosinophils in biopsies, changes in symptoms and endoscopic features are becoming
      important targets of therapy. We should improve our understanding of EoE
      progression and the need for maintenance therapy, and continue development of
      diagnostic tools that avoid endoscopy and biopsy analyses to more easily monitor
      disease activity.

PMID- 28756234
TI  - Anti-Tumor Necrosis Factor With a Glyco-Engineered Fc-Region Has Increased
      Efficacy in Mice With Colitis.
AB  - BACKGROUND & AIMS: Although tumor necrosis factor (TNF) antagonists reduce many
      clinical features of inflammatory bowel disease, complete mucosal healing occurs
      in fewer than 50% of patients. The Fc-region of monoclonal antibodies against TNF
      has immunosuppressive properties via effects on macrophage polarization. We
      examined the interaction between the anti-TNF Fc-region and Fcgamma receptors
      (FcgammaR), and whether the absence of the Fc core fucose (which increases
      binding to FcgammaRIIIa) increases the efficacy of anti-TNF in mice with colitis.
      METHODS: We generated Rag1-/- mice that lack all activating FcgammaRs (FcgammaRI,
      FcgammaRIII, and FcgammaRIV; called FcgammaR-/-Rag1-/- mice). We produced hypo
      fucosylated antibodies against mouse and human TNF (adalimumab). Colitis was
      induced in mice by transfer of CD4+CD45RBhi to FcgammaR-/-Rag1-/- or Rag1-/-
      littermates; mice were given different antibodies against TNF or isotype
      (control) antibodies and disease activity index scores were determined. Colon
      tissues were collected and analyzed by histology. Human peripheral blood
      mononuclear cells (PBMCs) were isolated from blood of healthy donors. T-cell
      proliferation and proportions of CD206+ (immune regulatory) macrophages were
      measured in mixed lymphocyte reactions. Human PBMCs were genotyped for FCGR3A158
      (the FcgammaRIIIa-158F allotype displays a lower Fc binding affinity) using the
      TaqMan single nucleotide polymorphism genotype assay. RESULTS: Rag1-/- mice with
      colitis given anti-TNF had near complete mucosal healing and Rag1-/- mice given
      an isotype control antibody developed severe colitis. In contrast, FcgammaR-/
      Rag1-/- mice were refractory to the effects of anti-TNF: their histological
      colitis scores were as severe as those from FcgammaR-/-Rag1-/- mice given a
      control antibody. Colons from Rag1-/- mice that received anti-TNF had an
      increased number of CD206+ macrophages compared with Rag1-/- mice given control
      antibody; in FcgammaR-/-Rag1-/- mice given anti-TNF these numbers were as low as
      FcgammaR-/-Rag1-/- given the control antibody. In human PBMCs, anti-TNF increased
      the number of CD206+ macrophages: this required expression of FcgammaRIIIa;
      numbers of these cells were reduced in PBMCs with the low-affinity FcgammaRIIIa
      158F genotype. A hypo-fucosylated form of adalimumab bound human FcgammaRIIIa
      with a higher affinity than control adalimumab. When hypo-fucosylated adalimumab
      was added to PBMCs, a larger number of CD206+ macrophages formed and T-cell
      proliferation was reduced, compared with addition of a control adalimumab. Hypo
      fucosylated adalimumab increased the number of CD206+ macrophages in PMBCs that
      expressed the low-affinity FcgammaRIIIa. In mice with colitis, hypo-fucosylated
      anti-TNF significantly increased the number of CD206+ macrophages in the colon
      compared with control anti-TNF and was more effective in reducing colitis
      severity as measured by histology. CONCLUSIONS: In a study of the in vitro and in
      vivo mechanisms of anti-TNF, we found FcgammaR engagement by anti-TNF to be
      required for reduction of colitis in mice and development of CD206+ macrophages.
      A hypo-fucosylated form of anti-TNF binds FcgammaRIIIa with higher affinity and
      induces development of CD206+ macrophages in human PBMCs, especially PBMCs that
      express low-affinity FcgammaRIIIa. Hypo-fucosylated anti-TNF might be more
      effective in patients with inflammatory bowel disease.

PMID- 28756236
TI  - Accuracy estimation of an indirect ELISA for the detection of West Nile Virus
      antibodies in wild birds using a latent class model.
AB  - West Nile virus (WNV) and Usutu virus (USUV), genus Flavivirus, are members of
      the Japanese encephalitis virus antigenic complex, and are maintained primarily
      in an enzootic cycle between mosquitoes and birds. WNV is zoonotic, and poses a
      threat to public health, especially in relation to blood transfusion.
      Serosurveillance of wild birds is suitable for early detection of WNV
      circulation, although concerns remain to be addressed as regards i) the type of
      test used, whether ELISA, virus neutralization test (VNT), plaque reduction
      neutralization test (PRNT), ii) the reagents (antigens, revealing antibodies),
      iii) the different bird species involved, and iv) potential cross-reactions with
      other Flaviviruses, such as USUV. The authors developed an indirect IgG ELISA
      with pan-avian specificity using EDIII protein as antigen and a monoclonal
      antibody (mAb 1A3) with broad reactivity for avian IgG. A total of 140 serum
      samples were collected from juvenile European magpies (Pica pica) in areas where
      both WNV and USUV were co-circulating. The samples were then tested using this in
      house ELISA and VNT in parallel. Estimation of test accuracy was performed using
      different Bayesian two latent class models. At a cut-off set at an optical
      density percentage (OD%) of 15, the ELISA showed a posterior median of diagnostic
      sensitivity (DSe) of 88% (95%PCI: 73-99%) and a diagnostic specificity (DSp) of
      86% (95%PCI: 68-99%). At this cut-off, ELISA and VNT (cut-off 1/10) performances
      were comparable: DSe=91% (95%PCI: 79-99%), and DSp=77% (95%PCI: 59-98%). With the
      cut-off increased to 30 OD%, the ELISA DSe dropped to 78% (95%PCI: 52-99%), and
      the DSp rose to 94% (95%PCI: 83-100%). In field conditions, the cut-off that
      yields the best accuracy for the ELISA appears to correspond to 15 OD%. In areas
      where other Flaviviruses are circulating, however, it might be appropriate to
      raise the cut-off to 30 OD% in order to achieve higher specificity and reduce the
      detection of seropositive birds infected by other Flaviviruses, such as USUV.

PMID- 28756237
TI  - Distinct resting-state functional connections associated with episodic and
      visuospatial memory in older adults.
AB  - Episodic and spatial memory are commonly impaired in ageing and Alzheimer's
      disease. Volumetric and task-based functional magnetic resonance imaging (fMRI)
      studies suggest a preferential involvement of the medial temporal lobe (MTL),
      particularly the hippocampus, in episodic and spatial memory processing. The
      present study examined how these two memory types were related in terms of their
      associated resting-state functional architecture. 3T multiband resting state fMRI
      scans from 497 participants (60-82 years old) of the cross-sectional Whitehall II
      Imaging sub-study were analysed using an unbiased, data-driven network-modelling
      technique (FSLNets). Factor analysis was performed on the cognitive battery; the
      Hopkins Verbal Learning test and Rey-Osterreith Complex Figure test factors were
      used to assess verbal and visuospatial memory respectively. We present a map of
      the macroscopic functional connectome for the Whitehall II Imaging sub-study,
      comprising 58 functionally distinct nodes clustered into five major resting-state
      networks. Within this map we identified distinct functional connections
      associated with verbal and visuospatial memory. Functional anticorrelation
      between the hippocampal formation and the frontal pole was significantly
      associated with better verbal memory in an age-dependent manner. In contrast,
      hippocampus-motor and parietal-motor functional connections were associated with
      visuospatial memory independently of age. These relationships were not driven by
      grey matter volume and were unique to the respective memory domain. Our findings
      provide new insights into current models of brain-behaviour interactions, and
      suggest that while both episodic and visuospatial memory engage MTL nodes of the
      default mode network, the two memory domains differ in terms of the associated
      functional connections between the MTL and other resting-state brain networks.

PMID- 28756239
TI  - Trading of dynamic interaural time and level difference cues and its effect on
      the auditory motion-onset response measured with electroencephalography.
AB  - Interaural time (ITD) and level differences (ILD) constitute the two main cues
      for sound localization in the horizontal plane. Despite extensive research in
      animal models and humans, the mechanism of how these two cues are integrated into
      a unified percept is still far from clear. In this study, our aim was to test
      with human electroencephalography (EEG) whether integration of dynamic ITD and
      ILD cues is reflected in the so-called motion-onset response (MOR), an evoked
      potential elicited by moving sound sources. To this end, ITD and ILD trajectories
      were determined individually by cue trading psychophysics. We then measured EEG
      while subjects were presented with either static click-trains or click-trains
      that contained a dynamic portion at the end. The dynamic part was created by
      combining ITD with ILD either congruently to elicit the percept of a
      right/leftward moving sound, or incongruently to elicit the percept of a static
      sound. In two experiments that differed in the method to derive individual
      dynamic cue trading stimuli, we observed an MOR with at least a change-N1 (cN1)
      component for both the congruent and incongruent conditions at about 160-190 ms
      after motion-onset. A significant change-P2 (cP2) component for both the
      congruent and incongruent ITD/ILD combination was found only in the second
      experiment peaking at about 250 ms after motion onset. In sum, this study shows
      that a sound which - by a combination of counter-balanced ITD and ILD cues -
      induces a static percept can still elicit a motion-onset response, indicative of
      independent ITD and ILD processing at the level of the MOR - a component that has
      been proposed to be, at least partly, generated in non-primary auditory cortex.

PMID- 28756238
TI  - AV-1451 PET imaging of tau pathology in preclinical Alzheimer disease: Defining a
      summary measure.
AB  - Utilizing [18F]-AV-1451 tau positron emission tomography (PET) as an Alzheimer
      disease (AD) biomarker will require identification of brain regions that are most
      important in detecting elevated tau pathology in preclinical AD. Here, we
      utilized an unsupervised learning, data-driven approach to identify brain regions
      whose tau PET is most informative in discriminating low and high levels of [18F]
      AV-1451 binding. 84 cognitively normal participants who had undergone AV-1451 PET
      imaging were used in a sparse k-means clustering with resampling analysis to
      identify the regions most informative in dividing a cognitively normal population
      into high tau and low tau groups. The highest-weighted FreeSurfer regions of
      interest (ROIs) separating these groups were the entorhinal cortex, amygdala,
      lateral occipital cortex, and inferior temporal cortex, and an average SUVR in
      these four ROIs was used as a summary metric for AV-1451 uptake. We propose an AV
      1451 SUVR cut-off of 1.25 to define high tau as described by imaging. This
      spatial distribution of tau PET is a more widespread pattern than that predicted
      by pathological staging schemes. Our data-derived metric was validated first in
      this cognitively normal cohort by correlating with early measures of cognitive
      dysfunction, and with disease progression as measured by beta-amyloid PET
      imaging. We additionally validated this summary metric in a cohort of 13
      Alzheimer disease patients, and showed that this measure correlates with
      cognitive dysfunction and beta-amyloid PET imaging in a diseased population.

PMID- 28756240
TI  - Frequency-specific modulation of connectivity in the ipsilateral sensorimotor
      cortex by different forms of movement initiation.
AB  - A consistent finding in motor EEG research is a bilateral attenuation of
      oscillatory activity over sensorimotor regions close to the onset of an upcoming
      unilateral hand movement. In contrast, little is known about how movement
      initiation affects oscillatory activity, especially in the hemisphere ipsilateral
      to the moving hand. We here investigated the neural mechanisms modulating
      oscillatory activity in the ipsilateral motor cortex prior to movement onset
      under the control of two different initiating networks, namely, Self-initiated
      and Visually-cued actions. During motor preparation, a contralateral
      preponderance of power over sensorimotor cortex (SM) was observed in alpha and
      beta bands during Visually-cued movements, whereas power changes were more
      bilateral during Self-initiated movements. Coherence between ipsilateral SM (iSM)
      and contralateral SM (cSM) in the alpha-band was significantly increased compared
      to the respective baseline values, independent of the context of movement
      initiation. However, this context-independent cSM-iSM coherence modulated the
      power changes in iSM in a context-dependent manner, that is, a stronger cSM-iSM
      coherence correlated with a larger decrease in high-beta power over iSM in the
      Self-initiated condition, in contrast to a smaller decrease in alpha power in the
      Visually-cued condition. In addition, the context-dependent coherence between SMA
      and iSM in the alpha-band and delta-theta-band for the Self-initiated and
      Visually-cued condition, respectively, exhibited a similar context-dependent
      modulation for power changes. Our findings suggest that the initiation of
      regional oscillations over iSM reflects changes in the information flow with the
      contralateral sensorimotor and premotor areas dependent upon the context of
      movement initiation. Importantly, the interaction between regional oscillations
      and network-like oscillatory couplings indicates different frequency-specific
      inhibitory mechanisms that modulate the activity in the ipsilateral sensorimotor
      cortex dependent upon how the movement is initiated.

PMID- 28756242
TI  - Unraveling the Genetics of Transplant-Associated Thrombotic Microangiopathy:
      Lessons to be Learned.

PMID- 28756241
TI  - Rapid cerebrovascular reactivity mapping: Enabling vascular reactivity
      information to be routinely acquired.
AB  - Cerebrovascular reactivity mapping (CVR), using magnetic resonance imaging (MRI)
      and carbon dioxide as a stimulus, provides useful information on how cerebral
      blood vessels react under stress. This information has proven to be useful in the
      study of vascular disorders, dementia and healthy ageing. However, clinical
      adoption of this form of CVR mapping has been hindered by relatively long scan
      durations of 7-12 min. By replacing the conventional block presentation of carbon
      dioxide enriched air with a sinusoidally modulated stimulus, the aim of this
      study was to investigate whether more clinically acceptable scan durations are
      possible. Firstly, the conventional block protocol was compared with a sinusoidal
      protocol of the same duration of 7 min. Estimates of the magnitude of the CVR
      signal (CVR magnitude) were found to be in good agreement between the stimulus
      protocols, but estimates of the relative timing of the CVR response (CVR phase)
      were not. Secondly, data from the sinusoidal protocol was reanalysed using
      decreasing amounts of data in the range 1-6 min. The CVR magnitude was found to
      tolerate this reduction in scan duration better than CVR phase. However, these
      analyses indicate that scan durations in the range of 3-5 min produce robust
      data.

PMID- 28756243
TI  - Cytokine Profiles of Pre-Engraftment Syndrome after Single-Unit Cord Blood
      Transplantation for Adult Patients.
AB  - Clinical manifestation of high-grade fever and skin rash before neutrophil
      engraftment, termed pre-engraftment syndrome (PES) or pre-engraftment immune
      reaction, has been frequently observed after cord blood transplantation (CBT).
      The pathophysiology of PES is poorly understood, but cytokine storm during the
      early phase of CBT is thought to be 1 of the main cause of PES. However, the
      cytokine profiles of PES after CBT are unclear. Therefore, we examined the
      relationship between serum cytokine profiles and PES in 44 adult patients who
      received CBT in our institution between February 2013 and June 2016. Serum levels
      of 21 cytokines, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12p70,
      IL-13, IL-17A, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-33, monocyte
      chemoattractant protein-1, IFN-alpha, IFN-gamma, and TNF-alpha, were measured by
      multiplex bead assays using a flow cytometer. The median time until the absolute
      neutrophil count was >.5 * 109/L was 21 days (range, 15 to 41 days). The
      cumulative incidence of PES was 79.6% (95% confidence interval, 63.3% to 88.5%)
      at 60 days after CBT. Serum levels of IL-5 (P = .009) and IL-6 (P = .01) at 2
      weeks were significantly higher in patients who developed PES compared with those
      who did not develop PES. The conversion from naive to effector or central memory
      phenotype of T cells was observed in PES. These data indicate that elevations of
      IL-5 and IL-6 around the time of clinical manifestation may be possible
      biomarkers for PES after CBT.

PMID- 28756244
TI  - High frequency of Bob1lo T follicular helper cells in florid reactive follicular
      hyperplasia.
AB  - Florid reactive follicular hyperplasia (FRFH), which is characterized by large
      germinal centers (GCs) within normal lymphoid follicles, is often observed in
      benign lesions of lymph nodes and other tissues. Because of the histologic
      similarity of FRFH to tumorous lesions such as follicular lymphoma, careful
      pathological examination is required to evaluate such lesions; however, little is
      known about the mechanism underlying the development of FRFH. In this study, we
      investigated T follicular helper (Tfh) cells in hyperplastic tonsils of patients
      with obstructive sleep apnea syndrome (OSA), which frequently exhibits typical
      FRFH. When we analyzed tonsils of OSA and recurrent tonsillitis (RT) as a
      control, tonsils of OSA were found to harbor Tfh cells with a nearly 3-fold
      higher ratio in total CD4+ T cells than that in tonsils of RT. Further analysis
      showed that, in comparison to Tfh cells of RT tonsils, Tfh cells of OSA tonsils
      were relatively tolerant to CD3-mediated activation-induced cell death (AICD) and
      also expressed lower levels of a Bob1 transcription coactivator and IL-4, which
      fosters the development of GC-B cells. Given that Bob1 controls the proliferative
      activity in response to CD3 stimulation and has been suggested to have a role in
      the production of IL-4 in Tfh cells, the unique structure of FRFH is possibly
      associated with the function of Bob1lo Tfh cells.

PMID- 28756245
TI  - Understanding variation in migratory movements: A mechanistic approach.
AB  - Spatial and temporal fluctuations in resource availability have led to the
      evolution of varied migration patterns. In order to appropriately time movements
      in relation to resources, environmental cues are used to provide proximate
      information for timing and the endocrine system serves to integrate these
      external cues and behavioral and physiological responses. Yet, the regulatory
      mechanisms underlying migratory timing have rarely been compared across a broad
      range of migratory patterns. First, we offer an updated nomenclature of migration
      using a mechanistic perspective to clarify terminology describing migratory types
      in relation to ecology, behavior and endocrinology. We divide migratory patterns
      into three types: obligate, nomadic, and fugitive. Obligate migration is
      characterized by regular and directed annual movements between locations, most
      commonly for breeding and overwintering, where resources are predictable and
      sufficient. Nomadic migrations occur less predictably than do obligate migrations
      as animals make use of potentially rich but ephemeral resources that occur
      unpredictably in space or time. Fugitive migrations move animals away from an
      area in response to severe disruption of environmental conditions and occur as
      part of an emergency life history stage. We also consider partially migratory
      populations, which include a mix of sedentary and migratory individuals; the
      movement patterns of partial migrants are expected to fall into one of the three
      types above. For these various forms of migration, we review our understanding of
      the environmental cues and endocrine mechanisms that underlie the expression of a
      migratory state. Several common hormonal mechanisms exist across the varied
      migratory forms, but there are also important areas where further investigations
      are needed in order to gain broad insight into the origin of movements and the
      diversity of migratory patterns. We propose that taking a comparative approach
      across the migratory types that considers endocrine mechanisms will advance a new
      understanding of migration biology.

PMID- 28756247
TI  - AuTom: A novel automatic platform for electron tomography reconstruction.
AB  - We have developed a software package towards automatic electron tomography (ET):
      Automatic Tomography (AuTom). The presented package has the following
      characteristics: accurate alignment modules for marker-free datasets containing
      substantial biological structures; fully automatic alignment modules for datasets
      with fiducial markers; wide coverage of reconstruction methods including a new
      iterative method based on the compressed-sensing theory that suppresses the
      "missing wedge" effect; and multi-platform acceleration solutions that support
      faster iterative algebraic reconstruction. AuTom aims to achieve fully automatic
      alignment and reconstruction for electron tomography and has already been
      successful for a variety of datasets. AuTom also offers user-friendly interface
      and auxiliary designs for file management and workflow management, in which
      fiducial marker-based datasets and marker-free datasets are addressed with
      totally different subprocesses. With all of these features, AuTom can serve as a
      convenient and effective tool for processing in electron tomography.

PMID- 28756248
TI  - Do Trials of Resistance Training to Improve Mobility After Stroke Adhere to the
      American College of Sports Medicine Guidelines? A Systematic Review.
AB  - OBJECTIVE: To determine whether resistance training to improve mobility outcomes
      after stroke adheres to the American College of Sports Medicine (ACSM)
      guidelines, and whether adherence was associated with better outcomes. DATA
      SOURCES: Online databases searched from 1975 to October 30, 2016. STUDY
      SELECTION: Randomized controlled trials examining the effectiveness of lower limb
      strength training on mobility outcomes in adult participants with stroke. DATA
      EXTRACTION: Two independent reviewers completed data extraction. Quality of
      trials was determined using the Cochrane Risk of Bias Tool. Trials were scored
      based on their protocol's adherence to 8 ACSM recommendations. To determine if a
      relation existed between total adherence score and effect size, Spearman rho was
      calculated, and between individual recommendations and effect size, Mann-Whitney
      U or Kruskal-Wallis tests were used. DATA SYNTHESIS: Thirty-nine trials met the
      inclusion criteria, and 34 were scored on their adherence to the guidelines.
      Adherence was high for frequency of training (100% of studies), but few trials
      adhered to the guidelines for intensity (32%), specificity (24%), and training
      pattern (3%). Based on the small number of studies that could be included in
      pooled analysis (n=12), there was no relation between overall adherence and
      effect size (Spearman rho=-.39, P=.21). CONCLUSIONS: Adherence to the ACSM
      guidelines for resistance training after stroke varied widely. Future trials
      should ensure strength training protocols adhere more closely to the guidelines,
      to ensure their effectiveness in stroke can be accurately determined.

PMID- 28756249
TI  - FIM-Minimum Data Set Motor Item Bank: Short Forms Development and Precision
      Comparison in Veterans.
AB  - OBJECTIVE: To improve the practical use of the short forms (SFs) developed from
      the item bank, we compared the measurement precision of the 4- and 8-item SFs
      generated from a motor item bank composed of the FIM and the Minimum Data Set
      (MDS). DESIGN: The FIM-MDS motor item bank allowed scores generated from
      different instruments to be co-calibrated. The 4- and 8-item SFs were developed
      based on Rasch analysis procedures. This article compared person strata,
      ceiling/floor effects, and test SE plots for each administration form and
      examined 95% confidence interval error bands of anchored person measures with the
      corresponding SFs. We used 0.3 SE as a criterion to reflect a reliability level
      of .90. SETTING: Veterans' inpatient rehabilitation facilities and community
      living centers. PARTICIPANTS: Veterans (N=2500) who had both FIM and the MDS data
      within 6 days during 2008 through 2010. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Four- and 8-item SFs of FIM, MDS, and FIM-MDS motor item bank.
      RESULTS: Six SFs were generated with 4 and 8 items across a range of difficulty
      levels from the FIM-MDS motor item bank. The three 8-item SFs all had higher
      correlations with the item bank (r=.82-.95), higher person strata, and less test
      error than the corresponding 4-item SFs (r=.80-.90). The three 4-item SFs did not
      meet the criteria of SE <0.3 for any theta values. CONCLUSIONS: Eight-item SFs
      could improve clinical use of the item bank composed of existing instruments
      across the continuum of care in veterans. We also found that the number of items,
      not test specificity, determines the precision of the instrument.

PMID- 28756250
TI  - Vaspin suppresses cytokine-induced inflammation in 3T3-L1 adipocytes via
      inhibition of NFkappaB pathway.
AB  - Vaspin expression is increased in white adipose tissue (WAT) of diet-induced
      obese mice and rats and is supposed to compensate HFD-induced inflammatory
      processes and insulin resistance in adipose tissue by counteracting pro
      inflammatory gene expression in obesity. Multiple studies have also demonstrated
      strong anti-inflammatory effects in vascular and skin cells. Here, we used vaspin
      treated 3T3-L1 murine adipocytes as well as 3T3-L1 cells with stable vaspin
      expression to investigate the effect of exogenous and endogenous vaspin on
      inflammatory processes and insulin signaling in adipocytes. Our stably
      transfected cells secreted significant amounts of vaspin which was in the
      physiological range of ~0.5 ng/ml in cell supernatants. Adipocyte differentiation
      was not affected by vaspin as expression of adipogenic marker genes as well as
      lipid accumulation after full differentiation was similar to control cells. We
      found that IL-1beta induced expression and secretion of pro-inflammatory
      cytokines, such as IL-6, MCP1 and TNFalpha was significantly blunted in vaspin
      expressing 3T3-L1 cells. Treatment of 3T3-L1 cells with exogenous vaspin resulted
      in reduced cytokine-induced activation of the intracellular and pro-inflammatory
      NFkappaB signaling cascades (IKKalpha/beta, IkappaB and NFkappaB). Moreover,
      endogenous vaspin positively affected insulin signaling by increasing insulin
      stimulated phosphorylation of the key mediator protein kinase B (AKT). Together,
      we demonstrate anti-inflammatory effects of vaspin in 3T3-L1 adipocytes as well
      as increased insulin signaling by endogenous expression or exogenous treatment.
      The results provide evidence for potent anti-inflammatory action of vaspin not
      only in vascular cells but also in adipose tissue.

PMID- 28756246
TI  - Inherited mitochondrial genomic instability and chemical exposures.
AB  - There are approximately 1500 proteins that are needed for mitochondrial structure
      and function, most of which are encoded in the nuclear genome (Calvo et al.,
      2006). Each mitochondrion has its own genome (mtDNA), which in humans encodes 13
      polypeptides, 22 tRNAs and 2 rRNAs required for oxidative phosphorylation. The
      mitochondrial genome of humans and most vertebrates is approximately 16.5kbp,
      double-stranded, circular, with few non-coding bases. Thus, maintaining mtDNA
      stability, that is, the ability of the cell to maintain adequate levels of mtDNA
      template for oxidative phosphorylation is essential and can be impacted by the
      level of mtDNA mutation currently within the cell or mitochondrion, but also from
      errors made during normal mtDNA replication, defects in mitochondrial quality
      control mechanisms, and exacerbated by exposures to exogenous and/or endogenous
      genotoxic agents. In this review, we expand on the origins and consequences of
      mtDNA instability, the current state of research regarding the mechanisms by
      which mtDNA instability can be overcome by cellular and chemical interventions,
      and the future of research and treatments for mtDNA instability.

PMID- 28756251
TI  - Linking hydrogen-enhanced rice aluminum tolerance with the reestablishment of
      GA/ABA balance and miRNA-modulated gene expression: A case study on germination.
AB  - Although previous results showed that exogenous hydrogen (H2) alleviated aluminum
      (Al) toxicity, the detailed mechanism remains unclear. Here, we reported that the
      exposure of germinating rice seeds to Al triggered H2 production, followed by a
      decrease of GA/ABA ratio and seed germination inhibition. Compared to inert gas
      (argon), H2 pretreatment not only strengthened H2 production and alleviated Al
      induced germination inhibition, but also partially reestablished the balance
      between GA and ABA. By contrast, a GA biosynthesis inhibitor paclobutrazol (PAC)
      could block the H2-alleviated germination inhibition. The expression of GA
      biosynthesis genes (GA20ox1 and GA20ox2) and ABA catabolism genes (ABA8ox1 and
      ABA8ox2), was also induced by H2. Above results indicated that GA/ABA might be
      partially involved in H2 responses. Subsequent results revealed that compared
      with Al alone, transcripts of miR398a and miR159a were decreased by H2, and
      expression levels of their target genes OsSOD2 and OsGAMYB were up-regulated.
      Whereas, miR528 and miR160a transcripts were increased differentially, and
      contrasting tendencies were observed in the changes of their target genes (OsAO
      and OsARF10). The transcripts of Al-tolerant gene OsSTAR1/OsSTAR2 and OsFRDL4
      were up-regulated. Above results were consistent with the anti-oxidant defense,
      decreased Al accumulation, and enhanced citrate efflux. Together, our results
      provided insight into the mechanism underlying H2-triggered Al tolerance in
      plants.

PMID- 28756252
TI  - Potential use of lime combined with additives on (im)mobilization and
      phytoavailability of heavy metals from Pb/Zn smelter contaminated soils.
AB  - This explorative study was aimed to assess the efficiency of lime alone and in
      combined with additives to immobilize Pb, Cd, Cu and Zn in soil and reduce their
      phytoavailability for plant. A greenhouse pot experiment was performed by using
      low and heavily contaminated top soils viz. Tongguan contaminated (TG-C);
      Fengxian heavily contaminated (FX-HC) and Fengxian low contaminated (FX-LC). The
      contaminated soils were treated with lime (L) alone and in combined with Ca
      bentonite (CB), Tobacco biochar (TB) and Zeolite (Z) at 1% and cultivated by
      Chinese cabbage (Brassica campestris L). Results revealed that all amendments (p<
      0.05) significantly reduced the DTPA-extractable Pb 97.33, Cd 68.06 and Cu 91.11%
      with L+TB, L+CB, L+Z in FX-LC soil and Zn 87.12% respectively, with L+CB into TG
      C soil. Consequently, the application of lime alone and in combined with
      additives were drastically decreased the dry biomass yield of Brassica campestris
      L. as compared with control. Thus, these feasible amendments potentially maximum
      reduced the uptake by plant shoots upto Pb 53.47 and Zn 67.93% with L+Z and L+TB
      in FX-LC soil, while Cd 68.58 and Cu 60.29% with L+TB, L+CB in TG-C soil but Cu
      uptake in plant shoot was observed 27.26% and 30.17% amended with L+TB and L+Z in
      FX-HC and FX-LC soils. On the other hand, these amendments were effectively
      reduced the potentially toxic metals (PTMs) in roots upto Pb77.77% L alone in FX
      HC, Cd 96.76% with L+TB in TG-C, while, Cu 66.70 and Zn 60.18% with L+Z in FX-LC.
      Meanwhile, all amendments were responsible for increasing soil pH and CEC but
      decreased soils EC level. Based on this result, these feasible soil amendments
      were recommended for long term-study under field condition to see the response of
      another hyper accumulator crop.

PMID- 28756253
TI  - Environmental behavior and eco-toxicity of xylene in aquatic environments: A
      review.
AB  - With the demand for chemicals and fuels increasing continuously, the occurrence
      of accidental leakage poses great risks to the aquatic environment. Xylene, a
      hazardous and noxious substance, has been major concerns with regard to
      heterogeneity and eco-toxicity towards aquatic organisms. This review focused on
      the ecotoxicological hazards of m-, o-, and p-xylene, as well as mixed xylene, on
      aquatic organisms. The mechanism of action of xylenes was also demonstrated in
      details. The purpose of this review was to further understand transfer and
      diffusion of toxicity on marine and freshwater organisms of xylene in the aquatic
      environment. Another aim was to screen sensitive biomarkers which were suitable
      for ecotoxicological assessment and monitoring in an aquatic system.

PMID- 28756254
TI  - Evaluation of chlorpyrifos effects, alone and combined with lipopolysaccharide
      stress, on DNA integrity and immune responses of the three-spined stickleback,
      Gasterosteus aculeatus.
AB  - Organism immune defences might be weakened by pollutants, largely detected in
      aquatic ecosystems, leading to the facilitation for opportunistic pathogens to
      infect organisms. In this context, destabilization of fish non-specific immune
      parameters and erythrocyte DNA integrity was tested, on a model fish species, the
      three-spined stickleback (Gasterosteus aculeatus), after exposure to chlorpyrifos
      (CPF). Alone, pesticide exposure induced a genotoxic potential (chlorpyrifos at
      1.75 and 0.88ug/L) in addition to a decrease in phagocytosis capacity and a
      stimulation of respiratory burst. Then, to mimic pathogenic infection, fish
      exposure to chlorpyrifos was combined with lipopolysaccharides (LPS) stress. In
      this second experiment, an increase of DNA damage was observed in fish exposed to
      a lower concentration of chlorpyrifos and LPS. Moreover, at the higher
      concentration of chlorpyrifos, an early destabilization of innate immunity was
      observed as suggested by the absence of an increase of lysosomal presence in fish
      injected with LPS. This study highlighted the usefulness of stress on stress
      responses to better understand the impact of contaminants on the organism's
      health.

PMID- 28756255
TI  - Microwave assisted solid phase extraction for separation preconcentration
      sulfamethoxazole in wastewater using tyre based activated carbon as solid phase
      material prior to spectrophotometric determination.
AB  - This work was chiefly encouraged by the continuous consumption of antibiotics
      which eventually pose harmful effects on animals and human beings when present in
      water systems. In this study, the activated carbon (AC) was used as a solid phase
      material for the removal of sulfamethoxazole (SMX) in wastewater samples. The
      microwave assisted solid phase extraction (MASPE) as a sample extraction method
      was employed to better extract SMX in water samples and finally the analysis of
      SMX was done by the UV-Vis spectrophotometer. The microwave assisted solid phase
      extraction method was optimized using a two-level fractional factorial design by
      evaluating parameters such as pH, mass of adsorbent (MA), extraction time (ET),
      eluent ratio (ER) and microwave power (MP). Under optimized conditions, the limit
      of detection (LOD) and limit of quantification (LOQ) were 0.5MUgL-1 and 1.7MUgL
      1, respectively, and intraday and interday precision expressed in terms of
      relative standard deviation were >6%.The maximum adsorption capacity was 138mgg-1
      for SMX and the adsorbent could be reused eight times. Lastly, the MASPE method
      was applied for the removal of SMX in wastewater samples collected from a
      domestic wastewater treatment plant (WWTP) and river water.

PMID- 28756256
TI  - Optoelectronic performance comparison of new thiophene linked benzimidazole
      conjugates with diverse substitution patterns.
AB  - In an approach to develop efficient organic optoelectronic devices to be used in
      light-driven systems, a series of three thiophene linked benzimidazole conjugates
      were synthesized and characterized. The combination of two thiophene rings to a
      benzimidazole core decorated with different functional groups (such as OCH3,
      N(CH3)2, CF3) resulted in donor-acceptor type molecular scaffold. The effect of
      the electronic behavior of the substituents on the optical, electrochemical,
      morphological and electron/hole transporting properties of the dyes were
      systematically investigated. DTBI2 dye exhibited distinct absorption properties
      among the other studied dyes because N,N-dimethylamino group initiated
      intramolecular charge transfer (ICT) process in the studied solvents. In solid
      state, the dyes exhibit peaks extending up to 600nm. Depending on the solvent
      polarities, dyes show significant wavelength changes on their fluorescence
      emission spectra in the excited states. Morphological parameters of the thin
      films spin-coated from CHCl3 solution were investigated by using AFM instrument;
      furthermore photovoltaic responses are reported, even though photovoltaic
      performances of the fabricated solar cells with different configurations are
      quite low.

PMID- 28756257
TI  - Quantum mechanical and spectroscopic (FT-IR, FT-Raman) study, NBO analysis, HOMO
      LUMO, first order hyperpolarizability and molecular docking study of methyl[(3R)
      3-(2-methylphenoxy)-3-phenylpropyl]amine by density functional method.
AB  - Quantum chemical techniques such as density functional theory (DFT) have become a
      powerful tool in the investigation of the molecular structure and vibrational
      spectrum and are finding increasing use in application related to biological
      systems. The Fourier transform infrared (FT-IR) and Fourier transform Raman (FT
      Raman) techniques are employed to characterize the title compound. The
      vibrational frequencies were obtained by DFT/B3LYP calculations with 6-31G(d,p)
      and 6-311++G(d,p) as basis sets. The geometry of the title compound was
      optimized. The vibrational assignments and the calculation of Potential Energy
      Distribution (PED) were carried out using the Vibrational Energy Distribution
      Analysis (VEDA) software. Molecular electrostatic potential was calculated for
      the title compound to predict the reactive sites for electrophilic and
      nucleophilic attack. In addition, the first-order hyperpolarizability, HOMO and
      LUMO energies, Fukui function and NBO were computed. The thermodynamic properties
      of the title compound were calculated at different temperatures, revealing the
      correlations between heat capacity (C), entropy (S) and enthalpy changes (H) with
      temperatures. Molecular docking studies were also conducted as part of this
      study. The paper further explains the experimental results which are in line with
      the theoretical calculations and provide optimistic evidence through molecular
      docking that the title compound can act as a good antidepressant. It also
      provides sufficient justification for the title compound to be selected as a good
      candidate for further studies related to NLO properties.

PMID- 28756258
TI  - FT-IR and FT-Raman spectra of 5-chlorocytosine: Solid state simulation and
      tautomerism. Effect of the chlorine substitution in the Watson-Crick base pair 5
      chlorodeoxycytidine-deoxyguanosine.
AB  - The laser Raman and IR spectra of 5-chlorocytosine have been recorded and
      accurately assigned in the solid state using Density functional calculations
      (DFT) together with the linear scaling equation procedure (LSE) and the solid
      state simulation of the crystal unit cell through a tetramer form. These results
      remarkably improve those reported previously by other authors. Several new
      scaling equations were proposed to be used in related molecules. The six main
      tautomers of the biomolecule 5-chlorocytosine were determined and optimized at
      the MP2 and CCSD levels, using different basis sets. The relative stabilities
      were compared with those obtained in cytosine and their 5-halo derivatives.
      Several relationships between energies, geometric parameters and NBO atomic
      charges were established. The effect of the chlorine substitution in the fifth
      position was evaluated through the stability of the Watson-Crick (WC) base pair
      of 5-chlorodeoxycytidine with deoxyguanosine, and through their vibrational
      spectra.

PMID- 28756259
TI  - Detection of triterpene acids distribution in loquat (Eriobotrya japonica) leaf
      using hyperspectral imaging.
AB  - Hyperspectral images (431-962nm) and partial least squares (PLS) were used to
      detect the distribution of triterpene acids within loquat (Eriobotrya japonica)
      leaves. 72 fresh loquat leaves in the young group, mature group and old group
      were collected for hyperspectral imaging; and triterpene acids content of the
      loquat leaves was analyzed using high performance liquid chromatography (HPLC).
      Then the spectral data of loquat leaf hyperspectral images and the triterpene
      acids content were employed to build calibration models. After spectra pre
      processing and wavelength selection, an optimum calibration model (Rp=0.8473,
      RMSEP=2.61mg/g) for predicting triterpene acids was obtained by synergy interval
      partial least squares (siPLS). Finally, spectral data of each pixel in the loquat
      leaf hyperspectral image were extracted and substituted into the optimum
      calibration model to predict triterpene acids content of each pixel. Therefore,
      the distribution map of triterpene acids content was obtained. As shown in the
      distribution map, triterpene acids are accumulated mainly in the leaf mesophyll
      regions near the main veins, and triterpene acids concentration of young group is
      less than that of mature and old groups. This study showed that hyperspectral
      imaging is suitable to determine the distribution of active constituent content
      in medical herbs in a rapid and non-invasive manner.

PMID- 28756260
TI  - Molecular structures, spectroscopic (FT-IR, NMR, UV) studies, NBO analysis and
      NLO properties for tautomeric forms of 1,3-dimethyl-5-(phenylazo)-6-aminouracil
      by density functional method.
AB  - The equilibrium geometry, nuclear magnetic resonance (NMR) and UV-Vis analysis,
      and vibrational frequencies for the azo and hydrazone isomers of 1,3-dimethyl-5
      (phenylazo)-6-aminouracil have been performed using density functional theory
      (DFT/B3LYP) method with 6-311G(d,p) basis set. A detailed interpretation of the
      vibrational spectra has been made on the basis of the calculated potential energy
      distribution (PED) obtained from the Vibrational Energy Distribution Analysis
      (VEDA4) program. The 1H NMR chemical shifts with respect to TMS were calculated
      by the gauge independent atomic orbital (GIAO) method and compared with the
      experimental data. Stability of the molecule arising from hyper conjugative
      interactions, charge delocalization has been analyzed using natural bond orbital
      (NBO) analysis. Using the TD-DFT method, electronic absorption spectra in CHCl3
      solvent of the title compound have been predicted, and good agreement is
      determined with the experimental one. The NLO properties such as mean
      polarizability (?alpha?), the anisotropy of the polarizability (?Deltaalpha?) and
      the mean first-order hyperpolarizability (?beta?) were computed by using finite
      field method. The computed values of MU, alpha and beta for the azo and hydrazone
      forms of the title molecule are 5.4717 and 3.8905 D, 2.7773*10-23 and 2.7598*10
      23esu, and 3.4499*10-30 and 6.8504*10-30esu, respectively. The high beta values
      and non-zero values of MU indicate that the title compound might be a good
      candidate for NLO material.

PMID- 28756261
TI  - Spectroscopic and DFT studies of bis-3-hydroxypyridinium and bis-3
      hydroxymethylpyridinium dibromides with tetramethylene linker.
AB  - Experimental and theoretical IR, Raman, UV-Vis, 1H and 13C NMR spectra of 1,4
      di(3-hydroxypyridinium)butane dibromide and 1,4-di(3
      hydroxymethylpyridinium)butane dibromide were obtained and analyzed. Optimized
      geometrical structures of the studied compounds were calculated by B3LYP method
      using 6-311++G(d,p) basis set and employed to determine the theoretical
      wavenumbers and intensities of IR and Raman spectra. The frequency assignments
      were supported by the potential energy distribution (PED) analysis. The
      significant role of the intermolecular interactions and the hydrogen bond was
      revealed on the basis of IR spectra. The calculated GIAO/B3LYP/6-311++G(d,p)
      isotropic magnetic shielding constants were used to predict the 1H and 13C
      chemical shifts for the optimized structures. Accuracy of the prediction of 1H
      and 13C chemical shifts was significantly improved by a simulation of the solvent
      in calculations. On the basis of UV-Vis spectra the acid-base equilibrium in the
      water solution of 1,4-di(3-hydroxypyridinium)butane dibromide was found.

PMID- 28756262
TI  - Analytical investigation of different mathematical approaches utilizing
      manipulation of ratio spectra.
AB  - This work represents a comparative study of different approaches of manipulating
      ratio spectra, applied on a binary mixture of ciprofloxacin HCl and dexamethasone
      sodium phosphate co-formulated as ear drops. The proposed new spectrophotometric
      methods are: ratio difference spectrophotometric method (RDSM), amplitude center
      method (ACM), first derivative of the ratio spectra (1DD) and mean centering of
      ratio spectra (MCR). The proposed methods were checked using laboratory-prepared
      mixtures and were successfully applied for the analysis of pharmaceutical
      formulation containing the cited drugs. The proposed methods were validated
      according to the ICH guidelines. A comparative study was conducted between those
      methods regarding simplicity, limitations and sensitivity. The obtained results
      were statistically compared with those obtained from the reported HPLC method,
      showing no significant difference with respect to accuracy and precision.

PMID- 28756263
TI  - Synthesis and pharmacological evaluation of benzamide derivatives as potent and
      selective sigma-1 protein ligands.
AB  - A series of novel benzamide-derived compounds was designed, synthesized and
      pharmacologically evaluated. Among all 37 synthesized compounds, two series were
      developed with the modulation of the nature, the position of atoms or groups on
      the benzamide scaffold, but also the nature of the amine group separated from the
      benzamide with 2, 3 or 4 methylene groups. In vitro competition binding assays
      against sigma proteins (sigma-1 S1R and sigma-2 S2R) revealed that most of them
      conferred S2R/S1R selectivity toward without cytotoxic effects on SY5Y cells,
      especially with the first series with compounds 7a-z. Some selected compounds
      were also evaluated for their agonist and antagonist activities on a panel of 40
      receptors. Results showed the importance of the nature and the position with
      halogeno atom on the benzamide scaffold, the length chain but also the
      contribution of the hydrophobic part on the amine group. Among them, compounds
      7i, w, y with Cl, CN or NO2 groups at the 4-position of the benzamide scaffold
      showed excellent affinity for S1R (Ki = 1.2-3.6 nM), selectivity for S2R (Ki up
      to 1400 nM) and high selectivity index (IC50(SY5Y)/Ki(S1R) ratio from 28 000 to
      83 000). Futhermore, these compounds presented an excellent safety profile over
      40 other receptors. These derivatives will be selected for further biological
      investigations.

PMID- 28756264
TI  - Discovery of dehydroabietic acid sulfonamide based derivatives as selective
      matrix metalloproteinases inactivators that inhibit cell migration and
      proliferation.
AB  - A series of dehydroabietic acid (DHAA) dipeptide derivatives containing the
      sulfonamide moiety were designed, synthesized and evaluated for inhibition of
      MMPs as well as the effects of in vitro cell migration. These compounds exhibited
      relatively good inhibition activity against MMPs with IC50 values in low
      micromolar range. A docking study of the most active compound 8k revealed key
      interactions between 8k and MMP-3 in which the sulfonamide moiety and the
      dipeptide group were important for improving activity. It is noteworthy that
      further antitumor activity screening revealed that some compounds exhibited
      better inhibitory activity than the commercial anticancer drug 5-FU. In
      particular, compound 8k appeared to be the most potent compound against the HepG2
      cell line, at least partly, by inhibition of the activity of MMP-3 and apoptosis
      induction. The treatment of HepG2 cells with compound 8k resulted in inhibition
      of in vitro cell migration through wound healing assay and G1 phase of cell cycle
      arrested. In addition, 8k-induced apoptosis was significantly facilitated in
      HepG2 cells. Thus, we conclude that DHAA dipeptide derivatives containing the
      sulfonamide moiety may be the potential MMPs inhibitors with the ability to
      suppress cells migration.

PMID- 28756265
TI  - 4-Aminoquinoline-chalcone/-N-acetylpyrazoline conjugates: Synthesis and
      antiplasmodial evaluation.
AB  - 1H-1,2,3-triazole linked 4-aminoquinoline-chalcone/-N-acetylpyrazoline conjugates
      were synthesized and evaluated against cultured chloroquine (CQ) resistant
      strain. Antiplasmodial activities of the synthesized conjugates revealed
      dependence of activity on the length of the alkyl chain as well as on the
      presence of methoxy substituents on ring A/ring B of the chalcone. The most
      potent and non-cytotoxic conjugate showed comparable antiplasmodial activity with
      that of CQ, with an IC50 value of 53.7 nM.

PMID- 28756266
TI  - Telehealth Protocol to Prevent Readmission Among High-Risk Patients With
      Congestive Heart Failure.
AB  - BACKGROUND: Congestive heart failure is the leading cause of hospital
      readmissions. We aimed to assess adherence to and effectiveness of a telehealth
      protocol designed to prevent hospital admissions for congestive heart failure.
      METHODS: We recruited a random sample of 50 patients with congestive heart
      failure (mean age 61 years) from a managed care organization. We developed a
      telehealth platform allowing for daily, real-time reporting of health status and
      video conferencing. We defined adherence as the percentage of days on which the
      patient completed the daily check-in protocol. To assess efficacy, we compared
      admission and readmission rates between the 6-month intervention period and the
      prior 6 months. Primary outcomes were admissions and readmissions due to
      congestive heart failure, and secondary outcomes were admissions and readmissions
      due to any cause. RESULTS: Forty-eight patients (96%) completed the protocol.
      Approximately half (46%) were at high risk for readmission according to
      standardized measures. Median 120-day adherence was 96% (interquartile range, 92%
      98%), and adherence did not significantly differ across sex, race, age, living
      situation, depression, cognitive ability, or risk for readmission. Approximately
      equal proportions of patients were admitted for all causes during the 6-month
      intervention period versus the comparison period (37% vs 43%; P = .32). Half as
      many patients were admitted for congestive heart failure during the 6-month
      intervention period compared with the comparison period (12% vs 25%; P = .11).
      CONCLUSION: Adherence to this telehealth protocol was excellent and consistent,
      even among high-risk patients. Future research should test the protocol using a
      more rigorous randomized design.

PMID- 28756268
TI  - Case of Tuberculous Pericarditis Mimicking Lupus Carditis.

PMID- 28756267
TI  - The Risk of Major NSAID Toxicity with Celecoxib, Ibuprofen, or Naproxen: A
      Secondary Analysis of the PRECISION Trial.
AB  - BACKGROUND: The relative safety of long-term use of nonsteroidal anti
      inflammatory drugs is unclear. Patients and providers are interested in an
      integrated view of risk . We examined the risk of major nonsteroidal anti
      inflammatory drug toxicity in the PRECISION trial. METHODS: We conducted a post
      hoc analysis of a double-blind, randomized, controlled, multicenter trial
      enrolling 24,081 patients with osteoarthritis or rheumatoid arthritis at moderate
      or high cardiovascular risk. Patients were randomized to receive celecoxib 100 to
      200 mg twice daily, ibuprofen 600 to 800 mg thrice daily, or naproxen 375 to 500
      mg twice daily. All patients were provided with a proton pump inhibitor. The
      outcome was major nonsteroidal anti-inflammatory drug toxicity, including time to
      first occurrence of major adverse cardiovascular events, important
      gastrointestinal events, renal events, and all-cause mortality. RESULTS: During
      follow-up, 4.1% of subjects sustained any major toxicity in the celecoxib arm,
      4.8% in the naproxen arm, and 5.3% in the ibuprofen arm. Analyses adjusted for
      aspirin use and geographic region found that subjects in the naproxen arm had a
      20% (95% CI 4-39) higher risk of major toxicity than celecoxib users and that 38%
      (95% CI 19-59) higher risk. These risks translate into numbers needed to harm of
      135 (95% CI, 72-971) for naproxen and 82 (95% CI, 53-173) for ibuprofen, both
      compared with celecoxib. CONCLUSIONS: Among patients with symptomatic arthritis
      who had moderate to high risk of cardiovascular events, approximately 1 in 20
      experienced a major toxicity over 1 to 2 years. Patients using naproxen or
      ibuprofen experienced significantly higher risk of major toxicity than those
      using celecoxib.

PMID- 28756269
TI  - Slowly Growing Adrenal Mass: A 20-Year Incubation.

PMID- 28756270
TI  - Neuronal territory formation by the atypical cadherins and clustered
      protocadherins.
AB  - Spatial patterns of neuronal connectivity are critical for neural circuit
      function and information processing. For many neuron types, the development of
      stereotyped dendritic and axonal territories involves reiterative contacts
      between neurites and successive re-calibration of branch outgrowth and
      directionality. Here I review emerging roles for members of the atypical
      cadherins (Fmi/Celsrs) and the clustered Protocadherins (Pcdhs) in neurite
      patterning. These cell-surface molecules have shared functions: they engage in
      homophilic recognition and mediate dynamic and contact-dependent interactions to
      establish reproducible and space-filling arborization patterns. As shown in
      genetic and molecular studies, the atypical cadherins and clustered Pcdhs serve
      in multiple contexts and signal diverse actions such as neurite repulsion or
      selective adhesion. In some cell types, they regulate the non-overlapping
      arrangement of branches achieved through homotypic interactions, such as in self
      avoidance or tiling. In others, they promote dendritic complexity through cell
      cell interactions. With critical roles in both the fine-scale arrangement of
      axonal and dendritic branching and the large-scale organization of axon tracts
      and neuronal networks, the atypical cadherins and clustered Pcdhs are key
      regulators of neural circuit assembly and function.

PMID- 28756271
TI  - Antigen-loaded polymeric hybrid micelles elicit strong mucosal and systemic
      immune responses after intranasal administration.
AB  - Increasing attention has been paid to nasal delivery. Subunit vaccines based on
      antigenic proteins or polypeptides offer good safety. However, lack of delivery
      efficiency, particularly for nasal immunization, is a big issue. Here we designed
      a highly tunable polymeric hybrid micelle (PHM) system offering good vaccine
      efficacy after nasal administration. PHMs are formulated from two amphiphilic
      diblock copolymers, polycaprolactone-polyethylenimine (PCL-PEI) and
      polycaprolactone-polyethyleneglycol (PCL-PEG), the ratio of which determines PHM
      physicochemical properties. Citraconic anhydride-modified ovalbumin (Cit-OVA), as
      model antigen, was incorporated into PHMs via electrostatic interaction, giving
      antigen-loaded micelles of around 150nm in size. Their surface characteristics
      which are found closely related to their in vivo kinetics can be modulated by
      adjusting the mass ratio of PCL-PEG and PCL-PEI. PHM/Cit-OVA complexes containing
      PCL-PEI and PCL-PEG in a 1:1 mass ratio induced strong immune responses in nasal
      mucosa and serum in vivo without causing obvious toxicity, and Cit-OVA was
      efficiently internalized by dendritic cells. These results demonstrate the
      promise of this multifunctional polymeric delivery system for nasal vaccination.

PMID- 28756272
TI  - Novel nanosystems for the treatment of ocular inflammation: Current paradigms and
      future research directions.
AB  - Ocular discomforts involve anterior/posterior-segment diseases, symptomatic
      distress and associated inflammations and severe retinal disorders.
      Conventionally, the formulations such as eye drops, eye solutions, eye ointments
      and lotions, etc. were used as modalities to attain relief from such ocular
      discomforts. However, eye allows limited access to these traditional formulations
      due to its unique anatomical structure and dynamic ocular environment and
      therefore calls for improvement in disease intervention. To address these
      challenges, development of nanotechnology based nanomedicines and novel
      nanosystems (liposomes, cubosomes, polymeric and lipidic nanoparticles,
      nanoemulsions, spanlastics and nano micelles) are currently in progress (some of
      them are already marketed such as Eye-logic liposomal eye spray@Naturalife,
      Ireland). Today, it is one of the central concept in designing more accessible
      formulations for deeper segments of the eyes. These nanosystems has largely
      enabled the availability of medicaments at required site in a required
      concentration without inversely affecting the eye tissues; and therefore,
      attaining the excessive considerations from the formulation scientists and
      pharmacologists worldwide. The entrapment of drugs, genes, and proteins inside
      these novel systems is the basis that works at the bio-molecular level bestows
      greater potential to eradicate disease causatives. In this review, we highlighted
      the recent attempts of nanotechnology-based systems for treating and managing
      various ocular ailments. The progress described herein may pave the way to new,
      highly effective and vital ocular nanosystems.

PMID- 28756273
TI  - Back to the Future: Circuit-testing TS & OCD.
AB  - A decade before the rise of optogenetics, the first behavioral "circuit-test" -
      transgenically modulating the output of a genetically-specified brain circuit
      element to examine its effect on behavior - was performed. The behaviors emulated
      in those mice were comorbid tics and compulsions, elicited by a gene borrowed
      from cholera bacteria and tailored to intracellularly neuropotentiate
      glutamatergic somatosensory cortical and limbic output neurons of
      cortico/amygdalo-striato-thalamo-cortical (CSTC) loop circuits. Two decades
      later, cutting-edge chemogenetic and optogenetic methods are again being devoted
      to further characterize the circuits thought to trigger, mediate, aggravate, or
      ameliorate TS & OCD symptoms. These tour de force studies support essential roles
      in tics and compulsions for topographically-parallel corticostriatal and
      amygdalar glutamatergic output neurons; their target dorsal striatal & ventral
      striatal (nucleus accumbens) medium spiny neurons (MSNs) of the direct
      striatothalamic (urge & motor activating) vs. indirect striatopallidal (urge &
      motor suppressing) output pathways; and their converging modulatory dopaminergic
      and histaminergic afferents. Going "back to the future" to circuit-map tics and
      compulsions will give us precision targets for future psychological, drug,
      medtech, and gene therapies; look for "dopamine bypasses" on your next trip in
      the DeLorean.

PMID- 28756274
TI  - Biophysical characterization of the association of histones with single-stranded
      DNA.
AB  - BACKGROUND: Despite the profound current knowledge of the architecture and
      dynamics of nucleosomes, little is known about the structures generated by the
      interaction of histones with single-stranded DNA (ssDNA), which is widely present
      during replication and transcription. METHODS: Non-denaturing gel
      electrophoresis, transmission electron microscopy, atomic force microscopy,
      magnetic tweezers. RESULTS: Histones have a high affinity for ssDNA in 0.15M NaCl
      ionic strength, with an apparent binding constant similar to that calculated for
      their association with double-stranded DNA (dsDNA). The length of DNA (number of
      nucleotides in ssDNA or base pairs in dsDNA) associated with a fixed core histone
      mass is the same for both ssDNA and dsDNA. Although histone-ssDNA complexes show
      a high tendency to aggregate, nucleosome-like structures are formed at
      physiological salt concentrations. Core histones are able to protect ssDNA from
      digestion by micrococcal nuclease, and a shortening of ssDNA occurs upon its
      interaction with histones. The purified (+) strand of a cloned DNA fragment of
      nucleosomal origin has a higher affinity for histones than the purified
      complementary (-) strand. CONCLUSIONS: At physiological ionic strength histones
      have high affinity for ssDNA, possibly associating with it into nucleosome-like
      structures. GENERAL SIGNIFICANCE: In the cell nucleus histones may spontaneously
      interact with ssDNA to facilitate their participation in the replication and
      transcription of chromatin.

PMID- 28756275
TI  - Spectroscopic insights into quadruplexes of five-repeat telomere DNA sequences
      upon G-block damage.
AB  - BACKGROUND: The DNA lesions, resulting from oxidative damage, were shown to
      destabilize human telomere four-repeat quadruplex and to alter its structure.
      Long telomere DNA, as a repetitive sequence, offers, however, other mechanisms of
      dealing with the lesion: extrusion of the damaged repeat into loop or shifting
      the quadruplex position by one repeat. METHODS: Using circular dichroism and UV
      absorption spectroscopy and polyacrylamide electrophoresis, we studied
      consequences of lesions at different positions of the model five-repeat human
      telomere DNA sequences on the structure and stability of their quadruplexes in
      sodium and in potassium. RESULTS: The repeats affected by lesion are
      preferentially positioned as terminal overhangs of the core quadruplex
      structurally similar to the four-repeat one. Forced affecting of the inner
      repeats leads to presence of variety of more parallel folds in potassium. In
      sodium the designed models form mixture of two dominant antiparallel quadruplexes
      whose population varies with the position of the affected repeat. The shapes of
      quadruplex CD spectra, namely the height of dominant peaks, significantly
      correlate with melting temperatures. CONCLUSION: Lesion in one guanine tract of a
      more than four repeats long human telomere DNA sequence may cause re-positioning
      of its quadruplex arrangement associated with a shift of the structure to less
      common quadruplex conformations. The type of the quadruplex depends on the loop
      position and external conditions. GENERAL SIGNIFICANCE: The telomere DNA
      quadruplexes are quite resistant to the effect of point mutations due to the
      telomere DNA repetitive nature, although their structure and, consequently,
      function might be altered.

PMID- 28756276
TI  - Cryo-electron microscopy for structural analysis of dynamic biological
      macromolecules.
AB  - BACKGROUND: Since the introduction of what became today's standard for cryo
      embedding of biological macromolecules at native conditions more than 30years
      ago, techniques and equipment have been drastically improved and the structure of
      biomolecules can now be studied at near atomic resolution by cryo-electron
      microscopy (cryo-EM) while capturing multiple dynamic states. Here we review the
      recent progress in cryo-EM for structural studies of dynamic biological
      macromolecules. SCOPE OF REVIEW: We provide an overview of the cryo-EM method and
      introduce contemporary studies to investigate biomolecular structure and
      dynamics, including examples from the recent literature. MAJOR CONCLUSIONS: Cryo
      EM is a powerful tool for the investigation of biological macromolecular
      structures including analysis of their dynamics by using advanced image
      processing algorithms. The method has become even more widely applicable with
      present-day single particle analysis and electron tomography. GENERAL
      SIGNIFICANCE: The cryo-EM method can be used to determine the three-dimensional
      structure of biomacromolecules in near native condition at close to atomic
      resolution, and has the potential to reveal conformations of dynamic molecular
      complexes. This article is part of a Special Issue entitled "Biophysical
      Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi
      Kato.

PMID- 28756277
TI  - New carbazole linked 1,2,3-triazoles as highly potent non-sugar alpha-glucosidase
      inhibitors.
AB  - In the present study, a series of new carbazole linked 1H-1,2,3-triazoles (2-27)
      were synthesized via click reaction of N-propargyl-9H-carbazole (1) and azides of
      appropriate acetophenones and heterocycles. Synthesized carbazole triazoles
      including 7, 9, 10, 19, 20, and 23-26 (IC50=0.8+/-0.01-100.8+/-3.6MUM), exhibited
      several folds more potent alpha-glucosidase inhibitory in vitro activity as
      compared to standard drug, acarbose. Compounds 2-5, 7-13, and 17-27 did not show
      any cytotoxicity against 3T3 cell lines, except triazoles 6, and 14-16. Among the
      series, carbazole triazoles 23 (IC50=1.0+/-0.057MUM) and 25 (IC50=0.8+/-0.01MUM)
      were found to be most active, and could serve as an attractive building block in
      the search of new non-sugar derivatives as anti-diabetic agents.

PMID- 28756278
TI  - Effects of dietary weight loss with and without exercise on interstitial matrix
      turnover and tissue inflammation biomarkers in adults with knee osteoarthritis:
      the Intensive Diet and Exercise for Arthritis trial (IDEA).
AB  - OBJECTIVE: To examine the effects of dietary weight loss, with and without
      exercise, on selected soluble biomarkers in overweight and obese older adults
      with symptomatic knee osteoarthritis (OA). DESIGN: Blood samples were analyzed
      from 429 participants in the Intensive Diet and Exercise for Arthritis (IDEA)
      trial randomized to either an 18 month exercise control group (E), weight loss
      diet (D), or D + E. C1M, C2M, C3M and CRPM biomarkers and interleukin-6 (IL-6)
      were quantitated using ELISAs. Radiographic progression was defined as a decrease
      in joint space width of >=0.7 mm. Statistical modeling of group means and
      associations used mixed models adjusted for visit, baseline body mass index
      (BMI), gender, and baseline values of the outcome. RESULTS: Compared to the E
      control group, C1M was significantly lower in the D and D + E groups at both 6
      and 18 months while C3M was significantly lower in D and D + E at 6 months and in
      D + E at 18 months. C2M did not change in any group. Using data from all groups,
      change in C1M (P < 0.0001), C3M (P < 0.0001), as well as CRPM (P = 0.0004) from
      baseline to 18 months was positively associated with change in weight. No marker
      was associated with change in Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) pain or radiographic progression. C3M (P = 0.008)
      and CRPM (P = 0.028) were positively associated with change in WOMAC function.
      Change in IL-6 was positively associated with change in C1M, C3M, and CRPM.
      CONCLUSION: Overweight and obese adults with knee OA who lost weight from diet
      and diet plus exercise reduced serum markers of interstitial matrix turnover and
      inflammation but not type II collagen degradation.

PMID- 28756279
TI  - Association between statin use and consultation or surgery for osteoarthritis of
      the hip or knee: a pooled analysis of four cohort studies.
AB  - OBJECTIVE: Experimental findings and previous observational data have suggested
      lower risk of osteoarthritis (OA) with statin use but results are inconsistent.
      Large-scale studies with a clinically important outcome are needed. Thus, we
      aimed to determine whether statin use is associated with a reduced risk of
      developing clinically-defined hip or knee OA. DESIGN: Pooled analysis based on
      time-to-event analysis of four population-based large cohorts, encompassing in
      total 132,607 persons aged 57-91 years resident in southern and central Sweden.
      We studied the association between statin use and time to consultation or surgery
      for OA of the hip or knee by time-dependent exposure analysis and Cox regression.
      RESULTS: During 7.5 years of follow-up, we identified 7468 out- or inpatient
      treated cases of hip or knee OA. Compared with never use, current use of statins
      conferred no overall reduction in the risk of OA with an adjusted pooled hazard
      ratio (HR) of 1.04 (95% confidence intervals [95% CI] 0.99-1.10). We found no
      dose-response relation between duration of current statin use and the risk of OA,
      with similar HRs among patients with less than 1 year of use (HR 1.09; 95% CI
      0.92-1.32) as in patients with use for 3 years or more (HR 1.05; 0.93-1.16).
      Results were comparable in those with low, medium and high dose of current statin
      use, without indications of heterogeneity of study results. CONCLUSION: Statin
      use is not associated with reduced risk of consultation or surgery for OA of the
      hip or knee.

PMID- 28756280
TI  - Engineering of small interfering RNA-loaded lipidoid-poly(DL-lactic-co-glycolic
      acid) hybrid nanoparticles for highly efficient and safe gene silencing: A
      quality by design-based approach.
AB  - Safety and efficacy of therapeutics based on RNA interference, e.g., small
      interfering RNA (siRNA), are dependent on the optimal engineering of the delivery
      technology, which is used for intracellular delivery of siRNA to the cytosol of
      target cells. We investigated the hypothesis that commonly used and poorly
      tolerated cationic lipids might be replaced with more efficacious and safe
      lipidoids as the lipid component of siRNA-loaded lipid-polymer hybrid
      nanoparticles (LPNs) for achieving more efficient gene silencing at lower and
      safer doses. However, formulation design of such a complex formulation is highly
      challenging due to a strong interplay between several contributing factors.
      Hence, critical formulation variables, i.e. the lipidoid content and
      siRNA:lipidoid ratio, were initially identified, followed by a systematic quality
      by-design approach to define the optimal operating space (OOS), eventually
      resulting in the identification of a robust, highly efficacious and safe
      formulation. A 17-run design of experiment with an I-optimal approach was
      performed to systematically assess the effect of selected variables on critical
      quality attributes (CQAs), i.e. physicochemical properties (hydrodynamic size,
      zeta potential, siRNA encapsulation/loading) and the biological performance (in
      vitro gene silencing and cell viability). Model fitting of the obtained data to
      construct predictive models revealed non-linear relationships for all CQAs, which
      can be readily overlooked in one-factor-at-a-time optimization approaches. The
      response surface methodology further enabled the identification of an OOS that
      met the desired quality target product profile. The optimized lipidoid-modified
      LPNs revealed more than 50-fold higher in vitro gene silencing at well-tolerated
      doses and approx. a twofold increase in siRNA loading as compared to reference
      LPNs modified with the commonly used cationic lipid dioleyltrimethylammonium
      propane (DOTAP). Thus, lipidoid-modified LPNs show highly promising prospects for
      efficient and safe intracellular delivery of siRNA.

PMID- 28756281
TI  - Quantifying the mode II critical strain energy release rate of borate bioactive
      glass coatings on Ti6Al4V substrates.
AB  - Bioactive glasses have been used as coatings for biomedical implants because they
      can be formulated to promote osseointegration, antibacterial behavior, bone
      formation, and tissue healing through the incorporation and subsequent release of
      certain ions. However, shear loading on coated implants has been reported to
      cause the delamination and loosening of such coatings. This work uses a recently
      developed fracture mechanics testing methodology to quantify the critical strain
      energy release rate under nearly pure mode II conditions, GIIC, of a series of
      borate-based glass coating/Ti6Al4V alloy substrate systems. Incorporating
      increasing amounts of SrCO3 in the glass composition was found to increase the
      GIIC almost twofold, from 25.3 to 46.9J/m2. The magnitude and distribution of
      residual stresses in the coating were quantified, and it was found that the
      residual stresses in all cases distributed uniformly over the cross section of
      the coating. The crack was driven towards, but not into, the glass/Ti6Al4V
      substrate interface due to the shear loading. This implied that the interface had
      a higher fracture toughness than the coating itself.

PMID- 28756282
TI  - Electrochemical corrosion and bioactivity of Ti-Nb-Sn-hydroxyapatite composites
      fabricated by pulse current activated sintering.
AB  - Ti-Nb-Sn-hydroxyapatite (HA) composites were prepared by mechanical alloying for
      different times (unmilled, 4, 8 and 12h), followed by pulse current activated
      sintering. The effects of the milling time on the electrochemical corrosion
      resistance and bioactivity of the sintered Ti-35Nb-2.5Sn-15HA composites were
      investigated. Potentiodynamic polarization test results indicated that the
      sintered Ti-35Nb-2.5Sn-15HA composites exhibited higher corrosion resistance with
      increasing milling time. The corrosion potential and current of the Ti-35Nb-2.5Sn
      15HA composite sintered by 12h milled powders were - 0.261V and 0.18MUA/cm2,
      respectively, and this sintered composite showed a stable and wide passivation
      region. The hemolysis rate of the sintered Ti-35Nb-2.5Sn-15HA composites reduced
      with increasing milling time and the lowest hemolytic rate of the composites was
      0.87%. In addition, the in vitro cell culture results indicated that the
      composite sintered by 12h milled powders had good biocompatibility. These results
      indicate the significant potential of Ti-35Nb-2.5Sn/xHA composites for biomedical
      implant applications.

PMID- 28756283
TI  - Design and characterization of a hyperelastic tubular soft composite.
AB  - Research in the field of human mobility assistive devices, aiming to reduce the
      metabolic cost of daily activities, is seeing the benefits of the exclusive use
      of passive actuators to store and release energy during the gait cycle. Current
      devices commonly employ either mechanical springs or Pneumatic Artificial Muscles
      as the primary method of passive actuation. The Pneumatic Artificial Muscle has
      proven to be a superior actuation choice for these devices, when compared to its
      alternatives. However, challenges regarding muscle pressure loss and limited
      elongation potential have been identified. This paper presents a hyperelastic
      tubular Soft Composite that replicates the distinctive mechanical behaviour of
      the Pneumatic Artificial Muscle without the need for internal pressurization. The
      proposed Soft Composite solution is achieved by impregnating a prefabricated
      polyethylene terephthalate braided sleeve, held at a high initial fibre angle,
      with a silicone prepolymer. A comprehensive experimental evaluation is achieved
      on numerous prototypes for a variety of customizable design parameters including:
      the initial fibre angle, the silicone stiffness, and the braided sleeve style.
      This research has successfully developed, tested, and validated a novel Soft
      Composite that can achieve the desired nonlinear stiffness and elongation
      potential for optimal use as passive actuation in human mobility assistive
      devices.

PMID- 28756284
TI  - Strain rate dependent hyperelastic stress-stretch behavior of a silica
      nanoparticle reinforced poly (ethylene glycol) diacrylate nanocomposite hydrogel.
AB  - Poly (ethylene glycol) diacrylate (PEGDA) derivatives are important biomedical
      materials. PEGDA based hydrogels have emerged as one of the popular regenerative
      orthopedic materials. This work aims to study the mechanical behavior of a PEGDA
      based silica nanoparticle (NP) reinforced nanocomposite (NC) hydrogel at
      physiological strain rates. The work combines materials fabrication, mechanical
      experiments, mathematical modeling and structural analysis. The strain rate
      dependent stress-stretch behaviors were observed, analyzed and quantified. Visco
      hyperelasticity was identified as the deformation mechanism of the nano
      silica/PEGDA NC hydrogel. NPs showed significant effect on both initial shear
      modulus and viscoelastic materials properties. A structure-based quasi-linear
      viscoelastic (QLV) model was constructed and capable to describe the visco
      hyperelastic stress-stretch behavior of the NC hydrogel. A group of unified
      material parameters was extracted by the model from the stress-stretch curves
      obtained at different strain rates. Visco-hyperelastic behavior of NP/polymer
      interphase was not only identified but also quantified. The work could provide
      guidance to the structural design of next-generation NC hydrogel.

PMID- 28756285
TI  - Longitudinal effects of Parathyroid Hormone treatment on morphological,
      densitometric and mechanical properties of mouse tibia.
AB  - The use of Parathyroid Hormone (PTH) as bone anabolic is limited due to cost
      benefit assessments. Preclinical studies evaluating the effects of PTH on bone
      have reported variable and often contradictory results. Here, we have applied a
      new approach using a combination of in-vivo longitudinal uCT, image processing
      techniques and finite element models to monitor early local changes in the whole
      tibia (divided in 40 compartments) and mechanical properties of female C57BL/6J
      mice treated with PTH 1-34, compared to controls. Compared with standard 3D bone
      morphometric analysis, our new approach allowed detection of much smaller and
      localised changes in bone mineral content (BMC) at very early time points (1 week
      vs 3 weeks with standard methods) and showed that changes do not occur uniformly
      over time and across the anatomical space. Indeed, in the PTH treated mice,
      significant changes in BMC were observed in the medial and posterior sectors of
      the proximal tibia, a week after treatment, and in the medial sector of the tibia
      midshaft region a week later (p < 0.05). By the third week, two thirds of the
      regions showed significantly higher values of BMC (p < 0.05). The effect of PTH
      on bone regional volume is similar to that on BMC, but there is almost no effect
      of PTH on bone tissue mineral density. The differences in estimated mechanical
      properties became significant after three weeks of treatment (p < 0.05). These
      results provide the first evidence of an early and localised PTH effect on murine
      bone, and show that our novel partitioning approach, compared to the standard
      evaluation protocol, allows a more precise quantification of bone changes
      following treatment, which would facilitate preclinical testing of novel mono-
      and/or combination therapies throughout the bone.

PMID- 28756286
TI  - The effect of annealing temperature on the properties of powder metallurgy
      processed Ti-35Nb-2Zr-0.5O alloy.
AB  - Ti-35Nb-2Zr-0.5O (wt%) alloy was prepared via a powder metallurgy process (cold
      isostatic pressing of blended elemental powders and subsequent sintering) with
      the primary aim of using it as a material for bio-applications. Sintered
      specimens were swaged and subsequently the influence of annealing temperature on
      the mechanical and structural properties was studied. Specimens were annealed at
      800, 850, 900, 950, and 1000 degrees C for 0.5h and water quenched. Significant
      changes in microstructure (i.e. precipitate dissolution or grain coarsening) were
      observed in relation to increasing annealing temperature. In correlation with
      those changes, the mechanical properties were also studied. The ultimate tensile
      strength increased from 925MPa (specimen annealed at 800 degrees C) to 990MPa
      (900 degrees C). Also the elongation increased from ~ 13% (800 degrees C) to more
      than 20% (900, 950, and 1000 degrees C).

PMID- 28756287
TI  - Interplay between the gut microbiota and immune responses of ayu (Plecoglossus
      altivelis) during Vibrio anguillarum infection.
AB  - Gut microbiota plays fundamental roles in protection against pathogen invasion.
      However, the mechanism and extent of responses of gut microbiota to pathogenic
      infection are poorly understood. This study investigated the gut bacterial
      communities and immune responses of ayu (Plecoglossus altivelis) upon exposure to
      Vibrio anguillarum. The succession of V. anguillarum infection was evidenced by
      increased expression of immune genes and bacterial loads in ayu tissues, which in
      turn altered the composition and predicted functions of gut bacterial community.
      The dynamics of gut bacterial diversity and evenness were temporally stable in
      control ayu but were reduced in infected subjects, particularly at the late
      stages of infection. Variations in the gut microbiota were significantly
      associated with the expression levels of TNF-alpha (P = 0.019) and IL-1 beta (P =
      0.013). The profiles of certain gut bacterial taxa were indicative of V.
      anguillarum infection. Compared with healthy controls, the ayu infected with V.
      anguillarum possessed less complex, fewer connected, and lower cooperative gut
      bacterial interspecies interaction, coinciding with significant shifts in
      keystone species. These findings imply that V. anguillarum infection
      substantially disrupted the compositions and interspecies interaction of ayu gut
      bacterial community, thereby altering gut microbial-mediated functions and
      inducing host immune responses. This study provides an integrated overview on the
      interaction between the gut microbiota and host immune responses to pathogen
      infection from an ecological perspective.

PMID- 28756288
TI  - Production of RNase III-knockout, auxotrophic Edwardsiella tarda mutant for
      delivery of long double-stranded RNA and evaluation of its immunostimulatory
      potential.
AB  - The artificially synthesized polyinosinic-polycytidylic acid (poly IC) has been
      widely used to induce type I IFN responses in various vertebrates including fish.
      However, as poly IC is too expensive to use in aquaculture, the development of
      another economical long dsRNA producing method is needed to practically use long
      dsRNAs in aquaculture farms for the control of infectious diseases. In the
      present study, to produce long dsRNAs economically, we developed a novel long
      dsRNA production system based on the RNase III gene deleted auxotrophic mutant E.
      tarda (DeltaalrDeltarncDeltaasd E. tarda) and a long dsRNA-producing vector that
      was equipped with two modified lambda phage PR promoters arranged in a head-to
      head fashion. As the present genetically engineered E. tarda cannot live without
      supplementation of d-alanine and DAP, environmental and medicinal risks are
      minimized. Olive flounder (Paralichthys olivaceus) fingerlings administered the
      long dsRNA-producing auxotrophic E. tarda mutant (Deltaalr DeltarncDeltaasd E.
      tarda) showed significantly higher expressions of TLR22, Mx1, and ISG15 genes,
      indicating a potential to increase type I interferon responses.

PMID- 28756289
TI  - Generation of a recombinant viral hemorrhagic septicemia virus (VHSV) expressing
      olive flounder (Paralichthys olivaceus) interferon-gamma and its effects on type
      I interferon response and virulence.
AB  - Rhabdoviruses including viral hemorrhagic septicemia virus (VHSV) are highly
      susceptible to type I interferon (IFN) responses, and IFN-gamma that is belonging
      to the type II IFN has been known to enhance type I IFN responses in mammals. In
      this study, we generated a recombinant VHSV that can express olive flounder IFN
      gamma (rVHSV-A-IFNgamma) using reverse genetics technology, and analyzed the
      effect of rVHSV-A-IFNgamma infection on type I IFN response in Epithelioma
      papulosum cyprini (EPC) cells. Furthermore, the virulence of rVHSV-A-IFNgamma was
      evaluated by infection to olive flounder (Paralichthys olivaceus). Using a
      recombinant VHSV full genome vector in which the olive flounder IFN-gamma ORF was
      inserted between N and P genes, rVHSV-A-IFNgamma was successfully rescued, and
      the recombinant virus was grown well in EPC cells. On the other hand, the growth
      of rVHSV-A-IFNgamma rescued from EPC cells was severely retarded when infected
      into hirame natural embryo (HINAE) cells that were originated from olive
      flounder. These results indicate that the EPC cell's IFN-gamma receptor could not
      bind to olive flounder IFN-gamma, but the species-specific binding of IFN-gamma
      in HINAE cells induced antiviral responses. The expression of Mx1 gene in EPC
      cells infected with rVHSV-A-IFNgamma was not greatly different from cells
      infected with rVHSV-Arfp (a recombinant VHSV harboring red fluorescent protein
      gene between N and P genes of the genome), however, in HINAE cells, rVHSV-A
      IFNgamma infection induced distinctively higher Mx1 gene expression compared to
      other recombinant viruses. These results suggest that olive flounder IFN-gamma
      produced from rVHSV-A-IFNgamma effectively enhanced type I IFN response in HINAE
      cells. In the present study, the lowest mortality of olive flounder fingerlings
      was recorded in the group of fish challenged with rVHSV-A-IFNgamma, suggesting
      that the recombinant VHSV was attenuated by production of IFN-gamma by itself.
      However, although rVHSV-A-IFNgamma induced significantly lower mortality, the
      mortality still reached to 40%. Therefore, to be safely used in the aquaculture
      farms as prophylactic vaccines or immunostmulators, further manipulations that
      can guarantee safety are needed.

PMID- 28756290
TI  - Exploring the association between BDNF Val66Met polymorphism and suicidal
      behavior: Meta-analysis and systematic review.
AB  - Suicide is a serious worldwide health problem of critical consequences. Nowadays
      genetic factors are considered to be an important cause of suicide. The
      association between Val66Met (rs6265) polymorphism of the BDNF gene and suicide
      behavior has been increasingly studied. The aim of this study was to perform a
      meta-analysis in order to unravel the possible association between BDNF gene
      Val66Met polymorphism and suicide behavior. These meta-analysis and systematic
      review were performed using 23 articles that searched for a genetic association
      between Val66Met and suicide behavior, including 4532 cases and 5364 control
      subjects. The association was analyzed following the models: allelic, homozygous,
      heterozygous, dominant and recessive. Also, analyses by ethnicity (Caucasian and
      Asian populations) were done following the same four models. When the overall
      population was evaluated, we found no evidence of association between the
      polymorphism Val66Met of BDNF (rs6265) and suicide behavior (Met vs. Val: OR:
      1.01; 95% CI = 0.92-1.10). However, a significant increased risk was found in the
      subgroup analysis by ethnicity in Caucasian populations (Met-Met vs. Met-Val +
      Val-Val: OR: 1.96; 95% CI = 1.58-2.43) and Asian populations (Val-Val vs. Val-Met
      + Met: OR: 1.36; 95% CI = 1.04-1.78). Our results suggest there is no association
      between the BDNF gene Val66Met (rs6265) and suicide behavior in the overall
      population. However, ethnic differences can be observed and the BDNF Val66Met
      might increase the risk for suicide behavior in Asian and Caucasian populations.
      Further studies with larger samples are necessary in order to have conclusive
      outcomes.

PMID- 28756291
TI  - Learning terms and definitions: Drawing and the role of elaborative encoding.
AB  - Traditionally, students adopt the strategy of taking written notes when attending
      a class or learning from a textbook in educational settings. Informed by previous
      work showing that learning by doing improves memory performance, we examined
      whether drawing to-be-remembered definitions from university textbooks would
      improve later memory, relative to a more typical strategy of rote transcription.
      Participants were asked to either write out the definition, or to draw a picture
      representative of the definition. Results indicated that drawing, relative to
      verbatim writing, conferred a reliable memorial benefit that was robust, even
      when participants' preexisting familiarity with the terms was included as a
      covariate (in Experiment 1) or when the to-be-remembered terms and definitions
      were fictitious, thus removing the influence of familiarity (in Experiment 2). We
      reasoned that drawing likely facilitates retention at least in part because at
      encoding, participants must retain and elaborate upon information regarding the
      meaning of the definition, to translate it into a new form (a picture). This is
      not the case when participants write out the definitions verbatim. In Experiment
      3 we showed that paraphrasing during encoding, which, like drawing and in
      contrast with verbatim writing, requires self-generated elaboration, led to
      memory performance that was comparable to drawing. Taken together, results
      suggest that drawing is a powerful tool which improves memory, and that drawing
      produces a similar level of retention as does paraphrasing. This suggests that
      elaborative encoding plays a critical role in the memorial benefit that drawing
      confers to memory for definitions of academic terms.

PMID- 28756293
TI  - Synthesis of 19-norcalcitriol analogs with alkylidene moieties at C-2 based on
      succinic acid and l-methionine.
AB  - On the basis of the literature data, our previous research work and docking
      experiments, we designed novel 19-norvitamin D compounds having elongated 2
      alkylidene substituents. These 19-norcalcitriol derivatives have attached 2-(3'
      aminopropylidene) substituent in which the nitrogen atom bears acyl residue
      derived from succinic acid and l-methionine. Both compounds were obtained by the
      same synthetic strategy involving Julia coupling of the A-ring ketone with the
      known C/D-ring sulfone. In the obtained 1alpha,25-dihydroxy-19-norvitamin D3
      derivative, the alkylidene substituent at C-2 was further elaborated to the
      desired structures.

PMID- 28756292
TI  - Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms
      of cytotoxic action and effects on angiogenesis in vitro.
AB  - The synthesis and cytotoxic activities determination of new steroidal mono- and
      bis(thiazolidin-4-ones) 4a-f and 5a-f have been performed. Their anticancer
      action was also evaluated in comparison to previously synthesized and reported
      corresponding steroidal thiosemicarbazones. All compounds were obtained as
      stereoisomeric mixtures with different configuration (E or Z) in the hydrazone
      moiety at the C-3 position. After several consecutive crystallizations
      diastereomerically pure major (E)-isomers of mono-thiazolidin-4-ones were
      isolated. The structure and stereochemistry of 2,4-thiazolidinedione,2-[(17
      oxoandrost-4-en-3-ylidene)hydrazone] were confirmed by X-ray analysis. A pathway
      for the formation of thiazolidin-4-one ring was proposed. The steroid
      thiazolidinone derivatives examined in this study exerted selective concentration
      dependent cytotoxic activities on six tested malignant cell lines. Ten out of
      twelve examined compounds exhibited strong cytotoxic effects on K562 cells (IC50
      values from 8.5MUM to 14.9MUM), eight on HeLa cells (IC50 values ranging from
      8.9MUM to 15.1MUM) while against MDA-MB-361 cells six compouds exerted similar or
      even higher cytotoxic action (IC50 values from 12.7MUM to 25.6MUM) than cisplatin
      (21.5MUM) which served as a positive control. Eight of these ten compounds showed
      high selectivity in the cytotoxic action against HeLa and K562 cancer cell lines
      when compared with normal human fibroblasts MRC-5 and normal human PBMC. The
      study of mechanisms of the anticancer activity of the two selected compounds,
      mono- and bis(thiazolidin-4-one) derivatives of 19-norandrost-4-ene-3,17-dione 4a
      and 5a, revealed that both of these compounds induced apoptosis in HeLa cells
      through extrinsic and intrinsic signalling pathways. Treatment of EA.hy926 cells
      with sub-toxic concentrations of these compounds led to the inhibition of cell
      connecting and sprouting, and tube formation. The synthesized compounds exhibited
      poor antioxidant activity.

PMID- 28756294
TI  - Vitamin D, cod liver oil, sunshine, and phototherapy: Safe, effective and
      forgotten tools for treating and curing tuberculosis infections - A comprehensive
      review.
AB  - Tuberculosis remains an epidemic throughout the world, with over 2 billion
      people, or more than one third of the world's population, infected with TB. In
      2015, there were an estimated 10.4 million new cases of tuberculosis, and 1.8
      million deaths, making TB one of the top ten causes of death worldwide.
      Approximately 95% of new TB cases occur in developing countries, where the costs
      of treatment force many patients and their families into poverty. The United
      Nations and the World Health Organization are working to end this global
      epidemic. Historically, cod liver oil in the 1840's, phototherapy in the 1890's,
      sunshine in the 1890's and 1930's, oral vitamin D in doses of 100,000-150,000
      international units a day the 1940's, and injectable vitamin D in the 1940's were
      all shown to be able to safely treat tuberculosis. However, for reasons that are
      unclear, these treatments are no longer being used to treat tuberculosis. We will
      review several reports that documented the clinical efficacy of these seemingly
      disparate treatments in treating tuberculosis. Taken together, however, these
      reports show the consistent efficacy of vitamin D in treating tuberculosis
      infections, regardless of whether the vitamin D was produced in the skin from the
      effects of phototherapy or sunshine, taken orally as a pill or in cod-liver oil,
      or put into solution and injected directly into the body. We will discuss how
      vitamin D, through its action as a steroid hormone that regulates gene
      transcription in cells and tissues throughout the body, enables the body to
      eradicate TB by stimulating the formation of a natural antibiotic in white blood
      cells, the mechanism of which was discovered in 2006. We will speculate as to why
      vitamin D, cod liver oil, sunshine, and phototherapy are no longer being used to
      treat tuberculosis, in spite of their proven efficacy in safely treating this
      disease dating back to the early 1800's. In fact, in 1903 the Nobel Prize in
      Medicine or Physiology was awarded to a physician who was able to cure hundreds
      of cases of long-standing lupus vulgaris (cutaneous TB) with refracted light rays
      from an electric arc lamp. Vitamin D, cod liver oil, sunshine, and phototherapy
      have never been shown to lose their ability to safely eradicate tuberculosis
      infections, and deserve consideration to be re-examined as first-line treatments
      for tuberculosis. These treatments have the potential to help cost-effectively
      and safely end the global TB epidemic.

PMID- 28756295
TI  - Actin alpha cardiac muscle 1 gene expression is upregulated in the skeletal
      muscle of men undergoing androgen deprivation therapy for prostate cancer.
AB  - Androgen deprivation therapy (ADT) decreases muscle mass and function but no
      human studies have investigated the underlying genetic or cellular effects. We
      tested the hypothesis that ADT will lead to changes in skeletal muscle gene
      expression, which may explain the adverse muscle phenotype seen clinically. We
      conducted a prospective cohort study of 9 men with localised prostate cancer who
      underwent a vastus lateralis biopsy before and after 4 weeks of ADT. Next
      generation RNA sequencing was performed and genes differentially expressed
      following ADT underwent gene ontology mining using Ingenuity Pathway Analysis.
      Differential expression of genes of interest was confirmed by quantitative PCR (Q
      PCR) on gastrocnemius muscle of orchidectomised mice and sham controls
      (n=11/group). We found that in men, circulating total testosterone decreased from
      16.5+/-4.3nmol/L at baseline to 0.4+/-0.15nmol/L post-ADT (p<0.001). RNA
      sequencing identified 19 differentially expressed genes post-ADT (all p<0.05
      after adjusting for multiple testing). Gene ontology mining identified 8 genes to
      be of particular interest due to known roles in androgen-mediated signalling;
      ABCG1, ACTC1, ANKRD1, DMPK, THY1, DCLK1, CST3 were upregulated and SLC38A3 was
      downregulated post-ADT. Q-PCR in mouse gastrocnemius muscle confirmed that only
      one gene, Actc1 was concordantly upregulated (p<0.01) in orchidectomised mice
      compared with controls. In conclusion, given that ACTC1 upregulation is
      associated with improved muscle function in certain myopathies, we hypothesise
      that upregulation of ACTC1 may represent a compensatory response to ADT-induced
      muscle loss. Further studies will be required to evaluate the role and function
      of ACTC1.

PMID- 28756297
TI  - Liver disease predicts mortality in patients with X-linked immunodeficiency with
      hyper-IgM but can be prevented by early hematopoietic stem cell transplantation.

PMID- 28756298
TI  - Physical activity and body image among men and boys: A meta-analysis.
AB  - Three meta-analytic reviews have concluded that physical activity is positively
      related to body image. Historically, research regarding physical activity and
      body image has been disproportionately focused on female samples. For example,
      the most recent meta-analysis (2009) extracted 56 effect sizes for women and only
      12 for men. The current paper provides an update to the literature regarding the
      relationship between physical activity and body image among men and boys across
      84 individual effect sizes. The analysis also provides insight regarding
      moderator variables including participant age, and physical activity type and
      intensity. Overall, physical activity was positively related to body image among
      men and boys with various moderator variables warranting further investigation.
      Pragmatic implications are discussed as well as the limitations within existing
      research and need for additional research to further understand moderator and
      mediator variables.

PMID- 28756296
TI  - Pathway discovery using transcriptomic profiles in adult-onset severe asthma.
AB  - BACKGROUND: Adult-onset severe asthma is characterized by highly symptomatic
      disease despite high-intensity asthma treatments. Understanding of the underlying
      pathways of this heterogeneous disease is needed for the development of targeted
      treatments. Gene set variation analysis is a statistical technique used to
      identify gene profiles in heterogeneous samples. OBJECTIVE: We sought to identify
      gene profiles associated with adult-onset severe asthma. METHODS: This was a
      cross-sectional, observational study in which adult patients with adult-onset of
      asthma (defined as starting at age >=18 years) as compared with childhood-onset
      severe asthma (<18 years) were selected from the U-BIOPRED cohort. Gene
      expression was assessed on the total RNA of induced sputum (n = 83), nasal
      brushings (n = 41), and endobronchial brushings (n = 65) and biopsies (n = 47)
      (Affymetrix HT HG-U133+ PM). Gene set variation analysis was used to identify
      differentially enriched predefined gene signatures of leukocyte lineage,
      inflammatory and induced lung injury pathways. RESULTS: Significant
      differentially enriched gene signatures in patients with adult-onset as compared
      with childhood-onset severe asthma were identified in nasal brushings (5
      signatures), sputum (3 signatures), and endobronchial brushings (6 signatures).
      Signatures associated with eosinophilic airway inflammation, mast cells, and
      group 3 innate lymphoid cells were more enriched in adult-onset severe asthma,
      whereas signatures associated with induced lung injury were less enriched in
      adult-onset severe asthma. CONCLUSIONS: Adult-onset severe asthma is
      characterized by inflammatory pathways involving eosinophils, mast cells, and
      group 3 innate lymphoid cells. These pathways could represent useful targets for
      the treatment of adult-onset severe asthma.

PMID- 28756299
TI  - Are the size and composition of the paraspinal muscles associated with low back
      pain? A systematic review.
AB  - BACKGROUND CONTEXT: Although previous studies have investigated the association
      between paraspinal muscle morphology and low back pain (LBP), the results are
      conflicting. PURPOSE: This systematic review examined the relationship between
      size and composition of the paraspinal muscles and LBP. STUDY DESIGN/SETTING: A
      systematic review was carried out. PATIENT SAMPLE: No patient sample was
      required. OUTCOME MEASURES: This review had no outcome measures. METHODS: A
      systematic search of electronic databases was conducted to identify studies
      investigating the association between the cross-sectional area or fatty
      infiltration of the paraspinal muscles (erector spinae, multifidus, psoas, and
      quadratus lumborum) and LBP. Descriptive data regarding study design and
      methodology were tabulated and a risk of bias assessment was performed. RESULTS:
      Of the 119 studies identified, 25 met the inclusion criteria. Eight studies were
      reported as having low to moderate risk of bias. There was evidence for a
      negative association between cross-sectional area (CSA) of multifidus and LBP,
      but conflicting evidence for a relationship between erector spinae, psoas, and
      quadratus lumborum CSA and LBP. Moreover, there was evidence to indicate
      multifidus CSA was predictive of LBP for up to 12 months in men, but insufficient
      evidence to indicate a relationship for longer time periods. Although there was
      conflicting evidence for a relationship between multifidus fat infiltration and
      LBP, there was no or limited evidence for an association for the other paraspinal
      musculature. CONCLUSIONS: This review found evidence that multifidus CSA was
      negatively associated with and predictive of LBP up to 12 months but conflicting
      evidence for an association between erector spinae, psoas, and quadratus lumborum
      CSA and LBP. To further understand the role of the paraspinal musculature in LBP,
      there is a need for high-quality cohort studies which extend over both the short
      and longer term.

PMID- 28756300
TI  - Obesity and spinal epidural lipomatosis in cauda equina syndrome.
AB  - BACKGROUND CONTEXT: Although lumbar disc herniations are common, only a small
      portion of these herniations lead to cauda equina syndrome (CES), which is an
      uncommon but debilitating disorder. Why some patients with herniation develop
      CES, when most do not, remains unknown. Preexisting subclinical epidural
      lipomatosis may limit canal space such that an otherwise benign herniation causes
      CES. PURPOSE: This study determines whether patients with an acute disc
      herniation and CES have a greater body mass index (BMI) and greater quantity of
      epidural fat compared with control subjects with non-CES symptomatic lumbar
      herniated discs. STUDY DESIGN/SETTING: A retrospective case-control series at a
      university-based level-1 trauma center was carried out. PATIENT SAMPLE: There
      were 33 CES and 66 control subjects identified from a prospectively maintained
      database of patients who underwent surgical management for a lumbar disc
      herniation between 2007 and 2012. Each CES case had two non-CES control patients
      matched by gender and age within 5 years except 5 CES cases that matched only one
      non-CES control. OUTCOME MEASURES: The outcome measures included weight, height,
      age, gender, and BMI. Radiographic outcome measures included the proportion of
      lumbar spinal canal occupied by fat and herniated disc on preoperative magnetic
      resonance imaging. METHODS: Patient charts and preoperative radiographs were
      retrospectively reviewed. For each patient, a blinded reviewer determined the
      proportion of lumbar spinal canal occupied by fat, and the maximal proportion of
      the canal occupied by herniated material at the involved level. Patient
      demographics and radiographic measures were compared between CES and control
      groups using chi-square or Student t tests. A second blinded reviewer re-assessed
      a series of radiographs, and the intraobserver variability was determined by
      Spearman correlation. Logistic regression was used to model the preoperative
      factors associated with having an acute disc herniation and CES. RESULTS: The CES
      cases had higher BMI (31.8 kg/m2, 95% confidence interval [CI] 29.5-34.0 vs. 28.1
      kg/m2, 95% CI 26.7-29.5 in controls; p=.007), focally narrower canals (14.6 mm,
      95% CI 13.8-15.3 mm vs. 16.4 mm, 95% CI 15.4-17.3 mm in controls; p=.003), and a
      greater percentage of spinal canal occupied by epidural fat (31.3%, 95% CI 26.1%
      36.6% vs. 21.9%, 95% CI 18.7%-25.1% in controls; p=.003) and herniated disc
      material (54.5%, 95% CI 46.9%-62.0% vs. 34.4%, 95% CI 30.3%-38.5% in controls;
      p<.0001). Logistic regression confirmed canal width at the involved level, BMI,
      amount of canal occupied disc, and proportion of canal occupied by fat as
      independent predictors of having an acute disc herniation and CES. CONCLUSIONS:
      Obesity is a risk factor for CES from disc herniation. The CES cases also had a
      greater amount of herniated material, focally narrower canal, and larger epidural
      fat deposits. The latter may be the mechanism linking obesity with CES.

PMID- 28756301
TI  - Effectiveness of psychological interventions delivered by non-psychologists on
      low back pain and disability: a qualitative systematic review.
AB  - BACKGROUND CONTEXT: Psychological treatments delivered by non-psychologists have
      been proposed as a way to increase access to care to address important
      psychological barriers to recovery in people with low back pain (LBP). PURPOSE:
      This review aimed to synthesize randomized controlled trials (RCTs) that assess
      the effectiveness of psychological interventions delivered by non-psychologists
      in reducing pain intensity and disability in adults with LBP, compared with usual
      care. STUDY DESIGN: A systematic review without meta-analysis was carried out.
      METHODS: Randomized controlled trials including adult patients with all types of
      musculoskeletal LBP were eligible. Interventions included those based on
      psychological principles and delivered by non-psychologists. The primary outcomes
      of interest were self-reported pain intensity and disability. Information sources
      included Medline, EMBASE, and the Cochrane Central Registrar for Controlled
      Trials. The Cochrane Collaboration's tool for assessing risk of bias was used for
      the evaluation of internal validity. RESULTS: There were 1,101 records
      identified, 159 were assessed for eligibility, 16 were critically appraised, and
      11 studies were included. Mild to moderate risk of bias was present in the
      included studies, with personnel and patient blinding, treatment fidelity, and
      attrition being the most common sources of bias. Considerable heterogeneity
      existed for patient population, intervention components, and comparison groups.
      Although most studies demonstrated statistical and clinical improvements in pain
      and disability, few were statistically superior to the comparison group.
      CONCLUSIONS: Consistent with the broader psychological literature, psychological
      interventions delivered by non-psychologists have modest effects on low back pain
      and disability. Additional high quality research is needed to understand what
      patients are likely to respond to psychological interventions, the appropriate
      dose to achieve the desired outcome, the amount of training required to implement
      psychological interventions, and the optimal procedures to ensure treatment
      fidelity.

PMID- 28756302
TI  - Both positive and negative beliefs are important in patients with spine pain:
      findings from the Occupational and Industrial Orthopaedic Center registry.
AB  - BACKGROUND CONTEXT: Negative beliefs are known to influence treatment outcome in
      patients with spine pain (SP). The impact of positive beliefs is less clear.
      PURPOSE: We aimed to assess the influence of positive and negative beliefs on
      baseline and treatment responses in patients with SP. STUDY DESIGN/SETTING: A
      retrospective cross-sectional and longitudinal analysis of prospectively
      collected data of outpatient physical therapy patients with SP was carried out.
      Questionnaires administered before and during treatment included the STarT Back
      distress scale (negative beliefs), and expectation and self-efficacy questions
      (positive beliefs). PATIENT SAMPLE: Patients with SP with a baseline assessment
      and follow-up assessment comprised the study sample. OUTCOME MEASURE: Perceived
      disability was measured using the Oswestry Disability Index (ODI) or the Neck
      Disability Index (NDI). A clinical meaningful change (minimum clinically
      important difference [MCID]) was defined as decrease in ODI or NDI of >=30%.
      METHODS: We used the Akaike Information Criterion from the first imputed dataset
      of the prediction model to select predictor variables. Prediction models were
      fitted to the outcome variables. RESULTS: In the cross-sectional analysis, 1,695
      low back pain (LBP) episodes and 487 neck pain (NP) episodes were analyzed. STarT
      Back Screening Tool (SBST)-distress was positively associated with perceived
      disability in both LBP (beta 2.31, 95% confidence interval [CI] 1.75-2.88) and NP
      (beta 2.57, 95% CI 1.47-3.67). Lower self-efficacy was negatively associated with
      more perceived disability for LBP (beta 0.50, 95% CI 0.29-0.72) but not for NP,
      whereas less positive expectations was associated with more perceived disability
      in NP (beta 0.57, 95% CI 0.02-1.12) but not in LBP. In the longitudinal analysis,
      607 LBP episodes (36%) and 176 (36%) NP episodes were included. SBST-distress did
      not predict treatment outcome in spine patients. In LBP, patients with a lower
      positive expectation were less likely to experience an MCID in perceived
      disability (odds ratio [OR] per point increase 0.89, 95% CI 0.83-0.96), and there
      was a similar trend in NP (OR per point increase 0.90, 95% CI 0.79-1.03). In
      patients with LBP, lower self-efficacy at baseline was associated with a higher
      likelihood that an MCID was achieved (OR per point increase 1.09, 95% CI 1.01
      1.19). In NP, self-efficacy was not included in the final model. CONCLUSIONS: Our
      study demonstrates that both negative and positive beliefs are associated with
      perceptions of disability. However, in this study, only positive beliefs were
      associated with treatment outcome.

PMID- 28756304
TI  - Chemomechanically engineered 3D organotypic platforms of bladder cancer dormancy
      and reactivation.
AB  - Tumors undergo periods of dormancy followed by reactivation leading to metastatic
      disease. Arrest in the G0/G1 phase of the cell cycle and resistance to
      chemotherapeutic drugs are key hallmarks of dormant tumor cells. Here, we
      describe a 3D platform of bladder cancer cell dormancy and reactivation
      facilitated by a novel aminoglycoside-derived hydrogel, Amikagel. These 3D
      dormant tumor microenvironments (3D-DTMs) were arrested in the G0/G1 phase and
      were highly resistant to anti-proliferative drugs. Inhibition of targets in the
      cellular protein production machinery led to induction of endoplasmic reticulum
      (ER) stress and complete ablation of 3D-DTMs. Nanoparticle-mediated calcium
      delivery significantly accelerated ER stress-mediated 3D-DTM death. Transfer of
      3D-DTMs onto weaker and adhesive Amikagels resulted in selective reactivation of
      a sub-population of N-cadherin deficient cells from dormancy. Whole-transcriptome
      analyses further indicated key biochemical differences between dormant and
      proliferative cancer cells. Taken together, our results indicate that 3D bladder
      cancer microenvironments of dormancy and reactivation can facilitate fundamental
      advances and novel drug discovery in cancer.

PMID- 28756305
TI  - Age assessment in canine and premolar by cervical axial sections of cone-beam
      computed tomography.
AB  - Age estimation in adults is a challenge in both anthropological and forensic
      situations compared to sub-adults age estimation. The present study explored, for
      the first time, the cervical zone of single rooted teeth. The deposition of
      secondary dentin is responsible for a decrease in the volume of the dental pulp
      cavity with aging, and therefore is often used as an age indicator. The current
      study aimed at estimating the chronological age among adults by measuring the
      pulp/dentin area ratio (physiological ratio) by axial sections at cervical region
      of maxillary canine and mandibular second premolar. The sample consisted of 120
      cone beam CT images of 120 Tunisians whose age ranged from 22 to 67, from the
      database of a private clinic of radiology. The first axial section of chosen
      teeth without enamel was selected. Linear regression models were derived for
      canine, premolar and for all variables to predict the age. They indicated that
      dentin deposition on canine and premolar have almost the same correlation with
      age (r=-0.838 and -0.837 respectively). The residual standard errors (RSE), when
      these regression equations applied for the entire sample, were ranged between
      8.27, 8.29 and 7.06 for canine, premolar and for all variables respectively.
      Tested for younger ages (from 22 to 44years) the RSE decreased considerably and
      thus ranged between 4.32, 4.72 and 4.05. The outcomes of this study show that the
      physiological ratio is a useful variable for assessing age with a satisfying
      accuracy.

PMID- 28756306
TI  - Atypical responses in patients with advanced melanoma, lung cancer, renal-cell
      carcinoma and other solid tumors treated with anti-PD-1 drugs: A systematic
      review.
AB  - Anti-programmed death receptor 1 (PD-1) drugs nivolumab and pembrolizumab were
      recently approved for the treatment of advanced melanoma and other solid tumors.
      Atypical patterns of response (i.e. tumor shrinkage or stabilization after
      initial progression) were observed in about 10% of metastatic melanoma patients
      treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) drug
      ipilimumab and were associated with improved survival; however, the rate of
      atypical response patterns to anti-PD-1 therapy is not clear. An electronic
      search was performed to identify clinical trials evaluating response to anti-PD-1
      therapy with nivolumab and pembrolizumab in patients with advanced solid tumors.
      Thirty-eight studies were included in our analysis for a total of 7069 patients
      with advanced cancer treated with anti-PD-1 therapy. Responses were evaluated by
      unconventional response criteria in 19 trials and were observed for all cancer
      types but tumors with mismatch-repair deficiency and head and neck squamous cell
      carcinoma. Overall, 151 atypical responses were observed in 2400 patients (6%)
      evaluated by unconventional response criteria. The results of our systematic
      review highlight the clinical relevance of unconventional responses to anti-PD-1
      therapy and support further investigation into the development of tools that may
      assist evaluation of the antitumor activity of immunotherapy.

PMID- 28756307
TI  - Identification and comparison of candidate odorant receptor genes in the
      olfactory and non-olfactory organs of Holotrichia oblita Faldermann by
      transcriptome analysis.
AB  - A sophisticated olfactory system is part of the explanation for the prominence of
      insects among animals because of the essential roles of the olfactory system in
      foraging, host seeking, mating, ovipositing and avoiding toxic substances. In
      this study, we sequenced and analysed the transcriptomes of olfactory tissue
      (antennae) and non-olfactory tissue (legs) of the scarab beetle, Holotrichia
      oblita Faldermann, which is a serious underground pest in China. We obtained
      approximately 80.2 million 150bp reads that were assembled into 61,038 unigenes
      with an average length of 890bp. Among the transcripts, 70% of the unigenes were
      annotated. A total of 44 odorant receptors (ORs) and 9 ionotropic receptors (IRs)
      were identified based on homology searches. Then, quantitative real-time PCR
      experiments were performed to investigate the expression patterns of 32 putative
      chemosensory genes. The results showed that these genes were highly expressed in
      olfactory organs (antennae) and might play a key role in the olfaction-related
      behaviours in H. oblita. Based on the results of our phylogenetic analysis and
      the detailed tissue and sex-biased expression characteristics, the different
      roles of the receptor proteins in the olfactory system were also indicated. The
      results of this study will provide the foundation for further understanding of
      the olfactory odorant receptors of H. oblita at the molecular level and
      ultimately help to develop novel targets for manipulating this pest.

PMID- 28756303
TI  - Four pathways of CD1 antigen presentation to T cells.
AB  - CD1a, CD1b, CD1c and CD1d proteins migrate through distinct subcellular
      compartments of antigen presenting cells and so can be considered to take four
      separate pathways leading to display of lipid antigens to T cell receptors. This
      review discusses the intersection of CD1 trafficking and lipid antigen loading
      mechanisms in cells, highlighting key controversies relating to CD1 gene
      expression, size mismatches between antigens and CD1 binding clefts and
      unexpected mechanisms of T cell receptor-based recognition.

PMID- 28756308
TI  - Self-reported shift work, recall bias, and belief about disease causation in a
      case-control study of breast cancer.
AB  - BACKGROUND: Recall bias is a potential source of misclassification in case
      control studies. Studies have shown that the association between exposure and
      disease can differ according to participants' beliefs or knowledge about the
      effect of that exposure on disease. We investigated the association between
      belief about breast cancer causation and self-reported shift work exposure in a
      case-control study. METHODS: Women completed a questionnaire asking whether they
      believed that shift work caused cancer either before or after reporting their
      history of shift work. We measured: whether belief modified the association
      between reported shift work and disease; whether belief was associated with
      reported shift work exposure; and whether being prompted to recall shift work
      exposure was associated with an increased likelihood of believing that shift work
      increased breast cancer risk. RESULTS: There was a significant association
      between believing shift work increased breast cancer risk and reporting exposure
      to shift work. Being prompted to recall shift work was not associated with a
      belief that shift work increased risk. CONCLUSION: The association between pre
      existing belief about breast cancer risk and reported shift work is likely to be
      due to exposed individuals believing that exposure increases risk, rather than
      resulting from recall bias.

PMID- 28756309
TI  - Activation of brain glucose metabolism ameliorating cognitive impairment in
      APP/PS1 transgenic mice by electroacupuncture.
AB  - An essential feature of Alzheimer's disease (AD) is implicated in brain energy
      metabolic impairment that is considered underlying pathogenesis of cognitive
      impairment. Therefore, therapeutic interventions to allay cognitive deficits that
      target energy metabolism may be an efficacy strategy in AD. In this study, we
      found that electroacupuncture (EA) at the DU20 acupoint obviously increased
      glucose metabolism in specific brain regions such as cortex, hippocampus,
      cingulate gyrus, basal forebrain septum, brain stem, and cerebellum in APP/PS1
      transgenic mice by animal 18F-Fluoro-2-deoxy-D-Glucose (18F-FDG)/positron
      emission tomography (PET) imaging, accompanied by cognitive improvements in the
      spatial reference learning and memory and memory flexibility and novel object
      recognition performances. Further evidence shown energy metabolism occurred in
      neurons or non-neuronal cells of the cortex and hippocampus in terms of the co
      location of GLUT3/NeuN and GLUT1/GFAP. Simultaneously, metabolic homeostatic
      factors were critical for glucose metabolism, including phosphorylated adenosine
      monophosphate-activated protein kinase (AMPK) and AKT serine/threonine kinase.
      Furthermore, EA-induced phosphorylated AMPK and AKT inhibited the phosphorylation
      level of the mammalian target of rapamycin (mTOR) to decrease the accumulation of
      amyloid-beta (Abeta) in the cortex and hippocampus. These findings are concluded
      that EA is a potential therapeutic target for delaying memory decline and Abeta
      deposition of AD. The AMPK and AKT are implicated in the EA-induced cortical and
      hippocampal energy metabolism, which served as a contributor to improving
      cognitive function and Abeta deposition in a transgenic mouse model of AD.

PMID- 28756311
TI  - Neurogenesis impairment: An early developmental defect in Down syndrome.
AB  - Down syndrome (DS) is characterized by brain hypotrophy and intellectual
      disability starting from early life stages. Accumulating evidence shows that the
      phenotypic features of the DS brain can be traced back to the fetal period since
      the DS brain exhibits proliferation potency reduction starting from the critical
      time window of fetal neurogenesis. This defect is worsened by the fact that
      neural progenitor cells exhibit reduced acquisition of a neuronal phenotype and
      an increase in the acquisition of an astrocytic phenotype. Consequently, the DS
      brain has fewer neurons in comparison with the typical brain. Although apoptotic
      cell death may be increased in DS, this does not seem to be the major cause of
      brain hypocellularity. Evidence obtained in brains of individuals with DS, DS
      derived induced pluripotent stem cells (iPSCs), and DS mouse models has provided
      some insight into the mechanisms underlying the developmental defects due to the
      trisomic condition. Although many triplicated genes may be involved, in the light
      of the studies reviewed here, DYRK1A, APP, RCAN1 and OLIG1/2 appear to be
      particularly important determinants of many neurodevelopmental alterations that
      characterize DS because their triplication affects both the proliferation and
      fate of neural precursor cells as well as apoptotic cell death. Based on the
      evidence reviewed here, pathways downstream to these genes may represent
      strategic targets, for the design of possible interventions.

PMID- 28756310
TI  - Peroxyl radical- and photo-oxidation of glucose 6-phosphate dehydrogenase
      generates cross-links and functional changes via oxidation of tyrosine and
      tryptophan residues.
AB  - Protein oxidation is a frequent event as a result of the high abundance of
      proteins in biological samples and the multiple processes that generate oxidants.
      The reactions that occur are complex and poorly understood, but can generate
      major structural and functional changes on proteins. Current data indicate that
      pathophysiological processes and multiple human diseases are associated with the
      accumulation of damaged proteins. In this study we investigated the mechanisms
      and consequences of exposure of the key metabolic enzyme glucose-6-phosphate
      dehydrogenase (G6PDH) to peroxyl radicals (ROO*) and singlet oxygen (1O2), with
      particular emphasis on the role of Trp and Tyr residues in protein cross-linking
      and fragmentation. Cross-links and high molecular mass aggregates were detected
      by SDS-PAGE and Western blotting using specific antibodies. Amino acid analysis
      has provided evidence for Trp and Tyr consumption and formation of oxygenated
      products (diols, peroxides, N-formylkynurenine, kynurenine) from Trp, and di
      tyrosine (from Tyr). Mass spectrometric data obtained after trypsin-digestion in
      the presence of H216O and H218O, has allowed the mapping of specific cross-linked
      residues and their locations. These data indicate that specific Tyr-Trp and di
      Tyr cross-links are formed from residues that are proximal and surface
      accessible, and that the extent of Trp oxidation varies markedly between sites.
      Limited modification at other residues is also detected. These data indicate that
      Trp and Tyr residues are readily modified by ROO* and 1O2 with this giving
      products that impact significantly on protein structure and function. The
      formation of such cross-links may help rationalize the accumulation of damaged
      proteins in vivo.

PMID- 28756312
TI  - Hydrogen peroxide, nitric oxide and ATP are molecules involved in cardiac
      mitochondrial biogenesis in Diabetes.
AB  - This study, in an experimental model of type I Diabetes Mellitus in rats, deals
      with the mitochondrial production rates and steady-state concentrations of H2O2
      and NO, and ATP levels as part of a network of signaling molecules involved in
      heart mitochondrial biogenesis. Sustained hyperglycemia leads to a cardiac
      compromise against a work overload, in the absence of changes in resting cardiac
      performance and of heart hypertrophy. Diabetes was induced in male Wistar rats by
      a single dose of Streptozotocin (STZ, 60mg * kg-1, ip.). After 28 days of STZ
      injection, rats were sacrificed and hearts were isolated. The mitochondrial mass
      (mg mitochondrial protein * g heart-1), determined through cytochrome oxidase
      activity ratio, was 47% higher in heart from diabetic than from control animals.
      Stereological analysis of cardiac tissue microphotographs showed an increase in
      the cytosolic volume occupied by mitochondria (30%) and in the number of
      mitochondria per unit area (52%), and a decrease in the mean area of each
      mitochondrion (23%) in diabetic respect to control rats. Additionally, an
      enhancement (76%) in PGC-1alpha expression was observed in cardiac tissue of
      diabetic animals. Moreover, heart mitochondrial H2O2 (127%) and NO (23%)
      productions and mtNOS expression (132%) were higher, while mitochondrial ATP
      production rate was lower (~ 40%), concomitantly with a partial-mitochondrial
      depolarization, in diabetic than in control rats. Changes in mitochondrial H2O2
      and NO steady-state concentrations and an imbalance between cellular energy
      demand and mitochondrial energy transduction could be involved in the signaling
      pathways that lead to the novo synthesis of mitochondria. However, this
      compensatory mechanism triggered to restore the mitochondrial and tissue normal
      activities, did not lead to competent mitochondria capable of supplying the
      energetic demands in diabetic pathological conditions.

PMID- 28756313
TI  - Differences in cardio-ankle vascular index in a general Mediterranean population
      depending on the presence or absence of metabolic cardiovascular risk factors.
AB  - BACKGROUND AND AIMS: The main aim of this study is to describe the differences in
      the cardio-ankle vascular index (CAVI) in individuals with metabolic
      cardiovascular risk factors or a previous history of vascular diseases (WCVRF)
      compared to healthy individuals (free of risk factors and previous history of
      vascular diseases; FCVRF) in a general Mediterranean population. The secondary
      aim is to describe the proportion of CAVI>=9 depending on the cardiovascular risk
      category in both CVRF groups by sex. METHODS: The study is a descriptive analysis
      of 2613 participants randomly selected in the Girona province (Catalonia, Spain).
      RESULTS: CAVI mean differences between sexes and age categories in both CVRF
      groups followed the same pattern, the FCVRF group (men 25.2%; women 14.4%) in
      turn had a lower prevalence of CAVI>=9 than the WCVRF group (men 57.9%; women
      51.8%). The percentage of men and women with CAVI>=9 with low risk was 13.9% and
      11.3% in the FCVRF group, and 31.8% and 42.0% in the WCVRF group; with moderate
      risk, it was 55.8% and 10.0% in the FCVRF group and 60.3% and 49.0% in the WCVRF
      group. CONCLUSIONS: In both sexes, FCVRF groups had a lower prevalence of CAVI>=9
      as well as lower mean CAVI scores, across all 10 year-age categories from 40 to
      69 years, than WCVRF groups. Moreover, CAVI>=9 was frequent in individuals with
      low and moderate coronary risk in the WCVRF group but also in the FCVRF group.
      These results suggest that CAVI assessment to detect asymptomatic
      arteriosclerosis could be a useful tool to improve cardiovascular risk
      stratification.

PMID- 28756314
TI  - Incorporating twitter-based human activity information in spatial analysis of
      crashes in urban areas.
AB  - The primary objective of this study was to investigate how to incorporate human
      activity information in spatial analysis of crashes in urban areas using Twitter
      check-in data. This study used the data collected from the City of Los Angeles in
      the United States to illustrate the procedure. The following five types of data
      were collected: crash data, human activity data, traditional traffic exposure
      variables, road network attributes and social-demographic data. A web crawler by
      Python was developed to collect the venue type information from the Twitter check
      in data automatically. The human activities were classified into seven categories
      by the obtained venue types. The collected data were aggregated into 896 Traffic
      Analysis Zones (TAZ). Geographically weighted regression (GWR) models were
      developed to establish a relationship between the crash counts reported in a TAZ
      and various contributing factors. Comparative analyses were conducted to compare
      the performance of GWR models which considered traditional traffic exposure
      variables only, Twitter-based human activity variables only, and both traditional
      traffic exposure and Twitter-based human activity variables. The model
      specification results suggested that human activity variables significantly
      affected the crash counts in a TAZ. The results of comparative analyses suggested
      that the models which considered both traditional traffic exposure and human
      activity variables had the best goodness-of-fit in terms of the highest R2 and
      lowest AICc values. The finding seems to confirm the benefits of incorporating
      human activity information in spatial analysis of crashes using Twitter check-in
      data.

PMID- 28756315
TI  - Small angle neutron scattering study of the conformation of poly(ethylene oxide)
      dissolved in deep eutectic solvents.
AB  - HYPOTHESIS: The conformation of poly(ethylene oxide) (PEO) in deep eutectic
      solvents (DESs) is determined by the polymer-solvent interactions, especially
      hydrogen bonding interactions. The hypothesis for this work is that the hydrogen
      bonding environment of a DES can be varied via changing the cation or hydrogen
      bond donor (HBD), and therefore the solvent quality for PEO; the anion species
      will also effect hydrogen bonding, but this is not examined here. EXPERIMENTS:
      Small angle neutron scattering (SANS) is used to probe the concentration
      dependent conformation of 36kDa PEO dissolved in DESs formed by mixing ethyl or
      butyl ammonium bromide with a molecular HBD (glycerol or ethylene glycol) in a
      1:2 molar ratio. FINDINGS: The radius of gyration (Rg), Flory exponent and
      crossover concentration (c*) from the dilute to the semi-dilute regime of PEO in
      the DESs revealed by SANS and Zimm plot analysis show that these DESs are
      moderately good solvents for PEO. When the ammonium alkyl chain length is
      increased, the hydrogen bond density per unit volume decreases, and with it the
      solvent quality for PEO. The solvent quality is improved when the HBD is changed
      from glycerol to ethylene glycol due to differences in the hydrogen bonding
      environment for PEO.

PMID- 28756316
TI  - Dissipative particle dynamics simulations reveal the pH-driven micellar
      transition pathway of monorhamnolipids.
AB  - Dissipative particle dynamics (DPD) simulation has been used to study the effect
      of pH on the morphology transition of micelles assembled by monorhamnolipids
      (monoRLs). Results show that micellar structures and transition modes with
      increasing mass concentrations are multiform due to the changeable hydrophilicity
      of pH-responsive beads at different pH levels. Various chaotic multilayer
      aggregations of monoRLs are observed at low pH (pH<4.0) whereas well-ordered
      single-layer structures are obtained at high pH (pH>7.4). At medium pH region
      (4.0<pH<7.4), morphologies with semi-chaotic structures will transform from
      multilayer to single layer with increasing pH due to the hydrophilicity increase
      of micelles. In addition, three micellar transition modes are built by varying
      the hydrophilicity of pH-responsive beads and validated by solvent accessible
      surface areas (SASAs) as a function of mass concentrations. This work is expected
      to trigger further studies on the stimuli-driven phenomena of glycolipids.

PMID- 28756317
TI  - Sol-gel 3-glycidoxypropyltriethoxysilane finishing on different fabrics: The role
      of precursor concentration and catalyst on the textile performances and cytotoxic
      activity.
AB  - In this paper, the influence of 3-glycidoxypropyltriethoxysilane (GPTES) based
      organic-inorganic coatings on the properties of treated textile fabrics was
      studied. All experimental results were deeply analyzed and thereafter correlated
      with the employed silica precursor concentration and with the presence of the
      BF3OEt2 (Boron trifluoride diethyl etherate), used as epoxy ring opening
      catalyst. SEM analysis, FT-IR spectroscopy, X-ray Photoelectron Spectroscopy
      (XPS), thermogravimetric analysis (TGA) and washing fastness tests of the sol-gel
      treated cotton fabric samples were firstly exploited in order to characterize the
      morphological and structural features of the achieved coatings. Finally, the
      influence of the resulting nanohybrid coatings was explored in terms of abrasion
      resistance, tensile strength and elongation properties of treated cotton,
      polyester and silk fabrics. The catalyst amounts seem to strongly improve the
      formation of coatings, but still they do not influence the wear resistance of
      treated textile fabrics to the same extent. Indeed, it was found that increasing
      catalyst/GPTES ratio leads to a more cross linked inorganic 3D-network. GPTES
      itself was not found to affect the bulk properties of the selected textile and
      the resulting coatings were not so rigid to hardly modify the mechanical
      properties of the treated samples. Finally, it is worth mentioning that in all
      case the obtained 3-glycidoxypropyltriethoxysilane-based chemical finishing have
      shown no cytotoxic effects on human skin cells.

PMID- 28756318
TI  - Highly effective carbon sphere counter electrodes based on different substrates
      for dye-sensitized solar cell.
AB  - A monodisperse carbon sphere with high uniformity, high catalytic activity and
      conductivity are successfully synthesized. Versatile counter electrodes using
      this carbon sphere catalyst on different substrates of fluorine-doped tin oxide
      (FTO) glass, indium-doped tin oxide polyethylenena phthalate (ITO-PEN), and Ti
      foil are fabricated for dye-sensitized solar cell (DSC). The impacts of
      substrates on the catalytic activities of the carbon sphere counter electrodes
      have been also evaluated by electrochemical analysis technologies, such as cyclic
      voltammetry, electrochemical impedance spectroscopy and Tafel polarization
      curves. With cobalt electrolyte, the DSC using carbon sphere counter electrodes
      based on FTO glass, ITO-PEN, and Ti substrates yield high power conversion
      efficiency values of 8.57%, 6.66%, and 9.10%, respectively. The catalytic
      activities of the prepared carbon sphere counter electrodes on different
      substrates are determined by the apparent activation energy for the cobalt redox
      couple regeneration on these electrodes.

PMID- 28756319
TI  - Facile preparation of fluffy N-doped carbon modified with Ag nanoparticles as a
      highly active and reusable catalyst for catalytic reduction of nitroarenes.
AB  - Novel fluffy smoke like mesoporous N-doped carbon (mNC) was prepared through a
      facile one-pot carbonization method using the low-cost melamine and
      polyacrylonitrile as the precursor materials. The obtained mNC material exhibits
      a high surface area, rich nitrogen content and can be used as an ideal catalyst
      support to fabricate noble metal modified nanocatalysts. Here, small Ag
      nanoparticles were supported on the mNC material with high dispersion to give the
      Ag/mNC nanocatalyst. The obtained Ag/mNC nanocatalyst was used in the catalytic
      reduction of nitroarenes and showed excellent catalytic activity, probably due to
      the small Ag NPs which highly dispersed on the fluffy mNC material that can
      enhance the accessibility and mass transfer, and subsequently enhance the
      catalytic activity. It is worth mentioning that, in the catalytic reduction of
      nitroarenes with halogenated groups, almost no dehalogenation phenomenon can be
      observed, which implies the superior catalytic chemoselectivity of the Ag/mNC
      nanocatalyst.

PMID- 28756321
TI  - Enhanced nucleation of diamond on three dimensional tools via stabilized
      colloidal nanodiamond in electrostatic self-assembly seeding process.
AB  - Nanocrystalline diamond particles are promising candidates for copious
      applications in materials science, biology and electronics. In this work, diamond
      nucleation density was unprecedentedly enhanced via a non-invasive electrostatic
      self-assembly seeding approach. By addition of glutamic acid to the nanodiamond
      seeding solution, the positively charged amino-group of glutamic acid, which is
      adsorbed on nanodiamond particles, enhances the adsorption on negative charged
      cemented carbide substrate. The highest nucleation density (1.0*1010cm-2) was
      achieved by utilizing glutamic acid at pH 4 as well as DI water at pH 2.2. This
      density was 20-1000 times higher than most earlier published results on WC-Co
      substrate. The concentration of the organic molecule, pH, concentration of ND
      particles and ultrasonication seeding time were found to be important for the
      seeding process. The colloidal stability was tweaked by pH of the dispersion and
      concentration of glutamic acid. The optimized parameters for nanodiamond
      adsorption on WC-Co substrate were found to be pH 4 at a concentration of 7*10-5M
      of glutamic acid at a nanodiamond concentration of 0.005wt%, while the seeding
      was conducted for 30min. The short ultrasonication time inhibits aggregation and
      void formation due to peeling off of nanodiamond patches at prolonged seeding
      times. Moreover, diamond thin films were deposited uniformly and densely on end
      mills made of cemented carbide. This work indicates that electrostatic induced
      adsorption of diamond nanoparticles is crucial for the development of ultra-high
      nucleation densities for the growth of high performance nanocrystalline diamond
      films, especially for micro sized tools with sharp cutting edges. It may serve as
      an approach for pinhole-free ultra-thin films deposition on micro
      electromechanical system, and encapsulation coating in harsh environment.

PMID- 28756320
TI  - Surface tailoring of polyacrylate-grafted graphene oxide for controlled
      interactions at the biointerface.
AB  - The actual surface termination and lateral size of a nanomaterial is crucial in
      its interaction with biomolecules at the aqueous interface. Graphene oxide (GO)
      nanosheets have been demonstrated as promising nanoplatform for both diagnostic
      and therapeutic applications. To this respect, 'smart' GO nanocarriers have been
      obtained by the surface functionalisation with polymers sensitive, e.g., to pH,
      as the polyacrylate (PAA) case. In this work, hybrid GO/PAA samples prepared
      respectively at low (GOPAAthin) or high (GOPAAthick) monomer grafting ratio, were
      scrutinised both theoretically, by molecular dynamic calculations, and
      experimentally by a multitechnique approach, including spectroscopic (UV-visible,
      fluorescence, Raman, Attenuated-total reflectance-Fourier transformed infrared
      and X-ray photoelectron spectroscopies), spectrometric (time-of-flight secondary
      ion and electrospray ionisation mass spectrometries) and microscopic (atomic
      force and confocal microscopies) methods. The actual surface termination,
      evaluated in terms of the relative ratio between polar and dispersive groups at
      the surface of the GO/polymer systems, was found to correlate with the average
      orientation of hydrophilic/hydrophobic domains of albumin, used as model protein.
      Moreover, the comparison among GO, GO-PAAthin and GO-PAAthick in the optical
      response at the interface with aqueous solutions, both at acid and at
      physiological pH, showed that the hybrid GO-polymer platform could be suitable
      not only to exploit a pH-triggered drug release but also for a modulation of the
      GO intrinsic emission properties. Energy transfer experiments on the GO/polymer
      oxide/fluorescein-labelled albumin/doxorubicin assembly showed significant
      differences for GO and GO-PAA samples, thus demonstrating the occurrence of
      different electronic processes at the hybrid nano-bio-interfaces. Confocal
      microscopy studies of cellular uptake in neuroblastoma cells confirmed the
      promising potentialities of the developed nanoplatform for applications at the
      biointerface.

PMID- 28756322
TI  - A low cost additive-free facile synthesis of BiFeWO6/BiVO4 nanocomposite with
      enhanced visible-light induced photocatalytic activity.
AB  - In this study, visible light driven BiFeWO6/BiVO4 nanocomposite was synthesized
      via simple additive-free wet-chemical process. Various physicochemical
      characterization methods such as X-ray diffraction (XRD), fourier transform
      infrared (FT-IR), scanning electron microscopy (SEM), transmission electrons
      microscopy (TEM), energy dispersive spectroscopy (EDS) spectra, UV visible
      diffuse reflectance spectroscopy (DRS), photoluminescence (PL) and
      photoelectrochemical measurements were performed to examine the structure,
      surface morphology, electrochemical and optical behavior of the synthesized
      material. The photocatalytic performances of the as-synthesized materials were
      assessed by the photodegradation of methylene blue (MB) in visible-light
      illumination. The optimum BiFeWO6/BiVO4-2 nanocomposite has shown 95% degradation
      efficiency of (MB) after 90min. This is about 10-folds higher than that of
      pristine bismuth vanadate (BiVO4). This enhancement of photocatalytic
      performances is credited to the photogenerated electrons transfer from BiVO4 to
      BiFeWO6 catalyst surface and thereby reduced the recombination process. The
      higher photocatalytic activity, long-term stability and recyclability results
      have revealed that the BiFeWO6/BiVO4 nanocomposite could be an auspicious
      material for the elimination of organic contaminants present in the ecosystem.
      Moreover, a probable mechanism for the catalytic degradation of MB dye over
      BiFeWO6/BiVO4 system is also proposed based on experimental results.

PMID- 28756324
TI  - A colorimetric and electrochemical immunosensor for point-of-care detection of
      enterovirus 71.
AB  - Point-of-care detection of human enterovirus 71 (EV71), the major pathogen that
      causes hand, foot, and mouth disease (HFMD) among children, is urgently needed
      for early diagnosis and control of related epidemics. A colorimetric and
      electrochemical immunosensor for point-of-care detection of EV71 has been
      developed based on dual-labeled magnetic nanobeads amplification. The dual
      labeled magnetic nanobeads (DL-MBs) are fabricated by simultaneous immobilization
      of EV71 monoclonal antibody (mAb) and horseradish peroxidase (HRP) on magnetic
      nanobeads. By capturing EV71 virions in 20MUL sample on mAb modified AuNPs-coated
      ITO electrode and subsequently binding with DL-MBs, with the addition of TMB and
      H2O2, colorimetric signals corresponding to EV71 with a concentration of 1.0ngmL
      1 can be directly read out by naked eyes, making it possible towards point-of
      care detection of the virus. Furthermore, on the reduction of oxidized TMB on the
      electrode, electrochemical signal can be detected in the same detection cell
      without solution transfer, with a detection limit of 0.01ngmL-1. Validated with
      clinical samples, the colorimetric and electrochemical immunosensor shows a
      complete consistency with reverse transcription-polymerase chain reaction (RT
      PCR) results. So far as we know, this is the first report on EV71 detection using
      electrochemical method. The merits of this assay, including high sensitivity,
      ability for colorimetric detection and easy to operation, ensure a promising
      future in point-of-care diagnostics of virus related diseases.

PMID- 28756325
TI  - Estimated impact of multiple conceptuses per follicle on fecundity in the bitch.
AB  - Multiple conceptuses from one follicle due to multi-ovular follicles or
      monozygotic twins inflate the ratio between the numbers of conceptuses and
      corpora lutea and possibly the effect ascribed to experimental treatment. The aim
      of this study was to estimate the impact of multiple conceptuses per follicle on
      fecundity in the bitch. The numbers of conceptuses and corpora lutea of 105
      bitches originated from 7 published experimental studies and of 132 from
      ovariohysterectomies done in a private practice and a welfare organisation.
      Ninety five bitches, producing 597 conceptuses, had at least as many conceptuses
      as corpora lutea; 83 had as many, 10 had one more and 2 had 2 more. Bootstrap
      resampling on these 95 bitches let us to conclude that 12.6% of bitches are
      expected to produce more oocytes that are each capable of yielding a conceptus
      than the number of follicles that ovulate and that 2.35% of conceptuses are
      expected to be in excess of the number of follicles that ovulate. Applying the
      results of the current study to 2 earlier studies showed that multiple
      conceptuses from one follicle may, at maximum, have increased the effect ascribed
      to prostatic fluid by 0.022 and 0.024 conceptuses per corpus luteum, which is
      minor in relation to the magnitude of the ascribed effects of 0.34 and 0.22
      conceptuses per corpus luteum. The number of conceptuses relative to the number
      of corpora lutea provides a valid and precise measurement of fertility in the
      bitch.

PMID- 28756323
TI  - Electrochemical biosensing based on protein-directed carbon nanospheres embedded
      with SnOx and TiO2 nanocrystals for sensitive detection of tobramycin.
AB  - A series of nanocomposites comprised of homogeneous mesoporous carbon nanospheres
      embedded with SnOx (x = 0, 1, or 2) and TiO2 nanocrystals using bovine serum
      albumin (BSA) as template followed by calcinated at different temperatures (300,
      500, 700, and 900 degrees C) were prepared, and were denoted as SnOx@TiO2@mC.
      Then a novel electrochemical biosensing strategy for detecting tobramycin (TOB)
      based on the nanocomposites was constructed. The as-prepared SnOx@TiO2@mC
      nanocomposites not only possess high specific surface area and good
      electrochemical activity but also exhibit strong bioaffinity with the aptamer
      strands, therefore, they were applied as the scaffold for anchoring TOB-targeted
      aptamer and further used to sensitively detect trace TOB in aqueous solutions. By
      comparing the electrochemical biosensing responses toward TOB detection based on
      the four SnOx@TiO2@mC nanocomposites, the biosensing system constructed with
      SnOx@TiO2@mC900 (derived at 900 degrees C) demonstrated the highest determination
      efficiency, high selectivity, and good stability. In particular, the new proposed
      aptasensing method based on SnOx@TiO2@mC nanocomposite exhibits considerable
      potential for the quantitative detection of TOB in the biomedical field.

PMID- 28756326
TI  - Bovine serum albumin and skim-milk improve boar sperm motility by enhancing
      energy metabolism and protein modifications during liquid storage at 17  degrees
      C.
AB  - Both bovine serum albumin (BSA) and skim-milk have been reported to improve sperm
      quality, primarily by enhancing sperm motility, but the underlying molecular
      mechanism remains unknown. In this study, boar semen samples were collected and
      diluted with Androstar(r) Plus extender containing different concentrations (0,
      2, 4 g/l) of BSA and skim-milk. On days 0, 3, 5 and 7, the sperm motility
      parameters were determined using computer-assisted sperm analysis (CASA), and the
      ATP concentrations, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity and
      mitochondrial membrane potential were evaluated using commercial kits. The levels
      of protein phosphorylation, acylation and ubiquitination were analyzed by western
      blot. The results showed that supplementation with BSA and skim-milk provided
      higher sperm motility parameters, ATP levels, GAPDH activity and mitochondrial
      membrane potential than the control group (P < 0.05). Interestingly, we found
      that the levels of protein phosphorylation, acetylation and succinylation of the
      spermatozoa in the treated groups were dramatically higher than those in the
      control group (P < 0.05). Though the protein ubiquitination level had a
      decreasing trend, the change in ubiquitination modification was not significantly
      different between the control group and treated groups. Moreover, the changes in
      protein modifications between the BSA treated group and skim-milk treated group
      were not distinctly dissimilar. Taken together, these results suggest that BSA
      and skim-milk had a positive role in the regulation of boar sperm motility by
      influencing sperm protein modifications changes as well as increasing the GAPDH
      activity, mitochondrial membrane potential, and intracellular ATP content. This
      research provides novel insights into the molecular mechanisms underlying BSA and
      skim-milk protective effects on boar sperm in the male reproductive system and
      suggests the feasibility of using skim-milk instead of BSA as a boar semen
      extender supplement.

PMID- 28756329
TI  - Ventilation for thoracic surgery in the newborn: Don't forget high frequency
      oscillatory ventilation!

PMID- 28756328
TI  - Comparison of three stimulation sites on the pupillary dilation reflex amplitude
      evoked by a standardized noxious test.

PMID- 28756327
TI  - Axillary nerve block for a wrist fracture in a patient with facioscapulohumeral
      (Landouzy-Dejerine) disease.

PMID- 28756330
TI  - Does perfusion pressure offer more brain protection than haemoglobin level? A
      case of aortic injury during laparoscopic bariatric surgery.

PMID- 28756331
TI  - Association between augmented renal clearance and clinical failure of antibiotic
      treatment in brain-injured patients with ventilator-acquired pneumonia: A
      preliminary study.
AB  - OBJECTIVES: This preliminary study aimed to determine whether augmented renal
      clearance (ARC) impacts negatively on the clinical outcome in traumatic brain
      injured patients (TBI) treated for a first episode of ventilator-acquired
      pneumonia (VAP). METHODS: During a 5-year period, all TBI patients who had
      developed VAP were retrospectively reviewed to assess variables associated with
      clinical failure in multivariate analysis. Clinical failure was defined as an
      impaired clinical response with a need for escalating antibiotics during
      treatment and/or within 15 days after the end-of-treatment. Recurrence was
      considered if at least one of the initial causative bacterial strains was growing
      at a significant concentration from a second sample. Augmented renal clearance
      (ARC) was defined by an enhanced creatinine clearance exceeding 130mL/min/1.73m2
      calculated from a urinary sample during the first three days of antimicrobial
      therapy. MAIN RESULTS: During the study period, 223 TBI patients with VAP were
      included and 59 (26%) presented a clinical failure. Factors statistically
      associated with clinical failure were GSC<=7 (OR=2.2 [1.1-4.4], P=0.03), early
      VAP (OR=3.9 [1.9-7.8], P=0.0001), bacteraemia (OR=11 [2.2-54], P=0.003) and
      antimicrobial therapy<=7 days (OR=3.7 [1.8-7.4], P=0.0003). ARC was statistically
      associated with recurrent infections with an OR of 4.4 [1.2-16], P=0.03.
      CONCLUSION: ARC was associated with recurrent infection after a first episode of
      VAP in TBI patients. The optimal administration and dosing of the antimicrobial
      agents in this context remain to be determined.

PMID- 28756332
TI  - Central venous catheter placement during extracorporeal membrane oxygenation
      therapy.

PMID- 28756333
TI  - Zooming into plant ubiquitin-mediated endocytosis.
AB  - Endocytosis in plants plays an essential role, not only for basic cellular
      functions but also for growth, development, and environmental responses. Over the
      past few years, ubiquitin emerged as a major signal triggering the removal of
      plasma membrane proteins from the cell surface and promoting their vacuolar
      targeting. Detailed genetic, biochemical and imaging studies have provided
      initial insights into the precise mechanisms and roles of ubiquitin-mediated
      endocytosis in plants. Here, we summarize the present state of knowledge about
      the machinery involved in plant ubiquitin-mediated endocytosis and how this is
      coordinated in time and space to control the internalization and the endosomal
      sorting of endocytosed proteins.

PMID- 28756334
TI  - Error bounds for approximations with deep ReLU networks.
AB  - We study expressive power of shallow and deep neural networks with piece-wise
      linear activation functions. We establish new rigorous upper and lower bounds for
      the network complexity in the setting of approximations in Sobolev spaces. In
      particular, we prove that deep ReLU networks more efficiently approximate smooth
      functions than shallow networks. In the case of approximations of 1D Lipschitz
      functions we describe adaptive depth-6 network architectures more efficient than
      the standard shallow architecture.

PMID- 28756335
TI  - Computational approaches to understand the adverse drug effect on potassium,
      sodium and calcium channels for predicting TdP cardiac arrhythmias.
AB  - : Ion channels play a crucial role in the cardiovascular system. Our
      understanding of cardiac ion channel function has improved since their first
      discoveries. The flow of potassium, sodium and calcium ions across cardiomyocytes
      is vital for regular cardiac rhythm. Blockage of these channels, delays cardiac
      repolarization or tend to shorten repolarization and may induce arrhythmia.
      Detection of drug risk by channel blockade is considered essential for drug
      regulators. Advanced computational models can be used as an early screen for
      torsadogenic potential in drug candidates. New drug candidates that are
      determined to not cause blockage are more likely to pass successfully through
      preclinical trials and not be withdrawn later from the marketplace by
      manufacturer. Several different approved drugs, however, can cause a distinctive
      polymorphic ventricular arrhythmia known as torsade de pointes (TdP), which may
      lead to sudden death. The objective of the present study is to review the
      mechanisms and computational models used to assess the risk that a drug may TdP.
      KEY POINTS: There is strong evidence from multiple studies that blockage of the L
      type calcium current reduces risk of TdP. Blockage of sodium channels slows
      cardiac action potential conduction, however, not all sodium channel blocking
      antiarrhythmic drugs produce a significant effect, while late sodium channel
      block reduces TdP. Interestingly, there are some drugs that block the hERG
      potassium channel and therefore cause QT prolongation, but they are not
      associated with TdP. Recent studies confirmed the necessity of studying multiple
      distinctionic ion channels which are responsible for cardiac related diseases or
      TdP, to obtain an improved clinical TdP risk prediction of compound interactions
      and also for designing drugs.

PMID- 28756336
TI  - TNFalpha and IL-1beta in the synovial fluid facilitate mucosal-associated
      invariant T (MAIT) cell migration.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that
      primarily affect the joints and inflammatory cell migration into inflamed
      articular sites contribute to this disease. Among the inflammatory cells, human
      mucosal-associated invariant T (MAIT) cells were recently recognized as critical
      cellular component with a pathological role in RA. However, their migratory
      characteristics are poorly understood. The aim of this study was to determine
      whether human MAIT cells preferentially traffick to inflamed synovial sites in
      rheumatoid arthritis patients and to elucidate the underlying mechanism. First,
      we found that TNFalpha and IL-1beta were elevated in synovial fluid (SF) of RA
      patients, which resulted in increased expression of E-selectin, ICAM-1 and V-CAM
      1 on blood vessel endothelial cells. To understand whether TNFalpha and IL-1beta
      in the SF facilitated MAIT cell migration, we analyzed CD161+ TCRalpha7.2+ MAIT
      and other CD3+ T cells for differences in migratory capacity. Collectively, our
      results demonstrate that TNFalpha and IL-1beta in the SF facilitated MAIT cell
      migration dependent on expression of selectin ligand, sialyl LewisX (sLeX) and
      CCR6 on MAIT cells. We also showed that MAIT cells in the SF from RA patients
      equipped upregulated sLeX compared to the peripheral blood of RA patients and
      healthy persons, which suggest that TNFalpha and IL-1beta mediated expression of
      E-selectin preferentially attract sLeX mediated MAIT cell migration into the SF
      of RA patients.

PMID- 28756337
TI  - Epilepsy-related romantic and sexual relationship problems and concerns:
      Indications from Internet message boards.
AB  - The objective of this study was to, utilizing a Big Data set and innovative
      methods, explore romantic and sexual relationship-related concerns among people
      with epilepsy and their partners. We applied Word Adjacency Graph modeling to
      more than 2000 message board posts, and five distinct categories of romantic and
      sexual relationship-related concerns emerged. We conclude that persons with
      epilepsy are at particular risk for the experience of decrements in their
      romantic and sexual relationships, which can negatively impact their self
      management and overall health.

PMID- 28756338
TI  - Patterns of care for ductal carcinoma in situ of the breast: Queensland's
      experience over a decade.
AB  - OBJECTIVES: To review management of ductal carcinoma in situ (DCIS) of the breast
      in Queensland, with reference to breast conserving surgery (BCS) and adjuvant
      radiation therapy (RT). In addition, we examined the incidence of invasive breast
      cancer recurrence and factors predictive of invasive recurrence. MATERIALS AND
      METHODS: A retrospective review of the Queensland Oncology Repository identified
      women with resected DCIS (TisN0) +/- adjuvant RT between 2003 and 2012. Time to
      invasive breast cancer recurrence was analysed using the Kaplan Meier method.
      Median follow-up was 4.9 years. RESULTS: 3038 women had surgery. 940 (31%) had
      mastectomy and 2098 (69%) underwent BCS. Of 2098 women having BCS, 1100 (52%)
      received BCS alone and 998(48%) received adjuvant RT. The use of RT significantly
      increased over the decade from 25% to 62% (p=<0.001). Clinicopathological factors
      associated with RT use on multivariate analysis included age <=70, higher
      socioeconomic status, larger tumour size, higher nuclear grade and surgical
      margins <=5 mm. Invasive breast cancer recurrence at 5 years was 1.7% [95% CI 1.0
      3.0] in RT group versus 2.8% [95% CI 2.1-3.8] in BCS alone group. Factors
      associated with increased risk of invasive recurrence on multivariate analysis
      were age <40 and surgical margins <=2 mm. CONCLUSION: The use of adjuvant RT in
      Queensland significantly increased between 2003 and 2012. Selection of patients
      for RT was based on clinicopathological factors associated with higher recurrence
      risk. Although longer follow-up is required, the selective use of radiation
      therapy after BCS is associated with a low rate of invasive breast cancer
      recurrence at 5 years.

PMID- 28756339
TI  - Whole body MRI for systemic staging of breast cancer in pregnant women.
AB  - When breast cancer is diagnosed during pregnancy, treatment should be as close;
      as possible to what is used in non-pregnant patients. This requires accurate
      local and systemic staging: ultrasound (US) is used for local staging and allows
      adequate evaluation of the liver and pelvis, but chest and bones cannot be
      explored and imaging techniques involving exposure to ionizing radiation would be
      needed. However, since imaging techniques involving ionizing radiation and the
      use of radionuclides should be limited, whole body magnetic resonance imaging (WB
      MRI) without administration of contrast agent represents a very interesting
      alternative, but limited data is available. In this paper we describe the
      obstetrical and oncological outcome of 14 patients in whom breast cancer was
      diagnosed during the second or third trimester of pregnancy and that were staged
      using WB-MRI. Median age of the patient at diagnosis was 35 years (range 20-36),
      median gestational age at MRI was 30 weeks (range 13-32) and median age at
      delivery was 38 weeks (range 32-38). At birth, one new-born presented respiratory
      distress syndrome and one jaundice. We conclude that diffusion-weighted MRI is
      feasible accurate and safe for the mother and for the foetus. It may represent
      the staging technique of choice in pregnant women diagnosed with breast cancer
      after the first trimester of pregnancy.

PMID- 28756340
TI  - A multiplexed screening method for pluripotency.
AB  - Measurement of Alkaline Phosphatase (ALP) level is a widely used procedure in
      clinical and basic research. We present a simple and inexpensive luminescence
      based method that allows multiplexed measurement and normalization of
      intracellular ALP levels in one sample well. The method comprises two
      commercially available reagents enabling quantification of ALP levels and cell
      number by two sequential luminescence readouts. Using this method we were able to
      detect and analyze somatic reprogramming into pluripotent stem cells. The method
      is highly applicable for High Throughput Screening (HTS) campaigns and analysis.

PMID- 28756341
TI  - Once upon a (slow) time in the land of recurrent neuronal networks....
AB  - The brain must both react quickly to new inputs as well as store a memory of past
      activity. This requires biology that operates over a vast range of time scales.
      Fast time scales are determined by the kinetics of synaptic conductances and
      ionic channels; however, the mechanics of slow time scales are more complicated.
      In this opinion article we review two distinct network-based mechanisms that
      impart slow time scales in recurrently coupled neuronal networks. The first is in
      strongly coupled networks where the time scale of the internally generated
      fluctuations diverges at the transition between stable and chaotic firing rate
      activity. The second is in networks with finitely many members where noise
      induced transitions between metastable states appear as a slow time scale in the
      ongoing network firing activity. We discuss these mechanisms with an emphasis on
      their similarities and differences.

PMID- 28756342
TI  - Metal ion - Dehydrin interactions investigated by affinity capillary
      electrophoresis and computer models.
AB  - Dehydrins are specialized proteins which are related to environmental stress
      tolerance in plants. The proteins can bind different metal ions and have
      versatile other functions such as reduction of reactive oxygen species and acting
      as transcription factor. The structure determination of proteins from this family
      is challenging, since they have a high number of disordered structure elements.
      Consequently, to determine the functionality of these proteins on a molecular
      basis a computed model is helpful. This work focuses on a model for the
      Arabidopsis thaliana dehydrin AtHIRD11. To develop a model which reflects
      experimental data from literature and own binding data from affinity capillary
      electrophoresis experiments, a more rigid state of this protein was chosen. The
      Cu2+-complex of this protein was formed and evaluated. The model explains some of
      the properties of the complexes. Possible Cu2+-bindings site were found and the
      change of conformations were investigated via molecular dynamics simulation. The
      AtHIRD11-Cu2+-complex is a first approach towards a complex model for a
      structural versatile protein, which is already sufficient to explain binding data
      and possible structure elements.

PMID- 28756343
TI  - PTSD symptoms are associated with visual retrieval performance in OEF/OIF/OND
      veterans.
AB  - Posttraumatic stress disorder (PTSD) is associated with poorer performance on
      neuropsychological tests in veterans. However, prior studies have generally
      compared individuals with PTSD to control groups, often excluding individuals
      with moderate symptoms. The present study evaluated neuropsychological
      performance among OEF/OIF/OND veterans as a function of overall PTSD severity,
      while also exploring potential associations between cognitive performance and
      PTSD symptom clusters. Using a brief neuropsychological battery, clinical
      interviews, and self-report instruments, we evaluated neuropsychological and
      psychiatric functioning in 90 OEF/OIF/OND veterans. When controlling for the
      effects of premorbid intellectual functioning and combat exposure, higher PTSD
      severity predicted worse visual retrieval performance, but not attention, verbal
      retrieval, visual learning, or executive functioning performance. A trend was
      observed where higher PTSD symptoms predicted worse verbal learning performance.
      All PTSD symptom clusters were associated with visual retrieval performance
      within the full sample. Avoidance and numbing symptoms were associated with
      verbal learning in the full sample. Findings suggest that among OEF/OIF/OND
      veterans with a range of PTSD symptoms, the assessment of visual memory may have
      implications for clinical practice.

PMID- 28756344
TI  - Development of a reliable experimental set-up for Dover sole larvae Solea solea
      L. and exploring the possibility of implementing this housing system in a
      gnotobiotic model.
AB  - Due to the increasing importance of the aquaculture sector, diversification in
      the number of cultured species imposes itself. Dover sole Solea solea L. is put
      forward as an important new aquaculture candidate due to its high market value
      and high flesh quality. However, as for many other fish species, sole production
      is hampered by amongst others high susceptibility to diseases and larval
      mortality, rendering the need for more research in this area. In this respect, in
      first instance, a housing system for Dover sole larvae was pinpointed by keeping
      the animals individually in 24-well plates for 26days with good survival rates
      and initiating metamorphosis. This ensures a standardised and reliable
      experimental set-up in which the possible death of one larva has no effect on the
      other larvae, rendering experiments adopting such a system more reproducible. In
      addition to proving valuable in many other applications, this multi well system
      constitutes a firm basis to enable the gnotobiotic rearing of larvae, which
      hitherto is non-existing for Dover sole. In this respect, secondly, a large
      number of disinfection protocols were tested, making use of widely employed
      disinfectants as hydrogen peroxide, glutaraldehyde and/or ozone whether or not
      combined with a mixture of antimicrobial agents for 24h. Although none of the
      tested protocols was sufficient to reproducibly generate a gnotobiotic model, the
      combination of glutaraldehyde and hydrogen peroxide resulted in hatchable,
      bacteria-free eggs in some cases.

PMID- 28756345
TI  - Gait alterations in the UAE population with and without diabetic complications
      using both traditional and entropy measures.
AB  - Diabetic foot, one of the most common and debilitating manifestations of type 2
      diabetes mellitus (T2DM), is the leading cause of worldwide non-traumatic lower
      extremity amputations. Diabetics who are at risk of ulceration are currently
      mainly identified by a thorough clinical examination of the feet, which typically
      does not show clear symptoms during the early stages of disease progression. In
      this study, we used a non-linear dynamics tool, gait entropy (GaitEN), in
      addition to traditional linear gait analysis methods, to investigate gait
      alterations amongst diabetic patients with combinations of three types of T2DM
      related complications: retinopathy, diabetic peripheral neuropathy (DPN) and
      nephropathy. Peak plantar pressure (PPP) was not significantly different in the
      group with DPN as compared to the control group (diabetics with no complications,
      CONT) in the forefoot region (DPN: mean+/-SD: 396+/-69.4kPa, CONT: 409+/
      68.9kPa), although it was significantly lower in the heel region (DPN: mean+/-SD:
      285+/-43.1.4kPa, CONT: 295+/-61.8kPa). On the other hand, gait entropy was
      significantly lower for the DPN compared to CONT group (DPN: 0.95+/-0.34, CONT:
      1.03+/-0.28, p<0.05). The significant low entropy was maintained when neuropathy
      was combined with either retinopathy or nephropathy. For the group with all three
      complications (ALL-C), the entropy was higher than CONT (ALL-C: 1.07+/-0.26).
      This may indicate an intrinsic sensorimotor feedback mechanism for the DPN
      patients to regulate their gait. However, this feedback gets weaker as patients
      develop multiple complications. Further analysis with longer walking time and
      different speeds is needed to verify the entropy results.

PMID- 28756346
TI  - Plant growth and resistance promoted by Streptomyces spp. in tomato.
AB  - Plant Growth Promoting Rhizobacteria (PGPR) represent an alternative to improve
      plant growth and yield as well as to act as agents of biocontrol. This study
      characterized isolates of Streptomyces spp. (Stm) as PGPR, determined the
      antagonism of these isolates against Pectobacterium carotovorum subsp.
      brasiliensis (Pcb), evaluated the ability of Stm on promoting growth and
      modulating the defense-related metabolism of tomato plants, and the potential of
      Stm isolates on reducing soft rot disease in this species. The VOC profile of Stm
      was also verified. Promotion of plant growth was assessed indirectly through VOC
      emission and by direct interaction with Stm isolates in the roots. Evaluation of
      soft rot disease was performed in vitro on plants treated with Stm and challenged
      with Pcb. Enzymes related to plant defense were then analyzed in plants treated
      with three selected isolates of Stm, and PM1 was chosen for further Pcb
      challenging experiment. Streptomyces spp. isolates displayed characteristics of
      PGPR. PM3 was the isolate with efficient antagonism against Pcb by dual-culture.
      Most of the isolates promoted growth of root and shoot of tomato plants by VOC,
      and PM5 was the isolate that most promoted growth by direct interaction with Stm.
      Soft rot disease and mortality of plants were significantly reduced when plants
      were treated with StmPM1. Modulation of secondary metabolism was observed with
      Stm treatment, and fast response of polyphenoloxidases was detected in plants
      pretreated with StmPM1 and challenged with Pcb. Peroxidase was significantly
      activated three days after infection with Pcb in plants pretreated with StmPM1.
      Results suggest that Streptomyces sp. PM1 and PM5 have the potential to act as
      PGPR.

PMID- 28756347
TI  - Wheat and rye genome confer specific phytohormone profile features and interplay
      under water stress in two phenotypes of triticale.
AB  - The aim of the experiment was to determine phytohormone profile of triticale and
      quality-based relationships between the analyzed groups of phytohormones. The
      study involved two triticale phenotypes, a long-stemmed one and a semi-dwarf one
      with Dw1 gene, differing in mechanisms of acclimation to drought and controlled
      by wheat or rye genome. Water deficit in the leaves triggered a specific
      phytohormone response in both winter triticale phenotypes attributable to the
      dominance of wheat (semi-dwarf cultivar) or rye (long-stemmed cultivar) genome.
      Rye genome in long-stemmed triticale was responsible for specific increase
      (tillering: gibberellic acid; heading: N6-isopentenyladenine, trans-zeatin-9
      riboside, cis-zeatin-9-riboside; flowering: N6-isopentenyladenine, indolebutyric
      acid, salicylic acid) or decrease (heading: trans-zeatin) in the content of some
      phytohormones. Wheat genome in semi-dwarf triticale controlled a specific
      increase in trans-zeatin content at heading and anthesis in gibberellin A1 during
      anthesis. The greatest number of changes in the phytohormone levels was observed
      in the generative phase. In both triticale types, the pool of investigated
      phytohormones was dominated by abscisic acid and gibberellins. The semi-dwarf
      cultivar with Dw1 gene was less sensitive to gibberellins and its mechanisms of
      acclimation to water stress were mainly ABA-dependent. An increase in ABA and
      gibberellins during drought and predominance of these hormones in the total pool
      of analyzed phytohormones indicated their equal share in drought acclimation
      mechanisms in long-stemmed cultivar.

PMID- 28756349
TI  - Interrater agreement in visual scoring of neonatal seizures based on majority
      voting on a web-based system: The Neoguard EEG database.
AB  - OBJECTIVE: To assess interrater agreement based on majority voting in visual
      scoring of neonatal seizures. METHODS: An online platform was designed based on a
      multicentre seizure EEG-database. Consensus decision based on 'majority voting'
      and interrater agreement was estimated using Fleiss' Kappa. The influences of
      different factors on agreement were determined. RESULTS: 1919 Events extracted
      from 280h EEG of 71 neonates were reviewed by 4 raters. Majority voting was
      applied to assign a seizure/non-seizure classification. 44% of events were
      classified with high, 36% with moderate, and 20% with poor agreement, resulting
      in a Kappa value of 0.39. 68% of events were labelled as seizures, and in 46%,
      all raters were convinced about electrographic seizures. The most common seizure
      duration was <30s. Raters agreed best for seizures lasting 60-120s. There was a
      significant difference in electrographic characteristics of seizures versus
      dubious events, with seizures having longer duration, higher power and amplitude.
      CONCLUSIONS: There is a wide variability in identifying rhythmic ictal and non
      ictal EEG events, and only the most robust ictal patterns are consistently agreed
      upon. Database composition and electrographic characteristics are important
      factors that influence interrater agreement. SIGNIFICANCE: The use of well
      described databases and input of different experts will improve neonatal EEG
      interpretation and help to develop uniform seizure definitions, useful for
      evidence-based studies of seizure recognition and management.

PMID- 28756348
TI  - Measuring alterations in oscillatory brain networks in schizophrenia with resting
      state MEG: State-of-the-art and methodological challenges.
AB  - OBJECTIVE: Neuroimaging studies provide evidence of disturbed resting-state brain
      networks in Schizophrenia (SZ). However, untangling the neuronal mechanisms that
      subserve these baseline alterations requires measurement of their
      electrophysiological underpinnings. This systematic review specifically
      investigates the contributions of resting-state Magnetoencephalography (MEG) in
      elucidating abnormal neural organization in SZ patients. METHOD: A systematic
      literature review of resting-state MEG studies in SZ was conducted. This
      literature is discussed in relation to findings from resting-state fMRI and EEG,
      as well as to task-based MEG research in SZ population. Importantly,
      methodological limitations are considered and recommendations to overcome current
      limitations are proposed. RESULTS: Resting-state MEG literature in SZ points
      towards altered local and long-range oscillatory network dynamics in various
      frequency bands. Critical methodological challenges with respect to experiment
      design, and data collection and analysis need to be taken into consideration.
      CONCLUSION: Spontaneous MEG data show that local and global neural organization
      is altered in SZ patients. MEG is a highly promising tool to fill in knowledge
      gaps about the neurophysiology of SZ. However, to reach its fullest potential,
      basic methodological challenges need to be overcome. SIGNIFICANCE: MEG-based
      resting-state power and connectivity findings could be great assets to clinical
      and translational research in psychiatry, and SZ in particular.

PMID- 28756350
TI  - Immunotherapy in adult acute leukemia.
AB  - The treatment of acute myeloid leukemia (AML) did not evolve profoundly in the
      last decades. Some improvement has been made for acute lymphoblastic leukemia
      (ALL). Emerging new treatment modalities, such as immunotherapy, are now
      beginning to be available for acute leukemia, mostly for patients suffering from
      ALL. This review aims to give an overview of these new therapeutic approaches,
      especially those already available. The focus is on cell-based immunotherapy, or
      molecules using preexisting host cells. Underlying mechanisms are explained and
      an overview of clinical experience with phase 1-3 studies is given.
      Immunotherapies discussed are antibody-drug conjugates, bispecific T-cell
      engagers (BiTEs), chimeric antigen receptor T cells (CARTs) and immune checkpoint
      inhibitors (ICPIs). Most of the clinical studies reviewed are in ALL patients,
      usually in the relapse setting, but where available, studies on AML patients were
      also considered. This new general treatment approach offers hope to patients with
      until now dismal clinical outcome. Hopes are high that future developments, and
      moving these therapies to an earlier treatment phase, will improve the prognosis
      of patients suffering from acute leukemia.

PMID- 28756351
TI  - Linguistic generalization on the basis of function and constraints on the basis
      of statistical preemption.
AB  - How do people learn to use language in creative but constrained ways? Experiment
      1 investigates linguistic creativity by exposing adult participants to two novel
      word order constructions that differ in terms of their semantics: One
      construction exclusively describes actions that have a strong effect; the other
      construction describes actions with a weaker but otherwise similar effect. One
      group of participants witnessed novel verbs only appearing in one construction or
      the other, while another group witnessed a minority of verbs alternating between
      constructions. Subsequent production and judgment results demonstrate that
      participants in both conditions extended and accepted verbs in whichever
      construction best described the intended message. Unlike related previous work,
      this finding is not naturally attributable to prior knowledge of the likely
      division of labor between verbs and constructions or to a difference in cue
      validity. In order to investigate how speakers learn to constrain
      generalizations, Experiment 2 includes one verb (out of 6) that was witnessed in
      a single construction to describe both strong and weak effects, essentially
      statistically preempting the use of the other construction. In this case,
      participants were much more lexically conservative with this verb and other
      verbs, while they nonetheless displayed an appreciation of the distinct semantics
      of the constructions with new novel verbs. Results indicate that the need to
      better express an intended message encourages generalization, while statistical
      preemption constrains generalization by providing evidence that verbs are
      restricted in their distribution.

PMID- 28756352
TI  - Resolving uncertainty in plural predication.
AB  - Plural predications (e.g., "the boxes are heavy") are common sources of ambiguity
      in everyday language, allowing both distributive and collective interpretations
      (e.g., the boxes each are heavy vs. the boxes together are heavy). This paper
      investigates the role of context in the disambiguation of plural predication. We
      address the key phenomenon of "stubborn distributivity," whereby certain
      predicates (e.g., big, tall) are claimed to lack collective interpretations
      altogether. We first validate a new methodology for measuring the interpretation
      of plural predications. Using this method, we then analyze naturally-occurring
      plural predications from corpora. We find a role of context, but no evidence of a
      distinct class of predicates that resists collective interpretations. We further
      explore the role of context in our final experiments, showing that both the
      predictability of properties and the knowledgeability of the speaker affect
      disambiguation. This suggests a pragmatic account of how ambiguous plural
      predications are interpreted. In particular, stubbornly distributive predicates
      are so because the collective properties they name are unpredictable, or
      unstable, in most contexts; this unpredictability results in a noisy collective
      interpretation, something speakers and listeners recognize as ineffective for
      communicating efficiently about their world. We formalize the pragmatics of
      utterance disambiguation within the Bayesian Rational Speech Act framework.

PMID- 28756353
TI  - A birth cohort study of Asian and Pacific Islander children reported for abuse or
      neglect by maternal nativity and ethnic origin.
AB  - Research identifying racial and ethnic disparities in child protective services
      (CPS) involvement in the U.S. has focused on the overrepresentation of Black
      children and the growing Latino child population. Little attention has been paid
      to children of Asian origin, the most underrepresented group of children in the
      U.S. CPS system. The objective of this analysis was to examine subgroup patterns
      of CPS involvement in California for Asian and Pacific Islander (API) children
      prospectively based on maternal nativity and ethnic origin. We extracted data for
      API children born in California in 2006 and 2007 (N=138,858) from population
      based birth records and linked those records to CPS records spanning the first 5
      years of life (through 2012). We assessed distributional differences in risk
      indicators for the full birth cohort of API children and calculated a summary
      risk variable representing the cumulative number of risks present at birth.
      Generalized linear models were used to estimate API children's adjusted relative
      risk of CPS report by subgroup. Overall, 12.2% of children born in California in
      the 2006-2007 birth cohort were API. The majority of API children had foreign
      born mothers (80.9%). Children of U.S.-born Hawaiian, Guamanian, or Samoan
      mothers had the highest rate, with 20.4% being reported to CPS by their 5th
      birthday. The lowest rates of child abuse and neglect reporting were observed
      among children of foreign-born Asian Indian (2.5%), Korean (2.7%), and Chinese
      (2.8%) mothers, compared to 5.4% of all Asian and Pacific Islander children, and
      14.8% of children in general population. Findings underscore the presence of
      disparities in CPS involvement among API children, which has implications for
      health and well-being across the life course and for targeted maltreatment
      prevention strategies.

PMID- 28756354
TI  - A latent class analysis of poly-marijuana use among young adults.
AB  - INTRODUCTION: With more states legalizing marijuana use, the marijuana industry
      has grown, introducing a variety of marijuana products. Our study explores the
      use of multiple marijuana products (poly-marijuana use) and the characteristics
      associated with this behavior. METHODS: Past-month marijuana users aged 18
      34years were surveyed online via an existing online panel (n=2444). Participants
      answered questions about past-month use of three types of marijuana (plant-based,
      concentrates, edibles), marijuana use patterns, and driving after use. Latent
      class analysis was used to identify subgroups of marijuana users. RESULTS: Four
      classes of marijuana users were identified: Light plant users, who used only
      plant-based products infrequently and were unlikely to drive after use (32%);
      Heavy plant users, who used mainly plant-based products frequently, multiple
      times per day, and were likely to drive after use (37%); Plant and concentrates
      users, who used plant-based products heavily and concentrates at least
      infrequently, used multiple times per day, and were likely to drive after use
      (20%); Light plant and edibles users, who used both products infrequently and
      were unlikely to drive after use (10%). Those in legal marijuana states were more
      likely to belong to the poly-marijuana groups. DISCUSSION: Our findings reflect
      the increase in popularity of new marijuana products in legal states and suggest
      that heavy user groups, including concentrates users, are associated with driving
      after use. As various forms of marijuana use increases, monitoring and
      surveillance of the use of multiple types of marijuana will be important for
      determining potential varying impacts on physiological and social consequences.

PMID- 28756355
TI  - A validated HPLC-UV method for the analysis of galloylquinic acid derivatives and
      flavonoids in Copaifera langsdorffii leaves.
AB  - Copaifera langsdorffii Desf. (Fabaceae, Caesalpinioideae), popularly known as
      "copaiba" or "pau d'oleo", is a species of tree that is found throughout Brazil.
      The leaves of this tree are used in folk medicine to treat kidney stones.
      Galloylquinic acid derivatives and flavonoids are the main secondary metabolites
      found in C. langsdorffii leaves and are likely to be responsible for the
      effectiveness of this treatment. As an attempt to produce a phytotherapic, we
      have developed a reliable HPLC-UV method for the quality control of C.
      langsdorffii leaves. Phenolic compounds were extracted from C. langsdorffii
      leaves using 70% aqueous ethanol as the extraction solvent. HPLC-UV analyses were
      carried out on a Synergi Polar-RP column (100*3.0mm, 2.5MUm), and the mobile
      phase was made up of formic acid-water (0.1:99.9, solvent A), and isopropanol
      methanol-acetonitrile (5:40:60, solvent B). The elution gradient was A:B (90:10
      to 85:15) in 8.0min, followed by A:B (85:15 to 64:36) up to 30.0min, using a flow
      rate of 0.7mL/min, and UV detection at 280nm. This method was used to quantify
      nine galloylquinic acid derivatives and two flavonoids, which gave a good
      detection response and linearity in the range of 1.88-110.0MUg/mL. Furthermore,
      the detection and quantification limits ranged from 0.070 to 0.752MUg/mL, and
      0.211-2.278MUg/mL respectively, with a maximum RSD of 4.18%. The method is
      reliable for the quality control of C. langsdorffii raw material, its
      hydroethanolic extract, and could potentially be used to quantify these compounds
      in other Copaifera species.

PMID- 28756356
TI  - Comparative pharmacokinetics of six major bioactive components in normal and type
      2 diabetic rats after oral administration of Sanhuang Xiexin Decoction extracts
      by UPLC-TQ MS/MS.
AB  - A rapid, sensitive, and selective UPLC-TQ-MS/MS method was established and
      validated for the determination and pharmacokinetic investigation of rhein,
      coptisine, berberine, palmatine, baicalin and wogonoside from Sanhuang Xiexin
      Decoction (SXD) extracts. A Waters BEH C18 UPLC column was used with the mobile
      phases of Acetonitrile-0.1% formic acid-water. The lower limits of quantification
      (LLOQ) for rhein, coptisine, berberine, palmatine, baicalin and wogonoside were
      24.16, 0.72, 0.68, 0.53, 18.07 and 28.56ng/mL, respectively. All calibration
      curves displayed good linearity (r2>0.995). The precision was evaluated by intra
      day and inter-day assays and the RSD% were all within 9.12%, and the bias of the
      accuracies ranged from -7.50% to 8.03%. The recovery ranged from 74.83% to 94.32%
      and the matrix effects of six analytes were found to be between 90.17% and
      103.10%. The stability study showed that compounds were stable during the
      experiment. Finally, the data showed that the pharmacokinetic (PK) profiles
      (especially AUC, Tmax and Cmax) of six analytes in diabetic rats were
      significantly diverse from that in normal group rats. The PK study under the
      pathological condition could provide more helpful information to guide the
      clinical usage of SXD to treat T2DM.

PMID- 28756357
TI  - High-performance liquid chromatography with time-programmed fluorescence
      detection for the quantification of Levofloxacin in human plasma and
      cerebrospinal fluid in adults with tuberculous meningitis.
AB  - An accurate and reliable high-performance liquid chromatography with time
      programmed fluorescence detection was developed and validated to measure
      levofloxacin in human plasma and cerebrospinal fluid (CSF). After solid phase
      extraction process using Evolute(r) ABN 96 fixed well plate; levofloxacin and
      internal standard-enoxacin were separated using a mobile phase consisting of
      phosphate buffer 10mM with 0.025% triethylamine pH 3.0 - acetonitrile (88:12,
      v/v) on a Purosphere RP-8e column (5MUm, 125*4.0mm) at a flow rate of 1.2mL/min
      at 35 degrees C. The excitation/emission wavelengths were set to 269/400nm and
      294/500nm, for enoxacin and levofloxacin, respectively. The method was linear
      over the concentration range of 0.02 to 20.0MUg/mL with a limit of detection of
      0.01MUg/mL. The relative standard deviation of intra-assay and inter-assay
      precision for levofloxacin at four quality controls concentrations (0.02, 0.06,
      3.0 and 15.0MUg/mL) were less than 7% and the accuracies ranged from 96.75% to
      101.9% in plasma, and from 93.00% to 98.67% in CSF. The validated method was
      successfully applied to quantify levofloxacin in a considerable quantity of
      plasma (826) and CSF (477) samples collected from 232 tuberculous meningitis
      patients, and the preliminary intensive pharmacokinetics analysis from 14
      tuberculous meningitis patients in Vietnam is described in this paper.

PMID- 28756358
TI  - Jejunal diverticula with perforation in non steroidal anti inflammatory drug
      user: A case report.
AB  - INTRODUCTION: Multiple diverticulosis of the jejunum constitutes an uncommon
      pathology of the small bowel. The disease is often asymptomatic and must be taken
      into consideration in cases of unexplained malabsorption, anemia, chronic
      abdominal pain and discomfort. CASE PRESENTAION: We are thereby reporting a 50yr
      patient on chronic NSAID ingestion presenting to us with acute abdomen. On
      exploration, there were multiple (14) jejunal diverticuli on both mesenteric and
      antimesentric border from 10cm to 90cm distal to duedenojejunal junction with a
      perforation in one of the diverticulum, 80cm distal to the ligament of Treitz. We
      performed a resection of a 80-cm jejunal segment involving the multiple
      diverticula and an end to end jejunojejunostomy. DISCUSSION: Drug-induced jejunal
      perforation is known, but jejunal diverticular perforation related to
      steroid/treatment has been reported only once previously. Long-term NSAID therapy
      usually induces clinically silent enteropathy characterized by increased
      intestinal permeability and inflammation. Jejunal diverticulosis is a challenging
      disorder from a diagnostic perspective, with no truly reliable diagnostic tests.
      The current treatment of choice for perforated jejunal diverticula causing
      generalized peritonitis is prompt laparotomy with segmental intestinal resection
      and primary anastomosis. CONCLUSION: Jejunal diverticula are rare lesions, and
      their perforation never features in the list of diagnoses for acute abdomen,
      especially in this part of the world. Further this unique case report opens the
      doors for further research to prove an assosiation between NSAID use and
      diverticular perforation which itself is a very rare entity.

PMID- 28756359
TI  - Post-transplant lymphoproliferative disorder and management of residual mass post
      chemotherapy: Case report.
AB  - INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a rare
      complication. It represents a spectrum of lymphoid proliferations which occur in
      the setting of immunosuppression and organ transplantation. There are no reported
      cases or recommendations for the treatment of residual masses post rituximab of
      PTLD. PRESENTATION OF CASE: A patient with a long standing history of
      immunosuppression due to multiple kidney transplants starting in 1979, presented
      with a very large palpable hard abdominal mass (2004) after a fourth renal
      transplant. There was a past history of heavy immune suppression. CT scans
      revealed a conglomerate mass involving the right native kidney and two prior
      right sided renal allografts that crossed the midline. Biopsy of the large right
      retroperitoneal mass revealed large B cell lymphoma (CD 20 positive); consistent
      with post-transplant lymphoproliferative disorder (PTLD). DISCUSSION: Management
      of bulky PTLD, in a highly sensitized, heavily immune suppressed patient is not
      well described in the literature. The mainstay of therapy is IR and Ritixumab (R)
      monotherapy and combination R-CHOP. CHOP chemotherapy has an associated mortality
      rate of up to 38%. Radiotherapy is often considered over surgery and surgery has
      been most frequently used when associated with bowel complications. In this case
      report we describe upfront Ritiximab followed by consolidation resection and
      cytotoxic chemotherapy as a management strategy to reduce toxicity. CONCLUSION:
      The approach taken by our surgical team illustrates the benefits of disease
      debulking in certain cases of PTLD, by guiding further therapy and spacing and
      reducing chemotherapy in immune suppressed patients.

PMID- 28756360
TI  - Combined intra- and extraperitoneal urinary bladder rupture - a rare seat-belt
      injury: A case report.
AB  - INTRODUCTION: While isolated traumatic urinary bladder injuries are rare,
      combined intra- and extraperitoneal traumatic urinary bladder ruptures without an
      underlying fracture are an absolute rarity. PRESENTATION OF CASE: We report a
      case of combined intra- and extraperitoneal urinary bladder rupture without an
      underlying fracture resulting from blunt abdominal trauma during a high velocity
      car accident. A midline laparotomy was performed, and the intra- and
      extraperitoneal bladder ruptures were surgically treated. DISCUSSION: Based on
      the presented case the anatomical peculiarities of the urinary bladder and the
      different trauma mechanisms as well as the resulting lesions, the diagnostic
      modalities and the treatment options are discussed. CONCLUSION: Despite the
      rarity of traumatic urinary bladder injuries, and especially in the absence of an
      underlying fracture, physicians should maintain a high level of suspicion for
      urologic injuries in the presence of nonspecific lower abdominal pain, gross
      haematuria and the inability to urinate.

PMID- 28756361
TI  - A case of single incision laparoscopic total colectomy for intestinal neuronal
      dysplasia type B.
AB  - INTRODUCTION: Intestinal neuronal dysplasia type B (IND-B) is an infrequent
      disease of the submucosal plexus of intestine manifesting chronic intestinal
      obstruction or severe chronic constipation. IND is rarely reported in adult
      patients. PRESENTATION OF A CASE: The present study reports on the case of a 36
      year-old woman suffering from longstanding chronic constipation and who was
      diagnosed with severe constipation in more than 20 years. Although she began to
      take a large amount of stimulant laxatives, such as "senna" and "bisacodyl",
      constipation symptoms did not improve, she was admitted to our hospital. It was
      diagnosed with refractory constipation of the medication treatment-resistance,
      total colectomy with ileorectal anastomosis by single incision laparoscopic
      surgery (SILS) was performed. The final pathological diagnosis was IND-B.
      DISCUSSION: Refractory constipation after medical treatment is often seen in
      young generation. SILS has benefits of better cosmesis, reduced morbidity,
      reduced postoperative pain, and reduced length of hospital stay. CONCLUSION: For
      the patients with refractory constipation associated with neuropathy such as IND,
      total colectomy by SILS was very effective.

PMID- 28756362
TI  - Massive bleeding after a tooth extraction: Diagnosis of unknown arteriovenous
      malformation of the mandible, a case report.
AB  - INTRODUCTION: Arteriovenous malformations (AVMs) are very rare. Only 5% of them
      occurs in the jaws but they can manifest with dramatic bleeding and be life
      threatening. PRESENTATION OF CASE: We report the case of a 11-year-old healthy
      girl who presented a massive hemorrhage after extraction of the right mandibular
      first primary molar. This patient received a blood transfusion and was
      hospitalized in pediatric intensive care unit. CT angiography highlighted an AVM
      of the mandible. Treatment consisted in selective embolization. DISCUSSION: A
      review of the literature shows that the majority of AVMs of the jaws are often
      unknown until severe bleeding occurs during dental surgery. The low specificity
      of radiological signs on panoramic radiography makes the diagnosis particularly
      challenging. Their management requires an interdisciplinary approach. Selective
      embolization has a place of choice in the treatment of these complex pathologies.
      CONCLUSION: Although AVMs of the jaws are rare, they are frequently revealed
      through a massive hemorrhage during tooth extraction. Dentists have to suspect
      them when young patients present some clinical features, as spontaneous gingival
      bleeding, unexplained dental mobility, or facial asymmetry.

PMID- 28756363
TI  - Torsion of huge wandering accessory spleen. Case report and review of literature.
AB  - INTRODUCTION: Accessory spleens are found in 10-15% of the population, and are
      even more prevalent in patients with hematological disorders (Rudowski, 1985). It
      infrequently may become symptomatic due to torsion, spontaneous rupture or
      hemorrhage which may lead to death. Torsion of an accessory spleen is extremely
      rare, and requires prompt medical attention [2] (Coote et al., 1999).
      PRESENTATION OF CASE: We report the case of a 27-year-old Mediterranean lady with
      thalassemia trait, who presented to the emergency department with an acute
      surgical abdomen due to torsion of a giant accessory spleen, measuring 13cm. She
      was diagnosed with the aid of ultrasound and computed tomography (CT) scan and
      was treated surgically through resection of the spleen. DISCUSSION AND
      CONCLUSION: Torsion of an accessory spleen is not common, and is the surgical
      indication in about 0.2-0.3% of splenectomies (Mortele et al., 2004). It has
      variable clinical presentations, and is a difficult preoperative diagnosis due to
      lack of specificity of symptoms. Accessory spleens are usually smaller than 3cm,
      with few cases being reported as larger than 10cm larger accessory spleens have a
      higher rate of torsion. Knowledge of this pathology, and familiarity with its
      radiological findings are fundamental to accurately diagnosing and manageming
      this challenging condition.

PMID- 28756364
TI  - Chiari I malformation with underlying pseudotumor cerebri: Poor symptom relief
      following posterior decompression surgery.
AB  - INTRODUCTION: ? Pseudotumor cerebri (PTC) patients exhibit clear clinical signs
      and symptoms of higher intracranial pressure (ICP) without ventricular
      enlargement or mass lesions. The clinical picture of patients with PTC can
      sometimes be similar to that of Chiari Malformation type I (CMI). There is some
      evidence that Chiari I malformation and PTC may coexist, which raises the
      question of whether PTC is an idiopathic disease or a complication of posterior
      decompression surgery-treatment of choice for Chiari I malformation. PRESENTATION
      OF CASES: A retrospective review of electronic medical records of patients
      diagnosed with PTC at the University of Toledo Medical Center (UTMC) was
      performed. The objective was to determine whether PTC patients had a concurrent
      diagnosis of Chiari I malformation and whether the diagnosis of PTC occurred
      before or after posterior decompression surgery. Out of the 8 eligible patient
      medical records reviewed, 5 patients diagnosed with PTC had undergone posterior
      decompression surgery for Chiari I malformation at anywhere from several days to
      three years prior to being diagnosed with PTC. The diagnosis of PTC was based on
      temporary symptomatic relief following lumbar puncture which also showed elevated
      CSF opening pressures. Finally, a VP shunt was placed in each of the 5 patients
      to relieve the elevated intracranial pressure which resulted in the complete
      resolution of the patients' symptoms. DISCUSSION: Our study focuses on patients
      who were diagnosed with and treated for CMI then reported back to the clinic
      within several days to three years complaining of symptoms of headache. Upon re
      presenting to the clinic, a CSF flow study was performed which showed normal flow
      of CSF. Then, these patients underwent a lumbar puncture which demonstrated an
      elevated opening pressure (and ICP) and a temporary relief of the headache with
      lumbar drainage. A VP shunt was placed for each patient to treat for PTC, and the
      patients' headaches were relieved. CONCLUSION: This study suggests that the
      presence of Chiari I malformation in a patient conceals the symptoms of PTC which
      may become apparent following posterior decompression surgery. Other
      possibilities could be that the patients are misdiagnosed for Chiari I
      malformation when they are in fact suffering from PTC, or that PTC is a
      complication of surgery.

PMID- 28756365
TI  - Interaction between 17 alpha-ethynylestradiol hormone with Langmuir monolayers:
      The role of charged headgroups.
AB  - The persistence of steroid hormones disposed of in the environment may pose risks
      to the health of humans and wildlife, which brings the need of understanding
      their mode of action, believed to occur in cell membranes. In this study, we
      investigate the molecular-level interactions between the synthetic hormone 17
      alpha-ethynylestradiol (EE2) and Langmuir monolayers that represent simplified
      cell membranes. In surface pressure isotherms, EE2 was found to expand the
      monolayers at low surface pressures of the positively charged
      dimethyldioctadecylammonium bromide (DODAB), zwitterionic 1,2-dipalmitoyl-sn
      glycerol-3-phosphocholine (DPPC), negatively charged 1,2-dipalmitoyl-sn-glycero-3
      phosphoglycerol (DPPG), and partially anionized stearic acid (StAc). The largest
      effects were observed for the charged DODAB and DPPG. At the pressure (30mN.m-1)
      corresponding to the molecular packing of a cell membrane, EE2 caused the
      compressibility modulus to decrease, again with the largest changes occurring for
      DODAB and DPPG. The effects from EE2 on the packing of the lipid molecules at
      this high pressure depended essentially on the size of the headgroups, with EE2
      contributing to the area per lipid for StAc and DODAB, whose headgroups are
      small. EE2 interacted with the headgroups of all lipids and StAc, also affecting
      the ordering of the tails for DODAB, DPPG and DPPC, according to in situ
      polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS).
      Based on the analysis with the two characterization methods, we propose a model
      for the EE2 positioning and molecular groups involved in the interaction, which
      should be relevant to unveil the endocrine disrupting action of EE2.

PMID- 28756366
TI  - Structure of unsaturated fatty acids in 2D system.
AB  - The behaviour of Langmuir monolayers corresponding to unsaturated fatty acids
      belonging to the omega-9 (oleic acid), omega-3 (alpha-linolenic and stearidonic
      acids) and omega-6 (linoleic, gamma-linolenic and eicosadienoic acids) series was
      studied in order to get insight into the influence of various factors (such as
      subphase temperature, length, degree of unsaturation and position of the double
      bonds in the aliphatic chains) on the molecular conformation of these fatty acids
      spread at the A/W interface. The obtained results derived from the surface
      pressure - area isotherms, compressibility modulus and monolayer thickness prove
      that the lift-off and the limiting areas of investigated films increase both with
      the number of double bonds and length of the hydrocarbon chain. Also, the
      monolayers are more compressible (more fluid) upon increasing their tails
      unsaturation degree. However, eicosadienoic (EA) film is more rigid due to its
      longer acyl chain. Polyunsaturated fatty acids (PUFAs) monolayers, except for EA,
      exhibit anomalous temperature dependence (area contraction with increasing
      temperature), which was attributed to the increased solubility of PUFAs molecules
      with temperature. The recorded thickness values of the monolayers were compared
      with those estimated from theoretical molecular conformations in order to
      establish the orientation and configuration of molecules in different surface
      states of their monolayer.

PMID- 28756367
TI  - The participation of oxidative stress in the pathogenesis of bronchial asthma.
AB  - Reactive oxygen species are produced during oxygen reduction and are
      characterized by high reactivity. They participate in many important
      physiological processes, but if produced in high concentrations they lead to
      oxidative stress development and disturb pro-oxidative/anti-oxidative balance
      towards the oxidation reaction - leading to damage of lipids, proteins,
      carbohydrates or nucleic acids. Asthma is a chronic inflammatory disease of the
      airways of various pathogenesis and clinical symptoms, prevalence in recent years
      has increased significantly. Recently published literature point out the
      involvement of reactive oxygen species in the pathogenesis of asthma. Changes in
      the protein and lipid oxidation lead, among others, to pathological changes in
      the respiratory epithelial cells, an increase in vascular permeability, mucus
      overproduction, smooth muscle contraction or airway hyperresponsiveness (AHR).
      The aim of this study is to present the current state of knowledge on the
      influence of oxidative stress parameters on asthma development.

PMID- 28756368
TI  - Cadmium chloride-induced testicular toxicity in male wistar rats; prophylactic
      effect of quercetin, and assessment of testicular recovery following cadmium
      chloride withdrawal.
AB  - This study assessed the effect of quercetin (QE) on cadmium chloride (CdCl2) -
      induced testicular toxicity, as well as the effect of withdrawal of CdCl2
      treatment on same. Thirty male Wistar rats aged 10 weeks old and weighing 270
      300g were assigned into 5 groups and used for this study. Rats in groups 1-4 were
      administered vehicle, CdCl2 (5mg/kg bwt), CdCl2+QE (5mg/kg bwt and 20mg/kg bwt,
      respectively) or QE (20mg/kg bwt) orally for 4 weeks. Group 5 rats received
      CdCl2, with 4 weeks recovery period. Results showed that cadmium accumulated in
      serum, testis and epididymis, decreased body weight, testicular and epididymal
      weights, sperm count, motility and viability. Cadmium decreased serum
      concentrations of reproductive hormones, but increased testicular glucose,
      lactate and lactate dehydrogenase activity. Cadmium decreased testicular
      enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non
      enzymatic (glutathione, vitamins C and E) antioxidants, and increased
      malondialdehyde and hydrogen peroxide. Cadmium down-regulated Bcl-2 protein, up
      regulated Bax protein, increased Bax/Bcl-2 ratio and cleaved caspase-3 activity.
      Histopathology of the testis showed decreased Johnsen's score and Leydig cell
      count. These negative effects were attenuated by QE administration, while
      withdrawal of CdCl2 did not appreciably reverse toxicity. We conclude that QE
      better protected the testis from CdCl2 toxicity than withdrawal of CdCl2
      administration.

PMID- 28756369
TI  - Antimicrobial activity of copaiba oil: A review and a call for further research.
AB  - Copaiba oil has been used for more than 390 years, however, considering the time
      of empirical use, there are a scarce number of publications on its activities.
      This essential oil is a phytomedicine proven to be efficient against some
      microorganisms. However, different from other phytomedicines which are well
      established, antimicrobial studies on copaiba oil can present some bias due to
      the lack of standardization. This review; summarizes recent works, from 2009 to
      2016, into the antibacterial and antifungal activities of copaiba oil; discusses
      issues affecting studies on this oil; and calls for more in vitro and clinical
      studies.

PMID- 28756370
TI  - Microbial communities in burial soil layers.

PMID- 28756371
TI  - IL-27 induces a pro-inflammatory response in human fetal membranes mediating
      preterm birth.
AB  - Inflammation at the maternal-fetal interface has been shown to be involved in the
      pathogenesis of preterm birth. Interleukin 27 (IL-27), a heterodimeric cytokine,
      is known to mediate an inflammatory response in some pregnancy complications. In
      this study, we aimed to determine whether IL-27 could induce an inflammatory
      reaction at the maternal-fetal interface that would mediate the onset of preterm
      birth. We found elevated expression of IL-27 in human peripheral serum and
      elevated expression of its specific receptor (wsx-1) on fetal membranes in cases
      of preterm birth. Moreover, the release of inflammatory markers (CXCL10, IFN
      gamma, MCP-1, IL-6, IL-1beta and TNF-alpha), especially CXCL10, was markedly
      augmented upon stimulation of IL-27 in the fetal membranes. Additionally, IL-27
      and IFN-gamma cooperated to amplify the expression of CXCL10 in the fetal
      membranes. Moreover, the production of CXCL10 was increased in IL-27-treated
      fetal membrane through JNK, PI3K or Erk signaling pathways. Finally, MMP2 and
      MMP9 were activated by IL-27 in human fetal membranes, which may be related to
      the onset of preterm premature rupture of membranes (pPROM). In conclusion, for
      the first time, we reported that the aberrant expression of IL-27 could mediate
      an excessive inflammatory response in fetal membranes through the JNK, PI3K or
      Erk signaling pathways, which contributes to preterm birth.

PMID- 28756372
TI  - Genetic diversity of Toxoplasma gondii isolates from ruminants: A systematic
      review.
AB  - Toxoplasma gondii is a protozoan capable of infecting all warm-blooded animals.
      This parasite has been classified into three major lineages. Our aim was to
      assess and compare the identified Types and genotypes in ruminants. From November
      2014 to April 2015, four English language databases and four Persian databases
      that reported data on the T. gondii genotyping in ruminants were searched.
      Overall, typing results of the 250/307 T. gondii isolates in all animals showed
      that Type II was a predominant Type (81.4%). In addition, genotyping data from
      the 82/215 T. gondii isolates or strains indicated that atypical genotypes were
      predominant (38.13%). This systematic review has demonstrated a large degree of
      genetic diversity in some countries. However, in the new nomenclature of
      genotyping, there are atypical or exotic genotypes, such as Chinese 1, Types Br
      (I, II, III and IV), and Type 12. Further genotyping studies are required to
      corroborate the current results.

PMID- 28756373
TI  - Genotyping of Lactobacillus sanfranciscensis isolates from Chinese traditional
      sourdoughs by multilocus sequence typing and multiplex RAPD-PCR.
AB  - Lactobacillus sanfranciscensis is the predominant lactic acid bacteria (LAB)
      species in Chinese traditional sourdoughs and conduces to the flavor and rheology
      properties of Chinese steamed bread, a staple food originated in China over
      1500years ago. The aim of this study is to describe the intraspecific diversity
      of 98 L. sanfranciscensis isolates from 11 Chinese traditional sourdoughs in
      different regions by multilocus sequence typing (MLST) and multiplex random
      amplified polymorphic DNA-polymerase chain reaction (multiplex RAPD-PCR). MLST
      scheme was reduced from six gene fragments (gdh, gyrA, mapA, nox, pgmA and pta)
      to five (gdh, gyrA, mapA, nox and pta) since the fragment of pgmA displayed only
      one allele. 10 different sequence types (STs) were revealed by MLST and 6 of them
      containing 79.8% of the isolates were classified into one clonal complex,
      demonstrating a close relationship among them. The multiplex-RAPD analysis was
      performed by employing the combined primers OPL-05+RD1 and divided the 98 L.
      sanfranciscensis isolates into 6 types with the similarity level of 70%.
      According to the result, it seems that the genotypic variations of L.
      sanfranciscensis strains showed by MLST have no relations to geographical origin.
      MLST seems to have a higher discriminatory power compared with multiplex-RAPD
      since it produced more groups, but multiplex-RAPD could help to distinguish some
      strains in the same ST. Hence, an optimal genotypic characterization of L.
      sanfranciscensis was obtained under the combination of MLST and multiplex-RAPD
      analysis, targeting different genetic variations.

PMID- 28756374
TI  - From sign to syndrome: Chilaiditi.

PMID- 28756375
TI  - Anterior, posterior and biomechanical parameters of cornea during pregnancy in
      healthy eyes: a cohort study.
AB  - BACKGROUND: To investigate the effect of pregnancy on anterior, posterior and
      biomechanical corneal parameters of healthy eyes. METHOD: In this prospective
      cohort study, 70 pregnant participants with clinically healthy eyes underwent
      corneal topographic imaging evaluation by Pentacam and biomechanical assessment
      by Ocular Response Analyzer (ORA) before pregnancy, at the third trimester of
      pregnancy (34th week of pregnancy) and 12 months after delivery. The same number
      of age-matched non-pregnant females was evaluated at the corresponding
      appointments as the control group. RESULTS: Assessment of the tomographic,
      topographic and ORA measurements before pregnancy, at the third trimester of
      pregnancy and 12 months post partum revealed no statistically significant changes
      in anterior and posterior corneal flat, steep and mean keratometry, anterior and
      posterior elevation measurements, central and thinnest corneal thickness, corneal
      hysteresis, corneal resistance factor and intraocular pressure measurements
      (p>0.05, repeated measures analysis of variance (ANOVA)). All of the study
      parameters returned to their baseline levels 1 year after delivery. The
      ophthalmic parameters of the non-pregnant group remained significantly unchanged
      during the study period (p>0.05, all comparisons, repeated measures ANOVA).
      Moreover, no statistically significant differences were found between pregnant
      and non-pregnant groups in the second (34th week of pregnancy) and third (post
      partum) appointments (p>0.05, all comparisons, one-way ANOVA). CONCLUSION: Our
      findings may suggest a physiological nature for ocular changes during pregnancy
      that these changes return to baseline values after delivery. The differences
      between tomographic, topographic and biomechanical corneal parameters before
      pregnancy, during pregnancy and post partum were not statistically or clinically
      significant.

PMID- 28756376
TI  - Obturator hernia: a rare cause of bowel obstruction.
AB  - An obturator hernia is a rare condition and an unusual cause of intestinal
      obstruction. With a challenging diagnosis, it has one of the highest mortality
      rates of all abdominal wall hernias. The authors present a case of an elderly
      woman with bowel obstruction secondary to an incarcerated obturator hernia. An 80
      year-old woman presented at the emergency room with complaints for the last 2
      days of nausea, vomiting, constipation and lower right abdominal pain that
      radiated down to the right medial thigh. Abdominal tenderness to deep palpation
      of the right iliac fossa and mildly distention were noted. A CT scan demonstrated
      bowel obstruction secondary to an incarcerated obturator hernia. The patient
      underwent emergency exploratory laparotomy. The incarcerated bowel was reduced
      and the defect was repaired with a plug of polypropylene mesh covered with
      peritoneum. The patient had an uneventful postoperative period and was discharged
      on the fifth postoperative day.

PMID- 28756377
TI  - Thrombolytic therapy for the treatment of acute ischaemic stroke in adults with
      homozygous sickle cell disease.
AB  - Stroke is a significant cause of morbidity and mortality in patients with
      homozygous sickle cell disease (SCD). A specific large-vessel vasculopathy is
      often responsible for both haemorrhagic and ischaemic strokes in patients with
      SCD. Although intravenous thrombolysis has been considered as a therapeutic
      option for acute ischaemic strokes in SCD, its use remains debated because of an
      increased risk of spontaneous intracranial haemorrhage reported in this disease.
      This risk of haemorrhage is mainly supported by the presence of a Moyamoya
      syndrome often associated with the specific vasculopathy in patients with
      homozygous SCD. We report two cases of patients with homozygous SCD treated with
      intravenous thrombolysis for an acute ischaemic stroke without haemorrhagic
      transformation. Our cases suggest that reperfusion strategy in acute ischaemic
      stroke in patients with homozygous SCD can be considered once associated Moyamoya
      syndrome has been ruled out. An international registry would be of interest as
      these situations are rare.

PMID- 28756378
TI  - Thalamic and cerebellar hypermetabolism and cortical hypometabolism during
      absence status epilepticus.
AB  - We report on a 17-year-old girl with absence status epilepticus who developed
      recurrent motionless confusional state and continuous generalised 3-4 Hz rhythmic
      delta waves on electroencephalogram (EEG). The patient had no history of absence,
      myoclonus or generalised convulsion. Her seizure was resistant to a combination
      of antiepileptic drugs including carbamazepine. Ictal positron emission
      tomography using [18F]fluorodeoxyglucose ([18F]FDG-PET) revealed hypermetabolism
      of the bilateral thalamus and cerebellum and hypometabolism of the frontal,
      parietal and posterior cingulate cortices. We diagnosed her seizure as absence
      status and obtained remission by changing medication. The findings of ictal
      metabolic alteration in previous studies and in our case confirm the pathogenic
      importance of the thalamus in absence status and that associated cortical
      deactivation and cerebellar activation may be related to the generation or
      maintenance of epileptic EEG discharges.

PMID- 28756379
TI  - Longitudinal Midline Sacral Split Fracture - A Rare Entity.
AB  - Fractures involving the central canal of the sacrum are rare injuries and can be
      transverse or longitudinal. Transverse fractures are by far common and associated
      with high incidence of neurological injuries. On the contrary, longitudinal
      midline split fracture is an extremely rare injury with minimal or no
      neurological injury. They are always associated with anterior pelvic ring
      fracture and are vertically stable needing only fixation of the anterior pelvic
      injury. Plating of the anterior pelvic ring in two planes would be beneficial
      than single plate to prevent gradual loss of reduction.

PMID- 28756380
TI  - A case of deep infection after instrumentation in dorsal spinal surgery: the
      management with antibiotics and negative wound pressure without removal of
      fixation.
AB  - Until today the role of spinal instrumentation in the presence of a wound
      infection has been widely discussed and recently many authors leave the hardware
      in place with appropriate antibiotic therapy. This is a case of a 65-year-old
      woman suffering from degenerative scoliosis and osteoporotic multiple vertebral
      collapses treated with posterior dorsolumbar stabilisation with screws and rods.
      Four months later, skin necrosis and infection appeared in the cranial wound with
      exposure of the rods. A surgical procedure of debridement of the infected tissue
      and package with a myocutaneous trapezius muscle flap was performed. One week
      after surgery, negative pressure wound therapy was started on the residual skin
      defect. The wound healed after 2 months. The aim of this case report is to focus
      on the utility of this method even in the case of hardware exposure and
      infection. This may help avoid removing instrumentation and creating instability.

PMID- 28756381
TI  - Acquired haemophilia A with a recalcitrant high-titre factor VIII inhibitor in
      the setting of interstitial lung disease.
AB  - Acquired haemophilia A (AHA) is a bleeding disorder that results from
      autoantibodies against factor VIII (FVIII). A 70-year-old man with a history of
      interstitial lung disease presented with spontaneous bleeding into his thigh. He
      had undetectable FVIII levels and a high-titre FVIII inhibitor (>2000Aca'!a?
      degrees Bethesda units/mL) and was diagnosed with AHA. He had several relapses,
      required multiple haemostatic and immunosuppressive treatments but eventually
      achieved a stable remission after 2Aca'!a? degrees years of therapy.Our patient
      matches the typical elderly male demographic of AHA. His relapsing course with
      remarkably high and persistent inhibitor titre highlights the need for close
      monitoring and aggressive upfront treatment. Whereas cyclophosphamide and
      steroids are often used first line in AHA, rituximab has also shown efficacy in
      refractory patients with high inhibitor levels. The FVIII and inhibitor
      concentration on presentation have been associated with treatment response and
      may be used as prognostic factors to tailor immunosuppressive regimens.

PMID- 28756382
TI  - Assessing the effects of changes in care commissioning guidelines at a tertiary
      centre in London on the provision of NHS-funded procedures of limited clinical
      effectiveness: an 11-year retrospective database analysis.
AB  - OBJECTIVES: The main objective of this study was to assess the impact of changes
      in care commissioning policies on National Health Service (NHS)-funded cosmetic
      procedures over an 11-year period at our centre. SETTING: The setting was a
      tertiary care hospital in London regulated by the North Central London Hospitals
      NHS Trust care commissioning group. PARTICIPANTS: We included all patients logged
      on to our database at the time of the study which was 2087 but later excluded 61
      from analysis due to insufficient information. PRIMARY AND SECONDARY OUTCOME
      MEASURES: The main outcome measures were the results of tribunal assessment for
      different cosmetic surgeries which were either accepted, rejected or inconclusive
      based on the panel meeting. RESULTS: There were a total of 2087 patient requests
      considered between 2004 and 2015, of which 715 (34%) were accepted, 1311 (63%)
      were declined and 61 (3%) had inconclusive results. The implementation of local
      care commissioning guidelines has reduced access to cosmetic surgeries. Within
      this period, the proportion of procedures accepted has fallen from 36% in 2004 to
      21% in 2015 (chi2; p<0.05, 95% CI). CONCLUSION: Local guidance on procedures of
      limited clinical effectiveness is a useful, although not evidence-based selection
      process to reduce access to cosmetic surgery in line with increasing financial
      constraints. However, patients with a physical impairment may not receive
      treatment in comparison to previous years, and this can have a negative impact on
      their quality of life.

PMID- 28756383
TI  - Relationship between initial therapy and blood pressure control for high-risk
      hypertension patients in the UK: a retrospective cohort study from the THIN
      general practice database.
AB  - OBJECTIVE: To examine the UK practice patterns in treating newly diagnosed
      hypertension and to determine whether subgroups of high-risk patients are more or
      less likely to follow particular therapeutic protocols and to reach blood
      pressure goals. DESIGN: Retrospective cohort study. SETTING: This study examined
      adults in The Health Improvement Network (THIN) UK general practice medical
      records database who were initiated on medication for hypertension. PARTICIPANTS:
      48 131 patients with essential hypertension diagnosed between 2008 and 2010 who
      were registered with a participating practice for a minimum of 13 months prior
      to, and 6 months following, initiation of therapy. We excluded patients with
      gestational hypertension or secondary hypertension. Patients were classified into
      risk groups based on blood pressure readings and comorbid conditions. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Odds of receiving single versus fixed or free-drug
      combination therapy and odds of achieving blood pressure control were assessed
      using multivariable logistic regression. RESULTS: The vast majority of patients
      (95.8%) were initiated on single drug therapy. Patients with high cardiovascular
      risk (patients with grade 2-3 hypertension or those with high normal/grade 1
      hypertension plus at least one cardiovascular condition pretreatment) had a
      statistically significant benefit of starting immediately on combination therapy
      when blood pressure control was the desired goal (OR: 1.23; 95% CI: 1.06 to 1.42)
      but, surprisingly, were less likely than patients with no risk factors to receive
      combination therapy (OR: 0.53; 95% CI: 0.47 to 0.59). CONCLUSIONS: Our results
      suggest that combination therapy may be indicated for patients with high
      cardiovascular risk, who accounted for 60.6% of our study population. The
      National Institute for Health and Care Excellence guideline CG34 of 2006 (in
      effect during the study period) recommended starting with single drug class
      therapy for most patients, and this advice does seem to have been followed even
      in cases where a more aggressive approach might have been considered.

PMID- 28756385
TI  - Impact of intrapatient variability (IPV) in tacrolimus trough levels on long-term
      renal transplant function: multicentre collaborative retrospective cohort study
      protocol.
AB  - INTRODUCTION: High intrapatient variability (IPV) in tacrolimus trough levels has
      been shown to be associated with higher rates of renal transplant failure. There
      is no consensus on what level of IPV constitutes a risk of graft loss. The
      establishment of such a threshold could help to guide clinicians in identifying
      at-risk patients to receive targeted interventions to improve IPV and thus
      outcomes. METHODS AND ANALYSIS: A multicentre Transplant Audit Collaborative has
      been established to conduct a retrospective study examining tacrolimus IPV and
      renal transplant outcomes. Patients in receipt of a renal transplant at
      participating centres between 2009 and 2014 and fulfilling the inclusion criteria
      will be included in the study. The aim is to recruit a minimum of 1600 patients
      with follow-up spanning at least 2 years in order to determine a threshold IPV
      above which a renal transplant recipient would be considered at increased risk of
      graft loss. The study also aims to determine any national or regional trends in
      IPV and any demographic associations. ETHICS AND DISSEMINATION: Consent will not
      be sought from patients whose data are used in this study as no additional
      procedures or information will be required from participants beyond that which
      would normally take place as part of clinical care. The study will be registered
      locally in each participating centre in line with local research and development
      protocols. It is anticipated that the results of this audit will be disseminated
      locally, in participating NHS Trusts, through national and international meetings
      and publications in peer-reviewed journals.

PMID- 28756384
TI  - Treatment and clinicopathological characteristics of lupus nephritis with anti
      neutrophil cytoplasmic antibody positivity: a case-control study.
AB  - OBJECTIVE: To assess the clinical features, pathological presentations,
      treatments and outcomes of lupus nephritis (LN) with anti-neutrophil cytoplasmic
      antibody (ANCA) positivity. DESIGN: A case-control study. METHODS: Patients
      (n=49) were retrospectively included from Jinling Hospital in China if presenting
      with biopsy-proven ANCA-positive LN between 1985 and 2008. Clinicopathological
      characteristics and outcomes were analysed and compared with those of a control
      group (n=1279). We further compared treatment responses and outcomes of ANCA
      positive LN patients based on the treatment issued. RESULTS: The study included
      40 women and 9 men (median age 33 years at biopsy): 38 with myeloperoxidase (MPO)
      ANCA, 7 with proteinase 3 (PR3)-ANCA and 4 with double positivity. ANCA-positive
      LN patients exhibited higher haematuria, serum creatinine levels and systemic
      lupus erythematosus disease activity index scores. On pathological evaluation,
      class IV LN was predominant, accounting for 61.22% of cases. Light microscopy
      revealed significantly higher activity index and chronicity index scores,
      including cellular crescents, interstitial inflammation, tubular atrophy and
      interstitial fibrosis. ANCA-positive LN patients receiving mycophenolate mofetil
      as induction therapy had a higher remission rate and better renal outcomes than
      those receiving cyclophosphamide. During follow-up, end-stage renal disease
      developed in seven (14.29%) ANCA-positive LN patients, all of them were MPO-ANCA
      positive. CONCLUSIONS: The characteristics of ANCA-positive LN were massive
      haematuria and advanced renal insufficiency. We observed a higher remission rate
      and better prognoses when using mycophenolate mofetil than when using
      cyclophosphamide as induction therapy.

PMID- 28756386
TI  - Study on factors inducing workplace violence in Chinese hospitals based on the
      broken window theory: a cross-sectional study.
AB  - OBJECTIVES: To explore the potential components of hospital workplace violence
      (HWPV) from the perspectives of hospital administrators and patients, and put
      forward corresponding strategies for its prevention and control. SETTING: Using
      convenience sampling methods, 116 hospitals in 14 provinces of China were
      surveyed using a self-designed questionnaire. METHODS: A cross-sectional study
      was used. PARTICIPANTS: Hospital administrators and patients from 116 hospitals
      in 14 provinces of China. RESULTS: First, hospital administrators point of
      workplace factors included six factors, with the following weighting
      coefficients: hospital administrator factors (29.40%), patient-related factors
      (20.08%), hospital environmental factors (19.45%), policy and institutional
      factors (11.92%), social psychological factors (10.26%), objective events factors
      (8.89%). Second, patients from the hospital workplace predisposing factors
      included three common factors. The weight coefficients of these were hospital
      related factors (60.27%), social and governmental factors (23.64%) and patient
      related factors (16.09%). CONCLUSIONS: A wide range of factors according to
      hospital administrators, patients and in the hospital environment play important
      roles in HWPV. From the perspectives of hospital administrators, communication
      skills and attitude to the service are important factors for inducing HWPV. From
      the perspective of patients, the characteristics of staff personalities and
      medical cognition are more important inducing factors. As far as social factors
      are concerned, economic compensation of medical malpractice is an important
      inducing factor for HWPV. In terms of environmental factors, management of
      Chinese medical hospitals, medical procedures and the layout of departments are
      all potential factors for the occurrence of violence. Corresponding defects were
      exposed in the health legal system and the supervision system for influencing
      public opinion.

PMID- 28756387
TI  - Enteric Salmonella in humans and food in the Middle East and North Africa:
      protocol of a systematic review.
AB  - INTRODUCTION: Non-typhoidal Salmonella is considered one of the leading causes of
      foodborne disease worldwide. This protocol provides methods that will be used to
      synthesise available epidemiological data on non-typhoidal enteric Salmonella in
      humans and food in Middle East and North Africa (MENA) region and to characterise
      the morbidity of human salmonellosis in this region. METHODS AND ANALYSIS: A
      systematic review will be conducted based on the Cochrane Collaboration handbook
      and will be reported following the items outlined in the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses guidelines. We will search PubMed,
      Embase, CAB Direct and Global Health Library (WHO) databases in order to identify
      relevant reports. Additionally, the literature search will be supplemented by
      checking references of the included reports and the identified reviews.
      Furthermore, we will hand-search conference proceedings and Ministry of Health's
      website of each country of the MENA region. We will use comprehensive search
      criteria with no time and no language restrictions. We will extract data on
      report and study characteristics, biological assay characteristics, individuals'
      demographic characteristics and on primary and secondary outcomes of interest. If
      appropriate, meta-analysis will be conducted in order to estimate pooled
      prevalence measures using DerSimonian and Laird random-effects models. We will
      conduct meta-regression analysis to explore the effect of study-level
      characteristics as potential sources of heterogeneity. ETHICS AND DISSEMINATION:
      The results of the systematic review will be disseminated in a peer-reviewed
      journal and presented at relevant conferences. TRIAL REGISTRATION NUMBER: The
      trial registration number is CRD42016046360.

PMID- 28756388
TI  - Drug-eluting stents in clinical routine: a 1-year follow-up analysis based on
      German health insurance administrative data from 2008 to 2014.
AB  - OBJECTIVES: To describe the use of drug-eluting stents (DESs) in the largest
      population of statutory health insurance members in Germany, including newly
      developed bio-resorbable vascular scaffolds (BVSs), and to evaluate 1-year
      complication rates of DES as compared with bare metal stents (BMSs) in this
      cohort. DESIGN: Routine data analysis of statutory health insurance claims data
      from the years 2008 to 2014. SETTING: The German healthcare insurance Allgemeine
      Ortskrankenkasse covers approximately 30% of the German population and is the
      largest nationwide provider of statutory healthcare insurance in Germany.
      PARTICIPANTS AND INTERVENTIONS: We included all patients with a claims record for
      a percutaneous coronary intervention (PCI) with either DES or BMS and
      additionally, from 2013, BVS. Patients with acute myocardial infarction (AMI)
      were excluded. MAIN OUTCOME MEASURE: major adverse cerebrovascular and
      cardiovascular event (MACCE, defined as mortality, AMI, stroke and transient
      ischaemic attack), bypass surgery, PCI and coronary angiography) at 1 year after
      the intervention. RESULTS: A total of 243 581 PCI cases were included (DES
      excluding BVS: 143 765; BVS: 1440; BMS: 98 376). The 1-year MACCE rate was 7.42%
      in the DES subgroup excluding BVS and 11.29% in the BMS subgroup. The adjusted OR
      for MACCE was 0.72 (95% CI 0.70 to 0.75) in patients with DES excluding BVS as
      compared with patients with BMS. In the BVS group, the proportion of 1-year MACCE
      was 5.0%. CONCLUSION: The analyses demonstrate a lower MACCE rate for PCI with
      DES. BVSs are used in clinical routine in selected cases and seem to provide a
      high degree of safety, but data are still sparse.

PMID- 28756390
TI  - A theoretical model for exercise progressions as part of a complex rehabilitation
      programme design.

PMID- 28756389
TI  - Sports injury and illness incidence in the Rio de Janeiro 2016 Olympic Summer
      Games: A prospective study of 11274 athletes from 207 countries.
AB  - OBJECTIVE: To describe the pattern of injuries and illnesses sustained during the
      Games of the XXXI Olympiad, hosted by Rio de Janeiro from 5 to 21 August 2016.
      METHODS: We recorded the daily incidence of athlete injuries and illnesses (1)
      through the reporting of all National Olympic Committee (NOC) medical teams and
      (2) in the polyclinic and medical venues by the Rio 2016 medical staff. RESULTS:
      In total, 11 274 athletes (5089 women, 45%; 6185 men, 55%) from 207 NOCs
      participated in the study. NOC and Rio 2016 medical staff reported 1101 injuries
      and 651 illnesses, equalling 9.8 injuries and 5.4 illnesses per 100 athletes over
      the 17-day period. Altogether, 8% of the athletes incurred at least one injury
      and 5% at least one illness. The injury incidence was highest in BMX cycling (38%
      of the athletes injured), boxing (30%), mountain bike cycling (24%), taekwondo
      (24%), water polo (19%) and rugby (19%), and lowest in canoe slalom, rowing,
      shooting, archery, swimming, golf and table tennis (0%-3%). Of the 1101 injuries
      recorded, 40% and 20% were estimated to lead to >=1 and >7 days of absence from
      sport, respectively. Women suffered 40% more illnesses than men. Illness was
      generally less common than injury, with the highest incidence recorded in diving
      (12%), open-water marathon (12%), sailing (12%), canoe slalom (11%), equestrian
      (11%) and synchronised swimming (10%). Illnesses were also less severe; 18% were
      expected to result in time loss. Of the illnesses, 47% affected the respiratory
      system and 21% the gastrointestinal system. The anticipated problem of infections
      in the Rio Olympic Games did not materialise, as the proportion of athletes with
      infectious diseases mirrored that of recent Olympic Games (3%). CONCLUSION:
      Overall, 8% of the athletes incurred at least one injury during the Olympic
      Games, and 5% an illness, which is slightly lower than in the Olympic Summer
      Games of 2008 and 2012.

PMID- 28756392
TI  - A comprehensive strength testing protocol offers no clinical value in predicting
      risk of hamstring injury: a prospective cohort study of 413 professional football
      players.
AB  - BACKGROUND: Hamstring injuries remain prevalent across a number of professional
      sports. In football, the incidence has even increased by 4% per year at the
      Champions League level over the last decade. The role of muscle strength or
      strength ratios and their association with risk of hamstring injury remain
      restricted by small sample sizes and inconclusive results. PURPOSE: The purpose
      of this study is to identify risk factors for hamstring injury in professional
      football players in an adequately powered, prospective cohort study. Using both
      established (isokinetic) and novel (eccentric hamstring test device) measures of
      muscle strength, we aimed to investigate the relationship between these strength
      characteristics over the entire range of motion with risk of hamstring injury.
      METHODS: All teams (n=18) eligible to compete in the premier football league in
      Qatar underwent a comprehensive strength assessment during their annual periodic
      health evaluation at Aspetar Orthopaedic and Sports Medicine Hospital in Doha,
      Qatar. Variables included isokinetic strength, Nordic hamstring exercise strength
      and dynamic hamstring: quadriceps ratios. RESULTS: Of the 413 players included
      (68.2% of all league players), 66 suffered a hamstring injury over the two
      seasons. Only isokinetic quadriceps concentric at 300 degrees /s (adjusted for
      bodyweight) was associated with risk of hamstring injury when considered
      categorically. Age, body mass and playing position were also associated with risk
      of hamstring injury. None of the other 23 strength variables examined were found
      to be associated with hamstring injury. CONCLUSION: The clinical value of
      isolated strength testing is limited, and its use in musculoskeletal screening to
      predict future hamstring injury is unfounded.

PMID- 28756393
TI  - Invited commentary: methodological issues in the design and analysis of
      randomised trials.

PMID- 28756394
TI  - Over half of the patients who undergo adjustable gastric banding may require
      revision bariatric surgery.

PMID- 28756395
TI  - The impact of bivalent HPV vaccine on cervical intraepithelial neoplasia by
      deprivation in Scotland: reducing the gap.
AB  - BACKGROUND: Cervical cancer disproportionately affects women from lower
      socioeconomic backgrounds. A human papillomavirus (HPV) vaccination programme was
      introduced in Scotland in 2008 with uptake being lower and inequitable in a catch
      up cohort run for the first three years of the programme compared with the
      routine programme. The socioeconomic differences in vaccine uptake have the
      potential to further increase the inequality gap in regards to cervical disease.
      METHODS: Vaccination status was linked to demographic, cytological and
      colposcopic data, which are routinely collected by the Scottish HPV surveillance
      system. Incidence rates and relative risk of cervical intraepithelial neoplasia
      (CIN) 1, 2 and 3 in unvaccinated and vaccinated women were stratified by birth
      year and deprivation status using Poisson regression. RESULTS: Women who received
      three doses of HPV vaccine have significantly decreased risk of CIN 1, 2 and 3.
      Vaccine effectiveness was greater in those women from the most deprived
      backgrounds against CIN 2 and 3 lesions. Compared with the most deprived,
      unvaccinated women, the relative risk of CIN 3 in fully vaccinated women in the
      same deprivation group was 0.29 (95% CI 0.2 to 0.43) compared with 0.62 (95% CI
      0.4 to 0.97) in vaccinated women in the least-deprived group. CONCLUSIONS: The
      HPV vaccine is associated with significant reductions in both low-grade and high
      grade CIN for all deprivation categories. However, the effect on high-grade
      disease was most profound in the most-deprived women. These data are welcoming
      and allay the concern that inequalities in cervical cancer may persist or
      increase following the introduction of the vaccine in Scotland.

PMID- 28756397
TI  - Penile transplantation as an appropriate response to botched traditional
      circumcisions in South Africa: an argument against.
AB  - Traditional male circumcision is a deeply entrenched cultural practice in South
      Africa. In recent times, there have been increasing numbers of botched
      circumcisions by untrained and unscrupulous practitioners, leading to genital
      mutilation and often, the need for penile amputation. Hailed as a world's first,
      a team of surgeons conducted the first successful penile transplant in Cape Town,
      South Africa in 2015. Despite the euphoria of this surgical victory, concerns
      about the use of this costly intervention in a context of severe resource
      constraints have been raised. In this paper, we explore some of the ethical
      implications of penile transplants as a clinical and public health response to
      the adverse consequences of traditional male circumcision. Given the current
      fiscal deficits in healthcare and public health sectors, how can one justify
      costly, high-technology interventions for conditions affecting a small section of
      the population? Since botched traditional male circumcisions are preventable, is
      a focus on penile transplantation as a form of treatment reasonable? Finally, do
      such interventions create undue expectations and false hope among a highly
      vulnerable and stigmatised group of young men? In this paper, we argue that given
      limited healthcare resources in South Africa and competing healthcare needs,
      prevention is a more appropriate response to botched traditional circumcisions
      than penile transplants.

PMID- 28756396
TI  - Reducing chemical exposures at home: opportunities for action.
AB  - Indoor environments can influence human environmental chemical exposures and,
      ultimately, public health. Furniture, electronics, personal care and cleaning
      products, floor coverings and other consumer products contain chemicals that can
      end up in the indoor air and settled dust. Consumer product chemicals such as
      phthalates, phenols, flame retardants and per- and polyfluorinated alkyl
      substances are widely detected in the US general population, including vulnerable
      populations, and are associated with adverse health effects such as reproductive
      and endocrine toxicity. We discuss the implications of our recent meta-analysis
      describing the patterns of chemical exposures and the ubiquity of multiple
      chemicals in indoor environments. To reduce the likelihood of exposures to these
      toxic chemicals, we then discuss approaches for exposure mitigation: targeting
      individual behaviour change, household maintenance and purchasing decisions,
      consumer advocacy and corporate responsibility in consumer markets, and
      regulatory action via state/federal policies. There is a need to further develop
      evidence-based strategies for chemical exposure reduction in each of these areas,
      given the multi-factorial nature of the problem. Further identifying those at
      greatest risk; understanding the individual, household and community factors that
      influence indoor chemical exposures; and developing options for mitigation may
      substantially improve individuals' exposures and health.

PMID- 28756398
TI  - Freedom of conscience in Europe? An analysis of three cases of midwives with
      conscientious objection to abortion.
AB  - While abortion has been legal in most developed countries for many years, the
      topic remains controversial. A major area of controversy concerns women's rights
      vis-a-vis the rights of health professionals to opt out of providing the service
      on conscience grounds. Although scholars from various disciplines have addressed
      this issue in the literature, there is a lack of empirical research on the topic.
      This paper provides a documentary analysis of three examples of conscientious
      objection on religious grounds to performing abortion-related care by midwives in
      different Member States of the European Union, two of which have resulted in
      legal action. These examples show that as well as the laws of the respective
      countries and the European Union, professional and church law each played a part
      in the decisions made. However, support from both professional and religious
      sources was inconsistent both within and between the examples. The authors
      conclude that there is a need for clear guidelines at both local and pan-European
      level for health professionals and recommend a European-wide forum to develop and
      test them.

PMID- 28756399
TI  - Lack of a pulmonary vein causing unilateral interlobular septal thickening.

PMID- 28756400
TI  - Perspectives of survivors, families and researchers on key outcomes for research
      in acute respiratory failure.
AB  - BACKGROUND: There is heterogeneity among the outcomes evaluated in studies of
      survivors of acute respiratory failure (ARF). AIM: To evaluate the importance of
      specific outcome domains to acute respiratory distress syndrome (ARDS) survivors,
      their family members and clinical researchers. METHODS: Nineteen outcome domains
      were identified from the National Institutes of Health's Patient Reported
      Outcomes Measurement Information System; WHO's International Classification of
      Functioning, Disability, and Health; Society of Critical Care Medicine's Post
      Intensive Care Syndrome (PICS); as well as patient, clinician and researcher
      input. We surveyed ARDS survivors, family members and critical care researchers,
      279 respondents in total, using a 5-point scale (strongly disagree, disagree,
      neutral, agree and strongly agree) to rate the importance of measuring each
      domain in studies of ARF survivors' postdischarge outcomes. MEASUREMENTS AND MAIN
      RESULTS: At least 80% of patients and family members supported (ie, rated 'agree'
      or 'strongly agree') that 15 of the 19 domains should be measured in all future
      studies. Among researchers, 6 of 19 domains were supported, with researchers less
      supportive for all domains, except survival (95% vs 72% support). Overall, four
      domains were supported by all groups: physical function, cognitive function,
      return to work or prior activities and mental health. CONCLUSION: Patient, family
      and researcher groups supported inclusion of outcome domains that fit within the
      PICS framework. Patients and family members also supported many additional
      domains, emphasising the importance of including patients/family, along with
      researchers, in consensus processes to select core outcome domains for future
      research studies.

PMID- 28756401
TI  - Double whammy: the disappearing right atrium.

PMID- 28756402
TI  - Comparison of a structured home-based rehabilitation programme with conventional
      supervised pulmonary rehabilitation: a randomised non-inferiority trial.
AB  - BACKGROUND: Standardised home-based pulmonary rehabilitation (PR) programmes
      offer an alternative model to centre-based supervised PR for which uptake is
      currently poor. We determined if a structured home-based unsupervised PR
      programme was non-inferior to supervised centre-based PR for participants with
      COPD. METHODS: A total of 287 participants with COPD who were referred to PR (187
      male, mean (SD) age 68 (8.86) years, FEV1% predicted 48.34 (17.92)) were
      recruited. They were randomised to either centre-based PR or a structured
      unsupervised home-based PR programme including a hospital visit with a healthcare
      professional trained in motivational interviewing, a self-management manual and
      two telephone calls. Fifty-eight (20%) withdrew from the centre-based group and
      51 (18%) from the home group. The primary outcome was dyspnoea domain in the
      chronic respiratory disease questionnaire (Chronic Respiratory Questionnaire Self
      Report; CRQ-SR) at 7 weeks. Measures were taken blinded. We undertook a modified
      intention-to-treat (mITT) complete case analysis, comparing groups according to
      original random allocation and with complete data at follow-up. The non
      inferiority margin was 0.5 units. RESULTS: There was evidence of significant
      gains in CRQ-dyspnoea at 7 weeks in both home and centre-based groups. There was
      inconclusive evidence that home-based PR was non-inferior to PR in dyspnoea (mean
      group difference, mITT: -0.24, 95% CI -0.61 to 0.12, p=0.18), favouring the
      centre group at 7 weeks. CONCLUSIONS: The standardised home-based programme
      provides benefits in dyspnoea. Further evidence is needed to definitively
      determine if the health benefits of the standardised home-based programme are non
      inferior or equivalent to supervised centre-based rehabilitation. TRIAL
      REGISTRATION NUMBER: ISRCTN81189044.

PMID- 28756403
TI  - Cochrane corner: beta-blockers for hypertension.

PMID- 28756404
TI  - Comment on 'Effects of injectable progestogen contraception versus the copper
      intrauterine device on HIV acquisition: sub-study of a pragmatic randomised
      controlled trial'.

PMID- 28756405
TI  - The recognition and management of sepsis and septic shock: a guide for non
      intensivists.
AB  - Sepsis is common, often fatal and requires rapid interventions to improve
      outcomes. While the optimal management of sepsis in the intensive care setting is
      the focus of extensive research interest, the mainstay of the recognition and
      initial management of sepsis will occur outside the intensive care setting.
      Therefore, it is key that institutions and clinicians remain well informed of the
      current updates in sepsis management and continue to use them to deliver
      appropriate and timely interventions to enhance patient survival. This review
      discusses the latest updates in sepsis care including the new consensus
      definition of sepsis, the outcome of the proCESS, ProMISe and ARISE trials of
      early goal directed therapy (EGDT), and the most recent guidelines from the
      Surviving Sepsis Campaign.

PMID- 28756406
TI  - Surgical shunts compared with endoscopic sclerotherapy for the treatment of
      variceal bleeding in adults with portal hypertension: a systematic review and
      meta-analysis.
AB  - AIM: Portal hypertension is a common complication of chronic liver disease and
      can cause variceal bleeding which is associated with high mortality. Choices for
      the treatment of variceal bleeding include surgical shunts and endoscopic
      sclerotherapy. The aim of this study was to compare the efficacy of surgical
      shunts and endoscopic sclerotherapy in treating variceal bleeding due to portal
      hypertension. DESIGN: Systematic review and meta-analysis. SETTING: Medline,
      PubMed, Cochrane and Google Scholar databases were searched until 12 February
      2015, for relevant randomised control trials. Twenty studies with a total of 1540
      participants were included. PATIENTS: Patients with variceal bleeding due to
      portal hypertension. INTERVENTIONS: Surgical shunts compared to endoscopic
      sclerotherapy. MAIN OUTCOME MEASURES: Rates of rebleeding, survival and
      hepatoencephalopathy, and length of hospital stay. RESULTS: Pooled data for 17
      studies showed that the rate of rebleeding was significantly more frequent with
      sclerotherapy compared with surgical shunt therapy (OR 3.99, 95% CI 2.98 to 5.33,
      p<0.001). The sclerotherapy patient group compared with the shunt group was less
      likely to develop hepatoencephalopathy (15 studies: pooled OR 0.53, 95% CI 0.31
      to 0.91, p=0.021) and had shorter hospital stays (pooled mean difference-4.32,
      95% CI- 7.97 to -0.66, p=0.021). No significant difference in the survival rate
      was observed between the two groups (seven studies: OR 1.01, 95% CI 0.63 to 1.62,
      p=0.964). CONCLUSION: This analysis indicated that the two types of treatment
      have similar mortality rates but differed with respect to rebleeding rate,
      incidence of hepatoencephalopathy and length of hospital stay.

PMID- 28756407
TI  - Resilience training: no more is needed or desired.

PMID- 28756408
TI  - Systematic review and meta-analysis: tools for the information age.
AB  - The amount of available biomedical information is vast and growing. Natural
      limitations of the way clinicians and researchers approach this treasure trove of
      information comprise difficulties locating the information, and once located,
      cognitive biases may lead to inappropriate use of the information. Systematic
      reviews and meta-analyses represent important tools in the information age to
      improve knowledge and action. Systematic reviews represent a census approach to
      identifying literature to avoid non-response bias. They are a necessary prelude
      to producing combined quantitative summaries of associations or treatment
      effects. Meta-analysis comprises the arithmetical techniques for producing
      combined summaries from individual study reports. Careful, thoughtful and
      rigorous use of these tools is likely to enhance knowledge and action. Use of
      standard guidelines, such as the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses guidelines, or embedding these activities within collaborative
      groups such as the Cochrane Collaboration, are likely to lead to more useful
      systematic review and meta-analysis reporting.

PMID- 28756409
TI  - Female and younger subjects have lower adherence in PrEP trials: a meta-analysis
      with implications for the uptake of PrEP service to prevent HIV.
AB  - OBJECTIVE: To estimate the medicine-taking compliance (MTC) level, explore its
      facilitators and barriers, and quantify the association between MTC level and pre
      exposure prophylaxis (PrEP) protective efficacy in individuals at risk of
      acquiring HIV being administered oral PrEP. DESIGN: Meta-analysis. DATA SOURCES:
      We searched PubMed, Cochrane and Embase databases for published randomized
      controlled trials (RCTs) pertaining to MTC of oral PrEP for HIV prevention up to
      16 January 2017. REVIEW METHODS: The pooled proportion of MTC and risk ratio (RR)
      of HIV incidences between intervention group and control group were estimated.
      RESULTS: We identified 10 eligible studies with 24 193 participants. The overall
      pooled MTC for oral HIV PrEP was 59.9% (95% CI 43.1% to 74.6%). Subgroup analyses
      revealed that the MTC level of participants aged <30 years was lower than those
      equal or older than 30 years (34.9% vs 69.6%, p<0.001); those studies that
      enrolled only women as participants had lower MTC than those only recruiting
      either only men or both men and women (31.3% vs 71.7% and 31.3% vs 71.0%, all
      p<0.01). Additionally, the HIV infection risk increased as the MTC level
      declines, with the incidence RRs being 0.28 (95% CI 0.19 to 0.41), 0.42 (95% CI
      0.29 to 0.62) and 0.75 (95% CI 0.45 to 1.25) in the good (>=80%), moderate
      (60%~80%) and poor (<60%) MTC subgroups, respectively (linear trend test p<0.01).
      CONCLUSION: According to the pooled proportion, the MTC of oral HIV PrEP is
      almost moderate, and its proportion in women and younger participants was
      relatively low. The protective efficacy of oral PrEP for HIV prevention increased
      with MTC level. These findings indicated that it is necessary to identify
      measures to enhance MTC of oral PrEP in future clinical usage, especially in
      women and younger participants with high HIV infection risk.

PMID- 28756410
TI  - Reduction of podocyte globotriaosylceramide content in adult male patients with
      Fabry disease with amenable GLA mutations following 6 months of migalastat
      treatment.
AB  - OBJECTIVE: Deficiency of alpha-galactosidase A (alphaGal-A) in Fabry disease
      leads to the accumulation mainly of globotriaosylceramide (GL3) in multiple renal
      cell types. Glomerular podocytes are relatively resistant to clearance of GL3
      inclusions by enzyme replacement therapy (ERT). Migalastat, an orally
      bioavailable small molecule capable of chaperoning misfolded alphaGal-A to
      lysosomes, is approved in the European Union for the long-term treatment of
      patients with Fabry disease and amenable GLA (alpha-galactosidase A enzyme)
      mutations. We aimed to examine if migalastat reduces GL3 content of podocytes in
      Fabry disease. METHODS AND ANALYSIS: We compared paired renal biopsies of eight
      adult men with amenable Fabry disease mutations at baseline and after 6 months of
      treatment with 150 mg migalastat every other day using quantitative unbiased
      electron microscopic morphometric methods. RESULTS: Migalastat treatment led to a
      reduction in mean total GL3 inclusion volume per podocyte in renal biopsies from
      baseline to 6 months. This reduction correlated precisely with reduced mean
      podocyte volume. There was also a direct relationship between reduction in
      podocyte foot process width and the reduction in mean total podocyte GL3 content
      following 6 months of migalastat treatment, suggestive of reduced podocyte
      injury. CONCLUSION: Migalastat treatment of 6 months duration in eight male
      patients with Fabry disease demonstrated effective GL3 clearance from the
      podocyte, an important and relatively ERT-resistant glomerular cell.

PMID- 28756412
TI  - Heartfelt images: learning cardiac science artistically.
AB  - There are limited curricular options for medical students to engage in art-making
      during their training. Yet, it is known that art-making confers a variety of
      benefits related to learning. This qualitative study utilises a visual
      methodology to explore students' art-making in the context of the cardiovascular
      sciences. The existence of a multiyear repository of medical/dental student
      generated, cardiac-inspired art, collected over 6 years, provided the opportunity
      to explore the nature of the art made. The aim was to categorise the art
      produced, as well as the depth and breadth of understanding required to produce
      the art. The data set included a wide variety of titled art (paintings,
      photographs, sketches, sculptures, collages, poetry and music/dance). Systematic
      curation of the collection, across all media, yielded three main categories:
      anatomical renderings, physiology/pathophysiology renderings and kinesthetic
      creations (music/dance/tactile). Overall (medical and dental) student-generated
      art suggested a high level of content/process understanding, as illustrated by
      attention to scientific detail, integration of form and function as well as the
      sophisticated use of visual metaphor and word play. Dental students
      preferentially expressed their understanding of anatomy and physiology
      kinesthetically, creating art that required manual dexterity as well as through
      choreography and dance. Combining art-making with basic science curricular
      learning invited the medical and dentistry students to link their understanding
      to different modes of expression and a non-biomedical way of knowing. Subsequent
      incorporation of the student-generated cardiac art into lectures exposed the
      entire class to creative pictorial expressions of anatomy, physiology and
      pathophysiology.

PMID- 28756411
TI  - Heterogeneous contribution of microdeletions in the development of common
      generalised and focal epilepsies.
AB  - BACKGROUND: Microdeletions are known to confer risk to epilepsy, particularly at
      genomic rearrangement 'hotspot' loci. However, microdeletion burden not
      overlapping these regions or within different epilepsy subtypes has not been
      ascertained. OBJECTIVE: To decipher the role of microdeletions outside hotspots
      loci and risk assessment by epilepsy subtype. METHODS: We assessed the burden,
      frequency and genomic content of rare, large microdeletions found in a previously
      published cohort of 1366 patients with genetic generalised epilepsy (GGE) in
      addition to two sets of additional unpublished genome-wide microdeletions found
      in 281 patients with rolandic epilepsy (RE) and 807 patients with adult focal
      epilepsy (AFE), totalling 2454 cases. Microdeletions were assessed in a combined
      and subtype-specific approaches against 6746 controls. RESULTS: When hotspots are
      considered, we detected an enrichment of microdeletions in the combined epilepsy
      analysis (adjusted p=1.06*10-6,OR 1.89, 95% CI 1.51 to 2.35). Epilepsy subtype
      specific analyses showed that hotspot microdeletions in the GGE subgroup
      contribute most of the overall signal (adjusted p=9.79*10-12, OR 7.45, 95% CI
      4.20-13.5). Outside hotspots , microdeletions were enriched in the GGE cohort for
      neurodevelopmental genes (adjusted p=9.13*10-3,OR 2.85, 95% CI 1.62-4.94). No
      additional signal was observed for RE and AFE. Still, gene-content analysis
      identified known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate
      genes across epilepsy subtypes that were not deleted in controls. CONCLUSIONS:
      Our results show a heterogeneous effect of recurrent and non-recurrent
      microdeletions as part of the genetic architecture of GGE and a minor
      contribution in the aetiology of RE and AFE.

PMID- 28756413
TI  - Migration and work in postwar Australia: mortality profile comparisons between
      Australian and Italian workers exposed to blue asbestos at Wittenoom.
AB  - OBJECTIVES: Three hundred and thirty thousand Italians arrived in Australia
      between 1945 and 1966, many on assisted passage schemes where the worker agreed
      to a 2-year unskilled employment contract. Italians were the largest of 52
      migrant groups employed at the Wittenoom blue asbestos mining and milling
      operation. We compare mortality from asbestos-related diseases among Italian and
      Australian workers employed at Wittenoom. METHODS: A cohort of 6500 male workers
      was established from employment records and followed up at state and national
      mortality and cancer registries. SMRs were calculated to compare mortality with
      the Western Australian male population. Time-varying Cox proportional hazards
      models compared the risk of mesothelioma between Australian and Italian workers.
      RESULTS: 1031 Italians and 3465 Australians worked at Wittenoom between 1943 and
      1966. Duration of employment was longer for the Italian workers, although the
      concentration of exposure was similar. The mesothelioma mortality rate per 100
      000 was higher in Italians (184, 95% CI 148 to 229) than Australians (128, 95% CI
      111 to 149). The risk of mesothelioma was greater than twofold (HR 2.27, 95% CI
      1.43 to 3.60) in Italians at the lowest asbestos exposure category (<10 fibre
      years/per mL). CONCLUSIONS: A hierarchy in migration, isolation and a shortage of
      workers led to Italians at Wittenoom incurring higher cumulative exposure to blue
      asbestos and subsequently a greater rate of malignant mesothelioma than
      Australian workers. IMPACT: Poor working conditions and disparities between
      native and foreign-born workers has had a detrimental and differential impact on
      the long-term health of the workforce.

PMID- 28756414
TI  - Work-related risk factors for specific shoulder disorders: a systematic review
      and meta-analysis.
AB  - The objective of this systematic review and meta-analysis is to examine which
      work-related risk factors are associated with specific soft tissue shoulder
      disorders. We searched the electronic databases of Medline and Embase for
      articles published between 2009 and 24 March 2016 and included the references of
      a systematic review performed for the period before 2009. Primary cross-sectional
      and longitudinal studies were included when outcome data were described in terms
      of clinically assessed soft tissue shoulder disorders and at least two levels of
      work-related exposure were mentioned (exposed vs less or non-exposed). Two
      authors independently selected studies, extracted data and assessed study
      quality. For longitudinal studies, we performed meta-analyses and used GRADE
      (Grades of Recommendations, Assessment, Development and Evaluation) to assess the
      evidence for the associations between risk factors and the onset of shoulder
      disorders. Twenty-seven studies met the inclusion criteria. In total, 16 300
      patients with specific soft tissue shoulder disorders from a population of 2 413
      722 workers from Denmark, Finland, France, Germany and Poland were included in
      the meta-analysis of one case-control and six prospective cohort studies. This
      meta-analysis revealed moderate evidence for associations between shoulder
      disorders and arm-hand elevation (OR=1.9, 95% CI 1.47 to 2.47) and shoulder load
      (OR=2.0, 95% CI 1.90 to 2.10) and low to very low evidence for hand force
      exertion (OR=1.5, 95% CI 1.25 to 1.87), hand-arm vibration (OR=1.3, 95% CI 1.01
      to 1.77), psychosocial job demands (OR=1.1, 95% CI 1.01 to 1.25) and working
      together with temporary workers (OR=2.2, 95% CI 1.2 to 4.2). Low-quality evidence
      for no associations was found for arm repetition, social support, decision
      latitude, job control and job security. Moderate evidence was found that arm-hand
      elevation and shoulder load double the risk of specific shoulder disorders. Low
      to very-low-quality evidence was found for an association between hand force
      exertion, hand-arm vibration, psychosocial job demands and working together with
      temporary workers and the incidence of specific shoulder disorders.

PMID- 28756415
TI  - Cognitive-behavioural therapy and return-to-work intervention for patients on
      sick leave due to common mental disorders: a randomised controlled trial.
AB  - OBJECTIVES: Common mental disorders (CMDs) cause great individual suffering and
      long-term sick leave. Cognitive-behavioural therapy (CBT) effectively treats
      CMDs, but sick leave is not reduced to the same extent as psychiatric symptoms.
      Research results regarding return-to-work interventions (RTW-Is) and their effect
      on sick leave are inconclusive. The aim of this study was to evaluate CBT, a RTW
      I and combined CBT and RTW-I (COMBO) for primary care patients on sick leave due
      to CMDs. METHODS: Patients with CMDs (n=211) were randomised to CBT (n=64), RTW-I
      (n=67) or COMBO (n=80). Sick-leave registry data after 1 year and blinded
      Clinician's Severity Rating (CSR) of symptoms post-treatment and at follow-ups
      after 6 and 12 months were primary outcomes. RESULTS: There was no significant
      difference between treatments in days on sick leave 1 year after treatment start
      (mean difference in sick-leave days range=9-27). CBT led to larger reduction of
      symptoms post-treatment (CSR; Cohen's d=0.4 (95% CI 0.1 to 0.8)) than RTW-I,
      whereas COMBO did not differ from CBT or RTW-I. At follow-up, after 1 year, there
      was no difference between groups. All treatments were associated with large pre
      treatment to post-treatment improvements, and results were maintained at 1-year
      follow-up. CONCLUSION: No treatment was superior to the other regarding reducing
      sick leave. All treatments effectively reduced symptoms, CBT in a faster pace
      than RTW-I, but at 1-year follow-up, all groups had similar symptom levels.
      Further research is needed regarding how CBT and RTW-I can be combined more
      efficiently to produce a larger effect on sick leave while maintaining effective
      symptom reduction.

PMID- 28756416
TI  - The economic burden of lung cancer and mesothelioma due to occupational and para
      occupational asbestos exposure.
AB  - OBJECTIVES: To estimate the economic burden of lung cancer and mesothelioma due
      to occupational and para-occupational asbestos exposure in Canada. METHODS: We
      estimate the lifetime cost of newly diagnosed lung cancer and mesothelioma cases
      associated with occupational and para-occupational asbestos exposure for calendar
      year 2011 based on the societal perspective. The key cost components considered
      are healthcare costs, productivity and output costs, and quality of life costs.
      RESULTS: There were 427 cases of newly diagnosed mesothelioma cases and 1904 lung
      cancer cases attributable to asbestos exposure in 2011 for a total of 2331 cases.
      Our estimate of the economic burden is $C831 million in direct and indirect costs
      for newly identified cases of mesothelioma and lung cancer and $C1.5 billion in
      quality of life costs based on a value of $C100 000 per quality-adjusted life
      year. This amounts to $C356 429 and $C652 369 per case, respectively.
      CONCLUSIONS: The economic burden of lung cancer and mesothelioma associated with
      occupational and para-occupational asbestos exposure is substantial. The estimate
      identified is for 2331 newly diagnosed, occupational and para-occupational
      exposure cases in 2011, so it is only a portion of the burden of existing cases
      in that year. Our findings provide important information for policy decision
      makers for priority setting, in particular the merits of banning the mining of
      asbestos and use of products containing asbestos in countries where they are
      still allowed and also the merits of asbestos removal in older buildings with
      asbestos insulation.

PMID- 28756417
TI  - The combined effects of job demand and control, effort-reward imbalance and work
      family conflicts on the risk of major depressive episode: a 4-year longitudinal
      study.
AB  - PURPOSE: Work-related psychosocial factors may precipitate the onset of
      depression. In occupational mental health research, there are three widely used
      theoretical models, namely, job demand and control (JD-C), effort-reward
      imbalance (ERI) and work-family conflicts (WFC). However, the interaction between
      these models and their combined effect on the risk of major depression in the
      workplace is largely unknown. The aim of this study is to examine the
      longitudinal combined effects of JD-C, ERI and WFC on the risk of major
      depression in the working population. METHODS: Longitudinal data (2008-2013) were
      collected on randomly selected participants (n=4200) from the working population
      of the province of Alberta, Canada, at baseline and 1-, 2-, 3- and 4-year follow
      up. Data about JD-C, ERI, WFC and major depression were collected by trained
      interviewers using a computer-assisted telephone interviewing method. Generalised
      estimating equations for longitudinal modelling were used. RESULTS: There was an
      independent association between high ERI and high WFC at tx and major depression
      at tx+1 (OR 1.56, 95% CI 1.25 to 1.96; OR 1.33, 95% CI 1.16 to 1.52),
      respectively. The combined effects of JD-C and ERI, ERI and WFC, and WFC and JD-C
      on the risk of major depression were as follows: OR 1.71, 95% CI 1.22 to 2.42, OR
      2.47, 95% CI 1.99 to 3.49 and OR 2.21, 95% CI 1.48 to 3.30, respectively. The
      relative excess risks attributable to the interactions were statistically non
      significant. CONCLUSIONS: Work-related psychosocial factors are associated with
      increased risk of major depression over time, but their combined effect is not
      synergistic. The effects of the factors depicted in the three occupational health
      models on the risk of major depression appear to be additive.

PMID- 28756418
TI  - One-Year Clinical Outcomes of Patients Presenting With ST-Segment Elevation
      Myocardial Infarction Caused by Bifurcation Culprit Lesions Treated With the
      Stentys Self-Apposing Coronary Stent: Results From the APPOSITION III Study.
AB  - OBJECTIVE: To investigate outcomes in patients with ST-segment elevation
      myocardial infarction (STEMI) after treatment with the Stentys self-apposing
      stent (Stentys SAS; Stentys S.A.) for bifurcation culprit lesions. BACKGROUND:
      The nitinol, self-expanding Stentys was initially developed as a dedicated
      bifurcation stent. The stent facilitates a provisional strategy by accommodating
      its diameter to both the proximal and distal reference diameters and offering an
      opportunity to "disconnect" the interconnectors, opening the stent toward the
      side branch. METHODS: The APPOSITION (a post-market registry to assess the
      Stentys self-expanding coronary stent in acute myocardial infarction) III study
      was a prospective, multicenter, international, observational study including
      STEMI patients undergoing primary percutaneous coronary intervention (PCI) with
      the Stentys SAS. Clinical endpoints were evaluated and stratified by bifurcation
      vs non-bifurcation culprit lesions. RESULTS: From 965 patients included, a total
      of 123 (13%) were documented as having a bifurcation lesion. Target-vessel
      revascularization (TVR) rates were higher in the bifurcation subgroup (16.4% vs
      10.0%; P=.04). Although not statistically significant, other endpoints were
      numerically higher in the bifurcation subgroup: major adverse cardiac events
      (MACE; 12.7% vs 8.8%), myocardial infarction (MI; 3.4% vs 1.8%), and
      definite/probable stent thrombosis (ST; 5.8% vs 3.1%). However, when postdilation
      was performed, clinical endpoints were similar between bifurcation and non
      bifurcation lesions: MACE (8.7% vs 8.4%), MI (1.2% vs 0.7%), and
      definite/probable ST (3.7% vs 2.4%). CONCLUSIONS: The use of the Stentys SAS was
      safe and feasible for the treatment of bifurcation lesions in the setting of
      primary PCI for STEMI treatment with acceptable 1-year cardiovascular event
      rates, which improved when postdilation was performed.

PMID- 28756419
TI  - Contrast Minimization With the New-Generation DyeVert Plus System for Contrast
      Reduction and Real-Time Monitoring During Coronary and Peripheral Procedures:
      First Experience.
AB  - BACKGROUND: Several strategies have been envisioned to reduce the risk of
      contrast-induced nephropathy, but the most modifiable approach for a treating
      physician is to minimize contrast administration. To date, there is no report on
      the use of Osprey Medical's new-generation DyeVert Plus system in coronary or
      peripheral applications. We aimed to appraise the role of the DyeVert Plus system
      inclusive of contrast reduction and real-time monitoring in a consecutive series
      of patients undergoing coronary or peripheral invasive procedures. METHODS:
      Baseline, procedural, and outcome details for patients undergoing coronary or
      peripheral invasive procedures were collected from our institutional database. We
      primarily focused on total and relative amount of contrast saved, as calculated
      and displayed by the DyeVert Plus system. RESULTS: The DyeVert Plus system was
      used in 10 patients. All procedures were successfully completed with adequate and
      high-quality angioscopic and angiographic images. No adverse events occurred up
      to discharge in any patients, with the notable exception of 1 case of
      asymptomatic and uneventful contrast-induced nephropathy. Average contrast volume
      was 79.9 +/- 48.8 mL (95% confidence interval [CI], 53.2 to 109.4), thanks to an
      absolute saving of 55.8 +/- 31.9 mL (95% CI, 39.1 to 76.7; P<.05) and a relative
      saving of 41.8 +/- 7.3% (95% CI, 37.5 to 46.4; P<.05). Comparison of contrast
      volume estimates between DyeVert Plus vs manual measurements showed a minimal
      difference of 1.6 +/- 1.9 mL (95% CI, 2.9 to 0.5; P<.05). CONCLUSION: Use of the
      new-generation DyeVert Plus system inclusive of contrast reduction and real-time
      monitoring is feasible in both coronary and peripheral applications while
      significantly reducing contrast volume.

PMID- 28756420
TI  - Safety and Feasibility of Rotational Atherectomy in Elderly Patients With Severe
      Aortic Stenosis.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) followed by transcatheter
      aortic valve replacement (TAVR) is an alternative to surgery in patients with
      severe aortic stenosis (AS) and coronary artery disease (CAD). In many, the
      coronary arteries are severely calcified and best treated with rotational
      atherectomy (RA). However, RA is not routinely performed in severe AS patients
      due to safety concerns. There is a paucity of data on the safety of RA in severe
      AS patients with calcific CAD. METHODS: We retrospectively analyzed the medical
      records of 29 patients with severe AS who underwent elective RA-facilitated PCI
      at our center between January 1, 2011 and December 31, 2015. RESULTS: Twenty-nine
      patients (mean age, 79.8 +/- 8.8 years) were enrolled. Mean aortic valve area was
      0.71 +/- 0.20 cm2, mean aortic valve gradient was 40.32 +/- 9.88 mm Hg. All PCIs
      were successful (mean diameter stenosis, 86.3 +/- 7.6%; mean burr size, 1.62 +/-
      0.19 mm). Nineteen patients (65.5%) required temporary pacemaker. Eight patients
      (27.6%) required vasopressors during PCI. There was a significant reduction in
      systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial
      pressure (MAP), and heart rate (HR) during RA, but without clinical events. No
      procedure was aborted and there were no deaths or clinical myocardial
      infarctions. CONCLUSION: RA-facilitated PCI can be safely performed in elderly
      patients with severe AS and severely calcified CAD with low risk of
      complications. There was a significant but transient drop in SBP, DBP, MAP, and
      HR during RA. However, this was not associated with clinically significant
      adverse events.

PMID- 28756421
TI  - Arterial Cutaneous Femoral Fistulous Tract Closure Using Surgiflo Hemostatic
      Matrix: A Novel Adjunct for Post-TAVR Access-Site Management.
AB  - Several options are available to address hemostasis at the end of a cardiac
      catheterization or percutaneous transfemoral transcatheter aortic valve
      replacement (TAVR) when conventional options are ineffective. To date, there have
      been few studies exploring the use of a topical thrombin preparation, as one of
      its main contraindications is that it cannot be used intravascularly due to risk
      of embolization. The following case shows safe utilization of Surgiflo hemostatic
      gel matrix under fluoroscopic guidance against an inflated balloon in order to
      achieve closure of a fistulous tract from a femoral artery access site during
      percutaneous TAVR.

PMID- 28756422
TI  - Transradial Coronary Angiogram in a Sitting Position.
AB  - Transradial coronary angiography has significantly increased in the United States
      over the last decade. When the patient is unable to lie down despite analgesia
      and conscious sedation, general anesthesia may be recommended. We report the
      feasibility of transradial coronary angiogram in a sitting position.

PMID- 28756423
TI  - Incidental Detection of Arteria Lusoria During Transradial Coronary Intervention.
AB  - Transradial access has become popular and preferred approach in coronary
      interventions due to high success rate, low risk of complications and patients'
      comfort. However various anatomical variations and anomalies may pose technical
      challenge. Arteria lusoria is an uncommon condition which is technically
      challenging and may warrant cross-over to alternate access. We report a middle
      aged male presenting with acute coronary syndrome in which arteria lusoria was
      incidentally detected during right transradial coronary intervention.

PMID- 28756424
TI  - Cavotricuspid-Isthmus Dependent Flutter or Left-Sided Atrial Tachycardia?
AB  - A 52-year-old man with previous mitral valve replacement, cavotricuspid isthmus,
      and left-sided roof-line ablation for previous typical atrial flutter and
      tachycardia presented with recurrence of symptoms with an atrial tachycardia
      measuring 260 ms cycle length on electrocardiogram. Rhythmia electroanatomical
      mapping (Boston Scientific) was performed to understand the mechanism of
      arrhythmia and to guide ablative treatment.

PMID- 28756425
TI  - Inappropriate ICD Shock From Perceived Ventricular Fibrillation During Balloon
      Manipulation at the Time of Percutaneous Coronary Intervention.
AB  - The authors demonstrate that device manipulation during percutaneous coronary
      intervention can result in "noise," which can be perceived as an arrhythmia
      resulting in an inappropriate shock. Although rare, this possibility should be
      considered when an operator encounters a difficult to traverse lesion in a
      patient with an ICD.

PMID- 28756426
TI  - Handle With Care: A Ductus Arteriosus Aneurysm in an Elderly Patient.
AB  - A ductus arteriosus aneurysm (DAA) was corrected with an 18 mm Amplatzer patent
      foramen ovale occluder. DAA is a rare finding, with sporadic cases reported (the
      vast majority in children and infants). In the elderly, it poses serious
      therapeutic challenges, as the risk of rupture is counterbalanced by the high
      risk of its correction, which requires surgery or placement of an endovascular
      prosthesis in a critical region such as the aortic arch.

PMID- 28756427
TI  - Thrombolysis: A Useful Tool in the Primary PCI Cupboard.
AB  - A 44-year-old woman presented to the emergency department with central crushing
      chest pain and dynamic anterior ST elevation on a background of a known left
      bundle-branch block on her electrocardiogram. Past medical history included
      insulin-dependent diabetes, asthma, fibromyalgia, and a gradually failing kidney
      transplant. This case demonstrates the rarely utilized niche role for
      intracoronary thrombolysis in STEMI treatment in the modern angioplasty era.

PMID- 28756428
TI  - Changes in stature from the Upper Paleolithic to the Medieval period in Western
      Europe.

PMID- 28756429
TI  - Interacting with Genomic Data: Clinician Requirements and Prototype Structure.
AB  - Healthcare is currently being transformed by the introduction of genomic
      sequencing - a major advancement in personalised medicine. This advent provides
      new opportunities for clinicians to use genomic data in decision making about
      patient diagnosis and treatment, but this can only be achieved through access to
      data and support in its use. Engaging with clinicians in the development of
      decision support tools will optimise relevance and adoption of genomic sequencing
      in healthcare. In this study, existing data from clinician workshops and
      interviews together with horizon scanning of relevant technologies were used to
      define clinician portal specifications. We describe a preliminary structure of a
      decision support tool for use by clinicians and the manner in which the
      technology may be evaluated.

PMID- 28756430
TI  - The Development of a National Census of the Health Information Workforce: Expert
      Panel Recommendations.
AB  - BACKGROUND: There is a need to develop a national census of the health
      information workforce to inform the planning and forecasting of the workforce and
      inform education and training needs. Yet, this raises a number of issues that
      need to be incorporated into the planning stage. This paper discusses the issues
      and recommendations for the development of a national health information
      workforce census and an Expert Panel's recommendations for how we should proceed.
      METHODS: Nominated participants from Australia and New Zealand participated as
      Expert Panel members in focus groups to identify and discuss the issues.
      Recommendations were identified during the focus groups and documented for
      participant verification. These were then grouped into themes. RESULTS AND
      DISCUSSION: The themes of the issues and considerations identified in the focus
      groups were: Aim of the census; Census advertisement; Census delivery;
      Participants; Longitudinal study; Types of data elements; Data development and
      standards; Data ownership, access and governance; Global census; Dissemination of
      results.

PMID- 28756431
TI  - Downtime in Digital Hospitals: An Analysis of Patterns and Causes Over 33 Months.
AB  - The use of health information technology (IT) is increasing around the world.
      However, as complex IT systems are implemented, new types of errors are
      introduced. These can disrupt workflow and care delivery, and even lead to
      patient harm. The purpose of this paper is to examine the patterns and causes of
      IT system downtime in a hospital setting. We examined all the downtime events
      that were recorded by a hospital IT department from February 2010 to October
      2012. On average downtime disrupted care delivery for 49 hours per year with 51%
      of total downtime between 9 am and 5 pm. These results show that there is a need
      for safer design and implementation of IT systems. Further studies are required
      to measure the effects of downtime on care delivery and patient outcomes in
      digital hospitals.

PMID- 28756432
TI  - Talking to Toddlers: Drawing on Mothers' Perceptions of Using Wearable and Mobile
      Technology in the Home.
AB  - BACKGROUND: Mother-child interactions often give rise to opportunities for early
      language learning in the context of everyday life. Persuasive technology has the
      potential to influence maternal language behaviours in the home and promote
      mothers' active engagement in the development of their children's communication
      skills. AIM: This paper explored maternal perceptions regarding the use of a
      language tracking wearable (Language Environment Analysis; LENA) device and a
      parent education smartphone application in an 8-week trial with their young
      children. METHODS: Mother/child dyads were enrolled in a feasibility trial
      designed to obtain objective auditory and linguistic data from each child's
      naturalistic settings (Control Condition), provide feedback to mothers about
      their child's home language environment (LENA Feedback Condition), and to explore
      effectiveness of an app designed to promote meaningful parent/child interactions
      during daily routines (LENA Feedback and App Condition). RESULTS AND DISCUSSION:
      The majority of mothers (80%) who participated in the trial reported a preference
      for using the mobile app and/or LENA technology again. Maternal responses during
      this pilot informed the design of an ongoing, prospective language intervention
      study for parents and their young children with significant hearing loss.

PMID- 28756433
TI  - Point-of-Care Testing Across Rural and Remote Emergency Departments in Australia:
      Staff Perceptions of Operational Impact.
AB  - New South Wales (NSW) Health Pathology is implementing one of the world's largest
      managed PoCT services across rural and remote Emergency Departments (EDs) in New
      South Wales, Australia to improve patient access to care. The aim of this
      qualitative study was to gain a context-rich understanding of the operational
      impact of the NSW rollout of PoCT across rural and remote ED settings as
      experienced by frontline clinical staff. Clinical professionals (n=14)
      participated in interviews and focus groups in August 2015 at four rural and
      remote NSW EDs. Participants perceived that PoCT provided greater access to
      pathology thus facilitating more efficient and effective patient care via faster
      test turnaround and time to treatment and more effective decisions about the need
      to transfer patients to appropriate sites when required. These factors have a
      potentially important role in saving lives. Staff also identified innovative and
      disruptive challenges to clinical work patterns associated with PoCT
      implementation, particularly in relation to work flows, resource allocation and
      the governance arrangements.

PMID- 28756434
TI  - Simulating Human Carer with an Avatar to Improve Medication Adherence.
AB  - Non-adherence to medication and treatment regimens is considered as a major issue
      in the healthcare industry as it can lead to negative consequences. Various
      strategies have been applied to improve adherence, however many of these
      strategies lack the interaction and personalisation-aspect which has been shown
      to be crucial to the patients. This paper discusses the importance of
      personalised interaction in improving patients' medication adherence, and the
      characteristics needed in an avatar to simulate such human-human interactions.

PMID- 28756435
TI  - User Perceptions of the Implementation of an Electronic Medication Management
      System in a Paediatric Setting.
AB  - The roll-out of a hospital-wide electronic medication management system (eMMS) is
      a challenging task, requiring planning, coordination, communication and change
      management. This research aimed to explore the views of doctors and nurses about
      the strategy used to implement an eMM system in a paediatric hospital. Semi
      structured interviews were performed during the first week of the implementation
      on each ward, and were then followed up three and six weeks post implementation.
      In total, 90 users (60 nurses and 30 doctors) were asked about their impressions
      of the implementation, as well as their perceptions of training and IT support.
      Qualitative thematic analysis was performed by three researchers. Most users
      perceived the implementation of the eMM to be positive overall. Although
      perceptions of the implementation process remained largely consistent across the
      six weeks, users identified several areas where improvements were needed,
      especially early in implementation, including resources, planning, roll-out
      strategy and training. These findings are useful for future implementations of
      eMM systems in paediatric hospitals.

PMID- 28756436
TI  - A Systematic Literature Review on Evaluation of Digital Tools for Authoring
      Evidence-Based Clinical Guidelines.
AB  - To facilitate the clinical guideline (GL) development process, different groups
      of researchers have proposed tools that enable computer-supported tools for
      authoring and publishing GLs. In a previous study we interviewed GL authors in
      different Norwegian institutions and identified tool shortcomings. In this follow
      up study our goal is to explore to what extent GL authoring tools have been
      evaluated by researchers, guideline organisations, or GL authors. This article
      presents results from a systematic literature review of evaluation (including
      usability) of GL authoring tools. A controlled database search and backward snow
      balling were used to identify relevant articles. From the 12692 abstracts found,
      188 papers were fully reviewed and 26 papers were identified as relevant. The
      GRADEPro tool has attracted some evaluation, however popular tools and platforms
      such as DECIDE, Doctor Evidence, JBI-SUMARI, G-I-N library have not been subject
      to specific evaluation from an authoring perspective. Therefore, we found that
      little attention was paid to the evaluation of the tools in general. We could not
      find any evaluation relevant to how tools integrate and support the complex GL
      development workflow. The results of this paper are highly relevant to GL
      authors, tool developers and GL publishing organisations in order to improve and
      control the GL development and maintenance process.

PMID- 28756437
TI  - SnoMAP: Pioneering the Path for Clinical Coding to Improve Patient Care.
AB  - The increasing demand for healthcare and the static resources available
      necessitate data driven improvements in healthcare at large scale. The SnoMAP
      tool was rapidly developed to provide an automated solution that transforms and
      maps clinician-entered data to provide data which is fit for both administrative
      and clinical purposes. Accuracy of data mapping was maintained.

PMID- 28756438
TI  - Feedback and Training to Improve Use of an Electronic Prescribing System: A
      Randomised Controlled Trial.
AB  - Excessive presentation of alerts in electronic prescribing systems (ePS) results
      in 'alert fatigue' which reduces alert effectiveness and frustrates users.
      Previous research at our study site showed high rates of duplication alerts, some
      of which were the result of doctors not using available short-cut functions in
      the ePS. This study aimed to improve uptake of short-cut functions and so reduce
      alert fatigue by trialing two interventions: feedback and training. Fifty doctors
      were randomised to one of three groups: Control, Feedback or Training. The
      Feedback group received an individualised feedback report via email and the
      Training group received brief face-to-face refresher training. Participants
      partook in informal interviews to discuss the training and the ePS in use. The
      proportion of orders which triggered a duplication alert was our primary outcome
      measure. Neither intervention had a significant impact on duplication alert rate
      (Feedback: 80.8% vs. 77.8% of orders, Training: 77.5% vs. 76.5% of orders; all
      p>0.05). We identified a number of factors related to the intervention, ePS and
      prescribing environment that contributed to this result. Rather than focusing on
      changing prescribing behaviour, we suggest a more effective and appropriate
      approach is to redesign the ePS so that fewer and more meaningful alerts are
      presented.

PMID- 28756439
TI  - What Factors Determine the Use of an Electronic Test Result Acknowledgement
      System? - A Qualitative Study Across Two EDs.
AB  - Electronic medical record-based test results management interventions hold the
      potential to reduce errors in the test result follow-up process. However,
      ensuring the adaptability of such systems to the clinical environment has proven
      challenging. The aim of this study was to explore how contextual factors can
      influence senior emergency physicians' experience and perceived impacts of an
      electronic result acknowledgement system across two Emergency Departments. Semi
      structured, in-depth interviews relating to physician test result acknowledgement
      processes before and after system implementation were conducted with 14 senior
      Emergency Physicians across two Australian metropolitan teaching hospitals.
      Perceived impacts of the electronic test result acknowledgement system on test
      result endorsement varied in terms of: changes to workflow, impacts on patient
      safety; and changes to documentation practices. Existing work practices and the
      departmental staffing mix and roles play a part in determining the nature of
      change that an electronic result acknowledgement system is likely to produce.

PMID- 28756440
TI  - Understanding Health Professionals' Informal Learning in Online Social Networks:
      A Cross-Sectional Survey.
AB  - Online social networks (OSNs) enable health professionals to learn informally,
      for example by sharing medical knowledge, or discussing practice management
      challenges and clinical issues. Understanding how learning occurs in OSNs is
      necessary to better support this type of learning. Through a cross-sectional
      survey, this study found that learning interaction in OSNs is low in general,
      with a small number of active users. Some health professionals actively used OSNs
      to support their practice, including sharing practical and experiential
      knowledge, benchmarking themselves, and to keep up-to-date on policy, advanced
      information and news in the field. These health professionals had an overall
      positive learning experience in OSNs.

PMID- 28756441
TI  - A Semantic-Based K-Anonymity Scheme for Health Record Linkage.
AB  - Record linkage is a technique for integrating data from sources or providers
      where direct access to the data is not possible due to security and privacy
      considerations. This is a very common scenario for medical data, as patient
      privacy is a significant concern. To avoid privacy leakage, researchers have
      adopted k-anonymity to protect raw data from re-identification however they
      cannot avoid associated information loss, e.g. due to generalisation. Given that
      individual-level data is often not disclosed in the linkage cases, but yet
      remains potentially re-discoverable, we propose semantic-based linkage k
      anonymity to de-identify record linkage with fewer generalisations and eliminate
      inference disclosure through semantic reasoning.

PMID- 28756442
TI  - Preparing E-Health Ready Graduates: A Qualitative Focus Group Study.
AB  - BACKGROUND: Well documented demand for an e-health ready workforce is placing
      increasing pressure on universities to deliver essential e-health education. AIM:
      We aimed to explore stakeholders' perceptions of e-health knowledge and skills
      anticipated of workforce-ready tertiary graduates from clinical health degree
      programs. METHOD: A qualitative research study of a purposively selected sample
      of 23 key informants with expertise and/or experience in e-health education,
      practice and/or policy was conducted. Data collection involved focus group
      interviews that were recorded, transcribed verbatim and underwent thematic
      analysis. FINDINGS: Three primary themes about e-health education and preparation
      of health graduates emerged from the analyses: 1) Reinforce fundamental
      competencies, 2) Acknowledge and adapt existing competencies, and 3) Introduce
      and provide opportunities for new learning. CONCLUSIONS AND IMPLICATIONS: This
      study will inform the articulation of a consensus driven set of core competencies
      for a cross-faculty e-health curriculum that aligns with workforce expectations.
      There is also potential for vertical integration of findings into workforce
      development programs.

PMID- 28756443
TI  - Enhancing General Practitioners Participation in a Virtual Community of Practice
      for Continuing Medical Education: An Exploratory Study.
AB  - As sources of medical information grow online, Virtual Communities of Practice
      (VCoPs) have evolved into a potential tool that allows General Practitioners
      (GPs) to interact through the sharing of their experience and knowledge. However,
      literature reports that GPs are reluctant to participate in VCoPs especially for
      their continuing medical education (CME). Currently, no study has explored the
      design and structural aspects of VCoPs that may lead to enhancing GPs'
      participation in such online communities. Hence, this paper explores how GPs
      envisage the use of a VCoP for their CME and how to enhance their participation
      by conducting an exploratory qualitative study of two focus groups with 10 GPs in
      each group, accompanied by a specialist and a nurse. Our empirical findings
      identified two key contributions: i) seven themes that need to be incorporated in
      the VCoP to enable and support GP's CME through the use of a VCoP; ii) three
      recommendations to take into consideration for researchers when evaluating VCoPs
      for CME.

PMID- 28756444
TI  - Engaging Consumers with Musculoskeletal Conditions in Health Research: A User
      Centred Perspective.
AB  - Consumers are frequently involved in different kinds of health research, such as
      clinical trials, focus groups, and surveys. As pointed out by different studies,
      recruiting and involving consumers to participate in academic research can be
      challenging. While different research and guidelines are provided to instruct
      researchers to recruit participants ethically, they seldom consider the needs and
      expectations of consumers. In this research, we interviewed 23 consumers with
      musculoskeletal conditions in Australia, to understand their needs and
      motivations for participating in research from a user-centred perspective. Based
      on these data, we systematically summarise consumers' feedback into four main
      themes: (1) Research as Learning Opportunity; (2) The Important Role of
      Communities and Health Professionals; (3) Research Transparency and Updates; and
      (4) Special Needs for People with MSK Conditions. As a result, a few
      recommendations are proposed and researchers should further consider these when
      designing consumer-based studies. Ultimately, with a better understanding of
      consumers, we hope that our research can enhance consumer engagement and improve
      their participation in health research.

PMID- 28756445
TI  - Socialising Health Burden Through Different Network Topologies: A Simulation
      Study.
AB  - An aging population and the expectation of premium quality health services
      combined with the increasing economic burden of the healthcare system requires a
      paradigm shift toward patient oriented healthcare. The guardian angel theory
      described by Szolovits [1] explores the notion of enlisting patients as primary
      providers of information and motivation to patients with similar clinical history
      through social connections. In this study, an agent based model was developed to
      simulate to explore how individuals are affected through their levels of
      intrinsic positivity. Ring, point-to-point (paired buddy), and random networks
      were modelled, with individuals able to send messages to each other given their
      levels of variables positivity and motivation. Of the 3 modelled networks it is
      apparent that the ring network provides the most equal, collective improvement in
      positivity and motivation for all users. Further study into other network
      topologies should be undertaken in the future.

PMID- 28756447
TI  - A Spatial Dashboard for Alzheimer's Disease in New South Wales.
AB  - This paper illustrates a proof of concept scenario for the application of
      comprehensive data visualisation methods in the rapidly changing aged care
      sector. The scenario we explored is population ageing and the dementias with an
      emphasis on the spatial effects of change over time at the Statistical Area 2
      (SA2) level for the state of New South Wales. We did this using a combination of
      methods, culminating in the use of the Tableau software environment to explore
      the intersections of demography, epidemiology and their formal cost of care
      implications. In addition, we briefly illustrate how key infrastructure data can
      be included in the same data management context by showing how service providers
      can be integrated and mapped in conjunction with other analyses. This is an
      innovative and practical approach to some of the complex issues already faced in
      the health and aged care sectors which can only become more pronounced as
      population ageing progresses.

PMID- 28756446
TI  - E-Health Readiness for Teams: A Comprehensive Conceptual Model.
AB  - The use of information technology in the delivery of healthcare services is
      pervasive but faces many barriers. We propose a four-factor comprehensive
      conceptual model to provide a measure of interdisciplinary healthcare readiness
      to provide healthcare services using e-health. We incorporate factors from a
      series of focus group studies and the wider literature and construct a conceptual
      model. We utilise the Delphi method to establish content validity and use a
      series of Q sorts for initial construct validity. This model will improve patient
      outcomes through healthcare teams identifying barriers to using e-health
      effectively and efficiently.

PMID- 28756448
TI  - Improved Prediction of Procedure Duration for Elective Surgery.
AB  - Accurate surgery duration estimation is essential for efficient use of hospital
      operating theatres and the scheduling of elective patients. This study focuses on
      analysing the performance of previously developed surgery duration prediction
      algorithms at a specialty level to gain further insight on their performance. We
      also evaluate algorithm performance after applying filtering to exclude
      unreliable data from modelling, and develop and validate new ensemble approaches
      for prediction. These are shown to significantly improve the prediction accuracy
      of the algorithms. Employing filtered data delivers a reduction in overall
      prediction error of 44% (Mean Absolute Percentage Error from 0.68 to 0.38)
      employing the Random Forests algorithm, while using the newly developed ensemble
      approach delivers a Mean Absolute Percentage Error of 0.31, a reduction of 55%
      when compared to the original error, and a reduction of 18% when compared to the
      Random Forests performance on filtered data.

PMID- 28756449
TI  - Unplanned Returns to Hospital Care: A Linked Data Study.
AB  - The linkage of data across facilities and settings of care provides a holistic
      view of the patient journey through the healthcare system. This study, through
      data linkage, reviews alternative approaches to the measurement of unplanned
      returns to care in NSW public hospital emergency departments and admitted patient
      care settings. The study shows that existing measures of unplanned returns do not
      identify the true extent of these events and highlight the need to develop new
      approaches to measurement using the increasing availability of integrated patient
      information.

PMID- 28756450
TI  - Consumer Perspectives on MyHealth Record: A Review.
AB  - The vision for Australia's national electronic health record system included
      empowering consumers to become active participants in their own health care. This
      paper aims to critically review the literature on consumer perspectives of
      Australia's My Health Record (formerly PCEHR). The review is based on a subset of
      articles (n=12) identified in the Australian EHR Repository (N=143), a repository
      of metadata of Australian Research on EHR located at Flinders University. Results
      show low levels of awareness and concerns about sharing records and equity of
      access for all Australians, which in view of the change from opt in to opt out
      raises concerns about explicit consent. Improved promotion and support, along
      with different models of access might lead to higher consumer engagement with,
      and use, of My Health Record, especially for populations at risk of digital
      exclusion.

PMID- 28756451
TI  - Weekly Hospital Workforce Data: A Data Visualisation Exercise.
AB  - Quantifying the health workforce in terms of overall staff numbers and their
      ratio to patients under their care can strengthen analytical studies designed to
      inform policy regarding how hospital services are delivered. Information about
      staffing is traditionally obtained via location-specific audits or self-reported
      information gleaned from surveys which hold potential biases around time
      dependence and recall. In contrast, work presented in this paper describes the
      derivation of useful workforce metrics from routine hospital financial and
      clinical information systems that overcome these biases. Staffing data is
      aggregated, visualised and linked to patient demand to gain insight into spatial
      and temporal variations in hospital staffing and workload. Overall, hospital
      staff resourcing varies noticeably across a week, with staff numbers and staff-to
      patient ratios dropping to low levels at night and across a weekend. Exploration
      of staff-to-staff ratios allows further insight into staff dynamics across a week
      and the variation of supervision level.

PMID- 28756452
TI  - Enabler for Interdisciplinary eHealthcare: A Qualitative Study.
AB  - The complex relations between Health Technologies and clinical practices have
      been the focus of intensive research in recent years. This research represents a
      shift towards a holistic view where evaluation of health technologies is linked
      to organisational practices. In this paper, we address the gaps in existing
      literature regarding the holistic evaluation of e-health in clinical practice. We
      report the results from a qualitative study conducted to gain insight into e
      health in practice within an interdisciplinary healthcare domain. Findings from
      this qualitative study, provides the foundation for the creation of a generic
      measurement model that allows for the comparative analysis of health technologies
      and assist in the decision-making of its stakeholders.

PMID- 28756455
TI  - Effectiveness of Aerobic Exercise as an Augmentation Therapy for Inpatients with
      Major Depressive Disorder: A Preliminary Randomized Controlled Trial.
AB  - : e or female patients, 18-80 years, diagnosed with a Major Depressive Episode,
      were randomly assigned to three weeks of augmentation therapy with aerobic (n=6)
      or stretching exercise (n=6). Depression was rated, at several time points using
      the 21-item Hamilton Depression Scale (HAM-D), Beck Depression Inventory (BDI)
      and other scales. RESULTS: According to the HAM-D, there were four (out of six)
      responders in the aerobic group, two of whom achieved remission, and none in the
      stretching group. According to the BDI, there were two responders in the aerobic
      group who were also remitters and none in the stretching group. CONCLUSIONS: The
      results of this small study suggest that aerobic exercise significantly improves
      treatment outcome when added to antidepressant medication. However, due to the
      small sample size the results must be regarded as preliminary and further studies
      are needed to confirm the findings.

PMID- 28756456
TI  - Clinical Predictors of Surgical Outcomes and Imaging Features in Single Segmental
      Cervical Spondylotic Myelopathy with Lower Cervical Instability.
AB  - BACKGROUND Cervical degenerative changes are the most common cause of cervical
      spondylotic myelopathy (CSM) and lower cervical instability (LCI). The purpose of
      this study was to investigate the associated factors of MRI signal changes and
      prognosis in single segmental CSM accompanied by LCI. MATERIAL AND METHODS A
      total of 122 patients met the inclusion criteria and were enrolled in this study
      with a minimum follow-up period of 2 years. According to the absence/presence of
      LCI, patients were divided into the unstable group (n=43 [35.2%]) and the stable
      group (n=79 [64.8%]). Clinical data and radiological parameters were compared
      between groups. RESULTS The occurrence rate of increased signal intensity (ISI)
      of the spinal cord was 72.1% in the unstable group and 44.3% in the stable group,
      and the difference was significant. There were significant differences in
      preoperative JOA score, duration of symptoms, and number of physical signs
      between the 2 groups (p<0.001, =0.001 and <0.001, respectively). The recovery
      rate of the JOA score in the unstable group was significantly lower than in the
      stable group (p<0.001). Long duration of symptoms, low preoperative JOA score,
      and more preoperative physical signs were significantly correlated with low JOA
      recovery rate. CONCLUSIONS Patients suffering from CSM with LCI have higher
      incidence of ISI of the spinal cord. Longer duration of symptoms, lower
      preoperative JOA score, and more preoperative physical signs were highly
      predictive of poor surgical outcomes for patients with single segmental CSM with
      LCI.

PMID- 28756457
TI  - A comparison of electronic and manual fracture risk assessment tools in screening
      elderly male US veterans at risk for osteoporosis.
AB  - : This study compares four screening tools in their ability to predict
      osteoporosis. We found that there was no significant difference between the
      tools. These results provide support for the use of automated screening tools
      which work in conjunction with the electronic medical record and help improve
      screening rates for osteoporosis. INTRODUCTION: The purpose of this study is to
      compare the performance of four fracture risk assessment tools (FRATs) in
      identifying osteoporosis by bone mineral density (BMD) T-score: Veterans Affairs
      Fracture Absolute Risk Assessment Tool (VA-FARA), World Health Organization's
      Fracture Risk Assessment Tool (FRAX), electronic FRAX (e-FRAX), and Osteoporosis
      Self-Assessment Screening Tool (OST). METHODS: We performed a cross-sectional
      analysis of all patients enrolled in the VA Salt Lake City bone health team (BHT)
      who had completed a DXA scan between February 1, 2012, and February 1, 2013. DXA
      scan results were obtained by chart abstraction. For calculation of FRAX,
      osteoporosis risk factors were obtained from a screening questionnaire completed
      prior to DXA. For VA-FARA and e-FRAX, risk factors were derived from the
      electronic medical record (EMR). Clinical risk scores were calculated and
      compared against the gold standard of DXA-based osteoporosis. Sensitivity,
      specificity, and predictive values were calculated. Receiver operator
      characteristic (ROC) curves were plotted, and areas under the curve (AUC) were
      compared. RESULTS: A cohort of 463 patients met eligibility criteria (mean age
      80.4 years). One hundred twelve patients (24%) had osteoporosis as defined by DXA
      T-score <=-2.5. Sensitivity, specificity, and predictive values were calculated.
      ROC statistics were compared and did not reach statistical significance
      difference between FRATs in identifying DXA-based osteoporosis. CONCLUSIONS: Our
      study suggests that all FRATs tested perform similarly in identifying
      osteoporosis among elderly, primarily Caucasian, male veterans. If these
      electronic screening methods perform similarly for fracture outcomes, they could
      replace manual FRAX and thus improve efficiency in identifying individuals who
      should be sent for DXA scan.

PMID- 28756458
TI  - Comparison of intermediate- and low-frequency shock wave lithotripsy for
      pediatric kidney stones.
AB  - The aim of the study to compare low and intermediate shock wave frequency rates
      in terms of success and complications for treating pediatric kidney stones. This
      retrospective study was performed on 58 consecutive pediatric patients (24 girls,
      34 boys) who underwent shock wave lithotripsy (SWL) for kidney stones with an
      electrohydraulic lithotripter between April 2014 and March 2016. In the first
      year, all children underwent SWL with a frequency of 90 SWs/min as an
      intermediate frequency (Group 90), and in the second year all children were
      treated by SWL using 60 SWs/min as a low frequency (Group 60). The mean age of
      the patients was 5.87 +/- 4.5 years. There were no significant differences in
      age, gender, stone characteristics and SWL energy level between the groups. Stone
      free status was achieved in 14, 6 and 4 children in group 60; and in 10, 6 and 4
      children in group 90 after one, two and three sessions, respectively. The stone
      free rates were 80 and 74.1% after SWL and 90 and 88.9% after additional
      treatment in groups 60 and 90, respectively. The total median shock pulses were
      2000 and 3600 in groups 60 and 90, respectively (p = 0.115). Efficiency quotients
      were 51.93 and 44.47 in groups 60 and 90, respectively. The mean total anesthesia
      times and complication rates did not differ between the groups. The low and
      intermediate frequency of SWL provided similar stone clearance in pediatric renal
      stones with similar anesthesia times. However, low SWL tended to need fewer shock
      pulses (2000/3600) for stone clearance, but the trend was not significant.

PMID- 28756459
TI  - Comparison of STONE, CROES and Guy's nephrolithometry scoring systems for
      predicting stone-free status and complication rates after percutaneous
      nephrolithotomy in obese patients.
AB  - In this study, we aim to evaluate the accuracy of STONE (stone size, tract
      length, obstruction, number of involved calyces, and essence/stone density),
      Clinical Research Office of the Endourological Society (CROES), and Guy's
      nephrolithometry scoring systems (NSS) in obese patients. The charts of patients
      who underwent percutaneous nephrolithotomy (PNL) between June 2008 and June 2016
      were retrospectively analyzed. Calculations of the STONE, CROES, and Guy's NSS
      were performed by a resident who was well informed regarding each NSS. Patients
      were classified under nine scores according to STONE, four grades according to
      CROES, and four grades according to Guy's NSS. In total, 248 obese patients were
      enrolled in the study. Stone size was significantly higher in patients without
      stone-free status (p = 0.001). In patients who were stone-free and those with
      residual stones, the mean STONE score was 9.71 and 9.23 (p = 0.160), CROES was
      172 and 129 (p = 0.001), and Guy's NSS was 1.67 and 2.75 (p = 0.001).
      Multivariate regression analysis identified the CROES and Guy's NSS were
      independent factors for PNL success in obese patients (p = 0.01 and p = 0.01,
      respectively). The CROES and Guy's NSS showed good accuracy with PNL success (AUC
      = 0.777 and AUC = 0.844, respectively). None of the three NSS systems were
      statically associated with a complication rate (p = 0.23 for STONE, p = 0.14 for
      CROES, and p = 0.51 for Guy's NSS). Our study demonstrated that CROES and Guy's
      NSS were independent predictors of stone-free rate following PNL in obese
      patients. Our study also revealed that three of the NSSs were not useful for
      predicting PNL complications in obese patients.

PMID- 28756460
TI  - Ursolic acid activates the TGR5 receptor to enhance GLP-1 secretion in type 1
      like diabetic rats.
AB  - Endogenous Takeda G-protein-coupled receptor 5 (TGR5), G-protein-coupled bile
      acid receptor 1 (GPBAR1), regulates glucose metabolism. In animals, TGR5
      activation by a chemical agonist may increase incretin secretion and reduce the
      blood sugar level. Recently, betulinic acid has been suggested to activate TGR5.
      Ursolic acid is a well-known pentacyclic triterpenoid that is similar to
      betulinic acid. It is of special interest to determine the potential effect of
      ursolic acid on TGR5. Therefore, we transfected cultured Chinese hamster ovary
      (CHO-K1) cells with the TGR5 gene. The functions of the transfected cells were
      confirmed via glucose uptake using a fluorescent indicator. Moreover, NCI-H716
      cells that secreted incretin were also investigated, and the glucagon-like
      peptide (GLP-1) levels were quantified using ELISA kits. In addition,
      streptozotocin (STZ)-induced type 1-like diabetic rats were used to identify the
      effect of ursolic acid in vivo. Ursolic acid concentration dependently increased
      glucose uptake in CHO-K1 cells expressing TGR5. In NCI-H716 cells, ursolic acid
      induced a concentration-dependent elevation in GLP-1 secretion, which was
      inhibited by triamterene at the effective concentrations to block TGR5. Ursolic
      acid also increased the plasma GLP-1 level via TGR5 activation, which was further
      characterized in vivo with type 1-like diabetic rats. Moreover, ursolic acid is
      more effective than betulinic acid in reduction of hyperglycemia and increase of
      GLP-1 secretion. Therefore, we demonstrated that ursolic acid can activate TGR5,
      enhancing GLP-1 secretion in vitro and in vivo. Therefore, ursolic acid is
      suitable for use in TGR5 activation.

PMID- 28756463
TI  - A Comparative Evaluation of Different Sediment Quality Guidelines for Metal and
      Metalloid Pollution in the Xiangjiang River, Hunan, China.
AB  - To evaluate intensively the quality of the sediments contaminated by heavy metals
      and metalloids in the Xiangjiang River, 52 surface sediment samples were
      collected at 13 sites and different combinations of empirical and theoretical
      sediment quality indexes, the consensus-based sediment quality guidelines,
      sediment toxicity degree, and equilibrium partitioning method were applied. The
      average contents of Cd, Pb, Cu, Zn, Hg, Cr, and As in the sampled surface
      sediments were significantly higher than the background values of trace elements
      in soils of Hunan Province, China. Moreover, speciation fraction analyses
      revealed that Cd, Hg, and Pb in the sediments were dominated by the more
      bioavailable organic or exchangeable fractions, whereas the major species of As
      and Cr were the less bioavailable residual fractions after strong acid treatment.
      In addition, all indexes showed that these metals posed a median-high degree of
      toxic risk to benthic organisms in sediments from nearly all of the sampling
      sites along the Xiangjiang River. Cd, followed by Cu and Pb, erected the most
      severe ecological risk. Pearson correlation and linear regression analyses
      between the mean PEC quotients, sediment toxicity degree, interstitial water
      criteria toxic units, and sediment pollution index showed that these indexes were
      relatively consistent to assess the quality of sediments contaminated by heavy
      metals and metalloids in the Xiangjiang River. Our results will facilitate the
      proposal of proper sediment quality guidelines for the Xiangjiang River.

PMID- 28756461
TI  - Adolescent stress leads to glutamatergic disturbance through dopaminergic
      abnormalities in the prefrontal cortex of genetically vulnerable mice.
AB  - BACKGROUND: Stress during the adolescent period influences postnatal maturation
      and behavioral patterns in adulthood. Adolescent stress-induced molecular and
      functional changes in neurons are the key clinical features of psychiatric
      disorders including schizophrenia. OBJECTIVE: In the present study, we exposed
      genetically vulnerable mice to isolation stress to examine the molecular changes
      in the glutamatergic system involving N-methyl-d-aspartate (NMDA) receptors via
      dopaminergic disturbance in the prefrontal cortex (PFc). RESULTS: We report that
      late adolescent stress in combination with Disrupted-in-Schizophrenia 1 (DISC1)
      genetic risk elicited alterations in glutamatergic neurons in the PFc, such as
      increased expression of glutamate transporters, decreased extracellular levels of
      glutamate, decreased concentration of d-serine, and impaired activation of NMDA
      Ca2+/calmodulin kinase II signaling. These changes resulted in behavioral
      deficits in locomotor activity, forced swim, social interaction, and novelty
      preference tests. The glutamatergic alterations in the PFc were prevented if the
      animals were treated with an atypical antipsychotic drug clozapine and a dopamine
      D1 agonist SKF81297, which suggests that the activation of dopaminergic neurons
      is involved in the regulation of the glutamatergic system. CONCLUSION: Our
      results suggest that adolescent stress combined with dopaminergic abnormalities
      in the PFc of genetically vulnerable mice induces glutamatergic disturbances,
      which leads to behavioral deficits in the young adult stage.

PMID- 28756462
TI  - Effects of GABA-B receptor positive modulator on ketamine-induced psychosis
      relevant behaviors and hippocampal electrical activity in freely moving rats.
AB  - RATIONALE: Decreased GABAB receptor function is proposed to mediate some symptoms
      of schizophrenia. OBJECTIVES: In this study, we tested the effect of CGP7930, a
      GABAB receptor positive allosteric modulator, on ketamine-induced psychosis
      relevant behaviors and hippocampal electrical activity in behaving rats. METHODS:
      Electrodes were bilaterally implanted into the hippocampus, and cannulae were
      placed into the lateral ventricles of Long-Evans rats. CGP7930 or vehicle was
      injected intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.), alone or
      15 min prior to ketamine (3 mg/kg, subcutaneous) injection. Paired click auditory
      evoked potentials in the hippocampus (AEP), prepulse inhibition (PPI), and
      locomotor activity were recorded before and after drug injection. RESULTS:
      CGP7930 at doses of 1 mg/kg (i.p.) prevented ketamine-induced deficit of PPI.
      CGP7930 (1 mg/kg i.p.) also prevented the decrease in gating of hippocampal AEP
      and the increase in hippocampal gamma (65-100 Hz) waves induced by ketamine.
      Unilateral i.c.v. infusion of CGP7930 (0.3 mM/1 MUL) also prevented the decrease
      in gating of hippocampal AEP induced by ketamine. Ketamine-induced behavioral
      hyperlocomotion was suppressed by 5 mg/kg i.p. CGP7930. CGP7930 alone, without
      ketamine, did not significantly affect integrated PPI, locomotion, gating of
      hippocampal AEP, or gamma waves. CGP7930 (1 mg/kg i.p.) increased
      heterosynaptically mediated paired pulse depression in the hippocampus, a measure
      of GABAB receptor function in vivo. CONCLUSIONS: CGP7930 reduces the behavioral
      and electrophysiological disruptions induced by ketamine in animals, and the
      hippocampus may be one of the neural targets where CGP7930 exerts its actions.

PMID- 28756464
TI  - Socioeconomic patterning of chronic conditions and behavioral risk factors in
      rural South Asia: a multi-site cross-sectional study.
AB  - OBJECTIVES: Our aim was to examine relationships between markers of socioeconomic
      status and chronic disease risks in rural South Asia to understand the etiology
      of chronic diseases in the region and identify high-risk populations. METHODS: We
      examined data from 2271 adults in Chennai, Goa and Matlab sites of the Chronic
      Disease Risk Factor study in South Asia. We report age-sex adjusted odds ratios
      for risk factors (tobacco, alcohol, fruit-vegetable use and physical activity)
      and common chronic conditions (hypertension, diabetes, overweight, depression,
      impaired lung and vision) by education, occupation and wealth. RESULTS:
      Respondents with greater wealth and in non-manual professions were more likely to
      be overweight [OR = 2.48 (95% CI 1.8,3.38)] and have diabetes [OR = 1.88 (95% CI
      1.02,3.5)]. Wealth and education were associated with higher fruit and vegetable
      [OR = 1.89 (95% CI 1.48,2.4)] consumption but lower physical activity [OR = 0.52
      (95% CI 0.39,0.69)]. Non-manual workers reported lower tobacco and alcohol use,
      while wealthier respondents reported better vision and lung function.
      CONCLUSIONS: Ongoing monitoring of inequalities in chronic disease risks is
      needed for planning and evaluating interventions to address the growing burden of
      chronic conditions.

PMID- 28756465
TI  - Estimating lung cancer mortality attributable to second hand smoke exposure in
      Germany.
AB  - OBJECTIVES: Public health measures such as nonsmoker protection laws affect
      smoking prevalence and consequently the number of lung cancer deaths attributable
      to second hand smoke (SHS). In Germany, a risk assessment of SHS has been
      performed in 1994 only, and therefore, a reassessment is of interest. METHODS:
      Based on current knowledge on the relative risk of lung cancer from SHS, SHS
      prevalence, lung cancer deaths in Germany, and two approaches to estimate the
      number of never smokers among lung cancer deaths, we estimated the current number
      of deaths attributable to SHS among never smokers in Germany. RESULTS: Based on a
      relative risk of 1.21 (95% CI 1.14-1.28), recent prevalence of SHS of 39.5% for
      men and 23.5% for women, the attributable risks are 7.66 and 4.70%, respectively.
      Out of about 47,000 lung cancer deaths per year, the estimated number of never
      smokers is about 6000, out of which we estimated 167 being attributable to SHS.
      CONCLUSIONS: Despite an aging population, the number of deaths from lung cancer
      attributable to SHS decreased considerably. This positive trend should be
      strengthened by further public health measures.

PMID- 28756466
TI  - Anatomic and non-anatomic anterior cruciate ligament posterolateral bundle
      augmentation affects graft function.
AB  - PURPOSE: The purpose of this study is to compare knee laxity and graft function
      (tissue force) between anatomic and non-anatomic posterolateral (PL) bundle
      augmentation. METHODS: Twelve (n = 12) fresh-frozen mature, unpaired porcine
      knees were tested using a robotic testing system. Four knee states were compared:
      (a) intact anterior cruciate ligament (ACL), (b) deficient PL and intermediate
      bundles, (c) anatomic PL augmentation, and (d) non-anatomic PL augmentation.
      Anterior tibial translation (ATT), internal rotation (IR) and external rotation
      (ER), and the in situ tissue force were measured under an 89.0-N anterior tibial
      load and 4.0-N m internal and external tibial torques. RESULTS: Both anatomic and
      non-anatomic PL augmentation restored the ER, IR, and ATT of the intact knee at
      all knee flexion angles (n.s.). Both anatomic and non-anatomic PL augmentation
      restored the in situ tissue force of the ACL during ER and IR loading and ATT
      loading at all knee flexion angles except at 60 degrees  of knee flexion, where
      the non-anatomic PL augmentation did not restore the in situ tissue force of the
      ACL during external rotation loading and the anatomic PL augmentation did not
      restore the in situ tissue force of the ACL during IR loading. Furthermore, there
      were no differences in ATT, IR, ER, and in situ tissue force under anterior
      tibial loading, IR and ER loading between the two reconstruction groups.
      CONCLUSION: There were no significant differences between anatomic and non
      anatomic PL augmentation using the porcine knee model.

PMID- 28756467
TI  - No difference in graft healing or clinical outcome between trans-portal and
      outside-in techniques after anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to compare femoral tunnel geometry
      including tunnel position, length, and graft bending angle between trans-portal
      and outside-in techniques in anterior cruciate ligament (ACL) reconstruction and
      discover whether such differences in tunnel geometry could influence graft
      healing or clinical outcome. METHODS: Sixty-four patients with anatomical single
      bundle ACL reconstruction performed with either trans-portal technique (32
      patients, one centre) or outside-in technique (32 patients, the other centre)
      were included in this retrospective study. Femoral tunnel location and length,
      and graft bending angle at the femoral tunnel were analysed on 3D CT knee model.
      The location and length of the femoral tunnel and graft bending angle were
      compared between the two techniques. All patients underwent MRI scans at around 1
      year following ACL reconstruction. It was found that all patients had intact ACL
      graft on MRI images. On oblique axial image taken after ACL reconstruction to
      determine graft healing at femoral and tibial tunnels and the intra-articular
      portion, graft signal intensity ratio was calculated by dividing signal intensity
      (SI) of the reconstructed ACL by that of posterior cruciate ligament (PCL) in the
      region of interest selected with Marosis software. Clinical outcomes regarding
      Tegner activity scores, the International Knee Documentation Committee (IKDC)
      evaluation scores, Lachman test, and pivot shift test results were also compared
      between the two groups. RESULTS: While the location of femoral tunnel was similar
      to each other in both groups, the femoral tunnel length was longer in the outside
      in technique (37.0 vs. 32.4 mm, p = .02). Meanwhile, the outside-in technique
      showed significantly more acute graft tunnel angle than the trans-portal
      technique (106.7 degrees  vs. 113.8 degrees , p = .01). However, signal intensity
      ratios of grafts (compared with SI of PCL) were similar in femoral and tibial
      tunnels and intra-articular portions. Moreover, there were no statistically
      significant differences in terms of IKDC scores (89.4 vs. 90.5, n.s.) or Tegner
      activity scores (6.2 vs. 6.4, n.s.) between the two groups. There was no
      significant difference in measurement of Lachman or Pivot shift test either
      between the two groups. CONCLUSION: Even though the outside-in technique in ACL
      reconstruction created a more acute femoral graft bending angle and a longer
      femoral tunnel length than the trans-portal technique, these had no negative
      effect on graft healing. In addition, trans-portal and outside-in techniques in
      ACL reconstruction showed similar femoral tunnel positions and clinical outcomes.
      Acceptable graft healing and clinical outcomes can be obtained for both trans
      portal and outside-in techniques in ACL reconstruction. LEVEL OF EVIDENCE: III.

PMID- 28756469
TI  - Erratum to: Correlation between pre-injury mobility and ASA score with the
      mortality following femoral neck fracture in elderly.

PMID- 28756468
TI  - The impact of cognitive insight, self-stigma, and medication compliance on the
      quality of life in patients with schizophrenia.
AB  - Impaired quality of life (QoL) is a common and clinically relevant feature of
      schizophrenia. In the present study, we attempted to formulate a model of QoL in
      the chronic stage of schizophrenia by including key variables-namely cognitive
      insight, self-stigma, insight into treatment, and medication compliance-that were
      proposed as its significant predictors in previous studies. We employed
      structural equation modeling (SEM) to simultaneously test the associations
      between these variables. A total of 170 community-dwelling patients with
      schizophrenia participated in this study. Cognitive insight, self-stigma, insight
      into treatment, medication compliance, and QoL were assessed through self
      reporting. Symptoms were rated by interviewers. The influences of cognitive
      insight, stigma, insight into treatment, and medication compliance on QoL were
      supported using SEM. Our findings indicated that cognitive insight had a
      significant, positive, and direct effect on both self-stigma and insight into
      treatment; in contrast, it had a negative and direct effect on medication
      compliance. Notably, no evidence indicated a direct effect of cognitive insight
      on QoL. Thus, individuals with high cognitive insight reported low QoL because of
      stigma, low medication compliance, and their increased insight into treatment. In
      contrast, cognitive insight might indirectly ameliorate QoL mediated by the
      effect of insight into treatment on medication compliance. The findings provide
      additional support of the links between cognitive and clinical insight, self
      stigma, medication compliance, and QoL in those with schizophrenia and suggest
      the need for screening and intervention services appropriate for this high-risk
      population.

PMID- 28756470
TI  - A critical view on primary and secondary outcome measures in nutrition trials.

PMID- 28756473
TI  - Erratum to: HBV and HCV infection in type 2 diabetes mellitus: a survey in three
      diabetes units in different Italian areas.

PMID- 28756472
TI  - Totally implantable venous access ports: a prospective long-term study of early
      and late complications in adult patients with cancer.
AB  - PURPOSE: Totally implantable venous access ports (TIVAP) have been widely used
      for many years in the management of patients suffering from cancer. The
      implantation and long-term use of TIVAPs are associated with mechanical,
      thrombotic, and infectious complications. This is the first exhaustive
      prospective study of all complications occurring in a whole population on long
      term follow-up and therefore allows an objective assessment to be made of the
      safety of TIVAPs. METHODS: We carried out a prospective single-center
      observational study. All adult patients with cancer who had a TIVAP implanted
      between January 1 and December 31, 2006 were registered. Early and late
      complications were recorded until the removal of the device, the patient's death,
      or until December 31, 2013. Exhaustive data concerning patients and TIVAP was
      recorded at time of implantation. RESULTS: Four hundred and ninety-three TIVAPs
      were implanted in 483 adult cancer patients and were followed during a period
      from 1 to 94 months (median = 18 months) representing a global quantity of
      367,359 catheter-days. Eighty-seven complications were recorded (0.237/1000
      catheter-days), including 37 infections (0.101/1000 catheter-days), 17 thrombotic
      events (0.046/1000 catheter-days), and 9 extravasations. Out of the 87 events, 62
      (71.3%) occurred during the first year after implantation. Events were therefore
      extremely rare after 1 year. Thromboembolic and infectious complications were
      rare and no risk factors for these were found. CONCLUSIONS: This study
      demonstrates excellent tolerability, with only occasional complications. Most of
      these occurred during the year following implantation. A TIVAP may also be left
      in place for an extremely long time.

PMID- 28756471
TI  - The research agenda for trauma critical care.
AB  - In this research agenda on the acute and critical care management of trauma
      patients, we concentrate on the major factors leading to death, namely
      haemorrhage and traumatic brain injury (TBI). In haemostasis biology, the results
      of randomised controlled trials have led to the therapeutic focus moving away
      from the augmentation of coagulation factors (such as recombinant factor VIIa)
      and towards fibrinogen supplementation and administration of antifibrinolytics
      such as tranexamic acid. Novel diagnostic techniques need to be evaluated to
      determine whether an individualised precision approach is superior to current
      empirical practice. The timing and efficacy of platelet transfusions remain in
      question, while new blood products need to be developed and evaluated, including
      whole blood variants, lyophilised products and novel red cell storage modalities.
      The current cornerstones of TBI management are intracranial pressure control,
      maintenance of cerebral perfusion pressure and avoidance of secondary insults
      (such as hypotension, hypoxaemia, hyperglycaemia and pyrexia). Therapeutic
      hypothermia and decompressive craniectomy are controversial therapies. Further
      research into these strategies should focus on identifying which subgroups of
      patients may benefit from these interventions. Prediction of the long-term
      outcome early after TBI remains challenging. Early magnetic resonance imaging has
      recently been evaluated for predicting the long-term outcome in mild and severe
      TBI. Novel biomarkers may also help in outcome prediction and may predict chronic
      neurological symptoms. For trauma in general, rehabilitation is complex and
      multidimensional, and the optimal timing for commencement of rehabilitation needs
      investigation. We propose priority areas for clinical trials in the next 10
      years.

PMID- 28756474
TI  - Maternally inherited diabetes and deafness is a mitochondrial multiorgan disorder
      syndrome (MIMODS).

PMID- 28756475
TI  - Urine neutrophil gelatinase-associated lipocalin and other biomarkers in infants
      with urinary tract infection and in febrile controls.
AB  - BACKGROUND: Urine biomarkers are commonly used in the evaluation of acute kidney
      injury, and are gaining attention as tools for studying urinary tract infections
      (UTIs). We analyzed neutrophil gelatinase-associated lipocalin (NGAL) and seven
      other urine biomarkers to evaluate their usefulness in the diagnosis of UTI in
      infants. METHODS: Eight urine biomarkers were analyzed in 108 infants with UTI.
      Controls were 64 febrile children without UTI and 13 healthy children. Logistic
      regression and construction of receiver operating characteristic (ROC) curves
      were performed for UTI patients versus febrile controls for all biomarkers.
      RESULTS: The best biomarkers to differentiate between UTI and febrile controls
      were NGAL and interleukin 8 (IL8). Urine NGAL in absolute concentration and
      adjusted for creatinine had a sensitivity of 93% and 96% and a specificity of 95%
      and 100% for diagnosing UTI, with a cut-off concentration of 38 ng/mL and 233
      ng/mg respectively. CONCLUSIONS: Urine biomarkers, particularly NGAL, can aid in
      the diagnosis of UTI among febrile infants. The results suggest that in infants
      with fever and high NGAL, UTI is most likely, whereas in infants with fever and
      low NGAL, other causes of fever should be looked for.

PMID- 28756476
TI  - Development of Pyriform Sinus Suctioning Programs for Aspiration Pneumonia
      Prevention During the Acute Stroke.
AB  - Aspiration due to dysphagia is a factor associated with pneumonia during acute
      stroke. In such cases, it is likely that secretions in the pyriform sinuses enter
      the laryngeal inlet. The present study was based on the idea that it is possible
      to reduce aspiration pneumonia by periodically suctioning and removing such
      secretions (pyriform sinus suctioning), a study was conducted in a single
      facility. The incidence of pneumonia as a dependent variable was compared between
      before (control) and after (intervention group) intervention with pyriform sinus
      suctioning as an independent variable. With a view of unifying the quality and
      frequency of intervention, two programs to: initially confirm the safety of such
      suctioning; subsequently enhance/evaluate knowledge and skills related to the
      procedure (educational); and specify conditions for the implementation and
      criteria for determining its appropriateness (practical), were developed. The
      study involved 33 (mean age: 74.6 +/- 12.4) and 30 (80.0 +/- 8.8) control and
      intervention group members, respectively, 25 (83.3%) of the latter were treated
      with pyriform sinus suctioning for 5 days after a stroke. Pneumonia developed in
      7 (21.2%) and 2 (6.7%) of the former and latter, respectively. As individuals
      with a Japan Coma Scale (JCS) score of III or a midline shift on head CT tend to
      develop pharyngeal dysphagia, the patients were also divided into 2 groups to
      compare the incidence of pneumonia based on the risk level: low: Japan Coma Scale
      scores of I-II without a midline shift on head CT; and high: scores of II-III
      with it. In the latter, the incidence after intervention was markedly lower (p =
      0.06, phi = 0.326), while the former did not show changes (p = 0.574, phi =
      0.066), supporting the effectiveness of pyriform sinus suctioning to prevent
      aspiration pneumonia among patients with a low risk level.

PMID- 28756477
TI  - p53 signaling pathway polymorphisms, cancer risk and tumor phenotype in TP53
      R337H mutation carriers.
AB  - Li-Fraumeni and Li-Fraumeni-like syndrome (LFS/LFL) are clinically heterogeneous
      cancer predisposition syndromes characterized by diagnosis of early-onset and
      often multiple cancers with variable tumor patterns and incomplete penetrance. To
      date, the genetic modifiers described in LFS/LFL have been shown to map to either
      TP53 or its main negative regulator, MDM2. Additionally, all studies were focused
      on families with different TP53 germline mutations. Hence, in this study we
      explored the effect of the most studied polymorphisms of p53 pathway genes on
      clinical manifestations of individuals carrying the founder TP53 mutation R337H
      (n = 136) and controls (n = 186). Cancer-affected carriers had been diagnosed
      either with adrenocortical carcinoma (ACC, n = 29) or breast cancer (BC, n = 43).
      Allelic discrimation using TaqMan assay was used for genotyping MDM2 SNP 309
      (rs2279744) as well as MDM4 (rs1563828) and USP7 (rs1529916) polymorphisms. We
      found significantly higher MDM2 SNP 309 GG genotype and G allele frequencies in
      the LFS cohort than in controls. Furthermore, median age at first diagnosis was
      earlier in MDM2 SNP309 GG carriers when compared to other genotypes for both
      cancers (ACC: age 1 vs. 2 years; BC: age 35 vs. 43 years, respectively), although
      not statistically different. The allelic and genotypic frequencies for all SNPs
      did not differ between cancer affected and unaffected carriers, neither between
      patients with ACC or BC. In conclusion, our results suggest that MDM2 SNP 309 may
      contribute to the LFL phenotype and also to an earlier age at diagnosis of ACC
      and BC cancer in carriers of the R337H founder mutation.

PMID- 28756478
TI  - Protein 19F-labeling using transglutaminase for the NMR study of intermolecular
      interactions.
AB  - The preparation of stable isotope-labeled proteins is important for NMR studies,
      however, it is often hampered in the case of eukaryotic proteins which are not
      readily expressed in Escherichia coli. Such proteins are often conveniently
      investigated following post-expression chemical isotope tagging. Enzymatic 15N
      labeling of glutamine side chains using transglutaminase (TGase) has been applied
      to several proteins for NMR studies. 19F-labeling is useful for interaction
      studies due to its high NMR sensitivity and susceptibility. Here, 19F-labeling of
      glutamine side chains using TGase and 2,2,2-trifluoroethylamine hydrochloride was
      established for use in an NMR study. This enzymatic 19F-labeling readily provided
      NMR detection of protein-drug and protein-protein interactions with complexes of
      about 100 kDa since the surface residues provided a good substrate for TGase. The
      19F-labeling method was 3.5-fold more sensitive than 15N-labeling, and could be
      combined with other chemical modification techniques such as lysine 13C
      methylation. 13C-dimethylated-19F-labeled FKBP12 provided more accurate
      information concerning the FK506 binding site.

PMID- 28756479
TI  - Measurement Properties of the Modified Spinal Function Sort (M-SFS): Is It
      Reliable and Valid in Workers with Chronic Musculoskeletal Pain?
AB  - Purpose To analyze the reliability and validity of a picture-based questionnaire,
      the Modified Spinal Function Sort (M-SFS). Methods Sixty-two injured workers with
      chronic musculoskeletal disorders (MSD) were recruited from two work
      rehabilitation centers. Internal consistency was assessed by Cronbach's alpha.
      Construct validity was tested based on four a priori hypotheses. Structural
      validity was measured with principal component analysis (PCA). Test-retest
      reliability and agreement was evaluated using intraclass correlation coefficient
      (ICC) and measurement error with the limits of agreement (LoA). Results Total
      score of the M-SFS was 54.4 (SD 16.4) and 56.1 (16.4) for test and retest,
      respectively. Item distribution showed no ceiling effects. Cronbach's alpha was
      0.94 and 0.95 for test and retest, respectively. PCA showed the presence of four
      components explaining a total of 74% of the variance. Item communalities were
      >0.6 in 17 out of 20 items. ICC was 0.90, LoA was +/-12.6/16.2 points. The
      correlations between the M-SFS were 0.89 with the original SFS, 0.49 with the
      Pain Disability Index, -0.37 and -0.33 with the Numeric Rating Scale for actual
      pain, -0.52 for selfreported disability due to chronic low back pain, and 0.50,
      0.56-0.59 with three distinct lifting tests. No a priori defined hypothesis for
      construct validity was rejected. Conclusions The M-SFS allows reliable and valid
      assessment of perceived self-efficacy for work-related tasks and can be
      recommended for use in patients with chronic MSD. Further research should
      investigate the proposed M-SFS score of <56 for its predictive validity for non
      return to work.

PMID- 28756480
TI  - Validation of the Readiness for Return-To-Work Scale in Outpatient Occupational
      Rehabilitation in Canada.
AB  - Purpose To examine construct and concurrent validity of the Readiness for Return
      To-Work (RRTW) Scale with injured workers participating in an outpatient
      occupational rehabilitation program. Methods Lost-time claimants (n = 389) with
      sub-acute or chronic musculoskeletal disorders completed the RRTW Scale on their
      first day of their occupational rehabilitation program. Statistical analysis
      included exploratory and confirmatory factor analyses of the readiness items,
      reliability analyses, and correlation with related scales and questionnaires.
      Results For claimants in the non-job attached/not working group (n = 165), three
      factors were found (1) Contemplation (2) Prepared for Action-Self-evaluative and
      (3) Prepared for Action-Behavioural. The precontemplation stage was not
      identified within this sample of injured workers. For claimants who were job
      attached/working group in some capacity (n = 224), two factors were identified
      (1) Uncertain Maintenance and (2) Proactive Maintenance. Expected relationships
      and statistically significant differences were found among the identified Return
      To-Work (RTW) readiness factors and related constructs of pain, physical and
      mental health and RTW expectations. Conclusion Construct and concurrent validity
      of the RRTW Scale were supported in this study. The results of this study
      indicate the construct of readiness for RTW can vary by disability duration and
      occupational category. Physical health appears to be a significant barrier to
      RRTW for the job attached/working group while mental health significantly
      compromises RRTW with the non-job attached/not working group.

PMID- 28756481
TI  - Biologically relevant conformational features of linear and cyclic proteolipid
      protein (PLP) peptide analogues obtained by high-resolution nuclear magnetic
      resonance and molecular dynamics.
AB  - Proteolipid protein (PLP) is one of the main proteins of myelin sheath that are
      destroyed during the progress of multiple sclerosis (MS). The immunodominant
      PLP139-151 epitope is known to induce experimental autoimmune encephalomyelitis
      (EAE, animal model of MS), wherein residues 144 and 147 are recognized by T cell
      receptor (TCR) during the formation of trimolecular complex with peptide-antigen
      and major histocompability complex. The conformational behavior of linear and
      cyclic peptide analogues of PLP, namely PLP139-151 and cyclic (139-151) (L144,
      R147) PLP139-151, have been studied in solution by means of nuclear magnetic
      resonance (NMR) methods in combination with unrestrained molecular dynamics
      simulations. The results indicate that the side chains of mutated amino acids in
      the cyclic analogue have different spatial orientation compared with the
      corresponding side chains of the linear analogue, which can lead to reduced
      affinity to TCR. NMR experiments combined with theoretical calculations pave the
      way for the design and synthesis of potent restricted peptides of immunodominant
      PLP139-151 epitope as well as non peptide mimetics that rises as an ultimate
      goal.

PMID- 28756482
TI  - EPR Oximetry of Cetuximab-Treated Head-and-Neck Tumours in a Mouse Model.
AB  - Head and neck squamous cell carcinoma (HNSCC) tumours are associated with high
      mortality despite advances in therapy. The monoclonal antibody cetuximab
      (Erbitux(r)) has been approved for the treatment of advanced HNSCC. However, only
      a subset of HNSC patients receiving cetuximab actually responds to treatment,
      underlining the need for a means to tailor treatments of individual patients. The
      aim of the present study was to investigate the effect of cetuximab treatment on
      tumour growth, on tumour partial oxygen pressure as measured by LiPc electron
      paramagnetic resonance oximetry and on the expression of proteins involved in
      tumour growth, metabolism and hypoxia. Two HNSCC cell lines, UT-SCC-2 and UT-SCC
      14, were used to generate xenografts on female BALB/c (nu/nu) nude mice. Mice
      with xenografts were given three injections of intraperitoneal cetuximab or
      phosphate-buffered saline, and the tumour volume was recorded continuously. After
      treatment the tumour partial oxygen pressure was measured by LiPc electron
      paramagnetic resonance oximetry and the expression of epidermal growth factor
      receptor (EGFR), phosphorylated EGFR, Ki-67, MCT1, MCT4, GLUT1, CAIX and HIF
      1alpha were investigated by immunohistochemistry. In xenografts from both cell
      lines (UT-SCC-2 and UT-SCC-14) cetuximab had effect on the tumour volume but the
      effect was more pronounced on UT-SCC-14 xenografts. A higher tumour oxygenation
      was measured in cetuximab-treated tumours from both cell lines compared to
      untreated controls. Immunocytochemical staining after cetuximab treatment shows a
      significantly decreased expression of EGFR, pEGFR, Ki67, CAIX and nuclear HIF
      1alpha in UT-SCC-14 tumours compared to untreated controls. MCT1 and GLUT1 were
      significantly decreased in tumours from both cell lines but more pronounced in UT
      SCC-14 tumours. Taken together, our results show that cetuximab treatment
      decreases the tumour growth and increases the tumour partial oxygen pressure of
      HNSCC xenografts. Furthermore we found a potential connection between the partial
      oxygen pressure of the tumours and the expression of proteins involved in tumour
      growth, metabolism and hypoxia.

PMID- 28756483
TI  - Identification of Structure-Stabilizing Interactions in Enzymes: A Novel
      Mechanism to Impact Enzyme Activity.
AB  - Cruzain, a cysteine protease in the cathepsin family, is pivotal to the life
      cycle of Trypanosoma cruzi, the etiological agent in Chagas disease. Current
      inhibitors of cruzain suffer from drawbacks involving gastrointestinal and
      neurological side effects and as a result have spurred the search for alternative
      anti-trypanocidals. Through sequence alignment studies and intra-residue
      interaction analysis of the pro-protein of cruzain (pro-cruzain), we have
      identified a host of non-active site residues that are conserved among the
      cathepsins. We hypothesize that these conserved amino acids play a critical role
      in structure-stabilizing interactions among the cathepsins and are therefore
      crucial for eventually gaining protease activity. As predicted, mutation of
      selected conserved non-active site amino-acid candidates in cruzain resulted in a
      compromised structural stability and a corresponding loss in enzymatic activity
      relative to wild-type enzyme. By advancing the discovery of novel, non-active
      site-based targets to arrest enzymatic activity our results potentially open the
      field of alternative inhibitor design. The advantages of defining such a non
      active-site inhibitor design space is discussed.

PMID- 28756484
TI  - Distal esophageal spasm with multiple esophageal diverticula successfully treated
      by peroral endoscopic myotomy.
AB  - Distal esophageal spasm (DES) is a primary esophageal motility disorder. We
      encountered a rare case of DES accompanied by multiple esophageal diverticula. A
      72-year-old woman complained of prolonged dysphagia and chest pain. A barium
      esophagogram showed multiple esophageal diverticula and significant contraction
      of the lower esophagus just above the cardia. Esophagogastroduodenoscopy revealed
      a corkscrew-like appearance, with spiral contractions and diverticula. High
      resolution manometry revealed that the integrated relaxation pressure was normal;
      premature contractions were observed in >=20% of the swallowing wave; the distal
      contractile integral was normal. She was diagnosed with DES according to the
      Chicago classification v 3.0. As smooth muscle relaxants were not effective, we
      decided to perform peroral endoscopic myotomy (POEM) to eliminate persistent
      esophageal contraction. After POEM treatment, her symptoms were markedly
      improved, and the Eckardt score significantly decreased from 11 points to 1. An
      esophagogram after POEM showed that barium flowed promptly into the stomach. The
      multiple esophageal diverticula were considered to be the result of false pulsion
      diverticulosis caused by excessive internal esophageal pressure, and this
      represented the most severe form of DES. POEM could be a new curative strategy
      for the most severe DES cases with multiple diverticula.

PMID- 28756485
TI  - Laterality of anterior temporal lobe repetitive transcranial magnetic stimulation
      determines the degree of disruption in picture naming.
AB  - The bilateral anterior temporal lobes play a key role in semantic representation.
      This is clearly demonstrated by the performance of patients with semantic
      dementia, a disorder characterised by a progressive and selective decline in
      semantic memory over all modalities as a result of anterior temporal atrophy.
      Although all patients exhibit a progressive decline in both single-word
      production and comprehension, those with greater atrophy to the left anterior
      temporal lobe show a stronger decline in word production than comprehension. This
      asymmetry has been attributed to the greater connectivity of the left anterior
      temporal lobe with left-lateralised speech production mechanisms. Virtual
      lesioning of the left ATL using offline repetitive transcranial magnetic
      stimulation (rTMS) has been shown to disrupt picture naming, but, the impact of
      right ATL rTMS is yet to be explored. We tested the prediction that disruption of
      picture naming in normal participants by rTMS should be greater for the left than
      the right ATL. We found a significant increase in picture naming latencies
      specifically for stimulation of the left ATL only. Neither left nor right ATL TMS
      slowed performance in a number naming control task. These results support the
      hypothesis that although both temporal lobes are part of a widespread semantic
      network in the human brain, the left anterior temporal lobe possesses a stronger
      connection to left-lateralised speech production areas than the right temporal
      lobe.

PMID- 28756487
TI  - Anatomo-functional correspondence in the superior temporal sulcus.
AB  - The superior temporal sulcus (STS) is an intriguing region both for its complex
      anatomy and for the multiple functions that it hosts. Unfortunately, most studies
      explored either the functional organization or the anatomy of the STS only. Here,
      we link these two aspects by investigating anatomo-functional correspondences
      between the voice-sensitive cortex (Temporal Voice Areas) and the STS depth. To
      do so, anatomical and functional scans of 116 subjects were processed such as to
      generate individual surface maps on which both depth and functional voice
      activity can be analyzed. Individual depth profiles of manually drawn STS and
      functional profiles from a voice localizer (voice > non-voice) maps were
      extracted and compared to assess anatomo-functional correspondences. Three major
      results were obtained: first, the STS exhibits a highly significant rightward
      depth asymmetry in its middle part. Second, there is an anatomo-functional
      correspondence between the location of the voice-sensitive peak and the deepest
      point inside this asymmetrical region bilaterally. Finally, we showed that this
      correspondence was independent of the gender and, using a machine learning
      approach, that it existed at the individual level. These findings offer new
      perspectives for the understanding of anatomo-functional correspondences in this
      complex cortical region.

PMID- 28756486
TI  - Cortical morphology of the pars opercularis and its relationship to motor
      inhibitory performance in a longitudinal, developing cohort.
AB  - This study investigates the relationship between variability in cortical surface
      area and thickness of the pars opercularis of the inferior frontal gyrus and
      motor-inhibitory performance on a stop-signal task in a longitudinal, typically
      developing cohort of children and adolescents. Linear mixed-effects models were
      used to investigate the hypotheses that (1) cortical thinning and (2) a
      relatively larger cortical surface area of the bilateral pars opercularis of the
      inferior frontal gyrus would predict better performance on the stop-signal task
      in a cohort of 110 children and adolescents 4-13 years of age, with one to four
      observations (totaling 232 observations). Cortical thickness of the bilateral
      opercular region was not related to inhibitory performance. However, independent
      of age, gender, and total cortical surface area, relatively larger cortical
      surface area of the bilateral opercular region of the inferior frontal gyrus was
      associated with better motor-inhibitory performance. Follow-up analyses showed a
      significant effect of surface area of the right pars opercularis, but no evidence
      for an effect of area of left pars opercularis, on motor-inhibitory performance.
      These findings are consistent with the previous work in adults showing that
      cortical morphology of the pars opercularis is related to inhibitory functioning.
      It also expands upon this literature by showing that, in contrast to earlier work
      highlighting the importance of cortical thickness of this region in adults,
      relative cortical surface area of the pars opercularis may be related to
      developing motor-inhibitory functions during childhood and adolescence.
      Relationships between cortical phenotypes and individual differences in
      behavioral measures may vary across the lifespan.

PMID- 28756488
TI  - Advancement of spring arrival in a long-term study of a passerine bird: sex, age
      and environmental effects.
AB  - In migratory birds, mistimed arrival might have negative consequences for
      individual fitness, causing population declines. This may happen if arrival time
      is not synchronized with breeding time, especially when earlier springs favour
      earlier reproduction. We studied spring arrival time to the breeding areas in a
      pied flycatcher Ficedula hypoleuca population in southern Norway during a 30-year
      period (1985-2014). We investigated trends in arrival both for the entire
      population and for different population fractions (e.g. early vs. late arrivals).
      We also studied sex and age class differences, along with repeatability of
      arrival. Finally, we explored how arrival is influenced by environmental
      conditions at the areas birds use throughout the year, using mixed-effects models
      and quantile regressions with individual-based data. Spring arrival advanced over
      five days, at a similar rate through the entire population. Males and adult birds
      arrived earlier than females and yearlings. Arrival was significantly repeatable
      for males and females. Birds arrived earlier in years with high temperature and
      rainfall at the breeding grounds, and low NDVI both on the Iberian Peninsula and
      in central Europe. Later fractions of the population showed a steeper response to
      these environmental variables. This intra-population heterogeneity in the
      responses to the environment probably stems from a combination between the
      different selection pressures individuals are subject to and their age-related
      experience. Our results highlight the importance of studying how migration
      phenology is affected by the environment not only on the breeding grounds but
      also on the other areas birds use throughout the year.

PMID- 28756489
TI  - How does synchrony with host plant affect the performance of an outbreaking
      insect defoliator?
AB  - Phenological mismatch has been proposed as a key mechanism by which climate
      change can increase the severity of insect outbreaks. Spruce budworm
      (Choristoneura fumiferana) is a serious defoliator of North American conifers
      that feeds on buds in the early spring. Black spruce (Picea mariana) has
      traditionally been considered a poor-quality host plant since its buds open later
      than those of the preferred host, balsam fir (Abies balsamea). We hypothesize
      that advancing black spruce budbreak phenology under a warmer climate would
      improve its phenological synchrony with budworm and hence increase both its
      suitability as a host plant and resulting defoliation damage. We evaluated the
      relationship between tree phenology and both budworm performance and tree
      defoliation by placing seven cohorts of budworm larvae on black spruce and balsam
      fir branches at different lags with tree budburst. Our results show that on both
      host plants, spruce budworm survival and pupal mass decrease sharply when
      budbreak occurs prior to larval emergence. By contrast, emergence before budbreak
      decreases survival, but does not negatively impact growth or reproductive output.
      We also document phytochemical changes that occur as needles mature and define a
      window of opportunity for the budworm. Finally, larvae that emerged in synchrony
      with budbreak had the greatest defoliating effect on black spruce. Our results
      suggest that in the event of advanced black spruce phenology due to climate
      warming, this host species will support better budworm survival and suffer
      increased defoliation.

PMID- 28756490
TI  - Age-specific patterns of infection with haemosporidians and trypanosomes in a
      warbler: implications for sexual selection.
AB  - Although the selective loss of individuals susceptible to disease can favor the
      evolution of female preference for older males, the interrelationship between
      age, infection, longevity, and mating success remains poorly characterized in
      natural populations. In a longitudinal study of 61 male common yellowthroats
      (Geothlypis trichas), we found that the probability of infection with hematozoa
      increased as males aged from 1 to 5 years. Despite a significant, negative
      association between infection and longevity that partially masked age-effects,
      the odds that a male was infected with Trypanosoma, Plasmodium, or Leucocytozoon
      increased 71-212% per year. Nearly 75% of males in their first breeding season
      were either uninfected or infected with only a single parasite, while 50% of
      older males were infected with at least two parasites and 16% were infected with
      all three. No males escaped infection after their second breeding season. Older
      males were also more likely to sire extra-pair young (EPY) and, as a consequence,
      infection with multiple parasites was associated with a fourfold increase in the
      odds of producing EPY. Unlike younger males, 80% of the oldest males had a
      history of either surviving chronic infection or recovering. Combined with
      previous work showing higher diversity at the major histocompatibility complex
      among older males, our results suggest that the song and plumage traits that
      signal male age in common yellowthroats also, perforce, signal resistance to
      parasites. By preferring older males, females may obtain good genes for disease
      resistance even in the absence of any effect of infection on male ornamentation.

PMID- 28756491
TI  - Nitrogen effects on the pelagic food web are modified by dissolved organic
      carbon.
AB  - Global environmental change has altered the nitrogen (N) cycle and enhanced
      terrestrial dissolved organic carbon (DOC) loadings to northern boreal lakes.
      However, it is still unclear how enhanced N availability affects pelagic food web
      efficiency (FWE) and crustacean zooplankton growth in N limited boreal lakes.
      Here, we performed in situ mesocosm experiments in six unproductive boreal
      Swedish lakes, paired across a DOC gradient, with one lake in each pair
      fertilized with N (2011: reference year; 2012, 2013: impact years). We assessed
      how zooplankton growth and FWE were affected by changes in pelagic energy
      mobilization (PEM), food chain length (phytoplankton versus bacterial production
      based food chain, i.e. PP:BP), and food quality (seston stoichiometry) in
      response to N fertilization. Although PP, PEM and PP:BP increased in low and
      medium DOC lakes after N fertilization, consumer growth and FWE were reduced,
      especially at low DOC-potentially due to reduced phytoplankton food quality
      [increased C: phosphorus (P); N:P]. At high DOC, N fertilization caused modest
      increases in PP and PEM, with marginal changes in PP:BP and phytoplankton food
      quality, which, combined, led to a slight increase in zooplankton growth and FWE.
      Consequently, at low DOC (<12 mg L-1), increased N availability lowers FWE due to
      mismatches in food quality demand and supply, whereas at high DOC this mismatch
      does not occur, and zooplankton production and FWE may increase. We conclude that
      the lake DOC level is critical for predicting the effects of enhanced inorganic N
      availability on pelagic productivity in boreal lakes.

PMID- 28756492
TI  - Large-scale comprehensive immunohistochemical biomarker analyses in esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a heterogeneous disease
      in the sense that the biological behavior is regulated by the activation of
      various signaling pathways. The aim of this study was to investigate the
      relationships between the expressions of various targetable proteins and the
      clinicopathological characteristics of ESCC patients. METHODS: A total of 286
      patients with ESCC who had undergone curative surgical resection without
      neoadjuvant therapy were enrolled in this study. The protein expressions of EGFR,
      HER2, MET, IGF1R, FGFR2, p53, and PD-L1 were immunohistochemically evaluated in a
      tissue microarray analysis. The relationships between the expression statuses of
      each of the above molecules, and the PD-L1 expression status as well as the
      clinicopathological characteristics, including the survival outcome were
      assessed. RESULTS: The expression frequencies of EGFR, HER2, MET, IGF1R, FGFR2,
      p53, and PD-L1 were as follows: 90.9, 1.0, 2.4, 71.0, 16.1, 62.9 and 23.4%. The
      overlapping expressions of two or more receptor tyrosine kinases were observed in
      72.0%. MET expression was the only poor prognostic factor of recurrence-free
      survival [hazard ratio (HR) 1.89, 95% confidence interval (CI) 1.15-3.11]; in
      contrast, PD-L1 was the only favorable prognostic factor for both recurrence-free
      survival (HR 0.57, 95% CI 0.38-0.87) and overall survival (HR 0.56, 95% CI 0.35
      0.89). No correlation was observed between the expressions of PD-L1 and the other
      molecules. CONCLUSIONS: This large cohort study demonstrated that multiple
      molecules were co-expressed in most of the ESCC cases, suggesting that combining
      molecular targeted agents for these co-expressed molecules should be considered.

PMID- 28756494
TI  - Usability Evaluation of a Private Social Network on Mental Health for Relatives.
AB  - Usability is one of the most prominent criteria that must be fulfilled by a
      software product. This study aims to evaluate the usability of SocialNet, a
      private social network for monitoring the daily progress of patients by their
      relatives, using a mixed usability approach: heuristic evaluation conducted by
      experts and user testing. A double heuristic evaluation with one expert evaluator
      identified the issues related to consistency, design, and privacy. User testing
      was conducted on 20 users and one evaluator using observation techniques and
      questionnaires. The main usability problems were found to be related to the
      structure of SocialNet, and the users presented some difficulties in locating the
      buttons or links. The results show a high level of usability and satisfaction
      with the product. This evaluation provides data on the usability of SocialNet
      based on the difficulties experienced by the users and the expert. The results
      help in redesigning the tool to resolve the identified problems as part of an
      iterative process.

PMID- 28756493
TI  - Impact of adjuvant chemotherapy after neoadjuvant radio- or radiochemotherapy for
      patients with locally advanced rectal cancer.
AB  - BACKGROUND: Due to its primarily extraperitoneal location, potential affection of
      the anorectal continence and different metastatic behavior the rectal carcinoma
      (RC) is classified and treated as an independent disease. Over the past few
      decades various trials have led to improved multimodal therapies (including
      radiation, chemotherapy and surgery) for locally advanced rectal cancer and
      significant changes in the management of this disease whereas the benefit of
      adjuvant chemotherapy remains unclear. METHODS: Based on a prospective tumor
      register of the University Hospital of Wuerzburg data of 263 patients having
      undergone neoadjuvant therapy and surgical resection for locally advanced rectal
      cancer were retrieved from the Wuerzburg International database (WID) between
      October 1992 and September 2013 analyzing the overall survival according to the
      application of an adjuvant therapy. RESULTS: The cohort consisted of 263 patients
      with a median age of 65 years (27-89 years), mostly male gender (n = 191; 72.6%)
      and an ASA performance score of II or III. 143 patients (54.3%) received an
      adjuvant therapy. Those patients have been significant younger (median 10 years;
      p < 0.05) and in a better general condition (ASA-score; p < 0.05). The tumor
      specific overall survival of adjuvant treated patients was significant better (5
      years overall-survival 87.4%; p = 0.025) than the surveillance group. In the
      performed subgroup analysis no significant differences in overall survival
      according to the kind of neoadjuvant therapy (radiation vs. radiochemotherapy)
      have been found whereas patients in lower UICC-stages (ypUICC 0 + I) had a
      significant benefit by receiving a postoperative chemotherapy (p = 0.035).
      CONCLUSION: We considered patients with locally advanced rectal cancer have a
      significant benefit in overall survival by receiving an adjuvant chemotherapy
      especially in lower pathological tumor stage (ypUICC 0 + I). Especially because
      of the heterogeneity of our study population prospective randomized trials are
      necessary to determine the impact of adjuvant chemotherapy for locally advanced
      rectal cancer.

PMID- 28756495
TI  - Percutaneous dilatational tracheostomy using the ETView Tracheoscopic Ventilation
      Tube(r): a teaching course in a pig model.
AB  - OBJECTIVE: We planned a training course for trainees of different specialties
      with the aim of teaching the skills of a new procedure for performing
      percutaneous dilatational tracheostomy (PDT) with an ETView tracheoscopic
      ventilation tube instead of standard bronchoscopy in an ex vivo pig model.
      METHODS: The endotracheal tube, with a camera-embedded tip, was used as an
      alternative to standard bronchoscopy for visualization of patient airways. The
      procedure was performed on a home-made animal model. The participants were asked
      to perform PDT in three different sessions to improve their dexterity. The
      primary endpoint was the reduction of complications seen during the different
      sessions of the training course. The secondary endpoint was the satisfaction of
      the participants as assessed by an anonymous survey. RESULTS: Thirty-seven
      residents in anesthesiology and 7 in thoracic surgery in the first 2 years of
      their training and without any confidence with percutaneous tracheostomy
      participated in the study. Tracheal cuff lesions and impalement of the tracheal
      tube were the most observed complications, and were concentrated in the early
      sessions. A significant reduction in complications and operative time was seen
      during the ongoing sessions of the course. No lesions of the posterior tracheal
      wall and only a ring fracture occurred during the last session of the course. All
      participants were satisfied with the course. CONCLUSIONS: Our course seems to
      confer the technical skills to perform percutaneous tracheostomy to trainees and
      instill confidence with the procedure. However, the experience acquired on a
      training course should be evaluated in clinical practice.

PMID- 28756496
TI  - Cryopreservation of human ovarian tissue using the silver closed vitrification
      system.
AB  - PURPOSE: The aim of this study is to evaluate the feasibility of using a hand
      made silver container for the cryopreservation of human ovarian cortex. METHODS:
      Human ovarian cortex tissues were vitrified using an open vitrification system
      (OVS) of needle immersed vitrification (NIV) and two closed vitrification systems
      (CVS) of a plastic vial (plastic CVS) and a silver container (silver CVS).
      Outcomes of vitrification were evaluated morphologically and histologically by in
      vitro culture and xenotransplantation. The apoptosis of primordial follicles was
      assessed by TUNEL staining. The production of E2 and P4 was examined by a
      chemiluminescent immunoassay. Blood vessels were visualized with CD31 staining.
      RESULTS: Compared with the fresh ovarian cortex tissue, ovarian cortex tissues
      that were vitrified using the three different carriers and then warmed showed
      significantly reduced percentages of normal primordial follicles, viability of
      primordial follicles, E2 and P4 levels during in vitro culture and decreased
      amounts of blood vessels. However, much better outcomes were obtained with NIV
      and silver CVS than with plastic CVS, based on the better morphology and
      viability of primordial follicles, higher E2 and P4 production during an in vitro
      culture, and greater numbers of blood vessels after xenografting. Importantly,
      the outcomes of ovarian cortex cryopreservation with silver CVS were similar and
      comparable to those with NIV. CONCLUSIONS: The hand-made silver container as a
      CVS is a promising carrier for the cryopreservation of the human ovarian cortex.

PMID- 28756497
TI  - Natural selection between day 3 and day 5/6 PGD embryos in couples with
      reciprocal or Robertsonian translocations.
AB  - PURPOSE: For translocation carriers, preimplantation genetic diagnosis (PGD)
      provides the opportunity to distinguish between normal/balanced and unbalanced
      embryos prior to implantation and, as such, increases the likelihood of a
      successful ongoing pregnancy. The data presented here compares autosomal
      reciprocal and Robertsonian translocation segregation patterns in day 3 versus
      day 5/6 IVF-PGD embryos to determine if there is a difference in the chromosome
      segregation patterns observed at these developmental time points. METHODS: A
      retrospective analysis on PGD translocation carriers at Monash IVF was performed.
      Segregation patterns were compared between day 3 and day 5/6 embryos to ascertain
      whether selection against malsegregants exists. RESULTS: For reciprocal
      translocations, 1649 day 3 embryos (139 translocations) from 144 couples and 128
      day 5/6 embryos (59 translocations) from 60 couples were analysed. Day 3
      segregation analysis showed that 22.3% of embryos were normal/balanced
      (consistent with 2:2 alternate segregation) and 77.7% were unbalanced
      (malsegregation). Day 5/6 segregation analysis showed that 53.1% of embryos were
      normal/balanced and 46.9% were unbalanced. For Robertsonian translocations, 847
      day 3 embryos (8 translocations) from 54 couples and 193 day 5/6 embryos (6
      translocations) from 31 couples were analysed. Day 3 segregation analysis showed
      that 38.7% of embryos were normal/balanced (consistent with 2:1 alternate
      segregation) and 61.3% were unbalanced. Day 5/6 segregation analysis showed that
      74.1% of embryos were normal/balanced and 25.9% were unbalanced. CONCLUSIONS:
      This data demonstrates an increase in the proportion of genetically
      normal/balanced embryos at day 5/6 of development. This suggests a strong natural
      selection process between day 3 and day 5/6 in favour of normal/balanced embryos.
      These findings support performing PGD testing on day 5/6 of embryo development.

PMID- 28756499
TI  - Ocular loiasis in Ohio: a case report.

PMID- 28756498
TI  - Post-transplant erythrocytosis-related maculopathy: successful management of
      hyperviscosity with phlebotomy.
AB  - PURPOSE: To report clinical features in a case of hyperviscosity retinopathy
      following post-renal transplant erythrocytosis (PTE) and its outcome after
      phlebotomy. METHODS: Fundus fluorescein angiography and optical coherence
      tomography (OCT) were carried out for a 29-year-old renal allograft recipient who
      presented with acute unilateral visual loss. RESULT: There was mild retinal
      vascular dilation in both eyes with retinal hemorrhages and retinal opaqueness in
      left eye. Cystoid macular edema was noted on OCT. Microvascular leaks and micro
      occlusions were seen all around the foveal avascular zone on fluorescein
      angiogram. Investigations revealed hemoglobin to be 16.8 g%, and a PTE was
      diagnosed. The patient underwent phlebotomy following which there was near
      complete resolution of macular edema with improvement in vision. CONCLUSION:
      Hyperviscosity retinopathy can cause acute visual loss in cases of renal
      allograft recipients who develop PTE. Prompt management with phlebotomy can lead
      to reversal of macular edema in such cases.

PMID- 28756500
TI  - The Role of Attachment and Maladaptive Emotion Regulation Strategies in the
      Development of Bulimic Symptoms in Adolescents.
AB  - Following the theoretical propositions of the Emotion Regulation model of
      attachment, the current study investigated whether attachment anxiety and
      attachment avoidance might play a differential contributing role in the
      development of bulimic symptoms, through assumed differences in adopting specific
      maladaptive emotion regulation strategies in a sample of adolescents.
      Developmentally appropriate self-report questionnaires were administered to a
      community sample of 397 adolescents (Mean age: 14.02; 62.7% female) and this at 2
      time points with a 1-year time lag. Results provided longitudinal evidence for
      the Emotion Regulation model of attachment in confirming the differential
      contributing role of the attachment dimensions on the development of bulimic
      symptoms in a sample of adolescents. More specifically, attachment anxiety seemed
      to be related to bulimic symptoms through rumination, while attachment avoidance
      through emotional control. These results may have clinical implications for
      assessment and treatment of bulimic symptoms in adolescents.

PMID- 28756501
TI  - Cognitive Characteristics of Strategic and Non-strategic Gamblers.
AB  - Participation in strategic and non-strategic games is mostly explained in the
      literature by gender: men gamble on strategic games, while women gamble on non
      strategic games. However, little is known about the underlying cognitive factors
      that could also distinguish strategic and non-strategic gamblers. We suggest that
      cognitive style and need for cognition also explain participation in gambling
      subtypes. From a dual-process perspective, cognitive style is the tendency to
      reject or accept the fast, automatic answer that comes immediately in response to
      a problem. Individuals that preferentially reject the automatic response use an
      analytic style, which suggest processing information in a slow way, with deep
      treatment. The intuitive style supposes a reliance on fast, automatic answers.
      The need for cognition provides a motivation to engage in effortful activities.
      One hundred and forty-nine gamblers (53 strategic and 96 non-strategic) answered
      the Cognitive Reflection Test, Need For Cognition Scale, and socio-demographic
      questions. A logistic regression was conducted to evaluate the influence of
      gender, cognitive style and need for cognition on participation in strategic and
      non-strategic games. Our results show that a model with both gender and cognitive
      variables is more accurate than a model with gender alone. Analytic (vs.
      intuitive) style, high (vs. low) need for cognition and being male (vs. female)
      are characteristics of strategic gamblers (vs. non-strategic gamblers). This
      study highlights the importance of considering the cognitive characteristics of
      strategic and non-strategic gamblers in order to develop preventive campaigns and
      treatments that fit the best profiles for gamblers.

PMID- 28756502
TI  - Aciduric Strains of Lactobacillus reuteri and Lactobacillus rhamnosus, Isolated
      from Human Feces, Have Strong Adhesion and Aggregation Properties.
AB  - Human feces were streaked onto MRS Agar adjusted to pH 2.5, 3.0, and 6.4,
      respectively, and medium supplemented with 1.0% (w/v) bile salts. Two aciduric
      strains, identified as Lactobacillus reuteri HFI-LD5 and Lactobacillus rhamnosus
      HFI-K2 (based on 16S rDNA and recA sequences), were non-hemolytic and did not
      hydrolyze mucin. The surface of Lactobacillus reuteri HFI-LD5 cells has a weak
      negative charge, whereas Lactobacillus rhamnosus HFI-K2 has acidic and basic
      properties, and produces exopolysaccharides (EPS). None of the strains produce
      bacteriocins. Both strains are resistant to several antibiotics, including
      sulfamethoxazole-trimethoprim and sulphonamides. The ability of Lactobacillus
      reuteri HFI-LD5 and Lactobacillus rhamnosus HFI-K2 to grow at pH 2.5 suggests
      that they will survive passage through the stomach. EPS production may assist in
      binding to intestinal mucus, especially in the small intestinal tract, protect
      epithelial cells, and stimulate the immune system. Lactobacillus reuteri HFI-LD5
      and Lactobacillus rhamnosus HFI-K2 may be used as probiotics, especially in the
      treatment of small intestinal bacterial overgrowth (SIBO).

PMID- 28756503
TI  - Gestational Age and Sex Influence the Susceptibility of Human Neural Progenitor
      Cells to Low Levels of MeHg.
AB  - The developing nervous system is highly susceptible to methylmercury (MeHg), a
      widespread environmental neurotoxic contaminant. A wide range of morphological
      and functional outcomes have been described; however, there are still open
      questions regarding the mechanisms behind the developmental neurotoxic effects
      induced by low-level exposure. In the present study, we have examined the effects
      of nanomolar concentrations of MeHg on primary fetal human progenitor cells
      (hNPCs) with special focus on the role played by developmental stage and sex on
      the neurotoxic outcome. We found that neurospheres derived from earlier
      gestational time points exhibit higher susceptibility to MeHg, as they undergo
      apoptosis at a much lower dose (25 nM) as compared to neurospheres established
      from older fetuses (100 nM). At subapoptotic concentrations (10 nM), MeHg
      inhibited neuronal differentiation and maturation of hNPCs, as shown by a reduced
      number of Tuj1-positive cells and a visible reduction in neurite extension and
      cell migration, associated with a misregulation of Notch1 and BDNF signaling
      pathways. Interestingly, cells derived from male fetuses showed more severe
      alterations of neuronal morphology as compared to cells from females, indicating
      that the MeHg-induced impairment of neurite extension and cell migration is sex
      dependent. Accordingly, the expression of the CDKL5 gene, a major factor
      regulating neurite outgrowth, was significantly more downregulated in male
      derived cells. Altogether, gestational age and sex appear to be critical factors
      influencing in vitro hNPC sensitivity to low levels of MeHg.

PMID- 28756505
TI  - Perforated mitral valve aneurysm diagnosed 3 years after etiology-unknown
      iliopsoas muscle abscess: illustrative case of 'self-attack' endocarditis of the
      mitral valve.

PMID- 28756504
TI  - The Relational Impact of Multiple Sclerosis: An Integrative Review of the
      Literature Using a Cognitive Analytic Framework.
AB  - This integrative literature review uses cognitive analytic therapy (CAT) theory
      to examine the impact of a chronic illness, multiple sclerosis (MS), on
      relationships and mental health. Electronic searches were conducted in six
      medical and social science databases. Thirty-eight articles met inclusion
      criteria, and also satisfied quality criteria. Articles revealed that MS-related
      demands change care needs and alter relationships. Using a CAT framework, the MS
      literature was analysed, and five key patterns of relating to oneself and to
      others were identified. A diagrammatic formulation is proposed that interconnects
      these patterns with wellbeing and suggests potential "exits" to improve mental
      health, for example, assisting families to minimise overprotection. Application
      of CAT analysis to the literature clarifies relational processes that may affect
      mental health among individuals with MS, which hopefully will inform how services
      assist in reducing unhelpful patterns and improve coping. Further investigation
      of the identified patterns is needed.

PMID- 28756506
TI  - High- and low-Molecular Weight oat Beta-Glucan Reveals Antitumor Activity in
      Human Epithelial Lung Cancer.
AB  - Beta-glucans are widely used in treatment, cosmetics, and the food industry.
      Glucans play a significant role in activation of the immune and antioxidant
      system and inhibiting tumor proliferation. In the current study the antitumor
      activities of new high and low molecular weight beta-glucan derived from oats
      were investigated in two human lung cancer cell line (A549, H69AR) and normal
      keratinocytes (HaCaT). The effect of high and low molecular weight beta-glucan
      from oat was evaluated by cellular viability assessment, lipid peroxidation and
      manganese superoxide dismutase evaluation and cytoskeleton visualisation.
      Additionally the level of red blood cells hemolysis was performed. Our results
      indicate strong anti-tumor properties of new beta-glucan from oat and at the same
      time no toxicity for normal cells.

PMID- 28756507
TI  - Adhesive capsulitis of the shoulder: pain intensity and distribution.
AB  - PURPOSE: Papers regarding adhesive capsulitis (AC) of the shoulder focused on
      etiology, epidemiology, diagnosis, and treatment; until now, information on
      shoulder pain characteristics is still scarce. Our aim was to analyze pain
      intensity and distribution in patients with AC. METHODS: The study group was
      composed of 278 (133M-145F) consecutive patients with AC. After diagnosis,
      shoulder pain distribution was assessed through an upper limb pain map and pain
      intensity through a visual analog scale. Patients were distinguished on the basis
      of gender, age, time elapsed from onset of symptoms, and severity of functional
      limitation. Data were submitted to statistical analysis. RESULTS: Intensity of
      shoulder pain caused by AC was higher in females (p < 0.05); it did not vary with
      the side and between patient younger and older than 55 years. Patients whose pain
      arose from more than 3 months suffered a lower intensity of shoulder pain.
      Furthermore, pain intensity was higher in the most severe form of AC (active
      forward flexion < 60 degrees ) (p < 0.05). Pain was localized predominantly on
      the anterior aspect of the shoulder (dermatomes C5-C6) and rarely extended beyond
      the distal third of the arm. No differences were found in pain distribution
      between male and female, between patients with pain from less or more than 3
      months and between different levels of AC severity (p > 0.05). CONCLUSION:
      Shoulder pain due to AC may be influenced by gender and severity of functional
      limitation. AC pain distribution principally involves anterior aspect of the
      shoulder with downward extension of the arm until its distal third. LEVELS OF
      EVIDENCE: Level IV.

PMID- 28756508
TI  - Orthopedic resident's learning curve for arthroscopic subscapularis tendon
      repair: short-term clinical and radiographic outcomes.
AB  - BACKGROUND: Arthroscopic subscapularis (SSC) repair is a technically demanding
      procedure with a long learning curve. As effective completion of resident's
      practical experience remains controversial, a prospective clinical study was
      performed to assess the functional and anatomical outcomes of subscapularis (SSC)
      arthroscopic repair by orthopedic residents. The pathological anatomy of the
      tears, the surgical approach and the difficulties encountered at the beginning of
      the learning curve were reported. MATERIALS AND METHODS: Between June 2009 and
      June 2010, 30 patients with rotator cuff tear were preoperatively evaluated with
      clinical exam, Constant and UCLA scores. Surgery was performed under arthroscopy
      by a team of three orthopedic surgeons in training. A SSC tear, if present, was
      recorded and treated. The same clinical exam and functional scores were repeated
      at minimum 6 months of follow-up. Subscapularis strength recovery and tendon
      healing were investigated with arthromagnetic resonance imaging. RESULTS: A SSC
      tear was observed in 11 cases out of 30 and treated arthroscopically. The
      clinical scores improved in all patients: the average Constant score increased
      from 34 +/- 14 to 77 +/- 11 and the UCLA score from 11 +/- 5 to 29 +/- 3. The SSC
      tests were negative in all patients with the exception of one. Tendon healing was
      observed in 10 out of 11 cases. CONCLUSIONS: Arthroscopic SSC repair performed by
      educated residents is possible and leads to good clinical and anatomical results.
      Surgery duration progressively improved as the learning curve advanced. LEVEL OF
      EVIDENCE: Level 2.

PMID- 28756509
TI  - Glenohumeral and scapulohumeral kinematic analysis of patients with traumatic
      anterior instability wearing a shoulder brace: a prospective laboratory study.
AB  - PURPOSE: To assess the effectiveness of a novel glenohumeral joint immobilizer,
      the S2 Shoulder Stabilizer(r), by evaluating shoulder kinematics with a
      stereophotogrammetry system. METHODS: Participants in this prospective laboratory
      study were recruited from patients with anterior traumatic instability awaiting
      arthroscopic glenohumeral stabilization. Glenohumeral and scapulohumeral
      kinematic data (arm abduction-adduction and internal-external rotation, and
      scapular pronation-retraction and mediolateral rotation) were collected twice,
      without and with the brace, using a VICONTM motion capture system, and processed
      with MATLAB(r) software. RESULTS: The tests showed a significantly lower joint
      angle during abduction-adduction (p = 0.0022) and external rotation (p = 0.0076)
      and a significantly lower (p = 0.0022) mediolateral scapular rotation angle in
      the limbs wearing the immobilizer. Humeral head translation during abduction
      adduction and internal-external rotation was also lower in the patients wearing
      the brace. CONCLUSIONS: The immobilizer significantly limited joint excursion in
      all planes of movement except internal rotation. The narrower humeral head
      translation with respect to the trunk, measured in the tests with the brace,
      demonstrates that the immobilizer achieves the goal of preserving joint stability
      in the movements that are at risk of dislocation.

PMID- 28756511
TI  - Biology and the art of abstraction.

PMID- 28756510
TI  - Latarjet procedure: evolution of the bone block and correspondent clinical
      relevance-a clinical and radiological study.
AB  - PURPOSE: The purpose of this study was to correlate the bone block graft
      position, its dimension, its reabsorption and its integration with clinical
      outcome in patients operated on for recurrent anterior shoulder instability.
      METHODS: Twenty-four patients affected by recurrent anterior shoulder dislocation
      and operated on using the Latarjet procedure were enrolled in this study. At 6
      and 24 months, patients were evaluated with the following scales: ROWE, WOSI,
      Oxford instability score, UCLA, DASH and Constant score. Patients underwent two
      postoperative CT scans: immediately after surgery (T0) and at 24 months post-op
      (T1). RESULTS: At 24 months, none of the 24 patients reported further episodes of
      dislocation. Clinically at the final follow-up, we found excellent results in all
      the evaluation scales. Mean reduction in bone graft from T0 to T1 was 42% of the
      overall volume; similarly reduction in the overall surface was 29.3%; decrease in
      length, width and depth was, respectively, 3.4, 2.2 and 1.0 mm; all these
      parameters decreased significantly (p < 0.05). No correlations were found between
      radiological parameters and clinical and functional outcomes. CONCLUSIONS: The
      results confirm that a lack of integration or a significant reabsorption of the
      graft is present in the Latarjet procedure, but they do not significantly affect
      the clinical and functional results.

PMID- 28756512
TI  - Modelling, inference and big data in biophysics.
AB  - In recognition of the increasing importance of big data in biophysics, a new
      session called 'Modelling, inference, big data' is incorporated into the
      IUPAB/EBSA Congress on 18 July 2017 at Edinburgh, UK.

PMID- 28756513
TI  - The natural history of perforated foregut ulcers after repair by omental patching
      or primary closure.
AB  - BACKGROUND: The treatment of perforated foregut ulcers by omental patching (OP)
      or primary closure has mostly replaced vagotomy and pyloroplasty/antrectomy
      (VPA). We sought to determine the natural history and recurrence rate of
      ulceration in patients treated by omental patching or primary closure. STUDY
      DESIGN: An 11-year retrospective study. RESULTS: From 2004 through 2015, 94
      patients had perforated foregut ulcers, 53 gastric, and 41 duodenal. 77 (82%)
      were treated by OP alone (study group) and 17 (18%) were treated with VPA
      (comparison group). All OP patients were discharged on PPIs, but only 86% took
      the drugs for a median of 22 months (1-192, SD 40). Endoscopy in the OP group
      showed recurrent ulcers in nine (12% recurrence rate) and gastritis in three (4%)
      This group also had three later recurrent perforations. Another recurrent ulcer
      hemorrhaged causing death (3% late mortality). Two other patients required non
      emergent re-do ulcer operations for recurrent disease/symptoms (surgical re
      intervention rate 4%). Total length of follow-up was median 44 months (1-192, SD
      40) and was complete in 82 (87%). 18 (23%) patients in the OP group developed
      recurrent abdominal pain attributed to ulcer disease during follow-up, compared
      to 2 (12%) in the VPA group (p = 0.15). No patient in the VPA group had an
      endoscopic recurrence or re-intervention. CONCLUSION: Omental patching does not
      correct the underlying disease process which causes foregut perforation, and has
      a 12% endoscopically proven recurrent ulceration rate and a 23% incidence of
      recurrent symptoms within 44 months. Patients tend to stop taking PPIs after 22
      months at which time their risk increases.

PMID- 28756515
TI  - Reconstruction of chromosome rearrangements between the two most ancestral
      duckweed species Spirodela polyrhiza and S. intermedia.
AB  - The monophyletic duckweeds comprising five genera within the monocot order
      Alismatales are neotenic, free-floating, aquatic organisms with fast vegetative
      propagation. Some species are considered for efficient biomass production, for
      life stock feeding, and for (simultaneous) wastewater phytoremediation. The
      ancestral genus Spirodela consists of only two species, Spirodela polyrhiza and
      Spirodela intermedia, both with a similar small genome (~160 Mbp/1C). Reference
      genome drafts and a physical map of 96 BACs on the 20 chromosome pairs of S.
      polyrhiza strain 7498 are available and provide useful tools for further
      evolutionary studies within and between duckweed genera. Here we applied
      sequential comparative multicolor fluorescence in situ hybridization (mcFISH) to
      address homeologous chromosomes in S. intermedia (2n = 36), to detect chromosome
      rearrangements between both species and to elucidate the mechanisms which may
      have led to the chromosome number alteration after their evolutionary separation.
      Ten chromosome pairs proved to be conserved between S. polyrhiza and S.
      intermedia, the remaining ones experienced, depending on the assumed direction of
      evolution, translocations, inversion, and fissions, respectively. These results
      represent a first step to unravel karyotype evolution among duckweeds and are
      anchor points for future genome assembly of S. intermedia.

PMID- 28756514
TI  - Visuomotor and motorvisual priming with different types of set-level congruency:
      evidence in support of ideomotor theory, and the planning and control model
      (PCM).
AB  - Perception can prime action (visuomotor priming), and action can prime perception
      (motorvisual priming). According to ideomotor theory both effects rely on the
      overlap of mental representations between perception and action. This implies
      that both effects get more pronounced the more features they share. We tested
      this hypothesis by employing in a motorvisual (Exp. 1) and in a visuomotor (Exp.
      2) setting, three different pairs of left/right target stimuli (hand pictures,
      arrows, and words) varying in how strongly they overlap with the pair of
      left/right responses. For two stimulus pairs (hands and words) the hypothesis was
      confirmed: hand pictures share more features with the responses than words,
      consequently hand pictures produced a stronger visuomotor and a stronger
      motorvisual priming effect than words. However, arrow stimuli showed a different
      pattern: the temporal dynamics of both priming effects, as well as the direction
      of the effect seen in motorvisual priming, were significant but opposite to that
      of the hand and word stimuli. This suggests that the arrows' representations were
      not involved in ideomotor processes, and we propose instead that they were
      represented in a spatial or scalar fashion, outside the representations assumed
      in ideomotor theory. The results are discussed in the context of ideomotor
      theory, and the planning and control model of motorvisual priming.

PMID- 28756517
TI  - Urogynaecology providers' attitudes towards postnatal pelvic floor dysfunction.
AB  - INTRODUCTION AND HYPOTHESIS: Postnatal pelvic floor dysfunction (PFD) has a high
      prevalence and morbidity amongst parturient women. Women should be counselled
      regarding postnatal PFD. Our aim was to determine urogynaecology providers'
      knowledge of risk and protective factors for postnatal PFD, and to assess their
      practice patterns in postnatal PFD counselling. METHODS: An electronic survey was
      distributed to members of the European Urogynaecology Association (EUGA) and
      International Urogynaecology Association (IUGA). Data were collected on
      urogynaecology providers' demographics, awareness of pregnancy-related PFD risk
      and protective factors, beliefs surrounding PFD risk-estimate tools, practice
      patterns in PFD counselling, and personal or spousal preferences for using
      caesarean section (CS) as a means of postnatal PFD prevention. RESULTS: Overall,
      372 healthcare providers responded to the survey, 84 from the EUGA and 288 from
      the IUGA. Most reported practicing as a urogynaecologist (67%) and or
      obstetrician (44%). An overwhelming majority of respondents were aware of the
      major risk and protective factors for PFD, and almost 60% believed that risk
      estimate tools for PFD could be clinically useful. Many denied enquiring about
      symptoms of PFD prenatally and postnatally (33% and 25% respectively), and
      reported not routinely counselling on prevention of postnatal PFD (39%). Nearly
      25% reported that they would prefer CS for themselves or their spouse for
      prevention of postnatal PFD. CONCLUSION: Urogynaecology providers are aware of
      risk and protective factors for postnatal PFD, but many fail to educate patients
      on the topic. The development of an easy-use risk-estimate tool for postnatal PFD
      could improve counselling rates in the future.

PMID- 28756516
TI  - Synthetic lethality in malignant pleural mesothelioma with PARP1 inhibition.
AB  - Malignant pleural mesotheliomas (MPM) are most often surgically unresectable, and
      they respond poorly to current chemotherapy and radiation therapy. Between 23 and
      64% of malignant pleural mesothelioma have somatic inactivating mutations in the
      BAP1 gene. BAP1 is a homologous recombination (HR) DNA repair component found in
      the BRCA1/BARD1 complex. Similar to BRCA1/2 deficient cancers, mutation in the
      BAP1 gene leads to a deficient HR pathway and increases the reliance on other DNA
      repair pathways. We hypothesized that BAP1-mutant MPM would require PARP1 for
      survival, similar to the BRCA1/2 mutant breast and ovarian cancers. Therefore, we
      used the clinical PARP1 inhibitors niraparib and olaparib to assess whether they
      could induce synthetic lethality in MPM. Surprisingly, we found that all MPM cell
      lines examined, regardless of BAP1 status, were addicted to PARP1-mediated DNA
      repair for survival. We found that niraparib and olaparib exposure markedly
      decreased clonal survival in multiple MPM cell lines, with and without BAP1
      mutations. This clonal cell death may be due to the extensive replication fork
      collapse and genomic instability that PARP1 inhibition induces in MPM cells. The
      requirement of MPM cells for PARP1 suggests that they may generally arise from
      defects in HR DNA repair. More importantly, these data demonstrate that the PARP1
      inhibitors could be effective in the treatment of MPM, for which little effective
      therapy exists.

PMID- 28756518
TI  - Ethics, Evidence Based Sports Medicine, and the Use of Platelet Rich Plasma in
      the English Premier League.
AB  - The use of platelet rich plasma (PRP) as a novel treatment is discussed in the
      context of a qualitative research study comprising 38 interviews with sports
      medicine practitioners and other stakeholders working within the English Premier
      League during the 2013-16 seasons. Analysis of the data produced several
      overarching themes: conservatism versus experimentalism in medical attitudes;
      therapy perspectives divergence; conflicting versions of appropriate evidence;
      subcultures; community beliefs/practices; and negotiation of medical decision
      making. The contested evidence base for the efficacy of PRP is presented in the
      context of a broader professional shift towards evidence based medicine within
      sports medicine. Many of the participants while accepting this shift are still
      committed to casuistic practices where clinical judgment is flexible and does not
      recognize a context-free hierarchy of evidentiary standards to ethically
      justifiable practice. We also discuss a tendency in the data collected to
      consider the use of deceptive, placebo-like, practices among the clinician
      participants that challenge dominant understandings of informed consent in
      medical ethics. We conclude that the complex relation between evidence and ethics
      requires greater critical scrutiny for this emerging specialism within the
      medical community.

PMID- 28756519
TI  - Anti-Inflammatory Effects of Licochalcone A on IL-1beta-Stimulated Human
      Osteoarthritis Chondrocytes.
AB  - Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra),
      has been reported to have anti-inflammatory activity. In this study, we evaluated
      the anti-inflammatory effects of Lico A on IL-1beta-stimulated human
      osteoarthritis chondrocytes and investigated the possible mechanism. Results
      demonstrated that Lico A treatment significantly inhibited PGE2 and NO production
      induced by IL-1beta. IL-1beta-induced iNOS and COX-2 expression were also
      inhibited by Lico A. Lico A inhibited MMP1, MMP3, and MMP13 production in IL
      1beta-stimulated chondrocytes. Lico A also inhibited IL-1beta-induced
      phosphorylation of NF-kappaB p65 and IkappaBalpha. Meanwhile, Lico A was found to
      upregulate the expression of Nrf2 and HO-1. However, Nrf2 siRNA reversed the anti
      inflammatory effects of Lico A. In conclusion, our results suggested that Lico A
      showed anti-inflammatory effects in IL-1beta-stimulated chondrocytes by
      activating Nrf2 signaling pathway.

PMID- 28756520
TI  - Cyclophilin A Aggravates Collagen-Induced Arthritis via Promoting Classically
      Activated Macrophages.
AB  - Activated macrophages exhibiting diverse phenotypes and various functions
      contribute to the pathogenesis or amelioration of different diseases like cancer,
      inflammation, and infectious and autoimmune diseases. However, the mechanisms of
      macrophage polarization in inflamed joint and its effects on rheumatoid arthritis
      (RA) are still not clarified. This study is designed to explore the effects of
      cyclophilin A (CypA) on macrophage polarization and describe the underlying
      mechanisms. Collagen-induced arthritis (CIA) was employed to address the pro
      arthritic effects of CypA. Flow cytometry was performed to investigate the
      populations of M1 and M2 macrophages in synovial tissues of the mice. Knockdown
      or overexpression of CypA macrophage cells was used to study the functions of
      CypA on macrophage polarization. Western blot was carried out to examine the
      potential signaling pathways. We found that CypA aggravated the severity of CIA
      in mice, as assessed by the increase of clinical score of inflammation, cartilage
      damage, and bone erosion. Moreover, the level of cytokines, such as IL-6, IL
      1beta, and IL-17, and the number of pro-inflammatory macrophages in synovial
      fluid were significantly elevated. In accordance with our observation, CypA
      dysregulation could actually influence the M1 macrophages polarization and pro
      inflammatory cytokines production. Further mechanism study disclosed that CypA
      could regulate the transcriptional activity of NF-kappaB, the pivotal
      transcriptional factor regulating M1 polarization, dependent of its PPIase
      activity. Our findings provide evidence that PPIase CypA promoted macrophages
      polarization toward pro-inflammatory M1 phenotype via transcriptional activating
      NF-kappaB, thus leading to aggravated arthritis.

PMID- 28756521
TI  - Increased risk for hypothyroidism after anticholinesterase pesticide poisoning: a
      nationwide population-based study.
AB  - PURPOSE: Previous animal studies have reported that acute anticholinesterase
      pesticide (organophosphate and carbamate) poisoning may affect thyroid hormones.
      However, there is no human study investigating the association between
      hypothyroidism and anticholinesterase pesticide poisoning, and therefore, we
      conducted a retrospective nationwide population-based cohort study to delineate
      this issue. METHODS: We identified 10,372 anticholinesterase pesticide poisoning
      subjects and matched 31,116 non-anticholinesterase pesticide poisoning subjects
      between 2003 and 2012 from the Nationwide Poisoning Database and the Longitudinal
      Health Insurance Database 2000, respectively, in a 1:3 ratio by index date, age,
      and sex for this study. We compared the cumulative incidence of hypothyroidism
      between the two cohorts by following up until 2013. Independent predictors for
      hypothyroidism were also investigated. RESULTS: In total, 75 (0.72%)
      anticholinesterase pesticide poisoning subjects and 184 (0.59%) non
      anticholinesterase pesticide poisoning subjects were diagnosed with
      hypothyroidism during the follow-up. Cox proportional hazard regression analysis
      showed that anticholinesterase pesticide poisoning subjects had higher risk for
      hypothyroidism than did non-anticholinesterase pesticide poisoning subjects
      (adjusted hazard ratio: 1.47, 95% confidence interval: 1.11-1.95) after adjusting
      for age, sex, hypertension, malignancy, liver disease, renal disease, atrial
      fibrillation or flutter, thyroiditis, goiter, other endocrine disorders, and
      mental disorder. Stratified analysis showed that anticholinesterase pesticide
      poisoning subjects had higher risk for hypothyroidism than did non
      anticholinesterase pesticide poisoning subjects in terms of the age subgroup of
      40-64 years, female sex, past history of goiter, follow-up of <1 month, and
      anticholinesterase pesticide poisoning subjects without atropine treatment
      (incidence rate ratio [IRR]: 1.66, 95% confidence interval: 1.20-2.30). Female
      sex, malignancy, renal disease, thyroiditis, goiter, mental disorder, and
      anticholinesterase pesticide poisoning without atropine treatment were
      independent predictors for hypothyroidism. CONCLUSIONS: Anticholinesterase
      pesticide poisoning is associated with increased risk for hypothyroidism. Early
      evaluation of thyroid function in anticholinesterase pesticide poisoning subjects
      is suggested, especially in subjects without atropine treatment, aged 40-64
      years, female sex, and past history of goiter.

PMID- 28756522
TI  - Defining fitness in an uncertain world.
AB  - The recently elucidated definition of fitness employed by Fisher in his
      fundamental theorem of natural selection is combined with reproductive values as
      appropriately defined in the context of both random environments and continuing
      fluctuations in the distribution over classes in a class-structured population.
      We obtain astonishingly simple results, generalisations of the Price Equation and
      the fundamental theorem, that show natural selection acting only through the
      arithmetic expectation of fitness over all uncertainties, in contrast to previous
      studies with fluctuating demography, in which natural selection looks rather
      complicated. Furthermore, our setting permits each class to have its
      characteristic ploidy, thus covering haploidy, diploidy and haplodiploidy at the
      same time; and allows arbitrary classes, including continuous variables such as
      condition. The simplicity is achieved by focussing just on the effects of natural
      selection on genotype frequencies: while other causes are present in the model,
      and the effect of natural selection is assessed in their presence, these causes
      will have their own further effects on genoytpe frequencies that are not assessed
      here. Also, Fisher's uses of reproductive value are shown to have two
      ambivalences, and a new axiomatic foundation for reproductive value is endorsed.
      The results continue the formal darwinism project, and extend support for the
      individual-as-maximising-agent analogy to finite populations with random
      environments and fluctuating class-distributions. The model may also lead to
      improved ways to measure fitness in real populations.

PMID- 28756523
TI  - The combinatorics of discrete time-trees: theory and open problems.
AB  - A time-tree is a rooted phylogenetic tree such that all internal nodes are
      equipped with absolute divergence dates and all leaf nodes are equipped with
      sampling dates. Such time-trees have become a central object of study in
      phylogenetics but little is known about the parameter space of such objects. Here
      we introduce and study a hierarchy of discrete approximations of the space of
      time-trees from the graph-theoretic and algorithmic point of view. One of the
      basic and widely used phylogenetic graphs, the [Formula: see text] graph, is the
      roughest approximation and bottom level of our hierarchy. More refined
      approximations discretize the relative timing of evolutionary divergence and
      sampling dates. We study basic graph-theoretic questions for these graphs,
      including the size of neighborhoods, diameter upper and lower bounds, and the
      problem of finding shortest paths. We settle many of these questions by extending
      the concept of graph grammars introduced by Sleator, Tarjan, and Thurston to our
      graphs. Although time values greatly increase the number of possible trees, we
      show that 1-neighborhood sizes remain linear, allowing for efficient local
      exploration and construction of these graphs. We also obtain upper bounds on the
      r-neighborhood sizes of these graphs, including a smaller bound than was
      previously known for [Formula: see text]. Our results open up a number of
      possible directions for theoretical investigation of graph-theoretic and
      algorithmic properties of the time-tree graphs. We discuss the directions that
      are most valuable for phylogenetic applications and give a list of prominent open
      problems for those applications. In particular, we conjecture that the split
      theorem applies to shortest paths in time-tree graphs, a property not shared in
      the general [Formula: see text] case.

PMID- 28756524
TI  - Muscle satellite cells are functionally impaired in myasthenia gravis:
      consequences on muscle regeneration.
AB  - Myasthenia gravis (MG) is a neuromuscular disease caused in most cases by anti
      acetyl-choline receptor (AChR) autoantibodies that impair neuromuscular signal
      transmission and affect skeletal muscle homeostasis. Myogenesis is carried out by
      muscle stem cells called satellite cells (SCs). However, myogenesis in MG had
      never been explored. The aim of this study was to characterise the functional
      properties of myasthenic SCs as well as their abilities in muscle regeneration.
      SCs were isolated from muscle biopsies of MG patients and age-matched controls.
      We first showed that the number of Pax7+ SCs was increased in muscle sections
      from MG and its experimental autoimmune myasthenia gravis (EAMG) mouse model.
      Myoblasts isolated from MG muscles proliferate and differentiate more actively
      than myoblasts from control muscles. MyoD and MyoG were expressed at a higher
      level in MG myoblasts as well as in MG muscle biopsies compared to controls. We
      found that treatment of control myoblasts with MG sera or monoclonal anti-AChR
      antibodies increased the differentiation and MyoG mRNA expression compared to
      control sera. To investigate the functional ability of SCs from MG muscle to
      regenerate, we induced muscle regeneration using acute cardiotoxin injury in the
      EAMG mouse model. We observed a delay in maturation evidenced by a decrease in
      fibre size and MyoG mRNA expression as well as an increase in fibre number and
      embryonic myosin heavy-chain mRNA expression. These findings demonstrate for the
      first time the altered function of SCs from MG compared to control muscles. These
      alterations could be due to the anti-AChR antibodies via the modulation of
      myogenic markers resulting in muscle regeneration impairment. In conclusion, the
      autoimmune attack in MG appears to have unsuspected pathogenic effects on SCs and
      muscle regeneration, with potential consequences on myogenic signalling pathways,
      and subsequently on clinical outcome, especially in the case of muscle stress.

PMID- 28756525
TI  - Non-operative Care of the Patient with an ACL-Deficient Knee.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update to the most
      objective, evidence-based path through a non-operative course of rehabilitation
      after anterior cruciate ligament injury for those hoping to return to pivoting
      and cutting sports. RECENT FINDINGS: Anterior cruciate ligament (ACL) injuries
      are prevalent in pivoting and cutting athletes with many of these patients
      electing to pursue surgical reconstruction in hopes of returning to prior levels
      of function. Despite many athletes pursing ACL reconstruction, some may elect to
      pursue a non-operative course of care. Success with this treatment plan should be
      defined as the ability to return to sport without subsequent giving way episodes.
      Identification of those most likely to successfully return to sport with a non
      operative course begins with completion of an evidence-based screening tool. If
      the patient has no concomitant injury and successfully passes the screening, they
      may proceed to a systematic, evidence-based progression through rehabilitation.
      Finally, the patient must complete a return to sport program and meet appropriate
      objective criteria, prior to return to sport.

PMID- 28756526
TI  - Novel use of porcine extracellular matrix in recurrent stricture following repair
      of tracheoesophageal fistula.
AB  - Anastomotic stricture is a common complication following repair of esophageal
      atresia (EA). Many factors are thought to contribute to stricture formation and a
      variety of management techniques have been developed. In this case report, we
      describe the treatment of a recurrent anastomotic stricture following repair of
      long-gap esophageal atresia. Porcine bladder extracellular matrix (ECM) was
      mounted on a stent and delivered endoscopically to the site of recurrent
      stricture. An appropriate positioning was confirmed using direct endoscopic
      visualization and intra-operative fluoroscopy. The patient recovered well with
      persistent radiographic and functional improvements in previous stricture.

PMID- 28756527
TI  - Synergistic tumor suppression by a Perilla frutescens-derived methoxyflavanone
      and anti-cancer tyrosine kinase inhibitors in A549 human lung adenocarcinoma.
AB  - Anti-cancer tyrosine kinase inhibitors (TKIs) are effective in many types of
      cancers including non-small cell lung cancer, while appearance of TKI-resistant
      tumors suggests a need for the development of their potentiation strategies. We
      have previously shown that a methoxyflavanone derivative from the Asian medicinal
      herb Perilla frutescens (Perilla-derived methoxyflavanone; PDMF) shows a
      prominent anti-tumor activity against A549 human lung adenocarcinoma. Here we
      show that PDMF and anti-cancer TKIs (nilotinib, bosutinib, dasatinib, and
      ponatinib) synergistically suppress proliferation of A549 cells. Flow cytometric
      analysis indicated that co-stimulation with nilotinib (4 MUM) and PDMF induced
      G2/M cell cycle arrest in low PDMF doses (10-50 MUM), whereas this combination
      triggered de novo G1 arrest in higher PDMF dosages (50-125 MUM). We also found
      that co-administration with nilotinib and PDMF significantly suppressed in vivo
      tumorigenicity of A549 cells in athymic nude mice.

PMID- 28756528
TI  - Changes in incontinence after hysterectomy.
AB  - PURPOSE: Information about the perioperative incontinence following hysterectomy
      is limited. To advance the postoperative rehabilitation further we need more
      information about qualitative changes in incontinence, fatigue and physical
      function of patients undergoing hysterectomy. METHODS: 108 patients undergoing
      planned hysterectomy were compared pre- and postoperatively. In a sub-study of
      the prospective follow-up study the changes in incontinence, postoperative
      fatigue, quality of life, physical function, and body composition were evaluated
      preoperatively, 13 and 30 days postoperatively. Sample size calculation indicated
      that 102 women had to be included. The incontinence status was estimated by a
      Danish version of the ICIG questionnaire; further, visual analogue scale,
      dynamometer for hand grip, knee extension strength and balance were applied. Work
      capacity was measured ergometer cycle together with lean body mass by impedance.
      Quality of life was assessed using the SF-36 questionnaire. Patients were
      examined preoperatively and twice postoperatively. RESULTS: In total 41 women
      improved their incontinence after hysterectomy and 10 women reported
      deterioration. Preoperative stress incontinence correlated with BMI (r = 0.25, p
      < 0.01) and urge incontinence with age (r = 0.24, p < 0.02). Further, improvement
      after hysterectomy in stress incontinence was associated with younger age (r =
      0.20, p < 0.04). Improvement in urge incontinence was positively associated with
      BMI (r = 0.22, p = 0.02). A slight but significant loss was seen in lean body
      mass 13 and 30 days postoperatively. CONCLUSIONS: Hysterectomy was not
      significantly associated with the risk of incontinence; in particular, when no
      further vaginal surgery is performed. Hysterectomy may even have a slightly
      positive effect on incontinence and de-novo cure.

PMID- 28756529
TI  - Risk of preterm birth and low birthweight following consecutive surgical and
      medical abortions.
AB  - PURPOSE: To examine the effect of consecutive surgical compared to medical
      uterine evacuations on spontaneous preterm birth (SPTB) and low birthweight (LBW)
      rates in the immediate subsequent delivery. METHODS: Retrospective study,
      conducted at a teaching hospital on data from January 2000 to March 2016. First
      study group consisted of all women who had >=2 consecutive medical evacuations
      (ME-Group); second study group consisted of women who had >=2 consecutive
      surgical evacuations (SE-Group). Both had a subsequent singleton delivery.
      Control group consisted of women without previous evacuations (unexposed group).
      The groups were matched for year of birth and ethnicity. The primary outcome was
      a composite that included SPTB (<37 weeks) and LBW (<2500 g). RESULTS: All 70
      women found eligible in the ME-Group during the study period were included. SE
      Group and the unexposed group consisted of 140 and 210 women, respectively.
      Primary outcome occurred in 4.3, 11.4, and 2.4% in the ME-Group, SE-Group, and
      the unexposed group, respectively (p = 0.002). After adjusting for variables that
      differed between the groups in univariate analysis, the primary outcome incidence
      was significantly higher among the SE-Group compared to the unexposed group
      (adjusted OR 6.8, 95% CI 1.7-26.3, p = 0.006). The difference was insignificant
      between the ME-Group and the unexposed group (adjusted p = 0.31). In the SE
      Group, 7.1% women required fertility treatments to achieve a desired pregnancy
      compared to 1.4% in the ME-Group (p = 0.04). CONCLUSION: Two or more consecutive
      surgical evacuations were associated with an increased risk of both SPTB and LBW
      compared to unexposed group.

PMID- 28756530
TI  - Intricatinol synergistically enhances the anticancerous activity of cisplatin in
      human A549 cells via p38 MAPK/p53 signalling.
AB  - Platinum containing drugs are widely used to treat advanced lung carcinomas.
      However, their clinical success is still limited due to severe side effects, and
      drug resistance. Alternative approaches are warranted to augment efficacy of
      platinum based chemotherapeutic drugs with minimal side effects. Intricatinol
      (INT), a homoisoflavonoid, has been shown to possess anti-tubercular,
      antioxidant, hypoglycaemic, and hypolipidemic activity. However, its anticancer
      activity largely remains unknown. In the present study, we have evaluated
      anticancer potential of INT alone or in combination with cisplatin (CIS) in non
      small cell lung carcinoma (A549) cells. Treatment with INT alone reduced the
      viability of A549 cells in a dose-dependent manner. Interestingly, the
      combination of low doses of INT and CIS exerted a synergistic effect and induced
      apoptosis as evident by DNA fragmentation and Annexin V positive cells. Enhanced
      Bax:Bcl-2 ratio, loss of Deltapsim, cytochrome c release, cleavage of caspase 3
      and PARP1 strongly corroborated our findings. Further, increased expression of
      p53, p38 MAPK and their phosphorylated counterparts, loss of clonogenicity and
      reduced migration potential were also recorded with INT + CIS treatment. Most
      interestingly, INT could not induce any significant cell death in primary mouse
      embryonic fibroblasts (MEFs). Moreover, no additive or synergistic effect was
      noted with INT + CIS in MEFs under similar treatment conditions. In conclusion,
      INT has a selective anticancer potential and could synergize cytotoxicity of CIS.
      Therefore, the combination of INT and CIS may serve as an effective anticancer
      strategy for the treatment of non-small cell lung carcinoma.

PMID- 28756532
TI  - Etanercept is effective as monotherapy or in combination with methotrexate in
      rheumatoid arthritis: subanalysis of an observational study.
AB  - Approximately 30% of patients with rheumatoid arthritis receiving biological
      disease-modifying antirheumatic drugs (bDMARDs) take them as monotherapy.
      Although etanercept (ETN) monotherapy has been evaluated in clinical trials, data
      in the real-world setting are sparse. We compared the efficacy and safety of ETN,
      given alone or in combination with methotrexate (MTX), in routine clinical
      practice. This was a subanalysis of patients who received either ETN alone or ETN
      + MTX during a 52-week prospective, observational study conducted at 329 German
      centers. The primary endpoint was "Funktionsfragebogen Hannover" (Hannover
      Functional Ability Questionnaire [FFbH]; low FFbH = worse function) functional
      remission at week 26 and week 52. Secondary endpoints included the 28-joint count
      Disease Activity Score (DAS28), DAS28 remission (DAS28 < 2.6), and adverse events
      (AEs). Participating centers applied ETN monotherapy in 43.1% of patients and ETN
      + MTX in 56.9%. A smaller proportion of patients achieved FFbH functional
      remission with ETN vs ETN + MTX (31.9%, 95% confidence interval [CI] 29.1-34.9%
      vs 39.8%, 37.2-42.5%, respectively; p < 0.001) at 26 weeks and at 52 weeks
      (38.4%, 35.1-41.7% vs 44.3%, 41.5-47.2%, respectively; p = 0.007). After 52
      weeks, the mean DAS28 (+/-SD) decreased from 5.5 +/- 1.3 to 3.4 +/- 1.4 (ETN) vs
      5.3 +/- 1.3 to 3.2 +/- 1.3 (ETN + MTX) and DAS28 remission was achieved by 32.5%
      (95% CI 29.0-36.1%) of patients with ETN vs 38.8% (35.8-41.9%; p = 0.007) with
      ETN + MTX. Overall, 20.6 (ETN) and 19.7% (ETN + MTX) of patients reported
      treatment-related AEs. Patients received ETN monotherapy almost as often as ETN +
      MTX. ETN + MTX appeared marginally more effective than ETN monotherapy in some,
      but not all, outcomes measured.

PMID- 28756531
TI  - Dysphagia in the Elderly.
AB  - OPINION STATEMENT: Dysphagia is a common problem in the elderly population with
      an especially high prevalence in hospitalized and institutionalized patients. If
      inadequately addressed, dysphagia leads to significant morbidity and contributes
      to decreased quality of life. Dysphagia can be categorized as emanating from
      either an oropharyngeal or esophageal process. A disproportionate number of
      elderly patients suffer from oropharyngeal dysphagia with a multifactorial
      etiology. Historically, treatment options have been limited and included mostly
      supportive care with a focus on dietary modification, food avoidance, and swallow
      rehabilitation. Nascent technologies such as the functional luminal imaging probe
      (FLIP) and advances in esophageal manometry are improving our understanding of
      the pathophysiology of oropharyngeal dysphagia. Recent developments in the
      treatment of specific causes of oropharyngeal dysphagia, including endoscopic
      balloon dilations for upper esophageal sphincter (UES) dysfunction, show promise
      and are expected to enhance with further research. Esophageal dysphagia is also
      common in the elderly and more commonly due to an identifiable cause. The full
      breadth of treatment options is frequently unavailable to elderly patients due to
      comorbidities and overall functional status. However, the increasing availability
      of less invasive solutions to specific esophageal pathologies has augmented the
      number of treatment options available to this population, where an individualized
      approach to patient care is paramount. This review focuses on the evaluation and
      management of dysphagia in the elderly and delineates how standard and novel
      therapeutics are contributing to more nuanced and personalized management.

PMID- 28756534
TI  - Statistical science: a grammar for research.
AB  - I greatly appreciate the invitation to give this lecture with its century long
      history. The title is a warning that the lecture is rather discursive and not
      highly focused and technical. The theme is simple. That statistical thinking
      provides a unifying set of general ideas and specific methods relevant whenever
      appreciable natural variation is present. To be most fruitful these ideas should
      merge seamlessly with subject-matter considerations. By contrast, there is
      sometimes a temptation to regard formal statistical analysis as a ritual to be
      added after the serious work has been done, a ritual to satisfy convention,
      referees, and regulatory agencies. I want implicitly to refute that idea.

PMID- 28756533
TI  - Long-term spironolactone treatment reduces coronary TRPC expression,
      vasoconstriction, and atherosclerosis in metabolic syndrome pigs.
AB  - Coronary transient receptor potential canonical (TRPC) channel expression is
      elevated in metabolic syndrome (MetS). However, differential contribution of
      TRPCs to coronary pathology in MetS is not fully elucidated. We investigated the
      roles of TRPC1 and TRPC6 isoforms in coronary arteries of MetS pigs and
      determined whether long-term treatment with a mineralocorticoid receptor
      inhibitor, spironolactone, attenuates coronary TRPC expression and associated
      dysfunctions. MetS coronary arteries exhibited significant atherosclerosis,
      endothelial dysfunction, and increased histamine-induced contractions.
      Immunohistochemical studies revealed that TRPC6 immunostaining was significantly
      greater in the medial layer of MetS pig coronary arteries compared to that in
      Lean pigs, whereas little TRPC6 immunostaining was found in atheromas.
      Conversely, TRPC1 immunostaining was weak in the medial layer but strong in MetS
      atheromas, where it was predominantly localized to macrophages. Spironolactone
      treatment significantly decreased coronary TRPC expression and dysfunctions in
      MetS pigs. In vivo targeted delivery of the dominant-negative (DN)-TRPC6 cDNA to
      the coronary wall reduced histamine-induced calcium transients in the MetS
      coronary artery medial layer, implying a role for TRPC6 in mediating calcium
      influx in MetS coronary smooth muscles. Monocyte adhesion was increased in Lean
      pig coronary arteries cultured in the presence of aldosterone; and spironolactone
      antagonized this effect, suggesting that coronary mineralocorticoid receptor
      activation may regulate macrophage infiltration. TRPC1 expression in atheroma
      macrophages was associated with advanced atherosclerosis, whereas medial TRPC6
      upregulation correlated with increased histamine-induced calcium transients and
      coronary contractility. We propose that long-term spironolactone treatment may be
      a therapeutic strategy to decrease TRPC expression and coronary pathology
      associated with MetS.

PMID- 28756536
TI  - Therapeutic blockade of Foxp3 in experimental breast cancer models.
AB  - PURPOSE: Regulatory T cells (Tregs) impair the clinical benefit of cancer
      immunotherapy. To optimize the antitumor efficacy of therapeutic dendritic cell
      (DC) vaccines, we aimed to inhibit Foxp3, a transcription factor required for
      Treg function. METHODS: Mice bearing established syngeneic LM3 and 4T1 breast
      tumors were treated with antitumor DC vaccines and a synthetic peptide (P60) that
      has been shown to inhibit Foxp3. RESULTS: Treatment with P60 improved the
      therapeutic efficacy of DC vaccines in these experimental models. In addition,
      monotherapy with P60 inhibited tumor growth in immunocompetent as well as in
      immuno-compromised animals bearing established tumors. We found expression of
      Foxp3 in human and murine breast tumor cells. P60 inhibited IL-10 secretion in
      breast cancer cells that expressed Foxp3. CONCLUSIONS: Our results suggest that
      Foxp3 blockade improves the therapeutic efficacy of DC vaccines by inhibition of
      Tregs and through a direct antitumor effect. This strategy could prove useful to
      neutralize the immunosuppressive microenvironment and to boost antitumor immunity
      in breast cancer.

PMID- 28756535
TI  - FOXA1 hypermethylation: link between parity and ER-negative breast cancer in
      African American women?
AB  - BACKGROUND: Reproductive factors, particularly parity, have differential effects
      on breast cancer risk according to estrogen receptor (ER) status, especially
      among African American (AA) women. One mechanism could be through DNA
      methylation, leading to altered expression levels of genes important in cell fate
      decisions. METHODS: Using the Illumina 450K BeadChip, we compared DNA methylation
      levels in paraffin-archived tumor samples from 383 AA and 350 European American
      (EA) women in the Women's Circle of Health Study (WCHS). We combined 450K
      profiles with RNA-seq data and prioritized genes based on differential
      methylation by race, correlation between methylation and gene expression, and
      biological function. We measured tumor protein expression and assessed its
      relationship to DNA methylation. We evaluated associations between reproductive
      characteristics and DNA methylation using linear regression. RESULTS: 410 loci
      were differentially methylated by race, with the majority unique to ER- tumors.
      FOXA1 was hypermethylated in tumors from AA versus EA women with ER- cancer, and
      increased DNA methylation correlated with reduced RNA and protein expression.
      Importantly, parity was positively associated with FOXA1 methylation among AA
      women with ER- tumors (P = 0.022), as was number of births (P = 0.026),
      particularly among those who did not breastfeed (P = 0.008). These same
      relationships were not observed among EA women, although statistical power was
      more limited. CONCLUSIONS: Methylation and expression of FOXA1 is likely impacted
      by parity and breastfeeding. Because FOXA1 regulates a luminal gene expression
      signature in progenitor cells and represses the basal phenotype, this could be a
      mechanism that links these reproductive exposures with ER- breast cancer.

PMID- 28756537
TI  - Atypical Morphology and Disparate Speciation in a Case of Feline Cryptococcosis.
AB  - A 6-year-old, spayed female cat was presented with acute respiratory signs and
      pleural effusion. Computed tomography scan revealed a large, lobulated mass
      effect in the ventral right hemithorax with concurrent sternal lymphadenopathy. A
      cytologic sample of the mass contained pyogranulomatous inflammation, necrotic
      material, and abundant yeast structures that lacked a distinct capsule and
      demonstrated rare pseudohyphal forms. Fungal culture and biochemical testing
      identified the yeast as Cryptococcus albidus, with susceptibility to all
      antifungal agents tested. However, subsequent 18S PCR identified 99% homology
      with a strain of Cryptococcus neoformans and only 92% homology with C. albidus.
      The patient responded well to fluconazole therapy unlike the only known previous
      report of C. albidus in a cat. The unusual cytologic morphology in this case
      underscores the need for ancillary testing apart from microscopy for fungal
      identification. Though C. albidus should be considered as a potential feline
      pathogen, confirmation with PCR is recommended when such rare non-neoformans
      species are encountered.

PMID- 28756538
TI  - Quantitative anatomy of the growing quadratus lumborum in the human foetus.
AB  - PURPOSES: The purpose of the study was to quantitatively evaluate the size of the
      quadratus lumborum and to precisely display its growth dynamics in the human
      foetus. MATERIALS AND METHODS: Using anatomical dissection, digital-image
      analysis (NIS Elements AR 3.0) and statistical analysis (Student's t test,
      regression analysis), the length, width, surface area, and cross-sectional area
      of the quadratus lumborum were measured, and the width-to-length ratio was
      calculated in 58 human foetuses of both sexes (26?, 32?) aged 16-27 weeks.
      RESULTS: Neither sex nor right-left significant differences were found in
      relation with the numerical data of the growing quadratus lumborum. The length,
      width, and cross-sectional area of the quadratus lumborum muscle increased
      logarithmically, while its surface area increased proportionately to fetal age.
      The following growth models were computed for the quadratus lumborum: y = -70.397
      + 68.501 * ln(age) +/- 1.170 for length, y = -20.435 + 8.815 * ln(age) +/- 0.703
      for width, y = -196.035 + 14.838 * age +/- 13.745 for surface area, and y = 
      48.958 + 20.909 * ln(age) +/- 1.100 for cross-sectional area. CONCLUSIONS: The
      fetal quadratus lumborum reveals neither sex nor bilateral differences. An
      increase in length and width of the growing quadratus lumborum follows in a
      commensurate fashion. The quadratus lumborum grows logarithmically with respect
      to its length, width, and cross-sectional area, and proportionately to age with
      respect to its surface area.

PMID- 28756539
TI  - Intraspinal intradural variations of nerve roots.
AB  - PURPOSE: The aim of this work is to point out the intraspinal anatomical
      variations of nerve roots and their possible participation in radiculopathy.
      METHODS: The anatomical study was performed in 33 cadavers. There were 25 male
      cadavers aged 30-75 years and 8 female cadavers aged 45-77 years, with a mean age
      of 46.5 years to 24 h from death. All intradural rami communicantes between nerve
      roots were excised and examined histologically for the presence or absence of
      nervous tissue. The type of the plexus was defined by subtracting from the root
      C2. RESULTS: Findings of the normotype of plexus formation occurred in 24 cases
      (72.7%). Variations in its formation were observed in nine cases (27.3%). The
      prefixed type was observed in six cases (18.2%), postfixed type in three cases
      (9.1%). The formation of isolated prefixed or postfixed type of the brachial and
      lumbosacral plexus was not observed. Anatomical preparations revealed intradural
      variations in all cases of the lumbosacral plexus, 22 times (66.7%) in cases of
      cervical roots, and in the thoracic region seven times (21.2%). Variations
      occurred more frequently in variations of plexus formation. CONCLUSIONS: This
      study allowed us to identify and describe unpublished intraspinal intradural
      anatomical variations of nerve roots, and their interrelationships throughout the
      spinal canal with their potential influence on the clinical picture. Anatomical
      preparations revealed a higher incidence of intraspinal intradural variations,
      particularly between sacral roots. Reliance of their incidence of the plexus type
      was observed.

PMID- 28756540
TI  - Severe ulcerative colitis: predictors of response and algorithm proposal for
      rescue therapy.
AB  - BACKGROUND: There is no agreeing if rescue therapy can avoid short-term colectomy
      in patients treated for severe steroid-refractory ulcerative colitis. AIMS: The
      aim of our study was to identify predictors of response to infliximab and
      cyclosporine A. METHODS: In this cross-sectional study, 49 patients with severe
      ulcerative colitis were included. Response to therapy was defined as three or
      more point reductions in Mayo score after 6 months of treatment and avoidance of
      colectomy after 1 year. The predictors analysed were gender, age, time from
      ulcerative colitis diagnosis, months of steroid or/and azathioprine therapy
      before onset of the severe phase, smoking habits, extension of the disease,
      laboratory analyses and Mayo score. RESULTS: Patients treated with infliximab
      showed a statistically significant higher response rate in case of moderate Mayo
      score (P = 0.04). Ex-smokers had very low chance of response to infliximab (P =
      0.03). In the group treated with cyclosporine A, patients with C-reactive protein
      >3 mg/L had a response rate significantly higher than those with C-reactive
      protein <3 mg/L (P = 0.03); those with negative C-reactive protein and moderate
      Mayo score did not responded to therapy, while in the ones with elevated C
      reactive protein and/or severe Mayo score, 15 versus 4 responded (P = 0.008).
      CONCLUSIONS: Our data suggest that cyclosporine A is advisable in ex-smokers. In
      never smokers or active smokers, infliximab can be prescribed in case of Mayo
      score <=10 and/or negative CRP, while cyclosporine A is indicated in case of Mayo
      score >10 and positive CRP.

PMID- 28756541
TI  - Accurate and dynamic predictive model for better prediction in medicine and
      healthcare.
AB  - INTRODUCTION: Information and communication technologies (ICTs) have changed the
      trend into new integrated operations and methods in all fields of life. The
      health sector has also adopted new technologies to improve the systems and
      provide better services to customers. Predictive models in health care are also
      influenced from new technologies to predict the different disease outcomes.
      However, still, existing predictive models have suffered from some limitations in
      terms of predictive outcomes performance. AIMS AND OBJECTIVES: In order to
      improve predictive model performance, this paper proposed a predictive model by
      classifying the disease predictions into different categories. To achieve this
      model performance, this paper uses traumatic brain injury (TBI) datasets. TBI is
      one of the serious diseases worldwide and needs more attention due to its
      seriousness and serious impacts on human life. CONCLUSION: The proposed
      predictive model improves the predictive performance of TBI. The TBI data set is
      developed and approved by neurologists to set its features. The experiment
      results show that the proposed model has achieved significant results including
      accuracy, sensitivity, and specificity.

PMID- 28756542
TI  - Bioethanol Production from Soybean Residue via Separate Hydrolysis and
      Fermentation.
AB  - Bioethanol was produced using polysaccharide from soybean residue as biomass by
      separate hydrolysis and fermentation (SHF). This study focused on pretreatment,
      enzyme saccharification, and fermentation. Pretreatment to obtain monosaccharide
      was carried out with 20% (w/v) soybean residue slurry and 270 mmol/L H2SO4 at 121
      degrees C for 60 min. More monosaccharide was obtained from enzymatic hydrolysis
      with a 16 U/mL mixture of commercial enzymes C-Tec 2 and Viscozyme L at 45 
      degrees C for 48 h. Ethanol fermentation with 20% (w/v) soybean residue
      hydrolysate was performed using wild-type and Saccharomyces cerevisiae KCCM 1129
      adapted to high concentrations of galactose, using a flask and 5-L fermenter.
      When the wild type of S. cerevisiae was used, an ethanol production of 20.8 g/L
      with an ethanol yield of 0.31 g/g consumed glucose was obtained. Ethanol
      productions of 33.9 and 31.6 g/L with ethanol yield of 0.49 g/g consumed glucose
      and 0.47 g/g consumed glucose were obtained in a flask and a 5-L fermenter,
      respectively, using S. cerevisiae adapted to a high concentration of galactose.
      Therefore, adapted S. cerevisiae to galactose could enhance the overall ethanol
      fermentation yields compared to the wild-type one.

PMID- 28756543
TI  - ESI-MS of Cucurbituril Complexes Under Negative Polarity.
AB  - Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool to study
      host-guest supramolecular interactions. ESI-MS can be used for detailed gas-phase
      reactivity studies, to clarify the structure, or simply to verify the formation
      of complexes. Depending on the structure of the host and of the guest, negative
      and/or positive ESI are used. Here we report the unexpected formation of host
      guest complexes between cucurbit[n]urils (n = 7, 8, CB[n]) and amine, styryl
      pyridine, and styryl pyridine dimer cations, under negative ESI. Non-complexed
      CB[n] form double charged halide (Br-, Cl-, F-) adducts. Under negative ESI,
      halide ions interact with CB[n] outer surface hydrogen atoms. One to one host
      guest complexes (1:1) of CB[n] with positive charged guests were also observed as
      single and double charged ions under negative ESI. The positive charge of guests
      is neutralized by ion-pairing with halide anions. Depending on the number of
      positive charges guests retain in the gas phase, one or two additional halide
      ions are required for neutralization. Complexes 1:2 of CB[8] with styryl
      pyridines retain two halide ions in the gas phase, one per guest. Styryl pyridine
      dimers form 1:1 complexes possessing a single extra halide ion and therefore a
      single positive charge. Negative ESI is sensitive to small structural differences
      between complexes, distinguishing between 1:2 complexes of styryl pyridine-CB[8]
      and corresponding 1:1 complexes with the dimer. Negative ESI gives simpler
      spectra than positive ESI and allows the determination of guest charge state of
      CB[n] complexes in the gas phase. Graphical Abstract ?.

PMID- 28756544
TI  - Retro analog concept: comparative study on physico-chemical and biological
      properties of selected antimicrobial peptides.
AB  - Increasing drug resistance of common pathogens urgently needs discovery of new
      effective molecules. Antimicrobial peptides are believed to be one of the
      possible solutions of this problem. One of the approaches for improvement of
      biological properties is reversion of the sequence (retro analog concept). This
      research is based on investigation of antimicrobial activity against Gram
      positive, Gram-negative bacteria, and fungi, hemolysis of erythrocytes,
      interpretation of the circular dichroism spectra, measurement of counter-ion
      content, and assessment of the peptide hydrophobicity and self-assembly using
      reversed-phase chromatography. The experiments were conducted using the following
      peptides: aurein 1.2, CAMEL, citropin 1.1, omiganan, pexiganan, temporin A, and
      their retro analogs. Among the compounds studied, only retro omiganan showed an
      enhanced antimicrobial and a slightly increased hemolytic activity as compared to
      parent molecule. Moreover, retro pexiganan exhibited high activity towards
      Klebsiella pneumoniae, whereas pexiganan was in general more or equally active
      against the rest of tested microorganisms. Furthermore, the determined activity
      was closely related to the peptide hydrophobicity. In general, the reduced
      hemolytic activity correlates with lower antimicrobial activity. The tendency to
      self-association and helicity fraction in SDS seems to be correlated. The
      normalized RP-HPLC-temperature profiles of citropin 1.1 and aurein 1.2, revealed
      an enhanced tendency to self-association than that of their retro analogs.

PMID- 28756545
TI  - Single emergency room measurement of neutrophil/lymphocyte ratio for early
      detection of acute kidney injury (AKI).
AB  - Neutrophil-to-lymphocyte ratio (NLR) is considered a readily available biomarker
      of systemic inflammation. An association between elevated NLR and adverse
      outcomes in a variety of medical and surgical conditions including CKD has been
      demonstrated in several studies. In this study, we evaluated the accuracy of
      single Emergency Department (ED) measurement of NLR for early diagnosis of acute
      kidney injury (AKI). We prospectively studied 294 patients aged 71.6 +/- 17. We
      measured NLR at presentation to the ED. AKI is defined as a new-onset 1.5-fold or
      more increase in serum creatinine or a 25% decrease in estimated GFR sustained
      for at least 3 days despite volume resuscitation. The primary outcome is AKI.
      Secondary outcome is in-hospital mortality. A multivariate model and ROC analysis
      were performed to evaluate the association and eventual predictive capacity of
      NLR for the outcomes. 36 patients (12.2%) developed AKI and 26 (9%) died, 8 (22%)
      of the AKI group and 17 patients (7%) of the non-AKI group. The Mean NLR is
      significantly higher in AKI compare to non-AKI patients (11.7 +/- 15.2 vs 6.45 +/
      7.19, p = 0.048). A multivariate model adjusted for age, gender, blood pressure,
      plasma albumin and hemoglobin levels confirms that the NLR is higher in AKI
      patients (p = 0.031). Receiver operating characteristics curve reveals an AUC of
      0.715 (95% CI 0.63-0.8) sensitivity 0.78, specificity 0.65, and OR 6.423 (CI
      2.659-16.026) for a cutoff value of NLR 5.5. The relation between NLR and in
      hospital mortality is not statistically significant (p = 0.92). Single ED
      measurement of NLR might be a useful tool for early diagnosis of AKI. This
      finding is particularly important in light of the low cost and widespread
      availability of NLR, especially compared with other biomarkers currently under
      study in the context of AKI.

PMID- 28756547
TI  - Pyoderma gangrenosum near a cystostomy catheter.

PMID- 28756548
TI  - Optimized statistical parametric mapping procedure for NIRS data contaminated by
      motion artifacts : Neurometric analysis of body schema extension.
AB  - This study investigated the spatial distribution of brain activity on body schema
      (BS) modification induced by natural body motion using two versions of a hand
      tracing task. In Task 1, participants traced Japanese Hiragana characters using
      the right forefinger, requiring no BS expansion. In Task 2, participants
      performed the tracing task with a long stick, requiring BS expansion. Spatial
      distribution was analyzed using general linear model (GLM)-based statistical
      parametric mapping of near-infrared spectroscopy data contaminated with motion
      artifacts caused by the hand-tracing task. Three methods were utilized in series
      to counter the artifacts, and optimal conditions and modifications were
      investigated: a model-free method (Step 1), a convolution matrix method (Step 2),
      and a boxcar-function-based Gaussian convolution method (Step 3). The results
      revealed four methodological findings: (1) Deoxyhemoglobin was suitable for the
      GLM because both Akaike information criterion and the variance against the
      averaged hemodynamic response function were smaller than for other signals, (2) a
      high-pass filter with a cutoff frequency of .014 Hz was effective, (3) the
      hemodynamic response function computed from a Gaussian kernel function and its
      first- and second-derivative terms should be included in the GLM model, and (4)
      correction of non-autocorrelation and use of effective degrees of freedom were
      critical. Investigating z-maps computed according to these guidelines revealed
      that contiguous areas of BA7-BA40-BA21 in the right hemisphere became
      significantly activated ([Formula: see text], [Formula: see text], and [Formula:
      see text], respectively) during BS modification while performing the hand-tracing
      task.

PMID- 28756546
TI  - Thromboprophylaxis with enoxaparin and direct oral anticoagulants in major
      orthopedic surgery and acutely ill medical patients: a meta-analysis.
AB  - Subjects undergoing major orthopedic surgery and acutely ill hospitalized medical
      patients represent a population at medium-high risk for venous thromboembolism
      (VTE). They are treated with low molecular weight heparin (LMWH) and direct oral
      anticoagulants [DOACs] for VTE prevention. We conducted a meta-analysis of phase
      III randomized clinical trials evaluating LMWH enoxaparin versus DOACs for
      prophylaxis of VTE by combining studies including patients undergoing elective
      total hip and knee replacement surgery, and acutely ill hospitalized medical
      subjects. Studies were searched using PubMed, MEDLINE, and EMBASE databases until
      December 2016. Differences in clinical outcomes for efficacy and safety endpoints
      between treatment groups were expressed as risk differences with 95% confidence
      intervals (95% CI), using random effects regression models. Fourteen RCTs were
      considered (60,467 subjects). Overall mortality, symptomatic deep venous
      thrombosis, non-fatal pulmonary embolism (PE) major bleeding (MB) and clinically
      relevant non-major bleeding (CRNMB) are not different between treatment regimens.
      Treatment with LMWH enoxaparin is associated with a lower risk of fatal PE plus
      VTE-related death compared therapy with DOACs (RD = 0.040%, 95% CI 0.001-0.080%,
      p = 0.0434). Subgroup analysis shows an incidence of MB (RD = 0.181%, 95% CI
      0.029-0.332%, p = 0.0033) and CRNMB (RD = 0.546%, 95% CI 0.009-1.082%, p =
      0.0462) in patients treated with 40 mg OD enoxaparin compared to DOACs. In major
      orthopedic surgery and acutely ill hospitalized medical patients, DOACs do not
      offer clear advantages in terms of clinical efficacy compared to enoxaparin. The
      advantage of the latter in terms of major and CRNMB, when used at a dose of 40
      mg, is statistically significant, but small in terms of clinical relevance.

PMID- 28756549
TI  - A Scoping Review of Health Disparities in Autism Spectrum Disorder.
AB  - Individuals with autism spectrum disorder (ASD) experience increased morbidity
      and decreased life expectancy compared to the general population, and these
      disparities are likely exacerbated for those individuals who are otherwise
      disadvantaged. We conducted a review to ascertain what is known about health and
      health system quality (e.g., high quality care delivery, adequate care access)
      disparities in ASD. Nine studies met final inclusion criteria. Seven studies
      identified racial disparities in access to general medical services for children
      with ASD. No studies examined disparities in health outcomes or included older
      adults. We present a model of health disparities (Fundamental Causes Model) that
      guides future research. Additional work should examine health disparities, and
      their causal pathways, in ASD, particularly for older adults.

PMID- 28756551
TI  - Family-centered Services for Children with ASD and Limited Speech: The
      Experiences of Parents and Speech-language Pathologists.
AB  - Although family-centered services have long been discussed as essential in
      providing successful services to families of children with autism spectrum
      disorder (ASD), ideal implementation is often lacking. This study aimed to
      increase understanding of how families with children with ASD and limited speech
      receive services from speech-language pathologists (SLPs). 99 parents of children
      with ASD and limited speech and 211 SLPs who served children with ASD and limited
      speech completed questionnaires measuring their experiences with the provision of
      family-centered services. Findings revealed that parents and SLPs differed in
      their views on the degree to which family-centered services were being
      implemented. Clinical implications and future research directions are discussed
      in order to promote continued growth in the acquisition of family-centered
      skills.

PMID- 28756550
TI  - A Pilot Study Assessing Performance and Visual Attention of Teenagers with ASD in
      a Novel Adaptive Driving Simulator.
AB  - Individuals with Autism Spectrum Disorder (ASD), compared to typically-developed
      peers, may demonstrate behaviors that are counter to safe driving. The current
      work examines the use of a novel simulator in two separate studies. Study 1
      demonstrates statistically significant performance differences between
      individuals with (N = 7) and without ASD (N = 7) with regards to the number of
      turning-related driving errors (p < 0.01). Study 2 shows that both the
      performance-based feedback group (N = 9) and combined performance- and gaze
      sensitive feedback group (N = 8) achieved statistically significant reductions in
      driving errors following training (p < 0.05). These studies are the first to
      present results of fine-grained measures of visual attention of drivers and an
      adaptive driving intervention for individuals with ASD.

PMID- 28756552
TI  - Perspectives of University Students with Autism Spectrum Disorder.
AB  - Students with autism spectrum disorder (ASD) are at heightened risk of post
      secondary educational failure and account for approximately 1% of students in
      post-secondary education. Findings from an on-line survey of students with ASD
      attending university in Australian are reported in this study. Respondents
      indicated high rates of academic and non-academic difficulties but low usage of
      supports. Ratings for supports were idiosyncratic, and some students indicated
      discomfort from using supports or disclosing their disability. Those students who
      delayed their disclosure accessed fewer supports and reported a poorer overall
      university experience. Recommendations were made including the need for better
      transition support and alternative strengths based approaches that use more
      flexible and individualised curriculum designs.

PMID- 28756553
TI  - Resource use efficiency of broiler production in tunnel-ventilated environmental
      control vis-a-vis open-sided conventional shed during summer.
AB  - Present study was conducted to assess the resource use efficiency of broilers
      production, in tunnel-ventilated environment control (ECBH) and open-sided
      conventional (OSCBH) house under different stocking densities. Different
      treatments comprised of T 0 (birds with floor space, 1.0/ft2/bird in open-sided
      conventional broiler house (OSCBH) as control, while different treatments in
      tunnel-ventilated environment control broiler house (ECBH) were T 1, T 2, T 3, T
      4 and T 5 with floor space of 1.0, 0.9, 0.8, 0.7and 0.6 ft2 per bird,
      respectively. The results of shed microclimate indicated that shed temperature
      and temperature humidity index (THI) at 12:00 and 15:00 IST and maximum and
      minimum temperature in OSCBH were significantly (p <= 0.05) higher than ECBH.
      Litter moisture and pH did not differ significantly and were within permissible
      limits in both OSCBH and ECBH. Final body weight, body weight gain, feed intake
      were significantly higher and FCR, PER and EER were significantly better in ECBH
      than OSCBH (T 0) even at 10% increase in stocking density (T 2). Margin of
      receipt in T 2 in ECBH from sale of live bird/unit area and kilogram live weight
      per unit area was maximum which was Rs. 5.08/- and 3.56/- higher than T 0 for
      OSCBH.

PMID- 28756554
TI  - Do traditional sheep breeders perform conscious selection? An example from a
      participatory breeding program of Morada Nova sheep.
AB  - The implementation of sustainable breeding programs requires genetic breeding
      strategies that are appropriate for the reality production systems. It is also
      essential that the choice of animal selection criteria be based on breeders'
      knowledge and objectives. This work is an ethno-zootechnical study of the Morada
      Nova sheep breed and its crossbreeds. The goals of this study were to register
      and analyze indigenous breeders' knowledge and practices regarding animal
      selection criteria and to generate technical information to support a
      participatory breeding program of the breed. This study was conducted in the
      Morada Nova municipality in the state of Ceara, Brazil. Semi-structured
      interviews were evaluated using two groups of individuals, purebred Morada Nova
      sheep breeders (RMN, n = 13) and breeders of Morada Nova crossbreeds (MMN, n =
      48). Interview questions were used to identify local selection criteria adopted
      by each group in the choice of animals for breeding. Data from the interviews
      were submitted to frequency distribution analysis and the Shapiro-Wilk test to
      verify their distribution. Later, the Kruskal-Wallis test was used to compare the
      two groups of farmers based on that information, in addition to multivariate
      statistical analysis and evaluation of Smith salience index. Breeders in the RMN
      group used selection criteria related to breed standards, such as pelage color.
      In contrast, breeders of the MMN group used criteria related to productivity,
      such as body conformation and milk production. Breeders should be engaged in the
      development of breeding programs, and it is important to consider their
      preferences and objectives when evaluating breeding animals.

PMID- 28756555
TI  - Children's and Parents' Ability to Tolerate Child Distress: Impact on Cognitive
      Behavioral Therapy for Pediatric Obsessive Compulsive Disorder.
AB  - The present study explored the concept of tolerance for child distress in 46
      children (ages 5-8), along with their mothers and fathers, who received family
      based CBT for OCD. The study sought to describe baseline tolerance, changes in
      tolerance with treatment, and the predictive impact of tolerance on symptom
      improvement. Tolerance was rated by clinicians on a single item and the CY-BOCS
      was used to measure OCD severity. Descriptive results suggested that all
      participants had some difficulty tolerating the child's distress at baseline
      while paired t tests indicated large improvements were made over treatment (d =
      1.2-2.0). Fathers' initial tolerance was significantly related to symptom
      improvement in a multivariate regression as were fathers' and children's changes
      in distress tolerance over the course of treatment. Overall, results provide
      support for examining tolerance of child distress including its predictive impact
      and potential as a supplemental intervention target.

PMID- 28756556
TI  - The Validity of the Screen for Child Anxiety Related Emotional Disorders Revised
      (SCARED-R) Scale and Sub-Scales in Swedish Youth.
AB  - We evaluated the clinical utility of the Swedish SCARED-R in child- and
      adolescent psychiatric outpatients (n = 239) and validated it against
      Longitudinal Expert All Data (LEAD) DSM IV diagnoses based on the Children's
      Schedule for Affective Disorders and Schizophrenia (KSADS) and subsequent
      clinical work-up and treatment outcome. The SCARED-R total score and subscales
      had acceptable sensitivity/specificity for child and parent reports for cut-offs
      based on Receiver Operating Characteristics (ROC) curves, with mostly moderate
      area under the curve. Sensitivity ranged from 75% (parent rated social anxiety)
      to 79% [child rated Generalized Anxiety Disorder (GAD)]. Specificity, ranged from
      60% for child-rated GAD to 88% for parent rated social anxiety. Parent-child
      agreement was moderate, and each informant provided unique information
      contributing to most diagnoses. In conclusion, the SCARED-R is useful for
      screening anxiety symptoms in clinical populations. However, it cannot replace
      interview based diagnoses, nor is it adequate to use just one informant.

PMID- 28756557
TI  - Effects of Central Nervous System Drugs on Recovery After Stroke: A Systematic
      Review and Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND AND OBJECTIVE: Pilot trials have suggested that pharmacotherapy may
      aid stroke recovery. The aim of this study was to systematically review the
      effects of antidepressants, anti-Alzheimer drugs, anti-Parkinson drugs, central
      nervous system (CNS) stimulants and piracetam on gross motor function, cognition,
      disability, dependency and quality of life (QOL) after stroke. METHODS: PubMed,
      EMBASE and the Cochrane Central Register of Controlled Trials databases were
      searched, and 44 randomized controlled trials that compared outcomes of interest
      between drug treatment and placebo or no treatment were included. For each study,
      standardized mean difference (SMD) or mean difference (MD) with 95% confidence
      interval (CI) were calculated. Meta-analyses were conducted to pool results using
      either the fixed-effects or random-effects model. RESULTS: Selective serotonin
      reuptake inhibitors (SSRIs) improved gross motor function (SMD 0.54, 95% CI 0.22
      0.85; three studies), disability (SMD 0.49, 95% CI 0.32-0.66; 14 studies) and QOL
      (MD 6.46, 95% CI 4.71-8.22; two studies), but there was insufficient evidence for
      their use in enhancing global cognition (SMD 0.23, 95% CI -0.01 to 0.46; five
      studies) and dependency (risk ratio 0.81, 95% CI 0.68-0.97; one fluoxetine
      study). In particular, gross motor function was improved by fluoxetine (SMD 0.64,
      95% CI 0.31-0.98; two studies), while disability was improved by paroxetine (SMD
      1.05, 95% CI 0.63-1.46; two studies), citalopram (SMD 0.51, 95% CI 0.08-0.93; two
      studies) and fluoxetine (SMD 0.41, 95% CI 0.22-0.60; nine studies). There is
      insufficient evidence for the use of anti-Alzheimer drugs, anti-Parkinson drugs,
      CNS stimulants and piracetam to promote stroke recovery. CONCLUSIONS:
      Administration of SSRIs may improve gross motor function, reduce disability and
      enhance QOL for patients recovering from stroke.

PMID- 28756558
TI  - The "old" 15 mm renal stone size limit for RIRS remains a clinically significant
      threshold size.
AB  - PURPOSE: To investigate the performance of retrograde intrarenal surgery (RIRS)
      for the 1-2 cm renal stone size range in comparison to smaller stones. MATERIALS
      AND METHODS: From a data base of 3000 ureteroscopies between 2004 and 2014, 635
      consecutive patients underwent RIRS for renal stones. Patients were divided to
      three groups according to their renal stone size (<10, 10-15, 15-20 mm).
      Preoperative, operative, stone free rate (SFR) and follow-up data were analyzed
      and compared. RESULTS: The SFR for the three groups was 94.1, 90.1 and 85%,
      respectively. Patients with renal stone size above 15 mm had a statistically
      significantly lower SFR. The efficiency quotient calculated for stones larger and
      smaller than 15 mm was 83.9 vs. 91.8%, respectively (p < 0.01). The mean
      operative time and hospital stay were longer for patients with renal stones
      larger than 15 mm (73.6 +/- 29.9 vs. 53 +/- 19.4 min, p < 0.01 and 2.2 +/- 2 vs.
      1.8 +/- 1.8 days, p = 0.031, respectively). Moreover, the complication rate was
      almost two times higher (10 vs 5.4%, p = 0.08). Concomitant ureteral stones and
      older age were independent predictors of failure in the large stone group.
      CONCLUSIONS: While the overall SFR following RIRS for renal stones up to 2 cm is
      generally high, the SFR for 15-20 mm stones is significantly lower, with a longer
      operating time and hospital stay, and a higher complication rate.

PMID- 28756559
TI  - Determination and validation of LJ-2698, a potent human A3 adenosine receptor
      antagonist, in rat plasma by liquid chromatography-tandem mass spectrometry and
      its application in pharmacokinetic study.
AB  - LJ-2698, a highly potent human A3 adenosine receptor antagonist with nucleoside
      structure, was designed to have a minimal species dependence. For further pre
      clinical studies, analytical method for the detection of LJ-2698 in rat plasma
      was developed by liquid chromatography-tandem mass. Plasma samples were processed
      by protein precipitation method with acetonitrile, using losartan as the internal
      standard (IS). Chromatographic separation was carried out using a Kinetex C18
      column (100 * 4.6 mm; 100 A; 2.6 MU) with acetonitrile/water with 0.2% (v/v)
      formic acid (65:35, v/v) in the isocratic mode at a flow rate of 0.4 mL/min. Mass
      spectrometric detection in multiple reaction monitoring mode was performed with
      positive electrospray ionization. The mass transitions of LJ-2698 and IS were m/z
      412.3 -> 294.1 and m/z 423.1 -> 207.2, respectively. The calibration curves were
      linear in the range 5.00-5000 ng/mL (r 2 >= 0.998). The lower limit of
      quantification was established as 5.00 ng/mL. Within- and between-run precisions
      were <7.01%, as relative standard deviation; and accuracies were in the range
      3.37-3.64%, as relative error. The validated method was successfully applied to
      its pharmacokinetic evaluation after intravenous and oral administration in rats,
      and the dose-dependent pharmacokinetic behavior of LJ-2698 was elucidated for the
      first time.

PMID- 28756560
TI  - In silico analysis of the cyanobacterial lectin scytovirin: new insights into
      binding properties.
AB  - Scytovirin is a lectin isolated from the cyanobacterium Scytonema varium that has
      shown activity against HIV, SARS coronavirus and Zaire Ebola virus. Its 95 amino
      acids are divided into two structural domains (SD), the first spanning amino
      acids 1-48 (SD1) and the second 49-95 (SD2). Interestingly, the domains are
      nearly identical but differ in their affinities for carbohydrates. With the aim
      of enhancing understanding of the binding properties of scytovirin, we performed
      molecular dynamics (MD) simulations of scytovirin complexed with Man4. We set up
      three systems: (i) Man4 bound to both domains (SD1 + SD2) using the full-length
      protein; (ii) Man4 bound to an incomplete protein, containing only SD1 and (iii)
      Man4 bound to an incomplete protein containing only SD2. Contrary to other
      reports, binding free energy results suggest that Man4 can bind simultaneously to
      SD1 and SD2 binding regions, but SD1 individually has the best values of energy
      and the best affinity for Man4. Decomposition of the binding free energy showed
      that the residues that interact with Man4 were different in the three systems,
      suggesting that the binding mechanism of Man4 varies between full-length protein,
      SD1 and SD2. The results presented here may help to formulate strategies to use
      scytovirin and promote mutagenesis studies to improve the antiviral activity of
      scytovirin.

PMID- 28756561
TI  - Evidence of dengue and chikungunya virus co-infection and circulation of multiple
      dengue serotypes in a recent Indian outbreak.
AB  - In India, dengue endemic areas overlap with chikungunya-affected areas and both
      the viruses are transmitted by same vector, Aedes aegypti - thereby increasing
      opportunity of co-infection by both viruses. Present study was carried out to
      understand the DENV-CHIKV infection dynamics during recent outbreaks in eastern
      India (West Bengal state) and its implication on disease manifestations. Blood
      was collected from 326 symptomatic febrile patients. Patients' serum was
      subjected to serological diagnosis for presence of anti-dengue-IgM, anti
      chikungunya-IgM antibodies and dengue-NS1 antigen by ELISA. Viral RNA was
      extracted, and presence of dengue virus (DENV) and chikungunya virus (CHIKV)
      genome, their viral load (VL), and serotype among infected patients' plasma was
      determined by real-time qRT-PCR. Statistical analysis was performed by using EPI
      INFO software. DENV and CHIKV were detected in 54% and 33% of symptomatic
      patients respectively, among whom 23% were harboring both viruses. WHO classified
      warning signs were detected among 64% DENV patients and 61% DENV-CHIKV double
      infected patients. Patients with warning signs always had much higher DEN VL than
      those without warning signs. Hemorrhagic manifestation and abdominal pain was
      found in significantly higher frequency among patients with high dengue VL
      (>10,000 copies/ml). DENV2 was the most predominant serotype among monotypic
      dengue patients, whereas DENV2-DENV4 combination was most prevalent among
      patients infected with dual dengue serotypes. This study indicated that DENV
      CHIKV double infection and high dengue VL contributed towards severe disease
      manifestations among infected patients. DENV2 and DENV2-DENV4 combination were
      the most prevalent serotype(s) found in current outbreak.

PMID- 28756562
TI  - Life history written in blood: erythrocyte parameters in a small hibernator, the
      edible dormouse.
AB  - The oxygen delivery system is one major determinant of the performance of
      vertebrates and responds sensitively to a variety of internal and environmental
      factors. To understand physiological mechanisms underlying variations of fitness,
      we investigated effects of demanding conditions associated with certain life
      history events, food availability, and population density on the oxygen delivery
      system in free-ranging edible dormice (Glis glis). We sampled blood (n = 248) and
      urine (n = 319), performed an erythrocyte haemogram and visually determined the
      presence of haemoglobinuria. Reproduction leads to increased mortality in edible
      dormice and our study now reveals severe haematological impairments during
      reproduction that were associated with nutrient and energy deficits and stress.
      These effects were even more pronounced in subsequent reproductive years,
      indicating prolonged physiological impairment. Under limited food availability,
      the rate of erythrocyte generation was reduced. This seems to be part of an
      energy saving strategy instead of representing a poor body condition as survival
      probability in this species is high in years of low food availability. A high
      prevalence ratio of haemoglobinuria (up to 85%) at the end of the active season
      indicated amplified erythrocyte destruction through haemolysis. This may be the
      result of a preparative mechanism to avoid massive oxidative damage during the
      long hibernation period. Most ecophysiological studies so far focus on single
      erythrocyte parameters on a short time scale, which could be misleading. Our
      results clearly highlight that a wide-array RBC approach is a powerful tool for
      investigating mechanisms underlying physiological performance and fitness, also
      for other vertebrate taxa.

PMID- 28756563
TI  - The zygomatic implant perforated (ZIP) flap: a new technique for combined
      surgical reconstruction and rapid fixed dental rehabilitation following low-level
      maxillectomy.
AB  - This aim of this report is to describe the development and evolution of a new
      surgical technique for the immediate surgical reconstruction and rapid post
      operative prosthodontic rehabilitation with a fixed dental prosthesis following
      low-level maxillectomy for malignant disease.The technique involves the use of a
      zygomatic oncology implant perforated micro-vascular soft tissue flap (ZIP flap)
      for the primary management of maxillary malignancy with surgical closure of the
      resultant maxillary defect and the installation of osseointegrated support for a
      zygomatic implant-supported maxillary fixed dental prosthesis.The use of this
      technique facilitates extremely rapid oral and dental rehabilitation within a few
      weeks of resective surgery, providing rapid return to function and restoring
      appearance following low-level maxillary resection, even in cases where
      radiotherapy is required as an adjuvant treatment post-operatively. The ZIP flap
      technique has been adopted as a standard procedure in the unit for the management
      of low-level maxillary malignancy, and this report provides a detailed step-by
      step approach to treatment and discusses modifications developed over the
      treatment of an initial cohort of patients.

PMID- 28756564
TI  - Production of dodecanedioic acid via biotransformation of low cost plant-oil
      derivatives using Candida tropicalis.
AB  - Dodecanedioic acid (DDA) is highly useful to the chemical industry as a versatile
      precursor for producing the polyamide nylon-6,12, which is used for many
      technical applications, such as heat and chemical-resistant sheaths. However, DDA
      synthesis has several drawbacks, such as high energy input and cost-intensive
      removal of by-products. Therefore, alternative bio-based production routes are
      required due to increasing industrial demand for green chemicals and renewable
      products. Candida tropicalis converts petrochemical-based n-dodecanes to the
      corresponding dicarboxylic acids by targeted functionalization. To increase
      sustainability of the DDA production process, we tested dodecanoic acid methyl
      ester, which can be easily obtained from transesterification of coconut oil, in
      whole-cell biotransformation by C. tropicalis. By modifying selected process
      parameters, a final DDA concentration of 66 g/L was achieved using a highly
      reliable, small-scale bioreactor system. Crucial process development included a
      gradual pH shift, an optimized substrate feeding strategy, and monitoring the
      transcriptional profile.

PMID- 28756565
TI  - Establishing marine protected areas in Sweden: Internal resistance versus global
      influence.
AB  - In the past decade, marine protected areas (MPAs) have become an increasingly
      used tool for science-based conservation and adaptive management of marine
      biodiversity and related natural resources. In this review paper, we report on
      rather complete time-course series (55 years uninterrupted) focusing on
      comparison of the strong difference, in number and area, in establishing marine
      (56 MNRs) and terrestrial (4284 TNRs) nature reserves in Sweden versus marine
      (7001 MPAs) and terrestrial (132742 TPAs) protected areas globally. Sweden
      appears to follow the overall global time trends. The large backlog of MPAs in
      relation to TPAs is due to several possible reasons, such as (i) unclear marine
      jurisdiction, (ii) marine conservation policies and programs developed later than
      terrestrial, (iii) higher costs for marine conservation management, (iv)
      conflicts in marine conservation, especially the fishery, and (v) the general
      public's historically weak awareness of the status of the marine environment.

PMID- 28756566
TI  - PTEN hamartoma of the soft tissue: the initial manifestation of an underlying
      PTEN hamartoma tumor syndrome in a 4-year-old female.
AB  - A 4-year-old female was referred to pediatric orthopedic surgery for left leg
      pain and limping for 3 months following a motor vehicle collision. Recently, the
      patient's mother had noted left knee swelling and dragging of the left leg when
      walking. Past medical history was significant for hip dysplasia with slight leg
      length discrepancy. The patient was otherwise healthy. Physical examination was
      remarkable for left pre-patellar soft tissue fullness with normal range of
      motion. There was no warmth or tenderness. Subsequent ultrasound revealed a
      heterogeneous soft tissue mass superior and medial to the patella with a moderate
      degree of internal vascularity. MR exhibited a heterogeneous soft tissue mass
      with heterogeneous signal on both T1- and T2-weighted images centered within the
      vastus medialis obliquus muscle infiltrating the quadriceps tendon. Excisional
      biopsy was performed with a histopathologic diagnosis of fibroadipose tissue with
      anomalous vessels, suggestive of phosphatase and tensin homolog (PTEN) hamartoma
      of the soft tissue (PHOST). The patient was found to be positive for the PTEN
      gene mutation on genetic testing. The child was also determined to be
      macrocephalic, a major criterion for PTEN hamartoma tumor syndrome (PHTS). The
      geneticist advised the patient to undergo yearly physical examinations and early,
      routine surveillance for several malignancies occurring with PHTS. This case
      report presents the ultrasound and MRI appearance of a rare benign tumor
      typically appearing in pediatric patients. The strong association between PHOST
      and other soft tissue malignancies and the resulting need for life-long
      surveillance make PHOST an important pathology to recognize.

PMID- 28756567
TI  - Growth plate injury at the base of the coracoid: MRI features.
AB  - PURPOSE: To assess the MRI features of growth plate injury at the base of the
      coracoid process. MATERIALS AND METHODS: Subjects were identified through
      retrospective search of our department imaging database and teaching files and
      the teaching files of two outside academic institutions. The coracoid base growth
      plate was examined with attention to widening, irregularity, abnormal signal
      intensity of the growth plate, and the presence of adjacent soft tissue edema.
      The apposing coracoid and scapular bony surfaces were examined for signal
      intensity and morphology. RESULTS: Shoulder MRIs in eight patients with coracoid
      base growth plate disturbances were retrospectively reviewed (7 males, 1 female,
      mean age 15 years). Growth plate injury manifested as widening, irregularity and
      increased signal, apposing bony marrow edema and hypertrophy, and surrounding
      soft tissue edema. Five subjects were athletes (football, archery, basketball,
      swimming, rugby), two had a history of neuromuscular disorders, and one subject
      presented after a fall. Clinical indications included: rule out labral tear (n =
      3), rule out rotator cuff tear or fracture after fall (n = 1), nonspecific pain
      (n = 1), shoulder subluxation, rule out glenoid pathology (n = 1, patient with
      underlying neuromuscular disorder), muscular dystrophy with shoulder pain (n =
      1), and impingement (n = 1). Coracoid growth plate injury was not suspected
      clinically in any of the patients. CONCLUSION: Awareness of the imaging
      appearance of coracoid base growth plate injury can aid in a more accurate
      diagnosis of shoulder MRI studies in young pediatric athletes. While uncommon,
      coracoid growth plate injury should be considered when assessing children with
      shoulder symptomatology.

PMID- 28756568
TI  - Low-grade chondrosarcoma of the cricoid cartilage: a case report and review of
      the literature.
AB  - We report the case of a 60-year-old man with a 12-day history of vomiting
      whenever he had a meal. Computed tomography revealed a calcified mass in the
      right cricoid cartilage with intraluminal and extraluminal extension. The patient
      underwent surgical resection of the trachea with end-to-end anastomosis.
      Pathological examination of the surgical specimen showed a low-grade
      chondrosarcoma. Eighteen months after surgery, the patient is alive and disease
      free.

PMID- 28756569
TI  - Sudden hearing loss: an effectivity comparison of intratympanic and systemic
      steroid treatments.
AB  - Corticosteroid treatment has been considered the most effective treatment
      modality for sudden sensorineural hearing loss so far. Application route of
      corticosteroids may vary. We have designed a prospective randomized case
      controlled clinical trial to evaluate the effectivenesses of the different
      application routes of steroids in the treatment of SSHL. Thirty-five patients
      were distributed randomly to two groups which were treated with either 'oral' or
      'intratympanic' corticosteroids. Intratympanic steroid administration was
      performed three times every other day transtympanically. At the end of third
      month, recovery rate in the 'intratympanic' group was 84.2%, whereas in the
      'oral' group, it was 87.5%. The difference between the recovery rates was not
      statistically significant. There were no major complications related to
      transtympanic steroid administration. These findings support that intratympanic
      steroid therapy is an alternative to systemic steroid therapy in the initial
      treatment of sudden hearing loss. In addition, transtympanic technique is an easy
      to perform and safe method for delivering steroids into the inner ear.

PMID- 28756572
TI  - Patient Satisfaction and Quality of Life in People with Schizophrenia-Spectrum
      Disorders in a Rural Area.
AB  - People suffering from schizophrenia-spectrum disorders often endorse a reduced
      quality of life (QoL) as compared to the general population. There appears to be
      a lack of studies for rural catchment areas for this patient population. We
      conducted a cross-sectional study with 94 people with schizophrenia-spectrum
      disorders in a mainly rural alpine area. We used multilevel models controlled for
      covariates to analyze the data. Total service satisfaction was associated with
      psychological aspects of subjective QoL and physical well-being in our model.
      Variables characterizing autonomy and empowerment of the person seem crucial
      concerning the QoL in this population.

PMID- 28756571
TI  - Developmental differences between a Chinese and a North American isolate of the
      pinewood nematode Bursaphelenchus xylophilus (Tylenchida: Aphelenchoididae) under
      laboratory conditions.

PMID- 28756570
TI  - Sensitivity and specificity of the abbreviated profile of hearing aid benefit
      (APHAB).
AB  - Subjective hearing loss in hearing-impaired patients can be assessed by inventory
      questionnaires. The abbreviated profile of hearing aid benefit (APHAB) measures
      subjective hearing loss in four typical hearing situations (subscales). It is
      used to fit hearing aids in patients with statutory insurance in Germany. In
      addition, the unaided APHAB (APHABu) can be used as a primary diagnostic
      instrument in audiology. There are no published data regarding the sensitivity
      and specificity of the unaided APHABu. Therefore, we investigated these
      parameters for detecting hearing loss of at least 25 dB at any frequency between
      0.5 and 8.0 kHz. We used the APHABu to determine hearing loss in 245 subjects
      aged 50 years and older without any reported disease of the ears. Due to
      incomplete answering of the APHAB form, 55 subjects have been excluded. We also
      measured the pure-tone thresholds by air conduction for all octave frequencies
      between 0.5 and 8 kHz. Receiver operating characteristic (ROC) curves and the
      Youden Index were used to determine the diagnostic value of the APHABu,
      particularly sensitivity and specificity, in three different ways: (1) separately
      for ease of communication (ECu), background noise (BNu), and hearing with
      reverberation (RVu) subscales; (2) with the mean value of ECu, BNu, and RVu; and
      (3) with a logistic regression model. The area under the ROC curve was lower for
      BN only (0.83) and nearly equal for all other methods (0.87-0.89). Depending on
      how we performed the analyses, the sensitivity of the APHABu was 0.70-0.84
      (single subscales), 0.76 (mean value of ECu, BNu, and RVu), or 0.85 (logistic
      regression model). The specificity was 0.79-0.95. The use of single APHABu
      subscales for determining the sensitivity and specificity of the APHABu due to
      confusing results. In comparison, the use of the mean value of ECu, BNu, and RVu
      and the use of the logistic regression model due to equal values in the ROC
      curves but a higher sensitivity in the logistic regression model. Therefore, we
      would recommend the last method for determining the sensitivity and specificity
      of the APHABu.

PMID- 28756573
TI  - Classification of Culturable Bifidobacterial Population from Colonic Samples of
      Wild Pigs (Sus scrofa) Based on Three Molecular Genetic Methods.
AB  - Occurrence of bifidobacteria, known as health-promoting probiotic microorganisms,
      in the digestive tract of wild pigs (Sus scrofa) has not been examined yet. One
      hundred forty-nine fructose-6-phosphate phosphoketolase positive bacterial
      strains were isolated from colonic content of twenty-two individuals of wild pigs
      originated from four localities in the Czechia. Based on PCR-DGGE technique
      targeting the variable V3 region of the 16S rRNA genes, strains were initially
      differentiated into four groups represented by: (i) probably a new
      Bifidobacterium species (89 strains), (ii) B. boum/B. thermophilum/B.
      thermacidophilum subsp. porcinum/B. thermacidophilum subsp. thermacidophilum
      (sub)species (49 strains), (iii) Pseudoscardovia suis (7 strains), and (iv) B.
      pseudolongum subsp. globosum/B. pseudolongum subsp. pseudolongum (4 strains),
      respectively. Given the fact that DGGE technique did not allow to differentiate
      the representatives of thermophilic bifidobacteria and B. pseudolongum
      subspecies, strains were further classified by the 16S rRNA and thrS gene
      sequences. Primers targeting the variable regions of the latter gene were
      designed to be applicable in identification and phylogeny of Bifidobacteriaceae
      family. The 16S rRNA-derived phylogenetic study classified members of the first
      group into five subgroups in a separated cluster of thermophilic bifidobacteria.
      Comparable results were obtained by the thrS-derived phylogenetic analysis.
      Remarkably, variability among thrS sequences was higher compared with 16S rRNA
      gene sequences. Overall, molecular genetic techniques application allowed to
      identify a new Bifidobacterium phylotype which is predominant in the digestive
      tract of examined wild pigs.

PMID- 28756575
TI  - Evaluating the Safety of Medication Exposures During Pregnancy: A Case Study of
      Study Designs and Data Sources in Multiple Sclerosis.
AB  - BACKGROUND: Regulatory agencies often request prospective, product-specific post
      authorization pregnancy exposure registries to monitor safety during pregnancy,
      even though studies using existing health databases could also be employed.
      OBJECTIVES: Using multiple sclerosis (MS) as a case study, we evaluated various
      study designs and data sources previously used to study medication exposure in
      pregnancy. METHODS: We examined (1) strengths and limitations of study designs
      used for pregnancy safety studies in women exposed to MS-specific medications
      during pregnancy and (2) existing data sources used to conduct such studies in
      other disease areas. For the data sources identified, we contacted data
      custodians to determine the feasibility of assessing the risk of adverse outcomes
      in women with MS exposed to disease-modifying therapies (DMTs) during pregnancy.
      RESULTS: Of 43 MS-specific studies identified, most of which were prospective
      registries, very few, regardless of design and study population, produced timely
      and robust results for spontaneous abortions and major congenital malformations,
      considering study duration, achievement of target enrollment numbers, inclusion
      of internal comparators, and publication of results. Building on the successful
      use of existing healthcare databases to investigate drug safety during pregnancy
      in other disease areas, we identified 13 data sources that could be used to study
      intravenous DMT exposures in women with MS. CONCLUSIONS: Prospective, treatment
      specific registries have generally failed to deliver robust information. For this
      reason, other study approaches, in particular cohort studies using existing
      healthcare databases, should be considered for evaluating the safety of drug
      exposure in pregnancy, including in MS.

PMID- 28756574
TI  - Impact of prenatal stress on the dyadic behavior of mothers and their 6-month-old
      infants during a play situation: role of different dimensions of stress.
AB  - Prenatal stress (PS) is an established risk factor in the etiology of mental
      disorders. Although mother-child interaction is the infant's first important
      training in dealing with stress, little is yet known about the impact of PS on
      mother-infant dyadic behavior. The current study aimed to elucidate the
      prospective influence of psychological and physiological stresses during
      pregnancy on mother-infant dyadic behavior. Mother-infant interactions were
      videotaped at 6-month postpartum and coded into three dyadic patterns: (1) both
      positive; (2) infant protesting-mother positive; and (3) infant protesting-mother
      negative, using the infant and caregiver engagement phases. Exposure to PS was
      assessed during pregnancy using psychological (i.e., psychopathological,
      perceived, and psychosocial PS; n = 164) and physiological stress measures (i.e.,
      maternal cortisol; n = 134). Group comparisons showed that psychosocial PS was
      predictive of mother-infant behavior at 6-month postpartum, indicating that dyads
      of prenatally high-stressed mothers exhibited significantly more positive
      interaction patterns (i.e., infant positive-mother positive) as compared to the
      prenatally low-stressed group. Physiological PS was unrelated to mother-infant
      behavior. These results suggest that mild psychosocial PS may be advantageous for
      positive mother-infant dyadic behavior, which is in accordance with the stress
      inoculation model that assumes a beneficial effect of PS.

PMID- 28756576
TI  - Atypical Leber's hereditary optic neuropathy in a 10-year-old male: a case
      report.

PMID- 28756578
TI  - Design and application of a medication assessment tool for secondary prevention
      of stroke.
AB  - Background Optimisation of drug therapy is essential in the care of older persons
      and may be facilitated by application of medication assessment tools (MATs).
      Objective To design, psychometrically evaluate and apply an innovative MAT for
      secondary prevention of ischaemic stroke with particular relevance to older
      persons. Method Review criteria were selected from clinical practice guidelines
      and MAT-CVA was developed, validated and tested for reliability and feasibility.
      MAT-CVA was applied to 150 patients with a diagnosis of ischaemic stroke or
      transient ischaemic attack admitted to a rehabilitation hospital. Results MAT-CVA
      consists of 17 criteria sectioned into antithrombotic, lipid lowering,
      antihypertensive and glycaemic therapy. Content validity was demonstrated for all
      criteria. Reliability was confirmed with kappa values of 0.80 for both inter- and
      intraobserver agreements. Mean application time for the two observers was 5.55
      and 6.56 min. Adherence to applicable criteria was 55% and justified non
      adherence was 22.3%. Non-adherence was predominantly evident for prescription of
      anticoagulation in concurrent atrial fibrillation (36.4%), thiazide diuretics +/-
      angiotensin converting enzyme inhibitors for hypertension (26.8%) and
      dipyridamole at the recommended dose (24.0%). Conclusion Application of MAT-CVA
      indicated good overall adherence and identified gaps in clinical performance
      which may be targeted to enhance drug therapy optimisation.

PMID- 28756577
TI  - Omega-3 fatty acids revert high-fat diet-induced neuroinflammation but not
      recognition memory impairment in rats.
AB  - Neuroinflammation is a consequence of overeating and may predispose to the
      development of cognitive decline and neurological disorders. This study aimed to
      evaluate the impact of omega-3 supplementation on memory and neuroinflammatory
      markers in rats fed a high-fat diet. Male Wistar rats were divided into four
      groups: standard diet (SD); standard diet + omega-3 (SD + O); high fat diet
      (HFD); and high fat diet + omega-3 (HFD + O). Diet administration was performed
      for 20 weeks and omega-3 supplementation started at the 16th week. HFD
      significantly increased body weight, while omega-3 supplementation did not modify
      the total weight gain. However, animals from the HFD + O group showed a lower
      level of visceral fat along with an improvement in insulin sensitivity following
      HFD. Thus, our results demonstrate a beneficial metabolic role of omega-3
      following HFD. On the other hand, HFD animals presented an impairment in object
      recognition memory, which was not recovered by omega-3. In addition, there was an
      increase in GFAP-positive cells in the cerebral cortex of the HFD group, showing
      that omega-3 supplementation can be effective to decrease astrogliosis. However,
      no differences in GFAP number of cells were found in the hippocampus. We also
      demonstrated a significant increase in gene expression of pro-inflammatory
      cytokines IL-6 and TNF-alpha in cerebral cortex of the HFD group, reinforcing the
      anti-inflammatory role of this family of fatty acids. In summary, omega-3
      supplementation was not sufficient to reverse the memory deficit caused by HFD,
      although it played an important role in reducing the neuroinflammatory profile.
      Therefore, omega-3 fatty acids may play an important role in the central nervous
      system, preventing the progression of neuroinflammation in obesity.

PMID- 28756579
TI  - Evaluation of effects of an operational multidisciplinary team on antibiotic use
      in the medium to long term at a French university hospital.
AB  - Background Antibiotic-resistant bacteria are a major public health problem
      throughout the world. In 2006, in accordance with the national guidelines for
      antibiotic use, the CHRU of Nancy created an operational multidisciplinary
      antibiotic team at one of its sites. In 2011, a cluster-controlled trial showed
      that the operational multidisciplinary antibiotic team (the intervention) had a
      favourable short-term effect on antibiotic use and costs. Objective Our objective
      was to determine whether these effects continued over the medium to long term
      (that is, 2-7 years after creation of the operational multidisciplinary
      antibiotic team, 2009-2014). Setting The 1800-bed University Hospital of Nancy
      (France). Method The effect in the medium to long term is measured according to
      the same criteria and assessed by the same methods as the first study. A cluster
      controlled trial was performed on the period 2009-2014. The intervention group
      comprised 11 medical and surgical wards in settings where the operational
      multidisciplinary antibiotic team was implemented and the control group comprised
      6 wards without this operational team. Main outcome measure Consumption of
      antibiotics overall and by therapeutic class (in defined daily doses per 1000
      patient-days) and costs savings (in ?). Results The reduction in antibiotic use
      and costs continued, but at a lower rate than in the short term (11% between 2009
      and 2014 compared with 33% between 2007 and 2009) at the site of the
      intervention. The principal decreases concerned fluoroquinolones and
      glycopeptides. At the site without an operational multidisciplinary antibiotic
      team (the control group), total antibiotic use remained stable. Between 2009 and
      2014, costs fell 10.5% in the intervention group and 5.7% in the control group.
      Conclusion This study shows that it is possible to maintain the effectiveness
      over time of such an intervention and demonstrates its role in defining a
      hospital's antibiotic policy.

PMID- 28756580
TI  - Assessment of patients' knowledge and practices regarding their medication use
      and risks in Lebanon.
AB  - Background Patients' knowledge of their medications play a pivotal role in their
      disease management. Objective Assess the knowledge and practices of Lebanese
      outpatients regarding their own medication use and risks. Setting Four hundred
      and sixty community pharmacies across Lebanon. Method It was a cross-sectional
      study performed from March through May 2016 among Lebanese outpatients, using a
      self-administered questionnaire. Descriptive statistics were used to calculate
      all participants' responses. The association between categorical variables were
      evaluated using Pearson chi2 test or Fisher's exact test. Binary logistic
      regressions were performed to identify factors associated with medication
      patients' knowledge and interest. Main outcome measure Ability of the patients to
      identify own medications' elements: name, strength, dosage regimen, indication,
      and adverse drug reactions. Results Our study comprised 921 patients, with around
      16% taking >=5 medications/day. Around 56% of our patients showed sub-optimal
      medication knowledge. Patients' higher educational level, number of chronic
      diseases, and patient physician interaction were associated with higher
      medication knowledge. Many patients admitted not discussing their medications
      each time they visit their physicians (38.7%); not reading the leaflet of each
      medication they take (61.2%); and not regularly asking their pharmacist about the
      potential interactions of OTC drugs with prescribed medications (53.9%).
      Conclusion This study showed suboptimal medication-related knowledge, and
      suboptimal patient's interactions with primary care givers. Our findings serve as
      a platform for healthcare providers to understand patients' needs and educate
      them about medication use and risks.

PMID- 28756581
TI  - Predelivery uterine arteries embolization in patients affected by placental
      implant anomalies.
AB  - PURPOSE: The aim of this study is to report on a single center experience of
      managing patients affected by placenta previa major and/or accretism by
      embolizing uterine arteries immediately before the cesarean delivery to reduce
      blood loss and secondary the rate of hysterectomies. MATERIALS AND METHODS: Sixty
      nine patients have been prospectively enrolled. Inclusion criteria were
      radiological diagnosis of placenta anomalies and risk factors for peri/postpartum
      hemorrhage. The delivery was electively scheduled between the 35th week and the
      36th week of pregnancy. The embolization procedure was performed in the
      gynecological operating room with a mobile C-arm by injecting calibrated
      microparticles 500-700 MUm. A contrast-enhanced MRI was acquired in a subgroup of
      10 patients 6 months after the delivery to evaluate the uterine wall status.
      RESULTS: Hysterectomy had been performed in 43.5%; 52.2% did not require blood
      transfusions; 1.2 blood units per patient had been meanly transfused. The mean
      fluoroscopy beam-on time was 195 s per patient. The mean uterine dose was 26.75
      mGy. No pH anomalies were measured from the umbilical cord blood; the Apgar score
      at 5 min was >=8. The analysis of the neuro-developmental milestones showed
      normal cognitive development in all children at 6 months. The uterine wall
      enhancement evaluated with contrast-enhanced MRI 6 months after the embolization
      procedure showed preserved myometrial perfusion without area of necrosis.
      CONCLUSIONS: In this series of patients, the predelivery uterine arteries'
      embolization was a safe and effective procedure; this may represent a technical
      alternative that interventional radiologists can consider when facing this
      challenging scenario.

PMID- 28756582
TI  - RNAi-mediated SMV P3 cistron silencing confers significantly enhanced resistance
      to multiple Potyvirus strains and isolates in transgenic soybean.
AB  - KEY MESSAGE: Robust RNAi-mediated resistance to multiple Potyvirus strains and
      isolates, but not to Secovirus BPMV, was conferred by expressing a short SMV P3
      hairpin in soybean plants. Engineering resistance to multiple Potyvirus strains
      is of great interest because of a wide variability of the virus strains, and
      mixed infections of multiple viruses or strains commonly associated with field
      grown soybean. In this study, RNAi-mediated silencing of the soybean mosaic virus
      (SMV) P3 cistron, which is reported to participate in virus movements and
      pathogenesis and to be the putative determinant of SMV virulence, was used to
      induce resistance to multiple Potyvirus strains and isolates in soybean. A 302 bp
      inverted repeat (IR) of the P3 cistron, isolated from the SMV strain SC3, was
      introduced into soybean. The transgenic lines exhibited stable and enhanced
      resistance to SMV SC3 under field conditions over 3 consecutive years. The
      transgenic lines also showed significantly enhanced resistance to four other SMV
      strains (SC7, SC15, SC18, and SMV-R, a novel recombinant found in China), the
      soybean-infecting bean common mosaic virus (BCMV) and watermelon mosaic virus
      (WMV). Nevertheless, no significant differences were found between transgenic
      plants and their non-transformed (NT) counterparts in terms of resistance to bean
      pod mottle virus (BPMV, Secoviridae). Consistent with the results of resistance
      evaluations, the expression of the respective viral CP cistrons and virus
      accumulation were significantly lower in seven Potyvirus strains and isolates
      than in the NT plants, but not in BCMV-inoculated transgenic lines. The results
      demonstrate the effectiveness of engineering resistance to multiple Potyvirus
      strains and isolates via RNAi-mediated SMV P3 cistron silencing, and thus provide
      an effective control strategy against Potyvirus infections in soybean and other
      crops.

PMID- 28756583
TI  - Phytopathogen-induced changes to plant methylomes.
AB  - DNA methylation is a dynamic and reversible type of epigenetic mark that
      contributes to cellular physiology by affecting transcription activity,
      transposon mobility and genome stability. When plants are infected with
      pathogens, plant DNA methylation patterns can change, indicating an epigenetic
      interplay between plant host and pathogen. In most cases methylation can change
      susceptibility. While DNA hypomethylation appears to be a common phenomenon
      during the susceptible interaction, the levels and patterns of hypomethylation in
      transposable elements and genic regions may mediate distinct responses against
      various plant pathogens. The effect of DNA methylation on the plant immune
      response and other cellular activities and molecular functions is established by
      localized differential DNA methylation via cis-regulatory mechanisms as well as
      through trans-acting mechanisms. Understanding the epigenetic differences that
      control the phenotypic variations between susceptible and resistant interactions
      should facilitate the identification of new sources of resistance mediated by
      epigenetic mechanisms, which can be exploited to endow pathogen resistance to
      crops.

PMID- 28756585
TI  - Response concerning 'Letter to editor' by Ni et al. (2017), Arch Orthop Trauma
      Surg. DOI 10.1007/s00402-017-2710-2.

PMID- 28756584
TI  - Estimated Healthcare Costs of Melanoma in Australia Over 3 Years Post-Diagnosis.
AB  - BACKGROUND: Skin cancer exerts a large and growing burden on health systems. With
      new pharmacotherapies for metastatic melanoma now available, a contemporary
      understanding of the cost burden of melanoma control is warranted. OBJECTIVE: To
      comprehensively assess the healthcare costs of malignant melanoma diagnosis and
      treatment in Australia, over 3 years after diagnosis. METHODS: We developed a
      decision-analytic model and micro-costing method to estimate the mean cost per
      patient for melanoma, incorporating all diagnostic and treatment modalities used
      in Australia (2017 AU$). By using the de-identified 10% sample of Medicare
      Benefits Scheme, we analysed health service use and supplemented our analyses
      with published estimates. We took a health system cost perspective, and addressed
      input uncertainty with sensitivity analyses. RESULTS: The mean annual cost per
      patient for melanoma stage 0/I/II was AU$1681 (US$1175) rising to AU$37,729
      (US$26,365) for stage III resectable, and AU$115,109 (US$80,440) for stage III
      unresectable/IV. Three-year costs for stage III unresectable/IV were AU$187,720.
      Nationally, the annual estimated cost for treatment of all new cases of in situ
      and invasive melanomas was AU$201 million (95% CI: AU$187 to AU$216 million).
      When we included treatments for presumptive melanoma later found to be benign
      lesions, the estimated annual cost burden reached AU$272 million. CONCLUSION:
      With rapidly rising treatment costs, there is a need to consider a comprehensive
      melanoma control strategy that includes primary prevention of skin cancers and
      cost-effective sun protection initiatives.

PMID- 28756586
TI  - The female geriatric proximal humeral fracture: protagonist for straight
      antegrade nailing?
AB  - INTRODUCTION: Straight antegrade humeral nailing (SAHN) has become a standard
      technique for the surgical fixation of proximal humeral fractures, which
      predominantly affect elderly females. The nail's proximal anchoring point has
      been demonstrated to be critical to ensure reliable fixation in osteoporotic bone
      and to prevent iatrogenic damage to the superior rotator cuff bony insertion.
      Anatomical variations of the proximal humerus, however, may preclude satisfactory
      anchoring of the nail's proximal end and may bare the risk of rotator cuff
      violation, even though the nail is inserted as recommended. The aim of this study
      was to evaluate the anatomical suitability of proximal humeri of geriatric
      females aged 75 years and older for SAHN. Specifically, we sought to assess the
      proportion of humeri not anatomically amenable to SAHN for proximal humeral
      fracture. MATERIALS AND METHODS: A total of 303 proximal humeri of 241 females
      aged 75 years and older (mean age 84.5 +/- 5.0 years; range 75-102 years) were
      analyzed for this study. Multiplanar two-dimensional reformations (true ap, true
      lateral, and axial) were reconstructed from shoulder computed tomography (CT)
      data sets. The straight antegrade nail's ideal entry point, "critical point"
      (CP), and critical distance (CD; distance between ideal entry point and CP) were
      determined. The rate of proximal humeri not anatomically suitable for SAHN
      (critical type) was assessed regarding proximal reaming diameters of currently
      available straight antegrade humeral nails. RESULTS: Overall, 35.6% (108/303) of
      all proximal humeri were found to be "critical types" (CD <8 mm) as to the
      recommended minimal proximal reaming diameter of 10 mm of straight antegrade
      nails currently in use. Moreover, 43.2% (131/303) of the humeri were considered
      "critical types" with regard to the alternatively used larger proximal reaming
      diameter of 11.5 mm. Mean CD was 9.0 +/- 1.7 mm (range 3.5-13.5 mm) and did not
      correlate with age (r = -0.04, P = 0.54). No significant differences in CD and
      rate of "critical types" were found between left and right humeri as well as
      between females aged between 75 and 84 years (n = 151) and females aged 85 and
      older (n = 152). CONCLUSIONS: More than a third of proximal humeri of geriatric
      females are "critical types" as to SAHN and may, therefore, be at risk for
      procedure-related complications, such as rotator cuff violation, fixation
      failure, and potential malreduction. In view of this finding, we recommend to
      routinely analyze multiplanar CT reformations of the uninjured contralateral side
      prior to surgery to improve selection of patients for SAHN and to minimize
      foreseeable complications. For "critical type" humeri, an alternative surgical
      procedure should be considered.

PMID- 28756587
TI  - Phenotyping first-generation genome editing mutants: a new standard?
AB  - The unprecedented efficiency of the CRISPR/Cas9 system in genome engineering has
      opened the prospect of employing mutant founders for phenotyping cohorts, thus
      accelerating research projects by circumventing the requirement to generate
      cohorts using conventional two- or three-generation crosses. However, these first
      generation mutants are often genetic mosaics, with a complex and difficult to
      define genetic make-up. Here, we discuss the potential benefits, challenges and
      scientific validity of such models.

PMID- 28756588
TI  - Trace element concentrations in livers of Common Buzzards Buteo buteo from
      eastern Poland.
AB  - In this study, our aim was to determine the common sources of origin of 18
      elements in the livers of Common Buzzards collected during the breeding season in
      an extensive agricultural landscape in south-east Poland with respect to age
      (adults and immatures) and sex (males and females). In all 34 specimens
      collected, the element concentrations followed the pattern of S > Na > Fe > Mg >
      Zn > Si > Cu > Mn > Ba > Se > B > Pb > Hg > Cd > Cr > Ni > Sr > V. Among the
      heavy metals examined, only the concentration of Pb was relatively high. Given
      the prevalence of farmland in the studied area (and the wide use of fertilizers),
      common use of lead-hunting ammunition and moderate concentration of Pb in
      fertilizers, the indirect influence of hunting ammunition ingested with food or
      as gastroliths was apparently responsible for the elevated levels of Pb in the
      livers of Common Buzzards. In our study, no significant sex-related differences
      were detected in the hepatic concentrations of any element. However, a
      significant age effect was observed for three elements, which had elevated levels
      in adults (Hg) and immature birds (B, Pb), and a significant age x sex
      interaction was found for S and Fe. These results might be explained by the
      importance of these elements in bone growth in immature birds (B), variable
      strategies of foraging between adults and immature birds (Pb), and possible
      intersex differences in the immature cohort in response to the presence of lead
      (S, Fe).

PMID- 28756589
TI  - Crosstalk between the angiotensin and endothelin system in the cerebrovasculature
      after experimental induced subarachnoid hemorrhage.
AB  - Under physiologic conditions, losartan showed a dose-dependent antagonistic
      effect to the endothelin-1 (ET-1)-mediated vasoconstriction. This reduced
      vasoconstriction was abolished after preincubation with an endothelin B1 receptor
      (ET(B1)-receptor) antagonist. Also, an increased ET(B1)-receptor-dependent
      relaxation to sarafotoxin S6c (S6c; an ET(B1)-receptor agonist) was detected by
      preincubation with losartan. Investigations after experimental induced
      subarachnoid hemorrhage (SAH) are still missing. Therefore, we analyzed losartan
      in a further pathological setup. Cerebral vasospasm was induced by a modified
      double hemorrhage model. Rats were sacrificed on day 3 and isometric force of
      basilar artery ring segments was measured. Parallel to physiological conditions,
      after SAH, the ET-1-induced vasoconstriction was decreased by preincubation with
      losartan. This reduced contraction has been abolished after preincubation with BQ
      788, an ET(B1)-receptor antagonist. In precontracted vessels, ET-1 induced a
      higher vasorelaxation under losartan and the endothelin A receptor (ET(A)
      receptor) antagonist BQ-123. After SAH, losartan caused a modulatory effect on
      the ET(B1)-receptor-dependent vasorelaxation. It further induced an upregulation
      of the NO pathway. Under losartan, the formerly known loss of the ET(B1)-receptor
      vasomotor function was abolished and a significantly increased relaxation,
      accompanied with an enhanced sensitivity of the ET(B1)-receptor, has been
      detected. Also, the dose-dependent antagonistic effect to the ET-1-induced
      contraction can be effected by angiotensin II type 1 receptor (AT1-receptor)
      antagonism due to losartan directly via the ET(B1)-receptor.

PMID- 28756590
TI  - Improved fermentative L-cysteine overproduction by enhancing a newly identified
      thiosulfate assimilation pathway in Escherichia coli.
AB  - Sulfate (SO42-) is an often-utilized and well-understood inorganic sulfur source
      in microorganism culture. Recently, another inorganic sulfur source, thiosulfate
      (S2O32-), was proposed to be more advantageous in microbial growth and
      biotechnological applications. Although its assimilation pathway is known to
      depend on O-acetyl-L-serine sulfhydrylase B (CysM in Escherichia coli), its
      metabolism has not been extensively investigated. Therefore, we aimed to explore
      another yet-unidentified CysM-independent thiosulfate assimilation pathway in E.
      coli. DeltacysM cells could accumulate essential L-cysteine from thiosulfate as
      the sole sulfur source and could grow, albeit slowly, demonstrating that a CysM
      independent thiosulfate assimilation pathway is present in E. coli. This pathway
      is expected to consist of the initial part of the thiosulfate to sulfite (SO32-)
      conversion, and the latter part might be shared with the final part of the known
      sulfate assimilation pathway [sulfite -> sulfide (S2-) -> L-cysteine]. This is
      because thiosulfate-grown DeltacysM cells could accumulate a level of sulfite and
      sulfide equivalent to that of wild-type cells. The catalysis of thiosulfate to
      sulfite is at least partly mediated by thiosulfate sulfurtransferase (GlpE),
      because its overexpression could enhance cellular thiosulfate sulfurtransferase
      activity in vitro and complement the slow-growth phenotype of thiosulfate-grown
      DeltacysM cells in vivo. GlpE is therefore concluded to function in the novel
      CysM-independent thiosulfate assimilation pathway by catalyzing thiosulfate to
      sulfite. We applied this insight to L-cysteine overproduction in E. coli and
      succeeded in enhancing it by GlpE overexpression in media containing glucose or
      glycerol as the main carbon source, by up to ~1.7-fold (1207 mg/l) or ~1.5-fold
      (1529 mg/l), respectively.

PMID- 28756591
TI  - Disinfection of bacteriophage MS2 by copper in water.
AB  - Households that lack piped water supply are often forced to meet water needs by
      storing in the home, leaving water vulnerable to contamination by viruses.
      Storage in copper containers can potentially prevent this type of contamination,
      but the inactivation kinetics of viruses by copper need to be described to make
      appropriate storage recommendations. This work characterized inactivation
      kinetics of bacteriophage MS2 as a surrogate for enteric viruses by dissolved
      ionic copper in water. Reduction of MS2 increased with increasing doses of
      copper. At 0.3 mg/L, there was a 1.8-log10 reduction of MS2 within 6 h. At 1 and
      3 mg/L, 2-2.5 log10 inactivation could be achieved between 6 and 24 h. Parameters
      for the Chick-Watson, Hom, and One Hit-Two Population models of inactivation were
      calculated and evaluated, all of which demonstrated strong goodness-of-fit and
      predictability at various contact times. Copper inactivates MS2 under controlled
      conditions at doses between 0.3 and 3 mg/L. Although requiring longer contact
      times than conventional disinfectants, it is a candidate for improving the safety
      of stored drinking water.

PMID- 28756592
TI  - Evaluating the potential of circulating hTERT levels in glioma: can plasma levels
      serve as an independent prognostic marker?
AB  - Glioma is an aggressive primary Neuro-epithelial tumor with dismal prognosis,
      since there is a lack of molecular work-up during routine radiological monitoring
      of the disease. Currently, a number of potential molecular prognostic and
      predictive biomarkers are being characterized in line with structured diagnosis
      defined in World Health Organization guidelines 2016. Human-telomerase reverse
      transcriptase (hTERT), a marker of proliferation and maintenance of genomic
      integrity has thus been investigated for its clinical relevance as an independent
      prognosticator in glioma. Expression of the protein in tumor tissue and in plasma
      of 72 diffuse glioma patients (astrocytoma) grade II-IV was determined and
      compared with relevant controls using immunofluorescence-immunohistochemistry and
      enzyme-linked immuno-sorbent assay. Appropriate statistical tests were applied to
      establish a correlation between on-site tumor and circulating levels of the
      marker and its independence of covariates. Expression of the marker in glioma
      tissues was significantly different from controls (p < 0.0001) and could
      discriminate within grades with >=80% sensitivity. The tissue and plasma levels
      were positively associated with grades (r = 0.8845, p < 0.0001) and (r = 0.2834,
      p = 0.0158) respectively, while an inverse correlation with overall survival (r =
      -0.6558, p < 0.0001) and (r = -0.3941, p = 0.0006) respectively, was recorded.
      Plasma hTERT was significantly correlated with corresponding intra-tumor
      expression of hTERT (r = 0.2794, p = 0.0175). Multivariate Cox-regression
      identified plasma hTERT (p < 0.0005) as a prognostic factor; not associated with
      age, site or extent of resection (p > 0.05). This is the first experimental
      evidence for association of higher plasma levels of hTERT with overall survival
      in both low and high grade glioma.

PMID- 28756593
TI  - Serial changes in lymphocyte subsets in patients with newly diagnosed high grade
      astrocytomas treated with standard radiation and temozolomide.
AB  - The immune system plays a significant role in cancer prevention and outcome. In
      high grade astrocytomas (HGA), severe lymphopenia is associated with shortened
      survival due to tumor progression. This study was performed to quantify serial
      changes in lymphocyte subsets in HGA following standard radiation (RT) and
      temozolomide (TMZ). Adults (KPS >60, HIV negative) with newly diagnosed HGA
      scheduled to receive concurrent RT and TMZ and adjuvant TMZ were eligible. Blood
      was collected before beginning concurrent RT/TMZ and at weeks 6, 10, 18, and 26,
      and 3 months after completing adjuvant TMZ. Lymphocyte subsets were analyzed by
      flow cytometry. Twenty patients (70% glioblastoma, median age 53, 50% male, 80%
      Caucasian) who enrolled from January 2014 to August 2014 were followed until
      April 2016. Baseline dexamethasone dose was 0.5 mg/day and 15% had absolute
      lymphocyte counts (ALC) <1000 cells/mm3 before starting RT/TMZ. However, 75%
      developed lymphopenia with ALC <1000 cells/mm3 after completion of RT/TMZ. NK
      cells, B cells and all T lymphocytes subsets dropped significantly after
      concurrent RT/TMZ and remained depressed for the 48 weeks of observation. The
      CD4+/CD8+ ratio was not affected significantly during follow-up. Severe
      lymphopenia involving all subsets occurred early in treatment and remained
      present for nearly 1 year. To our knowledge, this is the first report of serial
      trends in lymphocyte subsets following standard RT and TMZ for HGA.

PMID- 28756594
TI  - Decreased acute toxicities of intensity-modulated radiation therapy for localized
      prostate cancer with prostate-based versus bone-based image guidance.
AB  - BACKGROUND: Intensity-modulated radiation therapy (IMRT) is a major therapeutic
      option for localized prostate cancer. Image-guided radiation therapy (IGRT)
      allows tumor visualization and corrects the errors caused by daily internal
      movement of the prostate. The current study retrospectively compared the acute
      toxicities and biochemical tumor control outcomes of prostate IMRT achieved using
      two IGRT techniques: bony structure-based IGRT (B-IGRT) and prostate-based IGRT
      (P-IGRT). METHODS: Between February 2011 and July 2014, 96 patients with low- or
      intermediate-risk prostate cancer were treated using P-IGRT based on cone-beam
      computed tomography (CBCT; 76 Gy) without fiducial markers. This group of
      patients was compared with a similar cohort of 96 patients who were treated with
      B-IGRT (74 Gy) between July 2007 and September 2011. The planning target volume
      (PTV) margins were 1-3 mm smaller in the P-IGRT group than in the B-IGRT group.
      RESULTS: The median follow-up periods for all patients, the P-IGRT group, and the
      B-IGRT group were 42, 32, and 64 months, respectively. A significantly lower
      incidence of acute grade 2 or higher gastrointestinal toxicities was observed in
      the P-IGRT group compared with the B-IGRT group (3 vs. 11%; p = 0.049). The
      prostate-specific antigen failure-free survival rates at 3 years were 95.5 and
      92.7% for the P-IGRT and B-IGRT groups, respectively (p = 0.534). CONCLUSIONS:
      IMRT with P-IGRT allows PTV margin reduction without sacrificing tumor control,
      which successfully reduces acute rectal toxicity compared with IMRT with B-IGRT.

PMID- 28756595
TI  - Structural and functional assessment after intravitreal injection of ranibizumab
      in diabetic macular edema.
AB  - PURPOSE: To evaluate structure and function improvement in central retina by
      optical coherence tomography (OCT) and multifocal electroretinography (mf-ERG) in
      diabetic macular edema (DME) patients after intravitreal injection of ranibizumab
      (IVR) treatment. METHODS: Twenty-seven eyes in 27 patients with DME received
      three consecutive monthly injections of IVR (0.05 ml, 10 mg/ml) and as needed
      thereafter. The clinical parameters of best-corrected visual acuity (BCVA),
      central foveal thickness (CFT) and mf-ERG were monitored for 6 months before and
      after IVR. The findings at baseline, 1, 3 and 6 months were analyzed. Correlation
      and regression analyses were performed on BCVA, CFT, mf-ERG amplitude and
      implicit time of the N1 and P1 waves. RESULTS: IVR significantly improved visual
      acuity from the beginning of the treatment (P < 0.05). There were significant
      decreases in the CFT compared with the baseline after IVR (P < 0.05). The mean
      amplitude of P1 and N1 in the central ring at all examinations increased
      significantly compared with the baseline (P < 0.05). The mean P1 and N1 implicit
      times in the central ring were shortened, but not significantly (P > 0.05). There
      were significant correlations of BCVA with CFT, P1 and N1 amplitudes in the
      central retina (P < 0.05). CONCLUSION: In addition to the improvement in BCVA and
      the reduction in CFT, IVR improved macular retinal function, as assessed by mf
      ERG, in diabetic eyes. The combination of OCT and mf-ERG for macular evaluation
      may better assess DME.

PMID- 28756596
TI  - New photic stimulating system with white light-emitting diodes to elicit
      electroretinograms from zebrafish larvae.
AB  - PURPOSE: The zebrafish is an established animal model commonly used in
      biological, neuroscience, and genetic research. We have developed a new light
      stimulating system using white light-emitting diodes (LEDs) to elicit ERGs from
      zebrafish larvae. The purpose of this study was to record full-field ERGs and to
      evaluate the inter-trial reliability of the ERGs recorded with our system from
      zebrafish larvae. METHODS: The stimulating device used white LEDs that were
      attached to a stereomicroscope, and the location of the recording electrode on
      the cornea could be monitored while the eye was being stimulated. Full-field
      scotopic and photopic ERGs were recorded from larvae at the age of 5-7 days post
      fertilization (dpf). Intensity-response curves were constructed from the ERGs.
      Inter-trial reliability of the ERGs recorded by our system was evaluated.
      RESULTS: This stimulating system could be used for efficient and reliable ERG
      recordings from 5-7 dpf larvae. The amplitudes, implicit times, and the waveforms
      of the scotopic and photopic ERGs were similar to those reported in earlier
      studies. Inter-trial reliability of the amplitudes of the photopic ERG b-waves
      was excellent with an intra-class correlation coefficient of 0.98. CONCLUSION: We
      conclude that this new light stimulation system using white LEDs attached to a
      stereomicroscope will be helpful in recording reliable ERGs from zebrafish
      larvae.

PMID- 28756599
TI  - Long-term monitoring of intracranial pressure in normal pressure hydrocephalus
      and other CSF disorders.
AB  - Long-term monitoring of intracranial pressure is a useful method in the diagnosis
      of complex hydrocephalus and CSF disorders. This editorial discusses various
      criteria for the interpretation of ICP monitoring in normal pressure
      hydrocephalus, idiopathic intracranial hypertension and in patients with
      implanted hydrocephalus shunts.

PMID- 28756598
TI  - Risk factors and predictors of mortality of candidaemia among critically ill
      patients: role of antifungal prophylaxis in its development and in selection of
      non-albicans species.
AB  - PURPOSE: The aim of the present study is to identify risk factors for development
      and predictors of mortality of candidaemia among critically ill patients.
      METHODS: A 1:7 case-control study was conducted during a 4-year period (2012
      2015) in a Greek Intensive Care Unit (ICU). Candidaemia was confirmed by positive
      blood cultures. All yeasts were identified using API 20C AUX System or Vitek 2
      Advanced Expert System. Epidemiologic data were collected from the ICU
      computerized database and patients' chart reviews. RESULTS: Fifty-three patients
      developed candidaemia with non-albicans species being the predominant ones (33
      patients, 62.3%). Multivariate analysis found that prior emergency surgery,
      malignancy, hospitalization during summer months, prior septic shock by KPC
      producing Klebsiella pneumoniae and number of antibiotics administered were
      independently associated with candidaemia, while, prior administration of azole
      was a protective factor. Non-albicans candidaemia was associated with number of
      antibiotics administered and prior administration of echinocandin. Mortality of
      14 days was 28.3% (15 patients) and was associated with SOFA score upon infection
      onset and septic shock, while, appropriate empirical antifungal treatment was
      associated with better survival. CONCLUSIONS: Prophylactic azole administration
      prevents development of candidaemia, while, echinocandin administration
      predisposes to non-albicans candidaemia. Empirical administration of an
      appropriate antifungal agent is associated with better survival.

PMID- 28756597
TI  - Treatments for Metastatic Prostate Cancer (mPC): A Review of Costing Evidence.
AB  - BACKGROUND: Prostate cancer (PC) is the most common cancer in Western countries.
      More than one third of PC patients develop metastatic disease, and the 5-year
      expected survival in distant disease is about 35%. During the last few years, new
      treatments have been launched for metastatic castrate-resistant prostate cancer
      (mCRPC). OBJECTIVES: We aimed to review the current literature on health economic
      analysis on the treatment of metastatic prostate cancer (mPC), compare the
      studies, summarize the findings and make the results available to administrators
      and decision makers. METHODS: A systematic literature search was done for
      economic evaluations (cost-minimization, cost-effectiveness, cost-utility, cost
      of-illness, cost-of-drug, and cost-benefit analyses). We employed the PubMed(r)
      search engine and searched for publications published between 2012 and 2016. The
      terms used were "prostate cancer", "metastatic" and "cost". An initial screening
      of all headlines was performed, selected abstracts were analysed, and finally the
      full papers investigated. Study characteristics, treatment and comparator,
      country, type of evaluation, perspective, year of value, time horizon, efficacy
      data, discount rate, total costs and sensitivity analysis were analysed. The
      quality was assessed using the Quality of Health Economic Studies (QHES)
      instrument. RESULTS: A total of 227 publications were detected and screened, 58
      selected for full-text assessment and 31 included in the final analyses. Despite
      the significant international literature on the treatment of mCRPC, there were
      only 15 studies focusing on cost-effectiveness analysis (CEA). Medical treatment
      constituted two thirds of the selected studies. Significant costs in the
      treatment of mCRPC were disclosed. In the pre-docetaxel setting, both abiraterone
      acetate (AA) and enzalutamide were concluded beyond accepted cost/quality
      adjusted life year limits. In the docetaxel refractory setting, most studies
      concluded that enzalutamide was cost-effective and superior to AA. In most
      studies, cabazitaxel was not recommended, because of high cost. Looking at bone
      targeting drugs, generic zoledronic acid (ZA) was recommended. External beam
      radiotherapy (EBRT) was analysed in three studies, and single fraction
      radiotherapy was concluded to be cost saving. Radium-223 was documented as
      beneficial, but costly. The quality of the studies was generally good, but
      sensitivity analyses, discounting and the measurement of health outcomes were
      present in less than two thirds of the selected studies. CONCLUSIONS: The
      treatment of mCRPC was associated with significant cost. In the post-docetaxel
      setting, single fraction radiotherapy and enzalutamide were considered cost
      effective in most studies. Generic ZA was the recommended bone-targeting therapy.

PMID- 28756600
TI  - Trace Metals in the Urine and Hair of a Population in an Endemic Arsenism Area.
AB  - There have been few investigations of trace elements in the urine and hair of
      populations exposed to high levels of arsenic (As) in drinking water. Therefore,
      concentrations of selected metals in urine and hair samples from a population in
      a study area where arsenism was endemic and a control area were determined. It
      was found that the median concentrations of barium (Ba), cadmium (Cd), cobalt
      (Co), chromium (Cr), copper (Cu), manganese (Mn), molybdenum (Mo), nickel (Ni),
      lead (Pb), zinc (Zn), and As in the urine samples from the population in the
      study area were 3.87, 0.47, 0.50, 61.84, 26.82, 1.33, 128.45, 7.05, 1.10, 233.75,
      and 339.63 MUg/L, respectively. The corresponding values in the urine samples
      from a population in the control area were 29.08, 0.19, 0.21, 27.77, 10.32, 4.61,
      14.01, 2.19, 3.90, 113.92, and 20.28 MUg/L, respectively. In the study area, Ba,
      Cd, Co, Cr, Cu, Mo, Ni, Pb, and Zn excreted in the urine were likely to be mainly
      derived from drinking water with high levels of arsenic. The median
      concentrations of Ba, Cd, Co, Cr, Cu, Mn, Mo, Ni, Pb, Zn, and As in the hair
      samples from the study area were 4.16, 0.03, 0.09, 1.09, 6.54, 1.97, 0.06, 0.53,
      1.64, 144.28, and 1.67 mg/kg, respectively. The corresponding values from the
      control area were 4.76, 0.03, 0.02, 1.41, 8.31, 1.34, 0.07, 0.39, 0.86, 154.58,
      and 0.29 mg/kg, respectively. Significant positive correlations were observed
      between As and Ba, Cd, Co, Cr, Cu, Mo, Ni, Pb, and Zn in the urine in the study
      area. However, As was not positively associated with these metals in the hair
      samples. Exposure to high levels of As in drinking water increased the
      accumulation of Ba and Mn in the hair and the excretion of Cd, Cu, and Mo in the
      urine in the study area. The population in the study area might experience Cu and
      Mo deficiencies for an increasing excretion of Cu and Mo.

PMID- 28756601
TI  - Mechanistic insight into pyrene removal by natural sepiolites.
AB  - This paper investigates the sorption characteristics and mechanisms of pyrene
      onto two types of natural sepiolite-brown (B-Sep) and white (W-Sep). The effects
      of relevant properties such as clay content, surface area, pore diameter and
      volume, divalent cations, and organic carbon content were investigated by single
      component batch adsorption systems. The results suggest that pyrene has high
      affinity for both sepiolite and its sorption behavior could be mainly affected by
      exchangeable strongly hydrated cations such as Ca2+ and H2O in the zeolite-like
      channels and by open channel defects (OCD) structures but no so much by the large
      number of Si-OH groups located on the sepiolite's basal surfaces. Mesoporosity
      rather than surface area largely controls the sorption capacity and intensity of
      both sepiolites. This is shown by the increase in pore volume that exhibited the
      greatest increase in BET surface area. Particle size and morphological changes of
      both sepiolites following pyrene adsorption determined by FE-SEM showed that the
      sepiolite fibers are much longer than their widths, which are only several laths
      (several nanometers). This is a result of growth, mostly along the c-axis, at the
      expense of the diffusion of pyrene molecules through aqueous solution. As a
      consequence, a significant fibrous morphology is produced following the
      adsorption of pyrene by both sepiolites.

PMID- 28756604
TI  - Henri Meige (1866-1940).

PMID- 28756602
TI  - Anxiety-like behavioural effects of extremely low-frequency electromagnetic field
      in rats.
AB  - In recent years, extremely low-frequency electromagnetic field (ELF-EMF) has
      received considerable attention for its potential biological effects. Numerous
      studies have shown the role of ELF-EMF in behaviour modulation. The aim of this
      study was to investigate the effect of short-term ELF-EMF (50 Hz) in the
      development of anxiety-like behaviour in rats through change hypothalamic
      oxidative stress and NO. Ten adult male rats (Wistar albino) were divided in two
      groups: control group-without exposure to ELF-EMF and experimental group-exposed
      to ELF-EMF during 7 days. After the exposure, time open field test and elevated
      plus maze were used to evaluate the anxiety-like behaviour of rats. Upon
      completion of the behavioural tests, concentrations of superoxide anion (O2.-),
      nitrite (NO2-, as an indicator of NO) and peroxynitrite (ONOO-) were determined
      in the hypothalamus of the animals. Obtained results show that ELF-EMF both
      induces anxiety-like behaviour and increases concentrations of O2.- and NO,
      whereas it did not effect on ONOO- concentration in hypothalamus of rats. In
      conclusion, the development of anxiety-like behaviour is mediated by oxidative
      stress and increased NO concentration in hypothalamus of rats exposed to ELF-EMF
      during 7 days.

PMID- 28756605
TI  - Magnetic resonance imaging of leg muscles in patients with myotonic dystrophies.
AB  - Magnetic resonance imaging (MRI) of muscles has recently become a significant
      diagnostic procedure in neuromuscular disorders. There is a lack of muscle MRI
      studies in patients with myotonic dystrophy type 1 (DM1), especially type 2
      (DM2). To analyze fatty infiltration of leg muscles, using 3.0 T MRI in patients
      with genetically confirmed DM1 and DM2 with different disease durations. The
      study comprised 21 DM1 and 10 DM2 adult patients. Muscle MRI was performed in
      axial plane of the lower limbs using T1-weighted (T1w) sequence. Six-point scale
      by Mercuri et al. was used. Fatty infiltration registered in at least one muscle
      of lower extremities was found in 71% of DM1 and 40% of DM2 patients. In DM1
      patients, early involvement of the medial head of gastrocnemius and tibialis
      anterior muscles was observed with later involvement of other lower leg muscles
      and of anterior and posterior thigh compartments with relative sparing of the
      rectus femoris. In DM2, majority of patients had normal MRI findings. Early
      involvement of lower legs and posterior thighs was found in some patients. Less
      severe involvement of the medial head of the gastrocnemius compared to other
      lower leg muscles was also observed, while involvement of proximal muscles was
      rather diffuse than selective. It seems that both in DM1 and DM2 some muscles may
      be affected before weakness is clinically noted and vice versa. We described
      characteristic pattern and way of progression of muscle involvement in DM1 and
      DM2.

PMID- 28756606
TI  - A novel imaging technique for better detecting new lesions in multiple sclerosis.
AB  - We developed a tool that performs longitudinal subtraction of 3D double inversion
      recovery (DIR) images in follow-up magnetic resonance (MR) examinations of
      patients with multiple sclerosis. As DIR sequences show a high lesion-to
      parenchyma contrast, we hypothesized that such a tool might lead to increased
      sensitivity for new lesions as well as to speeding up the routine clinical work
      up of follow-up MR imaging in multiple sclerosis by directly visualizing new
      lesions. DIR subtraction images of serial MR examinations were calculated in 106
      patients with multiple sclerosis. Existence of new lesions was assessed in three
      different ways: by standard visual comparison, by FLAIR, and by DIR subtraction
      maps. A reference standard, to which the single modalities were compared, was
      defined by combining all information from all readouts and all readers. The
      presence and number of new lesions were determined and the time needed for
      analysis measured. Accuracy of detecting overall existence of new lesions using
      DIR subtraction maps was significantly higher than using visual comparison (96
      vs. 86%, p = 0.013) or FLAIR subtraction maps (p < 0.001), with increased
      sensitivity and higher negative predictive value. Significantly more new lesions
      were detected when using DIR subtraction maps (p < 0.001). Analyzing subtraction
      maps took less than a third of the time needed for the standard visual comparison
      (p = 0.007). Thus, DIR subtraction maps improve the detection of new lesions in a
      clinical setting both in terms of accuracy and in terms of speed.

PMID- 28756607
TI  - A Randomized, Open-Label, Two-Way Crossover, Single-Dose Bioequivalence Study of
      Temozolomide 200 mg/m2 (Dralitem(r) vs. Temodal(r) Capsules) in Patients with
      Primary Tumors of the Central Nervous System Under Fasting Conditions.
AB  - BACKGROUND: Temozolomide is an antineoplastic agent of proven efficacy against
      high-grade gliomas. PURPOSE: The objective of this crossover, single-dose,
      bioequivalence study was to compare the rate and extent of absorption of oral
      temozolomide after administration of the study product (Dralitem(r), Monte Verde
      Sociedad Anonima) and the reference product (Temodal(r), originator product
      manufactured by Schering Plough Laboratories) in patients with primary central
      nervous system (CNS) tumors under fasting conditions. METHODS: Sixteen male and
      female subjects with primary CNS tumors (excluding CNS lymphoma) were recruited,
      and were administered temozolomide 200 mg/m2 (Dralitem(r)) on days 1, 2 and 5 of
      a 5-day treatment. On days 3 and 4, subjects received the same dose of the test
      product (Dralitem(r)), or the reference product (Temodal(r)) on alternate days.
      The single dose of 200 mg/m2 was reached with three different temozolomide
      capsule strengths: 20, 100 and 250 mg. On days 3 and 4, blood samples were
      obtained for pharmacokinetic (PK) evaluation after drug administration. RESULTS:
      Bioequivalence assessment was made for the 90% confidence interval (CI) for the
      ratio of log-transformed means (MUT/MUR) of the area under the concentration-time
      curve (AUC from time zero to the final quantifiable sample [AUCt] and AUC from
      time zero to infinity [AUCinfinity]) and maximum concentration (C max) of both
      the test (Dralitem(r)) and reference (Temodal(r)) products. The point estimate
      and 90% CI of the ratios of C max, AUCt and AUCinfinity values were 94.37 (82.69
      107.69), 100.99 (97.81-104.28) and 101.53 (98.60-104.54), respectively. The ratio
      met the predefined bioequivalence criteria (i.e. 90% CI between 80.00 and 125.00)
      for C max and AUC. The most commonly reported adverse events (AE) on this study
      were vomiting, abdominal pain, asthenia and weakness. One subject experienced
      expressive aphasia, possibly unrelated to the study drug and with no significant
      sequelae upon recovery. No serious AEs or unexpected AEs were reported.
      CONCLUSIONS: Temozolomide Dralitem(r) capsules, 20, 100 and 250 mg, were
      bioequivalent to Temodal(r) capsules under fasting conditions in patients with
      CNS primary tumors, supporting that they are therapeutic equivalents.
      ClinicalTrials.gov Identifier: NCT02343081.

PMID- 28756608
TI  - Inhibition of chondroitin sulfate glycosaminoglycans incorporation affected
      odontoblast differentiation in cultured embryonic mouse molars.
AB  - Chondroitin sulfate proteoglycan (CSPG) is an important component of
      extracellular matrix (ECM), it is composed of a core protein and one or more
      chondroitin sulfate glycosaminoglycan side chains (CS-GAGs). To investigate the
      roles of its CS-GAGs in dentinogenesis, the mouse mandibular first molar tooth
      germs at early bell stage were cultivated with or without beta-xyloside. As
      expected, the CS-GAGs were inhibited on their incorporation to CSPGs by beta
      xyloside, accompanied by the change of morphology of the cultured tooth germs.
      The histological results and the transmission electron microscopy (TEM)
      investigation indicated that beta-xyloside exhibited obvious inhibiting effects
      on odontoblasts differentiation compared with the control group. Meanwhile the
      results of immunohistochemistry, in situ hybridization and quantitative RT-PCR
      for type I collagen, dentin matrix acidic phosphoprotein 1 and dentin
      sialophosphoprotein, the products of differentiated odontoblasts, further proved
      that odontoblasts differentiation was inhibited. Collagen fibers detected in TEM
      decreased and arranged in disorder as well. Thus we conclude that the inhibition
      of CS-GAGs incorporation to CSPGs can affect odontoblast differentiation in
      cultured embryonic mouse molars.

PMID- 28756609
TI  - Alternative renal biopsies: past and present.
AB  - Renal biopsy techniques have been used commonly worldwide for more than 70 years.
      They play an important role in the diagnosis, treatment, and prognosis of various
      renal diseases. Percutaneous renal biopsy (PRB) is currently the most important
      and widely used renal biopsy method. Although >90% of renal biopsies are PRBs, in
      certain settings, alternative renal biopsy techniques must be used, such as open,
      laparoscopic, transjugular, and transurethral renal biopsies. This review
      describes the history, advantages, and disadvantages of the various renal biopsy
      methods and discusses their current and future uses.

PMID- 28756610
TI  - Treatment of obesity-associated overactive bladder by the phosphodiesterase type
      4 inhibitor roflumilast.
AB  - PURPOSE: To prove that phosphodiesterase type-4 inhibitors could potentially
      treat obesity-associated overactive bladder through modulation of the systemic
      inflammatory response. METHODS: In this 12-week study, 90 female Sprague-Dawley
      rats were divided into three groups: (1) vehicle-treated normal diet (ND)-fed
      rats; (2) vehicle-treated high-fat diet (HFD)-fed rats; and (3) roflumilast
      treated HFD-fed rats. Oral roflumilast (5 mg/kg/day) was administered during the
      last 4 weeks of HFD feeding in the test group. At 12 weeks, a urodynamic study
      was performed in ten rats of each group. Bladder tissue was extracted, the
      bladder mucosa was separated under microscopy, and bladder detrusor smooth muscle
      (DSM) expression of TNF-alpha, interleukin (IL)-6, IL-1beta, and nuclear factor
      kappa B (NF-kappaB) were analyzed using Western blotting and quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR). RESULTS: Bodyweights of the
      HFD-fed rats significantly increased and were not ameliorated by roflumilast
      treatment. Cystometry evidenced augmented frequency and non-void contractions in
      obese rats that were also prevented by roflumilast. These alterations were
      accompanied by a markedly increased expression of TNF-alpha, IL-6, IL-1beta, and
      NF-kappaB in DSM of obese rats. Furthermore, roflumilast decreased expression of
      inflammatory factors in DSM. CONCLUSIONS: Oral treatment with roflumilast in rats
      fed an HFD restores normal bladder function and downregulates expression of
      inflammatory factors in the bladder.

PMID- 28756611
TI  - Expression of beta-adrenergic receptor subtypes in human normal and dilated
      ureter.
AB  - BACKGROUND: Ureter peristalsis is a basic physiological function regulated by
      myogenic and neurogenic factors. The distribution and function of beta-adrenergic
      receptors (beta-AR) in the human ureter remain unknown. The aim of this study was
      to investigate the expression of beta-AR subtypes in the normal and dilated human
      ureter. METHODS: The upper, middle, and lower segments of normal and dilated
      ureters were collected from patients undergoing surgery for carcinoma of the
      kidney and upper urinary tract and ureteral stenosis. The mucosa and muscular
      layers were separated. Expression of beta1-AR, beta2-AR, and beta3-AR mRNA and
      protein levels were detected by real-time PCR, western blot, and
      immunohistochemistry. RESULTS: In both mucosa and muscular layers, the mRNA and
      protein expressions of beta1-AR, beta2-AR, and beta3-AR were lower in the dilated
      ureter compared with the normal ureter. beta1-AR mRNA was significantly decreased
      (by 76.64%; P < 0.01) in the mucosa layer of the middle segment of the dilated
      ureter. beta1-AR and beta3-AR mRNA were significantly decreased (by 75.53 and
      53.62%, respectively; P < 0.01) in the muscular layer of the lower segment of the
      dilated ureter. Similar findings were observed for protein expression.
      CONCLUSIONS: The downregulation of beta-ARs after ureter dilation, particularly
      for beta1-AR and beta3-AR in the muscular layer, suggests a potential
      compensatory mechanism involving increased contraction of the ureter to push
      urine through the obstruction. Thus, beta-ARs may be a potential target for
      treatment of ureter obstruction.

PMID- 28756612
TI  - Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs.
AB  - This review describes the pharmacokinetic properties of the systemically
      administered antileishmanial drugs pentavalent antimony, paromomycin,
      pentamidine, miltefosine and amphotericin B (AMB), including their absorption,
      distribution, metabolism and excretion and potential drug-drug interactions. This
      overview provides an understanding of their clinical pharmacokinetics, which
      could assist in rationalising and optimising treatment regimens, especially in
      combining multiple antileishmanial drugs in an attempt to increase efficacy and
      shorten treatment duration. Pentavalent antimony pharmacokinetics are
      characterised by rapid renal excretion of unchanged drug and a long terminal half
      life, potentially due to intracellular conversion to trivalent antimony.
      Pentamidine is the only antileishmanial drug metabolised by cytochrome P450
      enzymes. Paromomycin is excreted by the kidneys unchanged and is eliminated
      fastest of all antileishmanial drugs. Miltefosine pharmacokinetics are
      characterized by a long terminal half-life and extensive accumulation during
      treatment. AMB pharmacokinetics differ per drug formulation, with a fast renal
      and faecal excretion of AMB deoxylate but a much slower clearance of liposomal
      AMB resulting in an approximately ten-fold higher exposure. AMB and pentamidine
      pharmacokinetics have never been evaluated in leishmaniasis patients. Studies
      linking exposure to effect would be required to define target exposure levels in
      dose optimisation but have only been performed for miltefosine. Limited research
      has been conducted on exposure at the drug's site of action, such as skin
      exposure in cutaneous leishmaniasis patients after systemic administration.
      Pharmacokinetic data on special patient populations such as HIV co-infected
      patients are mostly lacking. More research in these areas will help improve
      clinical outcomes by informed dosing and combination of drugs.

PMID- 28756614
TI  - Relatively Loose Flexion Gap Improves Patient-Reported Clinical Scores in
      Cruciate-Retaining Total Knee Arthroplasty.
AB  - Although appropriate soft tissue balancing is well recognized as essential
      procedure in total knee arthroplasty (TKA), poor relationship between
      intraoperative soft tissue balance and physician-reported clinical outcomes was
      reported. Since physician-derived scores are reported to be poorly related to
      patient-reported scores, patient-derived outcome scales have received a great
      deal of attention and have become increasingly important. Thus, it should be
      clarified whether intraoperative soft tissue balance influences patient-reported
      clinical outcomes. Therefore, the purpose of this study was to investigate the
      relationship between intraoperative soft tissue balance and patient-reported
      clinical outcomes in TKA. A total of 35 TKAs were performed in patients with
      varus-type osteoarthritis, using the tibia first technique with a navigation
      system. Soft tissue balance (joint component gap and varus/valgus ligament
      balance) with femoral component placement and temporarily repaired patellofemoral
      joint were intraoperatively assessed with an offset-type tensor under 40 lb of
      joint distraction force. Measurements were performed at 0, 10, 30, 60, 90, and
      120 degrees of knee flexion. Subjective clinical outcomes were assessed using the
      2011 Knee Society score, which consists of objective knee indicators, patient
      satisfaction, patient expectations, and functional activities at the minimum 1
      year follow-up. The relationship between each parameter in soft tissue balance
      and subjection clinical score was assessed using a simple linear regression
      model. Objective knee indicators, especially patient-reported symptoms, showed
      positive correlations with joint component gap difference of 90 to 0 and 120 to 0
      degrees. Patient satisfaction and expectations also exhibited positive
      correlations with joint component gap difference of 90 to 0 and 120 to 0 degrees.
      There were no correlations among any parameters of soft tissue balance and
      functional activities. The other parameters, including varus/valgus ligament
      balance, showed no statistical correlations with clinical scores. In conclusion,
      intraoperative soft tissue balance influenced the postoperative clinical
      outcomes, where a relatively loose flexion gap resulted in higher scores for the
      parameters of pain, patient satisfaction, and patient expectations.

PMID- 28756615
TI  - The Pellegrini-Stieda Lesion Dissected Historically.
AB  - The Pellegrini-Stieda lesion is a common finding on conventional X-rays. Whether
      it originates in the medial collateral ligament (MCL) of the knee or the medial
      head of the gastrocnemius muscle or another structure remains under debate. We
      discuss the difference in the articles by Pellegrini and Stieda and follow the
      vision on the origin of the lesion through time. A systematic research in
      PubMed/MEDLINE was conducted, identifying all articles on the Pellegrini-Stieda
      lesion and analyzing them for proposed origin of the lesion. The articles with
      their conclusion based on either finding during surgery or magnetic resonance
      imaging (MRI)/computed tomography were analyzed in more detail. Our
      PubMed/Medline search identified 4,997 articles. After exclusion of articles that
      were not on the Pellegrini-Stieda lesion and of doubles, 27 articles remained. By
      checking the references manually, 10 more articles were identified. Proposed
      origins were MCL, medial gastrocnemius, adductor magnus, vastus medialis, deep
      MCL, and superficial MCL. Although the MCL was most often coined as origin of the
      lesion (54% overall, 25% on MRI, and 57% during surgery), many cases remained
      undecided (50% on MRI) or no specific structure was found to be the origin (29%
      during surgery). There are diverse proposed origins of a calcification on the
      medial side of the knee. The eponymous term Pellegrini-Stieda lesion seems
      fitting, as it comprises two different thoughts on the origin of the lesion. MRI
      seems to be a noninvasive and quite accurate method for future research.

PMID- 28756613
TI  - Phase II study of paclitaxel associated with lipid core nanoparticles (LDE) as
      third-line treatment of patients with epithelial ovarian carcinoma.
AB  - Ovarian cancer is often diagnosed at advanced stages, when poorly responsive to
      standard treatment. First-line treatment consists in schemes including
      cytoreductive surgery followed by adjuvant chemotherapy schemes with platinum and
      taxane derivatives. Second-line regimens are based on gemcitabine and liposomal
      doxorubicin. Third line is often not worthwhile because of the high toxicity with
      poor response to treatment. Previously, we showed that paclitaxel (PTX) carried
      in non-protein lipid core nanoparticles (LDE) resembling the chemical structure
      of LDL has remarkably reduced toxicity. Here, the hypothesis was tested whether
      PTX-LDE could safely benefit patients in third-line treatment setting. Fourteen
      women unresponsive to second-line chemotherapy for ovarian cancer, aged 61 +/- 10
      years, clinical stage IV and TqNqM1, were included. PTX-LDE was administered at
      175 mg/m2, 3/3 week dose. Patients were submitted to clinical examinations before
      each chemotherapy cycle. Serum biochemistry and imaging examinations to monitor
      disease progression were performed. In total, 74 cycles of chemotherapy were done
      and, in all cycles, clinical or laboratorial toxicities were not observed. Median
      progression-free survival (PFS) was 3.0 months (95% CI 2.0-3.9). In four
      patients, PFS was >6 months and in 2 > 1 year. The unpreceded, striking absence
      of toxicity and consistently long PFS, compared to previous results, indicate
      that at least 4 among 14 patients had tumor arrest by the treatment and clear
      benefit of PTX-LDE at third-line setting. The absence of observable toxicity
      allows dose escalating to improve response to treatment, as perspective to be
      tested in the ensuing studies.

PMID- 28756617
TI  - Antioxidant vitamin and mineral supplements for preventing age-related macular
      degeneration.
AB  - BACKGROUND: There is inconclusive evidence from observational studies to suggest
      that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C,
      and E) or minerals (selenium and zinc) may be less likely to develop age-related
      macular degeneration (AMD). OBJECTIVES: To determine whether or not taking
      antioxidant vitamin or mineral supplements, or both, prevent the development of
      AMD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register)
      (2017, Issue 2), MEDLINE Ovid (1946 to 29 March 2017), Embase Ovid (1947 to 29
      March 2017), AMED (Allied and Complementary Medicine Database) (1985 to 29 March
      2017), OpenGrey (System for Information on Grey Literature in Europe)
      (www.opengrey.eu/); searched 29 March 2017, the ISRCTN registry
      (www.isrctn.com/editAdvancedSearch); searched 29 March 2017, ClinicalTrials.gov
      (www.clinicaltrials.gov); searched 29 March 2017 and the WHO International
      Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched
      29 March 2017. We did not use any date or language restrictions in the electronic
      searches for trials. SELECTION CRITERIA: We included all randomised controlled
      trials (RCTs) comparing an antioxidant vitamin or mineral supplement (alone or in
      combination) to control. DATA COLLECTION AND ANALYSIS: Both review authors
      independently assessed risk of bias in the included studies and extracted data.
      One author entered data into RevMan 5; the other author checked the data entry.
      We pooled data using a fixed-effect model. We graded the certainty of the
      evidence using GRADE. MAIN RESULTS: We included a total of five RCTs in this
      review with data available for 76,756 people. The trials were conducted in
      Australia, Finland, and the USA, and investigated vitamin C, vitamin E, beta
      carotene, and multivitamin supplements. All trials were judged to be at low risk
      of bias.Four studies reported the comparison of vitamin E with placebo. Average
      treatment and follow-up duration ranged from 4 to 10 years. Data were available
      for a total of 55,614 participants. There was evidence that vitamin E supplements
      do not prevent the development of any AMD (risk ratio (RR) 0.97, 95% confidence
      interval (CI) 0.90 to 1.06; high-certainty evidence), and may slightly increase
      the risk of late AMD (RR 1.22, 95% CI 0.89 to 1.67; moderate-certainty evidence)
      compared with placebo. Only one study (941 participants) reported data separately
      for neovascular AMD and geographic atrophy. There were 10 cases of neovascular
      AMD (RR 3.62, 95% CI 0.77 to 16.95; very low-certainty evidence), and four cases
      of geographic atrophy (RR 2.71, 95% CI 0.28 to 26.0; very low-certainty
      evidence). Two trials reported similar numbers of adverse events in the vitamin E
      and placebo groups. Another trial reported excess of haemorrhagic strokes in the
      vitamin E group (39 versus 23 events, hazard ratio 1.74, 95% CI 1.04 to 2.91, low
      certainty evidence).Two studies reported the comparison of beta-carotene with
      placebo. These studies took place in Finland and the USA. Both trials enrolled
      men only. Average treatment and follow-up duration was 6 years and 12 years. Data
      were available for a total of 22,083 participants. There was evidence that beta
      carotene supplements did not prevent any AMD (RR 1.00, 95% CI 0.88 to 1.14; high
      certainty evidence) nor have an important effect on late AMD (RR 0.90, 95% CI
      0.65 to 1.24; moderate-certainty evidence). Only one study (941 participants)
      reported data separately for neovascular AMD and geographic atrophy. There were
      10 cases of neovascular AMD (RR 0.61, 95% CI 0.17 to 2.15; very low-certainty
      evidence) and 4 cases of geographic atrophy (RR 0.31 95% CI 0.03 to 2.93; very
      low-certainty evidence). Beta-carotene was associated with increased risk of lung
      cancer in people who smoked.One study reported the comparison of vitamin C with
      placebo, and multivitamin (Centrum Silver) versus placebo. This was a study in
      men in the USA with average treatment duration and follow-up of 8 years for
      vitamin C and 11 years for multivitamin. Data were available for a total of
      14,236 participants. AMD was assessed by self-report followed by medical record
      review. There was evidence that vitamin C supplementation did not prevent any AMD
      (RR 0.96, 95% CI 0.79 to 1.18; high-certainty evidence) or late AMD (RR 0.94,
      0.61 to 1.46; moderate-certainty evidence). There was a slight increased risk of
      any AMD (RR 1.21, 95% CI 1.02 to 1.43; moderate-certainty evidence) and late AMD
      (RR 1.22, 95% CI 0.88 to 1.69; moderate-certainty evidence) in the multivitamin
      group. Neovascular AMD and geographic atrophy were not reported separately.
      Adverse effects were not reported but there was possible increased risk of skin
      rashes in the multivitamin group.Adverse effects were not consistently reported
      in these eye studies, but there is evidence from other large studies that beta
      carotene increases the risk of lung cancer in people who smoke or who have been
      exposed to asbestos.None of the studies reported quality of life or resource use
      and costs. AUTHORS' CONCLUSIONS: Taking vitamin E or beta-carotene supplements
      will not prevent or delay the onset of AMD. The same probably applies to vitamin
      C and the multivitamin (Centrum Silver) investigated in the one trial reported to
      date. There is no evidence with respect to other antioxidant supplements, such as
      lutein and zeaxanthin. Although generally regarded as safe, vitamin supplements
      may have harmful effects, and clear evidence of benefit is needed before they can
      be recommended. People with AMD should see the related Cochrane Review on
      antioxidant vitamin and mineral supplements for slowing the progression of AMD,
      written by the same review team.

PMID- 28756616
TI  - PARP-1/PAR Activity in Cultured Human Lens Epithelial Cells Exposed to Two Levels
      of UVB Light.
AB  - This study investigated poly(ADP-ribose) polymerase-1 (PARP-1) activation in
      cultured human lens epithelial cells exposed to two levels of UVB light (312 nm
      peak wavelength), 0.014 and 0.14 J cm-2 ("low" and "high" dose, respectively). At
      the low dose, PARP-1 and poly(ADP-ribose) (PAR) polymers acted to repair DNA
      strand breaks rapidly with no subsequent major effects on either cell morphology
      or viability. However, following the high UVB dose, there was a dramatic second
      phase of PARP-1 activation, 90 min later, which included a sudden reappearance of
      DNA strand breaks, bursts of reactive oxygen species (ROS) formation within both
      the mitochondria and nucleus, a translocation of PAR from the nucleus to the
      mitochondria and an ultimate 70% loss of cell viability occurring after 24 h. The
      results provide evidence for an important role for PARP-1 in protecting the human
      lens epithelium against low levels of UVB light, and possibly participating in
      the triggering of cell death following exposure to toxic levels of radiation.

PMID- 28756618
TI  - Antioxidant vitamin and mineral supplements for slowing the progression of age
      related macular degeneration.
AB  - BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in
      the retina by reacting with free radicals that are produced in the process of
      light absorption. Higher dietary levels of antioxidant vitamins and minerals may
      reduce the risk of progression of age-related macular degeneration (AMD).
      OBJECTIVES: The objective of this review was to assess the effects of antioxidant
      vitamin or mineral supplementation on the progression of AMD in people with AMD.
      SEARCH METHODS: We searched CENTRAL (2017, Issue 2), MEDLINE Ovid (1946 to March
      2017), Embase Ovid (1947 to March 2017), AMED (1985 to March 2017), OpenGrey
      (System for Information on Grey Literature in Europe, the ISRCTN registry
      (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov)
      and the WHO International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). We did not use any date or language restrictions
      in the electronic searches for trials. We last searched the electronic databases
      on 29 March 2017. SELECTION CRITERIA: We included randomised controlled trials
      (RCTs) that compared antioxidant vitamin or mineral supplementation (alone or in
      combination) to placebo or no intervention, in people with AMD. DATA COLLECTION
      AND ANALYSIS: Both review authors independently assessed risk of bias in the
      included studies and extracted data. One author entered data into RevMan 5; the
      other author checked the data entry. We graded the certainty of the evidence
      using GRADE. MAIN RESULTS: We included 19 studies conducted in USA, Europe,
      China, and Australia. We judged the trials that contributed data to the review to
      be at low or unclear risk of bias.Nine studies compared multivitamins with
      placebo (7 studies) or no treatment (2 studies) in people with early and moderate
      AMD. The duration of supplementation and follow-up ranged from nine months to six
      years; one trial followed up beyond two years. Most evidence came from the Age
      Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins
      were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence
      interval (CI) 0.58 to 0.90; 2445 participants; 3 RCTs; moderate-certainty
      evidence). In people with very early signs of AMD, who are at low risk of
      progression, this would mean that there would be approximately 4 fewer cases of
      progression to late AMD for every 1000 people taking vitamins (1 fewer to 6 fewer
      cases). In people at high risk of progression (i.e. people with moderate AMD)
      this would correspond to approximately 8 fewer cases of progression for every 100
      people taking vitamins (3 fewer to 13 fewer). In one study of 1206 people, there
      was a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to
      0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51
      to 1.10; moderate-certainty evidence) and a lower risk of losing 3 or more lines
      of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; 1791 participants; moderate
      certainty evidence). Low-certainty evidence from one study of 110 people
      suggested higher quality of life scores (National Eye Institute Visual Function
      Questionnaire) in treated compared with the non-treated people after 24 months
      (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). Six studies compared lutein
      (with or without zeaxanthin) with placebo. The duration of supplementation and
      follow-up ranged from six months to five years. Most evidence came from the
      AREDS2 study in the USA. People taking lutein or zeaxanthin may have similar or
      slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01;
      6891 eyes; low-certainty evidence), neovascular AMD (RR 0.92, 95% CI 0.84 to
      1.02; 6891 eyes; low-certainty evidence), and geographic atrophy (RR 0.92, 95% CI
      0.80 to 1.05; 6891 eyes; low-certainty evidence). A similar risk of progression
      to visual loss of 15 or more letters was seen in the lutein and control groups
      (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of
      life (measured with Visual Function Questionnaire) was similar between groups in
      one study of 108 participants (MD 1.48, 95% -5.53 to 8.49, moderate-certainty
      evidence). One study, conducted in Australia, compared vitamin E with placebo.
      This study randomised 1204 people to vitamin E or placebo, and followed up for
      four years. Participants were enrolled from the general population; 19% had AMD.
      The number of late AMD events was low (N = 7) and the estimate of effect was
      uncertain (RR 1.36, 95% CI 0.31 to 6.05, very low-certainty evidence). There were
      no data on neovascular AMD or geographic atrophy.There was no evidence of any
      effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47, low-certainty
      evidence). There were no data on quality of life. Five studies compared zinc with
      placebo. The duration of supplementation and follow-up ranged from six months to
      seven years. People taking zinc supplements may be less likely to progress to
      late AMD (OR 0.83, 95% CI 0.70 to 0.98; 3790 participants; 3 RCTs; low-certainty
      evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; 2442 participants; 1
      RCT; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to
      1.10; 2442 participants; 1 RCT; moderate-certainty evidence), or visual loss (OR
      0.87, 95% CI 0.75 to 1.00; 3791 participants; 2 RCTs; moderate-certainty
      evidence). There were no data reported on quality of life.Very low-certainty
      evidence was available on adverse effects because the included studies were
      underpowered and adverse effects inconsistently reported. AUTHORS' CONCLUSIONS:
      People with AMD may experience some delay in progression of the disease with
      multivitamin antioxidant vitamin and mineral supplementation. This finding was
      largely drawn from one large trial, conducted in a relatively well-nourished
      American population. We do not know the generalisability of these findings to
      other populations. Although generally regarded as safe, vitamin supplements may
      have harmful effects. A systematic review of the evidence on harms of vitamin
      supplements is needed. Supplements containing lutein and zeaxanthin are heavily
      marketed for people with age-related macular degeneration but our review shows
      they may have little or no effect on the progression of AMD.

PMID- 28756619
TI  - Prostate carcinoma with amphicrine features: further refining the spectrum of
      neuroendocrine differentiation in tumours of primary prostatic origin?
AB  - AIMS: The current World Health Organization classification categorises high-grade
      neuroendocrine (NE) carcinomas of the prostate into small-cell and large-cell
      types. A distinct form of carcinoma showing synchronous dual exocrine and NE
      differentiation, termed amphicrine carcinoma, has been described at various other
      sites, primarily within the gastrointestinal tract. The aim of this study was to
      investigate the clinicopathological features of a series of metastatic prostate
      carcinoma (PCa) cases with amphicrine features. METHODS AND RESULTS: Five cases
      of high-grade PCa showing an amphicrine immunohistochemical phenotype were
      prospectively collected. The serum prostate-specific antigen (PSA) level at
      diagnosis ranged from 38 ng/ml to 992 ng/ml (median 200 ng/ml). All five patients
      had metastatic disease, four at initial presentation. Microscopically, the
      tumours showed a solid/nested growth pattern composed of cells with amphophilic
      cytoplasm, vesicular nuclei, and macronucleoli. Morphological features of small
      cell or large-cell NE carcinoma were absent. As compared with conventional high
      grade PCa, the tumour cells showed a higher level of nuclear pleomorphism, brisk
      mitotic activity, and a high Ki67 proliferation index (median 50%). All cases
      showed immunohistochemical positivity for PSA, androgen receptor, and prostate
      specific acid phosphatase, combined with diffuse or confluent/non-focal
      positivity for chromogranin-A and synaptophysin. Two hormone-naive cases showed a
      clinical response to androgen deprivation therapy. CONCLUSION: This series
      highlights a previously undefined, clinically aggressive variant of PCa showing
      dual exocrine and NE differentiation, for which we are proposing the term PCa
      with amphicrine features. Increased recognition of these tumours may lead to a
      better understanding of their biology, and ultimately improve their clinical
      management.

PMID- 28756620
TI  - MDM4 amplification in a case of de-differentiated liposarcoma and in-silico data
      supporting an oncogenic event alternative to MDM2 amplification in a subset of
      cases.

PMID- 28756621
TI  - Microscopic tubal sex-cord proliferations with a Sertoli cell tumour pattern and
      ovarian-type stromal transformation of the fimbriae.

PMID- 28756622
TI  - Fully automatic, multiorgan segmentation in normal whole body magnetic resonance
      imaging (MRI), using classification forests (CFs), convolutional neural networks
      (CNNs), and a multi-atlas (MA) approach.
AB  - PURPOSE: As part of a program to implement automatic lesion detection methods for
      whole body magnetic resonance imaging (MRI) in oncology, we have developed,
      evaluated, and compared three algorithms for fully automatic, multiorgan
      segmentation in healthy volunteers. METHODS: The first algorithm is based on
      classification forests (CFs), the second is based on 3D convolutional neural
      networks (CNNs) and the third algorithm is based on a multi-atlas (MA) approach.
      We examined data from 51 healthy volunteers, scanned prospectively with a
      standardized, multiparametric whole body MRI protocol at 1.5 T. The study was
      approved by the local ethics committee and written consent was obtained from the
      participants. MRI data were used as input data to the algorithms, while training
      was based on manual annotation of the anatomies of interest by clinical MRI
      experts. Fivefold cross-validation experiments were run on 34 artifact-free
      subjects. We report three overlap and three surface distance metrics to evaluate
      the agreement between the automatic and manual segmentations, namely the dice
      similarity coefficient (DSC), recall (RE), precision (PR), average surface
      distance (ASD), root-mean-square surface distance (RMSSD), and Hausdorff distance
      (HD). Analysis of variances was used to compare pooled label metrics between the
      three algorithms and the DSC on a 'per-organ' basis. A Mann-Whitney U test was
      used to compare the pooled metrics between CFs and CNNs and the DSC on a 'per
      organ' basis, when using different imaging combinations as input for training.
      RESULTS: All three algorithms resulted in robust segmenters that were effectively
      trained using a relatively small number of datasets, an important consideration
      in the clinical setting. Mean overlap metrics for all the segmented structures
      were: CFs: DSC = 0.70 +/- 0.18, RE = 0.73 +/- 0.18, PR = 0.71 +/- 0.14, CNNs: DSC
      = 0.81 +/- 0.13, RE = 0.83 +/- 0.14, PR = 0.82 +/- 0.10, MA: DSC = 0.71 +/- 0.22,
      RE = 0.70 +/- 0.34, PR = 0.77 +/- 0.15. Mean surface distance metrics for all the
      segmented structures were: CFs: ASD = 13.5 +/- 11.3 mm, RMSSD = 34.6 +/- 37.6 mm
      and HD = 185.7 +/- 194.0 mm, CNNs; ASD = 5.48 +/- 4.84 mm, RMSSD = 17.0 +/- 13.3
      mm and HD = 199.0 +/- 101.2 mm, MA: ASD = 4.22 +/- 2.42 mm, RMSSD = 6.13 +/- 2.55
      mm, and HD = 38.9 +/- 28.9 mm. The pooled performance of CFs improved when all
      imaging combinations (T2w + T1w + DWI) were used as input, while the performance
      of CNNs deteriorated, but in neither case, significantly. CNNs with T2w images as
      input, performed significantly better than CFs with all imaging combinations as
      input for all anatomical labels, except for the bladder. CONCLUSIONS: Three state
      of-the-art algorithms were developed and used to automatically segment major
      organs and bones in whole body MRI; good agreement to manual segmentations
      performed by clinical MRI experts was observed. CNNs perform favorably, when
      using T2w volumes as input. Using multimodal MRI data as input to CNNs did not
      improve the segmentation performance.

PMID- 28756623
TI  - Spatial and temporal drivers of avian population dynamics across the annual
      cycle.
AB  - Untangling the spatial and temporal processes that influence population dynamics
      of migratory species is challenging, because changes in abundance are shaped by
      variation in vital rates across heterogeneous habitats and throughout the annual
      cycle. We developed a full-annual-cycle, integrated, population model and used
      demographic data collected between 2011 and 2014 in southern Indiana and Belize
      to estimate stage-specific vital rates of a declining migratory songbird, the
      Wood Thrush (Hylocichla mustelina). Our primary objective was to understand how
      spatial and temporal variation in demography contributes to local and regional
      population growth. Our full-annual-cycle model allowed us to estimate (1) age
      specific, seasonal survival probabilities, including latent survival during both
      spring and autumn migration, and (2) how the relative contribution of vital rates
      to population growth differed among habitats. Wood Thrushes in our study
      populations experienced the lowest apparent survival rates during migration and
      apparent survival was lower during spring migration than during fall migration.
      Both mortality and high dispersal likely contributed to low apparent survival
      during spring migration. Population growth in high-quality habitat was most
      sensitive to variation in fecundity and apparent survival of juveniles during
      spring migration, whereas population growth in low-quality sites was most
      sensitive to adult apparent breeding-season survival. These results elucidate how
      full-annual-cycle vital rates, particularly apparent survival during migration,
      interact with spatial variation in habitat quality to influence population
      dynamics in migratory species.

PMID- 28756624
TI  - Double-edged sword of mesenchymal stem cells: Cancer-promoting versus therapeutic
      potential.
AB  - Mesenchymal stem cells (MSCs) derived from adipose tissue, bone marrow, cord
      blood, and other tissues, have recently attracted much attention as potential
      therapeutic agents in various diseases because of their trans-differentiation
      capacity. However, recent studies have suggested that MSCs also appear to
      contribute to tumor pathogenesis by supporting tumor microenvironments,
      increasing tumor growth, and eliciting antitumor immune responses. Although some
      studies suggest that MSCs have inhibitory effects on tumor development, they are
      overwhelmed by a number of studies showing that MSCs exert stimulatory effects on
      tumor pathogenesis. In the present review, we summarize a number of findings to
      provide current information about the therapeutic potential of MSCs in various
      diseases. We then discuss the potential roles of MSCs in tumor progression.

PMID- 28756625
TI  - Sofosbuvir/velpatasvir in patients with hepatitis C virus genotypes 1-6 and
      compensated cirrhosis or advanced fibrosis.
AB  - BACKGROUND & AIMS: Patients with chronic hepatitis C virus infection and advanced
      fibrosis (Metavir F3) or cirrhosis (Metavir F4) have been identified as a
      priority group for immediate treatment. We evaluated the safety and efficacy of
      sofosbuvir-velpatasvir in patients with hepatitis C virus genotype 1-6 infection
      and compensated cirrhosis or advanced fibrosis. METHODS: This retrospective
      analysis included 501 patients with compensated cirrhosis or advanced fibrosis
      (F3/F4), as defined by >0.59 on Fibrotest, >9.5 kPa on Fibroscan, or F3/F4
      (Metavir) or F4 (Ishak) on liver biopsy. Patients received sofosbuvir-velpatasvir
      for 12 weeks. Sustained virological response 12 weeks after treatment was
      determined. RESULTS: Forty-four per cent of patients had cirrhosis. Sustained
      virological response 12 weeks after treatment was achieved by 98% of patients
      (490/501; 95% confidence interval, 96-99). Sustained virological response 12
      weeks after treatment rates were 100% for hepatitis C virus genotypes 2 (85/85),
      4 (60/60), 5 (13/13), and 6 (20/20). Sustained virological response 12 weeks
      after treatment rates were 98% (167/170) in hepatitis C virus genotype 1 patients
      and 95% (145/153) in hepatitis C virus genotype 3 patients. Among patients with
      cirrhosis 96% (212/220) achieved sustained virological response 12 weeks after
      treatment, vs 99% (278/281) for those with advanced fibrosis. Sustained
      virological response 12 weeks after treatment was 98% (306/311) for treatment
      naive patients and 97% (184/190) for treatment-experienced patients. No patients
      discontinued treatment due to adverse events. Eight patients reported nine
      serious adverse events; none was considered related to study procedures or drugs.
      CONCLUSIONS: Sofosbuvir plus velpatasvir is highly effective and safe for
      treating patients with hepatitis C virus genotypes 1, 2, 3, 4, 5 or 6 and
      advanced fibrosis or compensated cirrhosis.

PMID- 28756626
TI  - Myths and methodologies: Making sense of exercise mass and water balance.
AB  - NEW FINDINGS: What is the topic of this review? There is a need to revisit the
      basic principles of exercise mass and water balance, the use of common equations
      and the practice of interpreting outcomes. What advances does it highlight? We
      propose use of the following equation as a way of simplifying exercise mass and
      water balance calculations in conditions where food is not consumed and waste is
      not excreted: ?body mass - 0.20 g/kcal-1  = ?body water. The relative efficacy of
      exercise drinking behaviours can be judged using the following equation:
      percentage dehydration = [(?body mass - 0.20 g kcal-1 )/starting body mass] *
      100. Changes in body mass occur because of flux in liquids, solids and gases.
      This knowledge is crucial for understanding metabolism, health and human water
      needs. In exercise science, corrections to observed changes in body mass to
      estimate water balance are inconsistently applied and often misinterpreted,
      particularly after prolonged exercise. Although acute body mass losses in
      response to exercise can represent a close surrogate for body water losses, the
      discordance between mass and water balance equivalence becomes increasingly
      inaccurate as more and more energy is expended. The purpose of this paper is
      briefly to clarify the roles that respiratory water loss, gas exchange and
      metabolic water production play in the correction of body mass changes for fluid
      balance determinations during prolonged exercise. Computations do not include
      waters of association with glycogen because any movement of water among body
      water compartments contributes nothing to water or mass flux from the body.
      Estimates of sweat loss from changes in body mass should adjust for non-sweat
      losses when possible. We propose use of the following equation as a way of
      simplifying the study of exercise mass and water balance: ?body mass - 0.20 g
      kcal-1  = ?body water. This equation directly controls for the influence of
      energy expenditure on body mass balance and the approximate offsetting
      equivalence of respiratory water loss and metabolic water production on body
      water balance. The relative efficacy of exercise drinking behaviours can be
      judged using the following equation: percentage dehydration = [(?body mass - 0.20
      g kcal-1 )/starting body mass] * 100.

PMID- 28756628
TI  - Harnessing electronic healthcare data for wound care research: Wound registry
      analytic guidelines for less-biased analyses.
AB  - Publications based on large healthcare databases that contain data pertaining to
      wound-related outcomes are starting to appear more frequently. However, concern
      exists in regard to study design adequacy, the methodology used to minimize
      misclassifications, bias, and confounding, and lack of full reporting. The STROBE
      guidelines were published to encourage fuller reporting of observational studies
      and have now been extended using the RECORD statement to better document
      routinely collected healthcare data. In this paper, elements of the RECORD
      statement have been used to create guidelines for study design, cohort matching,
      reporting criteria, and analysis frameworks in regard to analyses of populations
      involving comparative effectiveness research. It is recommended that researchers
      present full data analysis with minimal inclusion and exclusion criteria and
      preplanned subgroups analyses rather than attempt to emulate randomized
      controlled trials, as patterns of product administration are likely to be vastly
      different to those using controlled trials; moreover, missing data are very
      common. Suggestions for creating better matched cohorts, classification of wound-
      and patient-related variables, and a rationale for reporting at a minimum a
      particular set of benchmarks to better characterize wound care populations is
      also presented. Adherence to these guidelines would improve the credibility of
      studies and make comparisons between studies much easier. Finally, an adaptation
      of the Cochrane risk of bias tool is presented in connection with the proposed
      guidelines for systematic reviewers to assess these kinds of retrospective
      studies.

PMID- 28756627
TI  - Pathogen-reduced platelets for the prevention of bleeding.
AB  - BACKGROUND: Platelet transfusions are used to prevent and treat bleeding in
      people who are thrombocytopenic. Despite improvements in donor screening and
      laboratory testing, a small risk of viral, bacterial, or protozoal contamination
      of platelets remains. There is also an ongoing risk from newly emerging blood
      transfusion-transmitted infections for which laboratory tests may not be
      available at the time of initial outbreak.One solution to reduce the risk of
      blood transfusion-transmitted infections from platelet transfusion is
      photochemical pathogen reduction, in which pathogens are either inactivated or
      significantly depleted in number, thereby reducing the chance of transmission.
      This process might offer additional benefits, including platelet shelf-life
      extension, and negate the requirement for gamma-irradiation of platelets.
      Although current pathogen-reduction technologies have been proven to reduce
      pathogen load in platelet concentrates, a number of published clinical studies
      have raised concerns about the effectiveness of pathogen-reduced platelets for
      post-transfusion platelet count recovery and the prevention of bleeding when
      compared with standard platelets.This is an update of a Cochrane review first
      published in 2013. OBJECTIVES: To assess the effectiveness of pathogen-reduced
      platelets for the prevention of bleeding in people of any age requiring platelet
      transfusions. SEARCH METHODS: We searched for randomised controlled trials (RCTs)
      in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane
      Library 2016, Issue 9), MEDLINE (from 1946), Embase (from 1974), CINAHL (from
      1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases
      to 24 October 2016. SELECTION CRITERIA: We included RCTs comparing the
      transfusion of pathogen-reduced platelets with standard platelets, or comparing
      different types of pathogen-reduced platelets. DATA COLLECTION AND ANALYSIS: We
      used the standard methodological procedures expected by Cochrane. MAIN RESULTS:
      We identified five new trials in this update of the review. A total of 15 trials
      were eligible for inclusion in this review, 12 completed trials (2075
      participants) and three ongoing trials. Ten of the 12 completed trials were
      included in the original review. We did not identify any RCTs comparing the
      transfusion of one type of pathogen-reduced platelets with another.Nine trials
      compared Intercept(r) pathogen-reduced platelets to standard platelets, two
      trials compared Mirasol(r) pathogen-reduced platelets to standard platelets; and
      one trial compared both pathogen-reduced platelets types to standard platelets.
      Three RCTs were randomised cross-over trials, and nine were parallel-group
      trials. Of the 2075 participants enrolled in the trials, 1981 participants
      received at least one platelet transfusion (1662 participants in Intercept(r)
      platelet trials and 319 in Mirasol(r) platelet trials).One trial included
      children requiring cardiac surgery (16 participants) or adults requiring a liver
      transplant (28 participants). All of the other participants were thrombocytopenic
      individuals who had a haematological or oncological diagnosis. Eight trials
      included only adults.Four of the included studies were at low risk of bias in
      every domain, while the remaining eight included studies had some threats to
      validity.Overall, the quality of the evidence was low to high across different
      outcomes according to GRADE methodology.We are very uncertain as to whether
      pathogen-reduced platelets increase the risk of any bleeding (World Health
      Organization (WHO) Grade 1 to 4) (5 trials, 1085 participants; fixed-effect risk
      ratio (RR) 1.09, 95% confidence interval (CI) 1.02 to 1.15; I2 = 59%, random
      effect RR 1.14, 95% CI 0.93 to 1.38; I2 = 59%; low-quality evidence).There was no
      evidence of a difference between pathogen-reduced platelets and standard
      platelets in the incidence of clinically significant bleeding complications (WHO
      Grade 2 or higher) (5 trials, 1392 participants; RR 1.10, 95% CI 0.97 to 1.25; I2
      = 0%; moderate-quality evidence), and there is probably no difference in the risk
      of developing severe bleeding (WHO Grade 3 or higher) (6 trials, 1495
      participants; RR 1.24, 95% CI 0.76 to 2.02; I2 = 32%; moderate-quality
      evidence).There is probably no difference between pathogen-reduced platelets and
      standard platelets in the incidence of all-cause mortality at 4 to 12 weeks (6
      trials, 1509 participants; RR 0.81, 95% CI 0.50 to 1.29; I2 = 26%; moderate
      quality evidence).There is probably no difference between pathogen-reduced
      platelets and standard platelets in the incidence of serious adverse events (7
      trials, 1340 participants; RR 1.09, 95% CI 0.88 to 1.35; I2 = 0%; moderate
      quality evidence). However, no bacterial transfusion-transmitted infections
      occurred in the six trials that reported this outcome.Participants who received
      pathogen-reduced platelet transfusions had an increased risk of developing
      platelet refractoriness (7 trials, 1525 participants; RR 2.94, 95% CI 2.08 to
      4.16; I2 = 0%; high-quality evidence), though the definition of platelet
      refractoriness differed between trials.Participants who received pathogen-reduced
      platelet transfusions required more platelet transfusions (6 trials, 1509
      participants; mean difference (MD) 1.23, 95% CI 0.86 to 1.61; I2 = 27%; high
      quality evidence), and there was probably a shorter time interval between
      transfusions (6 trials, 1489 participants; MD -0.42, 95% CI -0.53 to -0.32; I2 =
      29%; moderate-quality evidence). Participants who received pathogen-reduced
      platelet transfusions had a lower 24-hour corrected-count increment (7 trials,
      1681 participants; MD -3.02, 95% CI -3.57 to -2.48; I2 = 15%; high-quality
      evidence).None of the studies reported quality of life.We did not evaluate any
      economic outcomes.There was evidence of subgroup differences in multiple
      transfusion trials between the two pathogen-reduced platelet technologies
      assessed in this review (Intercept(r) and Mirasol(r)) for all-cause mortality and
      the interval between platelet transfusions (favouring Intercept(r)). AUTHORS'
      CONCLUSIONS: Findings from this review were based on 12 trials, and of the 1981
      participants who received a platelet transfusion only 44 did not have a
      haematological or oncological diagnosis.In people with haematological or
      oncological disorders who are thrombocytopenic due to their disease or its
      treatment, we found high-quality evidence that pathogen-reduced platelet
      transfusions increase the risk of platelet refractoriness and the platelet
      transfusion requirement. We found moderate-quality evidence that pathogen-reduced
      platelet transfusions do not affect all-cause mortality, the risk of clinically
      significant or severe bleeding, or the risk of a serious adverse event. There was
      insufficient evidence for people with other diagnoses.All three ongoing trials
      are in adults (planned recruitment 1375 participants) with a haematological or
      oncological diagnosis.

PMID- 28756629
TI  - Optimal metabolic regulation along resource stoichiometry gradients.
AB  - Most heterotrophic organisms feed on substrates that are poor in nutrients
      compared to their demand, leading to elemental imbalances that may constrain
      their growth and function. Flexible carbon (C)-use efficiency (CUE, C used for
      growth over C taken up) can represent a strategy to reduce elemental imbalances.
      Here, we argue that metabolic regulation has evolved to maximise the organism
      growth rate along gradients of nutrient availability and translated this
      assumption into an optimality model that links CUE to substrate and organism
      stoichiometry. The optimal CUE is predicted to decrease with increasing substrate
      C-to-nutrient ratio, and increase with nutrient amendment. These predictions are
      generally confirmed by empirical evidence from a new database of c. 2200 CUE
      estimates, lending support to the hypothesis that CUE is optimised across levels
      of organisation (microorganisms and animals), in aquatic and terrestrial systems,
      and when considering nitrogen or phosphorus as limiting nutrients.

PMID- 28756631
TI  - Access to influenza immunisation services by HIV-positive patients in the UK.

PMID- 28756633
TI  - A brief commentary on 'Response letter to "What should be taken into account
      during study on immunoregulatory effects of helminths: a critical analyzing on
      downregulation of immune responses in asthmatic patients by ES products of
      Marshallagia marshalli"'.

PMID- 28756632
TI  - Lymphangiogenesis: From passive disseminator to dynamic metastatic enabler.

PMID- 28756630
TI  - DNA methylation of Th2 lineage determination genes at birth is associated with
      allergic outcomes in childhood.
AB  - BACKGROUND: There is now increasing evidence that asthma and atopy originate in
      part in utero, with disease risk being associated with the altered epigenetic
      regulation of genes. OBJECTIVE AND METHODS: To determine the relationship between
      variations in DNA methylation at birth and the development of allergic disease,
      we examined the methylation status of CpG loci within the promoter regions of
      Th1/2 lineage commitment genes (GATA3, IL-4, IL-4R, STAT4 and TBET) in umbilical
      cord DNA at birth in a cohort of infants from the Southampton Women's Survey (n =
      696) who were later assessed for asthma, atopic eczema and atopy. RESULTS: We
      found that higher methylation of GATA3 CpGs -2211/-2209 at birth was associated
      with a reduced risk of asthma at ages 3 (median ratio [median methylation in
      asthma group/median methylation in non-asthma group] = 0.74, P = .006) and 6-7
      (median ratio 0.90, P = .048) years. Furthermore, we demonstrated that the GATA3
      CpG loci associated with later risk of asthma lie within a NF-kappaB binding site
      and that methylation here blocks transcription factor binding to the GATA3
      promoter in the human Jurkat T-cell line. Associations between umbilical cord
      methylation of CpG loci within IL-4R with atopic eczema at 12 months (median
      ratio 1.02, P = .028), and TBET with atopy (median ratio 0.98, P = .017) at 6-7
      years of age were also observed. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings
      provide further evidence of a developmental contribution to the risk of later
      allergic disorders and suggest that involvement of epigenetic mechanisms in
      childhood asthma is already demonstrable at birth.

PMID- 28756634
TI  - Necrotizing sarcoid granulomatosis: A distinctive form of pulmonary granulomatous
      disease.
AB  - OBJECTIVES: To define the characteristics of necrotizing sarcoid granulomatosis
      (NGS) a very rare pulmonary disease hardly recognised by pulmonologists and
      pathologists. DATA SOURCE: PubMed was searched for the term necrotising or
      necrotizing sarcoid granulomatosis. STUDY SELECTION: All cases reported in the
      English literature were included. RESULTS: NGS is presented at all ages (range 8
      68 years) with a median age of 42 years old. It shows female (62%) and Caucasian
      (80%) predominance. The most frequent symptoms are cough, fever, dyspnoea and
      chest pain. Extra-pulmonary involvement is found in one third of the cases, with
      ocular being the most common (12.5%). At imaging, multiple nodules (64.75%) or a
      solitary mass (20.49%) are found accompanied by mediastinal lymphadenopathy at
      one third of the cases. It can be clinically mistaken for malignancy as it is
      tumour-like, increases rapidly in size and it is hyperfixating in PET-SCAN.
      Histologically, NGS is defined by large areas of necrosis, well-formed granulomas
      and vascularitis. CONCLUSION: NGS is a disease often confounded clinically with
      malignancy or with sarcoidosis even histologically when all criteria are not
      strictly applied. This review provides NGS' characteristics and discusses its
      differential diagnosis form sarcoidosis, Wegener granulomatosis and tuberculosis.

PMID- 28756635
TI  - Can ADMA play a role in determining pulmonary hypertension related to chronic
      obstructive pulmonary disease?
AB  - BACKGROUND AND AIMS: Asymmetric dimethylarginine (ADMA) decreases the levels of
      nitric oxide by inhibiting nitric oxide synthases. In this study, the possible
      role of ADMA in determining pulmonary hypertension (PH) in chronic obstructive
      pulmonary disease (COPD) patients was investigated. METHODS: Stable COPD patients
      who were admitted to pulmonology outpatient clinic were involved in the study.
      Forty healthy volunteers, with similar ages and sexes, were accepted as the
      control group. COPD patients were divided into two groups: 40 patients without PH
      (COPD group) and 40 COPD-related PH patients (COPD-PH group). Pulmonary function
      test, echocardiography and arterial blood analyses of all patients were
      performed. RESULTS: The mean age of patients was 69.21 +/- 10.62, and 15 of these
      patients were females. There was no significant difference between the two COPD
      groups in terms of age and sex (P > .05). There was no difference in PaO2 , SaO2
      , FEV1 and FEV1 /FVC values between the two COPD groups (P > .05). Serum ADMA
      levels were similar in the control and the COPD group (0.42 +/- 0.13 vs 0.43 +/-
      0.15), but it was significantly higher in the COPD-PH group compared to the
      control and the COPD group (0.49 +/- 0.14). A negative correlation was determined
      between serum ADMA levels and SaO2 levels (r = -.247, P = .028). A significant
      positive correlation observed between ADMA and systolic pulmonary artery pressure
      values (r = .627, P < .001) CONCLUSIONS: In conclusion, high levels of serum ADMA
      levels may be able to determine the presence of PH.

PMID- 28756636
TI  - Medicaid expansion and chronic obstructive pulmonary disease among low-income
      adults in the United States.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is common but often
      underdiagnosed in the United States (US). Public health insurance coverage
      expansion may increase the prevalence of diagnosed COPD due to improved access to
      care and diagnosis. OBJECTIVE: We sought to determine the effects of Medicaid
      expansion on the prevalence of diagnosed COPD among low-income US adults.
      METHODS: The 2011-2015 Behavioral Risk Factor Surveillance System survey data
      were used to identify adults with annual household income <$50 000. The outcome
      was self-report of being diagnosed with COPD by a health-care provider.
      Difference-in-difference logistic regression contrasted the influence of period
      (pre-expansion, 2011-2013, vs post-expansion, 2014-2015) between states
      participating and opting out of Medicaid expansion. RESULTS: Data on 521 622
      respondents were analysed. The prevalence of diagnosed COPD was 7% in Medicaid
      expansion states and 8% in non-participating states. In participating states,
      lack of health insurance among low-income adults decreased from 32% to 21% after
      Medicaid expansion (P < .001), but the prevalence of diagnosed COPD was
      unchanged. Multivariable logistic regression confirmed that residents of
      participating states surveyed after Medicaid expansion were no more likely to
      report diagnosed COPD than residents of these states surveyed before Medicaid
      expansion (OR = 1.03; 95% CI: 0.97, 1.10; P = .276). CONCLUSIONS: Notwithstanding
      increased health insurance coverage among low-income adults after Medicaid
      expansion, this policy did not increase the prevalence of diagnosed COPD. Access
      to primary care among new Medicaid enrollees and practices of diagnosing COPD in
      this setting should be evaluated to reduce the extent of undiagnosed COPD in
      socioeconomically disadvantaged groups.

PMID- 28756637
TI  - Sputum bacteriology and clinical response to antibiotics in moderate exacerbation
      of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Presence of purulent sputum during an acute exacerbation of chronic
      obstructive pulmonary disease (AECOPD) is considered sufficient indication for
      starting empirical antibiotics. We investigated the relationship between
      detection of potentially pathogenic bacteria (PPB) using sputum culture or
      polymerase chain reaction (PCR) and clinical response and sought the risk factors
      for PPB growth. METHODS: In 342 outpatients with AECOPD, we compared detection
      rates of H. influenzae (HI) and S. pneumoniae (SP) using conventional sputum
      culture versus PCR. The utility of either technique to predict clinical cure or
      failure after effective antibiotics was assessed. The factors predicting positive
      sputum cultures were evaluated using logistic regression. RESULTS: Using sputum
      culture, 132 PPB were detected. The predominant bacteria were HI (40.9%) and SP
      (19.7%). Detection of HI or SP in sputum was higher using PCR than culture growth
      (60.8% vs 18.6%; P < .001). Clinical response was not affected by the results of
      either technique. Independent risk factors for PPB isolation were Gram-negative
      bacteria on sputum smear (OR 15.78, 95% CI 6.38-39.06; P < .001), sputum
      purulence (OR 2.31, 95% CI, 1.05-5.11; P = .04), body temperature (OR 0.16, 95%
      CI 0.05-0.54; P = .003), albumin level (OR 0.29, 95% CI 0.09-0.88; P = .03) and
      dyspnea grade (OR 0.51, 95% CI 0.27-0.96; P = .04). CONCLUSIONS: Neither culture
      growth nor PCR positivity for HI or SP in sputum predicted clinical response to
      antibiotics; therefore, these tests are not necessary for outpatients with
      AECOPD. Examining Gram-staining and purulence on sputum smear, however, was
      significant to predict PPB growth in sputum.

PMID- 28756638
TI  - Structure-based discovery of new selective small-molecule sirtuin 5 inhibitors.
AB  - Human sirtuin 5 (SIRT5) is a protein deacylase regulating metabolic pathways and
      stress responses and is implicated in metabolism-related diseases. Small-molecule
      inhibitors for SIRT5 are sought as chemical tools and potential therapeutics.
      Herein, we proposed a customized virtual screening approach targeting
      catalytically important and unique residues Tyr102 and Arg105 of SIRT5. Of the 20
      tested virtual screening hits, six compounds displayed marked inhibitory
      activities against SIRT5. For the hit compound 19, a series of newly synthesized
      (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues were
      carried out structure-activity relationship analyses, resulting in new more
      potent inhibitors, among which 37 displayed the most potent inhibition to SIRT5
      with an IC50 value of 5.59 +/- 0.75 MUM. The biochemical studies revealed that 37
      likely acts via competitive inhibition with the succinyl-lysine substrate, rather
      than the NAD+ cofactor, and it manifested substantial selectivity for SIRT5 over
      SIRT2 and SIRT6. This study will aid further efforts to develop new selective
      SIRT5 inhibitors as tools and therapeutics.

PMID- 28756640
TI  - Signalling requirements for Erwinia amylovora-induced disease resistance, callose
      deposition and cell growth in the non-host Arabidopsis thaliana.
AB  - Erwinia amylovora is the causal agent of the fire blight disease in some plants
      of the Rosaceae family. The non-host plant Arabidopsis serves as a powerful
      system for the dissection of mechanisms of resistance to E. amylovora. Although
      not yet known to mount gene-for-gene resistance to E. amylovora, we found that
      Arabidopsis activated strong defence signalling mediated by salicylic acid (SA),
      with kinetics and amplitude similar to that induced by the recognition of the
      bacterial effector avrRpm1 by the resistance protein RPM1. Genetic analysis
      further revealed that SA signalling, but not signalling mediated by ethylene (ET)
      and jasmonic acid (JA), is required for E. amylovora resistance. Erwinia
      amylovora induces massive callose deposition on infected leaves, which is
      independent of SA, ET and JA signalling and is necessary for E. amylovora
      resistance in Arabidopsis. We also observed tumour-like growths on E. amylovora
      infected Arabidopsis leaves, which contain enlarged mesophyll cells with
      increased DNA content and are probably a result of endoreplication. The formation
      of such growths is largely independent of SA signalling and some E. amylovora
      effectors. Together, our data reveal signalling requirements for E. amylovora
      induced disease resistance, callose deposition and cell fate change in the non
      host plant Arabidopsis. Knowledge from this study could facilitate a better
      understanding of the mechanisms of host defence against E. amylovora and
      eventually improve host resistance to the pathogen.

PMID- 28756641
TI  - Introduction to Myths & Methodologies series.
AB  - Podcast available at: http://www.yada
      yada.co.uk/wiley/ExperimentalPhysiology/audio/Mike_Mnm_Aug17.mp3.

PMID- 28756639
TI  - Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical
      practice guidelines by the Chinese Thoracic Society, Chinese Medical Association.
AB  - Community-acquired pneumonia (CAP) in adults is an infectious disease with high
      morbidity in China and the rest of the world. With the changing pattern in the
      etiological profile of CAP and advances in medical techniques in diagnosis and
      treatment over time, Chinese Thoracic Society of Chinese Medical Association
      updated its CAP guideline in 2016 to address the standard management of CAP in
      Chinese adults. Extensive and comprehensive literature search was made to collect
      the data and evidence for experts to review and evaluate the level of evidence.
      Corresponding recommendations are provided appropriately based on the level of
      evidence. This updated guideline covers comprehensive topics on CAP, including
      aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted
      treatments, adjunctive and supportive therapies, as well as prophylaxis. The
      recommendations may help clinicians manage CAP patients more effectively and
      efficiently. CAP in pediatric patients and immunocompromised adults is beyond the
      scope of this guideline. This guideline is only applicable for the
      immunocompetent CAP patients aged 18 years and older. The recommendations on
      selection of antimicrobial agents and the dosing regimens are not mandatory. The
      clinicians are recommended to prescribe and adjust antimicrobial therapies
      primarily based on their local etiological profile and results of susceptibility
      testing, with reference to this guideline.

PMID- 28756642
TI  - Factors influencing the quality of Myrmecia pilosula (Jack Jumper) ant venom for
      use in in vitro and in vivo diagnoses of allergen sensitization and in allergen
      immunotherapy.
AB  - BACKGROUND: Allergen immunotherapy uses pharmaceutical preparations derived from
      naturally occurring source materials, which contain water-soluble allergenic
      components responsible for allergic reactions. The success of in vivo and in
      vitro diagnoses in allergen sensitization and allergen immunotherapy largely
      depends on the quality, composition and uniformity of allergenic materials used
      to produce the active ingredients, and the formulation employed to prepare
      finished products. OBJECTIVES: We aimed to examine the factors influencing batch
      to-batch consistency of Jack Jumper (Myrmecia pilosula) ant venom (JJAV) in the
      form of active pharmaceutical ingredient (AI) and informed whether factors such
      as temperature, artificial light and container materials influence the quality of
      JJAV AIs. We also aimed to establish handling and storage requirements of JJAV
      AIs to ensure preservation of allergenic activities during usage in the diagnosis
      of allergen sensitization and in allergen immunotherapy. METHODS: The quality and
      consistency of JJAV AIs were analysed using a combination of bicinchoninic acid
      assay for total protein quantification, HPLC-UV for JJAV allergen peptides
      quantification, ELISA inhibition for total allergenic potency, SDS-PAGE, AU-PAGE
      and immunoblot for qualitative assessment of JJAV components, and Limulus
      Amebocyte Lysate assay for the quantification of endotoxin concentration. API-ZYM
      and Zymogram assays were used to probe the presence of enzymatic activities in
      JJAV. RESULTS: Pharmaceutical-grade JJAV for allergen immunotherapy has good
      batch-to-batch consistency. Temporary storage at 4 degrees C and light exposure
      do not affect the quality of JJAV. Exposure to temperature above 40 degrees C
      degrades high MW allergens in JJAV. Vials containing JJAV must be stored frozen
      and in upright position during long-term storage. CONCLUSIONS AND CLINICAL
      RELEVANCE: We have identified factors, which can influence the quality and
      consistency of JJAV AIs, and provided a framework for appropriate handling,
      transporting and storage of JJAV to be used for the diagnosis of allergen
      sensitization and in AIT.

PMID- 28756643
TI  - Commentary on Myths and Methodologies: Making sense of exercise mass and water
      balance.

PMID- 28756645
TI  - Performance of the Hack's Impairment Index Score: A Novel Tool to Assess
      Impairment from Alcohol in Emergency Department Patients.
AB  - BACKGROUND: Over 35 million alcohol-impaired (AI) patients are cared for in
      emergency departments (EDs) annually. Emergency physicians are charged with
      ensuring AI patients' safety by identifying resolution of alcohol-induced
      impairment. The most common standard evaluation is an extemporized clinical
      examination, as ethanol levels are not reliable or predictive of clinical
      symptoms. There is no standard assessment of ED AI patients. OBJECTIVE: The
      objective was to evaluate a novel standardized ED assessment of alcohol
      impairment, Hack's Impairment Index (HII score), in a busy urban ED. METHODS: A
      retrospective chart review was performed for all AI patients seen in our busy
      urban ED over 24 months. Trained nurses evaluated AI patients with both "usual"
      and HII score every 2 hours. Patients were stratified by frequency of visits for
      AI during this time: high (>= 6), medium (2-5), and low (1). Within each
      category, comparisons were made between HII scores, measured ethanol levels, and
      usual nursing assessment of AI. Changes in HII scores over time were also
      evaluated. RESULTS: A total of 8,074 visits from 3,219 unique patients were
      eligible for study, including 7,973 (98.7%) with ethanol levels, 5,061 (62.7%)
      with complete HII scores, and 3,646 (45.2%) with health care provider
      assessments. Correlations between HII scores and ethanol levels were poor
      (Pearson's R2  = 0.09, 0.09, and 0.17 for high-, medium-, and low-frequency
      strata). HII scores were excellent at discriminating nursing assessment of AI,
      while ethanol levels were less effective. Omitting extrema, HII scores fell
      consistently an average 0.062 points per hour, throughout patients' visits.
      CONCLUSIONS: The HII score applied a quantitative, objective assessment of
      alcohol impairment. HII scores were superior to ethanol levels as an objective
      clinical measure of impairment. The HII declines in a reasonably predictable
      manner over time, with serial evaluations corresponding well with health care
      provider evaluations.

PMID- 28756644
TI  - The role of anaplastic lymphoma kinase in pediatric cancers.
AB  - The anaplastic lymphoma kinase (ALK) gene was initially identified as a fusion
      partner of the nucleophosmin gene in anaplastic large-cell lymphoma with
      t(2;5)(p23;q35) translocation, and then described with different genetic
      abnormalities in a number of tumors. Although ALK is known to be involved in the
      pathogenesis of neuroblastoma through activating mutations or gene amplification,
      its role in the pathogenesis of other pediatric cancers is still elusive. In
      addition to neuroblastoma, the high-grade amplification of ALK has been described
      in a subset of rhabdomyosarcoma cases. Normal ALK protein expression is
      restricted to the nervous systems of adult mammals, but the aberrant expression
      of ALK has been observed in a variety of pediatric cancers, including glioma and
      Ewing sarcoma. The discovery of oncogenic activation of ALK in neuroblastoma
      suggests that this cancer could be potentially treated with an ALK inhibitor, as
      could other cancers, such as non-small-cell lung cancer and anaplastic large-cell
      lymphoma. However, cellular responses to mutant ALK are complex when compared to
      rearranged ALK, and treatment remains a challenge. This review focuses on the
      biology of ALK in pediatric cancers and possible therapeutic strategies for ALK
      associated tumors.

PMID- 28756646
TI  - Patient and Surrogate Views of Community Consultation for Emergency Research.
AB  - OBJECTIVE: Pretrial community consultation (CC) is required for emergency
      research conducted under an exception from informed consent (EFIC) in the United
      States. CC remains controversial and challenging, and minimal data exist
      regarding the views of individuals enrolled in EFIC trials on this process. It is
      important to know whether participants perceive CC to be meaningful and, if so,
      whom they believe should be consulted. METHODS: We conducted a secondary analysis
      of data from two studies interviewing patients and surrogates of two recent EFIC
      trials (PEER-RAMPART and PEER-ProTECT). These interviews included similar open-
      and closed-ended questions regarding participants' views of the importance of CC,
      the rationale for their responses, and their views regarding which populations
      should be included in consultation efforts. A template analytic strategy was used
      for qualitative analysis of textual data, and descriptive statistics were
      tabulated to characterize demographic data and instances of major themes.
      RESULTS: Ninety percent of participants perceived CC to be valuable.
      Participants' reasons for finding CC valuable clustered in two categories: 1) as
      a method of informing the public about the trial to be conducted and 2) as a way
      of obtaining input and feedback from the community. Participants cited the
      medical community (43%) and individuals with a connection to the study condition
      (41%) as the most important groups to involve in consultation efforts; only 5%
      suggested consulting the general public in the area where the research will be
      conducted. CONCLUSION: Participants in EFIC trials and their decision makers
      generally valued CC as a method of informing and seeking input from the
      community. Participants felt that the most appropriate groups to consult were the
      medical community and individuals with connections to the condition under study.
      Consultation efforts focused on these two groups, rather than the general public,
      may be more efficient and more meaningful to individuals involved in EFIC trials.
      These findings also reinforce the importance of the distinction between public
      disclosure and CC.

PMID- 28756648
TI  - Objective assessment of hearing during second stage of tympanoplasty-surgical
      technique and measurement methodology presented in ten patients.

PMID- 28756647
TI  - Mid-urethral sling operations for stress urinary incontinence in women.
AB  - BACKGROUND: Urinary incontinence is a very common and debilitating problem
      affecting about 50% of women at some point in their lives. Stress urinary
      incontinence (SUI) is a predominant cause in 30% to 80% of these women imposing
      significant health and economic burden on society and the women affected. Mid
      urethral sling (MUS) operations are a recognised minimally invasive surgical
      treatment for SUI. MUS involves the passage of a small strip of tape through
      either the retropubic or obturator space, with entry or exit points at the lower
      abdomen or groin, respectively. This review does not include single-incision
      slings. OBJECTIVES: To assess the clinical effects of mid-urethral sling (MUS)
      operations for the treatment of SUI, urodynamic stress incontinence (USI) or
      mixed urinary incontinence (MUI) in women. SEARCH METHODS: We searched: Cochrane
      Incontinence Specialised Register (including: CENTRAL, MEDLINE, MEDLINE In
      Process, ClinicalTrials.gov) (searched 26 June 2014); Embase Classic (January
      1947 to Week 25 2014); WHO ICTRP (searched 30 June 2014); reference lists.
      SELECTION CRITERIA: Randomised or quasi-randomised controlled trials amongst
      women with SUI, USI or MUI, in which both trial arms involve a MUS operation.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the
      methodological quality of potentially eligible studies and extracted data from
      included trials. MAIN RESULTS: We included 81 trials that evaluated 12,113 women.
      We assessed the quality of evidence for outcomes using the GRADE assessment tool;
      the quality of most outcomes was moderate, mainly due to risk of bias or
      imprecision.Fifty-five trials with data contributed by 8652 women compared the
      use of the transobturator route (TOR) and retropubic route (RPR). There is
      moderate quality evidence that in the short term (up to one year) the rate of
      subjective cure of TOR and RPR are similar (RR 0.98, 95% CI 0.96 to 1.00; 36
      trials, 5514 women; moderate quality evidence) ranging from 62% to 98% in the TOR
      group, and from 71% to 97% in the RPR group. Short-term objective cure was
      similar in the TOR and RPR groups (RR 0.98, 95% CI 0.96 to 1.00; 40 trials, 6145
      women). Fewer trials reported medium-term (one to five years) and longer-term
      (over five years) data, but subjective cure was similar between the groups (RR
      0.97, 95% CI 0.87 to 1.09; 5 trials, 683 women; low quality evidence; and RR
      0.95, 95% CI 0.80 to 1.12; 4 trials, 714 women; moderate quality evidence,
      respectively). In the long term, subjective cure rates ranged from 43% to 92% in
      the TOR group, and from 51% to 88% in the RPR group.MUS procedures performed
      using the RPR had higher morbidity when compared to TOR, though the overall rate
      of adverse events remained low. The rate of bladder perforation was lower after
      TOR (0.6% versus 4.5%; RR 0.13, 95% CI 0.08 to 0.20; 40 trials, 6372 women;
      moderate quality evidence). Major vascular/visceral injury, mean operating time,
      operative blood loss and length of hospital stay were lower with
      TOR.Postoperative voiding dysfunction was less frequent following TOR (RR 0.53,
      95% CI 0.43 to 0.65; 37 trials, 6200 women; moderate quality evidence). Overall
      rates of groin pain were higher in the TOR group (6.4% versus 1.3%; RR 4.12, 95%
      CI 2.71 to 6.27; 18 trials, 3221 women; moderate quality evidence) whereas
      suprapubic pain was lower in the TOR group (0.8% versus 2.9%; RR 0.29, 95% CI
      0.11 to 0.78); both being of short duration. The overall rate of vaginal tape
      erosion/exposure/extrusion was low in both groups: 24/1000 instances with TOR
      compared with 21/1000 for RPR (RR 1.13, 95% CI 0.78 to 1.65; 31 trials, 4743
      women; moderate quality evidence). There were only limited data to inform the
      need for repeat incontinence surgery in the long term, but it was more likely in
      the TOR group than in the RPR group (RR 8.79, 95% CI 3.36 to 23.00; 4 trials, 695
      women; low quality evidence).A retropubic bottom-to-top route was more effective
      than top-to-bottom route for subjective cure (RR 1.10, 95% CI 1.01 to 1.19; 3
      trials, 477 women; moderate quality evidence). It incurred significantly less
      voiding dysfunction, and led to fewer bladder perforations and vaginal tape
      erosions.Short-and medium-term subjective cure rates between transobturator tapes
      passed using a medial-to-lateral as opposed to a lateral-to-medial approach were
      similar (RR 1.00, 95% CI 0.96 to 1.06; 6 trials, 759 women; moderate quality
      evidence, and RR 1.06, 95% CI 0.91 to 1.23; 2 trials, 235 women; moderate quality
      evidence). There was moderate quality evidence that voiding dysfunction was more
      frequent in the medial-to-lateral group (RR 1.74, 95% CI 1.06 to 2.88; 8 trials,
      1121 women; moderate quality evidence), but vaginal perforation was less frequent
      in the medial-to-lateral route (RR 0.25, 95% CI 0.12 to 0.53; 3 trials, 541
      women). Due to the very low quality of the evidence, it is unclear whether the
      lower rates of vaginal epithelial perforation affected vaginal tape erosion (RR
      0.42, 95% CI 0.16 to 1.09; 7 trials, 1087 women; very low quality evidence).
      AUTHORS' CONCLUSIONS: Mid-urethral sling operations have been the most
      extensively researched surgical treatment for stress urinary incontinence (SUI)
      in women and have a good safety profile. Irrespective of the routes traversed,
      they are highly effective in the short and medium term, and accruing evidence
      demonstrates their effectiveness in the long term. This review illustrates their
      positive impact on improving the quality of life of women with SUI. However, a
      brief economic commentary (BEC) identified three studies suggesting that
      transobturator may be more cost-effective compared with retropubic. Fewer adverse
      events occur with employment of a transobturator approach with the exception of
      groin pain. When comparing transobturator techniques of a medial-to-lateral
      versus a lateral-to-medial insertion, there is no evidence to support the use of
      one approach over the other. However, a bottom-to-top route was more effective
      than top-to-bottom route for retropubic tapes.A salient point illustrated
      throughout this review is the need for reporting of longer-term outcome data from
      the numerous existing trials. This would substantially increase the evidence base
      and provide clarification regarding uncertainties about long-term effectiveness
      and adverse event profile.

PMID- 28756649
TI  - RNomic identification and evaluation of npcTB_6715, a non-protein-coding RNA gene
      as a potential biomarker for the detection of Mycobacterium tuberculosis.
AB  - Technological advances in RNA biology greatly improved transcriptome profiling
      during the last two decades. Besides the discovery of many small RNAs (sRNA) that
      are involved in the physiological and pathophysiological regulation of various
      cellular circuits, it becomes evident that the corresponding RNA genes might also
      serve as potential biomarkers to monitor the progression of disease and
      treatment. sRNA gene candidate npcTB_6715 was previously identified via
      experimental RNomic (unpublished data), and we report its application as
      potential biomarker for the detection of Mycobacterium tuberculosis (MTB) in
      patient samples. For proof of principle, we developed a multiplex PCR assay and
      report its validation with 500 clinical cultures, positive for Mycobacteria. The
      analysis revealed 98.9% sensitivity, 96.1% specificity, positive and negative
      predictive values of 98.6% and 96.8%, respectively. These results underscore the
      diagnostic value of the sRNA gene as diagnostic marker for the specific detection
      of MTB in clinical samples. Its successful application and the general ease of
      PCR-based detection compared to standard bacterial culture techniques might be
      the first step towards 'point-of-care' diagnostics of Mycobacteria. To the best
      of our knowledge, this is the first time for the design of diagnostic
      applications based on sRNA genes, in Mycobacteria.

PMID- 28756650
TI  - Accurate quantification of 5 German cockroach (GCr) allergens in complex extracts
      using multiple reaction monitoring mass spectrometry (MRM MS).
AB  - BACKGROUND: German cockroach (GCr) allergen extracts are complex and
      heterogeneous products, and methods to better assess their potency and
      composition are needed for adequate studies of their safety and efficacy.
      OBJECTIVE AND METHODS: The objective of this study was to develop an assay based
      on liquid chromatography and multiple reaction monitoring mass spectrometry (LC
      MRM MS) for rapid, accurate, and reproducible quantification of 5 allergens (Bla
      g 1, Bla g 2, Bla g 3, Bla g 4, and Bla g 5) in crude GCr allergen extracts.
      RESULTS: We first established a comprehensive peptide library of allergens from
      various commercial extracts as well as recombinant allergens. Peptide mapping was
      performed using high-resolution MS, and the peptide library was then used to
      identify prototypic and quantotypic peptides to proceed with MRM method
      development. Assay development included a systematic optimization of digestion
      conditions (buffer, digestion time, and trypsin concentration), chromatographic
      separation, and MS parameters. Robustness and suitability were assessed following
      ICH (Q2 [R1]) guidelines. The method is precise (RSD < 10%), linear over a wide
      range (r > 0.99, 0.01-1384 fmol/MUL), and sensitive (LLOD and LLOQ <1 fmol/MUL).
      Having established the parameters for LC-MRM MS, we quantified allergens from
      various commercial GCr extracts and showed considerable variability that may
      impact clinical efficacy. CONCLUSIONS AND CLINICAL RELEVANCE: Our data
      demonstrate that the LC-MRM MS method is valuable for absolute quantification of
      allergens in GCr extracts and likely has broader applicability to other complex
      allergen extracts. Definitive quantification provides a new standard for
      labelling of allergen extracts, which will inform patient care, enable
      personalized therapy, and enhance the efficacy of immunotherapy for environmental
      and food allergies.

PMID- 28756651
TI  - Relationship between driver gene mutations, their relative protein expressions
      and survival in non-small cell lung carcinoma in Macao.
AB  - OBJECTIVES: We report the status of most common gene mutations in non-small cell
      lung carcinoma (NSCLC) in Macao, and explore the relationship between each gene
      mutation and clinicopathologic features and survival. METHODS: EGFR, KRAS and
      BRAF mutations were detected by PCR in 122 cases of NSCLC. ALK translocation and
      MET amplification were detected by fluorescence in situ hybridization (FISH). MET
      and thyroid transcription factor (TTF-1) were investigated by
      immunohistochemistry. Clinical data were collected for analyzing their
      correlation with the gene mutations. RESULTS: The mutation of EGFR, KRAS and BRAF
      was detected in 48 (39.3%), 13 (10.7%) and 3 (2.5%) of 122 cases of NSCLC,
      respectively. ALK translocation and MET amplification were detected in 7 (5.7%)
      and 3 cases (2.5%). The rate of EGFR mutation was significantly higher in female
      and non-smoker patients. In TTF-1 positive cases EGFR mutation was more frequent.
      Age of the patients over 62-year old was correlated with KRAS mutations. The
      concordance between ALK IHC and FISH was 58.3%. The MET protein in the cases with
      MET amplification was 100% positive. The survival was lower in the patients with
      positive MET protein than those with negative. MET protein was an independent
      prognostic factor for NSCLC. CONCLUSIONS: EGFR mutation occurred frequently in
      the female never smoke patients with NSCLC. KRAS mutation was more common in old
      patients. Negative MET protein expression could be used as a negative predictive
      marker of MET amplification. MET protein expression was an independent prognostic
      factor for NSCLC.

PMID- 28756652
TI  - Iatrogenic Gastric Pseudolipomatosis during Endoscopic Submucosal Dissection.

PMID- 28756653
TI  - miR-23a Regulates Cardiomyocyte Apoptosis by Targeting Manganese Superoxide
      Dismutase.
AB  - Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated
      cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive
      reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide
      dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS
      into harmless products. In this study, we demonstrate that MnSOD is down
      regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury.
      Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial
      infarction induced by I/R injury. Further, we show that miR-23a directly
      regulates the expression of MnSOD. miR-23a regulates cardiomyocyte apoptosis by
      suppressing the expression of MnSOD. Our study reveals a novel model regulating
      cardiomyocyte apoptosis which is composed of miR-23a and MnSOD. Our study
      provides a new method to tackling apoptosis related cardiac diseases.

PMID- 28756654
TI  - Adverse Effect of Superovulation Treatment on Maturation, Function and
      Ultrastructural Integrity of Murine Oocytes.
AB  - Regular monitoring on experimental animal management found the fluctuation of ART
      outcome, which showed a necessity to explore whether superovulation treatment is
      responsible for such unexpected outcome. This study was subsequently conducted to
      examine whether superovulation treatment can preserve ultrastructural integrity
      and developmental competence of oocytes following oocyte activation and embryo
      culture. A randomized study using mouse model was designed and in vitro
      development (experiment 1), ultrastructural morphology (experiment 2) and
      functional integrity of the oocytes (experiment 3) retrieved after PMSG/hCG
      injection (superovulation group) or not (natural ovulation; control group) were
      evaluated. In experiment 1, more oocytes were retrieved following superovulation
      than following natural ovulation, but natural ovulation yielded higher (p <
      0.0563) maturation rate than superovulation. The capacity of mature oocytes to
      form pronucleus and to develop into blastocysts in vitro was similar. In
      experiment 2, a notable (p < 0.0186) increase in mitochondrial deformity,
      characterized by the formation of vacuolated mitochondria, was detected in the
      superovulation group. Multivesicular body formation was also increased, whereas
      early endosome formation was significantly decreased. No obvious changes in other
      microorganelles, however, were detected, which included the formation and
      distribution of mitochondria, cortical granules, microvilli, and smooth and rough
      endoplasmic reticulum. In experiment 3, significant decreases in mitochondrial
      activity, ATP production and dextran uptake were detected in the superovulation
      group. In conclusion, superovulation treatment may change both maturational
      status and functional and ultrastuctural integrity of oocytes. Superovulation
      effect on preimplantation development can be discussed.

PMID- 28756655
TI  - The Arabidopsis Phytocystatin AtCYS5 Enhances Seed Germination and Seedling
      Growth under Heat Stress Conditions.
AB  - Phytocystatins (PhyCYSs) are plant-specific proteinaceous inhibitors that are
      implicated in protein turnover and stress responses. Here, we characterized a
      PhyCYS from Arabidopsis thaliana, which was designated AtCYS5. RT-qPCR analysis
      showed that the expression of AtCYS5 in germinating seeds was induced by heat
      stress (HS) and exogenous abscisic acid (ABA) treatment. Analysis of the
      expression of the beta-glucuronidase reporter gene under the control of the
      AtCYS5 promoter showed that AtCYS5 expression during seed germination was induced
      by HS and ABA. Constitutive overexpression of AtCYS5 driven by the cauliflower
      mosaic virus 35S promoter led to enhanced HS tolerance in transgenic Arabidopsis,
      which was characterized by higher fresh weight and root length compared to wild
      type (WT) and knockout (cys5) plants grown under HS conditions. The HS tolerance
      of At-CYS5-overexpressing transgenic plants was associated with increased
      insensitivity to exogenous ABA during both seed germination and post-germination
      compared to WT and cys5. Although no HS elements were identified in the 5'
      flanking region of AtCYS5, canonical ABA-responsive elements (ABREs) were
      detected. AtCYS5 was upregulated in ABA-treated protoplasts transiently co
      expressing this gene and genes encoding bZIP ABRE-binding factors (ABFs and
      AREB3). In the absence of ABA, ABF1 and ABF3 directly bound to the ABREs in the
      AtCYS5 promoter, which activated the transcription of this gene in the presence
      of ABA. These results suggest that an ABA-dependent pathway plays a positive role
      in the HS-responsive expression of AtCYS5 during seed germination and post
      germination growth.

PMID- 28756656
TI  - Targeting Fatty-Acid Amide Hydrolase with Prodrugs for CNS-Selective Therapy.
AB  - The blood-brain barrier (BBB) can be a substantial impediment to achieving
      therapeutic levels of drugs in the CNS. Certain chemical functionality such as
      the carboxylic acid is a general liability for BBB permeability preventing
      significant CNS distribution of a drug from a systemic dose. Here, we report a
      strategy for CNS-selective distribution of the carboxylic acid containing
      thyromimetic sobetirome using prodrugs targeted to fatty-acid amide hydrolase
      (FAAH), which is expressed in the brain. Two amide prodrugs of sobetirome were
      shown to be efficient substrates of FAAH with Vmax/KM values comparable to the
      natural endocannabinoid FAAH substrate anandamide. In mice, a systemic dose of
      sobetirome prodrug leads to a substantial ~60-fold increase in brain distribution
      (Kp) of sobetirome compared to an equimolar systemic dose of the parent drug. The
      increased delivery of sobetirome to the brain from the prodrug was diminished by
      both pharmacological inhibition and genetic deletion of FAAH in vivo. The
      increased brain exposure of sobetirome arising from the prodrug corresponds to
      ~30-fold increased potency in brain target engagement compared to the parent
      drug. These results suggest that FAAH-targeted prodrugs can considerably increase
      drug exposure to the CNS with a concomitant decrease in systemic drug levels
      generating a desirable distribution profile for CNS acting drugs.

PMID- 28756657
TI  - Versatile Separation and Analysis of Heparan Sulfate Oligosaccharides Using
      Graphitized Carbon Liquid Chromatography and Electrospray Mass Spectrometry.
AB  - Heparin and heparan sulfate (HS) by nature contain multiple isomeric structures,
      which are fundamental for the regulation of biological processes. Here we report
      the use of a porous graphitized carbon (PGC) LC-MS method with effective
      separation and sensitivity to separate mixtures of digested HS oligosaccharides.
      Application of this method allowed the separation of oligosaccharide mixtures
      with various degree of polymerization (dp) ranging from dp4 to dp8, two dp4
      isomers that were baseline resolved, four dp6 isomers, and the observation of a
      dp3 oligosaccharide. PGC LC-MS of complex mixtures demonstrated that compounds
      eluted from the column in decreasing order of hydrophilicity, with the more
      highly sulfated structures eluting first. Our data indicate that sulfation
      levels, chain length, and conformation all effect elution order. We found that
      PGC's resolving capabilities for the dp4 and dp6 isomeric structures makes this
      methodology particularly useful for the sequencing of HS saccharides, because the
      lack of contaminating isomeric structures provides unambiguous structural
      assignments from the MS/MS data. Collectively this work demonstrates that PGC
      column-based methods are powerful tools for enhanced separation and analysis of
      heterogeneous mixtures of HS saccharide species.

PMID- 28756659
TI  - Fluorine- and Nitrogen-Codoped MoS2 with a Catalytically Active Basal Plane.
AB  - Two-dimensional molybdenum disulfide (2D MoS2) has drawn persistent interests as
      one of the most promising alternatives to Pt catalysts for the hydrogen evolution
      reaction (HER). It is generally accepted that the edge sites of 2D MoS2 are
      catalytically active but the basal planes are inert. Activating the MoS2 basal
      plane is an obvious strategy to enhance the HER activity of this material.
      However, few approaches have sought to activate the basal plane. Here, for the
      first time, we demonstrate that the inert basal planes can be activated via the
      synergistic effects of nitrogen and fluorine codoping. Our first-principles
      calculations reveal that nitrogen in the basal plane of the fluorine- and
      nitrogen-codoped MoS2 (NF-MoS2) can act as a new active and further tuneable
      catalytic site. The as-prepared NF-MoS2 catalyst exhibited an enormously enhanced
      HER activity compared to that of pure MoS2 and N-doped MoS2 due to the chemical
      codoping effect. This work will pave a novel pathway for enhancing the HER
      activity using the synergistic effects of chemical codoping.

PMID- 28756660
TI  - Spectroscopy and DFT Calculations of a Flavo-diiron Enzyme Implicate New Diiron
      Site Structures.
AB  - Flavo-diiron proteins (FDPs) are non-heme iron containing enzymes that are
      widespread in anaerobic bacteria, archaea, and protozoa, serving as the terminal
      components to dioxygen and nitric oxide reductive scavenging pathways in these
      organisms. FDPs contain a dinuclear iron active site similar to that in
      hemerythrin, ribonucleotide reductase, and methane monooxygenase, all of which
      can bind NO and O2. However, only FDP competently turns over NO to N2O. Here, EPR
      and Mossbauer spectroscopies allow electronic characterization of the diferric
      and diferrous species of FDP. The exchange-coupling constant J (Hex = JS1.S2) was
      found to increase from +20 cm-1 to +32 cm-1 upon reduction of the diferric to the
      diferrous species, indicative of (1) at least one hydroxo bridge between the iron
      ions for both states and (2) a change to the diiron core structure upon
      reduction. In comparison to characterized diiron proteins and synthetic
      complexes, the experimental values were consistent with a dihydroxo bridged
      diferric core, which loses one hydroxo bridge upon reduction. DFT calculations of
      these structures gave values of J and Mossbauer parameters in agreement with
      experiment. Although the crystal structure shows a hydrogen bond between the iron
      bound aspartate and the bridging solvent molecule, the DFT calculations of
      structures consistent with the crystal structure gave calculated values of J
      incompatible with the spectroscopic results. We conclude that the crystal
      structure of the diferric state does not represent the frozen solution structure
      and that a mono-MU-hydroxo diferrous species is the catalytically functional
      state that reacts with NO and O2. The new EPR spectroscopic probe of the diferric
      state indicated that the diferric structure of FDP prior to and immediately after
      turnover with NO are flavin mononucleotide (FMN) dependent, implicating an
      additional proton transfer role for FMN in turnover of NO.

PMID- 28756661
TI  - Boron Switch for Selectivity of Catalytic Dehydrogenation on Size-Selected Pt
      Clusters on Al2O3.
AB  - Size-selected supported clusters of transition metals can be remarkable and
      highly tunable catalysts. A particular example is Pt clusters deposited on
      alumina, which have been shown to dehydrogenate hydrocarbons in a size-specific
      manner. Pt7, of the three sizes studied, is the most active and, therefore, like
      many other catalysts, deactivates by coking during reactions in hydrocarbon-rich
      environments. Using a combination of experiment and theory, we show that
      nanoalloying Pt7 with boron modifies the alkene-binding affinity to reduce
      coking. From a fundamental perspective, the comparison of experimental and
      theoretical results shows the importance of considering not simply the most
      stable cluster isomer, but rather the ensemble of accessible structures as it
      changes in response to temperature and reagent coverage.

PMID- 28756662
TI  - Rh(III)-Catalyzed C-H Cyclization of Arylnitrones with Diazo Compounds: Access to
      3-Carboxylate Substituted N-Hydroxyindoles.
AB  - Recently, N-hydroxyindole derivatives have received much interest because of
      their unique structural motif and various biological activities. In this study,
      we report the first example of a Rh(III)-catalyzed reaction of arylnitrones with
      alpha-diazoketoesters or alpha-diazodiketones to produce N-hydroxyindole
      derivatives. Intriguingly, we could build the N-hydroxyindole scaffold by
      blocking the cleavage of the N-O bond selectively, while eliminating the acyl
      group of alpha-diazoketoesters or alpha-diazodiketones preferentially.

PMID- 28756658
TI  - Polymers for 3D Printing and Customized Additive Manufacturing.
AB  - Additive manufacturing (AM) alias 3D printing translates computer-aided design
      (CAD) virtual 3D models into physical objects. By digital slicing of CAD, 3D
      scan, or tomography data, AM builds objects layer by layer without the need for
      molds or machining. AM enables decentralized fabrication of customized objects on
      demand by exploiting digital information storage and retrieval via the Internet.
      The ongoing transition from rapid prototyping to rapid manufacturing prompts new
      challenges for mechanical engineers and materials scientists alike. Because
      polymers are by far the most utilized class of materials for AM, this Review
      focuses on polymer processing and the development of polymers and advanced
      polymer systems specifically for AM. AM techniques covered include vat
      photopolymerization (stereolithography), powder bed fusion (SLS), material and
      binder jetting (inkjet and aerosol 3D printing), sheet lamination (LOM),
      extrusion (FDM, 3D dispensing, 3D fiber deposition, and 3D plotting), and 3D
      bioprinting. The range of polymers used in AM encompasses thermoplastics,
      thermosets, elastomers, hydrogels, functional polymers, polymer blends,
      composites, and biological systems. Aspects of polymer design, additives, and
      processing parameters as they relate to enhancing build speed and improving
      accuracy, functionality, surface finish, stability, mechanical properties, and
      porosity are addressed. Selected applications demonstrate how polymer-based AM is
      being exploited in lightweight engineering, architecture, food processing,
      optics, energy technology, dentistry, drug delivery, and personalized medicine.
      Unparalleled by metals and ceramics, polymer-based AM plays a key role in the
      emerging AM of advanced multifunctional and multimaterial systems including
      living biological systems as well as life-like synthetic systems.

PMID- 28756663
TI  - Design and Characterization of an Electrically Powered Single Molecule on Gold.
AB  - The surface diffusion of individual molecules is of paramount importance in self
      assembly processes and catalytic processes. However, the fundamental
      understanding of molecule diffusion peculiarities considering conformations and
      adsorption sites remain poorly known at the atomic scale. Here, we probe the 4'
      (4-tolyl)-2,2':6',2"-terpyridine adsorbed on the Au(111) herringbone structure
      combining scanning tunneling microscopy and atomic force microscopy. Molecules
      are controllably translated by electrons excitations over the reconstruction,
      except at elbows acting as pinning centers. Experimental data supported by
      theoretical calculations show the formation of coordination bonds between the
      molecule and Au atoms of the surface. Using force spectroscopy, we quantify local
      variation of the surface potential and the lateral force required to move the
      molecule. We found an elevation of the diffusion barrier at elbows of the
      reconstruction of ~100 meV compared to the rest of the surface.

PMID- 28756665
TI  - Temperature Programming of the Second Dimension in Comprehensive Two-Dimensional
      Gas Chromatography.
AB  - Comprehensive two-dimensional gas chromatography (GC * GC) provides a significant
      increase in selectivity and peak capacity for the separation of complex mixtures.
      Optimization of the system is often complicated, with many interconnected
      parameters between the two dimensions and additional problems like peak
      wraparound that need to be eliminated or minimized. Wraparound peaks are
      compounds with retention times in the second dimension that are longer than the
      modulation period. This results in broad peaks that elute in subsequent
      modulation cycles, potentially coeluting with separated compounds. The use of a
      secondary oven is often the solution to the problem. By applying a constant
      positive temperature offset from the main oven temperature, the retention of all
      analytes can be reduced so that they elute within their respective modulation
      periods. However, this reduces the separation of less retained compounds, a
      classical consequence of the general elution problem due to the isothermal
      conditions during the limited separation time in the second dimension. To
      overcome this problem, the second dimension was temperature-programmed by
      resistively heating an electrically conductive secondary column using constant
      current. The column was cooled through forced convection inside the GC oven
      within the time frame of a single modulation period. Temperature programming in
      the second dimension of GC * GC was able to improve separation while eliminating
      wraparound peaks and reducing peak widths, leading to significantly increased
      second dimension peak capacity.

PMID- 28756666
TI  - Universal Nanopatterning Technique Combining Secondary Sputtering with Nanoscale
      Electroplating for Fabricating Size-Controllable Ultrahigh-Resolution
      Nanostructures.
AB  - Here, we describe a next-generation lithographic technique for fabricating
      ultrahigh-resolution nanostructures. This technique makes use of the secondary
      sputtering phenomenon of plasma ion etching and of nanoscale electroplating to
      finely control the resolution of the fabricated structures from ten nanometers to
      hundreds of nanometers from a single microsized master pattern. In contrast to
      previously described techniques that incorporate a recently developed secondary
      sputtering lithography (SSL) patterning approach, which could only yield 10 nm
      resolution structures, in the current technique, we used an improved SSL approach
      to produce various-sized, high-resolution structures. Additionally, this improved
      SSL approach was used to fabricate size-controllable 3D patterns on various types
      of substrates, in particular, a silicon wafer, transparent glass, and flexible
      polycarbonate (PC) film. Thus, this method can serve as a new-concept patterning
      method for the efficient mass production of ultrahigh-resolution nanostructures.

PMID- 28756664
TI  - Structural and Functional Survey of Environmental Aminoglycoside
      Acetyltransferases Reveals Functionality of Resistance Enzymes.
AB  - Aminoglycoside N-acetyltransferases (AACs) confer resistance against the clinical
      use of aminoglycoside antibiotics. The origin of AACs can be traced to
      environmental microbial species representing a vast reservoir for new and
      emerging resistance enzymes, which are currently undercharacterized. Here, we
      performed detailed structural characterization and functional analyses of four
      metagenomic AAC (meta-AACs) enzymes recently identified in a survey of
      agricultural and grassland soil microbiomes ( Forsberg et al. Nature 2014 , 509 ,
      612 ). These enzymes are new members of the Gcn5-Related-N-Acetyltransferase
      superfamily and confer resistance to the aminoglycosides gentamicin C, sisomicin,
      and tobramycin. Moreover, the meta-AAC0020 enzyme demonstrated activity
      comparable with an AAC(3)-I enzyme that serves as a model AAC enzyme identified
      in a clinical bacterial isolate. The crystal structure of meta-AAC0020 in complex
      with sisomicin confirmed an unexpected AAC(6') regiospecificity of this enzyme
      and revealed a drug binding mechanism distinct from previously characterized
      AAC(6') enzymes. Together, our data highlights the presence of highly active
      antibiotic-modifying enzymes in the environmental microbiome and reveals
      unexpected diversity in substrate specificity. These observations of additional
      AAC enzymes must be considered in the search for novel aminoglycosides less prone
      to resistance.

PMID- 28756668
TI  - Synthesis of 2-Aryl-5-alkyl-fulleropyrrolidines: Metal-Free-Mediated Reaction of
      [60]Fullerene with Aromatic Aldehydes and Inactive Primary Amines.
AB  - The metal-free-mediated thermal reaction of [60]fullerene with aromatic aldehydes
      and inactive primary amines bearing electron-donating groups at the alpha
      position afforded a series of 2-aryl-5-alkyl-fulleropyrrolidines, including the
      scarce 2-aryl-5-benzyl-fulleropyrrolidines as a mixture of cis and trans isomers.
      With rare exceptions, the mixture of cis and trans isomers could be easily
      isolated by column chromatography, with a preference of cis isomers as major
      products. A plausible mechanism for the formation of fulleropyrrolidines is also
      proposed.

PMID- 28756669
TI  - High-Level Quantum Calculations of the IR Spectra of the Eigen, Zundel, and Ring
      Isomers of H+(H2O)4 Find a Single Match to Experiment.
AB  - The protonated water tetramer H+(H2O)4, often written as the Eigen cluster,
      H3O+(H2O)3, plays a central role in studies of the hydrated proton. The cluster
      has been investigated spectroscopically both experimentally and theoretically
      with some differences and controversies. The major issue stems from the existence
      of higher-energy Zundel isomers of this cluster and the role these isomers might
      play in the IR spectra. Settling this fundamental issue is one goal of this
      Communication, where high-level quantum calculations of the IR spectra of the
      Eigen and three isomeric forms of this cluster are presented. These calculations
      make use of a many-body representation of the potential and dipole moment
      surfaces and VSCF/VCI calculations of vibrational eigenstates and the IR
      spectrum. The calculated spectra for the Eigen H3O+(H2O)3 and D3O+(D2O)3 isomers
      compare very well with experiment. The calculated spectra for the cis and trans
      Zundel and ring isomers show prominent features that do not match with experiment
      but which can guide future experiments to search for these interesting and
      important isomers.

PMID- 28756670
TI  - Cholesterol-Appended Benzimidazolium Salts: Synthesis, Aggregation, Sensing, Dye
      Adsorption, and Semiconducting Properties.
AB  - A series of cholesterol-appended benzimidazolium salts 1-9 have been designed and
      synthesized. They have been explored in gel chemistry. The gelation of the
      benzimidazolium salts is dependent on the nature of the counteranions. In
      addition, the gelation behavior of the gelators is linked with the presence of
      both pi-stacking and cholesteryl motifs. Whereas bisbenzimidazolium salt 2 forms
      a gel in dimethylsulfoxide/H2O (1:1, v/v) itself, under similar conditions,
      monobenzimidazolium salts 4 and 6 exhibit gelation in the presence of F- ions and
      validate the visual sensing of F-. As an application, the gel phase of 2
      efficiently removes toxic dyes from waste water. Furthermore, all gels show
      thermally activated semiconducting property within a wide voltage window.

PMID- 28756671
TI  - Tocopherols, Tocomonoenols, and Tocotrienols in Oils of Costa Rican Palm Fruits:
      A Comparison between Six Varieties and Chemical versus Mechanical Extraction.
AB  - Palm oil is one of the richest sources of tocotrienols and may contain other non
      tocopherol vitamin E congeners. The vitamin E profiles of fully ripened fruit
      mesocarp of three Elaeis guineensis, two Elaeis oleifera, and one hybrid O * G
      palm fruit genotypes from Costa Rica were analyzed by high-performance liquid
      chromatography with fluorescence detection and gas chromatography-mass
      spectrometry after mechanical extraction by a screw press and chemical extraction
      with hexane. gamma-Tocotrienol, alpha-tocotrienol, and alpha-tocopherol were the
      most abundant tocochromanols, while other tocopherols (beta-tocopherol, gamma
      tocopherol, and delta-tocopherol) and alpha-tocomonoenol were detected at minor
      concentrations. Significant differences in vitamin E profiles between genotypes
      were observed, and the variety E. oleifera Quepos (CB9204) had by far the highest
      content of total tocotrienols (890 MUg/g of oil) and total vitamin E (892 MUg/g
      of oil). Chemical extraction with hexane afforded up to 2.5-fold higher vitamin E
      yields than screw press extraction. alpha-Tocomonoenol co-eluted with gamma
      tocopherol in reversed-phase high-performance liquid chromatography analyses and
      is a possible source of error in the quantification of gamma-tocopherol in foods.

PMID- 28756672
TI  - Unveiling the Interaction between Fatty-Acid-Modified Membrane and Hydrophilic
      Imidazolium-Based Ionic Liquid: Understanding the Mechanism of Ionic Liquid
      Cytotoxicity.
AB  - Ionic liquids (ILs) are considered as "green solvents" for more than 2 decades.
      However, recent studies suggest that some ILs exhibit greater toxicity compared
      to common solvents. As a proactive effort to better understand the molecular
      origin of the cytotoxicity, the work herein presents the systemic
      characterization of the interaction between model membrane composed of fatty
      acids and popular imidazolium-based hydrophilic IL. The fusion kinetics between
      the vesicles demonstrates the swelling of the vesicle. Further, membrane fluidity
      is determined using the isomerization kinetics of a lipophilic dye, merocyanine
      540, and in the presence of IL, the fluidity of the inner water pool of the
      vesicle is increased. The results can be directly correlated to the cytotoxicity
      generated by IL in K562 cell, a human erythroleukemic cell line. High
      concentration IL ruptures the cell membrane and causes membrane permeabilization.
      Thus, the results would help to facilitate the rational design of nontoxic ILs.

PMID- 28756673
TI  - Evolution of Volatile Compounds during the Distillation of Cognac Spirit.
AB  - Cognac wine spirit has a complex composition in volatile compounds which
      contributes to its organoleptic profile. This work focused on the batch
      distillation process and, in particular, on volatile compounds specifically
      produced by chemical reactions during the distillation of Cognac wine spirit,
      traditionally conducted in two steps with charentais pot stills. The aim of this
      study was to characterize these volatile compounds formed during distillation.
      Sampling has been performed on the distillates and inside the boiler during a
      typical Cognac distillation. The analysis of these samples allowed us to perform
      a mass balance and to point out several types of volatile compounds whose
      quantities strongly increased during the distillation process. These compounds
      were distinguished by their chemical family. It has been found that the first
      distillation step was decisive for the formation of volatile compounds. Moreover,
      2 esters, 3 aldehydes, 12 norisoprenoids, and 3 terpenes were shown to be
      generated during the process. These results suggest that some volatile compounds
      found in Cognac spirit are formed during distillation due to chemical reactions
      induced by high temperature. These findings give important indications to
      professional distillers in order to enhance the product's quality.

PMID- 28756674
TI  - Correction to "A New "Quasi-Dynamic" Method for Determining the Hamaker Constant
      of Solids using an Atomic Force Microscope".

PMID- 28756675
TI  - Trees and Streets as Drivers of Urban Stormwater Nutrient Pollution.
AB  - Expansion of tree cover is a major management goal in cities because of the
      substantial benefits provided to people, and potentially to water quality through
      reduction of stormwater volume by interception. However, few studies have
      addressed the full range of potential impacts of trees on urban runoff, which
      includes deposition of nutrient-rich leaf litter onto streets connected to storm
      drains. We analyzed the influence of trees on stormwater nitrogen and phosphorus
      export across 19 urban watersheds in Minneapolis-St. Paul, MN, U.S.A., and at the
      scale of individual streets within one residential watershed. Stormwater nutrient
      concentrations were highly variable across watersheds and strongly related to
      tree canopy over streets, especially for phosphorus. Stormwater nutrient loads
      were primarily related to road density, the dominant control over runoff volume.
      Street canopy exerted opposing effects on loading, where elevated nutrient
      concentrations from trees near roads outweighed the weak influence of trees on
      runoff reduction. These results demonstrate that vegetation near streets
      contributes substantially to stormwater nutrient pollution, and therefore to
      eutrophication of urban surface waters. Urban landscape design and management
      that account for trees as nutrient pollution sources could improve water quality
      outcomes, while allowing cities to enjoy the myriad benefits of urban forests.

PMID- 28756676
TI  - Stabilizing Cesium Lead Halide Perovskite Lattice through Mn(II) Substitution for
      Air-Stable Light-Emitting Diodes.
AB  - All-inorganic cesium lead halide perovskite (CsPbX3, X = Cl, Br, and I) quantum
      dots (QDs), possessing high photoluminescence quantum yields and tunable color
      output, have recently been endowed great promise for high-performance solar cells
      and light-emitting diodes (LEDs). Although moisture stability has been greatly
      improved through separating QDs with a SiO2 shell, the practical applications of
      CsPbX3 QDs are severely restricted by their poor thermal stability, which is
      associated with the intrinsically low formation energies of perovskite lattices.
      In this regard, enhancing the formation energies of perovskite lattices of CsPbX3
      QDs holds great promise in getting to the root of their poor thermal stability,
      which hitherto remains untouched. Herein, we demonstrate an effective strategy
      through Mn2+ substitution to fundamentally stabilize perovskite lattices of
      CsPbX3 QDs even at high temperatures up to 200  degrees C under ambient air
      conditions. We employ first-principle calculations to confirm that the
      significantly improved thermal stability and optical performance of CsPbX3:Mn2+
      QDs arise primarily from the enhanced formation energy due to the successful
      doping of Mn2+ in CsPbX3 QDs. Benefiting from such an effective substitution
      strategy, these Mn2+-doped CsPbX3 QDs can function well as efficient light
      emitters toward the fabrication of high-performance perovskite LEDs.

PMID- 28756677
TI  - Effect of a Co-Based Oxygen-Evolving Catalyst on TiO2-Photocatalyzed Organic
      Oxidation.
AB  - Cobalt phosphate (CoPi) is a promising cocatalyst for the (photo)electrochemical
      oxidation of water over semiconductor electrodes in phosphate solution, but the
      effect of CoPi on organic oxidation reactions has been little studied. Herein, we
      report a compound-sensitive effect of CoPi on the TiO2-photocatalyzed oxidation
      of phenol, 4-chlorophenol (CP), and 2,4-dichlorophenol (DCP) in a phosphate
      containing suspension at pH 7.0. A photochemical method was used to deposit Pt
      onto TiO2 and then CoPi onto both Pt/TiO2 and TiO2. In all reactions, Pt/TiO2 and
      CoPi/TiO2 were always more active and less active, respectively, than TiO2. In
      comparison with Pt/TiO2, CoPi/Pt/TiO2 was less active for phenol oxidation but
      more active for CP and DCP oxidation. CoPi/Pt/TiO2 was also more active than
      Pt/TiO2 for the photocatalytic reduction of O2 into H2O2. For DCP oxidation in a
      phosphate-free suspension at pH 7, however, CoPi/Pt/TiO2 was much less active
      than either Pt/TiO2 or TiO2, which is ascribed to the dissolution of Co2+ ions
      that act as recombination centers. It is proposed that the CoIV species, formed
      by the hole oxidation of CoII/III in CoPi, are surface-bound and short-lived.
      They can react with a nearby adsorbed substrate (CP, DCP, and H2O2) but
      deactivate in the absence of either Pt (O2 reduction catalyst) or phosphate (CoPi
      repairer). Moreover, there is a synergism between the CoPi-mediated hole transfer
      and the Pt-mediated electron transfer, that improves the efficiency of the charge
      separation and, consequently, increases the rates of O2 reduction and organic
      oxidation.

PMID- 28756678
TI  - A comparative analysis of policies addressing rural oral health in eight English
      speaking OECD countries.
AB  - INTRODUCTON: Oral health is fundamental to overall health. Poor oral health is
      largely preventable but unacceptable inequalities exist, particularly for people
      in rural areas. The issues are complex. Rural populations are characterised by
      lower rates of health insurance, higher rates of poverty, less water
      fluoridation, fewer dentists and oral health specialists, and greater distances
      to access care. These factors inter-relate with educational, attitudinal, and
      system-level issues. An important area of enquiry is whether and how national
      oral health policies address causes and solutions for poor rural oral health. The
      purpose of this study was to examine a series of government policies on oral
      health to (i) determine the extent to which such policies addressed rural oral
      health issues, and (ii) identify enabling assumptions in policy language about
      problems and solutions regarding rural communities. METHODS: Eight current oral
      health policies were identified from Australia, New Zealand, Canada, the USA,
      England, Scotland, Northern Ireland, and Wales. Validated content and critical
      discourse analyses were used to document and explore the concepts in these policy
      documents, with a particular focus on the frequency with which rural oral health
      was mentioned, and the enabling assumptions in policy language about rural
      communities. RESULTS: Seventy-three concepts relating to oral health were
      identified from the textual analysis of the eight policy documents. The rural
      concept addressing oral health issues occurred in only 2% of all policies and was
      notably absent from the oral health policies of countries with substantial rural
      populations. It occurred most frequently in the policy documents from Australia
      and Scotland, less so in the policy documents from Canada, Wales, and New
      Zealand, and not at all in the oral health policies from the US, England, and
      Northern Ireland. Thus, the oral health needs of rural communities were generally
      not the focus of, nor included in, the oral health policy documents in this
      study. When the language of concepts related to rural oral health was examined,
      the qualitative analysis identified four discourse themes related to both
      causality and solutions. These ranked discourse themes focused on service models,
      workforce issues, social determinants of health, and prevention. None of the
      policies addressed the structural economic determinants of unequal rural oral
      health, nor did they specifically assert the rights of children in rural
      communities to equitable oral health care. CONCLUSIONS: This study documented the
      limited focus on rural oral health that existed in national oral health policies
      from eight different English-speaking countries. It supports the need for an
      increased focus on rural oral health issues in oral health policies, particularly
      as increased oral health is clearly associated with increased general health. It
      speaks to the critical importance of periodic analysis of the content of oral
      health policies to ensure that issues of inequality are addressed. Further, it
      reinforces the need for research findings about effective oral health care to be
      translated into practice in the development of practical and financially viable
      policies to make access to oral health care more equitable, particularly for
      people living in rural and remote areas.

PMID- 28756679
TI  - Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in
      paracetamol overdose treated with a 2-bag acetylcysteine regimen.
AB  - INTRODUCTION: Paracetamol concentration is a highly accurate risk predictor for
      hepatotoxicity following overdose with known time of ingestion. However, the
      paracetamol-aminotransferase multiplication product can be used as a risk
      predictor independent of timing or ingestion type. Validated in patients treated
      with the traditional, "three-bag" intravenous acetylcysteine regimen, we
      evaluated the accuracy of the multiplication product in paracetamol overdose
      treated with a two-bag acetylcysteine regimen. METHODS: We examined consecutive
      patients treated with the two-bag regimen from five emergency departments over a
      two-year period. We assessed the predictive accuracy of initial multiplication
      product for the primary outcome of hepatotoxicity (peak alanine aminotransferase
      >=1000IU/L), as well as for acute liver injury (ALI), defined peak alanine
      aminotransferase >=2* baseline and above 50IU/L). RESULTS: Of 447 paracetamol
      overdoses treated with the two-bag acetylcysteine regimen, 32 (7%) developed
      hepatotoxicity and 73 (16%) ALI. The pre-specified cut-off points of 1500 mg/L *
      IU/L (sensitivity 100% [95% CI 82%, 100%], specificity 62% [56%, 67%]) and 10,000
      mg/L * IU/L (sensitivity 70% [47%, 87%], specificity of 97% [95%, 99%]) were
      highly accurate for predicting hepatotoxicity. There were few cases of
      hepatotoxicity irrespective of the product when acetylcysteine was administered
      within eight hours of overdose, when the product was largely determined by a high
      paracetamol concentration but normal aminotransferase. CONCLUSIONS: The
      multiplication product accurately predicts hepatotoxicity when using a two-bag
      acetylcysteine regimen, especially in patients treated more than eight hours post
      overdose. Further studies are needed to assess the product as a method to adjust
      for exposure severity when testing efficacy of modified acetylcysteine regimens.

PMID- 28756680
TI  - Correction to: Toce et al., A case report of methadone-associated hypoglycemia in
      an 11-month-old male.

PMID- 28756681
TI  - Explicit and implicit motor learning in children with unilateral cerebral palsy.
AB  - OBJECTIVES: The current study aimed to investigate the capacity for explicit and
      implicit learning in children with unilateral cerebral palsy. PARTICIPANTS:
      Children with left and right unilateral cerebral palsy and typically developing
      children shuffled disks toward a target. DESIGN: A prism-adaptation design was
      implemented, consisting of pre-exposure, prism exposure, and post-exposure
      phases. Half of the participants were instructed about the function of the prism
      glasses, while the other half were not. MEASURES: For each trial, the distance
      between the target and the shuffled disk was determined. Explicit learning was
      indicated by the rate of adaptation during the prism exposure phase, whereas
      implicit learning was indicated by the magnitude of the negative after-effect at
      the start of the post-exposure phase. Results No significant effects were
      revealed between typically developing participants and participants with
      unilateral cerebral palsy. Comparison of participants with left and right
      unilateral cerebral palsy demonstrated that participants with right unilateral
      cerebral palsy had a significantly lower rate of adaptation than participants
      with left unilateral cerebral palsy, but only when no instructions were provided.
      The magnitude of the negative after-effects did not differ significantly between
      participants with right and left unilateral cerebral palsy. CONCLUSIONS: The
      capacity for explicit motor learning is reduced among individuals with right
      unilateral cerebral palsy when accumulation of declarative knowledge is unguided
      (i.e., discovery learning). In contrast, the capacity for implicit learning
      appears to remain intact among individuals with left as well as right unilateral
      cerebral palsy. Implications for rehabilitation Implicit motor learning
      interventions are recommended for individuals with cerebral palsy, particularly
      for individuals with right unilateral cerebral palsy Explicit motor learning
      interventions for individual with cerebral palsy - if used - best consist of
      singular verbal instruction.

PMID- 28756682
TI  - Vitamin D Status and Kidney Function Decline in HIV-Infected Men: A Longitudinal
      Study in the Multicenter AIDS Cohort Study.
AB  - Vitamin D may play an important role in a range of disease processes. In the
      general population, lower vitamin D levels have been associated with kidney
      dysfunction. HIV-infected populations have a higher risk of chronic kidney
      disease. Few studies have examined the link between lower vitamin D levels and
      kidney function decline among HIV-infected persons. We investigated the
      associations of serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D
      [1,25(OH)2D] with kidney function decline in a cohort of HIV-infected white and
      black men under highly active antiretroviral therapy treatment in the vitamin D
      ancillary study of the Multicenter AIDS Cohort Study. The associations of 25(OH)D
      and 1,25(OH)2D with annual change in estimated glomerular filtration rate (eGFR)
      were evaluated using linear mixed effects models. This study included 187 whites
      and 86 blacks with vitamin D measures and eGFR >=60 ml/min/1.73 m2 at baseline.
      Over a median follow-up of 8.0 years, lower 25(OH)D levels were significantly
      associated with faster eGFR decline in whites (adjusted annual change in eGFR,
      tertile 1: -2.06 ml/min/1.73 m2 vs. tertile 3: -1.23 ml/min/1.73 m2, p trend
      .03), while no significant association was detected in blacks. Lower 1,25(OH)2D
      was associated with faster kidney function decline in both whites and blacks,
      although the estimates were not statistically significant. In conclusion, lower
      25(OH)D levels were significantly associated with faster eGFR decline in a cohort
      of HIV-infected white men, but not in those with black ancestry. Further research
      is warranted to investigate the association of 25(OH)D and 1,25(OH)2D with kidney
      function decline in larger and ethnically diverse populations.

PMID- 28756683
TI  - Factors influencing clinical consistency and variability in voice prosthesis
      management.
AB  - PURPOSE: Anecdotally it is recognised that management of tracheoesophageal speech
      (TES) post-laryngectomy varies between speech language pathology (SLP) services
      and clinicians. This study reviewed patterns of practice for TES management to
      examine patterns of practice and explore factors influencing variability. METHOD:
      A national survey was completed by SLP's from clinical services which manage TES.
      This online survey examined demographic and caseload information, initial voice
      prosthesis (VP) placement and procedures, VP cleaning and care recommendations,
      humidification management, equipment and service provision, and service delivery
      options at each site. RESULT: Lead clinicians from 34 sites (85% response rate)
      responded. Most clinical practice regarding initial VP insertion and management,
      as well as the timing and delivery of voice rehabilitation was highly consistent.
      Patient use of antifungal medications, TES and associated equipment provision,
      humidification management immediately post-surgery and some aspects of initial VP
      insertion were variable between services. The nature of the clinical setting,
      equipment funding and level of research evidence influenced variability in
      practice. CONCLUSION: Variability exists in a number of aspects of practice
      across Australian services offering TES management. Sources of variability need
      to be addressed nationally to ensure there is consistent, quality care available
      for all patients.

PMID- 28756684
TI  - Limitations of traditional health technology assessment methods and implications
      for the evaluation of novel therapies.

PMID- 28756685
TI  - Computer-aided drug design: time to play with novel chemical matter.

PMID- 28756686
TI  - Beyond diagnosis: the Core Sets for persons with schizophrenia based on the World
      Health Organization's International Classification of Functioning, Disability,
      and Health.
AB  - PURPOSE: Based on the International Classification of Functioning, Disability and
      Health (ICF), this paper presents the results of the process to develop the
      Comprehensive and Brief Core Sets for schizophrenia that allow to comprehensively
      describe functioning in persons with schizophrenia. METHODS: Twenty health
      professionals from diverse backgrounds participated in a formal and iterative
      decision-making process during an international consensus conference to develop
      these Core Sets. The conference was carried out based on evidence gathered from
      four preparatory studies (systematic literature review, qualitative study, expert
      survey, and empirical study). The first step of this decision-making and
      consensus process comprised of discussions and voting in working groups and
      plenary sessions to develop the comprehensive version. The categories of the
      Comprehensive ICF Core Set for schizophrenia served as the basis for the second
      step -a ranking and cutoff procedure to decide on the brief version. RESULTS: Of
      the 184 candidate categories identified in the preparatory studies, 97 categories
      were included in the Comprehensive Core Set for schizophrenia. A total of 25
      categories were selected to constitute the Brief Core Set. CONCLUSIONS: The
      formal decision-making and consensus process integrating evidence from four
      preparatory studies and expert opinion led to the first version of the Core Sets
      for schizophrenia. Comprehensive and Brief Core Sets for schizophrenia may
      provide a common language among different health professionals and researchers,
      and a basic international standard of what to measure, report, and assess the
      functioning of persons with schizophrenia. Implications for rehabilitation
      Schizophrenia is a chronic mental disorder that has a tremendous impact on
      functioning and daily life of persons living with the disorder. The International
      Classification of Functioning, Disability and Health (ICF) offers an
      internationally recognized standard for describing the functioning status of
      these individuals. The Core Sets for schizophrenia have potential use in
      supporting rehabilitation practice such as for planning mental health services
      and other interventions or defining rehabilitation goals, and documenting patient
      care. The Core Sets for schizophrenia may also be used to promote
      interdisciplinary coordination and facilitate communication between members of a
      multidisciplinary rehabilitation team. Rehabilitation research is another
      potential area of application of the Core Sets for schizophrenia. This is
      valuable, since rehabilitation research provides crucial evidence for optimizing
      rehabilitation practice.

PMID- 28756687
TI  - The impact of particle preparation methods and polymorphic stability of lipid
      excipients on protein distribution in microparticles.
AB  - OBJECTIVE: The present study aimed at elucidating the influence of polymorphic
      stability of lipid excipients on the physicochemical characters of different
      solid lipid microparticles (SLM), with the focus on the alteration of protein
      distribution in SLM. METHODS: Labeled lysozyme was incorporated into SLM prepared
      with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS),
      and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water
      (s/o/w) method. The distribution of lysozyme in SLM and the release of the
      protein from SLM were evaluated by confocal laser scanning microscopy. The
      storage stability of SLM was characterized by HPLC, differential scanning
      calorimetry, X-ray powder diffraction, and scanning electron microscopy. RESULTS:
      Lysozyme was displayed as small scattered domains inside GDS and GMS SLM, whereas
      it was incorporated in the core of TG14 SLM formulated by the w/o/w method or
      evenly distributed in TG14 SLM prepared by the s/o/w method. Stability study at
      37  degrees C revealed that only TG14 SLM made by the w/o/w method was able to
      maintain the lysozyme amount both on the particle surface and released from the
      SLM. Elevated storage temperature induced polymorphic transition of lipids in GDS
      and GMS SLM, which was, however, not remarkable for the TG14 SLM. CONCLUSIONS:
      Lipid excipients and particle preparation methods were found to differently
      affect the lysozyme distribution in SLM, owning to varied storage stabilities of
      the lipids. The present study provides updated knowledge for rational development
      of lipid-based formulations for oral delivery of peptide or protein drugs.

PMID- 28756688
TI  - Message banking: Perceptions of persons with motor neuron disease, significant
      others and clinicians.
AB  - PURPOSE: Message banking is an intervention strategy that has the potential to
      facilitate effective communication for people with motor neuron disease when
      their condition deteriorates to the extent that they cannot communicate using
      natural speech. The aim of the current study was to determine and compare the
      perceptions on message banking of three stakeholder groups, namely, persons with
      motor neuron disease, their significant others and speech-language pathologists.
      METHOD: A comparative group survey design was used. Participants listened to a
      short presentation about message banking, after which they individually completed
      a questionnaire. RESULT: Although most participants reported that they had never
      heard of message banking, all were interested in it. The survey results revealed
      statistically significant differences between the various groups of stakeholders
      regarding the relevance of message banking and types of messages to bank.
      CONCLUSION: The study concluded that there is limited awareness about message
      banking amongst all participant groups.

PMID- 28756689
TI  - Recreational use of carfentanil - a case report with laboratory confirmation.

PMID- 28756691
TI  - Intervention for children with word-finding difficulties: a parallel group
      randomised control trial.
AB  - PURPOSE: The study investigated the outcome of a word-web intervention for
      children diagnosed with word-finding difficulties (WFDs). METHOD: Twenty children
      age 6-8 years with WFDs confirmed by a discrepancy between comprehension and
      production on the Test of Word Finding-2, were randomly assigned to intervention
      (n = 11) and waiting control (n = 9) groups. The intervention group had six
      sessions of intervention which used word-webs and targeted children's meta
      cognitive awareness and word-retrieval. RESULT: On the treated experimental set
      (n = 25 items) the intervention group gained on average four times as many items
      as the waiting control group (d = 2.30). There were also gains on personally
      chosen items for the intervention group. There was little change on untreated
      items for either group. CONCLUSION: The study is the first randomised control
      trial to demonstrate an effect of word-finding therapy with children with
      language difficulties in mainstream school. The improvement in word-finding for
      treated items was obtained following a clinically realistic intervention in terms
      of approach, intensity and duration.

PMID- 28756690
TI  - Continuous measurements of stable isotopes of carbon dioxide and water vapour in
      an urban atmosphere: isotopic variations associated with meteorological
      conditions.
AB  - Isotope ratios of carbon dioxide and water vapour in the near-surface air were
      continuously measured for one month in an urban area of the city of Nagoya in
      central Japan in September 2010 using laser spectroscopic techniques. During the
      passages of a typhoon and a stationary front in the observation period,
      remarkable changes in the isotope ratios of CO2 and water vapour were observed.
      The isotope ratios of both CO2 and water vapour decreased during the typhoon
      passage. The decreases can be attributed to the air coming from an industrial
      area and the rainout effects of the typhoon, respectively. During the passage of
      the stationary front, delta13C-CO2 and delta18O-CO2 increased, while delta2H-H2Ov
      and delta18O-H2Ov decreased. These changes can be attributed to the air coming
      from rural areas and the air surrounding the observational site changing from a
      subtropical air mass to a subpolar air mass during the passage of the stationary
      front. A clear relationship was observed between the isotopic CO2 and water
      vapour and the meteorological phenomena. Therefore, isotopic information of CO2
      and H2Ov could be used as a tracer of meteorological information.

PMID- 28756692
TI  - The safety of available treatments for chronic constipation.
AB  - INTRODUCTION: Chronic constipation is a frequent syndrome which, not only causes
      an appreciable deterioration in quality of life, but also entails a high economic
      cost due, among other things, to its treatment. This is because of the widespread
      use of laxatives, even by subjects who have not sought medical care, as well as
      little patient satisfaction with the treatment. Although this generally involves
      the use of drugs regarded as safe, there is no clear evidence about their short-
      and long-term effects, something that complicates appropriate prescription and
      follow-up by health professionals and hinders therapeutic compliance. OBJECTIVE:
      To review the adverse effects which have been associated with laxatives based on
      scientific evidence, and ascertain the safety profile of the treatments used for
      constipation. Expert opinion: While all the drugs currently available for
      treatment of constipation are generally safe when used at established doses under
      medical supervision, more rigorous data on their long-term safety are nonetheless
      required, in view of the fact that constipation is a chronic condition. Their
      long-term use should be monitored by health professionals to optimize treatment
      on an individualized basis, with the aim of enhancing efficacy and minimizing
      adverse effects.

PMID- 28756693
TI  - Improved hepatoprotective activity of silymarin via encapsulation in the novel
      vesicular nanosystem bilosomes.
AB  - The main objective of the present work was to formulate, characterize, and
      evaluate silymarin (SM)-loaded bilosomes, compared to conventional liposomes,
      aiming at increasing the hepatoprotective activity of the drug. SM-loaded
      bilosomes were prepared by thin film hydration technique employing soybean
      phosphatidyl choline (SPC) and different bile salts. After being subjected to
      different methods of characterization, SM-loaded bilosomes were investigated for
      their hepatoprotective activity, in CCl4 hepatointoxicated rat model. The
      developed SM dispersions exhibited an entrapment efficiency ranging from 21.80 +/
      2.01 to 84.54 +/- 2.51% and a particle size diameter in the nanometric
      dimensions (413 +/- 96.9 to 686.9 +/- 62.38 nm), with a negative zeta potential
      values (<-45 mV). In vitro release study revealed a lower cumulative amount of
      drug released from the developed formulae, compared to free drug. Ex vivo
      intestinal uptake study, performed using confocal laser scanning calorimetry,
      revealed the superiority of bilosomal uptake compared to that of liposomes. In
      vivo studies revealed an enhanced hepatoprotective effect of SM-loaded
      bilosomes/liposomes compared to free drug. These results were in good correlation
      with histopathological examination. These findings support the potential use of
      bilosomes for improving the hepatoprotective activity of SM via oral
      administration.

PMID- 28756694
TI  - Factors influencing medical staff's intentions to implement family-witnessed
      cardiopulmonary resuscitation: A cross-sectional, multihospital survey.
AB  - BACKGROUND: In Taiwan, the current status of family-witnessed resuscitation (FWR)
      and the factors associated with behavioural intentions to implement FWR have not
      been systematically examined using representative medical staff. AIM: We explored
      predictive factors for behavioural intentions to implement FWR among medical
      staff using constructs from the theory of planned behaviour. METHODS: A survey of
      1605 medical staff from five hospitals in southern Taiwan was conducted. Data
      were collected using a researcher-made questionnaire containing theory of planned
      behaviour constructs and demographic items. The dependent variable was intention
      to implement FWR, and the independent variables were three theory of planned
      behaviour constructs (attitudes, subjective norms, and perceived behavioural
      control) and the demographic characteristics. A generalized estimating equation
      was used to identify factors associated with the behavioural intentions. RESULTS:
      In total, 1122 valid questionnaires revealed that only 3.7% of participants
      advocated FWR policies. The construct scores for intention to implement FWR were
      2.96 (on a five-point Likert scale), and the theory of planned behaviour
      constructs that significantly predicted intention to implement FWR were positive
      attitudes and subjective norms ( p<0.001). Classification of hospitals ( p=0.018)
      and restrictive provisions for FWR ( p=0.004) were additional significant
      predictors of intention to implement FWR. Moreover, medical staff employed at
      regional hospitals demonstrated higher intentions, positive attitudes and
      subjective norms than did those employed at the medical centre. CONCLUSION:
      According to the findings of this study, it may be desirable for administrators
      to prioritize the implementation of the FWR policy in regional hospitals. We
      recommend affording the factors of positive attitudes and subjective norms high
      priority to improve the medical staff's behavioural intentions of FWR practice.

PMID- 28756695
TI  - Cardiometabolic risks, lifestyle health behaviors and heart disease in Filipino
      Americans.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death among all racial
      and ethnic populations in the USA. Cardiovascular risks and cardioprotective
      factors have been disparately estimated among Asian American subpopulations.
      AIMS: The study's purpose was to describe the cardiometabolic risks and lifestyle
      health behaviors associated with cardiovascular disease, considering age and
      gender, in Filipinos, the second largest Asian American population. METHODS:
      Secondary analysis was conducted of behavioral (smoking, walking, body mass index
      and soda, fast food and fruit/vegetable consumption), cardiometabolic
      (hypertension and diabetes) and heart disease variables in the 2011-2012
      California Health Interview Survey. The metropolitan sample of Filipino American
      adults included 57.3% women and had a mean age of 47.9 +/- 18.3 years ( n = 555).
      RESULTS: Among the sample, 7.4% had heart disease, 38.9% had hypertension, 16.6%
      had diabetes, 12.4% smoked cigarettes, 83.2% were insufficiently active, 54.2%
      were overweight/obese, 21.8% routinely ate fast food, 13.2% routinely drank soda
      and 90.3% did not meet the fruit/vegetable consumption recommendation. Age
      (unadjusted odds ratio [OR] = 1.0, p < 0.0001), hypertension (unadjusted OR =
      4.8, p < 0.0001) and diabetes (unadjusted OR = 3.3, p = 0.001) were associated
      with heart disease. Hypertension was the single greatest heart disease risk,
      controlling for diabetes, age and gender (adjusted OR = 3.1, p = 0.006).
      CONCLUSIONS: Primary and secondary prevention and treatment of hypertension
      should be paramount, along with promotion of glucose control, regular moderate
      intensity physical activity, weight management and increased fruit and vegetable
      consumption in the Filipino American population. A multidisciplinary, chronic
      care model that is population-specific, emphasizes integrated, comprehensive care
      and provides linkages between primary healthcare and community resources is
      recommended for practice.

PMID- 28756696
TI  - Identification of factors associated with self-care behaviors using the COM-B
      model in patients with chronic heart failure.
AB  - BACKGROUND: Self-care can improve heart failure outcomes. Self-care confidence is
      associated with self-care behaviors and may serve as a mediator between potential
      influencing factors (e.g. functional capacity, knowledge, and health literacy)
      and self-care behaviors. However, evidence is limited on these relationships. The
      COM-B model (consisting of capability, opportunity, and motivation) may be an
      appropriate framework to understand the above relationships. AIM: The purpose of
      this study was to explore factors associated with self-care behaviors and to
      examine the mediating role of self-care confidence. METHODS: Three hundred and
      twenty-one patients (mean age 64 years, 51% male) with chronic heart failure
      completed measures of functional capacity, knowledge, health literacy, social
      support, socioeconomic status, self-care, and sociodemographic and clinical
      characteristics. Structural equation modeling was used to analyze the data.
      RESULTS: The scores for self-care maintenance and management were 48.4+/-15.9 and
      54.3+/-19.3, respectively. The revised model showed good fit (root mean square
      error of approximation=0.029; comparative fit index=0.989). Functional capacity
      and knowledge were directly associated with self-care management, and health
      literacy and social support were directly related to self-care maintenance.
      Moreover, self-care confidence mediated the relationships between knowledge,
      health literacy, social support and self-care behaviors. CONCLUSIONS: Chinese
      patients with chronic heart failure have poor self-care behaviors. Factors
      associated with self-care behaviors are confidence, functional capacity,
      knowledge, health literacy and social support. Self-care confidence appears to be
      a mediator between knowledge, health literacy, social support and self-care
      behaviors. Targeted interventions are required to optimize self-care behaviors in
      patients with chronic heart failure.

PMID- 28756697
TI  - Early detection of oral health status and cardiometabolic risk factors among
      reproductive-aged women in rural areas: A cross-sectional study.
AB  - BACKGROUND: Oral health status is associated with many chronic ailments,
      including diseases of the cardiovascular system, diabetes, as well as pregnancy
      complications, such as low birth weight, preterm delivery, preeclampsia, and
      early pregnancy loss. The health status of reproductive-aged women is important,
      not only for the women themselves, but also for the health of fetus. OBJECTIVES:
      The purpose of this study was to explore cardiometabolic risk factors, oral
      health status, and associated factors among reproductive-aged women. METHODS: The
      current study is a preliminary report from a nurse-led longitudinal study,
      examining a health promotion program for women in a rural region of Taiwan.
      Participants consisted of a community-based, cross-sectional sample, involving
      2547 women aged 20-49 years. RESULTS: A high percentage of participants were
      found to have cardiometabolic risk factors. More than one-quarter had ?24
      remaining teeth. Many participants reported that they did not regularly attend
      dental checkups and tooth scaling, did not brush at least twice a day after
      meals, did not have a healthy diet, and did not exercise regularly. The results
      also indicated that women with <20 remaining teeth tended to be older, engaged in
      substance use, and displayed increased cardiometabolic risk factors. CONCLUSIONS:
      The findings indicate that reproductive-aged women show a high prevalence of
      tooth loss, cardiometabolic risk factors, and unhealthy habits. Nurses in the
      primary health sectors could reduce the consequences of these risk factors and
      improve oral health through the early detection and initiation of health
      promoting programs that reduce risky behavior associated with cardiometabolic
      diseases.

PMID- 28756698
TI  - Patient outcomes after transcatheter and surgical pulmonary valve replacement for
      pulmonary regurgitation in patients with repaired tetralogy of Fallot: A quasi
      meta-analysis.
AB  - BACKGROUND: Individuals with repaired tetralogy of Fallot develop pulmonary
      regurgitation that may cause symptoms (dyspnea, chest pain, palpitations,
      fatigue, presyncope, and syncope), impair functional capacity, and may affect
      health-related quality of life. Surgical pulmonary valve replacement is the gold
      standard of treatment although transcatheter pulmonary valve replacement is
      becoming more common. Patients want to know whether less invasive options are as
      good. AIMS: This analysis aimed to examine the differences in surgical versus
      transcatheter pulmonary valve replacement effects in terms of
      physiological/biological variables, symptoms, functional status and health
      related quality of life. METHODS: This quasi-meta-analysis included 85 surgical
      and 47 transcatheter pulmonary valve replacement studies published between 1995
      2016. RESULTS: In terms of physiological/biological variables, both surgical and
      transcatheter pulmonary valve replacement improved pulmonary regurgitation and
      systolic and diastolic right ventricular volume indices but not heart function.
      In the left heart, only surgical pulmonary valve replacement improved heart
      function. Only transcatheter pulmonary valve replacement improved left
      ventricular end-diastolic indices and neither improved endsystolic indices. Only
      surgery has been demonstrated to decrease QRS duration but there is little
      evidence of arrhythmia reduction. Symptom change is poorly documented. Functional
      class improves but exercise capacity generally does not. Some aspects of health
      related quality of life improve with surgery and in one small transcatheter
      pulmonary valve replacement study. CONCLUSION: Transcatheter and surgical
      pulmonary valve replacement compare favorably for heart remodeling. Exercise
      capacity does not change with either technique. Health-related quality of life
      improves after surgical pulmonary valve replacement. There are numerous gaps in
      documentation of changes in arrhythmias and symptoms.

PMID- 28756701
TI  - Looking for Common Fingerprints in Leonardo's Pupils Using Nondestructive Pigment
      Characterization.
AB  - Non-invasive, portable analytical techniques are becoming increasingly widespread
      for the study and conservation in the field of cultural heritage, proving that a
      good data handling, supported by a deep knowledge of the techniques themselves,
      and the right synergy can give surprisingly substantial results when using
      portable but reliable instrumentation. In this work, pigment characterization was
      carried out on 21 Leonardesque paintings applying in situ X-ray fluorescence
      (XRF) and fiber optic reflection spectroscopy (FORS) analyses. In-depth data
      evaluation allowed to get information on the color palette and the painting
      technique of the different artists and workshops . Particular attention was paid
      to green pigments (for which a deeper study of possible pigments and alterations
      was performed with FORS analyses), flesh tones (for which a comparison with
      available data from cross-sections was made), and ground preparation.

PMID- 28756700
TI  - Determination of Spatially Resolved Tablet Density and Hardness Using Near
      Infrared Chemical Imaging (NIR-CI).
AB  - Near-infrared chemical imaging (NIR-CI) combines spectroscopy with digital
      imaging, enabling spatially resolved analysis and characterization of
      pharmaceutical samples. Hardness and relative density are critical quality
      attributes (CQA) that affect tablet performance. Intra-sample density or hardness
      variability can reveal deficiencies in formulation design or the tableting
      process. This study was designed to develop NIR-CI methods to predict spatially
      resolved tablet density and hardness. The method was implemented using a two-step
      procedure. First, NIR-CI was used to develop a relative density/solid fraction
      (SF) prediction method for pure microcrystalline cellulose (MCC) compacts only. A
      partial least squares (PLS) model for predicting SF was generated by regressing
      the spectra of certain representative pixels selected from each image against the
      compact SF. Pixel selection was accomplished with a threshold based on the
      Euclidean distance from the median tablet spectrum. Second, micro-indentation was
      performed on the calibration compacts to obtain hardness values. A univariate
      model was developed by relating the empirical hardness values to the NIR-CI
      predicted SF at the micro-indented pixel locations: this model generated
      spatially resolved hardness predictions for the entire tablet surface.

PMID- 28756702
TI  - Measurements of Strontium Levels in Human Bone In Vivo Using Portable X-ray
      Fluorescence (XRF).
AB  - Measurement of bone strontium (Sr) is vital to determining the effectiveness of
      Sr supplementation, which is commonly used for the treatment of osteoporosis.
      Previous technology uses radioisotope sources and bulky equipment to measure bone
      Sr. This study demonstrates the effectiveness of portable X-ray fluorescence
      (XRF) for bone Sr measurement and validates it using data from a population of
      238 children. We identified correlations between bone Sr and age in our
      participants.

PMID- 28756703
TI  - Hydrodemetallation and Hydrodesulfurization Spent Catalysts Elemental Analysis:
      Comparison of Wavelength Dispersive X-ray Fluorescence and Atomic Emission
      Spectrometries.
AB  - Petroleum industries continuously consume catalysts on very large scales. The
      recycling of spent catalysts is thus of major economic and environmental
      importance and its first step consists of the characterization of the valuable
      metal content. Wavelength dispersive X-ray fluorescence (WDXRF) analysis is
      compared with inductively coupled plasma atomic emission spectrometry (ICP-AES)
      for the analysis of five samples of spent hydrodesulphurization (HDS) and
      hydrodemetallization (HDM) catalysts. The elements are considered for their
      economic interest (Co, Ni, Mo, and V) or for the problems that can arise when
      they are present in the sample in significant quantities (Al, As, P, Fe). First,
      the systematic comparison of the analysis of known synthetic samples was
      performed. The originality here is that the samples were first beaded with
      lithium tetraborate (Li2B4O7) for WDXRF analysis and then dissolved in hot HCl 6M
      for ICP-AES measurements. With this processing, we were able to clearly identify
      the origin of analytical problems when they arose. Second, the semi-quantitative
      protocol of WDXRF is compared with the quantitative procedure. Finally, the
      analysis of the spent catalysts is presented and the information gained by the
      systematic comparison of ICP-AES and WDXRF is shared. The interest of the
      simultaneous determination by the two techniques when such complicated
      heterogeneous matrices are involved is clearly demonstrated.

PMID- 28756704
TI  - Implementation of Resonance Tracking for Assuring Reliability in Resonance
      Enhanced Photothermal Infrared Spectroscopy and Imaging.
AB  - Photothermal-induced resonance (PTIR) is a method for optical spectroscopy that
      allows for infrared (IR) chemical imaging at spatial resolution below the limit
      of diffraction. By using the mechanical resonance of the cantilever for
      amplification the technique has been shown to allow sensitivity down to single
      monolayers. In this work, we discuss the challenges that must be overcome for
      performing stable resonant PTIR measurements and how imprecise experimental
      procedures can lead to irreproducible or even erroneous results. We also present
      a controller design that continuously readjusts the excitation frequency of a
      PTIR setup back to the resonance frequency in order to allow for accurate
      resonance-enhanced PTIR measurements. This controller can be used together with a
      broad range of atomic force microscopes. Schematics and program code for the
      controller are made freely available.

PMID- 28756705
TI  - Raman Microspectroscopic Mapping with Multivariate Curve Resolution-Alternating
      Least Squares (MCR-ALS) Applied to the High-Pressure Polymorph of Titanium
      Dioxide, TiO2-II.
AB  - The high-pressure, alpha-PbO2-structured polymorph of titanium dioxide (TiO2-II)
      was recently identified in micrometer-sized grains recovered from four Neoarchean
      spherule layers deposited between ~2.65 and ~2.54 billion years ago. Several
      lines of evidence support the interpretation that these layers represent distal
      impact ejecta layers. The presence of shock-induced TiO2-II provides physical
      evidence to further support an impact origin for these spherule layers. Detailed
      characterization of the distribution of TiO2-II in these grains may be useful for
      correlating the layers, estimating the paleodistances of the layers from their
      source craters, and providing insight into the formation of the TiO2-II. Here we
      report the investigation of TiO2-II-bearing grains from these four spherule
      layers using multivariate curve resolution-alternating least squares (MCR-ALS)
      applied to Raman microspectroscopic mapping. Raman spectra provide evidence of
      grains consisting primarily of rutile (TiO2) and TiO2-II, as shown by Raman bands
      at 174 cm-1 (TiO2-II), 426 cm-1 (TiO2-II), 443 cm-1 (rutile), and 610 cm-1
      (rutile). Principal component analysis (PCA) yielded a predominantly three-phase
      system comprised of rutile, TiO2-II, and substrate-adhesive epoxy. Scanning
      electron microscopy (SEM) suggests heterogeneous grains containing polydispersed
      micrometer- and submicrometer-sized particles. Multivariate curve resolution
      alternating least squares applied to the Raman microspectroscopic mapping yielded
      up to five distinct chemical components: three phases of TiO2 (rutile, TiO2-II,
      and anatase), quartz (SiO2), and substrate-adhesive epoxy. Spectral profiles and
      spatially resolved chemical maps of the pure chemical components were generated
      using MCR-ALS applied to the Raman microspectroscopic maps. The spatial
      resolution of the Raman microspectroscopic maps was enhanced in comparable, cost
      effective analysis times by limiting spectral resolution and optimizing spectral
      acquisition parameters. Using the resolved spectra of TiO2-II generated from MCR
      ALS analysis, a Raman spectrum for pure TiO2-II was estimated to further
      facilitate its identification.

PMID- 28756706
TI  - Determination of Depth in Transmission Raman Spectroscopy in Turbid Media Using a
      Beam Enhancing Element.
AB  - This study demonstrates experimentally a method to enable prediction of depth of
      a chemical species buried in a turbid medium by using transmission Raman
      spectroscopy alone. The method allows the prediction of the depth of a single,
      chemically distinct layer within a turbid matrix by performing two measurements,
      with and without a beam enhancing element, or "photon diode." The samples
      employed consisted of two different polymers, of total thickness 3.6 mm, whose
      optical properties are loosely relevant to pharmaceutical applications. A polymer
      layer of low-density polyethylene (LDPE) was placed at different positions within
      multiple layers of the polytetrafluoroethylene (PTFE) matrix and Raman spectra
      were recorded in each case. Both univariate and multivariate analyses were
      utilized to determine whether the depth of the LDPE layer could be predicted
      using the obtained data. The best-achieved RMSE of prediction was 4.2% of the
      total sample size (i.e., +/- 0.15 mm) with the multivariate approach.

PMID- 28756708
TI  - Biomarkers of necrotizing enterocolitis: a review of literature.
AB  - Necrotizing enterocolitis (NEC) is among the most serious gastrointestinal
      emergency in very low birth weight (VLBW), extremely low birth weight (ELBW) and
      extremely low gestational age neonates (ELGAN), affecting 7-14% of these
      neonates. Despite extensive research, the underlying aetiology of NEC still
      remains blurred. Due to high mortality, morbidity and its delayed presentation,
      early detection of NEC is considered to be lifesaving. A number of biomarkers
      have been studied for early detection and prediction of severity of NEC but till
      date, no ideal marker has been discovered. Molecular techniques like proteomic
      and metabolomic have recently emerged in the field for the development of
      biomarkers for early detection and understanding the pathophysiology of NEC. We
      did literature search for identifying all biomarkers that have been used for the
      detection of NEC and, in this review article, we discuss these biomarkers along
      with the available current evidence.

PMID- 28756707
TI  - Emerging vascular endothelial growth factor antagonists to treat neovascular age
      related macular degeneration.
AB  - INTRODUCTION: Evolving anti-vascular endothelial growth factor (VEGF) treatments
      for neovascular age-related macular degeneration (nAMD) include long acting
      agents, combination strategies involving new pathways, topical agents, sustained
      release, and genetic therapy strategies. Areas covered: Brolucizumab and abicipar
      pegol have smaller molecular size, facilitating higher concentrations and
      potentially longer duration than current anti-VEGF agents. Agents being combined
      with anti-VEGFs include OPT-302 (to inhibit VEGF-C and VEGF-D); pegpleranib and
      rinucumab (to inhibit platelet derived growth factor, PDGF - but both failed to
      show consistently improved visual outcomes compared to anti-VEGF monotherapy);
      and RG7716, ARP-1536 and nesvacumab (to activate the Tie-2 tyrosine kinase
      receptor, which reduces permeability). X-82 is an oral anti-VEGF and anti-PDGF
      being tested in phase 2 studies. Topical anti-VEGF +/- anti-PDGF drugs under
      study include pazopanib, PAN-90806, squalamine lactate, regorafinib, and LHA510.
      Sustained-release anti-VEGF delivery treatments, such as the ranibizumab Port
      Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305 aim to
      reduce the burden of frequent injections. Gene therapies with new viral vectors
      hold the potential to induce sustained expression of anti-angiogenic proteins via
      the retina's cellular apparatus, and include AVA-101/201, ADVM-202/302, AAV2
      sFLT01, RGX314, and Retinostat. Expert opinion: There are many emerging anti-VEGF
      treatments that aim to improve visual outcomes and reduce the treatment burden of
      nAMD.

PMID- 28756709
TI  - Emerging anabolic agents in the treatment of osteoporosis.
AB  - INTRODUCTION: Osteoporosis is a common skeletal disease with serious consequences
      due to osteoporotic fractures and high costs to society for post-fracture care.
      Most patients at high risk for fracture are not receiving care to reduce fracture
      risk. The osteoporosis treatment gap has reached crisis proportions. Strategies
      to reduce the treatment gap include systematic methods for identifying and
      treating high risk patients, better education of patients and healthcare
      providers, better use of currently available drugs, and development of new drugs
      to treat osteoporosis. Areas covered: Two osteoanabolic agents with novel
      mechanisms of action have recently completed phase 3 clinical trials. The
      efficacy and safety findings of these studies are reviewed. Abaloparatide, a
      synthetic analog of parathyroid hormone-related protein, has received regulatory
      approval for the treatment of postmenopausal women with osteoporosis at high risk
      for fracture. Romosozumab, a humanized monoclonal antibody to sclerostin, an
      endogenous inhibitor of bone formation, is under regulatory review. Expert
      opinion: Osteoanabolic therapy for osteoporosis can restore, at least in part,
      the degradation of bone microarchitecture that is a hallmark of this disease. The
      emergence of new osteoanabolic compounds expands the treatment options for
      patients at high risk for fracture.

PMID- 28756710
TI  - Steroid therapy and renal dysfunction are independently associated with serum
      levels of matrix metalloproteinase-3 in patients with rheumatoid arthritis.
AB  - OBJECTIVE: This study aimed to evaluate whether the level of serum matrix
      metalloproteinase-3 (MMP-3), a marker of synovium inflammation, is affected by
      clinical characteristics of patients in rheumatoid arthritis (RA) patients.
      METHODS: We analyzed data from 1087 female patients with RA. Pearson's
      correlation coefficients were calculated to explore associations between
      variables. Stepwise multiple linear regression analysis was performed to evaluate
      patient background variables that could potentially affect serum MMP-3 levels.
      RESULTS: Serum MMP-3 was moderately correlated with C-reactive protein (CRP) (r:
      0.478). Factors that independently influenced serum MMP-3 levels were CRP (beta:
      0.450), prednisolone (PSL) use (beta: 0.100), estimated glomerular filtration
      rate (eGFR) (beta: -0.085), swollen joint count assessed on 28 joints (beta:
      0.072), and body mass index (beta: -0.061) in female patients with RA. In RA
      patients with PSL use, factors that independently influenced serum MMP-3 levels
      were CRP (beta: 0.480), eGFR (beta: -0.175), and PSL dose (beta: 0.171).
      CONCLUSIONS: Our findings suggest that steroid therapy and renal dysfunction
      affect serum MMP-3 levels in patients with RA.

PMID- 28756711
TI  - The potential of obscurin as a therapeutic target in muscle disorders.
AB  - INTRODUCTION: Obscurin, a giant protein of striated muscles, is emerging as an
      important player in a wide range of processes including myofibril assembly and
      maintenance, muscle protein degradation and intracellular signaling. Accordingly,
      obscurin participates to the mechanisms by which muscles adapt to physiological
      requirements or to pathological cues associated with cardiac and skeletal muscle
      diseases. Areas covered: The structure of the different obscurin isoforms
      identified so far, their tissue distribution and the most recent findings on
      obscurin in invertebrates and mammals will be reviewed. We will provide a
      synopsis of known molecular interactions between obscurin and other proteins and
      the biological relevance of these interactions for striated muscle function. The
      involvement of obscurin in protein degradation mechanisms and intracellular
      signaling will be also discussed along with initial evidence of a role of
      obscurin in the pathophysiology of human diseases. Expert opinion: Although still
      much remains to be discovered about the role of obscurin either as a structural
      component of the sarcomere or as a mediator of signaling pathways within muscle
      cells, it can be envisioned that this protein represents an interesting novel
      pharmacological target for the prevention and treatment of cardiac and skeletal
      muscle diseases.

PMID- 28756712
TI  - Correction to: Clinical significance of primary symptoms in women with placental
      abruption.

PMID- 28756713
TI  - Coumarin derivatives: an updated patent review (2015-2016).
AB  - INTRODUCTION: Coumarins belong to the benzopyrone family. They are naturally
      plant-derived or synthetically obtained substances, presenting a wide variety of
      biological activities, offering an extented therapeutic profile. Their structural
      characteristics correlated to physicochemical properties define their pleiotropic
      biological responses. AREAS COVERED IN THIS REVIEW: Recent patent publications
      (2015-2016), describing coumarins and their derivatives are analyzed. Synthesis,
      biological evaluations in vitro /in vivo e.g. antiviral, anticancer, cytotoxic,
      antioxidant, anti-inflammmatory protocols are included. Furthermore, several
      pharmaceutical applications and pharmaceutical compositions are also described.
      Expert opinion: Several synthetic coumarins, hybrids and derivatives (azoles,
      sulfonyl, furazan, pyrazole etc) have been found to possess promising anticancer,
      antitumor anti-proliferative activities. Their clinical evaluation will be
      critical to assess therapeutic utility. The compounds for which the mechanism of
      action is well defined can serve as lead compounds for the design of new more
      potent molecules.

PMID- 28756714
TI  - Deciphering the MHC-associated peptidome: a review of naturally processed ligand
      data.
AB  - INTRODUCTION: The availability of big data sets ('OMICS') has greatly impacted
      fundamental and translational science. High-throughput analysis of HLA class I
      and II associated peptidomes by mass spectrometry (MS) has generated large
      datasets, with the last decade witnessing tremendous growth in the breadth and
      number of studies. Areas covered: For this, we first analyzed naturally processed
      peptide (NP) data captured within the IEDB to survey and characterize the current
      state of NP data. We next asked to what extent the NP data overlap with existing
      T cell epitope and MHC binding data. Expert commentary: The current collection of
      NP data represents a large and diverse set of class I/II peptides mostly derived
      from self-antigens. These data overlap only marginally with existing
      immunogenicity and binding data and it is thus difficult to ascertain the
      correspondence between the different assay methodologies. This highlights a need
      for unbiased studies benchmarking in model antigen systems how well MHC binding
      and NP data predicts immunogenicity. Going forward, efforts at generating an
      integrated process for capturing all NP, curating associated metadata and
      accessing NP data from an immunological viewpoint will be important for
      development of novel methods for identifying optimal target antigens and for
      class I and II epitope prediction.

PMID- 28756715
TI  - Development of the rectal dosage form with silver-coated glass beads for local
      action applications in lower sections of the gastrointestinal tract.
AB  - CONTEXT: Recent findings indicating the anti-inflammatory action of silver
      preparations through modulation of the gut microbiota and apoptosis of
      inflammatory cells predestine silver use in inflammatory bowel disease (IBD).
      OBJECTIVE: The aim of our study was to validate the possibility of effective
      silver release from silver-coated glass beads for anti-inflammatory local
      application in the lower sections of the gastrointestinal (GI) tract. MATERIALS
      AND METHODS: Silver-coated glass beads were prepared using magnetron method.
      Release of silver from the silver-coated glass bead surface was carried out in
      BIO-DIS reciprocating cylinder apparatus. Erosion of silver coating and indirect
      estimation of the silver release dynamics was assessed using scanning electron
      microscope. Rectal suppositories containing silver-coated glass beads were
      prepared using five different methods (M1-M5) and X-ray scanned for their
      composition. RESULTS AND DISCUSSION: The XR microanalysis and the chemical
      composition analysis evidenced for a rapid (within 30 min) release of nearly 50%
      of silver from the coating of the glass beads, which remained stable up to 24 h
      of incubation. The most homogeneous distribution of beads in the entire volume of
      the suppository was obtained for formulation M5, where the molten base was poured
      into mold placed in an ice bath, and the beads were added after 10 s.
      CONCLUSIONS: Our study is the first to present the concept of enclosing silver
      coated glass beads in the lipophilic suppository base to attenuate inflammation
      in the lower GI tract and promises efficient treatment with reduced side effects.

PMID- 28756716
TI  - Impact of hepatitis C virus infection on health-related quality of life before
      and after liver transplantation: a multidisciplinary point of view.
AB  - INTRODUCTION: Hepatitis C negatively changes patient quality of life even in the
      absence of advanced liver disease. The specific patterns of quality of life of
      hepatitis C positive patients waiting for transplant or after surgery are not
      widely studied. Areas covered: A significant percentage of infected patients show
      cognitive impairment, fatigue, and/or a 'brain fog', that cannot be explained by
      the liver disease. Depression can be diagnosed in one third of hepatitis C
      positive patients. Conflicting data are available regarding the possible role of
      Model for End-Stage Liver Disease score as predictor of impaired quality of life.
      In the first period after liver transplant, quality of life tends to increase at
      the pre-transplant period but in the medium and long-term period, it declines.
      The recurrence of hepatitis C infection represents a strong predictor of
      morbidity and mortality and can significantly affect the global quality of life
      of patients. Expert commentary: Hepatologists, surgeons and psychologists should
      collaborate to support infected patients in all phases of transplant including
      the long-term period after surgery. Education and information should be
      implemented especially regarding the positive role of new direct antivirals.

PMID- 28756717
TI  - Morphological and genetic divergence between lake and river populations of
      Triplophysa in Ngangtse Co, Tibet.
AB  - Ngangtse Co (4535 m a.s.l., 840 km2) is a typical endorheic lake in Tibet. In
      2015, we investigated the fish resource in this lake and its rivers and collected
      two Triplophysa species, including T. brevicauda and T. stewarti. To understand
      the evolutionary dynamics of Triplophysa in Ngangtse Co, the adaptive and genetic
      divergence between river and lake populations were investigated by analysing
      their morphological characteristics and mitochondrial COI and Cytb sequences.
      Among all of 277 samples, the ratios of the number of T. brevicauda to T.
      stewarti were 27:8, 34:11, 14:24, 37:0, 16:23 and 0:83 in river populations RA,
      RB, RC, RD, lakeside population LSE and lake population L, respectively. For T.
      brevicauda, a small but significant genetic divergence (mean FST = 0.0890) was
      detected between population RD and other three river populations, and significant
      morphological differences of body length/body height and body length/caudal
      peduncle length were observed between population RD and RA, RB, suggesting an
      association between differentiation and geographical distance. For T. stewarti,
      very high levels of genetic differentiation was observed between population L and
      other populations with the FST values ranging from 0.4737 (L-RA) to 0.7074 (L
      RC). In addition, significant differences of most of morphological
      characteristics were observed between the lake (L) and river (RC) populations,
      indicating that lake fish of T. stewarti was a population that showed a long-term
      adaptation to the saltwater lake. These results provide insights on the
      evolutionary dynamics of Triplophysa in Ngangtse Co and help us to understand the
      fish speciation in endorheic lakes on the Qinghai-Tibetan Plateau.

PMID- 28756718
TI  - Pharmacotherapy of glaucoma: new opportunities, old challenges.

PMID- 28756719
TI  - Endograft Infection After Endovascular Abdominal Aortic Aneurysm Repair: A
      Systematic Review and Meta-analysis.
AB  - PURPOSE: To report a meta-analysis of the published evidence on the outcomes of
      aortic endograft infection after endovascular aneurysm repair (EVAR). METHODS: A
      search of electronic information sources (PubMed/MEDLINE, SCOPUS, CENTRAL) and
      bibliographic reference lists identified 12 studies reporting on 362 patients
      (mean age 72 years; 279 men). The methodological quality of the selected studies
      was assessed using the Newcastle-Ottawa scale. Endpoints were 30-day/in-hospital
      mortality and follow-up mortality. Pooled estimates are reported with the 95%
      confidence interval (CI). The review was registered at the International
      Prospective Register of Systematic Reviews in Health and Social Care
      (CRD42016034166). RESULTS: The incidence of graft infection after EVAR was 0.6%
      (95% CI 0.4% to 0.8%). The time from implantation to diagnosis ranged from 1 to
      128 months (mean 25). The majority of patients (293, 81%) underwent surgical
      treatment (95% CI 77% to 83%); 9 (2.5%) patients (95% CI 21% to 43%) received
      conservative treatment. Aortic replacement with a prosthetic graft was performed
      in 58% (95% CI 52% to 62%), whereas cryopreserved allografts and autologous
      grafts were used in 31% (95% CI 28% to 33%) and 11% (95% CI% 8 to 14%),
      respectively. Less than half of the patients (40%) had emergency surgery. The
      pooled estimate of 30-day/in-hospital mortality was 26.6% (95% CI 16.9% to
      39.2%). The pooled 30-day/in-hospital mortality for 9 patients treated
      conservatively was 63.3% (95% CI 30.7% to 87.0%). The pooled overall follow-up
      mortality was 45.7% (95% CI 36.4% to 55.4%) vs 58.6% (95% CI 28.8% to 83.3%) for
      the 9 patients receiving conservative treatment. CONCLUSION: Aortic endograft
      infection is a rare complication after EVAR. Surgical treatment with complete
      explantation of the infected endograft seems to be the optimal management in
      selected patients. Supportive medical treatment without surgical intervention has
      a significant associated mortality.

PMID- 28756720
TI  - Exploration of mtDNA control region sequences in Chinese Tibetan Mastiffs.
AB  - The control region of mitochondrial DNA (mtDNA) was obtained from 40 purebred
      Chinese Tibetan Mastiffs (TMs). Sequence structure and genetic diversity were
      analyzed, and a phylogenetic tree was constructed. The TM mtDNA control region
      was composed of ETAS (extended termination associated sequences), CD (a central
      domain) and CSBs (conserved sequenced blocks) and sequence length showed some
      diversity, which was mainly caused by the number of 10 nucleotide repeat units
      [5'-GTA CAC GT (G/A) C-3'] between CSB I and CSB II, which ranged from 27 to 35
      among individuals. Seventy-five polymorphic sites were identified, which defined
      37 haplotypes; the haplotype diversity was 0.990, and the nucleotide diversity
      was 1.201. Based on the control region sequences, Chinese TMs were divided into
      three categories, which were consistent with the origin and geographical
      classification of TMs. Phylogenetic analysis of 538-bp HVR-I sequences revealed
      that TMs were most closely related to Labrador Retrievers.

PMID- 28756721
TI  - Tissue shrinkage in microwave thermal ablation: comparison of three commercial
      devices.
AB  - PURPOSE: To evaluate, characterise and compare the extent of tissue shrinkage
      induced from three different commercial microwave ablation devices, and to
      elucidate the mechanism behind the distinctive performances obtained. MATERIALS
      AND METHODS: Microwave ablation (N = 152) was conducted with three different
      commercial devices on cubes of ex vivo liver (10-40 +/- 2 mm/side) embedded in
      agar phantoms. 50-60 W was applied for 1-10 min duration. Pre- and post-ablation
      dimensions of the samples, as well as the extent of carbonisation and coagulation
      were measured and correlated. ANOVA was performed to evaluate statistical
      significance. RESULTS: For all devices, logarithmic correlations with time were
      observed for both tissue shrinkage (R2 = 0.84-1.00) and induced carbonisation (R2
      = 0.73-0.99) radially to the antenna axis. Along the longitudinal axis of the
      antenna, for two of the devices shrinkage did not appreciably change with time (p
      > 0.05), yet carbonisation increased linearly (R2 = 0.57-0.94). For the third
      fully internally-cooled device, both carbonisation and shrinkage showed
      logarithmic trends (R2 = 0.85-0.98 and R2 = 0.78-0.94, respectively) based upon
      delayed carbonisation appearing only 5 min into ablation and onward. For all
      devices, non-uniform shrinkage was noted within the coagulated area increasing
      from the boundary of the ablated area (14%) to the limit of carbonisation (39%)
      in a linear fashion (R2 = 0.88) Conclusions: Microwave ablation device
      construction can alter the extent of post-ablation coagulation and tissue
      shrinkage. Given that tissue shrinkage in the coagulated area shows non-uniform
      behaviour, observed differences can be attributed in part to the applicator
      cooling system that alters the ablation temperature profile.

PMID- 28756722
TI  - The role of novel biomarker HE4 in the diagnosis, prognosis and follow-up of
      ovarian cancer: a systematic review.
AB  - INTRODUCTION: Ovarian cancer is the leading cause of death from gynecologic
      cancers, in fact, >80% of cases are diagnosed as advanced-stage disease
      associated with a high mortality rate (<40% of women cured). A systematic review
      was performed to estimate the role of HE4 in the diagnosis, prognosis and follow
      up of ovarian tumors. Areas covered: A comprehensive search of the literature
      from January 1952 to August 2016 was conducted using the terms 'ovarian tumor'
      and 'ovarian cancer' combined with 'HE4' and 'human epididymis protein 4'. The
      search identified a total of 259 citations, of which 141 were potentially
      relevant after initial evaluation. Of these studies, 75 primary studies met the
      inclusion criteria and were analyzed, with a total of 14,773 patients. Expert
      commentary: Serum HE4 dosage is a useful preoperative test for predicting the
      benign or malignant nature of pelvic masses. It seems to have a promising role in
      the prediction of clinical and surgical outcomes. Moreover, HE4 seems to better
      predict recurrence in comparison to CA-125.

PMID- 28756723
TI  - Novel pharmacological treatments for children and adolescents with heterozygous
      familial hypercholesterolemia.

PMID- 28756724
TI  - Medical expulsive therapy in urolithiasis: a mixed treatment comparison network
      meta-analysis of randomized controlled clinical trials.
AB  - BACKGROUND: Medical expulsive therapy (MET) using alpha blockers, calcium channel
      blockers (CCB), phosphodiesterase inhibitors (PDEI) and spasmolytics have been
      shown to be effective in clinical trials on urolithiasis. The present study is a
      network meta-analysis comparing the above mentioned drug classes. RESEARCH DESIGN
      AND METHODS: Electronic databases were searched for randomized controlled trials
      comparing the above mentioned drug classes in patients with urolithiasis using
      appropriate search strategy. Inverse variance heterogeneity model was used for
      the mixed treatment comparisons. Stone expulsion rate (SER) was the primary and
      stone expulsion time (SET) was the main secondary outcome measure. RESULTS: We
      included a total of 114 studies for systematic review and 108 studies for the
      network meta-analysis. Alpha blockers, PDEI, and combined alpha blockers and
      corticosteroids had significantly increased SER and shorter SET than placebo or
      standard of care. Alpha blockers have the highest probability of being the 'best'
      in the pool with regard to SER. This effect persisted in patients with stones >=
      5 mm, children, after shockwave lithotripsy, proximal ureteric stones and distal
      ureteric stones. CONCLUSION: To conclude, we observed a statistically significant
      increase in the expulsion rate and shorter expulsion time with alpha blockers,
      PDEI and combined alpha blockers with corticosteroids. Of these interventions,
      alpha blockers have the high probability of being the 'best'.

PMID- 28756725
TI  - Human proteoforms as new targets for clinical mass spectrometry protein tests.
AB  - INTRODUCTION: Only about dozen mass spectrometry (MS) protein tests have been
      translated into clinical laboratories since the MALDI and ESI approaches were
      developed thirty years ago. While the cost and complexity of these assays are
      important factors impeding their clinical adoption, new content generated via
      proteoforms detection could provide the impetus for further development and
      translation. Areas covered: Provided here are several examples of MS-based
      protein assays capable of detecting proteoforms, including those for B-type
      natriuretic peptide (BNP) and parathyroid hormone (PTH). The evidence suggests
      that the ability to detect proteoforms is not enough to drive the clinical
      adoption of the MS-based tests - clinical utility of those proteoforms needs to
      be demonstrated first. Along those lines, recent efforts to discover, clinically
      validate, and initiate translation of novel proteoform biomarkers such as those
      of apolipoprotein C-III will be discussed. Expert commentary: MS protein tests
      face a challenging future. Both the sample preparation steps and the MS platforms
      need to be simplified to bring the cost per test down, and then the new content
      brought by the detection of proteoforms will drive the proliferation of these MS
      tests - first in clinical utility studies and then for routine diagnostics.

PMID- 28756726
TI  - Mogamulizumab for the treatment of relapsed or refractory adult T-cell leukemia
      lymphoma.
AB  - INTRODUCTION: Adult T-cell leukemia-lymphoma (ATL) is an aggressive variant of
      peripheral T-cell lymphoma of CD4+ T-malignant cells caused by human T
      lymphotropic virus type-1. Despite aggressive treatment with multidrug
      combination chemotherapies, ATL confers a poor prognosis and commonly develops
      resistance to conventional treatments. Areas covered: Mogamulizumab is a
      humanized, defucosylated monoclonal antibody that acts by targeting the CC
      chemokine receptor 4 (CCR4) on malignant cells of ATL. In phase I and II clinical
      trials, it has achieved overall response rates of 31-50% in CCR4+ malignancies.
      The most commonly observed hematologic and non-hematologic adverse events
      included lymphocytopenia, neutropenia, leukocytopenia, infusion reaction, rash,
      and pyrexia. Expert commentary: Mogamulizumab has shown significant efficacy in
      treating ATL with moderately high response rates and has been approved in Japan
      for use in ATL. It may serve as a bridge therapy to achieve disease control prior
      to allogeneic hematopoietic stem cell transplantation. It also offers potential
      for use in combination with conventional chemotherapy. Determining the optimal
      combination of mogamulizumab with conventional and novel therapies remains an
      important strategy to improve the prognosis of patients with ATL.

PMID- 28756727
TI  - Effects of m-nisoldipine on the activity and mRNA expression of four CYP isozymes
      in rats.
AB  - 1. For the first time, a systemic in vivo investigation was employed to evaluate
      the potential effects of m-nisoldipine on activities of rat cytochrome P450
      enzymes (CYP1A2, CYP2C11, CYP2D1 and CYP3A1) by both cocktail probe drugs and the
      quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR).
      2. m-Nisoldipine-treated and blank control groups were respectively administered
      m-nisoldipine at the dosage of 2.5, 5 and 12.5 mg/kg and CMC-Na solution for 15
      days consecutively, then they were given the probe drugs of caffeine, diclofenac,
      dextromethorphan and midazolam (all probes were 5 mg/kg) by p.o. The blood
      samples were collected at different times for liquid chromatography coupled with
      mass spectrometry (LC-MS) analysis. The corresponding pharmacokinetic parameters
      were applied to evaluate the effects of m-nisoldipine on the four CYP isoforms in
      vivo. In addition, RT-qPCR was performed to determine the effects of m
      nisoldipine on the mRNA expression of CYPs in rat liver. Results indicated that
      high dose and middle dose of m-nisoldipine showed significant effects on all four
      CYPs and CYP2C11, respectively. Moreover, for CYP2D1 and CYP1A2, there were no
      significant effects found at either low or middle dose of m-nisoldipine. 3. This
      study could provide not only experimental evidence for potential clinical
      application of m-nisoldipine but also a practical strategy for assessing CYP
      mediated drug-drug interactions.

PMID- 28756729
TI  - Clinical Impact of Intravascular Ultrasound Guidance During Endovascular
      Treatment of Subclavian Artery Disease.
AB  - PURPOSE: To evaluate the short- and long-term efficacy of intravascular
      ultrasound (IVUS) guidance during endovascular treatment (EVT) of subclavian
      artery disease. METHODS: The multicenter SCALLOP registry (SubClavian Artery
      disease treated with endovascuLar therapy; muLticenter retrOsPective registry)
      was interrogated to identify 542 patients who underwent successful EVT for SCAD
      between January 2003 and December 2012. Lesions were classified according to the
      use of IVUS guidance: 177 patients (mean age 68.9+/-8.6 years; 149 men) with and
      373 patients (mean age 69.9+/-8.7 years; 275 men) without. The main outcome was
      the difference in primary patency; secondary outcomes were differences in
      assisted primary patency, secondary patency, overall survival, freedom from major
      adverse cardiovascular events [MACE; all-cause mortality, myocardial infarction
      (MI), and stroke], and freedom from major adverse events (MAE). Multivariate
      analysis of the IVUS+ group was performed to identify predictors of failure;
      results are presented as the hazard ratio (HR) and 95% confidence interval (CI).
      RESULTS: In total, 538 (97.8%) lesions were treated with stents and 12 lesions by
      balloon angioplasty alone. Periprocedural and in-hospital overall complication
      rates did not differ significantly between IVUS+ (10.2%) and IVUS- (8.8%,
      p=0.617). Long-term follow-up demonstrated no significant difference between
      IVUS+ and IVUS- groups in 5-year all-cause mortality (p=0.37), MI (p=0.07),
      stroke (p=0.31), or MACE (p=0.07). However, 5-year primary patency was
      significantly higher in the IVUS+ group (88.5% vs 77.7%, p=0.03). There were no
      group differences in 5-year assisted primary patency (90.4% vs 89.9%, p=0.81) or
      secondary patency (99.4% vs 97.1%, p=0.25). Multivariate analysis of the IVUS+
      group identified in-hospital stroke (HR 16.92, 95% CI 3.60 to 79.42, p<0.01) and
      combined use of balloon-expandable and self-expanding stents (HR 5.59, 95% CI
      1.22 to 25.65, p=0.02) as independent negative predictors of primary patency.
      CONCLUSION: These results suggest that IVUS guidance can significantly improve
      long-term primary patency following endovascular treatment of subclavian artery
      disease.

PMID- 28756730
TI  - Perigraft hygroma - a rare cause of post-EVAR aneurysm growth.
AB  - Development of perigraft hygromas following repair of abdominal aortic aneurysms
      is extremely rare. A case is presented of a patient who was found to have a large
      hygroma despite two re-interventions on a previous EVAR.

PMID- 28756731
TI  - Pyrocarbon interposition arthroplasty for failed total wrist arthrodesis.

PMID- 28756728
TI  - Innovative approaches to support smoking cessation for individuals with mental
      illness and co-occurring substance use disorders.
AB  - INTRODUCTION: Tobacco remains the leading preventable cause of death in the US,
      accounting for over 520,000 deaths annually. While the smoking prevalence has
      declined over the past 50 years, those with mental illness and addictive
      disorders continue to smoke at high levels and with significant tobacco-related
      health problems. Areas covered: This review highlights the epidemiology,
      contributing factors, and evidence-base for intervening upon tobacco use in those
      with mental illness and addictive disorders. Historically underprioritized, a
      growing body of literature supports treating tobacco within mental health and
      addiction treatment settings. Critically, treating tobacco use appears to
      support, and not harm, mental health recovery and sobriety. This review also
      summarizes novel, emerging approaches to mitigate the harms of cigarette smoking.
      Expert commentary: People with mental illness and addictive disorders have a high
      prevalence of tobacco use with serious health harms. Treating tobacco use is
      essential. Evidence-based strategies include individual treatments that are stage
      matched to readiness to quit and combine cessation medications with behavioral
      therapies, supported by smoke-free policies in treatment settings and residential
      environments. Emerging approaches, with a focus on harm reduction, are electronic
      nicotine delivery systems and tobacco regulatory efforts to reduce the nicotine
      content in cigarettes, thereby reducing their addiction potential.

PMID- 28756732
TI  - Translation, cultural adaption, and test-retest reliability of Chinese versions
      of the Edinburgh Handedness Inventory and Waterloo Footedness Questionnaire.
AB  - Quantitative assessments of handedness and footedness are often required in
      studies of human cognition and behaviour, yet no reliable Chinese versions of
      commonly used handedness and footedness questionnaires are available.
      Accordingly, the objective of the present study was to translate the Edinburgh
      Handedness Inventory (EHI) and the Waterloo Footedness Questionnaire-Revised (WFQ
      R) into Mandarin Chinese and to evaluate the reliability and validity of these
      translated versions in healthy Chinese people. In the first stage of the study,
      Chinese versions of the EHI and WFQ-R were produced from a process of
      translation, back translation and examination, with necessary cultural
      adaptations. The second stage involved determining the reliability and validity
      of the translated EHI and WFQ-R for the Chinese population. One hundred and ten
      Chinese participants were tested online, and the results showed that the
      Cronbach's alpha coefficient of internal consistency was 0.877 for the translated
      EHI and 0.855 for the translated WFQ-R. Another 170 Chinese participants were
      tested and re-tested after a 30-day interval. The intra-class correlation
      coefficients showed high reliability, 0.898 for the translated EHI and 0.869 for
      the translated WFQ-R. This preliminary validation study found the translated
      versions to be reliable and valid tools for assessing handedness and footedness
      in this population.

PMID- 28756733
TI  - Relative Age Effect in Physical Fitness Among Elementary and Junior High School
      Students.
AB  - The present study investigated characteristics of the relative age effect (RAE)
      among a general sample of Japanese elementary and junior high school students.
      Japan applies a unique annual age-grouping by birthdates between April 1 and
      March 31 of the following year for sport and education. Anthropometric and
      physical fitness data were obtained from 3,610 Japanese students, including
      height, weight, the 50-m sprint, standing long jump, grip strength, bent-leg sit
      ups, sit and reach, side steps, 20-m shuttle run, and ball throw. We examined RAE
      related differences in these data using a one-way analysis of variance by
      comparing students with birthdates in the first (April-September) versus second
      (October-March of the following year) semesters. We observed a significant RAE
      for boys aged 7 to 15 years on both anthropometric and fitness data, but a
      significant RAE for girls was only evident for physical fitness tests among
      elementary school and not junior high school students. Thus, a significant RAE in
      anthropometry and physical fitness was evident in a general sample of school
      children, and there were RAE gender differences among adolescents.

PMID- 28756734
TI  - Adapting services to the needs of children and families with complex migration
      experiences: The Toulouse University Hospital's intercultural consultation.
AB  - This article presents the recently created intercultural consultation at the
      Medical and Psychological Health Care Service (CMP) of the University Hospital la
      Grave at Toulouse. The approach of the intercultural consultation was elaborated
      in response to the increasing diversity of children and families using the
      service in Toulouse. It is also based on local research that indicates the
      difficulties service providers encounter when trying to establish a solid
      therapeutic alliance with families with complex migration backgrounds who
      accumulate different disadvantaging factors. The intercultural consultation
      adapts existing models of culture-sensitive consultations in child mental health
      care in France and Canada to the local context in Toulouse. We describe the
      underlying principles of the intercultural consultation work, the therapeutic and
      mediation techniques used, and the way the work is integrated into the global
      service provision of the CMP. The process is illustrated with a case study
      followed by a discussion of the innovations.

PMID- 28756735
TI  - * Ethical Issues in the Use of Animal Models for Tissue Engineering: Reflections
      on Legal Aspects, Moral Theory, Three Rs Strategies, and Harm-Benefit Analysis.
AB  - Animal experimentation requires a solid and rational moral foundation. Objective
      and emphatic decision-making and protocol evaluation by researchers and ethics
      committees remain a difficult and sensitive matter. This article presents three
      perspectives that facilitate a consideration of the minimally acceptable standard
      for animal experiments, in particular, in tissue engineering (TE) and
      regenerative medicine. First, we review the boundaries provided by law and public
      opinion in America and Europe. Second, we review contemporary moral theory to
      introduce the Neo-Rawlsian contractarian theory to objectively evaluate the
      ethics of animal experiments. Third, we introduce the importance of available
      reduction, replacement, and refinement strategies, which should be accounted for
      in moral decision-making and protocol evaluation of animal experiments. The three
      perspectives are integrated into an algorithmic and graphic harm-benefit analysis
      tool based on the most relevant aspects of animal models in TE. We conclude with
      a consideration of future avenues to improve animal experiments.

PMID- 28756736
TI  - Prevalence of work-related musculoskeletal and non-musculoskeletal injuries in
      health care workers: the implications for work disability management.
AB  - To compare the prevalence of musculoskeletal and non-musculoskeletal injuries in
      a cohort of workers in Manitoba health care sector, who made injury claims
      between 2002 and 2012. A retrospective study, using secondary data from WCB
      Manitoba. Logistic regression was used to determine odds ratios for nature of
      work-related injuries among different groups of workers. Idiopathic work-related
      musculoskeletal disorders (WMSD) constituted 74.6% of all the injury claims.
      Injury risks varied between worker groups, and a significant difference was found
      within the female group, chi2 = 13.4, p = 0.0094, but not among the males.
      Compared to the married, single workers were more likely to experience traumatic
      than idiopathic injuries (OR = 1.72, CI, 1.28, 2.29), and much higher risk of
      traumatic injuries than non-WMSD (OR = 1.93, CI, 1.31, 2.84). Work-related injury
      risks vary significantly across occupations and worker groups, with idiopathic
      injuries being higher in high physical tasks. Practitioner Summary: To compare
      musculoskeletal and non-musculoskeletal injuries among workers in health care
      sector, and explore the implications for work disability management.
      Retrospective study, using workers' compensation claims data. The risk of
      idiopathic work-related musculoskeletal disorders continue to be high compared to
      traumatic and non-musculoskeletal disorders, particularly in tasks that involved
      high physical activities.

PMID- 28756737
TI  - * Mimicking the Biochemical and Mechanical Extracellular Environment of the
      Endochondral Ossification Process to Enhance the In Vitro Mineralization
      Potential of Human Mesenchymal Stem Cells.
AB  - Chondrogenesis and mechanical stimulation of the cartilage template are essential
      for bone formation through the endochondral ossification process in vivo. Recent
      studies have demonstrated that in vitro regeneration strategies that mimic these
      aspects separately, either chondrogenesis or mechanical stimulation, can promote
      mineralization to a certain extent both in vitro and in vivo. However, to date no
      study has sought to incorporate both the formation of the cartilage template and
      the application of mechanical stimulation simultaneously to induce osteogenesis.
      In this study, we test the hypothesis that mimicking both the biochemical and
      mechanical extracellular environment arising during endochondral ossification can
      enhance the in vitro mineralization potential of human mesenchymal stem cells
      (hMSCs). hMSC aggregates were cultured for 21 days under the following culture
      conditions; (1) Growth Medium - hydrostatic pressure (HP), (2) Chondrogenic
      Priming-HP, (3) Growth Medium + HP, and (4) Chondrogenic Priming +HP. Each group
      was then further cultured for another 21 days in the presence of osteogenic
      growth factors without HP. Biochemical (DNA, sulfate glycosaminoglycan,
      hydroxyproline, alkaline phosphatase activity, and calcium), histological (Alcian
      Blue and Alizarin Red), and immunohistological (Col I, II, and X, and BSP-2)
      analyses were conducted to investigate chondrogenic and osteogenic
      differentiation at various time points (14, 21, 35, and 42 days). Our results
      showed the application of HP-induced chondrogenesis similar to that of
      chondrogenic priming, but interestingly, there was a reduction in hypertrophy
      markers (collagen type X) by applying HP alone versus chondrogenic priming alone.
      Moreover, the results showed that both chondrogenic priming and HP in tandem
      during the priming period, followed by culture in osteogenic medium, accelerated
      the osteogenic potential of hMSCs.

PMID- 28756738
TI  - Inflammation, Stem Cells, and the Aging Hypothalamus.
AB  - The aging hypothalamus has been hypothesized to play a key role in vertebrate
      aging. Increased inflammation in microglial cells during aging reduces the number
      of neural stem cells (NSCs) in the mediobasal region of the hypothalamus. Ectopic
      brain-specific expression of SIRT1 and localized hypothalamic expression of a
      dominantly acting nuclear factor kappa-light-chain-enhancer of activated B cells
      (NF-kappaB) inhibitor to microglia or to NSCs extend life span in mice. NSCs in
      the hypothalamus secrete miRNA-containing exosomes and gonadotropin-releasing
      hormone (GnRH) that oppose aging-associated neurological and skeletomuscular
      dysfunction. These results suggest that stem cells are not mere repositories of
      future differentiated cells, but can also be active physiological effectors.
      Development of drugs that attenuate microglial inflammation and/or promoted
      maintenance of NSC viability may have significant utility for extending health
      and life span.

PMID- 28756739
TI  - Neuroanatomical correlates of donating behavior in middle childhood.
AB  - The neurobiological correlates of prosocial behavior are largely unknown. We
      examined brain structure and functional connectivity correlates of donating to a
      charity, a specific, costly, form of prosocial behavior. In 163 children,
      donating was measured using a promotional clip for a charity including a call for
      donations. Children could decide privately whether and how much they wanted to
      donate from money they had received earlier. Whole brain structural MRI scans
      were obtained to study associations between cortical thickness and donating
      behavior. In addition, resting state functional MRI scans were obtained to study
      whole brain functional connectivity and to examine functional connectivity
      between regions identified using structural MRI. In the lateral orbitofrontal
      cortex/pars orbitalis and pre-/postcentral cortex, a thicker cortex was
      associated with higher donations. Functional connectivity with these regions was
      not associated with donating behavior. These results suggest that donating
      behavior is not only situationally driven, but is also related brain morphology.
      The absence of functional connectivity correlates might imply that the
      associations with cortical thickness are involved in different underlying
      mechanisms of donating.

PMID- 28756741
TI  - Modulation of Mitochondrial DNA Copy Number to Induce Hepatocytic Differentiation
      of Human Amniotic Epithelial Cells.
AB  - Mitochondrial deoxyribonucleic acid (mtDNA) copy number is tightly regulated
      during pluripotency and differentiation. There is increased demand of cellular
      adenosine triphosphate (ATP) during differentiation for energy-intensive cell
      types such as hepatocytes and neurons to meet the cell's functional requirements.
      During hepatocyte differentiation, mtDNA copy number should be synchronously
      increased to generate sufficient ATP through oxidative phosphorylation. Unlike
      bone marrow mesenchymal cells, mtDNA copy number failed to increase by 28 days of
      differentiation of human amniotic epithelial cells (hAEC) into hepatocyte-like
      cells (HLC) despite their expression of some end-stage hepatic markers. This was
      due to higher levels of DNA methylation at exon 2 of POLGA, the mtDNA-specific
      replication factor. Treatment with a DNA demethylation agent, 5-azacytidine,
      resulted in increased mtDNA copy number, reduced DNA methylation at exon 2 of
      POLGA, and reduced hepatic gene expression. Depletion of mtDNA followed by
      subsequent differentiation did not increase mtDNA copy number, but reduced DNA
      methylation at exon 2 of POLGA and increased expression of hepatic and
      pluripotency genes. We encapsulated hAEC in barium alginate microcapsules and
      subsequently differentiated them into HLC. Encapsulation resulted in no net
      increase of mtDNA copy number but a significant reduction in DNA methylation of
      POLGA. RNAseq analysis showed that differentiated HLC express hepatocyte-specific
      genes but also increased expression of inflammatory interferon genes.
      Differentiation in encapsulated cells showed suppression of inflammatory genes as
      well as increased expression of genes associated with hepatocyte function
      pathways and networks. This study demonstrates that an increase in classical
      hepatic gene expression can be achieved in HLC through encapsulation, although
      they fail to effectively regulate mtDNA copy number.

PMID- 28756740
TI  - C-Type lectin receptor(s)-targeted nanoliposomes: an intelligent approach for
      effective cancer immunotherapy.
AB  - AIM: The purpose of present approach is to target C-Type lectin (CTL) receptors
      for preferential uptake by the macrophages/dendritic cells and improving the
      cross-presentation of ovalbumin. MATERIALS & METHODS: Conventional and engineered
      nanoliposomes (MPNLs) were fabricated and extensively characterized. The
      nanoliposome(s) was spherical in shape; and their zeta potential, size and
      ovalbumin loading efficiency were recorded to be 268 +/- 4.15 nm, 23.4 +/- 0.35
      mV, 46.65 +/- 1.84%, respectively. RESULTS: The findings demonstrate that MPNLs
      significantly improved the antigen uptake and its cross-presentation to evoke Th
      CD8+ cell-mediated cellular immunity. CONCLUSION: In a nutshell, this engineered
      approach mannose surface modification for active targeting to dendritic
      cells/macrophages and pH-dependent quick endosomal antigen release is a promising
      system for efficient cancer immunotherapy.

PMID- 28756743
TI  - Over-expression, characterization, and modification of highly active alkaline
      phosphatase from a Shewanella genus bacterium.
AB  - We isolated a Shewanella sp. T3-3 bacterium that yielded highly active alkaline
      phosphatase (APase). We then cloned the APase gene from Shewanella sp. T3-3 (T3
      3AP), and expressed and purified the enzyme from Escherichia coli. Recombinant T3
      3AP showed high comparative reactivity on colorimetric (pNPP) and luminescent
      substrates (PPD and ASP-5). Subsequently, we improved the residual activity after
      maleimide activation by introducing amino acid substitutions of two Lys residues
      that were located near the active site. The double mutant enzyme (K161S + K184S)
      showed much higher residual specific activity after maleimide activation than the
      wild type enzyme, and had approximately twofold increased sensitivity on sandwich
      enzyme linked immunosorbent assays (ELISA) compared with calf intestinal APase
      (CIAP), which is routinely used as a labeling enzyme for ELISA.

PMID- 28756742
TI  - Pentablock copolymer dexamethasone nanoformulations elevate MYOC: in vitro
      liberation, activity and safety in human trabecular meshwork cells.
AB  - AIM: The aim of this study is to examine the elevation of MYOC in long-term
      treatment of human trabecular meshwork (HTM) cells using dexamethasone (DEX)
      encapsulated pentablock (PB) copolymer-based nanoparticles (NPs) (DEX-PB-NPs).
      MATERIALS & METHODS: PB copolymers and DEX-PB-NPs were synthesized and
      characterized using nuclear magnetic resonance, gel permeation chromatography,
      and X-ray diffraction analyses. MYOC levels secreted from HTM cells were measured
      by western blot (WB) analysis. RESULTS: DEX-PB-NPs were formulated in the size
      range of 109 +/- 3.77 nm (n = 3). A long term DEX release from the NPs was
      observed over three months. Cell viability and cytotoxicity were not affected up
      to 12 weeks of treatment with PB-copolymer or DEX-PB-NPs. WB data from five HTM
      cell strains showed that MYOC levels increased by 5.2 +/- 1.3, 7.4 +/- 4.3, and
      2.8 +/- 1.1-fold in the presence of DEX-PB-NPs compared with 9.2 +/- 3.8, 2.2 +/-
      0.5, and 1.5 +/- 0.3-fold at 4, 8 and 12 weeks in control-DEX treatment group,
      respectively (n = 5). Based on the decline in MYOC levels after withdrawal of DEX
      from control wells, DEX-PB-NPs released the DEX for at least 10 weeks.
      CONCLUSION: The treatment of HTM cells using DEX-PB-NPs were analyzed in this
      study. The in vitro cell-based system developed here is a valuable tool for
      determining the safety and effects of steroids released from polymeric NPs.

PMID- 28756744
TI  - Personalized, bilateral whole-body somatosensory cortex stimulation to relieve
      fatigue in multiple sclerosis.
AB  - BACKGROUND: The patients suffering from multiple sclerosis (MS) often consider
      fatigue the most debilitating symptom they experience, but conventional medicine
      currently offers poorly efficacious therapies. OBJECTIVE: We executed a
      replication study of an innovative approach for relieving MS fatigue. METHODS:
      According to the sample size estimate, we recruited 10 fatigued MS patients who
      received 5-day transcranial direct current stimulation (tDCS) in a randomized,
      double-blind, Sham-controlled, crossover study, with modified Fatigue Impact
      Scale (mFIS) score reduction at the end of the treatment as primary outcome. A
      personalized anodal electrode, shaped on the magnetic resonance imaging (MRI)
      derived individual cortical folding, targeted the bilateral whole-body primary
      somatosensory cortex (S1) with an occipital cathode. RESULTS: The amelioration of
      fatigue symptoms after Real stimulation (40% of baseline) was significantly
      larger than after Sham stimulation (14%, p = 0.012). Anodal whole body S1 induced
      a significant fatigue reduction in mildly disabled MS patients when the fatigue
      related symptoms severely hampered their quality of life. CONCLUSION: This second
      result in an independent group of patients supports the idea that neuromodulation
      interventions that properly select a personalized target might be a suitable non
      pharmacological treatment for MS fatigue.

PMID- 28756745
TI  - Misrecollection prevents older adults from benefitting from semantic relatedness
      of the memoranda in associative memory.
AB  - Memory for episodic associations declines in aging, ostensibly due to decreased
      recollection abilities. Accordingly, associative unitization - the encoding of
      associated items as one integrated entity - may potentially attenuate age-related
      associative deficits by enabling familiarity-based retrieval, which is relatively
      preserved in aging. To test this hypothesis, we induced bottom-up unitization by
      manipulating semantic relatedness between memoranda. Twenty-four young and 24
      older adults studied pairs of object pictures that were either semantically
      related or unrelated. Participants subsequently discriminated between intact,
      recombined and new pairs. We found that semantic relatedness increased the
      contributions of both familiarity and recollection in young adults, but did not
      improve older adults' performance. Instead, they showed associative deficits,
      driven by increased recollection-based false recognition. This may reflect a
      "misrecollection" phenomenon, in which older adults make more false alarms to
      recombined pairs with particularly high confidence, due to poorer retrieval
      monitoring regarding semantically-related associative probes.

PMID- 28756746
TI  - Nordic Walking Can Be Incorporated in the Exercise Prescription to Increase
      Aerobic Capacity, Strength, and Quality of Life for Elderly: A Systematic Review
      and Meta-Analysis.
AB  - The aim of this systematic review and meta-analysis was to summarize and analyze
      the effects of Nordic Walking on physical fitness, body composition, and quality
      of life in the elderly. Keyword "Nordic Walking" associated with "elderly" AND/OR
      "aging" AND/OR "old subjects" AND/OR "aged" AND/OR "older adults" were used in
      the online database MEDLINE, Embase, PubMed, Scopus, PsycINFO, and SPORTDiscus.
      Only studies written in English language and published in peer-reviewed journals
      were considered. A meta-analysis was performed and effect sizes calculated.
      Fifteen studies were identified; age of participants ranged from 60 to 92 years
      old. Comparing with a sedentary group, effect sizes showed that Nordic Walking
      was able to improve dynamic balance (0.30), functional balance (0.62), muscle
      strength of upper (0.66) and lower limbs (0.43), aerobic capacity (0.92),
      cardiovascular outcomes (0.23), body composition (0.30), and lipid profile
      (0.67). It seemed that Nordic Walking had a negative effect on static balance (
      0.72). Comparing with a walking (alone) training, effect sizes showed that Nordic
      Walking improved the dynamic balance (0.30), flexibility of the lower body
      (0.47), and quality of life (0.53). Walking training was more effective in
      improving aerobic capacity (-0.21). Comparing Nordic Walking with resistance
      training, effect sizes showed that Nordic Walking improved dynamic balance
      (0.33), muscle strength of the lower body (0.39), aerobic capacity (0.75),
      flexibility of the upper body (0.41), and the quality of life (0.93). Nordic
      Walking can be considered as a safe and accessible form of aerobic exercise for
      the elderly population, able to improve cardiovascular outcomes, muscle strength,
      balance ability, and quality of life.

PMID- 28756747
TI  - NAMPT-Mediated NAD Biosynthesis as the Internal Timing Mechanism: In NAD+ World,
      Time Is Running in Its Own Way.
AB  - The biological age of organisms differs from the chronological age and is
      determined by internal aging clock(s). How cells estimate time on a scale of 24
      hours is relatively well studied; however, how biological time is measured by
      cells, tissues, organs, or organisms in longer time periods (years and decades)
      is largely unknown. What is clear and widely agreed upon is that the link to age
      and age-related diseases is not chronological, as it does not depend on a fixed
      passage of time. Rather, this link depends on the biological age of an individual
      cell, tissue, organ, or organism and not on time in a strictly chronological
      sense. Biological evolution does not invent new methods as often as improving
      upon already existing ones. It should be easier to evolve and remodel the
      existing (circadian) time clock mechanism to use it for measurement or regulation
      of longer time periods than to invent a new time mechanism/clock. Specifically,
      it will be demonstrated that the circadian clock can also be used to regulate
      circannual or even longer time periods. Nicotinamide phosphoribosyltransferase
      (NAMPT)-mediated nicotinamide adenine dinucleotide (NAD+) levels, being regulated
      by the circadian clock, might be the missing link between aging, cell cycle
      control, DNA damage repair, cellular metabolism and the aging clock, which is
      responsible for the biological age of an organism. The hypothesis that
      NAMPT/NAD+/SIRT1 might represent the time regulator that determines the
      organismal biological age will be presented. The biological age of tissues and
      organs might be regulated and synchronized through eNAMPT blood secretion. The
      "NAD World 2.0" concept will be upgraded with detailed insights into mechanisms
      that regulate NAD+-mediated aging clock ticking, the duration and amplitude of
      which are responsible for the aging rate of humans.

PMID- 28756748
TI  - * The New Zealand White Rabbit as a Model for Preclinical Studies Addressing
      Tissue Repair at the Level of the Abdominal Wall.
AB  - In this report, we review the use of the New Zealand White rabbit as the
      experimental animal for several models of abdominal wall repair. For the repair
      of an abdominal wall defect, such as a hernia in clinical practice, multiple
      types of prosthetic material exist. Before their marketing, each of these
      biomaterials needs to be tested in a preclinical setting to confirm its
      biocompatibility and appropriate behavior at the different tissue interfaces. For
      preclinical trials, we have always used the New Zealand White rabbit as the model
      owing to its ease of handling and suitable size. This size allows for
      laparoscopic studies designed to follow the behavior in real time of a
      biomaterial implanted at the peritoneal interface, a delicate interface that
      often gives rise to complications in human practice. The size of the rabbit also
      offers a sufficiently large number of implant samples to be harvested for a
      complete battery of tests at several time points postimplant. In this review, we
      first describe the models established and then provide the results obtained so
      far using these models to test the different types of biomaterial. We end our
      review with a discussion of the clinical implications of these results.

PMID- 28756749
TI  - Research roundup.
AB  - Synopses of a selection of recently published research articles of relevance to
      palliative care.

PMID- 28756751
TI  - Politics and palliative care: Burkina Faso.
AB  - Dion Smyth's review of palliative nursing on the internet.

PMID- 28756750
TI  - Specialist palliative care nursing and the philosophy of palliative care: a
      critical discussion.
AB  - Nursing is the largest regulated health professional workforce providing
      palliative care across a range of clinical settings. Historically, palliative
      care nursing has been informed by a strong philosophy of care which is soundly
      articulated in palliative care policy, research and practice. Indeed, palliative
      care is now considered to be an integral component of nursing practice regardless
      of the specialty or clinical setting. However, there has been a change in the way
      palliative care is provided. Upstreaming and mainstreaming of palliative care and
      the dominance of a biomedical model with increasing medicalisation and
      specialisation are key factors in the evolution of contemporary palliative care
      and are likely to impact on nursing practice. Using a critical reflection of the
      authors own experiences and supported by literature and theory from seminal texts
      and contemporary academic, policy and clinical literature, this discussion paper
      will explore the influence of philosophy on nursing knowledge and theory in the
      context of an evolving model of palliative care.

PMID- 28756752
TI  - Experiences of patient-family caregiver dyads in palliative care during hospital
      to-home transition process.
AB  - BACKGROUND: there are many people with advanced cancer who are cared for in the
      community, though little is known about patients' and family members' lived
      experiences during discharge from hospital to home. OBJECTIVES: to describe the
      experiences of the patient-family caregiver dyad during the transition from
      hospital to home at a National Cancer Institute in Colombia. METHODS: a
      descriptive phenomenological approach was taken for this study. RESULTS: Forty
      one nominal codes emerged, comprising seven themes that describe the experience
      of the individual in palliative care and their family caregiver during the
      transition from hospital to home care. CONCLUSIONS: the patient-family caregiver
      dyad have to deal with symptoms while being confronted with the prognosis and
      progression of the disease at home. The economic costs in acquiring supplies
      needed for proper care provision are considerable. In addition there are
      administrative fees from consultations and accessing the health services.
      Emotional and spiritual support for the dyad is required.

PMID- 28756753
TI  - Palliative care and nursing support for patients experiencing dyspnoea.
AB  - To investigate the association between the type of support provided by nurses for
      dyspnoea and palliative care practice in Japan, a cross-sectional questionnaire
      survey was conducted in 2015. Of the 535 questionnaires sent to nurses working at
      22 designated cancer hospitals, 344 were returned. The questionnaire assessed the
      demographic characteristics of the nurses, nursing support for dyspnoea, and
      palliative care practice measured by the 'Palliative care self-reported practices
      scale'. Multivariate analysis showed that the domains of palliative care practice
      influenced the provision of nursing support for patients with dyspnoea. In
      conclusion, palliative care practice is important for supporting patients with
      dyspnoea, and nurses should possess the requisite knowledge and skills to deliver
      this care appropriately.

PMID- 28756754
TI  - Never say die: death euphemisms, misunderstandings and their implications for
      practice.
AB  - BACKGROUND: A Massive Open Online Course (MOOC) on death and dying was conducted
      to open the dialogue around death and dying. In one activity, participants were
      asked to engage with language and to think of alternative words (or euphemisms)
      that are used to describe death. AIM: To reflect from a nursing perspective how
      language enables and sometimes disguises important messages and conversations.
      METHODS: Four hundred and seventy one participants provided 3053 euphemisms.
      FINDINGS: Euphemisms were varied, with many providing commentary on their purpose
      and use. DISCUSSION: As a society we have become quite creative in the use of
      euphemisms, but need to be mindful of misunderstandings and misinterpretations
      which can cause embarrassment and distress in clinical situations. CONCLUSION:
      This paper describes some of the euphemisms that were provided, examining why
      they are used and how their use can be easily misconstrued in daily life and in
      clinical practice.

PMID- 28756755
TI  - When a patient asks you to pray: what's a provider to do?

PMID- 28756756
TI  - Knowing me, knowing you.

PMID- 28756757
TI  - Challenges of treating a patient living with lymphoedema and advancing disease.

PMID- 28756758
TI  - Sex difference in types and distribution of risk factors in ischemic and
      hemorrhagic stroke.
AB  - Background Stroke is the second leading cause of death worldwide and is
      associated with several risk factors with variable risk factor distribution by
      population. We report the types and frequency of the associated factors of stroke
      in north Iran. Methods Consecutive patients with stroke were recruited from 2014
      to 2015. The two groups of ischemic and hemorrhagic stroke were compared with
      respect to age, sex, the prevalence, and distribution of the risk factors.
      Results Among 230 patients (84.3% ischemic stroke) with mean age of 61.2 years,
      hypertension (73%), diabetes mellitus (53%), cardiovascular disease (51%), and
      dyslipidemia (47%) were the most frequent risk factors. Hypertension was
      significantly more prevalent in males compared with females (88% vs. 60%, OR =
      4.91, 95% CI: 2.48-9.71). Hypertension, smoking, and opioid consumption were
      associated with hemorrhagic stroke. Dyslipidemia was significantly higher in
      ischemic stroke (OR = 2.65, 95% CI: 1.21-5.8). Overall, 84.3% of stroke occurred
      in patients aged >50 years (92.8% of women vs. 74.5% of the men, OR = 4.43, 95%
      CI: 1.93-10.16, p = 0.001). Conclusion Stroke was more prevalent in females;
      hypertension was more prevalent in males. In the age group less than 50 years
      old, stroke is more prevalent in men.

PMID- 28756759
TI  - Differential characteristics, stroke recurrence, and predictors of covert atrial
      fibrillation of embolic strokes of undetermined source.
AB  - Background and purpose Identifying embolic strokes of undetermined source (ESUS)
      patients likely to harbor atrial fibrillation may have diagnostic and therapeutic
      implications. Our aim was to examine differences between ESUS and cardioembolic
      strokes, to evaluate stroke recurrence rate among ESUS and to identify baseline
      characteristics of ESUS patients who were later diagnosed with atrial
      fibrillation. Materials and methods We assessed all ischemic stroke patients
      admitted between June 2012 and November 2013. ESUS were compared to cardioembolic
      strokes at discharge. After at least 12-month follow-up, ESUS patients diagnosed
      with atrial fibrillation were compared to those who remained as ESUS. Results
      There were 236 ischemic strokes, 32.6% were ESUS. Compared to cardioembolic
      strokes, ESUS were younger (p < 0.0001), had milder strokes (p < 0.05), less
      prevalence of hypertension (p < 0.05), peripheral vascular disease (p < 0.05),
      and previous ischemic stroke (p < 0.05). After follow-up, 15% of ESUS patients
      had stroke recurrences and 12% evidenced paroxysmal atrial fibrillation. ESUS
      patients diagnosed with atrial fibrillation in the follow-up were older (p <
      0.0001), had higher erythrocyte sedimentation rate (p < 0.05), and were more
      likely to have >=2 infarcts in the same arterial territory in the initial
      magnetic resonance imaging (p < 0.05). Conclusions Older age, small-scattered
      infarcts on initial magnetic resonance imaging and high erythrocyte sedimentation
      rate levels appear to identify ESUS patients more likely to be diagnosed of
      atrial fibrillation during follow-up.

PMID- 28756760
TI  - Spray Delivery of Intestinal Organoids to Reconstitute Epithelium on
      Decellularized Native Extracellular Matrix.
AB  - The native extracellular matrix (ECM) serves as a unique platform for tissue
      engineering because it provides an organ-specific scaffold in terms of both
      matrix composition and tissue architecture. However, efficacious cell-seeding
      techniques for recellularizing the ECM constructs with appropriate cell types to
      restore biological function remain under development. In this study, the impact
      of spraying as a seeding technique for repopulation of decellularized small
      intestine was investigated. In a series of experiments, CaCo-2 cells were first
      used to investigate the effect of spray device type and pressure on cell
      viability and to optimize parameters for seeding intestinal epithelial cells.
      High cell viability and a homogeneous cell distribution were obtained when cell
      suspensions were sprayed through an airbrush at low pressure. Next, the effect of
      seeding method and spray pressure on the size and dispersal of intestinal
      organoids, a more complex and clinically relevant intestinal stem cell
      population, was evaluated. The feasibility of seeding intestinal epithelial cells
      onto decellularized scaffolds was next studied using sprayed CaCo-2 cells, which
      survived the spray-seeding process and formed a monolayer on the scaffold.
      Finally, airbrush seeding was used to spray intestinal organoids onto the
      scaffolds, with cell survival and tissue architecture evaluated after 1 week of
      culture. Organoids seeded through pipetting onto the decellularized scaffold
      survived, but demonstrated aggregation, with cells organized around multiple
      small lumens. In contrast, organoids airbrush spray seeded at 0.35 bar onto the
      decellularized scaffold not only engrafted but also demonstrated formation of an
      epithelial monolayer that resembled the absorptive surface found on intestinal
      villi. The results suggest that seeding cells through airbrush spraying holds
      great potential for use in tissue engineering, especially for large-scale tubular
      organ recellularization.

PMID- 28756761
TI  - Measuring maternal serum screening markers for Down's syndrome in plasma
      collected for cell-free DNA testing.
AB  - Objectives To determine whether maternal plasma collected in cell-free DNA
      stabilizing tubes is suitable for measuring prenatal screening 'serum' markers.
      Methods Matched plasma and serum samples were collected from 41 second trimester
      and 42 first trimester non-Down's syndrome pregnancies. Second trimester samples
      were tested for alpha-fetoprotein, unconjugated estriol, human chorionic
      gonadotropin, and inhibin-A (Beckman Coulter DxI immunoassay). First trimester
      samples were tested for human chorionic gonadotropin and pregnancy-associated
      plasma protein A. Method comparisons performed for each marker compared plasma
      and serum results. Down's syndrome likelihood ratios in serum and plasma were
      compared. Results Plasma and serum results for all markers were highly correlated
      ( r > 0.983) but for all, plasma results differed, usually by proportional
      amounts. After conversion to multiples of the median using sample type-specific
      medians, the logarithmic standard deviations in serum and plasma did not differ
      (all p > 0.37). Likelihood ratios for the first and second trimester marker
      combinations were highly correlated and closely agreed (log likelihood ratios
      range 1.005 to 1.032; 1.000 indicates complete agreement). Conclusions These
      results using specialized plasma collection tubes are similar to those of our
      earlier study showing that plasma collected in EDTA tubes is suitable for 'serum'
      Down's syndrome screening. Laboratories must account for proportional changes by
      computing new plasma medians or modifying existing serum medians. Using a portion
      of the plasma from cell-free DNA collection tubes for 'serum screening' may have
      an advantage in programmes that are reflexively testing cell-free DNA, as only
      one sample type need be collected.

PMID- 28756762
TI  - Update on the prevention of death from ruptured abdominal aortic aneurysm.
AB  - Objectives To monitor the early effect of a national population screening
      programme for abdominal aortic aneurysm in 65-year-old men. Setting The study
      used national statistics for death rates from abdominal aortic aneurysm (Office
      of National Statistics) and hospital admission data in England (Hospital Episode
      Statistics). Methods Information concerning deaths from abdominal aortic aneurysm
      (ruptured and non-ruptured) (1999-2014) and hospital admissions for ruptured
      abdominal aortic aneurysm (2000-2015) was examined. Results The absolute number
      of deaths from abdominal aortic aneurysm in men and women aged 65 and over has
      decreased by around 30% from 2001 to 2014, but as the population has increased,
      the relative reduction was 45.6% and 40.0%, respectively. Some 65% of all
      abdominal aortic aneurysm deaths are in men aged over 65; women aged 65 and over
      account for around 31%. Deaths from ruptured abdominal aortic aneurysm in men
      aged 60-74 (the screened group) appear to be declining at the same rate as in men
      aged 75 and over. The relative decline in admissions to hospital with ruptured
      abdominal aortic aneurysm may be greater in men and women aged 60-74 (which
      contains the screened group of men), than those older, giving the first possible
      evidence that abdominal aortic aneurysm screening is having an effect. Conclusion
      The death rate from abdominal aortic aneurysm is declining rapidly in England.
      There is the first evidence that screening may be contributing to this reduction.

PMID- 28756763
TI  - The effect of omitting an early population-based vision screen in the
      Netherlands: A micro-simulation model approach.
AB  - Objective To estimate the effect of omitting an individual screen from a child
      vision screening programme on the detection of amblyopia in the Netherlands. A
      previous study (Rotterdam Amblyopia Screening Effectiveness Study) suggested that
      the three screens carried out between 6 and 24 months contributed little. Methods
      We developed a micro-simulation model that approximated the birth-cohort data
      from the previous study, in which 2964 children had completed follow-up at age 7,
      and 100 amblyopia cases were detected. Detailed data on screens, referrals, and
      orthoptic follow-up, including the cause of amblyopia, were available. The model
      predicted the number of amblyopia cases detected for each screen and for the
      entire screening programme, and the effect of omitting screens. Incidence curves
      for all types of amblyopia caused by strabismus, refractive anomalies or by both
      were estimated by approximation of the observational data, in conjunction with
      experts' estimations and the literature. Results We calculated mean actual
      sensitivity per screen per type of amblyopia, and the effect per screen.
      Screening at 24 months was found to be least effective. The impact on the
      screening programme, estimated by summing the effectiveness per screen, omitting
      the 24-month screen, was a reduction of 3.4% (57 vs. 59 cases) in the number of
      detected cases of amblyopia at age 5. Conclusion The effectiveness of the Dutch
      vision screening programme would hardly be affected by omission of the 24-month
      screening examination. A disinvestment study is warranted.

PMID- 28756764
TI  - "Promoting Early Presentation" intervention sustains increased breast cancer
      awareness in older women for three years: A randomized controlled trial.
AB  - Objective In a randomized controlled trial, the Promoting Early Presentation
      intervention increased older women's breast cancer awareness after two years. We
      investigated whether this increase was sustained at three years, and the effect
      on breast screening self-referral. Methods We randomly allocated 867 women
      attending their final invited breast screening appointment to the Promoting Early
      Presentation intervention or usual care. We examined breast cancer awareness
      after three years and breast screening self-referrals after four years. Results
      Women in the Promoting Early Presentation intervention arm had higher breast
      cancer awareness at three years than the usual care arm (odds ratio: 10.4; 95%
      confidence interval: 3.1 to 34.8). There were no differences in proportions self
      referring for breast screening between arms, but statistical power was limited.
      Conclusion The Promoting Early Presentation intervention has a sustained effect
      on breast cancer awareness in older women. The effect on self-referral for breast
      screening is unclear.

PMID- 28756765
TI  - Targeted therapeutic mild hypercapnia after cardiac arrest.

PMID- 28756766
TI  - Accuracy assessment of measuring component position after total ankle
      arthroplasty using a conventional method.
AB  - BACKGROUND: This study was to assess the accuracy of measuring the tibial and
      talar components position and to investigate the outlier rate of each component
      and predisposing factors related to component malalignment after total ankle
      arthroplasty (TAA) using a conventional method. METHODS: One hundred fifty
      consecutive primary total ankle arthroplasty were performed using the three
      component HINTEGRA prosthesis for ankle end-stage osteoarthritis. Radiographic
      analysis for the accuracy of component position in coronal and sagittal plane was
      conducted at postoperative 6 months. Additionally, the accuracy of component
      position was evaluated according to presence of preoperative deformity or joint
      incongruency. RESULTS: The mean postoperative coronal angles of the tibial and
      talar components (alpha and gamma) were 91.9 degrees  and 91.3 degrees . The mean
      postoperative sagittal angles of the tibial and talar components (beta and delta
      angle) were 84.6 degrees  and 91.7 degrees . In the coronal plane, 16 (10.7%)
      tibial components and 15 (10.0%) talar components showed outliers greater than 5
      degrees . In sagittal plane, 15 (10.0%) tibial components and 29 (19.3%) talar
      components showed outliers greater than 5 degrees . There was no meaningful
      increase of the outlier rate regarding presence of preoperative deformity or
      joint incongruency. CONCLUSIONS: In conventional method of TAA, the outlier rate
      of the tibial and talar components was about 10 to 20%, especially, the outlier
      rate of talar component in sagittal plane was up to 20%. Therefore, careful
      attention should be paid to implant the talar component in conventional TAA.

PMID- 28756767
TI  - Beyond pilotitis: taking digital health interventions to the national level in
      China and Uganda.
AB  - BACKGROUND: Innovation theory has focused on the adoption of new products or
      services by individuals and their market-driven diffusion to the population at
      large. However, major health sector innovations typically emerge from
      negotiations between diverse stakeholders who compete to impose or at least
      prioritise their preferred version of that innovation. Thus, while many digital
      health interventions have succeeded in terms of adoption by a substantial number
      of providers and patients, they have generally failed to gain the level of
      acceptance required for their integration into national health systems that would
      promote sustainability and population-wide application. The area of innovation
      considered here relates to a growing number of success stories that have created
      considerable enthusiasm among donors, international agencies, and governments for
      the potential role of ICTs in transforming weak national health information
      systems in middle and low income countries. This article uses a case study
      approach to consider the assumptions, institutional as well as technical,
      underlying this enthusiasm and explores possible ways in which outcomes might be
      improved. METHODS: Literature review and case study analysis. RESULTS: The two
      systems considered have had considerable success in terms of gaining and
      maintaining government support and addressing the concerns of providers without
      compromising their core elements. In Uganda, the system has flourished in spite
      of severe resource constraints, using a participatory approach that has
      encouraged a high level of community engagement. In China, concern with past
      failures generated the political will to build a high quality surveillance
      system, using the latest technology and drawing on a highly skilled human
      resource base. CONCLUSIONS: Both example stress the importance of recognising the
      political, social and historical context within which information systems have to
      function. Implementers need to focus as much on the perceptions, attitudes and
      needs of stakeholders as on the technology. Implementers should distinguish
      between factors which may influence engagement at an institutional level and
      those aimed at supporting and supervising individuals within those institutions.
      Finally, we would suggest that designing interoperability into systems at the
      outset, rather than assuming that this can be achieved at some point in the
      future, may prove far easier in the longer term.

PMID- 28756768
TI  - Care at a non-university hospital: an independent risk factor for mortality in
      ARDS?

PMID- 28756769
TI  - Continuous glucose monitoring in the ICU: clinical considerations and consensus.
AB  - Glucose management in intensive care unit (ICU) patients has been a matter of
      debate for almost two decades. Compared to intermittent monitoring systems,
      continuous glucose monitoring (CGM) can offer benefit in the prevention of severe
      hyperglycemia and hypoglycemia by enabling insulin infusions to be adjusted more
      rapidly and potentially more accurately because trends in glucose concentrations
      can be more readily identified. Increasingly, it is apparent that a single
      glucose target/range may not be optimal for all patients at all times and, as
      with many other aspects of critical care patient management, a personalized
      approach to glucose control may be more appropriate. Here we consider some of the
      evidence supporting different glucose targets in various groups of patients,
      focusing on those with and without diabetes and neurological ICU patients. We
      also discuss some of the reasons why, despite evidence of benefit, CGM devices
      are still not widely employed in the ICU and propose areas of research needed to
      help move CGM from the research arena to routine clinical use.

PMID- 28756770
TI  - Synthetic lethal short hairpin RNA screening reveals that ring finger protein 183
      confers resistance to trametinib in colorectal cancer cells.
AB  - BACKGROUND: The mitogen-activated extracellular signal-regulated kinase 1/2
      (MEK1/2) inhibitor trametinib has shown promising therapeutic effects on
      melanoma, but its efficacy on colorectal cancer (CRC) is limited. Synthetic
      lethality arises with a combination of two or more separate gene mutations that
      causes cell death, whereas individual mutations keep cells alive. This study
      aimed to identify the genes responsible for resistance to trametinib in CRC
      cells, using a synthetic lethal short hairpin RNA (shRNA) screening approach.
      METHODS: We infected HT29 cells with a pooled lentiviral shRNA library and
      applied next-generation sequencing to identify shRNAs with reduced abundance
      after 8-day treatment of 20 nmol/L trametinib. HCT116 and HT29 cells were used in
      validation studies. Stable ring finger protein 183 (RNF183)-overexpressing cell
      lines were generated by pcDNA4-myc/his-RNF183 transfection. Stable RNF183
      knockdown cell lines were generated by infection of lentiviruses that express
      RNF183 shRNA, and small interference RNA (siRNA) was used to knock down RNF183
      transiently. Quantitative real-time PCR was used to determine the mRNA
      expression. Western blotting, immunohistochemical analysis, and enzyme-linked
      immunosorbent assay (ELISA) were used to evaluate the protein abundance. MTT
      assay, colony formation assay, and subcutaneous xenograft tumor growth model were
      used to evaluate cell proliferation. RESULTS: In the primary screening, we found
      that the abundance of RNF183 shRNA was markedly reduced after treatment with
      trametinib. Trametinib induced the expression of RNF183, which conferred
      resistance to drug-induced cell growth repression and apoptotic and non-apoptotic
      cell deaths. Moreover, interleukin-8 (IL-8) was a downstream gene of RNF183 and
      was required for the function of RNF183 in facilitating cell growth.
      Additionally, elevated RNF183 expression partly reduced the inhibitory effect of
      trametinib on IL-8 expression. Finally, xenograft tumor model showed the
      synergism of RNF183 knockdown and trametinib in repressing the growth of CRC
      cells in vivo. CONCLUSION: The RNF183-IL-8 axis is responsible for the resistance
      of CRC cells to the MEK1/2 inhibitor trametinib and may serve as a candidate
      target for combined therapy for CRC.

PMID- 28756771
TI  - Prognostic role of ABO blood type in patients with extranodal natural killer/T
      cell lymphoma, nasal type: a triple-center study.
AB  - BACKGROUND: The prognostic significance of ABO blood type for lymphoma is largely
      unknown. We evaluated the prognostic role of ABO blood type in patients with
      extranodal natural killer (NK)/T-cell lymphoma (ENKTL). METHODS: We
      retrospectively analyzed clinical data of 697 patients with newly diagnosed ENKTL
      from three cancer centers. The prognostic value of ABO blood type was evaluated
      using Kaplan-Meier curves and Cox proportional hazard models. The prognostic
      values of the International Prognostic Index (IPI) and the Korean Prognostic
      Index (KPI) were also evaluated. RESULTS: Compared with patients with blood type
      O, those with blood type non-O tended to display elevated baseline serum C
      reactive protein levels (P = 0.038), lower rate of complete remission (P =
      0.005), shorter progression-free survival (PFS, P < 0.001), and shorter overall
      survival (OS, P = 0.001). Patients with blood type O/AB had longer PFS (P <
      0.001) and OS (P = 0.001) compared with those with blood type A/B. Multivariate
      analysis demonstrated that age >60 years (P < 0.001), mass >=5 cm (P = 0.001),
      stage III/IV (P < 0.001), elevated serum lactate dehydrogenase (LDH) levels (P =
      0.001), and blood type non-O were independent adverse predictors of OS (P =
      0.001). ABO blood type was found to be superior to both the IPI in discriminating
      patients with different outcomes in the IPI low-risk group and the KPI in
      distinguishing between the intermediate-to-low- and high-to-intermediate-risk
      groups. CONCLUSIONS: ABO blood type was an independent predictor of clinical
      outcome for patients with ENKTL.

PMID- 28756772
TI  - Giant mucinous adenocarcinoma of the appendix: a case report.
AB  - BACKGROUND: Appendiceal mucinous adenocarcinoma is an extremely rare disease in
      clinical practice. Here, we report a case of unprecedented size that occupied the
      entire abdomen of a man. CASE PRESENTATION: A 49-year-old Chinese Han man
      presented with symptoms of abdominal distension. During a computed tomography
      imaging examination, a cystic-solid mass that occupied his entire abdominal
      cavity was detected. During exploratory laparotomy, an appendiceal tumor in his
      abdominal-pelvic cavity measuring 27.6 * 14.2 cm was found, and he underwent
      tumor resection. The pathology of the tumor identified a well-differentiated
      appendiceal mucinous adenocarcinoma with mucin infiltrating into the soft tissue
      of the lump edge and omentum tissue. After surgery, our patient accepted
      intraperitoneal infusion chemotherapy. At present, he has had no recurrence for
      15 months. CONCLUSIONS: To the best of our knowledge, the present case is the
      largest appendiceal mucinous adenocarcinoma reported. Surgical tumor resection is
      the preferred treatment for appendiceal mucinous adenocarcinoma. This is
      supplemented by chemotherapy which can further prolong survival.

PMID- 28756773
TI  - Genomic technologies-from tools to therapies.

PMID- 28756774
TI  - Heart failure hospitalization risk associated with use of two classes of oral
      antidiabetic medications: an observational, real-world analysis.
AB  - BACKGROUND: Newer oral antidiabetic drug classes are expanding treatment options
      for type 2 diabetes mellitus (T2DM); however, concerns remain. The objective was
      to assess relative risk of heart failure hospitalization of sodium-glucose co
      transporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP4) inhibitors in T2DM
      patients. METHODS: This retrospective observational study used a national
      commercially insured claims database. Adults (>18 years) with T2DM newly starting
      SGLT2 or DPP4 medication between April 2013 and December 2014 were included.
      Depending on their index fill, patients were grouped into either SGLT2 or DPP4
      medication class cohorts. The primary outcome was hospitalization for heart
      failure and the risk was assessed using Cox regression models. Propensity score
      matching (1:2 ratio) was used to adjust for potential confounders. Analyses were
      also stratified by the presence of baseline diabetes complication and age (<65 vs
      65+). RESULTS: The matched cohort included 4899 SGLT2 and 9798 DPP4 users. The
      risk of heart failure hospitalization was lower among SGLT2 users in comparison
      with matched DPP4 users (2.0% SGLT2 vs 3.1% DPP4; adjusted hazard ratio [aHR]
      0.68; 95% confidence interval [CI] 0.54-0.86; p = .001). However, the stratified
      analyses revealed no risk difference among the majority of the analyzed patients,
      i.e., those aged <65, which comprised 85% of the matched cohort (aHR = 0.78; 95%
      CI 0.57-1.05; p = .09), and those without prior complication, which comprised 69%
      of matched cohort (aHR = 0.83; 95% CI 0.54-1.27; p = 0.40). CONCLUSIONS: In this
      real-life analysis, the rate of hospitalizations for heart failure was
      significantly lower for patients initiating an SGLT2 compared with a DPP4
      medication, specifically among older patients and those with diabetes
      complication.

PMID- 28756776
TI  - The cross-national epidemiology of social anxiety disorder: Data from the World
      Mental Health Survey Initiative.
AB  - BACKGROUND: There is evidence that social anxiety disorder (SAD) is a prevalent
      and disabling disorder. However, most of the available data on the epidemiology
      of this condition originate from high income countries in the West. The World
      Mental Health (WMH) Survey Initiative provides an opportunity to investigate the
      prevalence, course, impairment, socio-demographic correlates, comorbidity, and
      treatment of this condition across a range of high, middle, and low income
      countries in different geographic regions of the world, and to address the
      question of whether differences in SAD merely reflect differences in threshold
      for diagnosis. METHODS: Data from 28 community surveys in the WMH Survey
      Initiative, with 142,405 respondents, were analyzed. We assessed the 30-day, 12
      month, and lifetime prevalence of SAD, age of onset, and severity of role
      impairment associated with SAD, across countries. In addition, we investigated
      socio-demographic correlates of SAD, comorbidity of SAD with other mental
      disorders, and treatment of SAD in the combined sample. Cross-tabulations were
      used to calculate prevalence, impairment, comorbidity, and treatment. Survival
      analysis was used to estimate age of onset, and logistic regression and survival
      analyses were used to examine socio-demographic correlates. RESULTS: SAD 30-day,
      12-month, and lifetime prevalence estimates are 1.3, 2.4, and 4.0% across all
      countries. SAD prevalence rates are lowest in low/lower-middle income countries
      and in the African and Eastern Mediterranean regions, and highest in high income
      countries and in the Americas and the Western Pacific regions. Age of onset is
      early across the globe, and persistence is highest in upper-middle income
      countries, Africa, and the Eastern Mediterranean. There are some differences in
      domains of severe role impairment by country income level and geographic region,
      but there are no significant differences across different income level and
      geographic region in the proportion of respondents with any severe role
      impairment. Also, across countries SAD is associated with specific socio
      demographic features (younger age, female gender, unmarried status, lower
      education, and lower income) and with similar patterns of comorbidity. Treatment
      rates for those with any impairment are lowest in low/lower-middle income
      countries and highest in high income countries. CONCLUSIONS: While differences in
      SAD prevalence across countries are apparent, we found a number of consistent
      patterns across the globe, including early age of onset, persistence, impairment
      in multiple domains, as well as characteristic socio-demographic correlates and
      associated psychiatric comorbidities. In addition, while there are some
      differences in the patterns of impairment associated with SAD across the globe,
      key similarities suggest that the threshold for diagnosis is similar regardless
      of country income levels or geographic location. Taken together, these cross
      national data emphasize the international clinical and public health significance
      of SAD.

PMID- 28756775
TI  - The house spider genome reveals an ancient whole-genome duplication during
      arachnid evolution.
AB  - BACKGROUND: The duplication of genes can occur through various mechanisms and is
      thought to make a major contribution to the evolutionary diversification of
      organisms. There is increasing evidence for a large-scale duplication of genes in
      some chelicerate lineages including two rounds of whole genome duplication (WGD)
      in horseshoe crabs. To investigate this further, we sequenced and analyzed the
      genome of the common house spider Parasteatoda tepidariorum. RESULTS: We found
      pervasive duplication of both coding and non-coding genes in this spider,
      including two clusters of Hox genes. Analysis of synteny conservation across the
      P. tepidariorum genome suggests that there has been an ancient WGD in spiders.
      Comparison with the genomes of other chelicerates, including that of the newly
      sequenced bark scorpion Centruroides sculpturatus, suggests that this event
      occurred in the common ancestor of spiders and scorpions, and is probably
      independent of the WGDs in horseshoe crabs. Furthermore, characterization of the
      sequence and expression of the Hox paralogs in P. tepidariorum suggests that many
      have been subject to neo-functionalization and/or sub-functionalization since
      their duplication. CONCLUSIONS: Our results reveal that spiders and scorpions are
      likely the descendants of a polyploid ancestor that lived more than 450 MYA.
      Given the extensive morphological diversity and ecological adaptations found
      among these animals, rivaling those of vertebrates, our study of the ancient WGD
      event in Arachnopulmonata provides a new comparative platform to explore common
      and divergent evolutionary outcomes of polyploidization events across eukaryotes.

PMID- 28756779
TI  - Quality improvement primer part 1: Preparing for a quality improvement project in
      the emergency department.
AB  - Emergency medicine (EM) providers work in a fast-paced and often hectic
      environment that has a high risk for patient safety incidents and gaps in the
      quality of care. These challenges have resulted in opportunities for frontline EM
      providers to play a role in quality improvement (QI) projects. QI has developed
      into a mature field with methodologies that can dramatically improve the odds of
      having a successful project with a sustainable impact. However, this expertise is
      not yet commonly taught during professional training. In this first of three
      articles meant as a QI primer for EM clinicians, we will introduce QI methodology
      and strategic planning using a fictional case study as an example. We will review
      how to identify a QI problem, define components of an effective problem
      statement, and identify stakeholders and core change team members. We will also
      describe three techniques used to perform root cause analyses-Ishikawa diagrams,
      Pareto charts and process mapping-and how they relate to preparing for a QI
      project. The next two papers in this series will focus on the execution of the QI
      project itself using rapid-cycle testing and on the evaluation and sustainability
      of QI projects.

PMID- 28756780
TI  - AN INTEGRATED PERSPECTIVE ON THE ASSESSMENT OF TECHNOLOGIES: INTEGRATE-HTA.
AB  - OBJECTIVES: Current health technology assessment (HTA) is not well equipped to
      assess complex technologies as insufficient attention is being paid to the
      diversity in patient characteristics and preferences, context, and
      implementation. Strategies to integrate these and several other aspects, such as
      ethical considerations, in a comprehensive assessment are missing. The aim of the
      European research project INTEGRATE-HTA was to develop a model for an integrated
      HTA of complex technologies. METHODS: A multi-method, four-stage approach guided
      the development of the INTEGRATE-HTA Model: (i) definition of the different
      dimensions of information to be integrated, (ii) literature review of existing
      methods for integration, (iii) adjustment of concepts and methods for assessing
      distinct aspects of complex technologies in the frame of an integrated process,
      and (iv) application of the model in a case study and subsequent revisions.
      RESULTS: The INTEGRATE-HTA Model consists of five steps, each involving
      stakeholders: (i) definition of the technology and the objective of the HTA; (ii)
      development of a logic model to provide a structured overview of the technology
      and the system in which it is embedded; (iii) evidence assessment on
      effectiveness, economic, ethical, legal, and socio-cultural aspects, taking
      variability of participants, context, implementation issues, and their
      interactions into account; (iv) populating the logic model with the data
      generated in step 3; (v) structured process of decision-making. CONCLUSIONS: The
      INTEGRATE-HTA Model provides a structured process for integrated HTAs of complex
      technologies. Stakeholder involvement in all steps is essential as a means of
      ensuring relevance and meaningful interpretation of the evidence.

PMID- 28756781
TI  - Self-Complexity and Perceived Self-Aspect Control in Post-Traumatic Stress
      Disorder.
AB  - BACKGROUND: Post-traumatic stress disorder often brings about profound, lasting,
      structural changes to one's sense of self. AIMS: This study investigated self
      complexity and self-aspect control in post-traumatic stress disorder (PTSD).
      METHOD: Trauma survivors with (n = 103) and without (n = 102) PTSD completed an
      online questionnaire which involved the completion of a self-complexity task and
      measures of PTSD. RESULTS: It was found that those with PTSD had significantly
      greater overall self-complexity than those without PTSD. Furthermore, when
      considering self-description valence, it was found that those with PTSD had
      significantly greater negative self-complexity than those without PTSD, but the
      groups did not differ in terms of positive self-complexity. Second, those with
      PTSD reported significantly less control over their self-aspects. Third, for
      those with PTSD, lower levels of self-aspect control were significantly
      correlated with greater negative self-complexity and lower positive self
      complexity. Finally, self-aspect control mediated the relationship between self
      complexity and PTSD symptoms. CONCLUSION: The theoretical implications for PTSD
      models and the clinical implications for the treatment of those with PTSD are
      explored.

PMID- 28756778
TI  - A systematic review and meta-analysis comparing mortality in pre-hospital
      tracheal intubation to emergency department intubation in trauma patients.
AB  - BACKGROUND: Pre-hospital endotracheal intubation is frequently used for trauma
      patients in many emergency medical systems. Despite a wide range of publications
      in the field, it is debated whether the intervention is associated with a
      favourable outcome, when compared to more conservative airway measures. METHODS:
      A systematic literature search was conducted to identify interventional and
      observational studies where the mortality rates of adult trauma patients
      undergoing pre-hospital endotracheal intubation were compared to those undergoing
      emergency department intubation. RESULTS: Twenty-one studies examining 35,838
      patients were included. The median mortality rate in patients undergoing pre
      hospital intubation was 48% (range 8-94%), compared to 29% (range 6-67%) in
      patients undergoing intubation in the emergency department. Odds ratios were in
      favour of emergency department intubation both in crude and adjusted mortality,
      with 2.56 (95% CI: 2.06, 3.18) and 2.59 (95% CI: 1.97, 3.39), respectively. The
      overall quality of evidence is very low. Twelve of the twenty-one studies found a
      significantly higher mortality rate after pre-hospital intubation, seven found no
      significant differences, one found a positive effect, and for one study an
      analysis of the mortality rate was beyond the scope of the article. CONCLUSIONS:
      The rationale for wide and unspecific indications for pre-hospital intubation
      seems to lack support in the literature, despite several publications involving a
      relatively large number of patients. Pre-hospital intubation is a complex
      intervention where guidelines and research findings should be approached
      cautiously. The association between pre-hospital intubation and a higher
      mortality rate does not necessarily contradict the importance of the
      intervention, but it does call for a thorough investigation by clinicians and
      researchers into possible causes for this finding.

PMID- 28756782
TI  - Is food store type associated with the consumption of ultra-processed food and
      drink products in Brazil?
AB  - OBJECTIVE: To analyse the association between food store type and the consumption
      of ultra-processed products in Brazil. DESIGN: Data from the 2008-2009 Household
      Budget Survey involving a probabilistic sample of 55 970 Brazilian households.
      Food stores were grouped into nine categories. Foods and drinks were grouped
      according to characteristics of food processing. The contribution of each food
      store type to the total energy acquired from each food processing group, and
      according to quintiles of consumption of ultra-processed products, was estimated.
      Exploratory factor analysis was conducted to identify a pattern of food store
      usage. Linear regression models were performed to estimate the relationship
      between the purchase pattern and the consumption of ultra-processed products.
      RESULTS: In line with their larger market share, supermarkets accounted for 59 %
      of total energy and participated most in acquisition for three food groups, with
      emphasis on ultra-processed products (60.4 % of energy). The participation of
      supermarkets in total purchase tended to increase in populations with higher
      consumption of ultra-processed products, while the participation of small markets
      and small producers tended to decrease. The purchase pattern characterized by use
      of traditional retail (street fairs and vendors, small markets, small farmers,
      butcheries) was associated with a smaller consumption of ultra-processed
      products. CONCLUSIONS: Food policies and interventions aiming to reduce the
      consumption of ultra-processed products should consider the influence of
      supermarkets on the consumption of these products. A purchase pattern based on
      traditional retail constitutes an important tool for promoting healthy eating in
      Brazil.

PMID- 28756777
TI  - Genomic innovations, transcriptional plasticity and gene loss underlying the
      evolution and divergence of two highly polyphagous and invasive Helicoverpa pest
      species.
AB  - BACKGROUND: Helicoverpa armigera and Helicoverpa zea are major caterpillar pests
      of Old and New World agriculture, respectively. Both, particularly H. armigera,
      are extremely polyphagous, and H. armigera has developed resistance to many
      insecticides. Here we use comparative genomics, transcriptomics and resequencing
      to elucidate the genetic basis for their properties as pests. RESULTS: We find
      that, prior to their divergence about 1.5 Mya, the H. armigera/H. zea lineage had
      accumulated up to more than 100 more members of specific detoxification and
      digestion gene families and more than 100 extra gustatory receptor genes,
      compared to other lepidopterans with narrower host ranges. The two genomes remain
      very similar in gene content and order, but H. armigera is more polymorphic
      overall, and H. zea has lost several detoxification genes, as well as about 50
      gustatory receptor genes. It also lacks certain genes and alleles conferring
      insecticide resistance found in H. armigera. Non-synonymous sites in the expanded
      gene families above are rapidly diverging, both between paralogues and between
      orthologues in the two species. Whole genome transcriptomic analyses of H.
      armigera larvae show widely divergent responses to different host plants,
      including responses among many of the duplicated detoxification and digestion
      genes. CONCLUSIONS: The extreme polyphagy of the two heliothines is associated
      with extensive amplification and neofunctionalisation of genes involved in host
      finding and use, coupled with versatile transcriptional responses on different
      hosts. H. armigera's invasion of the Americas in recent years means that
      hybridisation could generate populations that are both locally adapted and
      insecticide resistant.

PMID- 28756783
TI  - Pork products associated with human infection caused by an emerging phylotype of
      hepatitis E virus in England and Wales.
AB  - Since 2010, human hepatitis E infections have increased in England and Wales.
      Most cases are locally acquired and caused by hepatitis E virus genotype 3 (HEV
      G3). HEV G3 is linked to the consumption of pork products. The increase is
      associated with the emergence of a new phylotype, HEV G3-group 2 (G3-2, also
      known as G3abcdhij). Sixty individuals with confirmed hepatitis E infection and
      no history of travel outside the UK were recruited: 19 were infected with HEV G3
      group 1 (G3-1 or G3efg) and 41 with G3-2. Epidemiological data relating to usual
      shopping habits and consumption of ham and sausages were analysed together with
      typing data to identify any associations with HEV phylotype. Study participants
      who purchased ham and/or sausage from a major supermarket were more likely to
      have HEV G3-2 infection (Relative risks 1.85, P = 0.06, CI 0.97-3.53). The HEV G3
      2 phylotype has not been detected in indigenous UK pigs and it is suggested that
      human infections could be the result of consumption of products made from pork
      originating outside the UK. This does not infer blame on the supermarket but the
      epidemiology of HEV is dynamic and reflects complex animal husbandry practices
      which need to be explored further.

PMID- 28756784
TI  - Factors associated with continued participation in a matched monetary incentive
      programme at local farmers' markets in low-income neighbourhoods in San Diego,
      California.
AB  - OBJECTIVE: The Farmers' Market Fresh Fund Incentive Program is a policy, systems
      and environmental intervention to improve access to fresh produce for
      participants on governmental assistance in the USA. The current study examined
      factors associated with ongoing participation in this matched monetary incentive
      programme. DESIGN: Relationship of baseline factors with number of Fresh Fund
      visits was assessed using Poisson regression. Mixed-effects modelling was used to
      explore changes in consumption of fruits and vegetables and diet quality.
      SETTING: San Diego, California. SUBJECTS: Recipients of Supplemental Nutrition
      Assistance Program (SNAP), Special Supplemental Nutrition Program for Women,
      Infants, and Children (WIC) and Supplemental Security Income (SSI) who attended
      participating farmers' markets from 2010 to 2012 (n 7298). RESULTS: Among those
      with participation for <=6 months, factors associated with increased visits
      included reporting more daily servings of fruits and vegetables (F&V) at
      baseline, being Vietnamese or Asian/Pacific Islander, and eligibility because of
      SNAP/CalFresh or SSI (v. WIC). Among those who came for 6-12 months, being
      Asian/Pacific Islander, eligibility because of SNAP/CalFresh and enrolling in the
      autumn, winter or spring were associated with a greater number of Fresh Fund
      visits. Among those who came for >12 months, being male and eligibility because
      of SSI were associated with a greater number of visits. Overall, the odds of
      increasing number of servings of F&V consumed increased by 2 % per month, and the
      odds of improved perception of diet quality increased by 10 % per month.
      CONCLUSIONS: Sustaining and increasing Fresh Fund-type programme operations
      should be a top priority for future policy decisions concerning farmers' market
      use in low-income neighbourhoods.

PMID- 28756785
TI  - IMPACT OF HEALTH TECHNOLOGY ASSESSMENT IN LITIGATION CONCERNING ACCESS TO HIGH
      COST DRUGS.
AB  - OBJECTIVES: The impact of health technology assessment (HTA) in the
      judicialization of the right of health has not been deeply studied in Latin
      American countries. The purpose of this study is to review the process of
      judicialization of the access to high cost drugs in Uruguay and assess the impact
      HTAs have had on this process. METHODS: The methodology used for this study
      included a comprehensive literature search in electronic databases, local
      journals, internal documents developed in the Ministry of Health, as well as
      conducting interviews with key informants. RESULTS: Judicialization of the access
      of high cost drugs has been increasing since 2010. The strategy of the Ministry
      of Health of Uruguay to decrease this problem included the organization of
      roundtables with judges and other stakeholders on the basis of HTA, the training
      of defense lawyers in the use and interpretation of HTA, and the participation of
      a professional who develops HTA in the preparation of the defense arguments. A
      year after the implementation of this strategy, 25 percent of writs of protection
      were won by the Ministry of Health. CONCLUSIONS: Even though the strategy
      implemented was effective in reducing the loss of litigations, it was not
      effective in reducing the growing number of writs of protection. It is essential
      to address this problem in a broad debate and to promote understanding between
      the parties.

PMID- 28756786
TI  - Negative latent tuberculosis at time of incarceration: identifying a very high
      risk group for infection.
AB  - The main aim was to measure the incidence of latent tuberculosis infection (LTBI)
      and identify risk factors associated with infection. In addition, we determined
      the number needed to screen (NNS) to identify LTBI and active tuberculosis. We
      followed 129 prisoners for 2 years following a negative two-step tuberculin skin
      test (TST). The cumulative incidence of TST conversion over 2 years was 29.5%
      (38/129), among the new TST converters, nine developed active TB. Among persons
      with no evidence of LTBI, the NNS to identify a LTBI case was 3.4 and an active
      TB case was 14.3. The adjusted risk factors for LTBI conversion were
      incarceration in prison number 1, being formerly incarcerated, and overweight. In
      conclusion, prisoners have higher risk of LTBI acquisition compared with high
      risk groups, such as HIV-infected individuals and children for whom LTBI testing
      should be performed according to World Health Organization guidance. The high
      conversion rate is associated with high incidence of active TB disease, and
      therefore we recommend mandatory LTBI screening at the time of prison entry.
      Individuals with a negative TST at the time of entry to prison are at high risk
      of acquiring infection, and should therefore be followed in order to detect
      convertors and offer LTBI treatment. This approach has a very low NNS for each
      identified case, and it can be utilized to decrease development of active TB
      disease and transmission.

PMID- 28756787
TI  - Brief Behavioural Activation (Brief BA) for Adolescent Depression: A Pilot Study.
AB  - BACKGROUND: Depression in adolescence is a common and serious mental health
      problem. In the UK, access to evidence-based psychological treatments is limited,
      and training and employing therapists to deliver these is expensive. Brief
      behavioural activation for the treatment of depression (BATD) has great potential
      for use with adolescents and to be delivered by a range of healthcare
      professionals, but there is limited empirical investigation with this group.
      AIMS: To adapt BATD for depressed adolescents (Brief BA) and conduct a pilot
      study to assess feasibility, acceptability and clinical effectiveness. METHOD:
      Twenty depressed adolescents referred to the local NHS Child and Adolescent
      Mental Health service (CAMHs) were offered eight sessions of Brief BA followed by
      a review around one month later. Self- and parent-reported routine outcome
      measures (ROMs) were collected at every session. RESULTS: Nineteen of the 20
      young people fully engaged with the treatment and all reported finding some
      aspect of Brief BA helpful. Thirteen (65%) required no further psychological
      intervention following Brief BA, and both young people and parents reported high
      levels of acceptability and satisfaction with the approach. The pre-post effect
      size of Brief BA treatment was large. CONCLUSIONS: Brief BA is a promising
      innovation in the treatment of adolescent depression. This approach requires
      further evaluation to establish effectiveness and cost effectiveness compared
      with existing evidence-based treatments for adolescent depression. Other
      questions concern the effectiveness of delivery in other settings and when
      delivered by a range of professionals.

PMID- 28756788
TI  - What is good communication for people living with dementia? A mixed-methods
      systematic review.
AB  - BACKGROUND: Many strategies have been recommended to support caregivers in
      communicating with people who live with dementia. However, less is known about
      what makes communication a good and meaningful experience from the perspective of
      people with dementia. Understanding this may enhance the person with dementia's
      sense of connectedness, strengthen their relationships, and facilitate person
      centered care. The current review aimed to evaluate research that examined
      experiences of communication in people living with dementia. Studies that
      examined reports provided by people with dementia, healthcare professionals, and
      family caregivers were included. METHODS: A mixed-methods systematic review was
      conducted using PsychINFO, MEDLINE, and EMBASE databases. RESULTS: After applying
      the eligibility criteria, 15 studies were included. Although eight of these
      recruited people with dementia, only one focused on their perspectives of
      communication experiences and the remaining studies focused on the perspectives
      of family caregivers and healthcare professionals. These studies either explored
      experiences without suggestions of communication methods, "open exploration," or
      through examining experiences of strategies, "exploration of strategies." A
      significant theme was around communication difficulties that affected
      interpersonal relationships and activities of daily living. Conversely,
      personhood strategies and a strong underlying relationship were believed to
      facilitate communication. The one study that examined the perspectives of people
      with dementia emphasized the importance of retaining valued relationships and
      feeling respected during communication. CONCLUSIONS: The need to involve people
      with dementia in research, particularly around their experiences of
      communication, is evident. Such research would be imperative for facilitating
      person-centered care, strengthening social relationships, and informing training
      programs.

PMID- 28756789
TI  - Antibiotic Overuse is a Major Risk Factor for Clostridium difficile Infection in
      Surgical Patients.
AB  - Clostridium difficile infection (CDI) is associated with increased cost,
      morbidity, and mortality in postoperative patients. Variable rates of
      postoperative CDI are reported among 4 surgical specialties during the 30-month
      study period. Risk factors for CDI include antibiotic use, increased ASA score,
      and increased admissions in the past year. Infect Control Hosp Epidemiol
      2017;38:1254-1257.

PMID- 28756790
TI  - Psychometric Properties of the Brief Version of the Social Skills Inventory for
      Adolescents.
AB  - The present study aimed to evaluate the evidence of internal structure and scores
      reliability of the Social Skills Inventory for adolescents - brief version (IHSA
      Del-Prette). The following analyses were performed: (1) Exploratory Factor
      Analysis - EFA; (2) Confirmatory Factor Analysis - CFA; (3) Reliability; (4)
      Multigroup Analysis (invariance). The participants were 2,291 students of the
      Middle and High Schools, both sexes aged 12 to 17 years old divided into two
      sample groups: 1,172 participants in sample group 1 (collected 2006-2007) and
      1,119 in sample group 2 (collected 2011-2012). The results of the EFA (group 1)
      support the four subscales structure (Self-control, Affective Approach, Empathy
      and Assertiveness) for 16 items (loadings > .30). The structure was confirmed by
      the CFA performed on the second group (CFI = .96, TLI = .95, RMSEA = .05, 90% CI
      [.04, .05], loadings > .50); and showed scalar invariance (samples 1 and 2) due
      to group and age, as well as partial scalar invariance due to gender (DeltaCFI <
      .01; DeltaNCI < .02). It was concluded the brief version of IHSA-Del-Prette
      presents psychometric properties for use in the Brazilian context.

PMID- 28756791
TI  - SMARTPHONE REMINDER FOR PHYSICAL ACTIVITY IN PEOPLE WITH INTELLECTUAL
      DISABILITIES.
AB  - Several studies have been carried out regarding different interventions in an
      effort to improve levels of physical activity in people with an intellectual
      disability (ID). Studies have been carried out regarding physical activity
      interventions (1), educational interventions (2), and multimodal interventions
      (3). New technologies are currently being used to carry out changes in daily
      habits and to promote health in different pathologies but not in people with an
      ID (4;5). Due to the poor maintenance of physical activity that we have found in
      people with ID, the objective of the present study is to determine the
      maintenance of levels of physical activity, quality of life, self-efficacy, and
      social support in this population through an intervention with an application in
      their smartphones.

PMID- 28756792
TI  - Does being a Stranger make it Difficult to Cooperate?
AB  - Competition and cooperation are two somewhat opposed strategies for interpersonal
      social interaction that help us to achieve both individual and shared goals. The
      main aim of this study was to explore which type of social interaction
      (cooperative or competitive) is more stressful in a face-to-face same-sex dyad in
      healthy young participants (n = 178), considering outcome obtained in these tasks
      (positive or negative) and sex as moderating variables, and performance of the
      task alone as a control condition. Salivary cortisol (Csal) was measured in one
      sample obtained before task and four obtained after the task (+0, +15, +30 and
      +45 minutes after). Anxiety-state was assessed before and immediately after the
      task. Participants who cooperated and obtained negative outcomes had higher Csal
      levels than those who worked alone with negative outcomes in all periods after
      the task (p = .008, eta p 2 = .058 and p = .033, eta p 2 = .031, respectively).
      Moreover, those who cooperated showed higher mean self-reported state anxiety
      levels than the rest of the participants (p = .013, eta p 2 = .051 and p < .001,
      eta p 2 = .530, respectively). Our study indicates that cooperation between
      strangers in face-to-face dyads is highly stressful, more so than competing or
      working alone. These results should be taken into account for understanding
      situations of social stress and can be generalized to situations in which
      subjects cooperate or must decide between cooperating and competing to attain a
      goal.

PMID- 28756793
TI  - Contribution of scaling up nutrition Academic Platforms to nutrition capacity
      strengthening in Africa: local efforts, continental prospects and challenges.
AB  - Addressing contemporary nutrition problems often requires application of
      knowledge from multiple disciplines. The scaling up nutrition (SUN) movement
      harnesses multiple sectors for effective global and in-country planning and
      implementation. Although the role of knowledge networks (academia and research
      institutions) is recognised, the how of engaging knowledge networks in the
      current SUN architecture is only now becoming apparent. For relevant sectors to
      play their roles effectively, observed capacity gaps, particularly in developing
      country settings, need to be addressed. The present paper presents the work being
      undertaken by the Ghana SUN Academic Platform (AP), a local knowledge network,
      towards strengthening nutrition capacity in Ghana. The AP presently provides
      technical support, evidence and capacity towards scaling up effective nutrition
      interventions in Ghana and beyond. The data presented draws heavily on the
      observations and collective experiences of the authors in practice, complemented
      by a review of relevant literature. The ultimate goal of the AP is to build
      capacity of professionals from nutrition and cognate sectors (including planning,
      agriculture, health, economics, research and academia). This is an essential
      ingredient for effective and durable SUN efforts. The paper recognises that both
      disciplinary and interdisciplinary capacity is required for effective SUN efforts
      in Africa, and offers an approach that utilises cross-sector/inter-professional,
      peer-learning and experiential learning initiatives.

PMID- 28756794
TI  - Psychometric Properties of the Worry Behaviors Inventory: Replication and
      Extension in a Large Clinical and Community Sample.
AB  - BACKGROUND: The use of maladaptive behaviors by individuals with generalized
      anxiety disorder (GAD) is theoretically important and clinically meaningful.
      However, little is known about the specificity of avoidant behaviors to GAD and
      how these behaviors can be reliably assessed. AIMS: This study replicated and
      extended the psychometric evaluation of the Worry Behaviors Inventory (WBI), a
      brief self-report measure of avoidant behaviors associated with GAD. METHOD: The
      WBI was administered to a hospital-based sample of adults seeking treatment for
      symptoms of anxiety and/or depression (n = 639) and to a community sample (n =
      55). Participants completed measures of symptom severity (GAD, depression, panic
      disorder, health anxiety, and personality disorder), and measures of checking,
      reassurance-seeking and behavioral inhibition. Analyses evaluated the factor
      structure, convergent, divergent, incremental, and discriminant validity, as well
      the temporal stability and treatment sensitivity of the WBI. RESULTS: The two
      factor structure found in the preliminary psychometric evaluation of the WBI was
      replicated. The WBI was sensitive to changes across treatment and correlated well
      with measures of GAD symptom severity and maladaptive behaviors. The WBI was more
      strongly related to GAD symptom severity than other disorders. The WBI
      discriminated between clinical and community samples. CONCLUSIONS: The WBI
      provides clinicians and researchers with a brief, clinically meaningful index of
      problematic behaviors that may guide treatment decisions and contribute to our
      understanding of maintaining factors in GAD.

PMID- 28756796
TI  - Identification of Keywords From Twitter and Web Blog Posts to Detect Influenza
      Epidemics in Korea.
AB  - OBJECTIVE: Social media data are a highly contextual health information source.
      The objective of this study was to identify Korean keywords for detecting
      influenza epidemics from social media data. METHODS: We included data from
      Twitter and online blog posts to obtain a sufficient number of candidate
      indicators and to represent a larger proportion of the Korean population. We
      performed the following steps: initial keyword selection; generation of a keyword
      time series using a preprocessing approach; optimal feature selection; model
      building and validation using least absolute shrinkage and selection operator,
      support vector machine (SVM), and random forest regression (RFR). RESULTS: A
      total of 15 keywords optimally detected the influenza epidemic, evenly
      distributed across Twitter and blog data sources. Model estimates generated using
      our SVM model were highly correlated with recent influenza incidence data.
      CONCLUSIONS: The basic principles underpinning our approach could be applied to
      other countries, languages, infectious diseases, and social media sources. Social
      media monitoring using our approach may support and extend the capacity of
      traditional surveillance systems for detecting emerging influenza. (Disaster Med
      Public Health Preparedness. 2018; 12: 352-359).

PMID- 28756795
TI  - CURRENT ENVIRONMENT FOR INTRODUCING HEALTH TECHNOLOGY ASSESSMENT IN GREECE.
AB  - OBJECTIVES: The aim of this study was to describe the current regulatory
      environment in Greece to evaluate the potential introduction of health technology
      assessment (HTA) for medicinal products for human use. METHODS: Data sources
      consist of national legislation on pricing and reimbursement of health
      technologies to identify the potential need of establishing HTA and its relevant
      structure. RESULTS: The pricing procedure regarding medicinal products for human
      use is based on an external reference pricing mechanism which considers the
      average of the three lowest Euorpean Union prices. Currently, a formal HTA
      procedure has not been applied in Greece, and the only prerequisite used for the
      reimbursement of medicinal products for human use is their inclusion in the
      Positive Reimbursement List. To restrict pharmaceutical expenditure, a variety of
      measures-such as clawback mechanisms, rebates, monthly budget caps per physician,
      generics penetration targeting-have been imposed, aiming mainly to regulate the
      price level rather than control the introduction of medicinal products for human
      use in the Greek pharmaceutical market. CONCLUSIONS: Greece has the opportunity
      to rapidly build capacity, implement, and take advantage of the application of
      HTA mechanisms by clearly defining the goals, scope, systems, context,
      stakeholders, and methods that will be involved in the local HTA processes,
      taking into account the country's established e-prescription system and the
      recently adapted legislative framework.

PMID- 28756797
TI  - Early enrichment in free-range laying hens: effects on ranging behaviour, welfare
      and response to stressors.
AB  - Free-range laying hen systems are increasing within Australia. The pullets for
      these systems are typically reared indoors before being provided first range
      access around 21 to 26 weeks of age. Thus, the rearing and laying environments
      are disparate and hens may not adapt well to free-range housing. In this study,
      we reared 290 Hy-Line(r) Brown day-old chicks divided into two rooms each with
      feed, water and litter. In the enriched room, multiple structural, manipulable,
      visual and auditory stimuli were also provided from 4 to 21 days, the non
      enriched room had no additional objects or stimuli. Pullets were transferred to
      the laying facility at 12 weeks of age and divided into six pens (three enriched
      reared, three non-enriched-reared) with identical indoor resources and outdoor
      range area. All birds were first provided range access at 21 weeks of age. Video
      observations of natural disturbance behaviours on the range at 22 to 23 and 33 to
      34 weeks of age showed no differences in frequency of disturbance occurrences
      between treatment groups (P=0.09) but a decrease in disturbance occurrences over
      time (P<0.0001). Radio-frequency identification tracking of individually tagged
      birds from 21 to 37 weeks of age showed enriched birds on average, spent less
      time on the range each day (P<0.04) but with a higher number of range visits than
      non-enriched birds from 21 to 24 weeks of age (P=0.01). Enriched birds accessed
      the range on more days (P=0.03) but over time, most birds in both treatment
      groups accessed the range daily. Basic external health scoring showed minimal
      differences between treatment groups with most birds in visibly good condition.
      At 38 weeks of age all birds were locked inside for 2 days and from 40 to 42
      weeks of age the outdoor range was reduced to 20% of its original size to
      simulate stressful events. The eggs from non-enriched birds had higher
      corticosterone concentrations following lock-in and 2 weeks following range
      reduction compared with the concentrations within eggs from enriched birds
      (P<0.0001). Correspondingly, the enriched hens showing a greater increase in the
      number of visits following range area reduction compared to non-enriched hens
      (P=0.02). Only one rearing room per treatment was used but these preliminary data
      indicate 3 weeks of early enrichment had some long-term effects on hen ranging
      behaviour and enhanced hen's adaptability to environmental stressors.

PMID- 28756799
TI  - The future of emergency medicine in Canada: Reflections one year after the
      release of the Collaborative Working Group final report.

PMID- 28756798
TI  - Guidance when Applying the Canadian Triage and Acuity Scale (CTAS) to the
      Geriatric Patient: Executive Summary.

PMID- 28756800
TI  - Revisions to the Canadian Emergency Department Triage and Acuity Scale (CTAS)
      Guidelines 2016.

PMID- 28756801
TI  - Emergency Medicine Training and Practice in Canada: Celebrating the Past &
      Evolving for the Future.

PMID- 28756802
TI  - Risk Factors for Surgical Site Infections Following Neurosurgical Spinal Fusion
      Operations: A Case-Control Study-Methodological issue.

PMID- 28756803
TI  - The Iowa Disinfection Cleaning Project: Opportunities, Successes, and Challenges
      of a Structured Intervention Program in 56 Hospitals.
AB  - OBJECTIVE A diverse group of hospitals in Iowa implemented a program to
      objectively evaluate and improve the thoroughness of disinfection cleaning of
      near-patient surfaces. Administrative benefits of, challenges of, and impediments
      to the program were also evaluated. METHODS We conducted a prospective, quasi
      experimental pre-/postintervention trial to improve the thoroughness of terminal
      room disinfection cleaning. Infection preventionists utilized an objective
      cleaning performance monitoring system (DAZO) to evaluate the thoroughness of
      disinfection cleaning (TDC) expressed as a proportion of objects confirmed to
      have been cleaned (numerator) to objects to be cleaned per hospital policy
      (denominator)*100. Data analysis, educational interventions, and objective
      performance feedback were modeled on previously published studies using the same
      monitoring tool. Programmatic analysis utilized unstructured and structured
      information from participants irrespective of whether they participated in the
      process improvement aspects to the program. RESULTS Initially, the overall TDC
      was 61% in 56 hospitals. Hospitals completing 1 or 2 feedback cycles improved
      their TDC percentages significantly (P90% for at least 38 months. A survey of
      infection preventionists found that lack of time and staff turnover were the most
      common reasons for terminating the study early. CONCLUSION The study confirmed
      that hospitals using this program can improve their TDC percentages
      significantly. Hospitals must invest resources to improve cleaning and to sustain
      their gains. Infect Control Hosp Epidemiol 2017;38:960-965.

PMID- 28756804
TI  - Concerns Associated With Cleaning Robotic Surgical Instruments-Response to
      Wallace.

PMID- 28756805
TI  - Burden of Clostridium difficile Infections in French Hospitals in 2014 From the
      National Health Insurance Perspective.
AB  - OBJECTIVE To describe the hospital stays of patients with Clostridium difficile
      infection (CDI) and to measure the hospitalization costs of CDI (as primary and
      secondary diagnoses) from the French national health insurance perspective DESIGN
      Burden of illness study SETTING All acute-care hospitals in France METHODS Data
      were extracted from the French national hospitalization database (PMSI) for
      patients covered by the national health insurance scheme in 2014.
      Hospitalizations were selected using the International Classification of
      Diseases, 10 th revision (ICD-10) code for CDI. Hospital stays with CDI as the
      primary diagnosis or the secondary diagnosis (comorbidity) were studied for the
      following parameters: patient sociodemographic characteristics, mortality, length
      of stay (LOS), and related costs. A retrospective case-control analysis was
      performed on stays with CDI as the secondary diagnosis to assess the impact of
      CDI on the LOS and costs. RESULTS Overall, 5,834 hospital stays with CDI as the
      primary diagnosis were included in this study. The total national insurance costs
      were ?30.7 million (US $33,677,439), and the mean cost per hospital stay was
      ?5,267+/-?3,645 (US $5,777+/-$3,998). In total, 10,265 stays were reported with
      CDI as the secondary diagnosis. The total national insurance additional costs
      attributable to CDI were estimated to be ?85 million (US $93,243,725), and the
      mean additional cost attributable to CDI per hospital stay was ?8,295+/-?17,163,
      median, ?4,797 (US $9,099+/-$8,827; median, $5,262). CONCLUSION CDI has a high
      clinical and economic burden in the hospital, and it represents a major cost for
      national health insurance. When detected as a comorbidity, CDI was significantly
      associated with increased LOS and economic burden. Preventive approaches should
      be implemented to avoid CDIs. Infect Control Hosp Epidemiol 2017;38:906-911.

PMID- 28756806
TI  - ERK1/2-mediated Cytoplasmic Accumulation of hnRNPK Antagonizes TRAIL-induced
      Apoptosis through Upregulation of XIAP in H1299 Cells.
AB  - OBJECTIVE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      resistance greatly limits the clinical therapeutic efficacy of TRAIL. Elucidating
      the molecular mechanism underlying TRAIL resistance will be fundamental to
      resolving this problem. METHODS: Nuclear and cytoplasmic protein extraction and
      immuno?uorescence (IF) assay were used to detect changes in heterogeneous nuclear
      ribonucleoprotein K (hnRNPK) localization in H1299 cells. The evaluation of cell
      apoptosis in cells transfected with GFP-hnRNPK, GFP-hnRNPK S284/353A, or GFP
      hnRNPK S284/353D mutant was performed using cleaved caspase-3 antibody. The gene
      expression of XIAP was tested by quantitative RT-PCR. RESULTS: Previously, we
      reported that hnRNPK antagonized TRAIL-induced apoptosis through inhibition of
      PKC-mediated GSK3beta phosphorylation. In this study, we further demonstrate that
      TRAIL treatment induces cytoplasmic accumulation of hnRNPK in H1299 cells. The
      hnRNPK localized in the cytoplasm has a higher capacity to antagonize TRAIL
      induced apoptosis. Both ERK1/2 signaling inhibitor U0126 and ERK-phosphoacceptor
      site mutant (GFP-hnRNPK S284/353A) diminish cytoplasmic accumulation of hnRNPK
      induced by TRAIL. Moreover, we show that XIAP is involved in hnRNPK-mediated
      TRAIL resistance in H1299 cells. CONCLUSION: Taken together, these results give
      new insights into the understanding of the molecular mechanism associated with
      TRAIL resistance in lung adenocarcinoma.

PMID- 28756807
TI  - Association between Plasma Metal Levels and Diabetes Risk: a Case-control Study
      in China.
AB  - OBJECTIVE: Many metals, some of which have been classified as environmental
      endocrine disruptors, are used extensively in everyday consumer products and are
      ubiquitous in our living environment. In the present study, we aimed to explore
      the associations between the prevalence risk of type 2 diabetes and plasma levels
      of 20 trace elements as well as those of heavy metals in a Han Chinese
      population. METHODS: We conducted a case-control study to investigate the
      associations between plasma concentrations of 20 metals and diabetes in Jiangsu
      province. A total of 122 newly diagnosed cases of type 2 diabetes and 429 matched
      controls were recruited from community physical examinations in Suzhou City of
      Jiangsu Province. Plasma metal levels were measured by inductively-coupled plasma
      mass spectrometry. RESULTS: After adjusting for confounders, plasma vanadium,
      chromium, manganese, copper, zinc, arsenic, selenium, strontium, palladium,
      cadmium, cesium, and barium were associated with diabetes risk (P < 0.05). The
      adjusted OR increased with increasing concentration of vanadium, manganese,
      copper, zinc, and cesium. CONCLUSION: Many metals, including manganese, copper,
      zinc, arsenic, selenium, and cadmium in plasma, are associated with the morbidity
      of diabetes. Monitoring of environmental metal levels and further studies are
      urgently needed.

PMID- 28756808
TI  - Role of Immune Microenvironmental Factors for Improving the IPI-related Risk
      Stratification of Aggressive B Cell Lymphoma.
AB  - OBJECTIVE: To investigate the risk stratification of aggressive B cell lymphoma
      using the immune microenvironment and clinical factors. METHODS: A total of 127
      patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in
      this study. CD4, Foxp3, CD8, CD68, CD163, PD-1, and PD-L1 expression levels were
      evaluated in paraffin-embedded lymphoma tissues to identify their roles in the
      risk stratification. Eleven factors were identified for further evaluation using
      analysis of variance, chi-square, and multinomial logistic regression analysis.
      RESULTS: Significant differences in 11 factors (age, Ann Arbor stage, B symptom,
      ECOG performance status, infiltrating CD8+ T cells, PD-L1 expression, absolute
      blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and
      serum beta2-microglobulin) were observed among patient groups stratified by at
      least two risk stratification methods [International Prognostic Index (IPI),
      revised IPI, and NCCN-IPI models] (P < 0.05). Concordance rates were high (81.4%
      100.0%) when these factors were used for the risk stratification. No difference
      in the risk stratification results was observed with or without the Ann Arbor
      stage data. CONCLUSION: We developed a convenient and inexpensive tool for use in
      risk stratification of aggressive B cell lymphomas, although further studies on
      the role of immune microenvironmental factors are needed.

PMID- 28756809
TI  - First Report in China on the Identification and Drug Sensitivity of Mycobacterium
      elephantis Isolated from the Milk of a Cow with Mastitis.
AB  - OBJECTIVE: In this study, milk from a cow with mastitis was analyzed to determine
      the presence of mycobacterial infection. Milk quality and security problems
      pertaining to the safe consumption of dairy products were also discussed in this
      study. METHODS: Milk was preprocessed with 4% NaOH. Then, mycobacteria were
      isolated from the milk sample on L-J medium. The isolate was identified using
      multiple loci Polymerase Chain Reaction (PCR) and multi-locus sequence analysis
      with 16S rRNA, sodA, hsp65, and ITS genes. The drug sensitivity of the isolate to
      27 antibiotics was tested through alamar blue assay. RESULTS: Smooth, moist, pale
      yellow colonies appeared on the L-J medium within a week after inoculation. Based
      on the results of multiple loci PCR analysis, the isolate was preliminarily
      identified as non-tuberculous mycobacteria. The 16S rRNA, SodA, hsp65, and ITS
      gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities,
      respectively, with those of the published reference strains of Mycobacterium
      elephantis (M. elephantis). The drug sensitivity results showed that the strain
      is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive
      to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin,
      levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin,
      ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline. CONCLUSION:
      To the best of our knowledge, this study is initially to report the isolation of
      M. elephantis from the milk of a cow with mastitis in China.

PMID- 28756810
TI  - Serum Thyroglobulin-A Sensitive Biomarker of Iodine Nutrition Status and Affected
      by Thyroid Abnormalities and Disease in Adult Populations.
AB  - OBJECTIVE: To evaluate the usefulness of the thyroglobulin (Tg) level in adults
      as a nutritional biomarker of iodine status and to identify the factors related
      to the serum Tg level. METHODS: A cross-sectional study was conducted in adult
      populations of areas differing in iodine nutrition from three provinces
      (Autonomous Region) in China. Serum levels of thyroid hormones and Tg as well as
      thyroid autoantibodies were measured. The thyroid volume and nodule were measured
      by ultrasound. A multivariate linear regression analysis was used to assess
      iodine intake and other indeterminate factors associated with the serum Tg level.
      RESULTS: A total of 573 adults were recruited for this study. The serum Tg levels
      differed significantly among the three groups (22.27 MUg/L, 9.73 MUg/L and 15.77
      MUg/L in the excess, more-than-adequate, and deficient groups, respectively). The
      results of multivariate linear regression analysis indicate that excess and
      deficient iodine intake, goiter, thyroid nodule, hypothyroidism are significantly
      related with higher Tg level, and TgAb positivity is significantly related with
      lower serum Tg. CONCLUSION: The serum Tg level reflects abnormal thyroid function
      and is a sensitive functional biomarker of iodine nutrition status.

PMID- 28756811
TI  - Comparing the Genotype and Drug Susceptibilities between Mycobacterium avium and
      Mycobacterium intracellulare in China.
AB  - OBJECTIVE: Mycobacterium avium (M. avium) and Mycobacterium intracellulare (M.
      intracellulare) are the major causative agents of nontuberculous mycobacteria
      (NTM)-related pulmonary infections. However, little is known about the
      differences in drug susceptibility profiles between these two species. METHODS: A
      total of 393 NTM isolates were collected from Shanghai Pulmonary Disease
      Hospital. Sequencing of partial genes was performed to identify the strains at
      species level. The minimum inhibitory concentration (MIC) was used to evaluate
      the drug susceptibility against 20 antimicrobial agents. Variable number of
      tandem repeat (VNTR) typing was conducted to genotype these two species. RESULTS:
      A total of 173 (44.0%) M. avium complex (MAC) isolates were identified, including
      41 (10.4%) M. avium isolates and 132 (33.6%) M. intracellulare isolates.
      Clarithromycin and amikacin were the two most effective agents against MAC
      isolates. The Hunter-Gaston Discriminatory Index (HGDI) values for VNTR typing of
      M. avium and M. intracellulare isolates were 0.993 and 0.995, respectively.
      Levofloxacin resistance was more common among the unclustered strains than among
      the clustered strains of M. intracellulare. CONCLUSION: M. intracellulare was the
      most common NTM species in China. Clarithromycin and amikacin had high
      antimicrobial activities against MAC. VNTR typing of MAC isolates revealed a high
      discriminatory power. Levofloxacin resistance was associated with unclustered
      strains of M. intracellulare.

PMID- 28756812
TI  - Dog-transmitted Rabies in Beijing, China.
AB  - Rabies remains a continuous threat to public health in Beijing. In this study, a
      total of 224 brain tissues were collected from suspected infected stray dogs
      within Beijing between January 2015 and December 2016. Among them, total of 67
      samples were diagnosed positive for rabies. In the phylogenetic analysis, rabies
      in Beijing is currently a relatively independent public health issue originating
      from local rabid dogs apart from the imported cases from elsewhere in the
      country. Because vaccination of unregistered dogs against rabies is still
      neglected in Beijing and other regions of China, national and local authorities
      should play central roles in all related aspects, such as development of
      policies, engagement of stakeholders for public and professional education,
      entire vaccination process, and animal management.

PMID- 28756813
TI  - Heavy Metal Assessment among Chinese Nonferrous Metal-exposed Workers from the
      Jinchang Cohort Study.
AB  - Environmental exposure to heavy metals has been linked to a wide range of human
      health hazards. We detected the levels of 15 metals in urine samples from 500
      representative sub-samples in an ongoing occupational cohort study (Jinchang
      Cohort) to directly evaluate metal exposure levels. Fifteen metals, namely As,
      Ba, Be, Cd, Cs, Cr, Co, Cu, Pb, Mn, Ni, Se, Tl, U, and Zn, were detected by
      inductively coupled plasma quadruple mass spectrometry. The results showed that
      median creatinine adjustment and geometric mean urinary metal levels were higher
      in the heavy metal-exposed group, except Se and Zn, than other reported general
      or occupational populations. Further studies should address the effects of heavy
      metals on human health.

PMID- 28756814
TI  - Grape Seed Procyanidin Extract Reduces Arsenic-Induced Renal Inflammatory Injury
      in Male Mice.
AB  - The aim of the present study is to evaluate the ability and mechanism by which
      grape seed procyanidin extract (GSPE) relieves arsenic trioxide (As2O3)-induced
      renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3
      and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory
      cytokines of kidneys were examined by ELISA, whereas the expression levels of
      molecules involved in the nuclear factor (NF)-kappaB signaling pathway were
      evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE
      prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the
      NF-kappaB signaling pathway and inflammatory cytokine production, while promoting
      expression of anti-inflammatory cytokines.

PMID- 28756816
TI  - Epidemiological Characteristics and Risk Factors of the Pertussis in Infants < 12
      Months of Age in Tianjin, China.
AB  - The epidemiologic characteristics of 631 infant pertussis cases < 12 months,
      which accounted for 57.42% of the total cases, were analyzed by descriptive
      epidemiology in Tianjin, between 2010 and 2015. The incidence of infants was
      104.66/100,000, which was 118 times higher than in other age groups (P < 0.001).
      The primary type of pertussis simultaneously presented in households was adult-to
      infant (70.51%). The parents were identified as the source of infection in 80.18%
      of cases for infants. The positive rate of placental antibody transfer was 31.06%
      and 3.13% for 3-month-old infants. Infants presented the highest age-specific
      pertussis incidence. The most important reason was parents were the important
      sources of infection, and secondly the lower level of antibodies in neonates and
      the rapid waning of maternal antibody titer.

PMID- 28756815
TI  - Establishment of a Predictive Diagnostic Model for Acute Mycoplasma Pneumoniae
      Infection in Elderly Patients with Community-acquired Pneumonia.
AB  - We established a diagnostic model to predict acute Mycoplasma pneumoniae (M.
      pneumonia) infection in elderly Community-acquired pneumonia (CAP) patients. We
      divided 456 patients into acute and non-acute M. pneumoniae infection groups.
      Binary logistic regression and receiver operating characteristic (ROC) curves
      were used to establish a predictive model. The following independent factors were
      identified: age ? 70 years; serum cTNT level ? 0.05 ng/mL; lobar consolidation;
      mediastinal lymphadenopathy; and antibody titer in the acute phase ? 1:40. The
      area under the ROC curve of the model was 0.923 and a score of ? 7 score
      predicted acute M. pneumoniae infection in elderly patients with CAP. The
      predictive model developed in this study has high diagnostic accuracy for the
      identification of elderly acute M. pneumoniae infection.

PMID- 28756817
TI  - An integrated healthcare service for asylum seekers and refugees in the South
      Eastern Region of Melbourne: Monash Health Refugee Health and Wellbeing.
AB  - Asylum seekers and refugees generally have poorer health than the broader
      Australian population. However, these groups experience a range of barriers to
      accessing universal health services. Generalist and specialist refugee health
      services have been established in Australia to improve the health of humanitarian
      migrant groups. This article describes a refugee health service established in a
      high-settlement region of Melbourne, Australia, and explores clients' experiences
      with the service. Client feedback was captured through interviews (n=18) and
      surveys (n=159). Participants reported high levels of satisfaction with the
      service, and highlighted the value in having trusting relationships with staff,
      access to bicultural workers, onsite interpreting services and integrated care.
      The findings indicate that it is possible to engage asylum seekers and refugees
      through healthcare delivery that is responsive to the unique needs of this
      priority population.

PMID- 28756818
TI  - Erratum.

PMID- 28756819
TI  - Foreword.

PMID- 28756821
TI  - Acute care surgery: An evolving paradigm.

PMID- 28756822
TI  - Exposure to toxics during pregnancy and childhood and asthma in children: A pilot
      study.
AB  - Environmental factors, pesticides, alcohol and smoking are linked to asthma in
      children. The association of toxic substances exposure with asthma has not been
      evaluated. Our objective is to assess such associations among children aged less
      than 16years old. This is a cross-sectional study, conducted between January and
      May 2015, using a sample of Lebanese students from private schools in Beirut and
      Mount Lebanon. Out of 700 distributed questionnaires, 527 (75.2%) were returned
      to us. Verbal informed consent was also obtained from all parents prior to
      participating in the study. A significant association was found between waterpipe
      smoking and diagnosed asthma (p=0.003; ORa=13.25; 95% CI 2.472-71.026). Alcohol
      during pregnancy, waterpipe smoking during pregnancy and parents respiratory
      problems significantly increased the risk of respiratory problems by
      approximately 5 times, 6 times and 2 times respectively (p=0.016; ORa=4.889; 95%
      CI 1.339-17.844, p=0.021; ORa=6.083; 95% CI 1.314-28.172, p=0.004; ORa=1.748; 95%
      CI 1.197-2.554 respectively). Waterpipe smoking, alcohol during pregnancy,
      recurrent otitis and humidity at home seem to be significantly correlated with
      asthma in children. Spreading awareness by health care professionals is needed to
      permit a reduction of the prevalence of these allergic diseases, especially
      asthma, in children.

PMID- 28756823
TI  - Determination of carbapenem resistance mechanism in clinical isolates of
      Pseudomonas aeruginosa isolated from burn patients, in Tehran, Iran.
AB  - Carbapenems are the most important therapeutic options that effect against
      serious infections caused by multidrug resistant Pseudomonas aeruginosa (MDR-PA)
      isolates. Carbapenems resistant isolates of P. aeruginosa are increasing
      worldwide. The aim of this study was to determine the carbapenem resistance
      mechanisms in clinical P. aeruginosa isolates from burn patients, in Tehran,
      Iran. A total of 53 non-duplicated isolates of carbapenem-resistant P. aeruginosa
      were collected from burn patients. The presence of carbapenemase genes were
      determined by PCR. AmpC overproducer isolates were detected by phenotypic method.
      The mutation and transcription level of oprD were determined by PCR-sequencing
      and quantitative Real-time PCR (RT-PCR), respectively. Twenty-seven (50.9%)
      isolates were positive for carbapenemase (blaVIM=25 and blaIMP=2) and showed high
      level resistance to imipenem and meropenem. Twenty-eight isolates were AmpC
      overproducers. All isolates had a mutation in the oprD gene and down-regulation
      of oprD was found in 56.6% of MDR-PA isolates. Although the presence of
      carbapenemase is the common mechanism of resistant to carbapenem, but carbapenem
      resistance was found by oprD mutation-driven and the AmpC overproducing isolates
      in Tehran, Iran.

PMID- 28756824
TI  - Trends in lung cancer incidence in Lebanon by gender and histological type over
      the period 2005-2008.
AB  - INTRODUCTION: Lung cancer incidence rates, overall and by histologic subtypes,
      vary substantially by gender and smoking. This study's aim was to review data
      regarding trends in the number of cases of different lung-cancer histologies and
      relate these to smoking habits by gender in Lebanon. MATERIALS AND METHODS: Lung
      cancer data using ICD-O, 3rd edition, from the Lebanese National Cancer Registry
      from 2005 to 2008 were stratified by gender for histology type for patients aged
      over 18years. RESULTS: Lung cancer cases among males were 2.5 times higher than
      those in females. The most common lung cancer histology type for males and
      females was adenocarcinoma for all observed years. The proportion of squamous
      cell carcinoma in incident cases was significantly higher in males than in
      females for the total period from 2005 to 2008, P=0.032, but not in individual
      years. The ratio of adenocarcinoma to squamous cell carcinoma in incident cases
      between 2005 and 2008 was 2:45 for males and 3:15 for females. CONCLUSION: Lung
      cancer histology in Lebanon is following a pattern similar to that found in most
      countries of North America and in Europe, where adenocarcinoma is the most
      prevalent subtype among both males and females.

PMID- 28756825
TI  - The prevalence and association of stress with sleep quality among medical
      students.
AB  - INTRODUCTION: Medical students tend to reduce their sleep, in an effort to adjust
      and cope with their workload and stressful environment. This study estimated the
      prevalence of and the relationship between poor sleep quality and stress among
      medical students. METHODS: This cross-sectional study was conducted using a
      stratified random sample of male and female medical students in King Saud bin
      Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia. A self
      administered questionnaire was distributed to assess sleep quality using the
      Pittsburgh Sleep Quality Index, and the stress level by using the Kessler
      Psychological Distress Scale. RESULTS: A high prevalence of poor sleep quality
      (76%) and stress (53%) were found, with a statistically significant association
      (p<0.001). Logistic regression indicated that students who are not suffering from
      stress are less likely to have poor sleep quality (OR=0.28, p<0.001), and the
      risk of having poor sleep quality is almost four times higher in students whose
      cumulative grade point average (GPA) is less than 4.25 (OR=3.83, p=0.01).
      CONCLUSION: The study documents a statistically significant association between
      stress and poor sleep quality. A recommendation for the management of medical
      college is to establish academic counseling centers focusing in promoting good
      sleep hygiene and strengthening students' study skills and coping with their
      stressful environment.

PMID- 28756826
TI  - Frequency of multi-drug resistance and mutations in Mycobacterium tuberculosis
      isolates from Punjab state of India.
AB  - Data regarding prevalence of multi-drug resistant tuberculosis (MDR-TB) and
      associated common mutations is scarce from Punjab region. The study was designed
      to determine rate of MDR-TB among presumptive MDR-TB from Punjab and mutation
      patterns using GenoType MTBDRplus assay. Total of 812 consecutive sputum samples
      were received from January 2012 to July 2013, from 14 districts of Punjab at the
      National Reference Laboratory at New Delhi for diagnosis of MDR-TB as hand
      holding activity. Presumptive MDR-TB patients were identified on basis of
      criterion B defined by the programme. Smear positive and negatives patients were
      found to be 636/798 (79.7%) and 162/ 798 (20.3%) respectively. Total of 606
      GenoType MTBDRplus tests were conducted and mutations in rpoB, kat G and inhA
      genes analyzed. Total of 94/606 (15.5%), 43/606 (7.1%) and 40/606 (6.6%) were
      found to be RIF and INH resistant, mono-RIF resistant and 40/606 (6.6%) mono-INH
      resistant respectively. Commonest known mutation for RIF in rpoB gene and INH in
      kat G gene was S531L (80/ 137; 58.4%) and S315T1 (119/134; 88.8%) respectively.
      Mutations in inhA were found in 21/134 (15.7%) strains. Average turn-around time
      (TAT) for dispatch of result toPunjab was 4.6days. Prevalence of RIF resistance
      in Punjab was found to be 22.6%. Common mutations for RIF and INH were similar to
      that in other regions of country. GenoType MTBDRplus was found to be useful assay
      for rapid detection of MDR-TB, responsible for determining better management of
      MDR-TB patients under the programme.

PMID- 28756827
TI  - Ground water as the source of an outbreak of Salmonella Enteritidis.
AB  - In September 2014, an outbreak of gastroenteritis was reported to the Public
      Health Institute of Sibenik and Knin County in Croatia. The outbreak occurred in
      the County center of Sibenik, a town with 50,000 inhabitants, and it lasted for
      12days. An epidemiological investigation suggested a nearby water spring as the
      source of the outbreak. Due to the temporary closure of the public water supply
      system, the inhabitants started to use untreated water from a nearby spring.
      Microbiological analysis revealed that the outbreak was caused by Salmonella
      enterica subsp. enterica serovar Enteritidis that was isolated from stool samples
      of the patients and ground water. The isolates were further analysed with pulsed
      field gel electrophoresis using XbaI, which revealed an identical
      macrorestriction profile. Although 68 cases were reported, it was estimated that
      the actual number of affected persons was more than several hundred. In order to
      prevent further spread of disease, public advice was released immediately after
      the first epidemiological indication and a warning sign was placed at the
      incriminated water source, after microbiological confirmation. It is necessary to
      regularly monitor microbiological quality of ground water especially in urban
      areas and provide adequate education and awareness to the inhabitants regarding
      the risk of using untreated ground water.

PMID- 28756828
TI  - Is Google Trends a reliable tool for digital epidemiology? Insights from
      different clinical settings.
AB  - Internet-derived information has been recently recognized as a valuable tool for
      epidemiological investigation. Google Trends, a Google Inc. portal, generates
      data on geographical and temporal patterns according to specified keywords. The
      aim of this study was to compare the reliability of Google Trends in different
      clinical settings, for both common diseases with lower media coverage, and for
      less common diseases attracting major media coverage. We carried out a search in
      Google Trends using the keywords "renal colic", "epistaxis", and "mushroom
      poisoning", selected on the basis of available and reliable epidemiological data.
      Besides this search, we carried out a second search for three clinical conditions
      (i.e., "meningitis", "Legionella Pneumophila pneumonia", and "Ebola fever"),
      which recently received major focus by the Italian media. In our analysis, no
      correlation was found between data captured from Google Trends and epidemiology
      of renal colics, epistaxis and mushroom poisoning. Only when searching for the
      term "mushroom" alone the Google Trends search generated a seasonal pattern which
      almost overlaps with the epidemiological profile, but this was probably mostly
      due to searches for harvesting and cooking rather than to for poisoning. The
      Google Trends data also failed to reflect the geographical and temporary patterns
      of disease for meningitis, Legionella Pneumophila pneumonia and Ebola fever. The
      results of our study confirm that Google Trends has modest reliability for
      defining the epidemiology of relatively common diseases with minor media
      coverage, or relatively rare diseases with higher audience. Overall, Google
      Trends seems to be more influenced by the media clamor than by true
      epidemiological burden.

PMID- 28756829
TI  - Occupational stress, anxiety and depression among Egyptian teachers.
AB  - Occupational stress (OS) among teachers predispose to depression and anxiety. No
      study was done to assess these problems among Egyptian teachers. This study aimed
      to assess the prevalence of OS, depression and anxiety among Egyptian teachers. A
      cross sectional study was done on 568 Egyptian teachers. The respondents filled a
      questionnaire on personal data, and the Arabic version of the Occupational Stress
      Index (OSI), the Arabic validated versions of Taylor manifest anxiety scale and
      the Beck Depression Inventory (BDI) were used to assess OS, anxiety and
      depression respectively. The prevalence of OS, anxiety and depression among
      teachers was (100%, 67.5% and 23.2%) respectively. OS, anxiety and depression
      scores were significantly higher among teachers with an age more than 40years,
      female teachers, primary school teachers, those with inadequate salary, higher
      teaching experience, higher qualifications and higher workload. A significant
      weak positive correlation was found between OS scores and anxiety and depression
      scores. This study indicated the need for future researches to address risk
      factors of OS and mental disorders among Egyptian teachers, and the need of
      periodical medical evaluation of teachers and medical and psychological support
      for the identified cases.

PMID- 28756830
TI  - Predictors of past quit attempts and duration of abstinence among cigarette
      smokers.
AB  - OBJECTIVE: Despite the widespread awareness of the harms of smoking, millions
      continue to smoke around the world partly due to the difficulty it takes to quit
      smoking. Identifying the factors associated with making quit attempts is an
      essential pillar to reach successful quitting. The purpose of this study is to
      assess the factors associated with the past quit attempts and their past length
      of abstinence in a Lebanese sample of cigarette smokers. METHODS: This study was
      conducted between March 2014 and March 2015, involving 382 patients randomly
      chosen from 5 outpatient clinics in 5 hospitals in Lebanon. A standardized
      questionnaire was completed including socio-demographic characteristics, smoking
      behavior, chronic respiratory symptoms, Fagerstrom scale, Mondor scale, packaging
      perception, quitting behavior and readiness to quit ladder. RESULTS: Smokers who
      have chronic allergies (ORa=2.45, p=0.03), those who have ever stopped smoking
      for at least one month due to the warnings implemented on the packages (ORa=4.6,
      p<0.0001) and smokers with an intention to quit in 2months (ORa=2.49, p<0.0001)
      had significantly more past quit attempts. Furthermore, longer quit attempts
      duration (more than 1month) were significantly associated with low-nicotine
      dependent smokers (ORa=0.56, p=0.02), higher-motivated smokers (ORa=1.85,
      p=0.01), people with chronic allergies (ORa=2.07, p=0.02), smokers who have ever
      stopped smoking for at least one month due to the warnings (ORa=3.72, p<0.0001)
      and those with an intention to quit in 2months (ORa=1.98, p=0.05). CONCLUSION:
      The promoters of smoking cessation services should consider these factors when
      designing comprehensive tobacco control initiatives and in service planning.

PMID- 28756831
TI  - Frequency and implications of ofloxacin resistance among previously treated
      tuberculosis patients.

PMID- 28756832
TI  - Erratum in: "Erratum to Recurrence of gallstone disease following non-surgical
      treatment of acute cholecystitis in the elderly population" [Med Clin (Barc).
      (2017) 149(3)-139].

PMID- 28756833
TI  - Corrigendum to: Biocompatibility evaluation of a thermoplastic rubber for
      wireless telemetric intracranial pressure sensor coating.

PMID- 28756834
TI  - Oxidative Degradation of Polysorbate Surfactants Studied by Liquid Chromatography
      Mass Spectrometry.
AB  - Polysorbates (PSs), as acquired from manufacturing processes and chemical nature
      of fatty acids (FAs) used in production of biotherapeutic formulations, are
      heterogeneous mixtures of structurally related compounds, covering a wide range
      of physicochemical properties. Such complexity presents a certain challenge for
      analysis of these important surfactants and demands the use of methods offering
      sufficient resolution to monitor individual classes of species and detect changes
      upon stress. A liquid chromatography mass spectrometry method, benefiting from
      the use of low m/z marker ions, simplifies profiling of PSs by providing detailed
      information on FA composition even of chromatographically overlapping peaks. The
      ability of the method to monitor individual components and follow their changes
      because of oxidative stress was explored. A water-soluble azo compound was used
      as a model oxidizer. Major degradation products of PS 80, because of reactions
      involving double bond, were identified as oxo-C9:0, keto-C18:1, hydroxyl-C18:1,
      epoxy-C18:0, and hydroperoxy-C18:1. Stability of PS 20 components was found to
      depend on the carbon number of polyethoxylated (POE) sorbitan FA ester and its
      order. Rates of oxidative degradation increased with the length of the FA ester
      and, moreover, POE sorbitan diesters degraded significantly faster in comparison
      to the corresponding monoesters upon the oxidative stress. (c) 2015 Wiley
      Periodicals, Inc. and the American Pharmacists Association.

PMID- 28756835
TI  - Systematic Screening of Different Surface Modifiers for the Production of
      Physically Stable Nanosuspensions.
AB  - The role of a surface modifier is important in the formation of stable
      nanosuspensions. In this study, a simple and systematic screening method for
      selecting optimum surface modifiers was performed by utilizing a low-energy wet
      ball milling method. Nine surface modifiers from different classes with different
      stabilization mechanisms were applied on six different models of active
      pharmaceutical ingredients (API). Particle size analysis showed that at
      concentration five times higher than the critical micelle concentration, SDS and
      sodium cholate (anionic surfactant) showed the highest percent success to produce
      stable nanosuspensions with particle size smaller than 250nm. Similar findings
      were also shown by poloxamer 188 (nonionic surfactant) and
      hydroxypropylmethylcellulose E5 (polymeric stabilizer) at concentration 1% (w/v)
      and 0.8% (w/v), respectively. In addition, combinations of anionic surfactant and
      nonionic surfactant as well as combinations of anionic surfactant and polymeric
      stabilizer showed high percent success in the formation of stable
      nanosuspensions. In general, no correlation can be found between the
      physicochemical characteristics of the model API (molecular weight, melting
      point, log P, pKa, and crystallinity) with its feasibility to be nanosized. The
      concentration and the principle of stabilization of surface modifier determine
      the formation of stable nanosuspensions. (c) 2015 Wiley Periodicals, Inc. and the
      American Pharmacists Association.

PMID- 28756836
TI  - Editorial.

PMID- 28756837
TI  - Editorial.

PMID- 28756838
TI  - Editorial.

PMID- 28756839
TI  - Achieving Continuous Manufacturing May 20-21 2014 Continuous Manufacturing
      Symposium.

PMID- 28756840
TI  - Achieving Continuous Manufacturing: Technologies and Approaches for Synthesis,
      Workup, and Isolation of Drug Substance May 20-21, 2014 Continuous Manufacturing
      Symposium.
AB  - This whitepaper highlights current challenges and opportunities associated with
      continuous synthesis, workup, and crystallization of active pharmaceutical
      ingredients (drug substances). We describe the technologies and requirements at
      each stage and emphasize the different considerations for developing continuous
      processes compared with batch. In addition to the specific sequence of operations
      required to deliver the necessary chemical and physical transformations for
      continuous drug substance manufacture, consideration is also given to how
      adoption of continuous technologies may impact different manufacturing stages in
      development from discovery, process development, through scale-up and into full
      scale production. The impact of continuous manufacture on drug substance quality
      and the associated challenges for control and for process safety are also
      emphasized. In addition to the technology and operational considerations
      necessary for the adoption of continuous manufacturing (CM), this whitepaper also
      addresses the cultural, as well as skills and training, challenges that will need
      to be met by support from organizations in order to accommodate the new work
      flows. Specific action items for industry leaders are.

PMID- 28756841
TI  - Achieving Continuous Manufacturing for Final Dosage Formation: Challenges and How
      to Meet Them May 20-21 2014 Continuous Manufacturing Symposium.
AB  - We describe the key issues and possibilities for continuous final dosage
      formation, otherwise known as downstream processing or drug product
      manufacturing. A distinction is made between heterogeneous processing and
      homogeneous processing, the latter of which is expected to add more value to
      continuous manufacturing. We also give the key motivations for moving to
      continuous manufacturing, some of the exciting new technologies, and the barriers
      to implementation of continuous manufacturing. Continuous processing of
      heterogeneous blends is the natural first step in converting existing batch
      processes to continuous. In heterogeneous processing, there are discrete
      particles that can segregate, versus in homogeneous processing, components are
      blended and homogenized such that they do not segregate. Heterogeneous processing
      can incorporate technologies that are closer to existing technologies, where
      homogeneous processing necessitates the development and incorporation of new
      technologies. Homogeneous processing has the greatest potential for reaping the
      full rewards of continuous manufacturing, but it takes long-term vision and a
      more significant change in process development than heterogeneous processing.
      Heterogeneous processing has the detriment that, as the technologies are adopted
      rather than developed, there is a strong tendency to incorporate correction
      steps, what we call below "The Rube Goldberg Problem." Thus, although
      heterogeneous processing will likely play a major role in the near-term
      transformation of heterogeneous to continuous processing, it is expected that
      homogeneous processing is the next step that will follow. Specific action items
      for industry leaders are.

PMID- 28756842
TI  - Regulatory and Quality Considerations for Continuous Manufacturing May 20-21,
      2014 Continuous Manufacturing Symposium.
AB  - This paper assesses the current regulatory environment, relevant regulations and
      guidelines, and their impact on continuous manufacturing. It summarizes current
      regulatory experience and learning from both review and inspection perspectives.
      It outlines key regulatory aspects, including continuous manufacturing process
      description and control strategy in regulatory files, process validation, and key
      Good Manufacturing Practice (GMP) requirements. In addition, the paper identifies
      regulatory gaps and challenges and proposes a way forward to facilitate
      implementation. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists
      Association.

PMID- 28756843
TI  - White Paper on Continuous Bioprocessing May 20-21 2014 Continuous Manufacturing
      Symposium.
AB  - There is a growing interest in realizing the benefits of continuous processing in
      biologics manufacturing, which is reflected by the significant number of
      industrial and academic researchers who are actively involved in the development
      of continuous bioprocessing systems. These efforts are further encouraged by
      guidance expressed in recent US FDA conference presentations. The advantages of
      continuous manufacturing include sustained operation with consistent product
      quality, reduced equipment size, high-volumetric productivity, streamlined
      process flow, low-process cycle times, and reduced capital and operating cost.
      This technology, however, poses challenges, which need to be addressed before
      routine implementation is considered. This paper, which is based on the available
      literature and input from a large number of reviewers, is intended to provide a
      consensus of the opportunities, technical needs, and strategic directions for
      continuous bioprocessing. The discussion is supported by several examples
      illustrating various architectures of continuous bioprocessing systems. (c) 2014
      Wiley Periodicals, Inc. and the American Pharmacists Association.

PMID- 28756844
TI  - Equipment and Analytical Companies Meeting Continuous Challenges May 20-21 2014
      Continuous Manufacturing Symposium.
AB  - This white paper focuses on equipment, and analytical manufacturers'
      perspectives, regarding the challenges of continuous pharmaceutical manufacturing
      across five prompt questions. In addition to valued input from several vendors,
      commentary was provided from experienced pharmaceutical representatives, who have
      installed various continuous platforms. Additionally, a small medium enterprise
      (SME) perspective was obtained through interviews. A range of technical
      challenges is outlined, including: the presence of particles, equipment
      scalability, fouling (and cleaning), technology derisking, specific analytical
      challenges, and the general requirement of improved technical training. Equipment
      and analytical companies can make a significant contribution to help the
      introduction of continuous technology. A key point is that many of these
      challenges exist in batch processing and are not specific to continuous
      processing. Backward compatibility of software is not a continuous issue per se.
      In many cases, there is available learning from other industries. Business models
      and opportunities through outsourced development partners are also highlighted.
      Agile smaller companies and academic groups have a key role to play in developing
      skills, working collaboratively in partnerships, and focusing on solving relevant
      industry challenges. The precompetitive space differs for vendor companies
      compared with large pharmaceuticals. Currently, there is no strong consensus
      around a dominant continuous design, partly because of business dynamics and
      commercial interests. A more structured common approach to process design and
      hardware and software standardization would be beneficial, with initial practical
      steps in modeling. Conclusions include a digestible systems approach, accessible
      and published business cases, and increased user, academic, and supplier
      collaboration. This mirrors US FDA direction. The concept of silos in
      pharmaceutical companies is a common theme throughout the white papers. In the
      equipment domain, this is equally prevalent among a broad range of companies,
      mainly focusing on discrete areas. As an example, the flow chemistry and
      secondary drug product communities are almost entirely disconnected. Control and
      Process Analytical Technologies (PAT) companies are active in both domains. The
      equipment actors are a very diverse group with a few major Original Equipment
      Manufacturers (OEM) players and a variety of SME, project providers, integrators,
      upstream downstream providers, and specialist PAT. In some cases, partnerships or
      alliances are formed to increase critical mass. This white paper has focused on
      small molecules; equipment associated with biopharmaceuticals is covered in a
      separate white paper. More specifics on equipment detail are provided in final
      dosage form and drug substance white papers. The equipment and analytical
      development from laboratory to pilot to production is important, with a variety
      of sensors and complexity reducing with scale. The importance of robust
      processing rather than overcomplex control strategy mitigation is important. A
      search of nonacademic literature highlights, with a few notable exceptions, a
      relative paucity of material. Much focuses on the economics and benefits of
      continuous, rather than specifics of equipment issues. The disruptive nature of
      continuous manufacturing represents either an opportunity or a threat for many
      companies, so the incentive to change equipment varies. Also, for many companies,
      the pharmaceutical sector is not actually the dominant sector in terms of sales.
      (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

PMID- 28756845
TI  - Control Systems Engineering in Continuous Pharmaceutical Manufacturing May 20-21,
      2014 Continuous Manufacturing Symposium.
AB  - This white paper provides a perspective of the challenges, research needs, and
      future directions for control systems engineering in continuous pharmaceutical
      processing. The main motivation for writing this paper is to facilitate the
      development and deployment of control systems technologies so as to ensure
      quality of the drug product. Although the main focus is on small-molecule
      pharmaceutical products, most of the same statements apply to biological drug
      products. An introduction to continuous manufacturing and control systems is
      followed by a discussion of the current status and technical needs in process
      monitoring and control, systems integration, and risk analysis. Some key points
      are that: (1) the desired objective in continuous manufacturing should be the
      satisfaction of all critical quality attributes (CQAs), not for all variables to
      operate at steady-state values; (2) the design of start-up and shutdown
      procedures can significantly affect the economic operation of a continuous
      manufacturing process; (3) the traceability of material as it moves through the
      manufacturing facility is an important consideration that can at least in part be
      addressed using residence time distributions; and (4) the control systems
      technologies must assure quality in the presence of disturbances, dynamics,
      uncertainties, nonlinearities, and constraints. Direct measurement, first
      principles and empirical model-based predictions, and design space approaches are
      described for ensuring that CQA specifications are met. Ways are discussed for
      universities, regulatory bodies, and industry to facilitate working around or
      through barriers to the development of control systems engineering technologies
      for continuous drug manufacturing. Industry and regulatory bodies should work
      with federal agencies to create federal funding mechanisms to attract faculty to
      this area. Universities should hire faculty interested in developing first
      principles models and control systems technologies for drug manufacturing that
      are easily transportable to industry. Industry can facilitate the move to
      continuous manufacturing by working with universities on the conception of new
      continuous pharmaceutical manufacturing process unit operations that have the
      potential to make major improvements in product quality, controllability, or
      reduced capital and/or operating costs. Regulatory bodies should ensure that: (1)
      regulations and regulatory practices promote, and do not derail, the development
      and implementation of continuous manufacturing and control systems engineering
      approaches; (2) the individuals who approve specific regulatory filings are
      sufficiently trained to make good decisions regarding control systems approaches;
      (3) provide regulatory clarity and eliminate/reduce regulatory risks; (4)
      financially support the development of high-quality training materials for use of
      undergraduate students, graduate students, industrial employees, and regulatory
      staff; (5) enhance the training of their own technical staff by financially
      supporting joint research projects with universities in the development of
      continuous pharmaceutical manufacturing processes and the associated control
      systems engineering theory, numerical algorithms, and software; and (6) strongly
      encourage the federal agencies that support research to fund these research
      areas. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

PMID- 28756846
TI  - Future Supply Chains Enabled by Continuous Processing-Opportunities Challenges
      May 20-21 2014 Continuous Manufacturing Symposium.
AB  - This paper examines the opportunities and challenges facing the pharmaceutical
      industry in moving to a primarily "continuous processing"-based supply chain. The
      current predominantly "large batch" and centralized manufacturing system designed
      for the "blockbuster" drug has driven a slow-paced, inventory heavy operating
      model that is increasingly regarded as inflexible and unsustainable. Indeed, new
      markets and the rapidly evolving technology landscape will drive more product
      variety, shorter product life-cycles, and smaller drug volumes, which will
      exacerbate an already unsustainable economic model. Future supply chains will be
      required to enhance affordability and availability for patients and healthcare
      providers alike despite the increased product complexity. In this more
      challenging supply scenario, we examine the potential for a more pull driven,
      near real-time demand-based supply chain, utilizing continuous processing where
      appropriate as a key element of a more "flow-through" operating model. In this
      discussion paper on future supply chain models underpinned by developments in the
      continuous manufacture of pharmaceuticals, we have set out; The paper recognizes
      that although current batch operational performance in pharma is far from optimal
      and not necessarily an appropriate end-state benchmark for batch technology, the
      adoption of continuous supply chain operating models underpinned by continuous
      production processing, as full or hybrid solutions in selected product supply
      chains, can support industry transformations to deliver right-first-time quality
      at substantially lower inventory profiles. (c) 2015 The Authors. Journal of
      Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American
      Pharmacists Association.

PMID- 28756847
TI  - How Development and Manufacturing Will Need to Be Structured-Heads of
      Development/Manufacturing May 20-21, 2014 Continuous Manufacturing Symposium.
AB  - Continuous manufacturing (CM) is a process technology that has been used in the
      chemical industry for large-scale mass production of chemicals in single-purpose
      plants with benefit for many years. Recent interest has been raised to expand CM
      into the low-volume, high-value pharmaceutical business with its unique
      requirements regarding readiness for human use and the required quality, supply
      chain, and liability constraints in this business context. Using a fairly
      abstract set of definitions, this paper derives technical consequences of CM in
      different scenarios along the development-launch-supply axis in different
      business models and how they compare to batch processes. Impact of CM on
      functions in development is discussed and several operational models suitable for
      originators and other business models are discussed and specific aspects of CM
      are deduced from CM's technical characteristics. Organizational structures of
      current operations typically can support CM implementations with just minor
      refinements if the CM technology is limited to single steps or small sequences
      (bin-to-bin approach) and if the appropriate technical skill set is available. In
      such cases, a small, dedicated group focused on CM is recommended. The
      manufacturing strategy, as centralized versus decentralized in light of CM
      processes, is discussed and the potential impact of significantly shortened
      supply lead times on the organization that runs these processes. The ultimate CM
      implementation may be seen by some as a totally integrated monolithic plant, one
      that unifies chemistry and pharmaceutical operations into one plant. The
      organization supporting this approach will have to reflect this change in scope
      and responsibility. The other extreme, admittedly futuristic at this point, would
      be a highly decentralized approach with multiple smaller hubs; this would require
      a new and different organizational structure. This processing approach would open
      up new opportunities for products that, because of stability constraints or
      individualization to patients, do not allow centralized manufacturing approaches
      at all. Again, the entire enterprise needs to be restructured accordingly. The
      situation of CM in an outsourced operation business model is discussed. Next
      steps for the industry are recommended. In summary, opportunistic implementation
      of isolated steps in existing portfolios can be implemented with minimal
      organizational changes; the availability of the appropriate skills is the
      determining factor. The implementation of more substantial sequences requires
      business processes that consider the portfolio, not just single products.
      Exploration and implementation of complete process chains with consequences for
      quality decisions do require appropriate organizational support. (c) 2015 Wiley
      Periodicals, Inc. and the American Pharmacists Association.

PMID- 28756848
TI  - Using Improved Serial Blood Sampling Method of Mice to Study Pharmacokinetics and
      Drug-Drug Interaction.
AB  - In pharmacokinetic evaluation of mice, using serial sampling methods rather than
      a terminal blood sampling method could reduce the number of animals needed and
      lead to more reliable data by excluding individual differences. In addition,
      using serial sampling methods can be valuable for evaluation of the drug-drug
      interaction (DDI) potential of drug candidates. In this study, we established an
      improved method for serially sampling the blood from one mouse by only one
      incision of the lateral tail vein, and investigated whether our method could be
      adapted to pharmacokinetic and DDI studies. After intravenous and oral
      administration of ibuprofen and fexofenadine (BCS class II and III), the plasma
      concentration and pharmacokinetic parameters were evaluated by our method and a
      terminal blood sampling method, with the result that both methods gave comparable
      results (ibuprofen: 63.8+/-4.0% and 64.4%, fexofenadine: 6.5+/-0.7% and 7.9%,
      respectively, in bioavailability). In addition, our method could be adapted to
      DDI study for cytochrome P450 and organic anion transporting polypeptide
      inhibition. These results demonstrate that our method can be useful for
      pharmacokinetic evaluation from the perspective of reliable data acquisition as
      well as easy handling and low stress to mice and improve the quality of
      pharmacokinetic and DDI studies.

PMID- 28756849
TI  - Tetrakis(p-Carboranylthio-Tetrafluorophenyl)Chlorin (TPFC): Application for
      Photodynamic Therapy and Boron Neutron Capture Therapy.
AB  - Carboranyl-containing chlorins have emerged as promising dual sensitizers for use
      in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by
      virtue of their known tumor affinity, low cytotoxicity in dark conditions, and
      their strong absorptions in the red region of the optical spectrum. Tetrakis(p
      carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl
      containing chlorin of high boron content (24% by weight). To evaluate TPFC's
      applicability as sensitizer for both PDT and BNCT, we performed an in vitro and
      in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor
      models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is
      currently used in clinical BNCT studies, via intravenous administration (i.v.)
      and/or used TPFC via convection-enhanced delivery (CED), a method for local drug
      infusion directly into the brain. In the in vitro PDT study, the cell surviving
      fraction following laser irradiation (9J/cm2) was 0.035 whereas in the in vitro
      BNCT study, the cell surviving fraction following neutron irradiation (thermal
      neutron=1.73*1012 n/cm2) was 0.04. In the in vivo BNCT study, the median survival
      time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42days
      (95% confidence interval; 37-43days). (c) 2014 Wiley Periodicals, Inc. and the
      American Pharmacists Association.

PMID- 28756850
TI  - Biomarker responses of Cu-induced toxicity in European seabass Dicentrarchus
      labrax: Assessing oxidative stress and histopathological alterations.
AB  - A comprehensive approach to chemical accumulation and biological effects of short
      term Cu exposure in juveniles of European seabass (Dicentrarchus labrax) has been
      achieved. Fish were exposed to 0.01-10mgL-1 nominal Cu concentrations for 24-96h.
      Metal concentrations in water and gills, liver, muscle and brain tissues were
      studied along with oxidative stress biomarkers (superoxide dismutase, catalase,
      glutathione peroxidase, lipid peroxidation). Induction of oxidative damage was
      observed in all the organs with differential antioxidant responses; gills
      appearing as the most sensitive from low environmentally water Cu concentrations
      as 0.01mgL-1. Histopathological alterations were also observed in liver and
      gills, even without a significant Cu accumulation. The results show that the
      combination of oxidative stress parameters, particularly lipid peroxidation and
      glutathione peroxidase activities, and histopathological alterations provide a
      good model fish and reliable early biomarkers for monitoring Cu pollution in
      seawater and might call for the protection agencies to revise the Cu
      environmental standards.

PMID- 28756851
TI  - Guidelines for coordinated radiologist/gynecologist-obstetrician management of
      patients requiring fetal MRI or CT.

PMID- 28756852
TI  - The McDonaldization of appraisal? Doctors' views of the early impacts of medical
      revalidation in the United Kingdom.
AB  - INTRODUCTION: Medical regulation is rapidly changing with claims that systems
      such as revalidation/relicensing will reassure the public. Yet the impact of such
      initiatives is unknown. METHODS: Using the principles of efficiency,
      calculability, predictability and control through technology, identified by
      Ritzer, and exampled by the McDonalds business model, we analyzed interviews with
      doctors between May 2012-Dec 2013 which focused on doctor experiences of
      appraisal and revalidation in SW England. RESULTS: The research found significant
      changes in appraisals since the launch of revalidation in December 2012.
      Appraisal has been standardized with a list of supporting information that must
      be collected by doctors. The success of implementation is measured in the numbers
      of appraisals completed but less is known about the quality of the appraisal
      itself. Such efficiencies have been supported by IT systems that themselves might
      be at risk of driving the process. DISCUSSION: There are potential advantages to
      McDonaldization including appraisals available to all, not just for doctors
      working in the NHS, and a potentially more appetizing recipe for their
      completion. As yet a state of McAppraisal has not been reached; with a complete
      transfer of trust in the doctor to trust in the appraisal process within
      revalidation. However policymakers will need to continue to ensure that
      regulatory initiatives, such as revalidation, are not just a process for their
      own sake.

PMID- 28756853
TI  - Functional patterned coatings by thin polymer film dewetting.
AB  - An approach for the fabrication of functional polymer surface coatings is
      introduced, where micro-scale structure and surface functionality are obtained by
      means of self-assembly mechanisms. We illustrate two main applications of micro
      patterned polymer surfaces obtained through dewetting of bilayers of thin polymer
      films. By tuning the physical and chemical properties of the polymer bilayers,
      micro-patterned surface coatings could be produced that have applications both
      for the selective attachment and patterning of proteins and cells, with potential
      applications as biomaterials, and for the collection of water from the
      atmosphere. In all cases, the aim is to achieve functional coatings using
      approaches that are simple to realize, use low cost materials and are potentially
      scalable.

PMID- 28756854
TI  - Three-dimensional carbon architectures for electrochemical capacitors.
AB  - Three-dimensional (3D) carbon-based materials are emerging as promising electrode
      candidates for energy storage devices. In comparison to the 1D and 2D structures,
      3D morphology offers new opportunities in rational design and synthesis of novel
      architectures tailor-made for promoting electrochemical performance. The
      capability of building hierarchical porous structures with 3D configuration can
      significantly advance the performance of energy storage devices by simultaneously
      enhancing the ion-accessible surface area and ion diffusion. This feature article
      presents an overview of recent progress in design, synthesis and implementation
      of 3D carbon-based materials as electrodes for electrochemical capacitors.
      Synthesis methodologies of four types of 3D carbon-based electrodes: 3D
      exfoliated carbon structures, 3D graphene scaffolds, 3D hierarchical porous
      carbon foams, as well as 3D architectures with periodic pores derived from direct
      ink writing, are thoroughly discussed and highlighted with selected experimental
      works. Finally, key opportunities and challenges in which different 3D carbons
      can significantly impact the energy storage and conversion communities will be
      provided.

PMID- 28756855
TI  - Interaction of "Candidatus Accumulibacter" and nitrifying bacteria to achieve
      energy-efficient denitrifying phosphorus removal via nitrite pathway from sewage.
AB  - To achieve energy-efficient denitrifying phosphorus removal via nitrite pathway
      from sewage, interaction of "Candidatus Accumulibacter" and nitrifying bacteria
      was investigated in a continuous-flow process. When nitrite in returned sludge of
      secondary settler was above 13mg/L, nitrite inhibition on anaerobic P-release of
      poly-phosphate organisms (PAOs) occurred. Clades IIC and IID were dominant,
      reaching 3.1%-11.9% of total bacteria. Clade IIC was sensitive to nitrite. Under
      low concentration of nitrite (<8mg/L), clade IIC primarily contributed to anoxic
      P-uptake. Clade IID had a strong tolerance to nitrite exposure. At high nitrite
      level (above 16mg/L), anoxic P-uptake was mainly performed by clade IID due to
      its strong tolerance to nitrite exposure. Ammonia oxidizing bacteria (AOB),
      nitrite oxidizing bacteria (NOB) and Accumulibacter interacted through variations
      of nitrite accumulation. High AOB abundance coupled with inhibition of NOB
      favored denitrifying phosphorus removal by clade IID. All Accumulibacter lineages
      were sorted into four clades of Type II. The most dominant ppk1 gene homologs
      were affiliated with clade IID, accounting for 69% of ppk1 clone library, and
      thus played an important role in denitrifying phosphorus removal via nitrite
      pathway.

PMID- 28756856
TI  - Production of d-psicose from d-glucose by co-expression of d-psicose 3-epimerase
      and xylose isomerase.
AB  - d-Psicose has been drawing increasing attention in recent years because of its
      medical and health applications. The production of d-psicose from d-glucose
      requires the co-expression and synergistic action of xylose isomerase and d
      psicose 3-epimerase. To co-express these genes, vector pET-28a(+)-dual containing
      two T7 promoters and RBS sites and an Multiple Cloning Sites was constructed
      using the Escherichia coli expression plasmid pET-28a(+). The xylose isomerase
      gene from E. coli MG1665 and the d-psicose 3-epimerase gene from Agrobacterium
      tumefaciens CGMCC 1.1488 were cloned and co-expressed in E. coli BL21(DE3). After
      24h incubation with the dual enzyme system at 40 degrees C, the sugar conversion
      ratio from d-glucose to d-psicose reached 10%. The optimal conditions were 50
      degrees C, pH 7.5 with Co2+ and Mg2+. The d-psicose yields from sugarcane bagasse
      and microalgae hydrolysate were 1.42 and 1.69g/L, respectively.

PMID- 28756857
TI  - Preparation of glutaraldehyde-treated lipase-inorganic hybrid nanoflowers and
      their catalytic performance as immobilized enzymes.
AB  - The use of protein-inorganic hybrid nanoflowers for the immobilization of enzymes
      has received a significant degree of attention owing to their capability to
      retain high enzymatic activity and stability. However, the relative lack of
      reusability due to the weakness of the flower-like structure has limited their
      practical applications. Herein, we have developed a simple but efficient method
      to synthesize highly robust enzyme-inorganic hybrid nanoflowers, which relies on
      further crosslinking of the enzyme molecules entrapped in the hybrid nanoflowers
      by treatment with glutaraldehyde (GA). By employing lipase from Candida rugosa as
      a model enzyme with copper phosphate during 3days incubation followed by the
      additional GA treatment for only 1h, we could successfully synthesize GA-treated
      lipase nanoflowers having similar flower-like morphology and hydrolytic activity
      (ca. 95% compared with the free lipase) as conventionally synthesized lipase
      nanoflowers without GA treatment. Importantly, the conventional lipase
      nanoflowers seemed not to be reusable because they lost most of their activity
      (~90%) after recycling 4 times, whereas GA-treated lipase nanoflowers exhibited
      higher retention of their initial activity (over 70%) after 4 reuses, which was
      also accompanied by an efficient maintenance of their flower-like morphology.
      Based on our results, we expect that this simple GA-mediated strategy to
      synthesize enzyme-inorganic hybrid nanoflowers can be readily extended to other
      enzymes for various biotechnological applications.

PMID- 28756858
TI  - Hydration-aggregation pretreatment for drastically improving esterification
      activity of commercial lipases in non-aqueous media.
AB  - We investigated a novel, simple method for activating lipases in non-aqueous
      reaction media. Lipase powders were suspended in n-fatty alcohols and were then
      hydrated by adding a small amount of water. A paste-like aggregate was recovered
      from the mixture followed by lyophilization for obtaining activated lipases as
      dry powders. Lipase activity was evaluated for esterification between myristic
      acid and methanol in n-hexane. The activated lipases exhibited high
      esterification activity depending on the experiment conditions during hydration
      aggregation pretreatment such as the amount of added water, the temperature, the
      pH of added buffer solutions, and the carbon chain length of the n-fatty alcohols
      used as pretreatment solvents. Various commercial lipases from different origins
      could be activated by this method. Changes in lipase conformation induced by the
      hydration-aggregation pretreatment were studied based on fluorescence and Fourier
      transform infrared spectroscopy.

PMID- 28756859
TI  - Improvement of activity and stability of Chondroitinase ABC I by introducing an
      aromatic cluster at the surface of protein.
AB  - Chondroitinase ABC I (ChABC I) has been shown to depolymerize a variety of
      glycosaminoglycan substrates and promote regeneration of damaged spinal cord.
      However, to date, intrathecal delivery methods have been suboptimal largely due
      to enzyme instability which necessitates repeated administration to the injured
      loci. Among the aromatic amino acids, tyrosine has been shown to be more
      effective in creation of stable clusters and further stabilize of the proteins.
      Bioinformatics approaches have been used to examine the effect of an extra
      aromatic cluster at the surface of ChABC I. In this study two amino acids i.e.,
      Asn806 and Gln810 were mutated to tyrosine and to alanine as negative control. In
      this way, four variants i.e., N806Y/Q810Y, N806A/Q810Y, N806Y/Q810A and
      N806A/Q810A were created. The results showed that N806Y/Q810Y mutation improved
      both activity and thermal stability of the enzyme while Ala substitution reduced
      the enzyme activity and destabilized it. Structural analysis of mutants showed an
      increase in intrinsic fluorescence intensity and secondary structure content of
      N806Y/Q810Y mutant when compared to the wild type enzyme indicating a more rigid
      structure of this variant. Moreover, the N806Y/Q810Y enzyme displayed a
      remarkable resistance against trypsin degradation with a half-life (t1/2) of
      45.0min versus 32.5min of wild-type. In conclusion, the data revealed that
      structural features and activity of ChABC I can be improved by introducing
      appropriate aromatic clusters at the surface of the enzyme.

PMID- 28756860
TI  - A quenched-flow system for measuring heterogeneous enzyme kinetics with sub
      second time resolution.
AB  - Even though many enzyme processes occur at the interface of an insoluble
      substrate, these reactions are generally much less studied than homogenous enzyme
      reactions in the aqueous bulk. Interfacial (or heterogeneous) enzyme reactions
      involve several reaction steps, and the established experimental approach to
      elucidate multi-step reactions is transient (or pre steady-state) kinetics. A key
      requirement for pre steady-state measurements is good time resolution, and while
      this has been amply achieved in different commercial instruments, they are
      generally not applicable to precipitating suspensions of insoluble substrate.
      Perhaps for this reason, transient kinetics has rarely been reported for
      heterogeneous enzyme reactions. Here, we describe a quenched-flow system using
      peristaltic pumps and stirred substrate suspensions with a dead time below 100ms.
      The general performance was verified by alkali catalyzed hydrolysis of 2,4
      dinitrophenyl acetate (DNPA), and the applicability to heterogeneous reactions
      was documented by two cellulases (Cel7A and Cel7B) acting on suspensions of
      microcrystalline cellulose (Avicel) at different loads up to 15g/l. The results
      showed distinctive differences between the two enzymes. In particular, we found
      that endo-lytic Cel7B combined very quickly with the substrate and reached the
      maximal activity within the dead-time of the instrument. Conversely, exo-lytic
      Cel7A showed a much slower initiation with maximal activity after 5-8s and a 10
      fold lower turnover. We suggest that the instrument may provide an important tool
      in attempts to elucidate the mechanism of cellulases and other enzymes' action on
      insoluble substrate.

PMID- 28756861
TI  - Immobilization-stabilization of a complex multimeric sucrose synthase from
      Nitrosomonas europaea. Synthesis of UDP-glucose.
AB  - Sucrose synthases (SuSys) can be used to synthesize cost-effective uridine 5'
      diphosphate glucose (UDP-glc) or can be coupled to glycosyltransferases (GTs) for
      the continuous recycling of UDP-glc. In this study, we present the first report
      of the immobilization-stabilization of a SuSy by multipoint covalent attachment.
      This stabilization strategy is very complex for multimeric enzymes because a very
      intense multipoint attachment can promote a dramatic loss of activity and/or
      stability. The homotetrameric SuSy from Nitrosomonas europaea (SuSyNe) was
      immobilized on a glyoxyl agarose support through two different orientations. The
      first occurred at pH 8.5 through the surface area containing the greatest number
      of amino termini from several enzyme subunits. The second orientation occurred at
      pH 10 through the region of the whole enzyme containing the highest number of Lys
      residues. The multipoint covalent immobilization of SuSy on glyoxyl agarose at pH
      10 provided a very significant stabilization factor under reaction conditions
      (almost 1000-fold more stable than soluble enzyme). Unfortunately, this important
      enzyme rigidification led to a dramatic loss of catalytic activity. A less
      stabilized conjugate, which was 65-fold more stable than the soluble form,
      preserved 64% of its initial catalytic activity. This derivative could be used
      for 3 reaction cycles and yielded approximately 210mM of UDP-glc per cycle. This
      optimal biocatalyst was modified with a polycationic polymer, polyethyleneimine
      (PEI), increasing its stability in the presence of the organic co-solvents
      necessary to glycosylate apolar antioxidants by GTs coupled to SuSy.

PMID- 28756862
TI  - Mutagenesis of Met-151 and Thr-153 to alanine in Thermoanaerobacter ethanolicus
      secondary alcohol dehydrogenase changes substrate specificity for acetophenones.
AB  - Secondary alcohol dehydrogenase (SADH) from Thermoanaerobacter ethanolicus
      reduces ketones to chiral alcohols, and generally obeys Prelog's Rule, with
      binding pockets for large and small alkyl substituents, giving (S)-alcohols. We
      have previously shown that mutations in both the large and small pockets can
      alter both substrate specificity and stereoselectivity. In the present work, Met
      151 and Thr-153, residues located in the small pocket, were mutated to alanine.
      The M151A mutant SADH shows significantly lower activity and lower
      stereoselectivity for reduction of aliphatic ketones than wild-type SADH.
      Furthermore, M151A showed non-linear kinetics for reduction of acetone. T153A
      SADH shows lower activity but similar stereoselectivity for ketone reduction
      compared to wild-type SADH. The I86A/M151A/C295A and I86A/T153A/C295A triple
      mutant SADH show altered specificity for reduction of substituted acetophenones.
      These results confirm that these mutations are useful to combine with I86A/C295A
      SADH to expand the small pocket of SADH and broaden the substrate specificity.

PMID- 28756863
TI  - Proline dehydrogenase-entrapped mesoporous magnetic silica nanomaterial for
      electrochemical biosensing of L-proline in biological fluids.
AB  - In this work, physical adsorption was used for immobilization of proline
      dehydrogenase onto a magnetic mesoporous silica nanomaterial. The immobilization
      and electrocatalytical activity of proline dehydrogenase entrapped in a magnetic
      mesoporous silica nanomaterial was studied using cyclic voltammetry, differential
      pulse voltammetry, and square wave voltammetry. The magnetic mesoporous silica
      networks having a high surface area (362m2g-1) exhibited excellent properties for
      entrapment of proline dehydrogenase. The applied approach led to better
      resistance to temperature and pH inactivation in comparison to the free enzyme.
      The electrocatalytic current response of proline dehydrogenase entrapped in a
      magnetic mesoporous silica nanomaterial toward oxidation of L-proline was
      maintained in the analytical solution temperature up to 70 degrees C. The
      entrapped proline dehydrogenase was casted onto a polycysteine-modified glassy
      carbon electrode. The electrode was evaluated as an electrochemical biosensor for
      electrooxidation and determination of L-proline in phosphate buffer solution. A
      cyclic voltammetry study indicated that the oxidation process of proline is
      irreversible and is diffusion controlled. The electrochemical behavior was
      further exploited as a sensitive detection scheme for L-proline determination by
      differential-pulse voltammetry. Under optimized conditions, the concentration
      range and detection limit were 0.01-0.15MUM and 0.006MUM, respectively. The
      method was applied to the assay of L-proline in whole blood and normal and
      malignant cell line lysates (normal cell (L929); gastric cancer cell-CAT 3, colon
      cancer cell-HCT, colon cancer cell-SW, and breast cancer cell-MCF7).

PMID- 28756865
TI  - Influence of remaining coronal tooth structure on fracture resistance and failure
      mode of restored endodontically treated maxillary incisors.
AB  - STATEMENT OF PROBLEM: Limited information is available on the effect of an
      incomplete ferrule because of the varying residual axial wall heights and the
      volume of residual tooth structure on the fracture resistance of endodontically
      treated and restored maxillary incisors. PURPOSE: The purpose of this in vitro
      investigation was to examine the effect of varying residual axial wall heights,
      residual coronal tooth structure, and the absence of 1 proximal axial wall on the
      fracture resistance and failure mode of endodontically treated teeth restored
      with metal posts. MATERIAL AND METHODS: Sixty intact human maxillary central
      incisors were divided into 6 groups (n=10): no ferrule (NF), 2-mm complete
      ferrule (CF2), 2-mm (IF2), 3-mm (IF3), and 4-mm (IF4) incomplete ferrules missing
      a single interproximal wall, and a control group that had a 6-mm incomplete
      ferrule (IF6). Cast metal post-and-cores were placed in all experimental
      specimens except for controls. Control specimens received 1 interproximal cavity
      preparation extending to the root canal access and a composite resin restoration.
      Complete metal crowns were then cemented on all specimens. Completed specimens
      were subjected to thermocycling (6000 cycles, 5 degrees C/55 degrees C) followed
      by the immediate testing of fracture resistance. Failed specimens were sectioned
      buccolingually and evaluated to identify the failure mode. The data were analyzed
      with an analysis of variance (ANOVA) and the Student-Newman-Keuls multiple
      comparison test (alpha=.05). RESULTS: An incomplete ferrule (IF2) with 1
      interproximal wall missing had significantly reduced fracture resistance (697 N)
      compared with a complete ferrule (932 N). An increase of 3 to 4 mm of remaining
      wall height improved fracture resistance, from 844 N (IF3) to 853 N (IF4).
      Partial decementation was noticed in 8 NF and 5 IF2 specimens. IF3 and IF4 had no
      decementations. Radicular fractures and cracks (catastrophic failure) were
      observed in all IF2, IF3, and IF4, 9 CF2, and 6 NF specimens. In 7 specimens
      without posts (IF6, control), composite resin foundation and/or coronal dentin
      fracture were observed and the failure was considered repairable. CONCLUSIONS:
      The results of this in vitro study indicated that specimens with a 2-mm ferrule
      of uniform height were more resistant to fracture than specimens with a 2-mm
      ferrule and 1 missing interproximal wall. An increased wall height of 3 or 4 mm
      was associated with a significant increase in fracture resistance and can
      compensate for the missing interproximal wall.

PMID- 28756864
TI  - Preparation and characterization of carbonic anhydrase-conjugated liposomes for
      catalytic synthesis of calcium carbonate particles.
AB  - The biomimetic approach using immobilized enzymes is useful for the synthesis of
      structurally defined inorganic materials. In this work, carbonic anhydrase (CA)
      from bovine erythrocytes was covalently conjugated at 25 degrees C to the
      liposomes composed of 15mol% 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphoethanolamine-N-(glutaryl) (NG-POPE), and the zwitterionic and anionic
      phospholipids with the same acyl chains as NG-POPE. For the conjugation, the
      carboxyl groups of liposomal NG-POPE were activated with 11mM 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC) and 4.6mM N-hydroxysulfosuccinimide (sulfo
      NHS). The carbonic anhydrase-conjugated liposomes (CALs) with the mean
      hydrodynamic diameter of 149nm showed the esterase activity corresponding to on
      average 5.5*102 free CA molecules per liposome. On the other hand, the intrinsic
      fluorescence and absorbance measurements consistently revealed that on average
      1.4*103 CA molecules were conjugated to a liposome, suggesting that the molecular
      orientation of enzyme affected its activity. The formation of calcium carbonate
      particles was significantly accelerated by the CALs ([lipid]=50MU M) in the 0.3M
      Tris solution at 10-40 degrees C with dissolved CO2 (~17mM) and CaCl2 (46mM). The
      anionic CALs were adsorbed with calcium as revealed with the zeta-potential
      measurements. The CAL system offered the calcium-rich colloidal interface where
      the bicarbonate ions were catalytically produced by the liposome-conjugated CA
      molecules. The CALs also functioned in the external loop airlift bubble column
      operated with a model flue gas (10vol/vo% CO2), yielding partly agglomerated
      calcium carbonate particles as observed with the scanning electron microscopy
      (SEM).

PMID- 28756866
TI  - Tuberculosis, granulomatosis with polyangiitis, or both? A case report.
AB  - INTRODUCTION: Tuberculosis (TB) is a chronic granulomatose infection, and
      granulomatosis with polyangiitis (GP) is a small vessel vasculitis, both of which
      affect the lungs. The combination of these diseases is rare. Both have similar
      clinical features, making the differential diagnosis difficult. CASE REPORT: It
      concerns a 37 year-old female undergoing treatment for pulmonary TB, who
      presented with left ocular proptosis, eyelid and conjunctival edema and erythema.
      Orbital biopsy revealed GP. C-Anti-neutrophil cytoplasmic antibodies were
      elevated. The patient responded well to immunosuppressive treatment. CONCLUSION:
      TB and GP can associate. Diagnosis should include not only C-anti-neutrophil
      cytoplasmic antibodies, but also a biopsy, in order to select the appropriate
      treatment.

PMID- 28756867
TI  - [Therapeutic drug monitoring - 4th edition of the congress of pharmacology of
      anticancer drugs].

PMID- 28756868
TI  - Intravagal Parathyroid Adenoma With Direct Surgery.

PMID- 28756870
TI  - Anti-C1q autoantibodies in patients with neuromyelitis optica spectrum disorders.
AB  - We examined anti-complement C1q (C1q) autoantibody levels in serum and
      cerebrospinal fluid (CSF) samples of patients with neuromyelitis optica spectrum
      disorders (NMOSD). We analyzed the correlations between anti-C1q autoantibody
      levels and the clinical and other CSF characteristics of NMOSD. Serum and CSF
      anti-C1q autoantibody levels increased during the acute phase of NMOSD, reverting
      to the same levels as controls during remission. CSF anti-C1q autoantibody levels
      during the acute phase correlated with several markers reflecting disease
      severity, Expanded Disability Status Scale worsening, spinal cord lesion length
      in cases with myelitis, CSF protein and interleukin-6 levels, and CSF/serum
      albumin ratios.

PMID- 28756869
TI  - Converging Prefronto-Insula-Amygdala Pathways in Negative Emotion Regulation in
      Marmoset Monkeys.
AB  - BACKGROUND: Impaired regulation of emotional responses to potential threat is a
      core feature of affective disorders. However, while the subcortical circuitry
      responsible for processing and expression of fear has been well characterized,
      the top-down control of this circuitry is less well understood. Our recent
      studies demonstrated that heightened emotionality, as measured both
      physiologically and behaviorally, during conditioned fear and innate/social
      threat was induced, independently, by excitotoxic lesions of either the anterior
      orbitofrontal cortex (antOFC) or ventrolateral prefrontal cortex (vlPFC). An
      important outstanding question is whether the antOFC and vlPFC act on common or
      distinct downstream targets to regulate negative emotion. METHODS: The question
      was addressed by combining localized excitotoxic lesions in the PFC of a nonhuman
      primate and functional neuroimaging ([18F]fluorodeoxyglucose positron emission
      tomography) with a fear-regulating extinction paradigm. Marmoset monkeys with
      unilateral lesions of either the antOFC or vlPFC were scanned immediately
      following exposure to a fearful or safe context, and differences in
      [18F]fluorodeoxyglucose uptake were evaluated. RESULTS: [18F]fluorodeoxyglucose
      uptake in the insula and amygdala of the intact hemisphere was significantly
      increased in response to the fearful context compared with the safe context. Such
      discrimination between the two contexts was not reflected in the activity of the
      insula-amygdala of the antOFC or vlPFC-lesioned hemisphere. Instead, uptake was
      at an intermediate level in both contexts. CONCLUSIONS: These findings
      demonstrate that the distinct control functions of the antOFC and vlPFC converge
      on the same downstream targets to promote emotion regulation, taking us closer to
      a mechanistic understanding of different forms of anxiety.

PMID- 28756871
TI  - Randomized phase IIB evaluation of weekly paclitaxel versus weekly paclitaxel
      with oncolytic reovirus (Reolysin(r)) in recurrent ovarian, tubal, or peritoneal
      cancer: An NRG Oncology/Gynecologic Oncology Group study.
AB  - OBJECTIVE: To assess whether the addition of oncolytic reovirus (Reolysin(r)) to
      weekly paclitaxel prolonged progression-free survival (PFS) in the treatment of
      women with recurrent or persistent ovarian, tubal or primary peritoneal cancer.
      PATIENTS AND METHODS: Patients with recurrent or persistent epithelial ovarian,
      tubal, or peritoneal carcinoma, measurable or detectable disease, and three or
      fewer prior regimens were randomly assigned to paclitaxel (80mg/m2 intravenously
      days 1, 8, and 15 every 4weeks) or the combination of paclitaxel (80mg/m2
      intravenously days 1, 8, and 15) plus reovirus 3*1010TCID50/day intravenously on
      days 1-5, both every 4weeks until disease progression or toxicity. The primary
      end point was PFS. The study was designed with 80% power for a one-sided
      alternative at a 10% level of significance to detect a reduction in the hazard by
      37.5%. RESULTS: The study accrued 108 patients, 100 of whom were evaluable for
      toxicity. Median PFS was 4.3months for paclitaxel and 4.4months for paclitaxel
      plus reovirus (hazard ratio, 1.11; 90% two-sided CI, 0.78 to 1.59; one-sided
      P=0.687). The proportion responding (overall response rate) to paclitaxel was 20%
      among 45 patients with measurable disease receiving paclitaxel alone, and 17.4%
      among the 46 patients treated with the combination. The asymptotic relative
      probability of responding was 0.87 (90% CI, 0.42 to 1.79). Severe adverse events
      were more common in the combination regimen than in paclitaxel arm for severe
      neutropenia (grade>=4, 12% versus 0%), and severe respiratory adverse events
      (grade>=3, 25% versus 2%). No deaths were considered treatment related.
      CONCLUSION: The addition of reovirus to weekly paclitaxel in the treatment of
      women with recurrent or persistent ovarian, tubal or peritoneal cancer did not
      sufficiently reduce the hazard of progression or death to warrant further
      investigation.

PMID- 28756873
TI  - Accordion technique combined with minimally invasive percutaneous decortication
      for the treatment of bone non-union.
AB  - BACKGROUND: A variety of approaches have been used to treat oligotrophic or
      atrophic non-union. Conventional methods are often associated with great
      operative trauma, increased blood loss, a risk of re-infection, higher medical
      costs, and complications at the donor site. This study aimed to assess the
      clinical efficacy of the accordion technique combined with Minimally Invasive
      Percutaneous Decortication (MIPD) for these types of bone non-union. METHODS:
      From January 2010 to December 2015, 20 patients with long bone aseptic non-unions
      of the lower extremities without bone defects who were treated with the accordion
      technique combined with MIPD. The limb-length discrepancy (LLD) was less than 2cm
      in all patients. None of the patients received autogenous bone grafts during
      follow-up. All surgeries were performed by the same surgeon, and the modified
      Application of methods of Ilizarov (ASAMI) criteria were used to evaluate the
      operative effectiveness. RESULTS: A total of 20 patients were included in this
      study, and 1 patient was lost during follow-up. Fifteen of these patients
      presented with oligotrophic non-unions, and 5 patients presented with atrophic
      non-unions. The average follow-up period in these patients was 12.1 months
      (range: 8-42 months). The alternative compression and distraction procedure was
      repeated 1-3 times. Blood loss was 30 to 250ml during surgery. Ultimately, bone
      union was achieved in 19 patients and failed in 1 patient. The fractures healed
      within 4-8 months (average time: 5.9 months), and fracture healing was considered
      excellent in 19 patients and poor in 1 patient. Postoperative function was
      evaluated as excellent in 9 patients, good in 6 patients, fair in 4 patients, and
      poor in 1 patient. CONCLUSION: The accordion technique combined with MIPD, which
      is a simple, minimally invasive procedure that does not require autologous bone
      grafting, resulted in a high bone union rate and good postoperative function.

PMID- 28756874
TI  - Diagnostic Value of Neurological Studies in Diagnosing Syncope: A Systematic
      Review.
AB  - BACKGROUND: Syncope is common and approaches to establishing etiology remain a
      matter of clinical and financial importance. Patients often undergo comprehensive
      neurologic investigations despite a lack of compelling indications. The aim was
      to determine the prevalence of use and diagnostic yield of electroencephalography
      (EEG), head computed tomography (CT), head magnetic resonance imaging (MRI), and
      carotid Doppler ultrasound (CUS) examinations. METHODS: We conducted a systematic
      search in EMBASE, PubMed, and Cochrane from 1970 to 2015 for studies reporting on
      the use of EEG, CT, MRI, and CUS in diagnosing the cause of syncope. The
      inclusion criteria were: (1) observational and randomized trials; (2) frequency
      of use of investigations; and (3) diagnostic yield. Diagnostic studies of the
      more general transient loss of consciousness were excluded. RESULTS: Of 149
      screened studies, 15 studies having 6944 patients met the criteria. No studies
      met all 6 prespecified quality descriptors. The mean prevalence of test use were:
      EEG, 17.0%; CT, 57.3%; MRI, 10.5%; and CUS, 17.8%. The articles reported the
      likelihoods of a test providing diagnostic information for syncope etiology were:
      EEG, 1.35%; CT, 1.18%; MRI, 3.74%; and CUS, 2.4%. Only 2 new and informative
      results were noted in 6334 tests. CONCLUSIONS: Neurologic investigations for
      assessment of patients deemed to have syncope are used widely and are widely
      ineffective. Neurologic investigations should be obtained only with a very high
      degree of clinical suspicion.

PMID- 28756872
TI  - Retinoic acid improves nephrotoxic serum-induced glomerulonephritis through
      activation of podocyte retinoic acid receptor alpha.
AB  - Proliferation of glomerular epithelial cells, including podocytes, is a key
      histologic feature of crescentic glomerulonephritis. We previously found that
      retinoic acid (RA) inhibits proliferation and induces differentiation of
      podocytes by activating RA receptor-alpha (RARalpha) in a murine model of HIV
      associated nephropathy. Here, we examined whether RA would similarly protect
      podocytes against nephrotoxic serum-induced crescentic glomerulonephritis and
      whether this effect was mediated by podocyte RARalpha. RA treatment markedly
      improved renal function and reduced the number of crescentic lesions in nephritic
      wild-type mice, while this protection was largely lost in mice with podocyte
      specific ablation of Rara (Pod-Rara knockout). At a cellular level, RA
      significantly restored the expression of podocyte differentiation markers in
      nephritic wild-type mice, but not in nephritic Pod-Rara knockout mice.
      Furthermore, RA suppressed the expression of cell injury, proliferation, and
      parietal epithelial cell markers in nephritic wild-type mice, all of which were
      significantly dampened in nephritic Pod-Rara knockout mice. Interestingly, RA
      treatment led to the coexpression of podocyte and parietal epithelial cell
      markers in a small subset of glomerular cells in nephritic mice, suggesting that
      RA may induce transdifferentiation of parietal epithelial cells toward a podocyte
      phenotype. In vitro, RA directly inhibited the proliferation of parietal
      epithelial cells and enhanced the expression of podocyte markers. In vivo lineage
      tracing of labeled parietal epithelial cells confirmed that RA increased the
      number of parietal epithelial cells expressing podocyte markers in nephritic
      glomeruli. Thus, RA attenuates crescentic glomerulonephritis primarily through
      RARalpha-mediated protection of podocytes and in part through the inhibition of
      parietal epithelial cell proliferation and induction of their
      transdifferentiation into podocytes.

PMID- 28756875
TI  - Glycopattern analysis of acidic secretion in the intestine of the red-eared
      slender turtle; Trachemys scripta elegans (Testudines: Emydidae).
AB  - The secretion of the goblet cells in the intestine of Trachemys scripta elegans
      was studied in situ by histochemical methods to analyze the diversity of sugar
      chains, with particular regard to the acidic glycans. Conventional histochemical
      stains (Periodic acid-Schiff, Alcian Blue pH 2.5, High Iron Diamine) and binding
      with ten FITC-labelled lectins combined with chemical and enzymatic pre
      treatments were used to characterize the oligosaccharidic chains. The intestine
      can be divided into three regions, i.e. a duodenum, a small intestine and a large
      intestine. Goblet cells were observed in all the three tracts and presented an
      acidic secretion. WGA, LFA, PNA and SBA binding was observed only after
      desulfation. Glycans secreted by the three tracts consist mainly of
      sulfosialomucins with 1,2-linked fucose, mannosylated, glucosaminylated and
      subterminal galactosyl/galactosaminylated residuals. Differences among tracts are
      quantitative rather than qualitative, with sulfated, galactosaminylated and
      glycosaminylated residuals increasing from duodenum to large intestine, and
      galactosylated and fucosylated residuals showing an opposite trend. Variation is
      observed also between apices and bases of villi in both duodenum and small
      intestine, where sulphation decreases from the base to the apex and glycosylation
      shows an opposite trend. Functional implication of these findings is discussed in
      a comparative context.

PMID- 28756876
TI  - Combating atherosclerosis with heavy PUFAs: Deuteron not proton is the first.

PMID- 28756877
TI  - Platelet populations and priming in hematological diseases.
AB  - In healthy subjects and patients with hematological diseases, platelet
      populations can be distinguished with different response spectra in hemostatic
      and vascular processes. These populations partly overlap, and are less distinct
      than those of leukocytes. The platelet heterogeneity is linked to structural
      properties, and is enforced by inequalities in the environment. Contributing
      factors are variability between megakaryocytes, platelet ageing, and positive or
      negative priming of platelets during their time in circulation. Within a
      hemostatic plug or thrombus, platelet heterogeneity is enhanced by unequal
      exposure to agonists, with populations of contracted platelets in the thrombus
      core, discoid platelets at the thrombus surface, patches of ballooned and
      procoagulant platelets forming thrombin, and coated platelets binding fibrin.
      Several pathophysiological hematological conditions can positively or negatively
      prime the responsiveness of platelet populations. As a consequence, in vivo and
      in vitro markers of platelet activation can differ in thrombotic and
      hematological disorders.

PMID- 28756878
TI  - Heme oxygenase-1: A new druggable target in the management of chronic and acute
      myeloid leukemia.
AB  - Heme oxygenase-1 (HO-1) is the enzyme catalyzing the rate-limiting oxidative
      degradation of cellular heme into free iron, carbon monoxide (CO), and
      biliverdin, which is then rapidly converted into bilirubin. By means of these
      catabolic end-products and by removal of pro-oxidant heme, HO-1 exerts
      antioxidant, antiapoptotic, and immune-modulating effects, leading to overall
      cytoprotective and beneficial functions in mammalian cells. Therefore, HO-1 is
      considered a survival molecule in various stress-related conditions. By contrast,
      growing evidence suggests that HO-1 is a survival-enhancing molecule also in
      various solid and blood cancers, such as various types of leukemia, promoting
      carcinogenesis, tumor progression, and chemo-resistance. Among leukemias, chronic
      myeloid leukemia (CML) is currently therapeutically well treated with tyrosine
      kinase inhibitors (TKIs) such as Imatinib (IM) and its congeners; nevertheless,
      resistance to all kinds of current drugs persist in a number of patients.
      Moreover, treatment outcomes for acute myeloid leukemia (AML) remain
      unsatisfactory, despite progress in chemotherapy and hematopoietic stem cell
      transplantation. Therefore, identification of new eligible targets that may
      improve leukemias therapy is of general interest. Several recent papers prove
      that inhibition of HO-1 through HO-1 inhibitors as well as modulation of other
      pathways involving HO-1 by a number of different new or known molecules, are
      critical for leukemia treatment. This review summarizes the current understanding
      of the pro-tumorigenic role of HO-1 and its potential as a molecular target for
      the treatment of leukemias.

PMID- 28756879
TI  - [Histoseminar on inflammatory bowel diseases (IBD): Case no 02].

PMID- 28756880
TI  - Is it time to extend synoptic reporting to include potentially preneoplastic oral
      epithelial and lichenoid lesions?

PMID- 28756881
TI  - Self-reported oral health and xerostomia in adult patients with celiac disease
      versus a comparison group.
AB  - OBJECTIVES: This study aimed to assess the impact of celiac disease (CD) on oral
      health and xerostomia. STUDY DESIGN: Members of the Dutch Celiac Society (n =
      5522) were invited to complete an online questionnaire based on the Oral Health
      Impact Profile 14 (OHIP-14) and Xerostomia Inventory (XI). Acquaintances and
      partners of the CD respondents served as the comparison group. In total, data of
      740 patients with CD and 270 comparison participants were evaluated. RESULTS: The
      median age of the responding patients with CD (55 years) was similar to the
      median age in the comparison group (53 years). Oral health problems, including
      aphthous stomatitis, painful mouth, and gingival problems, were more frequently
      reported by patients with CD. Mean OHIP-14 score (4.9 vs 2.6; P < .001) and the
      mean XI score (22.2 vs 17.2; P < .001) were higher in the CD group than in the
      comparison group. No significant effects of gender, age at CD diagnosis, or time
      on a gluten-free diet in mean OHIP-14 and XI scores were observed. CONCLUSIONS:
      This study showed that oral health problems are more commonly experienced in
      adult patients with CD than in the comparison group. Collaboration between
      dentists and gastroenterologists is recommended to increase detection of
      undiagnosed CD.

PMID- 28756882
TI  - Cell genomics and immunosuppressive biomarker expression influence PD-L1
      immunotherapy treatment responses in HNSCC-a computational study.
AB  - OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is correlated with
      objective response rates to PD-1 and PD-L1 immunotherapies. However, both
      immunotherapies have only demonstrated 12%-24.8% objective response rates in
      patients with head and neck squamous cell carcinoma (HNSCC), demonstrating a need
      for a more accurate method to identify those who will respond before their
      therapy. Immunohistochemistry to detect PD-L1 reactivity in tumors can be
      challenging, and additional methods are needed to predict and confirm PD-L1
      expression. Here, we hypothesized that HNSCC tumor cell genomics influences cell
      signaling and downstream effects on immunosuppressive biomarkers and that these
      profiles can predict patient clinical responses. STUDY DESIGN: We identified
      deleterious gene mutations in SCC4, SCC15, and SCC25 and created cell line
      specific predictive computational simulation models. The expression of 24
      immunosuppressive biomarkers were then predicted and used to sort cell lines into
      those that would respond to PD-L1 immunotherapy and those that would not.
      RESULTS: SCC15 and SCC25 were identified as cell lines that would respond to PD
      L1 immunotherapy treatment and SCC4 was identified as a cell line that would not
      likely respond to PD-L1 immunotherapy treatment. CONCLUSIONS: This approach, when
      applied to HNSCC cells, has the ability to predict PD-L1 expression and predict
      PD-1- or PD-L1-targeted treatment responses in these patients.

PMID- 28756883
TI  - Caspofungin Treatment for Pulmonary Invasive Fungal Disease in Hematology
      Patients: A Retrospective Study in a Clinical Practice Setting in China.
AB  - PURPOSE: Invasive fungal disease (IFD) is a serious complication in patients with
      hematologic malignancies. Caspofungin is the first approved inhibitor of fungal
      beta-1,3-glucan synthesis. The aim of the present study was to evaluate the
      effectiveness of caspofungin in the treatment of IFD in patients with hematologic
      malignancies. METHODS: In this retrospective study, data from the electronic
      medical records of 1118 inpatients who were admitted to 10 hospitals in China
      between 2013 and 2014 were analyzed. Inclusion criteria were hematologic disorder
      and IFD diagnosed during the hospitalization, based on clinical manifestations or
      evidence of pulmonary invasion, as well as caspofungin treatment for at least 7
      days. The primary end point was the favorable response rate at the end of
      caspofungin as initial therapy for proven/probable/possible pulmonary IFD. The
      secondary end point was the survival rate after the completion of the caspofungin
      treatments. FINDINGS: A total of 704 patients were included, of whom 122 had IFD
      classified as probable/possible and 582 had unclassified IFD. The most frequent
      hematologic diseases were acute myeloid leukemia (42.8%), followed by acute
      lymphatic leukemia (18.8%), non-Hodgkin lymphoma (8.8%), aplastic anemia (7.1%),
      and others (22.5%). The rates of favorable caspofungin response were 57.2% in all
      patients, 58.2% in the probable/possible IFD group, and 57.0% in the unclassified
      IFD group. Caspofungin as initial monotherapy led to a favorable response rate of
      62.2% in the probable/possible IFD group. Uni- and multivariate analyses revealed
      that not recovering from neutropenia during antifungal treatment, and advanced
      age, were significant factors for unfavorable outcomes. The overall IFD-related
      mortality rate was 4.1%. IMPLICATIONS: The results of our study show that
      caspofungin treatment of IFD in hematology patients was reasonable, with an
      overall rate of favorable response of 57.2% with each caspofungin treatment
      strategy.

PMID- 28756884
TI  - [Familial keratolytic winter erythema: A cathepsin at the controls].

PMID- 28756885
TI  - [Sporadic infantile myofibromatosis: Mutations with PDGFRB gain-of-function].

PMID- 28756886
TI  - Reply to: Radioiodine ablation necessary for patients with low-risk papillary
      thyroid carcinoma and tumor >4 cm?

PMID- 28756887
TI  - [Results of bronchiectasis surgery: About 64 cases].
AB  - INTRODUCTION: Bronchiectasis is a serious and disabling disease. Surgical
      treatment is an interesting alternative to be proposed early to patients in case
      of complications or deterioration of quality of life, despite an optimal medical
      treatment. Through this retrospective study and literature review, we analyze
      surgical results for bronchiectasis. PATIENTS AND METHOD: We conducted a
      monocentric, retrospective, descriptive and analytical study in the Department of
      thoracic surgery of CHU Hassan II Fes, about 64 patients operated for
      bronchiectasis during the period from January 2009 to December 2016. RESULTS:
      There were 30 men and 34 women with an average age of 32years. Twenty six percent
      (26 %) had a history of recurrent lung infection, and 17.18 % would have been
      treated for pulmonary tuberculosis and declared cured. Productive cough (93 %),
      morning chronic bronchorrhea (92 %) and repeatedly hemoptysis (62.5 %) were the
      main symptoms. On CT scanning, the bronchiectasis was unilateral and localized in
      49 cases. The right lung was involved in 27 cases and the location was bilateral
      in 15 cases. It was 38 cystic bronchiectasis, 16 cylindrical bronchiectasis, and
      10 mixed lesions predominantly cylindrical. The flexible bronchoscopy carried out
      in 34 cases, had shown a carcinoid tumor in 1 case, a bronchiolithiasis in 1 case
      and a intrabronchial foreign body in 1 case. The incision was a conservative
      posterolateral thoracotomy in all cases. The performed surgical procedure was
      lobectomy in 53 % of patients. The morbidity rate was 32.80 % and dominated by
      septic complications. After a mean follow-up of 20.52months, 2 cases of
      recurrence minimal hemoptysis and 1 case of renewed bronchorrhea are noted. For
      all other patients the outcome was favorable and no deaths have been noted to
      date. CONCLUSION: The surgery of bronchiectasis requires a perfect collaboration
      between the pulmonologist, the thoracic surgeon, the anesthesiologist, the
      biologist and particularly the physiotherapist for an optimal care of patients.

PMID- 28756888
TI  - [Can Tako-tsubo syndrome be integrated into post-pneumonectomy syndrome?]
AB  - INTRODUCTION: Tako-tsubo syndrome, or "left ventricular transitory apical balloon
      syndrome", is an acute coronary syndrome with normal coronary arteries.
      OBSERVATION: We report the case of a 50-year-old patient operated for a post
      tuberculous destroyed lung, for which she had a left pneumonectomy. Six months
      later, she presented with chest pain complicated by cardiorespiratory arrest. The
      Tako-tsubo syndrome was retained after eliminating the other causes. CONCLUSION:
      The diagnosis of Tako-tsubo syndrome should be considered before the sudden
      occurrence of an acute coronary syndrome in the aftermath of stress or emotional
      shock.

PMID- 28756889
TI  - [Unusual association of two paraneoplastic syndromes in lung adenocarcinoma:
      Acquired ichtyosis and hypertrophic pulmonary osteoarthropathy].

PMID- 28756890
TI  - Protein separations using enhanced-fluidity liquid chromatography.
AB  - Enhanced-fluidity liquid chromatography (EFLC) methods using methanol/H2O/CO2 and
      hydrophilic interaction liquid chromatography (HILIC) were explored for the
      separation of proteins and peptides. EFLC is a separation mode that uses a mobile
      phase made of conventional solvents combined with liquid carbon dioxide (CO2) in
      subcritical conditions. The addition of liquid CO2 enhances diffusivity and
      decreases viscosity while maintaining mixture polarity, which typically results
      in reduced time of analysis. TFA additive and elevated temperature were leveraged
      as key factors in the separation of a 13-analyte intact protein mixture in under
      5min. Under these conditions EFLC showed modest improvement in terms of peak
      asymmetry and analysis time over the competing ACN/H2O separation. Protein
      analytes detected by electrospray ionization - quadrupole time of flight, were
      shown to be unaffected by the addition of CO2 in the mobile phase. Herein, the
      feasibility of separating hydrophilic proteins up to 80kDa (with transferrin) is
      demonstrated for CO2-containing mobile phases.

PMID- 28756891
TI  - Identification and deconvolution of carbohydrates with gas chromatography-vacuum
      ultraviolet spectroscopy.
AB  - Methodology for qualitative and quantitative determination of carbohydrates with
      gas chromatography coupled to vacuum ultraviolet detection (GC-VUV) is presented.
      Saccharides have been intently studied and are commonly analyzed by gas
      chromatography-mass spectrometry (GC-MS), but not always effectively. This can be
      attributed to their high degree of structural complexity: alpha/beta anomers from
      their axial/equatorial hydroxyl group positioning at the C1-OH and flexible ring
      structures that lead to the open chain, five-membered ring furanose, and six
      membered ring pyranose configurations. This complexity can result in convoluted
      chromatograms, ambiguous fragmentation patterns and, ultimately, analyte
      misidentification. In this study, mono-, di, and tri-saccharides were derivatized
      by two different methods-permethylation and oximation/pertrimethylsilylation-and
      analyzed by GC-VUV. These two derivatization methods were then compared for their
      efficiency, ease of use, and robustness. Permethylation proved to be a useful
      technique for the analysis of ketopentoses and pharmaceuticals soluble in
      dimethyl sulfoxide (DMSO), while the oximation/pertrimethylsilylation method
      prevailed as the more promising, overall, derivatization method. VUV spectra have
      been shown to be distinct and allow for efficient differentiation of isomeric
      species such as ketopentoses and reducing versus non-reducing sugars. In addition
      to identification, pharmaceutical samples containing several compounds were
      derivatized and analyzed for their sugar content with the GC-VUV technique to
      provide data for qualitative analysis.

PMID- 28756892
TI  - Fast, sensitive, and selective gas chromatography tandem mass spectrometry method
      for the target analysis of chemical secretions from femoral glands in lizards.
AB  - Chemical signaling is a widespread mode of communication among living organisms
      that is used to establish social organization, territoriality and/or for mate
      choice. In lizards, femoral and precloacal glands are important sources of
      chemical signals. These glands protrude chemical secretions used to mark
      territories and also, to provide valuable information from the bearer to other
      individuals. Ecologists have studied these chemical secretions for decades in
      order to increase the knowledge of chemical communication in lizards. Although
      several studies have focused on the chemical analysis of these secretions, there
      is a lack of faster, more sensitive and more selective analytical methodologies
      for their study. In this work a new GC coupled to tandem triple quadrupole MS (GC
      QqQ (MS/MS)) methodology is developed and proposed for the target study of 12
      relevant compounds often found in lizard secretions (i.e. 1-hexadecanol, palmitic
      acid, 1-octadecanol, oleic acid, stearic acid, 1-tetracosanol, squalene, cholesta
      3,5-diene, alpha-tocopherol, cholesterol, ergosterol and campesterol). The method
      baseline-separated the analytes in less than 7min, with instrumental limits of
      detection ranging from 0.04 to 6.0ng/mL. It was possible to identify differences
      in the composition of the samples from the lizards analyzed, which depended on
      the species, the habitat occupied and the diet of the individuals. Moreover,
      alpha-tocopherol has been determined for the first time in a lizard species,
      which was thought to lack its expression in chemical secretions. Globally, the
      methodology has been proven to be a valuable alternative to other published
      methods with important improvements in terms of analysis time, sensitivity, and
      selectivity.

PMID- 28756893
TI  - (+) or (-)-1-(9-fluorenyl)ethyl chloroformate as chiral derivatizing agent: A
      review.
AB  - Over the last 30years, (+/-)-1-(9-fluorenyl)ethyl chloroformate ((+/-)-FLEC) was
      used as a chiral derivatizing agent in various analytical applications involving
      a wide range of endogenous, pharmaceutical and environmentally relevant
      molecules. This comprehensive review aims to present all the significant aspects
      related to the state of the art in FLEC labeling and subsequent chiral separation
      of the resulting diastereomers using LC, SFC and CE techniques.

PMID- 28756894
TI  - Spatial distribution of mast cells and macrophages around tumor glands in human
      breast ductal carcinoma.
AB  - Macrophages and mast cells are usually present in the tumor microenvironment and
      play an important role as regulators of inflammation, immunological response and
      angiogenesis in the tumor microenvironment. In this study, we have evaluated
      macrophage, mast cell, and microvessel density in a selected group of different
      grade of invasive breast carcinoma tumor specimens. Furthermore, we have
      investigated the pattern of distribution of CD68-positive macrophages and
      tryptase-positive mast cells around tumor glands. Results have shown that: A)
      Macrophages are more numerous in G2 and G3 breast cancer stages respect to
      controls, the per cent of macrophages in G1 samples was comparable to the
      controls, and the spatial relationship between macrophages and glands (as
      indicated by the mean cell-to-gland distance) correlated with CD31-positive
      vessels. B) Mast cells in G2 and G3 tumor specimens show a significant increase
      in their number as compared to control samples, and their spatial distribution
      around the glands did not show any significant difference among groups. Overall,
      the results of this study confirm the important role of macrophages and mast
      cells in tumor progression and angiogenesis in human ductal breast cancer, and
      pointed out the spatial relationship between tumor macrophages and glands, and
      its correlation with microvascular density.

PMID- 28756895
TI  - Stigma and Health-Related Quality of Life in Sexual Minorities.
AB  - INTRODUCTION: Stigma against sexual minorities is well documented, but its long
      term consequences for health-related quality of life (HRQL) are unknown. This
      study examined stigma-related predictors of sexual orientation disparities in
      HRQL and their contribution to young adult HRQL disparities. METHODS: In 2013,
      participants (N=7,304, aged 18-31 years) reported sexual orientation (completely
      heterosexual [CH], mostly heterosexual, bisexual, and lesbian/gay). The EQ5D-5L,
      preference weighted for the U.S. population, was used to assess HRQL (range, 
      0.109 [worse than dead] to 1 [full health]). In prior waves conducted during
      adolescence, participants reported past-year bullying victimization (range, 1
      [never] to 5 [several times/week]) and subjective social status (SSS) in their
      school (range, 1 [top] to 10 [bottom]). Analyses conducted in 2016 used
      longitudinal, multivariable linear and logistic regression to assess the
      contribution of bullying victimization and SSS in adolescence to sexual
      orientation disparities in HRQL in young adulthood, controlling for confounders
      and stratified by gender. RESULTS: Compared with CHs, both female and male sexual
      minorities reported more bullying victimization and lower SSS in adolescence and
      lower HRQL in young adulthood (HRQL score among women: mostly heterosexual,
      0.878; bisexual, 0.839; lesbian, 0.848; CH, 0.913; HRQL score among men: mostly
      heterosexual, 0.877; bisexual, 0.882; gay, 0.890; CH, 0.925; all p-values <0.05).
      When bullying and SSS were added into multivariable models, orientation group
      effect estimates were attenuated substantially, suggesting bullying and lower SSS
      in adolescence partly explained HRQL disparities in young adulthood. CONCLUSIONS:
      Stigma-related experiences in adolescence may have lasting adverse effects on
      sexual minority health in adulthood.

PMID- 28756896
TI  - Differences in U.S. Suicide Rates by Educational Attainment, 2000-2014.
AB  - INTRODUCTION: The purpose of this study was to document the association between
      education and suicide risk, in light of rising suicide rates and socioeconomic
      differentials in mortality in the U.S. METHODS: Differentials and trends in U.S.
      suicide rates by education were examined from 2000 to 2014 using death
      certificate data on 442,135 suicides from the National Center for Health
      Statistics and Census data. Differences in the circumstances and characteristics
      of suicide deaths by education were investigated using 2013 data from the
      National Violent Death Reporting System for nine states. Analyses were conducted
      in 2016. RESULTS: Between 2000 and 2014, men and women aged >=25 years with at
      least a college degree exhibited the lowest suicide rates; those with a high
      school degree displayed the highest rates. Men with a high school education were
      twice as likely to die by suicide compared with those with a college degree in
      2014. The education gradient in suicide mortality generally remained constant
      over the study period. Interpersonal/relationship problems and substance abuse
      were more common circumstances for less educated decedents. Mental health issues
      and job problems were more prevalent among college-educated decedents.
      CONCLUSIONS: The findings highlight the importance of social determinants in
      suicide risk, with important prevention implications.

PMID- 28756897
TI  - Role of CD11c+ T-bet+ B cells in human health and disease.
AB  - A growing body of evidence suggests that when B cells are chronically stimulated,
      a phenotypically unique subset expands. Data suggest that this atypical
      population contains B cell receptor (BCR) specificities capable of binding the
      antigen, or sets of antigens that initiated the expansion of these cells. These B
      cells have been given various names, including double negative B cells, atypical
      memory B cells, tissue-like memory B cells, or age associated B cells (ABCs).
      However, on close inspection these reports described B cell subsets that closely
      resemble B cells we refer to as CD11c+ B cells that often express T-bet. Here we
      will review the human studies that describe atypical memory B cells and compare
      and contrast their phenotype and suggested function in health and disease.

PMID- 28756898
TI  - Paving the way for a gold standard of care for infertility treatment: improving
      outcomes through standardization of laboratory procedures.
AB  - Infertility affects over 70 million couples globally. Access to, and interest in,
      assisted reproductive technologies is growing worldwide, with more couples
      seeking medical intervention to conceive, in particular by IVF. Despite numerous
      advances in IVF techniques since its first success in 1978, almost half of the
      patients treated remain childless. The multifactorial nature of IVF treatment
      means that success is dependent on many variables. Therefore, it is important to
      examine how each variable can be optimized to achieve the best possible outcomes
      for patients. The current approach to IVF is fragmented, with various protocols
      in use. A systematic approach to establishing optimum best practices may improve
      IVF success and live birth rates. Our vision of the future is that technological
      advancements in the laboratory setting are standardized and universally adopted
      to enable a gold standard of care. Implementation of best practices for
      laboratory procedures will enable clinicians to generate high-quality gametes,
      and to produce and identify gametes and embryos of maximum viability and
      implantation potential, which should contribute to improving take-home healthy
      baby rates.

PMID- 28756899
TI  - Effect of Routine Surveillance Imaging on the Outcomes of Patients With Classical
      Hodgkin Lymphoma After Autologous Hematopoietic Cell Transplantation.
AB  - BACKGROUND: Patients with relapsed and refractory classical Hodgkin lymphoma
      (cHL) are often treated with autologous hematopoietic cell transplantation (auto
      HCT). After auto-HCT, most transplant centers implement routine surveillance
      imaging to monitor for disease relapse; however, there is limited evidence to
      support this practice. PATIENTS AND METHODS: In this multicenter, retrospective
      study, we identified cHL patients (n = 128) who received auto-HCT, achieved
      complete remission (CR) after transplantation, and then were followed with
      routine surveillance imaging. Of these, 29 (23%) relapsed after day 100 after
      auto-HCT. Relapse was detected clinically in 14 patients and with routine
      surveillance imaging in 15 patients. RESULTS: When clinically detected relapse
      was compared with to radiographically detected relapse respectively, the median
      overall survival (2084 days [range, 225-4161] vs. 2737 days [range, 172-2750]; P
      = .51), the median time to relapse (247 days [range, 141-3974] vs. 814 days
      [range, 96-1682]; P = .30) and the median postrelapse survival (674 days [range,
      13-1883] vs. 1146 days [range, 4-2548]; P = .52) were not statistically
      different. In patients who never relapsed after auto-HCT, a median of 4 (range, 1
      25) surveillance imaging studies were performed over a median follow-up period of
      3.5 years. CONCLUSION: A minority of patients with cHL who achieve CR after auto
      HCT will ultimately relapse. Surveillance imaging detected approximately half of
      relapses; however, outcomes were similar for those whose relapse was detected
      using routine surveillance imaging versus detected clinically in between
      surveillance imaging studies. There appears to be limited utility for routine
      surveillance imaging in cHL patients who achieve CR after auto-HCT.

PMID- 28756900
TI  - Evaluation of Early Kidney Damage Caused by Brain Death Using Real-Time
      Ultrasound Elastography in a Bama Pig Model.
AB  - The aim of this study was to investigate the value of real-time tissue
      elastography (RTE) in the evaluation of early graft damage resulting from brain
      death. We performed RTE before and 0, 3, 6 and 9 h after brain death in a Bama
      pig model. Eleven RTE parameters were compared among time groups, and their
      correlations with electron microscopic findings were analyzed. Receiver operating
      characteristic curve analysis was used to find the RTE parameter cutoff values.
      The mean relative strain value within the region of interest (MEAN), standard
      deviation of the relative strain value within the region of interest (SD),
      percentage area of low strain within the region of interest (%AREA), complexity
      of low-strain area within the region of interest (COMP), kurtosis (KURT),
      skewness (SKEW), contrast (CONT) and entropy (ENT) and inverse difference moment
      (IDM) differed statistically significantly between groups (p < 0.05). Electron
      microscopy of kidney tissue revealed that irreversible damage gradually occurred
      with longer brain death duration and was marked at 9 h (p < 0.05). These findings
      correlated best with MEAN (r = 0.632, p < 0.05). Receiver operating
      characteristic curve analysis of RTE parameters identified a cutoff value of
      63.43 for MEAN for optimal diagnostic performance. RTE allows non-invasive,
      preliminary evaluation of early renal graft damage resulting from brain death.

PMID- 28756901
TI  - Respiratory Variation in Femoral Vein Diameter Has Moderate Accuracy as a Marker
      of Fluid Responsivity in Mechanically Ventilated Septic Shock Patients.
AB  - Ultrasound (US) is considered the first step in evaluation of patients with
      shock; respiratory variation of the inferior vena cava (inferior vena cava
      collapsibility [IVCc]) is an important measurement in this scenario that can be
      impaired by patient condition or technical skills. The main objective of this
      study was to evaluate if respiratory variation of the femoral vein (femoral vein
      collapsibility [FVc]), which is easier to visualize, can adequately predict fluid
      responsiveness in septic shock patients. Forty-five mechanically ventilated
      septic shock patients in a mixed clinical-surgical, 30-bed intensive care unit
      were enrolled in this study. All patients underwent assessments of FVc, IVCc and
      cardiac output using a portable US device. The passive leg raising test was used
      to evaluate fluid responsiveness. FVc presented an area under the receiver
      operating characteristic curve of 0.678 (95% confidence interval: 0.519-0.837, p
      = 0.044) with a cutoff point of 17%, yielding a sensitivity of 62% and
      specificity of 65% in predicting fluid responsiveness. IVCc had greater
      diagnostic accuracy compared with FVc, with an area under the receiver operating
      characteristic curve of 0.733 (95% confidence interval: 0.563-0.903, p = 0.024)
      and a cutoff point of 29%, yielding a sensitivity of 47% and specificity of 86%.
      In conclusion, FVc has moderate accuracy when employed as an indicator of fluid
      responsiveness in spontaneously mechanically ventilated septic shock patients.

PMID- 28756903
TI  - Defending academic and medical independence in Turkey.

PMID- 28756904
TI  - Bevacizumab in cervical cancer: a step forward for survival.

PMID- 28756902
TI  - Bevacizumab for advanced cervical cancer: final overall survival and adverse
      event analysis of a randomised, controlled, open-label, phase 3 trial
      (Gynecologic Oncology Group 240).
AB  - BACKGROUND: On Aug 14, 2014, the US Food and Drug Administration approved the
      antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the
      basis of improved overall survival (OS) after the second interim analysis (in
      2012) of 271 deaths in the Gynecologic Oncology Group (GOG) 240 trial. In this
      study, we report the prespecified final analysis of the primary objectives, OS
      and adverse events. METHODS: In this randomised, controlled, open-label, phase 3
      trial, we recruited patients with metastatic, persistent, or recurrent cervical
      carcinoma from 81 centres in the USA, Canada, and Spain. Inclusion criteria
      included a GOG performance status score of 0 or 1; adequate renal, hepatic, and
      bone marrow function; adequately anticoagulated thromboembolism; a urine protein
      to creatinine ratio of less than 1; and measurable disease. Patients who had
      received chemotherapy for recurrence and those with non-healing wounds or active
      bleeding conditions were ineligible. We randomly allocated patients 1:1:1:1
      (blocking used; block size of four) to intravenous chemotherapy of either
      cisplatin (50 mg/m2 on day 1 or 2) plus paclitaxel (135 mg/m2 or 175 mg/m2 on day
      1) or topotecan (0.75 mg/m2 on days 1-3) plus paclitaxel (175 mg/m2 on day 1)
      with or without intravenous bevacizumab (15 mg/kg on day 1) in 21 day cycles
      until disease progression, unacceptable toxic effects, voluntary withdrawal by
      the patient, or complete response. We stratified randomisation by GOG performance
      status (0 vs 1), previous radiosensitising platinum-based chemotherapy, and
      disease status (recurrent or persistent vs metastatic). We gave treatment open
      label. Primary outcomes were OS (analysed in the intention-to-treat population)
      and adverse events (analysed in all patients who received treatment and submitted
      adverse event information), assessed at the second interim and final analysis by
      the masked Data and Safety Monitoring Board. The cutoff for final analysis was
      450 patients with 346 deaths. This trial is registered with ClinicalTrials.gov,
      number NCT00803062. FINDINGS: Between April 6, 2009, and Jan 3, 2012, we enrolled
      452 patients (225 [50%] in the two chemotherapy-alone groups and 227 [50%] in the
      two chemotherapy plus bevacizumab groups). By March 7, 2014, 348 deaths had
      occurred, meeting the prespecified cutoff for final analysis. The chemotherapy
      plus bevacizumab groups continued to show significant improvement in OS compared
      with the chemotherapy-alone groups: 16.8 months in the chemotherapy plus
      bevacizumab groups versus 13.3 months in the chemotherapy-alone groups (hazard
      ratio 0.77 [95% CI 0.62-0.95]; p=0.007). Final OS among patients not receiving
      previous pelvic radiotherapy was 24.5 months versus 16.8 months (0.64 [0.37
      1.10]; p=0.11). Postprogression OS was not significantly different between the
      chemotherapy plus bevacizumab groups (8.4 months) and chemotherapy-alone groups
      (7.1 months; 0.83 [0.66-1.05]; p=0.06). Fistula (any grade) occurred in 32 (15%)
      of 220 patients in the chemotherapy plus bevacizumab groups (all previously
      irradiated) versus three (1%) of 220 in the chemotherapy-alone groups (all
      previously irradiated). Grade 3 fistula developed in 13 (6%) versus one (<1%). No
      fistulas resulted in surgical emergencies, sepsis, or death. INTERPRETATION: The
      benefit conferred by incorporation of bevacizumab is sustained with extended
      follow-up as evidenced by the overall survival curves remaining separated. After
      progression while receiving bevacizumab, we did not observe a negative rebound
      effect (ie, shorter survival after bevacizumab is stopped than after chemotherapy
      alone is stopped). These findings represent proof-of-concept of the efficacy and
      tolerability of antiangiogenesis therapy in advanced cervical cancer. FUNDING:
      National Cancer Institute.

PMID- 28756906
TI  - Universal screening of acute medical admissions for excess alcohol consumption:
      What's the misuse?

PMID- 28756905
TI  - Aspirin Versus Clopidogrel for Type 2 Diabetic Patients with First-Ever
      Noncardioembolic Acute Ischemic Stroke: Ten-Year Survival Data from the Athens
      Stroke Outcome Project.
AB  - BACKGROUND AND OBJECTIVE: Diabetes mellitus is associated with an increased risk
      of stroke and poor outcome following a stroke event. We assessed the impact of
      discharge treatment with aspirin versus clopidogrel on the 10-year survival of
      patients with type 2 diabetes after a first-ever noncardioembolic acute ischemic
      stroke (AIS). METHODS: This was a post hoc analysis of the Athens Stroke Outcome
      Project. Study outcomes included death, stroke recurrence, and a composite
      cardiovascular disease (CVD) end point (recurrent stroke, myocardial infarction,
      unstable angina, coronary revascularization, aortic aneurysm rupture, or sudden
      death). Kaplan-Meier survival curve and Cox regression analyses were performed.
      RESULTS: A total of 304 (93 women) diabetic patients receiving either aspirin (n
      = 197) or clopidogrel (n = 107) were studied. The 10-year survival was better in
      clopidogrel-treated patients than in aspirin-treated patients (19 deaths [17.7%]
      for clopidogrel versus 55 deaths [27.9%] for aspirin; log-rank test: 4.91, P =
      .027). Similarly, clopidogrel was associated with a favorable impact on recurrent
      stroke (12 events [11.2%] for clopidogrel versus 39 events [19.7%] for aspirin;
      log-rank test: 4.46, P = .035) and on the composite CVD end point (21 events
      [19.6%] for clopidogrel versus 54 events [27.4%] for aspirin; log-rank test:
      4.17, P = .041). In the multivariable analysis, the beneficial effect of
      clopidogrel over aspirin on both primary and secondary end points was independent
      of age, gender, the presence of CVD or CVD risk factors, and stroke severity.
      CONCLUSIONS: Our findings indicate a favorable effect of clopidogrel at discharge
      compared with aspirin in preventing death, recurrent stroke, and CVD events in
      diabetic patients with a first-ever noncardioembolic AIS.

PMID- 28756907
TI  - Universal screening for alcohol misuse in acute medical admissions is feasible
      and identifies patients at high risk of liver disease.
AB  - BACKGROUND & AIMS: Many people who die from alcohol related liver disease (ARLD)
      have a history of recurrent admissions to hospital, representing potential missed
      opportunities for intervention. Universal screening for alcohol misuse has been
      advocated but it is not known if this is achievable or effective at detecting
      individuals at high risk of ARLD. METHODS: We systematically screened all
      admissions to the Acute Medical Unit (AMU) of a large acute hospital using an
      electronic data capture system in real time. Patients at an increasing risk of
      alcohol harm were referred for either brief intervention (BI) or further
      assessment by an Alcohol Specialist Nursing Service (ASNS). Additional data were
      recorded on admission diagnoses, alcohol unit consumption, previous attendances,
      previous admissions, length of stay and mortality. RESULTS: Between July 2011 and
      March 2014, there were 53,165 admissions and 48,211 (90.68%) completed screening.
      Of these, 1,122 (2.3%) were classified as "increasing", and 1,921 (4.0%) as
      "high" risk of alcohol harm. High risk patients had more hospital admissions in
      the three previous years (average 4.74) than the low (3.00) and increasing (2.92)
      risk groups (p<0.001). The high risk patients also had more frequent emergency
      department (ED) attendances (7.68) than the lower (2.64) and increasing (3.81)
      groups (p<0.001 for both). A total of 1,396 (72.6%) of the high risk group were
      seen by the ASNS and 1,135 (81.2%) had an Alcohol Use Disorders Identification
      Test (AUDIT) score over 20 with 527 (37.8%) recording the maximum value of 40.
      Compared to the other groups, high risk patients had a distinct profile of
      admissions with the most common diagnoses being mental health disorders, gastro
      intestinal bleeding, poisoning and liver disease. CONCLUSIONS: Universal
      screening of admissions for alcohol misuse is feasible and identifies a cohort
      with frequent ED attendances, recurrent admissions and an elevated risk of ARLD.
      An additional group of patients at an increasing risk of alcohol harm can be
      identified in a range of common presentations. These patients can be targeted
      with interventions to reduce the burden of alcohol related harm. Lay summary:
      Many people who die from alcohol related liver disease (ARLD) have a recent
      history of recurrent admissions to hospital. These admissions may represent
      missed opportunities to intervene earlier and offer effective therapies for
      alcohol misuse. Unfortunately, we know that patients are often missed because
      medical staff may not routinely ask about alcohol consumption. In our study of
      over 50,000 admissions, we have demonstrated the feasibility of offering
      screening for alcohol misuse to all medical admissions to hospital and delivered
      this 24hours a day, 7days a week, with automatic referral to treatment services.
      We have shown that it is possible to identify those people who are at the highest
      risk of dependency, those who have attended the emergency department the most and
      those who are at an increased risk of ARLD. We hope this study will lead to
      improved detection and management of alcohol problems in acute hospitals.

PMID- 28756908
TI  - Assessing the impacts of bait collection on inter-tidal sediment and the
      associated macrofaunal and bird communities: The importance of appropriate
      spatial scales.
AB  - Bait collection is a multibillion dollar worldwide activity that is often managed
      ineffectively. For managers to understand the impacts on protected inter-tidal
      mudflats and waders at appropriate spatial scales macrofaunal surveys combined
      with video recordings of birds and bait collectors were undertaken at two UK
      sites. Dug sediment constituted approximately 8% of the surveyed area at both
      sites and is less muddy (lower organic content) than undug sediment. This may
      have significant implications for turbidity. Differences in the macrofaunal
      community between dug and undug areas if the same shore height is compared as
      well as changes in the dispersion of the community occurred at one site.
      Collection also induces a 'temporary loss of habitat' for some birds as bait
      collector numbers negatively correlate with wader and gull abundance. Bait
      collection changes the coherence and ecological structure of inter-tidal mudflats
      as well as directly affecting wading birds. However, as beta diversity increased
      we suggest that management at appropriate hectare/site scales could maximise
      biodiversity/function whilst still supporting collection.

PMID- 28756909
TI  - Gastroduodenal artery coiling to curb upper gastrointestinal bleeding.
AB  - BACKGROUND: Peptic ulcers in pediatric populations are uncommon and can present
      with upper gastrointestinal bleeding and shock on presentation. An endoscopy is
      done initially to identify bleeding source. However, definitive treatment is
      achieved with angiography. The use of coiling is effective in achieving
      hemorrhagic control in duodenal ulcers or gastric ulcers, particularly in adults.
      However, the use in pediatric populations is unknown. We present a case of peptic
      ulcer disease treated with a gastroduodenal artery coil in a pediatric patient
      that has never been reported in the literature. CASE PRESENTATION: A 15-year-old
      male with a five-year history of peptic ulcer disease was admitted with an upper
      gastrointestinal bleed. Angiographic imaging was done to isolate and locate the
      bleeding, and coil embolization of the gastroduodenal artery was performed. Coils
      eroded into intestinal lumen but bleeding was controlled. CONCLUSION: Peptic
      ulcers in pediatric populations are rare and complex in nature. Besides
      aggressive resuscitation and endoscopy, other methods to control bleeding such as
      coil embolization can be performed. Further investigations are needed to
      understand long-term effects of coil embolization in pediatric peptic ulcer
      patients. LEVEL OF EVIDENCE: 5/Case Report/.

PMID- 28756910
TI  - Macrophages and PMA-stimulated macrophage-like cells express the erythroid cell
      lineage adhesion molecule, ICAM-4: Implications for generation of erythrocytes in
      vitro.

PMID- 28756911
TI  - The Current Status of Molecular Xenomonitoring for Lymphatic Filariasis and
      Onchocerciasis.
AB  - The capacity of vector insect surveillance to provide estimates of pathogen
      prevalence and transmission potential has long been recognized within the global
      communities tasked with eliminating lymphatic filariasis (LF), the underlying
      cause of elephantiasis and hydrocele, and onchocerciasis (river blindness).
      Initially restricted to the practice of dissection, the potential of vector
      monitoring has grown due to the advent of molecular methods capable of increasing
      the sensitivity and throughput of testing. However, despite such advancement,
      operational research gaps remain. If insufficiently addressed, these gaps will
      reduce the utility of molecular xenomonitoring (MX) for onchocerciasis as
      elimination efforts expand into Africa. Similarly, such shortcomings will limit
      the programmatic usefulness of MX for LF, resulting in this technique's
      significant underutilization.

PMID- 28756912
TI  - A Community-Based Screening Program for Chagas Disease in the USA.
AB  - Chagas disease (CD) affects over 300 000 people in the USA, many with limited
      access to healthcare. Although early detection and treatment prevents life
      threatening complications, <1% of people with CD receive diagnosis, and routine
      screening is virtually nonexistent in the USA. We describe a program that led to
      an increase in CD screening in the Latin American-born population of Los Angeles.

PMID- 28756913
TI  - Kounis syndrome or allergic infarction: a relatively unknown entity.

PMID- 28756914
TI  - Hematological and splenic Doppler ultrasonographic changes in dogs sedated with
      acepromazine or xylazine.
AB  - OBJECTIVE: To evaluate the onset and duration of hematological changes and the
      use of Doppler ultrasound (spleen) in dogs sedated with acepromazine or xylazine.
      STUDY DESIGN: Clinical study. ANIMALS: A total of 24 mixed breed dogs aged 1-4
      years and weighing 15-25 kg. METHODS: Dogs were randomly distributed into two
      groups: acepromazine group (AG) which were administered acepromazine (0.05 mg kg
      1) intramuscularly and xylazine group (XG) administered xylazine (0.5 mg kg-1)
      intramuscularly. Sonographic evaluations (morphologic and hemodynamic splenic
      vascularization) and hematologic tests were performed before drug administration
      (baseline) and 5, 15, 30, 60, 120, 240, 360, 480 and 720 minutes after drug
      administration. RESULTS: A significant reduction occurred in erythrogram
      variables in AG at 15-720 minutes corresponding with a significant enlargement of
      the spleen. In XG, a significant reduction was observed in the erythrogram
      variables at 30-60 minutes without a significant enlargement of the spleen. Hilar
      diameter did not change over time in either group. Flow alterations were found
      only in the splenic artery in AG, with a decreased final diastolic velocity
      observed at 60-120 minutes. CONCLUSIONS: Administration of acepromazine resulted
      in decreased red blood cell count, hemoglobin, packed cell volume and an
      increased diameter of the spleen. Xylazine administration resulted in similar
      hematologic changes but of smaller magnitude and duration and without splenic
      changes. The absence of significant changes in the Doppler flow parameters of the
      splenic artery and vein and the hilar diameter suggests that the splenomegaly
      that was observed in AG was not due to splenic vasodilation. No splenic
      sequestration occurred after xylazine administration. CLINICAL RELEVANCE: The
      results indicate that acepromazine decreases the erythrocyte concentrations by
      splenic erythrocyte sequestration and concomitant splenomegaly. Xylazine can
      cause slight hematologic changes, but without splenic changes.

PMID- 28756915
TI  - In silico identification and characterization of common epitope-based peptide
      vaccine for Nipah and Hendra viruses.
AB  - OBJECTIVE: To explore a common B- and T-cell epitope-based vaccine that can
      elicit an immune response against encephalitis causing genus Henipaviruses,
      Hendra virus (HeV) and Nipah virus (NiV). METHODS: Membrane proteins F, G and M
      of HeV and NiV were retrieved from the protein database and subjected to
      different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell
      epitopes were then analyzed to predict their T-cell antigenic potentiality.
      Antigenic B- and T-cell epitopes that shared maximum identity with HeV and NiV
      were selected. Stability of the selected epitopes was predicted. Finally, the
      selected epitopes were subjected to molecular docking simulation with HLA-DR to
      confirm their antigenic potentiality in silico. RESULTS: One epitope from G
      proteins, one from M proteins and none from F proteins were selected based on
      their antigenic potentiality. The epitope from the G proteins was stable whereas
      that from M was unstable. The M-epitope was made stable by adding flanking
      dipeptides. The 15-mer G-epitope (VDPLRVQWRNNSVIS) showed at least 66% identity
      with all NiV and HeV G protein sequences, while the 15-mer M-epitope
      (GKLEFRRNNAIAFKG) with the dipeptide flanking residues showed 73% identity with
      all NiV and HeV M protein sequences available in the database. Molecular docking
      simulation with most frequent MHC class-II (MHC II) and class-I (MHC I) molecules
      showed that these epitopes could bind within HLA binding grooves to elicit an
      immune response. CONCLUSIONS: Data in our present study revealed the notion that
      the epitopes from G and M proteins might be the target for peptide-based subunit
      vaccine design against HeV and NiV. However, the biochemical analysis is
      necessary to experimentally validate the interaction of epitopes individually
      with the MHC molecules through elucidation of immunity induction.

PMID- 28756916
TI  - Effect of dietary supplementation with olive and sunflower oils on lipid profile
      and liver histology in rats fed high cholesterol diet.
AB  - OBJECTIVE: To compare the effects of high-monounsaturated (MUFA) and
      polyunsaturated fatty acids (PUFA) against the metabolic disorders elicited by a
      high-cholesterol diet (HC) in rats. METHODS: Using in vivo dietary manipulation,
      rats were fed with different diets containing 4% soybean oil (cholesterol free
      diet) and 1% HC containing 12% olive oil (HC + OO) enriched with MUFA and 12%
      sunflower oil (HC + SO) enriched with PUFA for 60 d. Serum lipid levels and
      hepatic steatosis were evaluated after the treatment period. RESULTS:
      Comparatively, rats treated with HC + OO diet experienced a decrease in the serum
      LDL-C, VLDL-C and CT levels compared to those fed with HC + SO diet (P < 0.05).
      Otherwise, HC + OO provoked significant microvesicular steatosis situated in the
      hepatic acinar zone 1. CONCLUSIONS: HC + OO diet has high absorption velocity in
      the acinar zone 1 of liver compared to the HC + SO diet. Based on this, the
      reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC
      + OO diet may have been caused by the delay in the FA release to the blood.

PMID- 28756917
TI  - Promising antileishmanial effectiveness of doxorubicin and Doxil against
      Leishmania major: An in vitro assay.
AB  - OBJECTIVE: To evaluate the effect of doxorubicin and its pegylated liposomal
      formulation (Doxil, Caelyx) on in vitro susceptibility of promastigote and
      amastigote stages of Leishmania major. METHODS: Throughout in vitro assays the
      IC50 was calculated in the promastigotes and amastigotes forms in J774 macrophage
      cell line. Also as cytotoxicity in J774 cell line macrophages. RESULTS:
      Doxorubicin and Doxil showed the same activity against promastigote form with
      IC50 values of 10.49 MUg/mL and 9.63 MUg/mL, respectively. Similarly, the
      amastigote stage was susceptible at concentration of at least 1 MUg/mL when
      compared to positive control (P < 0.0001). Also, cytotoxicity assay against
      macrophage revealed no toxicity on the host cells at IC50 concentrations.
      CONCLUSIONS: Our findings demonstrated the efficacy of both doxorubicin and its
      pegylated liposomal formulation on L. major at low concentrations. Further
      researches are needed for evaluating the safety of drugs in animal model
      particularly as topical formulation.

PMID- 28756918
TI  - Xanthine oxidase inhibitors from Archidendron clypearia (Jack.) I.C. Nielsen:
      Results from systematic screening of Vietnamese medicinal plants.
AB  - OBJECTIVE: To screen Vietnamese medicinal plants for xanthine oxidase (XO)
      inhibitory activity and to isolate XO inhibitor(s) from the most active plant.
      METHODS: The plants materials were extracted by methanol. The active plant
      materials were fractionated using different organic solvents, including n-hexane,
      ethyl acetate, and n-butanol. Bioassay-guided fractionation and column
      chromatography were used to isolate compounds. The compounds structures were
      elucidated by analysis of spectroscopic data, including IR, MS, and NMR. RESULTS:
      Three hundreds and eleven methanol extracts (CME) belonging to 301 Vietnamese
      herbs were screened for XO inhibitory activity. Among these plants, 57 extracts
      displayed XO inhibitory activity at 100 MUg/mL with inhibition rates of over 50%.
      The extracts of Archidendron clypearia (A. clypearia), Smilax poilanei, Linociera
      ramiflora and Passiflora foetida exhibited the greatest potency with IC50 values
      below 30 MUg/mL. Chemical study performed on the extract of A. clypearia resulted
      in the isolation of six compounds, including 1-octacosanol, docosenoic acid,
      daucosterol, methyl gallate, quercitrin and (-)-7-O-galloyltricetiflavan. The
      compound (-)-7-O-galloyltricetiflavan showed the most potent XO inhibitory
      activity with an IC50 value of 25.5 MUmol/L. CONCLUSIONS: From this
      investigation, four Vietnamese medicinal plants were identified to have XO
      inhibitory effects with IC50 values of the methanol extracts below 30 MUg/mL.
      Compound (-)-7-O- galloyltricetiflavan was identified as an XO inhibitor from A.
      clypearia with IC50 value of 25.5 MUmol/L.

PMID- 28756919
TI  - Protective effects of Balanites aegyptiaca extract, Melatonin and Ursodeoxycholic
      acid against hepatotoxicity induced by Methotrexate in male rats.
AB  - OBJECTIVE: To compare the degree of ameliorative effects of Melatonin (MEL),
      Ursodeoxycholic acid (UDCA) and Balanites aegyptiaca (BA) against hepatotoxicity
      induced by MTX for one month. METHODS: Eighty adult male rats (Sprague Dawely)
      weighing (190 +/- 10 g), were randomly divided into eight equal groups: Control,
      MTX, MEL, BA, UDCA, MTX + MEL, MTX + BA, MTX + UDCA. Liver function biomarker
      enzymes, liver tissue oxidative stress parameters, together with total
      antioxidant capacity and tumor necrosis factor (TNF-alpha) were determined.
      Histopathological and immunohistochemistry examinations for TNF-alpha were also
      done. RESULTS: MTX showed significant increase in alanine transaminase (ALT),
      aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl
      transferase (GGT), total and direct bilirubin, as well as TNF-alpha levels,
      oxidized glutathione (GSSG), malodialdehyde (MDA) and nitric oxide (NO). Whereas
      total protein, albumin, total antioxidant capacity, reduced glutathione (GSH),
      glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S
      transferase (GST), superoxide dismutase (SOD) and catalase (CAT) levels were
      significantly decreased in MTX treated group. These alterations were improved by
      MEL and BA treatment, whereas no improvement was noticed in UDCA treatment.
      CONCLUSIONS: BA may be as promising as MEL in the hepatoprotection against MTX
      toxicity through their antioxidant and radical scavenging activities. In
      addition, it is not recommended to co-administer UDCA with MTX as it enhanced
      inflammation and damage to the liver.

PMID- 28756920
TI  - Anticancer activity test of ethyl acetate extract of endophytic fungi isolated
      from soursop leaf (Annona muricata L.).
AB  - OBJECTIVE: To analyze anticancer activity of an ethyl acetate extract of
      endophytic fungi isolated from soursop leaf (Annona muricata L.). METHODS:
      Anticancer activity of fungal extracts was determined by observing its toxicity
      against MCF-7 (Michigan Cancer Foundation-7) cells in vitro by using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method. At an
      extract concentration of 100 MUg/mL, 4 isolates out of 12 showed high activity
      against the cancer cell growth. The four isolates were then selected for further
      IC50 determination, by measuring the inhibition of cancer cell proliferation at
      extract concentration of 25 MUg/mL, 50 MUg/mL, 100 MUg/mL, 200 MUg/mL and 400
      MUg/mL. RESULTS: Results showed that isolate Sir-G5 had the highest anticancer
      activity with an IC50 of 19.20 MUg/mL. The best isolates were screened again
      using a normal cell (Chang cells) to determine its toxicity against normal cells.
      Results indicated that the extracts do not affect the proliferation of normal
      cells. Molecular identification showed that the fungal isolate Sir-G5 has a close
      relationship with Phomopsis sp. CONCLUSIONS: The endophytic fungi isolated from
      soursop leaf has the potential to be used as a source of anticancer agents.

PMID- 28756921
TI  - Experimental study on the apoptosis of cervical cancer Hela cells induced by
      juglone through c-Jun N-terminal kinase/c-Jun pathway.
AB  - OBJECTIVE: To study the regulatory effect and molecular mechanism of juglone on
      apoptosis of cervical cancer Hela cells. METHODS: Cervical cancer Hela cells were
      cultured and treated with different dosages of juglone (10, 20, and 40 MUmol/L,
      respectively) and c-Jun N-terminal kinase (JNK) inhibitor SP600125 (10, 20, and
      40 MUmol/L, respectively). Then cellular proliferative activity and the
      expression of JNK/c-Jun pathway molecule and apoptotic molecule in the cells were
      detected. RESULTS: After 6, 12, 18 and 24 h of treatment, the value for
      proliferative activity of cells treated with juglone was significantly lower than
      that of control group (P < 0.05), and the anti-proliferative effect was more
      significant as the treatment period and juglone dosage increased (P < 0.05). The
      protein expressions of Bax, CytC, Fas, FasL, Caspase-3, p-JNK and p-c-Jun in
      cells treated with juglone were significantly higher than those of control group
      (P < 0.05), and the protein expressions of Bax, CytC, Fas, FasL, Caspase-3, p-JNK
      and p-c-Jun increased more remarkably as the juglone dosage increased (P < 0.05).
      In cells treated with 40 MUmol/L juglone and SP600125, the protein expressions of
      Bax, CytC, Fas, FasL and Caspase-3 were significantly lower than those of cells
      treated with 40 MUmol/L juglone (P < 0.05), and the protein expressions of Bax,
      CytC, Fas, FasL and Caspase-3 reduced more remarkably as the SP600125 dosage
      increased (P < 0.05). CONCLUSION: Juglone can increase the expression of
      apoptotic molecules in mitochondrial pathway and death receptor pathway by
      activating JNK/c-Jun pathway, thus inducing apoptosis of cervical cancer cells.

PMID- 28756922
TI  - In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melegueta
      and Denniettia tripetala extracts.
AB  - OBJECTIVE: To evaluate the in vitro and in vivo inhibitory effects of two
      commonly used herbs, Aframomum melegueta (A. melengueta) and Dennettia tripetala
      (D. tripetala) on CYP 3A enzymes. METHODS: In vitro inhibition of the enzymes
      were assessed with microsomes extracted from female albino rats using
      erythromycin-N-demethylation assay (EMND) method while their in vivo effects were
      measured by estimating simvastatin plasma concentrations in rats. Pharmacokinetic
      parameters were determined using non-compartmental analysis as implemented in
      WinNonlin pharmacokinetic program. RESULTS: EMND assay with intestinal microsomes
      indicated that aqueous extracts of D. tripetala and A. melengueta significantly
      (P < 0.05) inhibited intestinal CYP 3A activity at both 50 MUg and 100 MUg
      concentrations. Petroleum ether extract of D. tripetala and ethanol extracts of
      A. melengueta inhibited intestinal CYP3A activity at 100 MUg but not at 50 MUg
      concentrations. All the extracts showed an in vitro dose dependent CYP 3A
      inhibition with liver microsomes. In vivo analysis showed that pre-treatment with
      the extracts enhanced systemic absorption of simvastatin with reductions in
      metabolizing enzymes activity as indicated in significant increases in maximal
      concentration, area under curve, area under moment curve and mean resident time
      of simvastatin (P < 0.05). CONCLUSIONS: Herbal preparations containing these
      plants' extracts should be used with caution especially in patients on CYP450 3A
      substrate medications.

PMID- 28756923
TI  - Atractylenolide I protects against lipopolysaccharide-induced disseminated
      intravascular coagulation by anti-inflammatory and anticoagulation effect.
AB  - OBJECTIVE: To investigate whether atractylenolide I (ATL-I) has protective effect
      on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC)
      in vivo and in vitro, and explore whether NF-kappaB signaling pathway is involved
      in ATL-I treatment. METHODS: New Zealand white rabbits were injected with LPS
      through marginal ear vein over a period of 6 h at a rate of 600 MUg/kg (10 mL/h).
      Similarly, in the treatment groups, 1.0, 2.0, or 5.0 mg/kg ATL-I were given. Both
      survival rate and organ function were tested, including the level of alanine
      aminotransferase (ALT), blood urine nitrogen (BUN), and TNF-alpha were examined
      by ELISA. Also hemostatic and fibrinolytic parameters in serum were measured. RAW
      264.7 macrophage cells were administered with control, LPS, LPS + ATL-I and ATL-I
      alone, and TNF-alpha, phosphorylation (P)-IkappaBalpha, phosphorylation (P)-NF
      kappaB (P65) and NF-kappaB (P65) were determined by Western blot. RESULTS: The
      administration of LPS resulted in 73.3% mortality rate, and the increase of serum
      TNF-alpha, BUN and ALT levels. When ATL-I treatment significantly increased the
      survival rate of LPS-induced DIC model, also improved the function of blood
      coagulation. And protein analysis indicated that ATL-I remarkably protected liver
      and renal as decreasing TNF-alpha expression. In vitro, ATL-I obviously decreased
      LPS-induced TNF-alpha production and the expression of P-NF-kappaB (P65), with
      the decrease of P-IkappaBalpha. CONCLUSIONS: ATL-I has protective effect on LPS
      induced DIC, which can elevate the survival rate, reduce organ damage, improve
      the function of blood coagulation and suppress TNF-alpha expression by inhibiting
      the activation of NF-kappaB signaling pathway.

PMID- 28756924
TI  - Antioxidant and hepatoprotective potentials of novel endophytic fungus
      Achaetomium sp., from Euphorbia hirta.
AB  - OBJECTIVE: To isolate, identify and evaluate the antioxidant, antimicrobial,
      hepatoprotective potentials, total phenolic content, flavonoid content, tannin
      content of ethyl acetate extract of endophytic fungus Achaetomium sp., isolated
      from Euphorbia hirta. METHODS: Hepatoprotectivity of ethyl acetate extract of
      Achaetomium sp., was evaluated by CCl4 induced toxicity in HepG2 cells and
      subsequently analysed for cell viability using MTT assay. It also demonstrates
      antioxidant and antimicrobial potentials by DPPH radical scavenging assay and
      well diffusion assay respectively. Quantification of total phenolic content,
      tannin content and flavonoid content were assessed by spectroscopic methods.
      RESULTS: Phenols, flavonoids and tannins were the phytochemicals present in ethyl
      acetate extract of Achaetomium sp., with rich phenolic content exhibited potent
      hepatoprotective, antimicrobial and antioxidant activities. The hepatoprotective
      activity was recorded as of 72.13% +/- 2.948% of cell viability at a
      concentration of 150 MUg/mL, whereas the standard silymarin showed 93.260% +/-
      0.784%. It was observed to be dose dependent, when CCl4 exposed HepG2 cells were
      treated with different concentrations of ethyl acetate extract. Antibacterial
      activity showed significant inhibition against Staphylococcus aureus, Pseudomonas
      aeroginosa, and Klebsiella pneumoniae. The antioxidant activity ranged from
      66.890% +/- 1.385% to 87.340% +/- 0.289% with (44.02 +/- 1.57) MUg of total
      phenolics, (54.54 +/- 1.82) MUg of flavonoid content and (18.790 +/- 1.018) MUg
      of tannin content. Ascorbic acid, BHT (butylated hydroxyl toluene) Gallic acid
      and Pyrogallol were used as standards which showed 98.370% +/- 0.763%; 97.080% +/
      0.636%; 94.890% +/- 1.103% and 96.980% +/- 0.098% reducing potential
      respectively. CONCLUSIONS: The results reveal that the metabolites produced by
      endophytic fungi isolated from Euphorbia hirta could be novel natural products
      that could lead to new drug discovery.

PMID- 28756925
TI  - Intervention effect and mechanism of curcumin in chronic urinary tract infection
      in rats.
AB  - OBJECTIVE: To analyze the invention effect of curcumin on chronic urinary tract
      infection in rats and explore its possible mechanism of action. METHODS: The
      experimental animals were randomly divided into three groups, normal, model and
      curcumin group. Chronic urinary tract infection models were built for model group
      and curcumin group by injecting coliform fluid into the cavity of bladder. From
      the first day of modeling, rats in the curcumin group were injected with 150
      mg/kg curcumin, while rats in normal group and model group were given no other
      treatment. The treatment lasted for 14 d. The white blood cell counts in blood
      and urine, bacterial colony count in urine and renal tubular functional indexes
      of rats in all groups at day 1, 7, and 14 after treatment were detected. Urine
      beta2-microglobulin (beta2-MG), urinary N-acetyl-beta-D glucosaminidase (NAG)
      levels were used to detected the inflammatory cytokines in serum after treatment
      including the contents of IL-6, IL-8, IL-10 and monocyte chemoattractant protein
      1 (MCP-1), and real-time PCR was employed to determine the expression of mRNA of
      toll-like receptor 2 (TLR-2) and TLR-4 in renal tissues and bladder tissues of
      all groups after treatment. RESULTS: The white blood cell counts at day 1 and 7
      after treatment in rats of model group and curcumin group were significantly
      higher than those of normal group at the same time points, while the white blood
      cell counts of the curcumin group were significantly lower than those of model
      group (P < 0.05). The urine white blood cell counts in rats of model group at day
      1, 7 and 14 were all significantly higher than those of normal group at the same
      time points; those in the curcumin group were significantly lower than those of
      the model group at day 1, 7 and 14 at the same time points (P < 0.05). The
      bacterial colony counts of urine in rats of model group and curcumin group at day
      1, 7 and 14 were all significantly higher than those of normal group at the same
      time points, while the counts of curcumin group were significantly lower than
      those of model group at the same time points (P < 0.05). Levels of urine beta2
      MG, NAG, IL-6, IL-8, IL-10, MCP-1 and expression of TLR2 mRNA and TLR4 mRNA in
      renal and bladder tissues in rats of model group were significantly higher than
      those of the normal group, while these variables of the curcumin group were
      significantly higher than those of the normal group but lower than those of model
      group (P < 0.05). CONCLUSIONS: Curcumin can significantly improve the symptoms of
      chronic urinary tract infections, protect renal tubular function, and also
      decline inflammatory responses by influencing the expressions of TLR2 mRNA and
      TLR4 mRNA so as to exert its curative effect on chronic urinary tract infections.

PMID- 28756926
TI  - Comparison of phenolic components and biological activities of two Centaurea sp.
      obtained by three extraction techniques.
AB  - OBJECTIVE: The present study aimed to compare the polyphenol content, total
      phenolic, total flavonoid, antioxidant and antimicrobial activity of the extracts
      obtained from Centaurea amaena Boiss. & Balansa and Centaurea aksoyi Hamzaoglu &
      Budak. METHODS: Both species were subjected to maceration, Soxhlet and
      ultrasonication extractions with methanol in order to macerated (ME), Soxhlet
      (SE) and ultrasonicated (UE) extracts. Their phenolic profiles were qualitatively
      examined by LC-MS. Their antioxidant activities were determined by
      phosphomolybdenum, beta-carotene bleaching and DPPH assays. Agar diffusion and
      broth dilution methods were carried out to find the antimicrobial activity of
      these extracts against fifteen microorganisms. RESULTS: Quercetin, quercetin-3
      beta-D-glucoside and protocatechuic acid were the main components of the both
      extracts obtained by Soxhlet extraction. The highest phenolic and flavonoid
      contents were found in the UE for both species. All the extracts exhibited good
      total antioxidant and DPPH radical scavenging activity. UE obtained from C.
      amaena showed the highest antioxidant activity with the highest phenolic and
      flavonoid contents. The antibacterial activity of UE obtained from C. amaena was
      better than other extracts and antibacterial activity of C. amaena was also
      better than C. aksoyi. DISCUSSION: This study confirms that ultrasonic extraction
      may be an ideal, simple and rapid method to obtain polyphenol-rich extracts have
      antioxidant as well as antibacterial activity from both Centaurea species
      especially from C. amaena.

PMID- 28756927
TI  - The relationship between fractional anisotropy value and tumor microarchitecture
      in late-stage rat glioma.
AB  - OBJECTIVE: To explore the magnetic resonance diffusion tensor imaging (MR-DTI)
      features of in the late stage of Wistar rat C6 brain glioma, and the relationship
      between fractional anisotropy value and tumor microarchitecture. METHODS: The
      concentration of more than 1.0 * 106/10 MUL glioma cells and complete medium were
      injected stereotactically into the right caudate nucleus of the experimental
      group (n = 35) and control group (n = 10), respectively. Conventional MRI, DTI,
      and enhanced T1WI scans were Performed using the GE Signa HD * 3.0T MRI scanner
      about 3-4 weeks after implantation for the rats. Postprocessing was done using
      the DTI specific software Function Tool to gain FA image. Many ROIs were drawn
      avoiding hemorrhage, necrosis areas in tumor parenchyma, the value of FA was
      recorded. Each surviving rat brain was examined histologically using HE and
      immunohistochemical staining for VEGF and CD34. Pearson correlation analysis was
      used to determine the relationships between FA values and VEGF, MVD, cell
      density, respectively. RESULTS: A total of 35 tumor-bearing rats were confirmed
      the tumor formation by the subsequent MRI and pathological examination. The mean
      FA values of the tumor and the contralateral brain tissue were 0.17 +/- 0.03 and
      0.31 +/- 0.05 respectively, and the difference was statistically significant (t =
      12.80, P < 0.05). The mean FA value of grade III glioma (n = 12) was 0.16 +/-
      0.03, and the average FA value of grade IV glioma (n = 23) was about 0.18 +/-
      0.04. There was no significant difference between the two groups (t = 1.92, P >
      0.05). FA value in the late stage of Wistar rat C6 brain glioma has significant
      positive correlation to VEGF, MVD, cell density. The correlation coefficients
      between FA and VEGF, MVD, and cell density were 0.67, 0.65 and 0.71 (P < 0.05),
      respectively. CONCLUSIONS: The FA value of rat glioma tumor in the late stage can
      preoperatively provide an accurate, reliable and noninvasive imaging monitoring
      method to evaluate the microstructure of glioma (cell density, the extent of
      angiogenesis, fiber bundle integrity and tumor cell infiltration and so on),
      predict the biological behavior of the tumor and make out surgical plan.

PMID- 28756928
TI  - Doubled dosage of sofosbuvir is expected for inhibiting Zika virus infection.
AB  - Sofosbuvir is a new antiviral drug that has been recommended for management of
      hepatitis C virus (HCV) for a few years. New researches support that sofosbuvir
      might be useful for the management of Zika virus infection. Based on the
      pharmacological activity, inhibiting the HCV RNA-dependent RNA polymerase (RdRp
      or NS5 protein), sofosbuvir is proposed for its effectiveness against Zika virus
      infection. Here, the authors used a mathematical modelling theoretical approach
      to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection.
      Based on the modeling study, if sofosbuvir is assigned for management of Zika
      virus infection, doubled dosage of the present dosage for hepatitis C management
      is recommended.

PMID- 28756929
TI  - Exploring on the elderly health management model in tropic area.
AB  - In this article, based on the characteristics of tropical area, we analyze the
      beneficial and the disadvantage of tropical area to human health, points out the
      existing problems in elderly health management pattern in the tropics area,
      accordingly we discuss how to establish tropical characterized elderly health
      management, and put forward constructive suggestions.

PMID- 28756930
TI  - Retraction notice to: Effect of transplantation of BMMSCs on pathological change
      of gastric precancerous lesions of rats [Asian Pac J Trop Med 8(12) (2015) 1060
      1063].

PMID- 28756931
TI  - Retraction notice to: Effect of thioredoxin-interacting protein on Wnt/beta
      catenin signaling pathway and diabetic myocardial infarction [Asian Pac J Trop
      Med 8(11) (2015) 976-982].

PMID- 28756932
TI  - Fear of childbirth and depressive symptoms among postnatal women: A cross
      sectional survey from Chhattisgarh, India.
AB  - BACKGROUND: Prevalence rates of Fear of Birth and postnatal depressive symptoms
      have not been explored in Chhattisgarh, India. OBJECTIVE: To validate Hindi Wijma
      Delivery Experience Questionnaire and to study the prevalence of Fear of Birth
      and depressive symptoms among postnatal women. METHODS: A cross-sectional survey
      at seventeen public health facilities in two districts of Chhattisgarh, India
      among postnatal women who gave birth vaginally or through C-section to a live
      neonate. Participants were recruited through consecutive sampling based on health
      facility records of daily births. Data were collected through one-to-one
      interviews using the Wijma Delivery Experience Questionnaire Version B and the
      Edinburgh Postnatal Depression Scale. Non-parametric associations and linear
      regression data analyses were performed. RESULTS: The Hindi Wijma Delivery
      Experience Questionnaire Version B had reliable psychometric properties. The
      prevalence of Fear of Birth and depressive symptoms among postnatal women were
      13.1% and 17.1%, respectively, and their presence had a strong association
      (p<0.001). Regression analyses revealed that, among women having vaginal births:
      coming for institutional births due to health professionals' advice, giving birth
      in a district hospital and having postnatal depressive symptoms were associated
      with presence of FoB; while depressive symptoms were associated with having FoB,
      perineal suturing without pain relief, and giving birth to a low birth-weight
      neonate in a district hospital. CONCLUSION: The prevalence of Fear of Birth and
      depressive symptoms is influenced by pain management during childbirth and care
      processes between women and providers. These care practices should be improved
      for better mental health outcomes among postnatal women.

PMID- 28756933
TI  - Pericardial Herniation of Small Bowel Post Minimally Invasive Hybrid Maze of
      Atrial Fibrillation.
AB  - BACKGROUND: Herniation of intraabdominal contents into the pericardial cavity is
      exceptionally rare, and when seen, it is most often the result of trauma,
      postsurgical complication, or genetic defect. There have been only a few case
      reports describing spontaneous bowel herniation into the pericardium in minimally
      invasive cardiac procedures like cardiac ablation, pacemaker placement, and
      minimally invasive coronary artery bypass graft. CASE REPORT: We report the case
      of a 65-year-old man who presented to an urgent care center complaining of
      abdominal and chest pain. This patient had recently undergone a laparoscopic
      hybrid maze procedure and ultimately had an incarcerated loop of small bowel
      herniate into the pericardial sac. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
      THIS?: We present this case to increase awareness among emergency physicians of
      the diagnosis of a pericardial hernia in patients presenting with
      gastrointestinal or cardiorespiratory symptoms after surgical procedures
      involving the diaphragm.

PMID- 28756935
TI  - Corrigendum to "Pre- and Poststimulation Study on the Phonatory Aerodynamic
      System on Participants with Dysphonia" [Journal of Voice 31 (2017) 254.e1
      254.e9].

PMID- 28756934
TI  - Postoperative Anticholinergic Poisoning: Concealed Complications of a Commonly
      Used Medication.
AB  - BACKGROUND: Scopolamine is a potent anticholinergic compound used commonly for
      the prevention of postoperative nausea and vomiting. Scopolamine can cause
      atypical anticholinergic syndromes due to its prominent central antimuscarinic
      effects. CASE REPORT: A 47-year-old female presented to the emergency department
      (ED) 20 h after hospital discharge for a right-knee meniscectomy, with altered
      mental status (AMS) and dystonic extremity movements that began 12 h after her
      procedure. Her vital signs were normal and physical examination revealed
      mydriasis, visual hallucinations, hyperreflexia, and dystonic movements.
      Laboratory data, lumbar puncture, and computed tomography were unrevealing. The
      sustained AMS prompted a re-evaluation that revealed urinary overflow with 500 mL
      of retained urine discovered on ultrasound and a scopolamine patch hidden behind
      her ear. Her mental status improved shortly after patch removal and
      physostigmine, with complete resolution after 24 h with discharge diagnosis of
      scopolamine-induced anticholinergic toxicity. WHY SHOULD AN EMERGENCY PHYSICIAN
      BE AWARE OF THIS?: Although therapeutically dosed scopolamine transdermal patches
      rarely cause complications, incomplete toxidromes can be insidiously common in
      polypharmacy settings. Providers should thoroughly evaluate the skin of
      intoxicated patients for additional adherent medications that may result in a
      delay in ED diagnosis and curative therapies. Our case, as well as rare case
      reports of therapeutic scopolamine-induced anticholinergic toxicity, demonstrates
      that peripheral anticholinergic effects, such as tachycardia, dry mucous
      membranes, and hyperpyrexia are often not present, and incremental doses of
      physostigmine may be required to reverse scopolamine's long duration of action.
      This further complicates identification of the anticholinergic toxidrome and
      diagnosis.

PMID- 28756936
TI  - Detecting Laryngopharyngeal Reflux by Immunohistochemistry of Pepsin in the
      Biopsies of Vocal Fold Leukoplakia.
AB  - Laryngopharyngeal reflux (LPR) may contribute to the development of laryngeal
      diseases including vocal fold leukoplakia. Clinical methods of determining LPR
      are limited. Pepsin, as an exogenous protein, is considered as a biomarker of
      LPR. The aim of the current study was, therefore, to detect pepsin by
      immunohistochemistry in the biopsies from patients with vocal fold leukoplakia,
      and by which, to determine the potential association of LPR and vocal
      leukoplakia. A total of 26 biopsies from patients with vocal fold leukoplakia
      were examined in comparison with 20 vocal fold biopsies from control subjects. We
      found that 2 out of 26 patients (7.7%) were strongly positive, 4 of the 26
      (15.4%) patients were positive, 11 of the 26 (42.3%) patients were weakly
      positive, and 9 of the 26 (34.6%) were negative staining for pepsin. In contrast,
      only 4 of the 20 (20.0%) control subjects were weakly positive and the rest (16;
      80.0%) were negative staining for pepsin. There was significant difference
      between the two groups in terms of positivity of pepsin staining (chi2 = 24.181,
      P <0.001). These findings suggest that pepsin immunohistochemical staining could
      be a biomarker of LPR and that LPR may be a risk factor for the development of
      vocal fold leukoplakia.

PMID- 28756937
TI  - Short-pulse neodymium:yttrium-aluminium garnet (Nd:YAG 1064nm) laser irradiation
      photobiomodulates mitochondria activity and cellular multiplication of Paramecium
      primaurelia (Protozoa).
AB  - Few studies exist to explore the potential photobiomodulation (PBM) effect of
      neodymium:yttrium-aluminium garnet (Nd:YAG) laser irradiation using a flat-top
      handpiece delivery system. In this study, we explored the photobiomodulation
      effect of that laser, on Paramecium primaurelia. The parameters for the different
      study groups were: 0.50W, 10Hz, 100msp, 30J/cm2; 0.75W, 10Hz, 100msp, 45J/cm2;
      1.00W, 10Hz, 100msp, 60J/cm2; 1.25W, 10Hz, 100msp, 75J/cm2 and 1.50W, 10Hz,
      100msp, 90J/cm2. Our results suggest that only the parameter 0.5W, 10Hz, 100msp,
      30J/cm2 positively photobiomodulates the Paramecium cells inducing an increment
      in oxygen consumption, endogenous ATP synthesis and fission rate rhythm. Applying
      the laser energy with parameters of 1.25W, 10Hz, 100msp, 75J/cm2 and 1.50W, 10Hz,
      100msp, 90J/cm2, induce adverse effect on the Paramecium cells, which protect
      themselves through the increase in Heat Shock Protein-70 (HSP70). The data
      presented in our work support our assumption that, when using appropriate
      parameters of irradiation, the 1064nm Nd:YAG laser with flat-top handpiece could
      be a valuable aid for effective clinical application of PBM.

PMID- 28756938
TI  - Isolation and molecular characterization of Acanthamoeba from patients with
      keratitis in Spain.
AB  - In order to improve our knowledge on the epidemiology of amoebic keratitis, as
      well as the identification of Acanthamoeba isolates, we have isolated
      Acanthamoeba spp. from five symptomatic patients in Spain in the present study.
      All isolates were grown in axenic liquid medium, with only one exception. The
      morphology of these isolates were characterized by optical and scanning electron
      microscopy. Their structural features corresponded to those of amphizoic amoebae
      (namely Acanthamoeba spp.). The molecular characterization of the five
      Acanthamoeba isolates yielded six sequences. Almost complete 18S rRNA gene
      sequences (>2000bp) were obtained from three isolates and partial sequences
      (~1500bp) from the other two. A robust phylogenetic analysis based on the almost
      complete 18S rRNA sequence showed that four isolates belonged to the T4 genotype
      and the other one to the T3 genotype. However, all isolates were identified as T4
      genotype using the ASA.S1 fragment. As previously suggested by other researchers,
      only a robust phylogenetic approach may be helpful in identifying Acanthamoeba
      genotypes. In addition, new data on the phylogenetic relationships among the
      Acanthamoeba genotypes is provided and discussed.

PMID- 28756939
TI  - Bacteriology of peritonsillar abscess: the changing trend and predisposing
      factors.
AB  - INTRODUCTION: Peritonsillar abscess is the most common deep neck infection. The
      infectious microorganism may be different according to clinical factors.
      OBJECTIVE: To identify the major causative pathogen of peritonsillar abscess and
      investigate the relationship between the causative pathogen, host clinical
      factors, and hospitalization duration. METHODS: This retrospective study included
      415 hospitalized patients diagnosed with peritonsillar abscess who were admitted
      to a tertiary medical center from June 1990 to June 2013. We collected data by
      chart review and analyzed variables such as demographic characteristics,
      underlying systemic disease, smoking, alcoholism, betel nut chewing,
      bacteriology, and hospitalization duration. RESULTS: A total of 168 patients had
      positive results for pathogen isolation. Streptococcus viridans (28.57%) and
      Klebsiella pneumoniae (23.21%) were the most common microorganisms identified
      through pus culturing. The isolation rate of anaerobes increased to 49.35% in the
      recent 6 years (p=0.048). Common anaerobes were Prevotella and Fusobacterium spp.
      The identification of K. pneumoniae increased among elderly patients (age>65
      years) with an odds ratio (OR) of 2.76 (p=0.03), and decreased in the hot season
      (mean temperature>26 degrees C) (OR=0.49, p=0.04). No specific microorganism was
      associated with prolonged hospital stay. CONCLUSION: The most common pathogen
      identified through pus culturing was S. viridans, followed by K. pneumoniae. The
      identification of anaerobes was shown to increase in recent years. The
      antibiotics initially selected should be effective against both aerobes and
      anaerobes. Bacterial identification may be associated with host clinical factors
      and environmental factors.

PMID- 28756940
TI  - Developing a scale of domains of negative consequences of chronic heroin use.
AB  - BACKGROUND: Chronic use of heroin typically leads to numerous negative life
      consequences and serious clinical impairment. Increased negative consequences can
      result in poor treatment outcomes as well as adverse health effects and impaired
      social functioning. Certain risk factors, including early substance use
      initiation, concurrent use of other illicit substances, and injection drug use
      are associated with an increase in negative consequences. This study examined
      whether there are unique domains of heroin consequences and, if so, whether these
      domains are related to specific substance use characteristics. METHODS: Data
      regarding substance use characteristics were collected from 370 non-treatment
      seeking, heroin-using, 18 to 55year-old participants from the Detroit
      metropolitan area. Principal component analysis (PCA) was used to analyze the
      factor structure of 21 negative heroin consequence items. RESULTS: PCA
      demonstrated that heroin consequences could be divided into 5 unique domains.
      These unique domains were related to specific substance use characteristics and
      heroin consequence domains. Injection heroin use was significantly associated
      with increased Factor 1 consequences (primarily acute medical problems) but not
      with consequences in other domains. Certain substance use characteristics, such
      as injection status and earlier onset of marijuana use, were associated with
      increased consequences in specific domains. CONCLUSIONS: These findings support
      the existence of unique domains of negative consequences, and indicate that some
      risk factors (e.g. injection use) may be specific to these domains. Potential
      tailored-treatment strategies aimed at improving treatment engagement and
      reducing harm for heroin use based on person-specific risks and negative
      consequences are discussed.

PMID- 28756941
TI  - Peripheral lipid oxidative stress markers are related to vascular risk factors
      and subcortical small vessel disease.
AB  - Subcortical white matter hyperintensities (WMH), presumed to indicate small
      vessel ischemic vascular disease, are found commonly in elderly individuals with
      and without Alzheimer's disease (AD). Oxidative stress may instigate or
      accelerate the development of vascular disease, and oxidative stress markers are
      elevated in AD. Here, we assess independent relationships between three serum
      lipid peroxidation markers (lipid hydroperoxides [LPH], 8-isoprostane, and 4
      hydroxynonenal) and the presence of extensive subcortical WMH and/or AD. Patients
      were recruited from memory and stroke prevention clinics into four groups:
      minimal WMH, extensive WMH, AD with minimal WMH, and AD with extensive WMH.
      Extensive WMH, but not AD, was associated with higher serum concentrations of 8
      isoprostane and LPH. Peripheral LPH concentrations mediated the effect of
      hypertension on deep, but not periventricular, WMH volumes. 4-hydroxynonenal was
      associated with hyperlipidemia and cerebral microbleeds, but not with extensive
      WMH or AD. We conclude that lipid peroxidation mediates hypertensive injury to
      the deep subcortical white matter and that peripheral blood lipid peroxidation
      markers indicate subcortical small vessel disease regardless of an AD diagnosis.

PMID- 28756943
TI  - Evaluation of stress response using psychological, biological, and
      electrophysiological markers during immersive simulation of life threatening
      events in multidisciplinary teams.
AB  - Stress might impair clinical performance in real life and in simulation-based
      education (SBE). Subjective or objective measures can be used to assess stress
      during SBE. This monocentric study aimed to evaluate the effects of simulation of
      life-threatening events on measurements of various stress parameters
      (psychological, biological, and electrophysiological parameters) in
      multidisciplinary teams (MDTs) during SBE. The effect of gender and status of
      participants on stress response was also investigated. Twelve emergency MDTs of 4
      individuals were recruited for an immersive simulation session. Stress was
      assessed by: (1) self-reported stress; (2) Holter analysis, including heart rate
      and heart rate variability in the temporal and spectral domain (autonomic nervous
      system); (3) salivary cortisol (hypothalamic pituitary adrenal axis). Forty-eight
      participants (54.2% men, <7years of experience) were included. Measures were
      performed at baseline (T0), after simulation (T1), after debriefing (T2), and
      30min after debriefing (T3). There was an increase in stress level at T1
      (p<0.001) and a decrease at T2 (p<0.001). However, the variations of stress
      parameters induced by simulation (T0-T1 difference and T1-T2 difference)
      estimated by the three approaches were not correlated, while, as expected, Holter
      parameters were well-correlated to each other. Immersive SBE produced a change of
      stress level in all MDT members with no evidence for status effect but with
      gender difference. None developed a PTSD. These results support the hypothesis of
      a complementarity of the stress paths (collective reaction with increased stress
      level during simulation and a decrease during debriefing) but with relative
      independence of these paths (lack of correlation to each other). This study also
      suggests that because of the lack of correlation, stress response should be
      assessed by a combination of psychological, biological and electrophysiological
      parameters.

PMID- 28756942
TI  - Identifying incipient dementia individuals using machine learning and amyloid
      imaging.
AB  - Identifying individuals destined to develop Alzheimer's dementia within time
      frames acceptable for clinical trials constitutes an important challenge to
      design studies to test emerging disease-modifying therapies. Although amyloid
      beta protein is the core pathologic feature of Alzheimer's disease, biomarkers of
      neuronal degeneration are the only ones believed to provide satisfactory
      predictions of clinical progression within short time frames. Here, we propose a
      machine learning-based probabilistic method designed to assess the progression to
      dementia within 24 months, based on the regional information from a single
      amyloid positron emission tomography scan. Importantly, the proposed method was
      designed to overcome the inherent adverse imbalance proportions between stable
      and progressive mild cognitive impairment individuals within a short observation
      period. The novel algorithm obtained an accuracy of 84% and an under-receiver
      operating characteristic curve of 0.91, outperforming the existing algorithms
      using the same biomarker measures and previous studies using multiple biomarker
      modalities. With its high accuracy, this algorithm has immediate applications for
      population enrichment in clinical trials designed to test disease-modifying
      therapies aiming to mitigate the progression to Alzheimer's disease dementia.

PMID- 28756944
TI  - Laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: Long
      term oncologic outcomes after standard resection.
AB  - BACKGROUND: Surgical resection is the only curative option in patients with
      pancreatic ductal adenocarcinoma. Little is known about the oncologic outcomes of
      laparoscopic distal pancreatectomy. This bi-institutional study aimed to examine
      the long-term oncologic results of standard laparoscopic distal pancreatectomy in
      a large cohort of patients with pancreatic ductal adenocarcinoma. METHODS: From
      January 2002 to March 2016, 207 patients underwent standard laparoscopic distal
      pancreatectomy for pancreatic ductal adenocarcinoma at Oslo University Hospital
      Rikshospitalet (Oslo, Norway) and Asan Medical Centre (Seoul, Republic of Korea).
      After the exclusion criteria were applied (distant metastases at operation,
      conversion to an open operation, loss to follow-up), 186 patients were eligible
      for the analysis. Perioperative and oncologic variables were analyzed for
      association with recurrence and survival. RESULTS: Median overall and recurrence
      free survivals were 32 and 16 months, while 5-year overall and recurrence-free
      survival rates were estimated to be 38.2% and 35.9%, respectively. Ninety-six
      (52%) patients developed recurrence: 56 (30%) extrapancreatic, 27 (15%)
      locoregional, and 13 (7%) combined locoregional and extrapancreatic. Thirty-seven
      (19.9%) patients had early recurrence (within 6 months of operation). In the
      multivariable analysis, tumor size >3 cm and no adjuvant chemotherapy were
      associated with early recurrence (P = .017 and P = .015, respectively). The Cox
      regression model showed that tumor size >3 cm and lymphovascular invasion were
      independent predictors of decreased recurrence-free and overall survival.
      CONCLUSION: Standard laparoscopic distal pancreatectomy is associated with
      satisfactory long-term oncologic outcomes in patients with pancreatic ductal
      adenocarcinoma. Several risk factors, such as tumor size >3 cm, no adjuvant
      chemotherapy, and lymphovascular invasion, are linked to poor prognosis after
      standard laparoscopic distal pancreatectomy.

PMID- 28756945
TI  - SIRT1 Functions as a Negative Regulator of Eukaryotic Poly(A)RNA Transport.
AB  - Most eukaryotic mRNAs are polyadenylated in the nucleus, and the poly(A)-tail is
      required for efficient mRNA export and translation. However, mechanisms governing
      mRNA transport remain unclear. Here, we report that the nicotinamide adenine
      dinucleotide (NAD)-dependent deacetylase SIRT1 acts as an energy sensor and
      negatively regulates poly(A)RNA transport via deacetylating a poly(A)-binding
      protein, PABP1. Upon energy starvation, SIRT1 interacts with and deacetylates
      PABP1 and deactivates its poly(A)RNA binding, leading to nuclear accumulation of
      PABP1 and poly(A)RNA and thus facilitating eukaryotic cells to attenuate protein
      synthesis and energy consumption to adapt to energy stress. Moreover, AMPK
      directed SIRT1 phosphorylation is required for energy starvation-induced PABP1
      SIRT1 association, PABP1 deacetylation, and poly(A)RNA nuclear retention. In
      addition, the SIRT1-PABP1 association is not specific to energy starvation but
      represents a common stress response. These observations provide insights into
      dynamic modulation of eukaryotic mRNA transport and translation, suggesting that
      the poly(A)-tail also provides a basis for eukaryotes to effectively shut down
      mature mRNA transport and thereby tailor protein synthesis to maintain energy
      homeostasis under stress conditions.

PMID- 28756946
TI  - Fragile X Mental Retardation Protein Requirements in Activity-Dependent Critical
      Period Neural Circuit Refinement.
AB  - Activity-dependent synaptic remodeling occurs during early-use critical periods,
      when naive juveniles experience sensory input. Fragile X mental retardation
      protein (FMRP) sculpts synaptic refinement in an activity sensor mechanism based
      on sensory cues, with FMRP loss causing the most common heritable autism spectrum
      disorder (ASD), fragile X syndrome (FXS). In the well-mapped Drosophila olfactory
      circuitry, projection neurons (PNs) relay peripheral sensory information to the
      central brain mushroom body (MB) learning/memory center. FMRP-null PNs reduce
      synaptic branching and enlarge boutons, with ultrastructural and synaptic
      reconstitution MB connectivity defects. Critical period activity modulation via
      odorant stimuli, optogenetics, and transgenic tetanus toxin neurotransmission
      block show that elevated PN activity phenocopies FMRP-null defects, whereas PN
      silencing causes opposing changes. FMRP-null PNs lose activity-dependent synaptic
      modulation, with impairments restricted to the critical period. We conclude that
      FMRP is absolutely required for experience-dependent changes in synaptic
      connectivity during the developmental critical period of neural circuit
      optimization for sensory input.

PMID- 28756947
TI  - Two-Element Transcriptional Regulation in the Canonical Wnt Pathway.
AB  - The canonical Wnt pathway regulates numerous fundamental processes throughout
      development and adult physiology and is often disrupted in diseases [1-4]. Signal
      in the pathway is transduced by beta-catenin, which in complex with Tcf/Lef
      regulates transcription. Despite the many processes that the Wnt pathway governs,
      beta-catenin acts primarily on a single cis element in the DNA, the Wnt
      responsive element (WRE), at times potentiated by a nearby Helper site. In this
      study, working with Xenopus, mouse, and human systems, we identified a cis
      element, distinct from WRE, upon which beta-catenin and Tcf act. The element is
      11 bp long, hundreds of bases apart from the WRE, and exhibits a suppressive
      effect. In Xenopus patterning, loss of the 11-bp negative regulatory elements (11
      bp NREs) broadened dorsal expression of siamois. In mouse embryonic stem cells,
      genomic deletion of the 11-bp NREs in the promoter elevated Brachyury expression.
      This reveals a previously unappreciated mechanism within the Wnt pathway, where
      gene response is not only driven by WREs but also tuned by 11-bp NREs. Using
      electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation
      (ChIP), we found evidence for the NREs binding to beta-catenin and Tcf-suggesting
      a dual action by beta-catenin as a signal and a feedforward sensor. Analyzing
      beta-catenin ChIP sequencing in human cells, we found the 11-bp NREs co
      localizing with the WRE in 45%-71% of the peaks, suggesting a widespread role for
      the mechanism. This study presents an example of a more complex cis regulation by
      a signaling pathway, where a signal is processed through two distinct cis
      elements in a gene circuitry.

PMID- 28756948
TI  - The Sleeping Infant Brain Anticipates Development.
AB  - From the age of 3 months, infants learn relations between objects and co
      occurring words [1]. These very first representations of object-word pairings in
      infant memory are considered as non-symbolic proto-words comprising specific
      visual-auditory associations that can already be formed in the first months of
      life [2-5]. Genuine words that refer to semantic long-term memory have not been
      evidenced prior to 9 months of age [6-9]. Sleep is known to facilitate the
      reorganization of memories [9-14], but its impact on the perceptual-to-semantic
      trend in early development is unknown. Here we explored the formation of word
      meanings in 6- to 8-month-old infants and its reorganization during the course of
      sleep. Infants were exposed to new words as labels for new object categories. In
      the memory test about an hour later, generalization to novel category exemplars
      was tested. In infants who took a short nap during the retention period, a brain
      response of 3-month-olds [1] was observed, indicating generalizations based on
      early developing perceptual-associative memory. In those infants who napped
      longer, a semantic priming effect [15, 16] usually found later in development [17
      19] revealed the formation of genuine words. The perceptual-to-semantic shift in
      memory was related to the duration of sleep stage 2 and to locally increased
      sleep spindle activity. The finding that, after the massed presentation of
      several labeled category exemplars, sleep enabled even 6-month-olds to create
      semantic long-term memory clearly challenges the notion that immature brain
      structures are responsible for the typically slower lexical development.

PMID- 28756950
TI  - Grid Cells Encode Local Positional Information.
AB  - The brain has an extraordinary ability to create an internal spatial map of the
      external world [1]. This map-like representation of environmental surroundings is
      encoded through specific types of neurons, located within the hippocampus and
      entorhinal cortex, which exhibit spatially tuned firing patterns [2, 3]. In
      addition to encoding space, these neurons are believed to be related to
      contextual information and memory [4-7]. One class of such cells is the grid
      cells, which are located within the entorhinal cortex, presubiculum, and
      parasubiculum [3, 8]. Grid cell firing forms a hexagonal array of firing fields,
      a pattern that is largely thought to reflect the operation of intrinsic self
      motion-related computations [9-12]. If this is the case, then fields should be
      relatively uniform in size, number of spikes, and peak firing rate. However, it
      has been suggested that this is not in fact the case [3, 13]. The possibility
      exists that local spatial information also influences grid cells, which-if true
      would greatly change the way in which grid cells are thought to contribute to
      place coding. Accordingly, we asked how discriminable the individual fields of a
      given grid cell are by looking at the distribution of field firing rates and
      reproducibility of this distribution across trials. Grid fields were less uniform
      in intensity than expected, and the pattern of strong and weak fields was
      spatially stable and recurred across trials. The distribution remained unchanged
      even after arena rescaling, but not after remapping. This suggests that
      additional local information is being overlaid onto the global hexagonal pattern
      of grid cells.

PMID- 28756949
TI  - Expanded Satellite Repeats Amplify a Discrete CENP-A Nucleosome Assembly Site on
      Chromosomes that Drive in Female Meiosis.
AB  - Female meiosis provides an opportunity for selfish genetic elements to violate
      Mendel's law of segregation by increasing the chance of segregating to the egg
      [1]. Centromeres and other repetitive sequences can drive in meiosis by cheating
      the segregation process [2], but the underlying mechanisms are unknown. Here, we
      show that centromeres with more satellite repeats house more nucleosomes that
      confer centromere identity, containing the histone H3 variant CENP-A, and bias
      their segregation to the egg relative to centromeres with fewer repeats. CENP-A
      nucleosomes predominantly occupy a single site within the repeating unit that
      becomes limiting for centromere assembly on smaller centromeres. We propose that
      amplified repetitive sequences act as selfish elements by promoting expansion of
      CENP-A chromatin and increased transmission through the female germline.

PMID- 28756952
TI  - Wild Birds Use an Ordering Rule to Decode Novel Call Sequences.
AB  - The generative power of human language depends on grammatical rules, such as word
      ordering, that allow us to produce and comprehend even novel combinations of
      words [1-3]. Several species of birds and mammals produce sequences of calls [4
      6], and, like words in human sentences, their order may influence receiver
      responses [7]. However, it is unknown whether animals use call ordering to
      extract meaning from truly novel sequences. Here, we use a novel experimental
      approach to test this in a wild bird species, the Japanese tit (Parus minor).
      Japanese tits are attracted to mobbing a predator when they hear conspecific
      alert and recruitment calls ordered as alert-recruitment sequences [7]. They also
      approach in response to recruitment calls of heterospecific individuals in mixed
      species flocks [8, 9]. Using experimental playbacks, we assess their responses to
      artificial sequences in which their own alert calls are combined into different
      orderings with heterospecific recruitment calls. We find that Japanese tits
      respond similarly to mixed-species alert-recruitment call sequences and to their
      own alert-recruitment sequences. Importantly, however, tits rarely respond to
      mixed-species sequences in which the call order is reversed. Thus, Japanese tits
      extract a compound meaning from novel call sequences using an ordering rule.
      These results demonstrate a new parallel between animal communication systems and
      human language, opening new avenues for exploring the evolution of ordering rules
      and compositionality in animal vocal sequences.

PMID- 28756951
TI  - Piercing of Consciousness as a Threshold-Crossing Operation.
AB  - Many decisions arise through an accumulation of evidence to a terminating
      threshold. The process, termed bounded evidence accumulation (or drift
      diffusion), provides a unified account of decision speed and accuracy, and it is
      supported by neurophysiology in human and animal models. In many situations, a
      decision maker may not communicate a decision immediately and yet feel that at
      some point she had made up her mind. We hypothesized that this occurs when an
      accumulation of evidence reaches a termination threshold, registered,
      subjectively, as an "aha" moment. We asked human participants to make perceptual
      decisions about the net direction of dynamic random dot motion. The difficulty
      and viewing duration were controlled by the experimenter. After indicating their
      choice, participants adjusted the setting of a clock to the moment they felt they
      had reached a decision. The subjective decision times (tSDs) were faster on
      trials with stronger (easier) motion, and they were well fit by a bounded drift
      diffusion model. The fits to the tSDs alone furnished parameters that fully
      predicted the choices (accuracy) of four of the five participants. The quality of
      the prediction provides compelling evidence that these subjective reports
      correspond to the terminating process of a decision rather than a post hoc
      inference or arbitrary report. Thus, conscious awareness of having reached a
      decision appears to arise when the brain's representation of accumulated evidence
      reaches a threshold or bound. We propose that such a mechanism might play a more
      widespread role in the "piercing of consciousness" by non-conscious thought
      processes.

PMID- 28756953
TI  - Gut Microbiota Modifies Olfactory-Guided Microbial Preferences and Foraging
      Decisions in Drosophila.
AB  - The gut microbiota affects a wide spectrum of host physiological traits,
      including development [1-5], germline [6], immunity [7-9], nutrition [4, 10, 11],
      and longevity [12, 13]. Association with microbes also influences fitness-related
      behaviors such as mating [14] and social interactions [15, 16]. Although the gut
      microbiota is evidently important for host wellbeing, how hosts become associated
      with particular assemblages of microbes from the environment remains unclear.
      Here, we present evidence that the gut microbiota can modify microbial and
      nutritional preferences of Drosophila melanogaster. By experimentally
      manipulating the gut microbiota of flies subjected to behavioral and chemosensory
      assays, we found that fly-microbe attractions are shaped by the identity of the
      host microbiota. Conventional flies exhibit preference for their associated
      Lactobacillus, a behavior also present in axenic flies as adults and marginally
      as larvae. By contrast, fly preference for Acetobacter is primed by early-life
      exposure and can override the innate preference. These microbial preferences are
      largely olfactory guided and have profound impact on host foraging, as flies
      continuously trade off between acquiring beneficial microbes and balancing
      nutrients from food. Our study shows a role of animal microbiota in shaping host
      fitness-related behavior through their chemosensory responses, opening a research
      theme on the interrelationships between the microbiota, host sensory perception,
      and behavior.

PMID- 28756954
TI  - Illusory Jitter Perceived at the Frequency of Alpha Oscillations.
AB  - Neural oscillations, such as alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-100
      Hz), are widespread across cortical areas, and their possible functional roles
      include feature binding [1], neuronal communication [2, 3], and memory [1, 4].
      The most prominent signal among these neural oscillations is the alpha
      oscillation. Although accumulating evidence suggests that alpha oscillations
      correlate with various aspects of visual processing [5-18], the number of studies
      proving their causal contribution in visual perception is limited [11, 16-18].
      Here we report that illusory visual vibrations are consciously experienced at the
      frequency of intrinsic alpha oscillations. We employed an illusory jitter
      perception termed the motion-induced spatial conflict [19] that originates from
      the cyclic interaction between motion and shape processing. Comparison between
      the perceived frequency of illusory jitter and the peak alpha frequency (PAF)
      measured using magnetoencephalography (MEG) revealed that the inter- and intra
      participant variations of the PAF are mirrored by an illusory jitter perception.
      More crucially, psychophysical and MEG measurements during amplitude-modulated
      current stimulation [20] showed that the PAF can be artificially manipulated,
      which results in a corresponding change in the perceived jitter frequency. These
      results suggest the causal contribution of neural oscillations at the alpha
      frequency in creating temporal characteristics of visual perception. Our results
      suggest that cortical areas, dorsal and ventral visual areas in this case, are
      interacting at the frequency of alpha oscillations [2, 3, 21-27].

PMID- 28756956
TI  - Local Failure After Episcleral Brachytherapy for Posterior Uveal Melanoma:
      Patterns, Risk Factors, and Management.

PMID- 28756955
TI  - Whole-Brain Calcium Imaging Reveals an Intrinsic Functional Network in
      Drosophila.
AB  - A long-standing goal of neuroscience has been to understand how computations are
      implemented across large-scale brain networks. By correlating spontaneous
      activity during "resting states" [1], studies of intrinsic brain networks in
      humans have demonstrated a correspondence with task-related activation patterns
      [2], relationships to behavior [3], and alterations in processes such as aging
      [4] and brain disorders [5], highlighting the importance of resting-state
      measurements for understanding brain function. Here, we develop methods to
      measure intrinsic functional connectivity in Drosophila, a powerful model for the
      study of neural computation. Recent studies using calcium imaging have measured
      neural activity at high spatial and temporal resolution in zebrafish, Drosophila
      larvae, and worms [6-10]. For example, calcium imaging in the zebrafish brain
      recently revealed correlations between the midbrain and hindbrain, demonstrating
      the utility of measuring intrinsic functional connections in model organisms [8].
      An important component of human connectivity research is the use of brain atlases
      to compare findings across individuals and studies [11]. An anatomical atlas of
      the central adult fly brain was recently described [12]; however, combining an
      atlas with whole-brain calcium imaging has yet to be performed in vivo in adult
      Drosophila. Here, we measure intrinsic functional connectivity in Drosophila by
      acquiring calcium signals from the central brain. We develop an alignment
      procedure to assign functional data to atlas regions and correlate activity
      between regions to generate brain networks. This work reveals a large-scale
      architecture for neural communication and provides a framework for using
      Drosophila to study functional brain networks.

PMID- 28756957
TI  - Comparison of the Diameters of the Major Epicardial Coronary Arteries by
      Angiogram in Asian-Indians Versus European Americans <40 Years of Age Undergoing
      Percutaneous Coronary Artery Intervention.
AB  - Coronary artery disease (CAD) rates are higher in Asian-Indians than in
      Caucasians. CAD occurs at an earlier age in this group, with about a quarter of
      all myocardial infarctions occurring under the age of 40. Previous reports have
      suggested smaller coronary artery size in Asian-Indians as a major cause for
      increased CAD in this population. This study sought to evaluate the size of
      normal "atheroma-free" segments of the epicardial coronary arteries in Asian
      Indians and Caucasians aged <=40 years undergoing coronary artery intervention in
      other diseased segments. A total of 69 consecutive patients (41 whites, 28 Asian
      Indians) aged <=40 years were evaluated. Angiograms were analyzed using standard
      quality control analysis software with digital acquisition. The arteries measured
      were the left main, left anterior descending, left circumflex, and the right
      coronary artery. Conventional risk factors, including hypertension, smoking, and
      diabetes, that could influence coronary size were also assessed. The coronary
      arteries of Asian-Indian patients showed significantly smaller values in the mean
      diameters of the left main (2.96 mm vs 4.04 mm, p = 0.0004), left anterior
      descending (2.48 mm vs 3.24 mm, p = 0.0005), left circumflex (2.52 mm vs 3.06 mm,
      p = 0.00002), and right coronary artery (2.71 mm vs 3.65 mm, p = 0.0008) as
      compared with Caucasians. Even after correction for body surface area, a
      statistically significant difference remained in coronary artery diameters. In
      conclusion, statistically significant difference in the mean diameter size even
      after correction for body surface area in Asian-Indians has implications for
      predisposition to atherosclerosis, and more challenging performance of procedures
      such as coronary artery bypass grafting, stent implantation, or atherectomy.

PMID- 28756958
TI  - New Insight into the Dissolution of Epoxy Resin-based Sealers.
AB  - INTRODUCTION: The purpose of this study was to evaluate the use of solvents that
      are not traditionally used in dentistry for the dissolution of an epoxy resin
      based sealer and the effect of ultrasonic agitation (UA). METHODS: The
      dissolution of the AH Plus sealer (Dentsply DeTrey, Konstanz, Germany) and the
      effect of UA in various solvents (eucalyptol, xylene, chloroform, EndoSolv R
      [Septodont, Cedex, France], EndoSolv E [Septodont], methyl ethyl ketone [MEK],
      and ethyl acetate) were quantified. The dissolving capacity was assessed by
      weight loss, Vicker microhardness, scanning electron microscopy (SEM), and X-ray
      diffraction (XRD). The results were compared with factorial analysis of variance
      using IBM SPSS Statistics 23.0 software (IBM, Armonk, NY), considering a 0.05
      significance level. A preliminary ex vivo study was performed in extracted teeth,
      with MEK activated by UA as the final irrigation after mechanical removal of the
      filling material. SEM was used for assessing the cleanliness of the root canal
      walls. RESULTS: The new solvent proposals, ethyl acetate and MEK, exhibited high
      dissolution ability, almost reaching chloroform. UA increased dissolution. Vicker
      values corroborated the dissolution assays. SEM and XRD revealed that solvents
      affected mainly the organic component of the sealer. Ex vivo results confirmed
      the immersion model findings. CONCLUSIONS: MEK and ethyl acetate proved to be
      excellent alternatives to chloroform or xylene solvents. MEK presented a high
      sealer dissolving ability in a short period, especially with UA, without the
      potential hazards of chloroform, suggesting it is a good approach to AH Plus
      sealer's dissolution empowered by UA. These results should encourage further
      studies in order to confirm their clinical relevance.

PMID- 28756959
TI  - Association of Failed Root Canal Treatment with Dentist and Institutional
      Volumes: A Population-based Cohort Study in Taiwan.
AB  - INTRODUCTION: The volume-outcome relationships in failed root canal treatments
      (RCTs) are rarely studied. Thus, we aimed to examine the association of failed
      RCTs with dentist and institutional volumes. METHODS: Ambulatory dental claims
      (2005-2010) of 1 million beneficiaries randomly selected from the National Health
      Insurance Research Database of Taiwan were used. This study is a population-based
      cohort study using a marginal Cox proportional hazards regression model in which
      the outcome variables cluster around individual patients. A total of 458,557
      teeth that received first-ever RCT from 2005 to 2010 and were followed up until
      the end of 2010 were identified as the tooth cohort. These teeth were aggregated
      to 244,368 patients, 10,901 dentists, and 7122 institutions for analysis.
      RESULTS: Dentists in the second, third, and highest quartiles all showed a
      significantly lower hazard ratio of failed RCTs than those with the lowest case
      volume, and their adjusted hazard ratios (aHRs) were 0.93, 0.92, and 0.90,
      respectively. Medical institutions in the second, third, and highest quartiles
      also showed a significantly lower hazard ratio of failed RCTs than those with the
      lowest case volume, and their aHRs were 0.93, 0.89, and 0.81, respectively. Teeth
      with a history of periodontitis also exhibited a significantly higher aHR of
      failure events. The use of rubber dams significantly reduced the rates of failed
      RCTs. CONCLUSIONS: Dentists and institutions with high care volumes tended to
      show good RCT outcomes. Such an effect was prominent and robust among dental
      institutions.

PMID- 28756960
TI  - Influence of Apical Periodontitis on Stress Oxidative Parameters in Diabetic
      Rats.
AB  - INTRODUCTION: In this study, we investigated if apical periodontitis (AP)
      associated with diabetes influenced the levels of endogenous antioxidants, the
      total antioxidant capacity (TAC), and the oxidant parameter in the serum of
      Wistar rats. METHODS: Forty male rats were divided into 4 equal groups: normal
      rats (N), rats with AP (AP), diabetic rats (D), and diabetic rats with AP (D +
      AP). Diabetes was induced by alloxan (150 mg/kg). AP was induced by exposing the
      pulpal tissue to the oral environment. After 36 days, blood and maxillae were
      collected. Albumin, bilirubin, uric acid, TAC, and malondialdehyde (MDA) levels
      were measured, and histologic analysis of the maxillae was performed. P < .05 was
      set as the threshold for statistical significance. RESULTS: Uric acid levels were
      higher in the D + AP group when compared with that of the N, D, and AP groups (P
      < .05). The MDA concentration was higher in the D and D + AP groups when compared
      with the N and AP groups (P < .05). The level of albumin was lower in the D + AP
      group when compared with the N, AP, and D groups. Inflammatory infiltration was
      more intense in the periapical region in the D + AP group compared with that in
      the AP group (P < .05). CONCLUSIONS: Our findings indicate that diabetes may
      change the antioxidant status, increase the concentration of MDA and uric acid,
      and decrease albumin levels in the serum. In addition, AP can potentiate the
      effects of diabetes by reducing the levels of albumin and increasing the levels
      of uric acid.

PMID- 28756961
TI  - Efficacy of Photon-induced Photoacoustic Streaming in the Reduction of
      Enterococcus faecalis within the Root Canal: Different Settings and Different
      Sodium Hypochlorite Concentrations.
AB  - INTRODUCTION: The purpose of this study was to determine the effectiveness of
      laser-activated irrigation by photon-induced photoacoustic streaming (PIPS) in
      the reduction of Enterococcus faecalis in root canal disinfection, varying laser
      energy output, and sodium hypochlorite (NaOCl) concentration. For effective
      removal of the smear layer, the sequence and resting time of the final irrigation
      steps were modified compared with the standard PIPS protocol. METHODS: Eighty-six
      extracted single-rooted teeth were mechanically prepared, sterilized, and
      inoculated with E. faecalis for 4 weeks. Teeth were divided into 9 groups and
      treated with an Er:YAG laser using a PIPS 600/9 tip at the following parameters:
      10 mJ or 20 mJ, 15 Hz, and a 50-microsecond pulse duration at 0.15 W or 0.3 W
      average power, respectively. Root canals were irrigated with different
      concentrations of NaOCl (ie, 1%, 3%, and 5% and activated using the adjusted PIPS
      protocol). The bacterial count was performed immediately after and 48 hours after
      decontamination and new incubation on an agar plate. RESULTS: A statistically
      significant difference in bacterial counts (P < .05) was detected in all groups
      before and directly after the treatment and in groups treated with 5% NaOCl 48
      hours after treatment. Scanning electron microscopic imaging showed an absence of
      bacteria and biofilm in the scanned areas after treatment with 5% NaOCl.
      CONCLUSIONS: Laser-activated irrigation using 5% NaOCl and a modified PIPS
      protocol resulted in effective eradication of the bacterial biofilm and removal
      of the smear layer.

PMID- 28756962
TI  - Evaluation of Different Techniques for Filling Simulated C-shaped Canals of 3
      dimensional Printed Resin Teeth.
AB  - INTRODUCTION: The purpose of this study was to compare the ability of different
      root canal filling methods on the C1 root canal anatomy using 3-dimensional (3D)
      printer technology. METHODS: Mandibular molars were scanned with cone-beam
      computed tomographic (CBCT) imaging. A mandibular molar tooth with a C1 root
      canal configuration was selected according to images obtained from CBCT
      technology. The root canals were shaped with ProTaper Universal rotary
      instruments (Dentsply Maillefer, Ballaigues, Switzerland) and hand files. After
      the root canal shaping procedure, the tooth was scanned with micro-computed
      tomographic imaging, and 80 replicas of the tooth were produced with a 3D
      printer. Replicas were assigned into 4 groups (n = 20) and were filled using one
      of the following techniques: a core carrier system (GuttaCore [GC]; Dentsply
      Tulsa Dental Specialties, Tulsa, OK), a continuous wave obturation system
      (Elements Free [CW]; Kerr/SybronEndo, Orange, CA), a cold lateral compaction
      technique (CLC), or the injectable cold filling method (GuttaFlow Bioseal [GFB];
      Coltene/Whaledent AG, Altstatten, Switzerland). All specimens were sectioned
      horizontally at 2, 4, 6, 8, and 10 mm from the apices of the specimens. The
      sections were examined at 32* magnification under a stereomicroscope, and the
      percentage areas of gutta-percha, sealer, and voids were measured. Statistical
      analysis of data was performed using multivariate analysis of variance and Tukey
      honestly significant difference tests (P < .05). RESULTS: The CW group had the
      highest mean percentages for void and the least mean percentages for gutta-percha
      at 2-mm sections (P < .05). A pairwise comparison between the groups showed
      significantly less void in the CLC and GFB groups and more void in the CW and GC
      groups at 2 mm (P < .05). In the total area, the CLC and GFB groups showed a
      significantly lower percentage of gutta-percha and more sealer compared with the
      other groups (P < .05), and there was no significant difference between the CLC
      and GFB groups (P > .05). CONCLUSIONS: At the apical part of the canal, the cold
      lateral compaction and cold injectable filling techniques were more successful
      compared with the warm gutta-percha filling techniques in C1 root canal
      configuration.

PMID- 28756963
TI  - Micro-computed Tomographic Evaluation of Dentinal Microcrack Formation after
      Using New Heat-treated Nickel-titanium Systems.
AB  - INTRODUCTION: The aim of the present study was to evaluate the frequency of
      dentinal microcracks observed after root canal preparation with HyFlex CM
      (Coltene/Whaledent, Altstatten, Switzerland), HyFlex EDM (Coltene/Whaledent),
      Vortex Blue (Dentsply Tulsa Dental Specialties, Tulsa, OK), and TRUShape
      (Dentsply Tulsa Dental Specialties) systems using micro-computed tomographic
      (micro-CT) analysis. METHODS: Forty human mandibular incisors with 1 and straight
      root canals were randomly assigned to 4 experimental groups (n = 10) and 1
      control group for root canal preparation: group 1, HyFlex CM; group 2, HyFlex
      EDM; group 3, Vortex Blue; and group 4, TRUShape. The specimens were scanned
      using high-resolution micro-CT imaging before and after root canal preparation.
      Afterward, preoperative and postoperative cross-sectional images of the teeth
      were screened to identify the presence of dentinal defects. The number of
      microcracks was determined as a percentage for each group. RESULTS: Before and
      after canal preparation, 36,152 cross-sectional images were examined. Four
      thousand four hundred fifty-two (12.31%) dentinal defects were observed. No new
      microcracks were observed after root canal instrumentation with the tested
      systems. CONCLUSIONS: Root canal preparation with the HyFlex CM, HyFlex EDM,
      Vortex Blue, and TRUShape systems did not induce the formation of new dentinal
      microcracks on straight root canals of mandibular incisors.

PMID- 28756965
TI  - Drug-related problems in geriatric rehabilitation patients after discharge - A
      prevalence analysis and clinical case scenario-based pilot study.
AB  - BACKGROUND: Geriatric patients bear a high risk for having drug-related problems
      (DRPs). Transitions of care are especially susceptible to these DRPs. OBJECTIVE:
      To highlight the prevalence of DRPs in geriatric patients' post-discharge
      medication lists and to assess physicians' ability to identify DRPs by using
      clinical case scenarios. METHODS: A sequential prospective mixed-method study was
      performed. In a DRP prevalence analysis, an expert panel of clinical pharmacists
      analyzed DRPs in post-discharge medication lists of long-term hospitalized
      patients from a German inpatient geriatric rehabilitation center. Based on these
      results, the expert panel created two clinical case scenarios with applicable
      medication history. The cases were reflective of the most commonly identified
      DRPs. They were provided to hospital physicians and general practitioners (GPs)
      for assessment. Physicians were asked whether they approve the prescriptions in
      the clinical case scenarios. If a physician had not identified a prescription
      containing a defined DRP, the clinical pharmacist then provided drug information
      about it. With this, physicians' ability to identify DRPs and their response to a
      theoretical intervention was assessed. RESULTS: DRP prevalence analysis: A total
      of 639 prescriptions were analyzed from 63 enrolled patients of whom 52 (83%)
      were affected by at least one DRP. Twenty-eight hospital physicians and 26 GPs
      have been assessed. They identified 172 (46%) from 378 possible DRPs (seven DRPs
      multiplied by 54 physicians). For unidentified DRPs, physicians received tailored
      drug information and the number of identified DRPs rose to 298 (79%).
      CONCLUSIONS: A clear majority of patients were affected by DRPs. However, the
      results from the following pilot study confirm that many DRPs at care transitions
      can be reduced by providing applicable medication history and drug information.
      This intervention can be done by clinical pharmacists as part of the
      multidisciplinary care team in routine care. SYNOPSIS: Geriatric patients bear a
      high risk for having drug-related problems (DRPs). Strategies to protect them are
      needed, especially during transitions of care due to information and knowledge
      gaps. Therefore a sequential prospective mixed method study was performed.
      Initial post-discharge medication lists of geriatric patients were analyzed for
      DRPs with 83% of patients being affected. Afterwards, physicians' ability to
      identify DRPs was assessed based on clinical case scenarios. These clinical case
      scenarios included an applicable medication history and tailored drug information
      was provided. Under these conditions, physicians identified many of the defined
      DRPs.

PMID- 28756966
TI  - Bone invasion by oral squamous cell carcinoma: Molecular alterations leading to
      osteoclastogenesis - a review of literature.
AB  - Oral squamous cell carcinoma (OSCC) is a growing problem globally. OSCC often
      arises in close anatomical relation to the jaws and may invade the bone. Bone
      invasion by OSCC has major implications on tumor staging, choice of treatment,
      outcome, and quality of life. The difference in cortical or medullary bone
      invasion has implications for these factors. Treatment protocols used for
      cortical and medullary invasion differ worldwide. By researching possible
      pathways a more molecular-based clinical staging and tailor-made therapy can be
      useful for patients with bone invasion by OSCC. An important molecular step in
      bone invasion seems to be the activation of osteoclasts. Several direct and
      indirect pathways can activate osteoclasts. Microbial infections, hypoxia, and
      the immune system could be of interest.

PMID- 28756964
TI  - Key features of invasive pneumococcal isolates recovered in Lima, Peru determined
      through whole genome sequencing.
AB  - Before PCV7 introduction, invasive pneumococcal disease (IPD) was responsible for
      approximately 12,000-18,000 deaths annually among children <5years in Latin
      America. In Peru, PCV7 was introduced in 2009. We used whole genome sequencing to
      deduce key features of invasive strains collected in Lima, Peru from 2006 to
      2011. We sequenced 212 IPD isolates from 16 hospitals in Lima pre (2006-2009;
      n=133) and post (2010-2011; n=79) PCV7 introduction; 130 (61.3%) isolates were
      from children<=5years old. CDC's Streptococcus lab bioinformatics pipeline
      revealed serotypes, sequence types (STs), pilus genes, PBP types and other
      resistance determinants. During the pre-PCV7 period, serotype 14 was the most
      common serotype (24.8%), followed by 6B (20.3%), 19F (10.5%), and 23F (6.8%).
      Post-PCV7, the proportion of PCV7 serotype 6B decreased significantly (to 6.3%),
      while 19F (16.3%), 14 (15.0%), 23F (7.5%), and 19A (7.5%) were the most common
      serotypes; only serotypes 3 and 10A increased significantly. Overall, 82% (n=173)
      of all isolates carried at least one resistance determinant, including 72 (34%)
      isolates that carried resistance determinants against 3 or more antimicrobial
      classes; of these 72 isolates, 56 (78%) belonged to a PCV7 serotype. Eighty-two
      STs were identified, with 53 of them organized in 14 clonal complexes. ST
      frequencies were distributed differently pre and post-PCV7 introduction, with
      only 18 of the 57 STs identified in years 2006-2009 isolates also observed in
      years 2010-2011 isolates. The apparent expansion of a 19F/ST1421 lineage with
      predicted beta-lactam resistance (PBP type 13:16:20) and carrying resistance
      determinants against four additional antimicrobial classes was observed.

PMID- 28756967
TI  - The self-defining axis of symmetry: A new method to determine optimal symmetry
      and its application and limitation in craniofacial surgery.
AB  - PURPOSE: Analysis of symmetry represents an essential aspect of plastic
      reconstructive surgery. For cases in which reference points are either not fixed
      or are changed due to corrective intervention the determination of a symmetry
      axis is sometimes almost impossible and a pre-defined symmetry axis would not
      always be helpful. To assess cranial shape of surgical patients with
      craniosynostosis, a new algebraic approach was chosen in which deviation from the
      optimal symmetry axis could be quantified. MATERIALS AND METHODS: Optimal
      symmetry was defined based on a single central point in the fronto-orbital
      advancement (FOA) hyperplane and a corresponding landmark pair. The forehead
      symmetry evaluation was based on 3D-scans series of 13 children, on whom
      cranioplasty with FOA was performed and 15 healthy children who served as control
      group. RESULTS: Children with plagiocephaly showed considerable improvement in
      symmetry postoperatively, with stable values over one year, while those with
      trigonocephaly and brachycephaly showed constant good symmetry in the forehead
      both pre- and postoperatively. CONCLUSIONS: With the help of an optimally
      calculated symmetry axis this new analysis method offers a solution, which is
      independent of preset dimensions. Patients can be evaluated according to their
      individual needs regarding symmetry and also be compared with one another.

PMID- 28756968
TI  - Fundamentals of Laparoscopic Surgery: Not Only for Senior Residents.
AB  - OBJECTIVE: Fundamentals of laparoscopic surgery (FLS) was developed by the
      Society of American Gastrointestinal and Endoscopic Surgeons to teach the
      physiology, fundamental knowledge, and technical skills required for basic
      laparoscopic surgery. We hypothesize that residents are doing more laparoscopic
      surgery earlier in residency, and therefore would benefit from an earlier
      assessment of basic laparoscopic skills. Here, we examine FLS test results and
      ACGME case logs to determine whether it is practical to administer FLS earlier in
      residency. DESIGN: FLS test results were reviewed for the 42 residents completing
      FLS between July 2011 and July 2016. ACGME case logs for current and former
      residents were reviewed for laparoscopic cases logged by each postgraduate year.
      Basic and complex laparoscopic cases were determined by ACGME General Surgery
      Defined Category and Minimums Report. Descriptive statistics were used for
      analysis. SETTING: Academic general surgery residency, Washington University in
      St. Louis School of Medicine. PARTICIPANTS: Current and former general surgery
      residents. RESULTS: A total of 42 residents took and passed FLS between July 2011
      and July 2016. All residents successfully passed the FLS knowledge and skills
      examinations on the first attempt regardless of their postgraduate year (PGY 3n =
      13, PGY 4n = 15, and PGY 5n = 14). Total laparoscopic case volume has increased
      over time. Residents who graduated in 2012 or 2013 completed 229 laparoscopic
      cases compared to 267 laparoscopic cases for those who graduated from 2014 to
      2016 (p = 0.02). Additionally, current residents completed more laparoscopic
      cases in the first 2 years of residency than residents who graduated from 2012 to
      2016 (median current = 38; former = 22; p < 0.001). Examining laparoscopic case
      numbers for current residents by PGY demonstrated that the number of total and
      complex laparoscopic cases increased in each of the first 3 years of residency
      with the largest increase occurring between the PGY 2 and PGY 3 years. In the PGY
      4 and PGY 5 years, most laparoscopic cases were complex. CONCLUSION: Increased
      use of laparoscopic surgery has led to a corresponding increase in laparoscopic
      case volume among general surgery residents. We would advocate for FLS testing to
      serve as an early assessment of laparoscopic knowledge and skill and should be
      performed before a significant increase in complex laparoscopic surgery during
      training.

PMID- 28756969
TI  - The Right Way to Teach Left-Handed Residents: Strategies for Training by Right
      Handers.
AB  - PURPOSE: Left-handed (LH) residents remain underrepresented among surgical
      trainees, and there are few available data on how best to train them. The
      challenge is amplified when pairing a LH resident with a right-handed (RH)
      mentor. This report provides recommendations on how to improve the training of LH
      surgeons in a safe and effective manner. METHODS: A comprehensive literature
      review was performed using different databases and search engines to identify all
      articles relevant to the training of LH residents. RESULTS: A total of 40
      articles highlighted the challenges for LH surgical residents and RH mentors. Our
      recommendations are based on the following 4 themes: identifying inherent
      differences in left vs. RH residents, providing guidance to RH mentors training
      LH residents, adapting the RH environment to the LH surgeon, and maximizing
      safety during training. CONCLUSION: An organized approach needs to be taken in
      training the LH resident. Changes should be instituted at program-wide and
      national levels to ensure that the training experience of the sinistral surgical
      resident is optimized.

PMID- 28756970
TI  - Phase-separated surfactant monolayers: Exploiting immiscibility of fluorocarbons
      and hydrocarbons to pattern interfaces.
AB  - The mutual immiscibility of hydrogenated and fluorinated surfactants at
      interfaces frequently leads to phase-separation, which provides a useful and
      flexible method for patterning air-water and solid-air interfaces. In this
      article, we review recent advances in the use of hydrogenated-fluorinated
      surfactant mixtures to achieve interfacial patterning. For even relatively simple
      systems comprised of binary mixed monolayers of hydrogenated and perfluorinated
      fatty acids, a diverse range of film morphologies can be generated at the air
      water interface and successfully transferred onto solid substrates. Systematic
      investigations reported over the past several years have allowed for correlation
      between the chemical structure of the film constituents with the gross film
      morphology and underlying crystalline structure of the films. Early thermodynamic
      models based on the interplay between dipole-dipole repulsion forces between
      charged headgroups balanced by line tension between phases that were formulated
      to describe phase-behavior in simple phospholipid monolayer systems have proven
      highly useful to describe morphologies for the immiscible surfactant blends.
      Beyond simple binary fatty acid mixtures, highly-structured films have also been
      reported in mixed phospholipid systems, which have found important application in
      controlling the physical, compositional and performance properties of lung
      surfactant mixtures, as well as in semifluorinated alkane monolayers which form
      unique, hemimicellar structures at both liquid and solid interfaces. We also
      describe advances in using these approaches to pattern photopolymerizable,
      luminescent surfactants, which have found extensive use in colorimetric and
      fluorometric sensing devices. The long-term outlook for this field, with an
      emphasis on potential applications and future research directions are discussed.

PMID- 28756971
TI  - Associations of tissue transglutaminase antibody seropositivity with coronary
      heart disease: Findings from a prospective cohort study.
AB  - BACKGROUND AND AIMS: Clinical experience and observational studies suggest that
      individuals with coeliac disease are at increased risk of coronary heart disease
      (CHD), but the precise mechanism for this is unclear. Laboratory studies suggest
      that it may relate to tissue transglutaminase antibodies (tTGAs). Our aim was to
      examine whether seropositivity for tTGA and endomysial antibodies (EMAs) are
      associated with incident CHD in humans. METHODS AND RESULTS: We used data from
      Mini-Finland Health Survey, a prospective cohort study of Finnish men and women
      aged 35-80 at study baseline 1978-80. TTGA and EMA seropositivities were
      ascertained from baseline blood samples and incident CHD events were identified
      from national hospitalisation and death registers. Cox regression was used to
      examine the associations between antibody seropositivity and incident CHD. Of
      6887 men and women, 562 were seropositive for tTGAs and 72 for EMAs. During a
      median follow-up of 26 years, 2367 individuals experienced a CHD event. We found
      no clear evidence for an association between tTGA positivity (hazard ratio, HR:
      1.04, 95% confidence interval, CI: 0.83, 1.30) or EMA positivity (HR: 1.16, 95%
      CI: 0.77, 1.74) and incident CHD, once pre-existing CVD and known CHD risk
      factors had been adjusted for. CONCLUSION: We found no clear evidence for an
      association of tTGA or EMA seropositivity with incident CHD outcomes, suggesting
      that tTG autoimmunity is unlikely to be the biological link between coeliac
      disease and CHD.

PMID- 28756973
TI  - Extracorporeal membrane oxygenation support may be a lifesaving modality in
      patients with burn and severe acute respiratory distress syndrome: Experience of
      Formosa Water Park dust explosion disaster in Taiwan.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been reported to
      improve outcomes in patients with refractory respiratory failure. These
      successful experiences have stimulated interest in using ECMO as a potential
      therapy for patients with acute pulmonary failure resulting from burn and
      inhalation lung injury. Current literature has supported the use of ECMO in
      critically-ill, pediatric burn patients. On the other hand, it is controversial
      to apply ECMO in adult burn patients, and the evidence is limited by the
      shortcomings of small sample size. We share our successful experience of ECMO
      treatment in the casualties of the Formosa Water Park Dust Explosion Disaster.
      METHODS: We investigated the data from the dust explosion event, which happened
      on June 27, 2015, in New Taipei, Taiwan. The medical records of five patients
      with severe acute respiratory distress syndrome receiving ECMO were evaluated.
      RESULTS: The mean study subject age was 21.8 years, with a mean total body
      surface area burned of 82.9%. The average time to ECMO setup was 48.6 days.
      Survivors and non-survivors averaged four days and 77.7 days, respectively. The
      overall mortality rate was 40%. Three survivors were discharged without any ECMO
      related complications or pulmonary sequelae after one year of follow up.
      CONCLUSIONS: ECMO may be a lifesaving modality for burn patients with severe lung
      injury who are nonresponsive to maximal medical management, especially for young
      patients with early ECMO intervention.

PMID- 28756972
TI  - Seasonality of sodium and potassium consumption in Switzerland. Data from three
      cross-sectional, population-based studies.
AB  - BACKGROUND AND AIM: Blood pressure displays a seasonal pattern. Whether this
      pattern is related to high sodium and/or low potassium intakes has not been
      investigated. We assessed if sodium and potassium consumption present a seasonal
      pattern. We also simulated the impact of seasonality of sodium consumption on
      systolic blood pressure levels. METHODS AND RESULTS: Data from three Swiss
      population-based studies (n = 2845). Sodium and potassium consumption were
      assessed by urinary excretion using 24 h urine collection. Seasonality was
      assessed using the cosinor model and was adjusted for study, gender, age, body
      mass index, antihypertensive drug treatment, urinary creatinine and atmospheric
      relative humidity. The effect of sodium variation on blood pressure levels was
      estimated using data from a recent meta-analysis. Both sodium and potassium
      excretions showed a seasonal pattern. For sodium, the nadir occurred between
      August and October, and the peak between February and April, with a multivariate
      adjusted seasonal variation (difference between peak and nadir) of 9.2 mmol. For
      potassium, the nadir occurred in October and the peak in April, with a
      multivariate-adjusted seasonal variation of 4.0 mmol. Excluding participants on
      antihypertensive drug treatment or stratifying the analysis by gender cancelled
      the seasonality of sodium consumption. The maximum impact of the seasonal
      variation in sodium consumption on systolic blood pressure ranged from 0.4 to 1.1
      mm Hg, depending on the model considered. CONCLUSION: Sodium and potassium
      consumptions present specific seasonal variations. These variations do not
      explain the seasonal variations in blood pressure levels.

PMID- 28756974
TI  - Incidence of and risk factors for pancreatic cancer in chronic pancreatitis: A
      cohort of 1656 patients.
AB  - BACKGROUND: Risk of pancreatic cancer may increase in chronic pancreatitis
      patients. AIMS: This study aimed to identify the incidence of and risk factors
      for pancreatic cancer in chronic pancreatitis patients. METHODS: Chronic
      pancreatitis patients admitted to our center from January 2000 to December 2013
      were enrolled. Cumulative rates of pancreatic cancer and survival rates were
      calculated. The standardized incidence ratio was calculated based on the
      pancreatic cancer incidence in general population of China. Risk factors for
      pancreatic cancer were identified. RESULTS: In a total of 1656 patients, the
      median follow-up duration was 8.0 years. Pancreatic cancer was detected in 21
      patients (1.3%). The expected number of cases of pancreatic cancer was 1.039,
      yielding a standardized incidence ratio of 20.22. The standardized incidence
      ratios for patients with a >60 pack-year smoking history were much higher
      (145.82). Two risk factors for pancreatic cancer were identified: age at the
      onset of chronic pancreatitis (hazard ratio, 1.05) and a >60 pack-year smoking
      history (hazard ratio, 11.83). CONCLUSION: The risk of pancreatic cancer is
      markedly increased in chronic pancreatitis patients compared with the general
      population, especially in patients with an older age at onset and a >60 pack-year
      smoking history. The high-risk populations were suggested to be followed up
      closely.

PMID- 28756975
TI  - Anatomy of the medial antebrachial cutaneous nerve and its significance in ulnar
      nerve surgery: An anatomical study.
AB  - BACKGROUND: During cubital tunnel surgery, the medial antebrachial cutaneous
      nerve (MACN) may be injured, causing painful scars, neuromas, hypaesthesia or
      hyperalgesia. As the literature on the anatomy of crossing branches in this area
      is contradictory, this study aimed to re-examine the anatomy of the MACN in this
      region. METHODS: Forty upper limbs were dissected. We looked specifically from 5
      cm proximal to 6 cm distal to the medial epicondyle (ME) and documented the
      number of crossing branches and the distances between the crossing points and the
      ME; we also measured the length of each limb. RESULTS: The most common location
      for crossing branches was 2 cm distal to the ME. Twenty-seven branches (~23%)
      were found proximal to or at the level of the ME, and 91 branches (~77%) were
      distal to it. The average distance between the proximal crossing points and the
      ME was 1.7 cm, the mean number of crossing branches was 0.7 and at least one
      crossing branch per limb was found in 16/40 cases. For the distal crossing
      points, the average distance to the ME was 2.9 cm, the mean number of crossing
      branches was 2.3 and at least one crossing branch per limb was found in all
      cases. There was no correlation between the limb lengths and the number of
      crossing branches. CONCLUSION: Because the incidence of posterior branches of the
      MACN crossing the course of the ulnar nerve is 100%, it is important to take the
      anatomy of the MACN into consideration when undertaking ulnar nerve surgery.

PMID- 28756976
TI  - Oncocytic papillary cystadenoma with prominent mucinous differentiation of
      parotid gland: A case report.
AB  - We describe the case of an oncocytic papillary cystadenoma with mucinous
      differentiation of the parotid gland in a 64-year-old male. Histologically, the
      tumor exhibited distinctive areas of intracystic papillary growth pattern with
      microcystic and macrocystic spaces containing mucinous secretions and small
      crystals. The cyst wall and papillary fronds were lined by oncocytic admixed with
      numerous mucocytes. Lymphoid tissue and invasive features were not identified.
      The tumor showed strong expression of CK7 and mammaglobin in oncocytes, and BRST
      2 and MUC4 in mucocytes. p63, ER, PR, SOX10, DOG-1, and S100 stains were
      negative. No rearrangement of the MAML2 gene region or ETV6-NTRK3 fusion
      transcript was detected. The diagnosis of oncocytic papillary tumor with
      prominent mucinous differentiation is particularly problematic owing to the large
      number of potential mimics and should prompt consideration of appropriate
      molecular studies.

PMID- 28756978
TI  - Prognostic significance of lactate dehydrogenase B according to histologic type
      of non-small-cell lung cancer and its association with serum lactate
      dehydrogenase.
AB  - Lactate dehydrogenase B (LDHB) expression and the level of serum LDH were
      involved in tumor progression. Correlations between these parameters and their
      prognostic significance were not assessed in non-small cell lung cancer (NSCLC).
      We evaluated LDHB expression by immunohistochemical method and serum LDH in 243
      NSCLC patients treated with surgical resection [136 adenocarcinomas (ADCs), 89
      squamous cell carcinomas (SqCCs) and 18 other type carcinomas]. Correlation
      between LDHB expression and serum LDH was assessed, and the prognostic
      significance was determined. LDHB expression was identified in 52% of SqCC and
      55% of ADC tissue samples. LDHB-positive SqCC patients had a higher recurrence
      free survival (RFS) rate than LDHB-negative patients (p=0.017). LDHB-positive and
      LDHB-negative patients showed similar RFS rates in ADCs (p=0.519). Multivariate
      analysis showed that LDHB expression was an independent risk factor in lung SqCCs
      (hazard ratio=0.393, p=0.028). A positive correlation was found between LDHB
      expression and serum LDH level (p=0.02). High LDHB expression is significantly
      associated with the level of serum LDH and better clinical outcomes in lung SqCC.

PMID- 28756977
TI  - Prognostic value of IMP3 expression as a determinant of chemosensitivity in
      triple-negative breast cancer.
AB  - Triple negative breast cancer (TNBC) has an aggressive phenotype and poor
      prognosis. Neoadjuvant chemotherapy (NAC) is often used to treat TNBC, but some
      patients are resistant to NAC. We postulated that a subpopulation of TNBC cells
      expressing IMP3, an oncofetal protein, could be resistant to NAC, contributing to
      the poor prognosis. We investigated immunohistochemical expression of IMP3 in 42
      TNBC patients who underwent NAC in association with clinical outcomes. The
      patients were divided into IMP3 positive (+) (n=19) and negative (-) (n=23)
      groups. High Ki67 positivity was detected in 13 patients of the IMP3+group and 8
      cases in the IMP3 - group (p=0.03). While 9 patients in the IMP3 - group (39%)
      were responders, the majority of the IMP3+patients (84.2%) were non-responders
      (p=0.01). In a Cox proportional hazard model, IMP3 expression was independently
      associated with poor NAC response and clinical outcomes (p=0.03 and 0.046,
      respectively). The IMP3+group showed a tendency toward shorter overall survival
      compared to the IMP3 - group with marginal significance (p=0.07). These findings
      suggest that IMP3+tumor cells contributed to the poor clinical outcomes by
      exerting a chemoresistance to NAC, and that IMP3 expression has prognostic value
      as a biomarker for chemosensitivity and overall survival in TNBC.

PMID- 28756979
TI  - Thymosin beta-4 overexpression correlates with high-risk groups in gastric
      gastrointestinal stromal tumors: A retrospective analysis by
      immunohistochemistry.
AB  - BACKGROUND: Thymosin beta-4 (Tbeta4) is a protein that is linked to a number of
      important biological actions and recently tumor progression and poor prognosis of
      some tumors. The aim of this study was to evaluate Tbeta4 expression in gastric
      GISTs and correlate with some clinicopathological characteristics related with
      prognosis and clinical outcome in order to add further data to the current
      literature. METHODS: Tbeta4 antibody was applied to the 4MUm-thick paraffin
      sections of 57 gastric GISTs by immunohistochemistry. RESULTS: Tbeta4 expression
      was found to be directly corrrelated with higher risk groups, tumor size, mitotic
      count, cellularity, and necrosis while it was inversely correlated with overall
      survival (OS) by univariate analysis (p=0.000, p=0.001, p=0.000, p=0.025,
      p=0.023, and p=0.042, respectively). The direct association between Tbeta4
      expression and risk groups were also supported by multivariate analysis (p=0.000,
      beta=0.497, t=4.374). CONCLUSION: Overexpression of Tbeta4 was found to be
      related with predictive characteristics for tumor progression and adverse
      prognosis. Thus, we suggest that overexpression of Tbeta4 might play a role in
      the progression of gastric GISTs and might be used as a potential prognostic tool
      as well as a target for novel therapies.

PMID- 28756980
TI  - PKC-delta attenuates the cancer stem cell among squamous cell carcinoma cells
      through down-regulating p63.
AB  - Protein kinase C delta (PKC-delta) has been identified as a tumor suppressor.
      However, the effects of PKC-delta on the cancer stem cells in squamous cell
      carcinomas (SCC) have not been clarified. The purpose of this study was to detect
      the regulation of PKC-delta on cancer stem cell among SSC cells and the role of
      p63 during the regulation. Immunohistochemistry of human cutaneous SCC tissues
      was performed to detect the expression of PKC-delta. After the human SCC13 cells
      infected by recombinant adenoviruses, the cell proliferation were determined. The
      correlation of PKC-delta and p63 was detected by western blot. The colony forming
      activity and the number of cancer stem cells (CSCs) in SCC identified by double
      staining with anti-integrin alpha6 and anti-CD71 antibodies were detected. The
      expression of PKC-delta was obviously decreased in SCC tissues compared with that
      in normal skin tissues. The higher protein level of p63 in SCC was attenuated by
      the transfection of PKC-delta. The higher proliferation capacity of SCC13 cells,
      the higher activity and expression of CSCs in SCC13 cells induced by p63 were
      significantly suppressed by the transfection of PKC-delta. In conclusion, PKC
      delta played as a protective role in SCC partly by down-regulating p63, leading
      to the suppression of SCC cell proliferation, attenuation of the activity and
      expression of CSCs in SCC cells.

PMID- 28756981
TI  - Congenital undifferentiated sarcoma associated to BCOR-CCNB3 gene fusion.
AB  - Small round cell sarcomas are aggressive bone and soft tissue tumors that
      predominantly affect children and young adults. A new group of sarcomas with a
      recurrent BCOR-CCNB3 gene fusion has been recently identified in previously
      unclassifiable small round cell sarcomas. BCOR-CCNB3 sarcomas share clinical and
      pathologic similarities with Ewing sarcoma, but show a stronger male predilection
      and less aggressiveness, as well as distinct gene expression profiling and
      pangenomic SNP array analyses. We report the unusual case of a congenital BCOR
      CCNB3 retroperitoneal sarcoma in a female born at 34th gestational week, which
      was diagnosed in necropsy after 21hours of life. Immunohistochemical analysis
      showed diffuse expression of CD99 and CCNB3. SNPa showed two focal segmentary
      deletions at 5q34 and 22q11.23, the latter harboring among others the
      SMARCB1/INI1 tumor suppressor gene. Immunohistochemistry confirmed loss of INI1
      in tumor cells, which has not been previously reported in this type of
      undifferentiated sarcomas.

PMID- 28756982
TI  - A meta-analysis of the relationship between ataxia-telangiectasia mutated gene
      polymorphisms and lung cancer susceptibility.
AB  - PURPOSE: This study aimed to analyze the relationship between ataxia
      telangiectasia mutated (ATM) gene polymorphisms and lung cancer susceptibility
      using a meta-analysis. METHODS: A literature search of the PubMed and EMBASE
      databases was performed using keywords such as "ATM gene" and "lung cancer," and
      the deadline "October 15 (th), 2016." After extracting relevant details, each
      selected literature was evaluated for quality according to the Newcastle-Ottawa
      Scale (NOS) scores, and Hardy-Weinberg equilibrium and heterogeneity tests were
      performed. Odds ratios (ORs) and 95% confidence interval (CI) were evaluated
      using R 3.12 software. RESULTS: Eight eligible studies, published from 2004 to
      2013, were identified. The NOS scores of these ranged from 5 to 7. The allele
      genetic model (OR=1.15; 95% CI, 1.01-1.31); additive genetic model (OR=1.44; 95%
      CI, 1.09-1.90); recessive genetic model (OR=1.48; 95% CI, 1.16-1.88); and
      dominant genetic model (OR=1.50; 95% CI, 1.16-1.93) of rs664143 (A>G) were found
      to be significantly different. For rs664677 (C>T), significant differences were
      found in the additive genetic model (OR=1.26, 95% CI, 1.01-1.55) and recessive
      genetic model (OR=1.31; 95% CI, 1.09-1.57). However, the other 2 genetic models
      (rs609429, rs664982) did not show significant differences. CONCLUSION: The
      polymorphisms rs664143 and rs664677 of ATM are associated with lung cancer
      occurrence.

PMID- 28756984
TI  - A 55-year-old female with leukoencephalopathy with cerebral calcifications and
      cysts: Case report and radiopathologic description.
AB  - Adult-onset leukoencephalopathies with increased cerebral volume can present a
      potentially challenging diagnosis for the pathologist. We present the case of a
      patient with a rare adult-onset disease called Leukoencephalopathy with cerebral
      Calcifications and Cysts (LCC). A 55-year-old woman with a history of morning
      headaches, mild memory loss, diabetes, and hypertension presented to the
      emergency department with acute onset altered mental status. CT scan revealed
      multiple small hypodense lesions in the white matter with calcifications in the
      bilateral cerebral hemispheres, basal ganglia, pons, and cerebellar hemispheres.
      MRI showed multiple complex/hemorrhagic cystic lesions with partial enhancement
      in addition to calcifications bilaterally in the frontotemporal white matter,
      pons, and cerebellar hemispheres, and diffuse white matter signal abnormality.
      The differential diagnosis included chronic infection, chronic thromboembolic
      disease, and neoplasm. The biopsy revealed extensive geode-like mineralization as
      well as smaller calcifications (calcospherites) with associated sclerosis,
      Rosenthal fibers, angiomatous proliferation of blood vessels with thrombosis and
      microbleeds. We discuss the differential diagnosis, radiologic and detailed
      histologic features of LCC.

PMID- 28756983
TI  - Morphological characteristics of fatal pediatric hand, foot and mouth disease: A
      clinicopathological study with related receptors of EV71.
AB  - OBJECTIVE: To investigate the pathological features of fatal pediatric hand foot
      and mouth disease (HFMD). METHODS: The histopathological features of HFMD were
      first summarized from literature, and then confirmed by in-house autopsies.
      Furthermore, immunohistochemistry was conducted to detect the distribution and
      expression level of two enterovirus 71 (EV71) receptors scavenger receptor class
      B, member 2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL1) in the samples
      of autopsies. RESULTS: The main symptoms of HFMD included hand and foot rashes,
      as well as oral herpes. The fatal HFMD patients had typical histopathological
      change in the central nervous system, such as encephaledema and encephalitis. As
      for respiratory system, the fatal HFMD patients suffered acute pulmonary edema
      and congestion. SCARB2 positive signaling was distributed equally in bronchial
      and bronchiolar epithelial cells, alveolar epithelial cells and inflammatory
      cells of all HFMD patients, healthy children and adults without significant
      difference. PSGL-1 dispersed in bronchial and bronchiolar epithelial cells of
      healthy adults, but no PSGL-1 expression was detected in HFMD patients and
      healthy children. CONCLUSIONS: Both of the central nervous and respiratory
      systems may be involved in the fatal HFMD patients. The EV71 receptor PSGL-1
      might play essential parts in the pathogenesis of fatal HFMD, however, the
      hypothesis needs to be further investigated.

PMID- 28756985
TI  - Concomitant Epstein-Barr Virus-associated smooth muscle tumor and granulomatous
      inflammation of the liver.
AB  - Epstein-Barr Virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal
      tumor typically seen in immunocompromised patients. Here, we report a case of EBV
      SMT and associated granulomatous inflammation in the liver of a 32-year-old man
      with history of human immunodeficiency virus/acquired immune deficiency syndrome
      (HIV/AIDS). To our knowledge, an association of these two lesions has not been
      previously reported. We review the literature and discuss pathogenesis,
      differential diagnosis and immunohistochemical (IHC) stains helpful for the
      diagnosis of this rare entity. Finally, we consider possible explanations for the
      concomitant presence of these lesions.

PMID- 28756986
TI  - Extraskeletal aneurysmal bone cyst: Report of a case and review of the
      literature.
AB  - Aneurysmal bone cyst (ABC) is an expansile cystic lesion that may affect any bone
      of the skeleton. Although exceedingly rare, lesions with histomorphologic
      characteristics of an ABC have reportedly originated within soft tissue.
      Extraskeletal ABC may mimic a variety of benign and malignant lesions and can be
      confused with other more common or rare giant cell-rich tumors of soft tissue,
      especially myositis ossificans. Clinical, radiological and histologic correlation
      is crucial in reaching the correct diagnosis. Cytogenetic and/or molecular
      genetic analysis is a useful adjunct in diagnosing these exquisitely rare
      lesions. Here we report a case of an ABC arising in an extraskeletal site and
      provide a comprehensive review of literature on this rare entity.

PMID- 28756987
TI  - Prevalence of protein C receptor (PROCR) is associated with inferior clinical
      outcome in Breast invasive ductal carcinoma.
AB  - Recently, PROCR is reported to play an important role in cell growth, apoptosis,
      proliferation and tumor relapse. Some researchers thought that PROCR+ cells had
      cancer stem cell ability, which might contribute to progressive behavior in
      breast cancer. Our study was to assess the expression of PROCR in invasive ductal
      carcinoma tissues with their prognostic implications. We enrolled formalin fixed
      paraffin-embedded tumor tissues of 271 patients diagnosed as invasive ductal
      breast cancer with clinical stage II or III into our study. Immunohistochemistry
      staining was performed on all the tissue microarray slides, and result were
      interpreted by two pathologists with blinded method. We analyzed PROCR expression
      levels with the clinical characteristics as well as their prognostic values.
      PROCR expression detected in the cell was interpreted. Chi-square test showed us
      its positive expression had a close association with distant metastases
      (p=0.035). Univariate survival analysis indicated that prevalence of PROCR
      expression in the invasive ductal breast cancer was significantly related with
      decreased disease-free survival (pDFS=0.010) and overall survival (pOS=0.008). In
      multivariate survival by Cox proportional hazard model, positive expression group
      for PROCR was found to have shorter DFS [pDFS=0.028, hazard ratio (95% CI):
      1.183(1.069-3.140)]. Our findings suggested that breast cancer patients with
      expression of PROCR is more prone to suffer from distant metastasis and bad
      clinical outcomes.

PMID- 28756988
TI  - Tissue hemostasis is shifted toward thrombogenesis in the psoriatic plaques.
AB  - BACKGROUND: Psoriasis is a common autoimmune disease of unknown etiology.
      Recently, much attention has been paid to evidence that a local hypercoagulable
      state is an important contributing factor to the development of inflammatory skin
      diseases. Thus, the aim of this study was to characterize the local hemostasis in
      the affected skin of patients with psoriasis. METHODS: Skin biopsies of psoriatic
      plaques were obtained from 73 consecutive patients (48M, 25F, average age 45
      years) with at least a one year history of the disease. The studied patients had
      not received any specific systemic treatment for at least 4 weeks before the
      biopsy was done. As a control, normal skin biopsies were obtained from 16 healthy
      subjects. For immunohistological study, the En-Vision method (DAKO EnVision Kit
      (r)/Alkaline Phosphatase detection system), and monoclonal antibodies anti-tissue
      factor (TF), anti-thrombomodulin (TM) and anti-von Willebrand Factor (vWF) were
      used. All these molecules were assessed semi-quantitatively in the frozen
      sections. RESULTS: Clinically, the Body Surface Area index ranged between 1-90%
      and the Psoriasis Area Severity Index score ranged from 1.6 to 47.
      Immunohistochemistry revealed redistribution of TF antigens from the upper to
      lower layers of the epidermis as compared to the control. It was collaborated
      with the number of TF-positive cells in the psoriatic skin sections (78.3%) as
      compared with the healthy subjects (34.4%; P<0.001). In addition, TF was
      uniformly and moderately expressed on capillary endothelial cells of the plaque
      sections in 43 out of 73 patients (58.9%). As far as the thrombomodulin is
      concerned, TM was clearly down-regulated and localized mainly in the upper layers
      of the psoriatic epidermis. It was collaborated with the number of TM positive
      cells in the psoriatic skin sections (38.9%) as compared with the healthy
      subjects (66.7%; P<0.001). All capillary vessels found in the biopsy sections
      were positive for TM and vWF staining, with similar expression (>=2+) in both
      groups. In the current study, no relationship was found between the TF, TM and
      vWF expression and the PASI and BAS (NS). CONCLUSIONS: A local procoagulable
      state found in psoriatic plaques suggests a significant role of local tissue
      hemostasis in pathogenesis of the disease. These findings indicate another
      potential target for a therapeutic approach in patients with psoriasis, although
      further research would help elucidate the exact mechanisms.

PMID- 28756989
TI  - Recent developments in biochar utilization as an additive in organic solid waste
      composting: A review.
AB  - In recent years, considerable studies have been devoted to investigating the
      effect of biochar application on organic solid waste composting. This review
      provides an up-to-date overview of biochar amendment on composting processes and
      compost quality. Biochar production, characteristics, and its application coupled
      with the basic concepts of composting are briefly introduced before detailing the
      effects of biochar addition on composting. According to recent studies, biochar
      has exhibited great potential for enhancing composting. It is evident that
      biochar addition in composting can: (1) improve compost mixture physicochemical
      properties, (2) enhance microbial activities and promote organic matter
      decomposition, (3) reduce ammonia (NH3) and greenhouse gas (GHG) emissions, and
      (4) upgrade compost quality by increasing the total/available nutrient content,
      enhancing maturity, and decreasing phytotoxicity. Despite that, further research
      is needed to explore the mechanism of biochar addition on composting and to
      evaluate the agricultural and environmental performances of co-composted biochar
      compost.

PMID- 28756990
TI  - Thermal stability of biochar and its effects on cadmium sorption capacity.
AB  - In this study, the thermal stability of a wood shaving biochar (WS, 650 degrees
      C), a chicken litter biochar (CL, 550 degrees C) and an activated carbon (AC,
      1100 degrees C) were evaluated by combustion at 375 degrees C for 24h to remove
      the labile non-carbonized organic matter. Results showed that WS and CL biochars
      were not thermally stable and can lose most of the organic C during combustion.
      The combusted WS and CL biochars retained considerable amounts of negative charge
      and displayed higher sorption for Cd (from 5.46 to 68.9mg/g for WS and from 48.5
      to 60.9mg/g for CL). The AC retained 76.5% of its original C and became more
      negatively chargely after combustion, but its sorption for Cd slightly decreased
      (from 18.5 to 14.9mg/g). This study indicated that after potential burning in
      wildfires (200-500 degrees C), biochars could have higher sorption capacity for
      metals by remaining minerals.

PMID- 28756991
TI  - Nutritional Status of Breast Cancer Survivors 1 Year after Diagnosis: A
      Preliminary Analysis from the Malaysian Breast Cancer Survivorship Cohort Study.
AB  - BACKGROUND: Lifestyle factors, such as diet, body weight, and physical activity,
      are linked to better survival after breast cancer (BC) diagnosis. A high
      percentage of the Malaysian population is overweight or obese. In addition,
      studies have shown a disparity in survival among Malaysian women compared with
      other higher-income countries. The Malaysian Breast Cancer Survivorship Cohort
      (MyBCC) study aims to study lifestyle factors that affect survival in BC
      survivors. These are the preliminary findings on the nutritional status of
      Malaysian BC survivors. OBJECTIVE: Our aim was to evaluate the nutritional status
      of BC survivors at 1 year after diagnosis. DESIGN: This was a cross-sectional
      study of 194 participants from the MyBCC study, recruited within 1 year of their
      diagnosis. Participants completed a 3-day food diary. PARTICIPANTS: Malaysian
      women (aged 18 years and older) who were newly diagnosed with primary BC, managed
      at the University Malaya Medical Center, and able to converse either in Malay,
      English, or Mandarin were included. MAIN OUTCOME MEASURES: Dietary intake and
      prevalence of overweight or obesity among participants 1 year after diagnosis
      were measured. STATISTICAL ANALYSES PERFORMED: Student's t test and analysis of
      variance or its equivalent nonparametric test were used for association in
      continuous variables. RESULTS: About 66% (n=129) of participants were overweight
      or obese and >45% (n=86) had high body fat percentage 1 year after diagnosis. The
      participants' diets were low in fiber (median=8.7 g/day; interquartile range=7.2
      g/day) and calcium (median=458 mg/day; interquartile range=252 mg/day). Ethnicity
      and educational attainment contributed to the differences in dietary intake among
      participants. Higher saturated fat and lower fiber intake were observed among
      Malay participants compared with other ethnic groups. CONCLUSIONS: Overweight and
      obesity were highly prevalent among BC survivors and suboptimal dietary intake
      was observed. Provision of an individualized medical nutrition therapy by a
      qualified dietitian is crucial as part of comprehensive BC survivorship care.

PMID- 28756992
TI  - Structural and evolutionary aspects of algal blue light receptors of the
      cryptochrome and aureochrome type.
AB  - Blue-light reception plays a pivotal role for algae to adapt to changing
      environmental conditions. In this review we summarize the current structural and
      mechanistic knowledge about flavin-dependent algal photoreceptors. We especially
      focus on the cryptochrome and aureochrome type photoreceptors in the context of
      their evolutionary divergence. Despite similar photochemical characteristics to
      orthologous photoreceptors from higher plants and animals the algal blue-light
      photoreceptors have developed a set of unique structural and mechanistic features
      that are summarized below.

PMID- 28756993
TI  - Conditional Selection of Genomic Alterations Dictates Cancer Evolution and
      Oncogenic Dependencies.
AB  - Cancer evolves through the emergence and selection of molecular alterations.
      Cancer genome profiling has revealed that specific events are more or less likely
      to be co-selected, suggesting that the selection of one event depends on the
      others. However, the nature of these evolutionary dependencies and their impact
      remain unclear. Here, we designed SELECT, an algorithmic approach to
      systematically identify evolutionary dependencies from alteration patterns. By
      analyzing 6,456 genomes from multiple tumor types, we constructed a map of
      oncogenic dependencies associated with cellular pathways, transcriptional
      readouts, and therapeutic response. Finally, modeling of cancer evolution shows
      that alteration dependencies emerge only under conditional selection. These
      results provide a framework for the design of strategies to predict cancer
      progression and therapeutic response.

PMID- 28756994
TI  - Dual-Energy X-ray Absorptiometry Predictors of Vertebral Deformities in Beta
      Thalassemia Major.
AB  - Vertebral fractures in beta-thalassemia major are increasingly found because of
      the longer life expectancy of patients, with a major negative impact on their
      quality of life. We performed a retrospective cross-sectional study to
      investigate the prevalence of vertebral deformities in thalassemic patients and
      to identify their best dual-energy X-ray absorptiometry (DXA) predictor among
      trabecular bone score (TBS), bone mineral density (BMD), and Z-score. Eighty-two
      outpatients with beta-thalassemia major on regular conventional treatment were
      studied at a single academic center. All patients underwent plain thoracic-lumbar
      spine X-rays and lumbar DXA to assess the number and the severity of vertebral
      deformities (Genant's method), the spinal deformity index, lumbar spine DXA
      parameters (BMD, TBS, and Z-score), and the presence of platyspondyly. Twenty
      nine patients (35%) had vertebral deformities and showed significantly lower TBSs
      than the remainders (1.141 +/- 0.083 vs 1.254 +/- 0.072, p < 0.0001). The
      analysis of variance of the TBS between the group of patients without vertebral
      deformities (spinal deformity index = 0) and the remaining groups showed a
      significant difference (p < 0.001). The TBS had better sensitivity (86.2%),
      specificity (75.5%), and diagnostic accuracy (79.3%) than BMD and Z-score in
      discriminating patients with and without vertebral deformities. Combining the TBS
      with the BMD or the Z-score showed that the diagnostic accuracy of the first in
      discriminating patients with and without vertebral deformities improved from
      79.3% to 85.4% and 87.8%, respectively. The presence of platyspondyly was a
      significant predictor of vertebral deformities in the multivariate model.
      Vertebral deformities in well-treated patients with beta-thalassemia major are
      common and are often unrecognized. In our hands, the TBS was better than the BMD
      and the Z-score in predicting vertebral deformities. Plain X-rays of the spine
      should be performed also in asymptomatic patients, especially when the TBS is
      low.

PMID- 28756995
TI  - An Investigation Into the Differences in Bone Density and Body Composition
      Measurements Between 2 GE Lunar Densitometers and Their Comparison to a 4
      Component Model.
AB  - We describe a study to assess the precision of the GE Lunar iDXA and the
      agreement between the iDXA and GE Lunar Prodigy densitometers for the measurement
      of regional- and total-body bone and body composition in normal to obese healthy
      adults. We compare the whole-body fat mass by dual-energy X-ray absorptiometry
      (DXA) to measurements by a 4-component (4-C) model. Sixty-nine participants, aged
      37 +/- 12 yr, with a body mass index of 26.2 +/- 5.1 kg/cm2, were measured once
      on the Prodigy and twice on the iDXA. The 4-C model estimated fat mass from body
      mass, total body water by deuterium dilution, body volume by air displacement
      plethysmography, and bone mass by DXA. Agreements between measurements made on
      the 2 instruments and by the 4-C model were analyzed by Bland-Altman and linear
      regression analyses. Where appropriate, translational cross-calibration equations
      were derived. Differences between DXA software versions were investigated. iDXA
      precision was less than 2% of the measured value for all regional- and whole-body
      bone and body composition measurements with the exception of arm fat mass
      (2.28%). We found significant differences between iDXA and Prodigy (p < 0.05)
      whole-body and regional bone, fat mass (FM), and lean mass, with the exception of
      hip bone mass, area and density, and spine area. Compared to iDXA, Prodigy
      overestimated FM and underestimated lean mass. However, compared to 4-C, iDXA
      showed a smaller bias and narrower limits of agreement than Prodigy. No
      significant differences between software versions in FM estimations existed. Our
      results demonstrate excellent iDXA precision. However, significant differences
      exist between the 2 GE Lunar instruments, Prodigy and iDXA measurement values. A
      divergence from the reference 4-C observations remains in FM estimations made by
      DXA even following the recent advances in technology. Further studies are
      particularly warranted in individuals with large FM contents.

PMID- 28756996
TI  - Importance of arterial stiffness as a cardiovascular risk factor.

PMID- 28756997
TI  - Treatment of oral lichen planus. Systematic review and therapeutic guide.
AB  - In this systematic review, 55 structured articles on the therapeutic efficacy
      against pain and clinical signs of oral lichen planus (OLP) were analysed. The
      literature search was developed according to the criteria of the PRISMA system,
      selecting the tests performed using one of the following methodological designs:
      drug (active ingredient) vs. drug in different excipient or concentration, drug
      vs. different active principle, drug vs. phytotherapy and drug vs. treatment with
      phototherapy. Based on the results, an algorithm is proposed to guide the
      treatment of OLP in its atrophic and erosive clinical forms. The use of
      clobetasol propionate at 0.025-0.05% of topical application as the first
      therapeutic alternative is highlighted. Secondly, 0.1% tacrolimus and 1%
      pimecrolimus also formulated for its topical regimen. And finally, we address the
      use of systemic corticosteroids and the application of diode lasers.

PMID- 28756998
TI  - Effectiveness of Infliximab in colchicine resistant familial Mediterranean fever.

PMID- 28756999
TI  - Outbreak of botulism due to consumption of beans.

PMID- 28757000
TI  - Characteristics of Vitamin B12 Deficiency in Patients With Plasma Cell Disorders.
AB  - BACKGROUND: Although increased rates of vitamin B12 deficiency have been reported
      in patients with plasma cell dyscrasias (PCDs), no mechanism has been identified.
      Excess free light chains (FLCs) could disrupt the renal proximal tubule receptors
      where B12 is reabsorbed. We sought to characterize the relationship between B12
      deficiency and PCDs. We hypothesized that rates of B12 deficiency would be
      highest in patients with PCDs with high FLC burdens. METHODS: We reviewed the
      electronic medical records of 501 patients who met inclusion criteria (diagnosed
      PCD with documented serum B12 and FLC levels) to obtain clinical data recorded
      prior to patients' lowest B12 levels. RESULTS: Overall, 20.0% of patients had low
      vitamin B12. There was an expected negative correlation between estimated
      glomular filtration rate and FLC (rs = -0.317; P < .001). However, low B12 levels
      were more prevalent in patients with preserved renal function (P = .047). Low B12
      was associated with lower mean corpuscular volume (P = .037). CONCLUSION: Higher
      FLC burden was associated with poor kidney function but not with low B12. Low B12
      was seen more commonly in patients with preserved kidney function. Mean
      corpuscular volume was statistically but not clinically different between
      patients with low and normal B12 and, therefore, may not be a reliable indicator
      of B12 deficiency in PCDs. Prospective studies should compare B12 metabolites
      with FLC levels. Detection of B12 deficiency among patients with PCDs remains
      important to reduce neurologic dysfunction and cytopenias, sequelae common to B12
      deficiency and PCDs.

PMID- 28757001
TI  - Spinal muscular atrophy: A changing phenotype beyond the clinical trials.
AB  - Spinal muscular atrophy is a monogenic, progressive motor neuron disorder caused
      by deletion or mutation in the SMN1 gene. A broad range of phenotypic severity,
      from very weak infants (Type 1) to ambulant children (type 3), is modified mainly
      by the number of copies of the "backup" SMN2 gene. Since the discovery of the
      role of both genes, basic research into the pathobiology of SMA, with in vitro
      and animal model studies, has identified therapeutic targets. Development of
      clinical outcome measures, natural history studies and standard of care
      guidelines have contributed to the development of protocols for therapeutic drugs
      now under clinical investigation. Following regulatory approval of the first drug
      treatment for SMA in the US (December, 2016) and marketing authorization in
      Europe (June, 2017), the prospects for care of these patients have changed. The
      evolution of the phenotype of SMA now needs to be considered beyond the clinical
      trials. This perspective review discusses potential new trajectories in the
      phenotype of SMA and the need for multidisciplinary teams to prepare for this
      changing landscape.

PMID- 28757002
TI  - Narrative construction is intact in episodic amnesia.
AB  - Autobiographical remembering and future imagining overlap in their underlying
      psychological and neurological mechanisms. The hippocampus and surrounding
      regions within the medial temporal lobes (MTL), known for their role in forming
      and maintaining autobiographical episodic memories, are also thought to play an
      essential role in fictitious and future constructions. Amnesic individuals with
      bilateral hippocampal damage cannot reconstruct their past personal experiences
      and also have severe deficits in the ability to construct coherent fictitious or
      future narratives. However, it is not known whether this impairment reflects a
      failure to generate details from autobiographical episodic memory to populate
      personal narratives or an inability to bind such details into coherent
      narratives. We show that four individuals with hippocampal damage and episodic
      amnesia can construct narratives when the relevant details of the story are
      provided in a picture book and that their narratives maintain overall coherence
      on several measures. These findings indicate that individuals with hippocampal
      damage can bind details into coherent narratives when details are available to
      them. We conclude that the hippocampal system instead likely plays a role in the
      generation of details from which narratives are constructed.

PMID- 28757003
TI  - Transcranial direct current stimulation (tDCS) modulation of picture naming and
      word reading: A meta-analysis of single session tDCS applied to healthy
      participants.
AB  - Recent reviews quantifying the effects of single sessions of transcranial direct
      current stimulation (or tDCS) in healthy volunteers find only minor effects on
      cognition despite the popularity of this technique. Here, we wanted to quantify
      the effects of tDCS on language production tasks that measure word reading and
      picture naming. We reviewed 14 papers measuring tDCS effects across a total of 96
      conditions to a) quantify effects of conventional stimulation on language regions
      (i.e., left hemisphere anodal tDCS administered to temporal/frontal areas) under
      normal conditions or under conditions of cognitive (semantic) interference; b)
      identify parameters which may moderate the size of the tDCS effect within
      conventional stimulation protocols (e.g., online vs offline, high vs. low current
      densities, and short vs. long durations), as well as within types of stimulation
      not typically explored by previous reviews (i.e., right hemisphere anodal tDCS or
      left/right hemisphere cathodal tDCS). In all analyses there was no significant
      effect of tDCS, but we did find a small but significant effect of time and
      duration of stimulation with stronger effects for offline stimulation and for
      shorter durations (< 15min). We also found some indication of publication bias
      towards reporting positive effects. We encourage further experimentation in order
      resolve the disparity between the current popularity of tDCS and its poor
      efficacy in healthy participants.

PMID- 28757004
TI  - Corrigendum to "Genome-wide association interaction analysis for Alzheimer's
      disease." [Neurobiol. Aging 35 (2014) 2436-2443].

PMID- 28757005
TI  - Kerion Celsi with erythematous tumefaction on the groin due to Trichophyton
      mentagrophytes.

PMID- 28757006
TI  - [Pulmonary mucormycosis in a patient with kidney transplant and uncontrolled
      haemoptysis].
AB  - BACKGROUND: Pulmonary mucormycosis is a rare opportunistic infection with high
      mortality that is caused by species of Mucorales. The most common species
      involved are Rhizopus, Mucor, Lichtheimia, and Rhizomucor. CASE REPORT: A 56 year
      old woman presented with a clinical history of diabetes mellitus type 2 and
      chronic renal disease. She underwent a cadaveric kidney transplantation two years
      before her admission, for which immunomodulating therapy with thymoglobulin,
      tacrolimus, mofetil-microphenolate and prednisone was established. The patient
      suffered a pneumonic process with cough, expectoration, and dyspnoea. The
      computed tomography scan showed a cavitation in the right upper lobe. With all
      these findings an invasive broncopulmonary aspergillosis was suspected and the
      patient began an antifungal treatment with voriconazole without improvement.
      Rhizomucor pusillus was isolated from a clinical specimen obtained by fine needle
      aspiration, and its identification was confirmed by PCR. After this finding
      amphotericin B was administered, but the patient had an uncontrolled haemoptysis
      and died. CONCLUSIONS: Pulmonary mucormycosis is a rare infection, usually fatal
      in kidney transplant recipients with anti-rejection therapy. Mucorales species
      usually produce thrombotic phenomena, associated with necrosis and parenchymal
      destruction that caused a fatal uncontrolled haemoptysis in our patient. Early
      diagnosis is important in order to perform any surgical treatment and to
      administer amphotericin B.

PMID- 28757007
TI  - Different susceptibility and pathogenesis of rabbit genotype 3 hepatitis E virus
      (HEV-3) and human HEV-3 (JRC-HE3) in SPF rabbits.
AB  - Hepatitis E virus (HEV) is an increasingly important zoonotic infection in humans
      with HEV genotypes 3 and 4 being recognized as zoonotic pathogens. The relatively
      recently isolated genotype 3 rabbit HEV (rHEV-3) and the more well known genotype
      3 isolates from humans and swine (hsHEV-3) have all been confirmed experimentally
      to be capable of infecting both non-human primates and specific-pathogen free
      (SPF) pigs. In a previous study rHEV-3 was shown to cause acute hepatitis in
      experimentally infected rabbits. However, whether hsHEV-3 can productively infect
      rabbits remained unclear. The objective of this study was to investigate the
      experimental infection of rabbits with human HEV-3 (hHEV-3, JRC-HE3), to compare
      it to that with rHEV-3 (CHN-BJ-rb14) and to further characterise the pathogenesis
      of the two isolates. All animals inoculated with rHEV-3 (CHN-BJ-rb14) became
      infected, exhibiting an intermittent viremia, elevated liver enzymes, and
      persistent fecal virus shedding throughout the 15 week study period. Liver
      histopathology showed acute inflammation and both positive- and negative-stranded
      viral RNA was detected in various tissues from necropsied rabbits. By contrast,
      neither sero-conversion nor alanine aminotransferase (ALT) elevation was observed
      in most rabbits inoculated with hHEV-3 (JRC-HE3). In addition, rHEV-3 (CHN-BJ
      rb14) but not hHEV-3 (JRC-HE3) recovered from primary infected rabbits was
      transmissible to naive rabbits. These results showed that SPF rabbits are readily
      susceptible to infection with rHEV-3 (CHN-BJ-rb14) but not hHEV-3 (JRC-HE3),
      which might indicate the influence of viral genomic organization on its
      pathogenicity.

PMID- 28757008
TI  - High occurrence of mecC-MRSA in wild hedgehogs (Erinaceus europaeus) in Sweden.
AB  - We investigated the occurrence of mecC-MRSA in wild hedgehogs (Erinaceus
      europaeus) in Sweden and characterized the obtained isolates. Samples from 55
      hedgehogs from five counties of Sweden were cultivated selectively for MRSA and
      putative isolates were confirmed by real-time PCR detecting mecA, mecC, nuc and
      PVL genes. mecC-MRSA was confirmed in 35 (64%) animals from three geographically
      separated counties. Confirmed isolates were spa-typed and tested for
      antimicrobial susceptibility by broth microdilution. Eight different spa-types
      were identified (t843, t978, t3391, t9111, t10751, t10893, t11015, t15312) of
      which t843 (49%) was the most common. The spa-types t843, t3391 and t978 were
      found in isolates from two counties. The study shows that mecC-MRSA is common in
      wild hedgehogs in two counties of Sweden but occurs in hedgehogs also in other
      parts of the country. Our findings suggest that hedgehogs could be a reservoir
      for mecC-MRSA. In addition, similar spa-types of isolates from hedgehogs and
      isolates previously described in domesticated animals and in humans indicates
      transfer between these populations.

PMID- 28757009
TI  - Efficacy evaluation of three modified-live virus vaccines against a strain of
      porcine reproductive and respiratory syndrome virus NADC30-like.
AB  - Porcine reproductive and respiratory syndrome reproductive virus is a devastating
      pathogen causing tremendous economic losses to swine production worldwide.
      Emergence of novel and variant PRRSV strains always leads to variable protection
      efficacy of modified-live virus (MLV) vaccines. Prevalence of PRRSV NADC30-like
      recently emerging in China has brought about clinical outbreaks of the disease.
      In the present study, the pathogenicity of a NADC30-like strain CHsx1401 for
      piglets was analyzed, and the potential cross-protective efficacy of three MLV
      vaccines including two commercial MLV vaccines and an attenuated low pathogenic
      PRRSV against this virus was further evaluated in piglets. The NADC30-like
      CHsx1401 was shown to cause fever, respiratory clinical signs, and lung gross and
      microscopic lesions of the inoculated piglets, suggesting that this virus is
      moderate virulent for piglets. Vaccination of piglets with the MLV vaccines could
      not reduce the clinical signs and lung lesions, and was partially efficacious in
      the reduction of viral loads in sera upon NADC30-like CHsx1401 challenge,
      indicating that these three MLV vaccines provide extremely limited cross
      protection efficacy against the NADC30-like virus infection. Additionally,
      Ingelvac PRRS MLV appeared to exert some beneficial efficiency in shortening the
      period of clinical fever and in improving the growth performance of the
      challenged pigs. Our findings give valuable guidance for the choice and use of
      PRRSV MLV vaccines to control NADC30-like virus infection in the field.

PMID- 28757010
TI  - Patterns of antimicrobial resistance in Streptococcus suis isolates from pigs
      with or without streptococcal disease in England between 2009 and 2014.
AB  - Antimicrobial resistance in Streptococcus suis, a global zoonotic pathogen of
      pigs, has been mostly studied only in diseased animals using surveys that have
      not evaluated changes over time. We compared patterns of resistance between S.
      suis isolates from clinical cases of disease (CC) and non-clinical case (NCC)
      pigs in England, collected over two discrete periods, 2009-2011 and 2013-2014.
      Minimum inhibitory concentrations (MIC) of 17 antimicrobials (nine classes) were
      determined on 405 S. suis isolates categorised by sampling period and disease
      association to assess changes in resistance over time and association with
      disease. First, isolates were characterized as resistant or susceptible using
      published clinical breakpoints. Second, epidemiological cut-offs (ECOFF) were
      derived from MIC values, and isolates classified as wild type (WT) below the
      ECOFF and non-wild type (NWT) above the ECOFF. Finally, isolate subsets were
      analysed for shifts in MIC distribution. NCC isolates were more resistant than CC
      isolates to cephalosporins, penams, pleuromutilins, potentiated sulphonamides and
      tetracyclines in both study periods. Resistance levels among CC isolates
      increased in 2013-2014 relative to 2009-2011 for antimicrobials including
      aminoglycosides, cephalosporins, fluoroquinolones, pleuromutilins, potentiated
      sulphonamides and tetracyclines. The prevalence of isolates categorised as NWT
      for five or more classes of antimicrobials was greater among NCC than CC isolates
      for both time periods, and increased with time. This study used standardised
      methods to identify significant shifts in antimicrobial resistance phenotypes of
      S. suis isolated from pigs in England, not only over time but also between
      isolates from known clinical cases or disease-free pigs.

PMID- 28757011
TI  - Presence and mechanisms of acquired antimicrobial resistance in Belgian
      Brachyspira hyodysenteriae isolates belonging to different clonal complexes.
AB  - Swine dysentery (SD) is an economically important disease for which antimicrobial
      treatment still occupies an important place to control outbreaks. However,
      acquired antimicrobial resistance is increasingly observed in Brachyspira
      hyodysenteriae. In this study, the Minimal Inhibitory Concentrations (MIC) of six
      antimicrobial compounds for 30 recent Belgian B. hyodysenteriae isolates were
      determined using a broth microdilution method. In addition, relevant regions of
      the 16S rRNA, 23S rRNA and the L3 protein encoding genes were sequenced to reveal
      mutations associated with acquired resistance. Finally, a phylogeny was
      reconstructed using minimal spanning tree analysis of multi locus sequence typing
      of the isolates. For lincomycin, doxycycline, tylosin and tylvalosin, at least
      70% of the isolates did not belong to the wild-type population and were
      considered to have acquired resistance. For valnemulin and tiamulin, this was
      over 50%. In all isolates with acquired resistance to doxycycline, the G1058C
      mutation was present in their 16S rRNA gene. All isolates showing acquired
      resistance to lincomycin and both macrolides displayed the A2058T mutation in
      their 23S rRNA gene. Other mutations in this gene and the N148S mutation in the
      L3 protein were present in both wild-type isolates and isolates considered to
      have acquired resistance. Multi locus sequence analysis revealed a previously
      undescribed clonal complex, with 4 novel sequence types in which the majority of
      isolates showed acquired resistance to all tested antimicrobial products. In
      conclusion, acquired antimicrobial resistance is widespread among Belgian B.
      hyodysenteriae isolates. The emergence of multi-resistant clonal complexes can
      pose a threat to swine industry.

PMID- 28757012
TI  - Longitudinal study of transmission of Escherichia coli from broiler breeders to
      broilers.
AB  - Escherichia coli is of major importance in industrial broiler production as the
      main cause of salpingitis and peritonitis in broiler breeders. Furthermore E.
      coli is the most common cause of first week mortality in broiler chickens. The
      aim of the present study was to investigate the transmission of E. coli, isolated
      from broiler breeders with salpingitis, to the progeny and the possibility of
      subsequent first week mortality. Four parent flocks were followed during the
      whole production period (20-60 weeks) by post mortem and bacteriological
      examination of randomly selected dead birds. Newly hatched chickens from each
      flock were swabbed in the cloaca on four occasions (parent age 30, 40, 50, 60
      weeks) and E. coli was isolated. Causes of first week mortality were determined
      pathologically and bacteriologically. E. coli isolates from parents, newly
      hatched chickens and first week mortality were selected for Pulsed-Field-Gel
      Electrophoresis (PFGE) and Multi-Locus-Sequence-Typing (MLST) to determine their
      clonal relationships. E. coli was the main cause of both salpingitis in parents
      and first week mortality in broilers, and E. coli dominated the bacterial flora
      of the cloaca of newly hatched chickens. PFGE of E. coli showed identical band
      patterns in isolates from the three different sources indicating a transmission
      of E. coli from parent birds to chickens. In conclusion, E. coli isolated from
      salpingitis in broiler parents were found to be transmitted to broilers in which
      some sequence types contributed to the first week mortality.

PMID- 28757013
TI  - A haplotype at intron 8 of PTPRT gene is associated with resistance to Brucella
      infection in Argentinian creole goats.
AB  - Brucellosis is the leading zoonosis on a worldwide scale and constitutes a major
      public health threat in many regions of the world. Several molecular markers
      associated with natural resistance to intracellular bacterial infection have been
      identified. Recently seven single-nucleotide polymorphisms (SNPs) located in the
      PTPRT gene were associated with resistance to Mycobacterium bovis infection in
      cattle. Here, we perform a case-control study to test if polymorphisms at PTPRT
      intron 8 might influence the resistance or susceptibility to Brucella infection
      in goats. DNA samples from 22 seropositive (cases) and 22 seronegative (controls)
      for brucellosis, unrelated female creole goats, were included in the present
      study. Four previously reported polymorphisms (SNP1: rs643551276, SNP2:
      rs651618967, SNP3: rs662137815 and SNP4: rs657542977) and a new SNP (SNP5: chr13:
      691695526) were detected by PCR-DNA sequencing method. Genotypic and allelic
      frequencies differed significantly between cases and controls at SNPs 1, 2, 4 and
      5 (p<=0.001). Indeed, the SNP1 TT, SNP2 TT, SNP4 CC and SNP5 TT genotypes were
      associated with absence of Brucella-specific antibodies (ORs=0.019 to 0.045).
      Moreover, haplotype association analysis revealed a significant association of
      the TTCCT haplotype with protection to Brucella infection (p<=1*10-4; OR=18),
      including the major allelic variants associated with resistance. These results
      represent the first evidence of genetic association between polymorphisms in the
      PTPRT gene and absence of brucellosis in goats.

PMID- 28757014
TI  - An in vitro model for assessing effective scrapie decontamination.
AB  - Scrapie infectivity enters the environment via a multiplicity of routes from
      infected animals. Environmentally associated scrapie persists on farms when
      infected animals have been removed and is particularly resistant to disinfection.
      Infectivity within the farm is not adequately removed by current recommended
      guidelines for farm decontamination. We describe an in vitro method for modelling
      decontamination, specifically the removal of scrapie prions from the surface of
      concrete fomites within buildings that have housed scrapie infected animals.
      Concrete that had been spiked with low amounts of a diluted scrapie positive
      brain homogenate was sampled before and after decontamination. Extracts were used
      to seed a semi-quantitative serial protein misfolding cyclic amplification assay
      (sPMCA). We demonstrate that methods currently recommended for prion
      decontamination result in inadequate reduction of prion seeding activity within
      this in vitro assay. Effective treatment was achieved using repeat dosing of
      surfaces with 20,000ppm available chlorine for 4h.

PMID- 28757015
TI  - Dual infections of CD163 expressing NPTr epithelial cells with influenza A virus
      and PRRSV.
AB  - In the pig, respiratory co-infections involving various pathogens are far more
      frequent than single infections. Amongst respiratory viruses, swine influenza
      type A virus (swIAV) and porcine reproductive and respiratory syndrome virus
      (PRRSV) are frequently associated. Previously, we performed co-infections with
      swIAV and PRRSV in porcine alveolar macrophages (PAM) and precision cut lung
      slices (PCLS). With these two approaches it was practically impossible to have co
      infections of the same cells as the main target cell of swIAV is the epithelial
      cell while the main target of PRRSV is the PAM. This constraint makes the study
      of interference between the two viruses difficult at the cellular level. In the
      current report, an epithelial cell line expressing, CD163, the main receptor of
      PRRSV was generated. This cell line receptive for both viruses was used to assess
      the interference between the two viruses. Results showed that swIAV as well as
      PRRSV, even if they interacted differently with the modified epithelial cells,
      were clearly interfering with each other regarding their replication when they
      infected a same cell with consequences within the cellular antiviral response.
      Our modified cell line, receptive to both viruses, can be used as a tool to
      assess interference between swIAV and PRRSV in a same cell as it probably happens
      in the porcine host.

PMID- 28757017
TI  - Characterization of NDM-5-positive extensively resistant Escherichia coli
      isolates from dairy cows.
AB  - The aim of this study was to investigate the prevalence of blaNDM-5 gene in
      Escherichia coli isolates from dairy cows and to characterize the molecular
      traits of the blaNDM-5-positive isolates. A total of 169 cows were sampled (169
      feces and 169 raw milk samples) in three dairy farms in Jiangsu Province and 203
      E. coli isolates were recovered. Among these strains, three isolates carried
      blaNDM-5 gene, including one co-harboring mcr-1, which belonged to sequence type
      446 and the other two belonged to ST2. Susceptibility testing revealed that the
      three blaNDM-5-positive isolates showed extensive resistance to antimicrobials.
      The blaNDM-5 gene was located on a ~46-kb IncX3 transferrable pNDM-MGR194-like
      plasmid in all three isolates, while mcr-1 was located on a ~260-kb IncHI2
      plasmid pXGE1mcr. Competition experiments revealed that acquisition of blaNDM-5
      or mcr-1-bearing plasmid can incur fitness cost of bacterial host, however,
      plasmid stability testing showed that both blaNDM-5 and mcr-1-carrying plasmid
      maintained stable in the hosts after ten passages without antimicrobial
      selection. Whole genome sequencing revealed that the mcr-1 gene coexisted with
      multiple resistance genes in pXGE1mcr and the backbone of this plasmid was
      similar to that of previously reported mcr-1-positive plasmid pHNSHP45-2.
      Moreover, pXGE1mcr could be conjugated into clinical NDM-5-positive E. coli
      isolates in vitro, thereby generating strains that approached pan-resistance.
      Active surveillance efforts are imperative to monitor the prevalence of blaNDM-5
      and mcr-1 in carbapenem-resistant Enterobacteriaceae from dairy farms throughout
      China.

PMID- 28757016
TI  - Characterization of Corynebacterium diphtheriae, C. confusum and C. amycolatum
      isolated from sows with genitourinary infection.
AB  - Porcine Corynebacterium infection is still poorly studied, even though the pig
      has been described as an asymptomatic carrier of Corynebacterium species,
      including the zoonotic species C. ulcerans, C. confusum and C. amycolatum. Here
      we present the identification, molecular and antimicrobial susceptibility
      characterization of coryneform bacteria isolated from sows with urinary tract
      infection. C. diphtheriae, C. confusum and C. amycolatum were isolated from sows
      with urinary infection and metritis. Corynebacterium species were identified by
      MALDI-TOF MS and confirmed by 16S rRNA and rpoB sequencing. All porcine C.
      diphtheriae strains were further characterized as non-toxigenic (tox-). SE-AFLP
      genotyping was also performed and enabled not only Corynebacterium species
      differentiation but also the assessment of C. amycolatum genetic heterogeneity.
      All studied porcine Corynebacterium strains presented alarming resistance
      profiles with high MIC values for macrolides/lincosamide, tetracyclines and
      quinolones, which can be related with high usage in both veterinary and human
      medicine. Isolation of zoonotic Corynebacterium species from commercial swine is
      important for assessing the potential zoonotic risk for farmers and further
      implication for both human and animal treatment.

PMID- 28757018
TI  - Glycan-specificity of four neuraminidase-sensitive animal rotavirus strains.
AB  - Group A rotaviruses (RVAs) are divided into neuraminidase (NA)-sensitive and NA
      insensitive strains depending upon their binding affinity to the VP8* domain in
      the terminal sialic acids (SAs) of cell surface carbohydrates. Although NA
      sensitive strains are known to use terminal SAs as an attachment factor, the
      exact nature of this attachment factor is largely unknown. Here we show that the
      specific linkage of SA-containing glycan to glycoprotein or glycolipid is an
      attachment factor used by NA-sensitive porcine G9P[7] PRG9121 and G9P[23] PRG942,
      bovine G6P[1] NCDV, and canine G3P[3] strains. Infectivity of porcine G9P[7] and
      G9P[23] strains was markedly blocked by alpha2,3-linkage and alpha2,6-linkage
      inhibitors, indicating that these strains bind to both alpha2,3- and alpha2,6
      linked SAs. However, the infectivity of bovine G6P[1] and canine G3P[3] strains
      was significantly reduced by alpha2,6-linkage inhibitor but not by alpha2,3
      linkage blockers, demonstrating a predilection of these strains for alpha2,6
      linked SAs. The infectivity of four NA-sensitive strains was equally reduced by
      inhibitors of lipid membrane and N-linked glycoprotein but not by an inhibitor of
      O-linked glycoprotein, indicating that these strains utilize both glycolipid and
      N-linked glycoprotein. Our study demonstrates that four NA-sensitive animal
      strains could have a strain-dependent binding preference toward alpha2,6-linked
      SAs (P[1] NCDV and P[3] CU-1 strains) or both alpha2,3- and alpha2,6-linked SAs
      (P[7] PRG9121 and P[23] PRG942 strains) to the glycolipid and N-linked
      glycoprotein.

PMID- 28757019
TI  - Genomic comparison of virulent and non-virulent serotype V ST1 Streptococcus
      agalactiae in fish.
AB  - Streptococcus agalactiae or Group B Streptococcus (GBS) is the major pathogen
      causing pneumonia and meningitis in human, mastitis in dairy cows, and
      streptococcal disease in tilapia. Previous studies have shown that fish GBS
      strains are correlated with human GBS strains in evolution and might have cross
      host infection ability. Although the invasive disease caused by ST1 GBS in non
      pregnant adults and cows is increasing worldwide, infection of fish by ST1 GBS
      has not been reported. The aim of this study was to determine whether ST1 GBS was
      virulent in fish and to investigate the genomic characteristics of ST1 GBS
      strains with different pathogenicity in tilapia. The human-derived serotype V ST1
      GBS strains NNA048 and NNA038 were used to intraperitoneally challenge Nile
      tilapia (Oreochromis niloticus) with doses of 1.0*109CFU/fish, 1.0*107CFU/fish,
      and 1.0*105CFU/fish, respectively. The cumulative mortality rates of NNA048
      infection at three different doses were 100.00%, 83.33%, and 40.00%. In contrast,
      there were no any sick or dead fish in NNA038 infection group. Histopathological
      results indicated that challenge of tilapia with NNA048 caused different degree
      of degeneration and necrosis in brain, liver, spleen, head kidney, and gut, and a
      large number of blue-stained Streptococcus granules were observed in the tissues.
      In contrast, there were no any lesions in the tissues of tilapia that were
      challenged with NNA038. Genome comparison showed that the major genome
      differences between NNA048 and NNA038 were attributed to the different phage
      sequences, and there was a 49.8kb length, intact phage sequence encoding 68
      proteins in NNA048 genome. SNV and Indels analysis between NNA038 and NNA048
      genomes indicated that there were a total of 96 SNVs, 5 deletions and 1 insert.
      Taken together, serotype V ST1 GBS was comprised of virulent and nonvirulent
      strains to tilapia, and gene rearrangement might be the main reason of causing
      different levels of virulence between strains.

PMID- 28757020
TI  - Experimental infection of Tilapia Lake Virus (TiLV) in Nile tilapia (Oreochromis
      niloticus) and red tilapia (Oreochromis spp.).
AB  - Since 2015, a novel orthomyxo-like virus, tilapia lake virus (TiLV) has been
      associated with outbreaks of disease and massive mortality of cultured Nile and
      red tilapia (Oreochromis niloticus and Oreochromis spp., respectively) in
      Thailand. In this study, TiLV was isolated from field samples and propagated in
      the permissive E-11 cell line, with cytopathic effect (CPE) development within 3
      5days post-inoculation. Electron micrographs of infected E-11 cells and fish
      tissues confirmed the rounded, enveloped virions of 60 to 80nm with
      characteristics very similar to those of Orthomyxoviridae. In vivo challenge
      studies showed that high mortality in Nile (86%) and red tilapia (66%) occurred
      within 4-12days post-infection. The virus was re-isolated from challenged fish
      tissues in the permissive cell line, and PCR analysis confirmed TiLV as a
      causative pathogen. The distinct histopathology of challenged fish included
      massive degeneration and inflammatory cell infiltration in the liver and brain as
      well as the presence of eosinophilic intracytoplasmic inclusions in hepatocytes
      and splenic cells. Our results fulfilled Koch's postulates and confirmed that
      TiLV is an etiologic agent of mass mortality of tilapia in Thailand. The
      emergence of this virus in many countries has helped increase awareness that it
      is a potential threat to tilapia aquacultured in Thailand, Asia, and worldwide.

PMID- 28757021
TI  - Prevalence of novel porcine circovirus 3 in Korean pig populations.
AB  - Porcine circovirus 3 (PCV3) is a novel porcine circovirus that was identified in
      pigs with porcine dermatitis and nephropathy syndrome, reproductive failure, and
      multi-systemic inflammation. However, the distribution and genetic
      characteristics of emerging PCV3 in Korea remains unclear. In this study, we
      determined the nationwide prevalence and genetic characteristics of PCV3 using
      pen-based oral fluid samples. The total prevalence of PCV3 in individual samples
      and at the farm level was 44.2% (159/360) and 72.6% (53/73), respectively. Korean
      PCV3 shared 99.2+/-0.2% (98.9-99.8%) and 98.6+/-0.5% (97.9-99.8%) nucleotide
      identity in the complete genome and ORF2, respectively, when compared to those of
      US strains. These data suggested that PCV3 is widely distributed throughout
      Korean pig populations.

PMID- 28757022
TI  - A review of methods used for studying the molecular epidemiology of Brachyspira
      hyodysenteriae.
AB  - Brachyspira (B.) spp. are intestinal spirochaetes isolated from pigs, other
      mammals, birds and humans. In pigs, seven Brachyspira spp. have been described,
      i.e. B. hyodysenteriae, B. pilosicoli, B. intermedia, B. murdochii, B. innocens,
      B. suanatina and B. hampsonii. Brachyspira hyodysenteriae is especially relevant
      in pigs as it causes swine dysentery and hence considerable economic losses to
      the pig industry. Furthermore, reduced susceptibility of B. hyodysenteriae to
      antimicrobials is of increasing concern. The epidemiology of B. hyodysenteriae
      infections is only partially understood, but different methods for detection,
      identification and typing have supported recent improvements in knowledge and
      understanding. In the last years, molecular methods have been increasingly used.
      Molecular epidemiology links molecular biology with epidemiology, offering unique
      opportunities to advance the study of diseases. This review is based on papers
      published in the field of epidemiology and molecular epidemiology of B.
      hyodysenteriae in pigs. Electronic databases were screened for potentially
      relevant papers using title and abstract and finally, Barcellos et al. papers
      were systemically selected and assessed. The review summarises briefly the
      current knowledge on B. hyodysenteriae epidemiology and elaborates on molecular
      typing techniques available. Results of the studies are compared and gaps in the
      knowledge are addressed. Finally, potential areas for future research are
      proposed.

PMID- 28757023
TI  - High reduced/oxidized glutathione ratio in infectious spleen and kidney necrosis
      virus-infected cells contributes to degradation of VP08R multimers.
AB  - Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the
      genus Megalocytivirus, family Iridoviridae. The ISKNV-infected cells in fish
      tissues are attached by lymphatic endothelial cells (LECs), which is a unique
      pathological phenomenon of ISKNV infection. The viral proteins VP23R and VP08R
      and the host protein nidogen-1 constitute the virus-mock basement membrane (VMBM)
      on the membrane of infected cells to provide attaching sites for LECs. VP08R can
      form cross-linked multimers via intermolecular disulfide bonds to make VMBM a
      compact and strong structure. A question is that when the virions mature, how do
      they penetrate VMBMs to be released from the cells? In this study, the redox
      state in ISKNV-infected cells was investigated. We demonstrated that the ratio of
      reduced/oxidized glutathione (GSH/GSSG) was significantly elevated in ISKNV
      infected cells, suggesting the increasing of reducing power. Remarkable changes
      were also observed in activities of many GSH metabolic enzymes and in the ratio
      of NADPH/NADP. We further exhibited that the high ratio of GSH/GSSG could lead to
      degradation of the VP08R multimer in vitro. These may suggest that the high
      GSH/GSSG ratio in infected cells could act on the VP08R multimer to facilitate
      the disassembly of VMBMs after virus maturation.

PMID- 28757024
TI  - 16S rRNA genes Illumina sequencing revealed differential cecal microbiome in
      specific pathogen free chickens infected with different subgroup of avian
      leukosis viruses.
AB  - Intestinal flora play important roles in the pathogenisis of many pathogens. This
      study examined the cecal microbiome of chickens infected with avian leukosis
      virus (ALV) using 16S rRNA genes Illumina sequencing. One-day-old specific
      pathogen free chicks were inoculated in the abdomen with subgroup J or K of ALV.
      At 21-day-old, chickens positive for ALV viremia were selected and their cecal
      contents were extracted and examined for the composition of gut microflora by
      illumina sequencing of the V3+V4 region of the 16S rRNA genes. The results showed
      that there is a clear association with loss of important bacterial populations in
      concert with an enrichment of potentially pathogenic populations and ALV
      infections, despite of the virus subgroups. In addition, ALV-K infected chickens
      revealed a preference for opportunistic pathogens in Firmicutes such as
      Staphylococcus and Weissella and some genus from Bacillales. Whereas, ALV-J
      infected chickens were characterized by a larger number of notable pathogens like
      Escherichia-Shigella from Proteobacteria, and other condition pathogens including
      Enterococcus and members of Erysipelotrichaceae from Firmicutes, and members of
      Helicobacteraceae from Bacteroidetes. Collectively, our results suggest that
      relative abundance data from the cecal microbiome differentiates healthy chickens
      from those infected with ALVs. Most importantly, there was a significant
      difference in the gut microbiome of chickens infected with ALV-K compared to
      those with ALV-J infected ones. This strongly suggests that ALV infection may be
      associated with the microbiome and there may be multiple underlying mechanisms by
      which the microbiome is involved in the pathogenisis of different subgroup of ALV
      infections.

PMID- 28757025
TI  - Epidemiology and molecular detection of equine herpesviruses in western Algeria
      in 2011.
AB  - An episode of acute equine respiratory infection was reported in western Algeria
      (Tiaret province) between February and March 2011, affecting a large population
      of horses. Nasal swabs (n=100) were taken from horses aged between 1 and 27
      years, presenting with cough and mucopurulent nasal discharge. The prevalence of
      equine respiratory virus infections was examined using quantitative polymerase
      chain reaction (qPCR). One, or more, of four equine respiratory viruses were
      detected in the nasal swabs of 90 of 100 horses (90%) and the detection rate of
      equine herpesvirus type 1 (EHV-1), equine herpesvirus type 4 (EHV-4), equine
      herpesvirus type 2 (EHV-2) and equine herpesvirus type 5 (EHV-5) were 2%, 14%,
      90% and 75%, respectively. Equine influenza virus and equine arteritis virus were
      not detected in any samples. Among the 90 infected horses, 70 were co-infected
      with EHV-2 and EHV-5 and 14 others were co-infected with EHV-4, EHV-2 and EHV-5.
      The present study shows a positivity rate of 97.3% for EHV-5 in young horses aged
      <3years; a finding which decreased with age. Viral load of EHV-5 was
      significantly higher in <3years whereas no effect of age was observed with EHV-2.
      The study shows that equine herpesviruses 1, 2, 4 and 5 are endemic in horse
      populations from Algeria as detected for the first time by qPCR.

PMID- 28757026
TI  - Marek's disease virus type 1 encoded analog of miR-155 promotes proliferation of
      chicken embryo fibroblast and DF-1 cells by targeting hnRNPAB.
AB  - Marek's disease virus type 1 (MDV-1) is a representative oncogenic Alpha
      herpesvirus that causes an immunosuppressive and neoplastic lymphoproliferative
      avian disease, namely Marek's disease (MD). The rapid-onset T-cell lymphoma in
      chickens induced by MDV-1 has been historically regarded as an ideal natural
      model for herpesvirus-related cancer research. As a viral analog of cellular miR
      155, the MDV-1-encoded miR-M4-5p has been shown to be crucial for the virally
      induced MD tumorigenesis. Our previous studies demonstrated that miR-M4-5p
      induces an over-expression of oncogene c-Myc by targeting LTBP1 and suppressing
      the TGF-beta signaling pathway during MDV-1 infection. We have now further
      identified the chicken heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) as a
      new cellular biological target for miR-M4-5p. Suppression of hnRNPAB expression
      mediated by miR-M4-5p promotes the proliferation, but not the apoptosis, of both
      primary chicken embryo fibroblasts (CEFs) and transformed chicken fibroblast DF-1
      cell line. HnRNPAB is a member of the hnRNP family of proteins that play
      important roles in normal biological processes as well as cancer development. Our
      data suggests that the recognition and down-regulation of hnRNPAB by miR-M4-5p
      may be one of the important strategies for MDV-1 to trigger the development of MD
      lymphomas.

PMID- 28757027
TI  - Salmonella serovar-specific interaction with jejunal epithelial cells.
AB  - Gut is often a receptacle for many different pathogens in feed and/or the
      environment, such as Salmonella spp. The current knowledge about pathogenicity of
      Salmonella is restricted to few serotypes, whereas other important ones like S.
      Coeln, S. Thompson, S. Veneziana, have not been investigated yet in human and
      animal models. Therefore, the aim of our work was to verify the ability of
      widespread environmental Salmonella strains to penetrate and modulate innate
      immunity in pig intestinal IPEC-J2 cells. Our results outline the different
      ability of Salmonella strains to modulate innate immunity; the expression of the
      IFN-beta gene was increased by S. Typhimurium, S. Ablogame and S. Diarizonae 2,
      that also caused an inflammatory response in terms of Interleukin (IL)-1beta
      and/or IL-8 gene espression. In particular, IL-8 gene expression and protein
      release were significantly modulated by 5 Salmonella strains out of 7.
      Interestingly, S. Typhimurium, S. Coeln and S. Thompson strains, characterized by
      a peculiar ability to penetrate into IPEC-J2 cells, up-regulated both IL-8 and
      TNF-alpha gene expression. Accordingly, blocking IL-8 was shown to decrease the
      penetration of S. Typhimurium. On the contrary, S. Diarizonae strain 1, showing
      lesser invasion of IPEC-J2 cells, down-regulated the p38-MAPK pathway, and it did
      not induce an inflammatory response. Our results confirm that IPEC-J2 cells are a
      useful model to evaluate host-gut pathogen interaction and indicate IL-8 and TNF
      alpha as possible predictive markers of invasiveness of Salmonella strains in
      enterocytes.

PMID- 28757028
TI  - Campylobacter hepaticus, the cause of spotty liver disease in chickens, is
      present throughout the small intestine and caeca of infected birds.
AB  - Spotty liver disease (SLD) causes significant egg production losses and mortality
      in chickens and is therefore a disease of concern for some sectors of the poultry
      industry. Although the first reports of the disease came from the United States
      in the 1950s it is only recently that the organism that causes the disease was
      identified, isolated, and characterised as a new bacterial species, Campylobacter
      hepaticus. The first isolations of C. hepaticus were from the livers and bile of
      SLD affected birds. Isolates could only be recovered from samples that had a
      monoculture of C. hepaticus in the tissues, as a selective culturing method has
      not yet been developed. In non-selective growth conditions the slow growing C.
      hepaticus is quickly outgrown by many other members of the chicken microbiota.
      Therefore, it is currently not possible to use a culturing approach to evaluate
      C. hepaticus carriage in tissues, such as the gastrointestinal tract (GIT), that
      also carry complex microbial populations. As it is suspected that birds become
      infected via the faecal-oral route it is important that pathogen carriage in the
      GIT is investigated. In the present study, a specific and sensitive quantitative
      real-time PCR assay, based on the glycerol kinase gene of C. hepaticus, was
      developed. The assay facilitated the detection and quantification of C. hepaticus
      in tissue samples from clinical cases of SLD. It was shown that in infected birds
      C. hepaticus colonises the small intestine, increasing in abundance from duodenum
      to ileum, and is at highest levels within the ceaca. C. hepaticus was also
      readily detected in cloacal swabs, indicating that thecl-oral infection.

PMID- 28757029
TI  - Diversity of Streptococcus equi subsp. zooepidemicus strains isolated from the
      Spanish sheep and goat population and the identification, function and prevalence
      of a novel arbutin utilisation system.
AB  - The zoonotic bacterium Streptococcus equi subsp. zooepidemicus (S. zooepidemicus)
      is a diverse, opportunistic pathogen that can cause mastitis in dairy sheep and
      goats. We used multilocus sequence typing (MLST) to define the genetic diversity
      of 60 isolates of S. zooepidemicus, which were recovered from sheep and goats in
      Spain between 2003 and 2010. We identify a novel clonal complex based on sequence
      type (ST), ST-236, which accounted for 39 of the 60 isolates. A representative ST
      236 strain, S. zooepidemicus strain C7 (SzC7), was sequenced and interrogated for
      the presence of novel nutritional uptake or utilisation systems, the acquisition
      of which have previously been shown to be important for environmental adaptation
      in other streptococcal pathogens. A novel phosphoenolpyruvate sugar
      phosphotransferase system (PTS), which enabled the utilisation of arbutin, was
      identified. Functionality of the PTS was confirmed following deletion of the PTS
      from SzC7. Arbutin is found in multiple animal foodstuffs and we propose that the
      ability to utilise arbutin may have conferred a selective advantage to strains
      infecting animals, the diet of which contains this sugar.

PMID- 28757031
TI  - Genetic characteristics, pathogenicity, and immunogenicity associated with cell
      adaptation of a virulent genotype 2b porcine epidemic diarrhea virus.
AB  - Porcine epidemic diarrhea virus (PEDV) has emerged or re-emerged worldwide,
      posing a significant financial threat to major pig-producing countries. In the
      present study, a virulent Korean pandemic PEDV strain, KNU-141112, was serially
      propagated in Vero cells for up to 100 passages. Through cell culture adaptation,
      we obtained four distinct deletion (DEL) mutants by plaque purification followed
      by nucleotide sequencing of the spike (S)/ORF3 gene-coding region, which were
      designated KNU-141112-S DEL2, -S DEL5, -S DEL2/ORF3, and -S DEL5/ORF3. Further
      whole genome sequencing identified 12 or 14 amino acid changes in the cell
      adapted DEL strains. Animal inoculation studies revealed that the virulence of
      both S DEL2/ORF3 and S DEL5/ORF3 viruses with a large 46-nt deletion in the
      intergenic portion of S and ORF3 was remarkably diminished, indicating viral
      attenuation in the natural host. Furthermore, these cell-adapted strains elicited
      potent neutralizing antibody responses in immunized pigs. Taken together, our
      data indicate that the cell-attenuated S DEL2/ORF3 and S DEL5/ORF3 strains are
      promising candidates for the development of a safe and effective live PEDV
      vaccine.

PMID- 28757030
TI  - Identification and genetic characterization of equine hepaciviruses in Italy.
AB  - Viruses similar to human hepatitis C virus, hepaciviruses, have been identified
      in various animal species. Equine hepacivirus (EqHV) is the closest relative of
      human hepaciviruses. Although detected worldwide, information on EqHV
      epidemiology, genetic diversity and pathogenicity is still limited. In this study
      we investigated the prevalence and genetic diversity of EqHV in Italian equids.
      The RNA of EqHV was detected in 91/1932 sera (4.7%) whilst it was not detectable
      in 134 donkey sera screened by a TaqMan-based quantitative assay. Upon sequencing
      and phylogenetic analysis of genomic portions located in the NS5B, 5'UTR and NS3
      genes, the Italian EqHV strains segregated into two distinct clades that are also
      co-circulating globally, without apparent geographic restrictions.

PMID- 28757032
TI  - Incidence of postoperative implant-related bacterial endocarditis in dogs that
      underwent trans-catheter embolization of a patent ductus arteriosus without intra
      and post-procedural prophylactic antibiotics.
AB  - Intra- and post-procedural prophylactic antibiotics are routinely administered by
      veterinary cardiologists to dogs that undergo trans-catheter embolization of a
      patent ductus arteriosus for prevention of implant-related infective
      endocarditis. The hypothesis of our study was that primary antibiotic prophylaxis
      is not necessary to prevent bacterial endocarditis. In this retrospective case
      series 54 client-owned dogs that underwent trans-catheter occlusion of a patent
      ductus arteriosus in a single tertiary veterinary referral center between 2004
      and 2016 were evaluated. Follow-up information was gained by telephone interviews
      with the owners or the referring veterinarians, or from the digital archives of
      the authors' clinic. Inclusion criteria were that at least one metal implant (a
      coil or an Amplatz duct occluder) had to be delivered in the ductal ampulla, no
      local or systemic antibiotics were given on the day of the intervention or the
      week thereafter, at least 3 months of postoperative follow-up information was
      available, and the author was performing the procedure either as the primary or
      as the supervising cardiology specialist. None of the 54 dogs developed infective
      endocarditis in the postoperative 3 months. A study describing a similar
      population reports 2 of the included 47 dogs having developed infective
      endocarditis in the postoperative period despite the administration of intra- and
      post-procedural prophylactic antibiotics. We conclude that intra- and post
      procedural antibiotic prophylaxis is not justified in dogs that undergo trans
      catheter closure of a patent ductus arteriosus. Proper surgical technique and the
      use of new sterile catheters and implants are sufficient to prevent infective
      endocarditis in these dogs.

PMID- 28757033
TI  - Commensal coagulase-negative Staphylococcus from the udder of healthy cows
      inhibits biofilm formation of mastitis-related pathogens.
AB  - Bovine mastitis, considered the most important cause of economic losses in the
      dairy industry, is a major concern in veterinary medicine. Staphylococcus aureus
      and coagulase-negative staphylococci (CNS) are the main pathogens associated with
      intramammary infections, and bacterial biofilms are suspected to be responsible
      for the persistence of this disease. CNS from the udder are not necessarily
      associated with intramammary infections. In fact, some commensal CNS have been
      shown to have biological activities. This issue led us to screen exoproducts from
      commensal Staphylococcus chromogenes for anti-biofilm activity against different
      mastitis pathogens. The cell-free supernatant from S. chromogenes LN1 (LN1-CFS)
      was confirmed to display a non-biocidal inhibition of pathogenic biofilms. The
      supernatant was subjected to various treatments to estimate the nature of the
      biofilm-inhibiting compounds. The results showed that the bioactive compound
      >5KDa in mass is sensitive to thermal treatment and proteinase K digestion,
      suggesting its protein properties. LN1-CFS was able to significantly inhibit S.
      aureus and CNS biofilm formation in a dose-independent manner and without
      affecting the viability of bovine cells. These findings reveal a new activity of
      the udder microflora of healthy animals. Studies are underway to purify and
      identify the anti-biofilm biocompound and to evaluate its biological activity in
      vivo.

PMID- 28757034
TI  - Microbial community sequencing analysis of the calf eye microbiota and
      relationship to infectious bovine keratoconjunctivitis.
AB  - Infectious bovine keratoconjunctivitis (IBK) is an important production limiting
      disease in cattle. Moraxella bovis has historically been considered the primary
      causal agent; however, vaccines have not been consistently shown as effective in
      controlling disease incidence. The purpose of this study was to examine the
      bacterial community of calf eyes prior to disease onset using high-throughput
      sequencing of 16S ribosomal RNA and determine if it was associated with IBK
      occurrence. The study was designed as a case-control nested within a randomized
      controlled trial (RCT). Eye swabs were collected from all spring-born calves
      without clinical signs of IBK (t0 swabs) on a research farm with a previous
      history of IBK disease outbreaks. At follow-up or weaning, calves were diagnosed
      as IBK positive or negative. The lag time between enrollment swabs (t0) and IBK
      diagnosis ranged from approximately one to three months. Cases were randomly
      selected from IBK positive calves and controls were selected from IBK negative
      calves (i.e. calves that did not exhibit clinical signs of IBK throughout the
      course of the RCT). Analysis of the fold-change differences between cases and
      controls did not reveal large-scale distinctions in bacterial composition.
      However, principal component analysis suggested bacterial composition differences
      between calf management groups, which were based on dam parity. Moraxella was
      found to be among the top ten most abundant genera in our population; however,
      the difference in abundance was not significant between the cases and controls.
      No large-scale differences in the bacterial communities of calves that did or did
      not develop IBK were observed in our population. Nevertheless, it remains unclear
      whether the "natural" bacterial population of the calf might ultimately impact
      disease status. Further study is warranted to examine bacterial taxa that were
      observed to be significantly more abundant in the cases or controls as potential
      vaccines/therapeutic targets.

PMID- 28757035
TI  - Characterization of Akabane virus from domestic bamboo rat, Southern China.
AB  - To identify the causative agents in 3 large-scale outbreaks of encephalitis and
      death among farmed bamboo rats (Rhizomys pruinosus). The routine bacterial
      culture and identification were performed. There were no significant pathogenic
      bacteria isolated from the brain, heart, liver, spleen, lung, or kidney of
      diseased bamboo rats. Using PCR-based methods, we excluded the following as
      causative agent: pox virus, herpesvirus, adenovirus, lymphocytic choriomeningitis
      virus, rabies virus, and sendai virus. Furthermore, the homogenate from the
      diseased bamboo rats was subjected to viral metagenomic analysis which revealed
      48506 filtered viral reads annotated to Akabane virus (AKAV) with >75% nucleotide
      identity, suggesting the presence of AKAVs in bamboo rats. Five novel AKAV
      isolates were successfully isolated and characterized. Furthermore the newly
      isolated AKAV isolate was used to demonstrate that it can reproduce the severe
      encephalitic and pneumonic disease in bamboo rats and mice. The findings add to
      the better understanding of AKAV epidemiology and to the prevention and control
      of Akabane diseases in China.

PMID- 28757036
TI  - The phenotypic and molecular resistance induced by a single-exposure to sub
      mutant prevention concentration of marbofloxacin in Salmonella Typhimurium
      isolates from swine.
AB  - In the present study, the molecular mechanisms of antibiotic resistance in
      Salmonella Typhimurium clinical isolates from pigs were investigated using a
      single-step mutation model of exposure to sub-mutant prevention concentrations
      (MPCs) of marbofloxacin. The minimum inhibitory concentrations (MICs) of seven
      antibacterial drugs were evaluated against 30 S. Typhimurium clinical isolates
      from different pigs. MPCs of marbofloxacin were also determined. The mechanism of
      marbofloxacin-resistance was investigated by sequencing analysis of target gene
      mutations and quantifying the overexpression of efflux pumps and their regulators
      by quantitative RT-PCR. Marbofloxacin showed the highest potency against all
      isolates (23.3%), including multi-drug resistant isolates. The MPC50 (0.5MUg/mL)
      and MPC90 (2MUg/mL) of marbofloxacin were determined, as were MPC/MIC ratios of
      2.5 to 8. A gyrA mutation (Ser83Phe or Asp87His) was detected in isolates with an
      MIC>0.06MUg/mL and all single-step mutants. Moreover, expression of acrAB-tolC
      and marA/soxS/ramA increased following a single-step mutation, but only ramA
      expression showed a positive correlation with the resistance phenotype of
      clinical isolates and single-step mutants (p<0.05). Furthermore, the acrR
      mutation was detected in two clinical isolates and 50% of single-step mutants,
      regardless of whether the gyrA mutation was present. This is the first report of
      acrR mutations in S. Typhimurium isolates from pigs in Korea. Our findings
      suggest that a single-exposure to sub-MPCs of marbofloxacin was sufficient to
      reduce the susceptibility of Salmonella isolates. Therefore, optimized dosing
      based on application with the MPC concept is required to reduce the chances of
      marbofloxacin resistance.

PMID- 28757037
TI  - Multiple amino acid substitutions involved in the virulence enhancement of an
      H3N2 avian influenza A virus isolated from wild waterfowl in mice.
AB  - Frequent emergence of low pathogenic avian influenza H3N2 viruses in the wild
      birds has caused concern for human health. Here, we generated mouse-adapted
      strains of a wild waterfowl-origin low pathogenic avian influenza H3N2 virus to
      identify adaptive mutations that confer enhanced virulence in mammals. The mouse
      lethal doses (MLD50) of the adapted strains were reduced >562-fold compared to
      the parental virus. Mouse-adapted strains displayed enhanced replication in vitro
      and in vivo, and acquired the ability to replicate in extrapulmonary tissues.
      These observations suggest that enhanced growth characteristics and modified cell
      tropism may increase the virulence of H3N2 AIVs in mice. Genomic analysis
      revealed mutations in the PB2 (E192K and D701N), PB1 (F269S, I475V, and L598P),
      HA (V242E), NA (G170R), and M1 (M192V) proteins. Our results suggest that these
      amino acid substitutions collaboratively enhance the ability of H3N2 avian
      influenza A virus to replicate and cause severe disease in mammals.

PMID- 28757038
TI  - Livestock-associated methicillin-resistant Staphylococcus aureus is widespread in
      farmed mink (Neovison vison).
AB  - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clonal
      complex (CC) 398 is widespread in the Danish pig production with around 90% of
      herds being positive. Since 2009, cases of CC398 LA-MRSA infections in Danish
      mink farmers have been observed. The objective of the study was to examine the
      presence of LA-MRSA in farmed mink. The investigation comprised three different
      sample types 1) clinical samples from carcasses submitted to the laboratory for
      diagnostic examination, 2) paws and pharyngeal swabs from healthy animals
      collected at pelting, and 3) feed samples from mink feed producers. In clinical
      samples, LA-MRSA was found in 34% of submissions and was most prevalent in
      samples from paws (33%) and pharynx (17%), followed by nasal and intestinal
      samples (each 13%), whereas it was never detected in perineal samples. LA-MRSA
      was found in healthy animals on 40% of the investigated farms, including paw
      samples (29%) and pharyngeal samples (16%). Twenty out of the 108 feed samples
      from feed producers were positive for LA-MRSA. The dominant spa-types were t034
      and t011 associated to CC398, corresponding to the dominant spa-types detected in
      the Danish pig production, from which slaughter offal is used for mink feed. The
      spa-types, the high prevalence of LA-MRSA on paws and in pharynx, and its
      detection in feed samples, suggest feed as a possible source of LA-MRSA in mink.

PMID- 28757039
TI  - Genomic characterisation of Felis catus papillomavirus type 5 with proposed
      classification within a new papillomavirus genus.
AB  - Four Felis catus papillomavirus (FcaPV) types have been fully sequenced from
      domestic cats. Of these, FcaPV-2 and -3 are thought to cause feline viral plaques
      and Bowenoid in situ carcinomas. Two short sequences of DNA from a previously
      unreported PV type were amplified from a feline viral plaque using consensus PCR
      primers. DNA was then extracted from a swab of the lesion and two sets of
      'outward facing' primers were designed using the short sequences to amplify the
      entire 7600bp genome of the novel PV. The PV was designated FcaPV-5 and contained
      putative coding regions that were predicted to produce five early proteins and
      two late ones. The ORF L1 showed over 65% similarity to that of FcaPV-3 and -4.
      Assignment to a genus was difficult as the PV was over 60% similar to PV types
      from 4 different genera. However, due to the ORF L1 similarity of FcaPV-3, -4,
      and -5, the shared host species of all three PVs, and the similar lesions
      associated with FcaPV-3 and -5, it is proposed all three PVs are classified
      within a new genus. FcaPV-5 is the third PV type to be associated with feline
      viral plaques. The plaque that contained FcaPV-5 showed unusual histological
      features including hyperplasia and PV-induced cell changes in sebaceous glands
      and deep within hair follicles. While additional study of further lesions of this
      type is required, it is possible that FcaPV-5 may be able to infect a broader
      range of cells than other PV types.

PMID- 28757040
TI  - Porcine parvovirus infection activates inflammatory cytokine production through
      Toll-like receptor 9 and NF-kappaB signaling pathways in porcine kidney cells.
AB  - Porcine parvovirus virus (PPV) is an animal virus that has caused high economic
      losses for the swine industry worldwide. Previous studies demonstrated that PPV
      infection induced significant production of interleukin 6 (IL-6) in vitro and in
      vivo. However, the inflammatory cytokines and specific signaling pathways induced
      during PPV infection remain largely unknown. In the present study, we analyzed
      the expression levels of IL-6 in PPV-infected porcine kidney 15 (PK-15) and the
      results showed that PPV infection induced the increase of IL-6 mRNA expression in
      a dose-dependent manner. We also detected the expression of toll-like receptor 9
      (TLR9) signaling proteins in the mRNA expressing level, when compared with the
      control group, the TLR9 expression in mRNA level increased at 24h in PK-15 cells
      after PPV infection and reached the peak level at 48h. In addition, the
      transcript profile of nuclear factor kappa B (NF-kappaB) signal pathway relating
      genes (MyD88, IRAK1, TRAF6, TAK1alpha, IkappaBkappaB and NF-kappaB) expression
      levels increased at different times. Furthermore, to verify the IL-6 expression
      was specific with the TLR9 expression and then by activating the NF-kappaB signal
      pathway, TLR9 and NF-kappaB specific inhibitors were applied during PPV
      infection, separately, the result indicated that the expression of IL-6 was
      decreased after inhibitor treatment. Taken together, PPV infection significantly
      induced IL-6 expression and this induction depended on NF-kappaB activation and
      TLR9 signaling pathways in PK-15 cell.

PMID- 28757041
TI  - Mutations in the quinolone resistance determining region conferring resistance to
      fluoroquinolones in Mycoplasma agalactiae.
AB  - M. agalactiae is the main causative agent of contagious agalactia, against which
      antimicrobial treatment is the main applied control measure. Quinolones are an
      effective group of antimicrobials inhibiting the growth of M. agalactiae, but in
      the last years, various reports have demonstrated an increase of resistance in
      field isolates due to its massive use. Nevertheless, the molecular mechanisms
      involved in the acquisition of fluoroquinolones resistance in M. agalactiae have
      not been elucidated yet. Therefore, the aim of this work was to analyze the
      presence of DNA variations that could be related to changes in fluoroquinolone
      susceptibility. For this purpose, three M. agalactiae strains were selected to
      obtain in vitro resistant mutants against enrofloxacin, marbofloxacin and
      moxifloxacin and afterwards, partial sequences of their gyrA, gyrB, parC and parE
      genes were analyzed. In addition, a set of field isolates with different MIC
      values were also studied. Changes related to variations in fluoroquinolones
      susceptibility were found in gyrB, parC and parE. Specifically, gyrB genes were
      affected at the predicted amino acid position 424, four amino acid changes were
      detected in parC (positions 78, 79, 80 and 84) and two substitutions were
      reported in parE (amino acid positions 429 and 459). Mutations at predicted
      positions 424 of gyrB and 429 of parE are novel DNA changes which had not been
      previously described and, on the whole, parC was the first gene showing
      alterations when changes in susceptibility to fluoroquinolones occurred. Thus,
      this gene is the most suitable target for a rapid study of fluoroquinolone
      resistance in field isolates of M. agalactiae.

PMID- 28757042
TI  - Occurrence and characterization of stx and/or eae-positive Escherichia coli
      isolated from wildlife, including a typical EPEC strain from a wild boar.
AB  - Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC) strains
      are food-borne pathogens associated with acute diarrhea. Haemolytic-uremic
      syndrome (HUS) is often a complication of STEC infection. In order to examine the
      occurrence, serotypes, virulence and antimicrobial-resistance profiles of STEC
      and EPEC in wildlife, 326 faecal E. coli strains from 304 clinically healthy
      animals were analyzed. For this approach stx1, stx2 and eae genes, as well as
      accessory virulence determinants (ehx, hlyA, saa, tia, bfp, subAB) were PCR
      screened and sequenced. Serotyping was performed employing all available O (O1
      O185) and H (H1-H56) antisera. Genetic diversity was analyzed by XbaI-PFGE and
      phylotyping. Thirteen STEC (4.3%) and 10 EPEC (3.3%) were identified among 12
      deer, 3 mouflon, 6 wild boars and 2 birds. Nine STEC showed seropathotypes B
      (O145:[H28]) and C (O22:H8, O128:[H2]) associated with HUS, and D (O110:H28,
      O146:H21, O146:[H28], ONT:H8) associated with human diarrhea. Although most
      isolates harbored stx2b and stx1c variants, stx2a and stx1a (related with severe
      disease) were also detected. Additionally, the eae gene was present in one stx2a
      positive O145:[H28] STEC from a deer and 11 STEC harbored subAB genes (mainly the
      subAB2 variant). EPEC isolates showed 7 different intimin variants (beta1, beta2,
      gamma1, epsilon1, zeta1, iota1-A, kappa). Interestingly, the O49:[H10] eae-kappa
      EPEC isolated from a wild boar was bfpA-positive showing a combination of
      serotype/virulence profile previously detected among human clinical tEPEC. Based
      on present results, wild ruminants, wild boars and to a lesser extent birds would
      be carriers of potentially pathogenic STEC and EPEC strains.

PMID- 28757043
TI  - A large-scale serological survey of Akabane virus infection in cattle, yak, sheep
      and goats in China.
AB  - Akabane virus (AKAV) is a member of the Simbu serogroup, classified in the genus
      Orthobunyavirus, family Bunyaviridae. AKAV infection can cause abortion,
      stillbirth, and congenital arthrogryposis and hydranencephaly in cattle and
      sheep. The distribution and prevalence of AKAV infection in China is still
      unknown. A total of 2731 sera collected from 2006 to 2015 in 24 provinces of
      China from cattle, sheep, goats and yak were examined by serum neutralisation
      test. The overall seroprevalence rates for AKAV antibodies were 21.3% in cattle
      (471/2215) and 12.0% (17/142) in sheep or goats, and 0% in yak (0/374). The
      results indicated widespread AKAV infection in China among cattle and sheep but
      yak appear to have a low risk of infection. Using a selection of 50 AKAV-positive
      and 25 AKAV-negative cattle sera, neutralisation tests were also conducted to
      detect antibodies to several other Simbu serogroup bunyaviruses and closely
      related Leanyer virus. Although inconclusive, the data suggest that both Aino
      virus and Peaton virus, which have been reported previously in Japan and Korea,
      may also be present in cattle in China.

PMID- 28757044
TI  - Fungal dermatitis, glossitis and disseminated visceral mycosis caused by
      different Metarhizium granulomatis genotypes in veiled chameleons (Chamaeleo
      calyptratus) and first isolation in healthy lizards.
AB  - Metarhizium (M.) granulomatis (formerly Chamaeleomyces granulomatis) invariably
      causes fatal fungal glossitis and systemic mycosis in veiled chameleons
      (Chamaeleo calyptratus). Isolation of M. granulomatis in other lizards thus far
      has not been described. The aim of this study therefore was to obtain information
      on the presence of M. granulomatis in reptiles kept as pets, and to examine
      whether there was an association between specific genotypes and
      clinical/pathological outcomes. Besides 18S ribosomal (r) DNA (SSU) and internal
      transcribed spacer1-5.8S (ITS1-5.8S) rDNA, a fragment of the large subunit of the
      28S rDNA (LSU), including the domains 1 (D1) and D2, were sequenced for
      identification of the fungus and phylogenetic analysis. Metarhizium granulomatis
      was isolated from 23 veiled chameleons, two panther chameleons (Furcifer
      pardalis) and one central bearded dragon (Pogona vitticeps). Only the veiled
      chameleons revealed corresponding pathological findings in the form of glossal
      hemorrhage, granulomatous glossitis, pharyngitis, dermatitis and/or visceral
      mycosis. The infection site correlated to survival times of infected veiled
      chameleons. Combined long-term treatment with terbinafine and nystatin based on
      susceptibility testing may be helpful for prevention of disease and visceral
      spreading of the fungus, but elimination of the fungal pathogen or successful
      treatment of diseased veiled chameleons have not been achieved yet. Sequencing of
      the ribosomal genes yielded five different genotypes, with genotype A being
      strongly correlated with dermatitis, and remaining genotypes with pharyngitis and
      glossitis. However, disseminated visceral mycosis developed irrespective of the
      genotypes.

PMID- 28757045
TI  - Efficacy of potential phage cocktails against Vibrio harveyi and closely related
      Vibrio species isolated from shrimp aquaculture environment in the south east
      coast of India.
AB  - A diverse set of novel phages infecting the marine pathogenic Vibrio harveyi was
      isolated from shrimp aquaculture environments in the south east coast of India.
      Based on initial screening, three phages with a broad host range revealed that
      the growth inhibition of phage is relatively specific to V. harveyi. They were
      also able to infect V. alginolyticus and V. parahemolyticus that belonged to the
      Harveyi clade species from shrimp pond and sea coast environment samples.
      However, the impact of these phages on their host bacterium are well understood;
      a one-step growth curve experiment and transmission electron microscope (TEM)
      revealed three phages grouped under the Myoviridae (VHM1 and VHM2); Siphoviridae
      (VHS1) family. These phages were further molecular characterized with respect to
      phage genomic DNA isolates. The randomly amplified polymorphic DNA (RAPD),
      restriction fragment length polymorphism (RFLP) digestion with HindIII, and major
      structural proteins were distinguished by sodium-dodecyl-sulfate polyacrylamide
      gel electrophoresis (SDS-PAGE) clearly indicated that all the phage isolates were
      different, even when they came from the same source, giving an insight into the
      diversity of phages. Evaluation of microcosm studies of Penaeus monodon larvae
      infected with V. harveyi (105 CFU mL-1) showed that larvae survival after 96 h in
      the presence of phage treatment at 109 PFU mL-1 was enhanced when compared with
      the control. The resolution in over survival highly recommended that this study
      provides the phage-based therapy which could be an innovative and eco-friendly
      solution against Vibrio disease in shrimp aquaculture and in the natural
      environment.

PMID- 28757046
TI  - Rapid acquisition adaptive amino acid substitutions involved in the virulence
      enhancement of an H1N2 avian influenza virus in mice.
AB  - Although H1N2 avian influenza virus (AIV) only infect birds, documented cases of
      swine infection with H1N2 influenza viruses suggest this subtype AIV may pose a
      potential threat to mammals. Here, we generated mouse-adapted variants of a H1N2
      AIV to identify adaptive changes that increased virulence in mammals. MLD50 of
      the variants were reduced >1000-fold compared to the parental virus. Variants
      displayed enhanced replication in vitro and in vivo, and replicate in
      extrapulmonary organs. These data show that enhanced replication capacity and
      expanded tissue tropism may increase the virulence of H1N2 AIV in mice. Sequence
      analysis revealed multiple amino acid substitutions in the PB2 (L134H, I647L, and
      D701N), HA (G228S), and M1 (D231N) proteins. These results indicate that H1N2 AIV
      can rapidly acquire adaptive amino acid substitutions in mammalian hosts, and
      these amino acid substitutions collaboratively enhance the ability of H1N2 AIV to
      replicate and cause severe disease in mammals.

PMID- 28757047
TI  - Need for randomized clinical trials testing targeted therapies in malignant
      pleural mesothelioma.

PMID- 28757048
TI  - A long-term multicenter study: Entecavir versus Tenofovir in treatment of
      nucleos(t)ide analogue-naive chronic hepatitis B patients.
AB  - BACKGROUND: Entecavir (ETV) and tenofovir disoproxil fumarat (TDF) are the two
      first-line therapies recommended in the treatment of chronic hepatitis B because
      of having potent antiviral effect and high genetic barriers against resistance.
      We aimed to compare efficacy of these drugs and to evaluate predictors of viral
      suppression. METHODS: This multicenter retrospective study was conducted in
      nucleos(t)ide analogue-naive chronic hepatitis B (CHB) patients from different 6
      centers. RESULTS: Of the 252 patients, 166 received ETV and 86 TDF. The two
      groups were similar in terms of age, gender, baseline ALT levels and fibrosis
      scores. ETV had significantly higher baseline HBV DNA, histological activity
      index and lower hepatitis B early antigen (HBeAg) seropositivity. Treatment
      duration was longer in ETV group (P<0.001). In univariate analysis, undetectable
      HBV DNA and ALT normalization rates were detected significantly higher in ETV
      groups (P<0.001 and 0.049, respectively). There was no significant difference
      between groups in terms of HBeAg seroconversion, virological breakthrough, time
      to virological breakthrough and time to ALT normalization. Entecavir was more
      effective in reducing HBV DNA levels at the 3rd, 6th and 12th months of the
      treatment (P=0.06, 0.021 and 0.012, respectively). However, multivariate Cox
      regression analysis indicated that TDF therapy compared to ETV had an increased
      probability of achieving complete viral suppression (HR=1, 66; 95% CI 1.21-2.33;
      P=0.010). Hepatitis B surface antigen (HBsAg) seroconversion was occurred in only
      one patient in ETV group. CONCLUSION: ETV leads to an early response on HBV DNA
      decline in the first year of the treatment. However, TDF is more successful than
      entecavir in achieving virological suppression.

PMID- 28757049
TI  - Polymorphic gastric lesions and hemorrhage after first dose of chemotherapy in a
      child with diffuse large B-cell lymphoma.

PMID- 28757050
TI  - Electroencephalographic, cognitive, and neurochemical effects of LY3130481 (CERC
      611), a selective antagonist of TARP-gamma8-associated AMPA receptors.
AB  - 6-[(1S)-1-[1-[5-(2-hydroxyethoxy)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3
      benzothiazol-2-one (LY3130481 or CERC-611) is a selective antagonist of AMPA
      receptors containing transmembrane AMPA receptor regulatory protein (TARP) gamma
      8. This molecule has been characterized as a potent and efficacious
      anticonvulsant in an array of acute and chronic epilepsy models in rodents. The
      present set of experiments was designed to assess the effects of LY3130481 on the
      electroencephelogram (EEG), cognitive function, and neurochemical outflow.
      LY3130481 disrupted food-maintained responding in rats and spontaneous
      alternation in a Y-maze in mice. In rat fear conditioning, LY3130481 caused a
      deficit in trace (hippocampal-dependent), but not in delay fear conditioning.
      Although these effects on cognitive performances were observed, the known
      cognitive-impairing anticonvulsant, topiramate, did not always produce deficits
      under these assay conditions. LY3130481 produced modest increases in wake times
      in rats. In addition, LY3130481 was able to attenuate some impairing effects of
      standard antiepileptic drugs. The motor-impairing effects of the lacosamide were
      attenuated by LY3130481 as was the decrease in non-rapid-eye movement sleep
      induced by carbamazepine. Evaluation of the effect of LY3130481 on
      neurotransmitter and metabolite efflux in the rat medial prefrontal cortex, using
      in vivo microdialysis, revealed significant increases in the pro-cognitive and
      wake-promoting neurotransmitters, histamine and acetylcholine, as well as in
      serotonin, telemethylhistamine, 5-HIAA, HVA and MHPG. LY3130481 thus presents a
      novel behavioral profile that will have to be evaluated in patients to fully
      appreciate its implications for therapeutics. LY3130481 is currently under
      clinical development as CERC-611 as an antiepileptic.

PMID- 28757051
TI  - Physiological and pharmacological properties of inhibitory postsynaptic currents
      mediated by alpha5beta1gamma2, alpha5beta2gamma2 and alpha5beta3gamma2 GABAA
      receptors.
AB  - alpha5-containing GABAARs are potential therapeutic targets for clinical
      conditions including age-related dementia, stroke, schizophrenia, Down syndrome,
      anaesthetic-induced amnesia, anxiety and pain. alpha5-containing GABAARs are
      expressed in layer 5 cortical neurons and hippocampal pyramidal neurons where
      they mediate both tonic currents and slow inhibitory postsynaptic currents
      (IPSCs). A range of drugs has been developed to specifically modulate these
      receptors. The main alpha5-containing GABAARs that are likely to exist in vivo
      are the alpha5beta1gamma2, alpha5beta2gamma2 and alpha5beta3gamma2 isoforms. We
      currently have few clues as to how these isoforms are distributed between
      synaptic and extrasynaptic compartments or their relative roles in controlling
      neuronal excitability. Accordingly, the aim of this study was to define the basic
      biophysical and pharmacological properties of IPSCs mediated by the three
      isoforms in a hippocampal neuron-HEK293 cell co-culture assay. The IPSC decay
      time constants were slow (alpha5beta1gamma2L: 45 ms; alpha5beta1gamma2L: 80 ms;
      alpha5beta3gamma2L: 184 ms) and were largely dominated by the intrinsic channel
      deactivation rates. By comparing IPSC rise times, we inferred that
      alpha5beta1gamma2L GABAARs are located postsynaptically whereas the other two are
      predominantly perisynaptic. alpha5beta3gamma2L GABAARs alone mediated tonic
      currents. We quantified the effects of four alpha5-specific inverse agonists (TB
      21007, MRK-016, alpha5IA and L-655708) on IPSCs mediated by the three isoforms.
      All compounds selectively inhibited IPSC amplitudes and accelerated IPSC decay
      rates, albeit with distinct isoform specificities. MRK-016 also significantly
      accelerated IPSC rise times. These results provide a reference for future studies
      seeking to identify and characterize the properties of IPSCs mediated by alpha5
      containing GABAAR isoforms in neurons.

PMID- 28757052
TI  - WITHDRAWN: Genetics update: Monogenetics, polygene disorders and the quest for
      modifying genes.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      https://doi.org/10.1016/j.neuropharm.2017.10.013. The duplicate article has
      therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be
      found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

PMID- 28757053
TI  - Cryopreservation of Indian red jungle fowl (Gallus gallus murghi) semen with
      polyvinylpyrrolidone.
AB  - The Indian red jungle fowl is a sub-species of the genus Gallus native to South
      Asia; facing high risk of extinction in its native habitat. During
      cryopreservation, permeable cryoprotectants like glycerol are usually employed
      and we previously showed encouraging results with 20% glycerol. Because bird
      spermatozoa contain very little intracellular water, the possibility of replacing
      an internal cryoprotectant by an external one is opened. In the present study, we
      tested the replacement of internal cryoprotectant glycerol by the external
      cryoprotectant Polyvinylpyrrolidone (PVP). PVP is a non-permeable cryoprotectant
      and keeps the sperm in glassy state both in cooling and warming stages without
      making ice crystallization within the sperm cell. We evaluated the effect of
      various levels of polyvinylpyrrolidone (PVP) on Indian red jungle fowl semen
      quality and fertility outcomes. The qualifying semen ejaculates collected from
      eight mature cocks were pooled, divided into five aliquots, diluted (37  degrees
      C) with red fowl semen extender having PVP [0% (control) 4% (w/v), 6% (w/v), 8%
      (w/v) and 10% (w/v)]. Diluted semen was cryopreserved and stored in liquid
      nitrogen. The whole experiment was repeated/replicated for five times
      independently. Sperm motility, plasma membrane integrity, viability and acrosome
      integrity were recorded highest (P < 0.05) with 6% PVP at post-dilution, cooling,
      equilibration and freeze-thawing. Higher (P < 0.05) no. of fertile eggs,
      fertility, no. of hatched chicks, percent hatch and hatchability was recorded
      with 6% PVP compared to control. It is concluded that 6% PVP maintained better
      post-taw quality and fertility of Indian red jungle fowl spermatozoa than
      glycerol and can be used in routine practice avoiding the contraceptive effects
      of glycerol.

PMID- 28757054
TI  - Late Dacron Patch Inflammatory Reaction after Carotid Endarterectomy.
AB  - OBJECTIVE: The aim was to analyse the incidence and presentation of carotid patch
      inflammatory reactions following carotid endarterectomy (CEA). METHODS: This was
      a cohort study using a prospectively maintained database. All patients who
      underwent elective CEA at a tertiary vascular centre between 2002 and 2016 were
      included. Computed tomography scan angiogram, duplex scan, and leucocyte
      scintigraphy were used to assess patients with suspected inflammatory patch
      complications. Re-intervention procedures and outcomes were noted. Histopathology
      and organisms cultured from the harvested material during re-intervention were
      assessed. RESULTS: During the study period, 633 patients underwent elective CEA.
      Fifty-one underwent eversion endarterectomy: 111 did not require a patch, whereas
      471 patients had a patch repair. Four hundred and twenty eight had a Dacron patch
      repair and 43 a biological patch. Eight patients returned with late Dacron patch
      inflammatory complications (1.3% of all CEA and 1.9% of Dacron patch closures)
      after a period ranging from 18 months to 7 years (mean 4.1 +/- 2.1 years). Seven
      of the eight patients underwent surgical re-intervention, and the eighth patient
      was deemed high surgical risk. One patient underwent a vein bypass, three had
      vein patch repair, one required internal carotid artery (ICA) ligation after
      patch excision, and two were managed by debridement, with omohyoid and
      sternomastoid muscle covering of the patch. The patient who required ICA ligation
      suffered a fatal stroke. The remaining patients had a satisfactory outcome. All
      patients showed evidence of foreign body reaction in pathological examination
      with no pathological organism cultured from swabs or tissue harvested during
      surgery. CONCLUSION: Late wound complications after CEA may be related to
      inflammatory reaction of the Dacron patch rather than infection. Infection should
      be excluded first. Reconstruction with vein is effective. However, debridement
      with sternomastoid and omohyoid muscle covering of the patch may be considered in
      high risk patients after exclusion of infection with regular follow-up.

PMID- 28757055
TI  - Deep Venous Procedures Performed in the National Health Service in England
      between 2005 and 2015.
AB  - OBJECTIVES: Recent advances in imaging technology and endovenous interventions
      have revolutionised the management of specific groups of patients with deep
      venous pathology. This study aimed to examine data published by Hospital Episode
      Statistics (HES) to assess trends in the number of endovascular and open surgical
      deep venous procedures performed in National Health Service (NHS) hospitals in
      England between 2005 and 2015. MATERIALS AND METHODS: The main diagnosis of deep
      venous thrombosis (DVT), and total number of primary open and percutaneous
      procedures for deep venous pathology for patients admitted to the NHS hospitals
      in England from 2005 to 2015 were retrieved from the HES database and analysed.
      RESULTS: An overall declining trend in the annual number of admissions for a
      primary diagnosis of DVT was observed (linear regression r2 = 0.9, p < .0001).
      The number of open surgical procedures for removal of thrombus remained largely
      unchanged (range 26-70); the frequency of percutaneous procedures increased
      steadily over the study period (range 0-311). The number of open surgical
      procedures relating to the vena cava fell between 2005 and 2009, and remained
      around 50 per year thereafter. Annual numbers of cases of deep venous bypass
      (range 17-33) and venous valve surgery (range 8-47) remained similar in trend
      over this period. The number of vena cava stent (range 0-405), other venous stent
      (range 0-316), and percutaneous venoplasty (range 0-972) procedures increased
      over the first 5 years of the study period. CONCLUSIONS: There is an increasing
      trend in relation to endovenous procedures but not open surgery, being carried
      out for deep venous pathology in the last decade in NHS hospitals in England.
      Despite a number of limitations with HES, the increase in the number of
      endovenous procedures shown is likely to have significant implications for the
      provision of care and healthcare resources for patients with deep venous
      pathology.

PMID- 28757056
TI  - Long Non-coding RNA-mRNA Correlation Analysis Reveals the Potential Role of
      HOTAIR in Pathogenesis of Sporadic Thoracic Aortic Aneurysm.
AB  - OBJECTIVE/BACKGROUND: Long non-coding RNA (lncRNA) play important roles in many
      diseases. However, their roles in sporadic thoracic aortic aneurysm (STAA) are
      unclear. Therefore, the objective of this study was to construct an lncRNA-mRNA
      network and dissect lncRNAs that might contribute to the pathogenesis of STAA.
      METHODS: Differentially expressed lncRNAs and mRNAs between four ascending aortic
      specimens derived from STAA and four controls from patients who had undergone
      coronary artery bypass graft (CABG) were identified by microarray analysis. Gene
      Ontology (GO) enrichment and lncRNA-mRNA correlation analysis were implemented
      with differentially expressed genes. An lncRNA in the correlation network HOX
      transcript antisense intergenic RNA (HOTAIR) was selected as a candidate. HOTAIR
      expression was examined by quantitative real time polymerase chain reaction in
      STAA (n = 24) and controls (n = 24 [CABG, n = 22; heart transplant donors, n =
      2]). HOTAIR expression was knocked down with siRNA in order to evaluate its role
      in apoptosis, cell proliferation, and expression of collagen types I and III.
      RESULTS: Five percent of lncRNAs were significantly differentially expressed in
      STAA patient samples compared with controls. GO enrichment analysis suggested
      differentially expressed genes were significantly enriched in the process of
      extracellular matrix organisation and leukocyte migration. lncRNA-mRNA
      interaction network revealed HOTAIR was associated with genes involved in
      extracellular matrix organisation. Moreover, HOTAIR expression was significantly
      decreased in STAA specimens and it negatively correlated with aortic diameter.
      HOTAIR knockdown induced early and late apoptosis and reduced cell proliferation.
      Furthermore, both mRNA and protein levels of collagen types I and III expression
      were suppressed after HOTAIR knockdown. CONCLUSION: Transcriptomic and lncRNA
      mRNA correlation analysis revealed HOTAIR was downregulated in STAA and
      associated with genes involved in extracellular matrix remodelling. In vitro
      experiments confirmed that knockdown of HOTAIR could induce apoptosis and
      suppress collagen types I and III expression in human aortic smooth muscle cells.

PMID- 28757057
TI  - Socioeconomic factors influencing childhood vaccination in two northern Italian
      regions.
AB  - BACKGROUND: Infant vaccination rates have been declining in Italy over the past 5
      7years. The aims of this study were to assess the trend in the proportions of
      children unvaccinated at 24months old, to identify sociodemographic factors
      associated with non-vaccination; and to examine changes in parental attitudes to
      vaccination over time. METHODS: We conducted a population-based birth cohort
      study by combining existing electronic data sets. The study population consisted
      of children born from 1995 to 2010 in the Friuli-Venezia Giulia (FVG) region, and
      from 2007 to 2011 in part of the Emilia Romagna (ER) region, in north-eastern
      Italy. The immunization registers were linked with the medical birth registers,
      which contain sociodemographic data on both parents and the newborn.
      Unconditional logistic regressions were used to identify associations between
      vaccine uptake at 24months and maternal sociodemographic variables. RESULTS: Of
      145,571 babies born in FVG and 75,308 in ER, there were 4222 (1.9%) who had not
      been vaccinated at all, and 23,948 (11.0%) without the optional measles, mumps
      and rubella (MMR) vaccination. The number of unvaccinated infants increased over
      time. Mothers who were over 35 or under 25years old, unmarried, with a higher
      formal education, and citizens of highly-developed countries were less compliant
      with vaccination recommendations in both the regions. A cohort effect was
      observed in FVG, for both educational level and citizenship: babies born between
      1995 and 2000 to mothers without an Italian citizenship and with a lower formal
      education were more likely to refuse vaccination for their offspring, while this
      association was reversed between 2006 and 2010. CONCLUSIONS: Mothers who are
      Italian citizens and have a good formal education have begun to refuse
      vaccination for their children in recent years. Future public health action in
      this setting should target highly educated parents.

PMID- 28757059
TI  - Untangling the psychosocial predictors of HPV vaccination decision-making among
      parents of boys.
AB  - BACKGROUND: HPV vaccination uptake in boys is suboptimal in many jurisdictions,
      particularly in the absence of publicly funded HPV vaccination programs. Parents
      represent key decision-makers of HPV vaccination and their HPV vaccine decision
      making stage is influenced by multiple psychosocial determinants. Our objective
      was to assess the relationship between a broad range of psychosocial factors and
      parents of boys' HPV vaccine decision-making stage. METHODS: Data were collected
      through an online survey from a nationally representative sample of Canadian
      parents of boys in February (T1) and November 2014 (T2). We assessed a broad
      number of psychosocial factors including: socio-demographics, health behaviours
      and validated scales for assessing HPV knowledge, attitudes and beliefs. Parents
      selected their HPV vaccination adoption stage based on the Precaution Adoption
      Process Model (PAPM). Multinomial logistic regression was used to test the
      association between predictors and PAPM stage at T1 and T2. RESULTS: Discussion
      with a healthcare provider about the HPV vaccine and increased HPV knowledge was
      associated with increased odds of being in the more advanced PAPM stages.
      Increased perception of risks in the absence of HPV vaccination, increased
      perception that others endorse HPV vaccination and positive attitudes related to
      vaccines in general were associated with increased odds of being in the decided
      to vaccinate stage. Believing that HPV vaccination is harmful increased, and
      perceiving the benefits of HPV vaccination decreased the odds of deciding not to
      vaccinate. CONCLUSIONS: This study highlights the psychosocial predictors of the
      decision-making stage reported by parents regarding HPV vaccination of their
      sons, that were significant at two time-points. Targeted interventions that
      consider the impact of the health care provider and address knowledge gaps as
      well as individual beliefs about benefits, risks, and harms of the HPV vaccine
      and vaccines in general should be implemented to help parents make better
      informed decisions that is, to move closer to actual vaccination adoption.

PMID- 28757060
TI  - MMR and MMRV vaccines.
AB  - Measles, mumps, rubella and varicella are viral infections which can implicate
      seriously long-term sequelae of infected individuals or even the unborn child.
      Vaccines against the individual diseases have long been available. Global measles
      vaccination is estimated to have prevented more than 20million deaths during 2000
      2015. During the same time period, measles incidence decreased from 146 to 36
      cases per million populations. Today vaccinations against measles, mumps, rubella
      and varicella are now carried out mainly with combination vaccines. These are
      today known as immunogenic and safe. MMRV had similar immunogenicity and overall
      safety profiles to MMR administered with or without varicella vaccine. This issue
      provides a review of the different vaccines, mode of administration, catch up
      immunization and postexposure prophylaxis as well as contraindications and
      adverse effects of the immunization against measles, mumps, rubella, and
      varicella. The article presents an overview of important information of
      preventing these diseases with a focus on the existing combination vaccines.

PMID- 28757061
TI  - Radiosynthesis and evaluation of new PET ligands for peripheral cannabinoid
      receptor type 1 imaging.
AB  - Cannabinoid receptor type 1 (CB1) is mainly expressed in the brain, as well as
      being expressed in functional relevant concentrations in various peripheral
      tissues. 1-(4-Chlorophenyl)-3-(3-(6-(pyrrolidin-1-yl)pyridin-2-yl)phenyl)urea
      (PSNCBAM-1, 1) was developed as a potent allosteric antagonist for CB1 and its
      oral administration led to reductions in the appetite and body weight of rats.
      Several analogs of 1 (compounds 2 and 3) were recently identified through a
      series of structure-activity relationship studies. Herein, we report the
      synthesis of radiolabeled analogs of these compounds using [11C]COCl2 and an
      evaluation of their potential as PET ligands for CB1 imaging using in vitro and
      in vivo techniques. [11C]2 and [11C]3 were successfully synthesized in two steps
      using [11C]COCl2. The radiochemical yields of [11C]2 and [11C]3 were 17+/-8% and
      20+/-9% (decay-corrected to the end of bombardment, based on [11C]CO2). The
      specific activities of [11C]2 and [11C]3 were 42+/-36 and 37+/-13GBq/MUmol,
      respectively. The results of an in vitro binding assay using brown adipose tissue
      (BAT) homogenate showed that the binding affinity of 2 for CB1 (KD=15.3uM) was
      much higher than that of 3 (KD=26.0uM). PET studies with [11C]2 showed a high
      uptake of radioactivity in BAT, which decreased in animals pretreated with AM281
      (a selective antagonist for CB1). In conclusion, [11C]2 may be a useful PET
      ligand for imaging peripheral CB1 in BAT.

PMID- 28757058
TI  - Immune correlates of protection for dengue: State of the art and research agenda.
AB  - Dengue viruses (DENV1-4) are mosquito-borne flaviviruses estimated to cause up to
      ~400 million infections and ~100 million dengue cases each year. Factors that
      contribute to protection from and risk of dengue and severe dengue disease have
      been studied extensively but are still not fully understood. Results from Phase 3
      vaccine efficacy trials have recently become available for one vaccine candidate,
      now licensed for use in several countries, and more Phase 2 and 3 studies of
      additional vaccine candidates are ongoing, making these issues all the more
      urgent and timely. At the "Summit on Dengue Immune Correlates of Protection",
      held in Annecy, France, on March 8-9, 2016, dengue experts from diverse fields
      came together to discuss the current understanding of the immune response to and
      protection from DENV infection and disease, identify key unanswered questions,
      discuss data on immune correlates and plans for comparison of results across
      assays/consortia, and propose a research agenda for investigation of dengue
      immune correlates, all in the context of both natural infection studies and
      vaccine trials.

PMID- 28757062
TI  - Design, synthesis and biological evaluation of novel 3-oxo-4-oxa-5alpha-androst
      17beta-amide derivatives as dual 5alpha-reductase inhibitors and androgen
      receptor antagonists.
AB  - Prostate cancer (PCa) is the second leading cause of death in men. Recently, some
      researches have showed that 5alpha-reductase inhibitors were beneficial in PCa
      treatment as well. In this study, a series of novel 3-oxo-4-oxa-5alpha-androst
      17beta-amide derivatives have been designed and synthesized in a more simple and
      convenient method. Most of the synthesized compounds displayed good 5alpha
      reductase inhibitory activities and androgen receptor binding affinities. Their
      anti-proliferation activities in PC-3 and LNCaP cell lines were also evaluated
      and the results indicated that most of the synthesized compounds exhibited potent
      anti-proliferative activities. It is obvious that the androgen-dependent cell
      line LNCaP was much more sensitive than the androgen-independent cell line PC-3.
      Among all the synthesized compounds, 11d and 11k displayed the best inhibition
      activity with 4-fold more sensitive toward LNCaP than PC-3, which was consistent
      with their high affinities observed in AR binding assay. Molecular modeling
      studies suggested that 11k could bind to AR in a manner similar to the binding of
      dihydrotestosterone to AR. Compared to the finasteride, 11k showed a longer
      plasma half-life (4h) and a better bioavailability. Overall, based on biological
      activities data, compound 11d and 11k can be identified as potential dual 5alpha
      reductase inhibitors and AR antagonists which might be of therapeutic importance
      for prostate cancer treatment.

PMID- 28757064
TI  - Synthesis and anti-tumor evaluation of panaxadiol halogen-derivatives.
AB  - In the current work, 13 novel panaxadiol (PD) derivatives were synthesized by
      reacting with chloroacetyl chloride and bromoacetyl bromide. Their in vitro
      antitumor activities were evaluated on three human tumor cell lines (HCT-116, BGC
      823, SW-480) and three normal cells (human gastric epithelial cell line-GES-1,
      hair follicle dermal papilla cell line-HHDPC and rat myocardial cell line-H9C2)
      by MTT assay. Compared with PD, the results demonstrated that compound 1e, 2d, 2e
      showed significant anti-tumor activity against three tumor cell lines, the IC50
      value of compound 2d against HCT-116 was the lowest (3.836MUM). The anti-tumor
      activity of open-ring compounds are significantly better than the compounds of C
      25 cyclization. Compound 1f, 2f, 2g showed the strong anti-tumor activity. The
      IC50 value of compound 2g against BGC-823 and SW-480 were the lowest (0.6MUM and
      0.1MUM, respectively). Combined with cytotoxicity test, the IC50 value of
      compound 1e, 2d, 2e are greater than 100. the open-ring compounds (1f, 2f, 2g)
      showed a strong toxicity. The toxicity of 1f is lower than 2f and 2g. These
      compounds may be useful for the development of novel antiproliferative agents.

PMID- 28757065
TI  - Design and synthesis of piperazine acetate podophyllotoxin ester derivatives
      targeting tubulin depolymerization as new anticancer agents.
AB  - In this paper, a series of podophyllotoxin piperazine acetate ester derivatives
      were synthesized and investigated due to their antiproliferation activity on
      different human cancer cell lines. Among the congeners, C5 manifested prominent
      cytotoxicity towards the cancer cells, without causing damage on the non-cancer
      cells through inhibiting tubulin assembly and having high selectively causing
      damage on the human breast (MCF-7) cell line (IC50=2.78+/-0.15MUM). Treatments of
      MCF-7 cells with C5 resulted in cell cycle arrest in G2/M phase and microtubule
      network disruption. Moreover, regarding the expression of cell cycle relative
      proteins CDK1, a protein required for mitotic initiation was up-regulated.
      Besides, Cyclin A, Cyclin B1 and Cyclin D1 proteins were down-regulated.
      Meanwhile, it seems that the effect of C5 on MCF-7 cells apoptosis inducing was
      observed to be not obvious enough. In addition, docking analysis demonstrated
      that the congeners occupy the colchicine binding pocket of tubulin.

PMID- 28757063
TI  - ATP-competitive, marine derived natural products that target the DEAD box
      helicase, eIF4A.
AB  - Activation of translation initiation is a common trait of cancer cells. Formation
      of the heterotrimeric eukaryotic initiation factor F (eIF4F) complex is the rate
      limiting step in 5' m7GpppN cap-dependent translation. This trimeric complex
      includes the eIF4E cap binding protein, the eIF4G scaffolding protein, and the
      DEAD box RNA helicase eIF4A. eIF4A is an ATP-dependent helicase and because it is
      the only enzyme in the eIF4F complex, it has been shown to be a potential
      therapeutic target for a variety of malignancies. To this end, we have used a
      simple ATPase biochemical screen to survey several hundred marine and terrestrial
      derived natural products. Herein, we report the discovery of two natural products
      from marine sources, elisabatin A (1) and allolaurinterol (2), which show low uM
      inhibition of eIF4A ATPase activity. Enzymological analyses revealed 1 and 2 to
      be ATP-competitive, and cellular evaluations showed reasonable cytotoxicity
      against A549 (lung cancer) and MDA-MA-468 (breast cancer) cell lines. However,
      only compound 2 showed potent inhibition of helicase activity congruent with its
      ATPase inhibitory activity.

PMID- 28757066
TI  - Design, synthesis and biological evaluation of Lenalidomide derivatives as tumor
      angiogenesis inhibitor.
AB  - Lenalidomide is a type of immunomodulatory agent with anti-tumor activity by
      mainly expressed in the anti-angiogenesis. In order to enhance the
      pharmacological activity of Lenalidomide, a series of Lenalidomide derivatives
      were designed as tumor angiogenesis inhibitors. The potential anti-angiogenesis
      targets of Lenalidomide derivatives were virtual screened on Auto-Dock 4.0 by
      using reverse docking method. The six target proteins, such as vascular
      endothelial growth factor receptor, epidermal growth factor receptor, fibroblast
      growth factor receptor, BCR-ABL tyrosine kinase, p38 mitogen activated protein
      kinase and metal protein kinase, were chosen as the targets. The Lenalidomide
      derivatives were synthesized by alkylated, acylated or sulfonylated Lenalidomide
      and verified by the 1H NMR, 13C NMR and LC-MS. Their anti-cancer activities were
      detected by using CCK-8 in the esophageal carcinoma cell line EC9706. The results
      indicate that the inhibitory activities of Lenalidomide derivatives were higher
      than that of Lenalidomide.

PMID- 28757067
TI  - Discovery of novel 4(1H)-quinolone derivatives as potential antiproliferative and
      apoptosis inducing agents.
AB  - A series of novel 4(1H)-quinolone derivatives was synthesized and evaluated for
      antiproliferative activity in vitro. The results showed that these compounds
      exhibited more potent antiproliferative effect against a panel of human
      tumorcelllines than the lead compound 7-chloro-4(1H)-quinolone 1. Compound 7e was
      found to be the most potent antiproliferative agent and to exhibit selective
      cytotoxic activity against HepG2 cell lines with IC50 value lower than 1.0MUM.
      Annexin V/FITC-PI assay showed that compound 7e induced apoptosis in HepG2 cells
      with a dose-dependent manner. Western blotting analysis indicated that compound
      7e induced cell cycle arrest in G2/M phase by p53-depedent pathway.

PMID- 28757068
TI  - Chemical composition and antifungal activity of the essential oil of Zhumeria
      majdae, Heracleum persicum and Eucalyptus sp. against some important
      phytopathogenic fungi.
AB  - Application of essential oils of medicinal plants is considered a safe and
      acceptable method for plant disease management to protect plants from pathogenic
      microorganisms. Thus, in recent study, essential oils (EOs) from Zhumeria majdae,
      Heracleum persicum (two Iranian endemic plants) and Eucalyptus sp. were assayed
      for their antifungal potential against ten phytopathogenic fungi, including
      Fusarium graminearum, Fusarium asiaticum, Fusarium redolens f.sp. dianthus,
      Fusarium verticillioides, Fusarium oxysporum f.sp. lentis, Sclerotinia
      sclerotiorum, Aspergillus flavus, Aspergillus tubingensis, Botrytis cinerea and
      Cladosporium cladosporioides. Chemical composition of these oils was identified
      by GC-MS analysis. Based on our results, Z. majdae essential oil exhibited the
      best antifungal activity among tested essential oils, completely inhibiting
      growth of five fungal species. EOs of Eucalyptus sp. and H. persicum showed
      moderate and poor antifungal capacity, respectively. GC-MS analysis demonstrated
      that linalool and camphor were the main components of the essential oils of Z.
      majdae; furthermore, 1,8-cineole and hexyl ester formed the major portions of
      Eucalyptus sp. and H. persicum EOs. Due to the significant inhibition of some
      EOs, additional research about their use for control of plant diseases caused by
      these fungi is recommended.

PMID- 28757070
TI  - Individual differences in the processing of smoking-cessation video messages: An
      imaging genetics study.
AB  - Studies testing the benefits of enriching smoking-cessation video ads with
      attention-grabbing sensory features have yielded variable results. Dopamine
      transporter gene (DAT1) has been implicated in attention deficits. We
      hypothesized that DAT1 polymorphism is partially responsible for this
      variability. Using functional magnetic resonance imaging, we examined brain
      responses to videos high or low in attention-grabbing features, indexed by
      "message sensation value" (MSV), in 53 smokers genotyped for DAT1. Compared to
      other smokers, 10/10 homozygotes showed greater neural response to High- vs. Low
      MSV smoking-cessation videos in two a priori regions of interest: the right
      temporoparietal junction and the right ventrolateral prefrontal cortex. These
      regions are known to underlie stimulus-driven attentional processing. Exploratory
      analysis showed that the right temporoparietal response positively predicted
      follow-up smoking behavior indexed by urine cotinine. Our findings suggest that
      responses to attention-grabbing features in smoking-cessation messages is
      affected by the DAT1 genotype.

PMID- 28757072
TI  - Commentary on: Association of imaging abnormalities of the subcallosal septal
      area with Alzheimer's disease and mild cognitive impairment.

PMID- 28757073
TI  - Chaotic provinces in the kingdom of the Red Queen.
AB  - The interplay between parasites and their hosts is found in all kinds of species
      and plays an important role in understanding the principles of evolution and
      coevolution. Usually, the different genotypes of hosts and parasites oscillate in
      their abundances. The well-established theory of oscillatory Red Queen dynamics
      proposes an ongoing change in frequencies of the different types within each
      species. So far, it is unclear under what conditions Red Queen dynamics persists,
      especially when the number of types per species increases. Some models show that
      with many types of hosts and parasites or more species chaotic dynamics occur. In
      our analysis, an arbitrary number of types within two species are examined in a
      deterministic framework with constant or changing population size and very simple
      interactions. This general framework allows for analytical solutions for internal
      fixed points and their stability. The numerical analysis shows that for two
      species, once more than two types are considered per species, irregular dynamics
      in their frequencies can be observed in the long run. The nature of the dynamics
      depends strongly on the initial configuration of the system; the usual regular
      Red Queen oscillations are only observed when all types initially have similar
      abundance.

PMID- 28757071
TI  - Individual differences in early adolescents' latent trait cortisol: Interaction
      of early adversity and 5-HTTLPR.
AB  - The present study aimed to examine the interaction of 5-HTTLPR and early
      adversity on trait-like levels of cortisol. A community sample of 117 early
      adolescent girls (M age=12.39years) provided DNA samples for 5-HTTLPR genotyping,
      and saliva samples for assessing cortisol 3 times a day (waking, 30min post
      waking, and bedtime) over a three-day period. Latent trait cortisol (LTC) was
      modeled using the first 2 samples of each day. Early adversity was assessed with
      objective contextual stress interviews with adolescents and their mothers. A
      significant 5-HTTLPR*early adversity interaction indicated that greater early
      adversity was associated with lower LTC levels, but only among individuals with
      either L/L or S/L genotype. Findings suggest that serotonergic genetic variation
      may influence the impact of early adversity on individual differences in HPA-axis
      regulation. Future research should explore whether this interaction contributes
      to the development of psychopathology through HPA axis functioning.

PMID- 28757074
TI  - Demographic noise slows down cycles of dominance.
AB  - We study the phenomenon of cyclic dominance in the paradigmatic Rock-Paper
      Scissors model, as occurring in both stochastic individual-based models of finite
      populations and in the deterministic replicator equations. The mean-field
      replicator equations are valid in the limit of large populations and, in the
      presence of mutation and unbalanced payoffs, they exhibit an attracting limit
      cycle. The period of this cycle depends on the rate of mutation; specifically,
      the period grows logarithmically as the mutation rate tends to zero. We find that
      this behaviour is not reproduced in stochastic simulations with a fixed finite
      population size. Instead, demographic noise present in the individual-based model
      dramatically slows down the progress of the limit cycle, with the typical period
      growing as the reciprocal of the mutation rate. Here we develop a theory that
      explains these scaling regimes and delineates them in terms of population size
      and mutation rate. We identify a further intermediate regime in which we
      construct a stochastic differential equation model describing the transition
      between stochastically-dominated and mean-field behaviour.

PMID- 28757076
TI  - Memoryless disturbance-observer-based adaptive tracking of uncertain pure
      feedback nonlinear time-delay systems with unmatched disturbances.
AB  - This paper presents a delay-independent nonlinear disturbance observer (NDO)
      design methodology for adaptive tracking of uncertain pure-feedback nonlinear
      systems in the presence of unknown time delays and unmatched external
      disturbances. Compared with all existing NDO-based control results for uncertain
      lower-triangular nonlinear systems where unknown time delays have been not
      considered, the main contribution of this paper is to develop a delay-independent
      design strategy to construct an NDO-based adaptive tracking scheme in the
      presence of unknown time-delayed nonlinearities and non-affine nonlinearities
      unmatched in the control input. The proposed delay-independent scheme is
      constructed by employing the appropriate Lyapunov-Krasovskii functionals and the
      same function approximators for the NDO and the controller. It is shown that all
      the signals of the closed-loop system are semi-globally uniformly ultimately
      bounded and the tracking error converges to an adjustable neighborhood of the
      origin.

PMID- 28757077
TI  - An improved stopping condition guarantee recovery of sparse signal via Subspace
      Pursuit method.
AB  - The Subspace Pursuit (SP) algorithm is one of greedy pursuit methods which is
      used to reconstruct of K-sparse signal. Unlike existing condition produced by Dai
      and Milenkovic in 2004 that suggests the residual value of current iteration is
      reduced from the previous iteration, our approach eliminates useless information
      by reducing the number of iterations used to detect the correct support set. This
      operation is done by suggesting a new halting condition that can capture the best
      support set which can give the best representation of the reconstructed signal.
      The new halting conditions enhanced the SP algorithm to low computational
      complexity and reconstruction accuracy of the sparse signal. A mathematically
      proven for two halt condition: noiseless setting, and noisy setting for signal
      affected by Gaussian noise. An error bound relation also is driven. In this
      paper, we try also to relax the restricted isometry constant RIC value to narrows
      the gap between the known bounds and ultimate performance, which it produced by
      Dai. Simulation results show that the new halting condition can overpass best
      results produce by earlier iteration and rise time consume. Our new halting
      condition can catch this earlier iteration and enhanced SP algorithm results.

PMID- 28757075
TI  - DNA demethylation pattern of in-vitro fertilized and cloned porcine pronuclear
      stage embryos.
AB  - Recent studies in mice showed that the Ten-eleven translocation Enzymes (TET)
      family is involved in the active DNA demethylation. The isotype TET-3 is
      responsible for the conversion of 5mc (5-methylcytosine) to 5hmc (5
      hydroxymethylcytosine) at the pronuclear stages of mouse embryo. This study was
      performed to investigate the pattern of methylation change and the role of TET
      family in the demethylation process of porcine in-vitro fertilization (IVF) and
      somatic cell nuclear transfer (SCNT) derived embryo. Bisulfite-sequencing PCR
      (BSP) and DNA glucosylation and digestion before quantitative PCR (qGluMS-PCR)
      were done to evaluate the exact change of methylation during porcine pronuclear
      stages. The results showed that the amount of 5hmc detected increased whereas 5mc
      decreased in IVF embryo from pronuclear stage 2 (PN2) to pronuclear stage 5
      (PN5). In addition, Immunofluorescent staining showed that the 5hmc signal, also
      detected in oocytes, significantly increased in both pronucleus from
      fertilization to PN2. The amount of 5hmc continued to rise in male pronucleus but
      decreased to a very low level in female pronucleus from PN2 to PN5. The above
      results indicate that female pronucleus might undergo active demethylation only
      at early pronuclear stages. On the other hand, male pronucleus might undergo
      active demethylation throughout all pronuclear stages. The expression of three
      TET isotypes (TET-1, TET-2, TET-3) were tested and TET-3 was found to be the
      highest expressed isotype. High TET-3 concentrations observed mainly in male
      pronucleus using immunofluorescent staining, implying that TET-3 might be the
      main enzyme which catalyzes the conversion of 5mc to 5hmc. In contrast, no TET-3
      signal was detected in female pronucleus through the pronuclear stages. The
      demethylation pattern of SCNT embryos resembled that of the male pronucleus of
      IVF embryos, suggesting that active demethylation might happen in porcine cloned
      embryo.

PMID- 28757069
TI  - Structural Foundations of RNA Silencing by Argonaute.
AB  - Nearly every cell in the human body contains a set of programmable gene-silencing
      proteins named Argonaute. Argonaute proteins mediate gene regulation by small
      RNAs and thereby contribute to cellular homeostasis during diverse physiological
      process, such as stem cell maintenance, fertilization, and heart development.
      Over the last decade, remarkable progress has been made toward understanding
      Argonaute proteins, small RNAs, and their roles in eukaryotic biology. Here, we
      review current understanding of Argonaute proteins from a structural prospective
      and discuss unanswered questions surrounding this fascinating class of enzymes.

PMID- 28757078
TI  - Robust output synchronization of heterogeneous nonlinear agents in uncertain
      networks.
AB  - This paper investigates the global robust output synchronization problem for a
      class of nonlinear multi-agent systems. In the considered setup, the controlled
      agents are heterogeneous and with both dynamic and parametric uncertainties, the
      controllers are incapable of exchanging their internal states with the neighbors,
      and the communication network among agents is defined by an uncertain simple
      digraph. The problem is pursued via nonlinear output regulation theory and
      internal model based design. For each agent, the input-driven filter and the
      internal model compose the controller, and the decentralized dynamic output
      feedback control law is derived by using backstepping method and the modified
      dynamic high-gain technique. The theoretical result is applied to output
      synchronization problem for uncertain network of Lorenz-type agents.

PMID- 28757079
TI  - Tracheal diverticula in advanced cystic fibrosis: Prevalence, features, and
      outcomes after lung transplantation.
AB  - BACKGROUND: Tracheal diverticula (TD) are rare anomalies that may harbor infected
      secretions, posing potential risk to patients with lung disease. In an end-stage
      cystic fibrosis (CF) cohort, we describe the characteristics and associated post
      lung transplant (LTx) outcomes of TD. METHODS: Pre-transplant computed tomography
      (CT)'s were reviewed in CF patients undergoing LTx. TD were characterized
      radiographically and on autopsy when available. Pre-transplant clinical variables
      and post-transplant outcomes were compared by TD status. RESULTS: Of 93 patients,
      35 (37.6%) had TD. 58% of TD had fat-stranding, and post-mortem TD examinations
      revealed histology carrying intense submucosal inflammation, and purulent
      contents that cultured identical species to sputum. There was no difference in
      post-LTx survival [HR 1.77 (0.82-3.82), p=0.147], bacterial re-colonization, or
      rejection in patients with TD compared to those without. Patients with TD were
      more likely to die from infection, but the result was not statistically
      significant [HR 2.02 (0.62-6.63), p=0.245]. CONCLUSIONS: We found a high
      prevalence of TD in end-stage CF, where diverticula may represent a large-airway
      bacterial reservoir. TD were not associated with differences in post-LTx
      outcomes, but given the infectious concerns further investigation is necessary.

PMID- 28757080
TI  - A Fusion Receptor as a Safety Switch, Detection, and Purification Biomarker for
      Adoptive Transferred T Cells.
AB  - The incorporation of an endogenous safety switch represents a rational strategy
      for the control of toxicities following the administration of adoptive T cell
      therapies. An ideal safety switch should be capable of depleting the transferred
      T cells with minimal injury to normal tissues. We generated a fusion receptor by
      engineering a cryptic 806 epitope of human epidermal growth factor receptor
      (EGFR) into the N terminus of the full-length human folate receptor 1 (FOLR1),
      designated as FR806. The expression of FR806 allows transduced T cells to be
      targeted with CH12, a monoclonal antibody recognizing the 806 epitope, but not
      wild-type EGFR in healthy tissues. FR806, therefore, constitutes a specific cell
      surface marker for the elimination of transduced T cells. We demonstrate that the
      antibody-drug conjugate (ADC) CH12-MMAF is efficiently internalized by FR806
      expressing T cells and has the potential to eliminate them. Transfected T cells
      could, furthermore, be efficiently detected and purified using CH12 antibodies.
      In immuno-compromised mice, CH12-MMAF eliminated the majority of transferred T
      cells expressing FR806 and anti-CD19 chimeric antigen receptor (CAR). The
      selectivity for the 806 epitope and internalization capacity of FOLR1 makes FR806
      an efficient safety switch, which may additionally be used as a detection and
      purification biomarker for human T cell immunotherapies.

PMID- 28757082
TI  - A proposal for the eradication of Middle East respiratory syndrome.

PMID- 28757081
TI  - Geographic tongue: assessment of peripheral nerve status, Langerhans cell, and
      HLA-DR expression.
AB  - OBJECTIVES: The objectives of this study were to determine whether geographic
      tongue (GT) is an antigen-driven condition by assessing Langerhans cell numbers
      and the expression of human leukocyte antigen (HLA)-DP, -DQ, and -DR in the
      epithelium of GT and to assess peripheral nerve status for any possible
      damage/injury association by quantifying neurite area in connective tissue in GT.
      STUDY DESIGN: Randomly selected samples of GT were examined by using routine
      immunoperoxidase staining methods to S100 protein, neurofilament, CD1a, and HLA
      class II. The Student t test and Mann-Whitney U test were used to assess
      statistical significance. RESULTS: Langerhans cell numbers were found to be
      increased in GT. HLA expression was also seen in Langerhans cells and
      inflammatory cells and in the spinous layer and parabasal epithelial cells in 2
      samples of GT. Total nerve tissue, based on area measurements, was not
      significantly different between GT and control tissues. CONCLUSIONS: The increase
      in Langerhans cells suggests that GT is a condition that is likely driven by an
      unknown external antigen. Peripheral nerve damage was not apparent, suggesting
      that this is not a mechanism whereby patients with GT become symptomatic.

PMID- 28757083
TI  - Underutilization of norovirus testing in hematopoietic cell transplant recipients
      at a large cancer center.
AB  - The development of a new laboratory-developed norovirus assay provided an
      opportunity to assess testing patterns, incidence, and outcomes of norovirus
      among hematopoietic cell transplant (HCT) recipients. Clostridium difficile and
      norovirus tests from 1,393 HCT recipients were compared in these analyses. In
      this population of high-risk patients, norovirus appeared to occur seasonally,
      but testing was infrequent despite a correlation with more severe disease when
      compared with patients with C difficile infection.

PMID- 28757084
TI  - Outbreak of health care-associated Burkholderia cenocepacia bacteremia and
      infection attributed to contaminated sterile gel used for central line insertion
      under ultrasound guidance and other procedures.
AB  - BACKGROUND: We report an outbreak of Burkholderia cenocepacia bacteremia and
      infection in 11 patients predominately in intensive care units caused by
      contaminated ultrasound gel used in central line insertion and sterile procedures
      within 4 hospitals across Australia. METHODS: Burkholderia cenocepacia was first
      identified in the blood culture of a patient from the intensive care unit at the
      Gold Coast University Hospital on March 26, 2017, with 3 subsequent cases
      identified by April 7, 2017. The outbreak response team commenced investigative
      measures. RESULTS: The outbreak investigation identified the point source as
      contaminated gel packaged in sachets for use within the sterile ultrasound probe
      cover. In total, 11 patient isolates of B cenocepacia with the same multilocus
      sequence type were identified within 4 hospitals across Australia. This typing
      was the same as identified in the contaminated gel isolate with single nucleotide
      polymorphism-based typing, demonstrating that all linked isolates clustered
      together. CONCLUSION: Arresting the national point-source outbreak within
      multiple jurisdictions was critically reliant on a rapid, integrated, and
      coordinated response and the use of informal professional networks to first
      identify it. All institutions where the product is used should look back at
      Burkholderia sp blood culture isolates for speciation to ensure this outbreak is
      no larger than currently recognized given likely global distribution.

PMID- 28757085
TI  - Effect of automated ultraviolet C-emitting device on decontamination of hospital
      rooms with and without real-time observation of terminal room disinfection.
AB  - BACKGROUND: We studied the effectiveness of an ultraviolet C (UV-C) emitter in
      clinical settings and compared it with observed terminal disinfection. METHODS:
      We cultured 22 hospital discharge rooms at a tertiary care academic medical
      center. Phase 1 (unobserved terminal disinfection) included cultures of 11 high
      touch environmental surfaces (HTSs) after terminal room disinfection (AD) and
      after the use of a UV-C-emitting device (AUV). Phase 2 (observed terminal
      disinfection) included cultures before terminal room disinfection (BD), AD, and
      AUV. Zero-inflated Poisson regression compared mean colony forming units (CFU)
      between the groups. Two-sample proportion tests identified significance of the
      observed differences in proportions of thoroughly cleaned HTSs (CFU < 5).
      Significant P value was determined using the Bonferroni corrected threshold of
      alpha = .05/12 = .004. RESULTS: We obtained 594 samples. Risk of overall
      contamination was 0.48 times lower in the AUV group than in the AD group (P <
      .001), with 1.04 log10 reduction. During phase 1, overall proportion of HTSs with
      <5 CFUs increased in AUV versus AD by 0.12 (P = .001). During phase 2, it
      increased in AD versus BD by 0.45 (P < .001), with no significant difference
      between AD and AUV (P = .02). CONCLUSIONS: Use of UV-C with standard cleaning
      significantly reduced microbial burden and improved the thoroughness of terminal
      disinfection. We found no further benefit to UV-C use if standard terminal
      disinfection was observed.

PMID- 28757086
TI  - Multidrug-resistant Acinetobacter: Risk factors and outcomes in veterans with
      spinal cord injuries and disorders.
AB  - BACKGROUND: Multidrug-resistant (MDR) Acinetobacter is a growing concern and has
      been identified as a serious threat by the Centers for Disease Control and
      Prevention. However, there is little information on MDR Acinetobacter in
      individuals with spinal cord injuries and disorders (SCI/Ds). Therefore, the
      objective of this study was to identify risk factors for, and assess outcomes of,
      MDR Acinetobacter in veterans with SCI/Ds. METHODS: This was a retrospective
      cohort study from January 1, 2012-December 31, 2013, using national Veterans
      Affairs medical encounter and microbiology data. RESULTS: A total of 773
      Acinetobacter cultures were identified in 571 patients, of which 58.9% were MDR.
      Inpatient culture, sputum and other specimen type, receipt of antibiotics within
      90 days before culture date, and pressure ulcers were identified as independent
      predictors of MDR Acinetobacter. Highest odds of MDR Acinetobacter were seen with
      previous antibiotic use (odds ratio, 7.27; 95% confidence interval, 2.59-20.54).
      Thirty-day mortality was 5.3% in this study. Multidrug resistance, previous
      mechanical ventilation 90 days before the culture, and cancer were all
      independent risk factors for 30-day mortality. CONCLUSIONS: There should be
      increased efforts to highlight the importance of antimicrobial stewardship to
      improve infection control to help limit spread of Acinetobacter in health care
      settings.

PMID- 28757087
TI  - Associations between antimicrobial stewardship program elements and Clostridium
      difficile infection performance.
AB  - Hospitals are categorized as better, no different, or worse at a national level
      based on their Clostridium difficile infection performance. Institutional
      antimicrobial stewardship programs seek to decrease the occurrence of C difficile
      by implementing strategies to address antibiotic usage; however, optimal
      structure and strategies for accomplishing this remain largely unknown. We found
      that a higher proportion of hospitals with either a worse or no different rank
      used a postprescription audit and feedback strategy than hospitals with a better
      rank.

PMID- 28757088
TI  - Emergence of carbapenem-resistant Enterobacteriaceae in Orange County,
      California, and support for early regional strategies to limit spread.
AB  - BACKGROUND: The east-to-west spread of carbapenem-resistant Enterobacteriaceae
      (CRE) represents an opportunity to explore strategies to limit spread in
      nonendemic areas. We evaluated CRE emergence and regional support for containment
      strategies. METHODS: A 17-question cross-sectional survey was administered to
      infection prevention programs in Orange County, CA (31 hospitals serving 3
      million residents), between January and September 2014. Questions addressed newly
      detected hospital- and community-onset CRE cultures (2008-2013), current CRE
      control strategies, and support for prevention strategies for a hypothetical
      regional intervention. RESULTS: Among 31 hospitals, 21 (68%, representing 17
      infection prevention programs) completed the survey. CRE was scarcely detected
      between 2009-2010; within 4 years, 90% of hospitals reported CRE, with 2.5-fold
      higher community-onset than hospital-onset CRE. Between 2011 and 2013, annual CRE
      incidence increased 4.7-fold (1.4-6.3 cases/10,000 admissions). Support for a
      regional CRE prevention bundle was unanimous. Although 22% bathed patients
      positive for CRE with chlorhexidine gluconate and 11% actively screened for CRE,
      86% and 57%, respectively, would consider these strategies in a regional
      intervention. CONCLUSIONS: CRE epidemiology in Orange County parallels early
      progression previously seen in now-endemic areas, representing an opportunity to
      consider interventions to prevent endemic spread. Many facilities would consider
      proactive strategies, such as chlorhexidine bathing, in the setting of a regional
      collaborative.

PMID- 28757089
TI  - High-risk patients with mild-moderate left ventricular dysfunction after a
      previous myocardial infarction. A long-term prognostic data by cardiac magnetic
      resonance.
AB  - BACKGROUND: Few studies have explored prognosis in patients with previous
      myocardial infarction (MI) with mild-moderate (MM) left ventricular (LV)
      dysfunction (D). The aim of our study was to investigate whether combining LV
      parameters obtained by cardiac magnetic resonance (CMR) improves risk
      stratification of patients with previous MI and MM-LV-D. METHODS: In 418
      consecutive patients (63.3+/-11.3years old, female 12.9%) with previous MI, we
      quantified LVEF, volumes and wall motion score index (WMSI) and measured the
      infarct extent by late gadolinium enhancement (LGE). According to LVEF, patients
      were considered with normal LVEF (>55%), MM-LV-D (LVEF>30 and <=55%) and severe
      (S) LV-D (LVEF <=30). RESULTS: During follow-up (median, 39.7months) cardiac
      events (cardiac death or appropriate intra-cardiac defibrillator shocks) occurred
      in 17/99 of patients with S-LV-D, in 15/201 with MM-LV-D, and in only 1/118 of
      those with normal LV-EF. After adjustment for age, an extent of LGE >11.3%, a
      dilated LV (male >112ml/m2; female >92ml/m2) and a WMSI>1.59 were associated with
      adverse cardiac events in patients with MM-LV-D. In patients with MM-LV-D, when
      each of these 3 factors was observed, the prognosis was worse respect to those
      with 1-2 factors and no factor (p=0.035 and p=0.004, respectively). Prognosis was
      similar (p=0.61) between MM-LV-D patients with all 3 factors and those with S-LV
      dysfunction. CONCLUSIONS: A multiparametric CMR approach, which includes LGE,
      dilated LV and WMSI, permits to identify post MI patients with MM-LV-D with a
      risk of cardiac events similar to those with S-LV-D. Further multicenter studies
      are needed to confirm our data.

PMID- 28757090
TI  - Association between gamma-glutamyltransferase level and incidence of atrial
      fibrillation: A nationwide population-based study.
AB  - BACKGROUND: Information on the association between gamma-glutamyltransferase
      (GGT) and the incidence of atrial fibrillation (AF) is scarce. We evaluated the
      association between GGT and AF incidence, and the interaction between GGT and
      obesity on developing AF in a large population-based cohort. METHODS: We
      evaluated 266,550 individuals (mean age, 53+/-11; men, 48.4%) who underwent the
      national insurance health checkup between 2004 and 2008. Subjects were
      categorized in accordance with quartiles of GGT levels (range: Q1, 0-15U/L; Q2,
      16-22U/L; Q3, 23-38U/L; Q4, >=39U/L). The association between GGT levels and AF
      incidence was analyzed by using multivariable Cox proportional-hazards regression
      models. RESULTS: During a median of 8years' follow-up, 5034 individuals (1.9%)
      were newly diagnosed with AF. The crude AF incidence gradually increased with
      increases in GGT level (1.9, 2.5, 2.8, and 3.1 per 1000 person-years in the Q1,
      Q2, Q3, and Q4 GGT groups, respectively; p for trend <0.001). In the
      multivariable Cox proportional hazard models, GGT level showed a dose-response
      relationship with AF incidence. The subjects with the highest quartile of GGT
      levels had a significantly higher risk of AF (hazard ratio [HR], 1.31; 95%
      confidence interval [CI], 1.18-1.45; p<0.001). When the analysis was stratified
      by body mass index (BMI), GGT level showed good discrimination for AF incidence
      only in the non-obese population (BMI<25kg/m2), and not in the obese population
      (BMI>=25kg/m2; p interaction<0.001). CONCLUSIONS: In this large population-based
      study, elevated GGT level showed a significant association with increased risk of
      AF, especially in a non-obese population.

PMID- 28757091
TI  - Advances in methods for characterization of hepatic urea cycle enzymatic activity
      in HepaRG cells using UPLC-MS/MS.
AB  - Current methodologies for the assessment of urea cycle (UC) enzymatic activity
      are insufficient to accurately evaluate this pathway in biological specimens
      where lower UC is expected. Liver cell lines, including HepaRG, have been
      described to have limited nitrogen fixation through the UC, limiting their
      applicability as biocomponents for Bioartificial Livers (BAL). This work aims to
      develop novel and sensitive analytical solutions using Mass Spectrometry-based
      methodology to measure the activity of four UC enzymes in human liver and HepaRG
      cells. Activity of carbamoyl-phosphate synthetase I (CPS I), ornithine
      transcarbamylase (OTC), argininosuccinate lyase (ASL) and arginase (ARG I and II)
      was determined on homogenates from normal human liver and HepaRG cells cultured
      in monolayer or in the AMC-BAL. Enzyme products were determined by stable-isotope
      dilution UPLC-MS/MS. Activity of CPS I, OTC and ARG I/II enzymes in HepaRG
      monolayer cultures was considerably lower than in human control livers albeit an
      increase was achieved in HepaRG-BAL cultures. Improved analytical assays
      developed for the study of UC enzyme activity, contributed to gain understanding
      of UC function in the HepaRG cell line. The decreased activity of CPS I suggests
      that it may be a potential rate-limiting factor underlying the low UC activity in
      this cell line.

PMID- 28757092
TI  - Beta-hairpin hydrogels as scaffolds for high-throughput drug discovery in three
      dimensional cell culture.
AB  - Automated cell-based high-throughput screening (HTS) is a powerful tool in drug
      discovery, and it is increasingly being recognized that three-dimensional (3D)
      models, which more closely mimic in vivo-like conditions, are desirable screening
      platforms. One limitation hampering the development of 3D HTS is the lack of
      suitable 3D culture scaffolds that can readily be incorporated into existing HTS
      infrastructure. We now show that beta-hairpin peptide hydrogels can serve as a 3D
      cell culture platform that is compatible with HTS. MAX8 beta-hairpin peptides can
      physically assemble into a hydrogel with defined porosity, permeability and
      mechanical stability with encapsulated cells. Most importantly, the hydrogels can
      then be injected under shear-flow and immediately reheal into a hydrogel with the
      same properties exhibited prior to injection. The post-injection hydrogels are
      cell culture compatible at physiological conditions. Using standard HTS equipment
      and medulloblastoma pediatric brain tumor cells as a model system, we show that
      automatic distribution of cell-peptide mixtures into 384-well assay plates
      results in evenly dispensed, viable MAX8-cell constructs suitable for
      commercially available cell viability assays. Since MAX8 peptides can be
      functionalized to mimic the microenvironment of cells from a variety of origins,
      MAX8 peptide gels should have broad applicability for 3D HTS drug discovery.

PMID- 28757093
TI  - Biochemical characterization of Arabidopsis thaliana starch branching enzyme 2.2
      reveals an enzymatic positive cooperativity.
AB  - Starch Branching Enzymes (SBE) catalyze the formation of alpha(1 -> 6) branching
      points on starch polymers: amylopectin and amylose. SBEs are classified in two
      groups named type 1 and 2. Both types are present in the entire plant kingdom
      except in some species such as Arabidopsis thaliana that expresses two type 2
      SBEs: BE2.1 and BE2.2. The present work describes in vitro enzymatic
      characterization of the recombinant BE2.2. The function of recombinant BE2.2 was
      characterized in vitro using spectrophotometry assay, native PAGE and HPAEC-PAD
      analysis. Size Exclusion Chromatography separation and SAXS experiments were used
      to identify the oligomeric state and for structural analysis of this enzyme.
      Optimal pH and temperature for BE2.2 activity were determined to be pH 7 and 25 
      degrees C. A glucosyl donor of at least 12 residues is required for BE2.2
      activity. The reaction results in the transfer in an alpha(1 -> 6) position of a
      glucan preferentially composed of 6 glucosyl units. In addition, BE2.2, which has
      been shown to be monomeric in absence of substrate, is able to adopt different
      active forms in presence of branched substrates, which affect the kinetic
      parameters. BE2.2 has substrate specificity similar to those of the other type-2
      BEs. We propose that the different conformations of the enzyme displaying more or
      less affinity toward its substrates would explain the adjustment of the kinetic
      data to the Hill equation. This work describes the enzymatic parameters of
      Arabidopsis BE2.2. It reveals for the first time conformational changes for a
      branching enzyme, leading to a positive cooperative binding process of this
      enzyme.

PMID- 28757094
TI  - DDM at Work: Reply to comments on "Dependency distance: A new perspective on
      syntactic patterns in natural languages".
AB  - We provide responses to the commentaries in this volume to evaluate, clarify and
      extend some of the arguments in Dependency distance: A new perspective on
      syntactic patterns in natural languages. Evidences show that DDM (dependency
      distance minimization) is an important linguistic universal, biologically or
      cognitively motivated, in shaping the language system. As a general tendency, DDM
      works quite well in theoretical argumentations as well as practical applications.
      However, this does not mean that DDM is the only linguistic universal that works:
      it is highly possible that other factors, which might be biologically,
      physically, socially or culturally motivated, work as well to jointly mold
      languages.

PMID- 28757095
TI  - A novel type 1/2 hybrid IncC plasmid carrying fifteen antimicrobial resistance
      genes recovered from Proteus mirabilis in China.
AB  - IncC plasmids are of great concern as vehicles of broad-spectrum cephalosporins
      and carbapenems resistance genes blaCMY and blaNDM. The aim of this study was to
      sequence and characterize a multidrug resistance (MDR) IncC plasmid (pPm14C18)
      recovered from Proteus mirabilis. pPm14C18 was identified in a CMY-2-producing P.
      mirabilis isolate from chicken in China in 2014, and could be transferred to
      Escherichia coli conferring an MDR phenotype. Whole genome sequencing confirmed
      pPm14C18 was a novel type 1/2 hybrid IncC plasmid 165,992bp in size, containing
      fifteen antimicrobial resistance genes. It harboured a novel MDR mosaic region
      comprised of a hybrid Tn21tnp-pDUmer, in which blaCTX-M-65, dfrA32 and ereA were
      firstly reported in IncC plasmid. Phylogenetic relationship reconstruction based
      on the nucleotide sequences of the 52 IncC backbones showed all type 1 IncC
      plasmids were clustered into one clade, and then merged with pPm14C18 and finally
      with the type 2 IncC plasmids and another type 1/2 hybrid IncC plasmid pYR1. The
      MDR IncC plasmids in P. mirabilis of animal origin might threaten public health,
      which should be drawn more attention.

PMID- 28757097
TI  - Nursing role on rapid recovery programmes fast-track.
AB  - Rapid recovery (RR) or fast-track programmes are aimed at reducing surgical
      stress, leading to a reduction in nurse workload, costs and hospital stay,
      greater patient empowerment, early post-surgical recovery and reduced morbidity
      and mortality. These new protocols require the coordinated participation of a
      multidisciplinary team. Based on an integrative review of the literature, this
      paper aims to define the concept of a RR or fast track programme and show the
      existing evidence on the implementation of these programmes in nursing. The
      benefits and low incidence of damage of RR programmes in nursing justify their
      implementation. The programmes require greater support and diffusion in order to
      develop, as well as more research to increase the evidence on the effectiveness
      and efficiency of the protocols.

PMID- 28757098
TI  - Draft genome sequence of Exiguobacterium aurantiacum strain PN47 isolate from
      saline ponds, known as "Salar del Huasco", located in the Altiplano in the North
      of Chile.
AB  - In this report, we present a draft genome of 2,886,173bp of an Exiguobacterium
      aurantiacum strain PN47 isolate from the sediment of a saline pond named "Salar
      del Huasco" in the Altiplano in the North of Chile. Strain PN47 encodes adaptive
      characteristics enabling survival in extreme environmental conditions of high
      heavy metal and salt concentrations and high alkalinity.

PMID- 28757099
TI  - Gonadotropin inhibitory hormone and RF9 stimulate hypothalamic-pituitary-adrenal
      axis in adult male rhesus monkeys.
AB  - Stress activates gonadotropin inhibitory hormone (GnIH), hypothalamic-pituitary
      adrenal axis (HPA-axis) and represses hypothalamic-pituitary-gonadal axis (HPG
      axis) but RF9 administration relieves stress-induced repression of the HPG-axis.
      Importantly, it was not known whether GnIH signaling and RF9 synthetic peptide
      modulate the HPA axis. To assess this, mammalian orthologs of GnIH (RFRP-1 and
      RFRP-3) and RF9 were administered to intact adult male rhesus monkeys. RFRP-1
      (125MUg/animal), RFRP-3 (250MUg/animal) and RF9 (0.1mg/kg BW) were intravenously
      (iv) injected into normal fed (n=4) monkeys. Additionally, a single bolus iv
      injection of RF9 (0.1mg/kg BW) was also administered to 48h fasted monkeys (n=4)
      to check the effects of RF9 signaling on an activated HPA-axis. Serial blood
      samples were collected, centrifuged and the obtained plasma was used for the
      analysis of cortisol by specific enzyme immunoassay. RFRP-1 treatment
      significantly increased cortisol levels while RFRP-3 increased the plasma
      cortisol, but the effect was non-significant. RF9 treatment significantly
      increased cortisol levels in normal fed animals. In contrast, RF9 injection did
      not significantly alter circulating cortisol in fasted monkeys. In conclusion,
      our results suggest stimulatory action of RFRPs and RF9 on the HPA axis in the
      adult male monkeys. However, the mechanism and site of action of RFRP-1 and RF9
      along the HPA-axis is still unknown. Therefore, further studies are needed to
      decipher the mechanism and site of action of RFRPs and RF9 on the HPA axis in
      primates.

PMID- 28757096
TI  - Clinical effects of chemical exposures on mitochondrial function.
AB  - Mitochondria are critical for the provision of ATP for cellular energy
      requirements. Tissue and organ functions are dependent on adequate ATP
      production, especially when energy demand is high. Mitochondria also play a role
      in a vast array of important biochemical pathways including apoptosis, generation
      and detoxification of reactive oxygen species, intracellular calcium regulation,
      steroid hormone and heme synthesis, and lipid metabolism. The complexity of
      mitochondrial structure and function facilitates its diverse roles but also
      enhances its vulnerability. Primary disorders of mitochondrial bioenergetics, or
      Primary Mitochondrial Diseases (PMD) are due to inherited genetic defects in the
      nuclear or mitochondrial genomes that result in defective oxidative
      phosphorylation capacity and cellular energy production. Secondary mitochondrial
      dysfunction is observed in a wide range of diseases such as Alzheimer's and
      Parkinson's disease. Several lines of evidence suggest that environmental
      exposures cause substantial mitochondrial dysfunction. Whereby literature from
      experimental and human studies on exposures associated with Alzheimer's and
      Parkinson's diseases exist, the significance of exposures as potential triggers
      in Primary Mitochondrial Disease (PMD) is an emerging clinical question that has
      not been systematically studied.

PMID- 28757100
TI  - Design, synthesis and bioactivities of Celecoxib analogues or derivatives.
AB  - A series of Celecoxib analogues or derivatives were designed and synthesized, and
      their biological activities were studied. The results of inhibitory activity in
      vitro proved that compounds 1a, 1h, 1i, 1l and 1p had better inhibitory effect on
      COX-2, and the selectivity was higher. Among them, the inhibitory activity of
      compound 1h to COX-2 was IC50=0.049MUmol/L and SI >1000. Moreover, the
      experimental results of anti-inflammatory activity in vivo showed that they had
      good anti-inflammatory activity and could inhibit the release of PGE-2.
      Therefore, these compounds have better druggability.

PMID- 28757101
TI  - Discovery of a tetrahydroisoquinoline-based HDAC inhibitor with improved plasma
      stability.
AB  - Histone deacetylase inhibitors with desirable pharmacokinetic profiles which can
      be delivered to solid tumor tissues in large amount might be promising to treat
      solid tumor effectively. Herein, structural modification of a previously reported
      tetrahydroisoquinoline-based HDAC inhibitor 1 was carried out to improve its
      plasma stability for more feasible drug delivery. Among three newly synthesized
      analogs, the in vitro rat plasma stability of compound 2 (t1/2=630min) was over 5
      fold improved than its parent 1 (t1/2=103min). In vitro activity evaluation
      showed that compound 2 and 1 exhibited similar HDACs inhibitory activity, which
      was validated by western blot analysis and antiproliferative assay. Moreover,
      compared with 1, compound 2 exhibited comparable, if not higher, in vivo
      antitumor activity in a human breast carcinoma (MDA-MB-231) xenograft model.

PMID- 28757102
TI  - New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and
      antiviral activity.
AB  - New 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidine (PMEO-DAPy) and 1-[2
      (phosphonomethoxy)ethyl]-5-azacytosine (PME-5-azaC) prodrugs were prepared with a
      pro-moiety consisting of carbonyloxymethyl esters (POM, POC), alkoxyalkyl esters,
      amino acid phosphoramidates and/or tyrosine. The activity of the prodrugs was
      evaluated in vitro against different virus families. None of the synthesized
      prodrugs demonstrated activity against RNA viruses but some of them proved active
      against herpesviruses [including herpes simplex virus (HSV), varicella-zoster
      virus (VZV), and human cytomegalovirus (HCMV)]. The bis(POC) and the bis(amino
      acid) phosphoramidate prodrugs of PMEO-DAPy inhibited herpesvirus replication at
      lower doses than the parent compound although the selectivity against HSV and VZV
      was only slightly improved compared to PMEO-DAPy. The mono-octadecyl ester of PME
      5-azaC emerged as the most potent and selective PME-5-azaC prodrug against HSV,
      VZV and HCMV with EC50's of 0.15-1.12uM while PME-5-azaC only had marginal anti
      herpesvirus activity. Although the bis(hexadecylamido-l-tyrosyl) and the bis(POM)
      esters of PME-5-azaC were also very potent anti-herpesvirus drugs, these were
      less selective than the mono-octadecyl ester prodrug.

PMID- 28757103
TI  - [P. Merviel in response to the article of G. Chene et al. "How I
      do...laparoscopic removal of Essure(r) device?"]

PMID- 28757104
TI  - [What haemostatic technique should we use for opportunistic salpingectomy during
      benign laparoscopic hysterectomy?]
AB  - OBJECTIVE: To compare ovarian function before and after laparoscopic hysterectomy
      with bilateral salpingectomy for benign lesions with two different systems of
      haemostasis. METHODS: In this prospective randomized study comparing two types of
      energy used for coagulation in bilateral salpingectomy (group A: bipolar electric
      energy, versus group B: ultrasonic advanced energy [Harmonic(r)]), forty
      consecutive non-menopausal patients undergoing laparoscopic hysterectomy for
      benign lesions were included. Values of anti-Mullerian hormone (AMH), LH and FSH,
      antral follicle count (AFC) and ovarian vascularization on bilateral Doppler
      ultrasound, quality of life (questionnaire) were assessed preoperatively and at 1
      and 3 months postoperatively. RESULTS: Preliminary analysis showed shorter
      salpingectomy operating time (P<0.0001) and less bleeding (P<0.005) in group B.
      In group A, there was no statistical difference except a decrease in AFC at 1 and
      3 months on the right ovary (P=0.04). In group B, AMH levels were significantly
      lower postoperatively at 3 months and LH levels were increased at 3 months
      (respectively P=0.02 et P=0.04). There was no statistical difference in the
      ultrasonographic data. Quality of life did not significantly differ in both
      groups. CONCLUSION: Preliminary findings showed reduced AMH levels at 3months
      postoperatively in ultrasonic energy group whereas there was no significative
      menopausal symptoms. It seems important to continue this study in order to know
      the real effects of both energy systems on the ovarian function.

PMID- 28757105
TI  - [Double-balloon catheter compared to vaginal dinoprostone for cervical ripening
      in obese women at term].
AB  - OBJECTIVE: To compare the efficacy of a double-balloon catheter versus vaginal
      prostaglandin E2 (dinoprostone) for cervical ripening in obese patients with
      unfavorable cervix at term. METHODS: The study had an open-label, prospective
      combined with retrospective, observational design. From January 2013 until May
      2016, a prospective cohort study of 46 women with pre-pregnancy BMI>30kg/m2, live
      singleton term fetuses (>37 weeks) in vertex presentation and unfavorable cervix
      (Bishop score<6), who underwent labor induction for conventional indications
      using a double-balloon catheter. In the same period, 46 obese women who had
      undergone cervical ripening using vaginal dinoprostone (3mg) were retrospectively
      included. Women in groups were paired according to Bishop score before the
      insertion, pre-pregnancy BMI and parity. The primary outcome was a favorable
      cervix (Bishop score >=6) 24h after cervical ripening. RESULTS: After 24h, there
      was a significantly higher rate of women with favorable cervix (Bishop score >=6)
      in the double-balloon group than in dinoprostone group (80.4% vs 47.8%; P=0.001).
      After adjustment, a double-balloon catheter was significantly associated with an
      efficient cervical ripening compared to vaginal dinoprostone (aOR 7.81, 95% CI
      2.58-23.60). No difference was observed in cesarean section rate (39.1% in each
      group; P=0.96) and in mean induction time to vaginal delivery (34.5h in the
      balloon group vs 36.5h in the dinoprostone group; P=0.53). Maternal and neonatal
      outcomes were similar. CONCLUSION: For obese patients at term, cervical ripening
      using a double-balloon catheter is more efficient on Bishop score after 24h
      compared to vaginal dinoprostone.

PMID- 28757106
TI  - [Quality of oocytes and embryos from women with polycystic ovaries syndrome:
      State of the art].
AB  - The frequency of polycystic ovary syndrome (PCOS) and the consequent fertility
      disorders cause many difficulties in the management of the assisted reproductive
      technics. Some studies are focused on different additional treatments,
      stimulation protocols or techniques that could optimize the in vitro
      fertilization cycles. The quality of the oocytes and embryos of these patients is
      also an outstanding issue. They remain difficult to actually evaluate during
      management, and none of the few published studies on this subject demonstrated
      any inferiority, compared to control patients. However, many differences have
      been highlighted, studying intra- and extra-ovarian factors. The advent of new
      genetic techniques could allow a better understanding of the pathophysiological
      mechanisms of the syndrome, as well as refining the evaluation of oocytes and
      embryos, in order to better predict the results of in vitro fertilization
      attempts. Pregnancy and birth rates, however, appear to be comparable to those of
      the general population.

PMID- 28757107
TI  - [H. Madar and L. Sentilhes in response to J. Boujenah's correspondence on the
      article: For a targeted use of aspirin. Gynecol Obstet Fertil Senol 2017;45:224
      30].

PMID- 28757108
TI  - Celastrol synergizes with oral nifedipine to attenuate hypertension in
      preeclampsia: a randomized, placebo-controlled, and double blinded trial.
AB  - Preeclampsia, a disease mainly manifesting as serious hypertension during
      pregnancy, affects expectant mothers around the globe. Celastrol, a naturally
      existing triterpenoid, is known to exhibit beneficial effects attenuating
      cardiovascular symptoms including hypertension. We here assessed the treatment
      outcome against preeclampsia with a combined use of celastrol and nifedipine. A
      total of 626 patients with preeclampsia were enrolled, screened, and assigned by
      random to groups receiving either nifedipine + placebo or nifedipine + celastrol
      orally. Time required to control hypertension as well as time before another
      hypertensive crisis were defined as primary end points. Secondary end points
      include the number of dosages required to control hypertension, as well as
      maternal and neonatal adverse effects. The time to control hypertension showed a
      marked reduction in nifedipine + celastrol group, while time before a new
      hypertensive crisis was significantly lengthened with the treatment, compared
      with the nifedipine + placebo group. The number of dosages required to control
      hypertension was also lower in the nifedipine + celastrol group. The two
      treatment groups were not statistically different regarding adverse effects,
      either maternal or neonatal. Results from the current study provide evidence for
      the potential role of celastrol serving as an effective and safe adjuvant to oral
      nifedipine against hypertension in patients with preeclampsia.

PMID- 28757109
TI  - The effect of empagliflozin on muscle sympathetic nerve activity in patients with
      type II diabetes mellitus.
AB  - Inhibition of sodium glucose cotransporter 2 with empagliflozin results in
      caloric loss by increasing urinary glucose excretion and has a mild diuretic
      effect. Diuretic effects are usually associated with reflex-mediated increases in
      sympathetic tone, whereas caloric loss is associated with decreased sympathetic
      tone. In an open-label trial, muscle sympathetic nerve activity (MSNA) (burst
      frequency, burst incidence, and total MSNA) was assessed using microneurography
      performed off-treatment and on day 4 of treatment with empagliflozin 25 mg once
      daily in 22 metformin-treated patients with type II diabetes (mean [range] age 54
      [40-65] years). Systolic and diastolic blood pressure (BP), heart rate, urine
      volume, and body weight were assessed before and on day 4 (BP, heart rate), day 5
      (urine volume), or day 6 (body weight) of treatment with empagliflozin. After 4
      days of treatment with empagliflozin, no significant changes in MSNA were
      apparent despite a numerical increase in urine volume, numerical reductions in
      BP, and significant weight loss. There were no clinically relevant changes in
      heart rate. Empagliflozin is not associated with clinically relevant reflex
      mediated sympathetic activation in contrast to increases observed with diuretics
      in other studies. Our study suggests a novel mechanism through which sodium
      glucose cotransporter 2 inhibition affects human autonomic cardiovascular
      regulation.

PMID- 28757110
TI  - Quantitative EEG findings and response to treatment with antiepileptic
      medications in children with epilepsy.
AB  - BACKGROUND: Epilepsy is a common chronic disorder in pediatric neurology.
      Nowadays, a variety of antiepileptic drugs (AEDs) are available. A scientific
      method designed to evaluate the effectiveness of AEDs in the early stage of
      treatment has not been reported. PURPOSE: In this study, we try to use
      quantitative EEG (QEEG) analysis as a biomarker to evaluate therapeutic
      effectiveness. METHODS: 20 epileptic children were enrolled in this study.
      Participants were classified as effective if they achieved a reduction in seizure
      frequency over 50%. Ineffective was defined as a reduction in seizure frequency
      less than 50%. Eleven participants were placed in the effective group, the
      remaining 9 participants were placed in the ineffective group. EEG segments
      before and after 1-3months of antiepileptic drugs start/change were analyzed and
      compared by QEEG analysis. The follow-up EEG segments after the 2nd examinations
      were used to test the accuracy of the analytic results. RESULTS: Six crucial EEG
      feature descriptors were selected for classifying the effective and ineffective
      groups. Significantly increased RelPowAlpha_avg_AVG, RelPowAlpha_snr_AVG,
      HjorthM_avg_AVG, and DecorrTime_snr_AVG values were found in the effective group
      as compared to the ineffective group. On the contrary, there were significantly
      decreases in DecorrTime_std_AVG, and Wavelet_db4_EnergyBand_5_avg_AVG values in
      the effective group as compared to the ineffective group. The analyses yielded a
      precision rate of 100%. When the follow-up EEG segments were used to test the
      analytic results, the accuracy was 83.3%. CONCLUSION: The developed method is a
      useful tool in analyzing the effectiveness of antiepileptic drugs. This method
      may assist pediatric neurologists in evaluating the efficacy of AEDs and making
      antiepileptic drug adjustments when managing epileptic patients in the early
      stage.

PMID- 28757111
TI  - Organ specific gene expression in the regenerating tail of Macrostomum lignano.
AB  - Temporal and spatial characterization of gene expression is a prerequisite for
      the understanding of cell-, tissue-, and organ-differentiation. In a multifaceted
      approach to investigate gene expression in the tail plate of the free-living
      marine flatworm Macrostomum lignano, we performed a posterior-region-specific in
      situ hybridization screen, RNA sequencing (RNA-seq) of regenerating animals, and
      functional analyses of selected tail-specific genes. The in situ screen revealed
      transcripts expressed in the antrum, cement glands, adhesive organs, prostate
      glands, rhabdite glands, and other tissues. Next we used RNA-seq to characterize
      temporal expression in the regenerating tail plate revealing a time restricted
      onset of both adhesive organs and copulatory apparatus regeneration. In addition,
      we identified three novel previously unannotated genes solely expressed in the
      regenerating stylet. RNA interference showed that these genes are required for
      the formation of not only the stylet but the whole male copulatory apparatus.
      RNAi treated animals lacked the stylet, vesicula granulorum, seminal vesicle,
      false seminal vesicle, and prostate glands, while the other tissues of the tail
      plate, such as adhesive organs regenerated normally. In summary, our findings
      provide a large resource of expression data during homeostasis and regeneration
      of the morphologically complex tail regeneration and pave the way for a better
      understanding of organogenesis in M. lignano.

PMID- 28757113
TI  - Cardiovascular risk and the effect of nitric oxide synthase inhibition in female
      rats: The role of estrogen.
AB  - It is known that autonomic modulation is responsive to ovarian hormone levels and
      that estrogen increases nitric oxide (NO) bioavailability. However, little is
      known about the interaction of nitric oxide synthase (NOS) isoforms with
      autonomic modulation, oxidative stress and cardiovascular risk in females. This
      study aimed to investigate cardiovascular, autonomic and oxidative parameters
      after selective NOS inhibition. A spectral analysis of systolic arterial pressure
      (SAP) and heart rate variability (HRV) was performed. NO levels, total
      antioxidant capacity (TRAP), lipid hydroperoxides (LOOH) and paraoxonase 1 (PON1)
      activity were measured in the plasma of rats treated with L-NG-nitroarginine
      methyl ester (L-NAME), S-methylisothiourea (SMT) or saline. Wistar rats,
      ovariectomized (OVX) with or without estradiol treatment (1mg/kg/day) or with a
      false ovariectomy (SHAM), were submitted to artery and vein catheterization.
      Cardiovascular parameters were evaluated before and after the administration of
      saline or NOS inhibitors. After 2h, plasma samples were collected for biochemical
      measurement. At baseline, cardiovascular and autonomic parameters were not
      different among the groups. L-NAME, the constitutive NOS isoform (cNOS)
      inhibitor, promoted an increase in mean arterial pressure (MAP) and a reduction
      in the low frequency band (LF) of SAP of SHAM rats, but this increase was smaller
      in OVX animals, which also showed a reduction in PON1 activity. The decreased
      activity of PON1 caused by L-NAME was prevented in the OVX+E group. SMT, an
      inducible NOS isoform (iNOS) inhibitor, promoted an increase in MAP and in the LF
      of SAP, in interbeat interval (IBI) parameters at LFnu and in LF/HF ratio of HRV
      in all groups, but the OVX+E had lower levels of NO when compared with the OVX
      group. Our data suggest that while cNOS contributes to maintaining the activity
      of PON1 in OVX rats, iNOS activity maintains the levels of NO in OVX+E rats.

PMID- 28757112
TI  - The abrogation of condensin function provides independent evidence for defining
      the self-renewing population of pluripotent stem cells.
AB  - Heterogeneity of planarian stem cells has been categorised on the basis of single
      cell expression analyses and subsequent experiments to demonstrate lineage
      relationships. Some data suggest that despite heterogeneity in gene expression
      amongst cells in the cell cycle, in fact only one sub-population, known as sigma
      neoblasts, can self-renew. Without the tools to perform live in vivo lineage
      analysis, we instead took an alternative approach to provide independent evidence
      for defining the self-renewing stem cell population. We exploited the role of
      highly conserved condensin family genes to functionally assay neoblast self
      renewal properties. Condensins are involved in forming properly condensed
      chromosomes to allow cell division to proceed during mitosis, and their
      abrogation inhibits mitosis and can lead to repeated endoreplication of the
      genome in cells that make repeated attempts to divide. We find that planarians
      possess only the condensin I complex, and that this is required for normal stem
      cell function. Abrogation of condensin function led to rapid stem cell depletion
      accompanied by the appearance of 'giant' cells with increased DNA content. Using
      previously discovered markers of heterogeneity we show that enlarged cells are
      always from the sigma-class of the neoblast population and we never observe
      evidence for endoreplication for the other neoblast subclasses. Overall, our data
      establish that condensins are essential for stem cell maintenance and provide
      independent evidence that only sigma-neoblasts are capable of multiple rounds of
      cell division and hence self-renewal.

PMID- 28757115
TI  - There is no defence for 'Conscientious objection' in reproductive health care.
AB  - A widespread assumption has taken hold in the field of medicine that we must
      allow health care professionals the right to refuse treatment under the guise of
      'conscientious objection' (CO), in particular for women seeking abortions. At the
      same time, it is widely recognized that the refusal to treat creates harm and
      barriers for patients receiving reproductive health care. In response, many
      recommendations have been put forward as solutions to limit those harms. Further,
      some researchers make a distinction between true CO and 'obstructionist CO',
      based on the motivations or actions of various objectors. This paper argues that
      'CO' in reproductive health care should not be considered a right, but an
      unethical refusal to treat. Supporters of CO have no real defence of their
      stance, other than the mistaken assumption that CO in reproductive health care is
      the same as CO in the military, when the two have nothing in common (for example,
      objecting doctors are rarely disciplined, while the patient pays the price).
      Refusals to treat are based on non-verifiable personal beliefs, usually religious
      beliefs, but introducing religion into medicine undermines best practices that
      depend on scientific evidence and medical ethics. CO therefore represents an
      abandonment of professional obligations to patients. Countries should strive to
      reduce the number of objectors in reproductive health care as much as possible
      until CO can feasibly be prohibited. Several Scandinavian countries already have
      a successful ban on CO.

PMID- 28757114
TI  - Sex differences in age-related changes in the sleep-wake cycle.
AB  - Age-related changes in sleep and circadian regulation occur as early as the
      middle years of life. Research also suggests that sleep and circadian rhythms are
      regulated differently between women and men. However, does sleep and circadian
      rhythms regulation age similarly in men and women? In this review, we present the
      mechanisms underlying age-related differences in sleep and the current state of
      knowledge on how they interact with sex. We also address how testosterone,
      estrogens, and progesterone fluctuations across adulthood interact with sleep and
      circadian regulation. Finally, we will propose research avenues to unravel the
      mechanisms underlying sex differences in age-related effects on sleep.

PMID- 28757116
TI  - Deep Sedation With Propofol Administered by Electrophysiologists in Atrial
      Fibrillation Ablation.

PMID- 28757117
TI  - [Caracterization of HLA allo-immunization and clinical impact in transfusion and
      organ transplantation].
AB  - Allo-immunizations against HLA antigens are known to be deleterious in
      transfusion and organ transplantation. The development of new tests based on
      solid phase assays for screening and identification of HLA antibodies in
      particular those using Luminex(r) bead based technology has completely changed
      the way of allo-immunization monitoring because of their extreme sensitivity.
      They allow a better characterization of these antibodies, identification of
      acceptable antigens and the use of virtual cross-matches. All these new
      possibilities improve the managing of patients before and after platelets
      transfusion or organ transplantation. However, this technology displays some
      limits that should be known in order to interpret correctly the results. Beside
      these bead based assays, cellular cross-matches based on Complement Dependent
      Cytotoxicity (CDC) and flow cytometry are still used and useful in organ
      transplantation since beads are produced in vitro and do not reflected exactly
      what happens physiologically. Moreover, differences of sensitivity between these
      methods make results interpretation and decision making difficult in some cases.

PMID- 28757118
TI  - Experience With Prophylactic Gentamicin During Penile Prosthesis Surgery: A
      Retrospective Comparison of Two Different Doses.
AB  - BACKGROUND: Gentamicin has been determined to be active against a wide range of
      bacterial infections and has been commonly used as a preoperative antibiotic for
      inflatable penile prosthesis (IPP) implantation. However, the best dosing regimen
      to produce the safest optimal prophylactic effect remains to be determined. AIM:
      To compare low- and high-dose gentamicin as prophylaxis during IPP implantation.
      METHODS: We retrospectively analyzed two groups of patients who underwent IPP
      placement from April 14, 2012 through April 13, 2016. Group 1 was composed of 490
      patients who underwent IPP placement from April 14, 2012 through April 13, 2014
      and received a low dose of preoperative gentamicin at 80 mg every 8 hours for 1
      day. Group 2 was composed of 407 patients who underwent IPP placement from April
      14, 2014 through April 13, 2016 and received a single high dose of preoperative
      gentamicin at 5 mg/kg. We compared the infection rates of IPP and any gentamicin
      related toxicities. The same surgeon performed all procedures. All patients
      received additional vancomycin 1 g before incision and at 12 hours
      postoperatively. OUTCOME: Demographic data and IPP infection rate were compared
      and potential toxicities from the higher dose of gentamicin were closely
      monitored. RESULTS: There were no significant differences in mean age, mean body
      mass index, and mean interval for IPP placement and IPP infection between the two
      groups. No toxicity was seen with the higher gentamicin dose. Six cases in group
      1 (five de novo cases and one redo case, infection rate = 1.22%) and three cases
      in group 2 (two de novo cases and one redo case, infection rate = 0.74%) were
      found to have IPP infection. The infection rate in group 2 appeared to be lower
      than that in group 1, although a significant statistical difference was not
      achieved (P = .057). CLINICAL IMPLICATIONS: These findings would help guide
      urologists in choosing an optimal preoperative gentamicin dose for IPP surgery.
      STRENGTHS AND LIMITATIONS: This is the first study to report on the usage of high
      dose preoperative gentamicin for IPP surgery but with limitations as a
      retrospective study. CONCLUSIONS: Although not achieving a statistical
      difference, there was a trend for patients receiving a higher dose of
      preoperative gentamicin to have a lower IPP infection rate. No toxicity was
      encountered from the 5-mg/kg gentamicin dose. We recommend following prophylactic
      high-dose gentamicin guidelines. Xie D, Gheiler V, Lopez I, et al. Experience
      With Prophylactic Gentamicin During Penile Prosthesis Surgery: A Retrospective
      Comparison of Two Different Doses. J Sex Med 2017;14:1160-1164.

PMID- 28757120
TI  - Reply by Authors.

PMID- 28757121
TI  - Editorial Comment.

PMID- 28757119
TI  - Low Plasma Testosterone Is Associated With Elevated Cardiovascular Disease
      Biomarkers.
AB  - BACKGROUND: The relation between testosterone (T) plasma concentration and
      cardiovascular (CV) risk is unclear, with evidence supporting increased risk in
      men with low and high T levels. Few studies have assessed CV risk as a function
      of plasma T levels using objective biomarkers. AIM: To determine the relation
      between T levels and high-sensitivity CV risk biomarkers. METHODS: Ten thousand
      forty-one male patients were identified in the database of a commercial clinical
      laboratory performing biomarker testing. Patients were grouped by total T
      concentration and associations with the following biomarkers were determined:
      cardiac troponin I (cTnI), endothelin-1 (ET-1), interleukin-6 (IL-6), tumor
      necrosis factor-alpha (TNF-alpha), interleukin-17A, N-terminal pro-B-type
      natriuretic peptide (NTproBNP), high-density lipoprotein (HDL) cholesterol, high
      sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), and leptin.
      OUTCOMES: Association of CV risk markers with levels of T in men. RESULTS: The
      median age of the cohort was 58 years (interquartile range = 48-68), and the
      median plasma T level was 420 ng/dL (interquartile range = 304-565); T levels did
      not vary with patient age. An inverse relation between plasma T levels and CV
      risk was observed for 9 of 10 CV markers: cTnI, ET-1, IL-6, TNF-alpha, NTproBNP,
      HDL cholesterol, hs-CRP, HbA1c, and leptin. Even after adjusting for age, body
      mass index, HbA1c, hs-CRP, and HDL cholesterol levels, the CV markers IL-6, ET-1,
      NTproBNP, and leptin were significantly associated with a T level lower than 250
      ng/dL. CLINICAL IMPLICATIONS: Men with low T levels could be at increased risk
      for increased CV disease as seen by increased CV risk markers. STRENGTH AND
      LIMITATIONS: This study was performed in a group of 10,041 men and is the first
      study to examine CV risk associated with circulating T levels using a large panel
      of 10 objective biomarkers. This study is limited by an absence of clinical data
      indicating whether men had pre-existing CV disease or other CV risk factors.
      CONCLUSION: Men with low plasma T levels exhibit increases in CV risk markers,
      consistent with a potential increased risk of CV disease. Pastuszak AW, Kohn TP,
      Estis J, Lipshultz LI. Low Plasma Testosterone Is Associated With Elevated
      Cardiovascular Disease Biomarkers. J Sex Med 2017;14:1095-1103.

PMID- 28757122
TI  - Editorial Comment.

PMID- 28757123
TI  - Molecular and biochemical characterisation and recognition by the immune host of
      the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) of the abomasal nematode
      parasite Teladorsagia circumcincta.
AB  - A 1023 bp full length cDNA encoding Teladorsagia circumcincta GAPDH (TeciGAPDH)
      was cloned, expressed in Escherichia coli and the recombinant protein purified
      and its kinetic properties determined. A phylogenetic tree was constructed using
      helminth GAPDH sequences. The predicted protein consisted of 341 amino acids and
      was present as a single band of about 38 kDa on SDS-PAGE. Multiple alignments of
      the protein sequence of TeciGAPDH with homologues from other helminths showed
      that the greatest similarity (93%) to the GAPDH of Haemonchus contortus and
      Dictyocaulus viviparus, 82-86% similarity to the other nematode sequences and 68
      71% similarity to cestode and trematode enzymes. Substrate binding sites and
      conserved regions were identified and were completely conserved in other
      homologues. At 25  degrees C, the optimum pH for TeciGAPDH activity was pH 8, the
      Vmax was 1052 +/- 23 nmol min-1 mg-1 protein and the apparent Km for the
      substrate glyceraldehyde-3-phosphate was 0.02 +/- 0.01 mM (both mean +/- SD, n =
      2). Antibodies in both serum and saliva from field-immune, but not nematode
      naive, sheep recognised recombinant TeciGAPDH in enzyme-linked immunosorbent
      assays. The recognition of the recombinant protein by antibodies generated by
      exposure of sheep to native GAPDH indicates similar antigenicity of the two
      proteins.

PMID- 28757125
TI  - Update on childhood and adult infectious tracheitis.
AB  - The trachea is a pivotal organ of the respiratory tract. Rather than a genuine
      anatomic border, it acts as a crossroad in all respiratory infectious processes.
      Even though not strictly limited to the trachea, infections such as
      laryngotracheitis and tracheobronchitis are frequently diagnosed in children, in
      particular during the winter season. Infectious tracheitis etiologies are diverse
      and the distinction between viral and bacterial origins, albeit difficult,
      remains relevant considering the substantial differences in terms of gravity and
      therapeutic management. This literature review summarizes the microbiological and
      clinical aspects of community-acquired and nosocomial tracheitis in adults and
      children, as well as the adequate diagnostic and therapeutic approaches. It also
      highlights the emergence of fungal tracheitis in immunocompromised patients, of
      ventilator-associated tracheitis in intensive care medicine, and beyond all that
      the potential short and long-term consequences of tracheitis.

PMID- 28757124
TI  - Functional mapping of the N-terminal arginine cluster and C-terminal acidic
      residues of Kir6.2 channel fused to a G protein-coupled receptor.
AB  - Ion channel-coupled receptors (ICCRs) are original man-made ligand-gated ion
      channels created by fusion of G protein-coupled receptors (GPCRs) to the inward
      rectifier potassium channel Kir6.2. GPCR conformational changes induced by ligand
      binding are transduced into electrical current by the ion channel. This
      functional coupling is closely related to the length of the linker region formed
      by the GPCR C-terminus (C-ter) and Kir6.2N-terminus (N-ter). Manipulating the
      GPCR C-ter length allows to finely tune the channel regulation, both in amplitude
      and sign (opening or closing Kir6.2). In this work, we demonstrate that the
      primary sequence of the channel N-terminal domain is an additional parameter for
      the functional coupling with GPCRs. As for all Kir channels, a cluster of basic
      residues is present in the N-terminal domain of Kir6.2 and is composed of 5
      arginines which are proximal to the GPCR C-ter in the fusion proteins. Using a
      functional mapping approach, we demonstrate the role of specific arginines (R27
      and R32) for the function of ICCRs, indicating that the position and not the
      cluster of positively-charged arginines is critical for the channel regulation by
      the GPCR. Following observations provided by molecular dynamics simulation, we
      explore the hypothesis of interaction of these arginines with acidic residues,
      and using site-directed mutagenesis, we identified aspartate D307 and glutamate
      E308 residues as critical for the function of ICCRs. These results demonstrate
      the critical role of the N-terminal and C-terminal charged residues of Kir6.2 for
      its allosteric regulation by the fused GPCR.

PMID- 28757127
TI  - Corrigendum to "Accounting for "land-grabbing" from a biocapacity viewpoint"
      [Sci. Total Environ. Vol. 539, 2016, Pages 551-559].

PMID- 28757126
TI  - Nuclear localization of metabolic enzymes in immunity and metastasis.
AB  - Metabolism is essential to all living organisms that provide cells with energy,
      regulators, building blocks, enzyme cofactors and signaling molecules, and is in
      tune with nutritional conditions and the function of cells to make the
      appropriate developmental decisions or maintain homeostasis. As a fundamental
      biological process, metabolism state affects the production of multiple
      metabolites and the activation of various enzymes that participate in regulating
      gene expression, cell apoptosis, cancer progression and immunoreactions. Previous
      studies generally focus on the function played by the metabolic enzymes in the
      cytoplasm and mitochondrion. In this review, we conclude the role of them in the
      nucleus and their implications for cancer progression, immunity and metastasis.

PMID- 28757129
TI  - Corrigendum to: A comparison of forest and agricultural shallow groundwater
      chemical status a century after land use change [Sci. Total Environ. 529 (2015)
      82-90].

PMID- 28757128
TI  - Corrigendum to "Spatiotemporal variations and factors affecting soil nitrogen in
      the purple hilly area of Southwest China during the 1980s and the 2010s" [Sci.
      Total environ. 547 (2016) 173-181].

PMID- 28757130
TI  - Historical overview on the morphological characterization of large granular
      lymphocytes/natural killer cells.
AB  - Natural Killer (NK) cells were discovered when research on T cells produced an
      unexplained background, or "natural" cytotoxicity in non-immunized mice. The
      previously unknown cells were thus named "natural" killer cells, or NK cells.
      They are roughly defined by a lack of the T cell marker CD3 and a presence of
      CD56 (or NCAM, neural cell adhesion molecule) and correspond to the large
      granular lymphocytes (LGLs). This article is focused to the description the
      morphological features of these cells and of the LGLs and to the fundamental
      contribution of the Italian scientist Carlo E. Grossi to the ultrastructural
      characterization of these cells.

PMID- 28757131
TI  - Oral Tranexamic Acid Reduces Transfusions in Total Knee Arthroplasty.
AB  - BACKGROUND: Tranexamic acid (TXA) reduces intraoperative blood loss and
      transfusions in patients undergoing total knee arthroplasty. Although numerous
      studies demonstrate the efficacy of intravenous and topical TXA in these
      patients, few demonstrate the effectiveness and appropriate dosing
      recommendations of oral formulations. METHODS: A retrospective cohort study was
      performed to evaluate differences in transfusion requirements in patients
      undergoing primary unilateral total knee arthroplasty with either no TXA (n =
      866), a single-dose of oral TXA (n = 157), or both preoperative and postoperative
      oral TXA (n = 1049). Secondary outcomes included postoperative hemoglobin drop,
      total units transfused, length of stay, drain output, and cell salvage volume.
      RESULTS: Transfusion rates decreased from 15.4% in the no-oral tranexamic acid
      (OTA) group to 9.6% in the single-dose OTA group (P < .001) and 7% in the 2-dose
      group (P < .001), with no difference in transfusion rates between the single- and
      2-dose groups (P = .390). In addition, postoperative hemoglobin drop was reduced
      from 4.2 g/dL in the no-OTA group to 3.5 g/dL in the single-dose group (P < .01)
      and to 3.4 g/dL in the 2-dose group (P < .01), without a difference between the
      single- and 2-dose groups (P = .233). CONCLUSION: OTA reduces transfusions, with
      greater ease of administration and improved cost-effectiveness relative to other
      forms of delivery.

PMID- 28757132
TI  - Side-effects associated with ketamine use in depression: a systematic review.
AB  - This is the first systematic review of the safety of ketamine in the treatment of
      depression after single and repeated doses. We searched MEDLINE, PubMed,
      PsycINFO, and Cochrane Databases and identified 288 articles, 60 of which met the
      inclusion criteria. After acute dosing, psychiatric, psychotomimetic,
      cardiovascular, neurological, and other side-effects were more frequently
      reported after ketamine treatment than after placebo in patients with
      depresssion. Our findings suggest a selective reporting bias with limited
      assessment of long-term use and safety and after repeated dosing, despite these
      being reported in other patient groups exposed to ketamine (eg, those with
      chronic pain) and in recreational users. We recommend large-scale clinical trials
      that include multiple doses of ketamine and long-term follow up to assess the
      safety of long-term regular use.

PMID- 28757133
TI  - Corrigendum to "Autophagy-linked FYVE containing protein WDFY3 interacts with
      TRAF6 and modulates RANKL-induced osteoclastogenesis" [J. Autoimmun. 73C (2016)
      73-84].

PMID- 28757134
TI  - Effects of combined inositol hexakisphosphate and inositol supplement on
      antioxidant activity and metabolic enzymes in the liver of streptozotocin-induced
      type 2 diabetic rats.
AB  - Diabetes mellitus is associated with elevated reactive oxygen species, lipid
      abnormalities, reduced antioxidant activity and organ damage. This study examines
      the effects of combined inositol hexakisphosphate (IP6) and inositol supplement
      on antioxidant levels and other biochemical parameters in the liver of type 2
      diabetic rats. Five groups of Sprague-Dawley rats were studied. Six rats were fed
      normal diet (non-diabetic control), while 24 rats were fed high-fat diet (HFD)
      for 4 weeks. Diabetes was induced in 18 of the rats fed HFD by intraperitoneal
      administration of streptozotocin. The diabetic rats were separated into three
      groups namely: combined IP6 and inositol, glibenclamide and diabetic control. The
      non-diabetic group fed high-fat diet was classified as a high-fat control group.
      For the final four weeks of the experiment, all rats were fed normal diet and
      given their respective treatment regimes. Hepatic antioxidant status, metabolic
      enzyme activity, lipid profile, peroxidative damage and liver histology, as well
      as, serum aminotransferase and alkaline phosphatase activities, and total
      bilirubin concentration were assessed. Treatment with combined IP6 and inositol
      supplement significantly increased liver reduced glutathione and high-density
      lipoprotein levels while liver triglyceride levels and serum alkaline phosphatase
      activity were significantly reduced by 27%, 50%, 38.5%, and 69.2% respectively
      compared to the diabetic control. Hepatic superoxide dismutase, catalase, glucose
      6-phosphate dehydrogenase activities were significantly upregulated by 55%, 26%
      and 53% respectively in the diabetic rats treated with combined IP6 and inositol
      compared to the diabetic control. Combined IP6 and inositol treatment resulted in
      the preservation of liver cell integrity and improved antioxidant status in type
      2 diabetic rats.

PMID- 28757135
TI  - Synergism between thioredoxin reductase inhibitor ethaselen and sodium selenite
      in inhibiting proliferation and inducing death of human non-small cell lung
      cancer cells.
AB  - New effective treatment for human non-small cell lung cancer (NSCLC) is needed.
      The thioredoxin (Trx) system composes of thioredoxin reductase (TrxR), Trx and
      NADPH. In this study, we combined an organic selenium compound--TrxR inhibitor
      ethaselen (BBSKE) with low dosage sodium selenite to inhibit proliferation and
      induce death of NSCLC cells, and identified underlying mechanisms. Synergistic
      anti-proliferation effect of BBSKE and selenite was found in human NSCLC cell
      lines, A549, NCI-H1299 and NCI-1266. A significant increase of apoptosis,
      necrosis and autophagy were observed in the group of BBSKE plus selenite in A549
      cells. The autophagy induced by BBSKE and selenite inhibited apoptosis and
      necrosis. In addition, BBSKE plus selenite induced G2/M arrest, which was
      verified by the alteration of gene and protein expression of cell cycle
      regulatory complexes. The intracellular enzyme activity of TrxR was remarkably
      decreased by cotreatment of BBSKE and selenite. Besides, the mRNA and protein
      level of TrxR1 and Trx1 were significantly inhibited by cotreatment of BBSKE and
      selenite. HEK 293 cells overexpressing TrxR1 were more sensitive to BBSKE plus
      selenite. The nuclear translocation of Trx1 and Ref-1, as well as expression of
      Ref-1 and AP-1 were inhibited by combination treatment. In short, BBSKE
      synergizes selenite in inhibiting proliferation and inducing death of NSCLC
      cells; BBSKE combined with selenite may be a treatment strategy for NSCLC.

PMID- 28757136
TI  - Iminoenamine based novel androgen receptor antagonist exhibited anti-prostate
      cancer activity in androgen independent prostate cancer cells through inhibition
      of AKT pathway.
AB  - Treatment by androgen receptor (AR) antagonists is one of the regimens for
      prostate cancer. The prolonged treatment with AR antagonist leads to the
      expression of point mutation in the ligand binding domain of the AR. This point
      mutation causes resistance to AR antagonist by converting them into an agonist.
      The T887A mutated AR was frequently expressed in androgen independent prostate
      cancer (AIPC) patients. Through literature survey and molecular modelling, we
      have identified a novel AR antagonist having a bulky beta-iminoenamine BF2
      complex scaffold. The tested and standard ligands were screened in AR positive
      (LNCaP, MCF-7 and MDA-MB-453), AR negative (PC3), and non-cancerous (3T3) cell
      lines through anti-proliferation assay. The ligand, ARA3 was the most potent
      molecule among all the tested ligands and was 7.6 folds selective for AR positive
      cell lines. The mechanism of anti-prostate cancer activity of ARA3 was confirmed
      by western blot, qPCR, and apoptotic assays in LNCaP (T887A positive AR) cells.
      Structural activity relationship was derived by correlating the in-vitro and in
      silico data. Consequently, we have identified the essential functional groups
      that could prevent the resistance concerning mutant AR. The ARA3 induces the
      apoptosis in AIPC cells by preventing the AR mediated activation of AKT pathway.
      The bicalutamide did not induce the apoptosis because it failed to prevent the AR
      mediated activation of AKT.

PMID- 28757137
TI  - In vitro and in vivo pharmacokinetics and toxicity evaluation of curcumin
      incorporated titanium dioxide nanoparticles for biomedical applications.
AB  - The present study deals with the preparation of stable Curcumin incorporated
      Titaniumdioxide Nanoparticles (CTNPs) by coprecipitation method for improving the
      bioavailability of curcumin and site specific drug delivery. The prepared
      nanoparticles were characterized by UV visible spectroscopy, FTIR, XRD, DLS, SEM
      and EDX. The characterization studies showed the interaction of curcumin to
      titanium dioxide nanoparticles. The average size of the prepared CTNPs was found
      to be ~29 nm with zetapotential of-53.790 mV. In vivo and in vitro toxicological
      evaluations were carried out to determine the biological effect of CTNPs. In
      vitro parameters like cell viability, Lactate dehydrogenase (LDH) Assay, Neutral
      red uptake (NRU) assay and uptake of curcumin from CTNPs by the cells had been
      investigated. In vitro toxicity studies in THP1 and H9c2 cell lines showed that
      CTNPs are safe even at a dose of 200 ng. The in vivo part of the study was
      carried out with different doses of Curcumin (1 mg-20 mg/kg body weight),
      Titaniumdioxide Nanoparticles (TNPs) (1 mg-5 mg/kg Body weight) and CTNPs (5 mg
      10 mg/kg Body weight) in Sprague dawley rat models to determine the
      pharmacokinetics and genotoxicity of the nanoparticle. This was done by analysing
      the parameters like SGPT, SGOT, LDH, hematological parameters and biodistribution
      of the nanomaterial at different organ sites. Genotoxicity of samples were done
      by comet assay on blood cells. No significant toxicity was observed in the
      parameters in samples treated group compared to controls. The overall results
      indicated that the CTNPs are nontoxic and is highly stable with improved site
      specific application compared to native curcumin and are suitable for biomedical
      applications.

PMID- 28757139
TI  - Clinical and epidemiological characteristics of human parainfluenza virus
      infections of children in southern Taiwan.
AB  - BACKGROUND: Human parainfluenza viruses (HPIV) 1-4 had been analyzed as being one
      of the most frequent causes of hospitalizations for young children with
      respiratory tract illnesses. METHODS: This retrospective study was performed from
      children virologically confirmed as HPIV infection through throat swab or
      nasopharyngeal aspirates at a tertiary care university hospital, between January
      2012 and December 2014. HPIV4 was not checked and analyzed, due to not include in
      the commercial kit. The demographic, epidemiological, clinical presentations,
      diagnosis, treatment, outcomes, and laboratory data were analyzed. RESULTS:
      Totally 398 cases were enrolled, including 39 (9.8%) of HPIV1, 67 (16.8%) of
      HPIV2, and 292 (73.4%) of HPIV3. The mean age of HPIV-infected children was 2.9
      year-old, and 50.5% were among one to three year-old. A total of 56.8% HPIV3
      infected children were among one to three years old, however, no HPIV2-infected
      children was younger than one year-old. The HPIV1-infected patients were more
      common to develop wheezing and diagnose as acute bronchiolitis. HPIV2-infected
      children were more likely to have hoarseness (23.9%), and were associated with
      croup (25.4%). HPIV3 was isolated from two fatal cases, with neurological
      underlying diseases. CONCLUSION: The impact caused by HPIVs infections is
      significant in hospitalized children. In the current study, our results
      contribute to the epidemiologic, clinical and laboratory information of HPIV
      infection in children in the important areas of respiratory tract infection that
      could support the development of optimization management.

PMID- 28757138
TI  - Early-Life Antibiotic Exposure Causes Intestinal Dysbiosis and Exacerbates Skin
      and Lung Pathology in Experimental Systemic Sclerosis.
AB  - Patients with systemic sclerosis (SSc) display altered intestinal microbiota.
      However, the influence of intestinal dysbiosis on the development of experimental
      SSc remains unknown. Topoisomerase I peptide-loaded dendritic cell immunization
      induces SSc-like disease, with progressive skin and lung fibrosis. Breeders were
      given streptomycin and pups continued to receive antibiotic (ATB) until endpoint
      (lifelongATB). Alternately, ATB was withdrawn (earlyATB) or initiated (adultATB)
      during adulthood. Topoisomerase I peptide-loaded dendritic cell (no ATB)
      immunization induced pronounced skin fibrosis, with increased matrix (Col1a1),
      profibrotic (Il13, Tweakr), and vascular function (Serpine1) gene expression.
      Remarkably, earlyATB exposure was sufficient to augment skin Col5a1 and Il13
      expression, and inflammatory cell infiltration, which included IL-13+ cells,
      mononuclear phagocytes, and mast cells. Moreover, skin pathology exacerbation was
      also observed in lifelongATB and adultATB groups. Oral streptomycin
      administration induced intestinal dysbiosis, with exposure limited to early life
      (earlyATB) being sufficient to cause long-term modification of the microbiota and
      a shift toward increased Bacteroidetes/Firmicutes ratio. Finally, aggravated lung
      fibrosis and dysregulated pulmonary T-cell responses were observed in earlyATB
      and lifelongATB but not adultATB-exposed mice. Collectively, intestinal
      microbiota manipulation with streptomycin exacerbated pathology in two distinct
      sites, skin and lungs, with early life being a critical window to affect the
      course of SSc-like disease.

PMID- 28757140
TI  - The feasibility, safety, and effectiveness of hysteroscopic sterilization
      compared with laparoscopic sterilization.
AB  - BACKGROUND: In contrast to conventional laparoscopic sterilization, newer
      hysteroscopic approaches avoid the need for hospital admission, general
      anesthesia, and prolonged recovery. However, there are concerns that the
      feasibility, safety, and efficacy of hysteroscopic sterilization may be lower
      than established laparoscopic sterilization. OBJECTIVE: We sought to evaluate the
      outcomes of hysteroscopic sterilization compared with laparoscopic sterilization
      in routine clinical practice in a comparative observational cohort study. STUDY
      DESIGN: This study was carried out at University of Birmingham, United Kingdom,
      National Health Service teaching hospital, office hysteroscopy clinics, and day
      case hospital unit. In all, 1085 women underwent hysteroscopic sterilization and
      2412 had laparoscopic sterilization. Hysteroscopic sterilization was carried out
      using the tubal implant permanent birth control system in the office setting and
      laparoscopic sterilization using the tubal ligation system as a day-case under
      general anesthesia. Outcome data were collected regarding feasibility (technical
      completion of the sterilization procedure, satisfactory radiological confirmation
      at 3 months-hysterosalpingogram or transvaginal pelvic ultrasound scan), safety
      events within 30 days of procedures, reoperations, and unintended pregnancies
      within 1 year of procedures. RESULTS: Hysteroscopic sterilization was successful
      in 992/1085 (91.4%; 95% confidence interval, 89.6-93.0%) at the first attempt. In
      comparison, bilateral tubal ligation was successfully performed in 2400/2412
      (99.5%; 95% confidence interval, 99.2-99.8%) of patients who underwent
      laparoscopic sterilizations (odds ratio, 18.8; 95% confidence interval, 10.2
      34.4). In all, 902/1085 (83.1%; 95% confidence interval, 80.8-85.2%) of
      successfully performed hysteroscopic procedures attended for radiological
      confirmation testing were considered satisfactory. The rate of adverse events
      within 30 days were similar: 2/1085 (0.2%) vs 3 (0.12%; 95% confidence interval,
      0.04-0.36%). There were 3/1085 (0.3%; 95% confidence interval, 0.1-0.8%)
      unintended pregnancies after hysteroscopic sterilization compared with 5/2412
      (0.2%; 95% confidence interval, 0.1-0.5%) laparoscopic sterilization (odds ratio,
      1.3; 95% confidence interval, 0.3-5.6). Median length of follow-up for pregnancy
      outcome was 5 years. Hysteroscopic sterilization was associated with a higher
      risk of reoperation at 1 year compared to laparoscopic sterilization (odds ratio,
      6.2; 95% confidence interval, 2.8-14.0) and the commonest reintervention was
      unilateral salpingectomy (12/22, 54.5%). CONCLUSION: Hysteroscopic sterilization
      has been introduced as a more convenient, office-based method of permanent
      fertility control. However, while the small risk of unintended pregnancy is
      comparable to conventional laparoscopic sterilization, women should also be
      counselled regarding its lower success rate in successfully completing the
      procedure and its higher rate of failed reoperation.

PMID- 28757141
TI  - Molecular Epidemiology of a novel re-assorted epidemic strain of equine influenza
      virus in Pakistan in 2015-16.
AB  - BACKGROUND: A widespread epidemic of equine influenza (EI) occurred in
      nonvaccinated equine population across multiple districts in Khyber Pakhtunkhwa
      Province of Pakistan during 2015-2016. OBJECTIVES AND METHODS: An epidemiological
      surveillance study was conducted from Oct 2015 to April 2016 to investigate the
      outbreak. EI virus strains were isolated in embryonated eggs from suspected
      equines swab samples and were subjected to genome sequencing using M13 tagged
      segment specific primers. Phylogenetic analyses of the nucleotide sequences were
      concluded using Geneious. Haemagglutinin (HA), Neuraminidase (NA), Matrix (M) and
      nucleoprotein (NP) genes nucleotide and amino acid sequences of the isolated
      viruses were aligned with those of OIE recommended, FC-1, FC-2, and contemporary
      isolates of influenza A viruses from other species. RESULTS: HA and NA genes
      amino acid sequences were very similar to Tennessee/14 and Malaysia/15 of FC-1
      and clustered with the contemporary isolates recently reported in the USA.
      Phylogenetic analysis showed that these viruses were mostly identical (with 99.6%
      and 97.4% nucleotide homology) to, and were reassortants containing
      chicken/Pakistan/14 (H7N3) and Canine/Beijing/10 (H3N2) like M and NP genes.
      Genetic analysis indicated that A/equine/Pakistan/16 viruses were most probably
      the result of several re-assortments between the co-circulating avian and equine
      viruses, and were genetically unlike the other equine viruses due to the presence
      of H7N3 or H3N2 like M and NP genes. CONCLUSION: Epidemiological data analysis
      indicated the potential chance of mixed, and management such as mixed farming
      system by keeping equine, canine and backyard poultry together in confined
      premises as the greater risk factors responsible for the re-assortments. Other
      factors might have contributed to the spread of the epidemic, including low
      awareness level, poor control of equine movements, and absence of border control
      disease strategies.

PMID- 28757142
TI  - Influenza virus NS1 protein mutations at position 171 impact innate interferon
      responses by respiratory epithelial cells.
AB  - The influenza virus NS1 protein interacts with a wide range of proteins to
      suppress the host cell immune response and facilitate virus replication. The
      amino acid sequence of the 2009 pandemic virus NS1 protein differed from
      sequences of earlier related viruses. The functional impact of these differences
      has not been fully defined. Therefore, we made mutations to the NS1 protein based
      on these sequence differences, and assessed the impact of these changes on host
      cell interferon (IFN) responses. We found that viruses with mutations at position
      171 replicated efficiently but did not induce expression of interferon genes as
      effectively as wild-type viruses in A459 lung epithelial cells. The decreased
      ability of these NS1 mutant viruses to induce IFN gene and protein expression
      correlated with decreased activation of STAT1 and lower levels of IFN-stimulated
      gene (ISG) expression. These findings demonstrate that mutations at position 171
      in the NS1 protein result in decreased expression of IFN and ISGs by A549 cells.
      Consequently, these viruses may be more virulent than the parental strains that
      do not contain mutations at position 171 in the NS1 protein.

PMID- 28757143
TI  - Food challenges.

PMID- 28757144
TI  - Refined Cryo-EM Structure of the T4 Tail Tube: Exploring the Lowest Dose Limit.
AB  - The bacteriophage T4 contractile tail (containing a tube and sheath) was the
      first biological assembly reconstructed in three dimensions by electron
      microscopy at a resolution of ~35 A in 1968. A single-particle reconstruction of
      the T4 baseplate was able to generate a 4.1 A resolution map for the first two
      rings of the tube using the overall baseplate for alignment. We have now
      reconstructed the T4 tail tube at a resolution of 3.4 A, more than a 1,000-fold
      increase in information content for the tube from 1968. We have used legacy
      software (Spider) to show that we can do better than the typical 2/3 Nyquist
      frequency. A reasonable map can be generated with only 1.5 electrons/A2 using the
      higher dose images for alignment, but increasing the dose results in a better
      map, consistent with other reports that electron dose does not represent the main
      limitation on resolution in cryo-electron microscopy.

PMID- 28757145
TI  - Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human
      DHHC17 Palmitoyltransferase.
AB  - DHHC enzymes catalyze palmitoylation, a major post-translational modification
      that regulates a number of key cellular processes. There are up to 24 DHHCs in
      mammals and hundreds of substrate proteins that get palmitoylated. However, how
      DHHC enzymes engage with their substrates is still poorly understood. There is
      currently no structural information about the interaction between any DHHC enzyme
      and protein substrates. In this study we have investigated the structural and
      thermodynamic bases of interaction between the ankyrin repeat domain of human
      DHHC17 (ANK17) and Snap25b. We solved a high-resolution crystal structure of the
      complex between ANK17 and a peptide fragment of Snap25b. Through structure-guided
      mutagenesis, we discovered key residues in DHHC17 that are critically important
      for interaction with Snap25b. We further extended our finding by showing that the
      same residues are also crucial for the interaction of DHHC17 with Huntingtin, one
      of its most physiologically relevant substrates.

PMID- 28757146
TI  - Regulation of Receptor Binding Specificity of FGF9 by an Autoinhibitory
      Homodimerization.
AB  - The epithelial fibroblast growth factor 9 (FGF9) subfamily specifically binds and
      activates the mesenchymal "c" splice isoform of FGF receptors 1-3 (FGFR1-3) to
      regulate organogenesis and tissue homeostasis. The unique N and C termini of FGF9
      subfamily ligands mediate a reversible homodimerization that occludes major
      receptor binding sites within the ligand core region. Here we provide compelling
      X-ray crystallographic, biophysical, and biochemical data showing that
      homodimerization controls receptor binding specificity of the FGF9 subfamily by
      keeping the concentration of active FGF9 monomers at a level, which is sufficient
      for a normal FGFR "c" isoform binding/signaling, but is insufficient for an
      illegitimate FGFR "b" isoform binding/signaling. We show that deletion of the N
      terminus or alanine substitutions in the C terminus of FGF9 skews the delicate
      ligand equilibrium toward active FGF9 monomers causing off-target binding and
      activation of FGFR b isoforms. Our study is the first to implicate ligand
      homodimerization in the regulation of ligand-receptor specificity.

PMID- 28757147
TI  - Steering Soil Microbiomes to Suppress Aboveground Insect Pests.
AB  - Soil-borne microbes affect aboveground herbivorous insects through a cascade of
      molecular and chemical changes in the plant, but knowledge of these microbe-plant
      insect interactions is mostly limited to one or a few microbial strains. Yet, the
      soil microbial community comprises thousands of unique taxa interacting in
      complex networks, the so-called 'microbiome', which provides plants with multiple
      beneficial functions. There has been little exploration of the role and
      management of whole microbiomes in plant-insect interactions, calling for the
      integration of this complexity in aboveground-belowground research. Here, we
      propose holistic approaches to select soil microbiomes that can be used to
      protect plants from aboveground attackers.

PMID- 28757149
TI  - Motivation and short-term memory in visual search: Attention's accelerator
      revisited.
AB  - A cue indicating the possibility of cash reward will cause participants to
      perform memory-based visual search more efficiently. A recent study has suggested
      that this performance benefit might reflect the use of multiple memory systems:
      when needed, participants may maintain the to-be-remembered object in both long
      term and short-term visual memory, with this redundancy benefitting target
      identification during search (Reinhart, McClenahan & Woodman, 2016). Here we test
      this compelling hypothesis. We had participants complete a memory-based visual
      search task involving a reward cue that either preceded presentation of the to-be
      remembered target (pre-cue) or followed it (retro-cue). Following earlier work,
      we tracked memory representation using two components of the event-related
      potential (ERP): the contralateral delay activity (CDA), reflecting short-term
      visual memory, and the anterior P170, reflecting long-term storage. We
      additionally tracked attentional preparation and deployment in the contingent
      negative variation (CNV) and N2pc, respectively. Results show that only the
      reward pre-cue impacted our ERP indices of memory. However, both types of cue
      elicited a robust CNV, reflecting an influence on task preparation, both had
      equivalent impact on deployment of attention to the target, as indexed in the
      N2pc, and both had equivalent impact on visual search behavior. Reward prospect
      thus has an influence on memory-guided visual search, but this does not appear to
      be necessarily mediated by a change in the visual memory representations indexed
      by CDA. Our results demonstrate that the impact of motivation on search is not a
      simple product of improved memory for target templates.

PMID- 28757148
TI  - Transdiagnostic psychiatric disorder risk associated with early age of menarche:
      A latent modeling approach.
AB  - BACKGROUND: Earlier age of pubertal maturation in females is associated with
      increased risk for mental health problems in adolescence, compared with on-time
      or later maturation. However, most investigations of pubertal timing and mental
      health consider risk for individual disorders and fail to account for
      comorbidity. A latent-modeling approach using a large, nationally representative
      sample could better explain the transdiagnostic nature of the consequences of
      early-onset puberty. METHODS: Data on age of menarche and mental disorders were
      drawn from a population-representative sample of adolescents (n=4925), ages 13
      17. Confirmatory factor analysis was used to fit four latent disorder categories:
      distress, eating, and externalizing, and fear disorders. Timing of menarche
      included those with earlier (age<=10, age 11) and later age of onset (age 13,
      14+), relative to those with average timing of menarche (age 12). Associations
      between timing of menarche and latent disorders were estimated in a structural
      equation model (SEM), adjusted for age, income, race, parent marital status, BMI,
      and childhood adversity. RESULTS: The measurement model evidenced acceptable fit
      (CFI=0.91; RMSEA=0.02). Onset of menarche before age 11 was significantly
      associated with distress disorders (coefficient=0.096; p<0.0001), fear disorders
      (coefficient=0.09; p<0.0001), and externalizing disorders (coefficient=0.039;
      p=0.049) as compared to on-time or late menarche. No residual associations of
      early menarche with individual disorders over and above the latent disorders were
      observed. CONCLUSION: The latent modeling approach illuminated meaningful
      transdiagnostic psychiatric associations with early timing of menarche.
      Biological processes initiated at puberty can influence cognitive and affective
      processes as well as social relationships for adolescents. Under developmentally
      normative conditions, these changes may be adaptive. However, for those out of
      sync with their peers, researchers and clinicians should recognize the potential
      for these processes to influence liability to a broad array of psychopathological
      consequences in adolescence.

PMID- 28757151
TI  - Run-in Periods in Randomized Clinical Trials.

PMID- 28757150
TI  - Temporal Differences in Outcomes During Long-Term Mechanical Circulatory Support.
AB  - BACKGROUND: Device indications have changed for placement of continuous-flow left
      ventricular assist devices (CF-LVADs). We performed a multicenter analysis
      evaluating temporal variations in outcomes after CF-LVAD implantation. METHODS &
      RESULTS: We retrospectively defined 3 time intervals to reflect changes in CF
      LVAD technology (period 1, 2004-2009; period 2, 2010-2012; and period 3, 2012
      2014). A total of 1,064 patients (Heartmate II [HMII] = 835; Heartware [HVAD] =
      229) underwent CF-LVAD implantation from May 2004 to October 2014. Device
      utilization was different between periods: period 1: HMII = 134 (100%); period 2:
      HMII = 480 (88%) and HW = 63 (12%); and period 3: HMII = 221 (57%) and HW = 166
      (43%); P < .001. Despite few baseline group differences, adjusted survivals were
      similar among the time periods (P = .96). Adjusted multivariable analysis
      revealed age (per 10-year increase) and Interagency Registry for Mechanically
      Assisted Circulatory Support category (1 vs all others) as the only independent
      predictors of mortality: P < .001 and P = .008, respectively. Furthermore, it
      also showed the later periods to be at an increased risk of adverse events: 1)
      pump thrombosis (periods 2 and 3); and 2) gastrointestinal bleeding (period 3).
      CONCLUSIONS: Despite significant differences in device types, indications, and
      patient characteristics, post-implantation survivals were similar across time
      intervals. The most recent cohort seems to be at an increased risk of
      gastrointestinal bleeding and pump thrombosis.

PMID- 28757152
TI  - Where Patients With Heart Failure Die: Trends in Location of Death of Patients
      With Heart Failure in the United States.

PMID- 28757153
TI  - Hemodynamic Determinants of the Biologic Variation of N-Terminal Pro-B-Type
      Natriuretic Peptide in Patients With Stable Systolic Chronic Heart Failure.
AB  - BACKGROUND CONTEXT: Biologic variation of N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) in chronic heart failure (CHF) may affect blood levels and
      risk stratification. The sources of NT-proBNP variation are unknown. METHODS AND
      RESULTS: We performed NT-proBNP measurements and clinical and hemodynamic
      assessments in 50 patients with heart failure with reduced ejection fraction
      (HFrEF) who met criteria for clinical stability over 2 time intervals.
      Hemodynamic variables were measured with the use of inert gas rebreathing and
      impedance cardiography. Heart rhythm was monitored with the use of external
      electrocardiographic event recorders throughout the study. Determinants of NT
      proBNP-levels and both absolute (DeltaNT-proBNPabs) and relative (DeltaNT
      proBNP%) changes at 1-week and 2-week intervals were identified with the use of
      univariable and multivariable linear mixed-effects models and linear regression
      analyses, respectively. Clinical and hemodynamic variables did not significantly
      change between study visits. The individual variation of NT-proBNP at 2 weeks was
      9.2% (range 3.9%-18.6%). Weight and glomerular filtration rate were independently
      associated with baseline NT-proBNP concentrations (P = .01 and P = .005,
      respectively). There was no relationship between absolute and relative changes of
      NT-proBNP at 1-week intervals and changes in clinical and hemodynamic variables.
      Absolute change of NT-proBNP at 2-week intervals was associated with absolute
      change in left cardiac work index (P = .008), and relative change in NT-proBNP at
      2-week intervals was determined by relative change of thoracic fluid content
      index (P = .008) and diastolic blood pressure (P = .01). The coefficients of
      determination (R2) for the multivariable models with Delta1wkNT-proBNPabs, Delta2
      weeksNT-proBNPabs, Delta1wkNT-proBNP%, and Delta2wksNT-proBNP% as dependent
      variables were 0.21, 0.19, 0.10, and 0.32, respectively. CONCLUSIONS: In patients
      with stable HFrEF, changes in clinical and hemodynamic variables only marginally
      contribute to the variation of NT-proBNP.

PMID- 28757154
TI  - The central serotonin2B receptor as a new pharmacological target for the
      treatment of dopamine-related neuropsychiatric disorders: Rationale and current
      status of research.
AB  - The serotonin2B receptor (5-HT2BR), which was first cloned and characterized in
      the rat stomach fundus, is the most recent addition to the 5-HT2R family. While
      its involvement in the regulation of gastrointestinal, vascular, pulmonary and
      cardiac physiology has been widely investigated, its functional role within the
      central nervous system (CNS) has received much less attention. Nevertheless, when
      considering the data available in the literature with regards to the regulatory
      control exerted by the central 5-HT2BR on dopamine (DA) and serotonin (5-HT)
      neuron activity, a very interesting picture emerges and highlights the key role
      of these receptors for future therapeutic strategies of DA-related
      neuropsychiatric disorders. Thus, the present review, by compiling molecular,
      biochemical, electrophysiological and behavioral findings from the literature of
      the past twenty years, aims at providing a sound analysis of the current
      knowledge supporting the interest of the central 5-HT2BR for future therapeutic
      avenues. First, we recall the neuroanatomical and functional data supporting the
      therapeutic relevance of the 5-HT/DA interaction in the CNS. Thereafter, after a
      short overview of the central expression and molecular properties of the 5-HT2BR,
      as well as of the 5-HT2BR agonists and antagonists available in the market, we
      will focus on the functional role of this receptor in the control of 5-HT, DA and
      neuroglia activity in the rodent brain. Finally, the therapeutic potential of 5
      HT2BR antagonists for improved treatment of schizophrenia and drug addiction will
      be discussed.

PMID- 28757155
TI  - Antibody drug conjugates for treatment of breast cancer: Novel targets and
      diverse approaches in ADC design.
AB  - Breast cancer is a heterogeneous group of malignancies with a spectrum of
      molecular subtypes, pathologies and outcomes that together comprise the most
      common non-cutaneous cancer in women. Currently, over 80% of breast cancer
      patients are diagnosed at relatively early stages of disease where there are
      encouraging data on outcomes and long term survival. However, there is currently
      no curative option for those patients with metastatic disease and there is a
      substantial medical need to identify effective and safe treatment options for
      these patients. One approach to improve cancer therapy is by designing
      therapeutics directed against targets with differential levels of expression on
      malignant versus normal cells with the goal of improving tumor selectivity and
      reducing damage to normal tissues. Antibody drug conjugates (ADCs) are a rapidly
      evolving therapeutic class that exploits the target-selectivity of monoclonal
      antibodies (MAbs) to deliver cytotoxic drugs to antigen-expressing cells (Lambert
      & Morris, 2017; Senter, 2009; Thomas, Teicher, & Hassan, 2016; Trail, 2013). The
      regulatory approval of ADCs for both hematologic malignancies (brentuximab
      vedotin) (Younes et al., 2010) and solid tumors (ado-trastuzumab emtansine)
      (Amiri-Kordestani et al., 2014; Verma et al., 2012) clearly demonstrates the
      clinical potential of ADCs. This review will focus on targets under consideration
      for breast cancer directed ADCs and on the technology modifications being
      considered to improve ADC efficacy and safety.

PMID- 28757156
TI  - Emerging understanding of the mechanism of action of Bronchial Thermoplasty in
      asthma.
AB  - Bronchial Thermoplasty (BT) is an endoscopic treatment for moderate-to-severe
      asthma patients who are uncontrolled despite optimal medical therapy.
      Effectiveness of BT has been demonstrated in several randomized clinical trials.
      However, the asthma phenotype that benefits most of this treatment is unclear,
      partly because the mechanism of action is incompletely understood. BT was
      designed to reduce the amount of airway smooth muscle (ASM), but additional
      direct and indirect effects on airway pathophysiology are expected. This review
      will provide an overview of the different components of airway pathophysiology
      including remodeling, with the ASM as the key player. Current concepts in the
      understanding of BT clinical effectiveness with a focus on its impact on airway
      remodeling will be reviewed.

PMID- 28757158
TI  - A short term high-fat high-sucrose diet in mice impairs optic nerve recovery
      after injury and this is not reversed by exercise.
AB  - The aim of the current work was to test whether increased intake of dietary fat
      and sucrose in mice modifies the response of retinal ganglion cells (RGCs) of the
      optic nerve to injury, and whether any effects of diet are influenced by physical
      activity levels. C57BL/6J mice were given a high-fat high-sucrose (HFS) diet for
      7 weeks, with or without exposure to regular exercise by swimming (60 min/day, 5
      days/week). Injury to RGCs was subsequently induced by acute elevation of
      intraocular pressure (IOP) and retinas were assessed for function and structure.
      We report that mice on a HFS diet had similar body mass and blood glucose levels
      compared to mice on a control diet but suffered a 30% greater loss of RGC
      function following injury, as measured in vivo with the electroretinogram. RGC
      dysfunction in retinas from mice on the HFS diet was accompanied by activation of
      retinal macroglia but was not associated with neuronal cell loss. Exercising mice
      by swimming did not prevent HFS-induced RGC dysfunction in response to injury.
      This study shows for the first time that a short term increase in dietary fat and
      sucrose enhances the vulnerability of RGCs to dysfunction and cell stress after
      an acute injury, and that this is independent of obesity or hyperglycemia.
      Furthermore, our results suggest that detrimental effects of diet predominate
      over protective effects of exercise.

PMID- 28757157
TI  - The first complete genomes of Metalmarks and the classification of butterfly
      families.
AB  - Sequencing complete genomes of all major phylogenetic groups of organisms opens
      unprecedented opportunities to study evolution and genetics. We report draft
      genomes of Calephelis nemesis and Calephelis virginiensis, representatives of the
      family Riodinidae. They complete the genomic coverage of butterflies at the
      family level. At 809 and 855 Mbp, respectively, they become the largest available
      Lepidoptera genomes. Comparison of butterfly genomes shows that the divergence
      between Riodinidae and Lycaenidae dates to the time when other families started
      to diverge into subfamilies. Thus, Riodinidae may be considered a subfamily of
      Lycaenidae. Calephelis species exhibit unique gene expansions in actin
      disassembling factor, cofilin, and chitinase. The functional implications of
      these gene expansions are not clear, but they may aid molting of caterpillars
      covered in extensive setae. The two Calephelis species diverged about 5 million
      years ago and they differ in proteins involved in metabolism, circadian clock,
      regulation of development, and immune responses.

PMID- 28757159
TI  - Effectivity of oral recombinant DNA vaccine against Streptococcus agalactiae in
      Nile tilapia.
AB  - The effects of oral vaccination by two immune routes (gavage and mixed fodder
      administration) using a recombinant DNA vaccine SL7207-pVAX1-sip against
      Streptococcus agalactiae were assessed. SL7207-pVAX1-sip significantly enhanced
      various innate immune responses of tilapia, such as total serum protein,
      superoxide dismutase activity, lysozyme activity, complement C3 concentration in
      serum, serum antibacterial activity, and interleukin 1beta and tumor necrosis
      factor-alpha. Vaccinated fish had higher relative percent survival values (57%
      and 63% for gavage group and mix fodder administration, respectively) at 10 weeks
      after S. agalactiae infection. When administered mixed fodder, the DNA vaccine
      SL7207-pVAX1-sip against S. agalactiae may produce more effective protection.
      These findings can promote the application and development of DNA vaccines in
      aquaculture.

PMID- 28757160
TI  - Mitochondrial impairments contribute to spatial learning and memory dysfunction
      induced by chronic tramadol administration in rat: Protective effect of physical
      exercise.
AB  - Despite the worldwide use of tramadol, few studies have been conducted about its
      effects on memory and mitochondrial function, and controversial results have been
      reported. Recently, there has been an increasing interest in physical exercise as
      a protective approach to neuronal and cognitive impairments. Therefore, the aim
      of this study was to investigate the effects of physical exercise on spatial
      learning and memory and brain mitochondrial function in tramadol-treated rats.
      After completion of 2-week (short-term) and 4-week (long-term) treadmill exercise
      regimens, male Wistar rats received tramadol (20, 40, 80mg/kg/day)
      intraperitoneally for 30days. Then spatial learning and memory was assessed by
      Morris water maze test (MWM). Moreover, brain mitochondrial function was
      evaluated by determination of mitochondrial reactive oxygen species (ROS) level,
      mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c
      release from mitochondria. Chronic administration of tramadol impaired spatial
      learning and memory as well as brain mitochondrial function as indicated by
      increased ROS level, MMP collapse, increased mitochondrial swelling and
      cytochrome c release from mitochondria. Conversely, treadmill exercise
      significantly attenuated the impairments of spatial learning and memory and brain
      mitochondrial dysfunction induced by tramadol. The results revealed that chronic
      tramadol treatment caused memory impairments through induction of brain
      mitochondrial dysfunction. Furthermore, pre-exposure to physical exercise
      markedly mitigated these impairments through its positive effects on brain
      mitochondrial function.

PMID- 28757162
TI  - An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal
      Cells.
AB  - During liver development, hepatoblasts and liver non-parenchymal cells (NPCs)
      such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells
      (HSCs) constitute the liver bud where they proliferate and differentiate.
      Accordingly, we reasoned that liver NPCs would support the maturation of
      hepatocytes derived from human induced pluripotent stem cells (hiPSCs), which
      usually exhibit limited functions. We found that the transforming growth factor
      beta and Rho signaling pathways, respectively, regulated the proliferation and
      maturation of LSEC and HSC progenitors isolated from mouse fetal livers. Based on
      these results, we have established culture systems to generate LSECs and HSCs
      from hiPSCs. These hiPSC-derived NPCs exhibited distinctive phenotypes and
      promoted self-renewal of hiPSC-derived liver progenitor cells (LPCs) over the
      long term in the two-dimensional culture system without exogenous cytokines and
      hepatic maturation of hiPSC-derived LPCs. Thus, a functional human liver model
      can be constructed in vitro from the LPCs, LSECs, and HSCs derived from hiPSCs.

PMID- 28757161
TI  - Adventitial SCA-1+ Progenitor Cell Gene Sequencing Reveals the Mechanisms of Cell
      Migration in Response to Hyperlipidemia.
AB  - Adventitial progenitor cells, including SCA-1+ and mesenchymal stem cells, are
      believed to be important in vascular remodeling. It has been shown that SCA-1+
      progenitor cells are involved in neointimal hyperplasia of vein grafts, but
      little is known concerning their involvement in hyperlipidemia-induced
      atherosclerosis. We employed single-cell sequencing technology on primary
      adventitial mouse SCA-1+ cells from wild-type and atherosclerotic-prone (ApoE
      deficient) mice and found that a group of genes controlling cell migration and
      matrix protein degradation was highly altered. Adventitial progenitors from ApoE
      deficient mice displayed an augmented migratory potential both in vitro and in
      vivo. This increased migratory ability was mimicked by lipid loading to SCA-1+
      cells. Furthermore, we show that lipid loading increased miRNA-29b expression and
      induced sirtuin-1 and matrix metalloproteinase-9 levels to promote cell
      migration. These results provide direct evidence that blood cholesterol levels
      influence vascular progenitor cell function, which could be a potential target
      cell for treatment of vascular disease.

PMID- 28757163
TI  - Evaluating Synthetic Activation and Repression of Neuropsychiatric-Related Genes
      in hiPSC-Derived NPCs, Neurons, and Astrocytes.
AB  - Modulation of transcription, either synthetic activation or repression, via dCas9
      fusion proteins is a relatively new methodology with the potential to facilitate
      high-throughput up- or downregulation studies of gene function. Genetic studies
      of neurodevelopmental disorders have identified a growing list of risk variants,
      including both common single-nucleotide variants and rare copy-number variations,
      many of which are associated with genes having limited functional annotations. By
      applying a CRISPR-mediated gene-activation/repression platform to populations of
      human-induced pluripotent stem cell-derived neural progenitor cells, neurons, and
      astrocytes, we demonstrate that it is possible to manipulate endogenous
      expression levels of candidate neuropsychiatric risk genes across these three
      cell types. Although proof-of-concept studies using catalytically inactive Cas9
      fusion proteins to modulate transcription have been reported, here we present a
      detailed survey of the reproducibility of gRNA positional effects across a
      variety of neurodevelopmental disorder-relevant risk genes, donors, neural cell
      types, and dCas9 effectors.

PMID- 28757164
TI  - Surface Topography Guides Morphology and Spatial Patterning of Induced
      Pluripotent Stem Cell Colonies.
AB  - The relevance of topographic cues for commitment of induced pluripotent stem
      cells (iPSCs) is largely unknown. In this study, we demonstrate that groove-ridge
      structures with a periodicity in the submicrometer range induce elongation of
      iPSC colonies, guide the orientation of apical actin fibers, and direct the
      polarity of cell division. Elongation of iPSC colonies impacts also on their
      intrinsic molecular patterning, which seems to be orchestrated from the rim of
      the colonies. BMP4-induced differentiation is enhanced in elongated colonies, and
      the submicron grooves impact on the spatial modulation of YAP activity upon
      induction with this morphogen. Interestingly, TAZ, a YAP paralog, shows distinct
      cytoskeletal localization in iPSCs. These findings demonstrate that topography
      can guide orientation and organization of iPSC colonies, which may affect the
      interaction between mechanosensors and mechanotransducers in iPSCs.

PMID- 28757165
TI  - An Efficient Platform for Astrocyte Differentiation from Human Induced
      Pluripotent Stem Cells.
AB  - Growing evidence implicates the importance of glia, particularly astrocytes, in
      neurological and psychiatric diseases. Here, we describe a rapid and robust
      method for the differentiation of highly pure populations of replicative
      astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural
      progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC
      lines (derived from 30 individuals). Transcriptomic analysis demonstrated that
      hiPSC-astrocytes from four individuals are highly similar to primary human fetal
      astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond
      to inflammatory stimulants, display phagocytic capacity, and enhance microglial
      phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient
      activity. Our protocol is a reproducible, straightforward (single medium), and
      rapid (<30 days) method to generate populations of hiPSC-astrocytes that can be
      used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of
      neuropsychiatric disorders.

PMID- 28757166
TI  - p53 Mediates Failure of Human Definitive Hematopoiesis in Dyskeratosis Congenita.
AB  - Dyskeratosis congenita (DC) is a bone marrow failure syndrome associated with
      telomere dysfunction. The progression and molecular determinants of hematopoietic
      failure in DC remain poorly understood. Here, we use the directed differentiation
      of human embryonic stem cells harboring clinically relevant mutations in
      telomerase to understand the consequences of DC-associated mutations on the
      primitive and definitive hematopoietic programs. Interestingly, telomere
      shortening does not broadly impair hematopoiesis, as primitive hematopoiesis is
      not impaired in DC cells. In contrast, while phenotypic definitive hemogenic
      endothelium is specified, the endothelial-to-hematopoietic transition is impaired
      in cells with shortened telomeres. This failure is caused by DNA damage accrual
      and is mediated by p53 stabilization. These observations indicate that
      detrimental effects of telomere shortening in the hematopoietic system are
      specific to the definitive hematopoietic lineages. This work illustrates how
      telomere dysfunction impairs hematopoietic development and creates a robust
      platform for therapeutic discovery for treatment of DC patients.

PMID- 28757167
TI  - Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a
      Single Transcription Factor.
AB  - Liver or hepatocytes transplantation is limited by the availability of donor
      organs. Functional hepatocytes independent of the donor sources may have wide
      applications in regenerative medicine and the drug industry. Recent studies have
      demonstrated that chemical cocktails may induce reprogramming of fibroblasts into
      a range of functional somatic cells. Here, we show that mouse fibroblasts can be
      transdifferentiated into the hepatocyte-like cells (iHeps) using only one
      transcription factor (TF) (Foxa1, Foxa2, or Foxa3) plus a chemical cocktail.
      These iHeps show typical epithelial morphology, express multiple hepatocyte
      specific genes, and acquire hepatocyte functions. Genetic lineage tracing
      confirms the fibroblast origin of these iHeps. More interestingly, these iHeps
      are expandable in vitro and can reconstitute the damaged hepatic tissues of the
      fumarylacetoacetate hydrolase-deficient (Fah-/-) mice. Our study provides a
      strategy to generate functional hepatocyte-like cells by using a single TF plus a
      chemical cocktail and is one step closer to generate the full-chemical iHeps.

PMID- 28757168
TI  - Hippocampal TERT Regulates Spatial Memory Formation through Modulation of Neural
      Development.
AB  - The molecular mechanism of memory formation remains a mystery. Here, we show that
      TERT, the catalytic subunit of telomerase, gene knockout (Tert-/-) causes
      extremely poor ability in spatial memory formation. Knockdown of TERT in the
      dentate gyrus of adult hippocampus impairs spatial memory processes, while
      overexpression facilitates it. We find that TERT plays a critical role in neural
      development including dendritic development and neuritogenesis of hippocampal
      newborn neurons. A monosynaptic pseudotyped rabies virus retrograde tracing
      method shows that TERT is required for neural circuit integration of hippocampal
      newborn neurons. Interestingly, TERT regulated neural development and spatial
      memory formation in a reverse transcription activity-independent manner. Using X
      ray irradiation, we find that hippocampal newborn neurons mediate the modulation
      of spatial memory processes by TERT. These observations reveal an important
      function of TERT through a non-canonical pathway and encourage the development of
      a TERT-based strategy to treat neurological disease-associated memory impairment.

PMID- 28757170
TI  - The deleterious interplay between tumor epithelia and stroma in
      cholangiocarcinoma.
AB  - Prognosis of cholangiocarcinoma, a devastating liver epithelial malignancy
      characterized by early invasiveness, remains very dismal, though its incidence
      has been steadily increasing. Evidence is mounting that in cholangiocarcinoma,
      tumor epithelial cells establish an intricate web of mutual interactions with
      multiple stromal components, largely determining the pervasive behavior of the
      tumor. The main cellular components of the tumor microenvironment (i.e.
      myofibroblasts, macrophages, lymphatic endothelial cells), which has been
      recently termed as 'tumor reactive stroma', are recruited and activated by
      neoplastic cells, and in turn, deleteriously mold tumor behavior by releasing a
      huge variety of paracrine signals, including cyto/chemokines, growth factors,
      morphogens and proteinases. An abnormally remodeled and stiff extracellular
      matrix favors and supports these cell interactions. Although the mechanisms
      responsible for the generation of tumor reactive stroma are largely uncertain,
      hypoxia presumably plays a central role. In this review, we will dissect the
      intimate relationship among the different cell elements cooperating within this
      complex 'ecosystem', with the ultimate goal to pave the way for a deeper
      understanding of the mechanisms underlying cholangiocarcinoma aggressiveness, and
      possibly, to foster the development of innovative, combinatorial therapies aimed
      at halting tumor progression. This article is part of a Special Issue entitled:
      Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni,
      Nicholas LaRusso and Peter Jansen.

PMID- 28757171
TI  - Genetic determinants of cholangiopathies: Molecular and systems genetics.
AB  - Familial cholangiopathies are rare but potentially severe diseases. Their
      spectrum ranges from fairly benign conditions as, for example, benign recurrent
      intrahepatic cholestasis to low-phospholipid associated cholelithiasis and
      progressive familial intrahepatic cholestasis (PFIC). Many cholangiopathies such
      as primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC)
      affect first the bile ducts ("ascending pathophysiology") but others, such as
      PFIC, start upstream in hepatocytes and cause progressive damage "descending"
      down the biliary tree and leading to end-stage liver disease. In recent years our
      understanding of cholestatic diseases has improved, since we have been able to
      pinpoint numerous disease-causing mutations that cause familial cholangiopathies.
      Accordingly, six PFIC subtypes (PFIC type 1-6) have now been defined. Given the
      availability of genotyping resources, these findings can be introduced in the
      diagnostic work-up of patients with peculiar cholestasis. In addition, functional
      studies have defined the pathophysiological consequences of some of the detected
      variants. Furthermore, ABCB4 variants do not only cause PFIC type 3 but confer an
      increased risk for chronic liver disease in general. In the near future these
      findings will serve to develop new therapeutic strategies for patients with liver
      diseases. Here we present the latest data on the genetic background of familial
      cholangiopathies and discuss their application in clinical practice for the
      differential diagnosis of cholestasis of unknown aetiology. As look in the future
      we present "system genetics" as a novel experimental tool for the study of
      cholangiopathies and disease-modifying genes. This article is part of a Special
      Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales,
      Marco Marzioni, Nicholas LaRusso and Peter Jansen.

PMID- 28757169
TI  - Mir-29b Mediates the Neural Tube versus Neural Crest Fate Decision during
      Embryonic Stem Cell Neural Differentiation.
AB  - During gastrulation, the neuroectoderm cells form the neural tube and neural
      crest. The nervous system contains significantly more microRNAs than other
      tissues, but the role of microRNAs in controlling the differentiation of
      neuroectodermal cells into neural tube epithelial (NTE) cells and neural crest
      cells (NCCs) remains unknown. Using embryonic stem cell (ESC) neural
      differentiation systems, we found that miR-29b was upregulated in NTE cells and
      downregulated in NCCs. MiR-29b promoted the differentiation of ESCs into NTE
      cells and inhibited their differentiation into NCCs. Accordingly, the inhibition
      of miR-29b significantly inhibited the differentiation of NTE cells. A
      mechanistic study revealed that miR-29b targets DNA methyltransferase 3a (Dnmt3a)
      to regulate neural differentiation. Moreover, miR-29b mediated the function of
      Pou3f1, a critical neural transcription factor. Therefore, our study showed that
      the Pou3f1-miR-29b-Dnmt3a regulatory axis was active at the initial stage of
      neural differentiation and regulated the determination of cell fate.

PMID- 28757172
TI  - Polyphyllin VII increases sensitivity to gefitinib by modulating the elevation of
      P21 in acquired gefitinib resistant non-small cell lung cancer.
AB  - Blockade of EGFR with reversible EGFR tyrosine kinase inhibitors (TKIs) is
      considered the frontline strategy for advanced NSCLC with EGFR mutations.
      However, acquired resistance to EGFR-TKI has been observed, resulting in disease
      progression and limited clinical benefit. Polyphyllin VII is the main member of
      polyphyllin family, which has been demonstrated to show strong anticancer
      activity against carcinomas. The sensitizing effect and underlying mechanism of
      Polyphyllin VII against acquired EGFR-TKI resistant NSCLC are still unexplored.
      In the present study, we aim to examined the sensitizing effect of Polyphyllin
      VII to gefitinib by modulating P21 signaling pathway in gefitinib acquired
      resistant NSCLC in vitro and in vivo. Gefitinib sensitive PC-9 cells and
      gefitinib acquired resistant H1975 cells were used. Cell proliferation and
      Clonogenic assay, Cell cycle analysis, Western blotting analysis and xenograft
      treatment were carried out. Polyphyllin VII enhanced the anti-proliferative
      effects of gefitinib and gefitinib-induced G1 phase arrest by modulation of P21
      signaling pathway in acquired gefitinib resistant cells in vitro and in vivo.
      Polyphyllin VII elevated sensitization of gefitinib acquired resistant NSCLC
      cells to gefitinib through G1 phase arrest and modulation of P21 signaling
      pathway. It provides a potential new strategy to overcome gefitinib acquired
      resistance for EGFR-TKI resistant NSCLC.

PMID- 28757173
TI  - Are patients with bladder oversensitivity different from those with
      urodynamically proven detrusor overactivity in female overactive bladder
      syndrome?
AB  - BACKGROUND: To determine if there are clinical and urodynamic (UD) differences
      between female overactive bladder (OAB) patients with bladder oversensitivity
      (BO) and detrusor overactivity (DO) via a much lower filling rate. METHODS: In
      total, 205 patients with OAB symptoms were recruited for this study. During
      filling cystometry, the bladder was filled at a more "physiological" rate of 20
      ml/min. All patients underwent a complete urogynecological evaluation including
      detailed history, physical examination, urinalysis, pad test for quantification
      of urine leakage, 3-day frequency-volume chart (FVC) documentation, and
      completion of a UD study. RESULTS: The overall incidence of BO was 34.2% and that
      of DO was 65.8%. The first desire to void (FDV) in patients with BO and DO were
      at filling of 117.47 +/- 21.68 ml and 135.23 +/- 22.88 ml, respectively (p <
      0.05). Maximal cystometric capacities (MCC) in patients with BO and DO were
      recorded at 259.44 +/- 33.87 ml and 265.32 +/- 44.05 ml (p > 0.05). A receiver
      operating characteristic (ROC) curve was used to find the cut-off values of FDV
      for sensitivity and specificity in patients diagnosed with DO. Area under the
      curve (AUC) was 0.702 (p < 0.005, 95% confidence interval: 0.626-0.779) if FDV
      was determined as more than 127 ml. Patients with BO experienced significantly
      increased daytime urinary frequency and nocturia symptoms (<0.05). Patients with
      DO had a significantly higher prevalence of urgent urinary incontinence (p <
      0.05). In this study, a higher FDV and higher body mass index (BMI) were
      correlating factors for OAB patients with DO after multiple logistic regression
      analysis. CONCLUSION: Patients with BO seemed to be on a different spectrum
      compared to those with DO and also had different symptom-specific and associative
      factors. It was also found that FDV could be good predictive indicator for
      detecting DO at a low filling rate.

PMID- 28757174
TI  - [Atrial fibrillation: Thromboembolic risk factor or marker? From concept to
      therapy].
AB  - The main complication of atrial fibrillation is stroke. Twenty years ago, the
      interest of vitamin K antagonist has been clearly demonstrated but these drugs
      are difficult to manage. For the last 10 years, direct oral anticoagulants have
      been developed. These drugs have demonstrated a non-inferiority as compared to
      vitamin K antagonist and a clear decrease in intra cerebral hemorrhages.
      Anticoagulation is indicated in a large majority of patients with atrial
      fibrillation. Nevertheless, many points remained questionable, like the
      anticoagulation of low risk patients, the choice of oral anticoagulants dosages,
      the anticoagulation according to the type of atrial fibrillation and the strategy
      in coronary artery disease patients for example. Recently it has been
      demonstrated that in many patients there were no temporal relationship between
      the occurrence of atrial fibrillation episodes and stroke. That means that in
      many cases atrial fibrillation is not the factor but the marker of thromboembolic
      risk.

PMID- 28757175
TI  - [Main novelties of the last set of European guidelines for the management of
      heart failure].
AB  - Heart failure is the main chronic disease in cardiology. Its prognosis remains
      poor despite improvements in its management that allow patients to live
      increasingly longer with this disease, alternating periods of stability and
      episodes of decompensation. Treatment guidelines are regularly updated to
      integrate new results of recent trials that are likely to influence routine care.
      These guidelines are proposed with different classes of recommendations and
      difference levels of evidence. It is of paramount importance to summarize the
      guidelines to make them accessible to the vast majority of cardiologists and
      easier to read to promote their application. Among the main novelties of the last
      set of European guidelines for the management of heart failure, we note the
      proposal for a new classification based on the level of left ventricular ejection
      fraction (LVEF) with a new class, called heart failure with mid-range ejection
      fraction (LVEF 40-50 %), new algorithms for diagnosis and treatment, including
      the diagnosis of heart failure with preserved ejection fraction, a special focus
      on preventive strategies, the management of comorbidities including iron
      deficiency, simplification of the indications for cardiac resynchronization
      therapy, and finally a growing attention to patient pathways and to the
      management of hospital discharge. According to these guidelines, it is important
      that the physician choose the appropriate medications; but it is equally
      fundamental that the patient understands the disease and acquires self-care
      skills needed to become a real player in its management. This requires patient
      education, which is underdeveloped in France.

PMID- 28757176
TI  - [Occupational sedentary behaviors and physical activity at work].
AB  - Sedentary behaviors are a leading cause of preventable mortality in developed
      countries. We mainly have sedentary behaviors at work. Sedentary behaviors must
      be considered as an occupational risk, and therefore must be a major concern for
      managers and physicians/health researchers. Recreational physical activity only
      partly compensates for the negative effects of physical inactivity at work.
      Physical activity at work without excess (walking, standing) is beneficial.
      Initiatives to reduce physical inactivity and increase physical activity among
      employees are effective in terms of mental health, physical health, and
      productivity. Prevention of sedentary behaviors at work is a win-win partnership
      between employers and employees.

PMID- 28757177
TI  - Acute necrotic pancreatitis: A rare and not always fatal cause of central pontine
      myelinolysis.

PMID- 28757178
TI  - Application of imaging techniques for Takayasu arteritis.
AB  - Arterial injury with subsequent remodelling and predisposition to arterial
      stenosis and/or dilation are the hallmarks of Takayasu arteritis. The degree of
      arterial damage closely aligns with prognosis and therefore its prevention is the
      predominant aim of therapy. Non-invasive imaging has greatly improved our ability
      to identify the extent and severity of disease and to monitor its progress.
      However, many questions remain concerning the optimal use of individual
      modalities at different stages of disease. Imaging methods for the quantification
      of arterial damage are lacking. Likewise, no single technique can accurately
      determine disease activity within the arterial wall or distinguish inflammatory
      and non-inflammatory disease progression. The aim of this review is to outline
      current imaging strategies in Takayasu arteritis, their individual roles in
      diagnosis and disease monitoring and potential future advances.

PMID- 28757180
TI  - Biocompatibility assessment of silk nanoparticles: hemocompatibility and
      internalization by human blood cells.
AB  - Many nanoparticles are designed for use as potential nanomedicines for parenteral
      administration. However, emerging evidence suggests that hemocompatibility is
      important, but is highly particle- and test-bed dependent. Thus, knowledge of
      bulk material properties does not predict the hemocompatibility of
      uncharacterized nanoparticles, including silk nanoparticles. This study compares
      the hemocompatibility of silk versus silica nanoparticles, using whole human
      blood under quasi-static and flow conditions. Substantial hemocompatibility
      differences are noted for some nanoparticles in quasi-static versus dynamic
      studies; i.e., the inflammatory response to silk nanoparticles is significantly
      lower under flow versus quasi-static conditions. Silk nanoparticles also have
      very low coagulant properties - an observation that scales from the macro- to the
      nano-level. These nanoparticle hemocompatibility studies are complemented by
      preliminary live cell measurements to evaluate the endocytosis and trafficking of
      nanoparticles in human blood cells. Overall, this study demonstrates that
      nanoparticle hemocompatibility is affected by several factors, including the test
      bed design.

PMID- 28757179
TI  - [Sclerosing epithelioid fibrosarcoma of the thorax associated with radioactive
      necklace].

PMID- 28757181
TI  - Tumor Organoids as a Pre-clinical Cancer Model for Drug Discovery.
AB  - Tumor organoids are 3D cultures of cancer cells that can be derived on an
      individual patient basis with a high success rate. This creates opportunities to
      build large biobanks with relevant patient material that can be used to perform
      drug screens and facilitate drug development. The high take rate will also allow
      side-by-side comparison to evaluate the translational potential of this model
      system to the patient. These tumors-in-a-dish can be established for a variety of
      tumor types including colorectal, pancreas, stomach, prostate, and breast
      cancers. In this review, we highlight what is currently known about tumor
      organoid culture, the advantages and challenges of the model system, compare it
      with other pre-clinical cancer models, and evaluate its value for drug
      development.

PMID- 28757183
TI  - Rapid Screening and Identification of Living Pathogenic Organisms via Optimized
      Bioorthogonal Non-canonical Amino Acid Tagging.
AB  - Pathogenic bacteria can be a major cause of illness from environmental sources as
      well as the consumption of contaminated products, giving rise to public health
      concerns globally. The surveillance of such living organisms in food and water
      supplies remains an important challenge in mitigating their deleterious societal
      effects. Here, we have developed an optimized bioorthogonal non-canonical amino
      acid tagging approach to the imaging, capture, and interrogation of
      shigatoxigenic/verotoxigenic Escherichia coli (VTEC) and Listeria that enables
      the distinction between living wild-type pathogenic bacteria. The approaches
      utilize homopropargylglycine (HPG), as well as optimized growth media, that
      restricts endogenous methionine biosynthesis in a variety of species of public
      health concern. Endogenous methionine residues are then replaced with HPG, which
      can then be modified using a myriad of compatible bioorthogonal reactions for
      tagging of exclusively live bacteria. The methods reported allow for the very
      rapid screening and identification of living pathogenic organisms.

PMID- 28757182
TI  - Amine Landscaping to Maximize Protein-Dye Fluorescence and Ultrastable Protein
      Ligand Interaction.
AB  - Chemical modification of proteins provides great opportunities to control and
      visualize living systems. The most common way to modify proteins is reaction of
      their abundant amines with N-hydroxysuccinimide (NHS) esters. Here we explore the
      impact of amine number and positioning on protein-conjugate behavior using
      streptavidin-biotin, a central research tool. Dye-NHS modification of
      streptavidin severely damaged ligand binding, necessitating development of a new
      streptavidin-retaining ultrastable binding after labeling. Exploring the ideal
      level of dye modification, we engineered a panel bearing 1-6 amines per subunit:
      "amine landscaping." Surprisingly, brightness increased as amine number
      decreased, revealing extensive quenching following conventional labeling. We
      ultimately selected Flavidin (fluorophore-friendly streptavidin), combining
      ultrastable ligand binding with increased brightness after conjugation. Flavidin
      enhanced fluorescent imaging, allowing more sensitive and specific cell labeling
      in tissues. Flavidin should have wide application in molecular detection,
      providing a general insight into how to optimize simultaneously the behavior of
      the biomolecule and the chemical probe.

PMID- 28757184
TI  - Cell Permeable Stapled Peptide Inhibitor of Wnt Signaling that Targets beta
      Catenin Protein-Protein Interactions.
AB  - The Wnt signaling pathway plays a critical role in cell proliferation and
      differentiation, thus it is often associated with diseases such as cancers.
      Unfortunately, although attractive, developing anti-cancer strategy targeting Wnt
      signaling has been challenging given that the most attractive targets are
      involved in protein-protein interactions (PPIs). Here, we develop a stapled
      peptide inhibitor that targets the interaction between beta-catenin and T cell
      factor/lymphoid enhancer-binding factor transcription factors, which are
      crucially involved in Wnt signaling. Our integrative approach combines peptide
      stapling to optimize proteolytic stability, with lessons learned from cell
      penetrating peptide (CPP) design to maximize cellular uptake resulting in NLS
      StAx-h, a selective, cell permeable, stapled peptide inhibitor of oncogenic Wnt
      signaling that efficiently inhibits beta-catenin-transcription factor
      interactions. We expect that this type of integrative strategy that endows
      stapled peptides with CPP features will be generally useful for developing
      inhibitors of intracellular PPIs.

PMID- 28757185
TI  - Effectiveness of Conducted Electrical Weapons to Prevent Violence-Related
      Injuries in the Hospital.
AB  - INTRODUCTION: Health care workers suffer higher rates of violence-related
      injuries than workers in other industries, with hospital security officers and ED
      personnel at particularly high risk for injury. Arming hospital security workers
      with conducted electrical weapons, such as tasers, has been suggested as an
      intervention to decrease violence-related injuries in the hospital. METHODS: A
      retrospective cohort of all security and ED nursing staff at an urban level 1
      trauma center was identified from human resources data for the period 4 years
      before and 7 years after security workers were armed with conducted electrical
      weapons. A violence-related rate of injury was calculated as all violence-related
      injuries incurred by each employee for the numerator and the productive hours
      worked by each person during the study period as the denominator. RESULTS: The
      hospital employed approximately 30 security staff and 200 nursing staff at the
      time, with a total of 98 security officers and 468 nursing staff members over the
      11 years of study. During the total nursing study period, 98 security officers
      contributed 452,901 hours; 265 registered nurses from the emergency department
      contributed 1,535,044 hours; and 203 health care assistants contributed 624,805
      hours. Security officers' violence-related rate of injury was 13 times higher
      than that of the nursing staff. The risk ratio was 1.0 (95% confidence interval
      [CI] 0.7-1.4) between the 2 examination periods for security officers, with
      similar results for nurses. However, among security workers, the cost of the
      injuries decreased in the period after implementation. CONCLUSION: Carrying
      conducted electrical weapons by hospital security staff appears to have limited
      capacity to decrease overall rates of violence-related injury but may decrease
      the severity of violence-related injuries. The latter could decease costs to
      health care organizations as well as morbidity of injured staff. Contribution to
      Emergency Nursing Practice.

PMID- 28757186
TI  - The basic reproduction number (R0) of measles: a systematic review.
AB  - The basic reproduction number, R nought (R0), is defined as the average number of
      secondary cases of an infectious disease arising from a typical case in a totally
      susceptible population, and can be estimated in populations if pre-existing
      immunity can be accounted for in the calculation. R0 determines the herd immunity
      threshold and therefore the immunisation coverage required to achieve elimination
      of an infectious disease. As R0 increases, higher immunisation coverage is
      required to achieve herd immunity. In July, 2010, a panel of experts convened by
      WHO concluded that measles can and should be eradicated. Despite the existence of
      an effective vaccine, regions have had varying success in measles control, in
      part because measles is one of the most contagious infections. For measles, R0 is
      often cited to be 12-18, which means that each person with measles would, on
      average, infect 12-18 other people in a totally susceptible population. We did a
      systematic review to find studies reporting rigorous estimates and determinants
      of measles R0. Studies were included if they were a primary source of R0,
      addressed pre-existing immunity, and accounted for pre-existing immunity in their
      calculation of R0. A search of key databases was done in January, 2015, and
      repeated in November, 2016, and yielded 10 883 unique citations. After screening
      for relevancy and quality, 18 studies met inclusion criteria, providing 58 R0
      estimates. We calculated median measles R0 values stratified by key covariates.
      We found that R0 estimates vary more than the often cited range of 12-18. Our
      results highlight the importance of countries calculating R0 using locally
      derived data or, if this is not possible, using parameter estimates from similar
      settings. Additional data and agreed review methods are needed to strengthen the
      evidence base for measles elimination modelling.

PMID- 28757187
TI  - Gout and risk of knee replacement for severe knee osteoarthritis in the Singapore
      Chinese Health Study.
AB  - OBJECTIVE: While cross-sectional and retrospective case-control studies suggest
      that gout is associated with knee osteoarthritis (KOA), no prospective study has
      evaluated the risk of total knee replacement (TKR) for KOA in association with
      gout. We prospectively evaluated the association between gout and the risk of TKR
      due to severe KOA. DESIGN: We used data from the Singapore Chinese Health Study
      (SCHS), a prospective cohort with 63,257 Chinese adults aged 45-74 years at
      recruitment (1993-1998). Self-report of physician-diagnosed gout was enquired at
      follow-up I interview (1999-2004) from 52,322 subjects. TKR cases for KOA after
      follow-up I were identified via linkage with nationwide hospital discharge
      database through 31 December 2011. Multivariable Cox proportional hazards
      regression model was applied with adjustment for potential risk factors of KOA.
      RESULTS: Among 51,858 subjects (22,180 men and 29,678 women) included in this
      analysis, after average 9.7 follow-up years, there were 1,435 cases of TKR. Gout
      was associated with 39% higher risk of TKR in women [hazard ratio (HR) 1.39; 95%
      confidence interval (CI) 1.08-1.79] but not in men (HR 0.78; 95% CI 0.49-1.23).
      The positive gout-TKR association in women remained after excluding participants
      with self-reported history of arthritis (HR 1.57; 95% CI 1.04-2.37). This
      association was stronger in women who were lean (body mass index [BMI] < 23
      kg/m2) (HR 2.17; 95% CI 1.30-3.64) compared to their heavier counterparts
      (Pinteraction = 0.016). CONCLUSION: Gout is associated with risk of severe KOA,
      especially in lean women, suggesting the crystal arthritis may play a role in the
      pathogenesis or progression of OA.

PMID- 28757188
TI  - A sex-specific association between incident radiographic osteoarthritis of hip or
      knee and incident peripheral arterial calcifications: 8-year prospective data
      from Cohort Hip and Cohort Knee (CHECK).
AB  - OBJECTIVES: There is sparse evidence for a relationship between cardiovascular
      disease (CVD) and osteoarthritis (OA). We investigated the association between
      incidence of arterial calcifications and incidence of radiographic knee and/or
      hip OA. DESIGN: We used baseline and 8-year follow-up data of Cohort Hip and
      Cohort Knee (CHECK). Knees and hips were either Kellgren-Lawrence (KL) grade 0 or
      1 at baseline. Arterial calcifications were scored on hip and knee radiographs
      using a four-grade scale. Scores were summed for patient-level analyses. To
      investigate incidence, participants with arterial calcifications at baseline or
      missing follow-up were excluded. Incident OA was defined per joint as KL >= 2 or
      prosthesis at year eight. The association between incidenct of arterial
      calcifications and incident OA was studied using mixed-effects logistic
      regression. RESULTS: Of 763 participants included, 623 (82%) were women. Mean
      (sd) age was 56 (5.1) years, mean (sd) body mass index (BMI) 26.2 (4.1) kg/m2.
      Arterial calcifications developed in 174 participants (283 joints). OA developed
      in 456 participants (778 joints). Sex modified the association between arterial
      calcification and OA. In women, incident arterial calcification around a joint
      was positively associated with incident OA in that joint (adjusted OR 2.51 (95%
      CI 1.57-4.03)). In men, no association was observed on joint-level, but at
      patient-level the arterial calcification sum score was negatively associated with
      incident OA (adjusted OR per point increase 0.70 (95% CI 0.54-0.90)) indicating a
      systemic effect. CONCLUSIONS: We observed sex-dependent associations between
      incident arterial calcification and incident radiographic knee and/or hip OA,
      which differs between joint- and patient-level.

PMID- 28757189
TI  - Natural products with anti-inflammatory and immunomodulatory activities against
      autoimmune myocarditis.
AB  - Myocarditis is an inflammatory disease of the myocardium associated with immune
      dysfunction which may frequently lead to the development of dilated
      cardiomyopathy. Experimental autoimmune myocarditis is an animal model which
      mimics myocarditis in order to allow assessment of the therapeutic effects of
      different molecules on this disease. We aimed to review the inflammatory and
      immunological mechanisms involved in the pathogenesis of the myocarditis and
      finding natural products and phytochemicals with anti-myocarditis activities
      based on studies of cardiac myosin-induced experimental autoimmune myocarditis in
      rodents. A number of natural molecules (e.g. apigenin, berberine and quercetin)
      along with some plant extracts were found to be effective in alleviating
      experimental autoimmune myocarditis. Upregulation of Th1-type cytokines and
      elevation of the Th2-type cytokines (IL-4 and IL-10), mitigation of oxidative
      stress, modulation of mitogen-activated protein kinase signaling pathways and
      increasing Sarco-endoplasmic reticulum Ca2+-ATPase levels are among the most
      important anti-myocarditis mechanisms for the retrieved molecules and extracts.
      Interestingly, there are structural similarities between the anti-EAM compounds,
      suggesting the presence of similar pharmacophore and enzymatic targets for these
      molecules. Naturally occurring molecules discussed in the present article are
      potential anti-myocarditis drugs and future additional animal studies and
      clinical trials would shed more light on their effectiveness in the treatment of
      myocarditis and prevention of dilated cardiomyopathy.

PMID- 28757190
TI  - [Severe diarrhoea due to autoimmune enteropathy: Treatment and outcomes].

PMID- 28757191
TI  - [Acute torticollis on awakening in an infant].

PMID- 28757192
TI  - Delivery of epidermal growth factor receptor inhibitor via a customized collagen
      scaffold promotes meniscal defect regeneration in a rabbit model.
AB  - : Meniscal injury is one of the most common knee joint injuries, which remains an
      intractable challenge in clinical practice to date. Aberrant epidermal growth
      factor receptor (EGFR) activation levels in both human and mice menisci following
      injury, prompted us to investigate the functional role of EGFR by utilizing an
      inducible cartilage-specific EGFR-deficient mouse model. We demonstrated that
      conditional EGFR deletion in mice resulted in increased partial meniscectomy
      induced ECM production within the meniscus, which is comparable to utilization of
      the small molecule EGFR inhibitor, gefitinib, to block EGFR activity. Here, we
      combined intra-articular delivery of gefitinib with an implanted customized
      collagen scaffold to substitute for lost meniscal tissue, as well as to promote
      meniscal regeneration and prevent osteoarthritis (OA) progression in a rabbit
      meniscectomy model. STATEMENT OF SIGNIFICANCE: The main novelty of this study is
      the finding of a new application for small molecule EGFR inhibitor in meniscal
      injury therapy. This study also highlights the importance of using a customized
      collagen scaffold to provide robust mechanical strength and effectively promote
      meniscus regeneration. In summary, our study finds that intra-articular delivery
      of gefitinib together with implantation of a customized, multi-layer collagen
      scaffold not only enhanced meniscal regeneration, but also protected articular
      cartilage from degeneration in rabbit model. These results provide valuable
      insight for meniscal tissue engineering studies and clinical practice.

PMID- 28757193
TI  - Normalization of cortical thickness measurements across different T1 magnetic
      resonance imaging protocols by novel W-Score standardization.
AB  - BACKGROUND: The use of different 3D T1-weighted magnetic resonance (T1 MR)
      imaging protocols induces image incompatibility across multicenter studies,
      negating the many advantages of multicenter studies. A few methods have been
      developed to address this problem, but significant image incompatibility still
      remains. Thus, we developed a novel and convenient method to improve image
      compatibility. METHODS: W-score standardization creates quality reference values
      by using a healthy group to obtain normalized disease values. We developed a
      protocol-specific w-score standardization to control the protocol effect, which
      is applied to each protocol separately. We used three data sets. In dataset 1,
      brain T1 MR images of normal controls (NC) and patients with Alzheimer's disease
      (AD) from two centers, acquired with different T1 MR protocols, were used
      (Protocol 1 and 2, n = 45/group). In dataset 2, data from six subjects, who
      underwent MRI with two different protocols (Protocol 1 and 2), were used with
      different repetition times, echo times, and slice thicknesses. In dataset 3, T1
      MR images from a large number of healthy normal controls (Protocol 1: n = 148,
      Protocol 2: n = 343) were collected for w-score standardization. The protocol
      effect and disease effect on subjects' cortical thickness were analyzed before
      and after the application of protocol-specific w-score standardization. RESULTS:
      As expected, different protocols resulted in differing cortical thickness
      measurements in both NC and AD subjects. Different measurements were obtained for
      the same subject when imaged with different protocols. Multivariate pattern
      difference between measurements was observed between the protocols.
      Classification accuracy between two protocols was nearly 90%. After applying
      protocol-specific w-score standardization, the differences between the protocols
      substantially decreased. Most importantly, protocol-specific w-score
      standardization reduced both univariate and multivariate differences in the
      images while maintaining the AD disease effect. Compared to conventional
      regression methods, our method showed the best performance for in terms of
      controlling the protocol effect while preserving disease information.
      CONCLUSIONS: Protocol-specific w-score standardization effectively resolved the
      concerns of conventional regression methods. It showed the best performance for
      improving the compatibility of a T1 MR post-processed feature, cortical
      thickness.

PMID- 28757194
TI  - Time-resolved phase-amplitude coupling in neural oscillations.
AB  - Cross-frequency coupling between neural oscillations is a phenomenon observed
      across spatial scales in a wide range of preparations, including human non
      invasive electrophysiology. Although the functional role and mechanisms involved
      are not entirely understood, the concept of interdependent neural oscillations
      drives an active field of research to comprehend the ubiquitous polyrhythmic
      activity of the brain, beyond empirical observations. Phase-amplitude coupling, a
      particular form of cross-frequency coupling between bursts of high-frequency
      oscillations and the phase of lower frequency rhythms, has recently received
      considerable attention. However, the measurement methods have relatively poor
      sensitivity and require long segments of experimental data. This obliterates the
      resolution of fast changes in coupling related to behavior, and more generally,
      to the non-stationary dynamics of brain electrophysiology. We propose a new
      measure of phase-amplitude coupling that can resolve up to one, optimally two,
      cycles of the underlying slow frequency component. The method also provides a
      measure of the coupling strength, for augmented insight into the mechanisms
      involved. We demonstrate the technique with synthesized data and compare its
      performances with existing methods. We also show that the method reveals rapid
      changes in coupling parameters in data from the entorhinal cortex of a free
      behaving rat. The time-resolved changes revealed are compatible with behavior and
      complement observed modulations of oscillatory power. We anticipate that this new
      measure of dynamic phase-amplitude coupling will contribute to accelerate
      research into the dynamics of inter-dependent oscillatory components related to
      brain functions and dysfunctions.

PMID- 28757196
TI  - Air pollution and its relationship to lung function among adolescents from
      Taubate, Sao Paulo, Brazil.
AB  - BACKGROUND: This paper sought to evaluate individual exposure to air pollution by
      quantifying the carbon in alveolar macrophages (AMs) and its relationship to lung
      function. We also examined the proximity of participants' residences to the
      Presidente Dutra highway (PDH) in adolescents with asthma from Taubate, Sao
      Paulo, Brazil. METHODS: This descriptive study examined fifty 13- to 14-year-old
      adolescents with asthma identified by the International Study of Asthma and
      Allergies in Childhood (ISAAC) in Taubate. These adolescents underwent spirometry
      and sputum induction via the inhalation of 3% hypertonic saline (HSS). Sputum was
      collected after each nebulisation, and forced expiratory flow in one second
      (FEV1) was measured. The collected sputum was stored and transported to the
      laboratory; it was then processed and analysed for ultrafine particles (<=100nm).
      This analysis was correlated with the residence location and FEV1 of each
      adolescent. RESULTS: A total of 39 adolescents completed the study. The
      comparison of the carbon fraction within macrophages (CA/MA) showed no
      differences according to residence in relation to the PDH (p=0.758). After
      adjustment, a mixed linear model with FEV1 as the dependent variable and CA/MA,
      location, and evaluation condition as the predictors found that the interactions
      among the variables were not significant. CONCLUSIONS: The amount of carbon
      present within the AMs of adolescents with asthma was not correlated with either
      lung function or residence location. Evaluations of the topography and local
      climatic conditions in Taubate should be considered in future studies.

PMID- 28757195
TI  - Selective entrainment of brain oscillations drives auditory perceptual
      organization.
AB  - Perceptual sound organization supports our ability to make sense of the complex
      acoustic environment, to understand speech and to enjoy music. However, the
      neuronal mechanisms underlying the subjective experience of perceiving univocal
      auditory patterns that can be listened to, despite hearing all sounds in a scene,
      are poorly understood. We hereby investigated the manner in which competing sound
      organizations are simultaneously represented by specific brain activity patterns
      and the way attention and task demands prime the internal model generating the
      current percept. Using a selective attention task on ambiguous auditory
      stimulation coupled with EEG recordings, we found that the phase of low-frequency
      oscillatory activity dynamically tracks multiple sound organizations
      concurrently. However, whereas the representation of ignored sound patterns is
      circumscribed to auditory regions, large-scale oscillatory entrainment in
      auditory, sensory-motor and executive-control network areas reflects the active
      perceptual organization, thereby giving rise to the subjective experience of a
      unitary percept.

PMID- 28757197
TI  - Correlation between serum vitamin D status and immunological changes in children
      affected by gastrointestinal food allergy.
AB  - BACKGROUND: Low vitamin D status is linked to increased incidence of food allergy
      and intestinal inflammation. Whether vitamin D status is associated with
      immunological changes in children with gastrointestinal food allergy (GFA)
      remains unclear. METHODS: Forty-nine GFA children (aged 2-11 years old) were
      enrolled in this study. Serum 25-hydroxyvitamin D (25OHD) level, total
      immunoglobulin E (IgE), specific IgE against allergens, circulating regulatory T
      lymphocytes (Tregs), and blood eosinophil numbers were measured. RESULTS: Levels
      of serum 25OHD in the GFA children ranged 35.5-156.4nmol/L, with a mean value
      similar to that of the healthy controls. Compared to those with normal 25OHD
      (>=75nmol/L), GFA children with low 25OHD (<75nmol/L) had increased total IgE
      (84% vs. 54%, P<0.05), persistent blood eosinophilia (56% vs. 25%, P<0.05), and
      delayed resolution of symptoms after food allergen elimination (odds ratio 3.51,
      95% CI 1.00-12.36, P<0.05). Among the GFA children with elevated total IgE, those
      with low 25OHD had lower circulatory Tregs (8.79+/-2.4% vs. 10.21+/-1.37%,
      P<0.05), higher total IgE (1197.5+/-1209.8 vs. 418.5+/-304.6kU/L, P<0.05), and
      persistent eosinophilia (0.61+/-0.52 vs. 0.31+/-0.15*109cells/L, P<0.05) compared
      to those with normal 25OHD. In addition, serum 25OHD concentrations inversely
      correlated with total IgE (R=-0.434, P<0.05), and positively with Treg population
      (R=0.356, P<0.05). CONCLUSION: Low serum vitamin D status correlates with
      stronger allergic immune response in GFA children.

PMID- 28757198
TI  - Dissecting the immune pathways stimulated following injection vaccination of
      rainbow trout (Oncorhynchus mykiss) against enteric redmouth disease (ERM).
AB  - Enteric redmouth disease (ERM or yersiniosis) is one of the most important
      diseases of salmonids and leads to significant economic losses. It is caused by
      the Gram-negative bacterium Yersinia ruckeri but can be controlled by bacterin
      vaccination. The first commercial ERM vaccine was licenced in 1976 and is one of
      the most significant and successful health practices within the aquaculture
      industry. Although ERM vaccination provides complete protection, knowledge of the
      host immune response to the vaccine and the molecular mechanisms that underpin
      the protection elicited is limited. In this report, we analysed the expression in
      spleen and gills of a large set of genes encoding for cytokines, acute phase
      proteins (APPs) and antimicrobial peptides (AMPs) in response to ERM vaccination
      in rainbow trout, Oncorhynchus mykiss. Many immune genes in teleost fish are
      known to have multiple paralogues that can show differential responses to ERM
      vaccination, highlighting the necessity to determine whether all of the genes
      present react in a similar manner. ERM vaccination immediately activated a
      balanced inflammatory response with correlated expression of both pro- and anti
      inflammatory cytokines (eg IL-1beta1-2, TNF-alpha1-3, IL-6, IL-8 and IL-10A etc.)
      in the spleen. The increase of pro-inflammatory cytokines may explain the
      systemic upregulation of APPs (eg serum amyloid A protein and serum amyloid
      protein P) and AMPs (eg cathelicidins and hepcidin) seen in both spleen and
      gills. We also observed an upregulation of all the alpha-chains but only one beta
      chain (p40B2) of the IL-12 family cytokines, that suggests specific IL-12 and IL
      23 isoforms with distinct functions might be produced in the spleen of vaccinated
      fish. Notably the expression of Th1 cytokines (IFN-gamma1-2) and a Th17 cytokine
      (IL-17A/F1a) was also up-regulated and correlated with enhanced expression of the
      IL-12 family alpha-chains, and the majority of pro- and anti-inflammatory
      cytokines, APPs and AMPs. These expression profiles may suggest that ERM
      vaccination activates host innate immunity and expression of specific IL-12 and
      IL-23 isoforms leading to a Th1 and Th17 biased immune response. A late induction
      of Th2 cytokines (IL-4/13B1-2) was also observed, that may have a homeostatic
      role and/or involvement in antibody production. This study has increased our
      understanding of the host immune response to ERM vaccination and the adaptive
      pathways involved. The early responses of a set of genes established in this
      study may provide essential information and function as biomarkers in future
      vaccine development in aquaculture.

PMID- 28757199
TI  - Comparative transcriptome analysis of zebrafish (Danio rerio) brain and spleen
      infected with spring viremia of carp virus (SVCV).
AB  - Spring viremia of carp virus (SVCV) is the pathogen of spring viremia of carp
      (SVC) and often causes acute hemorrhagic symptoms in various kinds of cyprinids
      and induces serious environmental and economic losses. However, the molecular
      mechanisms of infection remain poorly understood, especially at the individual
      level. In this study, zebrafish was employed as the infection model to explore
      the pathogenesis of SVCV. 4 groups of zebrafish tissues were set and RNA
      sequencing (RNA-Seq) technology was employed to analyze the differentially
      expressed genes (DEGs) after SVCV-infection. A total of 360,971,498 clean reads
      were obtained from 12 samples, 382 DEGs in the brain and 926 DEGs in the spleen
      were identified. These DEGs were annotated into three ontologies after gene
      ontology (GO) enrichment analysis. The Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathway analysis showed that these DEGs were primarily related to
      Influenza A pathway and Herpes simplex infection pathway in brain and
      Tuberculosis and Toxoplasmosis pathways in spleen, and all of these pathways may
      be involved in response to pathogen invasion. At the same time, 3' and 5'
      alternative splicing (AS) events were significantly up-regulated in the spleen.
      The transcriptome analysis results demonstrated changes and tissue-specific
      influences caused by SVCV in vivo, which provided us with more information to
      understand the complex relationships between SVCV and its host.

PMID- 28757200
TI  - Silver nanoparticles enhance wound healing in zebrafish (Danio rerio).
AB  - Silver nanoparticles (AgNPs) were successfully synthesized by a chemical
      reduction method, physico-chemically characterized and their effect on wound
      healing activity in zebrafish was investigated. The prepared AgNPs were circular
      shaped, water soluble with average diameter and zeta potential of 72.66 nm and 
      0.45 mv, respectively. Following the creation of a laser skin wound on zebrafish,
      the effect of AgNPs on wound-healing activity was tested by two methods, direct
      skin application (2 MUg/wound) and immersion in a solution of AgNPs and water (50
      MUg/L). The zebrafish were followed for 20 days post-wounding (dpw) by visual
      observation of wound size, calculating wound healing percentage (WHP), and
      histological examination. Visually, both direct skin application and immersion
      AgNPs treatments displayed clear and faster wound closure at 5, 10 and 20 dpw
      compared to the controls, which was confirmed by 5 dpw histology data. At 5 dpw,
      WHP was highest in the AgNPs immersion group (36.6%) > AgNPs direct application
      group (23.7%) > controls (18.2%), showing that WHP was most effective in fish
      immersed in AgNPs solution. In general, exposure to AgNPs induced gene expression
      of selected wound-healing-related genes, namely, transforming growth factor (TGF
      beta), matrix metalloproteinase (MMP) -9 and -13, pro-inflammatory cytokines (IL
      1beta and TNF-alpha) and antioxidant enzymes (superoxide dismutase and catalase),
      which observed differentiation at 12 and 24 h against the control; but the
      results were not consistently significant, and many either reached basal levels
      or were down regulated at 5 dpw in the wounded muscle. These results suggest that
      AgNPs are effective in acceleration of wound healing and altered the expression
      of some wound-healing-related genes. However, the detailed mechanism of enhanced
      wound healing remains to be investigated in fish.

PMID- 28757201
TI  - Continuity and Admixture in the Last Five Millennia of Levantine History from
      Ancient Canaanite and Present-Day Lebanese Genome Sequences.
AB  - The Canaanites inhabited the Levant region during the Bronze Age and established
      a culture that became influential in the Near East and beyond. However, the
      Canaanites, unlike most other ancient Near Easterners of this period, left few
      surviving textual records and thus their origin and relationship to ancient and
      present-day populations remain unclear. In this study, we sequenced five whole
      genomes from ~3,700-year-old individuals from the city of Sidon, a major
      Canaanite city-state on the Eastern Mediterranean coast. We also sequenced the
      genomes of 99 individuals from present-day Lebanon to catalog modern Levantine
      genetic diversity. We find that a Bronze Age Canaanite-related ancestry was
      widespread in the region, shared among urban populations inhabiting the coast
      (Sidon) and inland populations (Jordan) who likely lived in farming societies or
      were pastoral nomads. This Canaanite-related ancestry derived from mixture
      between local Neolithic populations and eastern migrants genetically related to
      Chalcolithic Iranians. We estimate, using linkage-disequilibrium decay patterns,
      that admixture occurred 6,600-3,550 years ago, coinciding with recorded massive
      population movements in Mesopotamia during the mid-Holocene. We show that present
      day Lebanese derive most of their ancestry from a Canaanite-related population,
      which therefore implies substantial genetic continuity in the Levant since at
      least the Bronze Age. In addition, we find Eurasian ancestry in the Lebanese not
      present in Bronze Age or earlier Levantines. We estimate that this Eurasian
      ancestry arrived in the Levant around 3,750-2,170 years ago during a period of
      successive conquests by distant populations.

PMID- 28757202
TI  - Leveraging Multi-ethnic Evidence for Risk Assessment of Quantitative Traits in
      Minority Populations.
AB  - An essential component of precision medicine is the ability to predict an
      individual's risk of disease based on genetic and non-genetic factors. For
      complex traits and diseases, assessing the risk due to genetic factors is
      challenging because it requires knowledge of both the identity of variants that
      influence the trait and their corresponding allelic effects. Although the set of
      risk variants and their allelic effects may vary between populations, a large
      proportion of these variants were identified based on studies in populations of
      European descent. Heterogeneity in genetic architecture underlying complex traits
      and diseases, while broadly acknowledged, remains poorly characterized. Ignoring
      such heterogeneity likely reduces predictive accuracy for minority individuals.
      In this study, we propose an approach, called XP-BLUP, which ameliorates this
      ethnic disparity by combining trans-ethnic and ethnic-specific information. We
      build a polygenic model for complex traits that distinguishes candidate trait
      relevant variants from the rest of the genome. The set of candidate variants are
      selected based on studies in any human population, yet the allelic effects are
      evaluated in a population-specific fashion. Simulation studies and real data
      analyses demonstrate that XP-BLUP adaptively utilizes trans-ethnic information
      and can substantially improve predictive accuracy in minority populations. At the
      same time, our study highlights the importance of the continued expansion of
      minority cohorts.

PMID- 28757203
TI  - Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated
      with Severe Neonatal Encephalopathy.
AB  - Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2
      oxoacid dehydrogenases functioning in energy metabolism (alpha-oxoglutarate
      dehydrogenase [alpha-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid
      metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase).
      Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed
      sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase
      (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated
      with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy
      combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency
      spares GCS deficiency and has been associated with a biochemical signature of
      combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like
      encephalopathy. We report on the identification of biallelic LIPT2 mutations in
      three affected individuals from two families with severe neonatal encephalopathy.
      Brain MRI showed major cortical atrophy with white matter abnormalities and
      cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts
      showed reduced oxygen consumption rates, PDHc, alpha-KGDHc activities, leucine
      catabolic flux, and decreased protein lipoylation. A normalization of lipoylation
      was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement
      in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not
      improve clinical condition nor activities of PDHc, alpha-KGDHc, or leucine
      metabolism in fibroblasts and was ineffective in yeast deleted for the
      orthologous LIP2.

PMID- 28757205
TI  - Genetic disorders of bone - An historical perspective.

PMID- 28757206
TI  - Nitric Oxide Regulates Protein Methylation during Stress Responses in Plants.
AB  - Methylation and nitric oxide (NO)-based S-nitrosylation are highly conserved
      protein posttranslational modifications that regulate diverse biological
      processes. In higher eukaryotes, PRMT5 catalyzes Arg symmetric dimethylation,
      including key components of the spliceosome. The Arabidopsis prmt5 mutant shows
      severe developmental defects and impaired stress responses. However, little is
      known about the mechanisms regulating the PRMT5 activity. Here, we report that NO
      positively regulates the PRMT5 activity through S-nitrosylation at Cys-125 during
      stress responses. In prmt5-1 plants, a PRMT5C125S transgene, carrying a non
      nitrosylatable mutation at Cys-125, fully rescues the developmental defects, but
      not the stress hypersensitive phenotype and the responsiveness to NO during
      stress responses. Moreover, the salt-induced Arg symmetric dimethylation is
      abolished in PRMT5C125S/prmt5-1 plants, correlated to aberrant splicing of pre
      mRNA derived from a stress-related gene. These findings define a mechanism by
      which plants transduce stress-triggered NO signal to protein methylation
      machinery through S-nitrosylation of PRMT5 in response to environmental
      alterations.

PMID- 28757204
TI  - Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin
      D Levels and Risk of Multiple Sclerosis.
AB  - Vitamin D insufficiency is common, correctable, and influenced by genetic
      factors, and it has been associated with risk of several diseases. We sought to
      identify low-frequency genetic variants that strongly increase the risk of
      vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a
      disease influenced by low vitamin D concentrations. We used whole-genome
      sequencing data from 2,619 individuals through the UK10K program and deep
      imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of
      the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency
      (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A
      (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25
      hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed
      25OHD per A allele; p value = 1.5 * 10-88). The effect on 25OHD was four times
      larger and independent of the effect of a previously described common variant
      near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers
      of this low-frequency variant have an increased risk of vitamin D insufficiency
      (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 * 10
      12). Individuals carrying one copy of this variant also had increased odds of
      multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 * 10-5) in a sample of
      5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency
      CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified
      to date in the general European population and implicates vitamin D in the
      etiology of multiple sclerosis.

PMID- 28757207
TI  - Focal Adhesion- and IGF1R-Dependent Survival and Migratory Pathways Mediate Tumor
      Resistance to mTORC1/2 Inhibition.
AB  - Aberrant signaling by the mammalian target of rapamycin (mTOR) contributes to the
      devastating features of cancer cells. Thus, mTOR is a critical therapeutic target
      and catalytic inhibitors are being investigated as anti-cancer drugs. Although
      mTOR inhibitors initially block cell proliferation, cell viability and migration
      in some cancer cells are quickly restored. Despite sustained inhibition of
      mTORC1/2 signaling, Akt, a kinase regulating cell survival and migration, regains
      phosphorylation at its regulatory sites. Mechanistically, mTORC1/2 inhibition
      promotes reorganization of integrin/focal adhesion kinase-mediated adhesomes,
      induction of IGFR/IR-dependent PI3K activation, and Akt phosphorylation via an
      integrin/FAK/IGFR-dependent process. This resistance mechanism contributes to
      xenograft tumor cell growth, which is prevented with mTOR plus IGFR inhibitors,
      supporting this combination as a therapeutic approach for cancers.

PMID- 28757208
TI  - Vps34 Kinase Domain Dynamics Regulate the Autophagic PI 3-Kinase Complex.
AB  - The class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) is required for
      the initiation of essentially all macroautophagic processes. PI3KC3-C1 consists
      of the lipid kinase catalytic subunit VPS34, the VPS15 scaffold, and the
      regulatory BECN1 and ATG14 subunits. The VPS34 catalytic domain and BECN1:ATG14
      subcomplex do not touch, and it is unclear how allosteric signals are transmitted
      to VPS34. We used EM and crosslinking mass spectrometry to dissect five
      conformational substates of the complex, including one in which the VPS34
      catalytic domain is dislodged from the complex but remains tethered by an
      intrinsically disordered linker. A "leashed" construct prevented dislodging
      without interfering with the other conformations, blocked enzyme activity in
      vitro, and blocked autophagy induction in yeast cells. This pinpoints the
      dislodging and tethering of the VPS34 catalytic domain, and its regulation by
      VPS15, as a master allosteric switch in autophagy induction.

PMID- 28757210
TI  - Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic
      Instability.
AB  - Transcription is a source of genetic instability that can notably result from the
      formation of genotoxic DNA:RNA hybrids, or R-loops, between the nascent mRNA and
      its template. Here we report an unexpected function for introns in counteracting
      R-loop accumulation in eukaryotic genomes. Deletion of endogenous introns
      increases R-loop formation, while insertion of an intron into an intronless gene
      suppresses R-loop accumulation and its deleterious impact on transcription and
      recombination in yeast. Recruitment of the spliceosome onto the mRNA, but not
      splicing per se, is shown to be critical to attenuate R-loop formation and
      transcription-associated genetic instability. Genome-wide analyses in a number of
      distant species differing in their intron content, including human, further
      revealed that intron-containing genes and the intron-richest genomes are best
      protected against R-loop accumulation and subsequent genetic instability. Our
      results thereby provide a possible rationale for the conservation of introns
      throughout the eukaryotic lineage.

PMID- 28757209
TI  - Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent
      DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments.
AB  - Brca2 deficiency causes Mre11-dependent degradation of nascent DNA at stalled
      forks, leading to cell lethality. To understand the molecular mechanisms
      underlying this process, we isolated Xenopus laevis Brca2. We demonstrated that
      Brca2 protein prevents single-stranded DNA gap accumulation at replication fork
      junctions and behind them by promoting Rad51 binding to replicating DNA. Without
      Brca2, forks with persistent gaps are converted by Smarcal1 into reversed forks,
      triggering extensive Mre11-dependent nascent DNA degradation. Stable Rad51
      nucleofilaments, but not RPA or Rad51T131P mutant proteins, directly prevent
      Mre11-dependent DNA degradation. Mre11 inhibition instead promotes reversed fork
      accumulation in the absence of Brca2. Rad51 directly interacts with the Pol alpha
      N-terminal domain, promoting Pol alpha and delta binding to stalled replication
      forks. This interaction likely promotes replication fork restart and gap
      avoidance. These results indicate that Brca2 and Rad51 prevent formation of
      abnormal DNA replication intermediates, whose processing by Smarcal1 and Mre11
      predisposes to genome instability.

PMID- 28757212
TI  - Bradykinin B2 and dopamine D2 receptors form a functional dimer.
AB  - In recent years a wide range of studies have shown that G protein-coupled
      receptors modulate a variety of cell functions through the formation of dimers.
      For instance, there is growing evidence for the dimerization of bradykinin or
      dopamine receptors, both as homodimers and heterodimers. A discovery of direct
      interactions of angiotensin II receptors with bradykinin 2 receptor (B2R) or
      dopamine D2 (D2R) receptor has led to a hypothesis on a potential dimerization
      between two latter receptors. In this study, we have demonstrated a constitutive
      colocalization of receptors on the membranes of HEK293 cells transiently
      transfected with plasmid vectors encoding B2R and D2R, fused with fluorescent
      proteins. The receptor colocalization was significantly enhanced by specific
      agonists of B2R or D2R after 5min following the addition, whereas simultaneous
      stimulation with these agonists did not influence the B2R/D2R colocalization
      level. In addition, B2R-D2R heterodimerization was confirmed with FLIM-FRET
      technique. The most characteristic signaling pathways for B2R and D2R, dependent
      on intracellular Ca2+ and cAMP concentration, respectively, were analyzed in
      cells presenting similar endogenous expression of B2R and D2R. Significant
      changes in receptors' signaling were observed after simultaneous stimulation with
      agonists, suggesting transformations in proteins' conformation after
      dimerization. The evidence of B2R-D2R dimerization may open new perspectives in
      the modulation of diverse cellular functions which depend on their activation.

PMID- 28757211
TI  - AID Recognizes Structured DNA for Class Switch Recombination.
AB  - Activation-induced cytidine deaminase (AID) initiates both class switch
      recombination (CSR) and somatic hypermutation (SHM) in antibody diversification.
      Mechanisms of AID targeting and catalysis remain elusive despite its critical
      immunological roles and off-target effects in tumorigenesis. Here, we produced
      active human AID and revealed its preferred recognition and deamination of
      structured substrates. G-quadruplex (G4)-containing substrates mimicking the
      mammalian immunoglobulin switch regions are particularly good AID substrates in
      vitro. By solving crystal structures of maltose binding protein (MBP)-fused AID
      alone and in complex with deoxycytidine monophosphate, we surprisingly identify a
      bifurcated substrate-binding surface that explains structured substrate
      recognition by capturing two adjacent single-stranded overhangs simultaneously.
      Moreover, G4 substrates induce cooperative AID oligomerization. Structure-based
      mutations that disrupt bifurcated substrate recognition or oligomerization both
      compromise CSR in splenic B cells. Collectively, our data implicate intrinsic
      preference of AID for structured substrates and uncover the importance of G4
      recognition and oligomerization of AID in CSR.

PMID- 28757213
TI  - Oxidative stress parameters in two Pelophylax esculentus complex frogs during pre
      and post-hibernation: Arousal vs heavy metals.
AB  - In spring, frogs from temperate regions are faced with arousal-induced oxidative
      stress and exposure to various xenobiotics from the environment. The question is
      whether pollutants can significantly modify the antioxidative defense system
      (AOS) response of hibernators during recovery from hibernation. If this
      assumption is true, we would then expect different patterns of seasonal
      variations in the AOS between individuals exposed to different levels of
      pollution. To examine this assumption, we determined the relationship between
      seasonal variations of accumulated metals and AOS parameters in the skin and
      muscle of two frog species from the Pelophylax esculentus complex (P. ridibundus
      and P. esculentus) inhabiting two localities (the Danube-Tisza-Danube canal and
      the Ponjavica River) with different levels of pollution during pre- and post
      hibernation periods, respectively autumn and spring. Our results showed that even
      though there were differences in the concentrations of accumulated metals and AOS
      parameters between localities and species, the frogs displayed almost the same
      patterns of AOS variations during seasons, with a higher AOS response observed in
      spring. The parameters SH groups, GSH, GR and SOD had been contributed most
      rather than others. Our findings indicate that oxidative stress during the post
      hibernation period was mainly caused by the organisms' recovery from hibernation,
      as the result of natural selection acting on the AOS, and that the accumulated
      metals did not significantly modify the AOS response. The present study provides
      new insight into the biological and physiological cellular responses of frogs to
      arousal stress.

PMID- 28757214
TI  - Vulnerability of marsh frog Pelophylax ridibundus to the typical wastewater
      effluents ibuprofen, triclosan and estrone, detected by multi-biomarker approach.
AB  - Pharmaceutical and personal care products (PPCPs) are the environmental
      pollutants of growing concern. The aim of this study was to indicate the effects
      of typical PPCPs on the marsh frog Pelophylax ridibundus. We treated male frogs
      with waterborne ibuprofen (IBU, 250ng.L-1), triclosan (TCS, 500ng.L-1), or
      estrone (E1, 100ng.L-1) for 14days. Common vulnerability of the frogs was
      detected from dramatic decrease of Zn, total and metalated metallothionein (MT)
      concentrations, Zn/Cu ratio, the elevation of activity of glutathione-S
      transferase, cathepsin D and DNA instability in the liver, the depletion of
      cholinesterase in the brain and cortisol in the blood plasma in all exposures.
      Nevertheless, lipofuscin concentration in the liver was always decreased. The
      groups were best distinguished by cytochrome P450 (CYP450) activity determined by
      ELISA. The exposure to IBU caused lesser damage, but elevated the levels of
      oxyradicals and glutathione (GSH and GSSG) and lysosomal membrane instability.
      Exposures to TCS and E1 provoked the endocrine disturbance (increased levels of
      vitellogenin and thyrotropin in blood plasma), decreased lactate dehydrogenase
      activity and increased level of pyruvate in the liver. TCS caused the increase of
      GSSG by 7.3 times and lactate levels. Only E1 lead to decrease of deiodinase
      activity in the liver, activation of CYP450 and caspase-3 and efflux of cathepsin
      D from lysosomes. Spectrophotometric and ELISA assays of MTs and CYP450 gave
      distinct results in E1-group. Broad disruption of the hormonal pathways caused by
      E1 could be of concern for the health status of frogs in their habitats.

PMID- 28757215
TI  - Catch a tiger snake by its tail: Differential toxicity, co-factor dependence and
      antivenom efficacy in a procoagulant clade of Australian venomous snakes.
AB  - A paradigm of venom research is adaptive evolution of toxins as part of a
      predator-prey chemical arms race. This study examined differential co-factor
      dependence, variations relative to dietary preference, and the impact upon
      relative neutralisation by antivenom of the procoagulant toxins in the venoms of
      a clade of Australian snakes. All genera were characterised by venoms rich in
      factor Xa which act upon endogenous prothrombin. Examination of toxin sequences
      revealed an extraordinary level of conservation, which indicates that adaptive
      evolution is not a feature of this toxin type. Consistent with this, the venoms
      did not display differences on the plasma of different taxa. Examination of the
      prothrombin target revealed endogenous blood proteins are under extreme negative
      selection pressure for diversification, this in turn puts a strong negative
      selection pressure upon the toxins as sequence diversification could result in a
      drift away from the target. Thus this study reveals that adaptive evolution is
      not a consistent feature in toxin evolution in cases where the target is under
      negative selection pressure for diversification. Consistent with this high level
      of toxin conservation, the antivenom showed extremely high-levels of cross
      reactivity. There was however a strong statistical correlation between relative
      degree of phospholipid-dependence and clotting time, with the least dependent
      venoms producing faster clotting times than the other venoms even in the presence
      of phospholipid. The results of this study are not only of interest to
      evolutionary and ecological disciplines, but also have implications for clinical
      toxinology.

PMID- 28757216
TI  - Epidural catheter anchored in the posterior lateral epidural space: How to manage
      it.
AB  - We describe a case of an epidural catheter entrapment without knotting, kinking,
      shearing or breakage confirmed by CT scan and how to manage it. A patient was
      admitted for tibial fracture repair under general anesthesia with an epidural. At
      discharge day, multiple attempts to retrieve the catheter were made. Contrast CT
      scan showed the catheter anchored in the left posterior-lateral epidural space.
      Despite the absence of guidelines regarding epidural catheter entrapment, all the
      methods described in the literature were used. This is a rare complication and it
      may be associated with neurological and infectious complications. Radiologic
      imaging should be obtained to better characterize the catheters' position and
      plan removal. In this case, tension in the paraspinal muscles or in the
      supraspinous and intraspinous ligaments could explain the entrapment. General
      anesthesia with the non-depolarising muscle relaxant allowed muscles and
      ligaments to relax and we were able to retrieve the catheter intact.

PMID- 28757217
TI  - Simulation of rain enhances horizontal transmission of the microsporidium Nosema
      lymantriae via infective feces.
AB  - Larvae of the gypsy moth, Lymantria dispar, infected with the microsporidium,
      Nosema lymantriae, release infective spores with feces. We tested the effects of
      simulated light rain on transmission in cages, providing random contamination of
      host plant foliage with feces. Contamination by larvae in the intermediate stage
      of infection, 15-16days post inoculation, entailed transmission to a mean 4.4
      16.7% of test larvae. Simulated rain significantly increased transmission to 30.0
      57.3%. Transmission success significantly increased with disease progress.
      Experiments demonstrated that feces are a suitable source of spores and a likely
      transmission pathway in the field.

PMID- 28757218
TI  - The new norms of food waste at the curb: Evidence-based policy tools to address
      benefits and barriers.
AB  - Cities around the world are under increasing political pressure to develop
      organics collection programs (OCP) to curb the flow of food waste into landfills,
      reduce the associated greenhouse gases, and generate compost or biogas. While
      OCPs tend to focus on infrastructure, they often overlook the linchpin role that
      household behavior change plays in the success of OCPs. The current research used
      a longitudinal field experiment (n=370) to test both the effectiveness of a new
      curbside OCP and new social innovations intended to stimulate pro-environmental
      changes in household behavior. The findings suggest greater participation levels
      occur by implementing both new supportive infrastructure (i.e., curbside carts
      and collection services), and innovations that target the social aspects of waste
      (i.e., communicating social norms of separation). The data also provide an
      opportunity to test new model for predicting the most efficacious behavior-change
      interventions based on population profiles. The results provide some support for
      the model; reducing barriers (i.e., curbside carts and collection) tends to help
      all population profiles, but norm communication increases participation more for
      the hypothesized profile than for other sub-groups.

PMID- 28757219
TI  - Olivine, dolomite and ceramic filters in one vessel to produce clean gas from
      biomass.
AB  - Heavy organic compounds produced during almond shells gasification in a steam
      and/or air atmosphere, usually called tar, are drastically reduced in the product
      gas by using simultaneously in one vessel a ceramic filter placed in the
      freeboard and a mixture of olivine and dolomite particles in the fluidized bed of
      the gasifier. The content of tar in the product gas during a reference
      gasification test with air, in presence of fresh olivine particles only, was
      8600mg/Nm3 of dry gas. By gasifying biomass with steam at the same temperature
      level of 820 degrees C in a bed of olivine and dolomite (20% by weight), and in
      the presence of a catalytic ceramic filter inserted in the freeboard of the
      fluidized bed gasifier, the level of tar was brought down to 57mg/Nm3 of dry
      producct gas, with a decrease of more than two orders of magnitude.

PMID- 28757220
TI  - An environmental friendly animal waste disposal process with ammonia recovery and
      energy production: Experimental study and economic analysis.
AB  - Animal manure waste is considered as an environmental challenge especially in
      farming areas mainly because of gaseous emission and water pollution. Among all
      the pollutants emitted from manure waste, ammonia is of greatest concern as it
      could contribute to formation of aerosols in the air and could hardly be
      controlled by traditional disposal methods like landfill or composting. On the
      other hand, manure waste is also a renewable source for energy production. In
      this work, an environmental friendly animal waste disposal process with combined
      ammonia recovery and energy production was proposed and investigated both
      experimentally and economically. Lab-scale feasibility study results showed that
      70% of ammonia in the manure waste could be converted to struvite as fertilizer,
      while solid manure waste was successfully gasified in a 10kW downdraft fixed-bed
      gasifier producing syngas with the higher heating value of 4.9MJ/(Nm3). Based on
      experimental results, economic study for the system was carried out using a cost
      benefit analysis to investigate the financial feasibility based on a Singapore
      case study. In addition, for comparison, schemes of gasification without ammonia
      removal and incineration were also studied for manure waste disposal. The results
      showed that the proposed gasification-based manure waste treatment process
      integrated with ammonia recovery was most financially viable.

PMID- 28757221
TI  - An empirical model for prediction of household solid waste generation rate - A
      case study of Dhanbad, India.
AB  - Accurate prediction of the quantity of household solid waste generation is very
      much essential for effective management of municipal solid waste (MSW). In actual
      practice, modelling methods are often found useful for precise prediction of MSW
      generation rate. In this study, two models have been proposed that established
      the relationships between the household solid waste generation rate and the
      socioeconomic parameters, such as household size, total family income, education,
      occupation and fuel used in the kitchen. Multiple linear regression technique was
      applied to develop the two models, one for the prediction of biodegradable MSW
      generation rate and the other for non-biodegradable MSW generation rate for
      individual households of the city Dhanbad, India. The results of the two models
      showed that the coefficient of determinations (R2) were 0.782 for biodegradable
      waste generation rate and 0.676 for non-biodegradable waste generation rate using
      the selected independent variables. The accuracy tests of the developed models
      showed convincing results, as the predicted values were very close to the
      observed values. Validation of the developed models with a new set of data
      indicated a good fit for actual prediction purpose with predicted R2 values of
      0.76 and 0.64 for biodegradable and non-biodegradable MSW generation rate
      respectively.

PMID- 28757222
TI  - Internet of things and Big Data as potential solutions to the problems in waste
      electrical and electronic equipment management: An exploratory study.
AB  - Management of Waste Electrical and Electronic Equipment (WEEE) is a vital part in
      solid waste management, there are still some difficult issues require
      attentionss. This paper investigates the potential of applying Internet of Things
      (IoT) and Big Data as the solutions to the WEEE management problems. The massive
      data generated during the production, consumption and disposal of Electrical and
      Electronic Equipment (EEE) fits the characteristics of Big Data. Through using
      the state-of-the-art communication technologies, the IoT derives the WEEE "Big
      Data" from the life cycle of EEE, and the Big Data technologies process the WEEE
      "Big Data" for supporting decision making in WEEE management. The framework of
      implementing the IoT and the Big Data technologies is proposed, with its multiple
      layers are illustrated. Case studies with the potential application scenarios of
      the framework are presented and discussed. As an unprecedented exploration, the
      combined application of the IoT and the Big Data technologies in WEEE management
      brings a series of opportunities as well as new challenges. This study provides
      insights and visions for stakeholders in solving the WEEE management problems
      under the context of IoT and Big Data.

PMID- 28757223
TI  - Benefits to decomposition rates when using digestate as compost co-feedstock:
      Part II - Focus on microbial community dynamics.
AB  - Linkage between composting reactor performance and microbial community dynamics
      was investigated during co-composting of digestate and fresh feedstock (organic
      fraction of municipal solid waste) using 25L reactors. Previously, the
      relationship between composting performance and various physicochemical
      parameters were reported in Part I of the study (Arab and McCartney, 2017). Three
      digestate to fresh feedstock ratios (0, 40, and 100%; wet weight basis) were
      selected for analysis of microbial community dynamics. The 40% ratio was selected
      because it was found to perform the best (Arab and McCartney, 2017). Illumina
      sequencing results revealed that the reactor with a greater composting
      performance (higher organic matter degradation and higher heat generation; 40%
      ratio) was associated with higher microbial diversity. Two specific bacterial
      orders that might result in higher performance were Thermoactinomycetaceae and
      Actinomycetales with a higher sequence abundance during thermophilic composting
      phase and during the maturing composting phase, respectively. Galactomyces,
      Pichia, Chaetomium, and Acremonium were the four fungal genera that are probably
      also involved in higher organic matter degradation in the reactor with better
      performance. The redundancy analysis (RDA) biplot indicated that among the
      studied environmental variables, temperature, total ammonia nitrogen and nitrate
      concentration accounted for much of the major shifts in microbial sequence
      abundance during the co-composting process.

PMID- 28757224
TI  - Comparison of different MSWI fly ash treatment processes on the thermal behavior
      of As, Cr, Pb and Zn in the ash.
AB  - To reduce heavy metal leaching and stabilize municipal solid waste incineration
      (MSWI) fly ash, different methods and combination of methods were tested: water
      washing, electrodialytic separation and thermal treatment at 1000 degrees C. A
      comparison of heavy metal concentration and leaching levels of As, Cr, Pb and Zn
      for the different untreated and treated ashes was made. The results showed that
      minimizing leaching to meet the limiting values of the all the studied heavy
      metals can be obtained at the same time by combining water washing,
      electrodialytic separation and thermal treatment. The ash subjected to this
      combination had lower Cr than the ash solely subjected to thermal treatment or
      subjected to water washing prior to thermal treatment. The electrodialytic
      separation (EDS) of the washed ash lowered pH from alkaline to acidic, which
      resulted in elevated leaching of Cd and Zn, while the Cr leaching was reduced. Up
      to 58.6% of Zn and 5.5% of Pb were extracted by EDS compared to less than 0.6%
      extraction by water washing. During thermal treatment of the EDS treated ash, the
      ash was re-alkalized. Due to solidification and possibly evaporation, most heavy
      elements left in the thermally treated ash were stabilized and immobilized.
      However, leaching of As and/or Cr was still problematic and did not meet the
      limit value for the thermally treated ash being recycled in construction work.
      The removal of Ca and decomposition of Ca oxides and minerals during EDS was
      linked to the leaching patterns of As and Cr after thermal treatment.

PMID- 28757227
TI  - Post-Intensive Care Syndrome: The Role of Geriatric Psychiatry in Research,
      Practice, and Policy.

PMID- 28757226
TI  - Preparation and physicochemical characterization of ingredients of Indian
      traditional medicine, Mahamrutyunjaya Rasa.
AB  - BACKGROUND: Mahamrutyunjaya rasa is an ayurvedic formulation used in the
      treatment of cardiac disorders. It contains the purified roots of Visa (Aconitum
      ferox), Brihati (Solanum indicum), fruits of Pippali Kana (Piper longum), Marica
      (Piper nigrum), Gandhaka (Sulfur), Hingula (Cinnabar) and Tankana (Sodium
      metaborate) as per Bhaishajya Ratnavali. The purification (shodhana) process
      changes the physiochemical properties of the raw materials which need to be
      studied and understood. OBJECTIVE: The present work aims to perform a
      comprehensive physicochemical characterization of raw materials, intermediates
      and the final product obtained during purification, using modern analytical
      techniques. MATERIALS AND METHODS: The standard methods as per traditional text
      were followed and the physicochemical changes were also investigated by
      collecting samples at different steps of purification. The samples were analysed
      using various techniques, viz. Fourier transform infra-red spectroscopic (FTIR),
      X-ray diffraction (XRD), Differential Scanning Calorimeter (DSC) and High
      Performance thin Layer chromatography (HPTLC). RESULTS: The FTIR and HPTLC
      analysis of the alkaloidal extracts of Visa showed loss of an ester group with
      shift in the peaks from 1720 cm-1 (CO stretching of esters) to 1676 cm-1 (CO
      stretching of Ketone) which signifies the conversion of alkaloid Aconitine (LD50 
      0.08 mg/kg) to Benzoylaconine (LD50 - 24 mg/kg) improving its safety. The
      analysis of gandhaka by XRD and DSC showed that purification brought about
      transformation of orthorhombic sulphur into monoclinic sulphur and it reverted
      back to original form with higher purity. The treatments given to gandhaka and
      hingula with organic compounds made them homologous to the body tissues. Analysis
      of purified tankana showed that the processing led to loss of water and slight
      change in the crystal structure with the shift in the endothermic peak from 110.6
      degrees C to 104.2  degrees C. CONCLUSION: Thus, the present study provides a
      scientific backing to the methodologies used by Ayurvedic practitioners. The
      study also provides physicochemical fingerprints for the standardization as well
      as characterization of raw materials and forms a technical platform for
      manufacturers to develop quality control standards.

PMID- 28757225
TI  - Clinical evaluation of Vatari guggulu, Maharasnadi kwatha and Narayan taila in
      the management of osteoarthritis knee.
AB  - BACKGROUND: In present era, pharmacological, bio-chemical and surgical
      interventions are not success remedy for Osteoarthritis (OA). Ayurveda and other
      complementary medicine have medication for OA. OBJECTIVES: The main aim of the
      study was to assess the efficacy and safety of therapeutic combination of Vatari
      guggulu along with Maharasnadi kwatha and Narayan taila with gentle massage for
      15 min daily up to 12 weeks on affected knee joint pain assessed on Visual
      analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis
      Index (WOMAC). MATERIALS AND METHODS: It was an open label, multicentre,
      prospective, clinical study conducted on 142 patients of OA Knee. Vatari guggulu
      500 mg thrice in a day along with Maharasnadi kwatha 20 ml with equal amount of
      water twice daily and Narayan taila 20 ml twice in a day for external application
      with gentle massage for 15 min up to 12 weeks were used to all the study
      participants. RESULTS: VAS, WOMAC score and clinical symptoms were reduced
      significantly from baseline to end of the treatment (P < 0.001). CONCLUSIONS: The
      study provides good evidence in support of the efficacy and safety of the Vatari
      guggulu along with Maharasnadi kwatha and Narayan taila in the management of
      Osteoarthritis knee.

PMID- 28757228
TI  - Cluster Analysis of Acute Care Use Yields Insights for Tailored Pediatric Asthma
      Interventions.
AB  - STUDY OBJECTIVE: We undertake this study to understand patterns of pediatric
      asthma-related acute care use to inform interventions aimed at reducing
      potentially avoidable hospitalizations. METHODS: Hospital claims data from 3
      Camden city facilities for 2010 to 2014 were used to perform cluster analysis
      classifying patients aged 0 to 17 years according to their asthma-related
      hospital use. Clusters were based on 2 variables: asthma-related ED visits and
      hospitalizations. Demographics and a number of sociobehavioral and use
      characteristics were compared across clusters. RESULTS: Children who met the
      criteria (3,170) were included in the analysis. An examination of a scree plot
      showing the decline in within-cluster heterogeneity as the number of clusters
      increased confirmed that clusters of pediatric asthma patients according to
      hospital use exist in the data. Five clusters of patients with distinct asthma
      related acute care use patterns were observed. Cluster 1 (62% of patients) showed
      the lowest rates of acute care use. These patients were least likely to have a
      mental health-related diagnosis, were less likely to have visited multiple
      facilities, and had no hospitalizations for asthma. Cluster 2 (19% of patients)
      had a low number of asthma ED visits and onetime hospitalization. Cluster 3 (11%
      of patients) had a high number of ED visits and low hospitalization rates, and
      the highest rates of multiple facility use. Cluster 4 (7% of patients) had
      moderate ED use for both asthma and other illnesses, and high rates of asthma
      hospitalizations; nearly one quarter received care at all facilities, and 1 in 10
      had a mental health diagnosis. Cluster 5 (1% of patients) had extreme rates of
      acute care use. CONCLUSION: Differences observed between groups across multiple
      sociobehavioral factors suggest these clusters may represent children who differ
      along multiple dimensions, in addition to patterns of service use, with
      implications for tailored interventions.

PMID- 28757231
TI  - Erratum.

PMID- 28757229
TI  - Prenatal particulate matter exposure and wheeze in Mexican children: Effect
      modification by prenatal psychosocial stress.
AB  - BACKGROUND: Air pollution exposure in childhood is associated with greater
      incidence and exacerbation of asthma, particularly in children whose parents
      report high levels of psychological stress. However, this interaction has not
      been completely elucidated in pregnancy. OBJECTIVE: To examine whether the
      association between prenatal exposure to particulate matter no larger than 2.5
      MUm in diameter (PM2.5) and wheeze in children is modified by prenatal stress.
      METHODS: Mexican women were recruited during pregnancy (N = 552). Residential
      prenatal daily exposure to PM2.5 was estimated using a satellite-based
      spatiotemporally resolved prediction model and averaged over trimesters. Maternal
      stress was indexed by maternal negative life events (NLE) score (range 0-11)
      ascertained during mid to late pregnancy. NLE scores were dichotomized at the
      median as low (NLE score <= 3) and high (NLE score > 3) stress. Reports of ever
      wheeze and wheeze in the past 12 months (current wheeze) for children were
      obtained using the International Study of Asthma and Allergies in Childhood
      survey at 48 months. The association between prenatal PM2.5 and wheeze was
      analyzed using a modified Poisson regression and stratified by low vs high
      stress. RESULTS: Greater PM2.5 exposure during the first trimester was associated
      with increased risk of current wheeze among children with mothers reporting high
      prenatal stress (relative risk 1.35, 95% confidence interval 1.00-1.83, per
      interquartile range increase 3.8 MUg/m3) but not among those reporting low stress
      (relative risk 0.84, 95% confidence interval 0.61-1.16, per interquartile range
      increase 3.8 MUg/m3; P for interaction = .04). CONCLUSION: Increased prenatal
      stress enhanced the association between PM2.5 exposure in early pregnancy, and
      child wheeze at 48 months of age. It is important to consider chemical and
      nonchemical stressors together to more comprehensively characterize children's
      environmental risk.

PMID- 28757230
TI  - Vitamin D, high-sensitivity C-reactive protein, and airway hyperresponsiveness in
      infants with recurrent respiratory symptoms.
AB  - BACKGROUND: Vitamin D insufficiency might be associated with biased T-cell
      responses resulting in inflammatory conditions such as atopy and asthma. Little
      is known about the role of vitamin D in low-grade systemic inflammation and
      airway hyperresponsiveness (AHR) in young children. OBJECTIVE: To evaluate
      whether vitamin D insufficiency and increased serum high-sensitivity C-reactive
      protein (hs-CRP) are linked to AHR in symptomatic infants. METHODS: Seventy-nine
      infants with recurrent or persistent lower respiratory tract symptoms underwent
      comprehensive lung function testing and a bronchial methacholine challenge test.
      In addition, skin prick tests were performed and serum 25-hydroxyvitamin D (S-25
      OHD), hs-CRP, total immunoglobulin E, and blood eosinophil levels were
      determined. RESULTS: S-25-OHD was lowest in infants with blood eosinophilia and
      AHR (n = 10) compared with those with eosinophilia only (n = 6) or AHR only (n =
      50) or those with neither (n = 13; P = .035). Moreover, vitamin D insufficiency
      (S-25-OHD <50 nmol/L) was most common in infants with blood eosinophilia and AHR
      (P = .041). Serum hs-CRP was lower in infants with recurrent physician-diagnosed
      wheezing (P = .048) and in those with blood eosinophilia (P = .015) than in
      infants without these characteristics and was not associated with S-25-OHD or
      AHR. S-25-OHD levels were significantly lower (median 54 nmol/L) during the
      autumn-winter season than in the spring-summer season (median 63 nmol/L; P =
      .026). CONCLUSION: Vitamin D insufficiency could underlie eosinophilia and AHR in
      infants with troublesome lung symptoms, whereas hs-CRP-mediated low-grade
      systemic inflammation is rare in early childhood wheezing.

PMID- 28757232
TI  - The joy of heartfelt music: An examination of emotional and physiological
      responses.
AB  - Music-listening can be a powerful therapeutic tool for mood rehabilitation, yet
      quality evidence for its validity as a singular treatment is scarce.
      Specifically, the relationship between music-induced mood improvement and
      meaningful physiological change, as well as the influence of music- and person
      related covariates on these outcomes are yet to be comprehensively explored.
      Ninety-four healthy participants completed questionnaires probing demographics,
      personal information, and musical background. Participants listened to two
      prescribed musical pieces (one classical, one jazz), an "uplifting" piece of
      their own choice, and an acoustic control stimulus (white noise) in randomised
      order. Physiological responses (heart rate, respiration, galvanic skin response)
      were recorded throughout. After each piece, participants rated their subjective
      responses on a series of Likert scales. Subjectively, the self-selected pieces
      induced the most joy, and the classical piece was perceived as most relaxing,
      consistent with the arousal ratings proposed by a music selection panel. These
      two stimuli led to the greatest overall improvement in composite emotional state
      from baseline. Psycho-physiologically, self-selected pieces often elicited a
      "eustress" response ("positive arousal"), whereas classical music was associated
      with the highest heart rate variability. Very few person-related covariates
      appeared to affect responses, and music-related covariates (besides self
      selection) appeared arbitrary. These data provide strong evidence that optimal
      music for therapy varies between individuals. Our findings additionally suggest
      that the self-selected music was most effective for inducing a joyous state;
      while low arousal classical music was most likely to shift the participant into a
      state of relaxation. Therapy should attempt to find the most effective and
      "heartfelt" music for each listener, according to therapeutic goals.

PMID- 28757233
TI  - Cognitive conflict increases processing of negative, task-irrelevant stimuli.
AB  - The detection of cognitive conflict is thought to trigger adjustments in
      executive control. It has been recently shown that cognitive conflict increases
      processing of stimuli that are relevant to the ongoing task and that these
      modulations are exerted by the dorsolateral prefrontal cortex (DLPFC). However,
      it is still unclear whether such control influences are unspecific and might also
      affect the processing of task-irrelevant stimuli. The aim of the study was to
      examine if cognitive conflict affects processing of neutral and negative, task
      irrelevant pictures. Participants responded to congruent (non-conflict) or to
      incongruent (conflict-eliciting) trials of a modified flanker task. Each response
      was followed by a presentation of a neutral or negative picture. The late
      positive potential (LPP) in response to picture presentation was used to assess
      the level of picture processing after conflict vs non-conflict trials.
      Connectivity between the DLPFC and attentional and perceptual areas during
      picture presentation was analysed to check if the DLPFC might be a source of
      these modulations. ERP results showed an effect of cognitive conflict only on
      processing of negative pictures: LPP in response to negative pictures was
      increased after conflict trials, whereas LPP in response to neutral pictures
      remained unchanged. Cortical connectivity analysis showed that conflict trials
      intensified information flow from the DLPFC towards attentional and perceptual
      regions. Results suggest that cognitive conflict increases processing of task
      irrelevant stimuli; however, they must display high biological salience. Increase
      in cognitive control exerted by the DLPFC over attentional and perceptual regions
      is a probable mechanism of the effect.

PMID- 28757234
TI  - Non-contact measurement of heart response reflected in human eye.
AB  - This study aims to develop a non-contact measurement technique for cardiac
      response that uses an infrared image of the patient's pupil. The pupil
      contraction rhythm is related to the autonomic balance and major organs (such as
      the heart) via a neural pathway. In this study, the response of the heart was
      determined by analyzing the pupillary rhythm based on the harmonic frequencies
      between them. Seventy undergraduate volunteers of both genders, (35 females and
      35 males), with ages ranging between 20 and 30years (mean: 24.52+/-0.64years)
      were asked to conduct a simple conversation, perform slight movements, and
      experience sound stimuli to evoke arousal, relaxation, happiness, sadness, or a
      neutral mood in this experiment. Electrocardiograms and pupil images were
      measured and analyzed, and the harmonic frequencies were identified to determine
      the relational response. The cardiac time (heart rate (HR), beats per minute
      (BPM), the standard deviation of the normal-to-normal (NN) intervals (SDNN), the
      mean squared differences in the successive N-N intervals (rMSSD), and the
      percentage difference between adjacent normal interbeat (R-R) intervals>50
      (pNN50)) and frequency (very low frequency (VLF), low frequency (LF), high
      frequency (HF), VLF/HF, and LF/HF) parameters were also observed with regard to
      the effects of the movement, conversation, and physiological state. The cardiac
      response was stable, showing less significance than the effects of the three
      conditions. Therefore, multi-cardiac measurements were successfully obtained from
      a simple, low-cost, non-invasive, and non-contact data acquisition method in this
      study.

PMID- 28757235
TI  - Adult onset Still's disease-The evidence that anti-interleukin-1 treatment is
      effective and well-tolerated (a comprehensive literature review).
AB  - The literature contains many reports of the use of commercially available anti-IL
      1 agents (anakinra/Kineret(r), canakinumab/Ilaris(r), or rilonacept/Arcalyst(r))
      in treatment-resistant adult-onset Still's disease (AOSD). These have been widely
      summarized in many review articles, but a full account of all reports with each
      of the agents used is not available. This literature review includes all reports
      of treatment outcomes in patients treated for AOSD with any commercially
      available anti-IL-1 agent (excluding cases of unconfirmed or atypical AOSD or
      treatments only for rare AOSD complications). The summary makes use of tabular
      formats, to identify the available reports and to provide data for compiling and
      comparison to classical therapies. For each anti-IL-1 agent used, a table shows
      the frequency of remission during treatment and the frequency of stopping or
      reducing steroid use, which were reported in almost all articles. A brief textual
      summary is used to describe other relevant but less often described efficacy
      aspects and any safety information. The compiled data show that treatment with
      all anti-IL-1 agents is effective in AOSD, indicating that IL-1 has a central
      role in the pathogenesis of AOSD. Rates of full or partial remission with each
      agent were similar to each other (91-100%) and superior to the outcomes published
      for classical therapies. Primary treatment failures were rare, but efficacy was
      lost over time in some cases. Of note, the newer anti-IL-1 agents with longer
      half-lives may show prolonged efficacy. An articular involvement seems to be less
      responsive than systemic features of disease. However, long-term follow-up shows
      that efficacy may persist for many years. There is substantial evidence that anti
      IL-1 agents have a strong steroid-sparing effect and considerable evidence that
      the use of disease-modifying anti-rheumatic drugs can also be reduced or stopped.
      Thus, the use of anti-IL-1 agents may reduce the side-effects of co-treatment.
      The high response rate to anti-IL-1 agents, especially in refractory AOSD cases,
      suggests that their appropriate use in a timely manner can slow disease
      progression and reduce treatment side-effects.

PMID- 28757236
TI  - Fiber-based modeling of in situ ankle ligaments with consideration of progressive
      failure.
AB  - Ligament sprains account for a majority of injuries to the foot and ankle complex
      among athletic populations. The infeasibility of measuring the in situ response
      and load paths of individual ligaments has precluded a complete characterization
      of their mechanical behavior via experiment. In the present study a fiber-based
      modeling approach of in situ ankle ligaments was developed and validated for
      determining the heterogeneous force-elongation characteristics and the consequent
      injury patterns. Nine major ankle ligaments were modeled as bundles of discrete
      elements, corresponding functionally to the structure of collagen fibers. To
      incorporate the progressive nature of ligamentous injury, the limit strain at the
      occurrence of fiber failure was described by a distribution function ranging from
      12% to 18% along the width of the insertion site. The model was validated by
      comparing the structural kinetic and kinematic response obtained experimentally
      and computationally under well-controlled foot rotations. The simulation results
      replicated the 6 degree-of-freedom bony motion and ligamentous injuries and, by
      implication, the in situ deformations of the ligaments. Gross stiffness of the
      whole ligament derived from the fibers was comparable to existing experimental
      data. The present modeling approach provides a biomechanically realistic,
      interpretable and computationally efficient way to characterize the in situ
      ligament slack, sequential and heterogeneous uncrimping of collagen fascicles and
      failure propagation as the external load is applied. Applications of this model
      include functional ankle joint mechanics, injury prevention and countermeasure
      design for athletes.

PMID- 28757237
TI  - Ultrasound induced strain cytoskeleton rearrangement: An experimental and
      simulation study.
AB  - Cytoskeleton and specially actin filaments are responsible for mechanical
      modulation of cellular behavior. These structures could be fluidized in response
      to transient mechanical cues. Ultrasound devices have been widely used in
      medicine which their generated ultrasonic waves could disrupt/fluidize actin
      filaments in cytoskeleton and thus could affect cellular organization. Present
      research aims at revealing the mechanism of fluidization caused by ultrasound
      induced strains. First, a numerical simulation was performed to reveal the effect
      of oscillating ultrasonic pressure on induced deformation in the cell with
      respect to different cell geometries and exposure conditions. The model revealed
      that higher pressure and frequencies induce higher levels of strain in the cell.
      The results also showed that spread cells are more exposed to cytomechanical
      remodeling due to higher level of ultrasound induced deformations but also the
      effect of harmonic excitation decreases with spreading. Furthermore, strain
      values found to be less in the nucleus comparing the value in the cytoplasm, but
      still these strains can affect the behavior of the cell through
      mechanotransduction mechanisms. Then, different experimental ultrasound protocols
      were used to evaluate their effects on cell viability and actin cytoskeleton
      distribution. Results of Live/Dead assay indicated that high pressure and
      duration of the exposure had negative effects on the viability of C2C12 cells,
      while the viability ratio still remained above 85%. In addition, actin
      fluorescent staining showed that high levels of filament disruption could occur
      with increasing the pressure. The results of this study shed light on cellular
      response to mechanical stimuli applied by ultrasonic waves.

PMID- 28757238
TI  - The effect of uphill and downhill walking on gait parameters: A self-paced
      treadmill study.
AB  - It has been shown that gait parameters vary systematically with the slope of the
      surface when walking uphill (UH) or downhill (DH) (Andriacchi et al., 1977; Crowe
      et al., 1996; Kawamura et al., 1991; Kirtley et al., 1985; McIntosh et al., 2006;
      Sun et al., 1996). However, gait trials performed on inclined surfaces have been
      subject to certain technical limitations including using fixed speed treadmills
      (TMs) or, alternatively, sampling only a few gait cycles on inclined ramps.
      Further, prior work has not analyzed upper body kinematics. This study aims to
      investigate effects of slope on gait parameters using a self-paced TM (SPTM)
      which facilitates more natural walking, including measuring upper body kinematics
      and gait coordination parameters. Gait of 11 young healthy participants was
      sampled during walking in steady state speed. Measurements were made at slopes of
      +10 degrees , 0 degrees  and -10 degrees . Force plates and a motion capture
      system were used to reconstruct twenty spatiotemporal gait parameters. For
      validation, previously described parameters were compared with the literature,
      and novel parameters measuring upper body kinematics and bilateral gait
      coordination were also analyzed. Results showed that most lower and upper body
      gait parameters were affected by walking slope angle. Specifically, UH walking
      had a higher impact on gait kinematics than DH walking. However, gait
      coordination parameters were not affected by walking slope, suggesting that gait
      asymmetry, left-right coordination and gait variability are robust
      characteristics of walking. The findings of the study are discussed in reference
      to a potential combined effect of slope and gait speed. Follow-up studies are
      needed to explore the relative effects of each of these factors.

PMID- 28757240
TI  - Reply by the Authors.

PMID- 28757241
TI  - Robotic Salvage Pyeloplasty With Buccal Mucosal Onlay Graft: Video Demonstration
      of Technique and Outcomes.
AB  - OBJECTIVE: To present the use of buccal mucosal graft (BMG) in a salvage robotic
      laparoscopic pyeloplasty as an alternative in the management of a recurrent
      ureteropelvic junction (UPJ) obstruction. METHODS: We present 2 patients with a
      recurrent UPJ obstruction who had previously undergone 2 prior open or robotic
      pyleoplasties, followed by endoscopic management. Preoperative imaging was
      obtained before surgical repair. The UPJ was incised and the incision extended to
      reveal margins of a healthy normal-caliber ureteral tissue. Single BMGs were
      harvested from the inner cheek of each patient. The grafts were of sufficient
      caliber and size to cover the entire defect as an onlay graft, and to maintain a
      tension-free and watertight anastomosis. RESULTS: The operative time was between
      188 and 284 minutes. The estimated blood loss was 25-50 mL. The hospital stay was
      2 days for each patient. Foley catheters were removed before discharge and the
      Jackson-Pratt drains were removed in the immediate postoperative period. The
      ureteral stents were removed at 6 and 9 weeks, with retrograde pyelograms
      confirming patency at the UPJ. Lasix renograms were obtained after 4 months and
      either demonstrated a resolution or were equivocal for obstruction, with a
      preservation of renal function. Both patients have been without complication
      since the stent removal. CONCLUSION: Robotic pyeloplasty with BMG is an
      alternative in the management of recurrent UPJ obstructions. Short-term follow-up
      has demonstrated that it is an effective and attractive approach compared with
      more extensive and invasive surgeries such as a renal autotransplant and an ileal
      ureter.

PMID- 28757239
TI  - Beyond mRNA: The role of non-coding RNAs in normal and aberrant hematopoiesis.
AB  - The role of non-coding Ribonucleic Acids (ncRNAs) in biology is currently an area
      of intense focus. Hematopoiesis requires rapidly changing regulatory molecules to
      guide appropriate differentiation and ncRNA are well suited for this. It is not
      surprising that virtually all aspects of hematopoiesis have roles for ncRNAs
      assigned to them and doubtlessly much more await characterization. Stem cell
      maintenance, lymphoid, myeloid and erythroid differentiation are all regulated by
      various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and
      various transposable elements within the genome. As our understanding of the many
      and complex ncRNA roles continues to grow, new discoveries are challenging the
      existing classification schemes. In this review we briefly overview the broad
      categories of ncRNAs and discuss a few examples regulating normal and aberrant
      hematopoiesis.

PMID- 28757242
TI  - Mental workload and motor performance dynamics during practice of reaching
      movements under various levels of task difficulty.
AB  - The assessment of mental workload can inform attentional resource allocation
      during task performance that is essential for understanding the underlying
      principles of human cognitive-motor behavior. While many studies have focused on
      mental workload in relation to human performance, a modest body of work has
      examined it in a motor practice/learning context without considering individual
      variability. Thus, this work aimed to examine mental workload by employing the
      NASA TLX as well as the changes in motor performance resulting from the practice
      of a novel reaching task. Two groups of participants practiced a reaching task at
      a high and low nominal difficulty during which a group-level analysis assessed
      the mental workload, motor performance and motor improvement dynamics. A
      secondary cluster analysis was also conducted to identify specific individual
      patterns of cognitive-motor responses. Overall, both group- and cluster-level
      analyses revealed that: (i) all participants improved their performance
      throughout motor practice, and (ii) an increase in mental workload was associated
      with a reduction of the quality of motor performance along with a slower rate of
      motor improvement. The results are discussed in the context of the optimal
      challenge point framework and in particular it is proposed that under the
      experimental conditions employed here, functional task difficulty: (i) would
      possibly depend on an individuals' information processing capabilities, and (ii)
      could be indexed by the level of mental workload which, when excessively
      heightened can decrease the quality of performance and more generally result in
      delayed motor improvements.

PMID- 28757243
TI  - The overlapping brain region accounting for the relationship between
      procrastination and impulsivity: A voxel-based morphometry study.
AB  - Procrastination is a prevalent problematic behavior that brings serious
      consequences, such as lower levels of health, wealth, and well-being. Previous
      research has verified that impulsivity is one of the traits most strongly
      correlated with procrastination. However, little is known about why there is a
      tight behavioral relationship between them. To address this question, we used
      voxel-based morphometry (VBM) to explore the common neural substrates between
      procrastination and impulsivity. In line with previous findings, the behavioral
      results showed a strong behavioral correlation between procrastination and
      impulsivity. Neuroimaging results showed impulsivity and procrastination shared
      the common neurobiological underpinnings in the dorsolateral prefrontal cortex
      (DLPFC) based on the data from 85 participants (sample 1). Furthermore, the
      mediation analysis revealed that impulsivity mediated the impact of gray matter
      (GM) volumes of this overlapping region in the DLPFC on procrastination on
      another independent 84 participants' data (sample 2). In conclusion, the
      overlapping brain region in the DLPFC would be responsible for the close
      relationship between procrastination and impulsivity. As a whole, the present
      study extends our knowledge on procrastination, and provides a novel perspective
      to explain the tight impulsivity - procrastination relationship.

PMID- 28757244
TI  - Inverse modulation of motor neuron cellular and synaptic properties can maintain
      the same motor output.
AB  - Although often examined in isolation, a single neuromodulator typically has
      multiple cellular and synaptic effects. Here, we have examined the interaction of
      the cellular and synaptic effects of 5-HT in the lamprey spinal cord. 5-HT
      reduces the amplitude of glutamatergic synaptic inputs and the slow post-spike
      afterhyperpolarization (sAHP) in motor neurons. We examined the interaction
      between these effects using ventral root activity evoked by stimulation of the
      spinal cord. While 5-HT reduced excitatory glutamatergic synaptic inputs in motor
      neurons to approximately 60% of control, ventral root activity was not
      significantly affected. The reduction of the sAHP by 5-HT increased motor neuron
      excitability by reducing spike frequency adaptation, an effect that could in
      principle have opposed the reduction of the excitatory synaptic input. Support
      for this was sought by reducing the amplitude of the sAHP by applying the toxin
      apamin before 5-HT application. In these experiments, 5-HT reduced the ventral
      root response, presumably because the reduction of the synaptic input now
      dominated. This was supported by computer simulations that showed that the motor
      output could be maintained over a wide range of synaptic input values if they
      were matched by changes in postsynaptic excitability. The effects of 5-HT on
      ventral root responses were altered by spinal cord lesions: 5-HT significantly
      increased ventral root responses in animals that recovered good locomotor
      function, consistent with a lesion-induced reduction in the synaptic effects of 5
      HT, which thus biases its effects to the increase in motor neuron excitability.

PMID- 28757245
TI  - Long-term voluntary exercise prevents post-weaning social isolation-induced
      cognitive impairment in rats.
AB  - This study aimed to determine the effect of exercise on locomotion, anxiety
      related behavior, learning, and memory in socially isolated post-weaning rats, as
      well as the correlation between exercise and the concentration of brain-derived
      neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus. Rats
      were randomly assigned to three groups: the control group; the social isolation
      group; the social isolation plus exercise (SIE) group. Social isolation
      conditions, with or without exercise were maintained for 90d, and then multiple
      behavioral tests, including the open-field test, elevated plus maze test, and
      Morris water maze (MWM) test were administered. Following behavioral assessment,
      hippocampal tissue samples were obtained for measurement of BDNF and NGF. There
      wasn't a significant difference in locomotor activity between the groups
      (P>0.05). Anxiety scores were higher in the socially isolated group (P<0.05) than
      in the SIE group (P<0.05). According to the probe trial session of the MWM test
      results, exercise training improved platform crossings' number in the socially
      isolated rats (P<0.05). Exercise training ameliorated social isolation-induced
      reduction in hippocampal BDNF and NGF content (P<0.05). These findings suggest
      that exercise training improves cognitive functions via increasing hippocampal
      BDNF and NGF concentrations in socially isolated post-weaning rats.

PMID- 28757246
TI  - Evaluation of mesenchymal stem cell modulation of trigeminal neuronal responses
      to cold.
AB  - Tissue engineering protocols, such as regenerative endodontic procedures (REPs),
      comprise biologically based procedures designed to restore normal physiologic
      function. For REPs, the goal is reconstitution of the pulp-dentin complex by
      delivering mesenchymal stem cells (MSCs), including the stem cells of the apical
      papilla (SCAP) into a root canal system. Many patients regain cold sensitivity
      after REPs, but the mechanism is not understood. We hypothesized that SCAP
      modulate nociceptive function through a paracrine mechanism that activates cold
      sensitive ion channels in neurons. We established a co-culture system with human
      SCAP and rat trigeminal (TG) sensory neurons in order to determine the effect of
      SCAP co-culture on neuronal responses using whole-cell patch-clamp
      electrophysiology. TG neurons co-cultured with SCAP demonstrated increased TRPA1
      mediated (p<0.01) and TRPM8-mediated inward current densities (p<0.01) at 24h in
      co-culture. Cold stimulation to SCAP significantly increased ATP release
      (p<0.01), and supernatant collected after cold stimulation to SCAP was able to
      activate cultured TG neurons. Co-culture with SCAP significantly increased
      sustained ATP-evoked inward current density (p<0.05). These data suggest that
      SCAP release trophic factors that act on afferent neurons to enhance cold
      sensitive ion channel activity.

PMID- 28757247
TI  - L-DOPA inhibits excitatory synaptic transmission in the rat nucleus tractus
      solitarius through release of dopamine.
AB  - The mode of action of L-DOPA on excitatory synaptic transmission in second-order
      neurons of the nucleus tractus solitarius (NTS) was studied using the rat
      brainstem slices. Superfusion of L-DOPA (10MUM) reduced the frequency of
      miniature excitatory postsynaptic currents (mEPSCs) without any effect on the
      amplitude. A low concentration (1MUM) was ineffective on the mEPSCs, and the
      highest concentration (100MUM) exerted a stronger inhibitory effect. L-DOPA
      (10MUM) decreased the amplitude of EPSCs (eEPSCs) evoked by electrical
      stimulation of the tractus solitarius and increased the paired-pulse ratio. The
      inhibitory effects of L-DOPA on mEPSCs and eEPSCs were similar to those of
      dopamine (100MUM). The effects of L-DOPA were blocked by a competitive
      antagonist, L-DOPA methyl ester (100MUM) and also by a D2 receptor antagonist,
      sulpiride (10MUM), while those of dopamine were blocked by the latter but not by
      the former. In reserpine (5mg/kg, s.c.)-treated rats, the effects of L-DOPA on
      both mEPSCs and eEPSCs were completely abolished, but those of dopamine remained
      unchanged. The present results suggest a possibility that L-DOPA may induce the
      release of dopamine from the axon terminals in the NTS and the released dopamine
      suppresses the glutamatergic transmission through activation of the presynaptic
      D2 receptors.

PMID- 28757248
TI  - Response characteristics of the cat somatosensory cortex following the mechanical
      stimulation to non-vital and vital canine.
AB  - Patients sometimes complain that non-vital teeth after root canal treatment (RCT)
      are paresthesia compared with vital teeth, and previous psychological studies on
      the tactile sensibility of non-vital teeth remained controversial. In the present
      study, intrinsic signal optical imaging, which served as an objective tool, was
      employed to compare the cortex response characteristics following forces applied
      to the cat non-vital and vital canines. Based on the evoked cortical responses,
      the response threshold, signal strength, spatial pattern, temporal dynamics and
      the preference of force direction, they were not significantly different between
      vital and non-vital canines. It seemed that the tactile sensibility of vital and
      non-vital teeth was comparable at the cortical response level, and pulpal
      receptors were not concerned in tactile function.

PMID- 28757249
TI  - Seasonal and sex differences in cell proliferation, neurogenesis, and cell death
      within the dentate gyrus of adult wild-caught meadow voles.
AB  - Past research indicates that female meadow voles (Microtus pennsylvanicus) show
      decreased neurogenesis within the hippocampus during the breeding season relative
      to the non-breeding season, whereas male voles show no such seasonal changes. We
      expanded upon these results by quantifying a variety of endogenous cell
      proliferation and neurogenesis markers in wild-caught voles. Adult male and
      female voles were captured in the summer (breeding season) or fall (non-breeding
      season), and blood samples and brain tissue were collected. Four cellular markers
      (pHisH3, Ki67, DCX, and pyknosis) were labeled and then quantified using either
      fluorescent or light microscopy. The volume of the cell layers within the dentate
      gyrus (hilus and granule cell layer) was significantly larger in males than in
      females. In both sexes, all the cellular markers decreased significantly in the
      dentate gyrus during the breeding season relative to the non-breeding season,
      indicating decreased cell proliferation, neurogenesis, and pyknosis. Only the
      pHisH3 marker showed a sex difference, with females having a greater density of
      this cell proliferation marker than males. During the breeding season relative to
      the non-breeding season, males and females showed the predicted significant
      increases in testosterone and estradiol, respectively. Overall, these results
      suggest higher levels of neuronal turn-over during the non-breeding season
      relative to the breeding season, possibly due to seasonal changes in sex
      steroids.

PMID- 28757250
TI  - Optogenetic activation of amygdala projections to nucleus accumbens can arrest
      conditioned and unconditioned alcohol consummatory behavior.
AB  - Following a Pavlovian pairing procedure, alcohol-paired cues come to elicit
      behavioral responses that lead to alcohol consumption. Here we used an
      optogenetic approach to activate basolateral amygdala (BLA) axonal terminals
      targeting the shell of nucleus accumbens (AcbSh) and investigated a possible
      influence over cue-conditioned alcohol seeking and alcohol drinking, based on the
      demonstrated roles of these areas in behavioral responding to Pavlovian cues and
      in feeding behavior. Rats were trained to anticipate alcohol or sucrose following
      the onset of a discrete conditioned stimulus (CS). Channelrhodopsin-mediated
      activation of the BLA-to-AcbSh pathway concurrent with each CS disrupted cued
      alcohol seeking. Activation of the same pathway caused rapid cessation of alcohol
      drinking from a sipper tube. Neither effect was accompanied by an overall change
      in locomotion. Finally, the suppressive effect of photoactivation on cued
      triggered seeking was also evidenced in animals trained with sucrose. Together
      these findings suggest that photoactivation of BLA terminals in the AcbSh can
      override the conditioned motivational properties of reward-predictive cues as
      well as unconditioned consummatory responses necessary for alcohol drinking. The
      findings provide evidence for a limbic-striatal influence over motivated behavior
      for orally consumed rewards, including alcohol.

PMID- 28757251
TI  - The Molecular Architecture for RNA-Guided RNA Cleavage by Cas13a.
AB  - Cas13a, a type VI-A CRISPR-Cas RNA-guided RNA ribonuclease, degrades invasive
      RNAs targeted by CRISPR RNA (crRNA) and has potential applications in RNA
      technology. To understand how Cas13a is activated to cleave RNA, we have
      determined the crystal structure of Leptotrichia buccalis (Lbu) Cas13a bound to
      crRNA and its target RNA, as well as the cryo-EM structure of the LbuCas13a-crRNA
      complex. The crRNA-target RNA duplex binds in a positively charged central
      channel of the nuclease (NUC) lobe, and Cas13a protein and crRNA undergo a
      significant conformational change upon target RNA binding. The guide-target RNA
      duplex formation triggers HEPN1 domain to move toward HEPN2 domain, activating
      the HEPN catalytic site of Cas13a protein, which subsequently cleaves both single
      stranded target and collateral RNAs in a non-specific manner. These findings
      reveal how Cas13a of type VI CRISPR-Cas systems defend against RNA phages and set
      the stage for its development as a tool for RNA manipulation.

PMID- 28757252
TI  - Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo.
AB  - Non-neutralizing antibodies (nnAbs) to HIV-1 show little measurable activity in
      prevention or therapy in animal models yet were the only correlate of protection
      in the RV144 vaccine trial. To investigate the role of nnAbs on HIV-1 infection
      in vivo, we devised a replication-competent HIV-1 reporter virus that expresses a
      heterologous HA-tag on the surface of infected cells and virions. Anti-HA
      antibodies bind to, but do not neutralize, the reporter virus in vitro. However,
      anti-HA protects against infection in humanized mice and strongly selects for
      nnAb-resistant viruses in an entirely Fc-dependent manner. Similar results were
      also obtained with tier 2 HIV-1 viruses using a human anti-gp41 nnAb, 246D. While
      nnAbs are demonstrably less effective than broadly neutralizing antibodies
      (bNAbs) against HIV-1 in vitro and in vivo, the data show that nnAbs can protect
      against and alter the course of HIV-1 infection in vivo. PAPERCLIP.

PMID- 28757254
TI  - Framing Obesity as a Health Issue: Differences in Public and Professional
      Perceptions Between Canada and the United States.

PMID- 28757255
TI  - Enhancement of nose-to-brain delivery of hydrophilic macromolecules with stearate
      or polyethylene glycol-modified arginine-rich peptide.
AB  - Recently, nose-to-brain delivery is a highly versatile route, which, in
      combination with novel drugs being developed for treating intractable CNS
      diseases, is a promising approach for the treatment of disorders. Furthermore,
      nano-sized drug carriers may improve nose-to-brain drug delivery by their
      capability to increase the transmucosal penetration of the drugs across nasal
      mucosal tissue barrier. However, there is still not enough information regarding
      mechanism of absorption pathway from nasal cavity to brain using nanocarriers. In
      this study, to investigate the nose-to-brain transport pathway using
      nanocarriers, the distribution in whole brain, nasal mucosa, and trigeminal nerve
      after intranasal administration of two kinds of nanocarriers which have
      hydrophobic or hydrophilic moiety. We used CHHRRRRHHC peptide (CH2R4H2C) as basic
      peptide carriers, and modified with stearic acid (STR) as a hydrophobic moiety
      (STR-CH2R4H2C) or polyethylene glycol (PEG)-based block copolymer (PEG-PCL) as
      hydrophilic moiety (PEG-PCL-CH2R4H2C). The nose-to-brain drug delivery can be
      improved by using STR-CH2R4H2C and PEG-PCL-CH2R4H2C as carriers. Specifically,
      hydrophobic STR-CH2R4H2C is more suitable for the transport of drugs targeting
      the forebrain, while PEG-PCL-modified CH2R4H2C is more suitable for transporting
      drugs targeting the hindbrain or whole brain tissue. In conclusion, the results
      of this study support the possibility that drug delivery pathways can be
      controlled depending on the properties of different carrier complexes.

PMID- 28757253
TI  - Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis.
AB  - Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human
      malignancies, owing in part to its propensity for metastasis. Here, we used an
      organoid culture system to investigate how transcription and the enhancer
      landscape become altered during discrete stages of disease progression in a PDA
      mouse model. This approach revealed that the metastatic transition is accompanied
      by massive and recurrent alterations in enhancer activity. We implicate the
      pioneer factor FOXA1 as a driver of enhancer activation in this system, a
      mechanism that renders PDA cells more invasive and less anchorage-dependent for
      growth in vitro, as well as more metastatic in vivo. In this context, FOXA1
      dependent enhancer reprogramming activates a transcriptional program of embryonic
      foregut endoderm. Collectively, our study implicates enhancer reprogramming,
      FOXA1 upregulation, and a retrograde developmental transition in PDA metastasis.

PMID- 28757256
TI  - Proposed algorithm for healthcare professionals based on product characteristics
      and in vitro performances in different use conditions using formoterol-based
      marketed products for inhalation.
AB  - Healthcare professionals require an easy algorithm for selecting the most
      appropriate inhalation product for each patient at the beginning of a treatment.
      As a case study, we selected five marketed formoterol products: Foradil(r) and
      Formagal(r), capsule-based dry powder inhalers (DPIs), Novolizer(r) Formoterol
      and Oxis(r), reservoir-based DPIs and Formoair(r), a pressurized metered dose
      inhaler. We generated an algorithm based on device properties (i.e. device
      handling, feedback and remaining dose/end of product indication) and in vitro
      aerodynamic performances (i) along the product use life in optimal conditions,
      (ii) at different airflows and (iii) after exposing pre-loaded doses to 40
      degrees C and 75% relative humidity for 4h. Based on these results, an algorithm
      was built where Formoair and Formagal can be proposed when there is high risk of
      humidity and for patients presenting suboptimal or optimal airflows. When no risk
      of humidity is present, Formoair, Foradil, Formagal and Novolizer Formoterol
      equipped with a trigger valve could be proposed for patients presenting
      suboptimal airflows. When no risk of humidity is present and for patients
      presenting optimal airflow, all products, including Oxis, could be proposed.
      Ultimately, the optimal inhalation product will be selected after checking the
      patient's preference and capacity for correct device handling and inhalation
      technique.

PMID- 28757257
TI  - Assessment of dually labelled PEGylated liposomes transplacental passage and
      placental penetration using a combination of two ex-vivo human models: the dually
      perfused placenta and the suspended villous explants.
AB  - Uptake and passage of nanocarriers through the placenta are critical information
      to develop new therapeutic approaches during pregnancy. In order to assess
      nanocarriers transplacental passage and penetration into the placenta, we studied
      and optimized two ex-vivo human models: the dually perfused placenta and the
      placenta explants. Doubly labelled PEGylated liposomes were used as models to
      provide data on the penetration and transplacental passage of drugs and
      liposomes. A HPLC method was set-up to quantify both carboxyfluorescein and lipid
      rhodamine. Transplacental passage was then quantified using HPLC and placental
      penetration was assessed using spinning disk microscopy. We found a similar
      transplacental passage rate for both free and encapsulated carboxyfluorescein as
      well as a homogeneous fluorescence intensity in the outer cell layer of the
      placental villous, the syncytiotrophoblast, and the mesenchyma. Besides, liposome
      rhodamine was not detected in the fetal circulation. The absence of
      transplacental passage of PEGylated liposomes is also supported by their
      detection in the sole syncytiotrophoblast. The combination of two ex-vivo models
      and the monitoring of both the drug and the carrier provided consistent and
      complementary information. Overall, we suggest combining the perfused human
      placenta and the human explants villous models to evaluate nanocarriers designed
      for treatments during pregnancy.

PMID- 28757258
TI  - BDNF over-expression induces striatal serotonin fiber sprouting and increases the
      susceptibility to l-DOPA-induced dyskinesia in 6-OHDA-lesioned rats.
AB  - In addition to its role in neuronal survival, the brain neurotrophic factor
      (BDNF) has been shown to influence serotonin transmission and synaptic
      plasticity, events strongly implicated in the appearance of l-DOPA-induced
      dyskinesia (LID), a motor complication occurring in parkinsonian patients after
      long-term treatment with the dopamine precursor. In order to evaluate a possible
      influence of BDNF in the appearance of LID, 6-OHDA-lesioned rats received a
      striatal injection of different concentrations of an adeno-associated viral (AAV)
      vector over-expressing either BDNF or GFP, as control vector. Eight weeks later,
      animals started to receive a daily treatment with l-DOPA (4-6mg/kg plus
      benserazide 4-6mg/kg, s.c.) or saline, and dyskinesias, as well as l-DOPA-induced
      rotations, were evaluated at several time-points. Moreover, molecular changes in
      striatal D1 receptor-dependent cAMP/PKA and ERK/mTORC signaling pathways, as well
      as, sprouting of striatal serotonin axons, were measured. Results showed that the
      AAV-BDNF vector injection induced striatal over-expression of BDNF, as well as
      striatal and pallidal serotonin axon hyperinnervation. Moreover, rats that over
      expressed BDNF were more prone to develop LID and l-DOPA-induced rotations,
      compared to the GFP-treated control group. Finally, rats that over-expressed BDNF
      showed increased levels of striatal D1R-dependent signaling phospho-proteins in
      response to l-DOPA administration. This study suggests that BDNF over-expression,
      by inducing changes in pre-synaptic serotonin axonal trophism, is able to
      exacerbate maladaptive responses to l-DOPA administration.

PMID- 28757260
TI  - Comparison between publicly accessible publications, registries, and protocols of
      phase III trials indicated persistence of selective outcome reporting.
AB  - OBJECTIVES: The decision to make protocols of phase III randomized controlled
      trials (RCTs) publicly accessible by leading journals was a landmark event in
      clinical trial reporting. Here, we compared primary outcomes defined in protocols
      with those in publications describing the trials and in trial registration. STUDY
      DESIGN AND SETTING: We identified phase III RCTs published between January 1,
      2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The
      Journal of the American Medical Association, and The BMJ with available
      protocols. Consistency in primary outcomes between protocols and registries
      (articles) was evaluated. RESULTS: We identified 299 phase III RCTs with
      available protocols in this analysis. Out of them, 25 trials (8.4%) had some
      discrepancy for primary outcomes between publications and protocols. Types of
      discrepancies included protocol-defined primary outcome reported as nonprimary
      outcome in publication (11 trials, 3.7%), protocol-defined primary outcome
      omitted in publication (10 trials, 3.3%), new primary outcome introduced in
      publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as
      primary outcome in publication (4 trials, 1.3%), and different timing of
      assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies
      in primary outcome, 15 trials (60.0%) had discrepancies that favored
      statistically significant results. Registration could be seen as a valid
      surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary
      outcome. CONCLUSION: Despite unrestricted public access to protocols, selective
      outcome reporting persists in a small fraction of phase III RCTs. Only studies
      from four leading journals were included, which may cause selection bias and
      limit the generalizability of this finding.

PMID- 28757261
TI  - Searching ClinicalTrials.gov did not change the conclusions of a systematic
      review.
AB  - OBJECTIVES: We assessed the effect of searching ClinicalTrials.gov on the
      conclusions of a systematic review. STUDY DESIGN AND SETTING: We conducted this
      case study concurrently with a systematic review. We searched ClinicalTrials.gov
      on March 9, 2016, to identify trial records eligible for inclusion in the review.
      Two independent reviewers screened ClinicalTrials.gov records. We compared
      conclusions and strength of evidence grade with and without ClinicalTrials.gov
      records for 31 comparisons and 2 outcomes. RESULTS: We identified 106 trials (53
      in the peer-reviewed literature only, 23 in ClinicalTrials.gov only, and 30 in
      both sources). For one comparison, the addition of results identified through
      ClinicalTrials.gov reduced the pooled effect size. We found evidence of selective
      outcome reporting for two comparisons and suspected publication bias for another
      two comparisons. For all other comparisons, searching ClinicalTrials.gov did not
      change conclusions or the strength of evidence grading for the two outcomes.
      CONCLUSION: Our search of ClinicalTrials.gov bolstered suspicions of reporting
      biases but did not change either the conclusions or the strength of evidence
      grading. Further research is needed to determine the effect of searching
      ClinicalTrials.gov on the conclusions of systematic reviews in different topic
      areas and as the new rules for registration of trial results take effect.

PMID- 28757262
TI  - Tofacitinib Is the Right OCTAVE for Ulcerative Colitis.

PMID- 28757259
TI  - Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral
      ischemia-reperfusion.
AB  - Post-ischemic neurodegeneration remains the principal cause of mortality
      following cardiac resuscitation. Recent studies have implicated gastrointestinal
      ischemia in the sepsis-like response associated with the post-cardiac arrest
      syndrome (PCAS). However, the extent to which the resulting low-grade endotoxemia
      present in up to 86% of resuscitated patients affects cerebral ischemia
      reperfusion injury has not been investigated. Here we report that a single
      injection of low-dose lipopolysaccharide (50MUg/kg, IP) delivered after global
      cerebral ischemia (GCI) induces blood-brain barrier permeability, microglial
      activation, cortical injury, and functional decline in vivo, compared to ischemia
      alone. And while GCI was sufficient to induce neutrophil (PMN) activation and
      recruitment to the post-ischemic CNS, minimal endotoxemia exhibited synergistic
      effects on markers of systemic inflammation including PMN priming, lung damage,
      and PMN burden within the lung and other non-ischemic organs including the kidney
      and liver. Our findings predict that acute interventions geared towards blocking
      the effects of serologically occult endotoxemia in survivors of cardiac arrest
      will limit delayed neurodegeneration, multi-organ dysfunction and potentially
      other features of PCAS. This work also introduces lung-brain coupling as a novel
      therapeutic target with broad effects on innate immune priming and post-ischemic
      neurodegeneration following cardiac arrest and related cerebrovascular
      conditions.

PMID- 28757266
TI  - Carving Out a Place for Endoscopic Submucosal Dissection.

PMID- 28757264
TI  - Baseline Parameters in Clinical Trials for Nonalcoholic Steatohepatitis:
      Recommendations From the Liver Forum.

PMID- 28757267
TI  - Chromoendoscopy versus White Light Endoscopy: Does it Matter?

PMID- 28757268
TI  - How to Give Feedback During Endoscopy Training.

PMID- 28757263
TI  - Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and
      Implications for Patients.
AB  - Esophageal squamous cell carcinoma (ESCC) is a common malignancy without
      effective therapy. The exomes of more than 600 ESCCs have been sequenced in the
      past 4 years, and numerous key aberrations have been identified. Recently,
      researchers reported both inter- and intratumor heterogeneity. Although these are
      interesting observations, their clinical implications are unclear due to the
      limited number of samples profiled. Epigenomic alterations, such as changes in
      DNA methylation, histone acetylation, and RNA editing, also have been observed in
      ESCCs. However, it is not clear what proportion of ESCC cells carry these
      epigenomic aberrations or how they contribute to tumor development. We review the
      genomic and epigenomic characteristics of ESCCs, with a focus on emerging themes.
      We discuss their clinical implications and future research directions.

PMID- 28757269
TI  - Proton Pump Inhibitors and Chronic Kidney Disease: Causation or Another False
      Alarm?

PMID- 28757265
TI  - Pathophysiology of Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis is an emerging disease that is distinguished from
      gastroesophageal reflux disease by the expression of a unique esophageal
      transcriptome and the interplay of early life environmental factors with distinct
      genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14). Rare genetic
      syndromes have uncovered the contribution of barrier disruption, mediated in part
      by defective desmosomes and dysregulated transforming growth factor beta
      production and signaling, to eosinophilic esophagitis pathophysiology.
      Experimental modeling has defined a cooperative role of activated eosinophils,
      mast cells, and the cytokines IL-5 and IL-13, mediated by allergic sensitization
      to multiple foods. Understanding these processes is opening the way to better
      treatment based on disrupting allergic inflammatory and type 2 cytokine-mediated
      responses, including anti-cytokine therapeutics and dietary therapy.

PMID- 28757270
TI  - Sugar, Sugar . . . Not So Sweet for the Liver.

PMID- 28757271
TI  - Public-Private Partnership: Targeting Real-World Data for Hepatitis C Direct
      Acting Antivirals.

PMID- 28757272
TI  - Epidemiology of dermatomycoses in Kerman province, southeast of Iran: A 10-years
      retrospective study (2004-2014).
AB  - OBJECTIVES: Superficial and cutaneous fungal infections (SCFIs) are an important
      public health problem and are common in tropical and subtropical countries.
      Pityriasis versicolor, dermatophytosis, erythrasma, onychomycosis, and otomycosis
      are the major diseases associated with SCFIs. The aim of this study was to
      evaluate the prevalence and causative agents of dermatomycoses over a period of
      10 years in Kerman province, southeast of Iran. METHODS: A number of 1782
      subjects, including 1096 females and 686 males, with cutaneous disorders in their
      skin, nail, and hair suspected to have SCFIs participated in this study. The
      collected specimens were examined using direct microscopy examination, staining,
      culture on specific media and PCR-RFLP technique. RESULTS: In total, 617 (34.62%)
      subjects had SCFIs, of whom 290 (47%) were female and 327 (53%) were male.
      Identified SCFIs included yeast infections, dermatophytosis, saprophyte
      onychomycosis, erythrasma, and otomycosis due to non-dermatophytic molds (NDMs).
      The highest prevalence of dermatomycoses was found among the 41-50-year and 31-40
      year age groups. Tinea unguium was the most common clinical pattern of
      dermatomycoses, and T. mentagrophytes was the predominant agent. Also,
      Aspergillus spp. were the most common NDMs agents of onychomycosis and
      otomycosis. CONCLUSIONS: This study summarized the epidemiological trends and
      etiologic agents of SCFIs in a 10-year period in Kerman, southeast of Iran.
      Consideration of the current epidemiologic trends in the prevalence and knowledge
      of the exact causative agents of SCFIs may play an important key role towards
      further investigations, diagnosis, and modification of current treatments.

PMID- 28757273
TI  - Immunomodulatory effect of photodynamic therapy in Galleria mellonella infected
      with Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is an important pathogen in the development of
      periodontal disease. Our study investigated if the treatment with antimicrobial
      photodynamic therapy (aPDT) that employs a nontoxic dye, followed by irradiation
      with harmless visible light can attenuate the experimental infection of P.
      gingivalis in Galleria mellonella. Firstly, different concentrations of P.
      gingivalis ranging from 102 to 106 cells/larva were injected into the animal to
      obtain a lethal concentration. Next, the following groups of G. mellonella
      infected with P. gingivalis were evaluated: inoculation of the photosensitizer
      and application of laser (P + L+), inoculation of physiologic solution and
      application of laser (P-L+), inoculation the photosensitizer without laser (P + L
      ) and inoculation of physiologic solution without Laser (P-L-). The effects of
      aPDT on infection by P. gingivalis were evaluated by survival curve analysis and
      hemocytes count. A lethal concentration of 106 cells/larva was adopted for
      evaluating the effects of aPDT on experimental infection with P. gingivalis. We
      found that after 120 s of PDT application, the death of G. mellonella was
      significantly lower compared to the control groups (p = 0.0010). Moreover, the
      hemocyte density in the P+L+ group was increased by 9.6 * 106 cells/mL (2.62-fold
      increase) compared to the infected larvae with no treatment (L-P- group) (p =
      0.0175). Finally, we verified that the aPDT led to a significant reduction of the
      number of P. gingivalis cells in G. mellonella hemolymph. In conclusion, PDT
      application was effective against P. gingivalis infection by increasing the
      survival of G. mellonella and was able to increase the circulating hemocytes
      indicating that PDT activates the G. mellonella immune system.

PMID- 28757274
TI  - Phenotypic and genotypic characterization of biofilm formation among
      Staphylococcus aureus isolates from clinical specimens, an Atomic Force
      Microscopic (AFM) study.
AB  - INTRODUCTION: Staphylococcus aureus is a major cause of nosocomial infections.
      Biofilm formation is an important factor for bacterial pathogenesis. Its
      mechanisms are complex and include of many genes depends on expression of icaADBC
      operon involved in the synthesis of a polysaccharide intercellular adhesion. AIM:
      The aim of study was to investigate biofilm forming ability of Staphylococcus
      aureus strains by phenotypic and genotypic methods. Also Atomic Force microscope
      (AFM) was used to visualize biofilm formation. METHODS: 140 Isolates were
      collected from clinical specimens of patients in Milad Hospital, Tehran and
      diagnosed by biochemical tests. The ability of strains to produce slime was
      evaluated by CRA method. For diagnosing of bacterial EPS, Indian ink staining
      were used and finally biofilm surface of 3 isolates observed by AFM. The
      prevalence of icaA and icaD genes was determined by PCR. RESULTS: By CRA method
      15% of samples considered as positive slime producers, 44.28% as intermediate and
      40.71% indicative as negative slime producers. 118 staphylococcus aureus strains
      showed a distinct halo transparent zone but 22 strains showed no halo zone. AFM
      analysis of Slime positive isolates showed a distinct and complete biofilm
      formation. In slime negative strain, there was not observed biofilm. The
      prevalence of icaA, icaD genes was 44.2% and 10% of the isolates had both genes
      simultaneously. CONCLUSION: There is a relationship between exopolysaccharide
      layer and biofilm formation of Staphylococcus aureus isolates. The presence of
      icaAD genes among isolates is not associated with in vitro formation of biofilm.
      AFM is a useful tool for observation of bacterial biofilm formation.

PMID- 28757275
TI  - Protective effects of sinomenine against LPS-induced inflammation in piglets.
AB  - The aim of this study was to investigate in piglets, the anti-endotoxin and anti
      inflammatory effects of sinomenine, an agent commonly found in Chinese herbal
      medicines. In high-, middle- and low-dose sinomenine groups, piglets were
      initially challenged with endotoxin (i.e., 1 mg lipopolysaccharide (LPS)/kg) by
      intraperitoneal (IP) injection and, 3 h later, intramuscularly (IM) with
      sinomenine at 1, 5, or 10 mg/kg. In a drug control group, piglets were dosed IP
      with vehicle and 3 h late IM with 10 mg/kg sinomenine while those in an LPS
      control group were challenged with 1 mg LPS/kg (IP) and then vehicle 3 h later;
      naive control piglets were administered normal saline IP and then IM only. At 12,
      24, and 48 h post-LPS/vehicle injection, blood samples were collected from the
      precaval vein of piglets. Clinical signs were recorded during the trial and index
      levels were analyzed by ELISA kits. The results revealed sinomenine could reduce
      the incidence/severity of certain LPS-induced toxicities, e.g., cell adhesion,
      systemic inflammation, and multiple organ dysfunction. Taken together, the data
      suggested to us that sinomenine might effectively be useful to regulate
      inflammatory responses as part of future anti-endotoxin therapies.

PMID- 28757276
TI  - Value of immunohistochemical expression of podocalyxin in active lupus nephritis.
AB  - : Podocalyxin is an electronegative sialoglycoprotein that prevents the podocyte
      foot process from collapsing. The aim of this study was to detect an association
      between the glomerular immunohistochemical (IHC) expression of podocalyxin and
      the degree of podocyte effacement detected by electron microscopy, and to
      evaluate the role of podocalyxin IHC expression as a novel marker for disease
      activity in lupus nephritis (LN). METHODS: Thirty-two renal biopsies of active
      lupus nephritis patients were studied. Clinical assessment by the systemic lupus
      activity measure (SLAM-R) score and laboratory data were included [serum
      creatinine, 24-h urinary protein, antinuclear antibodies (ANA), anti-double
      strand DNA antibodies (anti-dsDNA), C3 and C4]. Light (L/M) and electron
      microscopic (E/M) examination was conducted. Podocyte loss was evaluated by
      immunohistochemistry with monoclonal anti-podocalyxin antibodies by means of a
      semiquantitative score that was graded from 0 to 4+ according to the percentage
      of glomerular involvement. RESULTS: 22 cases (68.8%) with LN class IV, 6 (18.8%)
      with class III and 4 (12.5%) with class V. The mean age was (25.41+/-10.13)
      years. There was a significant negative correlation between IHC podocalyxin score
      and LN class, and NIH activity parameters such as leukocyte infiltration,
      endocapillary proliferation, fibrinoid necrosis and cellular crescent and disease
      activity index but not chronicity index. There was a highly significant negative
      correlation between IHC podocalyxin and podocyte effacement by E/M (rs=-0.903,
      P=0.000), and E/M immune deposits (r=-0.53, P=0.001), and a significant
      association with degree of proteinuria, ANA and SLAM score (P<0.05). CONCLUSIONS:
      Podocyte loss indicated by podocalyxin immunohistochemical expression reflects
      the degree of activity and severity of LN and the degree of podocyte effacement
      by E/M.

PMID- 28757277
TI  - Haemodiafiltration with ultrafiltrate regeneration in the removal of free light
      chains in multiple myeloma and acute kidney injury.

PMID- 28757278
TI  - Distribution and chronotropic effects of serotonin in the zebrafish heart.
AB  - Several lines of evidence suggest that serotonin (5-HT) has a regulatory role in
      cardiovascular function from embryogenesis through adulthood. However, the
      reported actions of 5-HT are often contradictory and include bradycardia or
      tachycardia, hypotension or hypertension, and vasodilation or vasoconstriction.
      Clarifying such cardiac effects requires further research and may benefit from
      utilizing a model simpler than the mammalian hearts traditionally used in these
      studies. In the present study, we describe the cardiac distribution and
      chronotropic responses of 5-HT in the zebrafish heart. A combined anatomical,
      electrophysiological, and pharmacological approach was used to investigate the
      involvement of 5-HT pathways, and to compare neural and direct myocardial
      pathways of biological action. Immunohistochemical methods revealed 5-HT in
      endocardial cells, glial-like cells, and intracardiac neurons in the atrium.
      Electrocardiogram (ECG) recordings combined with the administration of
      pharmacological agents demonstrated that 5-HT acted predominantly through direct
      myocardial pathways resulting in a reduction of heart rate. Overall, the results
      of this study contribute significant advances in the establishment of the
      zebrafish as a new model for studies of the role of 5-HT in autonomic cardiac
      control.

PMID- 28757279
TI  - Bacteremic pneumococcal pneumonia in adults.

PMID- 28757280
TI  - Bilateral elastofibroma dorsi: PET-CT findings.

PMID- 28757281
TI  - Bronchiectasis and Azithromycin.

PMID- 28757282
TI  - Unilateral lung infiltrate: A rare form of presentation of primary pulmonary
      lymphoma.

PMID- 28757283
TI  - What's New in Idiopathic Pulmonary Fibrosis?

PMID- 28757284
TI  - Changes in the Profile of Diseases Caused by the Inhalation of Silica.

PMID- 28757285
TI  - Proposal of a New Adverse Event Classification by the Society of Interventional
      Radiology Standards of Practice Committee.
AB  - PURPOSE: To develop a new adverse event (AE) classification for the
      interventional radiology (IR) procedures and evaluate its clinical, research, and
      educational value compared with the existing Society of Interventional Radiology
      (SIR) classification via an SIR member survey. MATERIALS AND METHODS: A new AE
      classification was developed by members of the Standards of Practice Committee of
      the SIR. Subsequently, a survey was created by a group of 18 members from the SIR
      Standards of Practice Committee and Service Lines. Twelve clinical AE case
      scenarios were generated that encompassed a broad spectrum of IR procedures and
      potential AEs. Survey questions were designed to evaluate the following domains:
      educational and research values, accountability for intraprocedural challenges,
      consistency of AE reporting, unambiguity, and potential for incorporation into
      existing quality-assurance framework. For each AE scenario, the survey
      participants were instructed to answer questions about the proposed and existing
      SIR classifications. SIR members were invited via online survey links, and 68
      members participated among 140 surveyed. Answers on new and existing
      classifications were evaluated and compared statistically. Overall comparison
      between the two surveys was performed by generalized linear modeling. RESULTS:
      The proposed AE classification received superior evaluations in terms of
      consistency of reporting (P < .05) and potential for incorporation into existing
      quality-assurance framework (P < .05). Respondents gave a higher overall rating
      to the educational and research value of the new compared with the existing
      classification (P < .05). CONCLUSIONS: This study proposed an AE classification
      system that outperformed the existing SIR classification in the studied domains.

PMID- 28757286
TI  - Transradial versus Transfemoral Access for Hepatic Chemoembolization:
      Intrapatient Prospective Single-Center Study.
AB  - PURPOSE: To compare transfemoral approach (TFA) and transradial approach (TRA) in
      patients undergoing hepatic chemoembolization in terms of safety, feasibility,
      and procedural variables, including fluoroscopy time, radiation dose (reference
      air kerma [RAK]), and patient preference. MATERIALS AND METHODS: A single-center
      prospective intrapatient comparative study was conducted with 42 consecutive
      patients with hepatic malignancies who received 2 consecutive treatment sessions
      of unilobar hepatic chemoembolization within a 4-week interval over a 6-month
      period with both TRA and TFA. All procedures were performed by 1 interventional
      radiologist who assessed the eligibility of patients for inclusion in the study.
      The primary endpoint was intraprocedural conversion rate. Secondary endpoints
      were access site complications, angiographic and procedural variables, and
      evaluation of patient discomfort and preferences. RESULTS: A 100% technical
      success rate and a crossover rate of 0% were recorded. There were no major
      vascular complications and similar rates of minor complications (4.8% for TRA,
      7.1% for TFA; P = .095), which were self-limited and without any clinical
      sequelae. TRA treatments required a significantly longer preparation time for the
      procedure (P = .008) with no significant differences for other procedural
      variables. Greater discomfort at the access route and patient inability to
      perform basic activities after the procedure were recorded for TFA (P < .001).
      TRA was preferred by 35 patients (35/42) for potential future transarterial
      procedures. CONCLUSIONS: TRA is safe and feasible for transarterial hepatic
      chemoembolization, with high technical success, low overall complications, and
      improved patient comfort.

PMID- 28757287
TI  - Sagittal lumbopelvic alignment in patients with low back pain and the effects of
      a high-load lifting exercise and individualized low-load motor control exercises
      a randomized controlled trial.
AB  - BACKGROUND CONTEXT: Assessment of posture and lumbopelvic alignment is often the
      main focus in the classification and treatment of patients with low back pain
      (LBP). However, little is known regarding the effects of motor control
      interventions on objective measures of lumbopelvic alignment. PURPOSE: The
      primary aim of this study was to describe the variation of sagittal lumbopelvic
      alignment in patients with nociceptive mechanical LBP. The secondary aim was to
      compare the effects of a high-load lifting exercise (HLL) and low-load motor
      control exercises (LMC) on the change in lumbopelvic alignment with a special
      emphasis on patients with high and low degrees of lumbar lordosis (lu) and sacral
      angle (sa). STUDY DESIGN: This study is a secondary analysis of a randomized
      controlled trial evaluating the effects of HLL and LMC. PATIENT SAMPLE: Patients
      from the primary study, that is, patients categorized with nociceptive mechanical
      LBP, who agreed to participate in the radiographic examination were included
      (n=66). OUTCOME MEASURES: Lateral plain radiographic images were used to evaluate
      lumbopelvic alignment regarding the lumbar lordosis and the sacral angle as
      outcomes, with posterior bend as an explanatory variable. MATERIALS AND METHODS:
      The participants were recruited to the study from two occupational health-care
      facilities. They were randomized to either the HLL or the LMC intervention group
      and offered 12 supervised exercise sessions. Outcome measures were collected at
      baseline and following the end of intervention period 2 months after baseline.
      Between- and within-group analyses of intervention groups and subgroups based on
      the distribution of the baseline values for the lumbar lordosis and the sacral
      angle, respectively (LOW, MID, and HIGH), were performed using both parametric
      and non-parametric statistics. RESULTS: The ranges of values for the present
      sample were 26.9-91.6 degrees  (M=59.0 degrees , standard deviation [SD]=11.5
      degrees ) for the lumbar lordosis and 18.2-72.1 degrees  (M=42.0 degrees , SD=9.6
      degrees ) for the sacral angle. There were no significant differences between the
      intervention groups in the percent change of eitheroutcome measure. Neither did
      any outcome change significantly over time within the intervention groups. In the
      subgroups, based on the distribution of respective baseline values, LOWlu showed
      a significantly increased lumbar lordosis, whereas HIGHsa showed a significantly
      decreased sacral angle following intervention. CONCLUSIONS: This study describes
      the wide distribution of values for lumbopelvic alignment for patients with
      nociceptive mechanical LBP. Further research is needed to investigate subgroups
      of other types of LBP and contrast findings to those presented in this study. Our
      results also suggest that retraining of the lumbopelvic alignment could be
      possible for patients with LBP.

PMID- 28757288
TI  - High-level secretion and characterization of cyclodextrin glycosyltransferase in
      recombinant Komagataella phaffii.
AB  - Cyclodextrin glycosyltransferase (CGTase) catalyzes the conversion of starch into
      cyclodextrin (CD), which is widely applied in food, pharmaceutical, cosmetic, and
      agricultural industries. For efficient production of CD, high yield of CGTase
      with good characteristics is necessary. In this study, the cgt gene from Bacillus
      pseudalcaliphilus was expressed in Komagataella phaffii after codon optimization
      and expression vector selection. The beta-CGTase activity in the transformant
      reached 3885.1UmL-1, which is the highest value reported so far, at 28 degrees C,
      6% inoculum ratio, and 1.5% methanol addition following 24h of incubation. The
      recombinant CGTase showed high specific activity at 80 degrees C without any
      gamma-CGTase activity, and had good stability in a wide pH and temperature range.
      These results demonstrate that the recombinant CGTase could have potential
      industrial applications.

PMID- 28757289
TI  - Workflows for microscopy image analysis and cellular phenotyping.
AB  - In large scale biological experiments, like high-throughput or high-content
      cellular screening, the amount and the complexity of images to be analyzed are
      steadily increasing. To handle and process these images, well defined image
      processing and analysis steps need to be performed by applying dedicated
      workflows. Multiple software tools have emerged with the aim to facilitate
      creation of such workflows by integrating existing methods, tools, and routines,
      and by adapting them to different applications and questions, as well as making
      them reusable and interchangeable. In this review, we describe workflow systems
      for the integration of microscopy image analysis techniques with focus on KNIME
      and Galaxy.

PMID- 28757290
TI  - KNIME for reproducible cross-domain analysis of life science data.
AB  - Experiments in the life sciences often involve tools from a variety of domains
      such as mass spectrometry, next generation sequencing, or image processing.
      Passing the data between those tools often involves complex scripts for
      controlling data flow, data transformation, and statistical analysis. Such
      scripts are not only prone to be platform dependent, they also tend to grow as
      the experiment progresses and are seldomly well documented, a fact that hinders
      the reproducibility of the experiment. Workflow systems such as KNIME Analytics
      Platform aim to solve these problems by providing a platform for connecting tools
      graphically and guaranteeing the same results on different operating systems. As
      an open source software, KNIME allows scientists and programmers to provide their
      own extensions to the scientific community. In this review paper we present
      selected extensions from the life sciences that simplify data exploration,
      analysis, and visualization and are interoperable due to KNIME's unified data
      model. Additionally, we name other workflow systems that are commonly used in the
      life sciences and highlight their similarities and differences to KNIME.

PMID- 28757291
TI  - Protein aggregation, cardiovascular diseases, and exercise training: Where do we
      stand?
AB  - Cells ensure their protein quality control through the proteostasis network.
      Aging and age-related diseases, such as neurodegenerative and cardiovascular
      diseases, have been associated to the reduction of proteostasis network
      efficiency and, consequently, to the accumulation of protein misfolded
      aggregates. The decline in protein homeostasis has been associated with the
      development and progression of atherosclerotic cardiovascular disease, cardiac
      hypertrophy, cardiomyopathies, and heart failure. Exercise training is a key
      component of the management of patients with cardiovascular disease, consistently
      improving quality of life and prognosis. In this review, we give an overview on
      age-related protein aggregation, the role of the increase of misfolded protein
      aggregates on cardiovascular pathophysiology, and describe the beneficial or
      deleterious effects of the proteostasis network on the development of
      cardiovascular disease. We subsequently discuss how exercise training, a key
      lifestyle intervention in those with cardiovascular disease, could restore
      proteostasis and improve disease status.

PMID- 28757292
TI  - Is Ebola a sexually transmitted disease? Implication of Ebola RNA persistence in
      the semen.

PMID- 28757293
TI  - Economic cost and burden of dengue during epidemics and non-epidemic years in
      Taiwan.
AB  - BACKGROUND: Determining the disease and economic burden of dengue is critical for
      the allocation of public health resources. Several studies have used disability
      adjusted life-years (DALYs) to estimate the disease burden of dengue in different
      regions. However, there are no published studies discussing the estimates of
      dengue-related economic and disease burden specifically in Taiwan. OBJECTIVES: We
      assessed the economic cost and disease burden of dengue infections in Taiwan for
      the period 1998-2014, and compared these during epidemic and non-epidemic years.
      METHODS: We estimated the annual DALYs per million population using the
      disability weights for dengue fever (DF), dengue hemorrhagic fever (DHF), dengue
      shock syndrome (DSS), and death cases. Economic costs were estimated and divided
      into direct (medical costs) and indirect costs (lost work days and caregiver
      fees). RESULTS: For the period 1998-2014, a mean of 115.3 (range: 6.3-934.3)
      DALYs per million population annually were lost to dengue. In epidemic years,
      direct costs associated with dengue resulted mostly from hospitalization
      (86.09%), emergency (7.77%), outpatient (6.10%), and drug costs (0.03%). For
      indirect costs, lost productivity due to death (70.76%) was the dominant
      contributor. Overall, the costs were 12.3 times higher in epidemic years than in
      non-epidemic years (Wilcoxon rank sum test, p<0.05). CONCLUSIONS: This study is
      the first to evaluate the economic costs and disease burden of dengue infections
      for this period in Taiwan, and reveals significant differences in economic impact
      between epidemic and non-epidemic years.

PMID- 28757294
TI  - Increasing evidence of potential toxicity of a common antibiotic combination.

PMID- 28757295
TI  - When has it been studied about La Crosse Virus?: Bibliometric analysis of world
      scientific production.

PMID- 28757296
TI  - Chickenpox outbreak in Faisalabad: A lesson for the future.

PMID- 28757297
TI  - Haemophilus influenzae type b meningitis in a vaccinated and immunocompetent
      child.

PMID- 28757298
TI  - Arbovirus surveillance in Honduras: Are true representations of disease trends
      possible?

PMID- 28757300
TI  - Tuberculosis controlling, from China's perspective.

PMID- 28757299
TI  - The incidence of subclinical forms of urogenital tuberculosis in patients with
      pulmonary tuberculosis.
AB  - The aim of our study was to determine whether patients with pulmonary
      tuberculosis may have subclinical forms of urogenital tuberculosis. Between 2011
      and 2012, a prospective study was conducted. Basic demographic parameters were
      recorded and the following investigations were performed: direct bacilloscopy of
      sputum, evaluation of affected lung fields and presence of cavities on chest X
      ray, Mantoux tuberculin skin test II, and interferon gamma release assay. Culture
      and molecular methods for Mycobacterium tuberculosis in urine were performed. In
      cases with a positive urine test, an ultrasound examination, computed tomography
      scan of the abdomen, and endoscopy of the urinary tract were performed. A total
      of 102 patients (75 men and 27 women) were included in the study, with a median
      age of 46.8 years. Subclinical forms of urogenital TB were detected in 7
      patients; 5 by molecular methods, 1 by urine culture, and 1 with both methods The
      presence of subclinical forms of genitourinary TB was found in 4 patients without
      and 3 patients with findings on imaging methods corresponding to TB. A
      significant number of patients with pulmonary tuberculosis may simultaneously
      have subclinical forms of urogenital TB.

PMID- 28757302
TI  - "I've just never gotten around to doing it": Men's approaches to managing BRCA
      related cancer risks.
AB  - OBJECTIVE: To examine men's approaches to managing BRCA-related cancer risks.
      METHODS: 25 Qualitative interviews were conducted with men who are at risk for
      BRCA-related cancers. Thematic analysis was conducted using the constant
      comparison. RESULTS: Qualitative analysis revealed two different approaches for
      how men managed their BRCA-related cancer risks. Men were engaged when: (1)
      initially seeking information, (2) uptake of genetic testing, and (3) population
      screening procedures. Men were passively avoidant for: (1) follow-up information
      seeking, (2) uptake of genetic testing, and (3) BRCA-specific screening. Men's
      justifications for engaged risk management were to: (1) protect their family, (2)
      respond to encouragement from others, and (3) get knowledge for themselves. Their
      justifications for passively avoidant management were due to: (1) limited access
      to clear risk information, (2) little fear of cancer development, (3) barriers to
      testing/screening, and (4) reliance on incomplete illness representations.
      CONCLUSIONS: Men at risk for developing BRCA-related cancers approached risk
      management by primarily using a passive avoidance approach. That approach should
      be interpreted in context with the inconsistent information available to them,
      and the minimal NCCN guidelines for their risk surveillance. PRACTICE
      IMPLICATIONS: Findings may assist healthcare providers and family members in
      helping men manage their BRCA-related cancer risks.

PMID- 28757301
TI  - Quality of Life Outcomes after Primary Treatment for Clinically Localised
      Prostate Cancer: A Systematic Review.
AB  - CONTEXT: Current evidence-based management for clinically localised prostate
      cancer includes active surveillance, surgery, external beam radiotherapy (EBRT)
      and brachytherapy. The impact of these treatment modalities on quality of life
      (QoL) is uncertain. OBJECTIVE: To systematically review comparative studies
      investigating disease-specific QoL outcomes as assessed by validated cancer
      specific patient-reported outcome measures with at least 1 yr of follow-up after
      primary treatment for clinically localised prostate cancer. EVIDENCE ACQUISITION:
      MEDLINE, EMBASE, AMED, PsycINFO, and Cochrane Library were searched to identify
      relevant studies. Studies were critically appraised for the risk of bias. A
      narrative synthesis was undertaken. EVIDENCE SYNTHESIS: Of 11486 articles
      identified, 18 studies were eligible for inclusion, including three randomised
      controlled trials (RCTs; follow-up range: 60-72 mo) and 15 nonrandomised
      comparative studies (follow-up range: 12-180 mo) recruiting a total of 13604
      patients. Two RCTs recruited small cohorts and only one was judged to have a low
      risk of bias. The quality of evidence from observational studies was low to
      moderate. For a follow-up of up to 6 yr, active surveillance was found to have
      the lowest impact on cancer-specific QoL, surgery had a negative impact on
      urinary and sexual function when compared with active surveillance and EBRT, and
      EBRT had a negative impact on bowel function when compared with active
      surveillance and surgery. Data from one small RCT reported that brachytherapy has
      a negative impact on urinary function 1 yr post-treatment, but no significant
      urinary toxicity was reported at 5 yr. CONCLUSIONS: This is the first systematic
      review comparing the impact of different primary treatments on cancer-specific
      QoL for men with clinically localised prostate cancer, using validated cancer
      specific patient-reported outcome measures only. There is robust evidence that
      choice of primary treatment for localised prostate cancer has distinct impacts on
      patients' QoL. This should be discussed in detail with patients during
      pretreatment counselling. PATIENT SUMMARY: Our review of the current evidence
      suggests that for a period of up to 6 yr after treatment, men with localised
      prostate cancer who were managed with active surveillance reported high levels of
      quality of life (QoL). Men treated with surgery reported mainly urinary and
      sexual problems, while those treated with external beam radiotherapy reported
      mainly bowel problems. Men eligible for brachytherapy reported urinary problems
      up to a year after therapy, but then their QoL returned gradually to as it was
      before treatment.

PMID- 28757303
TI  - Risk accuracy of type 2 diabetes in middle aged adults: Associations with
      sociodemographic, clinical, psychological and behavioural factors.
AB  - OBJECTIVE: To identify the proportion of individuals with an accurate perception
      of their risk of type 2 diabetes (T2D) prior to, immediately after and eight
      weeks after receiving a personalised risk estimate. Additionally, we aimed to
      explore what factors are associated with underestimation and overestimation
      immediately post-intervention. METHODS: Cohort study based on the data collected
      in the Diabetes Risk Communication Trial. We included 379 participants (mean age
      48.9 (SD 7.4) years; 55.1% women) who received a genotypic or phenotypic risk
      estimate for T2D. RESULTS: While only 1.3% of participants perceived their risk
      accurately at baseline, this increased to 24.7% immediately after receiving a
      risk estimate and then dropped to 7.3% at eight weeks. Those who overestimated
      their risk at baseline continued to overestimate it, whereas those who
      underestimated their risk at baseline improved their risk accuracy. We did not
      identify any other characteristics associated with underestimation or
      overestimation immediately after receiving a risk estimate. CONCLUSION:
      Understanding a received risk estimate is challenging for most participants with
      many continuing to have inaccurate risk perception after receiving the estimate.
      PRACTICE IMPLICATIONS: Individuals who overestimate or underestimate their T2D
      risk before receiving risk information might require different approaches for
      altering their risk perception.

PMID- 28757304
TI  - Social Control of Hypothalamus-Mediated Male Aggression.
AB  - How environmental and physiological signals interact to influence neural circuits
      underlying developmentally programmed social interactions such as male
      territorial aggression is poorly understood. We have tested the influence of
      sensory cues, social context, and sex hormones on progesterone receptor (PR)
      expressing neurons in the ventromedial hypothalamus (VMH) that are critical for
      male territorial aggression. We find that these neurons can drive aggressive
      displays in solitary males independent of pheromonal input, gonadal hormones,
      opponents, or social context. By contrast, these neurons cannot elicit aggression
      in socially housed males that intrude in another male's territory unless their
      pheromone-sensing is disabled. This modulation of aggression cannot be accounted
      for by linear integration of environmental and physiological signals. Together,
      our studies suggest that fundamentally non-linear computations enable social
      context to exert a dominant influence on developmentally hard-wired hypothalamus
      mediated male territorial aggression.

PMID- 28757306
TI  - Functional Subpopulations of Neurons in a Macaque Face Patch Revealed by Single
      Unit fMRI Mapping.
AB  - Neurons within fMRI-defined face patches of the macaque brain exhibit shared
      categorical responses to flashed images but diverge in their responses under more
      natural viewing conditions. Here we investigate functional diversity among
      neurons in the anterior fundus (AF) face patch, combining whole-brain fMRI with
      longitudinal single-unit recordings in a local population (<1 mm3). For each
      cell, we computed a whole-brain correlation map based on its shared time course
      with voxels throughout the brain during naturalistic movie viewing. Based on this
      mapping, neighboring neurons showed markedly different affiliation with distant
      visually responsive areas and fell coarsely into subpopulations. Of these, only
      one subpopulation (~16% of neurons) yielded similar correlation maps to the local
      fMRI signal. The results employ the readout of large-scale fMRI networks and, by
      indicating multiple functional domains within a single voxel, present a new view
      of functional diversity within a local neural population.

PMID- 28757305
TI  - Precision Functional Mapping of Individual Human Brains.
AB  - Human functional MRI (fMRI) research primarily focuses on analyzing data averaged
      across groups, which limits the detail, specificity, and clinical utility of fMRI
      resting-state functional connectivity (RSFC) and task-activation maps. To push
      our understanding of functional brain organization to the level of individual
      humans, we assembled a novel MRI dataset containing 5 hr of RSFC data, 6 hr of
      task fMRI, multiple structural MRIs, and neuropsychological tests from each of
      ten adults. Using these data, we generated ten high-fidelity, individual-specific
      functional connectomes. This individual-connectome approach revealed several new
      types of spatial and organizational variability in brain networks, including
      unique network features and topologies that corresponded with structural and task
      derived brain features. We are releasing this highly sampled, individual-focused
      dataset as a resource for neuroscientists, and we propose precision individual
      connectomics as a model for future work examining the organization of healthy and
      diseased individual human brains.

PMID- 28757308
TI  - Scheduling primary care appointments online: Differences in availability based on
      health insurance.
AB  - BACKGROUND: Digital platforms that allow patients to go online or use smartphone
      applications to view and schedule physician appointments have not been well
      evaluated. METHODS: We conducted systematic searches for primary care physician
      appointments in 20 cities using ZocDoc, an online appointment scheduling
      platform. Availability was determined for three insurance types (self-pay,
      Medicare, and Medicaid) in states with and without Medicaid expansion. We
      collected data on physician characteristics, number of appointments available,
      and distance to clinics. RESULTS: The sample comprised 4150 physician
      observations across 17 states. Overall, the mean distance to clinic was 8.9 miles
      (SD: 8.4 miles), mean total number of appointments available within 3 days for
      the 10 closest physicians was 20.1 (SD: 27.1), and the mean number of physicians
      available within 5 miles was 5.4 (SD: 6.6). There were no differences in
      physician characteristics by insurance type. Access to appointments did not
      differ between Medicare and self-pay. However, compared to self-pay, appointments
      for Medicaid were further away (Mean difference in miles: 5.4, P < 0.001), and
      there were fewer physicians available within 5 miles (Mean difference in # of
      physicians: -4.9, P < 0.001). States that did not adopt Medicaid expansion had
      fewer appointments within proximity, but this differed similarly across insurance
      types. CONCLUSIONS: There were a substantial number of available appointments at
      close distances. However, Medicaid patients had less access to appointments
      within proximity than self-pay or Medicare patients.

PMID- 28757307
TI  - Association between oxidative stress and atrial fibrillation.
AB  - BACKGROUND: Oxidative stress (OS) may be a key mechanism underlying the
      development of atrial fibrillation (AF) in experimental studies, but data in
      humans remain limited. OBJECTIVE: Systemic OS can be estimated by measurements of
      circulating levels of the aminothiols including glutathione, cysteine, and their
      oxidized products. We tested the hypothesis that the redox potentials of
      glutathione (EhGSH) and cysteine will be associated with prevalent and incident
      AF. METHODS: Plasma levels of aminothiols were measured in 1439 patients
      undergoing coronary angiography, of whom 148 (10.3%) had a diagnosis of AF. After
      a median follow-up of 6.3 years, 104 of 917 patients (11.5%) developed incident
      AF. Multivariate logistic regression and Cox regression models were used to
      determine whether OS markers were independent predictors of prevalent and
      incident AF after adjustment for traditional risk factors, heart failure,
      coronary artery disease, and high-sensitivity C-reactive protein level. RESULTS:
      For each 10% increase in EhGSH, the odds of prevalent AF was 30% higher (odds
      ratio [OR] 1.3; 95% confidence interval [CI] 1.1-1.7; P = .02) and 90% higher (OR
      1.9; 95% CI 1.3-2.7; P = .004) when the median was used as a cutoff. The EhGSH
      level above the median was more predictive of chronic AF (OR 4.0; 95% CI 1.3
      12.9; P = .01) than of paroxysmal AF (OR 1.7; 95% CI 1.1-2.7; P = .03). Each 10%
      increase in EhGSH level was associated with a 40% increase in the risk of
      incident AF (hazard ratio 1.4; 95% CI 1.1-1.7; P = .01). CONCLUSION: Increased OS
      measured by the redox potentials of glutathione is associated with prevalent and
      incident AF. Therapies that modulate OS need to be investigated to treat and
      prevent AF.

PMID- 28757309
TI  - Reliability and Clinical Correlation of Transcranial Doppler Ultrasound in Sturge
      Weber Syndrome.
AB  - BACKGROUND: The reproducibility of transcranial Doppler (TCD) ultrasound
      measurements in Sturge-Weber syndrome (SWS) and TCD's ability to predict
      neurological progression is unknown. METHODS: In 14 individuals with SWS, TCD
      measured mean flow velocity, pulsatility index, peak systolic velocity, and end
      diastolic velocity in the middle, posterior, and anterior cerebral arteries of
      the affected and unaffected hemisphere. TCD was performed either once (n = 5) or
      twice in one day (n = 9). We assessed the reproducibility of the measurements
      performed twice on the same day on subjects and compared the TCD measurements to
      previously published age-matched controls. Clinically obtained neuroimaging was
      scored for extent and severity of SWS brain involvement. Patients were
      prospectively assigned SWS neuroscores. RESULTS: Middle cerebral artery velocity
      (r = 0.79, P = 0.04, n = 7), posterior cerebral artery velocity (r = 0.90, P =
      0.04, n = 5), and anterior cerebral artery pulsatility index (r = 0.82, P = 0.02,
      n = 7) were reproducible TCD measurements comparing same-day percent side-to-side
      differences. In subjects with SWS, affected and unaffected mean peak systolic
      velocity and end-diastolic velocity in the middle, posterior, and anterior
      cerebral arteries were globally lower compared with age-matched control subjects.
      Subjects with the lowest affected middle cerebral artery velocity had the
      greatest worsening in the total neurological score between time 1 and 2 (r = 
      0.73, P = 0.04, n = 8) and the most severe magnetic resonance imaging involvement
      of the affected frontal lobe (r = -0.82, P = 0.007, n = 9). CONCLUSIONS: TCD may
      be a reliable measure with potential clinical value, indicating that blood flow
      may be globally decreased in SWS patients with unilateral brain involvement.

PMID- 28757310
TI  - Recommendations for harmonization of data collection and analysis of
      developmental neurotoxicity endpoints in regulatory guideline studies:
      Proceedings of workshops presented at Society of Toxicology and joint Teratology
      Society and Neurobehavioral Teratology Society meetings.
AB  - The potential for developmental neurotoxicity (DNT) of environmental chemicals
      may be evaluated using specific test guidelines from the US Environmental
      Protection Agency or the Organisation for Economic Cooperation and Development
      (OECD). These guidelines generate neurobehavioral, neuropathological, and
      morphometric data that are evaluated by regulatory agencies globally. Data from
      these DNT guideline studies, or the more recent OECD extended one-generation
      reproductive toxicity guideline, play a pivotal role in children's health risk
      assessment in different world areas. Data from the same study may be interpreted
      differently by regulatory authorities in different countries resulting in
      inconsistent evaluations that may lead to inconsistencies in risk assessment
      decisions internationally, resulting in regional differences in public health
      protection or in commercial trade barriers. These issues of data interpretation
      and reporting are also relevant to juvenile and pre-postnatal studies conducted
      more routinely for pharmaceuticals and veterinary medicines. There is a need for
      development of recommendations geared toward the operational needs of the
      regulatory scientific reviewers who apply these studies in risk assessments, as
      well as the scientists who generate DNT data sets. The workshops summarized here
      draw upon the experience of the authors representing government, industry,
      contract research organizations, and academia to discuss the scientific issues
      that have emerged from diverse regulatory evaluations. Although various
      regulatory bodies have different risk management decisions and labeling
      requirements that are difficult to harmonize, the workshops provided an
      opportunity to work toward more harmonized scientific approaches for evaluating
      DNT data within the context of different regulatory frameworks. Five speakers and
      their coauthors with neurotoxicology, neuropathology, and regulatory toxicology
      expertise discussed issues of variability, data reporting and analysis, and
      expectations in DNT data that are encountered by regulatory authorities. In
      addition, principles for harmonized evaluation of data were suggested using
      guideline DNT data as case studies.

PMID- 28757311
TI  - Impacts of maternal diet and exercise on offspring behavior and body weights.
AB  - Human and animal studies indicate that maternal obesity can negatively impact
      aspects of metabolism and neurodevelopment in the offspring. Not known, however,
      is whether maternal exercise can alter these adverse outcomes. In this study,
      Long-Evans female rats were provided a high fat (60%; HFD) or control diet (CD)
      44days before mating and throughout gestation and lactation. Running wheels were
      available to half of each diet group during the gestational period only,
      resulting in four conditions: CD diet with (CDRW) or without (sedentary; CDSED)
      exercise, and HFD with (HFRW) or without (HFSED) exercise. Only male offspring
      (one per litter) were available for this study: they were put on control diet two
      weeks after weaning and examined using behavioral evaluations up to four months
      of age. Before weaning, offspring of CDRW dams weighed less than offspring from
      CDSED or HFD dams. After weaning, the lower weight in CDRW offspring generally
      persisted. Adult offspring from HFSED dams performed worse than the HFRW group in
      a Morris water maze during initial spatial training as well as reversal learning;
      memory was not impacted. No differences between groups were seen in tests of
      novel object recognition, social approach, or chocolate milk preference. Thus,
      maternal diet and exercise produced differential effects on body weights and
      cognitive behaviors in the offspring, and the data demonstrate a positive impact
      of maternal exercise on the offspring in that it ameliorated some deleterious
      behavioral effects of a maternal high fat diet.

PMID- 28757312
TI  - High paternal testosterone may protect against postpartum depressive symptoms in
      fathers, but confer risk to mothers and children.
AB  - Following the birth of an infant, decreases in testosterone and increases in
      depressive symptoms have been observed in fathers. Paternal testosterone may
      reflect fathers' investment in pair-bonding and paternal caregiving and, as such,
      may be associated with maternal and familial well-being. This study tests
      associations between paternal testosterone, paternal and maternal postpartum
      depressive symptoms, and subsequent family functioning. Within 149 couples,
      fathers provided testosterone samples when infants were approximately nine months
      old and both parents reported on postpartum depressive symptoms at two, nine, and
      15months postpartum. Fathers with lower aggregate testosterone reported more
      depressive symptoms at two and nine months postpartum. Mothers whose partners had
      higher evening testosterone reported more depressive symptoms at nine and
      15months postpartum. Maternal relationship satisfaction mediated this effect,
      such that mothers with higher testosterone partners reported more relationship
      dissatisfaction, which in turn predicted more maternal depressive symptoms.
      Higher paternal testosterone and paternal depressive symptoms at nine months
      postpartum each independently predicted greater fathering stress at 15months
      postpartum. Higher paternal testosterone also predicted more mother-reported
      intimate partner aggression at 15months postpartum. In addition to linear
      relationships between testosterone and depression, curvilinear relationships
      emerged such that fathers with both low and high testosterone at nine months
      postpartum reported more subsequent (15-month) depressive symptoms and fathering
      stress. In conclusion, whereas higher paternal testosterone may protect against
      paternal depression, it contributed to maternal distress and suboptimal family
      outcomes in our sample. Interventions that supplement or alter men's testosterone
      may have unintended consequences for family well-being.

PMID- 28757313
TI  - Within-subject effects and the social habituation function of oxytocin.

PMID- 28757314
TI  - Using Ion Torrent sequencing to study genetic mutation profiles of fatal thyroid
      cancers.
AB  - BACKGROUND/PURPOSE: Surgery followed by radioiodine is a mainstay of treatment
      for thyroid cancers of follicular origins. However, about 5% of the thyroid
      cancers are non-operable and/or radioiodine-refractory diseases, which are either
      locally advanced or metastatic and result in a survival of less than 5 years. How
      to treat this population of thyroid cancer patients becomes a critical issue
      requiring further understanding of the tumor's genetic information. METHODS: We
      used formalin-fixed paraffin-embedded specimens of 22 fatal thyroid cancers and
      their corresponding non-tumor parts, if available, to yield genomic DNA, and
      applied the Ion TorrentTM Personal Genome Machine (IT-PGM) System (Life
      Technologies), a next generation sequencing technology, to interrogate 740
      mutational hotspots in 46 oncogenes. We further validated the results by
      conventional direct sequencing. RESULTS: We confirmed 21 mutations of 11
      oncogenes in the 22 fatal thyroid cancer samples. Among them, the MET p.N375S and
      MLH1 p.V384D mutations, each was detected in two cases, and has rarely been found
      to be involved in thyroid cancer pathogenesis before. We also identified
      homozygous PDGFRA p.V824V mutation in eight out of the 22 cases, while the non
      tumor counterparts carried heterozygous PDGFRA p.V824V mutation. We noted that
      the Ion Torrent technique unfortunately showed high false positive rates for
      detecting EGFR mutations in thyroid cancers. CONCLUSION: The extensive genetic
      studies provide new insights to future targeted therapy in these patients. IT-PGM
      proved to be valuable for comprehensively searching genetic mutations in
      potentially fatal thyroid cancers.

PMID- 28757315
TI  - Liver transplant-related anastomotic biliary strictures: a novel, rapid, safe,
      radiation-sparing, and cost-effective management approach.
AB  - BACKGROUND AND AIMS: Biliary strictures after orthotopic liver transplantation
      (OLT) are typically managed by sequential ERCP procedures, with incremental
      dilation of the stricture and stent exchange (IDSE) and placement of new stents.
      This approach resolves >80% of strictures after 12 months but requires costly,
      lengthy ERCPs with significant patient radiation exposure. Increasing awareness
      of the harmful effects of radiation, escalating healthcare costs, and decreasing
      reimbursement for procedures mandate maximal efficiency in performing ERCP. We
      compared the traditional IDSE protocol with a sequential stent addition (SSA)
      protocol, in which additional stents are placed across the stricture during
      sequential ERCPs, without stent removal/exchange or stricture dilation. METHODS:
      Patients undergoing ERCP for OLT-related anastomotic strictures from 2010 to 2016
      were identified from a prospectively maintained endoscopy database. Procedure
      duration, fluoroscopy time, stricture resolution rates, adverse events, materials
      fees, and facility fees were analyzed for IDSE and SSA procedures. RESULTS:
      Seventy-seven patients underwent 277 IDSE and 132 SSA procedures. Mean
      fluoroscopy time was 64.5% shorter (P < .0001) and mean procedure duration 41.5%
      lower (P < .0001) with SSA compared with IDSE. SSA procedures required fewer
      accessory devices, resulting in significantly lower material (63.8%, P < .0001)
      and facility costs (42.8%, P < .0001) compared with IDSE. Stricture resolution
      was >95%, and low adverse event rates did not significantly differ. CONCLUSIONS:
      SSA results in shorter, cost-effective procedures requiring fewer accessory
      devices and exposing patients to less radiation. Stricture resolution rates are
      equivalent to IDSE, and adverse events do not differ significantly, even in this
      immunocompromised population.

PMID- 28757316
TI  - Increased detection of Barrett's esophagus-associated neoplasia using wide-area
      trans-epithelial sampling: a multicenter, prospective, randomized trial.
AB  - BACKGROUND AND AIMS: Wide-area transepithelial sampling (WATS) with computer
      assisted 3-dimensional analysis is a sampling technique that combines abrasive
      brushing of the Barrett's esophagus (BE) mucosa followed by neural network
      analysis to highlight abnormal-appearing cells. METHODS: We performed a
      randomized trial of referred BE patients undergoing surveillance at 16 medical
      centers. Subjects received either biopsy sampling followed by WATS or WATS
      followed by biopsy sampling. The primary outcome was rate of detection of high
      grade dysplasia/esophageal adenocarcinoma (HGD/EAC) using WATS in conjunction
      with biopsy sampling compared with biopsy sampling alone using standard
      histopathologic criteria. Secondary aims included evaluating neoplasia detection
      rates based on the procedure order (WATS vs biopsy sampling first), of each
      procedure separately, and the additional time required for WATS. RESULTS: One
      hundred sixty patients (mean age, 63.4 years; 76% men; 95% white) completed the
      trial. The median circumferential and maximal BE extents were 1.0 cm
      (interquartile range: .0-5.0) and 4.0 cm (interquartile range, 2.0-8.0),
      respectively. The diagnostic yield for biopsy sampling alone was as follows:
      HGD/EAC, 7 (4.4%); low-grade dysplasia (LGD), 28 (17.5%); nondysplastic BE
      (NDBE), 106 (66.25%); and no BE, 19 (11.9%). The addition of WATS to biopsy
      sampling yielded an additional 23 cases of HGD/EAC (absolute increase, 14.4%; 95%
      confidence interval, 7.5%-21.2%). Among these 23 patients, 11 were classified by
      biopsy sampling as NDBE and 12 as LGD/indefinite for dysplasia (IND); 14 received
      biopsy sampling first and 9 WATS first (not significant) and most (n = 21; 91.7%)
      had a prior dysplasia history. WATS added an average of 4.5 minutes to the
      procedure. CONCLUSION: Results of this multicenter, prospective, randomized trial
      demonstrate that the use of WATS in a referral BE population increases the
      detection of HGD/EAC. (Clinical trial registration number: NCT03008980.).

PMID- 28757317
TI  - Challenges in Ordering and Interpreting Pharmacogenomic Tests in Clinical
      Practice.

PMID- 28757318
TI  - New Treatment Option for Chronic Obstructive Pulmonary Disease: Two Long-Acting
      Bronchodilators in a Single Metered-Dose Inhaler.
AB  - Combination long-acting inhaled bronchodilators are central to the management of
      patients with moderate to very severe chronic obstructive pulmonary disease.
      Glycopyrrolate is a long-acting muscarinic antagonist (LAMA), and formoterol
      fumarate is a long-acting beta2 agonist (LABA). In randomized controlled trials,
      this LAMA/LABA combination in a metered-dose inhaler was shown to be effective in
      improving pulmonary function and quality of life. Clinicians now have the
      availability of 3 delivery systems for LAMA/LABA therapy, including metered-dose
      inhaler, dry-powder inhaler, and Soft Mist inhaler. On the basis of numerous
      patient factors, such as cognitive ability, manual strength/dexterity, and peak
      inspiratory flow, clinicians may select the most appropriate inhalation device.
      For each inhalation device, persistent patient education is absolutely essential,
      including observation of patient use. International evidence-based guidelines
      stress the critical importance of ensuring correct use of inhalation devices.

PMID- 28757319
TI  - Difficulties in Teaching Diagnostic Reasoning in the Digital Age: The Critical
      Role of the Teacher-Clinician Mentor.

PMID- 28757320
TI  - Restoring the Art of Medicine.

PMID- 28757321
TI  - Dueling Lungs: The Progression of Swyer-James Syndrome.

PMID- 28757322
TI  - Considerations on nonclinical approaches to modeling risk factors of suicidal
      ideation and behavior.
AB  - Given the serious nature of suicidal ideation and behavior (SIB) and the
      possibility of treatment-emergent SIB, pharmaceutical companies are now applying
      more proactive approaches in clinical trials and are considering the value of
      nonclinical models to predict SIB. The current review summarizes nonclinical
      approaches to modeling three common risk factors associated with SIB: aggression,
      impulsivity, and anhedonia. For each risk factor, a general description,
      advantages and disadvantages, species considerations, nonclinical to clinical
      translation, and pharmacological validation with respect to treatments associated
      with SIB are summarized. From this review, several gaps were identified that need
      to be addressed before use of these nonclinical models can be considered a viable
      option to predict the relative risk for SIB. Other future directions that may
      compliment these nonclinical approaches, including the use of selectively-bred or
      genetically-modified rodent models, transgenic models, gene expression profiling,
      and biomarker analysis, are discussed. This article was developed with the
      support of the DruSafe Leadership Group of the International Consortium for
      Innovation and Quality in Pharmaceutical Development (IQ, www.iqconsortium.org).

PMID- 28757323
TI  - Exogenous administration of mitochondrial DNA promotes ischemia reperfusion
      injury via TLR9-p38 MAPK pathway.
AB  - Previous studies have shown a role of mitochondrial DNA (mtDNA) in innate
      immunity. However, the specific role of mtDNA in acute myocardial infarction
      remains elusive. This study was designed to examine the damaging effect of mtDNA
      on cardiomyocytes. H9c2s cells were incubated with purified mtDNA or nuclear DNA
      with or without pretreatment by chloroquine, an inhibitor of Toll-like receptor
      9(TLR9). The cell viability was tested by MTT. To demonstrate the toxicity of
      mtDNA, mtDNA fragments were injected into rats 10 min before ischemia for 30 min
      and reperfusion for 24 h. Infarct size was measured by TTC staining. Apoptosis of
      myocardium was detected by TUNEL staining and caspase-3 activity. The levels of
      TLR9, p-p38 MAPK, and p38 MAPK were detected by western blotting. The results
      showed that exogenous mtDNA reduced the viability of H9c2s cells and induced TLR9
      expression, caspase 3 activation and p38 mitogen-activated protein kinase (MAPK)
      phosphorylation. However, these effects were inhibited by chloroquine. In
      contrast, nuclear DNA did not have these effects. Intravenous injection of mtDNA
      into rats aggravated ischemia-reperfusion injury and increased infarction area
      through TLR9-p38 MAPK activation. We concluded that mtDNA released into the
      circulation by AMI may has detrimental effect on myocardium through aggravating
      ischemia-reperfusion injury via TLR9-p38 MAPK pathway.

PMID- 28757324
TI  - Silicon containing ibuprofen derivatives with antioxidant and anti-inflammatory
      activities: An in vivo and in silico study.
AB  - There are many chronic diseases related with inflammation. The chronic
      inflammation can produce other problems as cancer. Therefore, it is necessary to
      design drugs with better anti-inflammatory activity than those in the clinic.
      Likewise, these could be used in chronic treatments with minimum adverse effects.
      The amide or ester functionality in combination with the insertion of a silyl
      alkyl moiety is able to improve some drug properties. In this context, the
      evaluation of a group of silicon containing ibuprofen derivatives (SCIDs) as
      antioxidants and anti-inflammatory agents is reported. Antioxidant activity was
      evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH?), 2,2'-Azino-bis(3
      ethylbenzothiazoline-6-sulfonic) acid (ABTS*+) and the Fe(II) chelating ability
      methods. The anti-inflammatory activity was determined by using the carrageenan
      induced rat paw edema. The gastrotoxic profile of the SCIDs that displayed
      significant anti-inflammatory activity was determined by the indomethacin induced
      ulceration method. The SCIDs performed better than ibuprofen as chelating agents
      for Fe(II) and as scavengers for the free radicals DPPH* and ABTS*+. On the anti
      inflammatory test, compound 4a inhibited the edema up to 87%, while 4d &10b
      achieved significant inflammation inhibition at a lower effective dose 50 (ED50)
      than ibuprofen's. None of the SCIDs endowed with anti-inflammatory activity,
      showed significant gastrotoxic effects with respect to those displayed by
      ibuprofen. Based on the experimental results and aided by the theoretical docking
      approach, it was possible to rationalize how the SCIDs may bind to cyclooxygenase
      isoforms and helped to explain their reduced gastrotoxicity. The evaluated
      effects were improved in SCIDs with respect to ibuprofen.

PMID- 28757326
TI  - Proteome oxidative carbonylation during oxidative stress-induced premature
      senescence of WI-38 human fibroblasts.
AB  - Accumulation of oxidatively damaged proteins is a hallmark of cellular and
      organismal ageing, and is also a phenotypic feature shared by both replicative
      senescence and stress-induced premature senescence of human fibroblasts.
      Moreover, proteins that are building up as oxidized (i.e. the "Oxi-proteome")
      during ageing and age-related diseases represent a restricted set of cellular
      proteins, indicating that certain proteins are more prone to oxidative
      carbonylation and subsequent intracellular accumulation. The occurrence of
      specific carbonylated proteins upon oxidative stress induced premature senescence
      of WI-38 human fibroblasts and their follow-up identification have been addressed
      in this study. Indeed, it was expected that the identification of these proteins
      would give insights into the mechanisms by which oxidatively damaged proteins
      could affect cellular function. Among these proteins, some are belonging to the
      cytoskeleton while others are mainly involved in protein quality control and/or
      biosynthesis as well as in redox and energy metabolism, the impairment of which
      has been previously associated with cellular ageing. Interestingly, the majority
      of these carbonylated proteins were found to belong to functional interaction
      networks pointing to signalling pathways that have been implicated in the
      oxidative stress response and subsequent premature senescence.

PMID- 28757328
TI  - Interferon-gamma causes mood abnormalities by altering cannabinoid CB1 receptor
      function in the mouse striatum.
AB  - Interferon-gamma (IFN-gamma) has been implicated in the pathogenesis of multiple
      sclerosis (MS) and in its animal model, experimental autoimmune encephalomyelitis
      (EAE). The type-1 cannabinoid receptors (CB1Rs) are heavily involved in MS
      pathophysiology, and a growing body of evidence suggests that mood disturbances
      reflect specific effects of proinflammatory cytokines on neuronal activity. Here,
      we investigated whether IFN-gamma could exert a role in the anxiety- and
      depressive-like behavior observed in mice with EAE, and in the modulation of
      CB1Rs. Anxiety and depression in fact are often diagnosed in MS, and have already
      been shown to depend on cannabinoid system. We performed biochemical, behavioral
      and electrophysiological experiments to assess the role of IFN-gamma on mood
      control and on synaptic transmission in mice. Intracerebroventricular delivery of
      IFN-gamma caused a depressive- and anxiety-like behavior in mice, associated with
      the selective dysfunction of CB1Rs controlling GABA transmission in the striatum.
      EAE induction was associated with increased striatal expression of IFN-gamma, and
      with CB1R transmission deficits, which were rescued by pharmacological blockade
      of IFN-gamma. IFN-gamma was unable to replicate the effects of EAE on excitatory
      and inhibitory transmission in the striatum, but mimicked the effects of EAE on
      CB1R function in this brain area. Overall these results indicate that IFN-gamma
      exerts a relevant control on mood, through the modulation of CB1R function. A
      better understanding of the biological pathways underling the psychological
      disorders during neuroinflammatory conditions is crucial for developing effective
      therapeutic strategies.

PMID- 28757327
TI  - Differential electrophysiological and morphological alterations of
      thalamostriatal and corticostriatal projections in the R6/2 mouse model of
      Huntington's disease.
AB  - Huntington's disease (HD) is a fatal genetic disorder characterized by cell death
      of medium-sized spiny neurons (MSNs) in the striatum, traditionally attributed to
      excessive glutamate inputs and/or receptor sensitivity. While changes in
      corticostriatal projections have typically been studied in mouse models of HD,
      morphological and functional alterations in thalamostriatal projections have
      received less attention. In this study, an adeno-associated virus expressing
      channelrhodopsin-2 under the calcium/calmodulin-dependent protein kinase IIalpha
      promoter was injected into the sensorimotor cortex or the thalamic centromedian
      parafascicular nuclear complex in the R6/2 mouse model of HD, to permit selective
      activation of corticostriatal or thalamostriatal projections, respectively. In
      symptomatic R6/2 mice, peak amplitudes and areas of corticostriatal glutamate
      AMPA and NMDA receptor-mediated responses were reduced. In contrast, although
      peak amplitudes of AMPA and NMDA receptor-mediated thalamostriatal responses also
      were reduced, the areas remained unchanged due to an increase in response decay
      times. Blockade of glutamate reuptake further increased response areas and slowed
      rise and decay times of NMDA responses. These effects appeared more pronounced at
      thalamostriatal synapses of R6/2 mice, suggesting increased activation of
      extrasynaptic NMDA receptors. In addition, the probability of glutamate release
      was higher at thalamostriatal than corticostriatal synapses, particularly in R6/2
      mice. Morphological studies indicated that the density of all excitatory synaptic
      contacts onto MSNs was reduced, which matches the basic electrophysiological
      findings of reduced amplitudes. There was a consistent reduction in the area of
      spines but little change in presynaptic terminal size, indicating that the
      postsynaptic spine may be more significantly affected than presynaptic terminals.
      These results highlight the significant and differential contribution of the
      thalamostriatal projection to glutamate excitotoxicity in HD.

PMID- 28757329
TI  - Infections following surgical patent ductus arteriosus ligation in very-low
      birthweight neonates.
AB  - BACKGROUND: Very-low-birthweight (VLBW) neonates (<1500g) comprise approximately
      1% of liveborn infants in Poland. Patent ductus arteriosus (PDA) is a common
      complication of prematurity. This study aimed to determine how many VLBW neonates
      treated in the participating units needed surgical correction of PDA, and to
      evaluate the incidence of various types of postoperative infections and their
      microbiology. METHODS: Observational study in five neonatology departments by the
      Polish Neonatology Surveillance Network, involving 2039 VLBW newborns of whom 103
      (5.1%) required surgical PDA ligation. Continuous infection surveillance was
      conducted between 2009 and 2013; infections were defined based on Gastmeier's
      criteria. RESULTS: PDA surgery was required significantly more frequently in
      infants from multiple pregnancies, and where labour was complicated by
      amnionitis. Surgical PDA correction was performed, on average, at 19 days of
      life. The incidence of infection was 48.5% (N = 50), and the most common
      infections were bloodstream infection (26.2%) and pneumonia (22.3%). A
      correlation was observed between the day on which the procedure was performed and
      the time of infection: the earlier the neonate underwent PDA surgery, the earlier
      the infection manifested (P = 0.032). A high CRIB score and chorioamnionitis
      contributed significantly to the presence of infection. CONCLUSION: The later the
      PDA surgery was performed, the later the infection occurred. The incidence of
      infection after correction of PDA among VLBW neonates was comparable with the
      incidence of infection among all hospitalized VLBW neonates.

PMID- 28757330
TI  - Cross-Cultural Adaptation and Validation of the FRAIL Scale in Chinese Community
      Dwelling Older Adults.
AB  - OBJECTIVE: To cross-culturally adapt and test the FRAIL scale in Chinese
      community-dwelling older adults. DESIGN: Cross-sectional study. METHODS: The
      Chinese FRAIL scale was generated by translation and back-translation. An urban
      sample of 1235 Chinese community-dwelling older adults was enrolled to test its
      psychometric properties, including convergent validity, criterion validity, known
      group divergent validity, internal consistency and test-retest reliability.
      RESULTS: The Chinese FRAIL scale achieved semantic, idiomatic, and experiential
      equivalence. The convergent validity was confirmed by statistically significant
      kappa coefficients (0.209-0.401, P < .001) of each item with its corresponding
      alternative measurement, including the 7th item of the Center for Epidemiologic
      Studies-Depression Scale, the Timed Up and Go test, 4-m walking speed,
      polypharmacy, and the Short-Form Mini Nutritional Assessment. Using the Fried
      frailty phenotype as an external criterion, the Chinese FRAIL scale showed
      satisfactory diagnostic accuracy for frailty (area under the curve = 0.91). The
      optimal cut-point for frailty was 2 (sensitivity: 86.96%, specificity: 85.64%).
      The Chinese FRAIL scale had fair agreement with the Fried frailty phenotype
      (kappa = 0.274, P < .001), and classified more participants into frailty (17.2%)
      than the Fried frailty phenotype (3.9%). More frail individuals were recognized
      by the Chinese FRAIL scale among older and female participants than their
      counterparts (P < .001), respectively. It had low internal consistency (Kuder
      Richardson formula 20 = 0.485) and good test-retest reliability within a 7- to 15
      day interval (intraclass correlation coefficient = 0.708). CONCLUSIONS: The
      Chinese FRAIL scale presents acceptable validity and reliability and can apply to
      Chinese community-dwelling older adults.

PMID- 28757331
TI  - Lifestyle Approaches for People With Intellectual Disabilities: A Systematic
      Multiple Case Analysis.
AB  - BACKGROUND: Health care organizations supporting individuals with intellectual
      disabilities (IDs) carry out a range of interventions to support and improve a
      healthy lifestyle. However, it is difficult to implement an active and healthy
      lifestyle into daily support. The presence of numerous intervention components,
      multiple levels of influence, and the explicit use of theory are factors that are
      considered to be essential for implementation in practice. A comprehensive
      written lifestyle policy provides for sustainability of a lifestyle approach. It
      is unknown to what extent these crucial factors for successful implementation are
      taken into consideration by health care organizations supporting this population.
      AIM: To analyze the intervention components, levels of influence, explicit use of
      theory, and conditions for sustainability of currently used lifestyle
      interventions within lifestyle approaches aiming at physical activity and
      nutrition in health care organizations supporting people with ID. METHODS: In
      this descriptive multiple case study of 9 health care organizations, qualitative
      data of the lifestyle approaches with accompanying interventions and their
      components were compiled with a newly developed online inventory form. RESULTS:
      From 9 health care organizations, 59 interventions were included, of which 31%
      aimed to improve physical activity, 10% nutrition, and 59% a combination of both.
      Most (49%) interventions aimed at the educational component and less at daily
      (19%) and generic activities (16%) and the evaluation component (16%). Most
      interventions targeted individuals with ID and the professionals whereas social
      levels were underrepresented. Although 52% of the interventions were structurally
      embedded, only 10 of the 59 interventions were theory-driven. CONCLUSION: Health
      care organizations could improve their lifestyle approaches by using an explicit
      theoretical basis by expanding the current focus of the interventions that
      primarily concentrate on their clients and professionals toward also targeting
      the social and external environment as well as the introduction of a written
      lifestyle policy. This policy should encompass all interventions and should be
      the responsibility of those in the organization working with individuals with ID.
      In conclusion, comprehensive, integrated, and theory-driven approaches at
      multiple levels should be promoted.

PMID- 28757325
TI  - Scar management in burn injuries using drug delivery and molecular signaling:
      Current treatments and future directions.
AB  - In recent decades, there have been tremendous improvements in burn care that have
      allowed patients to survive severe burn injuries that were once fatal. However, a
      major limitation of burn care currently is the development of hypertrophic scars
      in approximately 70% of patients. This significantly decreases the quality of
      life for patients due to the physical and psychosocial symptoms associated with
      scarring. Current approaches to manage scarring include surgical techniques and
      non-surgical methods such as laser therapy, steroid injections, and compression
      therapy. These treatments are limited in their effectiveness and regularly fail
      to manage symptoms. As a result, the development of novel treatments that aim to
      improve outcomes and quality of life is imperative. Drug delivery that targets
      the molecular cascades of wound healing to attenuate or prevent hypertrophic
      scarring is a promising approach that has therapeutic potential. In this review,
      we discuss current treatments for scar management after burn injury, and how drug
      delivery targeting molecular signaling can lead to new therapeutic strategies.

PMID- 28757332
TI  - Prediction of the Incidence of Falls and Deaths Among Elderly Nursing Home
      Residents: The SENIOR Study.
AB  - OBJECTIVE: The objective of this study was to evaluate, among nursing home
      residents, the extent to which the various operational definitions of frailty
      predict mortality and falls at 1 year. METHODS: We studied 662 participants from
      the Sample of Elderly Nursing home Individuals: An Observational Research
      (SENIOR) cohort aged 83.2 +/- 8.99 years, including 484 (72.5%) women and living
      in nursing homes. Among this cohort, 584 and 565 participants, respectively, were
      monitored over 12 months for mortality assessment and for occurrence of falls
      (ie, by mean of their medical records). Each patient was subjected to a clinical
      examination at baseline, during which many original clinical characteristics were
      collected. Stepwise regression analyses were carried out to predict mortality and
      falls. RESULTS: Among the participants included in the study, 93 (15.9%) died and
      211 (37.3%) experienced a fall during the 1-year of follow-up. After adjustment,
      none of the definitions of frailty assessed predicted the 1-year occurrence of
      negative health outcomes. When comparing the clinical characteristics of deceased
      participants and those still alive, being a man (OR = 1.89; 95% CI: 1.19-3.01; P
      = .002) and being diagnosed with sarcopenia (OR = 1.7; 95% CI: 1.1-2.92; P = .03)
      were independent factors associated with 1-year mortality. Other independent
      factors that were significantly associated with the 1-year occurrence of falls
      were the results obtained with the Tinetti test (OR = 0.93; 95% CI: 0.87-0.98; P
      = .04), with the grip strength test (OR = 0.95; 95% CI: 0.90-0.98, P = .03), and
      with the isometric strength test of elbow extensors (OR = 0.93; 95%CI: 0.87-0.97;
      P = .04). CONCLUSIONS: Within the operational definitions of frailty assessed,
      none is sufficiently sensitive to predict the occurrence of falls and deaths at 1
      year among nursing home residents. Globally, the frequency of undesirable health
      outcomes seems to be higher among participants with lower muscle strength and
      mobility. Medical strategy or adapted physical activity, with the aim of
      improving specific isometric muscle strength and mobility could potentially, but
      significantly, reduce the occurrence of falls and even deaths.

PMID- 28757333
TI  - Heterogeneity of Different Tools for Detecting the Prevalence of Frailty in
      Nursing Homes: Feasibility and Meaning of Different Approaches.
AB  - BACKGROUND AND OBJECTIVE: The identification of frail individuals has been
      recognized as a priority for the effective implementation of healthy aging
      strategies. Only a limited number of studies have examined frailty in nursing
      homes, and there is a big heterogeneity in the methods used. The primary
      objective of this study was to determine the prevalence and feasibility of
      different frailty screening tools in nursing homes as well as its relationship
      with multimorbidity and disability. DESIGN, SETTING, AND PARTICIPANTS: Cross
      sectional analysis from a concurrent cohort study, which included 110
      participants aged over 65 years and with different degrees of disability at 2
      nursing homes. MEASUREMENTS: The study used 4 different frailty scales: The Fried
      frailty criteria, the imputed Fried frailty criteria, the Rockwood clinical
      frailty scale, and the frailty in nursing home scale, and we analyzed their
      relationship with disability and multimorbidity. RESULTS: The mean age of the
      study population was 86.3 years (standard deviation 7.3), and 71.8% were female.
      Most residents had a high percentage of cognitive and functional impairment,
      multimorbidity, and risk of malnutrition. The following prevalence rates for
      frailty were determined: 71.8% (62.8, 79.4), 42.7% (33.9, 52.1), and 36.4% (23.8,
      51.1) as per according to the Rockwood clinical frailty scale, frailty in nursing
      home scale, and Fried index (95% confidence interval), respectively. In the case
      of the Fried index, the prevalence of frailty is based on the percentage of
      patients meeting the criteria, which is 40% due to the large number of missing
      values. After the imputation of variables with the multivariate imputation by
      chained equation software, the prevalence of frailty increased to 66.4% (57.1,
      74.5). We observed different statistically significant associations between the
      frailty scales and the clinical and demographic variables, and also with
      disability and multimorbidity. CONCLUSIONS: Most residents of nursing homes are
      likely to be frail, but there is no single operational definition of frailty.
      Although all measures of frailty had similar associations with the clinical
      variables of the study, there are important conceptual differences that must be
      considered in addressing the relationships between frailty, disability, and
      multimorbidity. Further research is required, and homogeneous frailty criteria
      must be used so that studies and interventions can be compared.

PMID- 28757334
TI  - Successfully Reducing Hospitalizations of Nursing Home Residents: Results of the
      Missouri Quality Initiative.
AB  - PURPOSE: The goals of the Missouri Quality Initiative (MOQI) for long-stay
      nursing home residents were to reduce the frequency of avoidable hospital
      admissions and readmissions, improve resident health outcomes, improve the
      process of transitioning between inpatient hospitals and nursing facilities, and
      reduce overall healthcare spending without restricting access to care or choice
      of providers. The MOQI was one of 7 program sites in the United States, with
      specific interventions unique to each site tested for the Centers for Medicaid
      and Medicare Services (CMS) Innovations Center. DESIGN AND METHODS: A
      prospective, single group intervention design, the MOQI included an advanced
      practice registered nurse (APRN) embedded full-time within each nursing home (NH)
      to influence resident care outcomes. Data were collected continuously for more
      than 3 years from an average of 1750 long-stay Medicare, Medicaid, and private
      pay residents living each day in 16 participating nursing homes in urban, metro,
      and rural communities within 80 miles of a major Midwestern city in Missouri.
      Performance feedback reports were provided to each facility summarizing their all
      cause hospitalizations and potentially avoidable hospitalizations as well as a
      support team of social work, health information technology, and INTERACT/Quality
      Improvement Coaches. RESULTS: The MOQI achieved a 30% reduction in all-cause
      hospitalizations and statistically significant reductions in 4 single quarters of
      the 2.75 years of full implementation of the intervention for long-stay nursing
      home residents. IMPLICATIONS: As the population of older people explodes in
      upcoming decades, it is critical to find good solutions to deal with increasing
      costs of health care. APRNs, working with multidisciplinary support teams, are a
      good solution to improving care and reducing costs if all nursing home residents
      have access to APRNs nationwide.

PMID- 28757335
TI  - Imaging in cutis laxa syndrome caused by a dominant negative ALDH18A1 mutation,
      with hypotheses for intracranial vascular tortuosity and wide perivascular
      spaces.
AB  - The autosomal dominant progeroid form of cutis laxa is a recently identified
      multiple congenital anomaly disorder characterized by thin, wrinkled skin, a
      progeroid appearance, intra-uterine growth retardation, postnatal growth
      restriction, psychomotor developmental delay, microcephaly, cataract, hypotonia
      and contractures. De novo heterozygous mutations in ALDH18A1 have been described
      in this condition. We present neuroimaging abnormalities in three patients. One
      patient had intracranial arterial and venous tortuosity, widened ventricular and
      extra-axial cerebrospinal fluid (CSF) spaces, wide perivascular spaces and
      increased T2 signal intensity in the cerebral white matter over time. The second
      patient had vascular tortuosity. The third patient had prominent ventricular and
      extra-axial cerebrospinal fluid (CSF) spaces on CT. We propose an embryological
      mechanism for the development of intracranial vascular tortuosity and discuss the
      anatomical basis of wide perivascular spaces in relation to this syndrome.
      Although we do not know the clinical implications of these cerebral vascular
      anomalies, we suggest inclusion of neuroimaging in the baseline evaluation of
      these patients.

PMID- 28757336
TI  - Double Trouble: A Case Series on Concomitant Genetic Aberrations in NSCLC.
AB  - Several oncogenic drivers have been identified in non-small cell lung cancer.
      Targeted therapies for these aberrations have already been successfully developed
      and implemented in clinical practice. Owing to improved sensitivity in genetic
      testing, more and more tumors with multiple driver mutations are identified,
      resulting in dilemmas for treating physicians whether and which targeted therapy
      to use. In this case series, we provide an overview of patients with intrinsic
      double mutations in oncogenic drivers and their reported response to targeted
      therapies, with a focus on epidermal growth factor receptor, anaplastic lymphoma
      kinase, cMET, and Kirsten rat sarcoma viral oncogene. We also include an
      unpublished case report on a patient with an epidermal growth factor receptor
      L858R and cMET exon 14 skipping.

PMID- 28757337
TI  - Differentiating physicochemical properties between NDRIs and sNRIs clinically
      important for the treatment of ADHD.
AB  - BACKGROUND: Drugs available for treating attention-deficit hyperactivity disorder
      (ADHD) are mainly selective norepinephrine (sNRIs) and dual norepinephrine
      dopamine (NDRIs) reuptake inhibitors. The major problem of sNRIs lines in their
      delayed onset of action and partial- or non-responses, which makes NDRIs
      distinguished in drug efficacy. Understanding of the differential binding modes
      of these 2 types of drugs to their corresponding targets can give great insights
      into the discovery of privileged drug-like scaffolds with improved efficacy. So
      far, no such study has been carried out. METHODS: A combinatorial computational
      strategy, integrating homology modeling, molecular docking, molecular dynamics
      (MD) and binding free energy calculation, was employed to analyze the binding
      modes of 8 clinically important ADHD drugs in their targets. RESULTS: Binding
      modes of 2 types of ADHD drugs (sNRIs and NDRIs) in their targets was identified
      for the first time by MD simulation, and 15 hot spot residues were discovered as
      crucial for NDRIs' binding in hNET and hDAT. Comparing to sNRIs, a clear
      reduction in the hydrophobic property of NDRIs' one functional group was
      observed, and the depth of drugs' aromatic ring stretched into the pocket of both
      targets was further identified as key contributors to drugs' selectivity.
      CONCLUSIONS: The hydrophobic property of NDRI ADHD drugs' one functional group
      contributes to their selectivity when bind hNET and hDAT. GENERAL SIGNIFICANCE:
      These results provide insights into NDRI ADHD drugs' binding mechanisms, which
      could be utilized as structural blueprints for assessing and discovering more
      efficacious drugs for ADHD therapy.

PMID- 28757339
TI  - Human leukocyte antigen A, B and Hepatitis B infection outcome: A meta-analysis.
AB  - AIM: To evaluate the association between HLA A, B with chronic Hepatitis B by
      comprehensive meta-analysis. METHODS: We searched PubMed and Cochrane databases,
      identified relevant studies, evaluated these for quality by New Castle Ottawa
      scale (NOS) and further analyzed the qualified data sets. Heterogeneity analyses
      were performed by Cochrane's Q test and I2 tests. Pooled Odds ratio (OR) & 95%
      Confidence Interval (CI) were obtained by fixed effects, using Mantel-Haenszel's
      method for homogenous studies, and by using DerSimonian and Laird's method for
      heterogenous studies. Publication bias was determined by the Beggs test and
      Eggers test and all tests were two tailed to evaluate their significance.
      RESULTS: The meta-analyses on 1652 healthy controls and 659 Chronic Hepatitis B
      (CHB) patients from 8 studies from various continents revealed a HLA B*07 (p
      value of Odds ratio (pOR)=0.004; OR Fixed effects=0.480 with 95%CI 0.290-0.794)
      and B*58 (pOR=0.029; OR Fixed Effects=0.020 with 95%CI 0.381-0.949) associated
      protection for CHB. The identified HLA B*35 associated risk (pOR 0.009; OR Fixed
      effect 1.445; 95% confidence interval 1.094-1.907) however did not stand the test
      of random effect model. CONCLUSION: While HLA B*07 and B*58 are protective
      against CHB. The HLA B*35 associated marginal risk need to be further validated
      in well-designed global study on larger cohorts, considering the population,
      ethnic, epidemiological and HLA diversity at the sequence level: these may throw
      further light to utilize these markers in predictive medicine.

PMID- 28757340
TI  - Retro-odontoid pseudo-tumor due to calcium pyrophosphate crystal deposits with
      spinal cord compression and histopathological confirmation.

PMID- 28757341
TI  - Motivators for and barriers to physical activity in people with knee
      osteoarthritis: A qualitative study.
AB  - OBJECTIVES: We aimed to explore the motivators for and barriers to regular
      physical activity in people with knee osteoarthritis. METHODS: We performed a
      cross-sectional, monocentric qualitative study based on 20 semi-structured
      individual interviews and two focus groups. People with knee osteoarthritis
      according to American College of Rheumatology criteria were recruited from spa
      therapy resorts (Royat, France). Data were collected by interviews, which were
      then transcribed and coded. The analysis was performed according to the
      researcher triangulation method. RESULTS: Among the 27 participants (17 women),
      the mean age was 67years (SD 7.8) and mean body mass index 29.2kg/m2 (SD 8.2).
      The motivators for physical activity were physical (well-being, decreased pain,
      self-perception), personal (lifestyle, psychological well-being), societal
      (relationships, others' views), and environmental (living). The motivators
      differed by gender, with the concept of performance predominant for men and
      others' views for women. The barriers were psychological (fear of pain, lack of
      motivation) and physical (knee pain, asthenia) and were also potentially related
      to life events (depression, hospitalization). CONCLUSIONS: The study population
      had an overall positive idea of the value of physical activity for knee
      osteoarthritis. The participants expressed beliefs and knowledge generally in
      line with current recommendations. Compliance with these recommendations remains
      moderate. An educational support for progressive adapted physical activity and
      identification of barriers and motivators could help improve adherence.

PMID- 28757338
TI  - Soluble epoxide hydrolase in podocytes is a significant contributor to renal
      function under hyperglycemia.
AB  - BACKGROUND: Diabetic nephropathy (DN) is the leading cause of renal failure, and
      podocyte dysfunction contributes to the pathogenesis of DN. Soluble epoxide
      hydrolase (sEH, encoded by Ephx2) is a conserved cytosolic enzyme whose
      inhibition has beneficial effects on renal function. The aim of this study is to
      investigate the contribution of sEH in podocytes to hyperglycemia-induced renal
      injury. MATERIALS AND METHODS: Mice with podocyte-specific sEH disruption (pod
      sEHKO) were generated, and alterations in kidney function were determined under
      normoglycemia, and high-fat diet (HFD)- and streptozotocin (STZ)-induced
      hyperglycemia. RESULTS: sEH protein expression increased in murine kidneys under
      HFD- and STZ-induced hyperglycemia. sEH deficiency in podocytes preserved renal
      function and glucose control and mitigated hyperglycemia-induced renal injury.
      Also, podocyte sEH deficiency was associated with attenuated hyperglycemia
      induced renal endoplasmic reticulum (ER) stress, inflammation and fibrosis, and
      enhanced autophagy. Moreover, these effects were recapitulated in immortalized
      murine podocytes treated with a selective sEH pharmacological inhibitor.
      Furthermore, pharmacological-induced elevation of ER stress or attenuation of
      autophagy in immortalized podocytes mitigated the protective effects of sEH
      inhibition. CONCLUSIONS: These findings establish sEH in podocytes as a
      significant contributor to renal function under hyperglycemia. GENERAL
      SIGNIFICANCE: These data suggest that sEH is a potential therapeutic target for
      podocytopathies.

PMID- 28757342
TI  - Rheumatoid arthritis treated with tocilizumab in two patients with complicated
      chronic liver disease with portal hypertension.
AB  - Erosive, active rheumatoid arthritis inpatients with portal hypertension
      combining esophageal varices and ascites complicating chronic liver disease poses
      serious management problems. Current literature does not provide any valid
      therapeutic management. We report the case of a woman and a man aged 52 and 66
      years respectively having this combination of pathologies. Infusions of 4mg/kg of
      tocilizumab as monotherapy have produced a weaning from corticosteroids, both
      clinical and structural remission, with particular liver safety satisfactory at
      10 and 18 months.

PMID- 28757343
TI  - Flexor tenosynovitis of the wrist including rice bodies.

PMID- 28757344
TI  - Clinical predictors of magnetic resonance imaging-detected sacroiliitis in
      children with enthesitis related arthritis.
AB  - OBJECTIVES: To determine the predictors of sacroiliitis detected by magnetic
      resonance imaging (MRI) in children with enthesitis-related arthritis. METHODS:
      In this retrospective, longitudinal study, we retrieved clinical and laboratory
      data from the charts of patients with confirmed enthesitis related arthritis and
      evaluated their association with magnetic sacroiliitis detected at first MRI
      after disease onset. The MRI images of sacroiliac joints were read by 2
      independent radiologists and validated against those from 25 age- and sex-matched
      subjects with known non-rheumatologic conditions. RESULTS: We reviewed the
      clinical records of 20 patients with enthesitis-related arthritis for whom MRI
      images of sacroiliac joints were available. Five had bilateral MRI sacroiliitis,
      3 unilateral sacroiliitis while 12 had no sacroiliitis. All MRI images of
      sacroiliiitis showed bone-marrow oedema but no erosions, sclerosis or sacroiliac
      enthesitis. Personal history of buttock pain or abnormal physical examination of
      sacroiliac joints predicted MRI sacroiliitis with a positive predictive value of
      0.75 (95% confidence interval 0.35-0.95). In the absence of these clinical
      elements, MRI sacroiliitis was unlikely to be found (negative predictive value
      0.83; 95% confidence interval 0.50-0.97). CONCLUSION: In children with enthesitis
      related arthritis the presence of buttock pain or of abnormal sacroiliac joint
      examination is a strong predictor of magnetic sacroiliitis.

PMID- 28757345
TI  - Re: "Gulisano M, Domini C, Capelli M, Pellico A, Rizzo R. Importance of
      neuropsychiatric evaluation in children with primary monosymptomatic enuresis." J
      Pediatr Urol 2017;13:36.e1-36.e6.

PMID- 28757347
TI  - A double-masked randomized trial of postoperative local anesthetic for pain
      control in pediatric strabismus surgery.

PMID- 28757346
TI  - Development of an XBP1 agonist, HLJ2, as a potential therapeutic agent for
      ulcerative colitis.
AB  - There is a severe lack of effective treatments for ulcerative colitis (UC), a
      recurrent and intractable inflammatory bowel disease. The identification of valid
      targets and new drugs is an urgent need. In this study, we identified the XBP-1
      agonist HLJ2 as a promising treatment candidate. In an in vivo mouse model of DSS
      induced colitis, HLJ2 decreased weight loss, colon contracture, disease activity
      index (DAI), colon mucosa damage index (CMDI) and histopathological index (HI).
      HLJ2 also decreased myeloperoxidase (MPO) activity and reduced production of the
      inflammatory cytokines TNF-alpha, IL-1beta, and IL-6. HLJ2 improved intestinal
      mucosa damage induced by dextran sodium sulfate (DSS) and increased the
      expression of ZO-1 and claudin-1. Fecal 16s rRNA high-throughput sequencing
      demonstrated a significant improvement in UC intestinal dysbacteriosis in mice
      treated with HLJ2, including increased abundance of probiotics such as
      Lachnospiraceae, Prevotellaceae, and Lactobacillaceae. At the same time there was
      a reduction in the abundance of pathogenic or conditional pathogenic
      microorganisms such as Bacteroidaceae, Porphyromonadaceae, Deferribacteraceae,
      and Pseudomonadaceae in HLJ2-treated mice compared with untreated mice. Our
      results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation, regulates
      the intestinal flora, and protects the intestinal mucosa. It is thus a potential
      therapeutic agent for ulcerative colitis.

PMID- 28757348
TI  - Draft genome sequence of an aminoglycoside-resistant RmtD2-producing Enterobacter
      cloacae subsp. cloacae ST395 in Brazil.
AB  - OBJECTIVES: Enterobacter cloacae has recently emerged as an important agent of
      nosocomial infections owing to the dissemination of extended-spectrum beta
      lactamases and carbapenemases in this species. In this context, a rise in the
      therapeutic use of aminoglycosides was noticed, followed by the accelerated
      development of resistance mechanisms. In this study, we report the draft genome
      sequence of a multidrug-resistant E. cloacae subsp. cloacae strain (Ec2) isolated
      from an active surveillance culture of a patient with Chagas disease. METHODS:
      Whole-genome sequencing (WGS) was performed using a Nextera XT DNA library and
      NextSeq platform. RESULTS: WGS analysis revealed the presence of 5527 coding
      genes, 62 RNA-encoding genes and 275 pseudogenes. Strain Ec2 belongs to sequence
      type 395 (ST395) and carries 22 transferable antibiotic resistance genes,
      comprising eight antimicrobial classes, including the rmtD2 gene conferring high
      level aminoglycoside resistance. CONCLUSIONS: This draft genome can be used in
      comparative genomic analyses with different E. cloacae strains. In addition, it
      could help at elucidating epidemiological aspects regarding the dissemination of
      clinically relevant resistance genes.

PMID- 28757349
TI  - Improved calculations of electron capture transitions for decay data and
      radionuclide metrology.
AB  - Electron capture properties are crucial to establish the decay schemes of
      numerous radionuclides. The present modelling aims at improving the theoretical
      estimates of these decays, which are needed when no measurement is available.
      Allowed and forbidden unique transitions are calculated on the basis of precise
      relativistic wave functions of the atomic electrons, determined in previous work.
      In this context, correcting for atomic effects is of high importance. The two
      common approaches from Bahcall and Vatai to correct for the overlap and exchange
      effects have been extended to every subshell in a unified formulation, with the
      electron occupation precisely taken into account. The shake-up and shake-off
      effects, which create secondary vacancies, and the influence of the hole due to
      the capture process, have been considered. Uncertainties are also estimated.
      Relative capture probabilities and their ratios, including capture-to-positron
      ratios, have been found to be in good agreement with a selection of precise
      measurements. This modelling was then applied to the third forbidden unique
      transition of 40K decay, with an update of the recommended values for the
      branching ratios and the total decay half-life.

PMID- 28757350
TI  - Standardization of 142Pr activity concentration.
AB  - 142Pr (praseodymium-142), a potential radionuclide for brachytherapy, was
      produced after irradiating high purity natural Pr2O3 powder in a research
      reactor. The irradiated powder was then dissolved in acids and diluted for
      measurement. Several radioactivity measurement methods were used in the
      standardization of 142Pr radionuclide. This work reports the results of
      standardization of 142Pr with CIEMAT/NIST efficiency tracing method, gamma
      spectrometry and a calibrated ionization chamber. The activity measured from
      different standardization methods are compatible with each other within the
      uncertainty limits. The CIEMAT/NIST efficiency tracing method gives the lowest
      uncertainty and is a reliable method for the standardization of this
      radionuclide.

PMID- 28757351
TI  - Estimation of effective dose and radiation risk in pediatric barium studies
      procedures.
AB  - The objectives of this study are to assess pediatric radiation exposure in
      certain barium studies and to quantify the organ and effective doses and
      radiation risk resultant from patients' irradiation. A total of 69 pediatric
      barium studies for upper and lower gastrointestinal tract. Patients' radiation
      dose was quantified in terms of Entrance surface air kerma (ESAKs) using exposure
      parameters and DosCal software. Organ and effective doses (E) were extrapolated
      using national Radiological Protection Board software (NRPB-R279). The mean +/-
      (SD) and the range of patient doses per procedure were 3.7 +/- 0.4 (1.0-13.0)mGy,
      7.4 +/- 1.7(5.5-8.0)mGy and 1.4 +/- 0.9 (0.5-3.6)mGy for barium meal, swallow and
      enema, respectively. The mean effective doses were 0.3 +/- 0.03 (0.08-1.1)mSv,
      0.2 +/- 1.6 (0.44-0.7)mSv and 0.3 +/- 0.9 (0.1-0.8)mSv at the same order. The
      radiation dose were higher compared to previous studies. Therefore, pediatrics
      are exposed to avoidable radiation exposure. Certain optimization measures are
      recommended along with establishing national diagnostic reference level (DRL) to
      reduce the radiation risk.

PMID- 28757352
TI  - Concept design of a time-of-flight spectrometer for the measurement of the energy
      of alpha particles.
AB  - The knowledge of the energies of the alpha particles emitted in the radioactive
      decay of a nuclide is a key factor in the construction of its decay scheme.
      Virtually all existing data are based on a few absolute measurements made by
      magnetic spectrometry (MS), to which most other MS measurements are traced. An
      alternative solution would be the use of time-of-flight detectors. This paper
      discusses the main aspects to be considered in the design of such detectors, and
      the performances that could be reasonably expected. Based on the concepts
      discussed here, it is estimated that an energy resolution about 2.5keV may be
      attainable with a good quality source.

PMID- 28757353
TI  - Osmotic and heat stress-dependent regulation of MLK4beta and MLK3 by the CHIP E3
      ligase in ovarian cancer cells.
AB  - Mixed Lineage Kinase 3 (MLK3), a member of the MLK subfamily of protein kinases,
      is a mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) that activates
      MAPK signalling pathways and regulates cellular responses such as proliferation,
      invasion and apoptosis. MLK4beta, another member of the MLK subfamily, is less
      extensively studied, and the regulation of MLK4beta by stress stimuli is not
      known. In this study, the regulation of MLK4beta and MLK3 by osmotic stress,
      thermostress and heat shock protein 90 (Hsp90) inhibition was investigated in
      ovarian cancer cells. MLK3 and MLK4beta protein levels declined under conditions
      of prolonged osmotic stress, heat stress or exposure to the Hsp90 inhibitor
      geldanamycin (GA); and MLK3 protein declined faster than MLK4beta. Similar to
      MLK3, the reduction in MLK4beta protein in cells exposed to heat or osmotic
      stresses occurred via a mechanism that involves the E3 ligase, carboxy-terminus
      of Hsc70-interacting protein (CHIP). Both heat shock protein 70 (Hsp70) and CHIP
      overexpression led to polyubiquitination and a decrease in endogenous MLK4beta
      protein, and MLK4beta was ubiquitinated by CHIP in vitro. In untreated cells and
      cells exposed to osmotic and heat stresses for short time periods, small
      interfering RNA (siRNA) knockdown of MLK4beta elevated the levels of activated
      MLK3, c-Jun N-terminal kinase (JNK) and p38 MAPKs. Furthermore, MLK3 binds to
      MLK4beta, and this association is regulated by osmotic stress. These results
      suggest that in the early response to stressful stimuli, MLK4beta-MLK3 binding is
      important for regulating MLK3 activity and MAPK signalling, and after prolonged
      periods of stress exposure, MLK4beta and MLK3 proteins decline via CHIP-dependent
      degradation. These findings provide insight into how heat and osmotic stresses
      regulate MLK4beta and MLK3, and reveal an important function for MLK4beta in
      modulating MLK3 activity in stress responses.

PMID- 28757354
TI  - Stress-induced hyperacetylation of microtubule enhances mitochondrial fission and
      modulates the phosphorylation of Drp1 at 616Ser.
AB  - Mitochondria dynamics results from fission and fusion events that may be
      unbalanced in favor of mitochondrial fragmentation upon cell stress. During
      oxidative stress, microtubules are hyperacetylated in a mitochondria-dependent
      manner. In this study, we show that under stress conditions, most of the
      mitochondria form foci with microtubule domains that carry Drp1. We also
      demonstrate that stress-induced hyperacetylation of microtubules is required for
      the effective induction of Drp1 phosphorylation at 616Ser, in a kinesin-1- and c
      Jun N-terminal kinase-dependent manner. Furthermore, hyperacetylation of
      microtubules contributes to the recruitment of total Drp1 to mitochondria to
      enhance fission. These results highlight a new way of interaction between
      microtubules and mitochondria dynamics.

PMID- 28757355
TI  - 15-Lipoxygenase-1 re-expression in colorectal cancer alters endothelial cell
      features through enhanced expression of TSP-1 and ICAM-1.
AB  - 15-lipoxygenase-1 (15-LOX-1) oxygenates linoleic acid to 13(S)
      hydroxyoctadecadienoic acid (HODE). The enzyme is widely suppressed in different
      cancers and its re-expression has tumor suppressive effects. 15-LOX-1 has been
      shown to inhibit neoangiogenesis in colorectal cancer (CRC); in the present study
      we confirm this phenomenon and describe the mechanistic basis. We show that re
      expression of 15-LOX-1 in CRC cell lines resulted in decreased transcriptional
      activity of HIF1alpha and reduced the expression and secretion of VEGF in both
      normoxic and hypoxic conditions. Conditioned medium (CM) was obtained from CRC or
      prostate cancer cell lines re-expressing 15-LOX-1 (15-LOX-1CM). 15-LOX-1CM
      treated aortic rings from 6-week old C57BL/6 mice showed significantly less
      vessel sprouting and more organized structure of vascular network. Human
      umbilical vein endothelial cells (HUVECs) incubated with 15-LOX-1CM showed
      reduced motility, enhanced expression of intercellular cell adhesion molecule
      (ICAM-1) and reduced tube formation but no change in proliferation or cell-cycle
      distribution. HUVECs incubated with 13(S)-HODE partially phenocopied the effects
      of 15-LOX-1CM, i.e., showed reduced motility and enhanced expression of ICAM-1,
      but did not reduce tube formation, implying the importance of additional factors.
      Therefore, a Proteome Profiler Angiogenesis Array was carried out, which showed
      that Thrombospondin-1 (TSP-1), a matrix glycoprotein known to strongly inhibit
      neovascularization, was expressed significantly more in HUVECs incubated with 15
      LOX-1CM. TSP-1 blockage in HUVECs reduced the expression of ICAM-1 and enhanced
      cell motility, thereby providing a mechanism for reduced angiogenesis. The anti
      angiogenic effects of 15-LOX-1 through enhanced expressions of ICAM-1 and TSP-1
      are novel findings and should be explored further to develop therapeutic options.

PMID- 28757356
TI  - Flibanserin: From Bench to Bedside.
AB  - INTRODUCTION: The process of approval for flibanserin (trade name Addyi) has been
      associated with controversy since before its approval on August 18, 2015. This
      argument centered on challenges to the validity of the diagnosis of hypoactive
      sexual desire disorder in women and the safety and efficacy of the drug. AIM: To
      explore the process of Food and Drug Administration (FDA) approval for
      flibanserin and delve further into the research, concerns, and various roadblocks
      to its approval. METHODS: A literature review was undertaken using the terms
      flibanserin and hypoactive sexual desire disorder and relevant commentary from
      supporters and critics regarding the medication and difficulties leading up to
      approval. MAIN OUTCOME MEASURES: Review of the process of FDA approval of a
      medication to treat hypoactive sexual desire disorder and research published
      exploring the efficacy and safety of flibanserin. RESULTS: Before flibanserin,
      there were no drugs approved to treat hypoactive sexual desire disorder, which
      has a reported estimated incidence of 10% of women. For studying the
      effectiveness of flibanserin, the FDA required satisfying sexual events as the
      primary end point, although this end point does not measure level of desire or
      the associated distress. The satisfying sexual event measurement was significant
      across all three flibanserin trials in premenopausal women, as was an increase in
      desire according to the Female Sexual Function Index desire domain and a decrease
      in distress as recorded with the Female Sexual Distress Scale-Revised, Item 13.
      Safety concerns centered on the incidence of sedation, syncope, hypotension, and
      the interaction of flibanserin with alcohol and CYP3A4 inhibitors. Additional
      targeted challenge studies were mandated by the FDA. CONCLUSION: The process of
      approval of flibanserin was lengthy. This was due in part to it being the first
      drug in its class and one with no clear guidance on study design from the FDA or
      roadmap for development and approval. Dooley EM, Miller MK, Clayton AH.
      Flibanserin: From Bench to Bedside. Sex Med Rev 2017;5:461-469.

PMID- 28757357
TI  - Erectile Dysfunction Following Pelvic Fracture Urethral Injury.
AB  - INTRODUCTION: Although pelvic fracture urethral injuries (PFUIs) are rare,
      approximately half these patients will report erectile dysfunction (ED) after
      their injuries. The anatomic relations of the cavernosal nerves and arteries to
      the bones of the pelvis and the urethra put these structures at significant risk
      at the time of PFUI. This review examines the epidemiology, evaluation, and
      management of ED in this patient population. AIM: To evaluate the epidemiology,
      pathophysiology, diagnosis, and management of patients with ED after PFUI.
      METHODS: A literature review was performed to identify articles on PubMed
      published before May 2017 addressing PFUI and ED. MAIN OUTCOME MEASURES:
      Incidence, mechanisms, risk factors, evaluation, and management strategies of ED
      after PFUI were analyzed. RESULTS: Patients with pelvic fractures are at risk of
      post-injury ED, whereas those with PFUI appear to be at even higher risk.
      Different potential mechanisms contributing to the pathophysiology of ED in this
      setting have been described in the literature, including damage to the nervous
      supply to the penis, arterial insufficiency, and veno-occlusive dysfunction.
      However, there is a lack of consensus on the predominant etiology. Appropriate
      diagnostic evaluation can help to elucidate the underlying pathophysiology on an
      individual basis and can help guide management. Oral therapies, intracavernosal
      injections, and inflatable penile prostheses have shown great success.
      Furthermore, unlike patients with ED from other causes, select patients with
      isolated arteriogenic ED are potentially eligible for penile revascularization
      procedures. CONCLUSION: Because most patients with pelvic trauma are younger than
      40 years with a significant life expectancy, appropriate diagnosis and management
      of ED after PFUI can greatly improve quality of life and allow resumption of post
      injury sexual function. Identification of the causative pathology can help tailor
      treatment on an individual basis. Johnsen NV, Kaufman MR, Dmochowski RR, Milam
      DF. Erectile Dysfunction Following Pelvic Fracture Urethral Injury. Sex Med Rev
      2018;6;114-123.

PMID- 28757358
TI  - Strontium release from Sr2+-loaded bone cements and dispersion in healthy and
      osteoporotic rat bone.
AB  - Drug functionalization of biomaterials is a modern and popular approach in
      biomaterials research. Amongst others this concept is used for the
      functionalization of bone implants to locally stimulate the bone healing process.
      For example strontium ions (Sr2+) are administered in osteoporosis therapy to
      stimulate bone growth and have recently been integrated into bone cements. Based
      on results of different analytical experiments we developed a two-phase model for
      the transport of therapeutically active Sr2+-ions in bone in combination with
      Korsmeyer-Peppas kinetics for the Sr2+ release from bone cement. Data of cement
      dissolution experiments into water in combination with inductively coupled plasma
      mass spectrometry (ICP-MS) analysis account for dissolution kinetics following
      Noyes-Whitney rule. For dissolution in alpha-MEM cell culture media the process
      is kinetically hindered and can be described by Korsmeyer-Peppas kinetics. Time
      of flight secondary ion mass spectrometry (ToF-SIMS) was used to determine the
      Sr2+ diffusion coefficient in healthy and osteoporotic trabecular rat bone.
      Therefore, bone sections were dipped in aqueous Sr2+-solution by one side and the
      Sr2+-profile was measured by classical SIMS depth profiling. The Sr2+ mobility
      can be described by a simple diffusion model and we obtained diffusion
      coefficients of (2.28+/-2.97)?10-12cm2/s for healthy and of (1.55+/-0.93)?10
      10cm2/s for osteoporotic bone. This finding can be explained by a different bone
      nanostructure, which was observed by focused ion beam scanning electron
      microscopy (FIB-SEM) and transmission electron microscopy (TEM). Finally, the
      time and spatially resolved drug transport was calculated by finite element
      method for the femur of healthy and osteoporotic rats. The obtained results were
      compared to mass images that were obtained from sections of in vivo experiments
      by ToF-SIMS. The simulated data fits quite well to experimental results. The
      successfully applied model for the description of drug dispersion can help to
      reduce the number of animal experiments in the future.

PMID- 28757359
TI  - Identification of cyclic peptides for facilitation of transcellular transport of
      phages across intestinal epithelium in vitro and in vivo.
AB  - Methodology to enhance intestinal absorption of macromolecular drugs is an
      important challenge for developing next-generation biomedicines. So far, various
      cationic cell-penetrating peptides have been reported to facilitate uptake of
      certain bioactive proteins. However, cyclic peptides might be better candidates,
      as they are more metabolically stable than linear peptides. Accordingly, we
      hypothesized that suitable cyclic peptides would promote the absorption of
      macromolecules across intestinal epithelium. To test this idea, we adopted Caco-2
      cell permeability assay as an in vitro human intestinal absorption model, and M13
      phage as a model of macromolecules. Successive screenings of a phage library
      displaying cyclic heptapeptides via a short GGGS linker yielded 3 hits. Among
      them, phage displaying cyclic heptapeptide DNPGNET (DNP-phage) showed the
      greatest permeability across a Caco-2 cell monolayer and mouse intestinal
      epithelium. Interestingly, DNPGNET (DNP) does not contain any basic amino acids.
      Its isoelectric point (pI) was estimated to be 2.72. It did not reduce the
      viability or tight-junction integrity of Caco-2 cells at concentrations up to
      100MUM for 24h. Uptake of either DNP-phage or a fluorescence-labeled DNP
      derivative (AC-DNPGNET-CGGGS modified with 5/6-FAM at the C-terminal; the
      cysteines serve to generate the cyclic peptide via disulfide bond formation, and
      GGGS is the phage linker) by Caco-2 cells was inhibited by low temperature,
      unlabeled AC-DNPGNET-CGGGS and EIPA, a macropinocytosis inhibitor. Thus, DNP
      appears to facilitate transcellular permeability of phages via macropinocytosis,
      but not paracellular diffusion. These findings indicate that DNP is a promising
      candidate as a carrier to promote intestinal absorption of macromolecular drugs.

PMID- 28757361
TI  - Phosphorus protects cardiac tissue by modifying the immune response in rats
      infected by Trypanosoma cruzi.
AB  - AIM: This study evaluates and correlates the number of myocarditis focuses and
      production of cytokines in Rattus norvegicus (Wistar lineage), experimentally
      infected with T. Cruzi and treated with Phosphorus. METHODS: In two blind,
      controlled and randomized trials, 53 45-day-old, male animals were allocated into
      groups Control (n=24): Control group infected and treated with 7% hydroalcoholic
      solution, the preparation vehicle of the test medication; and Phosphorus (n=24 on
      days 0, 5, 10 and 24 after infection): group infected and treated with Phosphorus
      13cH, diluted 10-26 and dynamized (test medication). The animals were inoculated
      intraperitoneally with 5*106 blood trypomastigotes of T. cruzi-Y strain. The
      medication was administered overnight (16 consecutive hours), diluted in water
      (1mL/100mL) in amber water bottles. The animals were treated 2days before and 2,
      4, and 6days after infection. Enumeration of inflammatory foci in cardiac tissue
      (Hematoxylin-Eosin) and dosage of cytokines TNF-alpha and IFN-gamma in the serum
      were performed on days 0, 5, 10 and 24 after infection, using three
      animals/group. Mann-Whitney, Friedman ANOVA, Spearman correlation (p<0.05), and
      Statistica Single User Software version 13.2 were used for data analysis.
      RESULTS: The animals treated with Phosphorus 13cH had high concentration of INF
      gamma on the 5th day of infection with significant decrease on the 10th and 24th
      days (p<0.05), and high concentration of TNF-alpha on the 5th and 10th days of
      infection with decrease on the 24th day (p<0.05). The treatment with Phosphorus
      caused a significant increase of INF-gamma and TNF-alpha on the 5th day of
      infection compared with the Control (p<0.05), with reestablishment on the 24th
      day, as well as in the Control group. The group treated with Phosphorus had 52.5%
      less number of myocarditis focuses in heart than Control group (p<0.05) on the
      10th day of infection. The significant increase in cytokines on the5th day of
      infection in the Phosphorus group is related to a significant decrease in the
      number of inflammatory foci in cardiac tissue on the 10th day of infection in
      this group. DISCUSSION AND CONCLUSION: Treatment with Phosphorus 13cH promotes
      beneficial effects in T. cruzi infection in Wistar rats by modulating the
      secretion of IFN-gamma and TNF-alpha with decreased inflammation in cardiac
      tissue. These results reinforce the importance of considering the use of
      homeopathy for establishing new therapeutic approaches in the management of
      patients with Chagas disease.

PMID- 28757360
TI  - Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain
      Development and Interneuron Migration.
AB  - Organoid techniques provide unique platforms to model brain development and
      neurological disorders. Whereas several methods for recapitulating corticogenesis
      have been described, a system modeling human medial ganglionic eminence (MGE)
      development, a critical ventral brain domain producing cortical interneurons and
      related lineages, has been lacking until recently. Here, we describe the
      generation of MGE and cortex-specific organoids from human pluripotent stem cells
      that recapitulate the development of MGE and cortex domains, respectively.
      Population and single-cell RNA sequencing (RNA-seq) profiling combined with bulk
      assay for transposase-accessible chromatin with high-throughput sequencing (ATAC
      seq) analyses revealed transcriptional and chromatin accessibility dynamics and
      lineage relationships during MGE and cortical organoid development. Furthermore,
      MGE and cortical organoids generated physiologically functional neurons and
      neuronal networks. Finally, fusing region-specific organoids followed by live
      imaging enabled analysis of human interneuron migration and integration.
      Together, our study provides a platform for generating domain-specific brain
      organoids and modeling human interneuron migration and offers deeper insight into
      molecular dynamics during human brain development.

PMID- 28757362
TI  - Dynamized ethyl alcohol improves immune response and behavior in murine infection
      with Trypanosoma cruzi.
AB  - AIM: To evaluate the effects of dynamized ethyl alcohol (Ethylicum)6cH and 30cH
      in mice infected with T. cruzi. METHODS: In a blind, randomized and controlled
      assay, 63 eight-week-old, Swiss, male mice, infected with IP (1400
      trypomastigotes, T. cruzi-Y-strain), were allocated into groups: CNI-non-infected
      (n=12), CI-infected and non-treated (n=17), Et6cH-infected, treated with
      Ethylicum 6cH (dilution 1:1012) (n=17), Et30cH-infected, treated with Ethylicum
      30cH (dilution 1:1060) (n=17). Treatment was administered 48h before and after
      infection, followed by 56h/56h periods, until the 9th day after infection (a.i),
      for 16 h. Survival and mortality were assessed until the 82nd day after infection
      (a.i.). TNF-alpha, IL-6, IL-10, IL-5 and IL-17A cytokines were assessed in serum
      (3-4 animals/group), at time T0 (before infection), T8 and T12 (8th and 12th
      a.i), using the Mouse Cytokine 20-Plex Panel Magnetic Kit (Invitrogen, USA).
      Inflammation was determined in heart sections (eosin-hematoxylin staining) and
      behavior was analyzed with ANY-maze(r) software. The study was approved by the
      Animal Ethics Committee/UEM. Statistica 8.0 and R 3.0.2 software were used for
      statistical analyses. RESULTS: The greater survival observed in the Et6cH group
      was related to decreased inflammation in heart tissue and increased IL-5 at T0
      (p<0.05) and IL-10 at T8 (p<0.05), characterizing the Th2 response. It was also
      related to shorter periods of immobility, observed on day 12 a.i. The higher
      mortality in the Et30cH group was related to increased inflammation in the heart
      and a higher concentration of IL-6 and TNF-alpha cytokines, characterizing the
      Th1 response. CONCLUSION: The results demonstrate the beneficial effect of
      Ethylicum 6cH in acute murine infection by T. cruzi.

PMID- 28757363
TI  - Poly (I:C) alleviates obesity related pro-inflammatory status and promotes
      glucose homeostasis.
AB  - Obesity associated insulin resistance (IR) is implicated in chronic inflammation
      that mediated by the immune system. Imbalance between anti-inflammatory and pro
      inflammatory response contributes to the origins and drivers of IR. However,
      cells of innate and adaptive immune system participate in the pathogenesis of IR,
      while glucose homeostasis related immune tolerance could be compromised high fat
      diet (HFD) reduced metabolic disorder. Although previous studies have
      demonstrated that anti-inflammatory therapy has a protective role in alleviating
      the pro-inflammatory status in HFD induced IR, the precise mechanism is still
      unclear. Ploy (I:C) is a synthetic double-stranded RNA that activates innate
      and/or adaptive immune response via retinoic acid-inducible gene-I (RIG-I), toll
      like receptor 3 (TLR3) and melanoma differentiation-associated protein 5 (MDA5).
      In the present study, we initially perform a novel research on the relationship
      between Poly (I:C) preconditioning and improved glucose metabolism in obesity
      related IR. Interestingly, Poly (I:C) treatment has alleviated the pro
      inflammatory status and promoted glucose homeostasis during a HFD feeding.
      Improved insulin sensitivity is consistent with enhanced immune tolerance, which
      accompanied with increased Foxp3+ regulatory T cells (Tregs). Of note, Tregs have
      a pivotal role in orchestrating the self-balance between autoimmunity and
      inflammation reaction. Thus, our findings reveal that Ploy (I:C) preconditioning
      prevents HFD induced glucose intolerance, which may be recognized as vaccination
      by the host. Overall, selectively targeting precise immune regulators may lead to
      new classes of potentially meaningful therapies for IR in the clinical trials.

PMID- 28757364
TI  - Ehlers Danlos syndrome, kyphoscoliotic type due to Lysyl Hydroxylase 1 deficiency
      in two children without congenital or early onset kyphoscoliosis.
AB  - We report two children with Ehlers Danlos, kyphoscoliotic type confirmed by Lysyl
      Hydroxylase 1 deficiency due to bi-allelic PLOD1 mutations (kEDS-PLOD1) who were
      initially thought to have either a diagnosis of classical EDS (cEDS) or a
      neuromuscular disorder due to absence of (congenital) scoliosis. As the two
      patients reported here illustrate, patients with kEDS-PLOD1 do not always have a
      kyphoscoliosis present at birth or in the first year of life, neither do they
      necessarily develop kyphoscoliosis later in infancy. Using the past criteria for
      kEDS there was considerable overlap with the clinical diagnostic criteria for EDS
      classical type. In the patients reported here without (kypho) scoliosis this has
      delayed the diagnosis, which is unfortunate as the diagnosis of kEDS-PLOD1
      results in a different recurrence risk and has management consequences.
      Interestingly, the new criteria for kEDS would not have prevented this diagnostic
      delay as congenital or early onset kyphoscoliosis (progressive or non
      progressive) is deemed obligatory for the diagnosis of kEDS. Being aware of the
      limitations of clinical diagnostic criteria, we recommend that (i) in patients
      without a positive family history nor identified COL5A1/2 mutations, lysyl
      hydroxylase deficiency or biallelic PLOD1 mutations should be excluded before the
      diagnosis classical EDS can be made and (ii) PLOD1 and COL5A1/2 should be
      included in the same Next Generation Sequencing (NGS) gene panel.

PMID- 28757365
TI  - Assessing chemoreflexes and oxygenation in the context of acute hypoxia:
      Implications for field studies.
AB  - Carotid chemoreceptors detect changes in PO2 and elicit a peripheral respiratory
      chemoreflex (PCR). The PCR can be tested through a transient hypoxic ventilatory
      response test (TT-HVR), which may not be safe nor feasible at altitude. We
      characterized a transient hyperoxic ventilatory withdrawal test in the setting of
      steady-state normobaric hypoxia (13.5-14% FIO2) and compared it to a TT-HVR and a
      steady-state poikilocapnic hypoxia test, within-individuals. No PCR test
      magnitude was correlated with any other test, nor was any test magnitude
      correlated with oxygenation while in steady-state hypoxia. Due to the
      heterogeneity between the different PCR test procedures and magnitudes, and the
      confounding effects of alterations in CO2 acting on both central and peripheral
      chemoreceptors, we developed a novel method to assess prevailing steady-state
      chemoreflex drive in the context of hypoxia. Quantifying peak hypoxic/hyperoxic
      responses at low altitude may have minimal utility in predicting oxygenation
      during ascent to altitude, and here we advance a novel index of chemoreflex
      drive.

PMID- 28757366
TI  - Ibuprofen does not reverse ventilatory acclimatization to chronic hypoxia.
AB  - Ventilatory acclimatization to hypoxia involves an increase in the acute hypoxic
      ventilatory response that is blocked by non-steroidal anti-inflammatory drugs
      administered during sustained hypoxia. We tested the hypothesis that inflammatory
      signals are necessary to sustain ventilatory acclimatization to hypoxia once it
      is established. Adult, rats were acclimatized to normoxia or chronic hypoxia (CH,
      [Formula: see text] =70Torr) for 11-12days and treated with ibuprofen or saline
      for the last 2days of hypoxia. Ventilation, metabolic rate, and arterial blood
      gas responses to O2 and CO2 were not affected by ibuprofen after acclimatization
      had been established. Immunohistochemistry and image analysis showed acute (1h)
      hypoxia activated microglia in a medullary respiratory center (nucleus tractus
      solitarius, NTS) and this was blocked by ibuprofen administered from the
      beginning of hypoxic exposure. Microglia returned to the control state after
      7days of CH and were not affected by ibuprofen administered for 2 more days of
      CH. In contrast, NTS astrocytes were activated by CH but not acute hypoxia and
      activation was not reversed by administering ibuprofen for the last 2days of CH.
      Hence, ibuprofen cannot reverse ventilatory acclimatization or astrocyte
      activation after they have been established by sustained hypoxia. The results are
      consistent with a model for microglia activation or other ibuprofen-sensitive
      processes being necessary for the induction but not maintenance of ventilatory
      acclimatization to hypoxia.

PMID- 28757367
TI  - Hypereosinophilic Syndrome Subtype Predicts Responsiveness to Glucocorticoids.
AB  - BACKGROUND: Glucocorticoids (GCs) are considered first-line treatment for
      platelet-derived growth factor alpha (PDGFRA)-negative hypereosinophilic
      syndromes (HESs). Despite this, little is known about clinical predictors of GC
      responsiveness in HES. OBJECTIVE: Knowledge of clinical and laboratory predictors
      of GC response before initiation of GC could lead to more rational selection of
      subjects with HES for whom earlier institution of second-line and alternative
      therapies would be appropriate. METHODS: Response to GC, as defined by the
      reduction of the absolute eosinophil count to below 1000/mm3 and control of
      symptoms, was assessed by a retrospective chart review of subjects with PDGFRA
      negative HES evaluated on an institutional review board-approved protocol.
      Demographic, clinical, and laboratory parameters obtained before institution of
      GC, as well as final diagnosis, were evaluated to determine predictors of GC
      response. Proportional odds models were used for univariate and multivariate
      assessment of predictors with permutation adjusted P values to correct for
      multiple comparisons. RESULTS: A total of 164 subjects with PDGFRA-negative HES
      were categorized according to GC response. Of them, 39% of the subjects responded
      to low dose (<=10 mg) prednisone, 9% did not respond to GC, and the remainder
      (52%) had variable responses to GC. The HES subtype diagnosis was the best
      predictor of response to GC with myeloid forms and lymphocytic variants of HES
      being the least responsive to GC. CONCLUSIONS: In a large cohort of well
      characterized subjects with HES, the odds of response to GC was predicted by HES
      subtype. Using this model, clinicians may more readily proceed to second-line
      agents in subjects with confirmed lymphocytic or myeloid forms of HES.

PMID- 28757368
TI  - Are dispensing patterns for epinephrine autoinjectors age-appropriate in
      children?

PMID- 28757369
TI  - Rhinosporidiosis.

PMID- 28757371
TI  - Dystonia as an unusual presentation of systemic mastocytosis: Possible link
      between histamine release and movement disorders.

PMID- 28757370
TI  - Distinct Asthma Phenotypes Among Older Adults with Asthma.
AB  - BACKGROUND: Older adults have high rates of asthma morbidity and mortality.
      Asthma is now recognized as a heterogeneous disease, yet the distinct phenotypes
      among older adults are unknown. OBJECTIVE: The objective of this study was to
      identify asthma phenotypes in a diverse population of elderly patients with
      asthma. METHODS: Using cluster analysis, 180 older adults with persistent asthma
      were analyzed. Subjects completed detailed questionnaires, skin prick testing,
      and spirometry with reversibility. Twenty-four core variables were analyzed.
      RESULTS: Four groups were identified. Subjects in cluster 1 (n = 69) typically
      had asthma diagnosed after the age of 40 and the shortest duration of asthma.
      Cluster 2 (n = 40) had the mildest asthma defined by spirometry, Asthma Control
      test (ACT), and Asthma Quality of Life Questionnaire (AQLQ). They also had the
      lowest body mass index (BMI), lowest depression score, and least number of
      comorbidities. Cluster 3 (n = 46) had the longest duration of asthma (56 years)
      and the highest atopic skin test sensitization (74%). Cluster 4 (n = 25) had the
      most severe asthma, with extremely low FEV1% predicted (37.8%), lowest ACT, and
      lowest AQLQ scores. They were more likely to be black and had the highest
      comorbidities. Using BMI, posttreatment FEV1% predicted, and duration of asthma,
      95.6% of subjects were able to be correctly classified. CONCLUSIONS: In older
      adults with asthma, distinct phenotypes vary on key features that are more
      pronounced among the elderly, including comorbidities, fixed airway obstruction,
      and duration of asthma >=40 years. Further work is required to determine the
      clinical and therapeutic implications for different asthma phenotypes in older
      adults.

PMID- 28757372
TI  - Magnetic bead based assays for complement component C5.
AB  - Two novel magnetic agarose bead based assays have been developed to measure
      complement component C5 interaction with C3b and the Factor I Modules (FIMs) of
      C7. One innovation was to couple C3b onto the magnetic agarose bead using the
      alternative pathway C3 convertase, which resulted in a linkage of the ligand by a
      covalent ester bond. A second innovation was to employ nickel ion charged N,N,N'
      tris(carboxymethyl)ethylene-diamine-magnetic agarose to capture recombinantly
      prepared C7 FIMs that were expressed with an oligo-histidine linker followed by
      an acidic domain that provided a spacer enabling the C7 modules exposure to C5.
      Detection was brought about by peroxidase coupled to C5. Both assays exhibited
      adequate statistics suitable for screening. As examples of the utility of these
      new methods, we chose to examine influence of natural products on C5 interaction.
      Fucoidan and beta-glucans were observed to inhibit C3b-C5 interaction, and
      dextran sulfate was similarly active; however, rosmarinic acid had no measurable
      effect. In contrast only beta-glucans from two species of macrofungi were able to
      interfere with interaction of C5 with the FIMs of C7.

PMID- 28757373
TI  - Anti-inflammatory mechanism of galangin in lipopolysaccharide-stimulated
      microglia: Critical role of PPAR-gamma signaling pathway.
AB  - Since microglia-associated neuroinflammation plays a pivotal role in the
      progression of neurodegenerative diseases, controlling microglial activation has
      been suggested as a potential therapeutic strategy. Here, we investigated the
      anti-inflammatory effects of galangin (3,5,7-trihydroxyflavone) in microglia and
      analyzed the underlying molecular mechanisms. Galangin inhibited the expression
      of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines and
      enhanced the expression of anti-inflammatory interleukin (IL)-10 in
      lipopolysaccharide (LPS)-stimulated BV2 microglia. Galangin also suppressed
      microglial activation and the expression of pro-inflammatory markers in LPS
      injected mouse brains. The results of mechanistic studies have shown that
      galangin inhibited LPS-induced phosphorylation of p38 mitogen activated protein
      kinase (MAPK), c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase
      (PI3K)/Akt, and nuclear factor (NF)-kappaB activity. On the contrary, galangin
      increased the activity of transcription factors, such as nuclear factor-E2
      related factor 2 (Nrf2), cAMP response element-binding protein (CREB), and
      peroxisome proliferator-activated receptor (PPAR)-gamma, known to play an anti
      inflammatory role. In addition, galangin showed antioxidant effects by
      suppressing the expression of NADPH oxidase subunits p47phox and gp91phox, and by
      enhancing hemeoxygenase-1. We then investigated whether PPAR-gamma was involved
      in the anti-inflammatory function of galangin. Pretreatment with a PPAR-gamma
      antagonist or siRNA significantly blocked galangin-mediated upregulation of IL-10
      and attenuated the inhibition of tumor necrosis factor (TNF)-alpha, nitric oxide
      (NO), and IL-6 in LPS-stimulated microglia. Moreover, the PPAR-gamma antagonist
      reversed the effects of galangin on NF-kappaB, Nrf2, and CREB. Altogether, our
      data suggest that PPAR-gamma plays a key role in mediating the anti-inflammatory
      effects of galangin by modulating the NF-kappaB and Nrf2/CREB signaling pathways.

PMID- 28757374
TI  - Trait level analysis of multitrait population projection matrices.
AB  - In most matrix population projection models, individuals are characterized
      according to, usually, one or two traits such as age, stage, size or location. A
      broad theory of multitrait population projection matrices (MPPMs) incorporating
      larger number of traits was long held back by time and space computational
      complexity issues. As a consequence, no study has yet focused on the influence of
      the structure of traits describing a life-cycle on population dynamics and life
      history evolution. We present here a novel vector-based MPPM building methodology
      that allows to computationally-efficiently model populations characterized by
      numerous traits with large distributions, and extend sensitivity analyses for
      these models. We then present a new method, the trait level analysis consisting
      in folding an MPPM on any of its traits to create a matrix with alternative trait
      structure (the number of traits and their characteristics) but similar asymptotic
      properties. Adding or removing one or several traits to/from the MPPM and
      analyzing the resulting changes in spectral properties, allows investigating the
      influence of the trait structure on the evolution of traits. We illustrate this
      by modeling a 3-trait (age, parity and fecundity) population designed to
      investigate the implications of parity-fertilitytrade-offs in a context of
      fecundity heterogeneity in humans. The trait level analysis, comparing models of
      the same population differing in trait structures, demonstrates that fertility
      selection gradients differ between cases with or without parity-fertility trade
      offs. Moreover it shows that age-specific fertility has seemingly very different
      evolutionary significance depending on whether heterogeneity is accounted for.
      This is because trade-offs can vary strongly in strength and even direction
      depending on the trait structure used to model the population.

PMID- 28757376
TI  - Tobacco companies flout anti-tobacco laws in India.

PMID- 28757377
TI  - Redefining the molecular substructure of medulloblastoma.

PMID- 28757378
TI  - The true value of altered fractionation in head and neck cancer.

PMID- 28757379
TI  - Concurrent chemotherapy and proton beam therapy in NSCLC.

PMID- 28757380
TI  - High acute:chronic workloads are associated with injury in England & Wales
      Cricket Board Development Programme fast bowlers.
AB  - OBJECTIVES: The objectives of this study were to explore the relationship between
      acute (1 week) and chronic (4-week average) bowling workloads and injury risk in
      National Development Programme fast bowlers, and to investigate individual
      differences in the relationship between acute:chronic workloads and injury.
      DESIGN: Prospective cohort study. METHODS: Bowling workloads and injury data were
      collected prospectively for 29 male fast bowlers (age range 15-18) on a National
      Programme over two years. Workload variables were calculated and the likelihood
      of injury and individual effects were explored using a generalised linear mixed
      effects model and magnitude-based inferences. RESULTS: Acute:chronic workloads of
      109-142% (relative risk [RR]: 1.46, 90% CI: 0.93-2.29; likely harmful), and
      >=142% (RR: 1.66, 90% CI: 1.06-2.59, likely harmful) were associated with a
      substantial increase in injury risk compared with the reference quartile (<87%).
      A high chronic workload (>83 balls) substantially attenuated the influence of a
      high (>108%) acute:chronic workload ratio on injury risk (RR: 0.35, 90% CI: 0.17
      0.74). Significant individual differences in the acute:chronic workload-injury
      relationship were evident. CONCLUSIONS: The present study provides further
      evidence of the association between 'spikes' in workload and injury risk, but
      also demonstrates that this relationship is individual-specific and dependent on
      the level of chronic workload. Support teams for fast bowlers should monitor
      bowling workloads to avoid rapid fluctuations but should also base decisions on
      individualised data.

PMID- 28757375
TI  - Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated
      meta-analysis.
AB  - BACKGROUND: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head
      and neck (MARCH) showed that altered fractionation radiotherapy is associated
      with improved overall and progression-free survival compared with conventional
      radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit.
      This update aims to confirm and explain the superiority of hyperfractionated
      radiotherapy over other altered fractionation radiotherapy regimens and to assess
      the benefit of altered fractionation within the context of concomitant
      chemotherapy with the inclusion of new trials. METHODS: For this updated meta
      analysis, we searched bibliography databases, trials registries, and meeting
      proceedings for published or unpublished randomised trials done between Jan 1,
      2009, and July 15, 2015, comparing primary or postoperative conventional
      fractionation radiotherapy versus altered fractionation radiotherapy (comparison
      1) or conventional fractionation radiotherapy plus concomitant chemotherapy
      versus altered fractionation radiotherapy alone (comparison 2). Eligible trials
      had to start randomisation on or after Jan 1, 1970, and completed accrual before
      Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge
      of treatment assignment; and had to include patients with non-metastatic squamous
      cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing
      first-line curative treatment. Trials including a non-conventional radiotherapy
      control group, investigating hypofractionated radiotherapy, or including mostly
      nasopharyngeal carcinomas were excluded. Trials were grouped in three types of
      altered fractionation: hyperfractionated, moderately accelerated, and very
      accelerated. Individual patient data were collected and combined with a fixed
      effects model based on the intention-to-treat principle. The primary endpoint was
      overall survival. FINDINGS: Comparison 1 (conventional fractionation radiotherapy
      vs altered fractionation radiotherapy) included 33 trials and 11 423 patients.
      Altered fractionation radiotherapy was associated with a significant benefit on
      overall survival (hazard ratio [HR] 0.94, 95% CI 0.90-0.98; p=0.0033), with an
      absolute difference at 5 years of 3.1% (95% CI 1.3-4.9) and at 10 years of 1.2% (
      0.8 to 3.2). We found a significant interaction (p=0.051) between type of
      fractionation and treatment effect, the overall survival benefit being restricted
      to the hyperfractionated group (HR 0.83, 0.74-0.92), with absolute differences at
      5 years of 8.1% (3.4 to 12.8) and at 10 years of 3.9% (-0.6 to 8.4). Comparison 2
      (conventional fractionation radiotherapy plus concomitant chemotherapy versus
      altered fractionation radiotherapy alone) included five trials and 986 patients.
      Overall survival was significantly worse with altered fractionation radiotherapy
      compared with concomitant chemoradiotherapy (HR 1.22, 1.05-1.42; p=0.0098), with
      absolute differences at 5 years of -5.8% (-11.9 to 0.3) and at 10 years of -5.1%
      (-13.0 to 2.8). INTERPRETATION: This update confirms, with more patients and a
      longer follow-up than the first version of MARCH, that hyperfractionated
      radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for
      the treatment of locally advanced head and neck squamous cell cancers. The
      comparison between hyperfractionated radiotherapy and concomitant
      chemoradiotherapy remains to be specifically tested. FUNDING: Institut National
      du Cancer; and Ligue Nationale Contre le Cancer.

PMID- 28757381
TI  - Using the capture-recapture method to estimate the incidence of musculoskeletal
      injuries among U.S. Army soldiers.
AB  - : Musculoskeletal injury (MSI) data typically are obtained from medical chart
      review (MCR) or injury self-reports (ISR). MSI incidence may be under-counted if
      only one source is utilized, as MCR will not capture MSI for which medical care
      was not sought, and ISR may be affected by issues with recall. OBJECTIVES: The
      purposes of this study were to determine MSI incidence from two sources (MCR,
      ISR) and to estimate the incidence, after accounting for the under-counting in
      both sources, among a sample of U.S. Army soldiers. DESIGN: Descriptive cross
      sectional study. METHODS: The estimated cumulative incidence during a one-year
      period was calculated from the two sources of MSI data using a novel statistical
      analysis (capture-recapture-CRC). RESULTS: MSI data were available for 287
      soldiers (age: 27.5+/-6.3years (mean+/-standard deviation)). The one-year
      cumulative incidence of MSI was 17.8% (MCR), 19.5% (ISR), and 54.0% (CRC). CRC
      analysis showed that there was under-counting from both sources of data and the
      percent of CRC estimated MSI observed were 32.9% (MCR), 36.1% (ISR), and 57.4%
      (MCR and ISR combined). When analyzed by MSI type, percent of CRC estimated MSI
      counted from both sources was highest (75.0%) for fracture, followed by sprain
      (53.8%), strain (43.8%), and pain/spasm/ache (35.8%). CONCLUSIONS: There was
      under-counting of MSI from both sources of data, and the under-counting varied by
      MSI type. There is a need for further investigation of the relative benefits of
      various sources of MSI data and the application of the capture-recapture analysis
      in military populations.

PMID- 28757382
TI  - Editorial.

PMID- 28757383
TI  - Indications and outcome of splenectomy in hematologic disease.
AB  - Splenectomy is part of the therapeutic arsenal for benign or malignant
      hematological disorders that constitute the main indication for elective
      splenectomy. With the development of minimally invasive approaches, and in
      particular, laparoscopy, as well as the advent of monoclonal antibody therapy,
      the indications and the outcomes of splenectomy for hematologic disease have
      changed in recent years. Nonetheless, splenectomy has its place in
      hemoglobinopathies and hemolytic diseases, improves thrombocytopenia in
      refractory immune thrombocytopenic purpura, can reverse sequelae linked to
      voluminous splenomegaly secondary to myelofibrosis, or can be used for diagnostic
      purposes or for splenomegaly in lymphoproliferative syndromes.

PMID- 28757384
TI  - ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA
      binding.
AB  - Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by
      p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509
      primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L,
      resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by
      activating p21/CDKN1A and RB transcription, respectively. When cells are exposed
      to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis)
      transcription. Interestingly, apoptosis due to transcriptional activation of PUMA
      by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s)
      underlying the transcriptional attenuation and anti-apoptotic effects of
      ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA
      gene transcription by modulating post-translational modification of p53 by p300.
      ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of
      p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding
      at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not
      only in cell cycle arrest, by activating RB expression, but also in rescuing
      cells from apoptotic death by repressing PUMA expression in cells exposed to
      severe DNA damage.

PMID- 28757385
TI  - Trueness and precision of the real-time RT-PCR method for quantifying the chronic
      bee paralysis virus genome in bee homogenates evaluated by a comparative inter
      laboratory study.
AB  - The Chronic bee paralysis virus (CBPV) is the aetiological agent of chronic bee
      paralysis, a contagious disease associated with nervous disorders in adult
      honeybees leading to massive mortalities in front of the hives. Some of the
      clinical signs frequently reported, such as trembling, may be confused with
      intoxication syndromes. Therefore, laboratory diagnosis using real-time PCR to
      quantify CBPV loads is used to confirm disease. Clinical signs of chronic
      paralysis are usually associated with viral loads higher than 108 copies of CBPV
      genome copies per bee (8 log10 CBPV/bee). This threshold is used by the European
      Union Reference Laboratory for Bee Health to diagnose the disease. In 2015, the
      accuracy of measurements of three CBPV loads (5, 8 and 9 log10 CBPV/bee) was
      assessed through an inter-laboratory study. Twenty-one participants, including 16
      European National Reference Laboratories, received 13 homogenates of CBPV
      infected bees adjusted to the three loads. Participants were requested to use the
      method usually employed for routine diagnosis. The quantitative results (n=270)
      were analysed according to international standards NF ISO 13528 (2015) and NF ISO
      5725-2 (1994). The standard deviations of measurement reproducibility (SR) were
      0.83, 1.06 and 1.16 at viral loads 5, 8 and 9 log10 CBPV/bee, respectively. The
      inter-laboratory confidence of viral quantification (+/- 1.96SR) at the
      diagnostic threshold (8 log10 CBPV/bee) was+/- 2.08 log10 CBPV/bee. These results
      highlight the need to take into account the confidence of measurements in
      epidemiological studies using results from different laboratories. Considering
      this confidence, viral loads over 6 log10 CBPV/bee may be considered to indicate
      probable cases of chronic paralysis.

PMID- 28757386
TI  - Competitive enzyme-linked immunosorbent assay using baculovirus-expressed VP7 for
      detection of epizootic haemorrhagic disease virus (EHDV) antibodies.
AB  - Epizootic haemorrhagic disease (EHD) is a vector-borne infectious viral disease
      of domestic and wild ruminants. EHD could spread from infected northern African
      countries in free territories like the EU; therefore, the availability of
      diagnostic assays would represent key components for adequate surveillance and
      control programs. In this study, the gene encoding the VP7 protein of EHD virus
      (EHDV) was expressed into a baculovirus-infected insect cell system. With this
      unpurified protein we developed a home-made competitive ELISA (cELISA) and a
      total number of 275 serum samples, originating from domestic and wild ruminants,
      were tested. 74/275 were previously shown to be positive for EHDV antibodies by a
      commercially available ELISA kit. A "very good" agreement was demonstrated when
      compared to a commercial ELISA kit (Cohen's kappa value=0.832). Samples which
      caused disagreement between the two assays originated from wildlife which
      highlights the need for further validation by using serum samples from wild
      animals.

PMID- 28757387
TI  - A fast PCR-based method for the characterization of prophage profiles in strains
      of the Lactobacillus casei group.
AB  - Lysogeny is widespread among Lactobacillus strains of the casei group (L. casei,
      L. paracasei and L. rhamnosus), and prophages account for most strain-specific
      DNA. Numerous PCR based methods have been developed to detect free phages of
      lactic acid bacteria, but they do not take in consideration prophages. In this
      study, a new PCR method for the detection of lysogeny was developed using genome
      sequences of L. casei group strains (including BL23) and bacteriophages. Nine
      pairs of primers were designed to selectively amplify the highly conserved
      prophage iA2 (pairs #1-#3) and fragments of two groups phages of temperate
      origin: CL1/CL2/iLp1308/iLp84 (pairs #4 and #5) and Lrm1/J-1/PL-1/A2/AT3/Lc-Nu
      (pairs #6 to #9). Forty-nine strains of the casei group were subjected to PCR.
      Strains containing remnants of lytic phages outnumbered those containing iA2
      related prophages. The combination of pair #2, annealing on the terminase large
      subunit (TLS), and pair #3, annealing on the helicase (forward) and a non-coding
      region (reverse), showed the best diagnostic performance for iA2-like prophages.
      For the assessment of remnants of phages CL1/CL2/iLp1308/iLp84, pair #4
      (annealing on the TLS) was preferred over pair #5 (portal protein). Detection of
      phages Lrm1/J-1/PL-1/A2/AT3/Lc-Nu was optimal with primers of pair #6, designed
      on non-coding regions of phage genomes; pair #6 also evidenced a high
      conservation of certain prophage remnants. Overall, our PCR-based method
      successfully detected and discriminated groups of prophages or remnants in L.
      casei group strains.

PMID- 28757388
TI  - Effects of single or combined induction of diabetes mellitus and knee
      osteoarthritis on some biochemical and haematological parameters in rats.
AB  - Clinical evidences on the coexistence of diabetes mellitus (DM) and
      osteoarthritis (OA) dated back to the 1960s. Therefore, the study investigated
      the effects of induced DM and/or knee osteoarthritis (KOA) on some biochemical
      and haematological parameters in adult male Wistar rats. Twenty rats were used
      for this study. They were randomly divided into 4 groups (N=5 rats) which
      included: Normal control; Osteoarthritic (OA) control; Diabetic control; and,
      Diabetic+Osteoarthritic (D+OA) control. DM was induced in overnight fasted rats
      by the administration of streptozotocin (65mg/kg b.w., i.p.) 15min after the
      administration of nicotinamide (110mg/kg, b.w., i.p.). However, KOA was induced
      by the intra-articular injection of 4mg of sodium monoiodoacetate in 40MUl of
      normal saline. In the D+OA group, KOA was induced about 12h after the induction
      of DM. The rats were left untreated for four weeks. Afterwards, the experiment
      was terminated. The results showed that both DM and OA featured hypercortisolism
      and dyslipidaemia. The additive effects of both conditions were observed on the
      lipid profile and some haematological indices in the D+OA group. Unlike DM, OA
      had mild adverse effects on the haematological profile. Nevertheless, it
      significantly contributed to hyperglycaemia in the D+OA group, even though it had
      no significant effect on the insulin resistance. However, the hypocalcaemic and
      glycogenolytic effects of DM were negated by OA. In conclusion, the coexistence
      of DM and OA presents a greater challenge on the biochemical and haematological
      profiles than the individual disease. But, this prediction could sometimes be
      annulled by the intervention of endogenous homeostatic mechanisms.

PMID- 28757389
TI  - Spatial organization of genome architecture in neuronal development and disease.
AB  - Although mammalian genomes encode genetic information in their linear sequences,
      their fundamental function with regard to gene expression depends on the higher
      order structure of chromosomes. Current techniques for the evaluation of
      chromosomal structure have revealed that genomes are arranged at several
      hierarchical levels in three-dimensional space. The spatial organization of
      genomes involves the formation of chromatin loops that bypass a wide range of
      genomic distances, providing a connection between enhancers and chromosomal
      domains. Furthermore, they form chromatin domains that are arranged into
      chromosome territories in the three-dimensional space of the cell nucleus. Recent
      studies have shown that the spatial organization of the genome is essential for
      normal brain development and function. Activity-dependent alterations in the
      spatial organization of the genome can regulate transcriptional activity related
      to neuronal plasticity. Disruptions in the higher-order chromatin architecture
      have been implicated in neuropsychiatric disorders, such as cognitive dysfunction
      and anxiety. Here, we discuss the growing interest in the role of genome
      organization in brain development and neurological disorders.

PMID- 28757390
TI  - Prediction of autonomic neuropathy in chronic kidney disease (stage 5) Iraqi
      patients (case control study).
AB  - BACKGROUND: The presence of autonomic neuropathy in association with end stage
      chronic kidney disease have not yet been established. An extending studies need
      to evaluate the presence of autonomic neuropathy in different stages of chronic
      kidney disease. OBJECTIVES: To estimate the prevalence rate of autonomic
      neuropathy in stage 5 chronic kidney disease. METHODS: 35 patients with end stage
      CKD were selected (patient group), compared with 100 person had CKD of different
      stages other than stage 5 CKD (control group). A sequence of questionnaires (6
      questions) were applied to both groups, followed by testing for postural
      hypotension using as a complementary test for ANP with the cold immersion test.
      Any subject failed to show an increment in BP was labeled as having test positive
      and hence having ANP. RESULTS: The distribution of ANP according to the
      questionnaire was higher in the patient's group than the controls (p<0.0001).
      Postural hypotension was more in patients versus the control (p 0.026). The Cold
      immersion test was positive in 23 subject in patients (65.7%) than the control
      only 11 subject (11%), (p<0.0001).

PMID- 28757391
TI  - Systemic dexmedetomidine attenuates mechanical allodynia through extracellular
      sign db type 2 diabetic mice.
AB  - Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus.
      However, the treatment for PDN is limited in clinical practice. In the present
      study, we investigated the effect of systemic administration dexmedetomidine
      (DEX), a selective alpha 2 adrenergic receptor (alpha2AR) agonist, on mechanical
      allodynia and its underlying mechanism in db/db mice, an animal model of type 2
      diabetes mellitus. Our data demonstrated that db/db mice develop mechanical
      allodynia at the early stage of diabetes. During the period of mechanical
      allodynia, we detected increased release of norepinephrine (NE) and decreased
      levels of alpha2A-Adrenoceptors in db/db mice. Immunohistochemistry showed that
      the alpha2A-Adrenoceptor is predominantly expressed in neurons in the spinal
      cord. Acute injection of dexmedetomidine significantly decreased mechanical
      allodynia, which was blocked by its selective antagonist BRL44408. Furthermore,
      the upregulation of pERK1 and pERK2 in db/db mice were attenuated by
      preadministration of dexmedetomidine. We provide the first evidence that the
      functional alternation of spinal noradrenergic system might underlie exaggerated
      nociception in PDN. Systemic dexmedetomidine inhibits the mechanical allodynia
      which is related to ERK signaling pathway in type 2 diabetes, implying that the
      alpha2-Adrenoceptor might be a potential therapeutic strategy for PDN.

PMID- 28757392
TI  - Extending the family: Roles for uptake2 transporters in regulation of
      monoaminergic signaling.

PMID- 28757393
TI  - A comparative study on the anti-schistosomal and hepatoprotective effects of
      vinpocetine and isosorbide-5-mononitrate on Schistosoma mansoni-infected mice.
AB  - Schistosomiasis is a remarkable public health problem in developing countries.
      Presently, praziquantel is the optional drug for all human schistosomiasis. Owing
      to the increased praziquantel resistance, there is an urgent need to develop new
      alternatives. This study aims at determining the anti-schistosomal and/or the
      hepatoprotective effects of the anti-inflammatory drug; vinpocetine, and the
      vasodilator and the nitric oxide donor; isosorbide-5-mononitrate, in comparison
      to praziquantel. In the present research, the therapeutic efficacies of these
      drugs were assessed in Swiss albino female mice (CD-I strain) experimentally
      infected with an Egyptian strain of Schistosoma mansoni, using some general,
      parasitological, and histopathological parameters. In this work, praziquantel
      significantly reduced worm burden and hepatic egg load, increased the percentage
      of dead eggs in the small intestine and decreased granuloma count, but did not
      reduce granuloma diameter. While, either vinpocetine or isosorbide-5-mononitrate
      monotherapy did not induce significant reduction in the worm count, hepatic egg
      load or shift in the oogram pattern, but significantly reduced granuloma count
      and diameter. Moreover, isosorbide-5-mononitrate significantly reduced hepatic
      inflammation and necrosis. The best results were obtained in the mice groups
      treated with isosorbide-5-mononitrate combined with praziquantel or vinpocetine.
      Our results point to vinpocetine and isosorbide-5-mononitrate as a convenient and
      promising adjuvant to praziquantel for ameliorating schistosomal liver pathology.
      Further studies are recommended to reveal the actual pathways responsible for the
      different activities of vinpocetine and isosorbide-5-mononitrate.

PMID- 28757394
TI  - Broad-spectrum non-nucleoside inhibitors for caliciviruses.
AB  - Viruses of the Caliciviridae cause significant and sometimes lethal diseases,
      however despite substantial research efforts, specific antivirals are lacking.
      Broad-spectrum antivirals could combat multiple viral pathogens, offering a rapid
      solution when no therapies exist. The RNA-dependent RNA polymerase (RdRp) is an
      attractive antiviral target as it is essential for viral replication and lacks
      mammalian homologs. To focus the search for pan-Caliciviridae antivirals, the
      RdRp was probed with non-nucleoside inhibitors (NNIs) developed against hepatitis
      C virus (HCV) to reveal both allosteric ligands for structure-activity
      relationship enhancement, and highly-conserved RdRp pockets for antiviral
      targeting. The ability of HCV NNIs to inhibit calicivirus RdRp activities was
      assessed using in vitro enzyme and murine norovirus cell culture assays. Results
      revealed that three NNIs which bound the HCV RdRp Thumb I (TI) site also
      inhibited transcriptional activities of six RdRps spanning the Norovirus,
      Sapovirus and Lagovirus genera of the Caliciviridae. These NNIs included JTK-109
      (RdRp inhibition range: IC50 4.3-16.6 MUM), TMC-647055 (IC50 range: 18.8-45.4
      MUM) and Beclabuvir (IC50 range: 23.8->100 MUM). In silico studies and site
      directed mutagenesis indicated the JTK-109 binding site was within the
      calicivirus RdRp thumb domain, in a pocket termed Site-B, which is highly
      conserved within all calicivirus RdRps. Additionally, RdRp inhibition assays
      revealed that JTK-109 was antagonistic with the previously reported RdRp
      inhibitor pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate)
      tetrasodium salt (PPNDS), that also binds to Site-B. Moreover, like JTK-109,
      PPNDS was also a potent inhibitor of polymerases from six viruses spanning the
      three Caliciviridae genera tested (IC50 range: 0.1-2.3 MUM). Together, this study
      demonstrates the potential for de novo development of broad-spectrum antivirals
      that target the highly-conserved RdRp thumb pocket, Site-B. We also revealed
      three broad-spectrum HCV NNIs that could be used as antiviral scaffolds for
      further development against caliciviruses and other viruses.

PMID- 28757395
TI  - Experimental characterization of the biaxial mechanical properties of porcine
      gastric tissue.
AB  - Health problems related to the stomach are among the most important sources of
      morbidity in industrialized countries. There is evidence that mechanics may play
      an important role in various such pathologies. However, so far experimental data
      characterizing the mechanical properties of gastric tissue remain scarce, which
      significantly limits our understanding of the mechanics of the stomach. To help
      close this gap, we performed biaxial mechanical tests of porcine gastric tissue
      patches. Our experiments reveal a considerable anisotropy and different
      mechanical properties in the three major regions of the stomach (fundus, corpus,
      antrum). Moreover, they demonstrate that the mechanical properties of the gastric
      wall and the physiological function of the different regions of the stomach are
      closely related. This finding suggests that further examination of the mechanics
      of the gastric wall may indeed be a promising avenue of research towards a better
      understanding of the organic causes of frequent health problems related to the
      stomach.

PMID- 28757396
TI  - Impact of the SCARE guideline on the reporting of surgical case reports: A before
      and after study.
AB  - INTRODUCTION: The SCARE guideline was developed in 2016 through an expert Delphi
      consensus exercise. It aimed to improve the quality of reporting of surgical case
      reports. The aim of this study was to assess the impact of introducing the SCARE
      guideline for surgical on reporting of case reports submitted to a single
      journal. METHODS: A total of 20 case reports published in the International
      Journal of Surgery Case Reports (IJSCR) and Annals of Medicine and Surgery (AMS)
      in July and August 2016, prior to the introduction of the SCARE guideline (the
      pre-SCARE period), were randomly identified and scored against the SCARE
      criteria. Two independent teams performed the scoring giving a total score out of
      a theoretical maximum of 34 for each case report, the 'SCARE score' (expressed as
      a percentage). The scores for the two teams were then compared and consensus was
      reached to achieve a final sore set. This process was repeated for the January
      and February 2017 issues of the journal, post implementation of the guideline
      (the post-SCARE period). SCARE scores were compared between the pre- and post
      SCARE periods. RESULTS: The mean pre-SCARE score was 75.0% (standard deviation +/
      6.29, Range 62-84), and the mean post-SCARE score was 82.6% (standard deviation
      +/- 8.02, range 66-99), a 10% relative increase in compliance which was
      statistically significant (P < 0.001). The Cohen's Kappa score between teams A
      and B was 0.871, implying very substantial agreement. CONCLUSION: Implementation
      of the SCARE guideline resulted in a 10% improvement in the reporting quality of
      surgical case reports published in a single journal. Adherence to SCARE reporting
      guidelines by authors, reviewers and editors should be improved to boost
      reporting quality. Journals should develop their policies, submission processes
      and guide for authors to incorporate the guideline.

PMID- 28757397
TI  - Low utility of serum 25-hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3 in
      predicting peripheral Treg and Th17 cell counts in ESRD and renal transplant
      patients.
AB  - BACKGROUND: Vitamin D has shown an immune-modulatory effect in different studies.
      Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of
      vitamin D in chronic kidney disease (CKD) and renal transplant patients is
      unclear. We measured whether different serum levels of vitamin D were associated
      with an increased or decreased presence of lymphocyte subsets including Treg and
      Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients.
      METHODS: Eighty-seven renal transplant recipients and 53 end-stage renal disease
      (ESRD) patients were enrolled in this study. The absolute counts of CD4+ and CD8+
      T, CD16+ CD56+ NK, CD19+ B, CD4+ CD25+ CD127- Foxp3+ (Tregs), Helios+ Tregs,
      CD38+ Tregs, and CD4+ CD17+ (Th17) cells were analyzed in peripheral blood in
      both patient groups. In addition, serum 25 (OH) D3, 1, 25 (OH)2 D3, IL-6, IL-17,
      IL-23, and TGF-beta1 were measured. The association between lymphocyte subset
      counts and 1, 25 (OH)2 D3 or 25 (OH) D3 was studied, as was the association
      between serum IL-6, IL-17, IL-23, or TGF-beta1 and 1,25 (OH)2 D3 or 25 (OH) D3.
      RESULTS: Serum 25 (OH) D3 and 1,25 (OH)2 D3 levels were not independently
      associated with peripheral CD4+ T, CD19+ B, CD16+ CD56+ NK, Treg, or Th17 cell
      counts. In contrast to serum 25 (OH) D3, serum1, 25 (OH)2 D3 was positively
      associated with CD8+ T cells counts in renal transplant recipients. CONCLUSION:
      Our findings indicate low utility of serum 25 (OH) D3 and 1, 25 (OH)2 D3 levels
      in predicting a change in lymphocyte subset counts in ESRD and renal transplant
      patients.

PMID- 28757399
TI  - Diabetic retinopathy, an overview.
AB  - This overview introduces contributions to a special issue on causes of vision
      loss from diabetes mellitus, focusing on the retina and also the cornea. Diabetic
      retinopathy is the most common and leading cause of vision loss among people with
      diabetes. Research to detect early symptoms, understand mechanisms leading to
      diabetic eye disease, and the development of treatments is a highly active
      research area, with currently about 2000 scientific publication per year. We
      provide a series of 27 comprehensive reviews and research articles from leading
      experts in the field.

PMID- 28757398
TI  - High expression of TIM-3 and KIM-1 in blood and urine of renal allograft
      rejection patients.
AB  - BACKGROUND: T cell immunoglobulin and mucin domain 3 (TIM-3) is involved in
      alloimmune and autoimmune responses, as well as tolerance induction in kidney
      transplantation. Kidney injury molecule-1 (KIM-1) is highly expressed in
      epithelial cells of the injured proximal tubule. In this study, we have
      investigated both urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA
      expression, and urinary and serum KIM-1 proteins in renal allograft recipients
      diagnosed with acute allograft rejection (AR) and chronic allograft dysfunction
      (CAD), as well as those with well-functioning transplants (WFG). METHODS: We
      divided 85 patients into the following groups: AR (n=24), CAD (n=19), and WFG
      (n=42). TIM-3 and KIM-1 mRNA expressions were quantified using real-time reverse
      transcription TaqMan probe polymerase chain reaction (RT-PCR). An ELISA test was
      used to measure the amount of KIM-1 protein in serum and urine samples. RESULTS:
      AR and CAD patients had significantly greater urinary and blood TIM-3 mRNA
      expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins
      compared to WFG patients. Receiver operating characteristic (ROC) analysis showed
      that these molecules discriminated Allograft rejections from WFG. CONCLUSION:
      Quantification of TIM-3 and KIM-1 mRNA expressions, along with KIM-1 protein
      measurements in urine and blood could be employed as promising tools for
      noninvasive diagnosis of allograft dysfunction.

PMID- 28757400
TI  - Epigenetic regulation of EC-SOD expression in aging lung fibroblasts: Role of
      histone acetylation.
AB  - Lung disorders characterized by fibroproliferation and excessive deposition of
      extracellular matrices occur in late adulthood, and their pathological
      manifestations become more prominent with aging. The exact mechanisms linking
      aging and fibroproliferative disorders are unknown, but increased oxidative
      stress resulting in the accumulation of damaged proteins, DNA, and lipids is
      considered a major factor. In the lung, and especially in the pulmonary
      fibroblasts, the extracellular superoxide dismutase (EC-SOD) is a major
      antioxidant enzyme that has been implicated in pulmonary fibrosing disorders,
      among others. Here, we investigate the regulation of EC-SOD in pulmonary lung
      fibroblasts derived from young (up to 3 month) and old (24 month) C57BL6 mice. We
      found that old fibroblasts have marginally elevated levels of reactive oxidant
      species (ROS), which coincides with attenuated expression a number of antioxidant
      enzymes including EC-SOD. Exposure of old fibroblasts to the DNA
      methyltransferase inhibitor 5-aza-dC did not restore expression of EC-SOD. On the
      other hand, repression of EC-SOD expression was associated with deacetylation of
      lysine 9 on histone H3 and lysines 5, 8, 12 and 16 on histone H4 located at the
      gene promoter. Interestingly, the repressive tri-methylation of lysine 27 on
      histone H3 was elevated in old compared to young fibroblasts. In addition,
      exposure of old lung fibroblasts to HDAC class 1 and class 2 inhibitors restored
      EC-SOD expression to the level observed in young fibroblasts. While the exact
      mechanism of age-dependent downregulation of EC-SOD is yet to be defined, our
      studies indicate a potential role of epigenetic mechanisms including histone
      deacetylation in this process.

PMID- 28757401
TI  - Impact of adjuvant systemic chemotherapy on wound healing and cosmetic outcome in
      224 women treated with accelerated partial breast irradiation using interstitial
      brachytherapy.
AB  - PURPOSE: To evaluate the impact of timing of adjuvant chemotherapy on wound
      healing and cosmetic outcome in women treated with accelerated partial breast
      irradiation (APBI). METHODS AND MATERIALS: Between August 2000 to December 2011,
      224 women were treated with APBI using multicatheter interstitial high-dose-rate
      brachytherapy. Patients were treated to a dose of 34 Gy/10#/5-7 days with bid
      regimen. Systemic chemotherapy was administered as per the standard guidelines.
      RESULTS: Multicatheter interstitial brachytherapy technique was open cavity in
      136 (60%) and closed cavity in 88 (40%). Adjuvant chemotherapy was given in 117
      (52%). Wound complications (WCs) were observed in 24 patients (11%), which
      included wound infections (WIs) in 20 and wound dehiscence in 14. The median gap
      between chemotherapy and APBI was 13 days in women who developed WCs, 20 days for
      prechemo, and 32 days for postchemo APBI in its absence. On multivariate
      analysis, gap between APBI and chemotherapy of <=3 weeks was the only significant
      factor (p = 0.03) affecting WCs. Acute WI (p = 0.01) and two-dimensional planning
      (p = 0.04) had significant impact on cosmesis resulting in fair to poor cosmetic
      outcome. CONCLUSIONS: Gap of <=3 weeks between APBI and chemotherapy resulted in
      increased WCs. WI and two-dimensional planning resulted in poorer cosmetic
      outcome. We recommend gap of at least 3 weeks for optimal outcome.

PMID- 28757402
TI  - Brachytherapy patient safety events in an academic radiation medicine program.
AB  - PURPOSE: To describe the incidence and type of brachytherapy patient safety
      events over 10 years in an academic brachytherapy program. METHODS AND MATERIALS:
      Brachytherapy patient safety events reported between January 2007 and August 2016
      were retrieved from the incident reporting system and reclassified using the
      recently developed National System for Incident Reporting in Radiation Treatment
      taxonomy. A multi-incident analysis was conducted to identify common themes and
      key learning points. RESULTS: During the study period, 3095 patients received
      4967 brachytherapy fractions. An additional 179 patients had MR-guided prostate
      biopsies without treatment as part of an interventional research program. A total
      of 94 brachytherapy- or biopsy-related safety events (incidents, near misses, or
      programmatic hazards) were identified, corresponding to a rate of 2.8% of
      brachytherapy patients, 1.7% of brachytherapy fractions, and 3.4% of patients
      undergoing MR-guided prostate biopsy. Fifty-one (54%) events were classified as
      actual incidents, 29 (31%) as near misses, and 14 (15%) as programmatic hazards.
      Two events were associated with moderate acute medical harm or dosimetric
      severity, and two were associated with high dosimetric severity. Multi-incident
      analysis identified five high-risk activities or clinical scenarios as follows:
      (1) uncommon, low-volume or newly implemented brachytherapy procedures, (2) real
      time MR-guided brachytherapy or biopsy procedures, (3) use of in-house devices or
      software, (4) manual data entry, and (5) patient scheduling and handoffs.
      CONCLUSIONS: Brachytherapy is a safe treatment and associated with a low rate of
      patient safety events. Effective incident management is a key element of
      continuous quality improvement and patient safety in brachytherapy.

PMID- 28757403
TI  - Performance of a palladium-103 line source for prostate brachytherapy implants: A
      Phase I trial.
AB  - PURPOSE: To evaluate the use of a polymer-encapsulated palladium-103 (103 Pd)
      source with a unique linear radioactive distribution in prostate brachytherapy.
      This feasibility study assessed dosimetry, ease and efficiency of use, and side
      effects. The number of needles required for adequate coverage was the primary end
      point. METHODS AND MATERIALS: CivaString 103 Pd Model CS10 implants were
      preplanned for 25 patients. CivaStrings were custom manufactured according to
      plan. CivaStrings were implanted with 18 gauge needles. Post-implant dosimetry
      was performed at 3-6 weeks. RESULTS: Monotherapy (125 Gy) was prescribed for 11
      implants. External beam radiation with CivaString boost (100 Gy) was prescribed
      for 14 implants. The mean time to implant the sources was 23.5 min. The number of
      planned needles and prostate sizes ranged from 14 to 25 and 21-101 cm3,
      respectively. 70% of implants in prostates less than 50 cm3 required <=17
      needles. Planned source strength ranged from 2.8 U/cm to 3.9 U/cm. Total source
      strength averaged 216 U (130-323 U) for monotherapy and 154 U (92.4-245 U) for
      boost. Nomograms were generated at both prescription dose levels. CONCLUSIONS:
      The linear 103Pd source provides good dose coverage to the prostate. Prostate
      volume changes were minimal suggesting minimal swelling using the CivaString
      device.

PMID- 28757404
TI  - Intermediate dose-volume parameters and the development of late rectal toxicity
      after MRI-guided brachytherapy for locally advanced cervix cancer.
AB  - PURPOSE: The dose delivered to the most exposed 2 cm3 [Formula: see text] of the
      rectum and bladder is predictive of late rectal and bladder toxicity in cervix
      cancer patients. We investigated the predictive value of intermediate doses to
      the rectum and bladder for late rectal/bladder toxicity after MRI-guided
      brachytherapy for patients with locally advanced cervix cancer. METHODS AND
      MATERIALS: Toxicity was prospectively graded using Common Toxicity Criteria for
      Adverse Events v4.0 and retrospectively verified for women with Stage IB-IVA
      cervix cancer treated consecutively with MRI-guided brachytherapy between 2008
      and 2013. The minimum equivalent dose in 2 Gy fractions delivered to 0.1, 1, 2,
      5, and 10 cm3 of the rectum and bladder and the absolute volume of the rectum
      receiving 55, 60, 65, 70, and 75 Gy3 (V55-75) were collected. The association
      between dose-volume parameters and Grade 2+ rectal/bladder toxicity was examined
      using logistic regression. RESULTS: With a median followup of 44 months,
      cumulative incidences of Grade 2+ rectal and bladder toxicity among the 106
      patients were 29% and 15% at 3 years, respectively. All the dose-volume
      parameters were significantly associated with late Grade 2+ rectal and bladder
      toxicity (p < 0.05), except for bladder [Formula: see text] . On multivariable
      logistic regression, both [Formula: see text]  > 70 Gy3 and V55 > 11 cm3 (p <
      0.05) were predictive of late Grade 2+ rectal toxicity, with improved model
      fitting and higher area under the curve compared with the model with [Formula:
      see text]  > 70 Gy3 alone. CONCLUSIONS: In this study, V55 was predictive of late
      Grade 2+ rectal toxicity. Adding V55 to  [Formula: see text] improved prediction
      accuracy.

PMID- 28757405
TI  - Incidence, Morbidity, and Surgical Outcomes of Complex Spinal Inflammatory
      Syndromes in Adults.
AB  - BACKGROUND: Spondylodiscitis is a rare inflammatory syndrome affecting
      intervertebral discs and adjacent vertebral bodies. Without appropriate therapy,
      serious complications, such as secondary spinal epidural abscess (SEA), may
      prolong recovery time. In this study, we compared the main characteristics of our
      cohort of patients with spondylodiscitis with those of patients reported in the
      international literature and analyzed the impact of complications associated with
      spondylodiscitis on clinical outcomes. METHODS: We designed a retrospective study
      based on the database of the National Institute of Clinical Neurosciences,
      Hungary, between 2008 and 2015. We collected 78 patients suffering from primary
      spondylodiscitis or primary spinal epidural abscess. Based on the main clinical
      characteristics of our population (demographic features, initial symptoms,
      concurrent diseases, laboratory findings, microbiological diagnosis, therapy and
      clinical outcome) we constructed a database. Odds ratio (OR) counting was used to
      define the correlation between etiology and stage of recovery. RESULTS: We found
      a mild increase in the incidence of spondylodiscitis compared with international
      standards, and main demographic and clinical characteristics in concordance with
      international trends. Primary, noncomplicated spondylodiscitis had the best
      outcome results (OR, 1.25), and complicated spondylodiscitis had the worst, as
      well as the lowest OR for total recovery (0.6). CONCLUSIONS: The clinical
      characteristics of our study cohort did not differ from the international trends.
      Primary, noncomplicated spondylodiscitis has the highest odds for absolute
      recovery. Secondary spinal epidural abscess exacerbates ongoing spondylodiscitis,
      and thus should be considered a poor prognostic factor for spondylodiscitis.
      Early diagnosis and treatment may prevent serious complications and provide
      better outcomes.

PMID- 28757406
TI  - Subdural Hemorrhage from Cerebral Amyloid Angiopathy-Related Intracerebral
      Hemorrhage: A Risk Factor for Postoperative Hemorrhage.
AB  - OBJECTIVE: Surgical treatment for cerebral amyloid angiopathy (CAA)-related
      intracerebral hemorrhage (ICH) is controversial. A subset of CAA-related ICH with
      associated subdural hemorrhage (SDH) has been reported. This study aimed to
      evaluate clinical results and surgical outcomes of this type of ICH with
      associated SDH. METHODS: Study participants included 98 patients with CAA-related
      ICH who met Boston criteria. Patients were divided into an SDH group and a
      control (no SDH) group. Clinical and neuroimaging features and surgical outcomes
      of the 2 groups were compared. RESULTS: Lobular shape of hematoma was found
      significantly more often in the SDH group (65.7% [23/35]) compared with the
      control group (25.4% [16/63]; P < 0.001). Subarachnoid hemorrhage was found
      significantly more often in the SDH group (34.3% [12/35]) compared with the
      control group (7.9% [5/63]; P = 0.001). The rate of postoperative hemorrhage was
      significantly higher in the SDH group (61.5% [8/13]) than in the control group
      (16.2% [6/37]; P = 0.006). The frequency of occurrence of postoperative
      hemorrhage was significantly higher in the SDH group (13/13) than in the control
      group (6/37; P = 0.017). A good surgical outcome occurred in none (0/12) of the
      patients in the SDH group, whereas a good surgical outcome occurred in 51.9%
      (14/27) of patients in the control group (P = 0.006). CONCLUSIONS: Patients with
      CAA-related ICH with associated SDH more frequently have postoperative hemorrhage
      and have a worse surgical outcome. These findings are useful in choosing
      therapeutic methods and preoperative planning of surgical strategy.

PMID- 28757407
TI  - Interpregnancy Interval and Congenital Anomalies: A Record-Linkage Study Using
      the Manitoba Population Research Data Repository.
AB  - OBJECTIVE: Congenital anomalies are a serious public health issue, and relatively
      few modifiable risk factors have been identified. Our objective was to
      investigate one such potential risk factor, the interpregnancy interval (IPI).
      METHODS: We conducted a secondary analysis of data housed at the Manitoba Centre
      for Health Policy. In-hospital live births and stillbirths of at least 20 weeks'
      gestation were identified, and consecutive births to the same mother were grouped
      into sibling pairs to calculate the IPI for the younger siblings of each pair.
      Logistic regression models were fit to examine the association between the IPI
      and any congenital anomaly, as well as CNS and chromosomal anomalies, while
      controlling for potentially confounding sociodemographic and clinical factors.
      RESULTS: Among 172 909 live births and stillbirths, the IPI was not significantly
      associated with congenital anomalies overall or with chromosomal anomalies. Short
      IPIs were associated with significantly increased odds of CNS anomalies relative
      to IPIs of 18-23 months (adjusted OR [aOR] for IPIs <6 months 2.15; 95% CI 1.48
      3.12), whereas the aOR for IPIs >=60 months was elevated but not statistically
      significant (aOR 1.50; 95% CI 0.96-2.34). In a sensitivity analysis in which the
      cohort was restricted to births from 2003 onwards (which yielded more complete
      data on health-related behaviours), the observed effect for IPIs shorter than 6
      months and CNS anomalies was attenuated and no longer significant, but it
      remained elevated (aOR 1.65; 95% CI 0.85-3.24). CONCLUSION: The findings for CNS
      anomalies warrant further investigation.

PMID- 28757408
TI  - Molecular Diagnosis of Placental Hydatidiform Mole: Innovation and Outcomes.

PMID- 28757409
TI  - Beyond Plan B: A Qualitative Study of Canadian Pharmacists' Emergency
      Contraception Counselling Practices.
AB  - OBJECTIVE: Pharmacists are often the front-line health care providers for women
      seeking emergency contraception (EC). This study explored Ontario pharmacists' EC
      counselling practices and their perceived barriers to recommending the most
      effective EC method, the copper IUD (Cu-IUD). METHODS: This qualitative study
      used one-on-one, semistructured interviews with 20 pharmacists working in
      pharmacies located within a 1-km radius of a large sexual health clinic that
      offered postcoital IUDs in downtown Toronto. RESULTS: All pharmacists provided
      counselling about levonorgestrel (LNG-EC), and all considered it important.
      Nevertheless, they rarely discussed the Cu-IUD, even in circumstances where LNG
      EC could be less effective, such as delayed presentation or for women with BMI
      >25 kg/m2. Some pharmacists felt conflicted in their dual roles as health care
      and customer service provider when counselling about and selling EC, and many
      felt uncomfortable discussing body weight. Pharmacists were not well informed
      about the Cu-IUD. They identified many pharmacist-specific barriers to
      counselling about the Cu-IUD for EC, as well as health systems issues around Cu
      IUD provision and insertion. CONCLUSION: Ontario pharmacists embraced their role
      in EC counselling, yet their discussions rarely included the most effective Cu
      IUD option. Educating and training pharmacists about the Cu-IUD and establishing
      referral pathways for IUD insertion could expand their counselling about this EC
      option.

PMID- 28757410
TI  - Massive Vaginal Hematoma - A Complication of In Vitro Fertilization.
AB  - BACKGROUND: The rates of serious complications from IVF with transvaginal oocyte
      retrieval are low. However, as the usage of IVF continues to increase, more
      complications are presenting to acute care and physicians should be aware of
      management issues. CASE: A 36-year-old, gravida 4, para 1 woman presented to the
      emergency department with significant vaginal hemorrhage and severe abdominal
      pain after undergoing a routine transvaginal oocyte retrieval. She was taken to
      the operating room and found to have extensive lacerations of the posterior
      vaginal mucosa and a large vaginal hematoma tracking to the retroperitoneal
      space. CONCLUSION: This case represents a previously unreported but possible
      complication of oocyte retrieval. Although oocyte retrieval complications are not
      frequently reported, significant vaginal and pelvic vascular injury and
      hemorrhage can occur. Physicians should be cognizant of trauma that can occur
      secondary to vaginal instruments and not just intraperitoneal injuries.

PMID- 28757411
TI  - Increased ophthalmic acid production is supported by amino acid catabolism under
      fasting conditions in mice.
AB  - Glutathione (GSH) plays pivotal roles in antioxidation and detoxification. The
      transsulfuration pathway, in conjunction with methionine metabolism, produces
      equimolar amounts of cysteine (Cys) and 2-oxobutyric acid (2OB). The resulting
      2OB is then converted into 2-aminobutyric acid (2AB) by a transaminase and is
      utilized as a substitute for Cys by the GSH-synthesizing machinery to produce
      ophthalmic acid (OPT). By establishing a method for simultaneously measuring Cys,
      GSH, and OPT by liquid chromatography-mass spectrometry, we found that fasting
      causes an elevation in OPT levels in the liver and blood plasma, even though the
      levels of Cys and GSH are decreased. Autophagy was activated, but the levels of
      GSH/OPT-synthesizing enzymes remained unchanged. After 6 h of fasting, the mice
      were given 1% 2AB and/or 5% glucose in the drinking water for an additional 24 h
      and the above metabolites analyzed. 2AB administration caused an increase in OPT
      levels, and, when glucose was co-administered with 2AB, the levels of OPT were
      elevated further but GSH levels were decreased somewhat. These results suggest
      that, while Cys is utilized for glyconeogenesis under fasting conditions,
      reaching levels that were insufficient for the synthesis of GSH, 2OB was
      preferentially converted to 2AB via amino acid catabolism and was utilized as a
      building block for OPT. Thus the consumption of Cys and the parallel elevation of
      2AB under fasting conditions appeared to force gamma-glutamylcysteine synthetase
      to form gamma-glutamyl-2AB, despite the fact that the enzyme has a higher Km
      value for 2AB than Cys.

PMID- 28757412
TI  - Quercetin ameliorates learning and memory via the Nrf2-ARE signaling pathway in d
      galactose-induced neurotoxicity in mice.
AB  - Aging is accompanied by deficits in cognitive function and neuronal degeneration
      or loss. Quercetin is a flavonoid that exhibits powerful antioxidant activity.
      This study evaluated the protective effects and mechanisms of quercetin in d
      galactose-induced neurotoxicity in mice. Quercetin was administered daily at
      doses of 20 or 50 mg/kg in d-galactose-injected (50 mg/kg/subcutaneous (s.c.))
      mice for eight weeks. Morris water maze tests demonstrated that quercetin
      significantly improved learning and memory compared to d-galactose-treated
      control mice. Quercetin also prevented changes in the neuronal cell morphology
      and apoptosis in the hippocampus as well as increased the expression of Nrf2, HO
      1 and SOD in d-galactose-treated mice. Treatment with the Nrf2 inhibitor Brusatol
      reversed the effects of quercetin on HO-1 and SOD expression as well as neuronal
      cell protection. In conclusion, quercetin protected mice from d-galactose-induced
      cognitive functional impairment and neuronal cell apoptosis via activation of the
      Nrf2-ARE signaling pathway.

PMID- 28757413
TI  - Restoration of miR-30a expression inhibits growth, tumorigenicity of
      medulloblastoma cells accompanied by autophagy inhibition.
AB  - Medulloblastoma is a highly malignant pediatric brain tumor. About 30% patients
      have metastasis at diagnosis and respond poorly to treatment. Those that survive,
      suffer long term neurocognitive, endocrine and developmental defects due to the
      cytotoxic treatment to developing child brain. It is therefore necessary to
      develop targeted treatment strategies based on underlying biology for effective
      treatment of medulloblastoma with minimal side effects. Medulloblastomas are
      believed to be the result of deregulated nervous system development as evident
      from the role of WNT and SHH developmental signaling pathways in pathogenesis of
      medulloblastomas. MicroRNAs are known to play vital roles in nervous system
      development as well as in cancer. MicroRNA profiling of medulloblastomas
      identified miR-30 family members' expression to be downregulated in
      medulloblastomas belonging to the four known molecular subgroups viz. WNT, SHH,
      Group 3 and Group 4 as compared to that in normal brain tissues. Furthermore,
      established medulloblastoma cell lines Daoy, D283 and D425 were also found to
      underexpress miR-30a. Restoration of miR-30a expression using inducible
      lentiviral vector inhibited proliferation, clonogenic potential and
      tumorigenicity of medulloblastoma cells. MiR-30a is known to target Beclin1, a
      mediator of autophagy. MiR-30a expression was found to downregulate Beclin1
      expression and inhibit autophagy in the medulloblastoma cell lines as judged by
      downregulation of LC3B expression and its turnover upon chloroquine treatment and
      starvation induced autophagy induction. MiR-30a therefore could serve as a novel
      therapeutic agent for the effective treatment of medulloblastoma by inhibiting
      autophagy that is known to play important role in cancer cell growth, survival
      and malignant behavior.

PMID- 28757414
TI  - The wheat salinity-induced R2R3-MYB transcription factor TaSIM confers salt
      stress tolerance in Arabidopsis thaliana.
AB  - MYB transcription factors are a large family of proteins involved in plant
      development and responses to stress. In this study, the wheat salinity-induced
      R2R3-MYB transcription factor TaSIM was functionally characterized, with a focus
      on its role in salt stress tolerance. TaSIM protein enters the nucleus and binds
      to the MYB-binding site II motif. Expression analysis revealed that TaSIM was
      induced by drought, high salinity, low temperature, and abscisic acid treatment.
      Overexpression of TaSIM improved salt stress tolerance in transgenic plants.
      Furthermore, the transcript levels of genes involved in abscisic acid (ABA)
      dependent (RD22) and ABA-independent (RD29A) signaling were higher in TaSIM
      overexpressing plants than in the wild type. These results suggest that TaSIM
      positively modulates salt stress tolerance and has potential applications in
      molecular breeding to enhance salt tolerance in crops.

PMID- 28757415
TI  - Study of the interactions between Edaglitazone and Ciglitazone with PPARgamma and
      their antiplatelet profile.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      activated transcription factor with an important role in lipid metabolism,
      inflammation and cardiovascular diseases. PPARgamma ligands have inhibitory
      effects on platelet aggregation via the cAMP pathway, which may confer them a
      protective cardioprotective role. Edaglitazone and Ciglitazone are two chemically
      similar thiazolidinedione (TZD) drugs that have been described as potent
      PPARgamma agonists; however, Edaglitazone is over 100 times more potent than
      Ciglitazone. Here, we report a computational study to describe the ligand binding
      and the experimental antiplatelet profiles of Edaglitazone and Ciglitazone. Both
      ligands presented similar orientations within the PPARgamma binding site. Their
      polar heads exhibit complex hydrogen bond networks with the residues at arm I
      pocket, while their hydrophobic tails are oriented inside arm II or the entrance
      pocket. The bulkier and longer tail of Edaglitazone exhibited additional
      hydrophobic interactions, explaining its stronger binding to PPARgamma supported
      by binding affinity calculations. On the other hand, both Edaglitazone and
      Ciglitazone displayed an antiplatelet activity, but only Edaglitazone retained
      such effect at low concentrations. Furthermore, we evidenced that Edaglitazone
      increases intraplatelet cAMP levels and prevents PPARgamma secretion, explaining
      its greater antiplatelet activity. Altogether, the more potent PPARgamma agonist
      Edaglitazone seems to be a potent antiplatelet agent.

PMID- 28757416
TI  - The tumour suppressor, miR-137, inhibits malignant melanoma migration by
      targetting the TBX3 transcription factor.
AB  - The transcription factor, TBX3, is a key driver of malignant melanoma and any
      drug that impacts its expression is likely to have an impact on the treatment of
      this highly aggressive and treatment resistant cancer. Replacement of miRNAs that
      target oncogenes has gained much attention as a therapy because it is anticipated
      to be effective with little side-effects since miRNAs are naturally occurring and
      often target large set of genes in the same oncogenic pathway. Here we show that
      miR-137 levels correlate inversely with TBX3 mRNA levels in a panel of melanoma
      cell lines and in a cohort of patients with primary melanoma. Low levels of miR
      137 and high levels of TBX3 are shown to be associated with poor patient
      survival. We show that miR-137 binds a conserved site in the TBX3 3' untranslated
      region and that a miR-137 mimic significantly reduces endogenous levels of TBX3
      and inhibits anchorage independent growth and migration of malignant melanoma
      cells. Novel data are provided that the miR-137/TBX3/E-cadherin axis plays an
      important role in melanomagenesis and that miR-137 replacement is a potential
      therapeutic approach for treating melanomas.

PMID- 28757417
TI  - miRNAs in B-cell lymphoma: Molecular mechanisms and biomarker potential.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate many human genes
      including those involved in normal B-cell development. When these miRNAs are
      aberrantly expressed in B-cells they play key pathogenetic roles in the
      development and maintenance of B-cell lymphomas and by association may serve as
      useful biomarkers. In this review, we provide an overview of the importance of
      miRNAs to B-cell lymphomagenesis, as well as considering their use as biomarkers,
      and their potential usefulness for the clinic.

PMID- 28757418
TI  - Obesity Paradox in Lung Cancer Prognosis: Evolving Biological Insights and
      Clinical Implications.
AB  - The survival rate of lung cancer remains low despite the progress of surgery and
      chemotherapy. With the increasing comorbidity of obesity in patients with lung
      cancer, new challenges are emerging in the management of this patient population.
      A key issue of interest is the prognostic effect of obesity on surgical and
      chemotherapeutic outcomes in patients with lung cancer, which is fueled by the
      growing observation of survival benefits in overweight or obese patients. This
      unexpected inverse relationship between obesity and lung cancer mortality, called
      the obesity paradox, remains poorly understood. The evolving insights into the
      heterogeneity of obesity phenotypes and associated biological connections with
      lung cancer progression in recent years may help explain some of the seemingly
      paradoxical relationship, and well-designed clinical studies looking at the
      causal role of obesity-associated molecules are expected. Here, we examine
      potential biological mechanisms behind the protective effects of obesity in lung
      cancer. We highlight the need to clarify the clinical implications of this
      relationship toward an updated intervention strategy in the clinical care of
      patients with lung cancer and obesity.

PMID- 28757419
TI  - Insights into physicochemical and functional properties of polysaccharides
      sequentially extracted from onion (Allium cepa L.).
AB  - Onion polysaccharides (ACLP) were sequentially extracted with four different
      solvents (hot buffer, chelating agent, dilute alkaline and concentrated alkaline)
      and obtained four fractions, named as HBSS, CHSS, DASS and CASS, respectively.
      The present studies characterized the ACLP concerning its physicochemical and
      functional properties. Monosaccharides analysis revealed that mannose (81.68%)
      was the dominant sugar in HBSS and galactose (67.59%) was the most in CASS.
      Similarly, CHSS and DASS possessed mannose and galactose as major sugar, which
      were 25.80% and 31.37%, 20.33% and 33.96%, respectively. The obtained molecular
      weight of ACLPs were 7.702*103 (HBSS), 4.690*103 (CHSS), 4.943*103 (DASS) and
      1.390*103kDa (CASS). CASS resulted in the strongest solubility, fat-binding
      capacity, foam capacity and foam stability whereas, HBSS showed the highest
      thermal stability. DASS showed the best hygroscopicity and the best moisture
      retention was obtained by CHSS. Subsequently, the emulsifying activity and
      emulsifying stability were the highest for HBSS and the longest for of CASS,
      respectively. The rheological properties of CHSS exhibited the largest viscosity.
      Our results indicated that all factions could be considered as functional
      polysaccharides according to their respective characteristics, which have vast
      potential in food production.

PMID- 28757420
TI  - Effect of different combinations of maltodextrin, gum arabic and whey protein
      concentrate on the encapsulation behavior and oxidative stability of spray dried
      drumstick (Moringa oleifera) oil.
AB  - The objective of the present study was to investigate the effect of different
      combinations of carrier agents (Maltodextrin, gum arabic and whey protein
      concentrate) on the emulsion properties, encapsulation efficiency and oxidative
      stability of encapsulated drumstick oil powder (EDOP), produced by spray drying
      to increase its usage as an active ingredient. Feed emulsion characteristics were
      studied in terms of emulsion stability, droplet size, viscosity and surface
      charge. Obtained spray dried EDOP was characterized for physical and flow
      properties, microstructure and oxidative stability. EDOP obtained from the MD:GA
      emulsion showed higher encapsulation efficiency than MD:WPC. Higher encapsulation
      efficiency along with medium flow properties and better oxidative stability was
      observed with microcapsules obtained by MD:GA carrier agent. Microstructure of
      EDOP with MD:GA showed no cracks, smother appearance with continuous wall. EDOP
      with MD:GA had better stability and were stable at 45 degrees C, which confirms
      the protective effect of this carrier agent in encapsulating the drumstick oil.

PMID- 28757421
TI  - Selective sorption of Fe(II) ions over Cu(II) and Cr(VI) ions by cross-linked
      graft copolymers of chitosan with acrylic acid and binary vinyl monomer mixtures.
AB  - Low-cost and environment-friendly polymeric adsorbents for sorption of heavy
      metal ions were synthesized by simultaneous graft copolymerization and cross
      linking of acrylic acid alone and with comonomers glycidyl methacrylate,
      acrylamide and acrylonitrile onto chitosan using free radical initiator and cross
      linker in aqueous medium. Structural aspects of cross-linked graft copolymers
      have been characterized by FTIR, SEM, TGA/DTA, XRD and swelling behavior at pH
      2.2, 7.0 and 9.4. An attempt has been made to study sorption of Cr(VI), Cu(II)
      and Fe(II) ions on cross-linked graft copolymers by equilibration method and to
      establish a relationship between structural aspects of graft copolymers and metal
      ion uptake efficiency and selectivity. Solutions of individual ions were used for
      non-competitive sorption onto synthesized bio-adsorbents as a function of change
      in contact time, temperature, pH and metal ion concentration in feed. Competitive
      sorption investigation was performed from an aqueous solution of ternary metal
      ions by batch equilibration at 25 degrees C and at 7.0pH. Cross-linked graft
      copolymers showed better results than unmodified chitosan and showed preferential
      sorption of Fe(II) ions than Cu(II) and Cr(VI) ions.

PMID- 28757422
TI  - Combined antibacterial/tissue regeneration response in thermal burns promoted by
      functional chitosan/silver nanocomposites.
AB  - We report the combined antibacterial/tissue regeneration responses to thermal
      burns promoted by functional chitosan/silver nanocomposites (CS/nAg) with
      ultralow silver content (0.018wt.%, 7-30nm). Our approach allows one to produce
      CS/nAg nanocomposites without silver nanoparticles (nAg) agglomeration, with
      bactericide potency higher than 1wt.% of nAg (ca. 10nm) content and, promoting
      the healing process in controlled thermal burns. CS/nAg films exhibit high
      antibacterial activity against S. aureus and P. aeruginosa after 1.5h of
      incubation, demonstrating the bacterial penetration into hydrated films and their
      interaction with nAg. Additionally, exceptional healing of induced thermal burns
      was obtained by increasing myofibroblasts, collagen remodeling, and blood vessel
      neoformation. These factors are associated with epiderma regeneration after 7days
      of treatment with no nAg release. Our results corroborate the controlled
      synthesis of nAg embedded in CS matrix with combined
      antibacterial/biocompatibility properties aiming to produce functional
      nanocomposites with potential use in wound dressing and health care applications.

PMID- 28757423
TI  - Solid-solid crosslinking of carboxymethyl cellulose nanolayer on titanium oxide
      nanoparticles as a novel biocomposite for efficient removal of toxic heavy metals
      from water.
AB  - Nano titanium oxide (Nano-TiO2) was used in this work as a solid support to solid
      solid immobilize carboxymethyl cellulose via glutaraldehyde as an efficient cross
      linking reagent to produce a novel nanosized biocomposite (Nano-TiO2-glu-CMC).
      The synthesized materials were characterized by FT-IR to confirm crosslinking
      reaction between the two species as well as by HR-TEM, SEM, TGA and surface area
      analysis. The particle size was found to correspond to 22.2-44.4nm for Nano-TiO2
      glu-CMC. The designed nanosized biocomposite was used and compared with Nano-TiO2
      for separation and extraction of heavy metal ions such as Cd(II), Pb(II) and
      Hg(II) from aqueous solution by using batch experiment and microcolumn technique.
      The maximum metal sorption capacity values of Cd(II), Pb(II) and Hg(II) were
      established as 2440MUmolg-1 (pH 7), 2880MUmolg-1 (pH 6) and 1160MUmolg-1 (pH 3),
      respectively. Optimization of the extraction experiments confirmed the maximum
      adsorption upon using 0.025g biocomposite dosage and 30min contact time.

PMID- 28757424
TI  - Evaluation of chemical modified hydrogel formulation for topical suitability.
AB  - BACKGROUND: Skin delivery and transdermal delivery are key ambitions of the
      pharmaceutical and cosmetically researchers. AIM: The study aimed to chemically
      modify well-known polymeric gelling agents in order to boost their topical
      suitability by fostering their dermal adhesiveness. METHODS: Conventional
      chitosan was modified via amide bound formation with sulfhydryl compound
      thioglycolic acid. Subsequently, preactivated chitosan conjugate was established
      by preactivation of chitosan-thioglycolic acid with mercaptonicotinamide being
      covalently attached via disulfide bond linkage. All conjugates were examined due
      to their dermal adhesiveness and controlled drug release properties. RESULTS:
      Preactivated chitosan conjugates Exhibit 7.46-fold dermal adhesiveness on skin
      due to tensile adhesion strength. Furthermore a 1.9-fold controlled release of
      Rhodamine123 as model drug was determined in comparison to unmodified chitosan.
      CONCLUSION: Taken together, preactivated chitosan gels show a promising platform
      for topical application.

PMID- 28757425
TI  - Modification of xanthan solution properties by the cationic surfactant DTMAB.
AB  - The interactions between xanthan gum (XG) and dodecyltrimethylammonium bromide
      (DTMAB) are studied by static and dynamic light scattering, microrheology and
      viscometry within the overlapping regime of aqueous xanthan solutions. In the
      absence of salt mixing with surfactant transforms the complex fluid of
      interconnected xanthan chains into diffusing aggregates because of the reduction
      of the polysaccharide's effective charge and the introduction of hydrophobic
      units. In the presence of salt the effect of complexation is weaker. Mixing the
      two components while XG is in its denatured state results to a network with
      reduced interchain connections. Linear (microrheological) and nonlinear (steady
      shear) viscoelastic experiments show that there is a significant compromise of
      the viscoelastic moduli which is remarkably more intense when mixing DTMAB with
      XG in its denatured state. These findings prove that xanthan's viscoelastic and
      morphological properties may be tuned by addition of surfactants and that the
      conformational state of XG during complexation is a defining parameter.

PMID- 28757426
TI  - Emerging role of Interleukins IL-23/IL-17 axis and biochemical markers in the
      pathogenesis of Type 2 Diabetes: Association with age and gender in human
      subjects.
AB  - Chronic hyperglycaemia in type 2 diabetes (T2D) is associated with increased
      oxidative stress and inflammation. Keeping the above fact into consideration we
      analyse the effect of age and gender on oxidative stress biomarkers and pro
      inflammatory cytokines in T2D patients. The study included 148 diabetic and 110
      healthy subjects, grouped on the basis of age and gender. Plasma malondialdehyde,
      protein carbonyl content and nitric oxide levels were elevated significantly in
      diabetic patients, with significant decrease in Ferric reducing ability of
      plasma, vitamin C, reduced glutathione, erythrocyte thiol groups and erythrocyte
      antioxidant enzyme activity and these changes were even more pronounced as age
      progressed. Serum IL-1beta, IL-6, IL-17A, IL-22 levels and TNF-alpha mRNA
      expression was significantly upregulated in all the age groups whereas IL-23 mRNA
      was upregulated only in the higher age group. Female diabetic patients
      experienced higher oxidative stress and greater serum IL-6 levels and TNF-alpha
      mRNA expression as compared to their male counterparts. This study suggested that
      diabetes onset is accompanied with increased oxidative stress and elevated levels
      of inflammatory mediators. The effect was more prominent in aged patients. Female
      patients experienced greater oxidative stress as compared to males of those age
      groups with slightly higher levels of inflammatory cytokines.

PMID- 28757427
TI  - A debranching enzyme IsoM of Corallococcus sp. strain EGB with potential in
      starch processing.
AB  - Interest in use of resistant starch and maltooligosaccharides as functional foods
      and biopreservatives has grown in recent years. In this research, a novel
      debranching enzyme IsoM from Corallococcus sp. strain EGB was identified and
      expressed in P. pastoris GS115. Sequence alignments showed that IsoM was typical
      isoamylase with the specific activity up to 70,600U/mg, which belongs to
      glycoside hydrolase family 13 (GH 13). Enzymatic reaction pattern demonstrated
      that IsoM has high debranching efficiency against alpha-1,6-glycosidic bond of
      branched starch, and exhibited no activity towards alpha-1,4-glycosidic bond. The
      potential application of IsoM in starch processing was determined. IsoM was a
      potential candidate for the production of RS (70.9%) from raw starch, which was
      comparable with the commercial pullulanase (Promozyme(r)D2). IsoM also improved
      the maltohexaose yield in combination with maltohexaose-producing alpha-amylase
      AmyM (KM114206), the maltohexaose yield was improved by 63.3% compared with 21.9%
      improvement of Promozyme(r)D2. The results of RS production and combination with
      other amylases suggesting that IsoM is a potential candidate for the efficient
      conversion of starch.

PMID- 28757428
TI  - Augmented osteoplasty for proximal femur consolidation in cancer patients:
      Biomechanical considerations and techniques.
AB  - According to the literature, prophylactic consolidation of lytic metastasis
      located in the proximal femur is recommended when the Mirels' score is above 8.
      Osteoplasty alone provides inadequate consolidation but various devices have been
      used in association for better consolidation. The aim of this review is to detail
      the augmented osteoplasty techniques published in the literature and to report
      their safeties and their efficacies to prevent pathological fracture of the
      proximal femur. A Pubmed research found 5 studies that evaluated augmented
      osteoplasty of the proximal femur in cancer patients. All devices demonstrate
      adequate safety and low rate of secondary pathological fractures.

PMID- 28757429
TI  - Women's career choices in radiology in France.
AB  - PURPOSE: The purpose of this study was to determine the possible effects of
      gender on residents' and fellows' motivations in choosing radiology as a career
      in France, and on choosing a practice setting later on. MATERIAL AND METHODS: An
      online survey was sent to French residents and fellows in order to access their
      radiology practice and career aspirations, as well as the potential influence of
      their gender. Influence of being a woman on initial professional expectations,
      professional choices, and the evolution of career paths was investigated using
      the chi-square test. RESULTS: Responses were collected from 206 French residents
      and fellows. The reasons for choosing radiology residency were, at first, mostly
      the same for men and women such as interest in the specialty (100% of women and
      men), work conditions (74% of women and men), technical aspects of the specialty
      (63% of men and 52% of women, P=0.11) or "reasonable" workload (29% women and 21%
      men, P=0.19); however, 74% of women stated that maternity might influence their
      career choices, and were less interested in unstable positions exclusively in
      private practice (45% men and 33% women, P=0.05). CONCLUSION: Male and female
      radiologists primarily considered the same factors in choosing their specialties.
      However, maternity is still a source of inequality in France, including fewer
      opportunities for fellowship positions or academic careers. Furthermore, more
      women were willing to work in salaried positions to acquire a secure job, even
      though compensation might be lower.

PMID- 28757430
TI  - Resuscitation outcomes of cardiac arrest patients who caused witnessed non-fatal
      road traffic accidents while driving.

PMID- 28757431
TI  - Perforin-A key (shaped) weapon in the immunological arsenal.
AB  - Cytotoxic lymphocytes play a key role in immune homeostasis through elimination
      of virally-infected and transformed target cells. They do this by employing the
      potent pore-forming protein, perforin, a molecule that permits cytotoxic
      proteases, such as granzyme B, to enter the target cell cytoplasm. The
      synergistic activities of perforin and granzymes bring about the destruction of
      target cells in a process that is now more clearly understood as a result of
      structural and cellular biology. These data are helping the development of new
      classes of immunosuppressive molecules for use in treating immune driven disease
      and in enhancing the success of transplant therapies. This review focuses on
      structural and biological aspects of perforin function.

PMID- 28757432
TI  - Genetic risk of prediabetes and diabetes development in chronic myeloid leukemia
      patients treated with nilotinib.
AB  - Impaired fasting glucose and type 2 diabetes represent adverse events in patients
      with chronic myeloid leukemia (CML) treated with the second generation tyrosine
      kinase inhibitor nilotinib. An unweighted genetic risk score (uGRS) for the
      prediction of insulin resistance, consisting of 10 multiple single-nucleotide
      polymorphisms, has been proposed. We evaluated uGRS predictivity in 61 CML
      patients treated with nilotinib. Patients were genotyped for IRS1, GRB14, ARL15,
      PPARG, PEPD, ANKRD55/MAP3K1, PDGFC, LYPLAL1, RSPO3, and FAM13A1 genes. The uGRS
      was based on the sum of the risk alleles within the set of selected single
      nucleotide polymorphisms. Molecular response (MR)3.0 and MR4.0 were achieved in
      90% and 79% of patients, respectively. Before treatment, none of the patients had
      abnormal blood glucose. During treatment and subsequent follow-up at 80.2 months
      (range: 1-298), seven patients (11.5%) had developed diabetes that required oral
      treatment, a median of 14 months (range: 3-98) after starting nilotinib
      treatment. Twelve patients (19.7%) had developed prediabetes.
      Prediabetes/diabetes-free survival was significantly higher in patients with a
      uGRS <10 than in those with higher scores (100% vs. 22.8 +/- 12.4%, p <0.001).
      Each increment of one unit in the uGRS caused a 42% increase in the
      prediabetes/diabetes risk (hazard ratio = 1.42, confidence interval: 1.04-1.94, p
      = 0.026). The presence of more than 10 allelic variants associated with insulin
      secretion, processing, sensitivity, and clearance is predictive of
      prediabetes/diabetes development in CML patients treated with nilotinib. In
      clinical practice, uGRS could help tailor the best tyrosine kinase inhibitor
      therapy.

PMID- 28757434
TI  - Adrenal responses of large whales: Integrating fecal aldosterone as a
      complementary biomarker to glucocorticoids.
AB  - Until now, physiological stress assessment of large whales has predominantly
      focused on adrenal glucocorticoid (GC) measures. Elevated GC concentrations in
      feces (fGC) are known to reflect stressful disturbances, such as fishing gear
      entanglement and human-generated underwater noise, in North Atlantic right whales
      (Eubalaena glacialis). However, there can be considerable variation in GC
      production as a function of sex and life history stage, which may confound the
      interpretation of fGC levels. Additionally, GC antibodies used in immunoassays
      can cross-react with other fecal metabolites (i.e., non-target steroids),
      potentially influencing fGC data. Here, aldosterone concentrations (fALD;
      aldosterone and related metabolites) were measured in fecal samples from right
      whales (total n=315 samples), including samples from identified individuals of
      known life history (n=82 individual whales), to evaluate its utility as a
      complementary biomarker to fGC for identifying adrenal activation. Concentrations
      of fALD were positively correlated with fGCs in right whales (r=0.59, P<0.001),
      suggesting concurrent secretion of these hormones by the adrenal gland. However,
      fALD levels were less influenced by concentrations of reproductive steroids in
      feces, minimizing the potential confounder of assay cross-reactivity in samples
      with highly skewed hormone ratios. Across different life history states for right
      whales, fALD concentrations showed similar patterns to those reported for fGC,
      with higher levels in pregnant females (35.9+/-7.6ng/g) followed by
      reproductively mature males (9.5+/-0.9ng/g) (P<0.05), providing further evidence
      of elevated adrenal activation in these groups of whales. The addition of fALD
      measurement as a biomarker of adrenal activation may help distinguish between
      intrinsic and external causes of stress hormone elevations in large whales, as
      well as other free-living wildlife species, providing a more comprehensive
      approach for associating adrenal activation with specific natural and
      anthropogenic stressors.

PMID- 28757433
TI  - Technical considerations for the use of CRISPR/Cas9 in hematology research.
AB  - The hematopoietic system is responsible for transporting oxygen and nutrients,
      fighting infections, and repairing tissue damage. Hematopoietic system
      dysfunction therefore causes a range of serious health consequences. Lifelong
      hematopoiesis is maintained by repopulating multipotent hematopoietic stem cells
      (HSCs) that replenish shorter-lived, mature blood cell types. A prokaryotic
      mechanism of immunity, the Clustered Regularly Interspaced Short Palindromic
      Repeats (CRISPR)/Cas9 nuclease system, has been recently "repurposed" to mutate
      mammalian genomes efficiently and in a sequence-specific manner. The application
      of this genome-editing technology to hematology has afforded new approaches for
      functional genomics and even the prospect of "correcting" dysfunctional HSCs in
      the treatment of serious genetic hematological diseases. In this Perspective, we
      provide an overview of three recent CRISPR/Cas9 methods in hematology: gene
      disruption, gene targeting, and saturating mutagenesis. We also summarize the
      technical considerations and advice provided during the May 2017 International
      Society of Experimental Hematology New Investigator Committee webinar on the same
      topic.

PMID- 28757435
TI  - TEMPORARY REMOVAL: North American Forum on Family Planning, Scientific Abstracts,
      Atlanta, Georgia, October 14-16, 2017.
AB  - The publisher regrets that this article has been temporarily removed. A
      replacement will appear as soon as possible in which the reason for the removal
      of the article will be specified, or the article will be reinstated. The full
      Elsevier Policy on Article Withdrawal can be found at
      https://www.elsevier.com/about/our-business/policies/article-withdrawal.

PMID- 28757436
TI  - Etanercept and Corticosteroid Therapy for the Treatment of Late-Onset Idiopathic
      Pneumonia Syndrome.
AB  - Idiopathic pneumonia syndrome (IPS) is a complication of allogeneic hematopoietic
      stem cell transplantation (HSCT) that typically occurs within the first 100 days
      after transplantation. Tumor necrosis factor alpha (TNF-alpha) has been shown to
      be a key mediator of IPS, and the TNF-alpha binding protein etanercept appeared
      to improve IPS outcomes in small retrospective and prospective studies. IPS also
      has been observed to occur later (>100 days) after HSCT; however, little is known
      about the disease course and whether a TNF-alpha-based therapeutic strategy is
      efficacious in these patients. To address this question, we performed a
      retrospective analysis of 23 patients who underwent HSCT between 2004 and 2016 at
      our institution who developed late-onset IPS and received treatment with
      etanercept and high-dose corticosteroids (CS). Ten of the 23 patients (43%)
      attained a complete clinical response to etanercept and CS. Responses were
      significantly more likely to occur in patients who did not require positive
      pressure ventilation at the time of diagnosis. Those who responded experienced a
      durable survival benefit, with a 2-year overall survival of 67%. In the 13
      patients (57%) who did not respond to etanercept and CS, the median overall
      survival was only 13 days (range, 1 to 60 days). The difference in 2-year overall
      survival between responders and nonresponders was statistically significant (67%
      versus 0%; P < .001). These results indicate that late-onset IPS carries high
      mortality, but that treatment with etanercept and CS has activity and can result
      in long-term survival in some patients. Prompt diagnosis and early institution of
      therapy before the need for advanced respiratory support is critical for
      maximizing responses.

PMID- 28757437
TI  - Family food and shape messages: Capturing the experiences of African-American
      women.
AB  - Four studies explored the family food experiences (FFEs) of African-American (AA)
      in relation to disordered eating and body image concerns. Focus groups of AA
      women expressed FFEs that shaped their relationships with food (Study 1). We used
      the resulting framework to create a measure assessing FFEs related to disordered
      eating (Family Food Experiences-Black Questionnaire; FFBQ). Measure items were
      subjected to a content analysis (Study 2). Subject matter experts rated ten items
      essential (CVR >= 0.62, p < 0.05). An exploratory factor analysis (EFA) was
      performed on the 10-item FFBQ in a sample of AA (N = 66) women (Study 3). The two
      factor model explained 41.14% of the variance in the items (Chi2 = 25.04, df =
      26, p = 0.52. Finally, a confirmatory factor analysis (CFA) was performed on the
      FFBQ in a new sample of AA women (N = 167) to confirm the factor structure. The
      EFA yielded two subscales: a Traditional Thin-Ideal (TTI) and a Curvy Ideal (CI)
      subscale (reflecting messages that emphasize valuation of curves). These
      subscales were confirmed by CFA in a second sample of AA women with modifications
      to two items (Chi2 = 32.63, Chi2/df = 2.04). Disordered eating was positively
      correlated with messages reflecting both ideals while only messages reflecting
      the Curvy Ideal was related to body image disturbance. Implications include a
      need for further study of the duality of body ideal messages and the impact on
      body image/disordered eating disturbance in AA women.

PMID- 28757438
TI  - Does the Difference in Fascial Closure Technique Affect Postoperative Pain?
AB  - STUDY OBJECTIVE: To compare postoperative incisional pain on postoperative days
      (PODs) 1 and 14 when using a fascial closure device (FCD) versus a traditional
      fascial closure (TFC) of the 12-mm upper quadrant port during robotic surgery.
      Time required to close the incision was also compared. DESIGN: Randomized
      controlled trial (Canadian Task Force classification I). SETTING: Two academic
      affiliated hospitals, The Hospital of Central Connecticut and The University of
      Connecticut. PATIENTS: Women undergoing robotic surgery for benign indications by
      minimally invasive gynecologists at our institutions between November 2012 and
      October 2014 were enrolled in the study at their preoperative visit.
      INTERVENTIONS: Patients were randomized to either an FCD or TFC immediately
      before closure of the fascial incision. Pain score using a 10-point analog pain
      scale was recorded on POD 1 and POD 14. Time to close the fascial incision,
      length of surgery, and body mass index were also recorded. MEASUREMENTS AND MAIN
      RESULTS: Sixty-seven patients were enrolled, and 65 were randomized at the time
      of the fascial closure, whereas 2 enrolled patients converted to laparotomy.
      Statistical analysis demonstrated that pain scores differed by fascial closure
      technique. Mean pain scores on POD 1 were 3.43 +/- 2.48 and 2.06 +/- 2.03 for the
      FCD and TFC, respectively (p = .028). On POD 14 the mean pain scores were 1.97 +/
      2.48 and .83 +/- 1.42 for the FCD and TFC, respectively (p = .102). Times to
      close fascia were 106.5 +/- 102.28 seconds and 141.97 +/- 102.85 seconds for the
      FCD and TFC, respectively (p = .138). CONCLUSION: Our study demonstrates that at
      POD 1 the use of the fascia closure device results in higher pain scores without
      a significant difference in closure time.

PMID- 28757439
TI  - A Comparison of Robotic Simulation Performance on Basic Virtual Reality Skills:
      Simulator Subjective Versus Objective Assessment Tools.
AB  - STUDY OBJECTIVE: To answer the question of whether there is a difference between
      robotic virtual reality simulator performance assessment and validated human
      reviewers. Current surgical education relies heavily on simulation. Several
      assessment tools are available to the trainee, including the actual robotic
      simulator assessment metrics and the Global Evaluative Assessment of Robotic
      Skills (GEARS) metrics, both of which have been independently validated. GEARS is
      a rating scale through which human evaluators can score trainees' performances on
      6 domains: depth perception, bimanual dexterity, efficiency, force sensitivity,
      autonomy, and robotic control. Each domain is scored on a 5-point Likert scale
      with anchors. We used 2 common robotic simulators, the dV-Trainer (dVT; Mimic
      Technologies Inc., Seattle, WA) and the da Vinci Skills Simulator (dVSS;
      Intuitive Surgical, Sunnyvale, CA), to compare the performance metrics of robotic
      surgical simulators with the GEARS for a basic robotic task on each simulator.
      DESIGN: A prospective single-blinded randomized study. SETTING: A surgical
      education and training center. PARTICIPANTS: Surgeons and surgeons in training.
      INTERVENTIONS: Demographic information was collected including sex, age, level of
      training, specialty, and previous surgical and simulator experience. Subjects
      performed 2 trials of ring and rail 1 (RR1) on each of the 2 simulators (dVSS and
      dVT) after undergoing randomization and warm-up exercises. The second RR1 trial
      simulator performance was recorded, and the deidentified videos were sent to
      human reviewers using GEARS. Eight different simulator assessment metrics were
      identified and paired with a similar performance metric in the GEARS tool. The
      GEARS evaluation scores and simulator assessment scores were paired and a
      Spearman rho calculated for their level of correlation. MEASUREMENTS AND MAIN
      RESULTS: Seventy-four subjects were enrolled in this randomized study with 9
      subjects excluded for missing or incomplete data. There was a strong correlation
      between the GEARS score and the simulator metric score for time to complete
      versus efficiency, time to complete versus total score, economy of motion versus
      depth perception, and overall score versus total score with rho coefficients
      greater than or equal to 0.70; these were significant (p < .0001). Those with
      weak correlation (rho >=0.30) were bimanual dexterity versus economy of motion,
      efficiency versus master workspace range, bimanual dexterity versus master
      workspace range, and robotic control versus instrument collisions. CONCLUSION: On
      basic VR tasks, several simulator metrics are well matched with GEARS scores
      assigned by human reviewers, but others are not. Identifying these
      matches/mismatches can improve the training and assessment process when using
      robotic surgical simulators.

PMID- 28757440
TI  - Nitric oxide synthase inhibition impairs muscle regrowth following
      immobilization.
AB  - : Nitric oxide (NO) has been shown to increase skeletal muscle protein synthesis.
      However, the role of NO during skeletal muscle regrowth after immobilization
      remains unknown. The purpose of this study was to determine whether NO is
      required for muscle regrowth/recovery after a period of disuse by immobilization.
      Male Wistar rats were divided into 4 groups: recovered, 1-(2-trifluoromethyl
      phenyl)-imidazole (TRIM; 10 mg.kg body mass-1.day-1), NG-nitro-l-arginine methyl
      ester (l-NAME; 90 mg.kg body mass-1.day-1), and control. The recovered, TRIM, l
      NAME groups were submitted to a 7-d muscle recovery period (by remobilization),
      following a 10-d immobilization period (to induce plantaris [PLA] muscle
      atrophy). After the experimental period, the PLA muscle was collected for
      morphometrical (muscle fibers cross-sectional area [CSA]) and molecular (Phospho
      mTORSer2448 protein expression) analysis. After 7 d of recovery, the recovered
      group displayed complete muscle regrowth (CSA, recovered: 2.216 +/- 214 vs.
      CONTROL: 2.219 +/- 280 cm2; P > 0.05). However, CSA of the l-NAME (1.911 +/- 267
      cm2) and TRIM (1.896 +/- 219 cm2) groups were statistically (P < 0.05) lower than
      the recovered and control groups. Additionally, there was a 29% increase in Phos
      mTORSer2448 protein expression levels in the recovered group compared to control
      group, and this increase was blocked in both TRIM and l-NAME groups. In
      conclusion, our results indicate that NO is crucial for skeletal muscle regrowth
      after an immobilization period, potentially via the mTOR signaling pathway.

PMID- 28757441
TI  - Exogenous nitric oxide enhances the prophylactic effect of aminoguanidine, a
      preferred iNOS inhibitor, on bleomycin-induced fibrosis in the lung: Implications
      for the direct roles of the NO molecule in vivo.
AB  - OBJECTIVE: Inducible nitric oxide synthase (iNOS) aggravates and endothelial
      nitric oxide synthase (eNOS) ameliorates fibrosis in the lung. Our previous study
      demonstrated that aminoguanidine (AG), a preferred iNOS inhibitor, prevents
      bleomycin-induced injury and fibrosis in the lung. The diethylenetriamine nitric
      oxide adduct (DETA/NO) is a slow-release NO donor. Here, to clarify the exact
      role of the nitric oxide (NO) molecule in the pathogenesis of pulmonary fibrosis
      in vivo, we observed the effects of inhalation of aerosolized DETA/NO on fibrosis
      in the lungs of bleomycin-exposed rats with AG treatment, including the effects
      on the myofibroblast number, collagen deposition, peroxynitrite anion (ONOO-)
      formation, and injury in the lung. DESIGN AND METHODS: Rats received a single
      intratracheal instillation of bleomycin or normal saline (NS) on day 0, followed
      by a daily intraperitoneal injection of AG or NS from day 1 to day 13. Each group
      was additionally given a daily inhalation of DETA/NO or placebo from day 1 to day
      13. On day 14, half of the rats in each group was euthanized, and plasma nitrite
      and nitrate (NOx), myofibroblasts, type I collagen, ONOO- and injury in the lung
      were estimated by the Griess reaction, western blotting, immunohistochemical
      staining, sirius red staining, and hematoxylin and eosin (HE) staining,
      respectively. On day 28, the other half of the rats in each group was euthanized,
      and the total collagen of the lung was evaluated by hydroxyproline assay.
      RESULTS: 1 At the day 14 time point, AG reduced the plasma NOx level in bleomycin
      rats, while this drug had no significant effect on sham rats. Inhalation of
      aerosolized DETA/NO increased the plasma NOx level of bleomycin + AG rats, sham
      rats and sham + AG rats. However, due to large areas of airspace obliteration in
      the lungs of bleomycin rats, DETA/NO inhalation had no significant effect on the
      plasma NOx level in these rats. 2 At the day 14 time point, AG reduced ONOO-
      formation (marked by nitrotyrosine, NT), injury, myofibroblast number, and type I
      collagen deposition in the lungs of bleomycin rats, while this drug had no
      significant impact on the above parameters in the lungs of sham rats.
      Interestingly, DETA/NO inhalation enhanced the preventive effects afforded by AG
      on myofibroblast number and type I collagen deposition, but had no significant
      impact on ONOO- and injury in lung. 3 At the day 28 time point, because rats were
      not exposed to DETA/NO after day 13, there was no significant difference of the
      plasma NOx level in sham rats, sham + AG rats, bleomycin rats, and bleomycin + AG
      rats between DETA/NO inhalation and placebo inhalation. Interestingly, rats
      administered both DETA/NO and AG still showed a reduction in total collagen of
      the entire lung compared to rats administered AG alone at this time point.
      CONCLUSIONS: Exogenous NO enhances the prophylactic effect afforded by AG on the
      myofibroblast number and collagen deposition in the lungs of bleomycin-treated
      rats in vivo. These results suggest that NO has a direct antifibrotic effect in
      lungs, except for the formation of ONOO- in the development of pulmonary fibrosis
      in vivo.

PMID- 28757442
TI  - Endothelin receptor mediated Ca2+ signaling in coronary arteries after
      experimentally induced ischemia/reperfusion injury in rat.
AB  - BACKGROUND: Acute myocardial infarction is one of the leading causes of death. It
      is caused by a blockage of a coronary artery leading to reduced blood flow to the
      myocardium and hence ischemic damage. In addition, a second wave of damage after
      the flow has been restored, named reperfusion injury greatly exacerbate the
      damage. For the latter, no medical treatment exist. In this study the aim was to
      characterize Ca2+ sensitivity in coronary arteries following experimental
      ischemia/reperfusion injury. METHODS: Arteries were isolated from hearts exposed
      to a well-established rat ischemia/reperfusion model. Wire myograph combined with
      FURA2-AM measurements was applied to study the Ca2+ dependency of the
      vasoconstriction. RESULTS: The results presented herein show that ETB receptors
      (R) have much weaker Ca2+-sensitizing effect than ETA-R and that ETB-R appear to
      be more dependent on Ca2+ influx presumably through voltage-gated Ca2+ channels
      (VGCC). In addition, we show that there is an increase in the stretch-induced
      tone after ischemia/reperfusion, and that this increase in tone is independent of
      the ETB-R upregulation. CONCLUSION: Our data support the theory that
      ischemia/reperfusion may induce a phenotypical shift, which includes increased
      evoked ETB induced contraction in the smooth muscle cell, and also a higher basal
      tone development which both are dependent on Ca2+ influx through VGCCs. This is
      combined with alterations in the ETA calcium handling, which has a stronger
      dependence on Ca2+ release from the sarcoplasmic reticulum after I/R injury.

PMID- 28757443
TI  - Synthetic studies of (23S,25R)-1alpha,25-dihydroxyvitamin D3 26,23-lactone
      (calcitriol lactone) and its derivatives.
AB  - (23S,25R)-1alpha,25-Dihydroxyvitamin D3 26,23-lactone (calcitriol lactone) is a
      major metabolite of 1alpha,25-dihydroxyvitamin D3 that binds to vitamin D
      receptor (VDR) and exhibits various biological activities. This lactone and its
      derivatives are considered to have potential as drug candidates to treat VDR
      related diseases, but their biological activities have not yet been fully
      characterized, mainly because of their limited availability by chemical
      synthesis. This review deals with synthetic studies of calcitriol lactone, and
      its derivatives, i.e., methylene lactones (TEI-9647 and its derivatives) and
      calcitriol lactams (DLAMs). We also discuss their biological activities, VDR
      binding affinity and structure-activity relationships.

PMID- 28757444
TI  - Possible role of PAPR-1 in protecting human HaCaT cells against cytotoxicity of
      SiO2 nanoparticles.
AB  - Nano-SiO2 materials play a significant role in the engineered nanomaterials
      (ENMs) field. The ease of their production as well as their relatively low cost
      has promoted the wide use of these products in many fields. Nano-SiO2 exposure is
      known to cause severe DNA damage; however, the underlying mechanisms remain
      poorly understood. In a previous study, we found that nano-SiO2 exposure regulate
      the expression of the poly(ADP-ribose) polymerases-1 (PARP-1), a pivotal DNA
      repair gene, in human HaCaT cells. Here, we employed lentivirus-mediated RNA
      interference (RNAi) to knock down PAPR-1 expression in HaCaT cells and explored
      the potential role of PARP-1 in nano-SiO2 induced cytotoxicity. We found that
      nano-SiO2 treatment of HaCaT cells causes decreased cell viability, increased
      apoptosis and DNA damage. Nano-SiO2-treated HaCaT cells were also found to have
      slightly changed cell cycle distribution. Lentivirus-mediated PAPR-1 knockdown
      partially aggravated cytotoxicity and increased apoptosis induced by nano-SiO2
      treatment. Nano-SiO2 had significant toxicity to human HaCaT cells and causes DNA
      damage. PAPR-1 knock-down cell line appears more sensitive to nano-SiO2 than the
      control cells in DNA damage. The results suggest that PAPR-1 is involved in
      protecting cells from damage caused by nano-SiO2.

PMID- 28757445
TI  - Phylogenetics of Australasian gall flies (Diptera: Fergusoninidae): Evolutionary
      patterns of host-shifting and gall morphology.
AB  - This study investigated host-specificity and phylogenetic relationships in
      Australian galling flies, Fergusonina Malloch (Diptera: Fergusoninidae), in order
      to assess diversity and explore the evolutionary history of host plant
      affiliation and gall morphology. A DNA barcoding approach using COI data from 203
      Fergusonina specimens from 5gall types on 56 host plant species indicated 85
      presumptive fly species. These exhibited a high degree of host specificity; of
      the 40 species with multiple representatives, each fed only on a single host
      genus, 29 (72.5%) were strictly monophagous, and 11 (27.5%) were reared from
      multiple closely related hosts. COI variation within species was not correlated
      with either sample size or geographic distance. However variation was greater
      within oligophagous species, consistent with expectations of the initial stages
      of host-associated divergence during speciation. Phylogenetic analysis using both
      nuclear and mitochondrial genes revealed host genus-restricted clades but also
      clear evidence of multiple colonizations of both host plant genus and host
      species. With the exception of unilocular peagalls, evolution of gall type was
      somewhat constrained, but to a lesser degree than host plant association.
      Unilocular peagalls arose more often than any other gall type, were primarily
      located at the tips of the phylogeny, and did not form clades comprising more
      than a few species. For ecological reasons, species of this gall type are
      predicted to harbor substantially less genetic variation than others, possibly
      reducing evolutionary flexibility resulting in reduced diversification in
      unilocular gallers.

PMID- 28757446
TI  - Playing with extremes: Origins and evolution of exaggerated female forelegs in
      South African Rediviva bees.
AB  - Despite close ecological interactions between plants and their pollinators, only
      some highly specialised pollinators adapt to a specific host plant trait by
      evolving a bizarre morphology. Here we investigated the evolution of extremely
      elongated forelegs in females of the South African bee genus Rediviva
      (Hymenoptera: Melittidae), in which long forelegs are hypothesised to be an
      adaptation for collecting oils from the extended spurs of their Diascia host
      flowers. We first reconstructed the phylogeny of the genus Rediviva using seven
      genes and inferred an origin of Rediviva at around 29MYA (95% HPD=19.2-40.5),
      concurrent with the origin and radiation of the Succulent Karoo flora. The common
      ancestor of Rediviva was inferred to be a short-legged species that did not visit
      Diascia. Interestingly, all our analyses strongly supported at least two
      independent origins of long legs within Rediviva. Leg length was not correlated
      with any variable we tested (ecological specialisation, Diascia visitation,
      geographic distribution, pilosity type) but seems to have evolved very rapidly.
      Overall, our results indicate that foreleg length is an evolutionary highly
      labile, rapidly evolving trait that might enable Rediviva bees to respond quickly
      to changing floral resource availability.

PMID- 28757447
TI  - The phylogeny of extant starfish (Asteroidea: Echinodermata) including Xyloplax,
      based on comparative transcriptomics.
AB  - Multi-locus phylogenetic studies of echinoderms based on Sanger and RNA-seq
      technologies and the fossil record have provided evidence for the Asterozoa
      Echinozoa hypothesis. This hypothesis posits a sister relationship between
      asterozoan classes (Asteroidea and Ophiuroidea) and a similar relationship
      between echinozoan classes (Echinoidea and Holothuroidea). Despite this consensus
      around Asterozoa-Echinozoa, phylogenetic relationships within the class
      Asteroidea (sea stars or starfish) have been controversial for over a century.
      Open questions include relationships within asteroids and the status of the
      enigmatic taxon Xyloplax. Xyloplax is thought by some to represent a newly
      discovered sixth class of echinoderms - and by others to be an asteroid. To
      address these questions, we applied a novel workflow to a large RNA-seq dataset
      that encompassed a broad taxonomic and genomic sample. This study included 15
      species sampled from all extant orders and 13 families, plus four ophiuroid
      species as an outgroup. To expand the taxonomic coverage, the study also
      incorporated five previously published transcriptomes and one previously
      published expressed sequence tags (EST) dataset. We developed and applied methods
      that used a range of alignment parameters with increasing permissiveness in terms
      of gap characters present within an alignment. This procedure facilitated the
      selection of phylogenomic data subsets from large amounts of transcriptome data.
      The results included 19 nested data subsets that ranged from 37 to 4,281loci.
      Tree searches on all data subsets reconstructed Xyloplax as a velatid asteroid
      rather than a new class. This result implies that asteroid morphology remains
      labile well beyond the establishment of the body plan of the group. In the
      phylogenetic tree with the highest average asteroid nodal support several
      monophyletic groups were recovered. In this tree, Forcipulatida and Velatida are
      monophyletic and form a clade that includes Brisingida as sister to
      Forcipulatida. Xyloplax is consistently recovered as sister to Pteraster.
      Paxillosida and Spinulosida are each monophyletic, with Notomyotida as sister to
      the Paxillosida. Valvatida is recovered as paraphyletic. The results from other
      data subsets are largely consistent with these results. Our results support the
      hypothesis that the earliest divergence event among extant asteroids separated
      Velatida and Forcipulatacea from Valvatacea and Spinulosida.

PMID- 28757448
TI  - Is initiating tanning bed use as a minor associated with increased risky tanning
      behaviors and burning? An exploratory study.
AB  - Tanning bed use is most common among youth and young adults, and is associated
      with an increased risk of skin cancer. Recently, numerous states have adopted
      restrictions on minors' access to tanning beds; however, little has been reported
      on how such policies may impact tanning behaviors and burning. The purpose of
      this study was to examine the associations between age of indoor tanning
      initiation and risky tanning behaviors and burning. Female students (n=567)
      attending a large southeastern public university completed a questionnaire
      (spring of 2015) assessing tanning bed use history, including age of initiation.
      The analytic sample was limited to participants reporting past year indoor
      tanning (n=134). Multivariable logistic regression was used to compare the odds
      of risky tanning behaviors and burning among those initiating indoor tanning
      before and after their 18th birthday. Participants initiating indoor tanning as a
      minor had significantly (ps<0.05) greater odds of using a tanning bed 10 or more
      times in the previous year, typically indoor tanning for >=10min, ever indoor
      tanning without wearing goggles, and ever fallen asleep inside a tanning bed.
      Further, those that initiated as a minor had significantly greater odds of ever
      burning from indoor tanning (p<0.05). Indoor tanning initiation as a minor was
      associated with several risky tanning behaviors and burning. Youth access
      restrictions may help reduce the harms caused by tanning beds.

PMID- 28757449
TI  - Weight loss in the prevention and treatment of diabetes.
AB  - The American Diabetes Association nutrition and lifestyle recommendations for
      prediabetes and type 2 diabetes focus on losing 7% of body weight and increasing
      physical activity to at least 150minperweek. This emphasis is largely based on
      results of the Diabetes Prevention Program (DPP) and Look AHEAD (Action for
      Health in Diabetes) clinical trials. DPP demonstrated that a lifestyle
      intervention aimed at 7% weight loss and 150min of activity per week reduced
      diabetes incidence by 58% after 2.8years of follow-up and resulted in sustained
      improvements in hemoglobinA1c, blood pressure and lipid levels. After 15years of
      follow-up, DPP's lifestyle intervention sustained a 27% risk reduction in
      progression to diabetes. Look AHEAD's lifestyle intervention significantly
      reduced hemoglobinA1c, blood pressure, triglycerides, and the amount and costs of
      medications needed to treat these conditions when compared with diabetes support
      and education. Other clinical and psychological benefits achieved with lifestyle
      intervention were greater reductions in c-reactive protein, less self-reported
      retinopathy, reduced risk of nephropathy, less sexual dysfunction, decreased
      incidence of urinary incontinence and fatty liver, remission of sleep apnea,
      better physical functioning, less knee pain, more remission of diabetes, reduced
      incidence of depression, less body image dissatisfaction and improved quality-of
      life. A number of DPP translation studies have demonstrated weight losses of 4 to
      7% at 6month and 1year follow-up which has led to Medicare coverage for CDC
      recognized DPP lifestyle programs starting in April 2018. Translation studies of
      Look AHEAD using a variety of delivery formats are underway.

PMID- 28757451
TI  - Six years' experience of tolerance induction in renal transplantation using stem
      cell therapy.
AB  - Tolerance induction (TI) has been attempted with chimerism/clonal deletion. We
      report results of TI protocol (TIP) using stem cell therapy (SCT) included
      adipose derived mesenchymal stem cells (AD-MSC) and hematopoietic stem cells
      (HSC) in 10 living-donor related renal transplantation (LDRT) patients under non
      myeloablative conditioning with Bortezomib, Methylprednisone, rabbit-anti
      thymoglobulin and Rituximab, without using conventional immunosuppression.
      Transplantation was performed following acceptable lymphocyte cross-match, flow
      cross-match, single antigen assay and negative mixed lymphocyte reaction (MLR).
      Monitoring included serum creatinine (SCr), donor specific antibodies (DSA) and
      MLR. Protocol biopsies were planned after 100days and yearly in willing patients.
      Rescue immunosuppression was planned for rejection/DSA/positive MLR. Over mean
      6+/-0.37year follow-up patient survival was 80% and death-censored graft survival
      was 90%. Mean SCr was 1.44+/-0.41mg/dL. This is the first clinical report of
      sustained TI in LDRT for 6years using SCT.

PMID- 28757450
TI  - Applying behavior change techniques to weight management during pregnancy: Impact
      on perinatal outcomes.
AB  - Unhealthy behaviors and lifestyle choices are contributing to the obesity
      epidemic and associated morbidities. Among reproductive aged women, obesity
      adversely affects perinatal outcomes and longer term maternal and child health.
      Interventions utilizing strategies of behavior change have the potential to
      improve outcomes, especially during pregnancy. Antenatal interventions to improve
      adherence to gestational weight gain guidelines are one such example. Although
      behaviorally-based intervention trials have been associated with modest decreases
      in gestational weight gain, the effect on short term perinatal outcomes has thus
      far been minimal. This commentary aims to discuss possible reasons behind the
      failure to improve perinatal outcomes as well as to encourage future areas of
      study.

PMID- 28757452
TI  - Will we ever have better glucocorticoids?
AB  - Glucocorticoids are cost-effective drugs with potent anti-inflammatory and
      immunosuppressive effects. They are used successfully to treat many disorders,
      including rheumatoid arthritis, polymyalgia rheumatic and other rheumatic
      diseases. However, these drugs also have the potential to cause adverse effects,
      particularly if high doses are used for prolonged periods. Therefore, continuous
      efforts are being made to implement recommendations for optimal dosing of
      glucocorticoids, monitoring for potential adverse events, adverse event
      prevention and management. Apart from this, novel and interesting work is
      underway to develop innovative glucocorticoids or glucocorticoid receptor ligands
      in order to improve the therapeutic balance. This article briefly mentions a
      recent publication discussing the question under which conditions long-term
      treatment with glucocorticoids has an acceptably low level of harm, and focuses
      then on two current approaches to minimize glucocorticoid adverse effects while
      keeping or even enhancing their anti-inflammatory efficacy, liposomal
      glucocorticoids and dissociated agonists of the glucocorticoid receptor.

PMID- 28757454
TI  - The neurocognitive consequences of sleep restriction: A meta-analytic review.
AB  - The current meta-analytic review evaluated the effects of experimentally
      manipulated sleep restriction on neurocognitive functioning. Random-effects
      models were employed to estimate the overall effect size and the differential
      effect size across cognitive domains. Age, time of day, age-adjusted sleep
      deficit, cumulative days of restricted sleep, sleep latency, subjective
      sleepiness, and biological sex were examined as potential moderators of the
      effect. Based on a sample of 61 studies, from 71 different populations, findings
      revealed a significant negative effect of sleep restriction on cognitive
      processing across cognitive domains (g=-0.383, p<0.001). This effect held for
      executive functioning (g=-0.324, p<0.001), sustained attention (g=-0.409,
      p<0.001), and long-term memory (g=-0.192, p=0.002). There was insufficient
      evidence to detect an effect within the domains of attention, multitask,
      impulsive decision-making or intelligence. Age group, time of day, cumulative
      days of restricted sleep, sleep latency, subjective sleepiness, and biological
      sex were all significant moderators of the overall effect. In conclusion, the
      current meta-analysis is the first comprehensive review to provide evidence that
      short-term sleep restriction significantly impairs waking neurocognitive
      functioning.

PMID- 28757453
TI  - lnc133b, a novel, long non-coding RNA, regulates bovine skeletal muscle satellite
      cell proliferation and differentiation by mediating miR-133b.
AB  - The proliferation and differentiation of skeletal muscle satellite cells is
      regulated by multiple regulatory factors including non-coding RNAs. It has been
      reported that miR-133b regulates myogenesis. In this study, we detected a novel
      lncRNA, lnc133b, which is completely complemented by mature miR-133b, indicating
      that lnc133b may regulate the expression of miR-133b by "sponge" miR-133b. A
      luciferase report assay confirmed that lnc133b interacts with miR-133b in regions
      complemented by miR-133b. We successfully constructed lnc133b gain/loss-of
      function cell models by infecting LV-1nc133b and transfecting si-lnc133b into
      satellite cells. Results of quantitative real-time polymerase chain reaction (qRT
      PCR) and 5-ethynyl-2'-deoxyuridine (EdU) assays showed that overexpression or
      inhibition of lnc133b could promote the proliferation or inhibition of satellite
      cell differentiation. The qRT-PCR results also showed that lnc133b negatively
      regulates miR-133b expression and a Western blot assay showed that lnc133b
      positively regulates IGF1R expression, indicating that the lnc133b/miR-133b/IGF1R
      axis is a potential pathway for promoting satellite cell proliferation and
      repressing their differentiation through the ceRNA mechanism. Building on the
      findings of previous reports, we constructed the lnc133b/miR-133b/FGFR1 & PP2AC
      pathway to improve the lnc133b regulation network regulating the proliferation
      and differentiation of satellite cells. The current study provides a new
      perspective for understanding the mechanism regulating satellite cell
      proliferation and differentiation through the interaction of miR-133b and
      lnc133b.

PMID- 28757455
TI  - Affordances and neuroscience: Steps towards a successful marriage.
AB  - The concept of affordance is rapidly gaining popularity in neuroscientific
      accounts of perception and action. This concept was introduced by James Gibson to
      refer to the action possibilities of the environment. By contrast, standard
      cognitive neuroscience typically uses the concept to refer to (action-oriented)
      representations in the brain. This paper will show that the view of affordances
      as representations firmly places the concept in the subject-object framework that
      dominates both psychology and neuroscience. Notably, Gibson introduced the
      affordance concept to overcome this very framework. We describe an account of the
      role of the brain in perception and action that is consistent with Gibson. Making
      use of neuroscientific findings of neural reuse, degeneracy and functional
      connectivity, we conceptualize neural regions in the brain as dispositional parts
      of perceptual and action systems that temporarily assemble to enable animals to
      directly perceive and - in the paradigmatic case - utilize the affordances of the
      environment.

PMID- 28757456
TI  - Prenatal developmental origins of behavior and mental health: The influence of
      maternal stress in pregnancy.
AB  - Accumulating research shows that prenatal exposure to maternal stress increases
      the risk for behavioral and mental health problems later in life. This review
      systematically analyzes the available human studies to identify harmful
      stressors, vulnerable periods during pregnancy, specificities in the outcome and
      biological correlates of the relation between maternal stress and offspring
      outcome. Effects of maternal stress on offspring neurodevelopment, cognitive
      development, negative affectivity, difficult temperament and psychiatric
      disorders are shown in numerous epidemiological and case-control studies.
      Offspring of both sexes are susceptible to prenatal stress but effects differ.
      There is not any specific vulnerable period of gestation; prenatal stress effects
      vary for different gestational ages possibly depending on the developmental stage
      of specific brain areas and circuits, stress system and immune system. Biological
      correlates in the prenatally stressed offspring are: aberrations in
      neurodevelopment, neurocognitive function, cerebral processing, functional and
      structural brain connectivity involving amygdalae and (pre)frontal cortex,
      changes in hypothalamo-pituitary-adrenal (HPA)-axis and autonomous nervous
      system.

PMID- 28757458
TI  - A computational integrative approach based on alternative splicing analysis to
      compare immortalized and primary cancer cells.
AB  - Immortalized cell lines are widely used to study the effectiveness and toxicity
      of anti cancer drugs as well as to assess the phenotypic characteristics of
      cancer cells, such as proliferation and migration ability. Unfortunately, cell
      lines often show extremely different properties than tumor tissues. Also the
      primary cells, that are deprived of the in vivo environment, might adapt to
      artificial conditions, and differ from the tissue they should represent. Despite
      these considerations, cell lines are still one of the most used cancer models due
      to their availability and capability to expand without limitation, but the
      clinical relevance of their use is still a big issue in cancer research. Many
      studies tried to overcome this task, comparing cell lines and tumor samples
      through the definition of the genomic and transcriptomic differences. To this
      aim, most of them used nucleotide variation or gene expression data. Here we
      introduce a different strategy based on alternative splicing detection and
      integration of DNA and RNA sequencing data, to explore the differences between
      immortalized and tissue-derived cells at isoforms level. Furthermore, in order to
      better investigate the heterogeneity of both cell populations, we took advantage
      of a public available dataset obtained with a new simultaneous omics single cell
      sequencing methodology. The proposed pipeline allowed us to identify, through a
      computational and prediction approach, putative mutated and alternative spliced
      transcripts responsible for the dissimilarity between immortalized and primary
      hepato carcinoma cells.

PMID- 28757459
TI  - Radiofrequency magnetic resonance coils and communication antennas: Simulation
      and design strategies.
AB  - Coils simulation and design is a fundamental task to maximize Signal-to-Noise
      Ratio in Magnetic Resonance applications. In the meantime, in the last years the
      issue of accurate communication antennas analysis has grown. Coil design
      techniques take advantage of computer simulations in dependence on the magnetic
      field wavelength and coil sizes. In particular, since at high frequencies coils
      start to behave as antennas, modern Magnetic Resonance coil development exploits
      numerical methods typically employed for antennas simulation. This paper reviews
      coil and antenna performance parameters and focuses on the different simulation
      approaches in dependence on the near/far field zones and operating frequency.

PMID- 28757460
TI  - Critical role of p21 on olaquindox-induced mitochondrial apoptosis and S-phase
      arrest involves activation of PI3K/AKT and inhibition of Nrf2/HO-1pathway.
AB  - Olaquindox, a quinoxaline 1,4-di-N-oxide, is known as an antibacterial agent and
      feed additive to treat bacterial infections and promote animal growth. However,
      the potential mechanism of toxicity is still unknown. The present study aims to
      explore the molecular mechanism of p21 on olaquindox-induced mitochondrial
      apoptosis and S-phase arrest in human hepatoma G2 cells (HepG2). As a result,
      olaquindox promoted production of ROS, suppressed the protein expression p21 in
      p53-independent way and phosphorylated p21. Meanwhile, olaquindox activated AKT
      and Nrf2/HO-1 pathway, up-regulated Bax/Bcl-2 ratio, disrupted mitochondrial
      membrane potential (MMP) and subsequently caused cytochrome c release and a
      cascade activation of caspase, eventually induced apoptosis. Olaquindox could
      induce S-phase arrest in HepG2 cells involved with the increase of Cyclin A,
      Cyclin E and CDK 2. Furthermore, knockdown of p21 decreased cell viability,
      enhanced oxidative stress, aggravated olaquindox-induced mitochondrial apoptosis
      and S-phase arrest involvement of activating PI3K/AKT and inhibiting Nrf2/HO-1
      pathway. PI3K/AKT inhibitor (LY294002) and HO-1inhibitor (ZnPP-IX) both increased
      olaquindox-induced apoptosis and S-phase arrest. In conclusion, knockdown of p21
      increased olaquindox-induced mitochondrial apoptosis and S-phase arrest through
      further activating PI3K/AKT and inhibiting Nrf2/HO-1pathway. Our study provided
      new insights into the molecular mechanism of olaquindox and shed light on the
      role of p21.

PMID- 28757461
TI  - Safety assessment of Urolithin A, a metabolite produced by the human gut
      microbiota upon dietary intake of plant derived ellagitannins and ellagic acid.
AB  - Urolithins are metabolites produced in the gut following consumption of
      ellagitannins and ellagic acid rich foods such as pomegranates, nuts and certain
      berries. Urolithin A (UA) is one of the predominant isoforms of urolithins in
      humans and has demonstrated compelling biological activities, suggesting
      potential benefits of direct consumption of UA. However, an evaluation of the
      safety of direct administration of UA has not yet been published. The aim of this
      study was to investigate for the first time the genotoxicity, toxicokinetics, and
      repeated dose safety of orally administered synthetic UA in rats. The battery of
      genotoxicity assays demonstrated that UA is not genotoxic. The ADME study showed
      that glucuronidated and sulfonated forms of UA are the predominant metabolites
      following both oral and i.v. administration. The 28-day (0, 0.175, 1.75, and 5.0%
      UA mixed in diet) and 90-day studies (0, 1.25, 2.5, and 5.0% UA mixed in diet)
      showed no alterations in clinical parameters, blood chemistry, or hematology, and
      did not indicate any target organs, or any specific toxic mechanisms. The NOAEL
      was the highest dose tested, 5% UA by weight in the diet, or 3451 mg/kg bw/day in
      males and 3826 mg/kg bw/day in females in the 90-day oral study.

PMID- 28757457
TI  - Dual-transmitter systems regulating arousal, attention, learning and memory.
AB  - An array of neuromodulators, including monoamines and neuropeptides, regulate
      most behavioural and physiological traits. In the past decade, dramatic progress
      has been made in mapping neuromodulatory circuits, in analysing circuit dynamics,
      and interrogating circuit function using pharmacogenetic, optogenetic and imaging
      methods This review will focus on several distinct neural networks
      (acetylcholine/GABA/glutamate; histamine/GABA; orexin/glutamate; and relaxin
      3/GABA) that originate from neural hubs that regulate wakefulness and related
      attentional and cognitive processes, and highlight approaches that have
      identified dual transmitter roles in these behavioural functions. Modulation of
      these different neural networks might be effective treatments of diseases related
      to arousal/sleep dysfunction and of cognitive dysfunction in psychiatric and
      neurodegenerative disorders.

PMID- 28757462
TI  - Innocuousness of a polyherbal formulation: A case study using a traditional Thai
      antihypertensive herbal recipe in rodents.
AB  - Recently, a traditional Thai antihypertensive herbal recipe has reportedly been
      used in Thailand. Its ingredients have long featured in traditional Thai medicine
      preparations; however, research indicates that the presence of one of them -
      Tinospora crispa - may have negative effects on the liver and kidneys. Thus, the
      safety data of this recipe must be proved in animal models prior to conducting
      any studies in humans. The present case study aims to evaluate the safety of this
      recipe in Swiss albino mice and Wistar rats through acute and sub-chronic
      toxicity studies, respectively. The quality control of this recipe was also
      achieved to guarantee the chemical consistency throughout the entire experiment.
      Results showed that this recipe did not cause death or any toxic signs in mice or
      rats. The oral LD50 value in mice was more than 5.0 g/kg. Some hematological and
      serum biochemical values of treated rats, such as hematocrit, hemoglobin,
      platelet, monocytes, aspartate aminotransferase, bilirubin, and creatinine, were
      found to be statistically different from the control group; however, all values
      were within the ranges of normal rats. Considering the histological study, no
      damage on liver and kidney tissues was observed in the treatment.

PMID- 28757464
TI  - An online 2D-reversed-phase - Reversed-phase chromatographic method for sensitive
      and robust plasma protein quantitation.
AB  - Offline high-pH reversed-phase fractionation is widely used to reduce sample
      complexity in proteomic workflows. This is due to the semi-orthogonality and high
      peak resolution of the two separations. Offline 2D fractionation, however, is low
      throughput and requires several manual manipulations and is prone to sample
      losses. To address these issues, we developed an online two dimensional high-pH -
      low-pH reversed-phase-reversed-phase (2D RPRP) LC-MRM method whereby hundreds of
      peptides can be quantified in a single LC-MS/MS injection. The method allowed the
      reproducible and sensitive quantitation of a test panel of 367 peptides (168
      proteins) from undepleted and non-enriched human plasma. Of these, we were able
      to detect and quantify 95 peptides (29 proteins) by 2D-RPRP that were not
      detectable by 1D LC-MRM-MS. Online 2D RPRP resulted in an average increase of
      roughly 10-fold in sensitivity compared to traditional 1D low-pH separations,
      while improving reproducibility and sample throughput relative to offline 2D RPRP
      by factors of 1.7 and 5, respectively, compared to offline 2D RPRP. This paper
      serves as proof-of-concept of the feasibility and efficacy of online 2D RPRP at
      analytical flow rates for highly multiplexed targeted proteomic analyses.

PMID- 28757463
TI  - Permethrin alters glucose metabolism in conjunction with high fat diet by
      potentiating insulin resistance and decreases voluntary activities in female
      C57BL/6J mice.
AB  - Permethrin, a type 1 pyrethroid insecticide, was previously reported to promote
      adipogenesis in 3T3-L1 adipocytes and insulin resistance in C2C12 muscle cells;
      however, the effects of permethrin exposure on glucose and lipid metabolisms in
      vivo remain unknown. The purpose of this study was to investigate the effects of
      permethrin exposure on glucose and lipid homeostasis as well as voluntary
      movement in female mice in response to dietary fat. We tested three doses of
      permethrin (50, 500, & 5000 MUg/kg body weight/day) in low fat diet-fed (4% w/w
      of diet) and high fat diet-fed (20% w/w of diet) female C57BL/6 J mice for twelve
      weeks. Our results demonstrated that permethrin treatment potentiated high fat
      diet-induced insulin resistance as indicated by insulin tolerance tests, glucose
      tolerance tests, and homeostasis model assessment - insulin resistance (HOMA-IR)
      without altering weight or fat mass. Permethrin treatment significantly decreased
      voluntary movement and elevated blood glucose and insulin levels. Western blot
      results further showed that permethrin impaired insulin signaling via the Akt
      signaling pathway in the gastrocnemius muscle. Taken together, these results
      suggest that oral administration of permethrin potentiated high fat diet-induced
      insulin resistance, possibly increasing the risk of type 2 diabetes without
      altering weight gain in female C57BL/6 J mice.

PMID- 28757465
TI  - Mini-encyclopaedia of the wound healing - Opportunities for integrating multi
      omic approaches into medical practice.
AB  - : Wound healing is a highly complex life-important repair process triggered by
      plenty of local and/or systemic organ and tissue damaging events, such as an
      acute surgical invasion, accidental organ and tissue damages, acute and chronic
      diseases, aggressive local and systemic therapeutic approaches (e.g. irradiation
      and systemic chemotherapy). Individual health condition determines over the
      quality of wound healing. Impaired wound healing, in turn, may lead, for example,
      to post-surgical complications frequently observed in elderly, chronic ulcers in
      diabetic patients, hindered and ineffective pain management, etc. However, these
      well-acknowledged examples are just the tip of the iceberg. The entire spectrum
      of potential consequences is much broader. Therefore, all the aspects of wound
      healing need to receive a dedicated attention of many specialised medical fields
      and healthcare as a whole. In contrast, there is still strongly limited knowledge
      collected regarding the molecular and cellular mechanisms underlying the
      physiological versus impaired wound healing. The contents of this article might
      be of great importance for multi-professional considerations as well as for the
      experts working in specific fields such as clinical proteomics, general practice,
      laboratory medicine, surgery including plastic surgery and aesthetic medicine,
      gerontology, psychology, diabetology, endocrinology, oncology, cardiovascular
      disease, radiology, and healthcare economy. SIGNIFICANCE: The contents of this
      article are strongly motivated by the particular value of wound healing quality
      for medical care and might be of great importance for multi-professional
      considerations and experts working in specialised fields: predictive and
      preventive medicine, general practitioners, laboratory medicine, surgery
      including plastic surgery and aesthetic medicine, gerontology, psychology,
      diabetology, endocrinology, oncology, cardiovascular disease, radiology, and
      healthcare economy. The article is aiming at both educational and scientific
      purposes: on one side it summarises comprehensive information available regarding
      wound healing mechanisms and molecular pathways involved. On the other side the
      article provides highly innovative hypotheses for multi-professional
      considerations relevant for several research fields which may potentially advance
      medical services in the close future such as clinical proteomics and multi-omics.

PMID- 28757466
TI  - Identification of serum proteome signature of irritable bowel syndrome: Potential
      utility of the tool for early diagnosis and patient's stratification.
AB  - : Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder with high
      incidence, and great heterogeneity of symptoms. Numerous factors are correlated
      with IBS development; however, the pathophysiology is not yet clear. In addition,
      there is no appropriate diagnostic tool available. The aim of this study was the
      identification of protein expression alterations in IBS patients compared to
      healthy individuals. Serum samples from 30 IBS patients (10 with IBS-Diarrhea, 10
      IBS-Constipation and 10 IBS-Mixed) and 10 healthy individuals were subjected to
      proteomic analysis by 2-dimensional gel electrophoresis. Following evaluation of
      densitometrical data, protein spots exhibiting differential expression among the
      groups, were further characterized by matrix-assisted laser desorption tandem
      time-of-flight mass spectrometer and the results were confirmed by Western blot
      analysis. Eight significantly different expressed proteins were identified. Seven
      of them were overexpressed in IBS cases and only one was overexpressed in healthy
      individuals. These proteins were also differently expressed between the three IBS
      subgroups. IBS-D group overexpressed immunoglobulin light chain Lambda (LAC3) and
      apolipoprotein E (APOE), IBS-C group overexpressed apolipoprotein H (APOH) and
      collagen alpha-1 (XIV) chain (COEA1), and IBS-M group and healthy individuals
      overexpressed retinol-binding protein 4 (RET4). Our results show a different
      serum protein profile of IBS patients compared to healthy controls. Understanding
      the role of these eight proteins which are differently expressed in IBS patients,
      may contribute to a better clarification of IBS pathogenesis and to patient's
      stratification. SIGNIFICANCE: Irritable bowel syndrome (IBS) is a chronic
      gastrointestinal disorder with high incidence and great heterogeneity of symptoms
      without any appropriate diagnostic tool available. Eight significantly different
      expressed proteins were identified. Seven of them were overexpressed in IBS cases
      and only one was expressed in healthy individuals. These proteins were also
      differently expressed between the three IBS subgroups. Our results show that
      there is a different serum proteome signature in IBS compared to healthy
      individuals, as well as in IBS subgroups that could be used in the future for
      patient's stratification and as a diagnostic tool.

PMID- 28757467
TI  - High-level expression and purification of soluble form of human natural killer
      cell receptor NKR-P1 in HEK293S GnTI- cells.
AB  - Human natural killer receptor protein 1 (NKR-P1, CD161, gene klrb1) is a C-type
      lectin-like receptor of natural killer (NK) cells responsible for recognition of
      its cognate protein ligand lectin-like transcript 1 (LLT1). NKR-P1 is the single
      human orthologue of the prototypical rodent NKR-P1 receptors. Naturally, human
      NKR-P1 is expressed on the surface of NK cells, where it serves as inhibitory
      receptor; and on T and NKT cells functioning as co-stimulatory receptor promoting
      secretion of IFNgamma. Most notably, it is expressed on Th17 and Tc17 lymphocytes
      where presumably promotes targeting into LLT1 expressing immunologically
      privileged niches. We tested effect of different protein tags (SUMO, TRX, GST,
      MsyB) on expression of soluble NKR-P1 in E. coli. Then we optimized the
      expression construct of soluble NKR-P1 by preparing a library of expression
      constructs in pOPING vector containing the extracellular lectin-like domain with
      different length of the putative N-terminal stalk region and tested its
      expression in Sf9 and HEK293 cells. Finally, a high-level expression of soluble
      NKR-P1 was achieved by stable expression in suspension-adapted HEK293S GnTI-
      cells utilizing pOPINGTTneo expression vector. Purified soluble NKR-P1 is
      homogeneous, deglycosylatable, crystallizable and monomeric in solution, as shown
      by size-exclusion chromatography, multi-angle light scattering and analytical
      ultracentrifugation.

PMID- 28757468
TI  - Identification, cloning and expression analysis of an alpha-CGTase produced by
      stain Y112.
AB  - Cyclodextrin glycosyltransferase (CGTase) is an enzyme able to convert starch and
      other substrates into cyclodextrins (CDs). A marine strain Y112 producing alpha
      CGTase was identified as Bacillus agaradhaerens Y112 by physiological and
      biochemical characterization, and 16S rDNA analysis. The gene coding for alpha
      CGTase was cloned, sequenced and expressed in Escherichia coli BL21 (DE3) cells.
      Recombinant alpha-CGTase was purified in one-step chromatographic separation and
      its purity evaluated by SDS-PAGE, showing the presence of one band with a
      molecular mass of about 92 kDa. Additionally, enzymatic capability was analyzed
      by measuring the starch conversion, and resulted in about 45% of CDs obtained
      after 6 h of cyclodextrin reaction. Of these CDs, mainly alpha-CD was produced
      (70% of the total CDs yield), suggesting the potential of this CGTase for
      industrial applications.

PMID- 28757469
TI  - The discovery and expansion of Hippo signaling pathway in Drosophila model.
AB  - The discovery of Hippo signaling pathway is another breakthrough of fly genetics.
      Similar to the other signaling pathways, Hippo pathway also functions crucially
      in tremendous physiological and pathological conditions, like organ size control
      and cancer. There are three main stages of Hippo pathway study: Firstly,
      identifications of core components by fly genetic screens; secondly, regulations
      by versatile upstream cues, like cytoskeleton, mechanical tension, and nutrition;
      thirdly, functions in different biological processes, like cell proliferation
      regulation, stem cell biology, and immunology. In this review, we summarize the
      current understanding of Hippo pathway and highlight its regulations and
      transcriptional complex assembly. We also discuss the potential future directions
      in Drosophila model system.

PMID- 28757470
TI  - Molecular mechanisms of the mammalian Hippo signaling pathway.
AB  - The Hippo pathway plays an evolutionarily conserved fundamental role in
      controlling organ size in multicellular organisms. Importantly, evidence from
      studies of patient samples and mouse models clearly indicates that deregulation
      of the Hippo signaling pathway plays a crucial role in the initiation and
      progression of many different types of human cancers. The Hippo signaling pathway
      is regulated by various stimuli, such as mechanical stress, G-protein coupled
      receptor signaling, and cellular energy status. When activated, the Hippo kinase
      cascade phosphorylates and inhibits the transcription co-activator YAP (Yes
      associated protein), and its paralog TAZ (transcriptional coactivator with PDZ
      binding motif), resulting in their cytoplasmic retention and degradation. When
      the Hippo signaling pathway is inactive, dephosphorylated YAP/TAZ translocate
      into the nucleus and activate gene transcription through binding to TEAD (TEA
      domain) family and other transcription factors. Such changes in gene expression
      promote cell proliferation and stem cell/progenitor cell self-renewal but inhibit
      apoptosis, thereby coordinately promote increase in organ size, tissue
      regeneration, and tumorigenesis. In this review, we summarize the molecular
      mechanisms of the mammalian Hippo signaling pathway with special emphasis on the
      Hippo kinase cascade and its upstream signals, the Hippo signaling pathway
      regulation of YAP and the mechanisms of YAP in regulation of gene transcription.

PMID- 28757471
TI  - The emerging Hippo signaling pathway in plants.
AB  - How the organ size is determined is a fundamental question in developmental
      biology. The metazoan Hippo signaling pathway is well established to negatively
      regulate organ sizes. Recent studies in plants have started to shape an emerging
      Hippo signaling pathway. In this review, we summarize the studies in the past
      decade on the two known components of plant Hippo signaling pathway, the
      Ste20/Hippo homolog SIK1, and the MOB1/Mats homolog MOB1, with a focus on their
      developmental functions. Then we envision future discoveries that may shape a
      complete Hippo signaling pathway in plants.

PMID- 28757472
TI  - Hippo signaling pathway in cardiovascular development and diseases.
AB  - Cardiovascular diseases have become the leading cause of death in the world.
      Understanding the development of cardiovascular system and the pathogenesis of
      cardiovascular diseases will promote the generation of novel preventive and
      therapeutic strategy. The Hippo pathway is a recently identified signaling
      cascade that plays a critical role in organ size control, cell proliferation,
      apoptosis and fate determination of stem cells. Gene knockout and transgenic
      mouse models have revealed that the Hippo signaling pathway is involved in heart
      development, cardiomyocyte proliferation, apoptosis, hypertrophy and cardiac
      regeneration. The Hippo signaling pathway also regulates vascular development,
      differentiation and various functions of vascular cells. Dysregulation of the
      Hippo signaling pathway leads to different kinds of cardiovascular diseases, such
      as myocardial infarction, cardiac hypertrophy, neointima formation and
      atherosclerosis. In this review, we briefly summarize current research on the
      roles and regulation mechanisms of the Hippo signaling pathway in cardiovascular
      development and diseases.

PMID- 28757473
TI  - Functions and regulations of the Hippo signaling pathway in intestinal
      homeostasis, regeneration and tumorigenesis.
AB  - The intestine is an important digestive organ. Intestinal diseases such as acute
      or chronic enteritis and colorectal cancer pose a great threat to human health,
      which endows the studies related to intestine with great scientific and clinical
      value. The Hippo signaling pathway plays an important role in proliferation and
      differentiation of intestinal stem cells, and is involved in diverse
      physiological and pathological processes in the intestine. In this review, we
      summarize known functions and mechanisms of the Hippo signaling pathway in
      intestinal regeneration and tumorigenesis, provide a prospective on future
      research directions, and discuss potential therapeutic strategies targeting the
      Hippo signaling pathway.

PMID- 28757474
TI  - Hippo signaling pathway in lung development, regeneration, and diseases.
AB  - function between the circulation and the atmospheric environment. Lung diseases,
      including lung cancer, are among the leading causes of death in the modern
      society. Research on lung development, regeneration and cancer could provide
      significant insights for the development of therapeutic approaches on lung
      diseases. Hippo/YAP/TAZ signaling pathway regulates cell proliferation and
      differentiation, controls organ size, and plays an important role in response to
      mechanical forces. YAP/TAZ are expressed in many cell types and serve various
      regulatory functions in the embryonic and adult lungs. In this review, we mainly
      focus on the roles of Hippo/YAP/TAZ signaling pathway in embryonic lung
      development, regeneration and cancer. We postulate that Hippo/YAP/TAZ signaling
      may play potential roles in regulating the alveolar mechanics and immune
      responses in the lung.

PMID- 28757475
TI  - Hippo signaling pathway in liver tissue homeostasis.
AB  - Liver cancer and diseases have become the leading cause of deaths in China. Liver
      diseases including liver failure and liver cancer can be genetic or caused by a
      variety of factors that damage the liver, such as viruses and alcohol overdose.
      However, the underlying mechanisms that maintain liver homeostasis remain
      unclear. Recent studies show that the Hippo signaling pathway plays a critical
      role in maintaining liver tissue homeostasis. Dysregulation of the Hippo
      signaling pathway impairs liver regeneration and remarkly enhances liver
      overgrowth and tumorigenesis. In this review, we summarize recent progresses on
      the roles and regulation mechanisms of the Hippo signaling pathway in liver
      development and diseases.

PMID- 28757476
TI  - The regulatory mechanisms and functional roles of the Hippo signaling pathway in
      breast cancer.
AB  - Hippo signaling pathway has attracted broad attention due to its essential roles
      in controlling organ size and tumorigenesis. TAZ/YAP, two core downstream
      molecules of the Hippo signaling pathway in mammals, are tightly regulated by a
      wide range of extracellular and intrinsic signals in both Hippo signaling pathway
      dependent and -independent manners. Besides their roles in the development and
      function of normal mammary glands, TAZ/YAP display remarkable potency and
      relevance to multiple aspects of human breast carcinogenesis, including cellular
      proliferation, differentiation, apoptosis, migration, invasion, epithelial
      mesenchymal transition and stemness. In this review, we summarize the regulators
      of TAZ/YAP, discuss the significant contribution of the Hippo signaling pathway
      to human breast cancers and highlight their potential therapeutic roles.

PMID- 28757477
TI  - The roles and mechanisms of the Hippo/YAP signaling pathway in the nervous
      system.
AB  - The Hippo signaling pathway, consisting of a highly conserved kinase cascade and
      downstream transcription co-activators YAP (Yes-associated protein)/TAZ
      (transcriptional coactivator with PDZ-binding motif), plays a key role in tissue
      homeostasis and organ size control by regulating the proliferation,
      differentiation and apoptosis of cells. During normal development, the precise
      control of neural cell numbers and spatial distributions of these neural cells is
      important for brain development. Recent studies have shown that the Hippo/YAP
      signaling pathway is actively involved in the self-renewal of neural stem cells,
      proliferation of neural progenitor cells, differentiation and activation of glial
      cells, and myelination of glial cells as well as in the development of
      neurological diseases. Due to its prominent role in the nervous system, it is
      necessary to further study on this pathway. In this review, we summarize the
      recent studies and focus on the roles and mechanisms of the Hippo/YAP signaling
      pathway in the nervous system, and provide insights for neural development and
      neural injury diseases.

PMID- 28757478
TI  - The roles and mechanisms of MST1/2 in the innate immune response.
AB  - The Hippo signaling pathway regulates cell proliferation, organ size and tissue
      regeneration through a series of kinase cascades. MST1/2 is the mammalian
      orthologue of the core kinase Hippo, which is crucial for the activation of
      downstream signaling. Additionally, MST1/2 has been reported to play important
      roles in cell differentiation, morphology and cytoskeleton reorganization. Recent
      evidence suggests that MST1/2 is involved in the regulation of T cell adhesion,
      migration, homing and Treg cell maturation and functions. Interestingly, these
      processes are not dependent on the canonical, but a non-canonical Hippo signaling
      pathway. More recent studies have revealed that MST1/2 mediates the innate immune
      response against pathogens or viruses, especially on macrophage phagocytosis as
      well as cytokines and ROS production. MST1/2 is associated with various diseases,
      such as bacterial or viral infection, inflammation-related cancer, and
      atherosclerosis. In this review, we summarize recent findings on the functions of
      MST1/2 in the innate immune response and inflammation-related diseases.

PMID- 28757479
TI  - The functions of the Hippo signaling pathway in immune cells.
AB  - The Hippo signaling pathway, first identified in Drosophila, has emerged as a
      critical regulator for controlling the size of organs. Activation of the Hippo
      signaling pathway negatively regulates the Yorkie ortholog YAP in multiple
      organs, important in the regulation of cell proliferation, differentiation, and
      apoptosis during development. The Serine/Threonine protein kinases MST1 and MST2,
      mammalian homologs of the Drosophila Hippo kinase, play central roles in the
      Hippo signaling pathway in mammals. Recent studies reveal that non-canonical
      Hippo signaling pathways are also involved in the regulation of various other
      biological processes, particularly the important roles of MST1 and MST2 kinases
      in immune cell activation, adhesion, migration, growth, and apoptosis. In this
      review, we summarize the recent advances in understanding the roles of MST1 and
      MST2 kinases in the regulation of the functions of T lymphocytes and innate
      immune cells.

PMID- 28757480
TI  - Research progresses on the molecular structure of the Hippo signaling pathway
      components.
AB  - The Hippo signaling pathway has been identified to be involved in development and
      tissue homeostasis during the past decade, and is evolutionarily conserved from
      Drosophila to mammals. It transduces the signal through a series of protein
      protein interaction and kinase cascades, to control the cell number and organ
      size by inhibiting cell proliferation and promoting apoptosis. Dysregulation of
      the Hippo signaling pathway is associated with tumorigenesis and cancers, so it
      is a crucial target for cancer therapy and regeneration medicine. Most of the
      Hippo signaling pathway components have been identified, and the cellular
      function and molecular mechanism have been revealed by structural and functional
      researches. In this review, we summarize the molecular structure of Hippo
      signaling pathway components and related targeting inhibitors from a structural
      view. We hope to improve the understandings of the regulation mechanism of the
      Hippo signaling transduction, and facilitate further functional studies and
      potential therapeutic interventions.

PMID- 28757481
TI  - The roles of YAP T425A mutation in the regulation of YAP activity.
AB  - The Hippo signaling pathway plays a critical role in body development and tissue
      growth. As the core effector of the Hippo signaling pathway, Yes-associated
      protein (YAP) has been reported to be involved in various kinds of human cancers.
      However, the mechanism for the regulation of YAP activity has not been completely
      understood. In this study, we constructed a YAP Thr425Ala mutant and found that
      this mutation decreased YAP transcriptional activity. Further, T425A retained YAP
      in the cytoplasm without affecting the phosphorylation of YAP S127. Moreover, we
      observed that the T425A mutation attenuated the ability of YAP in driving MCF10A
      cell migration. Our research indicates that T425 of YAP is important for the
      regulation of YAP localization and activity.

PMID- 28757484
TI  - "Scholasticism Is a Daughter of Judaism": The Discovery of Jewish Influence on
      Medieval Christian Thought.
AB  - This article retells the surprising discovery of a considerable Jewish influence
      on Christian scholasticism in the Middle Ages. While most students of Albert the
      Great and Thomas Aquinas knew that both had read Jewish philosophy, only the
      rediscovery of especially Maimonides's Guide of the Perplexed by Jewish
      philosophers in the nineteenth century showed the whole extent of the
      scholastics' dependence on Jewish predecessors - especially where they do not
      refer to them specifically. This Jewish discovery naturally faced Catholic
      resistance, if not denial, and turns thus into an interesting chapter in the
      history of theological ideas.

PMID- 28757482
TI  - Association Between High-Sensitivity Cardiac Troponin I and Cardiac Events in
      Elderly Women.
AB  - BACKGROUND: Elderly women are at high risk of coronary heart disease (CHD) and
      heart failure. High-sensitivity assays allow detection of cardiac troponin I
      (hsTnI) well below diagnostic cutoffs for acute coronary syndrome. We
      investigated the association between these levels with future cardiac events in
      community-based ambulant white women aged over 70 years initially recruited for a
      5-year randomized, controlled trial of calcium supplements. METHODS AND RESULTS:
      This was a prospective study of 1081 elderly women without clinical CHD at
      baseline (1998) or hsTnI above the diagnostic cutoffs for acute coronary syndrome
      with 14.5-year follow-up hospitalization and mortality (events). Two hundred
      forty-three (22%) women had CHD events, 163 (15%) myocardial infarction or CHD
      death (hard CHD), and 109 (10%) heart failure. In 99.6% of available serum
      samples, hsTnI was above the level of detection (median, 4.5 ng/L; interquartile
      range, 3.6-5.8). After adjusting for Framingham risk factors, each SD natural log
      transformed hsTnI increase was associated with an increased hazard for CHD
      (hazard ratio, 1.34; 95% CI, 1.18-1.53; P<0.001) hard CHD (hazard ratio, 1.51;
      95% CI, 1.29-1.76; P<0.001), and heart failure (hazard ratio, 1.65; 95% CI, 1.36
      1.99; P<0.001). Step-wise increases in relative hazards were observed with
      increasing quartiles of hsTnI (P for trend, <0.001), whereas the addition of
      hsTnI to conventional risk factors modestly improved discrimination indices:
      Harrell's c-statistic, net reclassification, and integrated discrimination
      (P<0.05). CONCLUSIONS: Cardiac troponin I is independently associated with future
      cardiac events in elderly women without apparent clinical manifestations. The
      addition of cardiac troponin I to conventional risk factors may modestly improve
      risk prediction in this setting.

PMID- 28757485
TI  - Francis Bacon's <i>Valerius Terminus</i> and the Voyage to the "Great
      Instauration".
AB  - Francis Bacon's earliest surviving natural philosophical treatise (composed circa
      1603) bears the title Valerius Terminus of the Interpretation of Nature. This
      study, resting on fresh attention to the surviving authorial manuscript, has
      three goals. It begins by identifying a lost precursor work apparently entitled
      "Of Active Knowledge." It then examines the significance of the pseudonyms Bacon
      chose to introduce his ideas, considering especially his invocation of Erasmus's
      emblem, the Roman deity Terminus. Finally, it shows how the Valerius Terminus's
      global vision of contemporary knowledge ultimately helped shape the iconography
      of Bacon's published Instauratio magna.

PMID- 28757486
TI  - The Picture Multiple: Figuring, Thinking, and Knowing in Descartes's
      <i>Essais</i> (1637).
AB  - Throughout his Essais (1637), Descartes appropriated the visual language of
      practical mathematics in order to forge a new natural philosophy. This article
      argues that by grafting geometric line onto descriptive figure, the philosopher
      and his illustrator, Frans van Schooten Jr., underscored doubts about a natural
      philosophy based on qualities, all the while situating his new epistemology in
      the 17th-century present and exercising a deep attention to the differences
      between nature seen, nature pictured, and nature understood.

PMID- 28757483
TI  - Association of Blood Pressure Control Level With Left Ventricular Morphology and
      Function and With Subclinical Cerebrovascular Disease.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy and subclinical cerebrovascular
      disease are early manifestations of cardiac and brain target organ damage caused
      by hypertension. This study aimed to investigate whether intensive office
      systolic blood pressure (SBP) control has beneficial effects on LV morphology and
      function and subclinical cerebrovascular disease in elderly patients with
      hypertension. METHODS AND RESULTS: We examined 420 patients treated for
      hypertension without history of heart failure and stroke from the CABL
      (Cardiovascular Abnormalities and Brain Lesions) study. All patients underwent 2
      dimensional echocardiographic examination and brain magnetic resonance imaging.
      Subclinical cerebrovascular disease was defined as silent brain infarcts and
      white matter hyperintensity volume. Patients were divided into 3 groups: SBP <120
      mm Hg (intensive control); SBP 120 to 139 mm Hg (less intensive control); and SBP
      >=140 mm Hg (uncontrolled). Prevalence of LV hypertrophy and diastolic
      dysfunction were lowest in the intensive control, intermediate in the less
      intensive control, and highest in the uncontrolled groups (12.8%, 31.8%, and
      44.7%, respectively [P<0.001], for LV hypertrophy; 46.8%, 61.7%, and 72.6%,
      respectively [P=0.003], for diastolic dysfunction). Patients with less intensive
      SBP control had greater risk of LV hypertrophy than those with intensive control
      (adjusted odds ratio, 3.26; P=0.013). A similar trend was observed for LV
      diastolic dysfunction but did not reach statistical significance (adjusted odds
      ratio, 1.65; P=0.144). Conversely, intensive SBP control was not significantly
      associated with reduced risk of silent brain infarcts and white matter
      hyperintensity volume compared with less intensive control. CONCLUSIONS: Compared
      with less intensive control, intensive SBP control may have a stronger beneficial
      effect on cardiac than cerebral subclinical disease.

PMID- 28757487
TI  - Deformities of Nature: Sleepwalking and Non-Conscious States of Mind in Late
      Eighteenth-Century Britain.
AB  - This article examines the didactic appropriation of sleepwalking reports in late
      eighteenth-century Britain in pedagogical treatises, conduct books, and
      children's literature. It examines how and why reports of sleepwalkers were used
      to edify young minds and in so doing traces a critical shift in understandings of
      sleepwalkers, which were transformed from preternatural wonders to deformities of
      nature that exemplified the dangerous consequences of irrational, unregulated
      bodies and minds. This new role was predicated on new medical and philosophical
      understandings of sleepwalking and on the prioritisation of developmental
      psychology by pedagogues and philosophers.

PMID- 28757488
TI  - The Greatest Metaphor Ever Mixed: Gold in the British Bible, 1750-1850.
AB  - Given the frequency of negative references to gold in British allusions to filthy
      lucre, it emerges as an historical puzzle that Britons resorted to biblical
      metaphors of gold so often in describing heaven and their aspiration to be
      purified in God's crucible. This article provides evidence for the prominence of
      these two metaphors in British religious and secular discourse between 1750 and
      1850, and argues that Britons tried to resolve the resulting tensions by
      celebrating their uniquely abstract valuation of gold, in contrast to less
      "civilized" connotations of gold in Catholic and non-Christian cultures.

PMID- 28757489
TI  - The Metaphysics of Morris R. Cohen: From Realism to Objective Relativism.
AB  - Morris Cohen is mainly remembered as a philosopher of history and law, a friend
      of jurists (Oliver Wendell Holmes, Felix Frankfurter), and a teacher of more
      prominent philosophers (e.g., Ernest Nagel, Paul Weiss, Morton White). But his
      unique position as a student of the work of Russell and Peirce led him to make a
      distinctive contribution to the debate over realism in in the 1910s. Largely
      ignored and completely uncited, his early papers formulated what would later be
      called "objective relativism," influencing the later work of Columbia naturalism,
      hence American philosophy, from the 1940s to the 1960s.

PMID- 28757490
TI  - The Philosophical Genealogy of Taylor's Social Imaginaries: A Complex History of
      Ideas and Predecessors.
AB  - The deepest sources of Charles Taylor's use of the concept "social imaginaries"
      are often related to political philosophy or social anthropology (Anderson,
      Castoriadis). The purpose of this article is to show that they also form part of
      Taylor's struggle to overcome the epistemological construal in modern philosophy
      and culture. Taylor locates the concept "social imaginaries" in the Kantian
      tradition, identifying their role to that of transcendental schemes. However,
      there remains a central difference between Kant's transcendental schemes and
      Taylor's social imaginaries. To elucidate that difference, this article will
      track the philosophical genealogy of Taylor's concept of "social imaginaries" in
      three steps.

PMID- 28757493
TI  - Testing Drugs and Trying Cures: Experiment and Medicine in Medieval and Early
      Modern Europe.
AB  - This article examines traditions of testing drugs (as substances) and trying
      cures (on patients) in medieval and early modern Europe. It argues that the
      history of drug testing needs to be a more central story to overall histories of
      scientific experiment. The practice of conducting thoughtful-and sometimes
      contrived-tests on drugs has a rich and varied tradition dating back to
      antiquity, which expanded in the Middle Ages and early modern period. Learned
      physicians paired text-based knowledge (reason) with hands-on testing (experience
      or experiment) in order to make claims about drugs' properties or effects on
      humans. Lay practitioners similarly used hands-on testing to gain knowledge of
      pharmaceutical effects. Although drug testing practices expanded in scale,
      actors, and sites, therpublished a work extolling the virtues of drugs froe was
      significant continuity from the Middle Ages to the eighteenth century.

PMID- 28757494
TI  - Determining a Drug's Properties: Medieval Experimental Protocols.
AB  - Among Galenic texts attracting attention circa 1300 was De complexionibus, which
      described a crude protocol for determining the qualitative character and
      intensity of any given medicine. This caught the attention of physicians at
      Montpellier, where three generations of writers made it into a carefully
      structured test procedure for identifying by a via experimenti the nature of a
      drug's effect on healthful function: they introduced a null point as the referent
      for their measurements, identified a range of contingent factors that had to be
      controlled for, and devised ways to standardize the sample being tested. Their
      protocol was certainly designed to be used, but in practice they seemed to have
      preferred an alternative via rationis that inferred the effect of a medicine from
      sensory attributes like taste and color, acknowledging that taste tests were
      coarser and less certain than a structured experimental procedure, but were
      easier and quicker to perform than the elaborate alternative.

PMID- 28757495
TI  - The Live Chicken Treatment for Buboes: Trying a Plague Cure in Medieval and Early
      Modern Europe.
AB  - This article traces a seven-hundred-year history of one puzzling treatment for
      plague buboes that used the rumps of chickens to draw out the bubo's poisons. It
      traces the origin of the recipe to Avicenna's Canon and explores how medieval and
      early modern physicians altered the treatment and explained its workings up to
      the early eighteenth century. Much of the analysis focuses on the variants of the
      recipe that German physicians created as they adapted or elaborated on older
      recipes. This article argues that most variations of the treatment likely
      resulted from physicians trying ideas on paper, rather than in practice, as they
      attempted to unlock the mysteries of the plague's underlying poisons. Starting in
      the sixteenth century, however, evidence suggests that practice began to play an
      important role in the adaptation and interpretation of the "live chicken"
      recipes.

PMID- 28757496
TI  - Pharmacy, Testing, and the Language of Truth in Renaissance Italy.
AB  - This article examines the role of testing and innovation in sixteenthcentury
      Italian pharmacy. I argue that apothecaries were less concerned with testing
      drugs for efficacy or creating novel products than with reactivating an older
      Mediterranean pharmacological tradition and studying the materials on which it
      relied. Their practice was not driven by radical experimentation but by a
      "culture of tweaking"-of minute operational changes to existing recipes and
      accommodation of their textual variants-which was rooted in the guild economy
      fostering incremental over radical innovation and in a humanist reevaluation of
      past autorities. Workshop practice was also increasingly driven by a new ideal of
      staying true to nature fostered by the period's botanical renaissance. This led
      to an emphasis on ingredients over processes in the shop, and found clearest
      expression in the elaboration of a taxonomic "language of truth" that helped
      apothecaries discern between authentic and inauthentic materia medica and harness
      their sincerity in lieu of testing effectiveness.

PMID- 28757497
TI  - On Anecdote and Antidotes: Poison Trials in Sixteenth-Century Europe.
AB  - This article describes the use of poison trials, in which an animal or a
      condemned criminal was poisoned, to test antidotes in sixteenth-century Europe.
      In contrast to most drug testing in medieval and early modern Europe, which was
      gathered in the normal course of therapeutic experience, the poison trial was a
      contrived, deliberate event. I argue that poison trials had an important function
      in both medical testing and medical writing in the period between 1524-1580.
      While poison trials dated back to antiquity, they tended to be described in
      medieval texts as theoretical possibilities rather than empirical tests that had
      already occurred. In contrast, early modern physicians conducted poison trials
      and described them as anecdotes in medical texts. Although physicians did not
      explicitly separate poison trials from evidence gathered in the course of regular
      therapeutic experience, they did imbue the outcome of poison trials with
      considerable epistemological weight.

PMID- 28757498
TI  - Iatrochemistry and the Evaluation of Mineral Waters in France, 1600-1750.
AB  - Existing literature on mineral springs in early modern France suggests that
      composition played a minor role in the evaluation of those springs. In fact it
      played a major role from at least the beginning of the seventeenth century.
      Composition was studied by a wide range of actors, from physicians in the
      provinces to chemists at the Paris Academy of Science, with a view to
      establishing the efficacy of particular springs against particular diseases.
      Iatrochemistry played a complex role in these evaluations. Followers of
      Paracelsus and van Helmont were among the first to perform chemical analyses on
      mineral waters. But there were physicians who studied composition without
      chemistry, or who used chemistry while opposing iatrochemistry. Conversely, there
      were iatrochemists who used chemistry to study mineral waters but not to evaluate
      them, and there were many chemists who gave at least as much weight to clinical
      experience as they did to composition.

PMID- 28757499
TI  - Experimental Clinical Medicine and Drug Action in Mid-Seventeenth-Century Leiden.
AB  - Leiden University boasted one of the most popular and influential medical schools
      of the mid-seventeenth century, drawing hundreds of students from across Europe.
      These students participated in the revival of frequent clinical instruction,
      anatomical and chymical experiments, and even tests of supposed disease-causing
      substances and remedies on living animals and humans. Comparing records of cases
      from the hospital clinic with the professors' treatises and student-authored
      disputations shows that old and new theories of disease and drug action were
      hotly contested and often tested, including the claims of the leading professors
      at the school. Though notable exemplars of their work received sharp criticism
      and rejection from contemporaries and subsequent generations, Leiden students and
      professors united chymistry, postmortem autopsy, anatomical experiments, and
      clinical tests, often aiming at discovery. They enacted one, perhaps ephemeral,
      instance of experimental, clinical medicine well before its putative modern
      birth.

PMID- 28757500
TI  - Testing Drugs and Attesting Cures: Pharmaceutical Monopolies and Military
      Contracts in Eighteenth-Century France.
AB  - This article explores the role of testing in the allocation of royal monopoly
      privileges for drugs in eighteenth-century France by following the multi
      generational fortunes of a single "secret remedy" from 1713 to 1776: the poudre
      febrifuge of the Chevalier de Guiller. On at least five occasions, this drug was
      tested on patients in order to decide whether it should be protected by a
      privilege and whether or not its vendors should be awarded lucrative contracts to
      supply it in bulk to the French military. Although efforts were made early in the
      century to test the drug through large-scale hospital trials and to relegate
      privilege granting to a bureaucratic commission, the case of the poudre febrifuge
      instead suggests that military expediency and relatively small-scale trials
      administered personally by royal practitioners remained decisive in determining
      whether or not a drug received a monopoly privilege or a military contract.

PMID- 28757501
TI  - Playing God: Testing, Modeling, and Imitating Blood Miracles in Eighteenth
      Century Europe.
AB  - In the late Middle Ages, rumors began to spread throughout Europe regarding blood
      miracles associated with the relics of martyrs. Centuries-old blood, pulverized
      or solidified and black in color, was said to return to its original bright red
      color, or else to liquefy or bubble under certain circumstances or on certain
      dates in the liturgical calendar. With the Reformation, in Protestant countries
      most of these relics were either destroyed or forgotten. In Catholic countries,
      on the contrary, blood miracles multiplied, reaching a peak between the
      seventeenth and eighteenth centuries. This article reconstructs the debate that
      sprang up in eighteenth-century Europe over the blood of Saint Januarius and the
      attempts made to disprove its miraculous properties, often not in written works,
      but by staging highly theatrical demonstrations. It examines the way in which,
      with phenomena as complex as miracles, the activities of testing alleged facts,
      creating elucidative models, and staging imitations intertwined over the
      centuries, often overlapping and becoming confused.

PMID- 28757502
TI  - Therapeutic Proofs and Medical Truths: The Enduring Legacy of Early Modern Drug
      Trials.

PMID- 28757504
TI  - Popular Medicine in America 1800-1900.

PMID- 28757505
TI  - The Osler Library Prints Collection.

PMID- 28757507
TI  - Analysis of body mass changes in the Black-Headed Gull (Larus ridibundus) during
      the winter.
AB  - During the autumn migration of many waterfowls, body mass is lowest upon arrival
      at the wintering area and gradually increases during the winter. Consequently,
      body mass is highest before the spring migration. We studied the pattern of body
      mass changes in the Black-Headed Gull (Larus ridibundus) from December 2010 to
      December 2016 in the Shinhama area of Chiba, Japan. Based on 327 captured
      animals, body mass increased during the wintering period, but tended to decrease
      before migration. In 2014-2016, a muscle mass reduction in females was observed,
      explaining the change in body mass. However, the observed weight loss may be
      caused by many factors, which may be related to the migratory ecology of the
      regional population.

PMID- 28757509
TI  - Diverse distribution of tyrosine receptor kinase B isoforms in rat multiple
      tissues.
AB  - Tyrosine receptor kinase B (TrkB), a receptor for brain-derived neurotrophic
      factor and neurotrophin-3, includes the alternatively spliced three isoforms
      specifically in rats. Each isoform, full length TrkB (TrkB FL), truncated TrkB
      type-1 (TrkB T1) and type-2 (TrkB T2), seems to mediate diverse cellular
      function. Some studies suggest that TrkB plays a key role in both neural and non
      neural systems. In the present study, we examined mRNA and protein expression
      profile of three TrkB isoforms in normal adult rat multiple tissues. TrkB FL mRNA
      and protein were both highly expressed exclusively in brain. While TrkB T1 mRNA
      was highly expressed exclusively in brain, glycosylated TrkB T1 protein was
      expressed in brain and heart. TrkB T2 mRNA level in brain was the highest. In
      brain, TrkB FL mRNA expression was higher in cerebral cortex, but lower in
      brainstem. TrkB T1 mRNA expression was higher in hypothalamus, but lower in
      cerebellum. TrkB T2 mRNA expression was higher in cerebral cortex and cerebellum,
      but lower in brainstem. The present study for the first time clarified diverse
      distribution of three TrkB isoforms in rat multiple tissues and could serve as a
      useful resource for understanding the physiology and pathophysiology of mammals
      including human via comparing the expression pattern of TrkB isoforms.

PMID- 28757508
TI  - In vitro synergistic activities of cefazolin and nisin A against mastitis
      pathogens.
AB  - First-generation cephalosporins such as cefazolin (CEZ) have been widely used for
      mastitis treatment in dairy cattle. However, the use of antibiotics results in
      the presence of antibiotic residues in milk, which is used for human consumption.
      Nisin A, a bacteriocin produced by Lactococcus lactis, has been used as a broad
      spectrum food preservative for over 50 years. Therefore, a combination of CEZ and
      nisin A might provide an extended activity spectrum against mastitis pathogens
      and reduce the antibiotic dose for mastitis treatment. This study aimed to
      evaluate the combined effect of CEZ and nisin A against mastitis pathogens using
      the checkerboard and time-kill assays. In the checkerboard assay, the CEZ-nisin A
      combination exhibited a synergistic effect against Staphylococcus aureus
      (n=20/20) and Enterococcus faecalis (n=13/18), and meanwhile exhibited a mostly
      additive effect against Staphylococcus intermedius (n=12/20), Streptococcus
      agalactiae (n=10/10), Streptococcus dysgalactiae (n=18/18), and Escherichia coli
      (n=14/18). There were no indifferent or antagonistic effects between CEZ and
      nisin A. In the time-kill assay, the CEZ-nisin A combination at 0.5 * or 1 *
      minimum inhibitory concentration exhibited synergistic reduction of bacterial
      growth by over 3 log10 colony forming units per ml relative to that observed with
      either antimicrobial substance alone. These results suggest that the CEZ-nisin A
      combination can be used for developing an intramammary infusion for mastitis
      treatment, with lower antibiotic concentrations than normal.

PMID- 28757510
TI  - RNA design using simulated SHAPE data.
AB  - It has long been established that in addition to being involved in protein
      translation, RNA plays essential roles in numerous other cellular processes,
      including gene regulation and DNA replication. Such roles are known to be
      dictated by higher-order structures of RNA molecules. It is therefore of prime
      importance to find an RNA sequence that can fold to acquire a particular function
      that is desirable for use in pharmaceuticals and basic research. The challenge of
      finding an RNA sequence for a given structure is known as the RNA design problem.
      Although there are several algorithms to solve this problem, they mainly consider
      hard constraints, such as minimum free energy, to evaluate the predicted
      sequences. Recently, SHAPE data has emerged as a new soft constraint for RNA
      secondary structure prediction. To take advantage of this new experimental
      constraint, we report here a new method for accurate design of RNA sequences
      based on their secondary structures using SHAPE data as pseudo-free energy. We
      then compare our algorithm with four others: INFO-RNA, ERD, MODENA and RNAifold
      2.0. Our algorithm precisely predicts 26 out of 29 new sequences for the
      structures extracted from the Rfam dataset, while the other four algorithms
      predict no more than 22 out of 29. The proposed algorithm is comparable to the
      above algorithms on RNA-SSD datasets, where they can predict up to 33 appropriate
      sequences for RNA secondary structures out of 34.

PMID- 28757512
TI  - Sulfonyl phosphonic 1,4-dithia-7-azaspiro[4,4]nonane derivatives as matrix
      metalloproteinase inhibitors: Synthesis, a docking study, and biological
      evaluation.
AB  - A series of novel sulfonyl phosphonic 1,4-dithia-7-azaspiro[4,4]nonane
      derivatives were designed, synthesized, and assayed for their activity against
      matrix metalloproteinase-2 (MMP-2). Results indicated that all of the compounds
      exhibited moderate inhibitory activity against MMP-2 compared to LY52 (the
      control) (IC50 = 0.95 +/- 0.09 uM). Several selected compounds were also examined
      for their antiproliferative activity against SKOV3, HL60, and A549 cells.
      Notably, all of the tested compounds had slightly lower antiproliferative
      activity against SKOV3 cells than that of LY52. Compound 6d displayed the
      greatest inhibitory activity in an enzymatic assay and a cell-based assay, which
      means that this compound is a good candidate for further development of
      phosphonate-based MMP inhibitors.

PMID- 28757511
TI  - Use of animal models for the imaging and quantification of angiogenesis.
AB  - Angiogenesis is the process of developing new blood vessels from the original
      vascular network; it is necessary for normal physiological processes, such as
      embryonic development and wound healing. Angiogenesis is also involved in
      pathological events, including myocardial ischemia and tumor growth. To
      investigate the molecular mechanisms of this important process, a variety of
      methods and models are employed. These strategies can also be used to provide
      insight into the etiology of angiogenesis-related diseases, thereby contributing
      to the development of new diagnostics and treatments. Commonly used animal models
      include the chorioallantoic membrane and yolk sac membrane of chick embryos, the
      mouse retina and aortic ring, and angiogenesis reactors implanted into mice.
      These animal models have been instrumental in the study of the angiogenic
      process. For example, the chorioallantoic membrane undergoes robust angiogenesis
      during the development of chick embryos, and, because its surface is easily
      accessible, this membrane provides a convenient model for experimentation. Here,
      we discuss the methods that employ animal models for the imaging and
      quantification of angiogenesis. In addition, we propose potential novel
      directions for future investigations in this area.

PMID- 28757513
TI  - Validation of a sheet-shaped body vibrometer for screening of obstructive sleep
      apnea.
AB  - We assessed the validity of using a sheet-shaped body vibrometer (SBV) as a
      portable monitoring device for obstructive sleep apnea (OSA) screening. Seventy
      consecutive patients with suspected OSA underwent simultaneous in-laboratory
      polysomnography (PSG) and SBV. We evaluated the screening accuracy of the
      respiratory event index (REI) obtained with the SBV, using the REI based on
      either the estimated total sleep time (REI_eTST) or time in bed (REI_TIB); these
      were compared to the apnea-hypopnea index (AHI) obtained via PSG. Bland-Altman
      plots indicated that the mean difference between REI_eTST and AHI was lower than
      that between REI_TIB and AHI (1.2 +/- 19.8 vs. 6.5 +/- 16.8). For AHI >= 15, the
      sensitivity and specificity at an optimal REI_eTST of 17.0 were 90.9% and 76.9%,
      whereas those at an optimal REI_TIB of 15.9 were 86.4% and 80.8%, respectively;
      moreover, for AHI >= 30, these values at an optimal REI_eTST of 26.0 were 89.5%
      and 88.2%, whereas those at an optimal REI_TIB of 23.8 were 84.2% and 92.2%,
      respectively. The optimal cutoff values of REIs for AHI of >= 5 were markedly
      different from those for AHI obtained via PSG (REI_eTST, 14.9; REI_TIB, 15.0),
      but close to those for AHI of >= 15; both had good sensitivities and
      specificities. REIs obtained via SBV performed well in moderate-to-severe, but
      not mild, OSA screening; REI_eTST showed a slightly higher sensitivity and a
      relatively closer value to the AHI obtained via PSG when compared to REI_TIB. We
      consider the SBV less acceptable for screening mild cases than more severe cases.

PMID- 28757514
TI  - N-acetyl glucosamine and proteoglycan containing supplement improves the
      locomotor functions of subjects with knee pain.
AB  - The aim of this study was to investigate the effect of N-acetyl glucosamine and
      proteoglycan-containing supplement (NGPS) on knee pain and locomotor functions in
      middle-aged and elderly persons with knee pain. An open trial was conducted on 19
      subjects suffering from knee pain. The subjects, aged (55.6 +/- 6.9) years, were
      given the NGPS tablets, which they must take 3 times per day, that contain 526.5
      mg of N-acetyl glucosamine (GlcNAc) and 33.6 mg of proteoglycan for 12 weeks.
      Subjective pain was evaluated using the Visual Analog Scale (VAS), while the
      function of the knee with regard to daily operation was evaluated using the
      Japanese Knee Osteoarthritis Score (JKOM). Walking, stair-climbing and swelling
      were evaluated using the Japanese Orthopedic Association Score (JOA). These items
      were evaluated at a baseline, and after 4, 8, and 12 weeks of NGPS treatment. The
      VAS scores at 8 (p = 0.004) and 12 (p < 0.001) weeks were significantly lower
      than that at the baseline. The JKOM total score was significantly lower at 8 and
      12 weeks (p = 0.001) than that at the baseline. The JOA score in the more painful
      side of the leg was significantly higher at 12 weeks (p = 0.002) than that at the
      baseline. The present study reveals that intake of NGPS is effective for
      relieving knee pain and improving knee function when walking or climbing stairs,
      swelling and bending or stretching.

PMID- 28757515
TI  - Association between type 1 diabetes mellitus and risk of epilepsy: A meta
      analysis of observational studies.
AB  - A potential association between type 1 diabetes mellitus and subsequent epilepsy
      emerged in recent studies. This study aimed to evaluate the possible relationship
      between type 1 diabetes mellitus and epilepsy using meta-analysis. Pubmed, ISI
      Web of Knowledge, Embase and Cochrane Library were searched for potential studies
      of the association between type 1 diabetes mellitus and epilepsy from inception
      to February 1, 2017. Two investigators independently screened studies for
      inclusion and extracted related data; discrepancies were solved by consensus.
      Random effects model of Hazard Ratio (HR) was used to estimate the strength of
      association. We identified 13 papers from potentially relevant articles of which
      3 cohort studies met the inclusion criteria. Random effects meta-analysis showed
      that type 1 diabetes mellitus was associated with an increased risk of epilepsy
      with HR = 3.29 (95% CI: 2.61-4.14; I2 = 0, p = 0.689). Similar results were
      observed in type 1 diabetes mellitus patents younger than 18-years-old with HR =
      2.96 (95% CI: 2.28-3.84; I2 = 0, p = 0.571). Meta-analysis of 2 studies that
      adjusted for potential confounders yielded an increased risk of epilepsy with HR
      = 2.89 (95% CI: 2.26-3.70; I2 = 0, p = 0.831). The meta-analysis indicates that
      type 1 diabetes mellitus is associated with a statistically significant increased
      risk for epilepsy compared to those without type 1 diabetes mellitus.

PMID- 28757516
TI  - Combination of triple biomarkers AFP, AFP-L3, and PIVAKII for early detection of
      hepatocellular carcinoma in China: Expectation.
AB  - Hepatocellular carcinoma (HCC) remains a severe health threat in China. Early
      tumor detection is crucial for improving the prognosis of patients. Currently,
      ultrasound plus biomarker alpha fetoprotein (AFP) is recommended by Chinese Liver
      Cancer Diagnosis and Treatment Guidelines in China. However, most HCC continues
      to be diagnosed beyond an early stage due to insufficient sensitivity and
      specificity of current surveillance tools, highlighting the need for more
      accurate biomarkers to improve early HCC detection. In Japan, ultrasound plus
      triple biomarkers AFP, Lens culinaris agglutinin-reactive fraction of AFP (AFP
      L3), and prothrombin induced by vitamin K absence II (PIVKA II) has been
      routinely used for HCC surveillance and achieved increased early HCC detection
      rate. Very recently, the assay of triple biomarkers AFP, AFP-L3, and PIVKA II
      using MUTASWako i30 immuno-analyzer was brought into China. The prospect of the
      modality of ultrasound plus triple biomarkers for early HCC detection in China is
      expected in the future.

PMID- 28757518
TI  - Pathological Quantification of Carotid Artery Plaque Instability in Patients
      Undergoing Carotid Endarterectomy.
AB  - BACKGROUND: Unstable atherosclerotic carotid plaques cause cerebral thromboemboli
      and ischemic events. However, this instability has not been pathologically
      quantified, so we sought to quantify it in patients undergoing carotid
      endarterectomy (CEA).Methods and Results:Carotid plaques were collected during
      CEA from 67 symptomatic and 15 asymptomatic patients between May 2015 and August
      2016. The specimens were stained with hematoxylin-eosin and elastica-Masson.
      Immunohistochemistry was performed using an endothelial-specific antibody to
      CD31, CD34 and PDGFRbeta. The histopathological characteristics of the plaques
      were studied. By multiple-variable logistic regression analysis, plaque
      instability correlated with the presence of plaque rupture [odds ratio (OR),
      9.75; P=0.013], minimum fibrous cap thickness (OR per 10 MUm 0.70; P=0.025),
      presence of microcalcifications in the fibrous cap (OR 7.82; P=0.022) and
      intraplaque microvessels (OR 1.91; P=0.043). Receiver-operating characteristics
      analyses showed that these factors combined into a single score diagnosed
      symptomatic carotid plaques in patients with carotid artery stenosis with a high
      level of accuracy (area under the curve 0.92; 95% confidence interval 0.85-0.99
      vs. asymptomatic). CONCLUSIONS: This analysis of carotid plaque instability
      strongly suggested that the diagnostic scoring of carotid plaque instability
      improves the understanding and treatment of carotid artery disease in patients
      undergoing CEA.

PMID- 28757517
TI  - Reproducible insulin secretion from isolated rat pancreas preparations using an
      organ bath.
AB  - Diabetes mellitus is a lifestyle-related disease that is characterized by
      inappropriate or diminished insulin secretion. Ex vivo pharmacological studies of
      hypoglycemic agents are often conducted using perfused pancreatic preparations.
      Pancreas preparations for organ bath experiments do not require cannulation and
      are therefore less complex than isolated perfused pancreas preparations. However,
      previous research has generated almost no data on insulin secretion from pancreas
      preparations using organ bath preparations. The purpose of this study was to
      investigate the applicability of isolated rat pancreas preparations using the
      organ bath technique in the quantitative analysis of insulin secretion from beta
      cells. We found that insulin secretion significantly declined during incubation
      in the organ bath, whereas it was maintained in the presence of 1 uM GLP-1.
      Conversely, amylase secretion exhibited a modest increase during incubation and
      was not altered in the presence of GLP-1. These results demonstrate that the
      pancreatic organ bath preparation is a sensitive and reproducible method for the
      ex vivo assessment of the pharmacological properties of hypoglycemic agents.

PMID- 28757519
TI  - Protruding In-Stent Mass After Bioresorbable Polymer Sirolimus-Eluting Stent - Ex
      Vivo Intravascular Imaging and Histopathology.

PMID- 28757520
TI  - Role of Routine Follow-up Coronary Angiography After Percutaneous Coronary
      Intervention - Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Prior studies have shown that routine follow-up coronary angiography
      (CAG) following percutaneous coronary intervention (PCI) increases the incidence
      of revascularization without a clear reduction in major adverse clinical events.
      However, none of these prior studies were adequately powered to evaluate hard
      clinical endpoints such as myocardial infarction (MI) or death and thus the
      clinical utility of such practice remains to be determined.Methods and Results:We
      conducted a systematic review and meta-analysis of randomized trials that
      compared clinical outcomes after PCI between patients who underwent routine
      follow-up CAG and those who only had clinical follow-up. Five randomized trials,
      totaling 4,584 patients met our inclusion criteria, including studies that used
      sub-randomization and ones that assigned consecutive patients per study protocol.
      Our results showed that routine follow-up CAG was associated with a lower rate of
      MI (odds ratio [OR] 0.65; 95% confidence interval [CI] 0.46-0.91; P=0.01) without
      reduction in all-cause mortality (OR 0.87; 95% CI 0.59-1.28; P=0.48), and a
      higher rate of target lesion revascularization (OR 1.73; 95% CI 1.42-2.11;
      P<0.001). CONCLUSIONS: Our meta-analysis demonstrated that routine follow-up CAG
      after PCI was associated with a higher rate of revascularization, but also with a
      reduction in the rate of subsequent MI. Further studies investigating the
      potential role of routine follow-up angiography may be warranted.

PMID- 28757521
TI  - Retrospective investigation of cardiopulmonary resuscitation outcome in 146
      exotic animals.
AB  - The outcomes of cardiopulmonary resuscitation (CPR) were retrospectively
      evaluated in 146 exotic animals including 20 pet birds, 47 rabbits, 34 hamsters,
      18 ferrets, 7 turtles and 20 other small mammals in cardiopulmonary arrest (CPA)
      at presentation or during hospitalization at an animal clinic. The rates of
      return of spontaneous circulation, survival after CPR and discharge were 9.3, 2.3
      and 1.2%, respectively. The mean success rate of CPR in animals included in this
      study was lower than those previously reported in dogs and cats. This might have
      been because of the challenges in effective chest compression, airway management
      and monitoring as well as establishment of intravenous catheterization route in
      exotic animals.

PMID- 28757522
TI  - Cattle with the BoLA class II DRB3*0902 allele have significantly lower bovine
      leukemia proviral loads.
AB  - The bovine MHC (BoLA) class II DRB3 alleles are associated with polyclonal
      expansion of lymphocytes caused by bovine leukemia virus (BLV) infection in
      cattle. To examine whether the DRB3*0902 allele, one of the resistance-associated
      alleles, is associated with the proviral load, we measured BLV proviral load of
      BLV-infected cattle and clarified their DRB3 alleles. Fifty-seven animals with
      DRB3*0902 were identified out of 835 BLV-infected cattle and had significantly
      lower proviral load (P<0.000001) compared with the rest of the infected animals,
      in both Japanese Black and Holstein cattle. This result strongly indicates that
      the BoLA class II DRA/DRB3*0902 molecule plays an important immunological role in
      suppressing viral replication, resulting in resistance to the disease
      progression.

PMID- 28757523
TI  - Operative techniques of percutaneous endoscopic mini-hemilaminectomy using a
      uniportal approach in dogs.
AB  - The present study aimed to investigate the technical feasibility of percutaneous
      endoscopic mini-hemilaminectomy via a uniportal approach, and to evaluate the
      possibility of decompression and endoscopic examination of the thoracic and
      lumbar spinal canals in small dogs during such procedures. Fresh canine cadavers
      of mixed-breed dogs (n=7) were used in this study. Following injection of a
      barium and agarose mixture (BA-gel) to stimulate intervertebral disc herniation,
      percutaneous endoscopic mini-hemilaminectomy was performed using a lateral
      approach to the thoracic and lumbar vertebrae. BA-gel was removed to decompress
      the spinal cord using an elevator and rongeurs after mini-hemilaminectomy. Pre
      and post-operative computed tomography (CT) scans were obtained to evaluate
      surgical outcomes. Intra-operative complications, incision length, and procedure
      time were recorded. All procedures were completed with clear visualization of the
      spinal cord and floor of the spinal canal. The mean total operating time was
      58.00 +/- 18.06 min. Lengths of incision were under 1 cm in all dogs. Intra
      operative complications included iatrogenic nerve root injuries caused by the
      micro-rongeur in two dogs. CT imaging revealed that removal of BA-gel resulted in
      sufficient spinal cord decompression. Our findings indicated that percutaneous
      endoscopic thoracolumbar mini-hemilaminectomy is feasible for spinal cord
      decompression and allows for adequate observation of the spinal canal. Thus, this
      technique may be an alternative surgical option for treatment of thoracolumbar
      disk disease in dogs.

PMID- 28757524
TI  - A novel method of gene transduction to the murine endometrium using in vivo
      electroporation.
AB  - To investigate the molecular pathways involved in successful embryo implantation
      in mammals, we developed a novel method for gene transduction into the murine
      endometrium using in vivo electroporation. Plasmid DNA with an enhanced green
      fluorescence protein (EGFP) gene was injected into the uterine cavity of non
      pregnant female mice, and electrical pulses were subsequently applied to the
      uterine horn using plate electrodes. EGFP expression was found only in the
      uterine luminal epithelium (LE), but not in the stroma. EGFP fluorescence in the
      LE was limited to the site where the positive side of the electrodes was placed
      during electric stimulation. These results demonstrated that our novel method
      enabled us to transduce a gene into a desired location of the murine uterus.

PMID- 28757525
TI  - Traumatic pericarditis caused by a bamboo twig in captive waterbuck (Kobus
      ellipsiprymnus).
AB  - A 19-year-old captive male waterbuck (Kobus ellipsiprymnus) exhibited traumatic
      pericarditis at necropsy. The animal weighed 182 kg at necropsy and revealed no
      remarkable findings in external observation. Severe pericardial adhesions with
      fibrosis, hepato-diaphragmatic adhesions, straw-colored ascites and
      hepatosplenomegaly were observed upon examining the internal organs. Perforations
      made by a 12-cm-long sharp-ended bamboo twig were detected in the reticulum,
      diaphragm, pericardium, lung and liver. Trueperella pyogenes was identified in
      pericardial fluid. To our knowledge, this is the first documented case of
      traumatic reticulopericarditis caused by a sharp-ended bamboo twig in a captive
      waterbuck.

PMID- 28757526
TI  - Morphologically abnormal beaks observed in chickens that were beak-trimmed at
      young ages.
AB  - A survey of beak morphological abnormalities was performed on 6,201 chickens (egg
      laying hens and chickens for meat production belonging to 25 flocks) brought to a
      poultry processing plant. The observed abnormalities varied among flocks with
      occurrence rates ranging from 0.48 to 46.67%. The occurrence was high in flocks
      subjected to beak trimming and varied significantly according to chicken breed,
      with the highest rates of abnormalities in a certain chicken breed. The most
      widely observed abnormalities were: 1) uneven growth of the upper and lower
      mandibles, mostly with elongation of the lower mandible (accounting for 64.8% of
      all abnormalities); 2) misalignment of the upper and lower mandibles, causing
      lateral deviation or crossing (16.3%); 3) sharp or jagged deformities of the
      mandible tips (10.1%); 4) permanent open beak, a deformity in which the beak did
      not close completely even when closed (5.8%); and 5) formation of tubercular
      swellings at the tips of the upper or lower mandibles (3.1%). This is the first
      report on the occurrence of beak abnormalities in beak-trimmed poultry in Japan.

PMID- 28757527
TI  - RAD51 maintains chromosome integrity and mitochondrial distribution during
      porcine oocyte maturation in vitro.
AB  - DNA repair protein RAD51 homolog 1 (RAD51) plays a central role in homologous
      recombination (HR) repair of DNA breaks. HR depends on the formation of a RAD51
      recombinase filament that facilitates strand invasion. However, the role of RAD51
      during porcine oocyte maturation is unknown. The objective of this study was to
      investigate the expression and function of RAD51 during porcine oocyte maturation
      in vitro. RAD51 was mainly localized to the nucleus at the germinal vesicle (GV)
      stage, and was widely distributed in the cytoplasm between the GV breakdown
      (GVBD) and metaphase II stage. DNA damage induced by etoposide was accompanied by
      the formation of RAD51 foci that were colocalized with gammaH2AX. Inhibition of
      RAD51 increased DNA damage and induced metaphase I arrest along with spindle
      defects, chromosomal misalignment, and abnormal spindle assembly checkpoint (SAC)
      activity. Inhibition of RAD51 also increased ROS levels and led to an abnormal
      mitochondrial distribution. Our results indicate that RAD51 plays a critical role
      in maintaining chromosome integrity and mitochondrial activity during porcine
      oocyte maturation.

PMID- 28757528
TI  - Vitamin D Insufficiency Predicts Elevated Levels of Complement 3 Independent of
      Insulin Resistance and BMI.
AB  - This study was to determine serum 25-hydroxyvitamin D (25(OH)D), the complement 3
      (C3), and C-reactive protein (CRP) levels, and their association with the risk of
      insulin resistance (IR). A case-control study was carried out among 134
      participants with body mass index (BMI) >=30 kg/m2 and BMI=18.5-24.99 kg/m2.
      Anthropometric and body composition indicators were measured. Serum levels of C3,
      CRP, 25(OH)D, insulin, and glucose were also measured. IR was assessed by the
      homeostasis model assessment (HOMA-IR). C3, CRP, insulin, and HOMA-IR levels were
      higher in participants with obesity than that of controls (p<0.001). After
      adjustment for the potential confounders, anthropometric and body composition
      indicators were correlated positively with C3 (p<0.001), and negatively with
      25(OH)D (p<0.05). C3, and 25(OH)D were correlated with HOMA-IR (r=0.350; r=
      0.212; p<0.05). In logistic regression analyses, C3 and CRP were significantly
      related to increased odds of IR among participants with obesity as compared to
      controls after progressively adjusting for the potential confounders (p<0.001),
      whereas 25(OH)D was negatively, but insignificantly, related to decreased odds of
      IR among participants with obesity (p>0.05). C3 was associated positively with
      25(OH)D insufficiency/deficiency independent of HOMA-IR and/or BMI (beta=0.183,
      p<0.05). Obesity is associated with elevated levels of proinflammatory biomarkers
      and IR. 25(OH)D insufficiency/deficiency was associated with C3 regardless of
      HOMA-IR or BMI, which could in turn, have a role in the augmentation of IR during
      obesity.

PMID- 28757529
TI  - Inhibition of Adipogenesis Is Involved in the Protective Effects of 1,25
      Dihydroxy Vitamin D3 on the Radiation-Injured Bone Marrow Microenvironment in
      Mice.
AB  - To explore the protective effects of 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) on
      the bone marrow microenvironment in mice after irradiation and the underlying
      molecular mechanisms, a total of 150 7-wk-old male BALB/c mice were randomly
      divided into a normal group, an irradiation (IR) group and an irradiation+1,25
      (OH)2D3 (IR+VD3) group. The mice in the IR+VD3 group were treated with 6.0 Gy
      60Cogamma rays, and 1,25-(OH)2D3 (dissolved in DMSO, 2.5 MUg/kg) was administered
      once per day from 2 d before to 8 d after irradiation. Mice in the IR group were
      treated with the same dose of gamma rays and an equal volume of DMSO.
      Subsequently, the body weights and the numbers of peripheral white blood cells
      (WBCs) were measured. Histological analysis of femur bone marrow was conducted to
      determine the proportion of adipose area as well. Finally, the expression of
      peroxisome proliferator-activated receptor-gamma (PPARgamma) in bone marrow was
      detected by immunohistochemistry. After irradiation, the percentage of adipose
      area in the bone marrow was significantly increased, and the WBC number and body
      weight were markedly reduced. Compared with irradiation alone, the co
      administration of 1,25-(OH)2D3 with irradiation markedly attenuated radiation
      induced adipogenesis in bone marrow, resulted in fewer bone marrow stromal cells
      expressing PPARgamma and enhanced the recovery of body weight and WBCs. These
      results indicate that 1,25-(OH)2D3 could accelerate the recovery of body weight
      and WBCs in irradiated mice and protect the bone marrow by inhibiting radiation
      induced adipogenesis via the down-regulation of PPARgamma expression.

PMID- 28757530
TI  - Perceived 6-n-Propylthiouracil (PROP) Bitterness Is Associated with Dietary
      Sodium Intake in Female Japanese College Students.
AB  - Despite the negative health consequences of a high sodium consumption, humans
      consume well above the recommended levels. This study examines whether or not the
      dietary intake of sodium was affected by individual variation of the perceived
      bitterness of 6-n-propylthiouracil (PROP), and examines the relationship between
      the perceived bitterness of PROP and the preferred NaCl concentration of broth.
      Female students (20-22 y old) were recruited from the university community.
      Genotypes of A49P and I296V polymorphism of the TAS2R38 bitter taste receptor
      were determined for each subject. Samples containing NaCl, PROP or broth in 5-mL
      portions were evaluated by sensory testing. The participants completed a food
      record for each diet. Our results indicate that the individuals perceiving PROP
      to be more bitter had consumed a greater amount of dietary sodium. In contrast,
      there was no significant positive correlation between an individual's perceived
      saltiness and the dietary sodium intake. Those who perceived PROP to be more
      bitter preferred a broth containing a higher concentration of NaCl. All of these
      correlations were apparent even after those subjects with TAS2R38 AI/AI
      homozygotes (PROP non-taster) had been excluded. In conclusion, the results of
      this study suggest that a factor affecting the bitter rating of PROP other than
      the AI/AI homozygotes of TAS2R38 contributes to the variation in sodium intake
      and the preference for salty food.

PMID- 28757531
TI  - Objective and Subjective Eating Speeds Are Related to Body Composition and Shape
      in Female College Students.
AB  - Eating speed reportedly relates to body composition and shape. Little is known
      about the relationship between the objectively assessed eating speed and the body
      composition and shape. This study examined relationships between eating speed as
      assessed both objectively and subjectively, and body composition and shape. The
      following variables of body composition and shape were measured in 84 female
      college students: body mass, relative body fat mass (%Fat), body mass index
      (BMI), and circumferences of the waist, abdomen and hip. After measuring the body
      composition and shape, subjects consumed a 174-kcal salmon rice ball. The
      following chewing variables were measured by observing videotape recordings of
      the subjects' faces: number of chews per bite, total number of chews, total meal
      duration, number of bites, and chewing rate. The subjects were categorized into
      three groups (fast, moderate and slow) according to their own subjective
      assessments of the actual eating speed. In objective assessments of the eating
      speed, the total number of chews and the total meal duration were significantly
      negatively correlated with the body mass, %Fat, BMI, and circumferences of the
      waist, abdomen and hip. In subjective eating-speed assessments, the body mass,
      %Fat, BMI, and circumferences of the waist, abdomen and hip were greater in the
      fast eating group than in the slow eating group. Both the objectively and
      subjectively assessed eating speeds are related to the body composition and
      shape. The present study supports that fast eating may relate to gains in body
      mass and/or fat mass.

PMID- 28757532
TI  - Dietary Polyphenol Intake Estimated by 7-Day Dietary Records among Japanese Male
      Workers: Evaluation of the Within- and Between-Individual Variation.
AB  - Polyphenol intake has been estimated in some populations; however, information
      about day-to-day and individual differences in polyphenol intake has not been
      well-evaluated. In this study, we aimed to examine within- and between-individual
      variation in polyphenol intake in Japanese male workers. First, 56 male subjects
      (aged 37.9+/-10.4 y) completed detailed 7-d dietary records (DR). We then
      calculated their total polyphenol intake using our polyphenol content database
      and the within- and between-individual variations. We also estimated the minimum
      number of days of dietary assessment required both to rank individuals within a
      group and to assess an individual's usual polyphenol intake with acceptable
      accuracy. The estimated daily total polyphenol intake was 965+/-471 mg/d, which
      was largely sourced from beverages. The day-to-day variation (CVw) for polyphenol
      intake was 43.6%, and the variation between the individuals in the population
      (CVb) for polyphenol intake was 45.9%. A 4-d DR was required to rank individuals
      within a group with high correlation coefficients (r=0.9), and a 19-d DR was
      required to assess the individual's usual polyphenol intake with 20% deviation.
      The CVw for polyphenol intake was intermediate between those of the other
      nutrients, but the CVb for polyphenol intake was largest among the nutrients.
      These results suggest that the dietary intake of polyphenols should be carefully
      estimated considering its within- and between-individual variation.

PMID- 28757533
TI  - Oral Carbonation Attenuates Feeling of Hunger and Gastric Myoelectrical Activity
      in Young Women.
AB  - We previously reported that carbonated water ingestion induced fullness and
      gastric motility. In order to determine whether such satiating effects occur
      through oral carbonic stimulation alone, we conducted modified sham-feeding (SF)
      tests (carbonated water ingestion (CW), water ingestion (W), carbonated water
      sham-feeding (CW-SF), and water sham-feeding (W-SF)), employing an equivalent
      volume and standardized temperature of carbonated and plain water, in a
      randomized crossover design. Thirteen young women began fasting at 10 p.m. on the
      previous night and were loaded with each sample (15oC, 250 mL) at 9 a.m. on
      separate days. Electrogastrography (EGG) recordings were obtained from 20 min
      before to 45 min after the loading to determine the power and frequency of the
      gastric myoelectrical activity. Appetite was assessed using visual analog scales.
      After ingestion, significantly increased fullness and decreased hunger ratings
      were observed in the CW group. After the load, transiently but significantly
      increased fullness as well as decreased hunger ratings were observed in the CW-SF
      group. The powers of normogastria (2-4 cpm) and tachygastria (4-9 cpm) showed
      significant increases in the CW and W groups, but not in the CW-SF and W-SF
      groups. The peak frequency of normogastria tended to shift toward a higher band
      in the CW group, whereas it shifted toward a lower band in the CW-SF group,
      indicating a different EGG rhythm. Our results suggest that CO2-induced oral
      stimulation is solely responsible for the feeling of satiety. Moreover, different
      gastric-contraction rhythms (slow or fast) were induced by oral carbonic
      stimulation alone and carbonated water ingestion.

PMID- 28757534
TI  - Triterpenoids Isolated from Ziziphus jujuba Enhance Glucose Uptake Activity in
      Skeletal Muscle Cells.
AB  - Jujube (Ziziphus jujuba Mill.), a traditional folk medicine and functional food
      in China and South Korea, is known for its beneficial properties, which include
      anti-cancer, anti-oxidative, and anti-obesity effects. To assess the anti
      hyperglycemic effect of jujube in this study, we investigated the glucose uptake
      promoting activity of jujube in rat L6 myotubes. After determining that the
      jujube extract induces muscle glucose uptake, we identified the following active
      compounds by bioassay-guided fractionation: betulonic acid, betulinic acid, and
      oleanonic acid. Ursonic acid, known to be present in jujube, was semi-synthesized
      from ursolic acid and also observed to enhance glucose uptake. These four
      triterpenic acids induced glucose uptake in a glucose transporter 4-dependent
      manner. Comparison experiments of jujube fruits from three countries, namely,
      China, South Korea, and Japan, revealed that Japanese jujube has a higher content
      of active triterpenoids and is the most potent enhancer of glucose uptake.

PMID- 28757535
TI  - Coffee Ingestion Suppresses Hyperglycemia in Streptozotocin-Induced Diabetic
      Mice.
AB  - Coffee consumption reduces the risk of type 2 diabetes in humans, but the
      mechanism remains unclear. In this study, we investigated the effect of coffee on
      pancreatic beta-cells in the induction of diabetes by streptozotocin (STZ)
      treatment in mice. We examined the effect of coffee, caffeine, or decaffeinated
      coffee ingestion on STZ-induced hyperglycemia. After STZ injection in Exp. 1 and
      2, serum glucose concentration and water intake in coffee ingestion (Coffee
      group) tended to be lowered or was significantly lowered compared to those in
      water ingestion (Water group) instead of coffee. In Exp. 1, the values for water
      intake and serum glucose concentration in caffeine ingestion (Caffeine group)
      were similar to those in the Water group. In Exp. 2, serum glucose concentrations
      in the decaffeinated coffee ingestion (Decaf group) tended to be lower than those
      in the Water group. Pancreatic insulin contents tended to be higher in the Coffee
      and Decaf groups than in the Water group (Exp. 1 and 2). In Exp. 3, subsequently,
      we showed that coffee ingestion also suppressed the deterioration of
      hyperglycemia in diabetic mice which had been already injected with STZ. This
      study showed that coffee ingestion prevented the development of STZ-induced
      diabetes and suppressed hyperglycemia in STZ-diabetic mice. Caffeine or
      decaffeinated coffee ingestion did not significantly suppress STZ-induced
      hyperglycemia. These results suggest that the combination of caffeine and other
      components of decaffeinated coffee are needed for the preventive effect on
      pancreatic beta-cell destruction. Coffee ingestion may contribute to the
      maintenance of pancreatic insulin contents.

PMID- 28757536
TI  - Comparison of Anti-Obesity Effect between Two Types of Syrup Containing Rare
      Sugars in Wistar Rats.
AB  - D-Allulose-containing rare sugar sweeteners have been categorized into two types,
      rare sugar syrup (RSS), consisting of 4 rare monosaccharides, and modified
      glucose syrup (MGS), rich in D-allulose, which was previously referred to D
      psicose. The anti-obesity effect of RSS and D-allulose has been already
      clarified, but that of rare monosaccharides other than D-allulose in RSS has not
      yet been well understood. Here, we investigated and compared the anti-obesity
      effect of RSS and MGS in rats. Male Wistar rats were divided into 4 dietary
      groups: a high-sucrose control diet group (S), a high-fructose corn syrup diet
      group (HFCS), an RSS diet group (RSS), and an MGS diet group (MGS). RSS
      significantly suppressed abdominal adipose tissue weight and total body fat
      accumulation in comparison to sucrose. On the other hand, MGS reduced body weight
      gain, but not abdominal fat accumulation, relative to sucrose. The weight of the
      liver and kidneys was significantly higher in the RSS and MGS groups than in the
      S and HFCS groups, but serum biochemical parameters and hepatic lipids contents
      were not significantly different among the groups. The present study shows that
      two types of D-allulose-containing rare sugar sweeteners can suppress body fat
      accumulation or weight gain in a different manner and that RSS could be used as
      more effective sweeteners in place of sucrose and HFCS to maintain healthy body
      weight.

PMID- 28757537
TI  - Knowledge Translation for Cardiovascular Disease Research and Management in
      Japan.
AB  - Knowledge translation is an essential and emerging arena in healthcare research.
      It is the process of aiding the application of research knowledge into clinical
      practice or policymaking. Individuals at all levels of the health care system,
      including patients, healthcare professionals, and policymakers, are affected by
      the gaps that exist between research evidence and practice; the process of
      knowledge translation plays a role in bridging these gaps and incorporating high
      quality clinical research into decision-making. Cardiovascular disease (CVD)
      management is a crucial area of healthcare where information gaps are known to
      exist. Although Japan has one of the lowest risks and mortality rates from CVDs,
      an increasing trend of cardiovascular incidence and changes in the risk factor
      conditions have been observed in recent years. This article provides an overview
      of knowledge translation and its importance in the cardiovascular health of the
      Japanese population, and describes the key steps of a typical knowledge
      translation strategy.

PMID- 28757539
TI  - Electrophysiological Assessment for Splinting in the Treatment of Carpal Tunnel
      Syndrome.
AB  - An electrophysiological study is commonly used to decide a therapeutic strategy
      for carpal tunnel syndrome (CTS). In this study, the electrophysiological
      parameter measurement as a prognostic indicator for CTS after wrist splinting was
      assessed to identify appropriate candidates for wrist splinting for CTS. One
      hundred and six hands in 78 patients with CTS were treated by wrist splinting,
      and three electrophysiological parameters; median distal motor latency (DML) of
      the abductor pollicis brevis (APB) muscle, median distal sensory latency (DSL) of
      the index finger, and second lumbrical-interossei latency difference (2L-INT LD);
      were statistically analyzed to compare with clinical results by Kelly's
      evaluation respectively. Clinical results were excellent in 15 hands, good in 51
      hands, fair in 19 hands, and poor in 21 hands. The recordable rate in 2L-INT LD
      (99.1%) was higher than DML (96.2%) and DSL (79.2%). Patients with DML less than
      6.5 ms, DSL less than 5.7 ms, or 2L-INT LD less than 2.5 ms had significantly
      excellent or good clinical results. The odds ratios of the DML, DSL, and the 2L
      INT LD were 7.93, 8.81, and 12.8, respectively. This study demonstrated that CTS
      patients with DML less than 6.5 ms, DSL less than 5.7 ms, or 2L-INT less than 2.5
      ms were good candidates for wrist splinting. Especially, the 2L-INT LD could be
      the most reliable indicator to predict clinical results for all grades of CTS.
      This electrophysiological information could be useful in further improvement of
      accurate diagnosis of CTS, and may help in the assessment of appropriate
      treatment for CTS with wrist splinting.

PMID- 28757538
TI  - The Roles of Hypoxia Signaling in the Pathogenesis of Cardiovascular Diseases.
AB  - The circulatory system distributes blood flow to each tissue and transports
      oxygen and nutrients. Peripheral circulation is required to maintain the
      physiological function in each tissue. Disturbance of circulation, therefore,
      decreases oxygen delivery, leading to tissue hypoxia which takes place in several
      cardiovascular disorders including atherosclerosis, pulmonary arterial
      hypertension and heart failure. While tissue hypoxia can be induced because of
      cardiovascular disorders, hypoxia signaling itself has a potential to modulate
      tissue remodeling processes or the severity of the cardiovascular disorders.
      Hypoxia inducible factor-1alpha (HIF-1alpha) and HIF-2alpha belongs to a group of
      transcription factors which mediate most of the cellular responses to hypoxia at
      a transcriptional level. We, and others, have reported that HIF-alpha signaling
      plays a critical role in the initiation or the regulation of inflammation. HIF
      alpha signaling contributes to the tissue remodeling processes; thus it has a
      potential to become a therapeutic target. Elucidation of the molecular link,
      therefore, between hypoxia signaling and tissue remodeling will greatly help us
      to understand the pathophysiology of the cardiovascular disorders. The purpose of
      this review is to give a brief overview of the current understanding about the
      function HIF-alpha in inflammation processes especially by focusing on its roles
      in macrophages. In addition, the pathophysiological roles of hypoxia signaling
      for the development of cardiovascular disease will be discussed.

PMID- 28757542
TI  - Isogroup Selection to Optimize Biocontrol Increases Cannibalism in Omnivorous
      (Zoophytophagous) Bugs.
AB  - Zoophytophagous insects can substitute animals for plant resources when prey is
      scarce. Many arthropods feed on conspecifics to survive in these conditions. An
      individual's tendency for cannibalism may depend on its genotype along with its
      diet specialization, in interaction with the availability of alternative food
      resources. We compared two isogroup lines of the zoophytophagous mullein bug,
      either specialized on animal or on plant diets, that were generated to improve
      biocontrol. We predicted that: (1) bugs from the prey-specialized line would show
      higher levels of cannibalism than bugs from the pollen-specialized line, and (2)
      both lines would decrease cannibalism levels in the presence of their preferred
      resource. Under laboratory conditions, large nymphal instars had 24 hours to feed
      on smaller instars, in the absence of additional resources, or with either spider
      mites or pollen present. Cannibalism was reduced by the availability of both prey
      and pollen, although prey had a lower effect than pollen. The intensity of
      cannibalism was always higher in the prey-specialized line than in the pollen
      specialized line, regardless of the availability of supplemented resources. The
      pollen-specialized line had decreased cannibalism levels only when pollen was
      available. These results indicate that cannibalism is a potentially regulating
      force in the prey-specialized line, but not in the pollen-specialized line.

PMID- 28757543
TI  - Responses of Crop Pests and Natural Enemies to Wildflower Borders Depends on
      Functional Group.
AB  - Increased homogeneity of agricultural landscapes in the last century has led to a
      loss of biodiversity and ecosystem services. However, management practices such
      as wildflower borders offer supplementary resources to many beneficial
      arthropods. There is evidence that these borders can increase beneficial
      arthropod abundance, including natural enemies of many pests. However, this
      increase in local habitat diversity can also have effects on pest populations,
      and these effects are not well-studied. In this study, we investigated how
      wildflower borders affect both natural enemies and pests within an adjacent
      strawberry crop. Significantly more predators were captured in strawberry
      plantings with wildflower borders versus plantings without wildflowers, but this
      effect depended on sampling method. Overall, herbivore populations were lower in
      plots with a wildflower border; however, responses to wildflower borders varied
      across specific pest groups. Densities of Lygus lineolaris (Tarnished Plant Bug),
      a generalist pest, increased significantly in plots that had a border, while
      Stelidota geminata (Strawberry Sap Beetle) decreased in strawberry fields with a
      wildflower border. These results suggest that wildflower borders may support the
      control of some pest insects; however, if the pest is a generalist and can
      utilize the resources of the wildflower patch, their populations may increase
      within the crop.

PMID- 28757544
TI  - A Novel Dual Separate Paths (DSP) Algorithm Providing Fault-Tolerant
      Communication for Wireless Sensor Networks.
AB  - Fault tolerance has long been a major concern for sensor communications in fault
      tolerant cyber physical systems (CPSs). Network failure problems often occur in
      wireless sensor networks (WSNs) due to various factors such as the insufficient
      power of sensor nodes, the dislocation of sensor nodes, the unstable state of
      wireless links, and unpredictable environmental interference. Fault tolerance is
      thus one of the key requirements for data communications in WSN applications.
      This paper proposes a novel path redundancy-based algorithm, called dual separate
      paths (DSP), that provides fault-tolerant communication with the improvement of
      the network traffic performance for WSN applications, such as fault-tolerant
      CPSs. The proposed DSP algorithm establishes two separate paths between a source
      and a destination in a network based on the network topology information. These
      paths are node-disjoint paths and have optimal path distances. Unicast frames are
      delivered from the source to the destination in the network through the dual
      paths, providing fault-tolerant communication and reducing redundant unicast
      traffic for the network. The DSP algorithm can be applied to wired and wireless
      networks, such as WSNs, to provide seamless fault-tolerant communication for
      mission-critical and life-critical applications such as fault-tolerant CPSs. The
      analyzed and simulated results show that the DSP-based approach not only provides
      fault-tolerant communication, but also improves network traffic performance. For
      the case study in this paper, when the DSP algorithm was applied to high
      availability seamless redundancy (HSR) networks, the proposed DSP-based approach
      reduced the network traffic by 80% to 88% compared with the standard HSR
      protocol, thus improving network traffic performance.

PMID- 28757545
TI  - The AGPase Family Proteins in Banana: Genome-Wide Identification, Phylogeny, and
      Expression Analyses Reveal Their Involvement in the Development, Ripening, and
      Abiotic/Biotic Stress Responses.
AB  - ADP-glucose pyrophosphorylase (AGPase) is the first rate-limiting enzyme in
      starch biosynthesis and plays crucial roles in multiple biological processes.
      Despite its importance, AGPase is poorly studied in starchy fruit crop banana
      (Musa acuminata L.). In this study, eight MaAGPase genes have been identified
      genome-wide in M. acuminata, which could be clustered into the large (APL) and
      small (APS) subunits. Comprehensive transcriptomic analysis revealed temporal and
      spatial expression variations of MaAPLs and MaAPSs and their differential
      responses to abiotic/biotic stresses in two banana genotypes, Fen Jiao (FJ) and
      BaXi Jiao (BX). MaAPS1 showed generally high expression at various developmental
      and ripening stages and in response to abiotic/biotic stresses in both genotypes.
      MaAPL-3 and -2a were specifically induced by abiotic stresses including cold,
      salt, and drought, as well as by fungal infection in FJ, but not in BX. The
      presence of hormone-related and stress-relevant cis-acting elements in the
      promoters of MaAGPase genes suggests that MaAGPases may play an important role in
      multiple biological processes. Taken together, this study provides new insights
      into the complex transcriptional regulation of AGPases, underlying their key
      roles in promoting starch biosynthesis and enhancing stress tolerance in banana.

PMID- 28757547
TI  - High-Temporal-Resolution High-Spatial-Resolution Spaceborne SAR Based on
      Continuously Varying PRF.
AB  - Synthetic Aperture Radar (SAR) is a well-established and powerful imaging
      technique for acquiring high-spatial-resolution images of the Earth's surface.
      With the development of beam steering techniques, sliding spotlight and staring
      spotlight modes have been employed to support high-spatial-resolution
      applications. In addition to this strengthened high-spatial-resolution and wide
      swath capability, high-temporal-resolution (short repeat-observation interval)
      represents a key capability for numerous applications. However, conventional SAR
      systems are limited in that the same patch can only be illuminated for several
      seconds within a single pass. This paper considers a novel high-squint-angle
      system intended to acquire high-spatial-resolution spaceborne SAR images with
      repeat-observation intervals varying from tens of seconds to several minutes
      within a single pass. However, an exponentially increased range cell migration
      would arise and lead to a conflict between the receive window and 'blind ranges'.
      An efficient data acquisition technique for high-temporal-resolution, high
      spatial-resolution and high-squint-angle spaceborne SAR, in which the pulse
      repetition frequency (PRF) is continuously varied according to the changing slant
      range, is presented in this paper. This technique allows echo data to remain in
      the receive window instead of conflicting with the transmitted pulse or nadir
      echo. Considering the precision of hardware, a compromise and practical strategy
      is also proposed. Furthermore, a detailed performance analysis of range
      ambiguities is provided with respect to parameters of TerraSAR-X. For strong
      point-like targets, the range ambiguity of this technique would be better than
      that of uniform PRF technique. For this innovative technique, a resampling
      strategy and modified imaging algorithm have been developed to handle the non
      uniformly sampled echo data. Simulations are performed to validate the efficiency
      of the proposed technique and the associated imaging algorithm.

PMID- 28757546
TI  - Roles of Wnt Target Genes in the Journey of Cancer Stem Cells.
AB  - The importance of Wnt/beta-catenin signaling in cancer stem cells (CSCs) has been
      acknowledged; however, the mechanism through which it regulates the biological
      function of CSCs and promotes cancer progression remains elusive. Hence, to
      understand the intricate mechanism by which Wnt controls stemness, the specific
      downstream target genes of Wnt were established by analyzing the genetic
      signatures of multiple types of metastatic cancers based on gene set enrichment.
      By focusing on the molecular function of Wnt target genes, the biological roles
      of Wnt were interpreted in terms of CSC dynamics from initiation to metastasis.
      Wnt signaling participates in cancer initiation by generating CSCs from normal
      stem cells or non-CSCs and augmenting persistent growth at the primary region,
      which is resistant to anti-cancer therapy. Moreover, it assists CSCs in invading
      nearby tissues and in entering the blood stream, during which the negative
      feedback of the Wnt signaling pathway maintains CSCs in a dormant state that is
      suitable for survival. When CSCs arrive at distant organs, another burst of Wnt
      signaling induces CSCs to succeed in re-initiation and colonization. This
      comprehensive understanding of Wnt target genes provides a plausible explanation
      for how Wnt allows CSCs variation during cancer progression.

PMID- 28757550
TI  - Assessing Risks from Cyclones for Human Lives and Livelihoods in the Coastal
      Region of Bangladesh.
AB  - As a disaster prone country, Bangladesh is regularly hit by natural hazards,
      including devastating cyclones, such as in 1970, 1991 and 2007. Although the
      number of cyclones' fatalities reduced from 0.3 million in 1970 to a few thousand
      or fewer in recent events, loss of lives and impact on livelihoods remains a
      concern. It depends on the meteorological characteristics of cyclone and the
      general vulnerability and capacity of the exposed population. In that
      perspective, a spatially explicit risk assessment is an essential step towards
      targeted disaster risk reduction. This study aims at analyzing the spatial
      variation of the different factors contributing to the risk for coastal
      communities at regional scale, including the distribution of the hazards,
      exposure, vulnerability and capacity. An exploratory factor analysis method is
      used to map vulnerability contrasts between local administrative units. Indexing
      and ranking using geospatial techniques are used to produce maps of exposure,
      hazard, vulnerability, capacities and risk. Results show that vulnerable
      populations and exposed areas are distributed along the land sea boundary,
      islands and major inland rivers. The hazard, assessed from the density of
      historical cyclone paths, is highest in the southwestern part of the coast.
      Whereas cyclones shelters are shown to properly serve the most vulnerable
      populations as priority evacuation centers, the overall pattern of capacity
      accounting for building quality and road network shows a more complex pattern.
      Resultant risk maps also provide a reasonable basis from which to take further
      structural measures to minimize loss of lives in the upcoming cyclones.

PMID- 28757548
TI  - The Role of Epigenetic Regulation in Epstein-Barr Virus-Associated Gastric
      Cancer.
AB  - The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases
      throughout the world. In EBV-associated gastric carcinoma (EBVaGC), all tumor
      cells harbor the clonal EBV genome. The expression of latent EBV genes is
      strictly regulated through the methylation of EBV DNA. The methylation of viral
      DNA regulates the type of EBV latency, and methylation of the tumor suppressor
      genes is a key abnormality in EBVaGC. The methylation frequencies of several
      tumor suppressor genes and cell adhesion molecules are significantly higher in
      EBVaGC than in control cases. EBV-derived microRNAs repress translation from
      viral and host mRNAs. EBV regulates the expression of non-coding RNA in gastric
      carcinoma. With regard to the clinical application of demethylating agents
      against EBVaGC, we investigated the effects of decitabine against the EBVaGC cell
      lines. Decitabine inhibited the cell growth of EBVaGC cells. The promoter regions
      of p73 and Runt-related transcription factor 3(RUNX3) were demethylated, and
      their expression was upregulated by the treatment. We review the role of
      epigenetic regulation in the development and maintenance of EBVaGC and discuss
      the therapeutic application of DNA demethylating agents for EBVaGC.

PMID- 28757551
TI  - Evaluating the Effectiveness of Implementing a More Severe Drunk-Driving Law in
      China: Findings from Two Open Access Data Sources.
AB  - In 2011, China implemented a more severe drunk-driving law. This study evaluated
      the effectiveness of the law on road traffic morbidity and mortality attributed
      to alcohol use. Data were from two open-access data sources, the Global Burden of
      Disease (GBD) 2015 update and police data. Poisson regression examined the
      significance of changes in morbidity and mortality. Large gaps in crude death
      estimates from road traffic crashes attributed to alcohol use emerged between the
      two data sources. For the GBD 2015 update, crude and age-standardized mortality
      displayed consistent trends between 1990 and 2015; age-standardized mortality per
      100,000 persons increased from 5.71 in 1990 to 7.48 in 2005 and then continuously
      decreased down to 5.94 in 2015. Police data showed a decrease for crude mortality
      per 100,000 persons from 0.29 in 2006 to 0.15 in 2010 and then an increase to
      0.19 in 2015. We conclude available data are inadequate to determine the
      effectiveness of the implementation of the more severe drunk-driving law in China
      since the two data sources present highly inconsistent results. Further effort is
      needed to tackle data inconsistencies and obtain reliable and accurate data on
      road traffic injury attributable to alcohol use in China.

PMID- 28757549
TI  - Updated Insight into the Physiological and Pathological Roles of the Retromer
      Complex.
AB  - Retromer complexes mediate protein trafficking from the endosomes to the trans
      Golgi network (TGN) or through direct recycling to the plasma membrane. In yeast,
      they consist of a conserved trimer of the cargo selective complex (CSC), Vps26
      Vps35-Vps29 and a dimer of sorting nexins (SNXs), Vps5-Vps17. In mammals, the CSC
      interacts with different kinds of SNX proteins in addition to the mammalian
      homologues of Vps5 and Vps17, which further diversifies retromer functions. The
      retromer complex plays important roles in many cellular processes including
      restriction of invading pathogens. In this review, we summarize some recent
      developments in our understanding of the physiological and pathological functions
      of the retromer complex.

PMID- 28757552
TI  - Effects of P-Glycoprotein on the Transport of DL0410, a Potential Multifunctional
      Anti-Alzheimer Agent.
AB  - In our study, we attempted to investigate the influences of P-glycoprotein (P-gp)
      on DL0410, a novel synthetic molecule for Alzheimer's disease (AD) treatment, for
      intestinal absorption and blood-brain barrier permeability in vitro and related
      binding mechanisms in silico. Caco-2, MDCK, and MDCK-MDR1 cells were utilized for
      transport studies, and homology modelling of human P-gp was built for further
      docking study to uncover the binding mode of DL0410. The results showed that the
      apparent permeability (Papp) value of DL0410 was approximately 1 * 10-6 cm/s,
      indicating the low permeability of DL0410. With the presence of verapamil, the
      directional transport of DL0410 disappeared in Caco-2 and MDCK-MDR1 cells,
      suggesting that DL0410 should be a substrate of P-gp, which was also confirmed by
      P-gp ATPase assay. In addition, DL0410 could competitively inhibit the transport
      of Rho123, a P-gp known substrate. According to molecular docking, we also found
      that DL0410 could bind to the drug binding pocket (DBP), but not the nucleotide
      binding domain (NBD). In conclusion, DL0410 was a substrate as well as a
      competitive inhibitor of P-gp, and P-gp had a remarkable impact on the intestine
      and brain permeability of DL0410, which is of significance for drug research and
      development.

PMID- 28757553
TI  - Miniaturisation of Pressure-Sensitive Paint Measurement Systems Using Low-Cost,
      Miniaturised Machine Vision Cameras.
AB  - Measurements of pressure-sensitive paint (PSP) have been performed using new or
      non-scientific imaging technology based on machine vision tools. Machine vision
      camera systems are typically used for automated inspection or process monitoring.
      Such devices offer the benefits of lower cost and reduced size compared with
      typically scientific-grade cameras; however, their optical qualities and
      suitability have yet to be determined. This research intends to show relevant
      imaging characteristics and also show the applicability of such imaging
      technology for PSP. Details of camera performance are benchmarked and compared to
      standard scientific imaging equipment and subsequent PSP tests are conducted
      using a static calibration chamber. The findings demonstrate that machine vision
      technology can be used for PSP measurements, opening up the possibility of
      performing measurements on-board small-scale model such as those used for wind
      tunnel testing or measurements in confined spaces with limited optical access.

PMID- 28757554
TI  - Multifunctional Cinnamic Acid Derivatives.
AB  - Our research to discover potential new multitarget agents led to the synthesis of
      10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol,
      naphth-1-ol, and (benzylamino) ethan-1-ol. The synthesized molecules were
      evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for
      their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and
      propranolol showed the highest lipoxygenase (LOX) inhibition (IC50 = 6 MUMU) and
      antiproteolytic activity (IC50 = 0.425 MUMU). The conjugate 1a of simple cinnamic
      acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315
      MUMU) and good LOX inhibitory activity (IC50 = 66 MUMU). Compounds 3a and 3b,
      derived from methoxylated caffeic acid present a promising combination of in
      vitro inhibitory and antioxidative activities. The S isomer of 2b also presented
      an interesting multitarget biological profile in vitro. Molecular docking studies
      point to the fact that the theoretical results for LOX-inhibitor binding are
      identical to those from preliminary in vitro study.

PMID- 28757555
TI  - Detection of Pseudomonas aeruginosa Metabolite Pyocyanin in Water and Saliva by
      Employing the SERS Technique.
AB  - Pyocyanin (PYO) is a metabolite specific for Pseudomonas aeruginosa. In the case
      of immunocompromised patients, it is currently considered a biomarker for life
      threating Pseudomonas infections. In the frame of this study it is shown, that
      PYO can be detected in aqueous solution by employing surface-enhanced Raman
      spectroscopy (SERS) combined with a microfluidic platform. The achieved limit of
      detection is 0.5 MUM. This is ~2 orders of magnitude below the concentration of
      PYO found in clinical samples. Furthermore, as proof of principle, the SERS
      detection of PYO in the saliva of three volunteers was also investigated. This
      body fluid can be collected in a non-invasive manner and is highly chemically
      complex, making the detection of the target molecule challenging. Nevertheless,
      PYO was successfully detected in two saliva samples down to 10 MUM and in one
      sample at a concentration of 25 MUM. This indicates that the molecules present in
      saliva do not inhibit the efficient adsorption of PYO on the surface of the
      employed SERS active substrates.

PMID- 28757557
TI  - Applications Based on Service-Oriented Architecture (SOA) in the Field of Home
      Healthcare.
AB  - This article makes a literature review of applications developed in the health
      industry which are focused on patient care from home and implement a service
      oriented (SOA) design in architecture. Throughout this work, the applicability of
      the concept of Internet of Things (IoT) in the field of telemedicine and health
      care in general is evaluated. It also performs an introduction to the concept of
      SOA and its main features, making a small emphasis on safety aspects. As a
      central theme, the description of different solutions that can be found in the
      health industry is developed, especially those whose goal is health care at home;
      the main component of these solutions are body sensor networks. Finally, an
      analysis of the literature from the perspectives of functionalities, security
      implementation and semantic interoperability is made to have a better
      understanding of what has been done and which are probable research paths to be
      studied in the future.

PMID- 28757556
TI  - Expression of Serum Exosomal and Esophageal MicroRNA in Rat Reflux Esophagitis.
AB  - Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal
      disease. However, the role of exosomal microRNAs (miRNAs) and esophageal miRNAs
      in GERD has not been studied. A rat model of acid reflux esophagitis was used to
      establish a novel diagnosis marker for GERD and examine dynamics of miRNA
      expression in GERD. Rats were sacrificed 3 (acute phase), 7 (sub-acute phase) and
      21 days (chronic phase) after induction of esophagitis. Exosomes were extracted
      from serum, and the expression patterns of serum miRNAs were analyzed. Four
      upregulated miRNAs (miR-29a-3p, 128-3p, 223-3p and 3473) were identified by
      microarray analysis. The expression levels of exosomal miR-29a-3p were
      significantly higher in the chronic phase of reflux esophagitis compared with
      controls, and increased expression of miR-29a-3p was specific to chronic reflux
      esophagitis. Esophageal miR-223-3p expression was higher compared with controls,
      and gradually decreased from acute to chronic phase in esophagitis. In
      conclusion, exosomal miR-29a-3p and esophageal miR-223-3p might play roles in
      GERD.

PMID- 28757558
TI  - The Bionomics of the Cocoa Mealybug, Exallomochlus hispidus (Morrison)
      (Hemiptera: Pseudococcidae), on Mangosteen Fruit and Three Alternative Hosts.
AB  - The cocoa mealybug, Exallomochlus hispidus Morrison (Hemiptera: Pseudococcidae)
      is known to attack mangosteen, an important fruit export commodity for Indonesia.
      The mealybug is polyphagous, so alternative host plants can serve as a source of
      nourishment. This study aimed to record the bionomics of E. hispidus on
      mangosteen (Garcinia mangostana L.) and three alternative hosts, kabocha squash
      (Cucurbita maxima L.), soursop (Annona muricata, L.), and guava (Psidium guajava
      L.). First-instar nymphs of the E. hispidus were reared at room temperature on
      mangosteen, kabocha, soursop, and guava fruits until they developed into adults
      and produced nymphs. Female E. hispidus go through three instar stages before
      adulthood. The species reproduces by deuterotokous parthenogenesis. Exallomochlus
      hispidus successfully developed and reproduced on all four hosts. The shortest
      life cycle of the mealybug occurred on kabocha (about 32.4 days) and the longest
      was on guava (about 38.3 days). The highest fecundity was found on kabocha (about
      100 nymphs/female) and the lowest on mangosteen (about 46 nymphs/female). The
      shortest oviposition period was 10 days on mangosteen and the longest, 10 days,
      on guava. These findings could be helpful in controlling E. hispidus populations
      in orchards.

PMID- 28757559
TI  - In-Network Computation of the Optimal Weighting Matrix for Distributed Consensus
      on Wireless Sensor Networks.
AB  - In a network, a distributed consensus algorithm is fully characterized by its
      weighting matrix. Although there exist numerical methods for obtaining the
      optimal weighting matrix, we have not found an in-network implementation of any
      of these methods that works for all network topologies. In this paper, we propose
      an in-network algorithm for finding such an optimal weighting matrix.

PMID- 28757560
TI  - Microorganisms in Fermented Apple Beverages: Current Knowledge and Future
      Directions.
AB  - Production of fermented apple beverages is spread all around the world with
      specificities in each country. 'French ciders' refer to fermented apple juice
      mainly produced in the northwest of France and often associated with short
      periods of consumption. Research articles on this kind of product are scarce
      compared to wine, especially on phenomena associated with microbial activities.
      The wine fermentation microbiome and its dynamics, organoleptic improvement for
      healthy and pleasant products and development of starters are now widely studied.
      Even if both beverages seem close in terms of microbiome and process (with both
      alcoholic and malolactic fermentations), the inherent properties of the raw
      materials and different production and environmental parameters make research on
      the specificities of apple fermentation beverages worthwhile. This review
      summarizes current knowledge on the cider microbial ecosystem, associated
      activities and the influence of process parameters. In addition, available data
      on cider quality and safety is reviewed. Finally, we focus on the future role of
      lactic acid bacteria and yeasts in the development of even better or new
      beverages made from apples.

PMID- 28757561
TI  - Porcine Interferon Stimulated Gene 12a Restricts Porcine Reproductive and
      Respiratory Syndrome Virus Replication in MARC-145 Cells.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe losses
      in the global pig industry. In the present study, we investigated the molecular
      characterization of porcine interferon stimulated gene 12a (ISG12A) and confirmed
      its anti-PRRSV ability for the first time. We found that porcine ISG12A was
      localized in mitochondria and significantly decreased the number of cells in G2/S
      phase. Porcine ISG12A mRNA was up-regulated in cells/tissues of Tongcheng (TC)
      pigs and Large White (LW) pigs after PRRSV challenge. More importantly, the
      ectopic overexpression of ISG12A could significantly suppress PRRSV replication
      at 24, 36 and 48 h post challenge (hpc), which was confirmed by detecting PRRSV
      ORF7 mRNA with quantitative reverse transcription polymerase chain reaction (qRT
      PCR) and PRRSV N protein with indirect immunofluorescence assay (IFA) in MARC-145
      cells. Meanwhile, knockdown of endogenic ISG12A could obviously facilitate PRRSV
      replication in MARC-145 cells at 36 hpc. The results will lead to a better
      understanding of the interaction between host immune system and PRRSV, which may
      help us develop novel therapeutic tools to control PRRSV.

PMID- 28757563
TI  - Effect on Quality Characteristics of Tomatoes Grown Under Well-Watered and
      Drought Stress Conditions.
AB  - Tomatoes are one of the most nutritionally and economically important crops in
      New Zealand and around the world. Tomatoes require large amounts of water to grow
      well and are adversely affected by drought stress. However, few studies have
      evaluated the physicochemical characteristics of commercial tomatoes grown under
      water stress conditions. Four tomato cultivars (Incas, Marmande, Scoresby Dwarf,
      and Window Box Red) were grown in a greenhouse under well-watered and drought
      stress conditions and the tomatoes were harvested when ripe. The physicochemical
      properties and antioxidant contents of the fruits were compared. There were
      significant differences between cultivars in quality characteristics-such as dry
      matter, total soluble solids, and pH parameters-but there were no differences in
      the quality characteristics between the two treatments of the fruits (p > 0.05);
      however, there were significant differences (p < 0.05) in the antioxidant
      compositions (lycopene, total phenolics, and flavonoids) and antioxidant
      activities (DPPH and ABTS) of the fruits of both cultivars and treatments.
      Overall, these results indicated that tomatoes increased their bioactive
      compounds without changing any quality characteristics when exposed to water
      stress conditions.

PMID- 28757562
TI  - Unusual Antioxidant Properties of 26S Proteasome Isolated from Cold-Adapted
      Organisms.
AB  - The oxidative challenge represents an important factor affecting the adaptive
      strategies in Antarctic fish, but their impact on the protein degradation
      machinery still remains unclear. The previous analysis of the first 26S
      proteasome from the Antarctic red-blooded fish Trematomus bernacchii, evidenced
      improved antioxidant functions necessary to counteract the environmental pro
      oxidant conditions. The purpose of this work was to carry out a study on 26S
      proteasomes from the temperate red-blooded Dicenthrarcus labrax and the icefish
      Chionodraco hamatus in comparison with the isoform already described from T.
      bernacchii, to better elucidate the cold-adapted physiological functions of this
      complex. Therefore, the 26S isoforms were isolated and the complementary DNAs
      (cDNAs) codifying the catalytic subunits were cloned. The biochemical
      characterization of Antarctic 26S proteasomes revealed their significantly higher
      structural stability and resistance to H2O2 with respect to that of the temperate
      counterpart, as also suggested by a comparative modeling analysis of the
      catalytic subunits. Moreover, in contrast to that observed in T. bernacchii, the
      26S systems from C. hamatus and D. labrax were incapable to hydrolyze oxidized
      proteins in a ubiquitin-independent manner. Therefore, the 'uncommon' properties
      displayed by the Antarctic 26S proteasomes can mirror the impact exercised by
      evolutionary pressure in response to richly oxygenated environments.

PMID- 28757564
TI  - A Brief Review of OPT101 Sensor Application in Near-Infrared Spectroscopy
      Instrumentation for Intensive Care Unit Clinics.
AB  - The optoelectronic sensor OPT101 have merits in advanced optoelectronic response
      characteristics at wavelength range for medical near-infrared spectroscopy and
      small-size chip design with build-in trans-impedance amplifier. Our lab is
      devoted to developing a series of portable near-infrared spectroscopy (NIRS)
      devices embedded with OPT101 for applications in intensive care unit clinics,
      based on NIRS principle. Here we review the characteristics and advantages of
      OPT101 relative to clinical NIRS instrumentation, and the most recent
      achievements, including early-diagnosis and therapeutic effect evaluation of
      thrombus, noninvasive monitoring of patients' shock severity, and fatigue
      evaluation. The future prospect on OPT101 improvements in noninvasive clinical
      applications is also discussed.

PMID- 28757565
TI  - The Pharmaceutical Device Prisma(r) Skin Promotes in Vitro Angiogenesis through
      Endothelial to Mesenchymal Transition during Skin Wound Healing.
AB  - Glycosaminoglycans are polysaccharides of the extracellular matrix supporting
      skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as
      chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of
      Prisma(r) Skin, a pharmaceutical device developed by Mediolanum Farmaceutici
      S.p.a. Here, we show the in vitro effects of this device in the new vessels
      formation by endothelial cells, since angiogenesis represents a key moment in
      wound healing. We found a strong increase of migration and invasion rates of
      these cells treated with mesoglycan and Prisma(r) Skin which mediate the
      activation of the pathway triggered by CD44 receptor. Furthermore, endothelial
      cells form longer capillary-like structures with a great number of branches, in
      the presence of the same treatments. Thus, the device, thanks to the mesoglycan,
      leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the
      switch to a fibroblast-like phenotype, as shown by immunofluorescence assays.
      Finally, we found that mesoglycan and Prisma(r) Skin inhibit inflammatory
      reactions such as nitric oxide secretion and NF-kappaB nuclear translocation in
      endothelial cells and Tumor Necrosis Factor-alpha production by macrophages. In
      conclusion, based on our data, we suggest that Prisma(r) Skin may be able to
      accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding
      chronic, thus pathological, responses.

PMID- 28757566
TI  - Health Inequities among Lesbian, Gay, and Bisexual Adults in North Carolina, 2011
      2014.
AB  - Inequalities in health have been identified for lesbian, gay, and bisexual (LGB)
      populations nationally. Policies in the U.S. South offer fewer protections for
      LGB people than in other regions, yet, limited data exist for this region. North
      Carolina (NC) BRFSS data from 2011 to 2014 were combined (LGB n = 604;
      heterosexual n = 33,170) and analyzed using SAS survey procedures to estimate
      health characteristics by sexual orientation within gender. Many examined
      indicators were not different by sexual orientation, however, other results were
      significant and consistent with findings from state population surveys in other
      regions of the country. Both genders showed inequities in mental health, having
      over twice the odds of five or more poor mental health days in the past month and
      of having ever been diagnosed with a depressive disorder. Sexual minority women
      had higher odds compared with heterosexual women for ever having smoked
      cigarettes, current smoking, exposure to secondhand smoke both in the workplace
      and at home, and both alcohol risk factors, binge and heavy drinking. Being part
      of the LGB population in NC is associated with worse health. The implementation
      of anti-LGB policies in the NC warrants ongoing monitoring of LGB health
      inequities in NC and in other southeastern states for potential effects on the
      health and well-being of sexual minorities.

PMID- 28757567
TI  - Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension.
AB  - Pulmonary hypertension (PH) is a heterogeneous disorder associated with a poor
      prognosis. Thus, the development of novel treatment strategies is of great
      interest. The enzyme arginase (Arg) is emerging as important player in PH
      development. The aim of the current study was to determine the expression of ArgI
      and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was
      induced in 35 Sprague-Dawley rats by monocrotaline (MCT, 60 mg/kg as single
      dose). There were three experimental groups: sham-treated controls (control
      group, n = 11), MCT-induced PH (MCT group, n = 11) and MCT-induced PH treated
      with the Arg inhibitor Nomega-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha
      group, n = 13). ArgI and ArgII expression was determined by immunohistochemistry
      and Western blot. Right ventricular systolic pressure (RVPsys) was measured and
      lung tissue remodeling was determined. Induction of PH resulted in an increase in
      RVPsys (81 +/- 16 mmHg) compared to the control group (41 +/- 15 mmHg, p = 0.002)
      accompanied by a significant elevation of histological sum-score (8.2 +/- 2.4 in
      the MCT compared to 1.6 +/- 1.6 in the control group, p < 0.001). Both, ArgI and
      ArgII were relevantly expressed in lung tissue and there was a significant
      increase in the MCT compared to the control group (p < 0.01). Arg inhibition
      resulted in a significant reduction of RVPsys to 52 +/- 19 mmHg (p = 0.006) and
      histological sum-score to 5.8 +/- 1.4 compared to the MCT group (p = 0.022). PH
      leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys
      and diminished lung tissue remodeling and therefore represents a potential
      treatment strategy in PH.

PMID- 28757568
TI  - Electronic Spectroscopy of Phthalocyanine and Porphyrin Derivatives in Superfluid
      Helium Nanodroplets.
AB  - Phthalocyanine and porphyrin were among the first organic compounds investigated
      by means of electronic spectroscopy in superfluid helium nanodroplets. Superfluid
      helium nanodroplets serve as a very gentle host system for preparing cold and
      isolated molecules. The uniqueness of helium nanodroplets is with respect to the
      superfluid phase which warrants the vanishing viscosity and, thus, minimal
      perturbation of the dopant species at a temperature as low as 0.37 K. These are
      ideal conditions for the study of molecular spectra in order to analyze
      structures as well as dynamic processes. Besides the investigation of the dopant
      species itself, molecular spectroscopy in helium droplets provides information on
      the helium droplet and in particular on microsolvation. This article, as part of
      a special issue on phthalocyanines and porphyrins, reviews electronic
      spectroscopy of phthalocyanine and porphyrin compounds in superfluid helium
      nanodroplets. In addition to the wide variety of medical as well as technical and
      synthetical aspects, this article discusses electronic spectroscopy of
      phthalocyanines and porphyrins in helium droplets in order to learn about both
      the dopant and the helium environment.

PMID- 28757569
TI  - Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting
      the Mycobacterium tuberculosis HU Protein.
AB  - Tuberculosis continues to be a great source of concern in global health because
      of the large reservoir of humans infected with the bacilli and the appearance of
      clinical isolates resistant to a wide array of anti-tuberculosis drugs. New drugs
      with novel mechanisms of action on new targets are urgently required to reduce
      global tuberculosis burden. Mycobacterium tuberculosis nucleoid associated
      protein (NAP) HU has been shown to be druggable and essential for the organism's
      survival. In this study, four diarylethenes were synthesized using a one-pot
      decarboxylated Heck-coupling of coumaric acids with iodoanisoles. The prepared
      compounds 1-4 were tested for their in vitro growth inhibition of M. tuberculosis
      H37Rv using the spot culture growth inhibition assay, displaying minimum
      inhibitory concentrations between 9 and 22 uM. Their cytotoxicity against BHK-21
      cell line showed half inhibition at concentrations between 98 and 729 uM. The
      most selective hit (SI = 81), demonstrated inhibition of M. tuberculosis HU
      protein involved in maintaining bacterial genome architecture.

PMID- 28757570
TI  - Monitoring of Pesticide Residues in Commonly Used Fruits and Vegetables in
      Kuwait.
AB  - The presence of pesticide residues in primary and derived agricultural products
      raises serious health concerns for consumers. The aim of this study was to assess
      the level of pesticide residues in commonly consumed fruits and vegetables in
      Kuwait. A total of 150 samples of different fresh vegetables and fruits were
      analyzed for the presence of 34 pesticides using the quick easy cheap effective
      rugged and safe (QuEChERS) multi-residue extraction, followed by gas
      chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). Pesticide residues above the maximum residue limits
      (MRL) were detected in 21% of the samples and 79% of the samples had no residues
      of the pesticides surveyed or contained residues below the MRL. Multiple residues
      were present in 40% of the samples with two to four pesticides, and four samples
      were contaminated with more than four pesticide residues. Of the pesticides
      investigated, 16 were detected, of which imidacloprid, deltamethrin,
      cypermethrin, malathion, acetamiprid, monocrotophos, chlorpyrifos-methyl, and
      diazinon exceeded their MRLs. Aldrin, an organochlorine pesticide, was detected
      in one apple sample, with residues below the MRL. The results indicate the
      occurrence of pesticide residues in commonly consumed fruits and vegetables in
      Kuwait, and pointed to an urgent need to develop comprehensive intervention
      measures to reduce the potential health risk to consumers. The need for the
      regular monitoring of pesticide residues and the sensitization of farmers to
      better pesticide safety practices, especially the need to adhere to recommended
      pre-harvest intervals is recommended.

PMID- 28757571
TI  - Preliminary Assessment of Wind and Wave Retrieval from Chinese Gaofen-3 SAR
      Imagery.
AB  - The Chinese Gaofen-3 (GF-3) synthetic aperture radar (SAR) launched by the China
      Academy of Space Technology (CAST) has operated at C-band since September 2016.
      To date, we have collected 16/42 images in vertical-vertical (VV)/horizontal
      horizontal (HH) polarization, covering the National Data Buoy Center (NDBC) buoy
      measurements of the National Oceanic and Atmospheric Administration (NOAA) around
      U.S. western coastal waters. Wind speeds from NDBC in situ buoys are up to 15 m/s
      and buoy-measured significant wave height (SWH) has ranged from 0.5 m to 3 m. In
      this study, winds were retrieved using the geophysical model function (GMF)
      together with the polarization ratio (PR) model and waves were retrieved using a
      new empirical algorithm based on SAR cutoff wavelength in satellite flight
      direction, herein called CSAR_WAVE. Validation against buoy measurements shows a
      1.4/1.9 m/s root mean square error (RMSE) of wind speed and a 24/23% scatter
      index (SI) of SWH for VV/HH polarization. In addition, wind and wave retrieval
      results from 166 GF-3 images were compared with the European Centre for Medium
      Range Weather Forecasts (ECMWF) re-analysis winds, as well as the SWH from the
      WaveWatch-III model, respectively. Comparisons show a 2.0 m/s RMSE for wind speed
      with a 36% SI of SWH for VV-polarization and a 2.2 m/s RMSE for wind speed with a
      37% SI of SWH for HH-polarization. Our work gives a preliminary assessment of the
      wind and wave retrieval results from GF-3 SAR images for the first time and will
      provide guidance for marine applications of GF-3 SAR.

PMID- 28757573
TI  - Unambiguous Imaging of Static Scenes and Moving Targets with the First Chinese
      Dual-Channel Spaceborne SAR Sensor.
AB  - Multichannel synthetic aperture radar (SAR) is a breakthrough given the inherent
      limitation between high-resolution and wide-swath (HRWS) faced with conventional
      SAR. This paper aims to obtain unambiguous imaging of static scenes and moving
      targets with the first Chinese dual-channel spaceborne SAR sensor. We propose an
      integrated imaging scheme with the dual-channel echoes. In the imaging scheme,
      the subspace-based error estimation algorithm is first applied to the spaceborne
      multichannel SAR system, followed by the reconstruction algorithm prior to
      imaging. The motion-adapted reconstruction algorithm for moving target imaging is
      initially achieved with the spaceborne multichannel SAR system. The results
      exhibit an effective suppression of azimuth ambiguities and false targets with
      the proposed process. This paper verifies the accuracy of the subspace-based
      channel error estimator and the feasibility of the motion-adapted reconstruction
      algorithm. The proposed imaging process has prospects for future HRWS SAR systems
      with more channels.

PMID- 28757572
TI  - Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to
      Rationally Designed Meta-Biomaterials.
AB  - Recent advances in additive manufacturing (AM) techniques in terms of accuracy,
      reliability, the range of processable materials, and commercial availability have
      made them promising candidates for production of functional parts including those
      used in the biomedical industry. The complexity-for-free feature offered by AM
      means that very complex designs become feasible to manufacture, while batch-size
      indifference enables fabrication of fully patient-specific medical devices.
      Design for AM (DfAM) approaches aim to fully utilize those features for
      development of medical devices with substantially enhanced performance and
      biomaterials with unprecedented combinations of favorable properties that
      originate from complex geometrical designs at the micro-scale. This paper reviews
      the most important approaches in DfAM particularly those applicable to additive
      bio-manufacturing including image-based design pipelines, parametric and non
      parametric designs, metamaterials, rational and computationally enabled design,
      topology optimization, and bio-inspired design. Areas with limited research have
      been identified and suggestions have been made for future research. The paper
      concludes with a brief discussion on the practical aspects of DfAM and the
      potential of combining AM with subtractive and formative manufacturing processes
      in so-called hybrid manufacturing processes.

PMID- 28757574
TI  - Finding a Balance between Protection and Pathology: The Dual Role of Perforin in
      Human Disease.
AB  - Perforin is critical for controlling viral infection and tumor surveillance.
      Clinically, mutations in perforin are viewed as unfavorable, as lack of this pore
      forming protein results in lethal, childhood disease, familial hemophagocytic
      lymphohistiocytosis type 2 (FHL 2). However, many mutations in the coding region
      of PRF1 are not yet associated with disease. Animal models of viral-associated
      blood-brain barrier (BBB) disruption and experimental cerebral malaria (ECM) have
      identified perforin as critical for inducing pathologic central nervous system
      CNS vascular permeability. This review focuses on the role of perforin in both
      protecting and promoting human disease. It concludes with a novel hypothesis that
      diversity observed in the PRF1 gene may be an example of selective advantage that
      protects an individual from perforin-mediated pathology, such as BBB disruption.

PMID- 28757575
TI  - Vaccination with Recombinant Baculovirus Expressing Ranavirus Major Capsid
      Protein Induces Protective Immunity in Chinese Giant Salamander, Andrias
      davidianus.
AB  - The Chinese giant salamander iridovirus (CGSIV), belonging to the genus Ranavirus
      in the family Iridoviridae, is the causative agent of an emerging infectious
      disease causing high mortality of more than 90% and economic losses in Chinese
      giant salamanders in China. In this study, a recombinant baculovirus-based
      vaccine expressing the CGSIV major capsid protein (MCP) was developed and its
      protective immunity in Chinese giant salamanders was evaluated. The recombinant
      Autographacalifornica nucleopolyhedrosis virus (AcNPV), expressing CGSIV MCP,
      designated as AcNPV-MCP, was generated with the highest titers of 1 * 108 plaque
      forming units/mL (PFU/mL) and confirmed by Western blot and indirect
      immunofluorescence (IIF) assays. Western blot analysis revealed that the
      expressed MCP reacted with mouse anti-MCP monoclonal antibodies at the band of
      about 53 kDa. The results of IIF indicated that the MCP was expressed in the
      infected Spodoptera frugiperda 9 (Sf9) cells with the recombinant baculovirus,
      and the Chinese giant salamander muscle cells also transduced with the AcNPV-MCP.
      Immunization with the recombinant baculovirus of AcNPV-MCP elicited robust
      specific humoral immune responses detected by ELISA and neutralization assays and
      potent cellular immune responses in Chinese giant salamanders. Importantly, the
      effective immunization conferred highly protective immunity for Chinese giant
      salamanders against CGSIV challenge and produced a relative percent of survival
      rate of 84%. Thus, the recombinant baculovirus expressing CGSIV MCP can induce
      significant immune responses involving both humoral and cell-mediated immunity in
      Chinese giant salamanders and might represent a potential baculovirus based
      vaccine candidate for Chinese giant salamanders against CGSIV.

PMID- 28757576
TI  - The Association between Cardiorespiratory Fitness and Gut Microbiota Composition
      in Premenopausal Women.
AB  - The aim of this study was to investigate the association between
      cardiorespiratory fitness and gut microbiota composition in premenopausal women.
      The participants consisted of 71 premenopausal Finnish women (aged 19-49 years).
      Gut microbiota were analyzed using flow cytometry, 16S rRNA gene hybridization
      and DNA-staining. Maximum oxygen uptake (VO2max) was assessed by respiratory gas
      analyzer and body composition by Bioimpdance. We found that participants with low
      VO2max had lower Bacteroides, but higher Eubacterium rectale-Clostridium
      coccoides than the high VO2max group (p < 0.05 for all). VO2max was inversely
      associated with EreC (r = -0.309, p = 0.01) but not with other bacteria. VO2max
      also negatively correlated with fat% (r = -0.755, p < 0.001), triglycerides (r = 
      0.274, p = 0.021) and leptin (r = -0.574, p < 0.001). By contrast, EreC was
      positively associated with fat% (r = 0.382, p = 0.002), dietary fat intake (r =
      0.258, p = 0.034), triglycerides (r = 0.390, p = 0.002) and leptin (r = 0.424, p
      = 0.001), but negatively with carbohydrate intake (r = -0.252, p = 0.034) and HDL
      (r = -0.26, p = 0.028). After adjusting for age and dietary intake, all the
      significant associations remained. However, after adjusting for fat%, the
      associations between VO2max and EreC disappeared. Our results suggest that
      cardiorespiratory fitness is associated with gut microbiota composition,
      independent of age and carbohydrate or fat intake. The association between VO2max
      and EreC, however, appears to be mediated by body fatness.

PMID- 28757577
TI  - Schools, Air Pollution, and Active Transportation: An Exploratory Spatial
      Analysis of Calgary, Canada.
AB  - An exploratory spatial analysis investigates the location of schools in Calgary
      (Canada) in relation to air pollution and active transportation options. Air
      pollution exhibits marked spatial variation throughout the city, along with
      distinct spatial patterns in summer and winter; however, all school locations lie
      within low to moderate pollution levels. Conversely, the study shows that almost
      half of the schools lie in low walkability locations; likewise, transitability is
      low for 60% of schools, and only bikability is widespread, with 93% of schools in
      very bikable locations. School locations are subsequently categorized by
      pollution exposure and active transportation options. This analysis identifies
      and maps schools according to two levels of concern: schools in car-dependent
      locations and relatively high pollution; and schools in locations conducive of
      active transportation, yet exposed to relatively high pollution. The findings can
      be mapped and effectively communicated to the public, health practitioners, and
      school boards. The study contributes with an explicitly spatial approach to the
      intra-urban public health literature. Developed for a moderately polluted city,
      the methods can be extended to more severely polluted environments, to assist in
      developing spatial public health policies to improve respiratory outcomes,
      neurodevelopment, and metabolic and attention disorders in school-aged children.

PMID- 28757578
TI  - Grading of Chinese Cantonese Sausage Using Hyperspectral Imaging Combined with
      Chemometric Methods.
AB  - Fast and accurate grading of Chinese Cantonese sausage is an important concern
      for customers, organizations, and the industry. Hyperspectral imaging in the
      spectral range of 874-1734 nm, combined with chemometric methods, was applied to
      grade Chinese Cantonese sausage. Three grades of intact and sliced Cantonese
      sausages were studied, including the top, first, and second grades. Support
      vector machine (SVM) and random forests (RF) techniques were used to build two
      different models. Second derivative spectra and RF were applied to select optimal
      wavelengths. The optimal wavelengths were the same for intact and sliced sausages
      when selected from second derivative spectra, while the optimal wavelengths for
      intact and sliced sausages selected using RF were quite similar. The SVM and RF
      models, using full spectra and the optimal wavelengths, obtained acceptable
      results for intact and sliced sausages. Both models for intact sausages performed
      better than those for sliced sausages, with a classification accuracy of the
      calibration and prediction set of over 90%. The overall results indicated that
      hyperspectral imaging combined with chemometric methods could be used to grade
      Chinese Cantonese sausages, with intact sausages being better suited for grading.
      This study will help to develop fast and accurate online grading of Cantonese
      sausages, as well as other sausages.

PMID- 28757579
TI  - Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles.
AB  - Microbubbles-assisted ultrasound (USMB) has shown promise in improving local drug
      delivery. The formation of transient membrane pores and endocytosis are reported
      to be enhanced by USMB, and they contribute to cellular drug uptake. Exocytosis
      also seems to be linked to endocytosis upon USMB treatment. Based on this
      rationale, we investigated whether USMB triggers exocytosis resulting in the
      release of extracellular vesicles (EVs). USMB was performed on a monolayer of
      head-and-neck cancer cells (FaDu) with clinically approved microbubbles and
      commonly used ultrasound parameters. At 2, 4, and 24 h, cells and EV-containing
      conditioned media from USMB and control conditions (untreated cells, cells
      treated with microbubbles and ultrasound only) were harvested. EVs were measured
      using flow cytometric immuno-magnetic bead capture assay, immunogold electron
      microscopy, and western blotting. After USMB, levels of CD9 exposing-EVs
      significantly increased at 2 and 4 h, whereas levels of CD63 exposing-EVs
      increased at 2 h. At 24 h, EV levels were comparable to control levels. EVs
      released after USMB displayed a heterogeneous size distribution profile (30-1200
      nm). Typical EV markers CD9, CD63, and alix were enriched in EVs released from
      USMB-treated FaDu cells. In conclusion, USMB treatment triggers exocytosis
      leading to the release of EVs from FaDu cells.

PMID- 28757580
TI  - Role of Mitochondria and Endoplasmic Reticulum in Taurine-Deficiency-Mediated
      Apoptosis.
AB  - Taurine is a ubiquitous sulfur-containing amino acid found in high concentration
      in most tissues. Because of its involvement in fundamental physiological
      functions, such as regulating respiratory chain activity, modulating cation
      transport, controlling inflammation, altering protein phosphorylation and
      prolonging lifespan, taurine is an important nutrient whose deficiency leads to
      severe pathology and cell death. However, the mechanism by which taurine
      deficiency causes cell death is inadequately understood. Therefore, the present
      study examined the hypothesis that overproduction of reactive oxygen species
      (ROS) by complex I of the respiratory chain triggers mitochondria-dependent
      apoptosis in hearts of taurine transporter knockout (TauTKO) mice. In support of
      the hypothesis, a 60% decrease in mitochondrial taurine content of 3-month-old
      TauTKO hearts was observed, which was associated with diminished complex I
      activity and the onset of mitochondrial oxidative stress. Oxidative damage to
      stressed mitochondria led to activation of a caspase cascade, with stimulation of
      caspases 9 and 3 prevented by treatment of 3-month-old TauTKO mice with the
      mitochondria specific antioxidant, MitoTempo. In 12 month-old, but not 3-month
      old, TauTKO hearts, caspase 12 activation contributes to cell death, revealing a
      pathological role for endoplasmic reticulum (ER) stress in taurine deficient,
      aging mice. Thus, taurine is a cytoprotective nutrient that ensures normal
      mitochondrial and ER function, which is important for the reduction of risk for
      apoptosis and premature death.

PMID- 28757581
TI  - Identification of Urinary Polyphenol Metabolite Patterns Associated with
      Polyphenol-Rich Food Intake in Adults from Four European Countries.
AB  - We identified urinary polyphenol metabolite patterns by a novel algorithm that
      combines dimension reduction and variable selection methods to explain polyphenol
      rich food intake, and compared their respective performance with that of single
      biomarkers in the European Prospective Investigation into Cancer and Nutrition
      (EPIC) study. The study included 475 adults from four European countries
      (Germany, France, Italy, and Greece). Dietary intakes were assessed with 24-h
      dietary recalls (24-HDR) and dietary questionnaires (DQ). Thirty-four polyphenols
      were measured by ultra-performance liquid chromatography-electrospray ionization
      tandem mass spectrometry (UPLC-ESI-MS-MS) in 24-h urine. Reduced rank regression
      based variable importance in projection (RRR-VIP) and least absolute shrinkage
      and selection operator (LASSO) methods were used to select polyphenol
      metabolites. Reduced rank regression (RRR) was then used to identify patterns in
      these metabolites, maximizing the explained variability in intake of pre-selected
      polyphenol-rich foods. The performance of RRR models was evaluated using internal
      cross-validation to control for over-optimistic findings from over-fitting. High
      performance was observed for explaining recent intake (24-HDR) of red wine (r =
      0.65; AUC = 89.1%), coffee (r = 0.51; AUC = 89.1%), and olives (r = 0.35; AUC =
      82.2%). These metabolite patterns performed better or equally well compared to
      single polyphenol biomarkers. Neither metabolite patterns nor single biomarkers
      performed well in explaining habitual intake (as reported in the DQ) of
      polyphenol-rich foods. This proposed strategy of biomarker pattern identification
      has the potential of expanding the currently still limited list of available
      dietary intake biomarkers.

PMID- 28757584
TI  - New Matching Method for Accelerometers in Gravity Gradiometer.
AB  - The gravity gradiometer is widely used in mineral prospecting, including in the
      exploration of mineral, oil and gas deposits. The mismatch of accelerometers
      adversely affects the measuring precision of rotating accelerometer-based gravity
      gradiometers. Several strategies have been investigated to address the imbalance
      of accelerometers in gradiometers. These strategies, however, complicate
      gradiometer structures because feedback loops and re-designed accelerometers are
      needed in these strategies. In this paper, we present a novel matching method,
      which is based on a new configuration of accelerometers in a gravity gradiometer.
      In the new configuration, an angle was introduced between the measurement
      direction of the accelerometer and the spin direction. With the introduced angle,
      accelerometers could measure the centrifugal acceleration generated by the
      rotating disc. Matching was realized by updating the scale factors of the
      accelerometers with the help of centrifugal acceleration. Further simulation
      computations showed that after adopting the new matching method, signal-to-noise
      ratio improved from -41 dB to 22 dB. Compared with other matching methods, our
      method is more flexible and costs less. The matching accuracy of this new method
      is similar to that of other methods. Our method provides a new idea for matching
      methods in gravity gradiometer measurement.

PMID- 28757582
TI  - Lactacystin-Induced Model of Hypertension in Rats: Effects of Melatonin and
      Captopril.
AB  - Lactacystin is a proteasome inhibitor that interferes with several factors
      involved in heart remodelling. The aim of this study was to investigate whether
      the chronic administration of lactacystin induces hypertension and heart
      remodelling and whether these changes can be modified by captopril or melatonin.
      In addition, the lactacystin-model was compared with NG-nitro-l-arginine-methyl
      ester (L-NAME)- and continuous light-induced hypertension. Six groups of three
      month-old male Wistar rats (11 per group) were treated for six weeks as follows:
      control (vehicle), L-NAME (40 mg/kg/day), continuous light (24 h/day),
      lactacystin (5 mg/kg/day) alone, and lactacystin with captopril (100 mg/kg/day),
      or melatonin (10 mg/kg/day). Lactacystin treatment increased systolic blood
      pressure (SBP) and induced fibrosis of the left ventricle (LV), as observed in L
      NAME-hypertension and continuous light-hypertension. LV weight and the cross
      sectional area of the aorta were increased only in L-NAME-induced hypertension.
      The level of oxidative load was preserved or reduced in all three models of
      hypertension. Nitric oxide synthase (NOS) activity in the LV and kidney was
      unchanged in the lactacystin group. Nuclear factor-kappa B (NF-kappaB) protein
      expression in the LV was increased in all treated groups in the cytoplasm,
      however, in neither group in the nucleus. Although melatonin had no effect on
      SBP, only this indolamine (but not captopril) reduced the concentration of
      insoluble and total collagen in the LV and stimulated the NO-pathway in the
      lactacystin group. We conclude that chronic administration of lactacystin
      represents a novel model of hypertension with collagenous rebuilding of the LV,
      convenient for testing antihypertensive drugs or agents exerting a cardiovascular
      benefit beyond blood pressure reduction.

PMID- 28757586
TI  - Application of Nanosize Zeolite Molecular Sieves for Medical Oxygen
      Concentration.
AB  - The development of a portable oxygen concentrator is of prime significance for
      patients with respiratory problems. This paper presents a portable concentrator
      prototype design using the pressure/vacuum swing adsorption (PVSA) cycle with a
      deep evacuation step (-0.82 barg) instead of desorption with purge flow to
      simplify the oxygen production process. The output of the oxygen concentrator is
      a ~90 vol % enriched oxygen stream in a continuous adsorption and desorption
      cycle (cycle time ~90 s). The size of the adsorption column is 3 cm in diameter
      and 20 cm in length. A Li+ exchanged 13X nanosize zeolite is used as the
      adsorbent to selectively adsorb nitrogen from air. A dynamic model of the
      pressure and vacuum swing adsorption units was developed to study the
      pressurization and depressurization process inside the microporous area of
      nanosized zeolites. The describing equations were solved using COMSOL
      Multiphysics Chemical Engineering module. The output flow rate and oxygen
      concentration results from the simulation model were compared with the
      experimental data. Velocity and concentration profiles were obtained to study the
      adsorption process and optimize the operational parameters.

PMID- 28757583
TI  - Chalcone Derivatives: Promising Starting Points for Drug Design.
AB  - Medicinal chemists continue to be fascinated by chalcone derivatives because of
      their simple chemistry, ease of hydrogen atom manipulation, straightforward
      synthesis, and a variety of promising biological activities. However, chalcones
      have still not garnered deserved attention, especially considering their high
      potential as chemical sources for designing and developing new effective drugs.
      In this review, we summarize current methodological developments towards the
      design and synthesis of new chalcone derivatives and state-of-the-art medicinal
      chemistry strategies (bioisosterism, molecular hybridization, and pro-drug
      design). We also highlight the applicability of computer-assisted drug design
      approaches to chalcones and address how this may contribute to optimizing
      research outputs and lead to more successful and cost-effective drug discovery
      endeavors. Lastly, we present successful examples of the use of chalcones and
      suggest possible solutions to existing limitations.

PMID- 28757585
TI  - Should Research on the Nutritional Potential and Health Benefits of Fermented
      Cereals Focus More on the General Health Status of Populations in Developing
      Countries?
AB  - Cereal foods fermented by lactic acid bacteria are staples in many countries
      around the world particularly in developing countries, but some aspects of the
      nutritional and health benefits of traditional fermented foods in developing
      countries have not been sufficiently investigated compared to fermented foods in
      high-income countries. Today, malnutrition worldwide is characterized by a double
      burden, excess leading to non-communicable diseases like obesity or diabetes
      alongside micronutrient deficiencies. In addition, populations in developing
      countries suffer from infectious and parasitic diseases that can jeopardize the
      health benefits provided by their traditional fermented foods. Using examples, we
      argue that research on traditional fermented cereals in developing countries
      should focus more on their effect on inflammation and oxidative stress under
      conditions including infectious or non-infectious gut inflammation.

PMID- 28757587
TI  - Recent Advancements towards Full-System Microfluidics.
AB  - Microfluidics is quickly becoming a key technology in an expanding range of
      fields, such as medical sciences, biosensing, bioactuation, chemical synthesis,
      and more. This is helping its transformation from a promising R&D tool to
      commercially viable technology. Fuelling this expansion is the intensified focus
      on automation and enhanced functionality through integration of complex
      electrical control, mechanical properties, in situ sensing and flow control. Here
      we highlight recent contributions to the Sensors Special Issue series called
      "Microfluidics-Based Microsystem Integration Research" under the following
      categories: (i) Device fabrication to support complex functionality; (ii) New
      methods for flow control and mixing; (iii) Towards routine analysis and point of
      care applications; (iv) In situ characterization; and (v) Plug and play
      microfluidics.

PMID- 28757588
TI  - Complexation-Based Detection of Nickel(II) at a Graphene-Chelate Probe in the
      Presence of Cobalt and Zinc by Adsorptive Stripping Voltammetry.
AB  - The adsorptive stripping voltammetric detection of nickel and cobalt in water
      samples at metal film electrodes has been extensively studied. In this work, a
      novel, environmentally friendly, metal-free electrochemical probe was constructed
      for the ultra-trace determination of Ni2+ in water samples by Adsorptive Cathodic
      Stripping Voltammetry (AdCSV). The electrochemical platform is based on the
      adsorptive accumulation of Ni2+ ions directly onto a glassy carbon electrode
      (GCE) modified with dimethylglyoxime (DMG) as chelating agent and a Nafion
      graphene (NGr) nanocomposite to enhance electrode sensitivity. The nafion
      graphene dimethylglyoxime modified glassy carbon electrode (NGr-DMG-GCE) shows
      superior detection capabilities as a result of the improved surface-area-to
      volume ratio and enhanced electron transfer kinetics following the incorporation
      of single layer graphene, while limiting the toxic effects of the sensor by
      removal of the more common mercury, bismuth and lead films. Furthermore, for the
      first time the NGr-DMG-GCE, in the presence of common interfering metal ions of
      Co2+ and Zn2+ demonstrates good selectivity and preferential binding towards the
      detection of Ni2+ in water samples. Structural and morphological characterisation
      of the synthesised single layer graphene sheets was conducted by Raman
      spectrometry, HRTEM and HRSEM analysis. The instrumental parameters associated
      with the electrochemical response, including accumulation potential and
      accumulation time were investigated and optimised in addition to the influence of
      DMG and graphene concentrations. The NGr-DMG-GCE demonstrated well resolved,
      reproducible peaks, with RSD (%) below 5% and a detection limit of 1.5 ug L-1 for
      Ni2+ reduction at an accumulation time of 120 s., the prepared electrochemical
      sensor exhibited good detection and quantitation towards Ni2+ detection in tap
      water samples, well below 0.1 mg L-1 set by the WHO and EPA standards. This
      comparable to the South African drinking water guidelines of 0.15 mg L-1.

PMID- 28757589
TI  - Influence of Socioeconomic Status on Knowledge of Obesity and Diabetes among
      Adolescents in Chennai, South India.
AB  - The Obesity Reduction and Awareness of Non-communicable disease through Group
      Education (ORANGE) Phase II program, is a school-based intervention aimed at
      healthy lifestyle practices for sixth and seventh grade adolescents (n = 2345)
      attending private (n = 1811) and government (n = 534) schools in Chennai. The
      objectives of this paper are (a) to describe the intervention activities and
      their outcomes qualitatively and (b) to report changes in body mass index (BMI)
      of the intervention group participants. This intervention strategy used a teacher
      peer-training model in each school for long-term sustainability of the lessons
      learned from this program. During each intervention session, teachers led a
      classroom discussion on the health topic of interest, and peers facilitated small
      group learning activities. Anthropometric measurements of participants were
      assessed pre- and post-intervention. We found government school students
      perceived hygienic actions (e.g., drinking clean water, taking baths daily) as
      healthy habits for preventing diabetes, whereas private school students
      associated an expensive lifestyle (e.g., eating at restaurants, riding a car)
      with diabetes prevention. Overall, the mean post-intervention BMI (18.3 kg/m2)
      was in the normal range compared to the pre-intervention BMI (17.7 kg/m2) (p <
      0.0001). These results suggest that future interventions should be tailored for
      adolescents from different socio-economic groups while acknowledging their varied
      perceptions.

PMID- 28757590
TI  - Tanshinone IIA Inhibits Epithelial-Mesenchymal Transition in Bladder Cancer Cells
      via Modulation of STAT3-CCL2 Signaling.
AB  - Tanshinone IIA (Tan-IIA) is an extract from the widely used traditional Chinese
      medicine (TCM) Danshen (Salvia miltiorrhiza), and has been found to attenuate the
      proliferation of bladder cancer (BCa) cells (The IC50 were: 5637, 2.6 MUg/mL;
      BFTC, 2 MUg/mL; T24, 2.7 MUg/mL, respectively.). However, the mechanism of the
      effect of Tan-IIA on migration inhibition of BCa cells remains unclear. This
      study investigates the anti-metastatic effect of Tan-IIA in human BCa cells and
      clarifies its molecular mechanism. Three human BCa cell lines, 5637, BFTC and
      T24, were used for subsequent experiments. Cell migration and invasion were
      evaluated by transwell assays. Real-time RT-PCR and western blotting were
      performed to detect epithelial-mesenchymal transition (EMT)-related gene
      expression. The enzymatic activity of matrix metalloproteinases (MMP) was
      evaluated by zymography assay. Tan-IIA inhibited the migration and invasion of
      human BCa cells. Tan-IIA suppressed both the protein expression and enzymatic
      activity of MMP-9/-2 in human BCa cells. Tan-IIA up-regulated the epithelial
      marker E-cadherin and down-regulated mesenchymal markers such as N-cadherin and
      Vimentin, along with transcription regulators such as Snail and Slug in BCa cells
      in a time- and dose-dependent manner. Mechanism dissection revealed that Tan-IIA
      inhibited BCa cell invasion could function via suppressed chemokine (C-C motif)
      ligand 2 (CCL2) expression, which could be reversed by the addition of CCL2
      recombinant protein. Furthermore, Tan-IIA could inhibit the phosphorylation of
      the signal transducer and activator of transcription 3 (STAT3) (Tyr705), which
      cannot be restored by the CCL2 recombinant protein addition. These data
      implicated that Tan-IIA might suppress EMT on BCa cells through STAT3-CCL2
      signaling inhibition. Tan-IIA inhibits EMT of BCa cells via modulation of STAT3
      CCL2 signaling. Our findings suggest that Tan-IIA can serve as a potential anti
      metastatic agent in BCa therapy.

PMID- 28757592
TI  - Analysis of the Optimum Gain of a High-Pass L-Matching Network for Rectennas.
AB  - Rectennas, which mainly consist of an antenna, matching network, and rectifier,
      are used to harvest radiofrequency energy in order to power tiny sensor nodes,
      e.g., the nodes of the Internet of Things. This paper demonstrates for the first
      time, the existence of an optimum voltage gain for high-pass L-matching networks
      used in rectennas by deriving an analytical expression. The optimum gain is that
      which leads to maximum power efficiency of the rectenna. Here, apart from the L
      matching network, a Schottky single-diode rectifier was used for the rectenna,
      which was optimized at 868 MHz for a power range from -30 dBm to -10 dBm. As the
      theoretical expression depends on parameters not very well-known a priori, an
      accurate search of the optimum gain for each power level was performed via
      simulations. Experimental results show remarkable power efficiencies ranging from
      16% at -30 dBm to 55% at -10 dBm, which are for almost all the tested power
      levels the highest published in the literature for similar designs.

PMID- 28757591
TI  - Notch Signaling in Endothelial Cells: Is It the Therapeutic Target for Vascular
      Neointimal Hyperplasia?
AB  - Blood vessels respond to injury through a healing process that includes
      neointimal hyperplasia. The vascular endothelium is a monolayer of cells that
      separates the outer vascular wall from the inner circulating blood. The
      disruption and exposure of endothelial cells (ECs) to subintimal components
      initiate the neointimal formation. ECs not only act as a highly selective barrier
      to prevent early pathological changes of neointimal hyperplasia, but also
      synthesize and release molecules to maintain vascular homeostasis. After vascular
      injury, ECs exhibit varied responses, including proliferation, regeneration,
      apoptosis, phenotypic switching, interacting with other cells by direct contact
      or secreted molecules and the change of barrier function. This brief review
      presents the functional role of the evolutionarily-conserved Notch pathway in
      neointimal hyperplasia, notably by regulating endothelial cell functions
      (proliferation, regeneration, apoptosis, differentiation, cell-cell interaction).
      Understanding endothelial cell biology should help us define methods to prompt
      cell proliferation, prevent cell apoptosis and dysfunction, block neointimal
      hyperplasia and vessel narrowing.

PMID- 28757594
TI  - High Constitutive Overexpression of Glycosyl Hydrolase Family 17 Delays Floral
      Transition by Enhancing FLC Expression in Transgenic Arabidopsis.
AB  - Vitis vinifera glycosyl hydrolase family 17 (VvGHF17) is a grape apoplasmic beta
      1,3-glucanase, which belongs to glycosyl hydrolase family 17 in grapevines. beta
      1,3-glucanase is not only involved in plant defense response but also has various
      physiological functions in plants. Although VvGHF17 expression is negatively
      related to the length of inflorescence in grapevines, the physiological functions
      of VvGHF17 are still uncertain. To clarify the physiological functions of
      VvGHF17, we conducted a phenotypic analysis of VvGHF17-overexpressing Arabidopsis
      plants. VvGHF17-overexpressing Arabidopsis plants showed short inflorescence,
      similar to grapevines. These results suggested that VvGHF17 might negatively
      regulate the length of inflorescence in plants. VvGHF17 expression induced a
      delay of floral transition in Arabidopsis plants. The expression level of
      FLOWERING LOCUS C (FLC), known as a floral repressor gene, in inflorescence
      meristem of transgenic plants were increased by approximately 10-fold as compared
      with wild plants. These results suggest that VvGHF17 induces a delay of floral
      transition by enhancing FLC expression and concomitantly decreases the length of
      plant inflorescence.

PMID- 28757593
TI  - Sechium edule (Jacq.) Swartz, a New Cultivar with Antiproliferative Potential in
      a Human Cervical Cancer HeLa Cell Line.
AB  - The Sechium edule Perla Negra cultivar is a recently-obtained biological material
      whose progenitors are S. edule var. nigrum minor and S. edule var. amarus
      silvestrys, the latter of which has been reported to have antiproliferative
      activity against the HeLa P-388 and L-929 cancer cell lines. The present study
      aimed to determine if the methanolic extract of the fruit of the Perla Negra
      cultivar had the same biological activity. The methanolic extract was
      phytochemically characterized by thin layer chromatography (TLC) and column
      chromatography (CC), identifying the terpenes and flavonoids. The compounds
      identified via high performance liquid chromatography (HPLC) were Cucurbitacins
      B, D, E, and I for the terpene fractions, and Rutin, Phlorizidin, Myricetin,
      Quercetin, Naringenin, Phloretin, Apigenin, and Galangin for the flavonoid
      fractions). Biological activity was evaluated with different concentrations of
      the methanolic extract in the HeLa cell line and normal lymphocytes. The
      methanolic extract inhibited the proliferation of HeLa cells (IC50 1.85 ug.mL-1),
      but the lymphocytes were affected by the extract (IC50 30.04 ug.mL-1). Some
      fractions, and the pool of all of them, showed inhibition higher than 80% at a
      concentration of 2.11 ug.mL-1. Therefore, the biological effect shown by the
      methanolic extract of the Perla Negra has some specificity in inhibiting tumor
      cells and not normal cells; an unusual feature among molecules investigated as
      potential biomedical agents.

PMID- 28757595
TI  - Early Marriage and Barriers to Contraception among Syrian Refugee Women in
      Lebanon: A Qualitative Study.
AB  - The Syrian conflict has displaced five million individuals outside their country
      with Lebanon hosting the largest numbers per capita. Around 24% of Syrian
      refugees fleeing to Lebanon are women of reproductive age (15-49). Yet, a better
      understanding of the sexual and reproductive health needs of Syrian refugee women
      in Lebanon is required to improve provided services. Eleven focus group
      discussions were conducted in four regions of Lebanon with 108 Syrian refugee
      women of reproductive age. Thematic analysis was used to examine the data.
      Interviewed women were mainly adults. They believed that, in Lebanon, they were
      subjected to early marriage compared to the norm in Syria due to their financial
      situation and uncertainty. Cost was reported as the main barrier to use
      contraception in Lebanon but some Syrian refugee women were not aware of free
      services covering sexual and reproductive health. In general, marriage,
      pregnancy, and family planning behavior of Syrian refugee women in Lebanon
      slightly differed from those in Syria pre-conflict in terms of age of marriage,
      conception subsequent to marriage, and contraception method. Hence, interventions
      to increase awareness of subsidized sexual and reproductive health services,
      including free contraceptives at primary health care centers, and those targeting
      protection from early marriage of Syrian refugee women in Lebanon are strongly
      recommended.

PMID- 28757596
TI  - Structural Characterization of Cholestane Rhamnosides from Ornithogalum
      saundersiae Bulbs and Their Cytotoxic Activity against Cultured Tumor Cells.
AB  - Previous phytochemical studies of the bulbs of Ornithogalum saundersiae, an
      ornamental perennial plant native to South Africa, resulted in the isolation of
      29 new cholestane glycosides, some of which were structurally unique and showed
      potent cytotoxic activity against cultured tumor cell lines. Therefore, we aimed
      to perform further phytochemical examinations of methanolic extracts obtained
      from Ornithogalum saundersiae bulbs, isolating 12 new cholestane rhamnosides (1
      12) and seven known compounds (13-19). The structures of the new compounds (1-12)
      were identified via NMR-based structural characterization methods, and through a
      sequence of chemical transformations followed by spectroscopic and
      chromatographic analysis. The cytotoxic activity of the isolated compounds (1-19)
      and the derivatives (1a and 6a) against HL-60 human promyelocytic leukemia cells
      and A549 human lung adenocarcinoma cells was evaluated. Compounds 10-12, 16, and
      17 showed cytotoxicity against both HL-60 and A549 cells. Compound 11 showed
      potent cytotoxicity with an IC50 value of 0.16 uM against HL-60 cells and induced
      apoptotic cell death via a mitochondrion-independent pathway.

PMID- 28757597
TI  - Statins, Muscle Disease and Mitochondria.
AB  - Cardiovascular disease (CVD) accounts for >17 million deaths globally every year,
      and this figure is predicted to rise to >23 million by 2030. Numerous studies
      have explored the relationship between cholesterol and CVD and there is now
      consensus that dyslipidaemia is a causal factor in the pathogenesis of
      atherosclerosis. Statins have become the cornerstone of the management of
      dyslipidaemia. Statins have proved to have a very good safety profile. The risk
      of adverse events is small compared to the benefits. Nevertheless, the potential
      risk of an adverse event occurring must be considered when prescribing and
      monitoring statin therapy to individual patients. Statin-associated muscle
      disease (SAMS) is by far the most studied and the most common reason for
      discontinuation of therapy. The reported incidence varies greatly, ranging
      between 5% and 29%. Milder disease is common and the more serious form,
      rhabdomyolysis is far rarer with an incidence of approximately 1 in 10,000. The
      pathophysiology of, and mechanisms leading to SAMS, are yet to be fully
      understood. Literature points towards statin-induced mitochondrial dysfunction as
      the most likely cause of SAMS. However, the exact processes leading to
      mitochondrial dysfunction are not yet fully understood. This paper details some
      of the different aetiological hypotheses put forward, focussing particularly on
      those related to mitochondrial dysfunction.

PMID- 28757599
TI  - Different Metabolic Pathways Are Involved in Response of Saccharomyces cerevisiae
      to L-A and M Viruses.
AB  - Competitive and naturally occurring yeast killer phenotype is governed by
      coinfection with dsRNA viruses. Long-term relationship between the host cell and
      viruses appear to be beneficial and co-adaptive; however, the impact of viral
      dsRNA on the host gene expression has barely been investigated. Here, we
      determined the transcriptomic profiles of the host Saccharomyces cerevisiae upon
      the loss of the M-2 dsRNA alone and the M-2 along with the L-A-lus dsRNAs. We
      provide a comprehensive study based on the high-throughput RNA-Seq data, Gene
      Ontology and the analysis of the interaction networks. We identified 486 genes
      differentially expressed after curing yeast cells of the M-2 dsRNA and 715 genes
      affected by the elimination of both M-2 and L-A-lus dsRNAs. We report that most
      of the transcriptional responses induced by viral dsRNAs are moderate.
      Differently expressed genes are related to ribosome biogenesis, mitochondrial
      functions, stress response, biosynthesis of lipids and amino acids. Our study
      also provided insight into the virus-host and virus-virus interplays.

PMID- 28757601
TI  - Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Center
      Experience of Two Cases.
AB  - BACKGROUND Recurrent respiratory papillomatosis (RRP), caused by human
      papillomavirus (HPV), is the most common benign neoplasm of the larynx and
      central airways. RRP has a significant impact on quality life and high annual
      costs to healthcare. Currently, there is no cure for RRP, leading to repeated
      debulking operations for symptomatic palliation. Various local adjuvant therapies
      have also been studied with mixed efficacy. HPV oncogene products increase
      expression of vascular endothelial growth factor (VEGF) providing a potential
      target for treatment of RRP. Bevacizumab, a recombinant monoclonal antibody that
      inhibits VEGF, has shown efficacy in patients with localized disease. CASE REPORT
      We present two cases of extensive airway and parenchymal RRP successfully managed
      with systemically administered bevacizumab, a recombinant monoclonal antibody
      that inhibits VEGF. CONCLUSIONS Bevacizumab has shown efficacy in patients with
      localized disease, but here we illustrate the potential of bevacizumab for
      patients with extensive parenchymal burden as well as provide a brief review of
      the literature.

PMID- 28757598
TI  - Selective Serotonin Reuptake Inhibitors for Treating Neurocognitive and
      Neuropsychiatric Disorders Following Traumatic Brain Injury: An Evaluation of
      Current Evidence.
AB  - The prevalence of neuropsychiatric disorders following traumatic brain injury
      (TBI) is 20%-50%, and disorders of mood and cognition may remain even after
      recovery of neurologic function is achieved. Selective serotonin reuptake
      inhibitors (SSRI) block the reuptake of serotonin in presynaptic cells to lead to
      increased serotonergic activity in the synaptic cleft, constituting first-line
      treatment for a variety of neurocognitive and neuropsychiatric disorders. This
      review investigates the utility of SSRIs in treating post-TBI disorders. In
      total, 37 unique reports were consolidated from the Cochrane Central Register and
      PubMed (eight randomized-controlled trials (RCTs), nine open-label studies, 11
      case reports, nine review articles). SSRIs are associated with improvement of
      depressive but not cognitive symptoms. Pooled analysis using the Hamilton
      Depression Rating Scale demonstrate a significant mean decrease of depression
      severity following sertraline compared to placebo-a result supported by several
      other RCTs with similar endpoints. Evidence from smaller studies demonstrates
      mood improvement following SSRI administration with absent or negative effects on
      cognitive and functional recovery. Notably, studies on SSRI treatment effects for
      post-traumatic stress disorder after TBI remain absent, and this represents an
      important direction of future research. Furthermore, placebo-controlled studies
      with extended follow-up periods and concurrent biomarker, neuroimaging and
      behavioral data are necessary to delineate the attributable pharmacological
      effects of SSRIs in the TBI population.

PMID- 28757600
TI  - Relative Computed Tomography (CT) Enhancement Value for the Assessment of
      Microvascular Architecture in Renal Cell Carcinoma.
AB  - BACKGROUND To investigate the correlation between the relative computed
      tomography (CT) enhancement value and the microvascular architecture in different
      pathologic subtypes of renal cell carcinoma (RCC). MATERIAL AND METHODS This
      retrospective study included 55 patients with pathologically confirmed RCC.
      Immunohistochemistry for CD34 was performed for all surgical specimens.
      Microvascular architecture parameters (density, area, diameter, and perimeter)
      for the microvessels and the microvessels with lumen were determined. The CT scan
      was performed during arterial phase or venous phase. The correlation of
      parameters on CT and tumor angiogenesis was investigated. RESULTS Density of
      microvessels showed a positive correlation with CT values of tumors, ratios of
      tumor to cortex, and differences of tumor and medulla, but no correlation with CT
      value ratio of tumor to aorta or tumor to medulla. CT parameters were positively
      correlated with microvascular parameters. However, no CT parameter differences
      between hypo-vascular clear cell RCC and papillary RCC was observed. Strikingly,
      the density and area of the microvessels were significantly higher in hypo
      vascular clear cell RCC than that in papillary RCC, while the density of the
      microvessels with lumen in the cyst-present RCC was significantly higher than
      that in the cyst-absent RCC. The values (especially those of microvessels with
      lumen) of area density, diameter, and perimeter were higher in the capsule-absent
      RCC than in the capsule-present RCC. CONCLUSIONS The relative CT enhancement
      value of RCC was associated with vascular architecture parameters including
      density, area, and perimeter. Quantitative and semi-quantitative parameters on
      enhanced CT may shed some light on tumor vasculature and function as indicators
      of the biological behavior of RCC.

PMID- 28757602
TI  - Major agricultural changes required to mitigate phosphorus losses under climate
      change.
AB  - Phosphorus losses from land to water will be impacted by climate change and land
      management for food production, with detrimental impacts on aquatic ecosystems.
      Here we use a unique combination of methods to evaluate the impact of projected
      climate change on future phosphorus transfers, and to assess what scale of
      agricultural change would be needed to mitigate these transfers. We combine novel
      high-frequency phosphorus flux data from three representative catchments across
      the UK, a new high-spatial resolution climate model, uncertainty estimates from
      an ensemble of future climate simulations, two phosphorus transfer models of
      contrasting complexity and a simplified representation of the potential
      intensification of agriculture based on expert elicitation from land managers. We
      show that the effect of climate change on average winter phosphorus loads
      (predicted increase up to 30% by 2050s) will be limited only by large-scale
      agricultural changes (e.g., 20-80% reduction in phosphorus inputs).The impact of
      climate change on phosphorus (P) loss from land to water is unclear. Here, the
      authors use P flux data, climate simulations and P transfer models to show that
      only large scale agricultural change will limit the effect of climate change on
      average winter P loads in three catchments across the UK.

PMID- 28757605
TI  - The pros and cons of dying tumour cells in adaptive immune responses.

PMID- 28757606
TI  - Turning the light on.

PMID- 28757603
TI  - The regulation of immune tolerance by FOXP3.
AB  - The proper restraint of the destructive potential of the immune system is
      essential for maintaining health. Regulatory T (Treg) cells ensure immune
      homeostasis through their defining ability to suppress the activation and
      function of other leukocytes. The expression of the transcription factor forkhead
      box protein P3 (FOXP3) is a well-recognized characteristic of Treg cells, and
      FOXP3 is centrally involved in the establishment and maintenance of the Treg cell
      phenotype. In this Review, we summarize how the expression and activity of FOXP3
      are regulated across multiple layers by diverse factors. The therapeutic
      implications of these topics for cancer and autoimmunity are also discussed.

PMID- 28757604
TI  - Mechanical forces in the immune system.
AB  - Leukocytes can completely reorganize their cytoskeletal architecture within
      minutes. This structural plasticity, which facilitates their migration and
      communicative function, also enables them to exert a substantial amount of
      mechanical force against the extracellular matrix and the surfaces of interacting
      cells. In recent years, it has become increasingly clear that these forces have
      crucial roles in immune cell activation and subsequent effector responses. Here,
      I review our current understanding of how mechanical force regulates cell-surface
      receptor activation, cell migration, intracellular signalling and intercellular
      communication, highlighting the biological ramifications of these effects in
      various immune cell types.

PMID- 28757608
TI  - The elegance of a macrophage.

PMID- 28757607
TI  - Ubiquitination of stalled ribosome triggers ribosome-associated quality control.
AB  - Translation arrest by polybasic sequences induces ribosome stalling, and the
      arrest product is degraded by the ribosome-mediated quality control (RQC) system.
      Here we report that ubiquitination of the 40S ribosomal protein uS10 by the E3
      ubiquitin ligase Hel2 (or RQT1) is required for RQC. We identify a RQC-trigger
      (RQT) subcomplex composed of the RNA helicase-family protein Slh1/Rqt2, the
      ubiquitin-binding protein Cue3/Rqt3, and yKR023W/Rqt4 that is required for RQC.
      The defects in RQC of the RQT mutants correlate with sensitivity to anisomycin,
      which stalls ribosome at the rotated form. Cryo-electron microscopy analysis
      reveals that Hel2-bound ribosome are dominantly the rotated form with hybrid
      tRNAs. Ribosome profiling reveals that ribosomes stalled at the rotated state
      with specific pairs of codons at P-A sites serve as RQC substrates. Rqt1
      specifically ubiquitinates these arrested ribosomes to target them to the RQT
      complex, allowing subsequent RQC reactions including dissociation of the stalled
      ribosome into subunits.Several protein quality control mechanisms are in place to
      trigger the rapid degradation of aberrant polypeptides and mRNAs. Here the
      authors describe a mechanism of ribosome-mediated quality control that involves
      the ubiquitination of ribosomal proteins by the E3 ubiquitin ligase Hel2/RQT1.

PMID- 28757609
TI  - Message in a bottle from the tumor microenvironment: tumor-educated DCs instruct
      B cells to participate in immunosuppression.

PMID- 28757611
TI  - Gut microbiota metabolites for sweetening type I diabetes.

PMID- 28757610
TI  - The IL-1R/TLR signaling pathway is essential for efficient CD8+ T-cell responses
      against hepatitis B virus in the hydrodynamic injection mouse model.
AB  - The outcome of hepatitis B viral (HBV) infection is determined by the complex
      interactions between replicating HBV and the immune system. While the role of the
      adaptive immune system in the resolution of HBV infection has been studied
      extensively, the contribution of innate immune mechanisms remains to be defined.
      Here we examined the role of the interleukin-1 receptor/Toll-like receptor (IL
      1R/TLR) signaling pathway in adaptive immune responses and viral clearance by
      exploring the HBV mouse model. Hydrodynamic injection with a replication
      competent HBV genome was performed in wild-type mice (WT) and a panel of mouse
      strains lacking specific innate immunity component expression. We found higher
      levels of HBV protein production and replication in Tlr2-/-, Tlr23479-/-,
      3d/Tlr24-/-, Myd88/Trif-/- and Irak4-/- mice, which was associated with reduced
      HBV-specific CD8+ T-cell responses in these mice. Importantly, HBV clearance was
      delayed for more than 2 weeks in 3d/Tlr24-/-, Myd88/Trif-/- and Irak4-/- mice
      compared to WT mice. HBV-specific CD8+ T-cell responses were functionally
      impaired for producing the cytokines IFN-gamma, TNF-alpha and IL-2 in TLR
      signaling-deficient mice compared to WT mice. In conclusion, the IL-1R/TLR
      signaling pathway might contribute to controlling HBV infection by augmenting HBV
      specific CD8+ T-cell responses.

PMID- 28757612
TI  - The CD24-Siglec G axis protects mice against cuprizone-induced oligodendrocyte
      loss: targeting danger signal for neuroprotection.

PMID- 28757613
TI  - Multilayer epigenetic analysis reveals novel transcription factor networks in CD8
      T cells.

PMID- 28757614
TI  - High-level intrinsic disorder explains the universality of CLIP binding to
      diverse MHC class II variants.

PMID- 28757616
TI  - Is there a pressing need for improving prognostication strategies in therapy
      related myelodysplastic syndromes?
AB  - Leukemia accepted article preview online, 31 July 2017. doi:10.1038/leu.2017.237.

PMID- 28757615
TI  - RORalpha controls hepatic lipid homeostasis via negative regulation of PPARgamma
      transcriptional network.
AB  - The retinoic acid receptor-related orphan receptor-alpha (RORalpha) is an
      important regulator of various biological processes, including cerebellum
      development, circadian rhythm and cancer. Here, we show that hepatic RORalpha
      controls lipid homeostasis by negatively regulating transcriptional activity of
      peroxisome proliferators-activated receptor-gamma (PPARgamma) that mediates
      hepatic lipid metabolism. Liver-specific Roralpha-deficient mice develop hepatic
      steatosis, obesity and insulin resistance when challenged with a high-fat diet
      (HFD). Global transcriptome analysis reveals that liver-specific deletion of
      Roralpha leads to the dysregulation of PPARgamma signaling and increases hepatic
      glucose and lipid metabolism. RORalpha specifically binds and recruits histone
      deacetylase 3 (HDAC3) to PPARgamma target promoters for the transcriptional
      repression of PPARgamma. PPARgamma antagonism restores metabolic homeostasis in
      HFD-fed liver-specific Roralpha deficient mice. Our data indicate that RORalpha
      has a pivotal role in the regulation of hepatic lipid homeostasis. Therapeutic
      strategies designed to modulate RORalpha activity may be beneficial for the
      treatment of metabolic disorders.Hepatic steatosis development may result from
      dysregulation of lipid metabolism, which is finely tuned by several transcription
      factors including the PPAR family. Here Kim et al. show that the nuclear receptor
      RORalpha inhibits PPARgamma-mediated transcriptional activity by interacting with
      HDAC3 and competing for the promoters of lipogenic genes.

PMID- 28757617
TI  - Nilotinib-induced vasculopathy: identification of vascular endothelial cells as a
      primary target site.
AB  - The BCR/ABL1 inhibitor Nilotinib is increasingly used to treat patients with
      chronic myeloid leukemia (CML). Although otherwise well-tolerated, Nilotinib has
      been associated with the occurrence of progressive arterial occlusive disease
      (AOD). Our objective was to determine the exact frequency of AOD and examine in
      vitro and in vivo effects of Nilotinib and Imatinib on endothelial cells to
      explain AOD-development. In contrast to Imatinib, Nilotinib was found to
      upregulate pro-atherogenic adhesion-proteins (ICAM-1, E-selectin, VCAM-1) on
      human endothelial cells. Nilotinib also suppressed endothelial cell
      proliferation, migration and tube-formation and bound to a distinct set of target
      kinases, relevant to angiogenesis and atherosclerosis, including angiopoietin
      receptor-1 TEK, ABL-2, JAK1 and MAP-kinases. Nilotinib and siRNA against ABL-2
      also suppressed KDR expression. In addition, Nilotinib augmented atherosclerosis
      in ApoE-/- mice and blocked reperfusion and angiogenesis in a hindlimb-ischemia
      model of arterial occlusion, whereas Imatinib showed no comparable effects.
      Clinically overt AOD-events were found to accumulate over time in Nilotinib
      treated patients. After a median observation-time of 2.0 years, the AOD-frequency
      was higher in these patients (29.4%) compared to risk factor- and age-matched
      controls (<5%). Together, Nilotinib exerts direct pro-atherogenic and anti
      angiogenic effects on vascular endothelial cells, which may contribute to
      development of AOD in patients with CML.

PMID- 28757618
TI  - Therapy-related myelodysplastic syndromes-specific risk stratification: are we
      putting the cart before the horse?

PMID- 28757620
TI  - Type 2 diabetes: Broccoli extract lowers glucose levels.

PMID- 28757621
TI  - Cardiovascular disease: CRHR2 blockade prevents heart failure.

PMID- 28757622
TI  - New cancer vaccines show clinical promise.

PMID- 28757623
TI  - FDA approves first new sickle cell drug in 20 years.

PMID- 28757619
TI  - Crystal structure of a Pseudomonas malonate decarboxylase holoenzyme hetero
      tetramer.
AB  - Pseudomonas species and other aerobic bacteria have a biotin-independent malonate
      decarboxylase that is crucial for their utilization of malonate as the sole
      carbon and energy source. The malonate decarboxylase holoenzyme contains four
      subunits, having an acyl-carrier protein (MdcC subunit) with a distinct
      prosthetic group, as well as decarboxylase (MdcD-MdcE) and acyl-carrier protein
      transferase (MdcA) catalytic activities. Here we report the crystal structure of
      a Pseudomonas malonate decarboxylase hetero-tetramer, as well as biochemical and
      functional studies based on the structural information. We observe a malonate
      molecule in the active site of MdcA and we also determine the structure of
      malonate decarboxylase with CoA in the active site of MdcD-MdcE. Both structures
      provide molecular insights into malonate decarboxylase catalysis. Mutations in
      the hetero-tetramer interface can abolish holoenzyme formation. Mutations in the
      hetero-tetramer interface and the active sites can abolish Pseudomonas aeruginosa
      growth in a defined medium with malonate as the sole carbon source.Some aerobic
      bacteria contain a biotin-independent malonate decarboxylase (MDC), which allows
      them to use malonate as the sole carbon source. Here, the authors present the
      crystal structure of a Pseudomonas MDC and give insights into its catalytic
      mechanism and function.

PMID- 28757624
TI  - Calls grow to tap the gold mine of human genetic knockouts.

PMID- 28757625
TI  - Joshua Gordon.

PMID- 28757626
TI  - Patent watch: Supreme Court decision favours biosimilars.

PMID- 28757627
TI  - Neurodegenerative disorders: SRC-ABL inhibitors protect motor neurons.

PMID- 28757628
TI  - FDA approvals for the first 6 months of 2017.

PMID- 28757629
TI  - Infectious diseases: Decrypting Cryptosporidium.

PMID- 28757630
TI  - Infectious diseases: Soil-sifting snags new antibiotic.

PMID- 28757632
TI  - Cancer: mRNA-encoded bispecific antibodies eliminate tumours.

PMID- 28757631
TI  - Cancer: RNA-based approaches target KRAS.

PMID- 28757634
TI  - Experimental concerns regarding suPAR-related proteinuria.

PMID- 28757636
TI  - SuPAR and FSGS: is the jury still out?

PMID- 28757637
TI  - Intravenous hydroxocobalamin and crystal nephropathy.

PMID- 28757638
TI  - Glomerular disease: Functional consequences of C5 nephritic factors in C3
      glomerulopathies.

PMID- 28757635
TI  - Mechanisms and consequences of carbamoylation.
AB  - Protein carbamoylation is a non-enzymatic post-translational modification that
      binds isocyanic acid, which can be derived from the dissociation of urea or from
      the myeloperoxidase-mediated catabolism of thiocyanate, to the free amino groups
      of a multitude of proteins. Although the term 'carbamoylation' is usually
      replaced by the term "carbamylation" in the literature, carbamylation refers to a
      different chemical reaction (the reversible interaction of CO2 with alpha and
      epsilon-amino groups of proteins). Depending on the altered molecule (for
      example, collagen, erythropoietin, haemoglobin, low-density lipoprotein or high
      density lipoprotein), carbamoylation can have different pathophysiological
      effects. Carbamoylated proteins have been linked to atherosclerosis, lipid
      metabolism, immune system dysfunction (such as inhibition of the classical
      complement pathway, inhibition of complement-dependent rituximab cytotoxicity,
      reduced oxidative neutrophil burst, and the formation of anti-carbamoylated
      protein antibodies) and renal fibrosis. In this Review, we discuss the
      carbamoylation process and evaluate the available biomarkers of carbamoylation
      (for example, homocitrulline, the percentage of carbamoylated albumin,
      carbamoylated haemoglobin, and carbamoylated low-density lipoprotein). We also
      discuss the relationship between carbamoylation and the occurrence of
      cardiovascular events and mortality in patients with chronic kidney disease and
      assess the effects of strategies to lower the carbamoylation load.

PMID- 28757639
TI  - Metabolic effects of resistance or high-intensity interval training among
      glycemic control-nonresponsive children with insulin resistance.
AB  - BACKGROUND: Little evidence exists on which variables of body composition or
      muscular strength mediates more glucose control improvements taking into account
      inter-individual metabolic variability to different modes of exercise training.
      OBJECTIVE: We examined 'mediators' to the effects of 6-weeks of resistance
      training (RT) or high-intensity interval training (HIT) on glucose control
      parameters in physically inactive schoolchildren with insulin resistance (IR).
      Second, we also determined both training-induce changes and the prevalence of
      responders (R) and non-responders (NR) to decrease the IR level. METHODS: Fifty
      six physically inactive children diagnosed with IR followed a RT or supervised
      HIT program for 6 weeks. Participants were classified based on DeltaHOMA-IR into
      glycemic control R (decrease in homeostasis model assessment-IR (HOMA-IR) <3.0
      after intervention) and NRs (no changes or values HOMA-IR?3.0 after
      intervention). The primary outcome was HOMA-IR associated with their mediators;
      second, the training-induced changes to glucose control parameters; and third the
      report of R and NR to improve body composition, cardiovascular, metabolic and
      performance variables. RESULTS: Mediation analysis revealed that improvements
      (decreases) in abdominal fat by the waist circumference can explain more the
      effects (decreases) of HOMA-IR in physically inactive schoolchildren under RT or
      HIT regimes. The same analysis showed that increased one-maximum repetition leg
      extension was correlated with the change in HOMA-IR (beta=-0.058; P=0.049).
      Furthermore, a change in the waist circumference fully mediated the dose-response
      relationship between changes in the leg-extension strength and HOMA-IR (beta'=
      0.004; P=0.178). RT or HIT were associated with significant improvements in body
      composition, muscular strength, blood pressure and cardiometabolic parameters
      irrespective of improvement in glycemic control response. Both glucose control RT
      R and HIT-R (respectively), had significant improvements in mean HOMA-IR, mean
      muscular strength leg-extension and mean measures of adiposity. CONCLUSIONS: The
      improvements in the lower body strength and the decreases in waist circumference
      can explain more the effects of the improvements in glucose control of IR
      schoolchildren in R group after 6 weeks of RT or HIT, showing both regimes
      similar effects on body composition or muscular strength independent of
      interindividual metabolic response variability.

PMID- 28757640
TI  - Effects of peripheral administration of a Neuromedin U receptor 2-selective
      agonist on food intake and body weight in obese mice.
AB  - BACKGROUND: Neuromedin U (NMU) is a neuropeptide with various physiological
      functions, including regulation of smooth-muscle contraction, blood pressure,
      stress responses and feeding behaviors. NMU activates two distinct receptors,
      NMUR1 and NMUR2, which are predominantly expressed in peripheral tissues and the
      central nervous system (CNS), respectively. It is reported that the NMU signaling
      system regulates food intake (FI) and body weight (BW) via NMUR2, suggesting that
      an NMUR2 agonist exhibiting anorectic effects would be a potential therapy for
      obesity. METHODS: Antiobesity effects of NMUR2 activation were assessed using a
      recently developed, novel NMUR2-selective agonist, NMU-7005 (a polyethylene
      glycolated octapeptide). Here we assessed cumulative FI and BW loss after
      peripheral administration of NMU-7005 in NMUR2 knockout and diet-induced obese
      mice. To gain mechanistic insights, we performed immunohistochemical analysis of
      c-Fos-like protein expression in the brain. RESULTS: We found that NMU-7005 was a
      NMUR2-selective agonist with little activity toward NMUR1. The anorectic effect
      of NMU-7005 was completely abrogated in NMUR2 knockout mice. Repeated
      subcutaneous administration of NMU-7005 showed a potent antiobesity effect with
      FI inhibition (P<0.025) in diet-induced obese mice. NMU-7005 in combination with
      the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide showed an
      additive antiobesity effect, suggesting that NMUR2-mediated anorectic action is
      different from that of GLP-1R agonists. NMU-7005 also elicited a minimal
      conditioned taste-aversive effect, while the effect of liraglutide was
      significant. As c-Fos expression was upregulated in the hypothalamus and the
      medulla oblongata in NMU-7005-administered mice, the pharmacological effects of
      NMU-7005 appeared to be mediated via activation of the CNS. CONCLUSION: Our
      results demonstrated that a novel NMUR2-selective agonist, NMU-7005, is a
      beneficial tool for the elucidation of NMUR2-mediated physiological functions,
      which is a promising therapeutic strategy for treating obesity.

PMID- 28757644
TI  - Bacterial physiology: Raising the alarm.

PMID- 28757642
TI  - Mexican-origin male perspectives of diet-related behaviors associated with weight
      management.
AB  - BACKGROUND: Prevalence rates of obesity and related diseases are quickly reaching
      epidemic proportions among Hispanic males in the United States. Hispanic males
      suffer from the highest prevalence of obesity-related diseases when compared to
      all other racial/ethnic groups. Despite evidence showing that weight loss can
      significantly reduce the risk of obesity-related health implications, literature
      informing best practices to engage Hispanic males in weight management programs
      is scarce. PURPOSE: The purpose of the current study was to engage Spanish
      speaking, Mexican-origin males with overweight or obesity to examine their
      perspectives of diet-related behaviors related to weight management. METHODS:
      Demographic and acculturation data were collected using questionnaires. Fourteen
      semistructured interviews were completed with an all-Spanish-speaking cohort of
      men (age: 45.0+/-9.8 years; BMI: 34.2+/-6.5 kg m-2) who were born outside of the
      United States. We conducted a thematic analysis using a hybrid deductive
      inductive analysis strategy using a previously developed codebook that was
      updated during iterative analysis of interview transcripts. RESULTS: Participants
      reported that healthful eating habits were hindered, among other factors, by lack
      of knowledge, sociocultural norms and conceptualizations of masculinity. Viable
      diet-related intervention approaches also surfaced, including building
      consciousness, promotion of traditional knowledge and the integration of the
      family in interventions. CONCLUSION: Findings suggest that Spanish-speaking,
      Mexican-origin men have interest in actively engaging in behavior changes that
      improve their dietary habits and engage in weight management. Our findings yield
      valuable insights that can be used to formulate tailored intervention strategies
      to improve obesity prevention and treatment programs for this vulnerable
      subgroup.

PMID- 28757641
TI  - Education as a moderator of genetic risk for higher body mass index: prospective
      cohort study from childhood to adulthood.
AB  - OBJECTIVES: The life-course development of body mass index (BMI) may be driven by
      interactions between genes and obesity-inducing social environments. We examined
      whether lower parental or own education accentuates the genetic risk for higher
      BMI over the life course, and whether diet and physical activity account for the
      educational differences in genetic associations with BMI. SUBJECTS/METHODS: The
      study comprised 2441 participants (1319 women, 3-18 years at baseline) from the
      prospective, population-based Cardiovascular Risk in Young Finns Study. BMI
      (kg/m2) trajectories were calculated from 18 to 49 years, using data from six
      time points spanning 31 years. A polygenic risk score for BMI was calculated as a
      weighted sum of risk alleles in 97 single-nucleotide polymorphisms. Education was
      assessed via self-reports, measured prospectively from participants in adulthood
      and from parents when participants were children. Diet and physical activity were
      self-reported in adulthood. RESULTS: Mean BMI increased from 22.6 to 26.6 kg/m2
      during the follow-up. In growth curve analyses, the genetic risk score was
      associated with faster BMI increase over time (b=0.02, (95% CI, 0.01-0.02,
      P<0.001)). The association between the genetic risk score and BMI was more
      pronounced among those with lower educational level in adulthood (b=-0.12 (95%
      CI, -0.23-0.01); P=0.036)). No interaction effect was observed between the
      genetic risk score and parental education (b=0.05 (95% CI, -0.09-0.18; P=0.51)).
      Diet and physical activity explained little of the interaction effect between the
      genetic risk score and adulthood education. CONCLUSIONS: In this prospective
      study, the association of a risk score of 97 genetic variants with BMI was
      stronger among those with low compared with high education. This suggests lower
      education in adulthood accentuates the risk of higher BMI in people at genetic
      risk.

PMID- 28757643
TI  - Birth by cesarean section in relation to adult offspring overweight and
      biomarkers of cardiometabolic risk.
AB  - BACKGROUND: Birth by Cesarean section (C-section) may increase the risk for non
      communicable diseases. We aimed to examine the relation of birth by C-section
      with offspring overweight and markers of cardiometabolic risk in a prospective
      observational cohort with 20 years of follow-up. METHODS: The Danish Fetal
      Origins Cohort enrolled 965 pregnant women in 1988-1989. In 2008, a follow-up
      study of the offspring was completed. The offspring were invited to participate
      in a clinical examination with measurements of anthropometry and a fasting blood
      sample (n=443). In addition, 252 offspring completed a self-administered
      questionnaire with questions on height and weight, leaving us with a study sample
      of 695 offspring. Offspring overweight at 20 years was defined as body mass index
      (BMI)?25 kg m-2. We also analyzed blood pressure and fasting blood samples for
      cardiometabolic risk factors including insulin, leptin and adiponectin, and lipid
      concentrations. RESULTS: In the cohort, 7% were born by C-section, and at age 20
      years, 18% of the offspring had a BMI ?25 kg m-2. Birth by C-section was
      associated with increased odds of overweight or obesity at 20 years (Odds
      ratio=2.17 (95% confidence interval (CI): 1.10, 4.27)) after adjustment for
      potential confounders. Birth by C-section was also associated with higher serum
      concentrations of total cholesterol (8.5%, 95% CI: 1.1-16.5), low-density
      lipoprotein cholesterol (12.6%, 95% CI: 1.0, 25.5), leptin (73.1%, 95% CI: 5.9,
      183.1) and Apolipoprotein B (0.08 g l-1, 95% CI: 0.04, 0.15). In contrast, birth
      by C-section was not related to blood pressure or serum concentrations of
      insulin, adiponectin, triglycerides, high-density lipoprotein or Apolipoprotein
      A. CONCLUSION: Birth by C-section was associated with higher frequency of
      dysmetabolic traits in offspring independently of shared risk factors. Further
      research aimed at replicating these findings and elucidating the underlying
      biological mechanisms of this relation is needed.

PMID- 28757645
TI  - Viral pathogenesis: Finding the enemy within.

PMID- 28757646
TI  - Biofilms: Building up the matrix.

PMID- 28757647
TI  - Parasite genomics: Screening for the essentials.

PMID- 28757649
TI  - Greater Engagement Among Members of Gay-Straight Alliances: Individual and
      Structural Contributors.
AB  - Using youth program models to frame the study of Gay-Straight Alliances (GSAs),
      we identified individual and structural predictors of greater engagement in these
      settings with a cross-sectional sample of 295 youth in 33 GSAs from the 2014
      Massachusetts GSA Network Survey (69% LGBQ, 68% cisgen-der female, 68% White,
      Mage = 16.07). Multilevel modeling results indicated that members who perceived
      more support/socializing from their GSA, had more LGB friends, were longer
      serving members, and were in GSAs with more open and respectful climates reported
      greater engagement. Further, there was a curvilinear association between
      organizational structure in the GSA and engagement: Perceptions of more structure
      were associated with greater engagement to a point, after which greater structure
      was related to less engagement.

PMID- 28757650
TI  - Data integration with high dimensionality.
AB  - We consider situations where the data consist of a number of responses for each
      individual, which may include a mix of discrete and continuous variables. The
      data also include a class of predictors, where the same predictor may have
      different physical measurements across different experiments depending on how the
      predictor is measured. The goal is to select which predictors affect any of the
      responses, where the number of such informative predictors tends to infinity as
      the sample size increases. There are marginal likelihoods for each experiment; we
      specify a pseudolikelihood combining the marginal likelihoods, and propose a
      pseudolikelihood information criterion. Under regularity conditions, we establish
      selection consistency for this criterion with unbounded true model size. The
      proposed method includes a Bayesian information criterion with appropriate
      penalty term as a special case. Simulations indicate that data integration can
      dramatically improve upon using only one data source.

PMID- 28757648
TI  - Prediction of antibiotic resistance: time for a new preclinical paradigm?
AB  - Predicting the future is difficult, especially for evolutionary processes that
      are influenced by numerous unknown factors. Still, this is what is required of
      drug developers when they assess the risk of resistance arising against a new
      antibiotic candidate during preclinical development. In this Opinion article, we
      argue that the traditional procedures that are used for the prediction of
      antibiotic resistance today could be markedly improved by including a broader
      analysis of bacterial fitness, infection dynamics, horizontal gene transfer and
      other factors. This will lead to more informed preclinical decisions for
      continuing or discontinuing the development of drug candidates.

PMID- 28757651
TI  - Sampling random directions within an elliptical cone.
AB  - This work extends the spherical surface sampling algorithm in order to uniformly
      generate random directions within an elliptical cone. This has applications in
      Monte Carlo particle transport simulations, for example modeling asymmetric beam
      divergence or scattering interactions. Two methods are presented. The first obeys
      the strict boundary of the elliptical cone. The second relaxes this requirement,
      increasing the range of generated directions by up to 10% for elliptical cones of
      extreme eccentricity. However, the second method is able to generate directions
      beyond the equator.

PMID- 28757652
TI  - Genetic Breast Cancer Susceptibility Variants and Prognosis in the Prospectively
      Randomized SUCCESS A Study.
AB  - Large-scale genotyping studies have identified over 70 single nucleotide
      polymorphisms (SNPs) associated with breast cancer (BC) risk. However, knowledge
      regarding genetic risk factors associated with the prognosis is limited. The aim
      of this study was therefore to investigate the prognostic effect of nine known
      breast cancer risk SNPs. BC patients (n = 1687) randomly sampled in an adjuvant,
      randomized phase III trial (SUCCESS A study) were genotyped for nine BC risk
      SNPs: rs17468277 (CASP8) , rs2981582 (FGFR2) , rs13281615(8q24), rs3817198 (LSP1)
      , rs889312 (MAP3K1) , rs3803662 (TOX3) , rs13387042(2q35), rs4973768 (SLC4A7) ,
      rs6504950 (COX11) . Cox proportional hazards models were used to test the SNPs'
      association with overall survival (OS) and progression-free survival (PFS).
      Additional analyses were carried out for molecular subgroups. rs3817198 in LSP1
      (lymphocyte-specific protein 1) was the only SNP that significantly influenced OS
      (p = 0.01) and PFS (p < 0.01) in the likelihood ratio test comparing the genetic
      survival model with the clinical survival model. In the molecular subgroups,
      triple-negative patients with two minor alleles in rs3817198 had a much better
      prognosis relative to OS (adjusted HR 0.03; 95% CI 0.002 - 0.279) and PFS (HR
      0.09; 95% CI 0.02 - 0.36) than patients with the common alleles. The same effect
      on PFS was shown for patients with luminal A tumors (HR 0.19; 95% CI 0.05 -
      0.84), whereas patients with luminal B tumors had a poorer PFS with two minor
      alleles (HR 2.13; 95% CI 1.02 - 4.40). The variant in rs3817198 has a prognostic
      effect particularly in the subgroup of patients with triple-negative BC,
      suggesting a possible link with immunomodulation and BC.

PMID- 28757653
TI  - Distinct Pattern of Metastases in Patients with Invasive Lobular Carcinoma of the
      Breast.
AB  - BACKGROUND: Invasive lobular carcinoma (ILC) comprises around 10 - 15% of
      invasive breast cancers. Few prior studies have demonstrated a unique pattern of
      metastases between ILC and the more common invasive ductal carcinoma (IDC). To
      our knowledge, such data is limited to first sites of distant recurrence. We
      aimed to perform a comparison of the metastatic pattern of ILC and IDC at first
      distant recurrence as well as over the entire course of metastatic disease.
      METHODS: We used a prospectively collated database of patients with metastatic
      breast cancer. Breast cancer recurrence or metastases were classified into
      various sites and a descriptive analysis was performed. RESULTS: Among 761
      patients, 88 (11.6%) were diagnosed with ILC and 673 (88.4%) with IDC. Patients
      with ILC showed more frequent metastases to the bone (56.8 vs. 37.7%, p = 0.001)
      and gastrointestinal (GI) tract (5.7 vs. 0.3%, p < 0.001) as first site of
      distant recurrence, and less to organs such as lung (5.7 vs. 24.2%, p < 0.001)
      and liver (4.6 vs. 11.4%, p = 0.049). Over the entire course of metastatic
      disease, more patients with ILC had ovarian (5.7 vs. 2.1%, p = 0.042) and GI
      tract metastases (8.0 vs. 0.6%, p < 0.001), also demonstrating reduced tendency
      to metastasize to the liver (20.5 vs. 49.0%, p < 0.001) and lung (23.9 vs. 51.9%,
      p < 0.001). All associations but bone held after sensitivity analysis on hormonal
      status. Although patients presenting with ILC were noted to have more advanced
      stage at presentation, recurrence-free survival in these patients was increased
      (4.8 years vs. 3.2 years, p = 0.017). However, overall survival was not (2.5 vs.
      2.0 years, p = 0.75). CONCLUSION: After accounting for hormone receptor status,
      patients with IDC had greater lung/pleura and liver involvement, while patients
      with ILC had a greater propensity to develop ovarian and GI metastases both at
      first site and overall. Clinicians can use this information to provide more
      directed screening for metastases; it also adds to the argument that these two
      variants of breast cancer should be managed as unique diseases.

PMID- 28757655
TI  - Traditional Gymnastic Exercises for the Pelvic Floor Often Lead to Bladder Neck
      Descent - a Study Using Perineal Ultrasound.
AB  - BACKGROUND: The aims of physiotherapy in stress incontinent women are to improve
      pelvic floor function and the continence mechanism including bladder neck support
      and urethral closure pressure. In Germany, traditional conservative treatment
      often includes gymnastic exercises with unclear effects on the bladder neck. The
      aim of this study was to sonographically assess bladder neck movements during
      selected exercises. METHODS: Fifteen healthy, continent women without previous
      vaginal births, who were able to voluntarily contract their pelvic floor muscels
      performed the shoulder bridge, the abdominal press, tiptoe and the Pilates clam
      exercises. The first set was performed without any additional instructions.
      During the second set directions were given to activate the pelvic floor before
      beginning each exercise and to maintain the contraction throughout the exercise.
      Bladder neck movement was measured on perineal ultrasound using a validated
      method with the pubic symphysis as a reference point. RESULTS: The median age of
      participants was 32 years, median BMI was 23. Eight women were nulliparous and
      seven had given birth to 1 - 2 children via caesarean section. When exercises
      were performed without voluntary pelvic floor contraction the bladder neck
      descended on average between 2.3 and 4.4 mm, and with pelvic floor contraction
      prior to the exercise only between 0.5 and 2.1 mm (p > 0.05 except for abdominal
      press p = 0.007). The Pilates clam exercise and toe stand stabilised the bladder
      neck most effectively. DISCUSSION: Bladder neck descent often occurs during
      pelvic floor gymnastic exercises as traditionally performed in Germany, and a
      voluntary pelvic floor contraction during the exercises does not necessarily
      prevent this.

PMID- 28757654
TI  - Predicting Triple-Negative Breast Cancer Subtype Using Multiple Single Nucleotide
      Polymorphisms for Breast Cancer Risk and Several Variable Selection Methods.
AB  - INTRODUCTION: Studies of triple-negative breast cancer have recently been
      extending the inclusion criteria and incorporating additional molecular markers
      into the selection criteria, opening up scope for targeted therapies. The
      screening phases required for studies of this type are often prolonged, since the
      process of determining the molecular subtype and carrying out additional
      biomarker assessment is time-consuming. Parameters such as germline genotypes
      capable of predicting the molecular subtype before it becomes available from
      pathology might be helpful for treatment planning and optimizing the timing and
      cost of screening phases. This appears to be feasible, as rapid and low-cost
      genotyping methods are becoming increasingly available. The aim of this study was
      to identify single nucleotide polymorphisms (SNPs) for breast cancer risk capable
      of predicting triple negativity, in addition to clinical predictors, in breast
      cancer patients. METHODS: This cross-sectional observational study included 1271
      women with invasive breast cancer who were treated at a university hospital. A
      total of 76 validated breast cancer risk SNPs were successfully genotyped.
      Univariate associations between each SNP and triple negativity were explored
      using logistic regression analyses. Several variable selection and regression
      techniques were applied to identify a set of SNPs that together improve the
      prediction of triple negativity in addition to the clinical predictors of age at
      diagnosis and body mass index (BMI). The most accurate prediction method was
      determined by cross-validation. RESULTS: The SNP rs10069690 (TERT, CLPTM1L) was
      the only significant SNP (corrected p = 0.02) after correction of p values for
      multiple testing in the univariate analyses. This SNP and three additional SNPs
      from the genes RAD51B, CCND1, and FGFR2 were selected for prediction of triple
      negativity. The addition of these SNPs to clinical predictors increased the cross
      validated area under the curve (AUC) from 0.618 to 0.625. Age at diagnosis was
      the strongest predictor, stronger than any genetic characteristics. CONCLUSION:
      Prediction of triple-negative breast cancer can be improved if SNPs associated
      with breast cancer risk are added to a prediction rule based on age at diagnosis
      and BMI. This finding could be used for prescreening purposes in complex
      molecular therapy studies for triple-negative breast cancer.

PMID- 28757656
TI  - Can the Rate of C-sections Performed in a Level I Perinatal Center Be Reduced? -
      An Analysis of the University Gynecology Clinic Rostock, 2008 - 2014.
AB  - INTRODUCTION: In Germany the rate of deliveries by cesarean section is
      continually increasing. Many different reasons have been put forward to explain
      this trend. The aim of this study was to examine how the C-section rate developed
      at the University Gynecology Clinic Rostock, one of the biggest maternity
      hospitals and level I perinatal centers in Germany, based on various maternal and
      neonatal parameters. The aim was also to identify potential risk factors for C
      sections. MATERIAL AND METHOD: Various obstetric parameters were obtained from
      the birth cohort (2008 to 2014; n = 20 091) of the University Gynecology Clinic
      Rostock. The data was used to calculate parameter-specific C-section rates.
      Potential risk factors for C-section were identified by regression analysis.
      RESULTS: The C-section rate dropped from 26.24% to 23.57%. The rate of repeat C
      sections also declined. The mean age of the pregnant women increased.
      Nevertheless, the frequency of cesarean sections in pregnant women aged more than
      35 years declined. Rates of being overweight or obese preconception increased. C
      section rates increased as BMI values preconception increased. There was a
      perceptible trend towards attempting the vaginal delivery of children in breech
      presentation and of twins. The frequency of depressed neonates after vaginal
      delivery and after C-section decreased. Rates for mild and advanced acidosis
      increased after both C-sections and vaginal deliveries. Previous C-section, older
      maternal age, overweight and obesity prior to conception, breech presentation and
      multiple pregnancies all increased the risk of cesarean sections. CONCLUSION:
      This study showed that reducing the rates of C-sections without a deterioration
      in neonatal outcomes can be achieved even in a large maternity hospital that
      cares for many high-risk pregnancies.

PMID- 28757658
TI  - Convergent structure and function of mycelial galleries in two unrelated
      Neotropical plant-ants.
AB  - The construction process and use of galleries by Azteca brevis (Myrmicinae:
      Dolichoderinae) inhabiting Tetrathylacium macrophyllum (Salicaceae) were compared
      with Allomerus decemarticulatus (Myrmicinae: Solenopsidini) galleries on Hirtella
      physophora (Chrysobalanaceae). Though the two ant species are phylogenetically
      distant, the gallery structure seems to be surprisingly similar and structurally
      convergent: both are pierced with numerous holes and both ant species use
      Chaetothyrialean fungi to strengthen the gallery walls. Al. decemarticulatus is
      known to use the galleries for prey capture and whether this is also the case for
      Az. brevis was tested in field experiments. We placed Atta workers as potential
      prey/threat on the galleries and recorded the behaviour of both ant species. We
      found considerable behavioural differences between them: Al. decemarticulatus was
      quicker and more efficient at capture than was Az. brevis. While most Atta
      workers were captured after the first 5 min by Al. decemarticulatus,
      significantly fewer were captured by Az. brevis even after 20 min. Moreover, the
      captured Atta were sometimes simply discarded and not taken to the nest by Az.
      brevis. As a consequence, the major function of the galleries built by Az. brevis
      may, therefore, be defense against intruders in contrast to Al. decemarticulatus
      which uses them mainly for prey capture. This may be due to a higher need for
      protein in Al. decemarticulatus compared to coccid-raising Az. brevis.

PMID- 28757659
TI  - Prediction of entropy stabilized incommensurate phases in the system MoS2 -MoTe2.
AB  - A first principles phase diagram calculation, that included van der Waals
      interactions, was performed for the 3D bulk system (1 - X) . MoS2 - (X) . MoTe2.
      Surprisingly, the predicted phase diagram has at least two ordered phases, at X ~
      0:46, even though all calculated formation energies are positive; in a ground
      state analysis that examined all configurations with 16 or fewer anion sites. The
      lower-temperature I-phase is predicted to transform to a higher-temperature I'
      phase at T ~ 500 K, and I' disorders at T ~ 730 K. Both these transitions are
      predicted to be first-order, and there are broad two-phase fields on both sides
      of the ordered regions. Both the I- and I'-phases are predicted to be
      incommensurate, i.e., aperiodic: I-phase in three dimensions; and I'-phase in two
      dimensions.

PMID- 28757660
TI  - A Demographic Deficit? Local Population Aging and Access to Services in Rural
      America, 1990-2010.
AB  - Population aging is being experienced by many rural communities in the U.S., as
      evidenced by increases in the median age and the high incidence of natural
      population decrease. The implications of these changes in population structure
      for the daily lives of the residents in such communities have received little
      attention. We address this issue in the current study by examining the
      relationship between population aging and the availability of service-providing
      establishments in the rural U.S. between 1990 and 2010. Using data mainly from
      the U.S. Census Bureau and the Bureau of Labor Statistics, we estimate a series
      of fixed-effects regression models to identify the relationship between median
      age and establishment counts net of changes in overall population and other
      factors. We find a significant, but non-linear relationship between county median
      age and the total number of service-providing establishments, and counts of most
      specific types of services. We find a positive effect of total population size
      across all of our models. This total population effect is consistent with other
      research, but the independent effects of age structure that we observe represent
      a novel finding and suggest that age structure is a salient factor in local rural
      development and community wellbeing.

PMID- 28757657
TI  - Advances in two photon scanning and scanless microscopy technologies for
      functional neural circuit imaging.
AB  - Recent years have seen substantial developments in technology for imaging neural
      circuits, raising the prospect of large scale imaging studies of neural
      populations involved in information processing, with the potential to lead to
      step changes in our understanding of brain function and dysfunction. In this
      article we will review some key recent advances: improved fluorophores for single
      cell resolution functional neuroimaging using a two photon microscope; improved
      approaches to the problem of scanning active circuits; and the prospect of
      scanless microscopes which overcome some of the bandwidth limitations of current
      imaging techniques. These advances in technology for experimental neuroscience
      have in themselves led to technical challenges, such as the need for the
      development of novel signal processing and data analysis tools in order to make
      the most of the new experimental tools. We review recent work in some active
      topics, such as region of interest segmentation algorithms capable of demixing
      overlapping signals, and new highly accurate algorithms for calcium transient
      detection. These advances motivate the development of new data analysis tools
      capable of dealing with spatial or spatiotemporal patterns of neural activity,
      that scale well with pattern size.

PMID- 28757661
TI  - Mineral and Anthropogenic Indicator Inorganics in Urban Stormwater and Snowmelt
      Runoff: Sources and Mobility Patterns.
AB  - Inorganic chemicals in urban stormwater and snowmelt runoff originate from
      catchment geology and anthropogenic activities. The occurrence, partitioning and
      mobility of six minerals and six trace metal (TM) indicators of anthropogenic
      activities were studied in stormwater, snowmelt and baseflow in four urban
      catchments, and the sampling of inorganics was supplemented by measurements of
      electrical conductivity (EC), pH and total suspended solids (TSSs). Minerals
      occurred at concentrations several orders of magnitude higher (1-102 mg/L) than
      those of TMs (10-2-102 MUg/L) and reflected the composition of local groundwater
      seeping into sewers. Concentrations of Ca, K, Mg and Na were enhanced by baseflow
      contributions and followed closely the electrical conductivity. Al and Fe
      minerals occurred in insoluble forms, and their pollutographs were similar to
      those of TMs, whose concentrations mimicked, to some extent, the flux of TSS. The
      TMs with the highest and lowest particulate fractions were Cr&Pb and Cu&Zn,
      respectively. The concentrations of total TMs in snowmelt were two to four times
      higher than those in stormwater, and both sources likely exceeded some of the
      stormwater effluent limits (for Cd, Cu and Zn) proposed in Sweden. Where such
      concentrations depended on water hardness, the risk of toxicity might be reduced
      by elevated hardness of the monitored snowmelt and stormwater. Recognizing the
      good ecological status of the study area receiving water, Lake Storsjon, some
      protection against polluted runoff and snowmelt may be needed and could be
      achieved by implementing stormwater management measures controlling TSS and TMs.

PMID- 28757662
TI  - Selective Separation of Chromium Species from Soils by Single-Step Extraction
      Methods: a Critical Appraisal.
AB  - A critical appraisal of single-step extraction procedures of chromium species
      from soil was done in terms of their selectivity towards Cr(III) and Cr(VI)
      species. Samples of natural mineral and organic soil and samples of soil enriched
      with different chromium compounds of various solubility (in liquid or solid form)
      were used to simulate contamination of soil by liquid and solid wastes. The
      efficiency of extraction of Cr(III) and Cr(VI) species with various reagents,
      e.g. acetic acid, chelating agents (EDTA, DTPA) or inorganic salts (phosphates
      and carbonates), was evaluated on the basis of recovery results obtained for
      enriched samples. None of used reagents allow for quantitative extraction of
      added Cr(III) form. Procedures based on extraction of soil with Na2CO3 at room
      and elevated temperature (90-95  degrees C) were suitable for extraction of
      Cr(VI) species from mineral soil, whereas for organic soil, the procedure based
      on extraction with Na2CO3 at room temperature was recommended. The developed
      extraction procedures were validated using certified reference material (CRM 041
      soil) and applied for analysis of contaminated soil samples. The studies showed
      that the physical state of waste, initial form and oxidation state of chromium
      and soil properties influenced the final chromium species and their mobility in
      soil, which have an impact on contamination of environment. The analysis of
      contaminated soil samples from a tannery area showed that the share of Cr(VI) was
      very low (only 0.8-4.5%) despite the high total content of chromium, which
      confirmed that chromium was present in immobile forms.

PMID- 28757663
TI  - Social Support Influences on Substance Abuse Outcomes Among Sober Living House
      Residents with Low and Moderate Psychiatric Severity.
AB  - Social support and psychiatric severity are known to influence substance abuse.
      However, little is known about how their influences vary under different
      conditions. We aimed to study how different types of social support were
      associated with substance abuse outcomes among persons with low and moderate
      psychiatric severity who entered Sober Living Houses (SLHs). Two hundred forty
      five individuals entering 16 SLHs were interviewed at baseline and 6, 12, and 18
      months. The Brief Symptom Inventory assessed psychiatric symptoms and the
      Important People Instrument and a modified AA Affiliation Scale assessed social
      support. Social support variables predicted substance abuse outcomes for persons
      with low and moderate psychiatric severity. However, they were the strongest and
      most consistent predictors for the low severity group.

PMID- 28757664
TI  - MIMICKING COUNTERFACTUAL OUTCOMES TO ESTIMATE CAUSAL EFFECTS.
AB  - In observational studies, treatment may be adapted to covariates at several times
      without a fixed protocol, in continuous time. Treatment influences covariates,
      which influence treatment, which influences covariates, and so on. Then even time
      dependent Cox-models cannot be used to estimate the net treatment effect.
      Structural nested models have been applied in this setting. Structural nested
      models are based on counterfactuals: the outcome a person would have had had
      treatment been withheld after a certain time. Previous work on continuous-time
      structural nested models assumes that counterfactuals depend deterministically on
      observed data, while conjecturing that this assumption can be relaxed. This
      article proves that one can mimic counterfactuals by constructing random
      variables, solutions to a differential equation, that have the same distribution
      as the counterfactuals, even given past observed data. These "mimicking"
      variables can be used to estimate the parameters of structural nested models
      without assuming the treatment effect to be deterministic.

PMID- 28757665
TI  - Passive Microlesion Detection and Mapping for Treatment of Hypertrophic
      Cardiomyopathy.
AB  - Intermittent high intensity ultrasound pulses with circulating contrast agent
      microbubbles can induce scattered microlesions of potential value for myocardial
      reduction therapy. This paper presents an in vitro setup imitating the treatment
      for monitoring development. A preclinical imaging system with a single element
      transducer, synchronization and receive-only imaging transducer array has been
      implemented on a research platform. Contrast agent microbubbles pumped in a
      dialysis tubing setup were exposed to high intensity focused ultrasound at
      1.0/3.5 MHz center frequencies. Polystyrene spheres were employed as linear
      scatterers compared to contrast agents for system transfer function equalization.
      A cavitation mapping technique was employed to spatially locate and depict
      microbubble activity during treatment. For high acoustic pressure amplitudes a 5
      dB difference between contrast agent and solid spheres was observed and spatially
      mapped. The in-plane resolution was 4.5 mm for axial and 1.5 mm laterally. In the
      future, this cavitation detection scheme will be applied to monitor in vivo
      microlesioning in real-time.

PMID- 28757666
TI  - Generating an image that affords slant perception from stereo, without pictorial
      cues.
AB  - This paper describes an algorithm for generating a planar image that when tilted
      provides stereo cues to slant, without contamination from pictorial gradients. As
      the stimuli derived from this image are ultimately intended for use in studies of
      slant perception under magnification, a further requirement is that the generated
      image be suitable for high-definition printing or display on a monitor. A first
      stage generates an image consisting of overlapping edges with sufficient density
      that when zoomed, edges that nearly span the original scale are replaced with
      newly emergent content that leaves the visible edge statistics unchanged. A
      second stage reduces intensity clumping while preserving edges by enforcing a
      broad dynamic range across the image. Spectral analyses demonstrate that the low
      frequency content of the resulting image, which would correspond to the pictorial
      cue of texture gradient changes under slant, (a) has a power fall-off deviating
      from 1/f noise (to which the visual system is particularly sensitive), and (b)
      does not offer systematic cues under changes in scale or slant. Two behavioral
      experiments tested whether the algorithm generates stimuli that offer cues to
      slant under stereo viewing only, and not when disparities are eliminated. With a
      particular adjustment of dynamic range (and nearly so with the other version that
      was tested), participants viewing without stereo cues were essentially unable to
      discriminate slanted from flat (frontal) stimuli, and when slant was reported,
      they failed to discriminate its direction. In contrast, non-stereo viewing of a
      control stimulus with pictorial cues, as well as stereoscopic observation,
      consistently allowed participants to perceive slant correctly. Experiment 2
      further showed that these results generalized across a population of different
      stimuli from the same generation process and demonstrated that the process did
      not substitute biased slant cues.

PMID- 28757667
TI  - When sex doesn't sell to men: mortality salience, disgust and the appeal of
      products and advertisements featuring sexualized women.
AB  - Although men typically hold favorable views of advertisements featuring female
      sexuality, from a Terror Management Theory perspective, this should be less the
      case when thoughts of human mortality are salient. Two experiments conducted in
      South Korea supported this hypothesis across a variety of products (e.g., perfume
      and vodka). Men became more negative towards advertisements featuring female
      sexuality, and had reduced purchase intentions for those products, after thinking
      about their own mortality. Study 2 found that these effects were mediated by
      heightened disgust. Mortality thoughts did not impact women in either study.
      These findings uniquely demonstrate that thoughts of death interact with female
      sex-appeal to influence men's consumer choices, and that disgust mediates these
      processes. Implications for the role of emotion, and cultural differences, in
      terror management, for attitudes toward female sexuality, and for marketing
      strategies are discussed.

PMID- 28757668
TI  - Perceiving emotion in non-social targets: The effect of trait empathy on
      emotional contagion through art.
AB  - This research examines the role of trait empathy in emotional contagion through
      non-social targets-art objects. Studies 1a and 1b showed that high- (compared to
      low-) empathy individuals are more likely to infer an artist's emotions based on
      the emotional valence of the artwork and, as a result, are more likely to
      experience the respective emotions themselves. Studies 2a and 2b experimentally
      manipulated artists' emotions via revealing details about their personal life.
      Study 3 experimentally induced positive vs. negative emotions in individuals who
      then wrote literary texts. These texts were shown to another sample of
      participants. High- (compared to low-) empathy participants were more like to
      accurately identify and take on the emotions ostensibly (Studies 2a and 2b) or
      actually (Study 3) experienced by the "artists". High-empathy individuals'
      enhanced sensitivity to others' emotions is not restricted to social targets,
      such as faces, but extends to products of the human mind, such as objects of art.

PMID- 28757669
TI  - Comment.
AB  - This comment deals with issues related to the article by Chen, Zeng, and Kosorok.
      We present several potential modifications of the outcome weighted learning
      approach. Those modifications are based on truncated l2 loss. One advantage of l2
      loss is that it is differentiable everywhere, which makes it more stable and
      computationally more tractable.

PMID- 28757670
TI  - Energy Efficiency Challenges of 5G Small Cell Networks.
AB  - The deployment of a large number of small cells poses new challenges to energy
      efficiency, which has often been ignored in fifth generation (5G) cellular
      networks. While massive multiple-input multiple outputs (MIMO) will reduce the
      transmission power at the expense of higher computational cost, the question
      remains as to which computation or transmission power is more important in the
      energy efficiency of 5G small cell networks. Thus, the main objective in this
      paper is to investigate the computation power based on the Landauer principle.
      Simulation results reveal that more than 50% of the energy is consumed by the
      computation power at 5G small cell base stations (BSs). Moreover, the computation
      power of 5G small cell BS can approach 800 watt when the massive MIMO (e.g., 128
      antennas) is deployed to transmit high volume traffic. This clearly indicates
      that computation power optimization can play a major role in the energy
      efficiency of small cell networks.

PMID- 28757671
TI  - Slowed articulation rate is a sensitive diagnostic marker for identifying non
      fluent primary progressive aphasia.
AB  - BACKGROUND: Primary progressive aphasia (PPA) is a neurodegenerative aphasic
      syndrome with three distinct clinical variants: non-fluent (nfvPPA), logopenic
      (lvPPA), and semantic (svPPA). Speech (non-) fluency is a key diagnostic marker
      used to aid identification of the clinical variants, and researchers have been
      actively developing diagnostic tools to assess speech fluency. Current approaches
      reveal coarse differences in fluency between subgroups, but often fail to clearly
      differentiate nfvPPA from the variably fluent lvPPA. More robust subtype
      differentiation may be possible with finer-grained measures of fluency. AIMS: We
      sought to identify the quantitative measures of speech rate-including
      articulation rate and pausing measures-that best differentiated PPA subtypes,
      specifically the non-fluent group (nfvPPA) from the more fluent groups (lvPPA,
      svPPA). The diagnostic accuracy of the quantitative speech rate variables was
      compared to that of a speech fluency impairment rating made by clinicians.
      METHODS AND PROCEDURES: Automatic estimates of pause and speech segment durations
      and rate measures were derived from connected speech samples of participants with
      PPA (N=38; 11 nfvPPA, 14 lvPPA, 13 svPPA) and healthy age-matched controls (N=8).
      Clinician ratings of fluency impairment were made using a previously validated
      clinician rating scale developed specifically for use in PPA. Receiver operating
      characteristic (ROC) analyses enabled a quantification of diagnostic accuracy.
      OUTCOMES AND RESULTS: Among the quantitative measures, articulation rate was the
      most effective for differentiating between nfvPPA and the more fluent lvPPA and
      svPPA groups. The diagnostic accuracy of both speech and articulation rate
      measures was markedly better than that of the clinician rating scale, and
      articulation rate was the best classifier overall. Area under the curve (AUC)
      values for articulation rate were good to excellent for identifying nfvPPA from
      both svPPA (AUC=.96) and lvPPA (AUC=.86). Cross-validation of accuracy results
      for articulation rate showed good generalizability outside the training dataset.
      CONCLUSIONS: Results provide empirical support for (1) the efficacy of
      quantitative assessments of speech fluency and (2) a distinct non-fluent PPA
      subtype characterized, at least in part, by an underlying disturbance in speech
      motor control. The trend toward improved classifier performance for quantitative
      rate measures demonstrates the potential for a more accurate and reliable
      approach to subtyping in the fluency domain, and suggests that articulation rate
      may be a useful input variable as part of a multi-dimensional clinical subtyping
      approach.

PMID- 28757672
TI  - Aggressive behaviours track transitions in seasonal phenotypes of female Siberian
      hamsters.
AB  - Seasonally breeding animals exhibit profound physiological and behavioural
      responses to changes in ambient day length (photoperiod), including changes in
      reproductive function and territorial aggression.Species where aggression
      persists when gonads are regressed and circulating levels of gonadal hormones are
      low, such as Siberian hamsters (Phodopus sungorus) and song sparrows (Melospiza
      melodia), challenge the well-established framework that gonadal hormones are
      important mediators of aggression.A solution to this apparent paradox is that a
      season-specific increase in sensitivity to hormones in brain areas associated
      with aggression offsets low levels of gonadal hormones during periods of
      reproductive quiescence.To test this hypothesis, we manipulated photoperiod to
      induce natural fluctuations in seasonal phenotype across multiple stages of the
      annual reproductive cycle in female Siberian hamsters that display increased
      aggression during short-day reproductive quiescence, suggesting that behaviour
      persists independent of gonadal steroids.Females were housed in long "summer"
      days or short "winter" days for 10, 24 or 30 weeks to capture gonadal regression,
      transition back to a reproductively functional state and full gonadal
      recrudescence, respectively.Long-day animals maintained reproductive
      functionality and displayed low aggression across all time points. By week 10,
      short-day reproductively responsive females underwent gonadal regression and
      displayed increased aggression; non-responsive animals showed no such changes. At
      week 24, animals were in a transitional period and displayed an intermediate
      phenotype with respect to reproduction and aggression. By week 30, short-day
      females were fully recrudesced and returned to long-day-like levels of
      aggression.Consistent with our hypothesis, gonadally regressed females displayed
      decreases in 17beta-oestradiol (oestradiol) levels, but site-specific increases
      in the abundance of brain oestrogen receptor-alpha (ERalpha) in regions
      associated with aggression, but not reproduction. Increased site-specific ERalpha
      may function as a compensatory mechanism to allow increased responsiveness to
      oestradiol in regulating aggression in lieu of high circulating concentrations of
      hormones.Collectively, these results broaden our understanding of how breeding
      phenology maps onto social behaviour and the mechanisms that have evolved to
      coordinate behaviours that occur in non-breeding contexts.

PMID- 28757673
TI  - Contextualizing Disparities: The Case for Comparative Research on Social
      Inequalities in Health.
AB  - PURPOSE: Research on healthcare disparities is making important descriptive and
      analytical strides, and the issue of disparities has gained the attention of
      policymakers in the US, other nation-states, and international organizations.
      Still, disparities scholarship remains US-centric and too rarely takes a cross
      national comparative approach to answering its questions. The US-centricity of
      disparities research has fostered a fixation on race and ethnicity that, although
      essential to understanding health disparities in the United States, has truncated
      the range of questions researchers investigate. In this article, we make a case
      for comparative research that highlights its ability to identify the
      institutional factors may affect disparities. METHODOLOGY/APPROACH: We discuss
      the central methodological challenges to comparative research. After describing
      current solutions to such problems, we use data from the World Values Survey to
      show the impact of key social fault lines on self-assessed health in Europe and
      the U.S. FINDINGS: The negative impact of SES on health is more generalizable
      across context, than the impact of race/ethnicity or gender. RESEARCH
      LIMITATIONS/IMPLICATIONS: Our analysis includes a limited number of countries and
      relies on one measure of health. ORIGINALITY/VALUE OF PAPER: The paper represents
      a first step in a research agenda to understand health inequalities within and
      across societies.

PMID- 28757674
TI  - Enabling Quantitative Optical Imaging for In-die-capable Critical Dimension
      Targets.
AB  - Dimensional scaling trends will eventually bring semiconductor critical
      dimensions (CDs) down to only a few atoms in width. New optical techniques are
      required to address the measurement and variability for these CDs using
      sufficiently small in-die metrology targets. Recently, Qin et al. [Light Sci
      Appl, 5, e16038 (2016)] demonstrated quantitative model-based measurements of
      finite sets of lines with features as small as 16 nm using 450 nm wavelength
      light. This paper uses simulation studies, augmented with experiments at 193 nm
      wavelength, to adapt and optimize the finite sets of features that work as in-die
      capable metrology targets with minimal increases in parametric uncertainty. A
      finite element based solver for time-harmonic Maxwell's equations yields two- and
      three-dimensional simulations of the electromagnetic scattering for optimizing
      the design of such targets as functions of reduced line lengths, fewer number of
      lines, fewer focal positions, smaller critical dimensions, and shorter
      illumination wavelength. Metrology targets that exceeded performance requirements
      are as short as 3 MUm for 193 nm light, feature as few as eight lines, and are
      extensible to sub-10 nm CDs. Target areas measured at 193 nm can be fifteen times
      smaller in area than current state-of-the-art scatterometry targets described in
      the literature. This new methodology is demonstrated to be a promising
      alternative for optical model-based in-die CD metrology.

PMID- 28757675
TI  - Association of GCLM -588C/T and GCLC -129T/C Promoter Polymorphisms of Genes
      Coding the Subunits of Glutamate Cysteine Ligase with Ischemic Heart Disease
      Development in Kazakhstan Population.
AB  - BACKGROUND: Glutamate cysteine ligase (GCL) is a rate-limiting enzyme in
      synthesis of glutathione. Evidence suggests that genetic variations in the
      promoter region of genes coding a catalytic subunit (GCLC -129T/C) and a modifier
      subunit (GCLM -588C/T) of GCL have a functional impact on their transcriptional
      activity and were associated with various disorders. Hence, we hypothesize
      whether these two polymorphic variants of GCLM and GCLC genes are associated with
      the risk of ischemic heart disease (IHD) development in the population of
      Kazakhstan. METHODS: We evaluated 360 patients with IHD and 341 control subjects.
      Allele frequencies of studied promoters' polymorphisms were detected by PCR-RFLP
      analysis. Multiple logistic regression analysis was applied to assess the risk
      for different genotypes obtained. RESULTS: The presence of -588T allele in GCLM
      and -129T allele in GCLC gene genotypes was associated with an increased risk of
      IHD (GCLM -588T: OR = 3.92, p = 0.003; GCLC -129T: OR = 3.22, p = 0.03) for
      general ethnically mixed group. Analysis of each ethnical groups separately
      showed the higher risk tendency for Kazakhs as for GCLM -588T (OR = 4.79; p =
      0.03) and as for GCLC -129T (OR = 4.79, p = 0.03). For Russians, statistically
      differences for two polymorphisms were not observed. CONCLUSION: The two promoter
      polymorphisms of GCLM (-588C/T) and GCLC (-128T/C) are associated with an
      increased risk of IHD in Kazakhstan population.

PMID- 28757676
TI  - Structure and Function of Enterocyte in Intrauterine Growth Retarded Pig
      Neonates.
AB  - The intestine of intrauterine growth retarded (IUGR) neonates showed different
      morphology compared to neonates born with normal body weight (NBW). The aim of
      the present study was to investigate the ultrastructure and proteomic profile of
      the gut epithelium in IUGR pig neonates with special attention to the digestive
      and absorptive function. Intestine tissue samples were investigated in 7-day-old
      IUGR and NBW littermate piglets using histometry, immunofluorescence, scanning
      electron microscopy (SEM), and mass spectrometry analysis. IUGR piglets have
      shown reduced mucosa and muscularis thickness and an enhanced number of foetal
      type enterocytes (FTE). SEM studies have shown the lack of the characteristic
      large-size vacuole in IUGR's enterocytes. Delayed removal of FTE in IUGR neonates
      was probably due to the inhibited apoptosis in the apical part of villi and
      increased apoptosis and reduced mitosis in the crypt region. In the expression of
      proteins in the intestinal mucosa such as hexokinase I, histones, and prelamin
      A/C, carbamoyl phosphate was reduced in IUGR neonates. Finally, IUGR intestines
      showed higher expression of HSPA9 and HSPA5 as apoptosis markers. The data
      indicate modifications of gut mucosa in IUGRs that may result in slower gut
      mucosa maturation and reduced utilisation of nutrient as compared to NBW pig
      neonates.

PMID- 28757677
TI  - Circulating Th1, Th2, and Th17 Levels in Hypertensive Patients.
AB  - BACKGROUND: Evidence from experimental studies showed that Th1, Th2, and Th17
      play a pivotal role in hypertension and target organ damage. However, whether
      changes in the circulating Th1, Th2, and Th17 levels are associated with
      nondipper hypertension and carotid atherosclerotic plaque in hypertension has yet
      to be investigated. METHODS: Th1, Th2, and Th17 levels were detected using a flow
      cytometric analysis, and their related cytokines were measured by enzyme-linked
      immunosorbent assay in 45 hypertensive patients and 15 normotensive subjects.
      RESULTS: The frequencies of Th1 and Th17 in hypertensive patients, especially in
      nondipper patients and patients with carotid atherosclerotic plaque, were
      markedly higher than those in the control group; this was accompanied by higher
      IFN-gamma and IL-17 levels. In contrast, the Th2 frequencies and IL-4 levels in
      hypertensive patients, especially in nondipper patients and patients with carotid
      atherosclerotic plaque, were significantly lower than those in the control group.
      CONCLUSIONS: The changes in Th1, Th2, and Th17 activity are associated with the
      onset of the nondipper type and carotid atherosclerotic plaque in hypertensive
      patients.

PMID- 28757678
TI  - MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot
      Study.
AB  - BACKGROUND: The identification of diagnostic/prognostic biomarkers for asbestos
      related diseases is relevant for early diagnosis and patient survival and may
      contribute to understanding the molecular mechanisms underlying the disease
      development and progression. AIMS: To identify a pattern of miRNAs as possible
      diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and
      asbestosis (ASB) and as prognostic biomarkers for MPM patients. METHODS: miRNA
      16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin
      fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles
      compared to patients with other noncancerous pulmonary diseases (controls).
      Results. The expression of all the miRNAs was significantly lower in patients
      with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in
      plasma and tissue of MPM patients were significantly correlated. Furthermore, the
      expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was
      positively related with cumulative survival in MPM patients. CONCLUSIONS: All the
      miRNA levels were decreased in patients with MPM or ASB, supporting the role of
      circulating miRNAs as a potential tool for diseases associated with exposure to
      asbestos fibers. miRNA-16 was directly related to MPM patient prognosis,
      suggesting its possible use as a prognostic marker in MPM patients.

PMID- 28757680
TI  - Parallel Algorithms for Switching Edges in Heterogeneous Graphs.
AB  - An edge switch is an operation on a graph (or network) where two edges are
      selected randomly and one of their end vertices are swapped with each other. Edge
      switch operations have important applications in graph theory and network
      analysis, such as in generating random networks with a given degree sequence,
      modeling and analyzing dynamic networks, and in studying various dynamic
      phenomena over a network. The recent growth of real-world networks motivates the
      need for efficient parallel algorithms. The dependencies among successive edge
      switch operations and the requirement to keep the graph simple (i.e., no self
      loops or parallel edges) as the edges are switched lead to significant challenges
      in designing a parallel algorithm. Addressing these challenges requires complex
      synchronization and communication among the processors leading to difficulties in
      achieving a good speedup by parallelization. In this paper, we present
      distributed memory parallel algorithms for switching edges in massive networks.
      These algorithms provide good speedup and scale well to a large number of
      processors. A harmonic mean speedup of 73.25 is achieved on eight different
      networks with 1024 processors. One of the steps in our edge switch algorithms
      requires the computation of multinomial random variables in parallel. This paper
      presents the first non-trivial parallel algorithm for the problem, achieving a
      speedup of 925 using 1024 processors.

PMID- 28757679
TI  - Acoustic ranging in poison frogs-it is not about signal amplitude alone.
AB  - ABSTRACT: Acoustic ranging allows identifying the distance of a sound source and
      mediates inter-individual spacing and aggression in territorial species. Birds
      and mammals are known to use more complex cues than only sound pressure level
      (SPL), which can be influenced by the signaller and signal transmission in non
      predictable ways and thus is not reliable by itself. For frogs, only SPL is
      currently known to mediate inter-individual distances, but we hypothesise that
      the strong territoriality of Dendrobatids could make the use of complex cues for
      ranging highly beneficial for this family. Therefore, we tested the ranging
      abilities of territorial males of Allobates femoralis (Dendrobatidae,
      Aromobatinae) in playback trials, using amplitude-normalized signals that were
      naturally degraded over distance, and synthetic signals that were masked with
      different levels of noise. Frogs responded significantly less to signals recorded
      from larger distances, regardless of SPL and signal-to-noise ratio (SNR), but
      showed no differential response to natural minimum and maximum SNRs across the
      typical communication range in wild populations. This indicates that frogs used
      signal amplitude and SNR only as ancillary cues when assessing the distance of
      sound sources and relied instead mainly on more complex cues, such as spectral
      degradation or reverberation. We suggest that this ability mediates territorial
      spacing and mate choice in A. femoralis. Good ranging abilities might also play a
      role in the remarkable orientation performance of this species, probably by
      enabling the establishment of a mental acoustic map of the habitat. SIGNIFICANCE
      STATEMENT: Acoustic ranging allows the distance of vocalizing competitors and
      mates to be identified. While birds and mammals are known to use complex cues
      such as temporal degradation, frequency-dependent attenuation and reverberation
      for ranging, previous research indicated that frogs rely only on signal amplitude
      (sound pressure level) to assess the distance of other callers. The present study
      shows for the first time that also poison frogs can make use of more complex
      cues, an ability which is likely to be highly beneficial in their territorial
      social organization and probably can also be used for orientation.

PMID- 28757681
TI  - Pilot Study of a Group-Based Psychosocial Trauma Recovery Program in Secure
      Accommodation in Scotland.
AB  - The current study is the first to implement and evaluate a group-based trauma
      specific program for adolescents in a secure accommodation facility in Scotland.
      A randomized control and qualitative pilot study compared an intervention group
      (n = 10), who received Teaching Recovery Techniques, to a waitlist control group
      (n = 7). Measures included subjective units of disturbance (SUDs), standardized
      trauma symptom questionnaires, and analysis of behavior monitoring logs.
      Adolescent interviews (n = 10) and a presenter focus group (n = 4) assessed
      program experience and views on future development. Sessions were videoed and
      analyzed for program adherence. Analysis involved MANOVA, and a quasi-qualitative
      thematic approach for participant views. Adolescents reported high SUDs and a
      range of trauma symptoms. A large effect size was found for reduced SUDs (d =
      1.10) and positive trends were identified for symptoms and behavior change in the
      intervention group. Program adaptations included smaller groups, the use of
      visual materials and liaison with care staff to facilitate generalization.
      Recommendations are made for program development and large scale evaluation.

PMID- 28757682
TI  - High-precision measurement of the X-ray Cu Kalpha spectrum.
AB  - The structure of the X-ray emission lines of the Cu Kalpha complex has been
      remeasured on a newly commissioned instrument, in a manner directly traceable to
      the Systeme Internationale definition of the meter. In this measurement, the
      region from 8000 eV to 8100 eV has been covered with a highly precise angular
      scale, and well-defined system efficiency, providing accurate wavelengths and
      relative intensities. This measurement updates the standard multi-Lorentzian-fit
      parameters from Hartwig, Holzer, et al., and is in modest disagreement with their
      results for the wavelength of the Kalpha1 line when compared via quadratic
      fitting of the peak top; the intensity ratio of Kalpha1 to Kalpha2 agrees within
      the combined error bounds. However, the position of the fitted top of Kalpha1 is
      very sensitive to the fit parameters, so it is not believed to be a robust value
      to quote without further qualification. We also provide accurate intensity and
      wavelength information for the so-called Kalpha3,4 "satellite" complex.
      Supplementary data is provided which gives the entire shape of the spectrum in
      this region, allowing it to be used directly in cases where simplified, multi
      Lorentzian fits to it are not sufficiently accurate.

PMID- 28757684
TI  - Evaluation of Metalloproteinase-8 Levels in Crevicular Fluid of Patients with
      Healthy Implants or Periodontitis.
AB  - Evaluation of periodontal and peri-implant tissue condition is mainly based on
      clinical examination and imaging diagnostics. Some data imply that
      Metalloproteinase-8 (MMP-8) level examination in peri-implant sulcular fluid
      (PISF) might be useful for evaluating the condition of peri-implant tissues and
      monitoring a development of peri-implant inflammation, including both mucositis
      and peri-implantitis. Hence, in this study, we decided to evaluate the level of
      MMP-8 in PISF obtained from patients without clinical symptoms of mucositis or
      peri-implantitis and compare it with MMP-8 level in gingival crevicular fluid
      (GCF) obtained from patients with healthy periodontium and those with varying
      severity of periodontitis. A total of 189 subjects were included in the study,
      and GCF/PISF samples were analysed for MMP-8 level by ELISA test. We documented
      that MMP-8 level in PISF obtained from patients without symptoms of mucositis or
      peri-implantitis was significantly higher not only than in GCF of periodontally
      healthy patients but also, which seems to be very interesting, than in GCF of
      patients with varying degrees of periodontal inflammation, consistent with
      earlier studies. Our observation might imply that monitoring of MMP-8 level in
      PISF could help to diagnose mucositis/peri-implantitis in an early stage, prior
      to clinical manifestations, which may allow for quick start of appropriate
      therapy.

PMID- 28757685
TI  - Immunometabolism: Molecular Mechanisms, Diseases, and Therapies 2016.

PMID- 28757683
TI  - Chemokines (CCL3, CCL4, and CCL5) Inhibit ATP-Induced Release of IL-1beta by
      Monocytic Cells.
AB  - Chemokines and ATP are among the mediators of inflammatory sites that can enter
      the circulation via damaged blood vessels. The main function of chemokines is
      leukocyte mobilization, and ATP typically triggers inflammasome assembly. IL
      1beta, a potent inflammasome-dependent cytokine of innate immunity, is essential
      for pathogen defense. However, excessive IL-1beta may cause life-threatening
      systemic inflammation. Here, we hypothesize that chemokines control ATP-dependent
      secretion of monocytic IL-1beta. Lipopolysaccharide-primed human monocytic U937
      cells were stimulated with the P2X7 agonist BzATP for 30 min to induce IL-1beta
      release. CCL3, CCL4, and CCL5 dose dependently inhibited BzATP-stimulated release
      of IL-1beta, whereas CXCL16 was ineffective. The effect of CCL3 was confirmed for
      primary mononuclear leukocytes. It was blunted after silencing CCR1 or calcium
      independent phospholipase A2 (iPLA2) by siRNA and was sensitive to antagonists of
      nicotinic acetylcholine receptors containing subunits alpha7 and alpha9. U937
      cells secreted small factors in response to CCL3 that mediated the inhibition of
      IL-1beta release. We suggest that CCL chemokines inhibit ATP-induced release of
      IL-1beta from U937 cells by a triple-membrane-passing mechanism involving CCR,
      iPLA2, release of small mediators, and nicotinic acetylcholine receptor subunits
      alpha7 and alpha9. We speculate that whenever chemokines and ATP enter the
      circulation concomitantly, systemic release of IL-1beta is minimized.

PMID- 28757687
TI  - Facing the epidemic of myopia: Exploring the possibilities.

PMID- 28757686
TI  - Acinetobacter baumannii Lipopolysaccharide Influences Adipokine Expression in 3T3
      L1 Adipocytes.
AB  - Acinetobacter baumannii is one of the most important nosocomial opportunistic
      pathogen worldwide. In addition, obesity has been associated with an increased
      risk of nosocomial infection, suggesting that there may be an association between
      A. baumannii and white adipose tissue. However, the effects of A. baumannii on
      adipocytes have not been well studied at the molecular level. Here, we
      investigated the potential role of A. baumannii-derived lipopolysaccharides (LPS)
      as signaling molecules that affect adipocyte functionality. We tested the effect
      of increasing concentrations of A. baumannii-derived LPS (10, 100, or 1000 ng/mL)
      on the 3T3-L1 adipocyte cell line. Exposure to LPS was found to increase the
      expression of several adipokines (e.g., MIP-2, MCP-1, TNF-alpha, IL-6, lipocalin
      2, and FABP4) in 3T3-L1 adipocytes and significantly reduced the expression of
      leptin and adiponectin. The effects of A. baumannii-derived LPS on MIP-2
      expression were similar in comparison with that of LPS prepared from Pseudomonas
      aeruginosa and Escherichia coli in our cell culture-based system. This study
      suggests that A. baumannii-derived LPS functions as a signaling molecule that
      impacts the inflammatory function of white adipose tissue on the level of gene
      expression.

PMID- 28757688
TI  - Ocular trauma: A tertiary hospital experience from Oman.
AB  - PURPOSE: To describe the epidemiology of ocular trauma in a tertiary hospital
      setting in Muscat, Oman. METHODS: Medical records of all cases of ocular trauma
      which presented to the Emergency Department at Al-Nahdha Hospital and were seen
      by the ophthalmology service from January 1, 2013 to June 30, 2013 (6 months)
      were reviewed to collect data on ocular trauma according to the World Eye Injury
      Registry initial reporting form which uses the Birmingham Eye Trauma Terminology
      System. RESULTS: There were 27,951 patients seen at the Emergency Department and
      611 of which were ocular trauma cases (cumulative incidence 2.2% [confidence
      interval 2.0-2.4]). The mean age of the patients was 23 years and males comprised
      the majority of the cases (72%). Thirty-two patients had bilateral injury giving
      a total of 643 eyes injured. More than half of all injuries were caused by either
      blunt or large sharp objects. The cornea was the most frequently injured tissue
      (49%), but most injuries were minor in nature. More than three quarters (77%) of
      all eyes had a visual acuity of 0.3 (LogMAR) or better on presentation. There
      were 35 eyes (6%) with open globe injuries (OGI) and three-quarters of them
      occurring in the manual laborers. CONCLUSION: Ocular trauma is a common
      presentation at Al-Nahdha Hospital. Although the majority of trauma cases were
      minor without any visual disability sequelae, OGI could have been prevented with
      better ocular protection in the workplace.

PMID- 28757689
TI  - Management outcome(s) in eyes with retinoblastoma previously inadequately treated
      with systemic chemotherapy alone without focal therapy.
AB  - OBJECTIVE: The objective of this study was to evaluate the outcome of management
      in eyes with intraocular retinoblastoma (RB) that had received inadequate initial
      therapy (chemotherapy without focal therapy) before eventually receiving
      necessary consolidation therapy at a tertiary referral center. METHODS: A
      retrospective observational case series of 30 eyes from 26 RB patients who had
      initially received systemic chemotherapy as a sole therapy. The main outcome
      measures were demographics, laterality, International Classification of RB
      (ICRB), treatments, tumor control, and survival. RESULTS: The median age at
      diagnosis was 24 months and the median delay between time at diagnosis and time
      at referral to a tertiary center that has adequate focal therapy for RB was 9.5
      months (range 5-20 months). Sixteen (62%) patients were monocular from
      enucleation of the contralateral eye. Features of ICRB Group A tumors were seen
      in 3 (10%) eyes, Group B in 7 (23%) eyes, Group C in 2 (7%) eyes, Group D in 16
      (53%) eyes, and Group E in 2 (7%) eyes. Eighteen (69%) patients required more
      systemic chemotherapy (median, 4.4 cycles; range, 2-8 cycles), and 8 (26%) eyes
      received local chemotherapy (subtenon, intravitreal, or intra-arterial). All
      treated eyes received consolidation therapy as transpupillary thermotherapy
      and/or cryotherapy. Radioactive plaque therapy was used in 1 (3%) eye and
      external beam radiation therapy in 3 (10%) eyes. At a mean follow-up of 13 months
      (median, 11.5 months; range, 9-27 months), enucleation was avoided in 25 (83%)
      eyes. Two (7%) eyes were enucleated initially, and 3 (10%) were enucleated after
      failure of additional therapy. Twenty-three (77%) eyes did not show any viable
      tumor after a median of 11.5 months of follow-up after the last treatment, and 2
      (7%) eyes still have residual tumor recurrences that need more consolidation
      focal therapy. CONCLUSION: Chemotherapy alone cannot eradicate RB cells in
      effected eyes without combination with consolidation therapy by a
      multidisciplinary team to salvage the affected eye as well as its vision.
      Nonetheless, chemotherapy can be initiated (to keep the tumor at a less invasive
      stage) for patients from centers or countries where combination therapy is not
      available until they gain access to adequate management of RB.

PMID- 28757690
TI  - Prognostic preoperative factors for successful outcome of surgery in horizontal
      strabismus.
AB  - CONTEXT: Surgery for horizontal strabismus reportedly has a success rate of 60%
      80%. However, which preoperative factors are predictive of this success is not
      clear. AIMS: To identify prognostic factors those are predictive of successful
      outcome in horizontal strabismus surgery. SETTINGS AND DESIGN: Observational
      analytical study using multiple logistic regression (MLR). SUBJECTS AND METHODS:
      We assessed the medical records of patients who had undergone first-time
      horizontal muscle strabismus surgery between 2002 and 2013, where complete follow
      up data were available for >=6 weeks, and also, we collected data prospectively
      on patients operated between January 2014 and September 2015. Successful outcome
      was defined as a postoperative angle of deviation within 10 prism diopter of
      orthophoria at >=6 weeks postoperatively. Independent variables considered were
      age at onset, age at surgery, duration, gender, deviation - type and amount,
      logMAR visual acuity (VA) - mean and of the poorer eye, mean refractive error,
      amount of anisometropia, and presence of dense amblyopia. Only those with P < 0.2
      on univariate analyses (UAs) were included in the MLR, with significance set at P
      <= 0.05. STATISTICAL ANALYSES: UA (Chi-square for categorical variables and t
      tests for continuous variables), followed by logistic regression analysis.
      RESULTS: Of 113 patients, on UA, type of deviation (P = 0.01), age at surgery (P
      = 0.16), absence of dense amblyopia (P = 0.002), and logMAR VA of the poorer eye
      (P = 0.005) qualified for the inclusion in MLR. On MLR, esotropia (ET) (odds
      ratio [OR]: 4.46) and absence of dense amblyopia (OR: 5.90) were associated with
      success. CONCLUSIONS: With an overall success rate of 83%, ET and absence of
      dense amblyopia were significantly predictive of surgical success.

PMID- 28757691
TI  - Cut-and-place technique of pterygium excision with autograft without using
      sutures or glue: Our experience.
AB  - BACKGROUND: Conjunctival sutures used in pterygium surgery are not only time
      consuming process but also may lead to local complications such as discomfort,
      scarring, granuloma, or infection. Plasma-derived products such as fibrin glue
      may produce possible hypersensitivity reactions whereas the risk of viral
      transmission remains theoretically possible. We describe a simple method of
      achieving conjunctival autograft adherence during pterygium surgery avoiding
      potential complications associated with the use of fibrin glue or sutures.
      MATERIALS AND METHODS: After pterygium excision and fashioning of the autologous
      conjunctival graft, the recipient bed is encouraged to achieve natural hemostasis
      and relative desiccation before graft placement. Excessive hemorrhage in the
      graft bed is tamponed. Graft adherence and positioning is examined 12-15 min
      after surgery. RESULTS: A total of 205 cases of pterygium underwent excision with
      conjunctival autograft without using sutures or glue. Mean follow-up time was
      14.6 months. Cosmesis achieved was excellent in all cases. There were no
      intraoperative complications seen. Recurrence was seen in 6.8% of cases (14
      cases). Nasal gaping was seen in 36% of cases (74 cases), which healed
      spontaneously without any surgical intervention. CONCLUSION: This simple
      technique for pterygium surgery is not only cost effective and quick but also may
      prevent potential adverse reactions encountered with the use of foreign materials
      and in this large series provided safe and comparable results to current methods.

PMID- 28757692
TI  - Orbital implant exposure following enucleation or evisceration.
AB  - PURPOSE: To study the exposure rate of orbital implant postenucleation or
      evisceration procedures in two tertiary hospitals in Oman. DESIGN: A
      retrospective, descriptive, cross-section study. MATERIALS AND METHODS: Patients'
      records were reviewed for patients' demographics, surgical indications, implant
      types, follow-up and any reported complications after surgeries. Patients with a
      minimum of 1 year follow-up period were selected. All patients who underwent
      enucleation or evisceration with primary orbital implant were included in the
      study. Patients who underwent secondary orbital implant were excluded from the
      study. RESULTS: A total of 37 patients (age between 4 and 88-year-old, median age
      is 54-year-old) underwent enucleation or evisceration during 2008-2014. The most
      common indications for the surgical intervention were painful blind eye (35%),
      followed by trauma (16%), and perforated corneal ulcer (16%). Out of 37 patients,
      hydroxyapatite implant was implanted in 17 patients (46%), a glass or acrylic
      implant was implanted in 17 patients (46%), bioceramic implant was implanted in
      two patients (5%), and Molteno prosthesis was implanted in one patient (3%).
      There was no case of orbital implant exposure in any patients in this study.
      CONCLUSIONS: No orbital implant exposure was recorded in this study. The surgical
      technique, end to end rectus muscles suturing, used for enucleation/evisceration
      was the main reason for reduced implant exposure. In addition, the preexisting
      ocular pathology did not affect the outcome of the study.

PMID- 28757693
TI  - Effect of phacoemulsification on measurement of retinal nerve fiber layer and
      optic nerve head parameters using spectral-domain-optical coherence tomography.
AB  - PURPOSE: The purpose of this study is to determine the effect of
      phacoemulsification cataract extraction on measurement of retinal nerve fiber
      layer and optic nerve head parameters using spectral domain optical coherence
      tomography. MATERIAL AND METHODS: A prospective, hospital-based study of 100
      patients of 40 years of age and above, with no other ocular morbidity except
      cataract and planned for phacoemulsification with IOL implantation (SN60WF) at a
      tertiary centre at AIIMS, New Delhi, India. All patients underwent imaging with
      Cirrus SD-OCT model 400 and the optic disc cube 200x200 protocol at baseline and
      at 1 month follow up. Paired sample t-test was used to compare the RNFL
      parameters and ONH parameters. RESULTS: The mean age of subjects was 56.6 +/-
      12.3 years (70 males, 30 females). The average RNFL increased from 92.6 +/- 5.4
      MUm to 101.3 +/- 5.6 MUm after phacoemulsification, an increase of 9% (P = 0.003)
      and the signal strength increased from 5.6 +/- 0.5 to 7.6 +/- 0.7, increasing by
      35.7% (P = 0.004). There was a significant increase in the disc area (P = 0.004)
      and rim area (P = 0.004) but no significant change in vertical cup-disc ratio (P
      = 0.45) or average cup-disc ratio (P = 0.075). The quadrant-wise RNFL thickness
      increase in inferior, superior, nasal, and temporal quadrants was 12.6% (P =
      0.001), 10% (P = 0.001), 5.6% (P = 0.001), and 3.2% (P = 0.001), respectively.
      The change in RNFL thickness was maximum in posterior subcapsular cataract (P =
      0.001) followed by cortical (P = 0.001) and nuclear (P = 0.001) subtypes.
      CONCLUSIONS: A significant increase in RNFL thickness and signal strength was
      observed after cataract surgery using SD-OCT. The maximum change in RNFL
      thickness was in the inferior quadrant, where RNFL thinning is a significant
      predictor of glaucoma progression. The posterior subcapsular cataract interfered
      with RNFL measurement maximally due to its density and proximity to nodal point.
      After the cataract surgery, a new baseline needs to be established by obtaining
      fresh OCT images for assessing the longitudinal follow-up of a glaucoma patient.

PMID- 28757694
TI  - Evaluation of a new electronic preoperative reference marker for toric
      intraocular lens implantation by two different methods of analysis: Adobe
      Photoshop versus iTrace.
AB  - PURPOSE: The aim of this study is to compare two different methods of analysis of
      preoperative reference marking for toric intraocular lens (IOL) after marking
      with an electronic marker. SETTING/VENUE: Cataract and IOL Implantation Service,
      Shroff Eye Centre, New Delhi, India. PATIENTS AND METHODS: Fifty-two eyes of
      thirty patients planned for toric IOL implantation were included in the study.
      All patients had preoperative marking performed with an electronic preoperative
      two-step toric IOL reference marker (ASICO AE-2929). Reference marks were placed
      at 3-and 9-o'clock positions. Marks were analyzed with two systems. First, slit
      lamp photographs taken and analyzed using Adobe Photoshop (version 7.0). Second,
      Tracey iTrace Visual Function Analyzer (version 5.1.1) was used for capturing
      corneal topograph examination and position of marks noted. Amount of alignment
      error was calculated. RESULTS: Mean absolute rotation error was 2.38 +/- 1.78
      degrees  by Photoshop and 2.87 +/- 2.03 degrees  by iTrace which was not
      statistically significant (P = 0.215). Nearly 72.7% of eyes by Photoshop and
      61.4% by iTrace had rotation error <=3 degrees  (P = 0.359); and 90.9% of eyes by
      Photoshop and 81.8% by iTrace had rotation error <=5 degrees  (P = 0.344). No
      significant difference in absolute amount of rotation between eyes when analyzed
      by either method. CONCLUSIONS: Difference in reference mark positions when
      analyzed by two systems suggests the presence of varying cyclotorsion at
      different points of time. Both analysis methods showed an approximately 3 degrees
      of alignment error, which could contribute to 10% loss of astigmatic correction
      of toric IOL. This can be further compounded by intra-operative marking errors
      and final placement of IOL in the bag.

PMID- 28757695
TI  - Iatrogenic subretinal injection of Ozurdex(r) implant and its effect on macular
      edema.
AB  - PURPOSE: The purpose of this study was to report a rare case of subretinal
      lodgement of Ozurdex(r) implant (Allergan Inc., Irvine, CA, USA) and its effect
      on macular edema in a case of central retinal vein occlusion (RVO). METHODS: A
      rare complication of subretinal lodgement of Ozurdex(r) implant without retinal
      perforation was encountered in a case of RVO with intractable macular edema. As
      associated retinal perforation was not noted, no intervention was done. The
      patient was regularly followed up at 1 month, and the effect on macular edema and
      intraocular pressure was analyzed. RESULTS: The corticosteroid pellets got
      disintegrated and totally absorbed with a subtle chorioretinal scar by the 3rd
      follow-up month without any intervention. Even though subretinal, it was capable
      of reducing macular edema by 181 microns at 1 month postinjection, and its effect
      started wearing off by 2 months. DISCUSSION: Subretinal lodgement of Ozurdex(r)
      implant is rare and preventable, yet a potential complication of intravitreal
      implants which is now in vogue. We speculate a too acute angle of injection or
      incomplete insertion of the drug delivery system applicator (DDS) away from the
      limbus or perhaps less refined previous DDS applicator to be a cause for
      subretinal delivery of the implant. The early disintegration of implant occurred
      due to breach in structural integrity that caused loss of controlled drug release
      and rapid absorption. It reduced macular edema up to 2 months without elevating
      intraocular pressure. CONCLUSION: A more widespread application of any technology
      always portends a more significant risk for complications, and an ophthalmologist
      should be aware of this potential risk. Though subretinal, corticosteroid implant
      was capable of reducing macular edema by 181 microns by 1 month and its effect
      wore off by 2 months.

PMID- 28757696
TI  - Can pneumocephalus present as flashes of light? A rare case report.
AB  - Orbital emphysema and associated pneumocephalus usually result from trauma to
      orbital bones or due to sinus disease, allowing air to travel from paranasal
      sinus into orbit and brain. However, it is extremely rare to have orbital
      emphysema and pneumocephalus in the absence of orbital wall fracture. In our
      case, a young male was admitted with severe eye pain, diminution of vision due to
      sudden exposure of compressed air gun. Examination revealed proptosed,
      emphysematous right eye with conjunctival laceration. Computed tomography scan of
      the head and orbit revealed multiple radiolucencies with air in the right orbit
      and brain extending up to the spinal canal without any evidence of orbital sinus
      or cranial bone fracture. Visual acuity recovered completely on follow-up;
      however, 2 weeks following injury, the patient developed disabling flashes of
      light which the patient perceived as central in location and resolved finally
      over a period of 3 months. Flashes of light, in our case, could be attributable
      to unnoticed damage to cerebral vasculature or connective tissue surrounding the
      optic nerve due to pneumocephalus.

PMID- 28757697
TI  - Corneal ring infiltration in contact lens wearers.
AB  - To report a case of atypical sterile ring infiltrates during wearing soft
      silicone hydrogel contact lens due to poor lens care. A 29-year-old woman
      presented with complaints of pain, redness, and morning discharge. She was
      wearing soft silicone hydrogel contact lens previously; her current symptoms
      began 1 week before presentation. On examination, best-corrected visual acuity
      was 20/40 in that eye. Slit-lamp examination revealed dense, ring-shaped
      infiltrate involving both the superficial and deep stromal layers with lucid
      interval to the limbus, edema of the epithelium, epithelial defect, and
      vascularization of the superior limbus. Cornea-specific in vivo laser confocal
      microscopy (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT 2-RCM,
      Heidelberg Engineering GmbH, Dossenheim, Germany) revealed Langerhans cells and
      no sign of Acanthamoeba or fungal features, using lid scraping and anti
      inflammatory drops; her vision completely recovered. We reported an atypical case
      of a sterile corneal ring infiltrate associated with soft contact lens wearing;
      smear, culture, and confocal microscopy confirmed a sterile inflammatory
      reaction.

PMID- 28757698
TI  - The nomadic Ozurdex(r): Anterior migration of the dexamethasone implant and back!
AB  - Dexamethasone intravitreal implantation has been used in various retinal and
      uveal pathologies. Common complications include cataract formation and raised
      intraocular pressure. Although uncommon, migration of the implant has also been
      well reported. We describe a case with migration of the implant into the anterior
      chamber in a patient with a scleral-fixated intraocular lens, which was managed
      noninvasively by pupillary dilatation and positioning of the patient.

PMID- 28757699
TI  - Coats' disease with retinochoroidal anastomosis.
AB  - A 4-year-old girl presented with decreased vision since 3 months. Visual acuity
      was 20/20 in right eye and counting fingers at 2 meters in the left. Left eye
      examination revealed exotropia, retinal telangiectasia, extensive subretinal
      exudation over the macula and exudative retinal detachment suggestive of Coats'
      disease. Fundus fluoroscein angiography highlighted the hallmark 'light bulb'
      retinal telangiectasias, macular retinochoroidal anstamosis and peripheral
      nonperfused retina. The patient was treated with focal laser photocoagulation to
      the retinal telangiectatic vessels and scatter laser photocoagulation of the non
      perfused retina.

PMID- 28757700
TI  - Brachytherapy and anterior segment imaging in iris melanoma.
AB  - Ultrasound biomicroscopy (UBM) remains a potent tool in the diagnosis and
      characterization of uveal lesions. In the setting of malignancy, it can confirm
      both placement of and response to brachytherapy. We present a case of iris
      melanoma with aggressive BAP-1 mutation, treated successfully with I-131
      brachytherapy which was both characterized and followed with UBM and thereafter
      discuss the current state of these modalities.

PMID- 28757701
TI  - Viral mononeurities causing partial oculomotor nerve palsy in an 8 month old
      child.
AB  - BACKGROUND: Palsy of the oculomotor nerve is rarely seen in children, and
      comprehensive guidelines for management and outcome are difficult to find. CASE:
      Here we describe a 8 month old boy with left sided ptosis and infero-leteral
      deviation of left eye and normally reacting pupil and CSF antimeasles antibody
      titre negative. OUTCOME: The ptosis improved within 3 weeks with no residual
      neurodeficit. MESSAGE: Viral mononeuritis leading to partial 3rd nerve palsy is a
      rare entity in children till date.

PMID- 28757702
TI  - Clinical characteristics of Crouzon syndrome.
AB  - Crouzon syndrome (CS) is an genetic disorder with autosomal dominant inheritance
      caused by mutation of the gene for fibroblast growth factor receptor 2 (FGFR2)
      was described as one of the varieties of craniosynostosis. In this presented
      case, premature closure of the sutures had caused restricted skull growth and
      lack of space for the growing brain resulted to shallowed eyes and cranial and
      ophthalmic deformities and impairment in tooth development. Management of a
      patient of CS has two components. First is the release of prematurely fused
      sutures based on evidence of raised intracranial pressure. Surgery is mainly
      carried out early after 3-6 months. Second is the craniofacial reconstructive
      surgery including advancement of the maxilla and frontonasal complex; and other
      surgeries depending upon the deformities. An increased intracranial pressure
      impairs brain development and can lead to mental retardation. Because of the
      delayed diagnosis and treatment in this case, visual and hearing loses and
      decreased mental capacity and mild retardation.

PMID- 28757703
TI  - 45 year old female with decreased vision in left eye.

PMID- 28757704
TI  - Retinopathy in hepatitis C.

PMID- 28757705
TI  - A rare case of bilateral congenital dacryocele.

PMID- 28757706
TI  - Myopic strabismus fixus with endophthalmitis.

PMID- 28757707
TI  - Resolution of acquired Brown syndrome with oral steroid therapy.

PMID- 28757709
TI  - A deduced probable HLA-DRB1*16:35-associated HLA haplotype (A*11-B*13-DRB1*16:35)
      found in a case analysis of two Taiwanese unrelated bone marrow hematopoietic
      stem cell donors.
AB  - OBJECTIVE: HLA-DRB1*16:35 is a low incidence allele in the HLA-DRB1 locus. The
      objective of this study is to report the ethnicity of DRB1*16:35 and its deduced
      probable HLA associated haplotype in two Taiwanese unrelated bone marrow
      hematopoietic stem cell donors and to determine its variation from DRB1*16:02:01
      and DRB1*16:01:01. MATERIALS AND METHODS: A sequence-based typing method was
      employed to confirm the low incidence allele DRB1*16:35. Polymerase chain
      reaction was performed to amplify exon 2 and exon 3 of the HLA-A and HLA-B loci
      and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons
      were sequenced employing BigDye Terminator Cycle Sequencing Ready Reaction kits
      in both directions according to the manufacturer's protocols. RESULTS: The DNA
      sequence of DRB1*16:35 is identical to DRB1*16:02:01 in exons 2, except for
      residue 364 where the C of DRB1*16:02:01 is replaced by the T of DRB1*16:35
      (codon 93, CGG->TGG). The nucleotide exchange leads to an amino acid alteration
      to the protein sequence of DRB1*16:02:01 at residue 93 where the arginine (R) of
      DRB1*16:02:01 is changed to the tryptophan (W) of DRB1*16:35. We deduced the
      probable HLA haplotype in association with DRB1*16:35 in Taiwanese to be A*11
      B*13- DRB1*16:35. CONCLUSION: Information on the deduced probable HLA haplotype
      in association with the low incidence DRB1*16:35 allele that we report here is of
      value for HLA testing laboratories for reference purposes. In addition, it can be
      used by stem cell transplantation donor search coordinators to determine a
      strategy for finding compatible donors in unrelated bone marrow donor registries
      when a patient has this uncommon HLA allele.

PMID- 28757708
TI  - Practical points in the medical treatment of overactive bladder and nocturia in
      the elderly.
AB  - The prevalence of overactive bladder (OAB) increases with age. Degeneration of
      the central nervous system in the elderly has been proposed as one of the
      pathogenic factors of OAB. Antimuscarinic therapy is effective in the treatment
      of OAB; however, intolerable systemic adverse events and cognitive dysfunction
      during treatment with nonselective antimuscarinic agents is of growing concern in
      elderly patients. The newly developed beta-3 adrenoceptor agonist mirabegron does
      not adversely affect flow rate and detrusor pressure, and its therapeutic
      efficacy and tolerability are similar in patients aged > 65 years and > 75 years,
      suggesting it might be the therapeutic choice in older patients with OAB.
      Nocturia can cause sleep deprivation at night and increase daytime sleepiness and
      loss of energy in the elderly. Desmopressin add-on therapy is effective in
      improving nocturia and storage symptoms. However, elderly patients with a
      baseline serum sodium level below the normal range are at high risk of developing
      significant hyponatremia.

PMID- 28757710
TI  - Effects of obesity on the association between common variations in the TBX5 gene
      and matrix metalloproteinase 9 levels in Taiwanese.
AB  - OBJECTIVES: The TBX5 gene, a member of the T-box family, is associated with
      congenital heart disease, electrocardiographic parameters, and development of
      atrial fibrillation in the general population. This study aimed to elucidate the
      role of TBX5 gene polymorphisms in metabolic and inflammatory profiles possibly
      linked to TBX5-related pathologies. MATERIALS AND METHODS: A sample population of
      597 individuals having routine health examinations was enrolled. Five tagging
      TBX5 single nucleotide polymorphisms (SNPs) were analyzed using polymerase chain
      reaction and restriction enzyme digestion or TaqMan SNP genotyping assays.
      Associations between genotypes/haplotypes and matrix metalloproteinase 9 (MMP9)
      levels were investigated using generalized linear model analysis. Interactions
      between each genotype/haplotype, MMP9 level, and obesity status were tested using
      two-way analysis of variance with Golden Helix SVS Win32 7.3.1 software. RESULTS:
      After adjusting for clinical covariates, TBX5 genotypes were found to be
      associated with MMP9 levels (p = 0.002 and p = 0.001 for rs4113925 and rs3825214,
      respectively) in a dominant inheritance model. Haplotype analysis using three tag
      SNPs (rs11067101, rs1247973, and rs3825214) revealed a significant association
      between TBX5 haplotype GCG and MMP9 levels (uncorrected p = 0.0093 and the
      corrected false discovery rate p = 0.0435). Multivariate analysis identified that
      SNP rs3825214, in addition to the MMP9 and E-selectin genotypes, was
      independently associated with MMP9 levels (p < 0.001). Using a dominant
      inheritance model, subgroup and interaction analysis showed associations between
      the rs4113925, rs3825214, and MMP9 levels only in nonobese individuals (p = 1.04
      * 10-4 and p = 7.11 * 10-5, respectively; interaction p = 0.009 and 0.018,
      respectively). Subgroup analysis showed a borderline significant association
      between haplotype GCG and MMP9 levels (uncorrected p = 0.020 and corrected false
      discovery rate p = 0.073), but with no evidence of interaction. CONCLUSION: TBX5
      genotypes/haplotypes are independently associated with MMP9 in Taiwanese
      individuals and occur predominantly in nonobese people. These associations may
      broaden our understanding of the mechanism underlying T-box family gene activity
      and related cardiovascular pathologies.

PMID- 28757711
TI  - Combined expansive open-door laminoplasty with short-segment lateral mass
      instrumented fusion for multilevel cervical spondylotic myelopathy with short
      segment instability.
AB  - OBJECTIVES: Expansive open-door laminoplasty (EOLP) is an effective procedure for
      multilevel cervical spondylotic myelopathy (MCSM). It preserves a higher range of
      cervical motion than laminectomy with fusion and reserves more posterior elements
      than laminectomy alone. MCSM with short-segment instability or correctable local
      kyphosis often requires long-segment decompression and adequate segment fusion.
      MATERIALS AND METHODS: We retrospectively reviewed 20 patients who received EOLP
      with short-segment posterior lateral mass instrumented fusion at our institution
      from 2008 to 2011. The follow-up period was at least 36 months. Postoperative
      functional and radiographic outcomes were collected and analyzed. RESULTS:
      Japanese Orthopedic Association scores improved significantly 36 months after
      surgery and the average recovery ratio was 85.3 +/- 14.7%. Nurick disability
      scores and neck pain visual analog scale scores considerably decreased 3 years
      after surgery. No patients had aggravated neck pain or C5 nerve palsy during
      follow-up. The preservation of range of motion was approximately 60% after 36
      months. No implant loosening or laminar collapse was reported on radiographic
      follow-up. CONCLUSION: EOLP with concomitant lateral mass instrumented fusion
      yields favorable short-term clinical results for MCSM with short segment
      instability.

PMID- 28757712
TI  - Serum osteoprotegerin levels associated with the aortic augmentation index in
      renal transplant recipients.
AB  - OBJECTIVES: Arterial stiffness is recognized as an independent risk factor for
      cardiovascular morbidity and mortality. Recent studies found that osteoprotegerin
      (OPG) is associated with arterial stiffness and may reflect endothelial
      dysfunction. The aim of this study was to evaluate the relationship between
      fasting serum OPG levels and the aortic augmentation index (AIx) in renal
      transplant recipients. MATERIALS AND METHODS: Fasting blood samples were obtained
      from 66 renal transplant recipients. The aortic AIx was measured using a
      validated tonometry system (SphygmoCor). Serum OPG levels were measured using a
      commercial enzyme-linked immunosorbent assay kit. RESULTS: Univariate linear
      analysis of the aortic AIx in renal transplant recipients revealed that body fat
      mass (r = 0.377, p = 0.002), aortic diastolic blood pressure (DBP; r = 0.307, p =
      0.020), triglycerides (r = 0.260, p = 0.035), and logarithmically transformed OPG
      (log-OPG, r = 0.402, p < 0.001) were positively correlated, whereas height (r =
      0.361, p = 0.004) and body weight (r = 0.212, p = 0.041) were negatively
      correlated with the aortic AIx in renal transplant recipients. Multivariate
      forward stepwise linear regression analysis of the factors significantly
      associated with the aortic AIx showed that log-OPG (R2 = 0.213, p < 0.001),
      height (R2 = 0.081, p = 0.009), and aortic DBP (R2 = 0.058, p = 0.022) were
      independent predictors of the aortic AIx in renal transplant recipients.
      CONCLUSION: These results suggest that the serum fasting OPG level is associated
      with the aortic AIx in renal transplant recipients.

PMID- 28757713
TI  - Prognostic factors of paranasal sinusitis with intracranial invasion: A 14-year
      review of cases at Hualien Buddhist Tzu Chi Hospital.
AB  - Intracranial invasion of paranasal sinusitis is an emergency condition that
      requires surgical and medical intervention in order to avoid further
      deterioration. We surveyed patients at the Buddhist Tzu Chi Hospital (Hualien,
      Taiwan) who had paranasal sinusitis with intracranial invasion. A total of 505
      patients with paranasal sinusitis were surveyed at Hualien Buddhist Tzu Chi
      Hospital over a 14-year period (2000-2013). Data on clinical presentations,
      microbiology, host factors, postinterventional morbidity, and postinterventional
      mortality are presented. Of the 505 patients, nine had intracranial invasions
      (incidence rate, 1.8%). The mortality rate was high among these patients (44.4%,
      4/9). Among the various risk factors identified, diabetes had the greatest
      influence (66.7%, 6/9), which in combination with an immunocompromised condition
      and cirrhosis is indicative of a poor prognosis.

PMID- 28757714
TI  - Microfilaria in a thyroid nodule discovered by fine needle aspiration cytology.
AB  - Filariasis is a major health problem in tropical countries, including India. The
      disease is endemic all over India, especially in Uttar Pradesh, Andhra Pradesh,
      Orissa, Bihar, Jharkhand, Tamil Nadu, Kerala, and Gujarat. A heavy parasitic load
      may appear in the blood, urine with chyle, and at times in scrotal aspirates. It
      is very unusual to find microfilaria in thyroid aspirate. Here, we present a rare
      case in which microfilaria was found during fine needle aspiration cytology of a
      solitary thyroid nodule.

PMID- 28757715
TI  - Outbreak of multidrug-resistant tuberculosis in an aboriginal family in eastern
      Taiwan.
AB  - Spread of multidrug-resistant tuberculosis (MDR-TB) strains in the general
      population presents a serious threat to public health and severely threatens
      existing control efforts. Techniques such as spoligotyping and Mycobacterium
      interspersed repetitive units-variable-number tandem-repeat typing of
      mycobacterial isolates have been employed to confirm familial outbreaks of MDR
      TB. We diagnosed and traced four MDR-TB cases in a family via genotyping. Despite
      aggressive treatment, the index case remained culture positive, but the other
      patients were cured. This is the first documentation of a familial MDR-TB
      outbreak affecting human immunodeficiency virus-seronegative patients in eastern
      Taiwan. Molecular techniques are important in the identification of sources of
      MDR-TB infections. The adult index case in our study developed MDR-TB due to poor
      compliance with the drug regimen (acquired resistance), followed by transmission
      of MDR-TB to his children in close household contact. This emphasizes the
      importance of an effective drug delivery program, such as directly observed
      treatment, to improve drug compliance and prevent the emergence of drug-resistant
      cases.

PMID- 28757716
TI  - Cellular-type neurothekeoma over the chest wall of a woman.

PMID- 28757718
TI  - Emphysematous cholecystitis.

PMID- 28757717
TI  - Extraskeletal osteosarcoma in the back.

PMID- 28757719
TI  - Use of extracorporeal removal techniques in patients with paraquat toxicity and
      unknown hepatitis viral marker status.

PMID- 28757720
TI  - Validity and reliability of swallowing screening tools used by nurses for
      dysphagia: A systematic review.
AB  - Dysphagia following neurological impairment increases the risk of dehydration,
      malnutrition, aspiration pneumonia, and even death. Screening for dysphagia has
      been reported to change negative outcomes. This review evaluated the validity and
      reliability of measurement tools for screening dysphagia in patients with
      neurological disorders to identify a feasible tool that can be used by nurses.
      Electronic databases were searched for studies from 1992 to 2015 related to
      dysphagia screening measurements. The search was applied to the Pubmed, CINAHL,
      Cochrane, Medline, EBSCO host, and CEPS + CETD databases. A checklist was used to
      evaluate the psychometric quality. The tools were evaluated for their feasibility
      for incorporation into routine care by nurses in hospitals. A total of 104 papers
      were retrieved, and eight articles finally met the inclusion criteria. The
      sensitivity and specificity of the screening tools ranged from 29% to 100% and
      from 65% to 100%, respectively. The interrater reliability ranged from good to
      excellent agreement. On the basis of quality evaluations, all the included
      studies had a risk of bias because of inadequate methodological characteristics.
      The Standardized Swallowing Assessment is the most suitable tool for detecting
      dysphagia because its psychometric properties and feasibility are higher than
      those of other screening tools that can be administered by nurses.

PMID- 28757721
TI  - Prevalence of vancomycin resistant Staphylococcus aureus (VRSA) in methicillin
      resistant S. aureus (MRSA) strains isolated from burn wound infections.
AB  - OBJECTIVES: The increase in resistance of methicillin resistant Staphylococcus
      aureus (MRSA) strains to vancomycin has been perceived as a formidable threat in
      the therapeutic fields. The present study investigated the vancomycin resistance
      traits of MRSA isolates [vancomycin resistant S. aureus (VRSA)] collected from
      burn patients. MATERIALS AND METHODS: Twenty-nine of 40 isolates of
      Staphylococcus spp. were identified as S. aureus which were further tested
      against 20 commercially available antibiotics to determine antibiotic
      susceptibility patterns. RESULTS: Imipenem was the most potential antibiotic
      resulting in 90% sensitivity, followed by netilmicin, clindamycin, and
      nitrofurantoin (80% sensitivity). All isolates were found to be resistant to
      penicillin. Approximately 75% of them were found to be resistant to methicillin,
      oxacillin, azithromycin, cipro-floxacin, and tetracycline. Approximately 45%
      isolates exhibited resistance to amikacin, chloramphenicol, gentamycin, and
      tobramycin. Twenty-one of the 29 strains of S. aureus were MRSA, of which 11 were
      resistant to vancomycin when employing the disc diffusion method. However, when
      the broth micro-dilution procedure was used to measure the minimum inhibitory
      concentration (MIC) of vancomycin, eight isolates were resistant to vancomycin,
      six with an MIC of 32 MUg/mL and two with an MIC of 64 MUg/mL. CONCLUSION: A
      significant fraction of VRSA was found among MRSA strains in this study,
      revealing the necessity for new and effective drugs against MRSA.

PMID- 28757722
TI  - Estrogen and G protein-coupled estrogen receptor agonist G-1 cause relaxation of
      human gallbladder.
AB  - OBJECTIVE: Estrogen interacts with a membrane receptor, G protein-coupled
      estrogen receptor (GPER). It was reported that 17beta-estradiol was able to
      inhibit contraction of the human colon and cause relaxation of the guinea pig
      gallbladder, however, the involvement of GPER was not clarified. The aim of the
      present study was to investigate the effect of estrogen on human gallbladder
      motility and the possible role of GPER. MATERIALS AND METHODS: Relaxation of
      human gallbladder strips were measured using isometric transducers. Expression of
      GPER was evaluated by reverse transcription polymerase chain reaction (PCR),
      realtime PCR, and immunohistochemistry. RESULTS: In human gallbladder strips,
      17beta-estradiol and G-1 elicited marked and rapid relaxation, whereas tamoxifen
      produced mild concentration-dependent relaxation. The relative efficacies to
      cause relaxation were as follows: 17beta-estradiol = G-1 > tamoxifen. The
      relaxant response of 17beta-estradiol was not attenuated by tetrodotoxin or
      conotoxin GVIA. This implies that nerve stimulation was not involved in the
      17beta-estradiol-induced gallbladder relaxation. Analysis by reverse
      transcription PCR and real-time PCR showed that GPER was expressed in the human
      gallbladder. Further analysis by immunohisto-chemistry revealed that GPER was
      expressed in the gallbladder muscle. This suggests that 17beta-estradiol relaxes
      the human gallbladder via GPER. CONCLUSION: These results demonstrate for the
      first time that 17beta-estradiol and GPER agonist G-1 cause relaxation of the
      human gallbladder, probably through GPER. Estrogen might play an important role
      in the control of human gallbladder motility.

PMID- 28757723
TI  - Deduced probable HLA-C*07:359-associated human leukocyte antigen haplotypes found
      by case analysis of Taiwanese unrelated bone marrow hematopoietic stem cell
      donors.
AB  - OBJECTIVES: HLA-C*07:359 is a low-incidence allele in the human leukocyte antigen
      (HLA)-C locus. The objective of this study is to report the ethnicity and
      haplotypes of HLA-C*07:359 that were found during an analysis of Taiwanese
      unrelated bone marrow hematopoietic stem cell donors. MATERIALS AND METHODS: A
      sequence-based typing method was employed to confirm low-incidence al-leles.
      Polymerase chain reaction was performed to amplify exon 2 and exon 3 of the HLA
      A, HLA-B, and HLA-C loci, as well as exon 2 of the HLA-DRB1 locus, using group
      specific primer sets. The amplicons were sequenced in both directions using
      BigDye Terminator Cycle Sequencing Ready Reaction kits, according to the
      manufacturer's protocols. The potential unrelated bone marrow stem cell donors
      investigated here are individuals with Taiwanese ethnicity who are participating
      in the Tzu Chi Bone Marrow Donor Registry. RESULTS: The DNA sequence of C*07:359
      is identical to that of C*07:02:01:01 in exons 2, 3, and 4 except at residue 862,
      where the G of C*07:02:01:01 is substituted by the A of C*07:359. The nucleotide
      exchange leads to an amino acid replacement at codon 264, where the glutamic acid
      of C*07:02:01:01 is replaced by the lysine of C*07:359. We deduced a probable HLA
      B and HLA-C haplotype that is associated with C*07:359 in Taiwanese, namely B*39
      C*07:359. CONCLUSION: Information on the ethnicity of the C*07:359 allele and its
      deduced probable HLA haplotypes that are associated with the low-incidence
      C*07:359 allele reported here are of value to HLA testing laboratories for
      reference purposes. In addition, they can be used by stem cell transplantation
      donor search coordinators to determine a strategy for finding compatible donors
      using unrelated bone marrow donor registries when patients carry this uncommon
      HLA allele.

PMID- 28757724
TI  - Neurophysiological comparisons of subthalamic deep-brain stimulation for
      Parkinson's disease between patients receiving general and local anesthesia.
AB  - OBJECTIVES: Subthalamic nucleus deep-brain stimulation (STN-DBS) is suggested as
      a standard treatment for patients with Parkinson's disease (PD) and drug-related
      side effects. Most centers perform the operation under local anesthesia (LA) to
      ensure better microelectrode recording (MER). Given the advances in imaging and
      MER, general anesthesia (GA) is perceived as an alternative choice for PD
      patients undergoing STN-DBS. However, the outcomes in terms of clinical symptoms
      and MER after GA have rarely been reported. In this report, we compared the
      outcomes after STN-DBS for PD between patients receiving LA and GA. MATERIALS AND
      METHODS: We included 16 patients with comparable severity of PD undergoing either
      GA (n = 8) or LA (n = 8) for STN-DBS. MER was performed in all patients for STN
      localization, and surgical outcomes were evaluated using the Unified PD Rating
      Scales, and Mini-mental status examination. All adverse effects were documented.
      RESULTS: Both groups (GA and LA) acquired similar benefits from STN-DBS, and
      there were no significant differences in neuropsychiatric outcome analysis
      between groups. There were no significant differences in stimulation parameters
      and adverse effects from STN-DBS between groups. The GA group had a trend toward
      a lower frequency rate of STN firing on MER. CONCLUSION: Although the GA group
      has a lower neuronal firing frequency in the STN during surgery, STN-DBS under GA
      showed comparable and non-inferior outcomes as compared with STN-DBS under LA.

PMID- 28757725
TI  - Inverse relationship of bone mineral density and serum level of N-terminal pro-B
      type natriuretic peptide in peritoneal dialysis patients.
AB  - OBJECTIVE: Chronic kidney disease is associated with decreased bone mineral
      density (BMD). In this study, the relationship between BMD and the fasting serum
      concentration of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) was
      evaluated in peritoneal dialysis (PD) patients. MATERIAL AND METHODS: Fasting
      blood samples were obtained from 52 PD patients. BMD was measured by dual energy
      X-ray absorptiometry of the lumbar vertebrae (L2-L4). The serum NT-pro-BNP level
      was measured by an electrochemiluminescence immunoassay. RESULTS: Ten patients
      (19.2%) had osteoporosis, 23 patients (44.2%) had osteopenia, and 19 patients had
      normal BMD. Increased serum NT-pro-BNP (p < 0.001), advanced age (p = 0.012),
      decreased body mass index (p = 0.006), body height (p = 0.018), and body weight
      (p = 0.004) were associated with lower lumbar T-scores, but sex, menopausal
      status, PD modality, diabetes mellitus, and hypertension were not. Multivariate
      forward stepwise linear regression analysis with adjustment for age, body height,
      body weight, body mass index, and log-NT-pro-BNP indicated that a high serum
      level of log-NT-pro-BNP (R2 change = 0.346; p < 0.001) and low body weight (R2
      change = 0.208; p < 0.001) were significantly and independently associated with
      poor lumbar BMD. CONCLUSION: A high serum level of NT-pro-BNP and low body weight
      were associated with poor BMD in PD patients.

PMID- 28757726
TI  - A blood clot hanging in the anterior chamber due to delayed suprachoroidal
      hemorrhage after trabeculectomy.
AB  - Delayed suprachoroidal hemorrhage (DSCH) is a rare but devastating complication
      of trabeculectomy, usually resulting in a poor visual prognosis. The typical
      presentation of DSCH includes acute visual loss, high intraocular pressure, a
      shallow anterior chamber, and choroidal elevation. We report a patient with
      hypertension who had DSCH following trabeculectomy, with an unusual presenting
      picture of a large blood clot hanging in a deep anterior chamber. Anterior
      chamber irrigation and choroidal taps were performed immediately. The intraocular
      pressure was soon controlled, and the visual acuity returned to 20/25 in 6
      months.

PMID- 28757727
TI  - Neovascular glaucoma following Nd:YAG laser capsulotomy in a patient with
      diabetes and syphilitic uveitis.
AB  - A diabetic woman had been suffering from progressively blurry vision in the right
      eye for 1 year after cataract surgery. Slit lamp examination revealed bilateral
      band keratopathy with quiescent anteriorchamber reaction, an intumescent cataract
      in the left eye, and dense posterior capsular opacity in the right eye.
      Capsulotomy was performed, but this led to neovascular glaucoma. Because of a
      refractory elevation in intraocular pressure, trabeculectomy with mitomycin C
      treatment, vitrectomy with panretinal photocoagulation, and intravitreal
      injection of bevacizumab were performed. A positive rapid plasma reagin test and
      a positive Treponema pallidum hemagglutination assay led to the impression of
      syphilitic uveitis, and the patient was treated with intravenous penicillin for 2
      weeks. The visual acuity of the right eye was 0.1 at the 12th-month follow up.
      This case shows that neovascular glaucoma may present as a complication of
      capsulotomy in uveitic/diabetic eyes.

PMID- 28757728
TI  - Minimal deviation adenocarcinoma of the uterine cervix: A case report.
AB  - Minimal deviation adenocarcinoma (MDA) of the uterine cervix is a rare disease.
      The rate of misdiagnosis is relatively high and there is no standard treatment. A
      58-year-old woman presented with an abnormal Pap smear revealing atypical
      glandular cells and vaginal mucoid discharge. Cervical biopsy revealed cervicitis
      and an endometrium with atypical glands and increasing mitoses. A frozen section
      of curetted endometrial tissue revealed adenocarcinoma. Surgical staging with
      laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic
      lymph node dissection was then performed. However, uterine cervical MDA was
      confirmed by pathology and immunohistochemistry with carcinoembryonic antigen and
      vimentin. Because the staging surgery was inadequate (the parametrium was not
      radically resected), postoperative adjuvant therapy with concurrent
      chemoradiation was performed. The patient remained disease-free as of the last
      follow-up 6 months postoperatively. MDA is difficult to diagnose and depends on
      its clinical manifestations and pathologic features. Surgery with adjuvant
      chemoradiotherapy achieves good outcomes.

PMID- 28757729
TI  - Pathological findings of ketamine ureteritis.

PMID- 28757730
TI  - Granulosa cell tumor of the ovary.

PMID- 28757731
TI  - Invasive Klebsiella pneumoniae liver abscess syndrome.

PMID- 28757732
TI  - Botulinun A toxin urethral sphincter injection for neurogenic or nonneurogenic
      voiding dysfunction.
AB  - Voiding dysfunction due to detrusor underactivity or urethral sphincter
      dysfunction is a treatment challenge for urologists. Recently, urologists have
      used botulinum toxin A (BoNT-A) injection into the urethral sphincter to treat
      voiding dysfunction. This treatment has been found to decrease urethral pressure
      and postvoid residual volume, and increase voiding efficiency in patients with
      neurogenic detrusor sphincter dyssynergia, nonneurogenic dysfunctional voiding,
      and detrusor underactivity. Although not all patients can achieve excellent
      therapeutic outcomes, patients with idiopathic detrusor underactivity might have
      recovery of detrusor contractility after urethral sphincter BoNT-A injection.
      However, urinary incontinence might be a de novo adverse event after treatment.
      Repeat urethral injection is necessary to maintain therapeutic efficacy. Patients
      should be fully informed of the limited therapeutic efficacy and possible adverse
      events prior to treatment. This article reviews recent studies of urethral
      sphincter BoNT-A treatment for voiding dysfunction.

PMID- 28757733
TI  - Emergence of carbapenemase-producing urinary isolates at a tertiary care hospital
      in Dhaka, Bangladesh.
AB  - OBJECTIVES: A growing incidence of pathogens producing carbapenemases has been
      observed in many countries including Bangladesh. The present study was carried
      out to determine the presence of carbapenemase producers among uropathogens.
      MATERIALS AND METHODS: A total of 138 Gram-negative uropathogens were isolated
      and identified by conventional methods and were screened for carbapenemase
      production using imipenem discs. Phenotypic identification of carbapenemase
      production was done by the double disc synergy test, combined disc assay, and
      modified Hodge test. The minimum inhibitory concentration of imipenem was
      determined by the agar dilution method. Genes encoding blaNDM-1, blaIMP, blaVIM,
      blaKPC and blaOXA-48/blaOXA-181 were identified by polymerase chain reaction.
      RESULTS: Twenty (14.49%) imipenem resistant strains were detected among 138 Gram
      negative uro-pathogens. The most common isolates were Escherichia coli and
      Klebsiella spp. Among 20 imipenem resistant strains, 16 (80%) carbapenemase
      producers were detected by polymerase chain reaction, 13 (65%) by double disc
      synergy, 15 (75%) by combined disc assay, and seven (35%) by modified Hodge test.
      The blaNDM-1 gene was most prevalent (55%), followed by blaOXA-48/OXA-181, blaKPC
      (20%), blaVIM (15%), and blaIMP (10%). More than one carbapenemase gene was
      present in nine (45%) of the isolates. The minimum inhibitory concentration of
      imipenem of the carbapenemase producers ranged from >=128 MUg/mL to 4 MUg/mL.
      Overall, carbapenemase encoding genes were detected in 11.6% (16/138) of the
      studied Gram-negative uropathogens. All (100%) of the carbapenemase-producing
      organisms were resistant to all tested antibiotics apart from colistin.
      CONCLUSION: The study shows a significant rate of urinary isolates were
      carbapenemase producers, including a high prevalence of blaNDM-1, in Bangladesh.

PMID- 28757734
TI  - Deduced probable HLA haplotypes associated with HLA-C*04:82 found by case
      analysis of Taiwanese individuals.
AB  - OBJECTIVE: HLA-C*04:82 is a low incidence HLA-C allele. The aim here is to report
      the ethnicity of C*04:82 and its associated HLA haplotypes among Taiwanese
      individuals. MATERIALS AND METHODS: A sequence-based typing method was used to
      confirm this low incidence allele. Polymerase chain reaction was performed to
      amplify exons 2 and 3 of the HLA-A, HLA-B, and HLA-C loci and exon 2 of the HLA
      DRB1 locus using group-specific primer sets. The amplicons were sequenced in both
      directions using Terminator Cycle Sequencing Ready Reaction kits and the
      manufacturer's protocols. The potential unrelated bone marrow stem cell donors in
      this study were randomized individuals with Taiwanese ethnicity who participated
      in the Tzu Chi Bone Marrow Donor Registry. The family members in the family part
      of the study were volunteer blood donors. RESULTS: The DNA sequence of C*04:82
      was identical to C*04:01:01:01 in exons 2, 3, and 4. It differed from
      C*04:01:01:01 in exon 5 where a segment of nucleotides (CTAGCTGTC) was inserted
      between residues 969 and 970 of C*04:01:01:01. The insertion of these nucleotides
      caused a 35 amino acid alteration to the protein sequence of C*04:01:01:01. Three
      probable HLA haplotypes that were associated with C*04:82 among Taiwanese
      individuals were deduced. Confirmation of the DNA and protein sequences of
      C*04:82 and its Taiwanese ethnicity were established in this study. CONCLUSION:
      The ethnicity of the C*04:82 allele and the deduced probable HLA haplotypes
      associated with the low-incidence C*04:82 allele are of value for reference
      purposes for HLA testing laboratories. In addition, they can be used by search
      coordinators to aid the creation of a strategy for finding compatible stem cell
      donors for patients who carry this uncommon HLA allele.

PMID- 28757735
TI  - Effects of caffeine on cell viability and activity of histone deacetylase 1 and
      histone acetyltransferase in glioma cells.
AB  - OBJECTIVE: The prognosis of patients with glioblastoma remains poor even after
      various treatments such as surgery, radiotherapy, and chemotherapy. Thus,
      development of new drugs is urgently needed. The mechanisms underlying the
      cytotoxicity of caffeine in glioma cells are not clearly understood. This study
      aimed to assess the activities of histone deacetylase 1 (HDAC1) and histone
      acetyltransferase (p300) in RT2 glioma cells treated with caffeine. MATERIALS AND
      METHODS: Cell viability and activity of HDAC1 and p300 in RT2 glioma cells were
      assayed after treatment with caffeine for 48 hours. RESULTS: Cell viability
      decreased significantly after treatment with 0.5mM, 1mM, and 2mM caffeine. HDAC1
      protein activity decreased significantly with various concentrations of caffeine,
      whereas the activity of p300 increased significantly. In addition, the viability
      of RT2 cells remained high, but HDAC1 activity decreased, and p300 activity
      increased markedly with 0.5mM caffeine treatment. We used microRNA and small
      interfering RNA (siRNA) to regulate HDAC1 and p300 to further understand the
      impact on glioblastomas. siRNA downregulated p300 and thus increased the
      viability of RT2 cells, therefore, caffeine combined with siRNA abolished the
      efficacy of caffeine, which confirmed that caffeine upregulated p300 and reduced
      cell viability. We also found increased HDAC1 activity when RT2 cells were
      treated with a combination of caffeine and miR-449a and thus increased the
      viability of RT2 cells. CONCLUSION: Our data suggest that a new strategy,
      caffeine, could increase glioma cell death by decreasing HDAC1 activity and/or by
      increasing p300 activity. The changes in HDAC1 and p300 activities appeared to
      occur earlier than loss of RT2 cells.

PMID- 28757736
TI  - Comparison between the Trachway video intubating stylet and Macintosh
      laryngoscope in four simulated difficult tracheal intubations: A manikin study.
AB  - OBJECTIVES: It remains to be determined whether the TVI-4000 Trachway video
      intubating (TVI) stylet (Markstein Sichtec Medical Corp, Taichung, Taiwan), an
      airway device for novices, improves airway management practice by experienced
      anesthesiologists. The aim of this study was to evaluate the feasibility of using
      the TVI stylet in difficult tracheal intubation situations compared with that of
      using the Macintosh laryngoscope on an airway manikin. MATERIALS AND METHODS: Ten
      anesthesiologists (with 3-21 years' experience), including three senior
      residents, participated. We compared tracheal intubation in four airway
      scenarios: normal airway, tongue edema, cervical spine immobilization, and tongue
      edema combined with cervical spine immobilization. The time of tracheal
      intubation (TTI), success rate, and perceived difficulty of intubation for each
      scenario were compared and analyzed. RESULTS: The TTI was significantly shorter
      in both the tongue edema and combined scenarios with the TVI stylet compared with
      the Macintosh laryngoscope (21.60 +/- 1.45 seconds vs. 24.07 +/- 1.58 seconds and
      23.73 +/- 2.05 seconds vs. 26.6 +/- 2.77 seconds, respectively). Success rates
      for both devices were 100%. Concomitantly, participants rated using the TVI
      stylet in these two scenarios as being less difficult. CONCLUSION: The learning
      time for tracheal intubation using the TVI stylet in difficult airway scenarios
      was short. Use of the TVI stylet was easier and required a shorter TTI for
      tracheal intubation in the tongue edema and combined scenarios.

PMID- 28757737
TI  - Conceptualizing workplace based assessment in Singapore: Undergraduate Mini
      Clinical Evaluation Exercise experiences of students and teachers.
AB  - OBJECTIVES: The Mini-Clinical Evaluation Exercise (mini-CEX) is one of the most
      commonly used clinical assessment tools to provide learner feedback to drive
      learning. High quality constructive feedback promotes development and improves
      clinical competency. However, the effectiveness of feedback has not been
      objectively evaluated from the learners' and assessors' points of view,
      especially in Asia, where the nature of the student-tutor relationship is
      relatively hierarchical. This study seeks to compare the strengths, limitations,
      and feedback of the mini-CEX between assessors and students. MATERIALS AND
      METHODS: A cross-sectional study was conducted among 275 senior medical
      undergraduates at the National University of Singapore and 121 clinical tutors
      from seven restructured hospitals in Singapore. Data was collected via a self
      administered questionnaire. Univariate analysis was used to determine the
      prevalence of responses, as well as differences between tutors and students.
      RESULTS: The mini-CEX provided immediate feedback and timely correction of
      mistakes. However, effective administration was limited by inter-tutor
      variability and lack of time. Students reported being receptive to feedback, but
      tutors disagreed and felt that students were resistant to negative feedback.
      Additionally, students felt that their performance was compared unfairly against
      more senior students, although the tutors felt otherwise. CONCLUSION: The mini
      CEX is an effective assessment tool, but is limited by barriers to administration
      and evaluation. Differing opinions and expectations between tutors and students
      could provide an interesting focal point for future studies.

PMID- 28757738
TI  - Insidious malignant triton tumor of the chest wall with late flare-up.
AB  - Malignant triton tumor is a rare malignant peripheral nerve sheath tumor with
      rhabdomyoblastic differentiation. Most of these tumors are located in the head,
      neck, and extremities, and about half of cases are associated with
      neurofibromatosis type 1 featuring cafe-au-lait spots or cutaneous neurofibromas.
      We present a 76-year-old man with an insidious chest wall tumor with late
      progressive painful enlargement and pleural and pulmonary involvement. Complete
      resection of the affected thoracic wall as well as single separate lesions in the
      parietal pleura and left upper lung was carried out. The pathological examination
      confirmed that it was a malignant triton tumor. The patient received adjuvant
      chemo-radiotherapy but eventually succumbed to disease relapse and distant
      metastases 6 months after the surgery.

PMID- 28757739
TI  - Side-branch wire entrapment: Early recognition and management.
AB  - Side-branch wire (SBW) entrapment has been reported with increasing frequency
      recently. We report early recognition of SBW entrapment in a 60-year-old woman.

PMID- 28757740
TI  - Isolated complete dislocation of the tarsal navicular without fracture: A rare
      injury.
AB  - Injuries to the midtarsal joints usually occur in various combinations such as
      fracture, fracture subluxation, and fracture dislocation. Isolated dislocations
      of the navicular bone without fracture are rare injuries. The few existing case
      reports describe the probable mechanism of injury and optimal treatment. We
      present a 64-year-old diabetic man whose tarsal navicular was completely
      dislocated without fracture following a traffic accident. The most probable
      mechanism of injury was an abduction-pronation injury causing a midtarsal
      dislocation, and on spontaneous reduction, the navicular was dislocated medially.
      This mechanism is similar to perilunate dislocation. Computed tomography of the
      involved foot was done to accurately define the full extent of the bony injury
      and magnetic resonance imaging was required to determine if there was a
      ligamentous injury and to assess the attachment of soft tissues to the displaced
      bone to help assess the risk of avascular necrosis. The patient was treated
      successfully with open reduction and primary talonavicular arthrodesis with
      Kirschner wires.

PMID- 28757741
TI  - Solitary adrenal tuberculosis.

PMID- 28757742
TI  - Wegener's granulomatosis that mimics nasopharyngeal cancer.

PMID- 28757743
TI  - Appendicular foreign body presenting with appendicular mass.

PMID- 28757744
TI  - HLA haplotype in association with the low incidence C*07:66 allele found by case
      analysis of Taiwanese and mainland Chinese individuals.
AB  - OBJECTIVES: HLA-C*07:66 is a low-incidence HLA-C allele. The aim of the study is
      to report the Taiwanese and mainland Chinese ethnicities of individuals with
      C*07:66, together with its uniqueness and polymorphism. MATERIALS AND METHODS: A
      sequence-based typing method was employed to confirm this low-incidence allele.
      Polymerase chain reaction was performed to amplify exons 2, 3, and 4 of the HLA
      A, HLA-B, and HLA-C loci and exon 2 of the HLA-DRB1 and HLA-DQB1 loci using group
      specific primer sets. The amplicons were sequenced in both directions using
      BigDye Terminator Cycle Sequencing Ready Reaction kit. The blood donors in this
      study consisted of randomized Taiwanese and mainland Chinese individuals and
      family members with the C*07:66 allele. RESULTS: The DNA sequence of C*07:66 is
      identical to that of C*07:02:01:01 for exons 2, 3, and 4, except for residue 688
      in exon 4. This nucleotide substitution causes a single amino acid alteration to
      the protein sequence of C*07:02:01:01. Confirmation of the DNA and protein
      sequences of C*07:66 and the Taiwanese and mainland Chinese ethnicities of
      individuals with this allele were established in this study. One probable HLA
      C*07:66-associated HLA haplotype may be deduced from these individuals.
      CONCLUSION: The information on the ethnicity of the C*07:66 allele and the
      deduced probable HLA haplotype associated with the low-incidence C*07:66 allele
      reported in this study may aid in HLA testing laboratories for reference
      purposes. In addition, they can be used by stem cell transplant donor search
      coordinators to help create, for patients bearing this uncommon HLA allele,
      strategies for finding compatible donors using bone marrow donor registries
      comprising unrelated individuals.

PMID- 28757745
TI  - Role of micronutrients in congestive heart failure: A systematic review of
      randomized controlled trials.
AB  - OBJECTIVES: To assess the effect of micronutrients on health outcomes in patients
      with heart failure. MATERIALS AND METHODS: Only randomized controlled trials
      testing the effectiveness of different micronutrients either singly or combined
      versus placebo in heart failure patients were included. We conducted a search in
      different databases such as Medline from PubMed, Embase and Scopus from Elsevier,
      and Google Scholar. The keywords used in the search were "Heart Failure" and its
      cognates, "Micronutrient," "Minerals," and names of individual micronutrients.
      RESULTS: Out of 3288 titles and abstracts reviewed, only 11 trials comprising 529
      individuals were found to be appropriate to be included in the final review. It
      was found that micronutrients, either single or combined, improved the health
      outcomes of heart failure patients by improving exercise tolerance, functional
      capacity, left ventricular function, flow-dependent dilation, and inflammatory
      milieu, thereby improving the quality of life of health failure patients. Certain
      micronutrients also normalized endothelial dysfunction. CONCLUSION: Overall, this
      systematic review found sufficient evidence to support a large-scale trial on
      micronutrient supplementation in patients with heart failure.

PMID- 28757746
TI  - Characteristics and outcomes of patients with emergency department revisits
      within 72 hours and subsequent admission to the intensive care unit.
AB  - OBJECTIVE: This study aimed to investigate the characteristics and outcomes of
      patients with emergency department (ED) revisits within 72 hours and subsequent
      admission to the intensive care unit (ICU). MATERIALS AND METHODS: The medical
      records of all adult patients revisiting the ED of a single tertiary referral
      medical center with ICU admissions between January 2012 and September 2014 were
      reviewed in terms of patient characteristics, clinical manifestations, diagnoses,
      triage according to the Taiwan Triage and Acuity Scale, causes of revisits, and
      mortality. RESULTS: The majority of the 51 patients reviewed were male (64.7%).
      Their mean age was 62.9 +/- 14.9 years. Most patients visited the ED during the
      evening shift (51%) and were categorized into triage Level III (76.5%) during
      their first ED visit. The causes of revisits were doctor-related (21/51, 41.1%),
      illness-related (18/51, 35.3%), and patient-related (12/51, 23.5%). Disease
      categories included the neurological (23.5%), digestive (23.5%), and
      cardiovascular systems (21.6%). Abdominal pain and vertigo/dizziness were the two
      most common initial manifestations. The mortality rate was 27.5%. Malignancy and
      hepatic diseases were the two most common underlying medical conditions for
      nonsurvivors. In addition, patients initially presenting to the ED with lower
      triage scores (III & IV) had a higher mortality rate than those with higher
      scores (I & II). CONCLUSION: Most of the patients who revisited the ED within 72
      hours and were subsequently admitted to the ICU visited the ED during the evening
      shift and were categorized into triage Level III on their first visit. The most
      common chief complaint at the first visit was abdominal pain. The most common
      cause of revisits with ICU admission was doctor-related, while the most common
      underlying disease was hypertension. Significantly higher mortality was observed
      after ED revisits in patients with lower triage scores with underlying malignancy
      and liver cirrhosis.

PMID- 28757747
TI  - Guillain-Barre syndrome complicating dengue fever: Two case reports.
AB  - Guillain-Barre syndrome is a rare neurological manifestation associated with
      dengue infection. More common antecedent infections include Campylobacter jejuni
      and Cytomegalovirus infection. Here, we report two cases of Guillain-Barre
      syndrome complicating dengue infection.

PMID- 28757748
TI  - Postoperative herpetic endophthalmitis-A case report.
AB  - We report a case of herpetic endophthalmitis following cataract surgery. A 65
      year-old man underwent uneventful phacoemulsification and vision improved within
      the first few postoperative days. However, visual loss with an anterior chamber
      reaction of ++++ and a ++ vitreous cell were noted in the 4th postoperative week.
      Repeated intravitreal injection of vancomycin and ceftriaxone, pars plana
      vitrectomy and removal of the intraocular lens (IOL), and the capsular bag were
      performed sequentially but in vain. Bacterial, mycobacterial, and fungal culture
      of the IOL and capsular bag demonstrated negative findings. Pathological
      examination revealed no pathogen but a number of mononuclear cells and several
      multinuclear giant cells. Serology exam revealed positive herpes simplex virus
      immunoglobulin (Ig)M and IgG. The intraocular inflammation resolved soon after
      changing antibiotics to oral valcyclovir.

PMID- 28757749
TI  - Successful treatment of a newborn with congenital hyperinsulinism having a novel
      heterozygous mutation in the ABCC8 gene using subtotal pancreatectomy.
AB  - Congenital hyperinsulinism (CHI) is the most common cause of persistent
      hypoglycemia in newborns and infants. CHI is characterized by unregulated
      secretion of insulin from pancreatic beta: cells. Here, we reported the case of a
      large-for-gestational-age, full-term newborn that suffered from CHI and developed
      severe and persistent hypoglycemia at an early stage of life. The infant was
      nearly unresponsive to medical treatment, which included continuous intravenous
      glucagon infusion, oral diazoxide, and nifedipine. After medical treatment had
      failed, an 18-fluoro L-3,4-dihydroxyphenylalanine positron emission tomography
      scan of the patient showed a focal lesion at the neck of the pancreas. The
      patient received subtotal pancreatectomy, and shortly after the procedure, the
      patient's blood sugar returned to the normal range. The patient was confirmed to
      have a novel heterozygous mutation at position c.2475+1G>A of the ABCC8 gene.
      This is the first report of a focal form of CHI in a patient in Taiwan, which had
      preoperatively been confirmed using 18-fluoro L-3,4-dihydroxyphenylalanine
      positron emission tomography.

PMID- 28757751
TI  - An unusual echocardiographic presentation of left atrial dissection following
      cardiopulmonary cerebral resuscitation.
AB  - Left atrial dissection (LatD) is a relatively rare perioperative complication
      during mitral valve repair. Here, we report a 64-year-old man who developed LatD
      after cardiopulmonary resuscitation was needed due to an extensive myocardial
      infarction. Aggressive cardiac massage resulted in cardiac rupture and massive
      bloody pleura effusion. Intraoperative three-dimensional transesophageal
      echocardiography revealed posterior-medial papillary muscle ruptured and
      separation of the endocardium from the left atrial myocardium. We speculate that
      this is the first report in the literature of LatD after cardiopulmonary cerebral
      resuscitation.

PMID- 28757750
TI  - Dialysis catheter-related pulmonary embolism in a patient with paraquat
      intoxication.
AB  - A 30-year-old woman was sent to the emergency room after alcohol and paraquat
      ingestion. After three sessions of hemoperfusion via the indwelling double-lumen
      catheter, the patient could tolerate ambient air and her urine output was good.
      However, on the 10th day of hospitalization, she had a sudden onset of dyspnea
      and hypoxia. Pulmonary embolism was diagnosed by a computed tomography pulmonary
      angiogram. The patient recovered after anticoagulation therapy. We could find no
      reports of dyspnea caused by pulmonary embolism in patients with paraquat
      intoxication. Here, we present this rare case; the indwelling double-lumen
      catheter might have been a cause of the pulmonary embolism.

PMID- 28757752
TI  - Adolescent onset of vertically transmitted untreated AIDS: A report of one case.
AB  - A 12-year-old adolescent girl with intractable pneumonia and desaturation was
      sent to our hospital. An immunocompromised state was highly suspected because of
      an oral thrush persisting for a year and pneumonia of unusual severity.
      Laboratory tests confirmed she had human immunodeficiency virus (HIV) infection
      and full-blown AIDS. She lived with her adopted parents and reported no history
      of sexual abuse, drug abuse, or blood transfusion. We contacted the Center of
      Disease Control and discovered that her mother had HIV and had passed away a few
      years ago, thus confirming that she was a case of vertically transmitted HIV
      patient who had only developed AIDS recently. Even though her mother had HIV, our
      public health department failed to follow her as a potential HIV victim, probably
      because routine HIV examinations for pregnant women only started in 2005, 4 years
      after she was born.

PMID- 28757753
TI  - Prenatal diagnosis of the maternal derivative chromosome der(15)t(Y;15)(q12;p13)
      in a dizygotic twin pregnancy.
AB  - Sex chromosome translocations are unique and must be considered separately from
      translocations between autosomes. Here, we describe the first prenatal case of
      one twin fetus with an unbalanced translocation between chromosome Y and
      chromosome 15, presenting a 46,XY,der(15)t(Y;15) karyotype. The other twin had a
      normal 46,XY karyotype. Cytogenetic analysis of the parental chromosomes revealed
      that the father had a normal 46,XY karyotype, whereas the mother exhibited a
      46,XX,der(15) t(Y;15) karyotype. Thus, the proband inherited this translocation
      from the mother. Fluorescence in situ hybridization analyses demonstrated that
      the breakpoint on chromosome Y involved a heterochromatin region (Yq12), while
      that on chromosome 15 involved a p-arm region (15p13). At 37 gestational weeks,
      healthy twins were delivered vaginally. We conclude that accurate identification
      of der(15) chromosomal content can facilitate not only prenatal diagnosis of a
      chromosomal aberration in one twin, but also prediction of the fetal phenotype.

PMID- 28757754
TI  - Therapeutic hypothermia brings favorable neurologic outcomes in children with
      near drowning.
AB  - A 1-year-10-month-old boy was admitted to our pediatric intensive care unit due
      to near drowning with pulmonary edema. A conventional ventilator with 100% oxygen
      supplementation was used initially, but was shifted to high frequency oscillatory
      ventilation as his oxygen saturation was around 84-88%. Therapeutic hypothermia
      was applied due to hypoxic ischemic encephalopathy with severe acidosis. His
      respiratory condition improved and he was extubated successfully on the 6th
      hospital day. The patient had no obvious neurological defects and he was
      discharged in a stable condition after 17 days of hospitalization. Our case
      report demonstrates the advantages of therapeutic hypothermia on survival and
      neurological outcomes in treating pediatric near drowning patients.

PMID- 28757755
TI  - Eosinophil-rich granuloma of the liver.

PMID- 28757756
TI  - Current consensus and controversy on the treatment of male lower urinary tract
      symptoms/benign prostatic hyperplasia.
AB  - Lower urinary tract symptoms (LUTS) are highly prevalent in men and increase with
      age. Because LUTS are common among elderly men, they are usually considered
      synonymous with benign prostatic hyperplasia (BPH). Drugs should be the first
      line treatment for BPH and surgical intervention should be performed only when
      there are complications or LUTS refractory to medical treatment. In addition to
      medical treatment, several minimally invasive therapies, such as thermal therapy,
      prostatic lift, laser evaporation, or laser enucleation techniques have been
      developed. Recent investigations have also revealed that bladder dysfunction such
      as detrusor overactivity and detrusor underactivity may also contribute to male
      LUTS. In the treatment of LUTS suggestive of BPH (LUTS/BPH), the following
      questions should be considered: Is there an obstruction? Are we treating BPH or
      LUTS? Can management targeting BPH reduce LUTS? Should patients with LUTS be
      treated before bladder outlet obstruction is confirmed? What is the role of
      transurethral resection of the prostate (TURP) nowadays? Will new techniques
      provide better outcomes than TURP? This article discusses the current consensus
      and controversies in the treatment of LUTS/BPH.

PMID- 28757758
TI  - Deduced probable human leukocyte antigen haplotypes associated with human
      leukocyte antigen DRB1*04:36 identified by case analysis of Taiwanese
      individuals.
AB  - OBJECTIVE: Human leukocyte antigen (HLA) DRB1*04:36 is a low-frequency HLA-DRB1
      allele. The aim here is to report the ethnicity of DRB1*04:36 and its associated
      HLA haplotypes among Taiwanese individuals. MATERIALS AND METHODS: A sequence
      based typing method was employed to confirm this low incidence allele. Polymerase
      chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci
      and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons
      were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready
      Reaction kits and the manufacturer's protocols. One group of unrelated blood
      donors used in this study consists of randomized individuals with Taiwanese
      ethnicity who participate in the Tzu Chi Bone Marrow Donor Registry and the other
      group are randomized unrelated individuals from mainland China. The family
      members in the family part of the study are volunteer blood donors. RESULTS: In
      exon 2, the DNA sequence of DRB1*04:36 is identical to DRB1*04:03:01 except for a
      nucleotide segment from residue 286 to residue 308. The nucleotide segment from
      residue 286 to residue 308, incidentally, is identical to that of
      DRB1*11:01:01:01. These observations suggest that DRB1*04:36 may have been
      derived through a gene recombination event involving DRB1*04:03:01 and
      DRB1*11:01:01:01. Our family study indicated that the HLA haplotype in
      association with DRB1*04:36 can be deduced to be A*24:02-B*39:01-DRB1*04:36. A
      randomized population study using Taiwanese suggests that additional DRB1*04:36
      associated HLA haplotypes seem to exist. CONCLUSION: The information on the
      ethnicity of the DRB1**04:36 allele, and the deduced probable HLA haplotypes
      associated with the low incidence DRB1*04:36 allele that we report here, is of
      value to HLA testing laboratories for reference purposes. In addition, they can
      be used by stem cell transplantation donor search coordinators to aid the
      creation of strategy for finding compatible donors who are part of unrelated bone
      marrow donor registries when a patient carries this uncommon HLA allele.

PMID- 28757757
TI  - Current consensus and controversy on the diagnosis of male lower urinary tract
      symptoms/benign prostatic hyperplasia.
AB  - Traditionally, male lower urinary tract symptoms (LUTS) have been considered a
      synonym for benign prostate hyperplasia (BPH) because most male LUTS develops in
      aging men. Medical treatment should be the first-line treatment for BPH and
      surgical intervention should be performed when there are complications or LUTS
      refractory to medical treatment. Recent investigations have revealed that bladder
      dysfunction and bladder outlet dysfunction contribute equally to male LUTS. In
      the diagnosis of LUTS suggestive of BPH (LUTS/BPH), the following questions
      should be considered: Is there an obstruction? Are the LUTS caused by an enlarged
      prostate? What are the appropriate tools to diagnose an obstructive BPH? Should
      patients with LUTS be treated before bladder outlet obstruction is confirmed?
      This article discusses the current consensus and controversies in the diagnosis
      of LUTS/BPH.

PMID- 28757759
TI  - Treating intracranial dural arteriovenous fistulas with gamma knife radiosurgery:
      A single-center experience.
AB  - OBJECTIVE: We evaluated the effectiveness and safety of gamma knife radiosurgery
      (GKRS) for the treatment of intracranial dural arteriovenous fistulas (dural
      AVFs) over the past 10 years. MATERIALS AND METHODS: The records of 21 patients
      diagnosed with dural AVFs between 2004 and 2014 and treated with GKRS were
      reviewed retrospectively. Complete obliteration (CO) was defined as total symptom
      relief plus confirmation through magnetic resonance imaging or conventional
      angiography. RESULTS: The median follow-up was 70.5 months (range 3-136 months).
      Five patients underwent embolization (2 after GKRS). One patient underwent GKRS
      twice. The CO rate was 47%, and partial to CO rate was 88%. The complete symptom
      resolution rate was 77%, and all patients achieved partial to complete symptom
      resolution. The CO rates for Borden Type I and Type II/III dural AVFs were 66.7%
      and 25% (P = 0.153), respectively, and complete symptom-free rates were 76.9% and
      75.0% (P = 1.000%), respectively. The median duration between initial GKRS and
      complete symptom resolution was 14.3 months. The median treatment to image-free
      durations for Borden Type I and Type II/III dural AVFs were 25.9 and 60.4 months
      (P = 0.028), respectively, and treatment to symptom-free durations were 10.6 and
      36.7 months (P = 0.103), respectively. One patient had a recurrent hemorrhage.
      Two patients experienced brain edema after stereotactic radiosurgery and one
      patient experienced cystic formation after GKRS. The morbidity rate was 19% (four
      patients) and there was no mortality. CONCLUSION: Treatment with GKRS for dural
      AVFs offers a favorable rate of obliteration. Patients with dural AVFs that are
      refractory or not amenable to endovascular or surgical therapy may be safely and
      effectively treated using GKRS.

PMID- 28757760
TI  - Comparison of Apgar scores in breech presentations between vaginal and cesarean
      delivery.
AB  - OBJECTIVE: The mode of delivery in breech presentation (BP) is controversial.
      Several studies have reported the advantages and disadvantages of delivery mode
      in BP. The aim of this study was to compare the Apgar scores in BPs between
      vaginal and cesarean delivery. MATERIALS AND METHODS: A retrospective study was
      conducted at Dr. Zainoel Abidin General Hospital from January 2010 to December
      2012. Data on the mode of delivery and Apgar scores at 1 and 5 min for infants
      with a BP were extracted from the medical records. Logistic regression was
      employed to assess the correlation between mode of delivery and Apgar scores. In
      addition, a meta-analysis was conducted to summarize findings from other regions.
      RESULTS: A total of 205 (3.9%) BPs among 5252 deliveries between January 2010 and
      December 2012 were analyzed for this study. There were 26% (52 cases) vaginal and
      74% (153 cases) cesarean deliveries. The mode of delivery for BP had a
      significant association with Apgar score at 1 min (odds ratio [OR] 95% confidence
      interval [CI] = 6.462 [2.476-16.870], P = 0.0001) and 5 min (OR 95% CI = 7.727
      [1.416-42.175], P = 0.018). Our meta-analysis showed that the delivery mode had a
      significant association with Apgar score in BP (OR: 3.69; 95% CI: 2.18-6.26, P =
      0.0001). CONCLUSIONS: There was a significant association between Apgar scores in
      BPs and mode of delivery. Our results suggest better outcomes for cesarean than
      vaginal delivery in BPs.

PMID- 28757761
TI  - A survey of the perception of well-being among emergency physicians in Taiwan.
AB  - OBJECTIVES: The objective of this study is to investigate the feelings (well
      being) of emergency physicians in Taiwan regarding their job and the relationship
      between these feelings and the work environment. MATERIALS AND METHODS: A
      questionnaire was used to survey emergency physicians across Taiwan from January
      to June 2014. The questionnaire contents were categorized into five specific
      factors that could affect well-being, including "emergency quality, emergency
      safety, support environment, workload, and salary and benefits." Well-being was
      rated directly on a scale of 1-10, with 10 indicating the highest level of
      happiness. Physician retention was also surveyed. The correlations among the five
      factors, well-being, and physician retention were analyzed. The five factors were
      quantified as a "happiness index" and compared between religious and nonreligious
      hospitals and medical centers and regional hospitals. RESULTS: A total of 398
      questionnaires were received, and the response rate was 39%. Of these, 42.7% of
      responders reported high ratings for well-being (scores of 7-10, 1 is the worse,
      and 10 is the best) and 40.3% felt neutral (scores of 5-6). Only 12.3% doctors
      did not think they would stay at the same position for the next 3 years. All five
      factors had moderately significant correlations with each other (gamma = 0.195
      0.534, P < 0.01). All five factors also significantly correlated with well-being.
      Emergency safety (gamma = 0.121, P < 0.05), salary and benefits (gamma = 0.143, P
      < 0.05), and well-being (gamma = 0.189, P < 0.01) were correlated with physician
      retention. The happiness indices of emergency quality, support environment, and
      workload were significantly higher in regional hospitals than medical centers.
      CONCLUSIONS: All five indicators had impacts on well-being. The respondents
      reported heavy workloads, including high stress and even poorly met physiological
      needs. In addition, the threat of violence, salaries, and well-being correlated
      with physician retention. Hospital administrators can make efforts to improve the
      well-being of doctors and physician retention by adjusting environmental factors.

PMID- 28757762
TI  - Tension wiring to increase stability of conventional plating for proximal humeral
      fractures: An alternative to a locking plate.
AB  - Fixation of comminuted or osteoporotic fractures in the proximal humerus is a
      challenge for orthopedic surgeons. In the past two decades, locking plates have
      been used for proximal humeral fracture fixation. However, complications such as
      loss of reduction have been reported, and the implants are not always available
      in some regions. Therefore, we describe an alternative procedure involving
      fixation with a nonlocking cloverleaf plate augmented with tension wiring to
      provide adequate stability and prevent loss of reduction.

PMID- 28757763
TI  - Immune reconstitution inflammatory syndrome-associated disseminated Kaposi's
      sarcoma in a patient infected with human immunodeficiency virus: Report of an
      autopsy case.
AB  - Immune reconstitution inflammatory syndrome is a collection of inflammatory
      disorders associated with paradoxical worsening of preexisting infectious
      processes following the initiation of highly active antiretroviral therapy
      (HAART) in individuals infected with human immunodeficiency virus (HIV). It
      involves a wide range of pathogens, neoplasms such as Kaposi's sarcoma (KS) and
      some autoimmune diseases. We describe an autopsy report of a 40-year-old man
      infected with HIV. He experienced a rapid dissemination of KS resulting in death
      within 6 months after starting HAART. His serum viral load had significantly
      decreased 4 log10 within 32 days and his CD4+ T-cell count increased 4-fold. He
      presented with multiple skin lesions over the chin and anterior neck, which
      rapidly spread over the trunk, 4 extremities, perianal region, and penis.
      Finally, he developed acute dyspnea and a plain chest radiograph showed bilateral
      pulmonary infiltrations. Despite treatment, he died of acute respiratory failure.
      At autopsy, multiple KS lesions were noted in the bilateral lungs, liver,
      kidneys, and gastrointestinal tract. Increased inflammatory cytokines during
      immune reconstruction from HAART-reactive human herpes virus type-8 infection,
      linked to the tumorigenesis of KS, finally led to rapid dissemination and death.

PMID- 28757764
TI  - Atypical presentation of bladder pheochromocytoma.
AB  - Bladder pheochromocytoma is a rare tumor. The typical manifestations are
      hematuria, hypertension, headache, sweating, and tachycardia provoked by
      micturition or overdistention of the bladder. We herein report a case of bladder
      pheochromocytoma in a 52-year-old woman who presented without micturition
      attacks. Her clinical course had a latent period of 10 years. A urinary bladder
      tumor was found incidentally on magnetic resonance imaging. Cystoscopy revealed a
      large submucosal tumor covered by congested urothelium with a broad base over the
      left lateral wall of the bladder. Transurethral resection was performed, and the
      final diagnosis was confirmed by pathological analysis. The patient remained
      recurrence free after 7-year follow-up.

PMID- 28757765
TI  - Pulseless electrical activity in acute massive pulmonary embolism during
      thrombolytic therapy.
AB  - We report a case of acute pulmonary embolism with hemodynamic instability
      diagnosed by a computed tomography pulmonary angiogram. The patient developed
      pulseless electrical activity during systemic thrombolytic therapy with
      recombinant tissue plasminogen activator. Successful return of spontaneous
      circulation was achieved after immediate cardiopulmonary resuscitation with chest
      compressions for 6 min. His electrocardiogram (ECG) on arrival in the emergency
      department displayed sinus tachycardia, an S wave in lead I, a Q wave in lead
      III, incomplete right bundle branch block (RBBB), T-wave inversion (TWI) in leads
      V1-V3, ST elevation in leads aVR and V1, and ST depression in leads I, II, III,
      aVF, and V4-V6. These characteristic ECG changes might have prognostic value for
      clinical deterioration. He recovered after treatment. After discharge, the ECG
      showed resolution of TWI in leads V1-V3 and incomplete RBBB, suggesting recovery
      from right ventricular dysfunction, which was confirmed by an echocardiogram on
      follow in the outpatient department.

PMID- 28757766
TI  - Clear cell carcinoma arising from scar endometriosis: A case report and
      literature review.
AB  - Scar endometriosis is uncommon and defined as the presence of ectopic endometrial
      glands in abdominal soft tissues after a gynecological operation. Malignant
      transformation has been reported but remains rare. Carcinogenesis occurs in
      ectopic endometrial tissue with repeated hormone stimulation during the menstrual
      cycle. We present a case of clear cell carcinoma directly arising from scar
      endometriosis after a cesarean section and review all 16 cases reported.

PMID- 28757767
TI  - Anesthesia for a patient with unexpected giant tracheobronchomegaly.
AB  - Tracheobronchomegaly (also called Mounier-Kuhn syndrome) is a rare disease
      characterized by flaccid and markedly dilated trachea and main bronchi on
      inspiration with narrowing or collapse on expiration or cough. It is associated
      with recurrent lower respiratory tract infection. A 75-year-old man with
      unexpected giant tracheomegaly had a significant peritubal air leak which impeded
      an operation. Lumbar epidural anesthesia was performed for a subsequent operation
      without any sequela. Careful evaluation with chest radiography is basic to
      exclude a large airway. Chest computed tomography and fiber-optic bronchoscopy
      provided the diagnosis of a large airway. If a large airway is suspected, these
      examinations help to evaluate and manage the airway.

PMID- 28757768
TI  - Langerhans cell histiocytosis of the bone.

PMID- 28757769
TI  - The borderland between normal aging and dementia.
AB  - Alzheimer's disease (AD) has become a global health issue as the population ages.
      There is no effective treatment to protect against its occurrence or progression.
      Some argue that the lack of treatment response is due to delays in diagnosis. By
      the time a diagnosis of AD is made, neurodegenerative changes are at the stage
      where very few neurons can be salvaged by medication. The AD research community
      has developed the idea of mild cognitive impairment (MCI) in an attempt to find
      predementia patients who might benefit from potentially therapeutic drugs that
      have proven ineffective in the past. However, MCI is heterogeneous in terms of
      its underlying pathology and practicality for predicting dementia. This article
      first reviews the conceptual evolution of MCI as the borderland between normal
      aging and dementia, and then proposes that built environment and sociocultural
      context are two key elements in formulating a diagnosis of dementia. Dementia is
      more than a biomedical term. Cognitive impairment is considered a dynamic outcome
      of how an individual interacts with cognitive challenges. To focus on amyloid
      deposition as a single etiology for AD does not adequately capture the social
      implications and geriatric aspects of dementia. Moreover, MCI is nosologically
      questionable. Unlike a diagnosis of AD, for which a prototype has been well
      established, MCI is defined by operational criteria and there are no cases seen
      as typical MCI. Biofluid and imaging markers are under active development for
      early detection of amyloid deposition and neurofibrillary tangles in the brain,
      whereas vascular risks, chronic medical diseases, and polypharmacy continue to
      add to the complexity of dementia in old age. The paradigm of dementia care
      policy may shift to early diagnosis of AD pathology and comprehensive care for
      chronic diseases in the elderly population.

PMID- 28757771
TI  - Pathophysiology of benign prostate enlargement and lower urinary tract symptoms:
      Current concepts.
AB  - Lower urinary tract symptoms (LUTS) are highly prevalent in the aging population,
      particularly in men. Historically, prostate enlargement was thought to be
      responsible for most cases of male LUTS. Several risk factors for the development
      of benign prostate enlargement/hyperplasia (BPE/BPH) have been identified,
      including age, genetics, hormones, growth factors, inflammation, and lifestyle
      factors. However, as our knowledge continues to evolve, male LUTS are no longer
      managed entirely in a prostate-centric fashion. In this article, we review
      current concepts in the epidemiology, etiology, and pathophysiology of BPE/BPH
      and male LUTS.

PMID- 28757770
TI  - Recent research on the role of urodynamic study in the diagnosis and treatment of
      male lower urinary tract symptoms and urinary incontinence.
AB  - Although evidence shows that urodynamic study may not improve outcomes, it can be
      used to evaluate men with lower urinary tract symptoms (LUTSs) which have not
      been adequately delineated and treated. In young men with LUTS not responding to
      treatment based on clinical examination, or elderly men with LUTS and
      incontinence, a complete urodynamic evaluation is mandatory to understand the
      pathophysiology underlying LUTS, such as bladder outlet obstruction (BOO),
      detrusor overactivity, and detrusor underactivity. Preoperative urodynamic study
      proven BOO is a predictor of a successful surgical outcome. An urodynamic study
      should be performed when patients with LUTS are planning to undergo surgical
      treatment for benign prostatic obstruction.

PMID- 28757772
TI  - Using high-resolution human leukocyte antigen typing of 11,423 randomized
      unrelated individuals to determine allelic varieties, deduce probable human
      leukocyte antigen haplotypes, and observe linkage disequilibria between human
      leukocyte antigen-B and-C and human leukocyte antigen-DRB1 and-DQB1 alleles in
      the Taiwanese Chinese population.
AB  - OBJECTIVE: We report here the human leukocyte antigen (HLA) allelic variety and
      haplotype composition in a cohort of the Taiwanese Chinese population and their
      patterns of linkage disequilibria on HLA-B: HLA-C alleles and HLA-DRB1: HLA-DQB1
      alleles at a high-resolution level. MATERIALS AND METHODS: Peripheral whole blood
      from 11,423 Taiwanese Chinese unrelated individuals was collected in acid citrate
      dextrose. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit. The DNA
      material was subjected to HLA genotyping for HLA-A,-B,-C,-DRB1, and-DQB1 loci
      using a commercial polymerase chain reaction-sequence-based typing (PCR-SBT) kit,
      the SeCore(r) A/B/C/DRB1/DQB1 Locus Sequencing kit. High-resolution allelic
      sequencing was performed as previously described. RESULTS: The number of
      individual HLA-B alleles detected was greater than the number of alleles
      recognized in the both the HLA-A and-DRB1 loci. Several novel alleles were
      discovered as a result of employing the SBT method and the high number of donors
      tested. In addition, we observed a genetic polymorphic feature of association
      between HLA-A and-B, HLA-B and-C, and HLA-DRB1 and-DQB1 alleles. Further, the
      homozygous haplotype frequencies of HLA-A and-B; HLA-A,-C, and-B; HLA-A,-C,-B,
      and-DRB1; and HLA-A,-C,-B,-DRB1, and-DQB1 in Taiwanese Chinese population are
      presented. CONCLUSION: As increasing number of HLA alleles are being discovered,
      periodic HLA profile investigation in a given population is essential to
      recognize the HLA complexity in that population. Population study can also
      provide an up-to-date strategic plan for future needs in terms of compatibility
      measurement for HLA matching between transplant donors and patients.

PMID- 28757773
TI  - Vascular burden and brain aging in a senior volunteer cohort: A pilot study.
AB  - OBJECTIVE: To test the feasibility of establishing a senior volunteer cohort and
      describe vascular risks, cognitive function, and brain aging indices in a pilot
      study. MATERIALS AND METHODS: We enrolled 40 senior volunteers from the Tzu Chi
      Foundation and other organizations in Hualien in 2014-2015. We conducted in
      person interviews to collect information on demographic features, physical
      fitness, dietary habits, comorbidities, and narratives of aging. Vascular risks
      including blood pressure, body mass index (BMI), serum glucose level, and lipid
      profile were examined. Each participant underwent a comprehensive battery of
      neuropsychological tests and structural brain magnetic resonance imaging (MRI).
      Descriptive statistics and tabulation were applied to characterize this pilot
      cohort. RESULTS: There were more volunteers from the Tzu Chi Foundation (n = 25)
      than other organizations. The mean age was 66.7 years (standard deviation = 5.1)
      and there was a female predominance (M:F = 13:27). The mean number of comorbid
      chronic diseases was 2.1 and the mean BMI was 24.5. Most participants (77.5%)
      engaged in outdoor walking activities every week. Nutrient intake in vegetarians
      (n = 18) did not differ from nonvegetarians except for lower Vitamin B12 levels
      (mean = 0.9 MUg). All participants but one scored 26 or above in the Mini-Mental
      State Examination (mean = 28.4). Among the other cognitive tests, only one task
      related to inhibition and switching abilities was at the low average level. The
      mean values of vascular risk markers were within the normal ranges. The most
      common genotype of apolipoprotein E was E3/E3 (n = 32). The quality of MRI was
      sufficient for volumetric analysis. CONCLUSION: It is feasible to establish a
      volunteer-based cohort to study brain aging in Taiwan. The senior volunteers were
      physically active and cognitively healthy. Vascular risks were well distributed
      among these participants. Future longitudinal study will allow us to observe
      changes in these markers over time and provide dynamic evidence about vascular
      health and cognitive aging.

PMID- 28757774
TI  - Prevalence, risk factors, and antimalarial resistance patterns of falciparum
      plasmodiasis among pregnant women in Kaduna metropolis, Nigeria.
AB  - OBJECTIVE: Pregnant women infected with malaria represent a significant obstetric
      problem, especially in the face of antimalarial resistance. This cross-sectional
      study investigated the prevalence of malaria parasitemia, associated risk factors
      as well as the antimalarial resistance pattern of Plasmodium isolates from
      pregnant women attending four selected secondary health facilities in Kaduna
      State, Nigeria. MATERIALS AND METHODS: Blood samples were collected from 353
      pregnant women attending selected hospitals. Malaria microscopy and parasite
      density count were conducted based on standard protocols. Antimalarial
      susceptibility test (using chloroquine, artesunate, artether, and sulfadoxine
      pyrimethamine), and hemoglobin concentrations were determined using schizont
      maturation assay and methemoglobin method, respectively. Multiple-drug resistance
      (MDR) was defined by resistance against >=3 antimalarial drugs. RESULTS: The
      overall prevalence of plasmodiasis was 22.4%. Out of those infected, 5.2% was
      found to be anemic. Malaria parasitemia was significantly associated with parity,
      residential area, age of women, and use of preventive measures against malaria (P
      < 0.05) but not with hemoglobin concentration, occupation, and trimester of
      pregnancy (P > 0.05). Malaria parasites from the pregnant women exhibited the
      highest resistance against chloroquine, 75 (94.9%) followed Artemether, 30
      (37.9%) then sulfadoxine-pyrimethamine, 29 (36.7%) and least resistant to
      artesunate, 28 (35.4%). The prevalence of MDR was 40.5% (32/79). CONCLUSION: The
      prevalence of malaria was relatively high due to inadequate and/or ineffective
      preventive measures adopted by pregnant women. More so, significant isolates of
      Plasmodium falciparum exhibited MDR against antimalarial agents tested.

PMID- 28757775
TI  - An anatomical study of the proximal aspect of the medial femoral condyle to
      define the proximal-distal condylar length.
AB  - OBJECTIVE: Despite its possible role in knee arthroplasty, the proximal-distal
      condylar length (PDCL) of the femur has never been reported in the literature. We
      conducted an anatomic study of the proximal aspect of the medial femoral condyle
      to propose a method for measuring the PDCL. MATERIALS AND METHODS: Inspection of
      dried bone specimens was carried out to assure the most proximal condylar margin
      (MPCM) as the eligible starting point to measure the PDCL. Simulation surgery was
      performed on seven pairs of cadaveric knees to verify the clinical application of
      measuring the PDCL after locating the MPCM. Interobserver reliability of this
      procedure was also analyzed. RESULTS: Observation of the bone specimens showed
      that the MPCM is a concavity formed by the junction of the distal end of the
      supracondylar ridge and the proximal margin of the medial condyle. This
      anatomically distinctive structure made the MPCM an unambiguous landmark. The
      cadaveric simulation surgical dissection demonstrated that the MPCM is easily
      accessed in a surgical setting, making the measurement of the PDCL plausible. The
      intraclass correlation coefficient was 0.78, indicating good interobserver
      reliability for this technique. CONCLUSION: This study has suggested that the
      PDCL can be measured based on the MPCM in a surgical setting. PDCL measurement
      might be useful in joint line position management, selection of femoral component
      sizes, and other applications related to the proximal-distal dimension of the
      knee. Further investigation is required.

PMID- 28757777
TI  - Delusions of control in a case of schizophrenia coexisting with a large
      cerebellar arachnoid cyst.
AB  - Arachnoid cyst is a benign, congenital space-occupying brain lesion, which has
      been found in patients with schizophrenia. The association between arachnoid cyst
      and schizophrenia remains controversial, but the location of the arachnoid cyst
      may give rise to a specific symptom presentation in schizophrenia. We present a
      31-year-old woman with an established diagnosis of schizophrenia coexisting with
      a large cerebellar arachnoid cyst who presented mainly with delusions of control.
      This cerebellar arachnoid cyst and schizophrenia may have been found together
      coincidentally or brain dysfunction due to this cerebellar arachnoid cyst may
      have caused or contributed to the appearance of psychotic symptoms. The patient
      had an unsteady gait accompanied by delusions of control, and she showed a poor
      response to high-dose olanzapine treatment, suggesting the arachnoid cyst was
      associated with her schizophrenic symptoms. The cyst was over the right posterior
      fossa with cerebellum compression, which may have caused abnormality in the
      cerebellar-parietal network resulting in her delusions of control. This case
      indicates that there might be relationships between cerebellar lesions,
      schizophrenia, and delusions of control.

PMID- 28757776
TI  - Leptin is an independent marker of metabolic syndrome in elderly adults with type
      2 diabetes.
AB  - OBJECTIVE: It is well established that patients with metabolic syndrome (MetS)
      demonstrate elevated levels of serum leptin. The aim of this study is to identify
      fasting serum leptin as an independent marker of MetS in geriatric diabetic
      patients. MATERIALS AND METHODS: Sixty-four patients over 65 years old with type
      2 diabetic mellitus (T2DM) were assessed for MetS based on the diagnostic
      criteria of the International Diabetes Federation. Fasting blood samples
      including serum leptin concentrations were obtained from the participants. Leptin
      levels were determined using a commercial enzyme immunoassay. RESULTS: Forty-five
      (70.3%) of the 64 geriatric T2DM patients enrolled in this study were found to
      have MetS. This group of participants compared with those in the non-MetS group
      had higher serum levels of leptin (P = 0.004), triglycerides (P = 0.005), fasting
      glucose (P = 0.049), glycated hemoglobin (P = 0.016), white blood cells (P =
      0.003), C-reactive protein (CRP, P = 0.028), insulin (P < 0.001), higher
      homeostatic model assessment insulin resistance values (HOMA1-IR and HOMA2-IR,
      both P < 0.001), a higher body weight (P = 0.024), body mass index (P < 0.001),
      body fat mass (P < 0.001), waist circumference (P < 0.001), systolic blood
      pressure (BP) (P < 0.001), diastolic BP (P < 0.001), percentage of women (P =
      0.011), prevalence of hypertension (P = 0.042), and a lower level of serum high
      density lipoprotein cholesterol (P = 0.001). Univariate linear analysis of the
      clinical variables associated with the fasting serum leptin level revealed that
      height (P = 0.020) had a negative correlation, while body fat mass (P < 0.001)
      and logarithmically transformed CRP (log-CRP, P < 0.001) had positive
      correlations with serum leptin levels. Multivariate forward step-wise linear
      regression analysis of the variables significantly associated with fasting serum
      leptin levels showed that body fat mass (P < 0.001) and log-CRP (P = 0.001) were
      independent predictors of these values. CONCLUSION: Serum leptin is positively
      correlated with MetS. It serves as an independent marker of MetS in elderly
      patients with T2DM.

PMID- 28757778
TI  - Pneumomediastinum: An unusual complication after percutaneous nephrolithotomy.
AB  - Pneumomediastinum is the presence of air within the mediastinum. It is usually
      caused by a respiratory tract disorder, esophageal erosion, bowel perforation, or
      gastrointestinal tract endoscopic procedure. Pneumomediastinum following
      urological endoscopic surgery is very uncommon. Here, we report an unusual case
      of pneumomediastinum in a 55-year-old female following percutaneous
      nephrolithotomy for renal and ureteral stones. The patient recovered well with
      supportive treatment with oxygen.

PMID- 28757779
TI  - Symmetrical peripheral gangrene in sepsis after treatment with inotropes.
AB  - Symmetrical peripheral gangrene (SPG) is characterized by sudden onset of
      peripheral, frequently symmetrical, gangrene in the absence of major vascular
      occlusive disease. We report a case of four limb SPG caused by septic shock with
      disseminated intravascular coagulation (DIC) that had been treated with
      inotropes. This case shows that SPG may be present as a complication of sepsis
      due to systematic derangement that affects a wide range of organ systems,
      including coagulation and microcirculation. Early recognition and prompt
      management of sepsis and optimization of the process of weaning off the inotropes
      at the earliest opportunity are necessary to avoid SPG.

PMID- 28757780
TI  - Primary lymphoepithelioma-like carcinoma of the urinary bladder.

PMID- 28757781
TI  - Type B Wellens' syndrome: Electrocardiogram patterns that clinicians should be
      aware of.

PMID- 28757782
TI  - Incarcerated Amyand's hernia.

PMID- 28757784
TI  - On a more accurate Hardy-Mulholland-type inequality.
AB  - By using the way of weight coefficients, the technique of real analysis, and
      Hermite-Hadamard's inequality, a more accurate Hardy-Mulholland-type inequality
      with multi-parameters and a best possible constant factor is given. The
      equivalent forms, the reverses, the operator expressions and some particular
      cases are considered.

PMID- 28757783
TI  - Weighted quantitative isoperimetric inequalities in the Grushin space [Formula:
      see text] with density [Formula: see text].
AB  - In this paper, we prove weighted quantitative isoperimetric inequalities for the
      set [Formula: see text] in half-cylinders in the Grushin space [Formula: see
      text] with density [Formula: see text], [Formula: see text].

PMID- 28757785
TI  - The approximation of Laplace-Stieltjes transforms with finite order.
AB  - In this paper, we study the irregular growth of an entire function defined by the
      Laplace-Stieltjes transform of finite order convergent in the whole complex plane
      and obtain some results about lambda-lower type. In addition, we also investigate
      the problem on the error in approximating entire functions defined by the Laplace
      Stieltjes transforms. Some results about the irregular growth, the error, and the
      coefficients of Laplace-Stieltjes transforms are obtained; they are
      generalization and improvement of the previous conclusions given by Luo and Kong,
      Singhal and Srivastava.

PMID- 28757786
TI  - Some new results on convex sequences.
AB  - In the present paper, we obtained a main theorem related to factored infinite
      series. Some new results are also deduced.

PMID- 28757787
TI  - The Influence of Post-Build Microstructure on the Electrochemical Behavior of
      Additively Manufactured 17-4 PH Stainless Steel.
AB  - The additive manufacturing (AM) build process produces a segregated
      microstructure with significant variations in composition and phases that are
      uncommon in traditional wrought materials. As such, the relationship between the
      post-build microstructure and the corrosion resistance is not well understood.
      Stainless steel alloy 17-4PH is an industrially-relevant alloy for applications
      requiring high-strength and good corrosion resistance. A series of
      potentiodynamic scans conducted in a deaerated 0.5 mol/L NaCl solution evaluated
      the influence of these microstructural differences on the pitting behavior of
      SS17-4. The pitting potentials were found to be higher in the samples of
      additively-processed material than in samples of the alloy in wrought form. This
      indicates that the additively-processed material is more resistant to localized
      corrosion and pitting in this environment than the wrought alloy. The results
      also suggest that after homogenization, the additively-produced SS17-4 could be
      more resistant to pitting than wrought SS17-4 in an actual service environment.

PMID- 28757788
TI  - Bidirectional Effects of Positive Affect, Warmth, and Interactions Between
      Mothers With and Without Symptoms of Depression and Their Toddlers.
AB  - Maternal depression has negative implications for parenting and child outcomes,
      but it is also important to understand the daily transactional interactions that
      occur between mothers varying in symptoms of depression and their children. The
      current study aimed to examine immediate bidirectional effects between maternal
      warmth and positive affect and toddler affect in a sample of mothers varying in
      symptoms of depression. Ninety-one mothers and their 24-month-old toddlers
      completed a laboratory free-play/clean-up task. Mothers rated their symptoms of
      depression using the CES-D, and maternal warmth and positive affect and toddler
      positive and negative affect were observationally coded from a free-play and
      clean-up laboratory task. Sequential analyses indicated that mothers with no or
      mild symptoms of depression exhibited mutual positive affect with their children,
      but mothers with more severe symptoms of depression did not. Mothers with higher
      symptoms of depression displayed a decrease in warmth concurrent with toddlers'
      positive affect. Further, unlike dyads in which mothers had higher symptoms of
      depression, dyads of mothers with lower symptoms appeared to exhibit some
      covariation in positive affect across the episode. These results provide evidence
      that even in non-clinical samples, affective manifestations of mothers'
      subthreshold levels of depression may have negative immediate effects on
      toddlers' emotions, and that mothers without symptoms of depression may have more
      reciprocal affective exchanges with their toddlers.

PMID- 28757789
TI  - Estimating the microbiological risks associated with inland flood events:
      Bridging theory and models of pathogen transport.
AB  - Flooding is known to facilitate infectious disease transmission, yet quantitative
      research on microbiological risks associated with floods has been limited.
      Pathogen fate and transport models provide a framework to examine interactions
      between landscape characteristics, hydrology, and waterborne disease risks, but
      have not been widely developed for flood conditions. We critically examine
      capabilities of current hydrological models to represent unusual flow paths, non
      uniform flow depths, and unsteady flow velocities that accompany flooding. We
      investigate the theoretical linkages between hydrodynamic processes and spatio
      temporally variable suspension and deposition of pathogens from soils and
      sediments; pathogen dispersion in flow; and concentrations of constituents
      influencing pathogen transport and persistence. Identifying gaps in knowledge and
      modeling practice, we propose a research agenda to strengthen microbial fate and
      transport modeling applied to inland floods: 1) development of models
      incorporating pathogen discharges from flooded sources (e.g., latrines), effects
      of transported constituents on pathogen persistence, and supply-limited pathogen
      transport; 2) studies assessing parameter identifiability and comparing model
      performance under varying degrees of process representation, in a range of
      settings; 3) development of remotely sensed datasets to support modeling of
      vulnerable, data-poor regions; and 4) collaboration between modelers and field
      based researchers to expand the collection of useful data in situ.

PMID- 28757790
TI  - Improving Factor Score Estimation Through the Use of Observed Background
      Characteristics.
AB  - A challenge facing nearly all studies in the psychological sciences is how to
      best combine multiple items into a valid and reliable score to be used in
      subsequent modelling. The most ubiquitous method is to compute a mean of items,
      but more contemporary approaches use various forms of latent score estimation.
      Regardless of approach, outside of large-scale testing applications, scoring
      models rarely include background characteristics to improve score quality. The
      current paper used a Monte Carlo simulation design to study score quality for
      different psychometric models that did and did not include covariates across
      levels of sample size, number of items, and degree of measurement invariance. The
      inclusion of covariates improved score quality for nearly all design factors, and
      in no case did the covariates degrade score quality relative to not considering
      the influences at all. Results suggest that the inclusion of observed covariates
      can improve factor score estimation.

PMID- 28757791
TI  - Multimedia Field Test Thinking About Exposures? There's an App for That!
AB  - Anxiety Coach is a smartphone application ("app") for iOS devices that is billed
      as a self-help program for anxiety in youth and adults. The app is currently
      available in the iTunes store for a one-time fee of $4.99. Anxiety Coach is
      organized around three related content areas: (a) self-monitoring of anxiety
      symptoms, (b) learning about anxiety and its treatment, and (c) guiding users
      through the development of a fear hierarchy and completion of exposure tasks.
      Although the app includes psychoeducation about anxiety as well as information
      regarding specific skills individuals can use to cope with anxiety (e.g.,
      cognitive restructuring), the primary focus of the app is on exposure tasks. As
      such, the app includes a large library of potential exposure tasks that are
      relevant to treating common fears and worries, making Anxiety Coach useful to
      clients and clinicians alike. Additionally, Anxiety Coach prompts users to
      provide fear ratings while they are carrying out an exposure task and displays a
      message instructing users to stop the exposure once fear ratings drop by half.
      These features work together to create an app that has the potential to greatly
      increase the reach of exposure-based cognitive behavioral therapy for anxiety.

PMID- 28757792
TI  - A Heart Failure Management Program Using Shared Medical Appointments.
AB  - BACKGROUND: Disease management programs for heart failure (HF) effectively reduce
      HF-related hospitalization rates and mortality. Shared medical appointments
      (SMAs) offer a cost-effective delivery method for HF disease management programs.
      However, few studies have evaluated this cost-effective delivery method of HF
      disease management among Veterans with acute HF. We hypothesized that Veterans
      who attended a multidisciplinary HF-SMA clinic promoting HF self-management,
      compared those who only received individual treatment through the HF specialty
      clinic, would have better 12-month hospitalization outcomes. METHODS: We
      completed a retrospective review of the VA electronic health record for HF-SMA
      clinic appointments (1/1/2012 to 12/31/2013). The multidisciplinary HF-SMA
      program comprised 4 weekly sessions covering topics including HF disease, HF
      medications, diet adherence, physical activity, psychological well-being, and
      stress management. Patients who attended the HF-SMA clinic (n=54) were compared
      to patients who were scheduled for an HF-SMA appointment but never attended and
      were followed only in the HF clinic (n=37). Outcomes were 12-month HF-related and
      all-cause hospitalization rates, days in the hospital, and time to first
      hospitalization. RESULTS: Of 141 patients scheduled for an HF-SMA clinic
      appointment, 54 met criteria for the HF-SMA clinic group and 37 were included in
      the HF clinic group. The groups did not significantly differ on any
      sociodemographic variables. Furthermore, no significant differences were observed
      between the HF-SMA group and the HF clinic group on demographics or
      hospitalization outcomes, p>.05 for all comparisons. CONCLUSIONS: Our results did
      not support our hypothesis that offering multidisciplinary, HF-SMAs promoting HF
      self-management skills, above and beyond the individual disease management care
      provided in an HF specialty clinic, would improve hospitalization outcomes among
      Veterans with acute HF. Limitations of the present study and recommendations for
      HF self-management programs for Veterans are discussed.

PMID- 28757793
TI  - A Mortality Study for ICU Patients using Bursty Medical Events.
AB  - The study of patients in Intensive Care Units (ICUs) is a crucial task in
      critical care research which has significant implications both in identifying
      clinical risk factors and defining institutional guidances. The mortality study
      of ICU patients is of particular interest because it provides useful indications
      to healthcare institutions for improving patients experience, internal policies,
      and procedures (e.g. allocation of resources). To this end, many research works
      have been focused on the length of stay (LOS) for ICU patients as a feature for
      studying the mortality. In this work, we propose a novel mortality study based on
      the notion of burstiness, where the temporal information of patients longitudinal
      data is taken into consideration. The burstiness of temporal data is a popular
      measure in network analysis and time-series anomaly detection, where high values
      of burstiness indicate presence of rapidly occurring events in short time periods
      (i.e. burst). Our intuition is that these bursts may relate to possible
      complications in the patient's medical condition and hence provide indications on
      the mortality. Compared to the LOS, the burstiness parameter captures the
      temporality of the medical events providing information about the overall dynamic
      of the patients condition. To the best of our knowledge, we are the first to
      apply the burstiness measure in the clinical research domain. Our preliminary
      results on a real dataset show that patients with high values of burstiness tend
      to have higher mortality rate compared to patients with more regular medical
      events. Overall, our study shows promising results and provides useful insights
      for developing predictive models on temporal data and advancing modern critical
      care medicine.

PMID- 28757794
TI  - Calculating Iso-Committor Surfaces as Optimal Reaction Coordinates with
      Milestoning.
AB  - Reaction coordinates are vital tools for qualitative and quantitative analysis of
      molecular processes. They provide a simple picture of reaction progress and
      essential input for calculations of free energies and rates. Iso-committor
      surfaces are considered the optimal reaction coordinate. We present an algorithm
      to compute efficiently a sequence of isocommittor surfaces. These surfaces are
      considered an optimal reaction coordinate. The algorithm analyzes Milestoning
      results to determine the committor function. It requires only the transition
      probabilities between the milestones, and not transition times. We discuss the
      following numerical examples: (i) a transition in the Mueller potential; (ii) a
      conformational change of a solvated peptide; and (iii) cholesterol aggregation in
      membranes.

PMID- 28757795
TI  - A New Model to Study Fatigue in Dental Implants Based on Probabilistic Finite
      Elements and Cumulative Damage Model.
AB  - The aim of this study was to predict the fatigue life of two different
      connections of a dental implant as in load transfer to bone. Two three
      dimensional models were created and assembled. All models were subjected to a
      natural masticatory force of 118 N in the angle of 75 degrees  to the occlusal
      plane. All degrees of freedom in the inferior border of the cortical bone were
      restrained, and the mesial and distal borders of the end of the bone section were
      constrained. Fatigue material data and loads were assumed as random variables.
      Maximum principal stresses on bone were evaluated. Then, the probability of
      failure was obtained by the probabilistic approach. The maximum principal stress
      distribution predicted in the cortical and trabecular bone is 32 MPa for external
      connection and 39 MPa for internal connection. A mean life of 103 and 210 million
      cycles were obtained for external and internal connection, respectively.
      Probability cumulative function was also evaluated for both connection types.
      This stochastic model employs a cumulative damage model and probabilistic finite
      element method. This methodology allows the possibility of measured uncertainties
      and has a good precision on the results.

PMID- 28757796
TI  - Bionic Design for Reducing Adhesive Resistance of the Ridger Inspired by a Boar's
      Head.
AB  - The main feature of the boar's head used to root around for food is the front
      part, which is similar to the ridger in terms of function, load, and environment.
      In this paper, the boar's head was selected as the biological prototype for
      developing a new ridger. The point cloud of the head was captured by a 3D
      scanner, and then, the head surface was reconstructed using 3D coordinates. The
      characteristic curves of the front part of the boar's head were extracted, and
      then, five cross-sectional curves and one vertical section curve were fitted.
      Based on the fitted curves, five kinds of bionic ridgers were designed. The
      penetrating resistances of the bionic ridgers and traditional ridger were tested
      at different speeds in an indoor soil bin. The test results showed that bionic
      ridger B had the best penetrating resistance reduction ratio of 16.67% at 4.2
      km/h velocity. In order to further evaluate the performance of the best bionic
      ridger (bionic ridger B), both the bionic ridger and traditional ridger were
      tested in a field under the same working conditions. The field results indicate
      that the bionic ridger reduces penetrating resistance by 6.91% compared to the
      traditional ridger, and the test results validate that the bionic ridger has an
      effect on reducing penetrating resistance.

PMID- 28757797
TI  - Reverse Nearest Neighbor Search on a Protein-Protein Interaction Network to Infer
      Protein-Disease Associations.
AB  - The associations between proteins and diseases are crucial information for
      investigating pathological mechanisms. However, the number of known and reliable
      protein-disease associations is quite small. In this study, an analysis framework
      to infer associations between proteins and diseases was developed based on a
      large data set of a human protein-protein interaction network integrating an
      effective network search, namely, the reverse k-nearest neighbor (RkNN) search.
      The RkNN search was used to identify an impact of a protein on other proteins.
      Then, associations between proteins and diseases were inferred statistically. The
      method using the RkNN search yielded a much higher precision than a random
      selection, standard nearest neighbor search, or when applying the method to a
      random protein-protein interaction network. All protein-disease pair candidates
      were verified by a literature search. Supporting evidence for 596 pairs was
      identified. In addition, cluster analysis of these candidates revealed 10
      promising groups of diseases to be further investigated experimentally. This
      method can be used to identify novel associations to better understand complex
      relationships between proteins and diseases.

PMID- 28757798
TI  - Mitral Valve Replacement-Current and Future Perspectives.
AB  - The favorable outcomes achieved with modern mitral valve repair techniques
      redefined the role of mitral valve replacement. Various international databases
      report a significant decrease in replacement procedures performed compared with
      repairs, and contemporary guidelines limit the application of surgical mitral
      valve replacement to pathology in which durable repair is unlikely to be
      achieved. The progressive paradigm shift toward endoscopic and robotic mitral
      valve surgery is also paralleled by rapid developments in transcatheter devices,
      which is progressively expanding from experimental approaches to becoming
      clinical reality. This article outlines the current role and future perspectives
      of contemporary surgical mitral valve replacement within the context of mitral
      valve repair and the dynamic evolution of exciting transcatheter alternatives.

PMID- 28757799
TI  - Algorithm for Predicting Disease Likelihood From a Submaximal Exercise Test.
AB  - We developed a simplified automated algorithm to interpret noninvasive gas
      exchange in healthy subjects and patients with heart failure (HF, n = 12),
      pulmonary arterial hypertension (PAH, n = 11), chronic obstructive lung disease
      (OLD, n = 16), and restrictive lung disease (RLD, n = 12). They underwent
      spirometry and thereafter an incremental 3-minute step test where heart rate and
      SpO2 respiratory gas exchange were obtained. A custom-developed algorithm for
      each disease pathology was used to interpret outcomes. Each algorithm for HF,
      PAH, OLD, and RLD was capable of differentiating disease groups (P < .05) as well
      as healthy cohorts (n = 19, P < .05). In addition, this algorithm identified
      referral pathology and coexisting disease. Our primary finding was that the
      ranking algorithm worked well to identify the primary referral pathology;
      however, coexisting disease in many of these pathologies in some cases equally
      contributed to the cardiorespiratory abnormalities. Automated algorithms will
      help guide decision making and simplify a traditionally complex and often time
      consuming process.

PMID- 28757800
TI  - Case Report: Recurrent Mucoepidermoid Carcinoma of the Tongue in Adult Female
      Patient With Lung Cancer.
AB  - There is a steady rise in incidence of malignant salivary gland tumors in the
      United States, with mucoepidermoid carcinoma (MEC) the most frequent. Although
      40% of MECs are found in the parotid gland, these lesions possess the capacity to
      develop anywhere along the aerodigestive tract. Here, we present a case of
      recurrent tongue MEC in a young adult female patient with history of lung
      malignancy and multiple brain metastases. Without a universally accepted
      management protocol for recurrent MECs, the current clinical practice uses tumor
      grade, location, and clinical progression to determine both prognosis and goals
      of care. The patient had transoral laser excision of the first MEC lesion in
      2013. Her tongue MEC recurred 3 years later with 2 distinct lesions. One was
      discovered on physical examination and computed tomography and the other
      diagnosed intraoperatively 1 month later. These lesions were located on a
      previously unaffected portion of dorsal tongue base. These lesions were
      completely excised in the operating room. The patient currently remains on
      chemotherapy. This underscores the importance for developing a guideline that
      delineates the most efficacious surveillance and treatment plans for recurrent
      MECs.

PMID- 28757801
TI  - PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current
      evidence.
AB  - Gastric adenocarcinoma is a leading cause of global cancer-related morbidity and
      mortality, and new therapeutic approaches are needed. Despite the improved
      outcomes with monoclonal antibodies targeting human epidermal growth factor
      receptor 2 and vascular endothelial growth factor receptor 2, durable responses
      are uncommon. Targeting immune checkpoints including PD-1, PD-L1 and CTLA-4 have
      led to improved survival across several tumor types, frequently characterized by
      prolonged benefit in responding patients. Tumoral and lymphocyte-derived
      immunohistochemical staining for PD-1, PD-L1, and tumor mutational burden have
      shown potential as predictive response biomarkers in several tumor types. Optimal
      incorporation of immune-mediated therapies into gastric cancer (GC) is an area of
      intense ongoing investigation and benefit has been demonstrated in smaller
      studies of advanced patients. Important questions of biomarker selection, roles
      for molecular characterization, optimal combinatorial approaches, and therapeutic
      sequencing remain. In this study, current data are reviewed for immune checkpoint
      inhibitors in GC, and putative biomarkers, ongoing trials, and future
      considerations are discussed.

PMID- 28757802
TI  - The Evaluation of the Clinical Effects of Botulinum Toxin on Nocturnal Bruxism.
AB  - OBJECTIVES: Nocturnal bruxism can be managed by botulinum toxin (Botox(r)) in
      patients who have not responded to conservative treatment. The aim of this study
      was to evaluate the efficacy of botulinum toxin A (BTXA) in the treatment of
      nocturnal bruxism. MATERIAL AND METHODS: The retrospective study comprised 25
      female patients, aged 23-55 years (mean 35.84 +/- 8.41 years). All patients
      received a single injection of BTXA in the right and left masseters. Evaluation
      was made by Visual Analogue Scale (VAS) values, complaint duration, onset of
      effect, and duration of effectiveness. RESULTS: BTXA produced significant
      improvements in pain scores. Only 2 adverse events (8%) were recorded.
      CONCLUSION: BTX-A is effective in the treatment of nocturnal bruxism.

PMID- 28757803
TI  - Low-Temperature Curing Strength Enhancement in Cement-Based Materials Containing
      Limestone Powder.
AB  - With the ongoing sustainability movement, the incorporation of limestone powder
      in cementitious binders for concrete in the U.S. has become a subject of renewed
      interest. In addition to accelerating the early age hydration reactions of
      cementitious systems by providing additional surfaces for nucleation and growth
      of products, limestone powder is also intriguing based on its influence on low
      temperature curing. For example, previous results have indicated that the
      utilization of limestone powder to replace one quarter of the fly ash in a high
      volume fly ash mixture (40 % to 60 % cement replacement) produces a reduction in
      the apparent activation energy for setting for temperatures below 25  degrees C.
      In the present study, the relationship between heat release and compressive
      strength of mortars at batching/curing temperatures of 10  degrees C and 23 
      degrees C is investigated. For Portland-limestone cements (PLC) with limestone
      additions on the order of 10 %, a higher strength per unit heat release is
      obtained after only 7 d of curing in lime water. Surprisingly, in some cases, the
      absolute strength of these mortar cubes measured at 7 d is higher when cured at
      10  degrees C than at 23  degrees C. Solubilities vs. temperature, reaction
      stoichiometries and enthalpies, and projected phase distributions based on
      thermodynamic modeling for the cementitious phases are examined to provide some
      theoretical insight into this strength enhancement. For a subset of the
      investigated cements, thermogravimetric analysis (TGA), quantitative X-ray
      diffraction (XRD), and scanning electron microscopy (SEM) are conducted on 7-d
      paste specimens produced at the two temperatures to examine differences in their
      reaction rates and the phases produced. The strength enhancement observed in the
      PLC cements is related to the cement hydration products formed in the presence of
      carbonates as a function of temperature.

PMID- 28757804
TI  - Enantioselective Syntheses of (-)-Alloyohimbane and (-)-Yohimbane by an Efficient
      Enzymatic Desymmetrization Process.
AB  - Enantioselective syntheses of (-)-alloyohimbane and (-)-yohimbane was
      accomplished in a convergent manner. The key step involved a modified mild
      protocol for the enantioselective enzymatic desymmetrization of meso-diacetate.
      The protocol provided convenient access to an optically active monoacetate in
      multi-gram scale in high enantiomeric purity. This monoacetate was converted to (
      )-alloyohimbane. Reductive amination of the derived aldehyde causes the
      isomerization leading to the trans-product and allows the synthesis of (-)
      yohimbane.

PMID- 28757805
TI  - Drinking context and alcohol's harm from others among men and women in the 2010
      US National Alcohol Survey.
AB  - BACKGROUND: Little is known about how drinking in different contexts is
      associated with harms from someone else's drinking, including marital problems,
      financial problems, and assault. We examined how drinking in four different
      contexts was associated with alcohol's harm from others (AHFO). METHODS: We
      utilized the landline sample of the 2010 US National Alcohol Survey (n = 5,885)
      to examine associations between drinking context and AHFO using weighted binary
      logistic regression. RESULTS: For women, drinking when friends dropped over was
      positively associated with assault and financial troubles due to someone else's
      drinking. Drinking when friends dropped over was negatively associated with
      assault for men. For men, drinking at a bar, party, or during a quiet evening at
      home were each significantly associated with more assault by someone who had been
      drinking. Bar drinking among women was significantly associated with more marital
      problems, whereas drinking at a party at someone else's home was associated with
      significantly less marital problems. CONCLUSIONS: Context-specific drinking has
      differential associations with specific types of harms from someone else's
      drinking for men and women. Additional research on drinking context, relationship
      to the harmer, and violence experienced by men and women is needed.

PMID- 28757806
TI  - Distress and alcohol-related harms from intimates, friends, and strangers.
AB  - Alcohol's harms to others (AHTO) has gained increased research and policy
      attention, yet little information is available on different social relationships
      involved in such harms or consequences of harms perpetrated by various types of
      drinkers. Using data from the 2014-15 U.S. National Alcohol Survey (N=5,922), we
      present analyses comparing frequency and impacts of eight past-year harms from
      other drinkers. In this sample (53% female; 66% White/Caucasian, 13%
      Black/African American, and 15% other race; 15% Hispanic/Latino of any race; mean
      age=47 years), 19% reported at least one harm in the prior 12 months, 8% reported
      more than one harm, 4.9% reported a family perpetrator, 3.5% a spouse
      perpetrator, 6.1% a friend perpetrator, and 8.1% a stranger perpetrator.
      Controlling for basic demographics, the number of harms in the past year and
      harms perpetrated by known others (but not strangers) were significantly
      associated with recent distress. When comparing specific harms, financial
      problems due to a family member's or a spouse/partner's drinking each were
      associated with significantly greater distress, as were feeling threatened or
      afraid of family members, spouses/partners or friends who had been drinking.
      These new data shed light on possible intervention points to reduce negative
      impacts of AHTO in the U.S.

PMID- 28757807
TI  - A report of nontraumatic cortical subarachnoid hemorrhage and subsequent
      management.
AB  - AIM: Report a case of cortical subarachnoid hemorrhage (cSAH) and discuss its
      management. PATIENT & METHODS: A 66-year-old woman presents with acute onset left
      arm numbness and weakness. Initial head CT shows small hyperdensity in sulci
      typical for cSAH. Extensive workup with MRI, lumbar puncture and blood tests is
      performed. No signs of infection, vascular malformations, thrombosis or cancer
      are found. At outpatient follow-up, she is diagnosed with cSAH secondary to
      amyloid angiopathy. She is treated with gabapentin. RESULTS & CONCLUSION:
      Diagnosis of cSAH is challenging given its subtle findings, and management is
      empiric as there are only a few case series in literature.

PMID- 28757808
TI  - What Should I Do? Behavior Regulation by Language and Paralanguage in Early
      Childhood.
AB  - This article explores the functional significance of affective messages for
      behavior in early childhood. Previous research indicates that children's
      affective judgments are influenced more by what is said than by how it is said.
      Of particular interest is the extent to which this tendency toward literal
      interpretation has real consequences for behavior. The effect of consistent and
      conflicting affective messages on child behavior was assessed in a social
      referencing procedure. What was said had a stronger effect than facial and vocal
      paralanguage on children's exploration of novel objects. This suggests that the
      lexical bias evident in children's interpretations reflects a genuine
      developmental transition in the primary cues on which attributions are based, and
      these cues have direct consequences for behavior regulation.

PMID- 28757810
TI  - The Influence of Women's Neighborhood Resources on Perceptions of Social
      Disorder.
AB  - Research links neighborhood social disorder with poorer health. But factors
      beyond observed disorder may influence perceptions that social disorder is
      problematic. This study investigates whether women's aggregate socioeconomic
      resources relative to men's in the broader neighborhood context attenuate the
      extent to which more prevalent observed social disorder within the immediate
      residential neighborhood contributes to perceptions of more problematic social
      disorder. This attenuation likely is pronounced among women, for whom sexual
      harassment in public spaces is a more salient concern compared to men. Using data
      from the Project on Human Development in Chicago Neighborhoods, multilevel models
      analyze individual perceptions of problematic social disorder (N=3,107) regressed
      on the interactive effect of observed social disorder within the census block
      group (N=525) and women's relative resources within the neighborhood cluster
      (N=80). The results show that women's relative resources within the broader
      neighborhood context protect against women's perceptions that typically
      undesirable neighborhood conditions are problematic.

PMID- 28757809
TI  - If You Go Down to the Woods Today: Infants' Distress During a Teddy Bear's Picnic
      in Relation to Peer Relations and Later Emotional Problems.
AB  - Infants' emotional reactions to an unusual event were assessed at a simulated
      birthday party during which two costumed characters enacted a Teddy Bear's
      Picnic. Two hundred and fifty-eight firstborn infants in a representative British
      community sample were observed at a mean age of 12.8 months in the presence of
      their parents and other participating families, in a laboratory sitting room
      decorated with balloons and banners. The picnic scenario was followed by free
      play with the other participating infants. At a mean of 36 months of age,
      mothers, fathers, and another informant who knew the child well completed the
      Child Behaviour Check List (CBCL). The majority of infants showed no vocal
      distress during the picnic scenario. A minority of infants expressed strong
      distress, which was correlated with elevated heart rate and production of
      cortisol. Infants who were not distressed were more likely to direct social
      behavior to their peers and especially likely to use physical force against
      peers. In comparison with strongly distressed and nondistressed infants, those
      who had shown mild distress during the picnic scenario were least likely to
      manifest later emotional problems. This pattern was particularly marked for boys.
      Taken together, the findings indicate that infants' strong distress during
      naturalistic encounters that are meant to be entertaining can suppress
      sociability and might indicate risk for subsequent emotional problems.

PMID- 28757811
TI  - Three-Dimensional Imaging by Self-Reference Single-Channel Digital Incoherent
      Holography.
AB  - Digital holography offers a reliable and fast method to image a three-dimensional
      scene from a single perspective. This article reviews recent developments of self
      reference single-channel incoherent hologram recorders. Hologram recorders in
      which both interfering beams, commonly referred to as the signal and the
      reference beams, originate from the same observed objects are considered as self
      reference systems. Moreover, the hologram recorders reviewed herein are
      configured in a setup of a single channel interferometer. This unique
      configuration is achieved through the use of one or more spatial light
      modulators.

PMID- 28757813
TI  - A QSAR Study Based on SVM for the Compound of Hydroxyl Benzoic Esters.
AB  - Hydroxyl benzoic esters are preservative, being widely used in food, medicine,
      and cosmetics. To explore the relationship between the molecular structure and
      antibacterial activity of these compounds and predict the compounds with similar
      structures, Quantitative Structure-Activity Relationship (QSAR) models of 25
      kinds of hydroxyl benzoic esters with the quantum chemical parameters and
      molecular connectivity indexes are built based on support vector machine (SVM) by
      using R language. The External Standard Deviation Error of Prediction (SDEPext),
      fitting correlation coefficient (R2), and leave-one-out cross-validation (Q2LOO)
      are used to value the reliability, stability, and predictive ability of models.
      The results show that R2 and Q2LOO of 4 kinds of nonlinear models are more than
      0.6 and SDEPext is 0.213, 0.222, 0.189, and 0.218, respectively. Compared with
      the multiple linear regression (MLR) model (R2 = 0.421, RSD = 0.260), the
      correlation coefficient and the standard deviation are both better than MLR. The
      reliability, stability, robustness, and external predictive ability of models are
      good, particularly of the model of linear kernel function and eps-regression
      type. This model can predict the antimicrobial activity of the compounds with
      similar structure in the applicability domain.

PMID- 28757814
TI  - A DFT Study of Structural and Bonding Properties of Complexes Obtained from First
      Row Transition Metal Chelation by 3-Alkyl-4-phenylacetylamino-4,5-dihydro-1H
      1,2,4-triazol-5-one and Its Derivatives.
AB  - Density functional calculations were used to explore the complexation of 3-alkyl
      4-phenylacetylamino-4,5-dihydro-1h-1,2,4-triazol-5-one (ADPHT) derivatives by
      first-row transition metal cations. Neutral ADPHT ligand and mono deprotonated
      ligands have been used. Geometry optimizations have been performed in gas-phase
      and solution-phase (water, benzene, and N,N-dimethylformamide (DMF)) with
      B3LYP/Mixed I (LanL2DZ for metal atom and 6-31+G(d,p) for C, N, O, and H atoms)
      and with B3LYP/Mixed II (6-31G(d) for metal atom and 6-31+G(d,p) for C, N, O, and
      H atoms) especially in the gas-phase. Single points have also been carried out at
      CCSD(T) level. The B3LYP/Mixed I method was used to calculate thermodynamic
      energies (energies, enthalpies, and Gibb energies) of the formation of the
      complexes analyzed. The B3LYP/Mixed I complexation energies in the gas phase are
      therefore compared to those obtained using B3LYP/Mixed II and CCSD(T)
      calculations. Our results pointed out that the deprotonation of the ligand
      increases the binding affinity independently of the metal cation used. The
      topological parameters yielded from Quantum Theory of Atom in Molecules (QTAIM)
      indicate that metal-ligand bonds are partly covalent. The significant reduction
      of the proton affinity (PA) observed when passing from ligands to complexes in
      gas-phase confirms the notable enhancement of antioxidant activities of neutral
      ligands.

PMID- 28757812
TI  - Calcium-Dependent Regulation of Ion Channels.
AB  - Calcium plays an important role in regulating hundreds of biological processes
      due to its primary role as one of the most ubiquitous second messengers. As a
      result, the levels of calcium are tightly regulated as are the peak and trough
      calcium concentrations during a calcium signal. Calcium levels are controlled via
      a variety of feedback mechanisms and exchangers/transporters. Here the role of
      calcium in the feedback regulation of ion channel function is reviewed, with an
      emphasis on the molecular mechanisms governing calcium-dependent function. In
      particular, the role of calcium in the regulation of voltage-gated sodium,
      calcium, and potassium channels are reviewed as well as its effects on the
      ryanodine receptor.

PMID- 28757816
TI  - Foreword of the Editor.

PMID- 28757817
TI  - Advances in the Diagnosis of Sepsis.

PMID- 28757815
TI  - Insulin induces a shift in lipid and primary carbon metabolites in a model of
      fasting-induced insulin resistance.
AB  - INTRODUCTION: Prolonged fasting in northern elephant seals (NES) is characterized
      by a reliance on lipid metabolism, conservation of protein, and reduced plasma
      insulin. During early fasting, glucose infusion previously reduced plasma free
      fatty acids (FFA); however, during late-fasting, it induced an atypical elevation
      in FFA despite comparable increases in insulin during both periods suggestive of
      a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion.
      OBJECTIVE: To better assess the contribution of insulin to this fasting
      associated shift in substrate metabolism. METHODS: We compared the responses of
      plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary
      carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late
      fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion
      (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and
      targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS
      technologies. RESULTS: In early fasting, the majority (72%) of metabolite
      trajectories return to baseline levels within 2 h, but not in late fasting
      indicative of an increase in tissue sensitivity to insulin. In late-fasting,
      increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate
      a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased
      protein catabolism. Conversely, insulin increased PCM AUC in late fasting
      suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA
      AUC between early and late fasting suggesting that insulin suppresses
      triglyceride hydrolysis. CONCLUSION: Naturally adapted tolerance to prolonged
      fasting in these mammals is likely accomplished by suppressing insulin levels and
      activity, providing novel insight on the evolution of insulin during a condition
      of temporary, reversible insulin resistance.

PMID- 28757818
TI  - Procalcitonin - Assisted Antibiotic Strategy in Sepsis.
AB  - Sepsis is one of the biggest challenges in critical care nowadays. Defining
      sepsis is a difficult task on its own and its diagnosis and treatment requires
      well trained, devoted personnel with interdisciplinary collaboration in order to
      provide the patients the best chance for survival. Immediate resuscitation, early
      adequate antimicrobial therapy, source control and highly sophisticated organ
      support on the intensive care units are all inevitable necessities for successful
      recovery. To help fast and accurate diagnosis biomarkers have been measured for
      decades. Procalcitonin (PCT) is one of the most studied, but the results are
      conflicting. Sepsis means a very loose cohort of a large heterogeneous patient
      population, hence defining certain cut off values for PCT to differentiate
      between different severities of the disease is almost impossible. Clinicians
      first have to understand the pathophysiological background of sepsis to be able
      to interpret correctly the PCT results. Nevertheless, PCT has been shown to have
      the best sensitivity and specificity to indicate infection, antibiotic
      appropriateness and stopping therapy. In this article we will focus on some
      important aspects of pathophysiology and advice on how to implement that in the
      everyday clinical practice. We believe that this multimodal evaluation of the
      clinical picture together with PCT results can be a useful tool to make the most
      out of the PCT results, and do the best for patients on the ICU.

PMID- 28757819
TI  - Advances and Pitfalls in Using Laboratory Biomarkers for the Diagnosis and
      Management of Sepsis.
AB  - Sepsis is a critical patient condition with high mortality rate caused by a
      complex and inadequate host response to infection. Since early identification and
      start of antibiotic therapy in the first few hours after sepsis development
      dramatically improves outcomes, it is of utter importance to offer fast, reliable
      and specific early laboratory biomarkers to help clinicians in sepsis
      recognition. On the other hand, the biomarkers should also be helpful in
      excluding sepsis and/or confirming therapy effectiveness, and thus prevent
      overprescribing of antibiotics. In this paper, we discuss the significance and
      relative merits of three currently available protein biomarkers: C-reactive
      protein, procalcitonin and presepsin. Although useful, none of these biomarkers
      has been shown to completely fulfill the roles mentioned above.

PMID- 28757821
TI  - Advances in the Diagnosis of Sepsis: Hydrogen Sulfide as a Prognostic Marker of
      Septic Shock Severity.
AB  - Hydrogen sulfide (H2S) is a third known gasotransmitter. Most of the time it was
      knows as a poisonous gas. In last 30 years, we are seeing change in its
      perception. Scientists have discovered its major role in different organ systems.
      It is endogenously produced in various tissues and its production is influenced
      by many factors. In normal, physiological conditions only 20% of H2S is in its
      free form. The role of H2S is very wide. It acts as a signaling molecule, has
      influence on vascular tone, inflammatory response, scavenges reactive oxygen
      species, can be cytoprotective and can even reduce the extent of myocardial
      ischemia. Different studies have shown H2S has considerable influence in
      pathology of sepsis and its outcome. High free plasma levels of H2S are predictor
      of unfavorable outcome. Findings show that moderate free plasma levels of H2S
      have protective effect. Paradoxical very low free plasma levels of H2S, seen in
      patients with chronic heart failure, are also predictor of severity of disease
      and poor outcome. We presume that relationship between morbidity/mortality and
      concentration of H2S has a wide U-shape curve dependence. New researches with
      discovery of H2S agonists and antagonists could open new ways in understanding
      different pathologies and ability to treat them. Recent advances in the
      identification of H2S agonists and antagonists may help in forwarding our
      understanding of pathomechanisms and hence their treatment.

PMID- 28757820
TI  - Nonconventional Markers of Sepsis.
AB  - Sepsis still remains a challenging healthcare problem with high mortality rate.
      To improve outcome, early diagnosis and monitoring of sepsis is of utmost
      importance. In this process objective laboratory parameters are the most helpful.
      Procalcitonin and C-reactive protein are the most commonly used and recommended
      markers of sepsis however, more than 200 sepsis biomarkers have already been
      published. This mini review focuses on nonconventional novel possibilities for
      the recognition of sepsis severity. Presepsin, actin and actin scavenger proteins
      (gelsolin and Gc-globulin) and orosomucoid are discussed. Besides serum
      parameters, the urinary levels of these markers are also elaborated, since
      urinary biomarkers of sepsis provide new diagnostic implications and are helpful
      for monitoring both the kidney function and the septic process. Increasing serum
      actin levels and decreasing levels of actin binding proteins seem to be
      associated with sepsis severity and outcome. Actin can be detected in the urine
      samples of septic patients as well, and strongly elevated levels of it were found
      in sepsis-related acute kidney injury. Both serum and urinary orosomucoid might
      be able to indicate sepsis, however urinary orosomucoid is a more sensitive
      inflammatory marker. Novel laboratory tests can provide rapid help for clinical
      decision making because the key point in successful treatment lies in the early
      diagnosis of sepsis.

PMID- 28757822
TI  - A Validation Study of After Reconstitution Stability of Diabetes: Level 1 and
      Diabetes Level 2 Controls.
AB  - OBJECTIVE: The after reconstitution stability of L1 & L2 is 7 days when stored at
      2 degrees -8 degrees c and tightly capped. The total content of the vial is 500
      uL and per test requirement is 5 uL. Hence, in 7 days laboratories would consume
      only 35 uL wasting 365 uL which is 73% of the expensive control samples and such
      wastage should be ideally prevented. The study of after reconstitution stability
      proved the stability of the control samples up to 90 days resulting in proper
      utilization of L1 & L2. MATERIALS AND METHODS: The L1 & L2 controls were
      reconstituted using 500 uL deionized water. The vials were allowed to stand for 5
      10 minutes, swirled 8-10 times to maintain the homogeneity. Aliquots of 10 uL
      were prepared. One aliquot of one control level being used per day, both levels
      on alternate day. 5 uL control is mixed with 1.5 mL diluent and HbA1c was tested
      in D10 system by HPLC method. Therefore, 500uL may be utilized up to 45 days
      approximately provided the extended use of control run is not affecting quality
      of test results. The minimum number of samples tested by the laboratory from a
      single vial is 45 and maximum 46. RESULTS: Three lots were tested of which one
      lot has been tested in two laboratories. Mean, SD, CV%, TAE, %Bias, z-score and
      sigma calculations were done. The medical method decision charts were created for
      all lots based upon normalized operational specifications which showed excellent
      precision in both control levels. Number of rejections in the study was nil.
      CONCLUSION: The extended use of controls is validated.

PMID- 28757823
TI  - Anesthesia for video-assisted thoracic surgery: An algorithm.

PMID- 28757825
TI  - Sternomental distance and sternomental displacement as predictors of difficult
      laryngoscopy and intubation in adult patients.
AB  - BACKGROUND: Several morphometric airway measurements have been used to predict
      difficult laryngoscopy (DL). This study evaluated sternomental distance (SMD) and
      sternomental displacement (SMDD, difference between SMD measured in neutral and
      extended head position), as predictors of DL and difficult intubation (DI).
      MATERIALS AND METHODS: We studied 610 adult patients scheduled to receive general
      anesthesia with tracheal intubation. SMD, SMDD, physical, and airway
      characteristics were measured. DL (Cormack-Lehane grade 3/4) and DI (assessed by
      Intubation Difficulty Scale) were evaluated. The optimal cut-off points for SMD
      and SMDD were identified by using receiver operating characteristic (ROC)
      analysis. Multivariate logistic regression was used to predict DL and ROC curve
      was used to assess accuracy on developed regression model. RESULTS: The incidence
      of DL and DI was 15.4% and 8.3%, respectively. The cut-off values for SMD and
      SMDD were <=14.75 cm (sensitivity 66%, specificity 60%) and <=5.25 cm
      (sensitivity 70%, specificity 53%), respectively, for predicting DL. The area
      under the curve (AUC) with 95% confidence interval (CI) for SMD was 0.66 (0.60
      0.72) and that for SMDD was 0.687 (0.63-0.74). Multivariate analysis with
      logistic regression identified inter-incisor distance, neck movement <80 degrees
      , SMD, SMDD, short neck and history of snoring as predictors and the predictive
      model so obtained exhibited a higher diagnostic accuracy (AUC: 0.82; 95% CI 0.77
      0.86). SMDD, but not SMD, correlated with DI. CONCLUSIONS: Both SMD and SMDD
      provide a rapid, simple, objective test that may help identifying patients at
      risk of DL. Their predictive value improves considerably when combined with the
      other predictors identified by logistic regression.

PMID- 28757824
TI  - Effects of preincisional analgesia with surgical site infiltration of ketamine or
      levobupivacaine in patients undergoing abdominal hysterectomy under general
      anesthesia; A randomized double blind study.
AB  - CONTEXT: Postoperative pain management remains a cornerstone in patient's
      management to ensure a better quality of life. Preemptive analgesia is reported
      to inhibit the persistence of postoperative pain. AIMS: The aim of this study is
      to assess the analgesic effectiveness of preincisional infiltration of ketamine
      following elective abdominal hysterectomy as compared to levobupivacaine.
      SETTINGS AND DESIGN: This was a prospective, randomized, double-blind study.
      SUBJECTS AND METHODS: This study included 48 patients undergoing abdominal
      hysterectomy under general anesthesia. They were randomized into two equal
      groups; Group K received subcutaneous infiltration of 20 ml containing ketamine 2
      mg/kg and Group L received subcutaneous infiltration of 20 ml of levobupivacaine
      0.25% along the Pfannenstiel incision 5 min before incision. Postoperative pain
      was assessed using visual analog scale (VAS) at rest and on coughing with
      evaluation of additional opioid analgesic requirements. STATISTICAL ANALYSIS
      USED: Numerical variables were presented as mean and standard deviation or median
      and range as appropriate. The intergroup differences were compared using the
      independent-sample Student's t-test or Mann-Whitney test for numerical variables.
      RESULTS: VAS score decreased significantly in Group L from 10 to 24 h and in
      Group K from 8 to 24 h as compared to the immediate postoperative reading. VAS
      score in ketamine group was significantly lower than that in the levobupivacaine
      group 8, 10, and 24 h postoperatively. Ketamine group showed delayed request of
      additional opioid analgesia (P < 0.001) with significantly less opioid
      consumption (P < 0.001) as compared to levobupivacaine. The total dose of
      meperidine consumed during the 24 postoperative h was significantly smaller in
      ketamine group (P < 0.001). CONCLUSION: Surgical site infiltration of ketamine is
      a promising preemptive analgesic method in the lower abdominal surgery with
      minimal sedation and adverse effects.

PMID- 28757826
TI  - An observational study: Effects of tenting of the abdominal wall on peak airway
      pressure in robotic radical prostatectomy surgery.
AB  - BACKGROUND: Robotic radical prostatectomy (RRP) is associated with various
      anesthetic challenges due to pneumoperitoneum and deep Trendelenburg position.
      Tenting of the abdominal wall done in RRP surgery causes decrease in peak airway
      pressure leading to better ventilation. Herein, we aimed to describe the effects
      of tenting of the abdominal wall on peak airway pressure in RRP surgery performed
      in deep Trendelenburg position. METHODS: One hundred patients admitted for RRP in
      Kokilaben Dhirubhai Ambani Hospital of American Society of Anesthesiologists 1
      and 2 physical status were included in the study. After undergoing preanesthesia
      work-up, patients received general anesthesia. Peak airway pressures were
      recorded after induction of general anesthesia, after insufflation of CO2, after
      giving Trendelenburg position, and after tenting of the abdominal wall with
      robotic arms. RESULTS: Mean peak airway pressure recording after induction in
      supine position was 19.5 +/- 2.3 cm of H2O, after insufflation of CO2 in supine
      position was 26.3 +/- 2.6 cm of H2O, after giving steep head low was 34.1 +/- 3.4
      cm of H2O, and after tenting of the abdominal wall with robotic arms was 29.5 +/-
      2.5 cm of H2O. P value is highly statistically significant (P = 0.001).
      CONCLUSION: Tenting of the abdominal wall during RRP is beneficial as it
      decreases peak airway pressure and helps in better ventilation and thus reduces
      the ill effects of raised peak airway pressure and intra-abdominal pressures.

PMID- 28757827
TI  - Digital assistance of nasogastric tube insertion in intubated patients under
      general anesthesia: A single-blinded prospective randomized study.
AB  - BACKGROUND: Nasogastric tube (NGT) insertion may pose a special problem in
      patients under general anesthesia with first attempt failure rates up to 50%. To
      increase insertion success rate and decreases related complications, several
      techniques have been developed. In this study, digital assistance technique is
      compared to the classic insertion technique in neck flexion. MATERIALS AND
      METHODS: In this prospective randomized study, 160 patients were randomly
      allocated into two groups; control group (Group C, n = 80) where NGT tube will be
      inserted with the neck in flexion position and digital facilitation group (Group
      D, n = 80). RESULTS: Overall success rate and first attempt success were
      statistically higher in Group D compared to Group C (94% vs. 81%, P = 0.02, 80%
      vs. 62%, P = 0.01 respectively) with significantly lower insertion time in Group
      D (13 +/- 5 s. vs. 10 +/- 3 s., P = 0.00). CONCLUSIONS: Digital assistance of NGT
      insertion in the anesthetized or unconscious patient is an effective, fast, and
      safe method that can be either used as a routine technique or as a rescue in case
      of failed other methods.

PMID- 28757828
TI  - Comparison of infracondylar versus subsartorial approach to saphenous nerve
      block: A randomized controlled study.
AB  - BACKGROUND AND OBJECTIVES: Only a few different approaches are currently utilized
      for saphenous nerve block. Our study aimed to compare two different ultrasound
      (US)-guided saphenous nerve blocks and designed this study to test the hypothesis
      that the medial infracondylar approach has more success rate than the
      subsartorial approach applied in saphenous nerve blockage. METHODS: The study
      included 76 patients (18-65 years old) with the American Society of
      Anesthesiologists physical status of I-III, who were scheduled for below-knee
      surgery by the orthopedics clinic. The patients who underwent US-guided saphenous
      nerve blockade were randomly divided into two groups: Group S (subsartorial
      approach) and Group M (medial infracondylar approach). For all patients who had a
      block procedure, the pinprick test was performed using a blunt needle on the
      saphenous nerve dermatome. Success rate, time of block performance (TBP), onset
      time of block (OTB), and duration of sensory blockade (DSB) were recorded using a
      patient follow-up form. RESULTS: The US-guided saphenous nerve block success rate
      was similar (88% vs. 91%) or both techniques. The DSB values were 415.2 +/- 65.3
      min (95% confidence interval [CI]: 286.3-539.8) for Group S and 369.7 +/- 52.2
      min (95% CI: 265.6-467.8) for Group M (P = 0.04), and no significant differences
      in the TBP and OTB were observed between the groups. CONCLUSION: Both of the
      different anatomical approaches have equally high success rates. Although the DSB
      was found to be significantly longer in the subsartorial approach, this is
      clinically unimportant, and the medial infracondylar approach is still a viable
      alternative technique during saphenous nerve blockage.

PMID- 28757829
TI  - Effect of dexmedetomidine as an adjuvant to bupivacaine in femoral nerve block
      for perioperative analgesia in patients undergoing total knee replacement
      arthroplasty: A dose-response study.
AB  - CONTEXT: Dexmedetomidine is being increasingly used in nerve blocks. However,
      there are only a few dose determination studies. AIMS: To compare two doses of
      dexmedetomidine, in femoral nerve block, for postoperative analgesia after total
      knee arthroplasty (TKA). SETTINGS AND DESIGN: A prospective, randomized,
      controlled trial was conducted in the Department of Anesthesia at AIIMS, a
      Tertiary Care Hospital. MATERIALS AND METHODS: Sixty American Society of
      Anesthesiologists I-II patients undergoing TKA under subarachnoid block were
      randomized to three Groups A, B, and C. Control Group A received 20 ml (0.25%) of
      bupivacaine in femoral nerve block. Groups B and C received 1 and 2 MUg/kg
      dexmedetomidine along with bupivacaine for the block, respectively. Outcomes
      measured were analgesic efficacy measured in terms of visual analog scale (VAS)
      score at rest and passive motion, duration of postoperative analgesia, and
      postoperative morphine consumption. Adverse effects of dexmedetomidine were also
      studied. STATISTICAL ANALYSIS USED: All qualitative data were analyzed using Chi
      square test and VAS scores using Kruskal-Wallis test. Comparison of patient
      controlled analgesia (PCA) morphine consumption and time to first use of PCA were
      done using ANOVA followed by Least Significant Difference test. A P < 0.05 was
      considered statistically significant. RESULTS: The VAS score at rest was
      significantly lower in Group C compared to Groups A and B (P < 0.05). There was
      no difference in VAS score at motion between Groups B and C. The mean duration of
      analgesia was significantly longer in Group C (6.66 h) compared to Groups A (4.55
      h) and B (5.70 h). Postoperative mean morphine consumption was significantly
      lower in Group C (22.85 mg) compared to Group A (32.15 mg) but was comparable to
      Group B (27.05 mg). There was no significant difference in adverse effects
      between the groups. CONCLUSION: The use of dexmedetomidine at 2 MUg/kg dose in
      femoral nerve block is superior to 1 MUg/kg for providing analgesia after TKA,
      although its role in facilitating early ambulation needs further evaluation.

PMID- 28757830
TI  - A feasibility study to assess vallecula and pyriform sinus using protocol-based
      ultrasonic evaluation of floor of mouth and upper airway.
AB  - PURPOSE: The current study aimed to systematically evaluate the sonoanatomy of
      floor of the mouth and upper airway using protocol-based ultrasonography (USG);
      and to assess the feasibility of imaging the valleculae and pyriform fossae.
      MATERIALS AND METHODS: An institutional prospective observational study was
      planned on fifty volunteers of all ages and both sexes, attending outpatient
      department for nonairway-related diseases. Protocol for ultrasonographic systemic
      evaluation was designed before starting the trial. All the patients were
      positioned supine with neck extended (sniffing position), seven steps of
      ultrasonographic protocol were followed and visualization of structures denoted
      in each step was documented. Furthermore, time taken to complete each scan was
      noted. RESULTS: The USG was completed, and checklist successfully followed in all
      cases. Floor of mouth structures was easy to evaluate and visualized with ease in
      all the cases. Epiglottis was visualized in 100% cases in transverse plane.
      Valleculae and pyriform fossae were identified in 82% and 90% of the cases,
      respectively, and they appeared either as paired air-filled round structures or
      air-lined linear structures. Complete visualization of vocal cords was seen in
      78% females and 63% males. The average time taken to complete the protocol-based
      study was 10.4 +/- 1.4 min. CONCLUSIONS: Application of protocol-based USG for
      upper airway can allow the examination of structures from tongue to thyroid
      cartilage in a thorough, convenient, and timely manner. The air filled/lined
      structures such as valleculae, pyriform fossae, and vocal cords can be visualized
      in majority of the cases.

PMID- 28757831
TI  - Cervical epidural puncture guided by fluoroscopy in comparison to acoustic
      signals: Clinical results.
AB  - BACKGROUND AND AIM: The increasing cases of the cervical epidural but the
      practitioners in need for a new method to decrease the safety of the injection
      and to improve the learning curve of the trainee. Furthermore, it should replace
      the potentially hazards, conventional one, which is the fluoroscope. Acoustic
      signals were tested for this purpose. METHODS: Thirty-two patients were assigned
      to have a cervical epidural for pain management using both acoustic signals and
      fluoroscopy simultaneously. RESULTS: The incidence of success was 100% with no
      complications. Likewise, the decrease in fluoroscopy shots number was 70%.
      CONCLUSIONS: Acoustic signals are a simple, effective method of cervical epidural
      insertion. It reduces the usage of fluoroscopy and can be used as a learning
      tool.

PMID- 28757832
TI  - Sugammadex versus two doses of neostigmine for reversal of rocuronium in gastric
      sleeve surgery.
AB  - BACKGROUND AND AIM: The aim of this prospective randomized trial is to compare
      the quality of reversal of rocuronium with either sugammadex (SUG) versus 2.5 mg
      or 5 mg neostigmine (NEO). PATIENTS AND METHODS: A total of 110 patients with
      body mass index >40 underwent elective gastric sleeve surgery were enrolled in
      this study. Exclusion criteria included patients with co-existing muscular and
      cardiovascular diseases. Patients were randomly allocated to one of the following
      groups: group A (SUG), Group B (NEO 2.5 mg), and Group C (NEO 5 mg). General
      anesthesia was induced in the three groups using propofol 2.0 mg/kg of corrected
      body weight (CBW) and fentanyl 3 mcg/kg of CBW. Anesthesia was maintained with
      O2/air/desflurane 1 minimum alveolar concentration. Remifentanil infusion started
      at 0.05-0.2 mcg/kg/min. Tracheal intubation was facilitated with rocuronium 1.2
      mg/kg of CBW guided with PNS. When the train of four (TOF) reached zero,
      intubation was performed using a GlideScope. At the end of surgery, TOF ratio and
      posttetanic counts were recorded. SUG 2 mg/kg of CBW (Group A), NEO 2.5 mg (Group
      B), and NEO 5 mg (Group C) were administered according to the random envelope.
      The time to achieve 90% of TOF was recorded in seconds using a timer. ANOVA for
      repeated measurements was used for statistical analyses. P <0.05 was considered
      statistically significant. RESULTS: There was a positive correlation (P < 0.05)
      between the duration of surgery and the time to reach 90% of TOF in all the three
      groups. The time to reach 90% TOF was significantly shorter with Group A versus
      Groups B and C (P < 0.05). CONCLUSION: Although SUG proved to be faster than NEO
      5 mg in attaining TOF >90%, the recovery pattern of both was similar.

PMID- 28757833
TI  - Using fentanyl and propofol for tracheal intubation during sevoflurane induction
      without muscle relaxants in children: A randomized prospective study.
AB  - CONTEXT: Tracheal intubation is frequently facilitated with sevoflurane induction
      without the use of muscle relaxants in children. AIM: The aim of this study was
      to compare the effects of two different doses of propofol preceded by a fixed
      dose of fentanyl during sevoflurane induction on quality of tracheal intubation
      in children. SETTINGS AND DESIGN: This was a prospective randomized study.
      SUBJECTS AND METHODS: Ninety American Society of Anesthesiologists I-II children
      aged 2-6 years were randomly assigned to one of two equal groups to receive 2
      MUg/kg of fentanyl with 2 mg/kg of propofol (Group I) or 2 MUg/kg of fentanyl
      with 3 mg/kg of propofol (Group II) during sevoflurane induction. The intubating
      conditions and hemodynamic responses were evaluated. The time from sevoflurane
      induction to loss of consciousness, to intravenous line insertion, and to
      intubation was measured. The occurrence of any adverse effect was recorded.
      STATISTICAL ANALYSIS USED: Results were analyzed using Student's t-test, paired t
      test, and Chi-square test. P < 0.05 was considered statistically significant.
      RESULTS: The incidence of excellent intubating conditions was achieved more
      significantly in Group II (41/45 patients, 91%) than that in Group I (31/45
      patients, 69%) (P = 0.008) (95% confidence interval [CI] =0.39-0.8). Whereas,
      there were no significant differences between the two groups in terms of the
      overall acceptable intubating conditions in Group I (40/45 patients, 89%) and
      Group II (43/45 patients, 96%) (P = 0.81) (95% CI = 0.71-1.31). No patient
      developed any adverse effect. CONCLUSION: The administration of 3 mg/kg propofol
      preceded by 2 MUg/kg fentanyl provided a higher proportion of excellent
      intubating conditions compared with 2 mg/kg propofol preceded by 2 MUg/kg
      fentanyl during sevoflurane induction in children without muscle relaxants.

PMID- 28757835
TI  - Pain relief following thoracic surgical procedures: A literature review of the
      uncommon techniques.
AB  - Thoracic surgical procedures can be either thoracotomy or thoracoscopy. In
      thoracotomy, the incision could be either muscle-cutting or muscle-sparing
      incision. The posterolateral thoracotomy incision is used for most general
      thoracic surgical procedures. This incision, which involves division of the
      latissimus dorsi and serratus anterior muscles, affords excellent exposure of the
      thoracic cavity. However, it is associated with significant morbidity, including
      impaired pulmonary function, postoperative chest pain, and restricted arm and
      shoulder movement. Various muscle-sparing incisions have been proposed to
      decrease the morbidity. Postthoracotomy pain originates from pleural and muscular
      damage, costovertebral joint disruption, and intercostal nerve damage during
      surgery. Inadequate pain relief after surgery affects the quality of patient's
      recovery and exposes the patients to postoperative morbidities. There is a
      tendency nowadays among thoracic surgeons and anesthesiologists toward the area
      of enhanced recovery after thoracic surgery which requires careful titration of
      the anesthetic drugs in awake patients undergoing thoracoscopic procedures. There
      is a common feeling among thoracic anesthesiologists that potthoracoscopy
      procedures produce less pain intensity versus thoracotomy which is partially
      true. However, effective management of acute pain following either
      thoracotomy/thoracoscopy is needed and may prevent these complications and reduce
      the likelihood of developing chronic pain. In this report, we are going to review
      the newly introduced postthoracotomy/thoracoscopy pain relief modalities with
      special reference to the new tendency of awake thoracic surgical procedures and
      its impact on enhanced recovery after surgery.

PMID- 28757834
TI  - Anesthesia for minimally invasive chest wall reconstructive surgeries: Our
      experience and review of literature.
AB  - Minimal access procedures have revolutionized the field of surgery and opened
      newer challenges for the anesthesiologists. Pectus carinatum or pigeon chest is
      an uncommon chest wall deformity characterized by a protruding breast bone
      (sternum) and ribs caused by an overgrowth of the costal cartilages. It can cause
      a multitude of problems, including severe pain from an intercostal neuropathy,
      respiratory dysfunction, and psychologic issues from the cosmetic disfigurement.
      Pulmonary function indices, namely, forced expiratory volume over 1 s, forced
      vital capacity, vital capacity, and total lung capacity are markedly compromised
      in pectus excavatum. Earlier, open surgical correction in the form of the Ravitch
      procedure was followed. Currently, in the era of minimally invasive surgery, Nuss
      technique (pectus bar procedure) is a promising step in chest wall reconstructive
      surgery for pectus excavatum. Reverse Nuss is a corrective, minimally invasive
      surgery for pectus carinatum chest deformity. A tailor-made anesthetic technique
      for this new procedure has been described here based on the authors' personal
      experience and thorough review of literature based on Medline, Embase, and Scopus
      databases search.

PMID- 28757836
TI  - Prebronchoplasty ventilation maneuver: Steering the outcome in the management of
      bronchial injuries!
AB  - Bronchial injuries are infrequently seen following blunt chest trauma and mostly
      have subtle clinical presentation. Its diagnosis is challenging and may be
      delayed resulting in myriad complications such as secondary infection,
      bronchiectasis, atelectasis, collapse, and fibrosis. We discuss the anesthetic
      management of a case of complete right principle bronchus transection with distal
      lung collapse, posted for surgical repair and highlight the unique intraoperative
      ventilation maneuver to identify the functional lung segment. This unique yet
      less recognized ventilation maneuver of the collapsed lung segment was performed
      just before bronchoplasty. The aforesaid maneuver may act as a pointer for
      further surgical course and a useful diagnostic and therapeutic modality in
      ensuring the eventual outcome in this subset of patients.

PMID- 28757837
TI  - Hypoxic hepatitis during the perioperative period in patients with severe
      pulmonary disease and cor pulmonale.
AB  - Hypoxic hepatitis (HH) is characterized by marked and transient elevations in
      liver enzyme levels in the absence of other potential causes of liver injury.
      Although rare, it can occur in the presence of hemodynamic instability and
      hypoxemia in patients with cor pulmonale. We report two cases of perioperative HH
      in patients with severe pulmonary disease and cor pulmonale. The first case is of
      a patient with cor pulmonale who underwent hemiarthroplasty for a femur fracture.
      Transient hypotension developed during spinal anesthesia and severe hypoxemia
      were observed in the postoperative period. After surgery, aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) levels suddenly
      increased to 3740 and 817 U/L, respectively. The second case is of a patient with
      congestive heart failure and cor pulmonale whose blood pressure and oxygen
      saturation decreased during induction of general anesthesia and after surgery,
      and AST, ALT, and lactic dehydrogenase levels increased to 1291, 1292, and 2710
      U/L, respectively. The liver enzyme levels normalized within 7-14 days in both
      cases. We speculate the diagnosis of these cases as HH.

PMID- 28757838
TI  - Anesthetic management for lobectomy of a 2-month-old infant with bronchogenic
      cyst: Case report along with review of literature.
AB  - Bronchogenic cyst, a benign congenital cystic lesion of the lung, is a rare cause
      of respiratory distress in children comprising 7.5% of all mediastinal masses. A
      thorough preoperative evaluation is crucial to plan for definitive intra- and
      post-operative management. All patients should be thoroughly evaluated for the
      presence of compression, deviation or distortion of airways and great veins. The
      easiest means of providing one lung ventilation in pediatrics is to intubate the
      main stem bronchus of the nonoperated lung. Other options available for pediatric
      one lung ventilation are single lumen endobronchial tubes, micro cuff tubes,
      Marraro bilumen tubes, and bronchial blockers. We hereby present a case report of
      a 2-month-old infant posted for excision of bronchogenic cyst along with a review
      of literature.

PMID- 28757839
TI  - Epidural for high-dose radiation brachytherapy in a noncompliant, super-obese
      patient with severe pulmonary hypertension.
AB  - High-dose radiation brachytherapy is a treatment for inoperable cervical and
      endometrial carcinoma. A general anesthetic is often utilized for patient
      comfort, facilitating patient transport to imaging resources, and allowing rapid
      discharge home after the procedure. Patient comorbidities, however, must be
      considered for every anesthetic performed. We describe a successful surgical
      epidural anesthetic for a patient with challenging comorbidities, including
      cardiac, pulmonary, and hematologic body systems.

PMID- 28757840
TI  - Learning impact of interactive video in anesthesiology residency training:
      Preliminary study with TED-Ed platform.

PMID- 28757841
TI  - Delayed tracheal perforation, a rare but dreaded complication of thyroidectomy.

PMID- 28757842
TI  - Anesthetic management in ABO incompatible kidney transplant.

PMID- 28757843
TI  - Scoliosis correction in an adolescent patient with Dandy-Walker syndrome: A case
      report.

PMID- 28757844
TI  - Worried about unintentional operation table movement? Here is an easy solution!!

PMID- 28757845
TI  - Intubating laryngeal mask airway as a conduit for fiberoptic bronchoscope: A safe
      and easy technique for intubation in prone position.

PMID- 28757846
TI  - Intraoperative seizures during redo cranioplasty for sinking skin flap syndrome-
      Role of BISTM monitor in detection.

PMID- 28757847
TI  - Accidental insertion of Ryle's tube in the airway in an intubated patient causing
      ventilator malfunction.

PMID- 28757848
TI  - Transnasal sphenopalatine ganglion block for the treatment of postdural puncture
      headache following spinal anesthesia.

PMID- 28757849
TI  - Inhaled nitric oxide, methemoglobinemia, and route of delivery.

PMID- 28757850
TI  - Anesthetic considerations in a patient with multiple system atrophy-cerebellar
      for lower limb surgery.

PMID- 28757851
TI  - Retrograde placement of spinal cord stimulator leads for treating resistant
      pelvic pain.

PMID- 28757852
TI  - Use of stylet in armored tube for nasotracheal intubation: Why not??

PMID- 28757853
TI  - Ultrasound-guided adductor and sciatic nerve block: Two in one approach at mid
      thigh level.

PMID- 28757854
TI  - Vocal cord dysfunction: Ultrasonography-aided diagnosis during routine airway
      examination.

PMID- 28757855
TI  - Ultrasound-guided stellate ganglion block for resistant ventricular tachycardia.

PMID- 28757856
TI  - Transverse approach for ultrasound-guided superior laryngeal nerve block for
      awake fiberoptic intubation.

PMID- 28757857
TI  - Intravenous mishap following residual anesthetic drug in intravenous extension
      line.

PMID- 28757858
TI  - Ultrasound-guided penile nerve block in pediatrics: An answer to intraoperative
      priapism.

PMID- 28757859
TI  - Erratum: What is the exact predictive role of preoperative white blood cell count
      for new-onset atrial fibrillation following open heart surgery?
AB  - [This corrects the article on p. 40 in vol. 7, PMID: 23717231.].

PMID- 28757860
TI  - Erratum: N-acetylcysteine instead of theophylline in patients with COPD who are
      candidates for elective off-pump CABG surgery: Is it possible in cardiovascular
      surgery unit?
AB  - [This corrects the article on p. 151 in vol. 7, PMID: 23956714.].

PMID- 28757861
TI  - Erratum: Preoperative C-reactive protein can predict early clinical outcomes
      following elective off-pump CABG surgery in patients with severe left ventricle
      dysfunction.
AB  - [This corrects the article on p. 327 in vol. 6, PMID: 23493333.].

PMID- 28757862
TI  - Proteogenomic Review of the Changes in Primate apoC-I during Evolution.
AB  - Apolipoprotein C-I has evolved more rapidly than any of the other soluble
      apolipoproteins. During the course of primate evolution, the gene for this
      apolipoprotein was duplicated. Prompted by our observation that the two resulting
      genes encode two distinct forms of apoC-I in great apes, we have reviewed both
      the genomic and proteomic data to examine what changes have occurred during the
      course of primate evolution. We have found data showing that one of the
      duplicated genes, known to be a pseudogene in humans, was also a pseudogene in
      Denisovans and Neandertals. Using genomic and proteomic data for primates, we
      will provide in this review evidence that the duplication took place after the
      divergence of New World monkeys from the human lineage and that the formation of
      the pseudogene took place after the divergence of the bonobos and chimpanzees
      from the human lineage.

PMID- 28757863
TI  - Automatic Image-Based Plant Disease Severity Estimation Using Deep Learning.
AB  - Automatic and accurate estimation of disease severity is essential for food
      security, disease management, and yield loss prediction. Deep learning, the
      latest breakthrough in computer vision, is promising for fine-grained disease
      severity classification, as the method avoids the labor-intensive feature
      engineering and threshold-based segmentation. Using the apple black rot images in
      the PlantVillage dataset, which are further annotated by botanists with four
      severity stages as ground truth, a series of deep convolutional neural networks
      are trained to diagnose the severity of the disease. The performances of shallow
      networks trained from scratch and deep models fine-tuned by transfer learning are
      evaluated systemically in this paper. The best model is the deep VGG16 model
      trained with transfer learning, which yields an overall accuracy of 90.4% on the
      hold-out test set. The proposed deep learning model may have great potential in
      disease control for modern agriculture.

PMID- 28757864
TI  - Dorsoventral and Proximodistal Hippocampal Processing Account for the Influences
      of Sleep and Context on Memory (Re)consolidation: A Connectionist Model.
AB  - The context in which learning occurs is sufficient to reconsolidate stored
      memories and neuronal reactivation may be crucial to memory consolidation during
      sleep. The mechanisms of context-dependent and sleep-dependent memory
      (re)consolidation are unknown but involve the hippocampus. We simulated memory
      (re)consolidation using a connectionist model of the hippocampus that explicitly
      accounted for its dorsoventral organization and for CA1 proximodistal processing.
      Replicating human and rodent (re)consolidation studies yielded the following
      results. (1) Semantic overlap between memory items and extraneous learning was
      necessary to explain experimental data and depended crucially on the recurrent
      networks of dorsal but not ventral CA3. (2) Stimulus-free, sleep-induced internal
      reactivations of memory patterns produced heterogeneous recruitment of memory
      items and protected memories from subsequent interference. These simulations
      further suggested that the decrease in memory resilience when subjects were not
      allowed to sleep following learning was primarily due to extraneous learning. (3)
      Partial exposure to the learning context during simulated sleep (i.e., targeted
      memory reactivation) uniformly increased memory item reactivation and enhanced
      subsequent recall. Altogether, these results show that the dorsoventral and
      proximodistal organization of the hippocampus may be important components of the
      neural mechanisms for context-based and sleep-based memory (re)consolidations.

PMID- 28757865
TI  - Emergency Backwards Whipple for Bleeding: Formidable and Definitive Surgery.
AB  - INTRODUCTION: During the past decades, the safety of pancreatoduodenectomy has
      improved, with low mortality and reduced morbidity, particularly in centers with
      extensive experience. Emergency pancreatoduodenectomy is an uncommon event, for
      treatment of pancreaticoduodenal trauma, bleeding, or perforation. We herein
      present a single center experience concerning nontrauma emergency
      pancreatoduodenectomy for pancreaticoduodenal bleeding. METHODS: From January
      2007 to December 2015, from a population of 134 PD (70 males and 64 females, mean
      age 62.2, range 34-82), 5 patients (3.7%; 2 males and 3 females, mean age 64,
      range 57-70) underwent one-stage emergency pancreatoduodenectomy for
      uncontrollable nontrauma pancreaticoduodenal bleeding in our tertiary center.
      RESULTS: All the 5 patients underwent a backwards Whipple with a morbidity of 60%
      and a mortality of 20% (1/5). The other 4 patients were recovered and discharged
      with a median postoperative length of stay of 17 days (range 14-23). CONCLUSION:
      Emergency pancreatoduodenectomy is a definitive life-saving procedure allowing
      for a rapid control of bleeding when other less invasive approaches
      (transcatheter arterial embolization or interventional endoscopy) are exhausted,
      unavailable, or unsafe. It should be particularly considered in neoplastic
      disease and tailored by surgeons with a high level of experience in pancreatic
      surgery.

PMID- 28757866
TI  - Efficacy, Safety, and Overall Quality of Life of Endoscopic Submucosal Dissection
      for Early Colorectal Cancer in Elderly Patients.
AB  - PURPOSE: Studies reporting the treatment of early colorectal cancer (ECC) by
      endoscopic submucosal dissection (ESD) in elderly patients are lacking in China.
      The aim was to evaluate the efficacy, safety and overall quality of life of
      elderly patients with ECC who undergoing ESD. METHODS: Three hundred and seventy
      nine patients with 401 colorectal lesions entered into our study from March 2013
      to March 2016 (Patients with an age 70 years old or older were divided into the
      elderly group and those who were less than 70-year-old entered the non-elderly
      group). RESULTS: No significant differences were found in sex ratio, body mass
      index, location, endoscopic classification, pathological pattern, lesion size,
      mean procedure time, hospitalization days, complete excision, and en bloc
      resection rate between the two groups (P > 0.05). No significant differences were
      observed between the groups in terms of complications during and after ESD
      procedure (P > 0.05). There were no statistical differences between two groups in
      Quality of life index (QL-Index) and European Organization for Research and
      Treatment quality of life version 3.0 questionnaire (EORTC QLQ-C30) scores (P >
      0.05). CONCLUSION: ESD was relatively safe and effective for elderly patients
      with ECC, and it may be an recommended first-line treatment.

PMID- 28757867
TI  - Factors Related to Significant Improvement of Estimated Glomerular Filtration
      Rates in Chronic Hepatitis B Patients Receiving Telbivudine Therapy.
AB  - BACKGROUND AND AIM: The improvement of estimated glomerular filtration rates
      (eGFRs) in chronic hepatitis B (CHB) patients receiving telbivudine therapy is
      well known. The aim of this study was to clarify the kinetics of eGFRs and to
      identify the significant factors related to the improvement of eGFRs in
      telbivudine-treated CHB patients in a real-world setting. METHODS: Serial eGFRs
      were calculated every 3 months using the Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equation. The patients were classified as CKD-1, -2, or 
      3 according to a baseline eGFR of >=90, 60-89, or <60 mL/min/1.73 m2,
      respectively. A significant improvement of eGFR was defined as a more than 10%
      increase from the baseline. RESULTS: A total of 129 patients were enrolled, of
      whom 36% had significantly improved eGFRs. According to a multivariate analysis,
      diabetes mellitus (DM) (p = 0.028) and CKD-3 (p = 0.043) were both significantly
      related to such improvement. The rates of significant improvement of eGFR were
      about 73% and 77% in patients with DM and CKD-3, respectively. CONCLUSIONS:
      Telbivudine is an alternative drug of choice for the treatment of hepatitis B
      patients for whom renal safety is a concern, especially patients with DM and CKD
      3.

PMID- 28757868
TI  - 13C Methacetin Breath Test for Assessment of Microsomal Liver Function:
      Methodology and Clinical Application.
AB  - Assessment of the liver function, and the need of constant monitoring of the
      organ's capacity, concerns not only patients with primary liver diseases, but
      also those at risk of hepatopathies secondary to other chronic diseases. Most
      commonly, the diagnostics is based on measurements of static biochemical
      parameters, which allow us to draw conclusions only indirectly about the function
      and the degree of damage of the organ. On the other hand, liver biopsy is an
      invasive procedure and therefore it is associated with a considerable risk of
      complications. Dynamic tests enable us to assess quantitatively the organ's
      functional reserve by analyzing the kinetics of the metabolization of the
      substrate by the liver. In practice applied are breath tests using substances
      such as aminopyrine, caffeine, methacetin, erythromycin (for assessment of the
      microsomal function); phenylalanine, galactose (for assessment of the cytosolic
      function); methionine, octanoate, ketoisocaproic acid (for assessment of the
      mitochondrial function). The test with 13C methacetin belongs to the best
      described and most widely applied methods in noninvasive liver function
      assessment. Due to the rising availability of this method, knowledge concerning
      its limitations and controversies regarding the methodology, as well as its
      usefulness in chosen groups of patients, seems to be vital.

PMID- 28757869
TI  - Factors Associated with Postoperative Prolonged Mechanical Ventilation in
      Pediatric Liver Transplant Recipients.
AB  - INTRODUCTION: Almost all pediatric orthotopic liver transplant (OLT) recipients
      require mechanical ventilation in the early postoperative period. Prolonged
      postoperative mechanical ventilation (PPMV) may be a marker of severe disease and
      may be associated with morbidity and mortality. We determined the incidence and
      risk factors for PPMV in children who underwent OLT. METHODS: This was a
      retrospective analysis of data collected on 128 pediatric OLT recipients. PPMV
      was defined as postoperative ventilation >= 4 days. Perioperative characteristics
      were compared between cases and control groups. Multivariable logistic regression
      analysis was used to calculate odds ratios for PPMV after controlling for
      relevant cofactors. RESULTS: An estimated 25% (95% CI, 17.4%-32.6%) required
      PPMV. The overall incidence of PPMV varied significantly by age group with the
      highest incidence among infants. PPMV was associated with higher postoperative
      mortality (p = 0.004) and longer intensive care unit (p < 0.001) and hospital
      length of stay (p < 0.001). Multivariable analysis identified young patient age,
      preoperative hypocalcemia, and increasing duration of surgery as independent
      predictors of PPMV following OLT. CONCLUSION: The incidence of PPMV is high and
      it was associated with prolonged ICU and hospital LOS and higher posttransplant
      mortality. Surgery duration appears to be the only modifiable predictor of PPMV.

PMID- 28757871
TI  - Quantification of Barbatusin and 3beta-Hydroxy-3-deoxybarbatusin in Plectranthus
      Species by HPLC-DAD.
AB  - The concentration of diterpenes barbatusin (1) and 3beta-hydroxy-3
      deoxybarbatusin (2) in the extracts from leaves of Plectranthus grandis, P.
      barbatus, P. ornatus, and P. amboinicus was evaluated by HPLC-DAD analysis on a
      Luna C-18 column, using isocratic mixtures of water and acetonitrile as eluents.
      The regression equations were obtained with good linearity (r2 > 0.99) and limit
      of quantifications was higher than 0.1 ug/mL. The precision (lower than 3.5%,
      within day) and accuracy (higher than 81.7% and lower than 107.6%) of the methods
      were adequate. Barbatusin (1) was detected in P. grandis (15.432 +/- 2.28 mg/g)
      and P. barbatus (5.198 +/- 3.45 mg/g) extracts, while compound 2 was detected in
      P. grandis (4.068 +/- 3.34 mg/g), P. barbatus (0.654 +/- 5.86 mg/g), P.
      amboinicus (0.160 +/- 7.25 mg/g), and P. ornatus (0.763 +/- 5.10 mg/g). The
      evaluated validation parameters were satisfactorily achieved, and the developed
      methodology represents a suitable tool for application in the quantification of
      barbatusin (1) and 3beta-hydroxy-3-deoxybarbatusin (2) in Plectranthus species.

PMID- 28757870
TI  - Peripheral Exophytic Oral Lesions: A Clinical Decision Tree.
AB  - Diagnosis of peripheral oral exophytic lesions might be quite challenging. This
      review article aimed to introduce a decision tree for oral exophytic lesions
      according to their clinical features. General search engines and specialized
      databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct,
      Scopus, Embase, and authenticated textbooks were used to find relevant topics by
      means of keywords such as "oral soft tissue lesion," "oral tumor like lesion,"
      "oral mucosal enlargement," and "oral exophytic lesion." Related English-language
      articles published since 1988 to 2016 in both medical and dental journals were
      appraised. Upon compilation of data, peripheral oral exophytic lesions were
      categorized into two major groups according to their surface texture: smooth
      (mesenchymal or nonsquamous epithelium-originated) and rough (squamous epithelium
      originated). Lesions with smooth surface were also categorized into three
      subgroups according to their general frequency: reactive hyperplastic
      lesions/inflammatory hyperplasia, salivary gland lesions (nonneoplastic and
      neoplastic), and mesenchymal lesions (benign and malignant neoplasms). In
      addition, lesions with rough surface were summarized in six more common lesions.
      In total, 29 entities were organized in the form of a decision tree in order to
      help clinicians establish a logical diagnosis by a stepwise progression method.

PMID- 28757872
TI  - Production, Characterization, and Antimicrobial Activity of Mycocin Produced by
      Debaryomyces hansenii DSMZ70238.
AB  - The present study was conducted to estimate the antimicrobial activity and the
      potential biological control of the killer toxin produced by D. hansenii
      DSMZ70238 against several pathogenic microorganisms. In this study, the effects
      of NaCl, pH, and temperature, killer toxin production, and antimicrobial activity
      were studied. The results showed that the optimum inhibitory effect of killer
      toxin was at 8% NaCl, and the diameters of clear zones were 20, 22, 22, 21, 14,
      and 13 mm for Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae,
      Streptococcus pyogenes, Candida albicans, and Candida neoformans, respectively.
      The largest inhibition zones were observed at pH 4.5 with inhibition zone of 16,
      18, 17, 18, 11, and 12 mm for the same microorganisms. The results also showed
      that 25 degrees C is the optimal temperature for toxin killing activity against
      all targeted microorganisms. In addition, the activity of killer toxin
      significantly inhibited the growth of fungal mycelia for all target pathogenic
      fungi and the percentages of inhibition were 47.77, 48.88, 52.22, and 61.11% for
      Trichophyton rubrum, Alternaria alternata, Trichophyton concentricum, and
      Curvularia lunata, respectively. The results showed the highest growth rate of D.
      hansenii DSMZ70238 under condition of 8% NaCl concentration, pH 4.5, and 25
      degrees C for 72 h.

PMID- 28757873
TI  - Absence of Relationship between Mitochondrial DNA Haplogroups and Cisplatin
      Induced Hearing Loss.
AB  - BACKGROUND: Many drugs used for cancer chemotherapy produce reactive oxygen
      species, thus leading to various complications including nephrotoxicity,
      cardiotoxicity, and ototoxicity. OBJECTIVE: We have provided a haplogroup
      analysis of a cohort of cancer patients treated with chemotherapy and compared
      factors associated with associated hearing loss. STUDY DESIGN AND METHODS: This
      observational cohort study includes a pure-tone audiometry of the patients who
      underwent chemotherapeutic treatment. Medical history, presence of risk factors
      for hearing loss, toxic habits, and association with haplogroups have been
      determined. RESULTS: 40% of patients developed hearing loss after administration
      of cisplatin, which was bilateral and symmetrical and of high frequencies. The
      most frequent haplogroup was H with a slight overexpression of groups V and K and
      a low frequency of groups J and T. No association of the haplogroup types with
      the hearing loss has been found; however age was revealed as an important
      determining factor. CONCLUSIONS: Ototoxicity caused by cisplatin is manifested as
      bilateral, symmetrical, and predominantly high frequency hearing loss. Although
      we did not find a strong correlation of haplogroups with ototoxicity, our results
      revealed the existence of a risk group of elderly patients over 60, which are
      more susceptible to hearing loss induced by cisplatin, than young adults,
      regardless of preexisting hearing loss.

PMID- 28757874
TI  - A Rare Case of Primary Bilateral Adrenal Lymphoma.
AB  - Lymphoma may involve the adrenal glands, but primary lymphoma is rare. Only a few
      cases have been reported in medical literature. Primary adrenal lymphoma is
      extremely rare, accounting for <1% of non-Hodgkin lymphomas. We here present a
      case of a middle-aged female who presented with persistent fever for three weeks.
      She also reported significant weight loss of more than 10 kgs over the duration
      of three months. Computed tomography of the thorax and abdomen and pelvis
      demonstrated bilateral adrenal masses. She underwent short Synacthen test which
      showed evidence of adrenal insufficiency. She underwent CT-guided adrenal gland
      biopsy. Histology of adrenal gland biopsy showed features consistent with diffuse
      large B-cell lymphoma. She was started on R-CHOP chemotherapy and had a good
      clinical response and remained in complete remission for five months after
      chemotherapy.

PMID- 28757875
TI  - Acute Appendicitis: An Extracolonic Manifestation of Clostridium difficile
      Colitis.
AB  - The current report is the case of a 30-year-old male patient who presented with
      symptomatology suggestive of appendicitis. However, careful history-taking and
      laboratory tests led to the diagnosis of Clostridium difficile colitis, resulting
      in successful nonsurgical management of this patient. Although both appendicitis
      and C. difficile colitis are common conditions, they are rarely diagnosed
      concurrently. This is reflected by paucity of literature describing this
      manifestation. Given this current presentation, the authors contend that the
      manifestation of extracolonic colitis within the appendix is possibly
      underdiagnosed or misdiagnosed as an acute appendicitis and thus potentially
      results in unnecessary surgical intervention. This report reminds physicians to
      consider the medical approach to managing acute appendicitis given the
      possibility of underlying C. difficile colitis as the causative factor.

PMID- 28757876
TI  - A Case of Atopic Myelitis with Cervical Cavernous Angioma.
AB  - Atopic myelitis, a type of myelitis which appears in patients with elevated serum
      levels of immunoglobulin E (IgE), occurs more commonly in the cervical spinal
      cord, but this mechanism has not yet been elucidated. Herein, we experienced a
      case of atopic myelitis developed during the growth of cervical cavernous angioma
      caused by bleeding. A 37-year-old woman suffered from hand swelling caused by a
      house cat licking. At the same time when cavernous angioma had grown, she
      experienced a numbness in her four extremities, and multifocal peritumoral
      hyperintense spinal cord signals were seen. The diagnosis of atopic myelitis was
      made because we observed significantly elevated levels of specific IgE antibody
      to cat dander. Symptoms disappeared immediately after steroid pulse therapy. We
      subsequently resected a cavernous angioma, and eosinophil invasion was found
      inside it. This is the first case report of atopic myelitis which developed in
      association with spinal cord vascular lesions. A local blood-brain barrier
      breakdown due to hemorrhagic lesions of the spinal cord may have contributed to
      the onset of atopic myelitis.

PMID- 28757877
TI  - Trophic Activity and Phenotype of Adipose Tissue-Derived Mesenchymal Stem Cells
      as a Background of Their Regenerative Potential.
AB  - There has been an increased interest in mesenchymal stem cells from adipose
      tissue, due to their abundance and accessibility with no ethical concerns. Their
      multipotent properties make them appropriate for regenerative clinical
      applications. It has been shown that adipose-derived stem cells (ASCs) may differ
      between the origin sites. Moreover, a variety of internal and external factors
      may affect their biological characteristics, as what we aimed to highlight in
      this review. It has been demonstrated that ASCs secrete multiple trophic factors
      that are capable of stimulating cell proliferation and differentiation and
      migration of various cell types. Particular attention should be given to
      exosomes, since it is known that they contribute to the paracrine effects of
      MSCs. Secretion of trophic agents by ASCs is thought to be in a greater
      importance for regenerative medicine applications, rather than cells engraftment
      to the site of injury and their differentiation ability. The surface marker
      profile of ASCs seems to be similar to that of the mesenchymal stem cells from
      bone marrow, although some molecular differences are observed. Thus, in this
      review, we have attempted to define trophic activity, as well as phenotypic
      characterization of ASCs, as crucial factors for therapeutic usage.

PMID- 28757878
TI  - Neuroprotective Effects of Stem Cells in Ischemic Stroke.
AB  - Ischemic stroke, the most common subtype of stroke, has been one of the leading
      causes of mobility and mortality worldwide. However, it is still lacking of
      efficient agents. Stem cell therapy, with its vigorous advantages, has attracted
      researchers around the world. Numerous experimental researches in animal models
      of stroke have demonstrated the promising efficacy in treating ischemic stroke.
      The underlying mechanism involved antiapoptosis, anti-inflammation, promotion of
      angiogenesis and neurogenesis, formation of new neural cells and neuronal
      circuitry, antioxidation, and blood-brain barrier (BBB) protection. This review
      would focus on the types and neuroprotective actions of stem cells and its
      potential mechanisms for ischemic stroke.

PMID- 28757879
TI  - Mitochondrial Heterogeneity: Evaluating Mitochondrial Subpopulation Dynamics in
      Stem Cells.
AB  - Although traditionally viewed as the "powerhouse" of the cell, an accruing body
      of evidence in the rapidly growing field of mitochondrial biology supports
      additional roles of mitochondria as key participants in a multitude of cellular
      functions. While it has been well established that mitochondria in different
      tissues have distinctive ultrastructural features consistent with differential
      bioenergetic demands, recent and emerging technical advances in flow cytometry,
      imaging, and "-omics"-based bioinformatics have only just begun to explore the
      complex and divergent properties of mitochondria within tissues and cell types.
      Moreover, contemporary studies evaluating the role of mitochondria in pluripotent
      stem cells, cellular reprogramming, and differentiation point to a potential
      importance of mitochondrial subpopulations and heterogeneity in the field of stem
      cell biology. This review assesses the current literature regarding mitochondrial
      subpopulations within cell and tissue types and evaluates the current
      understanding of how mitochondrial diversity and heterogeneity might impact cell
      fate specification in pluripotent stem cells.

PMID- 28757880
TI  - Buccal Fat Pad as a Potential Source of Stem Cells for Bone Regeneration: A
      Literature Review.
AB  - Adipose tissues hold great promise in bone tissue engineering since they are
      available in large quantities as a waste material. The buccal fat pad (BFP) is a
      specialized adipose tissue that is easy to harvest and contains a rich blood
      supply, and its harvesting causes low complications for patients. This review
      focuses on the characteristics and osteogenic capability of stem cells derived
      from BFP as a valuable cell source for bone tissue engineering. An electronic
      search was performed on all in vitro and in vivo studies that used stem cells
      from BFP for the purpose of bone tissue engineering from 2010 until 2016. This
      review was organized according to the PRISMA statement. Adipose-derived stem
      cells derived from BFP (BFPSCs) were compared with adipose tissues from other
      parts of the body (AdSCs). Moreover, the osteogenic capability of
      dedifferentiated fat cells (DFAT) derived from BFP (BFP-DFAT) has been reported
      in comparison with BFPSCs. BFP is an easily accessible source of stem cells that
      can be obtained via the oral cavity without injury to the external body surface.
      Comparing BFPSCs with AdSCs indicated similar cell yield, morphology, and
      multilineage differentiation. However, BFPSCs proliferate faster and are more
      prone to producing colonies than AdSCs.

PMID- 28757881
TI  - Intrinsic Variability Present in Wharton's Jelly Mesenchymal Stem Cells and T
      Cell Responses May Impact Cell Therapy.
AB  - Wharton's jelly mesenchymal stem cells (WJ-MSC) exhibit immunomodulatory effects
      on T cell response. WJ-MSC are easy to collect, process, and proliferate rapidly
      in culture, but information on the variability of individual cell samples
      impacting upon in vitro expansion, immunomodulatory potential, and aging
      processes is still lacking. We propose to evaluate the immunomodulatory cytokine
      profile and capacity to inhibit T cell proliferation of WJ-MSC progressing to
      replicative senescence in order to analyze if expected responses are affected.
      Our results show that the gene expression of immunomodulatory molecules varied
      among samples with no specific pattern present. In coculture, all WJ-MSC were
      capable of inhibiting mitogen-activated CD3+ T cell proliferation, although to
      different degrees, and each PBMC responded with a different level of inhibition.
      Thus, we suggest that each WJ-MSC displays unique behavior, differing in patterns
      of cytokine mRNA expression and immunomodulatory capacity. We believe that
      variability between samples may play a role in the effectiveness of WJ-MSC
      employed therapeutically.

PMID- 28757882
TI  - Desktop Genetics.
AB  - Desktop Genetics is a bioinformatics company building a gene-editing platform for
      personalized medicine. The company works with scientists around the world to
      design and execute state-of-the-art clustered regularly interspaced short
      palindromic repeats (CRISPR) experiments. Desktop Genetics feeds the lessons
      learned about experimental intent, single-guide RNA design and data from
      international genomics projects into a novel CRISPR artificial intelligence
      system. We believe that machine learning techniques can transform this
      information into a cognitive therapeutic development tool that will revolutionize
      medicine.

PMID- 28757883
TI  - Emerging ethical perspectives in the clustered regularly interspaced short
      palindromic repeats genome-editing debate.
AB  - This paper provides an overview of the ethical issues in the international
      clustered regularly interspaced short palindromic repeats (CRISPR) genome editing
      debate from March 2015 to September 2016. We present the regulatory framework for
      embryo research in the UK, and explain why CRISPR is not a significant break with
      the past. We discuss the ethical issues arising from CRISPR applications beyond
      human embryos, namely the use of gene drive-engineered mosquitoes to eradicate
      diseases, engineering nonhuman animals to harvest organs for human transplant and
      engineering crops. We discuss the experiments that have demonstrated the
      technical feasibility of cultivating embryos in vitro for up to 14 days, and
      possibly beyond this limit, and the ethical issues arising from the proposal to
      extend the limit beyond 14 days.

PMID- 28757885
TI  - The next personalized medicine evolution in orthopedics: how diagnosing and
      treating scoliosis are about to change.

PMID- 28757884
TI  - The fuzzy world of precision medicine: deliberations of a precision medicine
      tumor board.
AB  - AIM: To understand how a cancer precision medicine tumor board (CPM-TB) made
      choices about return of results. MATERIALS & METHODS: Observed CPM-TB
      deliberations and completed in-depth interviews with committee members. RESULTS:
      Responding to complex evidence of ambiguous significance, deliberations of the
      CPM-TB were predicated on analytic validity and clinical utility. Members had
      concerns both about potential harms due to returning results based on weak
      evidence and about withholding potentially meaningful results. Group dynamics and
      the clinical experiences of individual committee members shaped their work.
      CONCLUSION: Both scientific evidence and the social context surrounding
      deliberations of a CPM-TB influenced decisions about return of results.
      Subjective elements, while present in any scientific endeavor, may carry more
      weight in the face of ambiguous findings.

PMID- 28757886
TI  - The influence of a gene-expression signature on the treatment of diagnostically
      challenging melanocytic lesions.
AB  - AIM: The effect of a gene-expression-based test on treatment of melanocytic
      neoplasms by dermatologists was evaluated. PATIENTS & METHODS: Pathologists
      submitted diagnostically challenging melanocytic neoplasms to a clinical
      laboratory for testing accompanied by pretest surveys documenting the intended
      treatment recommendations. The actual treatment rendered by dermatologists was
      then documented after testing. Changes between the pretest recommendations and
      actual treatment were analyzed. RESULTS: In 71.4% (55/77) of cases, there was a
      change from pretest recommendations to actual treatment. The majority of changes
      were consistent with the test result. There was an 80.5% (33/41) reduction in the
      number of biopsy site re-excisions performed for cases with a benign test result.
      CONCLUSION: The actual treatment of diagnostically challenging melanocytic
      neoplasms is influenced by the test.

PMID- 28757887
TI  - Traditional Chinese Medicine ShenZhuGuanXin Granules Mitigate Cardiac Dysfunction
      and Promote Myocardium Angiogenesis in Myocardial Infarction Rats by Upregulating
      PECAM-1/CD31 and VEGF Expression.
AB  - BACKGROUND: Myocardial infarction (MI) is the main cause of global mortality and
      morbidity despite the development of therapeutic approaches. ShenZhuGuanXin
      granules (SG) have been shown to possess cardioprotective effects against
      coronary heart disease (CHD). However, little is known about its specific
      mechanism. The present study aimed to investigate the therapeutic effect of SG in
      cardiac dysfunction and to demonstrate whether SG can promote myocardium
      angiogenesis by establishing a rat model of myocardial infarction with left
      anterior descending ligating. METHODS AND RESULTS: Three days after MI, rats were
      randomly divided into six groups: sham group (sham), MI group (MI), MI + low dose
      SG (SG-L) group, MI + middle dose SG (SG-M) group, MI + high dose SG (SG-H)
      group, and MI + compound Danshen dropping pills (CDDP) group as a positive
      control. Four weeks after administration, rats underwent hemodynamics and
      echocardiography study. Ventricle tissues were processed for histology and
      immunohistochemistry studies. Compared with MI group, SG treatment dose
      dependently improved cardiac hemodynamic function, attenuated infarct size,
      increased microvessel density, and increased the expression of PECAM-1/CD31 and
      VEGF. CONCLUSIONS: SG dose-dependently improved cardiac hemodynamic function and
      attenuated infarct size by promoting angiogenesis through upregulating PECAM
      1/CD31 and VEGF expression.

PMID- 28757888
TI  - Rhodiolae Kirliowii Radix et Rhizoma and Crataegus pinnatifida Fructus Extracts
      Effectively Inhibit BK Virus and JC Virus Infection of Host Cells.
AB  - The human polyomaviruses BK (BKPyV) and JC (JCPyV) are ubiquitous pathogens long
      associated with severe disease in immunocompromised individuals. BKPyV causes
      polyomavirus-associated nephropathy and hemorrhagic cystitis, whereas JCPyV is
      the causative agent of the fatal demyelinating disease progressive multifocal
      leukoencephalopathy. No effective therapies targeting these viruses are currently
      available. The goal of this study was to identify Chinese medicinal herbs with
      antiviral activity against BKPyV and JCPyV. We screened extracts of Chinese
      medicinal herbs for the ability to inhibit hemagglutination by BKPyV and JCPyV
      virus-like particles (VLPs) and the ability to inhibit BKPyV and JCPyV binding
      and infection of host cells. Two of the 40 herbal extracts screened, Rhodiolae
      Kirliowii Radix et Rhizoma and Crataegus pinnatifida Fructus, had
      hemagglutination inhibition activity on BKPyV and JCPyV VLPs and further
      inhibited infection of the cells by BKPyV and JCPyV, as evidenced by reduced
      expression of viral proteins in BKPyV-infected and JCPyV-infected cells after
      treatment with Rhodiolae Kirliowii Radix et Rhizoma or Crataegus pinnatifida
      Fructus extract. The results in this work show that both Rhodiolae Kirliowii
      Radix et Rhizoma and Crataegus pinnatifida Fructus may be sources of potential
      antiviral compounds for treating BKPyV and JCPyV infections.

PMID- 28757889
TI  - The Role of Rumination and Stressful Life Events in the Relationship between the
      Qi Stagnation Constitution and Depression in Women: A Moderated Mediation Model.
AB  - The qi stagnation constitution is associated with depression in traditional
      Chinese medicine. It is unclear how rumination and stressful life events affect
      the relationship between the qi stagnation constitution and depression. The Qi
      Stagnation Constitution Scale, Ruminative Response Scale, Center for
      Epidemiologic Studies Depression Scale, and Adolescent Self-Rating Life Events
      Checklist were used to assess this association in 1200 female college students.
      The results revealed that the qi stagnation constitution was positively
      associated with depression. Furthermore, rumination was a partial mediator of the
      relationship between the qi stagnation constitution and depression. In addition,
      stressful life events moderated the direct effect and mediating effect of the qi
      stagnation constitution on depression. These findings indicate that rumination
      and stressful life events may affect the relationship between the qi stagnation
      constitution and depression in women.

PMID- 28757890
TI  - In Vivo and In Vitro Hepatoprotective Effects of Geranium koreanum Methanolic
      Extract via Downregulation of MAPK/Caspase-3 Pathway.
AB  - Geranium koreanum (GK) is an indigenous Chinese herbal medicine widely used for
      the treatment of various inflammation and liver disorders. However, the exact
      mechanism of action of GK remains unknown. This study aimed to investigate the
      protective effect and related molecular mechanism of GK on NaAsO2-induced
      cytotoxicity in HepG2 cells and liver damage in mice. The cytoprotective role of
      GK was assessed on HepG2 cells using MTT assay. Oxidative stress and lactate
      dehydrogenase levels were measured with ROS and LDH assay. Histopathology and
      serum enzymes levels were estimated. The molecular mechanism was evaluated by
      qPCR and immunoblotting to ensure the hepatoprotective role of GK against NaAsO2
      intoxication in mice. We found cotreatment with GK significantly attenuated
      NaAsO2-induced cell viability loss, intracellular ROS, and LDH release. Hepatic
      histopathology and serum biochemical parameters, ALT, and AST were notably
      improved by cotreatment with GK. Beside, GK markedly altered both mRNA and
      protein expression level of MAPK. The proapoptotic and antiapoptotic protein
      Bax/Bcl-2 ratio was significantly regulated by GK. Moreover, GK remarkably
      suppressed the postapoptotic transcription protein cleaved caspase-3 expression.
      The present study reveals that GK possesses hepatoprotective activity which is
      probably involved in the modulation of the MAPK/caspase-3 pathway.

PMID- 28757891
TI  - Pharmacokinetics of Caffeic Acid, Ferulic Acid, Formononetin, Cryptotanshinone,
      and Tanshinone IIA after Oral Administration of Naoxintong Capsule in Rat by HPLC
      MS/MS.
AB  - Naoxintong capsule (NXTC) was a famous patent medicine of Traditional Chinese
      Medicine (TCM) to treat cerebrovascular diseases in China. An LC-MS/MS method was
      developed for simultaneous determination of 11 major ingredients (paeoniflorin,
      ecdysterone, amygdalin, mulberroside A, caffeic acid, ferulic acid, salvianolic
      acid B, astragaloside IV, formononetin, cryptotanshinone, and tanshinone IIA) in
      NXTC in rat plasma. All analytes were separated on an Eclipse plus C18 column
      using a gradient mobile phase system of acetonitrile-0.1% formic acid aqueous
      solution. The lower limits of quantification of 11 ingredients were between 0.075
      and 10 ng mL-1. The precision was less than 15% and the accuracies were between
      85% and 115%. The results showed that caffeic acid, ferulic acid, formononetin,
      cryptotanshinone, and tanshinone IIA could be detected after oral administration
      of NXTC. The validated method was successfully applied to pharmacokinetic study
      of the caffeic acid, ferulic acid, formononetin, cryptotanshinone, and tanshinone
      IIA in rats after oral administration of NXTC at single and triple dose.

PMID- 28757892
TI  - Maintaining Treatment Fidelity of Mindfulness-Based Relapse Prevention
      Intervention for Alcohol Dependence: A Randomized Controlled Trial Experience.
AB  - BACKGROUND: Treatment fidelity is essential to methodological rigor of clinical
      trials evaluating behavioral interventions such as Mindfulness Meditation (MM).
      However, procedures for monitoring and maintenance of treatment fidelity are
      inconsistently applied, limiting the strength of such research. OBJECTIVE: To
      describe the implementation and findings related to fidelity monitoring of the
      Mindfulness-Based Relapse Prevention for Alcohol Dependence (MBRP-A) intervention
      in a 26-week randomized controlled trial. METHODS: 123 alcohol dependent adults
      were randomly assigned to MM (MBRP-A and home practice, adjunctive to usual care;
      N = 64) or control (usual care alone; N = 59). Treatment fidelity assessment
      strategies recommended by the National Institutes of Health Behavior Change
      Consortium for study/intervention design, therapist training, intervention
      delivery, and treatment receipt and enactment were applied. RESULTS: Ten 8
      session interventions were delivered. Therapist adherence and competence,
      assessed using the modified MBRP Adherence and Competence Scale, were high. Among
      the MM group participants, 46 attended >=4 sessions; over 90% reported at-home MM
      practice at 8 weeks and 72% at 26 weeks. They also reported satisfaction with and
      usefulness of MM for maintaining sobriety. No adverse events were reported.
      CONCLUSIONS: A systematic approach to assessment of treatment fidelity in
      behavioral clinical trials allows determination of the degree of consistency
      between intended and actual delivery and receipt of intervention.

PMID- 28757893
TI  - Next-generation sequencing and norovirus.

PMID- 28757894
TI  - HIV-1 latent reservoir: size matters.
AB  - More than 35 million people remain infected with HIV-1. Upon antiretroviral
      therapy cessation, HIV-1-positive individuals systematically fail to achieve
      sustained virological remission, revealing the presence of a reservoir. This
      reservoir takes into account anatomical sanctuaries where HIV-1 continues to
      replicate, and latently infected cells also known as the latent reservoir (LR). A
      better understanding of the nature and features of the LR and its quantification
      are crucial to evaluate the efficiency of therapeutic strategies aiming at
      purging HIV-1. Culture- and PCR-based assays have already been implemented to
      measure the LR, and new assays are continuously being developed. In this review,
      we will discuss these methods highlighting the difficulties to accurately measure
      the LR, one main obstacle in curing HIV-1.

PMID- 28757895
TI  - Factors influencing mothers' decision to enroll their HIV-negative children in a
      hypothetical HIV vaccine trial.
AB  - : Despite advances in preventive treatments for HIV, children continue to become
      infected with HIV. Research has investigated adult and adolescents' willingness
      to participate in hypothetical HIV vaccine trials; however, maternal willingness
      to enroll their infants in such trials remains underexplored. AIM: This study
      explored the factors influencing mothers' decision-making about enrolling their
      HIV negative infants in a hypothetical HIV vaccine trial. Methods: HIV infected
      and uninfected mothers (n = 22) were interviewed. RESULTS: Several factors were
      identified as influencing the mothers' decisions, including perceptions and
      knowledge of HIV and vaccines. CONCLUSION: Maternal concerns about protecting
      their infants from HIV were also identified and mothers indicated that they were
      eager to vaccinate their children. Insufficient information and reassurance
      regarding vaccine trial safety and efficacy influenced maternal reluctance to
      enroll their child.

PMID- 28757896
TI  - The Role of Cultural Psychiatry in Improving the Policy Response to Central
      America's Unaccompanied Minors at the American Border: Local and Global
      Implications.
AB  - Since 2014, children from El Salvador, Guatemala, and Honduras unaccompanied by
      their parents have fled in large numbers to the United States to escape violent
      crime and social disadvantage. Current mental health policies in the U.S.
      government's response can be improved based on guidelines from professional
      psychiatric and psychological organizations. These guidelines emphasize the
      importance of immigration and culture, raising questions into how the field of
      cultural psychiatry can offer conceptual frameworks and methods to research
      unaccompanied minor migration as a humanitarian problem. This paper conducts a
      policy analysis by reviewing shortcomings in the U.S. response and explores the
      potential contributions of cultural psychiatrists in optimizing services to
      address the needs of these children in the U.S. and their countries of origin.

PMID- 28757897
TI  - A Qualitative Examination of Yoga for Middle School Adolescents.
AB  - The present study was part of a group randomized controlled trial in which 7th
      grade students were assigned to a yoga intervention or physical-education-as
      usual. Sixteen students were randomly selected from the yoga condition to
      participate in one-on-one interviews. Qualitative analyses revealed 13 themes
      that were organized into two categories: Usability (student perceptions of the
      usefulness, learnability, and convenience of the yoga intervention) and Effect
      (student perceptions of the direct results of the yoga intervention). Students
      reported both positive and negative opinions of yoga, especially when making
      direct comparisons between yoga and physical education. Students had particularly
      positive opinions regarding the beneficial effects of yoga on stress, sleep, and
      relaxation. Student opinions regarding the effects of yoga on self-regulation,
      social interaction, substance use, and academic performance were also generally
      positive, although somewhat mixed. Results suggest that qualitative research
      shows promise for providing an in-depth perspective on the impact of mind-body
      interventions in schools.

PMID- 28757898
TI  - Reverse Remodeling: Does This Work?

PMID- 28757899
TI  - Platinum nanoparticles: an exquisite tool to overcome radioresistance.
AB  - BACKGROUD: Small metallic nanoparticles are proposed as potential nanodrugs to
      optimize the performances of radiotherapy. This strategy, based on the enrichment
      of tumours with nanoparticles to amplify radiation effects in the tumour, aims at
      increasing the cytopathic effect in tumours while healthy tissue is preserved, an
      important challenge in radiotherapy. Another major cause of radiotherapy failure
      is the radioresistance of certain cancers. Surprisingly, the use of nanoparticles
      to overcome radioresistance has not, to the best of our knowledge, been
      extensively investigated. The mechanisms of radioresistance have been extensively
      studied using Deinococcus radiodurans, the most radioresistant organism ever
      reported, as a model. METHODS: In this work, we investigated the impact of ultra
      small platinum nanoparticles (1.7 nm) on this organism, including uptake,
      toxicity, and effects on radiation responses. RESULTS: We showed that the
      nanoparticles penetrate D. radiodurans cells, despite the 150 nm cell wall
      thickness with a minimal inhibition concentration on the order of 4.8 mg L-1. We
      also found that the nanoparticles amplify gamma ray radiation effects by >40%.
      CONCLUSIONS: Finally, this study demonstrates the capacity of metallic
      nanoparticles to amplify radiation in radioresistant organisms, thus opening the
      perspective to use nanoparticles not only to improve tumour targeting but also to
      overcome radioresistance.

PMID- 28757900
TI  - The Effectiveness of Mindfulness-Based Interventions on Maternal Perinatal Mental
      Health Outcomes: a Systematic Review.
AB  - Presenting with common mental health difficulties, particularly depression and
      anxiety, there is also preliminary evidence that mindfulness-based interventions
      (MBIs) including mindfulness-based cognitive therapy (MBCT), mindfulness-based
      stress reduction (MBSR) and integrated mindfulness yoga practices may also be
      effective in reducing common mental health difficulties during pregnancy. We
      systematically reviewed and synthesized the current literature on the
      effectiveness of MBIs in reducing severity of perinatal anxiety and depression.
      Databases including PubMed, Cochrane Library, IndMED and PsychoInfo were searched
      for relevant studies. Manual searches were conducted in relevant articles and
      Google Scholar. Seventeen cohorts representing 18 studies were included. Pre-post
      effect sizes were reported for both treatment and control groups. Seven
      randomized controlled trials (RCTs), two non-randomized controlled trials and
      nine treatment evaluations were included. Maternal participation in an MBI was
      associated with reductions in perinatal anxiety of moderate to large magnitude.
      Results for the effect of MBIs on depression were less consistent, with pre-post
      treatment reductions of moderate magnitude, but no significant differences in
      depression scores when MBI was compared with a control group. There was some
      evidence that MBIs were associated with increased mindfulness. Risk of bias in
      studies was variable. Our review offers preliminary evidence for the
      effectiveness of MBIs in reducing perinatal anxiety, with more equivocal findings
      with regard to perinatal depressive symptoms. Further methodologically rigorous
      evaluation using RCTs and longer follow-up periods are recommended.

PMID- 28757901
TI  - Teacher Competence in Mindfulness-Based Cognitive Therapy for Depression and Its
      Relation to Treatment Outcome.
AB  - As mindfulness-based cognitive therapy (MBCT) becomes an increasingly mainstream
      approach for recurrent depression, there is a growing need for practitioners who
      are able to teach MBCT. The requirements for being competent as a mindfulness
      based teacher include personal meditation practice and at least a year of
      additional professional training. This study is the first to investigate the
      relationship between MBCT teacher competence and several key dimensions of MBCT
      treatment outcomes. Patients with recurrent depression in remission (N = 241)
      participated in a multi-centre trial of MBCT, provided by 15 teachers. Teacher
      competence was assessed using the Mindfulness-Based Interventions: Teaching
      Assessment Criteria (MBI:TAC) based on two to four randomly selected video
      recorded sessions of each of the 15 teachers, evaluated by 16 trained assessors.
      Results showed that teacher competence was not significantly associated with
      adherence (number of MBCT sessions attended), possible mechanisms of change
      (rumination, cognitive reactivity, mindfulness, and self-compassion), or key
      outcomes (depressive symptoms at post treatment and depressive relapse/recurrence
      during the 15-month follow-up). Thus, findings from the current study indicate no
      robust effects of teacher competence, as measured by the MBI:TAC, on possible
      mediators and outcome variables in MBCT for recurrent depression. Possible
      explanations are the standardized delivery of MBCT, the strong emphasis on self
      reliance within the MBCT learning process, the importance of participant-related
      factors, the difficulties in assessing teacher competence, the absence of main
      treatment effects in terms of reducing depressive symptoms, and the relatively
      small selection of videotapes. Further work is required to systematically
      investigate these explanations.

PMID- 28757902
TI  - Resting Brain Activity Related to Dispositional Mindfulness: a PET Study.
AB  - Mindfulness denotes a state of consciousness characterized by receptive attention
      to and awareness of present events and experiences. As a personality trait, it
      constitutes the ability to become aware of mental activities such as sensations,
      images, feelings, and thoughts, and to disengage from judgment, conditioned
      emotions, and their cognitive processing or automatic inhibition. Default brain
      activity reflects the stream of consciousness and sense of self at rest. Analysis
      of brain activity at rest in persons with mindfulness propensity may help to
      elucidate the neurophysiological basis of this important mental trait. The sample
      consisted of 32 persons-23 with mental disorders and 9 healthy controls.
      Dispositional mindfulness (DM) was operationalized by Mindful Attention Awareness
      Scale (MAAS). Brain activity at rest with eyes closed was assessed by
      fluorodeoxyglucose positron emission tomography (F-18-FDG PET). After adjustment
      for depression, anxiety, age and years of education, resting glucose metabolism
      in superior parietal lobule and left precuneus/Brodmann area (BA) 7 was
      positively associated with DM. Activity of the left inferior frontal orbital
      gyrus (BA 47) and bilateral anterior thalamus were inversely associated with DM.
      DM appears to be associated with increased metabolic activity in some core area
      of the default mode network (DMN) and areas connected to the DMN, such as BA 7,
      hosting sense of self functions. Hypometabolism on the other hand was found in
      some nodes connected to the DMN, such as left inferior frontal orbital gyrus and
      bilateral thalamus, commonly related to functions of memory retrieval, decision
      making, or outward attention.

PMID- 28757903
TI  - For Whom Does Mindfulness-Based Stress Reduction Work? Moderating Effects of
      Personality.
AB  - The aim of the present study was to examine potentially moderating effects of
      personality characteristics regarding changes in anxious and depressed mood
      associated with Mindfulness-Based Stress Reduction (MBSR), controlling for socio
      demographic factors. Meditation-naive participants from the general population
      self-presenting with psychological stress complaints (n = 167 participants, 70%
      women, mean age 45.8 +/- 9.3 years) were assessed in a longitudinal investigation
      of change in mood before and after the intervention and at a 3-month follow-up.
      Participants initially scoring high on neuroticism showed stronger decreases in
      both anxious and depressed mood (both p < 0.001). However, when controlled for
      baseline mood, only the time by neuroticism interaction effect on anxiety
      remained significant (p = 0.001), reflecting a smaller decrease in anxiety
      between pre- and post-intervention but a larger decrease in anxiety between post
      intervention and follow-up in those with higher baseline neuroticism scores. Most
      personality factors did not show moderating effects, when controlled for baseline
      mood. Only neuroticism showed to be associated with delayed benefit. Results are
      discussed in the context of findings from similar research using more traditional
      cognitive-behavioral interventions.

PMID- 28757904
TI  - The Relationships Among Socio-Demographics, Perceived Health, and Happiness.
AB  - This article explores explore the relationships among socio-demographics,
      perceived health, and happiness in a patient population of 221 adults recruited
      from 39 primary care practices in Alabama. We also explored whether the
      relationship between socio-demographics and happiness is mediated by perceived
      health. The dependent variable, happiness, was dichotomized as happy versus
      unhappy. Independent variables or correlates of happiness included race (Black or
      White), age (< 65 vs. 65 and older), gender (male vs. female), perceived income
      (sufficient vs. insufficient to meet basic needs), health literacy (adequate vs.
      inadequate), and self-rated health (excellent/very good/good vs. poor/fair). Data
      were analyzed using generalized linear latent and mixed models to examine the
      relationship between happiness and its correlates. Our findings suggest that
      adequate health literacy and better perceived health are associated with an
      increase in the likelihood of happiness. In addition, the relationship between
      perceived sufficient income and happiness is mediated by perceived health;
      whereas, individuals with sufficient income are more likely to have better
      perceived health, and as a result more likely to be happy. Other individual
      factors, such as gender, age, and race were not significantly associated with
      being happy or having higher perceived health in any of the models. Results
      suggest that policies aimed at increasing health literacy, promoting health, and
      reducing income disparities may be associated with greater happiness.

PMID- 28757905
TI  - [The "weak and sensitive elements" of the pediatric and adolescents' clinical
      trials].
AB  - The ethical review of clinical research on children and adolescents should be
      centered in aspects related to their condition of vulnerability, which is
      nurtured by biological, emotional, equity and justice elements.However, the
      suggested vision in this case, without overlooking previously mentioned
      characteristics, is the one that seeks to delve deeper in one of the actors of
      the research process: the clinical research protocol.The objective is to
      determine the presence or not of "fragile zones or weak spots" in its interior,
      that when individualized and considered, will contribute to improve the quality
      of the ethical review on children and adolescent research.

PMID- 28757907
TI  - Mind your crossings: Mining GIS imagery for crosswalk localization.
AB  - For blind travelers, finding crosswalks and remaining within their borders while
      traversing them is a crucial part of any trip involving street crossings. While
      standard Orientation & Mobility (O&M) techniques allow blind travelers to safely
      negotiate street crossings, additional information about crosswalks and other
      important features at intersections would be helpful in many situations,
      resulting in greater safety and/or comfort during independent travel. For
      instance, in planning a trip a blind pedestrian may wish to be informed of the
      presence of all marked crossings near a desired route. We have conducted a survey
      of several O&M experts from the United States and Italy to determine the role
      that crosswalks play in travel by blind pedestrians. The results show stark
      differences between survey respondents from the U.S. compared with Italy: the
      former group emphasized the importance of following standard O&M techniques at
      all legal crossings (marked or unmarked), while the latter group strongly
      recommended crossing at marked crossings whenever possible. These contrasting
      opinions reflect differences in the traffic regulations of the two countries and
      highlight the diversity of needs that travelers in different regions may have. To
      address the challenges faced by blind pedestrians in negotiating street
      crossings, we devised a computer vision-based technique that mines existing
      spatial image databases for discovery of zebra crosswalks in urban settings. Our
      algorithm first searches for zebra crosswalks in satellite images; all candidates
      thus found are validated against spatially registered Google Street View images.
      This cascaded approach enables fast and reliable discovery and localization of
      zebra crosswalks in large image datasets. While fully automatic, our algorithm
      can be improved by a final crowdsourcing validation. To this end, we developed a
      Pedestrian Crossing Human Validation (PCHV) web service, which supports
      crowdsourcing to rule out false positives and identify false negatives.

PMID- 28757908
TI  - Lysosomes as Oxidative Targets for Cancer Therapy.
AB  - Lysosomes are membrane-bound vesicles that contain hydrolases for the degradation
      and recycling of essential nutrients to maintain homeostasis within cells. Cancer
      cells have increased lysosomal function to proliferate, metabolize, and adapt to
      stressful environments. This has made cancer cells susceptible to lysosomal
      membrane permeabilization (LMP). There are many factors that mediate LMP such as
      Bcl-2 family member, p53; sphingosine; and oxidative stress which are often
      altered in cancer. Upon lysosomal disruption, reactive oxygen species (ROS)
      levels increase leading to lipid peroxidation, mitochondrial dysfunction,
      autophagy, and reactive iron. Cathepsins are also released causing degradation of
      macromolecules and cellular structures. This ultimately kills the cancer cell
      through different types of cell death (apoptosis, autosis, or ferroptosis). In
      this review, we will explore the contributions lysosomes play in inducing cell
      death, how this is regulated by ROS in cancer, and how lysosomotropic agents
      might be utilized to treat cancers.

PMID- 28757909
TI  - Metabolic Reprogramming, Autophagy, and Reactive Oxygen Species Are Necessary for
      Primordial Germ Cell Reprogramming into Pluripotency.
AB  - Cellular reprogramming is accompanied by a metabolic shift from oxidative
      phosphorylation (OXPHOS) toward glycolysis. Previous results from our laboratory
      showed that hypoxia alone is able to reprogram primordial germ cells (PGCs) into
      pluripotency and that this action is mediated by hypoxia-inducible factor 1
      (HIF1). As HIF1 exerts a myriad of actions by upregulating several hundred genes,
      to ascertain whether the metabolic switch toward glycolysis is solely responsible
      for reprogramming, PGCs were cultured in the presence of a pyruvate kinase M2
      isoform (PKM2) activator, or glycolysis was promoted by manipulating PPARgamma.
      Conversely, OXPHOS was stimulated by inhibiting PDK1 activity in normoxic or in
      hypoxic conditions. Inhibition or promotion of autophagy and reactive oxygen
      species (ROS) production was performed to ascertain their role in cell
      reprogramming. Our results show that a metabolic shift toward glycolysis,
      autophagy, and mitochondrial inactivation and an early rise in ROS levels are
      necessary for PGC reprogramming. All of these processes are governed by HIF1/HIF2
      balance and strict intermediate Oct4 levels. Histone acetylation plays a role in
      reprogramming and is observed under all reprogramming conditions. The pluripotent
      cells thus generated were unable to self-renew, probably due to insufficient
      Blimp1 downregulation and a lack of Klf4 and cMyc expression.

PMID- 28757906
TI  - Lumbosacral Dorsal Rhizotomy for Spastic Cerebral Palsy: A Health Technology
      Assessment.
AB  - BACKGROUND: Cerebral palsy, a spectrum of neuromuscular conditions caused by
      abnormal brain development or early damage to the brain, is the most common cause
      of childhood physical disability. Lumbosacral dorsal rhizotomy is a neurosurgical
      procedure that permanently decreases spasticity and is always followed by
      physical therapy. The objectives of this health technology assessment were to
      evaluate the clinical effectiveness, safety, cost effectiveness, and family
      perspectives of dorsal rhizotomy. METHODS: We performed a systematic literature
      search until December 2015 with auto-alerts until December 2016. Search
      strategies were developed by medical librarians, and a single reviewer reviewed
      the abstracts. The health technology assessment included a clinical review based
      on functional outcomes, safety, and treatment satisfaction; an economic study
      reviewing cost-effective literature; a budget impact analysis; and interviews
      with families evaluating the intervention. RESULTS: Eighty-four studies (1 meta
      analysis, 5 randomized controlled studies [RCTs], 75 observational pre-post
      studies, and 3 case reports) were reviewed. A meta-analysis of RCTs involving
      dorsal rhizotomy and physical therapy versus physical therapy confirmed reduced
      lower-limb spasticity and increased gross motor function (4.5%, P = .002).
      Observational studies reported statistically significant improvements in gross
      motor function over 2 years or less (12 studies, GRADE moderate) and over more
      than 2 years (10 studies, GRADE moderate) as well as improvements in functional
      independence in the short term (10 studies, GRADE moderate) and long term (4
      studies, GRADE low). Major operative complications, were infrequently reported (4
      studies). Bony abnormalities and instabilities monitored radiologically in the
      spine (15 studies) and hip (8 studies) involved minimal or clinically
      insignificant changes after surgery. No studies evaluated the cost effectiveness
      of dorsal rhizotomy. The budget impact of funding dorsal rhizotomy for treatment
      of Ontario children with cerebral palsy was $1.3 million per year. Families
      reported perceived improvements in their children and expressed satisfaction with
      treatment. Ontario families reported inadequate medical information on benefits
      or risk to make an informed decision, enormous financial burdens, and lack
      rehabilitation support after surgery. CONCLUSIONS: Lumbrosacral dorsal rhizotomy
      and physical therapy effectively reduces lower-limb spasticity in children with
      spastic cerebral palsy and significantly improves their gross motor function and
      functional independence. Major peri-operative complications were infrequently
      reported. Families reported perceived improvements with dorsal rhizotomy, and
      surgery and post-operative rehabilitation were intensive and demanding.

PMID- 28757910
TI  - Curcumin Protects Skin against UVB-Induced Cytotoxicity via the Keap1-Nrf2
      Pathway: The Use of a Microemulsion Delivery System.
AB  - Curcumin was found to be beneficial in treating several skin pathologies and
      diseases, providing antioxidant protection due to its reducing properties and its
      electrophilic properties (the ability to activate the Nrf2 pathway and induce
      phase II cytoprotective enzymes). Nevertheless, clinical applications of curcumin
      are being hampered by its insufficient solubility, chemical instability, and poor
      absorption, leading to low efficacy in preventing skin pathologies. These
      limitations can be overcome by using a nanotechnology-based delivery system.
      Here, we elucidated the possibility of using curcumin encapsulated in a
      microemulsion preserving its unique chemical structure. We also examined whether
      curcumin microemulsion would reduce UVB-induced toxicity in skin. A significant
      curcumin concentration was found in the human skin dermis following topical
      application of a curcumin microemulsion. Moreover, curcumin microemulsion
      enhanced the reduction of UV-induced cytotoxicity in epidermal cells, paving the
      way for other incorporated electrophiles in encapsulated form protecting skin
      against stress-related diseases.

PMID- 28757911
TI  - Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of
      Oxidative Stress, Inflammation, and NRF2 Transcription Factor.
AB  - Experimental cholestatic liver fibrosis was performed by bile duct ligation (BDL)
      in mice, and significant liver injury was observed in 15 days. Administration of
      baicalin in mice significantly ameliorates liver fibrosis. Experimental
      cholestatic liver fibrosis was associated with induced gene expression of
      fibrotic markers such as collagen I, fibronectin, alpha smooth muscle actin
      (SMA), and connective tissue growth factor (CTGF); increased inflammatory
      cytokines (TNFalpha, MIP1alpha, IL1beta, and MIP2); increased oxidative stress
      and reactive oxygen species- (ROS-) inducing enzymes (NOX2 and iNOS);
      dysfunctional mitochondrial electron chain complexes; and apoptotic/necrotic cell
      death markers (DNA fragmentation, caspase 3 activity, and PARP activity).
      Baicalin administration on alternate day reduced fibrosis along with profibrotic
      gene expression, proinflammatory cytokines, oxidative stress, and cell death
      whereas improving the function of mitochondrial electron transport chain. We
      observed baicalin enhanced NRF2 activation by nuclear translocation and induced
      its target genes HO-1 and GCLM, thus enhancing antioxidant defense. Interplay of
      oxidative stress/inflammation and NRF2 were key players for baicalin-mediated
      protection. Stellate cell activation is crucial for initiation of fibrosis.
      Baicalin alleviated stellate cell activation and modulated TIMP1, SMA, collagen
      1, and fibronectin in vitro. This study indicates that baicalin might be
      beneficial for reducing inflammation and fibrosis in liver injury models.

PMID- 28757914
TI  - Evaluating Anti-Infective Drugs in the Resistant Pathogen Setting: Can we Use
      External Controls?
AB  - Decreased efficacy of antibiotics due to resistant pathogens has created a need
      for the development of more effective medical interventions. Despite the
      increasing prevalence of pathogens resistant to one or more drugs, identifying
      and enrolling participants into clinical trials that evaluate new interventions
      for the treatment of some diseases can be challenging given the low prevalence of
      disease in which there are no effective treatments. Thus researchers might be
      tempted to consider externally-controlled trials that may allow for a reduction
      of the necessary number of prospectively-identified trial participants, thus
      easing recruitment burden and resulting in more timely trial completion relative
      to randomized controlled trials. We discuss advantages and disadvantages in
      externally controlled trials and review requirements for a valid externally
      controlled trial. As ECTs are subject to the bias of observational studies, the
      criteria for a valid ECT should be carefully evaluated before these designs are
      implemented. Given considerable variation in study results in the resistant
      pathogen setting, the lack of information on important patient characteristics
      that may confound estimates of treatment effects, as well as the improvements in
      medical practice and evolving antibiotic resistance, the use of ECTs in the
      resistant pathogen setting, is not recommended. ECTs should be should be limited
      to specific situations where superiority of the effect of the new intervention is
      dramatic, the usual course of the disease highly predictable, the endpoints are
      objective (e.g., all-cause mortality) and the impact of baseline and treatment
      variables on outcomes is well characterized. Given that the resistant pathogen
      setting does not satisfy these criteria, we conclude that that randomized
      clinical trials are needed to evaluate new treatments for resistant pathogens.
      Innovative approaches to trial design that may ease recruitment burden while
      evaluating the benefits and harms of new treatments are being developed and
      utilized.

PMID- 28757912
TI  - Lung-Protective Ventilation Strategies for Relief from Ventilator-Associated Lung
      Injury in Patients Undergoing Craniotomy: A Bicenter Randomized, Parallel, and
      Controlled Trial.
AB  - Current evidence indicates that conventional mechanical ventilation often leads
      to lung inflammatory response and oxidative stress, while lung-protective
      ventilation (LPV) minimizes the risk of ventilator-associated lung injury (VALI).
      This study evaluated the effects of LPV on relief of pulmonary injury,
      inflammatory response, and oxidative stress among patients undergoing craniotomy.
      Sixty patients undergoing craniotomy received either conventional mechanical (12
      mL/kg tidal volume [VT] and 0 cm H2O positive end-expiratory pressure [PEEP]; CV
      group) or protective lung (6 mL/kg VT and 10 cm H2O PEEP; PV group) ventilation.
      Hemodynamic variables, lung function indexes, and inflammatory and oxidative
      stress markers were assessed. The PV group exhibited greater dynamic lung
      compliance and lower respiratory index than the CV group during surgery (P <
      0.05). The PV group exhibited higher plasma interleukin- (IL-) 10 levels and
      lower plasma malondialdehyde and nitric oxide and bronchoalveolar lavage fluid,
      IL-6, IL-8, tumor necrosis factor-alpha, IL-10, malondialdehyde, nitric oxide,
      and superoxide dismutase levels (P < 0.05) than the CV group. There were no
      significant differences in hemodynamic variables, blood loss, liquid input, urine
      output, or duration of mechanical ventilation between the two groups (P > 0.05).
      Patients receiving LPV during craniotomy exhibited low perioperative inflammatory
      response, oxidative stress, and VALI.

PMID- 28757915
TI  - Diagnosis of occipital neuralgia due to upper cervical chordoma.

PMID- 28757913
TI  - The Involvement of Mg2+ in Regulation of Cellular and Mitochondrial Functions.
AB  - Mg2+ is an essential mineral with pleotropic impacts on cellular physiology and
      functions. It acts as a cofactor of several important enzymes, as a regulator of
      ion channels such as voltage-dependent Ca2+ channels and K+ channels and on Ca2+
      binding proteins. In general, Mg2+ is considered as the main intracellular
      antagonist of Ca2+, which is an essential secondary messenger initiating or
      regulating a great number of cellular functions. This review examines the effects
      of Mg2+ on mitochondrial functions with a particular focus on energy metabolism,
      mitochondrial Ca2+ handling, and apoptosis.

PMID- 28757916
TI  - Bone scintigraphy in patients with pain.
AB  - Nuclear medicine imaging is widely used in pain medicine. Low back pain is
      commonly encountered by physicians, with its prevalence from 49% to 70%. Computed
      tomography (CT) or magnetic resonance imaging (MRI) are usually used to evaluate
      the cause of low back pain, however, these findings from these scans could also
      be observed in asymptomatic patients. Bone scintigraphy has an additional value
      in patients with low back pain. Complex regional pain syndrome (CRPS) is defined
      as a painful disorder of the extremities, which is characterized by sensory,
      autonomic, vasomotor, and trophic disturbances. To assist the diagnosis of CRPS,
      three-phase bone scintigraphy is thought to be superior compared to other
      modalities, and could be used to rule out CRPS due to its high specificity.
      Studies regarding the effect of bone scintigraphy in patients with extremity pain
      have not been widely conducted. Ultrasound, CT and MRI are widely used imaging
      modalities for evaluating extremity pain. However, SPECT/CT has an additional
      role in assessing pain in the extremities.

PMID- 28757917
TI  - Intravenous caffeine citrate vs. magnesium sulfate for reducing pain in patients
      with acute migraine headache; a prospective quasi-experimental study.
AB  - BACKGROUND: Current evidence suggests that intravenous magnesium sulfate might be
      effective for reducing migraine pain. In a recent pilot study, we showed that
      intravenous caffeine citrate could reduce the severity of migraine headache. The
      objective of this study is to investigate the efficacy of intravenous caffeine
      citrate vs. magnesium sulfate for management of acute migraine headache. METHODS:
      We conducted a prospective quasi-experimental study from January until May 2016
      in two educational medical centers of Shahid Beheshti University of Medical
      Sciences (Shoahadaye Tajrish Hospital and Imam Hossein Hospital), Tehran, Iran.
      The study included patients who were referred to the emergency department and met
      the migraine diagnosis criteria of the International Headache Society. Patients
      were allocated into 2 groups receiving either 60 mg intravenous caffeine or 2 g
      intravenous magnesium sulfate. The pain scores, based on the visual analog scale,
      were recorded on admission, as well as one and two hours after receiving the
      drug. A Chi-Square test and student t-test were used for analysis of baseline
      characteristics. A Mann-Whitney U test and Wilcoxon singed rank test were used to
      analyze differences in the visual analogue scale (VAS) score between and within
      the groups respectively. RESULTS: In total, 70 patients (35 patients in each
      group) with the mean age of 33.1 +/- 11.3 years were included (64.3% female). For
      the Caffeine citrate group, the median pain score decreased from 9.0 (2.0) to 5.0
      (4.0) after one hour and to 3.0 (4.0) after two hours. For the magnesium sulfate
      group, the pain score decreased from 8.0 (2.0) to 2.0 (2.0) after one hour and to
      0.0 (1.0) after two hours. Both intravenous caffeine citrate and intravenous
      magnesium sulfate reduced pain scores significantly but the magnesium sulfate
      group showed more improvement than the Caffeine citrate group after one hour (P <
      0.001) and after two hours (P < 0.001). CONCLUSIONS: It is likely that both
      intravenous caffeine and intravenous magnesium sulfate can reduce the severity of
      migraine headache. Moreover, intravenous magnesium sulfate at a dose of 2 g might
      be superior to intravenous caffeine citrate 60 mg for the short term management
      of migraine headache in emergency departments.

PMID- 28757918
TI  - Low doses of amitriptyline, pregabalin, and gabapentin are preferred for
      management of neuropathic pain in India: is there a need for revisiting dosing
      recommendations?
AB  - BACKGROUND: Current therapy for the treatment of neuropathic pain is often
      unsatisfactory. Considerable variation in treatment pattern still exists in spite
      of availability of sufficient literature from various guidelines. Recent Indian
      market data suggested that the utilization (sale) of drugs such as amitriptyline,
      pregabalin, and gabapentin was more for low-dose unit packs than that of the high
      dose unit packs, raising the belief that these drugs are prescribed at a lower
      dose than is actually recommended in the guidelines. To test this hypothesis, a
      survey was conducted across speciality throughout the country to observe the
      prescription pattern of these drugs amongst the health care providers in India.
      METHODS: Three hundred fifty survey forms were distributed of which 281 forms
      were included for analysis. RESULTS: It was observed that the commonly used
      initiation and maintenance dose for amitriptyline, pregabalin, and gabapentin was
      5-10 mg/day, 50-75 mg/day, and 100-300 mg/day, respectively. The reason to select
      the lower dosages was to have a balancing effect to achieve good efficacy with
      minimum side effects. Care-givers reported no side effects/not many side effects
      as a reason in 22.2%, 16.88%, and 23.86% patients with amitriptyline, pregabalin,
      and gabapentin, respectively. Sedation and giddiness were commonly reported with
      all three drugs. CONCLUSIONS: Commonly prescribed drugs for management of
      neuropathic pain, such as amitriptyline, pregabalin, and gabapentin are preferred
      at lower doses in Indian clinical settings. Acceptable efficacy and low tolerance
      to the standard dosage is believed to be the reason behind the prescribed dose.

PMID- 28757919
TI  - Effects of musculoskeletal system problems on quality of life and depression in
      students preparing for university entrance exam.
AB  - BACKGROUND: This study was planned to investigate the relationship between
      musculoskeletal problems, depression, and quality of life in students preparing
      for university entrance exams. METHODS: A total of 180 students were included in
      the study, 104 were female (57.77%), and 76 were male (42.22%). Students were
      reached through the cram schools ("dershane") in Denizli. Musculoskeletal system
      problems, depression status, and quality of life were determined with the
      Musculoskeletal-Postural Discomfort Scale (MDS), Boratav Depression Screen Scale
      (Bordepta), and Short Form-36 (SF-36), respectively. Demographic data, daily
      study, and sleep duration were also recorded. RESULTS: Students have moderate
      musculoskeletal discomfort. Musculoskeletal disorders and depressive symptoms are
      more observed in female students than male students (P = 0.000). The SF-36
      results were significantly negatively correlated with the MDS and Bordepta
      scores. A significant positive correlation was found between musculoskeletal
      disorders and depression status (r = 0.351, P = 0.000). Sleep duration was
      negatively correlated with the MDS and Bordepta (r = -0.209, P = 0.005; r = 
      0.148, P = 0.047, respectively) and positively correlated with the SF-36 role
      limitation/emotional and social functioning subscales (r = 0.225, P = 0.002 and r
      = 0.191, P = 0.010 respectively). CONCLUSIONS: Musculoskeletal problems and
      depression status negatively affects general health status especially in female
      students who are preparing for university entrance examinations. Students should
      be informed about musculoskeletal problems by healthcare professionals and the
      study room, tables, and chairs should be arranged ergonomically. Further studies
      might be determined that why musculoskeletal disorders and depression status are
      more widely among female students.

PMID- 28757920
TI  - Hindi version of short form of douleur neuropathique 4 (S-DN4) questionnaire for
      assessment of neuropathic pain component: a cross-cultural validation study.
AB  - BACKGROUND: Pain with neuropathic characteristics is generally more severe and
      associated with a lower quality of life compared to nociceptive pain (NcP). Short
      form of the Douleur Neuropathique en 4 Questions (S-DN4) is one of the most used
      and reliable screening questionnaires and is reported to have good diagnostic
      properties. This study was aimed to cross-culturally validate the Hindi version
      of the S-DN4 in patients with various chronic pain conditions. METHODS: The S-DN4
      is already translated into the Hindi language by Mapi Research Trust. This study
      assessed the psychometric properties of the Hindi version of the S-DN4 including
      internal consistency and test-retest reliability after 3 days' post-baseline
      assessment. Diagnostic performance was also assessed. RESULTS: One hundred sixty
      patients with chronic pain, 80 each in the neuropathic pain (NeP) present and NeP
      absent groups, were recruited. Patients with NeP present reported significantly
      higher S-DN4 scores in comparison to patients in the NeP absent group (mean (SD),
      4.7 (1.7) vs. 1.8 (1.6), P < 0.01). The S-DN4 was found to have an AUC of 0.88
      with adequate internal consistency (Cronbach's alpha = 0.80) and a test-retest
      reliability (ICC = 0.92) with an optimal cut-off value of 3 (Youden's index =
      0.66, sensitivity and specificity of 88.7% and 77.5%). The diagnostic concordance
      rate between clinician diagnosis and the S-DN4 questionnaire was 83.1% (kappa =
      0.66). CONCLUSIONS: Overall, the Hindi version of the S-DN4 has good internal
      consistency and test-retest reliability along with good diagnostic accuracy.

PMID- 28757921
TI  - The impact of magnesium sulfate as adjuvant to intrathecal bupivacaine on intra
      operative surgeon satisfaction and postoperative analgesia during laparoscopic
      gynecological surgery: randomized clinical study.
AB  - BACKGROUND: Surgeon satisfaction and patient analgesia during the procedure of
      laparoscopic surgery are important issues. The aim of this work was to study if
      an intrathecal (IT) Bupivacaine combined with Magnesium sulfate may or may not
      provide good surgeon satisfaction in addition to improvement of intraoperative
      and postoperative analgesia. METHODS: Sixty female patients were enrolled in this
      prospective, randomized, double-blind controlled clinical trial study. All
      patients were operated for gynecological laparoscopic surgery under spinal
      anesthesia. Patients were divided into two groups (Bupivacaine and Magnesium).
      Group Bupivacaine (30 patients) received intrathecal Bupivacaine 0.5% only (15
      mg), while 30 patients in group Magnesium received intrathecal Bupivacaine (15
      mg) in addition to intrathecal Magnesium sulfate (50 mg). The sensory block
      level, the intensity of motor block, the surgeon satisfaction, the intraoperative
      visual analog scale (VAS) for pain assessment, the postoperative VAS, and side
      effects were recorded during the intraoperative period and within the first 24
      hours after surgery in the post-anesthesia care unit. RESULTS: Surgeon
      satisfaction, intraoperative shoulder pain, postoperative pain after 2 h, and
      perioperative analgesic consumption (ketorolac) were significant better in group
      Magnesium than in group Bupivacaine. (P < 0.05). The onset of motor and sensory
      blocks was significant longer in group Magnesium than the other one. The
      incidence of PONV, pruritus and urinary retention was insignificant statistically
      between both groups. CONCLUSIONS: Magnesium sulfate if used intrathecally as an
      adjuvant to Bupivacaine would provide a better surgeon satisfaction and would
      improve the analgesic effect of spinal anesthesia used for gynecological
      laparoscopic surgery.

PMID- 28757922
TI  - Earlier treatment improves the chances of complete relief from postherpetic
      neuralgia.
AB  - BACKGROUND: As herpes zoster progresses via postherpetic neuralgia (PHN) to well
      established PHN, it presents its recalcitrant nature to the treatment. At this
      point, the well-established PHN is fixed as a non-treatable, but manageable
      chronic painful neuropathic disorder. This study evaluated the incidence of
      complete relief from PHN according to PHN duration at their first visit, and the
      other factors influencing it. METHODS: A retrospective chart review was performed
      on patients with PHN at a university-based pain clinic over 7 years. The
      responders were defined as patients who had complete relief from pain after 1
      year of active treatment. Age, sex, PHN duration at their first visit, dermatomal
      distribution, and underlying disorders were compared in the responder and non
      responder groups. Responders were also compared according to these factors.
      RESULTS: Among 117 PHN patients (M/F = 48/69), 35 patients (29.9%) had complete
      relief from PHN. Mean ages were 64.3 +/- 10.6 and 66.9 +/- 10.7 years, numbers of
      male to female patients were 11/24 and 37/45, and mean durations of PHN at their
      first visit were 8.5 +/- 6.3 and 15.3 +/- 10.7 months in the responder and non-
      responder groups, respectively. In addition, PHN patients who visited the clinic
      before 9 months showed a better result. Dermatomal distribution and underlying
      disorders did not show significant differences. CONCLUSIONS: Almost 30% of PHN
      patients received complete relief. Those who sought treatment in a pain clinic
      before 9 months received a better result.

PMID- 28757923
TI  - Comparison of clinical efficacy in epidural steroid injections through
      transforaminal or parasagittal approaches.
AB  - BACKGROUND: The transforaminal (TF) epidural steroid injection (ESI) is suggested
      as more effective than the interlaminar (IL) route due to higher delivery of
      medication at the anterior epidural space. However, serious complications such as
      spinal cord injury and permanent neural injury have been reported. The purpose of
      this study is to evaluate and compare the clinical effectiveness, technical ease,
      and safety of the TF and parasagittal IL (PIL) ESI. METHODS: A total of 72
      patients were randomized to either the PIL group (n = 41) or the TF group (n =
      31) under fluoroscopic guidance. Patients were evaluated for effective pain
      relief by the numerical rating scale (NRS) and Oswestry Disability Index (ODI)
      (%) before and 2 weeks after the ESI. The presence of concordant paresthesia,
      anterior epidural spread, total procedure time, and exposed radiation dose were
      also evaluated. RESULTS: Both the PIL and TF approach produced similar clinically
      significant improvements in pain and level of disability. Among the 72 patients,
      27 PIL (66%) and 20 TF (64%) patients showed concordant paresthesia while 14
      (34%) and 11 (36%) patients in the same respective order showed disconcordant or
      no paresthesia. Radiation dose and total procedure time required were compared;
      the PIL group showed a significantly lower radiation dose (30.2 +/- 12 vs. 80.8
      +/- 26.8 [Cgy/cm2]) and shorter procedure time (96.2 +/- 31 vs. 141.6 +/- 30
      seconds). CONCLUSIONS: ESI under fluoroscopic guidance with PIL or TF approach
      were effective in reducing the NRS and ODI. PIL ESI was a technically easier and
      simple method compared to TF ESI.

PMID- 28757924
TI  - Spinal cord stimulation for a patient with neuropathic pain related to congenital
      syringomyelia.

PMID- 28757925
TI  - Passive Leg Raising: Simple and Reliable Technique to Prevent Fluid Overload in
      Critically ill Patients.
AB  - BACKGROUND: Dynamic measures, the response to stroke volume (SV) to fluid
      loading, have been used successfully to guide fluid management decisions in
      critically ill patients. However, application of dynamic measures is often
      inaccurate to predict fluid responsiveness in patients with arrhythmias,
      ventricular dysfunction or spontaneously breathing critically ill patients.
      Passive leg raising (PLR) is a simple bedside maneuver that may provide an
      accurate alternative to guide fluid resuscitation in hypovolemic critically ill
      patients. METHODS: Pertinent medical literature for fluid responsiveness in the
      critically ill patient published in English was searched over the past three
      decades, and then the search was extended as linked citations indicated. RESULTS:
      Thirty-three studies including observational studies, randomized control trials,
      systemic review, and meta-analysis studies evaluating fluid responsiveness in the
      critically ill patient met selection criteria. CONCLUSIONS: PLR coupled with real
      time SV monitors is considered a simple, noninvasive, and accurate method to
      determine fluid responsiveness in critically ill patients with high sensitivity
      and specificity for a 10% increase in SV. The adverse effect of albumin on the
      mortality of head trauma patients and chloride-rich crystalloids on mortality and
      kidney function needs to be considered when choosing the type of fluid for
      resuscitation.

PMID- 28757926
TI  - Awareness of the Necessity of Regular Eye Examinations among Diabetics: The Yazd
      Eye Study.
AB  - BACKGROUND: Diabetic retinopathy and its consequence, diabetic macular edema, are
      leading causes of vision loss in diabetics and can develop even in the first
      years after onset of diabetes. Being asymptomatic in primary phase and having
      compensatory effect of bilateral vision delay the necessity of eye care
      utilization. We conducted this study to determine diabetic individuals' level of
      awareness about the importance of regular eye examinations. METHODS: As part of
      the cross-sectional, population-based, Yazd Eye Study on people aged 40-80 years,
      diabetic participants were identified for enrollment in this research.
      Participants underwent thorough ophthalmic examinations as well as detailed
      interview. Well-trained interviewers asked participants about their awareness of
      screening eye examinations and their necessity. Fasting blood sugar, glycated
      hemoglobin, and complete lipid profile were assessed. All descriptive and
      analytic tests were done in survey mode. Logistic regression was applied to
      assess related risk factors. RESULTS: Among 497 diabetic persons out of 2098
      participants, 364 respondents (73.4%; 95% confidence interval: 68.6-78.2) were
      not aware of the necessity of regular eye examinations. Among 133 aware
      respondents, 21 (16%) respondents had no eye examination over the past year.
      Educational level significantly correlated with awareness (P = 0.004), and
      physicians were the most frequent source of awareness (79.7%). CONCLUSIONS: This
      study showed that a significant proportion of Yazd diabetic population (about
      73%) needs to be informed about the necessity of regular eye examinations. The
      remaining respondents, who had this information, mainly had undergone regular
      ophthalmologist visits, which imply that educational interventions could improve
      the situation.

PMID- 28757927
TI  - A Randomized Clinical Trial on Treatment of Chronic Constipation by Traditional
      Persian Medicine Recommendations Compared to Allopathic Medicine: A Pilot Study.
AB  - BACKGROUND: The aim of this study was to compare the efficacy and side effects of
      lactulose plus traditional Persian medicine with only lactulose on the functional
      chronic constipation. METHODS: Participants included 20 patients (10 in each
      group) aged 18-80 years, with major inclusion criteria of ROME III. They were
      assigned into two parallel therapeutic groups, including the intervention group
      (lactulose plus traditional Persian medicine [TPM] advices) and control group
      (only lactulose) through a block randomization. Weekly follow-up was done for 1
      month for both groups. RESULTS: After the intervention, the frequency of bowel
      habit increased significantly in patients of both groups (P = 0.001), and the
      frequency of hard stool defecation, sensation of painful defecation, sensation of
      incomplete evacuation, sensation of anorectal obstruction, and manual maneuver
      for evacuation were decreased significantly in patients of both groups (P < 0.001
      for all comparisons and 0.025 for manual maneuver). However, the only significant
      difference between the two groups was more reduction in the sensation of painful
      defecation in the lactulose group versus lactulose plus TPM advices (P = 0.014).
      CONCLUSIONS: Based on the pilot study, no significant difference was shown
      between TPM with lactulose and lactulose only in the management of chronic
      functional constipation. However, the easy recommendations of TPM can be useful
      in improving chronic constipation.

PMID- 28757928
TI  - Assessing the Need for Routine Screening for Mycoplasma genitalium in the Low
      risk Female Population: A Prevalence and Co-infection Study on Women from
      Croatia.
AB  - BACKGROUND: There is an ongoing debate regarding possible cost and benefits, but
      also harm of universal screening for the emerging sexually transmitted pathogen
      Mycoplasma genitalium. METHODS: From the initial pool of 8665 samples that were
      tested, a subset of Chlamydia trachomatis-positive and randomly selected C.
      trachomatis-negative cervical swabs were further interrogated for M. genitalium
      by real-time polymerase chain reaction, using a 224 bp long fragment of the
      glyceraldehyde-3-phosphate dehydrogenase gene. RESULTS: M. genitalium was
      detected in 4.8% of C. trachomatis-positive samples and none of C. trachomatis
      negative samples. Accordingly, a significant association was shown between M.
      genitalium and C. trachomatis (P < 0.01), but also between M. genitalium and
      Mycoplasma hominis infection (P < 0.01). CONCLUSIONS: Based on the results,
      routine screening is recommended only for women with one or more identified risk
      factors. Moreover, younger age does not represent an appropriate
      inclusion/exclusion criterion for M. genitalium testing in the low-risk female
      population.

PMID- 28757929
TI  - Driving Behavior among Different Groups of Iranian Drivers Based on Driver Coping
      Styles.
AB  - BACKGROUND: This study aimed to assess driving behavior of Iranian drivers based
      on their coping styles (problem-oriented, emotion-oriented, and avoiding).
      METHODS: This study was conducted on 610 drivers divided into four different
      groups. The drivers' behaviors and coping styles were evaluated using driver
      behavior questionnaire (DBQ) and coping inventory for stressful situations.
      RESULTS: The results showed a significant difference among the three coping
      styles regarding the mean scores of DBQ dimensions (P < 0.001). In addition, the
      emotion-oriented drivers obtained higher mean scores compared to those with other
      coping styles. CONCLUSIONS: It can be concluded that emotion-oriented drivers
      were more susceptible to crashes compared to those with problem-solving and
      avoidance coping styles.

PMID- 28757930
TI  - Efficacy of a new coating of implant-abutment connections in reducing bacterial
      loading: an in vitro study.
AB  - BACKGROUND: Titanium is the gold standard for dental implants, since it has
      demonstrated excellent biocompatibility and osseointegration properties. The rate
      of osseointegration is however affected by the surface morphology and peri
      implant infections may affect fixture and the long-term osseointegration outcome.
      Thus chemical composition of a coating at the implant-abutment junction (IAJ)
      surface is expected to play a key role in preventing bacterial infection.
      PURPOSE: In the present study a new antimicrobial polysiloxane coating
      functionalized with chlorexidine digluconate (PXT) has been tested in an in vitro
      model. MATERIALS AND METHODS: Twenty implants were coated in the internal chamber
      with PXT and twenty were used as controls. RESULTS AND CONCLUSIONS: Ten of the
      coated implants, preliminarily tested against Gram positive and negative bacteria
      and fungi, showed a complete inactivation of the microbial species after a 15 min
      contact. On the remaining ten treated implants a series of microbiological tests
      and PCR analysis, after contamination of the implant external medium, in which
      the implant have been immersed, with genetic modified Tannerella forsythia (TF)
      and Porphyromonas Gingivalis (PG), leads to the conclusion that the coating is
      capable of inactivating the microbial species penetrating the internal of the
      implant through the implant abutment junction.

PMID- 28757931
TI  - New insights in orofacial cleft: epidemiological and genetic studies on italian
      samples.
AB  - Cleft of the lip and/or palate (CL+/-P) is the most common congenital
      craniofacial anomaly affecting around 1 in 700 live births worldwide. Clefts of
      the human face can be classified anatomically as cleft lip only (CL), cleft
      palate only (CP), cleft lip and palate (CLP) or a combined group of cleft lip
      with or without cleft palate (CL+/-P), based on differences in embryologic
      development. CL+/-P has a genetic base and several linkage and association
      analyses have been performed in order to obtain important information about the
      role of candidate genes in its onset; not less important are gene-environment
      interactions that play an increasing role in its aetiology. In CL+/-P, several
      loci have been seen associated with the malformation, and, in some cases, a
      specific gene mapping in a locus has also been identified as susceptibility
      factor. In CP, one gene has been found, but many more are probably involved. In
      this short review the genetic studies carried out on CL+/-P, and the interaction
      with environmental factors (alcohol, smoking, drugs) are discussed.

PMID- 28757932
TI  - Genetic susceptibility and periodontal disease: a retrospective study on a large
      italian sample.
AB  - BACKGROUND: Periodontal disease (PD) is a multifactorial illness in which
      environment and host interact. The genetic component plays a key role in the
      onset of PD. In fact the genetic compound can modulate the inflammation of the
      mucous membranes and the loss of alveolar bone. The genetics of PD is not well
      understood. Previous studies suggest a strong association between PD occurrence
      and individual genetic profile. The role of genetic susceptibility could impact
      on the clinical manifestations of PD, and consequently on prevention and therapy.
      MATERIALS AND METHODS: Genetic polymorphisms of VRD, IL6 and IL10 were
      investigated in Italian adults affected by PD. 571 cases classified according the
      criteria of the American Academy of Periodontology were included. All patients
      were Italian coming from three areas according to italian institute of statistics
      (ISTAT) (www.istat.it/it/archivio/regioni). The sample comprised 379 patients
      from North (66%), 152 from Central (26%) and 40 of South (8%). RESULTS: No
      significant differences were found among allele distribution. CONCLUSION: Chronic
      PD is a complex disease caused by a combination of genetic susceptibility,
      patients habits (oral hygiene, smoking, alcohol consumption) and oral pathogens.
      In our report no differences were detected among three Italian regions in allele
      distribution.

PMID- 28757933
TI  - Prevalence of periodontal pathogens among italian patients with chronic
      periodontitis: a retrospective study on 2992 patients.
AB  - PURPOSE: The aim of the present study was to evaluate the prevalence of some
      periodontal pathogens in Italian adults with chronic periodontitis. MATERIALS AND
      METHODS: The sample consisted of 2992 patients with a clinical diagnosis of
      chronic periodontitis, based on the criteria of the American Academy of
      Periodontology, sampled in the period 2013-2016: 2108 patients were from
      Northern, 690 from Central and 194 from Southern Italy. Porphyromonas gengivalis,
      Treponema denticola, and Tannerella forsythia were investigated in all patients
      of the present study, while Campylobacter rectus, Fusobacterium nucleatum and
      Aggregatibacter actinomycetemcomitans only in 2514 (84%) patients. Subgingival
      plaque samples of the four sites of greatest probing depth in each patient were
      used to obtain subgingival microbiota and then processed by quantitative
      polymerase chain reaction. RESULTS: Periodontal pathogens had the following
      presence respect to all amount of patients: Aggregatibacter actinomycetemcomitans
      16.1%, Campylobacter rectus 73.4%, Fusobacterium nucleatum 93.8%, Porphyromonas
      gengivalis 65.5%, Treponema denticola 66.4%, and Tannerella forsythia 72.7%.
      There are no significant statistical differences among geographic areas both for
      the total bacterial and the single species except for T. Denticola and C. Rectus,
      which prevalence was significantly higher in Southern Italy (P value <.05). The
      other investigated species were equally distributed among different regions. A.
      actinomycetemcomitans was the rarer species detected in this study, while F.
      nucleatum was the commonest. No differences among areas where observed as regard
      of the mean bacterial load except for F. Nucleatum whose prevalence in Northern
      Italy was lower then both in Central and Southern Italy (P value <.05).
      CONCLUSIONS: The results of our study didn't show different geographic
      distribution of periodontal pathogens among Italian population of the three areas
      investigated. The homogeneity of the results could be related to genetic and
      environmental factors.

PMID- 28757934
TI  - Applications of biomaterials for bone augmentation of jaws: clinical outcomes and
      in vitro studies.
AB  - Partially or totally edentulous jaws frequently undergoes from moderate to severe
      bone atrophy with problems of prosthetic rehabilitation. The inability to make a
      prosthetic rehabilitation on implants may led to the use of a partial or total
      removable denture with difficulties in eating and speech, ulcerations of the oral
      mucosa and loss of facial vertical dimension. These problems may be solved
      performing bone augmentation procedures. Bone grafts and distraction osteogenesis
      brought implant dentistry from an experimental practice to become a consolidate
      dental procedure. Bone grafts, in particular, are currently a valuable treatment
      modality for the prosthetic rehabilitation. Numerous biomaterials have been
      developed for the rehabilitation of partially or totally edentulous jaws with
      fixed or removable dentures. The aim of this paper is to describe biomaterials
      for bone augmentation. Biomaterials are gradually resorbed by the osteoclasts and
      replaced by new bone formed through osteoblastic activity. Many biomaterials have
      been studied, but the most common are as follows: Allogro(r), Algipore(r),
      Osteobiol(r), Peptide-15, Engipore(r), Medpore(r), Osteoplant(r), Calcium
      sulfate, Perioglass(r), Bio-Oss(r), Calcium phosphate.

PMID- 28757936
TI  - Three-point bending test simulation on implant fpds with a bio-faithful model.
AB  - AIM OF THE STUDY: It is well known by previous important studies that mandible
      flexes during different jaw movements. According to this assumption it is very
      important to know how implant supported fixed partial dentures could restrict
      mandibular movements and, could lead to excess strain accumulation that could
      modify the resolution of implant treatment. The aim of our project is to create a
      bio-faithful model able to recreate mandibular movements, during three point
      bending test methods of (FIXED -PARTIAL -DENTURES) FPDs, to avoid a not flexible
      metal base, where models' properties doesn't allow to obtain a bio-faithful
      simulation during testing phases. MATERIALS AND METHODS: 2 implants (premium
      Sweden and Martina(r)) were embedded in mandible resin section to mimic
      osteointegrated implants in premolar and molar areas, in order to recreate a
      Kennedy Class II configuration. Our mandible test simulator was creating
      according to the measurement obtained according to the study of Schwartz-Dabney
      and Dechow (2002). Sample so created is tested with testing machine (Instron
      5566(r), UK) adopting the three point bending mechanical tests configuration.
      DISCUSSION AND CONCLUSION: We can admit that oral cavity is a bio-dynamic system,
      where different variables incurr, so it's very important that experimental
      conditions simulate clinical environment. Experimentation should be based on the
      correlation between the failure mechanisms exhibited for in vitro samples and
      those observed in fractured clinical prostheses made of the same composition and
      processing conditions. A bio-faithful model could reduce this wide range between
      in vitro and in vivo study experimentation.

PMID- 28757935
TI  - Cleft palate only: current concepts.
AB  - Cleft palate only (CPO) is one of the most common congenital malformations
      worldwide. The etiopathogenesis of CPO is not completely understood.
      Environmental factors, such as smoking, alcohol consumption, intake of drugs
      during pregnancy, advanced paternal age, have been demonstrated to be a risk of
      CPO, but conflicting results have also been published. Insufficient intake of
      folic acid during the pregnancy has been suggested to increase the risk for CPO.
      The demonstrated risk for siblings and the higher risk for monozygotic twins
      suggest a genetic etiopathogenesis for CPO. In some cases of CPO a prevalent mode
      of inheritance has been reported, but oligogenic models with reduced penetrance,
      and the risk related to environmental factors have also been proved. One of the
      first manifestations associated with CPO is difficulty with feeding. Aerophagia
      is a problem in these infants with CPO and requires more frequent burping and
      slower feeding. The inability to generate intraoral breath pressure due to nasal
      air emission in CPO children frequently manifests as articulation difficulties,
      particularly consonant weakness, and unintelligible speech. Hearing disorders are
      prevalent among individuals with CPO, as a result of chronic otitis media with
      effusion due to eustachian tube dysfunction. A multidisciplinary team is
      essential to manage the many aspects of CPO. In treating CPO, the reconstructive
      surgeon works in cooperation with otolaryngologists, dentists and orthodontists,
      speech pathologists, audiologists, geneticists, psychiatrists, maxillofacial
      surgeons, social workers, and prosthodontists. CPO can be considered a
      genetically complex disease, but new knowledge and new therapeutic approaches
      have greatly improved the quality of life of these children. Prenatal diagnosis
      is an important step in the treatment of this disease.

PMID- 28757937
TI  - A comparative study of antibacterial and anti-inflammatory effects of mouthrinse
      containing tea tree oil.
AB  - : The study evaluated the antibacterial and anti-inflammatory efficacy,
      domiciliary oral hygiene, of a mouthrinse containing Tea Tree Oil (TTO) comparing
      it with two mouthrinses containing chlorhexidine 0,12% respectively and essential
      oils, and a placebo. MATERIALS AND METHODS: A pilot study, randomized 4 * 4,
      controlled, cross-over, double-blind. 16 subjects with gingivitis (7 males and 9
      females) aged 21-37 years, were randomly divided into four groups based on
      mouthwash that had to be used for domiciliary oral hygiene: mouthwash with
      essential oils, mouthwash with chlorhexidine 0,12 %, mouthwash containig tea tree
      oil and mouthwash placebo. Clinical evaluation was performed by: Full Mouth
      Plaque Score (FMPS), Full Mouth Bleeding Score (FMBS), Gingival Index (GI),
      discolorations, language examination and alteration of taste. The data were
      recorded before and 2 weeks after treatment. RESULTS: Statistical analysis shows
      that treatments with tea tree oil, essential oils and chlorhexidine are
      effective. Comparing treatments should be noted that the tea tree oil gives a
      greater improvement in the GI and FMBS, while it is the least effective in the
      control of bacterial plaque. CONCLUSION: Although further studies are needed, the
      anti-inflammatory properties of the mouthwash made from TTO would seem to be a
      valuable non-toxic adjunct in the management of gingivitis.

PMID- 28757938
TI  - Postextraction computer-guided implant surgery in partially edentate patients
      with metal restorations: a case report.
AB  - OBJECTIVES: The aim of the present study was to describe a postextraction,
      computer-guided protocol for implant-prosthetic rehabilitations in partially
      edentate patients with metal restorations. METHODS: A 60-year-old man with a
      loose FDP (fixed dental prosthesis) in the first quadrant was selected for a
      postextraction computer guided implantology according with the 2-piece
      radiographic template protocol. A two components radiographic template was
      produced, with the teeth setup portion based on the wax-up. CBCT (cone beam
      computed tomography) scans of the patient, wearing the base portion of the
      radiographic template and of the assembled radiographic template alone, were
      accomplished. The CBCT volume were imported in a dedicated software
      (NobelClinician, Nobel-Biocare, Kloten, Switzerland) and a surgical template was
      produced from the digital planning. The surgery was performed with a flap
      approach, as a bone regeneration procedure was carried out. A delayed loading
      protocol was chosen to allow a healing free of masticatory stress. A mobile
      partial denture was delivered to the patient to grant function and social life
      until the delivery of the definitive FDP. RESULTS: The surgery was performed
      rapidly and free of obstacles. A good primary stability of the implants was
      achieved. The patient referred an acceptable postoperative pain and swelling.
      CONCLUSIONS: The 2-piece radiographic template protocol was evaluated as smooth,
      complication-free and suitable for patients who want to maintain their teeth
      until the day of implant surgery. A good command of the computer-guided software
      as well as a comprehensive learning curve in computer-guided implantology is
      necessary to obtain predictable results.

PMID- 28757939
TI  - Correlation between parodontal indexes and orthodontic retainers: prospective
      study in a group of 16 patients.
AB  - PURPOSE: Fixed retainers are used to stabilize dental elements after orthodontic
      treatment. Being it a permanent treatment, it is necessary to instruct patients
      about a constant and continuous monitoring of their periodontal conditions and a
      correct oral hygiene. The aim of this study was to highlight the possible adverse
      effects of bonded retainers on parameters correlated to the health conditions of
      periodontal tissues. MATERIALS AND METHODS: We selected 16 patients, under
      treatment in the Orthodontics Department of University of Bari Dental School, who
      had undergone a lingual retainer insertion at the end of the orthodontic
      treatment. The patients were then divided into two groups (Control Group and
      Study Group) and monitored for 3 and 36 months, respectively. The following
      indexes were taken into consideration: gingival index (GI), plaque index (PI) and
      the presence of calculus (Calculus Index, CI), the probing depth and the presence
      of gingival recession on the six inferior frontal dental elements. RESULTS: After
      the observation was carried out, any of the patients showed periodontal sockets
      and gingival recession. In the Study Group, only 1 patient had a PI score=3, the
      7 left had scores between 0.66 and 2.83. In the Control Group, one patient had
      score=0, the other ones showed values between 0.5 and 1.66. The mean GI in the
      Study Group peaked at a score of 2.83, the minimum was 0.66; whereas in the
      Control Group the maximum value was 2 and the minimum 0.66. The CI in the Group
      Study was between 1 and 2. In the Control Group it was absent in only 1 patient,
      whereas in the remaining 7, it had a value between 0.3 and 1. The clinical data
      were studied by means of the Wilcoxon test. We found a statistically significant
      difference for what concerns the Plaque Indexes (PI) (P>0.05) and Calculus
      Indexes (CI) (P>0.1) in both groups, with higher scores in the Study Group,
      having retainers for 36 months. Any statistically significant difference was
      calculated for the GI. CONCLUSIONS: We can therefore conclude that patients with
      lingual retainers need periodontal hygiene and treatment as to prevent, in the
      course of time, periodontal damages non-detectable in short-term.

PMID- 28757940
TI  - Core-shell structured phosphorescent nanoparticles for detection of exogenous and
      endogenous hypochlorite in live cells via ratiometric imaging and
      photoluminescence lifetime imaging microscopy.
AB  - We report a ratiometric phosphorescence sensory system for hypochlorite (ClO-)
      based on core-shell structured silica nanoparticles. Two phosphorescent
      iridium(iii) complexes were immobilised in the inner solid core and outer
      mesoporous layer of the nanoparticles, respectively. The former is insensitive to
      ClO- and thus serves as an internal standard to increase the accuracy and
      precision, while the latter exhibits a specific and significant luminogenic
      response to ClO-, providing high selectivity and sensitivity. Upon exposure to
      ClO-, the nanoparticles display a sharp luminescence colour change from blue to
      red. Additionally, intracellular detection of exogenous and endogenous ClO- has
      been demonstrated via ratiometric imaging and photoluminescence lifetime imaging
      microscopy. Compared to intensity-based sensing, ratiometric and lifetime-based
      measurements are independent of the probe concentration and are thus less
      affected by external influences, especially in intracellular applications.

PMID- 28757941
TI  - Harnessing selenocysteine reactivity for oxidative protein folding.
AB  - Although oxidative folding of disulfide-rich proteins is often sluggish, this
      process can be significantly enhanced by targeted replacement of cysteines with
      selenocysteines. In this study, we examined the effects of a selenosulfide and
      native versus nonnative diselenides on the folding rates and mechanism of bovine
      pancreatic trypsin inhibitor. Our results show that such sulfur-to-selenium
      substitutions alter the distribution of key folding intermediates and enhance
      their rates of interconversion in a context-dependent manner.

PMID- 28757942
TI  - 2,2'-Bipyridyl formation from 2-arylpyridines through bimetallic diyttrium
      intermediate.
AB  - An alkylyttrium complex supported by an N,N'-bis(2,6
      diisopropylphenyl)ethylenediamido ligand, (ArNCH2CH2NAr)Y(CH2SiMe3)(THF)2 (1, Ar
      = 2,6- i Pr2C6H3), activated an ortho-phenyl C-H bond of 2-phenylpyridine (2a) to
      form a (2-pyridylphenyl)yttrium complex (3a) containing a five-membered
      metallacycle. Subsequently, a unique C(sp2)-C(sp2) coupling of 2-phenylpyridine
      proceeded through a bimetallic yttrium intermediate, derived from an
      intramolecular shift of the yttrium center to an ortho-position of the pyridine
      ring in 3a, to yield a bimetallic yttrium complex (4a) bridged by two-electron
      reduced 6,6'-diphenyl-2,2'-bipyridyl. Aryl substituents at the ortho-position of
      the pyridine ring were key in order to destabilize the MU,kappa2-(C,N)
      pyridyldiyttrium intermediate prior to the C(sp2)-C(sp2) bond formation.

PMID- 28757943
TI  - An iridium(iii)-based irreversible protein-protein interaction inhibitor of BRD4
      as a potent anticancer agent.
AB  - Bromodomain-containing protein 4 (BRD4) has recently emerged as an attractive
      epigenetic target for anticancer therapy. In this study, an iridium(iii) complex
      is reported as the first metal-based, irreversible inhibitor of BRD4. Complex 1a
      is able to antagonize the BRD4-acetylated histone protein-protein interaction
      (PPI) in vitro, and to bind BRD4 and down-regulate c-myc oncogenic expression in
      cellulo. Chromatin immunoprecipitation (ChIP) analysis revealed that 1a could
      modulate the interaction between BRD4 and chromatin in melanoma cells, particular
      at the MYC promoter. Finally, the complex showed potent activity against melanoma
      xenografts in an in vivo mouse model. To our knowledge, this is the first report
      of a Group 9 metal complex inhibiting the PPI of a member of the bromodomain and
      extraterminal domain (BET) family. We envision that complex 1a may serve as a
      useful scaffold for the development of more potent epigenetic agents against
      cancers such as melanoma.

PMID- 28757944
TI  - Exceptional time response, stability and selectivity in doubly-activated phenyl
      selenium-based glutathione-selective platform.
AB  - A phenyl-selenium-substituted coumarin probe was synthesized for the purpose of
      achieving highly selective and extremely rapid detection of glutathione (GSH)
      over cysteine (Cys)/homocysteine (Hcy) without background fluorescence. The
      fluorescence intensity of the probe with GSH shows a ~100-fold fluorescent
      enhancement compared with the signal generated for other closely related amino
      acids, including Cys and Hcy. Importantly, the substitution reaction with the
      sulfhydryl group of GSH at the 4-position of the probe, which is doubly-activated
      by two carbonyl groups, occurs extremely fast, showing subsecond maximum
      fluorescence intensity attainment; equilibrium was reached within 100 ms (UV
      vis). The probe selectivity for GSH was confirmed in Hep3B cells by confocal
      microscopy imaging.

PMID- 28757945
TI  - Well-defined silica supported aluminum hydride: another step towards the utopian
      single site dream?
AB  - Reaction of triisobutylaluminum with SBA15700 at room temperature occurs by two
      parallel pathways involving either silanol or siloxane bridges. It leads to the
      formation of a well-defined bipodal [( 0000000000000000000000000000000000
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      0000000000000000000000000000000000 SiO)2Al-CH2CH(CH3)2] 1a, silicon isobutyl [Si
      CH2CH(CH3)2] 1b and a silicon hydride [Si-H] 1c. Their structural identity was
      characterized by FT-IR and advanced solid-state NMR spectroscopies (1H, 13C,
      29Si, 27Al and 2D multiple quantum), elemental and gas phase analysis, and DFT
      calculations. The reaction involves the formation of a highly reactive monopodal
      intermediate: [SiO-Al-[CH2CH(CH3)2]2], with evolution of isobutane. This
      intermediate undergoes two parallel routes: transfer of either one isobutyl
      fragment or of one hydride to an adjacent silicon atom. Both processes occur by
      opening of a strained siloxane bridge, Si-O-Si but with two different mechanisms,
      showing that the reality of "single site" catalyst may be an utopia: DFT
      calculations indicate that isobutyl transfer occurs via a simple metathesis
      between the Al-isobutyl and O-Si bonds, while hydride transfer occurs via a two
      steps mechanism, the first one is a beta-H elimination to Al with elimination of
      isobutene, whereas the second is a metathesis step between the formed Al-H bond
      and a O-Si bond. Thermal treatment of 1a (at 250  degrees C) under high vacuum
      (10-5 mbar) generates Al-H through a beta-H elimination of isobutyl fragment.
      These supported well-defined Al-H which are highly stable with time, are tetra,
      penta and octa coordinated as demonstrated by IR and 27Al-1H J-HMQC NMR
      spectroscopy. All these observations indicate that surfaces atoms around the site
      of grafting play a considerable role in the reactivity of a single site system.

PMID- 28757946
TI  - A crystalline sponge based on dispersive forces suitable for X-ray structure
      determination of included molecular guests.
AB  - A crystalline porous material showing one-dimensional (1-D) rectangular
      micropores (12 * 9 A2) has been assembled from a semirigid macrocyclic tetraimine
      and EtOAc as the templating agent. The 1-D nature of the material is intrinsic to
      the conformationally rigid structure of a macrocyclic sub-unit bearing four
      cyclohexylidene residues. The multiple dispersive forces established among the
      aliphatic residues glutted the 1-D channels and provided thermal stability to the
      material at temperatures below 160  degrees C. Upon removal of the template, the
      structure of the empty solid exhibited permanent microporosity (SBET = 342 m2 g
      1). Being a true molecular sponge, the channel framework of this material allowed
      the inclusion of a variety of molecular sample guests without compromising its
      crystalline nature. Remarkably, this crystalline material enabled the structure
      determination by X-ray diffraction of the included molecules. Theoretical studies
      demonstrated the vital role played by the dispersive forces in the overall
      stabilization of the crystal packing.

PMID- 28757947
TI  - Tetraarylborate polymer networks as single-ion conducting solid electrolytes.
AB  - A new family of solid polymer electrolytes based upon anionic
      tetrakis(phenyl)borate tetrahedral nodes and linear bis-alkyne linkers is
      reported. Sonogashira polymerizations using tetrakis(4-iodophenyl)borate,
      tetrakis(4-iodo-2,3,5,6-tetrafluorophenyl)borate and tetrakis(4-bromo-2,3,5,6
      tetrafluorophenyl)borate delivered highly cross-linked polymer networks with both
      1,4-diethynylbeznene and a tri(ethylene glycol) substituted derivative. Promising
      initial conductivity metrics have been observed, including high room temperature
      conductivities (up to 2.7 * 10-4 S cm-1), moderate activation energies (0.25-0.28
      eV), and high lithium ion transport numbers (up to tLi+ = 0.93). Initial
      investigations into the effects of important materials parameters such as bulk
      morphology, porosity, fluorination, and other chemical modification, provide
      starting design parameters for further development of this new class of solid
      electrolytes.

PMID- 28757948
TI  - Reaction of a diaryldigermyne with ethylene.
AB  - Reaction of the stable digermyne BbtGe 0000000000000000000000000000000000
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      0000000000000000000000000000000000 GeBbt (Bbt = 2,6-[CH(SiMe3)2]2-4-[C(SiMe3)3]
      C6H2) with ethylene initially afforded the corresponding 1,2-digermacyclobutene.
      Depending on the reaction conditions applied, further reaction of this 1,2
      digermacyclobutene with ethylene furnished two different reaction products: a 1,4
      digermabicyclo[2.2.0]hexane or a bis(germiranyl)ethane. Combined experimental and
      theoretical results suggested that the 1,4-digermabicyclo[2.2.0]hexane and the
      bis(germiranyl)ethane are the thermodynamic and kinetic reaction products,
      respectively. A reaction mechanism in agreement with these results was proposed.

PMID- 28757949
TI  - Addition of aluminium, zinc and magnesium hydrides to rhodium(iii).
AB  - We report the addition of M-H bonds (M = Al, Zn, Mg) to a Rh(iii) intermediate
      generated from the reductive elimination of triethylsilane from
      [Cp*Rh(H)2(SiEt3)2]. A series of new heterobimetallic complexes possessing Rh-M
      bonds have been isolated and characterised by a number of spectroscopic (1H,
      29Si, 13C, 103Rh NMR, infrared, and X-ray diffraction) and computational
      techniques (NBO and QTAIM analysis). Experimental and computational data are
      consistent with cleavage of the M-H bond upon addition to rhodium with formation
      of new Rh-M and Rh-H bonds. Upon photolysis the Al analogue of this series
      undergoes a further elimination reaction producing triethylsilane and a highly
      unusual Rh2Al2H4 containing cluster proposed to contain an Al(i) bridging ligand.

PMID- 28757950
TI  - Detection of 5-methylcytosine and 5-hydroxymethylcytosine in DNA via host-guest
      interactions inside alpha-hemolysin nanopores.
AB  - Cytosine methylation and hydroxymethylation are both important epigenetic
      modifications of DNA in mammalian cells. Therefore, profiling DNA
      (hydroxy)methylation across the genome is vital for understanding their roles in
      gene regulation. Here, we report a nanopore-based approach for quick and reliable
      detection of 5-methylcytosine and 5-hydroxymethylcytosine in DNA at the single
      molecule level. The single-stranded DNA containing 5-methylcytosine or 5
      hydroxymethylcytosine was first selectively modified on the epigenetic base to
      attach a host-guest complex. Threading of the modified DNA molecules through
      alpha-hemolysin nanopores causes unbinding of the host-guest complex and
      generates highly characteristic current signatures. Statistical analysis of the
      signature events affords quantitative information about 5-methylcytosine and 5
      hydroxymethylcytosine in DNA. Our results suggest that other DNA modifications
      could also be detected with the developed method. Furthermore, we anticipate our
      nanopore sensing strategy to be generally useful in biochemical analysis and to
      find applications in the early diagnosis of diseases.

PMID- 28757951
TI  - Mechanistic insights into the reductive dehydroxylation pathway for the
      biosynthesis of isoprenoids promoted by the IspH enzyme.
AB  - Here, we report an integrated quantum mechanics/molecular mechanics (QM/MM) study
      of the bio-organometallic reaction pathway of the 2H+/2e- reduction of (E)-4
      hydroxy-3-methylbut-2-enyl pyrophosphate (HMBPP) into the so called universal
      terpenoid precursors isopentenyl pyrophosphate (IPP) and dimethylallyl
      pyrophosphate (DMAPP), promoted by the IspH enzyme. Our results support the
      viability of the bio-organometallic pathway through rotation of the OH group of
      HMBPP away from the [Fe4S4] cluster at the core of the catalytic site, to become
      engaged in a H-bond with Glu126. This rotation is synchronous with pi
      coordination of the C2 0000000000000000000000000000000000
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      0000000000000000000000000000000000 C3 double bond of HMBPP to the apical Fe atom
      of the [Fe4S4] cluster. Dehydroxylation of HMBPP is triggered by a proton
      transfer from Glu126 to the OH group of HMBPP. The reaction pathway is completed
      by competitive proton transfer from the terminal phosphate group to the C2 or C4
      atom of HMBPP.

PMID- 28757952
TI  - Carbon nitride-TiO2 hybrid modified with hydrogenase for visible light driven
      hydrogen production.
AB  - A system consisting of a [NiFeSe]-hydrogenase (H2ase) grafted on the surface of a
      TiO2 nanoparticle modified with polyheptazine carbon nitride polymer, melon (CN x
      ) is reported. This semi-biological assembly shows a turnover number (TON) of
      more than 5.8 * 105 mol H2 (mol H2ase)-1 after 72 h in a sacrificial electron
      donor solution at pH 6 during solar AM 1.5 G irradiation. An external quantum
      efficiency up to 4.8% for photon-to-hydrogen conversion was achieved under
      irradiation with monochromatic light. The CN x -TiO2-H2ase construct was also
      active under UV-free solar light irradiation (lambda > 420 nm), where it showed a
      substantially higher activity than TiO2-H2ase and CN x -H2ase due, in part, to
      the formation of a CN x -TiO2 charge transfer complex and highly productive
      electron transfer to the H2ase. The CN x -TiO2-H2ase system sets a new benchmark
      for photocatalytic H2 production with a H2ase immobilised on a noble- and toxic
      metal free light absorber in terms of visible light utilisation and stability.

PMID- 28757953
TI  - Mixed valence mono- and hetero-metallic grid catenanes.
AB  - Here, we report on the multicomponent self-assembly and single crystal X-ray
      diffraction study of a series of three interlocked mixed valence mono- and hetero
      metallic [2]-catenanes made of [2 * 2] metallo-grids. They show unique structural
      features and highlight the essential roles of both the Cu(ii)/Cu(i) pair and of
      the conformationally adaptable organic ligands for achieving catenation of grids.

PMID- 28757954
TI  - Constructing real-time, wash-free, and reiterative sensors for cell surface
      proteins using binding-induced dynamic DNA assembly.
AB  - Cell surface proteins are an important class of biomarkers for fundamental
      biological research and for disease diagnostics and treatment. In this
      communication, we report a universal strategy to construct sensors that can
      achieve rapid imaging of cell surface proteins without any separation by using
      binding-induced dynamic DNA assembly. As a proof-of-principle, we developed a
      real-time and wash-free sensor for an important breast cancer biomarker, human
      epidermal growth factor receptor-2 (HER2). We then demonstrated that this sensor
      could be used for imaging and sensing HER2 on both fixed and live breast cancer
      cells. Additionally, we have also incorporated toehold-mediated DNA strand
      displacement reactions into the HER2 sensor, which allows for reiterating
      (switching on/off) fluorescence signals for HER2 from breast cancer cells in real
      time.

PMID- 28757955
TI  - Light-driven bending of diarylethene mixed crystals.
AB  - Mixed crystals composed of 1,2-bis(2-methyl-5-(p-methoxyphenyl)-3
      thienyl)perfluorocyclopentene (1a) and 1,2-bis(5-methyl-2-(p-methoxyphenyl)-4
      thiazolyl)perfluorocyclopentene (2a) were prepared, and their photochromic as
      well as light-driven bending performance was studied to reveal how shape changes
      of individual molecules cause the bending response. 1a and 2a molecules, having
      similar geometrical structures, randomly mix with each other in a single crystal.
      The absorption spectra of the closed-ring isomers 1b and 2b were, however,
      distinctly different. The difference of the spectra made it possible to
      discriminate the cycloreversion reactions of 1b and 2b in the mixed crystals by
      irradiation with 750 nm light. The bending response of the mixed crystals by the
      selective photoisomerization revealed that the local shape change of each
      molecule is additively linked to the macroscopic deformation of the crystals.

PMID- 28757956
TI  - A highly convergent synthesis of the C1-C31 polyol domain of amphidinol 3
      featuring a TST-RCM reaction: confirmation of the revised relative
      stereochemistry.
AB  - The concise enantioselective synthesis of the revised C1-C31 fragment of the
      polyketide amphidinol 3 was accomplished in 16 steps and 12.8% overall yield.
      Salient features of the strategy include chemoselective Weinreb amide coupling
      and concomitant CBS reduction for the preparation of the C1-C15 tris-syn-1,5-diol
      motif and a temporary silicon-tethered ring-closing metathesis (TST-RCM) reaction
      in combination with a diastereoselective hydroboration for the construction of
      the C16-C31 polypropionate fragment. The union of the fragments was accomplished
      by a regioselective ring-opening of the terminal epoxide with a phenyl sulfone
      stabilized carbanion, which upon reduction and deprotection permits a comparison
      of the relative configuration with the natural product.

PMID- 28757957
TI  - Pt nanohelices with highly ordered horizontal pore channels as enhanced
      photothermal materials.
AB  - Recent studies have further demonstrated that the conjugation of noble metal
      helical nanostructures could alter their optical and catalytic activities.
      However, the intrinsic isotropic crystal growth of Pt makes the synthesis of high
      quality Pt NCs with unique porous or branched nanostructures difficult. In this
      work, a new, powerful capping agent, N,N-dimethyloctadecylammonium bromide
      acetate sodium, was synthesized and used to coordinate Pt ions, slowing down the
      reaction rate. As a result, in aqueous solution, Pt nanohelices with highly
      ordered horizontal pore channels were successfully fabricated. Importantly, the
      Pt nanohelices were composed of several sub-2 nm Pt nanowires coiled together
      around a central point. The as-obtained samples exhibited enhanced photothermal
      properties compared with the classic Pt nanoparticles.

PMID- 28757958
TI  - Bridging cells of three colors with two bio-orthogonal click reactions.
AB  - Cell-cell interactions play a crucial role in the development and function of
      multicellular organisms. To study cell-cell interactions in vitro, it is a big
      challenge for researchers to artificially build up cell junctions to bridge
      different types of cells for this purpose. Herein, by employing two orthogonal
      click reactions, we rationally designed four click reagents Mal-CBT, Mal-Cys, Mal
      Alkyne, and Mal-N3 and successfully applied them to bridge cells of three colors.
      Orthogonality between these two click reactions was validated in solution and
      characterized with HPLC and ESI-MS analyses. After modifications of fluorescent
      protein-expressing prokaryotic Escherichia coli (E. coli) cells (or eukaryotic
      HEK 293T cells) of three colors with the reagents Mal-Cys, Mal-CBT and Mal
      Alkyne, or Mal-N3 , the cells were sequentially bridged. The HEK 293T cells
      showed a higher efficiency of cell bridging than the E. coli cells. Finally,
      using optical tweezers, we quantitatively measured the bridging probability
      between Mal-Cys-modified and Mal-CBT-modified HEK 293 cells, as well as the
      rupture force between two bridged cells. We found that the CBT-Cys click reaction
      markedly improved the efficiency of cell bridging and the rupture force between
      two bridged cells was measured to be 153.8 pN at a force-loading rate of 49 pN s
      1. Our results demonstrate that it is possible to use two (or n) orthogonal click
      reactions to bridge three (or n + 1) types of cells. Taking the biological
      importance of cell junctions into consideration, we anticipate that our method of
      bridging three types of cells with two bio-orthogonal click reactions will be a
      useful tool for biologists to study cell-cell interactions with more convenience
      and efficiency.

PMID- 28757959
TI  - Photoresponsive immunomagnetic nanocarrier for capture and release of rare
      circulating tumor cells.
AB  - Isolation, release and culture of rare circulating tumor cells (CTCs) may, if
      implemented, promote the progress of individualized anti-tumor therapies. To
      realize the release of CTCs without disruption of their viability for further
      culture and analysis, we designed an effective photocontrolled CTC
      capture/release system by combination of photochemistry and immunomagnetic
      separation. 7-Aminocoumarin was synthesized as the phototrigger to bridge the
      connection between the anti-EpCAM antibody and the magnetic beads. The coumarin
      moieties produced cleavage of a C-O bond under both ultraviolet (UV) and near
      infrared (NIR) light illumination, breaking the bridge and releasing CTCs from
      the immunomagnetic beads. Compared with conventional immunomagnetic separation
      systems, the negative influence of absorbed immunomagnetic beads on further CTCs
      culture and analysis was effectively eliminated. The system can specifically
      recognize 102 MCF-7 cells in 1 mL of human whole blood samples with 90%
      efficiency and 85% purity. Under the irradiation of UV and NIR light, 73 +/- 4%
      and 52 +/- 6% of captured cells were released with a viability of 90% and 97%,
      respectively. Furthermore, this technique has been used to detect CTCs from whole
      blood of cancer patients with high purity. This study demonstrates that the
      photochemical-based immunomagnetic separation method for isolating, releasing and
      culturing CTCs from clinic patients may provide new opportunities for cancer
      diagnosis and personalized therapy.

PMID- 28757960
TI  - Structural basis of head to head polyketide fusion by CorB.
AB  - Corallopyronin A is a polyketide derived from the myxobacterium Corallococcus
      coralloides with potent antibiotic features. The gene cluster responsible for the
      biosynthesis of corallopyronin A has been described recently, and it was proposed
      that CorB acts as a ketosynthase to interconnect two polyketide chains in a rare
      head-to-head condensation reaction. We determined the structure of CorB, the
      interconnecting polyketide synthase, to high resolution and found that CorB
      displays a thiolase fold. Site-directed mutagenesis showed that the catalytic
      triad consisting of a cysteine, a histidine and an asparagine is crucial for
      catalysis, and that this triad shares similarities with the triad found in HMG
      CoA synthases. We synthesized a substrate mimic to derivatize purified CorB and
      confirmed substrate attachment by ESI-MS. Structural analysis of the complex
      yielded an electron density-based model for the polyketide chain and showed that
      the unusually wide, T-shaped active site is able to accommodate two polyketides
      simultaneously. Our structural analysis provides a platform for understanding the
      unusual head-to-head polyketide-interconnecting reaction catalyzed by CorB.

PMID- 28757962
TI  - Controllability of dynamic double helices: quantitative analysis of the inversion
      of a screw-sense preference upon complexation.
AB  - We describe a quantitative analysis of the complexation-induced inversion of a
      screw-sense preference based on a conformationally dynamic double-helix structure
      in a macrocycle. The macrocycle is composed of two twisting units
      (terephthalamide), which are spaced by two strands (1,3
      bis(phenylethynyl)benzene), and is designed to generate a double-helix structure
      through twisting about a C2 axis in a conrotatory manner. The attachment of
      chiral auxiliaries to the twisting units induces a helical preference for a
      particular sense of (M)- or (P)-helicity through the intramolecular transmission
      of chirality to dynamic double helices. The twisting unit can also act as a
      binding site for capturing a guest molecule, and, in a complexed state, the
      preferred screw sense of the dynamic double-helix structure is reversed to
      exhibit the contrary preference. We quantitatively monitored the complexation
      induced inversion of the screw-sense preference using 1H NMR spectroscopy, which
      enabled us to observe independently two species with (M)- or (P)-helicity in both
      the absence and presence of a guest molecule. Inversion of the screw-sense
      preference was induced upon complexation with an achiral guest as well as a
      chiral guest.

PMID- 28757961
TI  - Light driven mesoscale assembly of a coordination polymeric gelator into flowers
      and stars with distinct properties.
AB  - Control over the self-assembly process of porous organic-inorganic hybrids often
      leads to unprecedented polymorphism and properties. Herein we demonstrate how
      light can be a powerful tool to intervene in the kinetically controlled mesoscale
      self-assembly of a coordination polymeric gelator. Ultraviolet light induced
      coordination modulation via photoisomerisation of an azobenzene based
      dicarboxylate linker followed by aggregation mediated crystal growth resulted in
      two distinct morphological forms (flowers and stars), which show subtle
      differences in their physical properties.

PMID- 28757963
TI  - Thermally-responsive, nonflammable phosphonium ionic liquid electrolytes for
      lithium metal batteries: operating at 100 degrees celsius.
AB  - Rechargeable batteries such as Li ion/Li metal batteries are widely used in the
      electronics market but the chemical instability of the electrolyte limits their
      use in more demanding environmental conditions such as in automotive, oil
      exploration, or mining applications. In this study, a series of alkyl phosphonium
      ionic liquid electrolyte are described with high thermal stability and solubility
      for LiTFSI. A lithium metal battery (LMB) containing a tailored phosphonium ionic
      liquid/LiTFSI electrolyte operates at 100  degrees C with good specific
      capacities and cycling stability. Substantial capacity is maintained during 70
      cycles or 30 days. Instant on-off battery operation is realized via the
      significant temperature dependence of the electrolyte material, demonstrating the
      robustness and potential for use at high temperature.

PMID- 28757964
TI  - A cell-penetrating protein designed for bimodal fluorescence and magnetic
      resonance imaging.
AB  - Multimodal imaging is a highly desirable biomedical application since it can
      provide complementary information from each imaging modality. We propose a
      protein engineering-based strategy for the construction of a bimodal probe for
      fluorescence and magnetic resonance imaging. A recombinant protein was generated
      by the fusion of a supercharged green fluorescence protein (GFP36+) with a
      lanthanide-binding tag (dLBT) that can stably bind two Gd3+ ions. The GFP36+-dLBT
      fusion protein showed strong fluorescence and exhibited efficient contrast
      enhancement in magnetic resonance imaging. This protein probe improves the MR
      relaxation more efficiently than Gd-DTPA (gadopentetate dimeglumine). The
      superior cell-penetrating activity of GFP36+ allows the efficient cellular uptake
      of this fusion protein and it can thus be used as a cellular imaging probe. Dual
      imaging was conducted in vitro and in mice. This result indicates that the fusion
      of different functional domains is a feasible approach for making multi-modal
      imaging agents.

PMID- 28757965
TI  - Direct electrochemical detection of individual collisions between magnetic
      microbead/silver nanoparticle conjugates and a magnetized ultramicroelectrode.
AB  - Here, we report on the electrochemical detection of individual collisions between
      a conjugate consisting of silver nanoparticles (AgNPs) linked to conductive
      magnetic microbeads (cMMUBs) via DNA hybridization and a magnetized electrode.
      The important result is that the presence of the magnetic field increases the
      flux of the conjugate to the electrode surface, and this in turn increases the
      collision frequency and improves the limit of detection (20 aM). In addition, the
      magnitude of the charge associated with the collisions is greatly enhanced in the
      presence of the magnetic field. The integration of DNA into the detection
      protocol potentially provides a means for using electrochemical collisions for
      applications in biological and chemical sensing.

PMID- 28757966
TI  - Linear scaling relationships and volcano plots in homogeneous catalysis -
      revisiting the Suzuki reaction.
AB  - Linear free energy scaling relationships and volcano plots are common tools used
      to identify potential heterogeneous catalysts for myriad applications. Despite
      the striking simplicity and predictive power of volcano plots, they remain
      unknown in homogeneous catalysis. Here, we construct volcano plots to analyze a
      prototypical reaction from homogeneous catalysis, the Suzuki cross-coupling of
      olefins. Volcano plots succeed both in discriminating amongst different catalysts
      and reproducing experimentally known trends, which serves as validation of the
      model for this proof-of-principle example. These findings indicate that the
      combination of linear scaling relationships and volcano plots could serve as a
      valuable methodology for identifying homogeneous catalysts possessing a desired
      activity through a priori computational screening.

PMID- 28757967
TI  - Endogenous signalling control of cell adhesion by using aptamer functionalized
      biocompatible hydrogel.
AB  - Design of biological signal-responsive biomaterials is essential for controlling
      cell-cell and cell-matrix interactions. Herein, we developed a dynamic hydrogel
      to control cell adhesion with biological signals in a cellular microenvironment.
      The basic principle was based on using nucleic acid aptamer to recognize cell
      signalling and control the display of bioligands on the hydrogel. Not only
      exogenous signalling but also endogenous signalling secreted by surrounding cells
      could activate the dynamic scaffold and tune the cell adhesion state. Since
      diverse aptamers have been developed, our design can be extended to multiple
      biological inputs. The biochemical signal-responsive system will greatly enhance
      the understanding of complex biological processes as well as the ability to
      manipulate cellular behaviors.

PMID- 28757968
TI  - Connecting electrodes with light: one wire, many electrodes.
AB  - The requirement of a wire to each electrode is central to the design of any
      electronic device but can also be a major restriction. For example it entails
      space restrictions and rigid device architecture in multi-electrode devices. The
      finite space that is taken up by the array of electrical terminals and conductive
      pads also severely limits the achievable density of electrodes in the device.
      Here it is shown that a travelling light pointer can be used to form transient
      electrical connections anywhere on a monolithic semiconductor electrode that is
      fitted with a single peripheral electrical terminal. This is achieved using
      hydrogen terminated silicon electrodes that are modified with well-defined
      organic monolayers. It is shown that electrochemical information can be either
      read from or written onto these surfaces. Using this concept it is possible to
      form devices that are equivalent to a conventional electrode array but that do
      not require a predetermined architecture, and where each element of the array is
      temporally "connected" using light stimulus; a step change in capability for
      electrochemistry.

PMID- 28757969
TI  - Target-fueled DNA walker for highly selective miRNA detection.
AB  - Artificial DNA motifs as architectural scaffolds have been widely used to
      assemble a variety of nanoscale devices. Synthetic DNA nanostructures have
      accomplished mechanical switching in response to external stimuli, suggesting the
      promise of constructing a walking device that is being used in the field of
      biosensors. Here, we design a novel miRNA-responsive DNA walker biosensor based
      on strand displacement cascades and an enzymatic recycling cleavage strategy. By
      using miRNA as a driving force, the DNA walkers can be activated to move along
      the track and generate specific signals for let-7a with a high signal-to-noise
      ratio. This biosensor exhibits excellent analytical performance toward the
      sensing of let-7a with great specificity for resolving one nucleotide variation
      and a detection limit of 58 fM. Such an ultraselective sensor shows that DNA
      nanostructures have great potential in providing platforms for applications in
      the fields of biosensing, clinical diagnostics and environmental sample analysis.

PMID- 28757970
TI  - Stereoelectronic source of the anomalous stability of bis-peroxides.
AB  - The unusual stability of bis- and tris-peroxides contradicts the conventional
      wisdom - some of them can melt without decomposition at temperatures exceeding
      100  degrees C. In this work, we disclose a stabilizing stereoelectronic effect
      that two peroxide groups can exert on each other. This stabilization originates
      from strong anomeric nO -> sigma*CO interactions that are absent in mono
      peroxides but reintroduced in molecules where two peroxide moieties are separated
      by a CH2 group. Furthermore, such effects can be induced by other sigma-acceptors
      and amplified by structural constraints imposed by cyclic and bicyclic
      frameworks.

PMID- 28757971
TI  - Solar-microbial hybrid device based on oxygen-deficient niobium pentoxide anodes
      for sustainable hydrogen production.
AB  - Hydrogen gas is emerging as an attractive fuel with high energy density for the
      direction of energy resources in the future. Designing integrated devices based
      on a photoelectrochemical (PEC) cell and a microbial fuel cell (MFC) represents a
      promising strategy to produce hydrogen fuel at a low price. In this work, we
      demonstrate a new solar-microbial (PEC-MFC) hybrid device based on the oxygen
      deficient Nb2O5 nanoporous (Nb2O5-x NPs) anodes for sustainable hydrogen
      generation without external bias for the first time. Owing to the improved
      conductivity and porous structure, the as-prepared Nb2O5-x NPs film yields a
      remarkable photocurrent density of 0.9 mA cm-2 at 0.6 V (vs. SCE) in 1 M KOH
      aqueous solution under light irradiation, and can achieve a maximum power density
      of 1196 mW m-2 when used as an anode in a MFC device. More importantly, a solar
      microbial hybrid system by combining a PEC cell with a MFC is designed, in which
      the Nb2O5-x NPs electrodes function as both anodes. The as-fabricated PEC-MFC
      hybrid device can simultaneously realize electricity and hydrogen using organic
      matter and solar light at zero external bias. This novel design and attempt might
      provide guidance for other materials to convert and store energy.

PMID- 28757972
TI  - Pushing NMR sensitivity limits using dynamic nuclear polarization with closed
      loop cryogenic helium sample spinning.
AB  - We report a strategy to push the limits of solid-state NMR sensitivity far beyond
      its current state-of-the-art. The approach relies on the use of dynamic nuclear
      polarization and demonstrates unprecedented DNP enhancement factors for
      experiments performed at sample temperatures much lower than 100 K, and can
      translate into 6 orders of magnitude of experimental time-savings. This leap
      forward was made possible thanks to the employment of cryogenic helium as the gas
      to power magic angle sample spinning (MAS) for dynamic nuclear polarization (DNP)
      enhanced NMR experiments. These experimental conditions far exceed what is
      currently possible and allows currently reaching sample temperatures down to 30 K
      while conducting experiments with improved resolution (thanks to faster spinning
      frequencies, up to 25 kHz) and highly polarized nuclear spins. The impressive
      associated gains were used to hyperpolarize the surface of an industrial catalyst
      as well as to hyperpolarize organic nano-assemblies (self-assembling peptides in
      our case), for whom structures cannot be solved using diffraction techniques.
      Sustainable cryogenic helium sample spinning significantly enlarges the realm and
      possibilities of the MAS-DNP technique and is the route to transform NMR into a
      versatile but also sensitive atomic-level characterization tool.

PMID- 28757973
TI  - Pushing the limits of magnetic anisotropy in trigonal bipyramidal Ni(ii).
AB  - Monometallic complexes based on 3d transition metal ions in certain axial
      coordination environments can exhibit appreciably enhanced magnetic anisotropy,
      important for memory applications, due to stabilisation of an unquenched orbital
      moment. For high-spin trigonal bipyramidal Ni(ii), if competing structural
      distortions can be minimised, this may result in an axial anisotropy that is at
      least an order of magnitude stronger than found for orbitally non-degenerate
      octahedral complexes. Broadband, high-field EPR studies of [Ni(MDABCO)2Cl3]ClO4
      (1) confirm an unprecedented axial magnetic anisotropy, which pushes the limits
      of the familiar spin-only description. Crucially, compared to complexes with
      multidentate ligands that encapsulate the metal ion, we see only a very small
      degree of axial symmetry breaking. 1 displays field-induced slow magnetic
      relaxation, which is rare for monometallic Ni(ii) complexes due to efficient spin
      lattice and quantum tunnelling relaxation pathways.

PMID- 28757974
TI  - Overpotential for CO2 electroreduction lowered on strained penta-twinned Cu
      nanowires.
AB  - Based on first-principles calculations, we predict that penta-twinned Cu
      nanowires (NWs) are superior to conventional Cu catalysts for CO2
      electroreduction. The penta-twinned NWs possess a combination of ultrahigh
      mechanical strength, large surface-to-volume ratios and an abundance of
      undercoordinated adsorption sites, all desirable for CO2 electroreduction. In
      particular, we show that the penta-twinned Cu NWs can withstand elastic strains
      orders of magnitude higher than their conventional counterpart, and as a result
      their CO2 electroreduction activities can be significantly enhanced by elastic
      tensile strains. With a moderate tensile strain, the bias potential for methane
      production at a decent current density (2 mA cm-2) can be reduced by 50%. On the
      other hand, the competing hydrogen evolution reaction can be suppressed by the
      tensile strains. The presence of H at the NW surface is found to have a minor
      effect on CO2 electroreduction. Finally, we propose to use graphene as a
      substrate to stretch deposited Cu NWs.

PMID- 28757975
TI  - Conformationally restricted calpain inhibitors.
AB  - The cysteine protease calpain-I is linked to several diseases and is therefore a
      valuable target for inhibition. Selective inhibition of calpain-I has proved
      difficult as most compounds target the active site and inhibit a broad spectrum
      of cysteine proteases as well as other calpain isoforms. Selective inhibitors
      might not only be potential drugs but should act as tools to explore the
      physiological and pathophysiological roles of calpain-I. alpha-Mercaptoacrylic
      acid based calpain inhibitors are potent, cell permeable and selective inhibitors
      of calpain-I and calpain-II. These inhibitors target the calcium binding domain
      PEF(S) of calpain-I and -II. Here X-ray diffraction analysis of co-crystals of
      PEF(S) revealed that the disulfide form of an alpha-mercaptoacrylic acid bound
      within a hydrophobic groove that is also targeted by a calpastatin inhibitory
      region and made a greater number of favourable interactions with the protein than
      the reduced sulfhydryl form. Measurement of the inhibitory potency of the alpha
      mercaptoacrylic acids and X-ray crystallography revealed that the IC50 values
      decreased significantly on oxidation as a consequence of the stereo-electronic
      properties of disulfide bonds that restrict rotation around the S-S bond.
      Consequently, thioether analogues inhibited calpain-I with potencies similar to
      those of the free sulfhydryl forms of alpha-mercaptoacrylic acids.

PMID- 28757976
TI  - A carbon-carbon hybrid - immobilizing carbon nanodots onto carbon nanotubes.
AB  - The thrust of this work is to integrate small and uniformly sized carbon nanodots
      (CNDs) with single-walled carbon nanotubes (SWCNT) of different diameters as
      electron donors and electron acceptors, respectively, and to test their
      synergetic interactions in terms of optoelectronic devices. CNDs (denoted pCNDs,
      where p indicates pressure) were prepared by pressure-controlled microwave
      decomposition of citric acid and urea. pCNDs were immobilized on single-walled
      carbon nanotubes by wrapping the latter with poly(4-vinylbenzyl trimethylamine)
      (PVBTA), which features positively charged ammonium groups in the backbone.
      Negatively charged surface groups on the CNDs lead to attractive electrostatic
      interactions. Ground state interactions between the CNDs and SWCNTs were
      confirmed by a full-fledged photophysical investigation based on steady-state and
      time-resolved techniques. As a complement, charge injection into the SWCNTs upon
      photoexcitation was investigated by ultra-short time-resolved spectroscopy.

PMID- 28757977
TI  - Naphthalenebisimides as photofunctional surfactants for SWCNTs - towards water
      soluble electron donor-acceptor hybrids.
AB  - A water soluble naphthalenebisimide derivative (NBI) was synthesized and probed
      to individualize, suspend, and stabilize single wall carbon nanotubes (SWCNTs).
      Besides a comprehensive photophysical and electrochemical characterization of
      NBI, stable suspensions of SWCNTs were realized in buffered D2O. Overall, the
      dispersion efficiency of the NBI surfactant was determined by comparison with
      naphthalene based references. Successful individualization of SWCNTs was
      corroborated in several microscopic assays. In addition, emission spectroscopy
      points to the strong quenching of SWCNT centered band gap emission, when NBIs are
      immobilized onto SWCNTs. The origin of the quenching was found to be strong
      electronic communication, which leads to charge separation between NBIs and
      photoexcited SWCNTs, and, which yields reduced NBIs as well oxidized SWCNTs.
      Notably, electrochemical considerations revealed that the energy content of these
      charge separated states is one of the highest reported for SWCNT based electron
      donor-acceptor hybrids so far.

PMID- 28757978
TI  - The origin of the ligand-controlled regioselectivity in Rh-catalyzed [(2 + 2) +
      2] carbocyclizations: steric vs. stereoelectronic effects.
AB  - Density functional theory calculations demonstrate that the reversal of
      regiochemical outcome of the addition for substituted methyl propiolates in the
      rhodium-catalyzed [(2 + 2) + 2] carbocyclization with PPh3 and (S)-xyl-binap as
      ligands is both electronically and sterically controlled. For example, the ester
      functionality polarizes the alkyne pi* orbital to favor overlap of the methyl
      substituted terminus of the alkyne with the ppi-orbital of the alkenyl fragment
      of the rhodacycle during alkyne insertion with PPh3 as the ligand. In contrast,
      the sterically demanding xyl-binap ligand cannot accommodate the analogous alkyne
      orientation, thereby forcing insertion to occur at the sterically preferred ester
      terminus, overriding the electronically preferred orientation for alkyne
      insertion.

PMID- 28757979
TI  - Amorphous cobalt silicate nanobelts@carbon composites as a stable anode material
      for lithium ion batteries.
AB  - During the past decade, tremendous attention has been given to the development of
      new electrode materials with high capacity to meet the requirements of electrode
      materials with high energy density in lithium ion batteries. Very recently,
      cobalt silicate has been proposed as a new type of high capacity anode material
      for lithium ion batteries. However, the bulky cobalt silicate demonstrates
      limited electrochemical performance. Nanostructure engineering and carbon coating
      represent two promising strategies to improve the electrochemical performance of
      electrode materials. Herein, we developed a template method for the synthesis of
      amorphous cobalt silicate nanobelts which can be coated with carbon through the
      deposition and thermal decomposition of phenol formaldehyde resin. Tested as an
      anode material, the amorphous cobalt silicate nanobelts@carbon composites exhibit
      a reversible high capacity of 745 mA h g-1 at a current density of 100 mA g-1,
      and a long life span of up to 1000 cycles with a stable capacity retention of 480
      mA h g-1 at a current density of 500 mA g-1. The outstanding electrochemical
      performance of the composites indicates their high potential as an anode material
      for lithium ion batteries. The results here are expected to stimulate further
      research into transition metal silicate nanostructures for lithium ion battery
      applications.

PMID- 28757980
TI  - Pt/Ni(OH)2-NiOOH/Pd multi-walled hollow nanorod arrays as superior
      electrocatalysts for formic acid electrooxidation.
AB  - The catalytic activity and durability are crucial for the development of high
      performance electrocatalysts. To design electrocatalysts with excellent
      electroactivity and durability, the structure and composition are two important
      guiding principles. In this work, novel Pt/Ni(OH)2-NiOOH/Pd multi-walled hollow
      nanorod arrays (MHNRAs) are successfully synthesized. The unique MHNRAs provide
      fast transport and short diffusion paths for electroactive species and high
      utilization rate of catalysts. Because of the special surface and synergistic
      effects, the Pt/Ni(OH)2-NiOOH/Pd MHNRA electrocatalysts exhibit high catalytic
      activity, high durability and superior CO poisoning tolerance for the
      electrooxidation of formic acid in comparison with Pt@Pd MHNRAs, commercial Pt/C,
      Pd/C and PtRu/C catalysts.

PMID- 28757981
TI  - pi-extended [12]cycloparaphenylenes: from a hexaphenylbenzene cyclohexamer to its
      unexpected C2-symmetric congener.
AB  - The synthesis of pi-extended [12]cycloparaphenylene (CPP) derivatives from a
      kinked triangular macrocycle is presented. Depending on the reaction conditions
      for reductive aromatization, either a hexaphenylbenzene cyclohexamer or its C2
      symmetric congener was obtained. Their structures were confirmed by NMR
      spectroscopy or X-ray crystallographic analysis. With the support of DFT
      calculations, a mechanistic explanation for the unexpected formation of the oval
      shaped bis(cyclohexadiene)-bridged C2-symmetric macrocycle is provided. The here
      employed congested hexaphenylbenzene mode of connectivity in conjunction with a
      non-strained precursor improves oxidative cyclodehydrogenation toward the
      formation of ultrashort carbon nanotubes (CNT)s. Thus, this strategy can pave the
      way for new conceptual approaches of a solution-based bottom-up synthesis of
      CNTs.

PMID- 28757983
TI  - The approach to 4d/4f-polyphosphides.
AB  - The first 4d/4f polyphosphides were obtained by reaction of the divalent
      metallocenes [Cp*2Ln(thf)2] (Ln = Sm, Yb) with [{CpMo(CO)2}2(MU,eta2:2-P2)] or
      [Cp*Mo(CO)2(eta3-P3)]. Treatment of [Cp*2Ln(thf)2] (Ln = Sm, Yb) with
      [{CpMo(CO)2}2(MU,eta2:2-P2)] gave the 16-membered bicyclic compounds
      [(Cp2*Ln)2P2(CpMo(CO)2)4] (Ln = Sm, Yb) as the major products. From the reaction
      involving samarocene, the cyclic P4 complex [(Cp*2Sm)2P4(CpMo(CO)2)2] and the
      cyclic P5 complex [(Cp*2Sm)3P5(CpMo(CO)2)3] were also obtained as minor products.
      In each reaction, the P2 unit is reduced and a rearrangement occurred. In
      dedicated cases, a P-P bond formation takes place, which results in a new
      aggregation of the central phosphorus scaffold. In the reactions of
      [Cp*2Ln(thf)2] (Ln = Sm, Yb) with [Cp*Mo(CO)2P3] a new P-P bond is formed by
      reductive dimerization and the 4d/4f hexaphosphides [(Cp*2Ln)2P6(Cp*Mo(CO)2)2]
      (Ln = Sm, Yb) were obtained.

PMID- 28757982
TI  - Design, preparation, and selection of DNA-encoded dynamic libraries.
AB  - We report a method for the preparation and selection of DNA-encoded dynamic
      libraries (DEDLs). The library is composed of two sets of DNA-linked small
      molecules that are under dynamic exchange through DNA hybridization. Addition of
      the protein target shifted the equilibrium, favouring the assembly of high
      affinity bivalent binders. Notably, we introduced a novel locking mechanism to
      stop the dynamic exchange and "freeze" the equilibrium, thereby enabling
      downstream hit isolation and decoding by PCR amplification and DNA sequencing.
      Our DEDL approach has circumvented the limitation of library size and realized
      the analysis and selection of large dynamic libraries. In addition, this method
      also eliminates the requirement for modified and immobilized target proteins.

PMID- 28757984
TI  - A recyclable polyoxometalate-based supramolecular chemosensor for efficient
      detection of carbon dioxide.
AB  - A new type of supramolecular chemosensor based on the polyoxometalate (POM)
      Na9DyW10O36 (DyW10) and the block copolymer poly(ethylene oxide-b-N,N
      dimethylaminoethyl methacrylate) (PEO114-b-PDMAEMA16) is reported. By taking
      advantage of the CO2 sensitivity of PDMAEMA blocks to protonate the neutral
      tertiary amino groups, CO2 can induce the electrostatic coassembly of anionic
      DyW10 with protonated PDMAEMA blocks, and consequently trigger the luminescence
      chromism of DyW10 due to the change in the microenvironment of Dy3+. The hybrid
      complex in dilute aqueous solution is very sensitive to CO2 content and shows
      rapid responsiveness in luminescence. The luminescence intensity of the DyW10/PEO
      b-PDMAEMA complex increases linearly with an increasing amount of dissolved CO2,
      which permits the qualitative and quantitative detection of CO2. The complex
      solution also shows good selectivity for CO2, with good interference tolerance of
      CO, N2, HCl, H2O and SO2. The supramolecular chemosensor can be recycled through
      disassembly of the hybrid complex by simply purging with inert gases to remove
      CO2.

PMID- 28757985
TI  - Semiconductive 3-D haloplumbate framework hybrids with high color rendering index
      white-light emission.
AB  - Single-component white light materials may create great opportunities for novel
      conventional lighting applications and display systems; however, their reported
      color rendering index (CRI) values, one of the key parameters for lighting, are
      less than 90, which does not satisfy the demand of color-critical upmarket
      applications, such as photography, cinematography, and art galleries. In this
      work, two semiconductive chloroplumbate (chloride anion of lead(ii)) hybrids,
      obtained using a new inorganic-organic hybrid strategy, show unprecedented 3-D
      inorganic framework structures and white-light-emitting properties with high CRI
      values around 90, one of which shows the highest value to date.

PMID- 28757986
TI  - Discovery of low energy pathways to metal-mediated B
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      reduction guided by computation and experiment.
AB  - This manuscript describes a combination of DFT calculations and experiments to
      assess the reduction of borazines (B-N heterocycles) by eta6-coordination to
      Cr(CO)3 or [Mn(CO)3]+ fragments. The energy requirements for borazine reduction
      are established as well as the extent to which coordination of borazine to a
      transition metal influences hydride affinity, basicity, and subsequent reduction
      steps at the coordinated borazine molecule. Borazine binding to M(CO)3 fragments
      decreases the thermodynamic hydricity by >30 kcal mol-1, allowing it to easily
      accept a hydride. These hydricity criteria were used to guide the selection of
      appropriate reagents for borazine dearomatization. Reduction was achieved with an
      H2-derived hydride source, and importantly, a pathway which proceeds through a
      single electron reduction and H-atom transfer reaction, mediated by anthraquinone
      was uncovered. The latter transformation was also carried out electrochemically,
      at relatively positive potentials by comparison to all prior reports, thus
      establishing an important proof of concept for any future electrochemical BN bond
      reduction.

PMID- 28757987
TI  - Synthetic aminopyrrolic receptors have apoptosis inducing activity.
AB  - We report two synthetic aminopyrrolic compounds that induce apoptotic cell death.
      These compounds have been previously shown to act as receptors for mannosides.
      The extent of receptor-induced cell death is greater in cells expressing a high
      level of high-mannose oligosaccharides than in cells producing lower levels of
      high-mannose glycans. The ability of synthetic receptors to induce cell death is
      attenuated in the presence of external mannosides. The present results provide
      support for the suggestion that the observed cell death reflects an ability of
      the receptors to bind mannose displayed on the cell surface. Signaling pathway
      studies indicate that the synthetic receptors of the present study promote JNK
      activation, induce Bax translocation to the mitochondria, and cause cytochrome c
      release from the mitochondria into the cytosol, thus promoting caspase-dependent
      apoptosis. Such effects are also observed in cells treated with mannose-binding
      ConA. The present results thus serve to highlight what may be an attractive new
      approach to triggering apoptosis via modes of action that differ from those
      normally used to promote apoptosis.

PMID- 28757988
TI  - Multistep energy and electron transfer processes in novel rotaxane donor-acceptor
      hybrids generating microsecond-lived charge separated states.
AB  - A new set of [Cu(phen)2]+ based rotaxanes, featuring [60]-fullerene as an
      electron acceptor and a variety of electron donating moieties, namely zinc
      porphyrin (ZnP), zinc phthalocyanine (ZnPc) and ferrocene (Fc), has been
      synthesized and fully characterized with respect to electrochemical and
      photophysical properties. The assembly of the rotaxanes has been achieved using a
      slight variation of our previously reported synthetic strategy that combines the
      Cu(i)-catalyzed azide-alkyne cycloaddition reaction (the "click" or CuAAC
      reaction) with Sauvage's metal-template protocol. To underline our results,
      complementary model rotaxanes and catenanes have been prepared using the same
      strategy and their electrochemistry and photo-induced processes have been
      investigated. Insights into excited state interactions have been afforded from
      steady state and time resolved emission spectroscopy as well as transient
      absorption spectroscopy. It has been found that photo-excitation of the present
      rotaxanes triggers a cascade of multi-step energy and electron transfer events
      that ultimately leads to remarkably long-lived charge separated states featuring
      one-electron reduced C60 radical anion (C60-) and either one-electron oxidized
      porphyrin (ZnP+) or one-electron oxidized ferrocene (Fc+) with lifetimes up to 61
      microseconds. In addition, shorter-lived charge separated states involving one
      electron oxidized copper complexes ([Cu(phen)2]2+ (tau < 100 ns)), one-electron
      oxidized zinc phthalocyanine (ZnPc+; tau = 380-560 ns), or ZnP+ (tau = 2.3-8.4
      MUs), and C60- have been identified as intermediates during the sequence.
      Detailed energy diagrams illustrate the sequence and rate constants of the
      photophysical events occurring with the mechanically-linked chromophores. This
      work pioneers the exploration of mechanically-linked systems as platforms to
      position three distinct chromophores, which are able to absorb light over a very
      wide range of the visible region, triggering a cascade of short-range energy and
      electron transfer processes to afford long-lived charge separated states.

PMID- 28757989
TI  - CH3NH3PbI3 perovskite single crystals: surface photophysics and their interaction
      with the environment.
AB  - Here we identify structural inhomogeneity on a micrometer scale across the
      surface of a CH3NH3PbI3 perovskite single crystal. At the crystal edge a local
      distortion of the crystal lattice is responsible for a widening of the optical
      bandgap and faster photo-carrier recombination. These effects are inherently
      present at the edge of the crystal, and further enhanced upon water
      intercalation, as a preliminary step in the hydration of the perovskite material.

PMID- 28757990
TI  - Light and heat control over secondary structure and amyloid-like fiber formation
      in an overcrowded-alkene-modified Trp zipper.
AB  - The external photocontrol over peptide folding, by the incorporation of molecular
      photoswitches into their structure, provides a powerful tool to study biological
      processes. However, it is limited so far to switches that exhibit only a rather
      limited geometrical change upon photoisomerization and that show thermal
      instability of the photoisomer. Here we describe the use of an overcrowded alkene
      photoswitch to control a model beta-hairpin peptide. This photoresponsive unit
      undergoes a large conformational change and has two thermally stable isomers
      which has major influence on the secondary structure and the aggregation of the
      peptide, permitting the phototriggered formation of amyloid-like fibrils.

PMID- 28757991
TI  - AuICl-bound N-heterocyclic carbene ligands form MII4(LAuCl)6 integrally gilded
      cages.
AB  - The incorporation of an N-heterocyclic carbene (NHC) moiety into a self-assembled
      MII4L6 cage framework required the NHC first to be metallated with gold(i).
      Bimetallic cages could then be constructed using zinc(ii) and cadmium(ii)
      templates, showing weak luminescence. The cages were destroyed by the addition of
      further gold(i) in the form of AuI(2,4,6-trimethoxybenzonitrile)2SbF6, which
      caused the reversibly-formed cages to disassemble and controllably release the
      AuI-NHC subcomponent into solution. This release in turn induced the growth of
      gold nanoparticles. The rate of dianiline release could be tuned by capsule
      design or through the addition of chemical stimuli, with different release
      profiles giving rise to different nanoparticle morphologies.

PMID- 28757992
TI  - Emptying and filling a tunnel bronze.
AB  - The classical orthorhombic layered phase of V2O5 has long been regarded as the
      thermodynamic sink for binary vanadium oxides and has found great practical
      utility as a result of its open framework and easily accessible redox states.
      Herein, we exploit a cation-exchange mechanism to synthesize a new stable tunnel
      structured polymorph of V2O5 (zeta-V2O5) and demonstrate the subsequent ability
      of this framework to accommodate Li and Mg ions. The facile extraction and
      insertion of cations and stabilization of the novel tunnel framework is
      facilitated by the nanometer-sized dimensions of the materials, which leads to
      accommodation of strain without amorphization. The topotactic approach
      demonstrated here indicates not just novel intercalation chemistry accessible at
      nanoscale dimensions but also suggests a facile synthetic route to ternary
      vanadium oxide bronzes (M x V2O5) exhibiting intriguing physical properties that
      range from electronic phase transitions to charge ordering and superconductivity.

PMID- 28757993
TI  - Helically structured metal-organic frameworks fabricated by using supramolecular
      assemblies as templates.
AB  - The controlled formation of MOF-based superstructures with well-defined nanoscale
      sizes and exquisite morphologies represents a big challenge, but can trigger a
      new set of properties distinct from their bulk counterparts. Here we report on
      the use of a self-assembled organic object to template the first example of a
      nanoscale metal-organic framework (MOF) with a helical morphology. Two
      prototypical MOFs (HKUST-1 and MIL-100) were used to exemplify the growth of such
      materials on supramolecular assemblies. Interestingly, it was found that,
      dependent on the nature of the precursors, not only could well-defined helical
      MOF nanotubes be facilely fabricated, but novel helical bundle nanostructures
      could also be formed. These resultant MOF superstructures show additional optical
      properties and could be used as precursors for the preparation of chiral
      nanocarbons.

PMID- 28757994
TI  - van der Waals dispersion interactions in molecular materials: beyond pairwise
      additivity.
AB  - van der Waals (vdW) dispersion interactions are a key ingredient in the
      structure, stability, and response properties of many molecular materials and
      essential for us to be able to understand and design novel intricate molecular
      systems. Pairwise-additive models of vdW interactions are ubiquitous, but neglect
      their true quantum-mechanical many-body nature. In this perspective we focus on
      recent developments and applications of methods that can capture collective and
      many-body effects in vdW interactions. Highlighting a number of recent studies in
      this area, we demonstrate both the need for and usefulness of explicit many-body
      treatments for obtaining qualitative and quantitative accuracy for modelling
      molecular materials, with applications presented for small-molecule dimers,
      supramolecular host-guest complexes, and finally stability and polymorphism in
      molecular crystals.

PMID- 28757995
TI  - Vitrimers: permanent organic networks with glass-like fluidity.
AB  - Most covalent adaptable networks give highly interesting properties for material
      processing such as reshaping, recycling and repairing. Classical thermally
      reversible chemical cross-links allow for a heat-triggered switch between
      materials that behave as insoluble cured resins, and liquid thermoplastic
      materials, through a fully reversible sol-gel transition. In 2011, a new class of
      materials, coined vitrimers, was introduced, which extended the realm of
      adaptable organic polymer networks. Such materials have the remarkable property
      that they can be thermally processed in a liquid state without losing network
      integrity. This feature renders the materials processable like vitreous glass,
      not requiring precise temperature control. In this mini-review, an overview of
      the state-of-the-art in the quickly emerging field of vitrimer materials is
      presented. With a main focus on the chemical origins of their unique thermal
      behavior, the existing chemical systems and their properties will be discussed.
      Furthermore, future prospects and challenges in this important research field are
      highlighted.

PMID- 28757996
TI  - Going beyond electrospray: mass spectrometric studies of chemical reactions in
      and on liquids.
AB  - There has been a burst in the number and variety of available ionization
      techniques to use mass spectrometry to monitor chemical reactions in and on
      liquids. Chemists have gained the capability to access chemistry at unprecedented
      timescales, and monitor reactions and detect intermediates under almost any set
      of conditions. Herein, recently developed ionization techniques that facilitate
      mechanistic studies of chemical processes are reviewed. This is followed by a
      discussion of our perspective on the judicious application of these and similar
      techniques in order to study reaction mechanisms.

PMID- 28757997
TI  - Advanced 1,1-carboboration reactions with pentafluorophenylboranes.
AB  - The 1,1 carboboration reaction of a variety of metal-substituted alkynes with
      simple trialkylboranes R3B yields the respective alkenylboranes (Wrackmeyer
      reaction). The use of the strongly electrophilic R-B(C6F5)2 reagents allows for
      much milder reaction conditions and gives good yields of the respective bulky
      alkenylboranes from conventional terminal alkynes by means of 1,2-hydride
      migration. Even internal alkynes undergo 1,1-carboboration with the R-B(C6F5)2
      reagents, in this case yielding alkenylboranes by means of C-C bond cleavage.
      Phosphorus, sulfur or even boron containing substituents can serve as the
      migrating alkynyl substituents in the advanced 1,1-carboboration reactions using
      the R-B(C6F5)2 reagents. Sequential 1,1-carboboration of geminal bis(alkynyl)
      derivatives of these elements with the R-B(C6F5)2 boranes yields boryl
      substituted phospholes, thiophenes or even boroles in quite a variety. Vicinal
      bis(alkynyl)arenes or heteroarene substrates undergo benzannulation reactions in
      this way. Many of the -B(C6F5)2 substituted 1,1-carboboration products can be
      used as reagents in cross coupling reactions. A recently disclosed organometallic
      analogue, namely a 1,1-carbozirconation reaction is described.

PMID- 28757998
TI  - Electronic control of DNA-based nanoswitches and nanodevices.
AB  - Here we demonstrate that we can rationally and finely control the functionality
      of different DNA-based nanodevices and nanoswitches using electronic inputs. To
      demonstrate the versatility of our approach we have used here three different
      model DNA-based nanoswitches triggered by heavy metals and specific DNA sequences
      and a copper-responsive DNAzyme. To achieve electronic-induced control of these
      DNA-based nanodevices we have applied different voltage potentials at the surface
      of an electrode chip. The applied potential promotes an electron-transfer
      reaction that releases from the electrode surface a molecular input that
      ultimately triggers the DNA-based nanodevice. The use of electronic inputs as a
      way to finely activate DNA-based nanodevices appears particularly promising to
      expand the available toolbox in the field of DNA nanotechnology and to achieve a
      better hierarchical control of these platforms.

PMID- 28757999
TI  - Self-assembling alpha,gamma-cyclic peptides that generate cavities with tunable
      properties.
AB  - The design and synthesis of beta-sheet-based self-assembling cyclic peptides with
      tunable cavities is described. The incorporation of a gamma-amino acid with a
      hydroxyl group at C2 allows the incorporation of different groups that modify the
      internal properties of the resulting dimeric ensemble. These dimers can entrap
      different guests depending on the properties of the group at C2. The guest
      defines the geometry of the resulting aggregate.

PMID- 28758000
TI  - Persistent four-coordinate iron-centered radical stabilized by pi-donation.
AB  - Dinuclear iron carbonyl complex 2, which contains an elongated unsupported Fe-Fe
      bond, was synthesized by the reaction between Fe2(CO)9 and phosphinyl radical 1.
      Thermal Fe-Fe bond homolysis led to the generation of a four-coordinate carbonyl
      based iron-centered radical, 3, which is stabilized by pi-donation. Complex 3
      exhibited high reactivity toward organic radicals to form diamagnetic five
      coordinate Fe(ii) complexes.

PMID- 28758001
TI  - Seed-mediated growth of MOF-encapsulated Pd@Ag core-shell nanoparticles: toward
      advanced room temperature nanocatalysts.
AB  - The possibility of using inner cavities within metal-organic frameworks (MOFs) as
      templates for the fabrication of tiny metal nanoparticles (NPs) was attempted in
      this work. An unprecedented design of Pd@Ag core-shell NPs on MOFs via a seed
      mediated growth strategy is reported and attributed to the presence of activated
      physisorbed hydrogen atoms on embedded Pd NPs as reducing agents to selectively
      direct the deposition of Ag onto Pd while minimizing the Ag self-nucleation. The
      obtained Pd@Ag core-shell NPs exhibited a significant increase in selectivity in
      the partial hydrogenation of phenylacetylene as compared to their monometallic
      counterparts, due to the surface dilution and electron modification of the
      surface Pd sites by Ag deposition. Pd@Ag NPs also possessed an unprecedented high
      stability and recyclability in the catalytic reactions, related to the nano
      confinement effect and the strong metal-support interaction offered by the MOF
      framework.

PMID- 28758002
TI  - A minimalist fluorescent probe for differentiating Cys, Hcy and GSH in live
      cells.
AB  - A simple molecule, tetrafluoroterephthalonitrile (4F-2CN), was discovered to be
      an efficient fluorescent probe for detecting biological thiol species. The probe
      responded to Cys and emitted strong green fluorescence, whereas it reacted with
      Hcy/GSH and generated blue fluorescence. Addition of CTAB (cetyl
      trimethylammonium bromide) was observed to alter the fluorescence color of the
      reaction product of 4F-2CN and Hcy (from blue to green), but no alteration of the
      fluorescence color occurred for Cys and GSH. For the very first time, cell
      imaging experiments showed that the three commonly occurring thiols (Cys/Hcy/GSH)
      could be differentiated using a single fluorescent probe. In addition, the
      reaction product of 4F-2CN and Cys exhibits two-photon properties, offering a
      potentially useful tool for tissue imaging studies. To the best of our knowledge,
      4F-2CN is currently the smallest fluorescent probe for thiol detection. We
      envision that this new and versatile probe will be a useful tool for further
      elucidating the roles of thiols in biology.

PMID- 28758003
TI  - A local mode picture for H atom reaction with vibrationally excited H2O: a full
      dimensional state-to-state quantum dynamics investigation.
AB  - A local mode picture was postulated some time ago to explain the negligible OD
      product excitation from H reacting with D2O in fundamental asymmetrical
      excitation: the D2O asymmetric stretch state is best thought as a linear
      combination of local mode stretches with the H atom reacting preferentially with
      the excited OD bond, but has never been verified. Here we report the first full
      dimensional state-to-state study for the title reaction with H2O in the ground
      and the first symmetric and asymmetric stretching excited states. It is found
      that symmetric and asymmetric stretching excited states, which vibrate in very
      different ways in the normal mode picture, behave essentially identically in the
      reaction. More importantly, our calculations revealed that the reaction produces
      a small fraction of OH in the v = 1 state, with the population close to the
      relative reactivity between the ground and vibrationally excited states, and
      therefore it confirms the local mode picture for H2O in symmetric or asymmetric
      stretch states when reacting with an H atom.

PMID- 28758004
TI  - Precise, contactless measurements of the surface tension of picolitre aerosol
      droplets.
AB  - The surface composition and surface tension of aqueous droplets can influence key
      aerosol characteristics and processes including the critical supersaturation
      required for activation to form cloud droplets in the atmosphere. Despite its
      fundamental importance, surface tension measurements on droplets represent a
      considerable challenge owing to their small volumes. In this work, we utilize
      holographic optical tweezers to study the damped surface oscillations of a
      suspended droplet (<10 MUm radius) following the controlled coalescence of a pair
      of droplets and report the first contactless measurements of the surface tension
      and viscosity of droplets containing only 1-4 pL of material. An advantage of
      performing the measurement in aerosol is that supersaturated solute states
      (common in atmospheric aerosol) may be accessed. For pairs of droplets starting
      at their equilibrium surface composition, surface tensions and viscosities are
      consistent with bulk equilibrium values, indicating that droplet surfaces respond
      to changes in surface area on microsecond timescales and suggesting that
      equilibrium values can be assumed for growing atmospheric droplets. Furthermore,
      droplet surfaces are shown to be rapidly modified by trace species thereby
      altering their surface tension. This equilibration of droplet surface tension to
      the local environmental conditions is illustrated for unknown contaminants in
      laboratory air and also for droplets exposed to gas passing through a water
      ethanol solution. This approach enables precise measurements of surface tension
      and viscosity over long time periods, properties that currently are poorly
      constrained.

PMID- 28758005
TI  - Protein sensing in living cells by molecular rotor-based fluorescence-switchable
      chemical probes.
AB  - In this paper, we introduce a general design to construct fluorescence-switching
      probes by using conjugates of a fluorescent molecular rotor and protein specific
      ligands for the selective protein detection and real-time tracking of protein
      degradation in living cells. Upon the interaction of the ligand with the protein
      ligand-binding domain, the crowded surroundings restrict the bond rotation of the
      fluorescent molecular rotor to trigger the emission of a strong fluorescence
      signal, which is reduced upon the addition of a competitive ligand or after
      protein degradation. With this probe design, two fluorescent probes for MGMT and
      hCAII proteins were constructed and applied for detecting the endogenous proteins
      in living cells. In addition, real-time degradation kinetics of the alkylated
      MGMT at the single living cell level were revealed for the first time. We believe
      that this fluorescence-switching probe design can possibly be extended for the
      analysis of other proteins, for which there are still no effective tools to
      visualize them in living cells.

PMID- 28758006
TI  - Enantioselective gamma-borylation of unsaturated amides and stereoretentive
      Suzuki-Miyaura cross-coupling.
AB  - The rhodium-catalyzed, directed catalytic asymmetric hydroboration of gamma,delta
      unsaturated amides affords a direct route to chiral acyclic secondary gamma
      borylated carbonyl derivatives in high enantiomeric purity. In contrast to a
      similar beta-borylated amide derivative, the gamma-borylated amide undergoes
      Suzuki-Miyaura cross-coupling with stereoretention. The utility of the boronic
      ester products is further illustrated by other stereospecific C-B bond
      transformations leading to gamma-amino acid derivatives, 1,4-amino alcohols, and
      5-substituted-gamma-lactone and gamma-lactam ring systems.

PMID- 28758007
TI  - Re-epithelialization of whole porcine kidneys with renal epithelial cells.
AB  - Decellularized porcine kidneys were recellularized with renal epithelial cells by
      three methods: perfusion through the vasculature under high pressure, perfusion
      through the ureter under high pressure, or perfusion through the ureter under
      moderate vacuum. Histology, scanning electron microscopy, confocal microscopy,
      and magnetic resonance imaging were used to assess vasculature preservation and
      the distribution of cells throughout the kidneys. Cells were detected in the
      magnetic resonance imaging by labeling them with iron oxide. Perfusion of cells
      through the ureter under moderate vacuum (40 mmHg) produced the most uniform
      distribution of cells throughout the kidneys.

PMID- 28758008
TI  - Bilateral extramedullary adrenal plasmacytoma: case report and review of the
      literature.
AB  - Extramedullary plasmacytoma (EMP) accounts for only 3% of plasma cell
      malignancies; others include multiple myeloma, plasma cell leukemia and solitary
      plasmacytoma of bone. The majority of EMPs are found in the upper respiratory
      tract. Other sites include the GI tract, bladder, CNS, thyroid, breast, testes,
      parotid gland, lymph nodes and skin. There are eight cases in the literature of
      adrenal plasmacytoma, however, only two were bilateral. We describe our recent
      experience of bilateral adrenal plasmacytoma and review of the literature. While
      EMP may present as aggressive locally destructive lesions, excellent local
      control can be achieved in a majority of cases. Follow-up should be lifelong due
      to risk of progression to multiple myeloma.

PMID- 28758009
TI  - 11-Deoxycortisol may be superior to cortisol in confirming a successful adrenal
      vein catheterization without cosyntropin: a pilot study.
AB  - AIM: We aimed to compare the performance of nine adrenal steroids in confirming
      the correct catheter position during adrenal venous sampling (AVS) without
      cosyntropin in patients with primary hyperaldosteronism. MATERIALS & METHODS: A
      successful adrenal vein catheterization without cosyntropin was defined as the
      ratio of steroids from adrenal to peripheral veins being >3:1. AVS samples from
      four patients with primary hyperaldosteronism were analyzed. RESULTS: Compared
      with the mean ratio of cortisol without cosyntropin, the ratios of 11
      deoxycortisol (p = 0.008), dehydroepiandrosterone (p = 0.01) and androstenedione
      (p = 0.008) were significantly higher. None of the ratios (n = 8) of cortisol
      from adrenal to peripheral veins exceeded 3:1, while all ratios of 11
      deoxycortisol (p < 0.001) were >3. CONCLUSION: Cosyntropin infusion during AVS
      may not be necessary if 11-deoxycortisol is used to confirm catheter position.

PMID- 28751963
TI  - L-arginine supplementation and risk factors of cardiovascular diseases in healthy
      men: a double-blind randomized clinical trial.
AB  - Context: The effect of L-arginine on risk factors of cardiovascular diseases
      (CVD) has mostly focused on western countries. Since cardiovascular diseases is
      the second cause of death in Iran and, as far as we are aware, there have been no
      studies about the effect of L-arginine on CVD risk factors, the aim of this trial
      was to assess the effects of L-arginine supplementation on CVD risk factors in
      healthy men. Objective: The purpose of this study was to evaluate the effect of
      low-dose L-arginine supplementation on CVD risk factors (lipid profile, blood
      sugar and blood pressure) in Iranian healthy men. Design, setting, participants:
      We conducted a double-blind randomized controlled trial in 56 patients selected
      from sport clubs at the Isfahan University of Medical Science between November
      2013 and December 2013. Interventions: Healthy men received L-arginine
      supplementation (2000 mg daily) in the intervention group or placebo (2000 mg
      maltodextrin daily) in the control group for 45 days. Main outcome measure: The
      primary outcome measures were we measured the levels of fasting blood sugar,
      blood pressure and lipid profile including triglyceride (TG), cholesterol, LDL
      and HDL in healthy subjects. It was hypothesized that these measures would be
      significantly improved in those receiving L-arginine supplementation. at the
      beginning and end of the study. Results: In this trial, we had complete data for
      52 healthy participants with mean age of 20.85+/-4.29 years. At the end of study,
      fasting blood sugar (P=0.001) and lipid profile (triglycerideTG (P<0.001),
      cholesterol (P<0.001), LDL (P=0.04), HDL (P=0.015)) decreased in the L-arginine
      group but we found no significant change in the placebo group. In addition, the
      reduction of fasting blood sugar and lipid profile in L-arginine was significant
      compared with placebo group. No significant changes were found about systolic
      (P=0.81) and diastolic blood pressure either in L-arginine or placebo group.
      (P=0.532). Conclusion: The use of L-arginine significantly improved outcomes
      compared to placebo.

PMID- 28751964
TI  - Method-centered digital communities on protocols.io for fast-paced scientific
      innovation.
AB  - The Internet has enabled online social interaction for scientists beyond physical
      meetings and conferences. Yet despite these innovations in communication,
      dissemination of methods is often relegated to just academic publishing. Further,
      these methods remain static, with subsequent advances published elsewhere and
      unlinked. For communities undergoing fast-paced innovation, researchers need new
      capabilities to share, obtain feedback, and publish methods at the forefront of
      scientific development. For example, a renaissance in virology is now underway
      given the new metagenomic methods to sequence viral DNA directly from an
      environment. Metagenomics makes it possible to "see" natural viral communities
      that could not be previously studied through culturing methods. Yet, the
      knowledge of specialized techniques for the production and analysis of viral
      metagenomes remains in a subset of labs.  This problem is common to any community
      using and developing emerging technologies and techniques. We developed new
      capabilities to create virtual communities in protocols.io, an open access
      platform, for disseminating protocols and knowledge at the forefront of
      scientific development. To demonstrate these capabilities, we present a virology
      community forum called VERVENet. These new features allow virology researchers to
      share protocols and their annotations and optimizations, connect with the broader
      virtual community to share knowledge, job postings, conference announcements
      through a common online forum, and discover the current literature through
      personalized recommendations to promote discussion of cutting edge research.
      Virtual communities in protocols.io enhance a researcher's ability to: discuss
      and share protocols, connect with fellow community members, and learn about new
      and innovative research in the field.  The web-based software for developing
      virtual communities is free to use on protocols.io. Data are available through
      public APIs at protocols.io.

PMID- 28751967
TI  - Protein sites with more coevolutionary connections tend to evolve slower, while
      more variable protein families acquire higher coevolutionary connections.
AB  - Background: Amino acid exchanges within proteins sometimes compensate for one
      another and could therefore be co-evolved. It is essential to investigate the
      intricate relationship between the extent of coevolution and the evolutionary
      variability exerted at individual protein sites, as well as the whole protein.
      Methods: In this study, we have used a reliable set of coevolutionary connections
      (sites within 10A spatial distance) and investigated their correlation with the
      evolutionary diversity within the respective protein sites. Results: Based on our
      observations, we propose an interesting hypothesis that higher numbers of
      coevolutionary connections are associated with lesser evolutionary variable
      protein sites, while higher numbers of the coevolutionary connections can be
      observed for a protein family that has higher evolutionary variability. Our
      findings also indicate that highly coevolved sites located in a solvent
      accessible state tend to be less evolutionary variable. This relationship reverts
      at the whole protein level where cytoplasmic and extracellular proteins show
      moderately higher anti-correlation between the number of coevolutionary
      connections and the average evolutionary conservation of the whole protein.
      Conclusions: Observations and hypothesis presented in this study provide
      intriguing insights towards understanding the critical relationship between
      coevolutionary and evolutionary changes observed within proteins. Our
      observations encourage further investigation to find out the reasons behind
      subtle variations in the relationship between coevolutionary connectivity and
      evolutionary diversity for proteins located at various cellular localizations
      and/or involved in different molecular-biological functions.

PMID- 28751968
TI  - Lumboperitoneal shunt insertion without fluoroscopy guidance: Accuracy of
      placement in a series of 107 procedures.
AB  - Background: Lumboperitoneal (LP) shunts were the mainstay of cerebrospinal fluid
      diversion therapy for idiopathic intracranial hypertension (IIH). The
      traditionally cited advantage of LP shunts over ventriculoperitoneal (VP) shunts
      is the ease of insertion in IIH. This needs to be placed at the level of L3/4 to
      be below the level of the spinal cord. The objective of this study was to analyse
      the position of LP shunts inserted without portable fluoroscopy guidance. 
      Methods: A retrospective analysis of radiology was performed for patients who
      underwent lumboperitoneal shunts between 2006 and 2016 at the National Hospital
      for Neurology and Neurosurgery. Patients who had insertion of a LP shunt without
      fluoroscopy guidance were selected.  Patients without post-procedural imaging
      were excluded. A retrospective analysis of the clinical notes was also performed.
      Results: Between 2006 and 2016, 163 lumboperitoneal shunts were inserted in 105
      patients. A total of 56 cases were excluded due to lack of post-procedural
      imaging; therefore, 107 post-procedural x-rays were reviewed. In 17 (15.8%) cases
      the proximal end of the LP shunt was placed at L1/L2 level or above. 
      Conclusions: Insertion of LP shunts without portable fluoroscopy guidance gives a
      15.8% risk of incorrect positioning of the proximal end of the catheter. We
      suggest that x-ray is recommended to avoid incorrect level placement. Further
      investigation could be carried out with a control group with fluoroscopy against
      patients without.

PMID- 28758010
TI  - Skin cancer screening: recommendations for data-driven screening guidelines and a
      review of the US Preventive Services Task Force controversy.
AB  - Melanoma is usually apparent on the skin and readily detected by trained medical
      providers using a routine total body skin examination, yet this malignancy is
      responsible for the majority of skin cancer-related deaths. Currently, there is
      no national consensus on skin cancer screening in the USA, but dermatologists and
      primary care providers are routinely confronted with making the decision about
      when to recommend total body skin examinations and at what interval. The
      objectives of this paper are: to propose rational, risk-based, data-driven
      guidelines commensurate with the US Preventive Services Task Force screening
      guidelines for other disorders; to compare our proposed guidelines to
      recommendations made by other national and international organizations; and to
      review the US Preventive Services Task Force's 2016 Draft Recommendation
      Statement on skin cancer screening.

PMID- 28758015
TI  - Applying generalized additive models to unravel dynamic changes in anthocyanin
      biosynthesis in methyl jasmonate elicited grapevine (Vitis vinifera cv. Gamay)
      cell cultures.
AB  - Plant cell cultures represent important model systems to understand metabolism
      and its modulation by regulatory factors. Even in controlled conditions, cell
      metabolism is highly dynamic and can be fully characterized only by time course
      experiments. Here, we show that statistical analysis of this type of data gains
      power if it moves to approaches able to compare the 'trends' of the different
      metabolites. In particular, we show how generalized additive models can be used
      to model the time-dependent profile of anthocyanin synthesis in grapevine cell
      suspension cultures (Vitis vinifera cv. Gamay), following treatment with 100 MUm
      methyl jasmonate. The sampling was performed daily for 20 days of culturing
      following elicitation at day 5. All samples were analyzed by UPLC-MS/MS for the
      identification and quantification of fifteen anthocyanin compounds. The models
      confirmed the separation in the anthocyanin biosynthetic pathway between
      delphinidin-based and cyanidin-based compounds, showing that methyl jasmonate
      modulates the anthocyanin concentration profiles. Our results clearly indicate
      that the combination of high-throughput metabolomics and state of the art
      statistical modeling is a powerful approach to study plant metabolism. This
      approach is expected to gain popularity due to the growing availability of low
      cost high-throughput 'omic' assays.

PMID- 28758016
TI  - Norgestimate inhibits staphylococcal biofilm formation and resensitizes
      methicillin-resistant Staphylococcus aureus to beta-lactam antibiotics.
AB  - Formation of bacterial biofilms on medical devices can cause severe or fatal
      infectious diseases. In particular, biofilm-associated infections caused by
      methicillin-resistant Staphylococcus aureus are difficult to eradicate because
      the biofilm is strongly resistant to antibiotics and the host immune response.
      There is no effective treatment for biofilm-associated infectionss, except for
      surgical removal of contaminated medical devices followed by antibiotic therapy.
      Here we show that norgestimate, an acetylated progestin, effectively inhibits
      biofilm formation by staphylococcal strains, including methicillin-resistant S.
      aureus, without inhibiting their growth, decreasing the selective pressure for
      emergence of resistance. 17-Deacetyl norgestimate, a metabolite of norgestimate,
      shows much weaker inhibitory activity against staphylococcal biofilm formation,
      indicating that the acetyl group of norgestimate is important for its activity.
      Norgestimate inhibits staphylococcal biofilm formation by inhibiting production
      of polysaccharide intercellular adhesin and proteins in the extracellular matrix.
      Proteome analysis of S. aureus indicated that norgestimate represses the
      expression of the cell wall-anchored protein SasG, which promotes intercellular
      adhesion, and of the glycolytic enzyme enolase, which plays a secondary role in
      biofilm formation. Notably, norgestimate induces remarkable changes in cell wall
      morphology, characterized by increased thickness and abnormal rippled septa.
      Furthermore, norgestimate increases the expression level of penicillin binding
      protein 2 and resensitizes methicillin-resistant S. aureus to beta-lactam
      antibiotics. These results suggest that norgestimate is a promising lead compound
      for the development of drugs to treat biofilm-associated infections, as well as
      for its ability to resensitize methicillin-resistant S. aureus to beta-lactam
      antibiotics.

PMID- 28758017
TI  - Towards an ideal antiretroviral regimen for the global HIV epidemic.
AB  - Currently, immediate initiation of antiretroviral therapy (ART) is recommended
      for all individuals with HIV infection. However, among the 37 million people
      estimated to be living with HIV/AIDS, only 17 million are actively on treatment.
      Optimal use of ART among HIV-infected and at-risk individuals reduces morbidity,
      mortality, transmission and acquisition of HIV infection. ART regimen choices are
      affected by factors such as economic differences between resource-rich and low-
      and middle-income countries (LIMC), drug availability, and considerations for use
      in special populations. Ideal ART regimens combine high efficacy, high
      tolerability, low toxicity, low pill burden, affordability and global
      availability. Here, we highlight five aspects to be considered when thinking of
      an ideal global ART regimen: (1) the co-administration with other medications
      especially tuberculosis treatment; (2) treatment for specific populations such as
      women, children, adolescents, older people and acutely infected individuals; (3)
      efficacy; (4) safety, tolerability and convenience; and (5) affordability and
      global access for all PLWH.

PMID- 28758018
TI  - The road to elimination of hepatitis C: analysis of cures versus new infections
      in 91 countries.
AB  - BACKGROUND: Hepatitis C (HCV) can only be eradicated if annual rates of cure
      (SVR) are consistently and significantly higher than new HCV infections, across
      many countries. In 2016, the WHO called for a 90% reduction in new HCV infection
      by 2030. Direct-acting antivirals (DAA) can cure the majority of those treated,
      at around 90% in most populations, at potentially very low prices. We compared
      the net annual change in epidemic size across 91 countries using data on SVR, new
      HCV infections, and deaths. In a further 109 countries, we projected this figure
      using regional averages of epidemic size. METHODS: Epidemiological data for 2016
      were extracted from national reports, publications and the Polaris Observatory.
      There were 91/210 countries with data on SVR, HCV-related deaths and new
      infections available for analysis; 109 countries had net change in epidemic size
      projected from the regional prevalence of HCV, extrapolated to their population
      size. 'Net cure' was defined as the number of people with SVR, minus new HCV
      infections, plus HCV-related deaths in 2016. RESULTS: For the 91 countries
      analysed, there were 57.3 million people with chronic HCV infection in 2016. In
      the remaining 109 countries, the projected epidemic size was 12.2 million, giving
      a global epidemic size of 69.6 million. Across the 91 countries, there was a fall
      from 57.3 to 56.9 million people in 2017, a 0.7% reduction. The projected global
      net change was from 69.6 to 69.3 million, a 0.4% reduction. Ten countries had at
      least five times more people reaching SVR than new HCV infections, including
      Egypt and USA. In 47/91 countries, there were more HCV infections than SVR in
      2016. CONCLUSION: Very few countries are on target to achieve elimination of HCV
      as a public health problem by 2030. While the North American, North
      African/Middle East and Western European regions have shown small declines in
      prevalence, the epidemic is growing in sub-Saharan Africa and Eastern Europe. Far
      higher rates of DAA treatment are required for worldwide elimination of HCV.

PMID- 28758019
TI  - Current trends in Zika vaccine development.
AB  - The Zika virus (ZIKV) was first isolated in 1947 in Uganda. While it took 60
      years for this virus to cause major outbreaks, an important shift in its ability
      to cause epidemics took place in the first and second decades of the this
      century: in 2007 in Yap Island, Micronesia, followed by French Polynesia in 2013
      and, finally in 2015 and 2016, when ZIKV infections occurred throughout South
      America, Central America and the Caribbean, spreading rapidly to reach North
      America in just a single year. No licensed prophylactic vaccine is yet available
      but recent efforts towards the development of a vaccine have been remarkable from
      both the private and public sectors and include new candidate vaccines ranging
      from the classical live-attenuated or inactivated vaccines to more sophisticated
      approaches such as mRNA or genetically engineered viral platforms. Previous
      successes with licensed flavivirus vaccines indicate that a protective ZIKV
      vaccine should be an achievable goal. Nevertheless, numerous pre- and post
      licensure challenges need to be taken into account, such as the interaction of
      vaccine-induced immune responses with other flaviviruses, in particular with
      dengue, where antibody-dependent enhancement could become an issue, and the
      importance of a rapid induction of protective responses during pregnancy.

PMID- 28758020
TI  - Factors associated with intention to take non-occupational HIV post-exposure
      prophylaxis among Thai men who have sex with men.
AB  - BACKGROUND: Men who have sex with men (MSM) are disproportionately infected with
      HIV in Thailand. Factors affecting their intention to take non-occupational HIV
      post-exposure prophylaxis (nPEP) are not well understood. This study sought to
      determine factors associated with an intention to take nPEP in this population.
      METHOD: This is a two-phase mixed-method study. Phase I was a cross-sectional
      survey of intention to take nPEP in 450 MSM attending for HIV testing, using a
      self-administered questionnaire. Phase II was a prospective descriptive study,
      using an in-depth interview among 40 MSM who had been exposed to HIV in the past
      72 hours. Multiple logistic regression was used to evaluate factors relating to
      the intention to use nPEP. RESULTS: Among 450 MSM seeking HIV testing in Bangkok,
      7% had ever taken nPEP. Only 40% expressed an intention to take it to prevent HIV
      acquisition, despite the fact that they were at high risk as evidenced by an
      18.9% prevalence of HIV-positive status. Factors associated with an intention to
      take nPEP were awareness about nPEP, HIV knowledge, mode of sexual intercourse
      and circumcision. Among 40 MSM who were eligible for and offered nPEP, 39 agreed
      to take it, and all but one completed the 4-week course. Condom use increased and
      all 32 individuals who could be contacted tested HIV negative after nPEP.
      CONCLUSION: A high HIV prevalence was found in MSM testing for HIV in this study.
      However, fewer than half of the participants expressed the intention to take nPEP
      if they were at risk for HIV infection. Efforts to create nPEP awareness and
      improve HIV knowledge in MSM are crucial to the successful implementation of nPEP
      as part of a combination package for HIV prevention in this high-risk population.

PMID- 28758021
TI  - HIV disclosure and stigma among women living with HIV in Denmark.
AB  - OBJECTIVE: To identify disclosure, stigma and predictors of non-disclosure among
      women living with HIV in Denmark. METHODS: A questionnaire study of women living
      with HIV in Denmark was performed. The enrolment period was from February 2013 to
      March 2014. Logistic regression was used to estimate predictors of non
      disclosure. RESULTS: A total of 234 participants were included. The majority
      (94%) had disclosed their HIV status to at least one person outside their
      healthcare environment, although 29% had disclosed to fewer than three people.
      Confidantes were mostly partners (96%), siblings (63%), friends (63%) and
      children (41%). The primary reason for non-disclosure was a feeling that it did
      not concern others (55%), although reactions upon disclosure were mainly positive
      in 53%. Predictors of non-disclosure were being of black or Asian ethnicity.
      Following their HIV diagnosis, 40% no longer dared to have sex, 40% felt isolated
      and 23% felt that others were afraid and kept a physical distance. In contrast,
      after disclosure 75% felt better at taking decisions about life and 50% were in
      closer contact with family and friends. CONCLUSION: Almost one-third of
      participants disclosed their HIV diagnosis to fewer than three people and black
      or Asian ethnicity predicted non-disclosure. HIV-related stigma regarding sex and
      contact with others is still highly prevalent; however, reactions to disclosure
      were mainly positive and associated with secondary positive gains. We strongly
      urge healthcare professionals to initiate a dialogue regarding stigma and
      disclosure with women living with HIV with a view to increasing disclosure and
      minimising stigmatisation in this vulnerable population.

PMID- 28758022
TI  - Factors associated with early menopause among women in Nigeria.
AB  - OBJECTIVES: Effective antiretroviral therapy has prolonged the survival of
      patients with HIV. Accordingly, studies of the consequences of ageing are
      increasingly important. We determined the prevalence of early menopause (EM) and
      its associated factors in a cohort of HIV-infected and HIV-negative controls in
      Jos, Nigeria. METHODS: HIV-infected women accessing care in an ambulatory setting
      and their negative counterparts from the general population were included.
      Menopause was defined as having gone one year since the last menstrual period. EM
      was defined as the onset of menopause at <=45 years of age. Baseline
      characteristics were compared and logistic regression analyses were used to
      determine factors independently associated with EM. RESULTS: Out of a total of
      253 women included, 58 attained menopause early, giving an EM prevalence of 22.9%
      (95% confidence interval [CI] 17.9-28.6%). Women with EM were younger (P<0.001)
      and had been infected with HIV for a shorter period (P=0.007). Baseline CD4+ cell
      count (P=0.66) and viral load (P=0.15) were similar among those with and without
      EM. For all subjects, HIV infection (adjusted odds ratio [AOR}=10.95, 95% CI 1.39
      86.33) and sexual activity (AOR=2.37, 95% CI 1.24-4.52) were associated with EM
      while early menarche (AOR=14.88, 95% CI 1.37-161.10) and sexual activity
      (AOR=2.02, 95% CI 1.03-3.96) were independently associated with EM. CONCLUSION:
      Over a quarter of our postmenopausal women attained menopause early. No HIV
      related factor predicted EM in this study. A better understanding of ageing in
      these women is important to determine a more appropriate disease-management
      approach during this period of life.

PMID- 28758023
TI  - Strategies to improve the uptake of effective contraception in perinatally HIV
      infected adolescents.
AB  - OBJECTIVE: To assess strategies to improve safe-sex practices in sexually active
      female adolescents living with HIV, through linking reproductive health (RH) care
      with HIV care. METHODS: A single arm, 48-week prospective study was conducted
      with 77 sexually active adolescents in five sites in Thailand. Guided RH
      education was carried out through video, brochures and individual counselling.
      Participants were offered free effective contraception (EC), in addition to a
      barrier method (dual contraception) versus barrier method only. Changes in EC use
      were assessed with McNemar's test; predicting factors with logistic regression.
      RESULTS: Median age was 19 years; 95% were perinatally infected; 30% had been
      pregnant. All but one showed RH-knowledge improvement after RH education.
      Individual counselling was most often rated the 'most helpful' educational
      method. At the screening visit 21% were using dual contraception; 53% a male
      condom only; 8% EC method only; and 18% were not using any contraceptive method.
      Dual-contraception use improved with time, reaching 74% at week 48. EC-use at the
      baseline visit was associated with having ever used EC prior to study entry
      (P<0.0001), and the study site (P<0.0001). Having ever used EC was associated
      with a history of pregnancy (P=0.0085) and forced sex (P=0.0386). CONCLUSION:
      Offering continuous RH care, linked with HIV care, resulted in increased use of
      dual contraception. Healthcare providers played a significant role in the
      process. RH education should address the main predictors for EC use by
      adolescents, including past, personal experience.

PMID- 28758024
TI  - Serum lipid and glucose profiles in HIV-positive Nigerian children.
AB  - OBJECTIVES: To describe the fasting serum lipid and glucose profiles of HIV
      positive Nigerian children and determine the prevalence and risk factors for
      dyslipidaemia and hyperglycaemia, which are risk factors for cardiovascular
      diseases. METHODS: This was a comparative cross-sectional study carried out at
      the Paediatric Infectious Disease Clinic (PIDC) of the Jos University Teaching
      Hospital (JUTH) for HIV-positive children and at two primary schools in Jos for
      HIV-negative children as controls. One hundred and forty-two HIV-positive
      children aged 6-18 years and an equal number of controls were studied by
      determining their fasting serum lipid and glucose levels. The prevalence of
      dyslipidaemia and hyperglycaemia was determined and their risk factors obtained
      using multivariate logistic regression. P values of less than 0.05 were
      considered statistically significant. RESULTS: Mean triglyceride levels were
      significantly higher in HIV-positive children compared with controls at 87.2
      mg/dL (95% confidence interval [CI] 79.4-95.0) and 68.1 mg/dL (95% CI 62.5-72.7),
      respectively (P<0.001). There were no significant differences in mean glucose
      levels. Dyslipidaemia was significantly higher in HIV-positive children (21.8%)
      compared with controls (12.7%; P=0.04). Total serum cholesterol was elevated in
      17 (12.0%) HIV-positive participants compared with seven (4.9%) of controls
      (P=0.02). Children on lopinavir/ritonavir (LPV/r) and those with no significant
      or mild disease had a significantly higher prevalence of hypercholesterolaemia
      (33.3% vs 4.8% and 14.5% vs 0.0%, respectively; P<0.001). CONCLUSION: HIV
      positive children on antiretroviral (ARV) drugs, especially LPV/r, should have
      their lipids regularly monitored as those with dyslipidaemia stand the risk of
      subsequently developing cardiovascular diseases.

PMID- 28758025
TI  - Pursuing ethical coherence in the prevention of vertical transmission of HIV:
      justice and injustice in Option B.
AB  - Improved prevention of vertical transmission of HIV is an essential part of the
      global response to HIV. The Option B+ strategy took the extraordinary step of
      treating many non-pregnant women living with HIV (those with CD4 cell counts >350
      cells/mm3) in the absence of evidence that they themselves would benefit from
      ART. This example of so-called AIDS exceptionalism reflects an understanding that
      the global response to HIV demands a different set of morals. This philosophical
      article explores a retrospective analysis of the ethical arguments made in
      support of Option B+ incorporating utilitarian, feminist and equity-based
      frameworks. A number of inconsistencies were found in the arguments made for the
      introduction of Option B+ well before results were available from the START and
      TEMPRANO trials. Although some people think 'the ends justify the means', we
      conclude that erroneous justifications were initially given in support of Option
      B+. We identify tensions that remain in light of these results and argue that
      future strategies would benefit from a community-focused, human rights-based
      approach.

PMID- 28758026
TI  - Scaling up HIV self-testing in China and Africa.

PMID- 28758027
TI  - Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine HIV pre
      exposure prophylaxis: clinical guidelines.
AB  - Daily use of coformulated tenofovir and emtricitabine for HIV pre-exposure
      prophylaxis (PrEP) by populations at high risk of HIV infection is now
      recommended in guidelines from the United States, Europe and Australia and
      globally through the 2015 WHO guidelines. These 2017 Australasian Society for
      HIV, Viral Hepatitis and Sexual Health Medicine's (ASHM) PrEP Guidelines are an
      updated adaptation of the 2014 US Centers for Disease Control's PrEP guidelines
      and are designed to: *Support the prescription of PrEP using forms of
      coformulated tenofovir and emtricitabine that have been registered in Australia
      by the Therapeutic Goods Administration and other bioequivalent generic drugs
      that are available in Australia through self-importation, private prescription or
      Australian PrEP clinical trials*Assist clinicians in the evaluation of patients
      who are seeking PrEP*Assist clinicians in commencing and monitoring patients on
      PrEP including PrEP dosing schedules, management of side-effects and toxicity,
      use of PrEP in pregnancy and in chronic hepatitis B infection and how to cease
      PrEP Daily PrEP with co-formulated tenofovir and emtricitabine, used continuously
      or for shorter periods of time, is recommended in these guidelines as a key HIV
      prevention option for men who have sex with men (MSM), transgender men and women,
      heterosexual men and women, and people who inject drugs (PWID) at substantial
      risk of HIV acquisition.

PMID- 28758029
TI  - Concern noted: A descriptive study of editorial expressions of concern in PubMed
      and PubMed Central.
AB  - BACKGROUND: An editorial expression of concern (EEoC) is issued by editors or
      publishers to draw attention to potential problems in a publication, without
      itself constituting a retraction or correction. METHODS: We searched PubMed,
      PubMed Central (PMC), and Google Scholar to identify EEoCs issued for
      publications in PubMed and PMC up to 22 August 2016. We also searched the
      archives of the Retraction Watch blog, some journal and publisher websites, and
      studies of EEoCs. In addition, we searched for retractions of EEoCs and affected
      articles in PubMed up to 8 December 2016. We analyzed overall historical trends,
      as well as reported reasons and subsequent editorial actions related to EEoCs
      issued between August 2014 and August 2016. RESULTS: After screening 5,076
      records, we identified 230 EEoCs that affect 300 publications indexed in PubMed,
      the earliest issued in 1985. Half of the primary EEoCs were issued between 2014
      and 2016 (52%). We found evidence of some EEoCs that had been removed by the
      publisher without leaving a record and some were not submitted for PubMed or PMC
      indexing. A minority of publications affected by EEoCs had been retracted by
      early December 2016 (25%). For the subset of 92 EEoCs issued between August 2014
      and August 2016, affecting 99 publications, the rate of retraction was similar
      (29%). The majority of EEoCs were issued because of concerns with validity of
      data, methods, or interpretation of the publication (68%), and 31% of cases
      remained open. Issues with images were raised in 40% of affected publications.
      Ongoing monitoring after the study identified another 17 EEoCs to year's end in
      2016, increasing the number of EEoCs to 247 and publications in PubMed known to
      be affected by EEoCs to 320 at the end of 2016. CONCLUSIONS: EEoCs have been rare
      publishing events in the biomedical literature, but their use has been
      increasing. Most have not led to retractions, and many remain unresolved. Lack of
      prominence and inconsistencies in management of EEoCs reduce the ability of these
      notices to alert the scientific community to potentially serious problems in
      publications. EEoCs will be made identifiable in PubMed in 2017.

PMID- 28758028
TI  - The interplay between genetic background and sexual dimorphism of doxorubicin
      induced cardiotoxicity.
AB  - BACKGROUND: Doxorubicin (DOX) is a very effective anticancer medication that is
      commonly used to treat hematological malignancies and solid tumors. Nevertheless,
      DOX is known to have cardiotoxic effects that may lead to cardiac dysfunction and
      failure. In experimental studies, female animals have been shown to be protected
      against DOX-induced cardiotoxicity; however, the evidence of this sexual
      dimorphism is inconclusive in clinical studies. Therefore, we sought to
      investigate whether genetic background could influence the sexual dimorphism of
      DOX-induced cardiotoxicity. METHODS: Male and female Wistar Kyoto (WKY) and
      Spontaneous Hypertensive Heart Failure (SHHF) rats were used. DOX was
      administered in eight doses of 2 mg/kg/week and the rats were followed for an
      additional 12 weeks. Cardiac function was assessed by trans-thoracic
      echocardiography, systolic blood pressure was measured by the tail cuff method,
      and heart and kidney tissues were collected for histopathology. RESULTS: Female
      sex protected against DOX-induced weight loss and increase in blood pressure in
      the WKY rats, whereas it protected against DOX-induced cardiac dysfunction and
      the elevation of cardiac troponin in SHHF rats. In both strains, female sex was
      protective against DOX-induced nephrotoxicity. There was a strong correlation
      between DOX-induced renal pathology and DOX-induced cardiac dysfunction.
      CONCLUSIONS: This study highlights the importance of studying the interaction
      between sex and genetic background to determine the risk of DOX-induced
      cardiotoxicity. In addition, our findings suggest that DOX-induced nephrotoxicity
      may play a role in DOX-induced cardiac dysfunction in rodent models.

PMID- 28758030
TI  - Relationship between Choroidal Thickness and Visual Field Impairment in Acute
      Zonal Occult Outer Retinopathy.
AB  - PURPOSE: To evaluate sequential changes in choroidal thickness at the affected
      area in patients with acute zonal occult outer retinopathy (AZOOR). METHODS: This
      retrospective observational case series included 14 affected eyes and 6
      unaffected fellow eyes from 10 AZOOR patients with impaired macular area. Using
      enhanced depth imaging optical coherence tomography, choroidal thicknesses at the
      subfovea and at nasal and temporal sites 1000 MUm away from the fovea were
      manually measured at baseline and 3 and 6 months thereafter. Changes in the
      choroidal thicknesses and the average threshold at the affected area on Humphrey
      perimetry were compared during the 6-month follow-up. RESULTS: In AZOOR eyes, the
      average threshold at the affected area significantly increased over time, while
      outer retinal structure ameliorated. The mean choroidal thicknesses at all the
      sites measured significantly decreased at 3 and 6 months compared with baseline
      values in AZOOR eyes, but not in fellow eyes. There was an inverse correlation
      between the changing rates of the average threshold and the subfoveal choroidal
      thickness at 6 months from baseline. CONCLUSION: The current data suggest that
      choroidal thickness at AZOOR-affected area significantly decreased with
      regression of AZOOR and this anatomical change correlated with the functional
      recovery.

PMID- 28758031
TI  - Comparison of Retinal Microvessel Blood Flow Velocities Acquired with Two
      Different Fields of View.
AB  - To compare the different retinal blood flow velocities (BFVs) acquired with
      different fields of view (FOVs) using the retinal function imager (RFI), twenty
      eyes of twenty healthy subjects were enrolled in the study. Retinal microvessel
      BFV in the macula was acquired with both a wide FOV (35 degrees, 7.3 * 7.3 mm2)
      and a commonly used small FOV (20 degrees, 4.3 * 4.3 mm2). The 35-degree FOV was
      trimmed to be equivalent to the 20-degree FOV to compare the BFVs of the similar
      FOVs using different settings. With the 35-degree FOV, both retinal arteriolar
      and venular BFVs were significantly greater than the 20-degree FOV (P < 0.001).
      When the 20-degree FOV was compared to the trimmed equivalent 20-degree FOV
      acquired using the 35-degree FOV, significant BFV differences were found in both
      the arterioles (P = 0.029) and venules (P < 0.001). This is the first study to
      compare retinal blood flow velocities acquired with different FOVs using RFI. The
      conversion factor from 35 degrees to 20 degrees is 0.95 for arteriolar BFV and
      0.92 for venular BFV, which may be used for comparing BFVs acquired with
      different FOVs.

PMID- 28758032
TI  - Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients
      with Familial Exudative Vitreoretinopathy.
AB  - Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized
      by incomplete development of the retinal vasculature. Here, we report the results
      obtained on the spectrum of genetic variations and correlated phenotypes found in
      a cohort of Italian FEVR patients. Eight probands (age range 7-19 years) were
      assessed by genetic analysis and comprehensive age-appropriate ophthalmic
      examination. Genetic testing investigated the genes most widely associated in
      literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic
      evaluations were extended to relatives of probands positive to genetic testing.
      Six out of eight probands (75%) showed a genetic variation probably related to
      the phenotype. We identified four novel genetic variants, one variant already
      described in association with Norrie disease and one previously described linked
      to autosomal dominant FEVR. Pedigree analysis of patients led to the
      classification of four autosomal dominant cases of FEVR (caused by FZD4 and
      TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the
      patients showed variants in the LRP5 gene. This study represents the largest
      cohort study in Italian FEVR patients. Our findings are in agreement with the
      previous literature confirming that FEVR is a clinically and genetically
      heterogeneous retinal disorder, even when it manifests in the same family.

PMID- 28758033
TI  - Efficacy and Tolerability of Intravenous Ferric Carboxymaltose in Patients with
      Iron Deficiency at a Hospital Outpatient Clinic: A Retrospective Cohort Study of
      Real-World Clinical Practice.
AB  - Ferric carboxymaltose (FCM) is an intravenous iron formulation to correct iron
      deficiency. Although its use has been extensively studied in clinical trials,
      real-world evidence regarding FCM treatment is scarce. Our aim was to evaluate
      the efficacy and tolerability of FCM treatment in patients with iron deficiency,
      with or without anemia, at a hospital outpatient clinic. Data was collected
      retrospectively from medical records. During this 2-year study, 459 patients were
      included. Mean age was 58.6 +/- 17.5 years and most patients received cumulative
      FCM doses of 501-1000 mg (63.2%). Six weeks after administration of FCM, efficacy
      endpoints hemoglobin increase >=2 g/dL, hemoglobin increase >=3 g/dL, and
      transferrin saturation > 20% were attained by 41%, 20%, and 63% of patients,
      respectively. Patients who received higher FCM doses showed significant reduced
      odds of not achieving hemoglobin increase >=2 g/dL (501-1000 mg, adjusted odds
      ratio [OR]: 0.34, 95% confidence interval [CI] 0.18-0.62; 1001-3000 mg, OR: 0.19,
      95% CI 0.07-0.49), compared to 500 mg doses. Treatment-emergent adverse events
      were documented in <4% of patients. In conclusion, FCM treatment was effective
      and well-tolerated by outpatients with iron deficiency at a hospital clinic, and
      its dosage should be adjusted to improve iron deficiency management in clinical
      practice.

PMID- 28758035
TI  - Selectable Implant Removal Methods due to Mechanical and Biological Failures.
AB  - Dental implant has been restoring the function and esthetics lost from missing
      tooth. However, biomechanical implant complications are the major cause of
      failing implants. Therefore, implant removal is one of the indispensable dental
      treatments. The 70-year-old male and 66-year-old female who had discomfort on
      posterior implants region came to Department of Periodontology. Conventional
      method using trephine bur and the new, nontraumatic method using a fixture
      removal kit were used for implant removal, respectively. Two different methods
      are commonly used for implant removal. Each has advantages and disadvantages;
      thus, the applied surgical method must consider a patient's intraoral condition,
      posttreatment plan, and the level of surgeon's skill and experience. In
      conclusion, strategically executing the most optimal implant removal method plays
      a pivotal role in maximizing the success rate of implant reinstallation that
      follows afterwards.

PMID- 28758034
TI  - Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by
      Oligomeric Amyloid-beta.
AB  - Amyloid-beta (Abeta) plays an important role in Alzheimer's disease (AD), as
      oligomeric Abeta induces loss of postsynaptic AMPA receptors (AMPARs) leading to
      cognitive deficits. The loss of postsynaptic AMPARs is mediated through the
      clathrin-dependent endocytosis pathway, in which endophilin2 is one of the
      important regulatory proteins. Endophilin2, which is enriched in both the pre-
      and postsynaptic membrane, has previously been reported to be important for
      recycling of synaptic vesicles at the presynaptic membrane. However, the role of
      endophilin2 in oligomeric Abeta-induced postsynaptic AMPAR endocytosis is not
      well understood. In this study, we show that endophilin2 does not affect
      constitutive AMPAR endocytosis. Endophilin2 knockdown, but not overexpression,
      resisted oligomeric Abeta-induced AMPAR dysfunction. Moreover, endophilin2
      colocalized and interacted with GluA1, a subunit of AMPAR, to regulate oligomeric
      Abeta-induced AMPAR endocytosis. Thus, we have determined a role of endophilin2
      in oligomeric Abeta-induced postsynaptic AMPAR dysfunction, indicating possible
      directions for preventing the loss of AMPARs in cognitive impairment and
      providing evidence for the clinical treatment of AD.

PMID- 28758036
TI  - Successful Endoscopic Treatment of Bouveret Syndrome in a Patient with
      Choledochoduodenal Fistula Complicating Duodenal Ulcer.
AB  - INTRODUCTION: Cholecystoduodenal fistulas represent the most common type of
      bilioenteric fistulas while choledochoduodenal fistulas account for only 1-25% of
      cases. Bilioenteric fistula cases are associated with cholelithiasis and are
      rarely associated with duodenal peptic ulcers. Here we present the first case of
      Bouveret syndrome secondary to choledochoduodenal fistula complicating peptic
      duodenal ulcer managed successfully via endoscopic mechanical lithotripsy. CASE:
      86-year-old male with a medical history significant for coronary artery disease
      and stage 3 colorectal cancer status after resection and chemoradiation presented
      with intractable sharp abdominal pain worse postprandially for one week in
      duration, associated with early satiety, anorexia, and 5 lbs weight loss in one
      week. CT abdomen showed possible choledochoduodenal fistula and a distended
      stomach. An esophagogastroduodenoscopy (EGD) was performed revealing a large 2.5
      3 cm stone lodged in the duodenal bulb at the base of duodenal ulcer with a
      fistula opening beneath it. The stone was extracted in 2 pieces via mechanical
      lithotripsy. Endoscopic ultrasound of the CBD revealed Rigler's triad.
      CONCLUSION: Bouveret syndrome is mostly associated with cholecystoduodenal
      fistula and has high mortality and morbidity due to underlying comorbid
      conditions and elderly age. Patients are not always fit for surgical management,
      and endoscopic management is not always successful.

PMID- 28758037
TI  - An Atypical Presentation of Chronic Atrophic Gastritis: Hemolytic Anemia and
      Mesenteric Panniculitis.
AB  - Microangiopathic hemolytic anemia (MAHA) requires an aggressive approach since
      primary thrombotic microangiopathy syndromes such as thrombotic thrombocytopenic
      purpura (TTP) can progress rapidly to a fatal outcome. Differential diagnosis can
      be challenging even for an experienced hematologist. We present a case of a 52
      year-old male who presented with symptoms of mesenteric panniculitis and showed
      signs of MAHA. His condition was attributed to severe vitamin B12 deficiency
      secondary to chronic atrophic gastritis and initiation of appropriate therapy was
      met with complete resolution of symptoms and normalization of hematologic
      parameters.

PMID- 28758038
TI  - Transient Central Diabetes Insipidus and Marked Hypernatremia following
      Cardiorespiratory Arrest.
AB  - Central Diabetes Insipidus is often an overlooked complication of cardiopulmonary
      arrest and anoxic brain injury. We report a case of transient Central Diabetes
      Insipidus (CDI) following cardiopulmonary arrest. It developed 4 days after the
      arrest resulting in polyuria and marked hypernatremia of 199 mM. The latter was
      exacerbated by replacing the hypotonic urine by isotonic saline.

PMID- 28758039
TI  - Primary Angiitis of the Center Nervous System: A Clinical Challenge Diagnosed
      Postmortem.
AB  - Primary angiitis of the central nervous system (PACNS) is a rare vasculitis
      involving medium and small blood vessels of the brain, spinal cord, and meninges,
      without systemic involvement. The diffuse and patchy nature of its pathology is
      reflected by a wide spectrum of nonspecific clinical symptoms. Diagnosis is
      challenging due to lack of defined clinical criteria or specific imaging
      findings. Specific workup should be done only after exclusion of other
      etiologies, including infectious, neoplastic, toxic, and other vascular
      etiologies including systemic vasculitis. Given the fact that it is a patchy
      disease with 25% of the biopsies being falsely negative, treating physician
      should have a high index of suspicion despite negative initial neurovascular
      imaging and biopsy results. Once diagnosed, early treatment with
      immunosuppressive therapy is essential to avoid permanent neurologic damage.
      Herein, we are reporting a case of 66-year-old female patient who presented with
      insidious onset right-sided frontal headache. Her hospital course progressively
      worsened and family decision based on her wishes was to refer her to hospice and
      comfort care. Despite an extensive workup with advanced imaging techniques, no
      diagnosis was established until postmortem autopsy and histopathology confirmed
      primary angiitis of the central nervous system.

PMID- 28758040
TI  - Repetitive Sinus-Related Symptoms May Accelerate the Progression of Chronic
      Maxillary Atelectasis.
AB  - Chronic maxillary atelectasis (CMA) is characterized by a progressive decrease in
      maxillary sinus volume. The factors that promote the stage progression of CMA
      remain poorly understood. Here, we describe the time course of anatomical changes
      in a 40-year-old woman with stage II CMA that progressed to stage III disease.
      She did not show stage progression until she started to develop repetitive sinus
      related symptoms. The stage progression was characterized by ocular symptoms. The
      repetitive inflammatory episodes may have increased the negative pressure in the
      affected sinus and weakened the bone walls, thereby promoting stage progression.
      Thus, a history of repetitive sinus-related symptoms may be a risk factor for
      stage progression in CMA.

PMID- 28758041
TI  - An Unusual Cause of Intestinal Obstruction in a Young Adult Patient: Inflammatory
      Fibroid Polyp.
AB  - Inflammatory fibroid polyps are uncommon benign lesions that originate in the
      submucosa of the gastrointestinal tract. The stomach and the ileum are the most
      commonly affected sites. Although inflammatory fibroid polyp is one of the rare
      conditions leading to intestinal obstruction in adults, it should be considered
      as a possible diagnosis in obstructive tumors of the small bowel causing
      intussusceptions. We present one case of inflammatory fibroid polyp as a rare
      cause of intussusception in a young adult patient.

PMID- 28758042
TI  - Small Bowel Obstruction Caused by Internal Hernia through a Peritoneal Defect of
      the Pouch of Douglas: Report of a Case and Review of the Literature.
AB  - Herniation of small bowel through the peritoneal defect of the Pouch of Douglas
      is extremely rare type of internal hernia, and this type of internal hernia has
      been described as an entity of perineal hernia. Here, we describe a case of a 26
      year-old female without history of abdominal surgery presenting with incarcerated
      small bowel hernia through a peritoneal defect of the Pouch of Douglas. She
      visited an emergency department presenting with abdominal pain and distension.
      Without improvement symptom by conservative management, an operation was
      performed. During the operation, the distal ileum had been herniated through a
      peritoneal defect of the Pouch of Douglas, and there were no specific findings on
      gynecological examination. Reduction of the herniated bowel and primary repair of
      the peritoneal defect were performed. The case represents a very rare type of
      internal hernia and provides published cases of hernia through a peritoneal
      defect of the Pouch of Douglas.

PMID- 28758043
TI  - Multiple Acrometastases in a Patient with Renal Pelvic Urothelial Cancer.
AB  - Metastasis may occur in any bone but more commonly occurs in the spine, pelvis,
      or other axial bones. Metastasis in peripheral bones located distal to the elbow
      or knee, so-called acrometastasis, is rare. Although the mechanism of
      acrometastasis development is not completely understood, it is thought to be the
      result of a massive dissemination of cancer cells; thus the prognosis of patients
      with acrometastasis is relatively poor. Here, we report the case of renal pelvic
      cancer with multiple acrometastases in both the upper and lower extremities
      without axial bone metastasis in a 68-year-old man. After two regimens of
      chemotherapy, he suffered from pain on his wrist and ankle and swelling and
      hemorrhage of his toe. He had no axial bone metastasis by CT but was diagnosed
      with multiple acrometastases by plain radiographs. Radiation therapy and
      disarticulation of the left big toe at the metacarpal-phalangeal joint were
      performed and his pain and hemorrhage were successfully controlled. Although
      acrometastasis from renal pelvic cancer is very rare, we should recognize that
      acrometastasis might occur which exists outside of the CT scanning field.

PMID- 28758045
TI  - Linear Time Algorithms to Restrict Insider Access using Multi-Policy Access
      Control Systems.
AB  - An important way to limit malicious insiders from distributing sensitive
      information is to as tightly as possible limit their access to information. This
      has always been the goal of access control mechanisms, but individual approaches
      have been shown to be inadequate. Ensemble approaches of multiple methods
      instantiated simultaneously have been shown to more tightly restrict access, but
      approaches to do so have had limited scalability (resulting in exponential
      calculations in some cases). In this work, we take the Next Generation Access
      Control (NGAC) approach standardized by the American National Standards Institute
      (ANSI) and demonstrate its scalability. The existing publicly available reference
      implementations all use cubic algorithms and thus NGAC was widely viewed as not
      scalable. The primary NGAC reference implementation took, for example, several
      minutes to simply display the set of files accessible to a user on a moderately
      sized system. In our approach, we take these cubic algorithms and make them
      linear. We do this by reformulating the set theoretic approach of the NGAC
      standard into a graph theoretic approach and then apply standard graph
      algorithms. We thus can answer important access control decision questions (e.g.,
      which files are available to a user and which users can access a file) using
      linear time graph algorithms. We also provide a default linear time mechanism to
      visualize and review user access rights for an ensemble of access control
      mechanisms. Our visualization appears to be a simple file directory hierarchy but
      in reality is an automatically generated structure abstracted from the underlying
      access control graph that works with any set of simultaneously instantiated
      access control policies. It also provide an implicit mechanism for symbolic
      linking that provides a powerful access capability. Our work thus provides the
      first efficient implementation of NGAC while enabling user privilege review
      through a novel visualization approach. This may help transition from concept to
      reality the idea of using ensembles of simultaneously instantiated access control
      methodologies, thereby limiting insider threat.

PMID- 28758044
TI  - Deep Brain Stimulation of Hemiparkinsonian Rats with Unipolar and Bipolar
      Electrodes for up to 6 Weeks: Behavioral Testing of Freely Moving Animals.
AB  - Although the clinical use of deep brain stimulation (DBS) is increasing, its
      basic mechanisms of action are still poorly understood. Platinum/iridium
      electrodes were inserted into the subthalamic nucleus of rats with unilateral 6
      OHDA-induced lesions of the medial forebrain bundle. Six behavioral parameters
      were compared with respect to their potential to detect DBS effects. Locomotor
      function was quantified by (i) apomorphine-induced rotation, (ii) initiation
      time, (iii) the number of adjusting steps in the stepping test, and (iv) the
      total migration distance in the open field test. Sensorimotor neglect and anxiety
      were quantified by (v) the retrieval bias in the corridor test and (vi) the ratio
      of migration distance in the center versus in the periphery in the open field
      test, respectively. In our setup, unipolar stimulation was found to be more
      efficient than bipolar stimulation for achieving beneficial long-term DBS
      effects. Performance in the apomorphine-induced rotation test showed no
      improvement after 6 weeks. DBS reduced the initiation time of the contralateral
      paw in the stepping test after 3 weeks of DBS followed by 3 weeks without DBS.
      Similarly, sensorimotor neglect was improved. The latter two parameters were
      found to be most appropriate for judging therapeutic DBS effects.

PMID- 28758046
TI  - Medical Question Answering for Clinical Decision Support.
AB  - The goal of modern Clinical Decision Support (CDS) systems is to provide
      physicians with information relevant to their management of patient care. When
      faced with a medical case, a physician asks questions about the diagnosis, the
      tests, or treatments that should be administered. Recently, the TREC-CDS track
      has addressed this challenge by evaluating results of retrieving relevant
      scientific articles where the answers of medical questions in support of CDS can
      be found. Although retrieving relevant medical articles instead of identifying
      the answers was believed to be an easier task, state-of-the-art results are not
      yet sufficiently promising. In this paper, we present a novel framework for
      answering medical questions in the spirit of TREC-CDS by first discovering the
      answer and then selecting and ranking scientific articles that contain the
      answer. Answer discovery is the result of probabilistic inference which operates
      on a probabilistic knowledge graph, automatically generated by processing the
      medical language of large collections of electronic medical records (EMRs). The
      probabilistic inference of answers combines knowledge from medical practice
      (EMRs) with knowledge from medical research (scientific articles). It also takes
      into account the medical knowledge automatically discerned from the medical case
      description. We show that this novel form of medical question answering (Q/A)
      produces very promising results in (a) identifying accurately the answers and (b)
      it improves medical article ranking by 40%.

PMID- 28758047
TI  - The Role of the Ikaros Family of Transcription Factors in Regulatory T cell
      Development and Function.
AB  - Regulatory T (Treg) cells are a subset of immune cells that maintain homeostasis
      by promoting immune tolerance and suppressing the immune response via a variety
      of mechanisms such as secreting cytokines, killing reactive immune cells, and
      inducing anergy. Dysfunction of Treg cells has been implicated in inflammatory
      diseases such as autoimmunity and transplant rejection. Conversely, too many or
      hyperresponsive Treg cells has been observed in cancer and chronic infections.
      Treg cells have proven to be difficult to study as there are no definitive Treg
      surface markers. Additionally, Tregs can gain pro-inflammatory phenotype
      depending on stimuli. In this commentary, we discuss the expression and function
      of members of the Ikaros family of transcription factors during Treg cell
      development and activation.

PMID- 28758048
TI  - Fulminant Mycosis Fungoides with Tissue Eosinophilia: A Unique Presentation of
      Two Cases with Acro-Periorbital Ulceration and An Aggressive Clinical Course.
AB  - We describe two unique cases of fulminant mycosis fungoides with remarkably
      similar and aggressive clinical courses resulting in death. Both cases
      demonstrated ulcerated palmar and periorbital plaques and marked tissue
      eosinophilia, which was confirmed by T-cell receptor gamma chain gene
      rearrangement studies to display identical monoclonality at temporally and
      anatomically distinct sites. Dense eosinophilic infiltrates on biopsy led to
      misdiagnosis of inflammatory dermatoses in both instances. While mycosis
      fungoides may be challenging to diagnose histologically, the presence of
      eosinophils in progressive disease may herald a poor prognosis and should not
      exclude the diagnosis.

PMID- 28758049
TI  - Artifacts in magnetic measurements of fluid samples.
AB  - Applications of magnetic fluids are ever increasing, as well as the corresponding
      need to be able to characterize these fluids in situ. Commercial magnetometers
      are accurate and well-characterized for solid and powder samples, but their use
      with fluid samples is more limited. Here, we describe artifacts which can occur
      in magnetic measurements of fluid samples and their impact. The most critical
      problem in the measurement of fluid samples is the dynamic nature of the sample
      position and size/shape. Methods to reduce these artifacts are also discussed,
      such as removal of air bubbles and dynamic centering.

PMID- 28758050
TI  - A LEGISLATIVE CASE STUDY OF THE EVOLUTION OF POLYVICTIMIZATION RESEARCH AND
      POLICY IMPLEMENTATION: MENTAL HEALTH PROFESSIONALS' DUTY TO ENGAGE IN PUBLIC
      POLICY ADVOCACY.
AB  - One reason that scientific research takes so long to reach patients is that
      medical researchers and practitioners often lack training in public policy
      implementation theory and strategy. General medical and specific psychiatric
      ethical precepts in the United States and in international ethics codes invest
      public policy duties in psychiatric researchers and individual clinicians. This
      essay discusses those medical ethical rules and suggests means for training
      psychiatrists to meet their public health policy duties in legal fora. The
      discussion presents a case study of the evolution of polyvictimization research,
      its initial lack of implementation in clinical practice and public policy
      debates, and a detailed demonstration of the incorporation of polyvictimization
      research in informing legislative action. Through systematic efforts to expand
      training and involvement of psychiatrists, we can expedite the implementation of
      psychiatric research by marshalling individual psychiatrists to affect decisions
      in legislative, executive, and judicial proceedings. These individual efforts can
      occur synergistically with ongoing psychiatric and psychological organizations'
      efforts to better effect timely incorporation of evidence-based policies to
      improve mental health at the local, state, national, and international levels.

PMID- 28758051
TI  - Serotonin in the Frontal Cortex: A Potential Therapeutic Target for Neurological
      Disorders.

PMID- 28758052
TI  - Role of MicroRNA in Osteoarthritis.
AB  - Although the potential effect of aberrant expression of catabolic and anabolic
      genes on the development of osteoarthritis (OA) is well-documented, the
      regulatory mechanism for the expression of these genes in articular chondrocytes
      remains to be elucidated. The recent advances in epigenetic studies have
      identified microRNA (miRNA) as one of the epigenetic mechanisms for the
      regulation of gene expression. This mini review highlights the role of miRNA in
      the regulation of gene expression in articular chondrocytes and its significance
      in the pathogenesis of OA, with a discussion on the potential of miRNA as a new
      biomarker and therapeutic target for OA. Further investigations are required to
      determine the specificity, sensitivity, and efficacy of miRNA for clinical
      applications.

PMID- 28758053
TI  - Carvedilol inhibits cADPR- and IP3-induced Ca2+ release.
AB  - Spontaneous Ca2+ waves, also termed store-overload-induced Ca2+ release (SOICR),
      in cardiac cells can trigger ventricular arrhythmias especially in failing
      hearts. SOICR occurs when RyRs are activated by an increase in sarcoplasmic
      reticulum (SR) luminal Ca2+. Carvedilol is one of the most effective drugs for
      preventing arrhythmias in patients with heart failure. Furthermore, carvedilol
      analogues with minimal beta-blocking activity also block SOICR showing that SOICR
      inhibiting activity is distinct from that for beta-block. We show here that
      carvedilol is a potent inhibitor of cADPR-induced Ca2+ release in sea urchin egg
      homogenate. In addition, the carvedilol analog VK-II-86 with minimal beta
      blocking activity also suppresses cADPR-induced Ca2+ release. Carvedilol appeared
      to be a non-competitive antagonist of cADPR and could also suppress Ca2+ release
      by caffeine. These results are consistent with cADPR releasing Ca2+ in sea urchin
      eggs by sensitizing RyRs to Ca2+ involving a luminal Ca2+ activation mechanism.
      In addition to action on the RyR, we also observed inhibition of inositol 1,4,5
      trisphosphate (IP3)-induced Ca2+ release by carvedilol suggesting a common
      mechanism between these evolutionarily related and conserved Ca2+ release
      channels.

PMID- 28758054
TI  - Instance Search Retrospective with Focus on TRECVID.
AB  - This paper presents an overview of the Video Instance Search benchmark which was
      run over a period of 6 years (2010-2015) as part of the TREC Video Retrieval
      (TRECVID) workshop series. The main contributions of the paper include i) an
      examination of the evolving design of the evaluation framework and its components
      (system tasks, data, measures); ii) an analysis of the influence of topic
      characteristics (such as rigid/non rigid, planar/non-planar, stationary/mobile on
      performance; iii) a high-level overview of results and best-performing
      approaches. The Instance Search (INS) benchmark worked with a variety of large
      collections of data including Sound & Vision, Flickr, BBC (British Broadcasting
      Corporation) Rushes for the first 3 pilot years and with the small world of the
      BBC Eastenders series for the last 3 years.

PMID- 28758055
TI  - Diagnosis is a team sport - partnering with allied health professionals to reduce
      diagnostic errors: A case study on the role of a vestibular therapist in
      diagnosing dizziness.
AB  - BACKGROUND: Diagnostic errors are the most common, most costly, and most
      catastrophic of medical errors. Interdisciplinary teamwork has been shown to
      reduce harm from therapeutic errors, but sociocultural barriers may impact the
      engagement of allied health professionals (AHPs) in the diagnostic process.
      METHODS: A qualitative case study of the experience at a single institution
      around involvement of an AHP in the diagnostic process for acute dizziness and
      vertigo. We detail five diagnostic error cases in which the input of a physical
      therapist was central to correct diagnosis. We further describe evolution of the
      sociocultural milieu at the institution as relates to AHP engagement in
      diagnosis. RESULTS: Five patients with acute vestibular symptoms were initially
      misdiagnosed by physicians and then correctly diagnosed based on input from a
      vestibular physical therapist. These included missed labyrinthine concussion and
      post-traumatic benign paroxysmal positional vertigo (BPPV); BPPV called
      gastroenteritis; BPPV called stroke; stroke called BPPV; and multiple sclerosis
      called BPPV. As a consequence of surfacing these diagnostic errors, initial
      resistance to physical therapy input to aid medical diagnosis has gradually
      declined, creating a more collaborative environment for 'team diagnosis' of
      patients with dizziness and vertigo at the institution. CONCLUSIONS: Barriers to
      AHP engagement in 'team diagnosis' include sociocultural norms that establish
      medical diagnosis as something reserved only for physicians. Drawing attention to
      the valuable diagnostic contributions of AHPs may help facilitate cultural
      change. Future studies should seek to measure diagnostic safety culture and then
      implement proven strategies to breakdown sociocultural barriers that inhibit
      effective teamwork and transdisciplinary diagnosis.

PMID- 28758056
TI  - Single-Cell Transcriptome Analysis of Developing and Regenerating Spiral Ganglion
      Neurons.
AB  - The spiral ganglion neurons (SGNs) of the cochlea are essential for our ability
      to hear. SGN loss after exposure to ototoxic drugs or loud noise results in
      hearing loss. Pluripotent stem cell-derived and endogenous progenitor cell types
      have the potential to become SGNs and are cellular foundations for replacement
      therapies. Repurposing transcriptional regulatory networks to promote SGN
      differentiation from progenitor cells is a strategy for regeneration. Advances in
      the Fludigm C1 workflow or Drop-seq allow sequencing of single cell
      transcriptomes to reveal variability between cells. During differentiation, the
      individual transcriptomes obtained from single-cell RNA-seq can be exploited to
      identify different cellular states. Pseudotemporal ordering of transcriptomes
      describes the differentiation trajectory, allows monitoring of transcriptional
      changes and determines molecular barriers that prevent the progression of
      progenitors into SGNs. Analysis of single cell transcriptomes will help develop
      novel strategies for guiding efficient SGN regeneration.

PMID- 28758057
TI  - The Opportunities of Metabolomics in Drug Safety Evaluation.
AB  - Although safety of drug candidates is carefully monitored in preclinical and
      clinical studies using a variety of approaches, drug toxicity may still occur in
      clinical practice. Therefore, novel approaches are needed to complement the
      current drug safety evaluation system. Metabolomics comprehensively analyzes the
      metabolites altered by drug exposure, which can therefore be used to profile drug
      metabolism, endobiotic metabolism, and drug-microbiota interactions. The
      information from metabolomic analysis can be used to determine the off-targets of
      a drug candidate, and thus provide a mechanistic understanding of drug toxicity.
      We herein discuss the opportunities of metabolomics in drug safety evaluation.

PMID- 28758058
TI  - Clinical Usefulness of Cardio-ankle Vascular Index, Local Artery Carotid
      Stiffness and Global Longitudinal Strain in Subjects with Cardiovascular Risk
      Factors.

PMID- 28758059
TI  - Hypertension and Diabetes Mellitus: How Do They Affect the Right Ventricular
      Functions Individually and Together?
AB  - CONTEXT: The right ventricle (RV) is neglected in clinical practice although the
      RV function is the primary determinant of prognosis and effort tolerance in many
      groups of patients. AIM: The effects of type two diabetes mellitus and
      hypertension solitary and together were studied on right ventricular systolic and
      diastolic function by echo-Doppler and tissue Doppler echocardiography. SETTINGS
      AND DESIGN: A cohort of 300 consecutive patients with echocardiographic right
      ventricular (RV) diastolic dysfunction as determined by Doppler echocardiography
      were included in this study. METHODS AND MATERIAL: Patients were divided in four
      groups, patients who were neither diabetic nor hypertensive, hypertensive
      patients, diabetic patients and those patients suffering from both hypertension
      and diabetes mellitus. Parameters of right ventricular systolic and diastolic
      function were compared. STATISTICAL ANALYSIS USED: Analyses were performed with
      SPSS version 12.0 statistical package (SPSS Inc., Chicago, IL, USA). RESULTS:
      There was significant statistical difference between the four groups as regards E
      wave, E/A ratio and deceleration time measured by Doppler echocardiography. By
      pulsed wave tissue Doppler, S, E' and E/E' showed significant statistical
      difference between the four groups. All of these parameters were significantly
      different between the group suffering from both diseases and the group who had
      neither of them. CONCLUSIONS: The combined effect of both, diabetes mellitus and
      hypertension on right ventricular function is stronger than the effect of one of
      them alone.

PMID- 28758061
TI  - ST-elevation Myocardial Infarction: An Unusual Presentation of Infective
      Endocarditis.
AB  - Acute coronary syndrome is an uncommon complication in patients with infective
      endocarditis, either in the acute phase of infection or later in the course. We
      describe a case of unusual presentation of infective endocarditis as ST-elevation
      myocardial infarction secondary to coronary embolization from mitral valve
      endocarditis.

PMID- 28758060
TI  - Early Speckle-tracking Echocardiography Predicts Left Ventricle Remodeling after
      Acute ST-segment Elevation Myocardial Infarction.
AB  - BACKGROUND: Prediction of the left ventricular remodeling (LVR) after ST-segment
      elevation myocardial infarction (STEMI) in patients treated with effective
      myocardial reperfusion is challenging. METHODS: Forty-one consecutive patients
      (36 males, age 59 +/- 10 years) with STEMI who underwent effective (TIMI III)
      primary coronary angioplasty were enrolled. All patients had an echocardiography
      and cardiac magnetic resonance (CMR) study within 72 h from revascularization.
      Three echocardiographic parameters including LV ejection fraction (EF), global
      longitudinal strain (GLS) and severe altered longitudinal strain (SAS) area by
      two-dimensional speckle-tracking echocardiography (2D-STE) and 3 CMR indices
      including LV global function index (LV-GFI), myocardial salvage index (MSI), and
      microvascular obstruction (MVO) were calculated. LVR was defined as an increase
      in CMR LV end-diastolic volume (EDV) >15% after 6 months. RESULTS: Of 41
      patients, 10 (24%) had LVR (LV-EDV from 145.1 +/- 29.3 to 185.9 +/- 49.8 ml, P <
      0.001). A significant correlation with LV-EDV variation was found for baseline
      SAS area (r = 0.81), LV-GFI (r = -0.56), MVO (r = 0.55), EF (r = -0.42), GLS (r =
      0.42), not for MSI (r = -0.25). At the multivariable analysis, a significant
      correlation remained only for the SAS area. The receiver-operating characteristic
      curve analysis showed that a baseline SAS area >=15% predicts LVR with a
      sensitivity of 80.0% and a specificity of 90.3%. CONCLUSIONS: The SAS area
      evaluated by 2D-STE early in acute STEMI is a valuable predictor of LVR after 6
      months. Further investigations are needed to verify its value in predicting
      patient survival.

PMID- 28758062
TI  - Left Ventricular Outflow Tract Thrombus in a Child with Dilated Cardiomyopathy:
      An Atypical Location.
AB  - Dilated cardiomyopathy (DCM) may be associated with formation of intracardiac
      thrombi which may embolize and result in life-threatening complications. We
      present a 19-month-old female child with DCM who presented with a right
      hemispheric cerebrovascular accident. Urgent echocardiography revealed poor left
      ventricular systolic function and a thrombus attached to the interventricular
      septum along the left ventricular outflow tract. There was resolution of the
      thrombus following the use of warfarin.

PMID- 28758063
TI  - Acquired Systemic-to-pulmonary Venous Shunt or Persistent Left Superior Vena
      Cava? A Rare Right-to-left Shunt Case-based Discussion.
AB  - Cardiac shunts are often described in congenital or pediatric populations, but
      systemic-to-pulmonary venous shunts in adult patients are reported in literature
      in isolated case reports. We present the case of a 70-year-old female with a left
      superior vena cava (SVC) draining into the left atrium by the left superior
      pulmonary vein, with a complete right-to-left shunt of the superior venous
      circulation caused by a former catheter thrombosis in the right SVC. Diagnosis
      was suspected after a contrast echocardiography showing an exclusive perfusion of
      left heart after intravenous injection and confirmed by helical computed
      tomography with three-dimensional reconstruction. After medico-surgical
      discussion, a first-line conservative treatment with oxygen therapy was chosen,
      due to the stability of symptoms and high predicted risk of perioperative
      mortality. The particularities of this case are that we cannot determine if the
      origin of this shunt is a latent persistent left SVC becoming symptomatic after
      the SVC obstruction or an abnormal collateral pathway due to the thrombosis and
      the unusual indirect communication through a pulmonary vein.

PMID- 28758064
TI  - Bifurcated Great Saphenous Vein: A Report on Its Therapeutic and Diagnostic
      Perspectives.
AB  - The great saphenous vein (GSV) is the longest superficial vein in the body
      extending from the medial malleolus to groin skin crease level. The clinical
      usage of GSV has made its anatomical variations noteworthy. Since many
      tributaries accompany it, GSV is often mistaken with the variant vein.
      Duplication and persistence of accessory GSV are the two major clinically
      significant anatomical variations of the GSV which is frequently misinterpreted
      as a synonym. In the present case, we report a unique variation of GSV wherein it
      bifurcated into anterior and posterior divisions of two uneven calibers at knee
      region, which then reunited at thigh region to form a single vein before its
      termination into the femoral vein. Locating such variations of bifurcated GSV is
      a challenging task for both diagnostic and therapeutic tactics, particularly in
      venography procedures as it might lead to iatrogenic traumatic injury of the
      vessel.

PMID- 28758065
TI  - What Ultrasounds, Sometimes, Cannot See: A Case of Posterior Pericardial Cyst.
AB  - Pericardial cysts (PCs) are very rare, often congenital, mediastinal masses.
      Usually, they are located in the right cardiophrenic angle and only in 8% of
      cases in the anterior or posterior mediastinum. Computed tomography and/or
      magnetic resonance imaging are accurate tools for the diagnosis and
      characterization of mediastinal masses. However, echocardiography is, in many
      cases, a good screening technique. If asymptomatic, they do not require surgical
      excision. The authors describe a case of posterior mediastinum PC; in these
      cases, echocardiography cannot see the mass and three-dimensional imaging
      techniques are required. The clinical management of this case is discussed.

PMID- 28758066
TI  - Subsequent Safe Pregnancy with Cesarean Delivery in a Patient with a History of
      Peripartum Takotsubo Syndrome Complicated by Cardiogenic Shock.
AB  - Takotsubo syndrome (TTS) is an acute and reversible heart failure syndrome,
      usually occurring in females but rarely in the peripartum period. In women with a
      history of peripartum TTS, it is unclear how to manage subsequent pregnancies. A
      39-year-old female with a history of peripartum TTS complicated by cardiogenic
      shock became pregnant again. She underwent close cardiological follow-up for
      monitoring left ventricular systolic function and hemodynamic conditions.
      Epidural anesthesia was preferred to avoid catecholamine surge during cesarean
      delivery. After a few days of hospitalization, the patient and the newborn were
      discharged in good health. In our patient with a history of complicated
      peripartum TTS, close cardiological follow-up, appropriate management therapy,
      and anesthesia modality allow us to guide safely a new pregnancy.

PMID- 28758067
TI  - Left Atrial Morphology and Function: A Strong Cardiovascular Predictor of
      Outcome.

PMID- 28758068
TI  - Have the Olympic Games become more migratory? A comparative historical
      perspective.
AB  - It is often believed that the Olympic Games have become more migratory. The
      number of Olympic athletes representing countries in which they weren't born is
      thought to be on the rise. It should, however, be noted that migration in the
      context of sports is hardly a new phenomenon. In this paper we hypothesise that,
      as a reflection of global migration patterns and trends, the number of foreign
      born Olympians hasn't necessarily increased in all countries. Furthermore, it was
      expected that the direction of Olympic migration has changed and that foreign
      athletes increasingly come from a more diverse palette of countries. We conducted
      an analysis of approximately 40,000 participants from 11 countries who
      participated in the Summer Games between 1948 and 2012. The selected countries
      have different histories of migration and cover the distinction between 'nations
      of immigrants' (Australia, Canada, United States), 'countries of immigration'
      (France, Great Britain, Netherlands, Sweden), 'latecomers to immigration' (Italy,
      Spain) and, what we coin, 'former countries of immigration' (Argentina, Brazil).
      We conclude that the Olympic Games indeed have not become inherently more
      migratory. Rather, the direction of Olympic migration has changed and most teams
      have become more diverse. Olympic migration is thus primarily a reflection of
      global migration patterns instead of a discontinuity with the past.

PMID- 28758069
TI  - Investigating the application of a nitroreductase-expressing transgenic zebrafish
      line for high-throughput toxicity testing.
AB  - Nitroreductase enzymes are responsible for the reduction of nitro functional
      groups to amino functional groups, and are found in a range of animal models,
      zebrafish (Danio rerio) excluded. Transgenic zebrafish models have been developed
      for tissue-specific cell ablation, which use nitroreductase to ablate specific
      tissues or cell types following exposure to the non-toxic pro-drug metronidazole
      (MTZ). When metabolized by nitroreductase, MTZ produces a potent cytotoxin, which
      specifically ablates the tissue in which metabolism occurs. Uses, beyond tissue
      specific cell ablation, are possible for the hepatocyte-specific Tg(l-fabp:CFP
      NTR)s891 zebrafish line, including investigations of the role of nitroreductase
      in the toxicity of nitrated compounds. The hepatic ablation characteristics of
      this transgenic line were explored, in order to expand its potential uses.
      Embryos were exposed at 48, 72, or 96 hours post fertilization (hpf) to a range
      of MTZ concentrations, and the ablation profiles were compared. Ablation occurred
      at a 10-fold lower concentration than previously reported. Embryos were exposed
      to a selection of other compounds, with and without MTZ, in order to investigate
      alternative uses for this transgenic line. Test compounds were selected based on:
      their ability to undergo nitroreduction, known importance of hepatic metabolism
      to toxicity, and known pharmaceutical hepatotoxins. Selected compounds included
      nitrated polycyclic aromatic hydrocarbons (nitro-PAHs), the PAHs retene and
      benzo[a]pyrene, and the pharmaceuticals acetaminophen and flutamide. The results
      suggest a range of potential roles of the liver in the toxicity of these
      compounds, and highlight the additional uses of this transgenic model in toxicity
      testing.

PMID- 28758070
TI  - Prediction of Post-stroke Falls by Quantitative Assessment of Balance.
AB  - OBJECTIVE: To evaluate characteristics of the postural instability in patients
      with stroke and to present a prediction model of post-stroke falls. METHODS:
      Patients with a first-ever stroke who had been evaluated by the Balance Master
      (BM) at post-stroke 3 months (+/-1 month) between August 2011 and December 2015
      were enrolled. Parameters for the postural instability, such as the weight
      bearing asymmetry (WBA) and postural sway velocity (PSV), were obtained. The fall
      events in daily lives were assessed via structured telephone interview with a
      fall related questionnaire. RESULTS: A total of 71 patients (45 men; 45 with
      ischemic stroke) were enrolled in this study. All subjects underwent BM
      evaluation at 3.03+/-0.40 months after stroke. The mean WBA was 17.18%+/-13.10%
      and mean PSV (measured as  degrees /s) were noted as 0.66+/-0.37 (eyes-open on
      firm surface), 0.89+/-0.75 (eyes-closed on firm surface), 1.45+/-1.09 (eyes-open
      on soft surface), and 3.10+/-1.76 (eyes-closed on soft surface). A prediction
      model of post-stroke falls was drawn by multiple logistic regression analysis as
      follows: Risk of post-stroke falls = -2.848 + 1.878 x (PSVECSS) + 0.154 x (age=1
      if age>=65; age=0 if age<65). CONCLUSION: The weight bearing asymmetry and
      postural sway were significantly increased in patients with stroke. Older age and
      impaired postural control increased the risk of post-stroke falls.

PMID- 28758071
TI  - Effects of Mirror Therapy Using a Tablet PC on Central Facial Paresis in Stroke
      Patients.
AB  - OBJECTIVE: To investigate the effects of mirror therapy using a tablet PC for
      post-stroke central facial paresis. METHODS: A prospective, randomized controlled
      study was performed. Twenty-one post-stroke patients were enrolled. All patients
      performed 15 minutes of orofacial exercise twice daily for 14 days. The mirror
      group (n=10) underwent mirror therapy using a tablet PC while exercising, whereas
      the control group (n=11) did not. All patients were evaluated using the Regional
      House-Brackmann Grading Scale (R-HBGS), and the length between the corner of the
      mouth and the ipsilateral earlobe during rest and smiling before and after
      therapy were measured bilaterally. We calculated facial movement by subtracting
      the smile length from resting length. Differences and ratios between bilateral
      sides of facial movement were evaluated as the final outcome measure. RESULTS:
      Baseline characteristics were similar for the two groups. There were no
      differences in the scores for the basal Modified Barthel Index, the Korean
      version of Mini-Mental State Examination, National Institutes of Health Stroke
      Scale, R-HBGS, and bilateral differences and ratios of facial movements. The R
      HBGS as well as the bilateral differences and ratios of facial movement showed
      significant improvement after therapy in both groups. The degree of improvement
      of facial movement was significantly larger in the mirror group than in the
      control group. CONCLUSION: Mirror therapy using a tablet PC might be an effective
      tool for treating central facial paresis after stroke.

PMID- 28758072
TI  - Effects of Early Cranioplasty on the Restoration of Cognitive and Functional
      Impairments.
AB  - OBJECTIVE: To delineate the effect of early cranioplasty on the recovery of
      cognitive and functional impairments in patients who received decompressive
      craniectomy after traumatic brain injury or spontaneous cerebral hemorrhage.
      METHODS: Twenty-four patients who had received cranioplasty were selected and
      divided according to the period from decompressive craniectomy to cranioplasty
      into early (<=90 days) and late (>90 days) groups. The Korean version of the Mini
      Mental State Examination (K-MMSE), Korean version of the Modified Barthel Index
      (K-MBI), and Functional Independence Measure (FIM) were evaluated at admission
      just after decompressive craniectomy and during the follow-up period after
      cranioplasty. RESULTS: Twelve patients were included in the early group, and
      another 13 patients were included in the late group. The age, gender, type of
      lesion, and initial K-MMSE, K-MBI, and FIM did not significantly differ between
      two groups. However, the total gain scores of the K-MMSE and FIM in the early
      group (4.50+/-7.49 and 9.42+/-15.96, respectively) increased more than those in
      the late group (-1.08+/-3.65 and -0.17+/-17.86, respectively), and some of K-MMSE
      subscores (orientation and language) and FIM subcategories (self-care and
      transfer-locomotion) in the early group increased significantly when compared to
      those in the late group without any serious complications. We also found that the
      time to perform a cranioplasty was weakly, negatively correlated with the K-MMSE
      gain score (r=-0.560). CONCLUSION: Early cranioplasty might be helpful in
      restoring cognitive and functional impairments, especially orientation, language
      ability, self-care ability, and mobility in patients with traumatic brain injury
      or spontaneous cerebral hemorrhage.

PMID- 28758073
TI  - The Korean Version of the Cognitive Assessment Scale for Stroke Patients (K
      CASP): A Reliability and Validity Study.
AB  - OBJECTIVE: To develop the Korean version of the Cognitive Assessment Scale for
      Stroke Patients (K-CASP) and to evaluate the test reliability and validity of the
      K-CASP in stroke patients. METHODS: The original CASP was translated into Korean,
      back-translated into English, then reviewed and compared with the original
      version. Thirty-three stroke patients were assessed independently by two
      examiners using the K-CASP twice, with a one-day interval, for a total of four
      test results. To evaluate the reliability of the K-CASP, intra-class correlation
      coefficients were used. Pearson correlations were calculated and simple
      regression analyses performed with the Korean version of Mini-Mental State
      Examination (K-MMSE) and the aphasia quotient (AQ) to assess the validity.
      RESULTS: The mean score was 24.42+/-9.47 (total score 36) for the K-CASP and
      21.50+/-7.01 (total score 30) for the K-MMSE. The inter-rater correlation
      coefficients of the K-CASP were 0.992 on the first day and 0.995 on the second
      day. The intra-rater correlation coefficients of the K-CASP were 0.997 for
      examiner 1 and 0.996 for examiner 2. In the Pearson correlation analysis, the K
      CASP score significantly correlated with the K-MMSE score (r=0.825, p<0.001). The
      coefficients of determination (r2) of the AQ were 0.586 for the K-MMSE and 0.513
      for the K-CASP in the simple regression analysis. CONCLUSION: The K-CASP is a
      reliable and valid instrument for cognitive dysfunction screening in post-stroke
      patients. It is more applicable than other cognitive assessment tools in stroke
      patients with aphasia.

PMID- 28758074
TI  - Efficacy of Aquatic Treadmill Training on Gait Symmetry and Balance in Subacute
      Stroke Patients.
AB  - OBJECTIVE: To determine the efficacy of aquatic treadmill training (ATT) as a new
      modality for stroke rehabilitation, by assessing changes in gait symmetry,
      balance function, and subjective balance confidence for the paretic and non
      paretic leg in stroke patients. METHODS: Twenty-one subacute stroke patients
      participated in 15 intervention sessions of aquatic treadmill training. The
      Comfortable 10-Meter Walk Test (CWT), spatiotemporal gait parameters, Berg
      Balance Scale (BBS), and Activities-specific Balance Confidence scale (ABC) were
      assessed pre- and post-interventions. RESULTS: From pre- to post-intervention,
      statistically significant improvements were observed in the CWT (0.471+/-0.21 to
      0.558+/-0.23, p<0.001), BBS (39.66+/-8.63 to 43.80+/-5.21, p<0.001), and ABC
      (38.39+/-13.46 to 46.93+/-12.32, p<0.001). The step-length symmetry (1.017+/-0.25
      to 0.990+/-0.19, p=0.720) and overall temporal symmetry (1.404+/-0.36 to 1.314+/
      0.34, p=0.218) showed improvement without statistical significance. CONCLUSION:
      ATT improves the functional aspects of gait, including CWT, BBS and ABC, and
      spatiotemporal gait symmetry, though without statistical significance. Further
      studies are required to examine and compare the potential benefits of ATT as a
      new modality for stroke therapy, with other modalities.

PMID- 28758075
TI  - Stroke Impact Scale 3.0: Reliability and Validity Evaluation of the Korean
      Version.
AB  - OBJECTIVE: To establish the reliability and validity the Korean version of the
      Stroke Impact Scale (K-SIS) 3.0. METHODS: A total of 70 post-stroke patients were
      enrolled. All subjects were evaluated for general characteristics, Mini-Mental
      State Examination (MMSE), the National Institutes of Health Stroke Scale (NIHSS),
      Modified Barthel Index, Hospital Anxiety and Depression Scale (HADS). The SF-36
      and K-SIS 3.0 assessed their health-related quality of life. Statistical analysis
      after evaluation, determined the reliability and validity of the K-SIS 3.0.
      RESULTS: A total of 70 patients (mean age, 54.97 years) participated in this
      study. Internal consistency of the SIS 3.0 (Cronbach's alpha) was obtained, and
      all domains had good co-efficiency, with threshold above 0.70. Test-retest
      reliability of SIS 3.0 required correlation (Spearman's rho) of the same domain
      scores obtained on the first and second assessments. Results were above 0.5, with
      the exception of social participation and mobility. Concurrent validity of K-SIS
      3.0 was assessed using the SF-36, and other scales with the same or similar
      domains. Each domain of K-SIS 3.0 had a positive correlation with corresponding
      similar domain of SF-36 and other scales (HADS, MMSE, and NIHSS). CONCLUSION: The
      newly developed K-SIS 3.0 showed high inter-intra reliability and test-retest
      reliabilities, together with high concurrent validity with the original and
      various other scales, for patients with stroke. K-SIS 3.0 can therefore be used
      for stroke patients, to assess their health-related quality of life and treatment
      efficacy.

PMID- 28758076
TI  - Features of Golf-Related Shoulder Pain in Korean Amateur Golfers.
AB  - OBJECTIVE: To investigate the causes and characteristics of golf-related shoulder
      injuries in Korean amateur golfers. METHODS: Golf-related surveys were
      administered to, and ultrasonography were conducted on, 77 Korean amateur golfers
      with golf-related shoulder pain. The correlation between the golf-related surveys
      and ultrasonographic findings were investigated. RESULTS: The non-dominant
      shoulder is more likely to have golf-related pain and abnormal findings on
      ultrasonography than is the dominant shoulder. Supraspinatus muscle tear was the
      most frequent type of injury on ultrasonography, followed by subscapularis muscle
      tear. Investigation of the participants' golf-related habits revealed that only
      the amount of time spent practicing golf was correlated with supraspinatus muscle
      tear. No correlation was observed between the most painful swing phases and
      abnormal ultrasonographic findings. Participants who had not previously visited
      clinics were more likely to present with abnormal ultrasonographic findings, and
      many of the participants complained of additional upper limb pain. CONCLUSION:
      Golf-related shoulder injuries and pain are most likely to be observed in the non
      dominant shoulder. The supraspinatus muscle was the most susceptible muscle to
      damage. A correlation was observed between time spent practicing golf and
      supraspinatus muscle tear.

PMID- 28758077
TI  - Effects of Exercise on Neuropathy in Streptozotocin-Induced Diabetic Rats.
AB  - OBJECTIVE: To evaluate the effects of early regular exercise and to assess the
      electrophysiological and histopathological findings of the rat tail nerve in
      relation to the timing of exercise training for swimming exercise in rats with
      diabetic neuropathy. METHODS: We used 70 Sprague-Dawley male rats, and the
      experimental group comprised 60 rats, and the control group comprised 10 rats.
      Diabetes was induced by intraperitoneal injection of streptozotocin. Blood
      glucose concentrations were measured in tail vein blood samples. The experimental
      group was divided into 6 subgroups according to insulin treatment and swimming
      exercise: group 1, diabetic control; group 2, insulin treated; group 3, insulin
      untreated with early swimming exercise; group 4, insulin treated and early
      swimming exercise; group 5, insulin treated and late swimming exercise; and group
      6, insulin untreated with late swimming exercise. Sensory and motor nerve
      conduction studies were performed weekly up to the 13th week using rat tail
      nerves. The effect on structural diabetic neuropathy was assessed by morphometry
      and ultrastructural examination of the rat tail nerve fiber at the 14th week.
      RESULTS: An exercise effect was observed in the insulin treated groups, but it
      was not observed in the insulin untreated groups. The sensory nerve conduction
      study in the rat tail revealed significantly prolonged latency and decreased
      amplitude in groups 1 and 6, and a further delay was observed in group 5 when
      compared to group 4. Decreased thickness of myelin was found in groups 1 and 6
      through morphometry. CONCLUSION: Early regular exercise programs in addition to
      conventional insulin treatment may retard the progression of diabetic peripheral
      neuropathy.

PMID- 28758078
TI  - Contrast Spread in the Superoposterior Approach of Transforaminal Epidural
      Steroid Injections for Lumbosacral Radiculopathy.
AB  - OBJECTIVE: To observe the contrast spread in superoposterior transforaminal
      epidural steroid injection (SP TFESI) and investigate the correlation between
      spread patterns and efficacy. METHODS: Thirty-one patients with lumbosacral
      radiculopathy underwent single-level TFESI under fluoroscopy. The final needle
      tip position was targeted toward the SP quadrant of the intervertebral foramen.
      To observe the spread, 1 mL of contrast material was injected, followed by a
      steroid injection. The contrast spread was graded anteroposteriorly and
      vertically in the epidural space. The effect of SP TFESI was evaluated by
      proportional pain score reduction. RESULTS: Levels injected were L4-5 (n=20) and
      L5-S1 (n=11). Seventeen cases were lateral, and 14 were central herniated disc
      (HD). Baseline mean visual analog scale score was 6.23. Contrast dispersed
      dorsally in all the cases, and 45.2% cases showed a concurrent ventral spread.
      The proportion of the pain reduction after 2 weeks showed no difference between
      the two groups. In vertical spreading analysis, mean cephalic/caudal grades were
      1.40/1.55 at L4-5 level and 1.73/1.64 at L5-S1 level. The HD location had no
      effect on contrast dispersion. CONCLUSION: In SP TFESI, ventral contrast spread
      did not guarantee a better effect; however, the extent of cephalic flow in
      ventral expansion group correlated with the proportion of pain reduction.

PMID- 28758079
TI  - Ultrasonographic Study of the Anatomical Relationship Between the Lateral
      Antebrachial Cutaneous Nerve and the Cephalic Vein.
AB  - OBJECTIVE: To define the anatomy of the lateral antebrachial cutaneous nerve
      (LABCN) and the cephalic vein (CV) in the anterior forearm region of living
      humans using ultrasonography for preventing LABCN injury during cephalic
      venipuncture. METHODS: Thirty forearms of 15 healthy volunteers were evaluated
      using ultrasonography to identify the point where the LABCN begins to contact
      with the CV, and the point where the LABCN separates from the CV. The LABCN
      pathway in the forearm in relation to a nerve conduction study was also
      evaluated. RESULTS: The LABCNs came in contact with the CV at a mean of 0.6+/-1.6
      cm distal to the elbow crease, and separated from the CV at a mean of 7.0+/-3.4
      cm distal to the elbow crease. The mean distance between the conventionally used
      recording points (point R) for the LABCN conduction study and the actual
      sonographic measured LABCN was 2.4+/-2.4 mm. LABCN usually presented laterally at
      the point R (83.3%). CONCLUSION: The LABCN had close proximity to the CV in the
      proximal first quarter of the forearm. Cephalic venipuncture in this area should
      be avoided, and performed with caution if needed.

PMID- 28758080
TI  - Effects of Capping of the Tracheostomy Tube in Stroke Patients With Dysphagia.
AB  - OBJECTIVE: To investigate the impact of tracheostomy tube capping on swallowing
      physiology in stroke patients with dysphagia via videofluoroscopic swallowing
      study (VFSS). METHODS: This study was conducted as a prospective study that
      involved 30 stroke patients. Then, 4 mL semisolid swallowing was conducted with
      capping of the tracheostomy tube or without capping of the tracheostomy tube. The
      following five parameters were measured: laryngeal elevation, pharyngeal transit
      time, post-swallow pharyngeal remnant, upper esophageal sphincter width (UES),
      and penetration-aspiration scale (PAS) score. RESULTS: On assessment of the
      differences in swallowing parameters during swallowing between 'with capping' and
      'without capping' statuses, statistically significant differences were found in
      the post-swallow pharyngeal remnant (without capping, 48.19%+/-28.70%; with
      capping, 25.09%+/-19.23%; p<0.001), normalized residue ratio scale for the
      valleculae (without capping, 0.17+/-0.12; with capping, 0.09+/-0.12; p=0.013),
      normalized residue ratio scale for the piriform sinus (without capping, 0.16+/
      0.12; with capping, 0.10+/-0.07; p=0.015), and UES width (without capping, 3.32+/
      1.61 mm; with capping, 4.61+/-1.95 mm; p=0.003). However, there were no
      statistically significant differences in laryngeal elevation (x-axis without
      capping, 2.48+/-1.45 mm; with capping, 3.26+/-2.37 mm; y-axis without capping,
      11.11+/-5.24 mm; with capping, 12.64+/-6.16 mm), pharyngeal transit time (without
      capping, 9.19+/- 10.14 s; with capping, 9.09+/-10.21 s), and PAS score (without
      capping, 4.94+/-2.83; with capping, 4.18+/-2.24). CONCLUSION: Tracheostomy tube
      capping is a useful way to reduce post-swallow remnants and it can be considered
      an alternative method for alleviating dysphagia in stroke patients who can
      tolerate tracheostomy tube capping when post-swallow remnants are observed.

PMID- 28758081
TI  - Development of a Dysphagia Screening Test for Preterm Infants (DST-PI).
AB  - OBJECTIVE: To explore both the early prediction and diagnosis of dysphagia in
      preterm infants as an important developmental aspect as well as the prevention of
      respiratory complications, we developed the simple and-easy-to-apply Dysphagia
      Screening Test for Preterm Infants (DST-PI) to predict supraglottic penetration
      and subglottic aspiration. METHODS: Fifty-two infants were enrolled in a
      videofluoroscopic swallowing study (VFSS) due to clinical suspicions of
      dysphagia. Thirteen items related to supraglottic penetration or subglottic
      aspiration were initially selected from previous studies for the DST-PI. Finally,
      7 items were determined by linear logistic regression analysis. Cutoff values,
      sensitivity, specificity, and the area under the ROC curve (AUC) of the DST-PI
      for predicting supraglottic penetration or subglottic aspiration were calculated
      using a ROC curve. For inter-rater reliability, the kappa coefficient was
      calculated. RESULTS: Seven items were selected: 'gestational age,' 'history of
      apnea,' 'history of cyanosis during feeding,' 'swallowing pattern,' 'coughs
      during or after feeding,' 'decreased oxygen saturation within 3 minutes of
      feeding,' and 'voice change after feeding.' The Spearman correlation coefficient
      between the DST-PI and the penetration-aspiration scale (PAS) was 0.807
      (p<0.001). The sensitivity and specificity at different cutoff values for
      detecting supraglottic penetration and subglottic aspiration were 96.6% and 76.9%
      at 3.25, and 88.9% and 75.8% at 6.25, respectively. CONCLUSION: The DST-PI is a
      valid and reliable dysphagia screening test for supraglottic penetration or
      subglottic aspiration in preterm infants that is easy to apply in a clinical
      context.

PMID- 28758082
TI  - A New Instrument for Measuring Tibial Torsion in Pediatric Patients.
AB  - OBJECTIVE: To develop and test the validity and reliability of a new instrument
      for measuring the thigh-foot angle (TFA) for the patients with in-toeing and out
      toeing gait. METHODS: The new instrument (Thigh-Foot Supporter [TFS]) was
      developed by measuring the TFA during regular examination of the tibial torsional
      status. The study included 40 children who presented with in-toeing and out
      toeing gaits. We took a picture of each case to measure photographic-TFA (P-TFA)
      in the proper position and to establish a criterion. Study participants were
      examined by three independent physicians (A, B, and C) who had one, three and ten
      years of experience in the field, respectively. Each examiner conducted a
      separate classical physical examination (CPE) of every participant using a gait
      goniometer followed by a TFA assessment of each pediatric patient with or without
      the TFS. Thirty minutes later, repeated in the same way was measured. RESULTS:
      Less experienced examiner A showed significant differences between the TFA values
      depending on whether TFS used (left p=0.003 and right p=0.008). However,
      experienced examiners B and C did not show significant differences. Using TFS,
      less experienced examiner A showed a high validity and all examiner's inter-test
      and the inter-personal reliabilities increased. CONCLUSION: TFS may increase
      validity and reliability in measuring tibial torsion in patients who has a
      rotational problem in lower extremities. It would be more useful in less
      experienced examiners.

PMID- 28758083
TI  - Successful Extubation After Weaning Failure by Noninvasive Ventilation in
      Patients With Neuromuscular Disease: Case Series.
AB  - OBJECTIVE: To report successful cases of extubation from invasive mechanical
      ventilation at our institution using pulmonary rehabilitation consisting of
      noninvasive ventilation (NIV) in neuromuscular patients with experience of
      reintubation. METHODS: Patients who experienced extubation failure via the
      conventional weaning strategy but afterwards had extubation success via NIV were
      studied retrospectively. Continuous end-tidal CO2 (ETCO2) and pulse oxyhemoglobin
      saturation (SpO2) monitoring were performed. Extubation success was defined as a
      state not requiring invasive mechanical ventilation via endotracheal tube or
      tracheotomy during a period of at least 5 days. RESULTS: A total of 18 patients
      with ventilatory failure who initially experienced extubation failure were
      finally placed under part-time NIV after extubation. No patient had any serious
      or long-term adverse effect from NIV, and all patients left the hospital alive.
      CONCLUSION: NIV may promote successful weaning in neuromuscular patients with
      experience of reintubation.

PMID- 28758084
TI  - Cardiopulmonary Exercise Test in Leukemia Patients After Chemotherapy: A
      Feasibility Study.
AB  - OBJECTIVE: To explore the feasibility of cardiopulmonary exercise test (CPET) in
      leukemia patients after chemotherapy. METHODS: Leukemia patients with
      histologically confirmed hematologic malignancies were reviewed. We evaluated for
      CPET, between receiving chemotherapy and undergoing stem cell transplantation
      after 2 weeks. We recorded exercise testing and physiologic parameters during
      CPET between January 2013 to May 2015. All patients were subjected to symptoms
      limited to exercise testing, according to the Modified Bruce Protocol. We
      considered that if respiratory exchange ratio achieved was over 1.10,
      participants had successfully completed CPET. We dichotomized all participants
      into two groups (normal group, normal range of resting heart rate; higher group,
      over 100 per minute of heart rate). RESULTS: 30 patients were finally enrolled.
      All participants had no adverse effects during the exercise test. Mean peak
      double product was 26,998.60 mmHg.beats/min (range, 15,481-41,004), and mean peak
      oxygen consumption (VO2 peak) was 22.52+/-4.56 mL/kg/min. Significant differences
      were observed in the normal group with VO2 peak (mean, 24.21 mL/kg/min; p=0.027)
      and number of prior intensive chemotherapy, compared to the higher group (mean,
      1.95; p=0.006). CONCLUSION: Our results indicate that CPET in leukemia patients
      before stem cell transplantation was very safe, and is an efficient method to
      screen for patients with poor cardiac functions. As CPET presents the parameters
      which reveal the cardiopulmonary functions, including VO2 peak, double product
      and exercise capacity, this exercise test would help to predict the physical
      performance or general condition of the leukemia patients.

PMID- 28758085
TI  - Neuromuscular Electrical Stimulation and Strength Recovery of Postnatal Diastasis
      Recti Abdominis Muscles.
AB  - OBJECTIVE: To assess the effect of neuromuscular electrical stimulation (NMES) on
      the recovery of abdominal muscle strength in postnatal women with diastasis of
      recti abdominis muscles (DRAM). METHODS: Sixty women, 2 months postnatal,
      participated in this study. They were divided randomly into two equal groups.
      Group A received NMES in addition to abdominal exercises; group B received only
      abdominal exercises. The intervention in both groups was for three times per week
      for 8 weeks. The outcome measures were body mass index (BMI), waist/hip ratio,
      inter recti distance (IRD), and abdominal muscle strength in terms of peak
      torque, maximum repetition total work, and average power. RESULTS: Both groups
      showed highly significant (p<0.05) improvement in all outcomes. Further,
      intergroup comparisons showed significant improvement (p<0.05) in all parameters
      in favor of group A, except for the BMI. CONCLUSION: NMES helps reduce DRAM in
      postnatal women; if combined with abdominal exercises, it can augment the
      effects.

PMID- 28758086
TI  - Research Designs and Statistical Methods Trends in the Annals of Rehabilitation
      Medicine.
AB  - OBJECTIVE: To investigate trends of the research designs and statistical methods
      in the Annals of Rehabilitation Medicine (ARM) published from 2005 to 2015
      through a comparison of articles with the Archives of Physical Medicine and
      Rehabilitation (APMR). METHODS: The authors reviewed all articles published in
      ARM and APMR for the years 2005 and 2015 in order to determine their research
      designs as well as their statistical methods used in each article. RESULTS: In
      ARM, randomized controlled trials increased from 4.5% in 2005 to 6.5% in 2015. In
      APMR, randomized controlled trials increased from 8.1% in 2005 to 14.0% in 2015,
      meta-analyses increased to 5.3%, and systematic reviews increased to 6%. The
      number of studies using statistical methods increased in ARM from 1.9 to 2.6 per
      article and in APMR, from 2.7 to 3.1. Use of advanced methods in ARM also showed
      an increase from 2005 to 2015. CONCLUSION: This study concludes that there is a
      trend of increased awareness and attempts to use varied research approaches in
      ARM articles. There should also be more in-depth discussions and opportunities
      for researchers to share their experiences regarding statistical methods in the
      clinical field.

PMID- 28758087
TI  - Severe Ulnar Nerve Injury After Bee Venom Acupuncture at a Traditional Korean
      Medicine Clinic: A Case Report.
AB  - This case report describes a severe nerve injury to the right ulnar nerve, caused
      by bee venom acupuncture. A 52-year-old right-handed man received bee venom
      acupuncture on the medial side of his right elbow and forearm, at a Traditional
      Korean Medicine (TKM) clinic. Immediately after acupuncture, the patient
      experienced pain and swelling on the right elbow. There was further development
      of weakness of the right little finger, and sensory changes on the ulnar
      dermatome of the right hand. The patient visited our clinic 7 days after
      acupuncture. Electrodiagnostic studies 2 weeks after the acupuncture showed ulnar
      nerve damage. The patient underwent steroid pulse and rehabilitation treatments.
      However, his condition did not improve completely, even 4 months after
      acupuncture.

PMID- 28758088
TI  - Lipoma Compressing the Sciatic Nerve in a Patient With Suspicious Central Post
      stroke Pain.
AB  - Lipomas are mostly located in the subcutaneous tissues and rarely cause symptoms.
      Occasionally, peripheral nerve compression by lipomas is reported. We describe a
      case of a 59-year-old man with a left-middle cerebral artery infarction who was
      newly diagnosed as right basal ganglia and thalamic intracranial hemorrhage. He
      had neuropathic pain in the left arm and leg that was suspected to be central
      post-stroke pain. The administration of pain medication brought only temporary
      symptom relief. Nerve conduction and electromyography studies revealed left L5
      radiculopathy and he showed a positive 'sign of the buttock' in the left hip.
      Left-hip magnetic resonance imaging revealed an intermuscular lipoma compressing
      the sciatic nerve. After surgery, the range of motion in the left hip joint was
      significantly increased, and the patient's pain was relieved.

PMID- 28758089
TI  - Diagnosis of Churg-Strauss Syndrome Presented With Neuroendocrine Carcinoma: A
      Case Report.
AB  - Churg-Strauss syndrome (CSS) is a rare systemic vasculitis that affect small and
      medium-sized blood vessels and is accompanied by asthma, eosinophilia, and
      peripheral neuropathy. This report describes a case of a 52-year-old man who had
      a history of sinusitis, asthma, and thymus cancer and who had complained of
      bilateral lower extremity paresthesia and weakness for a month. Peripheral
      neuropathy was detected by electrodiagnostic studies. Resection of a mediastinal
      mass, which was diagnosed as thymic neuroendocrine carcinoma, was performed five
      months before his visit. After thymectomy, peripheral blood tests revealed a
      gradual increase in eosinophils. Two months after surgery, he was admitted to the
      hospital for dyspnea, and nodules of focal consolidation were found in his chest
      X-ray. One month later, pyoderma occurred in the right shin, and the skin biopsy
      showed extravascular eosinophilic infiltration. He was diagnosed with CSS after
      thymectomy, and we report a very rare case of CSS presented with thymic
      neuroendocrine carcinoma.

PMID- 28758090
TI  - Intramuscular Hematoma Following Radial Extracorporeal Shockwave Therapy for
      Chronic Neurogenic Heterotopic Ossification: A Case Report.
AB  - Extracorporeal shockwave therapy (ESWT) has been reported to be a safe and
      effective method for decreasing pain and relieving range of motion (ROM)
      limitations caused by neurogenic heterotopic ossification (NHO), though there has
      been no report that it might cause hematoma if applied to NHO. We hereby report a
      case of massive hematoma after ESWT, specifically the radial shockwave therapy
      (RSWT) device at both hips in a 49-year-old female patient with NHO. She had
      developed NHO after extensive subarachnoid hemorrhage. We had applied RSWT
      according to the previous report. The pain and the ROM limitations were gradually
      improved. Six weeks later, she reported pain and ROM limitations on the right
      hip. From a medial aspect, swelling and bruising of the right thigh could be
      seen. Magnetic resonance imaging and ultrasonography suggested a large hematoma
      between right hip adductor muscles. The symptoms disappeared after conservative
      treatment for one month, and subsequent follow-up imaging studies demonstrated
      resolution of the hematoma.

PMID- 28758091
TI  - Identifying the KAT6B Mutation via Diagnostic Exome Sequencing to Diagnose Say
      Barber-Biesecker-Young-Simpson Syndrome in Three Generations of a Family.
AB  - Diagnostic exome sequencing (DES) is a powerful tool to analyze the pathogenic
      variants leading to development delay (DD) and intellectual disability (ID).
      Recently, heterozygous de novo mutation of the histone acetyltransferase encoding
      gene KAT6B has been recognized as causing a syndrome with congenital anomalies
      and intellectual disability, namely Say-Barber-Biesecker-Young-Simpson (SBBYS)
      syndrome. Here we report a case of SBBYS syndrome in a third generation Korean
      family affected with a missense mutation in KAT6B, c.2292C>T p.(His767Tyr)
      identified by DES. This is the first confirmed familial inherited mutation of the
      KAT6B reported worldwide. Our case emphasizes again the importance of basic
      physical examination and taking a family history. Furthermore, advances in
      genetic diagnostic tools are becoming key to identifying the etiology of DD and
      ID. This allows a physiatrist to predict the disease's clinical evolution with
      relative certainty, and offer an appropriate rehabilitation plan for patients.

PMID- 28758092
TI  - A Case of Grisel Syndrome Showing No Underlying Laxity of the Atlanto-axial
      Joint.
AB  - Grisel syndrome is a rare, non-traumatic atlanto-axial subluxation associated
      with an inflammatory or infectious process in the upper neck. According to the
      two-hit hypothesis, which is widely accepted for the pathogenesis of Grisel
      syndrome, preexisting ligamentous laxity of the atlanto-axial joint is regarded
      as the first hit. An inflammatory or infectious process of the atlanto-axial
      joint acts as the second hit, resulting in non-traumatic atlanto-axial
      subluxation. We report on a 6-year-old girl with atlanto-axial subluxation
      following retropharyngeal and cervical lymphadenitis. She was diagnosed with
      Grisel syndrome, for which an initial computed tomography did not show any
      preexisting ligamentous laxity of the atlanto-axial joint. A literature review
      found only 4 case reports on Grisel syndrome with an initially normal atlanto
      axial joint. The present case offers some evidence that a single hit, such as
      inflammatory changes in the atlanto-axial joint, might cause Grisel syndrome,
      even without underlying ligamentous laxity.

PMID- 28758094
TI  - Cancer diagnostics: current concepts and future perspectives.

PMID- 28758093
TI  - Effect of Interactions between Harvester Ants on Forager Decisions.
AB  - Harvester ant colonies adjust their foraging activity to day-to-day changes in
      food availability and hour-to-hour changes in environmental conditions. This
      collective behavior is regulated through interactions, in the form of brief
      antennal contacts, between outgoing foragers and returning foragers with food.
      Here we consider how an ant, waiting in the entrance chamber just inside the nest
      entrance, uses its accumulated experience of interactions to decide whether to
      leave the nest to forage. Using videos of field observations, we tracked the
      interactions and foraging decisions of ants in the entrance chamber. Outgoing
      foragers tended to interact with returning foragers at higher rates than ants
      that returned to the deeper nest and did not forage. To provide a mechanistic
      framework for interpreting these results, we develop a decision model in which
      ants make decisions based upon a noisy accumulation of individual contacts with
      returning foragers. The model can reproduce core trends and realistic
      distributions for individual ant interaction statistics, and suggests possible
      mechanisms by which foraging activity may be regulated at an individual ant
      level.

PMID- 28758095
TI  - Clinical presentation and epidemiology of brain tumors firstly diagnosed in
      adults in the Emergency Department: a 10-year, single center retrospective study.
AB  - BACKGROUND: Several patients with new onset brain tumors present to the Emergency
      Department (ED) complaining for new symptoms. Although information exists on
      symptom prevalence in the entire population of patients with brain tumors, little
      is known about the clinical presentation in ED. This retrospective study was
      planned to investigate clinical presentation and epidemiology of brain tumors
      firstly diagnosed in a large urban ED throughout a 10-year period. METHODS: All
      medical records of patients aged >=18 years, discharged from our ED with a
      diagnosis of brain tumor were retrieved from the electronic hospital database
      during a 10-year period (2006 to 2015). The records were reassessed for selecting
      only brain tumors firstly diagnosed in the ED. The symptoms at presentation were
      divided in six categories: (I) headache; (II) seizures; (III) focal signs; (IV)
      altered mental status; (V) nausea/vomiting/dizziness; (VI) trauma. For all cases,
      the hospital record was retrieved, to obtain histologic classification of tumors.
      Patients with inflammatory neoformations were excluded from the study. RESULTS:
      Overall, 205 patients with firstly diagnosed brain tumor were identified among
      870,135 ED visits (i.e., <1%). Glial tumors were the most frequent (50% of the
      entire sample). No significant differences were found between mean age of
      patients in the different histologically based groups (meningiomas 66+/-14;
      glioblastomas 65+/-16 years; metastases 66+/-13 years; other miscellaneous 66+/
      19 years). Focal signs accounted for more than 50% of all presentation
      signs/symptoms. CONCLUSIONS: First presentation of brain tumor in the ED is not a
      rare occurrence, so that the emergency physicians should be aware of this
      possibility.

PMID- 28758097
TI  - Prognostic value of red blood cell distribution width in hepatocellular
      carcinoma.
AB  - Red blood cell distribution width (RDW) is a simple, inexpensive, routinely
      measured and automatically reported blood test parameter, which reflects the
      degree of anisocytosis of red blood cells in peripheral blood. RDW was found to
      be associated with and retain clinical significance for assessing disease
      severity and outcomes in a number of hematological and solid malignancies. Motley
      of interacting clinical and biochemical factors have an impact on the red cell
      population biology. Malignancies per se can act as a causative factor, or
      anisocytosis may develop as a result of chronic inflammation. RDW has also been
      shown to be affected by nutritional status, which is typically deranged in
      malignancies. RDW is shown to be a clinically useful marker of disease severity
      and level of fibrosis in liver cirrhosis of various causes such as hepatitis B,
      hepatitis C and non-alcoholic fatty liver disease. Whether liver cirrhosis
      patients with higher RDW are at increased risk of hepatocellular cancer is yet to
      be determined, but several lines of evidence confirm that RDW has clinical
      significance in hepatocellular carcinoma (HCC). In this review, we specifically
      discuss the current literature about the association between RDW and HCC. The
      available evidences were summarized and the potential underlying mechanisms were
      analyzed.

PMID- 28758096
TI  - Type 2 diabetes mellitus and risk of hepatocellular carcinoma: spotlight on
      nonalcoholic fatty liver disease.
AB  - The incidence of both type 2 diabetes mellitus (T2DM) and multiple cancer types
      are rapidly increasing worldwide. Several studies documented that T2DM is closely
      associated with an increased incidence of cancer. However, while some
      methodological considerations preclude a definitive association between T2DM and
      the risk of certain cancers, the relationship between T2DM and increased risk of
      incident hepatocellular carcinoma (HCC) remains significant even after adjustment
      for detection bias and reverse causation, indicating that such association is
      clinically reliable and robust. In addition, a number of observational studies
      also showed that T2DM is associated with higher mortality among persons with HCC.
      Some recent meta-analyses suggested that treatment with metformin may be
      associated with a lower risk of HCC, and may also beneficially influence HCC
      prognosis, whereas treatment with sulphonylureas or insulin seems to be related
      to a higher HCC risk. The underlying biological mechanisms linking T2DM and HCC
      are complex and difficult to elucidate, but the existence of close inter
      connections among T2DM, obesity and nonalcoholic fatty liver disease (NAFLD)
      induces hepatic/systemic insulin resistance and causes the release of multiple
      pro-inflammatory cytokines, vasoactive factors and pro-oxidant molecules, which
      are all potentially implicated in the development and progression of HCC. In this
      clinical review, we discuss the epidemiological evidence linking T2DM to the risk
      of HCC. Moreover, we also briefly discuss the putative underlying mechanisms
      linking T2DM, NAFLD and HCC, and the potential effect of certain hypoglycemic
      agents on the risk of developing HCC.

PMID- 28758098
TI  - Mobile phone radiofrequency exposure has no effect on DNA double strand breaks
      (DSB) in human lymphocytes.
AB  - BACKGROUND: The use of mobile phones has been associated with an increased risk
      of developing certain type of cancer, especially in long term users. Therefore,
      this study was aimed to investigate the potential genotoxic effect of mobile
      phone radiofrequency exposure on human peripheral blood mononuclear cells in
      vitro. METHODS: The study population consisted in 14 healthy volunteers. After
      collection of two whole blood samples, the former was placed in a plastic rack, 1
      cm from the chassis of a commercial mobile phone (900 MHz carrier frequency),
      which was activated by a 30-min call. The second blood sample was instead
      maintained far from mobile phones or other RF sources. The influence of mobile
      phone RF on DNA integrity was assessed by analyzing gamma-H2AX foci in
      lymphocytes using immunofluorescence staining kit on AKLIDES. RESULTS: No measure
      of gamma-H2AX foci was significantly influenced by mobile phone RF exposure, nor
      mobile phone exposure was associated with significant risk of genetic damages in
      vitro (odds ratio comprised between 0.27 and 1.00). CONCLUSIONS: The results of
      this experimental study demonstrate that exposure of human lymphocytes to a
      conventional 900 MHz RF emitted by a commercial mobile phone for 30 min does not
      significantly impact DNA integrity.

PMID- 28758099
TI  - Platelet expression of PKCepsilon oncoprotein in myelofibrosis is associated with
      disease severity and thrombotic risk.
AB  - BACKGROUND: Myelofibrosis (MF) is the most aggressive Philadelphia-negative
      chronic myeloproliferative neoplasm (MPN) with high morbidity and mortality due
      to thrombo-hemorrhagic complications and leukemic transformation. MF is
      characterized by profound alterations of megakaryocytopoiesis, with consequent
      abnormalities in platelet number and function. We recently showed that the
      overexpression of the oncoprotein PKCepsilon plays a key role in the aberrant
      differentiation of MF megakaryocyte clone and that its levels correlate with
      disease burden. Moreover, our group previously demonstrated that PKCepsilon is
      over-expressed in platelets from patients with acute myocardial infarction (MI)
      and accounts for their increased reactivity. On these bases, we investigated here
      the activation state and PKCepsilon expression of MF platelets, testing potential
      correlations with thrombotic risk and disease aggressiveness. METHODS: Platelets
      were isolated from peripheral blood samples of MF patients and healthy donors
      (HDs). Patients were stratified according to the IPSS/DIPSS risk category and
      history of cardiovascular events. Platelet activation was assessed by flow
      cytometry. PKCepsilon mRNA and protein levels were determined by real time-PCR
      and western blot. RESULTS: MF platelets circulate in an activated status and
      display significantly higher levels of PKCepsilon compared to HDs. In MF
      patients, PKCepsilon platelet levels were associated with high-risk disease as
      well as with a positive history of major cardiovascular events. CONCLUSIONS:
      PKCepsilon is configuring as the common denominator of neoplastic transformation
      and thrombus formation in MF. Overall, our data pinpoint PKCepsilon as a
      potential novel biomarker of disease aggressiveness and thrombotic risk in this
      hematologic neoplasm.

PMID- 28758100
TI  - Appropriateness of tumor marker request: a case of study.
AB  - Appropriateness is crucial to provide efficient and high-quality health services
      at affordable costs. Laboratory medicine is a sector of special interest for the
      investigation of inappropriateness, due to the high rate of technological
      innovation and its pivotal role in many diseases and clinical settings. Some
      subjective aspects related to either the patient or physician seem to have a
      major role on inappropriateness rates. Given the psychological impact of cancer
      on both patients and physicians, tumor markers represent a case of study for
      appropriateness. The assessment of inappropriateness of laboratory tests has been
      focused mainly on ordering patterns. Appropriateness can barely be appraised by
      matching the requested test with the clinical problem because clinical
      information on the test requisition form is usually inadequate. Monitoring
      inappropriateness through individual clinical information may be feasible in
      inpatient (clinical data are available), while an indirect approach should be
      used for outpatients. To estimate inappropriateness in outpatients our group
      developed innovative models based on comparison between the actually ordered and
      expected requests of tumor marker, calculated according to recommendations of
      clinical practice guidelines (CPGs) applied to figures of cancer prevalence. The
      implementation of the model at national scale in Italy led to recognize a very
      high rate of overordering of tumor markers. The model was further focused by a
      dedicated algorithm to be adapted to different clinical conditions or
      organizational settings by applying performance indicators to cohort-wide
      structured information in electronic health records (EHRs). With this novel
      approach, we showed that inappropriateness is multifaceted even within the
      specific category of tumour markers. The model was effective in identifying both
      over- and underordering. Implementation of evidence based information and
      monitoring their impact on the clinical practice are parts of the same,
      multistage, process aimed at the progressive improvement of health care.

PMID- 28758101
TI  - BRCA population screening for predicting breast cancer: for or against?
AB  - The pathogenesis of breast cancer, the most frequent female malignancy, entails
      both genetic and acquired risk factors. Among the various oncogenetic mutations,
      those involving the BReast Cancer 1 (BRCA1) and BReast Cancer 2 (BRCA2) genes are
      associated with an extremely high risk of developing breast cancer, with a
      penetration approximating 70% in women with a positive family history for this
      malignancy. This important evidence elicits some pragmatic considerations, such
      as the clinical effectiveness of screening for the most penetrant BRCA mutations
      in women with or without a positive familial history, but also raises important
      issues related to the most appropriate clinical management of these patients.
      Despite it seems now almost certain that BRCA testing should be offered to women
      with a positive familial history for breast cancer, the balance between
      advantages and limitations of a population screening remains largely debated.
      Whatever conclusion can be reach at this point in time must be accurately weighed
      against at least four different perspectives, which include the low prevalence of
      these mutations in the general population, the relatively lower risk of
      developing breast cancer in women without a familial history for this malignancy,
      the direct and indirect cost of genetic testing and, last but not least, the many
      potential psychological and clinical consequences in patients receiving a
      positive test result. Many of these still unresolved issues will be tentatively
      discussed in this article.

PMID- 28758103
TI  - Circulating microRNAs as emerging non-invasive biomarkers for gliomas.
AB  - No single circulating biomarker has been put to practice for malignant gliomas so
      far, the most lethal primary brain tumors. Many promising protein biomarkers such
      as the mutant EGFRvIII or glial fibrillary acidic protein (GFAP) have already
      been detected in the blood and cerebrospinal fluid (CSF) of patients with
      gliomas, but their clinical value is still pending validation. Furthermore, these
      and other proteins seem to lack sufficient sensitivity and specificity required
      for a successful biomarker in this clinical setting. The expression profiling of
      microRNAs (miRNAs) has already entered cancer clinics as diagnostic and
      prognostic biomarkers, for assessing tumor initiation, progression and response
      to treatment. Large-scale miRNA expression analyses reported both up-regulation
      and down-regulation of several miRNAs in tumour tissues from patients with
      gliomas compared to normal brain tissue, thus supporting the development of miRNA
      based biomarkers. Using comprehensive high-throughput approaches, such as
      microarrays, different circulating miRNAs were proposed as potential biomarkers
      of gliomas. This review is aimed to summarize the clinical evidence about
      circulating miRNA biomarkers discovered to date. Mandatory issues to develop
      clinically validated biomarkers to improve time of diagnosis, predicting response
      to treatment and prognosis of patients with gliomas are also herein addresses.

PMID- 28758102
TI  - Circulating biomarkers in epithelial ovarian cancer diagnosis: from present to
      future perspective.
AB  - Ovarian cancer (OC) represents the most lethal gynecological cancer and the poor
      prognosis is often attributable to late diagnosis. The diagnostic approach to
      woman presenting with pelvic mass is difficult and differential diagnosis often
      requires invasive histological examination. Serum CA125 and HE4, as well as the
      most of the other serum biomarkers discovered and validated, are not sufficiently
      sensitive and specific to make early diagnosis. Moreover, conflicting results
      exist about the improvement of diagnostic performance by using multivariate index
      assays, developed by combining circulating biomarkers with other variables (i.e.,
      ultrasound and/or menopausal status and/or age), in comparison to CA125 or HE4
      alone. In the last years, several studies focused on the microRNAs (miRs), short
      single-stranded non-coding RNA that regulate several messenger RNAs (mRNAs). As
      in other cancer types, the aberrant miRs expression has been demonstrated in
      gynecological cancers, in both tissues and serum samples. In particular, the
      diagnostic performance of single or miRs panels resulted very high. However, to
      date, despite the potential clinical utility has been demonstrated, none of these
      miRs has been validated in large OC populations.

PMID- 28758104
TI  - Liquid biopsies in lung cancer-time to implement research technologies in routine
      care?
AB  - Lung cancer is the leading cause of cancer mortality. A substantial progress in
      the understanding of lung cancer biology has resulted in several promising
      targeted therapies for advanced disease. Druggable targets today include point
      mutations such as EGFR, BRAF and re-arrangements in genes such as ALK and ROS1.
      Liquid biopsies collecting e.g., circulating tumor DNA (ctDNA) reflects overall
      tumor information and is not biased by analyzing of only a small fraction of the
      tumor and is always accessible in contrast to the lung cancer tissue.
      Technological advances in detection of low frequency mutation variants in ctDNA
      have made it the dominating liquid biopsy platform in terms of utility and
      sensitivity. Circulating DNA or RNA may possible be used to define populations
      with higher risk of developing lung cancer, thus reducing screening cohorts and
      increasing the positive predictive value of screening. Blood based-tests may also
      aid to identify genetic alterations several weeks prior to radiologically
      verified recurrence and may be of great value in the follow-up of lung cancer
      patients. Besides being an alternative to invasive biopsies in selected cases,
      liquid biopsies offer a unique possibility to monitor treatment response
      following medical treatment as well as treatment response and resistance
      development after targeted therapy, giving a possibility to modify the treatment
      after the genetic profile of the tumor. Ideally, genetic alterations found in
      ctDNA could be tracked in real-time discriminating between fast-growing life
      threatening tumors from more indolent slow growing tumors or premalignant growth
      that are of no concern for the wellbeing of the patient. This review focuses on
      future perspectives of liquid biopsies in lung cancer care for different clinical
      settings and present current technological platforms for further discussion of
      possible strategies for implementation of liquid biopsies in lung cancer.

PMID- 28758105
TI  - Epigenetics of colorectal cancer: emerging circulating diagnostic and prognostic
      biomarkers.
AB  - Colorectal cancer (CRC) is one of the most common cancers worldwide and the
      second leading cause of cancer-related mortality in western countries. Despite
      the high incidence, treatment options for advanced CRC remain limited and
      unsuccessful, resulting in a poor prognosis. Therefore, novel accurate
      diagnostic, prognostic and predictive biomarkers are clearly and urgently needed
      to detect advanced colon polyps and early stage CRC and to identify the most
      effective treatments for specific CRC patients. CRC is known to develop from
      early premalignant lesions to full blown cancer via a multi-step process
      involving a series of genetic mutations that accumulate over time. Recent
      improvement of our understanding of CRC biology and advances in genomic
      technologies has led to the identification of a variety of epigenetic alterations
      strongly involved in cancer initiation and progression. Among the epigenetic
      marks implicated in CRC the most widely studied are the global DNA
      hypomethylation, the promoter hypermethylation and the miRNAs dysregulations.
      Many evidence exist that such tumour associated alterations may serve as new
      potential biomarkers. Moreover, due the non-invasive, objective, and potential
      reproducible assessment, circulating epigenetic biomarkers have reached
      increasing attentions in the last few years. In this review, we attempt to
      analyze the existing most recent literature on the role of circulating DNA
      methylations and miRNAs alterations in CRC diagnosis and prognosis.

PMID- 28758106
TI  - Neopterin as a biomarker of immune response in cancer patients.
AB  - With the advent of immunotherapy the topic of biomarkers of immune response is of
      high interest. Along with the expression of programmed death ligand 1 (PD-L1) or
      tumor infiltrating lymphocytes (TIL), biomarkers of macrophage activation could
      be of interest. Neopterin is a biomarker of immune activation increased in
      different disorders associated with immune activation, including cancer.
      Neopterin synthesis is induced by interferon-gamma that also induces indoleamine
      2,3-dioxygenase (IDO), an enzyme catalyzing catabolism of tryptophan to
      kynurenine. Increased urinary or serum concentrations of neopterin have been
      associated with poor prognosis across a spectrum of malignant disorders of
      different primary location. Neopterin concentration in peripheral blood as well
      as in the tumor microenvironment correlates with phenotypic and functional
      changes of lymphocytes, indicating immune dysfunction. Increased neopterin
      concentrations are also accompanied by increased rate of conversion of tryptophan
      to kynurenine. Increasing neopterin concentrations also accompany side effects of
      anticancer treatment and could predict subsequent complications. Although almost
      four decades have elapsed since the discovery of increased neopterin
      concentrations in cancer patients, the full potential of neopterin as a biomarker
      in this setting has not been so far realized.

PMID- 28758108
TI  - Blood Transcriptional Signatures for Disease Progression in a Rat Model of
      Osteoarthritis.
AB  - Biomarkers of osteoarthritis (OA) that can accurately diagnose the disease at the
      earliest stage would significantly support efforts to develop treatments for
      prevention and early intervention. We have sought to determine the time course of
      alterations in peripheral blood gene expression profile associated with the
      development of OA. Blood samples were collected from a tail vein of individual
      rats with monosodium iodoacetate- (MIA-) induced OA (2, 14, 21, and 28 days after
      the treatment). We used whole-genome microarrays to reveal OA-related
      transcriptional alterations of 72 transcripts. Three main groups of coexpressed
      genes revealed diverse time-dependent profiles of up- and downregulation.
      Functional links that connect expression of the gradually downregulated genes to
      the G13 signaling pathway were indicated. The mRNA abundance levels of the
      identified transcripts were further analyzed in publicly available gene
      expression dataset obtained from a GARP study cohort of OA patients. We revealed
      three-gene signature differentially expressed in both rat and human blood (TNK2,
      KCTD2, and WDR37). The alterations in expression of the selected transcripts in
      peripheral blood samples of the patients indicate heterogeneity of the OA
      profiles potentially related to disease progress and severity of clinical
      symptoms. Our study identifies several potential stage-specific biomarkers of OA
      progression.

PMID- 28758107
TI  - Ganoderma spp.: A Promising Adjuvant Treatment for Breast Cancer.
AB  - For the past several decades, cancer patients in the U.S. have chosen the use of
      natural products as an alternative or complimentary medicine approach to treat or
      improve their quality of life via reduction or prevention of the side effects
      during or after cancer treatment. The genus Ganoderma includes about 80 species
      of mushrooms, of which several have been used for centuries in traditional Asian
      medicine for their medicinal properties, including anticancer and
      immunoregulatory effects. Numerous bioactive compounds seem to be responsible for
      their healing effects. Among the approximately 400 compounds produced by
      Ganoderma spp., triterpenes, peptidoglycans and polysaccharides are the major
      physiologically-active constituents. Ganoderma anticancer effects are attributed
      to its efficacy in reducing cancer cell survival and growth, as well as by its
      chemosensitizing role. In vitro and in vivo studies have been conducted in
      various cancer cells and animal models; however, in this review, we focus on
      Ganoderma's efficacy on breast cancers. Evidence shows that some species of
      Ganoderma have great potential as a natural therapeutic for breast cancer.
      Nevertheless, further studies are needed to investigate their potential in the
      clinical setting and to translate our basic scientific findings into therapeutic
      interventions for cancer patients.

PMID- 28758109
TI  - Dissemination and Molecular Characterization of Staphylococcus aureus at a
      Tertiary Referral Hospital in Xiamen City, China.
AB  - Staphylococcus aureus is a global epidemic pathogen that causes heavy disease
      burden. The aim of this study was to determine which globally known S. aureus
      lineages are currently present in a hospital of Xiamen. Therefore, the 426 S.
      aureus strains were detected by Melting Curve Analysis (MCA) and genotyped by
      Pulsed Field Gel Electrophoresis (PFGE) as well as Multicolor Melting Curve
      Analysis-Based Multilocus Melt Typing (MLMT). In addition, Multilocus Sequence
      Typing (MLST) was used to identify 108 representative strains. In light of
      eighteen antibiotics except for Vancomycin (by Broth Dilution Method), we used
      the Kirby-Bauer disc diffusion method to assess antibiotic susceptibility of 426
      S. aureus strains. Finally, PFGE analysis revealed 14 different patterns with
      three major patterns (C10, C8, and C11) that accounted for 69.42% of all S.
      aureus strains, and MT-1~MT-5 occupied most part of the strains by MLMT. MLST
      revealed 25 different STs with the predominant types being ST239, ST59, and
      ST188. There have been 8 antibiotics that showed more than 50% resistance of all
      S. aureus strains. In summary, we found several of the lineages are predominant
      in our hospital. And antibiotic resistance is still a severe problem that needs
      to be controlled in clinic.

PMID- 28758110
TI  - Comparisons of Efficacy of Intravitreal Aflibercept and Ranibizumab in Eyes with
      Diabetic Macular Edema.
AB  - We compared the efficacy of intravitreal aflibercept (IVA) to intravitreal
      ranibizumab (IVR) injections in eyes with diabetic macular edema (DME). The
      medical records of 49 eyes of 36 patients who were diagnosed with DME and had
      received IVR and 46 eyes of 40 patients who had received IVA treatment were
      reviewed. The central macular thickness (CMT) and best-corrected visual acuity
      (BCVA) were measured at the baseline and at 1, 3, and 6 months after the IVR or
      IVA. The mean number of injections of IVR was 2.6 +/- 1.1 and of IVA was 2.7 +/-
      1.4. At 6 months, the CMT was significantly thinner than the baseline after IVR
      and after IVA. The mean BCVA was significantly better than the baseline after IVR
      only at 1 and 3 months and after IVA at 1 and 6 months. The BCVA of eyes with
      serous retinal detachment (SRD) was significantly better at 1 month after the IVR
      and at 1 month and 6 months after the IVA. The BCVAs improved more significantly
      in the SRD+ group than in the SRD- group. The effects of IVA persist longer than
      that of IVR. The effectiveness of both IVR and IVA was not dependent on the
      presence of SRD (IRB#2107).

PMID- 28758111
TI  - The Neuroprotective Effects of Muscle-Derived Stem Cells via Brain-Derived
      Neurotrophic Factor in Spinal Cord Injury Model.
AB  - Muscle-derived stem cells (MDSCs) possess multipotent differentiation and self
      renewal capacities; however, the effects and mechanism in neuron injury remain
      unclear. The aim of this study was to investigate the effects of MDSCs on neuron
      secondary injury, oxidative stress-induced apoptosis. An in vivo study showed the
      Basso, Beattie, and Bresnahan (BBB) score and number of neurons significantly
      increased after MDSCs' transplantation in spinal cord injury (SCI) rats. An in
      vitro study demonstrated that MDSCs attenuated neuron apoptosis, and the
      expression of antioxidants was upregulated as well as the ratio of Bcl-2 and Bax
      in the MNT (MDSCs cocultured with injured neurons) group compared with the NT
      (injured neurons) group. Both LC3II/LC3I and beta-catenin were enhanced in the
      MNT group, while XAV939 (a beta-catenin inhibitor) decreased the expression of
      nuclear erythroid-related factor 2 (Nrf2) and LC3II/LC3I. Moreover, MDSCs became
      NSE- (neuron-specific enolase-) positive neuron-like cells with brain-derived
      neurotrophic factor (BDNF) treatment. The correlation analysis indicated that
      there was a significant relation between the level of BDNF and neuron injury.
      These findings suggest that MDSCs may protect the spinal cord from injury by
      inhibiting apoptosis and replacing injured neurons, and the increased BDNF and
      beta-catenin could contribute to MDSCs' effects.

PMID- 28758112
TI  - Parental Genetic Variants, MTHFR 677C>T and MTRR 66A>G, Associated Differently
      with Fetal Congenital Heart Defect.
AB  - BACKGROUND: Congenital heart defect (CHD) is one of the most common birth defects
      in the world. The methylenetetrahydrofolate reductase (MTHFR) and methionine
      synthase reductase (MTRR) genes are two of the most important candidate genes for
      fetal CHD. However, the correlations between the two genes and fetal CHD were
      inconsistent in various reports. Therefore, this study is aimed to evaluate the
      parental effects of the two genes on fetal CHD via three genetic polymorphisms,
      MTHFR 677C>T (rs1801133), MTHFR 1298 A>C (rs1801131), and MTRR 66A>G (rs1801394).
      METHODS: Parents with pregnancy history of fetal CHD were divided into two
      subgroups: ventricular septal defect (VSD) (21) and non-VSD groups (78). VSD, non
      VSD, and 114 control parents (controls) were analyzed in this study. Genotyping
      of these genetic polymorphisms was done by sequencing. RESULTS: The MTHFR 677C>T
      polymorphism of either mothers or fathers was independently associated with fetal
      non-VSD (P < 0.05) but not VSD, while the MTRR 66A>G polymorphism was
      independently associated with fetal VSD (P < 0.05) but not non-VSD. No
      significance was found for MTHFR 1298A>C polymorphism. CONCLUSION: In either
      maternal or paternal group, the MTHFR 677C>T polymorphism was independently
      related to fetal non-VSD, while the MTRR 66A>G polymorphism was independently
      related to fetal VSD.

PMID- 28758113
TI  - Real World Evidence: A Quantitative and Qualitative Glance at Participant
      Feedback from a Free-Response Survey Investigating Experiences of a Structured
      Exercise Intervention for Men with Prostate Cancer.
AB  - AIM: To explore patient experiences of a structured exercise intervention for men
      with prostate cancer (PCa). SAMPLE: 41 men with either localised or advanced PCa
      who had been referred for a structured exercise programme by their physician and
      then subsequently consented to a telephone survey. METHOD: Participants underwent
      a 10-week supervised exercise programme within a large cancer centre hospital
      consisting of 8 sessions. They then completed a short multiple choice telephone
      survey, elaborating on their responses where appropriate. Views expressed by
      participants were analysed using an affinity diagram and common themes were
      identified. RESULTS: Feedback from our telephone surveys was consistently
      positive and suggests that the structured exercise intervention provides exercise
      confidence, motivation to exercise, and social support and promotes positive
      health behaviour change in the context of exercise. Individual differences arose
      amongst participants in their perceived utility of the intervention, with 73.3%
      expressing a preference for structured exercise classes and 19.5% expressing a
      preference for exercising independently. CONCLUSION: Design of a structured
      exercise intervention for patients with PCa should embrace the positive aspects
      outlined here but consider patients' individual differences. Ongoing feedback
      from patients should be utilised alongside traditional study designs to inform
      intervention design in this area.

PMID- 28758115
TI  - Corrigendum to "Assessment of Hip Fracture Risk Using Cross-Section Strain Energy
      Determined by QCT-Based Finite Element Modeling".
AB  - [This corrects the article DOI: 10.1155/2015/413839.].

PMID- 28758114
TI  - Immunotherapy in Gastrointestinal Cancers.
AB  - Gastrointestinal cancers represent a major public health problem worldwide.
      Immunotherapeutic strategies are currently under investigation in this setting
      and preliminary results of ongoing trials adopting checkpoint inhibitors are
      striking. Indeed, although a poor immunogenicity for GI has been reported, a
      strong biological rationale supports the development of immunotherapy in this
      field. The clinical and translational research on immunotherapy for the treatment
      of GI cancers started firstly with the identification of immune-related
      mechanisms possibly relevant to GI tumours and secondly with the development of
      immunotherapy-based agents in clinical trials. In the present review a general
      overview is firstly provided followed by a focus on major findings on gastric,
      colorectal, and hepatocellular carcinomas. Finally, pathological and molecular
      perspectives are provided since many efforts are ongoing in order to identify
      possible predictive biomarkers and to improve patients' selection. Many issues
      are still unsolved in this field; however, we strongly believe that immunotherapy
      might positively affect the natural history of a subgroup of GI cancer patients
      improving outcome and the overall quality of life.

PMID- 28758116
TI  - Structure and Function of Trypsin-Loaded Fibrinolytic Liposomes.
AB  - Protease encapsulation and its targeted release in thrombi may contribute to the
      reduction of haemorrhagic complications of thrombolysis. We aimed to prepare
      sterically stabilized trypsin-loaded liposomes (SSLT) and characterize their
      structure and fibrinolytic efficiency. Hydrogenated soybean phosphatidylcholine
      based SSLT were prepared and their structure was studied by transmission electron
      microscopy combined with freeze fracture (FF-TEM), Fourier transform infrared
      spectroscopy (FT-IR), and small-angle X-ray scattering (SAXS). Fibrinolytic
      activity was examined at 45, 37, or 24 degrees C on fibrin or plasma clots with
      turbidimetric and permeation-driven lysis assays. Trypsin was shown to be
      attached to the inner surface of vesicles (SAXS and FF-TEM) close to the lipid
      hydrophilic/hydrophobic interface (FT-IR). The thermosensitivity of SSLT was
      evidenced by enhanced fibrinolysis at 45 degrees C: time to reduce the maximal
      turbidity to 20% decreased by 8.6% compared to 37 degrees C and fibrin
      degradation product concentration in the permeation lysis assay was 2-fold to 5
      fold higher than that at 24 degrees C. SSLT exerted its fibrinolytic action on
      fibrin clots under both static and dynamic conditions, whereas plasma clot
      dissolution was observed only in the permeation-driven assay. The improved
      fibrinolytic efficiency of SSLT under dynamic conditions suggests that they may
      serve as a novel therapeutic candidate for dissolution of intravascular thrombi,
      which are typically exposed to permeation forces.

PMID- 28758117
TI  - Neurocardiology: Cardiovascular Changes and Specific Brain Region Infarcts.
AB  - There are complex and dynamic reflex control networks between the heart and the
      brain, including cardiac and intrathoracic ganglia, spinal cord, brainstem, and
      central nucleus. Recent literature based on animal model and clinical trials
      indicates a close link between cardiac function and nervous systems. It is
      noteworthy that the autonomic nervous-based therapeutics has shown great
      potential in the management of atrial fibrillation, ventricular arrhythmia, and
      myocardial remodeling. However, the potential mechanisms of postoperative brain
      injury and cardiovascular changes, particularly heart rate variability and the
      presence of arrhythmias, are not understood. In this chapter, we will describe
      mechanisms of brain damage undergoing cardiac surgery and focus on the
      interaction between cardiovascular changes and damage to specific brain regions.

PMID- 28758118
TI  - Human Brain Mapping of Visual Script Familiarity between Phonological and
      Logographic Language: 3 T Functional MRI Study.
AB  - Neurolinguistic circuitry for two different scripts of language, such as
      phonological scripts (PhonoS) versus logographic scripts (LogoS) (e.g., English
      versus Chinese, resp.), recruits segregated neural pathways according to
      orthographic regularity (OrthoR). The purpose of this study was to identify the
      effect of VSF for cortical representation according to different OrthoR to
      represent Hangul versus Hanja as PhonoS versus LogoS, respectively. A total of 24
      right-handed, native Korean undergraduate students with the first language of
      PhonoS and the second language of LogoS were divided into high- or low-competent
      groups for L2 of LogoS. The implicit word reading task was performed using Hanja
      and Hangul scripts during functional magnetic resonance imaging (fMRI)
      acquisition. Fluctuations of fMRI BOLD signal demonstrated that the LogoS was
      associated with the ventral pathway, whereas PhonoS was associated with the
      dorsal pathway. By interaction analysis, compared with high-competent group, low
      competent group showed significantly greater activation for Hanja than for Hangul
      reading in the right superior parietal lobule area and the left supplementary
      motor area, which might be due to neural efficiency such as attention and
      cognition rather than core neurolinguistic neural demand like OrthoR processing.

PMID- 28758119
TI  - An In Situ and In Silico Evaluation of Biophysical Effects of 27 MHz
      Electromagnetic Whole Body Humans Exposure Expressed by the Limb Current.
AB  - OBJECTIVES: The aim was to evaluate correlations between biophysical effects of
      27 MHz electromagnetic field exposure in humans (limb induced current (LIC)) and
      (1) parameters of affecting heterogeneous electric field and (2) body
      anthropometric properties, in order to improve the evaluation of electromagnetic
      environmental hazards. METHODS: Biophysical effects of exposure were studied in
      situ by measurements of LIC in 24 volunteers (at the ankle) standing near radio
      communication rod antenna and in silico in 4 numerical body phantoms exposed near
      a model of antenna. RESULTS: Strong, positive, statistically significant
      correlations were found in all exposure scenarios between LIC and body volume
      index (body height multiplied by mass) (r > 0.7; p < 0.001). The most informative
      exposure parameters, with respect to the evaluation of electromagnetic hazards by
      measurements (i.e., the ones strongest correlated with LIC), were found to be the
      value of electric field (unperturbed field, in the absence of body) in front of
      the chest (50 cm from body axis) or the maximum value in space occupied by human.
      Such parameters were not analysed in previous studies. CONCLUSIONS: Exposed
      person's body volume and electric field strength in front of the chest determine
      LIC in studied exposure scenarios, but their wider applicability needs further
      studies.

PMID- 28758120
TI  - Corrigendum to "Safety and Efficacy of Small Bowel Examination by Capsule
      Endoscopy for Patients before Liver Transplantation".
AB  - [This corrects the article DOI: 10.1155/2017/8193821.].

PMID- 28758121
TI  - Metabolomics and Cardiology: Toward the Path of Perinatal Programming and
      Personalized Medicine.
AB  - Heart diseases are one of the leading causes of death in Western Countries and
      tend to become chronic, lowering the quality of life of the patients and ending
      up in a massive cost for the Health Systems and the society. Thus, there is a
      growing interest in finding new technologies that would allow the physician to
      effectively treat and prevent cardiac illnesses. Metabolomics is one of the new
      "omics" sciences enabling creation of a photograph of the metabolic state of an
      individual exposed to different environmental factors and pathologies. This
      review analyzed the most recent literature about this technology and its
      application in cardiology in order to understand the metabolic shifts that occur
      even before the manifestation of these pathologies to find possible early
      predictive biomarkers. In this way, it could be possible to find better
      treatments, ameliorate the patient's quality of life, and lower the death rate.
      This technology seems to be so promising that several industries are trying to
      set up kits to immediately assess the metabolites variations in order to provide
      a faster diagnosis and the best treatment specific for that patient, offering a
      further step toward the path of the development of a tailored medicine.

PMID- 28758122
TI  - A Comparison of Genetic Diversity of COX-III Gene in Lowland Chickens and Tibetan
      Chickens.
AB  - To obtain a full understanding of the genetic diversity of the cytochrome oxidase
      III gene (COX-III) and its association with high altitude adaptation in Tibetan
      chickens, we sequenced COX-III in 12 chicken populations (155 Tibetan chickens
      and 145 other domestic chickens). We identified a total of 11 single nucleotide
      polymorphisms (SNPs) and 12 haplotypes (Ha1-Ha12). Low genetic diversity
      (haplotype diversity = 0.531 +/- 0.087, nucleotide diversity = 0.00125) was
      detected for COX-III, and haplotype diversity of Tibetan chicken populations
      (0.750 +/- 0.018) was markedly higher than lowland chicken populations (0.570 +/-
      0.028). Obvious genetic differentiation (nucleotide divergence = 0.092~0.339) and
      conspicuous gene communication (gene flow = 0.33~32.22) among 12 populations
      suggested that Tianfu black-bone fowl (white feather) was possibly introduced
      from Tibetan chicken. SNP m.10587 T>C affects the specific functions of the COX
      enzyme. Haplotype Ha3 was found in Tibetan chickens, and SNP m.10115G>A caused an
      amino acid substitution (Val62Ile) associated with phospholipid binding, while
      mutations m.10017C>A and m.10555G>A and the previously reported SNP m.10065T>C
      reduced the hydropathy index to some extent. Together, this indicates that the
      mitochondrial membrane is more hydrophobic in Tibetan chickens.

PMID- 28758123
TI  - Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid
      System.
AB  - BACKGROUND: Aripiprazole is an antipsychotic drug used to treat schizophrenia and
      related disorders. Our previous study showed that this compound also induces
      antinociceptive effects. The present study aimed to assess the participation of
      the opioid system in this effect. METHODS: Male Swiss mice were submitted to paw
      pressure test and hyperalgesia was induced by intraplantar injection of
      prostaglandin E2 (PGE2, 2 MUg). Aripiprazole was injected 10 min before the
      measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and
      bestatin were given 30 min before aripiprazole. Nociceptive thresholds were
      measured in the 3rd hour after PGE2 injection. RESULTS: Aripiprazole (100
      MUg/paw) injected locally into the right hind paw induced an antinociceptive
      effect that was blocked by naloxone (50 MUg/paw), a nonselective opioid receptor
      antagonist. The role of MU-, delta-, and kappa-opioid receptors was investigated
      using the selective antagonists, clocinnamox (40 MUg/paw), naltrindole (15, 30,
      and 60 MUg/paw), and nor-binaltorphimine (200 MUg/paw), respectively. The data
      indicated that only the delta-opioid receptor antagonist inhibited the peripheral
      antinociception induced by aripiprazole. Bestatin (400 MUg), an aminopeptidase-N
      inhibitor, significantly enhanced low-dose (25 MUg/paw) aripiprazole-induced
      peripheral antinociception. CONCLUSION: The results suggest the participation of
      the opioid system via delta-opioid receptor in the peripheral antinociceptive
      effect induced by aripiprazole.

PMID- 28758124
TI  - The Analysis of Etiology and Risk Factors for 192 Cases of Neonatal Sepsis.
AB  - This study aimed to investigate the etiology and risk factors of neonatal sepsis.
      A retrospective analysis was conducted on 192 patients with sepsis from August
      2013 to March 2015. One hundred and six healthy neonates were used as the control
      group. Logistic regression was used to analyze the risk factors and ROC curve
      analysis performed in laboratory which indicated a significant correlation. The
      results of univariate analysis showed that postnatal age, body weight, and parity
      were significantly related to neonatal sepsis (P < 0.5). Logistic regression
      analysis demonstrated that postnatal age and parity are independent risk factors
      for neonatal sepsis (OR were 1.176 and 0.692, resp., P < 0.001). The maximum area
      underneath the curve (ROCAUC) of soluble CD14 (sCD14-ST), which was the most
      indicative biomarker of sepsis diagnostically, was 0.953 with sensitivity and
      specificity of 93.8% and 84.9%, respectively. Escherichia coli, Staphylococcus
      aureus, and Streptococcus agalactiae were the main bacterial strains causing
      neonatal sepsis, while postnatal age was an independent risk factor for the onset
      of disease. sCD14-ST could be a potential useful diagnostic marker for pediatric
      sepsis.

PMID- 28758125
TI  - Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana
      Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits.
AB  - Diabetes mellitus (DM) is a serious worldwide problem related to human
      hyperglycemia. Thus, herbal preparations with antihyperglycemic properties
      especially leaf extracts of hydroponic Stevia rebaudiana (SR) would be useful in
      hyperglycemia treatment. The antihyperglycemic potential of this medicinal plant
      grown using hydroponics methods has been evaluated. Significant reduction of some
      biochemical characteristics for sugars and fatty acids in blood, liver, and
      muscle especially fasting glucose levels, serum triglycerides, LDL-cholesterol,
      total cholesterol levels, and increased HDL-cholesterol ones was shown with SR
      aqueous extract treatment. Therefore, the aqueous extract of SR is suggested to
      have antihyperglycemic and antihyperlipidemic activity and to restore liver and
      muscle glycogen levels (hepatoprotective effects) in hyperglycemia induced by
      immobilization stress in rabbits and might be recommended for treatment of DM
      (hyperglycemia).

PMID- 28758126
TI  - Efficacy of Eucalyptus cinerea as a Source of Bioactive Compounds for Curative
      Biocontrol of Crown Gall Caused by Agrobacterium tumefaciens Strain B6.
AB  - This research investigated the Eucalyptus cinerea leaves efficiency in the
      Agrobacterium tumefaciens biocontrol, the causative agent of crown gall. GC-MS
      analysis of the essential oil (EO) showed that the main components were 1,8
      cineole (61%) and camphene (15.13%). Thanks to its polyphenols, flavonoids,
      quinones, terpenoids, alkaloids, and tannins richness, the EtOAc-F exhibited the
      most potent antibacterial activity in vitro. Indeed, compared to the other
      fractions, it has the lowest MIC and MBC values of 0.312 mg/mL and 2.5 mg/mL,
      respectively. The GC-MS analysis of EtOAc-F confirmed its richness in
      antibacterial compounds including gallic acid (7.18%), shikimic acid (5.07%), and
      catechin (3.12%). The time-kill curve assay of EtOAc-F (2.5 mg/mL) showed a
      potent bactericidal effect after 20 min of direct contact with A. tumefaciens. In
      planta experiments, gall weights were significantly reduced when EtOAc-F was
      applied at 0.625 and 2.5 mg/wounds. Besides, the disease reduction rates in gall
      weight were 95% and 97.5%, respectively. Interestingly, no phytotoxic effect was
      observed since tomato seeds germinated in the presence of the different
      concentrations of EtOAc-F. These results suggest that EtOAc-F has a good
      potential to be a curative biocontrol agent for crown gall disease.

PMID- 28758127
TI  - Predictors of Inappropriate Use of Diagnostic Tests and Management of
      Bronchiolitis.
AB  - BACKGROUND: The aim of the present study was to determine predictors of
      inappropriate use of diagnostic tests and management of bronchiolitis in a
      population of hospitalized infants. METHODS: In an analytical cross-sectional
      study, we determined independent predictors of the inappropriate use of
      diagnostic tests and management of bronchiolitis in a population of hospitalized
      infants. We defined a composite outcome score as the main outcome variable.
      RESULTS: Of the 303 included patients, 216 (71.3%) experienced an inappropriate
      use of diagnostic tests and treatment of bronchiolitis. After controlling for
      potential confounders, it was found that atopic dermatitis (OR 5.30; CI 95% 1.14
      24.79; p = 0.034), length of hospital stay (OR 1.48; CI 95% 1.08-2.03; p =
      0.015), and the number of siblings (OR 1.92; CI 95% 1.13-3.26; p = 0.015) were
      independent predictors of an inappropriate use of diagnostic tests and treatment
      of the disease. CONCLUSIONS: Inappropriate use of diagnostic tests and treatment
      of bronchiolitis was a highly prevalent outcome in our population of study.
      Participants with atopic dermatitis, a longer hospital stay, and a greater number
      of siblings were at increased risk for inappropriate use of diagnostic tests and
      management of the disease.

PMID- 28758128
TI  - Learning and Treatment of Anaphylaxis by Laypeople: A Simulation Study Using
      Pupilar Technology.
AB  - An anaphylactic shock is a time-critical emergency situation. The decision-making
      during emergencies is an important responsibility but difficult to study. Eye
      tracking technology allows us to identify visual patterns involved in the
      decision-making. The aim of this pilot study was to evaluate two training models
      for the recognition and treatment of anaphylaxis by laypeople, based on expert
      assessment and eye-tracking technology. A cross-sectional quasi-experimental
      simulation study was made to evaluate the identification and treatment of
      anaphylaxis. 50 subjects were randomly assigned to four groups: three groups
      watching different training videos with content supervised by sanitary personnel
      and one control group who received face-to-face training during paediatric
      practice. To evaluate the learning, a simulation scenario represented by an
      anaphylaxis' victim was designed. A device capturing eye movement as well as
      expert valuation was used to evaluate the performance. The subjects that
      underwent paediatric face-to-face training achieved better and faster recognition
      of the anaphylaxis. They also used the adrenaline injector with better precision
      and less mistakes, and they needed a smaller number of visual fixations to
      recognise the anaphylaxis and to make the decision to inject epinephrine.
      Analysing the different video formats, mixed results were obtained. Therefore,
      they should be tested to evaluate their usability before implementation.

PMID- 28758129
TI  - The Association of Haptoglobin Gene Variants and Retinopathy in Type 2 Diabetic
      Patients: A Meta-Analysis.
AB  - AIMS/INTRODUCTION: To collectively evaluate the association between haptoglobin
      (Hp) gene variants and diabetic retinopathy (DR) in patients with type 2 diabetes
      mellitus (T2DM). METHODS: A comprehensive literature review was performed for
      eligible studies. After inclusion and exclusion selection as well as quality
      assessment, those studies meeting quality standards were included. In this study,
      diabetic patients with retinopathy were selected as the case group and those ones
      without DR were treated as the control group. The recessive model, allele model,
      additive model, heterozygote model, and homozygote model were utilized to
      investigate the association of three Hp gene variants and DR. Subgroup analysis
      on different severity of DR including nonproliferative diabetic retinopathy
      (NPDR) and proliferative diabetic retinopathy (PDR) was also conducted. RESULTS:
      Six trials from different regions were finally included. A total of 1145 subjects
      containing 564 T2DM patients with retinopathy were included. The recessive model,
      allele model, additive model, and homozygote model results showed that Hp gene
      variants were not associated with DR, NPDR, and PDR. However, the heterozygote
      model indicated the association of Hp gene variants with DR. CONCLUSIONS: No
      association was found between the Hp gene variants and PDR and NPDR. More studies
      are required to verify these findings.

PMID- 28758130
TI  - Proinsulin Promotes Self-Renewal of a Hematopoietic Progenitor Cell Line In
      Vitro.
AB  - The objective of this study was to assess the effects of exogenously expressed
      proinsulin on the biological characters of a hematopoietic stem cell line (HSC)
      and erythroid myeloid lymphoid (EML) cells and explore new strategies for cell
      therapy for type I diabetes. EML cells were transduced with lentivirus particles
      carrying the human proinsulin (proINS) gene. The positive transduced cells were
      selected based on green fluorescence protein (GFP) positivity and puromycin
      resistance. Overexpression of proINS was confirmed via real-time PCR and Western
      blotting. The functional activity of the human proINS secreted by EML cells was
      elucidated by analyzing the activation of insulin receptor and its downstream
      signaling. Pro-INS + EML cells were able to prime the phosphorylation of insulin
      receptor as well as induce the expression of downstream genes of insulin
      receptor. Furthermore, Wnt3a can significantly promote self-renewal of Pro-INS +
      EML cells. However, we did not observe significant changes in the proliferation
      and differentiation of INS + EML cells, compared to the control EML cells. Our
      results might be useful for developing a new therapy for diabetes mellitus.

PMID- 28758132
TI  - New Insights for Immune-Based Diagnosis and Therapy for Infectious Diseases.

PMID- 28758131
TI  - Treatment of Diabetes Mellitus Using iPS Cells and Spice Polyphenols.
AB  - Diabetes mellitus is a chronic disease that threatens human health. The disease
      is caused by a metabolic disorder of the endocrine system, and long-term illness
      can lead to tissue and organ damage to the cardiovascular, endocrine, nervous,
      and urinary systems. Currently, the disease prevalence is 11.4%, the treatment
      rate is 48.2%, and the mortality rate is 2.7% worldwide. Comprehensive and
      effective control of diabetes, as well as the use of insulin, requires further
      study to develop additional treatment options. Here, we reviewed the current
      reprogramming of somatic cells using specific factors to induced pluripotent stem
      (iPS) cells capable of repairing islet beta cell damage in diabetes patients to
      treat patients with type 1 diabetes mellitus. We also discuss the shortcomings
      associated with clinical use of iPS cells. Additionally, certain polyphenols
      found in spices might improve glucose homeostasis and insulin resistance in
      diabetes patients, thereby constituting promising options for the treatment of
      type 2 diabetes.

PMID- 28758133
TI  - Probiotic Lactobacillus Strains Stimulate the Inflammatory Response and Activate
      Human Macrophages.
AB  - Lactobacilli have been shown to promote health functions. In this study, we
      analyzed the mechanism by which four different strains of probiotics affected
      innate immunity, such as regulation of ROS, cytokines, phagocytosis, bactericidal
      activity, signaling by NF-kappaB pp65, and TLR2 activation. The production of ROS
      was dependent on the concentration and species of Lactobacillus. The results
      obtained from the tested strains (Lactobacillus rhamnosus GG, L. rhamnosus KLSD,
      L. helveticus IMAU70129, and L. casei IMAU60214) showed that strains induced
      early proinflammatory cytokines such as IL-8,TNF-alpha, IL-12p70, and IL-6.
      However, IL-1beta expression was induced only by L. helveticus and L. casei
      strains (after 24 h stimulation). Phagocytosis and bactericidal activity of
      macrophages against various pathogens, such as S. aureus, S. typhimurium, and E.
      coli, were increased by pretreatment with Lactobacillus. The nuclear
      translocation NF-kappaB pp65 and TLR2-dependent signaling were also increased by
      treatment with the probiotics. Taken together, the experiments demonstrate that
      probiotic strains of Lactobacillus exert early immunostimulatory effects that may
      be directly linked to the initial inflammation of the response of human
      macrophages.

PMID- 28758134
TI  - Polymorphism rs2073618 of the TNFRSF11B (OPG) Gene and Bone Mineral Density in
      Mexican Women with Rheumatoid Arthritis.
AB  - Osteoporosis (OP) is highly prevalent in rheumatoid arthritis (RA) and is
      influenced by genetic factors. Single-nucleotide polymorphism (SNP) rs2073618 in
      the TNFRSF11B osteoprotegerin (OPG) gene has been related to postmenopausal OP
      although, to date, no information has been described concerning whether this
      polymorphism is implied in abnormalities of bone mineral density (BMD) in RA. We
      evaluated, in a case-control study performed in Mexican-Mestizo women with RA,
      whether SNP rs2073618 in the TNFRSF11B gene is associated with a decrease in BMD.
      RA patients were classified as follows: (1) low BMD and (2) normal BMD. All
      patients were genotyped for the rs2073618 polymorphism by PCR-RFLP. The frequency
      of low BMD was 74.4%. Higher age was observed in RA with low BMD versus normal
      BMD (62 and 54 years, resp.; p < 0.001). Worse functioning and lower BMI were
      observed in RA with low BMD (p = 0.003 and p = 0.002, resp.). We found similar
      genotype frequencies in RA with low BMD versus RA with normal BMD (GG genotype
      71% versus 64.4%, GC 26% versus 33%, and CC 3% versus 2.2%, resp.; p = 0.6). We
      concluded that in Mexican-Mestizo female patients with RA, the rs2073618
      polymorphism of the TNRFS11B gene is not associated with low BMD.

PMID- 28758135
TI  - Effect of Chitosan and Liposome Nanoparticles as Adjuvant Codelivery on the
      Immunoglobulin G Subclass Distribution in a Mouse Model.
AB  - BACKGROUND: We investigate the immunogenic properties of chitosan and liposome
      nanoparticles as adjuvant codelivery against a commercial pneumococcal conjugate
      vaccine (PCV) in an animal model. METHODS: The chitosan and liposome
      nanoparticles were prepared by ionic gelation and dry methods, respectively. The
      PCV immunization was performed intradermally in the presence of adjuvants and
      booster injections which were given without an adjuvant. The Quil-A(r) was used
      as a control adjuvant. The ELISA was performed to measure the antibodies against
      pneumococcal type 14 polysaccharide (Pn14PS). RESULTS: The level of total
      antibodies against Pn14PS antigen was no different between the mouse groups with
      or without adjuvant codelivery. Codelivery of the PCV with chitosan nanoparticles
      as well as the Quil-A adjuvant elicited IgG1, IgG2a, IgG2b, and IgG3 antibodies.
      Meanwhile, codelivery of liposome nanoparticles elicited mainly IgG1 antibodies
      against the Pn14PS. CONCLUSIONS: The chitosan and liposome nanoparticles as
      adjuvant codelivery were successfully synthesized. These nanoparticles have
      different shapes in particle formation, liposome nanoparticle with their
      unilamellar shape and chitosan nanoparticles in large shape due to the
      aggregation of small-size particles. Codelivery of chitosan nanoparticles has
      more effect on the IgG subclass antibody production than that of liposome
      nanoparticles in a mouse model.

PMID- 28758136
TI  - A mouse Model of Focal Vascular Injury Induces Astrocyte Reactivity, Tau
      Oligomers, and Aberrant Behavior.
AB  - Neuropsychiatric symptom development has become more prevalent with 270,000 blast
      exposures occurring in the past 10 years in the United States. How blast injury
      leads to neuropsychiatric symptomology is currently unknown. Preclinical models
      of blast-induced traumatic brain injury have been used to demonstrate blood-brain
      barrier disruption, degenerative pathophysiology, and behavioral deficits.
      Vascular injury is a primary effect of neurotrauma that can trigger secondary
      injury cascades and neurodegeneration. Here we present data from a novel scaled
      and clinically relevant mouse blast model that was specifically developed to
      assess the outcome of vascular injury. We look at the biochemical effects and
      behavioral changes associated with blast injury in young-adult male BALB/c mice.
      We report that blast exposure causes focal vascular injury in the Somatosensory
      Barrel Field cortex, which leads to perivascular astrocyte reactivity, as well as
      acute aberrant behavior. Biochemical analysis revealed that mild blast exposure
      also invokes tauopathy, neuroinflammation, and oxidative stress. Overall, we
      propose our model to be used to evaluate focal blood-brain barrier disruption and
      to discover novel therapies for human neuropsychiatric symptoms.

PMID- 28758137
TI  - Sciatic Nerve Injury After Proximal Hamstring Avulsion and Repair.
AB  - BACKGROUND: Muscle bellies of the hamstring muscles are intimately associated
      with the sciatic nerve, putting the sciatic nerve at risk of injury associated
      with proximal hamstring avulsion. There are few data informing the magnitude of
      this risk, identifying risk factors for neurologic injury, or determining
      neurologic outcomes in patients with distal sciatic symptoms after surgery.
      PURPOSE: To characterize the frequency and nature of sciatic nerve injury and
      distal sciatic nerve-related symptoms after proximal hamstring avulsion and to
      characterize the influence of surgery on these symptoms. STUDY DESIGN: Cohort
      study; Level of evidence, 3. METHODS: This was a retrospective review of patients
      with proximal partial or complete hamstring avulsion. The outcome of interest was
      neurologic symptoms referable to the sciatic nerve distribution below the knee.
      Neurologic symptoms in operative patients were compared pre- and postoperatively.
      RESULTS: The cohort consisted of 162 patients: 67 (41.4%) operative and 95
      (58.6%) nonoperative. Sciatic nerve-related symptoms were present in 22 operative
      and 23 nonoperative patients, for a total of 45 (27.8%) patients (8 [4.9%] motor
      deficits, 11 [6.8%] sensory deficits, and 36 [22.2%] with neuropathic pain).
      Among the operative cohort, 3 of 3 (100.0%) patients showed improvement in their
      motor deficit postoperatively, 3 of 4 (75.0%) patients' sensory symptoms
      improved, and 17 of 19 (89.5%) patients had improvement in pain. A new or
      worsening deficit occurred in 5 (7.5%) patients postoperatively (2 [3.1%] motor
      deficits, 1 [1.5%] sensory deficit, and 3 [4.5%] with new pain). Predictors of
      operative intervention included lower age (odds ratio [OR], 0.952; 95% CI, 0.921
      0.982; P = .001) and complete avulsion (OR, 10.292; 95% CI, 2.526-72.232; P <
      .001). Presence of neurologic deficit was not predictive. CONCLUSION: Sciatic
      nerve-related symptoms after proximal hamstring avulsion are underrecognized.
      Currently, neurologic symptoms are not considered when determining whether to
      pursue operative intervention. Given the high likelihood of improvement with
      surgical treatment, neurologic symptoms should be considered when making a
      decision regarding operative treatment.

PMID- 28758138
TI  - Author Name Disambiguation for PubMed.
AB  - Log analysis shows that PubMed users frequently use author names in queries for
      retrieving scientific literature. However, author name ambiguity may lead to
      irrelevant retrieval results. To improve the PubMed user experience with author
      name queries, we designed an author name disambiguation system consisting of
      similarity estimation and agglomerative clustering. A machine-learning method was
      employed to score the features for disambiguating a pair of papers with ambiguous
      names. These features enable the computation of pairwise similarity scores to
      estimate the probability of a pair of papers belonging to the same author, which
      drives an agglomerative clustering algorithm regulated by 2 factors: name
      compatibility and probability level. With transitivity violation correction, high
      precision author clustering is achieved by focusing on minimizing false-positive
      pairing. Disambiguation performance is evaluated with manual verification of
      random samples of pairs from clustering results. When compared with a state-of
      the-art system, our evaluation shows that among all the pairs the lumping error
      rate drops from 10.1% to 2.2% for our system, while the splitting error rises
      from 1.8% to 7.7%. This results in an overall error rate of 9.9%, compared with
      11.9% for the state-of-the-art method. Other evaluations based on gold standard
      data also show the increase in accuracy of our clustering. We attribute the
      performance improvement to the machine-learning method driven by a large-scale
      training set and the clustering algorithm regulated by a name compatibility
      scheme preferring precision. With integration of the author name disambiguation
      system into the PubMed search engine, the overall click-through-rate of PubMed
      users on author name query results improved from 34.9% to 36.9%.

PMID- 28758139
TI  - Assaying the Effects of Splice Site Variants by Exon Trapping in a Mammalian Cell
      Line.
AB  - There are several in silico programs that endeavor to predict the functional
      impact of an individual's sequence variation at splice donor/acceptor sites, but
      experimental confirmation is problematic without a source of RNA from the
      individual that carries the variant. With the aid of an exon trapping vector,
      such as pSPL3, an investigator can test whether a splice site sequence change
      leads to altered RNA splicing, through expression of reference and variant mini
      genes in mammalian cells and analysis of the resultant RNA products.

PMID- 28758140
TI  - Endogenous C-terminal Tagging by CRISPR/Cas9 in Trypanosoma cruzi.
AB  - To achieve the C-terminal tagging of endogenous proteins in T. cruzi we use the
      Cas9/pTREX-n vector (Lander et al., 2015) to insert a specific tag sequence (3xHA
      or 3xc-Myc) at the 3' end of a specific gene of interest (GOI). Chimeric sgRNA
      targeting the 3' end of the GOI is PCR-amplified and cloned into Cas9/pTREX-n
      vector. Then a DNA donor molecule to induce DNA repair by homologous
      recombination is amplified. This donor sequence contains the tag sequence and a
      marker for antibiotic resistance, plus 100 bp homology arms corresponding to
      regions located right upstream of the stop codon and downstream of the Cas9
      target site at the GOI locus. Vectors pMOTag23M (Oberholzer et al., 2006) or
      pMOHX1Tag4H (Lander et al., 2016b) are used as PCR templates for DNA donor
      amplification. Epimastigotes co-transfected with the sgRNA/Cas9/pTREX-n construct
      and the DNA donor cassette are then cultured for 5 weeks with antibiotics for
      selection of double resistant parasites. Endogenous gene tagging is finally
      verified by PCR and Western blot analysis.

PMID- 28758141
TI  - Isolation and Infection of Drosophila Primary Hemocytes.
AB  - Phagocytosis of invading pathogens and their subsequent clearance in lysosomes is
      important for organismal fitness. We have devised the following protocol to
      extract phagocytic hemocytes from wild-type and mutant Drosophila larvae and
      infect the isolated hemocytes with GFP-labeled E. coli to measure the rate of
      phagocytosis and degradation within individual hemocytes over time.

PMID- 28758142
TI  - Emerging Roles for Platelets in Inflammation and Disease.
AB  - Platelets and their interaction with cells of the immune system contribute
      through a variety of molecular mechanisms to support hemostasis and inflammation.
      These simple yet essential cells exert their effects in lymphocytes, monocytes,
      and neutrophils, both recruiting and modulating their function after activation.
      Emerging evidence is starting to define the mechanisms that allow platelets to
      also play pivotal roles in host defense. For example, platelet cell-surface
      expression of toll-like receptors allows platelets to direct neutrophil
      activation toward extracellular trap formation and facilitate the elimination of
      blood pathogens. In addition to these well-known receptors, two of the most
      recently discovered platelet receptors, C-type lectin receptor 2 (CLEC-2), and
      TREM-like transcript-1 (TLT-1), have been shown to modulate hemostatic and
      inflammation-related roles in platelets. This review will discuss the evolution
      of our understanding of platelet functions from hemostasis to inflammation, and
      highlight novel mechanisms that platelets use to mediate hemostasis under
      inflammatory pressure.

PMID- 28758143
TI  - Mentoring for Success in Tobacco Regulatory Science: A Qualitative Study.
AB  - OBJECTIVES: Our study explores the experiences of early career and senior
      scientists regarding mentorship and career trajectories in tobacco regulatory
      science (TRS). METHODS: We conducted 22 phone interviews with early career and
      senior tobacco regulatory scientists from July 2015 to January 2016. All
      interviews were conducted using a structured interview guide and analyzed using a
      thematic approach by 2 independent coders. RESULTS: TRS presents specific
      opportunities and challenges to scientists due to its focused goal of informing
      tobacco regulation. An understanding of US Food and Drug Administration (FDA)
      research priorities and how science can inform tobacco regulation are essential
      for effective mentorship in TRS. Careers in TRS can be pursued in various
      academic and non-academic professional roles; both offer the distinct ability to
      conduct science that impacts public policy. Early career and senior scientists
      identified the importance and challenge of providing broad training across the
      diverse disciplines of TRS. CONCLUSIONS: Effective mentorship in TRS requires
      that mentors possess an in-depth understanding of the scientific, regulatory, and
      legislative processes inherent to tobacco regulatory policy-making. A training
      program for mentors specific to TRS has the potential to meet diverse
      professional needs of mentors and mentees aiming to impact tobacco policy.

PMID- 28758144
TI  - Immune signaling mechanisms of PTSD risk and symptom development: insights from
      animal models.
AB  - Post-traumatic stress disorder (PTSD) is characterized by persistent re
      experiencing of a traumatic event, avoidance, and increased arousal. The approved
      pharmacological treatments for PTSD have limited efficacy (~60% treatment
      response), supporting the need for identification of biomarkers and novel
      pharmacological therapies. Mounting evidence suggests increased inflammatory
      markers and altered immune gene expression correlate with the severity of
      symptoms in PTSD patients. However a causal role of immune signaling in
      development and maintenance of PTSD symptoms is not clear, as inflammation may
      also be an epiphenomenon related to metabolic and behavioral effects of stress.
      Animal studies have been critical in understanding the potential causal role of
      immune signaling in PTSD. In this review we will present the most recent
      evidence, primarily focusing on the last 3 years, for inflammatory dysfunction
      both preceding and following PTSD, and how animal models of PTSD have contributed
      to our understanding of immune mechanisms involved in enduring anxiety after
      trauma. We will particularly focus on the role of peripheral vs. central immune
      signaling, the differences between single vs. chronic stress models of PTSD and
      recent utilization of these models to investigate novel anti-inflammatory
      treatments. We also highlight some current gaps in the literature including
      models of TBI/PTSD comorbidity, lack of translational peripheral markers of
      inflammation and the relatively incomplete understanding of the inflammatory
      trajectory after severe stress.

PMID- 28758145
TI  - Cross-validation of optimized composites for preclinical Alzheimer's disease.
AB  - INTRODUCTION: We discuss optimization and validation of composite endpoints for
      pre-symptomatic Alzheimer's clinical trials. Optimized composites offer hope of
      substantial gains in statistical power or reduction in sample size. But there is
      tradeoff between optimization and face validity such that optimization should
      only be considered if there is a convincing rationale. As with statistically
      derived regions of interest in neuroimaging, validation on independent datasets
      is essential. METHODS: Using four datasets, we consider the optimized weighting
      of four components of a cognitive composite which includes measures of (1) global
      cognition, (2) semantic memory, (3) episodic memory, and (4) executive function.
      Weights are optimized to either discriminate amyloid positivity or maximize power
      to detect a treatment effect in an amyloid positive population. We apply repeated
      5*3-fold cross-validation to quantify the out-of-sample performance of optimized
      composite endpoints. RESULTS: We found the optimized weights varied greatly
      across the folds of the cross validation with either optimization method. Both
      optimization methods tend to down-weight the measures of global cognition and
      executive function. However when these optimized composites were applied to the
      validation sets, they did not provide consistent improvements in power. In fact,
      overall, the optimized composites performed worse than those without
      optimization. DISCUSSION: We find that component weight optimization does not
      yield valid improvements in sensitivity of this composite to detect treatment
      effects.

PMID- 28758148
TI  - Horizontal convective boiling of R448A, R449A, and R452B within a micro-fin tube.
AB  - This article presents local convective boiling measurements in a micro-fin tube
      for three low global warming potential refrigerants: R448A, R449A, and R452B. An
      existing correlation was modified to predict multi-component mixtures, which
      predicted 98% of the measurements to within +/-20%. The new correlation was used
      to compare the heat transfer coefficient of the three test fluids at the same
      heat flux, saturated refrigerant temperature, and refrigerant mass flux. The
      resulting comparison showed that refrigerant R452B exhibited the highest heat
      transfer, in large part due to its approximately 28% larger liquid thermal
      conductivity and smaller temperature glide as compared to the tested low-global
      warming potential refrigerants. For the example case, the heat transfer
      coefficient for R449A was approximately 8% larger than that for R448A, while the
      heat transfer coefficient for R452B was more than 59% larger than either R448A or
      R449A. The heat transfer coefficients for R448A and R449A were roughly between 26
      and 48% less than that of R404A for the example case. In contrast, the model
      predicts that the R452B heat transfer coefficient was approximately 13% larger
      than that of R404A for the same conditions.

PMID- 28758147
TI  - CREATE-X a role for capecitabine in early-stage breast cancer: an analysis of
      available data.
AB  - Breast cancer patients with residual disease after neoadjuvant chemotherapy and
      surgery may benefit from additional anti-cancer therapies. Capecitabine, an oral
      antimetabolite and prodrug of 5-Flurouracil, has been approved for treating
      metastatic breast cancer. One randomized clinical trial (CREATE-X) of
      capecitabine versus no additional therapy has been conducted in women with early
      stage breast cancer who received standard chemotherapy pre-operative therapy and
      had residual invasive breast cancer at the time of surgery. Results from CREATE
      X, showed that capecitabine had a statistically significant survival advantage
      compared with no additional therapy. This perspective provides a review and
      analysis of the available data from CREATEx in the context of results from other
      adjuvant trials of capecitabine in early stage breast cancer that had disease
      free survival as a primary endpoint. We conclude that although the previously
      published studies of capecitabine in the adjuvant setting did not meet their
      primary endpoint, the data from these studies are consistent with the hypothesis
      that capecitabine may offer additional survival benefit in patients with chemo
      refractory breast cancer at the time of surgery after receiving standard
      chemotherapy. In these patients, offering a course of adjuvant capecitabine or
      enrolling the patient in a clinical trial are appropriate therapeutic options.
      The patient should be informed about both the increased survival observed in the
      CREATEx trial and the expected toxicities from capecitabine chemotherapy.

PMID- 28758146
TI  - Effects of traumatic brain injury and posttraumatic stress disorder on
      development of Alzheimer's disease in Vietnam Veterans using the Alzheimer's
      Disease Neuroimaging Initiative: Preliminary Report.
AB  - INTRODUCTION: Traumatic brain injury (TBI) and posttraumatic stress disorder
      (PTSD) have previously been reported to be associated with increased risk of
      Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans
      with/without mild cognitive impairment with a history of at least one TBI and/or
      ongoing PTSD to determine whether these contribute to the development of AD.
      METHODS: Potential subjects identified by Veterans Administration records
      underwent an initial telephone screen. Consented subjects underwent clinical
      evaluation, lumbar puncture, structural MRI and amyloid PET scans. RESULTS: We
      observed worse cognitive functioning in PTSD and TBI + PTSD groups, worse global
      cognitive functioning in the PTSD group, lower superior parietal volume in the
      TBI + PTSD group, and lower amyloid positivity in the PTSD group, but not the TBI
      group compared to controls without TBI/PTSD. Medial temporal lobe atrophy was not
      increased in the PTSD and/or TBI groups. DISCUSSION: Preliminary results do not
      indicate that TBI or PTSD increase the risk for AD measured by amyloid PET.
      Additional recruitment, longitudinal follow-up, and tau PET scans will provide
      more information in the future.

PMID- 28758149
TI  - Adiponectin and its Hydrolase-Activated Receptors.
AB  - The relevance of adiponectin to insulin sensitivity has been elucidated over the
      last two decades. As a promoter of ceramide degradation, it works through its
      cognate receptors, AdipoR1 and AdipoR2, to alter bioactive sphingolipid species.
      Adiponectin diminishes the accumulation of ceramide, a lipid metabolite which can
      play a causal role in obesity-induced insulin resistance. Concurrently,
      adiponectin stimulates the production of sphingosine-1-phosphate (S1P), a cyto
      protective molecule that accentuates adiponectin's positive metabolic effects.
      This review focuses on recent work that solidifies knowledge of the adiponectin
      signaling pathway, gives new insight into some notable characteristics of
      adiponectin's receptors, and most importantly, affirms adiponectin receptor
      agonism as a viable therapeutic tool to combat elevated ceramide levels and
      improve insulin sensitivity in obese patients with type II diabetes.

PMID- 28758150
TI  - Diabetes and Cardioplegia.
AB  - Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is associated
      with injury to the vasculature and microcirculation leading to coronary
      microvascular dysfunction, permeability changes and cardiac dysfunction. In the
      setting of cardiopulmonary bypass with cardioplegia, poorly-controlled diabetes
      is associated with significant changes in endothelium-dependent and independent
      vascular dysfunction, vascular reactivity, vascular permeability, protein
      expression, cell death, coronary/peripheral microcirculation and reduced
      vasomotor tone leading to hypotension and impaired endothelial function. The gene
      expression profiles after cardiopulmonary bypass with cardioplegic arrest is
      quantitatively and qualitatively different in patients with diabetes. Gene
      expression profiling capitalizing on the differences between patients with and
      without diabetes is a good place to identify potential medical targets.

PMID- 28758152
TI  - Sleep Deprivation Disrupts Recall of Conditioned Fear Extinction.
AB  - BACKGROUND: Learned fear is crucial in the development and maintenance of
      posttraumatic stress disorder (PTSD) and other anxiety disorders, and extinction
      of learned fear is necessary for response to exposure-based treatments. In
      humans, research suggests disrupted sleep impairs consolidation of extinction,
      though no studies have examined this experimentally using total sleep
      deprivation. METHODS: Seventy-one healthy controls underwent a paradigm to
      acquire conditioned fear to a visual cue. Twenty-four hours after fear
      conditioning, participants underwent extinction learning. Twenty-four hours after
      extinction learning, participants underwent extinction recall. Participants were
      randomized to three groups: 1) well-rested throughout testing ("normal sleep"; n
      = 21); 2) 36 hours total sleep deprivation before extinction learning ("pre
      extinction deprivation"; n = 25); or 3) 36 hours total sleep deprivation after
      extinction learning and before extinction recall ("post-extinction deprivation";
      n = 25). The groups were compared on blink EMG reactivity to the condition
      stimulus during extinction learning and recall. RESULTS: There were no
      differences among the three groups during extinction learning. During extinction
      recall, the pre-extinction deprivation group demonstrated significantly less
      extinction recall than the normal sleep group. There was no significant
      difference between the normal sleep and post-extinction deprivation group during
      extinction recall. Results indicated sleep deprivation prior to extinction
      training significantly disrupts extinction recall. CONCLUSIONS: These findings
      suggest that (1) sleep deprivation in the immediate aftermath of trauma could be
      a potential contributor to PTSD development and maintenance via interference with
      natural extinction processes and (2) management of sleep symptoms should be
      considered during extinction-based therapy.

PMID- 28758151
TI  - The effect of diet-induced serum hypercholesterolemia on the surfactant system
      and the development of lung injury.
AB  - Acute respiratory distress syndrome (ARDS) is a pulmonary disorder associated
      with alterations to the pulmonary surfactant system. Recent studies showed that
      supra-physiological levels of cholesterol in surfactant contribute to impaired
      function. Since cholesterol is incorporated into surfactant within the alveolar
      type II cells which derives its cholesterol from serum, it was hypothesized that
      serum hypercholesterolemia would predispose the host to the development of lung
      injury due to alterations of cholesterol content in the surfactant system. Wistar
      rats were randomized to a standard lab diet or a high cholesterol diet for 17-20
      days. Animals were then exposed to one of three models of lung injury: i) acid
      aspiration ii) ventilation induced lung injury, and iii) surfactant depletion.
      Following physiological monitoring, lungs were lavaged to obtain and analyze the
      surfactant system. The physiological results showed there was no effect of the
      high cholesterol diet on the severity of lung injury in any of the three models
      of injury. There was also no effect of the diet on surfactant cholesterol
      composition. Rats fed a high cholesterol diet had a significant impairment in
      surface tension reducing capabilities of isolated surfactant compared to those
      fed a standard diet exposed to the surfactant depletion injury. In addition, only
      rats that were exposed to ventilation induced lung injury had elevated levels of
      surfactant associated cholesterol compared to non-injured rats. It is concluded
      that serum hypercholesterolemia does not predispose rats to altered surfactant
      cholesterol composition or to lung injury. Elevated cholesterol within surfactant
      may be a marker for ventilation induced lung damage.

PMID- 28758153
TI  - Cell Plasma Membrane Cholesterol as a Diagnostic.
AB  - Cholesterol is a tightly regulated major structural component of the cell plasma
      membrane (PM) where it forms stoichiometric complexes with phospholipids and
      sphingolipids. The amount of cholesterol in the PM exhibits a regulatory role in
      basal activity of several biomolecular processes by direct binding to proteins
      and by indirect local environmental effects within the PM that are also coupled
      to overall cellular cholesterol homeostasis. The term "active cholesterol" refers
      to PM cholesterol not complexed to lipids, a cholesterol state that arises above
      a threshold mole fraction of cholesterol in the PM. Active cholesterol level in
      the PM provides a control mechanism for cellular cholesterol homeostasis through
      its recognition by membrane bound proteins that activate genes of cholesterol
      synthesis enzymes. Uptake of LDL, production and release of HDL as well as
      reversible storage of cholesterol in the cytosol by covalent modification are
      also regulated and dependent on PM cholesterol (thermodynamic) activity: active
      cholesterol. A number of human disease states have been found to have associated
      alterations in PM cholesterol and thus a method for its determination is
      described.

PMID- 28758154
TI  - A Dollars and "Sense" Exploration of Vape Shop Spending and E-cigarette Use.
AB  - INTRODUCTION: Across the US, vape shops have emerged to provide e-cigarette users
      access to products not usually available at gas stations or retail stores. As
      vape shop sales have steadily increased, so have questions about the impact of
      marketing and price on e-cigarette use behaviors. In this exploratory analysis,
      we aim to characterize spending on e-cigarettes and evaluate the association with
      customer perceptions and use behaviors. METHODS: In a cross-sectional survey of
      vape shop customers (n=78), perceptions and use of e-cigarettes and tobacco
      products were assessed. Descriptive statistics and multivariate logistic
      regression were used to evaluate the association between spending and
      socioeconomic factors, demographics, and use behaviors. RESULTS: Overall,
      spending amounts ranged from less than $10/month to more than $250/month, with a
      median around $50-75/month. Males spent more than females (p=0.003), but spending
      did not significantly differ by age (p=0.13). Customers who spent more than
      $50/month used lower levels of nicotine (mg/ml) (p=0.003) but a greater quantity
      of e-liquid (ml/month) (p<0.0001) compared to customers who spent under that
      amount. Mod use and intention to use e-cigarettes as a cessation device were
      significantly associated with vape shop spending in the regression model (OR=
      17.5; 95% CI= (4.3, 70.2) and OR=0.22; 95% CI= (0.06, 0.75), respectively).
      CONCLUSIONS: Spending appears to be significantly associated with e-cigarette use
      behaviors. Making "sense" of the potential relationships between the dollars
      spent at vape shops and consumer use behaviors is important as regulations for e
      cigarette sales are proposed.

PMID- 28758155
TI  - APOL1 renal-risk variants do not associate with incident cardiovascular disease
      or mortality in the Systolic Blood Pressure Intervention Trial.
AB  - INTRODUCTION: Relationships between apolipoprotein L1 gene (APOL1) renal-risk
      variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify
      associations between APOL1 and CVD, 2,568 African American Systolic Blood
      Pressure Intervention Trial (SPRINT) participants were assessed for the incidence
      of CVD events (primary composite including non-fatal myocardial infarction, acute
      coronary syndrome not resulting in myocardial infarction, nonfatal stroke, non
      fatal acute decompensated heart failure, and CVD death), renal outcomes, and all
      cause mortality. METHODS: Cox proportional hazards regression models were
      employed adjusting for age, sex, African ancestry proportion, and treatment group
      (systolic blood pressure target of <120 mm Hg versus <140 mm Hg). RESULTS:
      Fourteen percent of participants had two APOL1 RRVs; these individuals also had
      lower baseline estimated GFR and higher levels of albuminuria and BMI. After a
      median follow-up of 39 months, no significant association was observed between
      APOL1 RRVs and the primary composite CVD outcome, any of its components, or all
      cause mortality (recessive or additive genetic models). APOL1 demonstrated a
      trend toward association with sustained 30% reduction in estimated GFR to <60
      ml/min/1.73m2 in those with normal kidney function at baseline (hazard ratio [95%
      CI] 1.64 [0.85-2.93]; p=0.114, recessive model). CONCLUSION: APOL1 RRVs were not
      associated with incident CVD in high-risk hypertensive, non-diabetic African
      American participants in SPRINT.

PMID- 28758156
TI  - Varicella Zoster Virus and Large Vessel Vasculitis, the Absence of an
      Association.
AB  - OBJECTIVE: It is controversial whether microorganisms play a role in the
      pathogenesis of large and medium vessel vasculitides (eg, giant cell arteritis
      [GCA], Takayasu arteritis [TAK] and focal idiopathic aortitis [FIA]). Recent
      studies have reported the presence of Varicella Zoster Virus (VZV) within
      formalin-fixed, paraffin-embedded temporal arteries and aortas of about three
      quarters or more of patients with these conditions, and in a minority of
      controls. In a prospective study, we sought to confirm these findings using DNA
      extracted from vessels that were harvested under surgically aseptic conditions
      and snap frozen. METHODS AND RESULTS: DNA samples extracted from 11 surgically
      sterile temporal arteries and 31 surgically sterile thoracic aortas were used in
      an attempt to identify the vessel-associated VZV genome. Two different validated
      PCR methods were used. Thirty-one thoracic aorta aneurysm specimens included
      biopsies from 8 patients with GCA, 2 from patients with TAK, 6 from patients with
      FIA, and 15 from patients without vasculitis, who had non-inflammatory aneurysms.
      Eleven temporal artery biopsies were collected from 5 patients with GCA and 6
      controls. The presence of VZV was not identified in either the specimens from
      patients with large vessel vasculitis or from the controls. CONCLUSIONS: Using
      surgically sterile snap-frozen specimens, we were unable to confirm recent
      reports of the presence of VZV in either aortas or temporal arteries from
      patients with large vessel vasculitis or controls.

PMID- 28758157
TI  - Theory of Kondo suppression of spin polarization in nonlocal spin valves.
AB  - We theoretically analyze contributions from the Kondo effect to the spin
      polarization and spin diffusion length in all-metal nonlocal spin valves.
      Interdiffusion of ferromagnetic atoms into the normal metal layer creates a
      region in which Kondo physics plays a significant role, giving discrepancies
      between experiment and existing theory. We start from a simple model and
      construct a modified spin drift-diffusion equation which clearly demonstrates how
      the Kondo physics not only suppresses the electrical conductivity but even more
      strongly reduces the spin diffusion length. We also present an explicit
      expression for the suppression of spin polarization due to Kondo physics in an
      illustrative regime. We compare this theory to previous experimental data to
      extract an estimate of the Elliot-Yafet probability for Kondo spin flip
      scattering of 0.7 +/- 0.4, in good agreement with the value of 2/3 derived in the
      original theory of Kondo.

PMID- 28758158
TI  - Simulating Clinical Trials With and Without Intracranial EEG Data.
AB  - OBJECTIVE: It is currently unknown if knowledge of clinically silent
      (electrographic) seizures improves the statistical efficiency of clinical trials.
      METHODS: Using data obtained from 10 patients with chronically implanted subdural
      electrodes over an average of 1 year, a Monte Carlo bootstrapping simulation
      study was performed to estimate the statistical power of running a clinical trial
      based on A) patient reported seizures with intracranial EEG (icEEG) confirmation,
      B) all patient reported events, or C) all icEEG confirmed seizures. A "drug" was
      modeled as having 10%, 20%, 30%, 40% and 50% efficacy in 1000 simulated trials
      each. Outcomes were represented as percentage of trials that achieved p<0.05
      using Fisher Exact test for 50%-responder rates (RR50), and Wilcoxon Rank Sum
      test for median percentage change (MPC). RESULTS: At each simulated drug
      strength, the MPC method showed higher power than RR50. As drug strength
      increased, statistical power increased. For all cases except RR50 with drug of
      10% efficacy, using patient reported events (with or without icEEG confirmation)
      was not as statistically powerful as using all available intracranially confirmed
      seizures (p<0.001). SIGNIFICANCE: This study demonstrated using simulation that
      additional accuracy in seizure detection using chronically implanted icEEG
      improves statistical power of clinical trials. Newer invasive and noninvasive
      seizure detection devices may have the potential to provide greater statistical
      efficiency, accelerate drug discovery and lower trial costs.

PMID- 28758159
TI  - Fast, accurate, small-scale 3D scene capture using a low-cost depth sensor.
AB  - Commercially available depth sensing devices are primarily designed for domains
      that are either macroscopic, or static. We develop a solution for fast microscale
      3D reconstruction, using off-the-shelf components. By the addition of lenses,
      precise calibration of camera internals and positioning, and development of
      bespoke software, we turn an infrared depth sensor designed for human-scale
      motion and object detection into a device with mm-level accuracy capable of
      recording at up to 30Hz.

PMID- 28758160
TI  - Sphingomyelin encrypts tissue factor: ATP-induced activation of A-SMase leads to
      tissue factor decryption and microvesicle shedding.
AB  - A majority of tissue factor (TF) on cell surfaces exists in an encrypted state
      with minimal to no procoagulant activity. At present, it is unclear whether
      limited availability of phosphatidylserine (PS) and/or a specific membrane lipid
      in the outer leaflet of the plasma membrane contributes to TF encryption.
      Sphingomyelin (SM) is a major phospholipid in the outer leaflet, and SM
      metabolism is shown to be altered in many disease settings that cause thrombotic
      disorders. The present study is carried out to investigate the effect of SM
      metabolism on TF activity and TF+ microvesicles (MVs) release. In vitro studies
      using TF reconstituted into liposomes containing varying molar ratios of SM
      showed that a high molar ratio of SM in the proteoliposomes inhibits TF coagulant
      activity. Treatment of macrophages with sphingomyelinase (SMase) that hydrolyzes
      SM in the outer leaflet results in increased TF activity at the cell surface and
      TF+ MVs release without increasing PS externalization. Adenosine triphosphate
      (ATP) stimulation of macrophages that activates TF and induces MV shedding also
      leads to translocation of acid-sphingomyelinase (A-SMase) to the plasma membrane.
      ATP stimulation increases the hydrolysis of SM in the outer leaflet. Inhibition
      of A-SMase expression or activity not only attenuates ATP-induced SM hydrolysis,
      but also inhibits ATP-induced TF decryption and TF+ MVs release. Overall, our
      novel findings show that SM plays a role in maintaining TF in an encrypted state
      in resting cells and hydrolysis of SM following cell injury removes the
      inhibitory effect of SM on TF activity, thus leading to TF decryption.

PMID- 28758161
TI  - Intraductal Papillary Mucinous Neoplasm and Pancreas Divisum: Two Cases.
AB  - BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are a
      subset of ductal cell tumors with potential for malignancy. Because it is
      difficult to predict whether and when they will become malignant, management and
      resection are widely debated. CASE 1: A 70-year-old male with a 1-year history of
      epigastric pain was found to have pancreas divisum with a dominant 2.4 cm
      multicystic uncinate process lesion communicating with the main pancreatic duct
      and associated uncinate duct dilation. CASE 2: An 83-year-old male with pancreas
      divisum had a 7.3 cm uncinate cystic lesion with mural nodularity that had
      increased in size from 2.1 cm in 2008. CONCLUSION: Management of patients with
      IPMNs can be challenging and may require resection to prevent malignant
      transformation.

PMID- 28758162
TI  - Individual-level factors associated with the risk of acquiring human Plasmodium
      knowlesi malaria in Malaysia: a case-control study.
AB  - BACKGROUND: The emergence of human malaria due to the monkey parasite Plasmodium
      knowlesi threatens elimination efforts in southeast Asia. Changes in land use are
      thought to be driving the rise in reported P knowlesi cases, but the role of
      individual-level factors is unclear. To address this knowledge gap we assessed
      human and environmental factors associated with zoonotic knowlesi malaria risk.
      METHODS: We did this population-based case-control study over a 2 year period in
      the state of Sabah in Malaysia. We enrolled cases with microscopy-positive, PCR
      confirmed malaria who presented to two primary referral hospitals serving the
      adjacent districts of Kudat and Kota Marudu. We randomly selected three malaria
      negative community controls per case, who were matched by village within 2 weeks
      of case detection. We obtained questionnaire data on demographics, behaviour, and
      residential malaria risk factors, and we also assessed glucose-6-phosphate
      dehydrogenase (G6PD) enzyme activity. We used conditional logistic regression
      models to evaluate exposure risk between P knowlesi cases and controls, and
      between P knowlesi and human-only Plasmodium spp malaria cases. FINDINGS: From
      Dec 5, 2012, to Jan 30, 2015, we screened 414 patients and subsequently enrolled
      229 cases with P knowlesi malaria mono-infection and 91 cases with other
      Plasmodium spp infection. We enrolled 953 matched controls, including 683 matched
      to P knowlesi cases and 270 matched to non-P knowlesi cases. Age 15 years or
      older (adjusted odds ratio [aOR] 4.16, 95% CI 2.09-8.29, p<0.0001), male gender
      (4.20, 2.54-6.97, p<0.0001), plantation work (3.50, CI, 1.34-9.15, p=0.011),
      sleeping outside (3.61, 1.48-8.85, p=0.0049), travel (2.48, 1.45-4.23, p=0.0010),
      being aware of the presence of monkeys in the past 4 weeks (3.35, 1.91-5.88,
      p<0.0001), and having open eaves or gaps in walls (2.18, 1.33-3.59, p=0.0021)
      were independently associated with increased risk of symptomatic P knowlesi
      infection. Farming occupation (aOR 1.89, 95% CI 1.07-3.35, p=0.028), clearing
      vegetation (1.89, 1.11-3.22, p=0.020), and having long grass around the house
      (2.08, 1.25-3.46, p=0.0048) increased risk for P knowlesi infection but not other
      Plasmodium spp infection. G6PD deficiency seemed to be protective against P
      knowlesi (aOR 0.20, 95% CI 0.04-0.96, p=0.045), as did residual insecticide
      spraying of household walls (0.52, 0.31-0.87, p=0.014), with the presence of
      young sparse forest (0.35, 0.20-0.63, p=00040) and rice paddy around the house
      (0.16, 0.03-0.78, 0.023) also associated with decreased risk. INTERPRETATION:
      Adult men working in agricultural areas were at highest risk of knowlesi malaria,
      although peri-domestic transmission also occurrs. Human behavioural factors
      associated with P knowlesi transmission could be targeted in future public health
      interventions. FUNDING: United Kingdom Medical Research Council, Natural
      Environment Research Council, Economic and Social Research Council, and
      Biotechnology and Biosciences Research Council.

PMID- 28758163
TI  - Shared Calendars for Home Health Management.
AB  - What is the role of shared calendars for home health management? Utilizing a
      maximum variation sampling method, we interviewed 20 adult individuals with
      diabetes and 20 mothers of children with asthma to understand calendar use in the
      context of chronic disease home health management. In comparing the experiences
      of these two groups, we explore participants' use of tools for organizing tasks
      and appointments, their strategies for capturing health and non-health events in
      the family calendar system, the ecology of artifacts that intersect with their
      scheduling tools, and the failures they experienced while managing their calendar
      systems. Through this work, we offer a context-specific perspective of schedule
      management strategies for individuals and families who must integrate their
      handling of chronic illnesses with everyday living.

PMID- 28758164
TI  - Precision Spectroscopy to Enable Traceable Dynamic Measurements of Pressure.
AB  - We present recent work aimed at creating a standard for the dynamic measurement
      of pressure. A near-IR laser spectroscopy system is demonstrated for measuring 8
      cm-1 in 50 MUs with a 4 kHz repetition rate.

PMID- 28758165
TI  - Analyzing the Moving Parts of a Large-Scale Multi-Label Text Classification
      Pipeline: Experiences in Indexing Biomedical Articles.
AB  - Medical subject headings (MeSH) is a controlled hierarchical vocabulary used by
      the National Library of Medicine (NLM) to index biomedical articles. In the 2014
      version of MeSH terminology there are a total of 27,149 terms. Librarians at the
      NLM tag each biomedical article to be indexed for the PubMed literature search
      system with terms from MeSH. This means the human indexers look at each article's
      full text and index it with a small set of descriptors, 13 on average, from over
      27,000 descriptors available in MeSH. There have been many recent attempts to
      automate this process focused on using the article title and abstract text to
      predict MeSH terms for the corresponding article. There has also been an open
      automated biomedical indexing challenge, BioASQ [1], that started in 2013. The
      best general supervised learning framework in these challenges has been a
      pipeline with four different components: 1. pre-processing and feature
      extraction; 2. employing the binary relevance and/or nearest neighbor approaches
      to select a set of candidate terms; 3. ranking these candidate terms using
      corresponding informative features; and 4. applying label calibration to
      dynamically predict the number of top terms to be included in the final selection
      for the current instance. The specific details in how each of these components is
      implemented determines the performance variations of various entries in the
      challenge. In this paper, we analyze these moving parts of the MeSH indexing
      multi-label classification pipeline with experiments involving different
      combinations. Our best combination achieves ~ 1% increase in micro F-score
      compared with the top performing team across the five weeks of the final batch of
      the BioASQ 2014 challenge. The main take away from our efforts is that small
      improvements/modifications to different components of the pipeline can offer
      moderate improvements to the overall performance of the method. Our experiences
      show that, at least thus far, top performances have resulted mostly due to these
      improvements rather than drastic changes of the core methodology.

PMID- 28758166
TI  - A coconut oil-rich meal does not enhance thermogenesis compared to corn oil in a
      randomized trial in obese adolescents.
AB  - BACKGROUND: Consumption of medium chain triglycerides (MCT) in overweight adults
      increases thermogenesis and improves weight management. Coconut oil is a rich
      natural source of MCT, but its thermogenic effect is unknown. Our study evaluated
      the effects of a test oil enriched in coconut oil, on energy expenditure,
      satiety, and metabolic markers in a randomized, double blind, cross-over study.
      METHODS AND FINDINGS: Fifteen children, age 13-18 years, body mass index >85th
      percentile for age and sex, were enrolled. Two test meals, containing 20 g of fat
      from either corn oil or a coconut oil-enriched baking fat (1.1 g of fatty acids
      with chain lengths <= 10C), were administered. A fasting blood sample was taken
      before breakfast and at 30, 45, 60, 120, and 180 min post-meal for measurement of
      metabolites. Thermic effect of food (TEF) was assessed over 6 h using indirect
      calorimetry. Satiety was measured using visual analog scales (VAS). There was no
      significant effect of fat type, time, or fat type * time interaction on TEF,
      appetite/satiety, glucose, and insulin area under the curve. There was a
      significant effect of fat type on leptin (P=0.027), triglycerides (P=0.020) and
      peptide YY (P=0.0085); leptin and triglyceride concentrations were lower and
      peptide YY concentrations were higher with corn oil consumption. CONCLUSION: A
      coconut oil-enriched baking fat does not enhance thermogenesis and satiety in
      children. Given that this is the only current study of its kind, more research is
      needed into the use of coconut oil as a tool in weight management in overweight
      and obese children.

PMID- 28758167
TI  - Joint Data Harmonization and Group Cardinality Constrained Classification.
AB  - To boost the power of classifiers, studies often increase the size of existing
      samples through the addition of independently collected data sets. Doing so
      requires harmonizing the data for demographic and acquisition differences based
      on a control cohort before performing disease specific classification. The
      initial harmonization often mitigates group differences negatively impacting
      classification accuracy. To preserve cohort separation, we propose the first
      model unifying linear regression for data harmonization with a logistic
      regression for disease classification. Learning to harmonize data is now an
      adaptive process taking both disease and control data into account. Solutions
      within that model are confined by group cardinality to reduce the risk of
      overfitting (via sparsity), to explicitly account for the impact of disease on
      the inter-dependency of regions (by grouping them), and to identify disease
      specific patterns (by enforcing sparsity via the l0-'norm'). We test those
      solutions in distinguishing HIV-Associated Neurocognitive Disorder from Mild
      Cognitive Impairment of two independently collected, neuroimage data sets; each
      contains controls and samples from one disease. Our classifier is impartial to
      acquisition difference between the data sets while being more accurate in
      diseases seperation than sequential learning of harmonization and classification
      parameters, and non-sparsity based logistic regressors.

PMID- 28758168
TI  - Unsupervised Medical Subject Heading Assignment Using Output Label Co-occurrence
      Statistics and Semantic Predications.
AB  - Librarians at the National Library of Medicine tag each biomedical abstract to be
      indexed by their Pubmed information system with terms from the Medical Subject
      Headings (MeSH) terminology. The MeSH terminology has over 26,000 terms and
      indexers look at each article's full text to assign a set of most suitable terms
      for indexing it. Several recent automated attempts focused on using the article
      title and abstract text to identify MeSH terms for the corresponding article.
      Most of these approaches used supervised machine learning techniques that use
      already indexed articles and the corresponding MeSH terms. In this paper, we
      present a novel unsupervised approach using named entity recognition,
      relationship extraction, and output label co-occurrence frequencies of MeSH term
      pairs from the existing set of 22 million articles already indexed with MeSH
      terms by librarians at NLM. The main goal of our study is to gauge the potential
      of output label co-occurrence statistics and relationships extracted from free
      text in unsupervised indexing approaches. Especially, in biomedical domains,
      output label co-occurrences are generally easier to obtain than training data
      involving document and label set pairs owing to the sensitive nature of textual
      documents containing protected health information. Our methods achieve a micro F
      score that is comparable to those obtained using supervised machine learning
      techniques with training data consisting of document label set pairs. Baseline
      comparisons reveal strong prospects for further research in exploiting label co
      occurrences and relationships extracted from free text in recommending terms for
      indexing biomedical articles.

PMID- 28758169
TI  - Diterpenoids from Isodon species: an update.
AB  - Covering: December 2005 to June 2016. Previous review: Nat. Prod. Rep., 2006, 23,
      673-698Over the last decade, great efforts have been made to conduct
      phytochemistry research on the genus Isodon, which have led to the isolation and
      identification of a number of diterpenoids. At the same time, these newly
      reported diterpenoids with diverse structures have led to new findings on their
      biological functions and chemical synthesis research. In this update, we review
      more than 600 new diterpenoids, including their structures, classifications,
      biogenetic pathways, bioactivities, and chemical synthesis.

PMID- 28758172
TI  - Erratum to: Screening of Blood Levels of Mercury, Cadmium, and Copper in Pregnant
      Women in Dakahlia, Egypt: New Attention to an Old Problem.

PMID- 28758171
TI  - QTL Mapping for Resistance to Iridovirus in Asian Seabass Using Genotyping-by
      Sequencing.
AB  - Identifying quantitative trait loci (QTL) for viral disease resistance is of
      particular importance in selective breeding programs of fish species. Genetic
      markers linked to QTL can be useful in marker-assisted selection (MAS) for elites
      resistant to specific pathogens. Here, we conducted a genome scan for QTL
      associated with Singapore grouper iridovirus (SGIV) resistance in an Asian
      seabass (Lates calcarifer) family, using a high-density linkage map generated
      with genotyping-by-sequencing. One genome-wide significant and three suggestive
      QTL were detected at LG21, LG6, LG13, and LG15, respectively. The phenotypic
      variation explained (PVE) by the four QTL ranged from 7.5 to 15.6%. The position
      of the most significant QTL at LG21 was located between 31.88 and 36.81 cM. The
      SNP marker (SNP130416) nearest to the peak of this QTL was significantly
      associated with SGIV resistance in an unrelated multifamily population. One
      candidate gene, MECOM, close to the peak of this QTL region, was predicted.
      Evidence of alternative splicing was observed for MECOM and one specific category
      of splicing variants was differentially expressed at 5 days post-SGIV infection.
      The QTL detected in this study are valuable resources and can be used in the
      selective breeding programs of Asian seabass with regard to resistance to SGIV.

PMID- 28758173
TI  - Academic and Government Partnerships to Address Diabetes in the USA: a Narrative
      Review.
AB  - PURPOSE OF REVIEW: Multi-sector partnerships are broadly considered to be of
      value for diabetes prevention and management. The purpose of this article is to
      summarize academic and government collaborations focused on diabetes prevention
      and management. RECENT FINDINGS: Using a narrative review approach, we identified
      17 articles describing 10 academic and government partnerships for diabetes
      management and surveillance. Challenges and gaps in the literature include
      complexity of diabetes management vis a vis current healthcare infrastructure; a
      paucity of racial/ethnic diversity in translational efforts; and the time/effort
      needed to maintain strong relationships across partner institutions. Academic and
      government partnerships are of value for diabetes prevention and management
      activities. Acknowledgment that the key priorities of government programming are
      often costs and feasibility is critical for collaborations to be successful.
      Future translational efforts of diabetes prevention and management programs
      should focus on the following: (1) expansion of partnerships between academia and
      local health departments; (2) increased utilization of implementation science for
      enhanced and efficient implementation and dissemination; and (3) harnessing of
      technological advances for data analysis, patient communication, and report
      generation.

PMID- 28758174
TI  - Prioritising Causal Genes at Type 2 Diabetes Risk Loci.
AB  - PURPOSE OF REVIEW: Genome-wide association studies (GWAS) for type 2 diabetes
      (T2D) risk have identified a large number of genetic loci associated with disease
      susceptibility. However, progress moving from association signals through causal
      genes to functional understanding has so far been slow, hindering clinical
      translation. This review discusses the benefits and limitations of emerging,
      unbiased approaches for prioritising causal genes at T2D risk loci. RECENT
      FINDINGS: Candidate causal genes can be identified by a number of different
      strategies that rely on genetic data, genomic annotations, and functional
      screening of selected genes. To overcome the limitations of each particular
      method, integration of multiple data sets is proving essential for establishing
      confidence in the prioritised genes. Previous studies have also highlighted the
      need to support these efforts through identification of causal variants and
      disease-relevant tissues. Prioritisation of causal genes at T2D risk loci by
      integrating complementary lines of evidence promises to accelerate our
      understanding of disease pathology and promote translation into new therapeutics.

PMID- 28758170
TI  - Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence,
      structure, and function.
AB  - Covering: up to January 2017Cytochrome P450 enzymes (P450s) are some of the most
      exquisite and versatile biocatalysts found in nature. In addition to their well
      known roles in steroid biosynthesis and drug metabolism in humans, P450s are key
      players in natural product biosynthetic pathways. Natural products, the most
      chemically and structurally diverse small molecules known, require an extensive
      collection of P450s to accept and functionalize their unique scaffolds. In this
      review, we survey the current catalytic landscape of P450s within the
      Streptomyces genus, one of the most prolific producers of natural products, and
      comprehensively summarize the functionally characterized P450s from Streptomyces.
      A sequence similarity network of >8500 P450s revealed insights into the sequence
      function relationships of these oxygen-dependent metalloenzymes. Although only
      ~2.4% and <0.4% of streptomycete P450s have been functionally and structurally
      characterized, respectively, the study of streptomycete P450s involved in the
      biosynthesis of natural products has revealed their diverse roles in nature,
      expanded their catalytic repertoire, created structural and mechanistic
      paradigms, and exposed their potential for biomedical and biotechnological
      applications. Continued study of these remarkable enzymes will undoubtedly expose
      their true complement of chemical and biological capabilities.

PMID- 28758175
TI  - Next generation sequencing of progressive colorectal liver metastases after
      portal vein embolization.
AB  - : Portal vein embolization (PVE) can be required to stimulate liver regeneration
      before hepatectomy for colorectal liver metastasis (CRCLM), however PVE may also
      trigger CRCLM progression in patients initially exhibiting chemotherapy response.
      Using RNA-seq, we aimed to determine the molecular networks involved in
      metastatic progression in this context. A prospective study including all CRCLM
      patients undergoing PVE prior to hepatectomy was conducted. Paired biopsies of
      metastatic lesions were obtained prior to and after PVE and total RNA was
      isolated and used to prepare Illumina rRNA-depleted TruSeq stranded cDNA
      libraries for HiSeq 100 bp paired-end sequencing. Patients were classified with
      progression of disease (PDPVE) or stable disease (SDPVE) post-PVE using 3D-CT
      tumor volumetric analysis. RESULTS: Twenty patients were included, 13 (65.0%) in
      the PDPVE group (median 58.0% (18.6-234.3) increase in tumor volume) and 7
      (35.0%) in the SDPVE group exhibiting continuous chemotherapy response (median 
      14.3% (-40.8 to -2.8) decrease in tumor volume) (p < 0.0001). Our results showed
      that progressive CRCLM after PVE undergo gene expression changes that indicate
      activation of core cancer pathways (IL-17 (p = 5.94 * 10-03), PI3K (p = 8.71 * 10
      03), IL6 and IGF-1 signaling pathways), consistent with changes driven by
      cytokines and growth factors. Differential expression analysis in a paired model
      of progression (EdgeR, DeSeq) identified significantly dysregulated genes in the
      PDPVE group (FOS, FOSB, RAB20, IRS2). CONCLUSION: Differentially expressed genes
      and pathways with known links to cancer and metastasis were identified post-PVE
      in patients with disease progression. Highlighting these molecular changes is a
      crucial first step towards development of targeted therapeutic strategies that
      may mitigate the effects of PVE on tumor growth.

PMID- 28758178
TI  - Exposure of medical staff to radiation during osteosynthesis of proximal femoral
      fracture: descriptive analysis and comparison of different devices.
AB  - BACKGROUND: The use of fluoroscopy is necessary during proximal femoral fracture
      (PFF) osteosynthesis. The frequency of these procedures justifies a description
      of radiation exposure and comparisons between different techniques and between
      the different surgical team members. METHODS: This observational prospective and
      comparative study includes a series of 68 patients with PFF receiving
      osteosynthesis. Radiation exposure was assessed for all members of the operating
      team. The radiation dose measurements for the different members of the surgical
      team during PFF osteosynthesis were compared. The factors affecting the radiation
      dose were investigated. RESULTS: The mean active dosimeter readings for each
      operation were 7.39 uSv for the primary surgeon, 3.93 uSv for the assistant
      surgeon, 1.92 uSv for the instrument nurse, 1.25 uSv for the circulating nurse,
      and 0.64 uSv for the anaesthesiologist, respectively. Doses decreased
      significantly between these different members of the medical team (all p <
      0.001). The dose also varied with patient age and BMI, as well as with
      fluoroscopy time and operating time, but not with type of fracture or type of
      osteosynthesis. CONCLUSION: Medical staff receives significantly different doses
      depending on their position in relation to the radiation source. Operating time
      and fluoroscopy time are the modifiable factors that affect the radiation dose.
      The radiation doses received by the different members of the medical teams
      involved in proximal femur osteosynthesis procedures all fall below the doses
      recommended by the International Commission on Radiation Units and Measurements.

PMID- 28758176
TI  - Antidepressant-like Effect of Bacopaside I in Mice Exposed to Chronic
      Unpredictable Mild Stress by Modulating the Hypothalamic-Pituitary-Adrenal Axis
      Function and Activating BDNF Signaling Pathway.
AB  - Preliminary studies conducted in our laboratory have confirmed that Bacopaside I
      (BS-I), a saponin compound isolated from Bacopa monnieri, displayed
      antidepressant-like activity in the mouse behavioral despair model. The present
      investigation aimed to verify the antidepressant-like action of BS-I using a
      mouse model of behavioral deficits induced by chronic unpredictable mild stress
      (CUMS) and further probe its underlying mechanism of action. Mice were exposed to
      CUMS for a period of 5 consecutive weeks to induce depression-like behavior.
      Then, oral gavage administrations with vehicle (model group), fluoxetine (12
      mg/kg, positive group) or BS-I (5, 15, 45 mg/kg, treated group) once daily were
      started during the last two weeks of CUMS procedure. The results showed that BS-I
      significantly ameliorated CUMS-induced depression-like behaviors in mice, as
      characterized by an elevated sucrose consumption in the sucrose preference test
      and reduced immobility time without affecting spontaneous locomotor activity in
      the forced swimming test, tail suspension test and open field test. It was also
      found that BS-I treatment reversed the increased level of plasma corticosterone
      and decreased mRNA and protein expressions of glucocorticoid receptor induced by
      CUMS exposure, indicating that hypothalamic-pituitary-adrenal (HPA) axis
      hyperactivity of CUMS-exposed mice was restored by BS-I treatment. Furthermore,
      chronic administration of BS-I elevated expression levels of brain-derived
      neurotrophic factor (BDNF) (mRNA and protein) and activated the phosphorylation
      of extracellular signal-regulated kinase and cAMP response element-binding
      protein in the hippocampus and prefrontal cortex in mice subjected to CUMS
      procedure. Taken together, these results indicated that BS-I exhibited an obvious
      antidepressant-like effect in mouse model of CUMS-induced depression that was
      mediated, at least in part, by modulating HPA hyperactivity and activating BDNF
      signaling pathway.

PMID- 28758179
TI  - Clinical Outcomes of Posterior C1 and C2 Screw-Rod Fixation for Atlantoaxial
      Instability.
AB  - AIM: In this study, we aimed at sharing our experiences and contributing to the
      literature by making a retrospective analysis of the patients we operated with
      screw-rod system for atlantoaxial instability in our clinic. MATERIAL AND
      METHODS: Archive files of adult patients, who were operated for posterior C1-C2
      stabilization with screw and rod in our clinic between January 2006 and January
      2016, were analyzed. 28 patients, who had pre and post-operative images, follow
      up forms and who were followed for at least one year, were analyzed. Preoperative
      clinical and radiological records, preoperative observations, postoperative
      complications, and clinical responses were evaluated. RESULTS: The average age of
      28 patients (F:13 M:19) was 44.7 (21-73). Fixation was performed with C1-C2 screw
      rod system on the basis of the following diagnoses; type 2 odontoid fracture
      (16), basilar invagination (5), C1-C2 instability (5), and atlantoaxial
      subluxation secondary to rheumatoid arthritis (2). Lateral mass screws were
      inserted at C1 segment. C2 screws inserted were bilateral pedicle in 12 cases,
      bilateral pars in 4, bilateral laminar in 8 and one side pars, one side laminar
      in 4 cases. There was no screw malposition. Neither implant failure nor recurrent
      instability was observed during follow-up. Significant clinical improvement was
      reported according to the assessments done with JOA and VAS scores. CONCLUSION:
      C1-C2 screw fixation is regarded as a more successful and safe method than other
      fixation methods in surgical treatment of atlantoaxial instability considering
      complications, success in reduction, fusion and fixation strength. C2 laminar
      screw technique is as successful as the other alternatives in fixation and
      fusion.

PMID- 28758180
TI  - Surgical strategies for thoracic myelopathy due to ossification of ligamentum
      flavum: A technical note based on radiological type.
AB  - AIM: Ossification of the ligamentumflavum (OLF) is a primary cause of thoracic
      myelopathy. A relatively safe surgical technique based on radiological type is
      described for the OLF-induced thoracic myelopathy. MATERIAL AND METHODS: Forty
      patients with thoracic myelopathy caused by OLF were studied retrospectively. The
      OLF was divided into fused and non-fused types according to the CT and MRI
      findings. All patients underwent posterior decompression. For the fused type,
      open-door laminectomy and for the non-fused type, French-door laminectomy
      surgical techniques were adopted. Pre-operation, post-operative, and follow-up
      neurological status were evaluated using the modified Japanese Orthopaedic
      Association (mJOA) score. RESULTS: The mean duration of symptoms was 9.2+/-11.5
      and 8.4+/-9.7months in the non-fused and fused groups, respectively. The apex of
      OLF at the most severely compressed level was located at 2.7+/-1.9mm above the
      disc level: 2.4+/-1.6 and 3.0+/-2.2mm in the non-fused and fused groups,
      respectively. The preoperative mJOA scores were 5.0+/-1.1 and 4.2+/-0.9 in the
      non-fused and fused groups, respectively. After the operation, the neurological
      deficits in all patients improved. With an average follow-up of 33.9 months, the
      mJOA score ultimately improved in both groups. CONCLUSION: In OLF-induced
      thoracic myelopathy, the en bloc elevation of the laminae with the OLF plaque is
      emphasized at the key site for surgical decompression. Based on the present
      classification of OLF, different surgical strategies should be adopted for a safe
      neurological decompression.

PMID- 28758177
TI  - The 5-year outcomes of moderately hypofractionated radiotherapy (66 Gy in 22
      fractions, 3 fractions per week) for localized prostate cancer: a retrospective
      study.
AB  - BACKGROUND: Hypofractionated radiotherapy using fewer and larger fractional doses
      may be more beneficial than conventional external-beam radiotherapy for localized
      prostate cancer. We evaluated the 5-year outcomes of moderately hypofractionated
      radiotherapy for localized prostate cancer. METHODS: We retrospectively evaluated
      195 patients with localized prostate cancer (T1-3N0M0) who underwent intensity
      modulated radiotherapy (IMRT) (66 Gy delivered in fractions of 3 Gy every other
      weekday) between May 2005 and December 2011. Patients received androgen
      deprivation therapy depending on the perceived intermediate or high risk of their
      disease. A prostate-specific antigen nadir +2.0 ng/ml indicated biochemical
      failure. We assessed toxicity using the Radiation Therapy Oncology Group and the
      European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria,
      and patient-reported outcomes using the Expanded Prostate Cancer Index Composite
      (EPIC). RESULTS: The risk classifications (proportion) were low risk (13.8%),
      intermediate risk (35.9%), and high risk (50.3%). The median follow-up was 69
      months. Thirteen (6.66%) patients experienced biochemical failure within a median
      of 40 months (interquartile range, 25-72 months). The 5-year overall survival
      rate and no biological evidence of disease rate were 97.7% and 92.4%,
      respectively. Based on the RTOG/EORTC criteria, no patient experienced acute or
      late toxicity of grade 3 or higher. The EPIC scores revealed significant
      differences in the average value of all domains (p < 0.01). At 1 month
      postradiotherapy completion, the general urinary and bowel domain scores had
      decreased, but these scores returned to baseline level by 3 months post
      radiotherapy. CONCLUSIONS: The moderately hypofractionated radiotherapy protocol
      yielded short-term satisfactory clinical outcomes with acceptable toxicity.

PMID- 28758181
TI  - How Cranial Shapes Led to Contemporary Ethnic Classification: A Historical View.
AB  - In the medical literature, various ethnic terms such as Caucasian or
      Mongolian,are sporadically cited to indicate the relationship between certain
      disorders and the geographical origin of individuals. Few scientists recognize
      that those definitions stem from a medical thesis written by the German physician
      Johann Friedrich Blumenbach in 1775. Through considering cranial shapes,
      Blumenbach proposed five race varieties including the Caucasian, the Mongolian,
      the Malayan, the Ethiopian, and the American. While he favored only beauty, his
      contemporaries reclaimed an intellectuality arrangement among those race types
      and gave the highest credibility to Caucasian, which therefore, besides defining
      an ethnicity, has conveyed a discriminatory meaning. The term had been widely
      used in the medical literature without knowledge of its historical background.
      Although not commonly used any longer, the Caucasian and similar terms that
      reflect racial preference should be abandoned in medical text and replaced by
      more favorable definitions.

PMID- 28758182
TI  - Which is better Stainless Steel or Titanium alloy?
AB  - AIM: To investigate immunologic reactions after implantation of stainless steel
      (SS) alloy and titanium (Ti) alloy in a rat model. Macrophage and cytokine
      responses have been reported after the in vivo and in vitro application of
      different biomaterials. MATERIAL AND METHODS: Wistar albino rats after an
      exploration of the thoracolumbar paravertebral muscle tissue of the subjects,
      group I underwent a sham surgery, and groups II and III were implanted Ti alloy
      and SS alloy rods respectively. The CD4, CD8, CD25 (IL-2R) (lymphocyte and CD4
      gate), CD4+CD8+ and CD4+CD25+Foxp3+ (Tregs), IL-4, IL-10, IL-6, IL-17A, TGF-beta,
      TNF-alpha in the blood were analyzed. RESULTS: CD4, CD25 (IL-2R), CD4+CD8+ and
      Tregs levels were lower in the Group III compared to the sham and Group IIs. IL
      6, IL-17A, TGF-beta and TNF-alpha levels in the G III showed a significant
      increase on all days in comparison with the sham and Group II. IL-4 and IL-10
      levels, were lower in the Group III than those in the Group II; and a significant
      decrease was observed in the IL-10 level. While there was a reduction in IL-6 and
      IL-17A levels in the Group II as opposed to the sham group. CONCLUSION: As
      opposed to SS alloy, Ti alloy suppresses the development of inflammations by
      inhibiting proinflammatory response; strengthens the humoral immune system by
      intensifying the antibody-dependent immune response; triggers the development of
      immune tolerance by regulating the immune response; and activates the mechanism
      that prevents immune response-related damage from occurring.

PMID- 28758183
TI  - Neuronavigation-guided endoscopic endonasal excision of schwannoma-like chordoma
      of the Meckel's cave: A case report.
AB  - Chordomas are locally aggressive malignant tumors due to their recurrence
      potential, originating from the embryonic notochord remnants. Chordomas can
      originate anywhere on the axial skeleton. They are extradural and are spread by
      bone destruction. Chordomas are locally aggressive tumors which invade the dura
      mater, and may also present with secondary intradural growth. The Meckel's cave
      location of chordomas has been very rarely reported in the literature. Chordomas
      located in the Meckel's cave can be radiologically confused with trigeminal
      schwannomas. Herein, we report a case of chordoma located in the Meckel's cave
      which was successfully excised through neuronavigation-guided endoscopic
      endonasal excision which is commonly used in the skull base surgeries.

PMID- 28758185
TI  - Cystic Chordoma Of Cavernous Sinus.
AB  - Chordomas are the tumors commonly involving base of skull which are predominantly
      solid in consistency. A cystic chordoma of cavernous sinus is an extremely rare
      entity and has never been reported. We report a 26- year-old male presenting with
      gradually progressive right sided sixth nerve palsy and headache. Computerized
      tomography (CT) scan and Magnetic resonant imaging (MRI ) scan of brain showed a
      cystic lesion in right cavernous sinus.Patient was successfully treated using
      transnasal endoscopic trans-sphenoidal approach . Histopathological examination
      of lesion revealed chordoma.Our case is the first report of such condition.
      Chordoma should be considered as a differential diagnosis of cystic lesion in
      parasellar location. We briefly review the radiology, the pathology and
      management dilemmas of such lesions .

PMID- 28758184
TI  - Motor Evoked Potentials and Bispectral Index-Guided Anaesthesia in Image-Guided
      Mini-Invasive Neurosurgery of Supratentorial Tumors Nearby the Cortico-Spinal
      Tract.
AB  - AIM: To describe and evaluate the anaesthesiological regimen used in
      neurophysiologically monitored image-guided mini-invasive neurosurgery. MATERIAL
      AND METHODS: Twenty-four patients underwent elective surgery under general
      anaesthesia that was administered through Target Controlled Infusion (TCI) for
      effect-site concentration (Ce) of Propofol and Remifentanil, targeting the
      Bispectral Index (BIS) in the 40-60 intervals. The stimulating intensity of
      transcranial motor evoked potentials (tMEP), BIS, Propofol and Remifentanil Ce
      were collected at MEPs threshold (T) definition (respectively BIS@T, CeProp@T and
      CeRemi@T). Intraoperative seizure, explicit recall for intraoperative awareness
      and clinical motor status were assessed. RESULTS: CeProp@T and CeRemi@T ranged
      respectively between 1.5-2.2 MUg/ml (Median 1.6 MUg/ml) and 3.5-18 ng/ml (Median
      8 ng/ml) that were effective in keeping the BIS@T between 40 and 60 in all
      surgeries. tMEP thresholds ranged between 45 and 120 mA. There was no correlation
      between CeProp@T, CeRemi@T and tMEP, as well as between BIS@T and respectively
      tMEP, CeProp@T, CeRemi@T. None of patients had induced electrical seizure or
      explicit recalls. Motor scores were equal to preoperative values in 22/24
      patients. CONCLUSION: BIS-guided general anaesthesia within a 40-60 interval,
      with low Ce of Propofol (<=2 MU/ml) and high analgesic regime allow reliable tMEP
      measurements, avoiding postoperative neurological impairment and major adverse
      outcomes, such as seizure and awareness.

PMID- 28758186
TI  - The Causes of Post-Operative Meningitis: The Comparison Of Gram-Negative and Gram
      Positive Pathogens.
AB  - AIM: In this study, we aim to determine the microbiological etiology in
      critically ill neurosurgical patients with nosocomial meningitis (NM) and show
      the impact of Gram-negative rods and differences of patient's characteristics,
      clinical and prognostic measures between Gram-negative and Gram-positive
      meningitis. MATERIAL AND METHODS: In this prospective, one center study we
      reviewed all adult patients hospitalized during a 12-year period and identified
      pathogens isolated from post-neurosurgical cases of NM. Demographic, clinical,
      and treatment characteristics were noted from the medical records. RESULTS: Of
      the 134 bacterial NM patients, 78 were male and 56 were female, with a mean age
      of 46+/-15.9 and median age of 50 (18-80) years. 141 strains isolated; 82 (58.2%)
      were Gram negative, 59 (41.8%) were Gram positive. Most common isolated
      microorganism was Acinetobacter baumannii (%34.8). In comparison of mortality
      data shows that the patients who have meningitis with Gram-negative pathogens
      have higher mortality than with Gram positives (p=0.034). The duration between
      surgery and meningitis was shorter in Gram negative meningitis cases compared to
      others (p=0.045) but the duration between the diagnosis and death was shorter in
      Gram-positive meningitis cases compared to Gram negatives (p= 0.017). CSF protein
      and lactate level were higher and glucose level was lower in cases of NM with
      Gram negatives (p value were respectively, 0.022, 0.039 and 0.049). CONCLUSION:
      As conclusions; in NM, Gram-negative pathogens were seen more frequently;
      A.baumanni was the predominant pathogen; and NM caused by Gram negatives had
      worse clinical and laboratory characteristic and prognostic outcome than Gram
      positives.

PMID- 28758187
TI  - Differences between patients' and clinicians' research priorities from the
      Anaesthesia and Peri-operative Care Priority Setting Partnership.
AB  - The James Lind Alliance Anaesthesia and Peri-operative Care Priority Setting
      Partnership was a recent collaborative venture bringing approximately 2000
      patients, carers and clinicians together to agree priorities for future research
      into anaesthesia and critical care. This secondary analysis compares the research
      priorities of 303 service users, 1068 clinicians and 325 clinicians with
      experience as service users. All three groups prioritised research to improve
      patient safety. Service users prioritised research about improving patient
      experience, whereas clinicians prioritised research about clinical effectiveness.
      Clinicians who had experience as service users consistently prioritised research
      more like clinicians than like service users. Individual research questions about
      patient experience were more popular with patients and carers than with
      clinicians in all but one case. We conclude that patients, carers and clinicians
      prioritise research questions differently. All groups prioritise research into
      patient safety, but service users also favour research into patient experience,
      whereas clinicians favour research into clinical effectiveness.

PMID- 28758188
TI  - A Systematic Review and Meta-Analysis of The Effect of Low Vitamin D on
      Cognition.
AB  - BACKGROUND/OBJECTIVE: With an aging population and no cure for dementia on the
      horizon, risk factor modification prior to disease onset is an urgent health
      priority. Therefore, this review examined the effect of low vitamin D status or
      vitamin D supplementation on cognition in midlife and older adults without a
      diagnosis of dementia. DESIGN: Systematic review and random effect meta-analysis.
      SETTING: Observational (cross-sectional and longitudinal cohort) studies
      comparing low and high vitamin D status and interventions comparing vitamin D
      supplementation with a control group were included in the review and meta
      analysis. PARTICIPANTS: Studies including adults and older adults without a
      dementia diagnosis were included. MEASUREMENTS: Medline (PubMed), AMED, Psych
      INFO, and Cochrane Central databases were searched for articles until August
      2016. The Newcastle-Ottawa Scale and Physiotherapy Evidence Database assessed
      methodological quality of all studies. RESULTS: Twenty-six observational and
      three intervention studies (n = 19-9,556) were included in the meta-analysis. Low
      vitamin D was associated with worse cognitive performance (OR = 1.24, CI = 1.14
      1.35) and cognitive decline (OR = 1.26, CI = 1.09-1.23); with cross-sectional
      yielding a stronger effect compared to longitudinal studies. Vitamin D
      supplementation showed no significant benefit on cognition compared with control
      (SMD = 0.21, CI = -0.05 to 0.46). CONCLUSION: Observational evidence demonstrates
      low vitamin D is related to poorer cognition; however, interventional studies are
      yet to show a clear benefit from vitamin D supplementation. From the evidence to
      date, there is likely a therapeutic age window relevant to the development of
      disease and therefore vitamin D therapy. Longitudinal lifespan studies are
      necessary to depict the optimal timing and duration in which repletion of vitamin
      D may protect against cognitive decline and dementia in aging, to better inform
      trials and practice towards a successful therapy.

PMID- 28758189
TI  - Task-oriented interventions for children with developmental co-ordination
      disorder.
AB  - BACKGROUND: Developmental co-ordination disorder (DCD) is a common childhood
      disorder, which can persist into adolescence and adulthood. Children with DCD
      have difficulties in performing the essential motor tasks required for self-care,
      academic, social and recreational activities. OBJECTIVES: To assess the
      effectiveness of task-oriented interventions on movement performance,
      psychosocial functions, activity, and participation for children with DCD and to
      examine differential intervention effects as a factor of age, sex, severity of
      DCD, intervention intensity, and type of intervention. SEARCH METHODS: In March
      2017, we searched the Cochrane Central Register of Controlled Trials (CENTRAL),
      MEDLINE, Embase, 13 other databases, and five trials registers. We also searched
      reference lists, and contacted members of the mailing list of the International
      Conference on DCD to identify additional studies. SELECTION CRITERIA: We included
      all randomised controlled trials (RCTs) and quasi-RCTs that compared the task
      oriented intervention with either an inactive control intervention or an active
      control intervention in children and adolescents aged four to 18 years with a
      diagnosis of DCD.Types of outcome measures included changes in motor function, as
      assessed by standardised performance outcome tests and questionnaires; adverse
      events; and measures of participation. DATA COLLECTION AND ANALYSIS: All review
      authors participated in study selection, data extraction, and assessments of risk
      of bias and quality, and two review authors independently performed all tasks.
      Specifically, two review authors independently screened titles and abstracts to
      eliminate irrelevant studies, extracted data from the included studies, assessed
      risk of bias, and rated the quality of the evidence using the GRADE approach. In
      cases of ambiguity or information missing from the paper, one review author
      contacted trial authors. MAIN RESULTS: This review included 15 studies (eight
      RCTs and seven quasi-RCTs). Study characteristicsThe trials included 649
      participants of both sexes, ranging in age from five to 12 years.The participants
      were from Australia, Canada, China, Sweden, Taiwan, and the UK.Trials were
      conducted in hospital settings; at a university-based clinic, laboratory, or
      centre; in community centres; at home or school, or both at home and school.The
      durations of task-oriented interventions were mostly short term (less than six
      months), with the total number of sessions ranging from five to 50. The length of
      each session ranged from 30 to 90 minutes, and the frequencies ranged from once
      to seven times per week.We judged the risk of bias as moderate to high across the
      studies. Some elements were impossible to achieve (such as blinding of
      administering personnel or participants). KEY RESULTS: primary outcomesA meta
      analysis of two RCTs and four quasi-RCTs found in favour of task-oriented
      interventions for improved motor performance compared to no intervention (mean
      difference (MD) -3.63, 95% confidence interval (CI) -5.88 to -1.39; P = 0.002; I2
      = 43%; 6 trials, 169 children; very low-quality evidence).A meta-analysis of two
      RCTs found no effect of task-oriented interventions for improved motor
      performance compared to no intervention (MD -2.34, 95% CI -7.50 to 2.83; P =
      0.38; I2 = 42%; 2 trials, 51 children; low-quality evidence).Two studies reported
      no adverse effects or events. Through personal correspondence, the authors of
      nine studies indicated that no injuries had occurred. KEY RESULTS: secondary
      outcomesDue to the limited number of studies with complete and consistent data,
      we were unable to perform any meta-analyses on our secondary measures or any
      subgroup analysis on age, sex, severity of DCD, and intervention intensity.
      AUTHORS' CONCLUSIONS: We have very little confidence in the effect estimate: the
      true effect is likely to be substantially different from the estimate of effect.
      The conclusions drawn from previous reviews, which unanimously reported
      beneficial effects of intervention, are inconsistent with our conclusions. This
      review highlights the need for carefully designed and executed RCTs to
      investigate the effect of interventions for children with DCD.

PMID- 28758190
TI  - Keratoacanthoma management: results of a survey of U.K. dermatologists and
      surgeons.

PMID- 28758192
TI  - Dose-Exposure-Response Relationship of the Investigational Anti-Interleukin-13
      Monoclonal Antibody Tralokinumab in Patients With Severe, Uncontrolled Asthma.
AB  - Interleukin (IL)-13 is involved in the pathogenesis of some types of asthma.
      Tralokinumab is a human immunoglobulin G4 monoclonal antibody that specifically
      binds to IL-13. Two placebo-controlled phase II studies (phase IIa, NCT00873860
      and phase IIb, NCT01402986) have been conducted in which tralokinumab was
      administered subcutaneously. This investigation aimed to characterize
      tralokinumab's dose-exposure-response (forced expiratory volume in 1 s (FEV1 ))
      relationship in patients with asthma and to predict the most appropriate dose for
      phase III. An integrated population pharmacokinetic-pharmacodynamic (PK/PD)
      modeling analysis was required for phase III dose selection, due to differing
      phase II patient populations, designs, and regimens. Analysis of combined
      datasets enabled the identification of tralokinumab's dose-exposure-FEV1 response
      relationship in patients with asthma. Near-maximal FEV1 increase was predicted at
      a dose of 300 mg SC once every 2 weeks (Q2W). This dose was chosen for
      tralokinumab in the phase III clinical development program for treatment of
      severe, uncontrolled asthma.

PMID- 28758191
TI  - Interleukin-27 signalling induces stem cell antigen-1 expression in T lymphocytes
      in vivo.
AB  - Stem cell antigen-1 (Sca-1/Ly6A/E) is a cell surface glycoprotein that is often
      used as a biomarker for stem cells and cell stemness. However, it is not clear
      what factors can directly induce the expression of Sca-1/Ly6A/E in T lymphocytes
      in vivo, and if induction of Sca-1 is associated with T cell stemness. In this
      study, we show that interleukin-27 (IL-27), a member of the IL-12 family of
      cytokines, directly induces Sca-1 expression in T cells in vivo. We found that
      mice-deficient for IL-27 (either P28 or EBI3) or its signalling (IL-27Ralpha) had
      profound reduction of Sca-1 expression in naive (CD62L+  CD44- ), memory (CD62L+ 
      CD44+ ) and effector (CD62L-  CD44+ ) T cells. In contrast, in vivo delivery of
      IL-27 using adeno-associated viral vectors strongly induced the expression of Sca
      1 in naive and memory/effector T-cell populations in an IL-27 receptor- or signal
      transducer and activator of transcription 1-dependent manner. Interestingly, IL
      27-induced Sca-1+ T cells do not express or up-regulate classic stem cell
      associated genes such as Nanog, Oct4, Sox2 and Ctnnb1. However, IL-27-induced Sca
      1+ T cells had increased expression of effector/memory-associated transcription
      factor T-bet, Eomes and Blimp1. Hence, IL-27 signalling directly induces the
      expression of Sca-1/Ly6A/E expression in T cells. Direct expansion of Sca-1+ 
      CD62L+  CD44- T memory stem cells may explain why IL-27 enhances T-cell memory.

PMID- 28758194
TI  - Reply to Moon and Minhas: Teasing apart NAD+ metabolism in inflammation:
      commentary on Zhou et al. (2016). Br J Pharmacol 173: 2352-2368.

PMID- 28758193
TI  - Melanopsin ganglion cell outer retinal dendrites: Morphologically distinct and
      asymmetrically distributed in the mouse retina.
AB  - A small population of retinal ganglion cells expresses the photopigment
      melanopsin and function as autonomous photoreceptors. They encode global
      luminance levels critical for light-mediated non-image forming visual processes
      including circadian rhythms and the pupillary light reflex. There are five
      melanopsin ganglion cell subtypes (M1-M5). M1 and displaced M1 (M1d) cells have
      dendrites that ramify within the outermost layer of the inner plexiform layer. It
      was recently discovered that some melanopsin ganglion cells extend dendrites into
      the outer retina. Outer Retinal Dendrites (ORDs) either ramify within the outer
      plexiform layer (OPL) or the inner nuclear layer, and while present in the mature
      retina, are most abundant postnatally. Anatomical evidence for synaptic
      transmission between cone photoreceptor terminals and ORDs suggests a novel
      photoreceptor to ganglion cell connection in the mammalian retina. While it is
      known that the number of ORDs in the retina is developmentally regulated, little
      is known about the morphology, the cells from which they originate, or their
      spatial distribution throughout the retina. We analyzed the morphology of
      melanopsin-immunopositive ORDs in the OPL at different developmental time points
      in the mouse retina and identified five types of ORDs originating from either M1
      or M1d cells. However, a pattern emerges within these: ORDs from M1d cells are
      generally longer and more highly branched than ORDs from conventional M1 cells.
      Additionally, we found ORDs asymmetrically distributed to the dorsal retina. This
      morphological analysis provides the first step in identifying a potential role
      for biplexiform melanopsin ganglion cell ORDs.

PMID- 28758195
TI  - The impact of traditionality/modernity on identification- and calculus-based
      trust.
AB  - We conducted three studies to explore how trust is perceived, displayed or
      changed by participants in China, which as a country has undergone substantial
      cultural and historical transition. Traditionality showed a significant positive
      correlation with identification-based trust (IBT) and modernity was significantly
      associated with calculus-based trust (CBT; Study 1). Compared to those primed
      with modern Chinese culture stimuli, participants primed with traditional icons
      exhibited a higher level of IBT and a lower level of CBT (Study 2). The study
      further demonstrated more trust behaviour based on identification with
      traditional culture priming and more trust behaviour based on calculus when
      primed with modern culture (Study 3). In sum, the present findings suggest that,
      along with substantial social changes and economic development, people exhibit
      their trust differently depending on cultural context, shedding light on the
      trust crisis in contemporary China.

PMID- 28758196
TI  - Influence of predation on community resilience to disease.
AB  - Outbreaks of generalist pathogens are influenced by host community structure,
      including population density and species diversity. Within host communities
      predation can influence pathogen transmission rates, prevalence and impacts.
      However, the influence of predation on community resilience to outbreaks of
      generalist pathogens is not fully understood. The role of predation on host
      community resilience to disease was assessed using an epidemiological multi-host
      susceptible-exposed-infectious-recovered model. Sphaerothecum destruens, an
      emerging fungal-like generalist pathogen, was used as a model pathogen. Six
      cyprinid and salmonid fishes, including an asymptomatic carrier, were selected as
      model hosts that are known to be impacted by S. destruens, and they were used
      within a model host community. Pathogen release into the host community was via
      introduction of the asymptomatic carrier. Mortality from infection, pathogen
      incubation rate, and host recovery rate were set to a range of evidence-based
      values in each species and were varied in secondary consumers to predict top-down
      effects of infection on the resilience of a host community. Predation pressure
      within the fish community was varied to test its effects on infection prevalence
      and host survival in the community. Model predictions suggested that predation of
      the asymptomatic hosts by fishes in the host community was insufficient to
      eliminate S. destruens. Sphaerothecum destruens persisted in the community due to
      its rapid transmission from the asymptomatic host to susceptible host fishes.
      Following transmission, pathogen prevalence in the community was driven by
      transmission within and between susceptible host fishes, indicating low host
      community resilience. However, introducing low densities of a highly specific
      piscivorous fish into the community to pre-date asymptomatic hosts could limit
      pathogen prevalence in the host community, thus increasing resilience. The model
      predictions indicate that whilst resilience to this generalist pathogen in the
      host community was low, this could be increased using management interventions.
      The results suggest that this model has high utility for predicting community
      resilience to disease and thus can be applied to other generalist parasites to
      determine risks of disease emergence.

PMID- 28758197
TI  - Enhanced immune-modulatory effects of thalidomide and dexamethasone co-treatment
      on T cell subsets.
AB  - Thalidomide (TM) has been reported to have anti-cancer and anti-inflammatory
      properties, and dexamethasone (DX) is known to reduce inflammation and inhibit
      production of inflammatory cytokines. Many studies have reported that
      combinatorial therapy with TM and DX is clinically used to treat multiple myeloma
      and lupus nephritis, but the mechanism responsible for its effects has not been
      elucidated. In this study, we determined that TM and DX co-treatment had an
      enhanced immune-modulatory effect on T cells through regulating the expression of
      co-stimulatory molecules. Splenic naive T cells from C57BL/6 mice were sort
      purified and cultured for CD4+ T cell proliferation and regulatory T (Treg) cell
      conversion in the presence of TM and/or DX. Following incubation with the drugs,
      cells were collected and OX40, 4-1BB, and glucocorticoid-induced tumour necrosis
      factor receptor-related protein (GITR) expression was quantified by flow
      cytometry. TM (1 or 10 MUm) decreased CD4+ T cell proliferation in a dose
      dependent manner, whereas TM/DX (0.1 or 1 nm) co-treatment further decreased
      proliferation. Treg cell populations were preserved following drug treatment.
      Furthermore, expression of co-stimulatory molecules decreased upon TM/DX co
      treatment in effector T (Teff) cells and was preserved in Treg cells. Splenic
      CD4+ T cells isolated from TM- and DX-treated mice exhibited the same patterns of
      Teff and Treg cell populations as observed in vitro. Considering the selective
      effect of TM on different T cell subsets, we suggest that TM may play an
      immunomodulatory role and that TM/DX combinatorial treatment could further
      enhance these immunomodulatory effects by regulating GITR, OX40, and 4-1BB
      expression in CD4+ T cells.

PMID- 28758198
TI  - MiR-15a/16 deficiency enhances anti-tumor immunity of glioma-infiltrating CD8+ T
      cells through targeting mTOR.
AB  - MiR-15a/16, a miRNA cluster located at chromosome 13q14, has been reported to act
      as an immune regulator in inflammatory disorders besides its aberrant expression
      in cancers. However, little is known about its regulation in tumor-infiltrating
      immune cells. In our study, using an orthotropic GL261 mouse glioma model, we
      found that miR-15a/16 deficiency in host inhibited tumor growth and prolonged
      mice survival, which might be associated with the accumulation of tumor
      infiltrating CD8+ T cells. More importantly, tumor-infiltrating CD8+ T cells
      without miR-15a/16 showed lower expression of PD-1, Tim-3 and LAG-3, and stronger
      secretion of IFN-gamma, IL-2 and TNF-alpha than WT tumor-infiltrating CD8+ T
      cells. Also, our in vitro experiments further confirmed that miR-15a/16-/- CD8+ T
      displayed higher active phenotypes, more cytokines secretion and faster
      expansion, compared to WT CD8+ T cells. Mechanismly, mTOR was identified as a
      target gene of miR-15a/16 to negatively regulate the activation of CD8+ T cells.
      Taken together, these data suggest that miR-15a/16 deficiency resists the
      exhaustion and maintains the activation of glioma-infiltrating CD8+ T cells to
      alleviate glioma progression via targeting mTOR. Our findings provide evidence
      for the potential immunotherapy through targeting miR-15a/16 in tumor
      infiltrating immune cells.

PMID- 28758199
TI  - Point-of-care measurement of fetal blood lactate - Time to trust a new device.
AB  - BACKGROUND: Point-of-care lactate devices are used worldwide for intrapartum
      decision making. Current practice is often based on Lactate Pro (Arkray) but its
      imminent product discontinuation necessitates determination of an optimal
      replacement device. AIMS: To evaluate the performance of Lactate Pro and two
      other point-of-care devices, Lactate Pro 2 (Arkray) and StatStrip (Nova
      Biomedical), and to derive scalp lactate cut-offs equivalent to the current
      intervention trigger of >4.8 mmol/L. MATERIALS AND METHODS: Paired umbilical cord
      arterial and venous blood samples from 109 births were tested on the three point
      of-care products (two devices each), cross-compared with the reference method
      blood gas analyser. RESULTS: All brands deviate from the blood gas analyser, with
      Lactate Pro and StatStrip results consistently lower and Lactate Pro 2
      consistently higher. Standard deviation from the blood gas analyser was smallest
      for StatStrip (0.78 mmol/L, cord artery), and largest for Lactate Pro 2 (1.03
      mmol/L, cord artery). Within-brand variation exists and is similar for all brands
      (mean absolute difference on cord artery 0.23-0.30 mmol/L). Equivalent values to
      the 4.8 mmol/L intervention threshold based on Lactate Pro are 4.9-5.0 mmol/L for
      StatStrip and 5.3-5.9 mmol/L for Lactate Pro 2, calculated by receiver-operating
      characteristic analysis. CONCLUSIONS: StatStrip appears superior to Lactate Pro 2
      to replace the original Lactate Pro. Using StatStrip, the 4.8 mmol/L intervention
      threshold equivalent was 4.9-5.0 mmol/L. The variation in accuracy of point-of
      care lactate devices may exceed the small increments (eg <4.2 mmol/L vs >4.8
      mmol/L) that guide obstetric decisions.

PMID- 28758200
TI  - Endoscopic screening for synchronous esophageal neoplasia among patients with
      incident head and neck cancer: Prevalence, risk factors, and outcomes.
AB  - Esophageal squamous-cell neoplasia (ESCN) is a common second primary neoplasia
      found in patients with head-and-neck squamous-cell carcinoma (HNSCC). This study
      sought to identify the risk factors for synchronous ESCN and how they influence
      survival in HNSCC patient. Eight hundred and fifteen incident HNSCC patients were
      prospectively recruited for endoscopy screening for ESCN using white-light
      imaging, narrow-band imaging, Lugol chromoendoscopy, and pathological
      confirmation. Associated lifestyle and clinicopathological data were collected.
      The interquartile follow-up period cutoffs were 11.3, 20.5 and 34.9 months. 124
      patients (15.2%) were diagnosed as having synchronous ESCN (66 low-grade
      dysplasia, 29 high-grade dysplasia, and 29 esophageal squamous-cell carcinoma).
      Consumption of alcohol, but not betel nut or cigarette, was significantly
      associated with the presence of synchronous ESCN (adjusted odds ratio [aOR] = 7.1
      and 10.9 for former and current drinkers, respectively). There was an interaction
      between cumulative dose of alcohol consumption and alcohol flushing response on
      the development of ESCN. High-dose drinkers with flush response were 16.9 times
      more likely to have esophageal high-grade dysplasia/SCC than non-drinkers.
      Compared with oral cavity cancer patients, those with hypopharyngeal, laryngeal
      and oropharyngeal cancer were 6.8, 4.6 and 2.8 times more likely to have
      esophageal high-grade dysplasia/SCC. HNSCC patients with synchronous ESCN had
      lower overall survival than those without (p < 0.0001). In conclusion,
      surveillance of ESCN is strongly recommended for the high-risk subpopulation of
      HNSCC patients, especially drinkers who have a flush response to alcohol, and
      those with distant metastasis of index cancer and cancers in hypopharynx,
      oropharynx and larynx.

PMID- 28758201
TI  - Dental students' attitudes towards management of pain and anxiety during a dental
      emergency: educational issues.
AB  - INTRODUCTION: High levels of patients' pain and anxiety characterise dental
      emergencies. The main objective of this study was to examine the self-reported
      attitudes of dental students towards these parameters in emergency conditions. A
      secondary objective was to determine if individual parameters (gender, personal
      experience of dental pain, personal dental anxiety and year of study) might
      affect their attitudes. METHODS: One-hundred and eighty-seven undergraduate
      dental students with clinical practice completed a multiple-choice self
      administered questionnaire online. The aforesaid individual parameters were
      collected and the students were asked to rate the frequency of their behaviour
      towards items representing good management of patients' pain and anxiety. The chi
      square test of independence, Fisher's exact test and multiple logistic regression
      models were used for statistical analysis. RESULTS: Oral assessment of anxiety
      before treatment was scarce and was significantly associated with the students
      having personally experienced dental pain (P = 0.007). Pre-, intra- and
      postoperative pain appeared to be managed unequally by the students. Male
      students were significantly less likely to inform patients about postoperative
      pain (P = 0.014). More clinical experience was associated with less systematic
      consideration for intra-operative pain (P < 0.05). Being dentally anxious showed
      no significant association with higher frequencies of behaviours towards
      patients' pain and anxiety. CONCLUSIONS: These findings highlight the need for
      educational improvement regarding pain and anxiety in emergency conditions,
      especially concerning the assessment methods and continuity in the control of
      pain. Emergency dental care appears to be a very suitable field for contextual
      learning.

PMID- 28758203
TI  - Haloperidol for psychosis-induced aggression or agitation (rapid
      tranquillisation).
AB  - BACKGROUND: Haloperidol used alone is recommended to help calm situations of
      aggression or agitation for people with psychosis. It is widely accessible and
      may be the only antipsychotic medication available in limited-resource areas.
      OBJECTIVES: To examine whether haloperidol alone is an effective treatment for
      psychosis-induced aggression or agitation, wherein clinicians are required to
      intervene to prevent harm to self and others. SEARCH METHODS: We searched the
      Cochrane Schizophrenia Group's Study-Based Register of Trials (26th May 2016).
      This register is compiled by systematic searches of major resources (including
      AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of
      clinical trials) and their monthly updates, handsearches, grey literature, and
      conference proceedings, with no language, date, document type, or publication
      status limitations for inclusion of records into the register. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) involving people exhibiting
      aggression and/or agitation thought to be due to psychosis, allocated rapid use
      of haloperidol alone (by any route), compared with any other treatment. Outcomes
      of interest included tranquillisation or asleep by 30 minutes, repeated need for
      rapid tranquillisation within 24 hours, specific behaviours (threat or injury to
      others/self), adverse effects. We included trials meeting our selection criteria
      and providing useable data. DATA COLLECTION AND ANALYSIS: We independently
      inspected all citations from searches, identified relevant abstracts, and
      independently extracted data from all included studies. For binary data we
      calculated risk ratio (RR), for continuous data we calculated mean difference
      (MD), and for cognitive outcomes we derived standardised mean difference (SMD)
      effect sizes, all with 95% confidence intervals (CI) and using a fixed-effect
      model. We assessed risk of bias for the included studies and used the GRADE
      approach to produce 'Summary of findings' tables which included our pre-specified
      main outcomes of interest. MAIN RESULTS: We found nine new RCTs from the 2016
      update search, giving a total of 41 included studies and 24 comparisons. Few
      studies were undertaken in circumstances that reflect real-world practice, and,
      with notable exceptions, most were small and carried considerable risk of bias.
      Due to the large number of comparisons, we can only present a summary of main
      results.Compared with placebo, more people in the haloperidol group were asleep
      at two hours (2 RCTs, n=220, RR 0.88, 95%CI 0.82 to 0.95, very low-quality
      evidence) and experienced dystonia (2 RCTs, n=207, RR 7.49, 95%CI 0.93 to 60.21,
      very low-quality evidence).Compared with aripiprazole, people in the haloperidol
      group required fewer injections than those in the aripiprazole group (2 RCTs,
      n=473, RR 0.78, 95%CI 0.62 to 0.99, low-quality evidence). More people in the
      haloperidol group experienced dystonia (2 RCTs, n=477, RR 6.63, 95%CI 1.52 to
      28.86, very low-quality evidence).Four trials (n=207) compared haloperidol with
      lorazepam with no significant differences with regard to number of participants
      asleep at one hour (1 RCT, n=60, RR 1.05, 95%CI 0.76 to 1.44, very low-quality of
      evidence) or those requiring additional injections (1 RCT, n=66, RR 1.14, 95%CI
      0.91 to 1.43, very low-quality of evidence).Haloperidol's adverse effects were
      not offset by addition of lorazepam (e.g. dystonia 1 RCT, n=67, RR 8.25, 95%CI
      0.46 to 147.45, very low-quality of evidence).Addition of promethazine was
      investigated in two trials (n=376). More people in the haloperidol group were not
      tranquil or asleep by 20 minutes (1 RCT, n=316, RR 1.60, 95%CI 1.18 to 2.16,
      moderate-quality evidence). Acute dystonia was too common in the haloperidol
      alone group for the trial to continue beyond the interim analysis (1 RCT, n=316,
      RR 19.48, 95%CI 1.14 to 331.92, low-quality evidence). AUTHORS' CONCLUSIONS:
      Additional data from new studies does not alter previous conclusions of this
      review. If no other alternative exists, sole use of intramuscular haloperidol
      could be life-saving. Where additional drugs are available, sole use of
      haloperidol for extreme emergency could be considered unethical. Addition of the
      sedating promethazine has support from better-grade evidence from within
      randomised trials. Use of an alternative antipsychotic drug is only partially
      supported by fragmented and poor-grade evidence. Adding a benzodiazepine to
      haloperidol does not have strong evidence of benefit and carries risk of
      additional harm.After six decades of use for emergency rapid tranquillisation,
      this is still an area in need of good independent trials relevant to real-world
      practice.

PMID- 28758204
TI  - Freud's 'transference': Clinical technique in the 'Rat Man' case and theoretical
      conceptualization compared.
AB  - A considerable gap exists between clinical psychoanalytic concepts and
      psychoanalytic practice. It can be traced back to the early beginnings of
      psychoanalysis and to Freud's own handling of concepts that he had developed
      himself. Focusing on the concept of 'transference' that Freud in several steps
      coined so precisely from his experiences with hysteric patients and especially
      from his understanding of the 'Dora' case, it can be shown that he - seen from
      today - could not fully apply the meaning of his own concept in the later
      treatment of the so-called 'Rat Man'. Freud's 'Original record of the case' is
      used to scrutinize his way of understanding and handling the transference with
      this patient. To a substantial extent transference as well as counter
      transference was rather enacted than understood in this case, partly due to
      Freud's own personal and scientific interests and to his ambitions to use this
      case as a demonstration of his therapeutic approach. In order to show this, it is
      unavoidable to correct several blurry or even misleading passages of Strachey's
      translation. Findings from numerous workshops using 'comparative clinical
      methods' indicate that up till now we analysts - like Freud - have great
      difficulties in applying Freud's incredible insight that "a whole series of
      former psychic experiences comes alive not as the past but as the present
      relationship to the person of the physician" (Freud, 1905c [1901], p. 279/280, my
      translation).

PMID- 28758202
TI  - Sodium channel subtypes are differentially localized to pre- and post-synaptic
      sites in rat hippocampus.
AB  - Voltage-gated Na+ channels (Nav ) modulate neuronal excitability, but the roles
      of the various Nav subtypes in specific neuronal functions such as synaptic
      transmission are unclear. We investigated expression of the three major brain Nav
      subtypes (Nav 1.1, Nav 1.2, Nav 1.6) in area CA1 and dentate gyrus of rat
      hippocampus. Using light and electron microscopy, we found labeling for all three
      Nav subtypes on dendrites, dendritic spines, and axon terminals, but the
      proportion of pre- and post-synaptic labeling for each subtype varied within and
      between subregions of CA1 and dentate gyrus. In the central hilus (CH) of the
      dentate gyrus, Nav 1.1 immunoreactivity was selectively expressed in presynaptic
      profiles, while Nav 1.2 and Nav 1.6 were expressed both pre- and post
      synaptically. In contrast, in the stratum radiatum (SR) of CA1, Nav 1.1, Nav 1.2,
      and Nav 1.6 were selectively expressed in postsynaptic profiles. We next compared
      differences in Nav subtype expression between CH and SR axon terminals and
      between CH and SR dendrites and spines. Nav 1.1 and Nav 1.2 immunoreactivity was
      preferentially localized to CH axon terminals compared to SR, and in SR dendrites
      and spines compared to CH. No differences in Nav 1.6 immunoreactivity were found
      between axon terminals of CH and SR or between dendrites and spines of CH and SR.
      All Nav subtypes in both CH and SR were preferentially associated with asymmetric
      synapses rather than symmetric synapses. These findings indicate selective
      presynaptic and postsynaptic Nav expression in glutamatergic synapses of CH and
      SR supporting neurotransmitter release and synaptic plasticity.

PMID- 28758206
TI  - The Idiopathic Intracranial Hypertension Treatment Trial: A Review of the
      Outcomes.
AB  - OBJECTIVE: The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) was
      the first large, randomized study on the use of acetazolamide and weight loss for
      treatment of idiopathic intracranial hypertension-associated vision loss. The
      multicenter trial also examined a number of secondary outcomes. This review
      summarizes all available results of the study published in the literature since
      2014. BACKGROUND: Prior to the IIHTT, clinicians managed idiopathic intracranial
      hypertension based on data from small, unmasked trials, expert opinion, and
      clinical experience. Due to the lack of empiric evidence, there were no official
      treatment protocols to guide treatment of the disorder. METHODS: We performed a
      PubMed literature search for all articles with data from the IIHTT Study Group.
      After review of each article and any relevant supporting literature, the results
      were compiled into a summary of the literature. RESULTS: The PubMed search
      identified 14 articles with primary and/or secondary outcome data from the IIHTT.
      We summarized the findings for the primary outcome of visual field outcomes in
      the acetazolamide treatment group compared to the placebo group, as well as
      secondary outcomes for the safety and tolerability of acetazolamide,
      cerebrospinal fluid opening pressure, quality of life, fundus photography, and
      optical coherence tomography. While both groups demonstrated improvement on most
      outcomes, acetazolamide had a greater effect even when controlling for its effect
      on weight loss. CONCLUSIONS: As the first large, randomized, prospective trial,
      the IIHTT extensively expanded the available data on idiopathic intracranial
      hypertension treatment. Most importantly, it provided support for the safe use of
      acetazolamide up to 4 g daily with weight loss for effective treatment of mild
      vision loss in IIH, with associated improvements in papilledema, increased
      intracranial pressure, and quality of life.

PMID- 28758205
TI  - Clustered organization and region-specific identities of estrogen-producing
      neurons in the forebrain of Zebra Finches (Taeniopygia guttata).
AB  - A fast, neuromodulatory role for estrogen signaling has been reported in many
      regions of the vertebrate brain. Regional differences in the cellular
      distribution of aromatase (estrogen synthase) in several species suggest that
      mechanisms for neuroestrogen signaling differ between and even within brain
      regions. A more comprehensive understanding of neuroestrogen signaling depends on
      characterizing the cellular identities of neurons that express aromatase. Calcium
      binding proteins such as parvalbumin and calbindin are molecular markers for
      interneuron subtypes, and are co-expressed with aromatase in human temporal
      cortex. Songbirds like the zebra finch have become important models to understand
      the brain synthesis of steroids like estrogens and the implications for
      neurobiology and behavior. Here, we investigated the regional differences in
      cytoarchitecture and cellular identities of aromatase-expressing neurons in the
      auditory and sensorimotor forebrain of zebra finches. Aromatase was co-expressed
      with parvalbumin in the caudomedial nidopallium (NCM) and HVC shelf (proper name)
      but not in the caudolateral nidopallium (NCL) or hippocampus. By contrast,
      calbindin was not co-expressed with aromatase in any region investigated.
      Notably, aromatase-expressing neurons were found in dense somato-somatic
      clusters, suggesting a coordinated release of local neuroestrogens from clustered
      neurons. Aromatase clusters were also more abundant and tightly packed in the NCM
      of males as compared to females. Overall, this study provides new insights into
      neuroestrogen regulation at the network level, and extends previous findings from
      human cortex by identifying a subset of aromatase neurons as putative inhibitory
      interneurons.

PMID- 28758207
TI  - The potential of computer vision, optical backscattering parameters and
      artificial neural network modelling in monitoring the shrinkage of sweet potato
      (Ipomoea batatas L.) during drying.
AB  - BACKGROUND: Drying is a method used to preserve agricultural crops. During the
      drying of products with high moisture content, structural changes in shape,
      volume, area, density and porosity occur. These changes could affect the final
      quality of dried product and also the effective design of drying equipment.
      Therefore, this study investigated a novel approach in monitoring and predicting
      the shrinkage of sweet potato during drying. Drying experiments were conducted at
      temperatures of 50-70  degrees C and samples thicknesses of 2-6 mm. The volume
      and surface area obtained from camera vision, and the perimeter and illuminated
      area from backscattered optical images were analysed and used to evaluate the
      shrinkage of sweet potato during drying. RESULTS: The relationship between
      dimensionless moisture content and shrinkage of sweet potato in terms of volume,
      surface area, perimeter and illuminated area was found to be linearly correlated.
      The results also demonstrated that the shrinkage of sweet potato based on
      computer vision and backscattered optical parameters is affected by the product
      thickness, drying temperature and drying time. A multilayer perceptron (MLP)
      artificial neural network with input layer containing three cells, two hidden
      layers (18 neurons), and five cells for output layer, was used to develop a model
      that can monitor, control and predict the shrinkage parameters and moisture
      content of sweet potato slices under different drying conditions. The developed
      ANN model satisfactorily predicted the shrinkage and dimensionless moisture
      content of sweet potato with correlation coefficient greater than 0.95.
      CONCLUSION: Combined computer vision, laser light backscattering imaging and
      artificial neural network can be used as a non-destructive, rapid and easily
      adaptable technique for in-line monitoring, predicting and controlling the
      shrinkage and moisture changes of food and agricultural crops during drying. (c)
      2017 Society of Chemical Industry.

PMID- 28758208
TI  - A comparison of the proximate, fibre, mineral content, amino acid and the fatty
      acid profile of Marula (Sclerocarya birrea caffra) nut and soyabean (Glycine max)
      meals.
AB  - BACKGROUND: As a result of shortages and the cost of the currently utilized
      conventional dietary protein sources in the Sub-Saharan Africa feed industry, the
      chemical evaluation of available non-conventional sources for feed is imperative.
      One such source is Marula nut meal (a by-product of Marula oil extraction). The
      present study chemically characterized the nutritional composition of two
      differently processed Marula nut meals (MNMs) and compared them with that of
      solvent extracted soyabean meal (SBM). RESULTS: The MNMs had higher dry matter,
      ether extract and gross energy but lower crude protein and ash contents compared
      to SBM. The cold press produced Marula nut meal (MNM2) had higher arginine than
      the hydraulic filter press produced Marula nut meal (MNM1) and SBM. The meals had
      similar neutral and acid detergent fibre contents. The MNMs had higher
      phosphorus, magnesium and copper concentrations than SBM. Although the total
      saturated fatty acid proportion was similar across the meals, total
      monounsaturated and polyunsaturated fatty acid proportions were higher in MNMs
      and SBM, respectively. Oleic acid was higher in MNMs than in SBM. CONCLUSION: The
      low crude protein content in MNMs compared to SBM is comparable with other
      conventional dietary protein sources. Thus, the MNMs could be used as protein and
      energy feed ingredients. (c) 2017 Society of Chemical Industry.

PMID- 28758210
TI  - Choosing among multiple alternatives: Relative and overall reinforcer rates.
AB  - Choice behavior among two alternatives has been widely researched, but fewer
      studies have examined the effect of multiple (more than two) alternatives on
      choice. Two experiments investigated whether changing the overall reinforcer rate
      affected preference among three and four concurrently scheduled alternatives.
      Experiment 1 trained six pigeons on concurrent schedules with three alternatives
      available simultaneously. These alternatives arranged reinforcers in a ratio of
      9:3:1 with the configuration counterbalanced across pigeons. The overall rate of
      reinforcement was varied across conditions. Preference between the pair of keys
      arranging the 9:3 reinforcer ratio was less extreme than the pair arranging the
      3:1 reinforcer ratio regardless of overall reinforcer rate. This difference was
      attributable to the richer alternative receiving fewer responses per reinforcer
      than the other alternatives. Experiment 2 trained pigeons on concurrent schedules
      with four alternatives available simultaneously. These alternatives arranged
      reinforcers in a ratio of 8:4:2:1, and the overall reinforcer rate was varied.
      Next, two of the alternatives were put into extinction and the random interval
      duration was changed from 60 s to 5 s. The ratio of absolute response rates was
      independent of interval length across all conditions. In both experiments, an
      analysis of sequences of visits following each reinforcer showed that the pigeons
      typically made their first response to the richer alternative irrespective of
      which alternative was just reinforced. Performance on these three- and four
      alternative concurrent schedules is not easily extrapolated from corresponding
      research using two-alternative concurrent schedules.

PMID- 28758211
TI  - Cytomegalovirus viral load in cord blood and impact of congenital infection on
      markers of hematopoietic progenitor cell potency.
AB  - BACKGROUND: The low incidence of cytomegalovirus (CMV) infection in neonates
      decreases the risk of viral transmission with cord blood transplantation. Cord
      blood donors are screened by testing the maternal sample for total antibodies to
      CMV. Some cord blood banks also screen cord blood for CMV-DNA. The aim of this
      study was to develop and validate a multiplex real-time polymerase chain reaction
      assay to measure CMV viral load in cord blood from asymptomatic infants with
      congenital CMV infection and to assess the impact of CMV infection on cord blood
      hematopoietic progenitor cell concentrations and colony-forming unit
      functionality. STUDY DESIGN AND METHODS: CMV infection was evaluated in two
      groups of cord blood donors: 1) 30,308 neonates prospectively screened by saliva
      culture, including 41 positive cases (0.14%), all from mothers with total
      antibodies to CMV; and 2) 4712 newborns from mothers with total antibodies to CMV
      who were screened retrospectively by polymerase chain reaction, including 18
      positive cases (0.38%). All 59 infants with CMV were asymptomatic at birth.
      RESULTS: Among the 59 positive cases, the average CMV viral load in cord blood
      was 20.6 * 104 viral copies (vc)/mL; seven of 59 mothers (12%) had CMV-DNA
      detected, however, with no association to their newborns' CMV viral load. Levels
      of colony-forming units, CD34+ /CD45+ cells, and total nucleated cells measured
      in a cohort of CMV-positive cord blood samples were higher than those in the
      matched control group. CONCLUSION: We developed and validated a multiplex real
      time polymerase chain reaction assay to detect CMV-DNA in cord blood. In our
      study, maternal total antibodies to CMV or CMV-DNA at birth were poor predictors
      of infection in cord blood donors. Furthermore, our results suggest that CMV
      congenital infection impacts CD34+ /CD45+ cells and some hematopoietic progenitor
      cells toward higher proliferation.

PMID- 28758212
TI  - Multichannel wide-field microscopic FRET imaging based on simultaneous spectral
      unmixing of excitation and emission spectra.
AB  - Simultaneous spectral unmixing of excitation and emission spectra (ExEm unmixing)
      has inherent ability resolving spectral crosstalks, two key issues of
      quantitative fluorescence resonance energy transfer (FRET) measurement, of both
      the excitation and emission spectra between donor and acceptor without additional
      corrections. We here set up a filter-based multichannel wide-field microscope for
      ExEm unmixing-based FRET imaging (m-ExEm-spFRET) containing a constant system
      correction factor (fsc ) for a stable system. We performed m-ExEm-spFRET with
      four- and two-wavelength excitation respectively on our system to quantitatively
      image single living cells expressing FRET tandem constructs, and obtained
      accurate FRET efficiency (E) and concentration ratio of acceptor to donor (RC ).
      We also performed m-ExEm-spFRET imaging for single living cells coexpressing CFP
      Bax and YFP-Bax, and found that the E values were about 0 for control cells and
      about 28% for staurosporin-treated cells when RC were larger than 1, indicating
      that staurosporin induced significant oligomerisation.

PMID- 28758209
TI  - Distinct projection targets define subpopulations of mouse brainstem vagal
      neurons that express the autism-associated MET receptor tyrosine kinase.
AB  - Detailed anatomical tracing and mapping of the viscerotopic organization of the
      vagal motor nuclei has provided insight into autonomic function in health and
      disease. To further define specific cellular identities, we paired information
      based on visceral connectivity with a cell-type specific marker of a
      subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and
      nucleus ambiguus (nAmb) that express the autism-associated MET receptor tyrosine
      kinase. As gastrointestinal disturbances are common in children with autism
      spectrum disorder (ASD), we sought to define the relationship between MET
      expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract.
      Using wholemount tissue staining and clearing, or retrograde tracing in a METEGFP
      transgenic mouse, we identify three novel subpopulations of EGFP+ vagal brainstem
      neurons: (a) EGFP+ neurons in the nAmb projecting to the esophagus or laryngeal
      muscles, (b) EGFP+ neurons in the medial DMV projecting to the stomach, and (b)
      EGFP+ neurons in the lateral DMV projecting to the cecum and/or proximal colon.
      Expression of the MET ligand, hepatocyte growth factor (HGF), by tissues
      innervated by vagal motor neurons during fetal development reveal potential sites
      of HGF-MET interaction. Furthermore, similar cellular expression patterns of MET
      in the brainstem of both the mouse and nonhuman primate suggests that MET
      expression at these sites is evolutionarily conserved. Together, the data suggest
      that MET+ neurons in the brainstem vagal motor nuclei are anatomically positioned
      to regulate distinct portions of the gastrointestinal tract, with implications
      for the pathophysiology of gastrointestinal comorbidities of ASD.

PMID- 28758213
TI  - Observations of marine wildlife tourism effects on a non-focal species.
AB  - A radio-acoustic positioning system was used to assess the effects of shark cage
      diving operators (SCDO) on the fine-scale movements of a non-focal species, the
      smooth stingray Bathytoshia brevicaudata. The results revealed that the time
      spent in the array was individually variable, but generally increased when SCDO
      were present and that the presence of SCDO may have the capacity to elicit
      changes in the space use of B. brevicaudata. These results indicate that the
      effects of marine wildlife tourism may extend beyond the focal species of
      interest.

PMID- 28758214
TI  - In vitro methane and gas production with inocula from cows and goats fed an
      identical diet.
AB  - BACKGROUND: Fermentative capacity among ruminants can differ depending on the
      type of ruminant species and the substrate fermented. The aim was to compare in
      vitro cow and goat rumen inocula in terms of methane (CH4 ) and gas production
      (GP), fermentation kinetics and 72 h volatile fatty acids (VFA) production using
      the browse species Acacia etbaica, Capparis tomentosa, Dichrostachys cinerea,
      Rhus natalensis, freeze-dried maize silage and grass silage, and a concentrate as
      substrates. RESULTS: Total GP, CH4 and VFA were higher (P <= 0.008) in goat
      inoculum than cows across substrates. The half-time for asymptotic GP was lower
      (P < 0.0001) in phase 1 and higher (P < 0.012) in phase 2, and the maximum rate
      of GP was higher (P < 0.0001) in phase 1 and phase 3 (P < 0.0001) in goats
      compared to cows. Methane production and as a percentage of total GP was higher
      (P < 0.0001) and the half-time tended (P = 0.059) to be at a later time for goats
      compared to cows. CONCLUSION: Goat inoculum showed higher fermentative activity
      with a concomitant higher CH4 production compared to cows. This difference
      highlights the ability of goats to better utilise browse species and other
      roughage types. (c) 2017 Society of Chemical Industry.

PMID- 28758215
TI  - Application of new insoluble dietary fibres from triticale as supplement in
      yoghurt - effects on physico-chemical, rheological and quality properties.
AB  - BACKGROUND: The need to increase the daily intake of dietary fibres opens a new
      chapter in the research of functional foods enriched with fibres. The potential
      application of an innovative product - insoluble dietary fibres from triticale in
      yoghurts - was deployed by characterising their food application and evaluating
      physico-chemical, rheological and sensory properties and was the aim of this
      research. RESULTS: Detailed characterisations of these fibres are presented for
      the first time and showed very good hydration properties, optimal pH (slightly
      acidic), optimal chemical composition, high antioxidant capacity which was proven
      by phenolics contents. Besides, these fibres showed negligible calorific value,
      with no phytates and high antioxidant capacity, mainly from ferulic acid.
      Therefore they could be successfully added to yoghurt. Enrichment of yoghurt
      having different milk fat content (1.5 and 2.8% w/w) with triticale insoluble
      fibre (1.5% and 3.0% w/w) significantly influenced the syneresis level, its
      apparent viscosity, yield stress and thixotropic behaviour. The overall sensory
      quality scores indicated that yoghurt enriched with 1.5% triticale insoluble
      fibres was recognised as 'excellent' and had enhanced antioxidant activity.
      CONCLUSIONS: Insoluble triticale fibre could therefore be used as a supplement to
      produce functional yoghurt. (c) 2017 Society of Chemical Industry.

PMID- 28758216
TI  - On comparing 2 correlated C indices with censored survival data.
AB  - As new biomarkers and risk prediction procedures are in rapid development, it is
      of great interest to develop valid methods for comparing predictive power of 2
      biomarkers or risk score systems. Harrell C statistic has been routinely used as
      a global adequacy assessment of a risk score system, and the difference of 2
      Harrell C statistics as a test statistic has been suggested in recent literature
      for comparison of predictive power of 2 biomarkers for censored outcome. In this
      study, we showed that such a test can have severely inflated type I errors as the
      difference between the 2 Harrell C statistics does not converge to zero under the
      null hypothesis of equal predictive power measured by concordance probabilities,
      as illustrated by 2 counterexamples and corresponding numerical simulations. We
      further investigate a necessary and sufficient condition under which the
      difference of 2 Harrell C statistics converges to zero under the null hypothesis.

PMID- 28758217
TI  - Being a good or a just teacher: Which experiences of teachers' behavior can be
      more predictive of school bullying?
AB  - In two cross-sectional questionnaire studies with N = 2,931 German students, aged
      between 12 and 17 years (M = 14.1, SD = 0.5), we investigated the relation
      between students' bullying behavior and their personal belief in a just world
      (BJW). We considered students' personal experience of teacher justice as a
      possible mediator in this relation and investigated whether the students'
      experiences of their teachers' classroom management explained bullying behavior
      in addition to personal BJW and teacher justice, while statistically controlling
      for sex and school type. In both studies, multilevel modeling results showed that
      the more students endorsed personal BJW and the more they evaluated their
      teachers' behavior toward them personally as being just, the less likely they
      were to report that they bullied others. The students' personal experience of
      teacher justice mediated the association of personal BJW with bullying.
      Furthermore, the students' personal experience of classroom management
      significantly predicted bullying in addition to personal BJW and teacher justice.
      The observed relations were mainly significant at the individual level. The
      pattern of results persisted when we controlled for school type and when we
      considered student sex as a moderator. We discussed the adaptive functions of BJW
      and implications for future school research and practice.

PMID- 28758218
TI  - Trade associations and labor organizations as intermediaries for disseminating
      workplace safety and health information.
AB  - BACKGROUND: There has not been a systematic study of the nature and extent to
      which business and professional trade associations and labor organizations obtain
      and communicate workplace safety and health information to their members. These
      organizations can serve as important intermediaries and play a central role in
      transferring this information to their members. METHODS: A sample of 2294
      business and professional trade associations and labor organizations in eight
      industrial sectors identified by the National Occupational Research Agenda was
      surveyed via telephone. RESULTS: A small percent of these organizations (40.9% of
      labor organizations, 15.6% of business associations, and 9.6% of professional
      associations) were shown to distribute workplace safety and health information to
      their members. Large differences were also observed between industrial sectors
      with construction having the highest total percent of organizations disseminating
      workplace safety and health information. CONCLUSION: There appears to be
      significant potential to utilize trade and labor organizations as intermediaries
      for transferring workplace safety and health information to their members.
      Government agencies have a unique opportunity to partner with these organizations
      and to utilize their existing communication channels to address high risk
      workplace safety and health concerns.

PMID- 28758219
TI  - Plerocercoids of the cestode Diphyllobothrium ditremum in brown trout Salmo
      trutta: substantial increase in infection after establishment of European minnow
      Phoxinus phoxinus.
AB  - This study focuses on plerocercoids of the cestode Diphyllobothrium ditremum in
      brown trout Salmo trutta from the subalpine lake Ovre Heimdalsvatn in south
      central Norway. Salmo trutta was the only fish species in this lake until
      European minnow Phoxinus phoxinus was registered in 1969. The P. phoxinus
      population increased substantially in the following years. In contrast with the
      1969-1972 period, when plerocercoids of D. ditremum were practically absent in S.
      trutta, there was a high prevalence and intensity of infection in the 2013 S.
      trutta samples. Because the life cycle of D. ditremum involves two larval stages,
      in copepods and salmonids and mature worms in piscivorous birds, such as
      mergansers and loons, a change in feeding ecology of S. trutta or changes in
      population densities of copepods, fish or birds might have influenced the
      infection pattern. No relationships between D. ditremum infection and muscle
      tissue delta15 N signature or Hg concentration were found, indicating that
      infection is not a result of piscivory or cannibalism. Furthermore, consumption
      of copepods by S. trutta during summer and autumn was low. On the other hand, the
      number of piscivorous birds has increased, probably due to the presence of P.
      phoxinus as a new and numerous prey. An increased number of final D. ditremum
      hosts may have produced a higher output of cestode eggs, resulting in more
      infected copepods that in turn are consumed by S. trutta. Indirectly, P. phoxinus
      may therefore have caused the observed increased infection in S. trutta and
      thereby imposed further negative effects on S. trutta in high mountain areas.

PMID- 28758221
TI  - Biological, medicinal and toxicological significance of Eucalyptus leaf essential
      oil: a review.
AB  - The genus Eucalyptus L'Heritier comprises about 900 species, of which more than
      300 species contain volatile essential oil in their leaves. About 20 species,
      within these, have a high content of 1,8-cineole (more than 70%), commercially
      used for the production of essential oils in the pharmaceutical and cosmetic
      industries. However, Eucalyptus is extensively planted for pulp, plywood and
      solid wood production, but its leaf aromatic oil has astounding widespread
      biological activities, including antimicrobial, antiseptic, antioxidant,
      chemotherapeutic, respiratory and gastrointestinal disorder treatment, wound
      healing, and insecticidal/insect repellent, herbicidal, acaricidal, nematicidal,
      and perfumes, soap making and grease remover. In the present review, we have made
      an attempt to congregate the biological ingredients of leaf essential oil, leaf
      oil as a natural medicine, and pharmacological and toxicological values of the
      leaf oil of different Eucalyptus species worldwide. (c) 2017 Society of Chemical
      Industry.

PMID- 28758222
TI  - Mitigation of the threat posed to transfusion by donors traveling to Zika
      affected areas: a Canadian risk-based approach.
AB  - BACKGROUND: The recent spread of the Zika virus to the Americas and the
      recognition that it can cause severe disease in the developing fetus has prompted
      the adoption of measures to mitigate the risk that this virus might pose to
      transfusion safety. In nonendemic countries, the risk to transfusion results from
      donors traveling to an endemic region. Canada implemented a 21-day temporary
      deferral for prospective donors who traveled to such regions. We present the
      rationale for this policy, including a quantitative risk assessment supported by
      a Monte Carlo simulation. STUDY DESIGN AND METHODS: The model considered the
      following parameters, each with specified values and ranges: the probability that
      a donor recently returned from a Zika-endemic region, the duration of travel to
      this region, the daily risk of acquiring Zika while in an endemic region, and the
      incubation and viremic periods. We ran the simulation 20 times, each with 10
      million iterations. RESULTS: In the absence of any travel deferral, 32 donors
      (range, 20-46 donors) would be able to donate while still being at risk of
      transmitting Zika, corresponding to a rate of 1:312,500 (range, 1:217,000 to
      1:500,000). None of these donors would be viremic beyond 21 days after returning
      from their travel, with a risk estimated at less than 1:200,000,000. CONCLUSIONS:
      A 21-day temporary travel deferral offers an extremely wide margin of safety for
      the possible transmission of Zika by a donation obtained from someone who
      recently returned from a country where the virus is circulating.

PMID- 28758220
TI  - Distribution and chemical composition of estrogen receptor beta neurons in the
      paraventricular nucleus of the female and male mouse hypothalamus.
AB  - Activation of estrogen receptor beta (ERbeta)-expressing neurons regulates the
      mammalian stress response via the hypothalamic-pituitary-adrenal (HPA) axis.
      These neurons densely populate the paraventricular nucleus of the hypothalamus
      (PVN). Recent research has revealed striking differences between rat and mouse
      PVN cytochemistry, but careful exploration of PVN ERbeta neurons in mice has been
      hindered by a lack of specific ERbeta antisera. Therefore, we used male and
      female transgenic mice expressing EGFP under the control of the mouse ERbeta
      promoter (ERbeta-EGFP) to examine the chemical architecture of PVN ERbeta cells.
      Using immunohistochemistry, we found that 90% of ERbeta-immunoreactivity (-ir)
      colocalized with EGFP. Cellular colocalization of EGFP with neuropeptides,
      transcription modulators, and neuronal tracers was examined throughout the PVN.
      ERbeta-EGFP cells expressed oxytocin more abundantly in the rostral (71 +/- 3%)
      than caudal (33 +/- 8%) PVN. Arginine vasopressin colocalized with EGFP more
      often in females (18 +/- 3%) than males (4 +/- 1%). Moreover, estrogen receptor
      alpha-ir colocalized with ERbeta-EGFP at low levels (15 +/- 3%). Using a
      corticotropin releasing hormone-cre driver X tdTomato reporter mouse, we found a
      moderate colocalization with ERbeta-ir (48 +/- 16%) in the middle PVN. Peripheral
      injection of fluorogold revealed that the rostral PVN ERbeta-EGFP cells are
      neuroendocrine neurons whereas non-neuroendocrine (presumably pre-autonomic)
      ERbeta-EGFP neurons predominated in the posterior PVN. These data demonstrate
      chemoarchitectural differences in ERbeta neurons of the mouse PVN that are
      different from that previously described for the rat, thus, elucidating potential
      neuronal pathways involved in the regulation of the HPA axis in mice.

PMID- 28758223
TI  - Metabonomics profiling of marinated meat in soy sauce during processing.
AB  - BACKGROUND: Marinated meat in soy sauce is one of the most popular traditional
      cured meat products in China. Its taste quality is directly related to primary
      and secondary metabolites. Herein, the change of metabolite composition of
      marinated meat in soy sauce during processing was systematically characterised
      using 1 H NMR and multivariate data analysis. RESULTS: The marinated meat in soy
      sauce metabonome was dominated by 26 metabolites, including amino acids, sugars,
      organic acids, nucleic aides and their derivatives. PC1 and PC2 explained a total
      of 78.6% and 16.6% of variables, respectively. Amino acids, sugars, acetate,
      succinate, uracil and inosine increased during marinating, while lactate,
      creatine, inosine-5'-monophosphate (5'-IMP) and anserine decreased (P < 0.05).
      After marinating, most of the metabolites decreased except for acetate and
      alanine (P < 0.05). There was a negative effect on the taste of marinated meat in
      soy sauce during the late stage of dry-ripening. CONCLUSION: These findings
      indicated that the potential of NMR-based metabonomics is of importance for taste
      quality of marinated meat in soy sauce, which could contribute to a better
      understanding of the changes of taste compounds in meat products during
      processing. Shortening the dry-ripening period could be considered to improve the
      taste quality. (c) 2017 Society of Chemical Industry.

PMID- 28758224
TI  - A method to address between-subject heterogeneity for identification of principal
      surrogate markers in repeated low-dose challenge HIV vaccine studies.
AB  - Repeated low-dose challenge designs in nonhuman primate studies have recently
      received attention in the literature as a means of evaluating vaccines for HIV
      prevention and identifying immune surrogates for their protective effects.
      Existing methods for surrogate identification in this type of study design rely
      on the assumption of homogeneity across subjects (namely, independent infection
      risks after each challenge within each subject and conditional on covariates). In
      practice, random variation across subjects is likely to occur because of
      unmeasured biologic factors. Failure to account for this heterogeneity or within
      subject correlation can result in biased inference regarding the surrogate value
      of immune biomarkers and underpowered study designs for detecting surrogate
      endpoints. In this paper, we adopt a discrete-time survival model with random
      effects to account for between-subject heterogeneity, and we develop estimators
      and testing procedures for evaluating principal surrogacy of immune biomarkers.
      Simulation studies reveal that the heterogeneous model achieves substantial bias
      reduction compared to the homogeneous model, with little cost of efficiency. We
      recommend the use of this heterogeneous model as a complementary tool to existing
      methods when designing and analyzing repeated low-dose challenge studies for
      evaluating surrogate endpoints.

PMID- 28758225
TI  - Metabolism of 7-ethoxycoumarin, flavanone and steroids by cytochrome P450 2C9
      variants.
AB  - CYP2C9 is a human microsomal cytochrome P450c (CYP). Much of the variation in
      CYP2C9 levels and activity can be attributed to polymorphisms of this gene. Wild
      type CYP2C9 and mutants were coexpressed with NADPH-cytochrome P450 reductase in
      Escherichia coli. The hydroxylase activities toward 7-ethoxycoumarin, flavanone
      and steroids were examined. Six CYP2C9 variants showed Soret peaks (450 nm)
      typical of P450 in reduced CO-difference spectra. CYP2C9.38 had the highest 7
      ethoxycoumarin de-ethylase activity. All the CYP2C9 variants showed lower
      flavanone 6-hydroxylation activities than CYP2C9.1 (the wild-type). CYP2C9.38
      showed higher activities in testosterone 6beta-hydroxylation, progesterone 6beta
      /16alpha-hydroxylation, estrone 11alpha-hydroxylation and estradiol 6alpha
      hydroxylation than CYP2C9.1. CYP2C9.40 showed higher testosterone 17-oxidase
      activity than CYP2C9.1; CYP2C9.8 showed higher estrone 16alpha-hydroxylase
      activity and CYP2C9.12 showed higher estrone 11alpha-hydroxylase activity.
      CYP2C9.9 and CYP2C9.10 showed similar activities to CYP2C9.1. These results
      indicate that the substrate specificity of CYP2C9.9 and CYP2C9.10 was not
      changed, but CYP2C9.8, CYP2C9.12 and CYP2C9.40 showed different substrate
      specificity toward steroids compared with CYP2C9.1; and especially CYP2C9.38
      displayed diverse substrate specificities towards 7-ethoxycoumarin and steroids.

PMID- 28758226
TI  - Changes in rheological properties of wheat due to storage.
AB  - BACKGROUND: The present study aimed to investigate changes in the fundamental
      rheological properties of dough prepared from wheat grains stored for 6 months at
      20  degrees C, at ambient temperature (temperature varied with time) and at 4 
      degrees C. Stress/shear rate ramp, oscillation and creep-recovery tests were
      performed to assess the changes in rheological properties as a result of storage.
      RESULTS: Samples were observed to be non-Newtonian; thus, the Bingham model
      estimated the yield stress, which was maximum for the wheat stored under ambient
      conditions and minimum for wheat stored at 20  degrees C. The stress required to
      break the bonds was maximum for wheat-dough stored under ambient conditions and
      minimum for wheat stored at 20  degrees C. Wheat stored at 20  degrees C also had
      the highest maximum creep and recovery strain. The viscoelastic properties of the
      three wheat-dough samples were compared. CONCLUSION: The results obtained in the
      present study show that the wheat-dough prepared under ambient conditions behaves
      as a rigid and stiff material. The dough prepared from wheat stored at 20 
      degrees C had the maximum elasticity. (c) 2017 Society of Chemical Industry.

PMID- 28758227
TI  - Standardization approaches in absolute quantitative proteomics with mass
      spectrometry.
AB  - Mass spectrometry-based approaches have enabled important breakthroughs in
      quantitative proteomics in the last decades. This development is reflected in the
      better quantitative assessment of protein levels as well as to understand post
      translational modifications and protein complexes and networks. Nowadays, the
      focus of quantitative proteomics shifted from the relative determination of
      proteins (ie, differential expression between two or more cellular states) to
      absolute quantity determination, required for a more-thorough characterization of
      biological models and comprehension of the proteome dynamism, as well as for the
      search and validation of novel protein biomarkers. However, the physico-chemical
      environment of the analyte species affects strongly the ionization efficiency in
      most mass spectrometry (MS) types, which thereby require the use of specially
      designed standardization approaches to provide absolute quantifications. Most
      common of such approaches nowadays include (i) the use of stable isotope-labeled
      peptide standards, isotopologues to the target proteotypic peptides expected
      after tryptic digestion of the target protein; (ii) use of stable isotope-labeled
      protein standards to compensate for sample preparation, sample loss, and
      proteolysis steps; (iii) isobaric reagents, which after fragmentation in the
      MS/MS analysis provide a final detectable mass shift, can be used to tag both
      analyte and standard samples; (iv) label-free approaches in which the absolute
      quantitative data are not obtained through the use of any kind of labeling, but
      from computational normalization of the raw data and adequate standards; (v)
      elemental mass spectrometry-based workflows able to provide directly absolute
      quantification of peptides/proteins that contain an ICP-detectable element. A
      critical insight from the Analytical Chemistry perspective of the different
      standardization approaches and their combinations used so far for absolute
      quantitative MS-based (molecular and elemental) proteomics is provided in this
      review.

PMID- 28758228
TI  - The chronic sorrow experiences of caregivers of clients with schizophrenia in
      Taiwan: A phenomenological study.
AB  - PURPOSE: The aim of the article is to explore the chronic sorrow experiences of
      the caregivers of clients with schizophrenia in Taiwan. DESIGN AND METHODS:
      Descriptive, phenomenological, and purposive sampling and one-to-one, in-depth,
      and unstructured interviews were used. Data saturation was achieved after
      interviewing 12 participants. Narratives were analyzed using Colaizzi's (1978)
      method. FINDINGS: Three themes and eight subthemes emerged, including
      encountering sorrow (disordered life, disintegrated self-esteem, little prospect
      for hope, and collapsed sense of security), talking with sorrow (cognitive change
      and transformation of action), and living with sorrow (living with defects and
      living with responsibilities). PRACTICE IMPLICATIONS: Advanced practice
      psychiatric nurses should take the emotional stability of caregivers into
      consideration. Caregivers should be encouraged and taught effective culture
      oriented strategies for living with sorrow.

PMID- 28758229
TI  - Time-dependent factors in DIEP flap breast reconstruction.
AB  - BACKGROUND: The process of harvesting and performing microsurgical anastomosis
      may lengthen deep inferior epigastric artery perforator (DIEP) flap breast
      reconstruction affecting results and patient safety. The aim of the study was to
      investigate the associations between predictors and operative time (OT). METHODS:
      Between 2004 and 2016, 336 immediate and 68 delayed unilateral reconstructions
      were performed in 404 patients. Age, weight, height, body mass index (BMI),
      nulliparity, or pluriparity condition were collected to determine the impact of
      patient characteristics on OT. Flap weight, mastectomy type, flap zone,
      perforator number, venous anastomoses, recipient vessels selection,
      reconstruction timing, contralateral symmetrization, and a dedicated
      anesthesiologist were analyzed as possible predictors. RESULTS: Mean OT was 289
      min (range, 150-550 min). Using univariate analysis, for each increment of BMI
      value and patient weight OT increased, respectively, 3.5- and 1.4 min (97.5% CI:
      1.768-5.145, 97.5% CI: 0.739-1.949; P < 0.001). Skin-sparing mastectomy (SSM)
      (97.5% CI: 2.487-36.637; P = 0.025), perforator number, and venous anastomoses
      (97.5% CI: 24.468-43.690, 97.5% CI: 24.843-50.492; P < 0.001) negatively
      influenced OT while nipple-sparing mastectomy (NSM) reduced OT of 22.7-min (97.5%
      CI: -40.333 to -5.098; P = 0.012). The use of circumflex scapular vessels as
      recipients reduced OT of 75.4-min while internal mammary vessels (IMV) increased
      OT of 55.8-min (97.5% CI: -88.631 to -62.209, 97.5% CI: 22.918-88.642; P <
      0.001). A dedicated anesthesiologist and the learning curve (LC) reduced OT,
      respectively, of 39.63-min and of 13-min for every year (97.5% CI: -57.119 to 
      22.137, 97.5% CI: -14.666 to -11.898; P < 0.001). Using multivariate regression,
      LC was a negative predictor while SSM, perforators number, superficial epigastric
      vein, IMV, and flap weight were positive predictors (P < 0.001). CONCLUSIONS: The
      increase of flap weight, related perforators number, and venous drainage
      negatively influence OT. LC meaning systematic approach for surgery can optimize
      DIEP flap surgery efficiency.

PMID- 28758230
TI  - Eyeballing: the use of visual appearance to diagnose 'sick'.
AB  - CONTEXT: Prior studies suggest that clinicians can categorise patients in an
      emergency room as 'sick' or 'not sick' using rapid visual assessment. The rapid
      nature of these decisions suggests clinicians are relying on pattern recognition
      or System 1 processing; however, this has not been studied experimentally. In
      this study, we explore the accuracy of these decisions using patient disposition
      (discharge, admission to ward or admission to critical care) as an objective
      outcome, and collect evidence to argue for the use of System 1 processing in the
      'sick' or 'not sick' decision process. METHODS: Fourteen practising emergency
      physicians reviewed 25 videos of patients presenting to the emergency room. They
      were asked to predict patient disposition (discharge, admission to ward or
      admission to critical care) and estimate whether they were 'sick' or 'not sick'
      using a continuous slider on a 'sick' scale from 'not sick' (0) to 'sick' (100).
      We collected decision time and asked physicians to identify how they came to the
      decision using a continuous slider on a 'system processing' scale from 'knew
      immediately' (0) to 'deliberated intently' (1). RESULTS: Inter-rater reliability
      judging 'sick' was computed as an intraclass correlation coefficient (ICC) of
      0.54. Agreement among physicians in predicting disposition was 68% with ICC of
      0.44, and accuracy at predicting disposition was 55%. Physicians made their
      decision in an average of 10 - 11 seconds and rated 70% of their decisions as <
      0.5 on the scale from 'knew immediately' (0) to 'deliberated intently' (1).
      CONCLUSIONS: Experienced emergency physicians are able to visually assess
      patients rapidly and predict disposition in a very short time, albeit with fair
      reliability and lower accuracy than reported previously. Subjectively, they
      reported that the majority of decisions were on the side of 'knew immediately',
      consistent with the application of System 1 processing.

PMID- 28758231
TI  - Redefining the stress cortisol response to surgery.
AB  - BACKGROUND: Cortisol levels rise with the physiological stress of surgery.
      Previous studies have used older, less-specific assays, have not differentiated
      by severity or only studied procedures of a defined type. The aim of this study
      was to examine this phenomenon in surgeries of varying severity using a widely
      used cortisol immunoassay. METHODS: Euadrenal patients undergoing elective
      surgery were enrolled prospectively. Serum samples were taken at 8 am on surgical
      day, induction and 1 hour, 2 hour, 4 hour and 8 hour after. Subsequent samples
      were taken daily at 8 am until postoperative day 5 or hospital discharge. Total
      cortisol was measured using an Abbott Architect immunoassay, and cortisol-binding
      globulin (CBG) using a radioimmunoassay. Surgical severity was classified by
      POSSUM operative severity score. RESULTS: Ninety-three patients underwent
      surgery: Major/Major+ (n = 37), Moderate (n = 33) and Minor (n = 23). Peak
      cortisol positively correlated to severity: Major/Major+ median 680 [range 375
      1452], Moderate 581 [270-1009] and Minor 574 [272-1066] nmol/L (Kruskal-Wallis
      test, P = .0031). CBG fell by 23%; the magnitude of the drop positively
      correlated to severity. CONCLUSIONS: The range in baseline and peak cortisol
      response to surgery is wide, and peak cortisol levels are lower than previously
      appreciated. Improvements in surgery, anaesthetic techniques and cortisol assays
      might explain our observed lower peak cortisols. The criteria for the dynamic
      testing of cortisol response may need to be reduced to take account of these
      factors. Our data also support a lower-dose, stratified approach to dosing of
      steroid replacement in hypoadrenal patients, to minimize the deleterious effects
      of over-replacement.

PMID- 28758232
TI  - Administrations of thalidomide into the rostral ventromedial medulla produce
      antinociceptive effects in a rat model of postoperative pain.
AB  - The rostral ventromedial medulla (RVM) is highly involved in pain signal
      transmissions. Previous studies have shown that thalidomide is anti-nociceptive.
      Thus, we evaluated the neurobiological mechanisms of thalidomide in the RVM in
      the regulation of postoperative pain. We used a rat model of postoperative pain
      to investigate the effects of intra-RVM thalidomide treatments on postoperative
      pain, and evaluate the role of cannabinoid receptors in the effects of intra-RVM
      thalidomide treatments on GABAergic neurotransmission in the RVM neurons. We
      found intra-RVM thalidomide treatments reduced incisional surgery induced
      mechanical allodynia. This phenomenon was associated with attenuation of the
      frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs)
      and spontaneous IPSCs (sIPSCs) in RVM neurons. Furthermore, applications of WIN
      55,212-3 mesylate, a non-selective cannabinoid receptor antagonist reversed the
      effects of repeated thalidomide treatment on the frequency but not the amplitude
      of mIPSCs and sIPSCs. Finally, we found that repeated thalidomide treatment
      robustly enhanced CB2 receptor expression, but slightly reduced CB1 receptor
      expression, in the RVM. These results suggested that the antinociceptive effects
      of thalidomide in the RVM likely involve the attenuation of GABA release, which
      are critically regulated by cannabinoid receptors.

PMID- 28758233
TI  - Exploring examinee behaviours as validity evidence for multiple-choice question
      examinations.
AB  - CONTEXT: Clinical-vignette multiple choice question (MCQ) examinations are used
      widely in medical education. Standardised MCQ examinations are used by licensure
      and certification bodies to award credentials that are meant to assure
      stakeholders as to the quality of physicians. Such uses are based on the
      interpretation of MCQ examination performance as giving meaningful information
      about the quality of clinical reasoning. There are several assumptions
      foundational to these interpretations and uses of standardised MCQ examinations.
      This study explores the implicit assumption that cognitive processes elicited by
      clinical-vignette MCQ items are like the processes thought to occur with 'real
      world' clinical reasoning as theorised by dual-process theory. METHODS: Fourteen
      participants (three medical students, five residents and six staff physicians)
      completed three sets of five timed MCQ items (total 15) from the Medical
      Knowledge Self-Assessment Program (MKSAP). Upon answering a set of MCQs, each
      participant completed a retrospective think aloud (TA) protocol. Using constant
      comparative analysis (CCA) methods sensitised by dual-process theory, we
      performed a qualitative thematic analysis. RESULTS: Examinee behaviours fell into
      three categories: clinical reasoning behaviours, test-taking behaviours and
      reactions to the MCQ. Consistent with dual-process theory, statements about
      clinical reasoning behaviours were divided into two sub-categories: analytical
      reasoning and non-analytical reasoning. Each of these categories included several
      themes. CONCLUSIONS: Our study provides some validity evidence that test-takers'
      descriptions of their cognitive processes during completion of high-quality
      clinical-vignette MCQs align with processes expected in real-world clinical
      reasoning. This supports one of the assumptions important for interpretations of
      MCQ examination scores as meaningful measures of clinical reasoning. Our
      observations also suggest that MCQs elicit other cognitive processes, including
      certain test-taking behaviours, that seem 'inauthentic' to real-world clinical
      reasoning. Further research is needed to explore if similar themes arise in other
      contexts (e.g. simulated patient encounters) and how observed behaviours relate
      to performance on MCQ-based assessments.

PMID- 28758234
TI  - Beyond your very eyes: eye movements are necessary, not sufficient.

PMID- 28758235
TI  - Great expectations: An analysis of researchers' and policy makers' perceptions of
      the potential value of the Australian indigenous burden of disease study for
      policy.
AB  - The "Burden of disease and injury in Aboriginal and Torres Strait Islander
      Peoples" was commissioned by the Australian government as part of the Australian
      Burden of Disease study. This paper explores the extent to which key actors in
      the research and policy communities expected the Indigenous Burden of Disease
      study's findings to inform, influence, or drive federal decisions concerning
      Indigenous health in Australia. This qualitative research undertook interviews
      with 13 key informants with significant involvement in the Indigenous Burden of
      Disease study: six researchers, five policy makers, and two knowledge brokers.
      Interviews were recorded, transcribed, and analyzed, and the findings were
      triangulated with a review of the literature. Policy makers and researchers
      anticipated that the Indigenous Burden of Disease study would improve the
      available information for policy deliberations about Indigenous health. Beyond
      that, their expectations about its policy influence differed substantially, with
      researchers more confident of the study's capacity to guide health priorities,
      and policy makers situating findings in the context of other critical inputs.
      Expectations of policy influence are shaped by the disciplinary perspectives of
      actors, and their relationship to policy outcomes and cannot be examined without
      also considering the policy, political, and financing context of the study being
      analyzed.

PMID- 28758236
TI  - Morphometric age and survival following kidney transplantation.
AB  - BACKGROUND: As patients with chronic kidney disease become older, there is
      greater need to identify who will most benefit from kidney transplantation.
      Analytic morphomics has emerged as an objective risk assessment tool distinct
      from chronologic age. We hypothesize that morphometric age is a significant
      predictor of survival following transplantation. METHODS: A retrospective cohort
      of 158 kidney transplant patients from 2005 to 2014 with 1-year preoperative
      imaging was identified. Based on a control population comprising of trauma
      patients and kidney donors, morphometric age was calculated using the validated
      characteristics of psoas area, psoas density, and abdominal aortic calcification.
      The primary outcome was post-transplant survival. RESULTS: Cox regression showed
      morphometric age was a significant predictor of survival (hazard ratio, 1.06 per
      morphometric year [95% confidence interval, 1.03-1.08]; P < .001). Chronological
      age was not significant (hazard ratio, 1.03 per year [0.98-1.07]; P = .22). Among
      the chronologically oldest patients, those with younger morphometric age had
      greater survival rates compared to those with older morphometric age.
      CONCLUSIONS: Morphometric age predicts survival following kidney transplantation.
      Particularly for older patients, it offers improved risk stratification compared
      to chronologic age. Morphomics may improve the transplant selection process and
      provide a greater assessment of prospective survival benefits.

PMID- 28758237
TI  - Towards an understanding of how appraisal of doctors produces its effects: a
      realist review.
AB  - CONTEXT: Revalidation was launched in the UK to provide assurances to the public
      that doctors are up to date and fit to practice. Appraisal is a fundamental
      component of revalidation. Approximately 150 000 doctors are appraised annually,
      costing an estimated L97 million over 10 years. There is little understanding of
      the theory of how and why appraisal is supposed to produce its effects. A realist
      review of the literature was utilised to explore these issues, as they generate
      context-mechanism-outcome (CMO) configurations, resulting in the creation of
      theories of how and why appraisal of doctors produces its effects. METHODS: A
      programme theory of appraisal was created by convening stakeholders in appraisal
      and searching a database of research on appraisal of doctors. Supplementary
      searches provided literature on theories identified in the programme theory.
      Relevant sections of texts relating to the programme theory were extracted from
      included articles, coded in NVivo and synthesised using realist logic of
      analysis. A classification tool categorised the included articles' contributions
      to programme theory. RESULTS: One hundred and twenty-five articles were included.
      Three mechanisms were identified: dissonance, denial and self-affirmation. The
      dissonance mechanism is most likely to cause outcomes of reflection and insight.
      Important contexts for the dissonance mechanism include the appraiser being
      highly skilled, the appraisee's working environment being supportive and the
      appraisee having the right attitude. The denial mechanism is more likely to be
      enacted if the opposite of these contexts occurs and could lead to game-playing
      behaviour. A skilled appraiser was also important in triggering the self
      affirmation mechanism, resulting in reflection and insight. The contexts,
      mechanisms and outcomes identified were, however, limited by a lack of evidence
      that could enable further refining of the CMO configurations. CONCLUSION: This
      review makes a significant contribution to our understanding of appraisal by
      identifying different ways that appraisal of doctors produces its effects.
      Further research will focus on testing the CMO configurations.

PMID- 28758238
TI  - Design, Synthesis, and Docking Study of Pyrimidine-Triazine Hybrids for GABA
      Estimation in Animal Epilepsy Models.
AB  - A series of new pyrimidine-triazine hybrids (4a-t) was designed and synthesized,
      from which potent anticonvulsant agents were identified. Most of the compounds
      exhibited promising anticonvulsant activity against the maximal electroshock
      (MES) and subcutaneous pentylenetetrazole (scPTZ) tests, along with minimal motor
      impairment with higher safety compared to the standard drugs, phenytoin and
      carbamazepine. In the series, 5-(4-(4-fluorophenyl)-6-(4-hydroxyphenyl)-2-thioxo
      5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4o) and 5-(6
      (4-hydroxy-3-methoxyphenyl)-4-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin
      1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4s) emerged as most potent
      anticonvulsant agents with median doses of 22.54 and 29.40 mg/kg (MES ED50 ),
      285.02 and 293.42 mg/kg (scPTZ ED50 ), and 389.11 and 412.16 mg/kg (TD50 ),
      respectively. Docking studies were also performed for all synthesized compounds
      to get insight into the binding pattern toward the GABAA receptor as a possible
      mechanism of their anticonvulsant action, and in silico ADME studies were carried
      out to predict the safety and stability of the molecules. The increased GABA
      level in the experimental animals in the neurochemical estimation assay confirmed
      their GABAergic modulating activity. The most potent compounds were also
      evaluated for their neurotoxic and hepatotoxic effects. Fortunately, they did not
      show any sign of neurotoxicity or hepatotoxicity, suggesting that they have a
      broad spectrum of anticonvulsant activity with a large safety margin. Together,
      this research suggested that 4o and 4s may serve as leads in the discovery and
      development of new anticonvulsant drugs.

PMID- 28758240
TI  - Effects of imaging gradients in sequences with varying longitudinal storage time
      Case of diffusion exchange imaging.
AB  - PURPOSE: To illustrate the potential bias caused by imaging gradients in
      correlation MRI sequences using longitudinal magnetization storage (LS) and
      examine the case of filter exchange imaging (FEXI) yielding maps of the apparent
      exchange rate (AXR). METHODS: The effects of imaging gradients in FEXI were
      observed on yeast cells. To analyze the AXR bias, signal evolution was calculated
      by applying matrix exponential operators. RESULTS: A sharp threshold for the
      slice thickness was identified, below which the AXR is increasingly
      underestimated. The bias can be understood in terms of an extended low-pass
      diffusion filtering during the LS interval, which is more pronounced at lower
      exchange rates. For a total exchange rate constant larger than 1 s-1 , the AXR
      bias is expected to be negligible when slices thicker than 2.5 mm are used.
      CONCLUSION: In correlation experiments like FEXI, relying on LS with variable
      duration, imaging gradients may cause disrupting effects that cannot be easily
      mitigated and should be carefully considered for unbiased results. In typical
      clinical applications of FEXI, the imaging gradients are expected to cause a
      negligible AXR bias. However, the AXR bias may be significant in preclinical
      settings or whenever thin imaging slices are used. Magn Reson Med 79:2228-2235,
      2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

PMID- 28758239
TI  - Diagnostic Utility of Wireless Video-Electroencephalography in Unsedated Dogs.
AB  - BACKGROUND: Poor agreement between observers on whether an unusual event is a
      seizure drives the need for a specific diagnostic tool provided by video
      electroencephalography (video-EEG) in human pediatric epileptology. OBJECTIVE:
      That successful classification of events would be positively associated with
      increasing EEG recording length and higher event frequency reported before video
      EEG evaluation; that a novel wireless video-EEG technique would clarify whether
      unusual behavioral events were seizures in unsedated dogs. ANIMALS: Eighty-one
      client-owned dogs of various breeds undergoing investigation of unusual
      behavioral events at 4 institutions. METHODS: Retrospective case series:
      evaluation of wireless video-EEG recordings in unsedated dogs performed at 4
      institutions. RESULTS: Electroencephalography achieved/excluded diagnosis of
      epilepsy in 58 dogs (72%); 25 dogs confirmed with epileptic seizures based on
      ictal/interictal epileptiform discharges, and 33 dogs with no EEG abnormalities
      associated with their target events. As reported frequency of the target events
      decreased (annually, monthly, weekly, daily, hourly, minutes, seconds), EEG was
      less likely to achieve diagnosis (P < 0.001). Every increase in event frequency
      increased the odds of achieving diagnosis by 2.315 (95% confidence interval: 1.36
      4.34). EEG recording length (mean = 3.69 hours, range: 0.17-22.5) was not
      associated (P = 0.2) with the likelihood of achieving a diagnosis. CONCLUSIONS
      AND CLINICAL IMPORTANCE: Wireless video-EEG in unsedated dogs had a high success
      for diagnosis of unusual behavioral events. This technique offered a reliable
      clinical tool to investigate the epileptic origin of behavioral events in dogs.

PMID- 28758241
TI  - In vivo phase imaging of human epiphyseal cartilage at 7 T.
AB  - PURPOSE: To assess the potential clinical utility of in vivo susceptibility
      weighted imaging and quantitative susceptibility mapping of growth cartilage in
      the juvenile human knee at 7 T. METHODS: High-resolution gradient-echo images of
      the knees of six healthy children and adolescents aged 6 to 15 were acquired with
      a 28-channel coil at 7 T. Phase images from the coils were combined using a short
      echo-time reference scan method (COMPOSER). RESULTS: Veins oriented perpendicular
      to the static B0 field appeared doubled in susceptibility-weighted imaging, but
      not quantitative susceptibility mapping. Veins and layers in the cartilage were
      visible in all children up to the age of 13. CONCLUSIONS: Phase imaging using
      susceptibility-weighted imaging and quantitative susceptibility mapping allows
      the in vivo visualization of veins and layers in human growth cartilage. Magn
      Reson Med 79:2149-2155, 2018. (c) 2017 International Society for Magnetic
      Resonance in Medicine.

PMID- 28758242
TI  - Should disclosure of conflicts of interest in medicine be made public? Medical
      students' views.
AB  - CONTEXT: Conflicts of interest (CoIs) are considered to be ubiquitous in health
      care and biomedicine. The disclosure of relevant interests is a first step in
      managing conflicts, although its usefulness is contested. Although several
      countries have mandated the public disclosure of doctors' financial relationships
      with the pharmaceutical industry, little is known about medical students'
      understanding of mandatory public disclosure. METHODS: Six 90-minute focus groups
      were conducted with medical students in New South Wales, Australia. Participants
      ranged from first- to final-year students. Students were asked about their
      understanding and experiences of CoIs and, more specifically, for their views on
      and experiences of disclosure in medical education, mandatory disclosure and
      public registers. Qualitative data analysis was based on a framework approach.
      RESULTS: Participants were generally not supportive of mandatory public
      disclosure of financial relationships with industry, principally because of
      concerns about privacy, control over disclosure, and others' (mis)interpretations
      of disclosures. Further, they did not know how to assess the disclosures
      presented to them as part of their medical education and described a wide range
      of reactions to disclosed information. CONCLUSIONS: This study suggests that
      students are currently not well prepared for mandatory public disclosure of CoIs.
      The subsequent discussion draws on Bourdieu's doxa to highlight assumptions of
      altruism in medicine, assumptions that are potentially in tension with recent
      events that have exposed doctors to moral scrutiny by the public. Medical
      students could be better prepared for future obligations by encouraging
      disclosures, and contextualising and helping students to interpret them.
      Disclosure as a box-ticking exercise is unlikely to achieve goals implied by
      transparency, but a more reflective approach may assist both scrutinisers and the
      scrutinised.

PMID- 28758243
TI  - Enteroscopy-overtube-assisted over-the-wire stent placement to treat an enteral
      stenosis.

PMID- 28758244
TI  - Lung transplantation delays gastric motility in patients without prior
      gastrointestinal surgery-A single-center experience of 412 consecutive patients.
AB  - PURPOSE: To examine the impact of lung transplantation on gastric motility.
      METHODS: Adult recipients at a large, single center, who were retrospectively
      evaluated with solid gastric emptying (SGE) study post-lung transplantation, but
      had no history of gastrointestinal intervention (ie, pyloroplasty or
      fundoplication), were selected between June 2005 and August 2013. Multivariable
      logistic regression was performed to determine risk factors associated with
      delayed gastric emptying (DGE) after transplantation. RESULTS: Delayed gastric
      emptying (DGE) was noted in 236 patients (57%) after transplantation. On
      multivariable logistic regression, an underlining diagnosis of cystic fibrosis
      (CF)/bronchiectasis (adjusted odds ratio [AOR] 3.26, P < .01) was a significant
      risk factor in predicting DGE after lung transplantation. There was no survival
      difference between patients with postoperative DGE vs those without (log-rank
      test P = .53). CONCLUSIONS: Delayed gastric emptying is very common following
      lung transplantation, occurring in over half of all lung transplant recipients
      with increased prevalence in patients with CF. The association with cystic
      fibrosis could be secondary to extra-pulmonary manifestations of the underlying
      disease or indicative of increased intraoperative vagal nerve injury. We
      speculate that DGE may play a substantial role in the increased reflux-induced
      allograft injury seen after lung transplantation. Further prospective studies are
      needed to validate this hypothesis.

PMID- 28758246
TI  - Endoscopic hemostasis for spurting duodenal bleeding using dual red imaging.

PMID- 28758245
TI  - The toxicity of paracetamol-codeine combination in overdose is an unresolved
      issue.

PMID- 28758247
TI  - Pulsed-Dye Laser Treatment of Port-Wine Stains in Children: Useful Tips to Avoid
      General Anesthesia.
AB  - Pulsed dye laser (PDL) treatment of port-wine stains (PWSs) in children is a
      common procedure performed in most laser units. Pain assessment in our younger
      patients is a major concern, especially in those with extensive PWSs. The use of
      general anesthesia (GA) results in pain-free treatment, but its effects on the
      developing brain are far from totally understood. Thus we propose some tips that
      avoid the use of GA in most of our young patients, including the use of topical
      anesthetics and cooling systems, large laser spot size and high frequencies,
      early and frequent treatment with parents present, and the "introduction" and
      "pressure" techniques, among others.

PMID- 28758248
TI  - Ratio-adjustable power splitters for array-compressed parallel transmission.
AB  - PURPOSE: To implement and validate low-loss ratio-adjustable power splitters
      (RAPS) for array-compressed parallel transmission (acpTx). METHODS: In acpTx, a
      small number of transmit channels drive a larger number of transmit coils, which
      are connected via an array compression network that implements optimized coil-to
      channel combinations. Previous networks comprised a bank of power splitters,
      followed by attenuators to implement the amplitudes of the compression weights
      for each coil, but this resulted in high power dissipation in the network.
      Recognizing that an acpTx network need only implement relative attenuations
      between outputs, a RAPS circuit was developed which combines power splitting and
      relative attenuation, and has low insertion loss. RAPS circuits were
      experimentally validated and used to build an array compression network for a one
      channel-to-four-coil spiral acpTx excitation experiment. RESULTS: Bench tests
      showed that the RAPS circuits came within 0.05 dB of the desired output ratios,
      and power dissipation was approximately 0.5 dB (10%). The spiral excitation
      experiment showed that the ability to optimally drive four coils with a single
      channel reduced excitation error by 46% compared to driving one coil, without
      using attenuators in the array compression network. CONCLUSION: RAPS circuits
      enable the construction of low-loss array compression networks for parallel
      transmission. Magn Reson Med 79:2422-2431, 2018. (c) 2017 International Society
      for Magnetic Resonance in Medicine.

PMID- 28758249
TI  - Vulvar lymphangioma circumscriptum: comparison of primary and acquired forms in a
      cohort of 57 patients.

PMID- 28758250
TI  - Thermal injury caused by the explosion of a lithium-ion mobile phone battery.

PMID- 28758252
TI  - Lunch-time food source is associated with school hour and school day diet quality
      among Canadian children.
AB  - BACKGROUND: There is limited research on the dietary behaviours of Canadian
      children at school, including where students obtain food from during school hours
      or whether lunch-time food source influences diet quality. METHODS: Nationally
      representative cross-sectional data from 24-h dietary recalls were analysed from
      the 2004 Canadian Community Health Survey (n = 4589). Dietary outcomes included
      school hour and school day dietary intakes and School Healthy Eating Index (S
      HEI) scores. Survey-weighted covariate-adjusted linear regression models examined
      differences in dietary outcomes across lunch-time food source groups. RESULTS:
      The majority of children (72.8%) reported bringing lunch from home, whereas fewer
      students obtained lunch from off-campus locations (11.6%), schools (9.6%) or
      skipped lunch (5.9%). Compared to off-campus lunches, home-packed lunches were
      significantly higher in fibre, vitamins A, D and C, thiamin, magnesium, iron,
      grains, vegetables and fruit, but lower in total calories, fat and calories from
      minimally nutritious foods. Average school hour diet quality required improvement
      for all age groups, although S-HEI scores did not differ significantly by lunch
      time food source among 6-8-year-old children. However, for children age 9-17
      years, bringing a home-packed lunch was associated with significantly higher S
      HEI scores compared to students obtaining lunch from off-campus locations. After
      adjusting for age and sex, lunch-time food source was also significantly
      associated with whole day dietary quality. CONCLUSIONS: Although the nutritional
      quality of off-campus lunches was lower than home-packed lunches, the quality of
      foods was suboptimal, regardless of food source. Strategies are needed to enhance
      access to nutritious foods on campus and improve the nutritional quality of
      packed lunches, which supply the majority of lunch-time foods consumed by
      Canadian children.

PMID- 28758251
TI  - Insulin action in the brain: Roles in energy and glucose homeostasis.
AB  - A growing body of evidence from research in rodents and humans has identified
      insulin as an important neuoregulatory peptide in the brain, where it coordinates
      diverse aspects of energy balance and peripheral glucose homeostasis. This review
      discusses where and how insulin interacts within the brain and evaluates the
      physiological and pathophysiological consequences of central insulin signalling
      in metabolism, obesity and type 2 diabetes.

PMID- 28758253
TI  - miR-182 selectively targets HOXA10 in goat endometrial epithelium cells in vitro.
AB  - Proper HOXA10 expression was essential for endometrial receptivity what was
      crucial for successful embryo implantation in mammalian. This study confirmed
      that miR-182 regulated the expression levels of HOXA10 by binding to its 3' UTR,
      selectively downregulated HOXA10 in goat endometrial epithelium cells (gEECs) but
      not stromal cell (gESCs) in vitro. However, HOXA10 and miR-182 both up-expressed
      in the goat endometrium at gestational day 15 (D15) compared with gestational day
      5 (D5), suggesting that there were some other factors regulated the expression of
      HOXA10 during the development of goat endometrium in vivo. What's more, HOXA10
      gene silencing (HOXA10-siRNA) resulted in gEECs apoptosis in vitro, and it
      regulated the protein levels of oestrogen receptor a (ERa), progesterone receptor
      B (PRb), insulin-like growth factor 1 receptor (IGF1R), BCL-2, pleiotrophin
      (PTN), AKT and p-JNK in gEECs. Furthermore, HOXA10 might regulate the protein
      levels of endometrial receptivity biomarker genes, including vascular endothelial
      growth factor (VEGF), osteopontin (OPN), cyclooxygenase-2 (COX-2) and prolactin
      receptor (PRLR) in gEECs. In conclusion, miR-182 targeted HOXA10 selectively in
      EECs in vitro, and HOXA10 played an important role in maintaining the function of
      EECs in dairy goats.

PMID- 28758254
TI  - Exceptional High-Performance of Pt-Based Bimetallic Catalysts for Exclusive
      Detection of Exhaled Biomarkers.
AB  - Achieving an improved understanding of catalyst properties, with ability to
      predict new catalytic materials, is key to overcoming the inherent limitations of
      metal oxide based gas sensors associated with rather low sensitivity and
      selectivity, particularly under highly humid conditions. This study introduces
      newly designed bimetallic nanoparticles (NPs) employing bimetallic Pt-based NPs
      (PtM, where M = Pd, Rh, and Ni) via a protein encapsulating route supported on
      mesoporous WO3 nanofibers. These structures demonstrate unprecedented sensing
      performance for detecting target biomarkers (even at p.p.b. levels) in highly
      humid exhaled breath. Sensor arrays are further employed to enable pattern
      recognition capable of discriminating between simulated biomarkers and controlled
      breath. The results provide a new class of multicomponent catalytic materials,
      demonstrating potential for achieving reliable breath analysis sensing.

PMID- 28758255
TI  - Leucemia inhibitory factor; investigating the time-dependent effect on viability
      of vitrified bovine embryos.
AB  - Leucemia inhibitory factor (LIF) is involved in various reproductive processes,
      including sperm development, regulation of ovulation, as well as blastocyst
      formation, hatching and implantation in embryos. Moreover, LIF has also been
      shown significantly to enhance the blastocyst formation rates of bovine embryos,
      a finding that remains controversial. Our purpose was to investigate time
      dependent effect of LIF on bovine embryo culture, especially in terms of addition
      timing. Presumptive zygotes were cultured in five different groups. In this
      study, 100 ng/ml LIF was added to the culture medium were as follows; control:
      SOF alone, group A: at day 0 (fertilization day), group B: at day 4 post
      insemination (p.i.), group C: at day 4 to 7 (p.i. before vitrification) and group
      D: at day 8 (p.i. after thawing). Addition of LIF to the culture medium at day 4
      significantly increased the percentage of blastocyst rate when compared day 0,
      day 4 at 6/7 and control group (41.8% versus 24.3%, 19.7%, 34.6%). In conclusion,
      the addition of LIF only on day 4 (p.i.) to the culture medium was found to be
      beneficial for bovine embryonic development based on several measures, including
      blastocysts rate, re-expansion rate and cellular cryotolerance after
      vitrification.

PMID- 28758256
TI  - Hospitalization and outcomes attributed to epidermal necrolysis in the United
      States: predictors of mortality.

PMID- 28758257
TI  - Atopic dermatitis is associated with autoimmune but not with cardiovascular
      comorbidities in a random sample of the general population in Leipzig, Germany.

PMID- 28758258
TI  - Dominant follicles development and estradiol-17beta concentrations in non
      ovulating and ovulating post-partum Bulgarian Murrah buffaloes.
AB  - This study was designed to evaluate the dominant follicles development and the
      estradiol-17beta concentrations in non-ovulating and ovulating post-partum
      buffaloes. Sixteen Bulgarian Murrah buffaloes were submitted to transrectal
      ultrasonographic examination from the 1st post-partum day until day 50, 3 days
      apart. The follicular diameter of the different categories of follicles and the
      ovulations was recorded. The animals were allocated into two groups: I (n = 6)
      non-ovulating and II (n = 10) ovulating buffaloes. Serum estradiol-17beta
      concentrations on the days for dominant follicle registration were measured by
      enzyme-linked immunosorbent assay. The results were statistically processed by
      analysis of variance, non-parametric and correlation analysis. The mean intervals
      between calving and first dominant follicle detection differed significantly (p <
      .05) among the groups (19.5 +/- 6.2 vs. 13.8 +/- 5.1 days), while the mean
      intervals between registered dominant follicles from two successive waves were
      comparable. The mean follicular diameters for the same category follicles in both
      groups were similar. Different estradiol-17beta concentrations (p < .05) for the
      first dominant follicle between non-ovulating (23.5 +/- 7.0 pg/ml) and ovulating
      (33.3 +/- 8.4 pg/ml) buffaloes were determined. The cumulative percentages of
      buffaloes with firstly detected dominant follicle and ovulating animals
      correlated positively (r >= .84; p < .05) to post-partum days. In conclusion, non
      ovulating and ovulating post-partum Bulgarian Murrah buffaloes showed differences
      in the development of the first dominant follicle and estradiol-17beta
      concentrations during the time of dominant follicles detection.

PMID- 28758259
TI  - Transient receptor potential melastatin 4 channel is required for rat dental pulp
      stem cell proliferation and survival.
AB  - OBJECTIVES: Investigate the role of the transient receptor potential melastatin 4
      (TRPM4) channel in rat dental pulp stem cell (DPSC) proliferation and survival.
      MATERIALS AND METHODS: Immunofluorescence and FACS analysis were used to detect
      the stem cell marker CD90. Alizarin Red S and Oil Red O staining were used to
      identify osteoblast and adipocyte differentiation, respectively. To characterize
      TRPM4, patch-clamp recordings were obtained from single cells in the whole-cell
      configuration mode. The significance of TRPM4 for proliferation and survival was
      examined with 9-phenanthrol, a TRPM4 inhibitor during a 96-hour period of
      culture. Real-time Ca2+ imaging analysis with Fura-2AM was used to investigate
      the impact of TRPM4 on intracellular Ca2+ signals. RESULTS: DPSCs were CD90
      positive and differentiated into osteoblasts. Patch-clamp recordings revealed
      currents typical of TRPM4 that were Ca2+ -activated, voltage-dependent and Na+ 
      conducting. Inhibition of TRPM4 resulted in a significant reduction in the cell
      population after a 96-hr period of culture and transformed the biphasic pattern
      of intracellular Ca2+ signalling into sustained oscillations. CONCLUSIONS: Rat
      DPSCs have stem cell characteristics and functional TRPM4 channels that are
      required for proliferation and survival. These data suggest that the shape and
      frequency of intracellular Ca2+ signals may mediate stem cell proliferation and
      survival.

PMID- 28758260
TI  - Vapomechanically Responsive Motion of Microchannel-Programmed Actuators.
AB  - Materials that respond rapidly and reversibly to external stimuli currently stand
      among the top choices as actuators for real-world applications. Here, a series of
      programmable actuators fabricated as single- or bilayer elements is described
      that can reversibly respond to minute concentrations of acetone vapors. By using
      templates, microchannel structures are replicated onto the surface of two highly
      elastic polymers, polyvinylidene fluoride (PVDF) and polyvinyl alcohol, to induce
      chiral coiling upon exposure to acetone vapors. The vapomechanical coiling is
      reversible and can be conducted repeatedly over 100 times without apparent
      fatigue. If they are immersed in liquid acetone, the actuators are saturated with
      the solvent and temporarily lose their motility but regain their shape and
      activity within seconds after the solvent evaporates. The desorption of acetone
      from the PVDF layer is four times faster than its adsorption, and the actuator
      composed of a single PVDF layer maintains its ability to move over an acetone
      soaked filter paper even after several days. The controllable and reproducible
      sensing capability of this smart material can be utilized for actuating dynamic
      elements in soft robotics.

PMID- 28758261
TI  - Comparison of two picosecond lasers to a nanosecond laser for treating tattoos: a
      prospective randomized study on 49 patients.
AB  - BACKGROUND: Q-switched nanosecond lasers demonstrated their efficacy in treating
      most types of tattoos, but complete disappearance is not always achieved even
      after performing numerous laser sessions. Picosecond lasers are supposed to be
      more efficient in clearing tattoos than nanosecond lasers, but prospective
      comparative data remain limited. OBJECTIVE: To compare on different types of
      tattoos the efficacy of a nanosecond laser with two types of picosecond lasers.
      METHODS: We conducted a prospective randomized study performed from December 2014
      to June 2016 on adult patients with all types of tattoos. The tattoos were
      divided into two halves of equal size. After randomization, half of the tattoo
      was treated with a picosecond laser and the other half with a nanosecond laser.
      The evaluation was performed on standardized pictures performed before treatment
      and 2 months after the last session, by two physicians, not involved in the
      treatment, blinded on the type of treatments received. The main end point was a
      clearance above 75% of the tattoos. RESULTS: A total of 49 patients were
      included. Professional tattoos represented 85.7%, permanent make-up 8.2% and non
      professional tattoo 6.1%. The majority were black or blue and 10.2% were
      polychromatic. No patient was lost during follow-up. A reduction of 75% or more
      of the colour intensity was obtained for 33% of the tattoos treated with the
      picosecond lasers compared to 14% with the nanosecond laser (P = 0.008). An
      improvement superior to 75% was obtained in 34% monochromic black or blue tattoos
      with the picosecond lasers compared to 9% for the nanosecond laser. Only one of
      the five polychromic tattoos achieved more than 75% of improvement with the two
      types of laser. CONCLUSION: Our results show a statistically significant
      superiority of the picosecond lasers compared to the nanosecond laser for tattoo
      clearance. However, they do not show better efficacy for polychromic tattoos and
      the difference in terms of side-effects was also minimal with a tendency of
      picosecond lasers to be less painful.

PMID- 28758262
TI  - Paraneoplastic pemphigus seen in four patients with haematological malignancies
      formerly treated with rituximab.

PMID- 28758263
TI  - Anti-epileptic drugs induce cutaneous lymphocyte-associated antigen
      downregulation leading to potential human herpes virus-7 reactivation in
      clinically asymptomatic patients.

PMID- 28758264
TI  - Supercapacitive Iontronic Nanofabric Sensing.
AB  - The study of wearable devices has become a popular research topic recently, where
      high-sensitivity, noise proof sensing mechanisms with long-term wearability play
      critical roles in a real-world implementation, while the existing mechanical
      sensing technologies (i.e., resistive, capacitive, or piezoelectric) have yet
      offered a satisfactory solution to address them all. Here, we successfully
      introduced a flexible supercapacitive sensing modality to all-fabric materials
      for wearable pressure and force sensing using an elastic ionic-electronic
      interface. Notably, an electrospun ionic fabric utilizing nanofibrous structures
      offers an extraordinarily high pressure-to-capacitance sensitivity (114 nF kPa-1
      ), which is at least 1000 times higher than any existing capacitive sensors and
      one order of magnitude higher than the previously reported ionic devices, with a
      pressure resolution of 2.4 Pa, achieving high levels of noise immunity and signal
      stability for wearable applications. In addition, its fabrication process is
      fully compatible with existing industrial manufacturing and can lead to cost
      effective production for its utility in emerging wearable uses in a foreseeable
      future.

PMID- 28758265
TI  - Risk of aortic aneurysm in patients with psoriasis: a retrospective cohort study.

PMID- 28758267
TI  - A Sensitive Luminescent Acetylacetone Probe Based on Zn-MOF with Six-Fold
      Interpenetration.
AB  - A novel metal-organic framework {[Zn(XL)2 ](ClO4 )2 ?6 H2 O}n (XL=N,N'
      bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxdiimide bi(1,2,4-triazole)) was
      synthesized and structurally characterized, presenting the first example of six
      fold interpenetrating 3 D framework with the topology type of sqc6, which
      displays high thermostability and solvent stability. Additionally, the
      luminescence investigations reveal that this MOF can sensitively and selectively
      detect acetylacetone with a detection limit of 1.72 ppm. More importantly, it is
      rather rare for an MOF-based luminescence probe to serve as a sensor to
      effectively detect acetylacetone.

PMID- 28758268
TI  - Noodle pattern: a new dermoscopic pattern for crusted scabies (Norwegian
      scabies).

PMID- 28758266
TI  - A pH-sensitive Macromolecular Prodrug as TLR7/8 Targeting Immune Response
      Modifier.
AB  - The chemical synthesis and biological activity of novel functionalized
      imidazoquinoline derivatives (ImQ) to generate Toll-like receptor (TLR) 7/8
      specific prodrugs are presented. In vivo activity of ImQs to induce inflammation
      was confirmed in zebrafish larvae. After covalent ligation to fully biodegradable
      polyphosphazenes (ImQ-polymer), the macromolecular prodrugs were designed to
      undergo intracellular pH-sensitive release of ImQs to induce inflammation through
      binding to endosomal TLR7/8 (danger signal). We showed ImQ dissociation from
      prodrugs at a pH 5 pointing towards endosomal prodrug degradability. ImQ-polymers
      strongly activated ovalbumin-specific T cells in murine splenocytes as shown by
      increased proliferation and expression of the IL-2 receptor (CD25) on CD8+ T
      cells accompanied by strong IFN-gamma release. ImQ prodrugs presented here are
      suggested to form the basis of novel nanovaccines, for example, for intravenous
      or intratumoral cancer immunotherapeutic applications to trigger physiological
      antitumor immune responses.

PMID- 28758269
TI  - Three-State Ferroelastic Switching and Large Electromechanical Responses in
      PbTiO3 Thin Films.
AB  - Leveraging competition between energetically degenerate states to achieve large
      field-driven responses is a hallmark of functional materials, but routes to such
      competition are limited. Here, a new route to such effects involving domain
      structure competition is demonstrated, which arises from strain-induced
      spontaneous partitioning of PbTiO3 thin films into nearly energetically
      degenerate, hierarchical domain architectures of coexisting c/a and a1 /a2 domain
      structures. Using band-excitation piezoresponse force microscopy, this study
      manipulates and acoustically detects a facile interconversion of different
      ferroelastic variants via a two-step, three-state ferroelastic switching process
      (out-of-plane polarized c+ -> in-plane polarized a -> out-of-plane polarized c-
      state), which is concomitant with large nonvolatile electromechanical strains
      (~1.25%) and tunability of the local piezoresponse and elastic modulus (>23%). It
      is further demonstrated that deterministic, nonvolatile writing/erasure of large
      area patterns of this electromechanical response is possible, thus showing a new
      pathway to improved function and properties.

PMID- 28758270
TI  - Prescription drug use during pregnancy in France: a study from the national
      health insurance permanent sample.
AB  - PURPOSE: To provide an up-to-date account of drug prescription during pregnancy
      in France from 2011 to 2014 using the permanent sample of the French national
      computerized healthcare database and with a focus on recommended
      supplementations, fetotoxic drugs and teratogenic drugs. METHODS: All pregnancies
      identified by the International Classification of Diseases, 10th Revision codes
      list in the hospitalization database, lasting more than 9 weeks of amenorrhea and
      whose delivery occurred between 01/01/2011 and 12/31/2014, were included. Drugs
      delivered between the trimester before and until the end of the pregnancy were
      included. Drug exposure prevalence was calculated for each year and according to
      pregnancy trimesters. RESULTS: The study included 28,491 pregnancies with a
      median number of 9 [5-13] (median [IQ range]) drugs delivered. The most
      prescribed drug class was antianemia (in 72.5% of exposed). The prescription rate
      of recommended vitamins (B9 and D) increased over the study period (+10%).
      Influenza vaccination also increased but remained at a low rate (1%). Exposure to
      fetotoxic drugs decreased as pregnancy advanced. Exposure to the main teratogenic
      antiepileptics was stable over the study period. Low-income pregnant women had a
      higher average drug consumption except for recommended vitamins. CONCLUSION:
      Pregnant French women are among the largest consumers of prescription medications
      worldwide. Overall, the dispensation trends observed in this study are in line
      with the recommendations of the French National College of Gynecologists and
      Obstetricians. Nevertheless, while being low, exposure to fetotoxic drugs,
      teratogenic drugs or those under safety alerts still occurred. Supplementations
      and vaccines in low-income pregnant women should also be increased.

PMID- 28758271
TI  - Visually stressful striped patterns alter human visual cortical functional
      connectivity.
AB  - Visually stressful striped patterns with a spatial frequency (SF) of around 3
      cycles per degree (cpd) can induce perceptual illusions/distortions and visual
      discomfort in most people, headaches in patients with migraine, and seizures in
      patients with photosensitive epilepsy. Patterns with SF ~0.3 cpd have no such
      effects and are not uncomfortable to look at (non-stressful). The effects of the
      striped patterns on visual cortical activation have been investigated, but their
      effects on the visual cortical network remain to be studied. A prolonged visual
      stimulation with stressful patterns may alter the functional connections within
      the visual system, and their relationship with other networks. Using resting
      state fMRI, this study revealed that the functional connections within the visual
      system were significantly enhanced by visually stressful stimulation. The
      functional connectivity between V1 and other brain regions was also significantly
      modified. Non-stressful stimulation produced no such significant effects. More
      importantly, the effects outlasted the stimulation, and this applied both to
      those effects within and those beyond the visual cortex, suggesting that repeated
      prolonged visual stimulation with stressful patterns may alter functional
      connections of the brain and this might be utilized as a visual neuromodulation
      approach for treatments of visually triggered headaches in migraine patients and
      visually induced seizures in patients with photosensitive epilepsy. Hum Brain
      Mapp 38:5474-5484, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28758272
TI  - Transoral robotic retropharyngeal node dissection in oropharyngeal squamous cell
      carcinoma: Patterns of metastasis and functional outcomes.
AB  - BACKGROUND: Assessment of the retropharyngeal lymph nodes is essential in the
      treatment for oropharyngeal squamous cell carcinoma (SCC). Transoral robotic
      retropharyngeal lymph node dissection (RPLND) may provide valuable staging
      information and guide selection of adjuvant therapy in a transoral robotic
      surgery (TORS) treatment paradigm. METHODS: Outcomes were compared between 30
      patients with oropharyngeal SCC with tonsillar primaries undergoing RPLND and 37
      stage-matched cases without RPLND. RESULTS: Retropharyngeal metastasis was
      confirmed in 6 patients undergoing RPLND. Compared with 37 stage-matched
      controls, there were no differences in length of stay, length of feeding tube
      dependence, net change in perioperative weight, or rates of hemorrhage and
      postoperative complications. RPLND altered adjuvant treatment recommendations in
      1 of 30 patients. CONCLUSION: RPLND is technically feasible by a purely transoral
      robotic approach. Its performance is not associated with worse swallowing
      outcomes or rates of complication. In select patients, RPLND may provide valuable
      staging information and guide the selection of adjuvant therapy.

PMID- 28758273
TI  - Assessment of computed tomography derived cricoid cartilage and tracheal
      dimensions to evaluate degree of cricoid narrowing in brachycephalic dogs.
AB  - The aims of this observational, analytical, retrospective study were to (i)
      obtain computed tomographic (CT) cricoid dimensions (height, width, and
      transverse-sectional area), (ii) compare the cricoid dimensions between
      brachycephalic and mesaticephalic breeds, and (iii) compare cricoid cartilage
      dimensions between dogs without and affected with brachycephalic airway syndrome.
      The study is important to help to further evaluate and understand the anatomical
      components of brachycephalic airway syndrome. Measurements were performed in 147
      brachycephalic and 59 mesaticephalic dogs. The cricoid cartilage was found to be
      significantly more oval in Pugs and French Bulldogs compared to mesaticephalic
      breeds. The cricoid cartilage transverse-sectional area was smallest for the Pug
      and, after adjusting for weight, significantly smaller for Pugs (P < 0.001),
      Boston Terriers (P = 0.001), and French Bulldogs (P < 0.001) compared to Jack
      Russell Terriers. The tracheal transverse-sectional area at C4 of English
      Bulldogs was significantly smaller than for Jack Russell Terriers (P = 0.005) and
      Labradors (P < 0.001). The cricoid cartilage transverse-sectional area:weight
      ratio was significantly lower in brachycephalic breeds compared to mesaticephalic
      breeds (P < 0.001). The cricoid cartilage:trachea at C4 transverse-sectional area
      for brachycephalic dogs was significantly larger than for mesaticephalic dogs
      (<0.001), demonstrating that the trachea was the narrowest part of the airway. No
      significant differences were found for cricoid dimensions between dogs affected
      with and without brachycephalic airway syndrome. However, large individual
      variation was found among the brachycephalic breeds and further studies
      investigating the relationship between cricoid cartilage size, laryngeal
      collapse, concurrent tracheal hypoplasia, and/or severity of brachycephalic
      airway syndrome are warranted.

PMID- 28758274
TI  - Pregnancy and infant outcomes including major congenital malformations among
      women with chronic inflammatory arthritis or psoriasis, with and without
      etanercept use.
AB  - PURPOSE: Objectives were to quantify prevalence estimates of pregnancy and infant
      outcomes including major congenital malformations (MCMs) by etanercept (ETN)
      exposure among infants born to women with chronic inflammatory arthritis (cIA) or
      psoriasis (PsO). METHODS: Claims-based data delineated pregnancy exposures and
      outcomes of live or nonlive births among women with cIA and PsO (ETN exposed,
      unexposed) and general population (GP) comparators. Infant outcomes were
      determined for live-born infants covered by the mother's insurer. Medical records
      were obtained from all accessible mother-infant pairs with claims for MCMs and a
      random sample of mothers. Multivariable logistic regression estimated the odds
      ratios (ORs) of having at least one algorithm-defined MCM in the ETN-exposed
      cohorts versus unexposed comparators. RESULTS: Prevalence estimates for pregnancy
      outcomes were comparable across cIA and PsO cohorts. Algorithm-defined prevalence
      estimates of having at least one MCM were 6.1% (ETN exposed), 5.5% (unexposed),
      and 5.7% (GP cohort) for the cIA cohort; PsO cohort estimates were 2.0%, 4.2%,
      and 4.7%, respectively. The ETN-exposure ORs for having at least one algorithm
      defined MCM among infants of cIA mothers was 1.03 (95%CI: 0.51-2.10) and 0.39
      (95%CI: 0.05-2.98) among infants of PsO mothers. Logistic regression with inverse
      probability of treatment weighting that included disease state resulted in an OR
      of 0.65 (0.24, 1.72). CONCLUSIONS: Overall, this study did not identify any new
      safety concerns associated with the use of etanercept during pregnancy.
      Etanercept, along with the other TNFis, remains a treatment without well
      controlled clinical trials in pregnant women. Patients should continue to consult
      their doctor regarding benefit risk decisions of TNFi therapy during pregnancy.

PMID- 28758275
TI  - Developing a typology of mobile phone usage in social care: A critical review of
      the literature.
AB  - The ways in which mobile phones have transformed the boundaries of time and space
      and the possibilities of communication have profoundly affected our lives.
      However, there is little research on the use of mobiles in social care though
      evidence is emerging that mobile phones can play an important role in delivering
      services. This paper is based on a scoping review of the international literature
      in this area. A typology of mobile interventions is suggested. While most mobile
      phone interventions remain unidirectional and sit within traditional social care
      service provider-service user relationships, a minority are bi- or
      multidirectional and contain within them the potential to transform these
      traditional relationships by facilitating a collective development of social
      networks and social capital. Such transformations are accompanied by a range of
      issues and dilemmas that have made many service providers reluctant to engage
      with new technologies. We suggest that our typology is a useful model to draw on
      when researching the use of mobile phones in social care to support and empower
      isolated, marginalised and vulnerable service users.

PMID- 28758276
TI  - Brief Report: Human Acute Myeloid Leukemia Reprogramming to Pluripotency Is a
      Rare Event and Selects for Patient Hematopoietic Cells Devoid of Leukemic
      Mutations.
AB  - Induced pluripotent stem cell reprogramming has provided critical insights into
      disease processes by modeling the genetics and related clinical pathophysiology.
      Human cancer represents highly diverse genetics, as well as inter- and intra
      patient heterogeneity, where cellular model systems capable of capturing this
      disease complexity would be invaluable. Acute myeloid leukemia (AML) represents
      one of most heterogeneous cancers and has been divided into genetic subtypes
      correlated with unique risk stratification over the decades. Here, we report our
      efforts to induce pluripotency from the heterogeneous population of human
      patients that represents this disease in the clinic. Using robust optimized
      reprogramming methods, we demonstrate that reprogramming of AML cells harboring
      leukemic genomic aberrations is a rare event with the exception of those with de
      novo mixed-lineage leukemia (MLL) mutations that can be reprogrammed and model
      drug responses in vitro. Our findings indicate that unlike hematopoietic cells
      devoid of genomic aberrations, AML cells harboring driver mutations are
      refractory to reprogramming. Expression of MLL fusion proteins in AML cells did
      not contribute to induced reprogramming success, which continued to select for
      patient derived cells devoid of AML patient-specific aberrations. Our study
      reveals that unanticipated blockades to achieving pluripotency reside within the
      majority of transformed AML patient cells. Stem Cells 2017;35:2095-2102.

PMID- 28758277
TI  - Fusion of the genes BRD8 and PHF1 in endometrial stromal sarcoma.
AB  - We present a new endometrial stromal sarcoma (ESS)-associated genomic
      rearrangement involving chromosome arms 5p and 6p and leading to the formation of
      a BRD8-PHF1 fusion gene. The PHF1 (PHD finger protein 1) gene, from 6p21, is
      known to be rearranged in ESS in a promiscuous way inasmuch as it has been shown
      to recombine with JAZF1, EPC1, MEAF6, and now also with BRD8, in tumors of this
      type. In all rearrangements of PHF1, including the present one, a recurrent theme
      is that the entire coding part of PHF1 constitutes the 3' end of the fusion. BRD8
      (bromodomain containing 8) encodes a protein which is involved in regulation of
      protein acetylation and/or histone acetyl transferase activity. All the genetic
      fusions identified so far in ESS appear to recombine genes involved in
      transcriptional regulation, that is, polycomb group complex-mediated and aberrant
      methylation/acetylation genes. This adds to the likelihood that the new BRD8-PHF1
      shares the same pathogenetic mechanism as the other ESS-specific rearrangements.

PMID- 28758278
TI  - Clinical and imaging findings, treatments, and outcomes in 27 dogs with imaging
      diagnosed trigeminal nerve sheath tumors: A multi-center study.
AB  - The clinical behavior of canine trigeminal nerve sheath tumors and benefits of
      previously reported treatments are incompletely defined. Aims of this
      retrospective, multicenter, observational study were to describe clinical signs,
      tumor localization characteristics, treatments, and clinical outcomes in a group
      of dogs with this neoplasm. Databases at four hospitals were reviewed for dogs
      with a trigeminal nerve sheath tumor diagnosis, magnetic resonance imaging (MRI)
      studies, and presentation between 2004 and 2014. A single observer recorded
      medical record findings and two observers recorded MRI characteristics by
      consensus. A total of 27 dogs met inclusion criteria (15 treated with
      stereotactic radiation therapy and 12 unirradiated). Two unirradiated dogs were
      excluded from outcome analyses. The most common presenting signs were masticatory
      muscle atrophy (26 dogs), neurologic signs referable to intracranial disease
      (13), and ocular disease (12). Based on MRI findings, all dogs had disease
      extending centrally at the level of the brainstem. The most commonly affected
      trigeminal nerve branches were the mandibular (26 dogs), maxillary (22), and
      ophthalmic (10). Of 15 dogs treated with stereotactic radiation therapy, one had
      improved muscle atrophy, and six had poor ocular health after treatment.
      Neurologic signs improved in 4/5 dogs with intracranial signs. Overall median
      survival time for the 10 unirradiated dogs with available follow-up was 12 days
      and 441 days for the 15 stereotactic radiation therapy dogs. Mean survival times
      between these groups were not significantly different (mean 95% CI for
      unirradiated dogs was 44-424 days and mean 95% CI for stereotactic radiation
      therapy dogs was 260-518 days).

PMID- 28758279
TI  - Life stage dependent responses to desiccation risk in the annual killifish
      Nothobranchius wattersi.
AB  - To assess whether the annual killifish Nothobranchius wattersi responds
      plastically to a desiccation risk and whether this response is life stage
      dependent, life-history traits such as maturation time, fecundity and life span
      were experimentally measured in N. wattersi that were subjected to a drop in
      water level either as juveniles, as adults or both as juveniles and adults. Fish
      that were exposed to simulated pool drying as juveniles did not show changes in
      reproductive output or life span. Adults reacted by doubling short term egg
      deposition at the cost of a shorter lifespan. Overall, these results suggest that
      annual fish species can use phenotypic plasticity to maximize their reproductive
      output when faced with early pond drying, but this response appears to be life
      stage specific. In addition to frogs and aquatic insects, phenotypic plasticity
      induced by forthcoming drought is now also confirmed in annual fishes and could
      well be a common feature of the limited number of fish taxa that manage to
      survive in this extreme environment.

PMID- 28758280
TI  - Interpretation of functional renal MRI findings: Where physiology and imaging
      sciences need to talk across domains.

PMID- 28758281
TI  - Response to "Interpretation of functional renal MRI findings: Where physiology
      and imaging sciences need to talk across domains".

PMID- 28758282
TI  - Phylogenetic estimates of diversification rate are affected by molecular rate
      variation.
AB  - Molecular phylogenies are increasingly being used to investigate the patterns and
      mechanisms of macroevolution. In particular, node heights in a phylogeny can be
      used to detect changes in rates of diversification over time. Such analyses rest
      on the assumption that node heights in a phylogeny represent the timing of
      diversification events, which in turn rests on the assumption that evolutionary
      time can be accurately predicted from DNA sequence divergence. But there are many
      influences on the rate of molecular evolution, which might also influence node
      heights in molecular phylogenies, and thus affect estimates of diversification
      rate. In particular, a growing number of studies have revealed an association
      between the net diversification rate estimated from phylogenies and the rate of
      molecular evolution. Such an association might, by influencing the relative
      position of node heights, systematically bias estimates of diversification time.
      We simulated the evolution of DNA sequences under several scenarios where rates
      of diversification and molecular evolution vary through time, including models
      where diversification and molecular evolutionary rates are linked. We show that
      commonly used methods, including metric-based, likelihood and Bayesian
      approaches, can have a low power to identify changes in diversification rate when
      molecular substitution rates vary. Furthermore, the association between the rates
      of speciation and molecular evolution rate can cause the signature of a slowdown
      or speedup in speciation rates to be lost or misidentified. These results suggest
      that the multiple sources of variation in molecular evolutionary rates need to be
      considered when inferring macroevolutionary processes from phylogenies.

PMID- 28758283
TI  - Copy number profiling of adult relapsed B-cell precursor acute lymphoblastic
      leukemia reveals potential leukemia progression mechanisms.
AB  - The outcome of relapsed adult acute lymphoblastic leukemia (ALL) remains dismal
      despite new therapeutic approaches. Previous studies analyzing relapse samples
      have shown a high degree of heterogeneity regarding gene alterations without an
      evident relapse signature. Bone marrow or peripheral blood samples from 31 adult
      B-cell precursor ALL patients at first relapse, and 21 paired diagnostic samples
      were analyzed by multiplex ligation probe-dependent amplification (MLPA).
      Nineteen paired diagnostic and relapse samples of these 21 patients were also
      analyzed by SNP arrays. A trend to acquire homozygous CDKN2A/B deletions and a
      significant increase in the number of copy number alterations (CNA) was observed
      from diagnosis to first relapse. Evolution from an ancestral clone was the main
      pattern of clonal evolution. Relapse samples were extremely heterogeneous
      regarding CNA frequencies. However, CDKN2A/B, PAX5, ETV6, ATM, IKZF1, VPREB1, and
      TP53 deletions and duplications of 1q, 8q, 17q, 21, X/Y PAR1, and Xp were
      frequently detected at relapse. Duplications of genes involved in cell
      proliferation, drug resistance and stem cell homeostasis regulation, as well as
      deletions of KDM6A and STAG2 genes emerged as specific alterations at relapse.
      Genomics of relapsed adult B-cell precursor ALL is highly heterogeneous, although
      some recurrent lesions involved in essential pathways deregulation were
      frequently observed. Selective and simultaneous targeting of these deregulated
      pathways may improve the results of current salvage therapies.

PMID- 28758285
TI  - Effect of ozone on the microbiological status of five dried aromatic plants.
AB  - BACKGROUND: Aromatic plants may be contaminated with a wide range of
      microorganisms, making them a potential health hazard when infused or added to
      ready-to-eat meals. To ensure safety, the effect of gaseous ozone treatment on
      the population of aerobic plate counts (APC), hygienic indicators (Escherichia
      coli, Enterococcus spp. and Enterobacteriaceae) and fungi was investigated for
      five dried aromatic plants: oregano, thyme, mountain tea, lemon verbena and
      chamomile. Selection, isolation and further fungi identification were based on
      the phenotypic and macro- and microscopic characteristics. RESULTS: Prior to
      ozonation, APC on five dried aromatic plants was in the range 5-7 log colony
      forming units (CFU) g-1 . The APC exhibited a 4 log reduction, from around 6.5 to
      2.5 in the case of oregano, and only a 1-2 log reduction for other herbs after 30
      or 60 min of 4 ppm gaseous ozone treatment. Enterococcus spp. and E. coli were
      not detected on any of the tested dried aromatic plants. The fungi counts were 2
      4 log CFU g-1 before ozonation. Aspergillus spp, Penicillium spp, Cladosporium
      spp, Alternaria spp, Fusarium spp., Ulocladium spp. and some unknown fungi were
      detected on plants before ozone treatment. Aspergillus spp. and/or Penicillium
      spp. were only detected on mountain tea and thyme plant material after 60 min of
      ozonation. CONCLUSION: The present study provides information about the
      efficiency of ozone on the microbial decontamination of dried aromatic plants.
      Treatment with gaseous ozone at 4 ppm for 30 min in the case of dried oregano and
      60 min in the case of chamomile and lemon verbena could be used as alternative
      disinfection methods. (c) 2017 Society of Chemical Industry.

PMID- 28758284
TI  - New oral anticoagulant prescription rate and risk of bleeding in an Italian
      region.
AB  - PURPOSE: The purpose of this study was to measure the prescription rate of new
      oral anticoagulants (NOACs) and to investigate whether there is an increased risk
      of bleeding associated with these medications in the 1 220 000-inhabitant Italian
      region Friuli Venezia Giulia. METHODS: The administrative data of the Regional
      Health Information System, linkable with each other at the individual patient
      level through an anonymous stochastic key, were used as the source of
      information. Prescription rates for rivaroxaban, dabigatran, and apixaban were
      calculated in the regional population in 2014 and 2015, also stratified by age
      class and gender. A case-crossover analysis with pair-matched interval approach
      and a case-time-control analysis were conducted to assess the risk of
      hospitalization with a diagnosis of bleeding and prescription of NOACs. RESULTS:
      In the regional population >=18 years of age, 1626 NOACs prescriptions per 100
      000 population-years were filled in 2014 and 3370 in 2015. Prescription rate
      increased with age and was greater in males than in females. Overall, being a
      current NOACs user was not associated with the risk of hospitalization for
      bleeding compared to being a nonuser. A nonsignificant increase in risk was
      observed among patients with low prescription intensity. CONCLUSIONS: This study
      showed an increasing time trend in NOACs prescriptions NOACs in Friuli Venezia
      Giulia. In this Italian population, NOACs users had no significantly increased
      risk of bleeding events as compared with nonusers.

PMID- 28758286
TI  - Sequential extraction of flavonoids and pectin from yellow passion fruit rind
      using pressurized solvent or ultrasound.
AB  - BACKGROUND: Passion fruit rind (PFR) represents 90% of the total fruit weight and
      is wasted during juice processing. Passion fruit rind is known to contain
      flavonoids and pectin. An alternative use for this fruit juice industrial residue
      is to obtain these compounds. This study aimed to verify the influence of
      pressurized solvent extraction (PSE) or ultrasound assisted extraction (UAE) of
      flavonoid and pectin in a sequential process. RESULTS: The PSE using ethanol at
      60:40 (v/v) yielded a total polyphenol content of 4.67 g GAE kg-1 PFR, orientin-7
      O-glucoside (1.57 g kg-1 PFR) and luteolin-6-C-glucoside (2.44 g kg-1 PFR).
      Pectin yield was 165 g kg-1 PFR, either in PSE or UAE. Pectin characterization
      indicates that the pectic structure has basically homogalacturonans and
      galacturonate followed by a galacturonic acid ester unit, with methylation degree
      of 70%. CONCLUSION: With this study it can be concluded that mixtures of alcohols
      with water favor the extraction of bioactive compounds of passion fruit peel.
      Both PSE and UAE were effective in sequentially extracting flavonoids and pectin.
      The preferred solvent is ethanol due to its lower toxicity. (c) 2017 Society of
      Chemical Industry.

PMID- 28758287
TI  - Electrophysiological correlates of the drift diffusion model in visual word
      recognition.
AB  - This study was designed to explore the electrophysiological correlates of the
      diffusion models drift rate parameter in cognitive decision making. Eighty-two
      participants completed a lexical decision task while their stimulus-dependent
      event-related potentials (ERP) and theta frequency band power were measured. A
      mass univariate approach was applied to examine the timeline at which
      correlations were evident. Individual differences in drift rate parameter and
      condition-wise within-subject differences in drift rates for word emotionality
      and item repetition were found to be related to amplitude differences in the late
      positive complex (LPC). No relations to theta frequency band power changes were
      obtained. The drift rate parameter captures information accumulation of noisy
      evidence, while LPC amplitudes are discussed to reflect the strength of a memory
      trace. While these results point to a common underlying cognitive mechanism to
      explain drift rates and LPC modulation, they also provide a new angle on the
      timeline of visual word processing following word identification. Further
      confirmations of the results are needed to approve the LPC as neurophysiological
      marker of information accumulation. Hum Brain Mapp 38:5616-5627, 2017. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28758288
TI  - Stimuli-Responsive Metal-Organic Frameworks with Photoswitchable Azobenzene Side
      Groups.
AB  - Metal-organic frameworks (MOFs) are nanoporous, crystalline hybrid materials,
      which enable various functionalities by incorporating functional organic
      molecules. By using organic linker molecules that possess photoswitchable
      azobenzene side groups, the remote control over certain properties was introduced
      to MOFs. Different MOF materials in the form of powders and thin films have been
      used to demonstrate the photoswitching. The applications of these stimuli
      responsive nanoporous solids range from switching the adsorption capacity of
      various gases over remote-controlled release of guest molecules to continuously
      tunable membrane separation of molecular mixtures. A particular focus of this
      review is the effect of the azobenzene photoswitching on the host-guest
      interaction, enabling smart applications of the material. Steric hindrance, which
      may suppress the photoswitching in some MOF structures, is also discussed.

PMID- 28758289
TI  - Changes in misuse and abuse of prescription opioids following implementation of
      Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation
      Strategy.
AB  - PURPOSE: An unintended consequence of extended-release (ER) and long-acting (LA)
      prescription opioids is that these formulations can be more attractive to abusers
      than immediate-release (IR) formulations. The US Food and Drug Administration
      recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation
      and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse
      and abuse and their associated consequences. The primary objective of this
      analysis is to determine whether ER/LA REMS implementation was associated with
      decreased reports of misuse and abuse. METHODS: Data from the Researched Abuse,
      Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center
      Program were utilized. Poison center cases are assigned a reason for exposure, a
      medical outcome, and a level of health care received. Rates adjusted for
      population and drug utilization were analyzed over time. RESULTS: RADARS System
      Poison Center Program data indicate a notable decrease in ER/LA opioid rates of
      intentional abuse and misuse as well as major medical outcomes or
      hospitalizations following implementation of the ER/LA REMS. CONCLUSIONS: While
      similar decreases were observed for the IR prescription opioid group, the
      decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR
      prescription opioids and was distinctly different than that for the prescription
      stimulants, indicating that the ER/LA REMS program may have had an additional
      effect on decreases in opioid abuse and intentional misuse beyond secular trends.

PMID- 28758290
TI  - Crystal structure of master biofilm regulator CsgD regulatory domain reveals an
      atypical receiver domain.
AB  - The master regulator CsgD switches planktonic growth to biofilm formation by
      activating synthesis of curli fimbriae and cellulose in Enterobacteriaceae. CsgD
      was classified to be the LuxR response regulatory family, while its cognate
      sensor histidine kinase has not been identified yet. CsgD consists of a C
      terminal DNA binding domain and an N-terminal regulatory domain that provokes the
      upstream signal transduction to further modulate its function. We provide the
      crystal structure of Salmonella Typhimurium CsgD regulatory domain, which reveals
      an atypical beta5alpha5 response regulatory receiver domain folding with the
      alpha2 helix representing as a disorder loop compared to the LuxR/FixJ canonical
      response regulator, and the structure indicated a noteworthy alpha5 helix similar
      to the non-canonical master regulator VpsT receiver domain alpha6. CsgD
      regulatory domain assembles with two dimerization interfaces mainly through
      alpha1 and alpha5, which has shown similarity to the c-di-GMP independent and
      stabilized dimerization interface of VpsT from Vibrio cholerae respectively. The
      potential phosphorylation site D59 is directly involved in the interaction of
      interfaces I and mutagenesis studies indicated that both dimerization interfaces
      could be crucial for CsgD activity. The structure reveals important molecular
      details for the dimerization assembly of CsgD and will shed new insight into its
      regulation mechanism.

PMID- 28758291
TI  - Xylanase production from marine derived Trichoderma pleuroticola 08CK001 strain
      isolated from Mediterranean coastal sediments.
AB  - Xylanases constitutes one the most important enzymes with diverse applications in
      different industries such as bioethanol production, animal feedstock production,
      production of xylo-oligosaccharides, baking industry, paper and pulp industry,
      xylitol production, fruit juice, and beer finishing, degumming, and agriculture.
      Currently, industrial xylanases are mainly produced by Aspergillus and
      Trichoderma members. Since the marine environments are less studied compared to
      terrestrial environments and harbors great microbial diversity we aimed to
      investigate the xylanase production of 88 marine-derived filamentous fungal
      strains. These strains are semi-quantitatively screened for their extracellular
      xylanase production and Trichoderma pleuroticola 08CK001 xylanase activity was
      further characterized. Optimum pH and temperature was determined as 5.0 and 50 
      degrees C, respectively. The enzyme preparation retained 53% of its activity at
      pH 5.0 after 1 h and have found resistant against several ions and compounds such
      as K+ , Ba2+ , Na+ , beta-mercaptoethanol, Triton X-100 and toluene. This study
      demonstrates that marine-derived fungal strains are prolific sources for xylanase
      production and presents the first report about the production and
      characterization of xylanase from a marine derived T. pleuroticola strain. The
      characteristics of T. pleuroticola 08CK001 xylanase activity indicate possible
      employment in some industrial processes such as animal feed, juice and wine
      industries or paper pulping applications.

PMID- 28758292
TI  - A psychometric evaluation of the Swedish version of the Research Utilization
      Questionnaire using a Rasch measurement model.
AB  - Evidence-based practice and research utilisation has become a commonly used
      concept in health care. The Research Utilization Questionnaire (RUQ) has been
      recognised to be a widely used instrument measuring the perception of research
      utilisation among nursing staff in clinical practice. Few studies have however
      analysed the psychometric properties of the RUQ. The aim of this study was to
      examine the psychometric properties of the Swedish version of the three subscales
      in RUQ using a Rasch measurement model. This study has a cross-sectional design
      using a sample of 163 staff (response rate 81%) working in one nursing home in
      Sweden. Data were collected using the Swedish version of RUQ in 2012. The three
      subscales Attitudes towards research, Availability of and support for research
      use and Use of research findings in clinical practice were investigated. Data
      were analysed using a Rasch measurement model. The results indicate presence of
      multidimensionality in all subscales. Moreover, internal scale validity and
      person response validity also provide some less satisfactory results, especially
      for the subscale Use of research findings. Overall, there seems to be a problem
      with the negatively worded statements. The findings suggest that clarification
      and refining of items, including additional psychometric evaluation of the RUQ,
      are needed before using the instrument in clinical practice and research studies
      among staff in nursing homes.

PMID- 28758293
TI  - Protected areas offer refuge from invasive species spreading under climate
      change.
AB  - Protected areas (PAs) are intended to provide native biodiversity and habitats
      with a refuge against the impacts of global change, particularly acting as
      natural filters against biological invasions. In practice, however, it is unknown
      how effective PAs will be in shielding native species from invasions under
      projected climate change. Here, we investigate the current and future potential
      distributions of 100 of the most invasive terrestrial, freshwater, and marine
      species in Europe. We use this information to evaluate the combined threat posed
      by climate change and invasions to existing PAs and the most susceptible species
      they shelter. We found that only a quarter of Europe's marine and terrestrial
      areas protected over the last 100 years have been colonized by any of the
      invaders investigated, despite offering climatically suitable conditions for
      invasion. In addition, hotspots of invasive species and the most susceptible
      native species to their establishment do not match at large continental scales.
      Furthermore, the predicted richness of invaders is 11%-18% significantly lower
      inside PAs than outside them. Invasive species are rare in long-established
      national parks and nature reserves, which are actively protected and often
      located in remote and pristine regions with very low human density. In contrast,
      the richness of invasive species is high in the more recently designated Natura
      2000 sites, which are subject to high human accessibility. This situation may
      change in the future, since our models anticipate important shifts in species
      ranges toward the north and east of Europe at unprecedented rates of 14-55
      km/decade, depending on taxonomic group and scenario. This may seriously
      compromise the conservation of biodiversity and ecosystem services. This study is
      the first comprehensive assessment of the resistance that PAs provide against
      biological invasions and climate change on a continental scale and illustrates
      their strategic value in safeguarding native biodiversity.

PMID- 28758294
TI  - Periodontitis: facts, fallacies and the future.
AB  - This volume of Periodontology 2000 represents the 25th anniversary of the
      Journal, and uses the occasion to assess important advancements in periodontology
      over the past quarter-century as well as the hurdles that remain. Periodontitis
      is defined by pathologic loss of the periodontal ligament and alveolar bone. The
      disease involves complex dynamic interactions among active herpesviruses,
      specific bacterial pathogens and destructive immune responses. Periodontal
      diagnostics is currently based on clinical rather than etiologic criteria, and
      provides limited therapeutic guidance. Periodontal causative treatment consists
      of scaling, antiseptic rinses and occasionally systemic antibiotics, and surgical
      intervention has been de-emphasized, except perhaps for the most advanced types
      of periodontitis. Plastic surgical therapy includes soft-tissue grafting to cover
      exposed root surfaces and bone grafting to provide support for implants. Dental
      implants are used to replace severely diseased or missing teeth, but implant
      overuse is of concern. The utility of laser treatment for periodontitis remains
      unresolved. Host modulation and risk-factor modification therapies may benefit
      select patient groups. Patient self-care is a critical part of periodontal health
      care, and twice-weekly oral rinsing with 0.10-0.25% sodium hypochlorite
      constitutes a valuable adjunct to conventional anti-plaque and anti-gingivitis
      treatments. A link between periodontal herpesviruses and systemic diseases is a
      strong biological plausibility. In summary, research during the past 25 years has
      significantly changed our concepts of periodontitis pathobiology and has produced
      more-effective and less-costly therapeutic options.

PMID- 28758295
TI  - Lasers and the treatment of periodontitis: the essence and the noise.
AB  - The dental literature contains 25 years of accumulated reports and clinical
      studies addressing the utility of lasers in the treatment of periodontitis, both
      as a monotherapy or as an adjunct to surgical and nonsurgical therapy. Yet, the
      evidence from the 118 human clinical studies cited in this narrative review
      remains conflicted and insufficient to suggest that integration of a laser in a
      periodontal treatment protocol will provide antimicrobial and healing outcomes
      superior to those achieved by traditional therapy. When viewed as a collective
      body of evidence, it becomes apparent that a majority of the studies are
      underpowered and exhibit significant heterogeneity in design. Furthermore, the
      collected studies report a varied choice of parameters, even within the same
      wavelength of laser. There is little uniformity between studies in the reporting
      of measured clinical parameters. Most studies reported 3- and/or 6-month post
      treatment results; however, the range of time intervals includes studies
      reporting results from 1 week to up to 1-12 months or longer. Lastly, many
      studies were considered at risk for bias as a result of a lack of examiner
      masking and/or calibration. There is great need for well-designed, highly
      controlled multicenter clinical trials that are adequately powered in terms of
      subject enrollment, that use similar protocols in terms of laser parameters and
      that report measureable outcomes in a uniform manner. Without such studies, the
      questions surrounding the use of lasers in the treatment of periodontal disease
      will persist.

PMID- 28758296
TI  - Failing to meet the goals of periodontal recall programs. What next?
AB  - Supportive periodontal care is a crucial aspect of the management of chronic
      periodontitis and peri-implantitis and is inevitably a long-term commitment for
      both the clinician and the patient. The principal goals of supportive care are to
      achieve a high standard of plaque control, minimize bleeding and maintain pockets
      at less than 6 mm. Gain of attachment around natural teeth during supportive
      periodontal care has been reported, although gain of attachment and of bone
      during supportive care may be a more pragmatic and aspirational aim in the longer
      term. Furthermore, we occasionally see patients for whom, despite excellent home
      and professional care (surgical or nonsurgical), including the management of risk
      factors, supportive periodontal care appears to be failing and therefore for such
      patients the clinician needs to consider further management options. This review
      considers, in particular, the options of using local or systemically delivered
      antimicrobials to eradicate periodontal and peri-implant disease progression and
      discusses the extent to which culture and sensitivity testing before the
      prescription of systemically delivered antimicrobials may be a cost-effective
      alternative to prescribing 'blind'.

PMID- 28758297
TI  - What exactly distinguishes aggressive from chronic periodontitis: is it mainly a
      difference in the degree of bacterial invasiveness?
AB  - At the International Workshop for Classification of Periodontal Diseases and
      Conditions in 1999, the classification of aggressive and chronic periodontitis
      that is presently used was introduced. A literature review of papers published in
      2015 and having aggressive periodontitis in the title revealed that most studies
      use this terminology but it is questionable whether all established criteria were
      really applied correctly. Review of the literature showed no qualitative
      differences between aggressive and chronic periodontitis regarding bacterial and
      viral aspects. It is also unlikely that that there are major immunologic
      differences between aggressive and chronic periodontitis. Neutrophil function can
      be compromised in both conditions but may be more genetically related in
      aggressive periodontitis and be associated more with lifestyle factors in chronic
      periodontitis. In general, genetics plays a more important role in aggressive
      periodontitis than in chronic periodontitis. It is likely that periodontitis
      progresses by recurrent acute episodes during which invasion of bacteria into the
      connective tissue may occur. Two cases are presented for which invasive
      periodontitis is treated with systemic antibiotics, showing remarkable
      periodontal healing in terms of probing attachment gain, as well as radiographic
      bone gain. Periodontitis in an active state with bacterial invasion is probably
      accompanied with a significant increase in subgingival temperature. It is
      hypothesized that elevated subgingival temperature may help to distinguish
      between bacterial and nonbacterial invasive periodontitis. Scaling and root
      planing during a burst of disease activity may result in removal of connective
      tissue fiber attachment and down-growth of epithelium, thereby preventing the
      reattachment of connective tissue. Because the burst of disease is accompanied by
      an increase of temperature, assessment of the temperature may help in deciding
      whether or not to prescribe systemic antibiotics. When the use of systemic
      antibiotics is indicated, the antibiotic therapy may help to maintain the
      connective tissue attachment at the most possible coronal level. The above
      implies that the ability to diagnose bacterial invasive periodontitis is quite
      important, and future research is needed to determine if assessment of
      subgingival temperature may help in diagnosing invasive periodontitis. In
      addition, it is suggested that future classification systems of periodontitis
      include the item of bacterial invasive periodontitis.

PMID- 28758298
TI  - Quo vadis: what is the future of periodontics? How will we get there?
AB  - Approximately 40 years ago periodontists began systematically developing the
      evidence to treat predictably and prevent gingivitis and periodontitis. More
      recently, periodontists have been among a small group of skilled dental-implant
      surgeons leading that revolution in dentistry. Today, much of the mild/localized
      moderate periodontitis is not treated by periodontists, and an increasing number
      of implants are placed by dentists with limited surgical training. The current
      field of periodontics includes a broad range of surgical skills and technologies
      to regenerate predictably destroyed tissues and manage complex interdisciplinary
      treatment that may, in some way, involve the tissues that support teeth and
      implants. In addition, periodontal researchers have shown that moderate-to-severe
      periodontitis increases the systemic inflammatory burden and transient
      bacteremias that result in a significant independent role for periodontitis in
      multiple systemic diseases. Although many periodontists have very advanced
      practices that incorporate certain aspects of the current and near-future
      dimensions of periodontics, the innovations and technologies have not yet fully
      integrated throughout the specialty. It is an appropriate time to ask the
      question: Quo vadis? Which paths have the potential to deliver great value to our
      patients and to the health-care system? And who will be our patients in the near
      future? We propose some key capabilities, knowledge and clinical applications.
      Perhaps most importantly, we propose new partnerships. Much of the vision centers
      around the application of special diagnostic technologies and surgical skills to
      help our dental colleagues better manage complex dental and periodontal cases and
      to deliver on the promise of reducing systemic inflammation sufficiently to
      enhance medical management of certain chronic diseases and reduce preterm births.
      The specialty has always been about retaining teeth in good health and in recent
      years has focused on controlling oral inflammation to enhance systemic health. We
      already have several of the key principles, concepts and technologies that are
      likely to define the role of periodontics in the evolving health-care delivery
      system. Perhaps it is time to define the mission and start moving toward the
      future periodontics.

PMID- 28758299
TI  - Host modulation: controlling the inflammation to control the infection.
AB  - Historically, periodontal disease (gingivitis and periodontitis) has been
      recognized as being primarily of bacterial origin. However, recent evidence
      indicates that while bacteria are necessary for disease development they are not
      sufficient for the clinical manifestation of the many and varied forms of
      periodontal disease. It is becoming increasingly apparent that it is the host
      inflammatory response to the subgingival bacteria that is responsible for the
      tissue damage and, most likely, progression of the disease. We explore the
      concept that it is the subgingival microenvironment modified by the inflammatory
      response that leads to a change from a commensal to pathogenic microbiota. In
      this review, we examine the evidence for the emerging paradigm supporting the
      central role of inflammation rather than specific microbiota in the pathogenesis
      of periodontitis, and that by controlling the inflammation, it is possible to
      control the infection. As an extension of this, we propose a working model for
      the ongoing monitoring of periodontal patients using the medical model of 'treat
      to target'.

PMID- 28758300
TI  - Nonsurgical and surgical treatment of periodontitis: how many options for one
      disease?
AB  - Treatment of periodontitis aims at preventing further disease progression with
      the intentions to reduce the risk of tooth loss, minimize symptoms and perception
      of the disease, possibly restore lost periodontal tissue and provide information
      on maintaining a healthy periodontium. Therapeutic intervention includes
      introduction of techniques to change behavior, such as: individually tailored
      oral-hygiene instructions; a smoking-cessation program; dietary adjustment;
      subgingival instrumentation to remove plaque and calculus; local and systemic
      pharmacotherapy; and various types of surgery. No single treatment option has
      shown superiority, and virtually all types of mechanical periodontal treatment
      benefit from adjunctive antimicrobial chemotherapy. Periodontal treatment,
      because of the chronic nature of periodontitis, is a lifelong commitment to
      intricate oral-hygiene techniques, which, when properly implemented, will
      minimize the risk of disease initiation and progression.

PMID- 28758301
TI  - Periodontal plastic surgery of gingival recessions at single and multiple teeth.
AB  - This manuscript aims to review periodontal plastic surgery for root coverage at
      single and multiple gingival recessions. Techniques are assessed based on
      biological principles, surgical procedures, prognosticative factors and expected
      clinical and esthetic outcomes. The use of coronally advanced flap, laterally
      sliding flap, free gingival graft, the tunnel grafting technique, barrier
      membranes, enamel matrix derivative, collagen matrix and acellular dermal matrix
      are evaluated. The clinical scenario and practical implications are analyzed
      according to a modern evidence-based approach.

PMID- 28758302
TI  - Periodontitis epidemiology: is periodontitis under-recognized, over-diagnosed, or
      both?
AB  - Currently, two principal forms of destructive periodontal disease are recognized 
      chronic periodontitis and aggressive periodontitis - but their distinction in
      epidemiologic studies has been rather problematic because of substantial overlap
      of their primary features. This review critically appraises some key features
      relevant to the epidemiology of human periodontitis that underlie its core
      'identity' as a bacterial biofilm-induced, inflammatory disease and discusses its
      impact within the larger context of aging populations. The currently adopted
      epidemiologic methodologies/definitions that result in the almost ubiquitous
      prevalence of periodontitis indeed overestimate the occurrence of the disease
      that may actually put individuals at a true biologic, functional or psychosocial
      disadvantage. Use of these definitions has inevitably promoted the inference that
      periodontitis constitutes an insurmountable oral health problem. In contrast,
      reliance solely on physical measurements of probing depth and/or attachment loss
      under-recognizes the true impact that periodontitis may have on the well-being of
      individuals. It is currently unclear whether inclusion of the psychosocial and
      systemic dimensions of the disease in case definitions would result in higher or
      lower prevalence estimates. The review concludes that periodontitis should no
      longer be defined solely by gingival/periodontal inflammation in the presence of
      increased probing depths and attachment loss but should incorporate additional
      dimensions capturing impaired function, esthetics, and impact on general health
      and quality of life. A multidimensional approach to the assessment of
      periodontitis would facilitate an improved understanding of its epidemiology and
      consequences.

PMID- 28758303
TI  - The periodontal war: microbes and immunity.
AB  - Maintenance of periodontal health or transition to a periodontal lesion reflects
      the continuous and ongoing battle between the vast microbial ecology in the oral
      cavity and the array of resident and emigrating inflammatory/immune cells in the
      periodontium. This war clearly signifies many 'battlefronts' representing the
      interface of the mucosal-surface cells with the dynamic biofilms composed of
      commensal and potential pathogenic species, as well as more recent knowledge
      demonstrating active invasion of cells and tissues of the periodontium leading to
      skirmishes in connective tissue, the locality of bone and even in the local
      vasculature. Research in the discipline has uncovered a concerted effort of the
      microbiome, using an array of survival strategies, to interact with other
      bacteria and host cells. These strategies aid in colonization by 'ambushing,
      infiltrating and outflanking' host cells and molecules, responding to local
      environmental changes (including booby traps for host biomolecules),
      communicating within and between genera and species that provide MASINT
      (Measurement and Signature Intelligence) to enhance sustained survival, sabotage
      the host inflammatory and immune responses and by potentially adopting a 'Fabian
      strategy' with a war of attrition and resulting disease manifestations.
      Additionally, much has been learned regarding the ever-increasing complexity of
      the host-response armamentarium at both cellular and molecular levels that is
      addressed in this review. Knowledge regarding how these systems fully interact
      requires both new laboratory and clinical tools, as well as sophisticated
      modeling of the networks that help maintain homeostasis and are dysregulated in
      disease. Finally, the triggers resulting in a 'coup de main' by the microbiome
      (exacerbation of disease) and the characteristics of susceptible hosts that can
      result in 'pyrrhic victories' with collateral damage to host tissues, the
      hallmark of periodontitis, remains unclear. While much has been learned,
      substantial gaps in our understanding of the 'parameters of this war' remain
      elusive toward fulfilling the Sun Tzu adage: 'If you know the enemy and know
      yourself, you need not fear the result of a hundred battles.'

PMID- 28758304
TI  - Subgingival debridement: end point, methods and how often?
AB  - Subgingival debridement is the part of nonsurgical therapy which aims to remove
      the biofilm without intentionally removing the cementum or subgingival calculus.
      The objective of this review was to describe the end point of this therapy, the
      different methods used and how often it should be carried out. The literature
      shows that several methods are currently available for subgingival debridement,
      namely hand instrumentation, (ultra)sonic instrumentation, laser, photodynamic
      therapy and air-polishing. None of these methods seems superior to any other
      regarding clinical benefits or microbiological differences. However, less
      treatment discomfort is reported using laser, photodynamic therapy or air
      polishing compared with hand- and/or (ultra)sonic instrumentation. Subgingival
      debridement can be carried out when, during supportive periodontal therapy,
      pockets of 5 mm or deeper are detected.

PMID- 28758308
TI  - Concerns regarding clinical trials in haemophilia-Augmenting Iorio's "Research
      and policy implications of a recently published controlled study in previously
      untreated haemophilia patients at high risk of inhibitor development" Haemophilia
      (2017), 1-3 https://doi.org/10.1111/hae.13176.

PMID- 28758307
TI  - Random blood glucose screening at a public health station encouraged high risk
      subjects to make lifestyle changes.
AB  - BACKGROUND: Screening and early diagnosis of prediabetes and diabetes can prevent
      or delay disease onset and complications. To that end, a free public health
      station was established in a large, government medical centre. This study
      evaluated the long-term outcomes of abnormal random blood glucose results among
      patients with no history of diabetes or prediabetes. METHODS: The Diabetes Unit
      supervised a public dysglycaemia and hypertension screening station. Participants
      with blood glucose >140 mg/dL and no history of diabetes or prediabetes were
      contacted by telephone for follow-up. RESULTS: Among screened subjects, 868
      (average age 57.5+/-12 years) had a random blood glucose level >140 mg/dL and 341
      (39.3%) responded to the telephone survey. Of these, 313 (91.8%) subsequently had
      fasting blood glucose measured at their health maintenance organisation (HMO), of
      which 101 (32.3%) were abnormal. A total of 173 (51%) respondents initiated
      interventions: 59 (17.3%) antidiabetic treatment; 145 (42.5%) sugar-restricted
      diet; and 96 (28.2%) a physical activity programme. Of patients with abnormal
      fasting blood glucose, 17 (14.5%) reported having had this result previously
      compared with 9 (4.2%) with normal fasting glucose (P=.001). Among respondents,
      216 (63.3%) stated the screening was effective and 273 (80.1%) would recommend
      it. CONCLUSION: The station was effective in promoting additional screening among
      high-risk age groups and encourages subjects to make lifestyle changes. Operating
      the screening station is simple and effective; therefore it may serve as a
      complementary step in promoting community healthcare.

PMID- 28758309
TI  - Lifestyle factors and Alzheimer's disease in people with Down syndrome.
AB  - BACKGROUND: Lifestyle has previously been associated with the onset of
      Alzheimer's disease (AD) in the typically developing population, but research
      investigating this association in Down syndrome (DS) is limited. METHOD: Adults
      with DS and AD (n = 27) were compared to adults with DS without AD (n = 30) on
      physical activity, diet, weight, where participants currently lived, where
      participants had lived for the majority of their lives, educational attainment,
      occupational attainment and cognitive activity. RESULTS: There was a significant
      difference between samples on where participants currently lived, with the
      majority of the clinical sample living in institutionalized settings and the
      majority of the control sample living in independent/supported living settings.
      This may reflect a tendency to move people once they start to deteriorate which,
      if correct, is contrary to clinical recommendations that people with AD should be
      supported to "die in place." CONCLUSIONS: Further research into the way in which
      lifestyle factors, particularly living environment, could contribute to the
      increased risk of AD in adults with DS is required. This may support
      interventions aimed at preventing or delaying the onset of the disease.

PMID- 28758306
TI  - Fear of Pain Questionnaire-9: Brief assessment of pain-related fear and anxiety.
AB  - BACKGROUND: Fear and anxiety are important considerations in both acute and
      chronic pain. Effectively and efficiently measuring fear and anxiety associated
      with pain in healthcare settings is critical for identifying vulnerable patients.
      The length and administration time of current measures of pain-related fear and
      anxiety inhibit their routine use, as screening tools and otherwise, suggesting
      the need for a shorter, more efficient instrument. METHODS: A 9-item shortened
      version of the Fear of Pain Questionnaire - III (FPQ-III), the Fear of Pain
      Questionnaire-9 (FPQ-9), was developed based upon statistical analyses of
      archival data from 275 outpatients with chronic pain and 275 undergraduates.
      Additionally, new data were collected from 100 outpatients with chronic pain and
      190 undergraduates to directly compare the standard and short forms. Exploratory
      and confirmatory factor analyses, and other psychometric analyses, were conducted
      to examine and establish the FPQ-9 as a reliable and valid instrument. RESULTS:
      The original three-factor structure of the FPQ-III was retained in the shortened
      version; a confirmatory factor analysis produced good model fit (RMSEA = 0.00,
      CFI = 1.00, TLI = 1.00, SRMR = 0.03). Results suggested a high degree of
      correlation between the original FPQ-III and the new FPQ-9 (r = 0.77, p < 0.001).
      Measures of internal consistency for FPQ-9 subscales were high; correlations with
      other pain and anxiety instruments suggested concurrent, convergent and divergent
      validity. CONCLUSIONS: The FPQ-9 is a psychometrically sound alternative to
      longer instruments assessing fear and anxiety associated with pain, for use in
      both clinical and research situations that only allow brief screening.
      SIGNIFICANCE: The FPQ-9 has considerable potential for dissemination and utility
      for routine, brief screening, given its length (completion time ~2 min; scoring
      time ~1 min), reading level and psychometric properties.

PMID- 28758310
TI  - The global burden of respiratory infections in indigenous children and adults: A
      review.
AB  - This review article focuses on common lower respiratory infections (LRIs) in
      indigenous populations in both developed and developing countries, where data is
      available. Indigenous populations across the world share some commonalities
      including poorer health and socio-economic disadvantage compared with their non
      indigenous counterparts. Generally, acute and chronic respiratory infections are
      more frequent and more severe in both indigenous children and adults, often
      resulting in substantial consequences including higher rates of bronchiectasis
      and poorer outcomes for patients with chronic obstructive pulmonary disease
      (COPD). Risk factors for the development of respiratory infections require
      recognition and action. These risk factors include but are not limited to socio
      economic factors (e.g. education, household crowding and nutrition),
      environmental factors (e.g. smoke exposure and poor access to health care) and
      biological factors. Risk mitigation strategies should be delivered in a
      culturally appropriate manner and targeted to educate both individuals and
      communities at risk. Improving the morbidity and mortality of respiratory
      infections in indigenous people requires provision of best practice care and
      awareness of the scope of the problem by healthcare practitioners, governing
      bodies and policy makers.

PMID- 28758311
TI  - Was it less painful for knights? Influence of appearance on pain perception.
AB  - BACKGROUND: Pain perception is a subjective experience shaped by different
      factors. In this study, we investigated the influence of a visually manipulated
      appearance of a virtual arm on pain perception. Specifically, we investigated how
      pain perception and vegetative skin responses were modified by inducing a virtual
      protection on the right arm by a virtual armour. METHODS: Participants (n = 32)
      immersed in virtual reality embodied a virtual arm, which appeared in three
      different versions (uncovered, neutral or protected). During the virtual reality
      simulation, the participants received electrical stimulations of varying
      intensities. Skin conductance level (SCL) was analysed for the phase anticipation
      (from the moment the arm appeared until the electric stimulation) and perception
      of pain (after the electric stimulation). Pain ratings were acquired after the
      painful stimuli occurred. RESULTS: The sense of embodiment was positive for the
      unprotected and neutral condition and lower for the protected than for the
      neutral arm. Pain ratings were significantly decreased in the protected arm
      condition compared with both the unprotected arm and the neutral arm conditions.
      The SCL measurements showed no significant differences for the three arm types.
      CONCLUSIONS: According to the pain ratings, participants felt significantly less
      pain in the covered arm condition compared with the unprotected and the neutral
      arm condition. Subjective pain perception was decreased by a virtual protection
      of the arm in VR. The simplicity of the manipulation suggests possible practical
      uses in pain therapy by strengthening the patients' own capacities to influence
      their pain using simple cognitive manipulations via virtual reality.
      SIGNIFICANCE: A virtual, covered arm causes differences in reported pain ratings.
      Physiological measurements do not confirm the findings. Visual information about
      body protection can have an impact on pain perception.

PMID- 28758312
TI  - Testing the validity of telephone interviews to assess chronic pain in children
      and adolescents: A randomized cross-over trial.
AB  - BACKGROUND: Telephone surveys are intended to reduce attrition in longitudinal
      studies. For paediatric chronic pain patients, the comparability of pain-related
      information gathered using telephone interviews and postal surveys remain
      unknown. Furthermore, it remains unknown how social desirability may influence
      answers. METHODS: To compare data from telephone interviews and postal surveys, a
      randomized cross-over design with two measure points 2 weeks apart and four
      conditions (combinations of telephone interviews (T) and postal surveys (P): P-T,
      T-P, P-P, T-T) was conducted in a sample of N = 323 paediatric chronic pain
      patients. RESULTS: In the inter-group comparison, pain-related information did
      not differ between telephone interviews and postal surveys except for the
      information on pain location (back and extremities). Agreement measures of the
      intra-group comparisons suggest substantial to excellent agreements for all items
      and did not differ between the groups. The internal consistency of a disability
      scale was excellent for both assessment modes; the number of missing values did
      not differ. Participation rate was higher for telephone interviews compared to
      the postal surveys. Across both time points, attrition was lowest for the groups
      without a switch in assessment mode compared to the groups with a switch in
      assessment mode. Except for pain-related school absence, no effect of social
      desirability occurred. CONCLUSIONS: Telephone interviews are a useful method to
      achieve a high response rate. Pain locations should be asked for separately and
      not in an open question when interviewing children and adolescents on the
      telephone. SIGNIFICANCE: Telephone interviews are a good method to achieve a high
      response rate and obtain valid data in studies with paediatric chronic pain
      patients.

PMID- 28758305
TI  - Revisiting the Page & Schroeder model: the good, the bad and the unknowns in the
      periodontal host response 40 years later.
AB  - In their classic 1976 paper, Page & Schroeder described the histopathologic
      events and the types of myeloid cells and lymphocytes involved in the initiation
      and progression of inflammatory periodontal disease. The staging of periodontal
      disease pathogenesis as 'initial', 'early', 'established' and 'advanced' lesions
      productively guided subsequent research in the field and remains fundamentally
      valid. However, major advances regarding the cellular and molecular mechanisms
      underlying the induction, regulation and effector functions of immune and
      inflammatory responses necessitate a reassessment of their work and its
      integration with emerging new concepts. We now know that each type of leukocyte
      is actually represented by functionally distinct subsets with different, or even
      conflicting, roles in immunity and inflammation. Unexpectedly, neutrophils,
      traditionally regarded as merely antimicrobial effectors in acute conditions and
      protagonists of the 'initial' lesion, are currently appreciated for their
      functional versatility and critical roles in chronic inflammation. Moreover, an
      entirely new field of study, osteoimmunology, has emerged and sheds light on the
      impact of immunoinflammatory events on the skeletal system. These developments
      and the molecular dissection of crosstalk interactions between innate and
      adaptive leukocytes, as well as between the immune system and local homeostatic
      mechanisms, offer a more nuanced understanding of the host response in
      periodontitis, with profound implications for treatment. At the same time, deeper
      insights have generated new questions, many of which remain unanswered. In this
      review, 40 years after Page & Schroeder proposed their model, we summarize
      enduring and emerging advances in periodontal disease pathogenesis.

PMID- 28758313
TI  - Altered theta oscillations in resting EEG of fibromyalgia syndrome patients.
AB  - BACKGROUND: Fibromyalgia syndrome (FM) is a chronic pain disorder characterized
      by widespread pain, sleep disturbance, fatigue and cognitive/affective symptoms.
      Functional imaging studies have revealed that FM and other chronic pain syndromes
      can affect resting brain activity. This study utilized electroencephalographic
      (EEG) recordings to investigate the relative power of ongoing oscillatory
      activity in the resting brain. METHODS: A 64-channel EEG was recorded at rest in
      19 female FM patients and 18 healthy, age-matched, control subjects. The Manual
      Tender Point Scale (MTPS) examination was performed to quantify tonic pain and
      tenderness on the day of testing along with measures of mood, arousal and
      fatigue. Oscillations in delta, theta, alpha, beta and gamma frequency bands were
      analysed using Standardised Low-Resolution Brain Electromagnetic Tomography to
      evaluate sources of spectral activity throughout the whole brain. RESULTS: FM
      patients exhibited greater pain, tiredness and tension on the day of testing
      relative to healthy control participants and augmented theta activity in
      prefrontal and anterior cingulate cortices. No significant differences were seen
      in other frequency bands. Augmented frontal theta activity in FM patients
      significantly correlated with measures of tenderness and mean tiredness scores.
      CONCLUSIONS: The findings indicate that alterations to resting-state oscillatory
      activity may relate to ongoing tonic pain and fatigue in FM, and manifest in
      brain regions relevant for cognitive-attentional aspects of pain processing and
      endogenous pain inhibition. Enhanced low-frequency oscillations were previously
      seen in FM and other chronic pain syndromes, and may relate to pathophysiological
      mechanisms for ongoing pain such as thalamocortical dysrhythmia. SIGNIFICANCE:
      Increased prefrontal theta activity may contribute to persistent pain in
      fibromyalgia or represent the outcome of prolonged symptoms. The findings point
      to the potential for therapeutic interventions aimed at normalizing neural
      oscillations, while further research utilizing quantitative analysis of resting
      EEG could benefit our understanding of fibromyalgia pathophysiology.

PMID- 28758314
TI  - Child and parental executive functioning in type 1 diabetes: Their unique and
      interactive role toward treatment adherence and glycemic control.
AB  - OBJECTIVE: Managing type 1 diabetes (T1D) requires the ability to make complex
      and critical decisions regarding treatment, to execute complex tasks accurately,
      and to make adjustments when problems arise. This requires effective
      neuropsychological competences of patients and their families, especially in the
      domain of executive functioning (EF): the ability to self-monitor, plan, solve
      problems, and set priorities. Previous research focused mainly on child EF,
      neglecting the impact of parental EF. This study included both mothers and
      fathers and examined associations between child and parental EF and treatment
      adherence to T1D in a broad age range of patients. METHODS: Parents of 270
      patients (6-18 years) with T1D (mean age 12.7 years; 52.6% female) were included.
      Mothers (N = 232) and fathers (N = 168) completed questionnaires on child and
      parental EF and on treatment adherence. Analyses examined the associations
      linking child and parental EF to treatment adherence and glycemic control (and
      potential moderation effects in these associations) using hierarchical linear
      regression. RESULTS: Child EF problems were negatively associated with treatment
      adherence. As an indication of moderation, this effect was stronger in older
      children. Better treatment adherence and glycemic control were reported when both
      child and parent showed less EF problems. Effects were more pronounced in mothers
      than in fathers. CONCLUSIONS: This study demonstrated a significant interplay
      between child and parental EF in the association with treatment adherence and
      glycemic control. Researchers and clinicians should remain attentive toward the
      role of neuropsychological concepts such as EF. Implementation in clinical
      practice seems meaningful.

PMID- 28758315
TI  - Acanthosis Nigricans and Its Response to Metformin.
AB  - Acanthosis nigricans (AN) is the most common cutaneous manifestation of insulin
      resistance (IR) and is commonly seen in non-Caucasian populations. Variable
      benefits of metformin in the treatment of AN have been reported in the
      literature. We report an adolescent Caucasian boy with IR and extensive AN who
      showed complete resolution of AN after 2 years of metformin, despite persistence
      of IR.

PMID- 28758316
TI  - Multivitamin use and risk of stroke incidence and mortality amongst women.
AB  - BACKGROUND AND PURPOSE: Few studies have examined the association between
      multivitamin use and the risk of stroke incidence and mortality, and the results
      remain inconclusive as to whether multivitamins are beneficial. METHODS: The
      associations between multivitamin use and the risk of incident stroke and stroke
      mortality were prospectively examined in 86 142 women in the Nurses' Health
      Study, aged 34-59 years and free of diagnosed cardiovascular disease at baseline.
      Multivitamin use and covariates were updated every 2 years and strokes were
      documented by review of medical records. Hazard ratios of total, ischaemic and
      hemorrhagic strokes were calculated across categories of multivitamin use (non
      user, past, current user) and duration (years), using Cox proportional hazards
      models. RESULTS: During 32 years of follow-up from 1980 to 2012, 3615 incident
      strokes were documented, including 758 deaths from stroke. In multivariate
      analyses, women who were current multivitamin users did not have a lower risk of
      incident total stroke compared to non-users [relative risk (RR) 1.02, 95%
      confidence interval (CI) 0.93-1.11], even those with longer durations of 15 or
      more years of use (RR 1.08, 95% CI 0.97-1.20) or those with a lower quality diet
      (RR 0.96, 95% CI 0.80-1.15). There was also no indication of benefit from
      multivitamin use for incident ischaemic or hemorrhagic strokes or for total
      stroke mortality. CONCLUSIONS: Long-term multivitamin use was not associated with
      reduced risk of stroke incidence or mortality amongst women in the study
      population, even amongst those with a lower diet quality. An effect in a less
      well-nourished population cannot be ruled out.

PMID- 28758317
TI  - Eccrine Chromhidrosis in an Adolescent with Sickle Cell Disease.
AB  - Eccrine chromhidrosis can occur secondary to hyperbilirubinemia. We report an
      adolescent with sickle cell disease who presented with eccrine chromhidrosis on
      his palmar and plantar surfaces. He had extremely high levels of conjugated
      bilirubin but no fever. This is the youngest known reported patient with eccrine
      chromhidrosis and the first in a patient with sickle cell disease.

PMID- 28758318
TI  - The role of neurotransmitters in the development of Parkinson's disease-related
      psychosis.
AB  - Psychotic symptoms are common, disabling non-motor features of Parkinson's
      disease (PD). Despite noted heterogeneity in clinical features, natural history
      and therapy response, current dogma posits that psychosis generally progresses in
      a stereotypic manner through a cascade of events that begins with minor
      hallucinations and evolves to severe hallucinations and delusions. Further, the
      occurrence of psychotic symptoms is believed to indicate a poor prognosis. Here
      we propose a classification scheme that outlines the pathogenesis of psychosis as
      it relates to dysfunction of several neurotransmitter systems. We hypothesize
      that several subtypes exist, and that PD psychosis is not consistently indicative
      of a progressive cascade and poor prognosis. The literature was reviewed from
      1990 to 2017. An overview of the features of PD psychosis is followed by a review
      of data indicating the existence of neurotransmitter-related subtypes of
      psychosis. We found that ample evidence exists to demonstrate the presence of
      multiple subtypes of PD psychosis, which are traced to dysfunction of the
      following neurotransmitter systems: dopamine, serotonin and acetylcholine.
      Dysfunction of each of these systems is recognizable through their clinical
      features and correlates, and the varied long-term prognoses. Identifying which
      neurotransmitter system is dysfunctional may help to develop targeted therapies.
      PD psychosis has various subtypes that differ in clinical features, underlying
      pathology and pathophysiology, treatment response and prognosis. A novel
      classification scheme is presented that describes the clinical subtypes with
      different outcomes, which could lead to the development of targeted therapies.
      Future research should focus on testing the viability of this classification.

PMID- 28758319
TI  - Treatment options for unresectable HCC with a focus on SIRT with Yttrium-90 resin
      microspheres.
AB  - : Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer,
      is the second leading cause of cancer-related deaths across the globe. Only a
      small percentage of HCC patients (~20%-30%) are diagnosed at an early stage when
      first-line treatment options may be effective. The majority of HCC patients
      (>70%) are diagnosed with unresectable disease and given a poor overall
      prognosis. Current treatment guidelines recommend locoregional therapy with
      transarterial chemoembolisation (TACE) and systemic therapy with sorafenib as
      first-line treatment for patients with intermediate and advanced stage HCC.
      However, multiple factors including contraindications, technical considerations
      and treatment-related toxicities pose significant challenges in achieving
      favourable treatment outcomes, underscoring the need for a paradigm shift in
      managing these patients. In 2002, yttrium-90 (Y-90) resin microspheres was
      approved by the U.S. Food and Drug Administration (FDA) for the treatment of
      unresectable metastatic colorectal cancer to the liver with adjuvant floxuridine
      chemotherapy. However, thousands of patients with unresectable HCC have also been
      treated with resin Y-90. For over two decades, several small-scale prospective
      trials and retrospective studies have investigated and reported on the efficacy
      of locoregional selective internal radiation therapy (SIRT) with Y-90
      microspheres in treating unresectable HCC. Although it is currently a treatment
      option for intermediate-stage HCC patients, mainstream clinical application of
      resin Y-90 has been largely limited because of the lack of sufficient clinical
      data from a randomised controlled trial. This could change with the imminent
      announcement of results from the phase 3 Sorafenib vs Radioembolization in
      Advanced Hepatocellular carcinoma (SARAH) trial. To provide the foundation and
      context for interpreting results from the SARAH trial, this article provides an
      overview of treatment modalities and current challenges in managing unresectable
      HCC. There is also a review of key prospective and retrospective studies
      evaluating the use of Y-90 SIRT, specifically Y-90 resin microspheres in
      unresectable HCC, which led to the development of the SARAH trial. METHODS: To
      identify relevant publications, the PubMed database was queried using one or more
      of the following search terms alone or in combination with Boolean operators:
      epidemiology, hepatocellular, hepatocellular cancer, hepatocellular carcinoma,
      unresectable, radioembolisation, selective internal radiation therapy, SIR
      Spheres, yttrium 90, TACE, and sorafenib. The results were sorted or filtered by
      "Author", "Publication dates" or "Article types" to identify articles relevant to
      each section of the review. To ensure that information on ongoing clinical trials
      involving Y-90 resin was included, we conducted a search on "ClinicalTrials.gov",
      by combining the search terms "HCC" OR "hepatocellular carcinoma" with "Y 90" OR
      "yttrium 90" OR "radioembo", and screened for studies that involved treatment
      with Y-90 resin microspheres.

PMID- 28758320
TI  - Effect on health-related quality of life of ongoing feedback during a 12-month
      maintenance walking programme in patients with COPD: a randomized controlled
      trial.
AB  - BACKGROUND AND OBJECTIVE: In patients with COPD, this study evaluated the effect
      on health-related quality of life (HRQoL) of adding ongoing feedback to a 12
      month unsupervised maintenance walking programme. METHODS: Participants were
      randomized to either an intervention group (IG) or control group (CG). Both
      groups completed the same 2-month supervised, walking training programme followed
      by a 12-month unsupervised maintenance walking programme. During the maintenance
      programme, the IG received ongoing feedback (telephone calls, biofeedback and
      progressive goal setting) and the CG received no feedback. RESULTS: A total of 75
      participants completed the study (mean (SD): age 69 (8) years; forced expiratory
      volume in 1 s (FEV1 ) 43 (15) % predicted). There was no between-group
      differences in the magnitude of change in HRQoL when data collected on completion
      of the 12-month maintenance programme were compared with that collected either
      before the 2-month supervised programme (mean between-group difference (MD) in
      total St George's Respiratory Questionnaire change scores: 1 point, 95% CI: -9 to
      7) or on completion of the 2-month supervised programme (MD: 4 points, 95% CI -2
      to 10). CONCLUSION: Following a 2-month supervised walking training programme,
      ongoing feedback was no more effective than no feedback in maintaining HRQoL
      during a 12-month unsupervised walking programme.

PMID- 28758321
TI  - Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in
      Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage.
AB  - Limbal stem cells are responsible for the continuous renewal of the corneal
      epithelium. The destruction or dysfunction of these stem cells or their niche
      induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain,
      and inflammation of the ocular surface. To restore the ocular surface in cases of
      bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence
      on allogeneic limbal stem cells that are difficult to obtain, isolate, and
      culture. The aim of this work was to test the tolerance and the efficacy of human
      adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular
      surface in two experimental models of LSCD that closely resemble different
      severity grades of the human pathology. hAT-MSCs transplanted to the ocular
      surface of the partial and total LSCD models developed in rabbits were well
      tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the
      evolution of corneal neovascularization and corneal opacity. The expression
      profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal
      epithelial cell markers CK15 and p63 was lost in the LSCD models, but was
      partially recovered after hAT-MSC transplantation. For the first time, we
      demonstrated that hAT-MSCs improve corneal and limbal epithelial phenotypes in
      animal LSCD models. These results support the potential use of hAT-MSCs as a
      novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an
      available, non-immunogenic source of stem cells that may provide therapeutic
      benefits in addition to reduce health care expenses. Stem Cells 2017;35:2160
      2174.

PMID- 28758323
TI  - Debate article: Antipsychotic medications are clinically useful for the treatment
      of delirium.
AB  - Prescribing of antipsychotic medications for patients with delirium remains
      controversial. Concerns exist that these vulnerable and frail patients may be
      prescribed antipsychotics inappropriately as a substitute for non-pharmacological
      approaches when identifiable causes are not found or they challenge ward
      processes. Moreover, recent evidence suggests that antipsychotics may cause more
      harm than good in the palliative care patient group with delirium. On the other
      hand, guidelines in the United Kingdom and the Netherlands support prescribing of
      antipsychotics in certain circumstances, and a large European survey has revealed
      that antipsychotics tend to be prescribed first line for hyperactive delirium.
      Never before, therefore, is there a greater need to examine whether indeed these
      medications are clinically useful for the treatment of delirium. With this in
      mind, evidence-based arguments for and against prescribing antipsychotics for the
      treatment of delirium are presented in this debate article. The paper concludes
      with a moderation piece to help guide clinical practice.

PMID- 28758322
TI  - Smallest detectable change and test-retest reliability of a self-reported outcome
      measure: Results of the Center for Epidemiologic Studies Depression Scale,
      General Self-Efficacy Scale, and 12-item General Health Questionnaire.
AB  - RATIONALE, AIMS, AND OBJECTIVES: This study aims to examine the smallest
      detectable change (SDC) and test-retest reliability of the Center for
      Epidemiologic Studies Depression Scale (CES-D), General Self-Efficacy Scale
      (GSES), and 12-item General Health Questionnaire (GHQ-12). METHOD: We tested 154
      young adults at baseline and 2 weeks later. We calculated the intra-class
      correlation coefficients (ICCs) for test-retest reliability with a two-way random
      effects model for agreement. We then calculated the standard error of measurement
      (SEM) for agreement using the ICC formula. The SEM for agreement was used to
      calculate SDC values at the individual level (SDCind ) and group level (SDCgroup
      ). RESULTS: The study participants included 137 young adults. The ICCs for all
      self-reported outcome measurement scales exceeded 0.70. The SEM of CES-D was
      3.64, leading to an SDCind of 10.10 points and SDCgroup of 0.86 points. The SEM
      of GSES was 1.56, leading to an SDCind of 4.33 points and SDCgroup of 0.37
      points. The SEM of GHQ-12 with bimodal scoring was 1.47, leading to an SDCind of
      4.06 points and SDCgroup of 0.35 points. The SEM of GHQ-12 with Likert scoring
      was 2.44, leading to an SDCind of 6.76 points and SDCgroup of 0.58 points.
      CONCLUSION: To confirm that the change was not a result of measurement error, a
      score of self-reported outcome measurement scales would need to change by an
      amount greater than these SDC values. This has important implications for
      clinicians and epidemiologists when assessing outcomes.

PMID- 28758324
TI  - Surgery and survival in birth cohorts with severe haemophilia and differences in
      access to replacement therapy: The Malmo experience.
AB  - BACKGROUND: Persons with severe haemophilia require lifelong replacement therapy,
      prophylaxis, to prevent bleeding. Data describing long-term outcomes of
      prophylactic treatment are scarce. The aim of this study was to investigate joint
      surgery and survival among persons with severe haemophilia with special attention
      to access to prophylaxis in the early years of life. METHODS: Eligible
      participants had severe haemophilia A or B and were treated at the Malmo centre
      from the 1960s onward. Time from birth until joint surgery was analysed for
      participants negative for factor inhibitor and alive in 2000. We compared
      survival among the entire cohort with severe haemophilia treated at the Malmo
      centre with the general male population of Sweden and a sample of persons with
      severe haemophilia from the United Kingdom (UK). RESULTS: Overall, 167
      participants were included, 106 (63.5%) of whom had complete data on joint
      surgery. Among those born before 1970, 1970-1979 and >=1980 approximately 37%,
      21% and 0% had their first joint surgery by age 30, respectively. There were no
      second joint surgeries reported in cohorts born >=1970. Persons with severe
      haemophilia and negative for HIV treated in Malmo have attained approximately
      similar survival to that of the general male population in Sweden and live
      slightly longer than persons with severe haemophilia from the UK. DISCUSSION AND
      CONCLUSION: Prophylaxis in Sweden, although costly, has markedly improved
      survival and joint outcomes for persons with severe haemophilia. This study
      highlights the importance of early start of replacement therapy to prevent or
      postpone serious joint damage.

PMID- 28758325
TI  - Community-acquired pneumonia management and outcomes in the era of health
      information technology.
AB  - Pneumonia continues to be a leading cause of hospitalization and mortality.
      Implementation of health information technology (HIT) can lead to cost savings
      and improved care. In this review, we examine the literature on the use of HIT in
      the management of community-acquired pneumonia. We also discuss barriers to
      adoption of technology in managing pneumonia, the reliability and quality of
      electronic health data in pneumonia research, how technology has assisted
      pneumonia diagnosis and outcomes research. The goal of using HIT is to develop
      and deploy generalizable, real-time, computerized clinical decision support
      integrated into usual pneumonia care. A friendly user interface that does not
      disrupt efficiency and demonstrates improved clinical outcomes should result in
      widespread adoption.

PMID- 28758326
TI  - A novel optimal coordinated control strategy for the updated robot system for
      single port surgery.
AB  - BACKGROUND: Research into robotic systems for single port surgery (SPS) has
      become widespread around the world in recent years. A new robot arm system for
      SPS was developed, but its positioning platform and other hardware components
      were not efficient. Special features of the developed surgical robot system make
      good teleoperation with safety and efficiency difficult. METHODS: A robot arm is
      combined and used as new positioning platform, and the remote center motion is
      realized by a new method using active motion control. A new mapping strategy
      based on kinematics computation and a novel optimal coordinated control strategy
      based on real-time approaching to a defined anthropopathic criterion
      configuration that is referred to the customary ease state of human arms and
      especially the configuration of boxers' habitual preparation posture are
      developed. RESULTS: The hardware components, control architecture, control
      system, and mapping strategy of the robotic system has been updated. A novel
      optimal coordinated control strategy is proposed and tested. CONCLUSIONS: The new
      robot system can be more dexterous, intelligent, convenient and safer for
      preoperative positioning and intraoperative adjustment. The mapping strategy can
      achieve good following and representation for the slave manipulator arms. And the
      proposed novel control strategy can enable them to complete tasks with higher
      maneuverability, lower possibility of self-interference and singularity free
      while teleoperating.

PMID- 28758327
TI  - Characterization of PVA/glutaraldehyde hydrogels obtained using Central Composite
      Rotatable Design (CCRD).
AB  - Hydrogels are made from natural or synthetic polymers and, currently, they have
      many biomedical applications. In this work, the conditions for obtaining a
      hydrogel with similar physicochemical characteristics to the vitreous humor were
      defined using polyvinyl alcohol (PVA) and glutaraldehyde (GLUT) as cross-linker.
      The concentration of PVA and GLUT were modified, and their effect was analyzed in
      terms of the refractive index, density, and dynamic viscosity. The hydrogel which
      was obtained using 3.98% (w/V) of PVA, 3.13 mL (1.57 g) of GLUT in 100 mL, and
      the initial pH of 7.2 showed similar characteristics to the vitreous humor
      (density = 1.0174 +/- 0.0050 g mL-1 , dynamic viscosity = 3.7425 +/- 0.1800 mPa s
      and refractive index = 1.3410 +/- 0.0010). The hydrogels were further
      investigated by rheological measurements, infrared spectroscopy, differential
      scanning calorimetry, X-ray diffraction and determination of swelling degree. The
      reticulation with GLUT promoted an increase in viscosity and glass transition
      temperature. On the other hand, it stimulated a decrease in the swelling degree,
      crystallinity, melting temperature, and intensity of the band related to the -OH
      bond, compared with the PVA without reticulation. The reticulated hydrogel
      displayed Newtonian behavior and a higher apparent viscosity than the PVA. (c)
      2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1558
      1566, 2018.

PMID- 28758329
TI  - Kidney allograft offers: Predictors of turndown and the impact of late organ
      acceptance on allograft survival.
AB  - There is growing interest in understanding patterns of organ acceptance and
      reducing discard. Little is known about how donor factors, timing of procurement,
      and geographic location affect organ offer decisions. We performed a
      retrospective cohort study of 47 563 deceased donor kidney match-runs from 2007
      to 2013. Several characteristics unrelated to allograft quality were
      independently associated with later acceptance in the match-run: Public Health
      Service increased-risk donor status (adjusted odds ratio [aOR] 2.49, 95%
      confidence interval [CI] 2.29-2.69), holiday or weekend procurement (aOR 1.11,
      95% CI 1.07-1.16), shorter donor stature (aOR 1.53 for <150 cm vs reference >180
      cm, 95% CI 1.28-1.94), and procurement in an area with higher intensity of market
      competition (aOR 1.71, 95% CI 1.62-1.78) and with the longest waiting times (aOR
      1.41, 95% CI 1.34-1.49). Later acceptance in the match-run was associated with
      delayed graft function but not all-cause allograft failure (adjusted hazard ratio
      1.01, 95% CI 0.96-1.07). Study limitations include a lack of match-run data for
      discarded organs and the possibility of sequence inaccuracies for some nonlocal
      matches. Interventions are needed to reduce turndowns of viable organs,
      especially when decisions are driven by infectious risk, weekend or holiday
      procurement, geography, or other donor characteristics unrelated to allograft
      quality.

PMID- 28758330
TI  - Thermo-physical properties of synthetic mucus for the study of airway clearance.
AB  - In this article, dynamic viscosity, surface tension, density, heat capacity and
      thermal conductivity, of a bronchial mucus simulant proposed by Zahm et al., Eur
      Respir J 1991; 4: 311-315 were experiementally determined. This simulant is
      mainly composed of a galactomannan gum and a scleroglucan. It was shown that
      thermophysical properties of synthetic mucus are dependant of scleroglucan
      concentrations. More importantly and for some scleroglucan concentrations, the
      syntetic mucus, exhibits, somehow, comparable thermophysical properties to real
      bronchial mucus. An insight on the microstructure of this simulant is proposed
      and the different properties enounced previously have been measured for various
      scleroglucan concentrations and over a certain range of operating temperatures.
      This synthetic mucus is found to mimic well the rheological behavior and the
      surface tension of real mucus for different pathologies. Density and thermal
      properties have been measured for the first time. (c) 2017 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 105A: 3025-3033, 2017.

PMID- 28758331
TI  - Global kidney exchange: Financially incompatible pairs are not transplantable
      compatible pairs.

PMID- 28758332
TI  - A biosafety level 2 virology lab for biotechnology undergraduates.
AB  - Medical, industrial, and basic research relies heavily on the use of viruses and
      vectors. Therefore, it is important that bioscience undergraduates learn the
      practicalities of handling viruses. Teaching practical virology in a student
      laboratory setup presents safety challenges, however. The aim of this article is
      to describe the design and implementation of a virology laboratory, with emphasis
      on student safety, for biotechnology undergraduates. Cell culture techniques,
      animal virus infection, quantification, and identification are taught at a
      biosafety level 2 for a diverse group of undergraduates ranging from 20 to 50
      students per group. (c) 2017 by The International Union of Biochemistry and
      Molecular Biology, 45(6):537-543, 2017.

PMID- 28758328
TI  - The path from mitochondrial ROS to aging runs through the mitochondrial
      permeability transition pore.
AB  - Excessive production of mitochondrial reactive oxygen species (mROS) is strongly
      associated with mitochondrial and cellular oxidative damage, aging, and
      degenerative diseases. However, mROS also induces pathways of protection of
      mitochondria that slow aging, inhibit cell death, and increase lifespan. Recent
      studies show that the activation of the mitochondrial permeability transition
      pore (mPTP), which is triggered by mROS and mitochondrial calcium overloading, is
      enhanced in aged animals and humans and in aging-related degenerative diseases.
      mPTP opening initiates further production and release of mROS that damage both
      mitochondrial and nuclear DNA, proteins, and phospholipids, and also releases
      matrix NAD that is hydrolyzed in the intermembrane space, thus contributing to
      the depletion of cellular NAD that accelerates aging. Oxidative damage to calcium
      transporters leads to calcium overload and more frequent opening of mPTP. Because
      aging enhances the opening of the mPTP and mPTP opening accelerates aging, we
      suggest that mPTP opening drives the progression of aging. Activation of the mPTP
      is regulated, directly and indirectly, not only by the mitochondrial protection
      pathways that are induced by mROS, but also by pro-apoptotic signals that are
      induced by DNA damage. We suggest that the integration of these contrasting
      signals by the mPTP largely determines the rate of cell aging and the initiation
      of cell death, and thus animal lifespan. The suggestion that the control of mPTP
      activation is critical for the progression of aging can explain the conflicting
      and confusing evidence regarding the beneficial and deleterious effects of mROS
      on health and lifespan.

PMID- 28758333
TI  - Topotactic Metal-Insulator Transition in Epitaxial SrFeOx Thin Films.
AB  - Topotactic phase transformation enables structural transition without losing the
      crystalline symmetry of the parental phase and provides an effective platform for
      elucidating the redox reaction and oxygen diffusion within transition metal
      oxides. In addition, it enables tuning of the emergent physical properties of
      complex oxides, through strong interaction between the lattice and electronic
      degrees of freedom. In this communication, the electronic structure evolution of
      SrFeOx epitaxial thin films is identified in real-time, during the progress of
      reversible topotactic phase transformation. Using real-time optical spectroscopy,
      the phase transition between the two structurally distinct phases (i.e.,
      brownmillerite and perovskite) is quantitatively monitored, and a pressure
      temperature phase diagram of the topotactic transformation is constructed for the
      first time. The transformation at relatively low temperatures is attributed to a
      markedly small difference in Gibbs free energy compared to the known similar
      class of materials to date. This study highlights the phase stability and
      reversibility of SrFeOx thin films, which is highly relevant for energy and
      environmental applications exploiting the redox reactions.

PMID- 28758334
TI  - 31 P NMR of the pyruvate kinase reaction: An undergraduate experiment in enzyme
      kinetics.
AB  - Understanding how to perform an enzyme assay is a critical learning skill in the
      undergraduate biochemistry curriculum. Students in biochemistry typically have
      been exposed to the use of NMR spectroscopy as a tool to determine chemical
      structure, but rarely are they exposed to the utility of NMR to evaluate enzyme
      kinetics. Furthermore, coverage of NMR experiments utilizing "alternative
      nuclei", such as 15 N, 19 F, and 31 P may be neglected. Herein we report a simple
      31 P NMR tube experiment that allows students to examine the enzyme kinetics and
      equilibrium constant of the reaction catalyzed by pyruvate kinase. (c) 2017 by
      The International Union of Biochemistry and Molecular Biology, 45(6):509-514,
      2017.

PMID- 28758336
TI  - Dual-graft adult living donor liver transplantation with ABO-incompatible graft:
      short-term and long-term outcomes.
AB  - ABO-incompatible (ABOi) dual-graft (DG) adult living donor liver transplantation
      (ALDLT) is not commonly performed due to its inherently intricate surgical
      technique and immunological complexity. Therefore, data are lacking on the short-
      and long-term clinical outcomes of ABOi DG ALDLT. We performed a retrospective
      study by reviewing the medical records of patients who underwent ABOi DG ALDLT
      between 2008 and 2014. Additionally, computed tomography volumetric analysis was
      conducted to assess the graft regeneration rate. The mean age of a total of 28
      recipients was 50.2 +/- 8.5 years, and the mean model for end-stage liver disease
      score was 12.2 +/- 4.6. The 1-, 3-, and 5-year patient survival rate was 96.4%
      during the mean follow-up period of 57.0 +/- 22.4 months. The 1-, 3-, and 5-year
      graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant
      differences were observed between ABO-compatible (ABOc) and ABOi grafts (P =
      .145). The biliary complication rate showed no significant difference (P = .195)
      between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not
      significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc
      graft combination seems to be a feasible option for expanding the donor pool
      without additional donor risks.

PMID- 28758335
TI  - Discordant rapid HIV tests: lessons from a low-resource community.
AB  - OBJECTIVES: HIV rapid antibody tests are widely used in Africa, but dual testing
      sometimes produces discordant results. It is not clear if discordant rapid HIV
      tests should always heighten suspicion by frontline health workers that early HIV
      infection is present. Some studies have reported that discordant rapid tests have
      value for identifying early HIV infection in high HIV prevalence populations. It
      is not known if rapid test performance influenced this conclusion, or if this
      observation will hold true for low HIV prevalence populations. We therefore
      explored the occurrence of discordant rapid HIV tests in a low-resource
      community. METHODS: A cross-sectional sample of HIV status-unaware adults with
      recent exposure to unsafe sex was assessed using a validated risk-based tool
      (University of North Carolina (UNC)-Malawi Risk Screening Score) for acute HIV
      infection. Participants received rapid testing with DetermineTM HIV 1/2 and Uni
      GoldTM HIV assays, plus plasma HIV-1 antigen testing with the COBAS(r)
      Ampliprep/COBAS(r) Taqman(r) HIV-1 assay, followed by western blot in those with
      detected HIV-1 antigen. RESULTS: Of 408 participants, 1.0% were confirmed to have
      established HIV infection. The discordance between rapid tests at initial
      screening was 2.45 and 2.94% when the two assays were used sequentially and
      simultaneously, respectively. Discordant rapid tests were strongly associated
      with risk scores > 2 [odds ratio (OR) 10.88; 95% confidence interval (CI) 2.35
      50.43], and with detected HIV-1 RNA (OR 26.06; 95% CI 3.91-173.60). CONCLUSIONS:
      When the sample occurrence of discordance between the first and second tests is
      below 5%, discordant rapid tests in an adult with sexual risk behaviour should
      trigger strong suspicion of early HIV infection in low HIV prevalence
      populations.

PMID- 28758337
TI  - Changes in the distribution of colonising and infecting Candida spp. isolates,
      antifungal drug consumption and susceptibility in a French intensive care unit: A
      10-year study.
AB  - Monitoring fungal ecology and resistance to antifungal agents within intensive
      care units (ICU) is essential for the management of invasive fungal infections.
      Therefore, a retrospective descriptive study was carried in the ICU of Nimes
      University Hospital, France, from 2007 to 2016. As the majority of invasive
      fungal infections in ICU are caused by Candida species, the study objectives were
      to describe Candida species distribution, to assess candidaemia incidence and to
      monitor the antifungal drug susceptibility of Candida isolates and the
      consumption of antifungal agents. Among the recorded invasive Candida infections
      (n=244), 43% were intra-abdominal and 22% bloodstream infections. Candida
      albicans was the most frequent species (55.8%), followed by Candida glabrata
      (14.1%), Candida tropicalis (10%), Candida parapsilosis (8%) and Candida krusei
      (5.3%). Candidaemia incidence was 4.49 per 1000 admissions. The mean consumption
      of antifungal agents was of 170.5 defined daily doses (DDD) for 1000 hospital
      days (HD) per year. Changes in antifungal drug consumption were observed, with an
      increased use of echinocandins (from 17.96 DDD/1000 HD in 2007 to 48.76 DDD/1000
      HD in 2016), and the total treatment cost tripled during the study period. No
      significant change in fungal ecology or in the emergence of resistant species was
      observed; indeed, only 1.1% of isolates presented an unusual resistance to
      antifungal agents.

PMID- 28758338
TI  - Dissecting Trichalcogenasumanenes: pi-Bowl to Planar, Invertible Curvature, and
      Chiral Polycycles.
AB  - The buckybowl trichalcogenasumanenes show cleavage of flanking benzene ring upon
      oxidation, which leads their dissection by fusing various amidine moieties onto
      peripheral region. By gradually increasing the ring size of amidine from five- to
      six- and seven-membered, the molecule engineering results in the [7-5-6]-, [7-6
      6]-, and [7-7-6]-fused polycycles. Three systems are distinct in the molecular
      geometries, packing motifs, and optoelectronic properties. The [7-5-6]-fused case
      adopts the flat backbone, displays strong emission with the fluorescence quantum
      yield up to 52.3 %, and undergoes a two-photon absorption process. The [7-6-6]
      fused one is of a curvature with molecular geometry inversion, forms a tight
      stack of curved pi-system, shows broad absorption extended to 700 nm, and
      exhibits the p-type semiconducting behavior with hole mobility of 4.4*10-3  cm2 
      V-1  s-1 . The [7-7-6]-fused one possesses the highly twisted skeleton to show
      stable chirality, and exhibits red emission in both solution and solid state. The
      surgery on trichalcogenasumanene is a promising approach to create polycycles
      with diverse functionalities.

PMID- 28758340
TI  - Nanocrystal-Dye Interactions: Studying the Feasibility of Co-Sensitization of
      Dyes with Semiconductor Nanocrystals.
AB  - One of the recent developments in enhancing the performance of quantum dot
      sensitized solar cells (QDSSCs) is to combine QDs with dyes in order to overcome
      the drawbacks of QDSSCs. However, implementation of this requires a detailed
      investigation of the interaction between QDs and dye. Here, we have studied the
      effect of size and surface ligands in the interaction of CdSe nanocrystals (NCs)
      with Ru N-719 dye. The interaction mechanism is investigated by steady-state and
      time-resolved photoluminescence spectroscopy, indicating the involvement of
      apparent static as well as dynamic quenching. Further analysis of dynamic
      quenching reveals the contribution of Forster resonance energy transfer and
      electron transfer from NCs to the dye. The Marcus model of electron transfer
      rationalizes the random trends of experimental electron transfer rates, which
      depend on the energetic offsets between the two species and the reorganizational
      energy. For understanding the kinetics of energy/charge transfer from CdSe NCs to
      Ru N-719 dye, a Poisson binding model has been proposed that assumes a Poisson
      distribution of dye molecules around CdSe NCs. The variation of quenching rate
      constants and PL quenching rate both follow the same trend, supporting the main
      contribution of kinetics in the interaction of CdSe NCs with the dye.

PMID- 28758339
TI  - Mitofusin 1 and optic atrophy 1 shift metabolism to mitochondrial respiration
      during aging.
AB  - Replicative and chronological lifespan are two different modes of cellular aging.
      Chronological lifespan is defined as the duration during which quiescent normal
      cells retain their capacity to re-enter the proliferative cycle. This study
      investigated whether changes in metabolism occur during aging of quiescent normal
      human fibroblasts (NHFs) and the mechanisms that regulate these changes.
      Bioenergetics measurements were taken in quiescent NHFs from younger (newborn, 3
      day, 5-month, and 1-year) and older (58-, 61-, 63-, 68-, and 70-year) healthy
      donors as well as NHFs from the same individual at different ages (29, 36, and 46
      years). Results show significant changes in cellular metabolism during aging of
      quiescent NHFs: Old NHFs exhibit a significant decrease in glycolytic flux and
      lactate levels, and increase in oxygen consumption rate (OCR) and ATP levels
      compared to young NHFs. Results from the Seahorse XF Cell Mito Stress Test show
      that old NHFs with a lower Bioenergetic Health Index (BHI) are more prone to
      oxidative stress compared to young NHFs with a higher BHI. The increase in OCR in
      old NHFs is associated with a shift in mitochondrial dynamics more toward fusion.
      Genetic knockdown of mitofusin 1 (MFN1) and optic atrophy 1 (OPA1) in old NHFs
      decreased OCR and shifted metabolism more toward glycolysis. Downregulation of
      MFN1 and OPA1 also suppressed the radiation-induced increase in doubling time of
      NHFs. In summary, results show that a metabolic shift from glycolysis in young to
      mitochondrial respiration in old NHFs occurs during chronological lifespan, and
      MFN1 and OPA1 regulate this process.

PMID- 28758341
TI  - Ten-year outcomes in a randomized phase II study of kidney transplant recipients
      administered belatacept 4-weekly or 8-weekly.
AB  - In the phase II IM103-100 study, kidney transplant recipients were first
      randomized to belatacept more-intensive-based (n = 74), belatacept less-intensive
      based (n = 71), or cyclosporine-based (n = 73) immunosuppression. At 3-6 months
      posttransplant, belatacept-treated patients were re-randomized to receive
      belatacept every 4 weeks (4-weekly, n = 62) or every 8 weeks (8-weekly, n = 60).
      Patients initially randomized to cyclosporine continued to receive cyclosporine
      based immunosuppression. Cumulative rates of biopsy-proven acute rejection (BPAR)
      from first randomization to year 10 were 22.8%, 37.0%, and 25.8% for belatacept
      more-intensive, belatacept less-intensive, and cyclosporine, respectively
      (belatacept more-intensive vs cyclosporine: hazard ratio [HR] = 0.95; 95%
      confidence interval [CI] 0.47-1.92; P = .89; belatacept less-intensive vs
      cyclosporine: HR = 1.61; 95% CI 0.85-3.05; P = .15). Cumulative BPAR rates from
      second randomization to year 10 for belatacept 4-weekly, belatacept 8-weekly, and
      cyclosporine were 11.1%, 21.9%, and 13.9%, respectively (belatacept 4-weekly vs
      cyclosporine: HR = 1.06, 95% CI 0.35-3.17, P = .92; belatacept 8-weekly vs
      cyclosporine: HR = 2.00, 95% CI 0.75-5.35, P = .17). Renal function trends were
      estimated using a repeated-measures model. Estimated mean GFR values at year 10
      for belatacept 4-weekly, belatacept 8-weekly, and cyclosporine were 67.0, 68.7,
      and 42.7 mL/min per 1.73 m2 , respectively (P<.001 for overall treatment effect).
      Although not statistically significant, rates of BPAR were 2-fold higher in
      patients administered belatacept every 8 weeks vs every 4 weeks.

PMID- 28758343
TI  - Strongly Coupled Molybdenum Carbide on Carbon Sheets as a Bifunctional
      Electrocatalyst for Overall Water Splitting.
AB  - High-performance and affordable electrocatalysts from earth-abundant elements are
      desirably pursued for water splitting involving hydrogen evolution reaction (HER)
      and oxygen evolution reaction (OER). Here, a bifunctional electrocatalyst of
      highly crystalline Mo2 C nanoparticles supported on carbon sheets (Mo2 C/CS) was
      designed toward overall water splitting. Owing to the highly active catalytic
      nature of Mo2 C nanoparticles, the high surface area of carbon sheets and
      efficient charge transfer in the strongly coupled composite, the designed
      catalysts show excellent bifunctional behavior with an onset potential of -60 mV
      for HER and an overpotential of 320 mV to achieve a current density of 10 mA cm-2
      for OER in 1 m KOH while maintaining robust stability. Moreover, the electrolysis
      cell using the catalyst only requires a low cell voltage of 1.73 V to achieve a
      current density of 10 mA cm-2 and maintains the activity for more than 100 h when
      employing the Mo2 C/CS catalyst as both anode and cathode electrodes. Such high
      performance makes Mo2 C/CS a promising electrocatalyst for practical hydrogen
      production from water splitting.

PMID- 28758342
TI  - Carrion fly-derived DNA metabarcoding is an effective tool for mammal surveys:
      Evidence from a known tropical mammal community.
AB  - Metabarcoding of vertebrate DNA derived from carrion flies has been proposed as a
      promising tool for biodiversity monitoring. To evaluate its efficacy, we
      conducted metabarcoding surveys of carrion flies on Barro Colorado Island (BCI),
      Panama, which has a well-known mammal community, and compared our results against
      diurnal transect counts and camera trapping. We collected 1,084 flies in 29
      sampling days, conducted metabarcoding with mammal-specific (16S) and vertebrate
      specific (12S) primers, and sequenced amplicons on Illumina MiSeq. For taxonomic
      assignment, we compared blast with the new program protax, and we found that
      protax improved species identifications. We detected 20 mammal, four bird, and
      one lizard species from carrion fly metabarcoding, all but one of which are known
      from BCI. Fly metabarcoding detected more mammal species than concurrent transect
      counts (29 sampling days, 13 species) and concurrent camera trapping (84 sampling
      days, 17 species), and detected 67% of the number of mammal species documented by
      8 years of transect counts and camera trapping combined, although fly
      metabarcoding missed several abundant species. This study demonstrates that
      carrion fly metabarcoding is a powerful tool for mammal biodiversity surveys and
      has the potential to detect a broader range of species than more commonly used
      methods.

PMID- 28758344
TI  - Characterizing the inpatient care of young adults experiencing early psychosis: A
      medical record review.
AB  - AIM: To characterize the inpatient care received by individuals experiencing
      early psychotic episodes in an inner city hospital. METHOD: Medical records of
      patients admitted between April 01, 2013, and March 31, 2015, to a psychiatric
      ward at an inner city hospital were retrospectively examined. Included in the
      study are patients who were 25 years of age or younger and were hospitalized for
      psychotic symptoms. Demographics and health service use were summarized using
      descriptive statistics. RESULTS: A total of 73 inpatients (mean age = 22; males
      =78%; Caucasian = 41%) met the study inclusion criteria with a combined total of
      102 care episodes and an average length of stay of 32.6 days. Monitoring of vital
      signs (VS) and mental status examinations (MSE) were performed in most care
      episodes although these were not performed regularly (daily VS checks-31%; MSE
      every nursing shift-18.6%). In 49% of the care episodes, patients were discharged
      on long-acting injectable antipsychotics. Even when indicated, not all care
      episodes had follow-up appointments (82.8%) in the community. The use of
      seclusion was higher in the wards (32%) than in the emergency department (21%),
      whereas the use of restraints was higher in the emergency department (16%) than
      in the wards (<1%). CONCLUSIONS: There is wide variation in the rate at which
      various clinical care processes are performed and in the provision of inpatient
      care to younger adults experiencing episodes of early psychosis. Consistent
      standards of care are needed to reduce variations and improve treatment outcomes
      and experiences.

PMID- 28758345
TI  - Does the computed tomographic appearance of the lung differ between young and old
      dogs?
AB  - In computed tomographic (CT) images of humans, decreased lung attenuation,
      bronchial dilation, and/or thickening, air trapping, cysts, and thickened
      interlobular septa have been associated with increasing age. To determine if
      there are differences in the CT appearance of the lungs of young and old dogs
      that could affect interpretation of diagnostic studies, pulmonary CT images of
      dogs with conditions unrelated to the thorax were reviewed retrospectively in a
      case-control study. Computed tomography studies of 42 young dogs (range 0.3-4.8
      years) and 47 old dogs (range 9-15.1 years) were jumbled and reviewed by an
      observer blinded to dog age. Computed tomography was performed under sedation in
      62 (70%) dogs and under general anesthesia in 27 (30%). Heterotopic bone was more
      prevalent (62% vs. 14%) in old dogs. Lung collapse was significantly associated
      with old age, greater body weight, and anesthesia. There were no significant
      differences in median lung attenuation or occurrence of ground glass pattern,
      cysts, bronchial thickening, bronchial dilation, or degree of tracheal
      calcification. No examples of reticular pattern, emphysema, pleural thickening,
      or septal thickening were observed in any dog. Despite previous studies
      describing age-related changes in the radiographic appearance of the lungs of old
      dogs, it appears that there are minimal observable differences in CT images. Old
      dogs are more likely to have visible foci of heterotopic bone and may be more
      prone to lung lobe collapse than young dogs, but neither of these differences
      should contribute to misdiagnosis of pulmonary disease.

PMID- 28758346
TI  - Direct detection and characterization of foot-and-mouth disease virus in East
      Africa using a field-ready real-time PCR platform.
AB  - Effective control and monitoring of foot-and-mouth disease (FMD) relies upon
      rapid and accurate disease confirmation. Currently, clinical samples are usually
      tested in reference laboratories using standardized assays recommended by The
      World Organisation for Animal Health (OIE). However, the requirements for prompt
      and serotype-specific diagnosis during FMD outbreaks, and the need to establish
      robust laboratory testing capacity in FMD-endemic countries have motivated the
      development of simple diagnostic platforms to support local decision-making.
      Using a portable thermocycler, the T-CORTM 8, this study describes the laboratory
      and field evaluation of a commercially available, lyophilized pan-serotype
      specific real-time RT-PCR (rRT-PCR) assay and a newly available FMD virus (FMDV)
      typing assay (East Africa-specific for serotypes: O, A, Southern African
      Territories [SAT] 1 and 2). Analytical sensitivity, diagnostic sensitivity and
      specificity of the pan-serotype-specific lyophilized assay were comparable to
      that of an OIE-recommended laboratory-based rRT-PCR (determined using a panel of
      57 FMDV-positive samples and six non-FMDV vesicular disease samples for
      differential diagnosis). The FMDV-typing assay was able to correctly identify the
      serotype of 33/36 FMDV-positive samples (no cross-reactivity between serotypes
      was evident). Furthermore, the assays were able to accurately detect and type
      FMDV RNA in multiple sample types, including epithelial tissue suspensions,
      serum, oesophageal-pharyngeal (OP) fluid and oral swabs, both with and without
      the use of nucleic acid extraction. When deployed in laboratory and field
      settings in Tanzania, Kenya and Ethiopia, both assays reliably detected and
      serotyped FMDV RNA in samples (n = 144) collected from pre-clinical, clinical and
      clinically recovered cattle. These data support the use of field-ready rRT-PCR
      platforms in endemic settings for simple, highly sensitive and rapid detection
      and/or characterization of FMDV.

PMID- 28758347
TI  - Prevalence, complete genome sequencing and phylogenetic analysis of porcine
      deltacoronavirus in South Korea, 2014-2016.
AB  - Porcine deltacoronavirus (PDCoV) is a newly emerged enterotropic swine
      coronavirus that causes enteritis and diarrhoea in piglets. Here, a nested
      reverse transcription (RT)-PCR approach for the detection of PDCoV was developed
      to identify and characterize aetiologic agent(s) associated with diarrhoeal
      diseases in piglets in South Korea. A PCR-based method was applied to investigate
      the presence of PDCoV in 683 diarrhoeic samples collected from 449 commercial pig
      farms in South Korea from January 2014 to December 2016. The molecular-based
      survey indicated a relatively high prevalence of PDCoV (19.03%) in South Korea.
      Among those, the monoinfection of PDCoV (9.66%) and co-infection of PDCoV (6.30%)
      with porcine epidemic diarrhoea (PEDV) were predominant in diarrhoeal samples.
      The full-length genomes or the complete spike genes of the most recent strains
      identified in 2016 (KNU16-07, KNU16-08 and KNU16-11) were sequenced and analysed
      to characterize PDCoV currently prevalent in South Korea. We found a single
      insertion-deletion signature and dozens of genetic changes in the spike (S) genes
      of the KNU16 isolates. Phylogenetic analysis based on the entire genome and spike
      protein sequences of these strains indicated that they are most closely related
      to other Korean isolates grouped with the US strains. However, Korean PDCoV
      strains formed different branches within the same cluster, implying continuous
      evolution in the field. Our data will advance the understanding of the molecular
      epidemiology and evolutionary characteristics of PDCoV circulating in South
      Korea.

PMID- 28758348
TI  - Preparative isolation of flavonoid glycosides from Sphaerophysa salsula using
      hydrophilic interaction solid-phase extraction coupled with two-dimensional
      preparative liquid chromatography.
AB  - An offline preparative two-dimensional reversed-phase liquid
      chromatography/hydrophilic interaction liquid chromatography coupled with
      hydrophilic interaction solid-phase extraction method was developed for the
      preparative isolation of flavonoid glycosides from a crude sample of Sphaerophysa
      salsula. First, the non-flavonoids were removed using an XAmide solid-phase
      extraction cartridge. Based on the separation results of three different
      chromatographic stationary phases, the first-dimensional preparation was
      performed on an XAqua C18 prep column, and 15 fractions were obtained from the
      5.2 g target sample. Then, three representative fractions were selected for
      additional purification on an XAmide preparative column to further isolate the
      flavonoid glycosides. In all, eight flavonoid glycosides were isolated in
      purities over 97%. The results demonstrated that the two-dimensional liquid
      chromatography method used in this study was effective for the preparative
      separation of flavonoid glycosides from Sphaerophysa salsula. Additionally, this
      method showed great potential for the separation of flavonoid glycosides from
      other plant materials.

PMID- 28758349
TI  - Appearance of US-like porcine epidemic diarrhoea virus (PEDV) strains before US
      outbreaks and genetic heterogeneity of PEDVs collected in Northern Vietnam during
      2012-2015.
AB  - Porcine epidemic diarrhoea virus (PEDV) is the aetiologic agent of porcine
      epidemic diarrhoea (PED), a highly contagious enteric disease that is threatening
      the swine industry globally. Since PED was first reported in Southern Vietnam in
      2009, the disease has spread throughout the country and caused substantial
      economic losses. To identify PEDVs responsible for the recent outbreaks, the full
      length spike (S) gene of 25 field PEDV strains collected from seven northern
      provinces of Vietnam was sequenced and analysed. The sequence analysis revealed
      that the S genes of Vietnamese PEDVs were heterogeneous and classified into four
      genotypes, namely North America and Asian non-S INDEL, Asian non-S INDEL, new S
      INDEL and classical S INDEL. This study reported the pre-existence of US-like
      PEDV strains in Vietnam. Thirteen Vietnamese variants had a truncated S protein
      that was 261 amino acids shorter than the normal protein. We also detected one
      novel variant with an 8-amino acid insertion located in the receptor-binding
      region for porcine aminopeptidase N. Compared to the commercial vaccine strains,
      the emerging Vietnamese strains were genetically distant and had various amino
      acid differences in epitope regions and N-glycosylation sites in the S protein.
      The development of novel vaccines based on the emerging Vietnamese strains may be
      contributive to the control of the current PED outbreaks.

PMID- 28758350
TI  - Nanostructured Three-Dimensional (3D) Assembly of 2D MoS2 and Graphene Directly
      Build From Acidic Graphite Oxide.
AB  - A 3D highly interconnected macroporous network of reduced GO having finely
      dispersed few-layered 2D MoS2 nanosheets was constructed through direct use of
      acidic graphite oxide (GO) for the first time. This facile and technologically
      scalable process can afford efficient hydrodesulfurization electrocatalysts as
      potential anode materials at lower cost, and can circumvent the poor thermal
      stability and recyclability of the material. The strategy provided here can be
      the basis to design and develop practical processes to address the ultimate goal
      of large-scale manufacturing of hybrids composed of 2D materials for various
      energy and catalysis applications.

PMID- 28758351
TI  - Structure and dimerization of the catalytic domain of the protein phosphatase
      Cdc14p, a key regulator of mitotic exit in Saccharomyces cerevisiae.
AB  - In the budding yeast Saccharomyces cerevisiae, the protein phosphatase Cdc14p
      orchestrates various events essential for mitotic exit. We have determined the X
      ray crystal structures at 1.85 A resolution of the catalytic domain of Cdc14p in
      both the apo state, and as a complex with S160-phosphorylated Swi6p peptide. Each
      asymmetric unit contains two Cdc14p chains arranged in an intimately associated
      homodimer, consistent with its oligomeric state in solution. The dimerization
      interface is located on the backside of the substrate-binding cleft. Structure
      based mutational analyses indicate that the dimerization of Cdc14p is required
      for normal growth of yeast cells.

PMID- 28758352
TI  - Fast digestive, leucine-rich, soluble milk proteins improve muscle protein
      anabolism, and mitochondrial function in undernourished old rats.
AB  - SCOPE: One strategy to manage malnutrition in older patients is to increase
      protein and energy intake. Here, we evaluate the influence of protein quality
      during refeeding on improvement in muscle protein and energy metabolism. METHODS
      AND RESULTS: Twenty-month-old male rats (n = 40) were fed 50% of their
      spontaneous intake for 12 weeks to induce malnutrition, then refed ad libitum
      with a standard diet enriched with casein or soluble milk proteins (22%) for 4
      weeks. A 13C-valine was infused to measure muscle protein synthesis and
      expression of MuRF1, and MAFbx was measured to evaluate muscle proteolysis. mTOR
      pathway activation and mitochondrial function were assessed in muscle.
      Malnutrition was associated with a decrease in body weight, fat mass, and lean
      mass, particularly muscle mass. Malnutrition decreased muscle mTOR pathway
      activation and protein FSR associated with increased MuRF1 mRNA levels, and
      decreased mitochondrial function. The refeeding period partially restored fat
      mass and lean mass. Unlike the casein diet, the soluble milk protein diet
      improved muscle protein metabolism and mitochondrial function in old malnourished
      rats. CONCLUSIONS: These results suggest that providing better-quality proteins
      during refeeding may improve efficacy of renutrition in malnourished older
      patients.

PMID- 28758354
TI  - An Examination of Correlates for Adolescent Engagement in Nonsuicidal Self
      Injury, Suicidal Self-Injury, and Substance Use.
AB  - Little research has examined potential risk factors for direct versus indirect
      self-injury among adolescents. To address this limitation, 541 clinically
      referred adolescents were assessed using the interRAI Child and Youth Mental
      Health Assessment. Logistic regression analyses revealed that older females who
      experienced heightened depressive symptoms and neighborhood violence were at
      increased risk for direct self-injury, specifically nonsuicidal and suicidal self
      injury. Additionally, adolescents who experienced higher levels of caregiver
      distress were at greater risk of suicidal self-injury. In contrast, older
      adolescents who experienced heightened aggressive behavior were at increased risk
      for one form of indirect self-injury, substance use. Findings suggest that
      nonsuicidal self-injury, suicidal self-injury, and substance use are associated
      with differential risk factors. Implications for targeted prevention strategies
      are discussed.

PMID- 28758353
TI  - Structural and SAXS analysis of Tle5-Tli5 complex reveals a novel inhibition
      mechanism of H2-T6SS in Pseudomonas aeruginosa.
AB  - Widely spread in Gram-negative bacteria, the type VI secretion system (T6SS)
      secretes many effector-immunity protein pairs to help the bacteria compete
      against other prokaryotic rivals, and infect their eukaryotic hosts. Tle5 and
      Tle5B are two phospholipase effector protein secreted by T6SS of Pseudomonas
      aeruginosa. They can facilitate the bacterial internalization process into human
      epithelial cells by interacting with Akt protein of the PI3K-Akt signal pathway.
      Tli5 and PA5086-5088 are cognate immunity proteins of Tle5 and Tle5B,
      respectively. They can interact with their cognate effector proteins to suppress
      their virulence. Here, we report the crystal structure of Tli5 at 2.8A resolution
      and successfully fit it into the Small angle X-ray scattering (SAXS) model of the
      complete Tle5-Tli5 complex. We identified two important motifs in Tli5 through
      sequence and structural analysis. One is a conserved loop-beta-hairpin motif that
      exists in the Tle5 immunity homologs, the other is a long and sharp alpha-alpha
      motif that directly interacts with Tle5 according to SAXS data. We also
      distinguished the structural features of Tle5 and Tle5B family immunity proteins.
      Together, our work provided insights into a novel inhibition mechanism that may
      enhance our understanding of phospholipase D family proteins.

PMID- 28758355
TI  - Role of the extracellular matrix in cancer-associated epithelial to mesenchymal
      transition phenomenon.
AB  - The epithelial to mesenchymal transition (EMT) program is a crucial component in
      the processes of morphogenesis and embryonic development. The transition of
      epithelial to mesenchymal phenotype is associated with numerous structural and
      functional changes, including loss of cell polarity and tight cell-cell
      junctions, the acquisition of invasive abilities, and the expression of
      mesenchymal proteins. The switch between the two phenotypes is involved in human
      pathology and is crucial for cancer progression. Extracellular matrices (ECMs)
      are multi-component networks that surround cells in tissues. These networks are
      obligatory for cell survival, growth, and differentiation as well as tissue
      organization. Indeed, the ECM suprastructure, in addition to its supportive role,
      can process and deliver a plethora of signals to cells, which ultimately regulate
      their behavior. Importantly, the ECM derived signals are critically involved in
      the process of EMT during tumorigenesis. This review discusses the multilayer
      interaction between the ECM and the EMT process, focusing on contributions of
      discrete mediators, a strategy that may identify novel potential target
      molecules. Developmental Dynamics 247:368-381, 2018. (c) 2017 Wiley Periodicals,
      Inc.

PMID- 28758356
TI  - End of life and people with intellectual disability.

PMID- 28758357
TI  - Thyroid Medication Use and Birth Defects in the National Birth Defects Prevention
      Study.
AB  - BACKGROUND: Thyroid disorders are common among reproductive-aged women, with
      hypothyroidism affecting 2 to 3% of pregnancies, and hyperthyroidism affecting an
      additional 0.1 to 1%. We examined associations between thyroid medications and
      individual birth defects using data from the National Birth Defects Prevention
      Study (NBDPS). METHODS: The NBDPS is a multisite, population-based, case-control
      study that included pregnancies with estimated delivery dates from 1997 to 2011.
      We analyzed self-reported thyroid medication use from mothers of 31,409 birth
      defect cases and 11,536 unaffected controls. Adjusted odds ratios (ORs) and 95%
      confidence intervals (CIs) were estimated using logistic regression for birth
      defects with five or more exposed cases, controlling for maternal age,
      race/ethnicity, and study center. Crude ORs and exact 95% CIs were estimated for
      defects with 3 to 4 exposed cases. RESULTS: Thyroid hormone was used by 738
      (2.3%) case and 237 (2.1%) control mothers, and was associated with anencephaly
      (OR = 1.68; 95% CI, 1.03-2.73), holoprosencephaly (OR = 2.48; 95% CI, 1.13-5.44),
      hydrocephaly (1.77; 95% CI, 1.07-2.95) and small intestinal atresia (OR = 1.81;
      95% CI, 1.04-3.15). Anti-thyroid medication was used by 34 (0.1%) case and 10
      (<0.1%) control mothers, and was associated with aortic valve stenosis (OR =
      6.91; 95% CI, 1.21-27.0). CONCLUSION: While new associations were identified, our
      findings are relatively consistent with previous NBDPS analyses. Our findings
      suggest thyroid medication use is not associated with most birth defects studied
      in the NBDPS, but may be associated with some specific birth defects. These
      results should not be interpreted to suggest that medications used to treat
      thyroid disease are teratogens, as the observed associations may reflect effects
      of the underlying thyroid disease. Birth Defects Research 109:1471-1481, 2017.(c)
      2017 Wiley Periodicals, Inc.

PMID- 28758358
TI  - Freeze-Drying as a Novel Biofabrication Method for Achieving a Controlled
      Microarchitecture within Large, Complex Natural Biomaterial Scaffolds.
AB  - The biofabrication of large natural biomaterial scaffolds into complex 3D shapes
      which have a controlled microarchitecture remains a major challenge. Freeze
      drying (or lyophilization) is a technique used to generate scaffolds in planar 3D
      geometries. Here we report the development of a new biofabrication process to
      form a collagen-based scaffold into a large, complex geometry which has a large
      height to width ratio, and a controlled porous microarchitecture. This
      biofabrication process is validated through the successful development of a heart
      valve shaped scaffold, fabricated from a collagen-glycosaminoglycan co-polymer.
      Notably, despite the significant challenges in using freeze-drying to create such
      a structure, the resultant scaffold has a uniform, homogenous pore architecture
      throughout. This is achieved through optimization of the freeze-drying mold and
      the freezing parameters. We believe this to be the first demonstration of using
      freeze-drying to create a large, complex scaffold geometry with a controlled,
      porous architecture for natural biomaterials. This study validates the potential
      of using freeze-drying for development of organ-specific scaffold geometries for
      tissue engineering applications, which up until now might not have been
      considered feasible.

PMID- 28758360
TI  - Essential Roles of Thyroid Hormone-Regulated Hyaluronan/CD44 Signaling in Adult
      Stem Cell Development During Xenopus laevis Intestinal Remodeling.
AB  - In the amphibian intestine during metamorphosis, thyroid hormone (TH) induces
      some larval epithelial cells to dedifferentiate into stem cells, which generate
      the adult epithelium analogous to the mammalian intestinal epithelium. We have
      previously shown that the canonical Wnt signaling pathway is involved in adult
      epithelial development in the Xenopus laevis intestine. To understand the
      function of this pathway more precisely, we here focused on CD44, a major Wnt
      target, which has been identified as a TH response gene in the X. laevis
      intestine. Our in situ hybridization analysis indicated that CD44 mRNA is
      detectable in adult epithelial primordia consisting of the adult stem/progenitor
      cells and is strongly expressed in the connective tissue (CT) cells surrounding
      them. Interestingly, when the expression of CD44 mRNA is the highest, hyaluronan
      (HA), a principle ligand of CD44, is newly synthesized and becomes most
      abundantly distributed in the CT just beneath the adult epithelial primordia that
      are actively proliferating. Thereafter, as the adult primordia differentiate into
      the simple columnar epithelium, the expression of CD44 mRNA is gradually
      downregulated. More importantly, using organ cultures of the X. laevis tadpole
      intestine in the presence of TH, we have experimentally shown that inhibition of
      HA synthesis by 4-methylumbelliferone suppresses development of not only the CT
      but also the epithelial stem cells, resulting in failure to generate the AE. Our
      findings strongly suggest that TH-upregulated HA/CD44 signaling plays an
      essential role in formation of the intestinal stem cell niche during vertebrate
      postembryonic development. Stem Cells 2017;35:2175-2183.

PMID- 28758359
TI  - Aggregation of SND1 in Stress Granules is Associated with the Microtubule
      Cytoskeleton During Heat Shock Stimulus.
AB  - Stress granules (SGs) are dynamic dense structures in the cytoplasm that form in
      response to a variety of environmental stress stimuli. Staphylococcal nuclease
      and Tudor domain containing 1 (SND1) is a type of RNA-binding protein and has
      been identified as a transcriptional co-activator. Our previous studies have
      shown that SND1 is a component of the stress granule, which forms under stress
      conditions. Here, we observed that SND1 granules were often surrounded by alpha
      tubulin-microtubules in 45 degrees C-treated HeLa cells at 15 min or colocalized
      with microtubules at 30 or 45 min. Furthermore, Nocodazole-mediated microtubule
      depolymerization could significantly affect the efficient recruitment of SND1
      proteins to the SGs during heat shock stress. In addition, the 45 degrees C heat
      shock mediated the enhancement of eIF2alpha phosphorylation, which was not
      affected by treatment with Nocodazole, an agent that disrupts the cytoskeleton.
      The intact microtubule cytoskeletal tracks are important for the efficient
      assembly of SND1 granules under heat shock stress and may facilitate SND1
      shuttling between cytoplasmic RNA foci. Anat Rec, 300:2192-2199, 2017. (c) 2017
      The Authors The Anatomical Record published by Wiley Periodicals, Inc. on behalf
      of American Association of Anatomists.

PMID- 28758361
TI  - IgY-binding peptide screened from a random peptide library as a ligand for IgY
      purification.
AB  - Chicken egg yolk immunoglobulin (IgY) is a functional substitute for mammalian
      IgG for antigen detection. Traditional IgY purification methods involve multi
      step procedures resulting in low purity and recovery of IgY. In this study, we
      developed a simple IgY purification system using IgY-specific peptides identified
      by T7 phage display technology. From disulfide-constrained random peptide
      libraries constructed on a T7 phage, we identified three specific binding clones
      (Y4-4, Y5-14, and Y5-55) through repeated biopanning. The synthetic peptides
      showed high binding specificity to IgY-Fc and moderate affinity for IgY-Fc (Kd :
      Y4-4 = 7.3 +/- 0.2 MUM and Y5-55 = 4.4 +/- 0.1 MUM) by surface plasmon resonance
      analysis. To evaluate the ability to purify IgY, we performed immunoprecipitation
      and affinity high-performance liquid chromatography using IgY-binding peptides;
      the result indicated that these peptides can be used as affinity ligands for IgY
      purification. We then used a peptide-conjugated column to purify IgY from egg
      yolks pre-treated using an optimized delipidation technique. Here, we report the
      construction of a cost-effective, one-step IgY purification system, with high
      purity and recovery. (c) 2017 The Authors. Journal of Peptide Science published
      by European Peptide Society and John Wiley & Sons Ltd.

PMID- 28758362
TI  - Metabolomic Determinants of Metabolic Risk in Mexican Adolescents.
AB  - OBJECTIVE: The goal of this study was to identify metabolites associated with
      metabolic risk, separately by sex, in Mexican adolescents. METHODS: Untargeted
      metabolomic profiling was carried out on fasting serum of 238 youth aged 8 to 14
      years, and metabolites associated with a metabolic syndrome risk z-score (MetRisk
      z-score) were identified separately for boys and girls, using the simulation and
      extrapolation algorithm. Associations of each metabolite with MetRisk z-score
      were examined using linear regression models that accounted for maternal
      education, child's age, and pubertal status. RESULTS: Of the 938 features
      identified in metabolomics analysis, 7 named compounds (of 27 identified
      metabolites) were associated with MetRisk z-score in girls, and 3 named compounds
      (of 14 identified) were associated with MetRisk z-score in boys. In girls,
      diacylglycerol (DG) 16:0/16:0, 1,3-dielaidin, myo-inositol, and urate
      corresponded with higher MetRisk z-score, whereas N-acetylglycine, thymine, and
      dodecenedioic acid were associated with lower MetRisk z-score. For example, each
      z-score increment in DG 16:0/16:0 corresponded with 0.60 (95% CI: 0.47-0.74)
      units higher MetRisk z-score. In boys, positive associations of DG 16:0/16:0,
      tyrosine, and 5'-methylthioadenosine with MetRisk z-score were found.
      CONCLUSIONS: Metabolites on lipid, amino acid, and carbohydrate metabolism
      pathways are associated with metabolic risk in girls. Compounds on lipid and DNA
      pathways correspond with metabolic risk in boys.

PMID- 28758363
TI  - Validation of an LC-MS/MS method for analysis of anti-diabetic drugs in botanical
      dietary supplements labeled for blood sugar management.
AB  - We developed and validated a liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method to detect and quantitate 14 anti-diabetic, 2 anti-obesity, and 3
      cholesterol-lowering drugs in botanical dietary supplements marketed for blood
      sugar management. Many botanical dietary supplements which carry label statements
      related to blood sugar management are available over the Internet. Potential
      adulteration of such dietary supplements with anti-diabetic and other
      prescription drugs, some of which have been removed from the market due to
      adverse events, is of concern. No significant matrix effects were observed and
      mean recoveries of all 19 analytes from a single product matrix were 88 to 113%
      at spiking concentrations from 500 to 2000 MUg/g. Mean recoveries of metformin,
      phenformin, and sibutramine from matrices prepared from multiple product
      composites ranged from 93 to 115% at a spiking concentration of 100 MUg/g. The
      relative standard deviations (RSD) (%) of intra-day analyses ranged from 0.2 to
      13 for all recovery studies. Eighty dietary supplements obtained in the USA and
      carrying label statements related to blood sugar management were analyzed using
      this method and none were found to be adulterated with the above 19 drugs. Two
      products obtained outside of the USA and known to be adulterated were also
      analyzed by this method and found to contain phenformin, glibenclamide, and
      sibutramine. This method provided satisfactory selectivity, linearity, accuracy,
      precision, and sensitivity for rapid determination of 19 drugs and has broad
      applicability for the analysis of dietary supplements for possible adulteration
      with these compounds.

PMID- 28758364
TI  - The outstanding questions in transplantation: It's about time....

PMID- 28758365
TI  - Evaluation of the safety of iron dextran with parenteral nutrition in the
      paediatric inpatient setting.
AB  - AIM: Practitioners often avoid administering iron dextran in parenteral nutrition
      (PN) for hospitalised children because of the concern for anaphylaxis. The
      primary aim of the present study was to determine the risk of anaphylaxis
      associated with exposure to PN containing iron dextran in the inpatient setting.
      METHODS: Charts were reviewed for all children admitted to The Children's
      Hospital of Philadelphia from January 1, 2011 to December 30, 2013 who received
      PN containing low molecular weight (LMW) iron dextran. Subject characteristics,
      primary diagnoses and PN orders were evaluated. The pharmacy adverse events
      database was queried for adverse drug reactions. RESULTS: Over three years, 89
      subjects received PN containing a maintenance dose of LMW iron dextran with a
      total of 2774 days of exposure. Subjects ranged from two months to 21 years of
      age and received between 1 and 196 days of PN containing iron dextran. The mean
      dose of iron dextran in children decreased as the weight category increased from
      <5 kg (0.21 +/- 0.05 mg/kg/day) to >=40 kg (1.9 +/- 0.5 mg/day; P-value for trend
      <0.005). No anaphylactic reactions occurred in any subjects. CONCLUSIONS: PN
      containing a maintenance dose of LMW iron dextran can be safely administered to
      hospitalised children, and further studies are need to evaluate the potential to
      prevent iron deficiency anaemia and the need for additional IV iron infusions.

PMID- 28758366
TI  - Pyrrolysine Amber Stop-Codon Suppression: Development and Applications.
AB  - The pyrrolysine tRNA synthetase-tRNA pair is probably one of the most promiscuous
      tRNA-synthetase pairs found in nature, capable of genetically encoding a plethora
      of noncanonical amino acids through stop codon reassignment. Proteins containing
      reactive handles, post-translational modification mimics or both can be produced
      in practical quantities, allowing inter alia the probing of biological pathways,
      generating antibody-drug conjugates and enhancing protein function. This
      Minireview summarises the development of pyrrolysine amber stop-codon
      suppression, presents some of the considerations required to utilise this
      technique to its greatest potential, and showcases the creative ways in which
      this technique has led to a better understanding of biological systems.

PMID- 28758367
TI  - HoBi-like is the most prevalent ruminant pestivirus in Northeastern Brazil.
AB  - The ruminant pestiviral species BVDV-1, BVDV-2 and BDV, along with the putative
      species HoBi-like, may cause substantial economic losses in cattle, sheep and
      goats. Brazil's large size, variable biomes and wide range of ruminant animal
      production within different geographic regions suggest that the presence and
      prevalence of ruminant pestivirus may differ by regions within Brazil. This study
      investigated the genetic diversity of ruminant pestiviruses and determined the
      frequency of active infections within two states of the Northeast Region of
      Brazil, Maranhao and Rio Grande do Norte. Serum samples from 16,621 cattle and
      2,672 small ruminants from 569 different herds residing in this region were
      tested by RT-PCR followed by DNA sequencing. Seventeen positive cattle were
      detected (0.1%) from fifteen different herds (2.64%). All isolates were
      classified as HoBi-like pestiviruses based on phylogenetic analysis. All small
      ruminant samples tested negative. The findings presented herein suggest that the
      Northeast Region of Brazil has a uniquely high prevalence of HoBi-like viruses.
      The increasing reports of HoBi-like viruses detected in cattle in the field
      suggest that natural infection with these viruses may be more widespread than
      previously thought. The identification of HoBi-like viruses as the most prevalent
      type of ruminant pestivirus circulating in the Northeast Region of Brazil
      indicates the need for both continued monitoring and determination of the extent
      of economic losses associated with HoBi-like virus infections. In addition, it
      must be taken into account in the choice of diagnostic tests and in vaccine
      formulations.

PMID- 28758368
TI  - Composition and structure of porcine digital flexor tendon-bone insertion
      tissues.
AB  - Tendon-bone insertion is a functionally graded tissue, transitioning from 200 MPa
      tensile modulus at the tendon end to 20 GPa tensile modulus at the bone, across
      just a few hundred micrometers. In this study, we examine the porcine digital
      flexor tendon insertion tissue to provide a quantitative description of its
      collagen orientation and mineral concentration by using Fast Fourier Transform
      (FFT) based image analysis and mass spectrometry, respectively. Histological
      results revealed uniformity in global collagen orientation at all depths,
      indicative of mechanical anisotropy, although at mid-depth, the highest fiber
      density, least amount of dispersion, and least cellular circularity were evident.
      Collagen orientation distribution obtained through 2D FFT of histological imaging
      data from fluorescent microscopy agreed with past measurements based on polarized
      light microscopy. Results revealed global fiber orientation across the tendon
      bone insertion to be preserved along direction of physiologic tension. Gradation
      in the fiber distribution orientation index across the insertion was reflective
      of a decrease in anisotropy from the tendon to the bone. We provided elemental
      maps across the fibrocartilage for its organic and inorganic constituents through
      time-of-flight secondary ion mass spectrometry (TOF-SIMS). The apatite intensity
      distribution from the tendon to bone was shown to follow a linear trend,
      supporting past results based on Raman microprobe analysis. The merit of this
      study lies in the image-based simplified approach to fiber distribution
      quantification and in the high spatial resolution of the compositional analysis.
      In conjunction with the mechanical properties of the insertion tissue, fiber, and
      mineral distribution results for the insertion from this may potentially be
      incorporated into the development of a structural constitutive approach toward
      computational modeling. Characterizing the properties of the native insertion
      tissue would provide the microstructural basis for developing biomimetic
      scaffolds to recreate the graded morphology of a fibrocartilaginous insertion.
      (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3050-3058,
      2017.

PMID- 28758369
TI  - Early Life Factors, Obesity Risk, and the Metabolome of Young Adults.
AB  - OBJECTIVE: Noncommunicable diseases such as obesity have become a serious global
      public health epidemic. This study aimed to examine whether there was an
      association between early life factors (with a special focus on breastfeeding)
      BMI, waist circumference, and the metabolome in offspring at 20 years. METHODS:
      Data from the Western Australian Pregnancy Cohort (Raine) Study were analyzed
      using 1,024 plasma samples from the 20-year follow-up. A liquid chromatography,
      tandem mass spectrometry metabolomics approach was used to measure metabolites.
      Multiple linear regression models were performed and adjusted for relevant
      confounders. Inverse probability weighting was used to adjust the 20-year data
      for differences in socioeconomic variables between participants and
      nonparticipants since the commencement of the study. RESULTS: An inverse
      association between breastfeeding and BMI or waist circumference at 20 years was
      lost after adjusting for parental prepregnancy BMI and maternal smoking during
      pregnancy. There was no significant effect of breastfeeding on metabolite
      concentrations at 20 years. CONCLUSIONS: Although other studies have shown
      associations between breastfeeding, obesity, and metabolite concentrations at
      younger ages, this was not evident in our study in young adults. We found no
      association of metabolites previously associated with waist circumference at 20
      years and breastfeeding in early life.

PMID- 28758371
TI  - Magnitude of workplace violence in emergency department: another brick in the
      wall.

PMID- 28758370
TI  - Validity of the Remote Food Photography Method Against Doubly Labeled Water Among
      Minority Preschoolers.
AB  - OBJECTIVE: The aim of this study was to determine the validity of energy intake
      (EI) estimations made using the remote food photography method (RFPM) compared to
      the doubly labeled water (DLW) method in minority preschool children in a free
      living environment. METHODS: Seven days of food intake and spot urine samples
      excluding first void collections for DLW analysis were obtained on thirty-nine 3-
      to 5-year-old Hispanic and African American children. Using an iPhone, caregivers
      captured before and after pictures of each child's intake, pictures were
      wirelessly transmitted to trained raters who estimated portion size using
      existing visual estimation procedures, and energy and macronutrients were
      calculated. Paired t tests, mean differences, and Bland-Altman limits of
      agreement were performed. RESULTS: The mean EI was 1,191 +/- 256 kcal/d using the
      RFPM and 1,412 +/- 220 kcal/d using the DLW method, resulting in a mean
      underestimate of 222 kcal/d (-15.6%; P < 0.0001) that was consistent regardless
      of intake. The RFPM underestimated EI by -28.5% in 34 children and overestimated
      EI by 15.6% in 5 children. CONCLUSIONS: The RFPM underestimated total EI when
      compared to the DLW method among preschoolers. Further refinement of the RFPM is
      needed for assessing the EI of young children.

PMID- 28758372
TI  - Metabolomic Profiling of Long-Term Weight Change: Role of Oxidative Stress and
      Urate Levels in Weight Gain.
AB  - OBJECTIVE: To investigate the association between long-term weight change and
      blood metabolites. METHODS: Change in BMI over 8.6 +/- 3.79 years was assessed in
      3,176 females from the TwinsUK cohort (age range: 18.3-79.6, baseline BMI: 25.11
      +/- 4.35) measured for 280 metabolites at follow-up. Statistically significant
      metabolites (adjusting for covariates) were included in a multivariable least
      absolute shrinkage and selection operator (LASSO) model. Findings were replicated
      in the Cooperative Health Research in the Region of Augsburg (KORA) study (n =
      1,760; age range: 25-70, baseline BMI: 27.72 +/- 4.53). The study examined
      whether the metabolites identified could prospectively predict weight change in
      KORA and in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) study (n =
      471; age range: 55-74, baseline BMI: 27.24 +/- 5.37). RESULTS: Thirty metabolites
      were significantly associated with change in BMI per year in TwinsUK using
      Bonferroni correction. Four were independently associated with weight change in
      the multivariable LASSO model and replicated in KORA: namely, urate (meta
      analysis beta [95% CI] = 0.05 [0.040 to 0.063]; P = 1.37 * 10-19 ), gamma
      glutamyl valine (beta [95% CI] = 0.06 [0.046 to 0.070]; P = 1.23 * 10-20 ),
      butyrylcarnitine (beta [95% CI] = 0.04 [0.028 to 0.051]; P = 6.72 * 10-12 ), and
      3-phenylpropionate (beta [95% CI] = -0.03 [-0.041 to -0.019]; P = 9.8 * 10-8 ),
      all involved in oxidative stress. Higher levels of urate at baseline were
      associated with weight gain in KORA and PLCO. CONCLUSIONS: Metabolites linked to
      higher oxidative stress are associated with increased long-term weight gain.

PMID- 28758373
TI  - Fetal Cerebral Ventricular Dilatation: Etiopathogenic Study of 130 Observations.
AB  - BACKGROUND: Fetal cerebral ventricular dilatation (CVD) is a common abnormal
      prenatal finding that often predicts a poor prognosis. The etiology involves both
      genetic and nongenetic factors with diverse pathogenic mechanisms. We describe
      the neuropathological features of CVD in a large cohort of fetuses. The goals are
      to determine the physiopathological mechanisms and etiologies. METHODS: We
      retrospectively analyzed a series of 130 fetuses examined at the Necker
      University Hospital following termination of pregnancy between January 2000 and
      December 2014. Chiari II and Dandy-Walker malformations were excluded from our
      study population. Karyotype and/or array comparative genomic hybridization were
      performed in all cases. Targeted Sanger sequencing or next generation sequencing
      were carried out in 34 and 5 cases, respectively. RESULTS: We distinguished four
      groups of pathological entities: (1) midbrain/hindbrain patterning defects (54
      cases, 42%), mainly related to aqueduct of Sylvius anomalies (atresia or
      stenosis); (2) cerebral cytoarchitectonic disorders (16 cases, 12%), essentially
      resulting from arachnoidal neuroglial ectopia; (3) hemorrhagic and perfusion
      failure (42 cases, 32%); and (4) nonspecific CVD (18 cases, 14%), without
      apparent obstruction, cortical malformation, or clastic injury. Although the
      pathogenic mechanisms of CVD were identified in 86% of cases, the causes, both
      acquired and genetic, were recognized in 21% of cases only. CONCLUSION: The
      neuropathological analysis is a powerful tool in the diagnosis of the fetal CVD
      pathogenic mechanisms and to identify homogeneous groups. The paucity of
      molecular diagnosis, notably in the major groups of midbrain/hindbrain patterning
      defects and hemorrhagic and perfusion failure, highlights the needs of future
      research to improve our current knowledge on CVD causes. Birth Defects Research
      109:1586-1595, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28758374
TI  - Circular dichroism spectroscopy: Enhancing a traditional undergraduate
      biochemistry laboratory experience.
AB  - The undergraduate biochemistry laboratory curriculum is designed to provide
      students with experience in protein isolation and purification protocols as well
      as various data analysis techniques, which enhance the biochemistry lecture
      course and give students a broad range of tools upon which to build in graduate
      level laboratories or once they begin their careers. One of the most common
      biochemistry protein purification experiments is the isolation and
      characterization of cytochrome c. Students across the country purify cytochrome
      c, lysozyme, or some other well-known protein to learn these common purification
      techniques. What this series of experiments lacks is the use of sophisticated
      instrumentation that is rarely available to undergraduate students. To give
      students a broader background in biochemical spectroscopy techniques, a new
      circular dichroism (CD) laboratory experiment was introduced into the
      biochemistry laboratory curriculum. This CD experiment provides students with a
      means of conceptualizing the secondary structure of their purified protein, and
      assessments indicate that students' understanding of the technique increased
      significantly. Students conducted this experiment with ease and in a short time
      frame, so this laboratory is conducive to merging with other data analysis
      techniques within a single laboratory period. (c) 2017 by The International Union
      of Biochemistry and Molecular Biology, 45(6):515-520, 2017.

PMID- 28758375
TI  - All bereaved parents are entitled to good care after stillbirth: a mixed-methods
      multicentre study (INSIGHT).
AB  - OBJECTIVE: To understand challenges in care after stillbirth and provide tailored
      solutions. DESIGN: Multi-centre case study. SETTING: Three maternity hospitals.
      POPULATION: Parents with a stillborn baby, maternity staff. METHODS: Thematic
      analysis of parent interviews and staff focus groups and service provision
      investigation. OUTCOMES: 1 Themes; 2 Triangulation matrix; 3 Recommendations.
      RESULTS: Twenty-one women, 14 partners, and 22 staff participated. Service
      Provision: Care for parents after stillbirth varies excessively; there are
      misconceptions; post-mortem does not delay follow-up. PRESENTATION: Women 'do not
      feel right' before stillbirth; their management is haphazard and should be
      standardised. DIAGNOSIS: Stillbirth is an emergency for parents but not always
      for staff; communication can seem cold; well-designed bereavement space is
      critical. Birth: Staff shift priorities to mother and future, but for parents
      their baby is still a baby; parents are not comfortable with staff recommending
      vaginal birth as the norm; there are several reasons why parents ask for a
      caesarean; better care involves clear communication, normal behaviour, and
      discussion of coping strategies. Post-mortem: Parents are influenced by
      discussions with staff. Staff should 'sow seeds', clarify its respectful nature,
      delineate its purpose, and explain the timescale. FOLLOW-UP: It is not
      standardised; parents wish to see their multi-professional team. CONCLUSIONS:
      There is unacceptable variation in care after stillbirth, and insensitive
      interactions between staff and bereaved parents. Understanding parents' needs,
      including why they ask for caesarean birth, will facilitate joint decision
      making. Every bereaved parent is entitled to good, respectful care. TWEETABLE
      ABSTRACT: Care too varied & interactions often insensitive after stillbirth;
      national pathway & training urgently needed PLAIN LANGUAGE SUMMARY: Why and how
      was the study carried out? Previous studies have shown that improving care after
      stillbirth is important for families. We investigated the opinions of bereaved
      parents and maternity staff to find ways to improve care. At three hospitals in
      2013, all women who experienced a stillbirth were invited to an interview along
      with their partners. Thirty-five parents of 21 babies agreed to participate.
      Twenty-two obstetricians and midwives took part in focus group discussions. What
      were the main findings? Care was often not as good as it should and could be.
      Communication with parents was not always as sensitive as they would have liked
      because staff did not have appropriate training. Some women reported they did not
      'feel right' before going to hospital. Once they arrived, there was no standard
      approach to how care was given. Sometimes there were long delays before the death
      of the baby was confirmed and action was taken. After it had been confirmed that
      the baby had died, staff focussed on the mothers' needs, but the parents'
      priorities were still with their baby. There were several reasons why parents
      asked for a caesarean birth that staff had not considered. Staff influenced
      parents' decisions about post-mortem examinations. Parents found it helpful when
      staff explained the respectful nature and purpose of the examination. After
      discharge from hospital, there was no consistent plan for how follow-up care
      would be given. Parents would have liked more information about their next
      hospital appointment. What are the limitations of the work? The parents
      interviewed depended on their memories of the details of the care, which happened
      some time ago. In staff group discussions, junior doctors may not have spoken
      openly because there were senior doctors present. Further research is necessary
      to understand and improve care globally. What is the implication for parents?
      Every bereaved parent is entitled to the best possible care after stillbirth, but
      some do not get good care. Parents and staff made suggestions that can help to
      develop processes for how care is given after stillbirth. These suggestions can
      also inform staff training, so that every single parent is treated respectfully
      and participates in decision making.

PMID- 28758377
TI  - Could fertility-sparing surgery be considered for women with early stage ovarian
      clear cell carcinoma?
AB  - OBJECTIVE: The aim of the present retrospective population-based study was to
      investigate the oncologic impact of uterine and ovarian preservation (OP) in
      premenopausal women with stage IA or IC ovarian clear cell carcinoma (OCCC).
      METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End
      Results (SEER) database was accessed and a cohort of surgically-staged
      premenopausal women (age <50 years) diagnosed with unilateral stage IA or IC OCCC
      was drawn. Based on site-specific surgery codes, women who did not undergo
      hysterectomy and/or bilateral salpingo-oophorectomy (BSO) were identified.
      Overall survival (OS) and cancer-specific survival (CSS) rates were calculated
      following generation of Kaplan-Meier curves; comparisons were made with the log
      rank test. Multivariate Cox analysis was performed to control for possible
      confounders. RESULTS: A total of 741 premenopausal women who met the inclusion
      criteria were identified. Based on available information, rate of uterine
      preservation was 14.5% (96/663) while the rate of OP was 28.1% (71/253). Five
      year CSS rates were 90.8% for women who did not undergo hysterectomy compared
      with 87.7% for those who did (p=0.290). Similarly, 5-year CSS rates in the OP and
      BSO groups were 92.6% and 85%, respectively (p=0.060). After controlling for
      disease sub-stage (IA vs. IC), uterine or OP was not associated with a worse
      overall or cancer-specific mortality. CONCLUSION: In the present cohort, uterine
      and OP did not have a negative impact on oncologic outcomes. Selection criteria
      for fertility-sparing surgery (FSS) could be expanded to include women with stage
      IA OCCC.

PMID- 28758378
TI  - Fear of cancer recurrence and its predictors among cervical cancer survivors.
AB  - OBJECTIVE: To identify the characteristics of fear of cancer recurrence (FCR) in
      cervical cancer survivors (CCSs) and investigate the relationship of FCR with
      demographic and medical characteristics, level of quality of life (QOL), and
      psychological distress. We also aimed to determine the predictors of FCR.
      METHODS: The short version of the Fear of Progression Questionnaire (FoP-Q-SF),
      the Hospital Anxiety and Depression Scale (HADS), and the Functional Assessment
      of Cancer Therapy-Cervical (FACT-Cx) questionnaire were administered to 699 CCSs
      who had complete treatment at Songklanagarind Hospital between 2006 and 2016.
      Analysis was performed to determine potential predictors associated with FCR.
      RESULTS: Among the 12 items of the FoP-Q-SF, the 3 greatest fears were 1)
      worrying about what would happen to their family; 2) being afraid of pain; and 3)
      fear of disease progression. The prevalences of anxiety and depression disorder
      were 20.46% and 9.44%, respectively. CCSs who had FCR at the 5th quintile were
      more likely to have medical co-morbidities, low FACT-Cx scores in all domains and
      a high HADS scores (anxiety and depression disorder). Multivariate analysis
      showed that only anxiety disorder (odds ratio [OR]=4.99; p<0.001) and low FACT-Cx
      score (total) (OR=6.14; p<0.001) were identified as independent predictors for
      FCR at the 5th quintile. CONCLUSION: FCR is an important problem in cervical
      cancer which should be addressed during post-treatment care. Only anxiety
      disorder and low QOL were independently associated with high FCR.

PMID- 28758379
TI  - External validation of chemotherapy response score system for histopathological
      assessment of tumor regression after neoadjuvant chemotherapy in tubo-ovarian
      high-grade serous carcinoma.
AB  - OBJECTIVE: The chemotherapy response score (CRS) system based on
      histopathological examination has been recently proposed for tubo-ovarian high
      grade serous carcinoma (HGSC) to assess response to neoadjuvant chemotherapy
      (NAC). This study was aimed at validating the CRS system in an external cohort of
      tubo-ovarian HGSC patients. METHODS: This study included 110 tubo-ovarian HGSC
      patients who underwent NAC followed by interval debulking surgery. The 3-tiered
      CRS of the omental and adnexal tissue sections was determined by 3 independent
      pathologists. Differences in patient outcomes according to CRS were analyzed.
      RESULTS: The CRS system was highly reproducible among the 3 pathologists. Fleiss'
      kappa value and Kendall's coefficient of concordance for the omental CRS were
      0.656 and 0.669, respectively. The omental CRS significantly predicted
      progression-free survival (PFS). The median PFS of patients whose tumors
      exhibited the omental CRS 1-2 (15 months) was significantly shorter than that of
      patients with an omental CRS of 3 (19 months; p=0.016). In addition, after
      adjusting for age, stage, and debulking status, the omental CRS was an
      independent prognostic factor for PFS of tubo-ovarian HGSC patients who were
      treated with NAC (adjusted hazard ratio [HR]=1.74; 95% confidence interval
      [CI]=1.05-2.87). CONCLUSION: The CRS system for assessing NAC response was a
      reproducible prognostic tool in our cohort. The application of the CRS system
      after NAC can improve survival estimation in HGSC patients.

PMID- 28758380
TI  - Highlights from the Gynecologic Oncology Track at the 2017 Annual Meeting of the
      American Society of Clinical Oncology.

PMID- 28758381
TI  - The Impact of Allergic Rhinitis on Symptom Improvement in Pediatric Patients
      After Adenotonsillectomy.
AB  - OBJECTIVES: It is well known that allergic rhinitis (AR) has positive association
      with adenotonsillectomy. However, the impact of AR on symptom improvement after
      adenotonsillectomy is not well documented. Hence, we aimed to evaluate the effect
      of AR on the symptom improvement after adenotonsillectomy between AR and
      nonallergic patients. METHODS: A retrospective analysis was performed on 250
      pediatric patients younger than 10 years old who received adenotonsillectomy from
      June 2009 to June 2014 in a tertiary referral hospital. All patients underwent
      skin prick test or multiple allergen simultaneous test (MAST) before surgery and
      classified into AR group and control group. Obstructive and rhinitis symptoms
      including snoring, mouth breathing, nasal obstruction, rhinorrhea, itching, and
      sneezing were evaluated before and 1 year after surgery using questionnaire and
      telephone survey. RESULTS: AR group was 131 and control group was 119, showing
      higher prevalence (52.4%) of AR among adenotonsillectomized patients. Both groups
      showed dramatic improvement of symptoms such as snoring and mouth breathing after
      surgery (all P<0.05). However, AR group showed significantly less improvement
      than control group in snoring, mouth breathing, nasal obstruction, and rhinorrhea
      (all P<0.05). Multivariate analysis showed that preoperative mouth breathing and
      snoring were dependent on tonsil grade and postoperative symptoms were mainly
      dependent on presence of AR. Nasal obstruction was dependent on tonsil grade and
      presence of AR preoperatively and presence of AR postoperatively. These suggest
      the importance of AR as a risk factor for mouth breathing, snoring, and nasal
      obstruction. CONCLUSION: AR has positive association with adenotonsillectomy and
      not only allergic symptoms but also obstructive symptoms such as snoring and
      mouth breathing improved less in AR group than control group. Hence, patients
      with AR should be monitored for long-term basis and more carefully after
      adenotonsillectomy.

PMID- 28758383
TI  - Single Organic Droplet Collision Voltammogram via Electron Transfer Coupled Ion
      Transfer.
AB  - Single-emulsion toluene oil droplets (femtoliter) containing a hydrophobic redox
      probe that are dispersed in water stochastically collide with an
      ultramicroelectrode (UME). The fast-scan cyclic voltammetry (FSCV) or Fourier
      transformed sinusoidal voltammetry (FTSV) is applied: the UME was scanned with a
      fast, repetitive triangular, or sinusoidal potential, and its current in
      time/frequency domains were monitored. The electron transfer at the UME/oil
      interface is coupled with ion transfer at the oil/water interface. Thus, the
      obtained transient voltammograms of a myriad of ions were used to estimate
      thermodynamics of ion transfer at the toluene/water interface. Additionally, the
      single-droplet voltammogram combined with finite element simulations reveal the
      droplet's size and shape distributions. Four collision mechanisms with new
      physical insights were also uncovered via comprehensive analysis of phase angle
      in the frequency domain, time domain FSCVs, and finite element simulations.

PMID- 28758384
TI  - Nanoelectronic Discrimination of Nonmalignant and Malignant Cells Using Nanotube
      Field-Effect Transistors.
AB  - Detection of malignant cells in tissue is a difficult hurdle in medical
      diagnostics and screening. Carbon nanotubes are extremely sensitive to their
      local environments, and nanotube-based field-effect transistors (NTFETs) provide
      a plethora of information regarding the mechanism of interaction with target
      analytes. Herein, we use a series of functionalized metal nanoparticle-decorated
      NTFET devices forming an array with multiple nonselective sensor units as the
      electronic "tongue", sensing all five basic tastes. By extraction of selected
      NTFET characteristics and using linear discriminant analysis, we have
      successfully detected and discriminated between malignant and nonmalignant
      tissues and cells. We also studied the sensing mechanism and what NTFET
      characteristics are responsible for the variation of response between cell types,
      allowing for the design of future studies such as detection of malignant cells in
      a biopsy or the effects of malignant cells on healthy tissue.

PMID- 28758385
TI  - Mg Isotope Fractionation during Uptake by a Rock-Inhabiting, Model Microcolonial
      Fungus Knufia petricola at Acidic and Neutral pH.
AB  - The model rock-inhabiting microcolonial fungus Knufia petricola fractionates
      stable Mg isotopes in a time- and pH-dependent manner. During growth, the
      increase of 26Mg/24Mg in the fungal cells relative to the growth media amounted
      to 0.65 +/- 0.140/00 at pH 6 and 1.11 +/- 0.350/00 at pH 3. We suggest a constant
      equilibrium fractionation factor during incorporation of Mg into ribosomes and
      ATP as a cause of enrichment of 26Mg in the cells. We suggest too that the proton
      gradient across the cell wall and cytoplasmic membrane controls Mg2+ transport
      into the fungal cell. As the strength of this gradient is a function of
      extracellular solution pH, the pH-dependence on Mg isotope fractionation is thus
      due to differences in fungal cell mass fluxes. Through a mass balance model we
      show that Mg uptake into the fungal cell is not associated with a unique Mg
      isotope fractionation factor. This Mg isotope fractionation dependence on pH
      might also be observed in any organism with cells that follow similar Mg uptake
      and metabolic pathways and serves to reveal Mg cycling in ecosystems.

PMID- 28758387
TI  - Characterization of Heme Orientational Disorder in a Myoglobin Reconstituted with
      a Trifluoromethyl-Group-Substituted Heme Cofactor.
AB  - The orientation of a CF3-substituted heme in sperm whale myoglobin and L29F,
      H64L, L29F/H64Q, and H64Q variant proteins has been investigated using 19F NMR
      spectroscopy to elucidate structural factors responsible for the thermodynamic
      stability of the heme orientational disorder, i.e., the presence of two heme
      orientations differing by a 180 degrees  rotation about the 5-15 meso axis, with
      respect to the protein moiety. Crystal structure of the met-aquo form of the wild
      type myoglobin reconstituted with 13,17-bis(2-carboxylatoethyl)-3,8-diethyl
      2,12,18-trimethyl-7-trifluoromethylporphyrinatoiron(III), determined at
      resolution of 1.25 A, revealed the presence of the heme orientational disorder.
      Alterations of the salt bridge between the heme 13-propionate and Arg45(CD3) side
      chains due to the mutations resulted in equilibrium constants of the heme
      orientational disorder ranging between 0.42 and 1.4. Thus, the heme orientational
      disorder is affected by the salt bridge associated with the heme 13-propionate
      side chain, confirming the importance of the salt bridge in the heme binding to
      the protein.

PMID- 28758386
TI  - Active Sites of O2-Evolving Chlorite Dismutases Probed by Halides and Hydroxides
      and New Iron-Ligand Vibrational Correlations.
AB  - O2-evolving chlorite dismutases (Clds) fall into two subfamilies, which
      efficiently convert ClO2- to O2 and Cl-. The Cld from Dechloromonas aromatica
      (DaCld) represents the chlorite-decomposing homopentameric enzymes found in
      perchlorate- and chlorate-respiring bacteria. The Cld from the Gram-negative
      human pathogen Klebsiella pneumoniae (KpCld) is representative of the second
      subfamily, comprising homodimeric enzymes having truncated N-termini. Here steric
      and nonbonding properties of the DaCld and KpCld active sites have been probed
      via kinetic, thermodynamic, and spectroscopic behaviors of their fluorides,
      chlorides, and hydroxides. Cooperative binding of Cl- to KpCld drives formation
      of a hexacoordinate, high-spin aqua heme, whereas DaCld remains pentacoordinate
      and high-spin under analogous conditions. Fluoride coordinates to the heme iron
      in KpCld and DaCld, exhibiting nu(FeIII-F) bands at 385 and 390 cm-1,
      respectively. Correlation of these frequencies with their CT1 energies reveals
      strong H-bond donation to the F- ligand, indicating that atoms directly
      coordinated to heme iron are accessible to distal H-bond donation. New
      vibrational frequency correlations between either nu(FeIII-F) or nu(FeIII-OH) and
      nu(FeII-His) of Clds and other heme proteins are reported. These correlations
      orthogonalize proximal and distal effects on the bonding between iron and
      exogenous pi-donor ligands. The axial Fe-X vibrations and the relationships
      between them illuminate both similarities and differences in the H-bonding and
      electrostatic properties of the distal and proximal heme environments in
      pentameric and dimeric Clds. Moreover, they provide general insight into the
      structural basis of reactivity toward substrates in heme-dependent enzymes and
      their mechanistic intermediates, especially those containing the ferryl moiety.

PMID- 28758388
TI  - High Performance and Enhanced Durability of Thermochromic Films Using VO2@ZnO
      Core-Shell Nanoparticles.
AB  - For VO2-based thermochromic smart windows, high luminous transmittance (Tlum) and
      solar regulation efficiency (DeltaTsol) are usually pursued as the most critical
      issues, which have been discussed in numerous researches. However, environmental
      durability, which has rarely been considered, is also so vital for practical
      application because it determines lifetime and cycle times of smart windows. In
      this paper, we report novel VO2@ZnO core-shell nanoparticles with ultrahigh
      durability as well as improved thermochromic performance. The VO2@ZnO
      nanoparticles-based thermochromic film exhibits a robust durability that the
      DeltaTsol keeps 77% (from 19.1% to 14.7%) after 103 hours in a hyperthermal and
      humid environment, while a relevant property of uncoated VO2 nanoparticles-based
      film badly deteriorates after 30 h. Meanwhile, compared with the uncoated VO2
      based film, the VO2@ZnO-based film demonstrates an 11.0% increase (from 17.2% to
      19.1%) in DeltaTsol and a 31.1% increase (from 38.9% to 51.0%) in Tlum. Such
      integrated thermochromic performance expresses good potential for practical
      application of VO2-based smart windows.

PMID- 28758389
TI  - Competitive and Cooperative Effects during Nickel Adsorption to Iron Oxides in
      the Presence of Oxalate.
AB  - Iron oxides are ubiquitous in soils and sediments and play a critical role in the
      geochemical distribution of trace elements and heavy metals via adsorption and
      coprecipitation. The presence of organic acids may potentially alter how metals
      associate with iron oxide minerals through a series of cooperative or competitive
      processes: solution complexation, ternary surface complexation, and surface site
      competition. The macroscopic and molecular-scale effects of these processes were
      investigated for Ni adsorption to hematite and goethite at pH 7 in the presence
      of oxalate. The addition of this organic acid suppresses Ni uptake on both
      minerals. Aqueous speciation suggests that this is dominantly the result of
      oxalate complexing and solubilizing Ni. Comparison of the Ni surface coverage to
      the concentration of free (uncomplexed) Ni2+ in solution suggests that the
      oxalate also alters Ni adsorption affinity. EXAFS and ATR-FTIR spectroscopies
      indicate that these changes in binding affinity are due to the formation of Ni
      oxalate ternary surface complexes. These observations demonstrate that
      competition between dissolved oxalate and the mineral surface for Ni overwhelms
      the enhancement in adsorption associated with ternary complexation. Oxalate thus
      largely enhances Ni mobility, thereby increasing micronutrient bioavailability
      and inhibiting contaminant sequestration.

PMID- 28758390
TI  - Printable Nanocomposite FeS2-PbS Nanocrystals/Graphene Heterojunction
      Photodetectors for Broadband Photodetection.
AB  - Colloidal nanocrystals are attractive materials for optoelectronics applications
      because they offer a compelling combination of low-cost solution processing,
      printability, and spectral tunability through the quantum dot size effect. Here
      we explore a novel nanocomposite photosensitizer consisting of colloidal
      nanocrystals of FeS2 and PbS with complementary optical and microstructural
      properties for broadband photodetection. Using a newly developed ligand exchange
      to achieve high-efficiency charge transfer across the nanocomposite FeS2-PbS
      sensitizer and graphene on the FeS2-PbS/graphene photoconductors, an
      extraordinary photoresponsivity in exceeding ~106 A/W was obtained in an
      ultrabroad spectrum of ultraviolet (UV)-visible-near-infrared (NIR). This is in
      contrast to the nearly 3 orders of magnitude reduction of the photoresponsivity
      from ~106 A/W at UV to 103 A/W at NIR on their counterpart of FeS2/graphene
      detectors. This illustrates the combined advantages of the nanocomposite
      sensitizers and the high charge mobility in FeS2-PbS/graphene van der Waals
      heterostructures for nanohybrid optoelectronics with high performance, low cost,
      and scalability for commercialization.

PMID- 28758391
TI  - Impact of Microstructure on MoS2 Oxidation and Friction.
AB  - This work demonstrates the role of microstructure in the friction and oxidation
      behavior of the lamellar solid lubricant molybdenum disulfide (MoS2). We report
      on systematic investigations of oxidation and friction for two MoS2 films with
      distinctively different microstructures-amorphous and planar/highly-ordered
      before and after exposure to atomic oxygen (AO) and high-temperature (250 
      degrees C) molecular oxygen. A combination of experimental tribology, molecular
      dynamics simulations, X-ray photoelectron spectroscopy (XPS), and high
      sensitivity low-energy ion scattering (HS-LEIS) was used to reveal new insights
      about the links between structure and properties of these widely utilized low
      friction materials. Initially, ordered MoS2 films showed a surprising resistance
      to both atomic and molecular oxygens (even at elevated temperature), retaining
      characteristic low friction after exposure to extreme oxidative environments. XPS
      shows comparable oxidation of both coatings via AO; however, monolayer resolved
      compositional depth profiles from HS-LEIS reveal that the microstructure of the
      ordered coatings limits oxidation to the first atomic layer.

PMID- 28758392
TI  - Distinct Reactivity of a Mononuclear Peroxocobalt(III) Species toward Activation
      of Nitriles.
AB  - A mononuclear side-on peroxocobalt(III) complex with a tetradentate macrocyclic
      ligand, [CoIII(TBDAP)(O2)]+ (1), shows a novel and facile mode of dioxygenase
      like reactivity with nitriles (R-C=N; R = Me, Et, and Ph) to produce the
      corresponding mononuclear hydroximatocobalt(III) complexes, [CoIII(TBDAP)(R
      C(?NO)O)]+, in which the nitrile moiety is oxidized by two oxygen atoms of the
      peroxo group. The overall reaction proceeds in one-pot under ambient conditions
      (ca. 1 h, 40  degrees C). 18O-Labeling experiments confirm that both oxygen atoms
      are derived from the peroxo ligand. The structures of all products,
      hydroximatocobalt(III) complexes, were confirmed by X-ray crystallography and
      various spectroscopic techniques. Kinetic studies including the Hammett analysis
      and isotope labeling experiments suggest that the mechanistic mode of 1 for
      activation of nitriles occurs via a concerted mechanism. This novel reaction
      would be significantly valuable for expanding the chemistry for nitrile
      activation and utilization.

PMID- 28758393
TI  - GSH-Activated NIR Fluorescent Prodrug for Podophyllotoxin Delivery.
AB  - Theranostic prodrug therapy enables the targeted delivery of anticancer drugs
      with minimized adverse effects and real-time in situ monitoring of activation of
      the prodrugs. In this work, we report the synthesis and biological assessment of
      the near-infrared (NIR) prodrug DCM-S-PPT and its amphiphilic copolymer (mPEG
      DSPE)-encapsulated nanoparticles. DCM-S-PPT is composed of podophyllotoxin (PPT)
      as the anticancer moiety and a dicyanomethylene-4H-pyran (DCM) derivative as the
      NIR fluorescent reporter, which are linked by a thiol-specific cleavable
      disulfide bond. In vitro experiments indicated that DCM-S-PPT has low
      cytotoxicity and that glutathione (GSH) can activate DCM-S-PPT resulting in PPT
      release and a concomitant significant enhancement in NIR fluorescence at 665 nm.
      After being intravenously injected into tumor-bearing nude mice, DCM-S-PPT
      exhibited excellent tumor-activated performance. Furthermore, we have
      demonstrated that mPEG-DSPE as a nanocarrier loaded with DCM-S-PPT (mPEG-DSPE/DCM
      S-PPT) showed even greater tumor-targeting performance than DCM-S-PPT on account
      of the enhanced permeability and retention effect. Its tumor-targeting ability
      and specific drug release in tumors make DCM-S-PPT a promising prodrug that could
      provide a significant strategy for theranostic drug delivery systems.

PMID- 28758394
TI  - Formation of a Crack-Free, Hybrid Skin Layer with Tunable Surface Topography and
      Improved Gas Permeation Selectivity on Elastomers Using Gel-Liquid Infiltration
      Polymerization.
AB  - Surface modifications of elastomers and gels are crucial for emerging
      applications such as soft robotics and flexible electronics, in large part
      because they provide a platform to control wettability, adhesion, and
      permeability. Current surface modification methods via ultraviolet-ozone (UVO)
      and/or O2 plasma, atomic layer deposition (ALD), plasmas deposition, and chemical
      treatment impart a dense polymer or inorganic layer on the surface that is
      brittle and easy to fracture at low strain levels. This paper presents a new
      method, based on gel-liquid infiltration polymerization, to form hybrid skin
      layers atop elastomers. The method is unique in that it allows for control of the
      skin layer topography, with tunable feature sizes and aspect ratios as high as
      1.8 without fracture. Unlike previous techniques, the skin layer formed here
      dramatically improves the barrier properties of the elastomer, while preserving
      skin layer flexibility. Moreover, the method is versatile and likely applicable
      to most interfacial polymerization systems and network polymers on flat and
      patterned surfaces.

PMID- 28758395
TI  - Hydrophilic Phage-Mimicking Membrane Active Antimicrobials Reveal Nanostructure
      Dependent Activity and Selectivity.
AB  - The prevalent wisdom on developing membrane active antimicrobials (MAAs) is to
      seek a delicate, yet unquantified, cationic-hydrophobic balance. Inspired by
      phages that use nanostructured protein devices to invade bacteria efficiently and
      selectively, we study here the antibiotic role of nanostructures by designing
      spherical and rod-like polymer molecular brushes (PMBs) that mimic the two basic
      structural motifs of bacteriophages. Three model PMBs with different well-defined
      geometries consisting of multiple, identical copies of densely packed poly(4
      vinyl-N-methylpyridine iodide) branches are synthesized by controlled/"living"
      polymerization, reminiscent of the viral structural motifs comprised of multiple
      copies of protein subunits. We show that, while the individual linear-chain
      polymer branch that makes up the PMBs is hydrophilic and a weak antimicrobial,
      amphiphilicity is not a required antibiotic trait once nanostructures come into
      play. The nanostructured PMBs induce an unusual topological transition of
      bacterial but not mammalian membranes to form pores. The sizes and shapes of the
      nanostructures further help define the antibiotic activity and selectivity of the
      PMBs against different families of bacteria. This study highlights the importance
      of nanostructures in the design of MAAs with high activity, low toxicity, and
      target specificity.

PMID- 28758397
TI  - Calcium-Mediated Control of S100 Proteins: Allosteric Communication via an
      Agitator/Signal Blocking Mechanism.
AB  - Allosteric proteins possess dynamically coupled residues for the propagation of
      input signals to distant target binding sites. The input signals usually
      correspond to "effector is present" or "effector is not present". Many aspects of
      allosteric regulation remain incompletely understood. This work focused on
      S100A11, a dimeric EF-hand protein with two hydrophobic target binding sites. An
      annexin peptide (Ax) served as the target. Target binding is allosterically
      controlled by Ca2+ over a distance of ~26 A. Ca2+ promotes formation of a [Ca4
      S100 Ax2] complex, where the Ax peptides are accommodated between helices III/IV
      and III'/IV'. Without Ca2+ these binding sites are closed, precluding
      interactions with Ax. The allosteric mechanism was probed by microsecond MD
      simulations in explicit water, complemented by hydrogen exchange mass
      spectrometry (HDX/MS). Consistent with experimental data, MD runs in the absence
      of Ca2+ and Ax culminated in target binding site closure. In simulations on [Ca4
      S100] the target binding sites remained open. These results capture the essence
      of allosteric control, revealing how Ca2+ prevents binding site closure. Both
      HDX/MS and MD data showed that the metalation sites become more dynamic after
      Ca2+ loss. However, these enhanced dynamics do not represent the primary trigger
      of the allosteric cascade. Instead, a labile salt bridge acts as an incessantly
      active "agitator" that destabilizes the packing of adjacent residues, causing a
      domino chain of events that culminates in target binding site closure. This
      agitator represents the starting point of the allosteric signal propagation
      pathway. Ca2+ binding rigidifies elements along this pathway, thereby blocking
      signal transmission. This blocking mechanism does not conform to the commonly
      held view that allosteric communication pathways generally originate at the sites
      where effectors interact with the protein.

PMID- 28758396
TI  - Impact of LCA-Associated E14L LRAT Mutation on Protein Stability and Retinoid
      Homeostasis.
AB  - Vitamin A (all-trans-retinol) is metabolized to the visual chromophore (11-cis
      retinal) in the eyes and to all-trans-retinoic acid, a hormone like compound, in
      most tissues. A key enzyme in retinoid metabolism is lecithin:retinol
      acyltransferase (LRAT), which catalyzes the esterification of vitamin A. The
      importance of LRAT is indicated by pathogenic missense and nonsense mutations,
      which cause devastating blinding diseases. Retinoid-based chromophore replacement
      therapy has been proposed as treatment for these types of blindness based on
      studies in LRAT null mice. Here, we analyzed the structural and biochemical basis
      for retinal pathology caused by mutations in the human LRAT gene. Most LRAT
      missense mutations associated with retinal degeneration are localized within the
      catalytic domain, whereas E14L substitution is localized in an N-terminal alpha
      helix, which has been implicated in interaction with the phospholipid bilayer. To
      elucidate the biochemical consequences of this mutation, we determined
      LRAT(E14L)'s enzymatic properties, protein stability, and impact on ocular
      retinoid metabolism. Bicistronic expression of LRAT(E14L) and enhanced green
      fluorescence protein revealed instability and accelerated proteosomal degradation
      of this mutant isoform. Surprisingly, instability of LRAT(E14L) did not abrogate
      the production of the visual chromophore in a cell-based assay. Instead,
      expression of LRAT(E14L) led to a rapid increase in cellular levels of retinoic
      acid upon retinoid supplementation. Thus, our study unveils the potential role of
      retinoic acid in the pathology of a degenerative retinal disease with important
      implications for the use of retinoid-based therapeutics in affected patients.

PMID- 28758398
TI  - Origin of Fine Particulate Carbon in the Rural United States.
AB  - Carbonaceous compounds are a significant component of fine particulate matter and
      haze in national parks and wilderness areas where visibility is protected, i.e.,
      class I areas (CIAs). The Regional Haze Rule set the goal of returning visibility
      in CIAs on the most anthropogenically impaired days to natural by 2064. To
      achieve this goal, we need to understand contributions of natural and
      anthropogenic sources to the total fine particulate carbon (TC). A Lagrangian
      chemical transport model was used to simulate the 2006-2008 contributions from
      various source types to measured TC in CIAs and other rural lands. These initial
      results were incorporated into a hybrid model to reduce systematic biases. During
      summer months, fires and vegetation-derived secondary organic carbon together
      often accounted for >75% of TC. Smaller contributions, <20%, from area and mobile
      sources also occurred. During the winter, contributions from area and mobile
      sources increased, with area sources accounting for half or more of the TC in
      many regions. The area emissions were likely primarily from residential and
      industrial wood combustion. Different fire seasons were evident, with the largest
      contributions during the summer when wildfires occur and smaller contributions
      during the spring and fall when prescribed and agricultural fires regularly
      occur.

PMID- 28758399
TI  - Surface Heterostructure Induced by PrPO4 Modification in
      Li1.2[Mn0.54Ni0.13Co0.13]O2 Cathode Material for High-Performance Lithium-Ion
      Batteries with Mitigating Voltage Decay.
AB  - Lithium-rich layered oxides (LLOs) have been attractive cathode materials for
      lithium-ion batteries because of their high reversible capacity. However, they
      suffer from low initial Coulombic efficiency and capacity/voltage decay upon
      cycling. Herein, facile surface modification of Li1.2Mn0.54Ni0.13Co0.13O2 cathode
      material is designed to overcome these defects by the protective effect of a
      surface heterostructure composed of an induced spinel layer and a PrPO4
      modification layer. As anticipated, a sample modified with 3 wt % PrPO4 (PrP3)
      shows an enhanced initial Coulombic efficiency of 90% compared to 81.8% for the
      pristine one, more excellent cycling stability with a capacity retention of 89.3%
      after 100 cycles compared to only 71.7% for the pristine one, and less average
      discharge voltage fading from 0.6353 to 0.2881 V. These results can be attributed
      to the fact that the modification nanolayers have moved amounts of oxygen and
      lithium from the lattice in the bulk crystal structure, leading to a chemical
      activation of the Li2MnO3 component previously and forming a spinel interphase
      with a 3D fast Li+ diffusion channel and stable structure. Moreover, the
      elaborate surface heterostructure on a lithium-rich cathode material can
      effectively curb the undesired side reactions with the electrolyte and may also
      extend to other layered oxides to improve their cycling stability at high
      voltage.

PMID- 28758400
TI  - Can COSMOTherm Predict a Salting in Effect?
AB  - We have used COSMO-RS, a method combining quantum chemistry with statistical
      thermodynamics, to compute Setschenow constants (KS) for a large array of organic
      solutes and salts. These comprise both atmospherically relevant solute-salt
      combinations, as well as systems for which experimental data are available. In
      agreement with previous studies on single salts, the Setschenow constants
      predicted by COSMO-RS (as implemented in the COSMOTherm program) are generally
      too large compared to experiments. COSMOTherm overpredicts salting out (positive
      KS), and/or underpredicts salting in (negative KS). For ammonium and sodium
      salts, KS values are larger for oxalates and sulfates, and smaller for chlorides
      and bromides. For chloride and bromide salts, KS values usually increase with
      decreasing size of the cation, along the series Pr4N+ < Et4N+ < Me4N+ <= Na+ ~
      NH4+. Of the atmospherically relevant systems studied, salting in is predicted
      only for oxalic acid in sodium and ammonium oxalate, and sodium sulfate,
      solutions. COSMOTherm was thus unable to replicate the experimentally observed
      salting in of glyoxal in sulfate solutions, likely due to the overestimation of
      salting out effects. By contrast, COSMOTherm does qualitatively predict the
      experimentally observed salting in of multiple organic solutes in solutions of
      alkylaminium salts.

PMID- 28758401
TI  - Growth of Pure Zinc-Blende GaAs(P) Core-Shell Nanowires with Highly Regular
      Morphology.
AB  - The growth of self-catalyzed core-shell nanowires (NWs) is investigated
      systematically using GaAs(P) NWs. The defects in the core NW are found to be
      detrimental for the shell growth. These defects are effectively eliminated by
      introducing beryllium (Be) doping during the NW core growth and hence forming Be
      Ga alloy droplets that can effectively suppress the WZ nucleation and facilitate
      the droplet consumption. Shells with pure zinc-blende crystal quality and highly
      regular morphology are successfully grown on the defect-free NW cores and
      demonstrated an enhancement of one order of magnitude for room-temperature
      emission compared to that of the defective shells. These results provide useful
      information on guiding the growth of high-quality shell, which can greatly
      enhance the NW device performance.

PMID- 28758402
TI  - Nanoscopic Study on Aliphatic Choline-Based Naphthenic Acid Ionic Liquids:
      Structural and Dynamical Properties.
AB  - The structural and dynamical properties of two cholinium-based naphthenic acid
      ionic liquids (CBNAILs), namely, cholinium cyclopentane carboxylate ([CH][CPC])
      and cholinium cyclohexane carboxylate ([CH][CHC]) have been studied using the
      classical molecular dynamics simulations and quantum mechanical methods. The
      results have also been compared with corresponding aromatic ones. Interaction
      energies, charge transfers, and hydrogen bondings between the studied ion pairs
      were investigated by density functional theory calculations and also the theory
      of atoms in molecules. Density, mean-square displacement, self-diffusivity,
      viscosity, electrical conductivity, transference number, ionicity, and fragility
      have been computed for the studied CBNAILs in the temperature range of 298.15-450
      K and at 0.1 MPa. The simulated values were in good agreement with experimental
      data where they exist. The structural features of these CBNAILs were
      characterized by calculating the partial site-site radial distribution functions
      and spatial distribution functions. The results show a density cap of hydrogen
      atoms of hydroxyl groups of cations extended along the COO- groups of anions. In
      these ILs, [CPC]- and [CHC]- are connected by hydrogen bonding to [CH]+ mainly
      through the carboxylate group. Increasing the number of carbon atoms in the ring
      of [CHC]- with respect to [CPC]- makes remarkable changes in self-diffusions,
      electrical conductivities, and viscosities. Altogether, this work gives a better
      insight into the dynamics and structuring of this class of biodegradable ILs at a
      molecular level.

PMID- 28758403
TI  - Ab Initio Computations and Active Thermochemical Tables Hand in Hand: Heats of
      Formation of Core Combustion Species.
AB  - The fidelity of combustion simulations is strongly dependent on the accuracy of
      the underlying thermochemical properties for the core combustion species that
      arise as intermediates and products in the chemical conversion of most fuels.
      High level theoretical evaluations are coupled with a wide-ranging implementation
      of the Active Thermochemical Tables (ATcT) approach to obtain well-validated high
      fidelity predictions for the 0 K heat of formation for a large set of core
      combustion species. In particular, high level ab initio electronic structure
      based predictions are obtained for a set of 348 C, N, O, and H containing
      species, which corresponds to essentially all core combustion species with 34 or
      fewer electrons. The theoretical analyses incorporate various high level
      corrections to base CCSD(T)/cc-pVnZ analyses (n = T or Q) using H2, CH4, H2O, and
      NH3 as references. Corrections for the complete-basis-set limit, higher-order
      excitations, anharmonic zero-point energy, core-valence, relativistic, and
      diagonal Born-Oppenheimer effects are ordered in decreasing importance.
      Independent ATcT values are presented for a subset of 150 species. The accuracy
      of the theoretical predictions is explored through (i) examination of the
      magnitude of the various corrections, (ii) comparisons with other high level
      calculations, and (iii) through comparison with the ATcT values. The estimated
      2sigma uncertainties of the three methods devised here, ANL0, ANL0-F12, and ANL1,
      are in the range of +/-1.0-1.5 kJ/mol for single-reference and moderately
      multireference species, for which the calculated higher order excitations are 5
      kJ/mol or less. In addition to providing valuable references for combustion
      simulations, the subsequent inclusion of the current theoretical results into the
      ATcT thermochemical network is expected to significantly improve the
      thermochemical knowledge base for less-well studied species.

PMID- 28758404
TI  - Lycopene Prevents Mitochondrial Dysfunction during d
      Galactosamine/Lipopolysaccharide-Induced Fulminant Hepatic Failure in Albino
      Rats.
AB  - Functional perturbation of mitochondria is associated with fulminant hepatic
      failure (FHF). d-Galactosamine/lipopolysaccharide (d-GalN/LPS)-induced FHF is a
      renowned model to evaluate the efficacy of hepatoprotective agents. Lycopene is
      an antioxidant and phytonutrient from the carotenoid family. The health benefits
      of lycopene are prominent against cancer and cardiovascular, lung, liver, and
      skin problems. Recent studies have demonstrated the hepatoprotective,
      antidyslipidemic, and antioxidant roles of lycopene. The current study was
      designed to appraise the ability of lycopene to prevent mitochondrial dysfunction
      during the d-GalN/LPS-induced FHF. The administration of d-GalN/LPS (300 mg and
      30 MUg/kg body weight, respectively) to the experimental rats induced several
      disturbances in mitochondrial function. The lipid peroxide and hydrogen peroxide
      levels were increased (p < 0.05). The activities of mitochondrial antioxidants,
      tricarboxylic acid (TCA) cycle, and electron transport chain enzymes and the
      cellular adenosine triphosphate (ATP) content were decreased (p < 0.05). Lycopene
      (10 mg/kg body weight for 6 days) pretreatment attenuated lipid peroxidation and
      prohibited the excessive synthesis of hydrogen peroxide. The d-GalN/LPS-induced
      impairment in ATP production and increased enzyme activities were effectively
      prevented by the lycopene administration. The lycopene-mediated mitochondrial
      protection was mainly ascribed to the strong antioxidant potential of this
      phytonutrient. Molecular modeling results obtained show evidence that lycopene
      inhibits several lipoxygenases and provides rationale for the observed prevention
      of lipid peroxidation in the mitochondrial membrane. The carotenoid lycopene
      combatted oxidative stress, scavenged free radicals, prevented ROS generation,
      and inhibited the toxic effects of d-GalN/LPS during FHF.

PMID- 28758406
TI  - Meningioma research-status quo and quo vadis.

PMID- 28758407
TI  - Radiation for skull base meningiomas: review of the literature on the approach to
      radiotherapy.
AB  - Skull base meningiomas (SBM) pose unique challenges for radiotherapy as these
      tumors are often in close proximity to a number of critical structures and may
      not be surgically addressed in many cases, leaving the question about the tumor
      grade and expected biological behaviour. External beam radiotherapy and
      radiosurgery are longstanding treatments for meningioma that are typically used
      as upfront primary therapy, for recurrent tumors and as adjuvant therapy
      following surgical resection. There is controversy regarding the optimal timing
      and approach for radiation therapy in various clinical settings such as the role
      of adjuvant radiotherapy for completely resected grade 2 tumours. Despite the use
      of radiotherapy for many decades, the evidence to guide optimal radiation
      treatment is limited largely to single institution series of EBRT, SRS and
      particle therapy. In this article, we review the published data to clarify the
      role of external beam radiotherapy, proton radiotherapy and single and multi
      fraction radiosurgery for SBM. We also highlight the areas of potential research
      and need for clinical improvement, including the growing awareness and effort to
      improve cognitive function in this patient population, who typically have long
      life expectancy following their meningioma diagnosis.

PMID- 28758408
TI  - Radiation therapy for WHO grade I meningioma.
AB  - Maximal safe resection has long been the cornerstone of treatment for WHO grade I
      benign meningioma. However, as technology for both imaging and radiation delivery
      has advanced, radiation therapy has played an increasingly important role in the
      management of patients with WHO grade I meningioma. Radiation therapy, whether
      delivered as standard fractionated treatment over several weeks, stereotactic
      radiosurgery over 1 session, or multisession stereotactic radiation therapy, has
      been shown to provide excellent local control when used as an adjunct to surgery
      or as primary treatment. Here, we review the indications for radiation therapy
      for patients with WHO grade I meningioma, as well as the various techniques that
      have been developed. We also review the toxicities and late effects associated
      with treatment.

PMID- 28758409
TI  - The role of radiotherapy in the management of high-grade meningiomas.
AB  - Meningiomas account for approximately one-third of primary central nervous system
      tumors with a subset that are aggressive and carry significant morbidity and
      mortality. Treatment of these high-grade meningiomas, classified by the World
      Health Organization as grade II (atypical) and grade III (anaplastic)
      meningiomas, typically includes the combination of surgery and radiotherapy.
      However, current data guiding the timing, dosage, and modality of radiation
      treatment (RT) has been limited to case series and retrospective studies.
      Nevertheless, most studies support that radiation therapy reduces recurrence risk
      and improves overall survival (OS) for patients with high-grade meningiomas. In
      this review, we examine the evidence for radiation therapy in the management of
      patients with atypical and anaplastic meningiomas and discuss current ongoing
      prospective trials that will further elucidate the optimal role of radiotherapy
      in the treatment of these aggressive tumors.

PMID- 28758410
TI  - Current and emerging principles in surgery for meningioma.
AB  - Surgery continues to be the preferred method to treat meningioma. Recent
      advancements in the understanding of meningioma biology, including a new
      appreciation for remarkable molecular heterogeneity in these tumors, has
      sharpened the drive for disease control, especially on initial diagnosis.
      Microsurgical and skull base techniques and principles dominate the surgical
      approaches for meningiomas. At the same time, biologic tools may improve the
      extent of surgical resection as well as provide novel adjuvant therapy options
      for challenging meningiomas.

PMID- 28758411
TI  - Contemporary Demographic, Treatment, and Geographic Distribution Patterns for
      Disorders of Sex Development.
AB  - This study aimed to describe the demographic characteristics, hospital
      utilizations, patterns of inpatient surgical management, and the overall
      state/regional variation in surgery rate among patients with disorders of sex
      development (DSD). We analyzed the Nationwide Inpatient Sample from 2001 to 2012
      for patients younger than 21 years. DSD-related diagnoses and procedures were
      identified via International Classification of Diseases, Ninth Revision (ICD-9)
      codes. We identified a total of 43,968 DSD-related admissions. Of these, 73.4% of
      the admissions were designated as female and 642 (1.9%) were inpatient surgical
      admissions. Among neonates, less than 1% underwent any type of genital surgery.
      Nonsurgical admissions were associated with longer length of stay and higher
      cost. There was no significant regional variation in the rate of DSD surgeries,
      but we observed higher concentrations of DSD surgeries in states associated with
      tertiary referral centers.

PMID- 28758405
TI  - Blood Metabolic Signatures of Body Mass Index: A Targeted Metabolomics Study in
      the EPIC Cohort.
AB  - Metabolomics is now widely used to characterize metabolic phenotypes associated
      with lifestyle risk factors such as obesity. The objective of the present study
      was to explore the associations of body mass index (BMI) with 145 metabolites
      measured in blood samples in the European Prospective Investigation into Cancer
      and Nutrition (EPIC) study. Metabolites were measured in blood from 392 men from
      the Oxford (UK) cohort (EPIC-Oxford) and in 327 control subjects who were part of
      a nested case-control study on hepatobiliary carcinomas (EPIC-Hepatobiliary).
      Measured metabolites included amino acids, acylcarnitines, hexoses, biogenic
      amines, phosphatidylcholines, and sphingomyelins. Linear regression models
      controlled for potential confounders and multiple testing were run to evaluate
      the associations of metabolite concentrations with BMI. 40 and 45 individual
      metabolites showed significant differences according to BMI variations, in the
      EPIC-Oxford and EPIC-Hepatobiliary subcohorts, respectively. Twenty two
      individual metabolites (kynurenine, one sphingomyelin, glutamate and 19
      phosphatidylcholines) were associated with BMI in both subcohorts. The present
      findings provide additional knowledge on blood metabolic signatures of BMI in
      European adults, which may help identify mechanisms mediating the relationship of
      BMI with obesity-related diseases.

PMID- 28758412
TI  - Onset of decreased heart work is correlated with increased heart rate and
      shortened QT interval in high-carbohydrate fed overweight rats.
AB  - Mechanical activity of the heart is adversely affected in metabolic syndrome
      (MetS) characterized by increased body mass and marked insulin resistance.
      Herein, we examined the effects of high carbohydrate intake on cardiac function
      abnormalities by evaluating in situ heart work, heart rate, and
      electrocardiograms (ECGs) in rats. MetS was induced in male Wistar rats by adding
      32% sucrose to drinking water for 22-24 weeks and was confirmed by insulin
      resistance, increased body weight, increased blood glucose and serum insulin, and
      increased systolic and diastolic blood pressures in addition to significant loss
      of left ventricular integrity and increased connective tissue around myofibrils.
      Analysis of in situ ECG recordings showed a markedly shortened QT interval and
      decreased QRS amplitude with increased heart rate. We also observed increased
      oxidative stress and decreased antioxidant defense characterized by decreases in
      serum total thiol level and attenuated paraoxonase and arylesterase activities.
      Our data indicate that increased heart rate and a shortened QT interval
      concomitant with higher left ventricular developed pressure in response to beta
      adrenoreceptor stimulation as a result of less cyclic AMP release could be
      regarded as a natural compensation mechanism in overweight rats with MetS. In
      addition to the persistent insulin resistance and obesity associated with MetS,
      one should consider the decreased heart work, increased heart rate, and shortened
      QT interval associated with high carbohydrate intake, which may have more
      deleterious effects on the mammalian heart.

PMID- 28758413
TI  - Determination of Magnesium Oxide Content in Mineral Medicine Talcum Using Near
      Infrared Spectroscopy Integrated with Support Vector Machine.
AB  - In this research paper, a fast, quantitative, analytical model for magnesium
      oxide (MgO) content in medicinal mineral talcum was explored based on near
      infrared (NIR) spectroscopy. MgO content in each sample was determined by
      ethylenediaminetetraacetic acid (EDTA) titration and taken as reference value of
      NIR spectroscopy, and then a variety of processing methods of spectra data were
      compared to establish a good NIR spectroscopy model. To start, 50 batches of
      talcum samples were categorized into training set and test set using the Kennard
      Stone (K-S) algorithm. In a partial least squares regression (PLSR) model, both
      leave-one-out cross-validation (LOOCV) and training set validation (TSV) were
      used to screen spectrum preprocessing methods from multiplicative scatter
      correction (MSC), and finally the standard normal variate transformation (SNV)
      was chosen as the optimal pretreatment method. The modeling spectrum bands and
      ranks were optimized using PLSR method, and the characteristic spectrum ranges
      were determined as 11995-10664, 7991-6661, and 4326-3999 cm-1, with four optimal
      ranks. In the support vector machine (SVM) model, the radical basis function
      (RBF) kernel function was used. Moreover, the full spectrum data of samples
      pretreated with SNV, the characteristic spectrum data screened using synergy
      interval partial least squares (SiPLS), and the scoring data of the first four
      ranks obtained by a partial least squares (PLS) dimension reduction of
      characteristic spectrum were taken as input variables of SVM, and the MgO content
      reference values of various sample were taken as output values. In addition, the
      SVM model internal parameters were optimized using the grid optimization method
      (GRID), particle swarm optimization (PSO), and genetic algorithm (GA) so that the
      optimal C and g-values were determined and the validation model was established.
      By comprehensively comparing the validation effects of different models, it can
      be concluded that the scoring data of the first four ranks obtained by PLS
      dimension reduction of characteristic spectrum were taken as input variables of
      SVM, and the PLS-SVM regression model established using GRID was the optimal NIR
      spectroscopy quantitative model of talc. This PLS-SVM regression model (rank = 4)
      measured that the MgO content of talcum was in the range of 17.42-33.22%, with
      root mean square error of cross validation (RMSECV) of 2.2127%, root mean square
      error of calibration (RMSEC) of 0.6057%, and root mean square error of prediction
      (RMSEP) of 1.2901%. This model showed high accuracy and strong prediction
      capacity, which can be used for rapid prediction of MgO content in talcum.

PMID- 28758414
TI  - Modulation of N-methyl-d-aspartate receptors in isolated rat heart.
AB  - Considering the limited data on the role of NMDA-Rs in the cardiovascular system,
      the aim of the present study was to examine the effects of NMDA and DL-Hcy TLHC,
      alone and in combination with glycine, memantine, and ifenprodil, in the isolated
      rat heart. The hearts of Wistar albino rats were retrogradely perfused according
      to the Langendorff technique at a constant perfusion pressure. The experimental
      protocol for all experimental groups included the stabilization period,
      application of estimated substance for 5 min, followed by a washout period of 10
      min. Using a sensor placed in the left ventricle, we registered the following
      parameters of myocardial function: dp/dtmax, dp/dtmin, SLVP, DVLP, HR; CF was
      measured using flowmetry). We estimated the following oxidative stress biomarkers
      in the coronary venous effluent using spectrophotometry: TBARS, NO2-, O2-, and
      H2O2. NMDA alone did not induce any change in any of the observed parameters,
      while DL-Hcy TLHC alone, as well as a combined application of NMDA and DL-Hcy
      TLHC with glycine, induced a reduction of most cardiodynamic parameters.
      Memantine and ifenprodil induced a reduction of cardiodynamic parameters and CF,
      as well as some oxidative stress biomarkers.

PMID- 28758416
TI  - Pregnancy outcome after anti-migraine triptan use: A prospective observational
      cohort study.
AB  - Objective The objective of our study is to assess the impact of triptan exposure
      on pregnancy outcome. Methods We performed a prospective observational cohort
      study with 432 pregnant women exposed to triptans and enrolled by the German
      Embryotox system. Pregnancy outcomes were compared with a migraine and a non
      migraine comparison cohort. Primary objectives were major birth defects and
      spontaneous abortion; secondary endpoints were preterm delivery, birth weight,
      pregnancy complications and the rate of electively terminated pregnancies.
      Results Compared to a non-migraine cohort the rates of major birth defects (ORadj
      0.84; 95% CI 0.4-1.9), spontaneous abortions (ORadj 1.20; 95% CI 0.9-1.7),
      preterm delivery (ORadj 1.01; 95% CI 0.7-1.5), and preeclampsia (ORadj 1.33; 95%
      CI 0.7-2.5) were not increased in triptan-exposed pregnancies. Conclusions Our
      findings support the evidence that triptans are not major teratogens. When
      compellingly needed during pregnancy, sumatriptan as the best studied triptan
      appears an acceptable treatment option. A detailed fetal ultrasound should be
      offered in cases of first trimester exposure to less well-studied triptans. Trial
      registration number in German Clinical Trials Register: DRKS00007660.

PMID- 28758415
TI  - Utilization and safety of onabotulinumtoxinA for the prophylactic treatment of
      chronic migraine from an observational study in Europe.
AB  - Objective To examine treatment utilization patterns and safety of
      onabotulinumtoxinA for the prophylactic treatment of chronic migraine in routine
      clinical practice. Background Clinical trials support onabotulinumtoxinA for the
      prophylaxis of headache in patients with chronic migraine, but real-world data
      are limited. Design/methods A prospective, observational, post-authorization
      study in adult patients with chronic migraine treated with onabotulinumtoxinA.
      Data were collected at the first study injection and approximately every three
      months for <=52 weeks for utilization and <=64 weeks for safety data, and
      summarized using descriptive statistics. Results Eighty-five physicians (81%
      neurologists) at 58 practices in the United Kingdom, Germany, Spain, and Sweden
      participated and recruited 1160 patients (84.2% female, median age 46.6 years).
      At baseline, 85.8% of patients had physician diagnoses of chronic
      migraine/transformed migraine and reported an average of 11.3 (SD = 6.9) severe
      headache days per 28 days; 50.6% had previously used onabotulinumtoxinA for
      chronic migraine. A total of 4017 study treatments were observed. The median
      number of injection sites (n = 31) and total dose (155 U) were consistent across
      all treatment sessions, with a median 13.7 weeks observed between sessions. At
      least one treatment-related adverse event was reported by 291 patients (25.1%);
      the most frequently reported treatment-related adverse event was neck pain
      (4.4%). Most patients (74.4%) were satisfied/extremely satisfied with
      onabotulinumtoxinA treatment. Conclusions Patient demographics/characteristics
      are consistent with published data on the chronic migraine population.
      Utilization of onabotulinumtoxinA treatment for chronic migraine appears to be
      consistent with the Summary of Product Characteristics and published PREEMPT
      injection paradigm. No new safety signals were identified.

PMID- 28758417
TI  - Evaluating Longitudinal Invariance in Dimensions of Mental Health Across
      Adolescence: An Analysis of the Social Behavior Questionnaire.
AB  - Measurement invariance over time (longitudinal invariance) is a core but seldom
      tested assumption of many longitudinal studies on adolescent psychosocial
      development. In this study, we evaluated the longitudinal invariance of a brief
      measure of adolescent mental health: the Social Behavior Questionnaire (SBQ). The
      SBQ was administered to participants of the Zurich Project on the Social
      Development of Children and Youths in up to four waves spanning ages 11 to 17.
      Using a confirmatory factor analysis approach, metric invariance held for all
      constructs, but there were some violations of scalar and strict invariance.
      Overall, intercepts tended to increase over time while residual variances
      decreased. This suggests that participants may become more willing or able to
      identify and report on certain behaviors over time. The noninvariance was not
      practically significant in magnitude, except for the Anxiety dimension where
      artifactual increases over development would be liable to occur if invariance is
      not appropriately modeled. Overall, results support the utility of the SBQ as an
      omnibus measure of psychosocial health across adolescence.

PMID- 28758419
TI  - The impact of drop-out in cardiac rehabilitation on outcome among coronary artery
      disease patients.
AB  - Background The effect of adherence to cardiac rehabilitation (CR) on outcome is
      not clear. Therefore, we aimed to assess the impact of drop-out for non-medical
      reasons of CR on event-free survival in coronary artery disease (CAD). Methods A
      total of 876 patients who attended CR after acute coronary syndrome (ACS),
      percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)
      were included. Drop-out was defined as attending <=50% of the training sessions.
      A combined endpoint of all-cause mortality and rehospitalization for a
      cardiovascular event was used to specify event-free survival. Differences in
      clinical characteristics were assessed and parameters with p < 0.10 were entered
      in a multiple Cox regression analysis. Results A total of 15% died or had a
      cardiovascular event during a median follow-up period of 33 months (interquartile
      range 24, 51). Overall, 17% dropped out before finishing half of the program.
      Patients who withdrew prematurely had a risk twice as high for a cardiovascular
      event or death (hazard ratio 1.92, 95% confidence interval 1.28-2.90) than those
      who attended more than half of the sessions. Both ACS (2.36, 1.47-3.58) and PCI
      (2.20, 1.22-3.96), as primary indicators for CR, were associated with an adverse
      outcome and also a prior history of chronic heart failure (CHF) remained
      negatively associated with event-free survival (3.67, 1.24-10.91). Finally, the
      presence of hyperlipidemia was independently related to a worse outcome (1.48,
      1.02-2.16). Conclusions Drop-out for non-medical reasons was independently
      associated with a negative outcome in CAD. Therefore, underlying factors for drop
      out should gain more attention in future research and should be taken into
      account when organizing CR.

PMID- 28758418
TI  - Intermittent hypoxia training in prediabetes patients: Beneficial effects on
      glucose homeostasis, hypoxia tolerance and gene expression.
AB  - The present study aimed at examining beneficial effects of intermittent hypoxia
      training (IHT) under prediabetic conditions. We investigate the effects of three
      week IHT on blood glucose level, tolerance to acute hypoxia, and leukocyte mRNA
      expression of hypoxia inducible factor 1alpha (HIF-1alpha) and its target genes,
      i.e. insulin receptor, facilitated glucose transporter-solute carrier family-2,
      and potassium voltage-gated channel subfamily J. Seven healthy and 11 prediabetic
      men and women (44-70 years of age) were examined before, next day and one month
      after three-week IHT (3 sessions per week, each session consisting 4 cycles of 5
      min 12% O2 and 5-min room air breathing). We found that IHT afforded beneficial
      effects on glucose homeostasis in patients with prediabetes reducing fasting
      glucose and during standard oral glucose tolerance test. The most pronounced
      positive effects were observed at one month after IHT termination. IHT also
      significantly increased the tolerance to acute hypoxia (i.e. SaO2 level at 20th
      min of breathing with 12% O2) and improved functional parameters of respiratory
      and cardiovascular systems. IHT stimulated HIF-1alpha mRNA expression in blood
      leukocytes in healthy and prediabetic subjects, but in prediabetes patients the
      maximum increase was lagged. The greatest changes in mRNA expression of HIF
      1alpha target genes occurred a month after IHT and coincided with the largest
      decrease in blood glucose levels. The higher expression of HIF-1alpha was
      positively associated with higher tolerance to hypoxia and better glucose
      homeostasis. In conclusion, our results suggest that IHT may be useful for
      preventing the development of type 2 diabetes. Impact statement The present study
      investigated the beneficial effects of intermittent hypoxia training (IHT) in
      humans under prediabetic conditions. We found that three-week moderate IHT
      induced higher HIF-1alpha mRNA expressions as well as its target genes, which
      were positively correlated with higher tolerance to acute hypoxia and better
      glucose homeostasis in both middle-aged healthy and prediabetic subjects. This
      small clinical trial has provided new data suggesting a potential utility of IHT
      for management of prediabetes patients.

PMID- 28758420
TI  - MiR-377 reverses cancerous phenotypes of pancreatic cells via suppressing DNMT1
      and demethylating tumor suppressor genes.
AB  - AIM: The aim was to investigate the effect of miR-377 on DNMT1 expression and
      cancer phenotype in pancreatic cancer cells. MATERIALS & METHODS: Real-time PCR,
      luciferase assay, MTT and Annexin-PI staining were used. RESULTS: Decreased miR
      377 and increased DNMT1 (verified as a target for mir-377) levels in pancreatic
      cancer tissues and cell lines in comparison with normal tissues was confirmed to
      be influenced by promoter methylation. Also hypermethylation of BNIP3, SPARC,
      TFPI2 and PENK promoters was observed in tumor samples but not in normal tissues
      which negatively correlated with their expression. Restoration of miR-377
      resulted in a reduction of the expression of DNMT1 and reactivation of BNIP3 and
      SPARC genes via promoter demethylation. Furthermore, enhanced expression of miR
      377 could significantly inhibit cell proliferation and induce apoptosis.
      CONCLUSION: Our findings showed that miR-377 through targeting DNMT1 could reduce
      DNA methylation of some tumor suppressor genes and restore their expression in
      pancreatic cancer cells.

PMID- 28758421
TI  - PCSK9 deficiency results in increased ectopic fat accumulation in experimental
      models and in humans.
AB  - Background Proprotein convertase subtilisin kexin type 9 (PCSK9) regulates low
      density lipoprotein and very low-density lipoprotein receptor expression in
      several tissues. Here we evaluated whether PCSK9 may modulate the handling of
      triglycerides in the liver and peripheral tissues. Methods Subjects from the PLIC
      cohort were genotyped for the loss-of-function PCSK9 R46L variant and
      characterized for clinical and biochemical parameters, total and android fat
      mass, hepatic steatosis and epicardial fat thickness. Visceral adipose tissue and
      subcutaneous adipose tissue in PCSK9 KO and wild type mice were quantified by
      nuclear magnetic resonance imaging. Results Carriers of the R46L variant ( n =
      13) had lower low-density lipoprotein cholesterol levels, higher body mass index
      and increased percentage of total and android fat masses compared with non
      carriers ( n = 521). R46L variant associated with a two-fold increase prevalence
      of hepatic steatosis and higher epicardial fat thickness. These observations were
      replicated in PCSK9 KO mice, which showed increased visceral adipose tissue (but
      not subcutaneous adipose tissue) when fed chow or high-fat diet for 20 weeks,
      compared with wild type mice. Conclusions These data suggest that genetically
      determined PCSK9 deficiency might be associated with ectopic fat accumulation.

PMID- 28758422
TI  - Biomechanical Study of Screw Fixation and Plate Fixation of a Posterior Malleolar
      Fracture in a Simulation of the Normal Gait Cycle.
AB  - BACKGROUND: Fixation of posterior malleolar fractures with plates or screws is
      under debate. A fatigue loading system and a spatial motion capture system were
      used in this study to evaluate a posterior malleolar fracture model. METHODS:
      Thirty-six below-knee specimens with a single posterolateral fragment (Haraguchi
      I) type posterior malleolar fracture models were randomly divided into 2 groups.
      Two parallel-placed 3.5-mm partially threaded titanium alloy screws were used in
      Group A to fix the fractures, while anatomical plates were used in Group B.
      According to the ratio (S) of the area between the fracture and the total
      articular surface, each group was subdivided into 3 subgroups. In group A1 and
      B1, S=1/4; in A2 and B2, S=1/3; and in A3 and B3, S=1/2. To simulate the gait
      cycle, each specimen was subjected to mechanical loading in 4 different ankle
      positions. A fatigue loading system was used for repeated loading. A spatial
      motion capture system was used to measure the displacement in the final loading
      stage. RESULTS: Despite the limited sample size and relatively low power, no
      significant difference was observed between A1 and B1, A2 and B2, and A3 and B3
      in all 4 ankle positions after repeated loading. CONCLUSION: For a Haraguchi type
      I posterior malleolar fracture with an average height of 19 mm, fixation with a
      posterior malleolar anatomical plate failed to demonstrate a stronger strength
      than 2 parallel-placed 3.5-mm partially threaded screws, which indicates that
      plates may not be absolutely necessary for standard rehabilitation after
      posterior malleolar internal fixation. CLINICAL RELEVANCE: These findings may
      help guide surgeons with regard to fixation requirements for posterior malleolar
      fractures.

PMID- 28758423
TI  - Factors Influencing the Prevalence of Stunting Among Children Aged Below Five
      Years in Bangladesh.
AB  - BACKGROUND: Poor nutrition during childhood impedes physical and mental
      development of children, which propagate the vicious cycle of intergenerational
      under nutrition. This paper is aimed at understanding the determinants of
      stunting among children aged 0 to 59 months in Bangladesh. METHODS: The study
      used Bangladesh Demographic and Health Survey 2011 data and a multistage
      stratified cluster-sampling design. Anthropometric data (for height and weight)
      were collected and analysis was limited to 7647 children. Multiple binary
      logistic regression analysis was performed to assess the association of stunting
      with potential socioeconomic and demographic factors. RESULTS: The prevalence of
      stunting has been found to be about 41% among children aged less than 60 months
      and higher in rural setting than in urban areas (43% vs 36%). Adjusted model
      revealed that several factors were influencing stunting. The children living in
      moderately food-insecure households had higher odds of becoming stunted (odds
      ratio [OR] = 1.27, 95% confidence interval [CI]: 1.05-1.54, P = .01) compared to
      the children living in food-secure households. The derived ORs of stunting for
      children delivered at institutions facilitated particularly by public (OR = 0.80,
      95% CI: 0.67-0.96; P = .02) or private (OR = 0.81, 95% CI: 0.67-0.97; P = .02)
      sectors were less than for children delivered at home. Similarly, wealth index,
      exposure of mother to the mass media, age of child, size of child at birth, and
      parents' education were significantly associated with stunting. CONCLUSIONS:
      Moreover, the demographic characteristics and other indicators appeared to have
      significant influence in the prevalence of stunting. Public health programs are
      needed to avert the risk factors of stunting among children in Bangladesh.

PMID- 28758424
TI  - Ribociclib for the treatment of advanced hormone receptor-positive, HER2-negative
      breast cancer.
AB  - CDK4/6 inhibitors are a promising new class of drugs for hormone-receptor
      positive breast cancer and have been shown to overcome and delay hormone
      resistance in advanced breast cancer. Ribociclib, a selective oral inhibitor of
      CDK4/6, was approved by the US FDA for first-line treatment of hormone-receptor
      positive/HER2-negative metastatic breast cancer. This review summarizes the
      clinical evidence available for ribociclib, from preclinical data to the pivotal
      studies, with a special focus on toxicity and its management. In addition, this
      article reviews potential new combinations under study, as well as ongoing
      clinical trials both in the metastatic and early setting. Finally, this review
      compares ribociclib activity and toxicity with those of the drugs of the same
      class (palbociclib and abemaciclib).

PMID- 28758425
TI  - New triterpenoid saponins from the steaming treated roots of Panax notoginseng.
AB  - Further phytochemical investigation of the steaming treated roots of Panax
      notoginseng (Araliaceae) led to the identification of two new dammarane-type
      triterpenoid saponins, notoginsenoside SP20 (1) and SP21 (2). In addition, a pair
      of new phenolic glycosides (3a and 3b) was also isolated together with two known
      compounds. Their structures were elucidated by HRESIMS, 1D- and 2D-NMR spectra.
      Compounds 1 and 2 showed no in vitro cytotoxicity against five human cancer cell
      lines (HL-60, SMMC-7712, A-549, MCF-9 and SW480).

PMID- 28758426
TI  - Evaluation of in vivo analgesic activity of Scrophularia kotscyhana and isolation
      of bioactive compounds through activity-guided fractionation.
AB  - The present study was undertaken to evaluate the in vivo analgesic activities of
      the extracts prepared from the aerial parts and roots of Scrophularia kotscyhana
      and to isolate the bioactive metabolites from the most active extract. Analgesic
      activities of all extracts and subextracts at the doses of 5, 10 and 30 mg/kg
      (i.p.) were examined using hot plate test in mice. Among the tested extracts,
      MeOH extract prepared from the aerial parts and the n-butanol subextract prepared
      thereof displayed the best analgesic activity at all doses. Phytochemical studies
      on n-butanol subextract led to the isolation of two new iridoid glycosides as an
      inseparable mixture, 8-O-acetyl-4'-O-(E)-(p-coumaroyl)-harpagide (1) and 8-O
      acetyl-4'-O-(Z)-(p-coumaroyl)-harpagide (2) along with five known secondary
      metabolites, beta-sitosterol 3-O-beta-glucopyranoside (3), apigenin 7-O-beta
      glucopyranoside (4), apigenin 7-O-rutinoside (5), luteolin 7-O-beta
      glucopyranoside (6) and luteolin 7-O-rutinoside (7). The iridoid mixture (1 and
      2), 3 and 4 elicited significant inhibition of pain at 5 mg/kg dose.

PMID- 28758427
TI  - Genome-wide DNA methylation profiling of the regenerative MRL/MpJ mouse and two
      normal strains.
AB  - AIM: We aimed to identify the pivotal differences in the DNA methylation profiles
      between the regeneration capable MRL/MpJ mouse and reference mouse strains.
      MATERIALS & METHODS: Global DNA methylation profiling was performed in ear
      pinnae, bone marrow, spleen, liver and heart from uninjured adult females of the
      MRL/MpJ and C57BL/6J and BALB/c. RESULTS & CONCLUSION: A number of differentially
      methylated regions (DMRs) distinguishing between the MRL/MpJ mouse and both
      references were identified. In the ear pinnae, the DMRs were enriched in genes
      associated with development, inflammation and apoptosis, and in binding sites of
      transcriptional modulator Smad1. Several DMRs overlapped previously mapped
      quantitative trait loci of regenerative capability. The results suggest potential
      epigenetic determinants of regenerative phenomenon.

PMID- 28758428
TI  - The Proteins from Sika deer antler as potential modulators on cisplatin-induced
      cytotoxicity in human embryonic kidney 293 cells.
AB  - Our study aimed to investigate the protective role of SDAPR on cisplatin-induced
      cytotoxicity and its' possible mechanism in HEK293 cells. Cell viability was
      measured by MTT assay. Oxidative stress (SOD, GSH, LDH and MDA), inflammatory
      factors (TNF-alpha and IL-6) and apoptosis-related proteins (caspase-3, Bax, Bcl
      2) expression were measured. The apoptotic cells were observed by TUNEL staining.
      Our study results indicated that non-cytotoxic levels of SDAPR significantly
      increased viability rate (LD50 value of cisplatin is 20 MUM), which improved
      antioxidant defence, attenuated apoptosis by decreasing expression levels of
      cleaved-caspase-3 and Bax, increasing Bcl-2 expression and inhibiting apoptotic
      positive cells in HEK 293 cells. In addition, SDAPR treatment markedly inhibited
      the levels of TNF-alpha and IL-6. In conclusion, Sika deer antler protein, a
      potential modulator, could alleviate cisplatin-induced cytotoxicity in HEK 293
      cells.

PMID- 28758429
TI  - A Rare Complication of Campylobacter Sepsis in an Infant.

PMID- 28758430
TI  - Calpain inhibitor I attenuates atherosclerosis and inflammation in
      atherosclerotic rats through eNOS/NO/NF-kappaB pathway.
AB  - We previously reported that calpain, the Ca2+-sensitive cysteine protease, gets
      involved in atherogenesis. This study aimed to investigate the effects of calpain
      inhibitor I (CAI, 5 mg/kg per day) with or without NG-nitro-l-arginine-methyl
      ester (l-NAME) (100 mg/kg per day), the inhibitor of nitric oxide synthase (NOS),
      on atherosclerosis and inflammation in a rat model induced by high-cholesterol
      diet (HCD). The results demonstrated HCD increased protein expression of calpain
      1 but not calpain-2 in aortic tissue. In addition, CAI reduced the thickness of
      atherosclerotic intima compared with HCD group, which was weakened by the l-NAME
      combination. CAI with or without l-NAME decreased the activity of calpain in the
      aorta. Also, CAI decreased the expressions of vascular cell adhesion molecule-1
      (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), and monocyte
      chemoattractant protein-1 (MCP-1) in the aorta at the levels of both mRNA and
      protein. Furthermore, CAI increased the activity and the protein expression of
      endothelial NOS (eNOS) accompanied by increased content of NO and downregulated
      the protein expression of nuclear factor kappaB (NF-kappaB) of the nucleus in the
      aorta. However, the abovementioned effects were at least partly cancelled by l
      NAME except for the protein expression of eNOS. The results suggested that CAI
      attenuated atherosclerosis and inflammation through eNOS/NO/NF-kappaB pathway.

PMID- 28758431
TI  - PRODIGE: PRediction models in prOstate cancer for personalized meDIcine
      challenGE.
AB  - AIM: Identifying the best care for a patient can be extremely challenging. To
      support the creation of multifactorial Decision Support Systems (DSSs), we
      propose an Umbrella Protocol, focusing on prostate cancer. MATERIALS & METHODS:
      The PRODIGE project consisted of a workflow for standardizing data, and
      procedures, to create a consistent dataset useful to elaborate DSSs. Techniques
      from classical statistics and machine learning will be adopted. The general
      protocol accepted by our Ethical Committee can be downloaded from cancerdata.org
      . RESULTS: A standardized knowledge sharing process has been implemented by using
      a semi-formal ontology for the representation of relevant clinical variables.
      CONCLUSION: The development of DSSs, based on standardized knowledge, could be a
      tool to achieve a personalized decision-making.

PMID- 28758432
TI  - Psychotropic medication use in Australia, 2007 to 2015: Changes in annual
      incidence, prevalence and treatment exposure.
AB  - OBJECTIVE: To examine changes in annual patterns of psychotropic medication use
      in Australia from 2007 to 2015. METHODS: We used a 10% sample of individual-level
      nationwide dispensing claims for concessional beneficiaries dispensed
      psychotropic medications (stratified by class, subclass) to investigate annual
      trends and changes in the incidence and prevalence of use, median annual duration
      of exposure, proportion of people with single psychotropic dispensing and median
      defined daily doses per person dispensed each medicine per year. RESULTS: Over
      the study period, there was a 26.1% decrease in the incidence and a 2.6% increase
      in the prevalence of all psychotropic medicine use. We observed a decrease in the
      annual incidence and prevalence of antidepressants (11.6% and 16.8%,
      respectively) but increases in the median annual duration of exposure (7.4%).
      Amitriptyline had the highest proportion of single dispensings of all
      antidepressants throughout the study period (26.5% in 2015) and defined daily
      doses per person dispensed each medicine per year increased by 20% for
      antidepressants overall. Benzodiazepine use decreased across all measures over
      the study period apart from long-term use (exposure for >240 days of the year),
      which in 2015 was 23.6% of those dispensed a benzodiazepine. We observed a
      relative increase in the incidence and prevalence of antipsychotic use (14.2% and
      26.8%, respectively), and haloperidol had the highest proportion of single
      dispensings of any antipsychotic throughout the study period (47.5% in 2015). We
      observed a relative increase in the incidence and prevalence of attention-deficit
      hyperactivity disorder medication use of 114.0% and 101.8%, respectively, over
      the study period. CONCLUSION: Increasing doses and treatment durations of
      antidepressants warrants further investigation due to concerns about overuse.
      Single dispensings of amitriptyline and haloperidol may indicate off-label use
      and long-term use of benzodiazepines remains problematic. Despite increases in
      attention-deficit hyperactivity disorder medication use, prevalence of use is
      still much lower than the estimated prevalence of attention-deficit hyperactivity
      disorder in the adult population.

PMID- 28758433
TI  - [The importance of Bladder Contractility Index in the management of underactive
      bladder].
AB  - AIM: To evaluate the importance of BCI in the management of underactive bladder
      (UB). MATERIAL AND METHOD: A retrospective study over a period of 3 years and 9
      months (January 2013-September 2016) in Mures County Hospital, Clinic of Urology,
      including 91 patients. Detrusor underactivity was defined by BCI less than 100
      using the formula: PdetQmax+5Qmax. RESULTS: The median of Qmax value was 7 ml/s
      and the median value of Pdet was 14 cm H2O. The median value of BCI was 55 with
      extremities between 17 and 110. BCI tends to decrease with age and there is a
      relation between value of BCI and diabetes (p = 0,003) and neurological diseases
      (p = 0,015). CONCLUSIONS: The UB diagnosis represents a real challenge for the
      urologist, so that, urodynamical findings such as absence of bladder obstruction,
      post-void residual urine, Qmax, together with BCI value, helps in setting the
      proper management. Orv Hetil. 2017; 158(31): 1222-1227.

PMID- 28758434
TI  - [Human papillomavirus associated cervix uteri morbidity in Hungary: epidemiology
      and correlation with the HPV types and the simultaneous cytological diagnosis].
AB  - INTRODUCTION: Persistent infection of human papillomavirus is known to cause
      cervical intraepithelial neoplasia or cancer in the cervix uteri and other HPV
      associated cancers in different localization. Based on epidemiological and
      biological data, principally the high risk HPV is responsible for development of
      cervical these cancers. However, we have no information about the frequently
      distribution of different HPV types and what is the correlation between the HPV
      types and cytological diagnosis in cervical intraepithelial neoplasia (CIN). AIM:
      In this paper, we are going to present new data involving incidence and mortality
      of HPV-associated cancers during the period of 2009-2015 in Hungary. We are also
      going to investigate the correlation of cervical cytological diagnosis and HPV
      typing, and the preventive effect of HPV vaccination. METHOD: The epidemiological
      data spring from the National Cancer Registry. HPV typing was performed by Linear
      Array HPV Genotyping Test. Simultaneous cytological diagnosis and HPV typing was
      carried out on 2048 cytological samples collected in period of 2009-2016.
      RESULTS: According to the epidemiologic data, the most frequently occurring HPV
      associated cancer is the laryngeal carcinoma in man, and the cervical cancer in
      woman in Hungary. During the 2009-2015 time intervals, the frequency distribution
      of head and neck cancers was not changed in man, but the incidence of tongue root
      squamous cell carcinomas was gradually increasing in woman. We have defined the
      clinical significance of single and simultaneously multiple HPV infection and
      have investigated the correlation of the HPV frequency distribution and
      cytological diagnosis in CIN. It was found that in the cytological negativity of
      probably/possibly carcinogen pHR-HPV group classified by IACR was much more
      frequent as in HR-HPV group (56% versus 47%). The presence of simultaneous
      multiplex HPV infection betokens an increased cancer risk. According to the
      international publications, the ratio of HPV16 just twice as big as in cervical
      cancer, what we found in CIN (60% versus 30%). The frequency order of the HPV18
      is 2nd in cancer, and 9th in CIN. Comparing the frequency distribution of HR/pHR
      HPVs in cervical cancer and CIN, the HR-HPV35 is very rarely occurring in CIN,
      the pHR-HPV56, 66, and 73 is more frequently seen in CIN as in carcinoma.
      Appreciated the preventive value of anti-HPV vaccines, we have found a
      significant differences in group with 1 HPV/sample and in group with more than 1
      HPV/sample. CONCLUSION: The frequency distribution of tongue root squamous cell
      carcinoma and cervical cancer was gradually increasing in woman. The overall
      preventive effect of 9-valent vaccine is 80.3%. This preventive value should be
      higher because of the transformation ability of the different HPV types is not
      same. Out of consideration for HPV incidence in cancer, the preventive effect of
      9-valent or 4-valent vaccines might reach to 93% or 73%. However, the pHR-HPVs
      are biologically active, it is not sufficient for the inclusion of these HPV
      types into population-wide HPV-DNA based cervical screening programs. Orv Hetil.
      2017; 158(31): 1213-1221.

PMID- 28758435
TI  - [Treating tissue defects following tooth removal. Three case reports].
AB  - Following tooth removal, three dimensional hard- and soft-tissue loss take place.
      Spontaneous healing makes the defect more severe and results in collapsing
      tissues. Implant placement is not feasible. In the aestethic zone even fixed
      partial dentures will not deliver the expected result. Our aim was to demonstrate
      that only ridge preservation enables implant placement and also provides
      excellent aestetic result even at frontal areas. CBCT was made before and 6-8
      months after ridge preservation. Vertical and socket area measurements were
      carried out and compared in pre-, and postoperative images. Implant placement was
      feasible in all three cases; furthermore favourable buccal bone (4.24 mm, 6.22
      mm, 9.57 mm) and area growth (129%, 145%, 167%) were measured. Ridge preservation
      provides appropriate therapy for complete reconstruction of tissues after tooth
      removal. Orv Hetil. 2017; 158(31): 1228-1234.

PMID- 28758436
TI  - [Diagnostics and treatment of infectious keratitis].
AB  - We summarize up-to-date diagnostic and treatment of infectious keratitis using
      literature data and some clinical examples. In the clinical practice, most
      commonly bacterial, herpetic, mycotic and acanthamoeba keratitis occur. Beside
      slitlamp examination, for diagnostic purpose, we analyse corneal sensitivity,
      perform in vivo confocal microscopy, polymerase-chain-reaction (PCR), in vitro
      culture and histological examination of the corneal sample. As conservative
      treatment we use primarily topical moxifloxacin or cephasolin with fortified
      tobramycin or gentamycin in bacterial, topical antiviral gel (in some cases in
      combination with systemic antiviral treatment) in part in combination with
      topical corticosteroids in herpetic, voriconasole or amphotericin-B in mycotic,
      and topical-triple-therapy (diamidine, biguanid and antibiotics) in acanthamoeba
      keratitis. In case of early diagnosis and initiation of topical therapy, most
      cases of infectious keratitis recover successfully. However, beside conservative
      treatment, penetrating keratoplasty, amniotic membrane transplantation and
      crosslinking therapy may be necessary. Crosslinking is solely contraindicated in
      herpetic keratitis. Orv Hetil. 2017; 158(31): 1203-1212.

PMID- 28758438
TI  - Energy Balance-Related Behavior and Anthropometric Measures Among Adolescents
      Across Three Educational Levels: A Cross-Sectional Study in Dutch Schools.
AB  - Energy balance-related behavior on schooldays and beliefs about school-based
      interventions may differ between students in different educational levels, sexes,
      and BMI (body mass index) categories. In Zwolle (the Netherlands), 1,084
      adolescents (13-15 years) at 9 secondary schools completed a questionnaire.
      Overweight prevalence (boys 18.1%, girls 19.3%) increased with decreasing
      educational level, especially in boys. Girls reported healthier behavior than
      boys regarding daily consumption of fruit (35% vs. 29%), vegetables (58% vs.
      48%), <=1 snack/candy (36% vs. 26%), <=3 glasses of sugared drinks (80% vs. 73%;
      all p < .05). Unhealthier dietary behaviors were associated with lower
      educational level, except for eating sugary and savory snacks. Snacks and sugared
      drinks consumed at school were mostly brought from home (61.6% and 68.5%,
      respectively). Overweight students reported less frequent consumption of daily
      breakfast, snacks, and sugared drinks than nonoverweight students. Of all
      students, 40% spent >=1 hour per day cycling to school. Lower educational level
      students reported less organized sports activities than higher level students,
      but more outside play and other activities. Overweight was associated with
      cycling to school (boys) and participating in organized sports (girls). More
      girls than boys were interested in lessons about healthy nutrition (44.4% vs.
      31.7%). To stimulate physical activity, boys suggested more physical education
      classes (63%), girls advised more variation (47%) and choice (43%). A healthy
      school canteen (57%) and offering free fruit (67%) were suggested as promising
      interventions to stimulate healthy behavior. Educational and environmental
      interventions to tackle unhealthy dietary and physical activity behavior should
      be developed in collaboration with parents and tailored to educational level and
      gender.

PMID- 28758439
TI  - Pathoanatomy and Associated Injuries of Posterior Malleolus Fracture of the
      Ankle.
AB  - BACKGROUND: We present a classification system that progresses in severity,
      indicates the pathomechanics that cause the fracture and therefore guides the
      surgeon to what fixation will be necessary by which approach. METHODS: The
      primary posterior malleolar fracture fragments were characterized into 3 groups.
      A type 1 fracture was described as a small extra-articular posterior malleolar
      primary fragment. Type 2 fractures consisted of a primary fragment of the
      posterolateral triangle of the tibia (Volkmann area). A type 3 primary fragment
      was characterized by a coronal plane fracture line involving the whole posterior
      plafond. RESULTS: In type 1 fractures, the syndesmosis was disrupted in 100% of
      cases, although a proportion only involved the posterior syndesmosis. In type 2
      posterior malleolar fractures, there was a variable medial injury with mixed
      avulsion/impaction etiology. In type 3 posterior malleolar fractures, most
      fibular fractures were either a high fracture or a long oblique fracture in the
      same fracture alignment as the posterior shear tibia fragment. Most medial
      injuries were Y-type or posterior oblique fractures. This fracture pattern had a
      low incidence of syndesmotic injury. CONCLUSION: The value of this approach was
      that by following the pathomechanism through the ankle, it demonstrated which
      other structures were likely to be damaged by the path of the kinetic energy.
      With an understanding of the pattern of associated injuries for each category, a
      surgeon may be able to avoid some pitfalls in treatment of these injuries. LEVEL
      OF EVIDENCE: Level III, retrospective comparative series.

PMID- 28758441
TI  - Beware Predatory Journals.

PMID- 28758443
TI  - Letter Regarding: Anterior Heterotopic Ossification at the Talar Neck After Total
      Ankle Arthroplasty.

PMID- 28758444
TI  - Response to "Letter Regarding: Anterior Heterotopic Ossification at the Talar
      Neck After Total Ankle Arthroplasty".

PMID- 28758445
TI  - Amy Gatehouse, Health Information Coordinator.

PMID- 28758448
TI  - Australian Mortality Coding: History, Benefits and Future Directions.

PMID- 28758447
TI  - Team-Based Approaches to Health Informatics Research.

PMID- 28758446
TI  - Angela Boal, Senior Program Manager.

PMID- 28758449
TI  - Ninth Annual Electronic Health and EH Records Congress Sydney 5-6 June 2006.

PMID- 28758451
TI  - The Professional Journal.

PMID- 28758450
TI  - Coding Audits - A Positive Experience.

PMID- 28758453
TI  - President's Report: Health Informatics.

PMID- 28758452
TI  - Angela Bayley, Senior Data Manager.

PMID- 28758454
TI  - Still Work to Do on Standards.

PMID- 28758456
TI  - President's Report.

PMID- 28758455
TI  - e-Health Conference Sydney 30-31 October 2006.

PMID- 28758457
TI  - Three Nights in Beijing: An Australian's Perspective of the First Annual Summit
      on Healthcare Informatics Asia Pacific, Beijing, the People's Republic of China,
      19-20 April 2006.

PMID- 28758458
TI  - Developing an Allied Health Code Set: The Indicator for Intervention.

PMID- 28758459
TI  - Classifications and Terminologies.

PMID- 28758460
TI  - Editorial.

PMID- 28758462
TI  - Melissa Suares, Clinical Data Coordinator and Applications Researcher.

PMID- 28758463
TI  - Australian Institute of Health Policy Studies (AIHPS) Conference: e-Health:
      Transforming the Healthcare Landscape. Melbourne July 2006.

PMID- 28758464
TI  - President's Report.

PMID- 28758465
TI  - Editorial.

PMID- 28758466
TI  - Provisional Coding Practices: Are They Really a Waste of Time?
AB  - In order to facilitate effective clinical coding and hence the precise financial
      reimbursement of acute services, in 2005 Western District Health Service (WDHS)
      (located in regional Victoria, Australia) undertook a provisional coding trial
      for inpatient medical episodes to determine the magnitude and accuracy of
      clinical documentation. Utilising clinical coding software installed on a laptop
      computer, provisional coding was undertaken for all current overnight inpatient
      episodes under each physician one day prior to attending their daily ward round.
      The provisionally coded episodes were re-coded upon the completion of the
      discharge summary and the final Diagnostic Related Group (DRG) allocation and
      weight were compared to the provisional DRG assignment. A total of 54 out of 220
      inpatient medical episodes were provisionally coded. This represented
      approximately a 25% cross section of the population selected for observation.
      Approximately 67.6% of the provisionally allocated DRGs were accurate in contrast
      to 32.4% which were subject to change once the discharge summary was completed.
      The DRG changes were primarily due to: disease progression of a patient during
      their care episode which could not be identified by clinical coding staff due to
      discharge prior to the following scheduled ward round; the discharge destination
      of particular patients; and the accuracy of clinical documentation on the
      discharge summary. The information gathered from the provisional coding trial
      supported the hypothesis that clinical documentation standards were sufficient
      and adequate to support precise clinical coding and DRG assignment at WDHS. The
      trial further highlighted the importance of a complete and accurate discharge
      summary available during the coding process of acute inpatient episodes.

PMID- 28758467
TI  - Health Information Service Management.

PMID- 28758469
TI  - Elvis Maio, Project Officer.

PMID- 28758468
TI  - Rogers v Whitaker: Still Crazy after all These Years?

PMID- 28758470
TI  - Medinfo 2007 Congress: Building Sustainable Health Systems. Twelfth World
      Congress on Health (Medical) Informatics 20-24 August 2007, Brisbane, Australia.

PMID- 28758471
TI  - Health Information Management in Australia: A Brief History of the Profession and
      the Association.

PMID- 28758472
TI  - Duty of Confidentiality and HIV/AIDS.
AB  - The duty to maintain patient confidentiality is an ethical and legal priority for
      all health professionals. There is a common law duty in addition to statutory
      duties imposed by various privacy statutes. An ethical dilemma can arise when a
      patient is diagnosed with HIV/AIDS because a practitioner becomes aware that
      third parties can be placed at risk of a serious infection if the patient passes
      the disease on to those parties. The question arises as to what extent a medical
      practitioner, should he or she suspect a patient to be a risk of being HIV
      positive, is legally and ethically obliged to counsel the patient to undergo HIV
      antibody testing. In a case heard in the New South Wales Supreme Court in 1999,
      BT v Oei (1999) NSWSC 1082, a medical practitioner was held to owe a duty of care
      to the sexual partner/s of a patient whom he should have counselled to have HIV
      testing, who in fact tested positive after a period of time and had in turn
      infected his wife.

PMID- 28758473
TI  - President's Report.

PMID- 28758474
TI  - Coronial Services Centre Open Day, Thursday 3 August 2006.

PMID- 28758475
TI  - Health Metrics Network and Mortality Data.

PMID- 28758477
TI  - The National Coroners Information System: Contributing to Death and Injury
      Prevention.

PMID- 28758476
TI  - Privacy and Personal Information Protection: A Judicial Interpretation of a
      Legislative Response in NSW.

PMID- 28758478
TI  - Editorial: When Did We Start Doing That? Documenting the Evolution of Health
      Information in Australia.

PMID- 28758479
TI  - Editorial Mortality Records: The Silent Witness.

PMID- 28758480
TI  - A Response to Daking and Dodds.

PMID- 28758481
TI  - Editorial: The Global Nature of Health Information Management and Systems.

PMID- 28758482
TI  - Odette Taylor: Health Information Manager, Victorian Perinatal Data Collection
      Unit, Department of Human Services.

PMID- 28758484
TI  - The HIMAA Professional Credentialling Scheme.

PMID- 28758483
TI  - Tammy Corica: Study Coordinator, Department of Radiation Oncology, Sir Charles
      Gairdner Hospital, Western Australia.

PMID- 28758485
TI  - Fifty Years as a Health Information Management Professional: An American
      Perspective.

PMID- 28758486
TI  - Alison Bidie: Program Consultant, Data Quality, Canadian Institute for Health
      Information, Toronto, Canada.

PMID- 28758487
TI  - Outpatient Correspondence - Boiled Lollies to Chocolates.

PMID- 28758488
TI  - Litigation and Doctor-Patient Confidentiality.
AB  - When a patient sues a healthcare practitioner with regard to their care, the
      healthcare records are an important part of the evidence used in the case.
      Litigation is usually heard in open court in the presence of the public and
      information contained within the records can be aired in that public forum. The
      issue of patient confidentiality and litigation arose in the case of Kadian v
      Richards [2004] NSWSC 382, which forms the basis for this report. The decision in
      Kadian preserves the right of patients to confidentiality of their medical
      records other than when a patient sues a practitioner for negligence in the
      delivery of health care; the loss of confidentiality is limited to what is
      necessary to enable the defendant doctor to prepare an adequate defence; and
      patient-doctor confidentiality with subsequent treating doctors is preserved
      unless it becomes inconsistent for the plaintiff patient to press on with
      litigation while continuing to maintain a full obligation of confidentiality with
      those doctors.

PMID- 28758491
TI  - Halina Hili: From Health Information Manager to Quality Manager.

PMID- 28758490
TI  - President's Report: Health Information Management and Epidemiological Research.

PMID- 28758493
TI  - Leilei Zhu: Clinical Classification Consultant.

PMID- 28758492
TI  - Case Study - Classification: Developing a Model for an Iranian Classification of
      Diseases (IRCD) Compatible with other Adaptations of the International
      Classification of Diseases (ICD).
AB  - The introduction of the electronic health record in Iran has necessitated the
      development of a model for an Iranian Classification of Diseases (IRCD) which is
      compatible with classifications used in other countries. This article reports on
      a comparative study of the adaptations of the International Classification of
      Diseases (ICD) currently in use in the USA, France, Germany, China and Egypt
      which was carried out in order to inform development of the IRCD. Data concerning
      the history, evolutionary processes and general structures of tabular lists,
      alphabetic lists and manuals of World Health Organization (WHO) classifications
      were collected during the period 2003-2004 from a variety of sources including
      written texts, periodicals, the Internet and electronic mail. Based on this
      information, and following assessment by 17 Iranian national experts by means of
      a questionnaire, a model of IRCD compatible with versions of the ICD used in
      other countries, in particular with that of USA, was proposed.

PMID- 28758494
TI  - The Centre for Health Record Linkage: A New Resource for Health Services Research
      and Evaluation.

PMID- 28758495
TI  - Letter to the Editor.

PMID- 28758496
TI  - Keeping Our Classification UP to Date.
AB  - In Australia, the National Centre for Classification in Health (NCCH) is
      ultimately responsible for updating ICD-10-AM disease codes and Australian
      Classification of Health Interventions (ACHI) procedure codes, and the
      accompanying Australian Coding Standards (ACS). New editions of these
      publications are released every two years. This article outlines the updating
      procedure and lists the sources of information upon which the NCCH draws when
      compiling data for new coding manuals.

PMID- 28758498
TI  - NEHTA's Role in Australia's e-health Reform: An Update of Work to Date.

PMID- 28758497
TI  - Tavia Rudd: Health Information Management Services Manager, Langley Porter
      Hospital and Clinics, University of California, San Francisco.

PMID- 28758499
TI  - Mortality Data in the Kingdom of Tonga: A Review of Changing Trends over the Ten
      Years since 1996.

PMID- 28758500
TI  - Fifteenth Congress of the International Federation of Health Records
      Organizations (IFHRO). Seoul, South Korea 28-31 May 2007.

PMID- 28758501
TI  - Australian Hospital Data: Not Just for Funding.
AB  - Collections of routine, or 'administrative', hospital data have many applications
      in health care and are now recognised as valuable sources of information. In
      recent decades, administrative data have been seen primarily as funding and
      billing tools to assist with the reimbursement of hospitals for services
      provided; this purpose remains the primary focus of the clinical coder workforce.
      More recently, hospital data have been recognised as valuable resources for a
      range of health system improvement processes beyond funding. The focus of this
      paper is to review and demonstrate the diverse uses of administrative data in
      health services research and quality improvement. By gaining an understanding of
      how the data are used, we can appreciate the importance of good quality data from
      the perspective of its multiple uses. This paper describes a sample of the
      studies conducted in Australia using administrative data in health care
      improvement.

PMID- 28758503
TI  - Defending metropolitan identity through colonial politics: The role of Portuguese
      naturalists (1870-91).
AB  - This paper explores how Joao de Andrade Corvo and Jose Vicente Barbosa du Bocage,
      two nineteenth-century Portuguese naturalists, were able to reach prominent
      political positions in their country by means of their work in, respectively,
      botany and agriculture, and zoology. The authority they derived from their
      scientific activities and the knowledge they acquired in the process, favored by
      their proximity to particular political quarters, elevated them to important
      governmental offices, in the context of which they implemented policies that
      reinforced Portugal's identity as an imperial nation. The colonial policies and
      agreements signed by Corvo and Bocage aimed at securing Portuguese colonial
      territories, which, aside from their economic relevance, constituted a symbol of
      power that reinforced the sovereignty of a small nation in a Europe dominated by
      the rule of increasingly vaster and stronger states. In spite of their different
      scientific careers and personal interests, both naturalists played key roles in
      Portuguese foreign affairs and colonial negotiations of the late nineteenth
      century, especially during the Scramble for Africa.

PMID- 28758502
TI  - Unexpected effect of urate on hydrogen peroxide-induced oxidative damage in
      embryonic chicken cardiac cells.
AB  - Uric acid (UA) is a potent scavenger of oxidants in most mammalian and avian
      species. The aim of this study was to obtain more comprehensive information
      regarding the relationship between different concentrations of UA and oxidative
      balance in chicken cardiac cells. First, oxidative damage parameters were
      measured in chicken cardiac cells treated with different concentrations of UA. UA
      concentrations within the normal physiological range had no effect, while
      treatment with a high level of UA, i.e. 1200 MUM, increased the malondialdehyde
      (MDA) and protein carbonyl contents, decreased the superoxide dismutase (SOD) and
      catalase (CAT) activities, and had no effect on glutathione (GSH) in cardiac
      muscle cells. In addition, the nuclear factor erythroid 2-related factor 2 (Nrf2)
      pathway was stimulated in cells treated with 1200 MUM UA. Next, the role of UA in
      protecting cells from oxidative damage was investigated in hydrogen peroxide
      (H2O2)-damaged chicken cardiac cells. Treatment with UA within the normal
      physiological range reduced the increased MDA and protein carbonyl contents and
      SOD enzymatic activity induced by H2O2 exposure to some extent and inhibited
      reactive oxygen species (ROS) formation, presumably as a result of the Nrf2
      pathway activation in H2O2-damaged cells. By contrast, the MDA and protein
      carbonyl contents were increased, SOD enzymatic activity was depressed, and the
      Nrf2 pathway was further down-regulated in H2O2-damaged cells treated with 1200
      MUM UA. In conclusion, the results indicated that physiological UA concentration
      partially alleviated oxidative stress in chicken cardiac muscle cells treated
      with H2O2. However, supraphysiological UA concentrations promoted oxidative
      damages directly in primary cultured chicken cardiac muscle cells and aggravated
      oxidative stress in H2O2-damaged cells.

PMID- 28758504
TI  - Investigational drugs in systemic vasculitis.
AB  - INTRODUCTION: Treatment of systemic vasculitis is based on glucocorticoids (GC)
      in association with immunosuppressive therapy. There are still unmet needs,
      including earlier onset of response, more targeted therapies, reduction of
      relapse-risk and decrease of long-term GC and classic immunosuppressants
      toxicities. Areas covered: In this review, we discuss investigational drugs in
      early phase clinical trials for induction of remission in vasculitis. We focus on
      ANCA-associated vasculitis, Behcet's disease, giant cell arteritis, Takayasu
      arteritis, and cryoglobulinemic vasculitis. We performed a comprehensive review
      of articles published on pubmed and a review of clinical trials registered online
      ( https://clinicaltrials.gov ) for each vasculitis. Expert opinion: Recent
      progress in the pathogenesis identifies new therapeutic targets. Some of these
      therapies are promising in GC sparing effects, in reducing relapse rate, and for
      their safety profile. These results need to be confirmed in large-scale phase III
      studies.

PMID- 28758505
TI  - Rehabilitation and Disability Services' Quality Projects: A Comparison against
      the Australian Council on Healthcare Standards' Clinical Criteria.
AB  - The Australian Council on Healthcare Standards (ACHS) Evaluation, Quality and
      Improvement (EQuIP 4)1 standards provide a useful clinical and corporate
      framework for the analysis of quality projects by both health and disability
      services. Two ACHS EQuIP 4 clinical standards were used to compare quality
      projects conducted by community-based and on-site rehabilitation and disability
      services, as generated by a commercial database. Reliable information is a major
      asset for healthcare organisations, and the use of the ACHS clinical standards to
      interpret quality project data can overcome a lack of conceptual framework to
      interpret data. Key differences in the types of quality projects entered in the
      database by the rehabilitation and disability services may be attributed to the
      rehabilitation services' relationship with the client (patient), which is time
      limited according to the clients' rehabilitation progress, while in comparison,
      disability services provide life-long support.

PMID- 28758506
TI  - Exposure to modern, widespread environmental endocrine disrupting chemicals and
      their effect on the reproductive potential of women: an overview of current
      epidemiological evidence.
AB  - Growing evidence indicates that exposure to widespread, environmental
      contaminants called endocrine disruptors (EDCs) negatively affects animal and
      human reproductive health and has been linked to several diseases including
      infertility. This review aims to evaluate the impact of environmental exposure to
      endocrine disrupting chemicals [phthalates, parabens, triclosan, bisphenol A
      (BPA), organochlorine (PCBs) and perfluorinated (PFCs) compounds] on the
      reproductive potential among women, by reviewing most recently published
      literature. Epidemiological studies focusing on EDCs exposure and reproductive
      potential among women for the last 16 years were identified by a search of the
      PUBMED, MEDLINE, EBSCO and TOXNET literature databases. The results of the
      presented studies show that exposure to EDCs impacts the reproductive potential
      in women, measured by ovarian reserve and by assisted reproductive technology
      outcomes. Exposure to environmental endocrine disrupting chemicals decrease: (i)
      oestradiol levels (BPA); (ii) anti-Mullerian hormone concentrations (PCBs); (iii)
      antral follicle count (BPA, parabens, phthalates); (iv) oocyte quality (BPA,
      triclosan, phthalates, PCBs); (v) fertilization rate (PFCs, PCBs); (vi)
      implantation (BPA, phthalates, PCBs); (vii) embryo quality (triclosan, PCBs,
      BPA); (viii) rate of clinical pregnancy and live births (parabens, phthalates).
      The studies were mostly well-designed and used prospective cohorts with the
      exposure assessment based on the biomarker of exposure. Considering the suggested
      health effects, more epidemiological data is urgently needed to confirm the
      presented findings.

PMID- 28758507
TI  - Changes in Behaviors and Outcomes Among School-Based Employees in a Wellness
      Program.
AB  - OBJECTIVE: To examine the health behavior changes and mental-health and job
      related outcomes of school-based employees over 2 years while participating in a
      worksite wellness program. METHOD: All participants in this analysis (n = 1,873)
      were employees of a large public school district in the western United States and
      voluntarily enrolled in a comprehensive wellness program. Exercise level, fruit
      and vegetable consumption, restful sleep, smoking, alcohol consumption, self
      rated health, mental health-related outcomes (stress, depression, life
      satisfaction, and loneliness), and job-related outcomes (job performance,
      absenteeism, job-related satisfaction) are reported. RESULTS: There was an
      increase in days and minutes/week exercised, fruit/vegetable consumption, days
      per week of restful sleep, and a decrease in alcohol consumption (ps < .037) over
      2 years. Among those who reported smoking, the number of days smoked increased
      after 1 year but then dropped below baseline levels at year 2 (p < .0001).
      Several mental health-related outcomes improved (ps < .033); however, job
      performance was slightly lower (? 2%), and the other job-related outcomes were
      unchanged. CONCLUSION: School employees may benefit from a comprehensive worksite
      wellness program, particularly to improve health behaviors. However, mental
      health and job-related outcome results were mixed over 2 years.

PMID- 28758508
TI  - Health Information Manager, Warringal Private Hospital, Melbourne: Profile of a
      Coder.

PMID- 28758509
TI  - Polycystic Ovary Syndrome among Obese Adolescents.
AB  - BACKGROUND AND AIMS: In adolescence and obesity, the pathophysiology of
      polycystic ovary syndrome (PCOS) is very difficult to distinguish. We aimed to
      assess the diagnosis of PCOS in the population of obese adolescent. METHODS:
      Cross-sectional study. SETTING: Pediatric Endocrinology Weight and Management
      Clinic from Children's Institute, Sao Paulo, Brazil. PARTICIPANTS: Forty-nine
      post-menarcheal obese adolescents with mean age of 14.7 years. INTERVENTIONS:
      Anthropometric assessment and review of medical records were done. Clinical and
      laboratory hyperandrogenism were quantified using Ferriman-Gallwey index and
      androgenic dosages, respectively. Ovarian morphology was evaluated through
      suprapubic ultrasonography. RESULTS: By the 2015 Witchel et al. guideline for
      PCOS in adolescence, 18.4% were diagnosed as having PCOS. When assessed by
      Rotterdam, Androgen Excess and PCOS Society, and American National Institute of
      Health criteria's, 26.4%, 22.4%, and 20.4% had PCOS, respectively. Irregular
      menstrual cycles were found in 65.3% of patients. Clinical hyperandrogenism was
      observed in 16.3% of girls and 18.4% had elevated serum androgen values.
      Suprapubic ultrasonography revealed enlarged ovaries in 18.4% of the adolescents.
      CONCLUSIONS: PCOS in all-comers obese adolescents from a Weight and Management
      Clinic in a quaternary hospital is more frequent when compared to adult women
      showed in the literature.

PMID- 28758511
TI  - Health Classification - A Complex World.

PMID- 28758510
TI  - The Impact of ICT on Healthcare and on Health Information Management.

PMID- 28758512
TI  - 'Sailing the Seven Cs' with the Clinical Coders' Creed. The Eighth 'C': Private
      Sector Coding.
AB  - This article briefly relates the experience of a clinical coder working in the
      private healthcare sector in the Australian state of New South Wales and
      questions whether it is possible to work in this environment while adhering to
      the Clinical Coders' Creed. Private facilities in Australia that handle acute,
      psychiatric, respite and rehabilitation cases, rely mainly upon health insurance
      funds for reimbursement for episodes of care, which are funded according to DRGs
      based on codes assigned by clinical coders. The point is made that while all
      coders strive to fully and accurately describe the clinical episode of care
      regardless of healthcare setting, a distinction can be drawn between public and
      private sector coding in relation to financial contracts, which form the basis of
      private health care. Therefore, it is recommended that private sector coders
      familiarise themselves with this "C" as well as the other seven "Cs" of the
      Clinical Coders' Creed.

PMID- 28758513
TI  - Aspects of Coding in Canada: Through the Eyes of an Australian HIM.
AB  - For the purpose of this brief update report, the author (an Australian Health
      Information Manager currently working in Canada) was asked to select certain
      aspects of the current coding system in Canada that she believes highlight
      relevant differences between the Canadian and Australian systems, on the
      assumption that this might be of interest to other Australian HIMs. The author
      has provided a brief overview of some recent changes to the Canadian
      classification system (e.g. new electronic product replacing coding books), as
      well a focus on some aspects of coder training and coding studies as seen through
      the eyes of an Australian HIM.

PMID- 28758514
TI  - The Coding Conundrum: A Workplace Perspective.
AB  - Over the last few decades clinical coding has grown in complexity and importance
      in the eyes of bureaucrats, administrators and clinicians, as new uses for this
      valuable resource are constantly being identified. Anecdotal evidence suggests
      that many Australian hospitals are currently experiencing difficulty in both
      recruiting and retaining clinical coders. The current shortage of clinical coders
      is a national problem, rather than being peculiar to any one state, and has a
      multitude of causes. This paper discusses a wide range of issues that have been
      identified as being relevant to this situation, and they are elaborated from a
      number of viewpoints, including that of health information management. In this
      article suggestions for changes that could help rectify this situation are made.

PMID- 28758515
TI  - Approaches for discovering novel bioactive small molecules targeting autophagy.
AB  - INTRODUCTION: In recent years, development of novel bioactive small molecules
      targeting autophagy has been implicated for autophagy-related disease treatment.
      Screening new small molecules regulating autophagy allows for the discovery of
      novel autophagy machinery and therapeutic agents. Areas covered: Two major
      screening methods for novel autophagy modulators are introduced in this review,
      namely target based screening and phenotype based screening. With increasing
      attention focused on chemical compound libraries, coupled with the development of
      new assay systems, this review attempts to provide an efficient strategy to
      explore autophagy biology and discover small molecules for the treatment of
      autophagy-related diseases. Expert opinion: Adopting an appropriate autophagy
      screening strategy is important for developing small molecules capable of
      treating neurodegenerative diseases and cancers. Phenotype based screening and
      target based screening were both used for developing effective small molecules.
      However, each of these methods has many pros and cons. An efficient approach is
      suggested to screen for novel lead compounds targeting autophagy, which could
      provide new hits with better efficiency and rapidity.

PMID- 28758516
TI  - Measurement properties of the WheelCon for powered wheelchair users.
AB  - PURPOSE: To evaluate the measurement properties of the Wheelchair Use Confidence
      Scale for power wheelchair users (WheelCon-P). DESIGN: One-month test-retest
      design, using data from a longitudinal study of power wheelchair use.
      PARTICIPANTS: Volunteer sample of 73 community dwelling, older adult experienced
      power wheelchair users who had a mean age of 60.5 +/- 7.1 years. METHODS:
      Participants completed the WheelCon-P twice to assess retest reliability.
      Concurrent validity was assessed by evaluating hypothesized relationships between
      the WheelCon-P and relevant variables. RESULTS: The baseline mean (standard
      deviation) WheelCon-P score was 78.8 +/- 14.5. Cronbach's alpha was 0.92. The one
      month test-retest intraclass correlation coefficient was 0.85 (CI 0.77-0.90).
      Correlations ranging from r = 0.26 (social support) to r = 0.49 (wheelchair
      skills) were found between the WheelCon-P and the validation outcome measures.
      CONCLUSION: The WheelCon-P has high internal consistency, strong retest
      reliability and evidence supporting its validity. Although further work is
      needed, the WheelCon-P may serve as a useful clinical and research tool for
      measuring power wheelchair confidence. Implications for rehabilitation The
      WheelCon-P is a reliable and valid outcome measure for assessing wheelchair
      confidence. This tool can be used to identify individuals with low power
      wheelchair confidence who require a confidence-enhancing intervention.

PMID- 28758517
TI  - The Wheelchair Use Confidence Scale: Italian translation, adaptation, and
      validation of the short form.
AB  - OBJECTIVE: We developed an Italian version of the Wheelchair Use Confidence Scale
      for Manual Users-Short Form (WheelCon-M-I-short form) and examined its
      reliability and validity. METHODS: The original scale was translated from English
      to Italian using the "Translation and Cultural Adaptation of Patient Reported
      Outcomes Measures-Principles of Good Practice" guidelines. The WheelCon-M-I-short
      form was administered to experienced manual wheelchair users who had a variety of
      diagnoses. Its internal consistency and test-retest reliability were examined.
      Its concurrent validity was evaluated using Pearson correlation coefficients with
      the Italian version of the Wheelchair Outcome Measure (WhOM-I) and the Italian
      version of the Barthel index (BI). RESULTS: The WheelCon-M-I-short form was
      administered to 31 subjects. The mean +/- SD of the WheelCon-M-I-short form score
      was 7.5 +/- 1.9. All WheelCon-M-I-short form items were either identical or
      similar in meaning to the WheelCon-M-short form items. Cronbach's alpha for the
      WheelCon-M-I-short form was 0.95 (p < 0.01), and the test-retest reliability
      (ICC) was 0.978 (p < 0.01). The Pearson correlation coefficient of the WheelCon-M
      I-short form scores with the WhOM-I scores was 0.7618 (p < 0.01). The Pearson
      correlation coefficient of the WheelCon-M-I-short form scores with the Italian BI
      scores was 0.638 (p < 0.01). CONCLUSIONS: The WheelCon-M-I-short form was found
      to be reliable and a valid outcome measure for assessing manual wheelchair
      confidence in the Italian population. Implication for Rehabilitation The WheelCon
      M-I-short form is a valid outcome measure available for assessing wheelchair
      confidence, according to Bandura's social cognitive theory, self-efficacy is a
      better predictor of future behavior than skill itself. Translation of the
      WheelCon-M-short form into the WheelCon-M-I-short form provides a new tool for
      Italian professionals. Clinicians now have a method to measure this invisible
      barrier to wheelchair use, and they will be able to make informed decisions when
      prescribing the use of manual wheelchairs and when training clients in their use.
      The WheelCon-M-I-short form also provides researchers with a tool in an important
      and relevant area of study for future research.

PMID- 28758518
TI  - Allometric scaling of power-force-velocity ergometry profiles in men.
AB  - AIM: To examine the appropriate magnitude of allometric scaling of the force
      velocity relationship according to body dimensions and to establish normative
      data for the power-force-velocity relationship for active men. SUBJECTS AND
      METHODS: Ninety-seven participants completed a force-velocity test on a Monark
      cycle ergometer. Allometric exponents and percentile ranks were established for
      maximal power (Pmax), maximal force (F0) and maximal velocity (V0). RESULTS: The
      mean (+/- SD) of Pmax, F0 and V0 were 1114.90 +/- 160.60 W, 191.97 +/- 26.51 N,
      and 227.87 +/- 8.82 rpm, respectively. V0 was not related to any body size
      descriptors. Allometric exponents for Pmax, and F0 scaled for body mass were b =
      0.77 (0.64-0.90) and 0.74 (0.61-0.86), respectively. Correlations between
      allometrically scaled Pmax and F0 with body mass were r = 0.002 (p = 0.984) and r
      = 0.008 (p = 0.940), respectively, suggesting that the allometric exponents
      derived were effective in partialling out the effect of body mass on Pmax and F0
      results. CONCLUSIONS: The allometric exponents and normative values of the
      current study provide a useful tool for comparing the scores of force-velocity
      tests between individuals without the confounding effect of body size.

PMID- 28758519
TI  - Perturbation During Treadmill Training Improves Dynamic Balance and Gait in
      Parkinson's Disease: A Single-Blind Randomized Controlled Pilot Trial.
AB  - BACKGROUND: Gait and balance dysfunction are major symptoms in Parkinson's
      disease (PD). Treadmill training improves gait characteristics in this population
      but does not reflect the dynamic nature of controlling balance during ambulation
      in everyday life contexts. OBJECTIVE: To evaluate whether postural perturbations
      during treadmill walking lead to superior effects on gait and balance performance
      compared with standard treadmill training. METHODS: In this single-blind
      randomized controlled trial, 43 PD patients (Hoehn & Yahr stage 1-3.5) were
      assigned to either an 8-week perturbed treadmill intervention (n = 21) or a
      control group (n = 22) training on the identical treadmill without perturbations.
      Patients were assessed at baseline, postintervention, and at 3 months' follow-up.
      Primary endpoints were overground gait speed and balance (Mini-BESTest).
      Secondary outcomes included fast gait speed, walking capacity (2-Minute Walk
      Test), dynamic balance (Timed Up-and-Go), static balance (postural sway), and
      balance confidence (Activities-Specific Balance Confidence [ABC] scale). RESULTS:
      There were no significant between-group differences in change over time for the
      primary outcomes. At postintervention, both groups demonstrated similar
      improvements in overground gait speed ( P = .009), and no changes in the Mini
      BESTest ( P = .641). A significant group-by-time interaction ( P = .048) existed
      for the Timed Up-and-Go, with improved performance only in the perturbation
      group. In addition, the perturbation but not the control group significantly
      increased walking capacity ( P = .038). Intervention effects were not sustained
      at follow-up. CONCLUSIONS: Our primary findings suggest no superior effect of
      perturbation training on gait and balance in PD patients. However, some favorable
      trends existed for secondary gait and dynamic balance parameters, which should be
      investigated in future trials.

PMID- 28758520
TI  - Unintended side effects of a spotless mind: theory and practice.
AB  - Forgetting can be either a source of great frustration or one of great relief,
      depending on whether the memories in question are relevant to one's immediate
      goals. Adopting an appropriate strategy or memory mode can help achieve these
      goals. But do efforts to control memory engender unintended side effects?
      Presently, we expand on a theoretical perspective of memory control, wherein
      efforts to suppress episodic encoding or retrieval result in the systemic
      downregulation of the hippocampal memory system. We review evidence from multiple
      methodologies, highlighting a non-invasive means of inducing amnesia that casts a
      shadow over memory for unrelated events. By establishing the causes and
      consequences of the amnesic side effects associated with memory control, we argue
      it may be possible to harness hippocampal dynamics to promote more adaptive
      memory performance in the lab, clinic, and broader context of daily life.

PMID- 28758521
TI  - Effectiveness of Human Research Protection Program Performance Measurements.
AB  - We analyzed human research protection program performance metric data of all
      Department of Veterans Affairs research facilities obtained from 2010 to 2016.
      Among a total of 25 performance metrics, 21 (84%) showed improvement, four (16%)
      remained unchanged, and none deteriorated during the study period. The overall
      improvement from these 21 performance metrics was 81.1% +/- 18.7% (mean +/- SD),
      with a range of 30% to 100%. The four performance metrics that did not show
      improvement all had initial noncompliance/incidence rates of <1.0%, ranging from
      0% to 0.98%. The initial noncompliance/incidence rates of the 21 performance
      metrics that showed improvement ranged from 0.05% to 60%. However, of the 21
      performance metrics that showed improvement, 10 had initial
      noncompliance/incidence rates of <1.0%, suggesting that improvement could be
      achieved even with a very low initial noncompliance/incidence rate. We conclude
      that performance measurement is an effective tool in improving the performance of
      human research protection programs.

PMID- 28758522
TI  - Explanatory models and distress in primary caregivers of patients with acute
      psychotic presentations: A study from South India.
AB  - BACKGROUND: Emotional distress among caregivers of people with mental illness is
      common, changes overtime and requires appropriate coping strategies to prevent
      long-term disability. Explanatory models, which underpin understanding of disease
      and illness, are crucial to coping. AIM: To study the association of explanatory
      models and distress among caregivers of people with acute psychotic illness.
      METHOD: A total of 60 consecutive patients and their primary caregivers who
      presented to the Department of Psychiatry, Christian Medical College, Vellore,
      were recruited for the study. Positive and Negative Syndrome Scale (PANSS), Short
      Explanatory Model Interview (SEMI) and the General Health Questionnaire-12 (GHQ
      12) were used to assess severity of psychosis, explanatory models of illness and
      emotional distress. Standard bivariate and multivariable statistics were
      employed. RESULTS: Majority of the caregivers simultaneously held multiple models
      of illness, which included medical and non-medical perspectives. The GHQ-12 score
      were significantly lower in people who held multiple explanatory models of
      illness when compared to the caregivers who believed single explanations.
      CONCLUSION: Explanatory models affect coping in caregivers of patients with acute
      psychotic presentations. There is a need to have a broad-based approach to
      recovery and care.

PMID- 28758523
TI  - Twelve tips to avoid ethical pitfalls when recruiting students as subjects in
      medical education research.
AB  - Medical education research has unique characteristics that raise their own set of
      ethical issues, which differ significantly from those commonly found in clinical
      research. In contexts where researchers have a dual role as teachers, free
      consent to participate in research may be undermined and students' data must be
      kept confidential from faculty who play any role in their academic or
      professional path. Faculty members who recruit students as research subjects
      within their institution for education research should pay particular attention
      to ensure students' consent to participate is indeed free and continuous and that
      their privacy is adequately protected. A good understanding of ethical standards
      and of the appropriate strategies to fulfill them is essential to conduct ethical
      medical education research and to ensure ethics approval is obtained. These
      twelve tips draw from the Declaration of Helsinki, from the ICMJE recommendations
      and from the example of their application to medical education research in a
      Canadian and North American context. They aim to act as a reminder and as a guide
      to address the main ethical issues which should be given proper consideration
      when designing a study involving students as subjects for medical education
      research.

PMID- 28758525
TI  - The Model for Assessment of Telemedicine (MAST): A scoping review of empirical
      studies.
AB  - The evaluation of telemedicine can be achieved using different evaluation models
      or theoretical frameworks. This paper presents a scoping review of published
      studies which have applied the Model for Assessment of Telemedicine (MAST). MAST
      includes pre-implementation assessment (e.g. by use of participatory design),
      followed by multidisciplinary assessment, including description of the patients
      and the application and assessment of safety, clinical effectiveness, patient
      perspectives, economic aspects organisational aspects and socio-cultural, legal
      and ethical aspects. Twenty-two studies met the inclusion criteria and were
      included in the review. In this article, research design and methods used in the
      multidisciplinary assessment are described, strengths and weaknesses are
      analysed, and recommendations for future research are presented.

PMID- 28758524
TI  - Transit time homogenization in ischemic stroke - A novel biomarker of penumbral
      microvascular failure?
AB  - Cerebral ischemia causes widespread capillary no-flow in animal studies. The
      extent of microvascular impairment in human stroke, however, is unclear. We
      examined how acute intra-voxel transit time characteristics and subsequent
      recanalization affect tissue outcome on follow-up MRI in a historic cohort of 126
      acute ischemic stroke patients. Based on perfusion-weighted MRI data, we
      characterized voxel-wise transit times in terms of their mean transit time (MTT),
      standard deviation (capillary transit time heterogeneity - CTH), and the CTH:MTT
      ratio (relative transit time heterogeneity), which is expected to remain constant
      during changes in perfusion pressure in a microvasculature consisting of passive,
      compliant vessels. To aid data interpretation, we also developed a computational
      model that relates graded microvascular failure to changes in these parameters.
      In perfusion-diffusion mismatch tissue, prolonged mean transit time (>5 seconds)
      and very low cerebral blood flow (<=6 mL/100 mL/min) was associated with high
      risk of infarction, largely independent of recanalization status. In the
      remaining mismatch region, low relative transit time heterogeneity predicted
      subsequent infarction if recanalization was not achieved. Our model suggested
      that transit time homogenization represents capillary no-flow. Consistent with
      this notion, low relative transit time heterogeneity values were associated with
      lower cerebral blood volume. We speculate that low RTH may represent a novel
      biomarker of penumbral microvascular failure.

PMID- 28758526
TI  - Examining Predictive Validity of Oral Reading Fluency Slope in Upper Elementary
      Grades Using Quantile Regression.
AB  - Within multitiered instructional delivery models, progress monitoring is a key
      mechanism for determining whether a child demonstrates an adequate response to
      instruction. One measure commonly used to monitor the reading progress of
      students is oral reading fluency (ORF). This study examined the extent to which
      ORF slope predicts reading comprehension outcomes for fifth-grade struggling
      readers ( n = 102) participating in an intensive reading intervention. Quantile
      regression models showed that ORF slope significantly predicted performance on a
      sentence-level fluency and comprehension assessment, regardless of the students'
      reading skills, controlling for initial ORF performance. However, ORF slope was
      differentially predictive of a passage-level comprehension assessment based on
      students' reading skills when controlling for initial ORF status. Results showed
      that ORF explained unique variance for struggling readers whose posttest
      performance was at the upper quantiles at the end of the reading intervention,
      but slope was not a significant predictor of passage-level comprehension for
      students whose reading problems were the most difficult to remediate.

PMID- 28758527
TI  - Sleep Habits, Sleep Problems, Sleep Hygiene, and Their Associations With Mental
      Health Problems Among Adolescents.
AB  - BACKGROUND: Studies in adults suggested that sleep could be a significant
      contributor to mental health. However, little is known about their relationship
      in adolescents. OBJECTIVE: The present study aimed to examine the overall
      associations of full-spectrum sleep behaviors, including sleep habits, sleep
      problems, and sleep hygiene, with mental health problems among adolescents in
      Shanghai, China. DESIGN: A stratified, cluster random sample of 4,823 adolescents
      aged 11 to 20 years participated in a cross-sectional survey. The Adolescent
      Sleep Disturbance Questionnaire and the modified Adolescent Sleep Hygiene Scale
      were used to examine sleep behaviors. The Strengths and Difficulties
      Questionnaire was used to evaluate mental health problems. RESULTS: Five sleep
      variables were found to be associated with adolescents' mental health. The five
      factors covered three sleep domains: sleep habits (later bedtime during
      weekdays), sleep problems (maintaining sleep difficulties, disorders of arousal),
      and sleep hygiene (poor emotion at bedtime, unstable sleep schedule).
      CONCLUSIONS: The clinical significance of the findings lies in the emphasis of
      comprehensive screening of sleep in the predicting, diagnosis, nursing, and
      intervention of adolescents' mental health problems.

PMID- 28758528
TI  - The influence of late displacement in distal radius fractures on function, grip
      strength, range of motion and quality of life.
AB  - : Late displacement of distal radius fractures, still in acceptable radiological
      position after 1-2 weeks, occurs in approximately one-third of cases. The aim of
      this study was to investigate the influence of late displacement on the
      functional outcome and quality of life at 1 year in non-operatively treated
      distal radius fractures. One hundred and seventy five unilateral conservatively
      treated distal radius fractures with minimal displacement after 10-14 days were
      finally evaluated in the study. Follow-up included radiographs at 3 months and
      clinical examination 1 year after the fracture. Final radiographic parameters,
      grip strength, range of motion, QuickDASH, EQ-5D and pain visual analogue scale
      were evaluated with multivariate analysis. Late displacement occurred in 28% of
      the cases and was associated with loss of grip strength and range of motion. No
      significant differences were seen in the outcome questionnaires. LEVEL OF
      EVIDENCE: II.

PMID- 28758529
TI  - Targeting endothelin-1 receptor/beta-arrestin1 network for the treatment of
      ovarian cancer.
AB  - INTRODUCTION: Endothelin-1 receptor (ET-1R)/beta-arrestin1 (beta-arr1) signaling
      is dysregulated in ovarian cancer. This signaling circuit enables cancer cells to
      engage several signaling and transcriptional networks that are pervasively
      intertwined, and represent a potential therapeutic target for developing novel
      agents for ovarian cancer treatment. Areas covered: In this article, we discuss
      the role of the signaling network between ET-1R and key pathways mediated by the
      scaffold protein beta-arr1, as part of signaling complex, or as a transcription
      co-activator, promoting precise control of transcription of different genes,
      including ET-1. Therefore ET-1R/beta-arr1 is an actionable node involved in the
      activation of a persistent feedback loop that contributes to bypass signaling.
      Targeting ET-1R empowering this circuit can represent a necessary measure to
      reach clinical efficacy. Preclinical studies demonstrate that blocking ET-1R by
      FDA approved dual ETAR/ETBR antagonist prevents beta-arr1 network formation,
      offering a novel therapeutic strategy in ovarian cancer patients. Expert opinion:
      The information provided in this review about the ET-1R/beta-arr1 hub represents
      an invaluable tool for both identifying the interconnected pathways involved in
      ovarian cancer and targeting them more effectively. The new perspective arising
      from ET-1R therapeutics will likely prompt a valuable frame for the design of new
      promising combinatorial therapy, blocking compensatory networks.

PMID- 28758531
TI  - Early versus delayed amniotomy during labor induction with oxytocin in women with
      Bishop's score of >=6: a randomized trial.
AB  - OBJECTIVE: To study the effect of "early amniotomy" {initiating induction of
      labor (IOL) with amniotomy followed by oxytocin} versus "late amniotomy"
      (initiating IOL with oxytocin followed by amniotomy 4-8 h later) in induced
      labor. METHODS AND MATERIALS: One hundred and fifty women with Bishop's score of
      >=6 undergoing IOL were randomized into "early amniotomy" and "delayed
      amniotomy". RESULTS: Early amniotomy resulted in a reduced induction-delivery
      interval (IDI) (7.35 versus 11.66 h with delayed amniotomy, p = .000) but higher
      the caesarean section (CS) rate was observed (10.7 versus 2.7% with delayed
      amniotomy, p = .049). With early amniotomy, the proportion of women delivering
      within 12 h was higher (86.7 versus 60%, p = .000) and the maximum oxytocin
      concentration used was lower (30.05 versus 39.68 mU/min, p = .001) as compared to
      delayed amniotomy. The neonatal outcomes were similar in the two groups. Early
      amniotomy detected meconium prior to initiating uterine contractions with
      oxytocin in three women who underwent CS for meconium. CONCLUSION: Initiating IOL
      with amniotomy in women with a favorable cervix was efficacious in expediting
      delivery, but it resulted in a higher CS rate. The higher CS rate was partly due
      to CS for meconium detected as a result of early amniotomy. Clinical Trials
      Registry (CTRI), India: Registration number CTRI/2015/01/005418.

PMID- 28758530
TI  - An optimised spectrophotometric assay for convenient and accurate quantitation of
      intracellular iron from iron oxide nanoparticles.
AB  - We report the development and optimisation of an assay for quantitating iron from
      iron oxide nanoparticles in biological matrices by using ferene-s, a chromogenic
      compound. The method is accurate, reliable and can be performed with basic
      equipment common to many laboratories making it convenient and inexpensive. The
      assay we have developed is suited for quantitation of iron in cell culture
      studies with iron oxide nanoparticles, which tend to manifest low levels of iron.
      The assay was validated with standard reference materials and with inductively
      coupled plasma-mass spectrometry (ICP-MS) to accurately measure iron
      concentrations ~1 * 10-6 g in about 1 * 106 cells (~1 * 10-12 g Fe per cell). The
      assay requires preparation and use of a working solution to which samples can be
      directly added without further processing. After overnight incubation, the
      absorbance can be measured with a standard UV/Vis spectrophotometer to provide
      iron concentration. Alternatively, for expedited processing, samples can be
      digested with concentrated nitric acid before addition to the working solution.
      Optimization studies demonstrated significant deviations accompany variable
      digestion times, highlighting the importance to ensure complete iron ion
      liberation from the nanoparticle or sample matrix to avoid underestimating iron
      concentration. When performed correctly, this method yields reliable iron ion
      concentration measurements to ~2 * 10-6 M (1 * 10-7 g/ml sample).

PMID- 28758532
TI  - A multi-perspective evaluation of a service robot for seniors: the voice of
      different stakeholders.
AB  - PURPOSE: The potential of service robots for seniors is given increasing
      attention as the ageing population in Western countries will continue to grow as
      well as the demand for home care. In order to capture the experience of living
      with a robot at home, a multi-perspective evaluation was conducted. METHODS:
      Older adults (n = 10) were invited to execute an actual interaction scenario with
      the Care-O-bot(r) robot in a home-like environment and were questioned about
      their experiences. Additionally, interviews were conducted with the elderly
      participants, informal carers (n = 7) and professional caregivers (n = 11).
      RESULTS: Seniors showed to be more keen to accept the robot than their caregivers
      and relatives. However, the robot in its current form was found to be too limited
      and participants wished the robot could perform more complex tasks. In order to
      be acceptable a future robot should execute these complex tasks based on the
      personal preferences of the user which would require the robot to be flexible and
      extremely smart, comparable to the care that is delivered by a human carer.
      CONCLUSIONS: Developing the functional features to perform activities is not the
      only challenge in robot development that deserves the attention of robot
      developers. The development of social behaviour and skills should be addressed as
      well. This is possible adopting a person-centred design approach, which relies on
      validation activities with actual users in realistic environments, similar to
      those described in this paper. Implications for rehabilitation Attitude of older
      adults towards service robots Potential of service robotsfor older adults.

PMID- 28758533
TI  - Laparoscopic early pregnancy diagnosis in the laboratory rat.
AB  - Timely and accurate diagnosis of pregnancy in the laboratory rat is an invaluable
      endpoint in embryological and reproductive toxicology studies. The purpose of the
      present study was to assess the feasibility, sensitivity, accuracy and safety of
      laparoscopic examination of the uterus for detecting pregnancy at an early stage,
      and defining the number of fetuses in surviving rat models. Female Wistar rats
      were subjected to a two-port laparoscopic examination of their uterus from day 6
      to day 10 post-coitum (pc). Mean recovery time from anesthesia was 148 +/- 66 s.
      A postoperative 4.0 +/- 1.8% body weight loss was restored in 3.9 +/- 1.3 days.
      Uterine bulges suggestive of underlying embryonic vesicles could be detected by
      day 7 pc with a 0% false-negative diagnosis. Comparison of the number of
      laparoscopically defined uterine bulges (fetal counts) with litter size revealed
      a 0% underestimation rate of fetal counts, and a 42.9-87.5% overestimation rate
      from day 7 to day 10 pc. In conclusion, the present study introduced the
      laparoscopic examination of the uterus and showed it to be a feasible, reliable
      and safe method of early pregnancy diagnosis in the laboratory rat by day 7 pc.

PMID- 28758534
TI  - Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal
      writhing without affecting immunohistochemical endpoints in rats.
AB  - Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats,
      however its high pH can cause abdominal discomfort after intraperitoneal
      injection. Previous studies suggest that the addition of a local anaesthetic may
      alleviate this discomfort, but the practice has not been widely adopted. We
      examined the effect of combining lidocaine with pentobarbital on abdominal
      writhing, defecation, ultrasonic vocalizations, the rat grimace scale and
      immunohistochemical staining for c-Fos in the nucleus accumbens and basolateral
      amygdala of the brain. We also compared the amount of abdominal writhing
      following intraperitoneal administration of pentobarbital-lidocaine with that of
      pentobarbital-bupivacaine. Our results show that lidocaine reduces abdominal
      writhing and defecation without affecting immunohistochemistry for c-Fos or
      latency to loss of posture. However, scores on the rat grimace scale were low in
      both situations and almost no ultrasonic vocalizations were recorded.
      Additionally, we found that the amount of abdominal writhing was not
      significantly different when bupivacaine was used rather than lidocaine. Our
      results suggest that pentobarbital-induced euthanasia can be refined with the
      addition of lidocaine or other local anaesthetics.

PMID- 28758535
TI  - A comparative analysis of maternal and fetal 25-hydroxyvitamin D in pregnant
      women with and without gestational diabetes mellitus.
AB  - OBJECTIVE: This study aimed to compare maternal 25-hydroxyvitamin D (25(OH)D)
      serum levels during pregnancy in women with and without gestational diabetes
      mellitus (GDM) with neonatal 25(OH)D serum levels and to evaluate the
      relationship between maternal and fetal 25(OH)D in the two groups. METHODS:
      Between May 2014 and March 2015, 87 pregnant women were enrolled. The study
      population was divided into two groups, those with and without GDM (n = 32 and
      55). All participants were surveyed about lifestyle and behavior. Maternal and
      umbilical venous blood samples were obtained. Serum from maternal blood was
      analyzed for 25(OH)D2 and 25(OH)D3, and umbilical venous blood for 25(OH)D2,
      25(OH)D3, and 3-epi-25(OH)D3. RESULTS: The maternal serum level of 25(OH)D3 and
      the 25(OH)D3 and 3-epi-25(OH)D3 levels in umbilical venous blood were
      significantly lower in women with GDM (p < .01 for all comparisons). The maternal
      blood levels of 25(OH)D2, 25(OH)D3, and total 25(OH)D were positively correlated
      with their levels in umbilical venous blood in the total, normal, and GDM groups.
      CONCLUSIONS: The serum 25(OH)D3 and 3-epi-25(OH)D3 levels of babies from mothers
      with GDM are lower than in pregnant women without GDM.

PMID- 28758536
TI  - Gynecomastia: glandular-liposculpture through a single transaxillary one hole
      incision.
AB  - Gynecomastia is characterized by the benign proliferation of breast tissue in
      men. Herein, we present a new method for the treatment of gynecomastia, using
      ultrasound-assisted liposuction with both conventional and reverse-cutting edge
      tip cannulas in combination with a pull-through lipectomy technique with
      pituitary forceps through a single transaxillary incision. Thirty patients were
      treated with this technique at the author's institution from January 2010 to
      January 2015. Ten patients were treated with conventional surgical excision of
      the glandular/fibrous breast tissue combined with liposuction through a
      periareolar incision before January 2010. Medical records, clinical photographs
      and linear analog scale scores were analyzed to compare the surgical results and
      complications. The patients were required to rate their cosmetic outcomes based
      on the linear analog scale with which they rated their own surgical results; the
      mean overall average score indicated a good or high level of satisfaction. There
      were no incidences of skin necrosis, hematoma, infection and scar contracture;
      however, one case each of seroma and nipple inversion did occur. Operative time
      was reduced overall using the new technique since it is relatively simple and
      straightforward. According to the evaluation by the four independent researchers,
      the patients treated with this new technique showed statistically significant
      improvements in scar and nipple-areolar complex (NAC) deformity compared to those
      who were treated using the conventional method. Glandular liposculpture through a
      single transaxillary incision is an efficient and safe technique that can provide
      aesthetically satisfying and consistent results.

PMID- 28758537
TI  - Human Perception of Animacy in Light of the Uncanny Valley Phenomenon.
AB  - The uncanny valley hypothesis by Japanese roboticist Masahiro Mori posits a
      nonlinear relation between human replicas' human likeness and the emotional
      responses they elicit. In three studies, we corroborated the uncanny valley
      hypothesis, using the uncanny phenomenon as a vehicle to shed a new light on
      human animacy perception. In Study 1, 62 participants rated emotional responses
      and human likeness of 89 artificial and human faces. In Study 2, another 62
      participants conducted a visual looming task with the same 89 faces allowing for
      the measurement of perceived threat. Results support the uncanny valley
      hypothesis, suggesting that the uncanny feeling may serve a function to wary
      humans of the potential danger of entities crossing the animate-inanimate
      boundary. In Study 3, 36 participants sorted faces as either real or unreal as
      quickly as possible in a reaction time sorting task allowing for the measurement
      of categorical uncertainty associated with animacy perception. Faces associated
      with longer sorting reaction times were also those associated with the highest
      ratings of negative emotions, suggesting that categorical uncertainty in animacy
      detection is related to the uncanny feeling. Results are discussed in light of
      human animacy perception and new directions for future research are suggested.

PMID- 28758539
TI  - Julia Carter, Health Information Manager, Queensland Royal Flying Doctor Service.

PMID- 28758538
TI  - "You Can Only Give Warmth to Your Baby When It's Too Late": Parents' Bonding With
      Their Extremely Preterm and Dying Child.
AB  - This study on end-of-life decisions in extremely preterm babies shows that the
      parents under study experience a multitude of stressors due to the immediate
      separation after birth, the alienating setting of the neonatal intensive care
      unit (NICU), the physical distance to the child, medical uncertainties, and
      upcoming decisions. Even though they are considered to be parents (assigned
      parenthood), they cannot act as primary caregivers. Instead, they depend on
      professional instructions for access and care. Embodied parenthood can be
      experienced only at the end-of-life, that is, during the dying trajectory and
      after the child's death. Professionally supporting parents during this compressed
      process (from assigned and distant to embodied parenthood) contributes
      fundamentally to their perception of being a family and supports their mourning.
      This calls for the further establishment of palliative and bereavement care
      concepts in neonatology.

PMID- 28758540
TI  - Using the theoretical domains framework to guide the development of a self
      management program for individuals with spinal cord injury: Results from a
      national stakeholder advisory group.
AB  - OBJECTIVE: To determine the implementation considerations for a targeted self
      management program for individuals with spinal cord injury (SCI) from the
      perspective of a national stakeholder advisory group using the Theoretical
      Domains Framework (TDF) as a guide. DESIGN: Qualitative descriptive approach.
      SETTING: Two focus groups held at the 6th National Spinal Cord Injury Conference
      (October 2-4th, 2014) in Toronto, Ontario, Canada. PARTICIPANTS: A total of 25
      stakeholders from across Canada participated in focus groups or "brainstorming
      sessions". The stakeholders included 5 clinicians, 14 researchers, 3 policy
      makers, and 3 individuals with SCI. INTERVENTIONS: Not applicable. OUTCOME
      MEASURES: Not applicable. RESULTS: All 14 theoretical domains were identified in
      the brainstorming sessions. No new themes or domains were identified. The need to
      consider the theoretical domains of Knowledge, Skills, Reinforcement, Intentions,
      Goals (e.g. the readiness of the individual with SCI), Environmental Context and
      Resources (e.g. considerations for governance and ownership of the program and a
      business model for sustainability), as well as Social Influences (e.g. issues of
      privacy and security in the context of on-line delivery) was identified.
      CONCLUSIONS: The current study provides complementary results to our previous
      series of studies on the implementation considerations for the development of a
      targeted self-management program for individuals with SCI by emphasizing the
      health care professional/health policy perspective. It is anticipated that such a
      program could not only reduce secondary complications and subsequent
      inappropriate health care use but it may also improve the quality of life for
      individuals with SCI and their caregivers.

PMID- 28758542
TI  - Cost-effectiveness of a day-camp weight-loss intervention programme for children:
      Results based on a randomised controlled trial with one-year follow-up.
AB  - AIMS: The aim was to analyse the cost-effectiveness of an intensive weight-loss
      intervention for children compared with a low-intensity intervention. METHODS:
      One hundred and fifteen overweight children (mean age 12.0 +/- 0.4) were
      randomised to either the camp group (CG) ( N=59) or the standard group (SG) (
      N=56). Participants in the CG were offered a six-week day-camp weight-loss
      programme followed by a family-based supportive programme containing four
      meetings during the succeeding 46 weeks. Participants in the SG were offered a
      weekly two-hour exercise session for six weeks. Changes in body mass index (BMI)
      and BMI z-score 12 months after inclusion were used to compare the effects of the
      two interventions. Incremental cost-effectiveness ratios (ICER) were estimated
      from the perspective of a Danish municipality. To achieve the required number of
      participants, an additional intervention was initiated one year later. RESULTS:
      In comparison with the SG, the CG changed their mean BMI by -1.2 (95% CI -1.8 to 
      0.5). Compared with the SG children, the CG children changed their BMI z-score by
      -0.20 (95% CI -0.35 to -0.05). The ICER per decreased BMI point in the CG
      compared with the SG was DDK 24,928. CONCLUSIONS: Compared with the SG, the CG
      showed favourable effects after 12 months. However, the CG was more costly. The
      results observed in the present study may be helpful in guiding decision makers
      to take more informed decisions when choosing different types of intervention.

PMID- 28758543
TI  - Inconsistencies with Screening for Traumatic Brain Injury in Spinal Cord Injury
      across the Continuum of Care.
AB  - OBJECTIVE: Explore how traumatic brain injury (TBI) is screened among spinal cord
      injury (SCI) patients across the continuum of care. DESIGN: Retrospective chart
      review Setting: Emergency department, trauma, inpatient rehabilitation
      Participants: 325 patients with SCI from inpatient rehabilitation facility (IRF)
      between March 1, 2011 and December 31, 2014 were screened. 49 eligible subjects
      had traumatic SCI and received care in adjoining acute care (AC) hospital.
      OUTCOME MEASURES: Demographic characteristics and variables that capture
      diagnosis of TBI/SCI included documentation from ambulance, emergency department,
      AC, and IRF including ICD-9 codes, altered mental status, loss of consciousness
      (LOC), Glasgow Coma Score, Post Traumatic Amnesia (PTA), neuroimaging, and
      cognitive assessments. RESULTS: Participants were male (81%), white (55%),
      privately insured (49%), and aged 39.3+/-18.0 years with 51% paraplegic and 49%
      tetraplegic. Mechanisms of injury were gunshot wound (31%), fall (29%), and motor
      vehicle accident (20%). TBI occurred in 65% of SCI individuals, however
      documentation of identification of TBI, LOC, and CT imaging results varied in
      H&P, discharge notes, and ICD-9 codes across the continuum. Cognitive assessments
      were performed on 16% of subjects. CONCLUSIONS: Documentation showed variability
      between AC and IRF and among disciplines. Imaging and GCS were more consistently
      documented than LOC and PTA. It is necessary to standardize screening processes
      between AC and IRF to identify dual diagnosis.

PMID- 28758541
TI  - Cobra neurotoxin produces central analgesic and hyperalgesic actions via
      adenosine A1 and A2A receptors.
AB  - Cobra neurotoxin, a short-chain peptide isolated from snake venom of Naja naja
      atra, showed both a central analgesic effect and a hyperalgesic effect in mice
      tests. In order to explore mechanisms, a hypothesis is put forward that cobra
      neurotoxin takes effect through adenosine receptor pathway. The central effects
      of cobra neurotoxin were evaluated using the hot plate test (a model of acute
      pain) and the spinal cord injury (a model of central pain) in mice and using A1
      receptor antagonist (DPCPX) and A2A receptor antagonist (ZM241385); behaviors
      were scored and signal molecules such as reactive oxygen species and adenosine
      triphosphate levels and mitogen-activated protein kinases/extracellular signal
      regulated protein kinase expression were measured. Low dose of cobra neurotoxin
      (25 ug/kg) had analgesic effects which were inhibited by DPCPX, while high dose
      of cobra neurotoxin (100 ug/kg) had hyperalgesic effects which were blocked by
      ZM241385. Cobra neurotoxin reduced reactive oxygen species and increased
      adenosine triphosphate in brain tissues, and extracellular signal-regulated
      protein kinase expression was markedly inhibited by cobra neurotoxin. Cobra
      neurotoxin may take effect through mitogen-activated protein
      kinases/extracellular signal-regulated protein kinase pathway inhibition by
      activating adenosine A1Rs and cause changes of reactive oxygen species and
      adenosine triphosphate through feedback mechanisms. Overdose cobra neurotoxin
      further activates the adenosine A2ARs to generate pain sensitization. This
      research proposes a new central analgesic mechanism of cobra neurotoxin and
      discloses dual regulation of pain.

PMID- 28758544
TI  - What Facilitates "Patient Empowerment" in Cancer Patients During Follow-Up: A
      Qualitative Systematic Review of the Literature.
AB  - Empowerment is a concept of growing importance in cancer care, but little is
      known about cancer patients' experiences of empowerment during follow-up. To
      explore this area, a qualitative systematic literature review was conducted in
      PubMed, CINAHL, and PsycINFO. A total of 2,292 papers were identified and 38
      articles selected and included in the review. The thematic synthesis of the
      papers resulted in seven analytical themes being identified: empowerment as an
      ongoing process, knowledge is power, having an active role, communication and
      interaction between patients and health care professionals, support from being in
      a group, religion and spirituality, and gender. Very few articles explicitly
      explored the empowerment of cancer patients during follow-up, and the review
      identified a lack of attention to patients' own understandings of empowerment, a
      lack of specific focus on empowerment during follow-up, and insufficient
      attention to collective empowerment, as well as ethnic, social, and gender
      differences.

PMID- 28758545
TI  - A topographical map approach to representing treatment efficacy: a focus on
      positive psychology interventions.
AB  - A recent meta-analysis by Bolier et al. indicated that positive psychology
      interventions have overall small to moderate effects on well-being, but results
      were quite heterogeneous across intervention trials. Such meta-analytic research
      helps condense information on the efficacy of a broad psychosocial intervention
      by averaging across many effects; however, such global averages may provide
      limited navigational guidance for selecting among specific interventions. Here,
      we introduce a novel method for displaying qualitative and quantitative
      information on the efficacy of interventions using a topographical map approach.
      As an initial prototype for demonstrating this method, we mapped 50 positive
      psychology interventions targeting well-being (as captured in the Bolier et al.
      [2013] meta-analysis, [Bolier, L., Haverman, M., Westerhof, G. J., Riper, H.,
      Smit, F., & Bohlmeijer, E. (2013). Positive psychology interventions: A meta
      analysis of randomized controlled studies. BMC Public Health, 13, 83]). Each
      intervention domain/subdomain was mapped according to its average effect size
      (indexed by vertical elevation), number of studies providing effect sizes
      (indexed by horizontal area), and therapist/client burden (indexed by shading).
      The geographical placement of intervention domains/subdomains was determined by
      their conceptual proximity, allowing viewers to gauge the general conceptual
      "direction" in which promising intervention effects can be found. The resulting
      graphical displays revealed several prominent features of the well-being
      intervention "landscape," such as more strongly and uniformly positive effects of
      future-focused interventions (including, goal-pursuit and optimism training)
      compared to past/present-focused ones.

PMID- 28758546
TI  - Poster abstracts P1 - P32.

PMID- 28758548
TI  - Health Information and Public Health.

PMID- 28758547
TI  - Design of a sensorized guiding catheter for in situ laser fenestration of
      endovascular stent.
AB  - PURPOSE: The in situ fenestration of a standard endograft is currently limited by
      difficulties in targeting the fenestration site under fluoroscopic control and by
      the lack of a safe method to perforate the graft. Evidence in the literature
      suggests the use of a 3 D electromagnetic navigator to accurately guide the
      endovascular instruments to the target and a laser to selectively perforate the
      graft. The aim of this work is to provide design guidelines to develop a
      sensorized catheter to guide the laser tool to the fenestration site and conduct
      preliminary testing of the feasibility of the proposed solution. Matherials and
      methods: Different catheter designs were delineated starting from engineering
      considerations, then prototypes were preliminarily tested to collect surgeon
      opinions and to steer the design process toward the preferred solution reported
      by the user. Finally, mechanical simulations were performed with CathCAD, a
      design software system for the development of composite tubing for endovascular
      catheters. RESULTS: Based on surgeon feedback, a 9-French steerable catheter with
      a stabilization system was designed. CathCAD simulations allowed us to define the
      construction parameters (e.g., materials and geometric constrains) for the
      fabrication of composite tubes with mechanical properties (flexural, axial, and
      torsional rigidities) compatible with target values in the literature for guiding
      catheters. CONCLUSION: The presented results preliminarily demonstrate the
      clinical reasonability and feasibility of the designed tool in terms of
      mechanical properties. Further mechanical tests and extensive in vitro clinical
      trials are required prior to animal testing.

PMID- 28758549
TI  - Pipeline embolization device retraction and foreshortening after internal carotid
      artery blister aneurysm treatment.
AB  - Background Subarachnoid hemorrhage (SAH) secondary to rupture of a blister
      aneurysm (BA) results in high morbidity and mortality. Endovascular treatment
      with the pipeline embolization device (PED) has been described as a new treatment
      strategy for these lesions. We present the first reported case of PED retraction
      and foreshortening after treatment of a ruptured internal carotid artery (ICA)
      BA. Case description A middle-aged patient presented with SAH secondary to ICA BA
      rupture. The patient was treated with telescoping PED placement across the BA.
      After 5 days from treatment, the patient developed a new SAH due to re-rupture of
      the BA. Digital subtraction angiography revealed an increase in caliber of the
      supraclinoid ICA with associated retraction and foreshortening of the PED that
      resulted in aneurysm uncovering and growth. Conclusions PED should be oversized
      during ruptured BA treatment to prevent device retraction and aneurysm regrowth.
      Frequent imaging follow up after BA treatment with PED is warranted to ensure
      aneurysm occlusion.

PMID- 28758551
TI  - Retention of a reconstructed nipple using a C-V flap with different layer
      thicknesses in the C-flap.
AB  - BACKGROUND: The C-V flap for nipple reconstruction is now one of standard
      surgical techniques. But decreased projection is still a problem. In recent
      years, it has been suggested that projection can be more easily maintained when
      raising of the C-flap is performed with a split thickness dermis. In this study,
      we examined whether decrease of projection can be prevented by raising of a C
      flap with a split dermis rather than with full dermis. METHODS: A total of 49
      consecutive patients who underwent reconstruction of a nipple using the C-V flap
      technique were enrolled. The patients included 22 who underwent surgery using a C
      flap with a full thickness dermis (Group F), and 27 who underwent surgery with
      raising of a flap with a split thickness dermis (Group S). The size of the
      reconstructed nipple was measured at 2 weeks, 6 months and 1 year postoperatively
      for comparison between Groups F and S. RESULTS: Partial necrosis of the C-flap
      end occurred in 4 subjects in only Group S. The decrease in projection after 1
      year postoperatively in Group S was significantly lower than that in Group F. In
      contrast, the teat base size in Group F tended to be greater than that in Group
      S, suggesting a tendency for an expanded base using a flap with a full dermis.
      CONCLUSIONS: Our results indicated that it is recommended to use a C-flap with a
      split dermis for cases with high projection of the nipple on the contralateral
      side.

PMID- 28758550
TI  - Treatment of ruptured blood blister aneurysms using primary flow-diverter
      stenting with considerations for adjunctive coiling: A single-centre experience
      and literature review.
AB  - Objective The objective of this article is to conduct a single-centre evaluation
      and quick literature review of the effectiveness of primary flow-diverter (FD)
      treatment of ruptured blood blister aneurysms (BBAs), with additional relevance
      of adjunctive coiling. Methods Patients presenting with subarachnoid haemorrhage
      (SAH) due to ruptured BBAs and subsequently treated with FDs were retrospectively
      selected from June 2010 to January 2017. Treatment techniques, angiographic data
      on occlusion rates and procedural success as well as clinical outcomes using the
      modified Rankin Scale (mRS) were collated. Cross-reference of results were made
      with available literature. Results Thirteen patients harbouring 14 BBAs were
      recruited. Of the 14 aneurysms, five (35.7%) showed immediate complete occlusion
      after the procedure (four of these five patients had adjunctive coiling). All of
      the aneurysms showed complete occlusion by the six- to nine-month control
      diagnostic angiogram. No rebleed or retreatment was experienced. Twelve of 13
      (92%) patients had an mRS score of 0-1 at the last clinical follow-up. From the
      pooled data of the literature review, eventual aneurysm occlusion was achieved in
      48/56 patients, with five patients requiring further endovascular treatment. In
      the clinical follow-up period, an mRS of 0-2 was recorded for 83.3% (45/54) of
      patients. Conclusion Endovascular reconstruction of BBAs using FD treatment is an
      effective method with good final clinical outcomes. Adjunctive use of coiling
      achieves higher incidence of immediate complete occlusion of BBAs.

PMID- 28758552
TI  - Correlation between HPV status at T and N sites of oropharyngeal squamous cell
      carcinomas.
AB  - OBJECTIVES: Human papilloma virus (HPV) is known to be associated with
      oropharyngeal squamous cell carcinomas (OPSCC) and may potentially play a vital
      role in tumor metastasis. The purpose of this study was to correlate HPV status
      of cervical lymph node metastases with their respective primary OPSCC tumor.
      METHODS: Formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from 34
      patients with cervical lymph node metastases were analyzed with HPV 16 DNA
      polymerase chain reaction (PCR), p16 immunohistochemistry and HPV typing. The
      results were correlated with the HPV status and type found in the primary tumors
      of OPSCC. RESULTS: Comparing HPV DNA status with p16 we found that 21 primary
      tumors and lymph node metastases were HPV positive (61.8%) and seven primary
      tumors and lymph node metastases were HPV negative (20.6%). Six patient samples
      differed when correlating the primary tumor and lymph node metastasis (17.6%).
      CONCLUSIONS: In this study, HPV status in OPSCCs and their cervical lymph node
      metastases correlated in the vast majority of cases. However, HPV detection
      methods may have certain limitations resulting in varying degree of non
      correlation. This should be taken into account when stratifying treatment in
      regard to HPV status.

PMID- 28758555
TI  - Sequential motion of the ossicular chain measured by laser Doppler vibrometry.
AB  - OBJECTIVE: In order to help a surgeon make the best decision, a more objective
      method of measuring ossicular motion is required. METHODS: A laser Doppler
      vibrometer was mounted on a surgical microscope. To measure ossicular chain
      vibrations, eight patients with cochlear implants were investigated. To assess
      the motions of the ossicular chain, velocities at five points were measured with
      tonal stimuli of 1 and 3 kHz, which yielded reproducible results. The sequential
      amplitude change at each point was calculated with phase shifting from the tonal
      stimulus. Motion of the ossicular chain was visualized from the averaged results
      using the graphics application. RESULTS: The head of the malleus and the body of
      the incus showed synchronized movement as one unit. In contrast, the stapes
      (incudostapedial joint and posterior crus) moved synchronously in opposite phase
      to the malleus and incus. The amplitudes at 1 kHz were almost twice those at 3
      kHz. CONCLUSIONS: Our results show that the malleus and incus unit and the stapes
      move with a phase difference.

PMID- 28758557
TI  - Thromboelastometry Versus Rotational Thromboelastography in Cardiac Surgery.
AB  - Evidence exists on the morbiduty and mortality associated with both massive blood
      loss and transfusion in cardiac surgical patients. Monitoring of the
      vesicoelastic properties of blood using rotational thromboelastometry and
      thromboelsatography (TEG) has been a major step towards ameliorating the risks
      associated with these 2 evils by providing trageted goal-directed blood product
      resuscitation. Point of care ROTEM and TEG overcome many of the current
      limitatons of conventional laboratory coagulation testing. Despite the peaking
      interest and widespread use there is a lack of consensus whetehr the use of these
      devices to guide blood product resucistation is associated with a reduction in
      mortality. Also, both ROTEM and TEG suffer from some limitations resulting in a
      lack of agreement on the duperiority of one device versus the other. In this
      concise review we discuss the operational charecteristics of both devices and the
      pro-side of the use of ROTEM in cardiac surgery backed with the most recent
      evidence.

PMID- 28758554
TI  - Neurogenic obesity and systemic inflammation following spinal cord injury: A
      review.
AB  - CONTENT: Spinal Cord Injury (SCI) results in physiological changes that markedly
      reduces whole-body metabolism, resulting in neurogenic obesity via adipose tissue
      accumulation. Adipose tissue has been implicated in the release of
      proinflammatory adipokines that lead to chronic, systemic inflammation, and
      evidence suggests these adipokines contribute to the pathogeneses of metabolic
      diseases that often accompany obesity. In this review, we propose the concept of
      neurogenic obesity through paralysis-induced adiposity as the primary source of
      systemic inflammation and metabolic dysfunction reported in chronic SCI. We also
      briefly discuss how exercise in SCI can attenuate the negative consequences of
      obesity-induced inflammation and its comorbidities. METHODS: A MEDLINE, PubMed,
      Google Scholar, and ClinicalKey search was performed using the following search
      terms: obesity, adiposity, adipose tissue, proinflammatory adipokines,
      proinflammatory cytokines, metabolic dysfunction, exercise, physical activity,
      and spinal cord injury. All papers identified were full-text, English language
      papers. The reference list of identified papers was also searched for additional
      papers. RESULTS: Research suggests that obesity in SCI results in a state of
      chronic, systemic inflammation primarily through proinflammatory adipokines
      secreted from excess adipose tissue. The reduction of adipose tissue through the
      use of diet and exercise demonstrates promise to combat neurogenic obesity,
      inflammation, and cardiometabolic dysfunction in SCI. CONCLUSION: Proinflammatory
      adipokines may serve as biomarkers for the development of obesity-related
      complication in SCI. Mechanistic and interventional studies on neurogenic obesity
      induced inflammation in chronic SCI are warranted.

PMID- 28758558
TI  - Acute DeBakey Type I Dissection Repair Using Frozen Elephant Trunk: The Cleveland
      Clinic Technique.
AB  - Over the past 3 decades, the standard surgical management for acute DeBakey type
      I aortic dissection has not significantly changed. Most patients undergo
      ascending aortic replacement with an interposition graft under hypothermic
      circulatory arrest with selective root replacement. Nevertheless, with the
      improvement in overall patient care, acute surgical outcomes continue to improve.
      The frozen elephant trunk (FET) technique was introduced as a modification to
      conventional elephant trunk to treat extensive degenerative and chronic
      dissecting aneurysms involving the aortic arch and the proximal descending aorta.
      The FET technique converts the conventional elephant trunk procedure-an
      inherently 2-stage operation-into a 1-stage repair in selected patients and
      greatly facilitates more distal aortic repair, for others. The surgical strategy
      is tailored to address individual pathology, based on each patient's aortic
      anatomy and disease. FET technique in acute DeBakey type I aortic dissection
      extends the surgical repair into and beyond the arch with the potential to
      address some of the limitations of the conventional type I aortic dissection
      repair, but it has not been widely adopted yet. Only a limited number of
      institutions have embraced this modality during the acute phase of aortic
      dissection out of concern that it may be too complicated during an emergency
      situation. We have developed a simplified technique that has evolved over the
      past several years and the purpose of this report is to describe it.

PMID- 28758559
TI  - Small-for-Size Syndrome: Bridging the Gap Between Liver Transplantation and Graft
      Recovery.
AB  - In living donor liver transplantation, optimal graft size is estimated from
      values like graft volume/standard liver volume and graft/recipient body weight
      ratio but the final functional hepatic mass is influenced by other donor and
      recipient factors. Grafts with insufficient functional hepatic mass can produce a
      life-threatening condition with rapidly progressive liver failure called small
      for-size syndrome (SFSS). Diagnosis of SFSS requires careful surveillance for
      signs of inadequate hepatocellular function, residual portal hypertension, and
      systemic inflammation that suggest rapidly progressive liver failure. Early
      diagnosis, symptom control, and addressing the cause of SFSS may prevent the need
      for retransplantation. With increased attention to avoiding donor risk,
      intensivists will be confronted with more SFSS recipients. In this review, we aim
      to outline a systematic approach to the medical management of patients with SFSS
      by providing a concise synopsis of general supportive care-neurological,
      cardiovascular, and renal support, mechanical ventilation, nutritional support,
      infection control, and tailored immunosuppression-with an aim to avoid end-organ
      damage or death and a review of current interventions including liver support
      devices, portal flow modulating drugs, and other experimental interventions that
      aim to preserve existing hepatic mass and improve conditions for hepatic
      regeneration. We examine evidence for SFSS interventions to provide the reader
      with information that may assist in clinical decision making. Points of
      controversy in care are purposefully highlighted to identify areas where
      additional experimental work is still needed. A full understanding of the
      pathophysiology of SFSS and measures to support liver regeneration will guide
      effective management.

PMID- 28758560
TI  - Facing the Ever-Changing Challenges of Caring for Cardiothoracic and Transplant
      Surgery Patients.

PMID- 28758561
TI  - Troubles After Swan-Ganz Catheter Placement in Cardiac Surgery.

PMID- 28758562
TI  - Thromboelastrography (TEG) Is Still Relevant in the 21st Century as a Point-of
      Care Test for Monitoring Coagulation Status in the Cardiac Surgical Suite.
AB  - Since their introduction into clinical practice in the early 1960s, viscoelastic
      point-of-care (POC) testing-thromboelastrography (TEG) and thromboelastrometry
      (ROTEM)-has become increasingly popular in intensive care units, operating rooms,
      and emergency room settings. As TEG has been an established POC viscoelastic
      testing modality for many years, there has been more research and analysis of its
      utility and ability to reduce transfusions in the general, cardiac, and liver
      surgical sectors compared with ROTEM. The role of TEG versus ROTEM has been
      greatly disputed, although both continue to be utilized in the cardiac suite to
      guide transfusion in cardiac surgery as these procedures produce a profoundly
      different form of bleeding compared to other surgical interventions.

PMID- 28758563
TI  - Papillary Fibroelastoma Found With Transesophageal Echocardiography After a
      Normal Transthoracic Echocardiography.
AB  - We present the case of a patient with transient ischemic attacks who was being
      investigated for multiple embolic strokes. Initial workup, including brain
      computed tomography, computed tomography angiography, and transthoracic
      echocardiography (TTE) were negative for a source until transesophageal
      echocardiography (TEE) found a mass in the left atrium. The TEE differentiated
      the mass as a rare cardiac papillary fibroelastoma on the left atrial free wall
      confirmed by postsurgical pathology. This case highlights the importance of TEE
      as a diagnostic tool for its ability to more accurately differentiate and
      characterize the tumor compared with TTE. This case underscores that a negative
      TTE does not equate to zero risk of the presence of a cardiac tumor. It is
      prudent for the clinician to be cognizant that it may be beneficial to perform a
      TEE even with a negative TTE workup.

PMID- 28758564
TI  - Do medical residents perform patient-centered medical home tasks? A mixed-methods
      study.
AB  - BACKGROUND: Increasingly, residents are being trained in Patient-centered Medical
      Home (PCMH) settings. A set of PCMH entrustable professional activities (EPAs)
      for residents has been defined but not evaluated in practice. OBJECTIVE: To
      understand whether residents trained at PCMH sites reported higher likelihood of
      engaging in PCMH tasks than those training in non-PCMH sites. DESIGN: Survey and
      nominal group data from post-graduate trainees at three residency programs.
      RESULTS: A total of 179 residents responded (80% response). Over half (52%) cared
      for patients at PCMH sites. Residents at PCMH sites were more likely to report
      engaging in tasks in the NCQA domains of enhancing access and continuity (p <
      0.01 for 4/11 tasks), planning and managing care (p < 0.01 for 3/4 tasks),
      providing self-care and community support (p < 0.01 for 3/5 tasks), and
      identifying and managing patient populations (p < 0.01 for 1/6 tasks), but were
      not more likely to report tracking and coordinating care or measuring and
      improving performance. Residents at PCMH sites were more likely to report working
      with medical assistants (p < 0.01), but not other healthcare professionals.
      Qualitative data showed staff teamwork and continuity of care as facilitators of
      patient-centered care, and technological problems and office inefficiencies as
      barriers to care. CONCLUSIONS: Residents trained at PCMH sites were more likely
      to engage in tasks in several NCQA domains, but not care coordination and quality
      assessment. Similar facilitators and barriers to trainee provision of patient
      centered care were cited regardless of PCMH status. Curricula on PCMH principles
      and workflows that foster continuity and communication may help to inform
      residents on PCMH tenets and incorporate residents into team-based care.
      ABBREVIATIONS: EPA: Entrustable professional activity; GIM: General Internal
      Medicine; NCQA: National Center for Quality Assurance; PCMH: Patient-centered
      medical home.

PMID- 28758565
TI  - Lysosomal responses to different gold forms (nanoparticles, aqueous, bulk) in
      mussel digestive cells: a trade-off between the toxicity of the capping agent and
      form, size and exposure concentration.
AB  - Gold nanoparticles (NPs) are increasingly used in technological materials and
      consumer products and may have toxicological characteristics distinct from bulk
      and aqueous gold. The aim of this work was to understand the effects of Au NPs
      especially, how the form, the size and the coating influence
      bioaccumulation/biodistribution and toxicity of NPs in mussels, Mytilus
      galloprovincialis. Mussels were exposed for 3 d to concentrations of Au (0.75, 75
      and 750 MUg Au/l) supplied as Au-Cit NPs (5 and 40 nm; Au5-Cit and Au40-Cit),
      bulk and aqueous Au (HAu(III)Cl4), and to the capping agent (Na-citrate) in doses
      used in the formulation of NPs (0.005, 0.5, 5 mg/l). Citrate-stabilised NPs
      formed stable suspensions of aggregates in seawater (SW) available for mussels.
      Au accumulation in soft tissues was similar in Au40-Cit and aqueous Au exposed
      mussels, lower in Au5-Cit and negligible after bulk exposure. Au NPs were
      identified (X-ray microanalysis) in different compartments of the endolysosomal
      system in digestive cells, and small size NPs (5 nm) were more accumulated than
      40 nm NPs, aqueous and bulk. The degree of lysosomal membrane destabilisation was
      related with intralysosomal metal accumulation and depended on the form, NP size
      (Au5-Cit > Au40-Cit > aqueous > bulk) and concentration. Citrate alone provoked
      extreme reduction in lysosomal membrane stability. Toxicopathic alterations were
      recorded in digestive gland cells (vacuolisation, swollen RER, connective tissue
      disruption and cell death) especially in mussels exposed to 40 nm NPs.
      Deleterious effects resulted from digestive tract obliteration (agglomerates) and
      digestion malfunction. The toxic effect of Au-Cit NPs was influenced both by NP
      size, capping agent composition and the dose of capping agent carried by NPs,
      which was size dependent.

PMID- 28758566
TI  - The influence of level of spinal cord injury on adipose tissue and its
      relationship to inflammatory adipokines and cardiometabolic profiles.
AB  - OBJECTIVE: Level of injury (LOI) and the role of adipose tissue and its
      proinflammatory adipokines in cardiometabolic dysfunction following spinal cord
      injury (SCI) remains poorly understood. We aim to examine the influence of LOI on
      adipose tissue and its relationship to proinflammatory adipokines and
      cardiometabolic profiles following SCI. DESIGN: Cross sectional and correlational
      study. SETTING: Clinical hospital and academic setting. PARTICIPANTS: Forty-seven
      individuals with chronic motor complete SCI (age 43.8+/-11.5 y, BMI: 27.3+/-5.3)
      were classified as having tetraplegia (TSCI; n=12) or paraplegia (PSCI; n=35).
      INTERVENTION: Non applicable. OUTCOME MEASURES: Visceral (VAT) and subcutaneous
      (SAT) adipose tissue volumes were measured using magnetic resonance imaging.
      Proinflammatory adipokines (tumor neurosis factor-alpha, interleukin-6 (IL-6),
      plasminogen activatable inhibitor-1, thrombin-activatable fibrinolysis inhibitor,
      and high-sensitivity c-reactive protein) and cardiovascular, carbohydrate, and
      lipid profiles were assessed according to standard techniques. RESULTS: VAT
      volume was greater in TSCI versus PSCI (p=0.042); however, after covarying for
      age this significance was lost (p>0.05). IL-6 was significantly elevated in TSCI
      (p<0.05), while other markers of inflammation generally were elevated, but did
      not reach statistical significance (p>0.05). Systolic blood pressure and total
      cholesterol were significantly lower in TSCI (p<0.05), while fasting glucose was
      significantly lower in PSCI (p<0.05). A number of proinflammatory adipokines and
      cardiometabolic markers significantly correlated with adipose tissue depots by
      LOI (p<0.05). CONCLUSION: The results show that LOI does not influence the
      distribution of adipose tissue, but does influence proinflammatory adipokines and
      cardiometabolic profiles following SCI. Further research is needed to evaluate
      impact of lean body mass on these findings.

PMID- 28758567
TI  - The Benefit of a Visually Guided Beamformer in a Dynamic Speech Task.
AB  - The aim of this study was to evaluate the performance of a visually guided
      hearing aid (VGHA) under conditions designed to capture some aspects of "real
      world" communication settings. The VGHA uses eye gaze to steer the acoustic look
      direction of a highly directional beamforming microphone array. Although the VGHA
      has been shown to enhance speech intelligibility for fixed-location, frontal
      targets, it is currently not known whether these benefits persist in the face of
      frequent changes in location of the target talker that are typical of
      conversational turn-taking. Participants were 14 young adults, 7 with normal
      hearing and 7 with bilateral sensorineural hearing impairment. Target stimuli
      were sequences of 12 question-answer pairs that were embedded in a mixture of
      competing conversations. The participant's task was to respond via a key press
      after each answer indicating whether it was correct or not. Spatialization of the
      stimuli and microphone array processing were done offline using recorded impulse
      responses, before presentation over headphones. The look direction of the array
      was steered according to the eye movements of the participant as they followed a
      visual cue presented on a widescreen monitor. Performance was compared for a
      "dynamic" condition in which the target stimulus moved between three locations,
      and a "fixed" condition with a single target location. The benefits of the VGHA
      over natural binaural listening observed in the fixed condition were reduced in
      the dynamic condition, largely because visual fixation was less accurate.

PMID- 28758568
TI  - Mother-to-child HIV-transmission prevention programs in a sub-Saharan African
      setting: The Gabonese experience.
AB  - In many developing countries, mothers' awareness remains a challenge despite the
      scaling up of antenatal care and programs preventing mother-to-child (MTC) HIV
      transmission. The present study was done in Libreville, Gabon where all antenatal
      care (delivery included) is free of charge. Here we assessed the timing of
      antenatal antiretroviral (ARV) prophylaxis initiation, HIV-exposed infants' age
      at their first postnatal HIV check visit and investigated the association between
      mothers' awareness or knowledge on their ARV therapy and infants' HIV infection.
      We interviewed HIV-positive mothers on their first and subsequent laboratory
      visits to investigate infants' HIV status and tested infants for HIV RNA and
      antibody between 2012 and 2014. We established that (1) of 718 HIV-positive
      mothers, only 6% were fully aware and knew what ARV treatment they were on during
      pregnancy; (2) half of the women (54%) start their antenatal ARV prophylaxis
      initiation during the second trimester of pregnancy; (3) 64% of HIV-exposed
      infants had their first HIV infection screening between birth and three months of
      age; (4) the overall prevalence of HIV infection in infants born from infected
      mothers was 8.9%; and (5) infants born from mothers uncertain about taking
      prophylactic ARV therapy were 13.3 times more likely to be infected by HIV than
      infants born from mothers certain about taking prophylactic ARV therapy. In
      conclusion, the study showed that despite free antenatal care, early access and
      adherence to components of MTC, HIV transmission preventive care remains
      unsatisfactory.

PMID- 28758569
TI  - Association between self-reported sexually transmitted infection treatment and
      mental health symptoms in conflict-affected eastern Democratic Republic of the
      Congo.
AB  - Although poor mental health has been associated with sexual risk behavior, few
      studies have examined the association between mental health and sexually
      transmitted infections (STIs) in conflict-affected settings. With elevated
      symptoms of poor mental health in conflict-affected settings, it is important to
      consider if and how mental health may be a risk factor for STIs in these
      settings. We used cross-sectional logistic regression to examine the association
      between symptoms of depression, anxiety, and post-traumatic stress disorder
      (PTSD) with having been treated for an STI in rural South Kivu, Democratic
      Republic of the Congo. Among 753 adults, those with elevated self-reported
      symptoms of depression and anxiety (adjusted OR = 2.73, 95% CI 1.68, 4.44) and
      PTSD (adjusted OR = 1.89, 95% CI 1.17, 3.06) had higher odds of reporting ever
      being treated for an STI than those who were not symptomatic. Our findings
      suggest that future studies are needed to more rigorously examine the
      relationship between mental health and STIs.

PMID- 28758570
TI  - Optimization of combined in-vessel composting process and chemical oxidation for
      remediation of bottom sludge of crude oil storage tanks.
AB  - In this research, removal of petroleum hydrocarbons from oily sludge of crude oil
      storage tanks was investigated under the optimized conditions of in-vessel
      composting process and chemical oxidation with H2O2 and Fenton. After determining
      the optimum conditions, the sludge was pre-treated with the optimum state of the
      oxidation process. Then, the determined optimum ratios of the sludge to immature
      compost were composted at a C:N:P ratio of 100:5:1 and moisture content of 55%
      for a period of 10 weeks. Finally, both pre-treated and composted mixtures were
      again oxidized with the optimum conditions of the oxidants. Results showed that
      total petroleum hydrocarbons (TPH) removal of the 1:8 and 1:10 composting
      reactors which were pre-treated with H2O2 were 88.34% and 90.4%, respectively. In
      addition, reduction of TPH in 1:8 and 1:10 composting reactors which were pre
      treated with Fenton were 83.90% and 84.40%, respectively. Without applying the
      pre-treatment step, the composting reactors had a removal rate of about 80%.
      Therefore, pre-treatment of the reactors increased the TPH removal. However, post
      oxidation of both pre-treated and composted mixtures reduced only 13-16% of TPH.
      Based on the results, remarkable overall removal of TPH (about 99%) was achieved
      by using chemical oxidation and subsequent composting process. The study showed
      that chemical oxidation with H2O2 followed by in-vessel composting is a viable
      choice for the remediation of the sludge.

PMID- 28758571
TI  - Experimental simulation and fuzzy modelling of landfill biogas production from
      low-biodegradable MBT waste under leachate recirculation.
AB  - In the perspective of a sustainable waste management, biodegradable waste
      destined to landfilling should be reduced. This work aims to study a combination
      of waste pretreatments and leachate recirculation. A lab-scale experiment and
      fuzzy-modelling were chosen to predict cumulative methane production from low
      biodegradable waste (LBW) under leachate recirculation. Thanks to moisture
      increase, the degradation of LBW was reactivated and the cumulative methane
      production reached 28 NL CH4 kg-1 after 442 days. The organic fraction was
      stabilized with a final chemical oxygen demand (COD) of 81 mg L-1. Fuzzy model
      was proposed as an alternative to the common deterministic models, affected by
      high uncertainties. Eleven inputs (pH, Redox potential, COD, volatile fatty
      acids, ammonium content, age, temperature, moisture content, organic fraction
      concentration, particle size and recirculation flow rate) were identified as
      antecedent, and two outputs, or consequents, were chosen: methane production rate
      and methane fraction in biogas. Antecedents and consequents were linked by 84 IF
      THEN rules in a linguistic form. The model was also tested on six literature
      studies chosen to test different operational conditions and waste qualities. The
      model outputs fitted the experimental data reasonably well, confirming the
      potential use of fuzzy macro-approach to model sustainable landfilling.

PMID- 28758572
TI  - The interatrial septal aneurysm as a diagnostic aid in pulmonary embolism.

PMID- 28758573
TI  - Shrinking lung syndrome in systemic lupus erythematosus: a single-centre
      experience.
AB  - Introduction Shrinking lung syndrome (SLS) is a rare manifestation of systemic
      lupus erythematosus (SLE), characterized by decreased lung volumes and extra
      pulmonary restriction. The aim of this study was to describe the characteristics
      of SLS in our lupus cohort with emphasis on prevalence, presentation, treatment
      and outcomes. Patients and methods Patients attending the Toronto Lupus Clinic
      since 1980 ( n = 1439) and who had pulmonary function tests (PFTs) performed
      during follow-up were enrolled ( n = 278). PFT records were reviewed to
      characterize the pattern of pulmonary disease. SLS definition was based on a
      restrictive ventilatory defect with normal or slightly reduced corrected
      diffusing lung capacity for carbon monoxide (DLCO) in the presence of suggestive
      clinical (dyspnea, chest pain) and radiological (elevated diaphragm)
      manifestations. Data on clinical symptoms, functional abnormalities, imaging,
      treatment and outcomes were extracted in a dedicated data retrieval form. Results
      Twenty-two patients (20 females) were identified with SLS for a prevalence of
      1.53%. Their mean age was 29.5 +/- 13.3 years at SLE and 35.7 +/- 14.6 years at
      SLS diagnosis. Main clinical manifestations included dyspnea (21/22, 95.5%) and
      pleuritic chest pain (20/22, 90.9%). PFTs were available in 20 patients; 16 (80%)
      had decreased maximal inspiratory (MIP) and/or expiratory pressure (MEP).
      Elevated hemidiaphragm was demonstrated in 12 patients (60%). Treatment with
      prednisone and/or immunosuppressives led to clinical improvement in 19/20 cases
      (95%), while spirometrical improvement was observed in 14/16 patients and was
      mostly partial. Conclusions SLS prevalence in SLE was 1.53%. Treatment with
      glucocorticosteroids and immunosuppressives was generally effective. However, a
      chronic restrictive ventilatory defect usually persisted.

PMID- 28758574
TI  - Personalized & Precision Medicine in Cancer: A Theranostic Approach.
AB  - BACKGROUND AND OBJECTIVES: There are many challenges in the execution of targeted
      therapy in cancer due to tumor heterogeneity between individuals. In case of
      solid tumors this is one of the reasons as to why genomic analysis from single
      tumor biopsy specimens underestimate the mutational burdens in such heterogeneous
      tumors thus contributing to treatment failure and drug resistance. Molecular
      characteristics redefine tumor classification for molecular targeted therapies
      ensuring the best patient specific therapies with better specificity and cost
      effective ratio. Functional imaging like Positron Emission Tomography & Computed
      Tomography (PET-CT) with 18-F Fluorodeoxyglucose (FDG) has been extensively used
      in oncology to assess the glucose metabolism in tumor cells since long. It has
      been further redefined to use other radiopharmaceutical targets capable of tumor
      characterization, microenvironment, angiogenesis, proliferation, apoptosis,
      receptor expression and few others. Among these the receptor expression in tumors
      have been studied in detail and specific imaging probes have been developed for
      imaging with either Single Photon Emission Computed Tomography (SPECT-CT) or PET
      CT. Combination of these diagnostic tool with the same vector has permitted an
      easy switch from diagnosis to therapy using a therapeutic radionuclide when such
      expression is documented. Thus in Nuclear Medicine the concept of Theranostics
      have been utilized with ease and successfully implemented the theranostic concept
      and has become a valid example of personalized and precision medicine. Imaging
      and therapy of thyroid cancer, neuroendocrine tumors and castration resistant
      prostate cancer are current examples of this concept. CONCLUSION: Molecular
      imaging has high potential to link target identification with therapy and thus to
      personalize it. It also has a very high potential for in-vivo tissue
      characterization, to improve prediction, prognostication, road map for biopsy and
      monitoring of therapy.

PMID- 28758575
TI  - Biological Activities and Secondary Metabolite Screening of Rumex hastatus
      Extract through Fourier Transform Infrared and Raman Spectroscopy.
AB  - BACKGROUND: Human infectious diseases are caused by various pathogens including
      bacteria, fungi, viruses, parasites, and protozoans. These infectious agents are
      controlled by using synthetic drugs as well as natural sources. OBJECTIVE: The
      aim of current study was to evaluate the antibacterial effect of Rumex hastatus
      against clinical bacterial pathogens. METHODS: In current research antibacterial
      effect of Rumex hastatus was analyzed against seven clinical pathogenic bacteria
      such as Escherichia coli, Serratia marcescens, Streptococcus pyogenes,
      Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella pneumoniae and
      Pseudomonas aeruginosa through agar well diffusion method. The boiled extract was
      used for the phytochemical screening, antioxidant potential, thin layer
      chromatography, bio-autography, and spot screening. Genomic DNA was extracted to
      find the DNA protection effect of R. hastatus. RESULTS: Antibacterial results
      showed that diethyl ether extract has the maximum inhibition of S. pyogenes (9.66
      +/- 0.57 mm). Acetone and diethyl ether extracts showed moderate inhibition of K.
      pneumoniae (6.33 +/- 1.52 mm and 5.66 +/-1.15 mm) and S. aureus (6.33 +/- 1.52 mm
      and 5.66 +/- 0.57 mm). Similarly, chloroform extract indicated moderate
      inhibition of S. pyogenes (5.66 +/- 1.15 mm). Ethanol extract had low or even no
      effect on the growth of bacteria. Genomic DNA extraction also encouraged the
      antibacterial effect of R. hastatus. Various phytochemical constituents such as
      ketoses, oligosaccharides, amino acids, amines, sugars, flavonoids, and
      antioxidant constituents were detected. TLC-Bioautography and spot screening
      results revealed the potential use of R. hustatus as an antibacterial agent.
      CONCLUSION: It was concluded that most of the tested fractions appeared as an
      important source for the discovery of new antimicrobial drugs.

PMID- 28758576
TI  - Ultrasound Assisted One-pot and Sequential Synthesis of 3-methylene-isoindolin-1
      ones and their in vitro Evaluation.
AB  - BACKGROUND: 3-Methyleneisoindolin-1-one derivatives containing a pyridin-2
      ylmethyl substituent on their ring nitrogen were designed as potential bioactive
      agents. A one-pot synthesis of these compounds was achieved via sequential C-C
      coupling, followed by C-Si bond cleavage and subsequent tandem C-C/C-N bond
      forming reaction under ultrasound irradiation. METHOD: The methodology involved
      coupling of (trimethylsilyl)acetylene with iodoarenes in the presence of 10% Pd/C
      CuI-PPh3-Et3N in MeOH followed by treating the reaction mixture with K2CO3 in
      aqueous MeOH, and finally coupling with 2-iodo-N-(pyridin-2-ylmethyl)benzamide.
      The in vitro evaluation of these compounds was performed to identify some initial
      hit molecules one of which showed dose dependent inhibition of PDE4B.

PMID- 28758577
TI  - Translational Shift of HSP90 as a Novel Therapeutic Target from Cancer to
      Neurodegenerative Disorders: An Emerging Trend in the Cure of Alzheimer's and
      Parkinson's Diseases.
AB  - BACKGROUND: Despite having extensive research, the apparent pathogenic mechanism
      of Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative
      diseases (NDs) have not yet fully understood. The Heat Shock Protein 90 (HSP90),
      a ubiquitous molecular chaperone, found to have an important role in averting
      protein misfolding and aggregation through inhibition of apoptotic activity in
      neuro-inflammatory diseases. Various researchers have confirmed its role in
      maintaining aberrant neuronal protein's functional stability to a great capacity.
      It is also involved in regulating the activity of the heat shock factor-1 (HSF
      1), a vital regulator of the heat shock response mechanism that cells employ to
      protect themselves against stress conditions. This quality makes the HSP90 an
      ideal candidate for novel inhibitory target for therapeutic modality in NDs.
      METHODS: An extensive literature search was conducted for relevant studies on
      PubMed, ScienceDirect, Springer- Link etc. The articles were carefully read in
      their entirety to determine whether they contained information on the topic of
      interest. Additionally, the reference sections of these articles were searched
      manually to get more relevant and eligible studies. RESULTS: We have taken an
      attempt to reveal how HSP90 play important roles with key neuronal proteins
      involved in supporting the AD and PD pathology. We have further on structure
      function relationship of HSP90 to understand its efficacy as a new target in AD
      and PD by utilizing new generation of HSP90 inhibitors such as geldanamycin and
      its derivatives, 17-AAG, 17-DMAG, IPI-504, radicicol and its derivatives. HSP90
      inhibition leads to suppress atypical neuronal activity by assisting in improving
      protein aggregation and its related toxicity. Further, the formation of neuronal
      aggregates is also influenced by HSP90 inhibitors and provides protection from
      toxicity of protein through HSF-1 activation and HSP70 induction in AD.
      CONCLUSION: HSP90 inhibition has emerged as a potential target in treating
      diverse array of diseases especially NDs. In spite of a large amount of research
      in this direction, the clear cut molecular mechanisms of HSPs associated with
      neuroprotection are still poorly elucidated and hence more focus is needed toward
      HSPs and its inhibitory mechanism. The development of HSP90 inhibitors that
      induce heat-shock response without cytotoxicity for treatment of NDs are still in
      its early stage. A panel of novel designed research and clinical trial studies
      are greatly needed to establish the therapeutic reliability and efficacy of HSPs
      in order to provide best cure for NDs.

PMID- 28758578
TI  - Advances in the Use of Multifunctional Mesoporous Silica Nanoparticles and
      Related Nanomaterials as Carriers for the Cancer Treatment.
AB  - BACKGROUND: In recent years, there has been an unprecedented expansion in the
      field of nanomedicine with the development of new nanoparticles for the diagnosis
      and treatment of cancer. It is also known that the use of nanocarriers as drug
      delivery systems for therapeutic or imaging agents can improve the
      pharmacological properties of ordinarily used compounds in cancer diagnosis and
      treatment. OBJECTIVE: Advances in the surface regulating of nanoparticles to
      accommodate targeting ligands turned nanocarriers attractive candidates for
      future impact involving targeted drug delivery. Although not targeted, several
      nanocarriers have been approved for clinical use and they are currently used to
      treat or diagnose various kinds of cancers. Furthermore, there are several
      formulations, which are now in various stages of clinical trials than also can
      combine with thermal treatment. CONCLUSION: This review examined some mesoporous
      silica nanoparticles and related nanomaterials and discussed the advantages of
      using nanocarriers in cancer therapy.

PMID- 28758579
TI  - Perspectives of Medieval Persian Medicine on Multiple Sclerosis.
AB  - INTRODUCTION: Traditional Persian Medicine (TPM) was the prevailing practice of
      medicine in the Eurasia region up through the 18th century, a practice of
      medicine stemming back to Hippocrates and to the 5000 year old civilization of
      the region. It is a school of medicine which touches on many a delicate points
      which may seem unimaginable within the realm of modern allopathic medicine. This
      practice of ancient medicine besides shedding light on various possible
      theoretical modern day disorders serves as a vast resource for therapeutics. In
      this paper, we present study of the manuscripts of this ancient medical practice
      in search of symptom presentations coinciding with presentation of multiple
      sclerosis (MS). MATERIAL & METHOD: This paper represents a comprehensive search
      through TPM texts and manuscripts with the intention to seek possible clues on MS
      from potentially valuable age-old resources. We predominantly focused our search
      on the works of five eminent physicians of Medieval Persia: Avicenna (980-1037
      AD), Haly Abbas (949-982 AD), Rhazes (865-925 AD), Averroes (1126-1198 AD) and
      Jorjani (1042-1137 AD). RESULTS: In this paper, the authors attempt a theory and
      conclude with high probability that a conjunction of a series of signs, symptoms
      found in TPM texts under the terms khadar, isterkha and falej form the symptoms
      and the disease pattern of modern day MS. This theory draws upon existent
      similarities in terms of disease pathology, disease patterns and predisposing
      factors seen between MS and the related morbidities within Persian Medicine.
      CONCLUSION: We recommend further examinations of such potentially valuable long
      standing resources, examining the diagnoses and treatments as set forth by
      Persian Medicine through international collaboration within the global scientific
      community.

PMID- 28758581
TI  - Implications of PEGylation of Carbon Nanotubes for Central Nervous System
      Bioavailability.
AB  - BACKGROUND AND OBJECTIVE: In this mini-review, we have compiled the most recent
      and comparable information to shed light on the action of PEGylation in the
      biodistribution of carbon nanotubes (CNT) in the central nervous system (CNS). It
      is well known that due to the complexity of the CNS and the severity of the
      outcome following changes in this system, this is one of the areas where there
      are more investments in research to develop new technologies and approaches for
      more effective and less invasive treatments. The CNS is highly protected against
      toxic and invasive microorganisms thanks to the blood brain barrier (BBB), but
      this protection also prevents the passage of potentially beneficial molecules for
      the treatment of neurological disorders. Nanotechnology attempts to develop
      nanocompounds that are biocompatible and non-immunogenic, and that are able to
      cross the BBB in therapeutic amounts without causing damage and to diffuse
      through nerve tissue. These compounds should also be cleared and biodistributed
      properly, being capable of performing drug delivery exclusively for CNS
      pathologies, such as neurodegenerative diseases (Parkinson's and Alzheimer's) and
      brain tumors. CONCLUSION: In this way, this review focuses on CNT PEGylation,
      aiming to help in the development of viable and effective nanomedicines for
      neuroscience applications.

PMID- 28758580
TI  - Chromosomal Micro-aberration in a Saudi Family with Juvenile Myoclonic Epilepsy.
AB  - BACKGROUND AND OBJECTIVE: Epilepsy is etiologically and genetically complex
      neurological disorder affecting millions of people worldwide. Juvenile myoclonic
      epilepsy (JME) is the most common epilepsy syndrome that starts in the teen age
      group commonly between ages 12, 18, and lasts till adulthood. One out of fourteen
      people with epilepsy suffers with JME. Myoclonic seizures and muscle twitching or
      uncontrolled jerking are the most common type of seizures in the people suffering
      with JME. METHOD: To observe the novel CNVs involved in JME, we investigated a
      Saudi family with nine siblings including one male and one female affected
      members. In this study we used high density whole genome Agilent sure print G3
      Hmn CGH 2x 400K array-CGH chips. Our results showed CNVs including the
      amplifications and deletions in different chromosomal regions in the patients as
      compared to the normal members of the family. Amplifications were observed in the
      chromosome 22 cytoband 22q11.23 with LDL receptor related protein 5 like (LRP5L),
      Immunoglobulin Lambda-Like Polypeptide 3 (IGLL3) and crystallin beta B2
      pseudogene (CRYBB2P) genes respectively whereas the deletions were observed in
      the chromosomal regions 4q22.2 with Glutamate receptor, ionotropic, delta 2
      (GRID2) as potential gene cytoband 1p31.1 with potential Neuronal Growth
      Regulator 1 gene (NEGR1) gene in this region and NME/NM23 family member (NME7)
      gene cytoband 1q24. Moreover, the array CGH resulting in deletions and
      duplication were also validated by using primer for simple PCR or also by using
      quantitative real time PCR analysis. We found deletions and duplication in JME
      patients in our study for the first time in Saudi population. RESULTS &
      CONCLUSION: The findings in this study suggest that the array-CGH may be
      considered as a first line of genetic testing for diagnosis of epilepsy unless
      strong evidence is presented for a monogenic syndrome. The use of high throughput
      technique in this study will help to identify novel mechanisms underlying
      epileptic disorder in order to lower the burden of epilepsy in Saudi Arabia.

PMID- 28758582
TI  - Potential Novel Treatments for Bipolar Depression: Ketamine, Fatty Acids, Anti
      inflammatory Agents, and Probiotics.
AB  - BACKGROUND: Treatments for depression in bipolar disorder (BD) are far less well
      developed than for unipolar major depressive disorder. Several innovative and
      experimental approaches have been emerging recently, including use of the
      dissociative anesthetic ketamine and other antagonists of central NMDA glutamate
      receptors, as well as unsaturated fatty acids, anti-inflammatory agents, and
      possibly probiotic methods. METHOD: We reviewed relevant reports from the past
      decade. FINDINGS: Ketamine, a phencyclidine-like NMDA-glutamate receptor
      antagonist, has emerged as a highly innovative, experimental treatment for
      treatment-resistant unipolar major depression, possibly in bipolar depression,
      and with brief antisuicidal effects. Its limitations include poor
      bioavailability, rapid but short-lived effects, and little information about long
      term benefits and safety of repeated administration. Polyunsaturated fatty acids
      critical for the structure and functioning of neuronal and other cell membranes
      have some evidence of benefit as experimental treatments for depression including
      in BD. There also is evidence of altered expression of peptides associated with
      inflammation in mood disorder patients, encouraging experimental treatment with
      anti-inflammatory agents; of these, the COX-II inhibitor celecoxib has shown some
      evidence of benefit. The concept of altering intestinal flora with probiotic
      treatments to treat mood disorders remains speculative. CONCLUSION: Ketamine
      represents an innovative, rapidly acting, experimental treatment for bipolar
      depression with practical limitations. Unsaturated fatty acids and anti
      inflammatory agents have inconsistent support; probiotic treatments lack
      evidence. These innovative approaches require much more clinical investigation.

PMID- 28758583
TI  - New Trends in the Treatment of Schizophrenia.
AB  - OBJECTIVES: This article are to describe current trends in the treatment of
      schizophrenia and the most interesting new approaches to optimizing outcome and
      fostering the development of new schizophrenia treatments. RESULTS: Increasing
      utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g.
      clozapine- type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist,
      amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with
      additional neurotransmitter targets, is occurring as their advantages in
      efficacy, especially for cognitive impairment and mood symptoms, and side effects
      are becoming appreciated. Typical APDs, e.g. haloperidol, are diminishing in
      favor because of their EPS, especially, tardive dyskinesia (T D) and appreciation
      that reducing D2 receptor stimulation is not the only means to treat psychosis.
      Some of the mechanisms inherent in various AAPDs, e.g. 5-HT2A inverse agonism,
      and D3 receptor partial agonism, are now recognized as effective treatments for
      psychosis. A new focus on treating the cognitive impairment associated with
      schizophrenia (CIAS) has emerged via mechanisms such as stimulation of
      acetyldraline receptor with muscarinic and nicotinic receptor agonists, but
      demonstrating their efficacy in trials is proving elusive. Pharmacogenetic
      strategies which may lead to personalized treatment of schizophrenia are emerging
      but have not yet succeeded in being widely reimbursable. Transcranial stimulation
      and cognitive enhancement therapy are more common but more evidence for their
      efficacy is needed. CONCLUSION: The heterogeneity of the pathophysiology of the
      various domains of schizophrenia requires a diversity of treatments that are best
      met by the expert use of AAPDs at the current time. Pharmacogenetic efforts are
      consistent with new evidence that multiple genes are involved in the risk for
      schizophrenia and the effectiveness of AAPDs.

PMID- 28758584
TI  - Antidepressant Potential of Peptides: New Insights as Future Therapeutic.
AB  - BACKGROUND & OBJECTIVE: Clinical depression is an unsatisfactory mood disorder
      affecting millions of people worldwide. The disorder is associated with a
      phenomenal number of suicidal attempts each year, and it has been estimated that
      10-20 million people around the world made an attempt of suicide in some stage of
      the disease. Thus, medicinal intervention is ultimately required to avoid such
      type of extreme outcomes. There are numerous therapeutic antidepressant options
      in clinical practice, however, most of them face the challenge of efficacy, side
      effects, and patient compliance. In this scenario, new effective and safe
      therapeutic agents are becoming the major focus of researchers in the area of
      neuropharmacology, who and are evaluating different sources such as synthetic and
      natural therapeutics. Similarly, thousands of peptides have already shown vital
      role in human physiology for regulation of different activities. CONCLUSION: This
      mini-review will focus on peptides with reported antidepressant activity, along
      with their mechanism of action. Furthermore, the present article summarizes the
      literature pertaining to these peptides as antidepressant agents.

PMID- 28758585
TI  - From A Formal Training Program In Musculoskeletal Ultrasound (MSUS) To A High
      Reproducibility for MSUS Ultrasound In Rheumatoid Arthritis.
AB  - OBJECTIVE: To assess the intra- and inter-observer reliability of Ultrasound (US)
      in scoring B-mode, Doppler synovitis and combined B-mode and Doppler synovitis
      scores in different peripheral joints of Rheumatoid Arthritis (RA) patients.
      METHODS: Four rheumatologists with a formal training in Musculoskeletal US
      (MSKUS) particularly focus on definitions and scoring synovitis on B-mode and
      Doppler mode participated in a patient- based reliability exercise on 16 active
      RA patients. The four rheumatologists independently and consecutively performed a
      B-mode and Power Doppler (PD) US assessment of 7 joints of each patient in two
      rounds in a blinded fashion. Each joint was semi quantitatively scored from 0 to
      3 for B-mode Synovitis (BS), Doppler Synovitis (DS), and combined B-mode/Doppler
      synovitis (CS). Intraobserver reliability was assessed by Cohen's kappa.
      Interobserver reliability was assessed by unweight Light's kappa. RESULTS: The
      mean prevalence of synovitis on B-mode was 83% of joints; scores ranging from
      grade 1 in 18% of joints, to grade 3 in 33%. In 55% of joints synovial PD signal
      was detected and the distribution of scores range from 14% of joints for grade 3,
      to 26% for grade 2. After a total of 448 joints scanned with 896 adquired images
      our intraobserver and interobserver reliability was good to excellent for most of
      the joints. CONCLUSION: Formal, structured and continuous training in
      musculoskeletal ultrasound would bring a good to excellent reproducibility in
      rheumatological hands with a high reliability in real time acquisition BS, DS and
      CS modalities for scoring synovitis in patients with active rheumatoid arthritis.

PMID- 28758586
TI  - Effects of the Disease Characteristics and the Treatment on Psychological Status
      in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis.
AB  - INTRODUCTION: Various psychiatric disorders, especially depression and anxiety,
      are seen in 2/3 of the chronic rheumatic diseases with chronic pain. In this
      study, we aimed to define anxiety and depression rates in Rheumatoid Arthritis
      (RA) and Ankylosing Spondylitis (AS) patients (under treatment) with similar age
      and gender; to compare the obtained data with each other and healthy control
      group; and also we aimed to investigate the relationship between human leukocyte
      antigen B27(HLA-B27) in AS, Rheumatoid Factor (RF) and anti-cyclic citrullinated
      peptide antibodies (anti-CCP) in RA with anxiety and depression. METHOD: 46
      patients with RA, 43 patients with AS and 29 healthy volunteers were evaluated
      with Beck Depression Inventory (BAI) and Beck Anxiety Inventory (BAI).
      Participants were also noted for their educational status, occupation status,
      family history of illness, duration of the disease and their current treatments.
      Then we compared the obtained data with the healthy control group. SPSS (IBM
      Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.p=0. Armonk, NY:
      IBM Corp.) was used for performing statistical analysis. RESULTS: There was no
      difference between the groups according to age, sex, duration of illness
      (p=0.104, p=0.767, p=0.377). A significant difference between groups in terms of
      BAI values were determined (p=0.018). In subgroup analyzes, the median BAI value
      of AS group was found to be higher than the control group (p=0.020). There were
      no differences in BAI values between AS and RA groups or between RA and the
      control groups (p>0.05, p>0.05 respectively). Also, there were no differences
      between the groups in terms of BDI values (p=0.055). CONCLUSIONS: Especially,
      chronic pain-related diseases are often associated with mental disorders,
      especially depression and anxiety. As a result, a multidisciplinary approach
      including psychiatric support should be used when planning treatment for these
      patients.

PMID- 28758587
TI  - Atypical form of Adult-onset Still's Disease with Distal Interphalangeal Joints
      Involvement.
AB  - BACKGROUND: A distal interphalangeal (DIP) joint involvement in the adult-onset
      Still's disease (AOSD) has been described in some publications but is rarely
      reported to be severe. We report severe DIP joints damages in a young patient
      with AOSD. CASE REPORT: A 22 years old patient presented to our department
      complaining of inflammatory joints pain associated with prolonged fever and
      cutaneous rash. Physical examination identified polyarthritis and
      hepatosplenomegaly but no lymphadenopathies. After an extensive screening for
      neoplastic, infectious or hematologic diseases, the patient was finally diagnosed
      with AOSD. Treatment based on corticosteroids was then initiated with a good
      response on systemic signs. However, the patient continued to have recurrent
      arthritis affecting wrists and proximal interphalangeal joints. A Few years
      later, he developed a severe and disabling DIP arthritis with signs of joint
      destruction on conventional radiographs and MRI. Despite the initiation of
      methotrexate with optimal dosage, the patient continued to have polyarticular
      flares. The combination of methotrexate and sulfasalazine was responsible for
      drug-induced hepatotoxicity and this treatment was stopped. Anti-TNFalpha
      treatment was then indicated as general signs improved but severe joints damage
      persisted. Unfortunately, and due to healthcare system considerations, the
      patient was not able to benefit from TNFalpha inhibitors, and remained on
      methotrexate treatment only. Conculsion: The distal destructive arthritis during
      AOSD is rare and controversial. Our patient had a severe form with resistance to
      conventional therapies.

PMID- 28758588
TI  - Preface.

PMID- 28758589
TI  - Carbon Nanotubes in the Treatment of Skin Cancers: Safety and Toxicological
      Aspects.
AB  - BACKGROUND: Skin cancer is depicted to be the most common malignant disease
      across the globe that is frequently diagnosed in people bearing light skin. Three
      common forms of skin cancers are squamous cell carcinoma, basal cell carcinoma,
      and malignant melanoma. Treatment of skin cancers comprises of various forms of
      management strategies that can help in curing the disease including the use of
      several therapeutic agents. Though numerous therapies have been explored till
      date to deliver the active therapeutics, nanoparticulate based targeted therapy
      has garnered considerable interest and is a promising approach in treating skin
      cancers. OBJECTIVE: The present review aims to explore a novel nano-sized
      carrier, carbon nanotubes for the delivery of various actives researched for skin
      cancer treatment. The write up traces the pre-clinical and clinical reports on
      carbon nanotubes. The feasibility of the nanoparticulate system has been
      elaborated inclusive of the safety and toxicological aspects of the carrier
      system. CONCLUSION: From the reviewed literature it can be concluded that carbon
      nanotubes are the emerging treatment modality in skin cancers as they offer
      targeted delivery to the cancerous cells, act selectively and provide better
      penetration in the neoplastic cells due to improved permeability and retention
      effect.

PMID- 28758590
TI  - Renin-Angiotensin System in Diabetes.
AB  - The renin-angiotensin system (RAS) has two different axes, the classical one with
      the effector peptide angiotensin II and the new one with the effector peptide
      angiotensin (1-7). Both peptides have been shown to be involved in the
      pathogenesis of diabetes mellitus and its consequences, nephropathy, retinopathy
      and cardiomyopathy in animal models and patients. In diabetes, angiotensin II
      acts mostly deleterious and angiotensin (1-7) protective. In this review we
      summarize the knowledge about the role of the different RAS axes in diabetes
      mellitus and the use of drugs interfering with the RAS in the therapy of the
      disease.

PMID- 28758591
TI  - Brain Angiotensin II Involvement in Chronic Mental Disorders.
AB  - BACKGROUND: The functioning of the central nervous system is complex and it
      implies tight and coordinated interactions among multiple components.
      Neurotransmitters systems imbalance is a hallmark in the central nervous system
      (CNS) disorders. These pathologies profoundly impact the social, cultural, and
      economic perspective worldwide. The etiopathology of CNS illnesses is still
      poorly understood, making their treatment difficult. Brain angiotensin II (Ang
      II), through its AT1 receptors, modulates dopaminergic, glutamatergic and
      GABAergic neurotransmission, which are responsible for movement control,
      cognition, emotions and stress responses. Alterations of these functions,
      concomitant with modified brain reninangiotensin system (RAS) components, have
      been described in CNS pathologies like depression, Parkinson, Alzheimer, and
      schizophrenia. In this sense, altered functionality of angiotensin I converting
      enzyme and AT1 receptors, is associated with augmented susceptibility to the
      occurrence of these pathologies. Moreover, some epidemiological data showed lower
      incidence of Alzheimer disease in hypertensive patients under treatment targeting
      RAS; meanwhile preclinical studies relate RAS with Parkinson and depression.
      Little is known about schizophrenia and RAS; however, Ang II is closely related
      to dopamine and glutamate pathways, which are mainly altered in this pathology.
      CONCLUSION: The available evidences, together with the results obtained by our
      group, open the possibility to postulate brain Ang II as a possible therapeutic
      target to treat the above-mentioned CNS disorders.

PMID- 28758592
TI  - The Angiotensin Converting Enzyme 2 (ACE2), Gut Microbiota, and Cardiovascular
      Health.
AB  - BACKGROUND: The renin-angiotensin system (RAS) is an important enzymatic system
      responsible for the regulation of biological functions, such as the arterial
      pressure, hydroelectrolytic control, vascular vasodilatation/vasoconstriction and
      more recently metabolic functions. OBJECTIVES: The aim of the present review is
      to discuss the associations between the gut microbiome and the renin-angiotensin
      system and the influence of their intimate relationship on the cardiovascular
      health. METHODS: A literature review of the main studies published regarding the
      relationship among the renin-angiotensin system, gut microbiota and
      cardiovascular health was performed. RESULTS: The association between the ACE2
      and gut microbiota has been discussed. It is shown that the ACE2/Ang 1-7 axis
      modulates the immune response, influencing the microbiota composition, and thus
      being one of the causes for some diseases physiophatologies, such as diarrhea and
      intestinal inflammatory disease. CONCLUSION: The association between RAS and gut
      microbiota seems to have a strong influence on the genesis of cardiovascular
      diseases, through direct mechanisms, such as nerve stimulation, or indirectly on
      metabolic parameters, such as weight, adiposity and lipid profile.

PMID- 28758593
TI  - Physical Exercise and ACE2-Angiotensin-(1-7)-Mas Receptor Axis of the Renin
      Angiotensin System.
AB  - BACKGROUND: Many physiological responses of the Renin Angiotensin System (RAS)
      are associated with two opposite pathways: (1) a classical one formed by
      angiotensin-converting enzyme (ACE), Angiotensin II (Ang II) and Angiotensin type
      1 (AT1) receptor, which is associated to vasoconstriction, cell proliferation,
      organ hypertrophy, sodium retention and aldosterone release and (2) a counter
      regulatory or vasodilator pathway comprising angiotensin-converting enzyme 2
      (ACE2), Angiotensin-(1-7) [Ang-(1-7)] and Mas receptor, which is involved in
      vasodilation, antiproliferation, anti-hypertrophy, cardioprotective and
      renoprotective actions. OBJECTIVE: This review aimed to bring up-to-date on the
      interactions between physical exercise and the vasodilator axis of the RAS (ACE2
      Ang-(1-7)-Mas receptor axis). We also investigated the relation of acute and
      chronic exercise with blood pressure regulation and components of the vasodilator
      axis of the RAS. METHODS: We searched studies with animal models and humans in
      PUBMED, LILACS and IBECS. RESULTS: Experimental studies showed that physical
      training can stimulate ACE2-Ang-(1-7)-Mas receptor axis in parallel with the
      inhibition of ACE-Ang II-AT1 receptor pathway. However, up to now, the
      interaction between the counter-regulatory RAS axis and physical training is not
      investigated in humans. CONCLUSION: The activation of ACE2-Ang-(1-7)-Mas receptor
      axis may have a role in the beneficial effects of physical training in
      experimental models. Further studies with humans are necessary.

PMID- 28758594
TI  - Effects of Resveratrol and ACE Inhibitor Enalapril on Glucose and Lipid Profiles
      in Mice.
AB  - BACKGROUND: Lipogenesis is a process that involves the fatty acids synthesis.
      Resveratrol and enalapril have been studied for their beneficial physiological
      properties on the glucose and lipid metabolism. OBJECTIVES: The aim of the
      present study was to evaluate the oral administration of resveratrol and
      enalapril effects on glucose and lipid metabolism, evaluating the white pad
      lipogenesis genes expression in mice. METHODS: Swiss male mice were divided into
      four groups and treated for eight weeks as follows: Standard diet ad libitum
      (G1); Standard diet + Resveratrol (G2); Standard diet + Enalapril (G3); Standard
      diet + Resveratrol + Enalapril (G4), where resveratrol was administered with the
      food and enalapril with the water. Body weight, lipid profile, adiposity,
      glycemic parameters and epididymal adipocytes area were assessed. The expression
      levels of FAS, ACC, PPARgamma and SREBP-1c were assessed by RT-PCR. RESULTS: The
      main findings showed an improvement in the insulin sensitivity and glucose
      tolerance in the group G2 as compared to G1. Similar results were found for the
      fasting glucose levels. Decreased triglycerides were observed in the animals
      treated with resveratrol and enalapril, along with decreased weight of the
      epididymal adipose tissue in the animals of the G2 group. A mild reduction in the
      group G4 as compared to the group G1 was observed. Decreased mRNA expression of
      FAS, ACC and PPARgamma in the G4 group when compared to the G1 group were
      observed. CONCLUSION: In conclusion the resveratrol and enalapril association
      improved the glucose and lipid profiles by modulating the expression of some
      lipogenesis genes, which are critical regulators of metabolic homeostasis.

PMID- 28758595
TI  - Vasodilator Effect of Angiotensin-(1-7) on Vascular Coronary Bed of Rats: Role of
      Mas, ACE and ACE2.
AB  - BACKGROUND: Angiotensin(Ang)-(1-7) is a biologically active member of the
      reninangiotensin system that participates of the regulation of blood pressure.
      Although Ang-(1-7) is able to potentiate the vasodilator effect of bradykinin in
      coronary bed of rats, a direct vasodilator effect of Ang-(1-7) in this vascular
      bed has not been characterized. OBJECTIVES: The aim of this study was to evaluate
      the mechanisms involved in the vasodilator effect of Ang-(1-7) in the vasculature
      of isolated rat hearts perfused according to the Langendorff technique at
      constant flow. METHODS: Isolated hearts, after approximately 30 minutes of
      stabilization, were perfused with Krebs-Ringer solution (KRS) alone (control) or
      KRS containing Ang-(1-7). The participation of the Ang-(1-7) receptor Mas, AT1
      receptor, angiotensin-converting enzyme (ACE) and ACE2 was evaluated perfusing
      hearts with a combination of Ang-(1-7) plus A779, Ang-(1-7) plus losartan, Ang-(1
      7) plus captopril/enalapril and Ang-(1-7) plus DX-600, respectively. RESULTS: Ang
      (1-7) induced a significant decrease in the perfusion pressure, indicating a
      direct vasodilatation action of this peptide in the coronary bed. This effect was
      abolished by A779, captopril, enalapril and DX-600 an ACE2-specific inhibitor.
      However, AT1 blockade did not blunt the Ang-(1-7) effect. No significant changes
      were observed in heart rate, as well as in contractile tension and +/-dT/dt.
      Moreover, immunohistochemical analysis showed the presence of Ang-(1-7) and Mas
      in coronary vessels. CONCLUSION: The Ang-(1-7) concentration used in this study
      was unable to induce changes in the cardiac function since no consistent
      alterations in contraction force and HR were viewed after Ang- (1-7) perfusion.
      In summary, this study showed that Ang-(1-7) induces vasodilation in the coronary
      bed of rats and this effect involves coupling to Mas receptor and interaction
      with ACE and ACE2.

PMID- 28758596
TI  - Effects of Sleeve Gastrectomy on the Metabolic Profile and on the Expression of
      Renin-Angiotensin System in Adipose Tissue of Obese Rats.
AB  - BACKGROUND: Sleeve gastrectomy (SG) has been used as a multipurpose surgical
      procedure for the treatment of obesity. OBJECTIVES: The present study aimed to
      assess the effects of SG on the metabolic and inflammatory profile and renin
      angiotensin system (RAS) expression in the white adipose tissue of male rats with
      obesity induced by a high-fat diet. METHODS: Male Wistar rats were treated with a
      standard diet or high-fat diet and submitted to SG or sham surgery. The glycemic
      and lipid profiles and gene expression of inflammatory markers and RAS components
      in adipose tissue were evaluated. RESULTS: SG led to weight loss, decreased
      adiposity (p < 0.01) and a reduction in plasma glucose (p < 0.05), C-peptide (p <
      0.05), insulin (p < 0.001) and total cholesterol (p < 0.05) levels. In addition,
      SG led to a decrease in the expression of tumor necrosis factor-alpha (TNF-alpha)
      (p < 0.01), interleukin- 6 (IL-6) (p < 0.001), angiotensinogen (AGT) (p < 0.001)
      and angiotensin converting enzyme (ACE) (p < 0.05) and increased the expression
      of angiotensin converting enzyme 2 (ACE2) (p < 0.05) in white adipose tissue. No
      statistically significant differences were observed for AT1 (p = 0.10) and Mas (p
      = 0.22) receptors. CONCLUSION: This study showed that SG leads to weight loss and
      improves metabolic parameters. Changes in the expression of RAS components and of
      inflammatory molecules in adipose tissue seem to play a role the before
      beneficial effects of the SG.

PMID- 28758597
TI  - Preterm Birth and Renin-Angiotensin-Aldosterone System: Evidences of Activation
      and Impact on Chronic Cardiovascular Disease Risks.
AB  - Preterm birth (< 37 gestational weeks) reaches 10% of total births worldwide.
      Early exposure to an ex utero environment can alter organogenesis and maturation
      in the newborn. This early onset of events can further promote long-term
      developmental alterations and cardiovascular disease risks. Mechanisms activated
      during preterm birth and promoting such cardiovascular alterations have just
      recently been investigated. As a major candidate, the renin angiotensin
      aldosterone system (RAAS) can be acutely altered during preterm birth and
      persistently activated in later life. Further, RAAS alterations may occur as
      consequence of kidney and heart immaturity to promote adaptive responses,
      suggesting a dual role of this system on fetal and neonatal organogenesis.
      Furthermore, fetal or neonatal exposure to deleterious stress conditions can
      significantly impact on this dual RAAS role, contributing to the establishment of
      hemodynamic and structural alterations. In this review, clinical and experimental
      findings describing RAAS components and activation in relationship with preterm
      birth are discussed. Further clinical and experimental investigations on RAAS
      activation in the context of preterm birth are needed to better understand this
      dual role of RAAS on early development and on programming of risks to
      cardiovascular diseases.

PMID- 28758598
TI  - Synthetic Peptides Derived from Ribosomal Proteins of Leishmania spp. in
      Mucocutaneous Leishmaniasis: Diagnostic Usefulness.
AB  - BACKGROUND: The serological diagnostic methods currently available for
      mucocutaneous leishmaniasis (MCL) lack specificity when complete parasites are
      used; however, such specificity increases when protein fractions are used.
      Ribosomal proteins have been reported to induce antibodies in animal and humans
      infected with the parasite, making them a worth candidate to assess its diagnosis
      potential. OBJECTIVE: This study was thus aimed at evaluating synthetic peptides
      derived from Leishmania braziliensis ribosomal proteins S25 and S5 as antigen
      candidates for diagnosing MCL by ELISA Methods: It was used 8 and 13 peptides
      derived from ribosomal proteins 25 and S5 respectively as antigens in order to
      detect IgG antibodies by ELISA in people with active MCL, Chagas disease (CH) and
      autoimmune disease (AID). RESULTS: 4 of these 21 peptides (P4, P6, P19 and P21)
      had the greatest sensitivity (21.7%, 13.04%, 20% and 20%, respectively) as well
      as having 95%, 100%, 100% and 82.5% specificity, respectively. CONCLUSION: The
      study revealed the limited usefulness of the peptides being studied as a
      diagnostic tool in the conditions used here, because its low sensitivity, but it
      is worth highlighting that the use of peptides as antigen in the serodiagnosis of
      MCL may overcome the cross reaction presented with other antigens, thus avoiding
      false positives.

PMID- 28758599
TI  - Editorial: Peptide Science at the Chemistry and Biology Interface.

PMID- 28758600
TI  - Current Delivery Strategies to Improve the Target of Cell Penetrating Peptides
      Used for Tumor-Related Therapeutics.
AB  - Cell Penetrating Peptides (CPPs) equipped with a high penetrating ability are
      used as a promising tool to gain access to the cell interior, cross the cell
      membrane and deliver bioactive small or macromolecular cargos into the cytoplasm
      or nucleus. The superiority of wide range of applications, high transport
      efficiency and low biological toxicity make them particularly desirable in
      laboratory or clinical studies. Previous studies have shown that their non
      selectivity and reaction with proteins in plasma hamper their application for
      tumor therapy, which might adversely affect the treatment effect and even induce
      some side effects. However, several recent studies have found that various kinds
      of modifiers of CPPs can effectively increase the target selectivity, reduce
      cytotoxicity to normal cells and produce multiple antitumor functions due to the
      different cleavable bonds which are sensitive to the tumor microenvironment or
      other novel designs. Apparently, these designs of 'smart' CPPs appear to be
      promising in the field of antitumor drug delivery. Here, we review these current
      improved approaches which mainly involve strategies of physical, chemical as well
      as biological pathways and we also explain the possible uptake mechanisms of
      direct penetration, internalization and escape which have been discussed in some
      publications with specific attention. In addition, some possible problems needed
      to be considered in the process of improving CPPs are discussed at the end of
      this review. This study aims to present an overview of the latest progress of
      CPPs, and provides a comprehensive theoretical background and reference guidance
      for future laboratory research and clinical application.

PMID- 28758601
TI  - Application of a Theoretical Model Toward Understanding Continued Food Insecurity
      Post Hurricane Katrina.
AB  - OBJECTIVE: Disaster recovery efforts focus on restoring basic needs to survivors,
      such as food, water, and shelter. However, long after the immediate recovery
      phase is over, some individuals will continue to experience unmet needs. Ongoing
      food insecurity has been identified as a post-disaster problem. There is a
      paucity of information regarding the factors that might place an individual at
      risk for continued food insecurity post disaster. METHODS: Using data from a
      sample (n=737) of households severely impacted by Hurricane Katrina, we estimated
      the associations between food insecurity and structural, physical and mental
      health, and psychosocial factors 5 years after Hurricane Katrina. Logistic
      regression models were fit and odds ratios (OR) and 95% CI estimated. RESULTS:
      Nearly one-quarter of respondents (23%) reported food insecurity 5 years post
      Katrina. Marital/partner status (OR: 0.7, CI: 0.42, 0.99), self-efficacy (OR:
      0.56, CI: 0.37, 0.84), sense of community (OR: 0.7, CI: 0.44, 0.98), and social
      support (OR: 0.59, CI: 0.39, 0.89) lowered the odds of food insecurity and
      explained most of the effects of mental health distress on food insecurity.
      Social support, self-efficacy, and being partnered were protective against food
      insecurity. CONCLUSIONS: Recovery efforts should focus on fostering social
      support networks and increased self-efficacy to improve food insecurity post
      disaster. (Disaster Med Public Health Preparedness. 2018;12:47-56).

PMID- 28758602
TI  - Eustachian tube dysfunction leading to middle-ear pathology in patients on
      chronic mechanical ventilation.
AB  - OBJECTIVE: This study aimed to investigate the prevalence of and risk factors for
      Eustachian tube dysfunction leading to middle-ear pathology in patients on
      chronic mechanical ventilation via tracheostomy tube. METHODS: A total of 40
      patients on chronic ventilation were included in a prospective cohort study.
      Middle-ear status was determined by tympanometry. Tympanograms were categorised
      as types A, B or C; types B and C were defined as middle-ear pathology. RESULTS:
      In all, 57 ears of 40 patients were examined. Disease was found in at least 1 ear
      in 26 out of 40 patients. Middle-ear pathology was found in 25 out of 34 patients
      who were tube fed (via nasogastric tube or percutaneous endoscopic gastrostomy)
      vs 1 patient out of the 6 fed orally (p = 0.014), and in 23 out of 31 with
      conscious or cognitive impairment vs 3 out of 9 cognitively intact patients (p =
      0.044). CONCLUSION: Middle-ear pathology is common in patients on chronic
      mechanical ventilation via tracheostomy tube. The highest prevalence was in those
      with impaired consciousness or cognition, and oral feeding appeared protective.

PMID- 28758603
TI  - Vitamin D deficiency, oxidative stress and antioxidant status: only weak
      association seen in the absence of advanced age, obesity or pre-existing disease.
AB  - Vitamin D deficiency (plasma 25-hydroxycholecalciferol (25(OH)D)70 % of
      participants were vitamin D deficient. No significant correlations and no
      biomarker differences across 25(OH)D quartiles or groups were seen except for
      total antioxidant status. A weak direct association (r 0.252, P<0.05) was
      observed between 25(OH)D and FRAP, and those in the lowest 25(OH)D quartile and
      group had significantly lower FRAP values. Results did not reveal a clear link
      between vitamin D status and oxidative stress biomarkers in the absence of
      advanced age, obesity and disease, though some evidence of depleted antioxidant
      status in those with vitamin D deficiency was seen. Poor antioxidant status may
      pre-date increased oxidative stress. Study of effects of correction of deficiency
      on antioxidant status and oxidative stress in vitamin D-deficient but otherwise
      healthy subjects is needed.

PMID- 28758604
TI  - A new species of Procyrnea (Nematoda: Habronematidae) parasitic in Rhea pennata
      (Aves: Rheidae) from Patagonia, Argentina, with a key to species of the genus.
AB  - Procyrnea choique n. sp. is described from the lesser rhea, Rhea pennata
      d'Orbigny (Aves: Rheidae), from the Protected Natural Area Peninsula Valdes,
      Chubut province, Argentina. The new species resembles P. ficheuri, P. murrayi, P.
      excisiformis, P. dollfusi, P. haliasturi, P. anterovulvata, P. graculae, P.
      brevicaudata, P. uncinipenis, P. javaensis, P. ameerae, P. ornata, P. aegotheles,
      P. spiralis, P. ruschii and P. aptera, mainly in the absence of lateral alae; but
      differs from its congeners by having a left spicule without barbs, the position
      of the vulva which is post-equatorial, the absence of lateral ridges, absent
      median precloacal papilla, asymmetrical caudal alae, males more than 6 mm long,
      left spicule 1 mm long and spicule ratio 1:3. Our results extend the taxonomy of
      Procyrnea Chabaud, 1958 and comprise the first report of a habronematid from R.
      pennata. A key to species of Procyrnea is presented.

PMID- 28758605
TI  - Rescue extracorporeal membrane oxygenation therapy in methamphetamine toxicity.
AB  - Complications related to methamphetamine use and abuse are common presentations
      seen in the emergency department. Standard management focuses on addressing the
      central nervous system and cardiovascular effects with the use of sedation and
      hemodynamic support. We describe a case report of a patient with methamphetamine
      toxicity and subsequent severe cardiomyopathy refractory to conventional
      management that responded to cardiovascular support with extracorporeal membrane
      oxygenation therapy (ECMO). A 22-year-old female was admitted in severe
      cardiogenic shock following intravenous administration of methamphetamine and
      oral fentanyl use. Despite aggressive treatment with benzodiazepines, intravenous
      fluids, vasopressors, vasodilators, antibiotics and inotropes, the patient's
      clinical status deteriorated, and she suffered a cardiac arrest. The patient was
      successfully resuscitated, and following the return of spontaneous circulation,
      ECMO was initiated. After 82 hours the patient was successfully weaned from ECMO
      with the recovery of her left ventricular function and no neurologic sequelae.
      The patient developed leg ischemia requiring embolectomy and open repair as a
      complication of ECMO cannulation. In our case, ECMO was used successfully in
      treating severe cardiac dysfunction from acute methamphetamine-induced
      cardiomyopathy and was used as a bridge to recovery. The complications seen in
      this patient emphasize the potential risks associated with this intervention and
      highlight the need for careful patient selection.

PMID- 28758606
TI  - Emergency Preparedness in Elderly Care in Sweden: A Study of Staff Perspectives.
AB  - OBJECTIVE: The aim was to investigate the interface between elderly care and
      emergency preparedness from the elderly care staff's perspective. METHODS: A web
      based questionnaire was sent to elderly care staff in 4 Swedish municipalities.
      The questions involved experiences of extraordinary events, education and
      exercises, and risk and vulnerability analyses, evaluations of main risks and
      emergency preparedness, and familiarity with preparedness plans. In total, 568
      elderly care staff responded. RESULTS: Between 15% and 25% of the respondents
      claimed experiences of extraordinary events, exercises and education, and risk
      and vulnerability analyses. The same number claimed familiarity with the
      organization's preparedness plan, whereas ~85% answered that they need more
      education and exercises. Emergency preparedness was evaluated as important. The
      experiences and risks referred to pertained to both official categories used
      within emergency preparedness and issues such as work conditions, seniors' fall
      accidents. CONCLUSION: Elderly care staff, though highly motivated, do not seem
      to be involved in emergency preparedness and are not targeted to a large extent
      when education and training are organized. A development of the interface between
      emergency preparedness and elderly care could require a clarification of the
      scope and context of emergency preparedness and of differing understandings of
      central concepts. (Disaster Med Public Health Preparedness. 2018;12:86-93).

PMID- 28758607
TI  - Larval species composition and genetic structures of Carposina sasakii,
      Grapholita dimorpha, and Grapholita molesta from Korea.
AB  - Rapid determination of the larval species composition and understanding of their
      genetic structure is important to establish the appropriate management system for
      multiple species infesting in fruits. We established accurate and rapid
      diagnostic methods based on multiplex polymerase chain reaction (PCR) diagnostic
      techniques to discriminate the three major lepidopteran species in orchard,
      Carposina sasakii, Grapholita dimorpha, and Grapholita molesta. Each species was
      identified by amplifying species-specific PCR products (375 bp for C. sasakii,
      125 and 234 bp for G. dimorpha, and 125 bp for G. molesta). Based on species
      composition analysis from six types of infested fruits, G. dimorpha constituted
      the highest proportion (47.8%), followed by 35.2 and 13.5% for G. molesta and C.
      sasakii, respectively. Interestingly, high prevalence was found in G. dimorpha
      and G. molesta for plum and peach, respectively. Based on genetic diversity
      analysis, the three insect species exhibited moderate or high haplotype diversity
      and low nucleotide diversity, ranging from 0.319 to 0.699 and 0.0006 to 0.0045,
      respectively. Demographic expansion was not detected according to either a
      neutrality test or mismatch distribution analysis. Moreover, no significant
      genetic structure corresponding to province, host plant, fruit type, or
      collection period was observed. These results suggest that the population of each
      species would have high dispersal ability following fruit-generating periods via
      intrinsic host adaptation ability regardless of the spatial and temporal
      conditions. Determination of larval composition on fruit is valuable for
      establishing appropriate management systems that take the species into
      consideration; additionally, population genetic approaches can be utilized to
      understand the effects of environmental factors (province, host fruit, fruit
      type, etc.) on population structures.

PMID- 28758608
TI  - Pseudomonas aeruginosa Outbreak in a Neonatal Intensive Care Unit Attributed to
      Hospital Tap Water: Methodological and Statistical Issues to Avoid
      Misinterpretation.

PMID- 28758609
TI  - Lateral neck dissection affects the voice in thyroid cancer patients.
AB  - OBJECTIVE: This study aimed to identify the effect of lateral neck dissection on
      voice change in thyroidectomised patients. METHODS: Medical records from 264
      patients who underwent thyroidectomy with (n = 65) or without (n = 199) lateral
      neck dissection were reviewed. Clinical and voice evaluation data were compared
      between the two groups. RESULTS: Patients who underwent surgery that included
      lateral neck dissection had lower fundamental frequencies and speaking
      fundamental frequencies. They also had a higher incidence of asymmetric mucosal
      wave and vocal fold oedema on videostroboscopy during the first month after
      surgery, with the incidence of vocal fold oedema remaining significantly higher
      at three months. Self-assessed voice quality scores were significantly higher in
      lateral neck dissection patients at both one and three months after surgery.
      CONCLUSION: In thyroidectomised patients, lateral neck dissection lowers the
      vocal pitch in the initial period after surgery and induces vocal fold oedema
      that persists for several months. Although most objective parameters improved
      within a month, subjective symptoms lasted for longer.

PMID- 28758610
TI  - Reducing Second Gram-Negative Antibiotic Therapy on Pediatric Oncology and
      Hematopoietic Stem Cell Transplantation Services.
AB  - OBJECTIVE To evaluate interventions to reduce avoidable antibiotic use on
      pediatric oncology and hematopoietic stem cell transplantation (HSCT) services.
      DESIGN Interrupted time series. SETTING Academic pediatric hospital with separate
      oncology and HSCT services. PARTICIPANTS Children admitted to the services during
      baseline (October 2011-August 2013) and 2 intervention periods, September 2013
      June 2015 and July 2015-June 2016, including 1,525 oncology hospitalizations and
      301 HSCT hospitalizations. INTERVENTION In phase 1, we completed an update of the
      institutional febrile neutropenia (FN) guideline for the pediatric oncology
      service, recommending first-line beta-lactam monotherapy rather than routine use
      of 2 gram-negative agents. Phase 2 included updating the HSCT service FN
      guideline and engagement with a new pediatric antimicrobial stewardship program.
      The use of target antibiotics (tobramycin and ciprofloxacin) was measured in days
      of therapy per 1,000 patient days collected from administrative data.
      Intervention effects were evaluated using interrupted time series with segmented
      regression. RESULTS Phase 1 had mixed effects-long-term reduction in tobramycin
      use (97% below projected at 18 months) but rebound with increasing slope in
      ciprofloxacin use (+18% per month). Following phase 2, tobramycin and
      ciprofloxacin use on the oncology service were both 99% below projected levels at
      12 months. On the HSCT service, tobramycin use was 99% below the projected level
      and ciprofloxacin use was 96% below the projected level at 12 months. CONCLUSIONS
      Locally adapted guidelines can facilitate practice changes in oncology and HSCT
      settings. More comprehensive and ongoing interventions, including follow-up
      education, feedback, and engagement of companion services may be needed to
      sustain changes. Infect Control Hosp Epidemiol 2017;38:1039-1047.

PMID- 28758611
TI  - Parent-child conversations about literacy: a longitudinal, observational study.
AB  - Conversations about literacy-related matters with parents can help prepare
      children for formal literacy instruction. We studied these conversations using
      data gathered from fifty-six US families as they engaged in daily activities at
      home. Analyzing conversations when children were aged 1;10, 2;6, 3;6, and 4;2, we
      found that explicit talk about the elements and processes of reading and writing
      occurred even when children were less than two years old and became more common
      as children grew older. The majority of literacy-related conversations included
      talk about alphabet letters. Literacy-related conversations occurred in a variety
      of contexts, not only book-reading. There were few differences as a function of
      family socioeconomic status in the proportion of utterances during the sessions
      that occurred in literacy-related conversations. At older ages, however, children
      in families of lower socioeconomic status bore more of the conversational burden
      than children in families of higher status.

PMID- 28758612
TI  - Incidence of Extended-Spectrum beta-Lactamase (ESBL)-Producing Escherichia coli
      and Klebsiella Infections in the United States: A Systematic Literature Review.
AB  - BACKGROUND Despite a reported worldwide increase, the incidence of extended
      spectrum beta-lactamase (ESBL) Escherichia coli and Klebsiella infections in the
      United States is unknown. Understanding the incidence and trends of ESBL
      infections will aid in directing research and prevention efforts. OBJECTIVE To
      perform a literature review to identify the incidence of ESBL-producing E. coli
      and Klebsiella infections in the United States. DESIGN Systematic literature
      review. METHODS MEDLINE via Ovid, CINAHL, Cochrane library, NHS Economic
      Evaluation Database, Web of Science, and Scopus were searched for multicenter
      (>=2 sites), US studies published between 2000 and 2015 that evaluated the
      incidence of ESBL-E. coli or ESBL-Klebsiella infections. We excluded studies that
      examined resistance rates alone or did not have a denominator that included
      uninfected patients such as patient days, device days, number of admissions, or
      number of discharges. Additionally, articles that were not written in English,
      contained duplicated data, or pertained to ESBL organisms from food, animals, or
      the environment were excluded. RESULTS Among 51,419 studies examined, 9 were
      included for review. Incidence rates differed by patient population, time, and
      ESBL definition and ranged from 0 infections per 100,000 patient days to 16.64
      infections per 10,000 discharges and incidence rates increased over time from
      1997 to 2011. Rates were slightly higher for ESBL-Klebsiella infections than for
      ESBL-E. coli infections. CONCLUSION The incidence of ESBL-E. coli and ESBL
      Klebsiella infections in the United States has increased, with slightly higher
      rates of ESBL-Klebsiella infections. Appropriate estimates of ESBL infections
      when coupled with other mechanisms of resistance will allow for the appropriate
      targeting of resources toward research, drug discovery, antimicrobial
      stewardship, and infection prevention. Infect Control Hosp Epidemiol 2017;38:1209
      1215.

PMID- 28758614
TI  - The Ongoing Syrian Arab Republic Health Care Crisis.
AB  - Prior to the Syrian civil war, access and delivery of health care and health care
      information over the past 4 decades had steadily improved. The life expectancy of
      the average Syrian in 2012 was 75.7 years, compared to 56 years in 1970. As a
      result of the civil war, this trend has reversed, with the life expectancy
      reduced by 20 years from the 2012 level. The Syrian government and its allies
      have specifically targeted the health care infrastructure not under government
      control. (Disaster Med Public Health Preparedness. 2018;12:23-25).

PMID- 28758613
TI  - Developing measures of food and nutrition security within an Australian context.
AB  - OBJECTIVE: To develop a measure of food and nutrition security for use among an
      Australian population that measures all pillars of food security and to establish
      its content validity. DESIGN: The study consisted of two phases. Phase 1 involved
      focus groups with experts working in the area of food security. Data were
      assessed using content analysis and results informed the development of a draft
      tool. Phase 2 consisted of a series of three online surveys using the Delphi
      technique. Findings from each survey were used to establish content validity and
      progressively modify the tool until consensus was reached for all items. SETTING:
      Australia. SUBJECTS: Phase 1 focus groups involved twenty-five experts working in
      the field of food security, who were attending the Dietitians Association of
      Australia National Conference, 2013. Phase 2 included twenty-five experts working
      in food security, who were recruited via email. RESULTS: Findings from Phase 1
      supported the need for an Australian-specific tool and highlighted the failure of
      current tools to measure across all pillars of food security. Participants
      encouraged the inclusion of items to measure barriers to food acquisition and the
      previous single item to enable comparisons with previous data. Phase 2 findings
      informed the selection and modification of items for inclusion in the final tool.
      CONCLUSIONS: The results led to the development of a draft tool to measure food
      and nutrition security, and supported its content validity. Further research is
      needed to validate the tool among the Australian population and to establish
      inter- and intra-rater reliability.

PMID- 28758615
TI  - Determinants of Implementation of Isolation Precautions Against Infections by
      Multidrug-Resistant Microorganisms: A Hospital-Based, Multicenter, Observational
      Study.
AB  - OBJECTIVES We aimed to ascertain the factors associated with lack of isolation
      precautions (IP) in patients infected or colonized by third-generation
      cephalosporin-resistant Enterobacteriaceae (3GCR-E) and methicillin-resistant
      Staphylococcus aureus (MRSA) in hospital settings. DESIGN Prospective
      surveillance and audit of practices. SETTING The study included 4 university
      hospitals in Lyon, France. PARTICIPANTS All patients hospitalized between April
      and June in 2013 and 2015 were included. Case patients had >=1 clinical sample
      positive for MRSA and/or 3GCR-E. METHODS Factors associated with the lack of IP
      implementation were identified using multivariate logistic regression. The
      incidence of MDRO infections was expressed per 10,000 patient days. RESULTS
      Overall, 57,222 patients accounting for 192,234 patient days of hospitalization
      were included, and 635 (1.1%) MDRO cases were identified. MRSA incidence was 2.5
      per 10,000 patient days (95% confidence interval [95% CI], 2.1-3.0) and 3GCR-E
      incidence was 10.1 per 10,000 patient days (95% CI, 9.2-11.0), with no crude
      difference between 2013 and 2015 (P=.15 and P=.11, respectively). Among 3GCR-E,
      the main species were Escherichia coli (43.8%) and Klebsiella pneumoniae (31.0%).
      Isolation precautions were implemented in 78.5% of cases. Lack of IP
      implementation was independently associated with patient age, year, specialty,
      hospital, colonization compared with infection, and lack of medical prescription
      for IPs (adjusted odds ratio, 17.4; 95% CI, 8.5-35.8; P<.001). CONCLUSIONS MRSA
      and 3GCR-E infections and/or colonizations are frequent in healthcare settings,
      and IPs are implemented in most cases. When IPs are lacking, the main factor is
      the absence of medical prescription for IPs, underscoring the need for alerts to
      physicians by the microbiological laboratory and/or the infection control team.
      Infect Control Hosp Epidemiol 2017;38:1188-1195.

PMID- 28758616
TI  - Variable Case Detection and Many Unreported Cases of Surgical-Site Infection
      Following Colon Surgery and Abdominal Hysterectomy in a Statewide Validation.
AB  - OBJECTIVE To assess hospital surgical-site infection (SSI) identification and
      reporting following colon surgery and abdominal hysterectomy via a statewide
      external validation METHODS Infection preventionists (IPs) from the California
      Department of Public Health (CDPH) performed on-site SSI validation for surgical
      procedures performed in hospitals that voluntarily participated. Validation
      involved chart review of SSI cases previously reported by hospitals plus review
      of patient records flagged for review by claims codes suggestive of SSI. We
      assessed the sensitivity of traditional surveillance and the added benefit of
      claims-based surveillance. We also evaluated the positive predictive value of
      claims-based surveillance (ie, workload efficiency). RESULTS Upon validation
      review, CDPH IPs identified 239 SSIs following colon surgery at 42 hospitals and
      76 SSIs following abdominal hysterectomy at 34 hospitals. For colon surgery,
      traditional surveillance had a sensitivity of 50% (47% for deep incisional or
      organ/space [DI/OS] SSI), compared to 84% (88% for DI/OS SSI) for claims-based
      surveillance. For abdominal hysterectomy, traditional surveillance had a
      sensitivity of 68% (67% for DI/OS SSI) compared to 74% (78% for DI/OS SSI) for
      claims-based surveillance. Claims-based surveillance was also efficient, with 1
      SSI identified for every 2 patients flagged for review who had undergone
      abdominal hysterectomy and for every 2.6 patients flagged for review who had
      undergone colon surgery. Overall, CDPH identified previously unreported SSIs in
      74% of validation hospitals performing colon surgery and 35% of validation
      hospitals performing abdominal hysterectomy. CONCLUSIONS Claims-based
      surveillance is a standardized approach that hospitals can use to augment
      traditional surveillance methods and health departments can use for external
      validation. Infect Control Hosp Epidemiol 2017;38:1091-1097.

PMID- 28758617
TI  - Prevalence of pulmonary embolism in syncope patients.
AB  - : Clinical questionHow often is pulmonary embolism (PE) found in patients
      admitted for syncope?Article chosenPrandoni P, Lensing A, Prins M, et al.
      Prevalence of pulmonary embolism among patients hospitalized for syncope (PESIT).
      N Engl J Med 2016;375:1524-31, doi: 10.1056/NEJMoa1602172. OBJECTIVE: To
      determine the prevalence of PE in patients hospitalized for a first episode of
      syncope.

PMID- 28758618
TI  - Clinical Care of Hematological Patients in a Bone Marrow Transplant Unit: Do
      Human Resources Influence Infection Incidence?

PMID- 28758619
TI  - Sus scrofa papillomavirus 2 - genetic characterization of a novel suid
      papillomavirus from wild boar in Germany.
AB  - We identified a novel papillomavirus, Sus scrofa papillomavirus 2 (SsPV2), which
      is the first papillomavirus associated with papillomas in pigs. In skin
      alterations of a German wild boar, showing typical gross and histological
      appearance of papillomas, papillomavirus-like particles were demonstrated by
      electron microscopy. Degenerate papillomavirus-specific primers were used to
      amplify and sequence parts of the viral DNA. Subsequently, the complete genomic
      DNA was cloned and sequenced. The SsPV2 genome had a length of 8218 bp, encoded
      the early proteins E6, E7, E1 and E2, the late proteins L1 and L2 and contained
      an upstream regulatory region. Genomic characterization demonstrated
      papillomavirus-typical characteristics as well as unique features. For example,
      the E2 protein was significantly larger than in every other known papillomavirus
      species. Phylogenetic analysis was not able to relate SsPV2 unambiguously with
      other papillomavirus species or existing genera. Therefore, it might be
      representative of a new papillomavirus genus.

PMID- 28758620
TI  - Antibodies against the mono-methylated arginine-glycine repeat (MMA-RG) of the
      Epstein-Barr virus nuclear antigen 2 (EBNA2) identify potential cellular proteins
      targeted in viral transformation.
AB  - The Epstein-Barr virus is a human herpes virus with oncogenic potential. The
      virus-encoded nuclear antigen 2 (EBNA2) is a key mediator of viral tumorigenesis.
      EBNA2 features an arginine-glycine (RG) repeat at amino acids (aa)339-354 that is
      essential for the transformation of lymphocytes and contains symmetrically (SDMA)
      and asymmetrically (ADMA) di-methylated arginine residues. The SDMA-modified
      EBNA2 binds the survival motor neuron protein (SMN), thus mimicking SMD3, a
      cellular SDMA-containing protein that interacts with SMN. Accordingly, a
      monoclonal antibody (mAb) specific for the SDMA-modified RG repeat of EBNA2 also
      binds to SMD3. With the novel mAb 19D4 we now show that EBNA2 contains mono
      methylated arginine (MMA) residues within the RG repeat. Using 19D4, we immune
      precipitated and analysed by mass spectrometry cellular proteins in EBV
      transformed B-cells that feature MMA motifs that are similar to the one in EBNA2.
      Among the cellular proteins identified, we confirmed by immunoprecipitation
      and/or Western blot analyses Aly/REF, Coilin, DDX5, FXR1, HNRNPK, LSM4, MRE11,
      NRIP, nucleolin, PRPF8, RBM26, SMD1 (SNRDP1) and THRAP3 proteins that are either
      known to contain MMA residues or feature RG repeat sequences that probably serve
      as methylation substrates. The identified proteins are involved in splicing,
      tumorigenesis, transcriptional activation, DNA stability and RNA processing or
      export. Furthermore, we found that several proteins involved in energy metabolism
      are associated with MMA-modified proteins. Interestingly, the viral EBNA1 protein
      that features methylated RG repeat motifs also reacted with the antibodies. Our
      results indicate that the region between aa 34-52 of EBNA1 contains ADMA or SDMA
      residues, while the region between aa 328-377 mainly contains MMA residues.

PMID- 28758621
TI  - Paracoccus aerius sp. nov., isolated from air.
AB  - Strain 011410T, isolated from air at the foot of Xiangshan Mountain, Beijing,
      China, was Gram-reaction-negative, facultatively anaerobic, oval-shaped, motile
      with two flagella and catalase- and oxidase-positive. Growth of strain 011410T
      was observed at 4-41  degrees C (optimum, 30  degrees C), at pH 4.5-10.0
      (optimum, pH 8.0) and at salinities of 0-10 % (w/v) NaCl (optimum, 0-2 %).
      Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 011410T
      was a member of the genus Paracoccus and was related most closely to Paracoccus
      aestuarii B7T (96.62 % similarity) and Paracoccus sediminis CMB17T (96.48 %
      similarity). The major fatty acid was identified as C18 : 1omega7c, with smaller
      amounts of C18 : 0, C10 : 0 3-OH and summed feature 2 (C14 : 0 3-OH and/or iso
      C16 : 1 I). The predominant respiratory quinone was ubiquinone-10 (Q-10), with Q
      9 as a minor component. Polar lipid analysis indicated the presence of
      diphosphatidylglycerol, phosphatidylglycerol, one unknown phosphoglycolipid, five
      unknown phospholipids, one unknown aminolipid, one unknown glycolipid and two
      unknown polar lipids. The DNA G+C content of the strain was 63.5 mol%. On the
      basis of the data from this polyphasic characterization, strain 011410T
      represents a novel species, for which the name Paracoccus aerius sp. nov. is
      proposed. The type strain is 011410T (=CFCC 14285T=KCTC 42845T).

PMID- 28758622
TI  - Assemblins as maturational proteases in herpesviruses.
AB  - During assembly of herpesvirus capsids, a protein scaffold self-assembles to ring
      like structures forming the scaffold of the spherical procapsids. Proteolytic
      activity of the herpesvirus maturational protease causes structural changes that
      result in angularization of the capsids. In those mature icosahedral capsids, the
      packaging of viral DNA into the capsids can take place. The strictly regulated
      protease is called assemblin. It is inactive in its monomeric state and activated
      by dimerization. The structures of the dimeric forms of several assemblins from
      all herpesvirus subfamilies have been elucidated in the last two decades. They
      revealed a unique serine-protease fold with a catalytic triad consisting of a
      serine and two histidines. Inhibitors that disturb dimerization by binding to the
      dimerization area were found recently. Additionally, the structure of the
      monomeric form of assemblin from pseudorabies virus and some monomer-like
      structures of Kaposi's sarcoma-associated herpesvirus assemblin were solved.
      These findings are the proof-of-principle for the development of new anti
      herpesvirus drugs. Therefore, the most important information on this fascinating
      and unique class of proteases is summarized here.

PMID- 28758623
TI  - Risk factors and predictors of carbapenem-resistant Pseudomonas aeruginosa and
      Acinetobacter baumannii mortality in critically ill bacteraemic patients over a 6
      year period (2010-15): antibiotics do matter.
AB  - PURPOSE: Acinetobacter baumannii and Pseudomonas aeruginosa provoke serious
      infections, especially in intensive care unit (ICU) patients. METHODOLOGY: The
      risk factors and predictors of mortality for P. aeruginosa (n=84; 46 carbapenem
      resistant) and A. baumannii (n=129; all carbapenem-resistant) bloodstream
      infections (BSIs) in an ICU were evaluated. Antibiotic susceptibility testing was
      performed using the agar disk diffusion method according to EUCAST guidelines.
      The minimum inhibitory concentration was determined by a gradient method (Etest).
      Multilocus sequence typing (MLST) was performed for P. aeruginosa during the
      carbapenem-resistant outbreak in 2014. Epidemiological data were collected from
      the patients' chart reviews.Results/Key findings. Hospitalization during the
      summer months, prior KPC-producing Klebsiella pneumoniae (KPC-Kp) BSI, and the
      administration of tigecycline, aminoglycosides and cortisone were independently
      associated with P. aeruginosa BSIs. MLST revealed the dissemination of clone
      ST227, including carbapenem-resistant P. aeruginosa strains. Hospitalization
      during the summer months, prior KPC-Kp BSI, and the administration of
      antibiotics, carbapenem and cortisone were independently associated with A.
      baumannii BSIs. The 30-day mortality rate for P. aeruginosa and A. baumannii BSI
      was 45.2 and 39.5 %, respectively. Sequential organ failure assessment (SOFA)
      score at onset, septic shock, age, and prior KPC-Kp BSI were significantly
      associated with P. aeruginosa BSI mortality. The administration of at least one
      active antibiotic was identified as a predictor of a good prognosis. Septic shock
      and simplified acute physiology score (SAPS) II at onset were independently
      associated with A. baumannii BSI mortality. The administration of at least one
      active antibiotic and colistin-vancomycin co-administration were identified as
      predictors of a good prognosis. CONCLUSION: KPC-Kp infection predisposes ICU
      patients to BSI by either A. baumannii or P. aeruginosa. The administration of at
      least one active antibiotic leads to better survival rates.

PMID- 28758624
TI  - TolC2 is required for the resistance, colonization and virulence of
      Actinobacillus pleuropneumoniae.
AB  - PURPOSE: To colonize and cause infection in the host, pathogens must be well
      equipped to respond to and survive in several hostile conditions. TolC, an outer
      membrane channel component used by multidrug efflux pumps and type I secretion
      systems, is considered to be largely involved in bacterial physiology and
      virulence. In this study, we attempted to investigate the possible roles of
      TolC2, a homologue of TolC, in the pathogenesis of Actinobacillus
      pleuropneumoniae. METHODOLOGY: The cell viability was investigated under stress
      conditions (oxidative, thermal, acid and osmotic). Virulence was assessed by
      lethal intraperitoneal injection of mice. The underlying mechanisms of the
      attenuation were further explored by serum bactericidal, in vivo phagocytosis and
      organ burden assays.Results/Key findings. The deletion of tolC2 caused increased
      sensitivity to oxidative, thermal and acid challenges, indicating a critical role
      of TolC2 in A. pleuropneumoniae survival under stress conditions. The
      intraperitoneal injection of mice showed that the DeltatolC2 mutant caused
      significantly decreased mortality, suggesting the involvement of TolC2 in the
      virulence of A. pleuropneumoniae. In the serum-killing assays, the DeltatolC2
      mutant showed significantly reduced survival ability when exposed to fresh serum.
      By the in vivo phagocytosis assays, we found that the loss of tolC2 rendered the
      mutant susceptible to phagocytosis by macrophages. Finally, the organ burden
      assays revealed decreased colonization of DeltatolC2 in lungs, indicating a
      higher bacterial clearance rate in mice in the absence of TolC2. CONCLUSION: Our
      findings demonstrate that TolC2 contributes to the virulence of A.
      pleuropneumoniae by helping survival and maximal colonization in the host.

PMID- 28758625
TI  - The dengue virus non-structural protein 1 (NS1) is secreted from infected
      mosquito cells via a non-classical caveolin-1-dependent pathway.
AB  - Dengue virus NS1 is a glycoprotein of 46-50 kDa that is conserved among
      flaviviruses, associates as a dimer to cell membranes and is secreted as a
      hexamer to the extracellular milieu. Recent evidence showed that NS1 is secreted
      efficiently from infected mosquito cells. To explore the secretory route of NS1
      in mosquito cells, infected cells were treated with brefeldin A (BFA) and methyl
      beta-cyclodextrin (MbetaCD). The results showed that MbetaCD, but not BFA,
      significantly reduced the release of NS1. Moreover, silencing the expression of
      caveolin-1 (CAV1; a key component of the caveolar system that transports
      cholesterol inside the cell), but not SAR1 (a GTPase that participates in the
      classical secretory pathway), also results in a significant reduction of the
      secretion of NS1. These results indicate that NS1 is released from mosquito cells
      via an unconventional secretory route that bypasses the Golgi complex, with the
      participation of CAV1. In agreement with this notion, differences were observed
      in the glycosylation status between secreted NS1 and E proteins. Classical
      mechanics and docking simulations suggested highly favoured interactions between
      the caveolin-binding domain present in NS1 and the scaffolding domain of CAV1.
      Finally, proximity ligation assays showed direct interaction between NS1 and CAV1
      in infected mosquito cells. These findings are in line with the lipoprotein
      nature of secreted NS1 and provide new insights into the biology of NS1.

PMID- 28758626
TI  - Aliifodinibius salicampi sp. nov., a moderately halophilic bacterium isolated
      from a grey saltern.
AB  - Three strains of a Gram-stain-negative, moderately halophilic bacterium,
      designated strain KHM44T, KHM29 and HHM4, were isolated from the sediment of a
      grey saltern located on Sinui island at Shinan, Korea. The isolates were aerobic,
      non-motile rods and grew at 15-50  degrees C (optimum, 37  degrees C), at pH 6.0
      9.0 (optimum, pH 8.0) and at salinities of 3-25 % (w/v) NaCl (optimum, 10 %
      NaCl). The predominant isoprenoid quinone was menaquinone-7 (MK-7), and the major
      fatty acids were iso-C15 : 0, C16 : 1omega7c and/or iso-C15 : 0 2-OH, iso-C17 :
      1omega9c and anteiso-C15 : 0. The polar lipids were diphosphatidylglycerol,
      phosphatidylcholine, phosphatidylethanolamine and glycolipid. The DNA G+C
      contents were 48.5-48.7 mol%. Phylogenetic analyses based on 16S rRNA gene
      sequences indicated that strains KHM44T, KHM29 and HHM4 belonged to the genus
      Aliifodinibius in the family Balneolaceae, with sequence similarities of 95.1
      97.2 % to members of this genus. Levels of DNA-DNA relatedness between strain
      KHM44T and the type strains of the other species of the genus Aliifodinibius
      ranged from 35.4 to 48.0 %. On the basis of polyphasic analysis from this study,
      strains KHM44T, KHM29 and HHM4 are considered to represent a novel species of the
      genus Aliifodinibius, for which the name Aliifodinibius salicampi sp. nov. is
      proposed. The type strain is KHM44T (=KACC 19060T=NBRC 112531T).

PMID- 28758627
TI  - Natronospira proteinivora gen. nov., sp. nov, an extremely salt-tolerant,
      alkaliphilic gammaproteobacterium from hypersaline soda lakes.
AB  - Brine samples from Kulunda Steppe soda lakes (Altai, Russia) were inoculated into
      a hypersaline alkaline mineral medium with beta-keratin (chicken feather) as a
      substrate. The micro-organisms dominating the enrichment culture were isolated by
      limiting serial dilution on the same medium with casein as a substrate. The cells
      of strain BSker1T were motile, curved rods. The strain was an obligately aerobic
      heterotroph utilizing proteins and peptides as growth substrates. The isolate was
      an obligate alkaliphile with a pH range for growth from pH 8.5 to 10.25 (optimum
      at pH 9.5), and it was extremely salt tolerant, growing with between 1 and 4.5 M
      total Na+ (optimally at 2-2.5 M). BSker1T had a unique composition of polar lipid
      fatty acids, dominated by two C17 species. The membrane polar lipids included
      multiple unidentified phospholipids and two aminolipids. According to
      phylogenetic analysis of the 16S rRNA gene sequence, the isolate forms a novel
      branch within the family Ectothiorhodospiraceae (class Gammaproteobacteria) with
      the highest sequence similarity to the members of this family being 91 %. On the
      basis of distinct phenotypic and genotypic properties, strain BSker1T (=JCM
      31341T=UNIQEM U1008T) is proposed to be classified as a representative of a novel
      genus and species, Natronospira proteinivora gen. nov., sp. nov.

PMID- 28758628
TI  - Dictyobacter aurantiacus gen. nov., sp. nov., a member of the family
      Ktedonobacteraceae, isolated from soil, and emended description of the genus
      Thermosporothrix.
AB  - A mesophilic, Gram-stain-positive, spore-forming bacterium that formed branched
      mycelia was isolated from paddy soil in Gunung Salak (Mount Salak), West Java,
      Indonesia. This strain, designated S-27T, grew at temperatures between 20 and 37 
      degrees C; the optimum growth temperature was 25 to 30  degrees C, and no growth
      was observed at 15 or 45  degrees C. The pH range for growth was pH 3.5 to 8.6;
      the optimum pH was 6.0, and no growth was observed at pH 3.0 or 9.2. Strain S-27T
      was able to hydrolyse polysaccharides such as starch, cellulose and xylan. The
      G+C content of the DNA of strain S-27T was 55.7 mol%. The major fatty acids were
      iso-C17 : 0 and C16 : 1 2-OH, and the major menaquinone was MK-9 (H2). The cell
      wall of strain S-27T contained d-glutamic acid, glycine, l-alanine, d-alanine, l
      ornithine and beta-alanine in a molar ratio of 1.0 : 1.6 : 1.4 : 0.6 : 0.9 : 1.1.
      The polar lipids consisted of phosphatidylglycerol, phosphatidylinositol and two
      glycolipids. The major cell-wall sugar was arabinose. Detailed phylogenetic
      analysis based on 16S rRNA gene sequences indicated that strain S-27T belongs to
      the order Ktedonobacterales and is most closely related to Ktedonobacter
      racemifer SOSP1-21T (89.6 % sequence identity). On the basis of its
      chemotaxonomic and phenotypic features and phylogenetic position, we concluded
      that strain S-27T represents a novel genus and species, for which we propose the
      name Dictyobacter aurantiacus gen. nov., sp. nov. The type strain of Dictyobacter
      aurantiacus is strain S-27T (=NBRC 109595T=InaCC B312T). Emendation of the
      description of the genus Thermosporothrix is also provided.

PMID- 28758629
TI  - Identification and characterization of a Golgi retention signal in feline
      coronavirus accessory protein 7b.
AB  - Feline coronaviruses encode five accessory proteins with largely elusive
      functions. Here, one of these proteins, called 7b (206 residues), was
      investigated using a reverse genetic approach established for feline infectious
      peritonitis virus (FIPV) strain 79-1146. Recombinant FIPVs (rFPIVs) expressing
      mutant and/or FLAG-tagged forms of 7b were generated and used to investigate the
      expression, processing, glycosylation, localization and trafficking of the 7b
      protein in rFIPV-infected cells, focusing on a previously predicted ER retention
      signal, KTEL, at the C-terminus of 7b. The study revealed that 7b is N-terminally
      processed by a cellular signalase. The cleavage site, 17-Ala|Thr-18, was
      unambiguously identified by N-terminal sequence analysis of a 7b processing
      product purified from rFIPV-infected cells. Based on this information, rFIPVs
      expressing FLAG-tagged 7b proteins were generated and the effects of
      substitutions in the C-terminal 202KTEL206 sequence were investigated. The data
      show that (i) 7b localizes to and is retained in the medial- and/or trans-Golgi
      compartment, (ii) the C-terminal KTEL sequence acts as a Golgi [rather than an
      endoplasmic reticulum (ER)] retention signal, (iii) minor changes in the KTEL
      motif (such as KTE, KTEV, or the addition of a C-terminal tag) abolish Golgi
      retention, resulting in relocalization and secretion of 7b, and (iv) a KTEL-to
      KDEL replacement causes retention of 7b in the ER of rFIPV-infected feline cells.
      Taken together, this study provides interesting new insights into an efficient
      Golgi retention signal that controls the cellular localization and trafficking of
      the FIPV 7b protein in virus-infected feline cells.

PMID- 28758630
TI  - 'Candidatus Phytoplasma luffae', a novel taxon associated with witches' broom
      disease of loofah, Luffa aegyptica Mill.
AB  - The phytoplasma associated with witches' broom disease of loofah [Luffa aegyptica
      Mill., syn. Luffa cylindrica (L.) M.J. Roem.] in Taiwan was classified in group
      16SrVIII, subgroup A (16SrVIII-A), based on results from actual and in silico
      RFLP analysis of 16S rRNA gene sequences. Nucleotide sequencing of PCR-amplified,
      cloned DNA segments revealed rrn interoperon sequence heterogeneity in the loofah
      witches' broom (LfWB) phytoplasma. Whereas the 16S-23S rRNA spacer region of rrnA
      contained a complete tRNA-Ile gene, the spacer of rrnB contained a nonfunctional
      remnant of a tRNA gene. Phylogenetic analysis of the rrnA and rrnB 16S rRNA genes
      revealed that the LfWB phytoplasma represented a distinct lineage within the
      phytoplasma clade, and the LfWB phytoplasma shared less than 97.5 % nucleotide
      sequence similarity of 16S rRNA genes with previously described
      'CandidatusPhytoplasma' taxa. Based on unique properties of DNA, we propose
      recognition of loofah witches' broom phytoplasma strain LfWBR as representative
      of a novel taxon, 'CandidatusPhytoplasma luffae'.

PMID- 28758631
TI  - Statins are ineffective at reducing neuroinflammation or prolonging survival in
      scrapie-infected mice.
AB  - Neuroinflammation is a prominent component of several neurodegenerative diseases,
      including multiple sclerosis, Alzheimer's disease, Parkinson's disease,
      tauopathies, amyotrophic lateral sclerosis and prion diseases. In such
      conditions, the ability to decrease neuroinflammation by drug therapy may
      influence disease progression. Statins have been used to treat hyperlipidemia as
      well as reduce neuroinflammation and oxidative stress in various tissues. In
      previous studies, treatment of scrapie-infected mice with the type 1 statins,
      simvastatin or pravastatin, showed a small beneficial effect on survival time. In
      the current study, to increase the effectiveness of statin therapy, we treated
      infected mice with atorvastatin, a type 2 statin that has improved
      pharmacokinetics over many type 1 statins. Treatments with either simvastatin or
      pravastatin were tested for comparison. We evaluated scrapie-infected mice for
      protease-resistant PrP (PrPres) accumulation, gliosis, neuroinflammation and time
      until advanced clinical disease requiring euthanasia. All three statin treatments
      reduced total serum cholesterol >=40 % in mice. However, gliosis and PrPres
      deposition were similar in statin-treated and untreated infected mice. Time to
      euthanasia due to advanced clinical signs was not changed in statin-treated mice
      relative to untreated mice, a finding at odds with previous reports. Expression
      of 84 inflammatory genes involved in neuroinflammation was also quantitated.
      Seven genes were reduced by pravastatin, and one gene was reduced by
      atorvastatin. In contrast, simvastatin therapy did not reduce any of the tested
      genes, but did slightly increase the expression of Ccl2 and Cxcl13. Our studies
      indicate that none of the three statins tested were effective in reducing scrapie
      induced neuroinflammation or neuropathogenesis.

PMID- 28758632
TI  - Tree shrew, a potential animal model for hepatitis C, supports the infection and
      replication of HCV in vitro and in vivo.
AB  - The tree shrew (Tupaia belangeri chinensis), a small animal widely distributed in
      Southeast Asia and southwest China, has the potential to be developed as an
      animal model for hepatitis C. To determine the susceptibility of the tree shrew
      to hepatitis C virus (HCV) infection in vitro and in vivo, a well-established
      HCV, produced from the J6/JFH1-Huh7.5.1 culture system, was used to infect
      cultured primary tupaia hepatocytes (PTHs) and tree shrews. The in vitro results
      showed that HCV genomic RNA and HCV-specific nonstructural protein 5A (NS5A)
      could be detected in the PTH cell culture from days 3-15 post-infection, although
      the viral load was lower than that observed in Huh7.5.1 cell culture. The
      occurrence of five sense mutations [S391A, G397A, L402F and M405T in the
      hypervariable region 1 (HVR1) of envelope glycoprotein 2 and I2750M in NS5B]
      suggested that HCV undergoes genetic evolution during culture. Fourteen of the 30
      experimental tree shrews (46.7 %) were found to be infected, although the HCV
      viremia was intermittent in vivo. A positive test for HCV RNA in liver tissue
      provided stronger evidence for HCV infection and replication in tree shrews. The
      results of an immunohistochemistry assay also demonstrated the presence of four
      HCV-specific proteins (Core, E2, NS3/4 and NS5A) in the hepatocytes of infected
      tree shrews. The pathological changes observed in the liver tissue of infected
      tree shrews could be considered to be representative symptoms of mild hepatitis.
      These results revealed that the tree shrew can be used as an animal model
      supporting the infection and replication of HCV in vitro and in vivo.

PMID- 28758633
TI  - Cyberlindnera tropicalis f.a., sp. nov., a novel yeast isolated from tropical
      regions.
AB  - Two yeast strains, DMKU-WBBC14 and UFMG-CM-Y3283, were isolated from soil in
      Samutprakarn province in the central part of Thailand and from rotting wood in an
      Amazonian forest site in the Roraima State in Brazil, respectively. The two
      strains showed identical sequences of the D1/D2 domain of the large subunit (LSU)
      rRNA gene and different sequences by three nucleotide substitutions of the
      internal transcribed spacer (ITS) region. Therefore, these two strains
      represented a single species which was most closely related to Cyberlindnera
      mengyuniae CBS 10845T. The nucleotide sequence differences between the two
      strains of the novel species and the type strain Cyberlindnera mengyuniae CBS
      10845T were 10 substitutions in the D1/D2 region of the LSU rRNA gene and 46
      substitutions in the ITS region. DMKU-WBBC14 and UFMG-CM-Y3283 differed in growth
      temperature profiles. Moreover, they also exhibited different carbon assimilation
      profiles and growth temperature profiles from the type strain of Cyberlindnera
      mengyuniae, CBS 10845T. The name Cyberlindnera tropicalis f.a., sp. nov. is
      proposed. The type strain is DMKU-WBBC14T (=CBS 14558T=TBRC 6562T). The Mycobank
      number is MB 819722.

PMID- 28758635
TI  - Cluster-distinguishing genotypic and phenotypic diversity of carbapenem-resistant
      Gram-negative bacteria in solid-organ transplantation patients: a comparative
      study.
AB  - PURPOSE: Solid-organ transplant recipients may display high rates of colonization
      and/or infection by multidrug-resistant bacteria. We analysed and compared the
      phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of
      Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii
      isolated from patients in the Solid Organ Transplantation department of our
      hospital. METHODOLOGY: Between March 2012 and August 2013, 56 CR strains from
      various biological fluids underwent antimicrobial susceptibility testing with
      VITEK 2, molecular analysis by PCR amplification and genotypic analysis with
      pulsed-field gel electrophoresis (PFGE). They were clustered according to
      antimicrobial drug susceptibility and genotypic profiles. Diversity analyses were
      performed by calculating Simpson's diversity index and applying computed
      rarefaction curves.Results/Key findings. Among K. pneumoniae, KP-producers
      predominated (57.1 %). VIM and OXA-23 carbapenemases prevailed among P.
      aeruginosa and A. baumannii (89.4 and 88.9 %, respectively). KPC-producing K.
      pneumoniae and OXA-23 A. baumannii were assigned in single PFGE pulsotypes. VIM
      producing P. aeruginosa generated multiple pulsotypes. CR K. pneumoniae strains
      displayed phenotypic diversity in tigecycline, colistin (CS), amikacin (AMK),
      gentamicin (GEN) and co-trimoxazole (SXT) (16 clusters); P. aeruginosa displayed
      phenotypic diversity in cefepime (FEP), ceftazidime, aztreonam, piperacillin,
      piperacillin-tazobactam, AMK, GEN and CS (9 clusters); and A. baumannii displayed
      phenotypic diversity in AMK, GEN, SXT, FEP, tobramycin and rifampicin (8
      clusters). The Simpson diversity indices for the interpretative phenotype and
      PFGE analysis were 0.89 and 0.6, respectively, for K. pneumoniae strains
      (P<0.001); 0.77 and 0.6 for P. aeruginosa (P=0.22); and 0.86 and 0.19 for A.
      baumannii (P=0.004). CONCLUSION: The presence of different antimicrobial
      susceptibility profiles does not preclude the possibility that two CR K.
      pneumoniae or A. baumannii isolates are clonally related.

PMID- 28758634
TI  - The genomic evolution of H1 influenza A viruses from swine detected in the United
      States between 2009 and 2016.
AB  - Transmission of influenza A virus (IAV) from humans to swine occurs with relative
      frequency and is a critical contributor to swine IAV diversity. Subsequent to the
      introduction of these human seasonal lineages, there is often reassortment with
      endemic viruses and antigenic drift. To address whether particular genome
      constellations contributed to viral persistence following the introduction of the
      2009 H1N1 human pandemic virus to swine in the USA, we collated and analysed 616
      whole genomes of swine H1 isolates. For each gene, sequences were aligned, the
      best-known maximum likelihood phylogeny was inferred, and each virus was assigned
      a clade based upon its evolutionary history. A time-scaled Bayesian approach was
      implemented for the haemagglutinin (HA) gene to determine the patterns of genetic
      diversity over time. From these analyses, we observed an increase in genome
      diversity across all H1 lineages and clades, with the H1-gamma and H1-delta1
      genetic clades containing the greatest number of unique genome patterns. We
      documented 74 genome patterns from 2009 to 2016, of which 3 genome patterns were
      consistently detected at a significantly higher level than others across the
      entire time period. Eight genome patterns increased significantly, while five
      genome patterns were shown to decline in detection over time. Viruses with genome
      patterns identified as persisting in the US swine population may possess a
      greater capacity to infect and transmit in swine. This study highlights the
      emerging genetic diversity of US swine IAV from 2009 to 2016, with implications
      for swine and public health and vaccine control efforts.

PMID- 28758636
TI  - The Pseudomonas aeruginosa dnaK gene is involved in bacterial translocation
      across the intestinal epithelial cell barrier.
AB  - Pseudomonas aeruginosa can penetrate through polarized epithelial cell monolayers
      produced by the human adenocarcinoma cell line Caco-2. We previously identified
      genes associated with bacterial translocation through Caco-2 cell monolayers by
      analysing transposon insertion mutants with dramatically reduced penetration
      activity relative to that of the wild-type P. aeruginosa PAO1 strain. In this
      study, we focused on the dnaK mutant because the association between this gene
      and penetration activity is unknown. Inactivation of dnaK caused significant
      repression of bacterial penetration through Caco-2 cell monolayers, with
      decreased swimming, swarming and twitching motilities; bacterial adherence; and
      fly mortality rate; as well as dramatic repression of type III effector secretion
      and production of elastase and exotoxin A. However, type IV pilus protein PilA
      expression was not affected. These results suggest that dnaK is associated with
      bacterial motility and adherence, which are mediated by flagella and pili, and
      with toxin secretion, which plays a key role in the penetration of P. aeruginosa
      through Caco-2 cell monolayers. Inactivation of P. aeruginosa dnaK function may
      interfere with bacterial translocation and prevent septicaemia caused by P.
      aeruginosa.

PMID- 28758639
TI  - Nano-friction behavior of phosphorene.
AB  - Nano-friction of phosphorene plays a significant role in affecting the
      controllability and efficiency of applying strain engineering to tune its
      properties. So far, the friction behavior of phosphorene has not been studied.
      This work studies the friction of single-layer and bilayer phosphorene on an
      amorphous silicon substrate by sliding a rigid tip. For the single-layer
      phosphorene, it is found that its friction is highly anisotropic, i.e. the
      friction is larger along the armchair direction than that along the zigzag
      direction. Moreover, pre-strain of the phosphorene also exhibits anisotropic
      effects. The friction increases with the pre-strain along the zigzag direction,
      but decreases with that along the armchair direction. Furthermore, the strong
      adhesion between the phosphorene and its substrate increases the friction between
      the phosphorene and the tip. For bilayer phosphorene, its friction highly depends
      on its stacking mode, which determines the contact interface with a commensurate
      or incommensurate pattern. This friction behavior is quite unique and greatly
      differs from that of graphene and molybdenum disulfide. Detailed analysis reveals
      that this behavior results from the combination effect of the friction contact
      area, the potential-energy profile of phosphorene, and its unique elongation.

PMID- 28758637
TI  - DNA prime/protein boost vaccination elicits robust humoral response in rhesus
      macaques using oligomeric simian immunodeficiency virus envelope and Advax delta
      inulin adjuvant.
AB  - The partial success of the RV144 trial underscores the importance of envelope
      specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1
      envelope proteins delivered with a potent adjuvant are expected to elicit strong
      antibody responses with broad neutralization specificity. To test this
      hypothesis, two SIV envelope proteins were formulated with delta inulin-based
      adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140-gp145
      from SIVmac251 and SIVsmE660 was purified to homogeneity. Oligomers showed high
      affinity interaction with CD4 and were highly immunogenic in rabbits, inducing
      Tier 2 SIV-neutralizing antibodies. The immunogenicity of an oligomeric Env DNA
      prime and protein boost together with Advax was evaluated in Chinese rhesus
      macaques. DNA administration elicited antibodies to both envelopes, and titres
      were markedly enhanced following homologous protein boosts via intranasal and
      intramuscular routes. Strong antibody responses were detected against the V1 and
      V2 domains of gp120. During peak immune responses, a low to moderate level of
      neutralizing activity was detected against Tier 1A/1B SIV isolates, with a
      moderate level noted against a Tier 2 isolate. Increased serum antibody affinity
      to SIVmac251 gp140 and generation of Env-specific memory B cells were observed in
      the immunized macaques. Animals were subjected to low-dose intravaginal challenge
      with SIVmac251 one week after the last protein boost. One out of three immunized
      animals was protected from infection. Although performed with a small number of
      macaques, this study demonstrates the utility of oligomeric envelopes formulated
      with Advax in eliciting broad antibody responses with the potential to provide
      protection against SIV transmission.

PMID- 28758640
TI  - Manifestation of hopping conductivity and granularity within phase diagrams of
      LaO1-x F x BiS2, Sr1-x La x FBiS2 and related BiS2-based compounds.
AB  - Layered BiS [Formula: see text] -based series, such as LaO [Formula: see text] F
      [Formula: see text] BiS [Formula: see text] and Sr [Formula: see text] La
      [Formula: see text] FBiS [Formula: see text] , offer ideal examples for studying
      normal and superconducting phase diagram of a solid solution that evolves from a
      nonmagnetic band-insulator parent. We constructed typical [Formula: see text]
      phase diagrams of these systems based on events occurring in thermal evolution of
      their electrical resistivity, [Formula: see text]. Overall evolution of these
      diagrams can be rationalized in terms of (i) Mott-Efros-Shklovskii scenario
      which, within the semiconducting [Formula: see text] regime ([Formula: see text]
      metal-insulator transition), describes the doping influence on the thermally
      activated hopping conductivity. (ii) A granular metal (superconductor) scenario
      which, within [Formula: see text], describes the evolution of normal and
      superconducting properties in terms of conductance g, Coulomb charging energy E c
      and Josephson coupling J; their joint influence is usually captured within a
      [Formula: see text] phase diagram. Based on analysis of the granular character of
      [Formula: see text], we converted the [Formula: see text] diagrams into projected
      g - T diagrams which, being fundamental, allow a better understanding of
      evolution of various granular-related properties (in particular the hallmarks of
      normal-state [Formula: see text] feature and superconductor-insulator transition)
      and how such properties are influenced by x, pressure or heat treatment.

PMID- 28758638
TI  - Influenza virus recruits host protein kinase C to control assembly and activity
      of its replication machinery.
AB  - Influenza virus expresses transcripts early in infection and transitions towards
      genome replication at later time points. This process requires de novo assembly
      of the viral replication machinery, large ribonucleoprotein complexes (RNPs)
      composed of the viral polymerase, genomic RNA and oligomeric nucleoprotein (NP).
      Despite the central role of RNPs during infection, the factors dictating where
      and when they assemble are poorly understood. Here we demonstrate that human
      protein kinase C (PKC) family members regulate RNP assembly. Activated PKCdelta
      interacts with the polymerase subunit PB2 and phospho-regulates NP
      oligomerization and RNP assembly during infection. Consistent with its role in
      regulating RNP assembly, knockout of PKCdelta impairs virus infection by
      selectively disrupting genome replication. However, primary transcription from
      pre-formed RNPs deposited by infecting particles is unaffected. Thus, influenza
      virus exploits host PKCs to regulate RNP assembly, a step required for the
      transition from primary transcription to genome replication during the infectious
      cycle.

PMID- 28758641
TI  - DropConnected neural networks trained on time-frequency and inter-beat features
      for classifying heart sounds.
AB  - OBJECTIVE: Automatic heart sound analysis has the potential to improve the
      diagnosis of valvular heart diseases in the primary care phase, as well as in
      countries where there is neither the expertise nor the equipment to perform
      echocardiograms. An algorithm has been trained, on the PhysioNet open-access
      heart sounds database, to classify heart sounds as normal or abnormal. APPROACH:
      The heart sounds are segmented using an open-source algorithm based on a hidden
      semi-Markov model. Following this, the time-frequency behaviour of a single
      heartbeat is characterized by using a novel implementation of the continuous
      wavelet transform, mel-frequency cepstral coefficients, and certain complexity
      measures. These features help detect the presence of any murmurs. A number of
      other features are also extracted to characterise the inter-beat behaviour of the
      heart sounds, which helps to recognize diseases such as arrhythmia. The extracted
      features are normalized and their dimensionality is reduced using principal
      component analysis. They are then used as the input to a fully-connected, two
      hidden-layer neural network, trained by error backpropagation, and regularized
      with DropConnect. MAIN RESULTS: This algorithm achieved an accuracy of 85.2% on
      the test data, which placed third in the PhysioNet/Computing in Cardiology
      Challenge (first place scored 86.0%). However, this is unrealistic of real-world
      performance, as the test data contained a dataset (dataset-e) in which normal and
      abnormal heart sounds were recorded with different stethoscopes. A 10-fold cross
      validation study on the training data (excluding dataset-e) gives a mean score of
      74.8%, which is a more realistic estimate of accuracy. With dataset-e excluded
      from training, the algorithm scored only 58.1% on the test data.

PMID- 28758642
TI  - Corrigendum: Role of phosphatase activity of soluble epoxide hydrolase in
      regulating simvastatin-activated endothelial nitric oxide synthase.
AB  - This corrects the article DOI: 10.1038/srep13524.

PMID- 28758643
TI  - Complement Gene Expression Correlates with Superior Frontal Cortical Thickness in
      Humans.
AB  - Recent work suggests that genes encoding complement proteins that are active in
      the innate immune system may confer risk for schizophrenia by disrupting typical
      synaptic pruning in late adolescence. Alterations in the complement pathway may
      contribute to aberrant cortical thinning in schizophrenia prodromes and reduced
      prefrontal cortical thickness in chronic schizophrenia patients; however, this
      theory needs to be translated to humans. We conducted a series of analyses in a
      sample of adult Swedish twins enriched for schizophrenia (N=129) to assess the
      plausibility of a relationship between complement gene expression and cortical
      thickness that could go awry in the etiology of schizophrenia. First, we
      identified that peripheral mRNA expression levels of two complement genes (C5,
      SERPING1) made unique contributions to the variance in superior frontal cortical
      thickness among all participants. Vertex-wise maps of the association between
      gene expression levels and thickness across the cortex suggested that this
      relationship was especially strong with SERPING1 in the superior frontal region,
      consistent with the pattern of disruption in cortical thickness observed in
      schizophrenia. Additional analyses identified that these genes are expressed in
      the human superior frontal cortex, that heritable genetic factors influence
      SERPING1 gene expression levels, and that these associations are observed
      regardless of case status. These findings provide initial evidence linking the
      complement system with cortical thinning in humans, a process potentially
      involved in the pathogenesis of schizophrenia.

PMID- 28758645
TI  - Fluorometric gas-imaging system (sniff-cam), using the extinction of NADH with an
      ADH reverse reaction, for acetaldehyde in the gas phase.
AB  - A gas-imaging system (sniff-cam) that allows fluorometric visualization of a two
      dimensional (2-D) distribution of gaseous acetaldehyde (AcH) was developed. It
      employed a reverse reaction of a nicotinamide adenine dinucleotide (NADH)
      dependent enzyme that led to consumption of NADH in that reaction. The system was
      constructed with a highly sensitive camera, an ultraviolet light emitting diode
      array sheet, two band pass filters and an alcohol dehydrogenase (ADH)-immobilized
      mesh that was used for AcH detection. The reverse reaction of the ADH catalyzed
      the reduction of AcH to ethanol and the oxidation of NADH to NAD+, which occurred
      when gaseous AcH was applied to the ADH immobilized mesh that was wetted with a
      slightly acidic NADH solution. As NADH has an autofluorescence property [emission
      (lambdaem) at 490 nm; excitation (lambdaex) at 340 nm], the presence of gaseous
      AcH was visualized by a decrease of fluorescence of the NADH at the ADH
      immobilized mesh. After constructing the gaseous AcH imaging system,
      optimizations of pH, and concentration of the NADH solution were performed. As a
      result of the optimizations (500 MUM of NADH in 0.1 M of Tris hydrochloride (Tris
      HCl) buffer at pH 6.5), the AcH sniff-cam showed a wide dynamic range (0.1-10
      ppm) for gaseous AcH with a high correlation coefficient (R = 0.999).
      Furthermore, a fluorescence gradient with a rounded shape centered in a gas
      outlet was observed. These results demonstrated that the AcH sniff-cam utilizing
      the fluorescence decrease of NADH could be used to quantitatively evaluate the 2
      D distribution of gaseous AcH.

PMID- 28758644
TI  - SMRI Biomarkers Predict Electroconvulsive Treatment Outcomes: Accuracy with
      Independent Data Sets.
AB  - Owing to the rapid and robust clinical effects, electroconvulsive therapy (ECT)
      represents an optimal model to develop and test treatment predictors for major
      depressive disorders (MDDs), whereas imaging markers can be informative in
      identifying MDD patients who will respond to a specific antidepressant treatment
      or not. Here we aim to predict post-ECT depressive rating changes and remission
      status using pre-ECT gray matter (GM) in 38 MDD patients and validate in two
      independent data sets. Six GM regions including the right
      hippocampus/parahippocampus, right orbitofrontal gyrus, right inferior temporal
      gyrus (ITG), left postcentral gyrus/precuneus, left supplementary motor area, and
      left lingual gyrus were identified as predictors of ECT response, achieving
      accuracy of 89, 90 and 86% for remission prediction in three independent, age
      matched data sets, respectively. For MDD patients, GM density increases only in
      the left supplementary motor cortex and left postcentral gyrus/precuneus after
      ECT. These results suggest that treatment-predictive and treatment-responsive
      regions may be anatomically different but functionally related in the context of
      ECT response. To the best of our knowledge, this is the first attempt to
      quantitatively identify and validate the ECT treatment biomarkers using multi
      site GM data. We address a major clinical challenge and provide potential
      opportunities for more effective and timely interventions for electroconvulsive
      treatment.

PMID- 28758646
TI  - Reply to the 'Comment on "Proton transport in barium stannate: classical, semi
      classical and quantum regime"'.
AB  - We respond to the erroneous criticisms about our modeling of proton transport in
      barium stannate [G. Geneste et al., Phys. Chem. Chem. Phys., 2015, 17, 19104]. In
      this previous work, we described, on the basis of density-functional
      calculations, proton transport in the classical and semi-classical regimes, and
      provided arguments in favor of an adiabatic picture for proton transfer at low
      temperature. We re-explain here our article (with more detail and precision), the
      content of which has been distorted in the Comment, and reiterate our arguments
      in this reply. We refute all criticisms. They are completely wrong in the context
      of our article. Even though a few of them are based on considerations probably
      true in some metals, they make no sense here since they do not correspond to the
      content of our work. It has not been understood in the Comment that two
      competitive configurations, associated with radically different transfer
      mechanisms, have been studied in our work. It has also not been understood in the
      Comment that the adiabatic regime described for transfer occurs in the protonic
      ground state, in a very-low barrier configuration with the protonic ground state
      energy larger than the barrier. Serious confusion has been made in the Comment
      with the case of H in metals like Nb or Ta, leading to the introduction of the
      notion of (protonic) "excited-state proton transfer", relevant for H in some
      metals, but (i) that does not correspond to the (ground state) adiabatic
      transfers here described, and (ii) that does not correspond to what is commonly
      described as the "adiabatic limit for proton transfer" in the scientific
      literature. We emphasize, accordingly, the large differences between proton
      transfer in the present oxide and hydrogen jumps in metals like Nb or Ta, and the
      similarities between proton transfer in the present oxide and in acid-base
      solutions. We finally describe a scenario for proton transfer in the present
      oxide regardless of the temperature regime.

PMID- 28758647
TI  - Electrochemical behaviour at a liquid-organogel microinterface array of fucoidan
      extracted from algae.
AB  - Fucoidans are sulfated polysaccharides mostly derived from algae and used in a
      number of applications (e.g. nutrition, cosmetics, pharmaceuticals and
      biomaterials). In this study, the electrochemical behaviour of fucoidans
      extracted from two algal species (Undaria pinnatifida and Fucus vesiculosus) was
      assessed using voltammetry at an array of micro-interfaces formed between two
      immiscible electrolyte solutions (MUITIES) in which the organic electrolyte phase
      was gelled. Cyclic voltammetry revealed an adsorption process when scanning to
      negative potentials, followed by a desorption peak at ca. -0.50 V on the reverse
      scan, indicating the electroactivity of both fucoidans. U. pinnatifida fucoidan
      showed a more intense voltammetric signal compared to F. vesiculosus fucoidan. In
      addition, use of tridodecylmethylammonium (TDMA+) or tetradodecylammonium (TDDA+)
      as the organic phase electrolyte cation provided improved detection of both
      fucoidans relative to the use of bis(triphenylphosphoranylidene)ammonium (BTPPA+)
      cation. Application of adsorptive stripping voltammetry provided a linear
      response of current with fucoidan concentration in the range 2-20 MUg mL-1 for U.
      pinnatifida fucoidan (with TDMA+) and 10-100 MUg mL-1 for F. vesiculosus fucoidan
      (with TDDA+). The combination of TDMA+ in the organic phase and adsorptive pre
      concentration for 180 s afforded a detection limit of 1.8 MUg mL-1 fucoidan (U.
      pinnatifida) in aqueous phase of 10 mM NaOH and 2.3 MUg mL-1 in synthetic urine
      (pH adjusted). These investigations demonstrate the electroactivity of fucoidans
      at the MUITIES array and provide scope for their detection at low MUg mL-1
      concentrations using this approach.

PMID- 28758648
TI  - Shaping nanofiltration channels in a carbonaceous membrane via controlling the
      pyrolysis atmosphere.
AB  - This work investigates the effect of atmosphere on pyrolysis of a polymer matrix
      (precursor) for directing its transformation towards more disordered graphene
      species and smaller graphitic nanograins. These two structural characteristics
      are crucial to the generation of nano-channels (NCs) pertinent to nanofiltration
      (NF). Two measures are explored hereby to conduct the study: varying the
      pyrolysis atmosphere and implementing highly dispersed nickel atomic clusters (Ni
      clusters) in the coating matrix undergoing pyrolysis. A thermally reactive
      polymer precursor is developed to allow the above two measures to act more
      effectively. The various pyrolysis atmospheres employed include inert Ar, a
      reducing H2/N2 gas mixture, and weak oxidizing CO2. In the absence of the Ni
      clusters, the H2/N2 atmosphere restrains the extent of graphitization through a
      chain transfer effect of H2 that ceases the free radical chain propagation,
      whereas CO2, owing to its high critical temperature (Tc) nature, shows the
      capability to reduce nanograin sizes. As for the catalytic roles of the embedded
      Ni-clusters, they vary with the pyrolysis atmosphere applied: offering coke
      nuclei for the growth of carbonaceous grains in Ar, enhancing gasification of
      carbon in CO2, and repressing the extent of aromatization via hydrogenation in
      H2/N2. The carbonaceous membranes (CnMs) obtained under the above pyrolysis
      conditions are distinguished by the distribution density and structure of NCs
      evolved, which locate primarily in the boundaries of nanograins. The NF of an
      aqueous solution of methylene blue (MB, 10 ppmw) is utilized to assess these CnMs
      to show impacts of the NCs on the separation performance.

PMID- 28758649
TI  - Evidence for differentiated ionic and surface contact effects driving bacterial
      inactivation by way of genetically modified bacteria.
AB  - New evidence is presented for the bacterial inactivation of E. coli presenting
      normal porins on sputtered Ag-Cu surfaces compared with similar E. coli porinless
      bacteria. Inactivation at a reduced rate was observed on the genetically modified
      porinless bacteria interacting via surface contact with metal/oxides without the
      intervention of metal-ions.

PMID- 28758650
TI  - Pushing the limits of automated glycan assembly: synthesis of a 50mer
      polymannoside.
AB  - Automated glycan assembly (AGA) enables rapid access to oligosaccharides. The
      overall length of polymers created via automated solid phase synthesis depends on
      very high yields at every step to obtain full length products. The synthesis of
      long polymers serves as the ultimate test of the efficiency and reliability of
      synthetic processes. A series of Man-(1 -> 6)-alpha-Man linked oligosaccharides
      up to a 50mer, the longest synthetic sequence yet assembled from monosaccharides,
      has been realized via a 102 step synthesis. We identified a suitable mannose
      building block and applied a capping step in the final five AGA cycles to
      minimize (n - 1) deletion sequences that are otherwise difficult to remove by
      HPLC.

PMID- 28758651
TI  - Analytical approaches to study domain formation in biomimetic membranes.
AB  - Domains in biological membranes are linked to a range of biochemical life
      functions and thus understanding the fundamental physico-chemical drivers of
      domain formation is one of the key problems of biophysics and chemical biology.
      The phospholipid bilayer that is the structural basis of the biomembrane is a
      complex multicomponent mixture, and hence domain formation may be the result of
      thermodynamic phase equilibria, or specific sequestration of certain lipids;
      possibly both. There are several obstacles in the way of studying domains and
      thermodynamic phases in biomembranes: the complexity of the lipid mixture, the
      two dimensional nature of the membrane and the variety of superstructures the
      lipid membrane can fold into. Complexity is addressed by the introduction of
      biomimetic membranes, simplified mixtures of synthetic lipids. Most studies of
      lipid phase equilibria have been conducted using a biomimetic membrane. This
      review is intended to address the challenges posed to analytical methodology by
      the membrane dimensions, while also discussing the question of the reference
      state. Four key methods are assessed for their strengths and weaknesses in
      identifying domains and thermodynamic phases in membranes: differential scanning
      calorimetry, fluorescence microscopy, atomic force microscopy and quartz crystal
      microbalance. It is demonstrated that, while these methods provide complementary
      information and thus should be used in tandem, quartz crystal microbalance based
      nano-viscosimetry measurements offer a breakthrough in measuring phase transition
      temperatures, and allow the compilation of phase diagrams, of single bilayers of
      lipid mixtures. By comparing the structural phases of the lipids used for the
      different methods, it is also shown that the membrane curvature in vesicular
      lipid samples inhibits the formation of domains which are only observed in flat
      lamellar membranes, or giant unilamellar liposomes where the role of curvature is
      negligible.

PMID- 28758652
TI  - Metallomics: the history over the last decade and a future outlook.
AB  - In 2004, the term "metallomics" was coined to describe integrated biometal
      science (H. Haraguchi, Metallomics as Integrated Biometal Science, J. Anal. At.
      Spectrom., 2004, 19, 5-14). Around 10 years have passed since then, and the
      history of metallomics over the last decade is reviewed here, discussing the
      development of metallomics before and after the proposal. Furthermore, the future
      outlook of metallomics research will be considered, in terms of topics such as
      the organization of platforms for metallomics research related to trace metal
      sciences, a simplified model of the biological system and omics-sciences,
      research subjects in metallomics, recent trends of metallomics research, and the
      challenge of single biological cell analysis.

PMID- 28758653
TI  - A rhodium-catalyzed tandem reaction of N-sulfonyl triazoles with indoles: access
      to indole-substituted indanones.
AB  - An efficient strategy for the synthesis of structurally diverse indole
      substituted indanones via a rhodium(ii)-catalyzed tandem reaction of N
      sulfonyltriazoles with indoles was developed. The reaction involves rhodium(ii)
      catalyzed denitrogenation of the N-sulfonyltriazoles to form an oxonium ylide,
      followed by nucleophilic addition of the indoles and subsequent skeletal
      rearrangement. This strategy provides straightforward access to indanone
      frameworks bearing quaternary carbon centers.

PMID- 28758654
TI  - Particle size affects the cytosolic delivery of membranotropic peptide
      functionalized platinum nanozymes.
AB  - Delivery of therapeutic agents inside the cytosol, avoiding the confinement in
      endo-lysosomal compartments and their degradative environment, is one of the key
      targets of nanomedicine to gain the maximum remedial effects. Current approaches
      based on cell penetrating peptides (CPPs), despite improving the cellular uptake
      efficiency of nanocarriers, have shown controversial results in terms of
      intracellular localization. To elucidate the delivery potential of CPPs, in this
      work we analyzed the role of the particle size in influencing the ability of a
      membranotropic peptide, namely gH625, to escape the endo-lysosomal pathway and
      deliver the particles in the cytosol. To this aim, we carried out a systematic
      assessment of the cellular uptake and distribution of monodisperse platinum
      nanoparticles (PtNPs), having different diameters (2.5, 5 and 20 nm) and citrate
      capping or gH625 peptide functionalization. The presence of gH625 significantly
      increased the amount of internalized NPs in human cervix epithelioid carcinoma
      cells, as a function of particle size. However, scanning transmission electron
      microscopy (STEM) and electron tomography (ET) revealed a prevalent confinement
      of PtNPs within vesicular structures, regardless of the particle size and surface
      functionalization. Only in the case of the smallest 2.5 nm particles, the
      membranotropic peptide was able to partly maintain its functionality, enabling
      cytosolic delivery of a small fraction of internalized PtNPs, though particle
      agglomeration in culture medium limited single-particle transport across the cell
      membrane. Interestingly, membrane crossing by 2.5 nm functionalized-PtNPs seemed
      to occur by diffusion through the lipid bilayer, with no apparent membrane
      damage. For larger particle sizes (>=5 nm), their hindrance likely blocked the
      membranotropic mechanism. Combining the enhanced uptake and partial cytosolic
      delivery promoted by gH625, we were able to achieve a strong improvement of the
      antioxidant nanozyme function of 2.5 nm PtNPs, decreasing both the endogenous ROS
      level and its overproduction following an external oxidative insult.

PMID- 28758655
TI  - Inhibitors of nicotinamide N-methyltransferase designed to mimic the methylation
      reaction transition state.
AB  - Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyses the
      methylation of nicotinamide to form N'-methylnicotinamide. Both NNMT and its
      methylated product have recently been linked to a variety of diseases, suggesting
      a role for the enzyme as a therapeutic target beyond its previously ascribed
      metabolic function in detoxification. We here describe the systematic development
      of NNMT inhibitors derived from the structures of the substrates involved in the
      methylation reaction. By covalently linking fragments of the NNMT substrates a
      diverse library of bisubstrate-like compounds was prepared. The ability of these
      compounds to inhibit NNMT was evaluated providing valuable insights into the
      structural tolerances of the enzyme active site. These studies led to the
      identification of new NNMT inhibitors that mimic the transition state of the
      methylation reaction and inhibit the enzyme with activity on par with established
      methyltransferase inhibitors.

PMID- 28758656
TI  - Magnetization reversal in circular vortex dots of small radius.
AB  - We present a detailed study of the magnetic behavior of Permalloy (Ni80Fe20
      alloy) circular nanodots with small radii (30 nm and 70 nm) and different
      thicknesses (30 nm or 50 nm). Despite the small size of the dots, the measured
      hysteresis loops manifestly display the features of classical vortex behavior
      with zero remanence and lobes at high magnetic fields. This is remarkable because
      the size of the magnetic vortex core is comparable to the dot diameter, as
      revealed by magnetic force microscopy and micromagnetic simulations. The dot
      ground states are close to the border of the vortex stability and, depending on
      the dot size, the magnetization distribution combines attributes of the typical
      vortex, single domain states or even presents features resembling magnetic
      skyrmions. An analytical model of the dot magnetization reversal, accounting for
      the large vortex core size, is developed to explain the observed behavior,
      providing a rather good agreement with the experimental results. The study
      extends the understanding of magnetic nanodots beyond the classical vortex
      concept (where the vortex core spins have a negligible influence on the magnetic
      behavior) and can therefore be useful for improving emerging spintronic
      applications, such as spin-torque nano-oscillators. It also delimits the
      feasibility of producing a well-defined vortex configuration in sub-100 nm dots,
      enabling the intracellular magneto-mechanical actuation for biomedical
      applications.

PMID- 28758657
TI  - Interactions between silica particles in the presence of multivalent coions.
AB  - Forces between charged silica particles in solutions of multivalent coions are
      measured with colloidal probe technique based on atomic force microscopy. The
      concentration of 1 : z electrolytes is systematically varied to understand the
      behavior of electrostatic interactions and double-layer properties in these
      systems. Although the coions are multivalent the Derjaguin, Landau, Verwey, and
      Overbeek (DLVO) theory perfectly describes the measured force profiles. The
      diffuse-layer potentials and regulation properties are extracted from the forces
      profiles by using the DLVO theory. The dependencies of the diffuse-layer
      potential and regulation parameter shift to lower concentration with increasing
      coion valence when plotted as a function of concentration of 1 : z salt.
      Interestingly, these profiles collapse to a master curve if plotted as a function
      of monovalent counterion concentration.

PMID- 28758658
TI  - Exploring the chemistry of backbone amino(chloro)phosphanyl-substituted imidazole
      2-thiones.
AB  - Backbone (R'2N)2P-substituted imidazole-2-thiones 2a-c [(R'2N)2P-IMSR,R; IMSR,R =
      1,3-dialkylimidazole-2-thione-4-yl, a: R = iPr, R' = Et; b: R = Mes, R' = Et, c:
      R = Me, R' = iPr] were treated with PCl3 to synthesize R'2N(Cl)P-substituted
      imidazole-2-thiones 3a-c [R'2N(Cl)P-IMSR,R]. The P-chloro compounds 3a,b were
      used to explore the chemistry further, i.e. nucleophilic substitution at
      phosphorus using Ph2CHLi or fluorenyl lithium afforded compounds 4a-c [R'2N(R'')P
      IMSR,R; a: R = iPr, R' = Et, R'' = PH2CH; b: R = Mes, R' = Et, R'' = Flu c: R =
      iPr, R' = Et, R'' = Flu]. Compound 4c was used to access the P-borane adduct 5
      [R'2N(R'')(BH3)P-IMSR,R; R = iPr, R' = Et, R'' = Flu] and phosphinoyl-substituted
      imidazolium hydrogensulfate 6 [[R'2N(R'')(O)P-IMHR,R]HSO4; IMHR,R = 1,3
      dialkylimidazolium-4-yl, R = iPr, R' = Et, R'' = Flu]. Compounds 4a,b were
      transformed into the P-Cl compounds 7a,b [R''(Cl)P-IMSR,R; a: R = iPr, R'' =
      Ph2CH; b: R = Mes, R'' = Flu] which represent potential starting materials for
      backbone phosphaalkenyl substituted imidazole-2-thiones. Compound 7a yielded the
      NHC-stabilized phosphenium salt 8 [[R''(IMe4)P-IMSR,R]Cl; R = iPr, R' = Et, R'' =
      Ph2CH, IMe4 = 1,3,4,5-tetramethylimidazole-2-ylidene] in reaction with 1,3,4,5
      tetramethylimidazole-2-ylidene (IMe4). Attempts to deprotonate 7a,b using nBuLi
      revealed that nucleophilic substitution of P-Cl to give the P-nBu product
      occurred preferentially, and dehydrochlorination to the phosphaalkene was not
      observed.

PMID- 28758659
TI  - Capillary uptake in macroporous compressible sponges.
AB  - The capillarity-driven uptake of liquid in swellable, highly porous sponges is of
      significant industrial importance. Sponges prepared using polymers and their
      composites with carbon nanotubes and graphene have been reported, with
      extraordinary solvent uptake capacities and with the ability to separate oil from
      water. However, the effect of systematic variation of sponge characteristics on
      solvent uptake has not been investigated. Here, we report experiments that study
      capillary uptake in a variety of flexible, centimetre-sized macroporous
      cylindrical sponges. We used ice-templating to prepare a series of model
      macroporous sponges in which the porosity, modulus and composition were
      systematically varied. We investigated two kinds of sponge: (a) those composed
      purely of cross-linked polymers and (b) those prepared as composites of inorganic
      particles and polymers. Both kinds of sponge are flexible and exhibit elastic
      recovery after large compressive deformation. All sponges were characterized
      thoroughly with respect to their pore microstructure and elastic modulus. When
      one end of a sponge is plunged into a large reservoir, water rises through
      capillary action against gravity. We observed a transition from an inertial
      capillary regime, where the liquid column height rose linearly with time, t, to a
      viscous capillary regime, where the liquid height rose with time t0.5. We showed
      that these results can be rationalized using analyses developed for rigid
      sponges. We combined differential momentum balance equations for uptake in rigid
      capillaries with the phenomenological Ergun-Forchheimer relations to account for
      the effect of the sponge microstructure. This approach works remarkably well in
      the viscous capillary regime and shows that capillary uptake is governed
      primarily by the total porosity and pore dimensions of soft sponges.

PMID- 28758660
TI  - Dielectrophoretic assembly of dimpled colloids into open packing structures.
AB  - Reversible solid-state phase transitions between open- and close-packed
      structures in two-dimensional colloidal crystals comprising 1.8 MUm dimpled
      spherical colloids were observed using negative dielectrophoresis. These
      asymmetrically-shaped colloids adopted lattices with cmm plane group symmetry and
      a packing fraction, phi, of 0.68 at low electric field strengths. At high
      electric field strengths, the close-packed p6m symmetry was observed, with phi =
      0.90. The transition between open and close-packed structures was found to be
      reversible, depending on the applied electric field strength and frequency.
      Finite Fourier transform analysis and COMSOL simulations revealed the existence
      of repulsive interactions between colloids perpendicular to the electric field
      lines due to a concentration of the electric field at the edges of the dimpled
      regions of the colloids. The repulsive interactions resulted in a stretching of
      the hexagonal lattice perpendicular to the electric field lines, the magnitude of
      which depended on the electric field strength. By screening the colloids from the
      electric field in local potential wells, the entropically favored close-packed
      hexagonal lattice with phi = 0.91 was recovered.

PMID- 28758661
TI  - Interpenetration of CH3NH3PbI3 and TiO2 improves perovskite solar cells while
      TiO2 expansion leads to degradation.
AB  - Perovskite solar cells have drawn much attention and achieved efficiencies over
      22%, but relatively little is known about the long-term stability under
      photovoltaic operation. So far, stability studies have reported about the
      importance of degradation of each layer, but little to no consideration has been
      given to the whole device architecture. We investigated the stability of
      perovskite solar cells in order to fundamentally understand the mechanism behind
      efficiency improvement/degradation during device operation. We found that during
      operation the interfaces of the perovskite and the electron-transport layer
      (ETL), meso-porous TiO2, further intermix with each other, which leads to
      improved power conversion efficiency (PCE) during the initial operation of these
      solar cells. The operation-induced structural changes are examined directly by X
      ray photoelectron spectroscopy (XPS) with in situ low-energy Ar+ sputtering and
      time-of-flight secondary ion mass spectrometry (ToF-SIMS) with C60 sputtering. In
      addition, this study describes that the primary cause of irreversible degradation
      during operation is due to the expansion of TiO2 and ion migration throughout the
      perovskite solar cell.

PMID- 28758662
TI  - The role of carbonate in electro-catalytic water oxidation by using Ni(1,4,8,11
      tetraazacyclotetradecane)2.
AB  - NiLi2+ are good electro-catalysts for water oxidation in phosphate or carbonate
      buffers. The results point out that the active oxidizing agents are L(X)NiIVOH4
      (3-n+1)/(2-n+1), where X = PO4Hn(3-n)- or CO3Hn(2-n)- formed from LNiIVX2via a
      mechanism involving an acid catalyzed O-P or O-C bond heterolysis. Carbonate
      behaves differently from phosphate as it is a non-innocent ligand and it can be
      oxidized.

PMID- 28758663
TI  - Correction: Dependence of gold nanoparticle radiosensitization on cell geometry.
AB  - Correction for 'Dependence of gold nanoparticle radiosensitization on cell
      geometry' by Wonmo Sung, et al., Nanoscale, 2017, 9, 5843-5853.

PMID- 28758664
TI  - Structural relaxation, viscosity, and network connectivity in a hydrogen bonding
      liquid.
AB  - In liquids, the ability of neighboring molecules to rearrange and jostle past
      each other is directly related to viscosity, the property which describes the
      propensity to flow. The presence of hydrogen bonds (H-bonds) complicates the
      molecular scale picture of viscosity. H-Bonds are attractive, directional
      interactions between molecules which, in some cases, result in transient network
      structures. In this work, we use experimental and computational methods to
      demonstrate that the timescale of H-bond network reorganization is the dominant
      dynamical timescale associated with viscosity for the case of the model H-bonding
      liquid n-methylacetamide (NMA). This molecule is a peptide analog which forms a
      transient linear H-bond network. Individual H-bond lifetimes and dynamical
      fluctuations were observed on the timescale of 1.5 ps, while collective motions
      and the longest lived population of H-bond partner lifetimes were observed on the
      order of 20 ps, in agreement with the Maxwell relaxation time. This identifies a
      mechanism which may aid in understanding the emergence of various complex
      phenomena arising from transient molecular structures, with implications ranging
      from the internal dynamics of proteins, to the glass transition, to better
      understanding the origins of the unique properties of H-bonding liquids.

PMID- 28758665
TI  - The length but not the sequence of peptide linker modules exerts the primary
      influence on the conformations of protein domains in cellulosome multi-enzyme
      complexes.
AB  - Cellulosomes are large multi-protein catalysts produced by various anaerobic
      microorganisms to efficiently degrade plant cell-wall polysaccharides down into
      simple sugars. X-ray and physicochemical structural characterisations show that
      cellulosomes are composed of numerous protein domains that are connected by
      unstructured polypeptide segments, yet the properties and possible roles of these
      'linker' peptides are largely unknown. We have performed coarse-grained and all
      atom molecular dynamics computer simulations of a number of cellulosomal linkers
      of different lengths and compositions. Our data demonstrates that the effective
      stiffness of the linker peptides, as quantified by the equilibrium fluctuations
      in the end-to-end distances, depends primarily on the length of the linker and
      less so on the specific amino acid sequence. The presence of excluded volume -
      provided by the domains that are connected - dampens the motion of the linker
      residues and reduces the effective stiffness of the linkers. Simultaneously, the
      presence of the linkers alters the conformations of the protein domains that are
      connected. We demonstrate that short, stiff linkers induce significant
      rearrangements in the folded domains of the mini-cellulosome composed of
      endoglucanase Cel8A in complex with scaffoldin ScafT (Cel8A-ScafT) of Clostridium
      thermocellum as well as in a two-cohesin system derived from the scaffoldin ScaB
      of Acetivibrio cellulolyticus. We give experimentally testable predictions on
      structural changes in protein domains that depend on the length of linkers.

PMID- 28758666
TI  - MALDI MS imaging investigation of the host response to visceral leishmaniasis.
AB  - Mass spectrometry imaging (MSI) of animal tissues has become an important tool
      for in situ molecular analyses and biomarker studies in several clinical areas,
      but there are few applications in parasitological studies. Leishmaniasis is a
      neglected tropical disease, and experimental mouse models have been essential to
      evaluate pathological and immunological processes and to develop diagnostic
      methods. Herein we have employed MALDI MSI to examine peptides and low molecular
      weight proteins (2 to 20 kDa) differentially expressed in the liver during
      visceral leishmaniasis in mice models. We analyzed liver sections of Balb/c mice
      infected with Leishmania infantum using the SCiLS Lab software for statistical
      analysis, which facilitated data interpretation and thus highlighted several key
      proteins and/or peptides. We proposed a decision tree classification for visceral
      leishmaniasis with distinct phases of the disease, which are named here as
      healthy, acute infection and chronic infection. Among others, the ion of m/z 4963
      was the most important to identify acute infection and was tentatively identified
      as Thymosin beta4. This peptide was previously established as a recovery factor
      in the human liver and might participate in the response of mice to Leishmania
      infection. This preliminary investigation shows the potential of MALDI MSI to
      complement classical compound selective imaging techniques and to explore new
      features not yet recognized by these approaches.

PMID- 28758667
TI  - Reciprocal upregulation of scavenger receptors complicates interpretation of
      nanoparticle uptake in non-phagocytic cells.
AB  - Nanoparticles have great potential as drug delivery vehicles or as imaging agents
      for treatment and diagnosis of various diseases. It is therefore crucial to
      understand how nanoparticles are taken up by cells, both phagocytic and non
      phagocytic. Small interference RNA has previously been used to isolate the effect
      of particular receptors in nanoparticle uptake by silencing their expression.
      Here we show that, when it comes to receptors with overlapping function,
      interpretation of such data has to be done with caution. We followed the uptake
      of silica nanoparticles by scavenger receptors in A549 lung epithelial cells.
      While we successfully knocked-down gene expression of several different receptors
      within the scavenger receptor family (SR-A1, MARCO, SR-BI, LOX-1 and LDLR) this
      caused reciprocal up and down regulation of the other scavenger receptors.
      Subsequent nanoparticle uptake experiments in silenced cells exhibit a complex
      behaviour, which could easily be misinterpreted if reciprocal regulation is not
      considered. Preliminary identification of the actual scavenger receptors involved
      can be found by disentangling the effects mathematically. Finally, we show that
      the effects are still present under more realistic biological conditions, namely
      at higher serum concentrations.

PMID- 28758668
TI  - A subphthalocyanine-pyrene dyad: electron transfer and singlet oxygen generation.
AB  - A light harvesting subphthalocyanine-pyrene dyad has been synthesized and
      characterized by linking pyrene (Py) with subphthalocyanine (SubPc) at its axial
      position with the B-O bond through the para position of the benzene group. Upon
      photoexcitation at the pyrene unit of the dyad, an efficient electron transfer
      from the singlet-excited state of Py to SubPc was observed. The electron transfer
      features were also observed by exciting the SubPc entity, but with slower rates
      (~108 s-1). From the electrochemical measurements, the negative driving forces
      for charge separation via both the singlet states of Py and SubPc in the polar
      solvents indicate that the electron transfer is thermodynamically feasible.
      Interestingly, the examined compounds showed relatively high efficiency for
      producing the singlet oxygen (PhiDelta = ~0.70). The collected data suggested the
      usefulness of the examined subphthalocyanine-pyrene dyad as a model of light
      harvesting system, as well as a sensitizer for photodynamic therapy.

PMID- 28758669
TI  - DOTA analogues with a phosphinate-iminodiacetate pendant arm: modification of the
      complex formation rate with a strongly chelating pendant.
AB  - The new ligand H6do3aPida combines the macrocyclic DOTA-like cavity and the open
      chain iminodiacetate group connected through a coordinating phosphinate spacer.
      Its acid-base and coordination properties in solution were studied by
      potentiometry. Thermodynamic coordination characteristics of both chelating units
      are similar to those reported for H4dota and iminodiacetic acid themselves,
      respectively, so, macrocyclic and iminodiacetate units behave independently. The
      formation kinetics of the Ce(iii)-H6do3aPida complex was studied by UV-Vis
      spectrophotometry. Various out-of-cage intermediates were identified with 1 : 1,
      1 : 2 and 2 : 1 ligand-to-metal ratios. The presence of the strongly coordinating
      iminodiacetate group significantly slows down the metal ion transfer into the
      macrocyclic cavity and, so, the formation of the in-cage complex is two orders of
      magnitude slower than that reported for the Ce(iii)-H4dota system. The kinetic
      inertness of the [Ce(do3aPida)]3- complex towards acid-assisted dissociation is
      comparable to that of the [Ce(dota)]- complex. The coordination modes of the
      ligand are demonstrated in the solid-state structure of
      [Cu4(do3aPida)(OH)(H2O)4]Cl.7.5H2O.

PMID- 28758670
TI  - Stepwise construction of discrete parallelogram- and prism-shaped organometallic
      architectures based on half-sandwich rhodium fragments.
AB  - Herein we describe how to take advantage of a multifunctional ligand to
      conveniently control the shapes and sizes of different types of discrete
      organometallic assemblies. Using a versatile ligand 2-(pyridin-2-yl)-1H-imidazole
      4,5-dicarboxylate (HL2-), which features three kinds of chelating sites, together
      with half-sandwich rhodium fragments, a series of discrete organometallic
      complexes with tetranuclear parallelogram and hexanuclear trigonal prism shapes
      were achieved. The isomerization of the hexanuclear assemblies was confirmed by
      single-crystal X-ray diffraction analysis. The results also reiterate that
      pyridyl-substituted imidazole-4,5-dicarboxylate ligands can be used as
      multifunctional organic scaffolds in the construction of elegant architectures.

PMID- 28758671
TI  - Switchable changes in the conductance of single-walled carbon nanotube networks
      on exposure to water vapour.
AB  - We have discovered that wrapping single-walled carbon nanotubes (SWCNTs) with
      ionic surfactants induces a switch in the conductance-humidity behaviour of SWCNT
      networks. Residual cationic vs. anionic surfactant induces a respective increase
      or decrease in the measured conductance across the SWCNT networks when exposed to
      water vapour. The magnitude of this effect was found to be dependent on the
      thickness of the deposited SWCNT films. Previously, chemical sensors, field
      effect transistors (FETs) and transparent conductive films (TCFs) have been
      fabricated from aqueous dispersions of surfactant functionalised SWCNTs. The
      results reported here confirm that the electrical properties of such components,
      based on randomly orientated SWCNT networks, can be significantly altered by the
      presence of surfactant in the SWCNT layer. A mechanism for the observed behaviour
      is proposed based on electrical measurements, Raman and UV-Vis-NIR spectroscopy.
      Additionally, the potential for manipulating the sensitivity of the surfactant
      functionalised SWCNTs to water vapour for atmospheric humidity sensing was
      evaluated. The study also presents a simple method to establish the effectiveness
      of surfactant removal techniques, and highlights the importance of characterising
      the electrical properties of SWCNT-based devices in both dry and humid operating
      environments for practical applications.

PMID- 28758672
TI  - Stress sensitivity as a putative mechanism linking childhood trauma and
      psychopathology in youth's daily life.
AB  - OBJECTIVE: Childhood trauma (CT) is associated with a range of psychopathologies,
      including psychosis. However, evidence on underlying mechanisms remains limited.
      The study aimed to investigate whether CT impacts on youth mental health by
      modifying sensitivity to stress in daily life. METHOD: The experience sampling
      method (ESM) was used to measure momentary stress, negative affect and psychotic
      experiences in 99 adolescents and young adults (43 help-seeking service users, 16
      siblings and 40 controls). Before ESM assessments, CT and depressive, anxiety and
      psychotic symptoms were assessed. RESULTS: Stress sensitivity, that is, the
      association between momentary stress and (i) negative affect and (ii) psychotic
      experiences, was modified by physical and emotional abuse and, partially,
      emotional and physical neglect, but not sexual abuse in service users and
      controls. While there was strong evidence for increased stress sensitivity in
      service users when high vs. low levels of CT were compared, a pattern of
      resilience was evident in controls, with attenuated, or no differences in, stress
      sensitivity in those with high vs. low CT levels. Less consistent findings were
      observed in siblings. CONCLUSIONS: Stress sensitivity may be an important risk
      and resilience mechanism through which CT impacts on mental health in youth.

PMID- 28758673
TI  - Return to work predictors after traumatic brain injury in a welfare state.
AB  - OBJECTIVE: To identify predictors of return to work (RTW) and stable labour
      market attachment (LMA) after severe traumatic brain injury (TBI) in Denmark.
      MATERIALS & METHODS: Patients aged 18-64 years, admitted to highly specialized
      neurorehabilitation after severe TBI 2004-2012 were included and followed up for
      <=6 years. Weekly LMA data were retrieved from a national register of public
      assistance benefits. Weeks without or with supplemental public assistance
      benefits were defined as LMA weeks. Time of RTW was defined as first week with
      LMA. Stable LMA was defined as weeks with LMA >=75% first year after RTW.
      Multivariable regressions were used to identify predictors of RTW and stable LMA
      among preinjury characteristics, injury severity, functional ability and
      rehabilitation trajectories. RESULTS: For the analyses of RTW and stable LMA, 651
      and 336 patients were included, respectively. RTW was significantly associated
      with age (adjusted subhazard ratio 0.98, 95% CI 0.97-0.99), education (1.83, 95%
      CI 1.16-2.89), supplemental benefits (3.97, 95% CI 2.04-7.71), no benefits (4.86,
      95% CI 2.90-8.17), length of stay in acute care (0.77, 95% CI 0.60-0.99) and time
      period of injury (1.56, 95% CI 1.15-2.10). The only significant predictor of
      stable LMA was age (adjusted odds ratio 0.97, 95% CI 0.95-0.99). CONCLUSION: RTW
      after severe TBI was associated with several socio-economic factors, whereas
      maintaining LMA depended on age only. We suggest that RTW rates could be improved
      by extensive rehabilitation targeting people that are older and low-educated, as
      these were less likely to RTW.

PMID- 28758674
TI  - Regulation of fluid flow through the mammary gland of dairy cows and its effect
      on milk production: a systematic review.
AB  - Dairy milk consists of more than 85% water. Therefore, understanding the
      regulation of fluid absorption in the mammary gland is relevant to improving milk
      production. In recent decades, studies using different approaches, including
      blood flow, transmembrane fluid flow, tight junction, fluid flow of the
      paracellular pathway and functional mammary epithelial cell state, have been
      conducted aiming to investigate how mammary gland fluid absorption is regulated.
      However, the relationship between regulation mechanisms of fluid flow and milk
      production has not been studied systematically. The present review summarizes a
      series of key milk yield regulatory factors mediated by whole-mammary fluid flow,
      including milk, mammary blood flow, blood/tissue fluid-cell fluid flow and cell
      alveolus fluid flow. Whole-mammary fluid flow regulates milk production by
      altering transporter activity, ion channels, local microcirculation-related
      factors, driving force of fluid transport (osmotic pressure or electrochemical
      gradient), cellular connection state and a cell volume sensitive mechanism. In
      addition, whole-mammary fluid flow plays important roles in milk synthesis and
      secretion. Knowledge gained from fluid flow-mediated regulatory mechanisms of the
      dairy mammary gland will lead to a fundamental understanding of lactation biology
      and will be beneficial for the improvement of dairy productivity. (c) 2017
      Society of Chemical Industry.

PMID- 28758675
TI  - Meeting after meeting: 20 years of discoveries by the members of the Exocytosis
      Endocytosis Club.
AB  - Twenty years ago, a group of French cell biologists merged two scientific clubs
      with the aim of bringing together researchers in the fields of Endocytosis and
      Exocytosis. Founded in 1997, the first annual meeting of the Exocytosis Club was
      held in 1998. The Endocytosis Club held quarterly meetings from its founding in
      1999. The first joint annual meeting of the Exocytosis-Endocytosis Club took
      place in Paris in April, 2001. What started as a modest gathering of enthusiastic
      scientists working in the field of cell trafficking has gone from strength to
      strength, rapidly becoming an unmissable yearly meeting, vividly demonstrating
      the high quality of science performed in our community and beyond. On the
      occasion of the 20th meeting of our club, we want to provide historic insight
      into the fields of exocytosis and endocytosis, and by extension, to subcellular
      trafficking, highlighting how French scientists have contributed to major
      advances in these fields. Today, the Exocytosis-Endocytosis Club represents a
      vibrant and friendly community that will hold its 20th meeting at the Presqu'Ile
      de Giens, near Toulon in the South of France, on May 11-13, 2017.

PMID- 28758676
TI  - Assessment and genetic analysis of heavy metal content in rice grain using an
      Oryza sativa * O. rufipogon backcross inbred line population.
AB  - BACKGROUND: Heavy metal accumulation in rice is a growing concern for public
      health. Backcross inbred lines derived from an interspecific cross of Oryza
      sativa * O. rufipogon were grown in two distinct ecological locations (Hangzhou
      and Lingshui, China). The objective of this study was to characterise the
      contents of heavy metal in rice grains, and to identify quantitative trait loci
      (QTLs) for heavy metal contents. RESULTS: The contents of Ni, As, Pb, Cr and Hg
      in milled rice showed a significant decline as compared with those in brown rice,
      whereas the content of Cd showed little change. The concentration of heavy metal
      in rice grain varied greatly between the two environments. A total of 24 QTLs
      responsible for heavy metal contents were detected, including two for both the
      brown and milled rice, 13 for brown rice only, and nine for milled rice only. All
      the QTLs except two had the enhancing alleles derived from O. rufipogon. Sixteen
      QTLs were clustered in six chromosomal regions. CONCLUSION: Environmental
      variation plays an important role in the heavy metal contents in rice grain. QTLs
      detected in this study might be useful for breeding rice varieties with low heavy
      metal content. (c) 2017 Society of Chemical Industry.

PMID- 28758677
TI  - A simple method to estimate the isoelectric point of modified Tomato bushy stunt
      virus (TBSV) particles.
AB  - We present a simple method to estimate the isoelectric point (pI) of Tomato Bushy
      Stunt particles. We demonstrate that the combination of agarose gels with
      different pH buffers can be used to electrophorese the virus particles and their
      migration patterns can be compared. This method allows us to estimate the pI of
      the virus particles (wild type, wt, and genetically modified particles) and to
      monitor the effect of the pI of modified peptide side chains of the viral capsid
      subunit on the pI of the whole virus particle.

PMID- 28758678
TI  - Polymethacrylate-based monoliths as stationary phases for separation of
      biopolymers and immobilization of enzymes.
AB  - The experiences in the production and application of polymethacrylate-based
      monolithic supports, since their development almost thirty years ago, are
      presented. The main driving force for the development of new chromatographic
      supports was the necessity for the isolation and separation of physiologically
      active biopolymers and their use for therapeutic purposes. For this sake, a
      development of a method for fast separation, preventing denaturation and
      preserving their biological activity was necessary. Development of polysaccharide
      based supports, followed by the introduction of polymer-based chromatographic
      media, is shortly described. This development was followed by the advances in
      monolithic media that are now used for both large- and small-scale separation of
      biopolymers and nanoparticles. Finally, a short overview is given about the
      applications of monoliths for sample displacement chromatography, resulting in
      isolation of physiologically active biomolecules, such as proteins, protein
      complexes, and nucleic acid, as well as high-throughput sample preparation for
      proteomic investigations.

PMID- 28758680
TI  - All interventions are complex, but some are more complex than others: using
      iCAT_SR to assess complexity.

PMID- 28758679
TI  - Water stress and ripeness effects on the volatile composition of Cabernet
      Sauvignon wines.
AB  - BACKGROUND: Controlled water deficits affect grape berry physiology and the
      resulting wines, with volatile composition being the one of the affected
      parameters. However, there is a potential disconnect between aromatic maturity
      and sugar accumulation. Accordingly, the effects of three different water status
      levels over two growing seasons (2014 and 2015) and two different harvest dates
      on the aroma compounds from Cabernet Sauvignon wines were studied. Volatile
      compounds were determined using headspace solid phase microextraction coupled
      with gas chromatoghraphy/mass spectrometry. RESULTS: Around 45 volatile compounds
      were determined in the wines and, among these, esters were affected the most,
      presenting lower concentrations when the most restrictive water treatment was
      applied in both years. By contrast, volatile acids presented the highest
      concentrations when the lowest level of irrigation was applied. On the other
      hand, a delay in harvesting produced an increase in the total amount of volatile
      compounds in samples from the most restrictive water treatment. These results are
      coincident with a principal component analysis that indicated a great separation
      between years, deficit irrigation treatments and harvest dates. CONCLUSION: The
      results of the present study suggest that a low water supply had a negative
      effect on the aromatic potential of wines at a similar ripening stage. However,
      this effect could be countered by harvesting at a later date. (c) 2017 Society of
      Chemical Industry.

PMID- 28758682
TI  - Ten implementations of ptychography.
AB  - Ptychography is an increasingly popular phase retrieval imaging technique, able
      to routinely deliver quantitative phase images with extended field of view at
      diffraction limited resolution. Different variants of this technique, like Bragg
      ptychography and Fourier ptychography, have also been developed and applied to
      various fields. Here we experimentally demonstrate 10 ways to implement the
      conventional real space transmission ptychography, and compare their properties
      to provide a guide to choosing the optimal setup for a specific application.

PMID- 28758681
TI  - High-resolution synchrotron imaging shows that root hairs influence rhizosphere
      soil structure formation.
AB  - In this paper, we provide direct evidence of the importance of root hairs on pore
      structure development at the root-soil interface during the early stage of crop
      establishment. This was achieved by use of high-resolution (c. 5 MUm) synchrotron
      radiation computed tomography (SRCT) to visualise both the structure of root
      hairs and the soil pore structure in plant-soil microcosms. Two contrasting
      genotypes of barley (Hordeum vulgare), with and without root hairs, were grown
      for 8 d in microcosms packed with sandy loam soil at 1.2 g cm-3 dry bulk density.
      Root hairs were visualised within air-filled pore spaces, but not in the fine
      textured soil regions. We found that the genotype with root hairs significantly
      altered the porosity and connectivity of the detectable pore space (> 5 MUm) in
      the rhizosphere, as compared with the no-hair mutants. Both genotypes showed
      decreasing pore space between 0.8 and 0.1 mm from the root surface. Interestingly
      the root-hair-bearing genotype had a significantly greater soil pore volume
      fraction at the root-soil interface. Effects of pore structure on diffusion and
      permeability were estimated to be functionally insignificant under saturated
      conditions when simulated using image-based modelling.

PMID- 28758683
TI  - Effects of donor and acceptor's fluorescence lifetimes on the method of applying
      Forster resonance energy transfer in STED microscopy.
AB  - Forster resonance energy transfer (FRET) probes being used to improve the
      resolution of stimulated emission depletion (STED) microscopy are numerically
      discussed. Besides the FRET efficiency and the excitation intensity, the
      fluorescence lifetimes of donor and acceptor are found to be another key
      parameter for the resolution enhancement. Using samples of FRET pairs with
      shorter donor lifetime and longer acceptor lifetime enhances the nonlinearity of
      the donor fluorescence, which leads to an increased resolution. The numerical
      simulation shows that a double resolution improvement of STED microscopy can be
      achieved by using Cy3-Atto647N samples when compared with that of using standard
      Cy3-only samples.

PMID- 28758684
TI  - Delivery of cytoplasmic and apoplastic effectors from Phytophthora infestans
      haustoria by distinct secretion pathways.
AB  - The potato blight pathogen Phytophthora infestans secretes effector proteins that
      are delivered inside (cytoplasmic) or can act outside (apoplastic) plant cells to
      neutralize host immunity. Little is known about how and where effectors are
      secreted during infection, yet such knowledge is essential to understand and
      combat crop disease. We used transient Agrobacterium tumefaciens-mediated in
      planta expression, transformation of P. infestans with fluorescent protein
      fusions and confocal microscopy to investigate delivery of effectors to plant
      cells during infection. The cytoplasmic effector Pi04314, expressed as a
      monomeric red fluorescent protein (mRFP) fusion protein with a signal peptide to
      secrete it from plant cells, did not passively re-enter the cells upon secretion.
      However, Pi04314-mRFP expressed in P. infestans was translocated from haustoria,
      which form intimate interactions with plant cells, to accumulate at its sites of
      action in the host nucleus. The well-characterized apoplastic effector EPIC1, a
      cysteine protease inhibitor, was also secreted from haustoria. EPIC1 secretion
      was inhibited by brefeldin A (BFA), demonstrating that it is delivered by
      conventional Golgi-mediated secretion. By contrast, Pi04314 secretion was
      insensitive to BFA treatment, indicating that the cytoplasmic effector follows an
      alternative route for delivery into plant cells. Phytophthora infestans haustoria
      are thus sites for delivery of both apoplastic and cytoplasmic effectors during
      infection, following distinct secretion pathways.

PMID- 28758685
TI  - Derivatisation for separation and detection in capillary electrophoresis (2015
      2017).
AB  - Derivatisation is an integrated part of many analytical workflows to enable
      separation and detection of the analytes. In CE, derivatisation is adapted in the
      four modes of pre-capillary, in-line, in-capillary, and post-capillary
      derivatisation. In this review, we discuss the progress in derivatisation from
      February 2015 to May 2017 from multiple points of view including sections about
      the derivatisation modes, derivatisation to improve the analyte separation and
      analyte detection. The advancements in derivatisation procedures, novel reagents,
      and applications are covered. A table summarising the 46 reviewed articles with
      information about analyte, sample, derivatisation route, CE method and method
      sensitivity is provided.

PMID- 28758686
TI  - Do the Constructs of the FACES IV Change Based on Definitions of "Family?" A
      Measurement Invariance Test.
AB  - The Family Adaptability and Cohesion Scale (FACES) IV does not provide
      instructions about which family members respondents should think about while
      answering questions. This study examined which family members respondents thought
      about while completing the FACES IV, and if this changed measurement invariance
      and population heterogeneity of the measure. Using a sample of n = 511
      individuals, a latent class analysis showed three distinct classes: Nuclear
      Family, Family of Origin, and All of the Above. The FACES IV demonstrated
      measurement invariance across classes on the majority of subscales; however,
      population heterogeneity tests suggested that the means and variances of the
      subscales varied across classes. The findings suggest further examination of how
      the measure functions with unique family constellations is warranted.

PMID- 28758687
TI  - Root hairs enable high transpiration rates in drying soils.
AB  - Do root hairs help roots take up water from the soil? Despite the well-documented
      role of root hairs in phosphate uptake, their role in water extraction is
      controversial. We grew barley (Hordeum vulgare cv Pallas) and its root-hairless
      mutant brb in a root pressure chamber, whereby the transpiration rate could be
      varied whilst monitoring the suction in the xylem. The method provides accurate
      measurements of the dynamic relationship between the transpiration rate and xylem
      suction. The relationship between the transpiration rate and xylem suction was
      linear in wet soils and did not differ between genotypes. When the soil dried,
      the xylem suction increased rapidly and non-linearly at high transpiration rates.
      This response was much greater with the brb mutant, implying a reduced capacity
      to take up water. We conclude that root hairs facilitate the uptake of water by
      substantially reducing the drop in matric potential at the interface between root
      and soil in rapidly transpiring plants. The experiments also reinforce earlier
      observations that there is a marked hysteresis in the suction in the xylem when
      the transpiration rate is rising compared with when it is falling, and possible
      reasons for this behavior are discussed.

PMID- 28758689
TI  - The antiphasic regulatory module comprising CDF5 and its antisense RNA FLORE
      links the circadian clock to photoperiodic flowering.
AB  - Circadian rhythms of gene expression are generated by the combinatorial action of
      transcriptional and translational feedback loops as well as chromatin remodelling
      events. Recently, long noncoding RNAs (lncRNAs) that are natural antisense
      transcripts (NATs) to transcripts encoding central oscillator components were
      proposed as modulators of core clock function in mammals (Per) and fungi
      (frq/qrf). Although oscillating lncRNAs exist in plants, their functional
      characterization is at an initial stage. By screening an Arabidopsis thaliana
      lncRNA custom-made array we identified CDF5 LONG NONCODING RNA (FLORE), a
      circadian-regulated lncRNA that is a NAT of CDF5. Quantitative real-time RT-PCR
      confirmed the circadian regulation of FLORE, whereas GUS-staining and flowering
      time evaluation were used to determine its biological function. FLORE and CDF5
      antiphasic expression reflects mutual inhibition in a similar way to frq/qrf.
      Moreover, whereas the CDF5 protein delays flowering by directly repressing FT
      transcription, FLORE promotes it by repressing several CDFs (CDF1, CDF3, CDF5)
      and increasing FT transcript levels, indicating both cis and trans function. We
      propose that the CDF5/FLORE NAT pair constitutes an additional circadian
      regulatory module with conserved (mutual inhibition) and unique (function in
      trans) features, able to fine-tune its own circadian oscillation, and
      consequently, adjust the onset of flowering to favourable environmental
      conditions.

PMID- 28758691
TI  - Diverse belowground resource strategies underlie plant species coexistence and
      spatial distribution in three grasslands along a precipitation gradient.
AB  - Functional traits and their variation mediate plant species coexistence and
      spatial distribution. Yet, how patterns of variation in belowground traits
      influence resource acquisition across species and plant communities remains
      obscure. To characterize diverse belowground strategies in relation to species
      coexistence and abundance, we assessed four key belowground traits - root
      diameter, root branching intensity, first-order root length and mycorrhizal
      colonization - in 27 coexisting species from three grassland communities along a
      precipitation gradient. Species with thinner roots had higher root branching
      intensity, but shorter first-order root length and consistently low mycorrhizal
      colonization, whereas species with thicker roots enhanced their capacity for
      resource acquisition by producing longer first-order roots and maintaining high
      mycorrhizal colonization. Plant species observed across multiple sites
      consistently decreased root branching and/or mycorrhizal colonization, but
      increased lateral root length with decreasing precipitation. Additionally, the
      degree of intraspecific trait variation was positively correlated with species
      abundance across the gradient, indicating that high intraspecific trait variation
      belowground may facilitate greater fitness and chances of survival across
      multiple habitats. These results suggest that a small set of critical belowground
      traits can effectively define diverse resource acquisition strategies in
      different environments and may forecast species survival and range shifts under
      climate change.

PMID- 28758690
TI  - Rearing-environment-dependent hippocampal local field potential differences in
      wild-type and inositol trisphosphate receptor type 2 knockout mice.
AB  - KEY POINTS: Mice reared in an enriched environment are demonstrated to have
      larger hippocampal gamma oscillations than those reared in isolation, thereby
      confirming previous observations in rats. To test whether astrocytic Ca2+ surges
      are involved in this experience-dependent LFP pattern modulation, we used
      inositol trisphosphate receptor type 2 (IP3 R2)-knockout (KO) mice, in which IP3
      /Ca2+ signalling in astrocytes is largely diminished. We found that this
      experience-dependent gamma power alteration persists in the KO mice.
      Interestingly, hippocampal ripple events, the synchronized events critical for
      memory consolidation, are reduced in magnitude and frequency by both isolated
      rearing and IP3 R2 deficiency. ABSTRACT: Rearing in an enriched environment (ENR)
      is known to enhance cognitive and memory abilities in rodents, whereas social
      isolation (ISO) induces depression-like behaviour. The hippocampus has been
      documented to undergo morphological and functional changes depending on these
      rearing environments. For example, rearing condition during juvenility alters CA1
      stratum radiatum gamma oscillation power in rats. In the present study,
      hippocampal CA1 local field potentials (LFP) were recorded from bilateral CA1 in
      urethane-anaesthetized mice that were reared in either an ENR or ISO condition.
      Similar to previous findings in rats, gamma oscillation power during theta states
      was higher in the ENR group. Ripple events that occur during non-theta periods in
      the CA1 stratum pyramidale also had longer intervals in ISO mice. Because
      astrocytic Ca2+ elevations play a key role in synaptic plasticity, we next tested
      whether these changes in LFP are also expressed in inositol trisphosphate
      receptor type 2 (IP3 R2)-knockout (KO) mice, in which astrocytic Ca2+ elevations
      are largely diminished. We found that the gamma power was also higher in IP3 R2
      KO-ENR mice compared to IP3 R2-KO-ISO mice, suggesting that the rearing
      environment-dependent gamma power alteration does not necessarily require the
      astrocytic IP3 /Ca2+ pathway. By contrast, ripple events showed genotype
      dependent changes, as well as rearing condition-dependent changes: ISO housing
      and IP3 R2 deficiency both lead to longer inter-ripple intervals. Moreover, we
      found that ripple magnitude in the right CA1 tended to be smaller in IP3 R2-KO.
      Because IP3 R2-KO mice have been reported to have depression phenotypes, our
      results suggest that ripple events and the mood of animals may be broadly
      correlated.

PMID- 28758692
TI  - The impact of a universal intervention targeting perfectionism in children: An
      exploratory controlled trial.
AB  - OBJECTIVES: Perfectionism is considered to be an underlying mechanism of
      relevance to a broad array of indicators of psychological distress. The current
      research examined the impact of a three-session intervention targeting
      perfectionism in children on perfectionism, self-criticism, and well-being.
      DESIGN: The design of the current study can be considered quasi-experimental as
      the intervention and control classes were not randomly allocated but decided by
      convenience factors at the school level. METHODS: Students (aged 10.08-12.79
      years) were allocated to the intervention (N = 107, 41 boys) or control condition
      (N = 105, 33 boys), completing self-report assessments on perfectionism, self
      criticism, and well-being at baseline, post-intervention, and 3-month follow-up.
      RESULTS: At post-intervention, children in the intervention group had
      significantly lower perfectionism than the control group (d = 0.35, 95%
      confidence intervals [CI]: 0.07-0.62) and at 3-month follow-up had significantly
      higher levels of well-being (d = 0.33, 95% CI: 0.06-0.60). As predicted by
      theory, decreases in perfectionism mediated the relationship between condition
      and improved well-being. CONCLUSIONS: This exploratory study provides evidence
      for the usefulness of a brief universal prevention programme targeting
      perfectionism. Future research should use more robust designs, explore longer
      term effects, and the impact on a wider range of variables, including scholastic
      achievement. PRACTITIONER POINTS: Clinical implications Perfectionism linked with
      negative outcomes in children can be decreased in a classroom setting. Decreasing
      perfectionism leads to improved well-being in children. Limitations More rigorous
      designs along with better assessment of perfectionism are required in further
      evaluations. The impact of perfectionism on scholastic achievement in children
      requires further investigation.

PMID- 28758693
TI  - Amino-Mediated Anchoring Perovskite Quantum Dots for Stable and Low-Threshold
      Random Lasing.
AB  - Halide perovskite quantum dots (Pe-QDs) have been considered as outstanding
      candidates for photodetector, light-emitting diode, and lasing applications, but
      these perspectives are being impeded by the severe stability, including both
      chemical and optical degradations. This study reports on amino-mediated anchoring
      Pe-QDs onto the surfaces of monodisperse silica to effectively depress the
      optical degradation of their photoluminescence (PL) and random lasing
      stabilities, hence achieving highly stable and low-threshold lasing. An amination
      mediated nucleation and growth process is designed for the general and one-pot
      synthesis of Pe-QDs on the surfaces of silica spheres. The facile synthetic
      process, which can be finished within several minutes, insures scalable
      production. Surprisingly, almost no PL degradation is observed after 40 d storage
      under ambient conditions, even 80% PL intensity can be maintained after
      persistently illuminated by UV lamps for 108 h. Subsequently, extremely stable
      random lasing is achieved after storage for 2 months or over continuously optical
      pumping for 8 h. Such high PL and lasing stabilities originate from the isolation
      effects due to the effective anchoring, which separate the Pe-QDs from each other
      and inhibit the photoinduced regrowth and deterioration. This work will also open
      the window of perovskite-based multifunctional systems.

PMID- 28758694
TI  - Comparison of caffeine disposition following administration by oral solution
      (energy drink) and inspired powder (AeroShot) in human subjects.
AB  - AIMS: To determine the disposition and effects of caffeine after administration
      using a new dosage form (AeroShot) that delivers caffeine by inspiration of a
      fine powder into the oral cavity and compare it to an equivalent dose of an oral
      solution (energy drink) as the reference standard. METHODS: Healthy human
      subjects (n = 17) inspired a 100 mg caffeine dose using the AeroShot device or
      consumed an energy drink on separate study days. Heart rate, blood pressure and
      subject assessments of effects were measured over an 8-h period. Plasma
      concentrations of caffeine and its major metabolites were determined by liquid
      chromatography-mass spectrometry. Pharmacokinetic, cardiovascular and perceived
      stimulant effects were compared between AeroShot and energy drink phases using a
      paired t test and standard bioequivalency analysis. RESULTS: Caffeine disposition
      was similar after caffeine administration by the AeroShot device and energy
      drink: peak plasma concentration 1790 and 1939 ng ml-1 , and area under the
      concentration-time curve (AUC) 15 579 and 17 569 ng ml-1 * h, respectively, but
      they were not bioequivalent: AeroShot AUC of 80.3% (confidence interval 71.2
      104.7%) and peak plasma concentration of 86.3% (confidence interval 62.8-102.8%)
      compared to the energy drink. Female subjects did have a significantly larger AUC
      compared to males after consumption of the energy drink. The heart rate and blood
      pressure were not significantly affected by the 100 mg caffeine dose, and there
      were no consistently perceived stimulant effects by the subjects using visual
      analogue scales. CONCLUSION: Inspiration of caffeine as a fine powder using the
      AeroShot device produces a similar caffeine profile and effects compared to
      administration of an oral solution (energy drink).

PMID- 28758695
TI  - Sperm membrane integrity and stability after selection of cryopreserved ovine
      semen on colloidal solutions.
AB  - The aim of this study was to evaluate the effect of four methods of sperm
      selection, on the integrity and stability of the plasma membrane, integrity of
      the acrosomal membrane and spermatic morphology in frozen/thawed ovine semen. Two
      types of colloidal silica: colloidal silica-silane and colloidal silica
      polyvinylpyrrolidone (PVP), and two aliquots: 1 and 4 ml, were used for sperm
      selection. Probes FITC-PSA and PI were used to measure the integrity of the
      plasma and acrosomal membranes. Plasma membrane stability was measured, using
      fluorescent probes M540 and YOPRO1. Effective reduction in the incidence of
      spermatozoa with acrosomal pathologies was only achieved using 1 ml colloidal
      silica-silane. All methods were efficient in select viable and unreacted
      spermatozoa. Only methods using 1 ml of silica were efficient in decrease
      spermatozoa stained by PI (death). Methods using silica colloidal-silane were
      more efficient to decrease apoptotic cells after selection when compared to
      silica colloidal-PVP. In conclusion, sperm selection in colloidal silica-silane
      and colloidal silica-PVP improved sperm quality when compared to the controls.
      The method using 1 ml of colloidal silica-silane is the preferred method because
      its effectiveness and lower cost.

PMID- 28758696
TI  - 53% Efficient Red Emissive Carbon Quantum Dots for High Color Rendering and
      Stable Warm White-Light-Emitting Diodes.
AB  - Red emissive carbon quantum dots (R-CQDs) with quantum yield of 53% is
      successfully prepared. An ultraviolet (UV)-pumped CQD phosphors-based warm white
      light-emitting diode (WLED) is realized for the first time and achieves a color
      rendering index of 97. This work provides a new avenue for the exploration of low
      cost, environment-friendly, and high-performance CQD phosphors-based warm WLEDs.

PMID- 28758698
TI  - Patients with established cancer cachexia lack the motivation and self-efficacy
      to undertake regular structured exercise.
AB  - OBJECTIVES: Patients with advanced cancer frequently suffer a decline in
      activities associated with involuntary loss of weight and muscle mass (cachexia).
      This can profoundly affect function and quality of life. Although exercise
      participation can maintain physical and psychological function in patients with
      cancer, uptake is low in cachectic patients who are underrepresented in exercise
      studies. To understand how such patients' experiences are associated with
      exercise participation, we investigated exercise history, self-confidence, and
      exercise motivations in patients with established cancer cachexia, and
      relationships between relevant variables. METHODS: Lung and gastrointestinal
      cancer outpatients with established cancer cachexia (n = 196) completed a
      questionnaire exploring exercise history and key constructs of the Theory of
      Planned Behaviour relating to perceived control, psychological adjustment, and
      motivational attitudes. RESULTS: Patients reported low physical activity levels,
      and few undertook regular structured exercise. Exercise self-efficacy was very
      low with concerns it could worsen symptoms and cause harm. Patients showed poor
      perceived control and a strong need for approval but received little advice from
      health care professionals. Preferences were for low intensity activities, on
      their own, in the home setting. Regression analysis revealed no significant
      factors related to the independent variables. CONCLUSIONS: Frequently employed
      higher intensity, group exercise models do not address the motivational and
      behavioural concerns of cachectic cancer patients in this study. Developing
      exercise interventions which match perceived abilities and skills is required to
      address challenges of self-efficacy and perceived control identified. Greater
      engagement of health professionals with this group is required to explore
      potential benefits of exercise.

PMID- 28758699
TI  - Chronic hypobaric hypoxia diminishes the expression of base excision repair OGG1
      enzymes in spermatozoa.
AB  - Hypobaric hypoxia induces DNA damage in rat testicular cells, the production of
      defective spermatozoids and decreased sperm count, associated with an increase in
      oxidative stress. 8-Oxoguanine glycosylase (OGG1) enzymes are main members of the
      base excision repair (BER) system, a DNA repair mechanism. We determined the
      expression levels of mitochondrial and nuclear OGG1 isoforms in spermatozoa
      collected from cauda epididymis in rats exposed to chronic hypobaric hypoxia
      (CHH) for 5, 15 and 30 days. CHH attenuates OGG1 expression in a time-dependent
      fashion, with a greater reduction in the mitochondrial isoform OGG1-2a (p < .05).
      Attenuation of the BER system may contribute to DNA damage under hypoxia
      exposure.

PMID- 28758700
TI  - Dengue virus infections among blood donors in Guangxi of China, 2013-2014.
AB  - BACKGROUND: An unexpected, large dengue outbreak, spreading to 20 cities of
      Guangdong province, occurred in July 2014. Considering the overwhelming influence
      of this seasonal epidemic, whether this dengue virus outbreak has an significant
      impact on the blood donors of the ajacent areas in Guangdong requires at least a
      preliminary investigation. Liuzhou City of Guangxi was chosen as a good
      representative of the neighbouring geographical location of the dengue virus
      (DENV) outbreak areas in this research. We therefore investigated qualified blood
      donations during potential dengue epidemic seasons and thus provided critical
      information for public health and donation policy making. METHOD: A total of 1685
      donations from 2013 to 2014 were collected at the Guangxi blood centre. Anti-DENV
      testing was performed using enzyme-linked immunosorbent assay (ELISA). Dengue IgG
      indirect ELISA and Dengue IgM capture ELISA were used to detect anti-DENV IgM and
      IgG. Repeat-reactive samples with ELISA test and 1685 donations with 421 pools
      were screened for dengue RNA by reverse transcription real-time quantitative
      polymerase chain reaction (RT-qPCR) using an in-house assay. RESULTS: There was a
      total of 13 seropositive donors, including 6 IgM seropositive and 7 IgG
      seropositive. The total seropositive rate was 0.78%, with IgM 0.36% and IgG
      0.42%. Seropositive donors were identified mostly between April and November,
      with a peak in November. .All samples in reactive pools and individual
      seropositive samples were negative in the follow-up RT-PCR test. CONCLUSION: Our
      results suggested that the Guangdong dengue outbreak had limited impact on blood
      safety in surrounding areas under our current testing system.

PMID- 28758697
TI  - Renal toxicity and chemotherapy in children with cancer.
AB  - The clinical use of antineoplastic drugs can be limited by different drug-induced
      toxicities. Of these, renal dysfunction may be one of the most troublesome in
      that it can be cumulative and in general is only partially reversible with the
      discontinuation of the treatment. Renal toxicity may be manifested as a reduction
      of the glomerular filtration rate, electrolyte imbalances, or acute renal
      failure. Careful assessment of renal function has to be performed taking into
      account that the impairment of renal function is initially silent and only later
      may be clinically dramatic. When clinically indicated, the reduction or, in cases
      of severe nephrotoxicity, the suspension of chemotherapy should be considered to
      avoid the progressive deterioration of the compromised glomerular and/or tubular
      function.

PMID- 28758701
TI  - Effectiveness of self-management programmes in diabetes management: A systematic
      review.
AB  - BACKGROUND: Diabetes is a major noncommunicable disease, which is increasing, and
      approximately 415 million people are affected around the globe. Since diabetes is
      a lifelong disease, patients require better understanding and knowledge of the
      condition to become self-reliant in making diabetes-related decisions. AIMS: This
      systematic review was performed to assess the effectiveness of diabetes self
      management programs in people with type 2 diabetes. METHODS: A comprehensive
      literature search was undertaken to identify all published English language
      articles through EBSCO discovery services in the following electronic database:
      Science Direct, CINAHL Plus with Full Text, MEDLINE, and Access Medicine. Studies
      were published from January 2000 to October 2015. The initial search retrieved 37
      566 studies and based on the inclusion criteria, 14 studies were selected for
      review. RESULTS: Of 14 studies, most findings favoured diabetes self-management.
      But the overall effectiveness of individual interventions was not conclusive. A
      wide variety of interventions was used including diabetes education as a major
      component in self-management programs. CONCLUSION: Interventions used varied
      strategies in differing composition, and further work is needed to find out the
      effectiveness of individual interventions.

PMID- 28758702
TI  - A Direct Arylation-Cyclisation Reaction for the Construction of Medium-Sized
      Rings.
AB  - A strategy for assembling biaryls linked through a medium-sized ring is herein
      presented. pi-Complexation of fluoroarenes to chromium tricarbonyl activates the
      molecule towards both C-H activation and nucleophilic aromatic substitution
      without covalently altering the molecular connectivity of the arene. The
      construction of bridged biaryl molecules with 6-10-membered core rings is
      achieved through a one-pot C-H arylation/nucleophilic aromatic substitution
      sequence. The methodology is applicable to the synthesis of heterocyclic as well
      as fully carbocyclic rings.

PMID- 28758703
TI  - Copper-Catalyzed Enantioselective Domino Arylation/Semipinacol Rearrangement of
      Allylic Alcohols with Diaryliodonium Salts.
AB  - A copper-catalyzed enantioselective arylative semipinacol rearrangement of
      allylic alcohols was developed. In the presence of a catalytic amount of an in
      situ generated chiral copper-bisoxazoline complex, reaction of allylic alcohols
      with diaryliodonium salts afforded spirocycloalkanones in high yields with high
      diastereo- and enantioselectivities. A two-point binding model engaging the
      carbon-carbon double bond and the proximal hydroxyl group was proposed to be
      responsible for the highly efficient chirality transfer.

PMID- 28758704
TI  - An Ecological Investigation of the Emotional Context Surrounding Nonsuicidal Self
      Injurious Thoughts and Behaviors in Adolescents and Young Adults.
AB  - Ecological momentary assessment (EMA) methodology was used to examine the
      emotional context of nonsuicidal self-injury (NSSI). Forty-seven adolescents and
      young adults used a novel smartphone app to monitor their emotional experiences,
      NSSI thoughts, and NSSI behaviors for 2 weeks. Momentary changes in both negative
      and positive emotions predicted greater intensity of NSSI thoughts at the
      subsequent assessment, while only increases in negative emotion predicted NSSI
      behaviors. Immediately following NSSI behaviors participants reported reduced
      high-arousal negative emotions and increased low-arousal positive emotions,
      suggesting that NSSI may be an efficient and effective method of regulating
      emotion. Findings highlight the importance of addressing emotion regulation in
      NSSI interventions.

PMID- 28758705
TI  - Coping with changes and uncertainty: A qualitative study of young adult cancer
      patients' challenges and coping strategies during treatment.
AB  - Young adult cancer patients (YACPs), aged 18-35 years when diagnosed with cancer,
      are in a vulnerable transitioning period from adolescence to adulthood, where
      cancer adds a tremendous burden. However, YACPs' challenges and coping strategies
      are under-researched. The objective of this study was to explore what challenges
      YACP experience during their treatment, and what coping strategies they applied
      to them. We conducted a qualitative study with a phenomenological-hermeneutic
      design, including retrospective, semi-structured interviews of 16 YACPs who had
      undergone cancer treatment. Data were analysed using thematic analysis and
      interpreted applying the Cognitive Activation Theory of Stress (CATS). We found
      "coping with changes and uncertainty" as overarching topic for YACPs' challenges,
      particularly related to five themes, including (1) receiving the diagnosis, (2)
      encountering the healthcare system, (3) living with cancer, (4) dealing with the
      impact of the treatment and (5) reactions from the social network. YACPs' coping
      strategies applied to these challenges varied broadly and ranged from maladaptive
      strategies, such as neglecting the situation, to conducive emotional or
      instrumental approaches to manage their challenges. The findings call for age
      specific needs assessments, information and support for YACPs, and their families
      in order to facilitate YACPs' coping during their treatment.

PMID- 28758706
TI  - Transition Metal Catalyzed, Regioselective B(4)-Halogenation and B(4,5)
      Diiodination of Cage B-H Bonds in o-Carboranes.
AB  - Transition metal catalyzed, regioselective carborane-cage B(4)-H iodination,
      bromination, and chlorination as well as B(4,5)-H diiodination were achieved by
      using NXS (X=I, Br), FeCl3 , or IOAc as the halogenating agent, respectively. A
      series of previously inaccessible B(4)-halogenated o-carboranes were synthesized
      in a simple one-pot process, and proved to be valuable synthons for the
      functionalization of carboranes. Mono- and di-selectivity can be controlled by in
      situ removal of the carboxy directing group. The resultant 4-I-o-C2 B10 H11 can
      serve as a versatile feedstock for the construction of cage B-C(sp2 ), B-C(sp), B
      O, and B-N bonds.

PMID- 28758707
TI  - Polymer-Stabilized Micropixelated Liquid Crystals with Tunable Optical Properties
      Fabricated by Double Templating.
AB  - Self-organized nano- and microstructures of soft materials are attracting
      considerable attention because most of them are stimuli-responsive due to their
      soft nature. In this regard, topological defects in liquid crystals (LCs) are
      promising not only for self-assembling colloids and molecules but also for
      electro-optical applications such as optical vortex generation. However, there
      are currently few bottom-up methods for patterning a large number of defects
      periodically over a large area. It would be highly desirable to develop more
      effective techniques for high-throughput and low-cost fabrication. Here, a
      micropixelated LC structure consisting of a square array of topological defects
      is stabilized by photopolymerization. A polymer network is formed on the
      structure of a self-organized template of a nematic liquid crystal (NLC), and
      this in turn imprints other nonpolymerizable NLC molecules, which maintains their
      responses to electric field and temperature. Photocuring of specific local
      regions is used to create a designable template for the reproducible self
      organization of defects. Moreover, a highly diluted polymer network (~0.1 wt%
      monomer) exhibits instant on-off switching of the patterns. Beyond the mere
      stabilization of patterns, these results demonstrate that the incorporation of
      self-organized NLC patterns offers some unique and unconventional applications
      for anisotropic polymer networks.

PMID- 28758708
TI  - Electrospun magnetic polybutylene terephthalate nanofibers for thin film
      microextraction.
AB  - A thin film microextraction method using elecrospun magnetic polybutylene
      terephthalate nanofibers is developed and implemented to isolate some selected
      triazines. Due to the high mechanical stability of these nanofibers, they are
      repeatedly used under harsh magnetic stirring and ultrasonic conditions without
      any damage and structure degradation. The presence of magnetic nanoparticles
      within the nanofiber structure increases the extraction efficiency while the
      fibers could be collected by an external magnet. The synthesized nanocomposite
      showed strong affinity toward the selected analytes. Apart from the concentration
      of magnetic nanoparticles within the nanocomposite network, the effect of
      different parameters on the extraction and desorption processes including the
      sample pH, extraction time, sample volume, type of desorption solvent, solvent
      volume, and desorption time were optimized. Eventually, the detection limits were
      in the range of 0.02-0.05 ng/mL, while the limits of quantification were between
      0.1 and 0.2 ng/mL. The linear dynamic range was 0.1-100 ng/mL, and the relative
      standard deviations were 4-9% (n = 3). The developed method was extended to the
      real water samples, and the relative recoveries were in the range of 86-103%,
      indicating that the prepared sorbent is suitable for extraction of triazines from
      environmental samples.

PMID- 28758709
TI  - American Indian and Alaska Native Men's Use of Sexual Health Services, 2006-2010.
AB  - CONTEXT: American Indian and Alaska Native men experience poorer sexual health
      than white men. Barriers related to their sex and racial identity may prevent
      them from seeking care; however, little is known about this population's use of
      sexual health services. METHODS: Sexual health service usage was examined among
      923 American Indian and Alaska Native men and 5,322 white men aged 15-44 who
      participated in the 2006-2010 National Survey of Family Growth. Logistic
      regression models explored differences in service use by race and examined
      correlates of use among American Indians and Alaska Natives. RESULTS: Among men
      aged 15-19 and those aged 35-44, men with incomes greater than 133% of the
      federal poverty level, men with private insurance, those living in the Northeast
      and those living in rural areas, American Indians and Alaska Natives were more
      likely than whites to use STD or HIV services (odds ratios, 1.5-3.2). The odds of
      birth control service use did not differ by race. Differences in service use were
      found among American Indian and Alaska Native men: For example, those with a
      usual source of care had elevated odds of using sexual health services (1.9-3.4),
      while those reporting no recent testicular exam had reduced odds of using these
      services (0.3-0.4). CONCLUSIONS: This study provides baseline data on American
      Indian and Alaska Native men's use of sexual health services. Research exploring
      these men's views on these services is needed to help develop programs that
      better serve them.

PMID- 28758710
TI  - Multimodality assessment of left ventricular dysfunction in Takayasu arteritis
      and familial hypercholesterolaemia.
AB  - Although left ventricular (LV) systolic dysfunction in patients suffering from
      Takayasu arteritis (TA) has been reported, little is known regarding the
      development of heart failure in these patients. We report a novel finding of
      active TA and familial hypercholesterolaemia presenting with severe LV
      dysfunction through multimodality assessments of LV systolic dysfunction.

PMID- 28758711
TI  - Enantioseparation of pheniramine enantiomers by high-speed countercurrent
      chromatography using beta-cyclodextrin derivatives as a chiral selector.
AB  - The enantioselective separation of pheniramine was studied by a high-speed
      countercurrent chromatography method using beta-cyclodextrin derivatives as a
      chiral selector. Several key variables, for instance, type of organic solvent and
      chiral selector, concentration of chiral selector, pH value of aqueous phase, and
      temperature on the enantioselectivity, were investigated systematically by liquid
      liquid extraction experiments. Combining the results of extraction experiments
      and high-speed countercurrent chromatography, the most suitable conditions for
      separation of pheniramine enantiomers were obtained with the two-phase system
      that consisted of isobutyl acetate/aqueous phase, containing 0.02 mol/L
      carboxymethyl-beta-cyclodextrin, pH 8.50 at 278.15 K. Under the optimal
      conditions, pheniramine enantiomer was successfully resolved after four cycles of
      high-speed countercurrent chromatography. By using high-performance liquid
      chromatography to analyze the fractions, the purities of both (+)-pheniramine and
      (-)-pheniramine were over 99% and the recovery of this method was up to 85-90%.

PMID- 28758713
TI  - In Situ Assembly of Au Nanoclusters within Protein Hydrogel Networks.
AB  - We report a new approach of in situ assembling gold nanoclusters (AuNCs) into
      hydrogel networks by exploiting the triple roles of protein as a gelator, a
      reducing agent as well as a template. The strategy simply involves the mixing of
      BSA and AuCl4- under alkaline condition. The obtained AuNCs-protein nanocomposite
      hydrogels with injectable and moldable features can be made into semi-transparent
      films or N-doped C/Au composites. Our work demonstrates the feasibility of
      fabricating AuNCs in situ embedded in hybrid hydrogels, which can serve as
      multifunctional precursors for constructing diverse nanocomposite materials.

PMID- 28758712
TI  - Spatiotemporally Controlled Release of Rho-Inhibiting C3 Toxin from a Protein-DNA
      Hybrid Hydrogel for Targeted Inhibition of Osteoclast Formation and Activity.
AB  - In osteoporosis, bone structure can be improved by the introduction of
      therapeutic molecules inhibiting bone resorption by osteoclasts. Here,
      biocompatible hydrogels represent an excellent option for the delivery of
      pharmacologically active molecules to the bone tissue because of their
      biodegradability, injectability, and manifold functionalization capacity. The
      present study reports the preparation of a multifunctional hybrid hydrogel from
      chemically modified human serum albumin and rationally designed DNA building
      blocks. The hybrid hydrogel combines advantageous characteristics, including
      rapid gelation through DNA hybridization under physiological conditions and a
      self-healing and injectable nature with the possibility of specific loading and
      spatiotemporally controlled release of active proteins, making it an advanced
      biomaterial for the local treatment of bone diseases, for example, osteoporosis.
      The hydrogels are loaded with a recombinant Rho-inhibiting C3 toxin, C2IN-C3lim
      G205C. This toxin selectively targets osteoclasts and inhibits Rho-signaling and,
      thereby, actin-dependent processes in these cells. Application of C2IN-C3lim
      G205C toxin-loaded hydrogels effectively reduces osteoclast formation and
      resorption activity in vitro, as demonstrated by tartrate-resistant acid
      phosphatase staining and the pit resorption assay. Simultaneously, osteoblast
      activity, viability, and proliferation are unaffected, thus making C2IN-C3lim
      G205C toxin-loaded hybrid hydrogels an attractive pharmacological system for
      spatial and selective modulation of osteoclast functions to reduce bone
      resorption.

PMID- 28758714
TI  - Tiered Electron Anions in Multiple Voids of LaScSi and Their Applications to
      Ammonia Synthesis.
AB  - Electrides-compounds in which electrons localized in interstitial spaces
      periodically serve as anions-have attracted broad attention for their exotic
      properties, such as extraordinary electron-donating ability. In our efforts to
      expand this small family of phases, LaScSi emerges as a promising candidate. Its
      electron count is 2e- f.u.-1 in excess of that expected from the Zintl concept,
      while its structure offers interstitial spaces that can accommodate these extra
      electrons. Herein, this potential is explored through density functional theory
      (DFT) calculations and property measurements on LaScSi. DFT calculations
      (validated by heat capacity and electrical transport measurements) reveal
      electron density peaks at two symmetry-distinct interstitial sites. Importantly,
      this electride-like character is combined with chemical stability in air and
      water, an advantage for catalysis. Ru-loaded LaScSi shows outstanding catalytic
      activity for ammonia synthesis, with a turnover frequency (0.1 s-1 at 0.1 MPa,
      400  degrees C) an order of magnitude higher than those of oxide-based Ru
      catalysts, e.g., Ru/MgO. As with other electrides, LaScSi's ability to reversibly
      store hydrogen prevents the hydrogen poisoning of Ru surfaces. The better
      performance of LaScSi, however, hints at the importance of the high concentration
      (>1.6 * 1022 cm-3 ) and tiered nature of its anionic electrons, which offers
      guidance toward new catalysts.

PMID- 28758716
TI  - TiF4 gel effects on tubular occlusion of eroded/abraded human dentin.
AB  - This in situ study evaluated the tubular occlusion caused by 4% TiF4 gel on the
      surface of eroded/abraded dentin. Sixty human dentin samples were eroded in vitro
      and assigned into six groups (n = 10) according to the in situ surface treatment
      and number of cycling days: 4% TiF4 gel applied once (TiF4 1), twice (TiF4 2), or
      three times (TiF4 3) followed by 2, 4, and 6 days of erosive/abrasive in situ
      cycling, respectively. Control groups (no treatment) were subjected to 2 (C1), 4
      (C2), and 6 (C3) days of erosive/abrasive in situ cycling only. A seventh group
      (n = 10) was comprised by in vitro uneroded samples (UN), subjected to 6 days of
      in situ erosive/abrasive cycling. Each cycling day consisted on six erosive (0.5%
      citric acid, pH 2.6) and one abrasive events. Environmental scanning electron
      microscopy micrographs were taken. For all groups, blinded examiners assessed
      dentin tubules occlusion using visual scores (0-unoccluded, 1-partially occluded
      by granular deposits, 2-partially occluded by reduction in tubular lumen into
      diamond shape, 3-completely occluded) on images captured prior and after the in
      situ phase. Scheirer-Ray-Hare test demonstrated that treatments significantly
      affected tubule occlusion (p < .001). Dunn's test showed that tubule occlusion in
      TiF4 3 was significantly higher than in C1. Tubule occlusion in remaining groups
      did not differ from that observed in groups TiF4 3 and C1. Tubule occlusion was
      significantly higher after in situ phase. It may be suggested that TiF4 , when
      applied three times, was able to positively change tubule occlusion of dentin
      samples.

PMID- 28758715
TI  - Serial Sonographic Assessment of Pulmonary Edema in Patients With Hypertensive
      Acute Heart Failure.
AB  - OBJECTIVES: Objective measures of clinical improvement in patients with acute
      heart failure (AHF) are lacking. The aim of this study was to determine whether
      repeated lung sonography could semiquantitatively capture changes in pulmonary
      edema (B-lines) in patients with hypertensive AHF early in the course of
      treatment. METHODS: We conducted a feasibility study in a cohort of adults with
      acute onset of dyspnea, severe hypertension in the field or at triage (systolic
      blood pressure >= 180 mm Hg), and a presumptive diagnosis of AHF. Patients
      underwent repeated dyspnea and lung sonographic assessments using a 10-cm visual
      analog scale (VAS) and an 8-zone scanning protocol. Lung sonographic assessments
      were performed at the time of triage, initial VAS improvement, and disposition
      from the emergency department. Sonographic pulmonary edema was independently
      scored offline in a randomized and blinded fashion by using a scoring method that
      accounted for both the sum of discrete B-lines and degree of B-line fusion.
      RESULTS: Sonographic pulmonary edema scores decreased significantly from initial
      to final sonographic assessments (P < .001). The median percentage decrease among
      the 20 included patient encounters was 81% (interquartile range, 55%-91%).
      Although sonographic pulmonary edema scores correlated with VAS scores (rho =
      0.64; P < .001), the magnitude of the change in these scores did not correlate
      with each other (rho = -0.04; P = .89). CONCLUSIONS: Changes in sonographic
      pulmonary edema can be semiquantitatively measured by serial 8-zone lung
      sonography using a scoring method that accounts for B-line fusion. Sonographic
      pulmonary edema improves in patients with hypertensive AHF during the initial
      hours of treatment.

PMID- 28758717
TI  - EPA + DHA supplementation reduces PMN activation in microenvironment of chronic
      venous leg ulcers: A randomized, double-blind, controlled study.
AB  - Sustained high levels of activated polymorphonuclear leukocytes (PMNs) and PMN
      derived proteases in the microenvironment of chronic venous leg ulcers (CVLUs)
      are linked to chronic inflammation and delayed healing. Uncontrolled PMN activity
      eventually destroys newly developed tissue and degrades critical growth factors.
      The bioactive components of fish oil (n-3 eicosapentaenoic acid [EPA] and
      docosahexaenoic acid [DHA]) have strong inflammation-resolving actions and have
      been shown to assuage PMN activity, but have not been tested in CVLU patients.
      This randomized controlled study compared the effectiveness of oral EPA + DHA
      therapy to a placebo for reducing PMN activation in CVLU microenvironments. At
      Days 0, 28, and 56, markers of PMNs (CD15) and activated PMNs (CD66b), and levels
      of PMN-derived proteases human neutrophil elastase and matrix metalloproteinase-8
      were measured in CVLU fluid from patients receiving standard compression therapy
      and (1) EPA + DHA therapy (n = 16) or (2) placebo (n = 19). By Day 56, the EPA +
      DHA Group had a significantly lower percentage of CD66b+ cells in CVLU fluid
      compared to Day 0 (p = 0.02) and to Day 28 (p = 0.05). Importantly, there were
      downward trends in levels of both matrix metalloproteinase-8 and human neutrophil
      elastase over time in the EPA + DHA Group, which also demonstrated greater
      reductions in wound area by Day 28 (57% reduction) and Day 56 (76% reduction)
      than the Control Group (35% and 59%, respectively). Moreover, reductions in wound
      area had significant negative relationships with CD15+ cells in wound fluid at
      Days 28 (p = 0.008) and 56 (p < 0.001), and CD66b+ cells at Days 28 (p = 0.04)
      and 56 (p = 0.009). The collective findings provide supplemental evidence that
      high levels of activated PMNs in CVLU microenvironments inhibit healing, and
      suggest that EPA + DHA oral therapy may modulate PMN activity and facilitate
      healing of CVLUs when added to standard care regimens.

PMID- 28758718
TI  - Tritopic NHC Precursors: Unusual Nickel Reactivity and Ethylene Insertion into a
      C(sp3 )-H Bond.
AB  - The imidazolium chloride [C3 H3 N(C3 H6 NMe2 )N{C(Me)(=NDipp)}]Cl (1; Dipp=2,6
      diisopropyl phenyl), a potential precursor to a tritopic Nimine CNHC Namine
      pincer-type ligand, reacted with [Ni(cod)2 ] to give the NiI -NiI complex 2,
      which contains a rare cod-derived eta3 -allyl-type bridging ligand. The implied
      intermediate formation of a nickel hydride through oxidative addition of the
      imidazolium C-H bond did not occur with the symmetrical imidazolium chloride [C3
      H3 N2 {C(Me)(=NDipp)}2 ]Cl (3). Instead, a Ni-C(sp3 ) bond was formed, leading to
      the neutral Nimine CHNimine pincer-type complex Ni[C3 H3 N2 {C(Me)(=NDipp)}2 ]Cl
      (4). Theoretical studies showed that this highly unusual feature in nickel NHC
      chemistry is due to steric constraints induced by the N substituents, which
      prevent Ni-H bond formation. Remarkably, ethylene inserted into the C(sp3 )-H
      bond of 4 without nickel hydride formation, thus suggesting new pathways for the
      alkylation of non-activated C-H bonds.

PMID- 28758720
TI  - Probing the Crystal Plane Effect of Co3O4 for Enhanced Electrocatalytic
      Performance toward Efficient Overall Water Splitting.
AB  - Identifying effective methods to enhance the properties of catalysts is urgent to
      broaden the scanty technologies, so far. Herein, we synthesized four Co3O4
      crystals with different crystal planes and explored the crystal planes' effects
      on electrochemical water splitting through theoretical and experimental studies
      for the first time. The results illustrate that the correlation of catalytic
      activity is established as {111} > {112} > {110} > {001}. Co3O4 crystals exposed
      with {111} facets show the highest OER (oxygen evolution reaction) and HER
      (hydrogen evolution reaction) activities. Upon fabrication in an alkaline
      electrolyzer, the bifunctional {111}?{111} couple manifests the highest catalytic
      activity and satisfying durability for overall water splitting. Density
      functional theory (DFT) explains that the {111} facet possesses the biggest
      dangling bond density, highest surface energy, and smallest absolute value of
      DeltaGH*, leading to the enhanced electrocatalytic performance. This work will
      broaden our vision to improve the activity of various electrocatalysts by
      selectively exposing the specific crystal planes.

PMID- 28758719
TI  - Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictors of
      survival after heart transplantation.
AB  - AIMS: The aim of this study was to evaluate whether neutrophil-to-lymphocyte
      ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict outcome in heart
      failure (HF) patients undergoing heart transplantation (HTX). METHODS AND
      RESULTS: Data from 111 HF patients undergoing HTX 2010-2015 were retrospectively
      reviewed. NLR and PLR were calculated before HTX, immediately after HTX, and at 6
      and 24 hours. Primary endpoint was in-hospital mortality, and secondary endpoints
      were 1 year mortality and renal replacement therapy (RRT). Prognostic factors
      were assessed by multivariate analysis, and the predictive values of NLR and PLR
      for mortality were compared. The discriminatory performance for predicting in
      hospital mortality was better for NLR [area under the receiver operating
      characteristic curve (AUC) = 0.644, 95% confidence interval 0.492-0.797] than for
      PLR (AUC = 0.599, 95% confidence interval 0.423-0.776). Best cut-off value was
      2.41 for NLR (sensitivity 86%, specificity 67%) and 92.5 for PLR (sensitivity
      86%, specificity 68%). When divided according to best cut-off value, in-hospital
      mortality was significantly higher in the high NLR group (17.5% vs. 3.2%, P <
      0.05), but not in the high PLR group (16.5% vs. 6.3%, P = ns). One year mortality
      was not significantly higher for either group (37.5% vs. 6.5% for NLR; 36.7% vs.
      9.4% for PLR, P = ns for both), while RRT was significantly higher in both the
      NLR and PLR high groups (33.8% vs. 0%; 32.9% vs. 3.1%, respectively, P < 0.001).
      Multivariate analysis indicated that only high NLR (hazard ratio = 3.403, P <
      0.05) and pre-transplant diabetes (hazard ratio = 3.364, P < 0.05) were
      independent prognostic factors for 1 year mortality. CONCLUSIONS: High NLR was a
      predictor for in-hospital mortality, and an independent prognostic factor for 1
      year mortality. Both high NLR and high PLR were predictors for RRT.

PMID- 28758721
TI  - Polymer-Free Electronic-Grade Aligned Semiconducting Carbon Nanotube Array.
AB  - Conjugated polymers are used commonly to selectively sort semiconducting carbon
      nanotubes (S-CNTs) from their metallic counterparts in organic solvents. The
      polymer-wrapped S-CNTs can be easily processed from organic solvents into arrays
      of CNTs for scalable device fabrication. Though the conjugated polymers are
      essential for sorting and device fabrication, it is highly desirable to remove
      them completely as they limit the electronic properties of the device. Here, we
      use a commercially available polymer, namely, poly[(9,9-dioctylfluorenyl-2,7
      diyl)-alt-co-(6,6'-(2,2'-bipyridine))] (PFO-BPy), to sort large-diameter S-CNTs
      with ultrahigh selectivity and fabricate CNT-array-based field effect transistors
      (FETs) via a floating evaporative self-assembly (FESA) process. We report
      quantitative removal of the polymer wrapper from the FESA aligned S-CNT arrays
      using a metal-chelation-assisted polymer removal (McAPR) process. The
      implementation of this process on FESA films requires the selective thermal
      degradation of the polymer into oligomers, combined with optimization of the
      solvent type and temperature of the metal complexation reaction. Resulting S-CNT
      array FET devices show that the electronic properties of pristine CNT are
      preserved through this process. Optical microscopy, UV-vis spectroscopy, and X
      ray photoelectron spectroscopy (XPS) were used to characterize the quantitative
      polymer removal. We quantitatively describe the FET devices to analyze the
      fundamental characteristics of FETs (mobility (MU), on-conductance (Gon), and
      contact resistance (2Rc)) by comparing before and after polymer removal. The
      ability to completely remove the polymer wrapper in aligned CNT arrays without
      adversely affecting the device properties opens up applications beyond FETs into
      photovoltaics and biosensing.

PMID- 28758722
TI  - Streptomyces albus: A New Cell Factory for Non-Canonical Amino Acids
      Incorporation into Ribosomally Synthesized Natural Products.
AB  - The incorporation of noncanonical amino acids (ncAAs) with different side chains
      into a peptide is a promising technique for changing the functional properties of
      that peptide. Of particular interest is the incorporation of ncAAs into peptide
      derived natural products to optimize their biophysical properties for medical and
      industrial applications. Here, we present the first instance of ncAA
      incorporation into the natural product cinnamycin in streptomycetes using the
      orthogonal pyrrolysyl-tRNA synthetase/tRNAPyl pair from Methanosarcina barkeri.
      This approach allows site-specific incorporation of ncAAs via the read-through of
      a stop codon by the suppressor tRNAPyl, which can carry different pyrrolysine
      analogues. Five new deoxycinnamycin derivatives were obtained with three distinct
      pyrrolysine analogues incorporated into diverse positions of the antibiotic. The
      combination of partial hydrolysis and MS/MS fragmentation analysis was used to
      verify the exact position of the incorporation events. The introduction of ncAAs
      into different positions of the peptide had opposite effects on the peptide's
      biological activity.

PMID- 28758723
TI  - Critical Comparison of FRET-Sensor Functionality in the Cytosol and Endoplasmic
      Reticulum and Implications for Quantification of Ions.
AB  - Genetically encoded sensors based on fluorescence resonance energy transfer
      (FRET) are powerful tools for quantifying and visualizing analytes in living
      cells, and when targeted to organelles have the potential to define distribution
      of analytes in different parts of the cell. However, quantitative estimates of
      analyte distribution require rigorous and systematic analysis of sensor
      functionality in different locations. In this work, we establish methods to
      critically evaluate sensor performance in different organelles and carry out a
      side-by-side comparison of three different genetically encoded sensor platforms
      for quantifying cellular zinc ions (Zn2+). Calibration conditions are optimized
      for high dynamic range and stable FRET signals. Using a combination of single
      cell microscopy and a novel microfluidic platform capable of screening thousands
      of cells in a few hours, we observe differential performance of these sensors in
      the cytosol compared to the ER of HeLa cells, and identify the formation of
      oxidative oligomers of the sensors in the ER. Finally, we use new methodology to
      re-evaluate the binding parameters of these sensors both in the test tube and in
      living cells. Ultimately, we demonstrate that sensor responses can be affected by
      different cellular environments, and provide a framework for evaluating future
      generations of organelle-targeted sensors.

PMID- 28758724
TI  - Enhanced Oxygen Evolution Reaction Electrocatalysis via Electrodeposited
      Amorphous alpha-Phase Nickel-Cobalt Hydroxide Nanodendrite Forests.
AB  - We demonstrate an electrodeposition method to rapidly grow novel three
      dimensional nanodendrite forests of amorphous alpha-phase mixed nickel-cobalt
      hydroxides on stainless steel foil toward high performance electrocatalysis of
      the oxygen evolution reaction (OER). The proposed hydrogen bubble-templated,
      diffusion-limited deposition process leads to the unprecedented dendritic growth
      of vertically aligned amorphous metal hydroxides, induced by the controlled
      electrolysis of the tuned water content in the primarily alcohol-based deposition
      solution. The hierarchical nature of these binder-free, amorphous metal hydroxide
      deposits leads to their superhydrophilic nature and underwater superaerophobic
      behavior. The combination of all of these qualities leads to exemplary catalytic
      performance. When directly grown on planar stainless steel substrates, these
      nanoforests show high OER activity with overpotentials as low as ~255 mV to
      produce a current density of 10 mA cm-2 over 10 000 accelerated stability test
      cycles. This work demonstrates a novel fabrication technique that can
      simultaneously achieve a dendritic hierarchical structure, vertical alignment,
      superaerophobicity, amorphous crystal structure, and intimate contact with the
      substrate that leads to high catalytic activity with excellent durability.

PMID- 28758725
TI  - Superhydrophobic and White Light-Activated Bactericidal Surface through a Simple
      Coating.
AB  - Bacterial adhesion and proliferation on surfaces are a challenge in medical and
      industrial fields. Here, a simple one-step technique is reported to fabricate
      self-cleaning and bactericidal surfaces. White, blue, and violet paints were
      produced using titanium dioxide nanoparticles, 1H,1H,2H,2H
      perfluorooctyltriethoxysilane, crystal violet, toluidine Blue O, and ethanol
      solution. All of the painted surfaces showed superhydrophobicity in air, and even
      after hexadecane oil contamination, they retained water repellency and self
      cleaning properties. In an assay of bacterial adhesion, significant reductions
      (>99.8%) in the number of adherent bacteria were observed for all the painted
      surfaces. In bactericidal tests, the painted surfaces not only demonstrated
      bactericidal activity against Staphylococcus aureus and Escherichia coli in the
      dark but also induced very potent photosensitization (>4.4 log reduction in the
      number of viable bacteria on the violet painted surface) under white light
      illumination. The technique that we developed here is general and can be used on
      a wide range of substrates such as paper, glass, polymers, and others.

PMID- 28758726
TI  - Quaternized Polymer-Single-Walled Carbon Nanotube Scaffolds for a Chemiresistive
      Glucose Sensor.
AB  - A chemiresistive glucose sensor based on poly(4-vinylpyridine) (P4VP) and single
      walled carbon nanotube (SWCNT) composites was reported. To fabricate this glucose
      sensor, a glass substrate containing gold electrodes was treated with 3
      bromopropyltrichlorosilane to obtain a covalent bonding between the polymer-SWCNT
      composite and the glass substrate. Some of the pyridyl moieties in P4VP react
      with the surface, and the remainders were quaternized using 2-bromoethanol to
      achieve highly charged hydrophilic surface with improved biocompatibility with
      enzyme molecules. The resulting biomimetic surface was functionalized with
      glucose oxidase (GOx) by electrostatic assembly with the quaternized P4VP-SWCNT
      composite. This material displays a decrease in electrical resistance as a result
      of enzymatically liberated hydrogen peroxide produced in response to glucose,
      which increases the p-doping of the SWCNT. The sensor exhibited high selectivity
      for glucose and showed an instant response (within 3 s) to glucose.

PMID- 28758727
TI  - Structure and Barrier Properties of Multinanolayered Biodegradable PLA/PBSA
      Films: Confinement Effect via Forced Assembly Coextrusion.
AB  - Multilayer coextrusion processing was applied to produce 2049-layer film of
      poly(butylene succinate-co-butylene adipate) (PBSA) confined against poly(lactic
      acid) (PLA) using forced assembly, where the PBSA layer thickness was about 60
      nm. This unique technology allowed to process semicrystalline PBSA as confined
      polymer and amorphous PLA as confining polymer in a continuous manner. The
      continuity of PBSA layers within the 80/20 wt % PLA/PBSA layered films was
      clearly evidenced by atomic force microscopy (AFM). Similar thermal events to the
      reference films were revealed by thermal studies; indicating no diffusion of
      polymers during the melt-processing. Mechanical properties were measured for the
      multilayer film and the obtained results were those expected considering the
      fraction of each polymer, revealing the absence of delamination in the PLA/PBSA
      multinanolayer film. The confinement effect induced by PLA led to a slight
      orientation of the crystals, an increase of the rigid amorphous fraction (RAF) in
      PBSA with a densification of this fraction without changing film crystallinity.
      These structural changes allowed to strongly improve the water vapor and gas
      barrier properties of the PBSA layer into the multilayer film up to two decades
      in the case of CO2 gas. By confining the PBSA structure in very thin and
      continuous layers, it was then possible to improve the barrier performances of a
      biodegradable system and the resulting barrier properties were successfully
      correlated to the effect of confinement on the microstructure and the chain
      segment mobility of the amorphous phase. Such investigation on these
      multinanolayers of PLA/PBSA with the aim of evidencing relationships between
      microstructure implying RAF and barrier performances has never been performed
      yet. Besides, gas and water permeation results have shown that the barrier
      improvement obtained from the multilayer was mainly due to the reduction of
      solubility linked to the reduction of the free volume while the tortuosity
      effect, as usually expected, was not really observed. This work brings new
      insights in the field of physicochemical behaviors of new multilayer films made
      of biodegradable polyesters but also in interfacial processes due to the
      confinement effect induced in these multinanolayer structures obtained by the
      forced assembly coextrusion. This original coextrusion process was a very
      advantageous technique to produce eco-friendly materials with functional
      properties without the help of tie layer, additives, solvents, surface
      treatments, or inorganic fillers.

PMID- 28758728
TI  - Development of Near Infrared Spectroscopy-based Process Monitoring Methodology
      for Pharmaceutical Continuous Manufacturing Using an Offline Calibration
      Approach.
AB  - A near-infrared (NIR) calibration was developed using an efficient offline
      approach to enable a quantitative partial least-squares (PLS) chemometric model
      to measure and monitor the concentration of active pharmaceutical ingredients
      (API) in powder blends in the feed frame (FF) of a tablet press. The approach
      leveraged an offline "feed frame table," which was designed to mimic the full
      process from a NIR measurement perspective, thereby facilitating a more robust
      model by allowing more sources of variability to be included in the calibration
      by minimizing the consumption of API and other raw materials. The design of
      experiment (DOE) for the calibration was established by an initial risk
      assessment and included anticipated variability from factors related to
      formulation, process, environment, and instrumentation. A test set collected on
      the feed frame table was used to refine the PLS model. Additional fully
      independent test sets collected from the continuous drug product manufacturing
      process not only demonstrated the accuracy and precision of the model but also
      illustrated its robustness to material variability and process variability
      including mass flow rate and feed frame paddle speed. Further, it demonstrated
      that a calibration can be generated on the offline feed frame table and then
      successfully implemented on the full process equipment in a robust manner.
      Additional benefits of using the feed frame table include streamline model
      monitoring and maintenance activities in a manufacturing setting. The real-time
      monitoring enabled by this offline calibration approach can be useful as a key
      component of the control strategy for continuous manufacturing processes for drug
      products, including detecting special cause variations such as transient
      disturbances and enabling product collection/rejection based upon predetermined
      concentration limits, and may play an important role in enabling real-time
      release testing (RTRt) for manufactured pharmaceutical products.

PMID- 28758729
TI  - Improved Method of Fluorescence Quantum Yield Determination.
AB  - In the most widely used procedure for luminescence quantum yield determination,
      absorption and emission spectra are measured on two different instruments. This
      leads to errors caused by wavelength misalignment and different monochromator
      characteristics of the spectrophotometer and the spectrofluorometer. These errors
      can be avoided using a method for fluorescence quantum yield determination that
      relies on simultaneous absorption and fluorescence emission (SAFE) measurement
      using a single commercial spectrofluorometer. The method's performance is
      compared with the standard routinely used procedure for the relative quantum
      yield determination. The advantages of SAFE measurement are discussed. The
      proposed novel approach eliminates a number of potential errors in quantum yield
      determination protocol and provides higher accuracy.

PMID- 28758731
TI  - Smart D-pi-A Type Near-Infrared Abeta Probes: Effects of a Marked pi Bridge on
      Optical and Biological Properties.
AB  - To expand the scope of D-pi-A based near-infrared (NIR) probes for detecting beta
      amyloid (Abeta) plaques and to systematically explore the relationship among
      their structural characteristics, optical properties, and biological properties,
      three series of smart NIR probes with different aromatic rings and up to seven
      trans double bonds were synthesized and evaluated. Marked correlations between
      the conjugated pi system and properties of these probes, such as optical data,
      binding ability, and brain uptake, were observed. One probe, PHC-4, displayed
      improved properties as a NIR probe for the in vivo detection of Abeta plaques.

PMID- 28758730
TI  - Increasing Flexibility in Two-Dimensional Liquid Chromatography by Pulsed Elution
      of the First Dimension: A Proof of Concept.
AB  - This work demonstrates the development of an online two-dimensional liquid
      chromatography (2D-LC) method where the first dimension column is eluted by a
      sequence of pulses of increasing eluotropic strength generated by the LC pumps
      (pulsed-elution 2D-LC). Between the pulses, the first dimension is kept in a no
      elution state using low eluent strength. The eluate from the first dimension is
      actively modulated using trap columns and subsequently analyzed in the second
      dimension. We demonstrate that by tuning the length and eluotropic strength of
      the pulses, peaks with retention factors in water, kw, above 150 can be
      manipulated to elute in 3-4 pulses. The no-elution state can be kept for 1-10 min
      with only minor changes as to which and how many pulses the peaks elute in.
      Pulsed-elution 2D-LC combined with active modulation tackles three of the main
      challenges encountered in 2D-LC and specifically online comprehensive 2D-LC:
      undersampling, difficulties in refocusing, and lack of flexibility in the
      selection of column dimensions and flow rates because the two dimensions
      constrain each other. The pulsed-elution 2D-LC was applied for the analysis of a
      basic fraction of vacuum gas oil. Peak capacity was 4018 for a 540 min analysis
      and 4610 for a 1040 min analysis.

PMID- 28758732
TI  - Microwave-Assisted Synthesis of Fe3O4 Nanocrystals with Predominantly Exposed
      Facets and Their Heterogeneous UVA/Fenton Catalytic Activity.
AB  - Fe3O4 nanocrystals with five different morphologies (i.e., nanospheres, nanorods,
      nanocubes, nano-octahedrons, and nanoplates) were acquired using a simple,
      efficient, and economic microwave-assisted oxidation technique. The
      microstructure, morphology, predominant exposed facets, and iron atom local
      environment of Fe3O4 were revealed by powder X-ray diffraction (PXRD), scanning
      transmission electron microscopy (SEM), high-resolution transmission electron
      microscopy (HRTEM), X-ray photoelectron spectrometer (XPS), and Mossbauer
      spectrum. We demonstrated that the heterogeneous UVA/Fenton catalytic activities
      of Fe3O4 nanocrystals are morphology/facets dependent. Under UVA irradiation, the
      catalytic activity of the as-prepared Fe3O4 was in the sequence of nanospheres >
      nanoplates > nano-octahedrons ~ nanocubes > nanorods > nano-octahedrons (by
      coprecipitation). The dominating factor for the catalytic performance was the
      particle size and BET specific surface area; moreover, the exposed {111} facets,
      which contained more Fe2+ species, on the nanocrystal surface led to a stronger
      UVA/Fenton catalytic activity. Both *OH and O2*- radicals participated in the
      UVA/Fenton degradation process, and *OH played the dominant role. These
      morphology-controlled nanomagnetites showed great potential in applications as
      heterogeneous UVA/Fenton catalysts for effectively treating nonbiodegradable
      organic pollutants.

PMID- 28758733
TI  - Conductive Textiles via Vapor-Phase Polymerization of 3,4-Ethylenedioxythiophene.
AB  - We fabricated electrically conductive textiles via vapor-phase polymerization of
      poly(3,4-ethylenedioxythiophene) (PEDOT) layers on cotton, cotton/poly(ethylene
      terephthalate) (PET), cotton/Lycra, and PET fabrics. We then measured the
      electrical resistivity values of such PEDOT-coated textiles and analyzed the
      effect of water treatment on the electrical resistivity. Additionally, we tested
      the change in the electrical resistance of the conductive textiles under cyclic
      stretching and relaxation. Last, we characterized the uniformity and morphology
      of the conductive layer formed on the fabrics using scanning electron microscopy
      and electron-dispersive X-ray spectroscopy.

PMID- 28758734
TI  - Enhanced Visible-Light-Driven Photocatalytic Disinfection Performance and Organic
      Pollutant Degradation Activity of Porous g-C3N4 Nanosheets.
AB  - Porous g-C3N4 nanosheet (PCNS) photocatalyst with a thickness of 2.0 nm, pore
      volume of 0.61 cm3 g-1, and surface area of 190.1 m2 g-1 was prepared by a simple
      two-step template-free approach without the addition of extra reagents. Compared
      with the bulk g-C3N4 (BCN), PCNS possesses a greater number of surface reactive
      sites, improved efficiency of charge transfer, and accelerated separation of
      photogenerated electron-hole pairs. Accordingly, the visible-light-driven
      photocatalytic disinfection performance and organic pollutant degradation
      activity of PCNS are significantly enhanced. Escherichia coli (E. coli) cells can
      be killed completely by PCNS within 4 h, whereas only 77.1% of E. coli cells can
      be killed by BCN. The photodegradation rates of PCNS on methylene blue, Acid Red
      27, and bisphenol A are almost 6.4, 4.0, and 1.9 times as fast as that of BCN,
      respectively. The photocurrent intensity of PCNS is about 3.7 times in comparison
      with that of BCN. Considering the easy preparation and excellent performance,
      PCNS could be a promising and competitive visible-light-driven photocatalyst in
      the field of environment remediation.

PMID- 28758735
TI  - Electrochemical Approach for Effective Antifouling and Antimicrobial Surfaces.
AB  - Biofouling, the adsorption of organisms to a surface, is a major problem today in
      many areas of our lives. This includes: (i) health, as biofouling on medical
      device leads to hospital-acquired infections, (ii) water, since the accumulation
      of organisms on membranes and pipes in desalination systems harms the function of
      the system, and (iii) energy, due to the heavy load of the organic layer that
      accumulates on marine vessels and causes a larger consumption of fuel. This paper
      presents an effective electrochemical approach for generating antifouling and
      antimicrobial surfaces. Distinct from previously reported antifouling or
      antimicrobial electrochemical studies, we demonstrate the formation of a hydrogen
      gas bubble layer through the application of a low-voltage square-waveform pulses
      to the conductive surface. This electrochemically generated gas bubble layer
      serves as a separation barrier between the surroundings and the target surface
      where the adhesion of bacteria can be deterred. Our results indicate that this
      barrier could effectively reduce the adsorption of bacteria to the surface by
      99.5%. We propose that the antimicrobial mechanism correlates with the
      fundamental of hydrogen evolution reaction (HER). HER leads to an arid
      environment that does not allow the existence of live bacteria. In addition, we
      show that this drought condition kills the preadhered bacteria on the surface due
      to water stress. This work serves as the basis for the exploration of future self
      sustainable antifouling techniques such as incorporating it with photocatalytic
      and photoelectrochemical reactions.

PMID- 28758736
TI  - Vapor-Liquid Sol-Gel Approach to Fabricating Highly Durable and Robust
      Superhydrophobic Polydimethylsiloxane@Silica Surface on Polyester Textile for Oil
      Water Separation.
AB  - Large-scale fabrication of superhydrophobic surfaces with excellent durability by
      simple techniques has been of considerable interest for its urgent practical
      application in oil-water separation in recent years. Herein, we proposed a facile
      vapor-liquid sol-gel approach to fabricating highly durable and robust
      superhydrophobic polydimethylsiloxane@silica surfaces on the cross-structure
      polyester textiles. Scanning electron microscopy and Fourier transform infrared
      spectroscopy demonstrated that the silica generated from the hydrolysis
      condensation of tetraethyl orthosilicate (TEOS) gradually aggregated at
      microscale driven by the extreme nonpolar dihydroxyl-terminated
      polydimethylsiloxane (PDMS(OH)). This led to construction of hierarchical
      roughness and micronano structures of the superhydrophobic textile surface. The
      as-fabricated superhydrophobic textile possessed outstanding durability in
      deionized water, various solvents, strong acid/base solutions, and boiling/ice
      water. Remarkably, the polyester textile still retained great water repellency
      and even after ultrasonic treatment for 18 h, 96 laundering cycles, and 600
      abrasion cycles, exhibiting excellent mechanical robustness. Importantly, the
      superhydrophobic polyester textile was further applied for oil-water separation
      as absorption materials and/or filter pipes, presenting high separation
      efficiency and great reusability. Our method to construct superhydrophobic
      textiles is simple but highly efficient; no special equipment, chemicals, or
      atmosphere is required. Additionally, no fluorinated slianes and organic solvents
      are involved, which is very beneficial for environment safety and protection. Our
      findings conceivably stand out as a new tool to fabricate organic-inorganic
      superhydrophobic surfaces with strong durability and robustness for practical
      applications in oil spill accidents and industrial sewage emission.

PMID- 28758737
TI  - Enhanced Optical Sensitivity in Thermoresponsive Photonic Crystal Hydrogels by
      Operating Near the Phase Transition.
AB  - Photonic crystal hydrogels composed of analyte-responsive hydrogels and
      crystalline colloidal arrays have immense potential as reagentless chemical and
      biological sensors. In this work, we investigated a general mechanism to
      rationally tune the sensitivity of photonic crystal hydrogels consisting of
      stimuli-responsive polymers to small molecule analytes. This mechanism was based
      on modulating the demixing temperature of such hydrogels relative to the
      characterization temperature to in effect maximize the extent of phase separation
      behavior; thus, the volume changes in response to the target analytes. Using
      ethanol as a model analyte, we demonstrated that this mechanism led to a dramatic
      increase in the sensitivity of optically diffracting poly(N-isopropylacrylamide)
      (pNIPAM) hydrogel films that exhibit a lower critical solution temperature (LCST)
      behavior. The demixing temperature of the pNIPAM films was modulated by
      copolymerization of the films with relatively hydrophobic and hydrophilic
      comonomers, as well as by varying the ionic strength of the characterization
      solution. Our results showed that copolymerization of the films with 2.5 mol % of
      N-tert-butylacrylamide, which is hydrophobic relative to pNIPAM, enabled the
      detection limit of the pNIPAM films to ethanol to be lowered ~2-fold at 30 
      degrees C. Additionally, increasing the ionic strength of the characterization
      solution above 200 mM resulted in a dramatic increase in the extent of
      contraction of the films in the presence of ethanol. Ultimately, it was
      demonstrated that as little as 16 g/L or 2 vol % of ethanol in water could
      reliably be detected, and that the sensitivity of the films to ethanol was
      predictably greatest when operating near the phase transition, such that even
      small additions of the analyte induced the start of demixing and the collapse of
      the hydrogel. Such a mechanism may be extended to photonic crystal hydrogel
      sensors prepared from other stimuli-responsive polymers and more broadly
      exploited to enhance the utility of these sensors for a broad range of analytes.

PMID- 28758738
TI  - Enhanced Wettability and Thermal Stability of a Novel Polyethylene Terephthalate
      Based Poly(Vinylidene Fluoride) Nanofiber Hybrid Membrane for the Separator of
      Lithium-Ion Batteries.
AB  - In this study, a novel membrane for the separator in a lithium-ion (Li-ion)
      battery was proposed via a mechanically pressed process with a poly(vinylidene
      fluoride) (PVDF) nanofiber subject and polyethylene terephthalate (PET)
      microfiber support. Important physical properties, such as surface morphology,
      wettability, and heat stability were considered for the PET-reinforced PVDF
      nanofiber (PRPN) hybrid separator. Images of scanning electron microscopy (SEM)
      showed that the PRPN hybrid separator had a homogeneous pore size and high
      porosity. It can wet out in battery electrolytes completely and quickly,
      satisfying wettability requirements. Moreover, the electrolyte uptake was higher
      than that of dry-laid and wet-laid nonwovens. For heat stability, no shrink
      occurred even when the heating temperature reached 135  degrees C, demonstrating
      thermal and dimensional stability. Moreover, differential scanning calorimetry
      (DSC) showed that the PRPN hybrid separator possessed a shutdown temperature of
      131  degrees C, which is the same as conventional separators. Also, the meltdown
      temperature reached 252  degrees C, which is higher than the shutdown
      temperature, and thus can protect against internal cell shorts. The proposed PRPN
      hybrid separator is a strong candidate material for utilization in Li-ion
      batteries.

PMID- 28758739
TI  - Embedded Ag Grid Electrodes as Current Collector for Ultraflexible Transparent
      Solid-State Supercapacitor.
AB  - Flexible transparent solid-state supercapacitors have attracted immerse attention
      for the power supply of next-generation flexible "see-through" or "invisible"
      electronics. For fabrication of such devices, high-performance flexible
      transparent current collectors are highly desired. In this paper, the utilization
      of embedded Ag grid transparent conductive electrodes (TCEs) fabricated by a
      facile soft ultraviolet imprinting lithography method combined with scrap
      techniques, as the current collector for flexible transparent solid-state
      supercapacitors, is demonstrated. The embedded Ag grid TCEs exhibit not only
      excellent optoelectronic properties (RS ~ 2.0 Omega sq-1 and T ~ 89.74%) but also
      robust mechanical properties, which could meet the conductivity, transparency,
      and flexibility needs of current collectors for flexible transparent
      supercapacitors. The obtained supercapacitor exhibits large specific capacitance,
      long cycling life, high optical transparency (T ~ 80.58% at 550 nm), high
      flexibility, and high stability. Owing to the embedded Ag grid TCE structure, the
      device shows a slight capacitance loss of 2.6% even after 1000 cycles of
      repetitive bending for a bending radius of up to 2.0 mm. This paves the way for
      developing high-performance current collectors and thus flexible transparent
      energy storage devices, and their general applicability opens up opportunities
      for flexible transparent electronics.

PMID- 28758740
TI  - Yolk@Shell or Concave Cubic NiO-Co3O4@C Nanocomposites Derived from Metal-Organic
      Frameworks for Advanced Lithium-Ion Battery Anodes.
AB  - Novel hybrid metal oxides with advanced architectures are extensively pursued to
      achieve synergetic properties with respect to improved lithium-ion storage
      properties. Here, rationally designed yolk@shell or concave NiO-Co3O4@C (YNCC or
      CNCC) nanocubes have been fabricated by the simple and versatile thermolysis
      induced transformation of metal-organic frameworks (MOFs), aimed at
      simultaneously addressing the capacity fade and conductivity deficiency of metal
      oxides. The as-prepared nanocomposites with plentiful hierarchical pores
      integrate the distinct functionalities of the ternary components: NiO and Co3O4
      as the major active materials can guarantee high capacity, while carbon can
      improve the conductivity and accommodate volume changes. Benefitting from the
      intrinsic material and architecture features, the YNCC and CNCC nanocomposites
      deliver excellent electrochemical performances with high reversible specific
      capacity, superior cycling stability (803 and 870 mAh g-1 at 100 mA g-1 after 100
      cycles), and good rate capability (339 and 398 mAh g-1 at 2 A g-1) as anode
      materials for lithium-ion batteries.

PMID- 28758741
TI  - Zwitterionic Alkali-Metal Silanides of Tripodal Ligand Geometry: Synthesis,
      Structure, and Lewis Acid-Base Chemistry.
AB  - A unique family of zwitterionic alkali-metal silanides of general formula
      [Si(SiMe2OR)3M] (M-3), where M = Li, Na, K and R = CH2CH3 (M-3b), CH(CH3)2 (M
      3c), CH2CH(CH3)2 (M-3d), CH2CH2OSCH3 (M-3g), CH2CH2N(CH3)2 (M-3h), have been
      synthesized and their structures fully characterized. Compounds M-3 were prepared
      from reactions of the corresponding alkali-metal alkoxides, R'OM (R' = But, Bui;
      M = Li, Na, K) with the silanes Si(SiMe2OR)4 (2a-h), where R = CH2CH3 (b),
      CH(CH3)2 (c), CH2CH(CH3)2 (d), CH2CH2OSCH3 (g), CH2CH2N(CH3)2 (h), via selective
      Si-Si bond cleavage. Analysis of the X-ray data of Li-3a-e,g, Li-h, Li-4, Na-3a
      c,e,f,h, and K-3b,d,e,g revealed two major structural motifs in the solid state:
      infinite chain type and monomeric zwitterions. The reaction of
      Si(SiMe2OCH2CH3)3Li (Li-3b) with BPh3 in THF gave the zwitterionic Lewis acid
      base complex Ph3BSi(SiMe2OCH2CH3)3Li.THF (Li-5b). Reactions of W(CO)6 with Li-3b
      d and Na-3b,c resulted in the formation of the zwitterionic silyl tungstenate
      complexes (CO)5WSi[SiMe2OCH2CH3]3Li (Li-6b), (CO)5WSi[SiMe2OCH(CH3)2]3Li (Li-6c),
      (CO)5WSi[SiMe2OCH2CH(CH3)2)]3Li (Li-6d), (CO)5WSi(SiMe2OCH2CH3)3Na (Na-6b), and
      (CO)5WSi[SiMe2OCH(CH3)2]3Na (Na-6c), respectively. The solid-state structures of
      Li-5b and Na-6b were determined by X-ray crystallography.

PMID- 28758742
TI  - Effects of C-Glycosides from Apios americana Leaves against Oxidative Stress
      during Hyperglycemia through Regulating Mitogen-Activated Protein Kinases and
      Nuclear Factor Erythroid 2-Related Factor 2.
AB  - Main components of Apios americana leaves extract (ALE) were flavonoid C
      glycosides, including vitexin (46.7%), schaftoside (18.9%), and orientin (4.32%).
      In vitro, ALE restored glucose consumption, glucose uptake, and glycogen content
      in glucose-induced hepatic cells. Exposure of HepG2 cells to high glucose
      resulted in reactive oxygen species and O2- accumulation, while ALE alleviated
      these increases by 47 +/- 0.68 and 68 +/- 0.74%, respectively. Glucose increased
      c-Jun N-terminal kinase (JNK) and decreased extracellular signal-regulated
      kinases 1 and 2 (ERK1/2) and p38 phosphorylation, while ALE reduced p-JNK and p
      p38 but not p-ERK1/2, accompanied by nuclear factor erythroid 2-related factor 2
      (Nrf2), heme oxygenase-1, and NAD(P)H quinine oxidoreductase 1 downregulation. In
      vivo, the lifespan of Caenorhabditis elegans was more violently shortened by
      paraquat under hyperglycemia, while ALE protected this damage in N2 worms (2.6
      times extension) but not in daf-16 mutants. Furthermore, p38/PMK-1 and Nrf2/SKN-1
      expressions in worms were suppressed by glucose, which were reversed by ALE
      treatment. These results suggest that ALE prevents glucose-induced damage via
      regulating specific mitogen-activated protein kinases and Nrf2 pathways.

PMID- 28758744
TI  - Reversible Complexation of Lewis Bases to Low-Coordinate Fe(II), Co(II), and
      Ni(II) Amides: Influence of the Metal, Donor Ligand, and Amide Substituent on
      Binding Constants.
AB  - The binding constants of several monodentate Lewis bases (L) having different
      donor atoms [L = tetrahydrofuran (THF), tetrahydrothiophene (THT), pyridine, 4
      (dimethylamino)pyridine (DMAP), PMe3, PCy3, and 1,3-bis(1,3,5
      trimethylphenyl)imidazol-2-ylidene (IMes)] to the linear two-coordinate
      bis(amido) transition-metal complexes, M{N(SiMe3)Dipp}2 [M = Fe (1), Co (2), and
      Ni (3)] were determined by electronic absorption spectroscopy. In addition, 1H
      NMR spectroscopy was used to study the complexation of M{N(SiMe3)Dipp}2 by THF.
      The binding constants of the less bulky amido complexes [M{N(SiMe3)2}2]2 (M = Fe
      or Co; the nickel species is unstable) were also measured and found to bind THF
      102-103 times more strongly than M{N(SiMe3)Dipp}2. Furthermore, unlike the
      corresponding -N(SiMe3)Dipp complexes, where the iron species are more strongly
      complexed than those of cobalt, the --N(SiMe3)2 species [Co{N(SiMe3)2}2]2
      displayed a higher binding constant to THF than [Fe{N(SiMe3)2}2]2, which is in
      agreement with the stronger association of the [Co{N(SiMe3)2}2]2 dimer in
      comparison to that of its iron analogue. The binding strengths of the ligands to
      1-3 were found to be in the order of DMAP > pyridine > PMe3 > PCy3 ~ IMes > THF >
      THT, and those of the respective metals were in the order of Fe > Co > Ni.

PMID- 28758743
TI  - Influence of the Linker Length on the Cytotoxicity of Homobinuclear Ruthenium(II)
      and Gold(I) Complexes.
AB  - Dinuclear metal complexes have emerged as a promising class of anticancer
      compounds with the ability to cross-link biomolecular targets. Here, we describe
      two novel series of phosphine-linked dinuclear ruthenium(II) p-cymene and gold(I)
      complexes, in which the length of the connecting poly(ethylene glycol) chain has
      been systematically modified. The impact of the multinuclearity, lipophilicity,
      and linker length on the antiproliferative activity of the compounds on
      tumorigenic (A2780 and A2780cisR) and nontumorigenic (HEK-293) cell lines was
      assessed. The dinuclear ruthenium(II) complexes were considerably more cytotoxic
      than their mononuclear counterparts, and a correlation between the lipophilicity
      of the linker and the cytotoxicity was observed, whereas the cytotoxicity of the
      gold(I) series is independent of these factors.

PMID- 28758745
TI  - Exploring Unorthodox Dimensions for Two-Electron Atoms.
AB  - Melding quantum and classical mechanics is an abiding quest of physical chemists
      who strive for heuristic insights and useful tools. We present a surprisingly
      simple and accurate treatment of ground-state two-electron atoms. It makes use of
      only the dimensional dependence of a hydrogen atom, together with the exactly
      known first-order perturbation value of the electron-electron interaction, both
      quintessentially quantum, and the D -> infinity limit, entirely classical. The
      result is an analytic formula for D-dimensional two-electron atoms with Z >= 2.
      For D = 3 helium, it gives accuracy better than 2 millihartrees, which is better
      than current density functional theory. A kindred explicit formula for
      correlation energy exploits interpolation between D -> infinity and D = 1 or 2;
      when added to the Hartree-Fock energy, it improves accuracy for D = 3 helium to
      better than 0.1 millihartrees.

PMID- 28758746
TI  - Palladium-Catalyzed ortho-Selective C-H Chlorination of Benzamide Derivatives
      under Anodic Oxidation Conditions.
AB  - The palladium-catalyzed ortho-selective chlorination of N-quinolinylbenzamide
      derivatives with hydrochloric acid was achieved under anodic oxidation
      conditions. The use of 5,7-dichloro-8-quinolinyl group as directing group was
      effective for the selective chlorination, and the reaction was applicable to
      benzamide derivatives bearing various functional groups. Synthesis of vismodegib
      was also completed using the palladium-catalyzed electrochemical C-H chlorination
      in two different steps.

PMID- 28758747
TI  - Adsorption of Prototypical Asphaltenes on Silica: First-Principles DFT
      Simulations Including Dispersion Corrections.
AB  - In this work, we explore the interaction between some prototypical asphaltene and
      porphyrin molecules with a fully hydroxylated (0001) surface of alpha-quartz by
      means of theoretical calculations based on the density functional theory (DFT)
      under periodic boundary conditions. The influence of dispersion forces,
      adsorption geometries, and size of the side chain is analyzed. The inclusion of
      London dispersion forces is overriding as they increase the interaction by about
      1 order of magnitude. All of the considered molecules strongly interact with the
      hydroxylated surface and prefer to adsorb in a parallel position instead of
      vertically. It is also found that adsorption energy always increases with larger
      side chains because dispersion interactions also augment. Interestingly, in the
      case of porphyrin, the less stable isomer in the gas phase is the preferred one
      after adsorption, which is substantiated by a differential stabilization induced
      by the surface. Finally, we present a comparative study of the adsorption of
      these model molecules in terms of energy per area unit and energy per interacting
      pi electron.

PMID- 28758748
TI  - Correction to Ultrafast Excited-State Decays in [Re(CO)3(N,N)(L)]n+: Nonadiabatic
      Quantum Dynamics.

PMID- 28758749
TI  - Solvent-Shared Ion Pairs at the Air-Solution Interface of Magnesium Chloride and
      Sulfate Solutions Revealed by Sum Frequency Spectroscopy and Molecular Dynamics
      Simulations.
AB  - The ion distribution and ion pairing properties of Mg2+, SO42-, NO3-, and Cl- in
      the interfacial region of MgSO4, Mg(NO3)2, and MgCl2 solutions were investigated
      using vibrational sum frequency generation (VSFG) spectroscopy and molecular
      dynamics (MD) simulations. An electric field reversal relative to Mg(NO3)2 and
      MgCl2 solutions is observed at the interface of a MgSO4 solution. We show that,
      although magnesium cations are expected to have preference for bulk solvation,
      solvent-shared ion pairs (SIPs) exist in the interfacial region in which Mg2+
      cations are closer to the solution surface than sulfate anions. While interfacial
      SIPs are few, they dominate the electric field effect observed. Thus, SIPs play a
      significant role in determining the electric field direction and magnitude at the
      air-aqueous interface. In addition to impact on the fundamental understanding of
      aqueous surfaces and interfacial ion-ion interactions, these findings have
      implications for atmospheric aerosol chemistry and thundercloud electrification.

PMID- 28758750
TI  - Ultrahigh Ionic Conduction in Water-Stable Close-Packed Metal-Carbonate
      Frameworks.
AB  - Utilization of the robust metal-carbonate backbone in a series of water-stable,
      anionic frameworks has been harnessed for the function of highly efficient solid
      state ion-conduction. The compact organization of hydrophilic guest ions
      facilitates water-assisted ion-conduction in all the compounds. The dense packing
      of the compounds imparts high ion-conducting ability and minimizes the
      possibility of fuel crossover, making this approach promising for design and
      development of compounds as potential components of energy devices. This work
      presents the first report of evaluating ion-conduction in a purely metal
      carbonate framework, which exhibits high ion-conductivity on the order of 10-2 S
      cm-1 along with very low activation energy, which is comparable to highly
      conducting well-known crystalline coordination polymers or commercialized organic
      polymers like Nafion.

PMID- 28758751
TI  - Palladium-Catalyzed Carbocyclizations of Unactivated Alkyl Bromides with Alkenes
      Involving Auto-tandem Catalysis.
AB  - The development of a general catalytic system for the palladium-catalyzed
      carbocyclization of unactivated alkyl bromides with alkenes is described. This
      approach uses a commercially available bisphosphine ligand and avoids the use of
      carbon monoxide atmosphere present in prior studies involving alkyl iodides.
      Detailed mechanistic studies of the transformation are performed, which are
      consistent with auto-tandem catalysis involving atom-transfer radical cyclization
      followed by catalytic dehydrohalogenation. These studies also suggest that
      reactions involving alkyl iodides may proceed through a metal-initiated, rather
      than metal-catalyzed, radical chain process.

PMID- 28758752
TI  - Position Assignment and Oxidation State Recognition of Fe and Co Centers in
      Heterometallic Mixed-Valent Molecular Precursors for the Low-Temperature
      Preparation of Target Spinel Oxide Materials.
AB  - A series of mixed-valent, heterometallic (mixed-transition metal) diketonates
      that can be utilized as prospective volatile single-source precursors for the low
      temperature preparation of MxM'3-xO4 spinel oxide materials is reported. Three
      iron-cobalt complexes with Fe/Co ratios of 1:1, 1:2, and 2:1 were synthesized by
      several methods using both solid-state and solution reactions. On the basis of
      nearly quantitative reaction yields, elemental analyses, and comparison of metal
      oxygen bonds with those in homometallic analogues, heterometallic compounds were
      formulated as [FeIII(acac)3][CoII(hfac)2] (1),
      [CoII(hfac)2][FeIII(acac)3][CoII(hfac)2] (2), and
      [FeII(hfac)2][FeIII(acac)3][CoII(hfac)2] (3). In the above heteroleptic
      complexes, the Lewis acidic, coordinatively unsaturated CoII/FeII centers
      chelated by two hexafluoroacetylacetonate (hfac) ligands maintain bridging
      interactions with oxygen atoms of acetylacetonate (acac) groups that chelate the
      neighboring FeIII metal ion. Preliminary assignment of Fe and Co
      positions/oxidation states in 1-3 drawn from X-ray structural investigation was
      corroborated by a number of complementary techniques. Single-crystal resonant
      synchrotron diffraction and neutron diffraction experiments unambiguously
      confirmed the location of Fe and Co sites in the molecules of dinuclear (1) and
      trinuclear (2) complexes, respectively. Direct analysis in real time mass
      spectrometry revealed the presence of FeIII- and CoII-based fragments in the gas
      phase upon evaporation of precursors 1 and 2 as well as of FeIII, FeII, and CoII
      species for complex 3. Theoretical investigation of two possible "valent
      isomers", [FeIII(acac)3][CoII(hfac)2] (1) and [CoIII(acac)3][FeII(hfac)2] (1'),
      provided an additional support for the metal site/oxidation state assignment
      giving a preference of 6.48 kcal/mol for the experimentally observed molecule 1.
      Magnetic susceptibility measurements data are in agreement with the presence of
      high-spin FeIII and CoII magnetic centers with weak anti-ferromagnetic coupling
      between those in molecules of 1 and 2. Highly volatile heterometallic complexes 1
      3 were found to act as effective single-source precursors for the low-temperature
      preparation of iron-cobalt spinel oxides FexCo3-xO4 known as important materials
      for diverse energy-related applications.

PMID- 28758753
TI  - The Design of Dual-Emissive Composite Material [Zn2(HL)3]+@MOF-5 as Self
      Calibrating Luminescent Sensors of Al3+ Ions and Monoethanolamine.
AB  - Introducing another chromophore into a luminescent MOF is a potential way to
      assembling novel dual-emissive luminescent materials. Putting the chromophore,
      for which luminescence can be enhanced by Zn2+ ion, into MOF-5 by the "bottle
      around ship" strategy is a simple but efficient synthesis method to realize such
      dual-emissive materials. According to this strategy, a novel dual-emissive
      luminescent composite material [Zn2(HL)3]+@MOF-5 was constructed by loading the
      [La3(HL)2L2(NO3)3H2O] (1) (H2L = 7,7'-(ethane-1,1'-diyl)8-hydro-quinoline) into
      MOF-5, in which the [Zn2(HL)3]+ anions were transformed from 1 with the existence
      of Zn2+. The dual-emissive composite materials show excellent luminescence with
      two emissions of MOF-5 at 410 nm and [Zn2(HL)3]+ at 524 nm. Furthermore, by
      combining characteristics of MOF-5 and the guest chromophore, the composite
      material is highly selectively sensitive toward Al3+ and monoethanolamine, which
      makes [Zn2(HL)3]+@MOF-5 a potential self-calibrated fluorescence sensor.

PMID- 28758754
TI  - Cascade Amination and Acetone Monoarylation with Aryl Iodides by
      Palladium/Norbornene Cooperative Catalysis.
AB  - A palladium/norbornene cocatalyzed three-component reaction of aryl iodides, O
      benzoylhydroxylamines, and acetone is reported. o'-Aminoaryl acetones or o,o'
      diaminoaryl acetones are efficiently prepared via tandem ortho-C-H amination/ipso
      C-I alpha-arylation sequence, and the regiospecificity has been confirmed by X
      ray analysis. The proposed method addresses the condensation/amination of free-N
      H-bearing substrates in acetone monoarylations and the synthesis of extremely
      congested 2,6-disubstituted aryl acetones.

PMID- 28758755
TI  - Inflammatory Monocytes Loading Protease-Sensitive Nanoparticles Enable Lung
      Metastasis Targeting and Intelligent Drug Release for Anti-Metastasis Therapy.
AB  - Metastasis causes high mortality of breast cancer, and the inability of drug
      delivery to metastatic sites remains a crucial challenge for antimetastasis
      therapy. Herein, we report that inflammatory monocytes loading legumain-activated
      nanoparticles can actively target lung metastases and initiate metastasis
      specific intelligent drug release for antimetastasis therapy. The cytotoxic
      mertansine is conjugated to poly(styrene-co-maleic anhydride) with a legumain
      sensitive peptide and self-assembled into nanoparticles (SMNs), and then loaded
      into inflammatory monocytes to prepare the SMNs-loaded monocytes delivery system
      (M-SMNs). M-SMNs would be in living state in circulation to ensure their active
      targeting to lung metastases, and responsively damaged at the metastatic sites
      upon the differentiation of monocytes into macrophages. The anticancer drugs are
      intelligently released from M-SMNs as free drug molecules and drug-loaded
      microvesicles, resulting in considerable inhibition on the proliferation,
      migration, and invasion activities of metastatic 4T1 breast cancer cells.
      Moreover, M-SMNs significantly improve the delivery to lung metastases and
      penetrate the metastatic tumors, thus producing a 77.8% inhibition of lung
      metastases. Taken together, our findings provide an intelligent biomimetic drug
      delivery strategy via the biological properties of inflammatory monocytes for
      effective antimetastasis therapy.

PMID- 28758756
TI  - [Current possibilities to influence surgical site infection].
AB  - Infections associated with surgical procedures, also referred to as surgical site
      infections (SSIs), are the most common nosocomial infections (HAIs - Health Care
      Associated Infections) in surgery departments. Although effectively preventable
      in most cases, they are still associated with significant morbidity and
      mortality, prolonged or repeated hospitalizations and increased treatment costs.
      Therefore, compliance with applicable procedures and guidelines is essential for
      SSI prevention, which was also shown in numerous EBM studies. Relevant procedures
      and clinical guidelines involve all phases of perioperative care, covering
      preoperative patient preparation, the course of the surgical procedure itself, as
      well as post-operative care. In order to effectively reduce the risk of
      postoperative infectious complications, these proven principles and procedures
      need to be implemented into daily practice with every single surgical patient.
      Continuous monitoring of compliance with these procedures, staff education,
      recording the incidence of SSI in individual departments with regular evaluation
      and presentation of results should form an integral part of these measures.Key
      words: surgical site infection - incidence - risk factors - prevention -
      guidelines.

PMID- 28758757
TI  - [Colorectal cancer in senior patients - are we doing it well?]
AB  - INTRODUCTION: Geriatric patients form a significant part of patients with
      colorectal cancer and their numbers will probably continue to increase. Analysis
      of the quality of care provided to seniors and the results from their treatment
      are currently gaining more attention. The aim of this study was to compare how
      often standard oncological therapy is administered to seniors with colorectal
      cancer and to compare their results with younger patients along with
      complications of the therapy. METHOD: A retrospective analysis of data from 170
      patients with the diagnosis of colorectal cancer undergoing an elective curative
      surgical procedure in 2014 and 2015 was performed. Patients were divided into
      three groups according to their age (<60 years old, 6079 years old, 80 years
      old). We compared their ASA score, tumor stage (IIV), tumor localization (colon,
      rectum), incidence of serious complications grade 35 on the Clavien-Dindo scale
      and adherence to standard oncological treatment in the individual age groups.
      RESULTS: Patients 80 years and older had significantly higher ASA scores
      (p=0.0001) and significantly higher stages of tumors according to TNM-7
      classification (p=0.0413) in comparison to younger patients. Differences in
      numbers of serious complications (<60 years - 14%, 6079 years - 13%, 80 years
      30%, p=0.1499) did not reach statistical significance. Seniors underwent modified
      oncological treatment (<60 years - 6%, 6079 years - 9%, 80 years 30%, p = 0.0095)
      significantly more frequently in comparison to younger age groups. CONCLUSION:
      The application of standard multimodal oncological treatment is possible even in
      selected patients that are 80 years and older. Implementation of more reliable
      methods to objectively predict postoperative complications can become a tool to
      modify the treatment and improve the results of surgical care in elderly
      patients.Key words: geriatric patients - oncosurgery complex geriatric assessment
      colorectal cancer.

PMID- 28758758
TI  - [Thoracoscopic, epicardial ablation of atrial fibrillation using the COBRA Fusion
      system as the first part of hybrid ablation].
AB  - INTRODUCTION: Treatment of persistent and long-standing persistent atrial
      fibrillation is not successfully managed by methods of catheter ablation or
      pharmacotherapy. Hybrid ablation (i.e. combination of minimally invasive surgical
      ablation, followed by electrophysiological assessment and subsequent endocardial
      catheter ablation to complete the entire intended procedure) presents an ever
      more used and very promising treatment method. METHOD: Patients underwent
      thoracoscopic ablation of pulmonary veins and posterior wall of the left atrium
      (the box-lesion) with use of the COBRA Fusion catheter; thoracoscopic occlusion
      of the left atrial appendage using the AtriClip system was also done in later
      patients. After 23 months, electrophysiological assessment and catheter ablation
      followed. In this article we summarize a strategy of the surgical part of the
      hybrid procedure performed in our centre. We describe the surgery itself
      (including possible periprocedural complications) and we also present our short
      term results, especially with respect to subsequent electrophysiological
      findings. RESULTS: Data of the first 51 patients were analyzed. The first 25
      patients underwent unilateral ablation; the mean time of surgery was 102 min.
      Subsequent 26 patients underwent the bilateral procedure with the mean surgery
      time of 160 min. Serious complications included 1 stroke, 1 phrenic nerve palsy
      and 2 surgical re-explorations for bleeding. After 1 month, 65% of patients
      showed sinus rhythm. The box-lesion was found complete during
      electrophysiological assessment in 38% of patients and after catheter ablation,
      96% of patients were discharged in sinus rhythm. CONCLUSION: The surgical part of
      the hybrid procedure with use of the minimally invasive approach and the COBRA
      Fusion catheter is a well-feasible method with a low number of periprocedural
      complications. For electrophysiologists, it provides a very good basis for
      successful completion of the hybrid ablation.Key words: atrial fibrillation
      hybrid ablation - thoracoscopy catheter ablation electrophysiology assessment.

PMID- 28758759
TI  - [Autologous cranioplasty with a bone flap preserved subcutaneously in the
      mesogastrium].
AB  - INTRODUCTION: Cranioplasty with autologous bone flap is indicated in patients who
      have undergone decompressive craniectomy. Although it is an elective procedure,
      literature data indicate complication rates of up to 30%. The aim of this paper
      is to present our experience with cranioplasty with the patients own bone flap
      stored subcutaneously in the mesogastrium. METHODS: We retrospectively analyzed a
      set of 92 patients who had undergone cranioplasty after decompressive craniectomy
      using autologous graft preserved subcutaneously in the mesogastrium. The patients
      were clinically and radiologically examined before the surgery, and six weeks and
      one year after surgery. We evaluated the incidence of acute complications - wound
      hematoma, and late complications - infection and bone resorption. The
      postoperative cosmetic effect and patient discomfort from the stored bone flap
      also constituted an important aspect. RESULTS: The frequency of complications in
      our study group was 25%. Late complications were the most common, occurring with
      a frequency of 13%. These were mainly resorption of the bone flap (4.3%) and
      infectious complications (4.3%). Acute complications occurred with a frequency of
      10.9% in our patient group. The most serious complication was cerebral edema of
      unknown origin leading to death of the patient. Unsatisfactory cosmetic effect as
      well as discomfort at the site where the flap was stored occurred in two cases.
      CONCLUSIONS: Cranioplasty is associated with a higher risk of complications in
      comparison with other elective procedures. Nevertheless, we regard cranioplasty
      with subcutaneously preserved bone flap as an inexpensive and suitable
      alternative to cryopreservation or alloplastic materials.Key words: cranioplasty
      complications of cranioplasty autologous cranioplasty decompressive craniectomy.

PMID- 28758760
TI  - [Combined treatment of early tracheobronchopleural fistula after right tracheal
      sleeve pneumonectomy].
AB  - Extended tracheo-bronchoplastic resection for lung cancer with carinal
      involvement ranks among technically demanding procedures. Despite certain
      progress in oncological therapy, this type of resection remains the only
      potentially curative treatment of NSCLC in this localization. However, given the
      severity of complications postoperative mortality is relatively high (711%). The
      main cause of death is tracheobronchopleural fistula complicated by thoracic
      empyema, bronchopneumonia and septic shock. If ARDS (acute respiratory distress
      syndrome) develops, the mortality rate rises up to 70%. The treatment of
      tracheobronchopleural fistula is arduous, long-term and essentially
      multidisciplinary. In this case report, the authors present the case of a 58
      years old patient developing the tracheobronchopleural fistula early after
      carinal resection and sleeve pneumonectomy for a centrally localised squamous
      cell carcinoma of the right lung. The fistula was primarily sutured and secured
      using a muscular flap. For recurrence of the fistula, tissue adhesive glue was
      applied in combination with the introduction of a plastic stent, which resulted
      in healing of the tracheobronchopleural fistula.Key words: sleeve pulmonectomy
      carinal resection tracheobronchopleural fistula tracheobronchial stenting.

PMID- 28758761
TI  - [Malignant fibrous histiocytoma as a rare cause of acute limb ischemia].
AB  - Malignant fibrous histiocytoma (MFH) represents a rare malignant affection of
      heart and aorta. Its clinical presentation depends on the localisation, size,
      degree of invasion and metastasis. Previously, relatively few cases of acute
      tumour mass embolisation into the visceral and limb arterial system were
      described in the literature. In the present case study we describe a case of
      acute ischemia of both lower extremities caused by thromboembolic mass of MFH
      cells. According to literary sources this tumour type is characterized by poor
      prognosis as it was in the case of our patient.

PMID- 28758762
TI  - [Leiomyoma of external iliac vein].
AB  - Authors present a case report of a patient who was diagnosed with a tumour of
      external iliac vein. Excision of venous wall with tumour and reconstruction of
      external iliac vein with venous patch was performed. Postoperative course was
      without complication. The patient is without complications and also without signs
      of recurrence in one year follow up. Tumours of venous wall are rare. They
      originate from vena cava inferior, less often from extremity veins. The most
      frequent primary tumours of vein wall are leiomyosarcomas. Secondary tumours that
      involve venous wall are more common than primary tumours. Primary renal carcinoma
      or sarcomas of retroperitoneum represent a tumour that invades vena cava
      inferior. The diagnosis is based on CT and MRI. Surgical resection remains the
      mainstay of treatment. Chronic well collateralized obstruction is not necessary
      to reconstruct. Vena cava inferior and iliac veins are reconstructed with PTFE
      graft. Extremity veins are reconstructed using venous graft from great saphenous
      vein. Perioperative mortality after resection of vena cava inferior and pelvic
      veins is up to 6.9% major morbidity up to 33% and a fiveyear survival up to 52%.
      Patients with infrarenal involvement of vena cava have better outcomes than
      patients with involvement of retrohepatal vena cava inferior.Key words: venous
      tumour leiomyoma of venous wall.

PMID- 28758763
TI  - Psychodynamizing and existentializing cognitive-behavioral interventions: The
      case of behavioral activation (BA).
AB  - From the point of view of Cognitive-Existential Psychodynamics (Shahar, 2015a,
      2016; Shahar & Schiller, 2016; Ziv-Beiman & Shahar, 2016), active techniques
      primarily cognitive-behavioral therapy ones-might not only reduce distress but
      also bolster the therapeutic relationships and serve as powerful vehicles for
      self-discovery and growth. This, however, is contingent upon therapists' ability
      to view, and present to patients, the psychodynamic and existential nature of
      active techniques. Our focus herein is on behavioral activation, an intervention
      that consists of encouraging patients to participate in enjoyable and meaningful
      activities, in the face of depressive anhedonia. We posit that psychodynamizing
      and existentializing behavioral activation has the potential to increase
      awareness of inner multiplicity, strengthen eco-functions, assist in creating a
      "holding environment," bolster responsibility through agency, and offer a sense
      of transcendence. These benefits of behavioral activation are illustrated via a
      clinical case. (PsycINFO Database Record

PMID- 28758764
TI  - Meta-analytic review of the development of face discrimination in infancy: Face
      race, face gender, infant age, and methodology moderate face discrimination.
AB  - Infants show facility for discriminating between individual faces within hours of
      birth. Over the first year of life, infants' face discrimination shows continued
      improvement with familiar face types, such as own-race faces, but not with
      unfamiliar face types, like other-race faces. The goal of this meta-analytic
      review is to provide an effect size for infants' face discrimination ability
      overall, with own-race faces, and with other-race faces within the first year of
      life, how this differs with age, and how it is influenced by task methodology.
      Inclusion criteria were (a) infant participants aged 0 to 12 months, (b)
      completing a human own- or other-race face discrimination task, (c) with
      discrimination being determined by infant looking. Our analysis included 30 works
      (165 samples, 1,926 participants participated in 2,623 tasks). The effect size
      for infants' face discrimination was small, 6.53% greater than chance (i.e.,
      equal looking to the novel and familiar). There was a significant difference in
      discrimination by race, overall (own-race, 8.18%; other-race, 3.18%) and between
      ages (own-race: 0- to 4.5-month-olds, 7.32%; 5- to 7.5-month-olds, 9.17%; and 8-
      to 12-month-olds, 7.68%; other-race: 0- to 4.5-month-olds, 6.12%; 5- to 7.5-month
      olds, 3.70%; and 8- to 12-month-olds, 2.79%). Multilevel linear (mixed-effects)
      models were used to predict face discrimination; infants' capacity to
      discriminate faces is sensitive to face characteristics including race, gender,
      and emotion as well as the methods used, including task timing, coding method,
      and visual angle. (PsycINFO Database Record

PMID- 28758765
TI  - PTSD, mental illness, and care among survivors of sexual violence in Northern
      Uganda: Findings from the WAYS study.
AB  - BACKGROUND: Previous studies have mainly considered war-affected youth as a
      homogenous group yet several subpopulations of war-affected youth, such as
      survivors of sexual violence, exist with unique mental health problems and
      treatment needs. This study aimed to assess posttraumatic stress disorder (PTSD),
      perceptions and meaning of mental illness, and access and barriers to mental
      health care among survivors of sexual violence. METHOD: Data were collected from
      survivors of sexual violence during war (N = 181) who are participants in the
      longitudinal War-Affected Youth Survey (WAYS) study in Northern Uganda. Chi
      square tests of independence and binary logistic regression were used to compute
      participants' characteristics and assess relations between exposure to sexual
      violence and PTSD. RESULTS: Sixty-six (n = 119, 66%) reported sexual abuse: 35%
      (n = 63) of whom returned from captivity with at least 1 child, and 43% (n = 78)
      met the criteria for PTSD (Impact of Events Scale-Revised score [IES-R] >=33).
      Those who reported sexual abuse scored significantly higher on PTSD (OR = 3.23;
      95% CI [2.09, 6.93]), perceived more stigma, reported more barriers to seeking
      care, and viewed mental illness as futile and fatal compared with their peers
      without a history of sexual abuse. CONCLUSIONS: Survivors of sexual violence are
      at risk of PTSD and report major obstacles to treatment and care. More resources
      should be allocated for interventions to improve access to care for survivors of
      sexual violence. Psychoeducation to create awareness, demystify myths and public
      stigma about mental illness, and trauma-focused cognitive-behavioral therapies to
      reduce PTSD among survivors are recommended. (PsycINFO Database Record

PMID- 28758766
TI  - Main and moderating effects of temperament traits on the association between
      intimate partner violence and hazardous alcohol use in a sample of young adult
      women.
AB  - OBJECTIVE: Hazardous alcohol use is a common problem among survivors of intimate
      partner violence (IPV), although not all women who experience IPV exhibit
      hazardous alcohol use. Recent research has suggested that 1 factor that may
      influence hazardous alcohol use is temperament, although this has not yet been
      examined in the context of IPV. METHOD: In this study, we examine the main and
      moderating effects of temperament traits (constraint, negative emotionality, and
      positive emotionality) on the association between IPV and hazardous alcohol use
      in a sample of young adult women (N = 654) using a Bayesian approach to multiple
      linear regression. RESULTS: Results indicated that each temperament trait
      incrementally predicted hazardous alcohol use over and above the effects of IPV
      and other negative life events. Results further indicated that both negative
      emotionality and positive emotionality moderated the influence of IPV on
      hazardous alcohol use such that IPV was positively associated with hazardous
      alcohol use at high levels of these traits but not at low levels. CONCLUSIONS:
      Study findings extend previous research on the effects of temperament traits to
      the context of IPV, underscoring the importance of including temperament in the
      assessment of IPV survivors. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 28758767
TI  - Posttraumatic stress disorder in opioid agonist therapy: A review.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD) and opioid use disorder (OUD) co
      occur at high rates, and this co-occurrence is associated with a range of
      problems related to mental and physical health. OUD is commonly treated with
      opioid agonist therapies (OAT), which have been shown to be effective for
      reducing opiate use and related negative health consequences. Given the high
      comorbidity of PTSD and OUD, many individuals in OAT have PTSD and continue to
      experience symptoms of both disorders despite OAT treatment. In this review, the
      extant literature on PTSD among individuals in OAT is presented. METHOD: Relevant
      studies (N = 26) were identified systematically through a search of PubMed and
      PsychInfo databases. RESULTS: Literature regarding prevalence and clinical
      characteristics of patients with PTSD in OAT and treatment outcomes related to
      both OUD and PTSD is reviewed. CONCLUSION: Clinical implications of the body of
      work and recommendations for future research are provided. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 28758769
TI  - Self-affirmation attenuates death-thought accessibility after mortality salience,
      but not among a high post-traumatic stress sample.
AB  - OBJECTIVE: According to anxiety buffer disruption theory (ABDT), people function
      effectively in the world, in part, by relying on anxiety-buffer systems to
      protect against death awareness; however, traumatic experiences can overwhelm and
      disrupt those anxiety-buffer systems, leaving people unprotected from death
      awareness and at increased risk for the major symptom clusters of posttraumatic
      stress disorder (PTSD). Based on that idea, it was hypothesized that (a) when
      posttraumatic stress symptoms are low, self-affirmation (a known worldview/self
      esteem based anxiety-buffer) should prevent mortality reminders from causing
      increased death-thought accessibility (DTA); but that (b) when posttraumatic
      stress symptoms are high (indicating anxiety-buffer disruption), self-affirmation
      should fail to prevent mortality reminders from increasing DTA. METHOD: To test
      these hypotheses, participants identified in a general population prescreen
      assessment as "low posttraumatic-stress symptom" (n = 222) and "high
      posttraumatic-stress symptom" (n = 210) were reminded of death (vs. control
      topic), prompted to engage in a self-affirmation (vs. nonself-affirmation) task,
      and then asked to complete a standard assessment of death-thought accessibility
      (DTA). RESULTS: The hypotheses were confirmed, revealing that posttraumatic
      stress symptoms were associated with the ineffectiveness of anxiety-buffer system
      in protecting against increased death awareness. CONCLUSION: The present findings
      support of a foundational concept of ABDT, and point to new insights about the
      nature of PTSD and its treatment, because failure to manage death awareness is
      known to cause anxiety and exacerbate anxiety-related disorders (e.g., PTSD).
      (PsycINFO Database Record

PMID- 28758768
TI  - Characteristics of veterans and military service members who endorse causing
      harm, injury, or death to others in the military.
AB  - OBJECTIVE: The purpose of the present research was to examine the demographic and
      mental health characteristics of veterans and service members who endorsed having
      caused harm, injury, or death to another person on deployment, while taking these
      individuals' total number of other lifetime traumas into account. METHOD: Data
      for the present study were collected as part of the standard clinical evaluation
      for 228 treatment-seeking veterans and service members. RESULTS: Those who
      reported having caused harm, injury, or death to another person on deployment
      (22.4%) were more likely to be male, to have served in the Marines, to have
      served post 9/11, and to endorse other traumas commonly reported on deployment
      than those who did not endorse causing harm, injury, or death. Those who endorsed
      causing harm on deployment were less likely to have served in the Air Force, and
      to have experienced sexual assault than those who did not cause harm. Causing
      harm, injury, or death was associated with higher levels of posttraumatic stress
      disorder (PTSD), drug use, and expressive anger at the bivariate level, but was
      no longer associated with mental health problems after accounting for the number
      of other lifetime traumas. CONCLUSIONS: Examining the role of causing harm in
      isolation may lead to false conclusions. Clinicians and researchers should assess
      for veterans' and service members' entire trauma histories. (PsycINFO Database
      Record

PMID- 28758770
TI  - Adverse childhood experiences and obesity: Systematic review of behavioral
      interventions for women.
AB  - OBJECTIVE: Studies have demonstrated a relationship between adverse childhood
      experiences (ACEs) and adult obesity. Group interventions addressing the
      psychosocial sequelae of ACES using a trauma-informed approach for adults are
      well described in the literature. There is also a significant body of literature
      on the efficacy and proposed structure of interventions addressing weight
      reduction in adults. However, it is unknown how often interventions addressing
      attainment of a healthy weight incorporate a specific focus on adult women with a
      history of ACEs, including childhood abuse and trauma. METHOD: A systematic
      review of the literature was conducted using standard approaches. Two additional
      reviews used broadened inclusion criteria to identify and include group-level
      interventions that addressed intended outcomes other than obesity. Studies that
      examined the link between ACEs and obesity as a primary outcome and that provided
      a description of any potential mediating variables were also identified. The
      current literature search was conducted as the first step in a multifaceted
      approach to the development of a set of proposed research protocol designs for an
      Office on Women's Health-sponsored trauma-informed healthy weight pilot
      intervention for obese women with a history of ACEs. RESULTS: No articles
      describing interventions for the treatment of obesity or overweight women with a
      history of ACEs were identified. Eleven articles describing ACE-related
      interventions and 15 studies identifying mediators were reviewed. CONCLUSIONS:
      Intervention studies for women with ACEs, other than psychotherapy, are limited.
      Significant mediators to be considered include anxiety symptoms and internalizing
      behaviors. Specific recommendations for interventions are provided. (PsycINFO
      Database Record

PMID- 28758772
TI  - Validation of the Godin Leisure-Time Exercise Questionnaire classification coding
      system using accelerometry in multiple sclerosis.
AB  - OBJECTIVE: There have been recent efforts toward creating a health contribution
      score (HCS) from the Godin Leisure-Time Exercise Questionnaire (GLTEQ) that
      reflects public-health guidelines for levels of moderate-to-vigorous physical
      activity (MVPA). The HCS yields categories of insufficiently active (less
      substantial or low benefits), moderately active (some benefits), and active
      (substantial benefits). The present study examined the validity of the GLTEQ HCS
      and its categories as reflecting levels of MVPA in multiple sclerosis (MS).
      METHOD: The sample included 684 persons with MS. Participants wore an
      accelerometer on an elastic belt around the waist above the nondominant hip
      during the waking hours of the day over a 7-day period and completed the GLTEQ.
      RESULTS: The data analyses supported a large correlation between the GLTEQ HCS
      and accelerometer-measured MVPA, r = .46, p < .0001, but small correlations with
      accelerometer-measured light physical activity (LPA), r = .16, p < .001 and
      sedentary time, r = -.13, p = .001. There further was a large difference in
      accelerometer-measured MVPA between categories of physical activity levels (i.e.,
      insufficiently active vs. active) based on the GLTEQ HCS (d = 0.89), but small
      differences in LPA (d = 0.39) and sedentary time (d = -0.31). Those results were
      unchanged in additional data analyses accounting for LPA and sedentary behavior.
      CONCLUSIONS: The GLTEQ HCS and categories primarily reflect MVPA rather than LPA
      and sedentary behavior in persons with MS. (PsycINFO Database Record

PMID- 28758771
TI  - Childhood trauma and distress tolerance in a trauma-exposed acute-care
      psychiatric inpatient sample.
AB  - OBJECTIVE: Distress tolerance (DT; the perceived or actual ability to withstand
      negative internal states) has emerged as a promising transdiagnostic risk factor
      in clinically severe populations. However, little is known about etiological
      factors associated with the development of DT. We hypothesized that greater
      levels of childhood trauma would be associated with lower perceived and
      behavioral DT, beyond theoretically relevant covariates. METHOD: The current
      investigation evaluated several childhood trauma types (i.e., physical abuse,
      sexual abuse, emotional abuse, physical neglect, and emotional neglect) in
      relation to perceived (i.e., self-report) and behavioral DT in a sample of 87
      trauma-exposed adults in acute-care psychiatric inpatient treatment. RESULTS:
      Results of hierarchical linear regression models indicated that greater childhood
      physical abuse and emotional neglect were significantly associated with higher
      perceived DT. Greater levels of emotional abuse were associated with lower
      perceived DT, and greater physical neglect was associated with lower behavioral
      DT. CONCLUSIONS: DT may be differentially influenced by different forms of
      childhood trauma. (PsycINFO Database Record

PMID- 28758773
TI  - Disability pride protects self-esteem through the rejection-identification model.
AB  - PURPOSE/OBJECTIVE: The rejection-identification model (RIM) argues that the
      negative impacts of stigma, such as decreased self-esteem, may be mitigated when
      members of the stigmatized group choose to identify with each other rather than
      with the majority culture. A previously unstudied potential RIM stigma-reduction
      mechanism is disability pride, which views disability as a source of valuable,
      enriching, and positive experience. Impairment, personal, and environmental
      factors based on the International Classification of Functioning, Disability and
      Health (ICF) predict whether people will categorize themselves as disabled, but
      predictors of pride have received little examination. The purpose of this study
      was to (a) explore whether ICF factors predict disability pride, and (b) assess
      whether disability pride mediates a relationship between stigma and self-esteem,
      supporting RIM. Research Method/Design: Participants completed an Internet-based
      survey assessing pride, self-esteem, and ICF factors. Disability was not
      mentioned in recruitment materials to prevent selection biases. People who
      reported at least 1 impairment (n = 710) were included in analyses. RESULTS: ICF
      personal and environmental factors (stigma, social support, and being a person of
      color), but not impairment factors, predicted disability pride. Supporting RIM,
      disability pride partially mediated the relationship between stigma and self
      esteem. CONCLUSIONS/IMPLICATIONS: Disability pride is a promising way to protect
      self-esteem against stigma. Disability pride is still a rare phenomenon. Given
      that pride is associated with social support, stigma, and, to a lesser extent,
      ethnicity, but not impairment characteristics, interventions might focus on
      personal and environmental factors like these to promote pride. (PsycINFO
      Database Record

PMID- 28758774
TI  - The acquisition of simple associations as observed in color-word contingency
      learning.
AB  - Three experiments investigated the learning of simple associations in a color
      word contingency task. Participants responded manually to the print colors of 3
      words, with each word associated strongly to 1 of the 3 colors and weakly to the
      other 2 colors. Despite the words being irrelevant, response times to high
      contingency stimuli and to low-contingency stimuli quickly diverged. This high
      low difference remained quite constant over successive blocks of trials, evidence
      of stable contingency learning. Inclusion of a baseline condition-an item having
      no color-word contingency-permitted separation of the contingency learning effect
      into 2 components: a cost due to low contingency and a benefit due to high
      contingency. Both cost and benefit were quick to acquire, quick to extinguish,
      and quick to reacquire. The color-word contingency task provides a simple way to
      directly study the learning of associations. (PsycINFO Database Record

PMID- 28758775
TI  - Near-independent capacities and highly constrained output orders in the
      simultaneous free recall of auditory-verbal and visuo-spatial stimuli.
AB  - Three experiments examined the immediate free recall (IFR) of auditory-verbal and
      visuospatial materials from single-modality and dual-modality lists. In
      Experiment 1, we presented participants with between 1 and 16 spoken words, with
      between 1 and 16 visuospatial dot locations, or with between 1 and 16 words and
      dots with synchronized onsets. We found that for dual-modality lists (a) overall
      performance, initial recalls, and serial position curves were largely determined
      by the within-modality list lengths, (b) there was only a small degree of dual
      task trade-off (that was limited to the visuospatial items), and (c) there were
      strongly constrained output orders: participants tended to alternate between
      words and dots from equivalent or neighboring serial positions. In Experiments 2
      and 3, we compared lists of 6 single-modality items with dual-modality lists of 6
      words and 6 dots with synchronous or alternating onsets (Experiment 2), or random
      but asynchronous onsets (Experiment 3). In all 3 dual-modality conditions, we
      again found only a small trade-off in visuospatial (but not verbal) IFR
      performance. There were similarly highly constrained output orders with the
      synchronous and alternating onsets, and these patterns were present but
      attenuated with the randomized onsets. We propose that both auditory-verbal and
      visuospatial list items are associated with a common temporal episodic context
      that is used to guide cross-modal retrieval, and we speculate that the limited,
      asymmetric interference could arise because the less variable representations of
      the dots share only a relatively small subset of features with the more variable
      representations of the words. (PsycINFO Database Record

PMID- 28758776
TI  - Cognitive and contextual correlates of spontaneous and deliberate mind-wandering.
AB  - Individuals with greater cognitive abilities generally show reduced rates of mind
      wandering when completing relatively demanding tasks (Randall, Oswald, & Beier,
      2014). However, it is yet unclear whether elevated rates of mind-wandering among
      low-ability individuals are manifestations of deliberate, intentional episodes of
      mind-wandering because of task disengagement or lack of motivation, or to
      spontaneous, unintentional failures to maintain task-oriented attention. The
      present study examined this issue by measuring working memory capacity (WMC),
      mind-wandering during 3 relatively demanding attention control tasks, and
      contextual variables (e.g., motivation, alertness, perceptions of task
      unpleasantness). Results indicated that the relationship between WMC and mind
      wandering was primarily driven by spontaneous episodes. Lack of alertness also
      uniquely predicted more frequent spontaneous mind-wandering independently of WMC.
      Deliberate mind-wandering was primarily driven by a lack of motivation. Thus,
      cognitive and contextual factors can have distinct relationships with spontaneous
      and deliberate mind-wandering. (PsycINFO Database Record

PMID- 28758777
TI  - Reading dilemmas in a foreign language reduces both deontological and utilitarian
      response tendencies.
AB  - Moral dilemmas entail deciding whether to cause harm to maximize overall
      outcomes, such as killing 1 person to save 5. Past work has demonstrated that
      people are more willing to accept causing such outcome-maximizing harm when they
      read dilemmas in a foreign language they speak rather than their native language.
      Presumably this effect is due to foreign dilemmas inducing reduced emotional
      impact, rather than increased cognitive processing, but previous work cannot
      distinguish between these possibilities because it treats them as diametric
      opposites. In the current work, we applied process dissociation to independently
      estimate harm-rejection and outcome-maximization response tendencies underlying
      dilemma responses. These findings reveal that reading dilemmas in a foreign
      language reduces both harm-rejection and outcome-maximization inclinations. This
      pattern clarifies past work by suggesting that reading dilemmas in a foreign
      language reduces concern for all potential victims-both the fewer to be harmed
      and the majority to be saved. (PsycINFO Database Record

PMID- 28758778
TI  - The articulatory in-out effect resists oral motor interference.
AB  - People prefer words with inward directed consonantal patterns (e.g., MENIKA)
      compared to outward patterns (KENIMA), because inward (outward) articulation
      movements resemble positive (negative) mouth actions such as swallowing
      (spitting). This effect might rely on covert articulation simulations, or
      subvocalizations, since it occurs also under silent reading. We tested to what
      degree these underlying articulation simulations are disturbed by oral motor
      interference. In 3 experiments (total N = 465) we interfered with these
      articulation simulations by employing concurrent oral exercises that induce oral
      motor noise while judging inward and outward words (chewing gum, Experiment 1;
      executing meaningless tongue movements, Experiment 2; concurrent verbalizations,
      Experiment 3). Across several word stimulus types, the articulatory in-out effect
      was not modulated by these tasks. This finding introduces a theoretically
      interesting case, because in contrast to many previous demonstrations regarding
      other motor-preference effects, the covert simulations in this effect are not
      susceptible to selective motor interference. (PsycINFO Database Record

PMID- 28758780
TI  - The development of intention-based morality: The influence of intention salience
      and recency, negligence, and outcome on children's and adults' judgments.
AB  - Two experiments were conducted to investigate the influences on 4-8 year-olds'
      and adults' moral judgments. In both, participants were told stories from
      previous studies that had indicated that children's judgments are largely outcome
      based. Building on recent research in which one change to these studies' methods
      resulted in substantially more intention-based judgment, in Experiment 1 (N = 75)
      the salience and recency of intention information were increased, and in
      Experiment 2 (N = 99) carefulness information (i.e., the absence of negligence)
      was also added. In both experiments even the youngest children's judgments were
      primarily intention-based, and in Experiment 2 punishment judgments were similar
      to adults' from 5-6 years. Comparisons of data across studies and experiments
      indicated that both changes increased the proportion of intention-based
      punishment judgments-but not acceptability judgments-across age-groups. These
      findings challenge and help to explain those of much previous research, according
      to which children's judgments are primarily outcome-based. However, younger
      participants continued to judge according to outcome more than older
      participants. This might indicate that young children are more influenced by
      outcomes than are adults, but other possible explanations are discussed.
      (PsycINFO Database Record

PMID- 28758779
TI  - A longitudinal study of families formed through reproductive donation: Parent
      adolescent relationships and adolescent adjustment at age 14.
AB  - The aim of the 6th phase of this longitudinal study was to establish whether
      children born through assisted reproduction involving reproductive donation were
      at risk for psychological problems following the transition to adolescence at age
      14 and, if so, to examine the nature of these problems and the mechanisms
      involved. Eighty-seven families formed through reproductive donation, including
      32 donor insemination families, 27 egg donation families, and 28 surrogacy
      families, were compared with 54 natural conception families. Standardized
      interviews, questionnaires, and observational assessments of the quality of
      parent-adolescent relationships and adolescent adjustment were administered to
      mothers, adolescents, and teachers. The mothers in surrogacy families showed less
      negative parenting and reported greater acceptance of their adolescent children
      and fewer problems in family relationships as a whole compared with gamete
      donation mothers. In addition, less positive relationships were found between
      mothers and adolescents in egg donation families than in donor insemination
      families as rated by both mothers and adolescents. There were no differences
      between family types for the adolescents themselves in terms of adjustment
      problems, psychological well-being, and self-esteem. Longitudinal analyses showed
      no differences between family types in negative parenting from age 7 to age 14,
      and a weaker association between negative parenting and adjustment difficulties
      for gamete donation than natural conception and surrogacy families. The findings
      suggest that the absence of a genetic link between mothers and their children is
      associated with less positive mother-adolescent relationships whereas the absence
      of a gestational link does not have an adverse effect. (PsycINFO Database Record

PMID- 28758781
TI  - Development of restricted and repetitive behaviors from 15 to 77 months:
      Stability of two distinct subtypes?
AB  - A community sample of 192 parents reported on their children's restricted and
      repetitive behaviors (RRBs) at mean ages 15 months (N = 138), 26 months (N =
      191), and 77 months (N = 125) using the Repetitive Behavior Questionnaire-2 (RBQ
      2). Consistent with previous factor analytic research, 2 factors were found at
      each age: 1 comprising repetitive sensory and motor behaviors (RSM), and the
      other comprising insistence on sameness behaviors including rigidity, routines,
      and restricted interests (IS). Regression analyses indicated that RSM and IS
      subtypes develop independently. RSM at 77 months was predicted only by RSM
      behaviors at 26 months and not by IS behaviors at either 15 or 26 months nor by
      RSM behaviors at 15 months. IS at 77 months was predicted by IS behaviors at both
      15 and 26 months, but not by RSM behaviors at either 15 or 26 months. Our
      findings provide evidence that there is stability of 2 independent subtypes of
      RRBs, RSM and IS, across early childhood and that these subtypes develop
      independently of each other. (PsycINFO Database Record

PMID- 28758782
TI  - Shape up: An eye-tracking study of preschoolers' shape name processing and
      spatial development.
AB  - Learning the names of geometric shapes is at the intersection of early spatial,
      mathematical, and language skills, all important for school-readiness and
      predictors of later abilities in science, technology, engineering, and
      mathematics (STEM). We investigated whether socioeconomic status (SES) influenced
      children's processing of shape names and whether differences in processing were
      predictive of later spatial skills. Three-year-olds (N = 79) with mothers of
      varying education levels participated in an eye-tracking task that required them
      to look at named shapes. Lower SES children took longer to fixate target shapes
      and spent less time looking at them than higher SES children. Gaze variables
      measured at age 3 were predictive of spatial skills measured at age 5 even though
      the spatial measures did not require shape-related vocabulary. Early efficiency
      in the processing of shape names may contribute to the development of a
      foundation for spatial learning in the preschool years. (PsycINFO Database Record

PMID- 28758783
TI  - Mind-mindedness in parents of looked-after children.
AB  - The studies reported here aimed to test the proposal that mind-mindedness is a
      quality of personal relationships by assessing mind-mindedness in caregiver-child
      dyads in which the relationship has not spanned the child's life or in which the
      relationship has been judged dysfunctional. Studies 1 and 2 investigated
      differences in mind-mindedness between adoptive parents (ns = 89, 36) and
      biological parents from the general population (ns = 54, 114). Both studies found
      lower mind-mindedness in adoptive compared with biological parents. The results
      of Study 2 showed that this group difference was independent of parental mental
      health and could not fully be explained in terms of children's behavioral
      difficulties. Study 3 investigated differences in mind-mindedness in foster
      carers (n = 122), parents whose children had been the subject of a child
      protection plan (n = 172), and a community sample of biological parents (n =
      128). The level of mind-mindedness in foster carers and parents who were involved
      with child protection services was identical and lower than that in the community
      sample; children's behavioral difficulties could not account for the difference
      between the 2 groups of biological parents. In all 3 studies, nonbiological
      carers' tendency to describe their children with reference to preadoption or
      placement experiences was negatively related to mind-mindedness. These findings
      are in line with mind-mindedness being a relational construct. (PsycINFO Database
      Record

PMID- 28758785
TI  - Why do early mathematics skills predict later reading? The role of mathematical
      language.
AB  - A growing body of evidence indicates that the development of mathematics and
      literacy skills is highly related. The importance of literacy skills-specifically
      language-for mathematics development has been well rationalized. However, despite
      several prominent studies indicating that mathematics skills are highly
      predictive of literacy development, the reason for this relation is not well
      understood. The purpose of this study was to identify how and why early
      mathematics is predictive of early literacy development. Participants included
      125 preschool children 3-5 years old (M = 4 years 3 months). Participants were
      assessed on mathematics, literacy, and cognitive measures in both the fall and
      spring of their preschool year. Mediation analyses indicated that the relation
      between early mathematics and literacy skills is mediated by children's
      mathematical language skills. These findings suggest that, in prior research
      identifying mathematical performance as a significant predictor of later literacy
      skills, mathematical performance may have acted only as a proxy measure for more
      complex language skills such as those assessed on a mathematical language
      measure. (PsycINFO Database Record

PMID- 28758784
TI  - Number sense and mathematics: Which, when and how?
AB  - Individual differences in number sense correlate with mathematical ability and
      performance, although the presence and strength of this relationship differs
      across studies. Inconsistencies in the literature may stem from heterogeneity of
      number sense and mathematical ability constructs. Sample characteristics may also
      play a role as changes in the relationship between number sense and mathematics
      may differ across development and cultural contexts. In this study, 4,984 16-year
      old students were assessed on estimation ability, one aspect of number sense.
      Estimation was measured using 2 different tasks: number line and dot-comparison.
      Using cognitive and achievement data previously collected from these students at
      ages 7, 9, 10, 12, and 14, the study explored for which of the measures and when
      in development these links are observed, and how strong these links are and how
      much these links are moderated by other cognitive abilities. The 2 number sense
      measures correlated modestly with each other (r = .22), but moderately with
      mathematics at age 16. Both measures were also associated with earlier
      mathematics; but this association was uneven across development and was moderated
      by other cognitive abilities. (PsycINFO Database Record

PMID- 28758786
TI  - Developmental changes in infants' categorization of anger and disgust facial
      expressions.
AB  - For decades, scholars have examined how children first recognize emotional facial
      expressions. This research has found that infants younger than 10 months can
      discriminate negative, within-valence facial expressions in looking time tasks,
      and children older than 24 months struggle to categorize these expressions in
      labeling and free-sort tasks. Specifically, these older children, and even
      adults, consistently misidentify disgust expressions as anger. Although some
      scholars have hypothesized that young infants would also be unable to categorize
      anger and disgust expressions, this question has not been empirically tested. In
      addition, very little research has examined developmental changes in infants'
      perceptual categorization abilities with high arousal, within-valence emotions.
      For this reason, the current study tested 10- and 18-month-olds in a looking time
      task and found that both age groups could perceptually categorize anger and
      disgust facial expressions. Furthermore, 18-month-olds showed a heightened
      sensitivity to novel anger expressions, suggesting that, over the second year of
      life, infants' emotion categorization skills undergo developmental change. These
      findings are the first to demonstrate that young infants can categorize anger and
      disgust facial expressions and to document how this skill develops and changes
      over time. (PsycINFO Database Record

PMID- 28758788
TI  - "Functional architecture of visual emotion recognition ability: A latent variable
      approach": Correction to Lewis, Lefevre, and Young (2016).
AB  - Reports an error in "Functional architecture of visual emotion recognition
      ability: A latent variable approach" by Gary J. Lewis, Carmen E. Lefevre and
      Andrew W. Young (Journal of Experimental Psychology: General, 2016[May], Vol
      145[5], 589-602). In the article, there were several errors in Table 5. The
      correlations between the AQ-10 and both the supramodal and face-specific latent
      ability factors were set as positive. They should have been negative. The correct
      values are shown in the table provided. (The following abstract of the original
      article appeared in record 2016-13445-001.) Emotion recognition has been a focus
      of considerable attention for several decades. However, despite this interest,
      the underlying structure of individual differences in emotion recognition ability
      has been largely overlooked and thus is poorly understood. For example, limited
      knowledge exists concerning whether recognition ability for one emotion (e.g.,
      disgust) generalizes to other emotions (e.g., anger, fear). Furthermore, it is
      unclear whether emotion recognition ability generalizes across modalities, such
      that those who are good at recognizing emotions from the face, for example, are
      also good at identifying emotions from nonfacial cues (such as cues conveyed via
      the body). The primary goal of the current set of studies was to address these
      questions through establishing the structure of individual differences in visual
      emotion recognition ability. In three independent samples (Study 1: n = 640;
      Study 2: n = 389; Study 3: n = 303), we observed that the ability to recognize
      visually presented emotions is based on different sources of variation: a
      supramodal emotion-general factor, supramodal emotion-specific factors, and face-
      and within-modality emotion-specific factors. In addition, we found evidence that
      general intelligence and alexithymia were associated with supramodal emotion
      recognition ability. Autism-like traits, empathic concern, and alexithymia were
      independently associated with face-specific emotion recognition ability. These
      results (a) provide a platform for further individual differences research on
      emotion recognition ability, (b) indicate that differentiating levels within the
      architecture of emotion recognition ability is of high importance, and (c) show
      that the capacity to understand expressions of emotion in others is linked to
      broader affective and cognitive processes. (PsycINFO Database Record

PMID- 28758787
TI  - Latent profile and cluster analysis of infant temperament: Comparisons across
      person-centered approaches.
AB  - There is renewed interest in person-centered approaches to understanding the
      structure of temperament. However, questions concerning temperament types are not
      frequently framed in a developmental context, especially during infancy. In
      addition, the most common person-centered techniques, cluster analysis (CA) and
      latent profile analysis (LPA), have not been compared with respect to derived
      temperament types. To address these gaps, we set out to identify temperament
      types for younger and older infants, comparing LPA and CA techniques. Multiple
      data sets (N = 1,356; 672 girls, 677 boys) with maternal ratings of infant
      temperament obtained using the Infant Behavior Questionnaire-Revised (Gartstein &
      Rothbart, 2003) were combined. All infants were between 3 and 12 months of age (M
      = 7.85; SD = 3.00). Due to rapid development in the first year of life, LPA and
      CA were performed separately for younger (n = 731; 3 to 8 months of age) and
      older (n = 625; 9 to 12 months of age) infants. Results supported 3
      profile/cluster solutions as optimal for younger infants, and 5-profile/cluster
      solutions for the older subsample, indicating considerable differences between
      early/mid and late infancy. LPA and CA solutions produced relatively comparable
      types for younger and older infants. Results are discussed in the context of
      developmental changes unique to the end of the first year of life, which likely
      account for the present findings. (PsycINFO Database Record

PMID- 28758789
TI  - Misunderstanding the behavior priming controversy: Comment on Payne, Brown
      Iannuzzi, and Loersch (2016).
AB  - There has been considerable controversy around the limits and reproducibility of
      so-called "behavior" priming effects. Payne, Brown-Iannuzzi, and Loersch (2016)
      reported a series of 6 experiments on the effects of primes on participants' bets
      in a simulated blackjack game, and claimed that their findings not only establish
      the reality of behavior priming beyond dispute, but also demonstrate that this
      form of priming has the crucial hallmark of occurring outside participants'
      awareness and control. I describe a statistical model that does not distinguish
      automatic and controlled processes, but which nonetheless reproduces Payne et
      al.'s (2016) results and hence shows that their conclusions are unwarranted.
      Payne et al.'s (2016) experimental task and within-subjects design provide little
      insight into why some behavior priming studies have proven difficult to
      replicate. (PsycINFO Database Record

PMID- 28758790
TI  - The Accuracy of the Sysmex UF-1000i in Urine Bacterial Detection Compared With
      the Standard Urine Analysis and Culture.
AB  - CONTEXT: - Urinary tract infections are characterized by the presence of
      microbial pathogens within the urinary tract. They represent one of the most
      common infections in hospitalized and clinic patients. OBJECTIVES: - To model the
      parameters of the Sysmex UF-1000i to the gold standard, urine culture, and to
      compare the detection of dipstick leukocyte esterase and nitrates to urine
      cultures and UF-1000i results. DESIGN: - Data were compared from urine samples
      collected in sterile containers for bacterial culture and microscopic analysis.
      One sample was used to inoculate a 5% sheep blood agar and MacConkey agar plate
      using a 0.001-mL calibrated loop. The second sample was analyzed by urinalysis
      associated microscopy. The media plates were investigated for growth after 18 to
      24 hours of aerobic incubation at 37 degrees C. The second sample was analyzed
      for bacteria and leukocytes with the Sysmex UF-1000i according to the
      manufacturer's guidelines. Three definitions for culture results, sensitivity,
      and specificity at different cutoff values were calculated for the UF-1000i.
      RESULTS: - The negative predictive value for any positive culture in the adult
      population included in the study was 95.5%, and the negative predictive value for
      positive cultures containing growth of 100 000 or more colony-forming units was
      99.3% using the Sysmex UF-1000i. CONCLUSIONS: - Sysmex UF-1000i showed 98%
      sensitivity and 93.7% specificity with a 95.5% negative predictive value. Thus, a
      negative screen with the UF-1000i using defined thresholds for white blood cell
      counts and bacteria was likely to be a true negative, decreasing the need for
      presumptive antibiotics.

PMID- 28758791
TI  - Celiac Disease and Other Causes of Duodenitis.
AB  - CONTEXT: - Patients who receive an upper gastrointestinal endoscopic examination
      frequently have biopsies taken from the duodenum. Accurate interpretation of
      duodenal biopsies is essential for patient care. Celiac disease is a common
      clinical concern, but pathologists need to be aware of other conditions of the
      duodenum that mimic celiac disease. OBJECTIVE: - To review the normal histologic
      features of duodenal mucosa and describe the clinical and histologic findings in
      celiac disease and its mimics, listing the differentiating features of biopsies
      with villous atrophy and epithelial lymphocytosis. DATA SOURCES: - The study
      comprises a literature review of pertinent publications as of November 30, 2016.
      CONCLUSIONS: - Celiac disease is a common cause of abnormal duodenal histology.
      However, many of the histologic features found in the duodenal biopsy of patients
      with celiac disease are also present in other conditions that affect the small
      bowel. Diagnostic precision may be enhanced by obtaining a careful patient
      history and by ancillary laboratory testing, particularly for the presence of
      antitissue transglutaminase antibodies.

PMID- 28758792
TI  - How should we best treat patients with bloodstream infections?

PMID- 28758793
TI  - Long-term safety and efficacy of tafamidis for the treatment of hereditary
      transthyretin amyloid polyneuropathy: results up to 6 years.
AB  - BACKGROUND: The objective of the present study was to evaluate the long-term
      safety and efficacy of tafamidis in treating hereditary transthyretin amyloid
      polyneuropathy. METHODS: A prospectively planned interim analysis was conducted
      on an on-going, phase III, open-label extension study following an 18-month,
      randomized, controlled study and 12-month, open-label extension study in ATTRV30M
      patients and a single-arm, open-label study in non-ATTRV30M patients. Thirty
      seven ATTRV30M patients received placebo for 18 months, then switched to
      tafamidis and 38 ATTRV30M patients and 18 non-ATTRV30M patients continuously
      received tafamidis from day 1, up to 6 years. RESULTS: Long-term tafamidis was
      associated with a favourable safety/tolerability profile, without any unexpected
      adverse events. Patients initiating tafamidis at the start of the randomized
      study had less polyneuropathy progression versus those switching to tafamidis
      following 18 months of placebo and were less likely to progress to the next
      ambulatory stage after up to 6 years follow-up. In the patients who switched from
      placebo to tafamidis, polyneuropathy progression and deterioration in quality of
      life slowed significantly during long-term tafamidis treatment as compared with
      the previous placebo treatment. In non-ATTRV30M patients, some polyneuropathy
      progression was observed across all efficacy measures. CONCLUSIONS: These data
      provide evidence for the long-term (up to 6 years) safety and efficacy of
      tafamidis.ClinicalTrials.gov: NCT00925002.

PMID- 28758794
TI  - Helmet retention system types as a risk factor to properly attach the chin strap.
AB  - OBJECTIVES: This study aimed to determine the factors associated with the
      incorrect use of a helmet retention system (loose or open) and how often this
      happens. METHODS: This was an observational transversal study conducted in
      Curitiba, Brazil. Trained observers positioned at traffic lights collected
      information about the helmet fixation mode, the helmet model (full-face, open
      face, modular, half), and the helmet retention system model (micrometric, double
      D, fast-release). Additional data including position on the motorcycle, gender,
      and function of the motorcycle (as a work vehicle) were collected. The observers,
      collection site, and periods were randomly selected by lots. RESULTS: From a
      total of 3,050 motorcyclists, 1,807 (59.2%) had their helmets fastened correctly,
      907 (29.7%) had the retention system fastened loosely, and in 336 (11.0%), the
      retention system was completely open. Increased odds of incorrect use were
      observed for the fast-release and double-D buckles compared to the micrometrics
      buckles, with a fixed odds ratio (OR) of 4.62 (95% confidence interval [CI], 3.89
      5.51) and 3.54 (95% CI, 2.46-5.09), respectively (P <.0001). Full-face helmets
      had a higher chance of incorrect use (P <.0001), and passengers had a higher
      incidence of incorrect use of the helmet than drivers (P <.0001). CONCLUSION: An
      important risk factor related to the incorrect use of the helmet was the type of
      retention system. The helmet model and being a passenger had a secondary
      influence on incorrect use of helmets.

PMID- 28758795
TI  - Extended release delivery of erlotinib glutathione nanosponge for targeting lung
      cancer.
AB  - Systemic and uncontrolled administration of erlotinib hydrochloride (ETB) is
      associated with severe toxicity. A novel targeted and extended release nanosponge
      (NS) was synthesized from glutathione (GHS) by a one-step reaction between beta
      cyclodextrin and pyromellitic dianhydride at room temperature for delivery of ETB
      in lung cancer. Characterization studies were performed using sophisticated
      instruments. In-vitro release study was performed in the presence of incremental
      concentrations of GHS which was analyzed using HPLC. Cell cytotoxicity study was
      evaluated on human lung cancer (A549) cell lines. In-vivo tumour inhibition and
      biodistribution of ETB-loaded GHS-NS (ETB-NS) were performed on BALB/c mice. NS
      obtained was spherical, size 212 +/- 2.45 nm and high drug entrapment (92.34 +/-
      5.31%) (p < .001). In-vitro extended drug release (76.89 +/- 0.1% release at 168
      h), which was directly proportional to the concentration of GHS, demonstrated
      tumour targeting. There was enhanced in-vitro cytotoxicity and 97.5% inhibition
      in tumour growth on administering NS when compared to plain ETB (48% inhibition)
      indicating targeting of NS to the tumour site. Biodistribution study and in-vivo
      tumour growth inhibition study revealed drug release to the cancerous cell, thus
      preventing unnecessary drug exposure. ETB-NS exhibits extended drug release
      proportional to the external GSH concentration.

PMID- 28758796
TI  - On the origin of worries about modern health hazards: Experimental evidence for a
      conjoint influence of media reports and personality traits.
AB  - OBJECTIVE: Worries about health threatening effects of potential health hazards
      of modern life (e.g. electric devices and pollution) represent a growing
      phenomenon in Western countries. Yet, little is known about the causes of this
      growing special case of affective risk perceptions termed Modern Health Worries
      (MHW). The purpose of this study is to examine a possible role of biased media
      reports in the formation of MHW. DESIGN: In two experiments, we investigated
      whether typical television reports affect MHW. In Study 1, 130 participants were
      randomly assigned to a film on idiopathic environmental intolerance (IEI) or a
      control film about cystic fibrosis. In Study 2, 82 participants were randomly
      assigned to either a film on the dangers of electromagnetic fields or a control
      condition. MAIN OUTCOME MEASURES: Increases in MHW after sensational media
      reports. RESULTS: In Study 1, only participants high on the personality trait of
      absorption revealed increased MHW after watching the IEI film. In Study 2,
      specifically worries about radiation were found to be elevated after watching the
      film on the dangers of electromagnetic fields compared to the control film.
      CONCLUSION: The results of both studies reveal a significant and specific
      influence of sensational short mass media reports on MHW. The influence of
      potential moderators such as absorption remains to be clarified.

PMID- 28758797
TI  - An in vitro evaluation of the effects of a Yucca schidigera extract and chestnut
      tannins on composition and metabolic profiles of canine and feline faecal
      microbiota.
AB  - The in vitro effect of a Yucca schidigera extract (YSE) and tannins from chestnut
      wood on composition and metabolic activity of canine and feline faecal microbiota
      was evaluated. Four treatments were carried out: control diet, chestnut tannins
      (CT), YSE and CT + YSE. The YSE was added to canine and feline faecal cultures at
      0.1 g/l, while CT were added at 0.3 g/l for a 24-h incubation. A total of 130
      volatile compounds were detected by means of headspace-solid phase
      microextraction gas-chromatography/mass spectrometry analyses. Several changes in
      the metabolite profiles of fermentation fluids were found, including a decrease
      of alcohols (-19%) and esters (-42%) in feline and canine inoculum, respectively,
      which was due to the antibacterial properties of tannins. In canine inoculum,
      after 6 h, YSE + CT caused lower cadaverine concentrations (-37%), while ammonia
      (-4%) and quinolone (-27%) were reduced by addition of CT. After 24 h, the
      presence of CT resulted in a decrease of sulphur compounds, such as dimethyl
      sulphide (-69%) and dimethyl disulphide (-20%). In feline faecal cultures, after
      6 h, CT lowered the amount of indole (-48%), whereas YSE tended to decrease
      trimethylamine levels (-16%). Both in canine and feline inoculum, addition of CT
      and, to a minor extent, YSE affected volatile fatty acids patterns. In canine
      faecal cultures, CT exerted a marginal inhibitory effect on Escherichia coli
      population (-0.45 log 10 numbers of DNA copies/ml), while enterococci were
      increased (+2.06 log 10 numbers of DNA copies/ml) by YSE. The results from the
      present study show that YSE and tannins from chestnut wood exert different
      effects on the composition and metabolism of canine and feline faecal microbiota.
      In particular, the supplementation of YSE and tannins to diets for dogs and cats
      may be beneficial due to the reduction of the presence of some potentially toxic
      volatile metabolites in the animals' intestine.

PMID- 28758798
TI  - Reconfiguring diagnostic work in Danish general practice; regulation, triage and
      the secretaries as diagnostician.
AB  - Health care systems as well as bodies of medical knowledge are dynamic and change
      as the result of political and social transformations. In recent decades, health
      care systems have been subjected to a whole assemblage of regulatory practices.
      The local changes undertaken in Denmark that are being explored here are
      indicative of a long-term shift that has occurred in many welfare states intended
      to make public services in the Global North more efficient and transparent.
      Departing in prolonged field work in Danish general practice and the
      anthropological literature on audit culture, this paper suggests that the
      introduction of regulatory practices has enhanced the need for triage as a key
      organising principle. The term triage literally means separating out and refers
      to the process of sorting and placing patients in time and space. The paper
      suggests that an increasing introduction of triage feeds into a reconfiguration
      of diagnostic work, where the clinical setting is gradually becoming more
      intertwined with the governing domains of policy, and the work of the secretary
      is gradually becoming more intertwined with that of the doctor. Finally, the
      paper argues that an increasing regulation of general practice poses an ethically
      charged challenge to existing welfare politics of responsibility between the
      state and the public, as it makes it increasingly difficult to negotiate access
      to care.

PMID- 28758799
TI  - Single tracheal inoculation of Aspergillus fumigatus conidia induced
      aspergillosis in juvenile falcons (Falco spp.).
AB  - Aspergillosis is a common and life-threatening respiratory disease in raptors
      with acute and chronic courses. Among raptors, gyrfalcons (Falco rusticolus) and
      their hybrids are often declared to be highly susceptible with juvenile
      individuals being the most susceptible. However, species- and age-specific
      experimental studies are lacking and minimal infective doses (IDs) for
      Aspergillus spp. conidia are unknown.Therefore, 8-week-old, healthy gyr-hybrid
      falcons (F. rusticolus X F. cherrug) (N = 18) were experimentally infected with
      Aspergillus fumigatus using a single intratracheal inoculation with varying
      dosages of conidia (102 to 107 conidia). Over 28 days, clinical signs were
      monitored as well as haematological and serological parameters. Following
      euthanasia, necropsy, histopathology, bacteriology, and mycology were performed.
      Re-isolated fungi were compared to the inoculum using microsatellite length
      polymorphisms. During the trial, clinical signs and dyspnoea correlated
      significantly with the ID. Necropsy revealed fungal lesions in the upper and
      lower airways of 10/18 inoculated falcons, but not in the control birds. In 9/18
      inoculated falcons, fungal granulomas were confirmed in histopathology and A.
      fumigatus was re-isolated from these granulomas. Except one nasal isolate all re
      isolated fungal strains were identical to the inoculum strain. Based on mycology
      and histopathology a minimal ID of 50% was calculated to be MID50% (+/-S.E.) =
      104.52+/-0.67 for a single tracheal inoculation of A. fumigatus conidia. This
      study demonstrates for the first time that a single exposure is able to cause
      acute aspergillosis in juvenile falcons.

PMID- 28758801
TI  - Using medico-legal data to investigate fatal older road user crash circumstances
      and risk factors.
AB  - OBJECTIVE: This study used medico-legal data to investigate fatal older road user
      (ORU, aged 65 years and older) crash circumstances and risk factors relating to 4
      key components of the Safe System approach (e.g., roads and roadsides, vehicles,
      road users, and speeds) to identify areas of priority for targeted prevention
      activity. METHOD: The Coroners' Court of Victoria's (CCOV) Surveillance Database
      was searched to identify and describe the frequency and rate per 100,000
      population of fatal ORU crashes in the Australian state of Victoria for 2013
      2014. Information relating to the deceased ORU, crash characteristics and
      circumstances, and risk factors was extracted and analyzed. RESULTS: One hundred
      and thirty-eight unintentional fatal ORU crashes were identified in the CCOV
      Surveillance Database. Of these fatal ORU crashes, most involved older drivers
      (44%), followed by older pedestrians (32%), older passengers (17%), older pedal
      cyclists (4%), older motorcyclists (1%), and older mobility scooter users (1%).
      The average annual rate of fatal ORU crashes per 100,000 population was 8.1 (95%
      confidence interval [CI], 6.0-10.2). In terms of the crash characteristics and
      circumstances, most fatal ORU crashes involved a counterpart (98%), of which the
      majority were passenger cars (50%) or fixed/stationary objects (25%), including
      trees (46%) or embankments (23%). In addition, most fatal ORU crashes occurred
      close to home (73%), on-road (87%), on roads that were paved (94%), on roads with
      light traffic volume (37%), and during low-risk conditions: between 12 p.m. and 6
      p.m. (44%), on weekdays (80%), during daylight (75%), and under dry/clear
      conditions (81%). Road user (RU) error was identified by the police and/or the
      coroner for the majority of fatal crashes (55%), with a significant proportion of
      deceased ORUs deemed to have failed to yield (54%) or misjudged (41%).
      CONCLUSIONS: RU error was the most significant factor identified in fatal ORU
      crashes, which suggests that there is a limited capacity of the road system to
      fully accommodate RU errors. Initiatives related to safer roads and roadsides,
      vehicles, speed zones, as well as behavioral approaches are key areas of priority
      for targeted activity to prevent fatal ORU crashes in the future.

PMID- 28758802
TI  - Characteristics of antimuscarinic responders versus suboptimal responders in a
      randomized clinical trial of patients with overactive bladder symptoms.
AB  - OBJECTIVE: To assess the characteristics of tolterodine extended-release (ER) 4
      mg responders and suboptimal responders (<=50% decrease in UUI episodes/24 h)
      among patients with overactive bladder (OAB), including urgency urinary
      incontinence (UUI), and identify predictors of a >50% UUI response with
      fesoterodine 8 mg in tolterodine suboptimal responders. METHODS: Adult patients
      with OAB symptoms for >=6 months and >=8 micturitions, and >=2 and <15 UUI
      episodes/24 h at week -2 received open-label tolterodine ER 4 mg during a 2 week
      run-in. Suboptimal responders after tolterodine treatment (week 0) were
      randomized to fesoterodine (4 mg for 1 week, 8 mg for weeks 2-12) or placebo once
      daily. Post-hoc analyses compared the percentage change from week -2 to week 0 in
      UUI episodes/24 h in tolterodine responders versus suboptimal responders and
      identified significant predictors of a UUI response at week 12 with fesoterodine
      8 mg among tolterodine suboptimal responders. RESULTS: Of 897 patients, 610 (68%)
      were UUI suboptimal responders during the run-in period. UUI episodes/24 h at
      week -2 were similar in tolterodine responders and suboptimal responders (4.2 vs.
      4.3), but responders showed a significantly greater median percentage decrease in
      UUI episodes/24 h after tolterodine treatment at week 0 (80.0% versus 15.3%; p <
      .0001). During double-blind treatment, the percentage of patients with a UUI
      response at week 12 was significantly greater with fesoterodine (69.9%) than
      placebo (57.0%; p = .0027). Fesoterodine (vs. placebo), no previous
      antimuscarinic use before tolterodine run-in, and less UUI severity at baseline
      were significant predictors of a UUI response. CONCLUSIONS: For patients with
      OAB, including UUI, who were treated initially with tolterodine and showed a
      suboptimal UUI response, nearly 70% demonstrated a UUI response with second-line
      fesoterodine 8 mg. No antimuscarinic use before tolterodine and fewer baseline
      UUI episodes were significant predictors of a UUI response with fesoterodine.

PMID- 28758800
TI  - Dosing antibiotics in neonates: review of the pharmacokinetic data.
AB  - Antibiotics are often used in neonates despite the absence of relevant dosing
      information in drug labels. For neonatal dosing, clinicians must extrapolate data
      from studies for adults and older children, who have strikingly different
      physiologies. As a result, dosing extrapolation can lead to increased toxicity or
      efficacy failures in neonates. Driven by these differences and recent legislation
      mandating the study of drugs in children and neonates, an increasing number of
      pharmacokinetic studies of antibiotics are being performed in neonates. These
      studies have led to new dosing recommendations with particular consideration for
      neonate body size and maturation. Herein, we highlight the available
      pharmacokinetic data for commonly used systemic antibiotics in neonates.

PMID- 28758803
TI  - Assessment of left atrium and diastolic dysfunction in patients with hypertensive
      retinopathy: A real-time three-dimensional echocardiography-based study.
AB  - The fundoscopic examination of hypertensive patients, which is established
      hypertension-related target organ damage (TOD), tends to be underutilized in
      clinical practice. We sought to investigate the relationship between retinal
      alterations and left atrium (LA) volumes by means of real-time three-dimensional
      echocardiography (RT3DE). Our population consisted of 88 consecutive essential
      hypertensive patients (age 59.2 +/- 1.2 years, 35 males). All subjects underwent
      a fundoscopy examination and were distributed into four groups according to the
      Keith-Wagener-Barker (KWB) classification. The four groups (KWB grades 0-3:
      including 26, 20, 26, and 16 patients, respectively) did not differ with regard
      to age, gender, or metabolic profile. There were no significant differences
      between groups with regard to parameters reflecting LV systolic function and
      diastolic dysfunction (DD) in two-dimensional echocardiography (2DE).
      Nevertheless, patients in the higher KWB category had higher values of LA volumes
      (LA maximal volume index, LA minimal volume index, preatrial contraction volume
      index, LA total stroke volume index, LA active stroke volume index, p < 0.001)
      regarding RT3DE. There is also a significant relationship between LA active
      stroke volume index (ASVI) and duration of hypertension (HT) (r: 0.68, p <
      0.001). In the logistic regression analysis, ASVI was independent predictors of
      LV DD in patients with arterial hypertension (HT). Patients with arterial HT were
      found to have increased LA volumes and impaired diastolic functions. Assessment
      of the arterial HT patient by using RT3DE atrial volume analysis may facilitate
      early recognition of TOD, which is such a crucial determinant of cardiovascular
      mortality and morbidity.

PMID- 28758804
TI  - Rapamycin mitigates erythrocyte membrane transport functions and oxidative stress
      during aging in rats.
AB  - Erythrocyte membrane is a suitable model to study various metabolic and
      physiological functions as it undergoes variety of biochemical changes during
      aging. An age-dependent modulatory effect of rapamycin on erythrocyte membrane
      functions is completely unknown. Therefore, the present study was undertaken to
      investigate the effect of rapamycin on age-dependent impaired activities of
      transporters/exchangers, altered levels of redox biomarkers, viz. protein
      carbonyl (PC), lipid hydroperoxides (LHs), total thiol (-SH), sialic acid (SA)
      and intracellular calcium ion [Ca2+]i, and osmotic fragility of erythrocyte
      membrane. A significant reduction in membrane-bound activities of Na+/K+-ATPase
      (NKA) and Ca2+-ATPase (PMCA), and levels of -SH and SA was observed along with a
      simultaneous induction in Na+/H+ exchanger (NHE) activity and levels of [Ca2+]i,
      PC, LH and osmotic fragility in old-aged rats. Rapamycin was found to be a
      promising age-delaying drug that significantly reversed the aging-induced
      impaired activities of membrane-bound ATPases and altered levels of redox
      biomarkers.

PMID- 28758805
TI  - Immunoaffinity techniques coupled to mass spectrometry for the analysis of human
      peptide hormones: advances and applications.
AB  - INTRODUCTION: The accurate and comprehensive determination of peptide hormones
      from biological fluids has represented a considerable challenge to analytical
      chemists for decades. Besides long-established bioanalytical ligand binding
      assays (or ELISA, RIA, etc.), more and more mass spectrometry-based methods have
      been developed recently for purposes commonly referred to as targeted proteomics.
      Eventually the combination of both, analyte extraction by immunoaffinity and
      subsequent detection by mass spectrometry, has shown to synergistically enhance
      the test methods' performance characteristics. Areas covered: The review provides
      an overview about the actual state of existing methods and applications
      concerning the analysis of endogenous peptide hormones. Here, special focus is on
      recent developments considering the extraction procedures with immobilized
      antibodies, the subsequent separation of target analytes, and their detection by
      mass spectrometry. Expert commentary: Key aspects of procedures aiming at the
      detection and/or quantification of peptidic analytes in biological matrices have
      experienced considerable improvements in the last decade, particularly in terms
      of the assays' sensitivity, the option of multiplexing target compounds,
      automatization, and high throughput operation. Despite these advances and
      progress as expected to be seen in the near future, immunoaffinity purification
      coupled to mass spectrometry is not yet a standard procedure in routine analysis
      compared to ELISA/RIA.

PMID- 28758806
TI  - The patient perspective on the use of information and communication technologies
      and e-health in rehabilitation.
AB  - INTRODUCTION: Success of e-health relies on the extent to which the related
      technology, such as the electronic device, is accepted by its users. However,
      there has been limited research on the patients' perspective on use of e-health
      related technology in rehabilitation care. OBJECTIVE: To explore the usage of
      common electronic devices among rehabilitation patients with access to email and
      investigate their preferences regarding their usage in rehabilitation. METHODS:
      Adult patients who were admitted for inpatient and/or outpatient rehabilitation
      and were registered with an email address were invited to complete an electronic
      questionnaire regarding current and preferred use of information and
      communication technologies in rehabilitation care. RESULTS: 190 out of 714
      invited patients completed the questionnaire, 94 (49%) female, mean age 49 years
      (SD 16). 149 patients (78%) used one or more devices every day, with the most
      frequently used devices were: PC/laptop (93%), smartphone (57%) and tablet (47%).
      Patients mostly preferred to use technology for contact with health professionals
      (mean 3.15, SD 0.79), followed by access to their personal record (mean 3.09, SD
      0.78) and scheduling appointments with health professionals (mean 3.07, SD 0.85).
      CONCLUSION: Most patients in rehabilitation used one or more devices almost every
      day and wish to use these devices in rehabilitation. Implications for
      Rehabilitation In a sample of 190 patients in rehabilitation with access to
      email, almost all patients used one or more electronic devices almost every day
      of the week, with the most frequently used devices were: a PC/laptop, smartphone
      and tablet. Most of the patients wish to incorporate electronic devices in their
      rehabilitation process and prefer to use those devices to have insight in their
      health record, communication with peers and scheduling appointments with health
      professionals. To better assist patients with e-health in rehabilitation care in
      the future, preferences could be implemented in rehabilitation care by using the
      most commonly used devices.

PMID- 28758807
TI  - Correction to: Nakajima and Oda, Ketonuria may be associated with low serum
      amylase independent of body weight and glucose metabolism.

PMID- 28758809
TI  - Development and testing an online near-infrared spectroscopy brain-computer
      interface tailored to an individual with severe congenital motor impairments.
AB  - PURPOSE: For non-verbal individuals, brain-computer interfaces (BCIs) are a
      potential means of communication. Near-infrared spectroscopy (NIRS) is a brain
      monitoring modality that has been considered for BCIs. To date, limited NIRS-BCI
      testing has involved online classification, particularly with individuals with
      severe motor impairments. MATERIALS AND METHODS: We tested an online NIRS-BCI
      developed for a non-verbal individual with severe congenital motor impairments.
      The binary BCI differentiated categorical verbal fluency task (VFT) performance
      and rest using prefrontal measurements. The participant attended five sessions,
      the last two of which were online with classification feedback. RESULTS: An
      online classification accuracy of 63.33% was achieved using a linear discriminant
      classifier trained on a four-dimensional feature set. An offline, cross
      validation analysis of all data yielded an optimal adjusted classification
      accuracy of 66.6 +/- 9.11%. Inconsistent functional responses, contradictory
      effects of feedback, participant fatigue and motion artefacts were identified as
      challenges to online classification specific to this participant. CONCLUSIONS:
      Results suggest potential in using an NIRS-BCI controlled by the VFT in instances
      of severe congenital impairments. Further testing with users with severe
      disabilities is necessary. Implications for Rehabilitation Brain-computer
      interfaces (BCIs) can provide a non-motor based means of communication for
      individuals with severe motor impairments. Near-infrared spectroscopy (NIRS) is a
      haemodynamic-based brain-imaging modality used in BCIs. To date, NIRS-BCIs have
      not been thoroughly tested with potential target users. This case study shows
      that NIRS-BCIs may offer a means of practical communication for individuals with
      severe congenital impairments and continued exploration is advisable.

PMID- 28758808
TI  - Anti-Mullerian hormone in type 2 and gestational diabetes during the second half
      of pregnancy: relationship with sexual steroid levels and metabolic parameters.
AB  - Hyperandrogenemia and hyperinsulinemia are observed in women with diabetes during
      pregnancy. The effect of diabetes on anti-Mullerian hormone (AMH) levels during
      pregnancy is unclear. The aim of this study was to determine the AMH levels in
      women with type 2 diabetes (T2D) and gestational diabetes (GD) compared to
      healthy (C) pregnant women during the second half of gestation. A prospective
      study of 69 pregnant women with T2D (N: 21), GD (N: 24) and C (N: 24) were
      followed up during the second half of pregnancy. Clinical assessments and blood
      samples were collected at 26.7 (25-27.8); 34 (32-34.9) and 37.5 (37-40) weeks of
      gestation. AMH, sexual steroids, insulin, homeostatic model assessment of insulin
      resistance, HbA1c levels were measured. AMH levels were similar between T2D, GD
      and C (p = .07). A decline of AMH levels during the second half of gestation was
      observed in the three groups (p < .0001). AMH levels were negatively associated
      with age (p < .001). A positive association between AMH and testosterone (p <
      .05) was found in all groups. A progressive decline of AMH levels is observed in
      diabetic and healthy women during the second half of pregnancy. Testosterone
      levels are an independent factor that influences AMH levels during pregnancy.
      However, AMH levels are not affected by the presence of diabetes during
      gestation.

PMID- 28758810
TI  - Cost analysis of leuprorelin acetate in Japanese prostate cancer patients:
      comparison between 6-month and 3-month depot formulations.
AB  - AIMS: This study aimed to evaluate the economic value for leuprorelin acetate 6
      month depot compared with leuprorelin acetate 3-month depot from a societal
      perspective in Japanese prostate cancer patients. METHODS: The cost analysis
      estimated the reduction in direct and indirect costs as well as intangible costs
      saved by having one less injection. Claims data were used for the analyses of
      direct and indirect costs reduction. A discrete choice experiment based on a web
      based survey estimated the monetary value of the intangible costs for one
      injection. Another web-based survey of prostate cancer patients, who had received
      treatment with leuprorelin acetate injections, was carried out to calibrate the
      results of the discrete choice experiment. RESULTS: Reductions in medical costs
      and loss of productivity for having one less injection in prostate cancer
      patients receiving leuprorelin acetate were JPY 5,670 and JPY 1,723,
      respectively. Intangible costs saved by using a 6-month depot formulation instead
      of a 3-month depot formulation for the injection of leuprorelin acetate were
      estimated to be JPY 19,872, including the values for a reduction in pain (JPY
      3,131), injection site reactions (JPY 11,545), waiting time (JPY 9,479), and
      subtracting the value of medical consultation (JPY 4,283). The total cost
      reduction for having one less injection was JPY 27,265. LIMITATIONS: The
      respondents from the internet panel provided by a survey company are not
      necessarily a representative population of Japanese society. CONCLUSIONS:
      Leuprorelin acetate 6-month depot has an advantage in monetary value in the
      reduction in medical costs, loss of productivity, and intangible costs for having
      one less injection in prostate cancer patients compared with leuprorelin acetate
      3-month depot. In the costs for treating with leuprorelin acetate, the percentage
      of intangible costs might not be negligible. The intangible costs will probably
      be actively evaluated to proceed to patient-centered healthcare in society.

PMID- 28758812
TI  - Combination with CK19 Might Increase the Prognostic Power of Hep Par 1 in
      Hepatocellular Carcinoma after Curative Resection.
AB  - PURPOSE: Hepatocyte Paraffin 1 (Hep Par 1) and cytokeratin 19 (CK19) were shown
      to be associated with post-surgical prognosis of hepatocellular carcinoma (HCC).
      However, further validation might be needed. Besides, their combined evaluation
      has not been reported. The present study was designed to address the issues.
      MATERIALS AND METHODS: Expressions of Hep Par 1 and CK19 were detected using
      tissue microarray-based immunohistochemical staining in 79 patients with HCC
      underwent curative hepatectomy. Their associations with cliniopathologic
      variables, overall and recurrence-free survival were analyzed. RESULTS: Hep Par 1
      was highly expressed in 61 patients (77.2%), whereas CK19 was positive in 8
      patients (10.1%). Moreover, expressions of these two proteins were all associated
      with tumor-node-metastasis (TNM) stage and vascular invasion. It was found that
      high Hep Par 1 expression was univariately associated with good overall and
      recurrence-free survival, while CK19 was marginally prognostic. Also in
      univariate analyses, combination of the two markers more effectively predicted
      for long-term prognosis in HCC than Hep Par 1 did. However, neither Hep Par 1 nor
      Hep Par 1/CK19 was multivariately significant. Finally, Hep Par 1/CK19 combined
      with TNM stage might obtain more satisfactory outcome prediction, especially for
      overall survival. CONCLUSIONS: Combination of CK19 with Hep Par 1 might have
      higher prognostic power, which might be further improved by adding TNM stage,
      than Hep Par 1 alone, in resected HCC. Of course, subsequent confirmation is
      necessary.

PMID- 28758811
TI  - Novel pathologic scoring tools predict end-stage kidney disease in light chain
      (AL) amyloidosis.
AB  - BACKGROUND AND OBJECTIVES: Light chain (AL) amyloidosis frequently involves the
      kidney, causing significant morbidity and mortality. A pathologic scoring system
      with prognostic utility has not been developed. We hypothesized that the extent
      of amyloid deposition and degree of scarring injury on kidney biopsy, could
      provide prognostic value, and aimed to develop pathologic scoring tools based on
      these features. METHODS: This is a case-control study of 39 patients treated for
      AL amyloidosis with biopsy-proven kidney involvement at a large academic medical
      center. Our novel scoring tools, composite scarring injury score (CSIS) and
      amyloid score (AS) were applied to each kidney biopsy. The primary outcome was
      progression to dialysis-dependent end-stage kidney disease (ESKD) using a 12
      month landmark analysis. RESULTS: At 12 months, nine patients had progressed to
      ESKD. Patients with an AS >=7.5 had a significantly higher cumulative incidence
      of ESKD than those with AS <7.5 (p = .04, 95% CI 0.13-0.64). CONCLUSIONS: Using a
      12-month landmark analysis, AS correlated with progression to ESKD. These data
      suggest that a kidney biopsy, in addition to providing diagnostic information,
      can be the basis for a pathologic scoring system with prognostic significance.

PMID- 28758813
TI  - Medication safety knowledge, attitudes and practices among community pharmacists
      in Lebanon.
AB  - BACKGROUND: The effectiveness of a national post-marketing surveillance program
      depends directly on the active participation of all health professionals. There
      is no current comprehensive and active pharmacovigilance program available in
      Lebanon. OBJECTIVES: To assess the knowledge, attitudes, and practices (KAP)
      among community pharmacists in Lebanon with respect to potential
      pharmacovigilance and adverse-drug-reaction reporting in Lebanon. METHODS: A
      cross-sectional descriptive study, using a self-administered KAP questionnaire
      and conducted between March and July 2016, included 1857 pharmacists practicing
      in community settings. Statistical analysis included chi2 test for dichotomous or
      multinomial qualitative variables, and Wilcoxon test for quantitative variables
      with non-homogeneous variances or non-normal distribution. RESULTS: The majority
      of responders had good knowledge concerning the concept and purpose of
      pharmacovigilance as well as adverse drug reactions (how to report these/the
      importance of reporting adverse events/the definition of an adverse event and
      pharmacovigilance). Concerning community pharmacists' attitudes and practice
      towards pharmacovigilance, the majority described having a positive attitude
      towards their role in adverse drug reaction reporting and this activity was even
      seen as one of their core duties. The questionnaire revealed a lack of practice
      and training regarding pharmacovigilance. Nonetheless, the pharmacists agreed on
      the Order of Pharmacists in Lebanon and the Ministry of Health's role in
      promoting this practice and helping them be more involved in reporting adverse
      drug reactions (ADRs). The pharmacists thought that they are well positioned
      regarding patient-safety practice in their pharmacies and the results were not
      statistically different between pharmacy employers and employees. CONCLUSION:
      Lebanese pharmacists have the required knowledge and positive attitude to start
      reporting ADRs, were aware of ADRs occurring with various medicines post
      marketing, yet were currently not able to disseminate this information widely or
      to record it centrally, emphasizing the importance of establishing a national ADR
      reporting system.

PMID- 28758814
TI  - Overweight in childhood and adolescence: Does it lead to airway
      hyperresponsiveness in adulthood?
AB  - BACKGROUND: Obesity is increasing worldwide among children and adolescents, and
      has been associated with an increased incidence of asthma. However, the
      mechanisms underlying this association are incompletely understood. OBJECTIVE: In
      this cohort study we aimed to investigate whether being overweight in childhood
      and adolescence is associated with an increased risk of airway
      hyperresponsiveness (AHR), a hallmark of asthma, in early adulthood. METHODS: Of
      527 subjects from a random population sample of children and adolescents (7-17
      years) examined at baseline, a total of 184 subjects completed the follow-up
      visit 20 years later and were included in the present analysis. Both visits
      included assessment of height and weight, case history and spirometry. At both
      visits, bronchial provocation tests were performed using either histamine
      (baseline) or methacholine (follow-up). In addition, fractional exhaled nitric
      oxide (FeNO) was measured at follow-up. RESULTS: No significant difference in the
      prevalence of AHR at follow-up was found between subjects who were overweight or
      obese at baseline visit (n = 26) (pediatric definition, body mass index >=
      85%percentile) and normal weight subjects (n = 158) (positive bronchial
      provocation tests: 15.4% vs. 22.2%, respectively, p = 0.35). Likewise, follow-up
      FeNO levels did not differ significantly between subjects who were lean and those
      who were overweight or obese at baseline (geometric mean (95% confidence interval
      [CI]) 15.1 (13.7, 16.6) parts per billion (ppb) versus 13.0 (10.6, 15.9) ppb, p =
      0.23). CONCLUSION: In children and adolescents, being obese or overweight seems
      not to be associated with an increased risk of AHR or increased FeNO levels in
      early adulthood.

PMID- 28758815
TI  - Physicochemical interaction mechanism between nanoparticles and tetrasaccharides
      (stachyose) during freeze-drying.
AB  - Nanoparticle suspensions are thermodynamically unstable and subject to
      aggregation. Freeze-drying on addition of saccharides is a useful method for
      preventing aggregation. In the present study, tetrasaccharides (stachyose) was
      employed as an additive. In addition, we hypothesize the interactive mechanism
      between stachyose and the nanoparticles during freeze-drying for the first time.
      The mean particle size of the rehydrated freeze-dried stachyose-containing
      nanoparticles (104.7 nm) was similar to the initial particle size before freeze
      drying (76.8 nm), indicating that the particle size had been maintained. The mean
      particle size of the rehydrated normal-dried stachyose-containing nanoparticles
      was 222.2 nm. The powder X-ray diffraction of the freeze-dried stachyose
      containing nanoparticles revealed a halo pattern. The powder X-ray diffraction of
      the normally dried stachyose-containing nanoparticles produced mainly a halo
      pattern and a partial peak. These results suggest an interaction between the
      nanoparticles and stachyose, and that this relationship depends on whether the
      mixture is freeze-dried or dried normally. In the case of normal drying, although
      most molecules cannot move rapidly thereby settling irregularly, some stachyose
      molecules can arrange regularly leading to some degree of crystallization and
      potentially some aggregation. In contrast, during freeze-drying, the moisture
      sublimed, while the stachyose molecules and nanoparticles were immobilized in the
      ice. After sublimation, stachyose remained in the space occupied by water and
      played the role of a buffer material, thus preventing aggregation.

PMID- 28758817
TI  - The validity, reliability, and responsiveness of the modified Iowa Level of
      Assistance scale in hospitalized older adults in subacute care.
AB  - OBJECTIVE: The objective of this study was to investigate the psychometric
      properties of the Modified Iowa Level of Assistance scale in hospitalized older
      adults in subacute care. DESIGN: A cohort, measurement-focused study.
      PARTICIPANTS AND SETTING: Fifty-eight older adults, aged 65 years and older, were
      recruited from a subacute rehabilitation hospital. METHODS: Inter-rater
      reliability was established by having two physiotherapists independently assess
      each participant within 24-h of each other. Construct validity was established
      using "known-groups" validity, while concurrent validity was also examined by
      correlating modified Iowa Level of Assistance scores with the Elderly Mobility
      Scale. Responsiveness was assessed by examining the difference in modified Iowa
      Level of Assistance scores from admission to discharge. RESULTS: The mean age of
      participants was 82.8 years (SD 7.5; range 68-97). The modified Iowa Level of
      Assistance scale was found to be reliable, valid, and responsive in this sample
      of hospitalized older adults. It had excellent inter-rater reliability
      (intraclass correlation coefficient [2,1] 0.96; 95% confidence intervals (CI)
      0.93, 0.98) and no systematic differences across the range of scores. The scale
      displayed a mean difference between two known groups of 11.4 points and
      correlated significantly and negatively with the Elderly Mobility Scale
      (Spearman's rho - 0.90). The modified Iowa Level of Assistance score also changed
      significantly over the course of the hospital admission with an effect size of
      1.2. CONCLUSIONS: The modified Iowa Level of Assistance scale is a valid measure
      with excellent inter-rater reliability in hospitalized older adults. It is
      responsive to functional change during hospital admission and may be useful for
      routine outcome assessment for hospitalized older adults in subacute care.
      Implications for Rehabilitation The mILOA scale is a valid, reliable, and
      responsive outcome measure that can be used to quantify the gait and mobility
      impairments in hospitalized older adults in subacute care. For optimal
      reliability and responsiveness, consistent administration of the mILOA scale will
      be required particularly for higher level mobility tasks such as negotiating a
      step.

PMID- 28758816
TI  - The interactions of cephalosporins on polyol pathway enzymes from sheep kidney.
AB  - CONTEXT: Cephalosporins are derived from the fungus Acremonium. Due to their
      strong bactericidal ability, these drugs have to a wide usage in medicine.
      OBJECTIVE: An investigation of the effects on sheep renal aldose reductase (AR)
      and sorbitol dehydrogenase (SDH) of cefoperazone, cefazolin, cefuroxime,
      ceftazidime and ceftriaxone as cephalosporin drugs was carried out in the present
      study. METHODS: AR and SDH were purified from sheep kidney by ion exchange, gel
      filtration and affinity methods with approximately 219- and 484-fold,
      respectively. Some kinetic properties of the enzymes were determined such as
      optimal pH, optimal ionic strength, optimal temperature, stable pH, Km and Vmax.
      IC50 values of the drugs were found for each enzyme. RESULTS: While the AR was
      inhibited by all drugs, SDH enzyme was inhibited by only CXM (IC50 8.10 mM).
      Interestingly, CZO activated SDH enzyme. This result was evaluated as important
      for the flow of the polyol reactions. Ki values and inhibition types were
      determined for AR. However, these values could not have determined for SDH, due
      to insufficient inhibition. CONCLUSIONS: From these results, it was concluded
      that cephalosporins may have an important effect on flow of the polyol
      metabolism.

PMID- 28758818
TI  - Genetic characterization of Bactrocera fruit flies (Diptera: Tephritidae) from
      Northeastern India based on DNA barcodes.
AB  - The Northeastern region of India, one of the mega biodiversity hot spots has
      enormous potential for the production of fruits and vegetables. Fruit flies of
      the genus Bactrocera Macquart are important pests of fruits and vegetables, and
      one of the limiting factors in successful production of these commodities. The
      relationship among some of the species is unclear due to their high molecular and
      morphological similarities. Moreover, due to the significant morphological
      resemblance between fruit fly species, reliable identification is very difficult
      task. We genetically characterized 10 fruit fly species of the genus Bactrocera
      by using standard DNA barcoding region of COI gene. The characterization and
      identification of eight species were straight forward. This study was unable to
      establish the molecular identity of Bactrocera sp. 2. Within the 547 bp region of
      partial COI gene, there were 157 variable sites of which 110 sites were parsimony
      informative, 153 were synonymous substitutions and 4 were non-synonymous
      substitutions. The estimate of genetic divergence among the ten species was in
      the range of 0-21.9% and the pairwise genetic distance of Bactrocera.
      (Bactrocera) dorsalis (Hendel) with B. (B.) carambolae was only 0.7%.
      Phylogenetic analysis formed separate clades for fruit and vegetable infesting
      fruit flies. B. (B.) aethriobasis Hardy, B. (B.) thailandica and B. (B.)
      tuberculata (Bezzi) have been reported for the first time from the Northeastern
      India. The information generated from this study would certainly have
      implications for pest management, taxonomy, quarantine and trade.

PMID- 28758819
TI  - Pharmaceutical issues during the review of European Marketing Authorisation
      Applications in Malta.
AB  - The aim of this study was to identify pharmaceutical issues encountered during
      regulatory review in European Procedures. A database of issues from Day 70
      assessment reports of 150 EU procedures was compiled; most procedures were for
      generics (108). Frequencies of common deficiencies have been calculated and
      summarised for use of all stakeholders. Out of the 150 procedures reviewed,
      covering 309 products, a total of 4796 concerns were identified. Of these
      concerns, 167 were Potential Serious Risks to Public Health, 67 were raised on
      drug substance and 100 on the drug product. The distribution of total concerns
      was as follows: 2168 concerns on drug substance and 2584 on drug product. Most
      concerns raised were on control of drug substance and drug product (834 & 626 for
      3.2.S.4 and 3.2.P.5, respectively), followed by concerns on the manufacturing
      (482 & 564 for 3.2.S.2 and 3.2.P.3, respectively) and stability 147 & 398 for
      3.2.S.7 and 3.2.P.8, respectively). In conclusion, the frequencies and trends of
      identified deficiencies together with their impact were discussed from a
      regulatory point of view. The main findings indicate that applicants would
      benefit from following published guidelines so that delays in the registration of
      medicines could be avoided.

PMID- 28758820
TI  - Antibacterial activity of human simulated epithelial lining fluid concentrations
      of amikacin inhale alone and in combination with meropenem against Acinetobacter
      baumannii.
AB  - BACKGROUND: Acinetobacter baumannii(ACBN) is a MDR organism causing pneumonia in
      ventilated patients. High MICs often result in insufficient lung exposures, thus
      poor outcomes have been observed with parenteral antimicrobials. Amikacin
      Inhale(AMK-I), is a drug-device combination of amikacin and a Pulmonary Drug
      Delivery System device. We aimed to describe the pharmacodynamic profile of human
      simulated epithelial lining fluid(ELF) exposures of AMK-I and intravenous
      meropenem alone and in combination against ACBN with variable susceptibility
      profiles. METHODS: AMK-I ELF exposures and the ELF profile of meropenem achieved
      after intravenous administration were evaluated in an in vitro pharmacodynamic
      model. Nine ACBN with amikacin/meropenem MICs of 2-512/2 to >64 mg/L were
      utilized. MICs were repeated post exposure to assess the development of
      resistance. RESULTS: AMK-I monotherapy rapidly achieved and sustained
      bactericidal activity for isolates with amikacin MIC <=128 mg/L. For isolates
      with MICs of 256 and 512 mg/L initial reductions in bacterial density were
      observed followed by regrowth. The combination produced similar bactericidal
      activity against ACBN with amikacin MICs of <=128. While the combination regimen
      produced initial reductions and prolonged the duration of activity against
      organisms with MICs of 256 and 512 mg/L, regrowth and MIC elevations were noted
      during the 72-h exposure period. CONCLUSION: The combination achieved rapid and
      sustained efficacy when amikacin MICs were <=128 mg/L and prolonged the duration
      of activity compared to monotherapy for organisms with MICs 256 mg/L and 512
      mg/L. These data support the utility of AMK-I as an adjunct for the treatment of
      pneumonia caused by A. baumannii with MICs above current susceptibility break
      points.

PMID- 28758821
TI  - Further evidence for curricular influence on student connectedness.

PMID- 28758822
TI  - The effects of individually tailored nurse navigation for patients with newly
      diagnosed breast cancer: a randomized pilot study.
AB  - AIM: Our aim was to determine the feasibility and effectiveness of an individual,
      nurse-navigator intervention for relieving distress, anxiety, depression and
      health-related quality of life in women who have been treated for breast cancer
      (BC) and are experiencing moderate-to-severe psychological and physical symptoms.
      METHODS: Fifty women with newly diagnosed BC who reported distress (score >=7 on
      distress thermometer) before surgery were included consecutively in a pilot study
      and randomized 1:1 to the intervention or the control group. The intervention
      comprised repeated screening with patient reported outcome measures and nurse
      navigation. A total of 66 women who were not distressed (score <7) were followed
      longitudinally as an observational group. Participants filled in four
      questionnaires, at baseline, after 6 months and 12 months. The primary outcome
      was psychological distress and the secondary outcomes were anxiety, depression,
      health-related quality of life and feasibility of the intervention. RESULTS:
      Women in the intervention group reported significantly greater satisfaction with
      treatment and rehabilitation and lower levels of distress (mean 2.7 vs. 5.1,
      p<.01), anxiety (mean 5.1 vs. 7.8, p = .02) and depression (mean 2.2 vs. 4.4, p =
      .04) after 12 months compared to the control group. No significant effects were
      seen on health-related quality of life. CONCLUSIONS: The study shows promising
      feasibility of the individually tailored nurse-navigation intervention and while
      no significant effects were observed after 6 months, we did find statistically
      significant effects on distress, anxiety and depression 12 months after
      diagnosis. Our results will assist in developing rehabilitation to the most
      vulnerable patients.

PMID- 28758823
TI  - Physical inactivity and platelet function in humans and brown bears: A
      comparative study.
AB  - Physical inactivity increases the risk of thromboembolism. However, good
      standardized human models on inactivity are in short supply and experimental
      models are few. Our objective was to investigate how standardized bed rest
      affects platelet aggregation in humans and to investigate if aggregation is
      altered in a translational model system - the hibernating brown bear (Ursus
      arctos). We collected blood from (1) healthy male volunteers participating in a
      21-day bed rest study in head-down tilt position (-6 degrees ) 24 h a day; (2)
      free-ranging brown bears captured during winter hibernation and again during
      active state in summer. We analyzed platelet function using multiple electrode
      platelet aggregometry. In total, 9 healthy male volunteers (age 31.0 +/- 6.4
      years) and 13 brown bears (7 females and 6 males, age 2.8 +/- 0.6 years) were
      included. In hibernating bears adenosine diphosphate, arachidonic acid, thrombin
      receptor activating peptide, and collagen impedance aggregometry tests were all
      halved compared to summer active state. In human volunteers no statistically
      significant changes were found between baseline and the end of bed rest. In human
      male volunteers 3 weeks of bed rest did not affect platelet function. In
      hibernating brown bears platelet aggregation was halved compared to summer and we
      hypothesize that this is a protective measure to avoid formation of thrombi under
      periods of low blood flow.

PMID- 28758824
TI  - Vaccine development and trials in low and lower-middle income countries: Key
      issues, advances and future opportunities.
AB  - Over the past 10 years there has been an increase in the number of vaccine
      clinical studies conducted in resource limited countries. These include vaccine
      trials for diseases such as malaria and dengue fever which are endemic to many
      low and lower-middle income countries. Concurrent with the increase in the number
      of trials, has been the increase and improvement in local infrastructure to
      enable the appropriate conduct and oversight of trials in these settings,
      including strengthening of local scientific capabilities, ethical and regulatory
      oversight. While significant advances have been made, there remain gaps to be
      addressed including strengthening pharmacovigilance in these regions. There are
      also opportunities to establish novel collaborations to address diseases specific
      to these populations including strengthening local manufacturers, new ways to
      engage established large pharmaceutical companies and leveraging established
      global infrastructure and pathways to develop innovative products beyond
      vaccines.

PMID- 28758825
TI  - Rationale for targeting tumor cells in their microenvironment for mantle cell
      lymphoma treatment.
AB  - Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma associated with
      poor prognosis, and despite recent improvements in the therapeutic strategies for
      treating MCL, its management remains challenging. While improvements in next
      generation sequencing technology have greatly increased our understanding of the
      intrinsic abnormalities of MCL, the role of extrinsic signaling remains largely
      unknown. Recent studies have highlighted the central role of the MCL
      microenvironment in tumor cell survival, drug resistance and proliferation.
      Characterization of the diverse MCL tumoral niches and comprehension of the
      crosstalk between tumor cells and surrounding cells within the MCL
      microenvironment are needed to increase treatment efficacy. Here, we reviewed the
      recent findings regarding the MCL microenvironment that could be rapidly
      translated into new therapeutic strategies to overcome drug resistance during MCL
      treatment.

PMID- 28758826
TI  - Implication of sphingosine-1-phosphate signaling in diseases: molecular mechanism
      and therapeutic strategies.
AB  - Sphingosine-1-phosphate signaling is emerging as a critical regulator of cellular
      processes that is initiated by the intracellular production of bioactive lipid
      molecule, sphingosine-1-phosphate. Binding of sphingosine-1-phosphate to its
      extracellular receptors activates diverse downstream signaling that play a
      critical role in governing physiological processes. Increasing evidence suggests
      that this signaling pathway often gets impaired during pathophysiological and
      diseased conditions and hence manipulation of this signaling pathway may be
      beneficial in providing treatment. In this review, we summarized the recent
      findings of S1P signaling pathway and the versatile role of the participating
      candidates in context with several disease conditions. Finally, we discussed its
      possible role as a novel drug target in different diseases.

PMID- 28758827
TI  - Lymphoproliferative disorders in patients with rheumatoid arthritis in the era of
      widespread use of methotrexate: A review of the literature and current
      perspective.
AB  - Lymphoproliferative disorders (LPD) in patients receiving methotrexate (MTX) have
      gained strong attention. In this article, I reviewed the basic and clinical
      findings of this issue. Patients with RA possess a high risk of lymphoma, but
      epidemiological evidence showing an association between the use of MTX and
      lymphoma is still limited. Rapid regression of LPD after stopping MTX in patients
      with RA strongly suggests that there is a causative relationship. Genetic
      predisposition, accumulated inflammation, impaired generation of Epstein-Barr
      virus (EBV)-specific cytotoxic T lymphocytes, effects of MTX on the regulation of
      EBV genes, and low hypermethylation of apoptosis-related genes are relevant to
      the development of LPD and rapid regression after cessation of MTX. The clinical
      and histological characteristics of LPD in RA patients who are treated with MTX
      have been established, and recent data indicate that initial cessation of MTX and
      watchful waiting to observe an increase in peripheral lymphocyte counts have a
      therapeutic value. In advanced cases, various chemotherapy regimens are used, and
      consultation with hematologists is recommended to select the optimal treatment.
      There is no consensus on the treatment of RA after development of LPD, and long
      term observation is necessary to investigate the safety of disease-modifying
      antirheumatic drugs in these patients.

PMID- 28758828
TI  - Second trimester extracellular microRNAs in maternal blood and fetal growth: An
      exploratory study.
AB  - Healthy feto-maternal communication is critical during pregnancy and is
      orchestrated by the placenta. Dysfunction of the placenta leads to fetal growth
      complications; however, the underlying biological mechanisms have yet to be fully
      elucidated. Circulating extracellular microRNAs (exmiRNAs) in the blood have been
      implicated in cell-to-cell communication. Therefore, exmiRNAs may provide useful
      biological information about communication between the mother, the fetus, and the
      placenta during pregnancy. We used logistic regression to determine the
      association of exmiRNAs with abnormal fetal growth by comparing mothers of
      infants classified as small-for-gestational age (SGA) (n = 36) and large-for
      gestational age (LGA) (n = 13) to appropriate-for-gestational age (AGA), matched
      by gestational age at delivery and infant sex. In addition, we used linear
      regression to determine associations between exmiRNAs and birth weight-for
      gestational age (BWGA) z-score (n = 100), adjusting for maternal age, body mass
      index, and parity. We found that higher levels of miR-20b-5p, miR-942-5p, miR-324
      3p, miR-223-5p, and miR-127-3p in maternal serum were associated with lower odds
      for having a SGA vs. AGA infant, and higher levels of miR-661, miR-212-3p, and
      miR-197-3p were associated with higher odds for having a LGA vs. AGA infant. We
      also found associations between miR-483-5p, miR-10a-5p, miR-204-5p, miR-202-3p,
      miR-345-5p, miR-885-5p, miR-127-3p, miR-148b-3p, miR-324-3p, miR-1290, miR-597
      5p, miR-139-5p, miR-215-5p, and miR-99b-5p and BWGA z-score. We also found sex
      specific associations with exmiRNAs and fetal growth. Our findings suggest that
      exmiRNAs circulating in maternal blood at second trimester are associated with
      fetal growth. Validation of our findings may lead to the development of minimally
      invasive biomarkers of fetal growth during pregnancy.

PMID- 28758829
TI  - Measurement of lipid transfer proteins in genetically engineered maize using
      liquid chromatography with tandem mass spectrometry (LC-MS/MS).
AB  - Endogenous allergenicity evaluation is a required part of the risk assessment for
      genetically engineered (GE) crops. Although maize is not considered a major
      allergenic food, a lipid transfer protein (Zea m 14) in maize grain has been
      identified as a potential IgE-mediated food allergen. Currently, the relationship
      between allergen exposure and risk of sensitization is not well understood.
      Hence, reliable quantitative methods are useful for determining the natural range
      and variability of allergen levels across multiple geographies and genetic
      backgrounds. A LC-MS/MS analytical method was developed and validated in our
      laboratory to quantify Zea m 14 in grain from 2 GE maize hybrids and 20 non-GE
      maize hybrids. The measured Zea m 14 levels in GE maize grain and conventional
      non-GE maize grain ranged from 146.87 to 574.93 ng/mg across 16 field sites
      located in the United States and Argentina. The method accurately quantified
      endogenous Zea m 14 from maize grain and results show Zea m 14 levels in the GE
      maize varieties were within the natural variation observed in traditionally bred
      non-GE maize.

PMID- 28758830
TI  - The truth lies somewhere in the middle: Swinging between globalization and
      regionalization of medical education in Japan.
AB  - Japan is well known as a super-aging society, with a low birth rate, and has been
      ranked as one of the countries having the highest quality of healthcare system.
      Japan's society is currently approaching a major turning point with regard to
      societal and healthcare reforms, which are influenced by international trends and
      regional needs. Development of Japanese healthcare human resources, including
      medical students, is now expected to ride the wave of globalization, while
      resolving regional problems in the training and delivery of healthcare. Terms and
      global trends in medical education, such as outcome-based education, community
      based education, reflective learning, international accreditation of medical
      education, and professionalization of educators are well translated into the
      Japanese language and embraced positively among the Japanese medical educators.
      However, these trends occasionally sit uncomfortably with cultural variations
      that are often a common approach in Japan; notably, "hansei" (introspection) and
      "kaizen" (change for the better). In the world facing a new era where people are
      unsettled between globalism and regionalism, Japan's future mission is to steer a
      balanced route that recognizes both global and regional influences and produce
      global health professionals educators.

PMID- 28758831
TI  - TET1 deficiency attenuates the DNA damage response and promotes resistance to DNA
      damaging agents.
AB  - Recent studies have shown that loss of TET1 may play a significant role in the
      formation of tumors. Because genomic instability is a hallmark of cancer, we
      examined the potential involvement of 10-11 translocation 1 (TET1) in the DNA
      damage response (DDR). Here we demonstrate that, in response to clinically
      relevant doses of ionizing radiation (IR), human glial cells made TET1-deficient
      with lentiviral vectors displayed greater numbers of colony forming units and
      lower levels of apoptotic markers compared with glial cells transduced with
      control vectors; yet, they harbored greater DNA strand breaks. The G2/M check
      point and expression of cyclin B1 were greatly diminished in TET1-deficient
      cells, and TET1-deficient cells displayed lower levels of gammaH2A.x following
      exposure to IR. Levels of DNA-PKcs, which are DNA-PK complex members, were lower
      in TET1-deficient cells compared with control cell lines. However, levels of ATM
      were similar in both cell lines. Cyclin B1, DNA-PKcs, and gammaH2A.x levels were
      each rescued by reintroduction of the TET1 catalytic domain. Finally, cytosine
      methylation within intron 1 of PRKDC, the gene encoding DNA-PKcs, was
      significantly higher upon depletion of TET1. Taken together, this study
      illustrates the involvement of TET1 in the different arms of the DDR and suggests
      its loss results in the continued survival of cells with genomic instability.

PMID- 28758832
TI  - Functional regulation of plant NADPH oxidase and its role in signaling.
AB  - Reactive oxygen species (ROS) serve as a key signal messenger in plant cells.
      Plant NADPH oxidases, known as respiratory burst oxidase homologues (RBOHs),
      catalyze the production of superoxide, a type of ROS, and are involved in several
      essential processes in plants. In this review, we discuss recent studies about
      functional regulation of RBOHs by calcineurin B-like protein (CBL)-CIPKs (the CBL
      interacting protein kinases), small GTPases, and lipids that integrate
      developmental cues and external stimuli.

PMID- 28758833
TI  - Differentially localized rice ethylene receptors OsERS1 and OsETR2 and their
      potential role during submergence.
AB  - Ethylene is gaseous plant hormone that controls a variety of physiologic
      activities. OsERS1 and OsETR2 are major ethylene receptors in rice that have been
      reported to have different regulatory functions. The GFP fused N-terminus of
      OsERS1 and OsETR2 showed differentially localization patterns when transiently
      expressed in onion epidermal cells. Base on these results, we suggested that
      OsERS1 could be localized to plasma membranes, whereas OsETR2 could be localized
      to the endoplasmic reticulum. Furthermore, instead of the constitutive expression
      profile of OsERS1, OsETR2 is differentially expressed in seedlings of light/dark
      grown conditions, submergence or exogenous ethylene treatments. Our results and
      others support the notion that OsERS1 and OsETR2 could have different roles
      during rice plant submergence.

PMID- 28758835
TI  - Kinematics and metabolic cost of running on an irregular treadmill surface.
AB  - The purpose of this study was to investigate the kinematic and metabolic effects
      of running on an irregular surface. We also examined how altering the frontal
      plane foot angle (inversion/eversion) at contact using real-time visual feedback
      would affect these other variables. Sixteen participants completed three running
      bouts lasting 5-7 minutes each on an irregular surface (IS) treadmill, a
      traditional smooth surface (SS) treadmill, and on SS while receiving visual
      feedback of the frontal plane foot angle at contact (SSF) with a goal of matching
      IS foot angle on SS. Frontal plane foot angle increased 40% from IS to SS (IS:
      8.4 +/- 4.09 degrees , SS: 11.8 +/- 4.52 degrees , P < 0.0001, ES 1.40). Knee
      flexion angle at contact decreased 33% from IS to SS (IS: 9.2 +/- 4.88 degrees ,
      SS: 6.2 +/- 5.03 degrees , P < 0.0001, ES 1.30). Rate of oxygen consumption
      decreased by 10% from IS to SS (IS: 37.9 +/- 5.68 ml.kg-1.min-1, SS: 34.1 +/-
      5.07 ml.kg-1.min-1, P < 0.0001, ES 3.05). PSD of leg accelerations decreased by
      38% (IS: 0.17 +/- 0.07 g2/Hz, SS: 0.106 +/- 0.05 g2/Hz, P < 0.000, ES 1.69).
      Frontal plane foot angle decreased by 14% from SS to SSF (SS: 11.8 +/- 4.52
      degrees , SSF: 10.1 +/- 4.42 degrees , P = 0.027. ES 0.62) but did not result in
      significant changes in any other variables. There were no significant differences
      in shock attenuation between any conditions (IS: -9.8 +/- 2.26 dB, SS: -9.5 +/-
      3.12 dB, SSF: -9.9 +/- 2.62 dB, P = 0.671). Running with greater eversion on the
      irregular surface may be an attempt by runners to reduce the perceived potential
      of an inversion ankle sprain. As a partial compensation for the decreased foot
      angle, runners increased knee flexion. This maintained shock attenuation but
      increased the rate of oxygen consumption. Altering the foot angle at contact
      using feedback on the SS caused the knee angle at contact to increase, but did
      not change shock attenuation or metabolic cost.

PMID- 28758834
TI  - Preferential interactions of trehalose, L-arginine.HCl and sodium chloride with
      therapeutically relevant IgG1 monoclonal antibodies.
AB  - Preferential interactions of weakly interacting formulation excipients govern
      their effect on the equilibrium and kinetics of several reactions of protein
      molecules in solution. Using vapor pressure osmometry, we characterized the
      preferential interactions of commonly used excipients trehalose, L-arginine.HCl
      and NaCl with three therapeutically-relevant, IgG1 monoclonal antibodies that
      have similar size and shape, but differ in their surface hydrophobicity and net
      charge. We further characterized the effect of these excipients on the reversible
      self-association, aggregation and viscosity behavior of these antibody molecules.
      We report that trehalose, L-arginine.HCl and NaCl are all excluded from the
      surface of the three IgG1 monoclonal antibodies, and that the exclusion behavior
      is linearly related to the excipient molality in the case of trehalose and NaCl,
      whereas a non-linear behavior is observed for L-arginine.HCl. Interestingly, we
      find that the magnitude of trehalose exclusion depends upon the nature of the
      protein surface. Such behavior is not observed in case of NaCl and L-arginine.HCl
      as they are excluded to the same extent from the surface of all three antibody
      molecules tested in this study. Analysis of data presented in this study provides
      further insight into the mechanisms governing excipient-mediated stabilization of
      mAb formulations.

PMID- 28758836
TI  - Contributions for classification of platelet rich plasma - proposal of a new
      classification: MARSPILL.
AB  - Platelet-rich plasma (PRP) has emerged as a significant therapy used in medical
      conditions with heterogeneous results. There are some important classifications
      to try to standardize the PRP procedure. The aim of this report is to describe
      PRP contents studying celular and molecular components, and also propose a new
      classification for PRP. The main focus is on mononuclear cells, which comprise
      progenitor cells and monocytes. In addition, there are important variables
      related to PRP application incorporated in this study, which are the harvest
      method, activation, red blood cells, number of spins, image guidance, leukocytes
      number and light activation. The other focus is the discussion about progenitor
      cells presence on peripherial blood which are interesting due to
      neovasculogenesis and proliferation. The function of monocytes (in tissue
      macrophages) are discussed here and also its plasticity, a potential property for
      regenerative medicine treatments.

PMID- 28758837
TI  - Epoxy resin as a new alternative sorbent phase for stir bar sorptive extraction
      for the determination of triclosan and methyl-triclosan.
AB  - The main objective of this study is to propose a new sorbent phase based on a
      commercial epoxy resin, for use as an alternative sorbent in the stir bar
      sorptive extraction (SBSE) technique. The analytes triclosan (TCS) and methyl
      triclosan (MTCS) were selected in order to demonstrate the application of the
      bars, using some water samples as matrices. The extraction conditions of sample
      volume, stirring time, pH, temperature and ionic strength were evaluated, and for
      the back extraction, the bars were sonicated using 1.00 mL of acetonitrile for 10
      min. The technique of liquid chromatography using a diode array detector was
      employed for the quantitation. Analytical curves of between 2.50 and 50.0 MUg L-1
      with r2 of 0.9894 (TCS) and 0.9933 (MTCS), and limit of detection (LOD) values of
      0.6 MUg L-1 (TCS) and 2.0 MUg L-1 (MTCS) were observed. Recovery values between
      100.4% and 121.6% were verified for ultrapure water and between 50.3% and 93.8%
      for wastewater samples, thereby suggesting the possibility of employing the bars
      for quantitation of TCS and MTCS in aqueous samples. This is the first time that
      this resin has been applied without the need for the adhesion of any additional
      sorbent phase, thereby providing a simple and low-cost method. Another feature is
      that only eight bars were employed in the entire work, and each bar was used
      approximately 40 times with the same performance without memory effects.

PMID- 28758838
TI  - The Effect of a Supreme Court Decision Regarding Gay Marriage on Social Norms and
      Personal Attitudes.
AB  - We propose that institutions such as the U.S. Supreme Court can lead individuals
      to update their perceptions of social norms, in contrast to the mixed evidence on
      whether institutions shape individuals' personal opinions. We studied reactions
      to the June 2015 U.S. Supreme Court ruling in favor of same-sex marriage. In a
      controlled experimental setting, we found that a favorable ruling, when presented
      as likely, shifted perceived norms and personal attitudes toward increased
      support for gay marriage and gay people. Next, a five-wave longitudinal time
      series study using a sample of 1,063 people found an increase in perceived social
      norms supporting gay marriage after the ruling but no change in personal
      attitudes. This pattern was replicated in a separate between-subjects data set.
      These findings provide the first experimental evidence that an institutional
      decision can change perceptions of social norms, which have been shown to guide
      behavior, even when individual opinions are unchanged.

PMID- 28758839
TI  - Is there a transgenerational inheritance of host resistance against pathogens?
      Lessons from the Galleria mellonella-Bacillus thuringiensis interaction model.

PMID- 28758840
TI  - 'I'd rather die happy': residents' experiences with food regulations, risk and
      food choice in residential aged care. A qualitative study.
AB  - BACKGROUND: Food regulations exist to protect older people in residential aged
      care, leading to the restriction of potentially hazardous foods. The impacts of
      malnutrition, resident centred care and the importance of maintaining individual
      autonomy for older people are well documented. By contrast, there is scant
      literature describing residents' perceptions of food regulations and food risks
      in the residential aged care setting. AIMS: The aim of this study is to explore
      resident perceptions of food choice and food restrictions in residential aged
      care. METHODS: Using a qualitative, hermeneutic phenomenological design, semi
      structured interviews were conducted with six participants recruited from two
      residential aged care facilities. Interviews were audio-taped, transcribed
      verbatim and thematically analysed. RESULTS: The following key themes emerged in
      this study: participants were largely unaware of food regulations and risks, yet
      expressed the desire to make their own choices. Participants provided
      contradictory accounts of their experiences with food in residential aged care,
      which emphasises the ongoing challenge of meeting individual preferences.
      CONCLUSION: These themes warrant further investigation, particularly in relation
      to the impact of food regulations on food choice and the meaning of risk to older
      people in residential aged care. This research provides new insight into the
      perceptions of residents regarding their individual autonomy and independence
      against legislated risk minimization strategies. Impact statement This article
      raises the issue of risk taking and food choices from the perspective of
      residents in a residential aged care facility.

PMID- 28758841
TI  - Associations between handedness and executive function in upper-middle-aged
      people.
AB  - Many studies have investigated the relationship between handedness and executive
      functioning using behavioural measures, although the exact nature of this
      relationship remains unclear. In this study, the relationship between handedness
      and executive function was examined using the D-CAT (Digit Cancellation Test)
      performances of 76 left-handed (42 men and 34 women) and 76 age-matched right
      handed (42 men and 34 women) healthy community dwellers. The mean age of the
      participants was 62.7 years (SD = 10.3). In addition, the visuospatial
      performance was also examined using the Money Road Test. Left-handed people of
      both sexes showed a poor performance on both tests than right-handed people.
      Right-handed people showed typical laterality with regard to the relationship
      between the sex and facets of cognition, whereas left-handed people showed no
      clear laterality difference. Men showed no handedness difference in the executive
      function and women showed no handedness difference in the case of the
      visuospatial function test. The possible contributions of the three different
      executive functioning components, information updating, shifting, and inhibition,
      to this handedness difference in the upper-middle-aged people, are discussed.

PMID- 28758842
TI  - Copper wastewater treatment with high concentration in a two-stage
      crystallization-based combined process.
AB  - Crystallization process in a fluidized bed reactor (FBR) to treat metal
      wastewaters has been considered as a suitable alternative to the chemical
      precipitation. However, the process efficiency was high under low initial
      concentrations, but decreased with the increase of metal concentration due to the
      unwanted homogeneous precipitation. Aiming at the treatment of heavy metal
      wastewater with high concentration, a modified FBR (mFBR) was investigated and
      the two-stage crystallization-based combined process was proposed. mFBR was more
      suitable for copper removal with high concentration than FBR. The copper
      concentration was reduced to 9.92 mg/L after the two-stage crystallization,
      corresponding to the removal rate of 96.6%. After filtration and ion exchange,
      the copper concentration was further reduced to 0.739 and 0.175 mg/L. During
      crystallization precipitation, the median size of the silica sand was gradually
      increased from 0.182 to 0.260 mm. The glossy surface of silica was gradually
      densely covered with short crystal precipitate, and obvious angularity gradually
      disappeared due to the deposition of copper precipitate. In addition, the water
      content of the crystallization precipitate was about 13.7% and much lower than
      the traditional chemical sludge. Copper precipitate was mainly composed of CuCO3
      and Cu(OH)2.

PMID- 28758843
TI  - Railway safety climate: a study on organizational development.
AB  - The safety climate of an organization is considered a leading indicator of
      potential risk for railway organizations. This study adopts the perceptual
      measurement-individual attribute approach to investigate the safety climate of a
      railway organization. The railway safety climate attributes are evaluated from
      the perspective of railway system staff. We identify four safety climate
      dimensions from exploratory factor analysis, namely safety communication, safety
      training, safety management and subjectively evaluated safety performance.
      Analytical results indicate that the safety climate differs at vertical and
      horizontal organizational levels. This study contributes to the literature by
      providing empirical evidence of the multilevel safety climate in a railway
      organization, presents possible causes of the differences under various cultural
      contexts and differentiates between safety climate scales for diverse workgroups
      within the railway organization. This information can be used to improve the
      safety sustainability of railway organizations and to conduct safety supervisions
      for the government.

PMID- 28758844
TI  - Screening of the structural, topological, and electronic properties of the
      functionalized Graphene nanosheets as potential Tegafur anticancer drug carriers
      using DFT method.
AB  - In the present work, we apply comprehensive theoretical calculations in order to
      study Tegafur drug adsorption on the nanostructured functionalized Graphene with
      hydroxyl, epoxide, carbonyl, and carboxyl groups in the water environment. The
      physical nature of Tegafur adsorption offers advantages in terms of easy
      desorption of anticancer molecule with no structural or electronic change of the
      adsorbed drug. By functionalization of Graphene nanosheet with a carbonyl group,
      a considerable increase on the binding energy between Tegafur drug and the
      nanosheet is noted. Diminish in energy gap with the adsorption of Tegafur drug on
      the functionalized nanosheets shows that the reactivity of functionalized
      complexes increases upon loading of the drug molecule. Besides, the adsorption
      process yields an increase of the polarity which causes the possibility of the
      solubility and dispersion of the considered complexes enhances. This result is
      indicative the suitability of the nanomaterials toward Tegafur drug delivery
      within the biological environments. The high solvation energy of Tegafur
      anticancer drug adsorbed functionalized Graphene models enforced their
      applicability as nanocarriers in the living system. These results are extremely
      relevant that the chemical modification of Graphene nanosheet using covalent
      functionalization scheme is an effectual approach for loading and delivery of
      Tegafur drug molecule within biological systems.

PMID- 28758845
TI  - Diloxanide furoate binary complexes with beta-, methyl-beta-, and hydroxypropyl
      beta-cyclodextrins: inclusion mode, characterization in solution and in solid
      state and in vitro dissolution studies.
AB  - The purpose of this study was to investigate the effect on solubility and
      dissolution rate of binary complexes of beta-(betaCD), methyl-(MbetaCD) and
      hydroxypropyl-beta-cyclodextrin (HPbetaCD) with diloxanide furoate (DF). The
      complexation in solution was evaluated by phase solubility studies and 1H nuclear
      magnetic resonance (NMR). Enhanced water solubility of DF was obtained with the
      DF:MbetaCD system (61-fold). The mode of inclusion was supported by NMR
      experiments, which indicated that real inclusion complexes were formed between DF
      and MbetaCD or HPbetaCD. Solid state analysis was performed using infrared and
      thermal methods, which suggested the formation of true inclusion complexes of DF
      with two derivatized cyclodextrins, MbetaCD and HPbetaCD, and an exclusion
      complex with betaCD when the systems were prepared by freeze-dried technique.
      Dissolution studies conducted in simulated gastric fluid (2 h) and subsequent
      simulated intestinal fluid (next 4 h) showed increased dissolution rate of DF
      from the freeze-dried systems with betaCD, MbetaCD, and HPbetaCD (85; 77 and 75%
      of dissolved drug at 5 min, respectively) and 100% of the drug dissolved at 150
      min for the three systems. The enhancement of the solubility and the dissolution
      of DF observed make these complexes promising candidates for the preparation of
      oral pharmaceutical formulations.

PMID- 28758846
TI  - Efficacy of parecoxib sodium on postoperative shivering: meta-analysis of
      clinical trials.
AB  - Objective To evaluate the effect of parecoxib on preventing postoperative
      shivering. Methods Main outcomes were the relative risk (odds ratio, OR) and 95%
      confidence interval (CI) relative to the incidence of shivering. Results Fourteen
      trials with 1,175 patients were analyzed. The pooled evidence suggested that
      parecoxib sodium, given before anesthesia or postoperatively (only 4 cases), had
      the potential to prevent postoperative shivering (OR = 0.21, 95% CI, 0.16, 0.29).
      Compared with the placebo, parecoxib sodium significantly lowered the incidence
      of postoperative shivering as follows: mild shivering [OR = 0.51, 95% CI (0.35,
      0.74)]; moderate shivering [OR = 0.28, 95% CI (0.18, 0.45)]; severe shivering [OR
      = 0.18, 95% CI (0.10, 0.33)]. Compared with placebo, there was no significant
      association of parecoxib sodium with restlessness [OR = 0.95, 95% CI (0.59,
      1.52)] or nausea/vomiting [OR = 0.24, 95% CI (0.09, 0.66)]. In addition,
      pethidine rescue was used significantly more often in the control group than in
      the parecoxib sodium group [OR = 0.22, 95% CI (0.09, 0.53)]. Conclusions
      Parecoxib sodium may be an effective strategy for preventing postoperative
      shivering.

PMID- 28758847
TI  - Sex-related differences in bronchial parameters and pulmonary function test
      results in patients with chronic obstructive pulmonary disease based on three
      dimensional quantitative computed tomography.
AB  - Objective This study was performed to evaluate the effect of sex on bronchial
      parameters and the predicted forced expiratory volume in 1 s expressed as a
      percentage of the forced vital capacity (FEV1% pred) on pulmonary function
      testing. Methods The data of 359 patients with chronic obstructive pulmonary
      disease (COPD) with available FEV1% pred and computed tomography (CT) images were
      retrospectively reviewed. FACT-Digital lung TM software (DeXin, Xi'an, China) was
      used to perform fully automated three-dimensional CT quantitative measurements of
      the bronchi. Generation 5 to 7 bronchi were measured, and the parameters analyzed
      were the lumen diameter (LD), wall thickness (WT), lumen area (LA), and WA% [WA /
      (WA + LA) * 100%]. Results In the smoking, smoking cessation, and nonsmoking
      groups, women had a significantly larger WA% and smaller LD, WT, and LA than men.
      The FEV1% pred was significantly lower in women than men in the smoking and
      smoking cessation groups. The FEV1% pred was significantly higher in women than
      men in the nonsmoking group. Conclusion Sex-related differences may partially
      explain why smoking women experience more severe pulmonary function impairment
      than men among patients with COPD.

PMID- 28758848
TI  - Double-plating fixation of comminuted femoral shaft fractures with concomitant
      thoracic trauma.
AB  - Objective This study was performed to evaluate the clinical outcomes in adult
      polytraumatized patients with thoracic injury and femoral shaft fractures treated
      with double-plating fixation. Methods From November 2010 to October 2014, 15
      polytraumatized patients with femoral shaft fractures were enrolled in this
      retrospective study. Radiographic findings and functional outcomes were assessed
      at 1, 3, 6, and 12 months postoperatively. Results Fourteen (93%) of the 15
      femoral shaft fractures achieved bony union, with a mean time to union of 9.2
      months. The mean Nonarthritic Hip Score and Lysholm Knee Score was 89.4 and 87.2
      points, respectively. The range of motion of the knee joint was comparable
      between the injured and uninjured legs (116 degrees  and 121 degrees ,
      respectively). Conclusions Our findings suggest that lower limb function returns
      to normal after orthogonal double-plating fixation, which is an alternative
      technique to intramedullary nailing for femoral diaphyseal fractures in patients
      with severe chest injury.

PMID- 28758849
TI  - Clinical profile of unclassifiable interstitial lung disease: Comparison with
      chronic fibrosing idiopathic interstitial pneumonias.
AB  - Objective Unclassifiable interstitial lung disease (ILD) is a common problem in
      clinical practice. These patients pose a distinct challenge with regard to
      appropriate evaluation and management. We investigated the clinical features and
      prognosis of unclassifiable ILD and compared its clinical profile with that of
      idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial
      pneumonia (NSIP). Methods Patients with IPF (n = 40), NSIP (n = 14), and
      unclassifiable ILD (n = 27) were selected from an ongoing database. Baseline
      clinical features, pulmonary function, and the extent of fibrosis on high
      resolution computed tomography (HRCT) were evaluated. Mortality was estimated
      based on the ILD-Gender, Age, Physiology (ILD-GAP) index and composite
      physiologic index (CPI). Results IPF was associated with the worst survival
      (hazard ratio [HR] = 4.361 compared with NSIP), followed by unclassifiable cases
      (HR = 1.251 compared with NSIP). Increasing mortality was significantly impacted
      by age (HR = 1.04 per 1-year increase), lower carbon monoxide diffusing capacity
      of the lung (HR = 0.97), HRCT interstitial score (HR = 1.119 per 1-point
      increase), ILD-GAP score (HR = 1.570 per 1-point increase), and CPI (HR = 1.039
      per 1-point increase). Conclusions Patients with unclassifiable ILD had an
      intermediate prognosis between that of IPF and NSIP. Patients at high risk of
      mortality can be identified using baseline clinical, physiological, and
      radiological features.

PMID- 28758850
TI  - A picture-based carbohydrate-counting resource for Somalis.
AB  - Objective Carbohydrate counting is essential for effective management of type 1
      diabetes (T1D). Somali diet-specific carbohydrate-counting references are
      lacking, creating an additional barrier to effective diabetes control. We
      developed a picture-based carbohydrate-counting resource for Somalis with T1D.
      Methods Traditional Somali foods were selected using a variety of methods.
      Serving sizes and carbohydrate calculations were tabulated using the United
      States Department of Agriculture National Nutrient Database for Standard
      Reference. Carbohydrate contents of home-prepared foods were calculated by
      measuring the total yield and total carbohydrates of ingredients in the recipe
      divided by the number of servings to be consumed. When available, recipes were
      used for food preparation and analysis for more accurate carbohydrate estimation.
      Results Photographs of prepared Somali foods were compiled into a PDF file. While
      introductions are written in text, the resource is primarily picture-based to
      bypass limited literacy. The resource is shared free of charge via the following
      link: http://journals.sagepub.com/doi/suppl/10.1177/0300060517718732 . The link
      will be updated annually with new information. Conclusion There is a necessity to
      tailor educational materials to address the needs of Somalis with diabetes. We
      have created a picture-based nutrition resource for carbohydrate counting of
      traditional Somali foods and have made this freely available to individuals
      worldwide.

PMID- 28758851
TI  - Effects of aqueous extract of Arctium lappa L. roots on serum lipid metabolism.
AB  - Objective To identify potential genes that may be involved in lipid metabolism in
      rats after treatment with aqueous extract of Arctium lappa L (burdock). Methods
      Rats were randomly divided into six groups: (i) control (standard diet); (ii)
      model group (high-fat diet only); (iii) high-fat diet and low-dose aqueous
      burdock root extract (2 g/kg); (iv) high-fat diet and moderate-dose aqueous
      burdock root extract (4 g/kg); (v) high-fat diet and high-dose aqueous burdock
      root extract (8 g/kg); and (vi) a positive control group exposed to a high-fat
      diet and simvastatin (10 mg/kg). Kyoto Encyclopedia of Genes and Genomes (KEGG)
      analysis was performed to find the potential candidate genes involved in the
      modulation of blood lipids by treatment with aqueous burdock root extract.
      Results Burdock root extract reduced body weight and cholesterol levels in rats.
      KEGG analysis revealed 113 genes that were involved in metabolic pathways. Of
      these, 27 potential genes associated with blood lipid metabolism were identified.
      Conclusions Aqueous extract of burdock root reduced body weight and cholesterol
      in rats, possibly by modulating the differential expression of genes.

PMID- 28758852
TI  - Dehydroepiandrosterone supplementation in women undergoing assisted reproductive
      technology with poor ovarian response. A prospective case-control study.
AB  - Objective The effects of dehydroepiandrosterone (DHEA) supplementation in Saudi
      Arabian women with poor ovarian response (POR) is presently unknown. The present
      study aimed to assess the benefits of DHEA supplementation in women undergoing in
      vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Methods
      This was a prospective case-control study involving 62 women who were diagnosed
      with POR and underwent IVF/ICSI between January 2012 and June 2016. The positive
      influence of DHEA in 34 women, compared with 28 women without supplementation,
      was defined as improvements in the number of oocytes retrieved, the fertilization
      rate, the number of grade I embryos generated and the pregnancy rate. Results
      Both groups were evenly matched for age, body mass index and laboratory test
      parameters. There were statistically significant differences between the groups
      with and without DHEA supplementation for oocyte yield (6.35 +/- 2.41 versus 3.98
      +/- 3.2), Grade I embryos generated (55% versus 30%), positive pregnancy rate
      (21/34 versus 10/28), and live birth rate (18/34 versus 4/28). Conclusion DHEA
      supplementation in women with POR had a positive effect on hormonal profiles, the
      quality of the endometrium, the number of oocytes retrieved, the quality of
      embryos, and the pregnancy and live birth rates.

PMID- 28758853
TI  - One-year clinical outcomes of patients implanted with a Resolute OnyxTM
      zotarolimus-eluting stent.
AB  - Objective To evaluate the 1-year clinical outcomes of patients who received the
      Resolute OnyxTM stent. Methods This was a single-centre, retrospective registry
      analysis that reviewed the clinical data from all patients who were implanted
      with a Resolute OnyxTM stent between March 2015 and February 2016. Clinical
      follow-up was performed at 1 year post-implantation. Results A total of 252
      patients received a Resolute OnyxTM stent and two patients were lost to follow
      up. The mean age of the cohort was 66.9 years and 113 (45.2%) had diabetes
      mellitus. Thirty-eight patients (15.2%) had left main disease and 73 (29.2%) had
      three-vessel disease. A total of 175 patients (70.0%) had small vessel disease
      (<2.75 mm) and 210 (84.0%) had long lesions (>20 mm). The 1-year target lesion
      failure was 4.4% (11 of 250), cardiovascular death occurred in eight patients
      (3.2%), ischaemia-driven target lesion revascularization was undertaken in five
      patients (2.0%) and stent thrombosis occurred in one patient (0.4%). Conclusion
      The Resolute OnyxTM stent showed a favourable 1-year clinical performance in a
      real-world population.

PMID- 28758854
TI  - 3D-QSAR pharmacophore-based virtual screening, molecular docking and molecular
      dynamics simulation toward identifying lead compounds for NS2B-NS3 protease
      inhibitors.
AB  - NS2B-NS3 protease has been identified to serve as lead drug design target due to
      its significant role in West Nile viral (WNV) and dengue virus (DENV)
      reproduction and replication. There are currently no approved chemotherapeutic
      drugs and effective vaccines to inhibit DENV and WNV infections. In this work, 3D
      QSAR pharmacophore model has been developed to discover potential inhibitory
      candidates. Validation through Fischer's model and decoy test indicate that the
      developed 3D pharmacophore model is highly predictive for DENV inhibitors, which
      was then employed to screen ZINC chemical library to obtain reasonable hits.
      Following ADMET filtering, 15 hits were subjected to further filter through
      molecular docking and CoMFA modeling. Finally, top three hits were identified as
      lead compounds or potential inhibitory candidates with IC50 values of ~0.4637 uM
      and fitness of ~57.73. It is implied from CoMFA modeling that substituents at the
      side site of benzotriazole such as a p-nitro group (e.g. biphenyl head) and a
      carbonyl (e.g. carboxylate function) at the side site of furan or amino group may
      improve bioactivity of ZINC85645245, respectively. Molecular dynamics simulations
      (MDS) were performed to discover new interactions and reinforce the binding modes
      from docking for the hits also. The QSAR and MDS results obtained from this work
      should be useful in determining structural requirements for inhibitor development
      as well as in designing more potential inhibitors for NS2B-NS3 protease.

PMID- 28758855
TI  - Targeting DNA hypermethylation: Computational modeling of DNA demethylation
      treatment of acute myeloid leukemia.
AB  - In acute myeloid leukemia (AML) DNA hypermethylation of gene promoters is
      frequently observed and often correlates with a block of differentiation.
      Treatment of AML patients with DNA methyltransferase inhibitors results in global
      hypomethylation of genes and, thereby, can lead to a reactivation of the
      differentiation capability. Unfortunately, after termination of treatment both
      hypermethylation and differentiation block return in most cases. Here, we apply,
      for the first time, a computational model of epigenetic regulation of
      transcription to: i) provide a mechanistic understanding of the DNA (de-)
      methylation process in AML and; ii) improve DNA demethylation treatment
      strategies. By in silico simulation, we analyze promoter hypermethylation
      scenarios referring to DNMT dysfunction, decreased H3K4me3 and increased H3K27me3
      modification activity, and accelerated cell proliferation. We quantify
      differences between these scenarios with respect to gene repression and
      activation. Moreover, we compare the scenarios regarding their response to DNMT
      inhibitor treatment alone and in combination with inhibitors of H3K27me3 histone
      methyltransferases and of H3K4me3 histone demethylases. We find that the
      different hypermethylation scenarios respond specifically to therapy, suggesting
      that failure of remission originates in patient-specific deregulation. We observe
      that inappropriate demethylation therapy can result even in enforced
      deregulation. As an example, our results suggest that application of high DNMT
      inhibitor concentration can induce unwanted global gene activation if
      hypermethylation originates in increased H3K27me3 modification. Our results
      underline the importance of a personalized therapy requiring knowledge about the
      patient-specific mechanism of epigenetic deregulation.

PMID- 28758856
TI  - Clinicopathological characteristics and experience in the treatment of giant
      retroperitoneal liposarcoma: A case report and review of the literature.
AB  - Retroperitoneal liposarcoma (RPLS) is a rare tumor, especailly those over 20 kg
      that are called "giant liposarcoma," whose characteristics and treatments remain
      relatively unknown. Herein, we report a giant RPLS measuring 65 * 45 * 30 cm in
      diameter and 31 kg in weight, which we successfully performed complete excision
      through interdisciplinary cooperation. The patient had an uneventful
      postoperative course and was discharged without complications. Afterwards he
      underwent radiotherapy and had no evidence of tumor recurrence or symptoms of
      metastasis at 3-month CT scan and 8-month follow-up. We also first review the 13
      cases reported in literature published in PubMed regarding giant RPLS. Giant RPLS
      commonly occurs in adults aged 40-60 y and presents atypical clinical
      manifestations. CT scan is the most useful examination and preoperative biopsy is
      controversial. Complete surgical resection still remains the principal treatment.
      Giant RPLS can also be removed, even reach to R0 excision, by a multidisciplinary
      team in a specialized center after meticulous planning even though its gigantic
      tumor size. Local radiotherapy following surgery may improve the rate of
      recurrence. Besides, closely follow-up and routine examinations are required.

PMID- 28758857
TI  - Brain metastases in non-small cell lung cancer patients on epidermal growth
      factor receptor tyrosine kinase inhibitors: symptom and economic burden.
AB  - OBJECTIVE: This study describes the symptom and economic burden associated with
      brain metastases (BM) in patients with non-small cell lung cancer (NSCLC)
      receiving epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (EGFR-TKIs). METHODS: This retrospective study included adults with >=2 medical
      claims, within 90 days, for lung cancer and >=1 administration of EGFR-TKIs.
      Based on ICD-9 codes, patients were stratified into cohorts by type of metastases
      (BM, other metastases [OM], or no metastases [NM]), and by when the metastasis
      diagnosis occurred (synchronous or asynchronous). RESULTS: The population
      (synchronous BM [SBM] = 24, synchronous OM [SOM] = 23, asynchronous BM [ASBM] =
      15, asynchronous OM [ASOM] = 49, NM = 85) was mostly female (57%), average age 69
      years (SD = 11). SBM patients experienced more fatigue and nausea/vomiting
      compared with SOM and NM patients and more headaches and loss of appetite than NM
      patients. ASBM was associated with more fatigue, nausea/vomiting, headaches,
      pain/numbness, altered mental status, and seizures than NM, and more headaches
      and pain/numbness than ASOM. SBM patients experienced a greater increase in per
      member-per-month all-cause total healthcare costs after diagnosis ($20,301) vs
      SOM ($9,131, p = .001) and NM ($2,493, p = .001). ASBM's cost increase between
      baseline and follow-up ($7,867) did not differ from ASOM's ($4,947, p = .195);
      both were larger than NM ($2,493, p = .001 and p = .009, respectively).
      LIMITATIONS: EGFR mutation status was inferred based on EGFR-TKI treatment, not
      by molecular testing. Patients were from US commercial insurance plans; results
      may not be generalizable to other populations. CONCLUSIONS: Among patients with
      EGFR-TKI-treated NSCLC, patients with BM experienced more symptoms and, when
      diagnosed synchronously, had significant increases in total medical costs vs
      patients with OM and NM. Therapeutic options with central nervous system activity
      may offer advantages in symptomatology and costs in EGFR-mutated patients with
      BM.

PMID- 28758858
TI  - Swedish Cancer Society Radiation Therapy Research Investigation.
AB  - In an investigation by the Swedish Cancer Society, the present status, critical
      issues and future aspects and prospects were described by an expert group for
      each of nine major areas of radiation research. A summary of the investigation is
      presented in this report. A more extensive summary (in Swedish) can be found at
      www.Cancerfonden.se. It is concluded that radiation therapy plays an increasingly
      important role in curative and palliative tumour treatment and presents a
      considerable challenge to research. Several suggestions are made that could
      improve the possibilities for high-quality radiation therapy research in Sweden.

PMID- 28758859
TI  - Patients above Sixty Years Lymphoma Treated with a New Strategy of Age with
      Hodgkin's.
AB  - In the Swedish National Care Programme for Hodgkin's lymphoma (HL) a less
      intensive chemotherapy regimen with individualized dosing (LVPP/OEPA) was
      introduced in 1989. In total, 139 patients, 77 between 1985 and 1988 and 62
      between 1989 and 1992, were studied. Mean ages were 72 and 71 years,
      respectively. One hundred and nineteen patients were treated with curative
      intention, 63 (82%) between 1985 and 1988 vs. 56 (90%) between 1989 and 1992
      (p=0.11). All patients (13 vs. 20) treated with radiotherapy only achieved a
      complete remission (CR). The CR rates (67% vs. 65%) for patients treated with 6-8
      cycles of chemotherapy were also similar in the two time periods. The 5-year
      survival rate was 45% in the period 1985-1988 and 48% in 1989-1992. The survival
      of elderly HL patients was thus not improved from 1985-1988 to 1989-1992. Thus
      efforts to improve the chemotherapy regimen with individualized dosing did not
      change the outcome. Many patients experienced myelosuppression and opportunistic
      infections that may have contributed to the poor treatment results.

PMID- 28758860
TI  - New Techniques and Agents in the Adjuvant Therapy of Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma represents a major oncological challenge.
      Despite improvements in surgical techniques, long-term survival after resection
      is poor, with few patients surviving after 5 years. Until recently, there have
      been no large randomized trials of adjuvant therapy in pancreatic ductal
      adenocarcinoma. However, major trials such as the European Study Group for
      Pancreatic Cancer (ESPAC-1) and ESPAC-3 trials have set new standards for patient
      recruitment and development in this field. Adjuvant therapy has the potential to
      improve both patient survival and quality of life after curative resection.
      Currently, the best treatment is with 5-fluorouracil with folinic acid, but in
      the light of ongoing clinical trials, this may be supplanted by gemcitabine as
      the treatment of choice. Chemoradiotherapy does not appear to be beneficial in
      the adjuvant setting, but trials of a wide variety of other techniques and agents
      in the treatment of advanced disease are being undertaken and some of these will
      almost certainly be extended into the adjuvant setting in time. Great progress
      has been made in the adjuvant treatment of pancreatic cancer in the past 10 years
      and similar advances are likely over the next decade.

PMID- 28758861
TI  - Chalkley Estimates of Angiogenesis in Early Breast Cancer - Relevance to
      Prognosis.
AB  - The aim of this study was to investigate whether Chalkley estimates of
      angiogenesis add new knowledge regarding prediction of prognosis in 455
      consecutive early breast carcinomas, both node-positive (52%) and node-negative
      (48%). Median follow-up was 101 months. Intense vascularization indicated poor
      disease-specific (p=0.003) and overall (p=0.004) survival. In node-negative
      patients, Chalkley counts were not associated with prognosis, whereas in node
      positive patients, high Chalkley scores indicated poor disease-specific
      (p=0.0006) and overall (p=0.0008) survival. A multivariate analysis showed that
      positive lymph nodes, high histopathological grades, and negative oestrogen
      receptors were independent markers of cancer-related death. A high
      histopathological grade was associated with cancer-related death in node-negative
      patients, whereas in node-positive patients, many lymph nodes, high malignancy
      grade, negative oestrogen receptor, and increasing Chalkley counts (both tertiles
      and continuous) were independent markers of disease-specific death. Thus, in a
      univariate analysis it was found that high Chalkley estimates of angiogenesis
      indicated a poor prognosis, but high Chalkley estimates were independent
      prognostic markers only in node-positive patients.

PMID- 28758862
TI  - Radiation Therapy Through Activation of Stable Nuclides.
AB  - In an investigation by the Swedish Cancer Society, an expert group described the
      present status, critical issues and future aspects and potentials for each of
      nine major areas of radiation therapy research. This report deals with radiation
      therapy using activation of stable nuclides.

PMID- 28758863
TI  - Therapy with Radiopharmaceuticals.
AB  - In an investigation by the Swedish Cancer Society, an expert group described the
      present status, critical issues and future aspects and potentials for each of
      nine major areas of radiation therapy research. The present report deals with
      therapy with radiopharmaceuticals.

PMID- 28758864
TI  - Maintained Salivary Function after Brachytherapy in Patients with Head and Neck
      Carcinomas - Evaluation Using Quantitative Salivary Gland Scintigraphy.
AB  - The purpose of this study was to determine whether or not salivary gland
      dysfunction occurs within the first three months after brachytherapy in patients
      with head and neck carcinoma. Of the 20 patients with head and neck squamous cell
      carcinoma included in this study, 11 were treated with brachytherapy and the
      remaining 9 patients received external irradiation. All the patients underwent a
      salivary gland scintigraphy before and after radiotherapy. The scintigraphic
      parameters of each major salivary gland were then compared before and after the
      radiotherapy. In the brachytherapy group, none of the scintigraphic functional
      parameters showed a significant change before and after the radiotherapy. In
      contrast, all of the parameters with the exception of the uptake ratio (UR) of
      the submandibular glands significantly decreased after external irradiation. This
      observation was to be expected owing to the different irradiation doses
      administered by the two techniques. The scintigraphic technique used to evaluate
      salivary gland function should be used in future intensity-modulated radiation
      therapy salivary-gland-sparing studies in order to evaluate both the acute and
      chronic effects of irradiation in head and neck cancer patients.

PMID- 28758866
TI  - Liver Metastases from Colorectal Cancer - More Cures Awaiting?

PMID- 28758865
TI  - Patient Preference for Dissection of Sentinel Nodes Outside Level I-II of the
      Axilla.
AB  - In this study patients' and female doctors' opinions about harvesting sentinel
      nodes outside the axilla are evaluated and patients' ability to understand the
      concept of sentinel node biopsy is investigated. Information leaflets and
      questionnaires were mailed to 100 patients with breast cancer who had undergone
      sentinel node biopsy and to 300 female doctors. Seventy-three (73%) patients and
      148 (49%) female doctors returned the questionnaire. Fifty-eight (79%) breast
      cancer patients and 71 (48%) female doctors wanted harvesting to be done in order
      to determine whether the nodes were involved. Sixty-six (90%) patients and 128
      (86%) female doctors wanted the procedure if it changed the treatment. Sixty
      (82%) patients understood the outcome of the sentinel node procedure. Patients
      with breast cancer seem to value the information gained by harvesting sentinel
      nodes outside the axilla and want the procedure if there is even the slightest
      possibility that it might change the adjuvant treatment.

PMID- 28758867
TI  - Use of Alternative Medicine Among Norwegian Cancer Patients is Associated with
      Mental Distress - A Follow-up Study.
AB  - The purpose of this study was to investigate the relationship between the use of
      alternative medicine (AM) by cancer patients' and the level of self-perceived
      mental distress. One hundred and fifty-seven cancer patients were included in a
      longitudinal questionnaire-based study 12 months after their first contact with
      the Department of Oncology, University Hospital of Tromso, during the period 1990
      to 1991. Eligible patients received follow-up questionnaires after 24 and 60
      months recording their use of AM and measuring their perceived mental distress
      (GHQ-20). A total of 64 (41%) of the 157 patients who completed at least one
      questionnaire reported using AM one or more times during follow-up (ever-use).
      Between 65% and 79% of patients who were eligible at each point of the study
      completed the GHQ questionnaire. After 60 months of follow-up, 104 patients were
      still alive and 54 patients (52% of the survivors) had completed all the
      questionnaires. At inclusion in the study, significantly more AM users reported
      mental distress (57%) than non-users (20%) (p=0.001). After 24 and 60 months, the
      corresponding figures were 42% versus 29% (p=0.18), and 30% versus 10% (p=0.02),
      respectively. When adjusted for sex, age and disease progression, use of AM was
      found to be an independent factor highly associated with mental distress at 12
      months (OR=5.5, 95% CI 2.1-14.4). Later in the study, progression/relapse of
      cancer proved to be a more important predictor of mental distress. These findings
      suggest that, in North Norway, seeking alternative treatment is more common among
      mentally distressed cancer patients.

PMID- 28758868
TI  - Sensitizing and Protective Substances in Radiation Therapy and Predictive Assays.
AB  - In an investigation by the Swedish Cancer Society, an expert group described the
      present status, critical issues and future aspects and potentials for each of
      nine major areas of radiation therapy research. The present report deals with the
      use of sensitizing and protective substances in radiation therapy and predictive
      assays on normal tissues and tumour response.

PMID- 28758869
TI  - Acute and Late Toxicity Following Adjuvant High-Dose Chemotherapy for High-Risk
      Primary Operable Breast Cancer A Quality Assessment Study.
AB  - From 1996 to 2000, high-dose chemotherapy with haematopoietic stem-cell support
      was used as an adjuvant treatment strategy for management of primary high-risk
      breast cancer patients with more than five positive nodes. This single
      institution study included 52 women aged &#104 56 years with primary operable
      breast cancer and &#83 6 tumour-positive axillary lymph nodes. The treatment
      regimen consisted of at least three initial courses of FEC (5-fluorouracil,
      epirubicin, cyclophosphamide) followed by high-dose chemotherapy
      (cyclophosphamide, thiotepa, carboplatin) supported by autologous peripheral
      blood stem-cell reinfusion. This study focuses on quality control including
      evaluation of toxicity, supportive therapy and assessment of the stem-cell
      products. Cytokeratin 19 positive cells were found in the stem-cell product from
      3/37 patients. Data regarding organ toxicity were used for evaluation of short-
      and long-term side effects. Substantial acute toxicity and frequent catheter
      related infections were found. Long-term toxicities included reduced lung
      diffusion capacity (n=36), fatigue (n=14), arthralgia/myalgia (n=10),
      neurotoxicity (n=9) and memory loss (n=4). However, most toxicities were grade 1
      2 and reversible within two years. No treatment-related death occurred. Within a
      median follow-up of 30 months (range, 11-57), 25% of the patients had relapsed.
      Recurrence-free survival was 75% and overall survival was 88% three years after
      the start of treatment. Overall, high-dose chemotherapy was relatively well
      tolerated, with manageable toxicity and an acceptable requirement of supportive
      therapy. Until now, high-dose chemotherapy has not proven superior to
      conventional-dose adjuvant chemotherapy, therefore it is necessary in the future
      to focus on well-designed randomized studies.

PMID- 28758870
TI  - Medical Imaging for Improved Tumour Characterization, Delineation and Treatment
      Verification.
AB  - In an investigation by the Swedish Cancer Society, the present status, critical
      issues and future aspects and potentials were described by an expert group for
      each of nine major areas of radiation therapy research. This report deals with
      medical imaging for improved medical diagnosis including tumour detection,
      staging and characterization, treatment planning, guiding and verification,
      evaluation of response and treatment follow-up.

PMID- 28758871
TI  - Abstracts of Theses from the Nordic Countries.

PMID- 28758872
TI  - Interactions between Chemotherapy, Endocrine Therapy and Radiation.
AB  - In an investigation by the Swedish Cancer Society, an expert group described the
      present status, critical issues and future aspects and potentials for each of
      nine major areas of radiation therapy research. This report deals with
      interactions between chemotherapy, endocrine therapy, other anti-tumour drugs and
      radiation.

PMID- 28758873
TI  - Platelet aggregation during targeted temperature management after out-of-hospital
      cardiac arrest: A randomised clinical trial.
AB  - Some studies conclude that mild hypothermia causes platelet dysfunction leading
      to an increased bleeding risk, whereas others state that platelet aggregation is
      enhanced during mild hypothermia. Therefore, the aim of this study was to clarify
      whether standard or prolonged duration of targeted temperature management
      affected platelet aggregation. We randomised 82 comatose patients resuscitated
      after out-of-hospital cardiac arrest to either 24 hours (standard group) or 48
      hours (prolonged group) of targeted temperature management at 33+/-1 degrees C.
      Blood samples were collected 22 hours, 46 hours and 70 hours after reaching
      target temperature. Platelet aggregation was assessed by impedance aggregometry
      employing a Multiplate(r)Analyser, using the COLtest(r), TRAPtest(r), ADPtest(r)
      and ASPItest(r) as agonists, and with the results reported as area under the
      curve (AUC, AU*min). The platelet aggregation was below the normal range in all
      blood samples. No differences were observed between the standard group and the
      prolonged group in either of the blood samples (all p >= 0.11), except for a 24%
      decreased aggregation (95% confidence interval (CI) (10%;37%), p = 0.002) when
      using the COLtest(r) in the 46-hour sample. Comparing the 22-hour sample with the
      46-hour sample in the prolonged group separately, we found no differences when
      employing the COLtest(r), the ASPItest(r) or the ADPtest(r) in patients without
      the use of adenosine diphosphate receptor inhibitors (all p values >=0.21), but
      aggregation induced by the TRAPtest(r) decreased by 14% (95% CI -8%;-20%), p <
      0.001). We concluded that the platelet aggregation post cardiac arrest was below
      the normal range independent of the core temperature. Moreover, no substantial
      difference was found in platelet aggregation between standard and prolonged
      targeted temperature management.

PMID- 28758874
TI  - Sulfide as an alternative electron donor to glucose for power generation in
      mediator-less microbial fuel cell.
AB  - The objective of this study was to investigate the power generation in a dual
      chamber microbial fuel cell (MFC). As one of the effective parameters, glucose
      concentration was studied in the range of 100-1000 mg/L. At the optimum
      concentration of 500 mg/L of glucose, maximum power generation was 186 mW/m2. As
      an alternative, sulfide was used as an electron donor and maximum power output
      was 401 mW/m2 at the concentration of 100 mg/L; which was more than twice of
      power produced using glucose. Moreover, sulfide removal efficiencies of 70%, 66%,
      60%, and 64% were obtained when initial sulfide concentrations of 10, 20, 80, and
      100 mg/L were used, respectively.

PMID- 28758875
TI  - Functional optimization of agonistic antibodies to OX40 receptor with novel Fc
      mutations to promote antibody multimerization.
AB  - Immunostimulatory receptors belonging to the tumor necrosis factor receptor
      (TNFR) superfamily are emerging as promising targets for cancer immunotherapies.
      To optimize the agonism of therapeutic antibodies to these receptors, Fc
      engineering of antibodies was applied to facilitate the clustering of cell
      surface TNFRs to activate downstream signaling pathways. One engineering strategy
      is to identify Fc mutations that facilitate antibody multimerization on the cell
      surface directly. From the analyses of the crystal packing of IgG1 structures, we
      identified a novel set of Fc mutations, T437R and K248E, that facilitated
      antibody multimerization upon binding to antigens on cell surface. In a NF-kappaB
      reporter assay, the engineered T437R/K248E mutations could facilitate enhanced
      agonism of an anti-OX40 antibody without the dependence on FcgammaRIIB
      crosslinking. Nonetheless, the presence of cells expressing FcgammaRIIB could
      facilitate a boost of the agonism of the engineered antibody with mutations on
      IgG1 Fc, but not on the silent IgG2sigma Fc. The Fc engineered antibody also
      showed enhanced effector functions, including antibody-dependent cell-meditated
      cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent
      cytotoxicity, depending on the IgG subtypes. Also, the engineered antibodies
      showed normal FcRn binding and pharmacokinetic profiles in mice. In summary, this
      study elucidated a novel Fc engineering approach to promote antibody
      multimerization on a cell surface, which could enhance agonism and improve
      effector function for anti-TNFR antibodies as well as other therapeutic
      antibodies.

PMID- 28758876
TI  - WRKY45 phosphorylation at threonine 266 acts negatively on WRKY45-dependent blast
      resistance in rice.
AB  - WRKY45 is a central regulator of disease resistance mediated by salicylic acid
      signaling in rice and its activation involves phosphorylation by OsMPK6. OsMPK6
      phosphorylates WRKY45 at Thr266, Ser294, and Ser299 in vitro. Phosphorylation of
      Ser294 and/or Ser299 is required for full activation of WRKY45, but the
      importance of Thr266 phosphorylation has remained unknown. Here, we report on the
      characterization of Thr266 phosphorylation of WRKY45 in rice. Transient
      expression of mutant WRKY45 revealed that Thr266 is phosphorylated in vivo,
      together with Ser294/299. Replacement of Thr266 by Asn did not affect the
      enhanced Magnaporthe oryzae resistance afforded by WRKY45 overexpression. By
      contrast, replacement by Asp negated the enhancement of M. oryzae resistance.
      These results suggest that Thr266 phosphorylation acts negatively on WRKY45
      dependent disease resistance.

PMID- 28758877
TI  - The effects of metal ion contaminants on the double stranded DNA helix and
      diseases.
AB  - Mineral metal ions are essential for the maintenance of the reactions that
      regulate homeostasis and the functions of our body. It is known that the
      regulation of the neurodegenerative system depends directly on life metal ions,
      such as Na, K, Mg, Ca, Fe, Mo, Cu, Co, Zn, Cr, Mn, while the toxic metals Cd, Pb,
      Hg, etc disturb homeostasis, leading to diseases. Particularly significant is the
      effect of toxic metals on the double stranded forms of DNA and conformations. It
      was found that the toxic metal ions by reacting specifically with the nucleic
      bases and electrostatically with the negatively phosphate groups of the DNA
      backbone cause changes in the structure of the DNA double helix, leading to
      breaks of single or double strands. Accumulation of these defects affects the
      protecting systems of the body and induces mutations, eventually leading to
      serious diseases. There are many metal ions, such as Cr, Al, Cd, Cu, Ni, which by
      binding directly to DNA molecule or by developing oxidative stress increase the
      instability of DNA, promoting epigenetic changes that lead to DNA damage. Toxic
      metal ions induce indirect DNA damage and influence the gene stability by
      inactivating encoding proteins or by changing the redox potential and the
      signaling of metalloenzymes.

PMID- 28758878
TI  - DNA binding affinity of a macrocyclic copper(II) complex: Spectroscopic and
      molecular docking studies.
AB  - The interaction of a novel macrocyclic copper(II) complex, ([CuL(ClO4)2] that L
      is 1,3,6,10,12,15-hexaazatricyclo[13.3.1.16,10]eicosane) with calf thymus DNA (ct
      DNA) was investigated by various physicochemical techniques and molecular docking
      at simulated physiological conditions (pH = 7.4). The absorption spectra of the
      Cu(II) complex with ct-DNA showed a marked hyperchroism with 10 nm blue shift.
      The intrinsic binding constant (Kb) was determined as 1.25 * 104 M-1, which is
      more in keeping with the groove binding with DNA. Furthermore, competitive
      fluorimetric studies with Hoechst33258 have shown that Cu(II) complex exhibits
      the ability to displace the ct-DNA-bound Hoechst33258 indicating that it binds to
      ct-DNA in strong competition with Hoechst33258 for the groove binding. Also, no
      change in the relative viscosity of ct-DNA and fluorescence intensity of ct-DNA
      MB complex in the present of Cu(II) complex is another evidence to groove
      binding. The thermodynamic parameters are calculated by van't Hoff equation,
      which demonstrated that hydrogen bonds and van der Waals interactions played
      major roles in the binding reaction. The experimental results were in agreement
      with the results obtained via molecular docking study.

PMID- 28758880
TI  - Testing emotional memories: does negative emotional significance influence the
      benefit received from testing?
AB  - A large body of research shows that emotionally significant stimuli are better
      stored in memory. One question that has received much less attention is how
      emotional memories are influenced by factors that influence memories after the
      initial encoding of stimuli. Intriguingly, several recent studies suggest that
      post-encoding factors do not differ in their effects on emotional and neutral
      memories. However, to date, only detrimental factors have been addressed. In the
      present study, we examined whether emotionally negative memories are
      differentially influenced by a well-known beneficial factor: the testing of
      memories. We employed a standard cued recall testing-effect paradigm where
      participants studied cue-target pairs for negative and neutral target pictures.
      In a subsequent post-encoding phase, one third of the cue-target pairs were
      tested and one third restudied; the remaining third served as control pairs.
      After one week, memory for all cue-target pairs was tested. While replicating
      both the testing effect and the emotional enhancement effect, no differences
      between negative and neutral memories in the benefits received from testing and
      restudying were observed. Thus, it seems to be true that post-encoding factors do
      not influence emotional memories in any other way than neutral memories, even
      when they are beneficial.

PMID- 28758879
TI  - Genome-wide analysis of cytosine DNA methylation revealed salicylic acid promotes
      defense pathways over seedling development in pearl millet.
AB  - Cytosine DNA methylation is an epigenetic regulatory system used by plants to
      control gene expression. Methylation pattern always changes after abiotic
      stresses, pathogens and pest infections or after a treatment with salicylic acid
      (SA). The latter is a key player in plant development and defense against insect
      herbivores, pathogens, and abiotic stresses. The roles of SA on the methylation
      patterns and the plant development were performed in 4 pearl millet (Pennisetum
      glaucum) varieties. Seedlings of 4 early-flowering photosensitive genotypes
      (PMS3, PMI8, PMG, and PMT2) were grown on MS medium supplemented with null or
      different doses of SA. Root growth was used as a parameter to evaluate the
      effects of SA at early stage development. DNA from these seedlings was extracted
      and Methylation-Sensitive Amplified Polymorphism (MSAP) was measured to assess
      the effects of SA on methylome. The methylation analysis revealed that SA
      treatment decreased the methylation, while inhibiting the root growth for all
      varieties tested, except in PMG at 0.5 mM, indicating a dose and a genotype
      response-dependence. The methylation level was positively correlated with the
      root growth. This suggests that SA influences both the methylome by demethylation
      activities and the root growth by interfering with the root development
      responsive genes. The demethylation process, induced by the REPRESSOR OF
      SILCENCING 1 (ROS1) may activate R genes, or GH3.5 and downregulate the hormonal
      pathway under root development. These findings showed the pearl millet metabolism
      prioritized and promoted the defense pathways over vegetative development during
      stress.

PMID- 28758881
TI  - Preparation and characterization of CuO catalyst for the thermolysis treatment of
      distillery wastewater.
AB  - CuO catalyst was prepared from copper sulfate by alkali precipitation method
      followed by drying and calcination. Characterization of CuO catalyst using X-ray
      diffraction, Brunauer-Emmett-Teller, and Barrett-Joyner-Halenda surface area
      analysis envisaged the effectiveness of CuO as a catalyst for the treatment of
      biodigester effluent (BDE) emanated from distilleries. The catalytic thermolysis
      is an efficient advance treatment method for distillery biodigester effluent
      (BDE). CT treatment of BDE was carried out in a 0.5 dm3 thermolytic batch reactor
      using CuO as a catalyst at different pH (1-9), temperatures (80-110 degrees C),
      and catalyst loadings (1-4 kg/m3). With CuO catalyst, a temperature of 110
      degrees C, catalyst loading of 4 kg/m3, and pH of 2 was found to be optimal,
      providing a maximum reduction in chemical oxygen demand of 65%. The settling
      characteristics at different temperatures of CT-treated sludge were also
      presented.

PMID- 28758883
TI  - Application of the DSM-5 Level of Personality Functioning Scale by Lay Raters.
AB  - One concern that has been expressed with the Alternative Model for Personality
      Disorders (AMPD) presented in DSM-5 is that the description of characteristic
      impairments in personality function uses concepts requiring considerable
      experience and clinical inference to apply. To examine this question, the
      individual indicators included in the AMPD's Level of Personality Functioning
      Scale (LPFS) that describes these core impairments were abstracted as individual
      items, and then rated on a target acquaintance by 194 undergraduate college
      students with minimal training in personality disorder and no training in the
      AMPD. Results indicated that the LPFS indicators were highly internally
      consistent as rated in this sample, and that the degree of discrimination between
      groups corresponded very well with the putative level of severity represented for
      each indicator in the LPFS. These findings support the contention that using the
      LPFS might not require any particular clinical experience or training.

PMID- 28758882
TI  - Attitude towards gender roles and violence against women and girls (VAWG):
      baseline findings from an RCT of 1752 youths in Pakistan.
AB  - BACKGROUND: Violence against women is driven by gender norms that normalize and
      justify gender inequality and violence. Gender norms are substantially shaped
      during adolescence. Programs offered through schools offer an opportunity to
      influence gender attitudes toward gender equity if we understand these to be
      partly shaped by peers and the school environment. OBJECTIVE: We present an
      analysis of the baseline research conducted for a randomized controlled trial
      with 1752 grade 6 boys and girls and their attitudes toward gender roles, VAWG,
      and associated factors. METHODS: We used baseline data from a  cluster randomised
      control study. Interviews were conducted in 40 public schools in Hyderabad, with
      25-65 children per school. Questions were asked about attitudes toward gender
      roles, peer-to-peer perpetration, and victimization experiences, and family life,
      including father- or in-law-to- mother violence and food security. Multiple
      regression models were built of factors associated with gender attitudes for boys
      and girls. RESULTS: Our result have shown youth attitudes endorsing patriarchal
      gender beliefs were higher for boys, compared to girls. The multiple regression
      model showed that for boys, patriarchal gender attitudes were positively
      associated with hunger, depression, being promised already in marriage, and being
      a victim and/or perpetrator of peer violence. For girls gender attitudes were
      associated with hunger, experiencing corporal punishment at home, and being a
      perpetrator (for some, and victim) of peer violence. CONCLUSION: Youth
      patriarchal attitudes are closely related to their experience of violence at
      school and for girl's physical punishment, at home and for boys being promised in
      early marriage. We suggest that these variables are indicators of gender norms
      among peers and in the family. The significance of peer norms is that it provides
      the possibility that school-based interventions which work with school peers have
      the potential to positively impact youth patriarchal gender attitudes and foster
      attitudes of gender equality and respect, and potentially to decrease youth
      victimization and perpetration.

PMID- 28758884
TI  - Clinical Characteristics of Comorbid Narcissistic Personality Disorder in
      Patients With Borderline Personality Disorder.
AB  - This study examines psychopathology and clinical characteristics of patients with
      borderline personality disorder (BPD) and comorbid narcissistic personality
      disorder (NPD) from two international randomized controlled trials. From a
      combined sample of 188 patients with BPD, 25 also fulfilled criteria for a
      comorbid diagnosis of NPD according to DSM-IV. The BPD patients with comorbid
      NPD, compared to the BPD patients without comorbid NPD, showed significantly more
      BPD criteria (M = 7.44 vs. M = 6.55, p < .001), fulfilled more criteria of
      comorbid histrionic (M = 3.84 vs. M = 1.98, p < .001), paranoid (M = 3.12 vs. M =
      2.27, p = .014), and schizotypal (M = 1.64 vs. M = 1.02, p = .018) personality
      disorders, and were more likely to meet criteria for full histrionic PD diagnosis
      (44.0% vs. 14.2%, p < .001). The BPD-NPD group also reported significantly fewer
      psychiatric hospitalizations in the previous year (M = 0.40 vs. M = 0.82, p =
      .019) and fewer axis I disorders (M = 2.68 vs. M = 3.75, p = .033). No
      differences could be found in general functioning, self-harming behavior, and
      suicide attempts.

PMID- 28758885
TI  - Dimensional Traits of Schizotypy Associated With Glycine Receptor GLRA1
      Polymorphism: An Exploratory Candidate-Gene Association Study.
AB  - Schizotypy captures the underlying genetic vulnerability to schizophrenia.
      However, the genetic underpinnings of schizotypy remain unexplored. The authors
      examined the relationship between single nucleotide poly-morphisms (SNPs) and
      schizotypy. A sample of 137 subjects (43 healthy controls, 34 subjects with
      schizotypal personality disorder [SPD], 32 with borderline personality disorder,
      and 25 with other personality disorders) completed the Schizotypal Personality
      Questionnaire (SPQ). Subjects were genotyped using a custom array chip. Principal
      component analysis was used to cluster SPQ variables. Linear regression tested
      for associations between dimensional schizotypy and SNPs. Logistic regression
      tested for associations between SNPs and SPD diagnosis. There were significant
      associations between the minor alleles of three SNPs within the glycine receptor
      alpha 1 subunit (GLRA1) and the disorganized schizotypy dimension, even after
      Bonferroni correction. There were no significant associations between any SNPs
      and the categorical SPD diagnosis. Glycine receptor pathways may have an impact
      on dimensional traits of psychosis.

PMID- 28758886
TI  - Personality, Schizophrenia, and Violence: A Longitudinal Study.
AB  - The aims of this study were (a) to investigate the presence of clinically
      significant personality traits and personality disorders (PD) in patients living
      in residential facilities, with or without a history of violence (69 and 46,
      respectively); and (b) to investigate any associations between clinically
      significant personality traits and PDs, aggression, impulsivity, hostility, and
      violent behavior during a 1-year follow-up. The most frequent primary diagnoses
      were schizophrenia (58.3%) and PD (20.9%). Those with a history of violence
      demonstrated more antisocial and alcohol dependence features and lower depressive
      PD symptoms than the control group. Hostility levels, antisocial symptoms, and
      drug dependence, as well as a Structured Clinical Interview for DSM-IV Axis II
      diagnosis of PD, predicted aggressive and violent behavior during follow-up. The
      study confirms the relevance of assessing PDs both to evaluate the risk of
      violent behavior and to plan appropriate preventive and treatment intervention.

PMID- 28758887
TI  - Dazzled by the dominions of dopamine: clinical roles of D3, D2, and D1 receptors.
AB  - Unravelling the mystery of dopamine neurotransmission, especially at its 3 most
      clinically relevant receptors, D3, D2, and D1, helps explain the pathophysiology
      of numerous psychiatric and neurologic symptoms in various CNS disorders that are
      theoretically caused by dysregulation of this neurotransmitter.

PMID- 28758888
TI  - Bedaquiline and Delamanid Combination Treatment of 5 Patients with Pulmonary
      Extensively Drug-Resistant Tuberculosis.
AB  - We report the experiences of 5 patients taking bedaquiline with delamanid in
      combination: 1 patient was cured; 3 culture converted, with 2 continuing and 1
      changing therapy; and 1 died from respiratory insufficiency. For 2 patients, QT
      interval prolongation but no arrhythmias occurred. Use of this therapy is
      justified for patients with limited options.

PMID- 28758889
TI  - Off-Label Use of Bedaquiline in Children and Adolescents with Multidrug-Resistant
      Tuberculosis.
AB  - We describe 27 children and adolescents <18 years of age who received bedaquiline
      during treatment for multidrug-resistant tuberculosis. We report good treatment
      responses and no cessation attributable to adverse effects. Bedaquiline could be
      considered for use with this age group for multidrug-resistant tuberculosis when
      treatment options are limited.

PMID- 28758891
TI  - Form and function in the Lower Palaeolithic: history, progress, and continued
      relevance.
AB  - Percussively flaked stone artefacts constitute a major source of evidence
      relating to hominin behavioural strategies and are, essentially, a product or
      byproduct of a past individual's decision to create a tool with respect to some
      broader goal. Moreover, it has long been noted that both differences and
      recurrent regularities exist within and between Palaeolithic stone artefact
      forms. Accordingly, archaeologists have frequently drawn links between form and
      functionality, with functional objectives and performance often being regarded
      consequential to a stone tool's morphological properties. Despite these factors,
      extensive reviews of the related concepts of form and function with respect to
      the Lower Palaeolithic remain surprisingly sparse. We attempt to redress this
      issue. First we stress the historical place of form-function concepts, and their
      role in establishing basic ideas that echo to this day. We then highlight
      methodological and conceptual progress in determining artefactual function in
      more recent years. Thereafter, we evaluate four specific issues that are of
      direct consequence for evaluating the ongoing relevance of form-function
      concepts, especially with respect to their relevance for understanding human
      evolution more generally. Our discussion highlights specifically how recent
      developments have been able to build on a long historical legacy, and demonstrate
      that direct, indirect, experimental, and evolutionary perspectives intersect in
      crucial ways, with each providing specific but essential insights for ongoing
      questions. We conclude by emphasising that our understanding of these issues and
      their interaction, has been, and will be, essential to accurately interpret the
      Lower Palaeolithic archaeological record, tool-form related behaviours of Lower
      Palaeolithic hominins, and their consequences for (and relationship to) wider
      questions of human evolution.

PMID- 28758892
TI  - What is race today? Scientific, legal, and social appraisals from around the
      globe.

PMID- 28758893
TI  - Enhancing ER stress in myeloma.

PMID- 28758890
TI  - Structural basis for plant plasma membrane protein dynamics and organization into
      functional nanodomains.
AB  - Plasma Membrane is the primary structure for adjusting to ever changing
      conditions. PM sub-compartmentalization in domains is thought to orchestrate
      signaling. Yet, mechanisms governing membrane organization are mostly
      uncharacterized. The plant-specific REMORINs are proteins regulating hormonal
      crosstalk and host invasion. REMs are the best-characterized nanodomain markers
      via an uncharacterized moiety called REMORIN C-terminal Anchor. By coupling
      biophysical methods, super-resolution microscopy and physiology, we decipher an
      original mechanism regulating the dynamic and organization of nanodomains. We
      showed that targeting of REMORIN is independent of the COP-II-dependent secretory
      pathway and mediated by PI4P and sterol. REM-CA is an unconventional lipid
      binding motif that confers nanodomain organization. Analyses of REM-CA mutants by
      single particle tracking demonstrate that mobility and supramolecular
      organization are critical for immunity. This study provides a unique mechanistic
      insight into how the tight control of spatial segregation is critical in the
      definition of PM domain necessary to support biological function.

PMID- 28758894
TI  - Synergistic SNGI-TKI combination against LSCs.

PMID- 28758897
TI  - Skew scattering dominated anomalous Hall effect in Co x (MgO)100-x granular thin
      films.
AB  - We investigated the mechanism(s) of the anomalous Hall effect (AHE) in magnetic
      granular materials by fabricating 100 nm-thick thin films of Co x (MgO)100-x with
      a Co volume fraction of 34  ?  x  ?  100 using co-sputtering at room temperature.
      We measured the temperature dependence of longitudinal resistivity ([Formula: see
      text]) and anomalous Hall resistivity ([Formula: see text]) from 5 K to 300 K in
      all samples. We found that when x decreases from 100 to 34, the values of
      [Formula: see text] and [Formula: see text] respectively increased by about four
      and three orders in magnitude. By linearly fitting the data, obtained at 5 K, of
      anomalous Hall coefficient ([Formula: see text]) and of [Formula: see text] to
      [Formula: see text], we found that our results perfectly fell on a straight line
      with a slope of [Formula: see text] 0.97  +/-  0.02. This fitting value of
      [Formula: see text] in [Formula: see text] clearly suggests that skew scattering
      dominated the AHE in this granular system. To explore the effect of the
      scattering on the AHE, we performed the same measurements on annealed samples. We
      found that although both [Formula: see text] and [Formula: see text]
      significantly reduced after annealing, the correlation between them was almost
      the same, which was confirmed by the fitted value, [Formula: see text]  =  0.99 
      +/-  0.03. These data strongly suggest that the AHE originates from the skew
      scattering in Co-MgO granular thin films no matter how strong the scattering of
      electrons by the interfaces and defects is. This observation may be of importance
      to the development of spintronic devices based on MgO.

PMID- 28758895
TI  - HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA
      binding protein MAA-1.
AB  - In yeast, the broadly conserved acyl-CoA-binding protein (ACBP) is a negative
      regulator of stress resistance and longevity. Here, we have turned to the
      nematode C. elegans as a model organism in which to determine whether ACBPs play
      similar roles in multicellular organisms. We systematically inactivated each of
      the seven C. elegans ACBP paralogs and found that one of them, maa-1 (which
      encodes membrane-associated ACBP 1), is indeed involved in the regulation of
      longevity. In fact, loss of maa-1 promotes lifespan extension and resistance to
      different types of stress. Through genetic and gene expression studies we have
      demonstrated that HIF-1, a master transcriptional regulator of adaptation to
      hypoxia, plays a central role in orchestrating the anti-aging response induced by
      MAA-1 deficiency. This response relies on the activation of molecular chaperones
      known to contribute to maintenance of the proteome. Our work extends to C.
      elegans the role of ACBP in aging, implicates HIF-1 in the increase of lifespan
      of maa-1-deficient worms, and sheds light on the anti-aging function of HIF-1.
      Given that both ACBP and HIF-1 are highly conserved, our results suggest the
      possible involvement of these proteins in the age-associated decline in
      proteostasis in mammals.

PMID- 28758898
TI  - MoS2-supported gold nanoparticle for CO hydrogenation.
AB  - Employing dispersion-corrected density functional theory, we examine the
      geometry, electronic structure, and reactivity of 13-atom Au nanoparticle
      supported on defect-laden single-layer MoS2. The planar structure of Au13 favored
      in isolated phase, transforms into the three-dimensional structure when supported
      on MoS2. We find that charge is transferred from MoS2 to Au13, and that the
      electron density is also distributed away from the Au13/MoS2 interfacial region
      making Au sites away from the interface catalytically active. Owing to effect of
      the support, the Au d states become narrower, and the frontier states appear
      close to the Fermi level. Consequently, in contrast to the reactivity of
      Au13/TiO2 toward methanol decomposition, Au13/MoS2 offers excellent activity
      toward methanol synthesis, as demonstrated here, via CO hydrogenation.

PMID- 28758896
TI  - Chemo brain or tumor brain - that is the question: the presence of extracranial
      tumors profoundly affects molecular processes in the prefrontal cortex of
      TumorGraft mice.
AB  - Cancer chemotherapy causes numerous persistent central nervous system
      complications. This condition is known as chemo brain. Cognitive impairments
      occur even before treatment, and hence are referred to as cancer associated
      cognitive changes, or tumor brain. There is much yet to be learned about the
      mechanisms of both chemo brain and tumor brain. The frequency and timing of chemo
      brain and tumor brain occurrence and persistence strongly suggest they may be
      epigenetic in nature and associated with altered gene expression. Here we used
      TumorGraftTM models wherein part of a patient's tumor is removed and grafted into
      immune-deficient mice and conducted global gene expression and DNA methylation
      analysis. We show that malignant non-central nervous system tumor growth causes
      profound molecular alterations in the brain. Mice harbouring triple negative or
      progesterone positive breast cancer TumorGrafts exhibited altered gene
      expression, decreased levels of DNA methylation, increased levels of DNA
      hydroxymethylation, and oxidative stress in the prefrontal cortex. Interestingly,
      chemotherapy did not have any additional synergistic effects on the analyzed
      processes. The molecular changes observed in this study are known signs of
      neurodegeneration and brain aging. This study provides an important roadmap for
      future large-scale analysis of the molecular and cellular mechanisms of tumor
      brain.

PMID- 28758899
TI  - A flexible, transparent and high-performance gas sensor based on layer-materials
      for wearable technology.
AB  - Gas sensors play a vital role among a wide range of practical applications.
      Recently, propelled by the development of layered materials, gas sensors have
      gained much progress. However, the high operation temperature has restricted
      their further application. Herein, via a facile pulsed laser deposition (PLD)
      method, we demonstrate a flexible, transparent and high-performance gas sensor
      made of highly-crystalline indium selenide (In2Se3) film. Under UV-vis-NIR light
      or even solar energy activation, the constructed gas sensors exhibit superior
      properties for detecting acetylene (C2H2) gas at room temperature. We attribute
      these properties to the photo-induced charger transfer mechanism upon C2H2
      molecule adsorption. Moreover, no apparent degradation in the device properties
      is observed even after 100 bending cycles. In addition, we can also fabricate
      this device on rigid substrates, which is also capable to detect gas molecules at
      room temperature. These results unambiguously distinguish In2Se3 as a new
      candidate for future application in monitoring C2H2 gas at room temperature and
      open up new opportunities for developing next generation full-spectrum activated
      gas sensors.

PMID- 28758900
TI  - TNF is required for TLR ligand-mediated but not protease-mediated allergic airway
      inflammation.
AB  - Asthma is associated with exposure to a wide variety of allergens and adjuvants.
      The extent to which overlap exists between the cellular and molecular mechanisms
      triggered by these various agents is poorly understood, but it might explain the
      differential responsiveness of patients to specific therapies. In particular, it
      is unclear why some, but not all, patients benefit from blockade of TNF. Here, we
      characterized signaling pathways triggered by distinct types of adjuvants during
      allergic sensitization. Mice sensitized to an innocuous protein using TLR ligands
      or house dust extracts as adjuvants developed mixed eosinophilic and neutrophilic
      airway inflammation and airway hyperresponsiveness (AHR) following allergen
      challenge, whereas mice sensitized using proteases as adjuvants developed
      predominantly eosinophilic inflammation and AHR. TLR ligands, but not proteases,
      induced TNF during allergic sensitization. TNF signaled through airway epithelial
      cells to reprogram them and promote Th2, but not Th17, development in lymph
      nodes. TNF was also required during the allergen challenge phase for neutrophilic
      and eosinophilic inflammation. In contrast, TNF was dispensable for allergic
      airway disease in a protease-mediated model of asthma. These findings might help
      to explain why TNF blockade improves lung function in only some patients with
      asthma.

PMID- 28758901
TI  - Stromal cell cadherin-11 regulates adipose tissue inflammation and diabetes.
AB  - M2 macrophages, innate lymphoid type 2 cells (ILC2s), eosinophils, Tregs, and
      invariant NK T cells (iNKT cells) all help to control adipose tissue
      inflammation, while M1 macrophages, TNF, and other inflammatory cytokines drive
      inflammation and insulin resistance in obesity. Stromal cells regulate leukocyte
      responses in lymph nodes, but the role of stromal cells in adipose tissue
      inflammation is unknown. PDGFRalpha+ stromal cells are major producers of IL-33
      in adipose tissue. Here, we show that mesenchymal cadherin-11 modulates stromal
      fibroblast function. Cadherin-11-deficient mice displayed increased stromal
      production of IL-33, with concomitant enhancements in ILC2s and M2 macrophages
      that helped control adipose tissue inflammation. Higher expression levels of IL
      33 in cadherin-11-deficient mice mediated ILC2 activation, resulting in higher IL
      13 expression levels and M2 macrophage expansion in adipose tissue. Consistent
      with reduced adipose tissue inflammation, cadherin-11-deficient mice were
      protected from obesity-induced glucose intolerance and adipose tissue fibrosis.
      Importantly, anti-cadherin-11 mAb blockade similarly improved inflammation and
      glycemic control in obese WT mice. These results suggest that stromal fibroblasts
      expressing cadherin-11 regulate adipose tissue inflammation and thus highlight
      cadherin-11 as a potential therapeutic target for the management of obesity.

PMID- 28758902
TI  - GATA4 loss of function in liver cancer impedes precursor to hepatocyte
      transition.
AB  - The most frequent chromosomal structural loss in hepatocellular carcinoma (HCC)
      is of the short arm of chromosome 8 (8p). Genes on the remaining homologous
      chromosome, however, are not recurrently mutated, and the identity of key 8p
      tumor-suppressor genes (TSG) is unknown. In this work, analysis of minimal
      commonly deleted 8p segments to identify candidate TSG implicated GATA4, a master
      transcription factor driver of hepatocyte epithelial lineage fate. In a murine
      model, liver-conditional deletion of 1 Gata4 allele to model the
      haploinsufficiency seen in HCC produced enlarged livers with a gene expression
      profile of persistent precursor proliferation and failed hepatocyte epithelial
      differentiation. HCC mimicked this gene expression profile, even in cases that
      were morphologically classified as well differentiated. HCC with intact
      chromosome 8p also featured GATA4 loss of function via GATA4 germline mutations
      that abrogated GATA4 interactions with a coactivator, MED12, or by inactivating
      mutations directly in GATA4 coactivators, including ARID1A. GATA4 reintroduction
      into GATA4-haploinsufficient HCC cells or ARID1A reintroduction into ARID1A
      mutant/GATA4-intact HCC cells activated hundreds of hepatocyte genes and quenched
      the proliferative precursor program. Thus, disruption of GATA4-mediated
      transactivation in HCC suppresses hepatocyte epithelial differentiation to
      sustain replicative precursor phenotype.

PMID- 28758904
TI  - Parathyroid hormone regulates fates of murine osteoblast precursors in vivo.
AB  - Teriparatide, a recombinant form of parathyroid hormone (PTH), is the only
      approved treatment for osteoporosis that increases the rate of bone formation.
      Teriparatide increases osteoblast numbers by suppressing osteoblast apoptosis and
      activating bone-lining cells. No direct evidence for teriparatide's actions on
      early cells of the osteoblast lineage has been demonstrated. Here, we have
      employed a lineage-tracing strategy that uses a tamoxifen-dependent, promoter
      driven cre to mark early cells of the osteoblast lineage in adult mice. We show
      that teriparatide increases the numbers of osteoblast precursors and drives their
      differentiation into mature osteoblasts. Unexpectedly, following withdrawal of
      teriparatide therapy, bone marrow adipocytes increased dramatically in number.
      Some of these adipocytes derived from cells marked by Sox9-cre expression weeks
      earlier. Continued therapy with teriparatide prevented the appearance of
      adipocytes. Selective, inducible deletion of the PTH receptor in Sox9-cre cells
      demonstrated that PTH receptor expression is required for teriparatide-mediated
      increases in early osteoblast precursors. The increase in early precursors after
      teriparatide administration was associated with robust suppression of precursor
      apoptosis without affecting their rate of proliferation. Thus, teriparatide
      increases the numbers of early cells of the osteoblast lineage, hastens their
      differentiation into osteoblasts, and suppresses their differentiation into
      adipocytes in vivo.

PMID- 28758903
TI  - Transcriptional control of microglia phenotypes in health and disease.
AB  - Microglia are the main resident macrophage population of the CNS and perform
      numerous functions required for CNS development, homeostasis, immunity, and
      repair. Many lines of evidence also indicate that dysregulation of microglia
      contributes to the pathogenesis of neurodegenerative and behavioral diseases.
      These observations provide a compelling argument to more clearly define the
      mechanisms that control microglia identity and function in health and disease. In
      this Review, we present a conceptual framework for how different classes of
      transcription factors interact to select and activate regulatory elements that
      control microglia development and their responses to internal and external
      signals. We then describe functions of specific transcription factors in normal
      and pathological contexts and conclude with a consideration of open questions to
      be addressed in the future.

PMID- 28758905
TI  - Neuropeptide FF increases M2 activation and self-renewal of adipose tissue
      macrophages.

PMID- 28758907
TI  - The "Sandwich Therapy": A Microsurgical Integrated Approach for Presternal Keloid
      Treatment.
AB  - BACKGROUND: Keloid therapy remains a great challenge for plastic surgeons,
      especially when the defect cannot be closed primarily, necessitating tissue
      transplantation. Here, we introduce a new treatment modality, called the sandwich
      therapy, for presternal keloids; the sandwich therapy incorporates
      preradiotherapy, superficial circumflex iliac artery perforator (SCIP) flap
      transplantation, and postradiotherapy. METHODS: From December 2012 to October
      2013, 12 patients received the "sandwich therapy." For the protocol, all patients
      went through 5 days of specific events: the precut procedure, preradiotherapy,
      resection and SCIP flap transplantation, donor site radiotherapy, and final
      presternal radiotherapy. RESULTS: All the flaps survived completely. No
      complication was observed during the perioperative period. With a mean follow-up
      of 12 months, only 1 case was reported with an incisional hypertrophic scar. In
      all patients, the main discomfort complaints were resolved postoperatively.
      CONCLUSIONS: A low-tension or without-tension closure could be achieved with SCIP
      flap transplantation. The perioperative radiotherapy could further lower the risk
      of keloid recurrence. The sandwich therapy provides a new surgical approach to
      presternal keloid treatment.

PMID- 28758908
TI  - Targeting Apoptotic Activity Against Prostate Cancer Stem Cells.
AB  - Numerous data suggest that an increase of cancer stem cells (CSCs) in tumor mass
      can be the reason for failure of conventional therapies because of their
      resistance. CD44+/CD24- cells are a putative cancer stem cells subpopulation in
      prostate cancer. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)
      is an activator of apoptosis in tumor cells. However, some tumors are TRAIL
      resistant. Cancer cells can be re-sensitized to TRAIL induced apoptosis by a
      combination of TRAIL and taxanes. The aim of this work was to analyze the
      enhancement of the anticancer effect of TRAIL by paclitaxel, cabazitaxel and
      docetaxel in the whole population of PC3 and DU145 prostate cancer cells, but
      also in CD44+/CD24- prostate cancer stem cells. We examined the apoptotic effect
      of TRAIL and taxanes using flow cytometry and Annexin-V-PE staining. The co
      treatment with taxanes and TRAIL enhanced significantly the apoptosis in
      CD44+/CD24- cells only in PC3 cell line but not in DU145 cells. We discovered
      also that taxanes can increase the expression of death receptor TRAIL-R2 in PC3
      prostate cancer cells. The results of our study show that treatment with
      paclitaxel, cabazitaxel and docetaxel is able to enhance the apoptosis induced by
      TRAIL even in prostate cancer stem cells.

PMID- 28758909
TI  - Exogenous GR24 Alleviates Cadmium Toxicity by Reducing Cadmium Uptake in
      Switchgrass (Panicum virgatum) Seedlings.
AB  - Strigolactones (SLs) are classified into plant hormones, playing a key role as a
      mediator of plant growth in response to several abiotic stresses, including
      drought and salinity. However, the role of SLs in cadmium (Cd)-induced stress to
      plants is still unknown. The physiological responses of switchgrass (Panicum
      virgatum) stressed in 10 MUmol L-1 Cd to exogenous synthetic SLs analog, GR24
      were studied in hydroponics. The Cd stress significantly caused the adverse
      effects on plant growth and root morphology, inhibited photosynthesis, but
      boosted lipid peroxidation of Switchgrass seedlings. After treatment of 1 MUmol L
      1 GR24, the above adverse effects caused by Cd stress were significantly
      alleviated, mainly reflects in improvement of shoot biomass, relative water
      content, root development, chlorophyll contents, activities of typical
      antioxidant enzymes, nutrient uptake. The reason for exogenous GR24 alleviating
      cadmium toxicity might be owing to that exogenous GR24 promoted the content of
      endogenous SLs, increased some essential element Fe (iron), Zn (zinc), Mn
      (manganese) and Cu (copper) uptake and reduced cadmium uptake, accumulation and
      partition in shoot of switchgrass seedlings.

PMID- 28758906
TI  - Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in
      fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease
      characterized by extraskeletal bone formation through endochondral ossification.
      Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs.
      Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP
      signaling, we and others have uncovered a mechanism by which FOP-ACVR1
      mistransduces BMP signaling in response to Activin-A, a molecule that normally
      transduces TGF-beta signaling. Although Activin-A evokes enhanced chondrogenesis
      in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms
      have yet to be revealed. To this end, we developed a high-throughput screening
      (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs)
      to identify pivotal pathways in enhanced chondrogenesis that are initiated by
      Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR
      signaling as a critical pathway for the aberrant chondrogenesis of mesenchymal
      stromal cells derived from FOP-iPSCs (FOP-iMSCs). Two different HO mouse models,
      an FOP model mouse expressing FOP-ACVR1 and an FOP-iPSC-based HO model mouse,
      revealed critical roles for mTOR signaling in vivo. Moreover, we identified
      ENPP2, an enzyme that generates lysophosphatidic acid, as a linker of FOP-ACVR1
      and mTOR signaling in chondrogenesis. These results uncovered the crucial role of
      the Activin-A/FOP-ACVR1/ENPP2/mTOR axis in FOP pathogenesis.

PMID- 28758910
TI  - Development of a UPLC-MS/MS Method for Simultaneous Determination of Six
      Flavonoids in Rat Plasma after Administration of Maydis stigma Extract and Its
      Application to a Comparative Pharmacokinetic Study in Normal and Diabetic Rats.
AB  - Maydis stigma is an important medicine herb used in many parts of the world for
      treatment of diabetes mellitus, which main bioactive ingredients are flavonoids.
      This paper describes for the first time a study on the comparative
      pharmacokinetics of six active flavonoid ingredients of Maydis stigma in normal
      and diabetic rats orally administrated with the decoction. Therefore, an
      efficient and sensitive ultra high performance liquid chromatography coupled to
      tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination
      of six anti-diabetic ingredients (cynaroside, quercetin, luteolin, isorhamnetin,
      rutin and formononetin) of Maydis stigma in rat plasma has been developed and
      validated in plasma samples, which showed good linearity over a wide
      concentration range (r2 > 0.99), and gave a lower limit of quantification of 1.0
      ng.mL-1 for the analytes. The intra- and interday assay variability was less than
      15% for all analytes. The mean extraction recoveries and matrix effect of
      analytes and IS from rats plasma were all more than 85.0%. The stability results
      showed the measured concentration for six analytes at three QC levels deviated
      within 15.0%. The results indicated that significant differences in the
      pharmacokinetic parameters of the analytes were observed between the two groups
      of animals, whereby the absorptions of these analytes in the diabetic group were
      all significantly higher than those in the normal group, which provides an
      experimental basis for the role of Maydis stigma in anti-diabetic treatment.

PMID- 28758911
TI  - Molecular Cloning and Characterization of PnbHLH1 Transcription Factor in Panax
      notoginseng.
AB  - Panax notoginseng has been extensively used as a traditional Chinese medicine. In
      the current study, molecular cloning and characterization of PnbHLH1
      transcription factor were explored in Panax notoginseng. The full length of the
      PnbHLH1 gene obtained by splicing was 1430 bp, encoding 321 amino acids.
      Prokaryotic expression vector pET-28a-PnbHLH1 was constructed and transferred
      into the BL21 prokaryotic expression strain. An electrophoretic mobility shift
      assay of PnbHLH1 protein binding to E-box cis-acting elements verified that
      PnbHLH1 belonged to the bHLH class transcription factor which could interact with
      the promoter region of the E-box core sequence. The expression levels of key
      genes involved in the biosynthesis of triterpenoid saponins in PnbHLH1 transgenic
      cells were higher than those in the wild cells. Similarly, the total saponin
      contents were increased in the PnbHLH1 transgenic cell lines compared with the
      wild cell lines. Such results suggest that the PnbHLH1 transcription factor is a
      positive regulator in the biosynthesis of triterpenoid saponins in Panax
      notoginseng.

PMID- 28758912
TI  - Spectroscopic Characterization and Nanosafety of Ag-Modified Antibacterial
      Leather and Leatherette.
AB  - The development of antibacterial coatings is of great interest from both industry
      and the consumer's point of view. In this study, we characterized tanned leather
      and polyurethane leatherette, typically employed in the automotive and footwear
      industries, which were modified by photo-deposition of antibacterial silver
      nanoparticles (AgNPs). Material surface chemical composition was investigated in
      detail by X-ray photoelectron spectroscopy (XPS). The material's antibacterial
      capability was checked against Escherichia coli and Staphylococcus aureus, as
      representative microorganisms in cross transmissions. Due to the presence of
      silver in a nanostructured form, nanosafety issues were considered, as well.
      Ionic release in contact media, as well as whole nanoparticle release from
      treated materials, were quantitatively evaluated, thus providing specific
      information on potential product nanotoxicity, which was further investigated
      through cytocompatibility MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assays, also after surface abrasion of the
      materials. The proved negligible nanoparticle release, as well as the controlled
      release of antibacterial ions, shed light on the materials' potentialities, in
      terms of both high activity and safety.

PMID- 28758913
TI  - Versatility of Pyridoxal Phosphate as a Coating of Iron Oxide Nanoparticles.
AB  - Pyridoxal 5'-phosphate (PLP) is the most important cofactor of vitamin B6
      dependent enzymes, which catalyses a wide range of essential body functions
      (e.g., metabolism) that could be exploited to specifically target highly
      metabolic cells, such as tumour metastatic cells. However, the use of PLP as a
      simultaneous coating and targeting molecule, which at once provides colloidal
      stability and specific biological effects has not been exploited so far.
      Therefore, in this work iron oxide nanoparticles (IONPs) were coated by PLP at
      two different pH values to tune PLP bonding (e.g., orientation) at the IONP
      surface. The surface study, as well as calculations, confirmed different PLP
      bonding to the IONP surface at these two pH values. Moreover, the obtained PLP
      IONPs showed different zeta potential, hydrodynamic radius and agglomeration
      state, and consequently different uptake by two metastatic-prostate-cancer cell
      lines (LnCaP and PC3). In LnCaP cells, PLP modified the morphology of IONP
      containing intracellular vesicles, while in PC3 cells PLP impacted the amount of
      IONPs taken up by cells. Moreover, PLP-IONPs displayed high magnetic resonance
      imaging (MRI) r2 relaxivity and were not toxic for the two studied cell lines,
      rendering PLP promising for biomedical applications. We here report the use of
      PLP simultaneously as a coating and targeting molecule, directly bound to the
      IONP surface, with the additional high potential for MRI detection.

PMID- 28758914
TI  - In Vitro Evaluation of Sub-Lethal Concentrations of Plant-Derived Antifungal
      Compounds on FUSARIA Growth and Mycotoxin Production.
AB  - Phytopathogenic fungi can lead to significant cereal yield losses, also producing
      mycotoxins dangerous for human and animal health. The fungal control based on the
      use of synthetic fungicides can be complemented by "green" methods for crop
      protection, based on the use of natural products. In this frame, the antifungal
      activities of bergamot and lemon essential oils and of five natural compounds
      recurrent in essential oils (citronellal, citral, cinnamaldehyde, cuminaldehyde
      and limonene) have been evaluated against three species of mycotoxigenic fungi
      (Fusarium sporotrichioides, F. graminearum and F. langsethiae) responsible for
      Fusarium Head Blight in small-grain cereals. The natural products concentrations
      effective for reducing or inhibiting the in vitro fungal growth were determined
      for each fungal species and the following scale of potency was found:
      cinnamaldehyde > cuminaldehyde > citral > citronellal > bergamot oil > limonene >
      lemon oil. Moreover, the in vitro mycotoxin productions of the three Fusaria
      strains exposed to sub-lethal concentrations of the seven products was evaluated.
      The three fungal species showed variability in response to the treatments, both
      in terms of inhibition of mycelial growth and in terms of modulation of mycotoxin
      production that can be enhanced by sub-lethal concentrations of some natural
      products. This last finding must be taken into account in the frame of an open
      field application of some plant-derived fungicides.

PMID- 28758915
TI  - beta-Formyl- and beta-Vinylporphyrins: Magic Building Blocks for Novel Porphyrin
      Derivatives.
AB  - Porphyrins bearing formyl or vinyl groups have been explored as starting
      materials to prepare new compounds with adequate features for different
      applications. In this review it is discussed mainly synthetic strategies based on
      the reaction of meso-tetraarylporphyrins bearing those groups at beta-pyrrolic
      positions. The use of some of the obtained porphyrin derivatives for further
      transformations, namely via pericyclic reactions, is also highlighted.

PMID- 28758916
TI  - Effect of a Particulate and a Putty-Like Tricalcium Phosphate-Based Bone-grafting
      Material on Bone Formation, Volume Stability and Osteogenic Marker Expression
      after Bilateral Sinus Floor Augmentation in Humans.
AB  - This study examines the effect of a hyaluronic acid (HyAc) containing tricalcium
      phosphate putty scaffold material (TCP-P) and of a particulate tricalcium
      phosphate (TCP-G) graft on bone formation, volume stability and osteogenic marker
      expression in biopsies sampled 6 months after bilateral sinus floor augmentation
      (SFA) in 7 patients applying a split-mouth design. 10% autogenous bone chips were
      added to the grafting material during surgery. The grain size of the TCP granules
      was 700 to 1400 um for TCP-G and 125 to 250 um and 500 to 700 um (ratio 1:1) for
      TCP-P. Biopsies were processed for immunohistochemical analysis of resin-embedded
      sections. Sections were stained for collagen type I (Col I), alkaline phosphatase
      (ALP), osteocalcin (OC) and bone sialoprotein (BSP). Furthermore, the bone area
      and biomaterial area fraction were determined histomorphometrically. Cone-beam CT
      data recorded after SFA and 6 months later were used for calculating the graft
      volume at these two time points. TCP-P displayed more advantageous surgical
      handling properties and a significantly greater bone area fraction and smaller
      biomaterial area fraction. This was accompanied by significantly greater
      expression of Col I and BSP and in osteoblasts and osteoid and a less pronounced
      reduction in grafting volume with TCP-P. SFA using both types of materials
      resulted in formation of sufficient bone volume for facilitating stable dental
      implant placement with all dental implants having been in function without any
      complications for 6 years. Since TCP-P displayed superior surgical handling
      properties and greater bone formation than TCP-G, without the HyAc hydrogel
      matrix having any adverse effect on bone formation or graft volume stability, TCP
      P can be regarded as excellent grafting material for SFA in a clinical setting.
      The greater bone formation observed with TCP-P may be related to the difference
      in grain size of the TCP granules and/or the addition of the HyAc.

PMID- 28758917
TI  - Heat Exposure and Maternal Health in the Face of Climate Change.
AB  - Climate change will increasingly affect the health of vulnerable populations,
      including maternal and fetal health. This systematic review aims to identify
      recent literature that investigates increasing heat and extreme temperatures on
      pregnancy outcomes globally. We identify common research findings in order to
      create a comprehensive understanding of how immediate effects will be sustained
      in the next generation. Following the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) guide, we systematically reviewed articles
      from PubMed and Cochrane Reviews. We included articles that identify climate
      change-related exposures and adverse health effects for pregnant women. There is
      evidence that temperature extremes adversely impact birth outcomes, including,
      but not limited to: changes in length of gestation, birth weight, stillbirth, and
      neonatal stress in unusually hot temperature exposures. The studies included in
      this review indicate that not only is there a need for further research on the
      ways that climate change, and heat in particular, may affect maternal health and
      neonatal outcomes, but that uniform standards for assessing the effects of heat
      on maternal fetal health also need to be established.

PMID- 28758918
TI  - Rheological, Chemical and Physical Characteristics of Golden Berry (Physalis
      peruviana L.) after Convective and Microwave Drying.
AB  - Studies on methods for fixing foods (with a slight loss of bioactive compounds)
      and obtaining attractive products are important with respect to current
      technology. The drying process allows for a product with highly bioactive
      properties. Drying of Physalis fruit was carried out in a conventional manner,
      and in a microwave under reduced pressure at 120 W and 480 W. After drying, the
      fruits were subjected to strength and rheological tests. Water activity, content
      of carotenoids and polyphenols and antioxidant activity as well as colour were
      also examined. The study showed that Physalis is a difficult material for drying.
      The best results were obtained using microwave drying at a power of 480 W.
      Physalis fruit microwave-dried by this method is characterized by higher
      resistance to compression than the fruit dried by convection. Dried fruit
      obtained in this way was characterized by higher contents of bioactive compounds,
      better antioxidant properties, and at the same time the lowest water activity.

PMID- 28758919
TI  - Research Progress in the Modification of Quercetin Leading to Anticancer Agents.
AB  - The flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone) is widely distributed
      in plants, foods, and beverages. This polyphenol compound exhibits varied
      biological actions such as antioxidant, radical-scavenging, anti-inflammatory,
      antibacterial, antiviral, gastroprotective, immune-modulator, and finds also
      application in the treatment of obesity, cardiovascular diseases and diabetes.
      Besides, quercetin can prevent neurological disorders and exerts protection
      against mitochondrial damages. Various in vitro studies have assessed the
      anticancer effects of quercetin, although there are no conclusive data regarding
      its mode of action. However, low bioavailability, poor aqueous solubility as well
      as rapid body clearance, fast metabolism and enzymatic degradation hamper the use
      of quercetin as therapeutic agent, so intense research efforts have been focused
      on the modification of the quercetin scaffold to obtain analogs with potentially
      improved properties for clinical applications. This review gives an overview of
      the developments in the synthesis and anticancer-related activities of quercetin
      derivatives reported from 2012 to 2016.

PMID- 28758920
TI  - A Single Day of Excessive Dietary Fat Intake Reduces Whole-Body Insulin
      Sensitivity: The Metabolic Consequence of Binge Eating.
AB  - Consuming excessive amounts of energy as dietary fat for several days or weeks
      can impair glycemic control and reduce insulin sensitivity in healthy adults.
      However, individuals who demonstrate binge eating behavior overconsume for much
      shorter periods of time; the metabolic consequences of such behavior remain
      unknown. The aim of this study was to determine the effect of a single day of
      high-fat overfeeding on whole-body insulin sensitivity. Fifteen young, healthy
      adults underwent an oral glucose tolerance test before and after consuming a high
      fat (68% of total energy), high-energy (78% greater than daily requirements) diet
      for one day. Fasting and postprandial plasma concentrations of glucose, insulin,
      non-esterified fatty acids, and triglyceride were measured and the Matsuda
      insulin sensitivity index was calculated. One day of high-fat overfeeding
      increased postprandial glucose area under the curve (AUC) by 17.1% (p < 0.0001)
      and insulin AUC by 16.4% (p = 0.007). Whole-body insulin sensitivity decreased by
      28% (p = 0.001). In conclusion, a single day of high-fat, overfeeding impaired
      whole-body insulin sensitivity in young, healthy adults. This highlights the
      rapidity with which excessive consumption of calories through high-fat food can
      impair glucose metabolism, and suggests that acute binge eating may have
      immediate metabolic health consequences for the individual.

PMID- 28758921
TI  - Nitrogenous Derivatives of Phosphorus and the Origins of Life: Plausible
      Prebiotic Phosphorylating Agents in Water.
AB  - Phosphorylation under plausible prebiotic conditions continues to be one of the
      defining issues for the role of phosphorus in the origins of life processes. In
      this review, we cover the reactions of alternative forms of phosphate,
      specifically the nitrogenous versions of phosphate (and other forms of reduced
      phosphorus species) from a prebiotic, synthetic organic and biochemistry
      perspective. The ease with which such amidophosphates or phosphoramidate
      derivatives phosphorylate a wide variety of substrates suggests that alternative
      forms of phosphate could have played a role in overcoming the "phosphorylation in
      water problem". We submit that serious consideration should be given to the
      search for primordial sources of nitrogenous versions of phosphate and other
      versions of phosphorus.

PMID- 28758922
TI  - Kinetics and Energetics of Thermal Cis-Trans Isomerization of a Resonance
      Activated Azobenzene in BMIM-Based Ionic Liquids for PF6-/Tf2N- Comparison.
AB  - BMIM PF6 (1-butyl-3-methylimidazolium hexafluorophosphate) and BMIM Tf2N (1-butyl
      3-methylimidazolium bis(trifluoromethylsulfonyl)imide) are two conventional room
      temperature ionic liquids widely employed and investigated as reaction media.
      Despite the presence of the same imidazolium ring in their structure they are
      different in many chemical and physical properties due to the nature of the
      anions. The thermal cis-trans isomerization of an electronically activated
      azobenzene have been used as reaction model to compare the behavior of PF6- and
      Tf2N-. Rotation is the mechanism by which the investigated azobenzene is
      converted into the trans isomer spontaneously in the dark both in BMIM PF6 and in
      BMIM Tf2N. The kinetic rate constants of the process have been determined at
      different temperatures and the activation energies of the reaction have been
      calculated according to the Arrhenius and Eyring equations. The results presented
      herein highlight different solute-solvent interactions involving the PF6- and
      Tf2N- anions during the cis-trans isomerization.

PMID- 28758923
TI  - Sublethal Effects in Pest Management: A Surrogate Species Perspective on Fruit
      Fly Control.
AB  - Tephritid fruit flies are economically important orchard pests globally. While
      much effort has focused on controlling individual species with a combination of
      pesticides and biological control, less attention has been paid to managing
      assemblages of species. Although several tephritid species may co-occur in
      orchards/cultivated areas, especially in mixed-cropping schemes, their responses
      to pesticides may be highly variable. Furthermore, predictive efforts about
      toxicant effects are generally based on acute toxicity, with little or no regard
      to long-term population effects. Using a simple matrix model parameterized with
      life history data, we quantified the responses of several tephritid species to
      the sublethal effects of a toxicant acting on fecundity. Using a critical
      threshold to determine levels of fecundity reduction below which species are
      driven to local extinction, we determined that threshold levels vary widely for
      the three tephritid species. In particular, Bactrocera dorsalis was the most
      robust of the three species, followed by Ceratitis capitata, and then B.
      cucurbitae, suggesting individual species responses should be taken into account
      when planning for area-wide pest control. The rank-order of susceptibility
      contrasts with results from several field/lab studies testing the same species,
      suggesting that considering a combination of life history traits and individual
      species susceptibility is necessary for understanding population responses of
      species assemblages to toxicant exposure.

PMID- 28758924
TI  - Unusual Onset of Celiac Disease and Addison's Disease in a 12-Year-Old Boy.
AB  - BACKGROUND: Celiac disease (CD) is an autoimmune disorder deriving from an
      aberrant adaptive immune response against gluten-containing grains in genetically
      predisposed subjects. In a number of patients, CD is associated with one or more
      other autoimmune diseases. Primary Addison's disease (AD) and CD may co-exist,
      although this association is relatively uncommon in children. In addition, it is
      not precisely defined whether a gluten-free diet influences the course of AD.
      CASE PRESENTATION: A case of CD in a 12-year-old boy presenting as acute adrenal
      insufficiency is described here. A gluten-free diet had a significant therapeutic
      role in this case, wherein most of the clinical signs and symptoms of AD
      disappeared in a few days. In addition, the dosage of cortisol acetate, initially
      administered to treat the AD, was able to be rapidly reduced. CONCLUSION: This
      case highlights that CD can be associated with AD in children, and a gluten-free
      diet seems to positively influence the course of AD.

PMID- 28758925
TI  - Analysis of the Masked Metabolite of Deoxynivalenol and Fusarium Resistance in
      CIMMYT Wheat Germplasm.
AB  - Fusarium head blight (FHB) causes significant grain loss and contamination of
      grains with harmful mycotoxins, especially deoxynivalenol (DON). Fusarium
      resistance and DON accumulation have been extensively investigated in various
      cultivars; however, the level of DON-3-O-glucoside (D3G) has not been as
      carefully studied. In this study, we measured accumulated DON and D3G levels in
      CIMMYT wheat elite germplasm using an analytical method validated in-house. Co
      occurring nivalenol (NIV) and ergostrerol (ERG) were also analyzed. LC-MS/MS and
      LC-UV analyses were applied to the 50 CIMMYT elite wheat lines. D3G showed rather
      high correlation with DON (r = 0.82), while FHB symptoms showed slight
      correlation with DON and D3G (r = 0.36 and 0.32, respectively). D3G/DON ratio
      varied widely from 8.1 to 37.7%, and the ratio was not related with FHB
      resistance in this dataset.

PMID- 28758926
TI  - EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang
      Equilibrium Recapitulated in Cell Spheroids.
AB  - The epithelial-to-mesenchymal transition (EMT) is an essential trans
      differentiation process, which plays a critical role in embryonic development,
      wound healing, tissue regeneration, organ fibrosis, and cancer progression. It is
      the fundamental mechanism by which epithelial cells lose many of their
      characteristics while acquiring features typical of mesenchymal cells, such as
      migratory capacity and invasiveness. Depending on the contest, EMT is
      complemented and balanced by the reverse process, the mesenchymal-to-epithelial
      transition (MET). In the saving economy of the living organisms, the same (Ying
      Yang) tool is integrated as a physiological strategy in embryonic development, as
      well as in the course of reparative or disease processes, prominently fibrosis,
      tumor invasion and metastasis. These mechanisms and their related signaling
      (e.g., TGF-beta and BMPs) have been effectively studied in vitro by tissue
      derived cell spheroids models. These three-dimensional (3D) cell culture systems,
      whose phenotype has been shown to be strongly dependent on TGF-beta-regulated
      EMT/MET processes, present the advantage of recapitulating in vitro the hypoxic
      in vivo micro-environment of tissue stem cell niches and their formation. These
      spheroids, therefore, nicely reproduce the finely regulated Ying-Yang
      equilibrium, which, together with other mechanisms, can be determinant in cell
      fate decisions in many pathophysiological scenarios, such as differentiation,
      fibrosis, regeneration, and oncogenesis. In this review, current progress in the
      knowledge of signaling pathways affecting EMT/MET and stemness regulation will be
      outlined by comparing data obtained from cellular spheroids systems, as ex vivo
      niches of stem cells derived from normal and tumoral tissues. The mechanistic
      correspondence in vivo and the possible pharmacological perspective will be also
      explored, focusing especially on the TGF-beta-related networks, as well as
      others, such as SNAI1, PTEN, and EGR1. This latter, in particular, for its
      ability to convey multiple types of stimuli into relevant changes of the cell
      transcriptional program, can be regarded as a heterogeneous "stress-sensor" for
      EMT-related inducers (growth factor, hypoxia, mechano-stress), and thus as a
      therapeutic target.

PMID- 28758927
TI  - Transcriptome Profiling in Human Diseases: New Advances and Perspectives.
AB  - In the last decades, transcriptome profiling has been one of the most utilized
      approaches to investigate human diseases at the molecular level. Through
      expression studies, many molecular biomarkers and therapeutic targets have been
      found for several human pathologies. This number is continuously increasing
      thanks to total RNA sequencing. Indeed, this new technology has completely
      revolutionized transcriptome analysis allowing the quantification of gene
      expression levels and allele-specific expression in a single experiment, as well
      as to identify novel genes, splice isoforms, fusion transcripts, and to
      investigate the world of non-coding RNA at an unprecedented level. RNA sequencing
      has also been employed in important projects, like ENCODE (Encyclopedia of the
      regulatory elements) and TCGA (The Cancer Genome Atlas), to provide a snapshot of
      the transcriptome of dozens of cell lines and thousands of primary tumor
      specimens. Moreover, these studies have also paved the way to the development of
      data integration approaches in order to facilitate management and analysis of
      data and to identify novel disease markers and molecular targets to use in the
      clinics. In this scenario, several ongoing clinical trials utilize transcriptome
      profiling through RNA sequencing strategies as an important instrument in the
      diagnosis of numerous human pathologies.

PMID- 28758928
TI  - Role of Plasminogen Activator Inhibitor Type 1 in Pathologies of Female
      Reproductive Diseases.
AB  - Normal pregnancy is a state of hypercoagulability with diminishing fibrinolytic
      activity, which is mainly caused by an increase of plasminogen activator
      inhibitor type 1 (PAI-1). PAI-1 is the main inhibitor of plasminogen activators,
      including tissue-type plasminogen activator (tPA) and urokinase-type plasminogen
      activator (uPA). In human placentas, PAI-1 is expressed in extravillous
      interstitial trophoblasts and vascular trophoblasts. During implantation and
      placentation, PAI-1 is responsible for inhibiting extra cellular matrix (ECM)
      degradation, thereby causing an inhibition of trophoblasts invasion. In the
      present study, we have reviewed the literature of various reproductive diseases
      where PAI-1 plays a role. PAI-1 levels are increased in patients with recurrent
      pregnancy losses (RPL), preeclampsia, intrauterine growth restriction (IUGR),
      gestational diabetes mellitus (GDM) in the previous pregnancy, endometriosis and
      polycystic ovary syndrome (PCOS). In general, an increased expression of PAI-1 in
      the blood is associated with an increased risk for infertility and a worse
      pregnancy outcome. GDM and PCOS are related to the genetic role of the 4G/5G
      polymorphism of PAI-1. This review provides an overview of the current knowledge
      of the role of PAI-1 in reproductive diseases. PAI-1 represents a promising
      monitoring biomarker for reproductive diseases and may be a treatment target in
      the near future.

PMID- 28758929
TI  - Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions.
AB  - Accumulating evidence links obesity with low-grade inflammation which may
      originate from adipose tissue that secretes a plethora of pro- and anti
      inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as
      crucial signals in many obesity-related pathologies including non-alcoholic fatty
      liver disease (NAFLD). Whereas adiponectin deficiency might be critically
      involved in the pro-inflammatory state associated with obesity and related
      disorders, overproduction of leptin, a rather pro-inflammatory mediator, is
      considered of equal relevance. An imbalanced adipokine profile in obesity
      consecutively contributes to metabolic inflammation in NAFLD, which is associated
      with a substantial risk for developing hepatocellular carcinoma (HCC) also in the
      non-cirrhotic stage of disease. Both adiponectin and leptin have been related to
      liver tumorigenesis especially in preclinical models. This review covers recent
      advances in our understanding of some adipokines in NAFLD and associated HCC.

PMID- 28758930
TI  - Treatment of Human Placental Choriocarcinoma Cells with Formaldehyde and Benzene
      Induced Growth and Epithelial Mesenchymal Transition via Induction of an
      Antioxidant Effect.
AB  - Cigarette smoke (CS) causes about 480,000 deaths each year worldwide, and it is
      well-known to have harmful effects on the human body, leading to heart disease,
      stroke, lung cancer, and cardiovascular problems. In this study, the effects of
      formaldehyde (FA) and benzene (Bz), the main components of CS, on cell
      proliferation and epithelial mesenchymal transition (EMT) of JEG-3 human
      choriocarcinoma cells were examined to confirm the relationship between CS
      components and placenta carcinoma. Upon MTT assay, FA (10-8 M to 10-5 M) and Bz
      (10-11 M to 10-8 M) increased JEG-3 cell proliferation. Western blot assay
      revealed that the protein expression of cyclin D1 and E1 increased, while the
      levels of p21 and p27 were reduced following treatment. In Scratch assay, FA (10
      8 M and 10-5 M) and Bz (10-11 M and 10-8 M) increased migration of JEG-3 cells at
      24 h and 48 h compared with that at 0 h. In addition, the expression of the
      epithelial marker, E-cadherin, was significantly decreased, while the expression
      of the mesenchymal marker, N-cadherin, was significantly increased by FA (10-8 M
      and 10-5 M) and Bz (10-11 M and 10-8 M). snail and slug transcriptional factors
      were associated with EMT, which were also up-regulated by FA and Bz, indicating
      that FA and Bz lead to an increase in the EMT process in JEG-3 choriocarcinoma
      cells. We further evaluated reactive oxygen species (ROS) and activation of
      antioxidant effect using dichlorofluorescin diacetate (DCFH-DA) and Western blot
      assay. FA and Bz increased the ROS production and an antioxidant related marker,
      Nrf2, in JEG-3 cells. However, eIF2alpha levels were reduced by FA and Bz via
      activation of the antioxidant reaction. Taken together, these results indicated
      that FA and Bz induce the growth and migration of human choriocarcinoma cells via
      regulation of the cell cycle and EMT and activation of ROS and antioxidant
      related markers.

PMID- 28758932
TI  - Nanometric Integrated Temperature and Thermal Sensors in CMOS-SOI Technology.
AB  - This paper reviews and compares the thermal and noise characterization of CMOS
      (complementary metal-oxide-semiconductor) SOI (Silicon on insulator) transistors
      and lateral diodes used as temperature and thermal sensors. DC analysis of the
      measured sensors and the experimental results in a broad (300 K up to 550 K)
      temperature range are presented. It is shown that both sensors require small chip
      area, have low power consumption, and exhibit linearity and high sensitivity over
      the entire temperature range. However, the diode's sensitivity to temperature
      variations in CMOS-SOI technology is highly dependent on the diode's perimeter;
      hence, a careful calibration for each fabrication process is needed. In contrast,
      the short thermal time constant of the electrons in the transistor's channel
      enables measuring the instantaneous heating of the channel and to determine the
      local true temperature of the transistor. This allows accurate "on-line"
      temperature sensing while no additional calibration is needed. In addition, the
      noise measurements indicate that the diode's small area and perimeter causes a
      high 1/f noise in all measured bias currents. This is a severe drawback for the
      sensor accuracy when using the sensor as a thermal sensor; hence, CMOS-SOI
      transistors are a better choice for temperature sensing.

PMID- 28758931
TI  - Tumor-Stroma Crosstalk in Bone Tissue: The Osteoclastogenic Potential of a Breast
      Cancer Cell Line in a Co-Culture System and the Role of EGFR Inhibition.
AB  - Although bone metastases represent a major challenge in the natural history of
      breast cancer (BC), the complex interactions involved have hindered the
      development of robust in vitro models. The aim of this work is the development of
      a preclinical model of cancer and bone stromal cells to mimic the bone
      microenvironment. We studied the effects on osteoclastogenesis of BC cells and
      Mesenchymal stem cells (MSC) cultured alone or in combination. We also analyzed:
      (a) whether the blockade of the Epithelial Growth Factor Receptor (EGFR) pathway
      modified their influence on monocytes towards differentiation, and (b) the
      efficacy of bone-targeted therapy on osteoclasts. We evaluated the
      osteoclastogenesis modulation of human peripheral blood monocytes (PBMC)
      indirectly induced by the conditioned medium (CM) of the human BC cell line SCP2,
      cultured singly or with MSC. Osteoclastogenesis was evaluated by TRAP analysis.
      The effect of the EGFR blockade was assessed by treating the cells with
      gefitinib, and analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and Western Blot (WB). We observed that
      SCP2 co-cultured with MSC increased the differentiation of PBMC. This effect was
      underpinned upon pre-treatment of the co-culture with gefitinib. Co-culture of
      SCP2 with MSC increased the expression of both the bone-related marker Receptor
      Activator of Nuclear Factor kappaB (RANK) and EGFR in BC cells. These
      upregulations were not affected by the EGFR blockade. The effects of the CM
      obtained by the cells treated with gefitinib in combination with the treatment of
      the preosteoclasts with the bone-targeted agents and everolimus enhanced the
      inhibition of the osteoclastogenesis. Finally, we developed a fully human co
      culture system of BC cells and bone progenitor cells. We observed that the
      interaction of MSC with cancer cells induced in the latter molecular changes and
      a higher power of inducing osteoclastogenesis. We found that blocking EGFR
      signaling could be an efficacious strategy for breaking the interactions between
      cancer and bone cells in order to inhibit bone metastasis.

PMID- 28758933
TI  - Flexible Mixed-Potential-Type (MPT) NO2 Sensor Based on An Ultra-Thin Ceramic
      Film.
AB  - A novel flexible mixed-potential-type (MPT) sensor was designed and fabricated
      for NO2 detection from 0 to 500 ppm at 200  degrees C. An ultra-thin Y2O3-doped
      ZrO2 (YSZ) ceramic film 20 um thick was sandwiched between a heating electrode
      and reference/sensing electrodes. The heating electrode was fabricated by a
      conventional lift-off process, while the porous reference and the sensing
      electrodes were fabricated by a two-step patterning method using shadow masks.
      The sensor's sensitivity is achieved as 58.4 mV/decade at the working temperature
      of 200  degrees C, as well as a detection limit of 26.7 ppm and small response
      time of less than 10 s at 200 ppm. Additionally, the flexible MPT sensor
      demonstrates superior mechanical stability after bending over 50 times due to the
      mechanical stability of the YSZ ceramic film. This simply structured, but highly
      reliable flexible MPT NO2 sensor may lead to wide application in the automobile
      industry for vehicle emission systems to reduce NO2 emissions and improve fuel
      efficiency.

PMID- 28758934
TI  - Simultaneous Indoor Tracking and Activity Recognition Using Pyroelectric Infrared
      Sensors.
AB  - Indoor human tracking and activity recognition are fundamental yet coherent
      problems for ambient assistive living. In this paper, we propose a method to
      address these two critical issues simultaneously. We construct a wireless sensor
      network (WSN), and the sensor nodes within WSN consist of pyroelectric infrared
      (PIR) sensor arrays. To capture the tempo-spatial information of the human
      target, the field of view (FOV) of each PIR sensor is modulated by masks. A
      modified partial filter algorithm is utilized to decode the location of the human
      target. To exploit the synergy between the location and activity, we design a two
      layer random forest (RF) classifier. The initial activity recognition result of
      the first layer is refined by the second layer RF by incorporating various
      effective features. We conducted experiments in a mock apartment. The mean
      localization error of our system is about 0.85 m. For five kinds of daily
      activities, the mean accuracy for 10-fold cross-validation is above 92%. The
      encouraging results indicate the effectiveness of our system.

PMID- 28758935
TI  - A Solar Position Sensor Based on Image Vision.
AB  - Solar collector technologies operate with better performance when the Sun beam
      direction is normal to the capturing surface, and for that to happen despite the
      relative movement of the Sun, solar tracking systems are used, therefore, there
      are rules and standards that need minimum accuracy for these tracking systems to
      be used in solar collectors' evaluation. Obtaining accuracy is not an easy job,
      hence in this document the design, construction and characterization of a sensor
      based on a visual system that finds the relative azimuth error and height of the
      solar surface of interest, is presented. With these characteristics, the sensor
      can be used as a reference in control systems and their evaluation. The proposed
      sensor is based on a microcontroller with a real-time clock, inertial measurement
      sensors, geolocation and a vision sensor, that obtains the angle of incidence
      from the sunrays' direction as well as the tilt and sensor position. The sensor's
      characterization proved how a measurement of a focus error or a Sun position can
      be made, with an accuracy of 0.0426 degrees  and an uncertainty of 0.986%, which
      can be modified to reach an accuracy under 0.01 degrees . The validation of this
      sensor was determined showing the focus error on one of the best commercial solar
      tracking systems, a Kipp & Zonen SOLYS 2. To conclude, the solar tracking sensor
      based on a vision system meets the Sun detection requirements and components that
      meet the accuracy conditions to be used in solar tracking systems and their
      evaluation or, as a tracking and orientation tool, on photovoltaic installations
      and solar collectors.

PMID- 28758936
TI  - Position, Orientation and Velocity Detection of Unmanned Underwater Vehicles
      (UUVs) Using an Optical Detector Array.
AB  - This paper presents a proof-of-concept optical detector array sensor system to be
      used in Unmanned Underwater Vehicle (UUV) navigation. The performance of the
      developed optical detector array was evaluated for its capability to estimate the
      position, orientation and forward velocity of UUVs with respect to a light source
      fixed in underwater. The evaluations were conducted through Monte Carlo
      simulations and empirical tests under a variety of motion configurations. Monte
      Carlo simulations also evaluated the system total propagated uncertainty (TPU) by
      taking into account variations in the water column turbidity, temperature and
      hardware noise that may degrade the system performance. Empirical tests were
      conducted to estimate UUV position and velocity during its navigation to a light
      beacon. Monte Carlo simulation and empirical results support the use of the
      detector array system for optics based position feedback for UUV positioning
      applications.

PMID- 28758937
TI  - A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients
      with Severe Lung Disease.
AB  - In recent years, next-generation sequencing (NGS) was employed to decipher the
      structure and composition of the microbiota of the airways in cystic fibrosis
      (CF) patients. However, little is still known about the overall gene functions
      harbored by the resident microbial populations and which specific genes are
      associated with various stages of CF lung disease. In the present study, we aimed
      to identify the microbial gene repertoire of CF microbiota in twelve patients
      with severe and normal/mild lung disease by performing sputum shotgun metagenome
      sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF
      airways was reconstructed from the metagenome. We identified a set of metabolic
      pathways differently distributed in patients with different pulmonary function;
      namely, pathways related to bacterial chemotaxis and flagellar assembly, as well
      as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence
      related genes. The results indicated that the microbiome of CF patients with low
      pulmonary function is enriched in virulence-related genes and in genes encoding
      efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of
      severely affected adults with CF seems to encode different mechanisms for the
      facilitation of microbial colonization and persistence in the lung, consistent
      with the characteristics of multidrug-resistant microbial communities that are
      commonly observed in patients with severe lung disease.

PMID- 28758938
TI  - Effects of Pomegranate Juice Supplementation on Oxidative Stress Biomarkers
      Following Weightlifting Exercise.
AB  - The aim of this study was to test the hypothesis that pomegranate juice
      supplementation would blunt acute and delayed oxidative stress responses after a
      weightlifting training session. Nine elite weightlifters (21.0 +/- 1 years)
      performed two Olympic-Weightlifting sessions after ingesting either the placebo
      or pomegranate juice supplements. Venous blood samples were collected at rest and
      3 min and 48 h after each session. Compared to the placebo condition, pomegranate
      juice supplementation attenuated the increase in malondialdehyde (-12.5%; p <
      0.01) and enhanced the enzymatic (+8.6% for catalase and +6.8% for glutathione
      peroxidase; p < 0.05) and non-enzymatic (+12.6% for uric acid and +5.7% for total
      bilirubin; p < 0.01) antioxidant responses shortly (3 min) after completion of
      the training session. Additionally, during the 48 h recovery period, pomegranate
      juice supplementation accelerated (p < 0.05) the recovery kinetics of the
      malondialdehyde (5.6%) and the enzymatic antioxidant defenses compared to the
      placebo condition (9 to 10%). In conclusion, supplementation with pomegranate
      juice has the potential to attenuate oxidative stress by enhancing antioxidant
      responses assessed acutely and up to 48 h following an intensive weightlifting
      training session. Therefore, elite weightlifters might benefit from blunted
      oxidative stress responses following intensive weightlifting sessions, which
      could have implications for recovery between training sessions.

PMID- 28758939
TI  - Stonin 2 Overexpression is Correlated with Unfavorable Prognosis and Tumor
      Invasion in Epithelial Ovarian Cancer.
AB  - Stonin 2 (STON2), which functions in adjusting endocytotic complexes, is probably
      involved in the monitoring of the internalization of dopamine D2 receptors which
      have an inhibitory action of dopamine on tumor progression. However, its clinical
      significance in tumor progression and prognosis remains unclear. We explored the
      association between STON2 and the clinicopathological characteristics of
      epithelial ovarian cancer (EOC). The STON2 levels in ovarian cancer and normal
      cell lines and tissues were detected by real-time PCR and Western blot analyses.
      STON2 protein expression was also detected by an immunohistochemical analysis.
      The clinical significance of STON2 expression in ovarian cancer was statistically
      analyzed. STON2 significantly increased in the ovarian cancer cell lines and
      tissues compared to the normal ones. In the 89 EOC samples tested, STON2
      expression was significantly correlated with intraperitoneal metastasis,
      intestinal metastasis, intraperitoneal recurrence, ascites containing tumor
      cells, and CA153 level. Moreover, patients with STON2 protein overexpression were
      more likely to exhibit platinum resistance and to have undergone neoadjuvant
      chemotherapy. Patients with high STON2 protein expression had a tendency to have
      a shorter overall survival and a poor prognosis. A multivariate analysis showed
      that STON2 was an independent prognostic predictor for EOC patients. In
      conclusion, STON2 plays an important role in the progression and prognosis of
      ovarian carcinoma, especially in platinum resistance, intraperitoneal metastasis,
      and recurrence. STON2 can be a novel antitumor drug target and biomarker which
      predicts an unfavorable prognosis for EOC patients.

PMID- 28758940
TI  - Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy
      Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and
      Elevations in Glutamic and Oleic Acid In Vivo.
AB  - BACKGROUND: Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular
      Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis,
      progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This
      severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as
      compared to unaffected normal dogs, while the long digital extensor (LDE), which
      functions to flex the tibiotarsal joint and serves as a digital extensor,
      undergoes the most pronounced atrophy. A recent microarray analysis of GRMD
      identified alterations in genes associated with lipid metabolism and energy
      production. METHODS: We, therefore, undertook a non-targeted metabolomics
      analysis of the milder/earlier stage disease GRMD BF muscle versus the more
      severe/chronic LDE using GC-MS to identify underlying metabolic defects specific
      for affected GRMD skeletal muscle. RESULTS: Untargeted metabolomics analysis of
      moderately-affected GRMD muscle (BF) identified eight significantly altered
      metabolites, including significantly decreased stearamide (0.23-fold of controls,
      p = 2.89 * 10-3), carnosine (0.40-fold of controls, p = 1.88 * 10-2), fumaric
      acid (0.40-fold of controls, p = 7.40 * 10-4), lactamide (0.33-fold of controls,
      p = 4.84 * 10-2), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 * 10
      2), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 * 10
      2), glutamic acid (2.48-fold of controls, p = 2.63 * 10-2), and proline (1.73
      fold of controls, p = 3.01 * 10-2). Pathway enrichment analysis identified
      significant enrichment for arginine/proline metabolism (p = 5.88 * 10-4, FDR 4.7
      * 10-2), where alterations in L-glutamic acid, proline, and carnosine were found.
      Additionally, multiple Krebs cycle intermediates were significantly decreased
      (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid),
      suggesting that altered energy metabolism may be underlying the observed GRMD BF
      muscle dysfunction. In contrast, two pathways, inosine-5'-monophosphate (VIP
      Score 3.91) and 3-phosphoglyceric acid (VIP Score 3.08) mainly contributed to the
      LDE signature, with two metabolites (phosphoglyceric acid and inosine-5'
      monophosphate) being significantly decreased. When the BF and LDE were compared, 
      the most significant metabolite was phosphoric acid, which was significantly less
      in the GRMD BF compared to control and GRMD LDE groups. CONCLUSIONS: The
      identification of elevated BF oleic acid (a long-chain fatty acid) is consistent
      with recent microarray studies identifying altered lipid metabolism genes, while
      alterations in arginine and proline metabolism are consistent with recent studies
      identifying elevated L-arginine in DMD patient sera as a biomarker of disease.
      Together, these studies demonstrate muscle-specific alterations in GRMD-affected
      muscle, which illustrate previously unidentified metabolic changes.

PMID- 28758941
TI  - Quick Estimation Model for the Concentration of Indoor Airborne Culturable
      Bacteria: An Application of Machine Learning.
AB  - Indoor airborne culturable bacteria are sometimes harmful to human health.
      Therefore, a quick estimation of their concentration is particularly necessary.
      However, measuring the indoor microorganism concentration (e.g., bacteria)
      usually requires a large amount of time, economic cost, and manpower. In this
      paper, we aim to provide a quick solution: using knowledge-based machine learning
      to provide quick estimation of the concentration of indoor airborne culturable
      bacteria only with the inputs of several measurable indoor environmental
      indicators, including: indoor particulate matter (PM2.5 and PM10), temperature,
      relative humidity, and CO2 concentration. Our results show that a general
      regression neural network (GRNN) model can sufficiently provide a quick and
      decent estimation based on the model training and testing using an experimental
      database with 249 data groups.

PMID- 28758942
TI  - Child Supervision and Burn Outcome among Admitted Patients at Major Trauma
      Hospitals in the Gambia.
AB  - Burn-related injuries are a significant burden in children, particularly in low-
      and middle-income countries (LMICs), where more than 90% of burn-related
      pediatric deaths occur. Lack of adult supervision of children is a major risk for
      pediatric burn injuries. The goal of this paper was to examine the general
      characteristics of burns and identify burn injury outcomes among adult-supervised
      children compared to those who were not supervised. The study examined burn
      injury and clinical characteristics among all burn patients admitted to two
      trauma hospitals in The Gambia, West Africa. At intake in the emergency room, the
      treating physician or nurse determined the need for admission based on body
      surface area burned (BSAB), depth of burn, and other clinical considerations such
      as co-occurring injuries and co-morbidities. During the study period of 1 April
      2014 through 31 October 2016, 105 burn patients were admitted and data were
      collected by the treating physician for all of them. Information about
      supervision was only asked for children aged five years or less. More than half
      (51%) of the burn patients were children under 18 years, and 22% were under 5
      years. Among children under five, most (86.4%) were supervised by an adult at the
      time of burn event. Of the 19 supervised children, 16 (84.2%) had body area
      surface burned (BSAB) of less than 20%. Two of the three children without adult
      supervision at the time of burn event had BSAB >= 20%. Overall, 59% of the
      patients had 20% + BSAB. Females (aOR = 1.25; 95% CI = 0.43-3.62), those burned
      in rural towns and villages (aOR = 2.29; 95% CI = 0.69-7.57), or burned by fire
      or flames (aOR = 1.47; 95% CI = 0.51-4.23) had increased odds of having a BSAB >=
      20%, although these differences were not statistically significant. Children 0-5
      years or 5-18 years (aOR = 0.04, 95% CI = 0.01-0.17; aOR = 0.07, 95% CI = 0.02
      0.23, respectively) were less likely to have BSAB >= 20% than adults. Those
      burned in a rural location (aOR = 9.23, 95% CI = 2.30-37.12) or by fire or flames
      (aOR = 6.09, 95% CI = 1.55-23.97) were more likely to die. Children 0-5 years or
      5-18 years (aOR = 0.2, 95% CI = 0.03-1.18; aOR = 0.38; 95% CI = 0.11-1.570,
      respectively) were less likely to die. Children constitute a significant
      proportion of admitted burn patients, and most of them were supervised at the
      time of the burn event. Supervised children (compared to unsupervised children)
      had less severe burns. Programs that focus on burn prevention at all levels
      including child supervision could increase awareness and reduce burns or their
      severity. Programs need to be designed and evaluated with focus on the child
      development stage and the leading causes of burns by age group.

PMID- 28758943
TI  - Crowd Sensing-Enabling Security Service Recommendation for Social Fog Computing
      Systems.
AB  - Fog computing, shifting intelligence and resources from the remote cloud to edge
      networks, has the potential of providing low-latency for the communication from
      sensing data sources to users. For the objects from the Internet of Things (IoT)
      to the cloud, it is a new trend that the objects establish social-like
      relationships with each other, which efficiently brings the benefits of developed
      sociality to a complex environment. As fog service become more sophisticated, it
      will become more convenient for fog users to share their own services, resources,
      and data via social networks. Meanwhile, the efficient social organization can
      enable more flexible, secure, and collaborative networking. Aforementioned
      advantages make the social network a potential architecture for fog computing
      systems. In this paper, we design an architecture for social fog computing, in
      which the services of fog are provisioned based on "friend" relationships. To the
      best of our knowledge, this is the first attempt at an organized fog computing
      system-based social model. Meanwhile, social networking enhances the complexity
      and security risks of fog computing services, creating difficulties of security
      service recommendations in social fog computing. To address this, we propose a
      novel crowd sensing-enabling security service provisioning method to recommend
      security services accurately in social fog computing systems. Simulation results
      show the feasibilities and efficiency of the crowd sensing-enabling security
      service recommendation method for social fog computing systems.

PMID- 28758945
TI  - Olive Actual "on Year" Yield Forecast Tool Based on the Tree Canopy Geometry
      Using UAS Imagery.
AB  - Olive has a notable importance in countries of Mediterranean basin and its
      profitability depends on several factors such as actual yield, production cost or
      product price. Actual "on year" Yield (AY) is production (kg tree-1) in "on
      years", and this research attempts to relate it with geometrical parameters of
      the tree canopy. Regression equation to forecast AY based on manual canopy volume
      was determined based on data acquired from different orchard categories and
      cultivars during different harvesting seasons in southern Spain. Orthoimages were
      acquired with unmanned aerial systems (UAS) imagery calculating individual crown
      for relating to canopy volume and AY. Yield levels did not vary between orchard
      categories; however, it did between irrigated orchards (7000-17,000 kg ha-1) and
      rainfed ones (4000-7000 kg ha-1). After that, manual canopy volume was related
      with the individual crown area of trees that were calculated by orthoimages
      acquired with UAS imagery. Finally, AY was forecasted using both manual canopy
      volume and individual tree crown area as main factors for olive productivity. AY
      forecast only by using individual crown area made it possible to get a simple and
      cheap forecast tool for a wide range of olive orchards. Finally, the acquired
      information was introduced in a thematic map describing spatial AY variability
      obtained from orthoimage analysis that may be a powerful tool for farmers,
      insurance systems, market forecasts or to detect agronomical problems.

PMID- 28758946
TI  - Hippocampal Proteome of Rats Subjected to the Li-Pilocarpine Epilepsy Model and
      the Effect of Carisbamate Treatment.
AB  - In adult rats, the administration of lithium-pilocarpine (LiPilo) reproduces most
      clinical and neuropathological features of human temporal lobe epilepsy (TLE).
      Carisbamate (CRS) possesses the property of modifying epileptogenesis in this
      model. Indeed, about 50% of rats subjected to LiPilo status epilepticus (SE)
      develop non-convulsive seizures (NCS) instead of motor seizures when treated with
      CRS. However, the mechanisms underlying these effects remain unknown. The aim of
      this study was to perform a proteomic analysis in the hippocampus of rats
      receiving LiPilo and developing motor seizures or NCS following CRS treatment.
      Fifteen adult male Sprague-Dawley rats were used. SE was induced by LiPilo
      injection. CRS treatment was initiated at 1 h and 9 h after SE onset and
      maintained for 7 days, twice daily. Four groups were studied after video-EEG
      control of the occurrence of motor seizures: a control group receiving saline (CT
      n = 3) and three groups that underwent SE: rats treated with diazepam (DZP n =
      4), rats treated with CRS displaying NCS (CRS-NCS n = 4) or motor seizures (CRS
      TLE n = 4). Proteomic analysis was conducted by 2D-SDS-PAGE. Twenty-four proteins
      were found altered. In the CRS-NCS group, proteins related to glycolysis and ATP
      synthesis were down-regulated while proteins associated with pyruvate catabolism
      were up-regulated. Moreover, among the other proteins differentially expressed,
      we found proteins related to inflammatory processes, protein folding, tissue
      regeneration, response to oxidative stress, gene expression, biogenesis of
      synaptic vesicles, signal transduction, axonal transport, microtubule formation,
      cell survival, and neuronal plasticity. Our results suggest a global reduction of
      glycolysis and cellular energy production that might affect brain excitability.
      In addition, CRS seems to modulate proteins related to many other pathways that
      could significantly participate in the epileptogenesis-modifying effect observed.

PMID- 28758944
TI  - Interactions between the Kynurenine and the Endocannabinoid System with Special
      Emphasis on Migraine.
AB  - Both the kynurenine and the endocannabinoid systems are involved in several
      neurological disorders, such as migraine and there are increasing number of
      reports demonstrating that there are interactions of two systems. Although their
      cooperation has not yet been implicated in migraine, there are reports suggesting
      this possibility. Additionally, the individual role of the endocannabinoid and
      kynurenine system in migraine is reviewed here first, focusing on
      endocannabinoids, kynurenine metabolites, in particular kynurenic acid. Finally,
      the function of NMDA and cannabinoid receptors in the trigeminal system-which has
      a crucial role in the pathomechanisms of migraine-will also be discussed. The
      interaction of the endocannabinoid and kynurenine system has been demonstrated to
      be therapeutically relevant in a number of pathological conditions, such as
      cannabis addiction, psychosis, schizophrenia and epilepsy. Accordingly, the cross
      talk of these two systems may imply potential mechanisms related to migraine, and
      may offer new approaches to manage the treatment of this neurological disorder.

PMID- 28758947
TI  - Adiponectin, Leptin, and Leptin Receptor in Obese Patients with Type 2 Diabetes
      Treated with Insulin Detemir.
AB  - The aim of the present study is to quantitatively assess the expression of
      selected regulatory molecules, such as leptin, leptin receptor, and adiponectin
      in the blood of obese patients with type 2 diabetes both before treatment and
      after six months of pharmacological therapy with the long-lasting insulin
      analogue, insulin detemir. A significant decrease in the analysed regulatory
      molecules, i.e., leptin receptor and adiponectin, was found in blood plasma of
      the patients with untreated type 2 diabetes. These changes were accompanied by an
      increase in plasma leptin concentrations. Insulin treatment resulted in the
      normalization of plasma leptin receptor and adiponectin concentrations. The
      circulating leptin level did not change following anti-diabetic therapy with
      insulin detemir. Gender was a significant factor modifying the circulating level
      of all the analysed regulatory active compounds. Bioinformatic analysis was
      performed using Matlab with the Signal Processing Toolbox. The conducted
      discriminant analysis revealed that the leptin receptor, Deltaw(19), and
      adiponectin, Deltaw(21), were the parameters undergoing the most significant
      quantitative changes during the six-month therapy with insulin detemir. The
      conducted examinations indicated the contribution of adipocytokines-the
      biologically-active mediators of systemic metabolism, such as leptin and
      adiponectin in the pathomechanism of disorders being the basis for obesity which
      leads to development of insulin resistance, which, in turn, results in the
      occurrence of type 2 diabetes.

PMID- 28758949
TI  - Potential New Non-Invasive Therapy Using Artificial Oxygen Carriers for Pre
      Eclampsia.
AB  - The molecular mechanisms of pre-eclampsia are being increasingly clarified in
      animals and humans. With the uncovering of these mechanisms, preventive therapy
      strategies using chronic infusion of adrenomedullin, vascular endothelial growth
      factor-121 (VEGF-121), losartan, and sildenafil have been proposed to block
      narrow spiral artery formation in the placenta by suppressing related possible
      factors for pre-eclampsia. However, although such preventive treatments have been
      partly successful, they have failed in ameliorating fetal growth restriction and
      carry the risk of possible side-effects of drugs on pregnant mothers. In this
      study, we attempted to develop a new symptomatic treatment for pre-eclampsia by
      directly rescuing placental ischemia with artificial oxygen carriers (hemoglobin
      vesicles: HbV) since previous data indicate that placental ischemia/hypoxia may
      alone be sufficient to lead to pre-eclampsia through up-regulation of sFlt-1, one
      of the main candidate molecules for the cause of pre-eclampsia. Using a rat
      model, the present study demonstrated that a simple treatment using hemoglobin
      vesicles for placental ischemia rescues placental and fetal hypoxia, leading to
      appropriate fetal growth. The present study is the first to demonstrate
      hemoglobin vesicles successfully decreasing maternal plasma levels of sFlt-1 and
      ameliorating fetal growth restriction in the pre-eclampsia rat model (p < 0.05,
      one-way ANOVA). In future, chronic infusion of hemoglobin vesicles could be a
      potential effective and noninvasive therapy for delaying or even alleviating the
      need for Caesarean sections in pre-eclampsia.

PMID- 28758948
TI  - Polycomb Repressor Complex 2 in Genomic Instability and Cancer.
AB  - Polycomb repressor complexes PRC1 and PRC2 regulate chromatin compaction and gene
      expression, and are widely recognized for their fundamental contributions to
      developmental processes. Herein, we summarize the existing evidence and molecular
      mechanisms linking PRC-mediated epigenetic aberrations to genomic instability and
      malignancy, with a particular focus on the role of deregulated PRC2 in tumor
      suppressor gene expression, the DNA damage response, and the fidelity of DNA
      replication. We also discuss some of the recent advances in the development of
      pharmacological and dietary interventions affecting PRC2, which point to
      promising applications for the prevention and management of human malignancies.

PMID- 28758950
TI  - TGFbeta Controls Ovarian Cancer Cell Proliferation.
AB  - There have been no major improvements in the overall survival of ovarian cancer
      patients in recent decades. Even though more accurate surgery and more effective
      treatments are available, the mortality rate remains high. Given the differences
      in origin and the heterogeneity of these tumors, research to elucidate the
      signaling pathways involved is required. The Transforming Growth Factor (TGFbeta)
      family controls different cellular responses in development and cell homeostasis.
      Disruption of TGFbeta signaling has been implicated in many cancers, including
      ovarian cancer. This article considers the involvement of TGFbeta in ovarian
      cancer progression, and reviews the various mechanisms that enable the TGFbeta
      signaling pathway to control ovarian cancer cell proliferation. These mechanistic
      explanations support the therapeutic use of TGFbeta inhibitors in ovarian cancer,
      which are currently in the early phases of development.

PMID- 28758951
TI  - Iron Supplementation during Three Consecutive Days of Endurance Training
      Augmented Hepcidin Levels.
AB  - Iron supplementation contributes an effort to improving iron status among
      athletes, but it does not always prevent iron deficiency. In the present study,
      we explored the effect of three consecutive days of endurance training (twice
      daily) on the hepcidin-25 (hepcidin) level. The effect of iron supplementation
      during this period was also determined. Fourteen male endurance athletes were
      enrolled and randomly assigned to either an iron-treated condition (Fe condition,
      n = 7) or a placebo condition (Control condition; CON, n = 7). They engaged in
      two 75-min sessions of treadmill running at 75% of maximal oxygen uptake on three
      consecutive days (days 1-3). The Fe condition took 12 mg of iron twice daily (24
      mg/day), and the CON condition did not. On day 1, both conditions exhibited
      significant increases in serum hepcidin and plasma interleukin-6 levels after
      exercise (p < 0.05). In the CON condition, the hepcidin level did not change
      significantly throughout the training period. However, in the Fe condition, the
      serum hepcidin level on day 4 was significantly higher than that of the CON
      condition (p < 0.05). In conclusion, the hepcidin level was significantly
      elevated following three consecutive days of endurance training when moderate
      doses of iron were taken.

PMID- 28758952
TI  - Sparse Representation Based Frequency Detection and Uncertainty Reduction in
      Blade Tip Timing Measurement for Multi-Mode Blade Vibration Monitoring.
AB  - The accurate monitoring of blade vibration under operating conditions is
      essential in turbo-machinery testing. Blade tip timing (BTT) is a promising non
      contact technique for the measurement of blade vibrations. However, the BTT
      sampling data are inherently under-sampled and contaminated with several
      measurement uncertainties. How to recover frequency spectra of blade vibrations
      though processing these under-sampled biased signals is a bottleneck problem. A
      novel method of BTT signal processing for alleviating measurement uncertainties
      in recovery of multi-mode blade vibration frequency spectrum is proposed in this
      paper. The method can be divided into four phases. First, a single measurement
      vector model is built by exploiting that the blade vibration signals are sparse
      in frequency spectra. Secondly, the uniqueness of the nonnegative sparse solution
      is studied to achieve the vibration frequency spectrum. Thirdly, typical sources
      of BTT measurement uncertainties are quantitatively analyzed. Finally, an
      improved vibration frequency spectra recovery method is proposed to get a
      guaranteed level of sparse solution when measurement results are biased.
      Simulations and experiments are performed to prove the feasibility of the
      proposed method. The most outstanding advantage is that this method can prevent
      the recovered multi-mode vibration spectra from being affected by BTT measurement
      uncertainties without increasing the probe number.

PMID- 28758953
TI  - Plant Virus Expression Vectors: A Powerhouse for Global Health.
AB  - Plant-made biopharmaceuticals have long been considered a promising technology
      for providing inexpensive and efficacious medicines for developing countries, as
      well as for combating pandemic infectious diseases and for use in personalized
      medicine. Plant virus expression vectors produce high levels of pharmaceutical
      proteins within a very short time period. Recently, plant viruses have been
      employed as nanoparticles for novel forms of cancer treatment. This review
      provides a glimpse into the development of plant virus expression systems both
      for pharmaceutical production as well as for immunotherapy.

PMID- 28758955
TI  - Nanoporous Structure Formation on the Surface of InSb by Ion Beam Irradiation.
AB  - Nanoporous structures have a great potential for application in electronic and
      photonic materials, including field effect transistors, photonic crystals, and
      quantum dots. The control of size and shape is important for such applications.
      In this study, nanoporous structure formation on the indium antimonide (InSb)
      surface was investigated using controlled focused ion beam irradiation. Upon
      increasing the ion dose, the structures grew larger, and the shapes changed from
      voids to pillars. The structures also became larger when the ion flux (high-dose)
      and accelerating voltage were increased. The structure grew obliquely on the
      substrate by following the ion beam irradiation of 45 degrees . The shapes of the
      structures formed by superimposed ion beam irradiation were affected by primary
      irradiation conditions. The nanostructural features on the InSb surface were easy
      to control by changing the ion beam conditions.

PMID- 28758954
TI  - Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and
      Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway.
AB  - Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern
      Asia to improve memory. In this work, we investigated the neuroprotective and
      neuritogenic effects of the secondary metabolites isolated from the MeOH extract
      of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new
      dihydropyridine compound (6) and one new natural product (2) together with five
      known compounds (1,3-5,7) were obtained and their structures were elucidated by
      spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for
      bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester (1) and a
      cyathane diterpenoid, erincine A (3), not only potentiated NGF-induced neurite
      outgrowth but also protected neuronally-differentiated cells against deprivation
      of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced
      neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed
      that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3
      promoted NGF-induced neurite outgrowth in PC12 cells.

PMID- 28758956
TI  - Fruit and Vegetable Intake Patterns and Their Associations with Sociodemographic
      Characteristics, Anthropometric Status and Nutrient Intake Profiles among
      Malaysian Children Aged 1-6 Years.
AB  - This study aimed to assess fruit and vegetable intake patterns and their
      associations with sociodemographic characteristics, anthropometric status and
      nutrient intake profiles among Malaysian children aged 1-6 years. Using the
      Malaysian dataset of South East Asian Nutrition Surveys (SEANUTS Malaysia), a
      total of 1307 children aged 1-6 years with complete datasets were included in
      this analysis. Dietary intake was assessed using age-specific, validated food
      frequency questionnaires. On average, Malaysian children consumed 0.91 and 1.07
      servings of fruits and vegetables per day, respectively. Less than one-fifth of
      the children achieved the daily recommended servings of fruits (11.7%) and
      vegetables (15.8%). Fruit intake was associated with age, parental educational
      level and geographical region, and vegetable intake was associated with ethnicity
      and geographical region. There was little evidence of an association between
      fruit and vegetable intake and children's anthropometric status, but an adequate
      intake of fruits and vegetables contributed significantly and differently to
      children's micronutrient intake. Future nutrition interventions should focus on
      addressing the sociodemographic determinants and be tailored to the needs of the
      low consumers to more effectively promote and encourage the adequate intake of
      fruit and vegetables among young children.

PMID- 28758958
TI  - Evaluation of Antioxidant Activity and Growth Control Properties of Nonoscale
      Structure Produced from Aloe vera var. littoralis Extract on Clinical Isolates of
      Salmonella.
AB  - The aim of the study was to examine antibacterial properties of microemulsion
      structure produced from Aloe vera var. littoralis extract as a new tool of
      nanoscale drug-like materials. Aloe vera var. littoralis (A. littoralis) extract
      was prepared by distillation method. A nonocarrier structure in the microemulsion
      system was prepared from the extract. Serial concentrations were prepared from 8
      mg/mL extract and the nonocarrier containing 0.1 mg/mL pure extract and were
      evaluated by a disk diffusion method for 35 Salmonella clinical isolates. Minimum
      inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were
      determined by microbroth dilution assay using MTT (3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide) method by an enzyme-linked immunosorbent
      assay(ELISA) Microplate Reader apparatus. Antioxidant activity of the extract was
      determined by measuring the ferric reducing ability of plasma (FRAP) assay. From
      35 clinical isolates of Salmonella, 17 isolates-including resistant isolates of
      S.E.1103 and S.E.49-had a zone of inhibition (ZI) of 7 to 32 mm in 0.007 mg/mL of
      the extract. S.E.76 isolate exposed to 30 ug/mL ceftazidime disk had a ZI of 12
      mm but had 10 mm in 7ug/mL of A. littoralis extract. The inhibitory effect of a
      nanocarrier at a concentration of 25 ug/mL by 20 mm ZI was comparable by the
      ceftazidime (30 ug/mL) effect. MIC50 was 0.25 mg/mL and MBC50 was 0.5 mg/mL by
      MTT method for the extract. It was shown that A.littoralis extract had
      antioxidant activity of 31.67 uM/mg that could be increased based on
      concentration. It was concluded that the nanocarrier had a significant effect on
      the studied isolates in comparison with ordinary antibiotics and had potential
      for use as a natural antioxidant and antimicrobial material in complementary
      medicine.

PMID- 28758957
TI  - Transcriptome Analysis Reveals Increases in Visceral Lipogenesis and Storage and
      Activation of the Antigen Processing and Presentation Pathway during the Mouth
      Opening Stage in Zebrafish Larvae.
AB  - The larval phase of the fish life cycle has the highest mortality, particularly
      during the transition from endogenous to exogenous feeding. However, the
      transcriptional events underlying these processes have not been fully
      characterized. To understand the molecular mechanisms underlying mouth-opening
      acclimation, RNA-seq was used to investigate the transcriptional profiles of the
      endogenous feeding, mixed feeding and exogenous feeding stages of zebrafish
      larvae. Differential expression analysis showed 2172 up-regulated and 2313 down
      regulated genes during this stage. Genes associated with the assimilation of
      exogenous nutrients such as the arachidonic acid metabolism, linoleic acid
      metabolism, fat digestion and absorption, and lipogenesis were activated
      significantly, whereas dissimilation including the cell cycle, homologous
      recombination, and fatty acid metabolism were inhibited, indicating a
      physiological switch for energy storage occurred during the mouth-opening stage.
      Moreover, the immune recognition involved in the antigen processing and
      presentation pathway was activated and nutritional supply seemed to be required
      in this event confirmed by qPCR. These results suggested the energy utilization
      during the mouth-opening stage is more tended to be reserved or used for some
      important demands, such as activity regulation, immune defense, and lipid
      deposition, instead of rapid growth. The findings of this study are important for
      understanding the physiological switches during the mouth-opening stage.

PMID- 28758959
TI  - Challenges in Expanding Access to Dialysis in South Africa-Expensive Modalities,
      Cost Constraints and Human Rights.
AB  - South Africa is a country with two distinct health sectors, which are both
      characterised by inequalities. Within this context, patients with end stage renal
      disease face unique and sometimes impenetrable barriers to accessing dialysis.
      There are a number of reasons for this situation. These include: the South
      African government's endorsement of discordant, unequal policies, which
      disadvantage the most vulnerable; a lack of robust national guidelines; and
      divisive rationing practices, which are ad hoc and place the burden of
      responsibility for rationing dialysis on the clinician. In this paper, we trace
      the socio-economic mechanisms of how we have come to be in this situation, and
      overlay this with a detailed examination of South African legislation. Finally,
      we make comprehensive practical recommendations for rectifying the situation,
      which include engagement with key stakeholders, public-private partnerships, and
      more equitable funding mechanisms.

PMID- 28758960
TI  - Ultrasound for Early Detection of Joint Disease in Patients with Hemophilic
      Arthropathy.
AB  - Joint bleeding represents the most commonly reported type of hemorrhage in
      patients affected by hemophilia. Although the widespread use of prophylaxis has
      been able to significantly reduce the onset of arthropathy, it has been shown
      that a non-negligible percentage of patients develop degenerative changes in
      their joints despite this type of treatment. Thus, periodic monitoring of the
      joint status in hemophilia patients has been recommended to identify early
      arthropathic changes and prevent the development or progression of hemophilic
      arthropathy. Ultrasound (US) has proven able to detect and quantify the most
      relevant biomarkers of disease activity (i.e., joint effusion and synovial
      hypertrophy) and degenerative damages (i.e., osteo-chondral changes) by means of
      scoring scales of increasing disease severity. In the present review, we have
      detailed major literature evidence about the use of US to assess joint status in
      hemophilia patients, focusing on signs of disease activity and degenerative
      damages. In particular, we have discussed recent evidence about "point-of-care"
      use patients with hemophilia.

PMID- 28758961
TI  - Nrf2-Knockout Protects from Intestinal Injuries in C57BL/6J Mice Following
      Abdominal Irradiation with gamma Rays.
AB  - Radiation-induced intestinal injuries (RIII) commonly occur in patients who
      suffer from pelvic or abdominal cancer. Nuclear factor-erythroid 2-related factor
      2 (Nrf2) is a key transcriptional regulator of antioxidant, and the
      radioprotective role of Nrf2 is found in bone marrow, lung, and intestine, etc.
      Here, we investigated the effect of Nrf2 knockout on radiation-induced intestinal
      injuries using Nrf2 knockout (Nrf2-/-) mice and wild-type (Nrf2+/+) C57BL/6J mice
      following 13 Gy abdominal irradiation (ABI). It was found that Nrf2 knockout
      promoted the survival of irradiated mice, protected the crypt-villus structure of
      the small intestine, and elevated peripheral blood lymphocyte count and thymus
      coefficients. The DNA damage of peripheral blood lymphocytes and the apoptosis of
      intestinal epithelial cells (IECs) of irradiated Nrf2-/- mice were decreased.
      Furthermore, compared with that of Nrf2+/+ mice, Nrf2 knockout increased the
      number of Lgr5+ intestinal stem cells (ISCs) and their daughter cells including
      Ki67+ transient amplifying cells, Villin+ enterocytes, and lysozyme+ Paneth
      cells. Nuclear factor-kappaB (NF-kappaB) was accumulated in the crypt base nuclei
      of the small intestine, and the mRNA expression of NF-kappaB target genes Bcl-2,
      uPA, and Xiap of the small intestine from irradiated Nrf2-/- mice were increased.
      Collectively, Nrf2 knockout has the protective effect on small intestine damage
      following abdominal irradiation by prompting the proliferation and
      differentiation of Lgr5+ intestinal stem cells and activation of NF-kappaB.

PMID- 28758962
TI  - A Population-Based, Cross-Sectional Study Examining Health Services Deficits of
      US Veterans Using 2014 Behavioral Risk Factor Surveillance System Data: Is Rural
      Residency an Independent Risk Factor after Controlling for Multiple Covariates?
AB  - Introduction: In 2014, it was reported that there was a backlog of an estimated
      1.2 million claims nationwide at the United States Veterans Administration (VA).
      This ecological occurrence opened up a space for asking and answering some
      important questions about health service deficits (HSD) of US veterans, which is
      the focus of the research reported on in this paper. The purpose of this study
      was to ascertain if rural veterans were more likely to experience HSDs than urban
      military veterans after controlling for a number of covariates. Methods:
      Bivariate and multivariate data analysis strategies were used to examine 2014
      Behavioral Risk Factor Surveillance System (BRFSS) survey data. HSD was the
      dependent variable. Results: Two multivariate models were tested. The first
      logistic regression analysis yielded that rural veterans had higher odds of
      having at least one HSD. The second yielded that rural US veterans in 2014 who
      had higher odds of having at least one HSD were: 18-64 years of age, unemployed
      seeking employment, living in households with annual incomes lower than $75,000,
      without a university degree, not part of a married or unmarried couple, a current
      smoker, and/or a binge drinker within the last 30 days. Conclusions: The study
      described here fills identified epidemiological gaps in our knowledge regarding
      rural US military veterans and HSDs. The findings are not only interesting but
      important, and should be used to inform interventions to reduce HSDs for rural
      veterans.

PMID- 28758963
TI  - A Miniaturized QEPAS Trace Gas Sensor with a 3D-Printed Acoustic Detection
      Module.
AB  - A 3D printing technique was introduced to a quartz-enhanced photoacoustic
      spectroscopy (QEPAS) sensor and is reported for the first time. The acoustic
      detection module (ADM) was designed and fabricated using the 3D printing
      technique and the ADM volume was compressed significantly. Furthermore, a small
      grin lens was used for laser focusing and facilitated the beam adjustment in the
      3D-printed ADM. A quartz tuning fork (QTF) with a low resonance frequency of
      30.72 kHz was used as the acoustic wave transducer and acetylene (C2H2) was
      chosen as the analyte. The reported miniaturized QEPAS trace gas sensor is useful
      in actual sensor applications.

PMID- 28758964
TI  - Effects of Popular Diets without Specific Calorie Targets on Weight Loss
      Outcomes: Systematic Review of Findings from Clinical Trials.
AB  - The present review examined the evidence base for current popular diets, as
      listed in the 2016 U.S. News & World Report, on short-term (<=six months) and
      long-term (>=one year) weight loss outcomes in overweight and obese adults. For
      the present review, all diets in the 2016 U.S. News & World Report Rankings for
      "Best Weight-Loss Diets", which did not involve specific calorie targets, meal
      replacements, supplementation with commercial products, and/or were not
      categorized as "low-calorie" diets were examined. Of the 38 popular diets listed
      in the U.S. News & World Report, 20 met our pre-defined criteria. Literature
      searches were conducted through PubMed, Cochrane Library, and Web of Science
      using preset key terms to identify all relevant clinical trials for these 20
      diets. A total of 16 articles were identified which reported findings of clinical
      trials for seven of these 20 diets: (1) Atkins; (2) Dietary Approaches to Stop
      Hypertension (DASH); (3) Glycemic-Index; (4) Mediterranean; (5) Ornish; (6)
      Paleolithic; and (7) Zone. Of the diets evaluated, the Atkins Diet showed the
      most evidence in producing clinically meaningful short-term (<=six months) and
      long-term (>=one-year) weight loss. Other popular diets may be equally or even
      more effective at producing weight loss, but this is unknown at the present time
      since there is a paucity of studies on these diets.

PMID- 28758965
TI  - Identification and Quantification of Celery Allergens Using Fiber Optic Surface
      Plasmon Resonance PCR.
AB  - Abstract: Accurate identification and quantification of allergens is key in
      healthcare, biotechnology and food quality and safety. Celery (Apium graveolens)
      is one of the most important elicitors of food allergic reactions in Europe.
      Currently, the golden standards to identify, quantify and discriminate celery in
      a biological sample are immunoassays and two-step molecular detection assays in
      which quantitative PCR (qPCR) is followed by a high-resolution melting analysis
      (HRM). In order to provide a DNA-based, rapid and simple detection method
      suitable for one-step quantification, a fiber optic PCR melting assay (FO-PCR-MA)
      was developed to determine different concentrations of celery DNA (1 pM-0.1 fM).
      The presented method is based on the hybridization and melting of DNA-coated gold
      nanoparticles to the FO sensor surface in the presence of the target gene
      (mannitol dehydrogenase, Mtd). The concept was not only able to reveal the
      presence of celery DNA, but also allowed for the cycle-to-cycle quantification of
      the target sequence through melting analysis. Furthermore, the developed bioassay
      was benchmarked against qPCR followed by HRM, showing excellent agreement (R2 =
      0.96). In conclusion, this innovative and sensitive diagnostic test could further
      improve food quality control and thus have a large impact on allergen induced
      healthcare problems.

PMID- 28758966
TI  - Variability of Creatine Metabolism Genes in Children with Autism Spectrum
      Disorder.
AB  - Creatine deficiency syndrome (CDS) comprises three separate enzyme deficiencies
      with overlapping clinical presentations: arginine:glycine amidinotransferase
      (GATM gene, glycine amidinotransferase), guanidinoacetate methyltransferase (GAMT
      gene), and creatine transporter deficiency (SLC6A8 gene, solute carrier family 6
      member 8). CDS presents with developmental delays/regression, intellectual
      disability, speech and language impairment, autistic behaviour, epileptic
      seizures, treatment-refractory epilepsy, and extrapyramidal movement disorders;
      symptoms that are also evident in children with autism. The objective of the
      study was to test the hypothesis that genetic variability in creatine metabolism
      genes is associated with autism. We sequenced GATM, GAMT and SLC6A8 genes in 166
      patients with autism (coding sequence, introns and adjacent untranslated
      regions). A total of 29, 16 and 25 variants were identified in each gene,
      respectively. Four variants were novel in GATM, and 5 in SLC6A8 (not present in
      the 1000 Genomes, Exome Sequencing Project (ESP) or Exome Aggregation Consortium
      (ExAC) databases). A single variant in each gene was identified as non
      synonymous, and computationally predicted to be potentially damaging. Nine
      variants in GATM were shown to have a lower minor allele frequency (MAF) in the
      autism population than in the 1000 Genomes database, specifically in the East
      Asian population (Fisher's exact test). Two variants also had lower MAFs in the
      European population. In summary, there were no apparent associations of variants
      in GAMT and SLC6A8 genes with autism. The data implying there could be a lower
      association of some specific GATM gene variants with autism is an observation
      that would need to be corroborated in a larger group of autism patients, and with
      sub-populations of Asian ethnicities. Overall, our findings suggest that the
      genetic variability of creatine synthesis/transport is unlikely to play a part in
      the pathogenesis of autism spectrum disorder (ASD) in children.

PMID- 28758967
TI  - On-Chip High-Finesse Fabry-Perot Microcavities for Optical Sensing and Quantum
      Information.
AB  - For applications in sensing and cavity-based quantum computing and metrology,
      open-access Fabry-Perot cavities-with an air or vacuum gap between a pair of high
      reflectance mirrors-offer important advantages compared to other types of
      microcavities. For example, they are inherently tunable using MEMS-based
      actuation strategies, and they enable atomic emitters or target analytes to be
      located at high field regions of the optical mode. Integration of curved-mirror
      Fabry-Perot cavities on chips containing electronic, optoelectronic, and
      optomechanical elements is a topic of emerging importance. Micro-fabrication
      techniques can be used to create mirrors with small radius-of-curvature, which is
      a prerequisite for cavities to support stable, small-volume modes. We review
      recent progress towards chip-based implementation of such cavities, and highlight
      their potential to address applications in sensing and cavity quantum
      electrodynamics.

PMID- 28758968
TI  - Middle Cerebral Artery Stroke as Amusement Park Injury: Case Report and Review of
      the Literature.
AB  - Strokes as amusement park injuries are rare, but have been reported in the
      literature. Only about 20 cases of cerebrovascular accidents after amusement park
      visits have been described. We report a healthy 12-year-old boy who presented
      with facial droop, slurred speech, and inability to use his right arm after
      riding roller coasters at a local amusement park. He was evaluated and found to
      have a left middle cerebral artery (MCA) infarction. The patient was treated with
      anticoagulants and has recovered with no major residual symptoms. It is likely
      that his neurological symptoms occurred due to the high head accelerations
      experienced on the roller coasters, which are more detrimental to children due to
      immature cervical spine development and muscle strength. Early diagnosis of
      dissection and stroke results in a favorable prognosis. Providers and parents
      should be aware of the potential risk of roller coasters and act quickly on
      neurologic changes in children that have recently been to an amusement park.

PMID- 28758969
TI  - Assessment of Bone Metastases in Patients with Prostate Cancer-A Comparison
      between 99mTc-Bone-Scintigraphy and [68Ga]Ga-PSMA PET/CT.
AB  - PURPOSE: Bone scintigraphy is the standard of reference in bone metastases in
      prostate cancer patients. However, new radiotracers employed in prostate-specific
      membrane antigen (PSMA)-ligands has led to the growing importance of PET/CT as
      diagnostic tool. The aim of our study was to investigate the difference between
      bone scan and PSMA-PET/CT for the detection of bone metastases in prostate
      cancer. METHODS: Thirty patients with bone metastases originating from prostate
      cancer were examined by 99mTc-MDP bone scan and 68Ga-PSMA-PET/CT within an
      average of 21 days. Bone scans were analyzed visually according to the number of
      lesions and using the software package ExiniBONE by Exini Diagnostics. PET/CT
      data was analyzed visually. Numbers of detected lesions were compared for the
      different methods for the whole patient and for different regions. In addition,
      results were compared to serum prostate-specific antigen (PSA), alkaline
      phosphatase (ALP), bone alkaline phosphatase (bALP), pro gastrin releasing
      peptide (pGRP) and eastern cooperative oncology group (ECOG) performance status.
      RESULTS: In the bone scans, visual and semiautomatic lesion detection showed
      similar results with an average of 19.4 and 17.8 detected bone lesion per
      patient. However, in PSMA-PET/CT, on average double the numbers of lesions (40.0)
      were detected. The largest differences were found in the thorax and pelvis, which
      can be explained by the advantages of tomographic imaging. Bland-Altman analysis
      showed greater differences in patients with large numbers of bone metastases.
      CONCLUSION: No significant difference was found when using semiautomatic analysis
      compared to visual reading for bone scans. Fewer bone metastases were detected in
      bone scans than in PSMA-PET/CT. However, in none of our patients would the
      difference have led to clinical consequences. Therefore, it seems that for
      patients undergoing PSMA-PET/CT, there is no need to perform additional bone
      scans if the appropriate PET/CT protocols are applied.

PMID- 28758970
TI  - Practical Considerations before Installing Ground-Based Geodetic Infrastructure
      for Integrated InSAR and cGNSS Monitoring of Vertical Land Motion.
AB  - Continuously operating Global Navigation Satellite Systems (cGNSS) can be used to
      convert relative values of vertical land motion (VLM) derived from
      Interferometric Synthetic Aperture Radar (InSAR) to absolute values in a global
      or regional reference frame. Artificial trihedral corner reflectors (CRs) provide
      high-intensity and temporally stable reflections in SAR time series imagery, more
      so than naturally occurring permanent scatterers. Therefore, it is logical to co
      locate CRs with cGNSS as ground-based geodetic infrastructure for the integrated
      monitoring of VLM. We describe the practical considerations for such co-locations
      using four case-study examples from Perth, Australia. After basic initial
      considerations such as land access, sky visibility and security, temporary test
      deployments of co-located CRs with cGNSS should be analysed together to determine
      site suitability. Signal to clutter ratios from SAR imagery are used to determine
      potential sites for placement of the CR. A significant concern is whether the co
      location of a deliberately designed reflecting object generates unwanted
      multipath (reflected signals) in the cGNSS data. To mitigate against this, we
      located CRs >30 m from the cGNSS with no inter-visibility. Daily RMS values of
      the zero-difference ionosphere-free carrier-phase residuals, and ellipsoidal
      heights from static precise point positioning GNSS processing at each co-located
      site were then used to ascertain that the CR did not generate unwanted cGNSS
      multipath. These steps form a set of recommendations for the installation of such
      geodetic ground-infrastructure, which may be of use to others wishing to
      establish integrated InSAR-cGNSS monitoring of VLM elsewhere.

PMID- 28758971
TI  - Tricetin Induces Apoptosis of Human Leukemic HL-60 Cells through a Reactive
      Oxygen Species-Mediated c-Jun N-Terminal Kinase Activation Pathway.
AB  - Tricetin is a dietary flavonoid with cytostatic properties and antimetastatic
      activities in various solid tumors. The anticancer effect of tricetin in nonsolid
      tumors remains unclear. Herein, the molecular mechanisms by which tricetin exerts
      its anticancer effects on acute myeloid leukemia (AML) cells were investigated.
      Results showed that tricetin inhibited cell viability in various types of AML
      cell lines. Tricetin induced morphological features of apoptosis such as
      chromatin condensation and phosphatidylserine (PS) externalization, and
      significantly activated proapoptotic signaling including caspase-8, -9, and -3
      activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells. Of
      note, tricetin-induced cell growth inhibition was dramatically reversed by a pan
      caspase and caspase-8- and -9-specific inhibitors, suggesting that this compound
      mainly acts through a caspase-dependent pathway. Moreover, treatment of HL-60
      cells with tricetin induced sustained activation of extracellular signal
      regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), and inhibition of ERK
      and JNK by their specific inhibitors respectively promoted and abolished tricetin
      induced cell apoptosis. Dichlorofluorescein (DCF) staining showed that
      intracellular reactive oxygen species (ROS) levels were higher in tricetin
      treated HL-60 cells compared to the control group. Moreover, an ROS scavenger, N
      acetylcysteine (NAC), reversed tricetin-induced JNK activation and subsequent
      cell apoptosis. In conclusion, our results indicated that tricetin induced cell
      death of leukemic HL-60 cells through induction of intracellular oxidative stress
      following activation of a JNK-mediated apoptosis pathway. A combination of
      tricetin and an ERK inhibitor may be a better strategy to enhance the anticancer
      activities of tricetin in AML.

PMID- 28758972
TI  - Mutations of Pre-mRNA Splicing Regulatory Elements: Are Predictions Moving
      Forward to Clinical Diagnostics?
AB  - For more than three decades, researchers have known that consensus splice sites
      alone are not sufficient regulatory elements to provide complex splicing
      regulation. Other regulators, so-called splicing regulatory elements (SREs) are
      needed. Most importantly, their sequence variants often underlie the development
      of various human disorders. However, due to their variable location and high
      degeneracy, these regulatory sequences are also very difficult to recognize and
      predict. Many different approaches aiming to identify SREs have been tried, often
      leading to the development of in silico prediction tools. While these tools were
      initially expected to be helpful to identify splicing-affecting mutations in
      genetic diagnostics, we are still quite far from meeting this goal. In fact, most
      of these tools are not able to accurately discern the SRE-affecting pathological
      variants from those not affecting splicing. Nonetheless, several recent
      evaluations have given appealing results (namely for EX-SKIP, ESRseq and
      Hexplorer predictors). In this review, we aim to summarize the history of the
      different approaches to SRE prediction, and provide additional validation of
      these tools based on patients' clinical data. Finally, we evaluate their
      usefulness for diagnostic settings and discuss the challenges that have yet to be
      met.

PMID- 28758973
TI  - CeO2 Nanorods Embedded in Ni(OH)2 Matrix for the Non-Enzymatic Detection of
      Glucose.
AB  - The electrode based on cerium oxide (CeO2) nanorods embedded in nickel hydroxide
      (Ni(OH)2) matrix were prepared and used for detecting glucose non-enzymatically.
      The materials were characterized by X-ray diffraction, transmission electron
      microscopy (TEM), and so on. The results indicate that the response of
      CeO2/Ni(OH)2 nanocomposite are significantly improved due to the synergetic
      effect between CeO2 and Ni(OH)2. The optimum CeO2/Ni(OH)2 nanocomposite electrode
      exhibits a detection range from 2 MUM to 6.62 mM, a sensitivity of 594 MUA mM-1
      cm-2, an estimated detection limit of 1.13 MUM, and a response time less than 5
      s. In addition, this biosensor also shows good selectivity, long term stability,
      and accurate measurement in juice on sale.

PMID- 28758976
TI  - Astragalosidic Acid: A New Water-Soluble Derivative of Astragaloside IV Prepared
      Using Remarkably Simple TEMPO-Mediated Oxidation.
AB  - There is an urgent need for a water-soluble derivative of astragaloside IV for
      drug R&D. In the present study, a remarkably simple method for the preparation of
      such a water-soluble derivative of astragaloside IV has been developed. This
      protocol involves oxidative 2,2,6,6-tetramethylpiperidine-1-oxyl free radical
      (TEMPO)-mediated transformation of astragaloside IV to its carboxylic acid
      derivative, which is a new compound named astragalosidic acid. The structure of
      astragalosidic acid was elucidated by means of spectroscopic analysis. Its
      cardioprotective activity was investigated using an in vitro model of
      cardiomyocyte damage induced by hypoxia/reoxygenation in H9c2 cells. The
      oxidative TEMPO-mediated transformation proposed in the present study could be
      applied to other natural saponins, offering an effective and convenient way to
      develop a new compound with greatly improved structure-based druggability.

PMID- 28758974
TI  - Immunotherapeutic Concepts to Target Acute Myeloid Leukemia: Focusing on the Role
      of Monoclonal Antibodies, Hypomethylating Agents and the Leukemic
      Microenvironment.
AB  - Intensive chemotherapeutic protocols and allogeneic stem cell transplantation
      continue to represent the mainstay of acute myeloid leukemia (AML) treatment.
      Although this approach leads to remissions in the majority of patients, long-term
      disease control remains unsatisfactory as mirrored by overall survival rates of
      approximately 30%. The reason for this poor outcome is, in part, due to various
      toxicities associated with traditional AML therapy and the limited ability of
      most patients to tolerate such treatment. More effective and less toxic therapies
      therefore represent an unmet need in the management of AML, a disease for which
      therapeutic progress has been traditionally slow when compared to other cancers.
      Several studies have shown that leukemic blasts elicit immune responses that
      could be exploited for the development of novel treatment concepts. To this end,
      early phase studies of immune-based therapies in AML have delivered encouraging
      results and demonstrated safety and feasibility. In this review, we discuss
      opportunities for immunotherapeutic interventions to enhance the potential to
      achieve a cure in AML, thereby focusing on the role of monoclonal antibodies,
      hypomethylating agents and the leukemic microenvironment.

PMID- 28758977
TI  - Seed Coating with Hydro-Absorbers as Potential Mitigation of Early Season Drought
      in Sorghum (Sorghum bicolor L. Moench).
AB  - Climate change poses a threat to sorghum production systems by shifting the onset
      of the rainy season to a later date, increasing the risk of crop failure during
      crop establishment. The effects of drought on sorghum during seedling
      establishment have not been determined. Coating seeds with a water absorbing
      substance offers a way to buffer the seed against insufficient moisture in the
      surrounding soil. Seeds of two different sorghum varieties were coated with one
      of two commercially available hydro-absorbers: Stokosorb(r) and Geohumus(r).
      These hydro-absorbers have the capacity to store water several times their own
      weight. The aim of this study was to compare the effects of the cited hydro
      absorbers on early seedling growth of two sorghum landraces under different
      levels of soil water deficit. Seedlings were grown for 12 days under three water
      availability levels (Field capacity (FC), 50% of FC, and 25% of FC). The
      seedlings under water limited treatments were subsequently re-watered. Biomass,
      root length, plant height, leaf area, and leaf extension rate were monitored in
      two-day intervals for 24 days. Coating strongly affected seedling growth both
      under fully watered and water deficit conditions. Sorghum varieties differed in
      their responses to both soil water deficit and coating materials. In general,
      Stockosorb improved seedling performance under water limited conditions
      particularly by promoting root growth, whereas Geohumus did not.

PMID- 28758975
TI  - Elevated Soluble Urokinase Plasminogen Activator Receptor and Proenkephalin Serum
      Levels Predict the Development of Acute Kidney Injury after Cardiac Surgery.
AB  - Acute kidney injury (AKI) develops in up to 40% of patients after cardiac
      surgery. The soluble urokinase plasminogen activator receptor (suPAR) has been
      identified as a biomarker for incident chronic kidney disease (CKD).
      Proenkephalin (proENK) also has been shown to be a biomarker for renal
      dysfunction. We hypothesized that pre-surgery suPAR and proENK levels might
      predict AKI in patients undergoing cardiac surgery. Consecutive patients (n =
      107) undergoing elective cardiac surgery were studied prospectively. Clinical
      data, laboratory parameters, suPAR and proENK serum levels were assessed before
      operation, after operation and days one and four post-operatively. A total of 21
      (19.6%) patients developed AKI within the first four days after elective surgery.
      Serum levels of suPAR and proENK, but not of creatinine, were significantly
      higher before surgery in these patients compared to those patients without AKI.
      This difference remained significant for suPAR, if patients with or without AKI
      were matched for risk factors (hypertension, diabetes, CKD). If cardiac surgery
      patients with pre-existing CKD (n = 10) were excluded, only pre-operative suPAR
      but not proENK serum levels remained significantly elevated in patients with
      subsequent AKI. Thus, our findings indicate that suPAR may be a predictive
      biomarker for AKI in the context of cardiac surgery, even in patients without
      underlying CKD.

PMID- 28758978
TI  - Dietary Approaches in the Management of Diabetic Patients with Kidney Disease.
AB  - Chronic kidney disease (CKD) is one of the most prevalent complications of
      diabetes, and patients with diabetic kidney disease (DKD) have a substantially
      higher risk of cardiovascular disease and death compared to their non-diabetic
      CKD counterparts. In addition to pharmacologic management strategies, nutritional
      and dietary interventions in DKD are an essential aspect of management with the
      potential for ameliorating kidney function decline and preventing the development
      of other end-organ complications. Among DKD patients with non-dialysis dependent
      CKD, expert panels recommend lower dietary protein intake of 0.8 g/kg of body
      weight/day, while higher dietary protein intake (>1.2 g/kg of body weight/day) is
      advised among diabetic end-stage renal disease patients receiving maintenance
      dialysis to counteract protein catabolism, dialysate amino acid and protein
      losses, and protein-energy wasting. Carbohydrates from sugars should be limited
      to less than 10% of energy intake, and it is also suggested that higher
      polyunsaturated and monounsaturated fat consumption in lieu of saturated fatty
      acids, trans-fat, and cholesterol are associated with more favorable outcomes.
      While guidelines recommend dietary sodium restriction to less than 1.5-2.3 g/day,
      excessively low sodium intake may be associated with hyponatremia as well as
      impaired glucose metabolism and insulin sensitivity. As patients with advanced
      DKD progressing to end-stage renal disease may be prone to the "burnt-out
      diabetes" phenomenon (i.e., spontaneous resolution of hypoglycemia and frequent
      hypoglycemic episodes), further studies in this population are particularly
      needed to determine the safety and efficacy of dietary restrictions in this
      population.

PMID- 28758979
TI  - Suppression of mRNA Nanoparticle Transfection in Human Fibroblasts by Selected
      Interferon Inhibiting Small Molecule Compounds.
AB  - In vitro transcribed (IVT) mRNA is increasingly applied in lieu of DNA to deliver
      reprogramming genes to fibroblasts for stem cell derivation. However, IVT mRNA
      induces interferon (IFN) responses from mammalian cells that reduces transfection
      efficiency. It has been previously suggested that small molecule inhibitors of
      IFN are a viable strategy to enhance mRNA transfection efficiency. Herein, we
      screen a list of commercially available small molecules, including published IFN
      inhibitors, for their potential to enhance mRNA transfection in BJ fibroblasts.
      Transfection enhancement is quantified by relative mean fluorescence intensity of
      translated green fluorescent protein (GFP) in treated cells compared to dimethyl
      sulfoxide treated controls. Within toxicological constrains, all tested small
      molecules did not enhance mRNA transfection in BJ fibroblasts while a third of
      the tested compounds unexpectedly inhibited GFP expression even though IFN-beta
      production is inhibited. Based on the results of our study, we conclude that
      small molecule inhibitors, including IFN inhibitors, tested in this study do not
      enhance in vitro mRNA transfection efficiency in human fibroblasts.

PMID- 28758980
TI  - Effects of PLA Film Incorporated with ZnO Nanoparticle on the Quality Attributes
      of Fresh-Cut Apple.
AB  - A novel nanopackaging film was synthesized by incorporating ZnO nanoparticles
      into a poly-lactic acid (PLA) matrix, and its effect on the quality of fresh-cut
      apple during the period of preservation was investigated at 4 +/- 1  degrees C
      for 14 days. Six wt % cinnamaldehyde was added into the nano-blend film. Scanning
      electron microscope (SEM) analysis showed a rougher cross-section of the nano
      blend films and an X-ray diffraction (XRD) was carried out to determine the
      structure of the ZnO nanoparticles. Compared to the pure PLA film, the nano-blend
      film had a higher water vapor permeability (WVP) and lower oxygen permeability.
      With the increase of the nanoparticles (NPs) in the PLA, the elongation at break
      (epsilon) and elastic modulus (EM) increased, while tensile strength (TS)
      decreased. Thermogravimetric analysis (TGA) presented a relatively good
      thermostability. Most importantly, the physical and biochemical properties of the
      fresh-cut apple were also measured, such as weight loss, firmness, polyphenol
      oxidase (PPO), total phenolic content, browning index (BI), sensory quality, and
      microbiological level. The results indicated that nano-blend packaging films had
      the highest weight loss at the end of storage compared to the pure PLA film;
      however, nanopackaging provided a better retention of firmness, total phenolic
      countent, color, and sensory quality. It also had a remarkable inhibition on the
      growth of microorganisms. Therefore, Nano-ZnO active packaging could be used to
      improve the shelf-life of fresh-cut produce.

PMID- 28758981
TI  - An Efficient Synthesis of Arylated Pyridines from Conjugated Acetylenes and
      Substituted Benzylamines Catalyzed by Base.
AB  - An efficient base-catalyzed synthesis of arylated pyridines has been disclosed.
      This reaction involving conjugated acetylenes and substituted benzylamines
      proceeded smoothly, giving rise to tri-aryl substituted pyridines which are
      biologically relevant compounds in good to excellent yields in N,N
      dimethylformamide (DMF) under air at 140  degrees C with K2CO3 as catalyst.

PMID- 28758983
TI  - A Method to Reduce Non-Nominal Troposphere Error.
AB  - Under abnormal troposphere, Ground-Based Augmentation System (GBAS) is unable to
      eliminate troposphere delay, resulting in non-nominal troposphere error. This
      paper analyzes the troposphere meteorological data of eight International GNSS
      Monitoring Assessment System (iGMAS) stations and 10 International GNSS Service
      (IGS) stations in China and records the most serious conditions during 2015 and
      2016. Simulations show that the average increase in Vertical Protection Level
      (VPL) of all visible satellites under non-nominal troposphere is 2.32 m and that
      more satellites increase the VPL. To improve GBAS integrity, this paper proposes
      a satellite selection method to reduce the non-nominal troposphere error. First,
      the number of satellites in the optimal subset is determined to be 16 based on
      the relationship among VPL, non-nominal troposphere error and satellite geometry.
      Second, the distributions of the optimal satellites are determined. Finally,
      optimal satellites are selected in different elevation ranges. Results show that
      the average VPL increase caused by non-nominal troposphere error is 1.15 m using
      the proposed method. Compared with the brute method and greedy method, the
      running rate of the proposed method is improved by 390.91% and 111.65%,
      respectively. In summary, the proposed method balances the satellite geometry and
      non-nominal troposphere error while minimizing the VPL and improving the running
      rate.

PMID- 28758982
TI  - N-Doped TiO2-Coated Ceramic Membrane for Carbamazepine Degradation in Different
      Water Qualities.
AB  - The photocatalytic degradation of the model pollutant carbamazepine (CBZ) was
      investigated under simulated solar irradiation with an N-doped TiO2-coated Al2O3
      photocatalytic membrane, using different water types. The photocatalytic membrane
      combines photocatalysis and membrane filtration in a single step. The impact of
      each individual constituent such as acidity, alkalinity, dissolved organic matter
      (DOM), divalent cations (Mg2+ and Ca2+), and Cl- on the degradation of CBZ was
      examined. CBZ in water was efficiently degraded by an N-doped TiO2-coated Al2O3
      membrane. However, elements added to the water, which simulate the constituents
      of natural water, had an impact on the CBZ degradation. Water alkalinity
      inhibited CBZ degradation mostly due to increase in pH while radical scavenging
      by carbonate was more dominant at higher values (>200 mg/L as CaCO3). A negative
      effect of Ca2+ addition on photocatalytic degradation was found only in
      combination with phosphate buffer, probably caused by deposition of CaHPO4 or
      CaHPO4.2H2O on the catalyst surface. The presence of Cl- and Mg2+ ions had no
      effect on CBZ degradation. DOM significantly inhibited CBZ degradation for all
      tested background organic compounds. The photocatalytic activity of N-doped TiO2
      coated Al2O3 membranes gradually decreased after continuous use; however, it was
      successfully regenerated by 0.1% HCl chemical cleaning. Nevertheless, dissolution
      of metals like Al and Ti should be monitored following acid cleaning.

PMID- 28758984
TI  - Assessment of Chlorophyll-a Algorithms Considering Different Trophic Statuses and
      Optimal Bands.
AB  - Numerous algorithms have been proposed to retrieve chlorophyll-a concentrations
      in Case 2 waters; however, the retrieval accuracy is far from satisfactory. In
      this research, seven algorithms are assessed with different band combinations of
      multispectral and hyperspectral bands using linear (LN), quadratic polynomial
      (QP) and power (PW) regression approaches, resulting in altogether 43 algorithmic
      combinations. These algorithms are evaluated by using simulated and measured
      datasets to understand the strengths and limitations of these algorithms. Two
      simulated datasets comprising 500,000 reflectance spectra each, both based on
      wide ranges of inherent optical properties (IOPs), are generated for the
      calibration and validation stages. Results reveal that the regression approach
      (i.e., LN, QP, and PW) has more influence on the simulated dataset than on the
      measured one. The algorithms that incorporated linear regression provide the
      highest retrieval accuracy for the simulated dataset. Results from simulated
      datasets reveal that the 3-band (3b) algorithm that incorporate 665-nm and 680-nm
      bands and band tuning selection approach outperformed other algorithms with root
      mean square error (RMSE) of 15.87 mg.m-3, 16.25 mg.m-3, and 19.05 mg.m-3,
      respectively. The spatial distribution of the best performing algorithms, for
      various combinations of chlorophyll-a (Chla) and non-algal particles (NAP)
      concentrations, show that the 3b_tuning_QP and 3b_680_QP outperform other
      algorithms in terms of minimum RMSE frequency of 33.19% and 60.52%, respectively.
      However, the two algorithms failed to accurately retrieve Chla for many
      combinations of Chla and NAP, particularly for low Chla and NAP concentrations.
      In addition, the spatial distribution emphasizes that no single algorithm can
      provide outstanding accuracy for Chla retrieval and that multi-algorithms should
      be included to reduce the error. Comparing the results of the measured and
      simulated datasets reveal that the algorithms that incorporate the 665-nm band
      outperform other algorithms for measured dataset (RMSE = 36.84 mg.m-3), while
      algorithms that incorporate the band tuning approach provide the highest
      retrieval accuracy for the simulated dataset (RMSE = 25.05 mg.m-3).

PMID- 28758985
TI  - Imaging of Subsurface Corrosion Using Gradient-Field Pulsed Eddy Current Probes
      with Uniform Field Excitation.
AB  - A corrosive environment leaves in-service conductive structures prone to
      subsurface corrosion which poses a severe threat to the structural integrity. It
      is indispensable to detect and quantitatively evaluate subsurface corrosion via
      non-destructive evaluation techniques. Although the gradient-field pulsed eddy
      current technique (GPEC) has been found to be superior in the evaluation of
      corrosion in conductors, it suffers from a technical drawback resulting from the
      non-uniform field excited by the conventional pancake coil. In light of this, a
      new GPEC probe with uniform field excitation for the imaging of subsurface
      corrosion is proposed in this paper. The excited uniform field makes the GPEC
      signal correspond only to the field perturbation due to the presence of
      subsurface corrosion, which benefits the corrosion profiling and sizing. A 3D
      analytical model of GPEC is established to analyze the characteristics of the
      uniform field induced within a conductor. Following this, experiments regarding
      the imaging of subsurface corrosion via GPEC have been carried out. It has been
      found from the results that the proposed GPEC probe with uniform field excitation
      not only applies to the imaging of subsurface corrosion in conductive structures,
      but provides high-sensitivity imaging results regarding the corrosion profile and
      opening size.

PMID- 28758986
TI  - Development of Wearable Sheet-Type Shear Force Sensor and Measurement System that
      is Insusceptible to Temperature and Pressure.
AB  - A sheet-type shear force sensor and a measurement system for the sensor were
      developed. The sensor has an original structure where a liquid electrolyte is
      filled in a space composed of two electrode-patterned polymer films and an
      elastic rubber ring. When a shear force is applied on the surface of the sensor,
      the two electrode-patterned films mutually move so that the distance between the
      internal electrodes of the sensor changes, resulting in current increase or
      decrease between the electrodes. Therefore, the shear force can be calculated by
      monitoring the current between the electrodes. Moreover, it is possible to
      measure two-dimensional shear force given that the sensor has multiple
      electrodes. The diameter and thickness of the sensor head were 10 mm and 0.7 mm,
      respectively. Additionally, we also developed a measurement system that drives
      the sensor, corrects the baseline of the raw sensor output, displays data, and
      stores data as a computer file. Though the raw sensor output was considerably
      affected by the surrounding temperature, the influence of temperature was
      drastically decreased by introducing a simple arithmetical calculation. Moreover,
      the influence of pressure simultaneously decreased after the same calculation
      process. A demonstrative measurement using the sensor revealed the practical
      usefulness for on-site monitoring.

PMID- 28758987
TI  - A Framework to Improve Energy Efficient Behaviour at Home through Activity and
      Context Monitoring.
AB  - Real-time Localization Systems have been postulated as one of the most
      appropriated technologies for the development of applications that provide
      customized services. These systems provide us with the ability to locate and
      trace users and, among other features, they help identify behavioural patterns
      and habits. Moreover, the implementation of policies that will foster energy
      saving in homes is a complex task that involves the use of this type of systems.
      Although there are multiple proposals in this area, the implementation of
      frameworks that combine technologies and use Social Computing to influence user
      behaviour have not yet reached any significant savings in terms of energy. In
      this work, the CAFCLA framework (Context-Aware Framework for Collaborative
      Learning Applications) is used to develop a recommendation system for home users.
      The proposed system integrates a Real-Time Localization System and Wireless
      Sensor Networks, making it possible to develop applications that work under the
      umbrella of Social Computing. The implementation of an experimental use case
      aided efficient energy use, achieving savings of 17%. Moreover, the conducted
      case study pointed to the possibility of attaining good energy consumption habits
      in the long term. This can be done thanks to the system's real time and
      historical localization, tracking and contextual data, based on which customized
      recommendations are generated.

PMID- 28758989
TI  - Corrigendum: Palaeo leaf economics reveal a shift in ecosystem function
      associated with the end-Triassic mass extinction event.
AB  - This corrects the article DOI: 10.1038/nplants.2017.104.

PMID- 28758988
TI  - Beneficial Effects of Galectin-3 Blockade in Vascular and Aortic Valve
      Alterations in an Experimental Pressure Overload Model.
AB  - Galectin-3 (Gal-3) is involved in cardiovascular fibrosis and aortic valve (AV)
      calcification. We hypothesized that Gal-3 pharmacological inhibition with
      modified citrus pectin (MCP) could reduce aortic and AV remodeling in
      normotensive rats with pressure overload (PO). Six weeks after aortic
      constriction, vascular Gal-3 expression was up-regulated in male Wistar rats. Gal
      3 overexpression was accompanied by an increase in the aortic media layer
      thickness, enhanced total collagen, and augmented expression of fibrotic
      mediators. Further, vascular inflammatory markers as well as inflammatory cells
      content were greater in aorta from PO rats. MCP treatment (100 mg/kg/day)
      prevented the increase in Gal-3, media thickness, fibrosis, and inflammation in
      the aorta of PO rats. Gal-3 levels were higher in AVs from PO rats. This
      paralleled enhanced AV fibrosis, inflammation, as well as greater expression of
      calcification markers. MCP treatment prevented the increase in Gal-3 as well as
      fibrosis, inflammation, and calcification in AVs. Overall, Gal-3 is overexpressed
      in aorta and AVs from PO rats. Gal-3 pharmacological inhibition blocks aortic and
      AV remodeling in experimental PO. Gal-3 could be a new therapeutic approach to
      delay the progression and the development of aortic remodeling and AV
      calcification in PO.

PMID- 28758991
TI  - Progress and prospects in plant genome editing.
AB  - The emergence of sequence-specific nucleases that enable genome editing is
      revolutionizing basic and applied biology. Since the introduction of CRISPR-Cas9,
      genome editing has become widely used in transformable plants for characterizing
      gene function and improving traits, mainly by inducing mutations through non
      homologous end joining of double-stranded breaks generated by CRISPR-Cas9.
      However, it would be highly desirable to perform precision gene editing in
      plants, especially in transformation-recalcitrant species. Recently developed
      Cas9 variants, novel RNA-guided nucleases and base-editing systems, and DNA-free
      CRISPR-Cas9 delivery methods now provide great opportunities for plant genome
      engineering. In this Review Article, we describe the current status of plant
      genome editing, focusing on newly developed genome editing tools and methods and
      their potential applications in plants. We also discuss the specific challenges
      facing plant genome editing, and future prospects.

PMID- 28758990
TI  - Coordinated regulation of growth, activity and transcription in natural
      populations of the unicellular nitrogen-fixing cyanobacterium Crocosphaera.
AB  - The temporal dynamics of phytoplankton growth and activity have large impacts on
      fluxes of matter and energy, yet obtaining in situ metabolic measurements of
      sufficient resolution for even dominant microorganisms remains a considerable
      challenge. We performed Lagrangian diel sampling with synoptic measurements of
      population abundances, dinitrogen (N2) fixation, mortality, productivity, export
      and transcription in a bloom of Crocosphaera over eight days in the North Pacific
      Subtropical Gyre (NPSG). Quantitative transcriptomic analyses revealed clear diel
      oscillations in transcript abundances for 34% of Crocosphaera genes identified,
      reflecting a systematic progression of gene expression in diverse metabolic
      pathways. Significant time-lagged correspondence was evident between nifH
      transcript abundance and maximal N2 fixation, as well as sepF transcript
      abundance and cell division, demonstrating the utility of transcriptomics to
      predict the occurrence and timing of physiological and biogeochemical processes
      in natural populations. Indirect estimates of carbon fixation by Crocosphaera
      were equivalent to 11% of net community production, suggesting that under bloom
      conditions this diazotroph has a considerable impact on the wider carbon cycle.
      Our cross-scale synthesis of molecular, population and community-wide data
      underscores the tightly coordinated in situ metabolism of the keystone N2-fixing
      cyanobacterium Crocosphaera, as well as the broader ecosystem-wide implications
      of its activities.

PMID- 28758992
TI  - Demystifying traditional herbal medicine with modern approach.
AB  - Plants have long been recognized for their therapeutic properties. For centuries,
      indigenous cultures around the world have used traditional herbal medicine to
      treat a myriad of maladies. By contrast, the rise of the modern pharmaceutical
      industry in the past century has been based on exploiting individual active
      compounds with precise modes of action. This surge has yielded highly effective
      drugs that are widely used in the clinic, including many plant natural products
      and analogues derived from these products, but has fallen short of delivering
      effective cures for complex human diseases with complicated causes, such as
      cancer, diabetes, autoimmune disorders and degenerative diseases. While the plant
      kingdom continues to serve as an important source for chemical entities
      supporting drug discovery, the rich traditions of herbal medicine developed by
      trial and error on human subjects over thousands of years contain invaluable
      biomedical information just waiting to be uncovered using modern scientific
      approaches. Here we provide an evolutionary and historical perspective on why
      plants are of particular significance as medicines for humans. We highlight
      several plant natural products that are either in the clinic or currently under
      active research and clinical development, with particular emphasis on their
      mechanisms of action. Recent efforts in developing modern multi-herb
      prescriptions through rigorous molecular-level investigations and standardized
      clinical trials are also discussed. Emerging technologies, such as genomics and
      synthetic biology, are enabling new ways for discovering and utilizing the
      medicinal properties of plants. We are entering an exciting era where the ancient
      wisdom distilled into the world's traditional herbal medicines can be
      reinterpreted and exploited through the lens of modern science.

PMID- 28758993
TI  - Palaeobotany: New ways with old fossils.

PMID- 28758994
TI  - High-dimensional, single-cell characterization of the brain's immune compartment.
AB  - The brain and its borders create a highly dynamic microenvironment populated with
      immune cells. Yet characterization of immune cells within the naive brain
      compartment remains limited. In this study, we used CyTOF mass cytometry to
      characterize the immune populations of the naive mouse brain using 44 cell
      surface markers. By comparing immune cell composition and cell profiles between
      the brain compartment and blood, we were able to characterize previously
      undescribed cell subsets of CD8 T cells, B cells, NK cells and dendritic cells in
      the naive brain. Using flow cytometry, we show differential distributions of
      immune populations between meninges, choroid plexus and parenchyma. We
      demonstrate the phenotypic ranges of resident myeloid cells and identify CD44 as
      a marker for infiltrating immune populations. This study provides an approach for
      a system-wide view of immune populations in the brain and is expected to serve as
      a resource for understanding brain immunity.

PMID- 28758995
TI  - Dorsal hippocampus contributes to model-based planning.
AB  - Planning can be defined as action selection that leverages an internal model of
      the outcomes likely to follow each possible action. Its neural mechanisms remain
      poorly understood. Here we adapt recent advances from human research for rats,
      presenting for the first time an animal task that produces many trials of planned
      behavior per session, making multitrial rodent experimental tools available to
      study planning. We use part of this toolkit to address a perennially
      controversial issue in planning: the role of the dorsal hippocampus. Although
      prospective hippocampal representations have been proposed to support planning,
      intact planning in animals with damaged hippocampi has been repeatedly observed.
      Combining formal algorithmic behavioral analysis with muscimol inactivation, we
      provide causal evidence directly linking dorsal hippocampus with planning
      behavior. Our results and methods open the door to new and more detailed
      investigations of the neural mechanisms of planning in the hippocampus and
      throughout the brain.

PMID- 28758996
TI  - Adults with autism overestimate the volatility of the sensory environment.
AB  - Insistence on sameness and intolerance of change are among the diagnostic
      criteria for autism spectrum disorder (ASD), but little research has addressed
      how people with ASD represent and respond to environmental change. Here,
      behavioral and pupillometric measurements indicated that adults with ASD are less
      surprised than neurotypical adults when their expectations are violated, and
      decreased surprise is predictive of greater symptom severity. A hierarchical
      Bayesian model of learning suggested that in ASD, a tendency to overlearn about
      volatility in the face of environmental change drives a corresponding reduction
      in learning about probabilistically aberrant events, thus putatively rendering
      these events less surprising. Participant-specific modeled estimates of surprise
      about environmental conditions were linked to pupil size in the ASD group, thus
      suggesting heightened noradrenergic responsivity in line with compromised neural
      gain. This study offers insights into the behavioral, algorithmic and
      physiological mechanisms underlying responses to environmental volatility in ASD.

PMID- 28758997
TI  - Zika virus directly infects peripheral neurons and induces cell death.
AB  - Zika virus (ZIKV) infection is associated with neurological disorders of both the
      CNS and peripheral nervous systems (PNS), yet few studies have directly examined
      PNS infection. Here we show that intraperitoneally or intraventricularly injected
      ZIKV in the mouse can infect and impact peripheral neurons in vivo. Moreover,
      ZIKV productively infects stem-cell-derived human neural crest cells and
      peripheral neurons in vitro, leading to increased cell death, transcriptional
      dysregulation and cell-type-specific molecular pathology.

PMID- 28758998
TI  - Functional dissection of signal and noise in MT and LIP during decision-making.
AB  - During perceptual decision-making, responses in the middle temporal (MT) and
      lateral intraparietal (LIP) areas appear to map onto theoretically defined
      quantities, with MT representing instantaneous motion evidence and LIP reflecting
      the accumulated evidence. However, several aspects of the transformation between
      the two areas have not been empirically tested. We therefore performed multistage
      systems identification analyses of the simultaneous activity of MT and LIP during
      individual decisions. We found that monkeys based their choices on evidence
      presented in early epochs of the motion stimulus and that substantial early
      weighting of motion was present in MT responses. LIP responses recapitulated MT
      early weighting and contained a choice-dependent buildup that was distinguishable
      from motion integration. Furthermore, trial-by-trial variability in LIP did not
      depend on MT activity. These results identify important deviations from
      idealizations of MT and LIP and motivate inquiry into sensorimotor computations
      that may intervene between MT and LIP.

PMID- 28759000
TI  - Starch synthesis: Seeding the pearl.

PMID- 28758999
TI  - Necroptosis activation in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by severe neuronal loss; however, the
      mechanisms by which neurons die remain elusive. Necroptosis, a programmed form of
      necrosis, is executed by the mixed lineage kinase domain-like (MLKL) protein,
      which is triggered by receptor-interactive protein kinases (RIPK) 1 and 3. We
      found that necroptosis was activated in postmortem human AD brains, positively
      correlated with Braak stage, and inversely correlated with brain weight and
      cognitive scores. In addition, we found that the set of genes regulated by RIPK1
      overlapped significantly with multiple independent AD transcriptomic signatures,
      indicating that RIPK1 activity could explain a substantial portion of
      transcriptomic changes in AD. Furthermore, we observed that lowering necroptosis
      activation reduced cell loss in a mouse model of AD. We anticipate that our
      findings will spur a new area of research in the AD field focused on developing
      new therapeutic strategies aimed at blocking its activation.

PMID- 28759001
TI  - Tumor immunoevasion by the conversion of effector NK cells into type 1 innate
      lymphoid cells.
AB  - Avoiding destruction by immune cells is a hallmark of cancer, yet how tumors
      ultimately evade control by natural killer (NK) cells remains incompletely
      defined. Using global transcriptomic and flow-cytometry analyses and genetically
      engineered mouse models, we identified the cytokine-TGF-beta-signaling-dependent
      conversion of NK cells (CD49a-CD49b+Eomes+) into intermediate type 1 innate
      lymphoid cell (intILC1) (CD49a+CD49b+Eomes+) populations and ILC1 (CD49a+CD49b
      Eomesint) populations in the tumor microenvironment. Strikingly, intILC1s and
      ILC1s were unable to control local tumor growth and metastasis, whereas NK cells
      favored tumor immunosurveillance. Experiments with an antibody that neutralizes
      the cytokine TNF suggested that escape from the innate immune system was
      partially mediated by TNF-producing ILC1s. Our findings provide new insight into
      the plasticity of group 1 ILCs in the tumor microenvironment and suggest that the
      TGF-beta-driven conversion of NK cells into ILC1s is a previously unknown
      mechanism by which tumors escape surveillance by the innate immune system.

PMID- 28759002
TI  - SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non
      canonical TGF-beta signaling.
AB  - Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from
      natural killer (NK) cells is a gene signature indicative of 'imprinting' by
      cytokines of the TGF-beta family. We studied mice in which ILC1s and NK cells
      lacked SMAD4, a signal transducer that facilitates the canonical signaling
      pathway common to all cytokines of the TGF-beta family. While SMAD4 deficiency
      did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like
      gene signature and were unable to control tumor metastasis or viral infection.
      Mechanistically, SMAD4 restrained non-canonical TGF-beta signaling mediated by
      the cytokine receptor TGFbetaR1 in NK cells. NK cells from a SMAD4-deficient
      person affected by polyposis were also hyper-responsive to TGF-beta. These
      results identify SMAD4 as a previously unknown regulator that restricts non
      canonical TGF-beta signaling in NK cells.

PMID- 28759003
TI  - MLL4 prepares the enhancer landscape for Foxp3 induction via chromatin looping.
AB  - MLL4 is an essential subunit of the histone H3 Lys4 (H3K4)-methylation complexes.
      We found that MLL4 deficiency compromised the development of regulatory T cells
      (Treg cells) and resulted in a substantial decrease in monomethylated H3K4
      (H3K4me1) and chromatin interaction at putative gene enhancers, a considerable
      portion of which were not direct targets of MLL4 but were enhancers that
      interacted with MLL4-bound sites. The decrease in H3K4me1 and chromatin
      interaction at the enhancers not bound by MLL4 correlated with MLL4 binding at
      distant interacting regions. Deletion of an upstream MLL4-binding site diminished
      the abundance of H3K4me1 at the regulatory elements of the gene encoding the
      transcription factor Foxp3 that were looped to the MLL4-binding site and
      compromised both the thymic differentiation and the inducible differentiation of
      Treg cells. We found that MLL4 catalyzed methylation of H3K4 at distant unbound
      enhancers via chromatin looping, which identifies a previously unknown mechanism
      for regulating the T cell enhancer landscape and affecting Treg cell
      differentiation.

PMID- 28759004
TI  - A common intronic variant of PARP1 confers melanoma risk and mediates melanocyte
      growth via regulation of MITF.
AB  - Previous genome-wide association studies have identified a melanoma-associated
      locus at 1q42.1 that encompasses a ~100-kb region spanning the PARP1 gene.
      Expression quantitative trait locus (eQTL) analysis in multiple cell types of the
      melanocytic lineage consistently demonstrated that the 1q42.1 melanoma risk
      allele (rs3219090[G]) is correlated with higher PARP1 levels. In silico fine
      mapping and functional validation identified a common intronic indel, rs144361550
      (-/GGGCCC; r2 = 0.947 with rs3219090), as displaying allele-specific
      transcriptional activity. A proteomic screen identified RECQL as binding to
      rs144361550 in an allele-preferential manner. In human primary melanocytes, PARP1
      promoted cell proliferation and rescued BRAFV600E-induced senescence phenotypes
      in a PARylation-independent manner. PARP1 also transformed TERT-immortalized
      melanocytes expressing BRAFV600E. PARP1-mediated senescence rescue was
      accompanied by transcriptional activation of the melanocyte-lineage survival
      oncogene MITF, highlighting a new role for PARP1 in melanomagenesis.

PMID- 28759005
TI  - Bayesian analysis of genetic association across tree-structured routine
      healthcare data in the UK Biobank.
AB  - Genetic discovery from the multitude of phenotypes extractable from routine
      healthcare data can transform understanding of the human phenome and accelerate
      progress toward precision medicine. However, a critical question when analyzing
      high-dimensional and heterogeneous data is how best to interrogate increasingly
      specific subphenotypes while retaining statistical power to detect genetic
      associations. Here we develop and employ a new Bayesian analysis framework that
      exploits the hierarchical structure of diagnosis classifications to analyze
      genetic variants against UK Biobank disease phenotypes derived from self
      reporting and hospital episode statistics. Our method displays a more than 20%
      increase in power to detect genetic effects over other approaches and identifies
      new associations between classical human leukocyte antigen (HLA) alleles and
      common immune-mediated diseases (IMDs). By applying the approach to genetic risk
      scores (GRSs), we show the extent of genetic sharing among IMDs and expose
      differences in disease perception or diagnosis with potential clinical
      implications.

PMID- 28759006
TI  - Re-expression of Sall1 in podocytes protects against adriamycin-induced
      nephrosis.
AB  - The highly conserved spalt (sal) gene family members encode proteins
      characterized by multiple double zinc finger motifs of the C2H2 type. Humans and
      mice each have four known Sal-like genes (SALL1-4 in humans and Sall1-4 in mice).
      Sall1 is known to have a crucial role in kidney development. To explore the
      significance of Sall1 in differentiated podocytes, we investigated podocyte
      specific Sall1-deficient mice (Sall1 KOp degrees d degrees /p degrees d degrees )
      using a podocin-Cre/loxP system and siRNA Sall1 knockdown (Sall1 KD) podocytes.
      Under physiological conditions, Sall1 KOp degrees d degrees /p degrees d degrees 
      mice exhibited no proteinuria during their lifetime, but foot-process effacement
      was detected in some of the podocytes. To elucidate the role of Sall1 in injured
      podocytes, we used an adriamycin (ADR)-induced model of nephrosis and
      glomerulosclerosis. Surprisingly, the expression of Sall1 was elevated in control
      mice on day 14 after ADR injection. On day 28 after ADR injection, Sall1 KOp
      degrees d degrees /p degrees d degrees  mice exhibited significantly higher
      levels of proteinuria and higher numbers of sclerotic glomeruli. Differentiated
      Sall1 KD podocytes showed a loss of synaptopodin, suppressed stress fiber
      formation, and, ultimately, impaired directed cell migration. In addition, the
      loss of Sall1 increased the number of apoptotic podocytes following ADR
      treatment. These results indicated that Sall1 has a protective role in podocytes;
      thus, we investigated the endoplasmic reticulum stress marker GRP78. GRP78
      expression was higher in ADR-treated Sall1 KOp degrees d degrees /p degrees d
      degrees  mice than in control mice. Sall1 appeared to influence the expression of
      GRP78 in injured podocytes. These results suggest that Sall1 is associated with
      actin reorganization, endoplasmic reticulum stress, and apoptosis in injured
      podocytes. These protective aspects of Sall1 re-expression in injured podocytes
      may have the potential to reduce apoptosis and possibly glomerulosclerosis.

PMID- 28759007
TI  - Generating diversity in human glucocorticoid signaling through a racially diverse
      polymorphism in the beta isoform of the glucocorticoid receptor.
AB  - Alternative splicing of the human glucocorticoid receptor gene generates two
      isoforms, hGRalpha and hGRbeta. hGRbeta functions as a dominant-negative
      regulator of hGRalpha activity and but also has inherent transcriptional
      activity, collectively altering glucocorticoid sensitivity. Single-nucleotide
      polymorphisms in the 3' UTR of hGRbeta have been associated with altered receptor
      protein expression, glucocorticoid sensitivity, and disease risk.
      Characterization of the hGRbeta G3134T polymorphism has been limited to a
      relatively small, homogenous population. The objective of this study was to
      determine the prevalence of hGRbeta G3134T in a diverse population and assess the
      association of hGRbeta G3134T in this population with physiological outcomes. In
      a prospective cohort study, 3730 genetically diverse participants were genotyped
      for hGRbeta G3134T and four common GR polymorphisms. A subset of these
      participants was evaluated for clinical and biochemical measurements.
      Immortalized human osteosarcoma cells (U-2 OS), stably transfected with wild-type
      or G3134T hGRbeta, were evaluated for receptor expression, stability, and genome
      wide gene expression. Glucocorticoid-mediated gene expression profiles were
      investigated in primary macrophages isolated from participants. In a racially
      diverse population, the minor allele frequency was 74% (50.7% heterozygous
      carriers and 23.3% homozygous minor allele), with a higher prevalence in
      Caucasian non-Hispanic participants. After adjusting for confounding variable,
      carriers of hGRbeta G3134T were more likely to self-report allergies, have higher
      serum cortisol levels, and reduced cortisol suppression in response to low-dose
      dexamethasone. The presence of hGRbeta G3134T in U-2 OS cells increased hGR mRNA
      stability and protein expression. Microarray analysis revealed that the presence
      of the hGRbeta G3134T polymorphism uniquely altered gene expression profiles in U
      2 OS cells and primary macrophages. hGRbeta G3134T is significantly present in
      the study population and associated with race, self-reported disease, and serum
      levels of glucocorticoids. Underlying these health differences may be changes in
      gene expression driven by altered receptor stability.

PMID- 28759008
TI  - A pathologist's perspective on induced pluripotent stem cells.
AB  - Induced pluripotent stem cell (iPSC) technology was originally developed in 2006.
      Essentially, it converts somatic cells into pluripotent stem cells by transiently
      expressing a few transcriptional factors. Once generated, these iPSCs can
      differentiate into all the cell types of our body, theoretically, which has
      attracted great attention for clinical research including disease pathobiology
      studies. Could this technology then become an additional research or diagnostic
      tool widely available to practicing pathologists? Here we summarize progress in
      iPSC research toward disease pathobiology studies, its future potential, and
      remaining problems from a pathologist's perspective. A particular focus will be
      on introducing the effort to recapitulate disease-related morphological changes
      through three-dimensional culture of stem cells such as organoid differentiation.

PMID- 28759009
TI  - Ginseng extract reduces tacrolimus-induced oxidative stress by modulating
      autophagy in pancreatic beta cells.
AB  - We previously reported that long-term treatment with a calcineurin inhibitor
      impairs autophagy process in pancreatic beta cells. This study investigated the
      effect of Korean red ginseng extract (KRGE) on autophagy modulated by oxidative
      stress. In mice with tacrolimus (Tac)-induced diabetes mellitus, KRGE alleviated
      islet dysfunction and decreased oxidative stress and autophagic vacuoles. In
      vitro, KRGE decreased autophagosome formation and attenuated lysosomal
      degradation, accompanied by improved beta cell viability and insulin secretion.
      Addition of 3-methyladenine (3-MA), an inhibitor of autophagosomes, to KRGE
      further improved cell viability and insulin secretion, and bafilomycin A (BA), an
      inhibitor of lysosomal function, reduced the effects of KRGE. At the subcellular
      level, Tac caused mitochondrial dysfunction (impaired mitochondrial oxygen
      consumption, ATP production, and increased reactive oxygen species production).
      But KRGE improved these parameters. The effect of KRGE on mitochondrial function
      enhanced by 3-MA but decreased by BA, suggesting a causal relationship between
      KRGE effect and autophagy modulation in Tac-induced mitochondrial dysfunction.
      These findings indicate that KRGE modulates autophagy favorably by reducing Tac
      induced oxidative stress, and this effect is closely associated with improvement
      of mitochondrial function.

PMID- 28759010
TI  - Establishment and long-term culture of human cystic fibrosis endothelial cells.
AB  - Endothelial cell (EC) dysfunction has been reported in cystic fibrosis (CF)
      patients. Thus, the availability of CF EC is paramount to uncover mechanisms of
      endothelial dysfunction in CF. Using collagenase digestion, we isolated cells
      from small fragments of pulmonary artery dissected from non-CF lobes or explanted
      CF lungs. These cells were a heterogeneous mixture, containing variable
      percentages of EC. To obtain virtually pure pulmonary artery endothelial cells
      (PAEC), we developed an easy, inexpensive, and reliable method, based on the
      differential adhesion time of pulmonary artery cells collected after collagenase
      digestion. With this method, we obtained up to 95% pure non-CF and CF-PAEC.
      Moreover, we also succeed at immortalizing both PAEC and CF-PAEC, which remained
      viable and with unchanged phenotype and proliferation rate over the 30th passage.
      These cells recapitulated cystic fibrosis transmembrane conductance regulator
      expression and functions of the parental cells. Thus, we isolated for the first
      time endothelial cells from CF patients, providing a valuable tool to define the
      emerging role of EC in CF lung and vascular disease.

PMID- 28759011
TI  - Phosphorylated mTOR and YAP serve as prognostic markers and therapeutic targets
      in gliomas.
AB  - Glioma is the most prevalent type of tumor in the brain and is comprised of
      grades I-IV, according to the WHO classification system. Grade IV glioma is also
      known as glioblastoma multiforme (GBM), the most malignant type of glioma. Glioma
      is characterized by a complex molecular background, and gene profiling studies
      have disclosed critical genetic events in human gliomas, which make targeted
      therapies the most promising therapeutic strategy. However, crosstalk between the
      targeted signaling pathways may hinder the efficacy of targeted therapies in
      gliomas. Therefore, it is necessary to identify effective markers to stratify
      patients for specific therapeutic procedures. Although several mechanisms have
      been proposed based on the crosstalk between PI3K/AKT/mTORC1 and Hippo/YAP
      pathways, the clinical significance of the two pathways has not yet been assessed
      in a combinatorial manner. In this study, we evaluated the two pathways in human
      glioma specimens and observed the positive correlation between protein levels of
      p-mTORS2448 and YAP in gliomas. The findings indicated that high expression of p
      mTORS2448 and YAP correlated with poor overall survival of glioma patients. As p
      mTORS2448 is a specific marker of mTORC1 activation, our results reveal a
      potential interaction between mTORC1 and YAP, which might functionally
      participate in the development and progression of gliomas. In support of this
      hypothesis, a combination of inhibitors targeting mTORC1 and YAP showed a better
      inhibitory effect on growth of glioma cell lines. Altogether, our work, for the
      first time, reveals that p-mTORS2448 and YAP can be used as markers of
      PI3K/AKT/mTORC1 and Hippo/YAP pathway activity to predict prognosis and are
      target candidates for personalized medicine.

PMID- 28759012
TI  - Berberine inhibits colitis-associated tumorigenesis via suppressing inflammatory
      responses and the consequent EGFR signaling-involved tumor cell growth.
AB  - The anti-inflammatory and anti-tumor effects of berberine, a traditional Chinese
      medicine, were separately discovered in pathological intestinal tissues. However,
      whether the anti-inflammatory effect of berberine contributes to its anti-tumor
      effect on colitis-associated colorectal cancer (CACRC) remains unknown. In the
      present study, we found that berberine effectively inhibited colitis-associated
      tumorigenesis and colonic epithelium hyperproliferation in dextran sulfate sodium
      (DSS)-treated ApcMin/+ mice. A mechanistic study identified that these inhibitory
      effects of berberine occurred through blocking interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) expression in colonic macrophages. An in vitro
      study on cell lines identified that berberine treatment of Raw 264.7 macrophages
      resulted in conditioned media with fewer proliferative effects on a cell line
      with a heterozygous Apc mutation (Immorto-Min colonic epithelium, IMCE). EGFR-ERK
      signaling act downstream of berberine/pro-inflammatory cytokines axis to regulate
      CACRC cell proliferation. Furthermore, in vivo administration of IL-6 to DSS
      treated ApcMin/+ mice effectively weakened the inhibitory effects of berberine on
      tumorigenesis and EGFR-ERK signaling in colon tissues. Altogether, the results of
      our studies have revealed that berberine inhibits the development of CACRC by
      interfering with inflammatory response-driven EGFR signaling in tumor cell
      growth. The findings of this study support the possibility that berberine and
      other anti-inflammatory drugs may be beneficial in the treatment of CACRC.

PMID- 28759013
TI  - Papillary renal cell carcinoma-derived chemerin, IL-8, and CXCL16 promote
      monocyte recruitment and differentiation into foam-cell macrophages.
AB  - Papillary renal cell carcinoma (pRCC) is the second most common type of renal
      cell carcinoma. The only curative treatment available for pRCC is radical
      surgery. If the disease becomes widespread, neither chemo- nor radiotherapy will
      have therapeutic effect, hence further research on pRCC is of utmost importance.
      Histologically, pRCC is characterized by a papillary growth pattern with focal
      aggregation of macrophages of the foam cell phenotype. In other forms of cancer,
      a clear role for tumor-associated macrophages during cancer growth and
      progression has been shown. Although the presence of foamy macrophages is a
      histological hallmark of pRCC tumors, little is known regarding their role in
      pRCC biology. In order to study the interaction between pRCC tumor and myeloid
      cells, we established primary cultures from pRCC tissue. We show that human pRCC
      cells secrete the chemokines IL-8, CXCL16, and chemerin, and that these factors
      attract primary human monocytes in vitro. RNAseq data from The Cancer Genome
      Atlas confirmed a high expression of these factors in pRCC tissue. Conditioned
      medium from pRCC cultures induced a shift in human monocytes toward the M2
      macrophage phenotype. In extended cultures, these macrophages became enlarged and
      loaded with lipids, adopting the foam cell morphology found in pRCC tissue. These
      results show for the first time that pRCC primary tumor cells secrete factors
      that attract and differentiate monocytes into anti-inflammatory tumor-associated
      macrophages with foam cell histology.

PMID- 28759014
TI  - Functional annotation of chemical libraries across diverse biological processes.
AB  - Chemical-genetic approaches offer the potential for unbiased functional
      annotation of chemical libraries. Mutations can alter the response of cells in
      the presence of a compound, revealing chemical-genetic interactions that can
      elucidate a compound's mode of action. We developed a highly parallel, unbiased
      yeast chemical-genetic screening system involving three key components. First, in
      a drug-sensitive genetic background, we constructed an optimized diagnostic
      mutant collection that is predictive for all major yeast biological processes.
      Second, we implemented a multiplexed (768-plex) barcode-sequencing protocol,
      enabling the assembly of thousands of chemical-genetic profiles. Finally, based
      on comparison of the chemical-genetic profiles with a compendium of genome-wide
      genetic interaction profiles, we predicted compound functionality. Applying this
      high-throughput approach, we screened seven different compound libraries and
      annotated their functional diversity. We further validated biological process
      predictions, prioritized a diverse set of compounds, and identified compounds
      that appear to have dual modes of action.

PMID- 28759015
TI  - Peptidomimetic inhibitors of APC-Asef interaction block colorectal cancer
      migration.
AB  - The binding of adenomatous polyposis coli (APC) to its receptor Asef relieves the
      negative intramolecular regulation of Asef and leads to aberrant cell migration
      in human colorectal cancer. Because of its crucial role in metastatic
      dissemination, the interaction between APC and Asef is an attractive target for
      anti-colorectal-cancer therapy. We rationally designed a series of
      peptidomimetics that act as potent inhibitors of the APC interface. Crystal
      structures and biochemical and cellular assays showed that the peptidomimetics in
      the APC pocket inhibited the migration of colorectal cells by disrupting APC-Asef
      interaction. By using the peptidomimetic inhibitor as a chemical probe, we found
      that CDC42 was the downstream GTPase involved in APC-stimulated Asef activation
      in colorectal cancer cells. Our work demonstrates the feasibility of exploiting
      APC-Asef interaction to regulate the migration of colorectal cancer cells, and
      provides what to our knowledge is the first class of protein-protein interaction
      inhibitors available for the development of cancer therapeutics targeting APC
      Asef signaling.

PMID- 28759016
TI  - Molecular basis for the unusual ring reconstruction in fungal meroterpenoid
      biogenesis.
AB  - Trt14 from Aspergillus terreus is involved in unusual skeletal reconstruction
      during the biosynthesis of the fungal meroterpenoid terretonin. Detailed in vitro
      characterization revealed that this novel multifunctional enzyme catalyzes not
      only the D-ring expansion via intramolecular methoxy rearrangement, but also the
      hydrolysis of the expanded D-ring. The X-ray crystal structures of Trt14, in
      complex with substrate or product, and two Trt14 homologs, AusH and PrhC from
      Aspergillus nidulans and Penicillium brasilianum, respectively, indicated similar
      overall structures to those of the NTF2-like superfamily of enzymes, despite
      lacking sequence and functional similarities. Moreover, we gained structural
      insight into the mechanism of the Trt14-catalyzed ring reconstruction from the in
      crystal enzyme reaction and site-directed mutagenesis to show that this reaction
      involves sequential ester bond cleavage and formation. Structural comparison of
      Trt14 and its homologs suggests that the enzymes in this new superfamily employ
      similar acid-base chemistry to diversify the molecular architecture of fungal
      meroterpenoids.

PMID- 28759017
TI  - FRET monitoring of a nonribosomal peptide synthetase.
AB  - Nonribosomal peptide synthetases (NRPSs) are multidomain enzyme templates for the
      synthesis of bioactive peptides. Large-scale conformational changes during
      peptide assembly are obvious from crystal structures, yet their dynamics and
      coupling to catalysis are poorly understood. We have designed an NRPS FRET sensor
      to monitor, in solution and in real time, the adoption of the productive transfer
      conformation between phenylalanine-binding adenylation (A) and peptidyl-carrier
      protein domains of gramicidin synthetase I from Aneurinibacillus migulanus. The
      presence of ligands, substrates or intermediates induced a distinct fluorescence
      resonance energy transfer (FRET) readout, which was pinpointed to the population
      of specific conformations or, in two cases, mixtures of conformations. A
      pyrophosphate switch and lysine charge sensors control the domain alternation of
      the A domain. The phenylalanine-thioester and phenylalanine-AMP products
      constitute a mechanism of product inhibition and release that is involved in
      ordered assembly-line peptide biosynthesis. Our results represent insights from
      solution measurements into the conformational dynamics of the catalytic cycle of
      NRPSs.

PMID- 28759018
TI  - Toxicity and repair of DNA adducts produced by the natural product yatakemycin.
AB  - Yatakemycin (YTM) is an extraordinarily toxic DNA alkylating agent with potent
      antimicrobial and antitumor properties and is the most recent addition to the CC
      1065 and duocarmycin family of natural products. Though bulky DNA lesions the
      size of those produced by YTM are normally removed from the genome by the
      nucleotide-excision repair (NER) pathway, YTM adducts are also a substrate for
      the bacterial DNA glycosylases AlkD and YtkR2, unexpectedly implicating base
      excision repair (BER) in their elimination. The reason for the extreme toxicity
      of these lesions and the molecular basis for the way they are eliminated by BER
      have been unclear. Here, we describe the structural and biochemical properties of
      YTM adducts that are responsible for their toxicity, and define the mechanism by
      which they are excised by AlkD. These findings delineate an alternative strategy
      for repair of bulky DNA damage and establish the cellular utility of this pathway
      relative to that of NER.

PMID- 28759019
TI  - Copper import in Escherichia coli by the yersiniabactin metallophore system.
AB  - Copper plays a dual role as a nutrient and a toxin during bacterial infections.
      While uropathogenic Escherichia coli (UPEC) strains can use the copper-binding
      metallophore yersiniabactin (Ybt) to resist copper toxicity, Ybt also converts
      bioavailable copper to Cu(II)-Ybt in low-copper conditions. Although E. coli have
      long been considered to lack a copper import pathway, we observed Ybt-mediated
      copper import in UPEC using canonical Fe(III)-Ybt transport proteins. UPEC
      removed copper from Cu(II)-Ybt with subsequent re-export of metal-free Ybt to the
      extracellular space. Copper released through this process became available to an
      E. coli cuproenzyme (the amine oxidase TynA), linking this import pathway to a
      nutrient acquisition function. Ybt-expressing E. coli thus engage in nutritional
      passivation, a strategy of minimizing a metal ion's toxicity while preserving its
      nutritional availability. Copper acquisition through this process may contribute
      to the marked virulence defect of Ybt-transport-deficient UPEC.

PMID- 28759020
TI  - Modulating the DNA polymerase beta reaction equilibrium to dissect the reverse
      reaction.
AB  - DNA polymerases catalyze efficient and high-fidelity DNA synthesis. While this
      reaction favors nucleotide incorporation, polymerases also catalyze a reverse
      reaction, pyrophosphorolysis, that removes the DNA primer terminus and generates
      deoxynucleoside triphosphates. Because pyrophosphorolysis can influence
      polymerase fidelity and sensitivity to chain-terminating nucleosides, we analyzed
      pyrophosphorolysis with human DNA polymerase beta and found the reaction to be
      inefficient. The lack of a thio-elemental effect indicated that this reaction was
      limited by a nonchemical step. Use of a pyrophosphate analog, in which the
      bridging oxygen is replaced with an imido group (PNP), increased the rate of the
      reverse reaction and displayed a large thio-elemental effect, indicating that
      chemistry was now rate determining. Time-lapse crystallography with PNP captured
      structures consistent with a chemical equilibrium favoring the reverse reaction.
      These results highlight the importance of the bridging atom between the beta- and
      gamma-phosphates of the incoming nucleotide in reaction chemistry, enzyme
      conformational changes, and overall reaction equilibrium.

PMID- 28759021
TI  - ASCT2 regulates glutamine uptake and cell growth in endometrial carcinoma.
AB  - Glutamine commonly becomes a conditionally essential amino acid in cancer.
      Glutamine is supplied to the cell by transporters such as ASCT2 (SLC1A5), which
      is frequently upregulated in multiple cancers. Here we investigated the
      expression of ASCT2 in endometrial carcinoma, and evaluated the contribution of
      ASCT2 to glutamine uptake and endometrial cancer cell growth. Analysis of human
      gene expression data showed that ASCT2 was significantly upregulated in both
      endometrioid and serous subtypes of endometrial carcinoma, compared to normal,
      age-matched endometrium. Furthermore, immunohistochemical staining of primary
      human endometrioid adenocarcinomas showed that tumours stain positive for ASCT2
      in either a uniform or mosaic expression pattern, while normal adjacent glands
      appeared predominantly negative for ASCT2 staining. Chemical inhibition of
      glutamine transport by benzylserine or GPNA led to a significant decrease in
      endometrial cancer cell growth and spheroid cross-sectional area. ASCT2 knockdown
      recapitulated the decrease of cell growth and spheroid cross-sectional area in
      HEC1A cells, suggesting a reliance on ASCT2-mediated glutamine uptake. ASCT2
      knockdown in Ishikawa cells led to lower glutamine uptake and cell growth, but
      did not affect spheroid area. Ishikawa cells express higher levels of the
      glutamine transporter SNAT1 compared to HEC1A cells, suggesting these cells may
      rely on both ASCT2 and SNAT1 for glutamine uptake. Since SNAT1 is also
      significantly upregulated in the endometrioid and serous subtypes, these data
      indicate that ASCT2 and SNAT1 could be used as markers of malignancy, and/or
      potential therapeutic targets in patients with endometrial carcinoma.

PMID- 28759022
TI  - miR-151a induces partial EMT by regulating E-cadherin in NSCLC cells.
AB  - miR-151a and its host gene, focal adhesion kinase, FAK, are located in a region
      of chromosome 8q that is frequently amplified in solid tumors, including lung
      cancer. Lung cancer is the leading cause of cancer deaths worldwide and
      metastasis remains the major challenge in battling lung cancer mortality. Here,
      we demonstrate that miR-151a is overexpressed in non-small cell lung cancer
      (NSCLC) patient specimens, as compared to healthy lung. In addition, miR-151a
      overexpression promotes proliferation, epithelial-to-mesenchymal transition (EMT)
      and induces tumor cell migration and invasion of NSCLC cells. Blocking miR-151a
      expression using anti-miR-151a approaches significantly reduced NCSLC cell
      proliferative and motility potential. Furthermore, we determined that miR-151a
      significantly regulates E-cadherin expression. Finally, functional rescue
      experiments determined that overexpression of E-cadherin in miR-151a NSCLC cell
      lines potently repressed miR-151a-induced partial EMT and cell migration of NSCLC
      cells. In conclusion, our findings suggest that miR-151a functions as an oncomiR
      in NSCLC by targeting E-cadherin mRNA and inducing proliferation, migration and
      partial EMT.

PMID- 28759023
TI  - MeCP2, a target of miR-638, facilitates gastric cancer cell proliferation through
      activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1.
AB  - Methyl-CpG binding protein 2 (MeCP2) is involved in the carcinogenesis and
      progression of multiple types of cancer. However, its precise role in gastric
      cancer (GC) and the relevant molecular mechanism remain unknown. In the present
      study, we found that miR-638 levels were lower in GC tissues and GC cell lines
      than in adjacent normal tissues and normal gastric epithelial cell lines,
      respectively. Low miR-638 levels were associated with poor tumor differentiation,
      tumor size and lymph node metastasis. MeCP2 expression levels were higher in GC
      tissues than in adjacent normal tissues. It was found that miR-638 inhibited GC
      cell proliferation, colony formation, G1-S transition and tumor growth, and
      induced cell apoptosis by directly targeting MeCP2. MeCP2 promoted GC cell
      proliferation, colony formation and G1-S cell-cycle transition, and suppressed
      apoptosis. Molecular mechanistic investigations were performed using an
      integrated approach with a combination of microarray analysis, chromatin
      immunoprecipitation sequencing and a reporter gene assay. The results showed that
      MeCP2 bound to the methylated CpG islands of G-protein-coupled receptor kinase
      interacting protein 1 (GIT1) promoter and upregulated its expression, thereby
      activating the MEK1/2-ERK1/2 signaling pathway and promoting GC cell
      proliferation. Taken together, our study demonstrates that MeCP2, a target of miR
      638, facilitates GC cell proliferation and induces cell-cycle progression through
      activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1. The
      findings suggest that MeCP2 plays a significant role in GC progression, and may
      serve as a potential target for GC therapy.

PMID- 28759024
TI  - MALT1 promotes melanoma progression through JNK/c-Jun signaling.
AB  - Mucosa-associated lymphoma antigen 1 (MALT1) is a lymphoma oncogene that
      regulates signal transduction as a paracaspase and an adaptor protein. Yet, the
      role of MALT1 in other solid cancers such as melanoma is not well-understood.
      Here, we demonstrate that MALT1 is overexpressed in malignant melanoma cells, and
      predicts a poor disease-free survival. MALT1 inhibition via shRNA-mediated gene
      silencing or pharmacologically with MI-2 compound markedly reduced cell growth
      and migration of A2058 and A375 melanoma cell lines in vitro. Subcutaneous tumor
      growth analysis revealed that MALT1 gene silencing significantly reduced tumor
      growth and metastasis to the lung. Consistently, the subcutaneous tumors with
      MALT1 loss had increased cell apoptosis and decreased proliferation. In addition,
      these tumors showed signs of mesenchymal-epithelial transition as indicated by
      the upregulation of E-cadherin and downregulation of N-cadherin and beta1
      intergrin. Further molecular analysis revealed that MALT1 is required for c-Jun
      and nuclear factor-kappaB (NF-kappaB) activation by tumor necrosis factor-alpha.
      Forced expression of the c-Jun upstream activator MKK7 reversed the cell growth
      and migration defects caused by MALT1 loss. In contrast, NF-kappaB activation via
      expression of p65ER, a fusion protein containing NF-kappaB p65 and the tamoxifen
      responsive mutant estrogen receptor, induced minimal effects on cell
      proliferation, but diminished cell death induced by MALT1 loss and TRAIL
      treatment. Together, these findings demonstrate that MALT1 promotes melanoma cell
      proliferation and motility through JNK/c-Jun, and enhances melanoma cell survival
      through NF-kappaB, underscoring MALT1 as a potential therapeutic target and
      biomarker for malignant melanoma.

PMID- 28759026
TI  - Association between GvHD and nivolumab in the FDA adverse event reporting system.

PMID- 28759025
TI  - Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno
      occlusive disease in pediatric patients: a new classification from the European
      society for blood and marrow transplantation.
AB  - The advances in hematopoietic cell transplantation (HCT) over the last decade
      have led to a transplant-related mortality below 15%. Hepatic sinusoidal
      obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening
      complication of HCT that belongs to a group of diseases increasingly identified
      as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD
      resolves within weeks; however, severe SOS/VOD results in multi-organ
      dysfunction/failure with a mortality rate >80%. A timely diagnosis of SOS/VOD is
      of critical importance, given the availability of therapeutic options with
      favorable tolerability. Current diagnostic criteria are used for adults and
      children. However, over the last decade it has become clear that SOS/VOD is
      significantly different between the age groups in terms of incidence, genetic
      predisposition, clinical presentation, prevention, treatment and outcome.
      Improved understanding of SOS/VOD and the availability of effective treatment
      questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in
      children. The aim of this position paper is to propose new diagnostic and
      severity criteria for SOS/VOD in children on behalf of the European Society for
      Blood and Marrow Transplantation.

PMID- 28759027
TI  - Higher rates of relapse in maternal recipients of haploidentical hematopoietic
      stem cell transplantation from adult offspring donors for AML and myelodysplastic
      syndrome.

PMID- 28759028
TI  - Innate immune sensing of cytosolic chromatin fragments through cGAS promotes
      senescence.
AB  - Cellular senescence is triggered by various distinct stresses and characterized
      by a permanent cell cycle arrest. Senescent cells secrete a variety of
      inflammatory factors, collectively referred to as the senescence-associated
      secretory phenotype (SASP). The mechanism(s) underlying the regulation of the
      SASP remains incompletely understood. Here we define a role for innate DNA
      sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP
      synthase (cGAS) recognizes cytosolic chromatin fragments in senescent cells. The
      activation of cGAS, in turn, triggers the production of SASP factors via
      stimulator of interferon genes (STING), thereby promoting paracrine senescence.
      We demonstrate that diverse stimuli of cellular senescence engage the cGAS-STING
      pathway in vitro and we show cGAS-dependent regulation of senescence following
      irradiation and oncogene activation in vivo. Our findings provide insights into
      the mechanisms underlying cellular senescence by establishing the cGAS-STING
      pathway as a crucial regulator of senescence and the SASP.

PMID- 28759029
TI  - Simultaneous epitope and transcriptome measurement in single cells.
AB  - High-throughput single-cell RNA sequencing has transformed our understanding of
      complex cell populations, but it does not provide phenotypic information such as
      cell-surface protein levels. Here, we describe cellular indexing of
      transcriptomes and epitopes by sequencing (CITE-seq), a method in which
      oligonucleotide-labeled antibodies are used to integrate cellular protein and
      transcriptome measurements into an efficient, single-cell readout. CITE-seq is
      compatible with existing single-cell sequencing approaches and scales readily
      with throughput increases.

PMID- 28759030
TI  - Polymer ultrapermeability from the inefficient packing of 2D chains.
AB  - The promise of ultrapermeable polymers, such as poly(trimethylsilylpropyne)
      (PTMSP), for reducing the size and increasing the efficiency of membranes for gas
      separations remains unfulfilled due to their poor selectivity. We report an
      ultrapermeable polymer of intrinsic microporosity (PIM-TMN-Trip) that is
      substantially more selective than PTMSP. From molecular simulations and
      experimental measurement we find that the inefficient packing of the two
      dimensional (2D) chains of PIM-TMN-Trip generates a high concentration of both
      small (<0.7 nm) and large (0.7-1.0 nm) micropores, the former enhancing
      selectivity and the latter permeability. Gas permeability data for PIM-TMN-Trip
      surpass the 2008 Robeson upper bounds for O2/N2, H2/N2, CO2/N2, H2/CH4 and
      CO2/CH4, with the potential for biogas purification and carbon capture
      demonstrated for relevant gas mixtures. Comparisons between PIM-TMN-Trip and
      structurally similar polymers with three-dimensional (3D) contorted chains
      confirm that its additional intrinsic microporosity is generated from the awkward
      packing of its 2D polymer chains in a 3D amorphous solid. This strategy of shape
      directed packing of chains of microporous polymers may be applied to other rigid
      polymers for gas separations.

PMID- 28759031
TI  - Modulation of thermal and thermoelectric transport in individual carbon nanotubes
      by fullerene encapsulation.
AB  - The potential impact of encapsulated molecules on the thermal properties of
      individual carbon nanotubes (CNTs) has been an important open question since the
      first reports of the strong modulation of electrical properties in 2002. However,
      thermal property modulation has not been demonstrated experimentally because of
      the difficulty of realizing CNT-encapsulated molecules as part of thermal
      transport microstructures. Here we develop a nanofabrication strategy that
      enables measurement of the impact of encapsulation on the thermal conductivity
      (kappa) and thermopower (S) of single CNT bundles that encapsulate C 60, Gd@C 82
      and Er 2@C 82. Encapsulation causes 35-55% suppression in kappa and approximately
      40% enhancement in S compared with the properties of hollow CNTs at room
      temperature. Measurements of temperature dependence from 40 to 320 K demonstrate
      a shift of the peak in the kappa to lower temperature. The data are consistent
      with simulations accounting for the interaction between CNTs and encapsulated
      fullerenes.

PMID- 28759032
TI  - Formation of porous crystals via viscoelastic phase separation.
AB  - Viscoelastic phase separation of colloidal suspensions can be interrupted to form
      gels either by glass transition or by crystallization. With a new confocal
      microscopy protocol, we follow the entire kinetics of phase separation, from
      homogeneous phase to different arrested states. For the first time in
      experiments, our results unveil a novel crystallization pathway to sponge-like
      porous crystal structures. In the early stages, we show that nucleation requires
      a structural reorganization of the liquid phase, called stress-driven ageing.
      Once nucleation starts, we observe that crystallization follows three different
      routes: direct crystallization of the liquid phase, the Bergeron process, and
      Ostwald ripening. Nucleation starts inside the reorganized network, but crystals
      grow past it by direct condensation of the gas phase on their surface, driving
      liquid evaporation, and producing a network structure different from the original
      phase separation pattern. We argue that similar crystal-gel states can be formed
      in monatomic and molecular systems if the liquid phase is slow enough to induce
      viscoelastic phase separation, but fast enough to prevent immediate
      vitrification. This provides a novel pathway to form nanoporous crystals of
      metals and semiconductors without dealloying, which may be important for
      catalytic, optical, sensing, and filtration applications.

PMID- 28759033
TI  - One-pot synthesis of silanol-free nanosized MFI zeolite.
AB  - The synthesis of nanostructured zeolites enables modification of catalytically
      relevant properties such as effective surface area and diffusion path length.
      Nanostructured zeolites may be synthesized either in alkaline media, and so
      contain significant numbers of hydrophilic silanol groups, or in expensive and
      harmful fluoride-containing media. Here, we report and characterize, using a
      combination of experimental and theoretical techniques, the one-pot synthesis of
      silanol-free nanosized MFI-type zeolites by introducing atomically dispersed
      tungsten; this prevents silanol group occurrence by forming flexible W-O-Si
      bridges. These W-O-Si bonds are more stable than Si-O-Si in the all-silica MFI
      zeolite. Tungsten incorporation in nanosized MFI crystals also modifies other
      properties such as structural features, hydrophobicity and Lewis acidity. The
      effect of these is illustrated on the catalytic epoxidation of styrene and
      separation of CO2 and NO2. Silanol-free nanosized W-MFI zeolites open new
      perspectives for catalytic and separation applications.

PMID- 28759034
TI  - Microporous polymers: Ultrapermeable membranes.

PMID- 28759035
TI  - SALL4 promotes glycolysis and chromatin remodeling via modulating HP1alpha-Glut1
      pathway.
AB  - SALL4 has recently been identified to promote chemo-resistance in multiple types
      of cancer, but the underlying mechanism remains to be fully established. Open
      chromatin structure is important for DNA damage response (DDR) and DNA repair.
      Here, we demonstrate that SALL4 promotes open chromatin by destabilizing
      heterochromatin protein 1alpha (HP1alpha) by recruiting ubiquitin E3 ligase CUL4B
      to HP1alpha. The silencing of SALL4 in cancer cells decreased the expression
      levels of Glut1 and inhibited glycolysis in cancer cells. The upregulation of
      HP1alpha in human cancer cells suppressed open chromatin, glycolysis and Glut1
      expression levels. Therefore, SALL4 promotes the expression of Glut1 and open
      chromatin through a HP1alpha-dependent mechanism. Impaired DDR in SALL4-deficient
      human cancer cells can be rescued by the restored expression of Glut1, indicating
      the importance of HP1alpha-Glut1 axis in SALL4-mediated DDR. These findings
      demonstrate that SALL4 could induce drug resistance by enhancing DDR and DNA
      repair through promoting glycolysis and subsequent chromatin remodeling.

PMID- 28759036
TI  - Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role
      in regulating cell adhesion and migration.
AB  - Vaccinia H1-related phosphatase (VHR/DUSP3) is a member of the dual-specificity
      phosphatase family. Deregulation of VHR is observed in various malignant
      diseases. We identified focal adhesion kinase (FAK) as a VHR-interacting
      molecule. Over-expression of VHR decreased tyrosine phosphorylation of FAK and
      decreasing VHR promoted FAK tyrosine phosphorylation. In vitro assays proved that
      recombinant VHR directly dephosphorylated FAK and paxillin. VHR-knockout mice did
      not have obvious abnormality; however, VHR-knockout cells showed decreased
      expression of integrins and FAK but stronger FAK and paxillin phosphorylation
      upon attachment to fibronectin. Additionally, VHR-knockout fibroblast and lung
      epithelial cells had elevated ligand-induced epidermal growth factor receptor
      (EGFR) phosphorylation. Inducible expression of VHR suppressed directional cell
      migration, and VHR deficiency resulted in a higher cell migratory ability. VHR
      knockout cells have stronger FAK phosphorylation in cell adhesions, long-lasting
      trailing ends and slower turnover of focal adhesions. These collective data
      indicate that VHR is a FAK phosphatase and participates in regulating the
      formation and disassembly of focal adhesions.

PMID- 28759037
TI  - Role of HSPA1L as a cellular prion protein stabilizer in tumor progression via
      HIF-1alpha/GP78 axis.
AB  - The cellular prion protein (PrPC) is associated with metastasis, tumor
      progression and recurrence; however, the precise mechanisms underlying its action
      is not well understood. Our study found that PrPC degradation decreased tumor
      progression in colorectal cancer (CRC). In a CRC cell line and human CRC tissue
      exposed to hypoxia, induced heat-shock 70-kDa protein-1-like (HSPA1L) expression
      stabilized hypoxia-inducible factor-1alpha (HIF-1alpha) protein and promoted PrPC
      accumulation and tumorigenicity in vivo. PrPC was degraded via the proteasome
      pathway mediated by the ubiquitin-protein E3 ligase glycoprotein 78 (GP78), which
      interacts directly with PrPC. However, hypoxia-induced HSPA1L interacted with
      GP78 and inhibited its functions. HSPA1L knockdown facilitated the interaction of
      GP78 and PrPC, thereby increasing PrPC ubiquitination. Thus, GP78 was identified
      as the ubiquitinase for PrPC, thereby revealing an essential mechanism that
      controls PrPC levels in CRC. Our results suggest that the HSPA1L/HIF-1alpha/GP78
      axis has a crucial role in PrPC accumulation during tumor progression.

PMID- 28759038
TI  - High-depth, high-accuracy microsatellite genotyping enables precision lung cancer
      risk classification.
AB  - There remains a large discrepancy between the known genetic contributions to
      cancer and that which can be explained by genomic variants, both inherited and
      somatic. Recently, understudied repetitive DNA regions called microsatellites
      have been identified as genetic risk markers for a number of diseases including
      various cancers (breast, ovarian and brain). In this study, we demonstrate an
      integrated process for identifying and further evaluating microsatellite-based
      risk markers for lung cancer using data from the cancer genome atlas and the 1000
      genomes project. Comparing whole-exome germline sequencing data from 488 TCGA
      lung cancer samples to germline exome data from 390 control samples from the 1000
      genomes project, we identified 119 potentially informative microsatellite loci.
      These loci were found to be able to distinguish between cancer and control
      samples with sensitivity and specificity ratios over 0.8. Then these loci,
      supplemented with additional loci from other cancers and controls, were evaluated
      using a target enrichment kit and sample-multiplexed nextgen sequencing. Thirteen
      of the 119 risk markers were found to be informative in a well powered study
      (>0.99 for a 0.95 confidence interval) using high-depth (579x+/-315) nextgen
      sequencing of 30 lung cancer and 89 control samples, resulting in sensitivity and
      specificity ratios of 0.90 and 0.94, respectively. When 8 loci harvested from the
      bioinformatic analysis of other cancers are added to the classifier, then the
      sensitivity and specificity rise to 0.93 and 0.97, respectively. Analysis of the
      genes harboring these loci revealed two genes (ARID1B and REL) and two
      significantly enriched pathways (chromatin organization and cellular stress
      response) suggesting that the process of lung carcinogenesis is linked to
      chromatin remodeling, inflammation, and tumor microenvironment restructuring. We
      illustrate that high-depth sequencing enables a high-precision microsatellite
      based risk classifier analysis approach. This microsatellite-based platform
      confirms the potential to create clinically actionable diagnostics for lung
      cancer.

PMID- 28759039
TI  - Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer
      growth in mouse models of hyperlipidemia.
AB  - Obesity is associated with an increase in cancer-specific mortality in women with
      breast cancer. Elevated cholesterol, particularly low-density lipoprotein
      cholesterol (LDL-C), is frequently seen in obese women. Here, we aimed to
      determine the importance of elevated circulating LDL, and LDL receptor (LDLR)
      expression in tumor cells, on the growth of breast cancer using mouse models of
      hyperlipidemia. We describe two novel immunodeficient mouse models of
      hyperlipidemia (Rag1-/-/LDLR-/- and Rag1-/-/ApoE (apolipoprotein E)-/- mice) in
      addition to established immunocompetent LDLR-/- and ApoE-/- mice. The mice were
      used to study the effects of elevated LDL-C in human triple-negative (MDA-MB-231)
      and mouse Her2/Neu-overexpressing (MCNeuA) breast cancers. Tumors derived from
      MCNeuA and MDA-MB-231 cells had high LDLR expression and formed larger tumors in
      mice with high circulating LDL-C concentrations than in mice with lower LDL-C.
      Silencing the LDLR in the tumor cells led to decreased growth of Her2/Neu
      overexpressing tumors in LDLR-/- and ApoE-/- mice, with increased Caspase 3
      cleavage. Additionally, in vitro, silencing the LDLR led to decreased cell
      survival in serum-starved conditions, associated with Caspase 3 cleavage.
      Examining publically available human data sets, we found that high LDLR
      expression in human breast cancers was associated with decreased recurrence-free
      survival, particularly in patients treated with systemic therapies. Overall, our
      results highlight the importance of the LDLR in the growth of triple-negative and
      HER2-overexpressing breast cancers in the setting of elevated circulating LDL-C,
      which may be important contributing factors to the increased recurrence and
      mortality in obese women with breast cancer.

PMID- 28759040
TI  - TEAD1/4 exerts oncogenic role and is negatively regulated by miR-4269 in gastric
      tumorigenesis.
AB  - TEA domain (TEAD) transcription factors are key components of the Hippo-YAP1
      signaling pathway, but their functional role and regulatory mechanisms remain
      unclear. This study aims to comprehensively explore the expression pattern and
      functional role of TEAD family in gastric carcinogenesis and investigate its
      regulation by microRNAs (miRNAs). The mRNA and protein expression of TEAD family
      were examined by quantitative reverse transcription-PCR (qRT-PCR) and western
      blot. Their functional roles were determined by in vitro and in vivo studies. The
      clinicopathological association of TEAD4 in gastric cancer (GC) was studied using
      immunohistochemistry on tissue microarray. The prediction of miRNAs, which
      potentially target TEAD1/4, was performed by TargetScan and miRDB. The regulation
      of TEAD1/4 by miRNAs was confirmed by qRT-PCR, western blot and luciferase
      assays. TEAD1/4 were overexpressed in GC cell lines and primary GC tissues.
      Knockdown of TEAD1/4 induced a significant anticancer effect in vitro and in
      vivo. TEAD1 was confirmed to be a direct target of miR-377-3p and miR-4269, while
      TEAD4 was negatively regulated by miR-1343-3p and miR-4269. Among them, miR-4269
      was the most effective inhibitor of TEAD1/4. Ectopic expression of these miRNAs
      substantiated their tumor-suppressive effects. In primary GC tumors,
      downregulation of miR-4269 was associated with poor disease-specific survival and
      showed a negative correlation with TEAD4. TEAD1 and TEAD4 are oncogenic factors,
      whose aberrant activation are, in part, mediated by the silence of miR-377-3p,
      miR-1343-3p and miR-4269. For the first time, the nuclear accumulated TEAD4 and
      downregulated miR-4269 are proposed to serve as novel prognostic biomarkers in
      GC.

PMID- 28759041
TI  - Oncosis and apoptosis induction by activation of an overexpressed ion channel in
      breast cancer cells.
AB  - The critical role of calcium signalling in processes related to cancer cell
      proliferation and invasion has seen a focus on pharmacological inhibition of
      overexpressed ion channels in specific cancer subtypes as a potential therapeutic
      approach. However, despite the critical role of calcium in cell death pathways,
      pharmacological activation of overexpressed ion channels has not been extensively
      evaluated in breast cancer. Here we define the overexpression of transient
      receptor potential vanilloid 4 (TRPV4) in a subgroup of breast cancers of the
      basal molecular subtype. We also report that pharmacological activation of TRPV4
      with GSK1016790A reduced viability of two basal breast cancer cell lines with
      pronounced endogenous overexpression of TRPV4, MDA-MB-468 and HCC1569.
      Pharmacological activation of TRPV4 produced pronounced cell death through two
      mechanisms: apoptosis and oncosis in MDA-MB-468 cells. Apoptosis was associated
      with PARP-1 cleavage and oncosis was associated with a rapid decline in
      intracellular ATP levels, which was a consequence of, rather than the cause of,
      the intracellular ion increase. TRPV4 activation also resulted in reduced tumour
      growth in vivo. These studies define a novel therapeutic strategy for breast
      cancers that overexpress specific calcium permeable plasmalemmal ion channels
      with available selective pharmacological activators.

PMID- 28759042
TI  - Inhibition of the spindle assembly checkpoint kinase Mps-1 as a novel therapeutic
      strategy in malignant mesothelioma.
AB  - Malignant mesothelioma (MM) is an aggressive malignancy, highly resistant to
      current medical and surgical therapies, whose tumor cells characteristically show
      a high level of aneuploidy and genomic instability. We tested our hypothesis that
      targeting chromosomal instability in MM would improve response to therapy.
      Thr/Tyr kinase (TTK)/monopolar spindle 1 kinase (Mps-1) is a kinase of the
      spindle assembly checkpoint that controls cell division and cell fate. CFI-402257
      is a novel, selective inhibitor of Mps-1 with antineoplastic activity. We found
      that CFI-402257 suppresses MM growth. We found that Mps-1 is overexpressed in MM
      and that its expression correlates with poor patients' outcome. In vitro, CFI
      402257-mediated inhibition of Mps-1 resulted in abrogation of the mitotic
      checkpoint, premature progression through mitosis, marked aneuploidy and mitotic
      catastrophe. In vivo, CFI-402257 reduced MM growth in an orthotopic, syngeneic
      model, when used as a single agent, and more so when used in combination with
      cisplatin+pemetrexed, the current standard of care. Our preclinical findings
      indicate that CFI-402257 is a promising novel therapeutic agent to improve the
      efficacy of the current chemotherapeutic regimens for MM patients.

PMID- 28759044
TI  - Inhibition of colony stimulating factor-1 receptor abrogates microenvironment
      mediated therapeutic resistance in gliomas.
AB  - Glioblastomas represent the most aggressive glioma grade and are associated with
      a poor patient prognosis. The current standard of care, consisting of surgery,
      radiation and chemotherapy, only results in a median survival of 14 months,
      underscoring the importance of developing effective new therapeutic strategies.
      Among the challenges in treating glioblastomas are primary resistance and the
      rapid emergence of recurrent disease, which can result from tumor cell-intrinsic
      mechanisms in addition to tumor microenvironment (TME)-mediated extrinsic
      resistance. Using a PDGF-B-driven proneural glioma mouse model, we assessed a
      panel of tyrosine kinase inhibitors with different selectivity profiles. We found
      that PLX3397, an inhibitor of colony stimulating factor-1 receptor (CSF-1R),
      blocks glioma progression, markedly suppresses tumor cell proliferation and
      reduces tumor grade. By contrast, the multi-targeted tyrosine kinase inhibitors
      dovitinib and vatalanib, which directly target tumor cells, exert minimal anti
      tumoral effects in vivo, despite killing glioma cells in vitro, suggesting a TME
      mediated resistance mechanism may be involved. Interestingly, PLX3397 interferes
      with tumor-mediated education of macrophages and consequently restores the
      sensitivity of glioma cells to tyrosine kinase inhibitors in vivo in preclinical
      combination trials. Our findings thus demonstrate that microenvironmental
      alteration by CSF-1R blockade renders tumor cells more susceptible to receptor
      tyrosine kinase inhibition in a preclinical glioblastoma model, which may have
      important translational relevance.

PMID- 28759043
TI  - Genome-wide screen for differentially methylated long noncoding RNAs identifies
      Esrp2 and lncRNA Esrp2-as regulated by enhancer DNA methylation with prognostic
      relevance for human breast cancer.
AB  - The majority of long noncoding RNAs (lncRNAs) is still poorly characterized with
      respect to function, interactions with protein-coding genes, and mechanisms that
      regulate their expression. As for protein-coding RNAs, epigenetic deregulation of
      lncRNA expression by alterations in DNA methylation might contribute to
      carcinogenesis. To provide genome-wide information on lncRNAs aberrantly
      methylated in breast cancer we profiled tumors of the C3(1) SV40TAg mouse model
      by MCIp-seq (Methylated CpG Immunoprecipitation followed by sequencing). This
      approach detected 69 lncRNAs differentially methylated between tumor tissue and
      normal mammary glands, with 26 located in antisense orientation of a protein
      coding gene. One of the hypomethylated lncRNAs, 1810019D21Rik (now called Esrp2
      antisense (as)) was identified in proximity to the epithelial splicing regulatory
      protein 2 (Esrp2) that is significantly elevated in C3(1) tumors. ESRPs were
      shown previously to have a dual role in carcinogenesis. Both gain and loss have
      been associated with poor prognosis in human cancers, but the mechanisms
      regulating expression are not known. In-depth analyses indicate that coordinate
      overexpression of Esrp2 and Esrp2-as inversely correlates with DNA methylation.
      Luciferase reporter gene assays support co-expression of Esrp2 and the major
      short Esrp2-as variant from a bidirectional promoter, and transcriptional
      regulation by methylation of a proximal enhancer. Ultimately, this enhancer-based
      regulatory mechanism provides a novel explanation for tissue-specific expression
      differences and upregulation of Esrp2 during carcinogenesis. Knockdown of Esrp2
      as reduced Esrp2 protein levels without affecting mRNA expression and resulted in
      an altered transcriptional profile associated with extracellular matrix (ECM),
      cell motility and reduced proliferation, whereas overexpression enhanced
      proliferation. Our findings not only hold true for the murine tumor model, but
      led to the identification of an unannotated human homolog of Esrp2-as which is
      significantly upregulated in human breast cancer and associated with poor
      prognosis.

PMID- 28759045
TI  - Tumor microenvironment confers mTOR inhibitor resistance in invasive intestinal
      adenocarcinoma.
AB  - Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is frequently activated
      in cancers and can be counteracted with the clinical mTORC1 inhibitors everolimus
      and temsirolimus. Although mTORC1 and dual mTORC1/2 inhibitors are currently
      under development to treat various malignancies, the emergence of drug resistance
      has proven to be a major complication. Using the cis-Apc/Smad4 mouse model of
      locally invasive intestinal adenocarcinoma, we show that administration of
      everolimus or the dual mTORC1/2 inhibitor AZD8055 significantly reduces the
      growth of intestinal tumors. In contrast, although everolimus treatment at
      earlier phase of tumor progression delayed invasion of the tumors, both
      inhibitors exhibited little effect on blocking invasion of the tumors when
      administered later in their progression. Biochemical and immunohistochemical
      analyses revealed that treatment of cis-Apc/Smad4 mice with everolimus or AZD8055
      induced marked increases in epidermal growth factor receptor (EGFR) and MEK/ERK
      signaling in tumor epithelial and stromal cells, respectively. Notably, co
      administration of AZD8055 and the EGFR inhibitor erlotinib or the MEK inhibitor
      trametinib was sufficient to suppress tumor invasion in cis-Apc/Smad4 mice. These
      data indicate that mTOR inhibitor resistance in invasive intestinal tumors
      involves feedback signaling from both cancer epithelial and stromal cells,
      highlighting the role of tumor microenvironment in drug resistance, and support
      that simultaneous inhibition of mTOR and EGFR or MEK may be more effective in
      treating colon cancer.

PMID- 28759047
TI  - Correction: Stop neglecting fungi.
AB  - This corrects the article DOI: 10.1038/nmicrobiol.2017.120.

PMID- 28759046
TI  - EZH2-mediated upregulation of ROS1 oncogene promotes oral cancer metastasis.
AB  - Current anti-epidermal growth factor receptor (EGFR) therapy for oral cancer does
      not provide satisfactory efficacy due to drug resistance or reduced EGFR level.
      As an alternative candidate target for therapy, here we identified an oncogene,
      ROS1, as an important driver for oral squamous cell carcinoma (OSCC) metastasis.
      Among tumors from 188 oral cancer patients, upregulated ROS1 expression strongly
      correlated with metastasis to lung and lymph nodes. Mechanistic studies uncover
      that the activated ROS1 results from highly expressed ROS1 gene instead of gene
      rearrangement, a phenomenon distinct from other cancers. Our data further reveal
      a novel mechanism that reduced histone methyltransferase EZH2 leads to a lower
      trimethylation of histone H3 lysine 27 suppressive modification, relaxes
      chromatin, and promotes the accessibility of the transcription factor STAT1 to
      the enhancer and the intron regions of ROS1 target genes, CXCL1 and GLI1, for
      upregulating their expressions. Down-regulation of ROS1 in highly invasive OSCC
      cells, nevertheless, reduces cell proliferation and inhibits metastasis to lung
      in the tail-vein injection and the oral cavity xenograft models. Our findings
      highlight ROS1 as a candidate biomarker and therapeutic target for OSCC. Finally,
      we demonstrate that co-targeting of ROS1 and EGFR could potentially offer an
      effective oral cancer therapy.

PMID- 28759048
TI  - Decoding the selectivity of eIF2alpha holophosphatases and PPP1R15A inhibitors.
AB  - The reversible phosphorylation of proteins controls most cellular functions.
      Protein kinases have been popular drug targets, unlike phosphatases, which remain
      a drug discovery challenge. Guanabenz and Sephin1 are selective inhibitors of the
      phosphatase regulatory subunit PPP1R15A (R15A) that prolong the benefit of
      eIF2alpha phosphorylation, thereby protecting cells from proteostatic defects. In
      mice, Sephin1 prevents two neurodegenerative diseases, Charcot-Marie-Tooth 1B
      (CMT-1B) and SOD1-mediated amyotrophic lateral sclerosis (ALS). However, the
      molecular basis for R15A inhibition is unknown. Here we reconstituted human
      recombinant eIF2alpha holophosphatases, R15A-PP1 and R15B-PP1, whose activity
      depends on both the catalytic subunit PP1 (protein phosphatase 1) and either R15A
      or R15B. This system enabled the functional characterization of these
      holophosphatases and revealed that Guanabenz and Sephin1 induced a selective
      conformational change in R15A, detected by resistance to limited proteolysis.
      This altered the recruitment of eIF2alpha, preventing its dephosphorylation. This
      work demonstrates that regulatory subunits of phosphatases are valid drug targets
      and provides the molecular rationale to expand this concept to other
      phosphatases.

PMID- 28759049
TI  - Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent
      TLR4 signaling.
AB  - Toll-like receptor (TLR) signaling is a key innate immunity response to
      pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the
      TLRs requires Toll/interleukin-1 receptor (TIR)-domain interactions, which remain
      structurally elusive. Here we show that MAL TIR domains spontaneously and
      reversibly form filaments in vitro. They also form cofilaments with TLR4 TIR
      domains and induce formation of MyD88 assemblies. A 7-A-resolution cryo-EM
      structure reveals a stable MAL protofilament consisting of two parallel strands
      of TIR-domain subunits in a BB-loop-mediated head-to-tail arrangement. Interface
      residues that are important for the interaction are conserved among different TIR
      domains. Although large filaments of TLR4, MAL or MyD88 are unlikely to form
      during cellular signaling, structure-guided mutagenesis, combined with in vivo
      interaction assays, demonstrated that the MAL interactions defined within the
      filament represent a template for a conserved mode of TIR-domain interaction
      involved in both TLR and interleukin-1 receptor signaling.

PMID- 28759050
TI  - Rps26 directs mRNA-specific translation by recognition of Kozak sequence
      elements.
AB  - We describe a novel approach to separate two ribosome populations from the same
      cells and use this method in combination with RNA-seq to identify mRNAs bound to
      Saccharomyces cerevisiae ribosomes with and without Rps26, a protein linked to
      the pathogenesis of Diamond-Blackfan anemia (DBA). These analyses reveal that
      Rps26 contributes to mRNA-specific translation by recognition of the Kozak
      sequence in well-translated mRNAs and that Rps26-deficient ribosomes
      preferentially translate mRNA from select stress-response pathways. Surprisingly,
      exposure of yeast to these stresses leads to the formation of Rps26-deficient
      ribosomes and to the increased translation of their target mRNAs. These results
      describe a novel paradigm: the production of specialized ribosomes, which play
      physiological roles in augmenting the well-characterized transcriptional stress
      response with a heretofore unknown translational response, thereby creating a
      feed-forward loop in gene expression. Moreover, the simultaneous gain-of-function
      and loss-of-function phenotypes from Rps26-deficient ribosomes can explain the
      pathogenesis of DBA.

PMID- 28759051
TI  - Implications of human genetic variation in CRISPR-based therapeutic genome
      editing.
AB  - CRISPR-Cas genome-editing methods hold immense potential as therapeutic tools to
      fix disease-causing mutations at the level of DNA. In contrast to typical drug
      development strategies aimed at targets that are highly conserved among
      individual patients, treatment at the genomic level must contend with substantial
      inter-individual natural genetic variation. Here we analyze the recently released
      ExAC and 1000 Genomes data sets to determine how human genetic variation impacts
      target choice for Cas endonucleases in the context of therapeutic genome editing.
      We find that this genetic variation confounds the target sites of certain Cas
      endonucleases more than others, and we provide a compendium of guide RNAs
      predicted to have high efficacy in diverse patient populations. For further
      analysis, we focus on 12 therapeutically relevant genes and consider how genetic
      variation affects off-target candidates for these loci. Our analysis suggests
      that, in large populations of individuals, most candidate off-target sites will
      be rare, underscoring the need for prescreening of patients through whole-genome
      sequencing to ensure safety. This information can be integrated with empirical
      methods for guide RNA selection into a framework for designing CRISPR-based
      therapeutics that maximizes efficacy and safety across patient populations.

PMID- 28759052
TI  - D-mannose induces regulatory T cells and suppresses immunopathology.
AB  - D-mannose, a C-2 epimer of glucose, exists naturally in many plants and fruits,
      and is found in human blood at concentrations less than one-fiftieth of that of
      glucose. However, although the roles of glucose in T cell metabolism, diabetes
      and obesity are well characterized, the function of D-mannose in T cell immune
      responses remains unknown. Here we show that supraphysiological levels of D
      mannose safely achievable by drinking-water supplementation suppressed
      immunopathology in mouse models of autoimmune diabetes and airway inflammation,
      and increased the proportion of Foxp3+ regulatory T cells (Treg cells) in mice.
      In vitro, D-mannose stimulated Treg cell differentiation in human and mouse cells
      by promoting TGF-beta activation, which in turn was mediated by upregulation of
      integrin alphavbeta8 and reactive oxygen species generated by increased fatty
      acid oxidation. This previously unrecognized immunoregulatory function of D
      mannose may have clinical applications for immunopathology.

PMID- 28759053
TI  - The eukaryotic gut virome in hematopoietic stem cell transplantation: new clues
      in enteric graft-versus-host disease.
AB  - Much attention has been focused on the role of the bacterial microbiome in human
      health, but the virome is understudied. Although previously investigated in
      individuals with inflammatory bowel diseases or solid-organ transplants, virome
      dynamics in allogeneic hematopoietic stem cell transplantation (HSCT) and enteric
      graft-versus-host disease (GVHD) remain unexplored. Here we characterize the
      longitudinal gut virome in 44 recipients of HSCT using metagenomics. A viral
      'bloom' was identified, and significant increases were demonstrated in the
      overall proportion of vertebrate viral sequences following transplantation (P =
      0.02). Increases in both the rates of detection (P < 0.0001) and number of
      sequences (P = 0.047) of persistent DNA viruses (anelloviruses, herpesviruses,
      papillomaviruses and polyomaviruses) over time were observed in individuals with
      enteric GVHD relative to those without, a finding accompanied by a reduced phage
      richness (P = 0.01). Picobirnaviruses were detected in 18 individuals (40.9%),
      more frequently before or within a week after transplant than at later time
      points (P = 0.008). In a time-dependent Cox proportional-hazards model,
      picobirnaviruses were predictive of the occurrence of severe enteric GVHD (hazard
      ratio, 2.66; 95% confidence interval (CI) = 1.46-4.86; P = 0.001), and correlated
      with higher fecal levels of two GVHD severity markers, calprotectin and alpha1
      antitrypsin. These results reveal a progressive expansion of vertebrate viral
      infections over time following HSCT, and they suggest an unexpected association
      of picobirnaviruses with early post-transplant GVHD.

PMID- 28759054
TI  - The association between retinal vein pulsation pressure and optic disc
      haemorrhages in glaucoma.
AB  - PURPOSE: To explore the potential relationship between optic disc haemorrhage,
      venous pulsation pressure (VPP), ocular perfusion pressures and visual field
      change in glaucomatous and glaucoma suspect eyes. MATERIALS AND METHODS: This
      prospective observational study examined 155 open angle glaucoma or glaucoma
      suspect eyes from 78 patients over 5 years. Patients were followed with 3 monthly
      non-mydriatic disc photographs, 6 monthly standard automated perimetry and annual
      ophthalmodynamometry. The number of disc haemorrhages in each hemidisc was
      counted across the study period. Visual field rate of change was calculated using
      linear regression on the sensitivity of each location over time, then averaged
      for the matching hemifield. VPP and central retinal artery diastolic pressure
      (CRADP) were calculated from the measured ophthalmodynanometric forces (ODF). The
      difference between brachial artery diastolic pressure (DiastBP) and CRADP was
      calculated as an index of possible flow pathology along the carotid and
      ophthalmic arteries. RESULTS: Mean age of the cohort was 71.9 +/- 7.3 Years. 76
      out of 155 eyes (49%) followed for a mean period of 64.2 months had at least 1
      disc haemorrhage. 62 (81.6%) of these 76 eyes had recurrent haemorrhages, with a
      mean of 5.94 recurrences over 64.2 months. Using univariate analysis, rate of
      visual field change (P<0.0001), VPP (P = 0.0069), alternative ocular perfusion
      pressure (CRADP-VPP, P = 0.0036), carotid resistance index (DiastBP-CRADP, P =
      0.0108) and mean brachial blood pressure (P = 0.0203) were significantly
      associated with the number of disc haemorrhages. Using multivariate analysis,
      increased baseline visual field sensitivity (P = 0.0243, coefficient = 0.0275)
      was significantly associated with disc haemorrhage, in conjunction with higher
      VPP (P = 0.0029, coefficient = 0.0631), higher mean blood pressure (P = 0.0113,
      coefficient = 0.0190), higher carotid resistance index (P = 0.0172, coefficient =
      0.0566), and rate of visual field loss (P<0.0001, coefficient = -2.0695).
      CONCLUSIONS: Higher VPP was associated with disc haemorrhage and implicates the
      involvement of venous pathology, but the effect size is small. Additionally, a
      greater carotid resistance index suggests that flow pathology in the ophthalmic
      or carotid arteries may be associated with disc haemorrhage.

PMID- 28759055
TI  - A role for the tfs3 ICE-encoded type IV secretion system in pro-inflammatory
      signalling by the Helicobacter pylori Ser/Thr kinase, CtkA.
AB  - Two distinct type IV secretion systems (T4SSs) can be identified in certain
      Helicobacter pylori strains, encoded on mobile genetic elements termed tfs3 and
      tfs4. Although their function remains unknown, both have been implicated in
      clinical outcomes of H. pylori infection. Here we provide evidence that the Tfs3
      T4SS is required for activity of the pro-inflammatory Ser/Thr kinase protein,
      CtkA, in a gastric epithelial cell infection model. Previously, purified
      recombinant CtkA protein has been shown to upregulate NF-kappaB signalling and
      induce TNF-alpha and IL-8 cytokine secretion from cultured macrophages suggesting
      that it may potentiate the H. pylori-mediated inflammatory response. In this
      study, we show that CtkA expressed from its native host, H. pylori has a similar
      capacity for stimulation of a pro-inflammatory response from gastric epithelial
      cells. CtkA interaction was found to be dependent upon a complement of tfs3 T4SS
      genes, but independent of the T4SSs encoded by either tfs4 or the cag
      pathogenicity island. Moreover, the availability of CtkA for host cell
      interaction was shown to be conditional upon the carboxyl-terminus of CtkA,
      encoding a putative conserved secretion signal common to other variably encoded
      Tfs3 proteins. Collectively, our observations indicate a role for the Tfs3 T4SS
      in CtkA-mediated pro-inflammatory signalling by H. pylori and identify CtkA as a
      likely Tfs3 T4SS secretion substrate.

PMID- 28759056
TI  - Redox-responsive xanthene-coumarin-chlorambucil-based FRET-guided theranostics
      for "activatable" combination therapy with real-time monitoring.
AB  - A FRET donor-acceptor xanthene-coumarin conjugate has been designed for redox
      regulated synergic treatment of photodynamic therapy and chemotherapy with real
      time monitoring. The "locked" FRET pair was selectively "unlocked" by biological
      reducing thiols via rupture of a sacrificial disulfide linker. A distinct change
      in fluorescence color and selective cancer cell toxicity were observed in vitro.

PMID- 28759057
TI  - Recent trends in electrochemiluminescence aptasensors and their applications.
AB  - Aptamers are single stranded DNA or RNA ligands which can be selected for
      different targets from proteins to small organic dyes. In the past few years
      great progress has been accomplished in the development of aptamer based
      bioanalytical assays with different detection techniques. Among them,
      electrochemiluminescence (ECL) aptasensors are very promising because they have
      the advantages of both electrochemical and chemiluminescence biosensors, such as
      high sensitivity, low background, cost effectiveness, and ease of control. In
      this review, we summarize the recent efforts to construct novel and improved ECL
      aptasensors and their application.

PMID- 28759058
TI  - Nanoporous polysulfones with in situ PEGylated surfaces by a simple swelling
      strategy using paired solvents.
AB  - We report the formation of three-dimensionally interconnected nanoporosities with
      in situ PEGylated pore walls simply by swelling the block copolymers of
      polysulfone and poly(ethylene glycol) in paired solvents. The produced nanoporous
      polymers are expected to find important applications in membranes, batteries,
      chromatography, and haemodialysis.

PMID- 28759059
TI  - Impact of an ionic liquid on protein thermodynamics in the presence of cold
      atmospheric plasma and gamma rays.
AB  - Cold atmospheric plasma and gamma rays are known to have anticancer properties,
      even though their specific mechanisms and roles as co-solvents during their
      action are still not clearly understood. Despite the use of gamma rays in cancer
      therapy, they have oncogenic potential, whereas this has not been observed for
      plasma treatment (to date). To gain a better understanding, we studied the action
      of dielectric barrier discharge (DBD) plasma and gamma rays on the myoglobin
      protein. We analyzed the secondary structure and thermodynamic properties of
      myoglobin after both treatments. In addition, in the last few years, ammonium
      ionic liquids (ILs) have revealed their important role in protein folding as co
      solvents. In this work, we treated the protein with ammonium ILs such as
      triethylammonium methanesulfonate (TEMS) and tetrabutylammonium methanesulfonate
      (TBMS) and later treated this IL-protein solution with DBD plasma and gamma rays.
      In this study, we show the chemical and thermal denaturation of the protein after
      plasma and gamma treatments in the presence and absence of ILs using circular
      dichroism (CD) and UV-vis spectroscopy. Furthermore, we also show the influence
      of plasma and gamma rays on the secondary structure of myoglobin in the absence
      and presence of ILs or ILs + urea using CD. Finally, molecular dynamic
      simulations were conducted to gain deeper insight into how the ILs behave to
      protect the protein against the hydrogen peroxide generated by the DBD plasma and
      gamma rays.

PMID- 28759060
TI  - Mechanical response of collagen networks to nonuniform microscale loads.
AB  - As force is applied to fibrous proteins such as collagen or fibrin, the fibers
      respond by bending, stretching, or buckling, which together bring about a
      nonlinear relationship between force and displacement. The nonlinearity is
      typically understood in terms of strain stiffening in uniform extension or shear,
      but there remains a critical lack of data on how fibrous materials respond to
      other more complicated loadings. Here we study the mechanics of collagen networks
      in response to nonuniform loads applied on the local scale of the fibers. For
      this, we use particles made of an active hydrogel that undergoes a temperature
      induced phase transition causing a large decrease in volume. We embed these
      particles in networks of fibrous collagen and use them as microactuators to apply
      controlled microscale loading. The resulting fiber displacements propagate over a
      long range with radial displacements u scaling as r-n with n ~ 1. By contrast, we
      find linear homogeneous materials have n ~ 2, in agreement with classical linear
      elastic theory. Our experimental data supports the notion that the long range
      displacements result from buckling of fibers in compression and local
      straightening of fibers in tension, in agreement with previous studies.
      Surprisingly, global network anisotropy appears to have only a modest effect on
      the displacement propagation. These insights into the microscale mechanics
      demonstrate that the decay power n provides a useful metric to quantify the
      mechanics of fibrous materials. We therefore suggest it is a means to compare new
      theories with experimental data.

PMID- 28759061
TI  - Molecular rotors confined at an ordered 2D interface.
AB  - Intramolecular rotation of molecules contained in a two-dimensional monolayer or
      a three-dimensional collapsed film at an air-water interface was investigated by
      in situ fluorescence spectroscopy of twisted intramolecular charge transfer
      (TICT) type 9-(2-carboxy-2-cyanovinyl)julolidine (CCVJ) derivatives. The TICT
      type molecules, CCVJ-C12 and CCVJ-Chol, that contain a linear alkyl dodecyl chain
      or a cholesteryl group, respectively, as their hydrophobic group, were designed
      and synthesized to manipulate them at the air-water interface. These lipophilized
      molecular rotors showed the general properties of TICT molecules in solutions
      that the fluorescence intensity increases with increasing viscosity of the
      solvent, which is induced by inhibition of internal molecular rotations. The
      molecular rotors CCVJ-C12 and CCVJ-Chol formed monolayers at the air-water
      interface and in situ fluorescence spectroscopy was performed during the in-plane
      compression of the monolayers. It was revealed that the monomer emissions were
      suppressed and only after the collapse of monolayers, excimer emission from both
      layers consisting of CCVJ-C12 or CCVJ-Chol was observed. Suppressed monomer
      emission from monolayers suggests that intramolecular rotation is not inhibited
      in dense ordered monolayers. Furthermore, fluorescence spectroscopy of Langmuir
      Blodgett (LB) films indicated that molecular rotations are not inhibited in the
      monolayer transferred on the solid substrates.

PMID- 28759062
TI  - Copper-finger protein of Sp1: the molecular basis of copper sensing.
AB  - The cellular copper level is strictly regulated since excessive copper is harmful
      to cells. It has been proposed that the expression of copper transport protein
      hCtr1 is transcriptionally regulated by specificity protein 1 (Sp1) in response
      to the cellular copper level. However, it is not known how Sp1, a zinc-finger
      protein (ZFP), can sense copper ions in cells. Here we found that Sp1
      demonstrates high binding affinity to cuprous ions, even stronger than Cu-Atox1
      binding. Cu(i) can displace Zn(ii) in Sp1, resulting in a well-folded 'Copper
      Finger-Protein' (CFP). Although only very little structural alteration occurs
      upon copper binding, CFP cannot recognize the promoter of hCtr1, therefore copper
      binding interrupts the transcription. This result indicates that, in addition to
      apo-to-holo alteration, metal substitution can also lead to transcriptional
      switch in metal sensing. This work provides insight into the copper sensing
      mechanism of Sp1 at the molecular level.

PMID- 28759063
TI  - Phase and morphological control of MoO3-x nanostructures for efficient cancer
      theragnosis therapy.
AB  - Nanostructures of metal oxide semiconductors play significant roles in a variety
      of areas, such as biotherapy, pollutant treatment and energy storage and
      conversion. The molybdenum oxide (MoO3-x) nanostructures have shown promising
      applications especially when used as photothermal treatment agents due to their
      relatively low cost, facile synthesis and low toxicity. However, the design and
      synthesis of efficient MoO3-x nanomaterials with tunable phases and morphologies
      for theragnosis of tumors remains a challenge. In this work, hydrophilic MoO3-x
      with controlled structures and phases was synthesized by a simple one-step
      hydrothermal process. The as-obtained MoO2 nanoclusters showed a desirable size
      of ~40 nm in diameter exhibiting unique properties as a theragnosis nanoplatform:
      (1) strong near-infrared absorption, which is due to oxygen vacancies of the
      nanoclusters, as proved by photoluminescence spectroscopy and X-ray photoelectron
      spectroscopy; (2) excellent photothermal performance with a photothermal
      conversion efficiency of up to 62.1%; and (3) the image response of X-ray
      computed tomography (CT) and infrared thermal imaging for simultaneous diagnosis
      of tumors. This study provided the facile synthetic strategy for controllable
      metal oxide semiconductors and promoted the development of metal oxides for
      theragnosis therapy of cancers.

PMID- 28759064
TI  - Precise preparation of layered Na0.5Ni0.25Mn0.75O2 micro-sheets for 3.8 V Na-ion
      batteries.
AB  - Novel layered Na0.5Ni0.25Mn0.75O2 micro-sheets were explored as cathode materials
      for Na-ion batteries for the first time, which can exhibit electrochemical
      activity operating at an average voltage of 3.8 V (vs. Na+/Na) and deliver a
      reversible discharge capacity of 121 mA h g-1 at 0.2C rate.

PMID- 28759065
TI  - Importance of non-intrinsic platinum dissolution in Pt/C composite fuel cell
      catalysts.
AB  - The dissolution of different platinum-based nanoparticles deposited on a
      commercial high-surface area carbon (HSAC) support in thin catalyst films is
      investigated using a highly sensitive electrochemical flow cell (EFC) coupled to
      an inductively coupled plasma mass spectrometer (ICP-MS). The previously reported
      particle-size-dependent dissolution of Pt is confirmed on selected industrial
      samples with a mean Pt particle size ranging from 1 to 4.8 nm. This trend is
      significantly altered when a catalyst is diluted by the addition of HSAC. This
      indicates that the intrinsic dissolution properties are masked by local
      oversaturation phenomena, the so-called confinement effect. Furthermore, by
      replacing the standard HSAC support with a support having an order of magnitude
      higher specific surface area (a micro- and mesoporous nitrogen-doped high surface
      area carbon, HSANDC), Pt dissolution is reduced even further. This is due to the
      so-called non-intrinsic confinement and entrapment effects of the (large amount
      of) micropores and small mesopores doped with N atoms. The observed more
      effective Pt re-deposition is presumably induced by local Pt oversaturation and
      the presence of nitrogen nucleation sites. Overall, our study demonstrates the
      high importance and beneficial effects of porosity, loading and N doping of the
      carbon support on the Pt stability in the catalyst layer.

PMID- 28759067
TI  - Indirect NMR detection of transient guanosyl radical protonation in neutral
      aqueous solution.
AB  - By using the time-resolved chemically induced dynamic nuclear polarization
      technique, we show that the neutral guanosyl radical, G(-H), formed in the
      reaction of guanosine-5'-monophosphate with a triplet-excited 3,3',4,4'
      tetracarboxy benzophenone in neutral aqueous solution, protonates readily at the
      N7 position with the formation of a new guanosyl cation radical (G+)'.

PMID- 28759066
TI  - Structural changes and picosecond to second dynamics of cytochrome c in
      interaction with nitric oxide in ferrous and ferric redox states.
AB  - Apart from its role in electron transfer, mitochondrial cytochrome c also plays a
      role in apoptosis and is subject to nitrosylation. The cleavage of the Fe-Met80
      bond plays a role in several processes including the release of Cyt c from
      mitochondria or increase of its peroxidase activity. Nitrosylation of Cyt c
      precludes the reformation of the disrupted Fe-Met80 bond and was shown to occur
      during apoptosis. These physiological properties are associated with a
      conformational change of the heme center of Cyt c. Here, we demonstrate that NO
      binding induces pronounced heme conformational changes in the six-coordinate Cyt
      c-NO complex. Equilibrium and time-resolved Raman data reveal that the heme
      structural conformation depends both on the nature of the distal iron ligand (NO
      or Met80) and on the Fe2+ or Fe3+ heme redox state. Upon nitrosylation, the heme
      ruffling distortion is greatly enhanced for ferrous Cyt c. Contrastingly, the
      initial strong heme distortion in native ferric Cyt c almost disappears after NO
      binding. We measured the heme coordination dynamics in the picosecond to second
      time range and identified Met80 and NO rebinding phases using time-resolved Raman
      and absorption spectroscopies. Dissociation of NO instantly produces 5-coordinate
      heme with a domed structure which continues to rearrange within 15 ps, while the
      initial ruffling distortion disappears. The rates of Cyt c-NO complex formation
      measured by transient absorption are kon = 1.81 * 106 M-1 s-1 for ferric Cyt c
      and 83 M-1 s-1 for ferrous Cyt c. After NO dissociation and exit from the heme
      pocket, the rebinding of Met80 to the heme iron takes place 6 orders of magnitude
      more slowly (3-5 MUs) than Met80 rebinding in the absence of NO (5 ps).
      Altogether, these data reveal the structural and dynamic properties of Cyt c in
      interaction with nitric oxide relevant for the molecular mechanism of apoptosis.

PMID- 28759068
TI  - Remote-control of the enantiomeric supramolecular recognition mediated by chiral
      azobenzenes bound to human serum albumin.
AB  - Three novel tyrosine-conjugated azobenzene molecules were designed and their
      ability to target a natural chiral host matrix (human serum albumin, HSA) was
      investigated. We found that the interplay between the spatial configuration of
      the chiral substituents and the change in local symmetry resulting from the
      photoisomerization process strongly affects the optical activity of the bound
      photochromes. In particular, the different signal amplification obtained upon
      binding of the photoswitches to the biopolymer enables obtaining a chirooptical
      system tunable over a wide range of wavelengths.

PMID- 28759069
TI  - The mechanism for the formation of OH radicals in condensed-phase water under
      ultraviolet irradiation.
AB  - Irradiation on liquid water and ice by ultraviolet light in the range of 150-200
      nm can create volatile OH radicals which react with other organic and inorganic
      molecules actively. However, the mechanism for OH radical formation in the
      condensed-phase water in this energy range is still unclear. To uncover this
      mechanism we studied the excited-state behaviors of ice using first-principles
      calculations based on many-body Green's function theory. First, we showed that
      the long-wavelength optical absorption at the Urbach tail (190-300 nm) can be
      attributed to inherent hydroxide ions or transient structures formed in the
      autoionization process. Second, we revealed that creation of the OH radicals can
      be attributed to two mechanisms. Irradiation by the light at the Urbach tail
      excites an electron out of the hydroxide ion, leaving a neutral OH radical
      behind. By the light around 150 nm, OH radicals can be produced barrierlessly via
      direct water photolysis through concerted proton and electron transfer. Our
      results provide valuable insights into the excited-state dynamics of condensed
      phase water, helping us understand in depth the photocatalytic reactions,
      radiation biology and chemistry.

PMID- 28759070
TI  - Long-lived excited states in metal clusters.
AB  - Bare metal clusters have properties that make them interesting for applications
      in photochemistry and photovoltaics. Long-lived excited states are a prerequisite
      for such applications, because in them the energy of the photon can be stored.
      Clusters have a low density of states and long-lived excited states should
      therefore occur frequently. However, in fact, such states are a rarity, as
      indicated by time-resolved photoelectron data of mass-selected cluster anions.
      And there is another puzzling observation: only clusters with narrow peaks in
      their photoelectron spectra exhibit long-lived excited states. Both findings can
      be explained if internal conversion, i.e. the conversion of electronic excitation
      energy into vibrational excitations, is the major relaxation mechanism in
      clusters. It becomes more likely, if a change of the electronic configuration
      results in a large geometry change, which is probably the case for most clusters.
      Only clusters with a weak coupling between geometric and electronic structure may
      have long-lived excited states and narrow peaks.

PMID- 28759071
TI  - Current-voltage characteristics of borophene and borophane sheets.
AB  - Motivated by recent experimental and theoretical research on a monolayer of boron
      atoms, borophene, the current-voltage characteristics of three different
      borophene sheets, 2Pmmn, 8Pmmn, and 8Pmmm, are calculated using density
      functional theory combined with the nonequilibrium Green's function formalism.
      Borophene sheets with two and eight atoms in a unit cell are considered. Their
      band structure, electron density, and structural anisotropy are analyzed in
      detail. The results show that the 8Pmmn and 8Pmmm structures that have eight
      atoms in the unit cell have less anisotropy than 2Pmmn. In addition, although
      8Pmmn shows a Dirac cone in the band structure, its current is lower than that of
      the other two. We also consider a fully hydrogenated borophene, borophane, and
      find that the hydrogenation process reduces the structural anisotropy and the
      current significantly. Our findings reveal that the current-voltage
      characteristics of the borophene sheets can be used to detect the type and the
      growth direction of the sample because it is strongly dependent on the direction
      of the electron transport, anisotropy, and details of the unit cell of the
      borophene.

PMID- 28759072
TI  - Mechanical properties and electronic structure of edge-doped graphene nanoribbons
      with F, O, and Cl atoms.
AB  - In this study, we present the structural, electronic, and mechanical properties
      of edge-doped zigzag graphene nanoribbons (ZGNRs) doped with fluorine, oxygen,
      and chlorine atoms. To the best of our knowledge, to date, no experimental
      results concerning the mechanical properties of graphene-derived nanoribbons have
      been reported in the literature. Simulations indicate that Cl- and F-doped ZGNRs
      present an equivalent 2-dimensional Young's modulus E2D, which seems to be higher
      than those of graphene and H-doped ZGNRs. This is a consequence of the electronic
      structure of the system, particularly originating from strong interactions
      between the dopant atoms localized at the edges. The interaction between dopant
      atoms located at the edges is higher for Cl and lower for F and O atoms. This is
      the origin of the observed trend, in which E > E > E for all the analyzed ZGNRs.

PMID- 28759074
TI  - Fabrication of photoluminescent nc-Si:SiO2 thin films prepared by PLD.
AB  - In the present report, the structural, compositional, morphological, and
      photoluminescence properties of nanostructured non-stoichiometric silicon oxide
      (nc-Si:SiO2 or SiOx) thin films fabricated by pulsed-laser ablation of silicon in
      the presence of oxygen pressure, from 10-4 to 0.5 mbar, are presented. X-ray
      diffraction spectra and Raman spectra confirmed the formation of nanocrystalline
      Si within the films while electron diffraction X-ray spectroscopy confirmed the
      increase in oxygen content with increasing O2 pressure. Scanning electron
      microscopy images of the SiOx films showed spreading of the micron-sized clusters
      on the otherwise uniform background, while Raman maps confirm the presence of
      nanocrystalline Si in these clusters embedded in a uniform matrix comprising
      oxidized amorphous silicon. A systematic blue shift in the band gap energy from
      1.55 to 2.80 eV was observed with increasing O2 pressure in the SiOx films due to
      a shift in the stoichiometry of the films from x = 0.03 to 2.14 respectively. The
      films with higher oxygen content exhibited broad and intense PL emissions with
      multiple peaks originating from quantum confined (QC) Si nanocrystals as well as
      oxygen defects like NBOH and VO centers. The variation in PL intensity as a
      function of excitation intensity displays an initial linear increase followed by
      saturation, a characteristic feature of emissions from QC nc-Si.

PMID- 28759075
TI  - Nickel-catalyzed C-H activation of purine bases with alkyl halides.
AB  - C-H alkylations of purine nucleosides were achieved by means of user-friendly
      nickel catalysis with ample substrate scope and high levels of chemo, site and
      regio control, which among others enabled the direct fluorescent labeling of
      purines in terms of late stage diversification.

PMID- 28759073
TI  - Defective ATP breakdown activity related to an ENTPD1 gene mutation demonstrated
      using 31P NMR spectroscopy.
AB  - The ecto-nucleoside triphosphate diphosphohydrolase-1 (E-NTPDase-1, CD39) enzyme
      is responsible for the breakdown of extracellular ATP to ADP and then to AMP by a
      two-step process. Defective CD39 activity has been described in a variety of
      medical conditions including malignancy and rheumatic diseases and has been
      proved to be of major diagnostic and clinical importance. Here we show for the
      first time that a 31P NMR spectroscopy methodology enables the quantification of
      these two steps in a single blood sample. We have applied this assay to determine
      the E-NTPDase activity on human mononuclear cells taken from two siblings
      affected by a stop-codon mutation in the ENTPD1 gene, their obligatory
      heterozygous parents, and healthy volunteers. The affected subjects presented low
      ATP breakdown activity, mainly expressed as low AMP production.

PMID- 28759076
TI  - Multiscale molecular simulations on interfacial adsorption and permeation of
      nanoporous graphynes.
AB  - Graphyne has been proposed as a distinctive molecular sieving membrane due to its
      intrinsic nanoscale pores and single-atom thickness. However, this novel
      application requires a precise quantification and understanding of the molecular
      interaction at graphyne interfaces, which can modulate molecular transport across
      graphyne. Herein, interfacial adsorption and permeation of ethanol-water mixtures
      on graphynes are studied by a multiscale simulation strategy, in which dispersion
      corrected density functional theory (DFT-D) and classical molecular dynamics (MD)
      are combined. Our results show that graphyne possesses differential surface
      affinities with ethanol and water, provoking a preferential adsorption layer of
      ethanol. The adsorption on the graphyne surface is dominated by attractive
      dispersion force, even for polar water molecules. As a joint function of ethanol
      rich segregation adsorption on graphyne and preferred pore occupation of ethanol,
      polyporous graphyne with a suitable pore size is envisioned to act as an alcohol
      permselective membrane. Our simulation results present new insights into
      interfacial interaction and have an impact on the promising application of two
      dimensional graphyne membranes.

PMID- 28759077
TI  - A highly conductive carbon-sulfur film with interconnected mesopores as an
      advanced cathode for lithium-sulfur batteries.
AB  - A highly conductive graphene sheet-mesoporous carbon (MC) sphere/active sulfur
      (GMC-S) film, with MC-sulfur spheres as "active islands" and graphene sheets as
      "trapping nets", exhibits good cycling stability (500 cycles, with a capacity
      retention of 85%) with a high specific capacity of 1322 mA h g-1 at 0.1C.

PMID- 28759078
TI  - Mechanochemically-assisted solid-state photocatalysis (MASSPC).
AB  - In this proof-of-concept study, we demonstrate the first successful transfer of
      transition metal-free photocatalysis from the conventional solution environment
      into the solid state, which is enabled by simultaneous irradiation with visible
      light and mechanochemical ball milling.

PMID- 28759079
TI  - Catalytic role of vacancy diffusion in ceria supported atomic gold catalyst.
AB  - Dynamics of intrinsic defects are considered fundamental in the chemistry of
      reducible oxides, and their effect on catalytic reactions have been rarely
      reported. Herein, we propose a new Ov diffusion assisted Langmuir-Hinshelwood
      mechanism for CO oxidation, which may largely account for the origin of high
      reactivity of supported atomic gold catalysts.

PMID- 28759080
TI  - The role of curvature effects in liquid-liquid extraction: assessing organic
      phase mesoscopic properties from MD simulations.
AB  - The bending rigidity of small reverse aggregates involved in liquid-liquid
      extraction processes has been investigated by molecular dynamics simulations.
      Simulations of a common extractant (DMDOHEMA) with four hydrophobic chains in
      explicit solvent (n-heptane) and in vacuum have been performed to determine the
      effect of solvent penetration on film stiffness. Elastic film bending energy that
      is needed for mesoscopic modelling of transfer of species between complex fluids
      is harmonic in terms of curvature (Helfrich formalism) and the packing parameter
      only if the solvent is explicitly taken into account. In terms of the packing
      parameter of the real molecular film constituting the reverse water in oil
      aggregates and taking into account molecular volume, area and film thickness
      (that is in agreement with Tanford's model), the bending rigidity is calculated
      to be about 16 kBT per extractant molecule (about 40 kJ mol-1), which is smaller
      than the free energy of transfer from an isolated "monomer" molecule to a weak
      aggregate, but of the order of magnitude of the free energy of transfer used in
      liquid-liquid extraction processes.

PMID- 28759081
TI  - Polarity control of GaN epitaxial films grown on LiGaO2(001) substrates and its
      mechanism.
AB  - The polarity of GaN epitaxial films grown on LiGaO2(001) substrates by pulsed
      laser deposition has been well controlled. It is experimentally proved that the
      GaN epitaxial films grown on nitrided LiGaO2(001) substrates reveal Ga-polarity,
      while the GaN epitaxial films grown on non-nitrided LiGaO2(001) substrates show N
      polarity. The growth mechanisms for these two cases are systematically studied by
      first-principles calculations based on density functional theory. Theoretical
      calculation presents that the adsorption of a Ga atom preferentially occurs at
      the center of three N atoms stacked on the nitrided LiGaO2(001) substrates, which
      leads to the formation of Ga-polarity GaN. Whereas the adsorption of a Ga atom
      preferentially deposits at the top of a N atom stacked on the non-nitrided
      LiGaO2(001) substrates, which results in the formation of N-polarity GaN. This
      work of controlling the polarity of GaN epitaxial films is of paramount
      importance for the fabrication of group-III nitride devices for various
      applications.

PMID- 28759082
TI  - Persistent left superior vena cava.
AB  - Persistent left superior vena cava (PLSVC) is the most common congenital
      malformation of thoracic venous return and is present in 0.3 to 0.5% of
      individuals in the general population. This heart specimen was dissected from a
      35-year-old male cadaver whose cause of death was determined as non-cardiac. The
      heart was examined and we found a PLSVC draining into the coronary sinus. The
      right superior vena cava was present with a small-diameter ostium. An anomalous
      pulmonary vein pattern was observed; there was a common trunk to the left
      superior and left inferior pulmonary veins (diameter 17.8 mm) and an additional
      middle right pulmonary vein (diameter 2.7 mm) with two classic right pulmonary
      veins. The PLSVC draining into the coronary sinus had led to its enlargement,
      which could have altered the cardiac haemodynamics by significantly reducing the
      size of the left atrium and impeding its outflow via the mitral valve.

PMID- 28759083
TI  - A rare cause of early repolarisation in an adolescent boy with chest pain:
      myocardial bridging.
AB  - Early repolarisation is a common electrocardiographic (ECG) finding characterised
      by J-point and ST segment elevation >= 0.1 mV in two or more adjacent leads. The
      ECG pattern of early repolarisation is relatively common in asymptomatic
      subjects. Early repolarisation pattern may be seen in secondary conditions such
      as hypothermia, autonomic nervous system disturbances, cocaine abuse,
      hypercalcaemia and myocardial ischaemia. We present a case of an adolescent boy
      with chest pain and concurrent ST-segment elevation. Early repolarisation pattern
      was observed in the inferior leads of the ECG with increased troponin levels. He
      was shown to have myocardial bridging of the left anterior descending artery. The
      coronary anomaly was not associated with left ventricular hypertrophy. He was
      asymptomatic and the ECG changes normalised on the third day after admission. The
      patient was restricted from strenuous exertion and metoprolol was prescribed for
      prophylaxis.

PMID- 28759084
TI  - Radiation safety: time to act.

PMID- 28759085
TI  - Resveratrol did not alter blood pressure in rats with nitric oxide synthase
      inhibited hypertension.
AB  - BACKGROUND: Inhibition of nitric oxide synthase (NOS) is a well-known
      experimental model of hypertension (HT). It was shown that oxidative stress
      contributes to the pathogenesis of HT. Resveratrol is a potent anti-oxidant that
      is found in red grapes, peanuts and red wine. It improves the NO response and
      increases endothelial NOS expression, which causes endothelium-dependent
      vasorelaxation as well as renal vasodilation. We aimed to explore the effects of
      resveratrol on blood pressure, the water-salt balance and sodium excretion as a
      reflection of renal function in NOS-inhibited rat models. METHODS: Thirty-five
      male Sprague-Dawley rats (200-250 g) were used in this study. In order to obtain
      hypertension models, an NOS inhibitor, N-nitro-L-arginin (L-NNA) was used. The
      rats were randomly divided into five groups: controls (given water and 0.8% salty
      diet) and four groups [given L-NNA, resveratrol (RSV) eluent, RSV, and L-NNA +
      RSV]. Blood pressures were measured indirectly by the tailcuff method on the
      first, seventh and 10th days. At the end of the study protocol (10th day), fluid
      balance, glomerular filtration rate, fractional sodium excretion, and blood and
      urine sodium and creatinine levels were measured. RESULTS: At the end of the
      study protocol, blood pressures were higher in only the L-NNA group (117.8 +/-
      3.5 vs 149.5 +/- 2.1 mmHg; p < 0.05), as expected. Additional applications of RSV
      with L-NNA could not prevent the increase in blood pressure (122.8 +/- 7.3 vs
      155.4 +/- 4.4 mmHg; p < 0.05). There were no remarkable changes in water-salt
      balance and renal function with the application of resveratrol. CONCLUSION:
      Resveratrol was unable to prevent or reverse blood pressure increase in NOS
      inhibited rats.

PMID- 28759086
TI  - Assessment of myocardial repolarisation parameters in patients with familial
      Mediterranean fever.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is a chronic, recurrent auto
      inflammatory disease characterised by self-terminating attacks of fever and
      sterile polyserositis. The main cause of death in auto-inflammatory diseases is
      cardiovascular events. Additionally, auto-inflammatory diseases have potential
      effects on the myocardial repolarisation parameters, including the T-wave peak-to
      end (Tp-Te) interval, cTp-Te interval (corrected Tp-Te) and the cTp-Te/QT ratio.
      The aim of this study was to analyse the efficacy of myocardial repolarisation
      alterations in anticipation of cardiovascular risks in patients with FMF.
      METHODS: This study included 66 patients with FMF and 58 healthy control
      subjects. Tp-Te and cTp-Te intervals and the cTp-Te/QT ratio were measured from
      the 12-lead electrocardiogram. RESULTS: In electrocardiographic parameters,
      analysis of QT, QT dispersion, corrected QT (QTc) and QTc dispersion were similar
      between the groups. The Tp-Te and cTp-Te intervals and Tp-Te/QT and cTp-Te/QT
      ratios were significantly prolonged in FMF patients. Multivariate linear
      regression analyses indicated that erythrocyte sedimentation rate was an
      independent predictor of a prolonged cTp-Te interval. CONCLUSIONS: Our study
      revealed that when compared with control subjects, Tp-Te and cTp-Te intervals and
      cTp-Te/QT ratio were increased in FMF patients.

PMID- 28759087
TI  - Saliva/serum ghrelin, obestatin and homocysteine levels in patients with
      ischaemic heart disease.
AB  - BACKGROUND: We aimed to compare ghrelin, obestatin, homocysteine (Hcy), vitamin
      B12 and folate levels in the serum and saliva of ischaemic heart disease
      patients. METHODS: Serum and saliva were collected from 33 ischaemic heart
      disease (IHD) patients and 28 age- and body mass index-matched healthy
      individuals. Levels of acylated and desacylated ghrelin, obestatin and Hcy were
      determined using the ELISA method. RESULTS: Acylated ghrelin, desacylated ghrelin
      and obestatin levels in the saliva were found to be higher than those in the
      serum of the control group, while acylated and desacylated ghrelin levels in the
      saliva were significantly lower than those in the serum. Obestatin levels were
      higher in IHD patients (p = 0.001). Saliva and serum vitamin B12 and folate
      levels in IHD patients were significantly lower than in the control group (p =
      0.001). CONCLUSIONS: It was determined that serum ghrelin levels increased in
      ischaemic heart disease patients, while serum levels of obestatin decreased.

PMID- 28759088
TI  - The effects of treatment in patients with childhood asthma on the elastic
      properties of the aorta.
AB  - INTRODUCTION: The study aimed to investigate the effects of treatment in patients
      with childhood asthma on the elastic properties of the aorta and cardiovascular
      risk. METHODS: The study was performed in 66 paediatric patients diagnosed with
      bronchial asthma (BA). All patients were administered the beta2 agonist,
      salbutamol, for seven days, followed by one month of montelukast and six months
      of inhaled steroid treatment. All patients underwent conventional transthoracic
      echocardiographic imaging before and after treatment. Aortic elasticity
      parameters were considered to be the markers of aortic function. RESULTS: Aortic
      elasticity parameters, including aortic strain (15.2 +/- 4.8 and 18.8 +/- 9.5%, p
      = 0.043), aortic distensibility (7.26 +/- 4.71 and 9.53 +/- 3.50 cm2/dyn, p =
      0.010) and aortic stiffness index (3.2 +/- 0.6 and 2.8 +/- 0.5, p = 0.045 showed
      significant post-treatment improvement when compared to pre-treatment values.
      Tricuspid annular plane systolic excursion (TAPSE) was also observed to improve
      after treatment (1.81 +/- 0.38 and 1.98 +/- 0.43, p = 0.049). CONCLUSION: The
      study demonstrated that when provided at appropriate doses, medications used in
      BA may result in an improvement in aortic stiffness.

PMID- 28759089
TI  - Training community health workers to screen for cardiovascular disease risk in
      the community: experiences from Cape Town, South Africa.
AB  - : This article describes a training process to equip community health workers
      (CHWs) with knowledge and skills to identify individuals at high risk for
      cardiovascular disease (CVD) in a township in Cape Town. METHODS: CHWs were
      employed by a non-governmental organisation (NGO) primarily focusing on non
      communicable diseases (NCDs). They were trained in the theory of CVD, including
      physiological changes and related risk factors and in obtaining anthropometric
      and blood pressure measurements. Pre- and post-training tests assessed learning
      needs and the effectiveness of imparting knowledge about CVD, respectively.
      RESULTS: Training increased knowledge about CVD risk factors. CHWs were able to
      screen and identify those at risk for CVD and refer them to health professionals
      for validation of scores. The initial one-week training was too short, given the
      amount of information covered. Some CHWs had difficulty with English as the
      primary instruction medium and as the only language in which tests were offered.
      CONCLUSION: Although CHWs could be trained to screen for CVD risk, increased
      training time was required to impart the knowledge. The language used during
      training and testing presented challenges for those trainees whose dominant,
      spoken language was not English.

PMID- 28759090
TI  - A Path to Osteopathic Distinction: The Touro California GROUPIE Program.

PMID- 28759091
TI  - Fundamentals for an Osteopathic Obesity Designed Study: The Effects of Education
      on Osteopathic Medical Students' Attitudes Regarding Obesity.
AB  - Context: Obesity is a major health concern in the United States, and its
      prevalence continues to rise. Although it is a common health issue, many people,
      including health care professionals, are biased against people with obesity.
      Objective: To determine whether a comprehensive obesity curriculum presented to
      students in medical school can positively influence their attitudes toward
      obesity. Methods: The study was designed around a comprehensive educational
      obesity curriculum at Touro University College of Osteopathic Medicine-CA,
      involving the classes of 2013 through 2018. A survey to assess student attitudes
      toward obesity was distributed to first-year students before the curriculum,
      directly after completion, and each year after until graduation (graduating
      classes of 2015 through 2018). Second- and third-year medical students in 2011
      (graduating classes of 2014 and 2013), who did not complete the curriculum, were
      given an examination to establish baseline values and served as the control
      group. The obesity curriculum consisted of lectures delivered during the first
      and second year of medical school and case study simulations during the third
      year. Knowledge gained from the curriculum was assessed with a multiple-choice
      examination, and bias was assessed using the Fat Phobia Scale. Results: A total
      of 718 first- through fourth-year students were included. Students who completed
      the first year of the obesity curriculum (n=528) showed significantly greater
      medical knowledge regarding obesity-related epidemiology, pathogenesis,
      biochemistry, pathophysiology, and metabolic factors; nutrition, diet, physical
      activity, self-control, and behavior modification; pharmacologic and
      nonpharmacologic interventions; and associated chronic disorders, based on their
      multiple-choice examination scores compared with the control group. The
      examination scores indicated significant increases in medical knowledge compared
      with the precurriculum cohort after the curriculum (OMS I students: 130 [72.4%];
      133 [92.6%]; 133 [91.1%]; 132 [89.0%]; vs control: 105 [47.2%]; 134 [52.6%],
      respectively [P<.01]). In all 4 years observed, there was a significant reduction
      in bias among first-year medical students after obesity curriculum (before: 3.65,
      3.76, 3.57, 3.61, and after: 3.47, 3.38, 3.34, 3.37, respectively) (P<.05). The
      reduction in bias was also significantly sustained throughout the fourth year.
      Conclusion: A comprehensive obesity curriculum throughout medical school resulted
      in an improvement in students' attitudes toward and knowledge of obesity.

PMID- 28759092
TI  - Clinical Preceptors' Perceptions of Empathy: The Empathy in Osteopathic Training
      and Education (EMOTE) Study.
AB  - Context: Physician empathy influences rapport with patients and improves
      outcomes, but it is not well understood as an outcome of osteopathic medical
      education. Objective: To determine how clerkship preceptors at Touro University
      College of Osteopathic Medicine-CA (TUCOM) in Vallejo define empathy and how they
      compare observed empathetic behavior of TUCOM students with that of other medical
      students. Methods: Cross-sectional data were obtained from a survey of TUCOM
      clinical preceptors comparing TUCOM students with other medical students on 10
      behaviors. Results were analyzed with a 2-tailed z test of proportional
      difference at the 95% confidence level. Results: Of 650 preceptors contacted, 177
      responded and were included in the final analysis (27%). Survey item reliability
      was high (Cronbach alpha=0.96). A majority of preceptors (59% to 71%) considered
      TUCOM students "similar" to other medical students for each behavior. A majority
      of preceptors (107 [60%]) shared a definition of empathy with one another and
      with the National Board of Osteopathic Medical Examiners and the American
      Association of Colleges of Osteopathic Medicine. Approximately 39% of preceptors
      rated TUCOM students "better" or "advanced" for "displays of empathy" compared
      with approximately 30% of preceptors who rated students as better or advanced
      across all 10 behaviors. Preceptors who shared a definition of empathy rated
      TUCOM students as better or advanced at a significantly higher rate for "displays
      of empathy" (z=1.982, P<.05) compared with preceptors who did not share a
      definition (n=70). Osteopathic preceptors (n=67) rated TUCOM students
      significantly higher on "displays of empathy" (z=2.82, P<.05) and "clear and
      effective communication to patients, families and co-workers" (z=2.83, P<.01)
      than did allopathic preceptors. No significant differences were found based on
      number of years as a preceptor or on the combination of types of students the
      preceptor taught. Conclusion: Most clinical preceptors shared a definition of
      empathy, and they were able to observe and rate displays of it in clerkship
      students. Preceptors rated TUCOM students more favorably than other students they
      taught for displays of empathy.

PMID- 28759093
TI  - Functional Somatic Syndrome: Assessment and Management.
AB  - Functional somatic syndrome (FSS) occurs in as many as 30% of patients in general
      medical practice, but it is infrequently a topic of formal instruction. Many
      physicians feel uncomfortable with medically unexplained symptoms and are
      unfamiliar with how to assess or manage them. Traditional medical approaches can
      be ineffective and can contribute to iatrogenic or adverse physiologic effects in
      patients. Physicians treating patients with FSS should not only consider standard
      medical tests, but they should also try to gain a deeper behavioral understanding
      of the mind-body connections that underlie the presenting symptoms. Osteopathic
      physicians, with their emphasis on holistic patient care, are in a key position
      to treat patients with FSS. This review provides a brief recapitulation of the
      literature and illustrates key factors in the assessment and management of FSS.

PMID- 28759094
TI  - Conversion of Sugar to Fat: Is Hepatic de Novo Lipogenesis Leading to Metabolic
      Syndrome and Associated Chronic Diseases?
AB  - Epidemiologic studies suggest a link between excess sugar consumption and
      obesity, fatty liver disease, metabolic syndrome, and type 2 diabetes mellitus.
      One important pathway that may link these metabolic diseases to sugar consumption
      is hepatic conversion of sugar to fat, a process known as de novo lipogenesis
      (DNL). Mechanistic studies have shown that diets high in simple sugars increase
      both DNL and liver fat. Importantly, removal of sugar from diets of children with
      obesity for only 9 days consistently reduced DNL and liver fat and improved
      glucose and lipid metabolism. Although the sugar and beverage industries continue
      to question the scientific evidence linking high-sugar diets to metabolic
      diseases, major health organizations now make evidence-based recommendations to
      limit consumption of simple sugars to no more than 5% to 10% of daily intake.
      Clear recommendation about moderating sugar intake to patients may be an
      important nonpharmacologic tool to include in clinical practice.

PMID- 28759095
TI  - Ready for Residency: A Bloomian Analysis of Competency-Based Osteopathic Medical
      Education.
AB  - Context: Bloom's Taxonomy is a widely accepted tool for analyzing learning
      objectives, creating assessment materials, and ensuring that students move
      progressively through various levels of knowledge and cognition. Competency-based
      osteopathic medical education has, to the authors' knowledge, yet to be subjected
      to systematic bloomian analysis. Objective: To advance a bloomian analysis of
      competencies published by the American Association of Colleges of Osteopathic
      Medicine (AACOM) and draw consequences of that analysis for undergraduate
      osteopathic medical education. Methods: Content analysis of the verbs and
      contexts used in the AACOM competencies was conducted, followed by categorization
      by the various cognitive and knowledge dimensions as specified by the Revised
      Bloom's Taxonomy. Results: The majority of AACOM competencies gravitate toward
      the taxonomy's apply and procedural cognitive and knowledge dimensions,
      respectively. In addition, 58% of the top 10 most-used verbs in the document were
      identified to be in the apply cognitive dimension. An analysis of the
      competencies revealed that 69% can be categorized under the procedural knowledge
      dimension. Of 657 code co-occurances, 45% were from the apply cognitive and
      procedural knowledge dimensions. These figures suggest a skewing toward
      application-based cognitive and procedural-based knowledge over other types of
      cognitive and knowledge dimensions. Conclusion: Bloom's Taxonomy offers a useful
      framework for understanding how competency-based osteopathic medical education is
      organized. Such analysis underscores the importance of attending to the language
      and construction of competencies to better understand how the language of
      competencies shapes pedagogic practices and begin a broader conversation about
      the appropriate use and distribution of lower- and higher-order cognitive
      processes within competency-based osteopathic medical education.

PMID- 28759096
TI  - Pheochromocytoma-Induced Cardiomyopathy Mimicking Acute Coronary Syndrome.
AB  - Pheochromocytoma is a rare catecholamine-secreting tumor with a prevalence of
      0.1% to 0.6% in hypertensive patients. The classic triad of symptoms is headache,
      palpitations, and diaphoresis, but clinical presentation varies greatly.
      Pheochromocytoma can also mimic acute coronary syndrome and heart failure. With
      surgical resection, appropriate preoperative medical therapy, and 10% malignancy
      rate, prognosis is usually good. In the present case, a patient presented to the
      emergency department with symptoms suggesting a non-ST-segment elevation
      myocardial infarction and was transferred to a tertiary medical center for a
      cardiac catheterization. No coronary artery disease was found. However,
      cardiomyopathy developed, which made pheochromocytoma difficult to diagnose at
      first glance.

PMID- 28759097
TI  - Vanishing Lung Syndrome.

PMID- 28759098
TI  - Obliterated Temporomandibular Joint.

PMID- 28759099
TI  - Effects of Clinical Exposure to Osteopathic Manipulative Medicine on Confidence
      Levels of Medical Students.
AB  - Context: Training in osteopathic manipulative medicine (OMM) is a unique
      component of the osteopathic medical school curriculum. Indicators of successful
      OMM programming include student comfort in explaining and performing OMM as well
      as confidence in using OMM on future patients. Research on the amount of clinical
      exposure sufficient to achieve this goal is limited. Objectives: To gauge the
      impact of clinical OMM exposure on medical students' self-assessed understanding
      of OMM, their ability to discuss, explain, and perform OMM, and their plan to use
      OMM in their future practice. Methods: Fourth-year osteopathic medical students
      were e-mailed surveys before (baseline), during, and after 4 weeks (postrotation)
      of an elective OMM rotation. Answers were scaled from 0 to 10, with 0 being not
      at all comfortable/confident and 10 being the most comfortable/confident.
      Results: Thirty-five students participated in the survey. A significant mean (SD)
      increase was found between the baseline and postrotation scores for students'
      understanding of OMM principles (1.43 [0.51]; P<.001), comfort discussing OMM
      principles with patients (1.27 [0.88]; P<.001), comfort with explaining OMM to
      someone unfamiliar with it (1.32 [0.82]; P<.001), comfort with performing an
      osteopathic structural examination (2.23 [1.44]; P<.001), and confidence
      incorporating OMM into future practice (1.86 [0.47]; P<.001). Conclusion:
      Increased clinical exposure to OMM increased the confidence of osteopathic
      medical students in all dimensions surveyed. This observation can help guide the
      development of undergraduate osteopathic clinical programming as well as
      standards for entry of allopathic residents into ACGME programs with osteopathic
      designation.

PMID- 28759100
TI  - Multiple Basal Cell Carcinoma Arising in a Verrucous Epidermal Naevus: Clinical,
      Histological and Therapeutic Observations.

PMID- 28759101
TI  - Bone Formation in Cutaneous Nodules on the Leg: A Quiz. Osteogenic cutaneous
      metastases in malignant melanoma.

PMID- 28759102
TI  - A biaxial strain-based expansion mechanism for auxetic stent deployment.
AB  - BACKGROUND: Auxetics, a special class of materials, tend to expand both in the
      radial and longitudinal directions when a unidirectional tensile force is
      applied. Recently, studies have come up with new designs for auxetic vascular and
      nonvascular stents which are deployed with commercial balloon catheters. There
      are some inherent limitations associated with a unidirectional application of
      expansion force in the effective deployment of stents. This work proposed a
      solution to some of these limitations through the use of a biaxial mode of a
      predetermined strain-based expansion mechanism. METHOD: The design incorporated a
      pressure-activated crank-slider mechanism. Fabrication of a prototype for
      experimental verification was carried out through milling and high-speed lathe
      machining. The testing of the device employed the use of auxetic stents,
      fabricated from a biocompatible polymer. A finite element study is presented to
      extrapolate experimental results to a broader range of operation and working
      conditions. RESULTS AND CONCLUSIONS: The expansion mechanism is similar in
      operation to the opening of an umbrella. The length of the connected auxetic
      stent increases when internal hydraulic pressure is applied. The degree of linear
      expansion in 1 direction influences the expansion of auxetic stent in the lateral
      direction. As the device exerts pressure longitudinally, a larger amount of the
      force is distributed on the unit cells/hinges which ultimately results in an
      increased expansion of the stent.

PMID- 28759103
TI  - Contribution of solid organ transplant recipients to the pediatric non-hodgkin
      lymphoma burden in the United States.
AB  - BACKGROUND: Pediatric solid organ transplant recipients have a 100 to 200 times
      higher risk of non-Hodgkin lymphoma (NHL) than the general pediatric population.
      Consequently, transplant-related NHL may contribute considerably to the pediatric
      NHL burden in the United States. METHODS: A cohort study using a linkage between
      the US transplant registry and 16 cancer registries was conducted. Cancer
      incidence rates were calculated for people less than 20 years old in the
      transplant and general populations. Rates were applied to transplant registry and
      US census data to estimate pediatric NHL counts for transplant recipients and the
      general population. RESULTS: During 1990-2012, an estimated 22,270 NHLs were
      diagnosed in US children and adolescents; they included 628 cases diagnosed in
      transplant recipients. Thus, 2.82% of pediatric NHL diagnoses in the general
      population (95% confidence interval [CI], 2.45%-3.19%) occurred in transplant
      recipients. Among transplant recipients, the most common subtypes were diffuse
      large B-cell lymphoma (DLBCL; 64.5% of cases) and Burkitt lymphoma (BL; 8.6%).
      For DLBCL and BL, transplant recipients contributed 7.62% (95% CI, 6.35%-8.88%)
      and 0.87% (95% CI, 0.51%-1.23%) of diagnoses, respectively. The proportion of
      NHLs that occurred in transplant recipients was highest among children less than
      5 years old (4.46%; 95% CI, 3.24%-5.69%) and in more recent calendar years (3.73%
      in 2010-2012; 95% CI, 2.07%-5.39%). DLBCL patterns were similar, with transplant
      recipients contributing 19.78% of cases among children less than 5 years old (95%
      CI, 12.89%-26.66%) and 11.4% of cases in 2010-2012 (95% CI, 5.54%-17.28%).
      CONCLUSIONS: Among children and adolescents, solid organ transplant recipients
      contribute a substantial fraction of NHL diagnoses, particularly DLBCL diagnoses.
      This fraction has increased over time. Prevention efforts targeted toward this
      group could reduce the overall pediatric NHL burden. Cancer 2017;123:4663-4671.
      (c) 2017 American Cancer Society.

PMID- 28759105
TI  - How are arbuscular mycorrhizal associations related to maize growth performance
      during short-term cover crop rotation?
AB  - BACKGROUND: Better cover crop management options aiming to maximize the benefits
      of arbuscular mycorrhizal fungi (AMF) to subsequent crops are largely unknown. We
      investigated the impact of cover crop management methods on maize growth
      performance and assemblages of AMF colonizing maize roots in a field trial. The
      cover crop treatments comprised Italian ryegrass, wheat, brown mustard and fallow
      in rotation with maize. RESULTS: The diversity of AMF communities among cover
      crops used for maize management was significantly influenced by the cover crop
      and time course. Cover crops did not affect grain yield and aboveground biomass
      of subsequent maize but affected early growth. A structural equation model
      indicated that the root colonization, AMF diversity and maize phosphorus uptake
      had direct strong positive effects on yield performance. CONCLUSION: AMF
      variables and maize performance were related directly or indirectly to maize
      grain yield, whereas root colonization had a positive effect on maize
      performance. AMF may be an essential factor that determines the success of cover
      crop rotational systems. Encouraging AMF associations can potentially benefit
      cover cropping systems. Therefore, it is imperative to consider AMF associations
      and crop phenology when making management decisions. (c) 2017 Society of Chemical
      Industry.

PMID- 28759106
TI  - Physicochemical and Sensory Properties of Cold Pressed Oils from Florida Hamlin
      and Valencia Oranges Affected by Huanglongbing.
AB  - Cold pressed oils from huanglongbing (HLB) symptomatic (SY) and asymptomatic (AS)
      Hamlin and Valencia oranges were assessed for 2 y (2014 to 2015 and 2015 to 2016
      seasons) with 2 harvest dates for each orange variety per year. Physicochemical
      properties (optical rotation, aldehyde content, ultraviolet [UV] absorbance,
      refractive index, and specific gravity) mandated by the United States
      Pharmacopeia (USP) for orange oil quality were assessed. Hamlin and Valencia oils
      showed minor differences in physicochemical properties based upon disease stage.
      However, all Hamlin oils had aldehyde contents below the USP minimum and Valencia
      oil from late season SY oranges had specific gravities above the USP maximum.
      Significant differences based on harvest year were seen for aldehyde content,
      refractive index, optical rotation, and UV absorbance. While none of these
      changes led to an oil being out of USP specifications, they indicate a need to
      monitor the quality of oil every year to ensure a consistent product. Flavor
      taste panels were performed both years by adding 0.035% oil samples to a uniform
      orange juice base. Aroma panels were done by smelling pure oil. There were no
      significant differences between SY and AS oils for flavor, although panelist race
      was a significant factor in several of the panels. There were significant
      differences between the aroma of SY and AS oils for both 2015 to 2016 Hamlin
      Early and Valencia Late samples. Overall, these results show HLB can have an
      effect on the aroma and USP mandated physicochemical properties of Florida orange
      oils, although flavor may be unaffected by this plant disease.

PMID- 28759104
TI  - The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral
      protection to spondyloarthritis.
AB  - The human leukocyte antigen class I gene HLA-B27 is the strongest risk factor for
      ankylosing spondylitis (AS), a chronic inflammatory arthritic disorder. More
      recently, the Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and 2 genes have been
      identified by genome wide association studies (GWAS) as additional susceptibility
      factors. In the ER, these aminopeptidases trim the peptides to a length suitable
      to fit into the groove of the major histocompatibility complex (MHC) class I
      molecules. It is noteworthy that an epistatic interaction between HLA-B27 and
      ERAP1, but not between HLA-B27 and ERAP2, has been highlighted. However, these
      observations suggest a paramount centrality for the HLA-B27 peptide repertoire
      that determines the natural B27 immunological function, i.e. the T cell antigen
      presentation and, as a by-product, elicits HLA-B27 aberrant behaviours: (i) the
      misfolding leading to ER stress responses and autophagy and (ii) the surface
      expression of homodimers acting as ligands for innate immune receptors. In this
      context, it has been observed that the HLA-B27 carriers, besides being prone to
      autoimmunity, display a far better surveillance to some viral infections. This
      review focuses on the ambivalent role of HLA-B27 in autoimmunity and viral
      protection correlating its functions to the quantitative and qualitative effects
      of ERAP1 and ERAP2 polymorphisms on their enzymatic activity.

PMID- 28759108
TI  - A call for action: Increasing enrollment of untreated patients with higher-risk
      myelodysplastic syndromes in first-line clinical trials.
AB  - Hypomethylating agents (HMAs) have changed the landscape of the management of
      patients with higher-risk myelodysplastic syndromes (HR-MDS). HMAs have improved
      hematopoiesis and quality of life and, in the case of azacitidine, prolonged
      survival in a large randomized trial. However, multiple real-life and registry
      analyses have demonstrated minimal survival gains at the population level after
      the approval of HMAs. Furthermore, the 24-month median survival observed with
      azacitidine in the landmark AZA-001 trial has not been replicated in population
      based studies or in other clinical trials using azacitidine monotherapy arms.
      Herein, we critically review the accumulating data suggesting that the actual
      survival impact of HMAs, especially azacitidine, in patients with HR-MDS is
      significantly lower than what was observed in the AZA-001 trial and what often is
      quoted to patients, and discuss the potential explanations for this discrepancy.
      We also present the rationale for why front-line clinical trial enrollment should
      be always considered and discussed with every newly diagnosed patient with HR-MDS
      rather than defaulting to the routine use of HMAs. Finally, we review the
      challenges to wider-scale enrollment in front-line HR-MDS clinical trials and
      suggest solutions to accelerate this process with the ultimate goal of achieving
      a real and substantial change in the natural history of this aggressive
      malignancy. Cancer 2017;123:3662-3672. (c) 2017 American Cancer Society.

PMID- 28759107
TI  - Low glycaemic index diets for the prevention of cardiovascular disease.
AB  - BACKGROUND: The glycaemic index (GI) is a physiological measure of the ability of
      a carbohydrate to affect blood glucose. Interest is growing in this area for the
      clinical management of people at risk of, or with, established cardiovascular
      disease. There is a need to review the current evidence from randomised
      controlled trials (RCTs) in this area. This is an update of the original review
      published in 2008. OBJECTIVES: To assess the effect of the dietary GI on total
      mortality, cardiovascular events, and cardiovascular risk factors (blood lipids,
      blood pressure) in healthy people or people who have established cardiovascular
      disease or related risk factors, using all eligible randomised controlled trials.
      SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL in July 2016. We
      also checked reference lists of relevant articles. No language restrictions were
      applied. SELECTION CRITERIA: We selected RCTs that assessed the effects of low GI
      diets compared to diets with a similar composition but a higher GI on
      cardiovascular disease and related risk factors. Minimum trial duration was 12
      weeks. Participants included were healthy adults or those at increased risk of
      cardiovascular disease, or previously diagnosed with cardiovascular disease.
      Studies in people with diabetes mellitus were excluded. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently screened and selected studies. Two review
      authors independently assessed risk of bias, evaluated the overall quality of the
      evidence using GRADE, and extracted data following the Cochrane Handbook for
      Systematic Reviews of Interventions. We contacted trial authors for additional
      information. Analyses were checked by a second reviewer. Continuous outcomes were
      synthesized using mean differences and adverse events were synthesized
      narratively. MAIN RESULTS: Twenty-one RCTs were included, with a total of 2538
      participants randomised to low GI intervention (1288) or high GI (1250). All 21
      included studies reported the effect of low GI diets on risk factors for
      cardiovascular disease, including blood lipids and blood pressure.Twenty RCTs (18
      of which were newly included in this version of the review) included primary
      prevention populations (healthy individuals or those at high risk of CVD, with
      mean age range from 19 to 69 years) and one RCT was in those diagnosed with pre
      existing CVD (a secondary prevention population, with mean age 26.9 years). Most
      of the studies did not have an intervention duration of longer than six months.
      Difference in GI intake between comparison groups varied widely from 0.6 to
      42.None of the included studies reported the effect of low GI dietary intake on
      cardiovascular mortality and cardiovascular events such as fatal and nonfatal
      myocardial infarction, unstable angina, coronary artery bypass graft surgery,
      percutaneous transluminal coronary angioplasty, and stroke. The unclear risk of
      bias of most of the included studies makes overall interpretation of the data
      difficult. Only two of the included studies (38 participants) reported on adverse
      effects and did not observe any harms (low-quality evidence). AUTHORS'
      CONCLUSIONS: There is currently no evidence available regarding the effect of low
      GI diets on cardiovascular disease events. Moreover, there is currently no
      convincing evidence that low GI diets have a clear beneficial effect on blood
      lipids or blood pressure parameters.

PMID- 28759110
TI  - Effects of early combinatorial treatment of autologous split-thickness skin
      grafts in red duroc pig model using pulsed dye laser and fractional CO2 laser.
AB  - BACKGROUND AND OBJECTIVE: The use of pulsed dye laser (PDL) and fractional CO2
      (FX CO2 ) laser therapy to treat and/or prevent scarring following burn injury is
      becoming more widespread with a number of studies reporting reduction in scar
      erythema and pruritus following treatment with lasers. While the majority of
      studies report positive outcomes following PDL or FX CO2 therapy, a number of
      studies have reported no benefit or worsening of the scar following treatment.
      The objective of this study was to directly compare the efficacy of PDL, FX CO2 ,
      and PDL + FX CO2 laser therapy in reducing scarring post burn injury and
      autografting in a standardized animal model. MATERIALS AND METHODS: Eight female
      red Duroc pigs (FRDP) received 4 standardized, 1 in. x 1 in. third degree burns
      that were excised and autografted. Wound sites were treated with PDL, FX CO2 , or
      both at 4, 8, and 12 weeks post grafting. Grafts receiving no laser therapy
      served as controls. Scar appearance, morphology, size, and erythema were assessed
      and punch biopsies collected at weeks 4, 8, 12, and 16. At week 16, additional
      tissue was collected for biomechanical analyses and markers for inflammatory
      cytokines, extracellular matrix (ECM) proteins, re-epithelialization,
      pigmentation, and angiogenesis were quantified at all time points using qRT-PCR.
      RESULTS: Treatment with PDL, FX CO2 , or PDL + FX CO2 resulted in significantly
      less contraction versus skin graft only controls with no statistically
      significant difference among laser therapy groups. Scars treated with both PDL
      and FX CO2 were visually more erythematous than other groups with a significant
      increase in redness between two and three standard deviations above normal skin
      redness. Scars treated with FX CO2 were visually smoother and contained
      significantly fewer wrinkles. In addition, hyperpigmentation was significantly
      reduced in scars treated with FX CO2 . CONCLUSIONS: The use of fractional carbon
      dioxide or pulsed dye laser therapy within 1 month of autografting significantly
      reduced scar contraction versus control, though no statistically significant
      difference was detected between laser modalities or use of both modalities.
      Overall, FX CO2 therapy appears to be modestly more effective at reducing
      erythema, and improving scar texture and biomechanics. The current data adds to
      prior studies supporting the role of laser therapy in the treatment of burn scars
      and indicates more study is needed to optimize delivery protocols for maximum
      efficacy. Lasers Surg. Med. 50:78-87, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 28759109
TI  - Probing the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway
      in gliomas: A phase 2 study of everolimus for recurrent adult low-grade gliomas.
AB  - BACKGROUND: Activation of the phosphatidylinositol 3-kinase (PI3K)/mammalian
      target of rapamycin (mTOR) pathway is common in patients with low-grade gliomas
      (LGGs), but agents that inhibit this pathway, including mTOR inhibitors, have not
      been studied in this population. METHODS: Fifty-eight patients with pathologic
      evidence of recurrence after they had initially been diagnosed with World Health
      Organization (WHO) grade II gliomas were enrolled into a prospective phase 2
      clinical trial and received daily everolimus (RAD001) for 1 year or until
      progression. Tissue at the time of enrollment was analyzed for markers of
      PI3K/mTOR pathway activation. Thirty-eight patients underwent serial
      multiparametric magnetic resonance imaging, with the tumor volume and the
      perfusion metrics (the fractional blood volume [fBV] for capillary density and
      the transfer coefficient [Kps ] for vascular permeability) measured during
      treatment. The primary endpoint was progression-free survival at 6 months (PFS-6)
      in patients with WHO II disease at enrollment. RESULTS: For patients with WHO II
      gliomas at enrollment, the PFS-6 rate was 84%, and this met the primary endpoint
      (P < .001 for an improvement from the historical rate of 17%). Evidence of
      PI3K/mTOR activation by immunohistochemistry for phosphorylated ribosomal
      S6Ser240/244 (p-S6Ser240/244 ) was associated with worse progression-free
      survival (PFS; hazard ratio [HR], 3.03; P = .004) and overall survival (HR, 12.7;
      P = .01). Tumor perfusion decreased after 6 months (median decrease in fBV, 15%;
      P = .03; median decrease in Kps , 12%; P = .09), with greater decreases
      associated with improved PFS (HR for each 10% fBV decrease, 0.71; P = .01; HR for
      each 10% Kps decrease, 0.82; P = .04). CONCLUSIONS: Patients with recurrent LGGs
      demonstrated a high degree of disease stability during treatment with everolimus.
      PI3K/mTOR activation, as measured by immunohistochemistry for p-S6, was
      associated with a worse prognosis. Tumor vascular changes were observed that were
      consistent with the antiangiogenic effects of mTOR inhibitors. These results
      support further study of everolimus for LGGs. Cancer 2017;123:4631-4639. (c) 2017
      American Cancer Society.

PMID- 28759111
TI  - Daily Mindful Responding Mediates the Effect of Meditation Practice on Stress and
      Mood: The Role of Practice Duration and Adherence.
AB  - OBJECTIVE: Although meditation practice is an important component of many
      mindfulness-based interventions (MBIs), empirical findings of its effects on
      psychological functioning are mixed and the mechanisms for the effects remain
      unclear. Responding with mindfulness (i.e., returning one's attention back to a
      nonjudgmental, present-oriented awareness) is a fundamental skill practiced in
      meditations. With repeated meditation practice, this skill is thought to become
      internalized and be applied to one's daily life. We thus hypothesized that the
      extent to which individuals responded to daily events with mindfulness would
      mediate the effects of meditation practice (instance, duration, and adherence to
      instructions) on psychological well-being. METHOD: Using a daily diary
      methodology, we tracked the meditation practice, use of mindful responding during
      the day, and psychological outcomes (perceived stress, negative and positive
      affect) of 117 mindfulness-based stress reduction program participants. RESULTS:
      We found that on days when participants meditated, they responded with greater
      mindfulness to daily events, which accounted for the beneficial effects of
      meditating on psychological outcomes. Furthermore, findings suggest that on
      meditation days, longer and more closely adhered meditation practices were
      independently associated with increases in mindful responding, which in turn were
      associated with better psychological outcomes. CONCLUSION: These results suggest
      that regular, longer, and more closely adhered meditation practice is an
      important component of MBIs, in part because it leads to responding more
      mindfully in daily life, which promotes well-being.

PMID- 28759112
TI  - Fluid replacement therapy for acute episodes of pain in people with sickle cell
      disease.
AB  - BACKGROUND: Treating vaso-occlusive painful crises in people with sickle cell
      disease is complex and requires multiple interventions. Extra fluids are
      routinely given as adjunct treatment, regardless of the individual's state of
      hydration with the aim of slowing or stopping the sickling process and thereby
      alleviating pain. This is an update of a previously published Cochrane Review.
      OBJECTIVES: To determine the optimal route, quantity and type of fluid
      replacement for people with sickle cell disease with acute painful crises. SEARCH
      METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
      Trials Register which comprises of references identified from comprehensive
      electronic database searches and handsearches of relevant journals and abstract
      books of conference proceedings.We also conducted searches of Embase (November
      2007), LILACS, www.ClinicalTrials.gov (05 January 2010), and the WHO ICTRP (30
      June 2017).Date of most recent search of the Group's Haemoglobinopathies Trials
      Register: 16 February 2017. SELECTION CRITERIA: Randomised and quasi-randomised
      controlled trials that compared the administration of supplemental fluids
      adjunctive to analgesics by any route in people with any type of sickle cell
      disease during an acute painful episode, under medical supervision (inpatient,
      day care or community). DATA COLLECTION AND ANALYSIS: No relevant trials have yet
      been identified. MAIN RESULTS: Sixteen trials were identified by the searches,
      all of which were not eligible for inclusion in the review. AUTHORS' CONCLUSIONS:
      Treating vaso-occlusive crises is complex and requires multiple interventions.
      Extra fluids, generally oral or intravenous, are routinely administered during
      acute painful episodes to people with sickle cell disease regardless of the
      individual's state of hydration. Reports of their use during these acute painful
      episodes do not state the efficacy of any single route, type or quantity of fluid
      compared to another. However, there are no randomised controlled trials that have
      assessed the safety and efficacy of different routes, types or quantities of
      fluid. This systematic review identifies the need for a multicentre randomised
      controlled trial assessing the efficacy and possible adverse effects of different
      routes, types and quantities of fluid administered to people with sickle cell
      disease during acute painful episodes.

PMID- 28759113
TI  - Feasibility and preliminary effects of resistance training and nutritional
      supplements during versus after radiotherapy in patients with head and neck
      cancer: A pilot randomized trial.
AB  - BACKGROUND: Patients with head and neck cancer (HNC) experience involuntary
      weight loss that has a negative impact on physical function, morbidity, and
      survival. The objective of the current study was to evaluate the feasibility of
      an exercise and nutrition intervention during radiotherapy (RT) compared with
      after RT, and to examine preliminary effects on skeletal muscle mass. METHODS:
      Patients with HNC were randomized to an exercise and nutrition intervention
      during RT (EN-DUR) or after RT (EN-AF). The EN-DUR intervention was conducted at
      a hospital and the EN-AF intervention took place at a rehabilitation center. The
      interventions consisted of progressive resistance training (PRT) and oral
      nutritional supplements (ONS). Feasibility outcomes were tracked weekly and
      muscle mass was measured by computed tomography scans before and after RT and at
      2 months follow-up. RESULTS: Of the 50 eligible patients, 41 (82%) agreed to
      participate. 90% of patients completed the EN-DUR intervention and the adherence
      to PRT and ONS was 81% and 57%, respectively. 52% of patients attended the EN-AF
      intervention and adherence to PRT and ONS was 94% and 76%, respectively. The EN
      DUR demonstrated a trend toward mitigating loss of muscle mass during RT and the
      EN-AF demonstrated a similar trend after RT. No difference in muscle mass was
      detected between the groups from baseline to week 14. CONCLUSIONS: An exercise
      and nutrition intervention is feasible for patients with HNC during RT, and the
      intervention is potentially effective in mitigating loss of muscle mass both
      during and after RT. Future trials should assess the feasibility and effects of
      extended interventions during and after treatment. Cancer 2017;123:4440-8. (c)
      2017 American Cancer Society.

PMID- 28759114
TI  - Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) in pediatric and young adult
      patients: Results from a prospective study using limited-margin radiotherapy.
AB  - BACKGROUND: Indications for and delivery of adjuvant therapies for pediatric
      nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from
      adult studies; therefore, significant concern remains regarding radiation
      exposure to normal tissue. The authors report long-term treatment outcomes and
      toxicities for pediatric and young adult patients with high-grade NRSTS who were
      treated on a prospective trial using limited-margin radiotherapy. METHODS: Sixty
      two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring
      radiation were treated on a phase 2 institutional study of conformal external
      beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically
      constrained margin. The estimated cumulative incidence of local failure, Gray's
      method estimated cumulative incidence of local failure, Kaplan-Meier method
      estimated survival, competing-risk regression model determined predictors of
      disease outcome, and toxicity was reported according to CTCAE v2.0. RESULTS: At a
      median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced
      local failure. The 5-year overall cumulative incidence of local failure was 14.8%
      (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred
      outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates
      for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9%
      (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that
      younger age was the only independent predictor of local recurrence (P = .004).
      The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI,
      7.2%-25.3%). CONCLUSIONS: The delivery of limited-margin radiotherapy using
      conformal external-beam radiotherapy or brachytherapy provides a high rate of
      local tumor control without an increase in marginal failures and with acceptable
      treatment-related morbidity. Cancer 2017;123:4419-29. (c) 2017 American Cancer
      Society.

PMID- 28759115
TI  - Anti-MUC1 aptamer: A potential opportunity for cancer treatment.
AB  - Mucin 1 (MUC1) is a protein usually found on the apical surface of most normal
      secretory epithelial cells. However, in most adenocarcinomas, MUC1 is
      overexpressed, so that it not only appears over the entire cell surface, but is
      also shed as MUC1 fragments into the blood stream. These phenomena pinpoint MUC1
      as a potential target for the diagnosis and treatment of cancer; consequently,
      interest has increased in MUC1 as a molecular target for overcoming cancer
      therapy challenges. MUC1 currently ranks second among 75 antigen candidates for
      cancer vaccines, and different antibodies or aptamers against MUC1 protein are
      proving useful for tracing cancer cells in the emerging field of targeted
      delivery. The unique properties of MUC1 aptamers as novel targeting agents, and
      the revolutionary role that MUC1 now plays in cancer therapy, are the focus of
      this review. Recent advancements in MUC1-targeted cancer therapy are also
      assessed.

PMID- 28759116
TI  - Anterior vaginal repair for urinary incontinence in women.
AB  - BACKGROUND: Anterior vaginal repair (anterior colporrhaphy) is an operation
      traditionally used for moderate or severe stress urinary incontinence (SUI) in
      women. About a third of adult women experience urinary incontinence. SUI imposes
      significant health and economic burden to the society and the women affected.
      OBJECTIVES: To determine the effects of anterior vaginal repair (anterior
      colporrhaphy) on urinary incontinence in comparison with other management
      options. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised
      Trials Register (searched 1 September 2009) and the reference lists of relevant
      articles. SELECTION CRITERIA: Randomised or quasi-randomised trials that included
      anterior vaginal repair for the treatment of urinary incontinence. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted data and
      assessed trial quality. Three trial investigators were contacted for additional
      information. MAIN RESULTS: Ten trials were identified which included 385 women
      having an anterior vaginal repair and 627 who received comparison interventions.A
      single small trial provided insufficient evidence to assess anterior vaginal
      repair in comparison with physical therapy. The performance of anterior repair in
      comparison with bladder neck needle suspension appeared similar (risk ratio (RR)
      for failure after one year 1.16, 95% confidence interval (CI) 0.86 to 1.56), but
      clinically important differences could not be confidently ruled out. No trials
      compared anterior repair with suburethral sling operations or laparoscopic
      colposuspensions, or compared alternative vaginal operations.Anterior vaginal
      repair was less effective than open abdominal retropubic suspension based on
      patient-reported cure rates in eight trials both in the medium term (failure rate
      within one to five years after anterior repair 97/259 (38%) versus 57/327 (17%);
      RR 2.29, 95% confidence Interval (CI) 1.70 to 3.08) and in the long term (after
      five years, (49/128 (38%) versus 31/145 (21%); RR 2.02, 95% CI 1.36 to 3.01).
      There was evidence from three of these trials that this was reflected in a need
      for more repeat operations for incontinence (25/107 (23%) versus 4/164 (2%); RR
      8.87, 95% CI 3.28 to 23.94). These findings held, irrespective of the co
      existence of prolapse (pelvic relaxation). Although fewer women had a prolapse
      after anterior repair (RR 0.24, 95% CI 0.12 to 0.47), later prolapse operation
      appeared to be equally common after vaginal (3%) or abdominal (4%) operation.In
      respect of the type of open abdominal retropubic suspension, most data related to
      comparisons of anterior vaginal repair with Burch colposuspension. The few data
      describing comparison of anterior repair with the Marshall-Marchetti-Krantz
      procedure were consistent with those for Burch colposuspension. AUTHORS'
      CONCLUSIONS: There were not enough data to allow comparison of anterior vaginal
      repair with physical therapy or needle suspension for primary urinary stress
      incontinence in women. Open abdominal retropubic suspension appeared to be better
      than anterior vaginal repair judged on subjective cure rates in eight trials,
      even in women who had prolapse in addition to stress incontinence (six trials).
      The need for repeat incontinence surgery was also less after the abdominal
      operation. However, there was not enough information about postoperative
      complications and morbidity.A Brief Economic Commentary (BEC) identified one
      study suggesting that vaginoplasty may be more cost-effective compared with
      tension-free vaginal tape (TVT-O).

PMID- 28759117
TI  - Fertility options in transgender and gender diverse adolescents.

PMID- 28759118
TI  - Mandibular body fracture repair with wire-reinforced interdental composite splint
      in small dogs.
AB  - OBJECTIVE: To report the outcome of mandibular body fractures treated with a wire
      reinforced interdental composite splint (WRICS) in small breed dogs. STUDY
      DESIGN: Retrospective case series. ANIMALS: Client-owned small breed dogs (n =
      24). METHODS: Medical records (1998-2012) of small breed dogs (<10 kg) with
      mandibular body fractures treated by WRICS were reviewed for signalment, history,
      type of fracture, treatment, and clinical and radiological follow-up. The angle
      of the fracture line (ANG) was measured on dental radiographs. A mandibular
      injury severity score (MISS) and a dental injury score (DIS) were evaluated as
      potential prognostic factors. RESULTS: Fractures most commonly involved P4-M1
      (56%), and healed in a mean time of 2.37 +/- 0.7 months. Healing was slower (P =
      .012) if teeth were present in the fracture line and required extraction,
      hemisection, or root canal therapy prior to WRICS placement (2.39 +/- 0.7 months)
      than if no dental treatment was required (1.46 +/- 0.8 months). Contrary to the
      MISS, the DIS was associated with longer time to bone healing (P = .001; r = .63)
      and risk of complications (P = .004). Bone healing time was decreased (P = .003;
      r = .61) with increasing fracture angles. CONCLUSION: WRICS can be considered to
      treat mandibular body fractures in small breed dogs if the fracture is not
      severely comminuted, and if at least the canine and first molar tooth can be used
      for anchorage. More severe lesions, such as those with teeth in the fracture line
      and a shorter fracture surface, are associated with prolonged bone healing.

PMID- 28759119
TI  - Comparison of design features and mechanical properties of commercially available
      Veress needles.
AB  - OBJECTIVE: To compare design features and mechanical properties of 13
      commercially available Veress needles (VN). STUDY DESIGN: In vitro biomechanical
      study. SAMPLE POPULATION: Veress needles from 9 manufacturers (6 reusable, 6
      disposable, and 1 with a reusable stylet combined with a disposable cannula) were
      included in the study. METHODS: Veress needles are designed with a spring-loaded
      stylet to protect the tip of the cannula following insertion into the abdomen.
      Stylet forces were measured with a scale in a test jig by moving the stylet in
      0.5 mm steps into the hollow cannula. Forces and spring rates were derived from
      force-displacement plots. Mass, mechanical dimensions, and the bevel angle and
      geometry were assessed. Differences between VN models were analyzed with a
      univariate analysis of variance. Results are reported as mean +/- SD or median
      (range). RESULTS: Physical and mechanical parameters differed between models. The
      exposed stylet length was 3.5 mm (2-7). Three bevel geometries (bias, lancet
      type, and back-cut) with angles between 20 degrees  and 40 degrees  were
      identified. Reusable VN weigh more (24.9 +/- 2.2 g) than disposable designs (6.0
      +/- 2.3 g). The mean values for the spring rate and the residual stylet force
      were 0.23 +/- 0.08 Nmm-1 and 0.94 +/- 0.28 N, respectively. The mean force
      required to move the stylet to the cannula tip was 1.81 +/- 0.29 N and 2.77 +/-
      0.54 N to move to the proximal end of the bevel. CONCLUSION: Commercially
      available VN use diverse bevel geometries and have different mechanical
      characteristics. Studies investigating laparoscopic entry complications should
      explicitly report the type of VN model used.

PMID- 28759120
TI  - Pit and fissure sealants for preventing dental decay in permanent teeth.
AB  - BACKGROUND: Dental sealants were introduced in the 1960s to help prevent dental
      caries, mainly in the pits and fissures of occlusal tooth surfaces. Sealants act
      to prevent bacteria growth that can lead to dental decay. Evidence suggests that
      fissure sealants are effective in preventing caries in children and adolescents
      compared to no sealants. Effectiveness may, however, be related to caries
      incidence level of the population. This is an update of a review published in
      2004, 2008 and 2013. OBJECTIVES: To compare the effects of different types of
      fissure sealants in preventing caries in occlusal surfaces of permanent teeth in
      children and adolescents. SEARCH METHODS: Cochrane Oral Health's Information
      Specialist searched: Cochrane Oral Health's Trials Register (to 3 August 2016),
      the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane
      Library, 2016, Issue 7), MEDLINE Ovid (1946 to 3 August 2016), and Embase Ovid
      (1980 to 3 August 2016). We searched ClinicalTrials.gov and the World Health
      Organization International Clinical Trials Registry Platform for ongoing trials
      to 3 August 2016. No restrictions were placed on language or date of publication.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing sealants with
      no sealant or a different type of sealant material for preventing caries of
      occlusal surfaces of premolar or molar teeth in children and adolescents aged up
      to 20 years. Studies required at least 12 months follow-up. We excluded studies
      that compared compomers to resins/composites. DATA COLLECTION AND ANALYSIS: Two
      review authors independently screened search results, extracted data and assessed
      risk of bias of included studies. We presented outcomes for caries or no caries
      on occlusal surfaces of permanent molar teeth as odds ratio (OR) or risk ratio
      (RR). We used mean difference (MD) for mean caries increment. All measures were
      presented with 95% confidence intervals (CI). We conducted meta-analyses using a
      random-effects model for comparisons where there were more than three trials;
      otherwise we used the fixed-effect model. We used GRADE methods to assess
      evidence quality. MAIN RESULTS: We included 38 trials that involved a total of
      7924 children; seven trials were new for this update (1693 participants). Fifteen
      trials evaluated the effects of resin-based sealant versus no sealant (3620
      participants in 14 studies plus 575 tooth pairs in one study); three trials with
      evaluated glass ionomer sealant versus no sealant (905 participants); and 24
      trials evaluated one type of sealant versus another (4146 participants). Children
      were aged from 5 to 16 years. Trials rarely reported background exposure to
      fluoride of trial participants or baseline caries prevalence. Resin-based sealant
      versus no sealant: second-, third- and fourth-generation resin-based sealants
      prevented caries in first permanent molars in children aged 5 to 10 years (at 24
      months follow-up: OR 0.12, 95% CI 0.08 to 0.19, 7 trials (5 published in the
      1970s; 2 in the 2010s), 1548 children randomised, 1322 children evaluated;
      moderate-quality evidence). If we were to assume that 16% of the control tooth
      surfaces were decayed during 24 months of follow-up (160 carious teeth per 1000),
      then applying a resin-based sealant would reduce the proportion of carious
      surfaces to 5.2% (95% CI 3.13% to 7.37%). Similarly, assuming that 40% of control
      tooth surfaces were decayed (400 carious teeth per 1000), then applying a resin
      based sealant would reduce the proportion of carious surfaces to 6.25% (95% CI
      3.84% to 9.63%). If 70% of control tooth surfaces were decayed, there would be
      19% decayed surfaces in the sealant group (95% CI 12.3% to 27.2%). This caries
      preventive effect was maintained at longer follow-up but evidence quality and
      quantity was reduced (e.g. at 48 to 54 months of follow-up: OR 0.21, 95% CI 0.16
      to 0.28, 4 trials, 482 children evaluated; RR 0.24, 95% CI 0.12 to 0.45, 203
      children evaluated). Although studies were generally well conducted, we assessed
      blinding of outcome assessment for caries at high risk of bias for all trials
      (blinding of outcome assessment is not possible in sealant studies because
      outcome assessors can see and identify sealant). Glass ionomer sealant versus no
      sealant: was evaluated by three studies. Results at 24 months were inconclusive
      (very low-quality evidence). One sealant versus another sealant: the relative
      effectiveness of different types of sealants is unknown (very low-quality
      evidence). We included 24 trials that directly compared two different sealant
      materials. Comparisons varied in terms of types of sealant assessed, outcome
      measures chosen and duration of follow-up. Adverse events: only four trials
      assessed adverse events. No adverse events were reported. AUTHORS' CONCLUSIONS:
      Resin-based sealants applied on occlusal surfaces of permanent molars are
      effective for preventing caries in children and adolescents. Our review found
      moderate-quality evidence that resin-based sealants reduced caries by between 11%
      and 51% compared to no sealant, when measured at 24 months. Similar benefit was
      seen at timepoints up to 48 months; after longer follow-up, the quantity and
      quality of evidence was reduced. There was insufficient evidence to judge the
      effectiveness of glass ionomer sealant or the relative effectiveness of different
      types of sealants. Information on adverse effects was limited but none occurred
      where this was reported. Further research with long follow-up is needed.

PMID- 28759121
TI  - Health care disparities among octogenarians and nonagenarians with stage II and
      III rectal cancer.
AB  - BACKGROUND: Octogenarians and nonagenarians with stage II/III rectal
      adenocarcinomas are underrepresented in the randomized trials that have
      established the standard-of-care therapy of preoperative chemoradiation followed
      by definitive resection (ie, chemoradiation and then surgery [CRT+S]). The
      purpose of this study was to evaluate the impact of therapies on overall survival
      (OS) for patients with stage II/III rectal cancers and determine predictors of
      therapy within the National Cancer Data Base (NCDB). METHODS: In the NCDB,
      patients who were 80 years old or older and had clinical stage II/III rectal
      adenocarcinoma from 2004 to 2013 were queried. Kaplan-Meier analysis, log-rank
      testing, logistic regression, Cox proportional hazards regression, interaction
      effect testing, and propensity score-matched analysis were conducted. RESULTS:
      The criteria were met by 2723 patients: 14.9% received no treatment, 29.7% had
      surgery alone, 5.0% underwent short-course radiation and then surgery (RT+S),
      45.3% underwent CRT+S, and 5.1% underwent surgery and then chemoradiation
      (S+CRT). African American race and residence in a less educated county were
      associated with not receiving treatment. Male sex, older age, worsening
      comorbidities, and receiving no treatment or undergoing surgery alone were
      associated with worse OS. There was no statistical difference in OS between RT+S,
      S+CRT, and CRT+S. Interaction testing found that CRT+S improved OS independently
      of age, comorbidity status, sex, race, and tumor stage. In the propensity score
      matched analysis, CRT+S was associated with improved OS in comparison with
      surgery alone. CONCLUSIONS: A significant portion of octogenarians and
      nonagenarians with stage II/III rectal adenocarcinomas do not receive treatment.
      African American race and living in a less educated community are associated with
      not receiving therapy. This series suggests that CRT+S is a reasonable strategy
      for elderly patients who can tolerate therapy. Cancer 2017;123:4325-36. (c) 2017
      American Cancer Society.

PMID- 28759123
TI  - Detecting population-environmental interactions with mismatched time series data.
AB  - Time series analysis is an essential method for decomposing the influences of
      density and exogenous factors such as weather and climate on population
      regulation. However, there has been little work focused on understanding how well
      commonly collected data can reconstruct the effects of environmental factors on
      population dynamics. We show that, analogous to similar scale issues in spatial
      data analysis, coarsely sampled temporal data can fail to detect covariate
      effects when interactions occur on timescales that are fast relative to the
      survey period. We propose a method for modeling mismatched time series data that
      couples high-resolution environmental data to low-resolution abundance data. We
      illustrate our approach with simulations and by applying it to Florida's southern
      Snail kite population. Our simulation results show that our method can reliably
      detect linear environmental effects and that detecting nonlinear effects requires
      high-resolution covariate data even when the population turnover rate is slow. In
      the Snail kite analysis, our approach performed among the best in a suite of
      previously used environmental covariates explaining Snail kite dynamics and was
      able to detect a potential phenological shift in the environmental dependence of
      Snail kites. Our work provides a statistical framework for reliably detecting
      population-environment interactions from coarsely surveyed time series. An
      important implication of this work is that the low predictability of animal
      population growth by weather variables found in previous studies may be due, in
      part, to how these data are utilized as covariates.

PMID- 28759122
TI  - Differential effects of late gestation maternal overnutrition on the regulation
      of surfactant maturation in fetal and postnatal life.
AB  - KEY POINTS: Offspring of overweight and obese women are at greater risk for
      respiratory complications at birth. We determined the effect of late gestation
      maternal overnutrition (LGON) in sheep on surfactant maturation, glucose
      transport and fatty acid metabolism in the lung in fetal and postnatal life.
      There were significant decreases in surfactant components and numerical density
      of surfactant producing cells in the alveolar epithelium due to LGON in the fetal
      lung. However, there were no differences in the levels of these surfactant
      components between control and LGON lambs at 30 days of age. The reduced capacity
      for surfactant production in fetuses as a result of LGON may affect the
      transition to air breathing at birth. There was altered glucose transport and
      fatty acid metabolism in the lung as a result of LGON in postnatal life. However,
      there is a normalisation of surfactant components that suggests accelerated
      maturation in the lungs after birth. ABSTRACT: With the increasing incidence of
      obesity worldwide, the proportion of women entering pregnancy overweight or obese
      has increased dramatically. The fetus of an overnourished mother experiences
      numerous metabolic changes that may modulate lung development and hence
      successful transition to air breathing at birth. We used a sheep model of
      maternal late gestation overnutrition (LGON; from 115 days' gestation, term 147
      +/- 3 days) to determine the effect of exposure to an increased plane of
      nutrition in late gestation on lung development in the fetus (at 141 days'
      gestation) and the lamb (30 days after birth). We found a decrease in the
      numerical density of surfactant protein positive cells, as well as a reduction in
      mRNA expression of surfactant proteins (SFTP-A, -B and -C), a rate limiting
      enzyme in surfactant phospholipid synthesis (phosphate cytidylyltransferase 1,
      choline, alpha; PCYT1A), and glucose transporters (SLC2A1 and SLC2A4) in the
      fetal lung. In lambs at 30 days after birth, there were no differences between
      Control and LGON groups in the surfactant components that were downregulated in
      the LGON fetuses. However, mRNA expression of SFTP-A, PCYT1A, peroxisome
      proliferator activated receptor-gamma, fatty acid synthase and fatty acid
      transport protein were increased in LGON lambs compared to controls. These
      results indicate a reduced capacity for surfactant production in late gestation.
      While these deficits are normalised by 30 days after birth, the lungs of LGON
      lambs exhibited altered glucose transport and fatty acid metabolism, which is
      consistent with an enhanced capacity for surfactant synthesis and restoration of
      surfactant maturity in these animals.

PMID- 28759124
TI  - Recent advances in uveal melanoma treatment.
AB  - Uveal melanoma (UM) is the most common primary intraocular malignancy in adults.
      Recent advances in the understanding of molecular characteristics helped to
      determine which tumors are most likely to progress. About 50% of patients
      carrying genetic alterations such as chromosomal aberrations and mutations are at
      significant risk for metastatic disease of which the majority will succumb to UM
      within few months. Currently, there is no effective treatment for metastatic
      uveal melanoma, and we hope this review will encourage researchers and clinicians
      to work to find a better standard of care. In this article we provide a
      comprehensive overview of the molecular framework of UM, highlighting the most
      common mutations involved in this kind of cancer. It also covers the most recent
      treatments from basic research to clinical trials, including small molecules,
      nucleic acids or immunotherapy, among others. It is intended to serve as a key
      reference for clinicians and researchers working in this field.

PMID- 28759125
TI  - Thrombopoietin receptor agonist switch in adult primary immune thrombocytopenia
      patients: A retrospective collaborative survey involving 4 Spanish centres.
AB  - OBJECTIVE: To describe the reasons for and result of thrombopoietin receptor
      agonists (TPO-RA) switching in adult immune thrombocytopenia (ITP) patients of 4
      Spanish centres. METHODS: We retrospectively analysed all patients who received
      sequential treatment with both TPO-RA between 2010 and 2015 recording clinical
      and biological parameters. RESULTS: Twenty-six patients were included; 17
      received first romiplostim and 9 received first eltrombopag. Reasons for
      switching were inefficacy (n = 10), patient preference (n = 8), side effects (n =
      5) and excessive platelet count fluctuation (n = 3). When the switch was due to
      inefficacy, 100% of patients who received romiplostim first and 66% who received
      eltrombopag first responded to the second drug. It is significant that none of
      the patients who received romiplostim first reached the maximum recommended dose
      before switching. When the change was due to patient preference or because of
      side effects, 100% of the patients responded to both TPO-RA. Three patients
      changed from romiplostim to eltrombopag due to platelet count fluctuation; one
      did not respond and the fluctuation persisted in the remaining 2 patients. We
      also found 4 sustained remissions after administering the second TPO-RA, 2 of
      these with inefficacy of the first drug. CONCLUSION: TPO-RA switching is a
      feasible strategy in different scenarios with high probability of success.

PMID- 28759126
TI  - EP2 receptor plays pivotal roles in generating mechanical hyperalgesia after
      lengthening contractions.
AB  - We previously demonstrated that nerve growth factor (NGF) and glial cell line
      derived neurotrophic factor (GDNF) were upregulated after lengthening
      contractions (LC) in exercised muscle through B2 bradykinin receptor activation
      and cyclooxygenase (COX)-2 upregulation, respectively, and that these trophic
      factors sensitized nociceptors resulting in mechanical hyperalgesia (delayed
      onset muscle soreness, DOMS). Here, we examined the prostaglandin receptor
      subtype involved in DOMS. The mechanical withdrawal threshold of the exercised
      muscle was measured before and after LC in rats administered prostaglandin E2
      receptor (EP) antagonists before LC, or in wild-type (WT), EP2 knockout (EP2-/-
      ), and IP knockout (IP-/- ) mice. The change in expression of NGF, GDNF, or COX-2
      mRNA was examined using real-time RT-PCR in the muscle in EP2-/- and WT mice.
      None of the antagonists to EP1, EP3, and EP4 receptors (ONO-8713, ONO-AE5-599,
      and ONO-AE3-208, respectively) induced a significant difference in DOMS compared
      with controls in rats. WT and IP-/- mice developed mechanical hyperalgesia after
      LC, but EP2-/- mice did not. Upregulation of NGF, GDNF, and COX-2 mRNA was
      observed after LC in WT mice but not in EP2-/- mice. Injecting an EP2 agonist
      (ONO-AE1-259-01) into the mouse muscle increased expression of COX-2 mRNA. These
      results suggest that EP2 contributes to generating mechanical hyperalgesia
      through positive feedback upregulation of COX-2 expression in muscle after LC.

PMID- 28759127
TI  - Kinematic stride cycle asymmetry is not associated with sprint performance and
      injury prevalence in athletic sprinters.
AB  - The aims of this study were to (a) quantify the magnitude of kinematic stride
      cycle asymmetry in high-level athletic sprinters, (b) explore the association
      between kinematic asymmetry and maximal sprint running performance, and (c)
      investigate possible associations between kinematic asymmetry and injury
      prevalence. Twenty-two competitive sprinters (age 23 +/- 3 year, height 1.81 +/-
      0.06 m, body mass 75.5 +/- 5.6 kg, personal best 100 m 10.86 +/- 0.22 seconds)
      performed 2-3 flying sprints over 20 m. Kinematics were recorded in 3D using a
      motion tracking system with 21 cameras at a 250 Hz sampling rate, allowing
      assessment of six consecutive steps for each athlete. Information about injuries
      sustained 1 year prior to and after the experiment was continuously registered
      (type, location, severity/duration, and time of year occurrence). The results
      showed that >=11 of the 22 participating athletes displayed large or very large
      asymmetry for at least 11 of 14 variables, and all athletes displayed large or
      very large asymmetry for at least three variables. No correlations between
      individual magnitudes of asymmetry and sprint performance were significant
      (trivial to moderate). No significant changes in asymmetry between best and worst
      trial were observed for any of the analyzed variables. In addition, injured and
      non-injured athletes did not differ in asymmetry, neither for the time period 1
      year prior to nor after the test. In conclusion, kinematic asymmetries in the
      stride cycle were not associated with neither maximal sprint running performance
      nor the prevalence of injury among high-level athletic sprinters.

PMID- 28759128
TI  - From Square-Planar [ICl4 ]- to Novel Chloroiodates(III)? A Systematic
      Experimental and Theoretical Investigation of Their Ionic Liquids.
AB  - A systematic investigation on the existence of chloroiodates formed by reaction
      of Cl- with I2 Cl6 , apart from the well-known [ICl4 ]- , namely [I2 Cl7 ]- and
      [I3 Cl10 ]- , was undertaken by employing theoretical as well as experimental
      methods. The thermodynamic stability in terms of the complexation enthalpies and
      Gibbs energies, and also the decomposition of the iodine(III) polyinterhalogen
      anions through dichlorine elimination to form iodine (I) compounds, was studied
      by means of DFT and ab initio quantum-chemical calculations up to an extrapolated
      CCSD(T)/A'QZ level. On the experimental side, mixtures of [HMIM]Cl ([HMIM]+ =1
      hexyl-3-methylimidazolium), [BMP]Cl ([BMP]+ =1-butyl-1-methylpyrrolidinium
      chloride) and [NEt4 ]Cl with 0.5, 1.0, and 1.5 equivalents of I2 Cl6 were
      investigated by single-crystal XRD, ion chromatography, NMR- and Raman
      spectroscopy. The reactions with 0.5 equivalents of I2 Cl6 resulted in the
      compounds [HMIM][ICl4 ], [BMP][ICl4 ], and [NEt4 ][ICl4 ], of which crystal
      structures were determined. The mixtures with 1.0 or 1.5 equivalents of I2 Cl6
      yielded dark red liquids or suspensions of a dark red liquid with an orange
      solid, respectively. Both mixtures were studied by NMR-spectroscopy for the
      organic cation part and ion chromatography and Raman spectroscopy for the
      polyinterhalogen anions. The discussion of the experimental Raman spectra is
      supplemented with computed spectra based on the structures obtained from RI
      MP2/def2-TZVPP structure optimisations. Overall [I2 Cl7 ]- appears to be the
      predominating anionic species in mixtures with 1.0 equivalents I2 Cl6 , while
      mixtures with 1.5 equivalents of I2 Cl6 are suspensions of I2 Cl6 in a liquid
      phase containing mixed anionic interhalogen complexes.

PMID- 28759129
TI  - The effect of a two-year school-based daily physical activity intervention on a
      clustered CVD risk factor score-The Sogndal school-intervention study.
AB  - To evaluate changes in clustered cardiovascular disease (CVD) risk factors in 9
      year-old children following a 2-year school-based physical activity intervention.
      In total, 259 children (age 9.3 +/- 0.3 years) were invited, of whom 256
      participated. The intervention group (63 boys, 62 girls) carried out 60-minute
      teacher-controlled daily physical activity over two school years. The control
      group (62 boys, 69 girls) had the curriculum-defined amount of physical education
      (45 minutes twice each week). Of these, 67% (171 total, 91 intervention)
      successfully completed both baseline and post-intervention of six CVD risk
      factors: systolic blood pressure (SBP), triglyceride (TG), total cholesterol-to
      high-density lipoprotein cholesterol ratio (TC:HDL ratio), waist circumference
      (WC), the homeostasis model assessment for insulin resistance (HOMA), and peak
      oxygen uptake (VO2peak ). All variables were standardized by sex prior to
      constructing a cluster score (sum of z scores for all variables). The effect of
      the intervention on the cluster score was analyzed using linear multiple
      regression. The cluster score improved after the intervention (ES = .29).
      Furthermore, the analyses showed significant effects in favor of the intervention
      group for systolic blood pressure (ES = .35), total cholesterol-to-HDL-c ratio
      (ES = .23), triglyceride (ES = .40), and VO2peak (ES = .57). A teacher-led school
      based physical activity intervention that is sufficiently long and includes a
      substantial amount of daily physical activity can beneficially modify children's
      clustered CVD risk profile.

PMID- 28759130
TI  - The joint impact of prediagnostic inflammatory markers and cardiorespiratory
      fitness on the risk of cancer mortality.
AB  - Independently, cardiorespiratory fitness (CRF), C-reactive protein (CRP), and
      leukocyte count have been shown to predict cancer death. Little is known about
      the joint impact of CRF and prediagnostic markers of inflammation, particularly
      leukocyte count and CRP, and their prognostic value with cancer death. The aim of
      this study was to explore the association between prediagnostic inflammatory
      markers and CRF with cancer mortality. A population-based cohort of 2270 men from
      Eastern Finland with no cancer history at baseline participated in the study.
      CRP, leukocyte count, and CRF data were among the measures collected at baseline.
      Blood leukocyte count was measured with a cell counter, and serum CRP
      concentrations were measured using an immunometric assay. The highest value or
      plateau of directly measured oxygen consumption by a respiratory gas analyzer
      during an incremental exercise test to exhaustion was used to describe CRF. Over
      an average follow-up of 22 years, 272 cases of cancer mortality occurred. In a
      multivariate model, the joint impact of high leukocyte count (>5.40 * 109 /L) and
      low CRF (VO2 max < 30.08 mL kg-1  min-1 ) had a 1.85-fold (95% CI 1.30-2.63, P <
      .01) increased risk for cancer death compared to men with low leukocyte count
      (<5.40 * 109 /L) and high CRF (VO2 max > 30.08 mL kg-1  min-1 ). The joint impact
      of CRP and CRF shared no association with cancer mortality in a multivariate
      model. The joint impact of high leukocyte count and low CRF increases risk for
      cancer death, suggesting it is a better predictor of cancer death compared to the
      joint impact of CRP and CRF.

PMID- 28759132
TI  - Is early postnatal growth velocity, a proxy of minipubertal androgen action,
      related to adult second-to-fourth digit (2D:4D) ratios in men? A test in Cebu,
      Philippines.
AB  - OBJECTIVES: The ratio of the length of the second to the fourth digit (2D:4D) of
      the hand is often used as an index of prenatal androgen exposure but it might
      also be affected by androgens during "minipuberty," a period of temporarily high
      testosterone (T) production in the first few months of life. To examine this, we
      tested the prediction that men with lower 2D:4D ratios had greater weight growth
      velocities during the first months of life-a metric recently shown to correlate
      with concurrent T levels. METHODS: We related early growth data to 2D:4D ratios
      of both hands measured in 756 men (25-26 years) from Cebu, The Philippines.
      RESULTS: Birth-to-fourth-month (B4M) weight gain velocity (a proxy of early
      postnatal androgen action) was not associated with adult 2D:4D ratios of either
      hand, when the latter was measured continuously. When comparing men with more
      male-typical digit ratios (<1.0) to those with more female-typical ratios (>=
      1.0), the group of men with more male-typical ratios had greater B4M weight
      velocity, but this was only the case for the left hand. CONCLUSIONS: We found
      modest evidence that adult digit ratios relate to an anthropometric correlate of
      androgen exposure during minipuberty. Definitive assessment of the role of
      postnatal T in shaping digit ratios will require direct measures of perinatal T
      related to longitudinally assessed digit ratios.

PMID- 28759131
TI  - Neuromuscular adaptability of male and female rats to muscle unloading.
AB  - Previously, it has been shown that following muscle unloading, males and females
      experience different maladaptations in neuromuscular function. As a follow-up,
      the present investigation sought to determine if male and female neuromuscular
      systems demonstrated similar, or disparate morphological adaptations to muscle
      unloading. Twenty young adult male, and 20 young adult female rats were randomly
      assigned to one of two treatment protocols: muscle unloading, or control
      conditions. Following the 2-week intervention period, immunofluorescent
      procedures were used to quantify pre- and post-synaptic features of neuromuscular
      junctions (NMJs), and to assess myofiber profiles (size and fiber type
      composition) of the soleus, plantaris, and EDL muscles. A 2-way ANOVA with main
      effects for sex and treatment was then used to identify statistically significant
      (p <= .05) differences among structural parameters. Analysis of NMJs showed a
      consistent lack of differences between males and females. Overall, NMJs were also
      found to be resistant to the effects of unloading. When examining myofiber
      profiles, however, male myofibers were revealed to be significantly larger than
      female ones in each of the muscles examined. Unloading resulted in significant
      myofiber atrophy only in the primarily weight-bearing soleus muscle. Only the EDL
      showed unloading-induced differences in myofiber type distribution (Type II ->
      I). These data indicate that different components of the neuromuscular system
      (NMJs, myofibers) respond uniquely to unloading, and that sex affects myofiber
      type profiles, but not NMJs. Moreover, it appears that only muscles that have
      their habitual activity patterns disturbed by unloading (i.e., the soleus, adapt
      to that intervention).

PMID- 28759133
TI  - A Four-Armed Unsymmetrical Cryptand: From Two Different Host-Guest Interactions
      to Responsive Supramolecular Polymer.
AB  - By linking BMP32C10 and DB24C8 motifs together, a four-armed cryptand 1 is
      synthesized successfully, in which BMP32C10 motif can bind paraquat 2 while
      DB24C8 motif can complex dibenzylammonium salt 3 in spite of the electrostatic
      repulsion between guests 2 and 3. The base/acid-responsive supramolecular polymer
      is constructed further via two kinds of host-guest interactions between cryptand
      1 and two homoditopic paraquat 4 and dibenzylammonium salt 5 similar to guests 2
      and 3.

PMID- 28759134
TI  - Self-Assembled Luminescent Quantum Dots To Generate Full-Color and White
      Circularly Polarized Light.
AB  - The design and fabrication of quantum dots (QDs) with circularly polarized
      luminescence (CPL) has been a great challenge in developing chiroptical
      materials. We herein propose an alternative to the use of chiral capping reagents
      on QDs for the fabrication of CPL-active QDs that is based on the supramolecular
      self-assembly of achiral QDs with chiral gelators. Full-color-tunable CPL-active
      QDs were obtained by simple mixing or gelation of a chiral gelator and achiral 3
      mercaptopropionic acid capped QDs. In addition, the handedness of the CPL can be
      controlled by the supramolecular chirality of the gels. Moreover, QDs with
      circularly polarized white light emission were fabricated for the first time by
      tuning the blending ratio of colorful QDs in the gel. The chirality transfer in
      the co-assembly of the achiral QDs with the gelator and the spacer effect of the
      capping reagents on the QD surface are also discussed. This work provides new
      insight into the design of functional chiroptical materials.

PMID- 28759135
TI  - Acute and long-term administration of palmitoylcarnitine induces muscle-specific
      insulin resistance in mice.
AB  - Acylcarnitine accumulation has been linked to perturbations in energy metabolism
      pathways. In this study, we demonstrate that long-chain (LC) acylcarnitines are
      active metabolites involved in the regulation of glucose metabolism in vivo.
      Single-dose administration of palmitoylcarnitine (PC) in fed mice induced marked
      insulin insensitivity, decreased glucose uptake in muscles, and elevated blood
      glucose levels. Increase in the content of LC acylcarnitine induced insulin
      resistance by impairing Akt phosphorylation at Ser473. The long-term
      administration of PC using slow-release osmotic minipumps induced marked
      hyperinsulinemia, insulin resistance, and glucose intolerance, suggesting that
      the permanent accumulation of LC acylcarnitines can accelerate the progression of
      insulin resistance. The decrease of acylcarnitine content significantly improved
      glucose tolerance in a mouse model of diet-induced glucose intolerance. In
      conclusion, we show that the physiological increase in content of acylcarnitines
      ensures the transition from a fed to fasted state in order to limit glucose
      metabolism in the fasted state. In the fed state, the inability of insulin to
      inhibit LC acylcarnitine production induces disturbances in glucose uptake and
      metabolism. The reduction of acylcarnitine content could be an effective strategy
      to improve insulin sensitivity. (c) 2017 BioFactors, 43(5):718-730, 2017.

PMID- 28759136
TI  - Extracorporeal shock wave therapy for chronic wounds: A systematic review and
      meta-analysis of randomized controlled trials.
AB  - A growing number of clinical studies demonstrate that extracorporeal shock wave
      therapy (ESWT) is a feasible noninvasive method for improving chronic wound
      healing. This systematic review and meta-analysis aimed to assess the
      effectiveness of ESWT compared with that of the standard care treatment for the
      healing of chronic wounds, irrespective of etiology, in clinical practice.
      Randomized controlled trials that investigated the effect of ESWT on chronic
      wounds with different etiologies from 2000 to 2017 were included in this review.
      The methodological quality of each selected article was rated using the Jadad
      scale. A fixed or random effects model was used to calculate the pooled effect
      sizes according to the heterogeneity of the studies. The cumulative effect of
      ESWT on each outcome was illustrated using forest plots. Seven randomized
      controlled trials involving 301 subjects were included in this review. Meta
      analyses revealed that the use of ESWT as an adjunct to wound treatment could
      significantly accelerate the impaired healing process of chronic wounds. Compared
      with the control treatment, ESWT markedly increased the wound healing rate by
      1.86-fold (OR = 2.86, 95% CI: 1.63-5.03, p = 0.0003) and the percentage of the
      wound healing area by 30.46% (SMD = 30.46; 95% CI: 23.80-37.12; p < 0.00001). In
      addition, the wound healing time was reduced by 19 days (SMD = -19.11, 95% CI: 
      23.74-(-14.47), p < 0.00001) in chronic wound patients. No serious complications
      or adverse effects were observed secondary to the application of ESWT. The above
      data suggested that ESWT as an adjunct to wound treatment, could more
      significantly improve the healing process of chronic wounds than the standard
      care treatment alone. More high-quality, well-controlled randomized trials are
      needed to evaluate the efficacy of ESWT in clinical practice.

PMID- 28759137
TI  - Soft tissue sarcomas: From a morphological to a molecular biological approach.
AB  - Recently developed molecular genetic techniques have led to the elucidation of
      tumor-specific genomic alterations and thereby the reclassification of tumor
      entities of soft tissue sarcoma. A solitary fibrous tumor-mimicking tumor with
      the AHRR-NCOA2 gene has been isolated as angiofibroma of soft tissue. As for
      small round cell sarcomas, novel fusion genes such as CIC-DUX4 and BCOR-CCNB3
      have been identified in these tumor groups. SMARCB1/INI1 deficient tumors with
      round cell morphology are also expected to be reclassified in three types, based
      on the combination of their morphology and genotype. The identification of the
      MDM2 gene amplification in pleomorphic sarcomas has extended the entity of
      dedifferentiated liposarcoma (DDLS). Our recent molecular investigations
      elucidated candidates for novel therapeutic strategies. Activation of the Akt
      mTOR pathway was correlated with poor prognosis or tumor grade in spindle cell
      sarcomas including malignant peripheral nerve sheath tumor. In vitro and in vivo
      studies of transcription factor Forkhead Box M1 (FOXM1) demonstrated the close
      correlation between aggressive biological behavior or chemosensitivity and FOXM1
      expression in synovial sarcoma, so far. Finally, in regard to the investigation
      of cancer-testis antigens, myxoid/round cell liposarcoma and synovial sarcoma
      showed frequent and high expression of PRAME and NY-ESO-1.

PMID- 28759138
TI  - Formation of Binuclear Zigzag Hexapentaene Titanium Complexes via a
      Titanacumulene [Ti=C=C=CH2 ] Intermediate.
AB  - The reaction of bis(eta5 :eta1 -pentafulvene)titanium complexes with an
      allylidenephosphorylide Ph3 P=C(H)- C(H)=CH2 leads to binuclear zigzag
      hexapentaene titanium complexes (Ti2a, Ti2b). The formation of the central C6 H4
      unit can be described as a spontaneous double C-H bond activation process,
      leading to an R3 P=C=C=CH2 intermediate, as a synthon for a titanabutatriene
      fragment [(CpR )2 Ti=C=C=CH2 ] (R: 2-adamantyl, CH(p-tol)2 ). In a subsequent
      dimerization Ti2a and Ti2b are formed, proofed by single-crystal X-ray
      diffraction and NMR measurements. The reaction sequence is confirmed by DFT
      calculations.

PMID- 28759139
TI  - Catalytic Divergent [3+3]- and [3+2]-Cycloaddition by Discrimination Between
      Diazo Compounds.
AB  - Highly selective divergent cycloaddition reactions of enoldiazo compounds and
      alpha-diazocarboximides catalyzed by copper(I) or dirhodium(II) have been
      developed. With tetrakis(acetonitrile)copper(I) tetrafluoroborate as the catalyst
      epoxypyrrolo[1,2-a]azepine derivatives were prepared in good yields and excellent
      diastereoselectivities through the first reported [3+3]-cycloaddition of a
      carbonyl ylide. Use of Rh2 (pfb)4 or Rh2 (esp)2 directs the reactants to
      regioselective [3+2]-cycloaddition generating cyclopenta[2,3]pyrrolo[2,1
      b]oxazoles with good yields and excellent diastereoselectivities.

PMID- 28759140
TI  - Artificial Metallooxidases from Cyclodextrin Diacids.
AB  - Unprecedented simple artificial metalloenzymes were made from cyclodextrin
      diacids. Six alpha- and beta-cyclodextrin diacids were prepared and their metal
      binding and acid properties were investigated. The diacids formed fairly stable
      complexes with copper, zinc, and iron, with dissociation constants of 0.4-8*10-4 
      m. The iron complexes were found to catalyse a Fenton-like oxidation reaction of
      benzylic alcohols, which displayed Michaelis-Menten catalysis and rate
      accelerations up to 2700.

PMID- 28759141
TI  - N-Methyl Inversion and Accurate Equilibrium Structures in Alkaloids:
      Pseudopelletierine.
AB  - A rotational spectroscopy investigation has resolved the conformational
      equilibrium and structural properties of the alkaloid pseudopelletierine. Two
      different conformers, which originate from inversion of the N-methyl group from
      an axial to an equatorial position, have been unambiguously identified in the gas
      phase, and nine independent isotopologues have been recorded by Fourier-transform
      microwave spectroscopy in a jet expansion. Both conformers share a chair-chair
      configuration of the two bridged six-membered rings. The conformational
      equilibrium is displaced towards the axial form, with a relative population in
      the supersonic jet of Naxial /Nequatorial ~2/1. An accurate equilibrium structure
      has been determined by using the semiexperimental mixed-estimation method and
      alternatively computed by quantum-chemical methods up to the coupled-cluster
      level of theory. A comparison with the N-methyl inversion equilibria in related
      tropanes is also presented.

PMID- 28759142
TI  - Luminescent Zinc Fingers: Zn-Responsive Neodymium Near-Infrared Emission in
      Water.
AB  - Responsive luminescent probes emitting in the near-infrared (NIR) are in high
      demand today for biological applications as they allow for the easy and
      unambiguous discrimination of autofluorescence. Due to their luminescence
      properties, lanthanide ions offer an interesting alternative to classical organic
      fluorescent dyes. This has stimulated the development of lanthanide-based
      responsive probes. Nevertheless, responsive probes that can operate in water with
      NIR-emitting lanthanide ions are scarce. In this communication, zinc fingers are
      shown to be versatile scaffolds to elaborate a variety of Zn2+ -responsive probes
      based on lanthanide emission and featuring desirable properties for the selective
      detection of Zn2+ in experimental conditions close to cellular. Of special
      interest is a NIR-emitting probe relying on Nd3+ emission.

PMID- 28759143
TI  - Facile Synthesis of In-Chain, Multicomponent, Functionalized Polymers via Living
      Anionic Copolymerization through the Ugi Four-Component Reaction (Ugi-4CR).
AB  - By combining living anionic polymerization and the highly efficient Ugi four
      component reaction (Ugi-4CR), in-chain, multicomponent, functionalized polymers
      are facilely synthesized with efficient conversation and abundant functionality.
      l-[4-[N,N-Bis(trimethylsilyl)-amino]phenyl]-l-phenylethylene, which is redefined
      as Ugi-DPE, is anionically copolymerized to synthesize the well-defined in-chain,
      multi-amino functionalized polystyrene (P(St/DPE-NH2 )), the backbone for the Ugi
      4CR, via hydrolysis of the copolymerization (P(St/Ugi-DPE)). Subsequently,
      several functionalized components are facilely clicked onto P(St/DPE-NH2 ) to
      investigate the model reactions of the in-chain, multicomponent functionalization
      via the Ugi-4CR. In contrast to conventional postpolymerization modifications,
      this approach proceeds under mild reaction conditions without the use of a
      catalyst and meanwhile an efficient conversation is obtained. Finally, the
      modified experimental results investigated in this research show the promising
      potential of the combination of well-defined amino functionalized polymers and
      Ugi-4CR in the field of multicomponent, functionalized postpolymerization
      modification.

PMID- 28759144
TI  - Multiple Metal-Metal Bond or No Bond? The Electronic Structure of V2 O2.
AB  - Detailed knowledge of the electronic structure of vanadium oxide clusters
      provides the basis for understanding and tuning their significant catalytic
      properties. However, already for the simple four-atom V2 O2 molecule, there are
      contradictory reports in the literature regarding the electronic ground state and
      a possible vanadium-vanadium bond. We herein show through a combination of
      experimental (matrix isolation) studies and theoretical results that there is a
      multiple vanadium-vanadium bond in this benchmark vanadium oxide molecule.

PMID- 28759145
TI  - Taming the High Reactivity of Gold(III) Fluoride: Fluorido Gold(III) Complexes
      with N-Based Ligands.
AB  - The synthesis of [NMe4 ][AuF4 ] and [NEt4 ][AuF4 ], as well as an improved one
      pot synthesis of Cs[AuF4 ], is reported. The new [AuF4 ]- salts were structurally
      characterized by single crystal X-ray diffraction, NMR spectroscopy, vibrational
      spectroscopy, and mass spectrometry. These salts are the first gold(III) fluoride
      salts that can be isolated in pure form and are convenient to be used in usual
      organic solvents for subsequent synthesis. The formation of molecular AuF3
      complexes in solution is further reported, characterized as [F3 Au(NCCH3 )] at
      low temperature, as [F3 Au(py)] and a binuclear derivative which are stable at
      room temperature. The stability of these species in common organic solvents was
      investigated and they showed a satisfying stability.

PMID- 28759146
TI  - Lumacaftor/ivacaftor combination therapy for cystic fibrosis: A nationwide survey
      among clinicians.

PMID- 28759147
TI  - Revisiting Hansen Solubility Parameters by Including Thermodynamics.
AB  - The Hansen solubility parameter approach is revisited by implementing the
      thermodynamics of dissolution and mixing. Hansen's pragmatic approach has earned
      its spurs in predicting solvents for polymer solutions, but for molecular solutes
      improvements are needed. By going into the details of entropy and enthalpy,
      several corrections are suggested that make the methodology thermodynamically
      sound without losing its ease of use. The most important corrections include
      accounting for the solvent molecules' size, the destruction of the solid's
      crystal structure, and the specificity of hydrogen-bonding interactions, as well
      as opportunities to predict the solubility at extrapolated temperatures. Testing
      the original and the improved methods on a large industrial dataset including
      solvent blends, fit qualities improved from 0.89 to 0.97 and the percentage of
      correct predictions rose from 54 % to 78 %. Full Matlab scripts are included in
      the Supporting Information, allowing readers to implement these improvements on
      their own datasets.

PMID- 28759148
TI  - Efficacy of prednisone for prevention of esophageal stricture after endoscopic
      submucosal dissection for superficial esophageal squamous cell carcinoma.
AB  - BACKGROUND: Our objective was to investigate the efficacy and safety of oral
      prednisone for the prevention of esophageal stricture formation after endoscopic
      submucosal dissection (ESD) in an optimal administration program. METHODS:
      Patients who underwent circumferential or semi-circumferential (more than three
      quarters but not a complete circular) ESD for esophageal squamous cell carcinoma
      were eligible for this study. Oral prednisolone was administered to the study
      group at a dose of 30 mg/day on the third day post-ESD, and then tapered
      gradually (30, 25, 20, 15, 10, and 5 mg for 14 days). Serial esophagoscopy with
      iodine staining was performed to assess stenosis and tumor recurrence at one,
      three, six, and 12 months after ESD. Endoscopic balloon dilatation was performed
      whenever patients experienced persistent dysphagia to solids. Data were
      statistically analyzed. RESULTS: Twenty-three patients (15 men, mean age 66.6
      years) were enrolled in the study. Post-procedural esophageal stricture was
      significantly lower in the study group (23.1%) compared to the control (80%) (P <
      0.05). A significantly higher number of endoscopic balloon dilatation sessions
      were performed (P < 0.05) in the control (13.5) than in the study group (0.69).
      There were no adverse events related to oral prednisolone or the procedure itself
      and no treatment-related mortality was observed during the 12 month follow-up.
      CONCLUSIONS: Our study suggested an optimal administration program of oral
      prednisone therapy and demonstrated that it is safe and effective for the
      prevention of esophageal stricture in patients after complete or semi-circular
      ESD for esophageal squamous cell carcinoma.

PMID- 28759149
TI  - Simultaneous determination of simazine, cyanazine, and atrazine in honey samples
      by dispersive liquid-liquid microextraction combined with high-performance liquid
      chromatography.
AB  - A rapid and simple sample preparation method was developed for simultaneous
      determination of three triazine herbicides in honey samples. The selected
      herbicides were extracted from honey samples by ionic liquid dispersive liquid
      liquid microextraction, separated on a C18 column (250 mm * 4.6 mm id, 5 MUm)
      using acetonitrile and H2 O as the mobile phase with gradient elution, and then
      detected by high-performance liquid chromatography. The parameters, such as the
      type and volume of the extraction and disperser solvent, ion strength, pH,
      extraction time, and centrifuge time were optimized in order to provide the
      excellent extraction performance. Good linearity was showed for all the target
      herbicides over the tested concentration range with correlation coefficient
      higher than 0.994. Three spiked levels (0.005, 0.05, 0.10 mg/kg) were applied for
      determination of the recoveries of the targets in honey samples in the range of
      80-103% with relative standard deviations not larger than 10.6%. The limits of
      quantification for the analytes ranged between 1.5 and 4.0 MUg/kg. The developed
      method was applied for determination of the target compounds residues in real
      samples.

PMID- 28759150
TI  - Adequate sampling of multiple thyroid nodules by fine-needle aspiration.
AB  - BACKGROUND: Recommendations regarding how many nodules to biopsy with thyroid
      fine-needle aspiration vary. METHODS: The authors reviewed fine-needle aspiration
      specimens of 12,763 nodules from 10,506 patients and correlated them with the
      number of nodules biopsied. RESULTS: Compared with patients in whom only a single
      nodule was biopsied, patients in whom multiple nodules were biopsied were found
      to be significantly younger, more likely female, and to have larger tumors, and
      those tumors were more often papillary (all P<.001). On fine-needle aspiration,
      patients who had multiple nodules biopsied were more often diagnosed with benign
      findings (P<.001), but usually had no significant difference in the risk of
      malignancy associated with any cytologic diagnosis. Performing biopsy in 3
      nodules detected all carcinomas in the current series. Combining all cases in the
      literature demonstrated that performing only 3 biopsies in a patient with at
      least 4 suspicious nodules had a risk of malignancy of 1.2%. CONCLUSIONS: Biopsy
      of 3 different nodules in patients with multiple nodules appears to lower the
      risk of malignancy to that of a benign fine-needle aspiration specimen. Although
      exceptions can occur, cytologists may be able to improve the accuracy of their
      diagnoses by focusing predominantly on identifying papillary carcinoma after the
      first 2 nodules have been biopsied. Cancer Cytopathol 2017;125:848-53. (c) 2017
      American Cancer Society.

PMID- 28759151
TI  - The phenomenology of self-critical thinking in people with depression, eating
      disorders, and in healthy individuals.
AB  - OBJECTIVES: To explore the phenomenology of self-criticism, and the relationship
      with constructs such as rumination and perfectionism. DESIGN: The study followed
      a three-group (Depression, n = 26; Eating Disorder, n = 26; Non-clinical, n = 26)
      mixed methods design. METHOD: Participants completed a set of questionnaires and
      were interviewed about the occurrence, impact, and content of self-critical
      thinking, along with their beliefs about self-criticism. RESULTS: Both clinical
      groups reported more frequent, persistent, and less controllable self-criticism
      compared to controls, present on average 50-60% of the time. They reported a
      negative impact on mood, and a moderately severe impact on daily activities. They
      indicated greater desire to change self-criticism whilst judging it more
      difficult to reduce. Habitual self-criticism was highly correlated with lower
      self-esteem, lower self-compassion, greater rumination, and greater negative
      perfectionism. Compared to those with depression, the eating disorder group
      reported harsher self-criticism, felt it was more part of their personality, and
      was more beneficial. CONCLUSIONS: The findings highlight the importance of
      exploring people's beliefs about their self-criticism, and imply that treatment
      for self-criticism may be more challenging with people with eating disorders than
      people with depression. PRACTITIONER POINTS: This study highlights that self
      criticism is common in depression and eating disorders and that some people find
      this a significant problem in its own right. Careful assessment of self-criticism
      is recommended when working with these clinical presentations, which should
      include the perceived positive consequences and desire to change.

PMID- 28759152
TI  - Anthocyanins from Purple Corn Ameliorated Tumor Necrosis Factor-alpha-Induced
      Inflammation and Insulin Resistance in 3T3-L1 Adipocytes via Activation of
      Insulin Signaling and Enhanced GLUT4 Translocation.
AB  - SCOPE: The aim was to compare the effect of an anthocyanin-rich extract from
      purple corn pericarp (PCW) and pure anthocyanins on adipogenesis, inflammation,
      and insulin resistance in 3T3-L1 adipocytes on basal and inflammatory conditions.
      METHODS AND RESULTS: Preadipocytes (3T3-L1) were treated during differentiation
      with or without PCW. Differentiated adipocytes were treated either individually
      or in combination with tumor necrosis factor alpha (TNF-alpha) and PCW, or pure
      C3G, Pr3G, P3G. PCW reduced preadipocyte differentiation (IC50 = 0.4 mg/mL). PCW
      and pure anthocyanins including C3G reduced fatty acid synthase enzymatic
      activity. PCW reduced TNF-alpha-dependent inflammatory status increasing
      adiponectin (39%), and decreasing leptin (-79%). PCW and C3G increased glucose
      uptake and reduced reactive oxygen species generation in insulin resistant
      adipocytes. An increase in phosphorylation was observed in AKT, IKK, and MEK, and
      a decrease in IRS and mTOR activating the insulin receptor-associated pathway.
      PCW (7.5-fold) and C3G (6.3-fold) enhanced GLUT4 membrane translocation compared
      to insulin resistant adipocytes. CONCLUSION: Anthocyanins from colored corn
      prevented adipocyte differentiation, lipid accumulation, and reduced PPAR-gamma
      transcriptional activity on adipocytes in basal conditions. Ameliorated TNF-alpha
      induced inflammation and insulin resistance in adipocytes via activation of
      insulin signaling and enhanced GLUT4 translocation suggesting a reduced
      hyperglycemia associated with the metabolic syndrome.

PMID- 28759153
TI  - Home ventilator performances with mouthpiece ventilation: Does resistance change
      effectiveness?

PMID- 28759154
TI  - The evolving role of cytopathology in the era of neoadjuvant chemotherapy for the
      accurate pathologic diagnosis of epithelial ovarian cancer.

PMID- 28759155
TI  - Lactate levels and pneumonia severity index are good predictors of in-hospital
      mortality in pneumonia: Methodological issue in cross-sectional study.

PMID- 28759156
TI  - Exclusive right thoracic approach for esophagus surgery.
AB  - An exclusive right thoracic approach for esophagus surgery is rarely used, with
      few reports of its use in China. We retrospectively reviewed the data of 21
      esophageal cancer patients from January 2010 to January 2015. Their age ranged
      from 74-83 years (average 76.6). All of the patients had lower pulmonary
      function. After multidisciplinary team discussion, sufficient preoperative
      preparation, and assessment of cardiopulmonary reserve, an exclusive right
      thoracic approach for esophageal cancer resection was performed. The esophagus
      was dissected in the right chest and the stomach was separated through the
      esophageal hiatus. The tube stomach and the esophageal remnant were anastomosed
      with a stapling device at the top of the right side of the thoracic cavity. All
      operations were successfully completed; however, there were two early
      postoperative deaths resulting from pulmonary infection and pulmonary artery
      embolism. The one-year postoperative survival rate was 66.7%. An exclusive right
      thoracic approach could be selectively used for elderly patients with poor
      pulmonary function.

PMID- 28759157
TI  - mTOR-Notch3 signaling mediates pulmonary hypertension in hypoxia-exposed neonatal
      rats independent of changes in autophagy.
AB  - BACKGROUND/AIM: Mammalian target of rapamycin (mTOR) is a pivotal regulator of
      cell proliferation, survival, and autophagy. Autophagy is increased in adult
      experimental chronic pulmonary hypertension (PHT), but its contributory role to
      pulmonary vascular disease remains uncertain and has yet to be explored in the
      neonatal animal. Notch is a major pro-proliferative pathway activated by mTOR. A
      direct relationship between autophagy and Notch signaling has not been previously
      explored. Our aim was to examine changes in mTOR-, Notch-, and autophagy-related
      pathways and the therapeutic effects of autophagy modulators in experimental
      chronic neonatal PHT secondary to chronic hypoxia. METHODS: Rat pups were exposed
      to normoxia or hypoxia (13% O2 ) from postnatal days 1-21, while receiving
      treatment with temsirolimus (mTOR inhibitor), DAPT (Notch inhibitor), or
      chloroquine (inhibitor of autophagic flux). RESULTS: Exposure to hypoxia up
      regulated autophagy and Notch3 signaling markers in lung, pulmonary artery (PA),
      and PA-derived smooth muscle cells (SMCs). Temsirolimus prevented chronic PHT and
      attenuated PA and SMC signaling secondary to hypoxia. These effects were
      replicated by DAPT. mTOR or Notch inhibition also down-regulated smooth muscle
      content of platelet-derived growth factor beta-receptor, a known contributor to
      vascular remodeling. In contrast, chloroquine had no modifying effects on markers
      of chronic PHT. Knockdown of Beclin-1 in SMCs had no effect on hypoxia-stimulated
      Notch3 signaling. CONCLUSIONS: mTOR-Notch3 signaling plays a critical role in
      experimental chronic neonatal PHT. Inhibition of autophagy did not suppress Notch
      signaling and had no effect on markers of chronic PHT.

PMID- 28759158
TI  - No Sting Barrier Film to Protect Skin in Adult Patients: Findings From a Scoping
      Review With Implications for Evidence-Based Practice.
AB  - BACKGROUND: In the industrialized world, approximately 1-1.5% of the population
      has received treatments for skin lesions. In the 1990s, a polymeric barrier film
      called the No Sting Barrier Film (NSBF) was developed as an alternative to
      petrolatum-based ointments and zinc oxide formulas. To date, few studies have
      explored the effectiveness of NSBF in protecting skin integrity. AIMS: To map the
      methods, fields and outcomes used to produce evidence on NSBF effectiveness.
      METHODS: A scoping review was performed in 2015. A search strategy for
      identifying relevant studies was designed and performed. Systematic reviews, meta
      analyses, randomized controlled trials, controlled clinical trials, and
      comparative studies for all types of interventions were included; research
      conducted in any clinical context was eligible for inclusion. Studies were
      selected by two reviewers; data extraction and analysis also was performed by two
      reviewers and disagreements were discussed. RESULTS: Six studies were included.
      NSBF's potential as a skin protector was investigated with respect to (a) chronic
      wounds (pressure ulcers or vascular leg ulcers); (b) urinary or fecal
      incontinence; and (c) post-mastectomy irradiation. The principal clinical
      outcomes investigated were, respectively: (a) wound healing, wound exudates and
      erythema control; (b) incidence of incontinence-associated dermatitis and skin
      reactions; and (c) intensity of pruritus and skin reactions. Pain and comfort
      were measured in all clinical applications. The main process outcomes
      investigated were: (a) ease of application, (b) application and removal time, and
      (c) costs. Zinc oxide and petroleum formulations were the most common comparison
      interventions in research on chronic ulcers and incontinence; sorbolene cream and
      topical corticosteroids were the most frequent comparisons in the context of post
      mastectomy irradiation. LINKING EVIDENCE TO ACTION: NBSF may be used for peri
      wound skin protection in patients with chronic wounds, with urinary or fecal
      incontinence and for women undergoing post-mastectomy irradiation. However, more
      robust experimental studies are needed in all clinical fields where NBSF is
      applied.

PMID- 28759160
TI  - A Quadruple-Action Platinum(IV) Prodrug with Anticancer Activity Against KRAS
      Mutated Cancer Cell Lines.
AB  - We developed a novel PtIV prodrug that simultaneously releases four different
      bioactive moieties inside the cancer cell. Its cytotoxicity against monolayer
      cultures (2D) and spheroid (3D) cancer cells is significantly better than
      cisplatin. It is 200-450-fold more potent than cisplatin against KRAS mutated
      pancreatic and colon cancers and is 40-fold more selective towards KRAS mutated
      cells compared to non-cancerous. This is important since RAS proteins play a role
      in regulating cell differentiation, proliferation, and survival and KRAS is
      mutated in 90 % of pancreatic adenocarcinomas, 45 % of colorectal cancers, and 35
      % of lung adenocarcinomas. The selectivity index, determined by dividing the IC50
      value in non-cancerous cells by that of a cancerous cell line, is two-fold better
      than cisplatin, attesting to preferential cytotoxicity towards neoplastic cells.

PMID- 28759159
TI  - PeptoSomes for Vaccination: Combining Antigen and Adjuvant in Polypept(o)ide
      Based Polymersomes.
AB  - In this work, the first vaccine is reported based on a PeptoSome, which contains
      a model antigen (SIINFEKL) and adjuvant (CpG). PeptoSomes are polypept(o)ide
      based polymersomes built of a block-copolymer with polysarcosine (PSar) as the
      hydrophilic block (X n = 111) and poly(benzyl-glutamic acid) (PGlu(OBn)) as the
      hydrophobic one (X n = 46). The polypept(o)ide is obtained with low dispersity
      index of 1.32 by controlled ring-opening polymerization. Vesicle formation by
      dual centrifugation technique allows for loading of vesicles up to 40 mol%.
      PeptoSomes are characterized by multiangle dynamic light scattering, static light
      scattering, and cryogenic transmission electron microscopy (cryoTEM). The
      PeptoSomes have a hydrodynamic radius of 39.2 nm with a low dispersity (u 2 =
      0.1). The rho-ratio R g /R h of 0.95 already indicates that vesicles are formed,
      which can be confirmed by cryoTEM. Loaded PeptoSomes deliver the antigen
      (SIINFEKL) and an adjuvant (CpG) simultaneously into dendritic cells (DCs). Upon
      cellular uptake, dendritic cells are stimulated and activated, which leads to
      expression of cluster of differentiation CD80, CD86, and MHCII, but induces
      excretion of proinflammatory cytokines (e.g., TNFalpha). Furthermore, DC-mediated
      antigen-specific T-cell proliferation is achieved, thus underlining the enormous
      potential of PeptoSomes as a versatile platform for vaccination.

PMID- 28759161
TI  - Serine alleviates oxidative stress via supporting glutathione synthesis and
      methionine cycle in mice.
AB  - SCOPE: Serine lies at the central node linking biosynthetic flux from glycolysis
      to glutathione synthesis and one-carbon metabolic cycle which are closely related
      to antioxidant capacity. The present study was conducted to determine the effects
      of serine supplementation on oxidative stress and its relative mechanisms.
      METHODS AND RESULTS: Diquat treatment was performed to induce oxidative stress in
      mice and primary hepatocytes. The results showed that hepatic glutathione anti
      oxidant systems were impaired and reactive oxygen species and homocysteine were
      increased in diquat-induced mice and hepatocytes, while such disadvantageous
      changes were diminished by serine supplementation both in vivo and in vitro.
      However, when cystathionine beta-synthase expression was inhibited by
      interference RNA in hepatocytes, the effects of serine supplementation on the
      improvement of glutathione synthesis and the alleviation of oxidative stress were
      diminished. Moreover, when hepatocytes were treated with cycloleucine, an
      inhibitor of methionine adenosyltransferase, the effects of serine
      supplementation on the improvement of methionine cycle and the alleviation of DNA
      hypomethylation and oxidative stress were also diminished. CONCLUSION: Our
      results indicated that serine supplementation alleviated oxidative stress via
      supporting glutathione synthesis and methionine cycle, mostly by condensing with
      homocysteine to synthesize cysteine and providing one-carbon units for
      homocysteine remethylation.

PMID- 28759162
TI  - Nurses' Perceived Barriers to Bedside Handover and Their Implication for Clinical
      Practice.
AB  - BACKGROUND AND RATIONALE: Bedside handover during the change of shift allows
      nurses to visualize patients and facilitate patient participation, both purported
      to improve patient safety. But, bedside handover does not always occur and when
      it does, it may not involve the patient. AIM: To explore and understand barriers
      nurses perceive in undertaking bedside handover. METHODS: A cross-sectional
      survey was administered to 200 nurses working on medical wards, recruited from
      two Australian hospitals, one private and one public. As part of the survey,
      there was one open-ended question asking about perceived barriers to bedside
      handover. Content analysis was used to analyze data. Barriers were assessed using
      a determinant framework. RESULTS: The open-ended question was answered by 176
      (88%) participants. Three categories were identified. First, censoring the
      message showed nurses were concerned about patients and third-parties hearing
      sensitive information. In the second category, disrupting the communication flow,
      nurses perceived patients, family members, other nurses and external sources,
      interrupted the flow of handover and increased its duration. Finally, inhibiting
      characteristics demonstrated that individual patient and nurse views or
      capabilities hindered bedside handover. Barriers to bedside handover were
      determined to relate to individual nurse factors, patient factors, social,
      political and legal factors, and guideline factors. LINKING EVIDENCE TO ACTION:
      Suggestions for enhancing bedside handover include debunking nurses'
      misconceptions, reflecting on nurses' viewpoints, using active educational
      approaches, and promotion of legal requirements to heighten nurses' confidence
      dealing with sensitive information. Regular patient rounding, and standardized
      handover may enable patient involvement in handover. Finally, reviewing the local
      context to ensure organizational processes support bedside handover is
      recommended.

PMID- 28759163
TI  - New insights into the catalytic mechanism of human glycine N-acyltransferase.
AB  - Even though the glycine conjugation pathway was one of the first metabolic
      pathways to be discovered, this pathway remains very poorly characterized. The bi
      substrate kinetic parameters of a recombinant human glycine N-acyltransferase
      (GLYAT, E.C. 2.3.1.13) were determined using the traditional colorimetric method
      and a newly developed HPLC-ESI-MS/MS method. Previous studies analyzing the
      kinetic parameters of GLYAT, indicated a random Bi-Bi and/or ping-pong mechanism.
      In this study, the hippuric acid concentrations produced by the GLYAT enzyme
      reaction were analyzed using the allosteric sigmoidal enzyme kinetic module.
      Analyses of the initial rate (v) against substrate concentration plots, produced
      a sigmoidal curve (substrate activation) when the benzoyl-CoA concentrations was
      kept constant, whereas the plot with glycine concentrations kept constant, passed
      through a maximum (substrate inhibition). Thus, human GLYAT exhibits mechanistic
      kinetic cooperativity as described by the Ferdinand enzyme mechanism rather than
      the previously assumed Michaelis-Menten reaction mechanism.

PMID- 28759164
TI  - 4D Origami by Smart Embroidery.
AB  - There exist many methods for processing of materials: extrusion, injection
      molding, fibers spinning, 3D printing, to name a few. In most cases, materials
      with a static, fixed shape are produced. However, numerous advanced applications
      require customized elements with reconfigurable shape. The few available
      techniques capable of overcoming this problem are expensive and/or time
      consuming. Here, the use of one of the most ancient technologies for structuring,
      embroidering, is proposed to generate sophisticated patterns of active materials,
      and, in this way, to achieve complex actuation. By combining experiments and
      computational modeling, the fundamental rules that can predict the folding
      behavior of sheets with a variety of stitch-patterns are elucidated. It is
      demonstrated that theoretical mechanics analysis is only suitable to predict the
      behavior of the simplest experimental setups, whereas computer modeling gives
      better predictions for more complex cases. Finally, the applicability of the
      rules by designing basic origami structures and wrinkling substrates with
      controlled thermal insulation properties is shown.

PMID- 28759166
TI  - Altered metabolites of the rat hippocampus after mild and moderate traumatic
      brain injury - a combined in vivo and in vitro 1 H-MRS study.
AB  - Traumatic brain injury (TBI) has been shown to affect hippocampus-associated
      learning, memory and higher cognitive functions, which may be a consequence of
      metabolic alterations. Hippocampus-associated disorders may vary depending on the
      severity of injury [mild TBI (miTBI) and moderate TBI (moTBI)] and time since
      injury. The underlying hippocampal metabolic irregularities may provide an
      insight into the pathological process following TBI. In this study, in vivo and
      in vitro proton magnetic resonance spectroscopy (1 H-MRS) data were acquired from
      the hippocampus region of controls and TBI groups (miTBI and moTBI) at D0 (pre
      injury), 4 h, Day 1 and Day 5 post-injury (PI). In vitro MRS results indicated
      trauma-induced changes in both miTBI and moTBI; however, in vivo MRS showed
      metabolic alterations in moTBI only. miTBI and moTBI showed elevated levels of
      osmolytes indicating injury-induced edema. Altered levels of citric acid cycle
      intermediates, glutamine/glutamate and amino acid metabolism indicated injury
      induced aberrant bioenergetics, excitotoxicity and oxidative stress. An overall
      similar pattern of pathological process was observed in both miTBI and moTBI,
      with the distinction of depleted N-acetylaspartate levels (indicating neuronal
      loss) at 4 h and Day 1 and enhanced lactate production (indicating heightened
      energy depletion leading to the commencement of the anaerobic pathway) at Day 5
      in moTBI. To the best of our knowledge, this is the first study to investigate
      the hippocampus metabolic profile in miTBI and moTBI simultaneously using in vivo
      and in vitro MRS.

PMID- 28759167
TI  - Small but Mighty: Functional Peptides Encoded by Small ORFs in Plants.
AB  - Peptides encoded by small open reading frames (sORFs, usually <100 codons) play
      critical regulatory roles in plant development and environmental responses.
      Despite their importance, only a small number of these peptides have been
      identified and characterized. Genomic studies have revealed that many plant
      genomes contain thousands of possible sORFs, which could potentially encode small
      peptides. The challenge is to distinguish translated sORFs from nontranslated
      ones. Here, we highlight advances in methodologies for identifying these hidden
      sORFs in plant genomes, including ribosome profiling and proteomics. We also
      examine the evidence for new peptides arising from sORFs and discuss their
      functions in plant development, environmental responses, and translational
      control.

PMID- 28759169
TI  - Erratum.

PMID- 28759168
TI  - Decelerating flow shape for volume-targeted mouthpiece ventilation.

PMID- 28759170
TI  - Is oral contraceptive use associated with an increased risk of cervical cancer?
      An evidence-based meta-analysis.
AB  - AIM: The purpose of this meta-analysis is to synthesize evidence-based case
      control studies to evaluate the association between oral contraceptive (OC) use
      and the risk of cervical cancer. METHODS: Two reviewers independently selected
      potentially relevant studies through PubMed, Embase, Chinese National Knowledge
      Infrastructure, Wanfang Data, and the Chongqing VIP databases using the core
      terms cervical intraepithelial neoplasia/ cervix dysplasia/ cervi* AND oral
      contraceptive in the article titles, abstracts, and keywords. All data were
      analyzed using stata 12.0. The heterogeneity was assessed by Q-test and I2
      statistic. Forest plot was used to display results graphically. Publication bias
      was assessed by Begg's test. RESULTS: In total, 16 case-control studies,
      including 15 619 participants (7433 cases and 8186 controls), met the eligibility
      criteria. Individuals with OC use were not found to have a risk of cervical
      cancer (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.90-1.38). In
      subgroup analyses, no significant associations were found for different durations
      of OC use (<5 years: OR, 0.84; 95%CI, 0.68-1.04; 5-10 years: OR, 1.06; 95%CI,
      0.66-1.71; >10 years: OR, 1.25; 95%CI, 0.76-2.06). Additionally, using OC was not
      shown to increase the risk of cervical cancer among women with human
      papillomavirus infections (OR, 1.09; 95%CI, 0.80-1.49). However, an increased
      risk of cervical cancer was found in Asian populations with OC use. CONCLUSION:
      The meta-analysis of case-control studies did not show an association between OC
      use and risk of cervical cancer. However, other necessary prospective cohort
      studies should be conducted to assess the impact of OC use on cervical cancer
      risk in the future.

PMID- 28759171
TI  - Identification of potential crucial genes associated with early-onset pre
      eclampsia via a microarray analysis.
AB  - AIM: This study aimed to identify potential key genes related to early-onset pre
      eclampsia (EOPET), and to obtain a better understanding of the molecular
      mechanisms of this disease. METHODS: The microarray dataset GSE44711 was obtained
      from the Gene Expression Omnibus, including eight chorionic villi samples from
      EOPET placentas and eight normal controls. The differentially expressed genes
      (DEG) were identified using the LIMMA package, and their potential functions were
      predicted by Gene Ontology (GO) enrichment analysis. Furthermore, protein-protein
      interactions (PPI) were obtained from the STRING database, and the PPI network
      was visualized by Cytoscape software. Then, significant modules were screened out
      from the PPI network, and GO enrichment analysis for DEG in modules was
      performed. Also, the potential transcription factors (TF) regulating DEG in
      modules were predicted, and TF-DEG network was visualized by Cytoscape. RESULTS:
      A total of 270 upregulated and 200 downregulated DEG were identified. A set of
      DEG was related to functions such as female pregnancy and hormone metabolic
      process (e.g. NGF). In PPI network modules, some DEG (e.g. SERPINE1 and FN1) were
      significantly associated with anatomical structure morphogenesis, and some other
      DEG (e.g. GZMA) were relevant to the immune system process. Furthermore,
      SERPINE1, NGF, and FN1 interacted with each other and were regulated by RELA.
      CONCLUSION: The DEG related to hormone metabolic process (e.g. NGF), anatomical
      structure morphogenesis (e.g. SERPINE1 and FN1), and immune system process (e.g.
      GZMA) are predicted to play significant roles in the progress of EOPET, which
      will be confirmed by experiments in future.

PMID- 28759172
TI  - Assessment of oxidative stress markers in cord blood of newborns to patients with
      oxytocin-induced labor.
AB  - AIM: We aimed to measure the extent of oxidative stress experienced during labor
      by the neonates of pregnant women undergoing induced or spontaneous birth and to
      compare the effects of induced labor on fetal well-being. METHODS: Sixty-four
      healthy pregnant women referring to the Department of Gynecology and Obstetrics,
      Dicle University Medical Faculty between October 2010 and May 2011 were included
      in this comparative study. Pregnant women undergoing induced labor by oxytocin
      were group 1 and those without labor induction were group 2. Post-partum Apgar
      score was calculated at 1 and 5 min and measurements of weight and height of the
      neonates were carried out. After the fetal cord was clamped, 5 cm3 blood was
      drawn into a plain tube without anticoagulant. The samples were centrifuged at
      5000 r.p.m. for 5 min. Separated sera were transferred to Eppendorf tubes and
      were stored at -80 C degrees  until the analysis time. RESULTS: The complete
      blood counts and biochemistry results indicated that there were no statistically
      significant differences in regards to diseases between the two groups. Nitric
      oxide and asymmetrical dimethylarginine values of the two groups were not
      significantly different; however, there were statistically significant
      differences in the malondialdehyde, paraoxonase, total antioxidative status, and
      total oxidative status values of the two groups (respectively, P = 0.005, P =
      0.006, P = 0.008, and P = 0.007). CONCLUSION: We observed that oxytocin-induced
      labor increases stress markers but does not affect Apgar scores. Oxidative stress
      in pregnant women may trigger antioxidative mechanisms. Prospective studies in
      larger cohorts are needed to better understand the impact of oxytocin-induced
      labor on pregnant women and neonates.

PMID- 28759173
TI  - Direct online extraction and determination by supercritical fluid extraction with
      chromatography and mass spectrometry of targeted carotenoids from red Habanero
      peppers (Capsicum chinense Jacq.).
AB  - Recently, supercritical fluid chromatography coupled to mass spectrometry has
      gained attention as a fast and useful technology applied to the carotenoids
      analysis. However, no reports are available in the literature on the direct
      online extraction and determination by supercritical fluid extraction with
      chromatography and mass spectrometry. The aim of this research was the
      development of an online method coupling supercritical fluid extraction and
      supercritical fluid chromatography for a detailed targeted native carotenoids
      characterization in red habanero peppers. The online nature of the system,
      compared to offline approaches, improves run-to-run precision, enables the
      setting of batch-type applications, and reduces the risks of sample
      contamination. The extraction has been optimized using different temperatures,
      starting from 40 degrees C up to 80 degrees C. Multiple extractions, until
      depletion, were performed on the same sample to evaluate the extraction yield.
      The range of the first extraction yield, carried out at 80 degrees C, which was
      the best extraction temperature, was 37.4-65.4%, with a %CV range of 2-12. Twenty
      one targeted analytes were extracted and identified by the developed methodology
      in less than 17 min, including free, monoesters, and diesters carotenoids, in a
      very fast and efficient way. Quantification of the beta-carotene was carried out
      by using the optimized conditions.

PMID- 28759175
TI  - Oxytocin Use in Labor: Risks, Benefits, and Guidelines (2017/039).

PMID- 28759174
TI  - Next-generation learning and training: The Cy-TEST experience.

PMID- 28759176
TI  - Midwifery Is Not Obstetrics: The Importance of Precise Maternity Care Language.

PMID- 28759177
TI  - Breastfeeding Outcomes After Oxytocin Use During Childbirth: An Integrative
      Review.
AB  - INTRODUCTION: Despite widespread use of exogenous synthetic oxytocin during the
      birth process, few studies have examined the effect of this drug on
      breastfeeding. Based on neuroscience research, endogenous oxytocin may be altered
      or manipulated by exogenous administration or by blocking normal function of the
      hormone or receptor. Women commonly cite insufficient milk production as their
      reason for early supplementation, jeopardizing breastfeeding goals. Researchers
      need to consider the role of birth-related medications and interventions on the
      production of milk. This article examines the literature on the role of exogenous
      oxytocin on breastfeeding in humans. METHODS: Using the method described by
      Whittemore and Knafl, this integrative review of literature included broad search
      criteria within the PubMed, Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), Cochrane, and Scopus databases. Studies published in English
      associating a breastfeeding outcome in relation to oxytocin use during the birth
      process were included. Twenty-six studies from 1978 to 2015 met the criteria.
      RESULTS: Studies were analyzed according to the purpose of the research, measures
      and methods used, results, and confounding variables. The 26 studies reported 34
      measures of breastfeeding. Outcomes included initiation and duration of
      breastfeeding, infant behavior, and physiologic markers of lactation. Timing of
      administration of oxytocin varied. Some studies reported on low-risk birth, while
      others included higher-risk experiences. Fifty percent of the results (17 of 34
      measures) demonstrated an association between exogenous oxytocin and less optimal
      breastfeeding outcomes, while 8 of 34 measures (23%) reported no association. The
      remaining 9 measures (26%) had mixed findings. Breastfeeding intentions, parity,
      birth setting, obstetric risk, and indications for oxytocin use were
      inconsistently controlled among the studies. DISCUSSION: Research on
      breastfeeding and lactation following exogenous oxytocin exposure is limited by
      few studies and heterogeneous methods. Despite the limitations, researchers and
      clinicians may benefit from awareness of this body of literature. Continued
      investigation is recommended given the prevalence of oxytocin use in clinical
      practice.

PMID- 28759178
TI  - Mutations in AXIN2 gene as a risk factor for tooth agenesis and cancer: A review.
AB  - AXIN2 gene plays a crucial role in morphogenesis of craniofacial area and is
      essential for tooth development. AXIN2 gene is one of the most studied genes
      associated with tooth agenesis, the most common defect of dentition in humans.
      Polymorphic variants in AXIN2 gene are discussed in relation to the occurrence of
      the tooth agenesis but also as an indication of the risk of cancer. Mutations in
      AXIN2 gene were found in patients with colorectal or hepatocellular carcinoma,
      prostate cancer, ovarium or lung cancer. These findings support the hypothesis
      that missing teeth may be a significant marker for predisposition for cancer.

PMID- 28759179
TI  - Neonatal Marfan syndrome: Report of two cases.
AB  - Marfan syndrome is rarely diagnosed in the neonatal period because of variable
      expression and age-dependent appearance of clinical signs. The prognosis is
      usually poor due to high probability of congestive heart failure, mitral and
      tricuspid regurgitations with suboptimal response to medical therapy and
      difficulties in surgical management. The authors have studied two cases of Marfan
      syndrome in the newborn period. Two cases of neonatal Marfan syndrome, one male
      and one female, were diagnosed by characteristic physical appearance. Both
      infants had significant cardiovascular abnormalities diagnosed by
      ultrasonography. Genetic DNA analysis in the second case confirmed the mutations
      in the fibrillin-1 gene located on chromosome 15q21 which is responsible for the
      development of Marfan syndrome. The boy died at six weeks of age with signs of
      rapidly progressive left ventricular failure associated with pneumonia. The
      second infant was having only mild signs of congestive heart failure and has been
      treated with beta blockers. At the age of 4 years her symptoms of congestive
      heart failure had worsened due to progression of mitral and tricuspid
      insufficiency and development of significant cardiomegaly. Mitral and tricuspid
      valvuloplasy had to be done at that time. Early diagnosis of Marfan syndrome in
      the newborn period can allow treatment in the early stages of cardiovascular
      abnormalities and may improve the prognosis. It also helps to explain to the
      family the serious health problem of their child.

PMID- 28759180
TI  - Central hypoadrenocorticism associated with Rathke's cleft cyst.
AB  - Rathke's cleft cysts (RCCs) are non-neoplastic, sellar or suprasellar epithelium
      lined cysts originating from Rathke's pouch in the pituitary gland. Patients with
      RCCs are usually asymptomatic, but some have only been identified when symptoms
      manifested in middle age. The characteristics of these patients during childhood
      or adolescence remains unknown. We describe an 18-year-old girl who had
      occasionally suffered from malicious fatigue in the morning since her early
      teens. Brain magnetic resonance imaging (MRI) revealed T1 hyperintense/T2
      hypointense signals between the anterior and posterior pituitary glands,
      indicating the presence of RCC. Based on an authentic endocrinological
      evaluation, her adrenal function seemed normal; nevertheless, her serum cortisol
      level strangely dropped around noon. Furthermore, daily supplementation of oral
      hydrocortisone bizarrely suppressed ACTH secretion to below the detection range
      in the morning. These data appeared compatible with the presence of central
      adrenal dysfunction. We also review the literature for previously reported cases.
      In conclusion, the symptoms and endocrinological data for dysfunction of the
      hypothalamic pituitary system might be non-specific and vary among patients,
      especially in teenagers. Brain MRI and daily cortisol profiling in blood are key
      to obtaining a diagnosis of an impaired hypothalamic adrenal function due to RCC.

PMID- 28759181
TI  - Cognitive function and depressivity before and after cpap treatment in
      obstructive sleep apnea patients.
AB  - OBJECTIVE: The target of the investigation was to find if there is any
      improvement of depressive symptoms and cognitive functioning after continuous
      positive airway pressure (CPAP) treatment in the severe obstructive apnea (OSA)
      patients. METHOD: The study included 59 patients treated with CPAP for OSA in the
      Sleep Laboratory of the Department of Respiratory Medicine. Thirty-eight patients
      were treated with CPAP for one month, and twenty-one patients were in a control
      group. We used the following methods: Test of Visual Memory (ViMe), Numeric
      Rectangle, d2 (test of attention), and the Beck Depression Inventory-II,
      respectively. RESULTS: Among the OSA patients, there were statistically
      significant improvements in all parameters: attention, working memory, and
      depressive symptoms after the treatment with CPAP. We found a statistically
      significant positive connection between the decrease in depressive symptoms and
      the improvement in attention. In the control group, there were no improvements in
      the investigated factors. CONCLUSIONS: According to our results, the patients
      with sleep apnoea improved their mood and cognitive functions during the
      treatment by the CPAP device.

PMID- 28759183
TI  - Co-administration of Cyclosporin A and Ondansetron decreases transient local
      cerebral ischemic injury in the mouse.
AB  - OBJECTIVES: Several studies indicate that cyclosporin A has a protective effect
      against brain infarction. In this study, we aimed to determine if co
      administration of cyclosporin A and ondansetron could reduce damage caused by
      cerebral ischemia. METHODS: ICR (Charles River Laboratories) mice were subjected
      to transient focal cerebral ischemia and divided into 4 groups (O, V, C, and
      Mix). Immediately after reperfusion, each ligand was administered intravenously
      through the external jugular vein. Group V animals received 0.9% saline alone,
      group O animals received 0.1 mg/kg ondansetron solution, group C animals received
      10 mg/kg cyclosporin A solution, and group Mix received 0.1 mg/kg ondansetron
      solution and 10 mg/kg cyclosporin A solution. RESULTS: Our results showed that
      the volume of brain infarction induced by middle cerebral artery occlusion in
      group Mix was significantly smaller than that seen in group V. Forty-eight hours
      after ischemia, the neurological scores of rats from group Mix significantly
      improved when compared to group V. CONCLUSION: Overall, our study showed that a
      combination of cyclosporin A and ondansetron may be a practical clinical method
      to treat brain infarction. However, further studies are required to investigate
      the cerebroprotective mechanism of action, the possible side effects of co
      administration of these drugs, and the ability of these ligands to cross the
      blood brain barrier.

PMID- 28759182
TI  - Intima media thickness of common carotids and abdominal aorta in children and
      adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
      in relation to their genotypes.
AB  - BACKGROUND: Patients with congenital adrenal hyperplasia (CAH) are at risk of
      vascular and metabolic complications due to steroid therapy and increased adrenal
      androgens exposure. OBJECTIVE: of the study was to evaluate the relation between
      patient's genotype and (1) intima media thickness of abdominal aorta (AIMT) and
      common carotid arteries (CIMT) and (2) metabolic profile. MATERIAL AND METHODS:
      In 71 patients (27 boys) aged from 1.5 to 17.9 years, with 21-hydroxylase
      deficiency (21OHD) CAH: 9 with nonclassic (NC) CAH, 62 with classic CAH: 10 with
      simple virilising (SV) and 52 with salt wasting (SW) CAH (13-Del/Del, 8-Del/I2G,
      7-I2G/I2G and 24-other genotypes), and in 77 lean and 36 normotensive obese, age
      and gender matched controls, assessment of CIMT and AIMT as well as hormonal and
      biochemical evaluation were performed. RESULTS: The highest AIMT was observed in
      SW Del/Del and I2G/I2G groups and the highest CIMT in SV CAH subgroup. CIMT and
      AIMT correlated significantly with testosterone and free androgen index (FAI),
      and were significantly higher in patients with advanced bone age and obesity
      independent. Significantly higher HOMA, testosterone and FAI values were found in
      SV CAH. CONCLUSION: In CAH patients CIMT and AIMT are influenced by androgens and
      obesity independent. In the examined group vascular and metabolic abnormalities
      are pronounced more in certain subgroups of CAH (SV and SW: Del/Del) and in
      patients with advanced bone age.

PMID- 28759184
TI  - Is non-pharmacological treatment an effective option for chronic low back pain?
AB  - OBJECTIVE: Despite of pain being important warning signal for body ability to
      respond to internal or external threats, chronic pain is perceived as a
      discomfort by patients, leading to somatic, emotional and social negative
      changes. Lifestyle, wrong seating habits and some occupations may contribute to
      chronic back pain. Therapy for chronic back pain should include not only
      pharmacological or invasive interventions, but mostly change of lifestyle,
      physiotherapy and non-pharmacological methods. METHODS: The main objective of the
      paper was to compare subjective perception of the effectiveness of various
      methods for treatment of low back pain. In total, 100 patients were asked to fill
      the questionnaire after completing the treatment, whether conventional or non
      pharmacological. We have aimed to analyze not only the perception of the
      patients, but also indicators of the patient's lifestyle, their nutrition and
      physical activity. RESULTS: Oral drugs was the most effective option perceived by
      the patients, followed by non-pharmacological methods, such as massages, heat
      application and acupuncture. At the same time, all patients who changed their
      lifestyle, for example reduced smoking and alcohol and increased physical
      activity, achieved better results in non-pharmacological treatment and
      experienced higher pain alleviation compared to the patients treated by
      medications only. CONCLUSION: Non-pharmacological therapy of chronic non
      malignant low back pain could be an effective option offered in combination with
      medicaments and change of lifestyle.

PMID- 28759185
TI  - Serum FGF21 in girls with anorexia nervosa - comparison to normal weight and
      obese female adolescents.
AB  - BACKGROUND: Fibroblast growth factor 21 (FGF21) is a hepatokine, myokine and
      adipokine of a potent influence to energy homeostasis. Data according its serum
      concentrations in AN are contradictory. OBJECTIVES: Analysis of serum FGF21 in
      girls with acute anorexia nervosa and comparison the results with normal weight
      and obese female adolescents considering their nutritional status, carbohydrate
      and lipid metabolism. METHODS: Serum FGF21 concentrations were evaluated using
      commercially available ELISA kit in 32 Polish girls with restrictive AN (AN), 29
      girls with obesity (O) and 21 healthy controls (C). Anthropometric measurements
      (weight, height, BMI) and laboratory assays (serum fasting glucose, insulin, HOMA
      IR, total cholesterol, HDL, LDL, triglycerides, C-reactive protein) were
      performed. RESULTS: Mean serum FGF-21 in the AN group was significantly lower,
      whereas in the O group it was significantly higher than in healthy controls. In
      all examined girls significant positive correlations between FGF21 and BMI were
      noted. We also observed significant positive relationships between serum FGF21
      levels and fasting glucose, triglycerides, CRP, insulin and HOMA-IR. In all
      examined girls serum concentrations of this hormone correlated negatively with
      age and HDL-cholesterol levels. CONCLUSIONS: 1) Serum FGF21 concentrations are
      decreased in AN and elevated in obesity. They are independently and positively
      related to BMI and insulin resistance; 2) Decreased serum FGF21 in AN may support
      the maintenance of normal blood glucose through adjustment the insulin levels and
      insulin sensitivity; 3) Elevated FGF21 levels in obesity may be considered
      adaptive mechanism preventing insulin resistance and its metabolic consequences.

PMID- 28759186
TI  - Endocrine and haemodynamic stress responses to an arithmetic cognitive challenge.
AB  - OBJECTIVE: We aimed at developing and validating a simple, highly repeatable
      computer-based tool, which could be employed to simulate the effects of an acute
      mental stress on endocrine and haemodynamic stress responses. METHODS: Fifteen
      subjects underwent a mental cognitive challenge, employing an ad hoc designed web
      tool (available at http://bagame.altervista.org) that proposed a series of random
      arithmetic operations (addictions or subtractions) between one- to three-digit
      numbers for 10 minutes. We measured plasma epinephrine, norepinephrine, cortisol,
      and ACTH, in addition to heart rate (HR), systolic (SBP) and diastolic (DBP)
      blood pressure throughout the test. RESULTS: The arithmetic mental challenge
      promptly activated the sympatho-adrenomedullary axis (epinephrine +112+/-24%,
      p<0.05; norepinephrine +37+/-13%, p<0.004) and the hypothalamic-pituitary
      adrenocortical axis (cortisol +25+/-7%, p<0.008; ACTH +97+/-44%, p<0.008), which
      in turn exerted stimulatory effects on the cardiovascular system (HR +18+/-4%,
      p<0.05; SBP +112+/-24%, p<0.05; DBP +34+/-8%, p<0.05) in all subjects, without
      any symptoms and regardless of the individuals' mental arithmetic ability.
      CONCLUSIONS: We developed and validated a computer-based tool that is effective
      for simulating endocrine and haemodynamic responses to an acute mental stress.
      This novel tool is easy-to-use, freely-accessible, and it can be employed to
      further investigate stress-related pathophysiological mechanisms and their role
      in cardiovascular diseases.

PMID- 28759187
TI  - A Chinese herbal medicine (Modified Guomin Decoction) Influences the
      differentiation of CD4+ T-cell subsets in OVA-induced asthmatic mice.
AB  - OBJECTIVE: Modified Guomin Decoction (MGD) is an effective Chinese herbal
      medicine for treatment of various allergic diseases, especially allergic asthma.
      Its water decoction is conventionally used for treatment of allergic bronchitis
      in China. Up to date, the underlying mechanisms of this herbal combination have
      not been fully investigated yet. METHODS: In the in vivo study, the mice were
      treated with Chicken egg ovalbumin (OVA) and aluminum hydroxide gel as the
      classic allergic asthma animal model. After treatment with MGD, the lung tissues
      were examined by Histological assessment. The flow cytometric analysis was used
      to classify the CD4+ T-cell subsets. RT-PCR, Real time fluorescence quota PCR and
      Western blotting were used to analyze the gene expression of IL-4, IL-5, IFN
      gamma T-bet/GAIA-3 and Foxp3 in lung tissues. RESULTS: MGD significantly reduced
      ovalbumin-specific IgE production in mouse serum and suppressed inflammatory cell
      infiltration, thus, improved the asthma symptoms. The mechanistic studies
      indicated that MGD treatment mainly modified the differentiation of CD4+ T-cell
      subsets and improved their functions. These included that MGD enhanced the
      proportion of Th1-cell, reduced Th2-cell subsets to CD4+ cell and balanced
      Treg/Th17 cell populations in the asthmatic mice spleen tissues. For Th1-cells,
      MGD upregulated the gene expression of their cytokine IFN-gamma and its
      transcription factor T-bet while it downregulated the gene expression of their
      cytokines of IL-4 and IL-5. For Th2-cells, MGD mainly downregulated its
      transcription factor GATA-3 in lung tissues of asthmatic mice. MGD suppressed the
      Th17-cell subsets in CD4+ cells and upregulated the expression of Foxp3, a
      specific transcription factor of Treg-cell.

PMID- 28759188
TI  - Selected mechanical paremeters of women's hair in the Caucasian population.
AB  - OBJECTIVE: More parameters have been used for more detailed description of
      mechanical properties of human hair as a fibre than in analogous studies. All
      measured samples were taken from five different locations on the heads of 60
      women of varied age. METHODS: For each hair, the diameter was determined
      optically and then the test in the Deform Type 2 testing machine was carried out.
      Deformation curves were obtained by testing 10 mm long samples up to the rupture
      point at constant temperature, humidity and constant crossbar speed of 2 mm/min.
      The curves were processed with software for the calculation of mechanical
      parameters of the hairs. This specialized software has been designed by us for
      that purpose. Resulting values were arranged into tables and figures. RESULTS: As
      far as hair cross-section is concerned, it has been found that for the European
      population it appears to be rather higher - 86 MUm - than indicated in formerly
      published texts. The 56 MUm mentioned in the work of other authors has been
      observed only utterly exceptionally, in 0.3 % of the population. All quantities
      studied (except extensibility) display moderate to strong positive skewness in
      comparison to Gauss distribution. The most marked skewness is seen in the
      resilience. At the same time, this quantity displays the highest value of non
      Gaussian distribution. The elasticity module of 2.3+/-0.6 GPa is three times
      lower than the one reported by other authors, yet according to the fact published
      in our work - which shows unambiguously that the thinner the hair, the higher
      elasticity module it displays - the value of 7.2 GPa for the 56 um thick hairs is
      comparable and it confirms the hypothesis that the cortex, which is responsible
      for the mechanical strength of the hair, is contained in a higher ratio in
      thinner hairs. This similarly applies to the ultimate strength; the linearity
      limit is hard to compare with literature, as it almost does not appear there.
      CONCLUSION: By measuring 886 samples from the heads of 60 adult women of European
      type, it was possible to ascertain the current norm for a larger number of
      mechanical parameters of the hairs. Further merit of this work is the fact that
      the hairs were taken systematically from five well-defined places of the studied
      heads in equal count, which is an aspect formerly published works do not respect
      and they do not present the location of sampling.

PMID- 28759189
TI  - Carotid intima-media thickness in plaque-free area, carotid plaque and risk of
      ischemic stroke in high-risk population of North China.
AB  - OBJECTIVE: Stroke is the leading cause of mortality and acquired disability in
      adults in China. In this study, we investigated the role of carotid artery intima
      media thickness (IMT) and carotid plaques in new ischemic stroke of high-risk
      population in North China. METHODS: The study was conducted in 4 towns in North
      China area. Subjects with three or more cardiovascular risk factors such as
      hypertension, dyslipidemia (or unknown), diabetes mellitus, currently smoking,
      over weight, family history of stroke, with a history of transient ischemic
      attack (TIA) and ischemic stroke were included in this study. The demographic
      data, carotid artery-IMT and number of segments with plaques (NSP) was recorded
      when they were recruited. The new ischemic stroke was recorded in 2129 subjects
      after 2.1 year's follow up. Risk analysis was performed between subject with or
      without new ischemic stroke. RESULTS: There were 69 new cases occurred ischemic
      stroke. The proportion of hypertension, ischemic stroke history and the plaque
      numbers were significantly higher in subjects with new ischemic strokes than
      those without new ischemic strokes. Cox regression showed remarkable positive
      correlation between the incidence of new ischemic stroke events with the presence
      of plaque as well as increased NSP. However, the increasing quartiles of common
      carotid artery intima-media thickness (CCA-IMT) has no difference in occurrence
      of new ischemic stroke events. CONCLUSION: Screening of carotid artery especially
      for carotid artery plaques should be taken into consideration among people with
      high risk of ischemic stroke.

PMID- 28759190
TI  - Genetic polymorphisms and serum concentrations of adiponectin and resistin in
      anorexia nervosa and healthy controls - pilot study.
AB  - BACKGROUND: A possible role of adipokines in the regulation of body weight in
      patients with anorexia nervosa (AN) has been proposed. Polymorphisms in genes
      encoding adiponectin and resistin in AN have not been widely assessed, yet.
      OBJECTIVES: 1) Assessment the frequency of ADIPOQ c.45T>G, ADIPOQ c.276G>T
      polymorphisms in adiponectin and RETN c.62G>A, RETN c.-180C>G in resistin genes
      in AN patients and control group (C) 2) Analysis of correlation between these
      polymorphisms and serum ADP or RETN. METHODS: We examined 67 AN girls and 38 C
      aged 11-18. Analyses of polymorphisms in ADIPOQ and RETN genes were performed
      using RFLP method and adiponectin and resistin serum levels - with commercially
      available ELISA kits. RESULTS: In AN subjects, TT genotype in ADIPOQ c.276
      polymorphism as well as GG genotype of RETN c.-180 were significantly more
      frequent than in CG. In ADIPOQ c.45 polymorphic site, TT alleles were the most
      frequent in both examined groups. In RETN c.62 GA and GG alleles distribution did
      not differ between the groups and the most frequently observed genotype was GG.
      The mean serum adiponectin level in AN was significantly higher and resistin -
      lower than in controls. There were no statistically significant relationships
      between serum adiponectin and resistin levels and allele frequency in
      polymorphisms ADIPOQ c.276 as well as RETN c.-180 in the examined groups.
      CONCLUSION: Differences in genotype frequencies of ADIPOQ c.276 and RETN c.-180
      suggest a need for studies on a larger cohort of patients with AN.

PMID- 28759191
TI  - Effects of age on the glucoregulatory response following acute glucoprivation
      induced by 2-deoxyglucose (2DG) in the adrenal medulla of Sprague Dawley rats.
AB  - OBJECTIVES: Impairment in glucose homeostasis is one of the factors that may
      alter the feeding drive, hunger and satiety signals, which essential to maintain
      a sufficient level of energy for daily activities especially among the elderly.
      Adrenal medulla is one of the important organs that involves in glucose
      homeostasis through secretion of catecholamines. The catecholamines biosynthesis
      pathway utilizes various enzymes and protein kinases. The aims of this study are
      to investigate the effects of age on the biosynthetic pathway of catecholamines
      in adrenal medulla by determining the level of blood glucose and blood
      catecholamines, the gene and protein expression of biosynthetic catecholamine
      enzymes (TH, DBH and PNMT) as well as protein kinase substrates that involved in
      the phosphorylation of TH in 2DG-induced rats. METHODS: Adrenal medulla from male
      Sprague Dawley rats at the age of 3-months (n=12) and 24-months (n=12) were
      further divided into two groups: 1) treatment group with 2DG to create
      glucoprivation condition and 2) the vehicle group which received normal saline as
      control. RESULTS: The results showed that the level of glucose, adrenaline and
      noradrenaline were increased in response to acute glucoprivation conditions in
      both young and old rats. No age-related differences were found in the basal gene
      expression of the enzymes that involved in the catecholamines biosynthesis
      pathway. Interestingly the expressions of TH and DBH protein as well as the level
      of TH phosphorylation at Ser40, PKA, PKC and ERK1/2 substrates were higher in
      basal condition of the aged rats. However, contradicted findings were obtained in
      glucoprivic condition, which the protein expressions of DBH, pERK1/2 and
      substrates for pPKC were increased in young rats. Only substrate for pCDK was
      highly expressed in the old rats in the glucoprivic condition, while pPKC and
      pERK1/2 were decreased significantly. The results demonstrate that adrenal
      medulla of young and old rats are responsive to glucose deficit and capable to
      restore the blood glucose level by increasing the levels of blood catecholamines.
      CONCLUSION: The present findings also suggest that, at least in rats, aging
      alters the protein expression of the biosynthetic catecholamine enzymes as well
      as protein kinase substrates that may attenuate the response to glucoprivation.

PMID- 28759194
TI  - Nanoscale Phase-Separated Structure in Core-Shell Nanoparticles of SiO2-Si1
      xGexO2 Glass Revealed by Electron Microscopy.
AB  - SiO2-based optical fibers are indispensable components of modern information
      communication technologies. It has recently become increasingly important to
      establish a technique for visualizing the nanoscale phase-separated structure
      inside SiO2-GeO2 glass nanoparticles during the manufacturing of SiO2-GeO2
      fibers. This is because the rapidly increasing price of Ge has made it necessary
      to improve the Ge yield by clarifying the detailed mechanism of Ge diffusion into
      SiO2. However, direct observation of the internal nanostructure of glass
      particles has been extremely difficult, mainly due to electrostatic charging and
      the damage induced by electron and X-ray irradiation. In the present study, we
      used state-of-the-art scanning electron microscopy (SEM), scanning transmission
      electron microscopy (STEM), and energy dispersive X-ray spectroscopy (EDX) to
      examine cross-sectional samples of SiO2-GeO2 particles embedded in an epoxy
      resin, which were fabricated using a broad Ar ion beam and a focused Ga ion beam.
      These advanced techniques enabled us to observe the internal phase-separated
      structure of the nanoparticles. We have for the first time clearly determined the
      SiO2-Si1-xGexO2 core-shell structure of such particles, the element distribution,
      the degree of crystallinity, and the quantitative chemical composition of
      microscopic regions, and we discuss the formation mechanism for the observed
      structure. The proposed imaging protocol is highly promising for studying the
      internal structure of various core-shell nanoparticles, which affects their
      catalytic, optical, and electronic properties.

PMID- 28759196
TI  - Janus Mesoporous Silica Nanoparticles for Dual Targeting of Tumor Cells and
      Mitochondria.
AB  - The development of targeted nanocarriers able to be selectively internalized
      within tumor cells, and therefore to deliver anti-tumor drugs specifically to
      diseased cells, constitutes one of the most important goals in nano-oncology.
      Herein, the development of Janus mesoporous silica particles asymmetrically
      decorated with two targeting moieties, one of them selective for folate membrane
      cell receptors (folic acid) and the other one able to bind to mitochondria
      membrane (triphenylphosphine, TPP), is described in order to achieve sequential
      cell to organelle vectorization. The asymmetric decoration of each side of the
      particle allows fine control in the targeting attachment process in comparison
      with the use of symmetric nanocarriers. The presence of folic acid induces a
      higher increase in particle accumulation inside tumor cells, and once there,
      these nanocarriers are guided close to mitochondria by the action of the TPP
      moiety. This strategy can be applied for improving the therapeutic efficacy of
      current nanomedicines.

PMID- 28759197
TI  - Cryogenic Fab-on-a-Chip Sticks the Landing.
AB  - Using a microelectromechanical systems (MEMS)-based Fab-on-a-Chip, we quench
      condense lead thin-films. Suppressing the formation of lead islands makes it
      possible to grow a homogeneous and continuous film as thin as 2 nm, without the
      use of an adhesion layer. Thermal cycling from 3 K to as low as 10 K reveals
      irreversible annealing of the thin-film characteristic of a metastable state. The
      transition to the stable state is smooth and is completed by cycling the
      temperature above ~42 K, where a distinctive resistance minimum is observed. This
      resistive minimum is accompanied by an unexpected peak in the superconducting
      transition temperature. After further thermal cycling, the standard
      metallic/superconductive behavior is established. The MEMS-based approach yields
      a platform for systematic studies of quench-condensed thin-film materials, making
      an intriguing parameter space of mesoscopic physics experimentally accessible.

PMID- 28759195
TI  - Photoacoustic Imaging of Human Mesenchymal Stem Cells Labeled with Prussian Blue
      Poly(l-lysine) Nanocomplexes.
AB  - Acoustic imaging is affordable and accessible without ionizing radiation.
      Photoacoustic imaging increases the contrast of traditional ultrasound and can
      offer good spatial resolution when used at high frequencies with excellent
      temporal resolution. Prussian blue nanoparticles (PBNPs) are an emerging
      photoacoustic contrast agent with strong optical absorption in the near-infrared
      region. In this study, we developed a simple and efficient method to label human
      mesenchymal stem cells (hMSCs) with PBNPs and imaged them with photoacoustic
      imaging. First, PBNPs were synthesized by the reaction of FeCl3 with K4[Fe(CN)6]
      in the presence of citric acid and complexed with the cationic transfection agent
      poly-l-lysine (PLL). The PLL-coated PBNPs (PB-PLL nanocomplexes) have a maximum
      absorption peak at 715 nm and could efficiently label hMSCs. Cellular uptake of
      these nanocomplexes was studied using bright field, fluorescence, and
      transmission electron microscopy. The labeled stem cells were successfully
      differentiated into two downstream lineages of adipocytes and osteocytes, and
      they showed positive expression for surface markers of CD73, CD90, and CD105. No
      changes in viability or proliferation of the labeled cells were observed, and the
      secretome cytokine analysis indicated that the expression levels of 12 different
      proteins were not dysregulated by PBNP labeling. The optical properties of PBNPs
      were preserved postlabeling, suitable for the sensitive and quantitative
      detection of implanted cells. Labeled hMSCs exhibited strong photoacoustic
      contrast in vitro and in vivo when imaged at 730 nm, and the detection limit was
      200 cells/MUL in vivo. The photoacoustic signal increased as a function of cell
      concentration, indicating that the number of labeled cells can be quantified
      during and after cell transplantations. In hybrid ultrasound/photoacoustic
      imaging, this approach offers real-time and image-guided cellular injection even
      through an intact skull for brain intraparenchymal injections. Our labeling and
      imaging technique allowed the detection and monitoring of 5 * 104 mesenchymal
      stem cells in living mice over a period of 14 days.

PMID- 28759198
TI  - Passive and Space-Discriminative Ionic Sensors Based on Durable Nanocomposite
      Electrodes toward Sign Language Recognition.
AB  - This work developed an ionic sensor for human motion monitoring by employing
      durable H-reduced graphene oxide (RGO)/carbon nanotubes (CNTs)/Ag electrodes and
      an ionic polymer interlayer. The sensor functions as a result of unbalanced ion
      transport and accumulation between two electrodes stimulated by applied
      deformation. The networking structure and stable electrodes provide convenient
      ion-transport channels and a large ion accumulation space, resulting in a
      sensitivity of 2.6 mV in the strain range below 1% and high stability over 6000
      bending cycles. Ionic sensors are of intense interest motivated by detecting
      human activities, which usually associate with a large strain or deformation
      change. More importantly, direction identification and spatial deformation
      recognition are feasible in this research, which is beneficial for the detection
      of complex multidimensional activities. Here, an integrated smart glove with
      several sensors mounted on the hand joints displays a distinguished ability in
      the complex geometry of hand configurations. Based on its superior performance,
      the potential applications of this passive ionic sensor in sign language
      recognition and human-computer interaction are demonstrated.

PMID- 28759199
TI  - TiO2-BiVO4 Heterostructure to Enhance Photoelectrochemical Efficiency for
      Sensitive Aptasensing.
AB  - This work designed a nanocomposite to enhance the photoelectrochemical (PEC)
      efficiency by depositing BiVO4 nanoparticles on TiO2 nanospheres with a
      solvothermal method. The TiO2-BiVO4 heterostructure was characterized with
      various spectroscopic and microscopic techniques and was employed as a
      nanostructured support to cross-link DNA aptamer for constructing a visible-light
      driven PEC aptasensor. The TiO2 nanospheres provided a biocompatible
      microenvironment, and the high surface area of the heterostructure enhanced the
      loading of aptamer molecules. The small energy gap of BiVO4 improved the PEC
      property of the nanocomposite compared with the pure TiO2 under visible-light
      irradiation. The advantages of the nanocomposite along with the high loading of
      recognition molecules greatly improved the sensitivity of the aptasensor. Using
      17beta-estradiol as an analyst model, the proposed PEC biosensor showed excellent
      analytical performance with high sensitivity, low detection limit of 0.022 pM,
      and high selectivity in a detectable concentration range of 0.1-250 pM,
      indicating the promising application of the designed TiO2-BiVO4 heterostructure
      in PEC biosensing.

PMID- 28759200
TI  - Control of Elemental Distribution in the Nanoscale Solid-State Reaction That
      Produces (Ga1-xZnx)(N1-xOx) Nanocrystals.
AB  - Solid-state chemical transformations at the nanoscale can be a powerful tool for
      achieving compositional complexity in nanomaterials. It is desirable to
      understand the mechanisms of such reactions and characterize the local-level
      composition of the resulting materials. Here, we examine how reaction temperature
      controls the elemental distribution in (Ga1-xZnx)(N1-xOx) nanocrystals (NCs)
      synthesized via the solid-state nitridation of a mixture of nanoscale ZnO and
      ZnGa2O4 NCs. (Ga1-xZnx)(N1-xOx) is a visible-light absorbing semiconductor that
      is of interest for applications in solar photochemistry. We couple elemental
      mapping using energy-dispersive X-ray spectroscopy in a scanning transmission
      electron microscope (STEM-EDS) with colocation analysis to study the elemental
      distribution and the degree of homogeneity in the (Ga1-xZnx)(N1-xOx) samples
      synthesized at temperatures ranging from 650 to 900  degrees C with varying
      ensemble compositions (i.e., x values). Over this range of temperatures, the
      elemental distribution ranges from highly heterogeneous at 650  degrees C,
      consisting of a mixture of larger particles with Ga and N enrichment near the
      surface and very small NCs, to uniform particles with evenly distributed
      constituent elements for most compositions at 800  degrees C and above. We
      propose a mechanism for the formation of the (Ga1-xZnx)(N1-xOx) NCs in the solid
      state that involves phase transformation of cubic spinel ZnGa2O4 to wurtzite (Ga1
      xZnx)(N1-xOx) and diffusion of the elements along with nitrogen incorporation.
      The temperature-dependence of nitrogen incorporation, bulk diffusion, and vacancy
      assisted diffusion processes determines the elemental distribution at each
      synthesis temperature. Finally, we discuss how the visible band gap of (Ga1
      xZnx)(N1-xOx) NCs varies with composition and elemental distribution.

PMID- 28759201
TI  - Shape Memory Micro- and Nanowire Libraries for the High-Throughput Investigation
      of Scaling Effects.
AB  - The scaling behavior of Ti-Ni-Cu shape memory thin-film micro- and nanowires of
      different geometry is investigated with respect to its influence on the
      martensitic transformation properties. Two processes for the high-throughput
      fabrication of Ti-Ni-Cu micro- to nanoscale thin film wire libraries and the
      subsequent investigation of the transformation properties are reported. The
      libraries are fabricated with compositional and geometrical (wire width)
      variations to investigate the influence of these parameters on the transformation
      properties. Interesting behaviors were observed: Phase transformation
      temperatures change in the range from 1 to 72  degrees C (austenite finish, (Af),
      13 to 66  degrees C (martensite start, Ms) and the thermal hysteresis from -3.5
      to 20 K. It is shown that a vanishing hysteresis can be achieved for special
      combinations of sample geometry and composition.

PMID- 28759202
TI  - In Vivo Toxicity Assessment of Occupational Components of the Carbon Nanotube
      Life Cycle To Provide Context to Potential Health Effects.
AB  - Pulmonary toxicity studies on carbon nanotubes focus primarily on as-produced
      materials and rarely are guided by a life cycle perspective or integration with
      exposure assessment. Understanding toxicity beyond the as-produced, or pure
      native material, is critical, due to modifications needed to overcome barriers to
      commercialization of applications. In the first series of studies, the toxicity
      of as-produced carbon nanotubes and their polymer-coated counterparts was
      evaluated in reference to exposure assessment, material characterization, and
      stability of the polymer coating in biological fluids. The second series of
      studies examined the toxicity of aerosols generated from sanding polymer-coated
      carbon-nanotube-embedded or neat composites. Postproduction modification by
      polymer coating did not enhance pulmonary injury, inflammation, and pathology or
      in vitro genotoxicity of as-produced carbon nanotubes, and for a particular
      coating, toxicity was significantly attenuated. The aerosols generated from
      sanding composites embedded with polymer-coated carbon nanotubes contained no
      evidence of free nanotubes. The percent weight incorporation of polymer-coated
      carbon nanotubes, 0.15% or 3% by mass, and composite matrix utilized altered the
      particle size distribution and, in certain circumstances, influenced acute in
      vivo toxicity. Our study provides perspective that, while the number of workers
      and consumers increases along the life cycle, toxicity and/or potential for
      exposure to the as-produced material may greatly diminish.

PMID- 28759203
TI  - Structural and Functional Characterization of the Histidine Phosphatase Domains
      of Human Sts-1 and Sts-2.
AB  - The suppressor of T cell signaling (Sts) proteins, Sts-1 and Sts-2, are
      homologous phosphatases that negatively regulate signaling pathways downstream of
      the T cell receptor. Functional inactivation of Sts-1 and Sts-2 in a murine model
      leads to resistance to systemic infection by the opportunistic pathogen, Candida
      albicans. This suggests that modulation of the host immune response by inhibiting
      Sts function may be a viable strategy for treating these deadly fungal pathogen
      infections. To better understand the molecular determinants of function and
      structure, we characterized the structure and steady-state kinetics of the
      histidine phosphatase domains of human Sts-1 (Sts-1HP) and Sts-2 (Sts-2HP). We
      determined the X-ray crystal structures of unliganded Sts-1HP and Sts-1HP in
      complex with sulfate to 2.5 and 1.9 A, respectively, and the structure of Sts-2HP
      with sulfate to 2.4 A. The steady-state kinetic analysis shows, as expected, that
      Sts-1HP has a phosphatase activity significantly higher than that of Sts-2HP and
      that the human and mouse proteins behave similarly. In addition, comparison of
      the phosphatase activity of full-length Sts-1 protein to Sts-1HP reveals similar
      kinetics, indicating that Sts-1HP is a functional surrogate for the native
      protein. We also tested known phosphatase inhibitors and determined that the SHP
      1 inhibitor, PHPS1, is a potent inhibitor of Sts-1 (Ki = 1.05 +/- 0.15 MUM).
      Finally, we demonstrated that human Sts-1 has robust phosphatase activity against
      the substrate, Zap-70, in a cell-based assay. Collectively, these data suggest
      that the human Sts proteins are druggable targets and provide a structural basis
      for future drug development efforts.

PMID- 28759205
TI  - Hybrid QM/MM Molecular Dynamics with AMOEBA Polarizable Embedding.
AB  - We present the implementation of a Born-Oppenheimer (BO) hybrid quantum
      mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) strategy using
      density functional theory (DFT) and the polarizable AMOEBA force field. This
      approach couples the Gaussian and Tinker suite of programs through a variational
      formalism allowing for a full self-consistent relaxation of both the AMOEBA
      induced dipoles and the DFT electron density at each MD step. As the DFT SCF
      cycles are the limiting factor in terms of computational efforts and MD
      stability, we focus on the latter aspect and compare the time-reversible BO (TR
      BO) and the extended BO Lagrangian approaches (XL-BO) to the MD propagation. The
      XL-BO approach allows for stable, energy-conserving trajectories offering various
      perspectives for hybrid simulations using polarizable force fields.

PMID- 28759204
TI  - Variation in Extracellular Detoxification Is a Link to Different Carcinogenicity
      among Chromates in Rodent and Human Lungs.
AB  - Inhalation of soluble chromium(VI) is firmly linked with higher risks of lung
      cancer in humans. However, comparative studies in rats have found a high lung
      tumorigenicity for moderately soluble chromates but no tumors for highly soluble
      chromates. These major species differences remain unexplained. We investigated
      the impact of extracellular reducers on responses of human and rat lung
      epithelial cells to different Cr(VI) forms. Extracellular reduction of Cr(VI) is
      a detoxification process, and rat and human lung lining fluids contain different
      concentrations of ascorbate and glutathione. We found that reduction of chromate
      anions in simulated lung fluids was principally driven by ascorbate with only
      minimal contribution from glutathione. The addition of 500 MUM ascorbate (~rat
      lung fluid concentration) to culture media strongly inhibited cellular uptake of
      chromate anions and completely prevented their cytotoxicity even at otherwise
      lethal doses. While proportionally less effective, 50 MUM extracellular ascorbate
      (~human lung fluid concentration) also decreased uptake of chromate anions and
      their cytotoxicity. In comparison to chromate anions, uptake and cytotoxicity of
      respirable particles of moderately soluble CaCrO4 and SrCrO4 were much less
      sensitive to suppression by extracellular ascorbate, especially during early
      exposure times and in primary bronchial cells. In the absence of extracellular
      ascorbate, chromate anions and CaCrO4/SrCrO4 particles produced overall similar
      levels of DNA double-stranded breaks, with less soluble particles exhibiting a
      slower rate of breakage. Our results indicate that a gradual extracellular
      dissolution and a rapid internalization of calcium chromate and strontium
      chromate particles makes them resistant to detoxification outside the cells,
      which is extremely effective for chromate anions in the rat lung fluid. The
      detoxification potential of the human lung fluid is significant but much lower
      and insufficient to provide a threshold-type dose dependence for soluble
      chromates.

PMID- 28759206
TI  - Electronic Effect of Ruthenium Nanoparticles on Efficient Reductive Amination of
      Carbonyl Compounds.
AB  - Highly selective synthesis of primary amines over heterogeneous catalysts is
      still a challenge for the chemical industry. Ruthenium nanoparticles supported on
      Nb2O5 act as a highly selective and reusable heterogeneous catalyst for the low
      temperature reductive amination of various carbonyl compounds that contain
      reduction-sensitive functional groups such as heterocycles and halogens with NH3
      and H2 and prevent the formation of secondary amines and undesired hydrogenated
      byproducts. The selective catalysis of these materials is likely attributable to
      the weak electron-donating capability of Ru particles on the Nb2O5 surface. The
      combination of this catalyst and homogeneous Ru systems was used to synthesize
      2,5-bis(aminomethyl)furan, a monomer for aramid production, from 5
      (hydroxymethyl)furfural without a complex mixture of imine byproducts.

PMID- 28759207
TI  - Prolonged Exposure to Bisphenol A from Single Dermal Contact Events.
AB  - Bisphenol A (BPA) is an endocrine disruptor frequently detected in human
      biofluids. Dermal absorption of BPA from thermal paper receipts occurs but BPA
      pharmacokinetics following dermal exposure is not understood. To compare the
      pharmacokinetics of dermal and dietary BPA exposure, six male participants
      handled simulated receipts containing relevant levels of BPA (isotope-labeled BPA
      d16) for 5 min, followed by hand-washing 2 h later. Urine (0-48 h) and serum (0
      7.5 h) were monitored for free and total BPA-d16. One week later, participants
      returned for a dietary administration with monitoring as above. One participant
      repeated the dermal administration with extended monitoring of urine (9 days) and
      serum (2 days). After dietary exposure, urine total BPA-d16 peaked within 5 h and
      quickly cleared within 24 h. After dermal exposure, cumulative excretion
      increased linearly for 2 days, and half the participants still had detectable
      urinary total BPA-d16 after 1 week. The participant repeating the dermal exposure
      had detectable BPA-d16 in urine for 9 days, showed linear cumulative excretion
      over 5 days, and had detectable free BPA-d16 in serum. Proportions of free BPA
      d16 in urine following dermal exposure (0.71%-8.3% of total BPA-d16) were
      generally higher than following the dietary exposure (0.29%-1.4%). Compared to
      dietary BPA exposure, dermal absorption of BPA leads to prolonged exposure and
      may lead to higher proportions of unconjugated BPA in systemic circulation.

PMID- 28759208
TI  - Correction to Purification-Free Method for Preparing Technetium-99m-Labeled
      Multivalent Probes for Enhanced in Vivo Imaging of Saturable Systems.

PMID- 28759209
TI  - Metal (Hydr)oxides@Polymer Core-Shell Strategy to Metal Single-Atom Materials.
AB  - Preparing metal single-atom materials is currently attracting tremendous
      attention and remains a significant challenge. Herein, we report a novel core
      shell strategy to synthesize single-atom materials. In this strategy, metal
      hydroxides or oxides are coated with polymers, followed by high-temperature
      pyrolysis and acid leaching, metal single atoms are anchored on the inner wall of
      hollow nitrogen-doped carbon (CN) materials. By changing metal precursors or
      polymers, we demonstrate the successful synthesis of different metal single atoms
      dispersed on CN materials (SA-M/CN, M = Fe, Co, Ni, Mn, FeCo, FeNi, etc.).
      Interestingly, the obtained SA-Fe/CN exhibits much higher catalytic activity for
      hydroxylation of benzene to phenol than Fe nanoparticles/CN (45% vs 5% benzene
      conversion). First-principle calculations further reveal that the high reactivity
      originates from the easier formation of activated oxygen species at the single Fe
      site. Our methodology provides a convenient route to prepare a variety of metal
      single-atom materials representing a new class of catalysts.

PMID- 28759210
TI  - Effective Conformational Sampling in Explicit Solvent with Gaussian Biased
      Accelerated Molecular Dynamics.
AB  - In this Article, a user-friendly Gaussian biased accelerated molecular dynamics
      (GbAMD) method is presented that uses a sum of Gaussians of potential energies as
      the biased force to accelerate the conformational sampling. The easy parameter
      setting of GbAMD is demonstrated in a variety of simulation tests for the
      conformational transitions of proteins with various complexity including the
      folding of Trpcage, GB1p, and HP35 peptides as well as the functional
      conformational changes of nCaM and HIV-1 PR proteins. Additionally, the ability
      of GbAMD in conformational sampling and free-energy evaluation is quantitatively
      assessed through the comparison of GbAMD simulations on the folding of alpha
      helical Trpcage and beta-hairpin GB1p with the accompanying standard dual boost
      AMD and conventional MD (cMD) simulations. While GbAMD can fold both peptides
      into their native structures repeatedly in individual trajectories, AMD can only
      fold Trpcage and cMD fails the folding in both cases. As a result, only GbAMD can
      quantitatively measure the properties of the equilibrium conformational ensemble
      of protein folding consistent with experimental data. Also notable is that the
      structural properties of the indispensable unfolded and transition states in the
      folding pathways of Trpcage and GB1p characterized by GbAMD simulations are in
      great agreement with previous simulations on the two peptides. In summary, GbAMD
      has an effective conformational sampling ability that provides a convenient and
      effective access for simulating the structural dynamics of biomolecular systems.

PMID- 28759211
TI  - Behavior of Zein in Aqueous Ethanol under Atmospheric Pressure Cold Plasma
      Treatment.
AB  - The effects of atmospheric cold plasma (ACP) on zein in aqueous ethanol (80%,
      v/v) were investigated including particle size distribution, molecular structure,
      and content of free sulfhydryl (free-SH) group and disulfide bond, etc. The film
      forming properties of zein films were also characterized. After ACP treatment,
      the particle size of zein aggregates showed a remarkable decrease and uniform
      particle distribution. There was a downward trend both in pH value and viscosity
      with the increasing ACP treatment intensity. Moreover, the increase of disulfide
      bonds concentration was suggested to be correlated to the compact structure
      strengthened by cross-linking between zein molecules. It was proved from SEM
      micrographs that plasma could significantly decrease the aggregation degree of
      zein micelles. There was a slight decrease of the peak intensity in UV and
      fluorescence spectra compared with native zein, indicating the bulk structure of
      zein solution had not been disrupted. The reinforced flexibility and tensile
      strength of zein films had been observed after treatment on film-forming
      solution. This study provided an experimental basis for the investigation on
      behavior of plasma-treated protein in solution.

PMID- 28759212
TI  - Targeted Protein Detection Using an All-in-One Mass Spectrometry Cartridge.
AB  - We developed a simple 3D printed cartridge for mass spectrometry (MS) targeted
      detection of plasma proteins, including post-translational modifications (PTMs).
      The cartridge uses an integrated antibody enrichment column to preconcentrate the
      protein target as well as a novel built-in substrate to ionize the protein
      targets for MS detection. We show several examples of using this cartridge to
      perform rapid detection of clinically significant proteoforms from plasma
      samples.

PMID- 28759214
TI  - [MoS4]2- Cluster Bridges in Co-Fe Layered Double Hydroxides for Mercury Uptake
      from S-Hg Mixed Flue Gas.
AB  - [MoS4]2- clusters were bridged between CoFe layered double hydroxide (LDH) layers
      using the ion-exchange method. [MoS4]2-/CoFe-LDH showed excellent Hg0 removal
      performance under low and high concentrations of SO2, highlighting the potential
      for such material in S-Hg mixed flue gas purification. The maximum mercury
      capacity was as high as 16.39 mg/g. The structure and physical-chemical
      properties of [MoS4]2-/CoFe-LDH composites were characterized with FT-IR, XRD,
      TEM&SEM, XPS, and H2-TPR. [MoS4]2- clusters intercalated into the CoFe-LDH
      layered sheets; then, we enlarged the layer-to-layer spacing (from 0.622 to 0.880
      nm) and enlarged the surface area (from 41.4 m2/g to 112.1 m2/g) of the
      composite. During the adsorption process, the interlayer [MoS4]2- cluster was the
      primary active site for mercury uptake. The adsorbed mercury existed as HgS on
      the material surface. The absence of active oxygen results in a composite with
      high sulfur resistance. Due to its high efficiency and SO2 resistance, [MoS4]2
      /CoFe-LDH is a promising adsorbent for mercury uptake from S-Hg mixed flue gas.

PMID- 28759213
TI  - Design and Evolution of a Macrocyclic Peptide Inhibitor of the Sonic
      Hedgehog/Patched Interaction.
AB  - The hedgehog (Hh) signaling pathway plays a central role during embryonic
      development, and its aberrant activation has been implicated in the development
      and progression of several human cancers. Major efforts toward the identification
      of chemical modulators of the hedgehog pathway have yielded several antagonists
      of the GPCR-like smoothened receptor. In contrast, potent inhibitors of the sonic
      hedgehog/patched interaction, the most upstream event in ligand-induced
      activation of this signaling pathway, have been elusive. To address this gap, a
      genetically encoded cyclic peptide was designed based on the sonic hedgehog (Shh)
      binding loop of hedgehog-interacting protein (HHIP) and subjected to multiple
      rounds of affinity maturation through the screening of macrocyclic peptide
      libraries produced in E. coli cells. Using this approach, an optimized
      macrocyclic peptide inhibitor (HL2-m5) was obtained that binds Shh with a KD of
      170 nM, which corresponds to a 120-fold affinity improvement compared to the
      parent molecule. Importantly, HL2-m5 is able to effectively suppress Shh-mediated
      hedgehog signaling and Gli-controlled gene transcription in living cells (IC50 =
      230 nM), providing the most potent inhibitor of the sonic hedgehog/patched
      interaction reported to date. This first-in-class macrocyclic peptide modulator
      of the hedgehog pathway is expected to provide a valuable probe for investigating
      and targeting ligand-dependent hedgehog pathway activation in cancer and other
      pathologies. This work also introduces a general strategy for the development of
      cyclopeptide inhibitors of protein-protein interactions.

PMID- 28759215
TI  - Discovery of a para-Acetoxy-benzyl Ester Prodrug of a Hydroxamate-Based Glutamate
      Carboxypeptidase II Inhibitor as Oral Therapy for Neuropathic Pain.
AB  - 4-Carboxy-alpha-[3-(hydroxyamino)-3-oxopropyl]-benzenepropanoic acid 1 is a
      potent hydroxamate-based inhibitor of glutamate carboxypeptidase II. In an
      attempt to improve its poor oral pharmacokinetics, we synthesized a series of
      prodrugs by masking its hydrophilic hydroxamate group. Prodrugs were evaluated
      for oral availability in mice and showed varying degree of plasma exposure to 1.
      Of these, para-acetoxybenzyl-based, 4-(5-(((4-acetoxybenzyl)oxy)amino)-2-carboxy
      5-oxopentyl)benzoic acid, 12, provided 5-fold higher plasma levels of 1 compared
      to oral administration of 1 itself. Subsequently, para-acetoxybenzyl-based
      prodrugs with additional ester promoiety(ies) on carboxylate(s) were examined for
      their ability to deliver 1 to plasma. Isopropyloxycarbonyloxymethyl (POC) ester
      30 was the only prodrug that achieved substantial plasma levels of 1. In vitro
      metabolite identification studies confirmed stability of the ethyl ester of
      benzoate while the POC group was rapidly hydrolyzed. At oral daily dose
      equivalent of 3 mg/kg, 12 exhibited analgesic efficacy comparable to dose of 10
      mg/kg of 1 in the rat chronic constrictive injury model of neuropathic pain.

PMID- 28759216
TI  - Allosteric Inhibitors, Crystallography, and Comparative Analysis Reveal Network
      of Coordinated Movement across Human Herpesvirus Proteases.
AB  - Targeting of cryptic binding sites represents an attractive but underexplored
      approach to modulating protein function with small molecules. Using the dimeric
      protease (Pr) from Kaposi's sarcoma-associated herpesvirus (KSHV) as a model
      system, we sought to dissect a putative allosteric network linking a cryptic site
      at the dimerization interface to enzyme function. Five cryogenic X-ray structures
      were solved of the monomeric protease with allosteric inhibitors bound to the
      dimer interface site. Distinct coordinated movements captured by the allosteric
      inhibitors were also revealed as alternative states in room-temperature X-ray
      data and comparative analyses of other dimeric herpesvirus proteases. A two-step
      mechanism was elucidated through detailed kinetic analyses and suggests an enzyme
      isomerization model of inhibition. Finally, a representative allosteric inhibitor
      from this class was shown to be efficacious in a cellular model of viral
      infectivity. These studies reveal a coordinated dynamic network of atomic
      communication linking cryptic binding site occupancy and allosteric inactivation
      of KHSV Pr that can be exploited to target other members of this clinically
      relevant family of enzymes.

PMID- 28759217
TI  - Chitosan and Laminarin as Alternatives to Copper for Plasmopara viticola Control:
      Effect on Grape Amino Acid.
AB  - Copper fungicide use is limited by the European regulation; therefore, new
      strategies have been developed to prevent grapevine downy mildew (GDM). However,
      there is poor information about their effects on grape amino acid composition.
      This field trial aimed to evaluate the effect on grape amino acid composition of
      chitosan and of a mixture of laminarin and Saccharomyces extracts (LamE), applied
      in different strategies with copper hydroxide. The results showed that all the
      treatments applied to grapevines decreased the concentration of several amino
      acids. Moreover, treatments that have mostly decreased these compounds are those
      with copper hydroxide, especially when applied individually. LamE applied
      individually or alternately with copper hydroxide had the least negative effect
      on grape amino acid content. These results provide further information about the
      negative effects of copper on grape quality, which can be reduced when it is used
      in strategy with LamE or chitosan in GDM control.

PMID- 28759218
TI  - Uranium(IV) Chloride Complexes: UCl62- and an Unprecedented U(H2O)4Cl4 Structural
      Unit.
AB  - The room temperature synthesis and structural characterization of two U(IV)
      compounds isolated from acidic aqueous solution is reported. Evaporation of a
      U(IV)/HCl solution containing pyridinium (HPy) yielded (HPy)2UCl6 (1), yet in the
      presence of an organic carboxylate U(H2O)4Cl4.(HPy.Cl)2 (2) is obtained. The
      structures have been determined by single crystal X-ray diffraction and
      characterized by Raman, IR, and optical spectroscopies. The magnetism of both
      compounds was also investigated. The structure of 1 is built from UCl62- anionic
      units, pervasive in descriptions of the aqueous chemistry of tetravalent uranium,
      and is found to undergo a phase transition from C2/m to P1 upon cooling. By
      comparison, the structure of 2 contains a neutral U(IV)-aquo-chloro complex,
      U(H2O)4Cl4, for which there is no literature precedence. Density functional
      theory calculations were performed to predict the geometries, vibrational
      frequencies, and relative energetics of the UCl62- and U(H2O)4Cl4 units. The
      energetics of the reaction of U(H2O)4Cl4 to form the dianion are predicted to be
      exothermic in the gas phase and in aqueous solution. The predicted energetics
      coupled with no previous solid state reports of a U(IV)-aquo-chloro complex may
      point toward the importance of hydrogen bonding and other supramolecular
      interactions, prevalent in the structures of 1 and 2, on the stabilization and/or
      crystallization of the U(H2O)4Cl4 structural unit.

PMID- 28759219
TI  - Synthesis and Characterization of Luminescent Cyclometalated Platinum(II)
      Complexes with Tunable Emissive Colors and Studies of Their Application in
      Organic Memories and Organic Light-Emitting Devices.
AB  - A series of luminescent cyclometalated N^C^N [N^C^N = 1,3-bis(N-alkylbenzimidazol
      2'-yl)benzene]platinum(II) alkynyl and carbazolyl complexes has been prepared.
      The structure of one platinum(II) carbazolyl complex has been characterized by X
      ray crystallography. The corresponding electrochemical and photophysical
      properties have been explored and analyzed. The N^C^N platinum(II) complexes
      displayed rich luminescence in degassed dichloromethane solution, with their
      emission profiles dependent on the coordinated alkynyl and carbazolyl ligands.
      Their emission energies are correlated to the electronic properties of the
      alkynyl and carbazolyl ligands. By varying the electronic properties of the
      alkynyl and carbazolyl ligands, emission energies could be fine-tuned to cover a
      wide range of the visible spectrum, as supported by computational studies. A
      donor-acceptor platinum(II) complex has been utilized to fabricate memory devices
      that exhibit binary memory performances with low operating voltages, high ON/OFF
      ratios, and long retention times. Solution-processable OLEDs have been fabricated
      based on another platinum(II) carbazolyl complex, resulting in a maximum external
      quantum efficiency of up to 7.2%, which is comparable to that of the vacuum
      deposited devices based on the small-molecule counterpart, illustrating the
      multifunctional nature of the platinum(II)-containing materials.

PMID- 28759220
TI  - N-Heterocyclic Carbene-Stabilized Boranthrene as a Metal-Free Platform for the
      Activation of Small Molecules.
AB  - The multielectron reduction of small molecules (e.g., CO2) is a key aspect of
      fuel synthesis from renewable electricity. Transition metals have been researched
      extensively in this role due to their intrinsic redox properties and reactivity,
      but more recently, strategies that forego transition metal ions for p-block
      elements have emerged. In this vein, we report an analogue of boranthrene (9,10
      diboraanthracene) stabilized by N-heterocyclic carbenes and its one- and two
      electron oxidized congeners. This platform exhibits reversible, two-electron
      redox chemistry at mild potentials and reacts with O2, CO2, and ethylene via
      formal [4+2] cycloaddition to the central diborabutadiene core. In an area
      traditionally dominated by transition metals, these results outline an approach
      for the redox activation of small molecules at mild potentials based on
      conjugated, light element scaffolds.

PMID- 28759221
TI  - Nucleophilic Aromatic Addition in Ionizing Environments: Observation and Analysis
      of New C-N Valence Bonds in Complexes between Naphthalene Radical Cation and
      Pyridine.
AB  - Radical organic ions can be stabilized by complexation with neutral organics via
      interactions that can resemble chemical bonds, but with much diminished bond
      energies. Those interactions are a key factor in cluster growth and
      polymerization reactions in ionizing environments such as regions of the
      interstellar medium and solar nebulae. Such radical cation complexes between
      naphthalene (Naph) and pyridine (Pyr) are characterized using mass-selected ion
      mobility experiments. The measured enthalpy of binding of the Naph+*(Pyr)
      heterodimer (20.9 kcal/mol) exceeds that of the Naph+*(Naph) homodimer (17.8
      kcal/mol). The addition of 1-3 more pyridine molecules to the Naph+*(Pyr)
      heterodimer gives 10-11 kcal/mol increments in binding enthalpy. A rich array of
      Naph+*(Pyr) isomers are characterized by electronic structure calculations. The
      calculated Boltzmann distribution at 400 K yields an enthalpy of binding in
      reasonable agreement with experiment. The global minimum is a distonic cation
      formed by Pyr attack on Naph+* at the alpha-carbon, changing its hybridization
      from sp2 to distorted sp3. The measured collision cross section in helium for the
      Naph+*(Pyr) heterodimer of 84.9 +/- 2.5 A2 at 302 K agrees well with calculated
      angle-averaged cross sections (83.9-85.1 A2 at 302 K) of the lowest energy
      distonic structures. A remarkable 16 kcal/mol increase in the binding energy
      between Naph+*(Pyr) and Bz+*(Pyr) (Bz is benzene) is understood by energy
      decomposition analysis. A similar increase in binding from Naph+*(NH3) to
      Naph+*(Pyr) (as well as between Bz+*(NH3) and Bz+*(Pyr)) is likewise
      rationalized.

PMID- 28759222
TI  - A Permeability-Limited Physiologically Based Pharmacokinetic (PBPK) Model for
      Perfluorooctanoic acid (PFOA) in Male Rats.
AB  - Physiologically based pharmacokinetic (PBPK) modeling is a powerful in silico
      tool that can be used to simulate the toxicokinetics and tissue distribution of
      xenobiotic substances, such as perfluorooctanoic acid (PFOA), in organisms.
      However, most existing PBPK models have been based on the flow-limited assumption
      and largely rely on in vivo data for parametrization. In this study, we propose a
      permeability-limited PBPK model to estimate the toxicokinetics and tissue
      distribution of PFOA in male rats. Our model considers the cellular uptake and
      efflux of PFOA via both passive diffusion and transport facilitated by various
      membrane transporters, association with serum albumin in circulatory and
      extracellular spaces, and association with intracellular proteins in liver and
      kidney. Model performance is assessed using seven experimental data sets
      extracted from three different studies. Comparing model predictions with these
      experimental data, our model successfully predicts the toxicokinetics and tissue
      distribution of PFOA in rats following exposure via both IV and oral routes. More
      importantly, rather than requiring in vivo data fitting, all PFOA-related
      parameters were obtained from in vitro assays. Our model thus provides an
      effective framework to test in vitro-in vivo extrapolation and holds great
      promise for predicting toxicokinetics of per- and polyfluorinated alkyl
      substances in humans.

PMID- 28759223
TI  - Harnessing Molecular Photon Upconversion in a Solar Cell at Sub-solar Irradiance:
      Role of the Redox Mediator.
AB  - Self-assembled bilayers offer a promising strategy to directly harness photon
      upconversion via triplet-triplet annihilation (TTA-UC) and increase maximum
      theoretical solar cell efficiencies from 33% to >43%. Here we demonstrate that
      the choice of redox mediator in these solar cells has a profound influence on
      both the light harvesting and TTA-UC efficiency. Devices with CoII/III(phen)3 as
      the redox mediator produced the highest photocurrent yet generated from TTA-UC
      (0.158 mA cm-2) under 1 sun. Despite generating less photocurrent, CoII/III(pz-py
      pz)2 devices achieved maximum TTA-UC efficiency at excitation intensities well
      below solar irradiance (0.8 mW cm-2), which is on par with the lowest value yet
      reported for any TTA-UC system. The large variation in performance with respect
      to mediator is attributed to triplet excited-state quenching via (1) energy
      transfer or paramagnetic quenching by the CoII species and (2) excited-state
      electron transfer to CoIII species.

PMID- 28759225
TI  - Determination of Glyphosate, Maleic Hydrazide, Fosetyl Aluminum, and Ethephon in
      Grapes by Liquid Chromatography/Tandem Mass Spectrometry.
AB  - A simple high-throughput liquid chromatography/tandem mass spectrometry (LC-MS
      MS) method was developed for the determination of maleic hydrazide, glyphosate,
      fosetyl aluminum, and ethephon in grapes using a reversed-phase column with weak
      anion-exchange and cation-exchange mixed mode. A 5 g test portion was shaken with
      50 mM HOAc and 10 mM Na2EDTA in 1/3 (v/v) MeOH/H2O for 10 min. After
      centrifugation, the extract was passed through an Oasis HLB cartridge to retain
      suspended particulates and nonpolar interferences. The final solution was
      injected and directly analyzed in 17 min by LC-MS-MS. Two MS-MS transitions were
      monitored in the method for each target compound to achieve true positive
      identification. Four isotopically labeled internal standards corresponding to
      each analyte were used to correct for matrix suppression effects and/or
      instrument signal drift. The linearity of the detector response was demonstrated
      in the range from 10 to 1000 ng/mL for each analyte with a coefficient of
      determination (R2) of >=0.995. The average recovery for all analytes at 100, 500,
      and 2000 ng/g (n = 5) ranged from 87 to 111%, with a relative standard deviation
      of less than 17%. The estimated LOQs for maleic hydrazide, glyphosate, fosetyl
      Al, and ethephon were 38, 19, 29, and 34 ng/g, respectively.

PMID- 28759226
TI  - Method for Highly Enantioselective Ligation of Two Chiral C(sp3) Stereocenters.
AB  - A method is described for the joining of two alpha-lithiated C(sp3) stereocenters
      efficiently and with retention of configuration. The key step involves the
      effective removal of two electrons from a chiral organocuprate R2CuLi, by i
      propyl 2,4-dinitrobenzoate to form a Cu(III) complex that undergoes at -90 
      degrees C accelerated reductive elimination enantioselectively and exclusively
      without the formation of free radicals.

PMID- 28759224
TI  - N-(Pivaloyloxy)alkoxy-carbonyl Prodrugs of the Glutamine Antagonist 6-Diazo-5-oxo
      l-norleucine (DON) as a Potential Treatment for HIV Associated Neurocognitive
      Disorders.
AB  - Aberrant excitatory neurotransmission associated with overproduction of glutamate
      has been implicated in the development of HIV-associated neurocognitive disorders
      (HAND). The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON, 14) attenuates
      glutamate synthesis in HIV-infected microglia/macrophages, offering therapeutic
      potential for HAND. We show that 14 prevents manifestation of spatial memory
      deficits in chimeric EcoHIV-infected mice, a model of HAND. 14 is not clinically
      available, however, because its development was hampered by peripheral
      toxicities. We describe the synthesis of several substituted N
      (pivaloyloxy)alkoxy-carbonyl prodrugs of 14 designed to circulate inert in plasma
      and be taken up and biotransformed to 14 in the brain. The lead prodrug,
      isopropyl 6-diazo-5-oxo-2-(((phenyl(pivaloyloxy)methoxy)carbonyl)amino)hexanoate
      (13d), was stable in swine and human plasma but liberated 14 in swine brain
      homogenate. When dosed systemically in swine, 13d provided a 15-fold enhanced CSF
      to-plasma ratio and a 9-fold enhanced brain-to-plasma ratio relative to 14,
      opening a possible clinical path for the treatment of HAND.

PMID- 28759227
TI  - Molecular Chemistry of Atmospheric Brown Carbon Inferred from a Nationwide
      Biomass Burning Event.
AB  - Lag Ba'Omer, a nationwide bonfire festival in Israel, was chosen as a case study
      to investigate the influence of a major biomass burning event on the light
      absorption properties of atmospheric brown carbon (BrC). The chemical composition
      and optical properties of BrC chromophores were investigated using a high
      performance liquid chromatography (HPLC) platform coupled to photo diode array
      (PDA) and high resolution mass spectrometry (HRMS) detectors. Substantial
      increase of BrC light absorption coefficient was observed during the night-long
      biomass burning event. Most chromophores observed during the event were
      attributed to nitroaromatic compounds (NAC), comprising 28 elemental formulas of
      at least 63 structural isomers. The NAC, in combination, accounted for 50-80% of
      the total visible light absorption (>400 nm) by solvent extractable BrC. The
      results highlight that NAC, in particular nitrophenols, are important light
      absorption contributors of biomass burning organic aerosol (BBOA), suggesting
      that night time chemistry of *NO3 and N2O5 with particles may play a significant
      role in atmospheric transformations of BrC. Nitrophenols and related compounds
      were especially important chromophores of BBOA. The absorption spectra of the BrC
      chromophores are influenced by the extraction solvent and solution pH, implying
      that the aerosol acidity is an important factor controlling the light absorption
      properties of BrC.

PMID- 28759228
TI  - Discovery of an Orally Bioavailable, Brain-Penetrating, in Vivo Active
      Phosphodiesterase 2A Inhibitor Lead Series for the Treatment of Cognitive
      Disorders.
AB  - Herein, we describe the discovery of a potent, selective, brain-penetrating, in
      vivo active phosphodiesterase (PDE) 2A inhibitor lead series. To identify high
      quality leads suitable for optimization and enable validation of the
      physiological function of PDE2A in vivo, structural modifications of the high
      throughput screening hit 18 were performed. Our lead generation efforts revealed
      three key potency-enhancing functionalities with minimal increases in molecular
      weight (MW) and no change in topological polar surface area (TPSA). Combining
      these structural elements led to the identification of 6-methyl-N-((1R)-1-(4
      (trifluoromethoxy)phenyl)propyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (38a), a
      molecule with the desired balance of preclinical properties. Further
      characterization by cocrystal structure analysis of 38a bound to PDE2A uncovered
      a unique binding mode and provided insights into its observed potency and PDE
      selectivity. Compound 38a significantly elevated 3',5'-cyclic guanosine
      monophosphate (cGMP) levels in mouse brain following oral administration, thus
      validating this compound as a useful pharmacological tool and an attractive lead
      for future optimization.

PMID- 28759229
TI  - Inactivation of Ascaris Eggs in Human Fecal Material Through In Situ Production
      of Carboxylic Acids.
AB  - Discovering new ways to inactivate pathogens in human waste is critical for the
      improvement of worldwide access to sanitation and for the reduction of the
      environmental impact of conventional waste treatment processes. Here, we utilized
      the carboxylate platform and chain elongation to produce n-butyric acid and n
      caproic acid via the anaerobic fermentation of human fecal material. Then, we
      inactivated Ascaris eggs through exposure to these carboxylic acids. Using batch
      experiments with human fecal material as substrate, we accumulated n-butyric acid
      and n-caproic acid at total concentrations (uncharged acid plus conjugate base)
      of 257 and 27.1 mM, respectively. We then showed that carboxylic acids at these
      concentrations inactivated Ascaris eggs when the pH was below the pKa for the
      acids, causing them to exist primarily in the uncharged forms. We observed that
      uncharged carboxylic acids affected viability rather than the pH itself or
      conjugate bases. In addition, we modeled the viability of Ascaris eggs as a
      function of uncharged carboxylic acid concentration for n-butyric acid and n
      caproic acid at exposure times of 2, 6, 12, and 20 days. The results presented
      here indicate that in situ biological production of carboxylic acids in HFM
      provides a promising method of pathogen inactivation and may lead to new
      developments in sanitation technology and treatment of fecal sludge.

PMID- 28759230
TI  - Targeting Unoccupied Surfaces on Protein-Protein Interfaces.
AB  - The use of peptidomimetic scaffolds to target protein-protein interfaces is a
      promising strategy for inhibitor design. The strategy relies on mimicry of
      protein motifs that exhibit a concentration of native hot spot residues. To
      address this constraint, we present a pocket-centric computational design
      strategy guided by AlphaSpace to identify high-quality pockets near the
      peptidomimetic motif that are both targetable and unoccupied. Alpha-clusters
      serve as a spatial representation of pocket space and are used to guide the
      selection of natural and non-natural amino acid mutations to design inhibitors
      that optimize pocket occupation across the interface. We tested the strategy
      against a challenging protein-protein interaction target, KIX/MLL, by optimizing
      a single helical motif within MLL to compete against the full-length wild-type
      MLL sequence. Molecular dynamics simulation and experimental fluorescence
      polarization assays are used to verify the efficacy of the optimized peptide
      sequence.

PMID- 28759232
TI  - Effect of Concentration on the Supramolecular Polymerization Mechanism via
      Implicit-Solvent Coarse-Grained Simulations of Water-Soluble 1,3,5
      Benzenetricarboxamide.
AB  - We report an implicit-solvent coarse-grained (CG) model for a water-soluble 1,3,5
      benzenetricarboxamide (BTA) supramolecular polymer. The technical advances
      guaranteed by this CG model allow simulation of the self-assembly of 1000 BTA
      monomers and easy variation of the BTA concentration into the system down to
      experimental dilute conditions. In this way, we can monitor the mechanism of
      supramolecular polymerization as a function of the concentration at submolecular
      resolution exceeding the microsecond time scale. While increasing the
      concentration produces rapid formation of large disordered clusters that are then
      converted into BTA fibers, moving to very dilute concentrations favors early
      ordering of the oligomers in solution even at small sizes. Interestingly, we
      observe that below a certain concentration the oligomers that dynamically grow in
      solution during the self-assembly present the same level (and amplification) of
      order of prestacked equilibrated oligomers of the same size, meaning that
      concentration-dependent kinetic effects have disappeared from the polymerization
      mechanism.

PMID- 28759231
TI  - Discovery of Novel and Highly Selective Inhibitors of Calpain for the Treatment
      of Alzheimer's Disease: 2-(3-Phenyl-1H-pyrazol-1-yl)-nicotinamides.
AB  - Calpain overactivation has been implicated in a variety of pathological disorders
      including ischemia/reperfusion injury, cataract formation, and neurodegenerative
      diseases such as Alzheimer's disease (AD). Herein we describe our efforts leading
      to the identification of ketoamide-based 2-(3-phenyl-1H-pyrazol-1
      yl)nicotinamides as potent and reversible inhibitors of calpain with high
      selectivity versus related cysteine protease cathepsins, other proteases, and
      receptors. Broad efficacy in a set of preclinical models relevant to AD suggests
      that inhibition of calpain represents an attractive approach with potential
      benefit for the treatment of AD.

PMID- 28759233
TI  - Quasi-Phase Diagrams at Air/Oil Interfaces and Bulk Oil Phases for
      Crystallization of Small-Molecular Semiconductors by Adjusting Gibbs Adsorption.
AB  - The temperature and concentration dependencies of the crystallization of two
      small-molecular semiconductors were clarified by constructing quasi-phase
      diagrams at air/oil interfaces and in bulk oil phases. A quinoidal
      quaterthiophene derivative with four alkyl chains (QQT(CN)4) in 1,1,2,2
      tetrachroloethane (TCE) and a thienoacene derivative with two alkyl chains (C8
      BTBT) in o-dichlorobenzene were used. The apparent crystal nucleation temperature
      (Tn) and dissolution temperature (Td) of the molecules were determined based on
      optical microscopy examination in closed glass capillaries and open dishes during
      slow cooling and heating processes, respectively. Tn and Td were considered
      estimates of the critical temperatures for nuclear formation and crystal growth,
      respectively. The Tn values of QQT(CN)4 and C8-BTBT at the air/oil interfaces
      were higher than those in the bulk oil phases, whereas the Td values at the
      air/oil interfaces were almost the same as those in the bulk oil phases. These
      Gibbs adsorption phenomena were attributed to the solvophobic effect of the alkyl
      chain moieties. The temperature range between Tn and Td corresponds to suitable
      supercooling conditions for ideal crystal growth based on the suppression of
      nucleation. The Tn values at the water/oil and oil/glass interfaces did not shift
      compared with those of the bulk phases, indicating that adsorption did not occur
      at the hydrophilic interfaces. Promotion and inhibition of nuclear formation for
      crystal growth of the semiconductors were achieved at the air/oil and hydrophilic
      interfaces, respectively.

PMID- 28759234
TI  - Synthesis of Pyridylanthracenes and Their Reversible Reaction with Singlet Oxygen
      to Endoperoxides.
AB  - The ortho, meta, and para isomers of 9,10-dipyridylanthracene 1 have been
      synthesized and converted into their endoperoxides 1-O2 upon oxidation with
      singlet oxygen. The kinetics of this reaction can be controlled by the
      substitution pattern and the solvent: in highly polar solvents, the meta isomer
      is the most reactive, whereas the ortho isomer is oxidized fastest in nonpolar
      solvents. Heating of the endoperoxides affords the parent anthracenes by release
      of singlet oxygen.

PMID- 28759235
TI  - Block and Gradient Copoly(2-oxazoline) Micelles: Strikingly Different on the
      Inside.
AB  - Herein, we provide a direct proof for differences in the micellar structure of
      amphiphilic diblock and gradient copolymers, thereby unambiguously demonstrating
      the influence of monomer distribution along the polymer chains on the
      micellization behavior. The internal structure of amphiphilic block and gradient
      co poly(2-oxazolines) based on the hydrophilic poly(2-methyl-2-oxazoline) (PMeOx)
      and the hydrophobic poly(2-phenyl-2-oxazoline) (PPhOx) was studied in water and
      water-ethanol mixtures by small-angle X-ray scattering (SAXS), small-angle
      neutron scattering (SANS), static and dynamic light scattering (SLS/DLS), and 1H
      NMR spectroscopy. Contrast matching SANS experiments revealed that block
      copolymers form micelles with a uniform density profile of the core. In contrast
      to popular assumption, the outer part of the core of the gradient copolymer
      micelles has a distinctly higher density than the middle of the core. We
      attribute the latter finding to back-folding of chains resulting from hydrophilic
      hydrophobic interactions, leading to a new type of micelles that we refer to as
      micelles with a "bitterball-core" structure.

PMID- 28759236
TI  - Electron Donor-Acceptor Nature of the Ethanol-CO2 Dimer.
AB  - Supercritical CO2 is an appealing nontoxic, environmentally friendly solvent for
      the industrial extraction of many classes of compounds, from caffeine to natural
      product drug precursors to petrochemical impurities. Apolar in isolation, the
      ability of supercritical CO2 to dissolve polar species has been empirically shown
      to be greatly enhanced by the addition of a small molar percentage of a polar
      cosolvent, often ethanol. Computational work predicts that the isolated ethanol
      CO2 complex can exist either in an electron-donor configuration or through a
      hydrogen-bonding one; yet, neither has been previously experimentally observed.
      Here, we demonstrate by rotational spectroscopy that the isolated, gas-phase
      ethanol-CO2 dimer is an electron donor-acceptor complex.

PMID- 28759237
TI  - Spectroscopic Evidence of Reversible Disassembly of the [FeFe] Hydrogenase Active
      Site.
AB  - [FeFe] hydrogenases are extremely active and efficient H2-converting
      biocatalysts. Their active site comprises a unique [2Fe] subcluster bonded to a
      canonical [4Fe-4S] cluster. The [2Fe] subsite can be introduced into hydrogenases
      lacking an assembled H-cluster through incubation with a synthesized [2Fe]H
      precursor, which initially produces the CO-inhibited state of the enzyme. We
      present FTIR spectroelectrochemical studies on the CO-inhibited state of the
      [FeFe] hydrogenase from Desulfovibrio desulfuricans, DdHydAB. At very negative
      potentials, disassembly of the H-cluster and dissociation of the [2Fe] subcluster
      is observed. Subsequently raising the potential allows cofactor rebinding and H
      cluster reassembly. This demonstrates how the stability of the [2Fe]-[4Fe-4S]
      intercluster bond depends on the applied potential and the presence of an
      inhibiting CO ligand on the [2Fe] subcluster. These results provide insight into
      the mechanisms of CO inhibition and H-cluster assembly in [FeFe] hydrogenases. A
      fundamental understanding of these properties will provide clues for designing
      better H2-converting catalysts.

PMID- 28759238
TI  - Ternary Nanoparticles with a Sheddable Shell Efficiently Deliver MicroRNA-34a
      against CD44-Positive Melanoma.
AB  - PEGylation can stabilize drug delivery systems for cancer therapy by creating
      repulsive interactions with biological components in vivo. While these
      interactions reduce nonspecific adsorption of drug-loaded particles onto
      nontarget surfaces, they also inhibit internalization of particles into target
      cells. To circumvent this so-called "PEG-dilemma", we have developed
      nanoparticles with a PEG coating that is shed after arrival in target tissue.
      Positively charged polycation nanoparticles were assembled with microRNA-34a via
      electrostatic interactions and then coated again via electrostatic interactions
      with an anionic PEG derivative that separates from the nanoparticle in the acidic
      tumor microenvironment. The resulting ternary nanoparticles with a sheddable
      shell have nearly neutral surface charge, which markedly reduces nonspecific
      adsorption. Shedding the PEG coat enhanced nanoparticle uptake into CD44-positive
      melanoma cells and promoted microRNA-34a release, which down-regulated CD44
      expression and thereby inhibited tumor growth. We conclude that nanocarriers with
      a sheddable shell show promise for cancer therapy.

PMID- 28759239
TI  - S2 Fluorescence from [26]Hexaphyrin Dianion.
AB  - S2 fluorescence from meso-hexakis(pentafluorophenyl)-substituted [26]hexaphyrin
      dianion was observed as the first example of expanded porphyrins despite its
      large molecular size and small HOMO-LUMO gap. The population kinetics among S2,
      S1, and S0 states have been studied by using femtosecond time-resolved absorption
      and fluorescence spectroscopies. Broad-band fluorescence upconversion
      spectroscopy allowed for simultaneous observation of S2 fluorescence decay in the
      visible region and S1 fluorescence rise in the NIR region, both with a time
      constant of 0.22 ps. The transient absorption spectroscopy revealed the presence
      of a direct decay path from the S2 state to the S0 state. The observation of S2
      fluorescence from highly conjugated molecular systems is quite rare, and S2
      fluorescence beyond 700 nm is also quite rare.

PMID- 28759240
TI  - Strong Stretching of Poly(ethylene glycol) Brushes Mediated by Ionic Liquid
      Solvation.
AB  - We have measured forces between mica surfaces coated with a poly(ethylene glycol)
      (PEG) brush solvated by a vacuum-dry ionic liquid, 1-ethyl-3-methyl imidazolium
      bis(trifluoromethylsulfonyl)imide, with a surface forces apparatus. At high
      grafting density, the solvation mediated by the ionic liquid causes the brush to
      stretch twice as much as in water. Modeling of the steric repulsion indicates
      that PEG behaves as a polyelectrolyte; the hydrogen bonding between ethylene
      glycol and the imidazolium cation seems to effectively charge the polymer brush,
      which justifies the strong stretching. Importantly, under strong polymer
      compression, solvation layers are squeezed out at a higher rate than for the neat
      ionic liquid. We propose that the thermal fluctuations of the PEG chains, larger
      in the brush than in the mushroom configuration, maintain the fluidity of the
      ionic liquid under strong compression, in contrast to the solid-like squeezing
      out behavior of the neat ionic liquid. This is the first experimental study of
      the behavior of a polymer brush solvated by an ionic liquid under
      nanoconfinement.

PMID- 28759241
TI  - Surfactant-Induced Patterns in Polymer Brushes.
AB  - The properties of surfaces with grafted macromolecules are determined by a fine
      structure of the macromolecular layer, whereas the mixtures of macromolecules
      with surfactants are very rich in structure types. Using the scaling mean-field
      theory, we consider the self-assembly in polymer brushes into various patterns
      induced by interactions with low-molecular surfactants. The interaction energies
      of the parts of a surfactant molecule with the polymer units are assumed to be
      greatly different. With increasing the grafting density, the formation of
      lamellae perpendicular to the grafting plane, a continuous layer with oblong or
      round pores, or a homogeneous brush is predicted. The driving force of the
      pattern formation is a gain in the interaction energy of surfactant molecules
      oriented at the lateral surfaces of lamellae or pores. The process of pore
      formation in a homogeneous brush caused by a temperature change at definite
      grafting densities is described as the first-order phase transition. It is
      accompanied by a stepwise extension of the brush and by orientational ordering of
      surfactant molecules. The transitions between the other patterns are of the
      second order. The thickness of lamellae and the distance between pores are
      approximately twice the surfactant molecule size except for the extremely high
      grafting densities. The diagrams of brush patterns are presented and discussed.

PMID- 28759242
TI  - Photochemical Rearrangement of Diarylethenes: Reaction Efficiency and Substituent
      Effects.
AB  - In recent years, great synthetic potential of the photorearrangement of
      diarylethenes leading to naphthalene derivatives via a cascade process of
      photocyclization/[1,n]-H shift/cycloreversion has been demonstrated. In this
      work, first a multifaceted study of the influence of various factors on the
      efficiency of the photorearrangement of diarylethenes of furanone series
      containing benzene and oxazole derivatives as aryl residues has been carried out.
      The efficiency of this phototransformation (quantum yields) and the effect of
      methoxy substituents in the phenyl moiety have been studied. Despite the
      multistage process, the quantum yields of the photorearrangement are rather high
      (0.34-0.49). It has been found that the efficiency of photocyclization of
      diarylethenes increases with the introduction of electron-donating methoxy groups
      in the phenyl moiety. Using the DFT calculations, we have been able to estimate
      in the photoinduced isomer the distance between hydrogen atom and carbon atom to
      which it migrates in the result of the sigmatropic shift. For all studied
      diarylethenes, this value was 2.67-2.73 A, which is less than the sum of van der
      Waals radii of carbon and hydrogen atoms (2.9 A).

PMID- 28759243
TI  - Telecom-Wavelength Bottom-up Nanobeam Lasers on Silicon-on-Insulator.
AB  - Semiconductor nanowire lasers are considered promising ultracompact and energy
      efficient light sources in the field of nanophotonics. Although the integration
      of nanowire lasers onto silicon photonic platforms is an innovative path toward
      chip-scale optical communications and photonic integrated circuits, operating
      nanowire lasers at telecom-wavelengths remains challenging. Here, we report on
      InGaAs nanowire array lasers on a silicon-on-insulator platform operating up to
      1440 nm at room temperature. Bottom-up photonic crystal nanobeam cavities are
      formed by growing nanowires as ordered arrays using selective-area epitaxy, and
      single-mode lasing by optical pumping is demonstrated. We also show that arrays
      of nanobeam lasers with individually tunable wavelengths can be integrated on a
      single chip by the simple adjustment of the lithographically defined growth
      pattern. These results exemplify a practical approach toward nanowire lasers for
      silicon photonics.

PMID- 28759244
TI  - Controlling the Heat Dissipation in Temperature-Matched Plasmonic Nanostructures.
AB  - Heat dissipation in a plasmonic nanostructure is generally assumed to be ruled
      only by its own optical response even though also the temperature should be
      considered for determining the actual energy-to-heat conversion. Indeed,
      temperature influences the optical response of the nanostructure by affecting its
      absorption efficiency. Here, we show both theoretically and experimentally how,
      by properly nanopatterning a metallic surface, it is possible to increase or
      decrease the light-to-heat conversion rate depending on the temperature of the
      system. In particular, by borrowing the concept of matching condition from the
      classical antenna theory, we first analytically demonstrate how the temperature
      sets a maximum value for the absorption efficiency and how this quantity can be
      tuned, thus leading to a temperature-controlled optical heat dissipation. In
      fact, we show how the nonlinear dependence of the absorption on the electron
      phonon damping can be maximized at a specific temperature, depending on the
      system geometry. In this regard, experimental results supported by numerical
      calculations are presented, showing how geometrically different nanostructures
      can lead to opposite dependence of the heat dissipation on the temperature, hence
      suggesting the fascinating possibility of employing plasmonic nanostructures to
      tailor the light-to-heat conversion rate of the system.

PMID- 28759245
TI  - Au Exchange or Au Deposition: Dual Reaction Pathways in Au-CsPbBr3
      Heterostructure Nanoparticles.
AB  - We have designed a facile synthetic strategy for the selective deposition of Au
      metal on all-inorganic CsPbBr3 perovskite nanocrystals that includes the addition
      of PbBr2 salt along with AuBr3 salt. PbBr2 is necessary because the addition of
      Au3+ to solutions of CsPbBr3 nanocrystals otherwise results in the exchange of
      Au3+ ions from solution with Pb2+ cations within the nanocrystal lattice to
      produce Cs2AuIAuIIIBr6 nanocrystals with a tetragonal crystal structure and a
      band gap of about 1.6 eV, in addition to Au metal deposition. Including excess
      Pb2+ ions in solution prevents the exchange reaction. Au metal deposits on the
      surface of the nanocrystals to produce the Au-CsPbBr3 heterostructure
      nanoparticles with an Au particle diameter determined by the Au3+ ion
      concentration. Fluorescence quenching caused by Au deposition monotonically
      increases with deposition size, but the fluorescence quantum yield (QY) is
      significantly greater than if any cation exchange has occurred. An optimized
      synthesis can produce Au-CsPbBr3 nanoparticles with 70% QY and no evidence of
      cation exchange.

PMID- 28759246
TI  - Optical Anisotropy of Topologically Distorted Semiconductor Nanocrystals.
AB  - Engineering nanostructured optical materials via the purposeful distortion of
      their constituent nanocrystals requires the knowledge of how various distortions
      affect the nanocrystals' electronic subsystem and its interaction with light. We
      use the geometric theory of defects in solids to calculate the linear
      permittivity tensor of semiconductor nanocrystals whose crystal lattice is
      arbitrarily distorted by imperfections or strains. The result is then employed to
      systematically analyze the optical properties of nanocrystals with spatial
      dispersion caused by screw dislocations and Eshelby twists. We demonstrate that
      Eshelby twists create gyrotropy in nanocrystals made of isotropic semiconductors
      whereas screw dislocations can produce it only if the nanocrystal material itself
      is inherently anisotropic. We also show that the dependence of circular dichroism
      spectrum on the aspect ratio of dislocation-distorted semiconductor nanorods
      allows resonant enhancing their optical activity (at least by a factor of 2) and
      creating highly optically active nanomaterials.

PMID- 28759247
TI  - A Rare Water and Hydroxyl-Extended One-Dimensional Dysprosium(III) Chain and Its
      Magnetic Dilution Effect.
AB  - A novel water and hydroxyl-extended one-dimensional dysprosium(III) chain was
      hydrothermally obtained, which exhibits a relatively high spin-reversal energy
      barrier of 88.7 K and intrachain ferromagnetic interaction with the coupling
      constant Jexch = 3.04 cm-1 calculated by fitting magnetic susceptibilities using
      POLY_ANISO program based on ab initio calculations. To deeply understand the
      respective role of the single-ion anisotropy and intrachain exchange on the
      effective energy barrier, three crystallographically isostructural analogues
      containing isotropic Gd(III)-, diamagnetic Y(III)-, as well as Y(III)-doped
      Dy0.05Y0.95 were prepared and characterized structurally and magnetically. Due to
      the absence of significant intrachain exchange interaction, the effective energy
      barrier of the Dy0.05Y0.95 decreased by 9.9 K as compared with that of parent
      dysprosium(III) chain. Thus, it can be concluded that the intrachain
      ferromagnetic coupling and the magnetic anisotropy of the Dy(III) ion
      synergistically enhance the effective energy barrier of the dysprosium(III)
      chain, in which the single-ion anisotropy becomes more predominant.

PMID- 28759248
TI  - Chemo- and Diastereoselective Michael-Michael-Acetalization Cascade for the
      Synthesis of 1,3-Indandione-Fused Spiro[4.5]decan Scaffolds.
AB  - A novel, organobase-catalyzed and highly chemoselective Michael-Michael
      acetalization cascade is presented for the efficient synthesis of spiro
      indandione skeletons. Following this very simple protocol, a broad range of
      products was obtained in good yields with excellent diastereocontrol. The role of
      steric factors in the acetalization step was evaluated.

PMID- 28759249
TI  - Understanding the Enhanced Magnetic Response of Aminocholesterol Doped Lanthanide
      Ion-Chelating Phospholipid Bicelles.
AB  - Cholesterol (Chol-OH) and its conjugates are powerful molecules for engineering
      the physicochemical and magnetic properties of phospholipid bilayers in bicelles.
      Introduction of aminocholesterol (3beta-amino-5-cholestene, Chol-NH2) in bicelles
      composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and the thulium
      ion-chelating phospholipid 1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine
      diethylene triaminepentaacetate (DMPE-DTPA/Tm3+) results in unprecedented high
      magnetic alignments by selectively tuning the magnetic susceptibility Deltachi of
      the bilayer. However, little is known on the underlying mechanisms behind the
      magnetic response and, more generally, on the physicochemical forces governing a
      Chol-NH2 doped DMPC bilayer. We tackled this shortcoming with a multiscale bottom
      up comparative investigation of Chol-OH and Chol-NH2 mixed with DMPC. First,
      simplified monolayer models on a Langmuir trough were employed to compare the two
      steroid molecules at various contents in DMPC. In a second step, a molecular
      dynamics (MD) simulation allowed for a more representative model of the bicelle
      bilayer while monitoring the amphiphiles and their interactions on the molecular
      level. In a final step, we moved away from the models and investigated the effect
      of temperature on the structure and magnetic alignment of Chol-NH2 doped bicelles
      by SANS. The DMPC/steroid monolayer studies showed that Chol-OH induces a larger
      condensation effect than Chol-NH2 at steroid contents of 16 and 20 mol %.
      However, this tendency was inversed at steroid contents of 10, 30, and 40 mol %.
      Although the MD simulation with 16 mol % steroid revealed that both compounds
      induce a liquid-ordered state in DMPC, the bilayer containing Chol-NH2 was much
      less ordered than the analogous system containing Chol-OH. Chol-NH2 underwent
      significantly more hydrogen bonding interactions with neighboring DMPC lipids
      than Chol-OH. It seems that, by altering the dynamics of the hydrophilic
      environment of the bicelle, Chol-NH2 changes the crystal field and angle of the
      phospholipid-lanthanide DMPE-DTPA/Tm3+ complex. These parameters largely
      determine the magnetic susceptibility Deltachi of the complex, explaining the
      SANS results, which show significant differences in magnetic alignment of the
      steroid doped bicelles. Highly magnetically alignable DMPC/Chol-NH2/DMPE
      DTPA/Tm3+ (molar ratio 16:4:5:5) bicelles were achieved up to temperatures of 35 
      degrees C before a thermoreversible rearrangement into nonalignable vesicles
      occurred. The results confirm the potential of Chol-NH2 doped bicelles to act as
      building blocks for the development of the magnetically responsive soft materials
      of tomorrow.

PMID- 28759250
TI  - Direct Observation of the Band Gap Transition in Atomically Thin ReS2.
AB  - ReS2 is considered as a promising candidate for novel electronic and sensor
      applications. The low crystal symmetry of this van der Waals compound leads to a
      highly anisotropic optical, vibrational, and transport behavior. However, the
      details of the electronic band structure of this fascinating material are still
      largely unexplored. We present a momentum-resolved study of the electronic
      structure of monolayer, bilayer, and bulk ReS2 using k-space photoemission
      microscopy in combination with first-principles calculations. We demonstrate that
      the valence electrons in bulk ReS2 are-contrary to assumptions in recent
      literature-significantly delocalized across the van der Waals gap. Furthermore,
      we directly observe the evolution of the valence band dispersion as a function of
      the number of layers, revealing the transition from an indirect band gap in bulk
      ReS2 to a direct gap in the bilayer and the monolayer. We also find a
      significantly increased effective hole mass in single-layer crystals. Our results
      establish bilayer ReS2 as an advantageous building block for two-dimensional
      devices and van der Waals heterostructures.

PMID- 28759251
TI  - Toxoplasma gondii, a Foodborne Pathogen in the Swine Production Chain from a
      European Perspective.
AB  - Toxoplasmosis is a foodborne zoonosis transmitted by Toxoplasma gondii, a
      cosmopolitan protozoan that infects humans through exposure to different parasite
      stages, in particular by ingestion of tissue cysts or tachyzoites contained in
      meat, primary offal (viscera), and meat-derived products or ingestion of
      environmental sporulated oocysts in contaminated food or water. The pig is an
      important species for infection: raw or undercooked pork consumption not subject
      to treatment able to inactivate the parasite represents a risk to consumers'
      health. Broadening knowledge of transmission ways and prevalence concerning this
      important pathogen in swine, together with a thorough acquaintance with hazard
      management are key elements to avoid T. gondii spreading within the swine
      production chain. This review aims to illustrate why toxoplasmosis should be
      regarded as a veterinary public health issue through a careful description of the
      parasite, routes of infection, and inactivation treatments, highlighting the main
      prevention lines from pig breeding to pork consumption.

PMID- 28759252
TI  - Long Noncoding RNA Cancer Susceptibility Candidate 8 Suppresses the Proliferation
      of Bladder Cancer Cells via Regulating Glycolysis.
AB  - Increasing evidence highlights the critical regulatory role of long noncoding
      RNAs (lncRNAs) in carcinogenesis. Bladder cancer has become the most prevalent
      urologic malignancy, which is commonly diagnosed among adults. In this study, we
      showed that the lncRNA cancer susceptibility candidate 8 (CASC8) is significantly
      downregulated in bladder cancers and associated with the advanced stage of
      bladder cancer patients. Overexpression of CASC8 remarkably suppressed the
      bladder cancer cell proliferation. Mechanistically, we illustrated that CASC8
      reduced the glycolysis of bladder cancer cells via interacting with the
      fibroblast growth factor receptor 1 (FGFR1). The binding of CASC8 with FGFR1
      inhibits FGFR1-mediated lactate dehydrogenase A phosphorylation, which attenuates
      the conversion of pyruvate into lactate. Collectively, our findings uncovered the
      pivotal role of CASC8 in bladder tumorigenesis and suggested that CASC8 may
      function as a candidate biomarker for the diagnosis of bladder cancer.

PMID- 28759254
TI  - Emerging Utility of Virtual Reality as a Multidisciplinary Tool in Clinical
      Medicine.
AB  - OBJECTIVE: Among the more recent products borne of the evolution of digital
      technology, virtual reality (VR) is gaining a foothold in clinical medicine as an
      adjunct to traditional therapies. Early studies suggest a growing role for VR
      applications in pain management, clinical skills training, cognitive assessment
      and cognitive therapy, and physical rehabilitation. MATERIALS AND METHODS: To
      complete a review of the literature, we searched PubMed and MEDLINE databases
      with the following search terms: "virtual reality," "procedural medicine,"
      "oncology," "physical therapy," and "burn." We further limited our search to
      publications in the English language. Boolean operators were used to combine
      search terms. RESULTS: The included search terms yielded 97 potential articles,
      of which 45 were identified as meeting study criteria, and are included in this
      review. These articles provide data, which strongly support the hypothesis that
      VR simulations can enhance pain management (by reducing patient perception of
      pain and anxiety), can augment clinical training curricula and physical
      rehabilitation protocols (through immersive audiovisual environments), and can
      improve clinical assessment of cognitive function (through improved ecological
      validity). CONCLUSION: Through computer-generated, life-like digital landscapes,
      VR stands to change the current approach to pain management, medical training,
      neurocognitive diagnosis, and physical rehabilitation. Additional studies are
      needed to help define best practices in VR utilization, and to explore new
      therapeutic uses for VR in clinical practice.

PMID- 28759253
TI  - Differential Recognition of Mycobacterium tuberculosis-Specific Epitopes as a
      Function of Tuberculosis Disease History.
AB  - RATIONALE: Individuals with a history of tuberculosis (TB) disease are at
      elevated risk of disease recurrence. The underlying cause is not known, but one
      explanation is that previous disease results in less-effective immunity against
      Mycobacterium tuberculosis (Mtb). OBJECTIVES: We hypothesized that the repertoire
      of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb
      infection differs as a function of previous diagnosis of active TB disease.
      METHODS: T-cell responses to peptide pools in samples collected from an adult
      screening and an adolescent validation cohort were measured by IFN-gamma enzyme
      linked immunospot assay or intracellular cytokine staining. MEASUREMENTS AND MAIN
      RESULTS: We identified a set of "type 2" T-cell epitopes that were recognized at
      10-fold-lower levels in Mtb-infected individuals with a history of TB disease
      less than 6 years ago than in those without previous TB. By contrast, "type 1"
      epitopes were recognized equally well in individuals with or without previous TB.
      The differential epitope recognition was not due to differences in HLA class II
      binding, memory phenotypes, or gene expression in the responding T cells.
      Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P <
      0.0001) more homologous to sequences from bacteria found in the human microbiome
      than type 1 epitopes. CONCLUSIONS: Preferential loss of T-cell reactivity to Mtb
      epitopes that are homologous to bacteria in the microbiome in persons with
      previous TB disease may reflect long-term effects of antibiotic TB treatment on
      the microbiome.

PMID- 28759255
TI  - Child Development and the Community Environment: Understanding Overweight across
      the Income Gradient.
AB  - BACKGROUND: Childhood obesity is associated with increased risk of long-term
      health consequences. Despite the wealth of research, prevalence rates are still
      high, particularly among lower-income groups. Little is known about variations in
      risk of overweight/obesity across income gradients and the adolescent
      developmental stage. This study examines the association between distal community
      factors and adolescent weight status across income gradients and whether this
      association is moderated by age. METHODS: Using a nationally representative
      sample of 33,096 adolescents drawn from the National Survey of Children's Health
      (NSCH), this study assesses how age interacts with community factors and weight
      (overweight/obese vs. normal weight) after controlling for individual-level
      factors (gender, race/ethnicity, household composition, parental employment,
      education) in subsamples stratified by income quartile (according to federal
      poverty guidelines). Community factors include community risk (comprising
      community safety, school safety, neighborhood cohesion, and detracting
      neighborhood elements) and four neighborhood amenities (sidewalks, parks,
      recreation centers, libraries). RESULTS: Adolescents with low community risk in
      quartiles 1 and 3 had lower odds of overweight/obesity (by 32% and 35%,
      respectively) compared with the high community risk group. Age interacted with
      access to recreational centers in quartile 1 and sidewalks in quartile 4,
      indicating a decrease in odds of overweight/obesity (by 17% and 9%, respectively)
      with access to these amenities as youth age. CONCLUSIONS: Findings suggest that
      predictors of overweight/obesity can be diverse within income groups, and future
      research and interventions should address distinct features of each community.
      This includes reducing detracting elements and enhancing amenities and cohesion
      in lower quartiles, as well as improving walkability in the highest quartile.

PMID- 28759257
TI  - In Search of Lost Small Peptides.
AB  - A large body of evidence indicates that genome annotation pipelines have biased
      our view of coding sequences because they generally undersample small proteins
      and peptides. The recent development of genome-wide translation profiling reveals
      the prevalence of small/short open reading frames (smORFs or sORFs), which are
      scattered over all classes of transcripts, including both mRNAs and presumptive
      long noncoding RNAs. Proteomic approaches further confirm an unexpected variety
      of smORF-encoded peptides (SEPs), representing an overlooked reservoir of
      bioactive molecules. Indeed, functional studies in a broad range of species from
      yeast to humans demonstrate that SEPs can harbor key activities for the control
      of development, differentiation, and physiology. Here we summarize recent
      advances in the discovery and functional characterization of smORF/SEPs and
      discuss why these small players can no longer be ignored with regard to genome
      function.

PMID- 28759256
TI  - Rethinking m6A Readers, Writers, and Erasers.
AB  - In recent years, m6A has emerged as an abundant and dynamically regulated
      modification throughout the transcriptome. Recent technological advances have
      enabled the transcriptome-wide identification of m6A residues, which in turn has
      provided important insights into the biology and regulation of this pervasive
      regulatory mark. Also central to our current understanding of m6A are the
      discovery and characterization of m6A readers, writers, and erasers. Over the
      last few years, studies into the function of these proteins have led to important
      discoveries about the regulation and function of m6A. However, during this time
      our understanding of these proteins has also evolved considerably, sometimes
      leading to the reversal of early concepts regarding the reading, writing and
      erasing of m6A. In this review, we summarize recent advances in m6A research, and
      we highlight how these new findings have reshaped our understanding of how m6A is
      regulated in the transcriptome.

PMID- 28759259
TI  - End of the Road for Adjunctive Vitamin D Therapy for Pulmonary Tuberculosis?

PMID- 28759258
TI  - Nonantimicrobial drug targets for Clostridium difficile infections.
AB  - Clostridium difficile infection (CDI) is a major public health problem worldwide.
      Treatment has become complicated due to the emergence of strains with increased
      toxigenicity and sporulation rate, together with rampant antibiotics use that
      disrupts colonization resistance of the colonic microbiota. As a result, there is
      a critical need for nonantibiotic treatments. Therapies based on inhibiting the
      toxins, bacterial structures responsible for colonization, virulence and
      restoration of the gut microbiota are the most important nonantibiotic targets to
      combat CDI. This report outlines these targets and how they could become the
      focus of future therapeutic agents. Inhibiting colonization and virulence factors
      during CDI will disrupt pathogen persistence and decrease exposure to the
      inflammatory toxins, allowing the immune system to clear the infection.

PMID- 28759261
TI  - Tongue-Tied About Tongue-Ties and Breast Milk Composition.

PMID- 28759262
TI  - A Double-Blind and Placebo-Controlled Trial of Aripiprazole in Symptomatic Youths
      at Genetic High Risk for Bipolar Disorder.
AB  - OBJECTIVE: To determine if acute treatment with aripiprazole (APZ) would be
      superior to treatment with placebo in reducing dysfunctional symptoms of elevated
      mood and/or irritability in symptomatic children and adolescents at familial high
      risk for bipolar disorder (BPD) whose mood episodes occur spontaneously. These
      are patients we have previously referred to as suffering from "cyclotaxia."
      METHODS: This was single-site, randomized, double-blind, placebo-controlled
      outpatient clinical trial in which youths aged 5-17 years who met diagnostic
      criteria for either cyclothymic disorder (CYC) or BPD not otherwise specified (BP
      NOS) were randomly assigned to receive either APZ or placebo. Eligible
      participants had at least one parent with BPD, another first- or second-degree
      relative afflicted with a mood disorder, and also had not responded to
      psychotherapy. Treatment with APZ was initiated at a dose of approximately 0.1
      mg/kg/day and could be increased by approximately 0.05 mg/kg/day at each study
      visit. Patients were seen weekly for 4 weeks and then every other week thereafter
      for 12 weeks. The primary outcome measure was mean change from baseline on Young
      Mania Rating Scale (YMRS) total score. RESULTS: A total of 59 patients (30 APZ,
      29 placebo) aged 11.8 (SD = 2.7) years were randomized and returned for at least
      one postbaseline assessment. The mean total daily doses of active APZ and placebo
      were 7.1 mg (SD = 3.7) and 7.4 mg (SD = 4.2), respectively. At the 12-week time
      point, APZ was superior to placebo on the primary outcome measure (p < 0.005).
      Most adverse events were mild and transient in nature. There was a significant
      difference in weight gain from baseline between patients who received APZ (2.3 kg
      [SD = 3.3]) and those who received placebo (0.7 kg [SD = 1.8]). CONCLUSION: This
      double-blind trial found that APZ was significantly more efficacious than placebo
      in reducing symptoms of mania in children and adolescents with cyclotaxia.

PMID- 28759260
TI  - Nocturnal Oximetry-based Evaluation of Habitually Snoring Children.
AB  - RATIONALE: The vast majority of children around the world undergoing
      adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not
      objectively diagnosed by nocturnal polysomnography because of access availability
      and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is
      readily and globally available, could potentially provide a reliable and
      convenient diagnostic approach for pediatric OSA. METHODS: Deidentified nSpO2
      recordings from a total of 4,191 children originating from 13 pediatric sleep
      laboratories around the world were prospectively evaluated after developing and
      validating an automated neural network algorithm using an initial set of single
      channel nSpO2 recordings from 589 patients referred for suspected OSA.
      MEASUREMENTS AND MAIN RESULTS: The automatically estimated apnea-hypopnea index
      (AHI) showed high agreement with AHI from conventional polysomnography
      (intraclass correlation coefficient, 0.785) when tested in 3,602 additional
      subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10
      events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2%
      accuracy; 0.788, 0.854, and 0.913 area under the receiver operating
      characteristic curve, respectively). CONCLUSIONS: Neural network-based automated
      analyses of nSpO2 recordings provide accurate identification of OSA severity
      among habitually snoring children with a high pretest probability of OSA. Thus,
      nocturnal oximetry may enable a simple and effective diagnostic alternative to
      nocturnal polysomnography, leading to more timely interventions and potentially
      improved outcomes.

PMID- 28759263
TI  - Developing Clinical Guidelines: 99% Faster Is Not Enough.

PMID- 28759264
TI  - Breastfeeding Education and Support Services Provided to Family Medicine and
      Obstetrics-Gynecology Residents.
AB  - BACKGROUND: Breastfeeding education is known to be insufficient in pediatric
      (PEDS) training and is, in part, responsible for suboptimal rates of
      breastfeeding. No recent studies about the level of education provided to family
      medicine (FM) and obstetrics-gynecology (OB) residency trainees are available.
      OBJECTIVES: This study was conducted to investigate breastfeeding education and
      support services provided to FM and OB residents in the United States. The
      results were compared with a 2011 study of PEDS residents. METHODS: A cross
      sectional study was conducted using a web-based survey emailed to program
      directors (PDs) of FM and OB residency programs in the United States. RESULTS:
      Eighteen percent of PDs (95 of 515) completed the survey. Of these, 88% answered
      questions regarding education and support services provided. A median of 23 hours
      of breastfeeding education is provided to OB residents (4-year program) and 8
      hours provided to FM residents (3-year program). In comparison, PEDS programs
      reported a median of 9 hours. The most commonly used settings included lectures
      with faculty and lactation consultants, similar to the PEDS study. Approximately
      75% of respondents cited barriers to educating residents, with limited resident
      time being the most common. Eighty-one percent of respondents identified
      breastfeeding rooms as the service most frequently provided to residents who
      breastfeed. CONCLUSIONS: FM and PEDS residents are provided similar amounts of
      breastfeeding education, while OB programs provide more education, but in
      different settings. Reported barriers to this education are similar in all
      specialties. Support services are more commonly provided in PEDS programs.

PMID- 28759265
TI  - From Lemongrass to Ivermectin: Ethnomedical Management of Chagas Disease in
      Tropical Bolivia.
AB  - Chagas disease is a neglected tropical disease; the only viable drugs are
      outdated and produce frequent side effects, and the overwhelming majority of
      cases are undiagnosed and untreated. Globally, people encounter numerous
      impediments to accessing biomedical treatment for Chagas disease. However, little
      is known about how people with Chagas disease manage their health outside the
      biomedical system. In this article, I discuss knowledge of ethnomedical
      treatments among marginalized patients in an endemic area of Bolivia. I
      interviewed 68 patients, 63 (93 percent) of whom had positive diagnoses for
      Chagas disease. Participants free listed 66 ethnomedical remedies either for
      Chagas disease (n = 39) or its cardiac symptoms. Participants stressed the
      accessibility of ethnomedical remedies in contrast to the multiple barriers to
      accessing biomedical treatment. Far from eroding in the face of globalization and
      sociopolitical marginalization, ethnomedical knowledge in the study area is
      dynamic and flexible, communicated through various channels.

PMID- 28759266
TI  - Evaluation of the PAI-A Anxiety and Depression Scales: Evidence of Construct
      Validity.
AB  - Against the background of a dearth of studies examining the properties of the
      scale scores of the Personality Assessment Inventory-Adolescent (PAI-A; Morey,
      2007), this study was conducted to evaluate evidence of construct validity for
      the Anxiety (ANX) and Depression (DEP) scales of the PAI-A. Convergent and
      discriminant validity of the ANX and DEP scale scores were investigated using a
      sample of adolescents admitted to the adolescent program of a private tertiary
      care inpatient treatment facility. Multiple methods assessing anxious and
      depressive symptomology and diagnoses were included. Construct validity of the
      ANX and DEP scales was mostly supported. Advantages of using the PAI-A for the
      assessment of anxiety and depression were discussed.

PMID- 28759267
TI  - The Infernal Alternatives of Corporate Pharmaceutical Research: Abandoning
      Psychiatry.
AB  - What happens when health research is measured by market size? How does this
      change the dynamics of medical research, and how is its growth envisioned and
      managed? In this article, I build on my arguments in Drugs for Life: How
      Pharmaceutical Companies Define our Health, which focused primarily on the
      development and marketing of mass medications for heart disease and I examine the
      market dynamics that are used to drive research into and out of psychiatric and
      other neuromedicines, such as the closing of mental health research at most major
      pharmaceutical companies. Industry compares entire sectors of medical research to
      evaluate their relative chances of profits and growth; it is willing to sacrifice
      a whole region of effective and profitable medicine if it can grow profits more
      in other regions. Baudrillard, Pignarre, and Stengers are used to consider
      whether this situation can best be described as one of infernal alternatives, and
      how to analyze the responses of psychiatric leaders.

PMID- 28759269
TI  - Disrupted circadian rhythms of body temperature, heart rate and fasting blood
      glucose in prediabetes and type 2 diabetes mellitus.
AB  - We report a progressive disruption of 24-h rhythms in fasting blood glucose
      (FBG), body temperature (BT) and heart rate (HR) associated with metabolic
      dysfunction and the development of prediabetes (PD) and type 2 diabetes mellitus
      (T2DM) in overweight middle-aged (40-69 years old) humans. Increasing BT and HR
      mean values and declining 24-h BT and HR amplitudes accompany adverse changes in
      metabolic state. Increased nocturnal BT and a phase delay of the 24-h BT rhythm,
      deviant 24-h HR profile and a phase advance of the 24-h HR and FBG rhythms are
      early signs of the PD metabolic state. In T2DM, the 24-h FBG rhythm is no longer
      detectable, and the 24-h amplitudes of BT and HR are greatly diminished. In
      addition, lepton and creatinine values were lowered in T2DM. Moreover, positive
      correlations between FBG and body mass index, BMI, and negative correlations
      between the 24-h amplitude of FBG and BMI indicate that overweight is an
      additional factor causing disruption of the circadian rhythms. Further studies on
      circadian disruption as a consequence of metabolic dysfunction are necessary. The
      quantitative analysis of changing circadian BT and HR rhythms may provide
      prognostic markers of T2DM and therapeutic targets for its prevention and
      correction.

PMID- 28759268
TI  - Relationship between neuropsychological tests and driver's license renewal tests
      in Parkinson's disease.
AB  - OBJECTIVE: To determine whether the standard Spanish driving test (ASDE test) was
      able to identify patients with Parkinson's disease (PD) at risk of unsafe driving
      and to examine the relationship between the ASDE test and the Useful Field of
      View (UFOV) as well as with a battery of neuropsychological tests in drivers with
      PD. METHODS: Thirty-seven patients with PD and 33 controls matched by age and
      education level were included in an observational study. All participants were
      active drivers and patients with PD underwent study procedures after taking the
      medication in the "on" period. Subjects with a Mini-Mental State Examination
      (MMSE) score <= 24 were excluded. Neuropsychological tests (Repeatable Battery
      for Neuropsychological Status [RBANS], Trail Making Test [TMT-A and -B], and
      Block Design test), driving performance tests (ASDE Driver Test and UFOV), and
      daytime sleepiness (Epworth Sleepiness Scale) were assessed. RESULTS: The PD
      group performed significantly worse than healthy controls in the ASDE Motor
      Coordination tests. No significant differences were observed in anticipation
      speed, multiple reaction time, concentrated attention, and resistance to
      monotony. All participants successfully completed the UFOV tests. Statistically
      significant differences between patients with PD and controls were found in
      processing speed (UFOV1; P =.03) and more patients with PD were found in the
      categories of higher driving risk levels (P =.03). In addition, patients with PD
      showed worse scores than healthy controls in visuospatial capacities (Line
      Orientation), psychomotor speed (Coding and TMT-A), memory (List Recognition,
      Story Recall), and executive function (TMT-B). The driving tests (ASDE and UFOV)
      showed a low sensitivity and a high specificity but a higher percentage of
      patients in the PD group failed in multiple reaction time, concentrated
      attention, and resistance to monotony. In addition, 18.9% of patients with PD
      showed a cutoff of 4 for UFOV risk. In the discriminant analysis, Line
      Orientation (visuospatial/constructive domain) and Figure Recall (delayed memory)
      were found to be statistically significant with a rate of correct classification
      of unsafe drivers with PD of 78.2%. In addition, normal results on the Line
      Orientation item were associated with a 1.5 times higher probability of non-risky
      driving in the multivariate analysis. CONCLUSIONS: At early stages of the
      disease, about 19% of patients with PD showed difficulties that may affect their
      driving capabilities. Line Orientation and Figure Recall are useful to alert
      clinicians to the risk of unsafe driving. For this reason, patients with PD
      should be evaluated for driving abilities more regularly to determine the extent
      of deficits that may influence driving performance.

PMID- 28759270
TI  - Associations between chronotypes and psychological vulnerability factors of
      depression.
AB  - Chronotypes have been associated with psychopathology. The eveningness chronotype
      has been consistently linked with depressed states or depressive disorder, but
      the underlying mechanism remains unclear. Prior studies have shown associations
      between chronotype and personality traits that are linked to depression (e.g.
      neuroticism), but other psychological vulnerability factors have not been
      previously investigated in relation to chronotypes. The aim of this study was to
      examine the association between chronotypes, depression and psychological risk
      factors of depression (namely, cognitive reactivity and worry), in a large cohort
      of depressed patients and healthy individuals. We used data from the Netherlands
      Study of Depression and Anxiety (n = 1654), which includes 1227 clinically
      diagnosed individuals with a lifetime diagnosis of depression and 427 healthy
      controls. We assessed cognitive reactivity (Leiden Index of Depression
      Sensitivity-Revised) and trait worry (Penn State Worry Questionnaire). We
      controlled for sociodemographic factors as well as for insomnia and neuroticism.
      We found that the evening type is associated with higher cognitive reactivity
      scores, especially with increased rumination. Cognitive reactivity also mediated
      the relationship between chronotype and depression status, even when controlling
      for neuroticism and insomnia. Trait worry was not associated with chronotype. Our
      findings show that depressogenic cognitions are more prevalent in evening types
      and perhaps mediate the association between chronotype and depression. Further
      prospective research is needed to determine the timeline of the association.
      Nevertheless, results imply that targeting depressogenic cognitive processes,
      perhaps in combination with chronotherapeutic treatments, may be particularly
      useful in evening types.

PMID- 28759271
TI  - Medication use, sleep, and caregiver smoking status among urban children with
      asthma.
AB  - OBJECTIVE: Children living in urban settings from low-income, minority families
      are at a high risk for experiencing asthma morbidity. Environmental tobacco smoke
      (ETS, i.e., secondhand) exposure, typically from caregiver smoking, has been
      associated with increased quick-relief medication use and child nocturnal
      awakenings due to increased asthma symptoms as well as worse sleep quality in
      children with asthma. This study investigated the moderating role of caregiver
      smoking status on the association between quick-relief medication use and child's
      sleep quality in urban children with persistent asthma. METHODS: Fifty-four urban
      children with persistent asthma and their primary caregivers completed a baseline
      research session. Caregivers then completed ecological momentary assessment
      surveys via smartphones twice daily for two weeks in which smoking behaviors,
      child quick-relief medication use, and child's sleep quality were assessed.
      RESULTS: Twenty caregivers (37%) reported smoking at least one day across the two
      week period. The caregiver smoking status significantly moderated the association
      between quick-relief medication use and child's sleep quality after controlling
      for child age and monthly household income. The caregiver smoking status
      exacerbated the association between quick-relief medication use and child's sleep
      quality, such that more medication usage was associated with worse sleep quality.
      CONCLUSIONS: Findings suggest that in urban families with a caregiver who smokes,
      more daily quick-relief medication use may put children at an increased risk for
      worse sleep quality. The effects of ETS exposure on child's sleep quality in
      addition to child asthma symptoms should be an integral part of discussions
      between pediatric healthcare providers and families of children with asthma.

PMID- 28759272
TI  - Determination of asthma control using administrative data regarding short-acting
      beta-agonist inhaler purchase.
AB  - BACKGROUND: Symptom control is a primary goal in asthma. We hypothesized that
      administrative data regarding rescue inhaler purchases may correlate with asthma
      symptom control. METHODS: We identified all patients who purchased short-acting
      beta-agonist (SABA) inhalers during the course of one year in the database of a
      Health Maintenance Organization (HMO). Primary physicians identified asthma
      patients and classified their asthma symptom control into three groups according
      to the Global Initiative for Asthma (GINA) guidelines. Asthma patients were asked
      to answer symptom questionnaires and grade their asthma control. SABA inhaler
      purchases were compared between asthma control groups as classified by the
      guidelines, the physicians and the patients. We also compared the agreement on
      asthma control between the three methods of classification. RESULTS: Of 241
      asthma patients, 83 completed the questionnaires. Using the GINA guidelines
      criteria, 26 were symptom controlled, 46 were partially controlled and 11 were
      uncontrolled. SABA inhaler purchases were not significantly lower in the
      controlled group. Using patients' overall impression of their asthma control, the
      mean numbers of SABA inhalers purchased were 1.5, 4.4 and 6.4 per year in the
      controlled, partially controlled and uncontrolled groups, respectively (p =
      0.03). Patients' classification of asthma control had better agreement (kappa =
      0.34) with GINA guidelines than physician's' agreement (kappa = 0.05).
      CONCLUSION: When using administrative data for asthma patients, 2 or more SABA
      inhaler purchases in one year should alert the physician for the need for asthma
      control evaluation. Purchase of at least 4 SABA inhalers a year may be regarded
      as a marker for asthma that is not controlled.

PMID- 28759273
TI  - Children with asthma and their caregivers help improve written asthma action
      plans: A pilot mixed-method study.
AB  - OBJECTIVE: The objectives of this study were to (a) qualitatively examine
      caregiver and child feedback about a gold standard written asthma action plan
      (WAAP), and (b) determine whether having an asthma action plan was associated
      with child and caregiver self-efficacy in managing an exacerbation. METHODS: This
      was a cross-sectional analysis of structured interviews with 22 children with
      persistent asthma that collected feedback about the WAAP as well as self
      efficacy. An analysis of interviews used the constant comparative method to
      identify themes of child and caregiver statements. Caregivers completed a
      questionnaire that measured asthma management self-efficacy, barriers to managing
      asthma, and belief in the treatment efficacy using validated scales. RESULTS:
      Approximately 36% of the caregivers reported having a WAAP for their child from
      their child's pediatrician. Most caregivers stated that having pictures would
      improve the WAAP, while most children stated that the layout needed to be
      improved by adding more space between the sections. Caregivers who reported
      knowing what the asthma action plan was had greater self-efficacy than caregivers
      who did not (z = -1.99, p = 0.047). CONCLUSIONS: Re-designing the current WAAP
      layout and including pictures of inhalers may promote patient understanding.
      Future research needs to examine if a re-designed WAAP improves asthma management
      of children with asthma and their caregivers.

PMID- 28759274
TI  - Fractional carbon dioxide laser for facial rejuvenation: A prospective study to
      evaluate the efficacy and the safety.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy and safety of the
      fractional ablative carbon dioxide laser for facial rejuvenation. MATERIALS AND
      METHODS: Twenty-nine female who have the complaint of facial aging were recruited
      for the study. Participants received a maximum of three laser treatment sessions
      with one-month intervals and were scored using a 5-point scale on seven
      categories for facial aging before and after the treatment by the physicians.
      Self-assessments by participants were done at the last month of follow-up period
      and 3 years after the last session. RESULTS: Mean facial aging score before the
      treatment was 11,24 +/- 4,30 and after the treatment was 10,51 +/- 3,86 (p =
      0.003). The decrease in the score was mild in 18 (62,1%) participants, whereas it
      was moderate in only 1 (3,4%) participant. None of the participants had
      significant or perfect improvement. When the seven categories were analyzed
      seperately, the only statistically significant alteration in the score was found
      in the skin tone category (p = 0.0001). CONCLUSION: Results show that
      rejuvenation with the fractional ablative carbon dioxide laser decreases mildly
      the symptoms of facial aging in more than half of the patients.

PMID- 28759275
TI  - Factors associated with depressive symptoms in uncontrolled asthmatics.
AB  - RATIONALE: Recent epidemiological data indicate that approximately 6.7% of US
      adults suffer from depression in any given year. The purpose of the study is to
      identify factors associated with depressive symptoms in a large diverse group of
      patients with poorly controlled asthma. The factors include quality of life
      (QOL), lung function, asthma knowledge, attitudes, self-efficacy, symptoms and
      control of disease. METHODS: Baseline characteristics of a cohort of 599 subjects
      with asthma recruited from twenty Asthma Clinical Research Centers across the
      United States were examined. The Center for Epidemiologic Studies Depression
      Scale (CES-D) was used to stratify subjects into those with depressive symptoms
      (CES-D score >= 16) and those without depressive symptoms (CES-D < 16). Bivariate
      statistics were used to compare the two groups; additionally, logistic regression
      was used to determine factors that have the greatest association with depressive
      symptoms. RESULTS: Subjects with depressive symptoms had significantly lower QOL
      scores and less knowledge about their disease than subjects with no depression;
      however, lung function (FEV1%) and asthma control were not significantly
      associated with depressive symptoms in the logistic regression analysis. Subjects
      who were non-white had lower household income, high school diploma or less, and
      those who were unemployed or disabled had significantly higher scores for
      depressive symptoms. CONCLUSION: Subjects with depressive symptoms have
      significantly less knowledge of their disease and poorer QOL compared to those
      without depressive symptoms. Evaluating depressive symptoms in subjects with
      asthma will provide a more complete picture of their overall condition. The role
      of asthma education on depressive symptoms in this population needs to be further
      investigated. The effect of QOL on treating depression in asthma patients also
      needs to be studied.

PMID- 28759276
TI  - Biochemical and Histopathological Evidence on Beneficial Effects of Standardized
      Extract from Tragopogon graminifolius as a Dietary Supplement in Fatty Liver:
      Role of Oxidative Stress.
AB  - Nonalcoholic fatty liver disease (FLD) is a worldwide common liver disorder.
      Tragopogon graminifolius is used as a dietary supplement for liver disorders.
      This study aimed to assess the beneficial effects of a standardized preparation
      from T. graminifolius extract (TGE) in animal model of FLD induced by high-fat
      diet (HFD). The standardization of TGE based on phenolic compounds was performed
      using high-performance liquid chromatography (HPLC) analysis. The HFD induced
      metabolic and hepatic damages. TGE significantly reduced the elevations of serum
      triglyceride, cholesterol, low-density lipoprotein (LDL), and hepatic enzymes (p
      =.001 for 25, 50, and 100 mg/kg of TGE). Histopathological studies also confirmed
      beneficial effects of TGE in FLD. Activity of total antioxidant power, content of
      total thiol, myeloperoxidase (MPO) enzyme activity, and lipid peroxidation were
      significantly improved (p <.001). Dietary supplementation with TGE results in
      improvement of biochemical as well as histopathological parameters. Clinical
      trials are warranted to prove its efficacy and tolerability in patients with FLD.

PMID- 28759277
TI  - The Experience of Decision Making in the Care of Children with Palliative Care
      Needs: The Experiences of Jordanian Mothers.
AB  - The purpose of this study was to explore the experience of decision making in the
      care of children with palliative care needs in Jordan, from the perspective of
      their mothers. This study employed a collective qualitative case study approach.
      Data were collected in 3 pediatric wards in a Jordanian hospital. The study used
      2 data collection methods: participant observation (197 observational hours) and
      56 semi-structured interviews with 24 mothers, 12 physicians and 20 nurses. The
      findings show how Jordanian mothers seek to transfer the role of decision making
      to physicians, as they perceive themselves to be unable to make decisions about
      critical issues related to the treatment of their children. Mothers had a
      widespread apprehension of "future guilt," especially when they feared that any
      decisions they might make could have an adverse impact on their children.
      Contrary to the predominant pattern, some mothers took a proactive approach
      towards decision making about their children's treatment. These mothers requested
      detailed information from primary physicians and sought different sources of
      knowledge such as second opinions, reading online resources, or talking to other
      parents who had a child with similar circumstances. The study concludes that
      mothers prefer to involve physicians in decisions about their children's
      healthcare and treatment to eliminate their fear of probable future guilt; this
      modifies any tendency to autonomously decide for their children. These findings
      are underpinned by the Jordanian culture in which doctors' opinions are highly
      regarded.

PMID- 28759278
TI  - A cost-effectiveness threshold analysis of a multidisciplinary structured
      educational intervention in pediatric asthma.
AB  - OBJECTIVE: Asthma educational interventions have been shown to improve several
      clinically and economically important outcomes. However, these interventions are
      costly in themselves and could lead to even higher disease costs. A cost
      effectiveness threshold analysis would be helpful in determining the threshold
      value of the cost of educational interventions, leading to these interventions
      being cost-effective. The aim of the present study was to perform a cost
      effectiveness threshold analysis to determine the level at which the cost of a
      pediatric asthma educational intervention would be cost-effective and cost
      saving. METHODS: A Markov-type model was developed in order to estimate costs and
      health outcomes of a simulated cohort of pediatric patients with persistent
      asthma treated over a 12-month period. Effectiveness parameters were obtained
      from a single uncontrolled before-and-after study performed with Colombian
      asthmatic children. Cost data were obtained from official databases provided by
      the Colombian Ministry of Health. The main outcome was the variable "quality
      adjusted life-years" (QALYs). RESULTS: A deterministic threshold sensitivity
      analysis showed that the asthma educational intervention will be cost-saving to
      the health system if its cost is under US$513.20. Additionally, the analysis
      showed that the cost of the intervention would have to be below US$967.40 in
      order to be cost-effective. CONCLUSIONS: This study identified the level at which
      the cost of a pediatric asthma educational intervention will be cost-effective
      and cost-saving for the health system in Colombia. Our findings could be a useful
      aid for decision makers in efficiently allocating limited resources when planning
      asthma educational interventions for pediatric patients.

PMID- 28759280
TI  - Breastfeeding duration is inversely associated with asthma in Japanese children
      aged 3 years.
AB  - OBJECTIVE: Recent meta-analyses found an inverse relationship between
      breastfeeding duration and asthma in children. The present cross-sectional study
      investigated the associations between breastfeeding duration and the prevalence
      of wheeze and asthma in Japanese children aged 3 years. METHODS: Subjects were
      6412 children who participated in the Kyushu Okinawa Child Health Study. Data
      were collected using a self-administered questionnaire. Wheeze was defined
      according to the criteria of the International Study of Asthma and Allergies in
      Childhood. Asthma was considered present if the child had been diagnosed by a
      physician as having asthma. Associations of breastfeeding duration with wheeze
      and asthma were estimated using multivariate generalized estimating equation
      methods adjusted for maternal, family, and health characteristics. RESULTS: The
      prevalence values of wheeze and asthma were 19.5% and 7.0%, respectively.
      Compared with <4 months of exclusive breastfeeding, exclusive breastfeeding for
      >=4 months was not significantly associated with wheeze or asthma. Compared with
      <10 months of breastfeeding duration regardless of exclusivity, 10 to <14 months,
      14 to <19 months, and 19 months or more of breastfeeding duration regardless of
      exclusivity were independently inversely related to asthma: the adjusted odds
      ratios [ORs; 95% confidence intervals (CIs)] were 0.69 (0.52-0.91, p = 0.01),
      0.73 (0.56-0.97, p = 0.03), and 0.67 (0.51-0.88, p = 0.004), respectively. No
      association was found between breastfeeding duration regardless of exclusivity
      and wheeze. CONCLUSIONS: We confirmed an inverse association between
      breastfeeding duration regardless of exclusivity and asthma.

PMID- 28759279
TI  - Smokers who have children with asthma: Perceptions about child secondhand smoke
      exposure and tobacco use initiation and parental willingness to participate in
      child-focused tobacco interventions.
AB  - OBJECTIVE: This study examined, among parents who smoke and have children with
      asthma, perceptions about child secondhand smoke exposure (SHSe), child tobacco
      use (TU) initiation, and parent willingness to participate in child-focused
      tobacco interventions. METHODS: Participants were 300 caregivers who smoked and
      had a child with asthma (aged 10-14). Parents completed an online survey and self
      reported perceptions about child SHSe elimination, child TU prevention, and
      willingness to participate in three types of interventions with and without their
      child (SHSe reduction intervention, tobacco prevention intervention, and the
      combination of the two). Correlates of perceptions and willingness were examined.
      RESULTS: Parents who were ready to quit smoking and who reported home smoking
      bans (HSBs) were more motivated to eliminate SHSe (p < 0.05). Being white,
      younger, ready to quit, and having HSBs were associated with greater confidence
      to eliminate SHSe (p < 0.05). Parents with HSBs reported higher perceived
      importance about preventing child TU (p < 0.05). Parents were less confident
      about preventing male children from using tobacco (p = 0.001). Parents were
      highly willing to participate in all the described intervention approaches, with
      or without their child. CONCLUSIONS: Parents were willing to participate in child
      focused tobacco interventions, with or without their child with asthma, including
      interventions that address both child SHSe and TU prevention. This research
      demonstrates the acceptability of child-focused tobacco interventions among a
      high-risk population and may be a foundational step for intervention development.

PMID- 28759282
TI  - Adolescent Risk Screening Instruments for Primary Care: An Integrative Review
      Utilizing the Donabedian Framework.
AB  - Adolescent risk-taking behavior choices can affect future health outcomes. The
      purpose of this integrative literature review is to evaluate adolescent risk
      screening instruments available to primary care providers in the United States
      using the Donabedian Framework of structure, process, and outcome. To examine the
      literature concerning multidimensional adolescent risk screening instruments
      available in the United States for use in the primary care setting, library
      searches, ancestry searches, and Internet searches were conducted. Library
      searches included a systematic search of the Cumulative Index to Nursing and
      Allied Health Literature (CINAHL), Academic Search Premier, Health Source Nursing
      Academic Ed, Medline, PsycINFO, the Psychology and Behavioral Sciences
      Collection, and PubMed databases with CINAHL headings using the following Boolean
      search terms: "primary care" and screening and pediatric. Criteria for inclusion
      consisted of studies conducted in the United States that involved broad
      multidimensional adolescent risk screening instruments for use in the pediatric
      primary care setting. Instruments that focused solely on one unhealthy behavior
      were excluded, as were developmental screens and screens not validated or
      designed for all ages of adolescents. In all 25 manuscripts reviewed, 16 screens
      met the inclusion criteria and were included in the study. These 16 screens were
      examined for factors associated with the Donabedian structure-process-outcome
      model. This review revealed that many screens contain structural issues related
      to cost and length that inhibit provider implementation in the primary care
      setting. Process limitations regarding the report method and administration
      format were also identified. The Pediatric Symptom Checklist was identified as a
      free, short tool that is valid and reliable.

PMID- 28759281
TI  - Balanced Caloric Restriction Minimizes Changes Caused by Aging on the Colonic
      Myenteric Plexus.
AB  - Aging can promote significant morphofunctional changes in the gastrointestinal
      tract (GIT). Regulation of GIT motility is mainly controlled by the myenteric
      neurons of the enteric nervous system. Actions that aim at decreasing the aging
      effects in the GIT include those related to diet, with caloric restriction (CR).
      The CR is achieved by controlling the amount of food or by manipulating the
      components of the diet. Therefore, the objective of this study was to evaluate
      different levels of CR on the plasticity of nicotinamide adenine dinucleotide
      phosphate- (NADPH-) reactive myenteric neurons in the colon of Wistar rats during
      the aging process using ultrastructural (transmission electron microscopy) and
      morphoquantitative analysis. Wistar male rats (Rattus norvegicus) were
      distributed into 4 groups (n = 10/group): C, 6-month-old animals; SR, 18-month
      old animals fed a normal diet; CRI, 18-month-old animals fed a 12% CR diet; CRII,
      18-month-old animals fed a 31% CR diet. At 6 months of age, animals were
      transferred to the laboratory animal facility, where they remained until 18
      months of age. Animals of the CRI and CRII groups were submitted to CR for 6
      months. In the ultrastructural analysis, a disorganization of the periganglionar
      matrix with the aging was observed, and this characteristic was not observed in
      the animals that received hypocaloric diet. It was observed that the restriction
      of 12.5% and 31% of calories in the diet minimized the increase in density and
      cell profile of the reactive NADPH neurons, increased with age. This type of diet
      may be adapted against gastrointestinal disturbances that commonly affect aging
      individuals.

PMID- 28759283
TI  - Parental Concern: Parents Discuss How They Support Their Adolescents Attending
      Schoolies Events in Australia.
AB  - Adolescents who have completed their high school studies converge on coastal
      areas of Australia annually to celebrate their freedom in events known as
      "Schoolies." The current body of research in relation to Schoolies demonstrates
      that adolescents consume alcohol and other drugs and engage in sexual activity
      during these events. Exactly how parents support adolescents in attending these
      events and how they perceive the Schoolies experience represent major gaps in the
      literature. To undertake this research, 7 parents were interviewed using a semi
      structured approach. Interview transcripts were analyzed using Braun and Clarke's
      thematic analysis, with 4 main themes identified: communication, consuming
      alcohol, peer support, and helping parents to support their adolescents in
      attending Schoolies. Communication was the main strategy used by parents to talk
      about Schoolies with their adolescent, with the majority encouraging open
      communication around drinking alcohol, staying with friends, and instilling
      correct or moral values into their adolescents in relation to respectful
      behavior. Parents saw the consumption of alcohol as inevitable and as something
      they could not control. However, the ramifications of alcohol consumption were
      the primary concerns for these parents. This study provides a number of insights
      into the perceptions that parents have about Schoolies events and how they
      support their adolescent to attend. Parents sought guidance in supporting their
      adolescent child via educational media and talking to other parents.

PMID- 28759284
TI  - Effectiveness of cognitive behavioural therapy in reducing anxiety in adults and
      children with asthma: A systematic review.
AB  - OBJECTIVE: Asthma and anxiety are known to interact, leading to exacerbations for
      both conditions. This systematic review summarised evidence regarding the
      effectiveness of cognitive behavioural therapy (CBT) in reducing anxiety in
      individuals with asthma, with results presented separately for adults and
      children. DATA SOURCES: PRISMA and CRD guidance were followed to conduct and
      report the current review. Three major electronic databases (Ovid Medline,
      PsycINFO, and EMBASE) and manual searches were used to find relevant published
      and unpublished research. STUDY SELECTIONS: Sixteen trials (12 adult- and four
      child-focused) met inclusion criteria, and were evaluated with adapted quality
      criteria. Both controlled trials and repeated-measures designs were eligible. All
      CBT intervention formats were eligible (group, individual, computerised, and self
      help). Nine studies (eight adult and one child) focused upon participants with
      either an anxiety diagnosis or with above-threshold anxiety scores on a validated
      measure at baseline. RESULTS: The review provides tentative preliminary support
      for the use of CBT for anxiety in adults with asthma, with the evidence base for
      interventions with children appearing promising, but under-developed. Studies
      were more likely to indicate beneficial effects where anxiety-focused (rather
      than illness-focused) intervention protocols were utilised, asthma-related
      education was provided and where the trials focused on individuals with likely
      clinical levels of anxiety at baseline. CONCLUSION: Whilst further high-quality
      research is needed, available evidence is supportive of anxiety-focused CBT
      interventions tailored to target the particular mechanisms thought to maintain
      this comorbidity in asthma.

PMID- 28759285
TI  - Systematic review and content analysis of asthma knowledge questionnaires: A
      focus on the knowledge surrounding acute exacerbation management.
AB  - OBJECTIVES: Asthma education is a key component of asthma management. Asthma
      education around the management of a person who is having an acute exacerbation
      of asthma (often referred to as asthma first aid (AFA) training) is important,
      particularly in a school setting. There is no gold standard assessment of asthma
      knowledge and also there is no specific tool to measure the knowledge of AFA. Our
      aim was to identify asthma knowledge questionnaires and perform a content
      analysis. We were interested in evaluating the number, the type and the format of
      AFA questions. METHOD: A literature search was performed to identify the
      instruments which were able to assess asthma knowledge of people with asthma
      and/or caregivers of people with asthma. An electronic database search was
      performed in EMBASE, IPA, MEDLINE and PUBMED. Articles which described the
      development or psychometric testing of an asthma knowledge questionnaire were
      included. The content of questions in each instrument was analysed and
      categorised using the NVivo software, and a secondary analysis was performed to
      identify knowledge questions relevant to the management of an acute asthma
      exacerbation. RESULTS: Forty-four papers with 37 different instruments met the
      inclusion criteria. The majority of the instruments contained a relatively low
      proportion of questions related to the management of acute asthma, i.e., only 162
      of the 780 questions (21%). No questionnaire had sufficient specific emphasis on
      acute asthma management knowledge to test the impact of AFA training. CONCLUSION:
      There is a scope to develop an up-to-date validated acute asthma management
      knowledge questionnaire for use in research and clinical settings.

PMID- 28759286
TI  - Influence of electrodes on the 448 kHz electric currents created by
      radiofrequency: A finite element study.
AB  - Radiofrequency is a technology used in physical rehabilitation by physicians and
      physiotherapists for more than fifteen years, although there exist doubts on how
      it works. Indiba is a particular method that applies a voltage difference of 448
      KHz between two electrodes, creating an electric current between them. These
      electrodes are an active one that is placed on different areas of the body and a
      passive one that is left on the same position during the treatment. There are two
      different types of active electrodes: the capacitive one and the resistive one.
      In this paper, it has been studied how the different electrodes affect the
      current density inside the body and thus how they affect the efficacy of the
      treatment. It shows how finite element calculations should help physicians in
      order to better understand its behavior and improve the treatments.

PMID- 28759287
TI  - The use of platelet-rich plasma to treat chronic tendinopathies: A technical
      analysis.
AB  - Platelet-rich plasma (PRP) is blood plasma with a high concentration of
      autologous platelets which constitute an immense reservoir of growth factors. The
      clinical use of PRP is widespread in various medical applications. Although
      highly popular with athletes, the use of PRP for the treatment of tendinopathies
      remains scientifically controversial, particularly due to the diversity of
      products that go by the name of "PRP." To optimize its use, it is important to
      look at the various stages of obtaining PRP. In this literature review, we take a
      closer look at eight parameters which may influence the quality of PRP: 1)
      anticoagulants used to preserve the best platelet function, 2) the speed of
      centrifugation used to extract the platelets, 3) the platelet concentrations
      obtained, 4) the impact of the concentration of red and while blood cells on PRP
      actions, 5) platelet activators encouraging platelet degranulation and, hence,
      the release of growth factors, and 6) the use or nonuse of local anesthetics when
      carrying out infiltration. In addition to these parameters, it may be interesting
      to analyze other variables such as 7) the use of ultrasound guidance during the
      injection with a view to determining the influence they have on potential
      recovery.

PMID- 28759288
TI  - Neurological Imaging in Acquired Cranial Nerve Palsy: Ophthalmologists vs.
      Neurologists.
AB  - PURPOSE: Cranial nerve palsies often require neurological imaging by MRI.
      Guidelines on whether or not to utilize MRI have been absent or lack clarity. In
      daily practice, both neurologists and ophthalmologists treat patients with
      cranial nerve palsy and determine whether neuro-imaging is required. There appear
      to be differences in policy with respect to neuro-imaging. The question, which
      will be answered in this study, is the following: to what extent do differences
      in policy exist between ophthalmologists and neurologists regarding imaging by
      MRI of patients with acquired ocular cranial nerve palsy? METHOD: PubMed database
      was searched for literature on acquired cranial nerve palsy and MRI scanning
      performed by ophthalmologists and neurologists. Case series published between
      2000 and 2015 were included. The first author screened the literature on
      eligibility, profession of the authors, and conducted data abstraction. RESULT:
      Ten case series were found eligible for analysis. A total of 889 cranial nerve
      palsies were described, 770 by ophthalmologists and 119 by neurologists. The age
      range of patients in all case series was 2 to 96 years of age. The oculomotor
      nerve was investigated in 162 patients, the trochlear nerve in 131 patients, and
      the abducens nerve in 486 patients. All neurologists (n=3) and 2 out of 7
      investigated ophthalmologists recommended performing MRI scanning in every
      patient who presented with an ocular cranial nerve palsy, while 5
      ophthalmologists (5/7) opted to triage patients for risk factors associated with
      cranial nerve palsies prior to ordering MRI imaging. When different groups of
      patients were viewed separately, it became apparent that almost all specialists
      agreed that every patient with a third nerve palsy and patients under 50 years of
      age should undergo MRI scanning. In patients with fourth nerve palsy, MRI
      scanning was not indicated. CONCLUSION: The neurologists in this study were more
      likely to perform MRI scanning in every patient presenting with ocular cranial
      nerve palsy. Ophthalmologists were more likely to determine risk factors
      associated with cranial nerve palsy, which they took into account when deciding
      whether or not to perform neurological imaging in patients aged more than 50
      years or presenting with abducens nerve palsy.

PMID- 28759289
TI  - Treatment of pseudoxanthoma elasticum-like papillary dermal elastolysis with
      nonablative fractional resurfacing laser resulting in clinical and histologic
      improvement in elastin and collagen.
AB  - OBJECTIVE: Pseudoxanthoma elasticum-like papillary dermal elastolysis (PXE-PDE)
      is a rare skin condition seen predominantly in elderly females. These
      asymptomatic lesions are brought to the dermatologist's attention due to
      patient's displeasure in their appearance. We report a case of a 28-year-old
      female with PXE-PDE on the right neck treated with nonablative fractional
      resurfacing (NAFR). CASE: The patient on examination had yellow-to-skin-colored
      papules that coalesced into a cobblestone-appearing plaque on her lateral neck.
      The area was treated with NAFR to improve texture and cosmesis. After three
      treatments, the patient noted at least a 50% improvement of appearance and
      texture in the affected skin. Adverse effects were mild without development of
      serious side effects, such as scarring and/or permanent dyspigmenation.
      CONCLUSION: Established therapies for elastin disorders like PXE-PDE have yielded
      unsatisfactory results by patient and clinician standards. Positive results with
      NAFR, illustrated in our PXE-PDE case, further provides a role for NAFR in
      elastin disorders.

PMID- 28759290
TI  - High Dose Vitamin D Supplementation Is Associated With a Reduction in Depression
      Score Among Adolescent Girls: A Nine-Week Follow-Up Study.
AB  - Although vitamin D deficiency is known to be a risk factor for some psychological
      disorders, there have been few studies on the effects of vitamin D
      supplementation on their symptoms. Depression and aggression are common mental
      disorders and are associated with disability and disease burden. We aimed to
      evaluate the effectiveness of high-dose vitamin D supplementation on depression
      and aggression scores in adolescent girls. Nine hundred forty adolescent girls
      received vitamin D3 at a dose of 50,000 IU/week for 9 weeks. Anthropometric
      parameters and blood pressure were measured using standard protocols at the
      baseline and at the end of the study. Depression score was evaluated using the
      Beck Depression Inventory-II and aggression was evaluated using the Buss-Perry
      Aggression Questionnaire at baseline and at the end of the study. Comparison
      among the four categories of depression score (normal, mild, moderate, and
      severe) revealed no significant differences in demographic and anthropometric
      parameters at baseline. After 9 weeks of vitamin D supplementation, there was a
      significant reduction on mild, moderate, and severe depression score. However,
      vitamin D supplementation had no significant effect on aggression score. Our
      results suggest that supplementation with vitamin D may improve depressive
      symptoms among adolescent girls, as assessed by questionnaire, but not aggression
      score. Formal, larger, randomized controlled studies are required to confirm this
      effect on cases with different degrees of depression.

PMID- 28759291
TI  - Years of life lost due to bronchial asthma in Poland between 1999 and 2013.
AB  - OBJECTIVE: The aim of this study was to analyze the years of life lost due to
      asthma in Poland between 1999 and 2013, with the use of the SEYLL measure
      (Standard Expected Years of Life Lost). METHODS: The study was based on a dataset
      of 5,606,516 records gathered from death certificates of Polish residents from
      1999 to 2013. The data on the deaths due to bronchial asthma and status
      asthmaticus (J45 and J46 according to ICD-10) were used for the analysis. The
      SEYLL, SEYLLp (SEYLL per person) and SEYLLd (SEYLL per death) were implemented to
      assess lost life years. The analysis of time trends was performed with the use of
      the join point model. RESULTS: In 1999-2013, asthma and status asthmaticus were
      the cause of 11,380 deaths of Poles (0.20% of all deaths), resulting in 4.23
      prematurely lost life years per 10,000 males and 3.22 years per 10,000 females.
      Over the analyzed years, the value of SEYLL decreased both for men and women.
      Every man who died due to bronchial asthma in Poland in the studied period, lost
      on average 19.12 years of life, and every woman 18.20 years. CONCLUSIONS: The
      analysis of SEYLL indicated that premature mortality due to asthma is still a
      meaningful problem in the Polish population and a constant challenge for public
      health activities.

PMID- 28759292
TI  - An Optimal Measurement of Fixation Disparity Using Ogle's Apparatus.
AB  - PURPOSE: Fixation disparity (FD) is a small misalignment of the eyes within the
      normal alignment when viewing under binocular condition. Ogle's apparatus
      measures FD. Standards of procedures vary, which may lead to different outcomes.
      METHODS: Students with normal ocular alignment, stereopsis <=60 seconds of arc
      and visual acuity <0.1 logMAR, were included in this prospective comparative
      study. Four procedures (P1-P4) of measuring FD with Ogle's apparatus were
      performed with divergent placement of the line (P1 and P3), or the line moving
      from subjective zero (P1 and P2: prisms of ascending strength; P3 and P4: prisms
      alternating base in base out; combined and P4). Differences in the FD curve were
      determined by looking at point zero, motor fusion amplitude, and the degree of
      FD. RESULTS: Twenty-six participants were examined by these 4 procedures. Point
      zero showed a significant difference between P1-P2 (P=0.006) and P3-P4 (P=0.001).
      P1 and P3 indicated the highest point zero: median of -1 and -1.5 minutes of arc
      exodisparity. Motor fusion amplitude showed a significant difference between P1
      P2 (P=0.037), P1-P3 (P=0.004), and P2-P4 (P=0.002). P1 revealed the highest motor
      fusion amplitude (median of 34Delta) and P4 the lowest amplitude (median of
      28Delta). No significant differences were found in esodisparity. In exodisparity
      there was a significant difference comparing P1-P2 (P=0.000), P3-P4 (P=0.000),
      and P1-P3 (P=0.021). P1 gave the highest exodisparity (median 22 minutes of arc)
      and P4 the lowest (median 10 minutes of arc). CONCLUSION: Clinically relevant
      differences were found in exodisparity, mainly caused by difference in line
      shifting. Exodisparity was significantly lower, moving the line from subjective
      zero. The most accurate procedure is using prisms of ascending strength combined
      with divergent placement of the line (P1). These findings standardize a reliable
      procedure of measuring the FD curve for clinical use. Patients will not be
      misdiagnosed with reduced FD.

PMID- 28759293
TI  - Superior and Lateral Rectus Myopexy for Acquired Adult Distance Esotropia: A "One
      Size Fits All" Surgery.
AB  - AIM: To evaluate the results of bilateral lateral rectus to superior rectus
      myopexy for the treatment of acquired adult distance esotropia. METHODS: The
      charts of all adult patients who were operated for esotropia by the first author
      at the Department of Ophthalmology, Assaf Harofeh Medical Center, Tel Aviv
      University, Zrifin, Israel, between the years 2010-2015 were analyzed. Patients
      with the following inclusion criteria were included: acquired esotropia (not
      present during childhood); deviation greater for distance than near by at least 4
      prism diopters (PD); slight abduction deficit in one or both eyes and/or
      displacement of the lateral rectus downwards as evident by CT/MRI with or without
      superior rectus nasal shift and no neurologic abnormalities such as cranial nerve
      palsies or other. RESULTS: Eighteen patients were identified (age 31-80 years,
      mean 49.6 years, 77.7% females). Pre-operative esodeviation averaged 24.3 PD
      (range 14-35 PD) for distance and 15.7 PD (range 8-25 PD) for near. Thirteen
      patients (72%) had diplopia. All patients were myopic (average -5.54 diopters,
      range -2.00 to -13.00). All patients underwent bilateral superior rectus-lateral
      rectus myopexy. Seven patients needed additional single medial rectus recession
      of between 2-6 mm, and two had additional inferior rectus recession. After a
      follow-up period of 3-52 months (average 16 months), 16/18 patients (88%) had a
      deviation less than 5 PD. No overcorrections were noted. CONCLUSION: Lateral to
      superior rectus myopexy is a safe and effective treatment for patients with
      distance esotropia in which displacement of these muscles is identified.
      Additional single medial rectus and/or inferior rectus recession may be needed in
      some patients.

PMID- 28759295
TI  - Preventing Discontinuation of Radiation Therapy: Predictive Factors to Improve
      Patient Selection for Palliative Treatment.
AB  - PURPOSE: Approximately one third of patients with cancer require palliative
      radiation therapy (PRT), yet no guidelines exist for optimal patient selection.
      We have observed that many patients who begin PRT do not complete their
      prescribed treatment. Our study sought to identify factors associated with
      discontinuation of PRT, assess for a relationship with survival, and inform
      patient selection. METHODS: We performed an institutional review board-approved
      retrospective analysis of patients with cancer treated in a multicenter radiation
      oncology department in 2014. Of 297 patients who began PRT, 60 discontinued and
      237 completed treatment. Primary end points included discontinuation and overall
      survival. RESULTS: Patient factors were analyzed for association with
      discontinuation of PRT and overall survival, respectively, using logistic
      regression and Cox proportional regression models. Factors associated with
      discontinuation were low Karnofsky performance status (KPS) score, high number of
      fractions prescribed, and treatment site other than bone metastasis. The odds of
      discontinuing PRT decreased by approximately 52% for every 10-point increase in
      KPS score (odds ratio, 0.48; 95% CI, 0.36 to 0.63; P < .001). Factors associated
      with shorter survival included discontinuation of PRT, low KPS score, community
      practice location, multiple comorbidities, and treatment of brain metastases.
      Patients who discontinued treatment were more likely to die than patients who
      completed treatment, independent of other factors (hazard ratio, 3.67; 95% CI,
      2.41 to 5.61; P < .001). CONCLUSION: Patients with low KPS scores, long treatment
      courses, and those treated to sites other than bone metastasis were significantly
      more likely to discontinue treatment. Discontinuation was predictive for poor
      survival. Pretreatment evaluation of KPS, comorbidities, and brain metastases can
      help guide appropriate patient selection for PRT.

PMID- 28759294
TI  - Epidermal Growth Factor Receptor activation promotes ADA3 acetylation through the
      AKT-p300 pathway.
AB  - The ADA3 (Alteration/Deficiency in Activation 3) protein is an essential adaptor
      component of several Lysine Acetyltransferase (KAT) complexes involved in
      chromatin modifications. Previously, we and others have demonstrated a crucial
      role of ADA3 in cell cycle progression and in maintenance of genomic stability.
      Recently, we have shown that acetylation of ADA3 is key to its role in cell cycle
      progression. Here, we demonstrate that AKT activation downstream of Epidermal
      Growth Factor Receptor (EGFR) family proteins stimulation leads to
      phosphorylation of p300, which in turn promotes the acetylation of ADA3.
      Inhibition of upstream receptor tyrosine kinases (RTKs), HER1 (EGFR)/HER2 by
      lapatinib and the accompanying reduction of phospho-AKT levels led to a decrease
      in p300 phosphorylation and ADA3 protein levels. The p300/PCAF inhibitor garcinol
      also destabilized the ADA3 protein in a proteasome-dependent manner and an ADA3
      mutant with K->R mutations exhibited a marked increase in half-life, consistent
      with opposite role of acetylation and ubiquitination of ADA3 on shared lysine
      residues. ADA3 knockdown led to cell cycle inhibitory effects, as well as
      apoptosis similar to those induced by lapatinib treatment of HER2+ breast cancer
      cells, as seen by accumulation of CDK inhibitor p27, reduction in mitotic marker
      pH3(S10), and a decrease in the S-phase marker PCNA, as well as the appearance of
      cleaved PARP. Taken together our results reveal a novel RTK-AKT-p300-ADA3
      signaling pathway involved in growth factor-induced cell cycle progression.

PMID- 28759296
TI  - Potential Role of L-Arginine and Vitamin E Against Bone Loss Induced by Nano-Zinc
      Oxide in Rats.
AB  - The purpose of this study was to illustrate the effects of zinc oxide
      nanoparticles (ZnO-NPs) administration on bone turnover and bone resorbing agents
      in rats and how L-arginine (L-arg) or vitamin E (vit E) co-administrations might
      affect them. Fasting rats were randomly divided into four groups (n = 10): G1
      normal healthy animals; G2-ZnO-NPs-exposed rats (600 mg/kg-1/day-1); G3-ZnO-NPs
      exposed rats co-administrated L-arg (200 mg/kg-1/day-1); G4-ZnO-NPs-exposed rats
      co-administrated vit E (200 mg/kg-1/day-1). The ingredients were orally
      administered daily. The body weight and food consumption of rats were recorded
      during the administration period and the experiment continued for three
      consecutive weeks. The results demonstrated that ZnO-NPs administration induced
      bone loss in rats as manifested by reduced activity of bone alkaline phosphatase
      (B-ALP) and increased level of C-terminal peptide type I collagen (CTx). The
      increase of inflammatory markers, tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) by ZnO-NPs suggests that deleterious effects of ZnO-NPs on
      bone turnover were, in part, due to inflammation. Confirming to this suggestion,
      both L-arg and vit E reduced TNF-alpha and IL-6 levels and consequently decreased
      bone resorption as indicated by reduced serum CTx level. This study proved that
      ZnO-NPs can induce bone turnover, which may be reduced by L-arg or vit.E co
      administration, partly by anti-inflammatory mechanism.

PMID- 28759297
TI  - Self-assembling anticaries mucosal vaccine containing ferritin cage nanostructure
      and glucan-binding region of S. mutans glucosyltransferase effectively prevents
      caries formation in rodents.
AB  - Anticaries protein vaccines that induce a mucosal immune response are not
      effective. Therefore, development of effective and convenient anticaries vaccines
      is a priority of dental research. Here we generated self-assembling nanoparticles
      by linking the glucan-binding region of Streptococcus mutans glucosyltransferase
      (GLU) to the N-terminal domain of ferritin to determine whether these novel
      nanoparticles enhanced the immunogenicity of an anticaries protein vaccine
      against GLU in rodents. We constructed the expression plasmid pET28a-GLU-FTH and
      purified the proteins from bacteria using size-exclusion chromatography. BALB/c
      mice were used to evaluate the ability of GLU-ferritin (GLU-FTH) nanoparticles to
      induce GLU-specific mucosal and systemic responses. The protective efficiency of
      GLU-FTH nanoparticles was compared with that of GLU alone or a mixture of GLU and
      poly(I:C) after administering an intranasal infusion to Wistar rats. The
      phagocytosis and maturation of dendritic cells (DCs) exposed in vitro to the
      nanoparticles were assessed using flow cytometry. The GLU-FTH nanoparticle
      vaccine elicited significantly higher levels of GLU-specific antibodies compared
      with GLU or a mixture of GLU and poly(I:C). Immunization with GLU-FTH achieved
      lower caries scores compared with those of the other vaccines. Administration of
      GLU-FTH nanoparticles enhanced phagocytosis by DCs and their maturation. Thus,
      self-assembling GLU-FTH is a highly effective anticaries mucosal vaccine that
      enhanced antibody production and inhibited S. mutans infection in rodents.

PMID- 28759298
TI  - Fusional Amplitudes: Developing Testing Standards.
AB  - PURPOSE: The stability of binocular vision depends upon good fusional amplitudes,
      but the clinical assessment of fusional amplitudes varies around the world. The
      purpose of this study was to determine whether or not there is variation in the
      assessment of fusional amplitudes in normal subjects. The author looked at the
      testing distance, the order of testing, the role of examiner encouragement, and
      the subject's level of alertness. METHODS: In a prospective study using a
      modified crossover design, the author assessed fusional amplitudes in 99 subjects
      with normal eye exams. The measurements were done in two separate sessions on
      different days with each subject being randomized as to the order of fusional
      vergence testing. All subjects were assessed without and with encouragement in
      the first session. In the second session, all were assessed at different testing
      distances. RESULTS: The author previously presented data on 50 subjects. In this
      expanded cohort, statistical significance was reached confirming the previous
      findings that convergence is significantly affected by encouragement, divergence
      is significantly reduced if assessed after convergence, and near amplitudes are
      significantly higher than distance amplitudes. Finally, there is a negative
      correlation between age and convergence break point. CONCLUSIONS: The results of
      this study demonstrate that divergence is significantly reduced if assessed after
      convergence in the subject with normal binocular function. Next, convergence is
      significantly affected by the use of encouragement. Measurements at near produced
      significantly higher results for all of the convergence and divergence tests.
      Finally, there is a significant negative correlation between age and convergence
      break point. We need to develop a standard of testing fusional amplitudes so
      there is consistency in the clinical assessment.

PMID- 28759299
TI  - International Practice in Care Provision for Post-stroke Visual Impairment.
AB  - PURPOSE: This study sought to explore the practice of orthoptists internationally
      in care provision for poststroke visual impairment. METHODS: Survey questions
      were developed and piloted with clinicians, academics, and users. Questions
      addressed types of visual problems, how these were identified, treated, and
      followed up, care pathways in use, links with other professions, and referral
      options. The survey was approved by the institutional ethical committee. The
      survey was accessed via a web link that was circulated through the International
      Orthoptic Association member professional organisations to orthoptists. RESULTS:
      Completed electronic surveys were obtained from 299 individuals. About one-third
      (35.5%) of orthoptists saw patients within 2 weeks of stroke onset and over half
      (55.5%) by 1 month post stroke. Stroke survivors were routinely assessed by 87%;
      over three-quarters in eye clinics. Screening tools were used by 11%. Validated
      tests were used for assessment of visual acuity (76.5%), visual field (68.2%),
      eye movement (80.9%), binocular vision (77.9%), and visual function (55.8%).
      Visual problems suspected by family or professionals were high (86.6%). Typical
      overall follow-up period of vision care was less than 3 months. Designated care
      pathways for stroke survivors with visual problems were used by 56.9% of
      orthoptists. Information on visual impairment was provided by 85.9% of
      orthoptists. CONCLUSIONS: In international orthoptic practice, there is general
      agreement on assessment and management of visual impairment in stroke
      populations. More than half of orthoptists reported seeing stroke survivors
      within 1 month of the stroke onset, typically in eye clinics. There was a high
      use of validated tests of visual acuity, visual fields, ocular motility, and
      binocular vision. Similarly there was high use of established treatment options
      including prisms, occlusion, compensatory strategies, and oculomotor training,
      appropriately targeted at specific types of visual conditions/symptoms. This
      information can be used to inform choice of core outcome orthoptic measures in
      stroke practice.

PMID- 28759300
TI  - PAR-1 and PAR-2 Expression Is Enhanced in Inflamed Odontoblast Cells.
AB  - Protease-activated receptors (PARs) are G protein-coupled receptors, which are
      activated by proteolytical cleavage of the amino-terminus and act as sensors for
      extracellular proteases. We hypothesized that PAR-1 and PAR-2 can be modulated by
      inflammatory stimulus in human dental pulp cells. PAR-1 and PAR-2 gene expression
      in human pulp tissue and MDPC-23 cells were analyzed by quantitative polymerase
      chain reaction. Monoclonal PAR-1 and PAR-2 antibodies were used to investigate
      the cellular expression of these receptors using Western blot, flow cytometry,
      and confocal microscopy in MDPC-23 cells. Immunofluorescence assays of human
      intact and carious teeth were performed to assess the presence of PAR-1 and PAR-2
      in the dentin-pulp complex. The results show for the first time that human
      odontoblasts and MDPC-23 cells constitutively express PAR-1 and PAR-2. PAR-2
      activation increased significantly the messenger RNA expression of matrix
      metalloproteinase (MMP)-2, MMP-9, MMP-13, and MMP-14 in MDPC-23 cells ( P <
      0.05), while the expression of these enzymes decreased significantly in the PAR-1
      agonist group ( P < 0.05). The high-performance liquid chromatography and matrix
      assisted laser desorption/ionization-time-of-flight mass spectrometry analysis
      showed the presence of MMP-13 activity cleaving PAR-1 at specific, noncanonical
      site TLDPRS42?F43LL in human dental pulp tissues. Also, we detected a presence of
      a trypsin-like activity cleaving PAR-2 at canonical site SKGR20?S21LIGRL in pulp
      tissues. Confocal microscopy analysis of human dentin-pulp complex showed intense
      positive staining of PAR-1 and PAR-2 in the odontoblast processes in dentinal
      tubules of carious teeth compared to intact ones. The present results support the
      hypothesis of activation of the upregulated PAR-1 and PAR-2 by endogenous
      proteases abundant during the inflammatory response in dentin-pulp complex.

PMID- 28759301
TI  - A Rare Case: Struma Ovarii in a 14-Year-Old Girl.
AB  - Ovarian tumors presented with ovarian mass in childhood and adolescence are
      uncommon but an important part of gynecological cases. Struma ovarii is one of
      the rare cystic benign ovarian tumors that is observed predominantly in women who
      are between the ages of 40 and 60 years old. It is extremely rare in adolescents.
      Herein, we present a 14-year-old adolescent girl with struma ovarii who presented
      to the emergency room with abdominal pain.

PMID- 28759302
TI  - Evaluation of Clinical Efficacy and Safety of a Novel Cyclosporin A Nanoemulsion
      in the Treatment of Dry Eye Syndrome.
AB  - PURPOSE: Topical administration of the anti-inflammatory agent cyclosporin A
      (CsA) is recommended for long-term management of dry eye syndrome (DES), yet
      standard ophthalmic CsA preparations have been reported to be unstable. In this
      trial, the efficacy and safety of ClacierTM (based on a phase 3 study developed
      by Huons Co. Ltd.), a novel 0.05% CsA nanoemulsion formulation, are compared with
      those of the conventional Restasis(r) emulsion. METHODS: Patients with moderate
      to-severe DES were randomly assigned to receive topical 0.05% CsA in the form of
      Clacier or Restasis, to be administered twice daily for 12 weeks. The primary
      efficacy outcome was the change from baseline in corneal fluorescein staining
      scores at week 12; changes at weeks 4 and 8 were secondary endpoints. Additional
      endpoints included score changes from baseline in nonanesthetic Schirmer's test
      I, tear breakup time, ocular surface disease index, and conjunctival staining.
      RESULTS: At week 12, corneal staining scores were improved in patients treated
      with Clacier and Restasis, with no significant difference between treatments (P =
      0.41). Temporal conjunctival surface damage was significantly more ameliorated
      with Clacier treatment than with Restasis treatment (P = 0.034). Notably, tear
      film stability was improved more rapidly in Clacier patients at week 4 (P =
      0.005) than in Restasis patients (P = 0.36). Improvements in tear production were
      comparable with both Clacier and Restasis treatments. Clacier did not increase
      the risk of adverse events as compared with Restasis. CONCLUSION: Treatment with
      Clacier alleviated clinical signs and symptoms of DES comparably to the
      commercially available Restasis, resulting in improved quality of life for
      patients. Clacier is an effective and safe therapeutic agent for DES.

PMID- 28759303
TI  - Fertility Preservation in Young Female Cancer Patients: Development and Pilot
      Testing of an Online Decision Aid.
AB  - PURPOSE: Impairment of fertility is a common sequela of successful cancer
      treatment. Therefore, fertility preservation (FP) should be discussed with all
      young cancer patients. Decisions about FP are challenging. Patients wish more
      specific support and the first results concerning the helpfulness of decision
      aids (DA) were promising. Aside from describing the process of development and
      the content of an online DA in German, the objective of this study was to pilot
      test users' satisfaction with the DA and its effect on knowledge about FP and
      decisional conflict (DC). METHODS: In this prospective consecutive study, a
      control group (n = 20, fertility counseling) was followed by and compared with an
      intervention group (n = 20, counseling and additional use of the DA, developed by
      an interdisciplinary team) of recently diagnosed female cancer patients between
      18 and 40 years. RESULTS: Nearly all participants who applied the DA considered
      it helpful for decision-making and recommendable. Knowledge about FP was high
      with regard to FP techniques women went for. DC was moderate according to the
      mean score (M = 27.92, standard deviation = 13.27) and only in 20%, the score was
      above the threshold for high DC. There was no difference between the control and
      intervention group for knowledge and DC. CONCLUSION: The DA seems to serve as
      additional and well-accepted support tool in decision-making for patients and
      professionals. Referral to a reproductive specialist is crucial to warrant
      comprehensive information. These results need to be confirmed with the current
      ongoing randomized controlled study.

PMID- 28759304
TI  - Systemic Inflammation after Third Molar Removal: A Case-Control Study.
AB  - Third molar extraction is one of the most frequent interventions in dentistry.
      Nevertheless, there is scarce evidence on the host response of individuals with
      impacted or semi-impacted third molars and the possible effects of surgical
      removal. A case-control study of 40 patients was designed to evaluate 1) the
      differences in biomarkers of systemic inflammation, vascular function, and
      metabolism (high-sensitive C-reactive protein, lipids, fibrinogen, oxidative
      stress, and endothelial function analysis) and 2) the acute and short-term
      effects of surgical removal in patients with bilateral impacted or semi-impacted
      third molars compared to controls with no third molars. Patients undergoing third
      molar extraction exhibited greater levels of systemic inflammation, oxidative
      stress, and triglycerides than controls. Raised white blood cell counts as well
      as peaks of serum levels of C-reactive protein and fibrinogen were noticed in the
      first postoperative week. Three months after the extraction, all markers returned
      to baseline values. Malondialdehyde, an indicator of oxidative stress indicator,
      was significantly reduced after third molar removal. Semi-impacted or impacted
      third molars are associated with higher systemic inflammation, and their removal
      may represent a useful human model to study acute inflammation and determine
      beneficial systemic effects ( ClinicalTrials.gov NCT03048175).

PMID- 28759305
TI  - Accepting and Growing from "Bad Therapy" as a Young Clinician.

PMID- 28759306
TI  - Skeletal muscle regeneration involves macrophage-myoblast bonding.
AB  - Regeneration in adult skeletal muscle relies on the activation, proliferation,
      and fusion of myogenic precursor cells (MPC), mostly resident satellite cells
      (SC). However, the regulatory mechanism during this process is still under
      evaluation, with the final aim to manipulate regeneration when the intrinsic
      mechanism is corrupted. Furthermore, intercellular connections during skeletal
      muscle regeneration have not been previously thoroughly documented. Our
      hypothesis was that a direct and close cellular interaction between SC/MPC and
      invading myeloid cells is a key step to control regeneration. We tested this
      hypothesis during different steps of skeletal muscle regeneration: (a) the
      recruitment of activated SC; (b) the differentiation of MPC; (c) myotubes growth,
      in a mouse model of crush injury. Samples harvested (3 and 5 days) post-injury
      were screened by light and confocal microscopy. Ultrastructural analysis was
      performed by conventional transmission electron microscopy (TEM) and scanning
      transmission electron microscopy (STEM) followed by 3D modeling of electron
      tomography (ET) data. This revealed a new type of interaction between macrophages
      and myogenic cells by direct heterocellular surface apposition over large areas
      and long linear distances. In the analyzed volume, regions spaced below 20 nm,
      within molecular range, represented 31% of the macrophage membrane surface and
      more than 27% of the myotube membrane. The constant interaction throughout all
      stages of myogenesis suggests a potential new type of regulatory mechanism for
      the myogenic process. Thus, deciphering structural and molecular mechanisms of SC
      macrophage interaction following injury might open promising perspectives for
      improving muscle healing.

PMID- 28759307
TI  - Evaluation of Stiffness in Postmastectomy Lymphedema Using Acoustic Radiation
      Force Impulse Imaging: A Prospective Randomized Controlled Study for Identifying
      the Optimal Pneumatic Compression Pressure to Reduce Stiffness.
AB  - PURPOSE: We aimed to assess the improvement in stiffness in patients with
      postmastectomy lymphedema (PMLE) after intermittent pneumatic compression (IPC)
      using acoustic radiation force impulse (ARFI) imaging and evaluate the effects of
      different IPC pressures. METHODS: We randomly assigned 45 patients with PMLE
      (stage II) to three groups based on the IPC pressure: 25, 35, and 45 mmHg.
      Patients received a single session of IPC for 30 minutes. We recorded the
      subcutaneous tissue thickness of the proximal upper limbs using ultrasonography
      and circumference of the upper limbs and stiffness using ARFI before and
      immediately after IPC. RESULTS: Arm circumference and subcutaneous tissue
      thickness were significantly decreased after IPC in all groups. The shear wave
      velocity (SWV) decreased after IPC in all groups, but significantly decreased
      only in the 35 mmHg group. The subcutaneous tissue thickness and SWV in the 35
      mmHg group were significantly decreased compared to the other groups. CONCLUSION:
      IPC can reduce stiffness and subcutaneous tissue thickness of the proximal upper
      arm in patients with PMLE. A pressure of 35 mmHg yields the largest improvement
      of stiffness; higher compression pressure did not yield any additional
      improvement.

PMID- 28759309
TI  - Children's Accommodation to a Variety of Targets - A Pilot Study.
AB  - BACKGROUND: Previous research indicates that a significant proportion of children
      underaccommodate at 1/3 m. Accommodation may vary with task demand, so children
      may accommodate appropriately if required, for example, when reading small print.
      This study explores the range of accommodative responses elicited in typical
      children, under naturalistic conditions, to a range of targets. METHOD: We
      identified 24 typically developing children from the University of Reading Child
      Database. Primary-school children attending UK Year 2 (age 6-7 years) or Year 6
      (age 10-11 years) with minimum distance visual acuity of 0.200 logMAR and near
      visual acuity of 0.100 logMAR were recruited for participation. A remote
      haploscopic photorefractor was used to assess naturalistic, sustained, binocular
      accommodative responses to a variety of targets. At 33 cm, accommodative targets
      included individual letters, age-appropriate text in large print equivalent to
      early primary-school books, small N5 equivalent print, a visual search task
      ("Where's Wally?"), a clown picture containing a range of spatial frequencies,
      and a children's cartoon. Participants were given minimal instructions for task
      completion. The target presentation order was counterbalanced. The results
      reported in this study were obtained during a longer testing session involving
      different target types and fixation distances. RESULTS: The accommodative
      response observed with each target varied across participants to both the clown
      target and single letters of a size used in school reading books the
      accommodative responses were 2.4+/-0.48 D (range 0.85-2.97 D) and 2.47+/-0.37 D
      (range 1.48-3.09 D), respectively. The accommodative response to N5 print (3.06+/
      0.52 D) was statistically better than all other targets other than the visual
      search and larger print tasks (P<0.05). CONCLUSIONS: Even to demanding N5 text,
      accommodation is variable between participants, but is better than that to less
      demanding targets. Tasks experienced by children in everyday or clinical
      situations will stimulate an unknown amount of accommodation for near fixation.

PMID- 28759308
TI  - Vasopressin deletion is associated with sex-specific shifts in the gut
      microbiome.
AB  - Brattleboro rats harbor a spontaneous deletion of the arginine-vasopressin (Avp)
      gene. In addition to diabetes insipidus, these rats exhibit low levels of anxiety
      and depressive behaviors. Recent work on the gut-brain axis has revealed that gut
      microbiota can influence anxiety behaviors. Therefore, we studied the effects of
      Avp gene deletion on gut microbiota. Since Avp gene expression is sexually
      different, we also examined how Avp deletion affects sex differences in gut
      microbiota. Males and females show modest but differentiated shifts in taxa
      abundance across 3 separate Avp deletion genotypes: wildtype (WT), heterozygous
      (Het) and AVP-deficient Brattleboro (KO) rats. For each sex, we found examples of
      taxa that have been shown to modulate anxiety behavior, in a manner that
      correlates with anxiety behavior observed in homozygous knockout Brattleboro
      rats. One prominent example is Lactobacillus, which has been reported to be
      anxiolytic: Lactobacillus was found to increase in abundance in inverse
      proportion to increasing gene dosage (most abundant in KO rats). This genotype
      effect of Lactobacillus abundance was not found when females were analyzed
      independently. Therefore, Avp deletion appears to affect microbiota composition
      in a sexually differentiated manner.

PMID- 28759310
TI  - Ultrastructure and pathology of prion protein amyloid accumulation and cellular
      damage in extraneural tissues of scrapie-infected transgenic mice expressing
      anchorless prion protein.
AB  - In most human and animal prion diseases the abnormal disease-associated prion
      protein (PrPSc) is deposited as non-amyloid aggregates in CNS, spleen and
      lymphoid organs. In contrast, in humans and transgenic mice with PrP mutations
      which cause expression of PrP lacking a glycosylphosphatidylinositol (GPI)
      anchor, most PrPSc is in the amyloid form. In transgenic mice expressing only
      anchorless PrP (tg anchorless), PrPSc is deposited not only in CNS and lymphoid
      tissues, but also in extraneural tissues including heart, brown fat, white fat,
      and colon. In the present paper, we report ultrastructural studies of amyloid
      PrPSc deposition in extraneural tissues of scrapie-infected tg anchorless mice.
      Amyloid PrPSc fibrils identified by immunogold-labeling were visible at high
      magnification in interstitial regions and around blood vessels of heart, brown
      fat, white fat, colon, and lymphoid tissues. PrPSc amyloid was located on and
      outside the plasma membranes of adipocytes in brown fat and cardiomyocytes, and
      appeared to invaginate and disrupt the plasma membranes of these cell types,
      suggesting cellular damage. In contrast, no cellular damage was apparent near
      PrPSc associated with macrophages in lymphoid tissues and colon, with enteric
      neuronal ganglion cells in colon or with adipocytes in white fat. PrPSc localized
      in macrophage phagolysosomes lacked discernable fibrils and might be undergoing
      degradation. Furthermore, in contrast to wild-type mice expressing GPI-anchored
      PrP, in lymphoid tissues of tg anchorless mice, PrPSc was not associated with
      follicular dendritic cells (FDC), and FDC did not display typical prion
      associated pathogenic changes.

PMID- 28759311
TI  - Biglycan and Decorin Expression and Distribution in Palatal Adhesion.
AB  - Previous studies demonstrated that chondroitin sulfate proteoglycans (CSPGs) on
      apical surfaces of palatal medial edge epithelial (MEE) cells were necessary for
      palatal adhesion. In this study, we identified 2 proteoglycans, biglycan and
      decorin, that were expressed in the palatal shelves prior to adhesion. In
      addition, we established that these proteoglycans were dependent on transforming
      growth factor beta (TGFbeta) signaling. Laser capture microdissection was used to
      collect selected palatal epithelial cells from embryonic mouse embryos at various
      palate development stages. The expression of specific messenger RNA (mRNA) for
      biglycan and decorin was determined with quantitative real-time polymerase chain
      reaction. The TGFbetarI kinase inhibitor (SB431542) was used in palatal organ
      cultures to determine if blocking TFGbeta signaling changed biglycan and decorin
      distribution. Immunohistochemistry of both biglycan and decorin revealed
      expression on the apical and lateral surfaces of MEE cells. Biglycan protein and
      mRNA levels peaked as the palatal shelves adhered. Decorin was less abundant on
      the apical epithelial surface and also had reduced mRNA levels compared to
      biglycan. Their proteins were not expressed on MEE cells of palates treated with
      SB431542, an inhibitor of TGFbeta signaling. The temporal expression of biglycan
      and decorin on the apical surface of MEE, combined with the evidence that these
      proteins were regulated through the TGFbeta pathway, indicated that they may be
      important for adhesion.

PMID- 28759312
TI  - Wanted and Unwanted Care: The Double-Edged Sword of Partial Do-Not-Resuscitate
      Orders.
AB  - BACKGROUND: The interpretation of do-not-resuscitate orders (DNRs) may vary in
      nonarrest situations. To reduce ambiguity, many hospitals allow patients to elect
      partial DNRs. OBJECTIVE: To investigate the effect of partial DNRs on physicians'
      willingness to perform cardiopulmonary resuscitation (CPR) and nonarrest
      procedures. DESIGN: Cross-sectional study using scenario-based questionnaires
      between October 2015 and March 2016. A partial DNR was identified as a DNR with
      Adult Emergency Protocols (AEP) order. Each survey presented 3 patient scenarios
      followed by 10 interventions. SETTING/SUBJECTS: Preclerkship and clerkship
      medical students, and internal medicine residents at a single medical school, and
      hospitalists at a tertiary-care academic medical center. RESULTS: Responses from
      275 of 366 (75.1%) eligible subjects were collected. Compared to the case with a
      full DNR, the presence of a partial DNR was positively associated with subjects'
      willingness to provide both nonarrest procedures and CPR (p < 0.05). The number
      of training or practice years was positively associated with a decision not to
      perform CPR: case 1 (odds ratio [OR], 1.09; confidence interval [CI], 1.04-1.16;
      p = 0.003); case 2 (OR, 1.07; CI, 1.01-1.14; p = 0.03); and case 3 (OR, 1.09; CI,
      1.04-1.16; p < 0.001). CONCLUSIONS: A partial DNR made our respondents more
      willing to provide nonarrest procedures, but also CPR. These findings suggest an
      ongoing need to develop better means of incorporating patients' goals of care
      into orders that more faithfully guide care for both nonarrest and arrest
      situations.

PMID- 28759313
TI  - Glycosylation of DMP1 Is Essential for Chondrogenesis of Condylar Cartilage.
AB  - The mandibular condylar cartilage (MCC) shoulders force for the subchondral bone
      during mastication. The cartilage matrix contains various large molecules, such
      as type I, II, and X collagens and proteoglycans (PGs), which jointly play
      essential roles in maintaining cartilage characteristics. PGs play key roles in
      maintaining the elasticity of cartilage and providing a cushion against
      mastication forces. In addition to the well-known PGs, DMP1-PG, which is the PG
      form of dentin matrix protein 1 (DMP1), is a newly identified PG. DMP1 is
      proteolytically processed in vivo, and the N-terminus is glycosylated into its PG
      form-that is, DMP1-PG, which is highly expressed not only in tooth and bone but
      also in the matrix of the MCC. However, the specific functions of DMP1-PG in the
      MCC remain unclear. In human temporomandibular joint osteoarthritis and
      hyperocclusion model rat specimens, PGs are significantly downregulated, and DMP1
      PG is the most prominently affected PG. To further investigate the role of DMP1
      PG in condylar chondrogenesis, a glycosylation site mutant (S89-G89) mouse model
      was established with knock-in methods. In the MCC of the S89G-DMP1 mice, the
      glycosylation level of DMP1 was significantly downregulated, and a series of
      abnormal developmental and pathologic changes could be observed. The morphologic
      changes included thinner cartilage layers, deformations of the MCC, and
      disordered arrangements of the chondrocytes, and an earlier onset of
      temporomandibular joint osteoarthritis-like changes was observed. In addition,
      markers of chondrogenesis were downregulated, and the matrix of the MCC displayed
      OA phenotypes in the S89G-DMP1 mice. Further investigations showed that the
      transforming growth factor beta signaling molecules were affected in the MCC
      after the loss of DMP1-PG. In addition, the loss of DMP1-PG significantly
      accelerated the progression of cartilage injuries in the hyperocclusion models.
      Given these findings, we investigated the significant role of DMP1-PG in the
      chondrogenesis and maintenance of MCC.

PMID- 28759314
TI  - Enhanced Recovery After Surgery Implementation: From Planning to Success.
AB  - Enhanced Recovery After Surgery (ERAS(r)) is an evidence-based approach in
      perioperative care. The implementation and translation of ERAS pathways into
      clinical practice requires a certain investment in time and money. A
      multidisciplinary team must be gathered and should undergo training according to
      the ERAS Implementation Program. Close attention to financial aspects of
      implementation, including projecting return on investment, is necessary in
      today's cost-conscious healthcare environment. Despite frequently encountered
      barriers and resistance to change, the common objective of reducing complications
      should overcome these barriers, so that every patient benefits from the most
      appropriate perioperative care.

PMID- 28759315
TI  - Tonometry of Deep Tissues for Setting Effective Compression Pressures in
      Lymphedema of Limbs.
AB  - BACKGROUND: The therapeutic intermittent pneumatic compression (IPC) pressures
      are usually set arbitrarily at levels between 40 and 60 mmHg. However, it is not
      known how much force has been transferred to edema fluid. There is a need to know
      how high edema fluid pressures should be generated to evacuate the stagnant
      fluid. The externally applied compression force dissipates in hard tissues and
      only a portion of it is conveyed to tissue fluid. Simultaneous measuring of
      compression force using deep tissue tonometry and recording edema fluid pressures
      under a tonometer would give hints of how high should therapist or patient set
      IPC pressures to mobilize fluid. AIM: (1) To simultaneously measure the applied
      tonometer force and the generated edema fluid pressures under the tonometer, (2)
      to plot tonometer force against fluid pressure data to create a correlation curve
      for setting pressure of IPC at levels initiating fluid flow, (3) to work out a
      formula for setting pressures in the pneumatic device for individual patient,
      based on tonometry, (4) to prove the value of formula on a cohort of patients
      treated with IPC. METHODS: Deep tissue tonometry force and tissue fluid pressures
      under the tonometer indentor were measured in lower limbs in a group of 20
      patients with lymphedema stages I-III. RESULTS: (1) Deep tissue tonometry
      penetrating to a depth of 10 mm provided data on pressure generated in tissue
      fluid under the tonometer indentor. (2) Plotting the applied tonometer force
      against the tonometer-generated tissue fluid pressures revealed that force to
      reach the threshold of 30 mmHg fluid pressure necessary for initiation of flow
      should be >1000 g/sq. cm. (3) A formula, based on tonometry values, for setting
      ICP pressures at levels generating pressures for initiating edema fluid flow was
      worked out. (4) Usefulness of the formula for setting IPC at effective levels was
      proved on a cohort of patients. CONCLUSIONS: Deep tissue tonometry of limbs is
      useful for setting IPC devices at compression pressures for mobilizing edema
      fluid.

PMID- 28759316
TI  - Conservative Management for Stable High Ankle Injuries in Professional Football
      Players.
AB  - CONTEXT: High ankle "syndesmosis" injuries are common in American football
      players relative to the general population. At the professional level,
      syndesmotic sprains represent a challenging and unique injury lacking a
      standardized rehabilitation protocol during conservative management. EVIDENCE
      ACQUISITION: PubMed, Biosis Preview, SPORTDiscus, PEDro, and EMBASE databases
      were searched using the terms syndesmotic injuries, American football,
      conservative management, and rehabilitation. STUDY DESIGN: Clinical review. LEVEL
      OF EVIDENCE: Level 3. RESULTS: When compared with lateral ankle sprains,
      syndesmosis injuries result in significantly prolonged recovery times and games
      lost. For stable syndesmotic injuries, conservative management features a brief
      period of immobilization and protected weightbearing followed by progressive
      strengthening exercises and running, and athletes can expect to return to
      competition in 2 to 6 weeks. Further research investigating the efficacy of dry
      needling and blood flow restriction therapy is necessary to evaluate the benefit
      of these techniques in the rehabilitation process. CONCLUSION: Successful
      conservative management of stable syndesmotic injuries in professional American
      football athletes requires a thorough understanding of the anatomy, injury
      mechanisms, diagnosis, and rehabilitation strategies utilized in elite athletes.

PMID- 28759317
TI  - Persuasive Effects of Point of View, Protagonist Competence, and Similarity in a
      Health Narrative About Type 2 Diabetes.
AB  - We examined the persuasive effects of three narrative features in a message about
      type 2 diabetes: narrative point of view (first- vs. third-person perspective),
      protagonist competence (positive role model who prevents diabetes vs. negative
      role model who develops diabetes), and protagonist-reader similarity
      (demographically similar vs. dissimilar). We posited that a first-person point of
      view would elevate people's identification levels more than a third-person point
      of view, especially when the protagonist was depicted as a positive role model.
      We also expected a similar protagonist to foster greater levels of identification
      than a dissimilar one. In addition, the positive effect of a competent role model
      on identification was expected to be enhanced under the condition of reader
      protagonist similarity. Finally, we hypothesized that the effects of
      identification on persuasion would be mediated by self-referencing. Participants
      30 years of age or younger (N = 489) were randomly assigned to read a story about
      a person with a family history of type 2 diabetes that was altered with regard to
      the experimental factors. Thereafter they completed a questionnaire incorporating
      measures of study variables. Greater levels of identification were found to
      foster self-referencing, leading to persuasion. Identification was strongest with
      a first-person point of view and when the narrator was a positive role model. The
      effect of identification on persuasion was mediated by self-referencing. Contrary
      to expectations, protagonist-reader demographic similarity did not affect
      identification or self-referencing. There was no support for the two moderation
      hypotheses.

PMID- 28759318
TI  - The Public Health Burden of Lymphatic Malformations in Children: National
      Estimates in the United States, 2000-2009.
AB  - OBJECTIVE: Describe inpatient resource utilization trends in children with
      lymphatic malformations using a national database. DATA SOURCE: Kids' inpatient
      database, years 2000-2009. METHODS: Subjects included children 18 years and under
      with International Classification of Diseases (ICD), 9th revision code: 228.1
      lymphangioma, any site. Data elements were extracted and used to calculate
      related inpatient costs and trended over time. RESULTS: No significant increase
      in admission rates was noted over time, p = 0.5128. Average total charges per
      admission were $30,995. There is a clear and increasing trend of total charges
      per admission; even when adjusted for inflation, this has increased
      disproportionately. In 2009, the mortality rate increased to 2.58%, which was
      significantly higher than in previous years, p = 0.0346. In multivariate analysis
      for mortality, the only factor that was noted to be significant was between
      survey years 2000 and 2009. The odds ratio (OR) for mortality was 2.97, 95% CI:
      [1.423-6.202], which indicated that there was an almost three times higher
      likelihood of mortality in 2009 than in 2000. CONCLUSIONS: Admission rates appear
      to remain stable for pediatric inpatients with lymphatic malformations but
      resource utilization related to charges has been increasing from 2000 to 2009.
      Controlling for inflation does not explain our observed trend in total charge
      increases. Previously, surgical resection was the most commonly performed
      procedure, and now the trend has shifted away from operative intervention.
      Mortality rates, while low, experienced a rise in 2009. Further investigation may
      be warranted.

PMID- 28759319
TI  - An Experimental Lymphedema Animal Model for Assessing the Results of Lymphovenous
      Anastomosis.
AB  - BACKGROUND: The lymphatic system is the least studied of the body's systems, and
      as a result its contribution to human health and diseases is not well known. The
      failure of the lymphatic system to drain extravasated fluid efficiently leads to
      accumulation of lymph in the interstitial tissue, thus causing lymphedema.
      Despite developments in microsurgery procedures, the results of lymphedema
      treatment remain disappointing. The aim of this study was to develop an
      experimental animal model that is able to reproduce the disease and to apply
      various surgical and therapeutic approaches. METHODS AND RESULTS: Lymphedema was
      induced in New Zealand white rabbits by a total skin denudation and destruction
      of the lymph channels via microsurgery in the right ear, leaving the left ear as
      control. Lymphedema generation was observed between days 7 and 15 after
      intervention. On day 15, a terminal venous lymphatic anastomosis was performed on
      the posterior edge of the right ear. Serial measurements of ear thickness were
      made during the study. Ear thickness was significantly (p < 0.05) increased after
      lymphedema induction compared to baseline (3.2 +/- 0.4 vs. 1.3 +/- 0.04 mm).
      After anastomosis, ear thickness was reduced (2 +/- 0.26 mm). CONCLUSION: This
      animal model of lymphedema induction in the ear proved to be a reproducible
      alternative for studying new approaches to lymphedema treatment and for
      developing microsurgical skills.

PMID- 28759320
TI  - A Cross-Comparative Survey of Information Seeking and Scanning About Drug-Related
      Sources and Topics Among U.S. and Israeli College Students.
AB  - There is an increasing amount of drug-related information that is easily
      accessible from media and interpersonal sources. Recent research shows
      significant positive associations between information acquisition and nonmedical
      drug use intentions among college students. This study examines information about
      amphetamines and marijuana that was actively searched ("seeking") as well as
      information that was encountered during routine media use ("scanning"). Data are
      drawn from a cross-national comparative survey of college students in the United
      States (N = 734) and in Israel (N = 800). U.S. participants reported seeking and
      scanning information about marijuana across a broader range of sources than
      Israeli participants. Among U.S. and Israeli participants, the most frequently
      searched marijuana-related topics included the benefits of marijuana, negative
      effects of marijuana use, and political reasons why marijuana should be legal.
      Participants from both countries reported the benefits of amphetamines, and the
      negative effects of amphetamine use as the most frequently searched topics about
      amphetamines. Participants in both countries identified the internet and friends
      as the most popular sources of drug-related information and noted that
      physicians, friends, and the internet were the most trusted sources. Implications
      for research on information seeking and health communication are discussed.

PMID- 28759321
TI  - First Report on a Randomized Investigation of Antimicrobial Resistance in Fecal
      Indicator Bacteria from Livestock, Poultry, and Humans in Tanzania.
AB  - This study provides an estimate of antimicrobial resistance in intestinal
      indicator bacteria from humans (n = 97) and food animals (n = 388) in Tanzania.
      More than 70% of all fecal samples contained tetracycline (TE), sulfamethoxazole
      (STX), and ampicillin (AMP)-resistant coliforms, while cefotaxime (CTX)-resistant
      coliforms were observed in 40% of all samples. The average Log10 colony forming
      units/g of CTX-resistant coliforms in samples from humans were 2.20. Of 390
      Escherichia coli tested, 66.4% were resistant to TE, 54.9% to STX, 54.9% to
      streptomycin, and 36.4% to CTX. Isolates were commonly (65.1%) multiresistant.
      All CTX-resistant isolates contained blaCTX-M gene type. AMP- and vancomycin
      resistant enterococci were rare, and the average concentrations in positive
      samples were low (log10 0.9 and 0.4, respectively). A low-to-moderate resistance
      (2.1-15%) was detected in 240 enterococci isolates to the drugs tested, except
      for rifampicin resistance (75.2% of isolates). The average number of sulII gene
      copies varied between Log10 5.37 and 5.68 with no significant difference between
      sample source, while cattle had significantly higher number of tetW genes than
      humans. These findings, based on randomly obtained samples, will be instrumental
      in designing antimicrobial resistance (AMR) intervention strategies for Tanzania.

PMID- 28759322
TI  - Diversity and dynamics of the DNA- and cDNA-derived compost fungal communities
      throughout the commercial cultivation process for Agaricus bisporus.
AB  - Commercial cultivation of the button mushroom Agaricus bisporus is performed
      through the inoculation of a semipasteurized composted material. Pasteurization
      of the compost material prior to inoculation results in a substrate with a fungal
      community that becomes dominated by A. bisporus. However, little is known about
      the composition and activity in the wider fungal community beyond the presence of
      A. bisporus in compost throughout the mushroom cropping process. In this study,
      the fungal cropping compost community was characterized by sequencing nuc rDNA
      ITS1-5.8S-ITS2 amplified from extractable DNA and RNA. The fungal community
      generated from DNA extracts identified a diverse community containing 211 unique
      species, although only 51 were identified from cDNA. Agaricus bisporus was found
      to dominate in the DNA-derived fungal community for the duration of the cropping
      process. However, analysis of cDNA extracts found A. bisporus to dominate only up
      to the first crop flush, after which activity decreased sharply and a much
      broader fungal community became active. This study has highlighted the diverse
      fungal community that is present in mushroom compost during cropping.

PMID- 28759323
TI  - Designing Home-Based Telemedicine Systems for the Geriatric Population: An
      Empirical Study.
AB  - : Background and Introduction: Telemedicine, the process of providing healthcare
      remotely using communication devices, has the potential to be useful for the
      geriatric population when specifically designed for this age group. This study
      explored the design of four video telemedicine systems currently available and
      outlined issues with these systems that impact usability among the geriatric
      population. Based on the results, design suggestions were developed to improve
      telemedicine systems for this population. MATERIALS AND METHODS: Using a between
      subjects experimental design, the study considered four telemedicine systems used
      in Medical University of South Carolina. The study was conducted at a local
      retirement home. The participant pool consisted of 40 adults, 60 years or older.
      The dependent measures used were the mean times for telemedicine session
      initiation and video session, mean number of errors, post-test satisfaction
      ratings, the NASA-Task Load Index (NASA-TLX) workload measures, and the IBM
      Computer Systems Usability Questionnaire measures. RESULTS: Statistical
      significance was found among the telemedicine systems' initiation times. The
      analysis of the qualitative data revealed several issues, including lengthy e
      mail content, icon placement, and chat box design, which affect the usability of
      these systems for the geriatric population. DISCUSSION: Human factor-based design
      modifications, including short, precise e-mail content, appropriately placed
      icons, and the inclusion of instructions, are recommended to address the issues
      found in the qualitative study.

PMID- 28759324
TI  - Non-Suicidal Self-Injury, Sexuality Concerns, and Emotion Regulation among
      Sexually Diverse Adolescents: A Multiple Mediation Analysis.
AB  - Despite increasing interest in the prevalence and correlates of Non-Suicidal Self
      Injury (NSSI) in adolescent populations, relatively few studies have examined
      NSSI among lesbian, gay and bisexual (LGB) adolescents. The current study
      explored sexuality concerns and elevated emotion dysregulation as potential
      mechanisms underlying the relationship between sexual orientation and elevated
      non-suicidal self-injury (NSSI). A community sample of 1,799 adolescents
      completed a questionnaire assessing NSSI, sexual orientation, sexuality concerns,
      and emotion regulation. Across the study, 20.6% of adolescents reported a history
      of NSSI. Adolescents who identify as "mostly heterosexual," "bisexual," and
      "mostly homosexual" were more likely to engage in NSSI than gay/lesbian,
      heterosexual, and asexual adolescents. Multiple mediation analysis showed that
      emotion regulation, but not sexuality concerns, mediated the relationship between
      sexual orientation and NSSI. The current study tested two theoretical pathways by
      which sexual orientation could predict NSSI engagement. Findings suggest that
      literature on general psychological processes, as well as group-specific minority
      stressors, can shed light on high rates of NSSI among LGB populations.
      Specifically, the challenges faced by LGB adolescents may undermine the
      development of emotion regulation. As such, this should be a key target of
      intervention with LGB adolescents engaging in NSSI.

PMID- 28759325
TI  - Corrigendum: The Social Reach: 8-Month-Olds Reach for Unobtainable Objects in the
      Presence of Another Person.
AB  - Original article: Ramenzoni, V. C., & Liszkowski, U. (2016). The social reach: 8
      month-olds reach for unobtainable objects in the presence of another person.
      Psychological Science, 27, 1278-1285. doi:10.1177/0956797616659938.

PMID- 28759326
TI  - Assessment of Strangulation in Adhesive Small Bowel Obstruction on the Basis of
      Combined CT Findings: Implications for Clinical Care.
AB  - Purpose To determine which computed tomography (CT) findings or combinations of
      findings can help to accurately identify strangulation in adhesive small bowel
      obstruction (SBO). Materials and Methods Contrast agent-enhanced CT findings in a
      cohort of 256 patients consecutively admitted for adhesive SBO, with a delay of
      less than 24 hours between CT and surgery for the operated patients, were
      reviewed independently by two radiologists, with consensus by a third, to assess
      CT findings commonly associated with strangulation. The reference standard for
      strangulation was surgery. Univariate and multivariate analyses were performed to
      identify predictors of strangulation in the entire cohort and to identify
      predictors of the need for surgical resection in the subgroup of patients with
      strangulation. A CT score was obtained and diagnostic performances of different
      combined CT findings were calculated. Results In this study, 105 patients (41.0%;
      105 of 256) underwent a surgical procedure, 62 of whom were found to have
      strangulation (59.0%; 62 of 105), whereas 151 patients (59.0%; 151 of 256)
      improved with medical care. Three CT findings were significantly associated with
      strangulation in the multivariate analysis: reduced bowel wall enhancement (odds
      ratio, 7.8; 95% confidence interval [CI]: 2.6, 23.5), diffuse mesenteric haziness
      (odds ratio, 6.1; 95% CI: 2.5, 15.2), and a closed-loop mechanism (odds ratio,
      6.5; 95% CI: 2.8, 15.5). The model combining these three features had an area
      under the curve of 0.91 (95% CI: 0.86, 0.96) and a high negative predictive value
      (97%; 95% CI: 93%, 99%). Positive likelihood ratios were high when two or three
      of these CT findings were combined (positive likelihood ratios, 14.7 [95% CI:
      7.1, 30.4] and 43.8 (95% CI: 14.2, 135.2], respectively). Among the strangulated
      cases, reduced bowel wall enhancement (odds ratio, 3.9; 95% CI: 1.3, 12) and
      mesenteric fluid (odds ratio, 3.6; 95% CI: 1.0, 12.8) were predictive of
      resection. Conclusion A score that combines three CT findings (reduced bowel wall
      enhancement, a closed-loop mechanism, and diffuse mesenteric haziness) can
      accurately predict strangulation in adhesive SBO. (c) RSNA, 2017 Online
      supplemental material is available for this article.

PMID- 28759327
TI  - Factors of Pelvic Infection and Death in Patients with Open Pelvic Fractures and
      Rectal Injuries.
AB  - BACKGROUND: Open pelvic fractures associated with rectal injuries are uncommon.
      They often cause serious pelvic infection, even death. This combination of
      injuries has been reviewed infrequently. Herein, we report factors associated
      with pelvic infection and death in a group of patients with open pelvic fractures
      and concurrent rectal injuries. METHODS: We retrospectively reviewed the records
      of patients with open pelvic fractures and rectal injuries who were treated at
      our institution from January 2010-April 2014. From the medical records, age,
      gender, Injury Severity Score (ISS), cause of fracture, associated injuries,
      classification of the fracture, degree of soft-tissue injury, Glasgow Coma Score
      (GCS), Revised Trauma Score (RTS), packed red blood cells (PRBCs) needed,
      presence/absence of shock, early colostomy (yes or no), drainage (yes or no), and
      rectal washout (yes or no) were extracted. Univariable and multivariable analysis
      were performed to determine the association between risk factors and pelvic
      infection or death. RESULTS: Twenty patients were identified. Pelvic infection
      occurred in 50% (n = 10) of the patients. Four patients suffered septicemia, and
      three patients died of multiple organ dysfunction. The mortality rate thus was
      15%. According to the univariable analysis, the patients in whom pelvic infection
      developed had shock, RTS <=8, GCS <=8, blood transfusion >=10 units in the first
      24 h, no colostomy, or Gustilo grade III soft-tissue injury. According to the
      multivariable analysis, shock and absence of colostomy were independently
      associated with pelvic infection. By univariable analysis, the only factor
      associated with death was RTS <=8. CONCLUSION: The incidence of pelvic infection
      was lower in patients having early colostomy (p < 0.05). Patients with shock had
      a higher risk of pelvic infection, and we recommend aggressive measures to treat
      these patients. According to our results, RTS <=8 could be a predictor of poor
      outcomes in patients with open pelvic fracture and concurrent rectal injury. Open
      reduction and internal fixation after extensive debridement is recommended in
      patients with unstable pelvic fractures.

PMID- 28759328
TI  - Molecular Dynamics Simulations of Quinolone Resistance-Associated T86I and P104S
      Mutations in Campylobacter jejuni gyrA: Unraveling Structural Repercussions.
AB  - gyrA is a clinically validated therapeutic drug target that catalyzes changes in
      DNA topology by introducing negative supercoils into DNA. The broad-spectrum
      quinolones are hitherto the most potent antibacterial agents targeted toward
      gyrA. Increasing resistance to quinolones is accompanied by several mutations in
      the quinolone resistance-determining region of gyrA. In the present study, we
      report a comprehensive picture of the dynamic behavior of wild-type, T86I, and
      T86I/P104S mutants (MTs) of gyrA from Campylobacter jejuni in complex with
      ciprofloxacin to unravel the atomistic details of the mechanism underlying
      resistance to quinolones. Our simulation results reveal that no substantial
      conformational changes were observed. It was observed that these mutations
      disrupted residue interaction network landscape to a significant extent, which
      would affect ligand binding affinity. A distinctive pattern of dominant motions
      was clearly discernible in wild and MT gyrA forms. The results reported in this
      study associate gyrA mutations with quinolone resistance and would pave a way for
      facilitating wet laboratory researchers to develop gyrA MT-based therapeutic
      strategies against resistant pathogens.

PMID- 28759329
TI  - Health Literacy and Informed Consent Materials: Designed for Documentation, Not
      Comprehension of Health Research.
AB  - Minority populations with health disparities are underrepresented in research
      designed to address those disparities. One way to improve minority representation
      is to use community-based participatory methods to overcome barriers to research
      participation, beginning with the informed consent process. Relevant barriers to
      participation include lack of individual or community awareness or acceptance of
      research processes and purposes. These barriers are associated with limited
      health literacy. To inform recommendations for an improved consent process, we
      examined 97 consent documents and 10 associated Institutional Review Board
      websites to determine their health literacy demands and degree of adherence to
      principles of community-based research. We assessed the reading level of consent
      documents and obtained global measures of their health literacy demand by using
      the Suitability and Comprehensibility Assessment of Materials instrument.
      Although these documents were deemed suitable as medical forms, their readability
      levels were inappropriate, and they were unsuitable for educating potential
      participants about research purposes. We also assessed consent forms and
      Institutional Review Board policies for endorsement of community-based
      participatory principles, finding that very few acknowledged or adhered to such
      principles. To improve comprehension of consent documents, we recommend
      restructuring them as educational materials that adhere to current health
      literacy guidelines.

PMID- 28759330
TI  - Giant Viruses of Amoebae: A Journey Through Innovative Research and Paradigm
      Changes.
AB  - Giant viruses of amoebae were discovered serendipitously in 2003; they are
      visible via optical microscopy, making them bona fide microbes. Their lifestyle,
      structure, and genomes break the mold of classical viruses. Giant viruses of
      amoebae are complex microorganisms. Their genomes harbor between 444 and 2,544
      genes, including many that are unique to viruses, and encode translation
      components; their virions contain >100 proteins as well as mRNAs. Mimiviruses
      have a specific mobilome, including virophages, provirophages, and transpovirons,
      and can resist virophages through a system known as MIMIVIRE (mimivirus virophage
      resistance element). Giant viruses of amoebae bring upheaval to the definition of
      viruses and tend to separate the current virosphere into two categories: very
      simple viruses and viruses with complexity similar to that of other microbes.
      This new paradigm is propitious for enhanced detection and characterization of
      giant viruses of amoebae, and a particular focus on their role in humans is
      warranted.

PMID- 28759331
TI  - Reliability and Diagnostic Thresholds for Ultrasound Measurements of Dermal
      Thickness in Breast Lymphedema.
AB  - BACKGROUND: Lymphedema of the breast, secondary to treatment for breast cancer,
      is difficult to assess due to the shape of the breast and the nature of the
      tissue. Ultrasound measurement of dermal thickness has been previously used to
      assess breast swelling; however, the reliability of the measurements, or what
      should be considered an abnormal thickness, is currently known. METHODS AND
      RESULTS: Thirty-eight women with breast edema were recruited and underwent
      assessment using ultrasound. During the assessment, the four quadrants (superior,
      inferior, medial, and lateral) of the affected and unaffected breasts were imaged
      three times each. Dermal thickness was then measured by two assessors, on two
      occasions for each captured image. The interimage, intrarater, and inter-rater
      reliability was all found to be excellent (Cronbach's alpha = 0.995; ICC(3,1) =
      0.962 and 0.851; and ICC(2,1) = 0.977, respectively). A dermal thickness of >1.6
      mm in the superior and lateral quadrants and 2.0 mm in the medial and inferior
      quadrants was determined, by receiver-operating characteristics curve analysis,
      as the optimal diagnostic threshold to detect breast edema. CONCLUSION: Dermal
      thickness measurements can be reliably completed on breasts with edema secondary
      to breast cancer. Future study is needed to determine the utility of the dermal
      thickness thresholds established as well as to investigate changes in dermal
      thickness as a response to treatment of breast edema.

PMID- 28759332
TI  - The cellular prion protein (PrPC) as neuronal receptor for alpha-synuclein.
AB  - The term 'prion-like' is used to define some misfolded protein species that
      propagate intercellularly, triggering protein aggregation in recipient cells. For
      cell binding, both direct plasma membrane interaction and membrane receptors have
      been described for particular amyloids. In this respect, emerging evidence
      demonstrates that several beta-sheet enriched proteins can bind to the cellular
      prion protein (PrPC). Among other interactions, the physiological relevance of
      the binding between beta-amyloid and PrPC has been a relevant focus of numerous
      studies. At the molecular level, published data point to the second charged
      cluster domain of the PrPC molecule as the relevant binding domain of the beta
      amyloid/PrPC interaction. In addition to beta-amyloid, participation of PrPC in
      binding alpha-synuclein, responsible for neurodegenerative synucleopathies, has
      been reported. Although results indicate relevant participation of PrPC in the
      spreading of alpha-synuclein in living mice, the physiological relevance of the
      interaction remains elusive. In this comment, we focus our attention on
      summarizing current knowledge of PrPC as a receptor for amyloid proteins and its
      physiological significance, with particular focus on alpha-synuclein.

PMID- 28759335
TI  - Tubercular Abdominal Cocoon: Systematic Review of an Uncommon Form of
      Tuberculosis.
AB  - BACKGROUND: Abdominal cocoon formation is an uncommon manifestation of abdominal
      tuberculosis that is characterized by the formation of a fibrous membrane-like
      sac around the small intestinal loops. Appropriate treatment and outcomes are
      uncertain Objectives: To review the clinical presentation, treatment, and
      outcomes for tubercular abdominal cocoon (TAC). PATIENTS AND METHODS: We included
      studies published in the English language and listed in EMBASE or PubMed. All
      case series or reports that reported patients with TAC were considered for
      inclusion. Details regarding demographic, clinical presentation, and treatment
      received were tabulated. RESULTS: The clinical features included predominantly
      abdominal pain, abdominal distension and features of intestinal obstruction, loss
      of appetite, and weight loss. The diagnosis was usually established at surgery,
      however, computed tomography was a useful tool. In most patients the treatment
      reported was surgical, however, conservative therapy with anti-tubercular therapy
      (ATT) did succeed in a subset of patients. The published literature includes only
      case series and reports. The outcomes, especially long-term outcomes, have not
      been reported in most studies. CONCLUSION: Abdominal cocoon is an uncommon form
      of abdominal tuberculosis and conservative management with ATT may suffice in
      some patients whereas non-responsive cases require surgery.

PMID- 28759334
TI  - B Cell Tetramer Development for Veterinary Vaccinology.
AB  - Immunological memory is elicited after either vaccination or natural exposure to
      a pathogen and is essential for protection against re-exposure. Despite its
      critical importance, the ability to interrogate the veterinary animal memory
      immune response has long been hindered by a paucity of tools to assess
      immunological memory. As a result, the evaluation and analysis of protective
      immune responses that predict immune protection in food and fiber animals and
      facilitate vaccine development are obstructed. To fill this gap in knowledge in
      swine, we created a B cell tetramer to porcine reproductive and respiratory
      syndrome virus (PRRSV) nonstructural protein 7 (nsp7) to efficiently and
      effectively investigate the memory B cell response, a hallmark of anti-viral
      immunity. This novel reagent was validated by using a modified capture ELISA,
      tetramer pulldowns, and flow cytometry, and it was shown to detect rare, antigen
      specific B cells that were present at a frequency of about 0.001% of total B
      lymphocytes in immune animals. The nsp7-B cell tetramer will help to characterize
      the PRRSV-specific memory B cell response, which is fundamentally important for
      understanding immunological competence and animal variation in resistance to
      PRRSV infection. We expect that the method will be widely applicable to the
      exploration of immunity to veterinary pathogens.

PMID- 28759333
TI  - Do Pattern-Focused Visuals Improve Skin Self-Examination Performance? Explicating
      the Visual Skill Acquisition Model.
AB  - Skin self-examination (SSE) consists of routinely checking the body for atypical
      moles that might be cancerous. Identifying atypical moles is a visual task; thus,
      SSE training materials utilize pattern-focused visuals to cultivate this skill.
      Despite widespread use, researchers have yet to explicate how pattern-focused
      visuals cultivate visual skill. Using eye tracking to capture the visual
      scanpaths of a sample of laypersons (N = 92), the current study employed a 2
      (pattern: ABCDE vs. ugly duckling sign [UDS]) * 2 (presentation: photorealistic
      images vs. illustrations) factorial design to assess whether and how pattern
      focused visuals can increase layperson accuracy in identifying atypical moles.
      Overall, illustrations resulted in greater sensitivity, while photos resulted in
      greater specificity. The UDS * photorealistic condition showed greatest
      specificity. For those in the photo condition with high self-efficacy, UDS
      increased specificity directly. For those in the photo condition with self
      efficacy levels at the mean or lower, there was a conditional indirect effect
      such that these individuals spent a larger amount of their viewing time observing
      the atypical moles, and time on target was positively related to specificity.
      Illustrations provided significant gains in specificity for those with low-to
      moderate self-efficacy by increasing total fixation time on the atypical moles.
      Findings suggest that maximizing visual processing efficiency could enhance
      existing SSE training techniques.

PMID- 28759336
TI  - Patterns of Non-Suicidal Self-Injury and Their Relationship with Suicide Attempts
      in Youth with Borderline Personality Disorder.
AB  - The study aimed to identify the relationships between patterns of non-suicidal
      self-injury (NSSI), their severity, and suicide attempts among 107 youth (aged 15
      25 years) with borderline personality disorder (BPD). Two principal patterns were
      identified via a graphical representation of retrospectively reported 12-month
      histories of NSSI. These were habitual (NSSI occurring at regular intervals) and
      random patterns (NSSI inconsistently spaced). Habitual patterns of NSSI were
      associated with lower severity and fewer suicide attempts than random patterns.
      Within-person comparisons revealed a reduction in NSSI engaged within a habitual
      pattern and an increase in NSSI engaged within a random pattern in the month
      prior to a suicide attempt. Findings suggest that the accuracy of risk
      assessments among youth with BPD might be improved by identifying an individual's
      historical pattern of NSSI, as well as any relative increase in NSSI engaged
      within a random pattern or relative reduction in NSSI engaged within a habitual
      pattern.

PMID- 28759337
TI  - Detection of Coxiella burnetii DNA in Peridomestic and Wild Animals and Ticks in
      an Endemic Region (Canary Islands, Spain).
AB  - Coxiella burnetii, the etiological agent of human Q fever, can infect mammals,
      birds, and arthropods. The Canary Islands (Spain) are considered an endemic
      territory, with a high prevalence in both humans and livestock. Nonetheless,
      there is no epidemiological information about the wild and peridomestic cycles of
      C. burnetii. Tissue samples from rodents on farms (100) and wild rabbits (129)
      were collected and assessed by PCR to detect C. burnetii DNA. In parallel, ticks
      were also collected from vegetation (1169), livestock (335), domestic dogs (169),
      and wild animals (65). Globally, eight rodents (8%) and two rabbits (1.5%) were
      found to be positive, with the spleen being the most affected organ. Tick species
      identified were Hyalomma lusitanicum, Rhipicephalus turanicus, Rhipicephalus
      sanguineus, and Rhipicephalus pusillus. Hyalomma lusitanicum (80%) was the main
      species identified in vegetation, livestock, and wild animals, whereas
      Rhipicephalus sanguineus was the most prevalent in domestic dogs. Overall, C.
      burnetii DNA was detected in 6.1% of the processed ticks, distributed between
      those removed from livestock (11.3%), domestic dogs (6.9%), and from wild animals
      (6%). Ticks from vegetation were all negative. Results suggest that, in the
      Canary Islands, C. burnetii develops in a peridomestic rather than a wild cycle.

PMID- 28759339
TI  - Corrigendum: Information Search in Decisions From Experience: Do Our Patterns of
      Sampling Foreshadow Our Decisions?
AB  - Original article: Hills, T. T., & Hertwig, R. (2010). Information search in
      decisions from experience: Do our patterns of sampling foreshadow our decisions?
      Psychological Science, 21, 1787-1792. doi:10.1177/0956797610387443.

PMID- 28759338
TI  - "People" can be better than "you": The moderating role of regulatory focus on
      self-referencing messages in physical activity promotion campaigns among college
      students.
AB  - Self-referencing effects explain why many advertisements try to relate people
      with the ads; when an individual relates an ad to the self, the person will be
      more likely to recall the ad. However, this study revealed that the regulatory
      focus of messages is a boundary condition for self-referencing strategy. Self
      referencing did not yield a positive persuasion effect in prevention-focused
      messages. The underlying message process analyses further revealed people avoid
      elaborating prevention-focused messages when used with self-referencing, rather
      than viewing them in a biased manner. The findings provide guidance for health
      communication practitioners' use of self-referencing statements.

PMID- 28759340
TI  - Employers' Perspective on Childcare Services for Hired Farm Workers.
AB  - The goal of this project was to protect children while parents work in
      agriculture by improving off-farm services for children of migrant and seasonal
      farm workers. Large agricultural enterprises have policies forbidding children in
      the worksite. At the same time, their employees, who are trying to generate
      income, seek as many work hours as possible but often lack viable options for
      childcare services. As employers strive to increase their labor pool, and workers
      seek off-farm childcare, there is mutual interest in improving access to
      childcare services in agricultural regions dependent on large numbers of full
      time and seasonal workers. This report describes the employers' perspectives on
      childcare needs of hired farm workers' families and their barriers and motivators
      to facilitating off-farm childcare services. Using descriptive survey research
      methodology, data were collected from a convenience sample of 102 agribusiness
      owners and Human Resource directors attending an agricultural conference
      regarding labor laws or personnel management. Results revealed significant
      differences for those companies employing more than 25 workers compared to their
      counterparts. Primary motivators for offering childcare as an employment benefit
      were improved employee morale, enhanced company reputation, and a more stable
      workforce. A major barrier was that half of large-scale enterprises lack guidance
      on how to provide childcare options for their workers. Survey results are being
      used to facilitate collaboration among employers, farm workers, and childcare
      providers to offer a safe, nurturing environment for children while their parents
      work in agriculture.

PMID- 28759341
TI  - A Test of How Australian Adults Allocate Time for Physical Activity.
AB  - The most common reported barrier to physical activity is a lack of sufficient
      time. Just like most resources in economics are finite, so too is time within a
      day. We utilized a time-utility model to better understand how people are
      allocating time for physical activity. Additionally, we tested whether the
      allocation of physical activity time impacts people's perception of "lack of
      time" as a barrier for physical activity or their likelihood of being
      sufficiently physical active. Australian adults (N = 725 participants, 54% men)
      reported their time use throughout their day, perceived lack of time as a barrier
      to activity, and physical activity. Cluster analysis and chi2-tests were used to
      test the study research questions. People tended to either be entirely inactive
      (29%) or active while doing either leisure (18%), occupation (18%), transport
      (14%), or household (22%) activities. Those who were active during their leisure
      or transport time were most likely to be sufficiently active. There were no
      significant differences among clusters in how much people perceived that lack of
      time was a physical activity barrier. The commonly reported barrier of not having
      enough time to be active might be a fallacy. Although a lack of time is a
      commonly reported barrier of physical activity, these findings bring to light
      that increasing physical activity behavior is not as simple as adding more time
      to the day.

PMID- 28759342
TI  - Respiratory Protection Program Compliance in Iranian Hospitals: Application of
      Fuzzy Analytical Hierarchy Process.
AB  - In hospitals, health care workers (HCWs) are exposed to a wide range of
      respiratory hazards, which requires using respiratory protective equipment and
      implementing Respiratory Protection Programs (RPPs). The aim of this cross
      sectional study was to investigate RPP implementation in 36 teaching hospitals
      located in the Fars province of Iran. A researcher-developed checklist, including
      nine components of the RPP standard, was completed by industrial hygienists in
      the study hospitals. The Fuzzy Analytical Hierarchy Process (FAHP) was used to
      determine the weight coefficient of RPP components. Finally, a Respiratory
      Protection Program Index (RPPI) was developed to calculate hospital compliance
      with RPP. The results showed that RPP were not fully implemented in the studied
      hospitals, and the highest and lowest RPPI scores were related to training and
      fit testing, respectively. To promote the implementation of RPP, significant
      efforts are required for all components, especially fit testing and worker
      evaluation.

PMID- 28759343
TI  - Epidemiologic study of major complications in adolescent and adult patients with
      thalassemia in Northeastern Thailand: the E-SAAN study phase I.
AB  - INTRODUCTION: Thalassemia-related complications are one of the main factors that
      increase morbidity and mortality in aging patients with thalassemia. This study
      was aimed to report the prevalence and clinical risk factors for the
      complications in thalassemia. METHODS: A multi-center prospective cohort study
      was conducted in patients with thalassemia aged >=10 years old. Thalassemia
      related complications were heart failure, pulmonary hypertension, extramedullary
      hematopoiesis, endocrine disorders, infections, thrombosis and leg ulcers. The
      clinical parameters significantly associated with the complications were analyzed
      by logistic regression methods. RESULTS: The prevalence of thalassemia-related
      complications was 60.5% in patients with transfusion-dependent thalassemia (TDT)
      and 43% in patients with non-transfusion-dependent thalassemia (NTDT).
      Splenectomy was statistically associated with complications in both TDT and NTDT
      patients (adjusted odds ratio (AOR) = 7.4, p-value = 0.0001 and AOR = 2.6, p
      value = 0.001). Age >=50 years old (AOR = 2.9, p-value = 0.04) and female gender
      (AOR = 0.5, p-value = 0.03) were statistically associated with the complications
      in patients with NTDT. CONCLUSION: Nearly half of the patients in this cohort had
      disease-related complications. Splenectomy and advanced age were important
      factors for complication involvement. Early screening for the complications may
      reduce the morbidity and mortality in patients with thalassemia.

PMID- 28759344
TI  - Women's autonomy and reproductive health-care-seeking behavior in Ethiopia.
AB  - This paper investigated the potential importance of women's autonomy in
      reproductive health-care-seeking behavior of women in Ethiopia. Data from the
      2011 Ethiopian Demographic and Health survey (DHS), which involved a total of
      16,515 women, were analyzed. A weighted sub-sample of married women and women who
      had a live birth were included in analyses on family planning and antenatal care.
      Women's autonomy was measured by participation in decision making, attitudes
      toward wife beating, and whether getting permission to seek medical care was a
      big problem. Nearly 54% of women participated in all major household decisions,
      and 69% said getting permission to go for medical care was not a large problem.
      Women's participation in domestic decision making was significantly positively
      associated with use of family planning (adjusted odds ratio [aOR]: 1.37, 95%
      confidence interval [CI]: 1.17-1.62), and antenatal care (aOR: 1.36, 95% CI: 1.13
      1.64) after adjusting for the effects of socio-demographic variables. Moreover,
      greater women's education, paid employment, exposure to media, and better
      household economic status were related to both use of family planning and
      antenatal care. Improving women's autonomy will help to attain both gender
      equality and improved use of health services.

PMID- 28759346
TI  - Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline
      Update.
AB  - Purpose To update the ASCO guideline for antiemetics in oncology. Methods ASCO
      convened an Expert Panel and conducted a systematic review of the medical
      literature for the period of November 2009 to June 2016. Results Forty-one
      publications were included in this systematic review. A phase III randomized
      controlled trial demonstrated that adding olanzapine to antiemetic prophylaxis
      reduces the likelihood of nausea among adult patients who are treated with high
      emetic risk antineoplastic agents. Randomized controlled trials also support an
      expanded role for neurokinin 1 receptor antagonists in patients who are treated
      with chemotherapy. Recommendation Key updates include the addition of olanzapine
      to antiemetic regimens for adults who receive high-emetic-risk antineoplastic
      agents or who experience breakthrough nausea and vomiting; a recommendation to
      administer dexamethasone on day 1 only for adults who receive anthracycline and
      cyclophosphamide chemotherapy; and the addition of a neurokinin 1 receptor
      antagonist for adults who receive carboplatin area under the curve >= 4 mg/mL per
      minute or high-dose chemotherapy, and for pediatric patients who receive high
      emetic-risk antineoplastic agents. For radiation-induced nausea and vomiting,
      adjustments were made to anatomic regions, risk levels, and antiemetic
      administration schedules. Rescue therapy alone is now recommended for low-emetic
      risk radiation therapy. The Expert Panel reiterated the importance of using the
      most effective antiemetic regimens that are appropriate for antineoplastic agents
      or radiotherapy being administered. Such regimens should be used with initial
      treatment, rather than first assessing the patient's emetic response with less
      effective treatment. Additional information is available at
      www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .

PMID- 28759347
TI  - Response to Radiotherapy After Breast-Conserving Surgery in Different Breast
      Cancer Subtypes in the Swedish Breast Cancer Group 91 Radiotherapy Randomized
      Clinical Trial.
AB  - Purpose To evaluate the effect of adjuvant radiotherapy (RT) after breast
      conservation surgery in different breast cancer subtypes in a large, randomized
      clinical trial with long-term follow-up. Patients and Methods Tumor tissue was
      collected from 1,003 patients with node-negative, stage I and II breast cancer
      who were randomly assigned in the Swedish Breast Cancer Group 91 Radiotherapy
      trial between 1991 and 1997 to breast conservation surgery with or without RT.
      Systemic adjuvant treatment was sparsely used (8%). Subtyping was performed with
      immunohistochemistry and in situ hybridization on tissue microarrays for 958
      tumors. Results RT reduced the cumulative incidence of ipsilateral breast tumor
      recurrence (IBTR) as a first event within 10 years for luminal A-like tumors (19%
      v 9%; P = .001), luminal B-like tumors (24% v 8%; P < .001), and triple-negative
      tumors (21% v 6%; P = .08), but not for human epidermal growth factor receptor 2
      positive (luminal and nonluminal) tumors (15% v 19%; P = .6); however, evidence
      of an overall difference in RT effect between subtypes was weak ( P = .21). RT
      reduced the rate of death from breast cancer (BCD) for triple-negative tumors
      (hazard ratio, 0.35; P = .06), but not for other subtypes. Death from any cause
      was not improved by RT in any subtype. A hypothesized clinical low-risk group did
      not have a low risk of IBTR without RT, and RT reduced the rate of IBTR as a
      first event after 10 years (20% v 6%; P = .008), but had no effect on BCD or
      death from any cause. Conclusion Subtype was not predictive of response to RT,
      although, in our study, human epidermal growth factor receptor 2-positive tumors
      seemed to be most radioresistant, whereas triple-negative tumors had the largest
      effect on BCD. The effect of RT in the presumed low-risk luminal A-like tumors
      was excellent.

PMID- 28759348
TI  - Perceived Efficacy and Intentions Regarding Seeking Mental Healthcare: Impact of
      Deepika Padukone, A Bollywood Celebrity's Public Announcement of Struggle with
      Depression.
AB  - The current research examines the impact of Deepika Padukone's (one of the most
      popular Bollywood celebrities) public announcement of struggle with depression on
      people's perceived efficacy and intentions to seek help for mental healthcare. A
      survey conducted with 206 participants from India, the country with the highest
      depression rates in the world, revealed that parasocial interaction with the
      celebrity mediated the effect of exposure on intentions and efficacy perceptions
      regarding seeking mental healthcare. Our study expands the research on celebrity
      influence on health conditions in an international realm and in a mental health
      context. The findings have immense practical implications and may raise awareness
      about mental health in India given the popularity and reach of Bollywood among
      audiences in India and beyond, the level of stigmatization attached to mental
      health issues in India, and the lack of available resources for care.
      Theoretically, the study explores processes and effects of involvement with a
      celebrity and discusses potential implications for the behaviors related to
      health.

PMID- 28759349
TI  - Association Between Handgrip Muscle Strength and Cardiometabolic z-Score in
      Children 6 to 19 Years of Age: Results from the Canadian Health Measures Survey.
AB  - BACKGROUND: It is unclear if muscle strength, another index of fitness, which
      confers the protection from cardiometabolic risk in adults, is associated with
      similar protection in children and youth. The purpose of this study was to
      investigate the association between handgrip strength and cardiometabolic health
      in a large Canadian sample of children and youth. METHODS: We performed a cross
      sectional analysis of the Canadian sample of children and youth aged 6 to 19
      years (n = 1376) studied in the Canadian Health Measures Survey (cycles 1 and 2)
      between 2007 and 2011. The primary exposure variable, handgrip strength, was
      measured using a handgrip dynamometer. The primary outcome measure was a
      composite measure of cardiometabolic risk calculated as the sum of z-scores of
      the following variables: triglycerides, low high-density lipoprotein cholesterol,
      systolic and diastolic blood pressures, and hemoglobin A1c. All of the analyses
      were adjusted for confounders. RESULTS: The sample was on average 12.8 +/- 3.5
      years and displayed a body mass index (BMI) z-score of 0.5 +/- 1.2. In unadjusted
      analyses, handgrip strength was negatively associated with cardiometabolic z
      score (estimate = -0.013; P < 0.001). When results were adjusted for age, BMI z
      score, and cardiorespiratory fitness, the association was no longer significant;
      however, an interaction between handgrip strength, sex, and cardiometabolic z
      score was observed (estimate = -0.042; P < 0.001). When analyses were stratified
      by sex, handgrip strength was negatively associated with cardiometabolic z-score
      (estimate = -0.038; P < 0.001) in girls, but not in boys (estimate = 0.008; P =
      0.150). CONCLUSION: In a large sample of Canadian children and adolescents,
      handgrip strength was associated with cardiometabolic health in girls, but not in
      boys.

PMID- 28759351
TI  - Welcome from Norman Fry and Kalai Mathee, new co-Editors-in-Chief for the Journal
      of Medical Microbiology.

PMID- 28759350
TI  - Usutu Virus Antibodies in Blood Donors and Healthy Forestry Workers in the
      Lombardy Region, Northern Italy.
AB  - Usutu virus (USUV), a member of the genus Flavivirus, is known to circulate at
      low prevalence in Northern Italy, and has been reported to cause overt infection.
      USUV was first reported in Europe in 2001, but a retrospective study showed that
      it has been present in Italy at least since 1996. Seroprevalence data for USUV
      antibodies in sera are being collected in different European countries, showing
      circulation at low prevalence in human populations. Interestingly, two
      consecutive studies in Northern Italy indicate a possible increase in the
      presence of the virus, from 0% to 0.23% seroprevalence in blood donors. In this
      study, antibodies against USUV were measured in 3 consecutive blood samples
      collected from October 2014 to December 2015 from 33 forestry workers in the Po
      river valley, while samples from 200 blood donors from the same geographical area
      were tested in parallel. Neutralizing and IgG antibodies were found in six
      forestry workers (18.1%) and in two blood donors (1%). Our results indicate that
      USUV circulation in the examined area, part of a highly populated region in
      Northern Italy, is higher than expected. Healthy subjects exhibit a higher
      prevalence than what was found in a previous report in an adjoining region
      (0.23%), while the population at risk shows a much higher prevalence value
      (18.1%).

PMID- 28759353
TI  - Thank you and goodbye.

PMID- 28759354
TI  - Erratum.

PMID- 28759352
TI  - Minimum inhibitory concentration distributions for first- and second-line
      antimicrobials against Mycobacterium tuberculosis.
AB  - We report the range of minimum inhibitory concentrations for six antimicrobial
      drugs in 228 clinical Mycobacterium tuberculosis (MTB) isolates from three
      distinct groups of patients (unselected patients, patients at high risk of drug
      resistant TB and HIV-positive patients) in Lima, Peru. These data highlight the
      challenges of and discriminatory characteristics required for MTB drug
      susceptibility testing.

PMID- 28759355
TI  - Graphite design.

PMID- 28759356
TI  - Art and emotion in health care.

PMID- 28759357
TI  - Graphing individual cancer experiences with Cancergraph.

PMID- 28759358
TI  - The Hero.

PMID- 28759359
TI  - Embracing certainty.

PMID- 28759360
TI  - 39 degrees blue.

PMID- 28759361
TI  - Increasing global access to cancer care: models of care with non-oncologists as
      primary providers.

PMID- 28759362
TI  - Chilli-too hot to handle?

PMID- 28759363
TI  - Communicating cancer in the digital age.

PMID- 28759364
TI  - A bold expressionist Brand of art therapy.

PMID- 28759365
TI  - Bereaved and aggrieved in the age of social media.

PMID- 28759366
TI  - Calling time on the immunotherapy gold rush.

PMID- 28759367
TI  - A step towards predicting checkpoint inhibitor response in kidney cancer.

PMID- 28759369
TI  - High-dose chemotherapy and autologous stem-cell transplantation for DLBCL in the
      rituximab era.

PMID- 28759368
TI  - FLT3 inhibition in acute myeloid leukaemia.

PMID- 28759370
TI  - The science of precision prevention of cancer.

PMID- 28759371
TI  - Beyond bad luck: induced mutations and hallmarks of cancer.

PMID- 28759372
TI  - Prospective radiotherapy for patients with oropharyngeal carcinoma.

PMID- 28759373
TI  - Prospective radiotherapy for patients with oropharyngeal carcinoma - Authors'
      reply.

PMID- 28759374
TI  - Colorectal adenomas, surveillance, and cancer.

PMID- 28759375
TI  - Colorectal adenomas, surveillance, and cancer - Authors' reply.

PMID- 28759376
TI  - Evidence-based management of adult patients with diffuse glioma.

PMID- 28759377
TI  - Evidence-based management of adult patients with diffuse glioma - Authors' reply.

PMID- 28759378
TI  - Cancer in the Renaissance court of Naples.

PMID- 28759380
TI  - Correction to Lancet Oncol 2017; 18: 1022-39.

PMID- 28759379
TI  - Correction to Lancet Oncol 2017; 18: 1040-48.

PMID- 28759381
TI  - Correction to Lancet Oncol 2017; 18: 917-28.

PMID- 28759382
TI  - Correction to Lancet Oncol 2017; 18: 556-57.

PMID- 28759383
TI  - Correction to Lancet Oncol 2017; 18: 732-42.

PMID- 28759384
TI  - Cardiotoxic effects of anthracycline-based therapy: what is the evidence and what
      are the potential harms?
AB  - Despite the known cardiotoxic effects of doxorubicin and other anthracyclines, no
      evidence-based guidelines exist for the surveillance and prevention of
      chemotherapy-induced cardiotoxicity in adult survivors of breast cancer who have
      had limited previous doses of anthracyclines (ie, total cumulative dose 240
      mg/m2), or limited-dose anthracyclines followed by trastuzumab-based regimens.
      Nonetheless, some national and international cardio-oncology and cardiac-imaging
      organisations recommend increased cardiac surveillance during or after treatment,
      measurement of cardiac biomarkers and other surrogate endpoints, and in some
      cases initiation of cardioprotective drug therapy in asymptomatic women. However,
      two unintended potential harms of such approaches are medicalisation (definition
      and treatment of subclinical heart problems without high-level evidence for a
      consequent reduction in the incidence of subsequent heart failure or cardiac
      deaths) and increased health-care costs when the value of providing that care is
      unknown. Whether existing cardio-oncology or imaging guideline recommendations
      will provide increased value or cause increased distress and lower health-related
      quality of life is unknown. Further research is needed to assess the long-term
      benefits, harms, and value of expanded cardiac surveillance, use of surrogate
      cardiac biomarkers, and prophylactic cardioprotective therapy in asymptomatic
      women with limited exposure to anthracyclines.

PMID- 28759385
TI  - Physical activity, sedentary behaviour, diet, and cancer: an update and emerging
      new evidence.
AB  - The lifestyle factors of physical activity, sedentary behaviour, and diet are
      increasingly being studied for their associations with cancer. Physical activity
      is inversely associated with and sedentary behaviour is positively (and
      independently) associated with an increased risk of more than ten types of
      cancer, including colorectal cancer (and advanced adenomas), endometrial cancers,
      and breast cancer. The most consistent dietary risk factor for premalignant and
      invasive breast cancer is alcohol, whether consumed during early or late adult
      life, even at low levels. Epidemiological studies show that the inclusion of
      wholegrain, fibre, fruits, and vegetables within diets are associated with
      reduced cancer risk, with diet during early life (age <8 years) having the
      strongest apparent association with cancer incidence. However, randomised
      controlled trials of diet-related factors have not yet shown any conclusive
      associations between diet and cancer incidence. Obesity is a key contributory
      factor associated with cancer risk and mortality, including in dose-response
      associations in endometrial and post-menopausal breast cancer, and in degree and
      duration of fatty liver disease-related hepatocellular carcinoma. Obesity
      produces an inflammatory state, characterised by macrophages clustered around
      enlarged hypertrophied, dead, and dying adipocytes, forming crown-like
      structures. Increased concentrations of aromatase and interleukin 6 in inflamed
      breast tissue and an increased number of macrophages, compared with healthy
      tissue, are also observed in women with normal body mass index, suggesting a
      metabolic obesity state. Emerging randomised controlled trials of physical
      activity and dietary factors and mechanistic studies of immunity, inflammation,
      extracellular matrix mechanics, epigenetic or transcriptional regulation, protein
      translation, circadian disruption, and interactions of the multibiome with
      lifestyle factors will be crucial to advance this field.

PMID- 28759386
TI  - Preventive therapy for cancer.
AB  - Therapeutic cancer prevention is a developing area that can gain a lot from the
      successes in the prevention of cardiovascular diseases. Although weight control
      and physical activity are important in the prevention of both diseases, several
      other preventive measures exist. Low-dose aspirin for cancer prevention is often
      cited as the most important approach in terms of population benefit, and should
      be offered to those older than 50 years of age without hypertension or risk
      factors for gastrointestinal bleeding. Universal vaccination against the human
      papillomavirus, ideally with the nine-valent vaccine, also offers substantial
      benefits for the whole population if given before infection occurs (ie, typically
      at age 12-14 years). Other therapies, such as anti-oestrogen drugs for breast
      cancer prevention, should be targeted to high-risk groups to maintain a
      favourable benefit-risk ratio. Better algorithms for identification and improved
      platforms to reach these groups, such as during a screening visit, remain a key
      priority to allow existing knowledge to inform public health. Many other
      promising compounds have been identified, often as components of food, but
      results suggesting increased disease incidence with beta carotene and vitamin E
      administration indicate that such treatments need rigorous evaluation before
      acceptance.

PMID- 28759387
TI  - The role of government and regulation in cancer prevention.
AB  - The world population is ageing and increasing in size. As a result, the numbers
      of people diagnosed with and dying of cancer are increasing. Cancer is also a
      growing problem in developing countries. Government, be it local, state,
      provincial, national, or even a union of nations, has clear roles in the control
      of cancer. It is widely appreciated that much of the research that has defined
      the causes and treatment of cancer was, and is, government funded. Less
      appreciated, the body of work about how to control cancer shows the importance of
      an environment that encourages individuals to adopt healthy behaviours, and
      government has a vitally important role. Through regulation, education, and
      support programmes, governments can create an environment in which tobacco use is
      reduced and citizens maintain good levels of physical activity, healthy
      bodyweight, and good nutrition. Cancer prevention and the creation of a culture
      of health is an essential mission of government, beyond that of the traditional
      health-focused departments such as health ministries; it is in the domain of
      governmental agencies involved in environmental protection, occupational safety,
      and transportation. Cancer prevention and health promotion are also in the realm
      of the zoning board, the board of education, and the board of health.

PMID- 28759389
TI  - Tumour d'emblee.

PMID- 28759388
TI  - Genomic approaches to accelerate cancer interception.
AB  - Although major advances have been reported in the last decade in the treatment of
      late-stage cancer with targeted and immune-based therapies, there is a crucial
      unmet need to develop new approaches to improve the prevention and early
      detection of cancer. Advances in genomics and computational biology offer
      unprecedented opportunities to understand the earliest molecular events
      associated with carcinogenesis, enabling novel strategies to intercept the
      development of invasive cancers. This Series paper will highlight emerging big
      data genomic approaches with the potential to accelerate advances in cancer
      prevention, screening, and early detection across various tumour types, and the
      challenges inherent in the development of these tools for clinical use. Through
      coordinated multicentre consortia, these genomic approaches are likely to
      transform the landscape of cancer interception in the coming years.

PMID- 28759390
TI  - Cholestasis and Hepatic Iron Deposition in an Infant With Complex Glycerol Kinase
      Deficiency.
AB  - We present a 6-week-old male infant with persistent hyperbilirubinemia,
      hypertriglyceridemia, elevated creatine kinase levels, and transaminitis since
      the second week of life. When he developed hyperkalemia, clinical suspicion was
      raised for adrenal insufficiency despite hemodynamic stability. A full endocrine
      workup revealed nearly absent adrenocorticotropic hormone. Coupled with his
      persistent hypertriglyceridemia (peak of 811 mg/dL) and elevated creatine kinase
      levels (>20 000 U/L), his corticotropin level lead to a clinical diagnosis of
      complex glycerol kinase deficiency (GKD), also known as Xp21 deletion syndrome.
      This complex disorder encompasses the phenotype of Duchenne muscular dystrophy,
      GKD, and congenital adrenal hypoplasia due to the deletion of 3 contiguous
      genetic loci on the X chromosome. Our case exemplifies the presentation of this
      disorder and highlights the important lesson of distinguishing between adrenal
      hypoplasia congenita and congenital adrenal hyperplasia, as well as the sometimes
      subtle presentation of adrenal insufficiency. To our knowledge, it is also the
      first reported case of complex GKD deficiency with the additional finding of
      hepatic iron deposition, which may indicate a potential area for exploration
      regarding the pathogenesis of liver injury and cholestasis seen in cortisol
      related endocrinopathies.

PMID- 28759391
TI  - Case Report of a Hypobaric Chamber Fitness to Fly Test in a Child With Severe
      Cystic Lung Disease.
AB  - Patients with severe cystic lung disease are considered to be at risk for cyst
      rupture during air travel because of the possibility of increase in cyst size and
      impaired equilibration of pressure between the cysts and other parts of the lung.
      This may have clinically devastating consequences for the patient but may also
      result in significant costs for emergency alteration of flight schedule. We
      report the use of a hypobaric chamber to simulate cabin pressure changes
      encountered on a commercial flight to assess the safety to fly of a child with
      severe cystic lung disease secondary to Langerhans cell histiocytosis. The test
      did not result in an air leak, and the child subsequently undertook air travel
      without mishap. This is the first reported use of a hypobaric chamber test in a
      child with severe cystic lung disease. This test has the potential to be used as
      a fitness to fly test in children at risk for air leak syndromes who are being
      considered for air travel.

PMID- 28759392
TI  - A 3-Week-Old With an Isolated "Blueberry Muffin" Rash.
AB  - A 3-week-old boy, former 39-week term infant, presented to the emergency
      department with a rash. One week before presentation, he developed dark, purple
      papules on his forehead, which then spread to the abdomen and inguinal regions.
      Throughout this time, he was eating well, gaining weight, developing
      appropriately, and was afebrile without cough, congestion, or rhinorrhea. On
      presentation, the patient was well appearing with normal vital signs. His weight
      was 4.83 kg (86th percentile for age), his length was 56 cm (47th percentile for
      age), and his head circumference was 37 cm (62nd percentile for age). On skin
      examination, there were scattered purpuric papules and macules on the scalp,
      forehead, trunk, abdomen, and inguinal region. Initial laboratory studies were
      remarkable only for mild anemia. Our expert panel examines the case, offers a
      differential for a child with a "blueberry muffin" rash, and makes diagnostic
      considerations.

PMID- 28759393
TI  - Chorioamnionitis and Management of Asymptomatic Infants >=35 Weeks Without
      Empiric Antibiotics.
AB  - BACKGROUND AND OBJECTIVE: Management of asymptomatic infants >=35 weeks'
      gestation born to mothers with chorioamnionitis remains controversial, with many
      clinicians considering the need for changes to the current guidelines. The study
      objective was to evaluate the outcomes of asymptomatic chorioamnionitis-exposed
      neonates without the use of immediate empirical antibiotics. METHODS: A
      retrospective data review was conducted from May 2008 to December 2014, including
      asymptomatic infants >=35 weeks' gestation with a maternal diagnosis of clinical
      chorioamnionitis. RESULTS: A total of 240 asymptomatic infants with
      chorioamnionitis exposure were identified. The majority of asymptomatic
      chorioamnionitis-exposed infants, 162 (67.5%), remained well in the mother-infant
      unit with a median stay of 2 days. There were 78 (32.5%) infants admitted to the
      NICU and exposed to antibiotics due to abnormal laboratory data or development of
      clinical symptoms. Of those infants admitted to the NICU, 19 (24%) received
      antibiotics for <72 hours, 47 (60%) were treated for culture-negative clinical
      sepsis, and 12 (15%) for culture-positive sepsis, with a median NICU stay of 7
      days. CONCLUSIONS: Nonroutine use of empirical antibiotics in asymptomatic
      newborns >=35 weeks' gestation with maternal chorioamninonitis prevented NICU
      admission in two-thirds of these infants. This prevented unnecessary antibiotic
      exposure, increased hospitalization costs, and disruption of mother-infant
      bonding and breastfeeding. Laboratory evaluation and clinical observation without
      immediate antibiotic administration may be incorporated into a management
      approach in asymptomatic chorioamnionitis-exposed neonates. Additional studies
      are needed to establish the safety of this approach.

PMID- 28759394
TI  - Impact of Prolonged Breastfeeding on Dental Caries: A Population-Based Birth
      Cohort Study.
AB  - BACKGROUND: Few studies have assessed the effect of breastfeeding, bottle
      feeding, and sugar consumption on children's dental caries. We investigated
      whether the duration of breastfeeding is a risk factor for dental caries in the
      primary dentition, independently of sugar consumption. METHODS: An oral health
      study (n = 1303) nested in a birth cohort study was carried out in southern
      Brazil. The average number of decayed, missing, and filled primary tooth surfaces
      (dmfs) and severe early childhood caries (S-ECC: dmfs >=6) were investigated at
      age 5 years. Breastfeeding was the main exposure collected at birth and at 3, 12,
      and 24 months of age. Data on sugar consumption were collected at 24, 48, and 60
      months of age. Marginal structural modeling was used to estimate the controlled
      direct effect of breastfeeding (0-12, 13-23, and >=24 months) on dmfs and on S
      ECC. RESULTS: The prevalence of S-ECC was 23.9%. The mean number of dmfs was
      4.05. Children who were breastfed for >=24 months had a higher number of dmfs
      (mean ratio: 1.9; 95% confidence interval: 1.5-2.4) and a 2.4 times higher risk
      of having S-ECC (risk ratio: 2.4; 95% confidence interval: 1.7-3.3) than those
      who were breastfed up to 12 months of age. Breastfeeding between 13 and 23 months
      had no effect on dental caries. CONCLUSIONS: Prolonged breastfeeding increases
      the risk of having dental caries. Preventive interventions for dental caries
      should be established as early as possible because breastfeeding is beneficial
      for children's health. Mechanisms underlying this process should be investigated
      more deeply.

PMID- 28759395
TI  - Childhood Illness and the Gender Gap in Adolescent Education in Low- and Middle
      Income Countries.
AB  - BACKGROUND: Achieving gender equality in education is an important development
      goal. We tested the hypothesis that the gender gap in adolescent education is
      accentuated by illnesses among young children in the household. METHODS: Using
      Demographic and Health Surveys on 41 821 households in 38 low- and middle-income
      countries, we used linear regression to estimate the difference in the
      probability adolescent girls and boys were in school, and how this gap responded
      to illness episodes among children <5 years old. To test the hypothesis that
      investments in child health are related to the gender gap in education, we
      assessed the relationship between the gender gap and national immunization
      coverage. RESULTS: In our sample of 120 708 adolescent boys and girls residing in
      38 countries, girls were 5.08% less likely to attend school than boys in the
      absence of a recent illness among young children within the same household (95%
      confidence interval [CI], 5.50%-4.65%). This gap increased to 7.77% (95% CI,
      8.24%-7.30%) and 8.53% (95% CI, 9.32%-7.74%) if the household reported 1 and 2 or
      more illness episodes, respectively. The gender gap in schooling in response to
      illness was larger in households with a working mother. Increases in child
      vaccination rates were associated with a closing of the gender gap in schooling
      (correlation coefficient = 0.34, P = .02). CONCLUSIONS: Illnesses among children
      strongly predict a widening of the gender gap in education. Investments in early
      childhood health may have important effects on schooling attainment for
      adolescent girls.

PMID- 28759396
TI  - Pictograms, Units and Dosing Tools, and Parent Medication Errors: A Randomized
      Study.
AB  - BACKGROUND AND OBJECTIVES: Poorly designed labels and dosing tools contribute to
      dosing errors. We examined the degree to which errors could be reduced with
      pictographic diagrams, milliliter-only units, and provision of tools more closely
      matched to prescribed volumes. METHODS: This study involved a randomized
      controlled experiment in 3 pediatric clinics. English- and Spanish-speaking
      parents (n = 491) of children <=8 years old were randomly assigned to 1 of 4
      groups and given labels and dosing tools that varied in label instruction format
      (text and pictogram, or text only) and units (milliliter-only ["mL"] or
      milliliter/teaspoon ["mL/tsp"]). Each parent measured 9 doses of liquid
      medication (3 amounts [2, 7.5, and 10 mL] and 3 tools [1 cup, 2 syringes (5- and
      10-mL capacities)]) in random order. The primary outcome was dosing error (>20%
      deviation), and large error (>2* dose). RESULTS: We found that 83.5% of parents
      made >=1 dosing error (overdosing was present in 12.1% of errors) and 29.3% of
      parents made >=1 large error (>2* dose). The greatest impact on errors resulted
      from the provision of tools more closely matched to prescribed dose volumes. For
      the 2-mL dose, the fewest errors were seen with the 5-mL syringe (5- vs 10-mL
      syringe: adjusted odds ratio [aOR] = 0.3 [95% confidence interval: 0.2-0.4]; cup
      versus 10-mL syringe: aOR = 7.5 [5.7-10.0]). For the 7.5-mL dose, the fewest
      errors were with the 10-mL syringe, which did not necessitate measurement of
      multiple instrument-fulls (5- vs 10-mL syringe: aOR = 4.0 [3.0-5.4]; cup versus
      10-mL syringe: aOR = 2.1 [1.5-2.9]). Milliliter/teaspoon was associated with more
      errors than milliliter-only (aOR = 1.3 [1.05-1.6]). Parents who received text
      only (versus text and pictogram) instructions or milliliter/teaspoon (versus
      milliliter-only) labels and tools made more large errors (aOR = 1.9 [1.1-3.3],
      aOR = 2.5 [1.4-4.6], respectively). CONCLUSIONS: Provision of dosing tools more
      closely matched to prescribed dose volumes is an especially promising strategy
      for reducing pediatric dosing errors.

PMID- 28759397
TI  - Prematurity and Sudden Unexpected Infant Deaths in the United States.
AB  - BACKGROUND AND OBJECTIVES: Prematurity, a strong risk factor for sudden
      unexpected infant death (SUID), was addressed in recommendations by the American
      Academy of Pediatrics in 2011 for safe sleep education in NICUs. We documented
      associations between gestational age (GA) and SUID subsequent to these
      guidelines. METHODS: Using the 2012-2013 US linked infant birth and death
      certificate period files, we documented rates per live births of sudden infant
      death syndrome, ill-defined and unspecified causes, accidental suffocation and
      strangulation in bed, and overall SUID by GA in postneonatal, out-of-hospital,
      and autopsied cases; compared survivors and cases; and estimated logistic
      regression models of associations between GA and SUID. RESULTS: SUID cases were
      more likely than survivors to be <37 weeks' GA (22.61% vs 10.79%; P < .0001).
      SUID rates were 2.68, 1.94, 1.46, 1.16, 0.73, and 0.51 per 1000 live births for
      24 to 27, 28 to 31, 32 to 33, 34 to 36, 37 to 38, and 39 to 42 weeks' GA,
      respectively. Logistic regression models additionally indicated declines in the
      risk for SUID as GA increased. Prenatal smoking, inadequate prenatal care, and
      demographics associated with poverty were strongly associated with SUID.
      CONCLUSIONS: Despite the 2011 American Academy of Pediatrics recommendations for
      increased safe sleep education in the NICUs, SUID rates were inversely associated
      with GA in 2012 to 2013, suggesting that risk of SUID associated with prematurity
      has multiple etiologies requiring continued investigation, including biological
      vulnerabilities and the efficacy of NICU education programs, and that strategies
      to reduce SUID should be multifaceted.

PMID- 28759398
TI  - Early Sign Language Exposure and Cochlear Implantation Benefits.
AB  - BACKGROUND: Most children with hearing loss who receive cochlear implants (CI)
      learn spoken language, and parents must choose early on whether to use sign
      language to accompany speech at home. We address whether parents' use of sign
      language before and after CI positively influences auditory-only speech
      recognition, speech intelligibility, spoken language, and reading outcomes.
      METHODS: Three groups of children with CIs from a nationwide database who
      differed in the duration of early sign language exposure provided in their homes
      were compared in their progress through elementary grades. The groups did not
      differ in demographic, auditory, or linguistic characteristics before
      implantation. RESULTS: Children without early sign language exposure achieved
      better speech recognition skills over the first 3 years postimplant and exhibited
      a statistically significant advantage in spoken language and reading near the end
      of elementary grades over children exposed to sign language. Over 70% of children
      without sign language exposure achieved age-appropriate spoken language compared
      with only 39% of those exposed for 3 or more years. Early speech perception
      predicted speech intelligibility in middle elementary grades. Children without
      sign language exposure produced speech that was more intelligible (mean = 70%)
      than those exposed to sign language (mean = 51%). CONCLUSIONS: This study
      provides the most compelling support yet available in CI literature for the
      benefits of spoken language input for promoting verbal development in children
      implanted by 3 years of age. Contrary to earlier published assertions, there was
      no advantage to parents' use of sign language either before or after CI.

PMID- 28759399
TI  - Time-Use Patterns and Health-Related Quality of Life in Adolescents.
AB  - OBJECTIVES: To describe 24-hour time-use patterns and their association with
      health-related quality of life (HRQoL) in early adolescence. METHODS: The Child
      Health CheckPoint was a cross-sectional study nested between Waves 6 and 7 of the
      Longitudinal Study of Australian Children. The participants were 1455 11- to 12
      year-olds (39% of Wave 6; 51% boys). The exposure was 24-hour time use measured
      across 259 activities using the Multimedia Activity Recall for Children and
      Adolescents. "Average" days were generated from 1 school and 1 nonschool day.
      Time-use clusters were derived from cluster analysis with compositional inputs.
      The outcomes were self-reported HRQoL (Physical and Psychosocial Health [PedsQL]
      summary scores; Child Health Utility 9D [CHU9D] health utility). RESULTS: Four
      time-use clusters emerged: "studious actives" (22%; highest school-related time,
      low screen time), "techno-actives" (33%; highest physical activity, lowest school
      related time), "stay home screenies" (23%; highest screen time, lowest passive
      transport), and "potterers" (21%; low physical activity). Linear regression
      models, adjusted for a priori confounders, showed that compared with the
      healthiest "studious actives" (mean [SD]: CHU9D 0.84 [0.14], PedsQL physical 86.8
      [10.8], PedsQL psychosocial 79.9 [12.6]), HRQoL in "potterers" was 0.2 to 0.5 SDs
      lower (mean differences [95% confidence interval]: CHU9D -0.03 [-0.05 to -0.00],
      PedsQL physical -5.5 [-7.4 to -3.5], PedsQL psychosocial -5.8 [-8.0 to -3.5]).
      CONCLUSIONS: Discrete time-use patterns exist in Australian young adolescents.
      The cluster characterized by low physical activity and moderate screen time was
      associated with the lowest HRQoL. Whether this pattern translates into precursors
      of noncommunicable diseases remains to be determined.

PMID- 28759400
TI  - Body Composition in Adolescents During Treatment With Selective Serotonin
      Reuptake Inhibitors.
AB  - OBJECTIVES: To examine the independent contribution of major depressive disorder
      (MDD), generalized anxiety disorder (GAD), and selective serotonin reuptake
      inhibitors (SSRIs) to changes in body composition in older adolescents. METHODS:
      Medically healthy 15- to 20-year-olds who were unmedicated or within 1 month of
      starting an SSRI were prospectively followed. Psychiatric functioning and
      medication treatment were assessed monthly. Body Mass Index (BMI) was measured
      every 4 months. Every 8 months, a whole-body dual-energy radiograph
      absorptiometry scan was obtained to determine lean BMI, fat mass index, and
      visceral fat mass. Linear mixed effects regression analysis examined associations
      between MDD, GAD, and SSRI use variables and body composition measures. RESULTS:
      Over 1.51 +/- 0.76 years of follow-up, 264 participants contributed 805
      observations. After adjusting for age, sex, physical activity, dietary intake,
      and time in the study, MDD severity was inversely associated, prospectively, with
      BMI, fat mass index, and lean BMI z scores, whereas cumulative SSRI treatment
      duration and dose were positively associated with these outcomes. GAD severity
      and diagnosis were not significantly associated with any body composition
      outcome. Moreover, citalopram and escitalopram were most strongly associated with
      the increase in all body composition measures, including visceral fat mass,
      whereas the associations with fluoxetine were somewhat weaker. Sertraline was not
      different from no SSRI treatment. CONCLUSIONS: Depression severity was associated
      with a decrease in measures of body composition in older adolescents over a mean
      of 1.5 years, whereas SSRI treatment was positively associated with these
      outcomes, with differential effects across treatment groups.

PMID- 28759401
TI  - The Safety of Medications in Pregnant Women: An Opportunity to Use Database
      Studies.

PMID- 28759402
TI  - Access to Emergency Contraception After Removal of Age Restrictions.
AB  - BACKGROUND: Levonorgestrel emergency contraception (EC) is safe and effective for
      postcoital pregnancy prevention. Starting in 2013, the US Food and Drug
      Administration removed age restrictions, enabling EC to be sold over the counter
      to all consumers. We sought to compare the availability and access for female
      adolescents with the 2012 study, using the same study design. METHODS: Female
      mystery callers posing as 17-year-old adolescents in need of EC used standardized
      scripts to telephone 979 pharmacies in 5 US cities. Using 2015 estimated census
      data and the federal poverty level, we characterized income levels of pharmacy
      neighborhoods. RESULTS: Of 979 pharmacies, 827 (83%) indicated that EC was
      available. This proportion did not vary by pharmacy neighborhood income level,
      nor was significantly different from the 2012 study (P = .78). When examining
      access, 8.3% of the pharmacies reported it was impossible to obtain EC under any
      circumstances, which occurred more often in low-income neighborhoods (10.3% vs
      6.3%, adjusted odds ratio 1.5; 95% confidence interval 1.20-1.94). This was not
      significantly different from 2012 (P = .66). Correct information regarding over
      the-counter access was conveyed only 51.6% of the time; accuracy did not differ
      by pharmacy's neighborhood income (47.9% vs 55.3%, adjusted odds ratio 0.89; 95%
      confidence interval 0.71-1.11) and was not significantly different from 2012 (P =
      .37). CONCLUSIONS: A majority of pharmacies have EC available; however, barriers
      to and disparities in access for adolescents persist and have not changed since
      the previous study despite regulatory changes that were designed to improve
      access to EC.

PMID- 28759404
TI  - Upper Respiratory Infections and Airway Adverse Events in Pediatric Procedural
      Sedation.
AB  - BACKGROUND: Upper respiratory infections (URIs) are associated with airway
      adverse events (AAEs) during general anesthesia. There have been no large studies
      examining the relationship between URIs and AAEs during pediatric procedural
      sedation. We hypothesized that there would be a relationship between URI status
      and AAEs in pediatric procedural sedation. METHODS: We examined prospectively
      collected data from the Pediatric Sedation Research Consortium database. Specific
      questions regarding URI status were added to the database to facilitate our
      analysis. Characteristics of patients, procedure types, adjunctive medications,
      adverse events, and airway interventions (AIs) were reported. We performed
      bivariate analysis of adverse events and URI status, then used a multivariable
      logistic regression model to assess the relationship between URI status and
      adverse events. We examined the secondary outcome of AI similarly. RESULTS: Of
      the 105 728 sedations entered into the Pediatric Sedation Research Consortium
      database during the study period, we were able to use 83 491 for analysis.
      Controlling for multiple patient, drug, and procedure characteristics, recent and
      current URI were associated with increased frequency of AAEs. In general, the
      frequency of AAEs and AIs increased from recent URI, to current URI-clear
      secretions to current URI-thick secretions. We did not find a relationship
      between URI status and non-AAEs. CONCLUSIONS: URI status is associated with a
      statistically significant increase in frequency of AAEs and AI during pediatric
      procedural sedation for the population sedated by our consortium. Although URI
      status merits consideration in determining potential risk for sedation, rates of
      some AAEs and AIs remained low regardless of URI status.

PMID- 28759403
TI  - Metformin for Obesity in Prepubertal and Pubertal Children: A Randomized
      Controlled Trial.
AB  - OBJECTIVES: Metformin has shown its effectiveness in treating obesity in adults.
      However, little research has been conducted in children, with a lack of attention
      on pubertal status. The objectives were to determine whether oral metformin
      treatment reduces BMI z score, cardiovascular risk, and inflammation biomarkers
      in children who are obese depending on pubertal stage and sex. METHODS: This was
      a randomized, prospective, double-blind, placebo-controlled, multicenter trial,
      stratified according to pubertal stage and sex, conducted at 4 Spanish clinical
      hospitals. Eighty prepubertal and 80 pubertal nondiabetic children who were obese
      aged 7 to 14 years with a BMI >95th percentiles were recruited. The intervention
      included 1 g/d of metformin versus placebo for 6 months. The primary outcome was
      a reduction in BMI z score. Secondary outcomes comprised insulin resistance,
      cardiovascular risk, and inflammation biomarkers. RESULTS: A total of 140
      children completed the study (72 boys). Metformin decreased the BMI z score
      versus placebo in the prepubertal group (-0.8 and -0.6, respectively; difference,
      0.2; P = .04). Significant increments were observed in prepubertal children
      treated with metformin versus placebo recipients in the quantitative insulin
      sensitivity check index (0.010 and -0.007; difference, 0.017; P = .01) and the
      adiponectin-leptin ratio (0.96 and 0.15; difference, 0.81; P = .01) and declines
      in interferon-gamma (-5.6 and 0; difference, 5.6; P = .02) and total plasminogen
      activator inhibitor-1 (-1.7 and 2.4; difference, 4.1; P = .04). No serious
      adverse effects were reported. CONCLUSIONS: "Metformin decreased the BMI z score
      and improved inflammatory and cardiovascular-related obesity parameters only in
      prepubertal children, but a differential effect of metformin was not observed in
      prepubertal compared to pubertal children. Nevertheless, the doses per kilogram
      of weight administrated may have had an impact on the metformin effect. Further
      investigations are necessary."

PMID- 28759405
TI  - Outcomes of Nonoperative Management of Uncomplicated Appendicitis.
AB  - BACKGROUND AND OBJECTIVES: Nonoperative management (NOM) of uncomplicated
      pediatric appendicitis has promise but remains poorly studied. NOM may lead to an
      increase in resource utilization. Our objective was to investigate the trends in
      NOM for uncomplicated appendicitis and study the relevant clinical outcomes
      including subsequent appendectomy, complications, and resource utilization.
      METHODS: Retrospective analysis of administrative data from 45 US pediatric
      hospitals. Patients <19 years of age presenting to the emergency department (ED)
      with appendicitis between 2010 and 2016 were studied. NOM was defined by an ED
      visit for uncomplicated appendicitis treated with antibiotics and the absence of
      appendectomy at the index encounter. The main outcomes included trends in NOM
      among children with uncomplicated appendicitis and frequency of subsequent
      diagnostic imaging, ED visits, hospitalizations, and appendectomy during 12-month
      follow-up. RESULTS: 99 001 children with appendicitis were identified, with a
      median age of 10.9 years. Sixty-six percent were diagnosed with nonperforated
      appendicitis, of which 4190 (6%) were managed nonoperatively. An increasing
      number of nonoperative cases were observed over 6 years (absolute difference,
      +20.4%). During the 12-month follow-up period, NOM patients were more likely to
      have the following: advanced imaging (+8.9% [95% confidence interval (CI) 7.6% to
      10.3%]), ED visits (+11.2% [95% CI 9.3% to 13.2%]), and hospitalizations (+43.7%
      [95% CI 41.7% to 45.8%]). Among patients managed nonoperatively, 46% had a
      subsequent appendectomy. CONCLUSIONS: A significant increase in NOM of
      nonperforated appendicitis was observed over 6 years. Patients with NOM had more
      subsequent ED visits and hospitalizations compared with those managed operatively
      at the index visit. A substantial proportion of patients initially managed
      nonoperatively eventually had an appendectomy.

PMID- 28759406
TI  - Variations in Cause-of-Death Determination for Sudden Unexpected Infant Deaths.
AB  - OBJECTIVES: To quantify and describe variation in cause-of-death certification of
      sudden unexpected infant deaths (SUIDs) among US medical examiners and coroners.
      METHODS: From January to November 2014, we conducted a nationally representative
      survey of US medical examiners and coroners who certify infant deaths. Two-stage
      unequal probability sampling with replacement was used. Medical examiners and
      coroners were asked to classify SUIDs based on hypothetical scenarios and to
      describe the evidence considered and investigative procedures used for cause-of
      death determination. Frequencies and weighted percentages were calculated.
      RESULTS: Of the 801 surveys mailed, 60% were returned, and 377 were deemed
      eligible and complete. Medical examiners and coroners classification of infant
      deaths varied by scenario. For 3 scenarios portraying potential airway
      obstruction and negative autopsy findings, 61% to 69% classified the death as
      suffocation/asphyxia. In the last scenario, which portrayed a healthy infant in a
      safe sleep environment with negative autopsy findings, medical examiners and
      coroners classified the death as sudden infant death syndrome (38%) and SUID
      (30%). Reliance on investigative procedures to determine cause varied, but 94%
      indicated using death scene investigations, 88% full autopsy, 85% toxicology
      analyses, and 82% medical history review. CONCLUSIONS: US medical examiners and
      coroners apply variable practices to classify and investigate SUID, and thus,
      they certify the same deaths differently. This variability influences
      surveillance and research, impacts true understanding of infant mortality causes,
      and inhibits our ability to accurately monitor and ultimately prevent future
      deaths. Findings may inform future strategies for promoting standardized
      practices for SUID classification.

PMID- 28759408
TI  - Variation in Formula Supplementation of Breastfed Newborn Infants in New York
      Hospitals.
AB  - OBJECTIVES: We examined the variation between 126 New York hospitals in formula
      supplementation among breastfed infants after adjusting for socioeconomic,
      maternal, and infant factors and stratifying by level of perinatal care. METHODS:
      We used 2014 birth certificate data for 160 911 breastfed infants to calculate
      hospital-specific formula supplementation percentages by using multivariable
      hierarchical logistic regression models. RESULTS: Formula supplementation
      percentages varied widely among hospitals, from 2.3% to 98.3%, and was lower
      among level 1 hospitals (18.2%) than higher-level hospitals (50.6%-57.0%).
      Significant disparities in supplementation were noted for race and ethnicity
      (adjusted odds ratios [aORs] were 1.54-2.05 for African Americans, 1.85-2.74 for
      Asian Americans, and 1.25-2.16 for Hispanics, compared with whites), maternal
      education (aORs were 2.01-2.95 for <=12th grade, 1.74-1.85 for high school or
      general education development, and 1.18-1.28 for some college or a college
      degree, compared with a Master's degree), and insurance coverage (aOR was 1.27
      1.60 for Medicaid insurance versus other). Formula supplementation was higher
      among mothers who smoked, had a cesarean delivery, or diabetes. At all 4 levels
      of perinatal care, there were exemplar hospitals that met the HealthyPeople 2020
      supplementation goal of <=14.2%. After adjusting for individual risk factors, the
      hospital-specific, risk-adjusted supplemental formula percentages still revealed
      a wide variation. CONCLUSIONS: A better understanding of the exemplar hospitals
      could inform future efforts to improve maternity care practices and breastfeeding
      support to reduce unnecessary formula supplementation, reduce disparities,
      increase exclusive breastfeeding and breastfeeding duration, and improve maternal
      and child health outcomes.

PMID- 28759407
TI  - Mother-Infant Room-Sharing and Sleep Outcomes in the INSIGHT Study.
AB  - OBJECTIVES: The American Academy of Pediatrics recommends infant-parent room
      sharing until age 1. We assessed the association between room-sharing and sleep
      outcomes. METHODS: The Intervention Nurses Start Infants Growing on Healthy
      Trajectories study is an obesity prevention trial comparing a responsive
      parenting intervention with a safety control among primiparous mother-infant
      dyads. Mothers completed the Brief Infant Sleep Questionnaire at 4, 9, 12, and 30
      months. Reported sleep duration and overnight behaviors, adjusted for
      intervention group, were compared among early independent sleepers (own room <4
      months), later independent sleepers (own room between 4 and 9 months), and room
      sharers at 9 months. RESULTS: At 4 months, reported overnight sleep duration was
      similar between groups, but compared with room-sharers, early independent
      sleepers had better sleep consolidation (longest stretch: 46 more minutes, P =
      .02). At 9 months, early independent sleepers slept 40 more minutes nightly than
      room-sharers and 26 more minutes than later independent sleepers (P = .008). The
      longest stretch for early independent sleepers was 100 and 45 minutes more than
      room-sharers and later independent sleepers, respectively (P = .01). At 30
      months, infants sleeping independently by 9 months slept >45 more minutes nightly
      than those room-sharing at 9 months (P = .004). Room-sharers had 4 times the odds
      of transitioning to bed-sharing overnight at both 4 and 9 months (P < .01 for
      both). CONCLUSIONS: Room-sharing at ages 4 and 9 months is associated with less
      nighttime sleep in both the short and long-term, reduced sleep consolidation, and
      unsafe sleep practices previously associated with sleep-related death.

PMID- 28759409
TI  - Head Growth Trajectory and Neurodevelopmental Outcomes in Preterm Neonates.
AB  - OBJECTIVES: To evaluate the association between head growth (HG) during neonatal
      and postdischarge periods and neurodevelopmental outcomes of preterm neonates of
      <29 weeks gestational age. METHODS: We conducted a retrospective cohort study of
      infants <29 weeks gestational?age admitted between 2009 and 2011 to participating
      Canadian Neonatal Network?units and followed by Canadian Neonatal Follow-Up
      Network clinics. Differences in head circumference (DeltaHC) z score were
      calculated for 3 time periods, which include admission to discharge, discharge to
      follow-up at 16-36 months, and admission to follow-up. These were categorized in
      1 reference group (DeltaHC z score between -1 and +1) and 4 study groups (DeltaHC
      z score of <-2, between -2 to -1, +1 to +2, and >+2). Neurodevelopmental outcomes
      were compared with the reference group. RESULTS: 1973 infants met the inclusion
      criteria. Poor HG occurred frequently during the NICU admission (DeltaHC z score
      <-2 in 24% infants versus 2% infants post-discharge) with a period of "catch-up"
      growth postdischarge. Significant neurodevelopmental impairment was higher in
      infants with the poorest HG from admission to follow-up (adjusted odds ratio
      2.18, 95% confidence interval 1.50-3.15), specifically cognitive and motor
      delays. Infants with poor initial HG and catch-up postdischarge have a lower
      adjusted odds ratio of significant neurodevelopmental impairment (0.35, 95% CI
      0.16-0.74). Infants with poor HG received a longer duration of parenteral
      nutrition and mechanical ventilation and had poor weight gain. CONCLUSIONS: Poor
      HG during the neonatal and postdischarge periods was associated with motor and
      cognitive delays at 16 to 36 months.

PMID- 28759410
TI  - Health Services Use by Late Preterm and Term Infants From Infancy to Adulthood: A
      Meta-analysis.
AB  - CONTEXT: Late-preterm infants born at 34 to 36 weeks' gestation have increased
      risks of various health problems. Health service utilization (HSU) of late
      preterm infants has not been systematically summarized before. OBJECTIVES: To
      summarize the published literature on short- and long-term HSU by late-preterm
      infants versus term infants from infancy to adulthood after initial discharge
      from the hospital. DATA SOURCES: We searched Medline, Embase, the Cumulative
      Index to Nursing and Allied Health Literature, and PsycINFO. STUDY SELECTION:
      Cohort and case-control studies that compared HSU (admissions, emergency
      department visits, etc) between late-preterm infants and term infants were
      included. DATA EXTRACTION: Data extracted included study design, setting,
      population, HSU, covariates, and effect estimates. RESULTS: Fifty-two articles
      were included (50 cohort and 2 case-control studies). Meta-analyses with random
      effect models that used the inverse-variance method found that late-preterm
      infants had higher chances of all-cause admissions than term infants during all
      the time periods. The magnitude of the differences decreased with age from the
      neonatal period through adolescence, with adjusted odds ratios from 2.34 (95%
      confidence intervals 1.19-4.61) to 1.09 (1.05-1.13) and adjusted incidence rate
      ratios from 2.62 (2.52-2.72) to 1.14 (1.11-1.18). Late-preterm infants had higher
      rates of various cause-specific HSU than term infants for jaundice, infection,
      respiratory problems, asthma, and neurologic and/or mental health problems during
      certain periods, including adulthood. LIMITATIONS: Considerable heterogeneity
      existed and was partially explained by the variations in the adjustment for
      multiple births and gestational age ranges of the term infants. CONCLUSIONS: Late
      preterm infants had higher risks for all-cause admissions as well as for various
      cause-specific HSU during the neonatal period through adolescence.

PMID- 28759411
TI  - Controversy About Dialysis for an Adolescent.
AB  - For patients on dialysis, 1 frequent cause of death is their voluntary decision
      to discontinue dialysis. Such decisions raise complex questions when the patient
      is a competent adult. The decisions are even more complex when the patient is an
      adolescent. In this article, we present a case in which a 17-year-old adolescent
      decided that she no longer wished to undergo dialysis through her fistula. Her
      doctors thought that dialysis using any other technique would be too dangerous.
      Four experts in pediatric nephrology, bioethics, and palliative care discuss this
      decision and the different ways that the health care team might respond.

PMID- 28759412
TI  - Endothelial Cell Function and Dysfunction in Critically Ill Children.
AB  - Endothelial cells (ECs) line the lumen of the entire vascular system and actively
      regulate blood flow; maintain blood fluidity; control water, solute, and
      macromolecular transfer between blood and tissue; and modulate circulating immune
      cell recruitment and activation. These vital functions, combined with the broad
      anatomic distribution of ECs, implicate them in all forms of critical illness.
      The present article discusses how ECs adapt and break down during the course of
      critical illness. We first review the biology of ECs, highlighting the vascular
      segmental differences and their specific roles in the maintenance of homeostasis.
      We then discuss how ECs acquire new functions to restore local and systemic
      homeostasis (activation) as well as how breakdowns in EC functions (dysfunction)
      contribute to local and systemic pathologic responses, with clinical
      correlations. Lastly, how these processes have been studied in critically ill
      children is discussed.

PMID- 28759414
TI  - Widespread Hospital Variation in Supplementation of Breastfed Newborns.

PMID- 28759413
TI  - The Yale Observation Scale Score and the Risk of Serious Bacterial Infections in
      Febrile Infants.
AB  - OBJECTIVES: To assess the performance of the Yale Observation Scale (YOS) score
      and unstructured clinician suspicion to identify febrile infants <=60 days of age
      with and without serious bacterial infections (SBIs). METHODS: We performed a
      planned secondary analysis of a prospective cohort of non-critically ill,
      febrile, full-term infants <=60 days of age presenting to 1 of 26 participating
      emergency departments in the Pediatric Emergency Care Applied Research Network.
      We defined SBIs as urinary tract infections, bacteremia, or bacterial meningitis,
      with the latter 2 considered invasive bacterial infections. Emergency department
      clinicians applied the YOS (range: 6-30; normal score: <=10) and estimated the
      risk of SBI using unstructured clinician suspicion (<1%, 1%-5%, 6%-10%, 11%-50%,
      or >50%). RESULTS: Of the 4591 eligible infants, 444 (9.7%) had SBIs and 97
      (2.1%) had invasive bacterial infections. Of the 4058 infants with YOS scores of
      <=10, 388 (9.6%) had SBIs (sensitivity: 51/439 [11.6%]; 95% confidence interval
      [CI]: 8.8%-15.0%; negative predictive value: 3670/4058 [90.4%]; 95% CI: 89.5%
      91.3%) and 72 (1.8%) had invasive bacterial infections (sensitivity 23/95
      [24.2%], 95% CI: 16.0%-34.1%; negative predictive value: 3983/4055 [98.2%], 95%
      CI: 97.8%-98.6%). Of the infants with clinician suspicion of <1%, 106 had SBIs
      (6.4%) and 16 (1.0%) had invasive bacterial infections. CONCLUSIONS: In this
      large prospective cohort of febrile infants <=60 days of age, neither the YOS
      score nor unstructured clinician suspicion reliably identified those with
      invasive bacterial infections. More accurate clinical and laboratory predictors
      are needed to risk stratify febrile infants.

PMID- 28759415
TI  - The Whole "PROOF": Incorporating Evidence-Based Medicine Into Clinical Teaching.

PMID- 28759416
TI  - Observational Assessment in the Febrile Infant.

PMID- 28759417
TI  - Time to Overhaul the "Rule Out Sepsis" Workup.

PMID- 28759418
TI  - Is There a Role for Metformin in the Treatment of Childhood Obesity?

PMID- 28759419
TI  - Alternatives to Appendectomy for Acute Appendicitis.

PMID- 28759420
TI  - Opportunities and Shared Decision-Making to Help Children Who Are Deaf to
      Communicate.

PMID- 28759421
TI  - Children, Gender, Education, and Health.

PMID- 28759422
TI  - Are There Long-term Consequences of Room-Sharing During Infancy?

PMID- 28759423
TI  - Point-Of-Care Ultrasound as an Adjunct in the Diagnosis of Neonatal and Pediatric
      Superficial Soft Tissue Infection: A Report of Two Cases.
AB  - Considerable technological advances, good safety profile, and ease of use have
      converged to support the use of ultrasound (US) as an important adjunct in the
      evaluation of superficial soft tissue infections (SSTI) in general and the
      differential diagnosis of cellulitis and abscess in particular. However, its use
      in neonatal populations has not been described. Pediatric studies report clinical
      examination is not always a reliable method of distinguishing cellulitis from
      abscess. Two (2) case reports are presented to supplement the growing body of
      published data that describe US imaging of SSTIs. In both cases, the US exam
      included the affected area as well as contralateral or adjacent normal skin for
      comparison. Case 1 describes a preterm infant boy who required placement of a
      peripheral intravenous (PIV) line and subsequently developed warm, painful,
      erythematous, and indurated skin in the area of the insertion. Point-of-care US
      (POC-US) was used to diagnose cellulitis, which initiated treatment with
      intravenous antibiotics. Case 2 involves a 7-year-old boy with multiple
      comorbidities who developed a PIV extravasation-related injury that subsequently
      progressed to cellulitis, likely secondary to wound infection with methicillin
      resistant Staphylococcus aureus. Both patients healed completely and without any
      complications. Because treatment of cellulitis is different from that of abscess,
      it is important to obtain real-time data supportive of an accurate diagnosis. In
      these cases, POC-US confirmed the clinical diagnosis of cellulitis and ruled out
      the presence of an abscess.

PMID- 28759424
TI  - Treatment of Thromboangiitis Obliterans Using Smoking Cessation and Far-infrared
      Therapy: A Case Study.
AB  - Thromboangiitis obliterans (Buerger's disease) is a rare, nonatherosclerotic
      segmental inflammatory vasculitis that commonly involves small- and medium-sized
      vessels. Ischemic tenderness impairs patient quality of life and places patients
      at high risk for amputation. The only definitive known treatment is smoking
      cessation. Far-infrared (FIR) therapy has shown promising effects on blood flow
      and healing, but its use in patients with Buerger's disease has not been
      reported. A 31-year-old man with a 15-pack-year history of smoking, no drug
      abuse, and no other significant medical history, trauma, or family history
      diagnosed with thromboangiitis obliterans presented for care at the authors'
      clinic. Claudication with severe tenderness of both legs and an ischemic ulcer
      over the right big toe were noted. After surgical debridement of the devitalized
      tissue, the patient received FIR therapy (5-25 um, peak at 8.2 um) applied 25 cm
      above the surface of the ischemic wound for 40 minutes, 3 times per week. The
      patient also tapered his smoking. The wound started to heal; granulation tissue
      was evident and, after 8 weeks, the right lower extremities gradually rewarmed
      from 24 degrees  C to 28 degrees  C as measured on the dorsal foot. His pain
      level decreased from 8 to 5. FIR therapy was continued until the patient stopped
      smoking (8 months). At the 10-month follow-up visit, the wound had healed
      completely and resting pain had improved. The results of this case study suggest
      additional research to explore the potential effects of FIR on patients with
      thromboangiitis obliterans is warranted.

PMID- 28759425
TI  - Managing Cutaneous Tuberculosis: A Case Report.
AB  - Tuberculosis (TB) continues to be a prevalent disease worldwide; an estimated one
      third of the world's population is infected and 2015 data from the World Health
      Organization show 10 million people had an active infection. Although TB often is
      cited as a disease that most commonly occurs in underdeveloped countries, the
      evolution of drug-resistant forms of TB and infection sensitivity of
      immunocompromised individuals have made this disease a focal point for indus-
      trialized countries as well. When TB is spread, it commonly affects the lungs,
      but it can infect any organ of the body. An uncommon version - cutaneous TB -
      affects < 2% of all individuals with an active form of TB. This study describes a
      34-year-old man with multiple comorbidities, including peripheral vascular
      disease and a remote history of travel to Latin America who presented to a wound
      care clinic with a 2-year history of painful shallow necrotic ulcers on his right
      lower limb and previous treatments that included a positive response to
      antibiotics. Once TB was con rmed via 2 posi- tive Quantiferon Gold tests, the
      patient received therapy (directly observed by the state health department) that
      included pyrazinamide, rifampin, ethambutol, isoniazid, and undocumented vitamin
      B6. Treatment for the TB-related lesions, con- comitant cellulitis, and a Stage 2
      pressure injury under his rst right metatarsal head was initiated as well. The
      patient received local wound care for 40 days that included sharp debridement, of
      oading for the pressure injury, and pain relief before treatment at the wound
      care clinic and daily as prescribed by his primary care provider. All wounds were
      securely covered with collagen dressings followed by silicone-bordered bandages.
      Local wound care was provided for 40 days, with biweekly follow-up for an
      additional 30 days. The wounds resolved and the patient was discharged from the
      wound care clinic but remained on the caseload for 30 days in the event his pain
      increased or the wounds recurred. Cutaneous TB, uncommon and challenging, should
      be a consideration in patients with an increased likelihood of occurrence.

PMID- 28759426
TI  - A Descriptive Study to Assess Quality of Life in Egyptian Patients With a Stoma.
AB  - The creation of a stoma changes bodily appearance and function, which can affect
      quality of life (QOL). A descriptive study using the Short Form 36 (SF-36)
      questionnaire, an instrument that measures 8 physical and mental health concepts,
      was conducted to quantify QOL among patients with a stoma and to interpret how
      stoma creation affects their lives. Participants included a convenience sample of
      persons served by an outpatient surgery clinic in an Egyptian university hospital
      in Cairo between August 2013 and January 2015. Potential participants had to be
      18 years of age or older, have undergone intestinal stoma surgery, live at home,
      be willing to participate, and not be hospitalized or have physical or
      psychological limitations that prevent them from participating in self-care.
      General demographic data and disease characteristics/reasons for stoma creation
      collected included age, gender, and marital status; stoma type, design, and
      duration; and stoma problems/complica- tions. Every patient completed the
      questionnaire individually or, if necessary, with the researcher's assistance;
      the interview took approximately 10 to 15 minutes. Demographic data were
      collected after stoma creation from the patient's medical pro les using a
      predesigned form. The SF-36 scores were linearly converted to a 0 to 100 scale,
      with higher scores indicating bet- ter QOL; scores were considered excellent
      (100), very good (84-99), good (61-83), fair (25-60), and poor (0-24). Data were
      analyzed using descriptive analysis. Independent sample t-tests and 1-way
      analysis of variance tests were used to compare variables, and a 2-tailed
      probability value of 0.05 was used to determine the level of signi cance. Mean
      age of the 96 par- ticipants was 44.12 +/- 12.83 years, and most participants
      were male (58.33%), married (87.5%), and had a permanent stoma (60.42%) with mean
      stoma duration of 2.86 +/- 0.43 years. The majority of patients (68.75%) had a
      colostomy. All patients (100%) reported 1 or more problems related to their
      stoma, including nding privacy to empty the pouch (51), problems with leakage
      (37), the need to adapt their clothing (69), local skin irritation (28), the
      presence of offensive odor and/or bowel noise (90), and dif culties participating
      in social activities (72). Most of the QOL subscales were in the fair QOL
      category range (between 49.55 +/- 31.59 and 59.54 +/- 30). Compared to persons
      with a temporary stoma, participants with a permanent stoma had signi cantly
      higher physical role function scores (38.76 +/- 33.30 versus 70.92 +/- 35.59; P
      %lt;.05). Patients with a stoma constructed due to trauma had higher general
      health scale scores than persons with a stoma constructed due to in ammatory
      bowel disease or colon cancer (mean [SD] 61.6 +/- 31.75, 57.14 +/- 26.26, and
      46.55 +/- 30.85, respectively; P <.05). Ostomy-speci c QOL studies are needed to
      increase understanding about the needs of stoma patients in Egypt; the results of
      this study suggest their QOL is not good and improvements in proper perioperative
      counseling and specialized nursing care may be needed.

PMID- 28759427
TI  - Negative Pressure Wound Therapy for Patients With Complex Abdominal Wounds.
AB  - : The combination of open abdominal wounds and intra-abdominal infections is
      challenging to treat and often results in critical illness associated with high
      mortality. OBJECTIVE: The aim of this study is to evaluate the feasibility of
      using negative pressure wound therapy (NPWT) to manage complex abdominal wounds
      and summarize relevant treatment experiences. MATERIALS AND METHODS: A
      retrospective analysis of records from April 2012 to May 2015 identified 13
      hospitalized patients with open abdominal wounds complicated by intra-abdominal
      infections. Patients received systemic antibiotics. Negative pressure wound
      therapy was applied at the bedside if prior debridement or decompression and
      drainage via laparotomy did not yield positive results or if the patient could
      not undergo surgery. RESULTS: Of the 13 patients who were included in the study,
      10 achieved wound closure (range, 19-52 days; median, 26 days). Among the 3
      patients who did not achieve closure, 1 requested transfer to a hospital in his
      hometown, 1 developed an intestinal stula that required surgery, and 1 died of a
      digestive tract hemorrhage unrelated to NPWT. CONCLUSIONS: By providing suf cient
      drainage, NPWT effectively removed wound fluid and infectious material. The
      reduced edema helped lower intra-abdominal pressure, reduce the risk of abdominal
      compartment syndrome and infection, and improve patient prognosis.

PMID- 28759428
TI  - Negative Pressure Wound Therapy for Patients With Complex Abdominal Wounds.
AB  - BACKGROUND: Research on treatment alternatives that improve wound healing is an
      ever-evolving area in medicine, and a wound healing agent that carries minimal
      pain, discomfort, and scarring for patients with burn wounds, venous and
      decubitis ulcers, traumatic wounds, and many others is needed. The phases of
      wound healing include homeostasis, inflammation, migration, proliferation, and
      maturation. Adeps suillus (axonge) is known as a therapeutic agent for skin
      diseases and mainly consists of triglycerides. OBJECTIVE: In the current study,
      the proliferation effect of axonge was determined on human normal epidermal
      keratinocyte (HaCaT) cells and human normal foreskin fibroblast cell line (BJ)
      cells. MATERIALS AND METHODS: Experimental steps included preparation of HaCaT
      and BJ cell lines, axonge's stable tetrazolium salt-based proliferation assay,
      and evaluation of the wound healing effect of axonge on HaCaT and BJ cells.
      RESULTS: Axonge concentrations of 3.12 ug/mL, 6.25 ug/mL, 12.5 ug/mL, 25 ug/mL,
      and 50 ug/mL showed no cytotoxic effect on both HaCaT and BJ cells for 24, 48,
      and 72 hours. Considering the wound area of HaCaT cells, after 6 hours the wound
      healing effect of the axonge group reached almost 70% and then stopped. According
      to the results of the study on BJ cells, after 6 hours axonge wound closure was
      found to be 50% while the control group was only 10%. CONCLUSION: On the basis of
      this study, the authors determined that axonge might have potential for use in
      wound healing.

PMID- 28759429
TI  - Serial Surgical Debridement of Common Pressure Injuries in the Nursing Home
      Setting: Outcomes and Findings.
AB  - OBJECTIVE: This study examined the efficacy of bedside surgical debridement in a
      nursing home population. MATERIALS AND METHODS: A retrospective chart review was
      performed of sacrum, sacrococcyx, coccyx, ischium, and trochanter (SSCIT) region
      pressure injuries in the Skilled Wound Care practice (Los Angeles, CA). The
      patient population was refined from 2128 to 227 patients visited 8 or more times
      during nursing home stays found to have 1 or more SSCIT pressure injuries. Of the
      227 patients, there were approximately 319 individual SSCIT wounds, with an
      average of 1.4 SSCIT wounds per patient. Bedside surgical debridement was
      performed using a sharp excisional technique on 190 of 319 (59.5%) SSCIT wounds.
      RESULTS: An analysis of the square surface area of the 190 debrided wound sites
      revealed a mean ulcer surface area of 20.76 cm2. Of those 190 wound sites, 138
      (73%) had a reduction in square surface area, and 52 (27%) had no change or an
      increase in square surface area and were categorized as nonresponders. Of the
      wounds that did improve by a reduction in wound surface area, the average wound
      surface area reduction was 6.81 cm2 at 4 weeks (25%), 8.91 cm2 reduction at 8
      weeks (33%), and 10.87 cm2 reduction at 12 weeks (40%). From the 190 wound sites,
      there were a total of 43 (23%) wounds that had a square surface area of 0
      (reepithelialized), which has a healing rate of 23%. CONCLUSION: Traditional
      bedside debridement provides excellent results in reducing the square surface
      area for a majority of wounds. Whether used alone or as an adjunct to any
      treatment plan, the use of surgical sharp equipment aids in achieving good wound
      healing and advancing the rate of wound closure. Although wound healing requires
      many components, sharp debridement can effectively remove devitalized tissue and
      is a proven significant component to advancing wound closure.

PMID- 28759430
TI  - Squamous Cell Carcinoma Arising in a Chronic, Nonhealing Diabetic Foot Ulcer.
AB  - : Diabetic foot ulcers (DFUs) are a severe and costly complication of diabetes
      and may result in foot amputation. CASE REPORT: A 69-year-old man with a 10-year
      history of type 2 diabetes, who was undergoing routine care for diabetes in the
      authors' clinic, developed a DFU of his right foot of 4 years' duration. The
      wound did not respond to conventional treatments, and imaging studies were
      normal. His 2 biopsies tested negative for malignancy. The DFU was fully removed
      surgically. Following surgical removal, squamous cell carcinoma (SCC) was
      diagnosed in the histologic study of the wound. CONCLUSION: Clinicians should
      consider a diagnosis of SCC in any chronic, nonhealing DFU. Early surgical
      resection of a chronic, nonhealing DFU may prevent development of SCC in an
      ulcer.

PMID- 28759431
TI  - Venous Ulcers Treated With a Hyaluronic Acid Extracellular Matrix and Compression
      Therapy: Interim Analysis of a Randomized Controlled Trial.
AB  - : Diabetic foot ulcers (DFUs) are a severe and costly complication of diabetes
      and may result in foot amputation. CASE REPORT: A 69-year-old man with a 10-year
      history of type 2 diabetes, who was undergoing routine care for diabetes in the
      authors' clinic, developed a DFU of his right foot of 4 years' duration. The
      wound did not respond to conventional treatments, and imaging studies were
      normal. His 2 biopsies tested negative for malignancy. The DFU was fully removed
      surgically. Following surgical removal, squamous cell carcinoma (SCC) was
      diagnosed in the histologic study of the wound. CONCLUSION: Clinicians should
      consider a diagnosis of SCC in any chronic, nonhealing DFU. Early surgical
      resection of a chronic, nonhealing DFU may prevent development of SCC in an
      ulcer.

PMID- 28759432
TI  - Medical education in Myanmar: a critical commentary.

PMID- 28759433
TI  - Engineering-derived approaches for iPSC preparation, expansion, differentiation
      and applications.
AB  - Remarkable achievements have been made since induced pluripotent stem cells
      (iPSCs) were first introduced in 2006. Compared with non-pluripotent stem cells,
      iPSC research faces several additional complexities, such as the choice of
      extracellular matrix proteins, growth and differentiation factors, as well as
      technical challenges related to self-renewal and directed differentiation.
      Overcoming these challenges requires the integration of knowledge and
      technologies from multiple fields including cell biology, biomaterial science,
      engineering, physics and medicine. Here, engineering-derived iPSC approaches are
      reviewed according to three aspects of iPSC studies: preparation, expansion,
      differentiation and applications. Engineering strategies, such as 3D systems
      establishment, cell-matrix mechanics and the regulation of biophysical and
      biochemical cues, together with engineering techniques, such as 3D scaffolds,
      cell microspheres and bioreactors, have been applied to iPSC studies and have
      generated insightful results and even mini-organs such as retinas, livers and
      intestines. Specific results are given to demonstrate how these approaches impact
      iPSC behavior, and related mechanisms are discussed. In addition, cell printing
      technologies are presented as an advanced engineering-derived approach since they
      have been applied in both iPSC studies and the construction of diverse tissues
      and organs. Further development and possible innovations of cell printing
      technologies are presented in terms of creating complex and functional iPSC
      derived living tissues and organs.

PMID- 28759434
TI  - Development of hydrophilic GO-ZnO/PES membranes for treatment of pharmaceutical
      wastewater.
AB  - Membrane application in water reclamation is challenged by fouling which
      deteriorates membrane performance in terms of permeate flux and solute rejection.
      Several studies focusing on antifouling membranes incorporated with nanoparticles
      have been carried out, but these membranes are not yet a viable solution due to
      their high energy requirements and inability to completely remove or degrade
      trace organic compounds (TOrCs). Therefore, this study aims at fabricating
      polyethersulfone (PES) membranes for treatment of pharmaceutical wastewater by
      using a unique membrane synthesis approach. PES membranes were synthesised by
      casting two different solutions before coagulation. Therefore, the synthesis
      technique was called 'double-casting phase inversion'. The membranes were
      impregnated with nanohybrid graphene oxide-zinc oxide (GO-ZnO) to increase their
      hydrophilicity, rejection of pharmaceuticals (by decreasing membrane-solute
      hydrophobic interactions), resistance to organic fouling and photodegradation
      properties. The addition of GO-ZnO increased membrane hydrophilicity and pure
      water permeability. The rejection of TOrCs and anti-fouling properties were also
      improved due to a reduction in membrane-solute and membrane-foulant hydrophobic
      interactions, respectively. In addition to improved TOrC rejection properties and
      resistance to fouling, GO-ZnO/PES membranes degraded Brilliant Black.

PMID- 28759435
TI  - Response surface modeling of boron adsorption from aqueous solution by
      vermiculite using different adsorption agents: Box-Behnken experimental design.
AB  - In this study, a different method was applied for boron removal by using
      vermiculite as the adsorbent. Vermiculite, which was used in the experiments, was
      not modified with adsorption agents before boron adsorption using a separate
      process. Hexadecyltrimethylammonium bromide (HDTMA) and Gallic acid (GA) were
      used as adsorption agents for vermiculite by maintaining the solid/liquid ratio
      at 12.5 g/L. HDTMA/GA concentration, contact time, pH, initial boron
      concentration, inert electrolyte and temperature effects on boron adsorption were
      analyzed. A three-factor, three-level Box-Behnken design model combined with
      response surface method (RSM) was employed to examine and optimize process
      variables for boron adsorption from aqueous solution by vermiculite using HDTMA
      and GA. Solution pH (2-12), temperature (25-60  degrees C) and initial boron
      concentration (50-8,000 mg/L) were chosen as independent variables and coded x1,
      x2 and x3 at three levels (-1, 0 and 1). Analysis of variance was used to test
      the significance of variables and their interactions with 95% confidence limit
      (alpha = 0.05). According to the regression coefficients, a second-order
      empirical equation was evaluated between the adsorption capacity (qi) and the
      coded variables tested (xi). Optimum values of the variables were also evaluated
      for maximum boron adsorption by vermiculite-HDTMA (HDTMA-Verm) and vermiculite-GA
      (GA-Verm).

PMID- 28759436
TI  - Elevational characteristics of the archaeal community in full-scale activated
      sludge wastewater treatment plants at a 3,660-meter elevational scale.
AB  - Due to the important roles of archaea in wastewater treatment processes, archaeal
      communities have been studied extensively in various anaerobic reactors, but the
      knowledge of archaeal communities in full-scale activated sludge wastewater
      treatment plants (WWTPs) remains quite poor. In this study, 454-pyrosequencing
      was for the first time employed to investigate archaeal communities from 20 full
      scale activated sludge WWTPs distributed at a 3,660-meter elevational scale in
      China. Results showed that archaeal communities from WWTPs were dominated by
      Methanosarcinales (84.6%). A core archaeal population (94.5%) composed of
      Methanosaeta, Methanosarcina, Methanogenium and Methanobrevibacter was shared
      among WWTPs. The elevational pattern of archaeal communities was observed in
      WWTPs, with an elevational threshold associated with archaeal community richness
      and structures at approximately 1,500 meters above sea level (masl). A declining
      trend in community richness with increasing elevation was observed at higher
      elevations, whereas no trend was presented at lower elevations. Spearman
      correlation analysis indicated that the archaeal community richness at higher
      elevations was associated with more environmental variables than that at lower
      elevations. Redundancy analysis indicated that wastewater variables were the
      dominant contributors to the variation of community structures at higher
      elevations, followed by operational variables and elevation.

PMID- 28759437
TI  - Modified ADM1 for high-rate anaerobic co-digestion of thermally pre-treated
      brewery surplus yeast wastewater.
AB  - Co-digestion of surplus yeast with brewery wastewater is a potentially economical
      method for recovering energy, in the form of biogas, from this difficult to
      dispose of by-product. In this work a modified version of the ADM1 (Anaerobic
      Digestion Model No. 1) was calibrated for an anaerobic digester fed with
      thermally pre-treated brewery yeast surplus wastewater. The model could predict
      changes to reactor methane production and reduction of biodegradable matter when
      fed with both pre-treated and untreated yeast surplus wastewater at varying
      loading rates. Model calibration focused on low temperature thermal pre-treatment
      as experiments into a combined thermal-alkaline pre-treatment did not show any
      significant improvements. A low temperature pre-treatment of 60  degrees C for 30
      minutes was sufficient for yeast inactivation and allowed for stable and more
      efficient operation of the high-rate anaerobic digester over a period of 232
      days. The low temperature and time for pre-treatment also reduced the evaporation
      of easily biodegradable residual ethanol present in the influent, while still
      maintaining a low level of suspended matter. Inline measurements of gas
      composition, production and effluent chemical oxygen demand were sufficient for
      reliable model calibration of these same outputs. More detailed characterization
      of influent and effluent is required if organic acid concentrations for pH
      control are needed.

PMID- 28759438
TI  - Influence of surface modification by sulfuric acid on coking coal's adsorption of
      coking wastewater.
AB  - Coking coal, the raw material of a coke plant, was applied to the adsorption of
      coking wastewater. In this study, coking coal was directly treated with sulfuric
      acid to improve its surface properties and adsorption ability. Acid treatment was
      carried out at various concentrations, by varying from 0.001 to 1 mol/L. The
      samples were characterized by ash content analysis, scanning electron microscope
      (SEM), N2 adsorption-desorption analysis, Fourier transform infrared spectroscopy
      (FTIR), X-ray photoelectron spectroscopy (XPS), wettability analysis, and zeta
      potential analysis. These results demonstrated that H+ could react with inorganic
      minerals, which resulted in a significant variation of the chemical composition
      and the structure of coal surface. Furthermore, both the ash content and the
      surface content of O = C-O, C = O and C-O groups declined gradually as the
      concentration of sulfuric acid increased, while the surface area and pore volume
      of micropore, the lipophilic and hydrophobic properties, and zeta potential
      magnitude increased, resulting in enhanced hydrophobic and Van der Waals' forces
      between the fine coal and organic pollutants. Characterization modification
      showed a better performance in adsorption, the removal rate enhanced from 23% to
      42% after treated by 1 mol/L sulfuric acid. It was concluded that the acid
      activation modified the lipophilic and hydrophobic properties, the surface charge
      properties, surface area and pore volume, the content of oxygen functional
      groups, all of which could be potentially useful in wastewater adsorption.

PMID- 28759439
TI  - Degradation kinetics of organic dyes in water by high voltage atmospheric air and
      modified air cold plasma.
AB  - High voltage atmospheric cold plasma (HVACP) is a novel, non-thermal technology
      which has shown potential for degradation of various toxic components in
      wastewater. In this study, HVACP was used to examine the degradation kinetics of
      methyl red, crystal violet and fast green FCF dyes. HVACP discharge was found to
      be a source of reactive nitrogen and oxygen species. High voltage application
      completely degraded all dyes tested in less than 5 min treatment time. Plasma
      from modified gas (~65% O2) further reduced the treatment time by 50% vs. plasma
      from dry air. First order and Weibull models were fitted to the degradation data.
      The Weibull model was found better in explaining the degradation kinetics of all
      the treated dyes.

PMID- 28759440
TI  - Removal of calcium and magnesium ions from shale gas flowback water by chemically
      activated zeolite.
AB  - Shale gas has become a new sweet spot of global oil and gas exploration, and the
      large amount of flowback water produced during shale gas extraction is attracting
      increased attention. Internal recycling of flowback water for future hydraulic
      fracturing is currently the most effective, and it is necessary to decrease the
      content of divalent cations for eliminating scaling and maintaining effectiveness
      of friction reducer. Zeolite has been widely used as a sorbent to remove cations
      from wastewater. This work was carried out to investigate the effects of zeolite
      type, zeolite form, activation chemical, activation condition, and sorption
      condition on removal of Ca2+ and Mg2+ from shale gas flowback water. Results
      showed that low removal of Ca2+ and Mg2+ was found for raw zeolite 4A and zeolite
      13X, and the efficiency of the mixture of both zeolites was slightly higher.
      Compared with the raw zeolites, the zeolites after activation using NaOH and NaCl
      greatly improved the sorption performance, and there was no significant
      difference between dynamic activation and static activation. Dynamic sorption
      outperformed static sorption, the difference exceeding 40% and 7-70% for removal
      of Ca2+ and Mg2+, respectively. Moreover, powdered zeolites outperformed
      granulated zeolites in divalent cation removal.

PMID- 28759441
TI  - Impact of steel slag on the ammonium adsorption by zeolite and a new
      configuration of zeolite-steel slag substrate for constructed wetlands.
AB  - The CaO dissolution from slag, as well as the effects of influencing parameters
      (i.e. pH and Ca2+ concentration) on the ammonium adsorption onto zeolite, was
      systematically studied in this paper. Modeling results of Ca2+ and OH- release
      from slag indicated that pseudo-second-order reaction had a better fitness than
      pseudo-first-order reaction. Changing pH value from 7 to 12 resulted in a drastic
      reduction of the ammonium adsorption capacity on zeolite, from the peak
      adsorption capacity at pH 7. High Ca2+ concentration in solution also inhibited
      the adsorption of ammonium onto zeolite. There are two proposed mechanisms for
      steel slag inhibiting the ammonium adsorption capacity of zeolite. On the one
      hand, OH- released from steel slag can react with ammonium ions to produce the
      molecular form of ammonia (NH3.H2O), which would cause the dissociation of NH4+
      from zeolite. On the other hand, Ca2+ could replace the NH4+ ions to adhere onto
      the surface of zeolite. An innovative substrate filling configuration with
      zeolite placed upstream of the steel slag was then proposed to eliminate the
      disadvantageous effects of steel slag. Experimental results showed that this
      novel filling configuration was superior to two other filling configurations in
      terms of ammonium removal.

PMID- 28759442
TI  - A comprehensive evaluation of regional water safety systems based on a similarity
      cloud model.
AB  - Regional water safety systems are affected by social, economic, ecological,
      hydrological and other factors, and their effects are complicated and variable.
      Studying water safety systems is crucial to promoting the coordinated development
      of regional water safety systems and anthropogenic processes. Thus, a similarity
      cloud model is developed to simulate the evolution mechanisms of fuzzy and
      complex regional systems of water security and overcome the uncertainty that is
      associated with the indices that are used in water safety index systems. This
      cloud generator is used to reciprocally transform a qualitative cloud image with
      a quantitative cloud characteristic value, and the stochastic weight assignment
      method is used to determine the weight of the evaluation indices. The results of
      case studies show that Jiansanjiang's water safety systems were in a safe state
      in 2002-2011, but the water safety systems in the arid area of Yinchuan City were
      in a dangerous state in 2006-2007 because of climate factors and a lack of
      effective water and soil resource protection. The experimental results are
      consistent with the research subjects' actual situations, and the proposed model
      provides a tool for decision makers to better understand the security issues that
      are associated with regional water safety systems.

PMID- 28759443
TI  - Recycling of end-of-life reverse osmosis membranes by oxidative treatment: a
      technical evaluation.
AB  - The adverse impacts caused by the disposal of thousands of tonnes per annum of
      reverse osmosis (RO) membranes modules have grown dramatically around the world.
      The objective of this study was to evaluate the technical feasibility of
      recycling by chemical oxidation of end-of-life RO membranes for applications in
      other separation processes with specifications less rigorous. The recycling
      technique consisted in to cause a membrane exposition with oxidant solutions in
      order to remove its aromatic polyamide layer and subsequent conversion to a
      porous membrane. The recycling technique was evaluated by water permeability and
      salt rejection tests before and after the oxidative treatments. Initially,
      membranes' chemical cleaning and pretreatment procedures were assessed. Among
      factors evaluated, the oxidizing agent, its concentration and pH, associated with
      the oxidative treatment time, showed important influence on the oxidation of the
      membranes. Results showed that sodium hypochlorite and potassium permanganate are
      efficient agents for the membrane recycling. The great increased permeability and
      decreased salt rejection indicated changes on membranes' selective properties.
      Scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX),
      atomic force microscopy (AFM), and contact angle characterization techniques
      revealed marked changes on the main membranes' physical-chemical properties, such
      as morphology, roughness and hydrophobicity. Reuse of produced effluents and
      fouling tendency of recycled membranes were also evaluated.

PMID- 28759444
TI  - Tailing propensity in the ultraviolet disinfection of trickling filter and
      activated sludge wastewater treatment processes.
AB  - In this paper, the effect of suspended flocs on the tailing of ultraviolet (UV)
      disinfection kinetics of secondary effluents was examined. To achieve this goal,
      final effluents produced in two processes for treating wastewater; namely, a
      trickling filter system and an activated sludge system, were collected and their
      UV disinfection were compared. Tailing of the UV dose response curve was
      controlled by the fraction of flocs that are both culturable and UV-resistant,
      referred to as the 'tailing propensity'. Using this parameter, the contribution
      of various floc size fractions in reducing the UV disinfection efficiency of
      wastewater samples was quantified. Activated sludge flocs larger than 125 MUm
      exhibited as much as 35 times greater tailing propensity than smaller flocs in
      the range of 20-25 MUm. Within a fixed size range, the tailing propensity of
      flocs generated in the trickling filter system was 3 to 8 times higher than that
      of activated sludge flocs, and this difference increased with the floc size. A
      mathematical model was developed to predict the UV disinfection of secondary
      effluents from suspended particle size distribution data. The model showed good
      agreement with experimental results.

PMID- 28759445
TI  - Estimation of water quality by UV/Vis spectrometry in the framework of treated
      wastewater reuse.
AB  - The aim of this study is to investigate the potential of ultraviolet/visible
      (UV/Vis) spectrometry as a complementary method for routine monitoring of
      reclaimed water production. Robustness of the models and compliance of their
      sensitivity with current quality limits are investigated. The following
      indicators are studied: total suspended solids (TSS), turbidity, chemical oxygen
      demand (COD) and nitrate. Partial least squares regression (PLSR) is used to find
      linear correlations between absorbances and indicators of interest. Artificial
      samples are made by simulating a sludge leak on the wastewater treatment plant
      and added to the original dataset, then divided into calibration and prediction
      datasets. The models are built on the calibration set, and then tested on the
      prediction set. The best models are developed with: PLSR for COD (Rpred2 = 0.80),
      TSS (Rpred2 = 0.86) and turbidity (Rpred2 = 0.96), and with a simple linear
      regression from absorbance at 208 nm (Rpred2 = 0.95) for nitrate concentration.
      The input of artificial data significantly enhances the robustness of the models.
      The sensitivity of the UV/Vis spectrometry monitoring system developed is
      compatible with quality requirements of reclaimed water production processes.

PMID- 28759446
TI  - Numerical modelling of air-water flows in sewer drops.
AB  - The presence of dissolved oxygen (DO) in water flows is an important factor to
      ensure the aerobic conditions recognised as beneficial to preventing the
      occurrence of detrimental effects. The incorporation of DO in wastewater flowing
      in sewer systems is a process widely investigated in order to quantify the effect
      of continuous reaeration through the air-liquid interface or air entrained due to
      the presence of singularities such as drops or junctions. The location of sewer
      drops to enhance air entrainment and subsequently reaeration is an effective
      practice to promote aerobic conditions in sewers. In the present paper, vertical
      drops, backdrops and stepped drops were modelled using the computational fluid
      dynamics (CFD) code FLOW-3D(r) to evaluate the air-water flows due to the
      turbulence induced by the presence of these types of structures. An assessment of
      the hydraulic variables and an analysis of the air entrainment based on the
      available experimental studies were carried out. The results of the CFD models
      for these structures were validated using measurements of discharge, pressure
      head and water depth obtained in the corresponding physical models. A very good
      fit was obtained for the hydraulic behaviour. After validation of numerical
      models, analysis of the air entrainment was carried out.

PMID- 28759447
TI  - Membrane fouling reduction in a cost-effective integrated system of microbial
      fuel cell and membrane bioreactor.
AB  - Microbial fuel cells (MFC) and membrane bioreactors (MBR) are promising
      technologies for wastewater treatment. However, both of them have some drawbacks
      and application limitations. A cost-effective hybrid system (EMBR) integrating
      MFC with MBR was evaluated in terms of treatment performance and membrane
      fouling. In this paper, two electric field directions with a membrane module in
      the middle were applied to explore the mechanism of membrane fouling mitigation
      in EMBRs. In both configurations of EMBRs, microbial activity and degradation
      ability of activated sludge for chemical oxygen demand and NH4+-N removals could
      be enhanced compared with those for the controlled MBR. In addition, the
      irreversible resistance significantly decreased, especially in the EMBR(-) with a
      longer operation time. Furthermore, two critical factors, namely enhanced
      bioflocculation and electrophoresis forces, were compared based on key parameters
      (zeta potential, particle size distribution and extracellular polymeric
      substances). The electrophoresis forces made a greater contribution to fouling
      alleviation than that conducted by the enhanced bioflocculation. The results
      suggested that EMBR, as a promising wastewater treatment technology, improved
      effluent quality and reduced energy consumption.

PMID- 28759448
TI  - A novel electro-catalytic degradation method of phenol wastewater with Ti/IrO2
      Ta2O5 anodes in high-gravity fields.
AB  - In the electro-catalytic degradation process of phenol wastewater, bubbles and
      mass transfer limitation will result in the decrease in wastewater degradation
      efficiency, a long electrolysis time and a high energy consumption. Self-made
      Ti/IrO2-Ta2O5 anodes and a high-gravity electro-catalytic reactor were used to
      improve them. The Ti/IrO2-Ta2O5 anode was prepared with a thermal decomposition
      method and characterized by scanning electron microscopy (SEM). Under optimum
      conditions, the removal efficiencies of phenol, total organic carbon (TOC) and
      chemical oxygen demand (COD) respectively reached 94.77%, 50.96% and 41.2% after
      2 h electrolysis in the high-gravity field, which were respectively 10.93%,
      16.72% and 24.84% higher than those in the normal gravity field. For about the
      same removal efficiencies, the electrolysis time and energy consumed in the high
      gravity field were 33.3% and 15.4% lower than those consumed in the normal
      gravity field, respectively. The degradation pathway of phenol detected by high
      performance liquid chromatography (HPLC) was unchanged in the high-gravity field,
      but the degradation rate of phenol increased. The Ti/IrO2-Ta2O5 anode provided
      good stability because the removal efficiencies of phenol and TOC decreased
      slightly and the surface morphology of the coating was almost unchanged when it
      had been used in electrolysis for 11 months, about 1,200 h, in the high-gravity
      field. Results indicated that the phenol wastewater degradation efficiency was
      improved, the time was shortened, and the energy consumption was reduced in the
      high-gravity field.

PMID- 28759449
TI  - Adsorption of Hg(II) and Pb(II) ions by nanoscale zero valent iron supported on
      ostrich bone ash in a fixed-bed column system.
AB  - In this research, ostrich bone ash (OBA) was modified with nanoscale zerovalent
      iron (nZVI) particles and applied as a novel composite adsorbent (OBA/nZVI) for
      dynamic adsorption/reduction of Hg(II) and Pb(II) ions in a fixed-bed column
      system. Entrapment of nZVI in OBA beads barricades the particles from oxidation
      and aggregation. The dynamic behavior of metal ions removal by OBA/nZVI was
      assessed as a function of inlet flow rates, bed height, initial pollutants
      concentration and pH. The synthesized OBA/nZVI composite was characterized by
      several physicochemical techniques. Increase in pH and bed height and decrease in
      flow rates and initial metal concentration resulted in delay of breakthrough
      time. OBA breakthrough profile is sharper than the OBA/nZVI breakthrough curve
      for both metal ions and the breakthrough times increase in the order OBA/nZVI
      Hg(II) > OBA/nZVI-Pb(II) > OBA-Pb(II) > OBA-Hg(II). Based on the experiment
      results, redox reaction is expected to occur to a certain extent, as the standard
      reduction potentials of Hg(II) and Pb(II) are more than that of Fe(II). From a
      practical point of view, the OBA/nZVI could be applied as a material to remove
      Hg(II) and Pb(II) ions from natural surface and ground water with a pH value of 5
      9.

PMID- 28759450
TI  - Performance of air-cathode stacked microbial fuel cells systems for wastewater
      treatment and electricity production.
AB  - Two different air-cathode stacked microbial fuel cell (MFC) configurations were
      evaluated under continuous flow during the treatment of municipal wastewater and
      electricity production at a hydraulic retention time (HRT) of 3, 1, and 0.5 d.
      Stacked MFC 1 was formed by 20 individual air-cathode MFC units. The second
      stacked MFC (stacked MFC 2) consisted of 40 air-cathode MFC units placed in a
      shared reactor. The maximum voltages produced at closed circuit (1,000 Omega)
      were 170 mV for stacked MFC 1 and 94 mV for stacked MFC 2. Different power
      densities in each MFC unit were obtained due to a potential drop phenomenon and
      to a change in chemical oxygen demand (COD) concentrations inside reactors. The
      maximum power densities from individual MFC units were up to 1,107 mW/m2 for
      stacked MFC 1 and up to 472 mW/m2 for stacked MFC 2. The maximum power densities
      in stacked MFC 1 and MFC 2 connected in series were 79 mW/m2 and 4 mW/m2,
      respectively. Electricity generation and COD removal efficiencies were reduced
      when the HRT was decreased. High removal efficiencies of 84% of COD, 47% of total
      nitrogen, and 30% of total phosphorus were obtained during municipal wastewater
      treatment.

PMID- 28759451
TI  - Flocculating and dewatering performance of hydrophobic and hydrophilic solids
      using a thermal-sensitive copolymer.
AB  - Thermal-sensitive polymers have been tested on settling, compacting or dewatering
      of clays or oil sand tailings. However, not much attention has been paid to
      explore the effect of temperature on flocculating performance using thermal
      sensitive polymers. In this study, poly(NIPAM-co-DMAPMA) was synthesized and
      employed to investigate the flocculating and re-flocculating performance of
      hydrophilic and hydrophobic particles at two specific temperatures; meanwhile
      settling and dewatering behaviors were also investigated. The results
      demonstrated that good flocculating performances were achieved at both room
      temperature (~23  degrees C) and lower critical solution temperature (45  degrees
      C). Furthermore, larger flocs were formed at 45  degrees C as the copolymer was
      added. Floc strength and re-flocculating ability of the flocs were also
      intensified prominently at 45  degrees C. Additionally, settling and dewatering
      rates of suspensions were improved, and the moisture of filtered cakes was
      reduced when suspensions were at 45  degrees C. The phenomena could be justified
      by the phase transition of the copolymer from hydrophilicity to hydrophobicity as
      the temperature increased. There were much stronger adhesion forces between
      particles and higher adsorption amount of the copolymer onto solid surfaces at 45
      degrees C. Therefore, the copolymer may be promising in solid-liquid separation
      to improve the floc size, floc strength, and settling and dewatering rate to
      achieve much lower moisture filtered cake.

PMID- 28759452
TI  - Influence of nanoparticles on filterability of fruit-juice industry wastewater
      using submerged membrane bioreactor.
AB  - In this study, polyethersulfone (PES) ultrafiltration membrane surface was
      modified with nano-sized zinc oxide (nZnO) and silver (nAg) to improve the
      membrane filterability of the mixed liquor and used to treat fruit-juice industry
      wastewater in a submerged membrane bioreactor (MBR). The nAg was synthesized
      using three different methods. In the first method, named as nAg-M1, PES membrane
      was placed on the membrane module and nAg solution was passed through the
      membrane for 24 h at 25 +/- 1  degrees C. In the second method, named as nAg-M2,
      PES membrane was placed in a glass container and it was shaken for 24 h at 150
      rpm at 25 +/- 1  degrees C. In the third method, named as nAg-M3, Ag
      nanoparticles were loaded onto PES membrane in L-ascorbic acid solution (0.1
      mol/L) at pH 2 for 24 h at 150 rpm at 25 +/- 1  degrees C. For the preparation of
      nZnO coated membrane, nZnO nanoparticles solution was passed through the membrane
      for 24 h at 25 +/- 1  degrees C. Anti-fouling performance of pristine and coated
      membranes was examined using the submerged MBR. The results showed that nZnO and
      nAg-M3 membranes showed lower flux decline compared with pristine membrane.
      Moreover, pristine and coated PES membranes were characterized using a permeation
      test, contact angle goniometer, and scanning electron microscopy.

PMID- 28759453
TI  - Preventing maritime transport of pathogens: the remarkable antimicrobial
      properties of silver-supported catalysts for ship ballast water disinfection.
AB  - Ship ballast water (SBW) antimicrobial treatment is considered as a priority
      issue for the shipping industry. The present work investigates the possibility of
      utilizing antimicrobial catalysis as an effective method for the treatment of
      SBW. Taking into account the well-known antimicrobial properties of ionic silver
      (Ag+), five silver-supported catalysts (Ag/gamma-Al2O3) with various loadings
      (0.05, 0.1, 0.2, 0.5, and 1 wt%) were prepared and examined for the antimicrobial
      treatment of SBW. The bactericidal activity of the aforementioned catalysts was
      investigated towards the inhibition of Escherichia coli (Gram-negative) and
      Escherichia faecalis (Gram-positive) bacteria. Catalytic experiments were
      conducted in a three-phase continuous flow stirred tank reactor, used in a semi
      batch mode. It was found that using the catalyst with the lowest metal loading,
      the inhibition of E. coli reached 95.8% after 30 minutes of treatment of an E.
      coli bacterial solution, while the inhibition obtained for E. faecalis was 76.2%
      after 60 minutes of treatment of an E. faecalis bacterial solution. Even better
      results (100% inhibition after 5 min of reaction) were obtained using the
      catalysts with higher Ag loadings. The results of the present work indicate that
      the prepared monometallic catalysts exert their antimicrobial activity within a
      short period of time, revealing, for the first time ever, that the field of
      antimicrobial heterogeneous catalysis using deposited ionic silver on a solid
      support may prove decisive for the disinfection of SBW.

PMID- 28759454
TI  - Assessing biodiesel quality parameters for wastewater grown Chlorella sp.
AB  - Microalgae are reported as the efficient source of renewable biodiesel which
      should be able to meet the global demand of transport fuels. Present study is
      focused on assessment of wastewater grown indigenous microalga Chlorella sp. for
      fuel quality parameters. This was successfully grown in secondary treated waste
      water diluted with tap water (25% dilution) in glass house. The microalga showed
      a dry weight of 0.849 g L-1 with lipid content of 27.1% on dry weight basis on
      21st day of incubation. After transesterification, the yield of fatty acid methyl
      ester was 80.64% with major fatty acids as palmitic, linoleic, oleic and
      linolenic. The physical parameters predicted from empirical equations in the
      biodiesel showed cetane number as 56.5, iodine value of 75.5 g I2 100 g-1, high
      heating value 40.1 MJ kg-1, flash point 135  degrees C, kinematic viscosity 4.05
      mm2 s-1 with density of 0.86 g cm3 and cold filter plugging point as 0.7  degrees
      C. Fourier transform infra-red (FTIR), 1H, 13C NMR spectrum confirmed the
      chemical nature of biodiesel. The results indicated that the quality of biodiesel
      was almost as per the criterion of ASTM standards; hence, wastewater grown
      Chlorella sp. can be used as a promising strain for biodiesel production.

PMID- 28759455
TI  - Decomposition of the organic matter of natural and concentrated vinasse in sandy
      and clayey soils.
AB  - Vinasse has been used as fertilizer by sugarcane growers, due to its potential to
      completely replace mineral fertilizers. However, if the application is not
      adequate, this practice may cause environmental contamination. This study used a
      respirometry test to evaluate the organic matter (OM) decomposition present in
      natural vinasse and concentrated vinasse (CV), with or without urea addition. The
      experiment involved two soil types and two types of vinasse at different
      application rates. The vinasse chemical characterization showed high levels of
      pseudo-total potassium (K) in both vinasses, which are not considered in the
      application rates. Decomposition rates above 90% and between 70 and 80% were
      obtained for sandy and clayey soils, respectively, over a brief 41-day period,
      indicating rapid OM decomposition. Positive priming effect was observed for CV
      and CV + urea treatments in sandy soil. An important implication of these
      findings revealed that K not available in vinasse was released in the soil
      solution by the OM mineralization, indicating the possibility of overestimation
      in the vinasse application rates. Therefore, K pseudo-total values should be
      considered in the calculation of the vinasse application rates. However, studies
      involving K mobility into soil are needed to validate this hypothesis.

PMID- 28759456
TI  - Experimental study of using wastewater sludge as a new drag reduction agent.
AB  - Siltation is considering as a huge risk to the life and security of dams. Forced
      to preserve their useful volumes, managers use sediment dredging operations
      through different techniques. The aim of our work is to investigate the
      wastewater sludge derived from wastewater treatment as a new natural lubricating
      instrument during transport of sediment in the pipes and to reduce head losses.
      From an economic and environmental point of view, this technique is more
      effective than the use of industrial polymers. The rheological study is done
      using an RS600 rheometer. Head losses and friction reducing are measured on three
      horizontal pipes (30, 50 and 80 mm). The mud from the dam and sludge are added at
      different volumes concentrations. The results revealed that the mud follows the
      Herschel-Bulkley model at 10-20% volume concentration, even after adding
      wastewater sludge proportions from 0.1- 0.4%. The mud flow head losses in pipes
      increase with increasing solids concentration. A maximum reduction in yield
      stress and frictional head loss are observed at 0.25 to 0.35% of sludge
      concentration, which can be the most effective choice.

PMID- 28759457
TI  - Genetic causes of sudden cardiac death in children: inherited arrhythmogenic
      diseases.
AB  - PURPOSE OF REVIEW: In this chapter we will discuss the most recent and relevant
      evidences published in the field of inherited arrhythmogenic disorders, focusing
      on the so called 'channelopathies' that are associated with sudden cardiac death
      (SCD) in children: long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada
      syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT).
      RECENT FINDINGS: We will discuss the latest diagnostic criteria for
      channelopathies released by the European Society of Cardiology, the new data on
      BrS in children and the recent evidence supporting a genotype-specific therapy
      for LQTS type 3. Moreover, we will present further insights into the risk
      stratification of the children affected by LQTS, analyzing the role of imaging
      for the prediction of life-threatening arrhythmias. In addition, we will offer a
      perspective on how to deal with genetic results in families affected by SCD at
      very young ages. SUMMARY: The selected publications will aid pediatricians in
      their clinical work when managing little patients with inherited arrhythmias,
      providing the most recent information for diagnosis, risk stratification, and
      management.

PMID- 28759458
TI  - Pharyngolaryngeal symptoms associated with thyroid disease.
AB  - PURPOSE OF REVIEW: The current review summarizes previous reports on
      laryngopharyngeal symptoms associated with thyroid disease. This review also
      includes pharyngolaryngeal symptoms caused by thyroidectomy. However, we focus on
      pharyngolaryngeal symptoms following uncomplicated thyroidectomy, as this is an
      important issue in the fields of otolaryngology. RECENT FINDINGS: An enlarged
      thyroid gland, as in thyroiditis, multinodular goiter, or large nodules, can
      cause compressive symptoms. Malignant nodules invading the recurrent laryngeal
      nerve and benign nodules compressing the nerve can cause vocal cord paralysis and
      hoarseness. Pharyngolaryngeal symptoms are known to develop after a
      thyroidectomy, generally as a result of injury to the superior or recurrent
      laryngeal nerve. However, recent studies have shown that various
      pharyngolaryngeal symptoms, such as globus symptoms and voice changes, occur
      after thyroidectomy in the absence of laryngeal nerve injury. These symptoms are
      known collectively as postthyroidectomy syndrome. Several possible explanations
      have been proposed and evaluated for postthyroidectomy syndrome. SUMMARY: Several
      thyroid disorders can cause compressive symptoms and hoarseness. Superior and/or
      recurrent laryngeal nerve injury during thyroidectomy is the main cause of
      various pharyngolaryngeal symptoms. However, other pharyngolaryngeal symptoms
      that arise following thyroidectomy in the absence of nerve injury, a condition
      known as postthyroidectomy syndrome, are becoming more common.

PMID- 28759459
TI  - Anterior compartment prolapse: what's new?
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize the treatment
      options for anterior compartment prolapse, describe the role that apical
      suspension plays in the correction of anterior vaginal wall prolapse, and assess
      the risks and benefits of biologic and synthetic graft use in anterior
      compartment repair. RECENT FINDINGS: In 2016, The Cochrane Review published a
      review of 37 trials including 4023 participants finding that compared to native
      tissue repair, the use of synthetic mesh resulted in reduced symptomatic prolapse
      recurrence, anatomic recurrence, and repeat prolapse surgery. There was
      insufficient evidence regarding quality of life improvement or the use of
      biologic grafts. Of note the differences between native tissue and mesh kit
      repairs were not large. SUMMARY: A strong consideration should be on the
      correction of apical prolapse when present; isolated anterior wall repairs should
      be pursued with caution. The surgeon may consider the use of augmenting materials
      in their repair of anterior vaginal wall prolapse, although the available
      evidence is not strongly supportive of their use given potential risks.

PMID- 28759460
TI  - Management of benign ovarian lesions in girls: a trend toward fewer
      oophorectomies.
AB  - PURPOSE OF REVIEW: The management of benign ovarian lesions in girls is currently
      a controversial topic in the pediatric surgical literature. The purpose of this
      review is to highlight the epidemiology of benign ovarian masses, outline
      preoperative risk stratification strategies, review the indications and
      importance of ovary-sparing surgery (OSS), and discuss the impact of management
      algorithms. RECENT FINDINGS: Efforts across the United States and Canada to
      promote OSS have improved awareness about the role and safety of OSS for the
      management of benign ovarian masses in pediatric and adolescent girls.
      Preoperative risk stratification techniques by a multidisciplinary team can
      improve the preoperative identification of lesions with a high likelihood of
      benign disease. SUMMARY: Avoiding oophorectomy may be associated with a number of
      benefits to individual patients and the overall population. The implementation of
      a management algorithm to guide the treatment of pediatric and adolescent girls
      with ovarian lesions can reduce the rate of inappropriate oophorectomies.

PMID- 28759461
TI  - Lasers for pelvic floor dysfunctions: is there evidence?
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss the available energy
      sources used in the vaginal canal that are currently being promoted for certain
      pelvic floor conditions and explore the body of peer-reviewed literature
      supporting their use. RECENT FINDINGS: The majority of research has focused on
      the use of fractional CO2 laser treatment for genitourinary syndrome of menopause
      (GSM). Most of these studies are nonrandomized prospective studies, but their
      data consistently shows an improvement in symptoms without significant side
      effects. SUMMARY: Vaginal laser treatment for GSM is of particular interest to
      gynecologists as it provides patients with a history of estrogen receptor
      positive breast cancer, thromboembolic event, or other contraindication to
      hormone therapy, an effective treatment option. Currently, we are in the early
      stages of scientific investigation into the use of lasers in the treatment of
      pelvic floor dysfunction, but the emerging data is encouraging. The existing data
      is limited to mostly observational studies with additional quality randomized
      controlled trials and sham studies needed to ensure that physicians are providing
      the optimum evidence-based treatments to their patients. At the present time
      there is insufficient data to promote these therapies for stress incontinence,
      vaginal tightening, or other pelvic floor abnormalities.

PMID- 28759462
TI  - Pig islet xenotransplantation.
AB  - PURPOSE OF REVIEW: The current article reviews the rationale, sources and
      preparation of pig islets for xenotransplantation, and presents current progress
      in solving the problems associated with establishing pig islet transplant as a
      clinical treatment for type 1 diabetes. SUMMARY: Islet transplantation is an
      effective treatment option for type 1 diabetes, but the available supply of human
      pancreases is insufficient to meet the need and demand for obtaining islets. Pig
      islets provide a readily available source for islet transplantation, with trials
      in non-human primates demonstrating their potential to reverse diabetes. The risk
      of zoonosis can be reduced by designated pathogen-free breeding of the donor
      pigs, but porcine endogenous retroviruses (PERVs) that are integrated into the
      genome of all pigs are especially difficult to eliminate. However, clinical
      trials have demonstrated an absence of PERV transmission with a significant
      reduction in the number of severe hypoglycemic episodes and up to 30% reduction
      in exogenous insulin doses. A number of methods such as production of various
      transgenic pigs to better xenotransplantation efficiency and the encapsulation of
      islets to isolate them from the host immune system are currently being tested to
      overcome the xenograft immune rejection. Furthermore, ongoing research is also
      shedding light on factors such as the age and breed of the donor pig to determine
      the optimal islet quantity and function.

PMID- 28759463
TI  - Immunosuppression maintenance in vascularized composite allotransplantation: what
      is just right?
AB  - PURPOSE OF REVIEW: Over the last two decades advances in vascularized composite
      allotransplantation have achieved clinically significant milestones. This review
      provides a synopsis for immunosuppressive maintenance therapy for VCA and
      discusses the nuances surrounding the determination of the right amount of
      immunosuppression in vascularized composite allotransplantation. RECENT FINDINGS:
      Functional results after vascularized composite allotransplantation remain highly
      encouraging as are the immunologic outcomes, however, challenges persist.
      Currently, although conventional immunosuppressive protocols have been successful
      at preventing allograft loss; they have not totally prevented episodes of acute
      rejection in the skin. Furthermore, vascularized composite allotransplantation
      carries a significant risk profile attributed to the complications of life-long,
      high-dose immunosuppression regimens. SUMMARY: Examining conventional treatment
      protocols can lead to the development of novel immunosuppression concepts that
      will ultimately assist in favorably tilting the risk-benefit scale for these life
      changing transplants.

PMID- 28759464
TI  - Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.
AB  - BACKGROUND: Esketamine is traditionally administered via intravenous or
      intramuscular routes. In this study we developed a pharmacokinetic model of
      inhalation of nebulized esketamine with special emphasis on pulmonary absorption
      and bioavailability. METHODS: Three increasing doses of inhaled esketamine (dose
      escalation from 25 to 100 mg) were applied followed by a single intravenous dose
      (20 mg) in 19 healthy volunteers using a nebulizer system and arterial
      concentrations of esketamine and esnorketamine were obtained. A
      multicompartmental pharmacokinetic model was developed using population nonlinear
      mixed-effects analyses. RESULTS: The pharmacokinetic model consisted of three
      esketamine, two esnorketamine disposition and three metabolism compartments. The
      inhalation data were best described by adding two absorption pathways, an
      immediate and a slower pathway, with rate constant 0.05 +/- 0.01 min (median +/-
      SE of the estimate). The amount of esketamine inhaled was reduced due to dose
      independent and dose-dependent reduced bioavailability. The former was 70% +/-
      5%, and the latter was described by a sigmoid EMAX model characterized by the
      plasma concentration at which absorption was impaired by 50% (406 +/- 46 ng/ml).
      Over the concentration range tested, up to 50% of inhaled esketamine is lost due
      to the reduced dose-independent and dose-dependent bioavailability. CONCLUSIONS:
      We successfully modeled the inhalation of nebulized esketamine in healthy
      volunteers. Nebulized esketamine is inhaled with a substantial reduction in
      bioavailability. Although the reduction in dose-independent bioavailability is
      best explained by retention of drug and particle exhalation, the reduction in
      dose-dependent bioavailability is probably due to sedation-related loss of drug
      into the air.

PMID- 28759467
TI  - Bringing implementation science to the intensive care unit.

PMID- 28759466
TI  - The current status of biomarkers for the diagnosis of nosocomial pneumonias.
AB  - PURPOSE OF REVIEW: Nosocomial pneumonia is a frequent and severe nosocomial
      infection divided in two distinct groups: hospital-acquired pneumonia and
      ventilator-associated pneumonia (VAP). In this context, the VAP is notoriously
      difficult to diagnose clinically, resulting from the lack of a 'gold standard'
      method of diagnosis. RECENT FINDINGS: The use of biomarkers may potentially
      improve the early diagnosis of infections allowing earlier and better
      identification and treatment. An exhausting list of biomarkers has been studied
      and although far from perfect, procalcitonin (PCT) and C-reactive protein (CRP)
      are the most studied biomarkers used in clinical practice. Data coming from
      literature suggests the use of PCT for VAP prognosis and as a based algorithm
      tool for the reduction of duration of pneumonia therapy, as well as, the use of
      the CRP dynamics to the early prediction of VAP and the response to the
      antibiotics. SUMMARY: The evidence for the use of biomarkers to diagnose
      nosocomial pneumonia as a stand-alone tool is low to moderate. Improved
      performance for both PCT and CRP can be obtained by using them in association
      with clinical features or scoring systems but prospective studies are still
      needed to validate this hypothesis.

PMID- 28759468
TI  - The evaluation of critically ill transplant patients with infectious diarrhea.
AB  - PURPOSE OF REVIEW: The review summarizes the epidemiology, risk factors, clinical
      presentation, diagnosis and management of the most important etiologic agents of
      infectious diarrhea in critically ill transplant recipients. RECENT FINDINGS:
      Diarrhea, frequently caused by infectious pathogens, can cause significant
      morbidity and mortality in transplant recipients. Diarrhea can lead to severe
      dehydration, acute renal failure, medication toxicity, rejection, graft-versus
      host disease and impairs patients' quality of life. Opportunistic infectious
      pathogens can pose significant diagnostic and therapeutic challenges in
      immunocompromised hosts. SUMMARY: In transplant recipients, it is vital to
      differentiate infectious from noninfectious diarrhea to adequately manage their
      therapeutic approach. Supportive measures and reduction in immunosuppression are
      essential for the treatment management.

PMID- 28759469
TI  - What is new in the prevention of nosocomial pneumonia in the ICU?
AB  - PURPOSE OF REVIEW: To summarize and contextualize recent evidence on preventing
      ventilator-associated pneumonia (VAP). RECENT FINDINGS: Many centers continue to
      report dramatic decreases in VAP rates after implementing ventilator bundles.
      Interpreting these reports is complicated, however, by the subjectivity and lack
      of specificity of VAP definitions. More objective data suggest VAP rates may not
      have meaningfully changed over the past decade. If so, this compels us to re
      examine and revise the prevention bundles we have been using to prevent VAP. New
      analyses suggest that most hospitals' ventilator bundles include a mix of helpful
      and potentially harmful elements. Spontaneous awakening trials, spontaneous
      breathing trials, head-of-bed elevation, and thromboprophylaxis appear
      beneficial. Oral chlorhexidine and stress ulcer prophylaxis may be harmful.
      Subglottic secretion drainage, probiotics, and novel endotracheal cuff designs do
      not clearly improve objective outcomes. Selective digestive decontamination by
      contrast appears to lower VAP and mortality rates. Effective implementation is as
      important as choosing the right bundle components. Best practices include
      engaging and educating staff, creating structures that facilitate bundle
      adherence, and providing regular feedback on process measure performance and
      outcome rates. SUMMARY: VAP rates may still be elevated despite multiple reports
      to the contrary. Recent evidence suggests new ways to optimize the selection of
      ventilator bundle components and their implementation.

PMID- 28759470
TI  - Percutaneous coronary intervention strategies in patients with ST-segment
      elevation myocardial infarction and multivessel coronary artery disease.
AB  - PURPOSE OF REVIEW: This review aims to summarize recent reports on percutaneous
      coronary intervention (PCI) strategies for patients with ST-elevation myocardial
      infarction (STEMI) and multivessel coronary artery disease (CAD). RECENT
      FINDINGS: Recent randomized clinical trials and meta-analyses have suggested that
      patients with STEMI and multivessel CAD may benefit more from multivessel PCI
      (either multivessel primary PCI or staged PCI before hospital discharge) than
      culprit vessel-only primary PCI. These reports have changed clinical practice
      guideline recommendations that now conclude that multivessel PCI may be
      considered in selected hemodynamically stable patients with significant
      noninfarct artery stenoses based on anatomic criteria alone. Fractional flow
      reserve measurement can document functional significance in nonculprit stenoses,
      but fractional flow reserve-guided PCI has not been shown to impact mortality or
      myocardial infarction rates. Additionally, nonculprit artery chronic total
      occlusion PCI was not effective in improving left ventricular function in one
      randomized trial. SUMMARY: Multivessel primary PCI or staged PCI is effective and
      safe in selected patients with STEMI and multivessel coronary disease. Future
      randomized controlled trials are needed to define the optimal timing of
      multivessel PCI, as well as the appropriate use of PCI in nonculprit stenoses.

PMID- 28759471
TI  - The Ross procedure in adults: which patients, which disease?
AB  - PURPOSE OF REVIEW: The purpose of this article is to review the contemporary
      evidence surrounding the use of the Ross procedure in young and middle-aged
      adults and to identify the subset patients who are most likely to derive a
      benefit from this operation. RECENT FINDINGS: In appropriately selected young and
      middle-aged adults undergoing aortic valve replacement (AVR), the Ross procedure
      is currently the only operation that can restore long-term survival that is
      equivalent to that of the age-matched healthy general population. The ideal
      patient for the Ross procedure is a young, otherwise healthy adult with aortic
      stenosis and a small or normal size aortic annulus. In addition, this operation
      is particularly valuable in women contemplating pregnancy and patients with high
      level of physical activity, as well as those who wish to avoid the burden of
      lifelong anticoagulation. When carried out in expert centers with adequate
      surgical volumes, the Ross procedure is associated with superior long-term
      outcomes compared with prosthetic AVR, with minimal cost in terms of early
      morbidity and mortality. SUMMARY: Despite the expanding body of evidence
      demonstrating its long-term superiority over conventional prosthetic AVR in
      appropriately selected patients, the Ross operation remains largely underused.
      This situation mandates careful reexamination of current practice guidelines.

PMID- 28759472
TI  - Macrophage complexity in human atherosclerosis: opportunities for treatment?
AB  - PURPOSE OF REVIEW: The pivotal role of macrophages in experimental
      atherosclerosis is firmly established, but their contribution to human disease is
      less well defined. In this review we have outlined the current insights on
      macrophage phenotypes and their presumed precursors, monocytes, in clinical
      atherosclerosis, and their association with disease progression. Moreover, we
      will assess major clinical modifiers of macrophage-mediated plaque inflammation
      and define the outstanding questions for further study. RECENT FINDINGS: Our
      survey indicates that macrophage accumulation and status in human plaques are
      linked with lesion progression and destabilization as well as with symptomatic
      coronary artery disease. Likewise, levels of their precursors, circulating
      monocytes were repeatedly seen to associate with atherosclerosis and to predict
      clinical outcome. Furthermore, the presence and phenotype of both macrophages and
      monocytes appears to be responsive to the traditional risk factors of
      atherosclerosis, including hypercholesterolemia, hypertension, and type 2
      diabetes, and to treatment thereof, with clear repercussions on disease
      development. SUMMARY: Although plaque macrophages and their precursor cells do
      represent attractive targets for treating cardiovascular diseases, this
      therapeutic avenue requires much deeper understanding of the complexity of
      macrophage biology in human atherosclerosis than available at present.

PMID- 28759473
TI  - Novel therapeutic approaches for thrombotic thrombocytopenic purpura.
AB  - PURPOSE OF REVIEW: Acquired thrombotic thrombocytopenic purpura is an immune
      mediated thrombotic microangiopathy caused by antibodies to ADAMTS13 (A
      Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13).
      Standard treatment with therapeutic plasma exchange and immunosuppression with
      steroids results in high remission and low mortality rates. However, a number of
      patients remain refractory to frontline therapy and/or experience multiple
      relapses. This study reviews emerging therapies for thrombotic thrombocytopenic
      purpura. RECENT FINDINGS: Studies indicate that reducing anti-ADAMTS13 antibody
      levels through B-cell depletion or proteasome inhibition is effective for the
      management of refractory disease. Preliminary reports examining anti-CD20 therapy
      for the treatment of initial disease or as maintenance therapy for seropositive
      patients suggest the addition of immunosuppression in other disease phases may
      delay relapse. Exciting developments in targeted therapies to von Willebrand
      Factor and recombinant ADAMTS13 hold promise for transforming disease management.
      SUMMARY: Approximately half of patients diagnosed with acquired thrombotic
      thrombocytopenic purpura experience refractory and/or relapsing disease. For
      these patients, a hematologic remission may be an insufficient therapeutic goal.
      With recent developments, it is now possible to envision a multifaceted approach
      targeting disease mechanisms that may dramatically improve outcomes for this
      otherwise debilitating disease.

PMID- 28759474
TI  - Quick Sequential Organ Failure Assessment and Systemic Inflammatory Response
      Syndrome Criteria as Predictors of Critical Care Intervention Among Patients With
      Suspected Infection.
AB  - OBJECTIVES: The Sepsis III clinical criteria for the diagnosis of sepsis rely on
      scores derived to predict inhospital mortality. In this study, we introduce the
      novel outcome of "received critical care intervention" and investigate the
      related predictive performance of both the quick Sequential Organ Failure
      Assessment and the Systemic Inflammatory Response Syndrome criteria. DESIGN: This
      was a single-center, retrospective analysis of electronic health records.
      SETTING: Tertiary care hospital in the United States. PATIENTS: Patients with
      suspected infection who presented to the emergency department and were admitted
      to the hospital between January 2010 and December 2014. INTERVENTIONS: Systemic
      Inflammatory Response Syndrome and quick Sequential Organ Failure Assessment
      scores were calculated, and their relationships to the receipt of critical care
      intervention and inhospital mortality were determined. MEASUREMENT AND MAIN
      RESULTS: A total of 24,164 patients were included of whom 6,693 (27.7%) were
      admitted to an ICU within 48 hours; 4,453 (66.5%) patients admitted to the ICU
      received a critical care intervention. Among those with quick Sequential Organ
      Failure Assessment less than 2, 13.4% received a critical care intervention and
      3.5% died compared with 48.2% and 13.4%, respectively, for quick Sequential Organ
      Failure Assessment greater than or equal to 2. The area under the receiver
      operating characteristic was similar whether quick Sequential Organ Failure
      Assessment was used to predict receipt of critical care intervention or
      inhospital mortality (0.74 [95% CI, 0.73-0.74] vs 0.71 [0.69-0.72]). The area
      under the receiver operating characteristic of Systemic Inflammatory Response
      Syndrome for critical care intervention (0.69) and mortality (0.66) was lower
      than that for quick Sequential Organ Failure Assessment (p < 0.001 for both
      outcomes). The sensitivity of quick Sequential Organ Failure Assessment for
      predicting critical care intervention was 38%. CONCLUSIONS: Emergency department
      patients with suspected infection and low quick Sequential Organ Failure
      Assessment scores frequently receive critical care interventions. The
      misclassification of these patients as "low risk," in combination with the low
      sensitivity of quick Sequential Organ Failure Assessment greater than or equal to
      2, may diminish the clinical utility of the quick Sequential Organ Failure
      Assessment score for patients with suspected infection in the emergency
      department.

PMID- 28759476
TI  - Aquatic Exercises in the Treatment of Low Back Pain: A Systematic Review of the
      Literature and Meta-Analysis of Eight Studies.
AB  - OBJECTIVE: Low back pain is the most common musculoskeletal condition with a high
      prevalence. There was no sufficient evidence to recommend that aquatic exercise
      was potentially beneficial to patients with low back pain. The aim of this study
      was to systematically analyze all evidence available in the literature about
      effectiveness of the aquatic exercise. DESIGN: A comprehensive search of PubMed,
      the Cochrane Library, Embase, and Cumulative Index to Nursing and Allied Health
      was conducted from their inceptions to November 2016 for randomized controlled
      trials, which concerned the therapeutic aquatic exercise for low back pain. The
      results were expressed in terms of standardized mean difference and the
      corresponding 95% confidence interval. RESULTS: Eight trials involving 331
      patients were included in the meta-analysis, and the results showed a relief of
      pain (standardized mean difference = -0.65, 95% confidence interval = -1.16 to 
      0.14) and physical function (standardized mean difference = 0.63, 95% confidence
      interval = 0.17 to 1.09) after aquatic exercise. However, there was no
      significant effectiveness with regard to general mental health in aquatic group
      (standardized mean difference = 0.46; 95% confidence interval = -0.22 to 1.15).
      CONCLUSIONS: Aquatic exercise can statistically significantly reduce pain and
      increase physical function in patients with low back pain. Further high-quality
      investigations on a larger scale are required to confirm the results.

PMID- 28759475
TI  - Component resolved diagnostics for hymenoptera venom allergy.
AB  - PURPOSE OF REVIEW: Component-resolved diagnostics makes use of defined allergen
      molecules to analyse IgE-mediated sensitizations at a molecular level. Here, we
      review recent studies on the use of component-resolved diagnostics in the field
      of Hymenoptera venom allergy (HVA) and discuss its benefits and limitations.
      RECENT FINDINGS: Component resolution in HVA has moved from single molecules to
      panels of allergens. Detection of specific immunoglobulin E (sIgE) to marker and
      cross-reactive venom allergens has been reported to facilitate the discrimination
      between primary sensitization and cross-reactivity and thus, to provide a better
      rationale for prescribing venom immunotherapy (VIT), particularly in patients
      sensitized to both honeybee and vespid venom. Characterization of IgE reactivity
      to a broad panel of venom allergens has allowed the identification of different
      sensitization profiles that in honeybee venom allergy were associated with
      increased risks for side effects or treatment failure of VIT. In contrast,
      component resolution so far has failed to provide reliable markers for the
      discrimination of sensitizations to venoms of different members of Vespidae.
      SUMMARY: Component-resolved diagnostics allows a better understanding of the
      complexity of sensitization and cross-reactivities in HVA. In addition, the
      enhanced resolution and precision may allow identification of biomarkers, which
      can be used for risk stratification in VIT. Knowledge about the molecular
      composition of different therapeutic preparations may enable the selection of
      appropriate preparations for VIT according to individual sensitization profiles,
      an approach consistent with the goals of personalized medicine.

PMID- 28759477
TI  - Second-Order Peer Reviews of Clinically Relevant Articles for the Physiatrist:
      Additional Weekend Therapy May Reduce Length of Rehabilitation Stay After Stroke:
      A Meta-analysis of Individual Patient Data.

PMID- 28759478
TI  - The Effects of Orientation of Lumbar Facet Joints on the Facet Joint Contact
      Forces: An In Vitro Biomechanical Study.
AB  - STUDY DESIGN: A biomechanical human cadaveric study. OBJECTIVE: The aim of this
      study was to measure L2-L3 facet joint contact forces in a flexibility test using
      thin film electroresistive sensors, and facet joint orientation on computed
      tomographic (CT) scan images, to examine the effects of orientation of lumbar
      facet joint on the facet joint contact forces. SUMMARY OF BACKGROUND DATA:
      Biomechanically, the bilateral facet joints play a critical role in maintaining
      stability of the lumbar spine. The effect of orientation of lumbar facet joints
      on the contact forces remains unknown. METHODS: Eight human cadaveric lumbar
      spine specimens (L2-L3) were tested by applying a pure moment of +/-7.5 Nm in
      three directions of loading (flexion-extension, lateral bending, and axial
      rotation) with and without a follower preload of 300 N. The orientation of the
      lumbar facet joints at the L2-L3 was measured on axial CT scans. Bilateral facet
      contact forces were measured during flexibility tests using thin film
      electroresistive sensors (Tekscan 6900). RESULTS: The average total peak facet
      loads was 66 N in axial rotation, 27 N in extension, and 20 N in lateral bending
      under a pure moment. Under a pure moment with a follower preload of 300 N, the
      average total peak facet loads was 53 N in axial rotation, 43 N in extension, and
      24 N in lateral bending. The facet joint forces were correlated positively and
      significantly with the orientation in all directions with and without a
      compressive follower preload (P < 0.05). In addition, the facet joint contact
      forces at neutral position with a follower preload were correlated positively
      with the orientation (rs = 0.759, P = 0.001). CONCLUSION: This study identified
      that the greater coronal orientation of lumbar facet joints is, the higher the
      facet joint contact forces are. LEVEL OF EVIDENCE: 3.

PMID- 28759479
TI  - Bipolar Disorder and Early Emotional Trauma: A Critical Literature Review on
      Indicators of Prevalence Rates and Clinical Outcomes.
AB  - LEARNING OBJECTIVES: After participating in this activity, learners should be
      better able to:* Evaluate the prevalence of early emotional trauma in patients
      with bipolar disorder (BD)* Assess the impact of these traumas on patients and on
      their development of BD OBJECTIVES: We performed a systematic literature review
      to (1) evaluate the prevalence of early emotional trauma (EET) in patients with
      bipolar disorder (BD) and the impact of these traumas on the development of the
      disorder, and (2) integrate the findings of our review with those previously
      reported by Fisher and Hosang, Daruy-Filho and colleagues, and Maniglio. METHODS:
      The literature search was performed on PubMed, SciELO, and PsycINFO databases
      using the keywords bipolar disorder, early trauma, physical abuse, emotional
      abuse, sexual abuse, maltreatment, adversity, and neglect. RESULTS: Twenty-eight
      articles were selected and analyzed. Taken together, the articles described a
      high prevalence of EET in BD, consisting mainly of emotional neglect/abuse
      (approximately 40%), particularly when compared to healthy subjects. The review
      also identified substantial evidence regarding an association between the
      presence of EET, early disease onset, rapid cycling, comorbidity with
      anxiety/stress disorders, and cannabis use. CONCLUSION: The integration of the
      current findings with the identified studies reveals that (1) the methodological
      limitations noted by Daruy-Filho and colleagues have been largely resolved in
      more recent studies and (2) the presence of EET in patients with BD is associated
      with worse clinical outcomes, particularly early disease onset, presence of
      clinical or psychiatric comorbidities, suicide, and presence of psychotic
      episodes/symptoms. The review shows that patients with BD experience more
      traumatic situations than controls and that emotional trauma is the most frequent
      type of trauma in this group.

PMID- 28759480
TI  - Metal Exposure in Veterans With Embedded Fragments From War-Related Injuries:
      Early Findings From Surveillance Efforts.
AB  - OBJECTIVE: To characterize systemic metal exposures from retained fragments in a
      cohort of war-injured US Veterans enrolled in the Department of Veterans Affairs'
      Embedded Fragment Registry. METHODS: Five hundred seventy nine registry-enrolled
      Veterans submitted an exposure questionnaire and urine sample for analyses of 14
      metals often found in fragments. Urine metal results were compared with reference
      values of unexposed populations to identify elevations. RESULTS: 55% of Veterans
      had normal urine metal values. When observed, tungsten and zinc were the metals
      most frequently elevated, followed by cobalt; however, cobalt levels were not
      associated with a fragment source, but with surgical implants present.
      CONCLUSIONS: Though most metal elevations observed are not significantly outside
      the normal range, on-going accrual of metal burdens in these Veterans over time
      recommends continued surveillance which may inform future medical management.

PMID- 28759481
TI  - Influenza and Workplace Productivity Loss in Working Adults.
AB  - OBJECTIVE: Few studies have examined how acute respiratory illnesses (ARI)
      influence workplace productivity. We examined the association between laboratory
      confirmed influenza and combined absenteeism/presenteeism. METHODS: Linear
      regression was used to model the association between influenza (by seasonal
      vaccine status) and productivity loss over 7 to 17 days following symptom onset
      in 1278 employed adults in an influenza vaccine effectiveness study during the
      2012 to 2013 through 2015 to 2016 seasons. RESULTS: Influenza was significantly
      associated with workplace productivity loss (P < 0.001), but there were no
      significant differences between virus type/subtypes or seasonal vaccine status.
      Regardless of vaccination, participants with H1N1pdm09, H3N2, or B infection had
      the greatest mean productivity loss (range, 67% to 74%), while those with non
      influenza ARI had the lowest productivity loss (58% to 59%). CONCLUSIONS:
      Compared with non-influenza ARI, those with influenza lose an additional half day
      of work due to absenteeism/presenteeism over the week following symptom onset.

PMID- 28759482
TI  - Clonidine Increases the Likelihood That Abstinence Can Withstand Unstructured
      Time in Buprenorphine-maintained Outpatients.
AB  - OBJECTIVE: In a clinical trial examining daily clonidine as an adjunct to
      buprenorphine treatment for opioid dependence, we found that clonidine increased
      opioid abstinence and decoupled stress from craving. From a personalized-medicine
      perspective, the next step is to identify people for whom clonidine would be
      beneficial. To that end, using data from the same clinical trial, we examined the
      associations of daily-life activities with treatment success. METHODS:
      Outpatients (N = 118) received clonidine (0.3 mg/d) or placebo during 18 weeks of
      buprenorphine treatment. Participants carried a smartphone that randomly prompted
      them 4 times per day to report their moods and activities. Using generalized
      linear mixed models, we assessed the likelihoods of different types of daily
      activity as a function of clonidine versus placebo, days of longest continuous
      opioid abstinence, and their interaction. RESULTS: Participants in the
      buprenorphine-only (buprenorphine plus placebo) control group who engaged in more
      responsibilities (work and child/elder care) had longer streaks of abstinence,
      whereas those who engaged in more unstructured-time activities had shorter
      streaks of abstinence. Conversely, for participants in the buprenorphine-plus
      clonidine group, longer streaks of abstinence were associated with higher
      frequencies of activities associated with "unstructured" time. CONCLUSIONS: The
      study replicates findings that engaging in responsibilities is related to
      positive treatment outcomes in standard opioid agonist therapy. The pattern of
      results also suggests that clonidine helped participants engage in unstructured
      time activities with less risk of craving or use than they might otherwise have
      had.

PMID- 28759483
TI  - Alarm Limits for Intraoperative Drug Infusions: A Report From the Multicenter
      Perioperative Outcomes Group.
AB  - BACKGROUND: Continuous medication infusions are commonly used during surgical
      procedures. Alarm settings for infusion pumps are considered important for
      patient safety, but limits are not created in a standardized manner from actual
      usage data. We estimated 90th and 95th percentile infusion rates from a national
      database for potential use as upper limit alarm settings. METHODS: We extracted
      infusion rate data from 17 major hospitals using intraoperative records provided
      by Multicenter Perioperative Outcomes Group for adult surgery between 2008 and
      2014. Seven infusions were selected for study: propofol, remifentanil,
      dexmedetomidine, norepinephrine, phenylephrine, nitroglycerin, and esmolol. Each
      dosage entry for an infusion during a procedure was included. We estimated the
      50th, 90th, and 95th percentile levels for each infusion across institutions, and
      performed quantile regression to examine factors that might affect the
      percentiles rates, such as use in general anesthesia versus sedation. RESULTS:
      The median 90th and 95th percentile infusion rates (with interquartile range) for
      propofol were 150 (140-150) and 170 (150-200) MUg/kg/min. Quantile regression
      demonstrated higher 90th and 95th percentile rates during sedation for
      gastrointestinal endoscopy than for all surgical procedures performed under
      general anesthesia. For selected vasoactive medications, the corresponding median
      90th and 95th percentile rates (with interquartile range) were norepinephrine
      14.0 (9.8-18.1) and 18.3 (12.6-23.9) MUg/min, and phenylephrine 60 (55-80) and 80
      (75-100) MUg/min. CONCLUSIONS: Alarm settings based on infusion rate percentile
      limits would be triggered at predictable rates; ie, the 95th percentile would be
      exceeded and an alarm sounded during 1 in 20 infusion rate entries. As a result,
      institutions could establish pump alarm settings consistent with desired alarm
      frequency using their own or externally validated usage data. Further study will
      be needed to determine the optimal percentile for infusion alarm settings.

PMID- 28759484
TI  - Impact of Different Ventilation Strategies on Driving Pressure, Mechanical Power,
      and Biological Markers During Open Abdominal Surgery in Rats.
AB  - BACKGROUND: Intraoperative mechanical ventilation may yield lung injury. To date,
      there is no consensus regarding the best ventilator strategy for abdominal
      surgery. We aimed to investigate the impact of the mechanical ventilation
      strategies used in 2 recent trials (Intraoperative Protective Ventilation
      [IMPROVE] trial and Protective Ventilation using High versus Low PEEP [PROVHILO]
      trial) on driving pressure (DeltaPRS), mechanical power, and lung damage in a
      model of open abdominal surgery. METHODS: Thirty-five Wistar rats were used, of
      which 28 were anesthetized, and a laparotomy was performed with standardized
      bowel manipulation. Postoperatively, animals (n = 7/group) were randomly assigned
      to 4 hours of ventilation with: (1) tidal volume (VT) = 7 mL/kg and positive end
      expiratory pressure (PEEP) = 1 cm H2O without recruitment maneuvers (RMs) (low
      VT/low PEEP/RM-), mimicking the low-VT/low-PEEP strategy of PROVHILO; (2) VT = 7
      mL/kg and PEEP = 3 cm H2O with RMs before laparotomy and hourly thereafter (low
      VT/moderate PEEP/4 RM+), mimicking the protective ventilation strategy of
      IMPROVE; (3) VT = 7 mL/kg and PEEP = 6 cm H2O with RMs only before laparotomy
      (low VT/high PEEP/1 RM+), mimicking the strategy used after intubation and before
      extubation in PROVHILO; or (4) VT = 14 mL/kg and PEEP = 1 cm H2O without RMs
      (high VT/low PEEP/RM-), mimicking conventional ventilation used in IMPROVE. Seven
      rats were not tracheotomized, operated, or mechanically ventilated, and
      constituted the healthy nonoperated and nonventilated controls. RESULTS: Low
      VT/moderate PEEP/4 RM+ and low VT/high PEEP/1 RM+, compared to low VT/low PEEP/RM
      and high VT/low PEEP/RM-, resulted in lower DeltaPRS (7.1 +/- 0.8 and 10.2 +/-
      2.1 cm H2O vs 13.9 +/- 0.9 and 16.9 +/- 0.8 cm H2O, respectively; P< .001) and
      less mechanical power (63 +/- 7 and 79 +/- 20 J/min vs 110 +/- 10 and 120 +/- 20
      J/min, respectively; P = .007). Low VT/high PEEP/1 RM+ was associated with less
      alveolar collapse than low VT/low PEEP/RM- (P = .03). E-cadherin expression was
      higher in low VT/moderate PEEP/4 RM+ than in low VT/low PEEP/RM- (P = .013) or
      high VT/low PEEP/RM- (P = .014). The extent of alveolar collapse, E-cadherin
      expression, and tumor necrosis factor-alpha correlated with DeltaPRS (r = 0.54 [P
      = .02], r = -0.48 [P = .05], and r = 0.59 [P = .09], respectively) and mechanical
      power (r = 0.57 [P = .02], r = -0.54 [P = .02], and r = 0.48 [P = .04],
      respectively). CONCLUSIONS: In this model of open abdominal surgery based on the
      mechanical ventilation strategies used in IMPROVE and PROVHILO trials, lower
      mechanical power and its surrogate DeltaPRS were associated with reduced lung
      damage.

PMID- 28759486
TI  - Avoiding Complications From Patient Positioning for Intraocular Surgery.
AB  - Collaboration of the surgical and anesthesia teams for patient positioning is
      essential to assure patient comfort and safety, preventing systemic and
      ophthalmic complications. The goals and rationales of positioning for intraocular
      surgery are discussed including placing the head above the heart, elevating the
      chin, using a head rest that is sufficiently firm, maximizing anesthesia care
      team access and minimizing fire risk, and taping the patient's head to the
      operating table to reduce unexpected movement with intraocular injury.

PMID- 28759490
TI  - The Expected Role of the Anesthesiologist in Delivering Bad News.

PMID- 28759487
TI  - Aortocaval Compression Syndrome: Time to Revisit Certain Dogmas.
AB  - More than 70 years ago, the phenomenon of "postural shock" in the supine position
      was described in healthy women in late pregnancy. Since then, avoidance of the
      supine position has become a key component of clinical practice. Indeed,
      performing pelvic tilt in mothers at term to avoid aortocaval compression is a
      universally adopted measure, particularly during cesarean delivery. The studies
      on which this practice is based are largely nonrandomized, utilized a mix of
      anesthetic techniques, and were conducted decades ago in the setting of avoidance
      of vasopressors. Recent evidence is beginning to refine our understanding of the
      physiologic consequences of aortocaval compression in the context of contemporary
      clinical practice. For example, magnetic resonance imaging of women at term in
      the supine and tilted positions has challenged the dogma that 15 degrees  of left
      tilt is sufficient to relieve inferior vena cava compression. A clinical
      investigation of healthy term women undergoing elective cesarean delivery with
      spinal anesthesia found no difference in neonatal acid-base status between women
      randomized to be either tilted to the left by 15 degrees  or to be in the supine
      position, if maternal systolic blood pressure is maintained at baseline with a
      crystalloid coload and prophylactic phenylephrine infusion. This review presents
      a fresh look at the decades of evidence surrounding this topic and proposes a
      reevaluation and appraisal of current guidelines regarding entrenched practices.

PMID- 28759491
TI  - The Evaluation of a Noninvasive Respiratory Volume Monitor in Pediatric Patients
      Undergoing General Anesthesia.
AB  - BACKGROUND: Pediatric patients following surgery are at risk for respiratory
      compromise such as hypoventilation and hypoxemia depending on their age,
      comorbidities, and type of surgery. Quantitative measurement of ventilation in
      nonintubated infants/children is a difficult and inexact undertaking. Current
      respiratory assessment in nonintubated patients relies on oximetry data,
      respiratory rate (RR) monitors, and subjective clinical assessment, but there is
      no objective measure of respiratory parameters that could be utilized to predict
      early respiratory compromise. New advances in technology and digital signal
      processing have led to the development of an impedance-based respiratory volume
      monitor (RVM, ExSpiron, Respiratory Motion, Inc, Waltham, MA). The RVM has been
      shown to provide accurate real-time, continuous, noninvasive measurements of
      tidal volume (TV), minute ventilation (MV), and RR in adult patients.In this
      prospective observational study, our primary aim was to determine whether the RVM
      accurately measures TV, RR, and MV in pediatric patients. METHODS: A total of 72
      pediatric patients (27 females, 45 males), ASA I to III, undergoing general
      anesthesia with endotracheal intubation were enrolled. After endotracheal
      intubation, continuous data of MV, TV, and RR were recorded from the RVM and an
      in-line monitoring spirometer (NM3 monitor, Phillips Healthcare). RVM and NM3
      measurements of MV, TV, and RR were compared during a 10-minute period prior to
      the incision ("Presurgery") and a 10-minute period after the end of surgery
      ("Postsurgery"). Relative errors were calculated over 1-minute segment within
      each 10-minute period. Bias, precision, and accuracy were calculated using Bland
      Altman analyses and paired-difference equivalence tests were performed. RESULTS:
      Combined across the Presurgery and Postsurgery periods, the RVM's mean
      measurement bias (RVM - NM3 measurement) for MV was -3.8% (95% limits of
      agreement) (+/-1.96 SD): (-19.9% to 12.2%), for TV it was -4.9 (-21.0% to 11.3%),
      and for RR it was 1.1% (-4.1% to 6.2%). The mean measurement accuracies for MV,
      TV, and RR were 11.9%, 12.0%, and 4.2% (0.6 breaths/min), respectively. Note that
      lower accuracy numbers correspond to more accurate RVM measurements. The
      equivalence tests rejected the null hypothesis that the RVM and NM3 have
      different mean values and conclude with 90% power that the measurements of MV,
      TV, and RR from the RVM and NM3 are equivalent within +/-10%. CONCLUSIONS: Our
      data indicate acceptable agreement between RVM and NM3 measurements in pediatric
      mechanically-ventilated patients. Future studies assessing the capability of the
      RVM to detect respiratory compromise in other clinical settings are needed.

PMID- 28759492
TI  - Chronic Hiccups: An Underestimated Problem.
AB  - Persistent singultus, hiccupping that lasts for longer than 48 hours, can have a
      tremendous impact on a patient's quality of life. Although involved neurologic
      structures have been identified, the function of hiccups remains unclear-they
      have been controversially interpreted as a primitive reflex preventing extent
      swallowing of amniotic fluid in utero, an archaic gill ventilation pattern, or a
      fetus' preparation for independent breathing. Persistent singultus often presents
      as a symptom for various diseases, most commonly illnesses of the central nervous
      system or gastrointestinal tract; they can also be evoked by a variety of
      pharmacological agents. It is often impossible to define a singular cause. A wide
      range of treatment attempts, pharmacological and nonpharmacological, have been
      concerted to this date; however, chlorpromazine remains the only Food and Drug
      Administration-approved drug in this context. Large-scale studies on efficacy and
      tolerance of other therapeutic strategies are lacking. Gabapentin, baclofen, and
      metoclopramide have been reported to accomplish promising results in reports on
      the therapy of persistent singultus; they may also be effective when given in
      combination with other drugs, eg, proton pump inhibitors, or as conjoined
      therapy. As another approach of note, acupuncture treatment was able to abolish
      hiccups in a number of studies. When managing hiccup patients within the clinical
      routine, it is of importance to conduct a comprehensive and effective diagnostic
      workup; a well-functioning interdisciplinary team is needed to address possible
      causes for the symptom. Persistent singultus is a medical problem not to be
      underestimated; more research on options for effective treatment would be greatly
      needed.

PMID- 28759485
TI  - Targeting Hypoxia Signaling for Perioperative Organ Injury.
AB  - Perioperative organ injury has a significant impact on surgical outcomes and
      presents a leading cause of death in the United States. Recent research has
      pointed out an important role of hypoxia signaling in the protection from organ
      injury, including for example myocardial infarction, acute respiratory distress
      syndrome, acute kidney, or gut injury. Hypoxia induces the stabilization of
      hypoxia-inducible factors (HIFs), thereby leading to the induction of HIF target
      genes, which facilitates adaptive responses to low oxygen. In this review, we
      focus on current therapeutic strategies targeting hypoxia signaling in various
      organ injury models and emphasize potential clinical approaches to integrate
      these findings into the care of surgical patients. Conceptually, there are 2
      options to target the HIF pathway for organ protection. First, drugs became
      recently available that promote the stabilization of HIFs, most prominently via
      inhibition of prolyl hydroxylase. These compounds are currently trialed in
      patients, for example, for anemia treatment or prevention of ischemia and
      reperfusion injury. Second, HIF target genes (such as adenosine receptors) could
      be activated directly. We hope that some of these approaches may lead to novel
      pharmacologic strategies to prevent or treat organ injury in surgical patients.

PMID- 28759493
TI  - Degenerative Severe Aortic Stenosis in Tetralogy of Fallot: Multimodality
      Echocardiographic Hemodynamic Assessment.

PMID- 28759494
TI  - Limits of Agreement With Confidence Intervals Are Necessary to Assess
      Comparability of Measurement Devices.

PMID- 28759495
TI  - Trauma Anesthesiology as Part of the Core Anesthesiology Residency Program
      Training: Expert Opinion of the American Society of Anesthesiologists Committee
      on Trauma and Emergency Preparedness (ASA COTEP).

PMID- 28759496
TI  - Addition of Nasal Cannula Can Either Impair or Enhance Preoxygenation With a Bag
      Valve Mask: A Randomized Crossover Design Study Comparing Oxygen Flow Rates.
AB  - BACKGROUND: A critical safety component of emergency anesthesia is the avoidance
      of hypoxemia during the apneic phase of a rapid sequence intubation.
      Preoxygenation with a bag valve mask (BVM) or anesthetic circuit may be improved
      with supplemental oxygen by nasal cannula (NC) if there is a mask leak. In
      addition, NC is recommended for apneic oxygenation after induction and may be
      placed before preoxygenation. However, the optimum NC flow rate for
      preoxygenation or whether the presence of NC alone creates a mask leak remains
      unclear. METHODS: We performed a randomized crossover study on healthy volunteers
      comparing BVM alone and BVM with NC flow rates of 0 (NC-0), 5 (NC-5), 10 (NC-10),
      and 15 (NC-15) liters per minute (lpm). Our primary outcome was end-tidal oxygen
      (ETO2) after 3-minute preoxygenation. RESULTS: There was no difference in ETO2
      between NC-15, NC-10, or BVM-only at 3 minutes. NC-0 and NC-5 recorded
      significantly lower ETO2 at all times compared with NC-15, NC-10, or BVM-only
      (least difference NC-5, -7% [95% confidence interval {CI}, -4% to -10%), NC-0,
      16% [95% CI, 13%-19%]). There was a difference in ETO2 between NC-15 and BVM-only
      at 1 minute (7%; 95% CI, 5%-9%), but not at 2 or 3 minutes. There was no
      difference in ETO2 between NC-10 and NC-15. CONCLUSIONS: Our study found that NC
      at 0 and 5 lpm with a BVM is deleterious to preoxygenation and should be avoided.
      In addition, a lack of difference between NC-10 and BVM-only demonstrates that NC
      at flows of at least 10 lpm should not impair the preoxygenation process. While
      NC-15 may offer a benefit by reaching maximal ETO2 at 1 minute, this would need
      to be balanced against patient comfort.

PMID- 28759497
TI  - Questionable Design to Validate the ProAQT/Pulsioflex Device.

PMID- 28759499
TI  - Corticosteroid Therapy in Nonarteritic Anterior Ischemic Optic Neuropathy.

PMID- 28759500
TI  - Corticosteroid Therapy in Nonarteritic Anterior Ischemic Optic Neuropathy:
      Response.

PMID- 28759501
TI  - Ultrasound-Guided Regional Anesthesia Simulation Training: A Systematic Review.
AB  - BACKGROUND AND OBJECTIVES: Ultrasound-guided regional anesthesia (UGRA) has
      become the criterion standard of regional anesthesia practice. Ultrasound-guided
      regional anesthesia teaching programs often use simulation, and guidelines have
      been published to help guide URGA education. This systematic review aimed to
      examine the effectiveness of simulation-based education for the acquisition and
      maintenance of competence in UGRA. METHODS: Studies identified in MEDLINE,
      EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ERIC were
      included if they assessed simulation-based UGRA teaching with outcomes measured
      at Kirkpatrick level 2 (knowledge and skills), 3 (transfer of learning to the
      workplace), or 4 (patient outcomes). Two authors independently reviewed all
      identified references for eligibility, abstracted data, and appraised quality.
      RESULTS: After screening 176 citations and 45 full-text articles, 12 studies were
      included. Simulation-enhanced training improved knowledge acquisition
      (Kirkpatrick level 2) when compared with nonsimulation training. Seven studies
      measuring skill acquisition (Kirkpatrick level 2) found that simulation-enhanced
      UGRA training was significantly more effective than alternative teaching methods
      or no intervention. One study measuring transfer of learning into the clinical
      setting (Kirkpatrick level 3) found no difference between simulation-enhanced
      UGRA training and non-simulation-based training. However, this study was
      discontinued early because of technical challenges. Two studies examined patient
      outcomes (Kirkpatrick level 4), and one of these found that simulation-based UGRA
      training improved patient outcomes compared with didactic teaching. CONCLUSIONS:
      Ultrasound-guided regional anesthesia knowledge and skills significantly improved
      with simulation training. The acquired UGRA skills may be transferred to the
      clinical setting; however, further studies are required to confirm these changes
      translate to improved patient outcomes.

PMID- 28759503
TI  - Nursing and midwifery use, perceptions and barriers to evidence-based practice: a
      cross-sectional survey.
AB  - AIM: The study aimed to explore how nurses and midwives obtain, use and embed
      evidence in everyday practice. METHODS: The study design was cross-sectional
      survey method. The setting was one local health district in metropolitan Sydney,
      Australia. All nurses and midwives working within the local health district, with
      access to an email account, were invited to participate in the study. An online
      survey questionnaire was distributed to explore how evidence is obtained, used
      and embedded within the clinical setting. The data were analysed using
      descriptive statistics (frequency and percentages). Pearson's Chi-square tests
      were used for comparison between groups. RESULTS: There were 204 survey
      respondents. The findings identified that the majority (n = 157; 76.96%) of
      respondents obtained evidence primarily from clinical practice guidelines. The
      majority (n = 149; 73.04%) of respondents reportedly searched databases and used
      evidence related to general clinical practice. There was a statistical difference
      (chi = 17.069; df = 8; P = 0.029) when comparing leadership positions and other
      registered practitioner groups in the frequency of searching for evidence. Most
      respondents (n = 138; 67.65%) were confident in their ability to change practice
      on the basis of available evidence. Thematic analysis identified four barriers to
      sustaining evidence-based practice, which included: the need for time; the need
      for organizational and management support; the need for educational opportunities
      and challenges to accessing evidence. CONCLUSION: The study provided an
      understanding of how nurses and midwives obtain, use and embed evidence into
      everyday practice. More importantly, the role of leadership is significant to
      support a process of knowledge generation, research translation and the
      implementation of evidence into clinical settings.

PMID- 28759504
TI  - "Relationships, Relationships, Relationships": Promoting Population Health
      Collaboration Across State Government.

PMID- 28759502
TI  - Quadratus Lumborum Block Versus Transversus Abdominis Plane Block in Children
      Undergoing Low Abdominal Surgery: A Randomized Controlled Trial.
AB  - BACKGROUND AND OBJECTIVES: Truncal blocks have a place within multimodal
      analgesia techniques in abdominal surgery. The quadratus lumborum block is a new
      abdominal truncal block used for somatic analgesia of both the upper and lower
      abdomen. In this prospective, double-blind, randomized study, we aimed to compare
      quadratus lumborum block and transversus abdominis plane block in pediatric
      patients undergoing lower abdominal surgery. METHODS: Fifty-three children
      undergoing unilateral inguinal hernia repair or orchiopexy surgery were
      randomized into 2 groups: transversus abdominis plane block and quadratus
      lumborum block. All blocks were performed under general anesthesia before
      surgery. Pain levels were assessed using an FLACC (Face, Legs, Activity, Cry,
      Consolability) scale. RESULTS: The study included 50 patients, after excluding 3
      patients who were not eligible. The number of patients who required analgesia in
      the first 24 hours postoperatively was significantly lower in the quadratus
      lumborum block group (P < 0.05). In the quadratus lumborum block group, the
      postoperative 30-minute and 1-, 2-, 4-, 6-, 12-, and 24-hour FLACC scores were
      lower compared with those of the transversus abdominis plane block group (P <
      0.05). Parent satisfaction scores were higher in the quadratus lumborum block
      group (P < 0.05). CONCLUSIONS: The results of this study showed that in pediatric
      patients undergoing unilateral inguinal hernia repair or orchiopexy the quadratus
      lumborum block provided longer and more effective postoperative analgesia
      compared with the transversus abdominis plane block. CLINICAL TRIALS
      REGISTRATION: The trial was registered prospectively at clinicaltrials.gov
      (NCT02715999).

PMID- 28759506
TI  - Bringing Evidence to the Stretcher Side.

PMID- 28759507
TI  - Prevalence of Pulmonary Embolism in Patients Presenting to the Emergency
      Department for Syncope.
AB  - The Research to Practice column is intended to improve the research critique
      skills of the advanced practice registered nurse and the emergency nurse (RN) and
      to assist with the translation of research into practice. For each column, a
      topic and a research study are selected. The research article is then reviewed
      and critiqued, and the findings are discussed in relation to a patient scenario.
      In this column, we examine the findings of P. from their article, titled
      "Prevalence of Pulmonary Embolism Among Patients Hospitalized for Syncope."

PMID- 28759508
TI  - Metatarsal Stress Fractures.
AB  - Metatarsal stress fractures are also called "march fractures" or "marcher's
      foot." They most commonly occur in the distal second and third metatarsals. The
      second and third metatarsals receive the majority of stress during ambulation and
      are less mobile compared with the other metatarsals. The predominant risk factor
      is excessive overuse with repetitive motions with little recovery time such as
      marching activities in the military. Any element that has a detrimental effect on
      bone density can predispose an individual to stress fractures. There is often a
      delay of 2 or more weeks from the onset of symptoms until visible fractures are
      able to be seen on radiographs. Initial treatment strategies involve rest, ice,
      nonweight bearing, and avoidance of exercise to prevent fracture displacement,
      nonunion, and other complications. Orthopedic referral will guide definitive
      care.

PMID- 28759505
TI  - Qualitative Hormonal Profiling of the Lacrimal Drainage System: Potential
      Insights into the Etiopathogenesis of Primary Acquired Nasolacrimal Duct
      Obstruction.
AB  - PURPOSE: To investigate the presence and distribution patterns of hormone
      receptors in the lacrimal drainage system in normal and diseased states. METHODS:
      The study was performed on cadaveric and clinical samples of the lacrimal
      drainage system. Immunohistochemical labeling was performed for assessing the
      presence and distribution of receptors of estrogen alpha, estrogen beta,
      aromatase (CYP19), testosterone, progesterone, oxytocin, prolactin, and
      somatostatins 1 to 5 (SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5). The
      immunohistochemistry stains were scored as positive or negative, and the
      distribution patterns in the canaliculus, lacrimal sac, and nasolacrimal duct
      were assessed. RESULTS: There was a strong expression of estrogen alpha, estrogen
      beta, and oxytocin, but this showed variations in distribution patterns.
      Testosterone and progesterone expressions were more localized to the basement
      membrane of the epithelium in postmenopausal females. While SSTR2 and SSTR4
      expressed only on the villus surfaces of superficial epithelial cells; oxytocin,
      aromatase, and prolactin additionally expressed in the subepithelial lamina
      propria and submucosal glands. Diseased samples from primary acquired
      nasolacrimal duct obstruction showed dramatic reduction or absence of the
      receptor expression patterns of all the hormones with the exception of epithelial
      immunoreactivity with prolactin. CONCLUSIONS: This study provides a proof of
      principle for the presence of multiple hormone receptors and hypothesizes their
      possible links in the etiopathogenesis of primary acquired nasolacrimal duct
      obstructions.

PMID- 28759509
TI  - Update on Sepsis Treatment in the Emergency Department.
AB  - Sepsis continues to be a devastating, costly, and challenging syndrome to manage
      in emergency departments (ED) across the nation, and its impact seems to be only
      increasing. Recently, consensus recommendations have made some profound changes
      in the way we approach, classify, and treat sepsis. The ED serves as an important
      initial screening and intervention point for sepsis, and ED care can have a
      profound impact on overall morbidity and mortality. The provision of early fluid
      resuscitation, antimicrobial therapy, and vasopressor therapy, if appropriate, is
      essential in early care. The intent of this review was to compare and contrast
      changes associated with the management of sepsis in the ED, with particular focus
      on guideline recommendations for pharmacotherapeutic management.

PMID- 28759510
TI  - Cerebellar Stroke: A Missed Diagnosis.
AB  - Cerebellar strokes account for less than 10% of all strokes but lead to
      significantly poor outcomes. Cerebellar strokes that are initially missed have a
      mortality rate of 40%, and half of the patients who survive have long-term
      deficits. The patient's history may provide clues that point to a cerebellar
      stroke. Signs and symptoms include vertigo, headache, vomiting and ataxia. It is
      important to note the presence of stroke risk factors, such as a history of
      strokes or transient ischemic attacks, diabetes mellitus, hypertension,
      hypercholesterolemia, advanced age, atrial fibrillation, and cigarette smoking.
      The importance of early and correct diagnosis is imperative to reduce morbidity
      and mortality.

PMID- 28759511
TI  - Chemical Burns of the Eye.
AB  - Chemical burns of the eye are one of the most common eye injuries. The extent of
      the ocular surface damage is influenced by the type, temperature, volume, and pH
      of the corrosive substance and duration of exposure. Limbal ischemia found on eye
      assessment is the primary determinant of eventual visual outcome. Eye irrigation
      must be instituted immediately at the scene of exposure and continued in the
      emergency department to reduce visual impairment. Traditionally lactated Ringer's
      and normal saline have been used as irrigation fluids, although one systematic
      review demonstrates similar outcomes with other irrigation fluids. The Morgan
      Lens is a device that can be utilized to allow the provider to perform "hands
      free" eye irrigation. Complications of chemical burns are more common with alkali
      burns as these substances destroy the corneal epithelium and allow this corrosive
      base substance to penetrate deeper into the cornea.

PMID- 28759512
TI  - Implementing Interprofessional Alcohol Screening, Brief Intervention, and
      Referral to Treatment in the Emergency Department: An Evidence-Based Quality
      Improvement Initiative.
AB  - Alcohol misuse is one of the leading causes of illness, disease, injury, and
      death in the Unites States. For many patients, the emergency department (ED)
      visit may provide the only therapeutic opportunity to influence problematic
      drinking behavior. Screening, brief intervention, and referral to treatment
      (SBIRT) is an evidence-based approach that may reduce alcohol-related morbidity
      and mortality and improve health outcomes and quality of life. Developing and
      implementing an alcohol SBIRT educational module for ED nurses and social workers
      is an efficient and effective mechanism to provide education about alcohol SBIRT,
      and revising the electronic health record to include an alcohol SBIRT protocol
      provides a standard mechanism for documentation by the interprofessional team of
      ED nurses and social workers. By integrating SBIRT knowledge as standard of
      practice in the ED setting, providers can positively impact the health and well
      being of patients.

PMID- 28759513
TI  - Importance of Early Detection and Cardiovascular Surgical Intervention in Marfan
      Syndrome.
AB  - Marfan syndrome is an autosomal dominant connective tissue disorder that affects
      multiple systems, including the skeletal, ligamentous, oculofacial, pulmonary,
      abdominal, neurological, and cardiovascular systems. Cardiovascular
      complications, which involve the aorta and aortic valve, contribute most
      significantly to patient morbidity and mortality. A literature review was
      conducted on pathophysiology of the disease and recommendations for early
      diagnosis and treatment. Diagnosis largely relies on clinical features and a
      thorough history. Echocardiogram is used for monitoring aortic abnormalities and
      disease progression. Aortic valve-sparing surgery is indicated in any valvular
      abnormality and in patients with a murmur. Aortic root replacement is indicated
      prophylactically in women who want to give birth with diameters greater than 40
      mm, anyone with a diameter greater than 50 mm, and progressive dilatation of
      greater than 5 mm per year. Medical management involves antihypertensive therapy.
      It is imperative for all health care providers to understand the clinical
      features, progression, and management of Marfan syndrome to appropriately care
      for their patients. Ensuring regular follow-up and adherence to medical and
      surgical prophylaxis is essential to patient well-being.

PMID- 28759515
TI  - Importance of Early Detection and Cardiovascular Surgical Intervention in Marfan
      Syndrome.

PMID- 28759514
TI  - Postgraduate Emergency Nurse Practitioner Fellowships: Opportunities for
      Specialty Education.
AB  - Specialty trained emergency nurse practitioners (ENPs) can meet the demands of an
      unpredictable emergency care environment within an overburdened health care
      system. Although existing literature supports fellowship training as a method for
      bridging academic knowledge with clinical experiences for the novice nurse
      practitioner, the currently available emergency care postgraduate fellowship
      programs are inconsistent in approach. Building upon descriptive data provided by
      the existing 9 postgraduate ENP fellowship programs, a comparison and gap
      analysis of program content was conducted to identify perceived standards for ENP
      specialty education and the congruence with published ENP competencies. Standards
      to curricula, didactics, clinical rotations, and measures of competency were
      identified in the currently established ENP fellowships. A national ENP
      fellowship curriculum has the potential to afford consistency among programs,
      support attainment of competency, and provide clarity to the role and general
      education of advanced practice registered nurses seeking employment in emergency
      care.

PMID- 28759516
TI  - Swedish Children's Lived Experience of Ulcerative Colitis.
AB  - Inflammatory bowel disease (IBD) is increasing in children. When this lifelong
      illness is diagnosed in childhood, especially during adolescence, it may have a
      negative impact on children's quality of life. The aim of the present study was
      to illuminate the meaning of children's lived experience of ulcerative colitis.
      Seven children aged between 10 and 18 years were recruited from University
      Hospital South Sweden and interviewed about the phenomenon under scrutiny. Data
      were analyzed by means of a phenomenological hermeneutical method. The meaning of
      the children's lived experience of ulcerative colitis was summed up as a main
      theme. A daily struggle to adapt and be perceived as normal consisted of 4
      subthemes: being healthy despite the symptoms, being healthy despite being
      afraid, being healthy despite a sense of being different, and being healthy
      despite needing support. The children strove to perceive themselves as healthy,
      and they needed to be perceived as healthy, especially when experiencing symptoms
      of inflammatory bowel disease. Children with inflammatory bowel disease confront
      various problems, such as ambitions and goals that are hard to achieve, due to
      reduced abilities as a result of the illness or an insufficiently adapted
      environment.

PMID- 28759517
TI  - Overt Hepatic Encephalopathy Experienced by Individuals With Cirrhosis: A
      Qualitative Interview Study.
AB  - Hepatic encephalopathy (HE) markedly reduces an individual's quality of life as
      measured by established scoring systems. However, the experiences of having HE
      that can be assumed to cause the loss of quality of life have not yet been
      examined. This study aimed to explore how individuals with cirrhosis experienced
      overt HE by means of an in-depth interview with a tailored semistructured
      interview guide and qualitative analysis. Eight patients with cirrhosis who had
      clinically recovered from disorientation, somnolence, and stupor due to episodic
      HE Grade II or III were interviewed. The collected data were analyzed using
      systematic text condensation, as described by K. . The analysis process
      identified 4 themes, "multiple losses," "anxiety," "dependence on others," and
      "social isolation," which described the experiences of HE both during an episode
      and in recovery. We believe that these findings provide an important contribution
      to gain a deeper understanding of the widespread loss of quality of life caused
      by HE. Management of these individuals should involve procedures and attitudes
      targeted against the described experiences. However, more research is needed
      about the individuals' experiences of HE to further detail such efforts.

PMID- 28759519
TI  - 18F-FDG PET/CT Findings Following Repeated Intramuscular Injections of "Site
      Enhancement Oil" in the Upper Extremities.
AB  - We present the findings on F-FDG PET/CT in a 50-year-old man known to self
      administer intramuscular injections with site enhancement oil in the upper
      extremities. PET images show diffuse pathological high FDG uptake in soft tissue
      of the upper arms and in scanned portions of the forearms. On the CT images, the
      muscles in the upper arm are swollen with a moth-eaten appearance and surrounding
      edema. Interspersed in the muscle tissue are several "cystic" lesions interpreted
      as oil deposits termed oleomas.

PMID- 28759518
TI  - Assessment of Organ Dosimetry for Planning Repeat Treatments of High-Dose 131I
      MIBG Therapy: 123I-MIBG Versus Posttherapy 131I-MIBG Imaging.
AB  - PURPOSE: To evaluate detailed organ-based radiation-absorbed dose for planning
      double high-dose treatment with I-MIBG. METHODS: In a prospective study, 33
      patients with high-risk refractory or recurrent neuroblastoma were treated with
      high-dose I-MIBG. Organ dosimetry was estimated from the first I-MIBG posttherapy
      imaging and from subsequent I-MIBG imaging prior to the planned second
      administration. Three serial whole-body scans were performed per patient 2 to 6
      days after I-MIBG therapy (666 MBq/kg or 18 mCi/kg) and approximately 0.5, 24,
      and 48 hours after the diagnostic I-MIBG dose (370 MBq/kg or 10 mCi/1.73 m).
      Organ radiation doses were calculated using OLINDA. I-MIBG scan dosimetry
      estimations were used to predict doses for the second I-MIBG therapy and compared
      with I-MIBG posttherapy estimates. RESULTS: Mean +/- SD whole-body doses from I
      MIBG and I-MIBG scans were 0.162 +/- 112 and 0.141 +/- 0.068 mGy/MBq,
      respectively. I-MIBG and I-MIBG organ doses were variable-generally higher for I
      MIBG-projected doses than those projected using posttherapy I-MIBG scans. Mean +/
      SD doses to liver, heart wall, and lungs were 0.487 +/- 0.28, 0.225 +/- 0.20,
      and 0.40 +/- 0.26, respectively, for I-MIBG and 0.885 +/- 0.56, 0.618 +/- 0.37,
      and 0.458 +/- 0.56, respectively, for I-MIBG. Mean ratio of I-MIBG to I-MIBG
      estimated radiation dose was 1.81 +/- 1.95 for the liver, 2.75 +/- 1.84 for the
      heart, and 1.13 +/- 0.93 for the lungs. No unexpected toxicities were noted based
      on I-MIBG-projected doses and cumulative dose limits of 30, 20, and 15 Gy to
      liver, kidneys, and lungs, respectively. CONCLUSIONS: For repeat I-MIBG treatment
      planning, both I-MIBG and I-MIBG imaging yielded variable organ doses. However, I
      MIBG-based dosimetry yielded a more conservative estimate of maximum allowable
      activity and would be suitable for planning and limiting organ toxicity with
      repeat high-dose therapies.

PMID- 28759520
TI  - Enhanced Application of 18F-FDG PET/CT in Bladder Cancer by Adding Early Dynamic
      Acquisition to a Standard Delayed PET Protocol.
AB  - PURPOSE: We investigated the value of early dynamic (ED) PET for the detection
      and characterization of bladder cancer. METHODS: Fifty-two bladder cancer
      patients were prospectively enrolled. The study protocol was composed of ED,
      whole-body (WB, 60 minutes after injection), and additional delayed (AD, 120
      minutes after injection) PET acquisition. Early dynamic PET was acquired for 10
      minutes and reconstructed as 5 frames at 2-minute intervals. A focal radiotracer
      accumulation confined to the bladder wall was considered as PET positive and
      referred for further quantitative measurement. SUVmax on ED (SUVmax, SUVmax,
      SUVmax, SUVmax, and SUVmax for 5 frames), WB (SUVmax), and AD PET (SUVmax) were
      measured. PET results were correlated with bladder cancer pathology variables.
      RESULTS: The sensitivities of ED, WB, and AD PET for bladder cancer were 84.6%,
      57.7%, and 61.2%, respectively. The sensitivity of ED PET was significantly
      higher than that of WB (P = 0.002) and AD PET (P = 0.008). On ED PET, SUVmax was
      significantly correlated with muscle invasiveness, histological grade, and
      pathological tumor size (P = 0.018, P = 0.030, and P = 0.030). On WB and AD PET,
      only pathological tumor size showed significant positive correlation with SUVmax
      and SUVmax (P = 0.043 and P = 0.007). CONCLUSIONS: Early dynamic PET can help to
      detect and characterize bladder cancer.

PMID- 28759521
TI  - 68Ga-PSMA Uptake in Neurofibromas Demonstrated on PET/CT in a Patient With
      Neurofibromatosis Type 1.
AB  - We present a case of Ga-PSMA PET/CT imaging of PSMA expression in neurofibromas
      in a patient with neurofibromatosis type 1 (or von Recklinghausen disease). PSMA
      uptake has previously been demonstrated in schwannomas both with PET and
      histological staining. The presented images confirm that PSMA expression in
      cutaneous neurofibromas can be well imaged with PET, with uptake mostly at
      relatively low levels. Interestingly, some lesions demonstrated significantly
      higher PSMA expression, although the clinical significance of these differences
      remains to be determined. The images raise the possibility of a potential role
      for Ga-PSMA PET/CT in neurofibromatosis type 1 monitoring.

PMID- 28759523
TI  - Unusual Presentation of Postradiation Sarcoma With Subsequent Intestinal
      Metastasis Revealed by 18F-FDG PET/CT.
AB  - Radiation-related sarcoma is a rare but serious complication for patients after
      receiving radiation therapy initially for their primary malignancy. However, it
      usually takes several years and needs enough in-field radiation dose to develop
      this sarcoma. We describe a 60-year-old man with right axillary sarcoma revealed
      by whole-body F-FDG PET/CT 1 year after chemoradiotherapy, which presented
      ultrashort latency period and did not match the consensus definition of radiation
      related sarcoma. Besides, metastatic sarcoma to small intestine was accidentally
      noted in the F-FDG PET/CT image.

PMID- 28759524
TI  - Adrenocorticotropic Hormone-Secreting Neuroendocrine Tumor of the Rectum
      Demonstrated on 68Ga-DOTATATE and 18F-FDG PET Imaging.
AB  - An 81-year-old man with Cushing syndrome was referred for a Ga-DOTATATE PET/CT
      study to investigate for an ectopic source of adrenocorticotropic hormone. The
      scan demonstrated mildly increased octreopeptide uptake at a rectal mass and
      focal uptake at multiple regions throughout the bone marrow of the axial
      skeleton, consistent with metastases. A subsequent F-FDG PET/CT study was
      performed for further evaluation and demonstrated markedly increased metabolism
      at the previously identified rectal mass, in addition to the liver and multiple
      regions throughout the skeleton. Histopathology from biopsy of the rectal mass
      confirmed a small cell neuroendocrine carcinoma.

PMID- 28759525
TI  - Ultrasound and PET-CT Correlation in Shoulder Pathology: A 5-Year Retrospective
      Analysis.
AB  - PURPOSE: To correlate shoulder ultrasound and radiography with F-FDG PET-CT to
      establish FDG uptake and therefore range of metabolic activity, as defined by SUV
      analysis, in various symptomatic shoulder pathologies. METHODS: Retrospective
      database query was performed for shoulder ultrasound and PET-CT scans between
      January 2012 and January 2017. Patients who had both studies within 1 year were
      included. Age- and sex-matched control patients with PET-CT scans only were also
      included. Retrospective image review determined shoulder pathology, and F-FDG
      SUVmax was measured using regions of interest placed at the glenohumeral joint,
      rotator cuff/bursa, and bicipital groove. Glenohumeral and acromioclavicular
      osteoarthrosis was assessed by radiography using the Kellgren-Lawrence
      classification system. RESULTS: Thirty-three patients had both imaging studies
      within 1 year. Ten patients (11 cases) were included, ranging in age from 56 to
      90 years (mean, 67.9 years). Control subjects were selected among patients
      receiving PET-CT within 1 week of symptomatic patients. Glenohumeral
      osteoarthrosis was mild in 3 (27%), moderate in 2 (18%), and severe in 2 (18%).
      Six full-thickness rotator cuff tears (55%) were identified. SUVmax means were
      compared between the pathologic and control groups and were significantly higher
      in the former: glenohumeral joint (1.96 vs 1.32; P = 0.016), rotator cuff/bursa
      (2.80 vs 2.0; P = 0.005), and bicipital groove (2.19 vs 1.48; P = 0.007). The
      highest values were seen in full-thickness rotator cuff tear and severe biceps
      tenosynovitis. CONCLUSIONS: Increased metabolic activity about the shoulder is
      associated with a spectrum of rotator cuff, glenohumeral joint, and other soft
      tissue pathology that can be correlated with diagnostic ultrasound findings.

PMID- 28759526
TI  - 68Ga-PSMA Uptake in an Incidentally Detected Gastrointestinal Stromal Tumor in a
      Case of Suspected Carcinoma Prostate.
AB  - A 74-year-old man with suspected prostate cancer and a previously negative
      transrectal ultrasound-guided prostate biopsy underwent Ga-PSMA PET/CT. Scan
      showed no abnormal tracer concentration in enlarged prostate gland to suggest
      prostate cancer. Note was made of an incidentally detected well defined soft
      tissue lesion in the greater curvature of the stomach with moderate tracer
      concentration in its intraluminal portion. Biopsy of the lesion revealed
      gastrointestinal stromal tumor.

PMID- 28759527
TI  - 18F-FDG Uptake in Parsonage-Turner Syndrome.
AB  - A 55-year-old man with large B-cell lymphoma developed atraumatic left shoulder
      pain. F-FDG PET/CT revealed new left supraspinatus and infraspinatus muscle
      uptake while the initial disease resolved. Given the discrepancy between initial
      disease treatment response and new left shoulder findings, an MRI scan was
      performed. This demonstrated diffuse supraspinatus and infraspinatus muscle edema
      and enhancement with no focal lesion. Muscle biopsy was negative for lymphoma,
      but features of muscle denervation were seen. Overall, clinical and imaging
      findings were compatible with Parsonage-Turner syndrome (acute brachial
      neuritis), an uncommon condition that presented as a false-positive finding on
      PET/CT.

PMID- 28759528
TI  - 18F-FDG PET/CT Demonstrating Chorioadenoma Destruens After Evacuation of Complete
      Hydatidiform Mole.
AB  - Gestational trophoblastic neoplasias (GTNs) are a group of pregnancy-related
      neoplasms, which include chorioadenoma destruens (invasive mole), placental site
      trophoblastic tumor, and choriocarcinoma. Although the role of F-FDG PET/CT is
      still undefined in GTN, in selected cases, it can have significant impact on
      patient management. Here, we present the case of a 29-year-old woman with
      hydatidiform mole suggestive of GTN 3 months after evacuation. F-FDG PET/CT
      demonstrated chorioadenoma destruens (invasive mole) and ruled out metastasis in
      this case.

PMID- 28759529
TI  - Quality and Safety in Health Care, Part XXIX: The Transcatheter Valve Therapy
      Registry.
AB  - The American College of Cardiology, the Society of Thoracic Surgeons, and other
      organizations cooperated to form the Transcatheter Valve Therapy Registry. This
      registry studies information on the outcome of valve therapy device placement
      with a transcatheter approach. The companies that manufacture these devices can
      use the registry to meet the post-product sale surveillance requirements of the
      US Food and Drug Administration. There will also be linkage to the registry
      information from the Society of Thoracic Surgeons Adult Cardiac Surgery Database,
      which has information on open cardiac valve surgery.

PMID- 28759530
TI  - Sevoflurane attenuates systemic inflammation compared with propofol, but does not
      modulate neuro-inflammation: A laboratory rat study.
AB  - BACKGROUND: Septic encephalopathy is believed to be a result of neuro
      inflammation possibly triggered by endotoxins, such as lipopolysaccharides (LPS).
      Modulation of the immune system is a property of volatile anaesthetics.
      OBJECTIVE: We aimed to investigate the systemic and cerebral inflammatory
      response in a LPS-induced sepsis model in rats. We compared two different
      sedation strategies, intravenous propofol and the volatile anaesthetic
      sevoflurane, with the hypothesis that the latter may attenuate neuro-inflammatory
      processes. DESIGN: Laboratory rat study. SETTING: Basic research laboratories at
      the University Hospital Zurich and University Zurich Irchel between August 2014
      and June 2016. PATIENTS: A total of 32 adult male Wistar rats. INTERVENTIONS:
      After tracheotomy and mechanical ventilation, the anaesthetised rats were
      monitored before sepsis was induced by using intravenous LPS or phosphate
      buffered saline as control. Rats were sedated with propofol (10 mg kg h) or
      sevoflurane (2 vol%) continuously for 12 h. MAIN OUTCOME MEASURES: Systemic
      inflammatory markers such as cytokine-induced neutrophil chemo-attractant protein
      1, monocyte chemo-tactic protein-1 and IL-6 were determined. The same cytokines
      were measured in brain tissue. Cellular response in the brain was assessed by
      defining neutrophil accumulation with myeloperoxidase and also activation of
      microglia with ionised calcium-binding adaptor molecule-1 and astrocytes with
      glial fibrillary acidic protein. Finally, brain injury was determined. RESULTS:
      Animals were haemodynamically stable in both sedation groups treated with LPS.
      Blood cytokine peak values were lower in the sevoflurane-LPS compared with
      propofol-LPS animals. In brain tissue of LPS animals, chemoattractant protein-1
      was the only significantly increased cytokine (P = 0.003), however with no
      significance between propofol and sevoflurane. After LPS challenge, cerebral
      accumulation of neutrophils was observed. Microglia activation was pronounced in
      the hippocampus of animals treated with LPS (P = 0.006). LPS induced prominent
      astrogliosis (P < 0.001). There was no significant difference in microglia or
      astrocyte activation or apoptosis in the brain between sevoflurane and propofol.
      CONCLUSION: We have shown that systemic attenuation of inflammation by the
      volatile anaesthetic sevoflurane did not translate into attenuated neuro
      inflammation in this LPS-induced inflammation model. TRIAL REGISTRATION: Animal
      approval No. 134/2014, Veterinaramt Zurich.

PMID- 28759531
TI  - Sexual Offender Treatment Readiness, Responsivity, and Change: Linkages to
      Treatment Completion and Recidivism.
AB  - This study examined the interrelationship of treatment readiness, responsivity
      variables, and treatment change to sexual offender treatment outcome, featuring
      the Treatment Readiness, Responsivity, and Gain Scale: Short Version (TRRG:SV).
      The sample was composed of 185 Canadian federal offenders who attended a high
      intensity sexual offender treatment program and were followed up an average of
      9.3 years postrelease. Men with higher levels of education, employment history,
      and cognitive ability and who were married or equivalent, did not have a serious
      mental illness or intellectual disability, and were not actuarially high risk
      tended to show higher levels of treatment engagement across the TRRG:SV
      subscales. Significant pre-post changes, denoting improvement, were observed on
      the TRRG:SV. In turn, positive treatment engagement assessed by the TRRG:SV was
      associated with increased risk-relevant treatment change, decreased program
      attrition, and reductions in sexual and violent recidivism, even after
      controlling for baseline risk. The role of attention to responsivity variables
      and treatment readiness to promote client engagement and maximize therapeutic
      benefit is underscored.

PMID- 28759532
TI  - Wrist Resistance Training Improves Motor Control and Strength.
AB  - Chu, E, Kim, Y-S, Hill, G, Kim, YH, Kim, CK, and Shim, JK. Wrist resistance
      training improves motor control and strength. J Strength Cond Res 32(4): 962-969,
      2018-The aim of this study was to investigate the effects of a 6-week direction
      specific resistance training program on isometric torque control and isokinetic
      torque strength of the wrist joint. Nineteen subjects were randomly assigned to
      either the wrist training group (n = 9) or the control group (n = 10). The
      training group performed wrist exercises in 6 directions (flexion, extension,
      pronation, supination, radial deviation, and ulnar deviation), whereas the
      control group did not. Data were collected on the isometric torque control, 1
      repetition maximum (1RM) strength, and isokinetic maximum torque (angular
      velocity of 60 degrees  per second wrist movements) before and after 6 weeks of
      resistance training and at 2-week intervals during training. The training group
      showed significant decreases in isometric torque control error in all 6
      directions after 2 weeks of resistance training, whereas the control group did
      not show significant increase or decrease. After 4 weeks of training, the
      training group showed significant increases in maximum strength in all 6
      directions as assessed by 1RM strength and isokinetic strength tests, whereas the
      control group did not show any statistically significant changes. This study
      shows that motor control significantly improves within the first 2 weeks of
      resistance training, whereas the wrist strength significantly improves within the
      first 4 weeks of resistance training. Based on the findings of this study,
      coaches and trainers should consider wrist resistance training to improve
      athletes' muscular strength and control of the wrist muscles.

PMID- 28759533
TI  - Physiological Responses to and Athlete and Coach Perceptions of Exertion During
      Small-Sided Basketball Games.
AB  - Vaquera, A, Suarez-Iglesias, D, Guiu, X, Barroso, R, Thomas, G, and Renfree, A.
      Physiological responses to and athlete and coach perceptions of exertion during
      small-sided basketball games. J Strength Cond Res 32(10): 2949-2953, 2018-This
      study describes heart rate (HR) responses during different small-sided games
      (SSGs) in junior basketball players and identifies the level of agreement between
      athlete and coach perceptions of internal training load calculated using the in
      task rating of perceived exertion (RPE) method. Over a 6-week period, 12 male
      junior basketball players, who played in the Spanish national under-18 League,
      played 7 games of one-a-side (1v1), 6 games of 2-a-side (2v2), 8 games of 5-a
      side (5v5), and 5 games of superiority (3v2) situations. During 1v1, 2v2, 5v5,
      and 3v2, peak HRs were 90.27 +/- 3.37%, 92.68 +/- 3.29%, 92.01 +/- 3.48%, and
      88.74 +/- 5.77% of HRmax, respectively. These differences were statistically
      significant between 1v1 and 2v2 (p < 0.01), 1v1 and 5v5 (p <= 0.05), 2v2 and 3v2
      (p < 0.001), and 5v5 and 3v2 (p < 0.001). Mean HR was 79.5 +/- 4.4%, 83.1 +/-
      4.2%, 91.2 +/- 4.7%, and 78.5 +/- 7.5% of HRmax during 1v1, 2v2, 5v5, and 3v2,
      respectively, and differences were observed between 1v1 and 2v2 (p < 0.001), 2v2
      and 3v2 (p < 0.001), and 5v5 and 3v2 (p <= 0.05). There were differences in
      athletes and coaches in-task RPE in all SSGs (all p < 0.0001 apart from 5 * 5 p =
      0.0019). The 2v2 format elicited a higher mean in-task RPE in comparison with all
      other SSGs (p < 0.001), possibly because 2v2 imposes a greater cognitive load.

PMID- 28759534
TI  - Predicting the intensity for performing supramaximal incline treadmill interval
      training in distance runners.
AB  - Recent evidence highlights the effectiveness of 30-second bouts paired with level
      grade supramaximal interval training (SMIT) and incline treadmill training (INC),
      respectively, in distance runners. While INC has been described as a form of
      SMIT, no investigation of INC involving a supramaximal intensity and 30-second
      bouts has occurred; hence, no established recommendation for prescribing a
      supramaximal intensity with 30-second bouts for INC exists. Therefore, the
      purpose of this investigation included reporting on the time-to-exhaustion (Tmax)
      response and test-retest reliability of running on a 5% grade using supramaximal
      intensities of 110, 115, 120, 125 and 130% of the velocity associated with
      maximum oxygen consumption (Vmax). Additionally, these measures were assessed
      during 140%Vmax and 1% grade. A second aim included determining the %Vmax
      associated with a 30-second effort via bivariate analysis. Twelve distance
      runners (age, 26.9 +/- 4.8 yrs; body mass, 69.2 +/- 11.7 kg; height, 177.3 +/-
      10.2 cm; and VO2max, 61.4 +/- 6.3 ml[BULLET OPERATOR]kg[BULLET OPERATOR]min)
      completed 2 Tmax trials at each intensity for measures of reliability. The
      dependent variable was the Tmax of each condition. Statistical significance was
      set to p < 0.05. Student's t-test revealed no significant differences between
      trials for all intensities. One-way analysis of variance revealed a) Tmax during
      INC at 110%Vmax was significantly different than all conditions except 115%Vmax;
      and b) no significant difference in Tmax between 120, 125, 130 and 140%Vmax
      conditions. In conclusion, Tmax of all conditions proved reliable, and bivariate
      analysis revealed running at 125%Vmax on a 5% grade yielded a 30-second effort.

PMID- 28759535
TI  - Relationship between physical fitness at the end of pre-season and the in-season
      game performance in Japanese female professional baseball players.
AB  - This study examined anthropometric and fitness profiles of Japanese female
      professional baseball players and investigated the relationship between players'
      physical fitness and in-season game performance. Fifty-seven players who were
      registered in the Japan Women's Baseball League (JWBL) participated. Height,
      weight, grip strength, back strength, knee-extension and -flexion strength,
      hamstring extensibility, vertical jump height, and horizontal jump distance were
      measured at pre-season (February and March) in 2013. Game performance during the
      2013 season (March to November) was obtained from official JWBL statistics.
      Vertical jump height showed significant positive correlations with individual
      performance records [e.g., total bases (r = 0.551), slugging percentage (r =
      0.459), and stolen bases (r = 0.442)]. Similar relationships were observed
      between horizontal jump distance and performance statistics in most cases. In
      contrast, grip, back, and lower-limb strength, and hamstring extensibility were
      not significantly correlated with game performance. Stepwise regression analysis
      selected vertical jump height as an independent variable, significantly
      correlating with several game performance measures (e.g., total bases: adjusted R
      = 0.257). Also, vertical jump height and body mass index were identified as
      independent variables significantly associated with stolen bases (adjusted R =
      0.251). Maximal jump performance, rather than simple isometric muscle strength or
      flexibility, is a good performance test that can be used at the end of pre-season
      to predict in-season batting and stolen base performance. Our findings
      demonstrate the importance of constructing pre-season training programs to
      enhance lower-limb muscular power that is linked to successful in-season
      performance in female baseball players.

PMID- 28759536
TI  - Ranking Prediction Model Using the Competition Record of Ladies Professional Golf
      Association Players.
AB  - Chae, JS, Park, J, and So, W-Y. Ranking prediction model using the competition
      record of ladies professional golf association players. J Strength Cond Res
      32(8): 2363-2374, 2018-The purpose of this study was to suggest a ranking
      prediction model using the competition record of the Ladies Professional Golf
      Association (LPGA) players. The top 100 players on the tour money list from the
      2013-2016 US Open were analyzed in this model. Stepwise regression analysis was
      conducted to examine the effect of performance and independent variables (i.e.,
      driving accuracy, green in regulation, putts per round, driving distance,
      percentage of sand saves, par-3 average, par-4 average, par-5 average, birdies
      average, and eagle average) on dependent variables (i.e., scoring average,
      official money, top-10 finishes, winning percentage, and 60-strokes average). The
      following prediction model was suggested:(Equation is included in full-text
      article.)(Equation is included in full-text article.)(Equation is included in
      full-text article.)(Equation is included in full-text article.)(Equation is
      included in full-text article.)Scoring of the above 5 prediction models and the
      prediction of golf ranking in the 2016 Women's Golf Olympic competition in Rio
      revealed a significant correlation between the predicted and real ranking (r =
      0.689, p < 0.001) and between the predicted and the real average score (r =
      0.653, p < 0.001). Our ranking prediction model using LPGA data may help coaches
      and players to identify which players are likely to participate in Olympic and
      World competitions, based on their performance.

PMID- 28759537
TI  - The Effects of Multiple Sets of Squats and Jump Squats on Mechanical Variables.
AB  - PURPOSE: The mechanical responses to two non-ballistic squat and two ballistic
      jump squat protocols performed over multiple sets were investigated. One protocol
      from each of the two non-ballistic and ballistic conditions incorporated a pause
      between the eccentric and concentric phases of the movements in order to
      determine the influence of the coupling time on the mechanical variables and post
      activation potentiation (PAP). METHODS: Eleven men (age: 21.9 +/- 1.8 years;
      height: 1.79 +/- 0.05 m; mass: 87.0 +/- 7.4 kg) attended four sessions where they
      performed multiple sets of squats and jump squats with a load equivalent to 30% 1
      repeititon maximum under one of the following conditions: 1) 3 * 4 repetitions of
      non-ballistic squats (30N-B); 2) 3 * 4 repetitions of non-ballistic squats with a
      3-second pause between the eccentric and concentric phases of each repetition
      (30PN-B); 3) 3 * 4 repetitions of ballistic jump squats (30B); 4) 3 * 4
      repetitions of ballistic jump squats with a 3-second pause between the eccentric
      and concentric phases of each repetition (30PB). Force plates were used to
      calculate variables including average vertical velocity, average vertical force
      (GRF), and average power output (PO). RESULTS: Vertical velocities during the
      ballistic conditions were significantly greater than those attained during the
      non-ballistic conditions (mean differences: 0.21 - 0.25 m/s, p<0.001, effect
      sizes [ES]: 1.70 - 1.89) as were GRFs (mean differences: 478 - 526 N, p<0.001,
      ES: 1.61 - 1.63), and PO (mean differences: 711 - 869 W, p<0.001, ES: 1.66 -
      1.73). Moreover, the increase in PO across the three sets in 30B was
      significantly greater than the changes observed during 30N-B, 30PN-B, and 30PB
      (p<=0.015). The pause reduced the mechanical variables during both the non
      ballistic and ballistic conditions, although the differences were not
      statistically significant (p>0.05). CONCLUSION: Ballistic jump squats may be an
      effective exercise for developing PO given the high velocities and forces
      generated in these exercises. Furthermore, the completion of multiple sets of
      jump squats may induce PAP to enhance PO. The coupling times between the
      eccentric and concentric phases of the jump squats should be short in order to
      maximize the GRF and PO across the sets.

PMID- 28759538
TI  - Validity and reliability of the Hexoskin(r) wearable biometric vest during
      maximal aerobic power testing in elite cyclists.
AB  - The purpose of this study was to investigate the validity and reliability of the
      Hexoskin(r) vest for measuring respiration and heart rate (HR) in elite cyclists
      during a progressive test to exhaustion. Ten male elite cyclists (age 28.8 +/-
      12.5 yr, height 179.3 +/- 6.0 cm, weight 73.2 +/- 9.1 kg, V O2max 60.7 +/- 7.8
      ml.kg.min mean +/- SD) conducted a maximal aerobic cycle ergometer test using a
      ramped protocol (starting at 100W with 25W increments each min to failure) during
      two separate occasions over a 3-4 day period. Compared to the criterion measure
      (Metamax 3B) the Hexoskin(r) vest showed mainly small typical errors (1.3-6.2%)
      for HR and breathing frequency (f), but larger typical errors (9.5-19.6%) for
      minute ventilation (VE) during the progressive test to exhaustion. The typical
      error indicating the reliability of the Hexoskin(r) vest at moderate intensity
      exercise between tests was small for HR (2.6-2.9%) and f (2.5-3.2%) but slightly
      larger for VE (5.3-7.9%). We conclude that the Hexoskin(r) vest is sufficiently
      valid and reliable for measurements of HR and f in elite athletes during high
      intensity cycling but the calculated VE value the Hexoskin(r) vest produces
      during such exercise should be used with caution due to the lower validity and
      reliability of this variable.

PMID- 28759539
TI  - Reliability Characteristics and Applicability of a Repeated Sprint Ability Test
      in Young Male Soccer Players.
AB  - Castagna, C, Lorenzo, F, Krustrup, P, Fernandes-da-Silva, J, Povoas, SCA,
      Bernardini, A, and D'Ottavio, S. Reliability characteristics and applicability of
      a repeated sprint ability test in young male soccer players. J Strength Cond Res
      32(6): 1538-1544, 2018-The aim of this study was to examine the usefulness and
      reliability characteristics of a repeated sprint ability test considering 5 line
      sprints of 30 m interspersed with 30 seconds of active recovery in nonelite,
      outfield, young, male soccer players. Twenty-six (age, 14.9 +/- 1.2 years;
      height, 1.72 +/- 0.12 cm; body mass, 62.2 +/- 5.1 kg) players were tested 48
      hours and 7 days apart for 5 * 30-m performance over 5 trials (T1-T5). Short-term
      (T1-T2) and long-term (T1-T3-T4-T5) reliabilities were assessed with intraclass
      correlation coefficient (ICC) and with typical error for measurement (TEM). Short
      and long-term reliability ICCs and TEMs for total sprint time and best sprint
      performance were nearly perfect and satisfactory, respectively. Usefulness (as
      smallest worthwhile change and TEM ratio) resulted acceptable (i.e., = 1) and
      good (i.e., >1) for total sprint time and best sprint performance, respectively.
      The present study revealed that the 5 * 30-m sprint test is a reliable field test
      in short and long terms when the sum of sprint times and the best sprint
      performance are considered as outcome variables. Sprint performance decrements
      variables showed large variability across trials.

PMID- 28759540
TI  - Comparison of the Technique of the Football Quarterback Pass Between High School
      and University Athletes.
AB  - Toffan, A, Alexander, MJL, and Peeler, J. Comparison of the technique of the
      football quarterback pass between high school and university athletes. J Strength
      Cond Res 32(9): 2474-2497, 2018-The purpose of the study was to compare the most
      effective joint movements, segment velocities, and body positions to perform the
      fastest and most accurate pass of high school and university football
      quarterbacks. Secondary purposes were to develop a quarterback throwing test to
      assess skill level, to determine which kinematic variables were different between
      high school and university athletes, and to determine which variables were
      significant predictors of quarterback throwing test performance. Ten high school
      and 10 university athletes were filmed for the study, performing 9 passes at a
      target and 2 passes for maximum distance. Thirty variables were measured using
      Dartfish Team Pro 4.5.2 video analysis system, and Microsoft Excel was used for
      statistical analyses. University athletes scored slightly higher than the high
      school athletes on the throwing test; however, this result was not statistically
      significant. Correlation analysis and forward stepwise multiple regression
      analysis were performed on both the high school players and the university
      players to determine which variables were significant predictors of throwing test
      score. Ball velocity was determined to have the strongest predictive effect on
      throwing test score (r = 0.900) for the high school athletes; however, position
      of the back foot at release was also determined to be important (r = 0.661) for
      the university group. Several significant differences in throwing technique
      between groups were noted during the pass; however, body position at release
      showed the greatest differences between the 2 groups. High school players could
      benefit from more complete weight transfer and decreased throw time to increase
      throwing test score. University athletes could benefit from increased throw time
      and greater range of motion in external shoulder rotation and trunk rotation to
      increase their throwing test score. Coaches and practitioners will be able to use
      the findings of this research to help improve these and related throwing
      variables in their high school and university quarterbacks.

PMID- 28759541
TI  - Traumatic Ventricular Septal Defect After Stab Wound to the Chest Missed by
      Transthoracic Echocardiography: A Case Report.
AB  - Traumatic ventral septal defect may be sustained after either blunt force or
      penetrating trauma to the chest. Severity ranges from asymptomatic to acute
      decompensated heart failure. Our patient suffered a stab wound to the chest and
      was initially taken to the operating room for repair of a lacerated right
      ventricle. Subsequent postoperative hemodynamic deterioration prompted a bedside
      transthoracic echocardiogram, which failed to identify causal factors. A
      transesophageal echocardiogram performed immediately after ventral septal defect
      was demonstrated. This case serves to highlight the gaps in current standard
      practice and encourages the use of transesophageal echocardiogram as a screening
      tool in patients after penetrating cardiac injuries.

PMID- 28759542
TI  - Video-Assisted Thoracoscopic Versus Robotic-Assisted Thoracoscopic Thymectomy:
      Systematic Review and Meta-analysis.
AB  - OBJECTIVE: Minimally invasive thoracic surgical procedures, performed with or
      without the assistance of a robot, have gained popularity over the last decade.
      They have increasingly become the choice of intervention for a number of thoracic
      surgical operations. Minimally invasive surgery decreases postoperative pain,
      hospital stay and leads to a faster recovery in comparison with conventional open
      methods. Minimally invasive techniques to perform a thymectomy include video
      assisted thoracoscopic surgery (VATS) or robotic-assisted thoracoscopic surgery
      (RATS). In this study, we aim to systematically review and interrogate the
      literature on minimally invasive thymectomy and draw a meta-analysis on the
      outcomes between the two approaches. METHODS: An extensive electronic health
      database search was performed on all articles published from inception to May
      2015 for studies describing outcomes in VATS and RATS thymectomy. RESULTS: A
      total of 350 patients were included in this study, for which 182 and 168 patients
      underwent RATS and VATS thymectomy, respectively. There were no recorded in
      hospital deaths for either procedure. There was no statistical difference in
      conversion to open, length of hospital stay, or postoperative pneumonia.
      Operational times for RATS thymectomy were longer. CONCLUSIONS: The VATS and RATS
      thymectomy offer good and safe operative and perioperative outcomes. There is
      little difference between the two groups. However, there is poor evidence basis
      for the long-term outcomes in minimally invasive procedures for thymectomy. It is
      imperative that future studies evaluate oncological outcomes both short and long
      term as well as those related to safety.

PMID- 28759543
TI  - Endovascular Repair of Peripheral Arterial Disease: Midterm Results From a Single
      Center.
AB  - OBJECTIVE: One thousand consecutive patients who underwent endovascular repair in
      an 8-year period were studied retrospectively to evaluate technical success,
      freedom from reinterventions, early clinical outcome, and risk factors for
      restenosis/occlusion. METHODS: Mean +/- SD Rutherford class was 3.29 +/- 0.8. A
      total of 755 patients have claudication, 423 from rest pain, and 569 from
      ischemic ulceration. RESULTS: A total of 552 men and 448 women (mean +/- SD =
      69.84 +/- 8 years; range = 19-89 years) underwent endovascular repair. A total of
      698 patients received local anesthesia and 302 general anesthesia. A total of 447
      patients received percutaneous transluminal angioplasty, 650 stents were placed;
      231 atherectomies were performed and 171 patients received hybrid approach. The
      procedure was successful in 847 patients (84%). There was no early death. There
      were 151 early occlusions (95 underwent surgery, 56 received stents), 121
      dissections (39 underwent surgery, 56 received stents and 26 medical treatment),
      32 hematoma, and 13 early leaks. Mean +/- SD Rutherford class improved to 3.02 +/
      0.9. Freedom from reintervention rate at 8 years was 76%. A total of 63 patients
      underwent surgery and 59 cellular therapy. A total of 134 finger, 142 below-knee,
      and 29 above-knee amputations were reported. CONCLUSIONS: Endovascular
      interventions can be performed with a satisfactory technical success and low
      complication rates; however, nonfatal complications and catheter-based
      reinterventions are frequent.

PMID- 28759546
TI  - Valid, Reproducible, Clinically Useful, Nonstigmatizing Terminology for the
      Disease and Its Treatment: Addiction, Substance Use Disorder, and Medication.

PMID- 28759544
TI  - Minimally Invasive Access Aortic Arch Surgery.
AB  - OBJECTIVE: Median sternotomy is still the standard approach for aortic arch
      surgery. Minimally invasive techniques promise faster recovery with shorter
      hospital stay due to thoracic stability, reduced pain, and superior cosmetic
      results. However, safety is a concern in complex aortic surgery. The aim of our
      study was to demonstrate that aortic arch surgery via partial upper sternotomy is
      viable, safe, and equivalent to standard procedure both in terms of its safety
      and the risk of major adverse cardiac and cerebrovascular events. METHODS: We
      interrogated our prospectively collected database and identified a total of 21
      nonemergent patients operated on at our center between October 2008 and February
      2015. Indication for operation was aneurysmatic disease in 18 and aortic
      dissection in 3 patients. Data were analyzed for in-hospital mortality, stroke,
      bleeding complications, and acute kidney injury. RESULTS: Mean +/- standard
      deviation age of patients was 69.3 +/- 14.4 years, 57.1% were female, and mean +/
      standard deviation logistic EuroSCORE was 17.0 +/- 7.2%. Surgery on the aortic
      arch comprised proximal arch in 9, hemiarch in 9, and total arch replacement plus
      frozen elephant trunk in 3 patients. Concomitant procedures included aortic root
      repair in 10, aortic root replacement in 2, and aortic valve replacement in 3
      patients. We lost one patient because of septic shock, no stroke occurred, but a
      transient neurologic deficit in three and a postoperative delirium in four
      patients. Re-exploration for bleeding was necessary in two patients, and one
      patient had acute kidney injury. CONCLUSIONS: Minimally invasive aortic arch
      surgery via partial upper sternotomy does not increase the risk of morbidity or
      mortality. Thus, in experienced hands, it is viable, safe, and therefore
      favorable and as a result should be offered to more patients.

PMID- 28759547
TI  - Nonmedical Prescription Opioid Use for the Self-treatment of Pain in Young
      Adults: A National Shame.
AB  - : Evans et al. (2017) have pointed out how frequently and pervasively nonmedical
      prescription opioid use is associated with severe pain in young adults,
      especially young white males. This is a subset of such nonmedical users at
      tremendous risk of overdose (indeed 1/3 of the study respondents had an overdose
      event), especially given their concomitant use of benzodiazepines. Avoiding
      further contributing to the catastrophic rise in overdoses requires access to
      comprehensive pain care for these young adults. If they were to require opioid
      therapy, it would have to be in the context of a highly complex and expert
      variety of such care. If we fail to make it available, we will fail to address
      the root cause of overdoses for a sizeable subset of nonmedical prescription
      opioid users.

PMID- 28759548
TI  - Addiction is More Than a Substance Use Disorder.

PMID- 28759549
TI  - The Reply.

PMID- 28759550
TI  - Surviving the NCLEX Dip.
AB  - Schools of nursing are charged with preparing graduates to meet minimal practice
      standards upon workforce entry. To that end, students must pass the National
      Council of State Boards of Nursing Licensure Examination (NCLEX-RN(r)) upon
      graduation. Increased rigor and higher recent passing standards for the exam can
      contribute to declining scores, which negatively impact graduates and the nursing
      program. The purpose of this article is to describe a successful 10-step action
      plan implemented to remediate a brief dip in NCLEX-RN pass rates at one
      university. The plan contributed to a 10 percent increase in NCLEX scores within
      one year.

PMID- 28759551
TI  - Pathways to BSN Education: Teamwork in Ohio.
AB  - AIM: The Ohio Action Coalition was formed to address the key recommendations of
      the Institute of Medicine's Future of Nursing report. BACKGROUND: The Future of
      Nursing Campaign for Action is a national initiative to guide implementation of
      the recommendations in the Future of Nursing report. METHOD: Through statewide
      meetings, leaders from nursing education and practice adopted a statewide
      competency model. Regional teams provided detailed regional gap analyses using
      the Ohio Nurse Competency Model and address the Institute of Medicine's
      foundational pillar that nurses should achieve higher levels of education.
      RESULTS: Communication among baccalaureate and community colleges and nursing
      practice has increased statewide as a result of this collaborative project. The
      teams are committed to exploring ways to standardize and develop adaptable
      seamless academic progression models for implementation across communities.
      CONCLUSION: Ultimately, the goal is to positively impact the academic preparation
      of the Ohio nursing workforce.

PMID- 28759552
TI  - Flipping an Undergraduate Gerontological Nursing Course: Student Perceptions.
AB  - A flipped classroom instructional method was implemented in a gerontological
      nursing course. Students were surveyed to evaluate their perceptions of the
      flipped classroom module as well as their satisfaction with it. Open-ended
      questions were used to explore the students' best and least favorite aspects of
      the format. Results indicated that, overall, students were satisfied with and
      received benefits from the new format; some students experienced frustration in
      the nonpassive classroom setting. Additional research is needed to determine how
      to meet the needs of these students and which undergraduate nursing courses are
      suited for the flipped classroom format.

PMID- 28759553
TI  - Examining Mosquito Surveillance and Control Capacity in the Top 10 Areas at Risk
      for Zika Virus Exposure in the United States.

PMID- 28759554
TI  - ASTHO at 75: Celebrating the Past and Preparing for the Future.

PMID- 28759555
TI  - Celebrating 75 Years of ASTHO: Milestones in Public Health Leadership.

PMID- 28759556
TI  - 2017 ASTHO President's Challenge: Public Health Approaches to Preventing
      Substance Misuse and Addiction.

PMID- 28759557
TI  - High Turnover Among State Health Officials/Public Health Directors: Implications
      for the Public's Health.
AB  - CONTEXT: State health officials (SHOs) serve a critical role as the leaders of
      state public health systems. Despite their many responsibilities, there is no
      formal process for preparation to become an SHO, and few requirements influence
      the selection of an SHO. Furthermore, to date, no studies have examined SHO
      tenure or their experiences. OBJECTIVE: This study examines SHO tenure over time
      and the relationship between SHO tenure and organizational and state attributes.
      DESIGN: This longitudinal study employed primary data on SHOs and secondary data
      from the Association of State and Territorial Health Officials on organizational
      attributes of state public health agencies. SETTING: This study examines SHOs
      within the United States. PARTICIPANTS: SHOs who served in years 1980-2017. MAIN
      OUTCOME MEASURES: Annual average SHO tenure; average SHO tenure by state.
      RESULTS: In the 38 years of this study, 508 individuals served as SHOs in the 50
      states and the District of Columbia. The average tenure over this period was 4.1
      years, with a median tenure of 2.9 years. During the study period, almost 20% of
      SHOs served terms of 1 year or less. A total of 32 SHOs (32/508 or 6.3%) served
      for 10 years or longer. Excluding SHOs who served 10 years or longer (n = 32 SHOs
      who had a collective 478 years of tenure) reduces the average term in office to
      3.5 years. The average number of new SHOs per year is 12.3. SHOs appointed by a
      board of health averaged more than 8 years in office compared with averages just
      under 4 years for those appointed by governors or secretaries of state agencies.
      CONCLUSIONS: There are notable differences in SHO tenure across states. Future
      research is needed to further examine SHO tenure, effectiveness, job
      satisfaction, transitions, and the relationship between SHOs and state health. It
      may be valuable to expand on opportunities for new SHOs to learn from peers who
      have moderate to long tenures as well as SHO alumni. Given that average SHO
      tenure is approximately 4 years and that an SHO could be thrust into the national
      spotlight at a moment's notice, governors may want to consider experience over
      partisanship as they appoint new SHOs.

PMID- 28759558
TI  - Beyond the Status Quo: 5 Strategic Moves to Position State and Territorial Public
      Health Agencies for an Uncertain Future.

PMID- 28759559
TI  - Ethambutol optic neuropathy.
AB  - PURPOSE OF REVIEW: We provide a summary of the epidemiology, clinical findings,
      management and outcomes of ethambutol-induced optic neuropathy (EON). Ethambutol
      induced optic neuropathy is a well-known, potentially irreversible, blinding but
      largely preventable disease. Clinicians should be aware of the importance of
      patient and physician education as well as timely and appropriate screening.
      RECENT FINDINGS: Two of the largest epidemiologic studies investigating EON to
      date showed the prevalence of EON in all patients taking ethambutol to be between
      0.7 and 1.29%, a value consistent with previous reports of patients taking the
      doses recommended by the World Health Organization (WHO). Several studies
      evaluated the utility of optical coherence tomography (OCT) in screening for EON.
      These showed decreased retinal nerve fiber layer (RNFL) thickness in patients
      with clinically significant EON, but mixed results in their ability to detect
      such changes in patients taking ethambutol without visual symptoms. SUMMARY:
      Ethambutol-induced optic neuropathy is a well-known and devastating complication
      of ethambutol therapy. It may occur in approximately 1% of patients taking
      ethambutol at the WHO recommended doses, though the risk increases substantially
      with increased dose. All patients on ethambutol should receive regular screening
      by an ophthalmologist including formal visual field testing. Visual evoked
      potentials and OCT may be helpful for EON screening, but more research is needed
      to clarify their clinical usefulness. Patients who develop signs or symptoms of
      EON should be referred to the ethambutol-prescribing physician immediately for
      discontinuation or a reduction in ethambutol dosing.

PMID- 28759560
TI  - Ophthalmic and neuro-ophthalmic manifestations of sarcoidosis.
AB  - PURPOSE OF REVIEW: Sarcoidosis is a multisystemic inflammatory disease that
      commonly affects the eye and less often the neuro-ophthalmic pathways. The
      manifestations can be quite variable but can have characteristic signs and
      clinical features. This review provides a comprehensive overview of the various
      ocular and neuro-ophthalmic manifestations of sarcoidosis, emerging diagnostic
      measures and approach to treatment. Particular focus is given to recent advances
      in diagnostic approach and available treatment options. RECENT FINDINGS:
      Laboratory investigations, chest and nuclear medicine imaging remain important
      techniques for helping to diagnose sarcoidosis. Recent evidence suggests a role
      for aqueous humor analysis in the diagnosis of ocular sarcoidosis. Characteristic
      neuroimaging may help differentiate neurosarcoidosis from other causes. The role
      of blind conjunctival biopsy for suspected neurosarcoidosis is discussed. The
      emerging role and use of biologics is delineated for the treatment of both ocular
      and neuro-ophthalmic sarcoidosis. SUMMARY: Sarcoidosis can affect any part of the
      visual system: the most common ocular manifestation is uveitis and the most
      common neuro-ophthalmic manifestation is optic neuropathy. Although diagnosis
      remains challenging, recent advancements in diagnosis are promising. Emerging
      biologics with particular efficacy for ocular and neuro-ophthalmic disease
      provide expanding treatment options for sight-threatening disease.

PMID- 28759561
TI  - Regenerating Family Member 4 (Reg4) Enhances 5-Fluorouracil Resistance of Gastric
      Cancer Through Activating MAPK/Erk/Bim Signaling Pathway.
AB  - BACKGROUND Reg4, a member of the Reg multigene family, is highly upregulated in
      many gastrointestinal cancers including gastric cancer (GC). The enhanced
      expression of Reg4 is associated with the resistance of GC to 5-fluorouracil (5
      FU), while the underlying mechanism is not clear. The aim of the present study
      was to explore the resistant mechanism underlying 5-FU resistance. MATERIAL AND
      METHODS Reg4 expression was assessed by Western blot analysis for SGC-7901, BGC
      823, AGS, MKN28, and MKN45. Synthetic short single strand RNA oligonucleotides
      and Flag-Reg4 plasmid were used to investigate the biological function of Reg4 in
      vitro. The cell viability assay was performed by MTT. Flow cytometry was carried
      out to measure the apoptosis caused by 5-FU. Reverse-transcriptase quantitative
      polymerase chain reaction (RT-qPCR) was used to examine the expression of 5-FU
      metabolism related enzymes. The effect of Reg4 on intracellular signaling was
      evaluated by Western blot. RESULTS Western blot analysis of 5 GC cells showed
      that Reg4 was low or null in SGC-7901 and BGC-823, while high in AGS, MKN28, and
      MKN45. Over-expression of flag-Reg4 in SGC-7901 led to an increase in cell
      viability and lower apoptosis with 5-FU treatment. In contrast, siRNA knockdown
      of Reg4 enhanced 5-FU induced apoptosis. However, over-expression or knockdown of
      Reg4 had no significant influence on the expression of 5-FU metabolic enzymes.
      Further investigation revealed that Reg4 could activate Erk1/2-Bim-caspase3
      cascade. CONCLUSIONS Reg4 inhibited apoptosis through regulating MAPK/Erk/Bim
      signaling pathway and thereby enhanced the resistance of GC to 5-FU.

PMID- 28759562
TI  - Learning and executing goal-directed choices by internally generated sequences in
      spiking neural circuits.
AB  - Recent neural ensemble recordings have established a link between goal-directed
      spatial decision making and internally generated neural sequences in the
      hippocampus of rats. To elucidate the synaptic mechanisms of these sequences
      underlying spatial decision making processes, we develop and investigate a
      spiking neural circuit model endowed with a combination of two synaptic
      plasticity mechanisms including spike-timing dependent plasticity (STDP) and
      synaptic scaling. In this model, the interplay of the combined synaptic
      plasticity mechanisms and network dynamics gives rise to neural sequences which
      propagate ahead of the animals' decision point to reach goal locations. The
      dynamical properties of these forward-sweeping sequences and the rates of correct
      binary choices executed by these sequences are quantitatively consistent with
      experimental observations; this consistency, however, is lost in our model when
      only one of STDP or synaptic scaling is included. We further demonstrate that
      such sequence-based decision making in our network model can adaptively respond
      to time-varying and probabilistic associations of cues and goal locations, and
      that our model performs as well as an optimal Kalman filter model. Our results
      thus suggest that the combination of plasticity phenomena on different timescales
      provides a candidate mechanism for forming internally generated neural sequences
      and for implementing adaptive spatial decision making.

PMID- 28759563
TI  - The costs of saving nature: Does it make "cents"?
AB  - Clearing wild forests to grow food, fibre, and fuel products can deliver large
      financial gains. However, the benefits that people obtain from forests-known as
      ecosystem services-are rarely considered in economic calculations, partly because
      there are few markets onto which they can be traded. In some regions, the
      benefits delivered by nature might be more economically valuable. A new study
      maps where it is profitable to replace tropical forests with cropland and how
      this might change under future agricultural production and carbon prices. The
      findings address a major applied challenge by helping to identify sites where
      forest conservation can be economically viable.

PMID- 28759564
TI  - De novo assembly and annotation of the retinal transcriptome for the Nile grass
      rat (Arvicanthis ansorgei).
AB  - Cone photoreceptors are required for color vision and high acuity vision, and
      they die in a variety of retinal degenerations, leading to irreversible vision
      loss and reduced quality of life. To date, there are no approved therapies that
      promote the health and survival of cones. The development of novel treatments
      targeting cones has been challenging and impeded, in part, by the limitations
      inherent in using common rodent model organisms, which are nocturnal and rod
      dominant, to study cone biology. The African Nile grass rat (Arvicanthis
      ansorgei), a diurnal animal whose photoreceptor population is more than 30%
      cones, offers significant potential as a model organism for the study of cone
      development, biology, and degeneration. However, a significant limitation in
      using the A. ansorgei retina for molecular studies is that A. ansorgei does not
      have a sequenced genome or transcriptome. Here we present the first de novo
      assembled and functionally annotated transcriptome for A. ansorgei. We performed
      RNA sequencing for A. ansorgei whole retina to a depth of 321 million pairs of
      reads and assembled 400,584 Trinity transcripts. Transcriptome-wide analyses and
      annotations suggest that our data set confers nearly full length coverage for the
      majority of retinal transcripts. Our high quality annotated transcriptome is
      publicly available, and we hope it will facilitate wider usage of A. ansorgei as
      a model organism for molecular studies of cone biology and retinal degeneration.

PMID- 28759565
TI  - Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by
      dendritic cells to enhance regulatory T cell conversion.
AB  - Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation
      stages that can convert naive T cells into Foxp3+ induced regulatory T cells
      (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with
      cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules
      using either high or low doses of CT (CThi, CTlo) or with cAMP, a known mediator
      CT signals. However, all three conditions also induced mRNA of both isoforms of
      the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2alpha and CTLA
      2beta). Only DCs matured under CThi conditions secreted IL-1beta, IL-6 and IL-23
      leading to the instruction of Th17 cell polarization. In contrast, CTlo- or cAMP
      DCs resembled semi-mature DCs and enhanced TGF-beta-dependent Foxp3+ iTreg
      conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and
      reversely, addition of recombinant CTLA-2alpha increased iTreg conversion in
      vitro. Injection of CTlo- or cAMP-DCs exerted MOG peptide-specific protective
      effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3+
      Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by
      DCs as a novel tolerogenic mediator of TGF-beta-mediated iTreg induction in vitro
      and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may
      point to a novel immune evasion mechanism of Vibrio cholerae.

PMID- 28759566
TI  - Influence of pyrethroid-treated bed net on host seeking behavior of Anopheles
      gambiae s.s. carrying the kdr allele.
AB  - The use of long lasting insecticide nets (LLINs) treated with pyrethroid is known
      for its major contribution in malaria control. However, LLINs are suspected to
      induce behavioral changes in malaria vectors, which may in turn drastically
      affect their efficacy against Plasmodium sp. transmission. In sub Saharan Africa,
      where malaria imposes the heaviest burden, the main malaria vectors are widely
      resistant to pyrethroids, the insecticide family used on LLINs, which also
      threatens LLIN efficiency. There is therefore a crucial need for deciphering how
      insecticide-impregnated materials might affect the host-seeking behavior of
      malaria vectors in regards to insecticide resistance. In this study, we explored
      the impact of permethrin-impregnated net on the host attractiveness for Anopheles
      gambiae mosquitoes, either susceptible to insecticides, or carrying the
      insecticide resistance conferring allele kdr. Groups of female mosquitoes were
      released in a dual-choice olfactometer and their movements towards an attractive
      odor source (a rabbit) protected by insecticide-treated (ITN) or untreated nets
      (UTN) were monitored. Kdr homozygous mosquitoes, resistant to insecticides, were
      more attracted by a host behind an ITN than an UTN, while the presence of
      insecticide on the net did not affect the choice of susceptible mosquitoes. These
      results suggest that permethrin-impregnated net is detectable by malaria vectors
      and that the kdr mutation impacts their response to a LLIN protected host. We
      discuss the implication of these results for malaria vector control.

PMID- 28759567
TI  - Functional neural circuits that underlie developmental stuttering.
AB  - The aim of this study was to identify differences in functional and effective
      brain connectivity between persons who stutter (PWS) and typically developing
      (TD) fluent speakers, and to assess whether those differences can serve as
      biomarkers to distinguish PWS from TD controls. We acquired resting-state
      functional magnetic resonance imaging data in 44 PWS and 50 TD controls. We then
      used Independent Component Analysis (ICA) together with Hierarchical Partner
      Matching (HPM) to identify networks of robust, functionally connected brain
      regions that were highly reproducible across participants, and we assessed
      whether connectivity differed significantly across diagnostic groups. We then
      used Granger Causality (GC) to study the causal interactions (effective
      connectivity) between the regions that ICA and HPM identified. Finally, we used a
      kernel support vector machine to assess how well these measures of functional
      connectivity and granger causality discriminate PWS from TD controls. Functional
      connectivity was stronger in PWS compared with TD controls in the supplementary
      motor area (SMA) and primary motor cortices, but weaker in inferior frontal
      cortex (IFG, Broca's area), caudate, putamen, and thalamus. Additionally, causal
      influences were significantly weaker in PWS from the IFG to SMA, and from the
      basal ganglia to IFG through the thalamus, compared to TD controls. ICA and GC
      indices together yielded an accuracy of 92.7% in classifying PWS from TD
      controls. Our findings suggest the presence of dysfunctional circuits that
      support speech planning and timing cues for the initiation and execution of motor
      sequences in PWS. Our high accuracy of classification further suggests that these
      aberrant brain features may serve as robust biomarkers for PWS.

PMID- 28759568
TI  - Cannabinoid receptor 2-63 RR variant is independently associated with severe
      necroinflammation in HIV/HCV coinfected patients.
AB  - OBJECTIVE: This is the first study to analyze the impact of the rs35761398
      variant of the CNR2 gene leading to the substitution of GLN (Q) of codon 63 of
      the cannabinoid receptor 2 (CB2) with ARG (R) on the clinical presentation of
      chronic hepatitis in HIV/HCV coinfected patients. METHODS: Enrolled in this study
      were 166 consecutive HIV/HCV coinfected patients, naive for HCV treatment. A
      pathologist unaware of the patients' condition graded liver fibrosis,
      necroinflammation (Ishak) and steatosis. All patients were screened for the CB2
      rs35761398 polymorphism. RESULTS: Of the 166 HIV/HCV coinfected patients, 72.9%
      were males, 42.5% were infected with HCV-genotype-3 and 60.2% had been
      intravenous drug users. The median age was 40.6 years and the immunological
      condition good (median CD4+ cells/mm3 = 507, IQR: 398.0-669.5). Thirty-five
      (21.1%) patients were naive for ART and 131(78.9%) were on ART. The CB2-RR
      variant was detected in 45.8% of patients, QR in 38.6% and QQ in 15.7%. Patients
      with CB2-RR showed a necroinflammation score (HAI) >=9 more frequently than those
      with CB2-QQ or CB2-QR (32.9% vs. 11.5% and 14.1%, respectively, p<=0.001). In the
      multivariate analysis, the CB2-RR variant (p = 0.03) and liver fibrosis were both
      identified as independent predictors of the entity of liver necroinflammation (p
      = 0.0001). CONCLUSION: This study shows interesting interplay between the CB2-RR
      variant and liver necroinflammation in chronic hepatitis patients with HIV/HCV
      coinfection, an observation of clinical value that coincides with the interest in
      the use of the CB2 agonists and antagonists in clinical practice emerging from
      the literature.

PMID- 28759569
TI  - Proposed equations and reference values for calculating bone health in children
      and adolescent based on age and sex.
AB  - BACKGROUND: The Dual Energy X-Ray Absorptiometry (DXA) is the gold standard for
      measuring BMD and bone mineral content (BMC). In general, DXA is ideal for
      pediatric use. However, the development of specific standards for particular
      geographic regions limits its use and application for certain socio-cultural
      contexts. Additionally, the anthropometry may be a low cost and easy to use
      alternative method in epidemiological contexts. The goal of our study was to
      develop regression equations for predicting bone health of children and
      adolescents based on anthropometric indicators to propose reference values based
      on age and sex. METHODS: 3020 students (1567 males and 1453 females) ranging in
      ages 4.0 to 18.9 were studied from the Maule Region (Chile). Anthropometric
      variables evaluated included: weight, standing height, sitting height, forearm
      length, and femur diameter. A total body scan (without the head) was conducted by
      means of the Dual Energy X-Ray Absorptiometry. Bone mineral density (BMD) and the
      bone mineral content (BMC) were also determined. Calcium consumption was
      controlled for by recording the intake of the three last days prior to the
      evaluation. Body Mass Index (BMI) was calculated, and somatic maturation was
      determined by using the years of peak growth rate (APHV). RESULTS: Four
      regression models were generated to calculate bone health: for males BMD = (R2 =
      0.79) and BMC = (R2 = 0.84) and for the females BMD = (R2 = 0.76) and BMC = (R2 =
      0.83). Percentiles were developed by using the LMS method (p3, p5, p15, p25, p50,
      p75, p85, p95 and p97). CONCLUSIONS: Regression equations and reference curves
      were developed to assess the bone health of Chilean children and adolescents.
      These instruments help identify children with potential underlying problems in
      bone mineralization during the growth stage and biological maturation.

PMID- 28759571
TI  - Chicken hepatic response to chronic heat stress using integrated transcriptome
      and metabolome analysis.
AB  - The liver plays a central role in metabolism and is important in maintaining
      homeostasis throughout the body. This study integrated transcriptomic and
      metabolomic data to understand how the liver responds under chronic heat stress.
      Chickens from a rapidly growing broiler line were heat stressed for 8 hours per
      day for one week and liver samples were collected at 28 days post hatch.
      Transcriptome analysis reveals changes in genes responsible for cell cycle
      regulation, DNA replication, and DNA repair along with immune function.
      Integrating the metabolome and transcriptome data highlighted multiple pathways
      affected by heat stress including glucose, amino acid, and lipid metabolism along
      with glutathione production and beta-oxidation.

PMID- 28759570
TI  - cAMP-dependent activation of protein kinase A attenuates respiratory syncytial
      virus-induced human airway epithelial barrier disruption.
AB  - Airway epithelium forms a barrier to the outside world and has a crucial role in
      susceptibility to viral infections. Cyclic adenosine monophosphate (cAMP) is an
      important second messenger acting via two intracellular signaling molecules:
      protein kinase A (PKA) and the guanidine nucleotide exchange factor, Epac. We
      sought to investigate effects of increased cAMP level on the disruption of model
      airway epithelial barrier caused by RSV infection and the molecular mechanisms
      underlying cAMP actions. Human bronchial epithelial cells were infected with RSV
      A2 and treated with either cAMP releasing agent, forskolin, or cAMP analogs.
      Structure and functions of the Apical Junctional Complex (AJC) were evaluated by
      measuring transepithelial electrical resistance and permeability to FITC-dextran,
      and determining localization of AJC proteins by confocal microscopy. Increased
      intracellular cAMP level significantly attenuated RSV-induced disassembly of AJC.
      These barrier-protective effects of cAMP were due to the activation of PKA
      signaling and did not involve Epac activity. Increased cAMP level reduced RSV
      induced reorganization of the actin cytoskeleton, including apical accumulation
      of an essential actin-binding protein, cortactin, and inhibited expression of the
      RSV F protein. These barrier-protective and antiviral-function of cAMP signaling
      were evident even when cAMP level was increased after the onset of RSV infection.
      Taken together, our study demonstrates that cAMP/PKA signaling attenuated RSV
      induced disruption of structure and functions of the model airway epithelial
      barrier by mechanisms involving the stabilization of epithelial junctions and
      inhibition of viral biogenesis. Improving our understanding of the mechanisms
      involved in RSV-induced epithelial dysfunction and viral pathogenesis will help
      to develop novel anti-viral therapeutic approaches.

PMID- 28759572
TI  - The naked truth about HIV and risk taking in Swedish prisons: A qualitative
      study.
AB  - BACKGROUND: This qualitative study explores former prison inmates' perceptions
      and attitudes towards HIV risk inside Swedish prisons. METHOD: In 2014, eight
      semi-structured interviews were conducted with former male prisoners to gain a
      deeper understanding of situations perceived to be associated with risk of HIV
      transmission. The material gathered from the interviews was analyzed by manifest
      and latent qualitative content analysis. RESULTS: The findings revealed that
      risky behavioral practices, such as sharing needles, unprotected sexual activity,
      and lack of openness about HIV status represented potential health threats with
      regard to the risk of HIV transmission. CONCLUSIONS: Evidence from the study
      indicates that educational interventions regarding HIV and the transmission
      routes are required for HIV prevention in Swedish prisons.

PMID- 28759573
TI  - Alternation of plasma fatty acids composition and desaturase activities in
      children with liver steatosis.
AB  - OBJECTIVE: The aim of this study was to investigate changes in plasma fatty acids
      proportions and estimated desaturase activities for variable grading of liver
      steatosis in children. METHODS: In total, 111 schoolchildren (aged 8-18 years)
      were included in the analysis from March 2015 to August 2016. Anthropometric
      evaluation, liver ultrasound examination and scoring for nonalcoholic fatty liver
      disease (NAFLD score = 0-6), and biochemical and plasma fatty acids analysis were
      performed. We compared the composition ratio of fatty acids between children with
      high-grade liver steatosis (NAFLD score = 4-6), low-grade liver steatosis (NAFLD
      score = 1-3), and healthy controls (NAFLD score = 0). In addition, correlation
      coefficients (r) between NAFLD score, metabolic variables, and estimated activity
      of desaturase indices (stearoyl-coenzyme A desaturase-1 (SCD1), delta-5 and delta
      6 desaturase) were calculated. RESULTS: Compared with healthy controls, children
      with liver steatosis showed a higher proportion of monounsaturated fatty acids
      (21.16 +/- 2.81% vs. 19.68 +/- 2.71%, p = 0.024). In addition, children with high
      grade liver steatosis exhibited higher proportions of palmitic acid (C16:0),
      palmitoleic acid (C16:1n-7), dihomo-gamma-linolenic acid (C20:3n-6), adrenic acid
      (C22:4n-6), and docosapentaenoic acid (C22:5n-6); and lower proportions of
      eicosapentaenoic acid (C20:5n-3) (P< 0.05). In all subjects, the NAFLD score was
      positively correlated with body mass index (BMI) (kg/m2) (r = 0.696), homeostasis
      model of assessment ratio-index (HOMA-IR) (r = 0.510), SCD1(16) (r = 0.273), and
      the delta-6 index (r = 0.494); and inversely associated with the delta-5 index (r
      = -0.443). CONCLUSION: Our current data suggested that children with liver
      steatosis was highly associated with obesity, and insulin resistance. In
      addition, increased endogenous lipogenesis through altered desaturase activity
      may contribute to the progression of liver steatosis in children.

PMID- 28759575
TI  - Barriers to sexual and reproductive healthcare services as experienced by female
      sex workers and service providers in Dhaka city, Bangladesh.
AB  - OBJECTIVES: This study aimed to identify the barriers female sex workers (FSWs)
      in Bangladesh face with regard to accessing sexual and reproductive health (SRH)
      care, and assess the satisfaction with the healthcare received. METHODS: Data
      were collected from coverage areas of four community-based drop-in-centers (DICs)
      in Dhaka where sexually transmitted infection (STI) and human immunovirus (HIV)
      prevention interventions have been implemented for FSWs. A total of 731 FSWs aged
      15-49 years were surveyed. In addition, in-depth interviews (IDIs) were conducted
      with 14 FSWs and 9 service providers. Respondent satisfaction was measured based
      on recorded scores on dignity, privacy, autonomy, confidentiality, prompt
      attention, access to social support networks during care, basic amenities, and
      choice of institution/care provider. RESULTS: Of 731 FSWs, 353 (51%) reported
      facing barriers when seeking sexual and reproductive healthcare. Financial
      problems (72%), shame about receiving care (52.3%), unwillingness of service
      providers to provide care (39.9%), unfriendly behavior of the provider (24.4%),
      and distance to care (16.9%) were mentioned as barriers. Only one-third of the
      respondents reported an overall satisfaction score of more than fifty percent (a
      score of between 9 and16) with formal healthcare. Inadequacy or lack of SRH
      services and referral problems (e.g., financial charge at referral centers,
      unsustainable referral provision, or unknown location of referral) were reported
      by the qualitative FSWs as the major barriers to accessing and utilizing SRH
      care. CONCLUSIONS: These findings are useful for program implementers and policy
      makers to take the necessary steps to reduce or remove the barriers in the health
      system that are preventing FSWs from accessing SRH care, and ultimately meet the
      unmet healthcare needs of FSWs.

PMID- 28759574
TI  - Differential regulation of germ line apoptosis and germ cell differentiation by
      CPEB family members in C. elegans.
AB  - Cytoplasmic polyadenylation element binding (CPEB) proteins are evolutionary
      conserved RNA-binding proteins that control mRNA polyadenylation and translation.
      Orthologs in humans and other vertebrates are mainly involved in oogenesis. This
      is also the case for the C. elegans CPEB family member CPB-3, whereas two further
      CPEB proteins (CPB-1 and FOG-1) are involved in spermatogenesis. Here we describe
      the characterisation of a new missense allele of cpb-3 and show that loss of cpb
      3 function leads to an increase in physiological germ cell death. To better
      understand the interaction and effect of C. elegans CPEB proteins on processes
      such as physiological apoptosis, germ cell differentiation, and regulation of
      gene expression, we characterised changes in the transcriptome and proteome of C.
      elegans CPEB mutants. Our results show that, despite their sequence similarities
      CPEB family members tend to have distinct overall effects on gene expression
      (both at the transcript and protein levels). This observation is consistent with
      the distinct phenotypes observed in the various CPEB family mutants.

PMID- 28759576
TI  - Predicting spatial spread of rabies in skunk populations using surveillance data
      reported by the public.
AB  - BACKGROUND: Prevention and control of wildlife disease invasions relies on the
      ability to predict spatio-temporal dynamics and understand the role of factors
      driving spread rates, such as seasonality and transmission distance. Passive
      disease surveillance (i.e., case reports by public) is a common method of
      monitoring emergence of wildlife diseases, but can be challenging to interpret
      due to spatial biases and limitations in data quantity and quality.
      METHODOLOGY/PRINCIPAL FINDINGS: We obtained passive rabies surveillance data from
      dead striped skunks (Mephitis mephitis) in an epizootic in northern Colorado,
      USA. We developed a dynamic patch-occupancy model which predicts spatio-temporal
      spreading while accounting for heterogeneous sampling. We estimated the distance
      travelled per transmission event, direction of invasion, rate of spatial spread,
      and effects of infection density and season. We also estimated mean transmission
      distance and rates of spatial spread using a phylogeographic approach on a
      subsample of viral sequences from the same epizootic. Both the occupancy and
      phylogeographic approaches predicted similar rates of spatio-temporal spread.
      Estimated mean transmission distances were 2.3 km (95% Highest Posterior Density
      (HPD95): 0.02, 11.9; phylogeographic) and 3.9 km (95% credible intervals (CI95):
      1.4, 11.3; occupancy). Estimated rates of spatial spread in km/year were: 29.8
      (HPD95: 20.8, 39.8; phylogeographic, branch velocity, homogenous model), 22.6
      (HPD95: 15.3, 29.7; phylogeographic, diffusion rate, homogenous model) and 21.1
      (CI95: 16.7, 25.5; occupancy). Initial colonization probability was twice as high
      in spring relative to fall. CONCLUSIONS/SIGNIFICANCE: Skunk-to-skunk transmission
      was primarily local (< 4 km) suggesting that if interventions were needed, they
      could be applied at the wave front. Slower viral invasions of skunk rabies in
      western USA compared to a similar epizootic in raccoons in the eastern USA
      implies host species or landscape factors underlie the dynamics of rabies
      invasions. Our framework provides a straightforward method for estimating rates
      of spatial spread of wildlife diseases.

PMID- 28759577
TI  - Modular function of long noncoding RNA, COLDAIR, in the vernalization response.
AB  - The long noncoding RNA COLDAIR is necessary for the repression of a floral
      repressor FLOWERING LOCUS C (FLC) during vernalization in Arabidopsis thaliana.
      The repression of FLC is mediated by increased enrichment of Polycomb Repressive
      Complex 2 (PRC2) and subsequent trimethylation of Histone H3 Lysine 27 (H3K27me3)
      at FLC chromatin. In this study we found that the association of COLDAIR with
      chromatin occurs only at the FLC locus and that the central region of the COLDAIR
      transcript is critical for this interaction. A modular motif in COLDAIR is
      responsible for the association with PRC2 in vitro, and the mutations within the
      motif that reduced the association of COLDAIR with PRC2 resulted in vernalization
      insensitivity. The vernalization insensitivity caused by mutant COLDAIR was
      rescued by the ectopic expression of the wild-type COLDAIR. Our study reveals the
      molecular framework in which COLDAIR lncRNA mediates the PRC2-mediated repression
      of FLC during vernalization.

PMID- 28759578
TI  - Heterologous expression of the antimyotoxic protein DM64 in Pichia pastoris.
AB  - Snakebite envenomation is a neglected condition that constitutes a public health
      problem in tropical and subtropical countries, including Brazil. Interestingly,
      some animals are resistant to snake envenomation due to the presence of
      inhibitory glycoproteins in their serum that target toxic venom components. DM64
      is an acidic glycoprotein isolated from Didelphis aurita (opossum) serum that has
      been characterized as an inhibitor of the myotoxicity induced by bothropic toxins
      bearing phospholipase A2 (PLA2) structures. This antitoxic protein can serve as
      an excellent starting template for the design of novel therapeutics against
      snakebite envenomation, particularly venom-induced local tissue damage.
      Therefore, the aim of this work was to produce a recombinant DM64 (rDM64) in the
      methylotrophic yeast Pichia pastoris and to compare its biological properties
      with those of native DM64. Yeast fermentation in the presence of Pefabloc, a
      serine protease inhibitor, stimulated cell growth (~1.5-fold), increased the
      rDM64 production yield approximately 10-fold and significantly reduced the
      susceptibility of rDM64 to proteolytic degradation. P. pastoris fermentation
      products were identified by mass spectrometry and Western blotting. The
      heterologous protein was efficiently purified from the culture medium by affinity
      chromatography (with immobilized PLA2 myotoxin) and/or an ion exchange column.
      Although both native and recombinant DM64 exhibit different glycosylation
      patterns, they show very similar electrophoretic mobilities after PNGase F
      treatment. rDM64 formed a noncovalent complex with myotoxin II (Lys49-PLA2) from
      Bothrops asper and displayed biological activity that was similar to that of
      native DM64, inhibiting the cytotoxicity of myotoxin II by 92% at a 1:1 molar
      ratio.

PMID- 28759580
TI  - Knowledge, attitudes and practices towards yaws and yaws-like skin disease in
      Ghana.
AB  - INTRODUCTION: Yaws is endemic in Ghana. The World Health Organization (WHO) has
      launched a new global eradication campaign based on total community mass
      treatment with azithromycin. Achieving high coverage of mass treatment will be
      fundamental to the success of this new strategy; coverage is dependent, in part,
      on appropriate community mobilisation. An understanding of community knowledge,
      attitudes and practices related to yaws in Ghana and other endemic countries will
      be vital in designing effective community engagement strategies. METHODS: A
      verbally administered questionnaire was administered to residents in 3 districts
      in the Eastern region of Ghana where a randomised trial on the treatment of yaws
      was being conducted. The questionnaire combined both quantitative and qualitative
      questions covering perceptions of the cause and mechanisms of transmission of
      yaws-like lesions, the providers from which individuals would seek healthcare for
      yaws-like lesions, and what factors were important in reaching decisions on where
      to seek care. Chi-square tests and logistic regression were used to assess
      relationships between reported knowledge, attitudes and practices, and
      demographic variables. Thematic analysis of qualitative data was used to identify
      common themes. RESULTS: A total of 1,162 individuals participated. The majority
      of individuals (n = 895, 77%) reported that "germs" were the cause of yaws
      lesions. Overall 13% (n = 161) of respondents believed that the disease was
      caused by supernatural forces. Participants frequently mentioned lack of personal
      hygiene, irregular and inefficient bathing, and washing with dirty water as
      fundamental to both the cause and the prevention of yaws. A majority of
      individuals reported that they would want to take an antibiotic to prevent the
      development of yaws if they were asymptomatic (n = 689, 61.2%), but a substantial
      minority reported they would not want to do so. A majority of individuals (n =
      839, 72.7%) reported that if they had a yaws-like skin lesion they would seek
      care from a doctor or nurse. Both direct and indirect costs of treatment were
      reported as key factors affecting where participants reported they would seek
      care. DISCUSSION: This is the first study that has explored community knowledge,
      attitudes and practices in relation to yaws in any endemic population. The belief
      that 'germs' are in some way related to disease through a variety of transmission
      routes including both contact and dirty water are similar to those reported for
      other skin diseases in Ghana. The prominent role of private healthcare providers
      is an important finding of this study and suggests engagement with this sector
      will be important in yaws eradication efforts. Strategies to address the
      substantial minority of individuals who reported they would not take treatment
      for yaws if they were currently asymptomatic will be needed to ensure the success
      of yaws eradication efforts. The data collected will be of value to the Ghana
      Health Service and also to WHO and other partners, who are currently developing
      community mobilisation tools to support yaws eradication efforts worldwide.

PMID- 28759579
TI  - Dynactin binding to tyrosinated microtubules promotes centrosome centration in C.
      elegans by enhancing dynein-mediated organelle transport.
AB  - The microtubule-based motor dynein generates pulling forces for centrosome
      centration and mitotic spindle positioning in animal cells. How the essential
      dynein activator dynactin regulates these functions of the motor is incompletely
      understood. Here, we dissect the role of dynactin's microtubule binding activity,
      located in the p150 CAP-Gly domain and an adjacent basic patch, in the C. elegans
      zygote. Analysis of p150 mutants engineered by genome editing suggests that
      microtubule tip tracking of dynein-dynactin is dispensable for targeting the
      motor to the cell cortex and for generating robust cortical pulling forces.
      Instead, mutations in p150's CAP-Gly domain inhibit cytoplasmic pulling forces
      responsible for centration of centrosomes and attached pronuclei. The centration
      defects are mimicked by mutations of alpha-tubulin's C-terminal tyrosine, and
      both p150 CAP-Gly and tubulin tyrosine mutants decrease the frequency of early
      endosome transport from the cell periphery towards centrosomes during centration.
      Our results suggest that p150 GAP-Gly domain binding to tyrosinated microtubules
      promotes initiation of dynein-mediated organelle transport in the dividing one
      cell embryo, and that this function of p150 is critical for generating
      cytoplasmic pulling forces for centrosome centration.

PMID- 28759581
TI  - The combination of circle topology and leaky integrator neurons remarkably
      improves the performance of echo state network on time series prediction.
AB  - Recently, echo state network (ESN) has attracted a great deal of attention due to
      its high accuracy and efficient learning performance. Compared with the
      traditional random structure and classical sigmoid units, simple circle topology
      and leaky integrator neurons have more advantages on reservoir computing of ESN.
      In this paper, we propose a new model of ESN with both circle reservoir structure
      and leaky integrator units. By comparing the prediction capability on Mackey
      Glass chaotic time series of four ESN models: classical ESN, circle ESN,
      traditional leaky integrator ESN, circle leaky integrator ESN, we find that our
      circle leaky integrator ESN shows significantly better performance than other
      ESNs with roughly 2 orders of magnitude reduction of the predictive error.
      Moreover, this model has stronger ability to approximate nonlinear dynamics and
      resist noise than conventional ESN and ESN with only simple circle structure or
      leaky integrator neurons. Our results show that the combination of circle
      topology and leaky integrator neurons can remarkably increase dynamical diversity
      and meanwhile decrease the correlation of reservoir states, which contribute to
      the significant improvement of computational performance of Echo state network on
      time series prediction.

PMID- 28759582
TI  - The association between A Body Shape Index and mortality: Results from an
      Australian cohort.
AB  - It is well recognised that obesity increases the risk of premature death. A Body
      Shape Index (ABSI) is a formula that uses waist circumference (WC), body mass
      index (BMI) and height to predict risk of premature mortality, where a high score
      (Quartile 4) indicates that a person's WC is more than expected given their
      height and weight. Our study examines the association between ABSI quartiles and
      all-cause-, cardiovascular- and cancer-related mortality, and primary cause of
      death. Self-reported demographic and biomedically measured health-related risk
      factor and weight data was from the baseline stage of the North West Adelaide
      Health Study (1999-2003, n = 4056), a longitudinal cohort of Australian adults.
      Death-related information was obtained from the National Death Index. Primary
      cause of death across ABSI quartiles was examined. The association between
      mortality and ABSI (quartile and continuous scores) was investigated using a Cox
      proportional hazards survival model and adjusting for socioeconomic, and self
      reported and biomedical risk factors. The proportion of all three types of
      mortality steadily increased from ABSI Quartile 1 through to Quartile 4. After
      adjusting for demographic and health-related risk factors, the risk of all-cause
      mortality was higher for people in ABSI Quartile 4 (HR 2.64, 95% CI 01.56-4.47),
      and ABSI Quartile 3 (HR 1.95, 95% CI 1.15-3.33), with a moderate association for
      the continuous ABSI score (HR 1.32, 95% CI 1.18-1.48). ABSI is therefore
      positively associated with mortality in Australian adults. Different combined
      measures of obesity such as the ABSI are useful in examining mortality risk.

PMID- 28759583
TI  - Control of chronic Strongyloides stercoralis infection in an endemic community
      may be possible by pharmacological means alone: Results of a three-year cohort
      study.
AB  - OBJECTIVES: To assess the effect of treatment with ivermectin on the prevalence
      of S. stercoralis infection in an Australian Aboriginal population over a three
      year period, and to assess the validity of using a lower ELISA cut-off in
      diagnosis. METHODS: A three-year cohort study of 259 adult Australian Aboriginals
      living in a remote community in northern Australia. S stercoralis infection was
      diagnosed using commercial ELISA testing, and employed a lower threshold for
      treatment than that recommended. Follow up was conducted at 6 months and 3 years
      following ivermectin treatment. FINDINGS: Treatment with ivermectin was highly
      effective and resulted in a sustained fall in the prevalence of infection in the
      study group (Initial prevalence 35.3%, 3 year prevalence 5.8%, McNemar's chi2 =
      56.5, p<0.001). Results of treatment suggested use of a lower ELISA threshold for
      treatment was valid in this setting. Follow up identified a small group of
      subjects with persistently positive ELISA serology despite repeated treatment.
      INTERPRETATION: Control of S. stercoralis infection in this cohort appears to be
      feasible using pharmacological treatment alone.

PMID- 28759584
TI  - A safety rule approach to surveillance and eradication of biological invasions.
AB  - Uncertainty about future spread of invasive organisms hinders planning of
      effective response measures. We present a two-stage scenario optimization model
      that accounts for uncertainty about the spread of an invader, and determines
      survey and eradication strategies that minimize the expected program cost subject
      to a safety rule for eradication success. The safety rule includes a risk
      standard for the desired probability of eradication in each invasion scenario.
      Because the risk standard may not be attainable in every scenario, the safety
      rule defines a minimum proportion of scenarios with successful eradication. We
      apply the model to the problem of allocating resources to survey and eradicate
      the Asian longhorned beetle (ALB, Anoplophora glabripennis) after its discovery
      in the Greater Toronto Area, Ontario, Canada. We use historical data on ALB
      spread to generate a set of plausible invasion scenarios that characterizes the
      uncertainty of the beetle's extent. We use these scenarios in the model to find
      survey and tree removal strategies that minimize the expected program cost while
      satisfying the safety rule. We also identify strategies that reduce the risk of
      very high program costs. Our results reveal two alternative strategies: (i)
      delimiting surveys and subsequent tree removal based on the surveys' outcomes, or
      (ii) preventive host tree removal without referring to delimiting surveys. The
      second strategy is more likely to meet the stated objectives when the capacity to
      detect an invader is low or the aspirations to eradicate it are high. Our results
      provide practical guidelines to identify the best management strategy given
      aspirational targets for eradication and spending.

PMID- 28759585
TI  - Today's medical self and the other: Challenges and evolving solutions for
      enhanced humanization and quality of care.
AB  - BACKGROUND: Recent scientific developments, along with growing awareness of
      cultural and social diversity, have led to a continuously growing range of
      available treatment options; however, such developments occasionally lead to an
      undesirable imbalance between science, technology and humanism in clinical
      practice. This study explores the understanding and practice of values and value
      clusters in real-life clinical settings, as well as their role in the
      humanization of medicine and its institutions. The research focuses on the values
      of clinical practice as a means of finding ways to enhance the pairing of
      Evidence-Based Medicine (EBM) with Values-based Medicine (VBM) in daily practice.
      METHODS AND FINDINGS: The views and representations of clinical practice in 15
      pre-CME and 15 post-CME interviews were obtained from a random sampling of active
      healthcare professionals. These views were then identified and qualitatively
      analyzed using a three-step hermeneutical approach. A clinical values space was
      identified in which ethical and epistemic values emerge, grow and develop within
      the biomedical, ethical, and socio-economic dimensions of everyday health care.
      Three main values-as well as the dynamic clusters and networks that they tend to
      form-were recognized: healthcare personnel-patient relationships, empathy, and
      respect. An examination of the interviews suggested that an adequate
      conceptualization of values leads to the formation of a wider axiological system.
      The role of clinician-as-consociate emerged as an ideal for achieving medical
      excellence. CONCLUSIONS: By showing the intricate clusters and networks into
      which values are interwoven, our analysis suggests methods for fine-tuning
      educational interventions so they can lead to demonstrable changes in attitudes
      and practices.

PMID- 28759586
TI  - Apology in cases of medical error disclosure: Thoughts based on a preliminary
      study.
AB  - BACKGROUND: Disclosing medical errors is considered necessary by patients,
      ethicists, and health care professionals. Literature insists on the framing of
      this disclosure and describes the apology as appropriate and necessary. However,
      this policy seems difficult to put into practice. Few works have explored the
      function and meaning of the apology. OBJECTIVE: The aim of this study was to
      explore the role ascribed to apology in communication between healthcare
      professionals and patients when disclosing a medical error, and to discuss these
      findings using a linguistic and philosophical perspective. METHODS: Qualitative
      exploratory study, based on face-to-face semi-structured interviews, with seven
      physicians in a neonatal unit in France. Discourse analysis. RESULTS: Four themes
      emerged. Difference between apology in everyday life and in the medical
      encounter; place of the apology in the process of disclosure together with
      explanations, regrets, empathy and ways to avoid repeating the error; effects of
      the apology were to allow the patient-physician relationship undermined by the
      error, to be maintained, responsibility to be accepted, the first steps towards
      forgiveness to be taken, and a less hierarchical doctor-patient relationship to
      be created; ways of expressing apology ("I am sorry") reflected regrets and
      empathy more than an explicit apology. CONCLUSION: This study highlights how the
      act of apology can be seen as a "language act" as described by philosophers
      Austin and Searle, and how it functions as a technique for making amends
      following a wrongdoing and as an action undertaken in order that neither party
      should lose face, thus echoing the sociologist Goffmann's interaction theory.
      This interpretation also accords with the views of Lazare, for whom the function
      of apology is a restoration of dignity after the humiliation of the error. This
      approach to the apology illustrates how meaning and impact of real-life language
      acts can be clarified by philosophical and sociological ideas.

PMID- 28759587
TI  - Older adults must hurry at pedestrian lights! A cross-sectional analysis of
      preferred and fast walking speed under single- and dual-task conditions.
AB  - Slow walking speed is strongly associated with adverse health outcomes, including
      cognitive impairment, in the older population. Moreover, adequate walking speed
      is crucial to maintain older pedestrians' mobility and safety in urban areas.
      This study aimed to identify the proportion of Swiss older adults that didn't
      reach 1.2 m/s, which reflects the requirements to cross streets within the green
      yellow phase of pedestrian lights, when walking fast under cognitive challenge. A
      convenience sample, including 120 older women (65%) and men, was recruited from
      the community (88%) and from senior residences and divided into groups of 70-79
      years (n = 59, 74.8 +/- 0.4 y; mean +/- SD) and >=80 years (n = 61, 85.5 +/- 0.5
      y). Steady state walking speed was assessed under single- and dual-task
      conditions at preferred and fast walking speed. Additionally, functional lower
      extremity strength (5-chair-rises test), subjective health rating, and
      retrospective estimates of fall frequency were recorded. Results showed that
      35.6% of the younger and 73.8% of the older participants were not able to walk
      faster than 1.2 m/s under the fast dual-task walking condition. Fast dual-task
      walking speed was higher compared to the preferred speed single- and dual-task
      conditions (all p < .05, r = .31 to .48). Average preferred single-task walking
      speed was 1.19 +/- 0.24 m/s (70-79 y) and 0.94 +/- 0.27 m/s (>=80 y),
      respectively, and correlated with performance in the 5-chair-rises test (rs = 
      .49, p < .001), subjective health (tau = .27, p < .001), and fall frequency (tau
      = -.23, p = .002). We conclude that the fitness status of many older people is
      inadequate to safely cross streets at pedestrian lights and maintain mobility in
      the community's daily life in urban areas. Consequently, training measures to
      improve the older population's cognitive and physical fitness should be promoted
      to enhance walking speed and safety of older pedestrians.

PMID- 28759588
TI  - Risk factors associated with the development of seizures among adult patients
      treated with ertapenem: A matched case-control study.
AB  - OBJECTIVE: The purpose of this study is to compare the characteristics of those
      ertapenem-treated adult patients with and without development of seizures, and
      identify the associated factors for the development of seizures. METHODS: This
      retrospective study was conducted at Chia-Yi Christian Hospital from January 2012
      to December 2014. Patients developing seizures during their ertapenem treatment
      course were identified as case patients. Those without seizures who had received
      ertapenem for at least five days were considered as the pool of control patients.
      For each case patient, four matched patients from the control pool were randomly
      selected as the final control group, based on age, gender, and the date of
      ertapenem prescription. RESULTS: A total of 1706 ertapenem-treated patients were
      identified, 33 (1.9%) individuals developed seizures with the enrollment of 132
      matched control patients. Among these 33 patients, the average age was 79.3 +/-
      7.5 years, and 20 (60.6%) were male. The mean Charlson co-morbidity score was 4.5
      +/- 2.4, and the first episode of seizure happened 3.3 +/- 2.6 days after
      receiving ertapenem. In multivariate logistic regression analysis, the
      independent predictors associated with the development of ertapenem-associated
      seizures were old stroke (OR, 14.36; 95% CI, 4.38-47.02; p < 0.0001), undergoing
      brain images within one year prior to the admission (OR, 5.73; 95% CI, 1.78
      18.43; p = 0.0034), low hemoglobin level (OR, 3.88; 95% CI, 1.28-12.75; p =
      0.0165) and low platelet count (OR, 4,94; 95% CI, 1.56-15.68; p = 0.0067) at
      presentations, and protective factors against the development of seizures were
      heart failure (OR, 0.04; 95% CI, 0.00-0.63; p = 0.0222), concomitant use of
      steroids (OR, 0.19; 95% CI, 0.05-0.77; p = 0.0201), or antiplatelet agents (OR,
      0.12; 95% CI, 0.02-0.63, p = 0.0123) with ertapenem. CONCLUSIONS: The development
      of ertapenem-associated seizures may occur more frequently and much earlier due
      to its widespread use in treating drug-resistant pathogens, especially when these
      pathogens emerged worldwide.Our study would help physician to estimate the risk
      of developing seizure among patients receiving ertapenem.

PMID- 28759589
TI  - Contour detection improved by context-adaptive surround suppression.
AB  - Recently, many image processing applications have taken advantage of a
      psychophysical and neurophysiological mechanism, called "surround suppression" to
      extract object contour from a natural scene. However, these traditional methods
      often adopt a single suppression model and a fixed input parameter called
      "inhibition level", which needs to be manually specified. To overcome these
      drawbacks, we propose a novel model, called "context-adaptive surround
      suppression", which can automatically control the effect of surround suppression
      according to image local contextual features measured by a surface estimator
      based on a local linear kernel. Moreover, a dynamic suppression method and its
      stopping mechanism are introduced to avoid manual intervention. The proposed
      algorithm is demonstrated and validated by a broad range of experimental results.

PMID- 28759591
TI  - Genome-wide diversity and differentiation in New World populations of the human
      malaria parasite Plasmodium vivax.
AB  - BACKGROUND: The Americas were the last continent colonized by humans carrying
      malaria parasites. Plasmodium falciparum from the New World shows very little
      genetic diversity and greater linkage disequilibrium, compared with its African
      counterparts, and is clearly subdivided into local, highly divergent populations.
      However, limited available data have revealed extensive genetic diversity in
      American populations of another major human malaria parasite, P. vivax. METHODS:
      We used an improved sample preparation strategy and next-generation sequencing to
      characterize 9 high-quality P. vivax genome sequences from northwestern Brazil.
      These new data were compared with publicly available sequences from recently
      sampled clinical P. vivax isolates from Brazil (BRA, total n = 11 sequences),
      Peru (PER, n = 23), Colombia (COL, n = 31), and Mexico (MEX, n = 19). PRINCIPAL
      FINDINGS/CONCLUSIONS: We found that New World populations of P. vivax are as
      diverse (nucleotide diversity pi between 5.2 * 10-4 and 6.2 * 10-4) as P. vivax
      populations from Southeast Asia, where malaria transmission is substantially more
      intense. They display several non-synonymous nucleotide substitutions (some of
      them previously undescribed) in genes known or suspected to be involved in
      antimalarial drug resistance, such as dhfr, dhps, mdr1, mrp1, and mrp-2, but not
      in the chloroquine resistance transporter ortholog (crt-o) gene. Moreover, P.
      vivax in the Americas is much less geographically substructured than local P.
      falciparum populations, with relatively little between-population genome-wide
      differentiation (pairwise FST values ranging between 0.025 and 0.092). Finally,
      P. vivax populations show a rapid decline in linkage disequilibrium with
      increasing distance between pairs of polymorphic sites, consistent with very
      frequent outcrossing. We hypothesize that the high diversity of present-day P.
      vivax lineages in the Americas originated from successive migratory waves and
      subsequent admixture between parasite lineages from geographically diverse sites.
      Further genome-wide analyses are required to test the demographic scenario
      suggested by our data.

PMID- 28759592
TI  - PCSF: An R-package for network-based interpretation of high-throughput data.
AB  - With the recent technological developments a vast amount of high-throughput data
      has been profiled to understand the mechanism of complex diseases. The current
      bioinformatics challenge is to interpret the data and underlying biology, where
      efficient algorithms for analyzing heterogeneous high-throughput data using
      biological networks are becoming increasingly valuable. In this paper, we propose
      a software package based on the Prize-collecting Steiner Forest graph
      optimization approach. The PCSF package performs fast and user-friendly network
      analysis of high-throughput data by mapping the data onto a biological networks
      such as protein-protein interaction, gene-gene interaction or any other
      correlation or coexpression based networks. Using the interaction networks as a
      template, it determines high-confidence subnetworks relevant to the data, which
      potentially leads to predictions of functional units. It also interactively
      visualizes the resulting subnetwork with functional enrichment analysis.

PMID- 28759590
TI  - Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in
      patients with active pulmonary tuberculosis from Tanzania.
AB  - Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic
      immune effector functions and are co-endemic in several regions of the world. We
      therefore hypothesized that helminth infection may influence Mtb-specific T-cell
      immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72
      individuals with pulmonary TB disease recruited from two Sub-Saharan regions with
      high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South
      Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional
      profile of TB patients from Tanzania are primarily composed of polyfunctional Th1
      and Th2 cells, associated with increased expression of Gata-3 and reduced
      expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of
      Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-gamma
      and dual IFN-gamma/TNF-alpha and associated with TB-induced systemic inflammation
      and elevated serum levels of type I IFNs. Of note, the proportion of patients
      with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co
      infected patients from TZ. It is likely that the underlying helminth infection
      and possibly genetic and other unknown environmental factors may have caused the
      induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ.
      Taken together, these results indicate that the generation of Mtb-specific CD4
      and CD8 T cell responses may be substantially influenced by environmental factors
      in vivo. These observations may have major impact in the identification of immune
      biomarkers of disease status and correlates of protection.

PMID- 28759594
TI  - Rapid discrimination of strain-dependent fermentation characteristics among
      Lactobacillus strains by NMR-based metabolomics of fermented vegetable juice.
AB  - In this study, we investigated the applicability of NMR-based metabolomics to
      discriminate strain-dependent fermentation characteristics of lactic acid
      bacteria (LAB), which are important microorganisms for fermented food production.
      To evaluate the discrimination capability, six type strains of Lactobacillus
      species and six additional L. brevis strains were used focusing on i) the
      difference between homo- and hetero-lactic fermentative species and ii) strain
      dependent characteristics within L. brevis. Based on the differences in the
      metabolite profiles of fermented vegetable juices, non-targeted principal
      component analysis (PCA) clearly separated the samples into those inoculated with
      homo- and hetero-lactic fermentative species. The separation was primarily
      explained by the different levels of dominant metabolites (lactic acid, acetic
      acid, ethanol, and mannitol). Orthogonal partial least squares discrimination
      analysis, based on a regions-of-interest (ROIs) approach, revealed the
      contribution of low-abundance metabolites: acetoin, phenyllactic acid, p
      hydroxyphenyllactic acid, glycerophosphocholine, and succinic acid for homolactic
      fermentation; and ornithine, tyramine, and gamma-aminobutyric acid (GABA) for
      heterolactic fermentation. Furthermore, ROIs-based PCA of seven L. brevis strains
      separated their strain-dependent fermentation characteristics primarily based on
      their ability to utilize sucrose and citric acid, and convert glutamic acid and
      tyrosine into GABA and tyramine, respectively. In conclusion, NMR metabolomics
      successfully discriminated the fermentation characteristics of the tested strains
      and provided further information on metabolites responsible for these
      characteristics, which may impact the taste, aroma, and functional properties of
      fermented foods.

PMID- 28759593
TI  - Proteogenomic analysis of the total and surface-exposed proteomes of Plasmodium
      vivax salivary gland sporozoites.
AB  - Plasmodium falciparum and Plasmodium vivax cause the majority of human malaria
      cases. Research efforts predominantly focus on P. falciparum because of the
      clinical severity of infection and associated mortality rates. However, P. vivax
      malaria affects more people in a wider global range. Furthermore, unlike P.
      falciparum, P. vivax can persist in the liver as dormant hypnozoites that can be
      activated weeks to years after primary infection, causing relapse of symptomatic
      blood stages. This feature makes P. vivax unique and difficult to eliminate with
      the standard tools of vector control and treatment of symptomatic blood stage
      infection with antimalarial drugs. Infection by Plasmodium is initiated by the
      mosquito-transmitted sporozoite stage, a highly motile invasive cell that targets
      hepatocytes in the liver. The most advanced malaria vaccine for P. falciparum
      (RTS,S, a subunit vaccine containing of a portion of the major sporozoite surface
      protein) conferred limited protection in Phase III trials, falling short of WHO
      established vaccine efficacy goals. However, blocking the sporozoite stage of
      infection in P. vivax, before the establishment of the chronic liver infection,
      might be an effective malaria vaccine strategy to reduce the occurrence of
      relapsing blood stages. It is also thought that a multivalent vaccine comprising
      multiple sporozoite surface antigens will provide better protection, but a
      comprehensive analysis of proteins in P. vivax sporozoites is not available. To
      inform sporozoite-based vaccine development, we employed mass spectrometry-based
      proteomics to identify nearly 2,000 proteins present in P. vivax salivary gland
      sporozoites. Analysis of protein post-translational modifications revealed
      extensive phosphorylation of glideosome proteins as well as regulators of
      transcription and translation. Additionally, the sporozoite surface proteins CSP
      and TRAP, which were recently discovered to be glycosylated in P. falciparum
      salivary gland sporozoites, were also observed to be similarly modified in P.
      vivax sporozoites. Quantitative comparison of the P. vivax and P. falciparum
      salivary gland sporozoite proteomes revealed a high degree of similarity in
      protein expression levels, including among invasion-related proteins.
      Nevertheless, orthologs with significantly different expression levels between
      the two species could be identified, as well as highly abundant, species-specific
      proteins with no known orthologs. Finally, we employed chemical labeling of live
      sporozoites to isolate and identify 36 proteins that are putatively surface
      exposed on P. vivax salivary gland sporozoites. In addition to identifying
      conserved sporozoite surface proteins identified by similar analyses of other
      Plasmodium species, our analysis identified several as-yet uncharacterized
      proteins, including a putative 6-Cys protein with no known ortholog in P.
      falciparum.

PMID- 28759595
TI  - HBV infection in untreated HIV-infected adults in Maputo, Mozambique.
AB  - BACKGROUND: HIV/ HBV coinfected patients are at high risk of developing chronic
      HBV infection, liver cirrhosis and hepatocellular carcinoma. In Mozambique, where
      HIV prevalence is one of the highest in the world, HIV-infected patients are
      scarcely characterized in terms of HBV coinfection and 3TC-resistance mutations
      profile. METHODS: To characterize ART-naive HIV-infected adults, with and without
      HBV coinfection, a cross-sectional study was conducted between May and November
      2012 in two health centers from Maputo city, Mozambique. Subjects were
      consecutively enrolled in the study and, then, tested for hepatitis B surface
      antigen (HBsAg). Moreover, CD4+ T cells count, HBV DNA in plasma, HBV genotyping
      and 3TC-resistance mutations profile of HBV were assessed in HIV/HBV coinfected
      patients. RESULTS: In total, 518 patients were enrolled in the study. The median
      age was 33 years old and 66.8% were women. The median CD4+ T cells count was 361
      cells/mm3 and 47 (9.1%) were coinfected with HBV. Out of 46 coinfected patients,
      24 (55.2%) had HBV DNA >= 20 - < 20 000 and 12 (26.1%) had HBV-DNA >=20 000. APRI
      > 2.0 was reported in 4.3% of coinfected and 1.7% of monoinfected patients (p =
      0.228), while FIB-4 > 3.25 was reported in 4.4% of coinfected and 1.3% of
      monoinfected patients (p = 0.112). Genotype A was the most frequent, identified
      in 25/27 (92.6%) patients, whereas genotype E was present in 2/27 (7.4%)
      patients. No patient had 3TC-resistance mutations. CONCLUSIONS: This study showed
      that HBV coinfection was prevalent among ART-naive HIV-infected adults in
      Mozambique. Overall, these data highlight the importance of screening HBV
      coinfection as an integrated measure of HIV routine care to improve health
      conditions and treatment of HIV/HBV coinfected patients.

PMID- 28759597
TI  - Objectively measured sedentary time among five ethnic groups in Amsterdam: The
      HELIUS study.
AB  - INTRODUCTION: Sedentary behaviour is increasingly recognised as a health risk.
      While differences in this behaviour might help explain ethnic differences in
      disease profiles, studies on sedentary behaviour in ethnic minorities are scarce.
      The aim of this study was to compare the levels and the socio-demographic and
      lifestyle-related correlates of objectively measured sedentary time among five
      ethnic groups in Amsterdam, the Netherlands. METHODS: Data were collected as part
      of the HELIUS study. The sample consisted of adults from a Dutch, Moroccan,
      African Surinamese, South-Asian Surinamese and Turkish ethnic origin. Data were
      collected by questionnaire, physical examination, and a combined heart rate and
      accelerometry monitor (Actiheart). Sedentary time was defined as waking time
      spent on activities of <1.5 metabolic equivalents. Ethnic differences in the
      levels of sedentary time were tested using ANOVA and ANCOVA analyses, while
      ethnic differences in the correlates of sedentary time were tested with
      interactions between ethnicity and potential correlates using general linear
      models. Associations between these correlates and sedentary time were explored
      using linear regression analyses stratified by ethnicity (pre-determined). All
      analyses were adjusted for gender and age. RESULTS: 447 participants were
      included in the analyses, ranging from 73 to 109 participants per ethnic group.
      Adjusted levels of sedentary time ranged from 569 minutes/day (9.5 hours/day) for
      participants with a Moroccan and Turkish origin to 621 minutes/day (10.3
      hours/day) in African Surinamese participants. There were no statistically
      significant differences in the levels or correlates of sedentary time between the
      ethnic groups. Meeting the physical activity recommendations (150 minutes/week)
      was consistently inversely associated with sedentary time across all ethnic
      groups, while age was positively associated with sedentary time in most groups.
      CONCLUSIONS: No statistically significant differences in the levels of
      objectively measured sedentary time or its socio-demographic and lifestyle
      related correlates were observed among five ethnic groups in Amsterdam, the
      Netherlands.

PMID- 28759596
TI  - Smokefree legislation effects on respiratory and sensory disorders: A systematic
      review and meta-analysis.
AB  - AIMS: The aim of this systematic review and meta-analysis is to synthesize the
      available evidence in scientific papers of smokefree legislation effects on
      respiratory diseases and sensory and respiratory symptoms (cough, phlegm, red
      eyes, runny nose) among all populations. MATERIALS AND METHODS: Systematic review
      and meta-analysis were carried out. A search between January 1995 and February
      2015 was performed in PubMed, EMBASE, Cochrane Library, Scopus, Web of Science,
      and Google Scholar databases. Inclusion criteria were: 1) original scientific
      studies about smokefree legislation, 2) Data before and after legislation were
      collected, and 3) Impact on respiratory and sensory outcomes were assessed.
      Paired reviewers independently carried out the screening of titles and abstracts,
      data extraction from full-text articles, and methodological quality assessment.
      RESULTS: A total number of 1606 papers were identified. 50 papers were selected,
      26 were related to symptoms (23 concerned workers). Most outcomes presented
      significant decreases in the percentage of people suffering from them, especially
      in locations with comprehensive measures and during the immediate post-ban period
      (within the first six months). Four (50%) of the papers concerning pulmonary
      function reported some significant improvement in expiratory parameters.
      Significant decreases were described in 13 of the 17 papers evaluating asthma
      hospital admissions, and there were fewer significant reductions in chronic
      obstructive pulmonary disease admissions (range 1-36%) than for asthma (5-31%).
      Six studies regarding different respiratory diseases showed discrepant results,
      and four papers about mortality reported significant declines in subgroups. Low
      bias risk was present in 23 (46%) of the studies. CONCLUSIONS: Smokefree
      legislation appears to improve respiratory and sensory symptoms at short term in
      workers (the overall effect being greater in comprehensive smokefree legislation
      in sensory symptoms) and, to a lesser degree, rates of hospitalization for
      asthma.

PMID- 28759598
TI  - Nurse in limbo: A qualitative study of nursing in disasters in Iranian context.
AB  - BACKGROUND: An understanding of nurses' experiences in disasters can help to
      identify their problems in this area. These can be overcome with better planning
      and preparation. The aim of this study was to explore the experiences and
      perceptions of disaster nurses regarding their provision of disaster health care
      services. METHODS: This was a qualitative study using an inductive qualitative
      content analysis. Participants included 15 Iranian nurses who had experiences of
      health care delivery in disasters. A purposeful sampling was applied until data
      saturation was reached. Data were collected using semi-structured interviews and
      then analyzed based on the principle of inductive content analysis. RESULTS: Five
      main categories emerged from the experiences and perceptions of nurses who were
      involved in providing health care services in disasters: afraid of probability of
      recurrence, necessity of providing healthcare services for an unknown period of
      time, challenge of what to prioritize, nurses' own conflicting emotions, and
      their concern for their own families. DISCUSSION: There are several factors
      affecting the delivery of healthcare in disasters. Nurses, who feel better
      prepared and have some understanding of the ethical implications of working under
      different standards of care, may be more comfortable with care giving in
      disasters. Appropriately, training and preparing nurses for disasters is
      important for optimizing the safe functioning and minimizing emotional and
      psychological damage.

PMID- 28759599
TI  - The risk of new-onset diabetes in antidepressant users - A systematic review and
      meta-analysis.
AB  - BACKGROUND: Antidepressant Drugs (ADs) are among the most commonly prescribed
      medications in developed countries. The available epidemiological evidence
      suggests an association between AD use and higher risk of developing type 2
      diabetes mellitus. However, some methodological issues make the interpretation of
      these results difficult. Moreover, very recent studies provided conflicting
      results. Given the high prevalence of both diabetes and AD use in many countries,
      clarifying whether this association is causal is of extreme relevance for the
      public health. The aim of the present study is to provide an up-to-date
      evaluation of the evidence in support of a causal role of ADs in inducing
      diabetes. METHODS AND FINDINGS: A systematic literature search was conducted to
      identify relevant studies in MEDLINE (PubMed), PsycINFO, and International
      Pharmaceutical Abstracts (IPA) through 31st December 2016. Only studies assessing
      the incidence of new-onset diabetes in subjects treated with ADs were included.
      Results were pooled using a random-effects meta-analysis. Moreover, we
      extensively reviewed the role of the different sources of bias that have been
      proposed to explain the association between AD and diabetes. Twenty studies met
      the inclusion criteria. In the meta-analysis, the association between AD use and
      diabetes was still evident after the inclusion of the recent negative studies
      [pooled relative risk = 1.27, 95% confidence interval (CI), 1.19-1.35; p<0.001].
      None of the biases proposed by previous authors seemed able to fully explain the
      observed association. CONCLUSIONS: This updated meta-analysis confirms the
      association between AD use and incident diabetes. It still remains a matter of
      debate whether single ADs exert a different effect on the risk of diabetes. Given
      the possible heterogeneity, we suggest that a classification of ADs according to
      their pharmacological profiles could be useful in better elucidating the nature
      of this association.

PMID- 28759600
TI  - Anatomic tunnel placement can be achieved with a modification to transtibial
      technique in single bundle anterior cruciate ligament reconstruction: A cadaver
      study.
AB  - Placing the tunnels in the anatomic positions is important for successful
      restoration of knee function after anterior cruciate ligament reconstruction
      (ACLR). It has been shown that it is difficult to place the tunnels in the
      anatomic position using the transtibial technique. The purpose of this study was
      to evaluate the effect of each step of our modified transtibial technique (mTT)
      on the positioning of the femoral tunnel so as to assess whether the mTT could
      achieve anatomic placements of the tunnels without tibial tunnel expansion. Ten
      fresh-frozen cadaveric knees were used. First, the tibial tunnel was created in
      the center of ACL footprint. Then, a pin was inserted through the tibial tunnel
      using a femoral guide by four stepwise techniques: transtibial technique,
      additional anterior drawer force applied to the proximal tibia, another
      additional varus force applied to the tibia and finally, additional external
      rotation of the tibia and the femoral guide (mTT). Then, tibial tunnel was re
      reamed using mTT with 10mm-diameter reamer. The pin positions in each technique
      on the femur were evaluated by the quadrant method and shapes of the tibial
      tunnel apertures were evaluated. Femoral pin positions in the four techniques
      were 23.6+/-4.5%, 28.4+/-3.4%, 30.1+/-3.8%, 33.2+/-4.5% in the superior-inferior
      position, and 23.9+/-4.3%, 26.2+/-3.7%, 32.0+/-4.3%, 36.9+/-4.8% in the anterior
      posterior position, respectively. Pin position shifted to more inferior and
      posterior position with each step of mTT (all p values comparing superior
      inferior and anterior-posterior positions of each step with positions of previous
      step were 0.008 or less). Using mTT, tibial tunnel aperture was 10.5+/-0.3mm wide
      and 12.9+/-1.1mm long. In conclusion, anatomic placements of femoral tunnels in
      ACLR without excessive tibial tunnel expansion could be achieved using the mTT.

PMID- 28759601
TI  - Prevalence of Toxocara species infection in the U.S.: Results from the National
      Health and Nutrition Examination Survey, 2011-2014.
AB  - Toxocariasis is one of the most common neglected infections of poverty in the
      U.S. with a reported National Health and Nutrition Examination Survey (NHANES)
      III (1988-1994) seroprevalence of 13.9% based on enzyme immunoassay testing. We
      reviewed NHANES data from 2011-2014 to assess current levels. Sera collected from
      NHANES 2011-2014 participants six years and older were tested for exposure using
      rTc-CTL-1 antigen, a more sensitive and specific recombinant antigen for IgG
      antibodies for Toxocara spp. These results were subdivided into children (age 6
      17) and adults (age >= 18) and then compared between various sociodemographic
      characteristics. Given prior associations of Toxocara exposure with atopic
      disease and lead exposure, we also reviewed laboratory values including complete
      blood counts and blood and urine lead levels. Data from 13,509 individuals with
      Toxocara antibody results were examined including 3337 children (15.2%) and 10172
      adults (84.8%). Overall seroprevalence was 5.1%. In adults increased antibody
      positivity occurred with non-White ethnicity, male gender, less than college
      level education and lower income. Among children, increased antibody positivity
      was solely related to a lack of health insurance. Additionally, seropositivity
      was associated with increased blood lead and eosinophil levels in adults and both
      blood and urine lead levels in children. Relative to NHANES III (1988-1994),
      current data suggest an overall decrease in Toxocara spp. seroprevalence from
      13.9% to 5.1%, however this may be artificially lowered due to difference in
      testing methods used. Persistent disparities appear to be associated with at-risk
      populations such as minority ethnicity and low socioeconomic status.

PMID- 28759602
TI  - Risk factors for inadequate antibody response to primary rabies vaccination in
      dogs under one year of age.
AB  - Ensuring the adequacy of response to rabies vaccination in dogs is important,
      particularly in the context of pet travel. Few studies have examined the factors
      associated with dogs' failure to achieve an adequate antibody titer after
      vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs
      after primary vaccination. Dogs under one year of age whose serum was submitted
      to a reference laboratory for routine diagnostics, and which had no prior
      documented history of vaccination were enrolled (n = 8,011). Geometric mean
      titers (GMT) were calculated and univariate analysis was performed to assess
      factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16
      weeks of age had a significantly higher GMT compared to dogs vaccinated at a
      younger age (1.64 IU/ml, 1.57-1.72, ANOVA p < 0.01). There was no statistical
      difference in GMT between dogs vaccinated <12 weeks and dogs vaccinated 12-16
      weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an
      adequate titer within the first 3 days of primary vaccination; failure rates were
      also high if the interval from vaccination to titer check was greater than 90
      days. Over 90% of dogs that failed primary vaccination were able to achieve
      adequate titers after booster vaccination. The ideal timing for blood draw is 8
      30 days after primary vaccination. In the event of a failure, most dogs will
      achieve an adequate serologic response upon a repeat titer (in the absence of
      booster vaccination). Booster vaccination after failure provided the highest
      probability of an acceptable titer.

PMID- 28759603
TI  - The isokinetic strength profile of elite soccer players according to playing
      position.
AB  - The aim of this study was to compare isokinetic strength performance profiles in
      elite soccer players across different field positions. A total of 111 elite
      international players of Polish Ekstraklasa (the top division in Poland) were
      examined during the 2010-2015 seasons. The players were classified into six
      positional roles: central defenders (CD), external defenders (ED), central
      midfielders (CM), external midfielders (EM), forwards (F), and goalkeepers (G).
      The concentric isokinetic strength (peak torque [PT] of quadriceps and
      hamstrings, H/Q ratios) was calculated for the dominant leg and the non-dominant
      leg at angular velocity of 1.05 rad .s-1, whereas to assess isokinetic muscle
      endurance, the total work [TW] at angular velocity of 4.19 rad .s-1, was taken
      into consideration. The results showed that isokinetic strength performance
      varies significantly among players in different playing positions. The analysis
      of PT for quadriceps (PT-Q) and hamstrings (PT-H) generally showed that the
      goalkeepers and central midfielders had lower strength levels compared to other
      playing positions. In the case of PT-H and hamstring/quadricep (H/Q) peak torque
      ratios, statistically significant differences were also noted for the legs, where
      mean values noted for the dominant leg were higher than for the non-dominant leg.
      For TW for quadriceps (TW-Q) and hamstrings (TW-H), statistically significant
      differences were noted only between playing positions. TW-Q values for
      goalkeepers were lower than for central defenders and external midfielders. TW-H
      values for goalkeepers were lower than for central midfielders, central defenders
      and external midfielders. This study showed that specific functional activity of
      players in individual positions on the field influences the varied profile of
      isokinetic strength performance.

PMID- 28759604
TI  - A web-based tool to predict acute kidney injury in patients with ST-elevation
      myocardial infarction: Development, internal validation and comparison.
AB  - BACKGROUND: In ST-elevation myocardial infarction (STEMI), acute kidney injury
      (AKI) may increase subsequent morbidity and mortality. Still, it remains
      difficult to predict AKI risk in these patients. We sought to 1) determine the
      frequency and clinical outcomes of AKI and, 2) develop, validate and compare a
      web-based tool for predicting AKI. METHODS & FINDINGS: In a racially diverse
      series of 1144 consecutive STEMI patients, Stage 1 or greater AKI occurred in
      12.9% and was severe (Stage 2-3) in 2.9%. AKI was associated with increased
      mortality (5.7-fold, unadjusted) and hospital stay (2.5-fold). AKI was associated
      with systolic dysfunction, increased left ventricular end-diastolic pressures,
      hypotension and intra-aortic balloon counterpulsation. A computational algorithm
      (UT-AKI) was derived and internally validated. It showed higher sensitivity and
      improved overall prediction for AKI (area under the curve 0.76) vs. other
      published indices. Higher UT-AKI scores were associated with more severe AKI,
      longer hospital stay and greater hospital mortality. CONCLUSIONS: In a large,
      racially diverse cohort of STEMI patients, Stage 1 or greater AKI was relatively
      common and was associated with significant morbidity and mortality. A web
      accessible, internally validated tool was developed with improved overall value
      for predicting AKI. By identifying patients at increased risk, this tool may help
      physicians tailor post-procedural diagnostic and therapeutic strategies after
      STEMI to reduce AKI and its associated morbidity and mortality.

PMID- 28759605
TI  - THPdb: Database of FDA-approved peptide and protein therapeutics.
AB  - THPdb (http://crdd.osdd.net/raghava/thpdb/) is a manually curated repository of
      Food and Drug Administration (FDA) approved therapeutic peptides and proteins.
      The information in THPdb has been compiled from 985 research publications, 70
      patents and other resources like DrugBank. The current version of the database
      holds a total of 852 entries, providing comprehensive information on 239 US-FDA
      approved therapeutic peptides and proteins and their 380 drug variants. The
      information on each peptide and protein includes their sequences, chemical
      properties, composition, disease area, mode of activity, physical appearance,
      category or pharmacological class, pharmacodynamics, route of administration,
      toxicity, target of activity, etc. In addition, we have annotated the structure
      of most of the protein and peptides. A number of user-friendly tools have been
      integrated to facilitate easy browsing and data analysis. To assist scientific
      community, a web interface and mobile App have also been developed.

PMID- 28759606
TI  - Spaced education in medical residents: An electronic intervention to improve
      competency and retention of medical knowledge.
AB  - BACKGROUND: Spaced education is a novel method that improves medical education
      through online repetition of core principles often paired with multiple-choice
      questions. This model is a proven teaching tool for medical students, but its
      effect on resident learning is less established. We hypothesized that repetition
      of key clinical concepts in a "Clinical Pearls" format would improve knowledge
      retention in medical residents. METHODS: This study investigated spaced education
      with particular emphasis on using a novel, email-based reinforcement program, and
      a randomized, self-matched design, in which residents were quizzed on medical
      knowledge that was either reinforced or not with electronically-administered
      spaced education. Both reinforced and non-reinforced knowledge was later tested
      with four quizzes. RESULTS: Overall, respondents incorrectly answered 395 of 1008
      questions (0.39; 95% CI, 0.36-0.42). Incorrect response rates varied by quiz
      (range 0.34-0.49; p = 0.02), but not significantly by post-graduate year (PGY1
      0.44, PGY2 0.33, PGY3 0.38; p = 0.08). Although there was no evidence of benefit
      among residents (RR = 1.01; 95% CI, 0.83-1.22; p = 0.95), we observed a
      significantly lower risk of incorrect responses to reinforced material among
      interns (RR = 0.83, 95% CI, 0.70-0.99, p = 0.04). CONCLUSIONS: Overall,
      repetition of Clinical Pearls did not statistically improve test scores amongst
      junior and senior residents. However, among interns, repetition of the Clinical
      Pearls was associated with significantly higher test scores, perhaps reflecting
      their greater attendance at didactic sessions and engagement with Clinical
      Pearls. Although the study was limited by a low response rate, we employed test
      and control questions within the same quiz, limiting the potential for selection
      bias. Further work is needed to determine the optimal spacing and content load of
      Clinical Pearls to maximize retention amongst medical residents. This particular
      protocol of spaced education, however, was unique and readily reproducible
      suggesting its potential efficacy for intern education within a large residency
      program.

PMID- 28759607
TI  - Comparison of soil sampling and analytical methods for asbestos at the Sumas
      Mountain Asbestos Site-Working towards a toolbox for better assessment.
AB  - Established soil sampling methods for asbestos are inadequate to support risk
      assessment and risk-based decision making at Superfund sites due to difficulties
      in detecting asbestos at low concentrations and difficulty in extrapolating soil
      concentrations to air concentrations. Environmental Protection Agency (EPA)'s
      Office of Land and Emergency Management (OLEM) currently recommends the rigorous
      process of Activity Based Sampling (ABS) to characterize site exposures. The
      purpose of this study was to compare three soil analytical methods and two soil
      sampling methods to determine whether one method, or combination of methods,
      would yield more reliable soil asbestos data than other methods. Samples were
      collected using both traditional discrete ("grab") samples and incremental
      sampling methodology (ISM). Analyses were conducted using polarized light
      microscopy (PLM), transmission electron microscopy (TEM) methods or a combination
      of these two methods. Data show that the fluidized bed asbestos segregator (FBAS)
      followed by TEM analysis could detect asbestos at locations that were not
      detected using other analytical methods; however, this method exhibited high
      relative standard deviations, indicating the results may be more variable than
      other soil asbestos methods. The comparison of samples collected using ISM versus
      discrete techniques for asbestos resulted in no clear conclusions regarding
      preferred sampling method. However, analytical results for metals clearly showed
      that measured concentrations in ISM samples were less variable than discrete
      samples.

PMID- 28759608
TI  - Survival and gene expression under different temperature and humidity regimes in
      ants.
AB  - Short term variation in environmental conditions requires individuals to adapt
      via changes in behavior and/or physiology. In particular variation in temperature
      and humidity are common, and the physiological adaptation to changes in
      temperature and humidity often involves alterations in gene expression, in
      particular that of heat-shock proteins. However, not only traits involved in the
      resistance to environmental stresses, but also other traits, such as immune
      defenses, may be influenced indirectly by changes in temperature and humidity.
      Here we investigated the response of the ant F. exsecta to two temperature
      regimes (20 degrees C & 25 degrees C), and two humidity regimes (50% & 75%), for
      two populations. We measured the survival and the expression of six metabolism-
      and immunity-related genes, and furthermore compared the expression levels in
      each condition with the pre-experiment expression levels. Both populations
      survived equally well at the two humidities, but one population showed higher
      mortality at 25 degrees C than 20 degrees , at 50% humidity. Similarly, the two
      populations showed striking differences in their gene expression before the
      experiment, and in their responses to the environmental conditions. Surprisingly,
      instead of converging to similar expression levels in the same environmental
      conditions, gene expression diverged further apart. This indicates different
      reaction norms to both temperature and humidity for the two populations.
      Furthermore, our results suggest that also immune defenses are indirectly
      affected by environmental conditions.

PMID- 28759609
TI  - Knockout of the gamma subunit of the AP-1 adaptor complex in the human parasite
      Trypanosoma cruzi impairs infectivity and differentiation and prevents the
      maturation and targeting of the major protease cruzipain.
AB  - The AP-1 Adaptor Complex assists clathrin-coated vesicle assembly in the trans
      Golgi network (TGN) of eukaryotic cells. However, the role of AP-1 in the
      protozoan Trypanosoma cruzi-the Chagas disease parasite-has not been addressed.
      Here, we studied the function and localization of AP-1 in different T. cruzi life
      cycle forms, by generating a gene knockout of the large AP-1 subunit gamma
      adaptin (TcAP1-gamma), and raising a monoclonal antibody against TcAP1-gamma. Co
      localization with a Golgi marker and with the clathrin light chain showed that
      TcAP1-gamma is located in the Golgi, and it may interact with clathrin in vivo,
      at the TGN. Epimastigote (insect form) parasites lacking TcAP1-gamma (TcgammaKO)
      have reduced proliferation and differentiation into infective metacyclic
      trypomastigotes (compared with wild-type parasites). TcgammaKO parasites have
      also displayed significantly reduced infectivity towards mammalian cells.
      Importantly, TcAP1-gamma knockout impaired maturation and transport to lysosome
      related organelles (reservosomes) of a key cargo-the major cysteine protease
      cruzipain, which is important for parasite nutrition, differentiation and
      infection. In conclusion, the defective processing and transport of cruzipain
      upon AP-1 ablation may underlie the phenotype of TcgammaKO parasites.

PMID- 28759610
TI  - Transcriptome analysis of the tea oil camellia (Camellia oleifera) reveals
      candidate drought stress genes.
AB  - BACKGROUND: The tea-oil camellia (Camellia oleifera) is the most important oil
      plant in southern China, and has a strong resistance to drought and barren soil.
      Understanding the molecular mechanisms of drought tolerance would greatly promote
      its cultivation and molecular breeding. RESULTS: In total, we obtained 76,585
      unigenes with an average length of 810 bp and an N50 of 1,092 bp. We mapped all
      the unigenes to the NCBI 'nr' (non-redundant), SwissProt, KEGG, and clusters of
      orthologous groups (COG) databases, where 52,531 (68.6%) unigenes were
      functionally annotated. According to the annotation, 46,171 (60.8%) unigenes
      belong to 338 KEGG pathways. We identified a series of unigenes that are related
      to the synthesis and regulation of abscisic acid (ABA), the activity of
      protective enzymes, vitamin B6 metabolism, the metabolism of osmolytes, and
      pathways related to the biosynthesis of secondary metabolites. After exposed to
      drought for 12 hours, the number of differentially-expressed genes (DEGs) between
      treated plants and control plants increased in the G4 cultivar, while there was
      no significant increase in the drought-tolerant C3 cultivar. DEGs associated with
      drought stress responsive pathways were identified by KEGG pathway enrichment
      analysis. Moreover, we found 789 DEGs related to transcription factors. Finally,
      according to the results of qRT-PCR, the expression levels of the 20 unigenes
      tested were consistent with the results of next-generation sequencing.
      CONCLUSIONS: In the present study, we identified a large set of cDNA unigenes
      from C. oleifera annotated using public databases. Further studies of DEGs
      involved in metabolic pathways related to drought stress and transcription will
      facilitate the discovery of novel genes involved in resistance to drought stress
      in this commercially important plant.

PMID- 28759611
TI  - TPL-2 restricts Ccl24-dependent immunity to Heligmosomoides polygyrus.
AB  - TPL-2 (COT, MAP3K8) kinase activates the MEK1/2-ERK1/2 MAPK signaling pathway in
      innate immune responses following TLR, TNFR1 and IL-1R stimulation. TPL-2
      contributes to type-1/Th17-mediated autoimmunity and control of intracellular
      pathogens. We recently demonstrated TPL-2 reduces severe airway allergy to house
      dust mite by negatively regulating type-2 responses. In the present study, we
      found that TPL-2 deficiency resulted in resistance to Heligmosomoides polygyrus
      infection, with accelerated worm expulsion, reduced fecal egg burden and reduced
      worm fitness. Using co-housing experiments, we found resistance to infection in
      TPL-2 deficient mice (Map3k8-/-) was independent of microbiota alterations in H.
      polygyrus infected WT and Map3k8-/-mice. Additionally, our data demonstrated
      immunity to H. polygyrus infection in TPL-2 deficient mice was not due to
      dysregulated type-2 immune responses. Genome-wide analysis of intestinal tissue
      from infected TPL-2-deficient mice identified elevated expression of genes
      involved in chemotaxis and homing of leukocytes and cells, including Ccl24 and
      alternatively activated genes. Indeed, Map3k8-/-mice had a significant influx of
      eosinophils, neutrophils, monocytes and Il4GFP+ T cells. Conditional knockout
      experiments demonstrated that specific deletion of TPL-2 in CD11c+ cells, but not
      Villin+ epithelial cells, LysM+ myeloid cells or CD4+ T cells, led to accelerated
      resistance to H. polygyrus. In line with a central role of CD11c+ cells, CD11c+
      CD11b+ cells isolated from TPL-2-deficient mice had elevated Ccl24. Finally,
      Ccl24 neutralization in TPL-2 deficient mice significantly decreased the
      expression of Arg1, Retnla, Chil3 and Ear11 correlating with a loss of resistance
      to H. polygyrus. These observations suggest that TPL-2-regulated Ccl24 in
      CD11c+CD11b+ cells prevents accelerated type-2 mediated immunity to H. polygyrus.
      Collectively, this study identifies a previously unappreciated role for TPL-2
      controlling immune responses to H. polygyrus infection by restricting Ccl24
      production.

PMID- 28759612
TI  - Scheduling rules for patients with diabetes mellitus that facilitate split-dosing
      improve the quality of bowel preparation for colonoscopy.
AB  - BACKGROUND & AIMS: An adequate bowel preparation for colonoscopy is best achieved
      by giving the cleansing regimen as a split-dose with the second dose given 4-6
      hours before the procedure. This can be difficult to administer to diabetics who
      are preferentially scheduled for early morning procedures. We examined the impact
      on bowel preparation quality of scheduling diabetics for mid-morning (9:30 am or
      later) procedures rather than early morning procedures (7:30-9:00 AM) to
      facilitate a split-dose preparation. METHODS: Historical cohort study of 34,415
      patients (1,805 diabetics) age 18-74 years without significant comorbidities who
      underwent an outpatient colorectal cancer screening-related colonoscopy either
      before (2013) or after (2014) a unit wide change in scheduling practices for
      diabetics. The primary outcome was the rate of inadequate bowel preparation.
      Secondary outcomes include the rate of procedures complete to the cecum,
      procedure duration and detection rates of polyps, any colorectal cancer screening
      relevant lesion (adenoma, sessile serrated adenoma, large proximal hyperplastic
      polyp) and advanced adenomas. RESULTS: From 2013 to 2014, the proportion of
      diabetics with an inadequate bowel preparation decreased from 7.7% to 3.2% (95%
      confidence interval for the difference 2.2%-6.8%, P<0.00005). There was no
      significant change in the proportion of non-diabetics with inadequate preparation
      (2% in both years). There was no change in secondary outcomes in diabetics from
      2013 to 2014. CONCLUSIONS: Preferentially scheduling diabetic patients later in
      the morning that more conveniently allowed for a split dose bowel preparation
      resulted in decreased rates of inadequate bowel preparation without
      disadvantaging other patients.

PMID- 28759613
TI  - Acute phase proteins as prospective risk markers for arterial stiffness: The
      Malmo Diet and Cancer cohort.
AB  - BACKGROUND AND OBJECTIVES: Arterial stiffness plays a significant role in the
      development and progression of adverse cardiovascular events and all-cause
      mortality. This observational study aims to explore the relationship between six
      acute phase proteins namely, ceruloplasmin, alpha-1-antitrypsin, orosomucoid,
      haptoglobin, complement C3 and C-reactive protein (CRP), and carotid-femoral
      pulse wave velocity (c-f PWV) in a population-based cohort, and to also explore
      the effect of low-grade inflammation on the relationship between diabetes and c-f
      PWV. METHOD: The study consisted of participants from the Malmo Diet and Cancer
      study with data from baseline examinations (1991-1994) and follow-up examinations
      (2007-2012). Arterial stiffness was measured at follow-up by determining c-f PWV.
      After excluding participants with missing data, the total study population
      included 2338 subjects. General linear models were used to assess the
      relationship between baseline acute phase proteins and c-f PWV. RESULTS: After
      adjusting for traditional risk factors the participants in the 4th quartile vs
      1st quartile of alpha-1-antitrypsin (geometric mean: 10.32 m/s vs 10.04 m/s)
      (p<0.05), C3 (10.35 m/s vs 10.06 m/s) (p<0.05) and CRP (10.37 m/s vs 9.96 m/s)
      (p<0.001) showed significant association with c-f PWV. Diabetes at follow-up was
      also associated with high c-f PWV, however, this relationship was independent of
      low grade inflammation. CONCLUSION: Alpha-1-antitrypsin, C3 and CRP are
      associated with arterial stiffness. The results indicate that low grade
      inflammation is associated with arterial stiffness in addition to established
      cardiovascular risk factors.

PMID- 28759614
TI  - Pilot study of a novel classroom designed to prevent myopia by increasing
      children's exposure to outdoor light.
AB  - We sought to assess light characteristics and user acceptability of a prototype
      Bright Classroom (BC), designed to prevent children's myopia by exposing them to
      light conditions resembling the outdoors. Conditions were measured throughout the
      school year in the glass-constructed BC, a traditional classroom (TC) and
      outdoors. Teachers and children completed user questionnaires, and children rated
      reading comfort at different light intensities. A total of 230 children (mean age
      10.2 years, 57.4% boys) and 13 teachers (36.8 years, 15.4% men) completed
      questionnaires. The median (Inter Quartile Range) light intensity in the BC
      (2,540 [1,330-4,060] lux) was greater than the TC (477 [245-738] lux, P < 0.001),
      though less than outdoors (19,500 [8,960-36,000] lux, P < 0.001). A prominent
      spectral peak at 490-560 nm was present in the BC and outdoors, but less so in
      the TC. Teachers and children gave higher overall ratings to the BC than TC, and
      light intensity in the BC in summer and on sunny days (>5,000 lux) was at the
      upper limit of children's comfort for reading. In summary, light intensity in the
      BC exceeds TC, and is at the practical upper limit for routine use. Children and
      teachers prefer the BC.

PMID- 28759615
TI  - Enhanced smartcard-based password-authenticated key agreement using extended
      chaotic maps.
AB  - A smartcard based password-authenticated key agreement scheme enables a legal
      user to log in to a remote authentication server and access remote services
      through public networks using a weak password and a smart card. Lin recently
      presented an improved chaotic maps-based password-authenticated key agreement
      scheme that used smartcards to eliminate the weaknesses of the scheme of Guo and
      Chang, which does not provide strong user anonymity and violates session key
      security. However, the improved scheme of Lin does not exhibit the freshness
      property and the validity of messages so it still fails to withstand denial-of
      service and privileged-insider attacks. Additionally, a single malicious
      participant can predetermine the session key such that the improved scheme does
      not exhibit the contributory property of key agreements. This investigation
      discusses these weaknesses and proposes an enhanced smartcard-based password
      authenticated key agreement scheme that utilizes extended chaotic maps. The
      session security of this enhanced scheme is based on the extended chaotic map
      based Diffie-Hellman problem, and is proven in the real-or-random and the
      sequence of games models. Moreover, the enhanced scheme ensures the freshness of
      communicating messages by appending timestamps, and thereby avoids the weaknesses
      in previous schemes.

PMID- 28759617
TI  - Flow and fracture behavior of aluminum alloy 6082-T6 at different tensile strain
      rates and triaxialities.
AB  - This study aims to investigate the flow and fracture behavior of aluminum alloy
      6082-T6 (AA6082-T6) at different strain rates and triaxialities. Two groups of
      Charpy impact tests were carried out to further investigate its dynamic impact
      fracture property. A series of tensile tests and numerical simulations based on
      finite element analysis (FEA) were performed. Experimental data on smooth
      specimens under various strain rates ranging from 0.0001~3400 s-1 shows that
      AA6082-T6 is rather insensitive to strain rates in general. However, clear rate
      sensitivity was observed in the range of 0.001~1 s-1 while such a characteristic
      is counteracted by the adiabatic heating of specimens under high strain rates. A
      Johnson-Cook constitutive model was proposed based on tensile tests at different
      strain rates. In this study, the average stress triaxiality and equivalent
      plastic strain at facture obtained from numerical simulations were used for the
      calibration of J-C fracture model. Both of the J-C constitutive model and
      fracture model were employed in numerical simulations and the results was
      compared with experimental results. The calibrated J-C fracture model exhibits
      higher accuracy than the J-C fracture model obtained by the common method in
      predicting the fracture behavior of AA6082-T6. Finally, the Scanning Electron
      Microscope (SEM) of fractured specimens with different initial stress
      triaxialities were analyzed. The magnified fractographs indicate that high
      initial stress triaxiality likely results in dimple fracture.

PMID- 28759616
TI  - Altered nicotine reward-associated behavior following alpha4 nAChR subunit
      deletion in ventral midbrain.
AB  - Nicotinic acetylcholine receptors containing alpha4 subunits (alpha4beta2*
      nAChRs) are critical for nicotinic cholinergic transmission and the addictive
      action of nicotine. To identify specific activities of these receptors in the
      adult mouse brain, we coupled targeted deletion of alpha4 nAChR subunits with
      behavioral and and electrophysiological measures of nicotine sensitivity. A viral
      mediated Cre/lox approach allowed us to delete alpha4 from ventral midbrain (vMB)
      neurons. We used two behavioral assays commonly used to assess the motivational
      effects of drugs of abuse: home-cage oral self-administration, and place
      conditioning. Mice lacking alpha4 subunits in vMB consumed significantly more
      nicotine at the highest offered nicotine concentration (200 MUg/mL) compared to
      control mice. Deletion of alpha4 subunits in vMB blocked nicotine-induced
      conditioned place preference (CPP) without affecting locomotor activity.
      Acetylcholine-evoked currents as well as nicotine-mediated increases in synaptic
      potentiation were reduced in mice lacking alpha4 in vMB. Immunostaining verified
      that alpha4 subunits were deleted from both dopamine and non-dopamine neurons in
      the ventral tegmental area (VTA). These results reveal that attenuation of
      alpha4* nAChR function in reward-related brain circuitry of adult animals may
      increase nicotine intake by enhancing the rewarding effects and/or reducing the
      aversive effects of nicotine.

PMID- 28759618
TI  - Prevalence and predictors of hypovitaminosis D among the elderly in subtropical
      region.
AB  - The prevalence of low vitamin D status in the elderly population of subtropical
      area and the potential risk/protective factors have not been addressed. This
      cross-sectional questionnaire-based study, which collected
      demographic/anthropometric data and information on diet habit and sun exposure,
      recruited 170 subjects with mean age 70.9+/-5.6 in rural areas of southern
      Taiwan. Serum 25-OH vitamin D, calcium, and intact parathyroid hormone were also
      measured. Using cut-off level of 30 ng/mL, subjects were divided into low (n =
      95) and normal (n = 75) serum vitamin D groups. The results demonstrated a low
      vitamin D status in 30.6% of men and 57.7% of women. Dietary vitamin D intake was
      another factor associated with vitamin D status (p = 0.02). Logistic regression
      identified inadequate intake of vitamin D-rich food as the only risk factor for
      low vitamin D status in men (OR = 4.55, p = 0.01), whereas inadequate sun
      exposure was the only predictable risk with dose-response relationship in women
      (low vs. high sun exposure, OR = 6.84, p = 0.018; moderate vs. high sun exposure,
      OR = 6.67, p = 0.005). In conclusion, low vitamin D status was common in the
      elderly of subtropical rural areas. Low sun exposure and inadequate dietary
      vitamin D consumption were associated with a low vitamin D status in females and
      males, respectively.

PMID- 28759619
TI  - FMRI to probe sex-related differences in brain function with multitasking.
AB  - BACKGROUND: Although established as a general notion in society, there is no
      solid scientific foundation for the existence of sex-differences in multitasking.
      Reaction time and accuracy in dual task conditions have an inverse relationship
      relative to single task, independently from sex. While a more disseminated
      network, parallel to decreasing accuracy and reaction time has been demonstrated
      in dual task fMRI studies, little is known so far whether there exist respective
      sex-related differences in activation. METHODS: We subjected 20 women (mean age =
      25.45; SD = 5.23) and 20 men (mean age = 27.55; SD = 4.00) to a combined verbal
      and spatial fMRI paradigm at 3.0T to assess sex-related skills, based on the
      assumption that generally women better perform in verbal tasks while men do
      better in spatial tasks. We also obtained behavioral tests for verbal and spatial
      intelligence, attention, executive functions, and working memory. RESULTS: No
      differences between women and men were observed in behavioral measures of dual
      tasking or cognitive performance. Generally, brain activation increased with
      higher task load, mainly in the bilateral inferior and prefrontal gyri, the
      anterior cingulum, thalamus, putamen and occipital areas. Comparing sexes, women
      showed increased activation in the inferior frontal gyrus in the verbal dual-task
      while men demonstrated increased activation in the precuneus and adjacent visual
      areas in the spatial task. CONCLUSION: Against the background of equal cognitive
      and behavioral dual-task performance in both sexes, we provide first evidence for
      sex-related activation differences in functional networks for verbal and spatial
      dual-tasking.

PMID- 28759620
TI  - Prevalence of pulmonary tuberculosis among prison inmates: A cross-sectional
      survey at the Correctional and Detention Facility of Abidjan, Cote d'Ivoire.
AB  - BACKGROUND: In Cote d'Ivoire, a TB prison program has been developed since 1999.
      This program includes offering TB screening to prisoners who show up with TB
      symptoms at the infirmary. Our objective was to estimate the prevalence of
      pulmonary TB among inmates at the Correctional and Detention Facility of Abidjan,
      the largest prison of Cote d'Ivoire, 16 years after this TB program was
      implemented. METHODS: Between March and September 2015, inmates, were screened
      for pulmonary TB using systematic direct smear microscopy, culture and chest X
      ray. All participants were also proposed HIV testing. TB was defined as either
      confirmed (positive culture), probable (positive microscopy and/or chest X-ray
      findings suggestive of TB) or possible (signs or symptoms suggestive of TB, no X
      Ray or microbiological evidence). Factors associated with confirmed tuberculosis
      were analysed using multivariable logistic regression. RESULTS: Among the 943
      inmates screened, 88 (9.3%) met the TB case definition, including 19 (2.0%) with
      confirmed TB, 40 (4.2%) with probable TB and 29 (3.1%) with possible TB. Of the
      19 isolated TB strains, 10 (53%) were TB drug resistant, including 7 (37%) with
      multi-resistance. Of the 10 patients with TB resistant strain, only one had a
      past history of TB treatment. HIV prevalence was 3.1% overall, and 9.6%among TB
      cases. Factors associated with confirmed TB were age >=30 years (Odds Ratio 3.8;
      95% CI 1.1-13.3), prolonged cough (Odds Ratio 3.6; 95% CI 1.3-9.5) and fever
      (Odds Ratio 2.7; 95% CI 1.0-7.5). CONCLUSION: In the country largest prison,
      pulmonary TB is still 10 (confirmed) to 44 times (confirmed, probable or
      possible) as frequent as in the Cote d'Ivoire general population, despite a long
      time running symptom-based program of TB detection. Decreasing TB prevalence and
      limiting the risk of MDR may require the implementation of annual in-cell TB
      screening campaigns that systematically target all prison inmates.

PMID- 28759621
TI  - Identification of novel antibody-reactive detection sites for comprehensive
      gluten monitoring.
AB  - Certain cereals like wheat, rye or barley contain gluten, a protein mixture that
      can trigger celiac disease (CD). To make gluten-free diets available for affected
      individuals the gluten content of foodstuff must be monitored. For this purpose,
      antibody-based assays exist which rely on the recognition of certain linear
      gluten sequence motifs. Yet, not all CD-active gluten constituents and fragments
      formed during food processing/fermentation may be covered by those tests. In this
      study, we therefore assayed the coverage of reportedly CD-active gluten
      components by currently available detection antibodies and determined the
      antibody-inducing capacity of wheat gluten constituents in order to provide novel
      diagnostic targets for comprehensive gluten quantitation. Immunizations of
      outbred mice with purified gliadins and glutenins were conducted and the linear
      target recognition profile of the sera was recorded using synthetic peptide
      arrays that covered the sequence space of gluten constituents present in those
      preparations. The resulting murine immunorecognition profile of gluten
      demonstrated that further linear binding sites beyond those recognized by the
      monoclonal antibodies alpha20, R5 and G12 exist and may be exploitable as
      diagnostic targets. We conclude that the safety of foodstuffs for CD patients can
      be further improved by complementing current tests with antibodies directed
      against additional CD-active gluten components. Currently unrepresented linear
      gluten detection sites in glutenins and alpha-gliadins suggest sequences QQQYPS,
      PQQSFP, QPGQGQQG and QQPPFS as novel targets for antibody generation.

PMID- 28759622
TI  - Contamination with HIV antibody may be responsible for false positive results in
      specimens tested on automated platforms running HIV 4th generation assays in a
      region of high HIV prevalence.
AB  - INTRODUCTION: In South Africa where the prevalence of HIV infection is very high,
      4th generation HIV antibody/p24 antigen combo immunoassays are the tests of
      choice for laboratory based screening. Testing is usually performed in clinical
      pathology laboratories on automated analysers. To investigate the cause of false
      positive results on 4th generation HIV testing platforms in public sector
      laboratories, the performance of two automated platforms was compared in a
      clinical pathology setting, firstly on routine diagnostic specimens and secondly
      on known sero-negative samples. METHODS: Firstly, 1181 routine diagnostic
      specimens were sequentially tested on Siemens and Roche automated 4th generation
      platforms. HIV viral load, western blot and follow up testing were used to
      determine the true status of inconclusive specimens. Subsequently, known HIV
      seronegative samples from a single donor were repeatedly tested on both platforms
      and an analyser was tested for surface contamination with HIV positive serum to
      identify how suspected specimen contamination could be occurring. RESULTS: Serial
      testing of diagnostic specimens yielded 163 weakly positive or discordant
      results. Only 3 of 163 were conclusively shown to indicate true HIV infection.
      Specimen contamination with HIV antibody was suspected, based on the following
      evidence: the proportion of positive specimens increased on repeated passage
      through the analysers; viral loads were low or undetectable and western blots
      negative or indeterminate on problem specimens; screen negative, 2nd test
      positive specimens tested positive when reanalysed on the screening assay; follow
      up specimens (where available) were negative. Similarly, an increasing number of
      known negative specimens became (repeatedly) sero-positive on serial passage
      through one of the analysers. Internal and external analyser surfaces were
      contaminated with HIV serum, evidence that sample splashes occur during testing.
      CONCLUSIONS: Due to the extreme sensitivity of these assays, contamination with
      minute amounts of HIV antibody can cause a negative sample to test positive.
      Better contamination control measures are needed on analysers used in clinical
      pathology environments, especially in regions where HIV sero-prevalence is high.

PMID- 28759623
TI  - Spatial modelling of contribution of individual level risk factors for mortality
      from Middle East respiratory syndrome coronavirus in the Arabian Peninsula.
AB  - BACKGROUND: Middle East respiratory syndrome coronavirus is a contagious
      respiratory pathogen that is contracted via close contact with an infected
      subject. Transmission of the pathogen has occurred through animal-to-human
      contact at first followed by human-to-human contact within families and health
      care facilities. DATA AND METHODS: This study is based on a retrospective
      analysis of the Middle East respiratory syndrome coronavirus outbreak in the
      Kingdom of Saudi Arabia between June 2012 and July 2015. A Geoadditive variable
      model for binary outcomes was applied to account for both individual level risk
      factors as well spatial variation via a fully Bayesian approach. RESULTS: Out of
      959 confirmed cases, 642 (67%) were males and 317 (33%) had died. Three hundred
      and sixty four (38%) cases occurred in Ar Riyad province, while 325 (34%) cases
      occurred in Makkah. Individuals with some comorbidity had a significantly higher
      likelihood of dying from MERS-CoV compared with those who did not suffer
      comorbidity [Odds ratio (OR) = 2.071; 95% confidence interval (CI): 1.307,
      3.263]. Health-care workers were significantly less likely to die from the
      disease compared with non-health workers [OR = 0.372, 95% CI: 0.151, 0.827].
      Patients who had fatal clinical experience and those with clinical and
      subclinical experiences were equally less likely to die from the disease compared
      with patients who did not have fatal clinical experience and those without
      clinical and subclinical experiences respectively. The odds of dying from the
      disease was found to increase as age increased beyond 25 years and was much
      higher for individuals with any underlying comorbidities. CONCLUSION:
      Interventions to minimize mortality from the Middle East respiratory syndrome
      coronavirus should particularly focus individuals with comorbidity, non-health
      care workers, patients with no clinical fatal experience, and patients without
      any clinical and subclinical experiences.

PMID- 28759624
TI  - Fear, opposition, ambivalence, and omission: Results from a follow-up study on
      unmet need for family planning in Ghana.
AB  - INTRODUCTION: Despite a relatively strong family planning program and regionally
      modest levels of fertility, Ghana recorded one of the highest levels of unmet
      need for family planning on the African continent in 2008. Unmet need for family
      planning is a composite measure based on apparent contradictions between women's
      reproductive preferences and practices. Women who want to space or limit births
      but are not using contraception are considered to have an unmet need for family
      planning. The study sought to understand the reasons behind high levels of unmet
      need for family planning in Ghana. METHODS: A mixed methods follow-up study was
      embedded within the stratified, two-stage cluster sample of the 2014 Ghana
      Demographic and Health Survey (GDHS). Women in 13 survey clusters who were
      identified as having unmet need, along with a reference group of current family
      planning users, were approached to be reinterviewed within an average of three
      weeks from their GDHS interview. Follow-up respondents were asked a combination
      of closed- and open-ended questions about fertility preferences and contraceptive
      use. Closed-ended responses were compared against the original survey;
      transcripts were thematically coded and analyzed using qualitative analysis
      software. RESULTS: Among fecund women identified by the 2014 GDHS as having unmet
      need, follow-up interviews revealed substantial underreporting of method use,
      particularly traditional methods. Complete postpartum abstinence was sometimes
      the intended method of family planning but was overlooked during questions about
      method use. Other respondents classified as having unmet need had ambivalent
      fertility preferences. In several cases, respondents expressed revised fertility
      preferences upon follow-up that would have made them ineligible for inclusion in
      the unmet need category. The reference group of family planning users also
      expressed unstable fertility preferences. Aversion to modern method use was
      generally more substantial than reported in the GDHS, particularly the risk of
      menstrual side effects, personal or partner opposition to family planning, and
      religious opposition to contraception.

PMID- 28759625
TI  - Combination therapy with ampicillin and azithromycin improved outcomes in a mouse
      model of group B streptococcal sepsis.
AB  - BACKGROUND: Evidence suggests that beta-lactam monotherapy of streptococcal
      infections may incite stronger inflammation and is inferior to combination
      therapy with macrolides. We hypothesized that use of macrolides alone or in
      combination with a beta-lactam for group B streptococcal (GBS) sepsis would
      improve outcomes by reducing inflammation. METHODS: TNF-alpha was measured from
      supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four
      treatment regimens: ampicillin alone, azithromycin alone, or combination of
      azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated
      with same four regimens. Clinical sepsis scores were monitored; serum cytokines
      (TNF-alpha, IL-6, IL-10) and chemokines (MIP-1alpha) were measured at the end.
      RESULTS: GBS isolates exposed to azithromycin or combination (compared to
      ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis
      model, mortality was lower along with decreased sepsis scores in mice treated
      with combination therapy. Mean serum IL-6 was lower in mice treated with
      azithromycin alone (66+/-52 pg/ml) or combination of ampicillin plus azithromycin
      (52+/-22 pg/ml) compared to ampicillin alone (260+/-160 pg/ml) (p<0.005).
      CONCLUSIONS: Combination therapy of ampicillin+azithromycin improved outcomes in
      a murine GBS sepsis model; this therapeutic approach deserves additional study.

PMID- 28759626
TI  - Glutamate/GABA+ ratio is associated with the psychosocial domain of autistic and
      schizotypal traits.
AB  - BACKGROUND: The autism and schizophrenia spectra overlap to a large degree in the
      social and interpersonal domains. Similarly, abnormal excitatory glutamate and
      inhibitory gamma-aminobutyric acid (GABA) neurotransmitter concentrations have
      been reported for both spectra, with the interplay of these neurotransmitters
      important for cortical excitation to inhibition regulation. This study
      investigates whether these neurotransmitter abnormalities are specific to the
      shared symptomatology, and whether the degree of abnormality increases with
      increasing symptom severity. Hence, the relationship between the glutamate/GABA
      ratio and autism and schizophrenia spectrum traits in an unmedicated, subclinical
      population was investigated. METHODS: A total of 37 adults (19 female, 18 male)
      aged 18-38 years completed the Autism Spectrum Quotient (AQ) and Schizotypal
      Personality Questionnaire (SPQ), and participated in the resting state proton
      magnetic resonance spectroscopy study in which sequences specific for
      quantification of glutamate and GABA+ concentration were applied to a right and
      left superior temporal voxel. RESULTS: There were significant, moderate, positive
      relationships between right superior temporal glutamate/GABA+ ratio and AQ, SPQ
      and AQ+SPQ total scores (p<0.05), SPQ subscales Social Anxiety, No Close Friend,
      Constricted Affect, Odd Behaviour, Odd Speech, Ideas of Reference and
      Suspiciousness, and AQ subscales Social Skills, Communication and Attention
      Switching (p<0.05); increased glutamate/GABA+ coinciding with higher scores on
      these subscales. Only the relationships between glutamate/GABA+ ratio and Social
      Anxiety, Constricted Affect, Social Skills and Communication survived multiple
      comparison correction (p< 0.004). Left superior temporal glutamate/GABA+ ratio
      reduced with increasing restricted imagination (p<0.05). CONCLUSION: These
      findings demonstrate evidence for an association between excitatory/inhibitory
      neurotransmitter concentrations and symptoms that are shared between the autism
      and schizophrenia spectra.

PMID- 28759627
TI  - Increased risk of dental trauma in patients with allergic rhinitis: A nationwide
      population-based cohort study.
AB  - Allergic rhinitis (AR) is associated with various developmental issues that
      affecting dentition. We aimed to determine whether AR is associated with an
      increased risk of traumatic dental injuries (TDIs) in Taiwanese individuals. We
      used the Taiwan National Health Insurance Research Database (NHIRD) to conduct a
      nested case-control study. We compared an AR cohort with a matched cohort of
      patients without AR. New TDI cases were determined during our study period. To
      compare TDI risk between our study cohorts, we used Cox proportional regression
      analysis, and hazard ratios (HR) with 95% confidence intervals (CI) were
      calculated to quantify the association between AR exposure and TDI risk. In
      total, 76749 patients with AR (31715 male; 45034 female) were identified. In the
      AR and the non-AR cohorts, 312 patients in total had TDI. Patients with AR had a
      significantly higher risk of TDI than those without AR (aHR = 1.92; 95% CI =
      1.459-2.525; P < 0.001). The risk of TDI was markedly higher in the AR cohort,
      except in the 3-12-year-old group, and with a CCI >= 1. AR patients had a future
      risk of TDI, indicating a potentially linked disease pathophysiology. The
      association between AR and TDI is greater among general patients. Clinicians and
      caregivers should be aware of potential TDI co-morbidity in patients with AR.

PMID- 28759628
TI  - "What else are you worried about?" - Integrating textual responses into
      quantitative social science research.
AB  - Open-ended questions have routinely been included in large-scale survey and panel
      studies, yet there is some perplexity about how to actually incorporate the
      answers to such questions into quantitative social science research. Tools
      developed recently in the domain of natural language processing offer a wide
      range of options for the automated analysis of such textual data, but their
      implementation has lagged behind. In this study, we demonstrate straightforward
      procedures that can be applied to process and analyze textual data for the
      purposes of quantitative social science research. Using more than 35,000 textual
      answers to the question "What else are you worried about?" from participants of
      the German Socio-economic Panel Study (SOEP), we (1) analyzed characteristics of
      respondents that determined whether they answered the open-ended question, (2)
      used the textual data to detect relevant topics that were reported by the
      respondents, and (3) linked the features of the respondents to the worries they
      reported in their textual data. The potential uses as well as the limitations of
      the automated analysis of textual data are discussed.

PMID- 28759629
TI  - Genetic and morphological analyses of Gracilaria firma and G. changii
      (Gracilariaceae, Rhodophyta), the commercially important agarophytes in western
      Pacific.
AB  - Many studies classifying Gracilaria species for the exploitation of agarophytes
      and the development of the agar industry were conducted before the prevalence of
      molecular tools, resulting in the description of many species based solely on
      their morphology. Gracilaria firma and G. changii are among the commercially
      important agarophytes from the western Pacific; both feature branches with basal
      constrictions that taper toward acute apices. In this study, we contrasted the
      morpho-anatomical circumscriptions of the two traditionally described species
      with molecular data from samples that included representatives of G. changii
      collected from its type locality. Concerted molecular analyses using the rbcL and
      cox1 gene sequences, coupled with morphological observations of the collections
      from the western Pacific, revealed no inherent differences to support the
      treatment of the two entities as distinct taxa. We propose merging G. changii (a
      later synonym) into G. firma and recognize G. firma based on thallus branches
      with abrupt basal constrictions that gradually taper toward acute (or sometimes
      broken) apices, cystocarps consisting of small gonimoblast cells and
      inconspicuous multinucleate tubular nutritive cells issuing from gonimoblasts
      extending into the inner pericarp at the cystocarp floor, as well as deep
      spermatangial conceptacles of the verrucosa-type. The validation of specimens
      under different names as a single genetic species is useful to allow
      communication and knowledge transfer among groups from different fields. This
      study also revealed considerably low number of haplotypes and nucleotide
      diversity with apparent phylogeographic patterns for G. firma in the region.
      Populations from the Philippines and Taiwan were divergent from each other as
      well as from the populations from Malaysia, Thailand, Singapore and Vietnam.
      Establishment of baseline data on the genetic diversity of this commercially
      important agarophyte is relevant in the context of cultivation, as limited
      genetic diversity may jeopardize the potential for its genetic improvement over
      time.

PMID- 28759630
TI  - C77G in PTPRC (CD45) is no risk allele for ovarian cancer, but associated with
      less aggressive disease.
AB  - The pan lymphocyte marker CD45 exists in various isoforms arising from
      alternative splicing of the exons 4, 5 and 6. While naive T cells express CD45RA
      translated from an mRNA containing exon 4, exons 4-6 are spliced out to encode
      the shorter CD45R0 in antigen-experienced effector/memory T cells. The SNP C77G
      (rs17612648) is located in exon 4 and blocks the exon's differential splicing
      from the pre-mRNA, enforcing expression of CD45RA. Several studies have linked
      C77G to autoimmune diseases but lack of validation in other cohorts has left its
      role elusive. An incidental finding in an ovarian cancer patient cohort from West
      Norway (Bergen region, n = 312), suggested that the frequency of C77G was higher
      among ovarian cancer patients than in healthy Norwegians (n = 1,357) (3.0% vs.
      1.8% allele frequency). However, this finding could not be validated in a larger
      patient cohort from South-East Norway (Oslo region, n = 1,198) with 1.2% allele
      frequency. Hence, C77G is not associated with ovarian cancer in the Norwegian
      population. However, its frequency was increased in patients with FIGO stage II,
      endometrioid histology or an age at diagnosis of 60 years or older indicating a
      possible association with a less aggressive cancer type.

PMID- 28759631
TI  - Physical and cognitive effort discounting across different reward magnitudes:
      Tests of discounting models.
AB  - The effort required to obtain a rewarding outcome is an important factor in
      decision-making. Describing the reward devaluation by increasing effort intensity
      is substantial to understanding human preferences, because every action and
      choice that we make is in itself effortful. To investigate how reward valuation
      is affected by physical and cognitive effort, we compared mathematical
      discounting functions derived from research on discounting. Seven discounting
      models were tested across three different reward magnitudes. To test the models,
      data were collected from a total of 114 participants recruited from the general
      population. For one-parameter models (hyperbolic, exponential, and parabolic),
      the data were explained best by the exponential model as given by a percentage of
      explained variance. However, after introducing an additional parameter, data
      obtained in the cognitive and physical effort conditions were best described by
      the power function model. Further analysis, using the second order Akaike and
      Bayesian Information Criteria, which account for model complexity, allowed us to
      identify the best model among all tested. We found that the power function best
      described the data, which corresponds to conventional analyses based on the R2
      measure. This supports the conclusion that the function best describing reward
      devaluation by physical and cognitive effort is a concave one and is different
      from those that describe delay or probability discounting. In addition,
      consistent magnitude effects were observed that correspond to those in delay
      discounting research.

PMID- 28759632
TI  - Significant liver fibrosis assessed using liver transient elastography is
      independently associated with low bone mineral density in patients with non
      alcoholic fatty liver disease.
AB  - BACKGROUND: Metabolic bone disorders frequently occur in patients with chronic
      liver disease; however, the association between liver fibrosis and bone mineral
      density in patients with non-alcoholic fatty liver disease (NAFLD) is unclear.
      METHODS: This is a cross-sectional analysis of 231 asymptomatic subjects (160
      women, 61.6 years old) from a university hospital setting, between February 2012
      and December 2014. Bone mineral density (BMD) was measured at the lumbar spine,
      femur neck, and total hip using dual-energy X-ray absorptiometry (DXA). Liver
      fibrosis and steatosis were assessed using transient elastography. RESULTS: Among
      a total of 231 individuals, 129 subjects (55.8%) had NAFLD. BMDs at lumbar spine,
      femur neck, and total hip were significantly lower in patients having NAFLD with
      significant fibrosis, compared with patients having NAFLD without significant
      fibrosis (Ps<0.005). In patients with NAFLD, significant liver fibrosis revealed
      marked negative correlations with BMD at the lumber spine (r = -0.19, P = 0.032),
      femur neck (r = -0.19, P = 0.034), and total hip (r = -0.21, P = 0.016). A
      multivariate linear regression analysis revealed that significant liver fibrosis
      was independently correlated with low BMD at the femur neck (beta = -0.18, P =
      0.039) and total hip (beta = -0.21, P = 0.005) after adjustment for age, sex,
      BMI, fasting plasma glucose, alanine aminotransferase, high-density lipoprotein
      cholesterol, and liver steatosis among patients with NAFLD. Using multivariable
      logistic regression, significant liver fibrosis was independently associated with
      overall osteopenia and osteoporosis in subjects having NAFLD (OR = 4.10, 95% CI =
      1.02-16.45). CONCLUSION: The presence of significant liver fibrosis assessed via
      TE was independently associated with low BMD in NAFLD subjects.

PMID- 28759633
TI  - Dictionary learning based noisy image super-resolution via distance penalty
      weight model.
AB  - In this study, we address the problem of noisy image super-resolution. Noisy low
      resolution (LR) image is always obtained in applications, while most of the
      existing algorithms assume that the LR image is noise-free. As to this situation,
      we present an algorithm for noisy image super-resolution which can achieve
      simultaneously image super-resolution and denoising. And in the training stage of
      our method, LR example images are noise-free. For different input LR images, even
      if the noise variance varies, the dictionary pair does not need to be retrained.
      For the input LR image patch, the corresponding high resolution (HR) image patch
      is reconstructed through weighted average of similar HR example patches. To
      reduce computational cost, we use the atoms of learned sparse dictionary as the
      examples instead of original example patches. We proposed a distance penalty
      model for calculating the weight, which can complete a second selection on
      similar atoms at the same time. Moreover, LR example patches removed mean pixel
      value are also used to learn dictionary rather than just their gradient features.
      Based on this, we can reconstruct initial estimated HR image and denoised LR
      image. Combined with iterative back projection, the two reconstructed images are
      applied to obtain final estimated HR image. We validate our algorithm on natural
      images and compared with the previously reported algorithms. Experimental results
      show that our proposed method performs better noise robustness.

PMID- 28759634
TI  - The role of co-opted ESCRT proteins and lipid factors in protection of
      tombusviral double-stranded RNA replication intermediate against reconstituted
      RNAi in yeast.
AB  - Reconstituted antiviral defense pathway in surrogate host yeast is used as an
      intracellular probe to further our understanding of virus-host interactions and
      the role of co-opted host factors in formation of membrane-bound viral replicase
      complexes in protection of the viral RNA against ribonucleases. The inhibitory
      effect of the RNA interference (RNAi) machinery of S. castellii, which only
      consists of the two-component DCR1 and AGO1 genes, was measured against tomato
      bushy stunt virus (TBSV) in wild type and mutant yeasts. We show that deletion of
      the co-opted ESCRT-I (endosomal sorting complexes required for transport I) or
      ESCRT-III factors makes TBSV replication more sensitive to the RNAi machinery in
      yeast. Moreover, the lack of these pro-viral cellular factors in cell-free
      extracts (CFEs) used for in vitro assembly of the TBSV replicase results in
      destruction of dsRNA replication intermediate by a ribonuclease at the 60 min
      time point when the CFE from wt yeast has provided protection for dsRNA. In
      addition, we demonstrate that co-opted oxysterol-binding proteins and membrane
      contact sites, which are involved in enrichment of sterols within the tombusvirus
      replication compartment, are required for protection of viral dsRNA. We also show
      that phosphatidylethanolamine level influences the formation of RNAi-resistant
      replication compartment. In the absence of peroxisomes in pex3Delta yeast, TBSV
      subverts the ER membranes, which provide as good protection for TBSV dsRNA
      against RNAi or ribonucleases as the peroxisomal membranes in wt yeast.
      Altogether, these results demonstrate that co-opted protein factors and usurped
      lipids are exploited by tombusviruses to build protective subcellular environment
      against the RNAi machinery and possibly other cellular ribonucleases.

PMID- 28759635
TI  - Intolerance of uncertainty in opioid dependency - Relationship with trait anxiety
      and impulsivity.
AB  - Intolerance of uncertainty (IU) is the tendency to interpret ambiguous situations
      as threatening and having negative consequences, resulting in feelings of
      distress and anxiety. IU has been linked to a number of anxiety disorders, and
      anxiety felt in the face of uncertainty may result in maladaptive behaviors such
      as impulsive decision making. Although there is strong evidence that anxiety and
      impulsivity are risk factors for addiction, there is a paucity of research
      examining the role of IU in this disorder. The rate of opioid addiction, in
      particular, has been rising steadily in recent years, which necessitates deeper
      understanding of risk factors in order to develop effective prevention and
      treatment methods. The current study tested for the first time whether opioid
      dependent adults are less tolerant of uncertainty compared to a healthy
      comparison group. Opioid dependent patients undergoing methadone maintenance
      therapy (n = 114) and healthy comparisons (n = 69) completed the following
      scales: Intolerance of Uncertainty Scale, the Barrett Impulsivity Scale, and the
      State Trait Anxiety Inventory. Analysis revealed that these measures were
      positively correlated with each other and that opioid-dependent patients had
      significantly higher IU scores. Regression analysis revealed that anxiety
      mediated the relationship between IU and impulsivity. Hierarchical moderation
      regression found an interaction between addiction status and impulsivity on IU
      scores in that the relationship between these variables was only observed in the
      patient group. Findings suggest that IU is a feature of addiction but does not
      necessarily play a unique role. Further research is needed to explore the complex
      relationship between traits and how they may contribute to the development and
      maintenance of addiction.

PMID- 28759636
TI  - ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by
      hypothermia.
AB  - BACKGROUND: Malignant gliomas are highly invasive, difficult to treat, and
      account for 2% of cancer deaths worldwide. Glioblastoma Multiforme (GBM)
      comprises the most common and aggressive intracranial tumor. The study hypothesis
      is to investigate the modification of Photodynamic Therapy (PDT) efficacy by mild
      hypothermia leads to increased glioma cell kill while protecting normal neuronal
      structures. METHODS: Photosensitizer accumulation and PDT efficacy in vitro were
      quantified in various glioma cell lines, primary rat neurons, and astrocytes. In
      vivo studies were carried out in healthy brain and RG2 glioma of naive Fischer
      rats. Hypothermia was induced at 1 hour pre- to 2 hours post-PDT, with ALA-PpIX
      accumulation and PDT treatments effects on tumor and normal brain PDT quantified
      using optical spectroscopy, histology, immunohistochemistry, MRI, and survival
      studies, respectively. FINDINGS: In vitro studies demonstrated significantly
      improved post-PDT survival in primary rat neuronal cells. Rat in vivo studies
      confirmed a neuroprotective effect to hypothermia following PpIX mediated PDT by
      T2 mapping at day 10, reflecting edema/inflammation volume reduction. Mild
      hypothermia increased PpIX fluorescence in tumors five-fold, and the median post
      PDT rat survival time (8.5 days normothermia; 14 days hypothermia). Histology and
      immunohistochemistry show close to complete cellular protection in normal brain
      structures under hypothermia. CONCLUSIONS: The benefits of hypothermia on both
      normal neuronal tissue as well as increased PpIX fluorescence and RG2 induced rat
      survival strongly suggest a role for hypothermia in photonics-based surgical
      techniques, and that a hypothermic intervention could lead to considerable
      patient outcome improvements.

PMID- 28759638
TI  - Influence of the microwave technology on solid dispersions of mefenamic acid and
      flufenamic acid.
AB  - The present studies were undertaken to develop solvent-free solid dispersions
      (SDs) for poorly soluble anti-inflammatory drugs mefenamic acid (MA) and
      flufenamic acid (FFA) in order to enhance their in vitro dissolution rate and in
      vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using
      microwaves irradiation (MW) technique. Different carriers such as Pluronic
      F127(r) (PL), Eudragit EPO(r) (EPO), polyethylene glycol 4000 (PEG 4000) and
      Gelucire 50/13 (GLU) were used for the preparation of SDs. Prepared MW irradiated
      SDs were characterized physicochemically using differential scanning calorimetry
      (DSC), thermogravimetric analysis (TGA), Fourier transform infra-red (FT-IR)
      spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy
      (SEM). The physicochemical characteristics and drug release profile of SDs were
      compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed
      that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was
      remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and
      FFA prepared using PEG 400 showed higher drug release profile in comparison with
      those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and
      FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were
      also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The
      results showed significant % inhibition by MA-PEG (87.74% after 4 h) and FFA-PEG
      SDs (81.76% after 4 h) in comparison with pure MA (68.09% after 4 h) and pure FFA
      (55.27% after 4 h) (P<0.05). These results suggested that MW irradiated SDs of MA
      and FFA could be successfully used for the enhancement of in vitro dissolution
      rate and in vivo therapeutic efficacy of both drugs.

PMID- 28759637
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) in zebrafish models of
      nephrotic syndrome.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is an inhibitor of
      megakaryopoiesis and platelet function. Recently, PACAP deficiency was observed
      in children with nephrotic syndrome (NS), associated with increased platelet
      count and aggregability and increased risk of thrombosis. To further study PACAP
      deficiency in NS, we used transgenic Tg(cd41:EGFP) zebrafish with GFP-labeled
      thrombocytes. We generated two models for congenital NS, a morpholino injected
      model targeting nphs1 (nephrin), which is mutated in the Finnish-type congenital
      NS. The second model was induced by exposure to the nephrotoxic compound
      adriamycin. Nephrin RNA expression was quantified and zebrafish embryos were live
      screened for proteinuria and pericardial edema as evidence of renal impairment.
      Protein levels of PACAP and its binding-protein ceruloplasmin were measured and
      GFP-labeled thrombocytes were quantified. We also evaluated the effects of PACAP
      morpholino injection and the rescue effects of PACAP-38 peptide in both
      congenital NS models. Nephrin downregulation and pericardial edema were observed
      in both nephrin morpholino injected and adriamycin exposed congenital NS models.
      However, PACAP deficiency was demonstrated only in the adriamycin exposed
      condition. Ceruloplasmin levels and the number of GFP-labeled thrombocytes
      remained unchanged in both models. PACAP morpholino injections worsened survival
      rates and the edema phenotype in both congenital NS models while injection with
      human PACAP-38 could only rescue the adriamycin exposed model. We hereby report,
      for the first time, PACAP deficiency in a NS zebrafish model as a consequence of
      adriamycin exposure. However, distinct from the human congenital NS, both
      zebrafish models retained normal levels of ceruloplasmin and thrombocytes. We
      further extend the renoprotective effects of the PACAP-38 peptide against
      adriamycin toxicity in zebrafish.

PMID- 28759639
TI  - G protein-coupled receptor kinase 2 promotes cardiac hypertrophy.
AB  - The increase in protein activity and upregulation of G-protein coupled receptor
      kinase 2 (GRK2) is a hallmark of cardiac stress and heart failure. Inhibition of
      GRK2 improved cardiac function and survival and diminished cardiac remodeling in
      various animal heart failure models. The aim of the present study was to
      investigate the effects of GRK2 on cardiac hypertrophy and dissect potential
      molecular mechanisms. In mice we observed increased GRK2 mRNA and protein levels
      following transverse aortic constriction (TAC). Conditional GRK2 knockout mice
      showed attenuated hypertrophic response with preserved ventricular geometry 6
      weeks after TAC operation compared to wild-type animals. In isolated neonatal rat
      ventricular cardiac myocytes stimulation with angiotensin II and phenylephrine
      enhanced GRK2 expression leading to enhanced signaling via protein kinase B (PKB
      or Akt), consecutively inhibiting glycogen synthase kinase 3 beta (GSK3beta),
      such promoting nuclear accumulation and activation of nuclear factor of activated
      T-cells (NFAT). Cardiac myocyte hypertrophy induced by in vitro GRK2
      overexpression increased the cytosolic interaction of GRK2 and phosphoinositide 3
      kinase gamma (PI3Kgamma). Moreover, inhibition of PI3Kgamma as well as GRK2 knock
      down prevented Akt activation resulting in halted NFAT activity and reduced
      cardiac myocyte hypertrophy. Our data show that enhanced GRK2 expression triggers
      cardiac hypertrophy by GRK2-PI3Kgamma mediated Akt phosphorylation and subsequent
      inactivation of GSK3beta, resulting in enhanced NFAT activity.

PMID- 28759640
TI  - T-dependent B cell responses to Plasmodium induce antibodies that form a high
      avidity multivalent complex with the circumsporozoite protein.
AB  - The repeat region of the Plasmodium falciparum circumsporozoite protein (CSP) is
      a major vaccine antigen because it can be targeted by parasite neutralizing
      antibodies; however, little is known about this interaction. We used isothermal
      titration calorimetry, X-ray crystallography and mutagenesis-validated modeling
      to analyze the binding of a murine neutralizing antibody to Plasmodium falciparum
      CSP. Strikingly, we found that the repeat region of CSP is bound by multiple
      antibodies. This repeating pattern allows multiple weak interactions of single
      FAB domains to accumulate and yield a complex with a dissociation constant in the
      low nM range. Because the CSP protein can potentially cross-link multiple B cell
      receptors (BCRs) we hypothesized that the B cell response might be T cell
      independent. However, while there was a modest response in mice deficient in T
      cell help, the bulk of the response was T cell dependent. By sequencing the BCRs
      of CSP-repeat specific B cells in inbred mice we found that these cells underwent
      somatic hypermutation and affinity maturation indicative of a T-dependent
      response. Last, we found that the BCR repertoire of responding B cells was
      limited suggesting that the structural simplicity of the repeat may limit the
      breadth of the immune response.

PMID- 28759641
TI  - Novel sensitive monoclonal antibody based competitive enzyme-linked immunosorbent
      assay for the detection of raw and processed bovine beta-casein.
AB  - Cow milk protein allergy (CMPA) is the most common childhood food allergy, which
      can sometimes persist or can newly develop in adulthood with severe symptoms.
      CMPA's treatment is complete dietary avoidance of milk proteins. To achieve this
      task, patients have to be aware of milk proteins found as "hidden allergens" in
      food commodities. In regard to milk proteins, it has been reported that
      allergenicity of caseins remains unaffected upon heat treatment. For these
      reasons, we aimed to obtain monoclonal antibodies (mAbs) against native and
      denatured beta-casein, one of the most abundant and antigenic caseins, in order
      to develop an indirect competitive ELISA (icELISA) to detect and quantify traces
      of this milk allergen in raw and processed foodstuffs. We developed two specific
      hybridoma clones, 1H3 and 6A12, which recognized beta-casein in its denatured and
      native conformations by indirect ELISA (iELISA). Cross-reaction analysis by
      Western blot and iELISA indicated that these mAbs specifically recognized beta
      casein from bovine and goat milk extracts, while they did not cross-react with
      proteins present in other food matrixes. These highly specific mAbs enabled the
      development of sensitive, reliable and reproducible icELISAs to detect and
      quantify this milk protein allergen in food commodities. The extraction of beta
      casein from foodstuff was efficiently carried out at 60 degrees C for 15 minutes,
      using an extraction buffer containing 1% SDS. The present study establishes a
      valid 1H3 based-icELISA, which allows the detection and quantification -0.29 ppm
      and 0.80 ppm, respectively- of small amounts of beta-casein in raw and processed
      foods. Furthermore, we were able to detect milk contamination in incurred food
      samples with the same sensitivity as a commercial sandwich ELISA thus showing
      that this icELISA constitutes a reliable analytical method for control strategies
      in food industry and allergy prevention.

PMID- 28759642
TI  - Distinctive actions of connexin 46 and connexin 50 in anterior pituitary
      folliculostellate cells.
AB  - Folliculostellate cell gap junctions establish a network for the transmission of
      information within the anterior pituitary. Connexins make up gap junction
      channels. Changes in connexin (Cx) turnover modify gap junction-mediated
      intercellular communication. We have reported that cytokines and hormones
      influence Cx43 turnover and coupling in folliculostellate cells and in the
      folliculostellate cell line TtT/GF. In addition, the expression of different
      connexins alters intercellular communication and connexins may have functions
      besides cell coupling. Here we assessed the expression, turnover and subcellular
      localization of Cx46 and Cx50 in the anterior pituitary and TtT/GF cells. Then,
      we assessed the impact of various natural (lactation, annual reproductive cycle,
      bFGF) and pathological (autoimmune orchitis, diabetes/obesity) conditions
      associated with altered anterior pituitary hormone secretion on Cx46 and Cx50.
      Anterior pituitary Cx46 and Cx50 expression and subcellular distribution were
      cell-dependent. Cx46 was expressed by folliculostellate, TtT/GF and endocrine
      cells. In the cytoplasm, Cx46 was chiefly associated with lysosomes. Variously
      sized Cx46 molecules were recovered exclusively in the TtT/GF cell nuclear
      fraction. In the nucleus, Cx46 co-localized with Nopp-140, a nucleolar factor
      involved in rRNA processing. Neither cytoplasmic nor nuclear Cx46 and Cx43 co
      localized. Cx50 localized to folliculostellate and TtT/GF cells, and to the walls
      of blood capillaries, not to endocrine cells. Cx50 was cytoplasmic and associated
      with the cell membrane, not nuclear. Cx50 did not co-localize with Cx46 but it co
      localized in the cytoplasm and co-immunoprecipitated with Cx43. Cx46 and Cx50
      responses to various physiological and pathological challenges were different,
      often opposite. Cx46 and Cx43 expression and phosphorylation profiles differed in
      the anterior pituitary, whereas Cx50 and Cx43 were similar. The data suggest that
      Cx46 participates to cellular growth and proliferation and that Cx50, together
      with Cx43, contributes to folliculostellate cell coupling.

PMID- 28759643
TI  - In vitro comparison between alpha-tocopheryl acetate and alpha-tocopheryl
      phosphate against bacteria responsible of prosthetic and joint infections.
AB  - Biofilm-related infections represent a recurrent problem in the orthopaedic
      setting. In recent years, great interest was directed towards the identification
      of novel molecules capable to interfere with pathogens adhesion and biofilm
      formation on implant surfaces. In this study, two stable forms of alpha
      tocopherol, the hydrophobic acetate ester and the water-soluble phosphate ester,
      were tested in vitro as coating for titanium prosthesis. Antimicrobial activity
      against microorganisms responsible of prosthetic and joints infections was
      assessed by broth microdilution method. In addition, alpha-tocopherol esters were
      evaluated for both their ability to hamper bacterial adhesion to and biofilm
      formation on sandblasted titanium surfaces. Results showed that only alpha
      tocopheryl phosphate displayed antimicrobial activity against the tested strains.
      Both esters were able to significantly interfere with bacterial adhesion and to
      prevent biofilm formation, especially by Staphylococcus aureus and Staphylococcus
      epidermidis. The activity of alpha-tocopheryl phosphate was greater than that of
      alpha-tocopheryl acetate. Alterations at membrane levels have been reported in
      literature and may be likely responsible for the interference on bacterial
      adhesion and biofilm formation shown by alpha-tocopherol esters. Although further
      studies are needed to better investigate the mechanisms of action and the
      spectrum of activity of alpha-tocopherol esters, these characteristics together
      with the positive effect on wound healing and immune response, make these
      molecules promising candidate for coating in order to prevent implant-associated
      infections.

PMID- 28759644
TI  - The influence of serum uric acid on renal function in patients with calcium or
      uric acid stone: A population-based analysis.
AB  - OBJECTIVES: To determine the influence of serum uric acid (UA) levels on renal
      impairment in patients with UA stone. MATERIALS AND METHODS: We retrospectively
      analyzed 463 patients with calcium oxalate and/or calcium phosphate stones
      (CaOx/CaP), and 139 patients with UA stones. The subjects were divided into the
      serum UA-high (UA >= 7.0 mg/dL) or the UA-low group (UA < 7.0 mg/dL). The control
      group comprised 3082 community-dwelling individuals that were pair-matched
      according to age, sex, body mass index, comorbidities, hemoglobin, serum albumin,
      and serum UA using propensity score matching. We compared renal function between
      controls and patients with UA stone (analysis 1), and between patients with
      CaOx/CaP and with UA stone (analysis 2). Logistic regression analysis was used to
      evaluate the impact of the hyperuricemia on the development of stage 3 and 3B
      chronic kidney disease (CKD) (analysis 3). RESULTS: The renal function was
      significantly associated with serum UA levels in the controls and patients with
      CaOx/CaP and UA stones. In pair-matched subgroups, patients with UA stone had
      significantly lower renal function than the control subjects (analysis 1) and
      patients with CaOx/CaP stones (analysis 2) regardless of hyperuricemia.
      Multivariate logistic regression analysis revealed that patients with UA stone,
      CaOx/CaP, hyperuricemia, presence of cardiovascular disease, higher body mass
      index, older age and lower hemoglobin had significantly higher risk of stage 3
      and 3B CKD (analysis 3). CONCLUSION: Patients with UA stones had significantly
      worse renal function than controls and CaOx/CaP patients regardless of
      hyperuricemia. Urolithiasis (CaOx/CaP and UA stone) and hyperuricemia had an
      association with impaired renal function. Our findings encourage clinicians to
      initiate intensive treatment and education approaches in patients with
      urolithiasis and/or hyperuricemia in order to prevent the progression of renal
      impairment.

PMID- 28759645
TI  - Characteristics of HIV-infected U.S. Army soldiers linked in molecular
      transmission clusters, 2001-2012.
AB  - OBJECTIVE: Recent surveillance data suggests the United States (U.S.) Army HIV
      epidemic is concentrated among men who have sex with men. To identify potential
      targets for HIV prevention strategies, the relationship between demographic and
      clinical factors and membership within transmission clusters based on baseline
      pol sequences of HIV-infected Soldiers from 2001 through 2012 were analyzed.
      METHODS: We conducted a retrospective analysis of baseline partial pol sequences,
      demographic and clinical characteristics available for all Soldiers in active
      service and newly-diagnosed with HIV-1 infection from January 1, 2001 through
      December 31, 2012. HIV-1 subtype designations and transmission clusters were
      identified from phylogenetic analysis of sequences. Univariate and multivariate
      logistic regression models were used to evaluate and adjust for the association
      between characteristics and cluster membership. RESULTS: Among 518 of 995 HIV
      infected Soldiers with available partial pol sequences, 29% were members of a
      transmission cluster. Assignment to a southern U.S. region at diagnosis and year
      of diagnosis were independently associated with cluster membership after
      adjustment for other significant characteristics (p<0.10) of age, race, year of
      diagnosis, region of duty assignment, sexually transmitted infections, last
      negative HIV test, antiretroviral therapy, and transmitted drug resistance.
      Subtyping of the pol fragment indicated HIV-1 subtype B infection predominated
      (94%) among HIV-infected Soldiers. CONCLUSION: These findings identify areas to
      explore as HIV prevention targets in the U.S. Army. An increased frequency of
      current force testing may be justified, especially among Soldiers assigned to
      duty in installations with high local HIV prevalence such as southern U.S.
      states.

PMID- 28759646
TI  - Local cryotherapy improves adjuvant-induced arthritis through down-regulation of
      IL-6 / IL-17 pathway but independently of TNFalpha.
AB  - OBJECTIVES: Local cryotherapy is widely and empirically used in the adjuvant
      setting in rheumatoid arthritis treatment, however its own therapeutic and anti
      inflammatory effects are poorly characterized. We aimed to evaluate the effects
      of local cryotherapy on local and systemic inflammation in Adjuvant-induced
      arthritis, a murine model of rheumatoid arthritis. METHODS: The effects of mild
      hypothermia (30 degrees C for 2 hours) on cytokine protein levels
      (Multiplex/ELISA) were evaluated in vitro in cultured rat adjuvant-induced
      arthritis patellae. In vivo, local cryotherapy was applied twice a day for 14
      days in arthritic rats (ice: n = 10, cold gas: n = 9, non-treated: n = 10). At
      day 24 after the induction of arthritis, cytokine expression levels were measured
      in grinded hind paws (Q-RT-PCR) and in the plasma (Multiplex/ELISA). RESULTS: In
      vitro, punctual mild hypothermia down-regulated IL-6 protein expression. In vivo,
      ice showed a better efficacy profile on the arthritis score and joint swelling
      and was better tolerated, while cold gas induced a biphasic response profile with
      initial, transient arthritis worsening. Local cryotherapy also exerted local and
      systemic anti-inflammatory effects, both at the gene and the protein levels: IL
      6, IL-17A and IL-1beta gene expression levels were significantly down-regulated
      in hind paws. Both techniques decreased plasma IL-17A while ice decreased plasma
      IL-6 protein levels. By contrast, we observed no effect on local/systemic TNF
      alpha pathway. CONCLUSIONS: We demonstrated for the first time that sub
      chronically applied local cryotherapy (ice and cold gas) is an effective and well
      tolerated treatment in adjuvant-induced arthritis. Furthermore, we provided novel
      insights into the cytokine pathways involved in Local cryotherapy's local and
      systemic anti-inflammatory effects, which were mainly IL-6/IL-17A-driven and TNF
      alpha independent in this model.

PMID- 28759647
TI  - Connectivity in gene coexpression networks negatively correlates with rates of
      molecular evolution in flowering plants.
AB  - Gene coexpression networks are a useful tool for summarizing transcriptomic data
      and providing insight into patterns of gene regulation in a variety of species.
      Though there has been considerable interest in studying the evolution of network
      topology across species, less attention has been paid to the relationship between
      network position and patterns of molecular evolution. Here, we generated
      coexpression networks from publicly available expression data for seven flowering
      plant taxa (Arabidopsis thaliana, Glycine max, Oryza sativa, Populus spp.,
      Solanum lycopersicum, Vitis spp., and Zea mays) to investigate the relationship
      between network position and rates of molecular evolution. We found a significant
      negative correlation between network connectivity and rates of molecular
      evolution, with more highly connected (i.e., "hub") genes having significantly
      lower nonsynonymous substitution rates and dN/dS ratios compared to less highly
      connected (i.e., "peripheral") genes across the taxa surveyed. These findings
      suggest that more centrally located hub genes are, on average, subject to higher
      levels of evolutionary constraint than are genes located on the periphery of gene
      coexpression networks. The consistency of this result across disparate taxa
      suggests that it holds for flowering plants in general, as opposed to being a
      species-specific phenomenon.

PMID- 28759648
TI  - Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating
      T helper 17 cell response.
AB  - Anemoside A3 (AA3) is a natural triterpenoid glycoside isolated from the root of
      Pulsatilla chinensis (Bunge) Regel. We previously showed that AA3 exhibits
      cognitive-enhancing and neuroprotective properties. In the present study, we
      demonstrated that AA3 modulates inflammatory responses by regulating
      prostaglandin E receptor 4 signaling. Because prostaglandin E receptor 4 is
      involved in the pathophysiology of experimental autoimmune encephalomyelitis
      (EAE), an animal model of human multiple sclerosis (MS), we assessed the
      beneficial effect of AA3 in EAE mice. AA3 treatment significantly reduced
      clinical severity and inflammatory infiltrates in the spinal cord of EAE mice. In
      vitro studies revealed that AA3 inhibited the T cell response toward the
      encephalitogenic epitope of myelin oligodendrocyte glycoprotein (MOG). AA3
      significantly downregulated the expressions of certain Th1 and Th17 cytokines in
      activated T cells re-stimulated by MOG. Moreover, AA3 inhibited the activation of
      STAT4 and STAT3, which are the transcription factors pivotal for Th1 and Th17
      lineage differentiation, respectively, in activated T cells. Pharmacological
      analysis further suggested that AA3 reduced Th17 cell differentiation and
      expansion. In conclusion, AA3 exerts an immunomodulatory effect in EAE,
      demonstrating its potential as a therapeutic agent for MS in humans.

PMID- 28759650
TI  - MicroRNA expression profiles differ between primary myofiber of lean and obese
      pig breeds.
AB  - MicroRNAs (miRNAs) are non-coding small miRNAs ~22 nucleotides in length and play
      a vital role in muscle development by binding to messenger RNAs (mRNAs). Large
      White (LW, a lean type pig) and Meishan pigs (MS, a Chinese indigenous obese
      breed) have significant postnatal phenotype differences in growth rate, muscle
      mass and meat quality, and these differences are programmed during prenatal
      muscle development. Little research shed light directly on the miRNA
      transcriptome difference in prenatal muscles between these two distinct pig
      breeds. Myofiber phenotypes of LW and MS were measured at developmental stages of
      35, 55 and 90 days post-conception (dpc), which revealed that the myogenesis
      process is more intense in MS than in LW at 35 dpc. To investigate the role of
      miRNAs involved in regulating muscle development at earlier stages of myogenesis
      and decipher the miRNAs transcriptome difference between LW and MS, here, the
      miRNAomes of longissimus dorsi muscle collected at 35 dpc from female LW and MS
      were analyzed by deep sequencing. Overall, 1147 unique miRNAs comprising 434
      known miRNAs, 239 conserved miRNAs and 474 candidate miRNAs were identified.
      Expression analysis of the 10 most abundant miRNAs in every library indicated
      that functional miRNAome may be a small amount and tend to be greater expressed.
      These sets of miRNA may play house keeping roles that were involved in
      myogenesis. A total of 87 miRNAs were significantly differentially expressed
      between LW and MS (reads > 1000, P < 0.05). Gene ontology (GO) and KEGG pathway
      enrichment analysis revealed that the differentially expressed miRNAs (DE miRNAs)
      were associated mainly with muscle contraction, WNT, mTOR, and MAPK signaling
      pathways. Some myogenesis related miRNAs (miR-133, miR-1, miR-206 and miR-148a)
      are highly abundant in MS, while other miRNAs (let-7 family, miR-214, miR-181)
      highly expressed in LW. In addition, the expression patterns of miRNAs (miR-1, 
      133, -206) at three prenatal stages (35, 55 and 90 dpc) were determined using qRT
      PCR. Notably, ssc-miR-133 was significantly more highly expressed in LW pigs
      skeletal muscle at all prenatal stages compared with its expression in LW pigs
      skeletal muscle. Taken together, the main functional miRNAs during muscle
      development are different between lean and obese pig breeds. The present study
      adds new information to existing data on porcine miRNAs and will be helpful to
      investigate the dominant (main functional) muscle-related miRNAs sets in
      different pig breeds.

PMID- 28759649
TI  - The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell
      receptors and proteases.
AB  - Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S)
      proteins binding to cellular receptors, and is followed by proteolytic cleavage
      of receptor-bound S proteins, which prompts S protein-mediated virus-cell
      membrane fusion. Infection therefore requires close proximity of receptors and
      proteases. We considered whether tetraspanins, scaffolding proteins known to
      facilitate CoV infections, hold receptors and proteases together on cell
      membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not
      the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4
      (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease
      (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated
      condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter
      cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated
      by TTSPs, and they trafficked into endosomes to be cleaved much later and less
      efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein
      complexes necessary for early, efficient MERS-CoV entry. To evaluate the
      importance of these complexes in an in vivo CoV infection model, we used
      recombinant Adenovirus 5 (rAd5) vectors to express human DPP4 in mouse lungs,
      thereby sensitizing the animals to MERS-CoV infection. When the rAd5-hDPP4
      vectors co-expressed small RNAs silencing Cd9 or Tmprss2, the animals were
      significantly less susceptible, indicating that CD9 and TMPRSS2 facilitated
      robust in vivo MERS-CoV infection of mouse lungs. Furthermore, the S proteins of
      virulent mouse-adapted MERS-CoVs acquired a CD9-dependent cell entry character,
      suggesting that CD9 is a selective agent in the evolution of CoV virulence.

PMID- 28759652
TI  - Sleep apnoea is common in severe peripheral arterial disease.
AB  - BACKGROUND: Atherosclerotic conditions have been demonstrated to be associated
      with sleep- disordered breathing (SDB). Peripheral arterial disease (PAD)
      represents severe atherosclerosis with a high mortality. In early stages of PAD a
      substantial prevalence of sleep apnoea has already been shown. Here, we sought to
      determine the frequency of undiagnosed sleep apnoea in a homogeneous group of
      advanced PAD patients undergoing percutaneous revascularization. METHODS: 59
      consecutive patients (mean age: 71.1 +/- 9.8 years, 67.8% males) with PAD in
      Fontaine stages IIb-IV that underwent percutaneous transluminal angioplasty at
      our department were enrolled for pre-procedural polygraphy. RESULTS: Patients
      appertained to Fontaine clinical stage IIb, III and IV in 54.2%, 23.8% and 22.%
      of cases, respectively, and were principally intervened for femoropopliteal
      occlusive disease (71.2% of total study population). Polygraphy revealed sleep
      apnoea in 48 out of 59 patients (81.4%), of whom 60.4% offered a primarily
      obstructive-driven genesis. Among those patients with polygraphically confirmed
      sleep apnoea, mean apnoea hypopnoea index (AHI) and mean oxygen desaturation
      index (ODI) averaged 28.2 +/- 19.5/h and 26.7 +/- 18.8/h, respectively. 18
      patients even offered an AHI >=30/h that is indicative of severe sleep apnoea.
      For obstructive-driven apnoeic events, AHI correlated significantly with PAD
      severity stages (p = 0.042). CONCLUSIONS: In our PAD collective, sleep apnoea was
      frequent and obstructive sleep apnoea's severity correlated with PAD severity
      stages. Long-term results regarding the vasoprotective impact of CPAP treatment
      on PAD course remains to be determined.

PMID- 28759653
TI  - High-resolution physicochemical characterization of different intravenous
      immunoglobulin products.
AB  - Intravenous immunoglobulin (IVIg) is a complex mixture drug comprising diverse
      immunoglobulins and non-IgG proteins purified from the plasma of thousands of
      healthy donors. Approved IVIg products on the market differ regarding source of
      plasma, isolation process, and formulation. These products are used widely, and
      often interchangeably, for the treatment of immunodeficiency and autoimmune and
      inflammatory diseases, but their mechanisms of action in different indications
      are not well understood. A primary limitation to understanding the therapeutic
      relevance of specific components within IVIg has been the limited resolution of
      analytics historically implemented to characterize its complex mixture. In this
      study, high-resolution analytics were applied to better understand the
      composition of IVIg and product variations. We characterized three approved IVIg
      products: Gammagard(r), Privigen(r), and Octagam(r). Differences in the
      distribution of molecular weight species, IgG sequence variants, isoforms,
      glycoforms, and the repertoire of previously reported antibody specificities were
      identified. We also compared the effect of aging on these products to identify
      changes in size distribution and posttranslational modifications. This type of
      characterization may provide insights into the specific factors and components of
      IVIg that may influence its activity and ultimately lead to optimization of IVIg
      products for use in autoimmune diseases.

PMID- 28759651
TI  - Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing
      contribute to rapid shifts in dominant quasispecies during acute and early
      infection.
AB  - In order to inform the rational design of HIV-1 preventive and cure interventions
      it is critical to understand the events occurring during acute HIV-1 infection
      (AHI). Using viral deep sequencing on six participants from the early capture
      acute infection RV217 cohort, we have studied HIV-1 evolution in plasma collected
      twice weekly during the first weeks following the advent of viremia. The analysis
      of infections established by multiple transmitted/founder (T/F) viruses revealed
      novel viral profiles that included: a) the low-level persistence of minor T/F
      variants, b) the rapid replacement of the major T/F by a minor T/F, and c) an
      initial expansion of the minor T/F followed by a quick collapse of the same minor
      T/F to low frequency. In most participants, cytotoxic T-lymphocyte (CTL) escape
      was first detected at the end of peak viremia downslope, proceeded at higher
      rates than previously measured in HIV-1 infection, and usually occurred through
      the exploration of multiple mutational pathways within an epitope. The rapid
      emergence of CTL escape variants suggests a strong and early CTL response. Minor
      T/F viral strains can contribute to rapid and varied profiles of HIV-1
      quasispecies evolution during AHI. Overall, our results demonstrate that early,
      deep, and frequent sampling is needed to investigate viral/host interaction
      during AHI, which could help identify prerequisites for prevention and cure of
      HIV-1 infection.

PMID- 28759655
TI  - Synthesis and thermodynamic properties of arsenate and sulfate-arsenate
      ettringite structure phases.
AB  - Arsenic is a toxic and carcinogenic contaminant of potential concern. Ettringite
      [Ca6Al2(SO4)3(OH)12.26H2O] has the ability to incorporate oxyanions as a solid
      solution with SO42-, which could lower the soluble oxyanion concentrations.
      Therefore, ettringite containing SO42- and AsO43- has been synthesized. Results
      indicated that AsO43- could substitute for SO42- inside the channels of
      ettringite in the form of HAsO42-, and a linear correlation existed between
      Xinitial solution and Xsolid. The thermodynamic characterization of the solid
      samples was investigated by means of Visual MINTEQ, a freeware chemical
      equilibrium model, and the solubility product logK of -48.4 +/- 0.4 was
      calculated for HAsO4-ettringite at 25 degrees C. The Lippmann phase diagram and
      XHAsO4-XHAsO4,aq plot showed that the solid solution series containing arsenate
      has HAsO4-poor aqueous solutions in equilibrium. These findings can be helpful to
      arsenate solidification and arsenate leaching modeling projects.

PMID- 28759654
TI  - Surgical resection of metachronous hepatic metastases from gastric cancer
      improves long-term survival: A population-based study.
AB  - INTRODUCTION: Hepatic metastases are diagnosed synchronously in 3-14% of patients
      with gastric cancer, and metachronously in up to 37% of patients following
      ''curative" gastrectomy. Most patients who have gastric cancer and hepatic
      metastasis are traditionally treated with palliative chemotherapy. The impact of
      liver resection is still controversial. We attempted to assess whether liver
      resection can improve survival in cases of metachronous hepatic metastases from
      gastric cancer through a nationwide database. MATERIALS AND METHODS: We conducted
      a nationwide cohort study using a claims dataset from Taiwan's National Health
      Insurance Research Database (NHIRD). We identified all patients with gastric
      cancer (diagnostic code ICD-9: 151.x) from the Registry for Catastrophic Illness
      Patient Database (RCIPD) of the NHIRD who received gastrectomy and as well as
      those with metachronous (>=180 days after gastrectomy) liver metastases (ICD-9
      code: 197.7) between 1996/01/01 and 2012/12/31. Patients with other malignancies,
      with metastasis in the initial admission for gastrectomy and with other
      metastases were excluded. They were divided into two groups, liver resection
      group and non-resection group. All patients were followed till 2013/12/31 or
      withdrawn from the database because of death. RESULTS: 653 patients who
      fullfilled the inclusion criteria were included in the research. They were
      divided into liver resection group (34 patients) and non-resection group (619
      patients). There were no differences between the two groups in gender, Charlson
      Comorbidity index and major coexisting disease. Kaplan-Meier analysis demostrated
      the liver resection group had significantly better overall survival than the non
      resection group. (1YOS: 73.5% vs. 19.7%, 3YOS: 36.9% vs. 6.6%, 5YOS: 24.5.3% vs.
      4.4%, p <0.001). After COX analysis, the liver resection group showed statistical
      significance for improved patient survival (HR = 0.377, 95%CI: 0.255-0.556.
      p<0.001). CONCLUSION: Liver resection in patients presenting with metachronous
      hepatic metastases as the sole metastases after curative resection of gastric
      cancer is associated with a significant survival improvement and should be
      considered a treatment option for such patients.

PMID- 28759664
TI  - The Benefit of Early Preventive Dental Care for Children.

PMID- 28759656
TI  - The effect of disease and respiration on airway shape in patients with moderate
      persistent asthma.
AB  - Computational models of gas transport and aerosol deposition frequently utilize
      idealized models of bronchial tree structure, where airways are considered a
      network of bifurcating cylinders. However, changes in the shape of the lung
      during respiration affect the geometry of the airways, especially in disease
      conditions. In this study, the internal airway geometry was examined,
      concentrating on comparisons between mean lung volume (MLV) and total lung
      capacity (TLC). A set of High Resolution CT images were acquired during breath
      hold on a group of moderate persistent asthmatics at MLV and TLC after challenge
      with a broncho-constrictor (methacholine) and the airway trees were segmented and
      measured. The airway hydraulic diameter (Dh) was calculated through the use of
      average lumen area (Ai) and average internal perimeter (Pi) at both lung volumes
      and was found to be systematically higher at TLC by 13.5+/-9% on average, with
      the lower lobes displaying higher percent change in comparison to the lower
      lobes. The average internal diameter (Din) was evaluated to be 12.4+/-6.8% (MLV)
      and 10.8+/-6.3% (TLC) lower than the Dh, for all the examined bronchi, a result
      displaying statistical significance. Finally, the airway distensibility per
      bronchial segment and per generation was calculated to have an average value of
      0.45+/-0.28, exhibiting high variability both between and within lung regions and
      generations. Mixed constriction/dilation patterns were recorded between the lung
      volumes, where a number of airways either failed to dilate or even constricted
      when observed at TLC. We conclude that the Dh is higher than Din, a fact that may
      have considerable effects on bronchial resistance or airway loss at proximal
      regions. Differences in caliber changes between lung regions are indicative of
      asthma-expression variability in the lung. However, airway distensibility at
      generation 3 seems to predict distensibility more distally.

PMID- 28759657
TI  - HIV-1 infection depletes human CD34+CD38- hematopoietic progenitor cells via pDC
      dependent mechanisms.
AB  - Chronic human immunodeficiency virus-1 (HIV-1) infection in patients leads to
      multi-lineage hematopoietic abnormalities or pancytopenia. The deficiency in
      hematopoietic progenitor cells (HPCs) induced by HIV-1 infection has been
      proposed, but the relevant mechanisms are poorly understood. We report here that
      both human CD34+CD38- early and CD34+CD38+ intermediate HPCs were maintained in
      the bone marrow (BM) of humanized mice. Chronic HIV-1 infection preferentially
      depleted CD34+CD38- early HPCs in the BM and reduced their proliferation
      potential in vivo in both HIV-1-infected patients and humanized mice, while
      CD34+CD38+ intermediate HSCs were relatively unaffected. Strikingly, depletion of
      plasmacytoid dendritic cells (pDCs) prevented human CD34+CD38- early HPCs from
      HIV-1 infection-induced depletion and functional impairment and restored the gene
      expression profile of purified CD34+ HPCs in humanized mice. These findings
      suggest that pDCs contribute to the early hematopoietic suppression induced by
      chronic HIV-1 infection and provide a novel therapeutic target for the
      hematopoiesis suppression in HIV-1 patients.

PMID- 28759665
TI  - Association Between Sponsorship and Findings of Medical Home Evaluations.

PMID- 28759663
TI  - Association Between Birth in a High Stroke Mortality State, Race, and Risk of
      Dementia.
AB  - Importance: Birth in a group of predominantly southern US states is robustly
      linked to increased stroke risk. Given the role of cerebrovascular disease in
      dementia risk, geographic patterning may also occur for dementia incidence.
      Objective: To determine whether birth in 9 high stroke mortality states (HSMSs)
      is associated with dementia in a diverse cohort of individuals living in Northern
      California. Design, Setting, and Participants: An observational cohort study
      included 7423 members of Kaiser Permanente Northern California (KPNC), an
      integrated health care delivery system, with health survey and clinical
      examination data available. Data were collected between 1964 and 1973 when the
      individuals were middle-aged and 1996 and 2015 when participants were in later
      life. Exposures: Self-reported state of birth in an HSMS (top quintile of states
      for stroke mortality). Main Outcomes and Measures: Dementia diagnoses obtained
      from electronic health records from January 1, 1996, to October 15, 2015. Place
      of birth, race, educational level, and midlife vascular risk factors data were
      collected between 1964 and 1973. Results: Of the 7423 persons included in the
      analysis, 4049 (54.5%) were women; 1354 (18.2%) were black. The mean (SD) age of
      study participants at their first visit between 1963 and 1974 was 42.94 (1.73)
      years and mean (SD) age at the beginning of follow-up for dementia in 1996 was
      71.14 (2.72) years. Dementia was diagnosed in 2254 (30.4%) of the participants
      and was more common among those born in an HSMS than those born outside of one
      (455 [39.0%] vs 1799 [28.8%]). Birth in an HSMS was 9.6 times more common for
      black participants (795 [58.7%]) than nonblack participants (371 [6.1%]).
      Overall, birth in an HSMS was associated with a 28% higher risk of dementia
      (adjusted hazard ratio [aHR], 1.28; 95% CI, 1.13-1.46) adjusted for age, sex, and
      race. Compared with nonblack persons born outside of an HSMS, black individuals
      born in an HSMS had the highest dementia risk (aHR, 1.67; 95% CI, 1.48-1.88),
      followed by black individuals not born in an HSMS (aHR, 1.48; 95% CI, 1.28-1.72),
      and nonblack persons born in an HSMS had a 46% increased risk (aHR, 1.46; 95% CI,
      1.23-1.74). Cumulative 20-year dementia risks at age 65 years were 30.13% (95%
      CI, 26.87%-32.93%) and 21.80% (95% CI, 20.51%-22.91%) for individuals born in and
      outside an HSMS, respectively. Conclusions and Relevance: To our knowledge, this
      is the first study to date of place of birth and incident dementia and shows
      increased risk for individuals born in an HSMS, even though all participants
      subsequently resided in California. Birth in an HSMS was common among black
      participants. Place of birth has enduring consequences for dementia risk and may
      be a major contributor to racial disparities in dementia.

PMID- 28759668
TI  - The Benefit of Early Preventive Dental Care for Children.

PMID- 28759666
TI  - Association of Genetic Predisposition With Solitary Schwannoma or Meningioma in
      Children and Young Adults.
AB  - Importance: Meningiomas and schwannomas are usually sporadic, isolated tumors
      occurring in adults older than 60 years and are rare in children and young
      adults. Multiple schwannomas and/or meningiomas are more frequently associated
      with a tumor suppressor syndrome and, accordingly, trigger genetic testing,
      whereas solitary tumors do not. Nevertheless, apparently sporadic tumors in young
      patients may herald a genetic syndrome. Objective: To determine the frequency of
      the known heritable meningioma- or schwannoma-predisposing mutations in children
      and young adults presenting with a solitary meningioma or schwannoma. Design,
      Setting, and Participants: Using the database of the Manchester Centre for
      Genomic Medicine, this cohort study analyzed lymphocyte DNA from young
      individuals prospectively referred to the clinic for genetic testing between
      January 1, 1990, and December 31, 2016, on presentation with a single meningioma
      (n = 42) or schwannoma (n = 135) before age 25 years. Sequencing data were also
      examined from an additional 39 patients with neurofibromatosis type 2 who were
      retrospectively identified as having a solitary tumor before age 25 years.
      Patients with schwannoma were screened for NF2, SMARCB1, and LZTR1 gene
      mutations, while patients with meningioma were screened for NF2, SMARCB1,
      SMARCE1, and SUFU. Main Outcomes and Measures: The type of underlying genetic
      mutation, or lack of a predisposing mutation, was associated with the presenting
      tumor type and subsequent development of additional tumors or other features of
      known schwannoma- and meningioma-predisposing syndromes. Results: In 2 cohorts of
      patients who presented with an isolated meningioma (n = 42; median [range] age,
      11 [1-24] years; 22 female) or schwannoma (n = 135; median [range] age, 18 [0.2
      24] years; 60 female) before age 25 years, 16 of 42 patients (38%) had a
      predisposing mutation to meningioma and 27 of 135 patients (20%) to schwannoma,
      respectively. In the solitary meningioma cohort, 34 of 63 patients (54%) had a
      constitutional mutation in a known meningioma predisposition gene. Twenty-five of
      63 patients (40%) had a constitutional NF2 mutation, and 9 (14%) had a
      constitutional SMARCE1 mutation. In the cohort of those who developed a solitary
      schwannoma before age 25 years, 44 of 153 patients (29%) had an identifiable
      genetic predisposition. Twenty-four patients (55%) with a spinal schwannoma had a
      constitutional mutation, while only 20 (18%) with a cranial schwannoma had a
      constitutional predisposition (P < .001). Of 109 cranial schwannomas, 106 (97.2%)
      were vestibular. Four of 106 people (3.8%) with a cranial schwannoma had an LZTR1
      mutation (3 were vestibular schwannomas and 1 was a nonvestibular schwannoma),
      and 9 (8.5%) had an NF2 mutation. Conclusions and Relevance: A significant
      proportion of young people with an apparently sporadic solitary meningioma or
      schwannoma had a causative predisposition mutation. This finding has important
      clinical implications because of the risk of additional tumors and the
      possibility of familial disease. Young patients presenting with a solitary
      meningioma or schwannoma should be referred for genetic testing.

PMID- 28759669
TI  - The Benefit of Early Preventive Dental Care for Children.

PMID- 28759670
TI  - Sharing the Process of Diagnostic Decision Making.

PMID- 28759667
TI  - Early-Life Epilepsies and the Emerging Role of Genetic Testing.
AB  - Importance: Early-life epilepsies are often a consequence of numerous
      neurodevelopmental disorders, most of which are proving to have genetic origins.
      The role of genetic testing in the initial evaluation of these epilepsies is not
      established. Objective: To provide a contemporary account of the patterns of use
      and diagnostic yield of genetic testing for early-life epilepsies. Design,
      Setting, and Participants: In this prospective cohort, children with newly
      diagnosed epilepsy with an onset at less than 3 years of age were recruited from
      March 1, 2012, to April 30, 2015, from 17 US pediatric hospitals and followed up
      for 1 year. Of 795 families approached, 775 agreed to participate. Clinical
      diagnosis of the etiology of epilepsy were characterized based on information
      available before genetic testing was performed. Added contributions of
      cytogenetic and gene sequencing investigations were determined. Exposures:
      Genetic diagnostic testing. Main Outcomes and Measures: Laboratory-confirmed
      pathogenic variant. Results: Of the 775 patients in the study (367 girls and 408
      boys; median age of onset, 7.5 months [interquartile range, 4.2-16.5 months]), 95
      (12.3%) had acquired brain injuries. Of the remaining 680 patients, 327 (48.1%)
      underwent various forms of genetic testing, which identified pathogenic variants
      in 132 of 327 children (40.4%; 95% CI, 37%-44%): 26 of 59 (44.1%) with
      karyotyping, 32 of 188 (17.0%) with microarrays, 31 of 114 (27.2%) with epilepsy
      panels, 11 of 33 (33.3%) with whole exomes, 4 of 20 (20.0%) with mitochondrial
      panels, and 28 of 94 (29.8%) with other tests. Forty-four variants were
      identified before initial epilepsy presentation. Apart from dysmorphic syndromes,
      pathogenic yields were highest for children with tuberous sclerosis complex (9 of
      11 [81.8%]), metabolic diseases (11 of 14 [78.6%]), and brain malformations (20
      of 61 [32.8%]). A total of 180 of 446 children (40.4%), whose etiology would have
      remained unknown without genetic testing, underwent some testing. Pathogenic
      variants were identified in 48 of 180 children (26.7%; 95% CI, 18%-34%).
      Diagnostic yields were greater than 15% regardless of delay, spasms, and young
      age. Yields were greater for epilepsy panels (28 of 96 [29.2%]; P < .001) and
      whole exomes (5 of 18 [27.8%]; P = .02) than for chromosomal microarray (8 of 101
      [7.9%]). Conclusions and Relevance: Genetic investigations, particularly broad
      sequencing methods, have high diagnostic yields in newly diagnosed early-life
      epilepsies regardless of key clinical features. Thorough genetic investigation
      emphasizing sequencing tests should be incorporated into the initial evaluation
      of newly presenting early-life epilepsies and not just reserved for those with
      severe presentations and poor outcomes.

PMID- 28759671
TI  - Internet Searches for Suicide Following the Release of 13 Reasons Why.

PMID- 28759672
TI  - High-Throughput Sequencing as First-Tier Diagnostics in Congenital and Early
      Onset Disorders.

PMID- 28759673
TI  - The Benefit of Early Preventive Dental Care for Children-Reply.

PMID- 28759674
TI  - A Call for Social Responsibility and Suicide Risk Screening, Prevention, and
      Early Intervention Following the Release of the Netflix Series 13 Reasons Why.

PMID- 28759675
TI  - High-speed spatial frequency domain imaging with temporally modulated light.
AB  - Spatial frequency domain imaging (SFDI) is a wide-field diffuse optical technique
      used to obtain optical properties and chromophore concentrations in highly
      scattering media, such as biological tissue. Here, we present a method for
      rapidly acquiring multispectral SFDI data by modulating each illumination
      wavelength at a different temporal frequency. In the remitted signal, each
      wavelength is temporally demodulated and processed using conventional SFDI
      techniques. We demonstrate a proof-of-concept system capable of acquiring wide
      field maps (2048*1536  pixels, 8.5*6.4  cm) of optical properties at three
      wavelengths in under 2.5 s. Data acquired by this method show a good agreement
      with a commercial SFDI imaging system (with an average error of 13% in absorption
      and 8% in scattering). Additionally, we show that this strategy is insensitive to
      ambient lighting conditions, making it more practical for clinical translation.
      In the future, this technique could be expanded to tens or hundreds of
      wavelengths without increasing acquisition time.

PMID- 28759677
TI  - Modulation of ultrasound-switchable fluorescence for improving signal-to-noise
      ratio.
AB  - Simultaneously achieving high signal-to-noise ratio (SNR) (or sensitivity) and
      high resolution is desired in biomedical imaging. However, conventional imaging
      modality has a tradeoff between SNR (or sensitivity) and resolution. We developed
      a method to simultaneously achieve high SNR (or sensitivity) and high resolution
      for fluorescence imaging in deep tissue. We first introduce a recently developed
      deep-tissue high-resolution imaging technique termed as ultrasound-switchable
      fluorescence (USF). An approach of modulating ultrasound exposure time is adopted
      to increase the detectability of the USF signal. The control parameters of
      modulation of ultrasound-such as (1) frequency, (2) duty cycle, and (3) exposure
      duration-are varied to study their influence on the USF signal and SNR. We
      conclude that high SNR can be achieved by modulating ultrasound exposure without
      sacrificing the spatial resolution. This is important for future fluorescence
      molecular imaging of cancer in deep tissue.

PMID- 28759676
TI  - Dynamic measurement of the optical properties of bovine enamel demineralization
      models using four-dimensional optical coherence tomography.
AB  - Dental enamel mineral loss is multifactorial and is consequently explored using a
      variety of in vitro models. Important factors include the presence of acidic pH
      and its specific ionic composition, which can both influence lesion
      characteristics. Optical coherence tomography (OCT) has been demonstrated as a
      promising tool for studying dental enamel demineralization. However, OCT-based
      characterization and comparison of demineralization model dynamics are
      challenging without a consistent experimental environment. Therefore, an
      automated four-dimensional OCT system was integrated with a multispecimen flow
      cell to measure and compare the optical properties of subsurface enamel
      demineralization in different models. This configuration was entirely automated,
      thus mitigating any need to disturb the specimens and ensuring spatial
      registration of OCT image volumes at multiple time points. Twelve bovine enamel
      disks were divided equally among three model groups. The model demineralization
      solutions were citric acid (pH 3.8), acetic acid (pH 4.0), and acetic acid with
      added calcium and phosphate (pH 4.4). Bovine specimens were exposed to the
      solution continuously for 48 h. Three-dimensional OCT data were obtained
      automatically from each specimen at a minimum of 1-h intervals from the same
      location within each specimen. Lesion dynamics were measured in terms of the
      depth below the surface to which the lesion extended and the attenuation
      coefficient. The net loss of surface enamel was also measured for comparison.
      Similarities between the dynamics of each model were observed, although there
      were also distinct characteristic differences. Notably, the attenuation
      coefficients showed a systematic offset and temporal shift with respect to the
      different models. Furthermore, the lesion depth curves displayed a discontinuous
      increase several hours after the initial acid challenge. This work demonstrated
      the capability of OCT to distinguish between different enamel demineralization
      models by making dynamic quantitative measurements of lesion properties. This has
      important implications for future applications in clinical dentistry.

PMID- 28759678
TI  - Diagnostic Stewardship-Leveraging the Laboratory to Improve Antimicrobial Use.

PMID- 28759679
TI  - The Benefit of Early Preventive Dental Care for Children.

PMID- 28759680
TI  - The Importance of Independent Evaluation.

PMID- 28759682
TI  - Contemporary Legal Updates to the Definition of Brain Death in Nevada.

PMID- 28759681
TI  - Progress Toward Universal Health Coverage: A Comparative Analysis in 5 South
      Asian Countries.
AB  - Importance: Achieving universal health coverage is one of the key targets in the
      newly adopted Sustainable Development Goals of the United Nations. Objective: To
      investigate progress toward universal health coverage in 5 South Asian countries
      and assess inequalities in health services and financial risk protection
      indicators. Design and Settings: In a population-based study, nationally
      representative household (335 373 households) survey data from Afghanistan (2014
      and 2015), Bangladesh (2010 and 2014), India (2012 and 2014), Nepal (2014 and
      2015), and Pakistan (2014) were used to calculate relative indices of health
      coverage, financial risk protection, and inequality in coverage among wealth
      quintiles. The study was conducted from June 2012 to February 2016. Main Outcomes
      and Measures: Three dimensions of universal health coverage were assessed: access
      to basic services, financial risk protection, and equity. Composite and indicator
      specific coverage rates, stratified by wealth quintiles, were then estimated.
      Slope and relative index of inequality were used to assess inequalities in
      service and financial indicators. Results: Access to basic care varied
      substantially across all South Asian countries, with mean rates of overall
      prevention coverage and treatment coverage of 53.0% (95% CI, 42.2%-63.6%) and
      51.2% (95% CI, 45.2%-57.1%) in Afghanistan, 76.5% (95% CI, 61.0%-89.0%) and 44.8%
      (95% CI, 37.1%-52.5%) in Bangladesh, 74.2% (95% CI, 57.0%-88.1%) and 83.5% (95%
      CI, 54.4%-99.1%) in India, 76.8% (95% CI, 66.5%-85.7%) and 57.8% (95% CI, 50.1%
      65.4%) in Nepal, and 69.8% (95% CI, 58.3%-80.2%) and 50.4% (95% CI, 37.1%-63.6%)
      in Pakistan. Financial risk protection was generally low, with 15.3% (95% CI,
      14.7%-16.0%) of respondents in Afghanistan, 15.8% (95% CI, 14.9%-16.8%) in
      Bangladesh, 17.9% (95% CI, 17.7%-18.2%) in India, 11.8% (95% CI, 11.8%-11.9%) in
      Nepal, and 4.4% (95% CI, 4.0%-4.9%) in Pakistan reporting incurred catastrophic
      payments due to health care costs. Access to at least 4 antenatal care visits,
      institutional delivery, and presence of skilled attendant during delivery were at
      least 3 times higher among the wealthiest mothers in Afghanistan, Bangladesh,
      Nepal, and Pakistan compared with the rates among poor mothers. Access to
      institutional delivery was 60 to 65 percentage points higher among wealthy than
      poor mothers in Afghanistan, Bangladesh, Nepal, and Pakistan compared with 21
      percentage points higher in India. Coverage was least equitable among the
      countries for adequate sanitation, institutional delivery, and the presence of
      skilled birth attendants. Conclusions and Relevance: Health coverage and
      financial risk protection was low, and inequality in access to health care
      remains a serious issue for these South Asian countries. Greater progress is
      needed to improve treatment and preventive services and financial security.

PMID- 28759683
TI  - Outcomes in South Asia Matter for the World.

PMID- 28759684
TI  - Impact of Birth Place and Geographic Location on Risk Disparities in
      Cerebrovascular Disease: Implications for Future Research.

PMID- 28759685
TI  - Association Between Extending CareFirst's Medical Home Program to Medicare
      Patients and Quality of Care, Utilization, and Spending.
AB  - Importance: CareFirst, the largest commercial insurer in the mid-Atlantic Region
      of the United States, runs a medical home program focusing on financial
      incentives for primary care practices and care coordination for high-risk
      patients. From 2013 to 2015, CareFirst extended the program to Medicare fee-for
      service (FFS) beneficiaries in participating practices. If the model extension
      improved quality while reducing spending, the Centers for Medicare and Medicaid
      Services could expand the program to Medicare beneficiaries broadly. Objective:
      To test whether extending CareFirst's program to Medicare FFS patients improves
      care processes and reduces hospitalizations, emergency department visits, and
      spending. Design, Setting, and Participants: This difference-in-differences
      analysis compared outcomes for roughly 35 000 Medicare FFS patients attributed to
      52 intervention practices (grouped by CareFirst into 14 "medical panels") to
      outcomes for 69 000 Medicare patients attributed to 42 matched comparison panels
      during a 1-year baseline period and 2.5-year intervention at Maryland primary
      care practices. Main Outcomes and Measures: Hospitalizations (all-cause and
      ambulatory-care sensitive), emergency department visits, Medicare Part A and B
      spending, and 3 quality-of-care process measures: ambulatory care within 14 days
      of a hospital stay, cholesterol testing for those with ischemic vascular disease,
      and a composite measure for those with diabetes. Interventions: CareFirst hired
      nurses who worked with patients' usual primary care practitioners to coordinate
      care for 3656 high-risk Medicare patients. CareFirst paid panels rewards for
      meeting cost and quality targets for their Medicare patients and advised panels
      on how to meet these targets based on analyses of claims data. Results: On
      average, each of the 14 intervention panels had 9.3 primary care practitioners
      and was attributed 2202 Medicare FFS patients in the baseline period. The panels'
      attributed Medicare patients were, on average, 73.8 years old, 59.2% female, and
      85.1% white. The extension of CareFirst's program to Medicare patients was not
      statistically associated with improvements in any outcomes, either for the full
      Medicare population or for a high-risk subgroup in which impacts were expected to
      be largest. For the full population, the difference-in-differences estimates were
      1.4 hospitalizations per 1000 patients per quarter (P = .54; 90% CI, -2.1 to
      5.0), -2.5 outpatient ED visits per 1000 patients per quarter (P = .26; 90% CI, 
      6.2 to 1.1), and -$1 per patient per month in Medicare Part A and B spending (P =
      .98; 90% CI, -$40 to $39). For hospitalizations and Medicare spending, the 90%
      CIs did not span CareFirst's expected impacts. Hospitalizations for the
      intervention group declined by 10% from baseline year to the final 18 months of
      the intervention, but this was matched by similar declines in the comparison
      group. Conclusion and Relevance: The extension of CareFirst's program to Medicare
      did not measurably improve quality-of-care processes or reduce service use or
      spending for Medicare patients. Further program refinement and testing would be
      needed to support scaling the program more broadly to Medicare patients.

PMID- 28759687
TI  - Our Glocal Community.

PMID- 28759688
TI  - The Nursing Professional Development Practitioner and RN Retention.
AB  - Nursing professional development practitioners spend time and energy on the
      education and career development of RNs, but are there strategies that can be
      used to support the retention of experienced staff? This article examines the use
      of a professional development assessment tool as a discussion for career pathway
      support and RN retention. J Contin Educ Nurs. 2017;48(8):340-342.

PMID- 28759686
TI  - Diagnostic Impact and Cost-effectiveness of Whole-Exome Sequencing for Ambulant
      Children With Suspected Monogenic Conditions.
AB  - Importance: Optimal use of whole-exome sequencing (WES) in the pediatric setting
      requires an understanding of who should be considered for testing and when it
      should be performed to maximize clinical utility and cost-effectiveness.
      Objectives: To investigate the impact of WES in sequencing-naive children
      suspected of having a monogenic disorder and evaluate its cost-effectiveness if
      WES had been available at different time points in their diagnostic trajectory.
      Design, Setting, and Participants: This prospective study was part of the
      Melbourne Genomics Health Alliance demonstration project. At the ambulatory
      outpatient clinics of the Victorian Clinical Genetics Services at the Royal
      Children's Hospital, Melbourne, Australia, children older than 2 years suspected
      of having a monogenic disorder were prospectively recruited from May 1 through
      November 30, 2015, by clinical geneticists after referral from general and
      subspecialist pediatricians. All children had nondiagnostic microarrays and no
      prior single-gene or panel sequencing. Exposures: All children underwent
      singleton WES with targeted phenotype-driven analysis. Main Outcomes and
      Measures: The study examined the clinical utility of a molecular diagnosis and
      the cost-effectiveness of alternative diagnostic trajectories, depending on
      timing of WES. Results: Of 61 children originally assessed, 44 (21 [48%] male and
      23 [52%] female) aged 2 to 18 years (mean age at initial presentation, 28 months;
      range, 0-121 months) were recruited, and a diagnosis was achieved in 23 (52%) by
      singleton WES. The diagnoses were unexpected in 8 of 23 (35%), and clinical
      management was altered in 6 of 23 (26%). The mean duration of the diagnostic
      odyssey was 6 years, with each child having a mean of 19 tests and 4 clinical
      genetics and 4 nongenetics specialist consultations, and 26 (59%) underwent a
      procedure while under general anesthetic for diagnostic purposes. Economic
      analyses of the diagnostic trajectory identified that WES performed at initial
      tertiary presentation resulted in an incremental cost savings of A$9020 (US$6838)
      per additional diagnosis (95% CI, A$4304-A$15 404 [US$3263-US$11 678]) compared
      with the standard diagnostic pathway. Even if WES were performed at the first
      genetics appointment, there would be an incremental cost savings of A$5461
      (US$4140) (95% CI, A$1433-A$10 557 [US$1086- US$8004]) per additional diagnosis
      compared with the standard diagnostic pathway. Conclusions and Relevance:
      Singleton WES in children with suspected monogenic conditions has high diagnostic
      yield, and cost-effectiveness is maximized by early application in the diagnostic
      pathway. Pediatricians should consider early referral of children with
      undiagnosed syndromes to clinical geneticists.

PMID- 28759689
TI  - Fostering Personal Power During Change.
AB  - Managing change is a regular part of the role of professional development
      leaders. This overview of a model for change management includes the review of a
      tool leaders can use with their teams for understanding, discussing, and
      reflecting on change. Kotter's change model emphasizes the importance of personal
      empowerment within the process. Effective change agents recognize the value of
      diverse teams, different ways of thinking, and the transformative nature of
      change. J Contin Educ Nurs. 2017;48(8):343-344.

PMID- 28759690
TI  - Use of the 1-Minute Preceptor Model as a Tool in Working With Nurses.
AB  - New graduates, newly hired nurses, and nurses transitioning to new specialties
      need thoughtful and thorough oversight during this process both to ensure
      acquisition of the required skill set and to become an integral part of the new
      area. Well-prepared preceptors who facilitate this education can decrease
      turnover and help to build a healthy work environment. J Contin Educ Nurs.
      2017;48(8):345-346.

PMID- 28759691
TI  - Educational Intervention for Clinical Judgment Skills.
AB  - BACKGROUND: Because nurses need to handle a broad range of issues related to
      patients' health status, it is necessary to make reliable and sound clinical
      judgments for professional accountability and the patients' safety. METHOD: A
      quasi-experimental pre- and posttest design with a control group was used to
      study the effectiveness of an educational intervention on the clinical judgment
      skills of 80 RNs from two district hospitals. The change in clinical judgment
      skills during a 6-week period was evaluated using a complex case-based scenario
      after the completion of the educational intervention. RESULTS: The mean scores of
      clinical judgment skills of the experimental group had significantly improved
      from 24.15 +/- 6.92 to 47.38 +/- 7.20. (p < .001). However, only a slight change
      was seen in mean scores for the control group (23.80 +/- 5.77 to 26.50 +/- 6.53).
      CONCLUSION: The educational intervention was effective postintervention.
      Continuing nursing education using a traditional and case-based method is
      recommended to improve clinical judgment skills in clinical settings. J Contin
      Educ Nurs. 2017;48(8):347-352.

PMID- 28759692
TI  - A Nurse-Led Innovation in Education: Implementing a Collaborative
      Multidisciplinary Grand Rounds.
AB  - Multidisciplinary grand rounds provides an opportunity to promote excellence in
      patient care through scholarly presentations and interdisciplinary collaboration
      with an innovative approach. In addition, multidisciplinary grand rounds serves
      to recognize expertise of staff, mentor and support professional development, and
      provide a collaborative environment across all clinical disciplines and support
      services. This article describes a process model developed by nurse educators for
      implementing a multidisciplinary grand rounds program. The components of the
      process model include topic submissions, coaching presenters, presentations,
      evaluations, and spreading the work. This model can be easily implemented at any
      organization. J Contin Educ Nurs. 2017;48(8):353-357.

PMID- 28759693
TI  - Development and Implementation of an Educational Module to Increase Nurses'
      Comfort With Spiritual Care in an Inpatient Setting.
AB  - Increasing focus is being placed on providing spiritual care for patients as a
      component of holistic nursing care. Studies indicate that patients whose
      spiritual needs are met report higher quality of and satisfaction with their
      care. However, nurses are not including spiritual assessment and care into their
      practice. One barrier cited by nurses is that they lack educational preparation.
      A 2-hour, face-to-face educational module about the provision of spiritual care
      was implemented for inpatient nursing staff at a large academic medical center.
      Program evaluations of the module suggested an increase in the comfort of nurses
      providing spiritual care. This article describes the development and
      implementation of this educational program, with preliminary results. J Contin
      Educ Nurs. 2017;48(8):358-364.

PMID- 28759694
TI  - Doctorate of Nursing Practice Students' Impressions of Uses for Visual Thinking
      Strategies.
AB  - Visual Thinking Strategies (VTS) is a structured art-viewing technique designed
      to teach critical thinking and aesthetic appreciation. Literature on how VTS
      might be used in nursing is just emerging. This qualitative descriptive study
      examined written responses to how 14 doctorate of nursing practice students
      thought they might use VTS in their practice after engaging in a classroom
      session. Three themes emerged for how nurses might use VTS: Facilitating
      Interpersonal Relationships, Changing Thinking in Practice, and As a Teaching
      Tool. This study contributes to the growing body of literature that suggests that
      art and VTS and can be used in nursing with practitioners of all levels to
      promote conversations that involve listening intently and considering other
      possibilities. J Contin Educ Nurs. 2017;48(8):365-368.

PMID- 28759695
TI  - Designing Integrated Courses in an RN-to-BSN Program.
AB  - Three faculty members and an instructional designer collaborated to develop and
      implement first-term courses in a newly revised RN-to-bachelor of science in
      nursing curriculum. The ADDIE model served as the organizing framework for course
      development. Student assessment was approached in a novel manner, using
      integrated assignments that spanned each course. Students were able to
      demonstrate that objectives for all three courses were met, while synthesizing
      and applying their newly gained knowledge and skills. J Contin Educ Nurs.
      2017;48(8):369-372.

PMID- 28759696
TI  - Structured Coaching Programs to Develop Staff.
AB  - Health care environments are complex and chaotic, therein challenging patients
      and professionals to attain satisfaction, well-being, and exceptional outcomes.
      These chaotic environments increase the stress and burnout of professionals and
      reduce the likelihood of optimizing success in many dimensions. Coaching is
      evolving as a professional skill that may influence the optimization of the
      health care environment. This article reflects on three coaching programs: Gallup
      Strengths-Based Coaching, Dartmouth Microsystem Coaching, and Health and Wellness
      Nurse Coaching. Each approach is presented, processes and outcomes are
      considered, and implications for educators are offered. Continuing education
      departments may recognize various coaching approaches as opportunities to support
      staff professionals achieve not only the triple aim, but also the quadruple aim.
      J Contin Educ Nurs. 2017;48(8):373-378.

PMID- 28759697
TI  - Genetics Education in Nurse Residency Programs: A Natural Fit.
AB  - Scientific advances are shedding light on the genetic underpinning of common
      diseases. With such insight, the entire health care team is faced with the need
      to address patient questions regarding genetic risk, testing, and the
      psychosocial aspects of genetics information. Nurses are in a prime position to
      help with patient education about genetic conditions, yet they often lack
      adequate genetics education within their nursing curriculum to address patient
      questions and provide resources. One mechanism to address this knowledge deficit
      is the incorporation of a genetics-based curriculum into nurse residency
      programs. This article describes a novel genetics-based curriculum designed and
      implemented in the UCLA Health System Nurse Residency Program. J Contin Educ
      Nurs. 2017;48(8):379-384.

PMID- 28759698
TI  - What is "the unconscious," and where is it located in the brain? A
      neuropsychoanalytic perspective.
AB  - This is a brief overview of my "neuropsychoanalytic" perspective on the
      unconscious. It should make clear how much psychoanalysis has to gain from
      incorporating the findings of neuroscientific disciplines studying the same part
      of nature-the workings of the human mind. I hope it makes equally clear what
      useful new perspectives can be cast on current issues in cognitive neuroscience,
      if they, in turn, incorporate the findings of psychoanalysis.

PMID- 28759699
TI  - Joint principal trend analysis for longitudinal high-dimensional data.
AB  - We consider a research scenario motivated by integrating multiple sources of
      information for better knowledge discovery in diverse dynamic biological
      processes. Given two longitudinal high-dimensional datasets for a group of
      subjects, we want to extract shared latent trends and identify relevant features.
      To solve this problem, we present a new statistical method named as joint
      principal trend analysis (JPTA). We demonstrate the utility of JPTA through
      simulations and applications to gene expression data of the mammalian cell cycle
      and longitudinal transcriptional profiling data in response to influenza viral
      infections.

PMID- 28759700
TI  - Interventions for treating intrahepatic cholestasis in people with sickle cell
      disease.
AB  - BACKGROUND: Sickle cell disease is the most common hemoglobinopathy occurring
      worldwide and sickle cell intrahepatic cholestasis is a complication long
      recognized in this population. Cholestatic liver diseases are characterized by
      impaired formation or excretion (or both) of bile from the liver. There is a need
      to assess the clinical benefits and harms of the interventions used to treat
      intrahepatic cholestasis in people with sickle cell disease. This is an update of
      a previously published Cochrane Review. OBJECTIVES: To assess the benefits and
      harms of the interventions for treating intrahepatic cholestasis in people with
      sickle cell disease. SEARCH METHODS: We searched the Cystic Fibrosis and Genetic
      Disorders Group's Haemoglobinopathies Trials Register, which comprises references
      identified from comprehensive electronic database searches and handsearching of
      relevant journals and abstract books of conference proceedings. We also searched
      the LILACS database (1982 to 23 May 2017), the WHO International Clinical Trials
      Registry Platform Search Portal (23 May 2017) and ClinicalTrials.gov.Date of last
      search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's
      Haemoglobinopathies Trials Register: 12 April 2017. SELECTION CRITERIA: We
      searched for published or unpublished randomised controlled trials. DATA
      COLLECTION AND ANALYSIS: Each author intended to independently extract data and
      assess the risk of bias of the trials by standard Cochrane methodologies;
      however, no trials were included in the review. MAIN RESULTS: There were no
      randomised controlled trials identified. AUTHORS' CONCLUSIONS: This updated
      Cochrane Review did not identify any randomised controlled trials assessing
      interventions for treating intrahepatic cholestasis in people with sickle cell
      disease. Randomised controlled trials are needed to establish the optimum
      treatment for this condition.

PMID- 28759701
TI  - Pharmacological interventions for preventing dry mouth and salivary gland
      dysfunction following radiotherapy.
AB  - BACKGROUND: Salivary gland dysfunction is an 'umbrella' term for the presence of
      either xerostomia (subjective sensation of dryness), or salivary gland
      hypofunction (reduction in saliva production). It is a predictable side effect of
      radiotherapy to the head and neck region, and is associated with a significant
      impairment of quality of life. A wide range of pharmacological interventions,
      with varying mechanisms of action, have been used for the prevention of radiation
      induced salivary gland dysfunction. OBJECTIVES: To assess the effects of
      pharmacological interventions for the prevention of radiation-induced salivary
      gland dysfunction. SEARCH METHODS: Cochrane Oral Health's Information Specialist
      searched the following databases: Cochrane Oral Health's Trials Register (to 14
      September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL;
      2016, Issue 8) in the Cochrane Library (searched 14 September 2016); MEDLINE Ovid
      (1946 to 14 September 2016); Embase Ovid (1980 to 14 September 2016); CINAHL
      EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 14
      September 2016); LILACS BIREME Virtual Health Library (Latin American and
      Caribbean Health Science Information database; 1982 to 14 September 2016); Zetoc
      Conference Proceedings (1993 to 14 September 2016); and OpenGrey (1997 to 14
      September 2016). We searched the US National Institutes of Health Ongoing Trials
      Register (ClinicalTrials.gov) and the World Health Organization International
      Clinical Trials Registry Platform for ongoing trials. No restrictions were placed
      on the language or date of publication when searching the electronic databases.
      SELECTION CRITERIA: We included randomised controlled trials, irrespective of
      their language of publication or publication status. Trials included participants
      of all ages, ethnic origin and gender, scheduled to receive radiotherapy on its
      own or in addition to chemotherapy to the head and neck region. Participants
      could be outpatients or inpatients. We included trials comparing any
      pharmacological agent regimen, prescribed prophylactically for salivary gland
      dysfunction prior to or during radiotherapy, with placebo, no intervention or an
      alternative pharmacological intervention. Comparisons of radiation techniques
      were excluded. DATA COLLECTION AND ANALYSIS: We used standard methodological
      procedures expected by Cochrane. MAIN RESULTS: We included 39 studies that
      randomised 3520 participants; the number of participants analysed varied by
      outcome and time point. The studies were ordered into 14 separate comparisons
      with meta-analysis only being possible in three of those.We found low-quality
      evidence to show that amifostine, when compared to a placebo or no treatment
      control, might reduce the risk of moderate to severe xerostomia (grade 2 or
      higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95%
      confidence interval (CI) 0.19 to 0.67; P = 0.001, 3 studies, 119 participants),
      and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P =
      0.01, 5 studies, 687 participants), but there is insufficient evidence that the
      effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to
      1.23; P = 0.21, 7 studies, 682 participants). We found very low-quality evidence
      that amifostine increased unstimulated salivary flow rate up to 12 months after
      radiotherapy, both in terms of mg of saliva per 5 minutes (mean difference (MD)
      0.32, 95% CI 0.09 to 0.55; P = 0.006, 1 study, 27 participants), and incidence of
      producing greater than 0.1 g of saliva over 5 minutes (RR 1.45, 95% CI 1.13 to
      1.86; P = 0.004, 1 study, 175 participants). However, there was insufficient
      evidence to show a difference when looking at stimulated salivary flow rates.
      There was insufficient (very low-quality) evidence to show that amifostine
      compromised the effects of cancer treatment when looking at survival measures.
      There was some very low-quality evidence of a small benefit for amifostine in
      terms of quality of life (10-point scale) at 12 months after radiotherapy (MD
      0.70, 95% CI 0.20 to 1.20; P = 0.006, 1 study, 180 participants), but
      insufficient evidence at the end of and up to three months postradiotherapy. A
      further study showed no evidence of a difference at 6, 12, 18 and 24 months
      postradiotherapy. There was low-quality evidence that amifostine is associated
      with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, 5
      studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P =
      0.0002, 3 studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P <
      0.00001, 4 studies, 556 participants); and allergic response (RR 7.51, 95% CI
      1.40 to 40.39; P = 0.02, 3 studies, 524 participants).We found insufficient
      evidence (that was of very low quality) to determine whether or not pilocarpine
      performed better or worse than a placebo or no treatment control for the
      outcomes: xerostomia, salivary flow rate, survival, and quality of life. There
      was some low-quality evidence that pilocarpine was associated with an increase in
      sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, 5 studies, 389
      participants).We found insufficient evidence to determine whether or not
      palifermin performed better or worse than placebo for: xerostomia (low quality);
      survival (moderate quality); and any adverse effects.There was also insufficient
      evidence to determine the effects of the following interventions: biperiden plus
      pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium,
      antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse, and
      Venalot Depot (coumarin plus troxerutin). AUTHORS' CONCLUSIONS: There is some low
      quality evidence to suggest that amifostine prevents the feeling of dry mouth in
      people receiving radiotherapy to the head and neck (with or without chemotherapy)
      in the short- (end of radiotherapy) to medium-term (three months
      postradiotherapy). However, it is less clear whether or not this effect is
      sustained to 12 months postradiotherapy. The benefits of amifostine should be
      weighed against its high cost and side effects. There was insufficient evidence
      to show that any other intervention is beneficial.

PMID- 28759702
TI  - Protective effect of proanthocyanidins against doxorubicin-induced nephrotoxicity
      in rats.
AB  - Doxorubicin (DOX) exerts toxic effects in several organs particularly kidney. The
      present study aimed to assess the protective effect of proanthocyanidins (PAs)
      against DOX-induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg,
      i.v.) significantly increased kidney weight, kidney/body weight ratio, serum
      urea, creatinine, tumor necrosis factor alpha levels, and kidney contents of
      malondialdehyde, nitric oxide, cyclooxygenase-2, and caspase-3 activity with
      significant reduction in final body weight, serum albumin, kidney contents of
      reduced glutathione (GSH), and superoxide dismutase activity as compared with
      control group. In contrast, pretreatment with PAs (200 mg/kg, p.o.) for 14 days
      before DOX and for 7 days after DOX ameliorated kidney function and oxidative
      stress parameters. Histopathological evidence confirmed the protective effects of
      PAs from the tissue damage induced by DOX. In conclusion, PAs have a multi
      nephroprotective effect that might be attributed to its antioxidant, anti
      inflammatory, and antiapoptoic activities.

PMID- 28759703
TI  - Extracorporeal shock wave treatment can selectively destroy end plates in
      neuromuscular junctions.
AB  - INTRODUCTION: This study assesses the effect of radial extracorporeal shock wave
      (rESW) exposure on neuromuscular transmission and neuromuscular junction (NMJ)
      morphology. METHODS: We applied 2,000 rESWs at 0.18 mJ/mm2 and a frequency of 15
      Hz to the right calf of male rats, measured the compound muscle action potential
      (CMAP), and examined NMJ morphology using electron microscopy. Left calf muscles
      were used as controls. RESULTS: rESW exposure significantly reduced CMAP
      amplitude without delayed latency in exposed muscles compared with controls. All
      rESW-exposed muscles exhibited NMJs with irregular end plates. Mean
      interjunctional fold interval was significantly increased compared with controls.
      However, axon terminals and muscle fibers surrounding NMJs with irregular end
      plates were unchanged. DISCUSSION: This localized destruction of end plates may
      be caused by differences in acoustic impedance induced by the density of
      acetylcholine receptors. These results provide a possible mechanism for the
      effectiveness of rESW treatment for spasticity and dystonia. Muscle Nerve 57: 466
      472, 2018.

PMID- 28759704
TI  - Intrahepatic cholangiocarcinoma arising from HBV infection may be a highly
      selected population for liver transplantation.

PMID- 28759705
TI  - Validation of clay modeling as a learning tool for the periventricular structures
      of the human brain.
AB  - Visualizing anatomical structures and functional processes in three dimensions
      (3D) are important skills for medical students. However, contemplating 3D
      structures mentally and interpreting biomedical images can be challenging. This
      study examines the impact of a new pedagogical approach to teaching neuroanatomy,
      specifically how building a 3D-model from oil-based modeling clay affects
      learners' understanding of periventricular structures of the brain among
      undergraduate medical students in Colombia. Students were provided with an
      instructional video before building the models of the structures, and thereafter
      took a computer-based quiz. They then brought their clay models to class where
      they answered questions about the structures via interactive response cards.
      Their knowledge of periventricular structures was assessed with a paper-based
      quiz. Afterward, a focus group was conducted and a survey was distributed to
      understand students' perceptions of the activity, as well as the impact of the
      intervention on their understanding of anatomical structures in 3D. Quiz scores
      of students that constructed the models were significantly higher than those
      taught the material in a more traditional manner (P < 0.05). Moreover, the
      modeling activity reduced time spent studying the topic and increased
      understanding of spatial relationships between structures in the brain. The
      results demonstrated a significant difference between genders in their self
      perception of their ability to contemplate and rotate structures mentally (P <
      0.05). The study demonstrated that the construction of 3D clay models in
      combination with autonomous learning activities was a valuable and efficient
      learning tool in the anatomy course, and that additional models could be designed
      to promote deeper learning of other neuroanatomy topics. Anat Sci Educ 11: 137
      145. (c) 2017 American Association of Anatomists.

PMID- 28759706
TI  - Reply.

PMID- 28759707
TI  - Relevance of cystatin-C, N-acetylglucosaminidase, and Interleukin-18 with the
      diagnosis of acute kidney injury induced by cadmium in rats.
AB  - The diagnosis of acute kidney injury (AKI) is frequently established on
      modifications in serum creatinine (SCr). The discriminative and prognostic
      aptitudes of serum cystatin-C as well as N-acetylglucosaminidase (NAG) and
      Interleukin-18 (IL-18) were inspected for the estimation of AKI. In this study
      twelve rats were alienated into two groups: control group received saline, second
      group received cadmium chloride at a dose (2.4 mg Cd/kg/day, i.p) for 30 days.
      Blood urea nitrogen (BUN), SCr, and IL-18 serum level were measured in addition
      to serum and tissue content of cystatin-C and NAG. AKI model showed significant
      increase in BUN, creatinine, and IL-18. RT-PCR showed upregulation of cystatin-C
      gene besides significant increase of its level in serum. Additionally, tissue
      content of NAG was significantly increased. Our findings may provide that
      grouping of several biomarkers for diagnosis of AKI is a more valuable diagnostic
      tool than single-marker measurement.

PMID- 28759708
TI  - Methods for including information from multi-arm trials in pairwise meta
      analysis.
AB  - Systematic reviewers conducting pairwise meta-analyses sometimes encounter multi
      arm studies. To include these studies, and to avoid a unit-of-analysis error,
      often two or more arms are combined or the control arm is split. In this
      tutorial, we present 5 different approaches that can be used. Particularly, we
      present a novel approach (method 4) that to the best of our knowledge has not
      been presented before. We demonstrate their application on 3 selected data sets,
      discuss their scope of application and their advantages and limitations, and give
      recommendations.

PMID- 28759709
TI  - Reconstruction method as an independent risk factor for postoperative bone
      mineral density loss in gastric cancer.
AB  - BACKGROUND AND AIM: No study has compared the incidence of postoperative bone
      metabolic disorders between Billroth-I (B-I) and Roux-en-Y (R-Y) reconstructions
      after distal gastrectomy (DG) for gastric cancer (GC). In this study, we wished
      to examine the impact of reconstruction method on postoperative bone mineral
      density (BMD) loss. METHODS: We investigated a total of 148 consecutive patients
      who underwent DG with B-I or R-Y reconstruction for stage I GC between 2008 and
      2012. We retrospectively assessed the BMD data using computed tomography
      attenuation values of the first lumbar vertebra after surgery. RESULTS: In
      multivariate analysis for the whole study series, R-Y reconstruction was
      identified as an independent risk factor for BMD loss after DG (P < 0.0001; OR =
      5.60; 95% CI = 2.38-13.98). Propensity score match analysis was used to overcome
      bias because of the different covariates for the two groups; even though the 37
      patients in the B-I group and the 37 patients in the R-Y group had no significant
      difference among characteristics, B-I reconstruction was validated to have
      superiority over R-Y reconstruction for preventing BMD loss in the first 3 years
      after DG. The cumulative hazard ratio of osteoporosis after gastrectomy was
      significantly higher in the R-Y group than in the B-I group (P = 0.0427).
      CONCLUSIONS: Billroth-I reconstruction might be a preferable method for
      preventing BMD loss after gastrectomy in GC patients.

PMID- 28759711
TI  - What is a "unimodal" cell population? Using statistical tests as criteria for
      unimodality in automated gating and quality control.
AB  - Many automated gating algorithms for flow cytometry data are based on the concept
      of unimodal cell populations. However, in this article, we show that criteria
      previously used to make decisions on unimodality cannot adequately distinguish
      unimodal from bimodal densities. We show that dip and bandwidth tests for
      unimodality, taken from the statistics literature, can do this with consistent
      and low error rates. These tests also have the possibility to adjust the
      significance level to handle the trade-off between failing to detect a second
      mode and seeing a second mode when there is none. The differences between the dip
      and bandwidth tests are elucidated using real data from the FlowCAP I challenge,
      also guidelines for flow cytometry data preprocessing are given. (c) 2017
      International Society for Advancement of Cytometry.

PMID- 28759710
TI  - Functional integrity in children with anoxic brain injury from drowning.
AB  - Drowning is a leading cause of accidental injury and death in young children.
      Anoxic brain injury (ABI) is a common consequence of drowning and can cause
      severe neurological morbidity in survivors. Assessment of functional status and
      prognostication in drowning victims can be extremely challenging, both acutely
      and chronically. Structural neuroimaging modalities (CT and MRI) have been of
      limited clinical value. Here, we tested the utility of resting-state functional
      MRI (rs-fMRI) for assessing brain functional integrity in this population. Eleven
      children with chronic, spastic quadriplegia due to drowning-induced ABI were
      investigated. All were comatose immediately after the injury and gradually
      regained consciousness, but with varying ability to communicate their cognitive
      state. Eleven neurotypical children matched for age and gender formed the control
      group. Resting-state fMRI and co-registered T1-weighted anatomical MRI were
      acquired at night during drug-aided sleep. Network integrity was quantified by
      independent components analysis (ICA), at both group- and per-subject levels.
      Functional-status assessments based on in-home observations were provided by
      families and caregivers. Motor ICNs were grossly compromised in ABI patients both
      group-wise and individually, concordant with their prominent motor deficits.
      Striking preservations of perceptual and cognitive ICNs were observed, and the
      degree of network preservation correlated (rho = 0.74) with the per-subject
      functional status assessments. Collectively, our findings indicate that rs-fMRI
      has promise for assessing brain functional integrity in ABI and, potentially, in
      other disorders. Furthermore, our observations suggest that the severe motor
      deficits observed in this population can mask relatively intact perceptual and
      cognitive capabilities. Hum Brain Mapp 38:4813-4831, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28759712
TI  - Mechanisms of action of nonpeptide hormones on resveratrol-induced
      antiproliferation of cancer cells.
AB  - Nonpeptide hormones, such as thyroid hormone, dihydrotestosterone, and estrogen,
      have been shown to stimulate cancer proliferation via different mechanisms. Aside
      from their cytosolic or membrane-bound receptors, there are receptors on integrin
      alphav beta3 for nonpeptide hormones. Interaction between hormones and integrin
      alphav beta3 can induce signal transduction and eventually stimulate cancer cell
      proliferation. Resveratrol induces inducible COX-2-dependent antiproliferation
      via integrin alphav beta3 . Resveratrol and hormone-induced signals are both
      transduced by activated extracellular-regulated kinases 1 and 2 (ERK1/2);
      however, hormones promote cell proliferation, while resveratrol induces
      antiproliferation in cancer cells. Hormones inhibit resveratrol-stimulated
      phosphorylation of p53 on Ser15, resveratrol-induced nuclear COX-2 accumulation,
      and formation of p53-COX-2 nuclear complexes. Subsequently, hormones impair
      resveratrol-induced COX-2-/p53-dependent gene expression. The inhibitory effects
      of hormones on resveratrol action can be blocked by different antagonists of
      specific nonpeptide hormone receptors but not integrin alphav beta3 blockers.
      Results suggest that nonpeptide hormones inhibit resveratrol-induced
      antiproliferation in cancer cells downstream of the interaction between ligand
      and receptor and ERK1/2 activation to interfere with nuclear COX-2 accumulation.
      Thus, the surface receptor sites for resveratrol and nonpeptide hormones are
      distinct and can induce discrete ERK1/2-dependent downstream antiproliferation
      biological activities. It also indicates the complex pathways by which
      antiproliferation is induced by resveratrol in various physiological hormonal
      environments. .

PMID- 28759713
TI  - Some metals inhibit the glutathione S-transferase from Van Lake fish gills.
AB  - Glutathione S-transferases (GSTs) are the superfamily of multifunctional
      detoxification isoenzymes and play important role cellular signaling. The present
      article focuses on the role of Cd2+ , Cu2+ , Zn2+ , and Ag+ in vitro inhibition
      of GST. For this purpose, GST was purified from Van Lake fish (Chalcalburnus
      tarichii Pallas) gills with 110.664 EU mg-1 specific activity and 79.6% yield
      using GSH-agarose affinity chromatographic method. The metal ions were tested at
      various concentrations on in vitro GST activity. IC50 values were found for Cd+2
      , Cu+2 , Zn+2 , Ag+ as 450.32, 320.25, 1510.13, and 16.43 MUM, respectively. Ki
      constants were calculated as 197.05 +/- 105.23, 333.10 +/- 152.76, 1670.21 +/-
      665.43, and 0.433 +/- 0.251 MUM, respectively. Ag+ showed better inhibitory
      effect compared with the other metal ions. The inhibition mechanisms of Cd2+ and
      Cu2+ were non-competitive, whereas Zn2+ and Ag+ were competitive. Co2+ , Cr2+ ,
      Pb2+ , and Fe3+ had no inhibitory activity on GST.

PMID- 28759714
TI  - Rationally Designed Self-Healing Hydrogel Electrolyte toward a Smart and
      Sustainable Supercapacitor.
AB  - Excellent self-healability and renewability are crucial for the development of
      wearable/flexible energy-storage devices aiming for advanced personalized
      electronics. However, realizing low-temperature self-healing and harmless
      regeneration remains a big challenge for existing wearable/flexible energy
      storage devices, which is fundamentally limited by conventional polymeric
      electrolytes that are intrinsically neither cryo-healable nor renewable. Here, we
      rationally design a multifunctional polymer electrolyte on the basis of the
      copolymer of vinylimidazole and hydroxypropyl acrylate, which exhibits all
      features solving the above-mentioned limitations. A supercapacitor comprising the
      electrolyte autonomously restores its electrochemical behaviors at temperatures
      ranging from 25 to -15  degrees C after multiple mechanical breakings.
      Interestingly, it is even able to regenerate for 5 cycles through a simple
      wetting process in the case of malfunction, while maintaining its capacitive
      properties and excellent self-healability. Our investigation provides a novel
      insight into designing smart and sustainable energy-storage devices that might be
      applied to intelligent apparel, electronic skin or flexible robot, and so on.

PMID- 28759715
TI  - Strong Surface Hydrophilicity in Co-Based Electrocatalysts for Water Oxidation.
AB  - Developing efficient and durable oxygen evolution electrocatalyst is of paramount
      importance for the large-scale supply of renewable energy sources. Herein, we
      report the design of significant surface hydrophilicity based on cobalt
      oxyhydroxide (CoOOH) nanosheets to greatly improve the surface hydroxyl species
      adsorption and reaction kinetics at the Helmholtz double layer for high
      efficiency water oxidation activity. The as-designed CoOOH-graphene nanosheets
      achieve a small surface water contact angle of ~23 degrees  and a large double
      layer capacitance (Cdl) of 8.44 mF/cm2 and thus could evidently strengthen
      surface species adsorption and trigger electrochemical oxygen evolution reaction
      (OER) under a quite low onset potential of 200 mV with an excellent Tafel slope
      of 32 mV/dec. X-ray absorption spectroscopy and first-principles calculations
      demonstrate that the strong interface electron coupling between CoOOH and
      graphene extracts partial electrons from the active sties and increases the
      electron state density around the Fermi level and effectively promotes the
      surface intermediates formation for efficient OER.

PMID- 28759716
TI  - Thiol-Dependent Reduction of the Triester and Triamide Derivatives of Finland
      Trityl Radical Triggers O2-Dependent Superoxide Production.
AB  - Tetrathiatriaylmethyl (trityl) radicals have found wide biomedical applications
      as magnetic resonance probes. Trityl radicals and their derivatives are generally
      stable toward biological reducing agents such as glutathione (GSH) and ascorbate.
      We demonstrate that the triester (ET-03) and triamide (AT-03) derivatives of the
      Finland trityl radical exhibit unique reduction by thiols such as GSH and
      cysteine (Cys) to generate the corresponding trityl carbanions as evidenced by
      the loss of EPR signal and appearance of characteristic UV-vis absorbance at 644
      nm under anaerobic conditions. The trityl carbanions can be quickly converted
      back to the original trityl radicals by oxygen (O2) in air, thus rendering the
      reaction between the trityl derivative and biothiol undetectable under aerobic
      conditions. The reduction product of O2 by the trityl carbanions was shown to be
      superoxide radical (O2*-) by EPR spin-trapping. Kinetic studies showed that the
      reaction rate constants (k) depend on the types of both trityl radicals and
      thiols with the order of kET-03/Cys (0.336 M-1 s-1) > kET-03/GSH (0.070 M-1 s-1)
      > kAT-03/Cys (0.032 M-1 s-1) > kAT-03/GSH (0.027 M-1 s-1). The reactivity of
      trityl radicals with thiols is closely related to the para-substituents of trityl
      radicals as well as the pKa of the thiols and is further reflected by the rate of
      O2*- production and consumptions of O2 and thiols. This novel reaction represents
      a new metabolic process of trityl derivatives and should be considered in the
      design and application of new trityl radical probes.

PMID- 28759717
TI  - Mode of Action (MOA) Assignment Classifications for Ecotoxicology: An Evaluation
      of Approaches.
AB  - The mode of toxic action (MOA) is recognized as a key determinant of chemical
      toxicity and as an alternative to chemical class-based predictive toxicity
      modeling. However, MOA classification has never been standardized in
      ecotoxicology, and a comprehensive comparison of classification tools and
      approaches has never been reported. Here we critically evaluate three MOA
      classification methodologies using an aquatic toxicity data set of 3448
      chemicals, compare the approaches, and assess utility and limitations in
      screening and early tier assessments. The comparisons focused on three commonly
      used tools: Verhaar prediction of toxicity MOA, the U.S. Environmental Protection
      Agency (EPA) ASsessment Tool for Evaluating Risk (ASTER) QSAR (quantitative
      structure activity relationship) application, and the EPA Mode of Action and
      Toxicity (MOAtox) database. Of the 3448 MOAs predicted using the Verhaar scheme,
      1165 were classified by ASTER, and 802 were available in MOAtox. Of the subset of
      432 chemicals with MOA assignments for each of the three schemes, 42% had
      complete concordance in MOA classification, and there was no agreement for 7% of
      the chemicals. The research shows the potential for large differences in MOA
      classification between the five broad groups of the Verhaar scheme and the more
      mechanism-based assignments of ASTER and MOAtox. Harmonization of classification
      schemes is needed to use MOA classification in chemical hazard and risk
      assessment more broadly.

PMID- 28759718
TI  - Temperature-Dependent Hole Transfer from Photoexcited Quantum Dots to Molecular
      Species: Evidence for Trap-Mediated Transfer.
AB  - The effect of temperature on the rate of hole transfer from photoexcited quantum
      dots (QDs) is investigated by measuring the driving force dependence of the
      charge transfer rate for different sized QDs across a range of temperatures from
      78 to 300 K. Spherical CdSe/CdS core/shell QDs were used with a series of
      ferrocene-derived molecular hole acceptors with an 800 meV range in
      electrochemical potential. Time-resolved photoluminescence measurements and
      photoluminescence quantum yield measurements in an integrating sphere were both
      performed from 78 to 300 K to obtain temperature-dependent rates for a series of
      driving forces as dictated by the nature of the molecular acceptor. For both QD
      sizes studied and all ligands, the Arrhenius plot of hole transfer exhibited an
      activated (linear) regime at higher temperatures and a temperature-independent
      regime at low temperatures. The extracted activation energies in the high
      temperature regime were consistent across all ligands for a given QD size. This
      observation is not consistent with direct charge transfer from the QD valence
      band to the ferrocene acceptor. Instead, a model in which charge transfer is
      mediated by a shallow and reversible trap more accurately fits the experimental
      results. Implications for this observed trap-mediated transfer are discussed
      including as a strategy to more efficiently extract charge from QDs.

PMID- 28759719
TI  - Finke-Watzky Two-Step Nucleation-Autocatalysis Model of S100A9 Amyloid Formation:
      Protein Misfolding as "Nucleation" Event.
AB  - Quantitative kinetic analysis is critical for understanding amyloid mechanisms.
      Here we demonstrate the application of generic Finke-Watzky (F-W) two-step
      nucleation-autocatalytic growth model to the concentration-dependent amyloid
      kinetics of proinflammatory alpha-helical S100A9 protein at pH 7.4 and at 37 and
      42  degrees C. The model is based on two pseudoelementary reaction steps applied
      without further analytical constraints, and its treatment of S100A9 amyloid self
      assembly demonstrates that initial misfolding and beta-sheet formation, defined
      as "nucleation" step, spontaneously takes place within individual S100A9
      molecules at higher rate than the subsequent fibrillar growth. The latter,
      described as an autocatalytic process, will proceed if misfolded amyloid-prone
      S100A9 is populated on a macroscopic time scale. Short lengths of S100A9 fibrils
      are consistent with the F-W model. The analysis of fibrillar length distribution
      by the Beker-Doring model demonstrates independently that such distribution is
      solely determined by slow fibril growth and there is no fragmentation or
      secondary pathways decreasing fibrillar length.

PMID- 28759720
TI  - Tilt Grain Boundary Topology Induced by Substrate Topography.
AB  - Synthesis of two-dimensional (2D) crystals is a topic of great current interest,
      since their chemical makeup, electronic, mechanical, catalytic, and optical
      properties are so diverse. A universal challenge, however, is the generally
      random formation of defects caused by various growth factors on flat surfaces.
      Here we show through theoretical analysis and experimental demonstration that
      nonplanar, curved-topography substrates permit the intentional and controllable
      creation of topological defects within 2D materials. We augment a common phase
      field method by adding a geometric phase to track the crystal misorientation on a
      curved surface and to detect the formation of grain boundaries, especially when a
      growing monocrystal "catches its own tail" on a nontrivial topographical feature.
      It is specifically illustrated by simulated growth of a trigonal symmetry crystal
      on a conical-planar substrate, to match the experimental synthesis of WS2 on
      silicon template, with satisfactory and in some cases remarkable agreement of
      theory predictions and experimental evidence.

PMID- 28759721
TI  - Microchip Circulation Drastically Accelerates Amyloid Aggregation of 1-42 beta
      amyloid Peptide from Felis catus.
AB  - The amyloid aggregation process of amyloid beta1-42 peptide is responsible for
      Alzheimer's disease, affecting millions of elderly people worldwide. Although
      there has been a great deal of attention directed toward tackling this disease,
      still no medicine has been found for this fatal disorder. To address this
      challenge, it is vital to thoroughly understand the molecular mechanism
      underlying the amyloid peptide aggregation process, as well as seek substances
      that could hamper this aggregation. In order to shed light on mechanisms leading
      to amyloidogenesis, we employed a microfluidic system to determine the possible
      influence of in vivo-like flow in the microchip channel itself on feline Abeta1
      42 peptide amyloidogenesis. We have shown that shear forces occurring during such
      flow immensely accelerated peptide aggregation. We also tested the inhibitory
      influence of 3,3'-[1,6-(2,5-dioxahexane)]bis(1-dodecylimidazolium) dichloride
      gemini surfactant on peptide amyloidogenesis. Our results suggest that this
      surfactant may inhibit amyloid beta1-42 fibril formation.

PMID- 28759722
TI  - Perturbation in Long-Range Contacts Modulates the Kinetics of Amyloid Formation
      in alpha-Synuclein Familial Mutants.
AB  - The characteristic cross-beta-sheet-rich amyloid fibril formation by
      intrinsically disordered alpha-synuclein proteins is one of the pathological
      hallmarks of Parkinson's disease. Although unstructured in solution, the presence
      of autoinhibitory long-range contacts in monomeric form prevents protein
      aggregation. Out of the various factors that affect the rate of amyloid
      formation, familial mutations play an important role in alpha-synuclein
      aggregation. Even though these mutations are believed to form an aggregation
      prone intermediate by perturbing these contacts, the correlation between
      perturbation and rate of fibril formation is not very straightforward. A
      combination of solution and solid-state NMR in conjunction with other biophysical
      methods has been used to identify the underlying mechanism behind the anomaly in
      the rate of aggregation for the novel mutants H50Q (fast aggregating) and G51D
      (slow aggregating). Perturbation of long-range contacts at the mutation sites and
      C-termini in all of the six familial mutants of alpha-synuclein during the
      diseased condition (acidic pH) was observed. These contacts get rearranged at
      physiological pH resulting in the shielding of mutation sites. Additional
      contacts at the mutation site in a slow aggregating mutant could be the reason
      for slower aggregation. Indeed, these contacts provide more rigidity to the
      monomeric G51D. Nonetheless, these mutations did not alter the overall secondary
      structure. The differential pattern of the long-range contacts at the monomeric
      level resulted in the perturbation of the fibrillar-core region, which was
      evident in the solid-state NMR spectra. Our results provide valuable insights in
      understanding the effect of long-range contacts on the aggregation of alpha
      synuclein and its mutants.

PMID- 28759723
TI  - Physiological and Transcriptomic Analysis Validates Previous Findings of Changes
      in Primary Metabolism for the Production of Phenolic Antioxidants in Wounded
      Carrots.
AB  - Wounding induces the accumulation of phenolic compounds in carrot. This study
      uses physiological and transcriptomic analysis to validate previous findings
      relating primary metabolism and secondary metabolites in wounded carrots. Our
      data confirmed that increased wounding intensity strengthened the accumulation of
      phenolics accompanied by enhancing respiration and showed the loss of fructose
      and glucose and the increase of energy status in carrots. In addition,
      transcriptomic evaluation of shredded carrots indicated that the respiratory
      metabolism, sugar metabolism, energy metabolism, and phenolic biosynthesis
      related pathways, such as "citrate cycle (TCA cycle)", "oxidative
      phosphorylation" and "phenylpropanoid biosynthesis", were activated by wounding.
      Also, the differentially expressed genes (DEGs) involved in the conversion of
      sugars to phenolics were extensively up-regulated after wounding. Thus, the
      physiological and transcriptomic data validate previous findings that wounding
      accelerates the primary metabolisms of carrot including respiratory metabolism,
      sugar metabolism, and energy metabolism to meet the demand for the production of
      phenolic antioxidants.

PMID- 28759724
TI  - Enantioselective Alkynylation of Aromatic Aldehydes Catalyzed by a Sterically
      Highly Demanding Chiral-at-Rhodium Lewis Acid.
AB  - The enantioselective catalytic alkynylation of aromatic aldehydes is reported
      using a sterically highly hindered bis-cyclometalated rhodium-based Lewis acid
      catalyst featuring the octahedral metal as the only stereogenic center. Yields of
      58-98% with 79-98% enantiomeric excess were achieved using 1-2 mol % of catalyst.
      This work complements previous work from our laboratory on the enantioselective
      alkynylation of 2-trifluoroacetyl imidazoles (Chem. - Eur. J. 2016, 22, 11977
      11981) and trifluoromethyl ketones (J. Am. Chem. Soc. 2017, 139, 4322-4325) using
      catalysts with octahedral metal-centered chirality.

PMID- 28759725
TI  - Strong Deformation of the Thick Electric Double Layer around a Charged Particle
      during Sedimentation or Electrophoresis.
AB  - The deformation of the electric double layer around a charged colloidal particle
      during sedimentation or electrophoresis in a binary, symmetric electrolyte is
      studied. The surface potential of the particle is assumed to be small compared to
      the thermal voltage scale. Additionally, the Debye length is assumed to be large
      compared to the particle size. These assumptions enable a linearization of the
      electrokinetic equations. The particle appears as a point charge in this thick
      double-layer limit; the distribution of charge in the diffuse cloud surrounding
      it is determined by a balance of advection due to the particle motion, Brownian
      diffusion of ions, and electrostatic screening of the particle by the cloud. The
      ability of advection to deform the charge cloud from its equilibrium state is
      parametrized by a Peclet number, Pe. For weak advection (Pe ? 1), the cloud is
      only slightly deformed. In contrast, the cloud can be completely stripped from
      the particle at Pe ? 1; consequently, electrokinetic effects on the particle
      motion vanish in this regime. Therefore, in sedimentation the drag limits to
      Stokes' law for an uncharged particle as Pe -> infinity. Likewise, the particle
      velocity for electrophoresis approaches Huckel's result. The strongly deformed
      cloud at large Pe is predicted to generate a concomitant increase in the
      sedimentation field in a dilute settling suspension.

PMID- 28759726
TI  - Inorganic Nanoparticles as Donors in Resonance Energy Transfer for Solid-Phase
      Bioassays and Biosensors.
AB  - Bioassays for the rapid detection and quantification of specific nucleic acids,
      proteins, and peptides are fundamental tools in many clinical settings.
      Traditional optical emission methods have focused on the use of molecular dyes as
      labels to track selective binding interactions and as probes that are sensitive
      to environmental changes. Such dyes can offer good detection limits based on
      brightness but typically have broad emission bands and suffer from time-dependent
      photobleaching. Inorganic nanoparticles such as quantum dots and upconversion
      nanoparticles are photostable over prolonged exposure to excitation radiation and
      tend to offer narrow emission bands, providing a greater opportunity for
      multiwavelength multiplexing. Importantly, in contrast to molecular dyes,
      nanoparticles offer substantial surface area and can serve as platforms to carry
      a large number of conjugated molecules. The surface chemistry of inorganic
      nanoparticles offers both challenges and opportunities for the control of
      solubility and functionality for selective molecular interactions by the assembly
      of coatings through coordination chemistry. This report reviews advances in the
      compositional design and methods of conjugation of inorganic quantum dots and
      upconversion nanoparticles and the assembly of combinations of nanoparticles to
      achieve energy exchange. Our interest is the exploration of configurations where
      the modified nanoparticles can be immobilized to solid substrates for the
      development of bioassays and biosensors that operate by resonance energy transfer
      (RET).

PMID- 28759727
TI  - The beneficial effects of resveratrol on steatosis and mitochondrial oxidative
      stress in HepG2 cells.
AB  - Nonalcoholic fatty liver disease (NAFLD) is currently one of the most common
      chronic liver diseases, especially in developed countries. One group of
      substances with a potential use in the treatment of NAFLD are plant polyphenols,
      represented by resveratrol. The aim of this study was to evaluate the effect of
      resveratrol on steatosis and oxidative stress in HepG2 cells. The steatosis of
      cells was carried out using free fatty acids: oleic or palmitic acid and their
      mixtures. Steatosis was visualized using the intracellular lipid staining by Nile
      Red dye with a fluorescence microscope. This study also determined the viability
      of cells and mitochondrial membrane potential. The current study showed that
      fatty acids and their mixtures induced fat overloading in HepG2 cells. In the
      group of cells incubated with oleic acid (OA), observed changes were moderate
      with prevailing micro-vesicular steatosis. In case of cells incubated with
      palmitic acid (PA) and the mixtures of fatty acids, micro- and macro-vacuolar
      steatosis occurred in most of the cells. Resveratrol decreased steatosis in HepG2
      cells induced by OA, PA, as well as their mixtures, and in most of experimental
      groups did not reduce cells viability. Resveratrol reduced the oxidative stress
      in HepG2 cells treated with fatty acids mixtures.

PMID- 28759728
TI  - Molecular cytogenetic identification of a wheat - Thinopyrum ponticum
      substitution line with stripe rust resistance.
AB  - Thinopyrum ponticum (Th. ponticum) (2n = 10x = 70) is an important breeding
      material with excellent resistance and stress tolerance. In this study, we
      characterized the derivative line CH1113-B13-1-1-2-1 (CH1113-B13) through
      cytological, morphological, genomic in situ hybridization (GISH), fluorescence in
      situ hybridization (FISH), expressed sequence tag (EST), and PCR-based landmark
      unique gene (PLUG) marker analysis. The GISH analysis revealed that CH1113-B13
      contained 20 pairs of common wheat chromosomes and one pair of JSt genomic
      chromosomes. Linkage analysis of Th. ponticum using seven EST and seven PLUG
      markers indicated that the pair of alien chromosomes belonged to the seventh
      homeologous group. Nulli-tetrasomic and FISH analysis revealed that wheat 7B
      chromosomes were absent in CH1113-B13; thus, CH1113-B13 was identified as a 7JSt
      (7B) substitution line. Finally, adult-stage CH1113-B13 exhibited immunity to
      wheat stripe rust. This substitution line is therefore a promising germplasm
      resource for wheat breeding.

PMID- 28759729
TI  - The Effects of Injury Prevention Programs on the Biomechanics of Landing Tasks: A
      Systematic Review With Meta-analysis.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) tear is a common injury in sports
      and often occurs during landing from a jump. PURPOSE: To synthesize the evidence
      on the effects of injury prevention programs (IPPs) on landing biomechanics as
      they relate to the ligament, quadriceps, trunk, and leg dominance theories
      associated with ACL injury risk. STUDY DESIGN: Meta-analysis. METHODS: Six
      electronic databases were searched for studies that investigated the effect of
      IPPs on landing task biomechanics. Prospective studies that reported landing
      biomechanics at baseline and post-IPP were included. Results from trunk, hip, and
      knee kinematics and kinetics related to the ACL injury theories were extracted,
      and meta-analyses were performed when possible. RESULTS: The criteria were met by
      28 studies with a total of 466 participants. Most studies evaluated young
      females, bilateral landing tasks, and recreational athletes, while most variables
      were related to the ligament and quadriceps dominance theories. An important
      predictor of ACL injury, peak knee abduction moment, decreased ( P = .01) after
      the IPPs while other variables related to the ligament dominance theory did not
      change. Regarding the quadriceps dominance theory, after the IPPs, angles of hip
      flexion at initial contact ( P = .009), peak hip flexion ( P = .002), and peak
      knee flexion ( P = .007) increased, while knee flexion at initial contact did not
      change ( P = .18). Moreover, peak knee flexion moment decreased ( P = .005) and
      peak vertical ground-reaction force did not change ( P = .10). CONCLUSION: The
      exercises used in IPPs might have the potential to improve landing task
      biomechanics related to the quadriceps dominance theory, especially increasing
      peak knee and hip flexion angles. Importantly, peak knee abduction moment
      decreased, which indicates that IPPs influence a desired movement strategy to
      help athletes overcome dangerous ligament dominance loads arising from lack of
      frontal plane control during dynamic tasks. The lack of findings for some
      biomechanical variables suggests that future IPPs may be enhanced by targeting
      participants' baseline profile deficits, highlighting the need to deliver an
      individualized and task-specific IPP.

PMID- 28759730
TI  - Protein-protein cross-linking and human health: the challenge of elucidating with
      mass spectrometry.
AB  - INTRODUCTION: In several biomedical research fields, the cross-linking of
      peptides and proteins has an important impact on health and wellbeing. It is
      therefore of crucial importance to study this class of post-translational
      modifications in detail. The huge potential of mass spectrometric technologies in
      the mapping of these protein-protein cross-links is however overshadowed by the
      challenges that the field has to overcome. Areas covered: In this review, we
      summarize the different pitfalls and challenges that the protein-protein cross
      linking field is confronted with when using mass spectrometry approaches. We
      additionally focus on native disulfide bridges as an example and provide some
      examples of cross-links that are important in the biomedical field. Expert
      commentary: The current flow of methodological improvements, mainly from the
      chemical cross-linking field, has delivered a significant contribution to
      deciphering native and insult-induced cross-links. Although an automated data
      analysis of proteome-wide peptide cross-linking is currently only possible in
      chemical cross-linking experiments, the field is well on the way towards a more
      automated analysis of native and insult-induced cross-links in raw mass
      spectrometry data that will boost its potential in biomedical applications.

PMID- 28759731
TI  - Antibiotic drug piperacillin induces neuron cell death through mitochondrial
      dysfunction and oxidative damage.
AB  - Although nerve damage/toxicity has been shown to be one of the side effects in
      patients given prolonged antibiotic treatment, the mechanisms of the action of
      antibiotics on neuron cells are not clear. In this work, we investigated the
      toxicity of piperacillin (an antibiotic that can penetrate the blood-brain
      barrier) on neuron cells and its underlying mechanisms. We show that clinically
      relevant doses of piperacillin induce apoptosis in SH-SY5Y and human primary
      neuron cells through activating caspase-3 activity and decreasing Mcl-1 and Bcl-2
      levels. In addition, piperacillin causes mitochondrial dysfunction in neuron
      cells as shown by the reduction of mitochondrial respiration, membrane potential,
      and ATP production. We further demonstrate that piperacillin increases
      accumulation of mitochondrial superoxide and reactive oxygen species, suggesting
      the oxidative stress in neuron cells. Consistently, oxidative damage to DNA,
      proteins, and membrane lipids are observed in neuron cells exposed to
      piperacillin. The deleterious effects of piperacillin are abolished in neuron
      cells by antioxidant N-acetyl-l-cysteine, further confirming that piperacillin
      causes neuron cell death through inducing mitochondrial dysfunction and oxidative
      damage. Our work demonstrates the role of piperacillin in inducing oxidative
      damage in neuron cells and also provides a therapeutic strategy to prevent the
      side effects of antibiotic treatment.

PMID- 28759732
TI  - Therapeutic Effects of Doxycycline on the Quality of Repaired and Unrepaired
      Achilles Tendons.
AB  - BACKGROUND: Achilles tendon tears are devastating injuries, especially to
      athletes. Elevated matrix metalloproteinase (MMP) activity after a tendon injury
      has been associated with deterioration of the collagen network and can be
      inhibited with doxycycline (Doxy). HYPOTHESIS: Daily oral administration of Doxy
      will enhance the histological, molecular, and biomechanical quality of transected
      Achilles tendons. Additionally, suture repair will further enhance the quality of
      repaired tendons. STUDY DESIGN: Controlled laboratory study. METHODS: Randomized
      unilateral Achilles tendon transection was performed in 288 adult male Sprague
      Dawley rats. The injured tendons were either unrepaired (groups 1 and 2) or
      surgically repaired (groups 3 and 4). Animals from groups 2 and 4 received Doxy
      daily through oral gavage, and animals from groups 1 and 3 served as controls (no
      Doxy). Tendons were harvested at 1.5, 3, 6, and 9 weeks after the injury (n = 18
      per group and time point). The quality of tendon repair was evaluated based on
      the histological grading score, collagen fiber orientation, gene expression, and
      biomechanical properties. RESULTS: In surgically repaired samples, Doxy enhanced
      the quality of tendon repair compared with no Doxy ( P = .0014). Doxy had a
      significant effect on collagen fiber dispersion, but not principal fiber angle.
      There was a significant effect of time on the gene expression of MMP-3, MMP-9 and
      TIMP1, and Doxy significantly decreased MMP-3 expression at 9 weeks. Doxy
      treatment with surgical repair increased the dynamic modulus at 6 weeks but not
      at 9 weeks after the injury ( P < .001). Doxy also increased the equilibrium
      modulus and decreased creep strain irrespective of the repair group. Doxy did not
      have a significant effect on the histology or biomechanics of unrepaired tendons.
      CONCLUSION: The findings indicate that daily oral administration of Doxy
      accelerated matrix remodeling and the dynamic and equilibrium biomechanics of
      surgically repaired Achilles tendons, although such enhancements were most
      evident at the 3- to 6-week time points. CLINICAL RELEVANCE: The inhibition of
      MMPs at the optimal stage of the repair process may accelerate Achilles tendon
      repair and improve biomechanical properties, especially when paired with surgical
      management.

PMID- 28759733
TI  - Protective effect of rimonabant, a canabinoid receptor 1 antagonist, on
      nonalcoholic fatty liver disease in a rat model through modulation of the hepatic
      expression of activin A and follistatin.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and
      mortality, and there is still no proven effective therapy. The endocannabinoid
      system plays an important role in various liver diseases. Activin A is a member
      of the transforming growth factor beta (TGF-beta) superfamily and inhibits
      hepatocyte growth. Follistatin antagonizes the biological actions of activin A.
      This study was designed to investigate the effect of rimonabant (a potent
      cannabinoid receptor1 (CB1) antagonist) on NAFLD induced with a choline-deficient
      (CD) diet in rats, as well as to detect whether it can alter the hepatic
      expression of activin A and follistatin. Forty rats were distributed among 4
      groups: the control group, the rimonabant treatment group (normal rats that
      received rimonabant); the CD diet group (NAFLD induced with a CD diet); and the
      CD diet + rimonabant group (NAFLD treated with rimonabant). It was found that the
      CD diet caused significant increase in liver index, serum levels of liver
      enzymes, malondialdehyde (MDA), TGF-beta1, activin A, and CB1 expression in liver
      tissue, with a significant decrease in glutathione peroxidase (GSH-Px) and
      follistatin mRNA expression in liver tissues. The administration of rimonabant
      significantly improved all of the studied parameters compared with the group fed
      the CD diet alone. Histopathological examination supported these results. We
      concluded that rimonabant significantly counteracted NAFLD induced with the CD
      diet by decreasing oxidative stress and hepatic expression of TGF-beta1, and
      modulating the hepatic expression of activin A and follistatin.

PMID- 28759734
TI  - The effect of dairy and nondairy beverages consumed with high glycemic cereal on
      subjective appetite, food intake, and postprandial glycemia in young adults.
AB  - The objective was to compare the effect of dairy and nondairy beverages when
      consumed with carbohydrate at breakfast on subjective appetite, food intake (FI),
      and postprandial glycemia (PPG) in healthy young adults. Twenty-six healthy males
      and females (13 males and 13 females; 23.0 +/- 2.6 years; BMI: 22.3 +/- 1.5
      kg/m2) participated in a randomized crossover study. They consumed nonisocaloric
      amounts (250 mL) of almond beverage, soy beverage, 1% fat milk, yogurt beverage,
      and water (control) with cereal and 120 min later, an ad libitum meal. Subjective
      appetite, PPG, and insulin were measured at baseline and at intervals before and
      after the meal at which FI was measured. Post-treatment blood glucose was lowest
      following soy beverage compared with all treatments but was not different from
      milk (p = 0.0002). There were no differences between any other treatments.
      However, over the first hour, PPG for all treatments was 27% lower compared with
      water (p < 0.0001). Milk and yogurt beverage led to the highest insulin
      concentrations post-treatment (p < 0.0001) but there were no differences between
      treatments postmeal. All treatments reduced appetite and led to lower FI at the
      meal compared with water, but FI was lower after milk compared with all
      treatments except yogurt beverage (p < 0.0001). Both dairy and nondairy beverages
      consumed with a high glycemic cereal at breakfast increased satiety and decreased
      FI compared with water with cereal. Despite higher carbohydrate content, all
      beverages led to similar or lower PPG than the water breakfast, but dairy
      beverages increased insulin more than nondairy beverages.

PMID- 28759735
TI  - The effect of dairy products consumed with high glycemic carbohydrate on
      subjective appetite, food intake, and postprandial glycemia in older adults.
AB  - The objective was to compare the effect of liquid, semi-solid, and solid dairy
      products and a nondairy beverage when consumed with glycemic carbohydrate on
      subjective appetite, food intake (FI), and post-prandial glycemia (PPG) in
      healthy older adults. Thirty healthy men and women (14 males and 16 females; age:
      64.6 +/- 2.4 y; BMI: 25.6 +/- 2.5 kg/m2) participated in a randomized crossover
      study. Treatments were one of 250 mL of 2% fat milk and soy beverage, 175 g of 2%
      Greek yogurt, and 30 g of Cheddar cheese consumed as part of an isocaloric (380
      kcal) meal with bread and jam. Water alone served as the energy-free control for
      subjective appetite. At 180 min after consumption, the participants were fed an
      ad libitum meal to measure FI. Subjective appetite, blood glucose, and insulin
      were measured at baseline and at intervals both before (post-treatment) and after
      the meal (postmeal). Cheese and yogurt resulted in lower post-treatment blood
      glucose than milk and soy beverage when consumed with carbohydrate (p < 0.0001),
      but no differences among any treatments were observed postmeal. Treatments led to
      similar insulin concentrations. Post-treatment appetite was lower than after the
      water control for all treatments but suppressed more by cheese and yogurt
      compared with milk (p < 0.0001). There were no differences in FI among
      treatments. Cheese and yogurt increase satiety and lower PPG more than milk or a
      soy beverage when consumed with carbohydrate.

PMID- 28759736
TI  - Phylloplane bacteria of Jatropha curcas: diversity, metabolic characteristics,
      and growth-promoting attributes towards vigor of maize seedling.
AB  - The complex role of phylloplane microorganisms is less understood than that of
      rhizospheric microorganisms in lieu of their pivotal role in plant's
      sustainability. This experiment aims to study the diversity of the culturable
      phylloplane bacteria of Jatropha curcas and evaluate their growth-promoting
      activities towards maize seedling vigor. Heterotrophic bacteria were isolated
      from the phylloplane of J. curcas and their 16S rRNA genes were sequenced.
      Sequences of the 16S rRNA gene were very similar to those of species belonging to
      the classes Bacillales (50%), Gammaproteobacteria (21.8%), Betaproteobacteria
      (15.6%), and Alphaproteobacteria (12.5%). The phylloplane bacteria preferred to
      utilize alcohol rather than monosaccharides and polysaccharides as a carbon
      source. Isolates exhibited ACC (1-aminocyclopropane-1-carboxylic acid) deaminase,
      phosphatase, potassium solubilization, and indole acetic acid (IAA) production
      activities. The phosphate-solubilizing capacity (mg of PO4 solubilized by 108
      cells) varied from 0.04 to 0.21. The IAA production potential (MUg IAA produced
      by 108 cells in 48 h) of the isolates varied from 0.41 to 9.29. Inoculation of
      the isolates to maize seed significantly increased shoot and root lengths of
      maize seedlings. A linear regression model of the plant-growth-promoting
      activities significantly correlated (p < 0.01) with the growth parameters.
      Similarly, a correspondence analysis categorized ACC deaminase and IAA production
      as the major factors contributing 41% and 13.8% variation, respectively, to the
      growth of maize seedlings.

PMID- 28759738
TI  - ABCB1 3435C>T and 2677G>T/A polymorphisms in Polish and Bosnian patients with
      Crohn's disease - A preliminary report.
AB  - The role of ABCB1 single nucleotide polymorphisms (SNPs) in the development of
      Crohn's disease (CD) remains unclear. Due to inconsistent results of several
      European population-based studies and limited information on populations from
      Poland and Bosnia and Herzegovina (B&H), we conducted a preliminary association
      study of two main ABCB1 SNPs and CD. ABCB1 3435C>T and 2677G>T/A SNPs were
      analyzed in Polish and Bosnian patients with CD (n = 85 and n = 30, respectively)
      and controls (n = 82 and n = 30, respectively) using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) for 3435C>T and allele
      specific PCR for 2677G>A/T SNP. A deviation from Hardy-Weinberg equilibrium was
      found for both SNPs in Polish patients with CD, and for 2677G>A/T in Polish
      control group. The allele and genotype frequencies of the two ABCB1 SNPs were not
      significantly different between the CD patients and controls in both populations
      (p > 0.05). Similarly, the genotype distribution of 3435C>T and 2677G>T/A SNPs
      was not significantly different between Polish and Bosnian patients with CD (p >
      0.05). At least one mutated ABCB1 allele was carried by 97.7% of Polish and 90.0%
      of Bosnian patients with CD. No association was found between the ABCB1 SNPs and
      CD in the two populations. In conclusion, the two ABCB1 SNPs may not contribute
      to CD susceptibility in the populations of Poland and B&H. Further studies with
      larger samples in both populations are warranted.

PMID- 28759737
TI  - Differential diagnosis of hepatopulmonary syndrome (HPS): Portopulmonary
      hypertension (PPH) and hereditary hemorrhagic telangiectasia (HHT).
AB  - Hepatopulmonary syndrome (HPS) is a severe complication of advanced liver disease
      associated with an extremely poor prognosis. HPS is diagnosed in 4-47% of
      patients with cirrhosis and in 15-20% of candidates for liver transplantation. In
      addition, severe hypoxia is associated with a high risk of complications of liver
      transplantation (a 30% chance during the first 90 days) and increases the gap
      between transplantation and improving arterial oxygenation. The pathogenesis of
      HPS is not fully understood, and no effective pharmacological treatment has been
      developed yet. Currently, the treatment of choice for HPS is orthotopic liver
      transplantation. Non-specific clinical criteria and the lack of standardized
      diagnostic criteria for determining HPS can lead to diagnostic errors.
      Portopulmonary hypertension and hereditary hemorrhagic telangiectasia, also known
      as Osler-Weber-Rendu syndrome, are pulmonary complications of liver disease which
      should be differentially diagnosed from HPS.

PMID- 28759739
TI  - Online Embryology teaching using learning management systems appears to be a
      successful additional learning tool among Egyptian medical students.
AB  - Although the traditional didactic lecture is considered to be efficient for
      presenting information and providing explanations, it usually does not provide
      adequate time for deeper learning activities. So, traditional lecture is one of
      the most widely criticized educational methods. Virtual learning environment
      (VLE) is a specially designed environment that facilitates teachers' management
      of educational courses for their students, using computer hardware and software,
      which involves distance learning. In this study, we evaluated the experiment of
      online teaching of General Embryology for Egyptian undergraduate medical students
      using WizIQ learning management system. A total of 100 students were invited to
      submit an online survey at the end of the course to evaluate delivery of
      instruction, creation of an environment that supported learning, and
      administrative issues. Most of the students reported that they were strongly
      satisfied with the efficacy of the instructional methods and were strongly
      satisfied with the degree of clarity of the course material. They strongly
      accepted the page format and design of the virtual classroom and strongly agreed
      that the learning environment supported the learning procedure. The item of easy
      logging into the virtual classroom had aberrant variable responses; it recorded
      the lowest mean response; this variation in responses was due to technical
      factors as the students used different devices with different speeds of internet
      connections. Ninety percent of students have strongly recommended the course
      attendance for their fellow students. These results demonstrate that online
      Anatomy teaching using learning management systems appears to be a successful
      additional learning tool among Egyptian medical students.

PMID- 28759740
TI  - Radiological evaluation of maxillary sinus anatomy: A cross-sectional study of
      300 patients.
AB  - OBJECTIVE: The aim of the present study was to evaluate the principal anatomical
      characteristics of the maxillary sinus using Cone Beam Computed Tomography (CBCT)
      in order to facilitate prevention of intra- and post-operative complications.
      MATERIALS AND METHODS: Three hundred CBCT scans from patients undergoing implant
      surgery were analysed. The following anatomical structures were evaluated: (1)
      Residual ridge height (RRH) and width (RRW); (2) Ridge bone density (BD); (3)
      Maxillary sinus angle (MSA); (4) Maxillary sinus lateral wall thickness (LWT);
      (5) Schneiderian membrane thickness (MT); (6) Maxillary sinus septa (SS); (7)
      Posterior superior alveolar artery (PSAA).' RESULTS: Mean patient age was 59.5+/
      13.6. Mean RRH at upper second premolar (2PM) was 8.66+/-3.95mm, 4.90+/-2.28mm at
      first molar (1M), and 5.26+/-2.13mm at second molar (2M). Mean RRW was 6.72+/
      2.69mm at 2PM, 6.87+/-2.65mm at 1M and 7.09+/-2.80mm at 2M. Bone density was
      330.93+/-211.02 Hounsfield Units (HU) at first molar position and MSA was 73.39+/
      15.23 degrees . LWT was 1.95+/-0.98mm. Mean Schneider Membrane thickness (MT) was
      1.82+/-1.59mm; MT was <=3mm in 72.9% of patients and >3mm in 27.10%. 20.56% of
      patients presented bucco-palatal oriented septa with a mean height of 13.11+/
      3.82mm. PSAA was observed in 48.60% and mean distance to the top of the ridge was
      13.15+/-3.71mm, and was mostly observed inside the sinus (53.85%). CONCLUSIONS:
      CBCT scanning has been shown to be a useful tool for evaluating maxillary sinus
      anatomical variations. CBCT should be considered the gold standard when
      evaluating the maxillary sinus area.

PMID- 28759741
TI  - Correction of environmental magnetic fields for the acquisition of Nuclear
      magnetic relaxation dispersion profiles below Earth's field.
AB  - T1 relaxation times can be measured at a range of magnetic field strengths by
      Fast Field-Cycling (FFC) NMR relaxometry to provide T1-dispersion curves. These
      are valuable tools for the investigation of material properties as they provide
      information about molecular dynamics non-invasively. However, accessing
      information at fields below 230 MUT (10kHz proton Larmor frequency) requires
      careful correction of unwanted environmental magnetic fields. In this work a
      novel method is proposed that compensates for the environmental fields on a FFC
      NMR relaxometer and extends the acquisition of Nuclear Magnetic Relaxation
      Dispersion profiles to 2.3MUT (extremely low field region), with direct
      application in the study of slow molecular motions. Our method is an improvement
      of an existing technique, reported by Anoardo and Ferrante in 2003, which
      exploits the non-adiabatic behaviour of the magnetisation in rapidly-varying
      magnetic fields and makes use of the oscillation of the signal amplitude to
      estimate the field strength. This increases the accuracy in measuring the
      environmental fields and allows predicting the optimal correction values by
      applying simple equations to fit the data acquired. Validation of the method is
      performed by comparisons with well-known dispersion curves obtained from polymers
      and benzene.

PMID- 28759742
TI  - 14GHz longitudinally detected electron spin resonance using microHall sensors.
AB  - In this work we developed a home-made LOngitudinally Detected Electron Spin
      Resonance (LODESR) spectrometer based on a microsize Hall sensor. A coplanar
      waveguide (CPW)-resonator is used to induce microwave-excitation on the sample at
      14GHz. We used InSb cross-shaped Hall devices with active areas of (10MUm*10MUm)
      and (5MUm*5MUm). Signal intensities of the longitudinal magnetization component
      of DPPH and YIG samples of volumes about (10MUm)3 and (5MUm)3, are measured under
      amplitude and frequency modulated microwave magnetic field generated by the CPW
      resonator. At room temperature, 109spins/G?Hz sensitivity is achieved for 0.2mT
      linewidth, a result which is still better than most of inductive detected LODESR
      sensitivities.

PMID- 28759743
TI  - Highly resolved HSQC experiments for the fast and accurate measurement of
      homonuclear and heteronuclear coupling constants.
AB  - A number of J-upscaled NMR experiments are currently available to measure
      coupling constants along the indirect F1 dimension of a 2D spectrum. A major
      drawback is the limited F1 digital resolution that requires long acquisition
      times in order to achieve reasonably accurate measures. Here is shown how high
      levels of F1 digital resolution in a multiple-purpose HSQC experiment can be
      easily achieved by implementing a general J/delta-scaling strategy. In
      particular, a set of new J-resolved HSQC experiments is presented for a faster
      and much more accurate J determination in small molecules. Several options and
      practical aspects are discussed and exemplified by measuring the magnitude and/or
      the sign of several homo- and heteronuclear coupling constants in one shot.

PMID- 28759744
TI  - Declining and fluctuating prevalence values of hearing impairment in 18-year old
      Swedish men during three decades.
AB  - OBJECTIVE: To analyze time trends in prevalence of hearing impairment in almost
      complete birth cohorts of 18-year old Swedish men from 1970s up to 2010. STUDY
      GROUPS: Before 1999, all 18-year old men, in Sweden, were called for a compulsory
      conscription examination. In 1971-1999, the participation rate in audiometry was
      73-95%. After 1999, when exemption from conscription was allowed, the
      participation rate gradually declined to 52% in 2004. Samples with participation
      rates below 50% (2005-2010) were considered non-representative and excluded from
      the analyses. RESULTS: High-frequency hearing impairments (HFHI) 35-40 dB HL and
      >=45 dB HL showed a decreasing trend over the observed period, from a prevalence
      of 2.9% (35-40 dB HL) and 3.8% (>=45 dB HL) respectively in 1971 to 1.4% and 1.1%
      respectively in 2004. HFHI 25-30 dB HL, showed slow variations over time and
      decreased from 8.5% in 1971 to 3.2% in 1981 followed by an increase to 10.4% in
      1992. After that year there was a decrease to 5.2% in 2004. The slow fluctuations
      affected only HFHI 25-30 dB HL, mainly at 6 kHz. The left ear was more affected
      than the right ear. CONCLUSIONS: The most important observation was a decrease of
      HFHI 35-40 dB HL by 52% percent and of HFHI >=45 dB HL by 71% between the years
      1971 and 2004. The prevalence of HFHI 25-30 dB HL in young Swedish males
      fluctuated over a period of 33 years. Possible reasons for these trends and
      variations are discussed.

PMID- 28759745
TI  - Changes of metabolism and functional connectivity in late-onset deafness:
      Evidence from cerebral 18F-FDG-PET.
AB  - Hearing loss is known to impact brain function. The aim of this study was to
      characterize cerebral metabolic Positron Emission Tomography (PET) changes in
      elderly patients fulfilling criteria for cochlear implant and investigate the
      impact of hearing loss on functional connectivity. Statistical Parametric Mapping
      T-scores-maps comparisons of 18F-FDG-PET of 27 elderly patients fulfilling
      criteria for cochlear implant for hearing loss (best-aided speech intelligibility
      lower or equal to 50%) and 27 matched healthy subjects (p < 0.005, corrected for
      volume extent) were performed. Metabolic connectivity was evaluated through
      interregional correlation analysis. Patients were found to have decreased
      metabolism within the right associative auditory cortex, while increased
      metabolism was found in prefrontal areas, pre- and post-central areas, the
      cingulum and the left inferior parietal gyrus. The right associative auditory
      cortex was integrated into a network of increased metabolic connectivity that
      included pre- and post-central areas, the cingulum, the right inferior parietal
      gyrus, as well as the striatum on both sides. Metabolic values of the right
      associative auditory cortex and left inferior parietal gyrus were positively
      correlated with performance on neuropsychological test scores. These findings
      provide further insight into the reorganization of the connectome through sensory
      loss and compensatory mechanisms in elderly patients with severe hearing loss.

PMID- 28759746
TI  - Serum markers as an aid in the diagnosis of pulmonary fungal infections in AIDS
      patients.
AB  - INTRODUCTION: The etiology of pulmonary infections in HIV patients is determined
      by several variables including geographic region and availability of
      antiretroviral therapy. MATERIALS AND METHODS: A cross-sectional prospective
      study was conducted from 2012 to 2016 to evaluate the occurrence of pulmonary
      fungal infection in HIV-patients hospitalized due to pulmonary infections.
      Patients' serums were tested for (1-3)-beta-D-Glugan, galactomannan, and lactate
      dehydrogenase. The association among the variables was analyzed by univariate and
      multivariate regression analysis. RESULTS: 60 patients were included in the
      study. The patients were classified in three groups: Pneumocystis jirovecii
      pneumonia (19 patients), community-acquired pneumonia (18 patients), and other
      infections (23 patients). The overall mortality was 13.3%. The time since
      diagnosis of HIV infection was shorter in the pneumocystosis group (4.94 years;
      p=0.001) than for the other two groups of patients. The multivariate analysis
      showed that higher (1-3)-beta-D-Glucan level (mean: 241pg/mL) and lactate
      dehydrogenase (mean: 762U/L) were associated with the diagnosis of
      pneumocystosis. Pneumocystosis was the aids-defining illness in 11 out of 16
      newly diagnosed HIV-infected patients. CONCLUSION: In the era of antiretroviral
      therapy, PJP was still the most prevalent pulmonary infection and (1-3)-beta-D
      Glucan and lactate dehydrogenase may be suitable markers to help diagnosing
      pneumocystosis in our HIV population.

PMID- 28759747
TI  - Clonal dissemination of vancomycin-resistant Enterococcus faecium ST412 in a
      Brazilian region.
AB  - Vancomycin-resistant Enterococcus faecium (VREfm) has emerged as an important
      global nosocomial pathogen, and this trend is associated with the spread of high
      risk clones. Here, we determined the genetic and phenotypic features of 93 VREfm
      isolates that were obtained from patients in 13 hospitals in Vitoria, Espirito
      Santo, Brazil, during 2012-2013. All the isolates were vancomycin-resistant and
      harbored the vanA gene. Only 6 (6.5%) of the VREfm isolates showed the ability to
      form biofilm. The 93 isolates analyzed belong to a single pulsed-field gel
      electrophoresis lineage and presented six subtypes. MLST genotyping showed that
      all VREfm belonged to ST412 (the high-risk clone, hospital-adapted). The present
      study describes the dissemination of ST412 clone in the local hospitals. The
      clonal spread of these ST412 isolates in the area we analyzed as well as other
      hospitals in southeastern Brazil supports the importance of identifying and
      controlling the presence of these microorganisms in health care-related services.

PMID- 28759748
TI  - DNA damage levels in electronics workers in Southern China: A micro-whole blood
      comet assay.
AB  - We evaluated DNA damage levels of different categories of workers exposed to
      hazards inside electronics factories in Southern China. To find out the most
      dangerous risk factor, a cross-sectional study was conducted on a total of 584
      exposed subjects and 138 controls in an electronics factory in Southern China,
      where the electronics industry is prevalent. The exposed hazards included
      isopropanol (IPO), lead, noise, video display terminals (VDT), lead in a high
      temperature (high-temp) environment, and IPO in a high-temp environment. DNA
      damage detection was performed by the micro-whole blood comet assay using
      peripheral blood. DNA damage levels were estimated by percent tail DNA (%T).
      Linear regression models were used to test DNA damage differences between exposed
      groups and control group with adjustments for potential confounding factors. The
      level of DNA damage was more significant in both lead in a high-temp and IPO in a
      high-temp environment groups than in that of the controls (p<0.05). The
      differences remained significant after stratifying by smoking status (p<0.05).
      There were no significant differences between groups exposed to IPO, lead, noise,
      VDT environment and controls. In conclusion, we identified potential risk factors
      for DNA damage to electronics workers. Special attention should be paid to
      workers exposed to IPO and lead in a high-temp environment.

PMID- 28759749
TI  - Effects of long-term oral administration of methimazole on femur and tibia
      properties in male Wistar rats.
AB  - Physiological concentrations of thyroid hormones are crucial for skeletal growth
      and development, physiological bone turnover and bone homeostasis maintenance.
      Methimazole (1-methyl-2-mercaptoimidazole) is an antithyroid drug used for the
      treatment of the hyperthyroidism in humans and animals. The aim of the study was
      to determine effects of long-term oral methimazole treatment in male Wistar rats
      on biochemical bone metabolism markers, as well as morphological, geometric,
      densitometric and mechanical properties of femur and tibia. Experimental rats
      were subjected to 90-day-long oral treatment with 0.05% water solution of
      methimazole and were kept under identical environmental conditions and received
      the same diet ad libitum as the control group. Serum concentration of osteocalcin
      (OC) and C-terminal telopeptides of type I collagen (CTX-I) was determined. Femur
      and tibia were evaluated using quantitative computed tomography (QCT), peripheral
      QCT (pQCT) and three-point bending test. Final body weight of the experimental
      group was significantly decreased by 30% (P=0.01). Methimazole treatment
      significantly decreased serum OC concentration by 21% (P=0.02) and increased CTX
      I concentration by 17% (P=0.06). Methimazole decreased morphological, geometric
      and densitometric parameters of femur and tibia in rats. Mechanical evaluation of
      bones has shown significantly decreased maximum elastic strength and ultimate
      strength of femur in rats treated with methimazole by 36% and 40% when compared
      to the control group (P<0.05). In conclusion, this study has shown that long-term
      treatment with methimazole inhibits bone formation and accelerates bone
      resorption processes. The observed negative effects of methimazole treatment on
      body weight gain and skeletal properties may be considered as additional possible
      side effects in living organisms to those reported in the previous studies. It
      may be suggested that long-term antithyroid treatment should be combined with
      prevention of the negative effects of methimazole on bone tissue and whole body
      metabolism.

PMID- 28759750
TI  - Neuropharmacological and neuroprotective activities of some metabolites produced
      by cell suspension culture of Waltheria americana Linn.
AB  - Waltheria americana is a plant used in Mexican traditional medicine to treat some
      nervous system disorders. The aims of the present study were to isolate and
      determine the neuropharmacological and neurprotective activities of metabolites
      produced by a cell suspension culture of Waltheria americana. Submerged
      cultivation of W. americana cells provided biomass. A methanol-soluble extract
      (WAsc) was obtained from biomass. WAsc was fractionated yielding the
      chromatographic fractions 4WAsc-H2O and WAsc-CH2Cl2. For the determination of
      anticonvulsant activity in vivo, seizures were induced in mice by
      pentylenetetrazol (PTZ). Neuropharmacological activities (release of gamma amino
      butyric acid (GABA) and neuroprotection) of chromatographic fractions were
      determined by in vitro histological analysis of brain sections of mice post
      mortem. Fraction 4WAsc-H2O (containing saccharides) did not produce neuronal
      damage, neurodegeneration, interstitial tissue edema, astrocytic activation, nor
      cell death. Pretreatment of animals with 4WAsc-H2O and WAsc-CH2Cl2 from W.
      americana cell suspensions induced an increase in: GABA release, seizure latency,
      survival time, neuroprotection, and a decrease in the degree of severity of
      tonic/tonic-clonic convulsions, preventing PTZ-induced death of up to 100% of
      animals of study. Bioactive compounds produced in suspension cell culture of W.
      americana produce neuroprotective and neuropharmacological activities associated
      with the GABAergic neurotransmission system.

PMID- 28759751
TI  - Rac2 deficiency attenuates CCl4-induced liver injury through suppressing
      inflammation and oxidative stress.
AB  - Oxidative stress is a leading cause to liver injury. Rac2 is a Ras-associated
      guanosine triphosphatase, an important molecule modulating a large number of
      cells and involved in the regulation of reactive oxygen species (ROS). For the
      study described here, we supposed that Rac2 knockout protects mice against CCl4
      induced acute liver injury. We found that Rac2 expressed highly in CCl4-induced
      liver tissues. CCl4-treated Rac2 knockout (Rac2-/-) mice had reduced CD24 levels
      and steatosis. In addition, CCl4-induced high expression of pro-inflammatory
      cytokines and chemokine were reversed by Rac2 deficiency compared to CCl4-treated
      wild type (WT) mice. We also found that fibrosis-related signals of MMP-9, MMP-2
      and TGF-beta1 were also down-regulated in Rac2 knockout mice induced by CCl4.
      Significantly, oxidative stress induced by CCl4 was also suppressed owing to the
      lack of Rac2, evidenced by enhanced superoxide dismutase (SOD) activity, and
      reduced malondialdehyde (MDA) levels, superoxide radical, H2O2, xanthine oxidase
      (XO), xanthine dehydrogenase (XDH) and XO/XDH ratio. Moreover, c-Jun N-terminal
      protein kinase mitogen-activated protein kinases (JNK MAPK) was activated by
      CCl4, which was reversed in the liver of Rac2-/- mice through western blot and
      immunohistochemical analysis. In vitro, endotoxin (LPS) was treated to
      hepatocytes isolated from WT mice and Rac2-/- mice. The data further confirmed
      the role of Rac2 deficiency suppressed pro-inflammatory cytokines and chemokine,
      as well as fibrosis-related signals. Of note, production of ROS induced by LPS
      was reduced in Rac2-/- cells, accompanied with enhanced SOD1, SOD2 and reduced XO
      and phosphorylated-JNK expressions. Our results indicated that Rac2 played an
      essential role in acute liver injury induced by CCl4, providing the compelling
      information of the effects of Rac2 on liver injury, and revealing a novel
      regulatory mechanism for acute liver injury.

PMID- 28759752
TI  - Efavirenz loaded nanostructured lipid carrier engineered for brain targeting
      through intranasal route: In-vivo pharmacokinetic and toxicity study.
AB  - Intranasal delivery is a potential platform that can be employed in targeting the
      antiretrovirals (ARVs) to reach HIV that harbors in the central nervous system.
      The objective of the study was to develop an optimized efavirenz (EFV) loaded
      nanostructured lipid carrier (ENLC) and deliver it through intranasal route for
      brain targeting. Factorial design (23) was used to identify the key formulation
      variables influencing particle size and percent drug encapsulation of efavirenz
      in the NLC. Optimised ENLC-6 batch exhibited a spherical morphology with a mean
      particle size of 162nm, high drug encapsulation of 95.78+/-0.42% and in-vitro
      drug release of 92.45% at the end of 24h. Single dose in-vivo pharmacokinetic
      studies revealed significant therapeutic concentration of the drug in the CNS
      following IN administration with a Cmax value of 31.45+/-0.75 and T1/2 of 11.14h.
      A 10 fold increase (p<0.001) in% drug targeting efficiency (DTE) and 4.5 fold
      increase (p<0.001) in % drug targeting potential (DTP) for ENLC-6 was observed as
      compared to pure EFV. Sub-acute 28day IN toxicity in experimental animals
      indicated non-toxicity of encapsulated efavirenz over pure drug. Based on the
      findings we conclude that the intelligent choice of the lipdic carrier along with
      the strategic use of excipients can prove helpful for the efficient brain
      targeting of the encapsulated efavirenz which is devoid of toxicity. This may
      prove useful in the management of neuro-AIDS.

PMID- 28759753
TI  - Inhibition of Rad51 sensitizes breast cancer cells with wild-type PTEN to
      olaparib.
AB  - PTEN is a tumor suppressor gene well characterized as a phosphatase. However,
      more evidences demonstrate PTEN functions in DNA repair independent of its
      phosphatase activity, which affects the efficacy of DNA damage anti-tumoral drugs
      in treating cancer cells with PTEN variations. Using BT549 breast cancer cells,
      we studied the roles of PTEN in DNA repair and in sensitization of breast cancer
      cells to olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor. Comet assay
      showed PTEN promoted DNA repair. PTEN-deficient BT549 cells are sensitive to
      olaparib, which shows the synthetic lethality between PTEN and PARP1. We
      expressed PTEN in BT549 cells and found PTEN-proficient BT549 cells resist to
      olaparib. Western blot showed that PTEN up-regulated Rad51 expression, suggesting
      PTEN promotes DNA repair through Rad51-dependnent homologous recombination. We
      used 5MUM olaparib or 5MUM RI-1, a Rad51 inhibitor, to treat PTEN-proficient
      BT549 cells respectively. The immunofluorescent analysis showed the combination
      of olaparib and RI-1 induced more than 4-fold of gammaH2AX foci than either of
      them. MTT assay showed 5MUM RI-1 did not change the survival of PTEN-proficient
      BT549 cells, however, this dose of RI-1 sensitized PTEN-proficient BT549 cells to
      olaparib. Consequently, these results demonstrate that inhibition of Rad51 can
      sensitize BT549 cells with wild type PTEN to olaparib, which would contribute to
      using PARP inhibitors in individual treatment of breast cancer patients with PTEN
      variations.

PMID- 28759754
TI  - Potential of the chlorogenic acid as multitarget agent: Insulin-secretagogue and
      PPAR alpha/gamma dual agonist.
AB  - The chlorogenic acid (CGA) is a natural product isolated from Cecropia
      obtusifolia, which possesses several pharmacological properties, such as: anti
      carcinogenic, neuroprotective, antioxidant, anti-inflammatory, hypoglycemic, and
      hypolipidemic. In relation to its effects on the hyperglycemia and
      hypertriglyceridemia, few is known about the mechanisms in which this compound
      may be acting, therefore, the aim of the present study was to determine if CGA
      acts as an insulin secretagogue increasing intracellular calcium concentrations
      ([Ca2+]i) in RINm5F cells; or as an insulin sensitizer and lipid-lowering agent
      stimulating the expression of PPARgamma and PPARalpha, respectively, in 3T3-L1
      adipocytes. As results, RINm5F cells treated with 200MUM of CGA showed an
      increase in [Ca2+]i of 9-times versus control and 4-times as compared to positive
      control; in addition, an increase in insulin secretion was observed similarly to
      those of positive control. CGA also significantly increased the mRNA expression
      of PPARgamma (150%) and GLUT4 (220%), as well PPARalpha (40%) and FATP (25%) as
      it was appreciated by RT-PCR. Additionally, a chemoinformatic analysis suggested
      that CGA has suitable physicochemical properties to be considered as leader
      bioactive molecule for the development of novel agents with similar properties.
      Together, our results indicate that CGA possesses multiple mechanisms of action
      for the development of highly effective therapeutics in the treatment of
      metabolic diseases such as type 2 diabetes.

PMID- 28759755
TI  - The roles of sodium-glucose cotransporter 2 inhibitors in preventing kidney
      injury in diabetes.
AB  - Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD)
      worldwide. The early effective treatment of high plasma glucose could delay or
      prevent the onset of DN. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are
      new target treatments for ameliorating high plasma glucose and help to maintain
      glucose homeostasis in diabetic patients. Reduced renal glucose reabsorption by
      SGLT2 inhibition seems to have high potential to improve glycemic control in
      diabetes mellitus (DM) not only through glucose lowering but also through glucose
      independent effects such as blood pressure-lowering and direct renal effects in
      diabetes. Of note, the important events in the pathogenesis of glucose-induced
      renal injury and DN including oxidative stress, inflammation, fibrosis and
      apoptosis conditions have shown to be ameliorate after the treatment with SGLT2
      inhibitors. Interestingly, SGLT2 inhibitors have been reported to reduce
      albuminuria in DM via an activation of renal tubuloglomerular feedback by
      increased macula densa sodium and chloride delivery, leading to afferent
      vasoconstriction and attenuated diabetes-induced renal hyperfiltration. These
      effects also help to conserve glomerular integrity. Thus, the treatment of
      diabetes mellitus using SGLT2 inhibitors could be one of the effective approach
      for the management of diabetic-associated kidney disease like DN. This review
      summarizes the up to date information and discusses the bidirectional
      relationship between the SGLT2 inhibitor treatments and the renal functions that
      are available from both basic research and clinical reports. The details of renal
      outcomes of SGLT2 inhibitors in DN are also provide in this review.

PMID- 28759756
TI  - Neuroprotective properties of anthocyanidin glycosides against H2O2-induced glial
      cell death are modulated by their different stability and antioxidant activity in
      vitro.
AB  - The neuroprotective effect of several anthocyanins in combination with their
      stability and antioxidant/pro-oxidant activity has been investigated against H2O2
      induced oxidative stress in C6 glial cells. First it was found that delphinidin
      (Dp) 3-O-glucoside and 3-O-rutinoside were degraded within an hour, and at the
      same time stimulated the production of H2O2 in the micromolar concentration
      range. The stability of peonidin, pelargonidin (Pg), malvidin (Mv) and cyanidin
      (Cy) 3-O-glucosides and Cy 3-O-rutinoside was significantly higher than that of
      Dp 3-O-glycosides, with Pg3G showing the highest percent recovery over time.
      Based on these findings and chemical difference (according to the set of
      functional groups on the B-ring) of tested anthocyanins Cy3G, Mv3G and Pg3G were
      selected as candidates for the protection of glial cells against H2O2-induced
      oxidative stress. It was revealed that Cy3G (5-20MUM) and Mv3G (10-20MUM) but not
      Pg3G protected glial cells against H2O2-induced necrotic cell death. Moreover,
      these anthocyanins sustained the glutathione antioxidant defence system. Finally,
      to the extent of our knowledge we were the first to demonstrate the protective
      effect of Cy3G on the resting mitochondrial respiration rate in H2O2-affected
      glial cells. The results suggest that Cy3G, as the most prominent antioxidant
      among tested anthocyanins, could be a potential adjuvant for the prevention or
      reduction of necrotic glial cell death during the oxidative stress conditions met
      in neurodegenerative diseases. However, further elucidation of other possible
      mechanisms for anthocyanins to protect the nervous system is encouraged.

PMID- 28759757
TI  - Navel orange peel hydroethanolic extract, naringin and naringenin have anti
      diabetic potentials in type 2 diabetic rats.
AB  - The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During
      the last decade, there has been an interest in the expansion of anti-diabetic
      drugs especially those of natural sources. Thus, the aim of this study was to
      assess the anti-hyperglycemic and the anti-hyperlipidemic effects as well as the
      anti-oxidant activities of navel orange hydroethanolic extract and its
      constituting flavonoids naringin and naringenin on nicotineamide
      (NA)/streptozotocin (STZ)-induced type 2 diabetic rats. To induce T2DM, 16h
      fasted rats were intraperitoneally injected with STZ at dose of 50mg/kg body
      weight (b. w.), 15min after the intraperitoneal administration of NA (120mg/kg b.
      w.). The NA/STZ-induced type 2 diabetic rats were orally treated with navel
      orange peel hydroethanolic extract, naringin and narengenin at dose level of
      100mg/kg b. w./day for 4 weeks. The treatments with navel orange peel
      hydroethanolic extract, naringin and narengenin potentially alleviated the
      lowered serum insulin and C-peptide levels, the depleted liver glycogen content,
      the elevated liver glucose-6-phosphatase and glycogen phosphorylase activities,
      the deteriorated serum lipid profile, and the suppressed liver antioxidant
      defense system of NA/STZ-induced type 2 diabetic rats. The treatments also
      enhanced the mRNA expression of insulin receptor beta-subunit, GLUT4 and
      adiponectin in adipose tissue of STZ/NA-induced type 2 diabetic rats. In
      conclusion, the navel orange peel hydroethanolic extract, naringin and naringenin
      have potent anti-diabetic effects in NA/STZ-induced type 2 diabetic rats via
      their insulinotropic effects and insulin improving action which in turn may be
      mediated through enhancing insulin receptor, GLUT4 and adiponectin expression in
      adipose tissue.

PMID- 28759758
TI  - Kiwi fruit (Actinidia deliciosa) ameliorates gentamicin-induced nephrotoxicity in
      albino mice via the activation of Nrf2 and the inhibition of NF-kappaB (Kiwi &
      gentamicin-induced nephrotoxicity).
AB  - Gentamicin is a potent aminoglycoside antibiotic, but the risk of nephrotoxicity
      limits its prolonged use. The toxicity of gentamicin is believed to result from
      oxidative stress, a condition that could be counteracted by dietary antioxidants.
      This study determines the possible renoprotective effects of kiwifruit against
      the pathophysiological and ultrastructural alterations induced by gentamicin.
      Mice were intraperitoneally injected with gentamicin (100mg/kg body weight) for
      eight consecutive days, and kiwi juice was administered for 8days, either
      concomitant to or after gentamicin injection. Gentamicin caused nephrotoxicity
      evidenced by the significant elevation of serum creatinine and blood urea
      nitrogen levels, along with significant reduction of serum sodium and potassium
      ions, compared to normal controls. This was associated with proximal tubular
      necrosis, lysosomal accumulation and mitochondrial alterations, together with
      glomerular atrophy, mesangial hypercellularity, and inflammatory cell
      infiltration. Moreover, immunohistochemical results pointed to the relevant role
      of Nrf2 and NF-kappaB in gentamicin-induced nephrotoxicity. Kiwi administration,
      especially when given after gentamicin injection, significantly ameliorated
      gentamicin-induced pathophysiological alterations, increased the nuclear
      immunoreactivity of Nrf2 and decreased that of NF-kappaB. In short, kiwi fruit
      shows a promising role as a nephroprotective agent against gentamicin-induced
      nephrotoxicity via attenuating oxidative stress, inflammation and cell death.

PMID- 28759759
TI  - Ultrasonic backscatter from elongated grains using line focused ultrasound.
AB  - Ultrasonic backscattering from polycrystalline materials with elongated grains is
      investigated. A normal incident line-focus transducer is employed such that
      refracted longitudinal and transverse waves are focused within the polycrystal
      and scatter at grain boundaries back to the transducer. A ray-based scattering
      model is developed to explain the dependence of the statistics of scattering
      measurements on grain elongation. The spatial variance of measured scattered
      signals from Al alloy (7475-T7) is compared to the model. This work promotes the
      ultrasonic backscatter technique for monitoring grain elongation of metals using
      one transducer with access to a single sample face.

PMID- 28759760
TI  - Should we abandon the APTT for monitoring unfractionated heparin?
AB  - INTRODUCTION: The activated partial thromboplastin time (APTT) is commonly used
      to monitor unfractionated heparin (UFH) but may not accurately measure the amount
      of heparin present. The anti-Xa assay is less susceptible to confounding factors
      and may be a better assay for this purpose. MATERIALS AND METHODS: The validity
      of the APTT for monitoring UFH was assessed by comparing with an anti-Xa assay on
      3543 samples from 475 patients (infants [n=165], children 1-15years [n=60] and
      adults [n=250]) receiving treatment dose UFH. RESULTS: Overall concordance was
      poor. The highest concordance (66%; 168/254) was seen in children. Concordance
      (51.8%) or discordance (48.4%) was almost equal in adult patients. Among adult
      patients whose anti-Xa level was within 0.3-0.7IU/mL, only 38% had an APTT in the
      therapeutic range whilst 56% were below and 6% were above therapeutic range.
      Children and adult patients with anti-Xa of 0.3-0.7IU/mL but sub- therapeutic
      APTT had significantly higher fibrinogen levels compared to those with
      therapeutic or supra-therapeutic APTT. CONCLUSIONS: When the anti-Xa level was
      0.3-0.7IU/mL, the majority of samples from infants demonstrated a supra
      therapeutic APTT, whilst adults tended to have a sub-therapeutic APTT. This may
      lead to under anticoagulation in infants or over anticoagulation in adults with
      risk of bleeding if APTT is used to monitor UFH. These results further strengthen
      existing evidence of the limitation of APTT in monitoring UFH. Discordance of
      APTT and anti-Xa level in adults and children may be due to elevation of
      fibrinogen level.

PMID- 28759761
TI  - Platelet count and plateletcrit are associated with an increased risk of venous
      thrombosis in females. Results from the RETROVE study.

PMID- 28759763
TI  - Trends in biomarkers, biotic indices, and fish population size revealed
      contrasting long-term effects of recycled water on the ecological status of a
      Mediterranean river.
AB  - Recycled water is important for maintaining river flow in semi-arid regions.
      However, it has ecological risk, as suggested by comparison of habitat and white
      and red blood cell count in two wild fish species (Barbus meridionalis and
      Squalius laietanus) before and after an input of recycled water in Ripoll River
      (NE Spain) in 2009. Due to the lack of normal ranges for blood variables in wild
      fish, we surveyed seasonally the same river reaches in 2013 to test if blood
      alterations from 2009 compromised the viability of the fish populations. By
      examining other indicators of river health in baseline and polluted sites (fish
      abundance, mass-length relationships, and community indices in fish, diatoms and
      invertebrates), we tested for the superior utility of blood tests in
      biomonitoring. The comparison of water quality and scores of diatoms and
      invertebrate indices between polluted and reference sites showed that polluted
      sites improved from 2009 to 2013. The abundance of B. meridionalis also increased
      in polluted sites, but that of S. laietanus declined in 2013 compared to 2009.
      These results contrast with results of blood analyses in 2009, which suggested
      that B. meridionalis was more seriously affected by pollution than S. laietanus.
      The fish index did not reveal the risk of recycled water to fish health, whereas
      fish mass-length relationships suggested that S. laietanus individuals in 2013
      had a better body condition in polluted than in reference sites. Given that the
      two fish species had opposite results in reference sites, and that the physical
      habitat was more suitable for B. meridionalis in polluted sites in 2013 than was
      for S. laietanus, trends in population size are not only explained by pollution.
      The role of phenology is suggested by peaks in blood disorders during the
      breeding season. However, more long-term studies combining indicators of river
      health at the individual and community scales are needed to fully assess the
      ecological risk of recycled water in this river. These studies will also help to
      develop blood tests as reliable health indicators in wild fish populations.

PMID- 28759764
TI  - Importance of exposure dynamics of metal-based nano-ZnO, -Cu and -Pb governing
      the metabolic potential of soil bacterial communities.
AB  - Metal-based engineered nanomaterials (ENMs) are known to affect bacterial
      processes and metabolic activities. While testing their negative effects on
      biological components, studies traditionally rely on initial exposure
      concentrations and thereby do not take into consideration the dynamic behavior of
      ENMs that ultimately determines exposure and toxicity (e.g. ion release).
      Moreover, functional responses of soil microbial communities to ENMs exposure can
      be caused by both the particulate forms and the ionic forms, yet their relative
      contributions remain poorly understood. Therefore, we investigated the dynamic
      changes of exposure concentrations of three different types of ENMs (nano-ZnO, 
      Cu and -Pb) and submicron particles (SMPs) in relation to their impact on the
      capacity of soil bacterial communities to utilize carbon substrates. The
      different ENMs were chosen to differ in dissolution potential. The dynamic
      exposures of ENMs were considered using a time weighted average (TWA) approach.
      The joint toxicity of the particulate forms and the ionic forms of ENMs was
      evaluated using a response addition model. Our results showed that the effect
      concentrations of spherical nano-ZnO, -Cu and SMPs, and Pb-based perovskites
      expressed as TWA were lower than expressed as initial concentrations. Both
      particulate forms and ionic forms of spherical 18nm, 43nm nano-ZnO and 50nm,
      100nm nano-Cu contribute to the overall response at the EC50 levels. The
      particulate forms for 150nm, 200nm and 900nm ZnO SMPs and rod-shaped 78nm nano-Cu
      mainly affected the soil microbial metabolic potential, while the Cu ions
      released from spherical 25nm nano-Cu, 500nm Cu SMPs and Pb ions released from
      perovskites mainly described the effects to bacterial communities. Our results
      indicate that the dynamic exposure of ENMs and relative contributions of
      particles and ions require consideration in order to pursue a naturally realistic
      assessment of environmental risks of metal-based ENMs.

PMID- 28759762
TI  - Low-level maternal exposure to nicotine associates with significant metabolic
      perturbations in second-trimester amniotic fluid.
AB  - Decades of public health research have documented that smoking in pregnancy poses
      significant health risks to both mother and child. More recent studies have shown
      that even passive maternal exposure to secondhand smoke associates with negative
      birth outcomes. However, the mechanisms linking exposure to outcomes have
      remained obscure. As a first step toward defining the metabolic consequence of
      low-level nicotine exposure on fetal development, we conducted an untargeted
      metabolomic analysis of 81 paired samples of maternal serum and amniotic fluid
      collected from karyotypically normal pregnancies in the second trimester. By
      comparing the m/z and retention times of our mass spectral features with
      confirmed standards, we identified cotinine, a nicotine derivative, and used the
      calculated cotinine concentrations to classify our maternal serum samples into
      exposure groups using previously defined cut-offs. We found that cotinine levels
      consistent with low-level maternal exposure to nicotine associated with distinct
      metabolic perturbations, particularly in amniotic fluid. In fact, the metabolic
      effects in amniotic fluid of ostensibly low-level exposed mothers showed greater
      overlap with perturbations previously observed in the sera of adult smokers than
      did the perturbations observed in the corresponding maternal sera. Dysregulated
      fetal pathways included aspartate and asparagine metabolism, pyrimidine
      metabolism, and metabolism of other amino acids. We also observed a strong
      negative association between level of maternal serum cotinine and acetylated
      polyamines in the amniotic fluid. Combined, these results confirm that low-level
      maternal nicotine exposure, indicated by a maternal serum cotinine level of 2
      10ng/mL, is associated with striking metabolic consequences in the fetal
      compartment, and that the affected pathways overlap those perturbed in the sera
      of adult smokers.

PMID- 28759765
TI  - Bioaccumulation and toxicity studies of macroalgae (Charophyceae) treated with
      aluminium: Experimental studies in the context of lake restoration.
AB  - The objective of this study was to examine the impact of aluminium on the
      perennial macroalgae Chara hispida L. and its bioaccumulation capacities.
      Aluminium (Al) was introduced into the environment in the form of polyaluminium
      chloride, an agent utilized in the restoration of waterbodies. Research was
      conducted in an experimental setting using mesocosms (volume 0.8m3) placed in the
      littoral zone of a lake with C. hispida. Three doses of the coagulant were
      applied, each with a different volume: low - 6.1g Al m-3, medium - 12.2gm-3 and
      high - 24.5g Al m-3. A significant acidification of environment was determined,
      which would imply the presence of toxic Al3+ ions. It has been demonstrated that
      aluminium penetrates and accumulates in the cells of the charophyte. This caused
      damage to the thalli, which manifested itself in chloroses, necroses, flaking of
      the cortex cells and softening of the thallus, whose severity was proportionate
      to the dose of the coagulant. The first negative signs were observed after 24h.
      The study shows that C. hispida is a poor accumulator of aluminium
      (bioconcentration factor < 200), while bioaccumulation capacity was inhibited at
      the concentration of approx. 2.0mg Al g-1 d.w. Accumulation in the thalli of the
      charophytes accounted for 58% of variation following removal of aluminium from
      the environment. The results of the experiment demonstrate a negative impact of
      aluminium on charophytes at concentrations used in aggressive restoration of
      lakes.

PMID- 28759766
TI  - Metal toxicity assessment by sentinel species of mangroves: In situ case study
      integrating chemical and biomarkers analyses.
AB  - Globally, there is a lack of knowledge about tropical ecotoxicology dealing with
      the potential impact of metal contamination in mangrove ecosystem. This habitat
      is considered a nursery for several animal species, among them the "uca"-crab
      (Ucides cordatus), known as a key species due to its biological and economical
      importance. This study evaluated the association involving metal contamination
      (Cd, Cu, Pb, Cr, Mn and Hg) in water, sediment, red-mangrove vegetation
      (Rhizophora mangle) and tissues of uca crab, together with its geno-cytotoxic
      responses, based on micronucleated hemocytes frequency and the retention time of
      neutral red in lysosomes. We assessed six mangrove areas with distinct pollution
      levels in Sao Paulo State, Brazil, where the water and sediment contamination by
      metals were associated with accumulation of these pollutants in biotic
      compartments (mangrove leaves and crab). In U. cordatus, metal accumulation was
      best explained by metal concentration found in leaves of R. mangle than in the
      water or sediment, indicating that feeding drives metal exposure in this
      organism. Mercury (Hg) concentration in sediment, copper (Cu) concentration in
      hepatopancreas of U. cordatus and lead (Pb) in water and green leaves of R.
      mangle showed a significant correlation with genotoxic impact in U. cordatus.
      However, copper concentration (in green/senescent leaves and hepatopancreas) and
      lead (in sediment), were the major metals affecting lysosomal membrane integrity.
      Therefore, representatives of all compartments were associated with cyto and
      genotoxicity in this species, thus requiring a holistic approach to issues
      related to sublethal damage. Probability estimates of cytogenetic impacts related
      to metal concentration in abiotic compartments (significantly correlated with
      known biomarkers: Hg in sediment; and Pb in water and sediment) are also
      presented. Our results highlight the need for environmental restoration of
      mangroves areas contaminated with metals, responsible for cytogenetic injuries
      and revealing a pre-pathological condition in this sentinel species, in addition
      to ecological disturbances.

PMID- 28759767
TI  - Heavy metals in contaminated environment: Destiny of secondary metabolite
      biosynthesis, oxidative status and phytoextraction in medicinal plants.
AB  - Contamination of soils, water and air with toxic heavy metals by various human
      activities is a crucial environmental problem in both developing and developed
      countries. Heavy metals could be introduced into medicinal plant products through
      contaminated environment (soil, water and air resources) and/or poor production
      practices. Growing of medicinal plants in heavy metal polluted environments may
      eventually affect the biosynthesis of secondary metabolites, causing significant
      changes in the quantity and quality of these compounds. Certain medicinal and
      aromatic plants can absorb and accumulate metal contaminants in the harvestable
      foliage and, therefore, considered to be a feasible alternative for remediation
      of polluted sites without any contamination of essential oils. Plants use
      different strategies and complex arrays of enzymatic and non-enzymatic anti
      oxidative defense systems to cope with overproduction of ROS causes from the
      heavy metals entered their cells through foliar and/or root systems. This review
      summarizes the reports of recent investigations involving heavy metal
      accumulation by medicinal plants and its effects on elicitation of secondary
      metabolites, toxicity and detoxification pathways, international standards
      regarding in plants and plant-based products, and human health risk assessment of
      heavy metals in soil-medicinal plants systems.

PMID- 28759768
TI  - Identification for the capability of Cd-tolerance, accumulation and translocation
      of 96 sorghum genotypes.
AB  - Cadmium (Cd) pollution is a worldwide environmental problem which heavily
      threatens human health and food security. Sorghum, as one of the most promising
      energy crop, has been considered to be the source of high-quality feedstock for
      ethanol fuel. Ninety-six sorghum genotypes were investigated under hydroponic
      conditions to compare their capabilities of Cd-tolerance, accumulation and
      translocation for their potential in remediation of Cd contamination. Different
      genotypes varied largely in the tolerance to Cd stress with tolerance indexes
      ranked from 0.107 to 0.933. Great difference was also found in Cd uptake and
      accumulation with concentrations ranging from 19.0 to 202.4mg/kg in shoots and
      277.0-898.3mg/kg in roots. The total amounts of Cd ranked from 6.1 to 25.8MUg per
      plant and the highest translocation factor was over 4 times higher than the
      lowest one. The correlation analysis demonstrated that Cd concentration in shoot
      reflected the ability of Cd translocation and tolerance of sorghum, and the path
      coefficient analysis indicated that root biomass could be taken as a biomarker to
      evaluate Cd extraction ability of sorghum. The results in this study can
      facilitate the restoring of Cd contaminated areas by sorghum.

PMID- 28759769
TI  - Changes in illicit, licit and stimulant designer drug use patterns in South-East
      Hungary between 2008 and 2015.
AB  - The aim of this work is to present the changes in classical illicit and licit
      drug, as well as stimulant designer drug (SDD) consumption of suspected drug
      users in South-East Hungary between 2008 and 2015. Urine and/or blood samples of
      2976 subjects were analyzed for these groups of substances of which 1777 (59.7%)
      were tested positive. THC was the most frequent (32.2%) substance, followed by
      classical stimulants (amphetamine, metamphetamine, MDMA, cocain) (21.4%), SDDs
      (17.0%), benzodiazepines (15.5%), medical opiates (codeine without morphine,
      methadone, tramadol) (4.03%), and morphine with or without 6-acethyl-morphine
      (1.98%). The annual rate of cannabis consumption continuously decreased after
      2010. The use of classical stimulants was constant, except for a significant
      increase in 2015. Benzodiazepine incidence increased and remained steady after
      2011. Medical opiate and morphine frequency was variable. SDDs were found in the
      highest number in 2012-13, exceeding the frequency of classical stimulants. The
      most prevalent SDDs were as follows: 2010 - mephedrone, 2011 - 4-MEC, methylone,
      MDPV, 4-FMC, and 4-FA, and 2012-2015 - pentedrone. Beside pentedrone, 3-MMC,
      alphaPVP, alphaPHP, and 4-CMC were detected with a notable number in this period.
      Multi-drug use was found in 30-43% of suspects tested positive between 2008 and
      2014, which elevated to 52% in 2015. The frequency of substances in the
      biological samples corresponded to their seizure rate. When SDDs were included on
      the NPS list, their frequency in biological samples and in seized materials
      slightly decreased or did not change. However, a marked decrease was observed
      following classification as illicit drugs.

PMID- 28759770
TI  - Downward dog becomes fit body, inc.: A content analysis of 40 years of female
      cover images of Yoga Journal.
AB  - The present analysis investigated temporal trends in physical appearance
      attributes and attire worn by female cover models of Yoga Journal magazine
      between the years 1975-2015. Covers featuring a single female model (N=168) were
      coded for: pose activity, amount of body visibility, perceived body size, body
      shape, breast size, skin exposure, and revealing or form-fitting attire. When
      collapsed across all decades, the majority of cover models was actively posed
      with high body visibility, rated as at most low normal weight, possessed either a
      "thin/lean" or "skinny/boney" body shape, and were "flat-chested" or "small
      breasted". Greater body visibility, pose activity, thinness/leanness, skin
      exposure, and form-fitting attire were featured on more recent years' covers.
      Findings suggest that the female "yoga body" conforms to the contemporary thin-
      and-toned media fitness ideal, particularly recently, which may promote
      objectified body competence, an unhealthy drive for leanness, and dissuade higher
      weight women from considering yoga practice.

PMID- 28759771
TI  - Body appreciation, interest in cosmetic enhancements, and need for uniqueness
      among U.S. college students.
AB  - The aim of the current study was to examine associations between body
      appreciation and putative correlates that focus on self-enhancement and self
      expression. Students (N=261; mean age=20.16years, SD=3.68; 60.9% female) from a
      non-residential college in the northeastern United States completed a
      questionnaire measuring body appreciation, interest in cosmetic enhancements, and
      need for uniqueness. Individuals with higher body appreciation and African
      Americans/Blacks reported significantly higher self-attributed need for
      uniqueness and significantly higher investment in a distinctive appearance. The
      association between body appreciation and interest in cosmetic enhancements
      (e.g., hair coloring) was not significant. Results suggest that body appreciation
      may be linked to a desire to express one's own unique qualities.

PMID- 28759772
TI  - Maternal HIV infection associated with reduced transplacental transfer of measles
      antibodies and increased susceptibility to disease.
AB  - BACKGROUND: Transplacental transfer of measles antibodies from mother to fetus is
      important in protecting against measles during early infancy. Changes in
      population immunity against measles in adults, including waning of immunity among
      HIV-infected pregnant women, could affect passive immunity acquired in utero by
      newborns. OBJECTIVES: To evaluate the effect of maternal HIV infection on
      transplacental transfer of measles antibody in mother-newborn dyads in a setting
      of high maternal HIV prevalence. STUDY DESIGN: Serum at birth was obtained from
      303 mother-newborn dyads, including 196 HIV-infected and 107 HIV-uninfected
      women, and tested for measles IgG antibodies by ELISA. Seronegativity was defined
      as antibody levels <150mIU/ml and seroprotective titers as >=330mIU/ml. RESULTS:
      HIV-infected and -uninfected women had similar measles antibody titers, however,
      cord-blood titers were lower among HIV-exposed (788.06mIU/ml) compared to HIV-
      unexposed newborns (1306.6mIU/ml; p<=0.001), due to lower transplacental antibody
      transfer ratio in HIV-exposed (0.63) than in HIV-unexposed newborns (0.97;
      p<=0.001). Maternal age <25years of age was associated with lower antibody titers
      and lower percentage with seroprotective titer, as well as less likelihood of
      their newborns having seroprotective titers (70.2% vs. 86.5%; p=0.001).
      CONCLUSIONS: Lower levels of measles antibody in HIV-exposed newborns and in
      younger women <25years old, increases the susceptibility of their newborns to
      developing measles. This suggest a need to re-evaluate measles immunization of
      women of child bearing age and the timing of measles vaccination among infants in
      settings with a high prevalence of maternal HIV-infection.

PMID- 28759774
TI  - A waterborne outbreak involving hepatitis A virus genotype IA at a residential
      facility in the Republic of Korea in 2015.
AB  - BACKGROUND: Hepatitis A virus (HAV), a major cause of acute hepatitis, has had
      the highest occurrence among group 1 nationally notifiable infectious diseases in
      Korea since 2010.Recently,the annual increase in the HAV infection rate among
      young adults has become a public health concern. OBJECTIVES: The aim of this
      study was to describe an outbreak of acute hepatitis in a residential facility in
      April 2015 and to identify potential sources of this outbreak. STUDY DESIGN: Sera
      from all exposed residents were tested for anti-HAV IgM or IgG antibodies by
      ELISA. Clinical (sera and stool) and environmental samples were screened for the
      presence of HAV RNA using one-step RT-PCR and nested PCR. The VP3-VP1 regions of
      HAV were analyzed using the BLAST database and MEGA7 software. RESULTS: Of the 82
      persons in the facility, 12 (14.6%, including 10 residents and 2 health care
      workers) were diagnosed with hepatitis A. Clinical symptoms were evident in 9
      individuals, one of whom died, and the remaining four patients were asymptomatic.
      Traceback investigation revealed that HAV-RNA (genotype IA) was detected in the
      patients' stools and the groundwater used in the facility. CONCLUSIONS: We
      described an HAV outbreak in a facility for the disabled due to using a water
      supply that was mixed with contaminated groundwater. Therefore, HAV vaccination
      and periodic water inspections in group facilities should be emphasized to
      prevent HAV infection.

PMID- 28759773
TI  - High incidence of maternal parvovirus B19 infection in a large unselected
      population-based pregnancy cohort in Norway.
AB  - BACKGROUND: Around 40% of pregnant women in Norway are parvovirus B19 (B19V)
      seronegative and thus at risk for B19 V infection. Studies on samples from women
      with symptomatic disease or known exposure have shown that nucleic acid
      amplification assays combined with serology increase the sensitivity and improves
      the diagnostic procedure. OBJECTIVES: The aim was to investigate the
      seroprevalence of B19V infection, the occurrence of new infections and vertical
      transmission in a population-based pregnancy cohort, with special emphasis on the
      diagnostic methods. STUDY DESIGN: We randomly selected 1350 pregnant women from
      the Norwegian Mother and Child Cohort Study (MoBa), using an algorithm for the
      detection of B19V infection, including both serology and PCR. RESULTS: Maternal
      infection was confirmed in 50 subjects (3.7% of 1349 women), of which 35(70%)
      were viremic. Of the initially seronegative 33(6.8%) seroconverted. The estimated
      average annual seroconversion rate was 15.5%, with the highest estimated annual
      seroconversion rate of 31.6%. The rates of yearly seroconversion followed the
      pattern found in reports from Norwegian microbiology laboratories. Among all
      women, 31 (2.3%) had an inconclusive serological profile and 17 (54.8%) had
      detectable virus. Of the 16 women with virus detectable at gestational week 17
      18, seven were still seronegative with absent seroconversion in the second sample
      taken at birth. All together 10 children were vertically infected. CONCLUSIONS:
      High incidence of viremic B19V infections and high estimated annual
      seroconversion rates were found. Lack of seroconversion despite longstanding
      viremia emphasizes the importance of including PCR when testing for B19V
      infection during pregnancy.

PMID- 28759775
TI  - Forensic mental health evaluations of military personnel with traumatic life
      event, in a university hospital in Ankara, Turkey.
AB  - INTRODUCTION: The definition of psychological trauma has been rephrased with the
      DSM-5. From now on, witnessing someone else's traumatic event is also accepted as
      a traumatic life event. Therefore, the psychiatric examination of forensic cases
      gains importance for not overlooking a psychiatric trauma. This research aims to
      discuss the psychiatric examinations of military personnel who had a traumatic
      life event and to reveal psychiatric states of soldiers after trauma. MATERIALS
      AND METHODS: The forensic reports prepared at Gulhane Military Medical Academy
      (GMMA), Forensic Medicine polyclinic between January 1, 2011 and November 30,
      2014 were examined, and among them the cases sent to GMMA Psychiatry polyclinic
      for psychiatric examination were analyzed retrospectively. RESULTS: There were a
      total of 2408 cases who applied for the arrangement of a judicial report and 167
      of them required a psychological examination. Among 167 cases, 165 were male and
      2 were female, and the mean age was 25.6 years. Anxiety disorder (53.9%) was the
      most common diagnosis as a result of the psychiatric examination, following
      posttraumatic stress disorder (PTSD) (18.6%), and 3.6% had no psychopathology. It
      was determined that injuries caused by firearms (38.3%) and explosive materials
      (26.3%) had caused psychological trauma the most. On the other hand, 11 (6.6%)
      cases were determined to have undergone a psychological trauma on account of
      being a witness to their friends' injuries during the conflict without
      experiencing any physical injury. There were not any statistically significant
      relationships between the severity of physical injury and being PTSD or anxiety
      disorder. DISCUSSION: Development of PTSD risk is directly correlated with the
      nature of trauma. The trauma types of the cases in our study were in the high
      risk group because of the military population. Our study is of importance in
      terms of putting forward the psychiatric disorders seen in the military
      population with traumatic life history associated with war (combat-related). In
      this research, 26.1% of the cases followed up due to combat-related trauma were
      diagnosed with PTSD. Interestingly, this ratio was lower than the studies that
      have larger case numbers. There is still the need to conduct studies that will
      involve larger participants.

PMID- 28759776
TI  - Fatal poisoning by butane sniffing: A forensic analysis and immunohistochemical
      detection of myocardial hypoxic damage.
AB  - Although less widespread than twenty years ago, inhalant abuse remains an on
      going problem, whose incidence among U.S. teenagers and young adults ranges from
      10 to 15%. Death due to the inhalation of vapor from halogenated hydrocarbons is
      a well-known phenomenon, yet few cases of fatal butane-gas poisoning have been
      described. Many cases of volatile substance abuse in prison populations have been
      reported: drug-addicted inmates often resort to this alternative practice when
      unable to get their habitual drugs of abuse. A similar pattern occurs especially
      among adolescents. The study herein described was conducted including all cases
      of fatal acute intoxication of butane gas examined from 2007 to 2015 at the
      Institute of Legal Medicine and Forensic Sciences of the University of Genoa. In
      the absence of overt and specific macroscopic and histological findings
      indicating cause and pathological mechanism of death, we aimed to assess whether
      recent cardiac lesions were detectable by way of immunohistochemical (IHC)
      analysis. Specifically, fibronectin and troponin C expression in myocardial
      tissues were investigated in deaths from acute butane-gas poisoning so as to
      better define the underlying pathological mechanisms. IHC findings were
      indicative of hypoxic cardiac damage. In all cases, positivity to fibronectin and
      mildly to moderately reduced troponin C expression in cardiac muscle cells were
      immunohistochemically ascertained.

PMID- 28759777
TI  - Color stability of dental restorative materials submitted to cold temperatures
      for forensic purposes.
AB  - In the post-mortem examination of the dental arches of accident victims in cold
      locations, dental restorative materials can be found. Cold temperatures can be
      capable of causing color changes of aesthetic materials, such as composite resin
      (CR) and glass ionomer cement (GIC). The aim of this study was to evaluate the
      effect of the cold action on the color stability of CR and GIC restorations, in
      order to discriminate them and enable the adequate comparison between antemortem
      and post-mortem data. Sixty bovine teeth (30 CR and 30 GIC) were prepared (6 * 6
      * 2 mm) and separated into groups (n = 10). The color readouts were taken by a
      portable spectrophotometer, before and after of cold action (2.5  degrees C, -20 
      degrees C, -80  degrees C) inside of freezers. There were color alterations in
      the coordinates (DeltaE, DeltaL*, Deltaa* e Deltab*) for both materials. The
      authors concluded that cold was capable of producing changes in color in the two
      esthetic materials, with similar intensities between the two, at all the
      temperatures studied, when analyzed at 7 days. After being submitted to cold for
      30 days, the changes were more significant for CR, allowing it to be
      differentiated from GIC after 30 days, at all the temperatures tested. Therefore,
      the test proposed in the study was shown to be practical, feasible and capable of
      helping Forensic Odontology with the identification of victims.

PMID- 28759778
TI  - The perils of aiming too high: Discrepancy between goals and performance in
      individuals with depressive symptoms.
AB  - BACKGROUND AND OBJECTIVES: Negative evaluation processes play a pivotal role in
      the development and maintenance of depressive symptoms. However, it remains to be
      understood, whether evaluation processes in depression are impaired by
      maladaptive goal setting. METHOD: In a non-clinical sample (N = 50) of
      individuals with high (BDI-II-Score: 13-29) and low (BDI-II-Score: 0-3) levels of
      depressive symptoms goal setting prior to working on a cognitive task was
      measured. Goal feasibility was experimentally manipulated using an easy and a
      difficult version of the task. RESULTS: When goal feasibility was low, a high
      level of depressive symptoms was associated with setting unattainable goals.
      Whereas individuals with low level of depressive symptoms adjusted their goals to
      a lower (more realistic) level when task difficulty increased, individuals with
      high level of depressive symptoms initially adhered to significantly higher
      goals, so that their performance failed to meet their self-set standards. After
      depressed individual revised their goals downwards, their subsequent performance
      on the task also worsened. LIMITATIONS: The use of a non-clinical sample with
      self-reported depressive symptoms limits the generalizability of our findings to
      a clinical population. Future research would benefit from the use of a larger
      sample with patients suffering from clinical depression. CONCLUSIONS: The
      findings support the notion that negative evaluation processes in depressed
      individuals might be linked with their tendency to generate intractable conflicts
      between self-set inappropriate high goals and their own capacities to perform.
      However, the findings need to be confirmed in clinical samples to draw
      conclusions about the role of goal setting in negative evaluation processes in
      depression.

PMID- 28759780
TI  - Neural correlates of evaluating self and close-other in physical, academic and
      prosocial domains.
AB  - Behavioral studies showed that self-concept can be distinguished into different
      domains, but few neuroimaging studies have investigated either domain-specific or
      valence-specific activity. Here, we investigated whether evaluating self- and
      mother-traits in three domains (physical, academic, prosocial) relies on similar
      or distinct brain regions. Additionally, we explored the topical discussion in
      the literature on whether vmPFC activity during self-evaluations is induced by
      valence or importance of traits. Participants evaluated themselves and their
      mothers on positive and negative traits in three domains. Across all domains,
      evaluating traits resulted in right dlPFC, left middle temporal cortex, bilateral
      thalamus, and right insula activity. For physical traits, we found specific
      neural activity in brain regions typically implicated in mentalizing (dmPFC,
      IPL). For academic traits, we found a brain region typically implicated in
      autobiographical memories (PCC), and for prosocial traits, social brain regions
      (temporal pole, TPJ) were activated. Importantly, these patterns were found for
      both self and mother evaluations. Regarding valence, rACC/vmPFC showed stronger
      activation for positive than for negative traits. Interestingly, activation in
      this region was stronger for highly important traits compared to low/neutral
      important traits. Thus, this study shows that distinct neural processes are
      activated for evaluating positive and negative traits in different domains.

PMID- 28759779
TI  - Synthetic lethality between murine DNA repair factors XLF and DNA-PKcs is rescued
      by inactivation of Ku70.
AB  - DNA double-strand breaks (DSBs) are recognized and repaired by the Classical Non
      Homologous End-Joining (C-NHEJ) and Homologous Recombination pathways. C-NHEJ
      includes the core Ku70 and Ku80 (or Ku86) heterodimer that binds DSBs and thus
      promotes recruitment of accessory downstream NHEJ factors XLF, PAXX, DNA-PKcs,
      Artemis and other core subunits, XRCC4 and DNA Ligase 4 (Lig4). In the absence of
      core C-NHEJ factors, DNA repair can be performed by Alternative End-Joining,
      which likely depends on DNA Ligase 1 and DNA Ligase 3. Genetic inactivation of C
      NHEJ factors, such as Ku70, Ku80, XLF, PAXX and DNA-PKcs results in viable mice
      showing increased levels of genomic instability and sensitivity to DSBs.
      Knockouts of XRCC4 or Lig4, on the other hand, as well as combined inactivation
      of XLF and DNA-PKcs, or XLF and PAXX, result in late embryonic lethality in mice,
      which in most cases correlate with severe apoptosis in the central nervous
      system. Here, we demonstrate that inactivation of the Ku70 gene rescues the
      synthetic lethality between XLF and DNA-PKcs, resulting in triple knockout mice
      that are indistinguishable from Ku70-deficient littermates by size or levels of
      genomic instability. Moreover, we find that combined inactivation of Ku70 and XLF
      results in viable mice. Together, these findings suggest that Ku70 is epistatic
      with XLF and DNA-PKcs and support a model in which inactivation of Ku70 allows
      DNA lesions to become accessible to alternative DNA repair pathways.

PMID- 28759781
TI  - Metabolic changes sustain the plant life in low-sulfur environments.
AB  - Plants assimilate inorganic sulfate into various organic sulfur (S) compounds,
      which contributes to the global sulfur cycle in the environment as well as the
      nutritional supply of this essential element to animals. Plants, to sustain their
      lives, adapt the flow of their S metabolism to respond to external S status by
      activating S assimilation and catabolism of stored S compounds, and by repressing
      the synthesis of secondary S metabolites like glucosinolates. The molecular
      mechanism of this response has been gradually revealed, including the discovery
      of several regulatory proteins and enzymes involved in S deficiency responses.
      Recent progress in this research area and the remaining issues are reviewed here.

PMID- 28759782
TI  - Intergenerational associations in executive function between mothers and children
      in the context of risk.
AB  - Executive functioning (EF) is critical for school readiness and other important
      life skills. Previous investigations have often neglected the important influence
      of parental EF skills in shaping their own children's EF. This study attempted to
      replicate recent empirical work that has shown that maternal EF is positively
      related to child EF. An ecological theoretical framework was used to examine the
      maternal EF-child EF link in family environments characterized by significant
      risk and socioeconomic adversity. Data from 38 mother-child dyads revealed that
      larger maternal working memory capacity was associated with greater child
      accuracy and slower reaction times on a child-friendly Go/No-Go task of response
      inhibition but not on an Emotional Go/No-Go task. This finding suggests that in
      contexts of risk and adversity, slower reaction times, instead of reflecting
      weaker EF skills, might reflect an adaptive skill-that is, exercising appropriate
      caution and careful responding on a challenging task. Results provide additional
      evidence of an intergenerational link between maternal EF and child EF and yield
      new insights into the nature of EF in adverse environments.

PMID- 28759783
TI  - Association of polybrominated diphenylethers (PBDEs) and hydroxylated metabolites
      (OH-PBDEs) serum levels with thyroid function in thyroid cancer patients.
AB  - Polybrominated diphenylethers (PBDE) have been demonstrated to be associated with
      significant alterations in hormone levels in humans. However, yet few
      epidemiological human evidence has associated thyroid function with hydroxylated
      polybrominated diphenylethers (OH-PBDEs), which may be more potent in disrupting
      thyroid hormone homeostasis. In the present study, the body burdens of 7 PBDEs
      and 11 OH-PBDEs as well as the serum thyroid status were examined in a cohort of
      33 thyroid cancer patients. The levels of ?PBDEs and ?OH-PBDEs ranged from 1.07
      to 39ng/g lipid, and 0.01-0.46ng/g lipid, respectively. BDE-47, 6-OH-BDE-47 and 3
      OH-BDE-47 were the predominant congeners. The associations between these PBDE
      congeners and thyroid function were not significant after controlling for
      sociodemographic characteristics, as well as the associations between OH-PBDEs
      and free T3. There were an inverse association between lg3-OH-BDE-47 and lgFT4
      (free T4) but a positive association between lg4'-OH-BDE-49 and TSH. Both
      lgSigma5OH-PBDEs (the sum of HO-tetra-BDEs) and lgSigmaOH-PBDEs were
      significantly and positively associated with lgTSH. Our results are consistent
      with most human studies, suggesting that OH-PBDEs can alter thyroid function by
      enhancing the elimination of serum FT4 with elevated TSH levels. To our
      knowledge, this is the first study to examine and report associations between OH
      PBDEs and thyroid function in a cancer population.

PMID- 28759784
TI  - Development of a model for particulate matter pollution in Australia with
      implications for other satellite-based models.
AB  - Estimating exposure to particulate matter (PM10) air pollution concentrations in
      Australia is challenging due to relatively few monitoring sites relative to the
      geographic distribution of the population. We modelled daily ground-level PM10
      concentrations for the period 2006-2011 for Australia using linear mixed models
      with satellite remote-sensed AOD, land-use and geographical variables as
      predictors. The variation in daily PM10 explained by the model was 51% for
      Australia overall, and ranged from 51% for Tasmania to 78% for South Australia.
      Cross-validation indicated that the models were most suitable for prediction in
      New South Wales and Victoria and least suitable for prediction in Western
      Australia, the Australian Capital Territory and Tasmania. Most of the variation
      in PM10 concentrations was explained by temporal rather than spatial variation.
      The inclusion of AOD and other predictors did not substantially improve model
      performance. Temporal models were sufficient to account for daily PM10 variation
      recorded by statutory monitors.

PMID- 28759785
TI  - In vitro cleavage of bioactive peptides by peptidases from Bothrops jararaca
      venom and its neutralization by bothropic antivenom produced by Butantan
      Institute: Major contribution of serine peptidases.
AB  - In Brazil, envenomation by Bothrops pitvipers is responsible for over 73% of
      snakebites, and their venom is a rich source of proteolytic enzymes. Most studies
      have demonstrated that Bothrops jararaca venom acts on macromolecular substrates,
      causing an imbalance in the victim's hemostatic system. In contrast, fewer
      studies have examined the proteolytic activity on small molecules such as
      peptides. In this study, we used a set of bioactive peptides (insulin B chain,
      Met-enkephalin, Leu-enkephalin, neuropeptide Y, peptide YY, pancreatic
      polypeptide, substance P and somatostatin) to identify new peptide substrates for
      the metallopeptidases and serine peptidases from the B. jararaca venom. The
      majority of these peptides were substrates for the venom, but neuropeptide Y and
      pancreatic polypeptide presented higher hydrolyses rates. Although most of the
      peptides were simultaneously substrates for both classes of proteases, serine
      peptidases were the most active. Substance P was an exclusive substrate for
      metallopeptidases, while somatostatin was a selective substrate for serine
      peptidases. The neutralizing efficacy of the bothropic antivenom produced by the
      Butantan Institute was also assessed and found to totally prevent substance P
      hydrolysis, whereas somatostatin cleavage was not inhibited. Thus, the antivenom
      effectively inhibited metallopeptidase activity, but did not neutralize some of
      the serine peptidases. These results indicate that, in addition to cleaving
      proteins, the proteolytic enzymes from this venom also hydrolyze bioactive
      peptides, and this peptidase activity could effectively contribute to some of the
      many dire manifestations of envenomation.

PMID- 28759786
TI  - High purity tocotrienols attenuate atherosclerotic lesion formation in apoE-KO
      mice.
AB  - Previous studies have demonstrated that tocotrienol (T3) has antiatherogenic
      effects. However, the T3 preparations used in those studies contained
      considerable amounts of tocopherol (Toc), which might affect the biological
      activity of T3. There is little information on the effect of highly purified T3
      on atherosclerosis formation. This study investigated the effect of high-purity
      T3 on atherosclerotic lesion formation and the underlying mechanisms. Male
      apolipoprotein E knockout (apoE-KO) mice were fed a cholesterol-containing diet
      either alone or supplemented with T3 concentrate (Toc-free T3) or with alpha-Toc
      for 12 weeks. ApoE-KO mice fed the 0.2% T3-supplemented diet showed reduced
      atherosclerotic lesion formation in the aortic root. The 0.2% T3 diet induced
      Slc27a1 and Ldlr gene expression levels in the liver, whereas the alpha-Toc
      supplemented diet did not affect those expression levels. T3 was predominantly
      deposited in fat tissue in the T3 diet-fed mice, whereas alpha-Toc was
      preferentially accumulated in liver in the alpha-Toc diet-fed mice. Considered
      together, these data demonstrate that dietary T3 exerts anti-atherosclerotic
      effect in apoE-KO mice. The characteristic tissue distribution and biological
      effects of T3, that are substantially different from those of Toc, may contribute
      to the antiatherogenic properties of T3.

PMID- 28759787
TI  - Ferulic acid, a bioactive component of rice bran, improves oxidative stress and
      mitochondrial biogenesis and dynamics in mice and in human mononuclear cells.
AB  - The aim of the study was to characterize the vascular effects of rice bran
      enzymatic extract (RBEE). ApoE-/- mice were fed a high-fat/cholesterol diet (HFD)
      or HFD supplemented with 5% RBEE for 21 weeks. RBEE prevented development of
      atherosclerotic plaques and oxidative stress in mouse aorta as well as the down
      regulation of markers of mitochondrial biogenesis. Analysis of the bioactive
      components identified ferulic acid (FA) as responsible component. In healthy
      human volunteers, FA intake reduced NADPH oxidase activity, superoxide release,
      apoptosis and necrosis in peripheral blood mononuclear cells. Differentiation and
      proliferation of endothelial progenitor cells were improved. In summary, the
      study identifies FA as a major active component of rice bran, which improves
      expression of mitochondrial biogenesis and dynamics markers and reduces oxidative
      stress in a mouse model of vascular damage as well as in endothelial cells and
      human mononuclear cells.

PMID- 28759788
TI  - Isolation of vanadium-resistance endophytic bacterium PRE01 from Pteris vittata
      in stone coal smelting district and characterization for potential use in
      phytoremediation.
AB  - This study investigates the V-resistant endophytic bacteria isolated from V
      accumulator Pteris vittata grown on stone coal smelting district. Among all the
      ten isolates, the strain PRE01 identified as Serratia marcescens ss marcescens by
      Biolog GEN III MicroPlateTM was screened out by ranking first in terms of heavy
      metal resistance and plant growth promoting traits. The S. marcescens PRE01 had
      strong V, Cr and Cd resistance especially for V up to 1500mg/L. In addition, it
      exhibited ACC deaminase activity, siderophore production and high indoleacetic
      acid production (60.14mg/L) and solubilizing P potential (336.41mg/L). For heavy
      metal detoxification tests, PRE01 could specifically assimilate 97.6%, 21.7% and
      6.6% of Cd(II), Cr(VI) and V(V) within 72h incubation. Despite the poor
      absorption of the two anions, most V(V) and Cr(VI) were detoxified and reduced to
      lower valence states by the strain. Furthermore, the isolate had the potential to
      facilitate the metals uptake of their hosts by changing heavy metal speciation.
      Our research may open up further scope of utilizing the endophyte for enhancing
      phytoextraction of vanadium industry contaminated soils.

PMID- 28759789
TI  - Changes in carbohydrate levels and relative water content (RWC) to distinguish
      dormancy phases in sweet cherry.
AB  - Perennial trees require chilling, i.e. a period of cold temperature in the
      winter, for flowering next spring; sweet cherry is particularly prone to lack of
      chilling. The objective of this study is to identify possible transition points
      to clearly distinguish dormancy phases by relating carbohydrate and relative
      water content (RWC) in reproductive buds to concomitant chilling fulfilment. This
      contribution proposes the use of four transition points between the dormancy
      phases and their characterization in terms of carbohydrates, water contents in
      combination with chilling values and may allow upscaling to other dormancy
      studies in trees; two groups of cherry varieties were defined based on their
      different initial sorbitol and starch level in the autumn. The first separation
      between para- and (deep) d-endo-dormancy is characterized as a transition from a
      decrease (variety group 1) or a constant level (variety group 2) to a sharp
      increase in hexoses and sorbitol and a drop of starch content. The second
      transition point (d-endo- to f-endo-dormancy) is characterized as the changes in
      both hexoses (increase) and starch (decrease) terminate and ca. 650 Chilling
      Hours (CH), i.e. insufficient chilling in the concomitant forcing experiment with
      cut branches. This third transition point (f-endo- to eco-dormancy) was
      characterized by ca. 1000 CH, the minimum chilling requirement and restrained
      flowering (cut branches). The fourth transition point (forcing initiation) marked
      an increase in water content at ca. 1550 CH, optimum chilling for cherry and
      coincided with natural flowering. A ratio of hexoses (glucose plus fructose) to
      starch content (<2:1) appeared to be a potential indicator of the beginning of
      chilling (para-dormancy) and a ratio of 14-20:1 typical for endo-dormancy,
      whereas the release from dormancy was associated with a decline to less than 10:1
      at the end of winter (eco-dormancy). To our knowledge, this is the first time
      that transition points are identified based on constituents (carbohydrates and
      relative water content) in floral buds related to current chilling status and
      dormancy phases and are also presented in a schematic diagram. The understanding
      of these changes in relative water content and carbohydrate levels may contribute
      to manage insufficient chilling in the orchard and support climate change studies
      with trees.

PMID- 28759790
TI  - Roscotanes and roscoranes: Oxygenated abietane and pimarane diterpenoids from
      Kaempferia roscoeana.
AB  - Eight previously undescribed ditepenoids, including four oxygenated abietanes
      (roscotanes A-D) and four oxygenated pimaranes (roscoranes A-D), along with
      twelve known diterpenoids were isolated from the whole plants of Kaempferia
      roscoeana. Their structures were elucidated by extensive spectroscopic analysis,
      and the structure of roscotane A was further confirmed by single crystal X-ray
      diffraction analysis. Most isolated compounds were evaluated for their
      antimicrobial and antimalarial activities.

PMID- 28759791
TI  - Problematic internet use among high school students: Prevalence, associated
      factors and gender differences.
AB  - This study aimed to measure the prevalence of Problematic Internet Use (PIU)
      among high school students and to identify factors associated with PIU
      underlining gender differences. The students filled a self-administered,
      anonymous questionnaire collecting information on demographic characteristics and
      patterns of Internet use. Multiple logistic regression analysis was performed to
      identify factors associated with PIU in the overall sample and by gender. Twenty
      five schools and 2022 students participated in the survey. Prevalence of PIU was
      14.2% among males and 10.1% among females. Males 15-year-olds and females 14-year
      olds had the highest PIU prevalence that progressively lowered with age among
      females. Only 13.5% of pupils declared parents controlled their Internet use. The
      sensation of feeling lonely, the frequency of use, the number of hours of
      connection, and visiting pornographic websites were associated with the risk of
      PIU in both genders. Attending vocational schools, the activities of chatting and
      file downloading, and the location of use at Internet point among males, and
      younger age among females were associated with PIU, whilst information searching
      was protective among females. PIU could become a public health problem in the
      next years. The physical and mental health consequences should be studied.

PMID- 28759792
TI  - Dual starch-polyacrylamide polymer system for improved flocculation.
AB  - Organic polyelectrolytes such as polyacrylamide (PAM) are commonly used in the
      water industry to improve flocculation. However, potential adverse health effects
      may arise from the use of PAM owing to the presence of trace acrylamide monomers
      in commercial products. Hence, there is growing interest in replacing synthetic
      polyelectrolytes with natural and sustainable alternatives, which would eliminate
      risks related to the presence of toxic monomers/impurities and oxidation by
      products from the interaction of polymers and common disinfectants such chlorine
      and ozone. Starch-based flocculants are recognized to offer fairly good
      flocculation performance, but require higher polymer dosages than conventional
      high-molecular-weight PAM. To reduce exposure to acrylamide monomers, this study
      examined the combination of an activated starch-based polymer with PAM to
      determine whether synergistic effects can be achieved using a dual polymer
      system. Flocculation performance (floc size, density and rate of aggregation) was
      monitored using jar tests. Turbidity removal was also assessed to confirm
      settling performance. Single PAM/starch mixture injection and sequential dual
      polymer injection were compared in order to simplify practical industrial
      applications. For the tested samples of surface water and wastewater, jar tests
      showed that the PAM dosage can be significantly reduced (50-70% for surface
      water) for both conventional and ballasted flocculation if a dual starch-PAM
      polymer system is used.

PMID- 28759793
TI  - Modelling recovery of ammonium from urine by electro-concentration in a 3-chamber
      cell.
AB  - Electro-concentration enables treatment and nutrient recovery from source
      separated urine, and is a potential technology for on-site treatment using a 3
      compartment configuration that has anode, cathode and middle concentrate
      compartments. There is a particular focus on driving concentration towards the
      precipitation threshold in the concentrate compartment to generate solid ammonium
      salts, including ammonium bicarbonate. To evaluate controlling mechanisms and the
      feasibility of achieving high concentrations, a dynamic mechanistic model was
      developed and validated using experiments with synthetic urine. It was identified
      that high concentrations are prevented by increased back diffusion (diffusion
      from the middle chamber to the anolyte and catholyte) due to large concentration
      gradients, and the preferential migration of protons or hydroxide ions due to a
      loss of buffering capacity in the anolyte and catholyte (due to pH extremes).
      Model-based sensitivity analysis also identified that electrolyte ion
      concentrations (including buffer capacity) were the main controlling mechanisms,
      rather than membrane or electrolyte current transfer capacity. To attain high
      concentrations, operation should be done using a) a high current density (however
      there is a maximum efficient current density); b) feed at short hydraulic
      retention time to ensure sufficient buffer capacity; and c) a feed high in
      ammonium and carbonate, not diluted, and not contaminated with other salts, such
      as pure ureolysed urine. Taking into account electron supply and bio-anodic
      buffer limitations, model testing shows at least double the aqueous
      concentrations observed in the experiments may be achieved by optimising simple
      process and operational parameters such as flow rate, current density and feed
      solution composition. Removal of total ammonium nitrogen (TAN) and total
      carbonate carbon (TCC) was between 43-57% and 39-53%, respectively. Balancing the
      sometimes conflicting process goals of high concentrations and removal percentage
      will need to be considered in further application. Future experimental work
      should be directed towards developing electrodes capable of higher current
      densities. In addition it would be desirable to use ion exchange membranes with
      higher resistance to water fluxes and which limit back diffusion. Future
      modelling work should describe osmotic and electro-osmotic water fluxes as a
      function of the concentration gradient across the membranes and ionic fluxes,
      respectively. More generalised wastewater physico-chemistry speciation models
      should identify best methods where relatively simple Davies activity corrections
      do not apply.

PMID- 28759794
TI  - Iodinated trihalomethane formation during chloramination of iodate-containing
      waters in the presence of zero valent iron.
AB  - Iodide (I-) and iodinated X-ray contrast media (ICM) are the primary iodine
      sources for the formation of iodinated disinfection byproducts (I-DBPs), and
      iodate (IO3-) is believed to be a desired sink of iodine in water. This study
      found that highly cytotoxic iodinated trihalomethanes (I-THMs) also can be
      generated from iodate-containing waters (without any other iodine sources) in the
      presence of zero valent iron (ZVI) during chloramination, which could be a big
      issue in the wide usage of iron pipes. The effect of major factors including ZVI
      dosage, NH2Cl and IO3- concentrations, initial pH, Br-/IO3- molar ratio,
      phosphate concentration, iron corrosion scales (goethite and hematite) on the
      formation of I-THMs were investigated. Formation of I-THMs from IO3- increased
      with the increase of ZVI dosage, IO3- and NH2Cl concentrations. Chloramines can
      also remarkably accelerate the reduction of IO3- by ZVI. Peak I-THM formation was
      found at pH 8. As the Br-/IO3- molar ratio increased from 0 to 20, I-THM
      formation considerably enhanced, especially for the bromine-incorporated species.
      Goethite and hematite enhanced the formation of I-THMs in the presence of ZVI.
      Additionally, a significant suppression on I-THM formation was observed with the
      addition of phosphate. Considering that a large number of water distribution
      networks contain unlined cast iron pipes, transformation of IO3- in the presence
      of ZVI during chloramination may contribute to the formation of I-THMs in such
      systems.

PMID- 28759795
TI  - Effect of engineered environment on microbial community structure in biofilter
      and biofilm on reverse osmosis membrane.
AB  - Four dual media filters (DMFs) were operated in a biofiltration mode with
      different engineered environments (DMF I and II: coagulation with/without
      acidification and DMF III and IV: without/with chlorination). Designed biofilm
      enrichment reactors (BERs) containing the removable reverse osmosis (RO) coupons,
      were connected at the end of the DMFs in parallel to analyze the biofilm on the
      RO membrane by DMF effluents. Filtration performances were evaluated in terms of
      dissolved organic carbon (DOC) and assimilable organic carbon (AOC). Organic
      foulants on the RO membrane were also quantified and fractionized. The bacterial
      community structures in liquid (seawater and effluent) and biofilm (DMF and RO)
      samples were analyzed using 454-pyrosequencing. The DMF IV fed with the
      chlorinated seawater demonstrated the highest reductions of DOC including LMW-N
      as well as AOC among the other DMFs. The DMF IV was also effective in reducing
      organic foulants on the RO membrane surface. The bacterial community structure
      was grouped according to the sample phase (i.e., liquid and biofilm samples),
      sampling location (i.e., DMF and RO samples), and chlorination (chlorinated and
      non-chlorinated samples). In particular, the biofilm community in the DMF IV
      differed from the other DMF treatments, suggesting that chlorination exerted as
      stronger selective pressure than pH adjustment or coagulation on the biofilm
      community. In the DMF IV, several chemoorganotrophic chlorine-resistant biofilm
      forming bacteria such as Hyphomonas, Erythrobacter, and Sphingomonas were
      predominant, and they may enhance organic carbon degradation efficiency. Diverse
      halophilic or halotolerant organic degraders were also found in other DMFs (i.e.,
      DMF I, II, and III). Various kinds of dominant biofilm-forming bacteria were also
      investigated in RO membrane samples; the results provided possible candidates
      that cause biofouling when DMF process is applied as the pretreatment option for
      the RO process.

PMID- 28759796
TI  - Inhibition of Salmonella by thyme essential oil and its effect on microbiological
      and sensory properties of minced pork meat packaged under vacuum and modified
      atmosphere.
AB  - The antibacterial activity of thyme essential oil (TEO) was evaluated against
      four serovars of Salmonella (S. Enteritidis, S. Typhimurium, S. Montevideo and S.
      Infantis), experimentally inoculated (106CFU/g) in minced pork, which was treated
      with different concentrations of the TEO (0.3%, 0.6% and 0.9%) packaged under
      vacuum or MAP (30%O2/50%CO2/20% N2) and stored at 3+/-1 degrees C for 15days. GC
      MS analysis of the TEO was performed in order to determine composition, and the
      predominant constituent was thymol (50.48%), followed by p-cymene and linalool.
      The minimum inhibitory concentration was determined for each Salmonella serovar
      studied. Among the tested active compounds, thymol and carvacrol exhibited the
      greatest inhibitory effect followed by TEO, with minimum inhibitory
      concentrations of 320 to 640MUg/ml. S. Enteritidis was the most sensitive
      serovar. During the storage period, Salmonella counts in pork were reduced by
      1.69-4.05logCFU/g. The influence of TEO on Enterobacteriaceae, lactic acid
      bacteria and total viable count was determined in control mince with no added
      Salmonella. The most pronounced antibacterial effect was achieved by the
      combination MAP and 0.9% TEO. Although the antibacterial activities of all
      studied concentrations of TEO in pork were evident and significant (P<0.05),
      sensory analysis showed that 0.3% TEO was the most acceptable to trained
      panellists.

PMID- 28759797
TI  - Survival of selected foodborne pathogens on dry cured pork loins.
AB  - The safety of ready-to-eat products such as cured pork loins must be guaranteed
      by the food industry. In the present study, the efficacy of the dry curing
      process of pork loins obtained from free-range pigs in the reduction of three of
      the most important foodborne pathogens is analysed. A total of 28 pork loin
      segments, with an average weight of 0.57+/-0.12kg, were divided into four groups
      with three being inoculated by immersion with 7logCFU/ml of either Salmonella
      Typhimurium, Campylobacter coli or Listeria innocua and the last one inoculated
      by immersion with sterile medium (control group). The loin segments were treated
      with a seasoning mixture of curing agents and spices, packed in a synthetic
      sausage casing and cured for 64days. Microbiological analysis, pH and water
      activity (aw) were assessed at four stages. The values of pH and aw decreased
      with curing time as expected. S. Typhimurium and C. coli dropped significantly
      (3.28 and 2.14 log units, respectively), but limited reduction of L. innocua
      (0.84 log unit) was observed along the curing process. In our study, three
      factors were considered critical: the initial concentration of the bacteria, the
      progressive reduction of pH and the reduction of aw values. Our results encourage
      performing periodic analysis at different stages of the manufacturing of dry
      cured pork loins to ensure the absence of the three evaluated foodborne
      pathogens.

PMID- 28759798
TI  - Bacterial species and mycotoxin contamination associated with locust bean, melon
      and their fermented products in south-western Nigeria.
AB  - The microbiological safety of spontaneously fermented foods is not always
      guaranteed due to the undefined fermenting microbial consortium and processing
      materials. In this study, two commonly consumed traditional condiments (iru and
      ogiri) and their respective raw seeds (locust bean and melon) purchased from
      markets in south-western Nigeria were assessed for bacterial diversity and
      mycotoxin contamination using 16S rRNA gene sequencing and liquid chromatography
      tandem mass spectrometry (LC-MS/MS), respectively. Two hundred isolates obtained
      from the raw seeds and condiments clustered into 10 operational taxonomic units
      (OTUs) and spanned 3 phyla, 10 genera, 14 species and 2 sub-species. Bacillus
      (25%) and Staphylococcus (23.5%) dominated other genera. Potentially pathogenic
      species such as Alcaligenes faecalis, Bacillus anthracis, Proteus mirabilis and
      Staphylococcus sciuri subsp. sciuri occurred in the samples, suggesting poor
      hygienic practice during production and/or handling of the condiments. A total of
      48 microbial metabolites including 7 mycotoxins [3-nitropropionic acid, aflatoxin
      B1 (AFB1), AFB2, beauvericin, citrinin, ochratoxin A and sterigmatocystin] were
      quantified in the food samples. Melon and ogiri had detectable aflatoxin levels
      whereas locust bean and iru did not; the overall mycotoxin levels in the food
      samples were low. There is a need to educate processors/vendors of these
      condiments on good hygienic and processing practices.

PMID- 28759799
TI  - Quantitative and qualitative analysis of regulatory T cells in B cell chronic
      lymphocytic leukemia.
AB  - Accumulated data indicate a significant role of T cell dysfunction in the
      pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are
      significantly higher and show lower apoptotic levels compared to healthy donors.
      We demonstrate that CLL derived CD4+CD25-CD127- and CD4+CD25lowCD127-
      subpopulations share a common immunophenotypic profile with conventional Tregs
      and are associated with advanced stage disease. We further provide evidence that
      the increased number of Tregs contributes indirectly to the proliferation of the
      CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL
      cells. These data are further supported by our observations that CLL derived
      Tregs appear rather incapable of inducing apoptosis of both normal B cells and
      CLL cells, in contrast to normal Tregs, suggesting an immunoediting effect of CLL
      cells on Tregs which negatively affects the functionality of the latter and
      contributes to the failure of Tregs in CLL to efficiently eliminate the abnormal
      clone.

PMID- 28759800
TI  - Mesenchymal stem cells derived from multiple myeloma patients protect against
      chemotherapy through autophagy-dependent activation of NF-kappaB signaling.
AB  - Chemotherapy resistance has been considered as a major problem for multiple
      myeloma (MM) treatment and bone marrow microenvironment plays a crucial role in
      the MM progression and chemoresistance. Recent studies reported that bone marrow
      mesenchymal stem cells derived from MM patients (MM-MSCs) revealed various
      characteristics compared with these from healthy subjects (NM-MSCs). However, the
      functions and mechanisms by which MM-MSCs mediate the chemotherapy resistance of
      MM remain unclear. In this study, we show that MM-MSCs decreased melphalan or
      doxorubicin-induced cell cycle arrest and apoptosis in two MM cell lines (U266
      and RPMI-8226). Mechanistically, we demonstrate that MM-MSCs promote the
      expressions of autophagy related genes to activate autophagy, followed by
      ultimately NF-kappaB signaling activation in MM cells. Inhibition of NF-kappaB
      signaling reversed the protective effects of MM-MSC on MM cells. Moreover,
      autophagy inhibitor chloroquine (CQ) or 3-Methyladenine (3MA) treatment
      significantly suppressed phosphorylation and consequently degradation of NF
      kappaB inhibitor I-kappaBalpha, reduced MM-MSCs-mediate activation of NF-kappaB
      and prevented MM-MSCs-induced resistance. Taken together, our findings indicate
      MM-MSCs are involved in the mechanism of the chemotherapy resistance of MM.
      Therefore, the inhibition of MM-MSCs-induced autophagy may combat chemotherapy
      resistance and provide a promising therapeutic strategy for MM treatment.

PMID- 28759801
TI  - Assignment of solid-state 13C and 1H NMR spectra of paramagnetic Ni(II)
      acetylacetonate complexes aided by first-principles computations.
AB  - Recent advances in computational methodology allowed for first-principles
      calculations of the nuclear shielding tensor for a series of paramagnetic
      nickel(II) acetylacetonate complexes, [Ni(acac)2L2] with L = H2O, D2O, NH3, ND3,
      and PMe2Ph have provided detailed insight into the origin of the paramagnetic
      contributions to the total shift tensor. This was employed for the assignment of
      the solid-state 1,2H and 13C MAS NMR spectra of these compounds. The two major
      contributions to the isotropic shifts are by orbital (diamagnetic-like) and
      contact mechanism. The orbital shielding, contact, as well as dipolar terms all
      contribute to the anisotropic component. The calculations suggest reassignment of
      the 13C methyl and carbonyl resonances in the acac ligand [Inorg. Chem.53, 2014,
      399] leading to isotropic paramagnetic shifts of delta(13C) ~ 800-1100 ppm and
      ~180-300 ppm for 13C for the methyl and carbonyl carbons located three and two
      bonds away from the paramagnetic Ni(II) ion, respectively. Assignment using three
      different empirical correlations, i.e., paramagnetic shifts, shift anisotropy,
      and relaxation (T1) were ambiguous, however the latter two support the
      computational results. Thus, solid-state NMR spectroscopy in combination with
      modern quantum-chemical calculations of paramagnetic shifts constitutes a
      promising tool for structural investigations of metal complexes and materials.

PMID- 28759802
TI  - Color vision predicts processing modes of goal activation during action
      cascading.
AB  - One of the most important functions of cognitive control is action cascading: the
      ability to cope with multiple response options when confronted with various task
      goals. A recent study implicates a key role for dopamine (DA) in this process,
      suggesting higher D1 efficiency shifts the action cascading strategy toward a
      more serial processing mode, whereas higher D2 efficiency promotes a shift in the
      opposite direction by inducing a more parallel processing mode (Stock, Arning,
      Epplen, & Beste, 2014). Given that DA is found in high concentration in the
      retina and modulation of retinal DA release displays characteristics of D2
      receptors (Peters, Schweibold, Przuntek, & Muller, 2000), color vision
      discrimination might serve as an index of D2 efficiency. We used color
      discrimination, assessed with the Lanthony Desaturated Panel D-15 test, to
      predict individual differences (N = 85) in a stop-change paradigm that provides a
      well-established measure of action cascading. In this task it is possible to
      calculate an individual slope value for each participant that estimates the
      degree of overlap in task goal activation. When the stopping process of a
      previous task goal has not finished at the time the change process toward a new
      task goal is initiated (parallel processing), the slope value becomes steeper. In
      case of less overlap (more serial processing), the slope value becomes flatter.
      As expected, participants showing better color vision were more prone to activate
      goals in a parallel manner as indicated by a steeper slope. Our findings suggest
      that color vision might represent a predictor of D2 efficiency and the
      predisposed processing mode of goal activation during action cascading.

PMID- 28759803
TI  - No evidential value in samples of transcranial direct current stimulation (tDCS)
      studies of cognition and working memory in healthy populations.
AB  - A substantial number of studies have been published over the last decade,
      claiming that transcranial direct current stimulation (tDCS) can influence
      performance on cognitive tasks. However, there is some skepticism regarding the
      efficacy of tDCS, and evidence from meta-analyses are mixed. One major weakness
      of these meta-analyses is that they only examine outcomes in published studies.
      Given biases towards publishing positive results in the scientific literature,
      there may be a substantial "file-drawer" of unpublished negative results in the
      tDCS literature. Furthermore, multiple researcher degrees of freedom can also
      inflate published p-values. Recently, Simonsohn, Nelson and Simmons (2014)
      created a novel meta-analytic tool that examines the distribution of significant
      p-values in a literature, and compares it to expected distributions with
      different effect sizes. Using this tool, one can assess whether the selected
      studies have evidential value. Therefore, we examined a random selection of
      studies that used tDCS to alter performance on cognitive tasks, and tDCS studies
      on working memory in a recently published meta-analysis (Mancuso et al., 2016).
      Using a p-curve analysis, we found no evidence that the tDCS studies had
      evidential value (33% power or greater), with the estimate of statistical power
      of these studies being approximately 14% for the cognitive studies, and 5% (what
      would be expected from randomly generated data) for the working memory studies.
      It is likely that previous tDCS studies are substantially underpowered, and we
      provide suggestions for future research to increase the evidential value of
      future tDCS studies.

PMID- 28759804
TI  - Multidimensional apathy and executive dysfunction in amyotrophic lateral
      sclerosis.
AB  - Apathy and cognitive dysfunction are prominent symptoms of Amyotrophic lateral
      sclerosis (ALS). More specifically ALS patients show increased Initiation apathy
      a lack of motivation for self-generation of thoughts as assessed by the
      Dimensional Apathy Scale. This study aimed to investigate the cognitive
      underpinnings of apathy subtypes in ALS. We hypothesized that increased
      Initiation apathy would be associated deficits on tests of intrinsic response
      generation, such as verbal fluency. We also explored the relationship of other
      apathy subtypes to cognitive processes, in particular emotional apathy with
      emotional and social cognition deficits and executive apathy with planning and
      goal management deficits. ALS patients, and their carers (N = 30), and healthy
      matched controls, and their informants (N = 29) were recruited. All participants
      completed self- and informant/carer-rated Dimensional Apathy Scale, to quantify
      apathy subtypes (Executive, Emotional and Initiation), along with standard apathy
      and depression measures. Patients and controls completed the Edinburgh Cognitive
      and behavioural ALS Screen, and a comprehensive neuropsychological battery
      including emotional recognition, social cognition, intrinsic response generation
      tasks (verbal fluency and random number generation) and a new ecologically valid,
      computerised measure of planning and goal management. The results demonstrated
      that increased Initiation apathy was the only significantly elevated subtype in
      ALS (self-rated p < .05, informant/carer-rated p < .01). Initiation apathy was
      found to be significantly associated with verbal fluency deficit, while Emotional
      apathy was significantly associated with emotional recognition deficits. No
      associations were found between apathy subtypes and depression or in controls.
      This is the first study to show specific associations between apathy subtypes
      (Emotional and Initiation) and executive and emotional cognitive dysfunction,
      indicating possible distinct underlying mechanisms to these demotivational
      symptoms.

PMID- 28759805
TI  - Common and distinct neural mechanisms associated with the conscious experience of
      vicarious pain.
AB  - Vicarious pain perception has been an influential paradigm for investigating the
      social neuroscience of empathy. This research has highlighted the importance of
      both shared representations (i.e., involved in both experiencing first-hand
      physical pain and observing pain) and mechanisms that discriminate between self
      and other. The majority of this research has been conducted in healthy younger
      adults using a group-average approach. There are, however, known inter-individual
      differences that can contribute to vicarious experience. One factor relates to
      the degree to which individuals experience reportable pain-like
      sensations/feelings in response to seeing others in pain. Here we conduct the
      first systematic investigation of the neural basis of conscious vicarious pain in
      a large sample of participants. Using cluster analysis, we firstly demonstrate
      that consciously experiencing the pain of others is surprisingly prevalent and,
      exists in two forms: one group experiences sensory and localised pain whilst the
      other group report affective and non-localised experiences. Building on this, we
      used electroencephalography (EEG) and structural brain imaging to examine the
      neural correlates of vicarious pain in the three different groups. We find that
      the dominant electrophysiological marker used to index vicarious pain in previous
      studies (mu and beta suppression) was only found to be significant in the sensory
      and localised pain responder group (with a sensitive null result in the
      'neurotypical' group). Finally, using voxel-based morphometry (VBM) we identify a
      common differences in the two pain responder groups relative to typical adults;
      namely increased grey-matter in insula and somatosensory cortex and reduced grey
      matter in the right temporo-parietal junction (rTPJ). We suggest that the latter
      reflects a reduced ability to distinguish bodily self and other, and may be a
      common factor distinguishing conscious from unconscious vicarious experience.

PMID- 28759807
TI  - (Em)placing recovery: Sites of health and wellness for individuals with serious
      mental illness in supported housing.
AB  - This study used photo-elicitation methodology to explore how the move from
      supervised to supported housing affects recovery and community connections for
      individuals living with serious mental illness (SMI) in four Canadian cities.
      Qualitative interviews conducted in 2015 revealed five themes: (1) the
      characteristics distinguishing home from housing; (2) the importance of amenities
      offered by supported housing; (3) the connections between accessibility,
      mobility, and wellbeing; (4) the role of certain places in facilitating aspects
      of recovery such as offering hope or facilitating social connectedness; and (5)
      the concrete and metaphorical impact of changing vantage points on identity
      (re)construction. Utilizing therapeutic landscapes as an analytical framework,
      and combining insights from the health geography, and mental health (MH) housing
      and recovery literatures, this study deepens current understanding of how
      everyday places-conceptualized as therapeutic landscapes-directly and indirectly
      support MH recovery for individuals with SMI. Implications for research on
      housing, and on the spatial aspects of recovery processes are discussed.

PMID- 28759806
TI  - The effect of polymeric membrane surface on HaCaT cell properties.
AB  - The control of the surface properties is an important issue for applicability of
      polymer membranes interacting with cells. In this work, the influence of surface
      roughness and stiffness of two polymer membranes on viability and mechanical
      properties of keratinocytes was studied. Terpolimer polyglicolide,
      polycaprolactone and polylactide, (PGA-PCL-PLA) and copolymer polycaprolactone,
      polyglicolide (PGA-PCL) substrates were used for membranes fabrication. Surface
      modification - the hydrolysis of the obtained membranes was carried out. The
      analysis of membranes' surface properties revealed that RMS surface roughness and
      roughness factor of PGA-PCL-PLA membrane decreased after hydrolysis while its
      stiffness increased. In contrast, the PGA-PCL membrane stiffness was only
      slightly affected by NaOH treatment. Immortalized human keratinocytes (HaCaT)
      were grown under standard conditions on the surface of the studied membranes and
      characterized by means of atomic force microscopy and fluorescence microcopy. The
      results showed the substrate-dependent effect on cells' properties.

PMID- 28759808
TI  - Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are
      associated with chronic hepatitis B virus (HBV) infection.
AB  - OBJECTIVE: This retrospective study aimed to investigate the associations between
      the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR)
      and disease severity in patients with chronic HBV infection-related liver disease
      (CHB). METHODS: Patients with CHB were retrospectively identified. Clinical data
      for 172 HBV-infected patients and 40 healthy controls were collected from the
      electronic patient medical record system database of our hospital. RESULTS: HBV
      related-compensated-cirrhosis patients (HBV-CC patients) had a significantly
      lower mean PLR than did other patients (P<0.001). HBV-related-decompensated
      cirrhosis patients (HBV-DC patients) had a significantly higher mean NLR than did
      any other patients (P<0.001). In the entire cohort of CHB patients, significant
      correlations were observed between the PLR and both serum HBV DNA (r=0.264,
      P<0.001) and serum HBeAg (r=0.240, P=0.002). The PLR was significantly correlated
      with serum HBV DNA in both HBV-CC patients (r=-0.116, P=0.044) and HBV-DC
      patients (r=0.456, P=0.008). In HBV-Active-Carriers patients (HBV-AC patients),
      the PLR was positively correlated with serum HBeAg level (r=0.321, P=0.023). In
      HBV-DC patients, the NLR was positively correlated with serum HBeAg level
      (r=0.372, P=0.033). In the logistic regression prediction model, a predictive
      probability cutoff of 0.392 had the highest sensitivity and specificity
      (sensitivity, 91.2%; specificity, 84.0%) in distinguishing between HBV-CC and HBV
      AC patients. A NLR cutoff value of 2.94 had the highest sensitivity and
      specificity (sensitivity, 81.8%; specificity, 88.2%) in distinguishing between
      HBV-DC and HBV-CC patients. CONCLUSION: The PLR and NLR partially reflect the
      amounts of serum HBV DNA and serum HBeAg levels circulating in CHB patients. The
      logistic regression model including the PLR and age most accurately distinguished
      between HBV-CC and HBV-AC patients. The NLR may be useful for follow-up in HBV-CC
      patients to predict disease progression. In summary, the PLR and NLR provided a
      supplementary means for effectively managing chronic HBV infection and disease.

PMID- 28759809
TI  - Methane-rich saline alleviates cerulein-induced acute pancreatitis by inhibiting
      inflammatory response, oxidative stress and pancreatic apoptosis in mice.
AB  - BACKGROUND: Acute pancreatitis (AP) is a potentially life-threatening
      gastrointestinal disease involving intracellular activation of digestive enzymes
      and pancreatic acinar cell injury. The present study was performed to investigate
      whether methane-rich saline (MS) was involved in the regulation of AP. METHODS:
      MS (16ml/kg) was administered at different dosing frequencies on mice with
      cerulein-induced AP. Serum amylase, lipase and histopathological changes in the
      pancreas tissue were measured. Serum cytokine TNFalpha, IL-6, IFNgamma and IL-10
      were detected by ELISA. The mRNA levels of these inflammatory cytokines in the
      pancreas were detected by real time-PCR. Myeloperoxidase (MPO) and superoxide
      dismutase (SOD) were determined using commercial kits. Apoptosis was assessed by
      immunohistochemistry and Western blot. RESULTS: MS treatment reversed the
      increased serum level of amylase and lipase, alleviated the pathological damage
      in the pancreas, and decreased the expression of TNFalpha, IL-6, IFNgamma and IL
      10 in cerulean-induced AP mice. In addition, MPO was down-regulated and SOD was
      up-regulated in the MS treated pancreas, indicating that MS had an anti-oxidant
      effect against AP. Furthermore, MS protected pancreatic cells against cerulean
      induced apoptosis and abolished cleaved caspase-3. CONCLUSION: MS exerted anti
      inflammatory, anti-oxidant and anti-apoptotic effects on cerulein-induced AP in
      mice and may proved to be a promising therapeutic agent for the clinical
      treatment of pancreatitis.

PMID- 28759810
TI  - MiR-130b attenuates vascular inflammation via negatively regulating tumor
      progression locus 2 (Tpl2) expression.
AB  - Endothelial cell (EC) activation and dysfunction have been linked to a wide
      variety of vascular inflammatory diseases. However, the role of microRNAs in EC
      activation and inflammation remains largely unknown. In this study, we found that
      miR-130b was significantly decreased in human umbilical vein endothelial cells
      (HUVECs) after lipopolysaccharides (LPS) treatment. Forced expression of miR-130b
      inhibited the LPS-induced activation of extracellular signal-regulated kinase
      (ERK) and the inflammatory genes expression, such as interleukin (IL)-6 and tumor
      necrosis factor alpha (TNF-alpha). Furthermore, we identified that tumor
      progression locus 2 (Tpl2) is a direct target of miR-130b. Finally, in vivo
      overexpression of miR-130b via miR-130b agomir attenuates acute lung vascular
      inflammation in the LPS-induced sepsis mouse model. Taken together, our data
      demonstrated that miR-130b represses vascular inflammation via targeting Tpl2,
      suggesting that miR-130b mimics might be a promising therapeutic strategy for
      treatment of vascular inflammatory diseases.

PMID- 28759811
TI  - Impact of cationic polystyrene nanoparticles (PS-NH2) on early embryo development
      of Mytilus galloprovincialis: Effects on shell formation.
AB  - The potential release of nanoparticles (NPs) into aquatic environments represents
      a growing concern for their possible impact on aquatic organisms. In this light,
      exposure studies during early life stages, which can be highly sensitive to
      environmental perturbations, would greatly help identifying potential adverse
      effects of NPs. Although in the marine bivalve Mytilus spp. the effects of
      different types of NPs have been widely investigated, little is known on the
      effects of NPs on the developing embryo. In M. galloprovincialis, emerging
      contaminants were shown to affect gene expression profiles during early embryo
      development (from trocophorae-24 hpf to D-veligers-48 hpf). In this work, the
      effects of amino-modified polystyrene NPs (PS-NH2) on mussel embryos were
      investigated. PS-NH2 affected the development of normal D-shaped larvae at 48 hpf
      (EC50 = 0.142 mg/L). Higher concentrations (5-20 mg/L) resulted in high
      embryotoxicity/developmental arrest. At concentrations ? EC50, PS-NH2 affected
      shell formation, as shown by optical and polarized light microscopy. In these
      conditions, transcription of 12 genes involved in different biological processes
      were evaluated. PS-NH2 induced dysregulation of transcription of genes involved
      in early shell formation (Chitin synthase, Carbonic anhydrase, Extrapallial
      Protein) at both 24 and 48 hpf. Decreased mRNA levels for ABC transporter p
      glycoprotein-ABCB and Lysozyme were also observed at 48 hpf. SEM observations
      confirmed developmental toxicity at higher concentrations (5 mg/L). These data
      underline the sensitivity of Mytilus early embryos to PS-NH2 and support the
      hypothesis that calcifying larvae of marine species are particularly vulnerable
      to abiotic stressors, including exposure to selected types of NPs.

PMID- 28759812
TI  - Bioaccumulation of PCBs from microplastics in Norway lobster (Nephrops
      norvegicus): An experimental study.
AB  - Plastic debris acts as a sorbent phase for hydrophobic organic compounds like
      polychlorinated biphenyls (PCBs). Chemical partitioning models predict that the
      ingestion of microplastics with adsorbed chemicals in the field will tend not to
      result in significant net desorption of the chemical to the organism's tissues.
      This is expected due to the often limited differences in fugacity of the chemical
      between the indigestible plastic materials and the tissues, which are typically
      already exposed in the same environment to the same chemicals as the plastic.
      However laboratory trials validating these model predictions are scarce. In this
      study, PCB-loaded microplastics were offered to field-collected Norway lobsters
      (Nephrops norvegicus) during in vivo feeding laboratory experiments. Each
      ingestion experiment was repeated with and without loading a mixture of ten PCB
      congeners onto plastic microspheres (MS) made of polyethylene (PE) and
      polystyrene (PS) with diameters of either 500-600 MUm or 6 MUm. We observed that
      the presence of chemicals adsorbed to ingested microplastics did not lead to
      significant bioaccumulation of the chemicals in the exposed organisms. There was
      a limited uptake of PCBs in Nephrops tail tissue after ingestion of PCB-loaded PE
      MS, while almost no PCBs were detected in animals exposed to PS MS. In general,
      our results demonstrated that after 3 weeks of exposure the ingestion of plastic
      MS themselves did not affect the nutritional state of wild Nephrops.

PMID- 28759813
TI  - High proportions of inorganic arsenic in Laminaria digitata but not in
      Ascophyllum nodosum samples from Ireland.
AB  - Seaweed can accumulate inorganic arsenic (iAs) from seawater as hydrogen arsenate
      (HAsO42-) in place of the phosphate anion (HPO42-). While it is rapidly
      metabolised to organoarsenic species, predominantly arsenosugars and
      arsenolipids, iAs may be present in seaweed biomass and this poses a potential
      health concern for consumers of seaweed products. Here, the distribution of total
      (AsTOT) and iAs was determined in thallus parts of the kelp Laminaria digitata
      and the intertidal fucoid Ascophyllum nodosum (both Phaeophyceae) using
      inductively-coupled plasma mass spectrometry (ICP-MS) and high performance liquid
      chromatography - ICP-MS (HPLC-ICP-MS). AsTOT ranged from 36 to 131 mg kg-1 dry
      weight (DW) in L. digitata, and from 38 to 111 mg kg-1 DW in A. nodosum, with no
      statistically significant differences between different thallus parts. iAs was
      detected in all A. nodosum samples, comprising less than 1% of the AsTOT content.
      Concentrations of iAs in L. digitata were significantly higher, ranging from 2.2
      to 87 mg kg-1, increasing through the thallus from the stipe to the decaying
      distal blades. iAs comprised more than 50% of AsTOT in the middle to decaying
      distal blades. This finding has potential implications for harvesting, processing
      and use of Laminaria digitata in agri-, food and health applications.

PMID- 28759814
TI  - Evaluation of hydrogen bond networks in cellulose Ibeta and II crystals using
      density functional theory and Car-Parrinello molecular dynamics.
AB  - Crystal models of cellulose Ibeta and II, which contain various hydrogen bonding
      (HB) networks, were analyzed using density functional theory and Car-Parrinello
      molecular dynamics (CPMD) simulations. From the CPMD trajectories, the power
      spectra of the velocity correlation functions of hydroxyl groups involved in
      hydrogen bonds were calculated. For the Ibeta allomorph, HB network A, which is
      dominant according to the neutron diffraction data, was stable, and the power
      spectrum represented the essential features of the experimental IR spectra. In
      contrast, network B, which is a minor structure, was unstable because its
      hydroxymethyl groups reoriented during the CPMD simulation, yielding a different
      crystal structure to that determined by experiments. For the II allomorph, a HB
      network A is proposed based on diffraction data, whereas molecular modeling
      identifies an alternative network B. Our simulations showed that the interaction
      energies of the cellulose II (B) model are slightly more favorable than model
      II(A). However, the evaluation of the free energy should be waited for the
      accurate determination from the energy point of view. For the IR calculation,
      cellulose II (B) model reproduces the spectra better than model II (A).

PMID- 28759815
TI  - Tunable stereoselectivity in the synthesis of alpha- and beta-aryl glycosides
      using 1,2-alpha-anhydrosugars as glycosyl donors.
AB  - The stereochemical course of O-glycosidation of 1,2-alpha-d-anhydrosugars (glycal
      epoxides) with phenols can be tuned by varying the metal ion of the base. While
      the reaction of 1,2-alpha-d-anhydrosugars with phenols mediated by
      trimethylaluminium leads exclusively to 1,2-cis-alpha-O-aryl glycosides, similar
      reaction mediated by caesium carbonate gives exclusively 1,2-trans-beta-O-aryl
      glycosides. In contrast, reaction with phenoxides generated from Grignard reagent
      and calcium salts affords mixture of the anomers.

PMID- 28759816
TI  - Phospholamban immunostaining is a highly sensitive and specific method for
      diagnosing phospholamban p.Arg14del cardiomyopathy.
AB  - Phospholamban (PLN) p.Arg14del cardiomyopathy is associated with an increased
      risk of malignant ventricular arrhythmias and severe heart failure and a poor
      prognosis from late adolescence. It can be diagnosed in whole heart specimens,
      but rarely in right ventricular biopsy specimens, by PLN immunohistochemistry
      showing PLN-containing aggregates concentrated in cardiomyocytes in dense
      perinuclear aggresomes. The purpose of this study was to determine whether PLN
      immunohistochemistry can be used to diagnose PLN p.Arg14del cardiomyopathy using
      apical left ventricular myocardial specimens harvested during left ventricular
      assist device (LVAD) implantation. At that stage, a genetic diagnosis, which may
      guide treatment and referral of family members for further investigation, is
      frequently not established yet. Included were myocardial specimens from 30
      diverse genetic cardiomyopathy cases with known variants (9 carriers of the
      pathogenic PLN p.Arg14del variant, 18 cases with other pathogenic or likely
      pathogenic variants in cardiomyopathy-related genes, and 3 with only variants of
      unknown significance). Immunohistochemical analysis revealed typical dense
      perinuclear globular PLN-positive aggregates, representing aggresomes, in all
      nine PLN p.Arg14del cases. In 20 non-PLN cases, PLN-staining was absent. In one
      non-PLN case, one of the two independent observers misinterpreted PLN staining of
      heavily wrinkled nuclear membranes of cardiomyocytes as perinuclear PLN
      aggregates. In this genetic cardiomyopathy cohort, PLN Immunohistochemical
      analysis in LVAD biopsies was found to be a highly sensitive (100%) and specific
      (95%) method for demonstration of PLN protein aggregates in PLN p.Arg14del
      cardiomyopathy. In clinical practice, PLN immunohistochemical analysis of LVAD
      specimens can be of incremental value in the diagnostic workup of this
      cardiomyopathy, even more so if genetic analysis is not readily available.

PMID- 28759818
TI  - Histological topography of the atrioventricular node and its extensions in
      relation to the cardiothoracic surgical landmarks in normal human hearts.
AB  - BACKGROUND: Atrioventricular (AV) nodal injury which results in cardiac
      conduction disorders is one of the potential complications of heart valve
      surgeries and radiofrequency catheter ablations. Understanding the topography of
      the AV conduction system in relation to the tricuspid and mitral valves will help
      in reducing these complications. METHODS: A tissue block of 3cmx4cm, which
      contain the AV node, bundle of His and the AV nodal extensions, was excised at
      the AV septal junction in 20 apparently normal human hearts. The block was
      divided into three equal segments through vertical incisions perpendicular to the
      insertion of the septal leaflet of the tricuspid valve. Each segment was
      processed and stained with H&E and Gomori to study the different parts of the AV
      conduction system. RESULTS: The lower pole of the AV node was located vertically
      above the tricuspid septal leaflet (TSL) in 100% (20/20) of cases and at the
      level of the muscular interventricular septum in 65% (13/20) of cases. The upper
      pole of the compact AV node was located at the level of the mitral valve leaflet
      (MVL) in 50% (10/20) of cases. The penetrating bundle of His was seen at the
      level of the TSL, while the branching bundle of His was situated 1.9+/-1.5 mm
      inferior to the TSL. The right and left posterior extensions of the AV node
      spanned from the MVL to 2.9+/-1.3 mm above the TSL. CONCLUSIONS: A rectangular
      area (2.5 mm * 12 mm) in the Koch's triangle was devoid of AV nodal tissue and
      could be labeled as a safe area with no risk of conduction defects during valve
      surgeries. Information on the separation of AV nodal extensions from the TSL, MVL
      and muscular interventricular septum may play a crucial role in guiding and
      improving the safety of radiofrequency ablations.

PMID- 28759817
TI  - Left atrial remodeling, hypertrophy, and fibrosis in mouse models of heart
      failure.
AB  - Left ventricular dysfunction increases left atrial pressures and causes atrial
      remodeling. In human subjects, increased left atrial size is a powerful predictor
      of mortality and adverse events in a broad range of cardiac pathologic
      conditions. Moreover, structural remodeling of the atrium plays an important role
      in the pathogenesis of atrial tachyarrhythmias. Despite the potential value of
      the atrium in assessment of functional endpoints in myocardial disease, atrial
      pathologic alterations in mouse models of left ventricular disease have not been
      systematically investigated. Our study describes the geometric, morphologic, and
      structural changes in experimental mouse models of cardiac pressure overload
      (induced through transverse aortic constriction), myocardial infarction, and
      diabetes. Morphometric and histological analysis showed that pressure overload
      was associated with left atrial dilation, increased left atrial mass, loss of
      myofibrillar content in a subset of atrial cardiomyocytes, atrial cardiomyocyte
      hypertrophy, and atrial fibrosis. In mice undergoing nonreperfused myocardial
      infarction protocols, marked left ventricular systolic dysfunction was associated
      with left atrial enlargement, atrial cardiomyocyte hypertrophy, and atrial
      fibrosis. Both infarcted animals and pressure overloaded mice exhibited
      attenuation and perturbed localization of atrial connexin-43 immunoreactivity,
      suggesting gap junctional remodeling. In the absence of injury, obese diabetic
      db/db mice had diastolic dysfunction associated with atrial dilation, atrial
      cardiomyocyte hypertrophy, and mild atrial fibrosis. Considering the challenges
      in assessment of clinically relevant functional endpoints in mouse models of
      heart disease, study of atrial geometry and morphology may serve as an important
      new tool for evaluation of ventricular function.

PMID- 28759819
TI  - Polymer coating embolism from intravascular medical devices - a clinical
      literature review.
AB  - Over the past three decades, lubricious (hydrophobic and/or hydrophilic) polymer
      coated devices have been increasingly adopted by interventional physicians and
      vascular surgeons to access and treat a wider range of clinical presentations.
      Recent clinical literature highlights the presence of polymer coating emboli
      within the anatomy - a result of coating separation from an intravascular device 
      and associates it with a range of adverse clinical sequelae. The 2015 U.S. Food
      and Drug Administration safety communication titled "Lubricious Coating
      Separation from Intravascular Medical Devices" acknowledges these concerns and
      concludes that it will work with stakeholders to develop nonclinical test
      methodologies, establish performance criteria, and identify gaps in current
      national and international device standards for coating integrity performance.
      Despite this communication and multiple case reports from interventional
      physicians, pathologists, dermatologists and other involved physician
      specialties, polymer coating embolism remains clinically underrecognized. This
      article consolidates the available literature on polymer coating embolism (1986
      2016) and highlights the following relevant information for the physician: (a)
      the history and elusive nature of polymer coating embolism; (b) potential
      incidence rates of this phenomenon; (c) reported histologic findings and clinical
      effects of polymer emboli in the anatomy; (d) the importance of the collaborative
      clinician-pathologist partnership to report polymer embolism findings; and (e)
      the importance to study particulate release from intravascular devices so as to
      further understand and potentially evolve coated interventional technologies.
      Preliminary research on coatings highlights the potential of using iterations of
      coatings on medical devices that attain the desired therapeutic result and
      mitigate or eliminate particulates altogether.

PMID- 28759820
TI  - Winning the battle, but losing the war: mechanisms and morphology of cancer
      therapy-associated cardiovascular toxicity.
AB  - In the United States, the lifetime risk of a cancer diagnosis is nearly 40%; in
      2016, that represents almost 1.6 million new patients, and despite advances in
      early diagnosis and treatment, roughly 35% will ultimately die of their
      malignancy. Fortunately, the number of patients living with a cancer diagnosis
      also continues to expand, anticipated to be more than 19 million in less than a
      decade. In calculating the relative risks and benefits of therapy, it is
      therefore important to consider the morbidity and mortality associated with
      antitumor therapy itself. Significantly, excluding demise due to the malignancy
      itself, treatment-induced adverse cardiovascular events are the leading cause of
      death in cancer patients. Chemotherapy, targeted therapies, immune checkpoint
      inhibition, and radiation therapy can all adversely impact cardiac function, and
      their effects can be synergistic. Consequently, it is important that possible
      side effects of therapy be recognized and effectively controlled. This review
      highlights the mechanisms and histopathologic findings associated with common
      forms of potentially cardiotoxic cancer therapy including anthracyclines,
      tyrosine kinase inhibitors, and most recently immune checkpoint (PD-1)
      inhibitors. Although for many cases the histologic findings are nonspecific, in
      the appropriate clinical context, therapeutic cardiotoxicity can be inferred and
      the treatment approach refined appropriately.

PMID- 28759821
TI  - Low levels of hepatitis C diagnosis and testing uptake among people who inject
      image and performance enhancing drugs in England and Wales, 2012-15.
AB  - INTRODUCTION: People injecting image and performance enhancing drugs (IPEDs) have
      traditionally not been perceived as being at high risk of hepatitis C virus (HCV)
      infection. However, recent studies indicate the HCV antibody (anti-HCV)
      prevalence in this group is 10-times that in the general population. HCV testing
      uptake and undiagnosed infections are examined using data from a voluntary
      unlinked-anonymous survey. METHOD: People injecting IPEDs across England and
      Wales completed a short bio-behavioural survey (2012-15). Anti-HCV status and
      self-reports of HCV testing were used in the analysis. RESULTS: The participants
      median age was 31 years, 98% were men, 14% had also injected psychoactive drugs
      and the anti-HCV prevalence was 4.8% (N=564). Among those who had never injected
      psychoactive drugs the anti-HCV prevalence was 1.4%; among those who had recently
      injected psychoactive drugs (preceding 12 months) prevalence was 39% and among
      those who had done this previously 14% (p<0.001). Overall, 37% had been tested
      for HCV: among those who had recently injected psychoactive drugs 78% had been
      tested, as had 56% of those who had injected psychoactive drugs previously; 33%
      of those never injecting psychoactive drugs were tested (p<0.001). Overall, 44%
      of those with anti-HCV were aware of this; however, only 14% of those who had
      never injected psychoactive drugs were aware. CONCLUSIONS: One-in-twenty people
      who inject IPEDs have anti-HCV. HCV infections among those who had never injected
      psychoactive drugs were mostly undiagnosed, though this group had a lower
      prevalence. Targeted HCV testing interventions are also needed for those
      injecting IPEDs.

PMID- 28759823
TI  - The effectiveness of the Pain Resource Nurse Program to improve pain management
      in the hospital setting: A cluster randomized controlled trial.
AB  - BACKGROUND: The Pain Resource Nurse program is a widely disseminated, evidence
      based, nursing staff development program, designed to improve pain management in
      hospitals. The program has shown promising results, but has never been tested
      with a rigorous research design. OBJECTIVES: Our objective was to test the
      effectiveness of the Pain Resource Nurse program. Hypothesized outcomes included
      improvements in nurses' knowledge, attitudes, and assessment practices, and in
      patients' participation in decision-making, adequacy of pain management, pain
      severity, time spent in severe pain, pain interference, and satisfaction. DESIGN:
      Cluster randomized controlled trial. SETTING: A 650-bed university hospital in
      Iceland Participants: The sample consisted of a) patients >=18 years of age,
      native speaking, hospitalized for at least 24h, alert and able to participate;
      and b) registered nurses who worked on the participating units. METHODS: Twenty
      three surgical and medical inpatient units were randomly assigned to the Pain
      Resource Nurse program (n=12) or to wait list control (n=11). The American Pain
      Society Outcome Questionnaire and the Knowledge and Attitudes Survey were used to
      collect data from patients and nurses respectively. Baseline data (T1) for
      patients were collected simultaneously on all units, followed by data collection
      from nurses. Then randomization took place, and the Pain Resource Nurse program
      was instituted. Ten months later, follow up (T2) data were collected, after which
      the nurses on the control group units received the Pain Resource Nurse program.
      RESULTS: At baseline, data were collected from 305 of the 396 eligible patients
      and at follow up from 326 of the 392 eligible patients, a 77% and 83% response
      rate respectively. At baseline, 232 of 479 eligible nurses responded and at
      follow-up 176 of the eligible 451 nurses responded, a 49% and 39% response rate,
      respectively. A nested mixed model analysis of covariance revealed that the
      intervention was successful in changing pain assessment practices, with pain
      assessment using standardized measures increasing from 13% to 25% in the
      intervention group while decreasing from 21% to 16% in the control group. None of
      the other hypothesized improvements were found. CONCLUSIONS: The Pain Resource
      Nurse program was successful in improving nurses' use of standardized measures
      for pain assessment. No effects were found on patient outcomes; pain was both
      prevalent and severe at both time points. Only minimal improvements were noted in
      response to this evidence-based staff development program. Changes in pain
      management practices remain a challenge in clinical settings.

PMID- 28759824
TI  - Are skin antiseptics for blood culture collection really equal? Commentary on
      Liu, W., et al., 2016 "Skin antiseptics in venous puncture site disinfection for
      preventing blood culture contamination: A Bayesian network meta-analysis of
      randomized controlled trials".

PMID- 28759825
TI  - Binding free energy calculations using MMPB/GBSA approaches for PAMAM-G4-drug
      complexes at neutral, basic and acid pH conditions.
AB  - Dendrimers are synthetic macromolecules with a highly-branched structure and high
      concentration of surface groups. Among dendrimers, Poly(amidoamine) (PAMAM) has
      received substantial attention as a novel drug carrier and delivery system.
      Depending on the generation and type of terminal groups, dendrimer toxicity could
      change and include cytotoxicity. Although PAMAM is water soluble, molecular
      modeling of the dendrimer-drug complex is considered challenging for exploring
      the conformational mobility of dendrimers and atomic specific interactions during
      the dendrimer-drug association. However, conventional protocols for predicting
      binding affinities have been designed for small protein molecules or protein
      protein complexes that can be applied to study the dendrimer-drug association. In
      this work, we performed docking calculations for a set of 94 previously reported
      compounds on PAMAM of fourth generation (G4-PAMAM) to select six compounds,
      cromoglicic acid (CRO) - a mast cell stabilizer, Fusidic acid (FUS) - a
      bacteriostatic antibiotic, and Methotrexate (MTX) - a chemotherapy agent and
      immune system suppressant, which have the highest affinities for G4-PAMAM, and
      Lidocaine (LDC) - used to numb tissue in a specific area and for ventricular
      tachycardia treatment, Metoprolol (MET) - a beta1 receptor blocker, and Pindolol
      (PIN) - a beta blocker, which have the lowest affinities for the G4-PAMAM
      dendrimer, to perform MD simulations combined with the molecular mechanics
      generalized/Poisson-Boltzmann surface area MMGBSA/MMPBSA approach to investigate
      the interactions of generating 4 charge-neutral, charge-basic and charge-acid G4
      PAMAM dendrimers. In addition, to validate these theoretical G4-PAMAM-drug
      complexes, the complexes were experimentally conjugated to determine their
      stability in aqueous solubility studies immediately and over one year. Our
      results show that among the different commercial drugs, both charged and neutral
      PAMAM have the most favorable binding free energies for CRO, MTX, and FUS, which
      appears to be due to a complex counterbalance of electrostatics and van der Waals
      interactions. These theoretical and aqueous solubility studies supported the high
      affinity of methotrexate for the G4-PAMAM-drug due to its carboxyl and aryl
      moieties that favor its accommodation by noncovalent interactions.

PMID- 28759826
TI  - Duodenal rupture due to giant inguinal hernia: A case report.
AB  - INTRODUCTION: Giant inguinal hernia is unusual, and duodenal rupture accompanying
      it is particularly very rare and significantly hard to manage surgically.
      PRESENTATION OF CASE: An 81-year-old man was admitted to our institution with
      upper abdominal pain. He had tenderness of the upper mid abdomen and a bilateral
      large inguinal hernia but he did not have pain in the inguinal-scrotal area.
      Computed tomography (CT) showed slight dilatation of the small bowel and stomach.
      There were no remarkable signs of incarceration of the inguinal hernia.
      Therefore, he was admitted to the internal ward. On the second day in hospital,
      he suddenly went into shock. CT revealed that there was free air and ascites in
      the inguinal hernia and therefore an emergency operation was performed. The
      tranverse colon, ascending colon, and ileum were incarcerated, and perfolation of
      the cecum was found. We also detected duodenal rupture at the inferior duodenal
      angle. We resected the terminal ileal (almost 90cm) and ileocecal area, followed
      by side-to-side anastomosis of duodenum and jejunum. We only repaired the
      peritoneum at the internal hernia ring. After the operation, despite intensive
      care therapy, this patient passed away on the 18th postoperative day. DISCUSSION:
      The mesocolon and third portion of the duodenum were strongly pulled down into
      giant inguinal hernia, probably causing the rupture of the inferior duodenal
      angle. CONCLUSION: Giant inguinal hernia possibly provokes duodenal rupture and
      therefore should definitively be repaired if feasible.

PMID- 28759822
TI  - Treatment of late sequelae after radiotherapy for head and neck cancer.
AB  - Radiotherapy (RT) is used to treat approximately 80% of patients with cancer of
      the head and neck. Despite enormous advances in RT planning and delivery, a
      significant number of patients will experience radiation-associated toxicities,
      especially those treated with concurrent systemic agents. Many effective
      management options are available for acute RT-associated toxicities, but
      treatment options are much more limited and of variable benefit among patients
      who develop late sequelae after RT. The adverse impact of developing late tissue
      damage in irradiated patients may range from bothersome symptoms that negatively
      affect their quality of life to severe life-threatening complications. In the
      region of the head and neck, among the most problematic late effects are impaired
      function of the salivary glands and swallowing apparatus. Other tissues and
      structures in the region may be at risk, depending mainly on the location of the
      irradiated tumor relative to the mandible and hearing apparatus. Here, we review
      the available evidence on the use of different therapeutic strategies to
      alleviate common late sequelae of RT in head and neck cancer patients, with a
      focus on the critical assessment of the treatment options for xerostomia,
      dysphagia, mandibular osteoradionecrosis, trismus, and hearing loss.

PMID- 28759827
TI  - Double cystic duct, a review of literature with report of a new case.
AB  - INTRODUCTION: Although cystic duct variation is quite common, duplication of
      cystic duct is an extreme rare variant. We report a case of double cystic duct
      with literature review. A 33-year old female presented with right upper quadrant
      pain of three day duration, associated with nausea and poor appetite. The patient
      reported previous three attacks of right upper quadrant pain within the last two
      years. On examination: Murphy's sign was positive and the right upper quadrant
      was tender. Abdominal ultrasound showed multiple gall stones. Oesophago-gastro-
      duodenoscopy was normal. Under general anesthesia, four port formal laparoscopy
      was done, double cystic duct was found. Histopathological examination showed
      features of chronic cholecystitis. CONCLUSION: double cystic duct is a very rare
      variant of the cystic duct anomaly. Identification pre or intraoperatively is
      very important to prevent ductal injury.

PMID- 28759828
TI  - What's new on primary Hodgkin's lymphoma of the breast? A case report and review
      of the literature.
AB  - INTRODUCTION: According to literature, primary Hodgkin's lymphomas of the breast
      represent one of the rarer entity in the primary breast lymphoma (PBL) scenario.
      This is the reason why these tumors are insidious in mammary oncology.
      PRESENTATION OF THE CASE: We report a case of HL primitive breast in an elderly
      patient in whom radiology suspected an advanced breast cancer with ipsilateral
      axillary involvement and in which the fine-needle aspiration came back not
      significant. DISCUSSION: Eighteen cases of primary Hodgkin's lymphoma of the
      breast has been described in Literature in a very large period of time: from 1928
      to 2016. The nodular sclerosis type is the most frequent histological variant.
      CONCLUSION: Their rarity together with the fact that radiological investigations
      are not significant for the purpose of an exact diagnosis, make these lesions
      extremely difficult to identify.

PMID- 28759829
TI  - Adventitial cystic disease of the popliteal artery treated by bypass graft
      utilizing the short saphenous vein: A case report.
AB  - INTRODUCTION: Adventitial cystic disease is relatively rare vascular disease,
      frequently occurred in the popliteal artery. No definitive treatment has been
      established yet. PRENTATION OF CASE: A 53-year-old woman presenting intermittent
      claudication of the right leg was diagnosed as adventitial cystic disease of
      popliteal artery. Percutaneous balloon dilation yielded an immediate recurrence.
      The disease was successfully treated by bypass grafting utilizing the short
      saphenous vein to replace the part of the popliteal artery containing the
      adventitial cyst. No postoperative complication was found six months after
      surgery. DISCUSSION: Comparing to a great saphenous vein, a short saphenous vein
      as a material of bypass graft has a significant advantage, as only a single
      surgical field is necessary. CONCLUSION: We propose that bypass graft surgery
      employing a short saphenous vein is worth considering as a treatment of
      adventitial cystic disease at the popliteal artery.

PMID- 28759830
TI  - Forearm nonunion caused by hyperparathyroidism with 7 years follow up: A case
      report.
AB  - INTRODUCTION: We report a patient who developed nonunion of both bones of the
      forearm associated with hyperparathyroidism (HPT). PRESENTATION OF CASE: The
      patient was a 71-year-old female who previously fell and hit her left hand on the
      ground. At 2 years after injury the patient visited our hospital, since she
      became aware of instability of the left forearm without an inducer due to
      nonunion of the radioulnar diaphysis. The patient was surgically treated to
      acquire forearm support. Surgery for nonunion was applied only to the ulna. To
      acquire an elbow joint flexion angle, an about 30 degrees  angle was added to the
      false joint region. At one year after surgery, blood testing suggested HPT,
      however, the parathyroid mass was not excised following the current guidelines
      for management of HPT. At 7 years after surgery, the elbow range of motion, VAS
      and the Q-DASH score were improved. Weight-bearing by the forearm became
      possible, and the patient can perform pronation and supination at the radial
      nonunion. DISCUSSION: We learned from this case that it is necessary to
      immediately perform close examination to identify the presence or absence of
      primary disease causing insufficiency fracture, such as HPT. For treatment of
      nonunion of the 2 forearm bones in this elderly female, osteosynthesis of the
      ulna alone achieved sufficient osteal support without osteosynthesis of the
      radius, and the postoperative course was favorable. CONCLUSION: We presented here
      a rare case of nonunion of both bones of the forearm associated with HPT.

PMID- 28759831
TI  - Pulsed UV laser-induced modifications in optical and structural characteristics
      of alpha-irradiated PM-355 SSNTD.
AB  - Pre- and postalpha-exposed PM-355 detectors were irradiated using UV laser with
      different number of pulses (100, 150, 200, 300, and 400). UV laser beam energy of
      20mJ per pulse with a pulse width of 9ns was incident on an area of 19.6mm2 of
      the samples. XRD spectra indicated that for both reference and UV-irradiated
      samples, the structure is amorphous, but the crystallite size increases upon UV
      irradiation. The same results were obtained from SEM analysis. Optical properties
      of PM-355 polymeric solid-state nuclear track detectors were also investigated.
      Absorbance measurements for all PM-355 samples in the range of 200-400nm showed
      that the absorption edge had a blue shift up to a certain value, and then, it had
      an oscillating behavior. Photoluminescence spectra of PM-355 at 250nm revealed a
      decrease in the broadband peak intensity as a function of the number of UV
      pulses, while the wavelengths corresponding to the peaks had random shifts.

PMID- 28759832
TI  - Activity-specific pathways among duration of organized activity involvement,
      social support, and adolescent well-being: Findings from a nationally
      representative sample.
AB  - Using data from N = 10,148 American youth (Mage = 15.18) who participated in the
      National Comorbidity Survey Adolescent Supplement, we tested whether duration of
      involvement in specific organized activities was associated with different
      sources of social support, and whether these links explained the health-related
      benefits affiliated with participation. Duration of involvement in certain
      activities was differentially associated with support from peers, teachers, and
      other adults, and many of these links partially mediated associations between
      involvement and well-being. Specifically, greater duration of sports involvement
      was indirectly associated with higher self-esteem and greater physical activity
      through greater adult support. Greater duration of club involvement was
      indirectly associated with greater physical activity through higher adult support
      and greater duration of music involvement was indirectly associated with lower
      substance use and greater self-esteem through greater teacher support. Prolonged
      engagement in specific activities may cultivate certain types of supportive
      relationships, which may promote adolescent well-being.

PMID- 28759833
TI  - Anti-oxidative treatment with vitamin E improves peripheral vascular function in
      patients with diabetes mellitus and Haptoglobin 2-2 genotype: A double-blinded
      cross-over study.
AB  - Vascular dysfunction in both conduit arteries and small vessels is a major
      contributor to the development of cardiovascular disease (CVD) in diabetes
      mellitus (DM). In diabetes there is a process of systemic chronic inflammation
      accompanied by high oxidative stress causing a subsequent decrease in vascular
      reactivity and negatively affect the metabolic processes responsible for
      functioning of the microvasculature. Vitamin E is classified as an antioxidant
      due to its ability to scavenge lipid radicals and terminate oxidative chain
      reactions. We conducted a double-blinded cross-over study with vitamin E versus
      placebo in individuals with type 2DM and the Hp2-2 genotype and assessed
      different aspects of peripheral vascular function in these patients. Twenty
      patients completed the study with 10 individuals in each study cohort. We were
      able to show significant improvement of indirect indices of vascular function
      following 8weeks of treatment with vitamin E. This improvement was consistent for
      weeks even after stopping the vitamin E treatment. We concluded that a
      pharmacogenomic rationale utilizing the Hp genotype might potentially provide
      cardiovascular benefit with vitamin E.

PMID- 28759834
TI  - The effects of intrauterine infusion of peanut oil on endometrial health,
      salivary cortisol and interovulatory period in mares.
AB  - Intrauterine infusion of peanut oil at Day 10 post-ovulation has been reported to
      prolong dioestrus in mares. However, the effects of peanut oil treatment on the
      endometrium and whether the technique is painful have not been assessed. The
      objectives of this study were, (i) to determine the effect of intrauterine
      infusion of peanut oil on endometrial health, (ii) to determine whether use of
      intrauterine peanut oil is painful and (iii) to confirm that peanut oil causes
      prolonged dioestrus. Six mares aged 3-12 years old were used in a cross-over
      design with each mare administered both 1 ml of intrauterine peanut oil and a
      sham treatment on different oestrous cycles. The effect of intrauterine infusion
      of 1 ml peanut oil or sham treatment were measured using interovulatory period,
      uterine fluid accumulation as determined by transrectal ultrasonography, serum
      progesterone levels, endometrial Kenney biopsy scores and histological features,
      endometrial eosinophil numbers and salivary cortisol measurements. The individual
      mare response to intrauterine infusion of peanut oil was variable. Peanut oil
      infusion did not statistically prolong the luteal phase, nor elevate salivary
      cortisol levels but did cause superficial erosion of the endometrial surface
      epithelium in all mares and significantly increased eosinophil numbers in the
      endometrium (P = 0.0068). The Kenney grade for biopsies from 2/6 mares worsened
      transiently following infusion. In conclusion, intra-uterine peanut oil does not
      statistically increase the duration of the luteal phase but results in an
      inflammatory response and increase in endometrial eosinophil numbers suggesting
      treatment may be associated with a hypersensitivity-type reaction. Those
      contemplating using peanut oil to suppress oestrus should also be aware of the
      legislative and regulatory implications.

PMID- 28759835
TI  - Characterizing the reproductive biology of the female pygmy hippopotamus
      (Choeropsis liberiensis) through non-invasive endocrine monitoring.
AB  - The pygmy hippopotamus (Choeropsis liberiensis) is endangered in the wild and
      very little is known about its reproductive biology. In zoological facilities,
      this species experiences a number of reproductive issues that complicate breeding
      management, including a high rate of stillbirths and failure of many pairs to
      reproduce. We conducted a comprehensive study to evaluate reproductive cycles and
      pregnancy in this species using enzyme immunoassays (EIAs) for fecal hormone
      metabolite analysis. Fresh fecal samples were collected twice weekly for a one to
      three year period from 36 female pygmy hippos housed at 24 zoological
      institutions. Samples were analyzed in three separate laboratories. Three
      progestogen metabolite EIAs (Pg-diol: 5beta-pregnane-3alpha,20alpha-diol 3HS:BSA;
      PdG: pregnanediol-3-glucuronide R13904; mono-P4: Quidel clone 425) and three
      estrogen metabolite EIAs (E2a: estradiol-17beta-OH 17-HS:BSA; E2b: estradiol
      17beta R0008; E2c: estradiol 17beta R4972) accurately reflected reproductive
      events. Average estrous cycle length was 31.8 +/- 7.4 days based on estrogen
      metabolite peaks and 30.9 +/- 7.3 days based on nadir to nadir progestogen
      metabolite concentrations. Cyclical patterns in both estrogen and progestogen
      metabolites were detected throughout the year, indicating a lack of seasonality.
      Estrogen metabolite peaks were also observed during pregnancy and lactation,
      suggesting that follicular development occurs during both reproductive states.
      Pregnancy was most reliably demonstrated by elevation in progestogen metabolites
      (Pg-diol or PdG) in the second half of gestation. Average gestation length based
      on breeding to calving date was 203 +/- 4 days for 15 pregnancies. This
      comprehensive overview of the reproductive biology of the female pygmy hippo
      provides valuable data for guiding long-term breeding management for this
      endangered species and serves as a baseline for future studies addressing the
      potential influence of social structure, diet, body condition, and other
      husbandry factors on estrous cycling and reproduction.

PMID- 28759836
TI  - Comparison of celioscopy and histological examinations to assess male gonadal
      health and functionality in adults and immature wild raptors.
AB  - Celioscopy is routinely used in birds for sex determination and diagnostic
      purposes. Aim of this work was to validate celioscopy for the assessment of male
      gonads functionality in wild raptors, comparing the results of direct observation
      with morphometrical and histological characteristics. The work was done at the
      'Centro Animali Non Convenzionali' of the University of Turin, Italy, on 31
      endoscopically evaluated raptors that died or were euthanized. Through
      celioscopic observation, the birds were classified in adults or immatures and
      maturity categories were defined according to the adrenal-gonad size ratio and to
      the degree of blood filling of testicular vessels. The gonads were removed
      immediately after death/euthanasia and measured. Albuginea tunic thickness,
      diameter of seminiferous tubules, number of meiosis figures, tubular development
      degree, tubular degeneration degree and germinal cells production degree were
      evaluated. Testicular size tended to increase from immature to adult birds and
      from 'out of' to 'in' breeding season; albuginea tunic thickness tended to be
      higher out of the reproductive season while diameter of the seminiferous tubules,
      germinative epithelium thickness and number of meiosis figures were higher in the
      breeding season. In season adults generally showed higher values in tubular
      development and germinal cells production, and lower degrees of tubular cells
      degeneration and fibrosis. From the interpretation of all the morphometrical and
      histological aspects, a general reproductive degree of activity was given to the
      birds and compared with celioscopic results. A perfect concordance was found in
      23 out of 31 cases and a good concordance in six ones; histology could describe
      obviously better sub-clinical conditions undetectable at direct observation.
      These preliminary results suggest that celioscopy could be a useful tool to
      assess male gonads functionality in wild raptors, with the future goal to select
      the better potential semen donors.

PMID- 28759837
TI  - Dynamics of pre- and post-insemination progesterone profiles and insemination
      outcomes determined by an in-line milk analysis system in primiparous and
      multiparous Canadian Holstein cows.
AB  - The objective was to evaluate in-line milk progesterone (mP4) data to determine
      dynamics of pre- and post-insemination mP4 profiles and their associations with
      parity and outcomes of artificial insemination (AI) in Holstein cows. Milk
      progesterone (ng/mL) was quantified at pre-determined time points before and
      after AI through an automated in-line milk analysis system (Herd NavigatorTM,
      DeLaval International, Tumba, Sweden). Only AI (~d0; n = 605) preceded by an mP4
      decline (at least two samples of mP4 >=5 ng/mL followed by at least one sample <5
      ng/mL; d-2) were evaluated. Maximum mP4 attained between d-15 and d-2 (PrePeak),
      d-2, d5, d10, d14, maximum mP4 attained within 21d post-AI (PostPeak), and rate
      of-daily-change between mP4 time points (ng/mL/d) were analyzed. Primiparous and
      multiparous cows were classified by AI outcomes based on post-AI mP4 profiles
      into three groups: (1) non-pregnant (OPEN; mP4-decline <= 30d post-AI), (2)
      presumed-pregnant (PREG; no mP4-decline until 55d post-AI), and (3) presumed
      pregnancy loss (P-LOSS; mP4-decline between 31 and 55d post-AI). For profile
      comparisons, smoothed mP4 data were analyzed using mixed linear models.
      Primiparous cows had greater (P < 0.01) mP4 than multiparous cows at d5 (4.6 +/-
      0.2 vs. 2.8 +/- 0.1), 10 (11.1 +/- 0.4 vs. 7.6 +/- 0.2), 14 (19.7 +/- 0.4 vs.
      16.1 +/- 0.3) and PostPeak (23.5 +/- 0.3 vs. 21.7 +/- 0.2). The rate-of-daily
      change was greater (P < 0.01) in primiparous than in multiparous cows from d-2 to
      5 (+0.2 +/- 0.03 vs. -0.1 +/- 0.02) and from d5 to 10 (+1.2 +/- 0.05 vs. +0.9 +/-
      0.03), but lesser (P < 0.01) from d14 to PostPeak (+0.9 +/- 0.09 vs. +1.3 +/-
      0.06). In primiparous cows, mP4 in PREG was greater at d10 and PostPeak than OPEN
      (11.1 +/- 0.5 and 24.2 +/- 0.5 vs. 9.6 +/- 0.4 and 22.3 +/- 0.4, respectively, P
      < 0.04), but lesser at d5 than P-LOSS (4.4 +/- 0.3 vs. 5.7 +/- 0.4, P = 0.04). In
      multiparous cows, mP4 at d-2 was lesser in PREG than OPEN and P-LOSS (3.2 +/- 0.1
      vs. 3.4 +/- 0.04 and 3.5 +/- 0.1, respectively, P <= 0.03), but greater at d10,
      d14 and PostPeak in PREG than in OPEN (8.2 +/- 0.4, 16.8 +/- 0.5 and 22.7 +/- 0.4
      vs. 6.9 +/- 0.3, 14.8 +/- 0.3 and 19.7 +/- 0.2, respectively, P < 0.01).
      Multiparous PREG cows had greater rate-of-daily-change in mP4 than OPEN cows from
      d5 to 10 and from d10 to 14 (+1.0 +/- 0.06 and +2.2 +/- 0.11 vs. +0.8 +/- 0.04
      and +1.9 +/- 0.08, respectively, P < 0.03). Overall post-AI mP4 increased faster
      and were greater in primiparous than in multiparous cows. Based on in-line mP4
      profiles, greater mP4 levels near time of AI (d-2 in multiparous and d5 in
      primiparous cows) and lesser mP4 beyond d10 were negatively associated with a
      successful pregnancy.

PMID- 28759838
TI  - Finite element analysis of mechanical behavior, permeability and fluid induced
      wall shear stress of high porosity scaffolds with gyroid and lattice-based
      architectures.
AB  - Scaffold design necessitates the consideration of mechanical properties and fluid
      flow dynamics as the main factors in the development of such materials. The
      mechanical behavior of bone scaffolds is characterized by properties such as
      elastic modulus and compressive strength. In terms of fluid flow dynamics, within
      bone scaffolds, permeability is an important parameter that affects cells'
      biological activities, and flow-induced shear stress is used as a mechanical
      stimulant of cell growth. In this study, two scaffold architectures with gyroid
      and lattice-based rectangular unit cells were designed to analysis the effective
      elastic moduli, compressive strength, permeability and fluid flow-induced wall
      shear stress as functions of porosity. Six levels of porosity (65%, 70%, 75%,
      80%, 85% and 90%) were assigned to the scaffold architectures, and 12 models were
      developed. Scaffold deformation under static loading, compressive strength based
      on von Mises criteria, pressure drop, and fluid flow-induced wall shear stress in
      the scaffolds were then determined by finite element analysis. In both the
      scaffold types, models with higher porosity exhibited lower mechanical
      properties. Under the same porosity, the lattice-based scaffolds exhibited a
      Young's modulus and a compressive strength higher than those achieved by the
      gyroid scaffolds. With reference to geometrical parameters and the derived
      pressure drop from the computational fluid dynamics (CFD) analysis, scaffolds
      permeability was calculated using Darcy's law. In both the scaffold
      architectures, high porosity increased permeability and decreased wall shear
      stress. In the same porosity, the lattice-based models exhibited higher
      permeability and lower wall shear stress than did the gyroid models. On the basis
      of the results on elastic modulus and permeability, the models that most
      effectively mimic the properties of cancellous bones were identified.

PMID- 28759839
TI  - Characterization of the bone-metal implant interface by Digital Volume
      Correlation of in-situ loading using neutron tomography.
AB  - Metallic implants are commonly used as surgical treatments for many orthopedic
      conditions. The long-term stability of implants relies on an adequate integration
      with the surrounding bone. Unsuccessful integration could lead to implant
      loosening. By combining mechanical loading with high-resolution 3D imaging
      methods, followed by image analysis such as Digital Volume Correlation (DVC), we
      aim at evaluating ex vivo the mechanical resistance of newly formed bone at the
      interface. X-rays tomography is commonly used to image bone but induces artefacts
      close to metallic components. Utilizing a different interaction with matter,
      neutron tomography is a promising alternative but has not yet been used in
      studies of bone mechanics. This work demonstrates that neutron tomography during
      in situ loading is a feasible tool to characterize the mechanical response of
      bone-implant interfaces, especially when combined with DVC. Experiments were
      performed where metal screws were implanted in rat tibiae during 4 weeks. The
      screws were pulled-out while the samples were sequentially imaged in situ with
      neutron tomography. The images were analyzed to quantify bone ingrowth around the
      implants. DVC was used to track the internal displacements and calculate the
      strain fields in the bone during loading. The neutron images were free of metal
      related artefacts, which enabled accurate quantification of bone ingrowth on the
      screw (ranging from 60% to 71%). DVC allowed successful identification of the
      deformation and cracks that occurred during mechanical loading and led to final
      failure of the bone-implant interface.

PMID- 28759840
TI  - An experimental canine patent ductus arteriosus occlusion device based on shape
      memory polymer foam in a nitinol cage.
AB  - Patent ductus arteriosus (PDA) is a congenital cardiovascular defect in which a
      fetal connection between the aorta and pulmonary artery does not spontaneously
      close shortly after birth. If left uncorrected serious complications and even
      death can occur. Surgical ligation is the traditional treatment method; however,
      it is an invasive procedure, that motivates development of a minimally invasive
      option. Shape memory polymer (SMP) foams are unique materials that hold promise
      in the field of minimally invasive occlusion devices. In this work, a prototype
      nitinol foam cage (NFC) incorporating SMP foams has been designed and evaluated
      in multiple mechanical and in vitro verification tests. The NFC demonstrated
      acceptable fatigue resistance in a preliminary strut integrity test, withstanding
      one million cycles without complete strut fracture. Radial force analysis of both
      thick- and thin-walled prototype variations generated less vessel distension and
      wall tension in a vessel mimic compared to a commercial device. The NFCs
      exhibited negligible in vitro migration, comparable to that of a commercial
      device, using simplified, ideal models of PDA. Deployment characteristics of the
      prototypes were evaluated and compared to that of a commercial device when
      delivered into physiological models of PDA. During mock deployments, a veterinary
      cardiologist noted that, while deliverable, the thin-walled NFC prototype
      exhibited poor deployment characteristics, however the thick-walled NFC had
      deployment characteristics comparable to that of a commercial device. The
      promising results of this study warrant further investigation of the NFC device
      for canine PDA closure.

PMID- 28759841
TI  - A fast and sensitive LC-MS/MS method for the quantification of fosfomycin in
      human urine and plasma using one sample preparation method and HILIC
      chromatography.
AB  - Fosfomycin is an old antibiotic that is increasingly prescribed because of
      emergence of the antibiotic resistance and the growing incidence of multi-drug
      resistant infections. Surprisingly, little is known about its pharmacokinetics
      (PK) and the pharmacodynamics (PD). Quantification of fosfomycin in both urine
      and plasma provides insight into the PK/PD characteristics of fosfomycin, which
      is crucial for the optimization of the therapy and the prevention of the
      emergence of resistance. An analytical method is therefore needed for the
      quantification of fosfomycin in both urine and plasma. A fast and sensitive
      tandem mass spectrometry method in combination with HILIC chromatography for the
      quantification of fosfomycin with a universal sample preparation method for urine
      and plasma was developed and validated according to FDA guidelines. The universal
      sample preparation method only requires 100MUL of a sample, the addition of the
      internal standard fosfomycin-13C3 benzylamine and an ultrafiltration step. The
      method is applicable for the concentration range of 0.75-375mg/L (R2 of 0.9998 in
      both matrices) encompassing the clinically relevant concentration range based on
      the susceptibility of possible (uro)pathogens in the clinical setting. The
      validation results for urine and plasma for all QC levels, were <2.1% and <3.2%
      for accuracy, <1.5% and <1.7% for within day precision and <5.0% and <3.8% for
      between day precision, respectively. No matrix effects were encountered and the
      total recovery in urine and plasma was high (102.5% and 99.4%). Prepared samples
      were stable at 4 degrees C and 15 degrees C for at least 72h and stored samples
      at -80 degrees C were stable for at least 6 months. Selectivity and sensitivity
      were confirmed and no carry-over was observed. The method was successfully
      applied in two pharmacokinetic studies in healthy volunteers and patients
      respectively.

PMID- 28759842
TI  - Determination of vitacoxib, a novel COX-2 inhibitor, in equine plasma using UPLC
      MS/MS detection: Development and validation of new methodology.
AB  - Vitacoxib is an imidazole derivative and the novel COX-2 selective inhibitor to
      be marketed for veterinary use as nonsteroidal anti-inflammatory drugs. No
      analytical assay to quantify vitacoxib in equine plasma samples has been
      published to date. In the current study, we aim to develop and validate a brief,
      quick and sensitive UPLC-MS/MS method for quantification of vitacoxib in equine
      plasma samples. Plasma samples were precipitated with methyl tert-butyl ether.
      The Phenomenex column (Kinetex 50*2.1mm i.d. particle size=2.6MUm, C18, 100A) at
      25 degrees C was used in chromatographic separation with mobile phase consisting
      of acetonitrile and water (containing 0.1% formic acid) at flow rate of
      0.4mL/min. Vitacoxib and internal standard (IS, celecoxib) were detected under
      the multiple-reaction monitoring mode by mass spectrometer with ESI+ (m/z
      347.9/269.03 for vitacoxib and m/z 382.0/362.0 for IS, respectively). The curve
      concentration range of was 0.5-500ng/mL with a lower limit of quantification
      0.5ng/mL (r2=0.996309) in equine plasma samples. The selectivity, precision,
      recovery, accuracy, matrix effect and stability under various conditions were
      conformed to the acceptance requirements. Pharmacokinetic studies of vitacoxib in
      horses via oral administration (0.1mg/kg) demonstrated that the procedure was
      fully validated and successfully. A meaningful basis for assessing the vitacoxib
      or clinical applications of vitacoxib to horse is provided in the present study.

PMID- 28759843
TI  - TRIM28 epigenetic corepressor is indispensable for stable induced pluripotent
      stem cell formation.
AB  - Cellular reprogramming proceeds in a stepwise pathway initiated by binding and
      transcription of pluripotency factors followed by genome-wide epigenetic changes.
      Priming events, such as erasure of DNA methylation and chromatin remodeling
      determines the success of pluripotency acquisition later. Therefore, growing
      efforts are made to understand epigenetic regulatory network that makes
      reprogramming possible and efficient. Here, we analyze the role of
      transcriptional corepressor TRIM28, involved in heterochromatin formation, during
      the process of reprogramming of mouse somatic cells into induced pluripotent stem
      cells (iPS cells). We demonstrate that Trim28 knockdown (Trim28 KD) causes that
      emerging iPS cells differentiate immediately back into MEFs therefore they fail
      to yield stable iPS cell colonies. To better comprehend the mechanism of TRIM28
      action in reprogramming, we performed a reverse-phase protein array (RPPA) using
      in excess of 300 different antibodies and compared the proteomic profiles of wild
      type and Trim28 KD cells during reprogramming. We revealed the differences in the
      dynamics of reprogramming of wild-type and Trim28 KD cells. Interestingly,
      proteomic profile of Trim28 KD cells at the final stage of reprogramming
      resembled differentiated state rather than maintenance of pluripotency and self
      renewal, strongly suggesting spontaneous differentiation of Trim28 KD cells back
      to their parental cell type. We also observed that action of TRIM28 in
      reprogramming is accompanied by differential enrichment of proteins involved in
      cell cycle, adhesion and stemness. Collectively, these results suggest that
      regulation of epigenetic modifications coordinated by TRIM28 plays a crucial role
      in reprogramming process.

PMID- 28759844
TI  - Circulating soluble receptor for advanced glycation end product: Cross-sectional
      associations with cardiac markers and subclinical vascular disease in older men
      with and without diabetes.
AB  - BACKGROUND AND AIMS: The soluble receptor for advanced glycation end products
      (sRAGE) has been implicated in diabetic vascular complications. We have examined
      the association between sRAGE and cardiac markers [NT-proBNP and cardiac troponin
      T (cTnT)] and subclinical vascular markers in older men with and without
      diabetes. METHODS: We performed a cross-sectional study of 1159 men aged 71-92
      years with no history of cardiovascular disease (myocardial infarction, stroke,
      heart failure, coronary artery bypass graft operation or angioplasty). Prevalent
      diabetes included men with a doctor diagnosis of diabetes, men with fasting
      glucose >=7 mmol/l or HbA1c >= 6.5% (N = 180). Subclinical vascular measurements
      included carotid intima media thickness (cIMT), arterial stiffness [pulse wave
      velocity (PWV)], central aortic blood pressure and arterial wave reflections
      [central augmentation pressure (AP) and augmentation index (AIx)]. RESULTS: sRAGE
      was strongly and positively associated with renal dysfunction in men with and
      without diabetes. sRAGE was significantly and positively associated with NT
      proBNP (but not cTnT) and AP and AIx in both groups of men after adjustment for
      CVD risk and metabolic risk markers, renal function and inflammation. However, no
      association was seen between sRAGE and central aortic blood pressure, cIMT or
      arterial stiffness as determined by PWV in either group. CONCLUSIONS: Higher
      plasma sRAGE was associated with increased NT-proBNP and markers of arterial wave
      reflections in men both with and without diabetes. Increased sRAGE may contribute
      to or be a marker of worsening cardiac dysfunction or HF. Further studies with
      cardiac imaging data are required to confirm this.

PMID- 28759846
TI  - The association of folate and depression: A meta-analysis.
AB  - BACKGROUND: Previous research suggested that folate levels play an important role
      in the etiology and course of depression. However, the literature has been
      inconsistent with regard to differences in folate level between individuals with
      and without depression. The present meta-analysis synthesized the results of
      previous studies to examine whether individuals with depression had lower levels
      of folate than individuals without depression. METHODS: Meta-analytic procedures
      were conducted in accordance with PRISMA guidelines. Studies evaluating folate
      levels in individuals with and without depression via red blood cell folate,
      serum folate, or dietary intake of folate methods were identified via PsycINFO
      and PubMed. Random-effects meta-analysis was conducted using Hedge's g, and
      moderation analysis was used for both folate measurement method and population
      type. Study heterogeneity was assessed with I2 and publication bias was
      qualitatively assessed via funnel plot and quantitatively assessed with the trim
      and-fill method and Begg's adjusted rank test. RESULTS: We found a significant,
      small effect size, such that individuals with depression had lower folate levels
      than those without depression, Hedge's g = -0.24 (95% CI = -0.31, -0.16), p <
      0.001. Study heterogeneity was high (I2 = 84.88%), and neither folate measurement
      method nor population accounted for study heterogeneity. CONCLUSIONS: Individuals
      with depression have lower serum levels of folate and dietary folate intake than
      individuals without depression. Given that previous literature suggested folate
      supplementation improved the efficacy of traditional antidepressant medications,
      future research on folate supplementation in depression is warranted and
      clinicians may wish to consider folate supplementation for patients with
      depression.

PMID- 28759847
TI  - Photosynthetic properties of spring geophytes assessed by chlorophyll
      fluorescence analysis.
AB  - Since spring ephemerals are credited to be all "sun" species with unusually
      elevate photosynthesis, in contrast to shade-tolerant trees and understory
      geophytes with a long aboveground cycle, we examined the photosynthetic
      efficiency of 6 woody species, 9 long-cycle geophytes, and 8 spring ephemeral
      geophytes using blue flashes of increasing energy with the Imaging PAM
      fluorometer. Several parameters were obtained: quantum yield of electron
      transport (PhiETR) or of PSII (PhiPSII), maximum measured photosynthesis rate
      (ETRhv), maximum extrapolated rate of photosynthesis (ETRem), half-saturating
      photon flux density (KPAR), and in some cases photochemical (qP) and non
      photochemical quenching (NPQ). Results confirm the ecological consistency of the
      three plant groups, with internal differences. Woody species have low ETRem and
      KPAR values with good PhiETR; long-cycle herbs have low ETRem and PhiETR and
      moderate KPAR values; spring ephemerals have elevate PhiETR, ETRem and KPAR
      values. The mean ETRem of ephemerals of 91 MUmol m-2 s-1 exceeds that of long
      cycle herbs 2.9-fold and woody species 4.8-fold, and corresponds to 19 MUmol CO2
      m-2 s-1 by assuming an ETR/PhiCO2 ratio of 4.7. Highest photosynthesis rates and
      KPAR were exhibited by five ephemerals (Eranthis, Erythronium, Narcissus, Scilla,
      Tulipa) with peak ETRem values equivalent to ~40 MUmol CO2 m-2 s-1 or ~60 MUmol
      CO2 (g Chl)-1 s-1 ("sun" species). According to a new, fluorescence based
      heliophily index, all trees and five long-cycle herbs were definitely "shade"
      species, while four long-cycle herbs and three ephemerals were intermediate shade
      tolerant.

PMID- 28759845
TI  - A comprehensive model of predictors of persistence and recurrence in adults with
      major depression: Results from a national 3-year prospective study.
AB  - Identifying predictors of persistence and recurrence of depression in individuals
      with a major depressive episode (MDE) poses a critical challenge for clinicians
      and researchers. We develop using a nationally representative sample, the
      National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N =
      34,653), a comprehensive model of the 3-year risk of persistence and recurrence
      in individuals with MDE at baseline. We used structural equation modeling to
      examine simultaneously the effects of four broad groups of clinical factors on
      the risk of MDE persistence and recurrence: 1) severity of depressive illness, 2)
      severity of mental and physical comorbidity, 3) sociodemographic characteristics
      and 4) treatment-seeking behavior. Approximately 16% and 21% of the 2587
      participants with an MDE at baseline had a persistent MDE and a new MDE during
      the 3-year follow-up period, respectively. Most independent predictors were
      common for both persistence and recurrence and included markers for the severity
      of the depressive illness at baseline (as measured by higher levels on the
      general depressive symptom dimension, lower mental component summary scores,
      prior suicide attempts, younger age at onset of depression and greater number of
      MDEs), the severity of comorbidities (as measured by higher levels on dimensions
      of psychopathology and lower physical component summary scores) and a failure to
      seek treatment for MDE at baseline. This population-based model highlights
      strategies that may improve the course of MDE, including the need to develop
      interventions that target multiple psychiatric disorders and promotion of
      treatment seeking to increase access to timely mental health care.

PMID- 28759848
TI  - 2DCOS and PCMW2D analysis of FT-IR/ATR spectra measured at variable temperatures
      on-line to a polyurethane polymerization.
AB  - In the present communication the potential of 2DCOS analysis and the spin-off
      technique perturbation-correlation moving window 2D (PCMW2D) analysis is
      illustrated with reference to spectroscopic changes observed in a data set
      recorded by in-line fiber-coupled FT-IR spectroscopy in the attenuated total
      reflection (ATR) mode during a polyurethane solution polymerization at different
      temperatures. In view of the chemical functionalities involved, hydrogen bonding
      plays an important role in this polymerization reaction. Based on the 2DCOS and
      PCMW2D analysis, the sequence of hydrogen bonding changes accompanying the
      progress of polymerization and precipitation of solid polymer can be determined.
      Complementary to the kinetic data derived from the original variable-temperature
      spectra in a previous publication the results provide a more detailed picture of
      the investigated solution polymerization.

PMID- 28759849
TI  - Mercaptosuccinic acid-coated NIR-emitting gold nanoparticles for the sensitive
      and selective detection of Hg2.
AB  - A sensitive fluorescent detection platform for Hg2+ was constructed based on
      mercaptosuccinic acid (MSA) coated near-infrared (NIR)-emitting gold
      nanoparticles (AuNPs). The thiolated mercaptosuccinic acid was employed as both
      reducing agent and surface coating ligand in a one-step synthesis of NIR-emitting
      AuNPs (MSA-AuNPs), which exhibited stable fluorescence with the maximum
      wavelength at 800nm and a wide range of excitation (220-650nm) with the maxima at
      413nm. The MSA coated NIR-emitting AuNPs showed a rapid fluorescence quenching
      toward Hg2+ over other metal ions with a limit of detection (LOD, 3delta) as low
      as 4.8nM. The sensing mechanism investigation revealed that the AuNPs formed
      aggregation due to the "recognition" of Hg2+ from the MSA, and the resultant
      strong coupling interaction between Hg2+ and Au (I) to further quench the
      fluorescence of the AuNPs, which synergistically resulted in a highly sensitive
      and selective fluorescence response toward Hg2+. This proposed strategy was also
      demonstrated the possibility to be used for Hg2+ detection in water samples.

PMID- 28759850
TI  - Structural and spectroscopic study of arsenate and vanadate incorporation into
      apatite group: Implications for semi-quantitative estimation of As and V contents
      in apatite.
AB  - The solid solutions of mimetite-vanadinite series were synthesized at room
      temperature through aqueous precipitation method and were characterized with
      Scanning Electron Microscope-Energy Dispersive Spectrometer (SEM-EDS), X-ray
      diffraction (XRD), infrared and Raman spectroscopy. Based on the XRD analyses, it
      showed that all the samples crystallize with the same structure. A and c
      parameters vary smoothly with substitution of AsO43- for VO43-. In the FT-IR
      spectra of mimetite-vanadinite solid solutions series, the bands corresponding to
      stretching (v3) vibrations of AsO43- and VO43- ions were observed in the range
      700-900cm-1, and the bending (v4) vibrations of OAsO and OVO were observed in the
      range 310-400cm-1. In the Raman spectra, the bands attributed to vibrations in
      the VO43- appeared at 830-700cm-1, 420-290cm-1. The bands attributed to
      vibrations in the AsO43- appeared in the ranges 740-820cm-1, 410-310cm-1. In
      addition, the peak positions of the dominant antisymmetric stretching (v3) of VO
      bond around 706cm-1 of IR spectra for the prepared solids also varies with the
      different As/(As+V) ratio, and the relationship is linear, which can be an
      implication for semi-quantitative estimation of As and V contents in lead
      apatites.

PMID- 28759851
TI  - Relationship of carbohydrates and lignin molecular structure spectral profiles to
      nutrient profile in newly developed oats cultivars and barley grain.
AB  - The objectives of this study were to quantify the chemical profile and the
      magnitude of differences in the oat and barley grain varieties developed by Crop
      Development Centre (CDC) in terms of Cornell Net Carbohydrate Protein System
      (CNCPS) carbohydrate sub-fractions: CA4 (sugars), CB1 (starch), CB2 (soluble
      fibre), CB3 (available neutral detergent fibre - NDF), and CC (unavailable
      carbohydrate); to estimate the energy values; to detect the lignin and
      carbohydrate (CHO) molecular structure profiles in CDC Nasser and CDC Seabiscuit
      oat and CDC Meredith barley grains by using Fourier transform infrared attenuated
      total reflectance (FTIR-ATR); to develop a model to predict nutrient supply based
      on CHO molecular profile. Results showed that NDF, ADF and CHO were greater
      (P<0.05) in oat than in barley. The starch content was greater (P<0.05) in barley
      than in oat. The CDC Meredith showed greater total rumen degradable carbohydrate
      (RDC), intestinal digestible fraction carbohydrate (FC) and lower total rumen
      undegradable carbohydrate (RUC). However, the estimated milk production did not
      differ for CDC Nasser oat and CDC Meredith barley. Lignin peak area and peak
      height did not differ (P>0.05) for oat and barley grains as well as non
      structural CHO. However, cellulosic compounds peak area and height were greater
      (P<0.05) in oat than barley grains. Multiple regressions were determined to
      predict nutrient supply by using lignin and CHO molecular profiles. It was
      concluded that although there were some differences between oat and barley
      grains, CDC Nasser and CDC Meredith presented similarities related to chemical
      and molecular profiles, indicating that CDC Meredith barley could be replaced for
      CDC Nasser as ruminant feed. The FTIR was able to identify functional groups
      related to CHO molecular spectral in oat and barley grains and FTIR-ATR results
      could be used to predict nutrient supply in ruminant livestock systems.

PMID- 28759852
TI  - The role of different network modifying cations on the speciation of the Co2+
      complex in silicates and implication in the investigation of historical glasses.
AB  - In the last decades the speciation of the cobalt complex in a glass matrix has
      been extensively studied. Bivalent cobalt ions in glasses of different
      composition commonly adopt a tetrahedral coordination, though hexa- or penta
      coordinated species are also possible. Changes in the absorbance spectrum of Co
      doped glasses were attested in previous studies according to the introduction of
      different modifying cations. A shifting of the first sub-band characterizing the
      typical triplets of tetrahedral Co2+ ions in both the visible and near infrared
      regions was observed, but discrepancies in literature suggested a relevant role
      of glass composition on the definition of the optical signature of cobalt. Co
      doped glasses with different composition (soda-lime, potash-lime, mixed alkali
      and ZnO-Na2O-CaO-SiO2) were studied via Fiber Optic Reflectance Spectroscopy
      (FORS). Pseudo-Voigt functions were used for the deconvolution of the absorbance
      spectra and the features of the bands characteristic of each cobalt complex were
      investigated. The structural role played by each modifying cation and the
      fundamental implications of glass basicity on the speciation of different Co
      complexes were stressed. Changes in glass structure resulted in different
      equilibria between the three absorbing species whose specific optical signatures
      in the 480-530nm region interact to determine the resulting absorbance spectrum.

PMID- 28759853
TI  - Spectroscopic studies of Dy3+ ion doped tellurite glasses for solid state lasers
      and white LEDs.
AB  - Rare earth ion Dy3+-doped tellurite glasses were synthesised in the system of (75
      x)TeO2-15Sb2O3-10WO3-xDy2O3 (TSWD glasses). XRD and FTIR characterizations were
      used to find the crystalline and structural properties. The intensities of the
      electronic transitions and the ligand environment around the Dy3+ ion were
      determined using the Judd-Ofelt (J-O) theory on the absorption spectra of the
      glasses. The measured luminescence spectra exhibit intense emissions at 574 and
      484nm along with less intense emissions around 662 and 751nm. Various radiative
      properties of the 4F9/2 excited level of Dy3+ ion were calculated for the
      glasses. Decay profiles were measured to find the life times and quantum
      efficiencies. Yellow to blue intensity ratio (Y/B), CIE chromaticity coordinates
      and correlated color temperature (CCT) values are calculated using the emission
      spectra to evaluate the emitted light. The obtained results suggest the utility
      of the glasses for potential yellow laser and white LED's applications.

PMID- 28759854
TI  - Analytical method development and validation of spectrofluorimetric and
      spectrophotometric determination of some antimicrobial drugs in their
      pharmaceuticals.
AB  - In this study, three novel, sensitive, simple and validated spectrophotometric
      and spectrofluorimetric methods have been proposed for estimation of some
      important antimicrobial drugs. The first two methods have been proposed for
      estimation of two important third-generation cephalosporin antibiotics namely,
      cefixime and cefdinir. Both methods were based on condensation of the primary
      amino group of the studied drugs with acetyl acetone and formaldehyde in acidic
      medium. The resulting products were measured by spectrophotometric (Method I) and
      spectrofluorimetric (Method II) tools. Regarding method I, the absorbance was
      measured at 315nm and 403nm with linearity ranges of 5.0-140.0 and 10.0
      100.0MUg/mL for cefixime and cefdinir, respectively. Meanwhile in method II, the
      produced fluorophore was measured at lambdaem 488nm or 491nm after excitation at
      lambdaex 410nm with linearity ranges of 0.20-10.0 and 0.20-36.0MUg/mL for
      cefixime and cefdinir, respectively. On the other hand, method III was devoted to
      estimate nifuroxazide spectrofluorimetrically depending on formation of highly
      fluorescent product upon reduction of the studied drug with Zinc powder in acidic
      medium. Measurement of the fluorescent product was carried out at lambdaem 335nm
      following excitation at lambdaex 255nm with linearity range of 0.05 to 1.6MUg/mL.
      The developed methods were subjected to detailed validation procedure, moreover
      they were used for the estimation of the concerned drugs in their
      pharmaceuticals. It was found that there is a good agreement between the obtained
      results and those obtained by the reported methods.

PMID- 28759855
TI  - Computational investigations of trans-platinum(II) oxime complexes used as
      anticancer drug.
AB  - Some platinum oxime complexes are optimized at HF/CEP-31G level which has been
      reported as the best level for these type complexes in the gas phase. IR spectrum
      is calculated and the new scale factor is derived. NMR spectrum is calculated at
      the same level of theory and examined in detail. Quantum chemical parameters
      which have been mainly used are investigated and their formulas are given in
      detail. Additionally, selected quantum chemical parameters of studied complexes
      are calculated. New theoretical IC50% formulas are derived and biological
      activity rankings of mentioned complexes are investigated.

PMID- 28759856
TI  - High-flux ultrafiltration membrane based on electrospun polyacrylonitrile
      nanofibrous scaffolds for arsenate removal from aqueous solutions.
AB  - Arsenic contamination in drinking water is a serious problem worldwide. In this
      study, to remove arsenate from contaminated water, a new thin-film composite
      (TFC) membrane was fabricated and tested. This membrane was composed of an
      electrospun nanofibrous scaffold, a polyethylene terephthalate (PET) substrate as
      support, and a polyacrylonitrile (PAN) coating layer. To effectively reject
      arsenate ions, cetylpyridinium chloride (CPC) pretreatment was used. For
      evaluating the performance of TFC membrane, its flux and contaminant rejection
      were compared to a conventional ultrafiltration (UF) membrane. Due to high
      porosity, the TFC membrane showed a flux, which was 172-520% higher than the UF
      membrane. In addition, The TFC membrane was 1.1-1.3 times more efficient in
      rejecting arsenate ions than the UF membrane.

PMID- 28759857
TI  - Comparative study on polyvinyl chloride film as flexible substrate for preparing
      free-standing polyaniline-based composite electrodes for supercapacitors.
AB  - The free-standing polyaniline (PANI)-based composite film electrodes were
      prepared with polyvinyl chloride (PVC) and the aniline modified PVC (PVC-An)
      films as flexible substrates for supercapacitors, via facile in-situ chemical
      oxidative polymerization of aniline, with conventional chemical oxidative
      polymerization or rapid-mixing chemical oxidative polymerization technique. Owing
      to the grafting of PANI from the PVC-An film as substrate and the suppression of
      the secondary growth of the primary PANI particles in the rapid-mixing chemical
      oxidative polymerization, the PVC-g-PANI-2 composite film with loose surface
      possessed better comprehensive performance, accompanying the high specific
      capacitance (645.3F/g at a current density of 1A/g), good rate capacitance
      (retaining 63.2% of original value at a current density of 10A/g and 52.0% at a
      scan rate of 100mV/s), good cycle stability (retaining 83.1% after 1000 cycles)
      and the improved internal resistance. Besides its excellent flexibility, it could
      retain 61.2% of its original specific capacitance under the stress of 8.66MPa for
      1h, demonstrating a good tensile-resistance.

PMID- 28759858
TI  - Expansion of Kolarik model for tensile strength of polymer particulate
      nanocomposites as a function of matrix, nanoparticles and interphase properties.
AB  - Kolarik proposed a model for tensile strength of polymer particulate composites
      based on the cubic orthogonal skeleton or three perpendicular plates (3PP)
      system. In this paper, Kolarik model is expanded for tensile strength of polymer
      nanocomposites containing spherical nanoparticles assuming the interphase
      properties. This model expresses the strength as a function of interphase
      properties. This development is performed using some models such as Pukanszky and
      Nicolais-Narkis. The expanded model is applied to calculate the thickness and
      strength of interphase by the experimental results. Furthermore, the strength of
      polymer nanocomposites is evaluated at different levels of material and
      interphase properties. The experimental data show good agreement with the
      predictions of the developed model.

PMID- 28759859
TI  - Temperature-responsive nanogel multilayers of poly(N-vinylcaprolactam) for
      topical drug delivery.
AB  - We report nanothin temperature-responsive hydrogel films of poly(N
      vinylcaprolactam) nanoparticles (nuPVCL) with remarkably high loading capacity
      for topical drug delivery. Highly swollen (nuPVCL)n multilayer hydrogels, where n
      denotes the number of nanoparticle layers, are produced by layer-by-layer
      hydrogen-bonded assembly of core-shell PVCL-co-acrylic acid nanoparticles with
      linear PVPON followed by cross-linking of the acrylic acid shell with either
      ethylene diamine (EDA) or adipic acid dihydrazide (AAD). We demonstrate that a
      (nuPVCL)5 film undergoes dramatic and reversible swelling up to 9 times its dry
      thickness at pH = 7.5, indicating 89v/v % of water inside the network. These
      hydrogels exhibit highly reversible ~3-fold thickness changes with temperature
      variations from 25 to 50 degrees C at pH = 5, the average pH of human skin. We
      also show that a (nuPVCL)30 hydrogel loaded with ~120ugcm-2 sodium diclofenac, a
      non-steroidal anti-inflammatory drug used for osteoarthritis pain management,
      provides sustained permeation of this drug through an artificial skin membrane
      for up to 24h at 32 degrees C (the average human skin surface temperature). The
      cumulative amount of diclofenac transported at 32 degrees C from the (nuPVCL)30
      hydrogel after 24h is 12 times higher than that from the (nuPVCL)30 hydrogel at
      22 degrees C. Finally, we demonstrate that the (nuPVCL) hydrogels can be used for
      multiple drug delivery by inclusion of Nile red, fluorescein and DAPI dyes within
      the nuPVCL nanoparticles prior to hydrogel assembly. Using confocal microscopy we
      observed the presence of separate dye-loaded nuPVCL compartments within the
      hydrogel matrix with all three dyes confined to the nanogel particles without
      intermixing between the dyes. Our study provides opportunity for development of
      temperature-responsive multilayer hydrogel coatings made via the assembly of core
      shell nanogel particles which can be used for skin-sensitive materials for
      topical drug delivery.

PMID- 28759860
TI  - Super-hydrophobic coatings based on non-solvent induced phase separation during
      electro-spraying.
AB  - HYPOTHESIS: The polymer solution concentration determines whether electrospinning
      or electro-spraying occurs, while the addition of the non-solvent into the
      polymer solution strongly influences the surface morphology of the obtained
      products. Both smooth and porous surfaces of the electro-sprayed microspheres can
      be harvested by choosing different non-solvent and its amount as well as
      incorporating polymeric additives. EXPERIMENTS: The influences of the solution
      concentration, weight ratio between the non-solvent and the copolymer, and the
      polymeric additives on the surface morphology and the wettability of the electro
      sprayed products were systematically studied. FINDINGS: Surface pores and/or
      asperities on the microsphere surface were mainly caused by the non-solvent
      induced phase separation (NIPS) and subsequent evaporation of the non-solvent
      during electro-spraying. With increasing polymer solution concentration, the
      microsphere was gradually changed to the bead-on-string geometry and finally to a
      nanofiber form, leading to a sustained decrease of the contact angle (CA). It was
      found that the substrate coatings derived from the microspheres possessing
      hierarchical surface pores or dense asperities had high surface roughness and
      super-hydrophobicity with CAs larger than 150 degrees  while sliding angles
      smaller than 10 degrees ; but coatings composed of microspheres with smooth
      surfaces gave relatively low CAs.

PMID- 28759861
TI  - Concurrent hyperadrenocorticism and diabetes mellitus in dogs.
AB  - Hyperadrenocorticism (HAC) and diabetes mellitus (DM) are two diseases that can
      occur concurrently in dogs. The objective of this study was to evaluate the
      coexistence of HAC and DM, and the risk factors involved that could contribute to
      the development of DM in dogs with HAC. A total of 235 dogs with HAC were studied
      and, according to their fasting glycemia, they were divided into three groups:
      <5.6mmol/L, between 5.6 and 10.08mmol/L and >10.08mmol/L. The following
      parameters were evaluated: age, gender, cause of HAC, body condition, glycemia,
      total cholesterol, triglycerides, urinary cortisol:creatinin ratio (UCCR) and
      survival time. A 13.61% concurrence of HAC and DM was observed. Dogs with a
      fasting glycemia >5.6mmol/L, with dislipemia, with Pituitary-Dependent
      Hyperadrenocorticism, UCCR >100*10-6 and non-castrated females showed a higher
      risk of developing DM. The development of DM in dogs with HAC reduces the
      survival time.

PMID- 28759862
TI  - Genetic diversity in envelope genes of contemporary U.S. porcine reproductive and
      respiratory syndrome virus strains influences viral antigenicity.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is one of the most
      economically important diseases in swine caused by porcine reproductive and
      respiratory syndrome virus (PRRSV). Genome sequences of sixty-six PRRSV strains
      were obtained using metagenomic sequencing of serum samples collected in the U.S.
      in 2014 to explore contemporary genetic diversity. Phylogenetic analysis of the
      genes encoding the envelope proteins identified four to eight distinct lineages
      with >87% intraclade identity. To explore the effect of the observed genetic
      diversity on antigenicity, the genome regions encoding either GP2a-GP3-GP4 or GP5
      M in strain SD95-21 were replaced with alleles from each of eight distinct PRRSV
      strains using reverse genetics. The GP2a-GP3-GP4 region from only four of the
      eight strains yielded viable recombinant virus. When viable, both GP2a-GP3-GP4
      and GP5-M variably affected antigenicity. A strain-dependent significant loss in
      cross reactivity was variably observed by indirect immunofluorescence assays
      using antisera from pigs vaccinated with commercial modified-live vaccines
      following replacement of GP2a-GP3-GP4 or GP5-M. Significantly reduced
      neutralization titers were similarly measured using antisera from naturally PRRSV
      exposed pigs. These results illustrate the need to consider genomic regions
      besides GP5 for PRRSV epidemiology and vaccination.

PMID- 28759863
TI  - Lyophilic matrix method for dissolution and release studies of nanoscale
      particles.
AB  - We introduce a system with a lyophilic matrix to aid dissolution studies of
      powders and particulate systems. This lyophilic matrix method (LM method) is
      based on the ability to discriminate between non-dissolved particles and the
      dissolved species. In the LM method the test substance is embedded in a thin
      lyophilic core-shell matrix. This permits rapid contact with the dissolution
      medium while minimizing dispersion of non-dissolved particles without presenting
      a substantial diffusion barrier. The method produces realistic dissolution and
      release results for particulate systems, especially those featuring nanoscale
      particles. By minimizing method-induced effects on the dissolution profile of
      nanopowders, the LM method overcomes shortcomings associated with current
      dissolution tests.

PMID- 28759864
TI  - Characterization of the phase I and phase II metabolic profile of tolvaptan by in
      vitro studies and liquid chromatography-mass spectrometry profiling: Relevance to
      doping control analysis.
AB  - Phase I and phase II biochemical reactions involved in the biotransformation
      pathways of tolvaptan were characterized by LC-MS-based techniques and in vitro
      models to identify the most appropriate marker(s) of intake. The effects of
      physiological and non-physiological factors on the metabolic profile of tolvaptan
      were also evaluated. In vitro approaches were based on the use of pooled human
      liver microsomes and recombinant isoforms of cytochrome P450 and uridine
      diphospho glucuronosyl-transferase. Sample preparation included liquid/liquid
      extraction at neutral pH with tert-butyl methyl-ether. In the case of the study
      of phase II metabolism an additional enzymatic hydrolysis step was performed. The
      chromatographic separation was carried out using reversed-phase chromatography,
      whereas detection was performed by either triple-quadrupole or time-of-flight
      analyzers in positive electrospray ionization and different acquisition modes.
      Our data show that tolvaptan is metabolized to at least 20 phase I metabolites,
      the biotransformation reactions being catalyzed mainly by CYP3A4 and CYP3A5
      isoforms. The phase-I reactions include hydroxylation (in different positions),
      carboxylation, oxidation, hydrogenation, dealkylation, isomerization and a
      combination of the above. Most of the phase I metabolites undergo
      glucuronidation, carried out mostly by UGT2B7 and UGT2B17 isoforms. Dealkylated,
      mono-hydroxylated and carboxylated metabolites both in the free and in the
      glucuronidated form appear to be the most suitable urinary diagnostic markers for
      the detection of tolvaptan intake in doping control. Concerning the effects of
      physiological and non-physiological factors on the metabolic profile of
      tolvaptan, our results show that (i) no significant gender differences were
      detected; (ii) significant differences were registered in the presence of
      different CYP3A5 allelic variants, and finally (iii) a marked reduction of the
      detected metabolites was registered in the presence of antifungals, and, to a
      lesser extent, of steroidal progestins.

PMID- 28759865
TI  - Cognitive bias modification: A review of meta-analyses.
AB  - BACKGROUND: Cognitive bias modification (CBM) is a novel, but controversial
      intervention with considerable divergence amongst conclusions in individual
      studies and reviews. This systematic review synthesizes meta-analyses of CBM to
      determine whether CBM is effective, and what parameters most reliably evoke the
      process of CBM. METHODS: A systematic literature search resulted in twelve meta
      analyses in total, from which the published effect sizes were extracted. RESULTS:
      Attention bias modification (ABM) shifted targeted biases in adults (ES = 0.24
      1.16), was effective as a buffer to stressor vulnerability (ES = 0.33-0.77) and
      in symptom control (ES = 0.16-0.41). Cognitive bias modification for
      interpretation (CBM-I) modified targeted biases (ES = 0.52-0.81) but did not
      reliably reduce stressor vulnerability (ES = 0.01-0.24, p > .05). CBM
      consistently reduced anxiety symptoms, but effects on depressive symptomatology
      were less compelling. The long-term efficacy of CBM was only supported in
      addiction studies. LIMITATIONS: The review included a single CBM-I only meta
      analysis, and two meta-analyses with pooled reporting on ABM and CBM-I outcomes.
      CONCLUSIONS: Overall, this synthesis shows CBM is effective in the short-term for
      anxiety in adults, and highlights some conditions under which CBM is most
      efficacious. Rather than debating the efficacy of CBM, future research should
      focus on developing procedures that more reliably induce bias modification and
      determining the most efficacious clinical applications.

PMID- 28759866
TI  - Oral health impacts of medications used to treat mental illness.
AB  - BACKGROUND: Many psychotropic medications affect oral health. This review
      identified oral side effects for antidepressant, antipsychotic, anticonvulsant,
      antianxiety and sedative drugs that are recommended in Australia for the
      management of common mental illnesses and provides recommendations to manage
      these side-effects. METHODS: The Australian Therapeutic Guidelines and the
      Australian Medicines Handbook were searched for medications used to treat common
      mental health conditions. For each medication, the generic name, class, and drug
      company reported side-effects were extracted from the online Monthly Index of
      Medical Specialties (eMIMs) and UpToDate databases. Meyler's Side Effect of Drugs
      Encyclopaedia was used to identify additional oral adverse reactions to these
      medications. RESULTS: Fifty-seven drugs were identified: 23 antidepressants, 22
      antipsychotics or mood stabilisers, and 12 anxiolytic or sedative medications.
      Xerostomia (91%) the most commonly reported side effect among all classes of
      medications of the 28 identified symptoms. Other commonly reported adverse
      effects included dysguesia (65%) for antidepressants, and tardive dyskinesia
      (94%) or increased salivation (78%) for antipsychotic medications. CONCLUSIONS:
      While xerostomia has often been reported as a common adverse effect of
      psychotropic drugs, this review has identified additional side effects including
      dysguesia from antidepressants and tardive dyskinesia and increased salivation
      from antipsychotics. Clinicians should consider oral consequences of psychotropic
      medication in addition to other side-effects when prescribing. For
      antidepressants, this would mean choosing duloxetine, agomelatine and any of the
      serotonin re-uptake inhibitors except sertraline. In the case of antipsychotics
      and mood stabilisers, atypical agents have less oral side effects than older
      alternatives.

PMID- 28759867
TI  - Fuzzy comprehensive evaluation of multiple environmental factors for swine
      building assessment and control.
AB  - In confined swine buildings, temperature, humidity, and air quality are all
      important for animal health and productivity. However, the current swine building
      environmental control is only based on temperature; and evaluation and control
      methods based on multiple environmental factors are needed. In this paper, fuzzy
      comprehensive evaluation (FCE) theory was adopted for multi-factor assessment of
      environmental quality in two commercial swine buildings using real measurement
      data. An assessment index system and membership functions were established; and
      predetermined weights were given using analytic hierarchy process (AHP) combined
      with knowledge of experts. The results show that multi-factors such as
      temperature, humidity, and concentrations of ammonia (NH3), carbon dioxide (CO2),
      and hydrogen sulfide (H2S) can be successfully integrated in FCE for swine
      building environment assessment. The FCE method has a high correlation
      coefficient of 0.737 compared with the method of single-factor evaluation (SFE).
      The FCE method can significantly increase the sensitivity and perform an
      effective and integrative assessment. It can be used as part of environmental
      controlling and warning systems for swine building environment management to
      improve swine production and welfare.

PMID- 28759868
TI  - An index for the evaluation of 3D masticatory cycles stability.
AB  - OBJECTIVES: To introduce an index (Masticatory Stability Index, MSI) to analyze
      the stability of chewing cycles in standardized conditions and test it in a group
      of patients with subclinical mild temporomandibular disorder (TMD). DESIGN: 23
      subjects with mild subacute TMD and 21 healthy subjects were involved; they all
      responded to a questionnaire about signs and symptoms of TMD (ProTMDmulti) and
      underwent a myofunctional orofacial evaluation with scores, using the protocol of
      orofacial myofunctional evaluation with scores (OMES). Their mandibular
      kinematics was assessed with a 3D motion capture system during deliberate
      unilateral gum chewing. The MSI was computed synthesizing the information
      contained in nine kinematics parameters into a single global figure. Patients'
      and controls' MSI were compared considering the preferred and non-preferred
      chewing side using a 2-way ANOVA (factors: group, side). RESULTS: Together with a
      lower total score of myofunctional orofacial status, the TMD group showed a
      reduced stability based on MSI (p<0.05). CONCLUSIONS: The MSI is an efficient
      method to measure the stability of the masticatory cycles. These preliminary
      results encourage validating the index on a larger sample. The variability in the
      motor behavior of chewing can impair the objectivity of its evaluations in
      several types of patients, including those with TMD. The MSI could be useful to
      complement clinical assessments, providing data for planning the rehabilitation
      of masticatory function in these patients.

PMID- 28759869
TI  - Shell-encoded Au nanoparticles with tunable electroactivity for specific dual
      disease biomarkers detection.
AB  - The exploration of electroactive labelling with tailorable and strong
      differential pulse voltammetry (DPV) responses is of great importance in accurate
      and sensitive screening of a panel of biomarkers related to cancer. Herein, shell
      encoded gold nanoparticles (Au NPs) are fabricated and give rise to shell species
      dominated DPV peak potentials. Two independent DPV peaks appear at -0.08V for
      Au@Cu2O core-shell NPs and 0.26V for Au@Ag core-shell NPs. Shell-encoded Au NPs
      drastically exhibit shell thickness-tunable amplified peak currents. The non
      interfering and amplified DPV responses enable shell-encoded Au NPs to be an
      alternative electrochemical signal amplifier for dual screening of
      carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). The limits of
      detection (LODs) are calculated to be 1.8pg/mL for CEA and 0.3pg/mL for AFP. In
      comparison to the parallel single-analyte assays, shell-encoded Au NPs engineered
      electrochemical aptasensors offer multiplexing capability and show significant
      prospects in biomedical research and early diagnosis of diseases.

PMID- 28759870
TI  - Highly efficient electrochemical sensing platform for sensitive detection DNA
      methylation, and methyltransferase activity based on Ag NPs decorated carbon
      nanocubes.
AB  - In this paper, we reported a sensitive and selective electrochemical method for
      quantify DNA methylation, analyzing DNA MTase activity and screening of MTase
      inhibitor based on silver nanoparticles (Ag NPs) decorated carbon nanocubes
      (CNCs) as signal tag. The Ag NPs/CNCs was prepared by in situ growth of
      nanosilver on carboxylated CNCs and used as a tracing tag to label antibody. The
      sensor was prepared by immobilizing the double DNA helix structure on the surface
      of gold electrode. When DNA MTase was introduced, the probe was methylated.
      Successively, anti-5-methylcytosine antibody labeled Ag NPs/CNCs was specifically
      conjugated on the CpG methylation site. The electrochemical stripping signal of
      the Ag NPs was used to monitor the activity of MTase. The electrochemical signal
      has a linear relationship with M.SssI activities ranging from 0.05 to 120U/mL
      with a detection limit of 0.03U/mL. In addition, we also demonstrated the method
      could be used for rapid evaluation and screening of the inhibitors of MTase. The
      newly designed strategy avoid the requirement of deoxygenation for
      electrochemical assay, and thus provide a promising potential in clinical
      application.

PMID- 28759872
TI  - Modeling the genetic complexity of Parkinson's disease by targeted genome edition
      in iPS cells.
AB  - Patient-specific iPSC are being intensively exploited as experimental disease
      models. Even for late-onset diseases of complex genetic influence, such as
      Parkinson's disease (PD), the use of iPSC-based models is beginning to provide
      important insights into the genetic bases of PD heritability. Here, we present an
      update on recently reported genetic risk factors associated with PD. We discuss
      how iPSC technology, combined with targeted edition of the coding or noncoding
      genome, can be used to address clinical observations such as incomplete
      penetrance, and variability in phenoconversion or age-at-onset in familial PD.
      Finally, we also discuss the relevance of advanced iPSC/CRISPR/Cas9 disease
      models to ascertain causality in genotype-to-phenotype correlation studies of
      sporadic PD.

PMID- 28759871
TI  - DNA origami nanorobot fiber optic genosensor to TMV.
AB  - In the quest of greater sensitivity and specificity of diagnostic systems, one
      continually searches for alternative DNA hybridization methods, enabling greater
      versatility and where possible field-enabled detection of target analytes. We
      present, herein, a hybrid molecular self-assembled scaffolded DNA origami entity,
      intimately immobilized via capture probes linked to aminopropyltriethoxysilane,
      onto a glass optical fiber end-face transducer, thus producing a novel biosensor.
      Immobilized DNA nanorobots with a switchable flap can then be actuated by a
      specific target DNA present in a sample, by exposing a hemin/G-quadruplex
      DNAzyme, which then catalyzes the generation of chemiluminescence, once the
      specific fiber probes are immersed in a luminol-based solution. Integrating
      organic nanorobots to inorganic fiber optics creates a hybrid system that we
      demonstrate as a proof-of-principle can be utilized in specific DNA sequence
      detection. This system has potential applications in a wide range of fields,
      including point-of-care diagnostics or cellular in vivo biosensing when using
      ultrathin fiber optic probes for research purposes.

PMID- 28759873
TI  - The alterations in alcohol dehydrogenase and aldehyde dehydrogenase activities in
      the sera of patients with renal cell carcinoma.
AB  - PURPOSE: In a previous study we showed that the total activity of alcohol
      dehydrogenase (ADH) and its isoenzyme class I was significantly higher in renal
      cancer (RCC) cells compared to normal kidney. The aim of this study was to
      compare the activities of ADH isoenzymes and aldehyde dehydrogenase (ALDH) in the
      sera of patients with different stages of RCC and healthy subjects. MATERIALS AND
      METHODS: Serum samples were taken from 54 patients with clear cell RCC (17
      patients in stage II, 22 in stage III and 15 in stage IV) and 52 healthy
      patients. Class III, IV of ADH and the total ADH activity was measured by the
      photometric method. For the measurement of ADH class I, II and the total ALDH
      activity we employed the fluorometric method. RESULTS: The total activity of ADH
      and its isoenzyme class I were significantly higher in the sera of patients with
      every stage of RCC compared to healthy subjects. The analysis of ALDH activity
      did not indicate significant differences between tested groups. CONCLUSIONS: The
      increased activity of total ADH and its isoenzyme class I in the sera of patients
      with RCC, seems to be caused by isoenzymes being released from cancerous cells
      and may be useful for diagnostics of renal cancer.

PMID- 28759874
TI  - Effects of vitamin E-diffused highly cross-linked UHMWPE particles on
      inflammation, apoptosis and immune response against S. aureus.
AB  - Particle-induced osteolysis and periprosthetic joint infection (PJI) are closely
      associated with periprosthetic tissue immune function. The objective of this
      study was to determine the effects of polyethylene particles on inflammation and
      response against S. aureus. Effects that vitamin E-diffused cross-linked UHMWPE
      (VE-PE) particles had on apoptosis, inflammation, and bactericidal activities
      compared to virgin cross-linked UHMWPE (control PE) particles were examined.
      Murine RAW 264.7 macrophages exposed to VE-PE particles in vitro were less
      apoptotic, secreted less tumor necrosis factor (TNF)-alpha, and responded more
      effectively against lipopolysaccharide or S. aureus compared to control PE
      particles. Implantation of VE-PE particles in murine calvaria in vivo caused less
      reactive oxygen species generation, less apoptosis, and less osteolysis compared
      to control PE particles. Implantation of PE particles in mice calvaria for 28
      days, followed by inoculation with S. aureus in the same site where PE particles
      were implanted, demonstrated enhanced S. aureus clearance in the VE-PE group at
      day 33 after inoculation. These findings indicate that VE-PE particles might be
      less inflammatory and might preserve innate immunity of local tissue, allowing
      for enhanced clearance of bacteria.

PMID- 28759875
TI  - An overview of benzo[b]thiophene-based medicinal chemistry.
AB  - Among sulfur containing heterocycles, benzothiophene and its derivatives are at
      the focus as these candidates have structural similarities with active compounds
      to develop new potent lead molecules in drug design. Benzo[b]thiophene scaffold
      is one of the privileged structures in drug discovery as this core exhibits
      various biological activities allowing them to act as anti-microbial, anti
      cancer, anti-inflammatory, anti-oxidant, anti-tubercular, anti-diabetic, anti
      convulsant agents and many more. Further, numerous benzothiophene-based compounds
      as clinical drugs have been extensively used to treat various types of diseases
      with high therapeutic potency, which has led to their extensive developments. Due
      to the wide range of biological activities of benzothiophene, their structure
      activity relationships (SAR) have generated interest among medicinal chemists,
      and this has culminated in the discovery of several lead molecules against
      numerous diseases. The present review is endeavoring to highlight the progress in
      the various pharmacological activities of benzo[b]thiophene derivatives. It is
      hoped that this review will be helpful for new thoughts in the quest for rational
      designs of more active and less toxic benzothiophene-based medicinal drugs, as
      well as more effective diagnostic agents and pathologic probes. Also, SAR studies
      that highlight the chemical groups responsible for evoking the potential
      activities of benzothiophene derivatives are studied and compared.

PMID- 28759876
TI  - Design, synthesis and antiproliferative activity of thiazolo[5,4-d]pyrimidine
      derivatives through the atom replacement strategy.
AB  - A series of thiazolo[5,4-d]pyrimidine derivatives were designed through the atom
      replacement strategy based on biologically validated scaffolds and then evaluated
      for their antiproliferative activities on cancer cell lines. The structure
      activity relationship studies were conducted, leading to the identification of
      compound 22, which exhibited good antiproliferative activity against HGC-27 with
      an IC50 value of 1.22 MUM and low toxicity against GES-1 cells. Mechanistic
      studies showed that compound 22 inhibited the colony formation and migration of
      HGC-27 as well as induced apoptosis. The western blot experiments proved that
      compound 22 up-regulated expression of Bax, down-regulated expression levels of
      Bcl-2 and cleaved caspased-3/9. These findings indicate that compound 22 may
      serve as a template for designing new agents for the treatment of human gastric
      cancers. The atom replacement strategy could be viable strategy for designing new
      anticancer drugs and may find its applications in drug design.

PMID- 28759877
TI  - Click chemistry-based synthesis and anticancer activity evaluation of novel C-14
      1,2,3-triazole dehydroabietic acid hybrids.
AB  - A concise and efficient synthetic approach has been established to readily access
      a series of novel C-14 1,2,3-triazole-tethered dehydroabietic acid derivatives in
      moderate to high yields. In vitro antiproliferative activity evaluation indicated
      that most of the hybrids exhibited potent inhibitory activities in a variety of
      cancer cell lines with low micromolar to submicromolar IC50 values. Further
      studies demonstrated that some of these analogues such as 20, 21, and 24 were
      also effective against adriamycin-resistant MCF-7 clone at low concentrations in
      a dose-dependent manner. Notably, the most potent compound 24, which possesses a
      3-(tert-butoxycarbonylamino)phenyl-substituted triazole moiety, not only
      exhibited obviously improved IC50 values ranging from 0.7 to 1.2 MUM against a
      panel of tested cancer cells, but also showed very weak cytotoxicity on normal
      cells. Preliminary mechanism studies indicated that compound 24 could induce
      apoptosis in MDA-MB-231 cells and was worth developing into a novel natural
      product-like anticancer lead by proper structure modification.

PMID- 28759878
TI  - Thienopyrimidine derivatives exert their anticancer efficacy via apoptosis
      induction, oxidative stress and mitotic catastrophe.
AB  - In this study, a series of 13 structural variants of thieno[2,3d]pyrimidine
      derivatives (6a-6m) were synthesized and screened for cytotoxicity in a panel of
      colorectal, ovarian, and brain cancer cell lines. The selectivity of the
      compounds was assessed by determining the cytotoxicity in normal epithelial cell
      line (CHO). The most potent compound, 6j, was efficacious (with IC50 range of 0.6
      1.2 MUM) in colon (HCT116 and HCT15), brain (LN-229 and GBM-10) and ovarian
      (A2780 and OV2008) cancer cell lines. In contrast, in the normal cell line (CHO),
      the IC50 values for 6j were 14 +/- 1.3 MUM. Compound 6j significantly inhibited
      the clonogenic potential of HCT116, OV2008 and A2780 cell lines in concentration 
      dependent (0.5-4 MUM) manner. Also, 6j induced 1) formation of reactive oxygen
      species; 2) apoptosis and 3) mitotic catastrophe in HCT116 and OV2008 cells (IC50
      = 0.5-2 MUM). Furthermore, apoptosis was the predominant mechanism of death in
      A2780 cells. The cytotoxicity of 6j in wild type HCT116 cells was similar to that
      in HCT116 cells lacking the apoptotic genes for Bax, Bak, or Bak and Bax,
      indicating that 6j induces mitotic catastrophe as alternative mechanism of death
      when when certain apoptotic proteins are absent. In summary, this study has
      identified a lead molecule, 6j, that selectively induces oxidative stress,
      apoptosis and mitotic catastrophe in specific cancer (colon and ovarian) cell
      lines.

PMID- 28759879
TI  - Structure-activity relations of rosmarinic acid derivatives for the amyloid beta
      aggregation inhibition and antioxidant properties.
AB  - Amyloid-beta aggregation inhibitors are expected to be therapeutic or
      prophylactic agents for Alzheimer's disease. Rosmarinic acid, which is one of the
      main aggregation inhibitors derived from Lamiaceae, was employed as a lead
      compound and its 25 derivatives were synthesized. In this study, the structure
      activity relations of rosmarinic acid derivatives for the amyloid-beta
      aggregation inhibitory effect (MSHTS assay), antioxidant properties, and xanthine
      oxidase inhibition were evaluated. Among the tested compounds, compounds 16d and
      19 were found to the most potent amyloid aggregation inhibitors. The SAR revealed
      that the necessity of the presence of the phenolic hydroxyl on one side of the
      molecule as well as the lipophilicity of the entire molecule. The importance of
      these structural properties was also supported by docking simulations.

PMID- 28759880
TI  - Automatic quantitative computed tomography segmentation and analysis of aerated
      lung volumes in acute respiratory distress syndrome-A comparative diagnostic
      study.
AB  - Quantitative lung computed tomographic (CT) analysis yields objective data
      regarding lung aeration but is currently not used in clinical routine primarily
      because of the labor-intensive process of manual CT segmentation. Automatic lung
      segmentation could help to shorten processing times significantly. In this study,
      we assessed bias and precision of lung CT analysis using automatic segmentation
      compared with manual segmentation. In this monocentric clinical study, 10
      mechanically ventilated patients with mild to moderate acute respiratory distress
      syndrome were included who had received lung CT scans at 5- and 45-mbar airway
      pressure during a prior study. Lung segmentations were performed both
      automatically using a computerized algorithm and manually. Automatic segmentation
      yielded similar lung volumes compared with manual segmentation with clinically
      minor differences both at 5 and 45 mbar. At 5 mbar, results were as follows:
      overdistended lung 49.58mL (manual, SD 77.37mL) and 50.41mL (automatic, SD
      77.3mL), P=.028; normally aerated lung 2142.17mL (manual, SD 1131.48mL) and
      2156.68mL (automatic, SD 1134.53mL), P = .1038; and poorly aerated lung 631.68mL
      (manual, SD 196.76mL) and 646.32mL (automatic, SD 169.63mL), P = .3794. At 45
      mbar, values were as follows: overdistended lung 612.85mL (manual, SD 449.55mL)
      and 615.49mL (automatic, SD 451.03mL), P=.078; normally aerated lung 3890.12mL
      (manual, SD 1134.14mL) and 3907.65mL (automatic, SD 1133.62mL), P = .027; and
      poorly aerated lung 413.35mL (manual, SD 57.66mL) and 469.58mL (automatic, SD
      70.14mL), P=.007. Bland-Altman analyses revealed the following mean biases and
      limits of agreement at 5 mbar for automatic vs manual segmentation: overdistended
      lung +0.848mL (+/-2.062mL), normally aerated +14.51mL (+/-49.71mL), and poorly
      aerated +14.64mL (+/-98.16mL). At 45 mbar, results were as follows: overdistended
      +2.639mL (+/-8.231mL), normally aerated 17.53mL (+/-41.41mL), and poorly aerated
      56.23mL (+/-100.67mL). Automatic single CT image and whole lung segmentation were
      faster than manual segmentation (0.17 vs 125.35seconds [P<.0001] and 10.46 vs
      7739.45seconds [P<.0001]). Automatic lung CT segmentation allows fast analysis of
      aerated lung regions. A reduction of processing times by more than 99% allows the
      use of quantitative CT at the bedside.

PMID- 28759882
TI  - Oculomotricity and Neurological Soft Signs: Can we refine the endophenotype? A
      study in subjects belonging to the spectrum of schizophrenia.
AB  - Alterations in eye tracking and motor impairments as well as Neurological Soft
      Signs (NSS) are frequently reported in patients with schizophrenia as well as in
      their relatives, and are proposed as endophenotype of the disease. This study
      investigated smooth pursuit eye movement and fixation task with distractors with
      a gap condition, two markers of inhibitory control mechanism, in 49 patients with
      schizophrenia, 24 ultra-high risk subjects, 41 full biological clinical siblings
      of patients and 48 controls. NSS were assessed as a marker of abnormal
      neurodevelopment. The results revealed more intrusive saccades respectively in
      smooth pursuit eye movement and in fixation task with distractors with a gap
      condition in patients, respect to controls and full siblings. Ultra high-risk
      participants with high NSS committed intrusive saccades compared to controls.
      Patients with schizophrenia with high NSS also displayed more of these
      abnormalities, compared to patients with schizophrenia with low NSS and controls.
      These findings highlight a global inhibitory control defect, and suggested that
      ultra-high risk subjects and patients with schizophrenia could share oculomotor
      abnormalities, especially when they express a high neurodevelopmental deviance.
      These oculomotor alterations might suggest that cerebral structures such as
      prefrontal and cerebellum could be involved in the expression of this
      vulnerability.

PMID- 28759883
TI  - Challenges to the census: international trends and a need to consider public
      health benefits.
AB  - The Canadian government decision to cancel the mandatory long-form census in 2010
      (subsequently restored in 2015), along with similar discussions in the United
      Kingdom (UK) and the United States of America (USA), have brought the purpose and
      use of census data into focus for epidemiologists and public health
      professionals. Policy decision-makers should be well-versed in the public health
      importance of accurate and reliable census data for emergency preparedness
      planning, controlling disease outbreaks, and for addressing health concerns among
      vulnerable populations including the elderly, low-income, racial/ethnic
      minorities, and special residential groups (e.g., nursing homes). Valid census
      information is critical to ensure that policy makers and public health
      practitioners have the evidence needed to: (1) establish incidence rates,
      mortality rates, and prevalence for the full characterization of emerging health
      issues; (2) address disparities in health care, prevention strategies and health
      outcomes among vulnerable populations; and (3) plan and effectively respond in
      times of disaster and emergency. At a time when budget and sample size cuts have
      been implemented in the UK, a voluntary census is being debated in the US. In
      Canada, elimination of the mandatory long-form census in 2011 resulted in
      unreliable population enumeration, as well as a substantial waste of money and
      resources for taxpayers, businesses and communities. The purpose of this article
      is to provide a brief overview of recent international trends and to review the
      foundational role of the census in public health management and planning using
      historical and current examples of environmental contamination, cancer clusters
      and emerging infections. Citing a general absence of public health applications
      of the census in cost-benefit analyses, we call on policy makers to consider its
      application to emergency preparedness, outbreak response, and chronic disease
      prevention efforts. At the same time, we call on public health professionals to
      improve published estimates of monetary benefit (via either cost-benefit or cost
      effectiveness analysis) to a given public health intervention.

PMID- 28759881
TI  - Prenatal particulate air pollution exposure and body composition in urban
      preschool children: Examining sensitive windows and sex-specific associations.
AB  - BACKGROUND: Evolving animal studies and limited epidemiological data show that
      prenatal air pollution exposure is associated with childhood obesity. Timing of
      exposure and child sex may play an important role in these associations. We
      applied an innovative method to examine sex-specific sensitive prenatal windows
      of exposure to PM2.5 on anthropometric measures in preschool-aged children.
      METHODS: Analyses included 239 children born >= 37 weeks gestation in an
      ethnically-mixed lower-income urban birth cohort. Prenatal daily PM2.5 exposure
      was estimated using a validated satellite-based spatio-temporal model. Body mass
      index z-score (BMI-z), fat mass, % body fat, subscapular and triceps skinfold
      thickness, waist and hip circumferences and waist-to-hip ratio (WHR) were
      assessed at age 4.0 +/- 0.7 years. Using Bayesian distributed lag interaction
      models (BDLIMs), we examined sex differences in sensitive windows of weekly
      averaged PM2.5 levels on these measures, adjusting for child age, maternal age,
      education, race/ethnicity, and pre-pregnancy BMI. RESULTS: Mothers were primarily
      Hispanic (55%) or Black (26%), had <= 12 years of education (66%) and never
      smoked (80%). Increased PM2.5 exposure 8-17 and 15-22 weeks gestation was
      significantly associated with increased BMI z-scores and fat mass in boys, but
      not in girls. Higher PM2.5 exposure 10-29 weeks gestation was significantly
      associated with increased WHR in girls, but not in boys. Prenatal PM2.5 was not
      significantly associated with other measures of body composition. Estimated
      cumulative effects across pregnancy, accounting for sensitive windows and within
      window effects, were 0.21 (95%CI = 0.01-0.37) for BMI-z and 0.36 (95%CI = 0.12
      0.68) for fat mass (kg) in boys, and 0.02 (95%CI = 0.01-0.03) for WHR in girls,
      all per ug/m3 increase in PM2.5. CONCLUSIONS: Increased prenatal PM2.5 exposure
      was more strongly associated with indices of increased whole body size in boys
      and with an indicator of body shape in girls. Methods to better characterize
      vulnerable windows may provide insight into underlying mechanisms contributing to
      sex-specific associations.

PMID- 28759884
TI  - Inter-relationships between physical activity, body mass index, sedentary time,
      and cognitive functioning in younger and older adults: cross-sectional analysis
      of the Canadian Community Health Survey.
AB  - OBJECTIVES: Engagement in leisure-time physical activity (LTPA) is protective
      against cognitive decline whereas obesity and sedentary behaviors are associated
      with impairments in perceived cognitive function. Currently, little is known
      about how these relationships vary across the lifespan. This study investigated
      the inter-relationships between LTPA, leisure-time sedentary time (LTST), body
      mass index (BMI), and perceived cognitive functioning in younger and older
      Canadian adults. STUDY DESIGN: This is a cross-sectional study. METHODS: Data
      from the 2012 annual component of the Canadian Community Health Survey (n =
      45,522; >=30 y) were used to capture LTPA, BMI, LTST, and perceived cognitive
      function. The inter-relationships were assessed using both mediation analyses and
      general linear models. RESULTS: Lower LTPA and higher BMI and LTST were related
      to poorer perceived cognitive functioning (P < 0.0001) and LTPA mediated the BMI
      perceived cognitive functioning (Sobel's test: t = 3.24; P < 0.002) and LTST
      perceived cognitive functioning (Sobel test: t = 3.35; P < 0.002) relationships.
      CONCLUSION: Higher LTPA levels contribute to better perceived cognitive
      functioning scores both independently and by way of offsetting the impact of
      elevated BMI and LTST on cognitive function.

PMID- 28759885
TI  - Identification of single nucleotide polymorphisms in carnosine-related genes and
      effects of genotypes on pork meat quality attributes.
AB  - Carnosine has pH-buffering and antioxidant properties that may bring advantages
      in terms of meat quality attributes. This study aimed at identifying
      polymorphisms in carnosine-related genes (CARNS1, SLC6A6, SLC15A3, SLC15A4) that
      might associate with muscle carnosine content and meat quality traits in pigs
      (Duroc, Landrace, Yorkshire). Twenty seven SNPs were identified and association
      analyses performed for SLC15A3 c.*35C>T and c.*52C>T (3' UTR region), and SLC15A4
      c.658A>G (Ile220Val) and c.818G>A (Ser273Asn) SNPs. Associations were observed
      for SNP c.658A>G with carnosine content, color b* and L*, drip and cooking
      losses, pH24h and glycolytic potential values (P<=0.05). The same associations
      were observed for SNP c.818G>A, but they were not significant after FDR
      correction. Results suggest that specific SLC15A4 gene variants might increase
      muscle carnosine content and improve meat quality. With a minor allele frequency
      of 0.17 for SNP c.658A>G in Yorkshire pigs, selection in favor of the c.658A
      allele may be considered as a mean to improve pork quality attributes.

PMID- 28759886
TI  - Divergent temperaments are associated with beef tenderness and the inhibitory
      activity of calpastatin.
AB  - Ninety-six feedlot-finished Nellore steers were used to verify the relationship
      between temperament indicators and meat tenderization. Temperament index (TI),
      chute score (CS), and average of exit velocity (EV) with CS (AT) presented low
      positive correlations (P<=0.05) with shear force, either at 2 or 16days
      postmortem (WBSF-16). The rectal temperature was consistently correlated with
      temperament indicators (TI, CS, and AT) and WBSF-16. Two groups (n=12)
      representing the most tender (39.2+/-4.9N) and most tough meat (94.1+/-11.8N),
      based on WBSF-16, were compared for temperament, and calpastatin activity (CASTa)
      was determined 48h postmortem. The tender group presented lower EV, TI, and AT
      (P<=0.05). The tender group exhibited lower (P<=0.05) CASTa in the triceps
      brachii muscle, but there was no difference in CASTa in the longissimus lumborum
      muscle between WBSF groups. Meat tenderness and inhibitory activity of
      calpastatin may be associated with divergent temperament indices in zebu cattle.

PMID- 28759887
TI  - The diagnostic accuracy of magnetic resonance angiography for blunt vertebral
      artery injury detection in trauma patients: A systematic review and meta
      analysis.
AB  - The role of magnetic resonance angiography (MRA) in the evaluation of patients
      with blunt vertebral artery has not been fully established. Our aim is to define
      the diagnostic accuracy of MRA in comparison to digital subtraction angiography
      (DSA) for the detection of blunt vertebral artery injury in trauma patients. A
      computer-assisted literature search of the PubMed, Scopus, Highwire, Web of
      Science, and LILACS was conducted, in order to identify studies reporting on the
      sensitivity and specificity of MRA in comparison to DSA for the detection of
      blunt vertebral artery injury in trauma patients. The Database search retrieved
      91 studies. Five studies fulfilled our eligibility criteria. Two authors assessed
      the risk of bias and applicability concerns using QUADAS-2. Two-by-two
      contingency tables were constructed on a per-vessel level. Heterogeneity was
      tested by the statistical significance of Cochran's Q, and was quantified by the
      Higgins's I2 metric. The pooled estimates of sensitivity and specificity for
      blunt vertebral artery injury detection with MRA in comparison to DSA were
      calculated based on the bivariate model. The meta-analysis was supplemented by
      subgroup and sensitivity analysis, as well as analysis for publication bias.
      There was significant clinical heterogeneity in the targeted population,
      inclusion criteria, and MRA related parameters. The reporting bias and
      applicability concerns were moderate and low, respectively. In the overall
      analysis, the sensitivity ranged from 25% to 85%, while the specificity varied
      from 65% to 99%, across studies. According to the bivariate model, the pooled
      sensitivity and specificity of MRA in the evaluation of patients with blunt
      vertebral artery was as high as 55% (95% CI 32.1%-76.7%), and 91% (95% CI 66.3%
      98.2%), respectively. Subgroup analysis in terms of MRA sequence sensitivity of
      phase, the contrasted MRA (75% [95% CI 43%-92%]) seemed to be superior to the TOF
      MRA (46% [95%CI 20%-74%]). The addition of contrast enhancement did not seem to
      improve the diagnostic yield of MRA. The Egger's test did not identify any
      significant publication bias (p=0.2). An important limitation of the current meta
      analysis is the small number of eligible studies, as well as the lack of studies
      on newer, high-field MR scanners. We concluded that MRA has a moderate diagnostic
      accuracy in the diagnosis of blunt vertebral artery injuries. Further studies on
      high-field magnetic resonance scanners are recommended.

PMID- 28759888
TI  - High-temperature crystallization of nanocrystals into three-dimensional
      superlattices.
AB  - Crystallization of colloidal nanocrystals into superlattices represents a
      practical bottom-up process with which to create ordered metamaterials with
      emergent functionalities. With precise control over the size, shape and
      composition of individual nanocrystals, various single- and multi-component
      nanocrystal superlattices have been produced, the lattice structures and chemical
      compositions of which can be accurately engineered. Nanocrystal superlattices are
      typically prepared by carefully controlling the assembly process through solvent
      evaporation or destabilization or through DNA-guided crystallization. Slow
      solvent evaporation or cooling of nanocrystal solutions (over hours or days) is
      the key element for successful crystallization processes. Here we report the
      rapid growth (seconds) of micrometre-sized, face-centred-cubic, three-dimensional
      nanocrystal superlattices during colloidal synthesis at high temperatures (more
      than 230 degrees Celsius). Using in situ small-angle X-ray scattering, we observe
      continuous growth of individual nanocrystals within the lattices, which results
      in simultaneous lattice expansion and fine nanocrystal size control due to the
      superlattice templates. Thermodynamic models demonstrate that balanced attractive
      and repulsive interparticle interactions dictated by the ligand coverage on
      nanocrystal surfaces and nanocrystal core size are responsible for the
      crystallization process. The interparticle interactions can also be controlled to
      form different superlattice structures, such as hexagonal close-packed lattices.
      The rational assembly of various nanocrystal systems into novel materials is thus
      facilitated for both fundamental research and for practical applications in the
      fields of magnetics, electronics and catalysis.

PMID- 28759891
TI  - Doctors falling down on the job.

PMID- 28759890
TI  - Maturity status influences the relative age effect in national top level youth
      alpine ski racing and soccer.
AB  - Since the relative age effect (RAE) characterizes a problem in all age categories
      of alpine ski racing and soccer and the fact that, yet, to date the underlying
      factors have not been well investigated, the aim of the present study was to
      assess the influence of the biological maturity status on the RAE among youth
      alpine ski racers (YSR) and soccer players (SP). In total, 183 male and female
      YSR selected for national final races and 423 male SP selected for Elite Youth
      Development Centres were investigated. Additionally, a comparison group of 413
      non-athletes was evaluated. The birth months were split into four relative age
      quarters. The biological maturity status was assessed by the age at peak height
      velocity (APHV) method; according to the M+/-SD of the comparison group, the
      athletes were divided into normal, early and late maturing. Chi2-tests indicated
      a significant RAE among YSR (chi2(3,N = 183) = 18.0; p<0.001; omega = 0.31) and
      SP (chi2(3,N = 423) = 33.1; p<0.001; omega = 0.28). In total, only a small number
      of late maturing athletes were present (0.5-2.3%). Among relatively younger
      athletes, high percentages of early maturing athletes were found (43.1-43.3%).
      The findings indicate that relatively younger and less mature athletes are
      marginalized or totally excluded in alpine ski racing and soccer. Thus, selection
      criteria in both sports are effectively based on early biological development and
      relatively older age, both of which should be considered in future in the talent
      selection process. In this context, the easy feasible method of assessing the
      APHV can be used.

PMID- 28759889
TI  - Mitotic progression following DNA damage enables pattern recognition within
      micronuclei.
AB  - Inflammatory gene expression following genotoxic cancer therapy is well
      documented, yet the events underlying its induction remain poorly understood.
      Inflammatory cytokines modify the tumour microenvironment by recruiting immune
      cells and are critical for both local and systemic (abscopal) tumour responses to
      radiotherapy. A poorly understood feature of these responses is the delayed onset
      (days), in contrast to the acute DNA-damage responses that occur in minutes to
      hours. Such dichotomous kinetics implicate additional rate-limiting steps that
      are essential for DNA-damage-induced inflammation. Here we show that cell cycle
      progression through mitosis following double-stranded DNA breaks leads to the
      formation of micronuclei, which precede activation of inflammatory signalling and
      are a repository for the pattern-recognition receptor cyclic GMP-AMP synthase
      (cGAS). Inhibiting progression through mitosis or loss of pattern recognition by
      stimulator of interferon genes (STING)-cGAS impaired interferon signalling.
      Moreover, STING loss prevented the regression of abscopal tumours in the context
      of ionizing radiation and immune checkpoint blockade in vivo. These findings
      implicate temporal modulation of the cell cycle as an important consideration in
      the context of therapeutic strategies that combine genotoxic agents with immune
      checkpoint blockade.

PMID- 28759893
TI  - Kilmartin's castigation of physicians, medical society regarding warrantless
      searches into PDMP demeans AG's office.

PMID- 28759892
TI  - The Core of Medical Ethics.

PMID- 28759894
TI  - "3 Good Things" in Recovery.

PMID- 28759895
TI  - Assessing acceptability and feasibility of provider-initiated HIV testing and
      counseling in Ghana.
AB  - t In Ghana, HIV voluntary counseling and testing remains poorly utilized. The
      World Health Organization (WHO) has recommended opt-out, provider-initiated
      testing and counseling (PITC) in order to increase utilization and earlier
      intervention. Yet implementation challenges remain in resource-scarce settings.
      This study sought to better understand the dynamics of providing PITC at Apam
      Catholic Hospital, a district referral hospital in Ghana. Semi-structured
      interviews were conducted with healthcare providers and patients exploring
      attitudes regarding PITC, community stigma, and HIV knowledge. Results showed
      healthcare providers believed PITC would lead to earlier diagnosis and
      intervention, but concerns persisted over increased costs. Patients welcomed
      PITC, but expressed discomfort in opting-out. Patients demonstrated incomplete
      HIV knowledge and widely believed spiritual healers and prayer can cure the
      infection. Acceptance of PITC by both healthcare providers and patients remains
      high, but concerns over resource costs and HIV knowledge persist as challenges.
      [Full article available at http://rimed.org/rimedicaljournal-2017-08.asp].

PMID- 28759897
TI  - Pulmonary Hypertension in a Patient with Hereditary Hemorrhagic Telangiectasia.
AB  - t Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu
      Disease, is an autosomal dominant genetic disorder that is characterized by the
      abnormal development of blood vessels. While the pathophysiology underlying the
      development of pulmonary hypertension (PH) in patients with HHT is not fully
      understood, it is believed to occur by one of two mechanisms: increases in
      pulmonary vascular resistance or cardiac output. In the following report, we
      describe an interesting case of a 26-year-old woman with HHT whose right heart
      catheterization initially demonstrated PH with elements of both pre- and post
      capillary PH. Once the pre-capillary PH component was treated, however, an
      underlying high-normal cardiac-output state was unmasked. [Full article available
      at http://rimed.org/rimedicaljournal-2017-08.asp].

PMID- 28759896
TI  - An analysis of diagnoses that drive readmission: What can we learn from the
      hospitals in Southern New England with the highest and lowest readmission
      performance?
AB  - : Background: The Hospital Readmission Reduction Program was instituted by the
      Centers for Medicare & Medicaid Services in 2012 to incentivize hospitals to
      reduce readmissions. OBJECTIVE: To examine the most common diagnoses driving
      readmissions among fee-for-service Medicare beneficiaries in the hospitals with
      the highest and lowest readmission performance in Southern New England from 2014
      to 2016. METHODS: This is a retrospective observational study using publicly
      available Hospital Compare data and Medicare Part A claims data. Hospitals were
      ranked based on risk-adjusted excess readmission ratios. Patient demographic and
      hospital characteristics were compared for the two cohorts using t-tests. The
      percentages of readmissions in each cohort attributable to the top three
      readmission diagnoses were examined. RESULTS: Highest-performing hospitals
      readmitted a significantly lower percentage of black patients (p=0.03), were less
      urban (p<0.01), and had higher Hospital Compare Star ratings (p=0.01). Lowest
      performing hospitals readmitted higher percentages of patients for sepsis (9.4%
      [95%CI: 8.8%-10.0%] vs. 8.1% [95%CI: 7.4%-8.7%]) and complications of device,
      implant, or graft (3.2% [95%CI: 2.5%-3.9%] vs. 0.2% [95%CI: 0.1%-0.6%]), compared
      to highest-performing hospitals. CONCLUSIONS: Ongoing efforts to improve care
      transitions may be strengthened by targeting early infection surveillance,
      promoting adherence to surgical treatment guidelines, and improving communication
      between hospitals and post-acute care facilities. [Full article available at
      http://rimed.org/rimedicaljournal-2017-08.asp].

PMID- 28759898
TI  - Unusual Mechanism for Superior Mesenteric Artery Syndrome after Scoliosis
      Surgery.
AB  - t Superior Mesenteric Artery (SMA) syndrome is an uncommon condition caused by
      mechanical obstruction of the distal third of the duodenum between the superior
      mesenteric artery and the abdominal aorta. SMA syndrome is associated with both
      operative and non-operative corrections of scoliosis, as well as anorexia
      nervosa, severe weight loss, tumors, burns, and other traumas.[1-4] We report an
      unusual case of SMA syndrome following corrective surgery for scoliosis in which
      post-operative gastric distension caused duodenal compression that subsequently
      resolved with gastric decompression, as opposed to the conventional, reverse
      series of events in which SMA syndrome causes the gastric dilatation. [Full
      article available at http://rimed.org/rimedicaljournal-2017-08.asp].

PMID- 28759899
TI  - A soccer mom with chest pain: Spontaneous coronary artery dissection in a young
      woman.

PMID- 28759900
TI  - Advantages of Cardiac Magnetic Resonance Imaging for Severe Pectus Excavatum
      Assessment in Children.
AB  - AIM:  Cardiac function can be impaired in patients with pectus excavatum (PE) due
      to anatomic and dynamic compression of the heart. Efforts for radiation dose
      reduction in imaging techniques have allowed cardiac magnetic resonance imaging
      (c-MRI) to play a major role in PE assessment. The aim of our study is to
      describe the findings of c-MRI 18 months after we changed the PE assessment
      protocol from chest computed tomography to c-MRI. PATIENTS AND METHODS:  Since
      mid-2015 all patients with severe PE (suspected Haller's index > 3.2) were
      assessed with inspiratory and expiratory c-MRI. A retrospective analysis of these
      patients was performed evaluating the following parameters: (1) Radiologic PE
      indexes (Haller's, correction and asymmetry indexes; and sternal rotation) and
      (2) cardiac function (including left and right ventricle ejection fraction).
      RESULTS:  A total of 20 patients met the inclusion criteria. Dynamic imaging
      showed a significant difference during inspiration and expiration of the Haller's
      index 3.85 (range: 3.17-7.3) versus 5.10 (range: 3.85-10.8) (p < 0.05), and
      correction index (26.86% vs. 36.84%, respectively, p < 0.05). The sternal
      rotation was 14.5 (range: 0-36). c-MRI analysis disclosed a right ventricle
      ejection fraction of 50.3%. (normal range: 61% [54-71%]). Echocardiographic
      imaging underestimated the functional repercussion of PE in all patients.
      CONCLUSION:  Initial results show that PE assessment by c-MRI allows a radiation
      free image of the chest wall deformity during the entire breathing process. Also,
      it permitted the evaluation of the influence of sternum impingement on cardiac
      function. These findings allowed us a careful surgical evaluation and
      preoperative planning.

PMID- 28759901
TI  - Subsequent Injuries and Early Recurrent Diagnoses in elite Rugby Union Players.
AB  - An eight-season (2005/06-2012/13) prospective cohort design was used to record
      time-loss injuries in 15 English Premiership teams. Data pertaining to a total of
      1 556 players and 9 597 injuries (8 180 subsequent) were included in the
      analysis. Injuries subsequent to an index injury were classified as (1) New:
      different site; (2) Local: same site (and different type); or (3) Recurrent: same
      site and type. The severity of subsequent injuries (days missed) was compared
      with their related index injury. The proportions of early (<2 months), late (2-12
      months) and delayed (>12 months) subsequent injuries were compared across injury
      classifications and diagnosis groupings. The majority of subsequent injuries
      (70%) were classified as new injuries, with 14% local and 16% recurrent. A large
      proportion of recurrent subsequent injuries (42%) occurred within two months of
      return-to-play. Subsequent injuries were not more severe than their corresponding
      index injury (effect sizes <0.20). Specific local and recurrent subsequent injury
      diagnoses with the highest risk of occurring within two months of return-to-play
      were: 'neck muscle strain', 'ankle joint capsule sprain', and 'cervical nerve
      root' injuries. These findings may be used to drive targeted secondary prevention
      efforts, such as reconsideration of return-to-play protocols for neck muscle
      strain injuries.

PMID- 28759902
TI  - [Complications of DMEKeratoplasty: Avoid, Recognize and Treat].
AB  - Descemet membrane endothelial keratoplasty (DMEK) has evolved into a routine
      surgical procedure for posterior lamellar keratoplasty. After its introduction
      more than 10 years ago, several modifications in grafting technique and
      postoperative treatment regimen helped to improve its safety and reproducibility.
      Although DMEK offers faster and better improvements in visual acuity, as well as
      less graft rejections when compared to Descemet's stripping (automated)
      endothelial keratoplasty (DS[A]EK), difficulties when implementing this technique
      hamper the widespread use in many areas. However, different strategies help to
      reduce the rate of intra- and postoperative complications, making DMEK the method
      of choice for most patients with corneal endothelial diseases. Certain techniques
      help to reduce the endothelial damage during graft preparation; correct matching
      of donor age and recipient's anterior chamber depth eases intracameral unfolding
      of the DMEK graft, the use of SF6 gas for anterior chamber tamponade reduces the
      need for additional rebubblings, and the correct frequency and duration of
      postoperative topical steroid treatment helps to reduce the development of
      cystoid macular edema and graft rejections. Further standardization, but also
      individualization, of DMEK helps to offer this treatment option to patients with
      more complex anterior segment situations like anterior synechia, larger iris
      defects and glaucoma drainage devices.

PMID- 28759903
TI  - [Telephone Aftercare by Social Services to Improve Return to Work after Medical
      Rehabilitation].
AB  - Aim Many patients are discharged from the rehabilitation clinic with a restored
      working ability, but are often unemployed or there is a mismatch between their
      skills and the job requirements. Those patients often feel to be left alone with
      their problems regarding their adequate occupational reintegration and wish to be
      supported over the course of stationary rehabilitation in terms of socio-legal
      and social-medical issues. The randomized controlled trial investigated if a 12
      month telephone aftercare conducted by staff of the social service has a positive
      influence on occupational reintegration. Method Patients with severe limitations
      of work-related functioning were recruited in one rehabilitation center and
      randomized at the end of rehabilitation. The intervention group (N=171) received
      a telephone aftercare for 12 month by staff of the social service, the control
      group (N=162) received the standard aftercare recommendation. The risk of an
      unsuccessful occupational reintegration was operationalized by means of 3 items,
      which where summed up to a risk index. The evaluation of the aftercare was
      conducted by written survey on 3 measurement points. Results Overall 333 patients
      were included in the study. 45% (N=152) of the sample were female, the mean age
      was 50 years. 12 month after rehabilitation 71% (N=120) of patients from the
      intervention group stated to be employed. In the control group the proportion
      amounts to 68% (N=110; p=0.074, CI -0.0718; 0.1252). The control group has a
      significant higher risk constellation according to the risk score for
      occupational reintegration as the intervention group. Conclusion The risk score
      shows significant advantages for patients in the intervention group. The risk of
      a non-successful reintegration 12 month after rehabilitation was significant
      lower in the intervention group. All further occupational and health related
      outcomes indicate only moderate differences. These should be considered against
      the background of the low-threshold intervention. The telephone aftercare by
      staff of the social service was rated as very helpful by most of the patients in
      the intervention group.

PMID- 28759905
TI  - Stroke Prevention.

PMID- 28759904
TI  - Amytis Towfighi, MD.

PMID- 28759906
TI  - Modifiable Risk Factors for Stroke and Strategies for Stroke Prevention.

PMID- 28759907
TI  - Nutrition in Stroke Prevention.

PMID- 28759908
TI  - The Role of Diabetes, Obesity, and Metabolic Syndrome in Stroke.

PMID- 28759909
TI  - Blood Pressure and Prevention of Stroke.

PMID- 28759910
TI  - Treating Dyslipidemia for the Primary and Secondary Prevention of Stroke.

PMID- 28759911
TI  - Systematic Review and Meta-Analysis of Psychosocial Risk Factors for Stroke.

PMID- 28759912
TI  - Large Artery Atherosclerosis: Extracranial and Intracranial.

PMID- 28759913
TI  - Prevention of Cerebral Small Vessel Disease.

PMID- 28759914
TI  - Cardioembolic Stroke: Mechanisms and Therapeutics.

PMID- 28759915
TI  - Cerebral Arteriopathies, Venous Thrombosis, and Migraine.

PMID- 28759916
TI  - Single Gene Causes of Stroke.

PMID- 28759917
TI  - Antiplatelet Therapy in Noncardioembolic Stroke: A Review of Current Evidence.

PMID- 28759918
TI  - Special Considerations for Primary and Secondary Stroke Prevention in Women.

PMID- 28759919
TI  - Organized Outpatient Care of Patients with Transient Ischemic Attack and Minor
      Stroke.

PMID- 28759920
TI  - [A Decade of Online Physician-Rating Websites in Germany: an Assessment of the
      Current Level of Development].
AB  - OBJECTIVE: On physician-rating websites (PRW), patients have the opportunity to
      search for physicians and also evaluate their performance. PRW in Germany has
      been in existence for a decade; this study aims to provide an overview of the
      current level of their significance for both patients and the health care system.
      METHODS: (1) A systematic internet search was carried out to identify German PRW.
      (2) Online-derived cross-sectional data (N=1,044 respondents) were analyzed with
      respect to awareness, usage, and impact of PRW as well as patient preferences
      when searching online for physicians. (3) An analysis of the structure of online
      ratings for a random sample of 11% of German dermatologists was conducted.
      RESULTS: In total, we identified 29 PRWs. Slightly more than half of all
      respondents (54%) were aware of German PRW and every fourth respondent has
      already used PRW to search for a physician. Approximately 70% of all users stated
      they had already made a decision for or against a particular physician based on
      the quality ratings shown on PRW. Almost all dermatologists could be identified
      on PRW and 93% have already been rated on any PRW (mean number of ratings:
      24.55). More than half of all ratings (55%) were positive. CONCLUSION: After one
      decade of development, PRWs seem to have gained significant importance in the
      German health care sector. However, high-quality and adequately powered
      randomized controlled trials are required to determine the impact of PRWs on
      patient steerage.

PMID- 28759921
TI  - Over-the-scope clip is an effective therapy for postbanding ulcer bleeding after
      initially successful transjugular intrahepatic portosystemic shunt therapy.

PMID- 28759922
TI  - Peroral endoscopic myotomy (POEM) in jackhammer esophagus: a trick of the trade.

PMID- 28759923
TI  - A novel mechanical simulator for hands-on bariatric endoscopy training in
      intragastric balloon placement.

PMID- 28759924
TI  - A novel technique for biliary polypectomy.

PMID- 28759925
TI  - Hilar cholangiocarcinoma diagnosed by endoscopic ultrasound-guided
      hepaticogastrostomy and cholangioscopy.

PMID- 28759926
TI  - Uneven double-lumen cannula for rescue guidewire technique in endoscopic
      ultrasonography-guided hepaticogastrostomy.

PMID- 28759927
TI  - Endoscopic treatment of Zenker's diverticulum using a stag beetle knife.

PMID- 28759928
TI  - Safe technique for direct percutaneous endoscopic jejunostomy tube placement
      using single-balloon enteroscopy with fluoroscopy.

PMID- 28759929
TI  - Gastric peroral endoscopic myotomy for gastroparesis, after botulinum toxin
      injection.

PMID- 28759930
TI  - Extraction of an ingested denture embedded in the jejunum by mucosal cutting.

PMID- 28759931
TI  - Endoscopic ultrasound-guided gastrojejunostomy: a novel technique.

PMID- 28759932
TI  - Water pressure method for duodenal endoscopic submucosal dissection.

PMID- 28759933
TI  - Hypotension and Brain Injury in Asphyxiated Newborns Treated with Hypothermia.
AB  - OBJECTIVE: This study aimed to assess the incidence of hypotension in asphyxiated
      newborns treated with hypothermia, the variability in treatments for hypotension,
      and the impact of hypotension on the pattern of brain injury. STUDY DESIGN: We
      conducted a retrospective cohort study of asphyxiated newborns treated with
      hypothermia. Mean blood pressures, lactate levels, and inotropic support
      medications were recorded during the hospitalization. Presence and severity of
      brain injury were scored using the brain magnetic resonance imaging (MRI)
      obtained after the hypothermia treatment was completed. RESULTS: One hundred and
      ninety term asphyxiated newborns were treated with hypothermia. Eighty-one
      percent developed hypotension. Fifty-five percent of the newborns in the
      hypotensive group developed brain injury compared with 35% of the newborns in the
      normotensive group (p = 0.04). Twenty-nine percent of the newborns in the
      hypotensive group developed severe brain injury, compared with only 15% in the
      normotensive group. Nineteen percent of the newborns presenting with volume-
      and/or catecholamine-resistant hypotension had near-total injury, compared with
      6% in the normotensive group and 8% in the group responding to volume and/or
      catecholamines. CONCLUSION: Hypotension was common in asphyxiated newborns
      treated with hypothermia and was associated with an increased risk of (severe)
      brain injury in these newborns.

PMID- 28759934
TI  - [Apnea Detection by Means of Respiratory Sound Recordings and Polysomnography - A
      Comparative Study].
AB  - Introduction In this study, recognition of apnoeas by means of polysomnography
      (PSG) and nocturnal respiratory sound recordings in patients with obstructive
      sleep apnoea (OSA) was analyzed and compared. Methods In 45 patients with OSA
      requiring treatment (AHI > 15/h), concomitant polysomnographic recordings and
      long term respiratory sound recordings by means of LEOSound were performed.
      Patients' average age was 58 +/- 12 years (mean +/- standard deviation), average
      BMI was 33 +/- 7 kg/m2. Audio-visual apnoea detection by LEOSound was compared to
      polysomnographic apnoea detection. Increased artifact rate due to dislocation of
      microphones led to rejection of 11 out of 45 recordings for detailed analysis.
      Results Comparison of apnea detection by audio-visual analysis and
      polysomnography yielded a median of 164 apneas for LEOSound recordings and 158
      apneas for PSG. Median apnoea index (AI) was calculated to be 20/h for
      respiratory sounds recording and 21/h for PSG. The correlation of apnea indices
      from acoustic long term registration and PSG was 0.939 (p < 0.001). Discussion
      Acoustic long term registration of primary and secondary respiratory sounds is
      also capable to recognize apnoeas. Exact differentiation between apnoeas and
      hypopnoeas is only possible in a limited fashion.

PMID- 28759935
TI  - A Rapid and Sensitive UPLC-MS/MS Method for Quantification of Bruceantinol in Rat
      Plasma and Its Application to a Pharmacokinetic Study.
AB  - Bruceantinol (BOL), a quassinoid compound isolated from the fruits of Brucea
      javanica, has been reported to have cytotoxic and antibacterial effects. In this
      study, a rapid, sensitive, and specific ultra-performance liquid chromatography
      with tandem mass spectrometry (UPLC-MS/MS) method was developed for the
      quantitative determination of BOL in rat plasma. The samples were treated by
      simple liquid-liquid extraction with ethyl acetate and separated on an UPLC BEH
      C18 column (2.1 mm * 50 mm) using a 3-min gradient elution scheme, which consists
      of water (0.1% v/v, formic acid) and methanol (0.1%, v/v, formic acid) to achieve
      the separation of BOL and sinomenine (IS) with high selectivity. The electrospray
      ionization source was used in positive ion mode; the multiple reaction monitoring
      quantified the target fragment ions m/z 629.6 -> 569.5 for BOL and m/z 330.5 ->
      207.3 for IS. This work was evaluated with regards to the specificity, extraction
      recovery, matrix effect, linearity, accuracy, precision, stability, and dilution
      integrity. This approach was used to examine the pharmacokinetics of BOL in rats
      after oral (0.3 mg/kg) and intravenous (0.15 mg/kg) administration. BOL presented
      fast excretion and very low oral bioavailability.

PMID- 28759936
TI  - The Impact of the Cosurgeon Model on Bilateral Autologous Breast Reconstruction.

PMID- 28759937
TI  - Prevalence, Clinical Features, and Natural History of Incidental Clinically Non
      Functioning Pituitary Adenomas.
AB  - The objective of the study was to assess the prevalence and clinical features of
      incidentally discovered clinically non-functioning pituitary adenoma (CNFPA) and
      to analyze its natural history. A multicenter retrospective study in patients
      diagnosed with incidental CNFPA periodically followed-up in 3 specialized
      neuroendocrinology units from 1992 to 2015 was performed. Out of a total of 189
      CNFPA patients, 57 cases (30.1%; 29 women; age at diagnosis 55.8+/-16.7 years)
      were incidental. Most patients (n=55, 96.5%) were diagnosed by magnetic resonance
      imaging (MRI). A sum of 71.9% (n=41) were macroadenomas; 2 of them (3.5%) were
      giant adenomas (>=4 cm). Patients with macroadenomas were older than those with
      microadenomas (59.5+/-16.7 vs. 46.4+/-18.1 years, p=0.007). Macroadenomas were
      more common in men (85.7% vs. 58.6%, p=0.023). Twenty-eight patients (49.1%)
      showed suprasellar extension; of these, 19 were accompanied by chiasmatic
      compression. Hypopituitarism was present in 14 (24.6%) patients; which was
      partial in 13 patients (22.8%) and complete in one patient (1.8%). The gonadal
      axis was the most frequently affected (n=13, 22.8%). Twenty four patients (42.1%)
      underwent surgery. Of the non-operated patients, 26 patients could be evaluated
      morphologically after a median follow-up of 15.5 months (interquartile range, 5.7
      32.7 months). No significant changes were found in the maximum tumor diameter at
      the end of follow-up (1.2+/-0.6 vs 1.2+/-0.7 cm). The majority of CNFPAs
      evaluated (n=23, 88.5%) did not show any changes in size. In 2 cases (7.7%) tumor
      size decreased, and in one patient (3.8%) increased. In our series of CNFPA
      patients, approximately one-third were incidental. These tumors were diagnosed by
      MRI preferably from the 5th decade of life without sex predilection. Most of them
      were macroadenomas, more commonly diagnosed in men and at an older age, compared
      to microadenomas. The suprasellar extension with chiasmatic compression and
      hypopituitarism were frequent at diagnosis. Most of the non-operated incidental
      CNFPAs remain with stable tumor size over time, growth being an unusual event.

PMID- 28759938
TI  - Irisin and Testosterone in Men with Metabolic Syndrome.
AB  - The beneficial effects of testosterone on the metabolism and body composition of
      men are well established but the exact mechanisms of these effects are not
      clearly understood. A potential explanation might lie in the hormones, secreted
      from skeletal muscles, named "myokines". One such myokine, irisin, has been shown
      to also have potential beneficial metabolic effects. The aim of this pilot study
      was to evaluate the association of serum testosterone with circulating serum
      irisin levels in men with metabolic syndrome. A total 128 men with metabolic
      syndrome (MS) based on the IDF criteria participated in the study. Irisin serum
      concentration was determined by means of ELISA. Mean age+/-SD of the study
      participants was 51.8+/-8.3 years. Seventy percent of the subjects had type 2
      diabetes mellitus. Circulating irisin was inversely associated with serum
      testosterone (r=-0.279, p<0.01) and was significantly higher in subjects with
      hypogonadism - mean+/-SD 252.0+/-147.1 vs.172.9+/-92.2 ng/ml (p=0.002). ROC
      analysis of serum irisin value was determined for distinguishing subjects with
      hypogonadism (AUC=0.670). In a multiple linear regression model with BMI, FPG,
      age, and irisin, only BMI (beta=-0.228, p=0.004) and irisin (beta=-0.170,
      p=0.045) were variables independently associated with testosterone
      concentrations. Irisin is negatively associated with serum testosterone in our
      population sample of men with MS. This might suggest a possible involvement of
      myokines and testosterone with regards to the human metabolism. As no such data
      on this association has been reported in the literature thus far, further
      prospective studies are required to elucidate this correlation.

PMID- 28759939
TI  - Effects of a Low-Calorie, Low-Carbohydrate Soy Containing Diet on Systemic
      Inflammation Among Patients with Nonalcoholic Fatty Liver Disease: A Parallel
      Randomized Clinical Trial.
AB  - Few studies have focused on the effects of a soy containing diet on inflammation
      and serum leptin level among patients with nonalcoholic fatty liver disease
      (NAFLD). Therefore, we aimed to determine the effects of such a diet in patients
      with NAFLD. Forty-five patients with NAFLD participated in this parallel
      randomized clinical trial for 8 weeks. Patients were randomly allocated to these
      3 groups: 1) a low-calorie diet, 2) low-calorie low-carbohydrate diet, and 3) low
      calorie low-carbohydrate soy containing diet. Low-calorie low-carbohydrate soy
      containing diet reduced fasting blood sugar (FBS) and serum insulin level
      significantly compared to other 2 groups (-11.6+/-2.8 vs. -6.3+/-1.7 and -3.1+/
      1.0 mg/dl for FBS; and -5.1+/-1.2  vs. -1.2+/-0.3 and -1.7+/-0.5 mg/dl for serum
      insulin level). Serum hs-CRP level was also reduced significantly following low
      calorie low-carbohydrate soy containing diet (-0.8+/-0.1 vs. -0.1+/-0.06 and 
      0.1+/-0.06 mg/dl). Both systolic and diastolic blood pressures were reduced
      significantly. Changes in leptin level tended to be different among 3 groups.
      After trial, 5 patients in each intervention group did not have NAFLD. From 6
      patients in grade 2 at the beginning only 1 patient remained and others moved to
      grade 1. Low-calorie low-carbohydrate soy containing diet could reduce glycemic
      indices, hs CRP, systolic and diastolic blood pressure in a significant level in
      patients with NAFLD. However, these effects were dependent on baseline weight and
      further studies are needed to clarify the effect of such interventions in
      subjects with different BMI categories.

PMID- 28759940
TI  - Impact of Aldosterone Synthase Inhibitor FAD286 on Steroid Hormone Profile in
      Human Adrenocortical Cells.
AB  - Inhibition of aldosterone synthase (CYP11B2) is an alternative treatment option
      to mineralocorticoid receptor antagonism to prevent harmful aldosterone effects.
      FAD286 is the best characterized aldosterone synthase inhibitor. However, to
      date, no study has used sensitive liquid chromatography-tandem mass spectrometry
      to characterize in detail the effect of FAD286 on the secreted steroid hormone
      profile of adrenocortical cells. Basal aldosterone production in NCI-H295R cells
      was detectable and 9-fold elevated after stimulation with angiotensin II. FAD286
      inhibited this increase, showing a maximal effect at 10 nmol/l. Higher
      concentrations of FAD286 did not further reduce aldosterone concentrations, but
      showed a parallel reduction in corticosterone, cortisol and cortisone levels,
      reflecting additional inhibition of steroid-11beta-hydroxylase (CYP11B1).
      Pregnenolone, progesterone and 17-OH-progesterone levels remained unaffected. In
      conclusion, the aldosterone synthase inhibitor FAD286 lowers angiotensin II
      induced aldosterone concentrations in adrenocortical cells but the relative lack
      of selectivity over CYP11B1 is evident at higher FAD286 concentrations.

PMID- 28759941
TI  - Maternal High-Fat Diet During Pregnancy and Lactation has Opposite Effects on
      Gonadal Expression of Leptin and Leptin Receptor in Rat Dams and Their Offspring.
AB  - This study investigated the effect of a high-fat (HF) diet on protein expression
      of leptin and its receptor in the gonads of dams and their offspring. Female
      Wistar rats were fed a HF diet (30% fat) or a standard breeding (BD) diet (5%
      fat) during pregnancy and lactation. At 21 days of lactation, mothers and both
      sexes of prepubertal offspring were killed by decapitation. The protein
      expression of leptin and its receptor was assayed by Western blot and
      immunohistochemistry in gonadal, periovarian, and epididymal white adipose tissue
      (WAT). We demonstrated that leptin protein expression in ovary, and both leptin
      and ObRb expression in periovarian WAT was decreased in HF dams compared with BD
      animals. Immunohistochemistry showed lower leptin expression in growing antral
      follicles and corpora lutea of HF dams. Conversely, in both gonads and epididymal
      WAT of HF offspring, leptin and its receptor were significantly higher expressed
      compared with BD. Immunolocalization of leptin system in HF offspring gonads
      showed higher expression in growing and antral follicles of the ovary,
      seminiferous tubules, and interstitial tissue of testes. In conclusion, high
      gonadal and gonadal-WAT expression of leptin system was observed in the offspring
      of dams fed a HF diet during pregnancy and lactation.

PMID- 28759942
TI  - 11-Keto-beta-Boswellic Acid Inhibits Lymphocyte (CD3) Infiltration Into
      Pancreatic Islets of Young None Obese Diabetic (NOD) Mice.
AB  - 11-Keto-beta-Boswellic acid (KBA) has been shown to prevent infiltration of
      lymphocytes into pancreatic islets and appearance of peri-insular apoptotic cells
      in an animal model of autoimmune diabetes caused by injection of Multiple Low
      Doses of Streptozotocin (MLD-STZ), which is a chemical compound belonging to the
      class of nitrososureas. The aim of this work was to study whether or not KBA can
      also prevent/attenuate infiltration of lymphocytes into pancreatic islets and
      appearance of peri-insular apoptotic cells in an animal model of autoimmune
      diabetes caused by genetic dysfunction resembling human type 1 diabetes in
      several important features. Four weeks old female NOD mice received daily i.p.
      injections of 7.5 mg/kg of KBA over a period of 3 weeks. Compared to 4 weeks old
      animals there was significant infiltration of lymphocytes (CD3) into pancreatic
      islets and appearance of peri-insular apoptotic cells in the period between 4 and
      7 weeks. During this time plasma glucose dropped significantly and body weight
      did not increase. As far as pro-inflammatory cytokines are concerned, except a
      small increase of IFN-gamma, there was no change in the blood. In mice that had
      been treated with KBA between 4 and 7 weeks after birth no significant
      infiltration of lymphocytes into pancreatic islets and appearance of peri-insular
      apoptotic cells was observed, when compared to 4 weeks old mice. Moreover, there
      was no drop of blood glucose and the animals gained body weight. It is concluded
      that - similar to the model of MLD-STZ-diabetes - also in the NOD mouse model KBA
      is able to attenuate or even prevent development of insulitis, suggesting that
      KBA protects islets from autoimmune reaction regardless whether the signal is
      provided by a chemical compound or by genetic dysfunction. Whether this also
      holds for human type 1 diabetes remains to be established.

PMID- 28759943
TI  - The Effects of Vitamin D Supplementation on Glucose Metabolism and Lipid Profiles
      in Patients with Gestational Diabetes: A Systematic Review and Meta-Analysis of
      Randomized Controlled Trials.
AB  - This systematic review and meta-analysis of randomized controlled trials (RCTs)
      was conducted to summarize the effect of vitamin D supplementation on glucose
      homeostasis parameters and lipid profiles in gestational diabetes (GDM) patients.
      We conducted an electronic systematic search of MEDLINE, and 4 other research
      databases from inception to August 2016, in addition to performing hand searches
      and consulting with experts in the field. The index of heterogeneity between
      studies was determined using Cochran (Q) and I-squared tests. Given the existing
      heterogeneity between studies, a fix or random effect model was performed to
      estimate the standardized mean difference (SMD) for each variable by using
      inverse variance method and Cohen statistics. Six randomized clinical trials (187
      subjects and 184 controls) were included. The results showed that vitamin D
      supplementation significantly reduced the homeostasis model assessment of insulin
      resistance (HOMA-IR) [SMD -0.66; 95% confidence interval (CI), -1.14 to -0.18],
      homeostatic model assessment-B cell function (HOMA-B) (SMD -0.52; 95% CI, -0.79
      to -0.25), LDL-cholesterol levels (SMD -0.33; 95% CI, -0.58 to -0.07), and
      significantly increased quantitative insulin sensitivity check index (QUICKI)
      (SMD 0.73; 95% CI, 0.26 to 1.20). We found no beneficial effect of vitamin D
      supplementation on fasting plasma glucose (FPG), insulin, HbA1c, total-, HDL
      cholesterol, and triglycerides concentrations. In conclusion, this meta-analysis
      demonstrated that vitamin D supplementation may lead to an improvement in HOMA
      IR, QUICKI, and LDL-cholesterol levels, but did not affect FPG, insulin, HbA1c,
      triglycerides, total- and HDL-cholesterol levels; however, vitamin D
      supplementation increased HOMA-B.

PMID- 28759944
TI  - Impact of health utility after thrombotic complications following total hip and
      knee arthroplasty.
AB  - BACKGROUND: Medical complications and preexisting conditions frequently place the
      surgeon in the unenviable position of choosing between the serious and
      potentially life-threatening effects of thrombosis, or the issue of bleeding and
      surgical site complications. The aim of this research was to determine if health
      utility could be a consideration before choosing to therapeutically anticoagulate
      in the hip and knee arthroplasty patient. METHODS: The quantitative risks and
      effectiveness of treatment options for venous thromboembolism, atrial
      fibrillation, acute coronary syndromes, ischaemic stroke and mechanical heart
      valves were evaluated from previously published data. Previously calculated
      health utility values were obtained from published studies for both thrombotic
      events and anticoagulant-related complications at the site of arthroplasty. An
      impact score was generated through a multiplication of 1 - utility with the rate
      of the event occurring. RESULTS: Impact scores associated with revision surgery
      and deep infection at the arthroplasty site following anticoagulation are higher
      compared to impact scores in subsets of non-treated venous thromboembolism, low
      CHADS2 (congestive heart failure, hypertension, age >75, diabetes (1 point each),
      stroke/transient ischaemic attack (2 points)) atrial fibrillation and potentially
      some acute coronary syndrome patients. Some anticoagulation strategies in
      mechanical heart valves are of definite overall patient value due to the
      significant complications otherwise. CONCLUSION: Objective calculation of both
      the benefit and risks of anticoagulation in the post-operative patient is
      significantly altered by including the effect on patient's quality of life
      utility value. Therapeutic anticoagulation in some common situations is probable
      to be of more detriment than benefit when considering health utility.

PMID- 28759945
TI  - Scotopic contrast sensitivity and glare after accelerated corneal cross-linking.
AB  - BACKGROUND: The aim was to assess one-year changes in uncorrected and corrected
      contrast sensitivity (CS) and glare under scotopic conditions after accelerated
      cross-linking (CXL) using the 18 mW/cm2 protocol for the treatment of progressive
      keratoconus and compare results with unoperated controls. METHODS: In this non
      randomised clinical trial, 30 eyes were enrolled in the CXL group and 30 were
      assigned to the control group. Scotopic CS at spatial frequencies (SFs) of 0.5,
      1.1, 2.2, 3.4, 7.1 and 15 cycles per degree (cpd) were assessed using the
      MonCv3System (Metrovision, Perenchies, France) under scotopic conditions (0.5
      lux) at baseline and at six and 12 months. RESULTS: The mean ages of the
      participants in the CXL and control groups were 24.32 +/- 5.17 and 30.93 +/- 7.43
      years, respectively (p < 0.001). After adjusting for age, changes in uncorrected
      and corrected CS and glare were similar in the two groups (all p > 0.05) except
      for corrected CS at SF 7.1 cpd (1.45 +/- 4.31 versus 3.21 +/- 4.69 dB, p = 0.010)
      and 15 cpd (1.12 +/- 4.63 versus 3.03 +/- 5.48 dB, p = 0.007), which were reduced
      as an effect of CXL. Based on covariate analyses, among corrected CS indices,
      corrected CS7.1 and CS15 were related to CXL and their baseline values (all p <
      0.050). Uncorrected CS in all SFs and uncorrected and corrected glare were
      related to their pre-operative values (all p < 0.001). CONCLUSION: Accelerated
      CXL can reduce scotopic corrected CS at SFs higher than 7.0 cpd in cases with
      better baseline values of these parameters. Changes in uncorrected CS and glare
      are only a factor of baseline values and the indices reduce in cases with better
      baseline values after one year.

PMID- 28759946
TI  - Which age-adjusted D-dimer cut-off performs best?

PMID- 28759947
TI  - Paediatric surgical services in remote northern Australia: an integrated model of
      care.
AB  - BACKGROUND: Surgical services for children in the Northern Territory of Australia
      are routinely performed by general surgeons with specific paediatric training,
      supported by paediatric surgeons. In Australasia, indications for appropriate
      transfer of elective routine surgery in children to tertiary paediatric surgical
      centres have been contentious. To transfer all elective paediatric cases from
      rural locations would have significant social and financial consequences for
      families and the health system. This study reviews clinical outcomes for elective
      surgery for two common conditions managed by an integrated service of general
      surgeons and visiting paediatric surgeons, and compares them with published
      outcomes from paediatric centres. METHOD: A retrospective audit of children
      undergoing orchidopexy under the age of 5 years or inguinal herniotomy under the
      age of 1 year at the Royal Darwin Hospital and Darwin Private Hospital between
      January 2005 and 2016 was conducted. RESULTS: During the study period, 66 boys
      underwent 80 orchidopexies at a mean age of 22.3 months (+/-20.4 SD). A
      recurrence rate of 5.5%, severe atrophy rate of 1.3% and total atrophy rate of
      5.5% were achieved. Sixty-three children underwent 65 inguinal herniotomies at a
      mean age of 2.5 months (+/-4.2). A testicular maldescention and atrophy rate of
      1.8% and recurrence rate of 0% was achieved. CONCLUSION: Children managed with
      this model of care had complication rates equivalent to or slightly higher than
      published gold standards. Considering the family disruption, cultural, financial
      implications and threat to compliance that transfer across vast distances
      entails, this model provides acceptable outcomes.

PMID- 28759948
TI  - The role of epidural contrast distribution in predicting the effectiveness of
      steroid and local anesthetic injection in patients with lumbar spinal stenosis.
AB  - STUDY DESIGN: A prospective observational comparative study. BACKGROUND: Because
      epidural corticosteroids are more effective for pain relief when delivered close
      to the site of pathology, lumbar spinal stenosis with multilevel stenotic areas
      can be treated more effectively when medications cover all of the stenotic areas.
      Distribution of medications to the pathologic sites is considered an important
      factor in the effectiveness of inter-laminar epidural injection. OBJECTIVE: To
      determine whether spread of a lidocaine and triamcinolone mixture over the
      stenotic areas improves clinical symptom of spinal stenosis more effectively.
      METHODS: Twenty-four patients with lumbar spinal stenosis were enrolled in this
      study. A lumbar inter-laminar epidural injection under fluoroscopic guidance was
      administered to each patient. A numeric rating scale (NRS), claudication
      distance, the Romberg test, and the Oswestry Disability Index (ODI) were checked
      pre-injection and at 2, 6, and 12 weeks after the epidural injection. Vertebrae
      that showed more than moderate stenosis were considered stenosis levels. Inter
      laminar epidural injection was performed with radiopaque contrast and lidocaine
      mixed with triamcinolone acetate. When the contrast covered all of the stenosis
      levels, this was considered a sufficient distribution (SD) and when the contrast
      did not cover all stenosis levels, this was considered an insufficient
      distribution (ID). RESULTS: At 2 weeks, percentages of NRS improvement were 71.4
      (IQR, 20.2) in SD group and 50.0 (IQR, 31.4) in ID group (P= 0.02), changes in
      Romberg test time were 0.0 (IQR, 35.0) in SD group and -3.0 (IQR, 12.0) in ID
      group (P= 0.02), decreases in ODI were 9.6 (IQR, 11.2) in SD group and 0.0 (IQR,
      7.8) in ID group (P= 0.02). However, these parameters were not significantly
      different at 6 weeks and 12 weeks. Claudication distance showed no significant
      group difference. CONCLUSION: Coverage of the stenotic area by the lidocaine,
      triamcinolone, and contrast dye mixture during inter-laminar epidural injection
      was an important predictor of acute pain reduction.

PMID- 28759949
TI  - Is saphenous nerve radio frequency an effective treatment for advanced
      gonarthrosis in elders with cardiac comorbidity?
AB  - BACKGROUND: Pulsed radiofrequency (PRF) used for knee pain originating from
      osteoarthritis is one of these methods. OBJECTIVES: The aim of the study was to
      evaluate the knee functional status and pain palliation following the application
      of pulse radiofrequency in patients with cardiac comorbid disease who were
      diagnosed with advanced stage osteoarthritis. METHODS: Thirty-eight patients with
      high surgical risk having cardiac comorbidities with grade 3-4 gonarthrosis
      according to the Kellgren-Lawrence classification were retrospectively analyzed.
      PRF was applied to the saphenous nerve of each patient. Visual Analog Scale for
      knee pain evaluation both at rest and on movement and the Lysholm Knee Scoring
      Scale for function evaluation were used. The patient status was evaluated before
      the procedure and at the first and sixth months after the procedure. RESULTS: The
      mean age was 68.8 years (range, 53-82 years). Both the rest and movement post
      procedural Visual Analog Scale scores at first and sixth months were
      significantly lower than pre-procedural values (p< 0.001). A statistically
      significant improvement was also determined when pre- and one and six months post
      procedural Lysholm scores were compared (p< 0.001). CONCLUSIONS: PRF is a safe
      and function sparing minimally invasive pain palliation method for knee
      osteoarthritis in elders with cardiac comorbidity.

PMID- 28759950
TI  - Chemokine receptor CXCR7 is an independent prognostic biomarker in glioblastoma.
AB  - BACKGROUND: Glioblastoma (GBM) is the most common and most fatal primary brain
      cancer in adults. Due to the complex nature of GBM, its pathogenesis still remain
      unclear. Accumulating evidence suggest that chemokine receptor CXCR7 contribute
      to the development of various types of tumors. OBJECTIVE: We aim to examine the
      prognostic significance of CXCR7 in GBM. METHODS: CXCR7 were first detected by
      Immunohistochemistry. The association between CXCR7 and overall survival (OS)
      were examined. Moreover, multivariate analyses were conducted to evaluate the
      prognostic factors in GBM. RESULTS: Of all 146 GBM patients recruited, 77 were in
      the high-expression subgroup, the rest 69 were in low-expression subgroup. There
      are no differences between these two subgroups in terms of age, gender, family
      history of cancer, extent of surgery, chemotherapy, radiotherapy, KPS, MGMT
      methylation status and tumor size. However, high CXCR7 expression was robustly
      correlated with poor OS in GBM. Multivariate analysis confirmed age, KPS scores,
      chemotherapy, IDH1 mutation, MGMT methylation and CXCR7 were independent factors
      in survival prognosis. CONCLUSIONS: CXCR7 may involve in the clinical GBM
      progression, and CXCR7 could be a valuable prognostic marker in the treatment of
      GBM.

PMID- 28759951
TI  - Promoter hypermethylation of RAR-beta tumor suppressor gene in gastric carcinoma:
      Association with histological type and clinical outcomes.
AB  - BACKGROUND: While gastric cancer is a common cancer in the world and Iran, its
      molecular mechanisms are not fully understood as yet. Epigenetic modifications
      can lead to alteration of gene expression and development of tumorigenesis
      mechanisms. METHODS: To clarify the difference in DNA methylation pattern of
      histological types in gastric carcinoma, CpG islands in the promoters of retinoic
      acid receptor beta gene (RAR-beta) was studied using methylation-specific PCR.
      RESULTS: In gastric cancer tissues, hypermethylation frequency of RAR-beta gene
      was respectively 61 and 33% for diffuse and intestinal type. In diffuse type,
      hypermethylation of RAR-beta has been significantly associated with invasion (P=
      0.007), differentiation (P= 0.033) and location (P= 0.012) of the tumor. However,
      hypermethylation of RAR-beta correlated only with tumor size (P= 0.029) in
      intestinal type. For adjacent non-tumor samples, hypermethylation of RAR-beta was
      not detected and there was no significant association between age of diagnosis
      and hypermethylation of RAR-beta in both types of gastric cancer. CONCLUSIONS:
      These results support previous findings denoting a distinct profile of promoter
      hypermethylation status in the development of the intestinal and diffuse type of
      gastric carcinoma and the process of the tumorigenesis in these subtypes of
      gastric cancer is different from each other.

PMID- 28759952
TI  - Expression and genetic polymorphism of necroptosis related protein RIPK1 is
      correlated with severe hepatic ischemia-reperfusion injury and prognosis after
      hepatectomy in hepatocellular carcinoma patients.
AB  - OBJECTIVES: The goal of our study was to assess the prognostic impact of the
      necroptosis relative protein RIPK1 genetic polymorphism in ischemia-reperfusion
      injury and survival after hepatectomy in hepatocellular carcinoma (HCC) patients.
      METHODS: In this study, expression of RIPK1 and its genetic
      polymorphism(rs2272990) were examined in plasma of 44 HCC patients. All these
      patients were undergoing partial hepatectomy. The prognostic values of RIPK1
      genetic polymorphism for tumor development and survival, and ischemia-reperfusion
      injury after hepatectomy were further determined. RESULTS: Plasma RIPK1
      expressions were significantly increased in HCC patients, compared to the healthy
      control group. Totally 19 patients have the GA + AA genotype in the RIPK1
      rs2272990 SNP site and 25 have GG genotype. There were no statistically
      significant intergroup differences observed in age, gender, AFP value, HBV
      positive, tumor size or cirrhosis. GG genotype had positive correlation with TNM
      classification (p= 0.033) and lymphatic metastasis (p= 0.027) and was
      significantly associated with severe hepatic ischemia-reperfusion injury and
      decreased survival rate after hepatectomy. CONCLUSION: In conclusion, the RIPK1
      polymorphism is an indicator of hepatic injury and a novel prognostic biomarker
      for tumor development and survival of HCC recipients after hepatectomy.

PMID- 28759953
TI  - Nicotine cut-off value in human hair as a tool to distinguish active from passive
      smokers: A cross-sectional study in Japanese men.
AB  - BACKGROUND: Nicotine concentration in hair is a useful marker of tobacco
      exposure. Detection of nicotine in the hair of non-smokers indicates passive
      smoking. Accurate measurement of nicotine among active and passive smokers can
      help in smoking cessation programs or programs designed to prevent secondhand
      smoke exposure. OBJECTIVE: To establish, using high-performance liquid
      chromatography-ultraviolet detection (HPLC/UV), a hair nicotine cut-off value to
      distinguish active from passive smokers. METHODS: Hair samples were collected
      from randomly chosen Japanese men (n= 192) between 2009 and 2011. Nicotine and
      cotinine levels in hair were measured using HPLC/UV with column-switching. T
      tests and chi-square tests were performed to compare active and passive smokers,
      while receiver operating characteristic curves were used to evaluate the
      effectiveness of the cut-off value. RESULTS: There were 69 active smokers and 123
      passive smokers. The nicotine and cotinine concentrations in hair were
      significantly higher in active than in passive smokers (p< 0.01). The area under
      the curve for nicotine was 0.92. A hair nicotine cut-off value of 5.68 ng/mg,
      with a sensitivity of 94.2% and specificity of 87.0%, was identified as the
      optimal cut-off value for separating active from passive smokers. CONCLUSION:
      Nicotine and cotinine concentrations in hair clearly distinguished active from
      passive smokers.

PMID- 28759954
TI  - Prognostic significance of the genetic and the immunohistochemical expression of
      epithelial-mesenchymal-related markers in colon cancer.
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) is one of the main events in
      colorectal cancer (CRC) spread. Snail-1 is a zinc transcription factor that
      mediates EMT in tumor cells probably by down-regulation of E-cadherin and claudin
      1. OBJECTIVES: To detect the expression of epithelial markers (claudin-1 and E
      cadherin) and mesenchymal markers (snail-1 and vimentin) in primary cancer colon.
      Also, to select stage II cancer patients of a high risk that can benefit from
      postoperative adjuvant chemotherapy. METHODS: Reverse transcription-polymerase
      chain reaction (RT-PCR) and immunohistochemical analysis were performed to
      investigate snail-1, claudin-1, E-cadherin and vimentin expressions at mRNA and
      protein levels in fresh tissues of cancer colon and normal colonic mucosa. The
      correlations between the expression of these markers and clinicopathological
      parameters were performed. RESULTS: Normal colonic mucosa revealed complete
      membranous expression of claudin-1, preserved E-cadherin and negative snail-1 and
      vimentin expressions. Compared to control, the expression of snail-1 and vimentin
      mRNA in cancer colon was significantly up-regulated while the expression of
      claudin-1 and E-cadherin mRNA was significantly down-regulated. These changes
      were significantly associated with stage and lymph node involvement at both mRNA
      and protein levels (p< 0.05). There were significant negative correlations
      between vimentin and each of E-cadherin and claudin-1 gene expression and between
      snail-1 and each of E-cadherin and claudin-1 gene expression. Moreover, these
      changes were independent predictors of recurrence of stage II cancer colon cases.
      CONCLUSION: There is a clinical significance of snail-1, claudin-1, E-cadherin
      and vimentin as possible markers for recognizing patients with lymph node
      involvement, advanced stage and high incidence of tumor recurrence in cancer
      colon.

PMID- 28759955
TI  - Downregulation of miR-138 predicts poor prognosis in patients with esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: MicroRNAs (miRNAs) have been proven to be critical players in many
      different types of tumors including esophageal squamous cell carcinoma (ESCC).
      OBJECTIVE: This study aimed at investigating the correlation of miR-138
      expression and clinical outcome of patients with ESCC. METHODS: A total of 168
      serum samples and 128 fresh cancer tissues as well as their corresponding
      adjacent non-cancerous tissues were collected. Real-time PCR was performed to
      evaluate the clinical value of miR-138 in ESCC. RESULTS: Our results showed that
      tissue and serum miR-138 levels were both significantly reduced in ESCC compared
      to their respective controls. Tissue miR-138 levels were highly correlated with
      serum miR-138 levels. Serum miR-138 differentiated patients with ESCC from
      healthy controls with high accuracy. In addition, reduced tissue/serum miR-138
      levels were correlated with unfavorable clinicopathological parameters including
      T stage, lymph node metastasis and TNM stage. ESCC patients with lower
      tissue/serum miR-138 levels had shorter five year overall survival compared with
      those with higher tissue/serum miR-138 levels. Finally, downregulation of miR-138
      was demonstrated to be an independent prognostic risk factor for ESCC.
      CONCLUSIONS: In conclusion, both tissue and serum miR-138 levels are reduced in
      ESCC, and might be promising prognostic biomarkers for ESCC.

PMID- 28759956
TI  - Long non-coding RNA Fer-1-like protein 4 acts as a tumor suppressor via miR-106a
      5p and predicts good prognosis in hepatocellular carcinoma.
AB  - Long non-coding RNAs (lncRNAs) are aberrantly expressed in various cancers. Fer-1
      like protein 4 (FER1L4), one of lncRNAs, plays a role as tumor suppressor in
      various human cancers and can be regulated by microRNA. However, the role and
      function of FER1L4 in human hepatocellular carcinoma (HCC) remains unknown. The
      aim of the present study was to annotate the role of FER1L4 and its clinical
      value in HCC. In the present study, we found that FER1L4 was lowly expressed in
      HCC tissue specimens as well as in malignant HCC cell lines, while the situation
      is opposite in miR-106a-5p. We found that down-regulated FER1L4 increased the
      expression of miR-106a-5p significantly and there was a reciprocal repression
      between FER1L4 and miR-106a-5p. Moreover, we identified FER1L4 as a target of miR
      106a-5p by using dual-luciferase reporter assay. Knockdown of FER1L4 promoted the
      malignancy of HCC cells, including proliferation, migration, and invasion, and
      inhibited cell apoptosis. We also found that FER1L4 functions as a tumor
      suppressor in vivo. Together, these results suggest that FER1L4 could exert a
      tumor suppressive impact on HCC, which at least, in part, through suppressing miR
      106a-5p expression. FER1L4, as well as miR-106a-5p, can predict the clinical
      prognosis of HCC alone or combined, which may be a novel therapeutic target for
      treating HCC.

PMID- 28759957
TI  - Down-regulated long non-coding RNA SNHG1 inhibits tumor genesis of colorectal
      carcinoma.
AB  - BACKGROUND: Colorectal carcinoma (CRC) is the vital cancer mortality worldwide
      and the long noncoding RNAs (lncRNAs) is considered as an important biomarker.
      The aim of this study was to examine the influence of lncRNA-SNHG1in CRC, and
      explore the relationship of lncRNA-SNHG1 and CRC, and consequently find a new
      therapeutic target for CRC patients. METHODS: This study used 80 CRC patients and
      several cancer cell lines, with RNA interference technology to find the function
      of SNHG1. RESULTS: SNHG1 expression was higher in CRC tissue lines other than the
      cancer adjacent tissues. Moreover, down-regulated SNHG1 resulting in smaller
      tumor size and lighter tumor weight. Additionally, down-regulated SNHG1 inhibited
      cell migration, proliferation and colony formation, but promoted cell apoptosis.
      CONCLUSION: Our findings revealed that down-regulated SNHG1 could inhibit CRC
      tumor genesis and SNHG1 might act as an important potential therapeutic target in
      CRC treatment.

PMID- 28759958
TI  - Observation of significant biomarkers in osteosarcoma via integrating module-
      identification method with attract.
AB  - OBJECTIVE: Osteosarcoma (OS) is the most frequent type of bone malignancy, and
      this disease has a poor prognosis. We aimed to identify the significant genes
      related with OS by integrating module-identification method and attract approach.
      METHODS: OS-related microarray data E-GEOD-36001 were obtained from ArrayExpress
      database, and then protein-protein interaction (PPI) networks of normal and OS
      were re-weighted by means of spearman correlation coefficient (SCC). Next,
      maximal cliques were detected from the re-weighted PPI networks using
      clusteringbased on maximal cliques approach. Afterwards, highly overlapped
      cliques were merged according to the interconnectivity, following by candidate
      modules and seed modules identification. Attract proposed by Mar et al. who have
      suggested that this approach can extract and annotate the gene-sets which can
      distinguish between disease and control samples, and obtained differences of
      these gene-sets among the expression profile of samples were defined as
      attractors. Thus, we applied attract method to extract differential modules from
      the seed modules, and these obtained differential modules were defined as
      attractors. The genes in attractors were determined as attractor genes. RESULTS:
      After eliminating the maximal cliques with nodes less than 4, there were 1,884
      and 528 maximal cliques in normal and OS PPI networks, which were used to conduct
      module analysis. A total of 60 and 19 candidate modules were obtained in control
      and OS PPI networks, respectively. By comparing with normal group, 2 seed module
      pairs with similar gene composition were found. Significantly, based on attract
      method, we found that these 2 modules were differential. These 2 modules had the
      same gene size with 4 genes. Of note, genes CCNB1 and KIF11 simultaneously
      appeared in these two attractors. CONCLUSIONS: We successfully identified two
      attractors via integrating module-identification method and attract approach, and
      attractor genes, for example, CCNB1 and KIF11 might play pathophysiological roles
      in OS development and progression.

PMID- 28759959
TI  - Low serum miR-373 predicts poor prognosis in patients with pancreatic cancer.
AB  - BACKGROUND: Circulating microRNAs (miRNAs) are emerging as novel biomarkers for
      various types of cancer including pancreatic cancer (PC). OBJECTIVE: We aimed to
      explore the diagnostic and prognostic significance of serum miR-373 in PC.
      METHODS: In the current study, we recruited a total of 103 PC patients, 30
      patients with benign pancreatic tumor, 20 patients with chronic pancreatitis and
      50 healthy volunteers. Total RNA was isolated from all the blood samples, and
      relative miR-373 expression levels were detected by reverse transcription
      quantitative polymerase chain reaction (RT-qPCR). RESULTS: Our findings
      demonstrated that serum miR-373 expression was greatly down-regulated in PC
      patients. The area under the receiver-operating characteristic (ROC) curve (AUC)
      for serum miR-373 was 0.852 for discriminating PC patients from normal control
      subjects. In addition, a positive correlation was observed between reduced serum
      miR-373 level and several clinical parameters, including TNM stage, lymph node
      metastasis and distant metastasis. Moreover, PC patients with lower serum miR-373
      level had shorter 5 year overall survival. Finally, serum miR-373 was proved to
      be an independent predictor for PC. CONCLUSIONS: Taken together, serum miR-373
      might serve as a promising biomarker for the early detection and prognosis
      prediction of PC.

PMID- 28759960
TI  - Low expression of NEK2 is associated with hepatocellular carcinoma progression
      and poor prognosis.
AB  - BACKGROUND: NIMA-related kinase 2 (NEK2), a serine/threonine kinase, is located
      in the centrosome and is a member of cell cycle regulation related protein kinase
      (CCRK) family. Aberrant expression of NEK2 is linked with carcinogenesis and
      progression of various tumors. OBJECTIVE: To investigate the expression level of
      NEK2 and its relationship with clinicopathological factors in hepatocellular
      carcinoma (HCC). METHODS: Immunohistochemistry was used to measure the expression
      of NEK2 in 310 patients' specimen tissues and 197 adjacent normal liver tissues
      of HCC cases, and the subsequent prognostic value for each sample was estimated.
      RESULTS: NEK2 expression levels in HCC were lower than in adjacent tissues (49.7%
      vs. 72.6%, P< 0.001). First, patients with relatively low NEK2 expression had
      increased cancer progression and poorer prognosis than those with high
      expression. Second, NEK2 expression was significantly reduced in patients with
      large tumors (P= 0.025), with stage III Edmondson-Steiner Grading (P= 0.015).
      Third, patients' tumor size positively correlated with high AFP concentration (P=
      0.017). Fourth, using the Kaplan-Meier survival curve, we found a lower survival
      rate in patients with decreased expression of NEK2 than those with high NEK2
      expression in HCC (P= 0.029, Log-rank test). CONCLUSIONS: Low NEK2 expression
      might be a useful predictor in HCC as a poor prognostic factor, and could serve
      as a potential therapeutic target for HCC.

PMID- 28759961
TI  - Lumbar sympathectomy regulates vascular cell turnover in rat hindfoot plantar
      skin.
AB  - BACKGROUND: Sympathetic denervation and impaired angiogenesis cause skin
      diseases. However, the relationship between the sympathetic nervous system and
      vascular cell turnover in normal skin remains unclear. OBJECTIVE: To determine
      the effects of sympathetic denervation on vascular cell turnover in normal skin.
      METHODS: Rats underwent bilateral L2-4 sympathetic trunk resection (sympathectomy
      group) or sham operation (control). Hindfoot plantar skin was analyzed 2 weeks
      and 3 months postoperatively. RESULTS: Mural cell marker (alpha-smooth muscle
      actin; p < 0.001, and desmin; p = 0.047) expression decreased 2 weeks after
      sympathectomy, but recovered 3 months after sympathectomy (p > 0.05). CD31 levels
      were lower in the experimental group than in the control group at 2 weeks (p =
      0.009), but not at 3 months. Von Willebrand factor, vascular endothelial growth
      factor, and angiopoietin-2 expression were not significantly different between
      the groups (p > 0.05). Angiopoietin-1 expression levels were higher in the
      experimental group than in the control group at 2 weeks (p = 0.035), but not at 3
      months. CONCLUSIONS: Lumbar sympathectomy regulates vascular cell turnover in rat
      hindfoot plantar skin by inhibiting mural cell proliferation and increasing
      angiopoietin-1 expression. Sympathetic nerves therefore play an important role in
      plantar skin vascular cell turnover.

PMID- 28759962
TI  - Effects of hydroxyurea on blood rheology in sickle cell anemia: A two-years
      follow-up study.
AB  - The aim of the present study was to test the effects of hydroxyurea (HU) therapy
      on clinical, hematological and hemorheological parameters in adult patients with
      sickle cell anemia (SCA). Hematological and hemorheological parameters were
      measured in 28 SCA patients before HU therapy (i.e., baseline) and at 6, 12 and
      24 months of treatment. RBC deformability was determined by ektacytometry at 30
      Pa. RBC aggregation properties were investigated by light-backscatter method.
      Blood viscosity was measured at 225 s-1 by a cone-plate viscometer. The rates of
      vaso-occlusive crises and acute chest syndrome were lower at 1 and 2 years of HU
      therapy compared to baseline. The proportion of patients with leg ulcers tended
      to decrease after 2 years of treatment. Hemoglobin oxygen saturation improved
      with HU therapy. HU therapy induced a decrease of platelet and white blood cell
      counts and a rise in fetal hemoglobin level and mean cell volume. While
      hemoglobin concentrations increased under HU, blood viscosity remained unchanged
      all along the study. RBC deformability increased over baseline values at 6 months
      of HU therapy and continued to rise until the end of the follow-up period. In
      conclusion, the improvement in RBC deformability probably compensates the
      increase of hemoglobin on blood viscosity and participates to the improvement of
      the clinical status of patients.

PMID- 28759963
TI  - Nondiagnostic cytological results on ultrasound-guided fine needle aspiration:
      Does the thyroid nodule depth matter?
AB  - OBJECTIVE: To evaluate whether thyroid nodule depth and other ultrasound features
      can predict nondiagnostic cytological results on ultrasound-guided fine needle
      aspiration. MATERIAL AND METHODS: This retrospective study included 412 thyroid
      nodules that underwent ultrasound-guided fine needle aspiration from 2014 to
      2015. The nodules were classified as nondiagnostic and diagnostic by the
      cytopathological results. Clinical information of the patients (ie., age, sex)
      and ultrasound features (ie., size, depth, calcification, cystic content,
      vascularity) of the nodules were recorded and compared between the nondiagnostic
      group and diagnostic group. RESULTS: Age and sex were not significantly different
      between the nondiagnostic group and diagnostic group (P > 0.05). Nodule depth >15
      mm (OR, 7.128; P < 0.001), peripheral rim calcification (OR, 5.725; P = 0.01) and
      cystic content >50% (OR, 2.995; P = 0.018) were factors for the nondiagnostic
      ultrasound-guided fine needle aspiration cytopathological results.
      Macrocalcification in the nodule sized 5-10 mm was associated with the
      nondiagnostic results (P = 0.04). Nodule size and vascularity were not associated
      with the nondiagnostic results (P > 0.05). CONCLUSIONS: Nodule depth >15 mm,
      peripheral rim calcification and cystic content >50% were three independent
      predictors of the nondiagnostic cytopathological results. Macrocalcification in
      the nodule sized 5-10 mm was also associated with the nondiagnostic results.

PMID- 28759964
TI  - Extracorporeal perfusion - reduced to a one-way infusion.
AB  - BACKGROUND: Extracorporeal perfusion (EP) is moving into focus of research in
      reconstructive and transplantation medicine for the preservation of amputates and
      free tissue transplants. The idea behind EP is the reduction of ischemia-related
      cell damage between separation from blood circulation and reanastomosis of the
      transplant. Most experimental approaches are based on a complex system that moves
      the perfusate in a circular course. OBJECTIVE AND METHODS: In this study, we
      aimed to evaluate if a simple perfusion by an infusion bag filled with an
      electrolyte solution can provide acceptable results in terms of flow stability,
      oxygen supply and viability conservation for EP of a muscle transplant. The
      results are compared to muscles perfused with a pump system as well as muscles
      stored under ischemic conditions with a one-time intravasal flushing with
      Jonosteril. RESULTS: With this simple method a sufficient oxygen supply could be
      achieved and functionality could be maintained between 3.35 times and 4.60 times
      longer compared to the control group. Annexin V positive nuclei, indicating
      apoptosis, increased by 9.7% in the perfused group compared to 24.4% in the
      control group. CONCLUSIONS: Overall, by decreasing the complexity of the system,
      EP by one-way infusion can become more feasible in clinical situations.

PMID- 28759965
TI  - Sensing of Alzheimer's Disease and Multiple Sclerosis Using Nano-Bio Interfaces.
AB  - It is well understood that patients with different diseases may have a variety of
      specific proteins (e.g., type, amount, and configuration) in their plasmas. When
      nanoparticles (NPs) are exposed to these plasmas, the resulting coronas may
      incorporate some of the disease-specific proteins. Using gold (Au) NPs with
      different surface properties and corona composition, we have developed a
      technology for the discrimination and detection of two neurodegenerative
      diseases, Alzheimer's disease (AD) and multiple sclerosis (MS). Applying a
      variety of techniques, including UV-visible spectra, colorimetric response
      analyses and liquid chromatography-tandem mass spectrometry, we found the corona
      NP complexes, obtained from different human serums, had distinct protein
      composition, including some specific proteins that are known as AD and MS
      biomarkers. The colorimetric responses, analyzed by chemometrics and statistical
      methods, demonstrate promising capabilities of the technology to unambiguously
      identify and discriminate AD and MS. The developed colorimetric technology might
      enable a simple, inexpensive and rapid detection/discrimination of
      neurodegenerative diseases.

PMID- 28759966
TI  - Trajectories of Multidimensional Caregiver Burden in Chinese Informal Caregivers
      for Dementia: Evidence from Exploratory and Confirmatory Factor Analysis of the
      Zarit Burden Interview.
AB  - BACKGROUND: Despite its popularity, the latent structure of 22-item Zarit Burden
      Interview (ZBI) remains unclear. There has been no study exploring how caregiver
      multidimensional burden changed. OBJECTIVE: The aim of the work was to validate
      the latent structure of ZBI and to investigate how multidimensional burden
      evolves with increasing global burden. METHODS: We studied 1,132 dyads of
      dementia patients and their informal caregivers. The caregivers completed the ZBI
      and a questionnaire regarding caregiving. The total sample was randomly split
      into two equal subsamples. Exploratory factor analysis (EFA) was performed in the
      first subsample. In the second subsample, confirmatory factor analysis (CFA) was
      conducted to validate models generated from EFA. The mean of weighted factor
      score was calculated to assess the change of dimension burden against the
      increasing ZBI total score. RESULTS: The result of EFA and CFA supported that a
      five-factor structure, including role strain, personal strain, incompetency,
      dependency, and guilt, had the best goodness-of-fit. The trajectories of
      multidimensional burden suggested that three different dimensions (guilt, role
      strain and personal strain) became the main subtype of burden in sequence as the
      ZBI total score increased from mild to moderate. Factor dependency contributed
      prominently to the total burden in severe stage. CONCLUSION: The five-factor ZBI
      is a psychometrically robust measure for assessing multidimensional burden in
      Chinese caregivers. The changes of multidimensional burden have deepened our
      understanding of the psychological characteristics of caregiving beyond a single
      total score and may be useful for developing interventions to reduce caregiver
      burden.

PMID- 28759967
TI  - People with Dementia Can Learn Compensatory Movement Maneuvers for the Sit-to
      Stand Task: A Randomized Controlled Trial.
AB  - BACKGROUND: A complex motor skill highly relevant to mobility in everyday life
      (e.g., sit-to-stand [STS] transfer) has not yet been addressed in studies on
      motor learning in people with dementia (PwD). OBJECTIVE: To determine whether a
      dementia-specific motor learning exercise program enables PwD to learn
      compensatory STS maneuvers commonly taught in geriatric rehabilitation therapy to
      enhance patients' STS ability. METHODS: Ninety-seven patients with mild-to
      moderate dementia (Mini-Mental State Examination: 21.9+/-2.9 points) participated
      in a double-blinded, randomized, placebo-controlled trial with 10-week
      intervention and 3-month follow-up period. The intervention group (IG, n = 51)
      underwent a motor learning exercise program on compensatory STS maneuvers
      specifically designed for PwD. The control group (CG, n = 46) performed a low
      intensity motor placebo activity. Primary outcomes were scores of the Assessment
      of Compensatory Sit-to-stand Maneuvers in People with Dementia (ACSID), which
      covers the number of recalled and initiated, and of effectively performed
      compensatory STS maneuvers. Secondary outcomes included temporal and kinematic
      STS characteristics measured by a body-fixed motion sensor (BFS, DynaPort(r)
      Hybrid). RESULTS: The IG significantly improved in all ACSID scores compared to
      the CG (p < 0.001). Secondary analysis confirmed learning effects for all BFS
      based outcomes (p < 0.001-0.006). Learning gains were sustained during follow-up
      for most outcomes. CONCLUSION: People with mild-to-moderate dementia can learn
      and retain compensatory STS maneuvers in response to a dementia-specific motor
      learning exercise program. This is the first study that demonstrated preserved
      motor learning abilities in PwD by using a motor skill highly relevant to
      everyday life.

PMID- 28759970
TI  - A Novel Assessment and Profiling of Multidimensional Apathy in Alzheimer's
      Disease.
AB  - BACKGROUND: Apathy is a complex multidimensional syndrome frequently reported in
      Alzheimer's disease (AD) and is associated with impaired awareness. Here we
      present a psychometrically robust method to profile apathy in AD. OBJECTIVES: To
      determine the validity and reliability of a multidimensional apathy measure, the
      Dimensional Apathy Scale (DAS), and explore the apathy subtype profile and its
      associations in AD. METHODS: 102 people with AD and 55 healthy controls were
      recruited. Participants completed the DAS, the Apathy Evaluation Scale (AES),
      Geriatric Depression Short form (GDS-15), and Lawton Instrumental Activities of
      Daily Living (LIADL). Psychometric properties of the DAS were determined. AD
      Control comparison was performed to explore group differences on the DAS. Latent
      Class Analysis (LCA) was used to explore the profile of apathy in AD. RESULTS:
      The DAS had a good to excellent Cronbach's standardized alpha (self-rated = 0.85,
      informant/carer-rated = 0.93) and good convergent and divergent validity against
      standard apathy (AES) and depression (GDS-15) measures. Group comparison showed
      people with AD were significantly higher for all apathy subtypes than controls (p
      < 0.001), and lacking in awareness over all apathy subtype deficits. LCA showed
      three distinct AD subgroups, with 42.2% in the Executive-Initiation apathy, 28.4%
      in the Global apathy, and 29.4% in the Minimal apathy group. CONCLUSIONS: The DAS
      is a psychometrically robust method of assessing multidimensional apathy in AD.
      The apathy profiles in AD are heterogeneous, with additional specific impairments
      relating to awareness dependent on apathy subtype.

PMID- 28759969
TI  - Physical Activity in Midlife is not Associated with Cognitive Health in Later
      Life Among Cognitively Normal Older Adults.
AB  - BACKGROUND: Links between physical activity and dementia are based primarily on
      cross-sectional data or studies with unsatisfactory follow-up. OBJECTIVE: We
      leveraged three decades of follow-up from an established cohort to determine
      whether physical activity in midlife is associated with late-life cognition and
      dementia. METHODS: The Johns Hopkins Precursors study (n = 646) enrolled
      participants from 1948-1964 and administered questions about physical activity,
      from which we calculated metabolic equivalents (MET h/day), and exercise from
      1978-present. Cognitive tests were administered in 2008. Dementia was adjudicated
      through 2011. To characterize associations with midlife physical activity, we
      used linear regression for cognitive tests and Cox proportional hazards models
      for dementia onset. Models adjusted for age, sex, smoking, diabetes, and
      hypertension. RESULTS: No physical activity measure from 1978 was associated with
      late-life cognition or onset of dementia. Both MET h/day (beta= 0.007, 95% CI:
      0.002, 0.013) and regular exercise (beta= 0.357, 95% CI: 0.202, 0.513) in 2006,
      however, were associated with better cognition in 2008. CONCLUSION: Findings from
      this 30-year cohort study that physical activity measured recently, but not in
      mid-life, is associated with late-life cognition fits with null findings from
      randomized trials and other observational studies with extensive follow-up. Cross
      sectional findings may be misleading due to reverse causation.

PMID- 28759971
TI  - Validity of a Newly Developed Measure of Memory: Feasibility Study of the Virtual
      Environment Grocery Store.
AB  - Virtual reality-based neuropsychological assessments proffer the potential to
      address the limited ecological validity of pen-and-paper measures of memory. To
      investigate the construct validity of a newly developed virtual reality measure
      of memory, the Virtual Environment Grocery Store (VEGS), traditional
      neuropsychological measures of memory and executive functioning were administered
      to 48 older adults and 55 young adults. Performances on the VEGS memory tasks and
      the traditional neuropsychological assessments of memory were positively
      correlated, indicating that memory for VEGS content was similar to memory for
      traditional paper-and-pencil measures. The older adults performed significantly
      worse than young adults on the VEGS and the California Verbal Learning Test, but
      the DKEFS Color-Word Interference failed to differentiate the groups.
      Furthermore, significant differences were found between groups for the VEGS
      memory and multitasking measures. The VEGS has the advantage over traditional
      measures of providing objective measurement of individual components of memory in
      simulations of everyday activities.

PMID- 28759972
TI  - Molecular Mechanisms Underlying Neuroprotective Effect of Intranasal
      Administration of Human Hsp70 in Mouse Model of Alzheimer's Disease.
AB  - Heat shock protein 70, encoded by the HSPA1A gene in humans, is a key component
      of the machinery that protects neuronal cells from various stress conditions and
      whose production significantly declines during the course of aging and as a
      result of several neurodegenerative diseases. Herein, we investigated whether sub
      chronic intranasal administration of exogenous Hsp70 (eHsp70) exerts a
      neuroprotective effect on the temporal cortex and areas of the hippocampus in
      transgenic 5XFAD mice, a model of Alzheimer's disease. The quantitative analysis
      of neuronal pathologies in the compared groups, transgenic (Tg) versus non
      transgenic (nTg), revealed high level of abnormalities in the brains of
      transgenic mice. Treatment with human recombinant Hsp70 had profound rejuvenation
      effect on both neuronal morphology and functional state in the temporal cortex
      and hippocampal regions in transgenic mice. Hsp70 administration had a smaller,
      but still significant, effect on the functional state of neurons in non
      transgenic mice as well. Using deep sequencing, we identified multiple
      differentially expressed genes (DEGs) in the hippocampus of transgenic and non
      transgenic mice. Furthermore, this analysis demonstrated that eHsp70
      administration strongly modulates the spectrum of DEGs in transgenic animals,
      reverting to a pattern similar to that observed in non-transgenic age-matched
      mice, which included upregulation of genes responsible for amine transport,
      transmission of nerve impulses and other pathways that are impaired in 5XFAD
      mice. Overall, our data indicate that Hsp70 treatment may be an effective
      therapeutic against old age diseases of the Alzheimer's type.

PMID- 28759973
TI  - Reduced Empathy Scores in Patients with Parkinson's Disease: A Non-Motor Symptom
      Associated with Advanced Disease Stages.
AB  - BACKGROUND: Empathy describes the ability to infer and share emotional
      experiences of other people and is a central component of normal social
      functioning. Impaired empathy might be a non-motor symptom in Parkinson's disease
      (PD). OBJECTIVE: To examine empathic abilities and their relationship to clinical
      and cognitive functioning in PD patients. METHODS: Empathy was measured in 75 non
      demented PD patients and 34 age-matched healthy controls using a German version
      of the Interpersonal Reactivity Index. Moreover, we collected demographic and
      clinical data and conducted a comprehensive neuropsychological test battery.
      RESULTS: PD patients had a significant lower global empathy score than healthy
      controls. Furthermore, we found significant group differences for the cognitive
      empathy scales but not for the scales which are sensitive for affective empathy
      components. The empathy decrease was significantly higher in advanced Hoehn &
      Yahr stages. There were only sporadic significant correlations between empathy
      scores and cognitive variables. CONCLUSIONS: PD patients show a stage dependent
      empathy score decrease which is driven mainly by cognitive aspects of empathy.
      However, emotional empathy aspects are not reduced.

PMID- 28759968
TI  - A Systematic Review of Longitudinal Studies Which Measure Alzheimer's Disease
      Biomarkers.
AB  - Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease,
      with no effective treatment or cure. A gold standard therapy would be treatment
      to slow or halt disease progression; however, knowledge of causation in the early
      stages of AD is very limited. In order to determine effective endpoints for
      possible therapies, a number of quantitative surrogate markers of disease
      progression have been suggested, including biochemical and imaging biomarkers.
      The dynamics of these various surrogate markers over time, particularly in
      relation to disease development, are, however, not well characterized. We
      reviewed the literature for studies that measured cerebrospinal fluid or plasma
      amyloid-beta and tau, or took magnetic resonance image or
      fluorodeoxyglucose/Pittsburgh compound B-positron electron tomography scans, in
      longitudinal cohort studies. We summarized the properties of the major cohort
      studies in various countries, commonly used diagnosis methods and study designs.
      We have concluded that additional studies with repeat measures over time in a
      representative population cohort are needed to address the gap in knowledge of AD
      progression. Based on our analysis, we suggest directions in which research could
      move in order to advance our understanding of this complex disease, including
      repeat biomarker measurements, standardization and increased sample sizes.

PMID- 28759974
TI  - Correlations Between Methionine Cycle Metabolism, COMT Genotype, and
      Polyneuropathy in L-Dopa Treated Parkinson's Disease: A Preliminary Cross
      Sectional Study.
AB  - BACKGROUND: Polyneuropathy (pnp) is recognized as a clinical feature of
      Parkinson's disease (PD). Whether pnp is a result of the alpha-synucleinopathy or
      related to treatment is debated. Previous studies support underlying disturbances
      in the methionine cycle mediated by L-dopa. OBJECTIVE: Describe possible
      relationships between methionine cycle metabolism and the development of pnp in L
      dopa treated PD. Furthermore, we aim to investigate possible genetic risk factors
      by genotyping specific SNPs in enzymes involved in the abovementioned pathways.
      METHODS: In a cross-sectional study design, L-dopa treated PD patients (n = 33)
      and controls (n = 16) were evaluated with biochemical and genetic analyses.
      Subjects were assessed clinically and with regards to signs of pnp using
      established clinical neuropathy rating scales. RESULTS: 16/33 patients fulfilled
      a study diagnosis of pnp compared to 0 age-matched controls. Levels of
      homocysteine (Hcy) were significantly higher in patients with pnp (n = 16)
      compared to controls. A significant correlation between neuropathy scores and Hcy
      was seen in the whole patient group (n = 33). A significant difference in the
      genotype distribution of the COMT A158G polymorphism was demonstrated, favoring
      the low activity genotype in patients with pnp compared to both controls and
      patients without pnp. CONCLUSIONS: Pnp is a prevalent condition in L-dopa treated
      PD and an association may exist with elevated levels of Hcy, possibly reflecting
      an underlying impaired cellular methylation capacity. Furthermore, an association
      may exist between the low activity COMT genotype and pnp. These preliminary
      findings and the suggested pathophysiological mechanisms should be confirmed in
      future large-scale studies.

PMID- 28759975
TI  - Gastrointestinal Transit Time in Parkinson's Disease Using a Magnetic Tracking
      System.
AB  - BACKGROUND: Symptoms from the gastrointestinal tract are highly prevalent in
      Parkinson's disease (PD), but knowledge of the underlying pathology is incomplete
      and valid objective markers on regional gastrointestinal function are limited.
      OBJECTIVE: The aims were to evaluate gastrointestinal transit time and motility
      in PD patients and controls. METHODS: Twenty-two PD patients and 15 controls were
      included. Gastric-, small intestinal-, and caecum-ascending colonic transit times
      as well as colonic motility, defined as mass- and fast movements, were performed
      using the ambulatory 3D-Transit system. Gastrointestinal transit time with radio
      opaque markers, gastric emptying scintigraphy, and subjective non-motor symptoms
      were also evaluated. RESULTS: Using the 3D-Transit system, the patient group
      displayed significantly longer small intestinal- and caecum-ascending transit
      times (p = 0.030 and p = 0.0063). No between-group difference was seen in gastric
      transit time (p = 0.91). Time to first mass- and fast colonic movement were
      significantly increased in PD (p = 0.023 and p = 0.006). Radio opaque marker
      gastrointestinal transit time was significantly increased in the patient group (p
      < 0.0001), whereas no difference was seen in scintigraphic gastric emptying time
      (p = 0.68). Prevalence of constipation symptoms on the NMSQuest was 41% in PD and
      7% in controls. CONCLUSIONS: Significantly increased small intestinal- and caecum
      ascending 3D-Transit times were detected in PD patients. Also, time to first
      propagating colonic movement was increased. Radio opaque marker gastrointestinal
      transit time was significantly delayed, but no difference was seen in gastric
      transit time and gastric emptying time. The present findings highlight widespread
      intestinal involvement in PD increasing throughout the gastrointestinal tract.

PMID- 28759976
TI  - Correcting pelvic obliquity in the lateral position to improve acetabular
      component orientation during total hip arthroplasty.
AB  - BACKGROUND: The acetabular component orientation during total hip arthroplasty
      (THA) impacts future hip function and early revision. Correcting pelvic obliquity
      may improve outcomes. OBJECTIVE: To correct pelvic obliquity in the lateral
      position by applying a gradienter and plumb during THA using fluoroscopy.
      METHODS: Fifty patients undergoing THA were randomized and divided into 2 groups.
      In controls, acetabular components were placed using traditional methods. In
      experimental patients, acetabular components were placed after correcting pelvic
      obliquity. We measured pelvic obliquity and recorded intra-operative and post
      operative abduction angles, comparing abduction angle bias between post-operative
      measurements and intra-operation estimations. RESULTS: Before correction, the
      average pelvic obliquity was -1.647?+/- 4.512? in experimental patients. The
      average abduction angle in experimental patients was 42.685?+/- 3.355?
      postoperatively, differing by 1.962?+/- 1.515? from intra-operative estimates,
      while in control patients, it was 44.534?+/- 4.844? postoperatively, differing by
      4.244?+/- 3.042? from intra-operative estimates. The bias of the abduction angle
      was much greater in control than in experimental patients (P< 0.05). CONCLUSION:
      The pelvic obliquity in the lateral position affects surgeon judgment during THA.
      By correcting pelvic obliquity with a gradienter and plumb, the abduction angle
      bias can be reduced.

PMID- 28759977
TI  - Effects of progressive backward body weight suppoted treadmill training on gait
      ability in chronic stroke patients: A randomized controlled trial.
AB  - BACKGROUND AND OBJETIVE: A stroke patient with hemiplegic gait is generally
      described as being slow and asymmetric. Body weight-supported treadmill training
      and backward gait training are recent additions to therapeutic gait trainings
      that may help improve gait in stroke patient with hemiplegic gait. Therefore, we
      examined the effect of progressive backward body weight-supported treadmill
      training on gait in chronic stroke patients with hemiplegic gait. METHODS: Thirty
      subjects were divided to the experimental and control groups. The experimental
      group consisted of 15 patients and underwent progressive backward body weight
      supported treadmill training. The control group consisted of 15 patients and
      underwent general treadmill gait training five times per week, for a total of
      four weeks. The OptoGait was used to analyze gait kinematics, and the dynamic
      gait index (DGI) and results of the 6-minute walk test were used as the clinical
      evaluation indicators. A follow-up test was carried out four weeks later to
      examine persistence of exercise effects. RESULTS: The experimental group showed
      statistically significant results in all dependent variables week four compared
      to the control group. However, until the eighth week, only the dependent
      variables, of affected step length (ASL), stride length (SL), and DGI differed
      significantly between the two groups. CONCLUSION: This study verified that
      progressive bodyweight-supported treadmill training had a positive influence on
      the temporospatial characteristics of gait and clinical gait evaluation index in
      chronic stroke patients.

PMID- 28759978
TI  - A novel PLIF PEEK interbody cage with an impactionless insertion technology: A
      case series with a mid-term follow up of three years.
AB  - BACKGROUND: Spinal fusion surgery has become one of the most common spinal
      procedures during the recent years. Searching for an optimum structural stability
      of the vertebral interspace, surgical implants which can be inserted via a
      posterior lumbar interbody fusion (PLIF) approach have been enhanced recently.
      OBJECTIVE: Evaluation of safety and efficacy of a novel PLIF polyetheretherketone
      (PEEK) interbody cage (TWIST) with an impactionless insertion technique. METHODS:
      Surgical outcome in 15 patients treated with the new system were observed
      preoperatively, one and three years after surgery using the Oswestry Disability
      Index (ODI), a Visual Analogue Scale (VAS) for pain and radiological outcome
      analysis of fusion success. RESULTS: Fifteen patients (7 female, 8 male) were
      included in the test series. After three years ODI and VAS were significantly
      improved. The pain intensity was reduced by more than 75% after one year and
      after 3 years, pain intensity was about 60% below the initial situation. The
      Oswestry values (ODI) improved significantly in all patients after 3 years. The
      fusion evaluation showed a fusion success in 87% of the patients. CONCLUSION: The
      clinical and radiological results of this first series give a positive standing
      and important information on the efficacy and safety over 3 years. The follow-up
      checks with imaging techniques showed that the fusions were very successful and
      functional outcome as well as pain reduction were increased.

PMID- 28759979
TI  - Reconstruction of acetabular posterior wall fractures with extension to the roof
      using dual arc-shaped plates: A case report.
AB  - Anatomical reduction and rigid fixation of acetabular posterior wall fractures
      extending to the acetabular roof proves challenging because of the big bony
      fragment and muscular obstruction to accessing this region. This report describes
      a novel reconstructive technique in a patient with an acetabular posterior wall
      fracture involving the acetabular roof. Both the standard Kocher-Langenbeck
      approach and a greater trochanter osteotomy technique were used. Following
      anatomical reduction, a dual arc-shaped reconstruction plate technique was
      employed to achieve rigid fixation. The patient recovered with satisfactory
      function at the injured hip. We recommend this dual arc-shaped reconstruction
      plate technique for the treatment of acetabular posterior wall fractures
      extending to the acetabular roof in clinical practice.

PMID- 28759980
TI  - Evaluating the features of the brain waves to quantify ADHD improvement by
      neurofeedback.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD), as one of the most
      common neurological disorders in children and adolescents, is characterized by
      decentralization, slow learning, distraction and hyperactivity. Studies have
      shown that in addition to medication, neurofeedback training can also be used to
      partially control the brain activity of these patients. METHODS: In this study,
      using the brain signals processing before and after the treatment in 10 children
      treated by neurofeedback, the changes were evaluated by non-parametric
      statistical analysis and impact of neurofeedback on brain frequency bands was
      investigated. Finally, the results were compared with the protocols introduced in
      this paper and before researches. RESULTS: The results of Kruskal-Wallis test
      showed an approximately significant increase in the relative power of gamma and
      an approximately significant reduction in the ratio of relative power of
      alpha/beta. CONCLUSIONS: It represents the emotional response, elicited by the
      successful learning and diminished ratio of slow learning to active learning
      respectively.

PMID- 28759981
TI  - A numerical model for blast injury of human thorax based on digitized visible
      human.
AB  - Knowledge of the pressure distribution around human thorax in blast help to
      understand the injury mechanisms and their assessment. To investigate the
      transmission mechanism of the pressure on human thorax in blast, a three
      dimension surface model of human thorax was constructed in this work. To increase
      the precious of this model, tetrahedron element division method was applied to
      transfer the rough 3D surface model to hexahedral elements model. Using this
      model, the high pressure duration was computationally solved using numerical
      simulation of the hexahedral elements. Simulation results showed that the apex of
      lungs was subjected to the largest stress in a blast. In order to verify this
      result, an animal experiment was performed on a dog. The animal experimental
      results was shown to have a same variation tendency with the calculation results
      based on our numerical model of human thorax, which made this model reliable for
      the blast injury research.

PMID- 28759982
TI  - The validity and reliability of a dynamic neuromuscular stabilization-heel
      sliding test for core stability.
AB  - BACKGROUND: Core stabilization plays an important role in the regulation of
      postural stability. To overcome shortcomings associated with pain and severe core
      instability during conventional core stabilization tests, we recently developed
      the dynamic neuromuscular stabilization-based heel sliding (DNS-HS) test.
      OBJECTIVE: The purpose of this study was to establish the criterion validity and
      test-retest reliability of the novel DNS-HS test. METHOD: Twenty young adults
      with core instability completed both the bilateral straight leg lowering test
      (BSLLT) and DNS-HS test for the criterion validity study and repeated the DNS-HS
      test for the test-retest reliability study. Criterion validity was determined by
      comparing hip joint angle data that were obtained from BSLLT and DNS-HS measures.
      The test-retest reliability was determined by comparing hip joint angle data.
      RESULTS: Criterion validity was (ICC2,3) = 0.700 (p< 0.05), suggesting a good
      relationship between the two core stability measures. Test-retest reliability was
      (ICC3,3) = 0.953 (p< 0.05), indicating excellent consistency between the repeated
      DNS-HS measurements. CONCLUSIONS: Criterion validity data demonstrated a good
      relationship between the gold standard BSLLT and DNS-HS core stability measures.
      Test-retest reliability data suggests that DNS-HS core stability was a reliable
      test for core stability. Clinically, the DNS-HS test is useful to objectively
      quantify core instability and allow early detection and evaluation.

PMID- 28759983
TI  - Validation of CT image-based software for three-dimensional measurement of
      acetabular coverage profile.
AB  - BACKGROUND: Plain radiography, 2-dimensional (2D) magnetic resonance imaging
      (MRI), and computed tomography (CT) do not precisely display morphology and
      acetabular coverage in developmental dysplasia of the hip or pincer-type
      femoroacetabular impingement. Pelvic position and pelvic tilt affect assessment
      of the acetabular parameters, leading to misinterpretation. OBJECTIVE: We tested
      a 3-dimensional (3D) CT evaluation script to calculate the crossover sign (COS),
      acetabular coverage and morphology. METHODS: To test the method, we constructed a
      phantom pelvic model, in which the acetabulum was mounted at different coverages
      of the femoral head, and simulated a COS and the acetabular morphology.
      Additionally we examined the reliability and objectivity of this method in ten
      patients with CT scans of the pelvis for conditions unrelated to hip disorders.
      RESULTS: We obtained an average accuracy of the 3D CT evaluation script of -0.37?
      (range -3.84 to 3.88; SD +/- 1.43) for morphology, and 0.002% (range -7.28% to
      6.90%; SD +/- 1.60%) for coverage of the femoral head. Significant correlation
      between the expected and calculated COS (p= 0.01) was found. CONCLUSIONS: Our 3D
      CT evaluation script permits precise evaluation of the acetabular coverage
      profile, the presence or absence of a COS and acetabular morphology, independent
      of patient positioning or pelvic tilt.

PMID- 28759984
TI  - RFID of next generation network for enhancing customer relationship management in
      healthcare industries.
AB  - This paper aims to analyze possible next generation of networked radio frequency
      identification (NGN-RFID) system for customer relationship management (CRM) in
      healthcare industries. Customer relationship and its management techniques in a
      specific healthcare industry are considered in this development. The key
      objective of using NGN-RFID scheme is to enhance the handling of patients' data
      to improve the CRM efficiency in healthcare industries. The proposed NGN-RFID
      system is one of the valid points to improve the ability of CRM by analyzing
      different prior and current traditional approaches. The legacy of customer
      relationship management will be improved by using this modern NGN-RFID technology
      without affecting the novelty.

PMID- 28759986
TI  - Electrical Properties of Composite Materials with Electric Field-Assisted
      Alignment of Nanocarbon Fillers.
AB  - The article reports about electric field-induced alignment of the carbon
      nanoparticles embedded in epoxy matrix. Optical microscopy was performed to
      consider the effect of the electric field magnitude and configuration, filler
      morphology, and aspect ratio on alignment process. Characteristic time of aligned
      network formation was compared with modeling predictions. Carbon nanotube and
      graphite nanoplatelet rotation time was estimated using an analytical model based
      on effective medium approach. Different depolarization factor was applied
      according to the geometries of the particle and electric field.Solid
      nanocomposites were fabricated by using AC electric field. We have investigated
      concentration dependence of electrical conductivity of graphite
      nanoplatelets/epoxy composites using two-probe technique. It was established that
      the electrical properties of composites with random and aligned filler
      distribution are differ by conductivity value at certain filler content and
      distinguish by a form of concentration dependence of conductivity for fillers
      with different morphology. These differences were explained in terms of the
      dynamic percolation and formation of various conductive networks: chained in case
      of graphite nanoplatelets and crossed framework in case of carbon nanotubes
      filler.

PMID- 28759987
TI  - Theoretical Investigation of Biaxially Tensile-Strained Germanium Nanowires.
AB  - We theoretically investigate highly tensile-strained Ge nanowires laterally on
      GaSb. Finite element method has been used to simulate the residual elastic strain
      in the Ge nanowire. The total energy increment including strain energy, surface
      energy, and edge energy before and after Ge deposition is calculated in different
      situations. The result indicates that the Ge nanowire on GaSb is apt to grow
      along <100> rather than <110> in the two situations and prefers to be exposed by
      {105} facets when deposited a small amount of Ge but to be exposed by {110} when
      the amount of Ge exceeds a critical value. Furthermore, the conduction band
      minima in Gamma-valley at any position in both situations exhibits lower values
      than those in L-valley, leading to direct bandgap transition in Ge nanowire. For
      the valence band, the light hole band maxima at Gamma-point is higher than the
      heavy hole band maxima at any position and even higher than the conduction band
      minima for the hydrostatic strain more than ~5.0%, leading to a negative bandgap.
      In addition, both electron and hole mobility can be enhanced by owing to the
      decrease of the effective mass under highly tensile strain. The results suggest
      that biaxially tensile-strained Ge nanowires hold promising properties in device
      applications.

PMID- 28759988
TI  - Comparative analysis of stirred catalytic basket bio-reactor for the production
      of bio-ethanol using free and immobilized Saccharomyces cerevisiae cells.
AB  - The successful industrial production of ethanol and fine chemicals requires the
      development of new biocatalytic reactors and support materials to achieve
      economically viable processes. In this work, a Stirred-Catalytic-Basket
      BioReactor using various immobilizing foams as support material and compared to
      free cells were used, focusing mainly on; (i) effect of mass-transfer on cells
      physiology and (ii) ethanol productivity. The performance of the reactor was
      further evaluated by ethanol volumetric productivity, yield and time for process
      completion and it was found that the variation of ethanol production and
      diffusion of the substrate in fermentation process are co-related with the
      stirrer speed and initial glucose concentration. It was also observed that the
      time difference for glucose consumption between free and immobilized cells
      (alginate and sponges) tends to increase by increasing the glucose concentration
      in the medium. We found that at higher stirrer speed (500 rpm) when using higher
      glucose concentration (200 g/l), ethanol volumetric productivity increased
      significantly in the sponge (85 g/l) as compared to alginate beads (79 g/l) and
      free cells (60 g/l). From the data obtained, it can be concluded that sponges are
      the best support material for attaining higher ethanol productivity. A stirred
      catalytic basket bioreactor with yeast cells immobilized in polyethylene sponge
      gives higher ethanol production at a higher glucose consumption rate, and this
      productivity is due to higher mixing efficiency and reduced external as well as
      internal mass transfer limitations. The potentials of the reactor rank it as a
      remarkable ethanol/fine-chemical production approach that needs further
      investigations.

PMID- 28759989
TI  - Resection plane-dependent error in computed tomography volumetry of the right
      hepatic lobe in living liver donors.
AB  - BACKGROUND/AIMS: Computed tomography (CT) hepatic volumetry is currently accepted
      as the most reliable method for preoperative estimation of graft weight in living
      donor liver transplantation (LDLT). However, several factors can cause
      inaccuracies in CT volumetry compared to real graft weight. The purpose of this
      study was to determine the frequency and degree of resection plane-dependent
      error in CT volumetry of the right hepatic lobe in LDLT. METHODS: Forty-six
      living liver donors underwent CT before donor surgery and on postoperative day 7.
      Prospective CT volumetry (VP) was measured via the assumptive hepatectomy plane.
      Retrospective liver volume (VR) was measured using the actual plane by comparing
      preoperative and postoperative CT. Compared with intraoperatively measured weight
      (W), errors in percentage (%) VP and VR were evaluated. Plane-dependent error in
      VP was defined as the absolute difference between VP and VR. % plane-dependent
      error was defined as follows: |VP-VR|/W?100. RESULTS: Mean VP, VR, and W were
      761.9 mL, 755.0 mL, and 696.9 g. Mean and % errors in VP were 73.3 mL and 10.7%.
      Mean error and % error in VR were 64.4 mL and 9.3%. Mean plane-dependent error in
      VP was 32.4 mL. Mean % plane-dependent error was 4.7%. Plane-dependent error in
      VP exceeded 10% of W in approximately 10% of the subjects in our study.
      CONCLUSIONS: There was approximately 5% plane-dependent error in liver VP on CT
      volumetry. Plane-dependent error in VP exceeded 10% of W in approximately 10% of
      LDLT donors in our study. This error should be considered, especially when CT
      volumetry is performed by a less experienced operator who is not well acquainted
      with the donor hepatectomy plane.

PMID- 28759990
TI  - Risk Factors for a False-Negative Result of Sentinel Node Biopsy in Patients with
      Clinically Node-Negative Breast Cancer.
AB  - Purpose: Although sentinel lymph node biopsy (SLNB) can accurately represent the
      axillary lymph node (ALN) status, the false-negative rate (FNR) of SLNB is the
      main concern in the patients who receive SLNB alone instead of ALN dissection
      (ALND). Materials and Methods: We analyzed 1,886 patientswho underwent ALND after
      negative results of SLNB,retrospectively. A logistic regression analysis was used
      to identify risk factors associated with a falsenegative (FN) result. Cox
      regression model was used to estimate the hazard ratio of factors affecting
      disease-free survival (DFS). Results: Tumor located in the upper outer portion of
      the breast, lymphovascular invasion, suspicious node in imaging assessment and
      less than three sentinel lymph nodes (SLNs) were significant independent risk
      factors for FN in SLNB conferring an adjusted odds ratio of 2.10 (95% confidence
      interval [CI], 1.30 to 3.39), 2.69 (95% CI, 1.47 to 4.91), 2.59 (95% CI, 1.62 to
      4.14), and 2.39 (95% CI, 1.45 to 3.95), respectively. The prognostic factors
      affecting DFS were tumor size larger than 2 cm (hazard ratio [HR], 1.86; 95% CI,
      1.17 to 2.96) and FN of SLNB (HR, 2.51; 95% CI, 1.42 to 4.42) in SLN-negative
      group (FN and true-negative), but in ALN-positive group (FN and true-positive),
      FN of SLNB (HR, 0.64; 95% CI, 0.33 to 1.25) did not affect DFS. Conclusion: In
      patients with risk factors for a FN such as suspicious node in imaging
      assessment, upper outer breast cancer, less than three harvested nodes, we need
      attention to find another metastatic focus in non-SLNs during the operation. It
      may contribute to provide an exact prognosis and optimizing adjuvant treatments.

PMID- 28759991
TI  - In Silico Prediction of Ligand Binding Energies in Multiple Therapeutic Targets
      and Diverse Ligand Sets-A Case Study on BACE1, TYK2, HSP90, and PERK Proteins.
AB  - We present here the use of QM/MM LIE (linear interaction energy) based binding
      free energy calculations that greatly improve the precision and accuracy of
      predicting experimental binding affinities, in comparison to most current binding
      free energy methodologies, while maintaining reasonable computational times.
      Calculations are done for four sets of ligand-protein complexes, chosen on the
      basis of diversity of protein types and availability of experimental data,
      totaling 140 ligands binding to therapeutic protein targets BACE1, TYK2, HSP90,
      and PERK. This method allows calculations for a diverse set of ligands and
      multiple protein targets without the need for parametrization or extra
      calculations. The accuracy achieved with this method can be used to guide small
      molecule computational drug design programs.

PMID- 28759992
TI  - Tandem Synthesis of alpha-Diazoketones from 1,3-Diketones.
AB  - A highly efficient synthesis of alpha-diazoketone was achieved by simply stirring
      the mixture of 1,3-diketone, TsN3, and MeNH2 in EtOH. It was a tandem reaction
      including a novel primary amine-catalyzed Regitz diazo transfer of 1,3-diketone
      and a novel primary amine-mediated C-C bond cleavage of 2-diazo-1,3-diketone.

PMID- 28759993
TI  - CuCl-Catalyzed Hydroxylation of N-Heteroarylcarbazole Bromide: Approach for the
      Preparation of N-Heteroarylcarbazolyl Phenols and Its Application in the
      Synthesis of Phosphorescent Emitters.
AB  - An efficient and practical CuCl-catalyzed hydroxylation of N-heteroarylcarbazole
      bromide for the preparation of N-heteroarylcarbazolyl phenols with a broad
      functional group scope and yield up to 98% was developed. It was found that both
      the ligand and base played critical roles in the functional group transformation
      and that different products could be generated by changing the base for some
      substrates. t-BuONa was demonstrated to be a better base for the catalytic system
      to avoid the formation of the ether byproduct. In addition, this approach was
      suitable for large-scale preparation and was successfully applied in the gram
      scale synthesis of phosphorescent emitters PtNON and PdNON, demonstrating its
      practicability in organic synthesis methodology and materials science.
      Furthermore, the X-ray crystal diffraction, DFT calculations, and photophysical
      properties were also investigated for the metal complexes.

PMID- 28759994
TI  - Trimodal Mixed Mode Chromatography That Enables Efficient Offline Two-Dimensional
      Peptide Fractionation for Proteome Analysis.
AB  - Offline two-dimensional chromatography is a common means to achieve deep proteome
      coverage. To reduce sample complexity and dynamic range and to utilize mass
      spectrometer (MS) time efficiently, high chromatographic resolution of and good
      orthogonality between the two dimensions are needed. Ion exchange and high pH
      reversed phase chromatography are often used for this purpose. However, the
      former requires desalting to be MS-compatible, and the latter requires fraction
      pooling to create orthogonality. Here, we report an alternative first-dimension
      separation technique using a commercial trimodal phase incorporating polar
      embedded reversed phase, weak anion exchange, and strong cation exchange
      material. The column is capable of retaining polar and nonpolar peptides alike
      without noticeable breakthrough. It allows separating ordinary and TMT-labeled
      peptides under mild acidic conditions using an acetonitrile gradient. The direct
      MS compatibility of solvents and good orthogonality to online coupled C18 columns
      enable a straightforward workflow without fraction pooling and desalting while
      showing comparable performance to the other techniques. The method scales from
      low to high microgram sample quantity and is amenable to full automation. To
      demonstrate practical utility, we analyzed the proteomes of 10 human pancreatic
      cancer cell lines to a depth of >8,700 quantified proteins.

PMID- 28759995
TI  - Multilayer Choline Phosphate Molecule Modified Surface with Enhanced Cell
      Adhesion but Resistance to Protein Adsorption.
AB  - Choline phosphate (CP), which is a new zwitterionic molecule, and has the reverse
      order of phosphate choline (PC) and could bind to the cell membrane though the
      unique CP-PC interaction. Here we modified a glass surface with multilayer CP
      molecules using surface-initiated atom-transfer radical polymerization (SI-ATRP)
      and the ring-opening method. Polymeric brushes of (dimethylamino)ethyl
      methacrylate (DMAEMA) were synthesized by SI-ATRP from the glass surface. Then
      the grafted PDMAEMA brushes were used to introduce CP groups to fabricate the
      multilayer CP molecule modified surface. The protein adsorption experiment and
      cell culture test were used to evaluate the biocompatibility of the modified
      surfaces by using human umbilical veinendothelial cells (HUVECs). The protein
      adsorption results demonstrated that the multilayer CP molecule decorated surface
      could prevent the adsorption of fibrinogen and serum protein. The adhesion and
      proliferation of cells were improved significantly on the multilayer CP molecule
      modified surface. Therefore, the biocompatibility of the material surface could
      be improved by the modified multilayer CP molecule, which exhibits great
      potential for biomedical applications, e.g., scaffolds in tissue engineering.

PMID- 28759996
TI  - Real-Time Elucidation of Catalytic Pathways in CO Hydrogenation on Ru.
AB  - The direct elucidation of the reaction pathways in heterogeneous catalysis has
      been challenging due to the short-lived nature of reaction intermediates. Here,
      we directly measured on ultrafast time scales the initial hydrogenation steps of
      adsorbed CO on a Ru catalyst surface, which is known as the bottleneck reaction
      in syngas and CO2 reforming processes. We initiated the hydrogenation of CO with
      an ultrafast laser temperature jump and probed transient changes in the
      electronic structure using real-time X-ray spectroscopy. In combination with
      theoretical simulations, we verified the formation of CHO during CO
      hydrogenation.

PMID- 28759997
TI  - Turn-on Fluorescent Probe for Exogenous and Endogenous Imaging of Hypochlorous
      Acid in Living Cells and Quantitative Application in Flow Cytometry.
AB  - Hypochlorous acid (HClO) acts as a dominant microbicidal mediator in the natural
      immune system, and the excess production of hypochlorites is related to a series
      of diseases. Thus, it is vitally important and necessary to develop a highly
      sensitive and selective method for HClO detection in living systems, and most of
      fluorescent probes are mainly focused on cells imaging. Besides, accurate HClO
      quantitative information about individual cells in a large cell population is
      extremely important for understanding inflammation and cellular apoptosis as
      well. In our work, a turn-on fluorescent probe has been synthesized, which can
      selectively and sensitively detect HClO with fast response time. The probe is
      almost nonfluorescent possibly due to both the spirolactam form of fluorescein
      and unbridged C?N bonds which can undergo a nonradiative decay process in the
      excited state. Upon the addition of ClO-, the probe was oxidized to ring-opened
      fluorescent form and the fluorescence intensity was greatly enhanced. In live
      cell experiments, the probe was successfully applied to image exogenous ClO- in
      HeLa cells and endogenous HClO in RAW 264.7 macrophage cells. In particular, the
      quantitative information on exogenous and endogenous HClO can also be acquired in
      flow cytometry. Therefore, the probe not only can image exogenous and endogenous
      HClO but also provides a new and promising platform to quantitatively detect HClO
      in flow cytometry.

PMID- 28759998
TI  - Pharmacist Participation in Acute Ischemic Stroke Decreases Door-to-Needle Time
      to Recombinant Tissue Plasminogen Activator.
AB  - BACKGROUND: Pharmacists are an important member of the stroke team and aid in
      obtaining medication and medical history, providing education, managing blood
      pressure, reviewing exclusion criteria for recombinant tissue plasminogen
      activator (rtPA), and facilitating reconstitution and administration of rtPA.
      OBJECTIVE: To determine if pharmacist presence at bedside during acute ischemic
      stroke resulted in a reduction in door-to-needle (DTN) times. METHODS: This was a
      retrospective cohort study between January 1, 2011 and December 31, 2015 of
      patients who received rtPA for acute ischemic stroke in either the emergency
      department or hospital. RESULTS: Of the 125 included patients, 45 patients (36%)
      had a pharmacist present (PharmD group) and 80 patients (64%) did not (no PharmD
      group). Median DTN time was significantly shorter in the PharmD group: 48 minutes
      versus 73 minutes in the no PharmD group ( P < 0.01). The goal of DTN <=60
      minutes was met in 71% of patients in the PharmD group compared to 29% ( P <
      0.01). Pharmacist at the bedside was the only factor found to be independently
      associated with reduction DTN time (betacoefficient -23.5 minutes, 95% confidence
      interval [95% CI] -38.6 to -8.50 minutes). CONCLUSION: A pharmacist at the
      bedside of emergency department or in-patient stroke codes reduced DTN time by a
      median of 23.5 minutes after adjusting for confounding factors and increased the
      percentage of patients meeting DTN goal time of <=60 minutes by 49%. These
      findings support the inclusion of a stroke-competent pharmacist in the bedside
      response team for acute ischemic stroke patients.

PMID- 28759999
TI  - Effect of a National Tobacco Public Education Campaign on Youth's Risk
      Perceptions and Beliefs About Smoking.
AB  - PURPOSE: To assess the relationship between youth's exposure to the Food and Drug
      Administration's national tobacco public education campaign, The Real Cost, and
      changes in campaign-targeted beliefs. DESIGN: Longitudinal design with baseline
      survey and 2 postcampaign follow-up surveys. SAMPLE: Youth from 75 US media
      markets (N = 1680) who completed all 3 surveys and had experimented with or were
      susceptible to future cigarette smoking. MEASURES: Exposure was measured by self
      reported frequency of ad exposure and media market-level target rating points.
      Agreement with 30 self-reported tobacco-related beliefs was assessed in 3
      categories: (1) beliefs specifically targeted by campaign messages (campaign
      targeted belief), (2) beliefs not targeted by the campaign (nontargeted beliefs),
      and (3) beliefs corresponding to other media campaigns on air concurrent with The
      Real Cost (ambiguous beliefs). ANALYSIS: Descriptive analyses of aggregate
      changes in beliefs and logistic regressions to examine the association between
      campaign exposure and beliefs. INTERVENTION: The Real Cost. RESULTS: Agreement
      with campaign-targeted beliefs increased from baseline to first and second follow
      ups, with a mean relative increase of 10.4% and 11.5%, respectively. Nontargeted
      beliefs did not change substantially. Both measures of campaign exposure were
      positively associated with increased odds of agreeing with 5 of 8 campaign
      targeted beliefs. Exposure was not significantly associated with 12 of 14
      nontargeted tobacco-related beliefs. DISCUSSION: A sustained national tobacco
      public education campaign can change population-level perceptions of tobacco
      related harms among youth.

PMID- 28760000
TI  - Cholesterol derivative-based liposomes for gemcitabine delivery: preparation, in
      vitro, and in vivo characterization.
AB  - As an anti-tumor drug, gemcitabine (Gem) is commonly used for the treatment of
      non-small cell lung cancer and pancreatic cancer. However, there are several
      clinical drawbacks to using Gem, including its extremely short plasma half-life
      and side effects. To prolong its half-life and reduce its side effects, we
      synthesized a derivative of Gem using cholesterol (Chol). This derivative, called
      gemcitabine-cholesterol (Gem-Chol), was entrapped into liposomes by a thin-film
      dispersion method. The particle size of the Gem-Chol liposomes was 112.57 +/-
      1.25 nm, the encapsulation efficiency was above 99%, and the drug loading
      efficiency was about 50%. In vitro studies revealed that the Gem-Chol liposomes
      showed delayed drug release and long-term stability at 4  degrees C for up to 2
      months. In vivo studies also showed the superiority of the Gem-Chol liposomes,
      and compared with free Gem, the Gem-Chol liposomes had longer circulation time.
      Moreover, an anti-tumor study in H22 and S180 tumor models showed that liposomal
      entrapment of Gem-Chol improved the anti-tumor effect of Gem. This study reports
      a potential formulation of Gem for clinical application.

PMID- 28760001
TI  - Association of obesity with healthcare utilization and costs in a Medicare
      population.
AB  - OBJECTIVES: To examine the association of obesity with healthcare resource
      utilization and costs in a Medicare population. METHODS: This study was a
      retrospective cohort study using Humana Medicare Advantage (MA) claims data. Body
      mass index (BMI) was assessed using ICD-9-CM status codes (V85 hierarchy) that
      have been validated in the data source to classify patients into BMI categories:
      normal (N), overweight (Ow), obese class I (ObI), obese class II (ObII), and
      obese class III (ObIII). Healthcare resource utilization (HRU) and costs were
      determined based on claims data. Descriptive statistics were used to examine
      baseline characteristics and HRU across BMI classes. Multivariable analysis was
      used to examine the association between BMI class and outcome measures. RESULTS:
      Among the 172,866 patients aged >=65 years that were identified, BMI distribution
      was: N, 21%; Ow 37%; ObI, 24%, ObII, 10%; and ObIII, 9%. Inpatient, emergency
      department and outpatient utilization increased with greater BMI level, and
      greater BMI level was associated with higher total healthcare, medical and
      pharmacy costs. Greater prevalence of several cardiometabolic conditions, total
      medication use, and use of specific medication classes was observed with
      increasing BMI class. CONCLUSIONS: Greater BMI was associated with greater HRU
      and costs and observed increase in prevalence of cardiometabolic conditions.
      These results reflect an urgent need to address the epidemic of obesity and the
      resulting excessive clinical and economic burden on the healthcare system.

PMID- 28760002
TI  - Measuring racial microaggression in medical practice.
AB  - The purpose of this study was to validate the already existing Racial
      Microaggression in Counseling Scale (RMCS) when the term 'therapist' was replaced
      with 'physician', thus constituting the modification as the Racial
      Microaggression in Medical Practice Scale (RMMPS). Racial microaggressions work
      at reinforcing inferior social status on a cognitive level. Unlike overt racism,
      messages behind microaggression are subtler and more every day. A lack of
      acceptance, respect, and regard emerges from interactions in medical contexts as
      there are layers of in-group and out-group statuses at play (e.g. physician
      patient, Black-White, expert-lay, and Westernized-alternative). The layer focused
      on in this study was that of race or skin color. A sample of racial minorities in
      the Northeast (n = 91) was investigated both quantitatively and qualitatively to
      validate the modification and future use of a RMMPS. The scale was related to the
      racial incongruence between patient and provider. Qualitative findings support
      the original concepts and themes used when developing the 10-item measure in a
      counseling setting. Psychometric findings for the scale also supported its
      factorial structure using generalizability theory estimates. Future implications
      of this research relate to health behavior, trustworthiness, and health outcomes
      of minority patients. Its potential for use among various practitioners,
      educators, and researchers is also discussed.

PMID- 28760003
TI  - Surgical outcomes of laparoscopic endometriosis surgery: a 6 year experience.
AB  - OBJECTIVES: The aim of the present study was to review 6 year experience on the
      surgical outcomes of laparoscopic endometriosis surgery. METHODS: A cohort study
      was performed in Shiraz University of Medical Sciences using data from medical
      records of 1315 cases of patients with endometriosis undergoing laparoscopic
      surgery with follow-up of 6 to 72 months. RESULTS: This study concerned a cohort
      of 1315 patients diagnosed with endometriosis operated between April 2010 and
      April 2016, 1086 (82.5%) of whom were in stage III and IV; 968 (73.61%) had
      endometrioma (regardless of having deep infiltrative endometriosis [DIE] or
      peritoneal involvement) and 347 (26.39%) of patients had either DIE or peritoneal
      involvement without endometrioma. Regarding the patients, unilateral endometrioma
      was statistically significant in the left ovary (p = .002). One hundred and
      thirty-three (10.7%) rectal wall, 7 (0.32%) sigmoid colon, 4 (0.18%) vagina, 125
      (5.6%) ureter and 33 (1.52) bladder involvements were detected. Prior to
      operation, the pain VAS score was 8.23 +/- 2.03, which decreased to 4.46 +/- 2.47
      in 93.07% of patients. Fifty-three patients (6.56%) needed reoperation. Sixty-six
      (33.1%) infertile women had spontaneous pregnancy and 15 (25%) became pregnant
      using intrauterine insemination (IUI) or assisted reproductive technique (ART)
      post-operatively. CONCLUSION: Surgical treatment of endometriosis seems to be an
      effective treatment. DIE can be present in the absence of endometrioma. The rate
      of left endometrioma is higher due to the pressure effect of the sigmoid colon.
      Nonetheless, if an expert surgeon performs this procedure, not only the rate of
      post-operative complications, but also the possibility of recurrence would
      decrease.

PMID- 28760004
TI  - Hepatocellular carcinoma with central scar on gadoxetic acid-enhanced and
      diffusion-weighted magnetic resonance imaging.
AB  - Background Central scars are rarely reported in conventional hepatocellular
      carcinoma (HCC). The presence of central scars on imaging might lead to erroneous
      diagnosis of hepatic tumors. Purpose To determine imaging features of HCC with
      central scars on magnetic resonance imaging (MRI) including gadoxetic acid
      enhanced and diffusion-weighted imaging (DWI). Material and Methods Fifty-one
      patients with 51 surgically confirmed HCCs with central scars (fibrotic scar: n =
      50; myxoid scar: n = 1; range = 1.2-15 cm; mean = 3.7 cm) underwent liver MRI
      that consisted of T1- and T2-weighted (T2W) imaging, gadoxetic acid-enhanced
      arterial, portal, 3-min late phase, and 20-min hepatobiliary phase (HBP), and
      DWI. Two reviewers evaluated morphology, signal intensity, and enhancement
      features of tumors and central scars for each image and reached consensus.
      Results Lobulated contour was seen for 30 tumors (58.8%); the rest were round or
      oval masses. Central scars (range = 0.2-6.0 cm; mean = 0.9 cm) were most commonly
      seen as defects within hyperenhancement on arterial phase images (n = 47, 92.2%),
      bright (n = 28, 54.9%) or dark areas (n = 15, 29.4%) on T2W imaging, areas of
      central darkness on high b-value DWI (b = 800) (n = 31, 60.8%), and/or central
      enhancement on HBP (n = 36, 70.6%), mimicking a target appearance. Tumor capsule
      was seen in 35 (39 pathology, 74.5%) and intratumoral septum in 35 (41 pathology,
      78.4%) tumors on gadoxetic acid-enhanced MRI. Conclusion Non-fibrolamellar HCC
      may show central scar. HCC with central scar mimics cholangiocarcinoma by showing
      a target appearance on HBP and DWI. Tumor capsule and intratumoral septum might
      be useful for characterizing HCC with central scar.

PMID- 28760005
TI  - Evidence based selection of probiotic strains to promote astronaut health or
      alleviate symptoms of illness on long duration spaceflight missions.
AB  - Spaceflight impacts multiple aspects of human physiology, which will require non
      invasive countermeasures as mission length and distance from Earth increases and
      the capability for external medical intervention decreases. Studies on Earth have
      shown that probiotics have the potential to improve some of the conditions that
      have manifested during spaceflight, such as gastrointestinal distress,
      dermatitis, and respiratory infections. The constraints and risks of spaceflight
      make it imperative that probiotics are carefully selected based on their strain
      specific benefits, doses, delivery mechanisms, and relevance to likely crew
      conditions prior to evaluation in astronauts. This review focuses on probiotics
      that have been incorporated into healthy human gastrointestinal microbiomes and
      associated clinically with improvements in inflammatory state or alleviation of
      symptoms of crew-relevant illness. These studies provide an evidence base for
      probiotic selection with the greatest potential to support crew health and well
      being in spaceflight.

PMID- 28760006
TI  - Biological activity and LC-MS profiling of ethyl acetate extracts from Nitraria
      sibirica (Pall.) fruits.
AB  - Nitraria sibirica is a traditional Uighur medicine. This study was undertaken to
      investigate the bioactivity of N. sibirica fruit extract and to evaluate their
      chemical compositions. The ethyl acetate extract from N. sibirica fruits
      exhibited the potential antioxidant activity (SC50 = 30.17 +/- 0.06 MUg/mL) and
      protein tyrosine phosphatase 1B inhibitory activity (IC50 = 7.15 +/- 0.03 MUg/mL)
      in vitro. In order to investigate the active constituents in this extract, a LC
      QTOF-MS/MS method was developed and established. A total of 28 compounds
      including seven cinnamic acids, nine benzoic acids and 12 flavonoids were
      identified or partially characterised according to the accurate mass and the
      characteristic fragment ions at low and high collision energy. Most of them were
      reported for the first time in this plant. Phytochemical profiles of the active
      extract will help the development and utilisation of N. sibirica in food and
      medicine.

PMID- 28760007
TI  - Double Fortified Salt Intervention Improved Iron Intake But Not Energy and Other
      Nutrient Intakes in Female Tea Plantation Workers From West Bengal, India.
AB  - BACKGROUND: Iron deficiency is a global public health concern and has
      implications on the health status of women in reproductive age. OBJECTIVE: We
      hypothesized that improving iron intake with double fortified salt would improve
      food intake, resulting in higher energy, nutrient intakes, and weight indicators
      of female tea plantation workers. METHODS: In this randomized double-masked
      study, the participants (n = 245) were assigned to receive salt double fortified
      with iron and iodine (DFS; treatment) or salt fortified with iodine (control) and
      followed for 7.5 to 9 months. Dietary intakes were measured at three time points,
      baseline, midpoint, and end line using (1) food frequency questionnaire, (2) 24
      hour recall, and (3) weighed lunch intake. Anthropometric measures of height
      (cm), weight (kg), and mid-upper arm circumference (cm) were also recorded at
      three time points. Mixed-model repeated-measures approach was used to detect
      group differences across time. RESULTS: Double fortified salt improved dietary
      iron intake in the treatment group compared to the control group ( P < .001). No
      other dietary or anthropometric differences could be attributed to treatment.
      Significant effect of time was observed in the intake frequency of major food
      groups and calcium, vitamin A and C ( P <.001 for all), suggesting an equal
      effect of seasonality in both the groups. CONCLUSION: Addition of DFS in the diet
      improved dietary iron intake but did not affect the intake of energy, other
      nutrients, or nutritional status indicators. The improvement observed in the
      dietary iron intake demonstrates that fortification is an effective strategy to
      address iron deficiency in at-risk populations.

PMID- 28760008
TI  - Using an Expert Panel to Develop Social Support Program Sequencing for Young
      Adults With Type 1 Diabetes.
AB  - BACKGROUND: Young adults living with type 1 diabetes (T1DM) often encounter poor
      health outcomes, such as uncontrolled blood glucose levels. Social support
      programs can be a helpful method to support T1DM self-management. Effectively
      planning and tailoring social support programs for young adults living with T1DM
      are crucial for improving these programs and associated outcomes. OBJECTIVES:
      This study convened an expert panel primarily composed of young adults living
      with T1DM to generate ideas and key components for sequential inclusion in social
      support programs prioritizing them. METHOD: Exploratory expert panel meetings
      consisting of four individuals living with T1DM were held where Nominal Group
      Technique and Ideawriting exercises were used to develop themes and discussion
      points. RESULTS: Six themes emerged from the meetings representing areas of
      difficulty for young adults living with T1DM. Topics such as following self-care
      recommendations, nutrition, handling stress, coping with social situations, and
      navigating the health care system were identified as important issues facing
      young adults. CONCLUSIONS: By incorporating this approach into new or existing
      support group improved program discussions for young adults can be achieved and
      pertinent issues addressed, thus leading to improved health care outcomes.

PMID- 28760009
TI  - HIV-positive pregnant women attending the prevention of mother-to-child
      transmission of HIV/AIDS (PMTCT) services in Ethiopia: economic productivity
      losses across urban-rural settings.
AB  - HIV/AIDS impacts significantly on pregnant women and on children in Ethiopia.
      This impact has a multiplier effect on household economies and on productivity
      losses, and is expected to vary across rural and urban settings. Applying the
      human capital approach to data collected from 131 respondents, this study
      estimated productivity losses per HIV-positive pregnant woman-infant pair across
      urban and rural health facilities in Ethiopia, which in turn were used to
      estimate the national productivity loss. The study found that the annual
      productivity loss per woman-infant pair was Ethiopian birr (ETB) 7,433 or United
      States dollar (US$) 378 and ETB 625 (US$ 32) in urban and rural settings,
      respectively. The mean patient days lost per year due to inpatient admission at
      hospitals/health centres was 11 in urban and 22 in rural health facilities. On
      average, urban home care-givers spent 20 (SD = 21) days annually providing home
      care services, while their rural counterparts spent 23 days (SD = 26). The
      productivity loss accounted for 16% and 7% of household income in urban and rural
      settings, respectively. These high and varying productivity losses require
      preventive interventions that are appropriate to each setting to ensure the
      welfare of women and children in Ethiopia.

PMID- 28760010
TI  - Adherence and Persistence to Long-Acting Anticholinergics Treatment Episodes in
      Patients With Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: No studies have examined adherence or persistence to long-acting
      anticholinergics (LAAC) treatment episodes in patients with chronic obstructive
      pulmonary disease (COPD). OBJECTIVE: To estimate 1-year adherence and 5-year
      persistence to LAAC during treatment episodes, and the likelihood of initiating a
      subsequent treatment episode. METHODS: A retrospective cohort of LAAC-treated
      COPD patients was reconstructed from Quebec databases. A treatment episode was
      initiated at cohort entry, defined as the first LAAC prescription date on/after
      the first COPD diagnosis date recorded between October 1, 2003, and March 31,
      2014. We identified a subsequent treatment episode up to 5 years after the end of
      the episode initiated at cohort entry. We measured adherence as the proportion of
      days covered over 1 year. Persistence was defined as prescription renewal within
      90 days of the previous prescription and was plotted using Kaplan-Meier curves
      over 5 years. The 5-year hazard and cumulative incidence of initiating a
      subsequent episode were estimated with survival analyses. We compared adherence
      and persistence between the treatment episodes using t and log-rank tests.
      RESULTS: The cohort included 113 435 COPD patients. Adherence and persistence to
      LAAC were significantly lower in the subsequent treatment episode (55% vs 63%; P
      < 0.0001). The likelihood of initiating a subsequent episode was greatest
      immediately after the cessation of the initial episode, with 59% of patients
      starting a subsequent episode within 1 year. CONCLUSION: Adherence and
      persistence to LAAC were lower in the subsequent treatment episode. Interventions
      should be offered quickly after LAAC cessation.

PMID- 28760011
TI  - Boredom in patients with acquired brain injuries during inpatient rehabilitation:
      a scoping review.
AB  - PURPOSE: Boredom may impede engagement in inpatient rehabilitation following an
      acquired brain injury. This review aimed to: (1) describe the experience and (2)
      quantify the incidence of boredom; (3) identify measurement tools used to
      quantify boredom; (4) summarize factors contributing to boredom, and (5) outline
      evidence-based interventions shown to reduce boredom during inpatient
      rehabilitation. METHODS: Two researchers independently screened publications
      retrieved from electronic database searches. Publications presenting patient,
      carer or staff data relating to boredom in inpatients with acquired brain
      injuries were included. RESULTS: Two thousand four hundred and ninety-nine
      references were retrieved, 88 full texts were reviewed, with 24 studies included.
      The majority of studies reported qualitative data indicating boredom to be a
      common experience of patients with acquired brain injuries (n = 14 studies +1
      review). The incidence of boredom post acquired brain injury is unknown. Personal
      and organizational factors and the physical environment may contribute to boredom
      (n = 11 studies +2 reviews). Qualitative work (n = 9 studies) indicates that use
      of the creative-arts or exposure to environmental enrichment may help alleviate
      boredom in patients with acquired brain injuries during inpatient rehabilitation.
      CONCLUSION: Further mixed-methods research is required to establish the incidence
      of and contributing factors to boredom in patients with acquired brain injuries
      undergoing rehabilitation. Understanding this will help inform future research
      aimed at improving patient engagement in inpatient rehabilitation. Implications
      for rehabilitation Boredom is commonly reported by hospitalised patients with ABI
      to negatively affect their rehabilitation yet the scope of the problem has not
      been measured. Boredom is a complex phenomenon, likely influenced by a number of
      personal and environmental factors that are not fully understood in this
      population. Through a better understanding of boredom, interventions may be
      developed to improve patient engagement in inpatient rehabilitation programs.

PMID- 28760012
TI  - 2016 Annual Report of the ABPN.
AB  - The following is an edited version of the 2016 Report of the American Board of
      Psychiatry and Neurology, Inc. The full report can be obtained from the American
      Board of Psychiatry and Neurology ( www.abpn.com ).

PMID- 28760013
TI  - Maria Oquendo, M.D., Ph.D., 143rd President, 2016-2017.

PMID- 28760014
TI  - New Insights on the Treatment of Hypochondriasis.

PMID- 28760015
TI  - Smartphones for Smarter Care? Self-Management in Schizophrenia.

PMID- 28760016
TI  - Health Policy, Advocacy, and Public Education.

PMID- 28760017
TI  - Response to the Presidential Address.

PMID- 28760019
TI  - CORRECTION.

PMID- 28760020
TI  - Changes to the Diagnostic Criteria for Bipolar Disorder in DSM-5 Make Little
      Difference to Lifetime Diagnosis: Findings From the U.K. Bipolar Disorder
      Research Network (BDRN) Study.

PMID- 28760021
TI  - Calling for More Research of Medication Effects in Bipolar Disorder: Response to
      Ketter and Dell'Osso.

PMID- 28760022
TI  - Thomas Verner Moore.

PMID- 28760023
TI  - Treatment of Anxiety Disorders in Youths: Filling the Cup Further.

PMID- 28760024
TI  - Removing Firearms From the Home After Attempted Suicide Can Be Life Saving.

PMID- 28760025
TI  - Commentary on the Risk of Treatment-Emergent Mania With Methylphenidate in
      Bipolar Disorder.

PMID- 28760026
TI  - Amygdala-Guided Neurofeedback for Major Depression.

PMID- 28760027
TI  - Clinical and radiological outcomes of spinal endoscopic discectomy-assisted
      oblique lumbar interbody fusion: preliminary results.
AB  - OBJECTIVE Direct neural decompression cannot be achieved by performing lateral
      lumbar interbody fusion (LLIF). To overcome the indirect decompressive effect of
      LLIF, additional endoscopic discectomy with oblique lumbar interbody fusion
      (OLIF) has been attempted. The purpose of this study was to assess the clinical
      and radiological outcomes of patients who underwent OLIF with additional
      endoscopic discectomy. METHODS Spinal endoscopic discectomy-assisted OLIF was
      attempted to remove herniated disc material. Only patients with a follow-up time
      that exceeded 12 months were enrolled. Clinical parameters examined were the
      Oswestry Disability Index and visual analog scale scores of back and leg pain.
      Postoperative MRI was also performed. RESULTS Fourteen patients were enrolled.
      Central and foraminal disc herniations were evident in 8 and 6 patients,
      respectively. Concomitant central or foraminal herniated discs were removed
      completely after additional endoscopic discectomy, and disc removal was confirmed
      by postoperative MRI. Mean preoperative visual analog scale scores and Oswestry
      Disability Index scores improved postoperatively. CONCLUSIONS OLIF with
      additional endoscopic discectomy results in successful direct neural
      decompression without posterior decompressive procedures. Endoscopic assistance
      might overcome the limitations of LLIF.

PMID- 28760028
TI  - Correction of severe spinopelvic mismatch: decreased blood loss with lateral
      hyperlordotic interbody grafts as compared with pedicle subtraction osteotomy.
AB  - OBJECTIVE Pedicle subtraction osteotomy (PSO) provides extensive correction in
      patients with fixed sagittal plane imbalance but is associated with high
      estimated blood loss (EBL). Anterior column realignment (ACR) with lateral graft
      placement and sectioning of the anterior longitudinal ligament allows restoration
      of lumbar lordosis (LL). The authors compare peri- and postoperative measures in
      2 groups of patients undergoing correction of a sagittal plane imbalance, either
      through PSO or the use of lateral lumbar fusion and ACR with hyperlordotic (20
      degrees -30 degrees ) interbody cages, with stabilization through standard
      posterior instrumentation in all cases. METHODS The authors performed a
      retrospective chart review of cases involving a lumbar PSO or lateral lumbar
      interbody fusion and ACR (LLIF-ACR) between 2010 and 2015 at the authors'
      institution. Patients who had a PSO in the setting of a preexisting fusion that
      spanned more than 4 levels were excluded. Demographic characteristics,
      spinopelvic parameters, EBL, operative time, and LOS were analyzed and compared
      between patients treated with PSO and those treated with LLIF-ACR. RESULTS The
      PSO group included 14 patients and the LLIF-ACR group included 13 patients. The
      mean follow-up was 13 months in the LLIF-ACR group and 26 months in the PSO
      group. The mean EBL was significantly lower in the LLIF-ACR group, measuring
      approximately 50% of the mean EBL in the PSO group (1466 vs 2910 ml, p < 0.01).
      Total LL correction was equivalent between the 2 groups (35 degrees  in the PSO
      group, 31 degrees  in the LLIF-ACR group, p > 0.05), as was the preoperative PI
      LL mismatch (33 degrees  in each group, p > 0.05) and the postoperative PI-LL
      mismatch (< 1 degrees  in each group, p = 0.05). The fusion rate as assessed by
      the need for reoperation due to pseudarthrosis was lower in the LLIF-ACR group
      but not significantly so (3 revisions in the PSO group due to pseudarthrosis vs 0
      in the LLIF-ACR group, p > 0.5). The total operative time and LOS were not
      significantly different in the 2 groups. CONCLUSIONS This is the first direct
      comparison of the LLIF-ACR technique with the PSO in adult spinal deformity
      correction. The study demonstrates that the LLIF-ACR provides equivalent
      deformity correction with significantly reduced blood loss in patients with a
      previously unfused spine compared with the PSO. This technique provides a
      powerful means to avoid PSO in selected patients who require spinal deformity
      correction.

PMID- 28760029
TI  - Keyhole approaches to intradural pathologies.
AB  - OBJECTIVE Spinal tumors account for 2%-4% of all tumors of the central nervous
      system and can be intramedullary, intradural extramedullary, or extradural. In
      the past, wide approaches were used to obtain safe access to these tumors, as
      complete resection is the goal in treating most tumor entities. To reduce
      surgical complications due to large skin incisions and destabilizing
      laminectomies, minimally invasive approaches were established. In this study, the
      authors share their experience with mini-open approaches to intradural tumor
      pathologies. METHODS The authors retrospectively reviewed cases involving
      patients with intramedullary and intradural extramedullary lesions treated
      between 2009 and 2016. They present their surgical mini-open approach to the
      spinal cord as well as unique characteristics, key steps, and postsurgical
      complications for specific tumor subgroups (meningioma, neuroma, and
      intramedullary tumors). RESULTS A total of 245 intradural tumors were surgically
      treated during the study period. Of these lesions, 151 were intradural
      extramedullary meningiomas (n = 79) or neuromas (n = 72). Nine (12.5%) of the
      neuromas were dumbbell neuromas. Ninety-four tumors were intramedullary. The mean
      age of the patients was 51.4 years, and 53.9% were female. The mean duration of
      follow-up was 46.0 months. All meningiomas and neuromas could be resected using a
      mini-open keyhole approach, but only 5.3% of the intramedullary lesions could be
      accessed using this technique. Of the 94 patients with intramedullary tumors,
      76.6% required a laminotomy, 7.4% required a hemilaminectomy, and 10.6% required
      a 2-level laminectomy. Only 2 of the patients with intramedullary tumors needed
      stabilization for progressive cervical kyphosis during follow-up. None of the
      other patients developed spinal instability after undergoing surgery via the mini
      open (keyhole/interlaminar) approach. There were significantly more surgery
      associated complications in the large exposure group than in the patients treated
      with the mini-open approach (19.1% vs 9.6%, p < 0.01). CONCLUSIONS Intradural
      extramedullary and in selected cases intramedullary pathologies may safely be
      resected using a mini-open interlaminar approach. Avoiding laminectomy,
      laminotomy, and even hemilaminectomy preserves spinal stability and significantly
      reduces comorbidities, while still allowing for complete resection of these
      tumors.

PMID- 28760030
TI  - Cervical vertebroplasty for osteolytic metastases as a minimally invasive
      therapeutic option in oncological surgery: outcome in 14 cases.
AB  - OBJECTIVE The treatment of cervical spinal metastases represents a controversial
      issue regarding the type, extent, and invasiveness of interventions. In the
      lumbar and thoracic spine, kypho- and vertebroplasties have been established as
      minimally invasive procedures for patients with metastases to the vertebral
      bodies and without neurological deficit. These procedures show good results with
      respect to pain reduction and low complication rates. However, limited data are
      available for kypho- and vertebroplasties for cervical spinal metastases. In an
      effort to add to existing data, the authors here present a case series of 14
      patients who were treated for osteolytic metastases of the cervical spine using
      vertebroplasty alone or in addition to another surgical procedure involving the
      cervical spine in a palliative setting to reduce pain and restore stability.
      METHODS Fourteen patients consisting of 8 males and 6 females, with a mean age of
      64.7 years (range 44-85 years), were treated with vertebroplasty at the authors'
      clinic between January 2015 and November 2016. In total, 25 vertebrae were
      treated with vertebroplasty: 10 C-2, 5 C-3, 2 C-4, 2 C-5, 3 C-6, and 3 C-7. Two
      patients had an additional posterior stabilization and 5 patients an additional
      anterior stabilization. In 13 cases, the surgical approach was a modified Smith
      Robinson approach; in 1 case, the cement was injected into the corpus axis from
      posteriorly. Patients with osteolytic defects of the posterior wall of the
      vertebral body did not undergo surgery, nor did patients with neurological
      deficits. Preoperatively, on the 2nd day after surgery, and at the follow-up,
      neck pain was rated using the visual analog scale (VAS). RESULTS Twelve patients
      were examined at follow-up (mean 9 months). Neck pain was rated as a mean of 6.0
      (range 3-8) preoperatively, 2.9 on Day 2 after surgery (range 0-5), and 0.5 at
      the follow-up (range 0-4), according to the VAS. The mean Neck Disability Index
      at follow-up was 3.6% (range 0%-18%). CONCLUSIONS Anterior vertebroplasty of the
      cervical spine via an anterolateral approach represents a safe and minimally
      invasive procedure with a low complication rate and appears suitable for reducing
      pain and restoring stability in cases of cervical spinal metastases.
      Vertebroplasties can be combined with other anterior and posterior operations of
      the cervical spine and, in the axis vertebra, can be performed transpedicularly
      from posteriorly. Thus, in cases in which the posterior wall of the vertebral
      body is intact, vertebroplasty represents a less invasive alternative to
      vertebral replacement in oncological surgery. Prospective randomized trials with
      a longer follow-up period and a larger patient cohort are needed to confirm the
      encouraging results of this case series.

PMID- 28760031
TI  - Minimally invasive direct pars repair with cannulated screws and recombinant
      human bone morphogenetic protein: case series and review of the literature.
AB  - OBJECTIVE The objective of this study was to describe the use of a minimally
      invasive surgical treatment of lumbar spondylolysis in athletes by a
      fluoroscopically guided direct pars screw placement with recombinant human bone
      morphogenetic protein-2 (rhBMP-2) and to report on clinical and radiographic
      outcomes. METHODS A retrospective review was conducted of all patients treated
      surgically for lumbar spondylolysis via a minimally invasive direct pars repair
      with cannulated screws. Demographic information, clinical features of
      presentation, perioperative and intraoperative radiographic imaging, and
      postoperative data were collected. A 1-cm midline incision was performed for the
      placement of bilateral pars screws utilizing biplanar fluoroscopy, followed by
      placement of a fully threaded 4.0-mm-diameter titanium cannulated screw. A
      tubular table-mounted retractor was utilized for direct pars fracture
      visualization and debridement through a separate incision. The now-visualized
      pars fracture could then be decorticated, with care taken not to damage the
      titanium screw when using a high-speed drill. Local bone obtained from the
      curettage was then placed in the defect with 1.05 mg rhBMP-2 divided equally
      between the bilateral pars defects. RESULTS Nine patients were identified (mean
      age 17.7 +/- 3.42 years, range 14-25 years; 6 male and 3 female). All patients
      had bilateral pars fractures of L-4 (n = 4) or L-5 (n = 5). The mean duration of
      preoperative symptoms was 17.22 +/- 13.2 months (range 9-48 months). The mean
      operative duration was 189 +/- 29 minutes (range 151-228 minutes). The mean
      intraoperative blood loss was 17.5 +/- 10 ml (range 10-30 ml). Radiographic
      follow-up was available in all cases; the mean length of time from surgery to the
      most recent imaging study was 30.8 +/- 23.3 months (range 3-59 months). The mean
      hospital length of stay was 1.13 +/- 0.35 days (range 1-2 days). There were no
      intraoperative complications. CONCLUSIONS Lumbar spondylolysis treatment with a
      minimally invasive direct pars repair is a safe and technically feasible option
      that minimizes muscle and soft-tissue dissection, which may particularly benefit
      adolescent patients with a desire to return to a high level of physical activity.

PMID- 28760032
TI  - Minimally invasive transforaminal lumbar interbody fusion with expandable versus
      static interbody devices: radiographic assessment of sagittal segmental and
      pelvic parameters.
AB  - OBJECTIVE Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF)
      has been adopted as an alternative technique to hasten recovery and minimize
      postoperative morbidity. Advances in instrumentation technologies and operative
      techniques have evolved to maximize patient outcomes as well as radiographic
      results. The development of expandable interbody devices allows a surgeon to
      perform MIS-TLIF with minimal tissue disruption. However, sagittal segmental and
      pelvic radiographic outcomes after MIS-TLIF with expandable interbody devices are
      not well characterized. The object of this study is to evaluate the radiographic
      sagittal lumbar segmental and pelvic parameter outcomes of MIS-TLIF performed
      using an expandable interbody device. METHODS A retrospective review of MIS-TLIFs
      performed between 2014 and 2016 at a high-volume center was performed.
      Radiographic measurements were performed on lateral radiographs before and after
      MIS-TLIF with static or expandable interbody devices. Radiographic measurements
      included disc height, foraminal height, fused disc angle, lumbar lordosis, pelvic
      incidence, sacral slope, and pelvic tilt. Mismatch between pelvic incidence and
      lumbar lordosis were calculated for each radiograph. RESULTS A total of 48 MIS
      TLIFs were performed, predominantly at the L4-5 level, in 44 patients. MIS-TLIF
      with an expandable interbody device led to a greater and more sustained increase
      in disc height when compared with static interbody devices. Foraminal height
      increased after MIS-TLIF with expandable but not with static interbody devices.
      MIS-TLIF with expandable interbody devices increased index-level segmental
      lordosis more than with static interbody devices. The increase in segmental
      lordosis was sustained in the patients with expandable interbody devices but not
      in patients with static interbody devices. For patients with a collapsed disc
      space, MIS-TLIF with an expandable interbody device provided superior and longer
      lasting increases in disc height, foraminal height, and index-level segmental
      lordosis than in comparison with patients with static interbody devices. Using an
      expandable interbody device improved the Oswestry Disability Index scores more
      than using a static interbody device, and both disc height and segmental lordosis
      were correlated with improved clinical outcome. Lumbar MIS-TLIF with expandable
      or static interbody devices had no effect on overall lumbar lordosis, pelvic
      parameters, or pelvic incidence-lumbar lordosis mismatch. CONCLUSIONS Performing
      MIS-TLIF with an expandable interbody device led to a greater and longer-lasting
      restoration of disc height, foraminal height, and index-level segmental lordosis
      than MIS-TLIF with a static interbody device, especially for patients with a
      collapsed disc space. However, neither technique had any effect on radiographic
      pelvic parameters.

PMID- 28760033
TI  - Minimally invasive guidewireless, navigated pedicle screw placement: a technical
      report and case series.
AB  - OBJECTIVE Percutaneous pedicle screw insertion (PPSI) is a mainstay of minimally
      invasive spinal surgery. Traditionally, PPSI is a fluoroscopy-guided, multistep
      process involving traversing the pedicle with a Jamshidi needle, placement of a
      Kirschner wire (K-wire), placement of a soft-tissue dilator, pedicle tract
      tapping, and screw insertion over the K-wire. This study evaluates the accuracy
      and safety of PPSI with a simplified 2-step process using a navigated awl-tap
      followed by navigated screw insertion without use of a K-wire or fluoroscopy.
      METHODS Patients undergoing PPSI utilizing the K-wire-less technique were
      identified. Data were extracted from the electronic medical record. Complications
      associated with screw placement were recorded. Postoperative radiographs as well
      as CT were evaluated for accuracy of pedicle screw placement. RESULTS Thirty-six
      patients (18 male and 18 female) were included. The patients' mean age was 60.4
      years (range 23.8-78.4 years), and their mean body mass index was 28.5 kg/m2
      (range 20.8-40.1 kg/m2). A total of 238 pedicle screws were placed. A mean of 6.6
      pedicle screws (range 4-14) were placed over a mean of 2.61 levels (range 1-7).
      No pedicle breaches were identified on review of postoperative radiographs. In a
      subgroup analysis of the 25 cases (69%) in which CT scans were performed, 173
      screws were assessed; 170 (98.3%) were found to be completely within the pedicle,
      and 3 (1.7%) demonstrated medial breaches of less than 2 mm (Grade B). There were
      no complications related to PPSI in this cohort. CONCLUSIONS This streamlined 2
      step K-wire-less, navigated PPSI appears safe and accurate and avoids the need
      for radiation exposure to surgeon and staff.

PMID- 28760034
TI  - Complete anatomic reduction and monosegmental fusion for lumbar spondylolisthesis
      of Grade II and higher: use of the minimally invasive "rocking" technique.
AB  - OBJECTIVE Different surgical approaches have been described for treatment of
      spondylolisthesis, including in situ fusions, reductions of various degrees, and
      inclusion of healthy adjacent segments into the fusion construct. To the authors'
      knowledge, there are only sparse reports describing consistent complete reduction
      and monosegmental transforaminal lumbar interbody fusion for spondylolisthesis
      using a minimally invasive technique. The authors assess the efficacy of this
      technique in the reduction of local deformity and correction of overall sagittal
      profile in single-level spondylolisthesis. METHODS This cohort study consists of
      a total of 36 consecutive patients treated over a period of 6 years. Patients
      with varying grades of lumbar spondylolisthesis (29 Meyerding Grade II and 7
      Meyerding Grade III) were treated with operative reduction via minimally invasive
      transforaminal lumbar interbody fusion (MIS-TLIF) in which the "rocking"
      technique was used. The clinical outcomes were measured using the visual analog
      scale (VAS) for pain and the Revised Oswestry Disability Index (ODI) for low-back
      pain/dysfunction. Meyerding grade, pelvic incidence (PI), lumbar lordosis (LL),
      disc space angle (DSA), pelvic tilt (PT), and sacral slope (SS) were assessed to
      measure the radiological outcomes. These were reviewed for each patient for a
      minimum of 2 years. RESULTS At most recent follow-up, 94% of patients were pain
      free. There were 2 patients (6%) who had moderate pain (which corresponded to
      higher-grade of listhesis), but all showed an improvement in pain scores (p <
      0.05). The mean VAS score improved from 6.5 (SD 1.5) preoperatively to 1.6 (SD
      1.3) and the mean ODI score improved from 53.7 (SD 13.1) preoperatively to 22.5
      (SD 15.5) at 2-year follow-up. All radiological parameters improved following
      surgery. Most significant improvement was noted for LL, DSA, and SS. Both LL and
      SS were found to decrease, while DSA increased postoperatively. PI remained
      relatively unchanged, while PT showed a mild increase, which was not significant.
      Good fusion was achieved with implants in situ at 2-year follow-up. A 100%
      complete reduction of all grades of spondylolisthesis was achieved. The overall
      sagittal profile improved dramatically. No major perioperative complications were
      encountered. CONCLUSIONS Minimally invasive monosegmental TLIF for
      spondylolisthesis reduction using this rocking technique is effective in the
      treatment of various grades of spondylolisthesis. Consistent complete reduction
      of the slippage as well as excellent correction of overall sagittal profile can
      be achieved, and the need for including healthy adjacent segments in the fusion
      construct can be avoided.

PMID- 28760036
TI  - Tubular microdiscectomy: techniques, complication avoidance, and review of the
      literature.
AB  - OBJECTIVE Microendoscopic discectomy is a minimally invasive surgery technique
      that was initially described in 1997. It allows surgeons to work with 2 hands
      through a small-diameter, operating table-mounted tubular retractor, and to apply
      standard microsurgical techniques in which a small skin incision and minimal
      muscle dissection are used. Whether the surgeon chooses to use an endoscope or a
      microscope for visualization, the technique uses the same type of retractor and
      is thus called tubular microdiscectomy. The goal in this study was to review the
      current literature, examine the level of evidence supporting tubular
      microdiscectomy, and describe surgical techniques for complication avoidance.
      METHODS The authors performed a systematic PubMed review using the terms
      "microdiscectomy trial," "tubular and open microdiscectomy," "microendoscopic
      open discectomy," and "minimally invasive open microdiscectomy OR
      microdiskectomy." Of 317 references, 10 manuscripts were included for analysis
      based on study design, relevance, and appropriate comparison of open to tubular
      discectomy. RESULTS Similar and very favorable clinical outcomes can be expected
      from tubular and standard microdiscectomy. Studies have demonstrated equivalent
      operating times for both procedures, with lower blood loss and shorter hospital
      stays associated with tubular microdiscectomy. Furthermore, postoperative
      analgesic usage has been shown to be significantly lower after tubular
      microdiscectomy. Overall rates of complications are no different for tubular and
      standard microdiscectomy. CONCLUSIONS Prospective randomized trials have been
      used to evaluate outcomes of common minimally invasive lumbar spine procedures.
      For lumbar discectomy, Level I evidence supports equivalently good outcomes for
      tubular microdiscectomy compared with standard microdiscectomy. Likewise, Level I
      data indicate similar safety profiles and may indicate lower blood loss for
      tubular microdiscectomy. Future studies should examine the comparative value of
      these procedures.

PMID- 28760037
TI  - Mini-open anterior approach for cervicothoracic junction fracture: technical
      note.
AB  - Elderly patients with diffuse idiopathic skeletal hyperostosis are at high risk
      for falls, and 3-column unstable fractures present multiple challenges. Unstable
      fractures across the cervicothoracic junction are associated with significant
      morbidity and require fixation, which is commonly performed through a posterior
      open or percutaneous approach. The authors describe a novel, navigated, mini-open
      anterior approach using intraoperative cone-beam CT scanning to place lag screws
      followed by an anterior plate in a 97-year-old patient. This approach is less
      invasive and faster than an open posterior approach and can be considered as an
      option for management of cervicothoracic junction fractures in elderly patients
      with high perioperative risk profile who cannot tolerate being placed prone
      during surgery.

PMID- 28760035
TI  - Minimally invasive versus open fusion for Grade I degenerative lumbar
      spondylolisthesis: analysis of the Quality Outcomes Database.
AB  - OBJECTIVE Lumbar spondylolisthesis is a degenerative condition that can be
      surgically treated with either open or minimally invasive decompression and
      instrumented fusion. Minimally invasive surgery (MIS) approaches may shorten
      recovery, reduce blood loss, and minimize soft-tissue damage with resultant
      reduced postoperative pain and disability. METHODS The authors queried the
      national, multicenter Quality Outcomes Database (QOD) registry for patients
      undergoing posterior lumbar fusion between July 2014 and December 2015 for Grade
      I degenerative spondylolisthesis. The authors recorded baseline and 12-month
      patient-reported outcomes (PROs), including Oswestry Disability Index (ODI), EQ
      5D, numeric rating scale (NRS)-back pain (NRS-BP), NRS-leg pain (NRS-LP), and
      satisfaction (North American Spine Society satisfaction questionnaire).
      Multivariable regression models were fitted for hospital length of stay (LOS), 12
      month PROs, and 90-day return to work, after adjusting for an array of
      preoperative and surgical variables. RESULTS A total of 345 patients (open
      surgery, n = 254; MIS, n = 91) from 11 participating sites were identified in the
      QOD. The follow-up rate at 12 months was 84% (83.5% [open surgery]; 85% [MIS]).
      Overall, baseline patient demographics, comorbidities, and clinical
      characteristics were similarly distributed between the cohorts. Two hundred fifty
      seven patients underwent 1-level fusion (open surgery, n = 181; MIS, n = 76), and
      88 patients underwent 2-level fusion (open surgery, n = 73; MIS, n = 15).
      Patients in both groups reported significant improvement in all primary outcomes
      (all p < 0.001). MIS was associated with a significantly lower mean
      intraoperative estimated blood loss and slightly longer operative times in both 1
      and 2-level fusion subgroups. Although the LOS was shorter for MIS 1-level
      cases, this was not significantly different. No difference was detected with
      regard to the 12-month PROs between the 1-level MIS versus the 1-level open
      surgical groups. However, change in functional outcome scores for patients
      undergoing 2-level fusion was notably larger in the MIS cohort for ODI (-27 vs 
      16, p = 0.1), EQ-5D (0.27 vs 0.15, p = 0.08), and NRS-BP (-3.5 vs -2.7, p =
      0.41); statistical significance was shown only for changes in NRS-LP scores (-4.9
      vs -2.8, p = 0.02). On risk-adjusted analysis for 1-level fusion, open versus
      minimally invasive approach was not significant for 12-month PROs, LOS, and 90
      day return to work. CONCLUSIONS Significant improvement was found in terms of all
      functional outcomes in patients undergoing open or MIS fusion for lumbar
      spondylolisthesis. No difference was detected between the 2 techniques for 1
      level fusion in terms of patient-reported outcomes, LOS, and 90-day return to
      work. However, patients undergoing 2-level MIS fusion reported significantly
      better improvement in NRS-LP at 12 months than patients undergoing 2-level open
      surgery. Longer follow-up is needed to provide further insight into the
      comparative effectiveness of the 2 procedures.

PMID- 28760038
TI  - Fully endoscopic lumbar interbody fusion using a percutaneous unilateral biportal
      endoscopic technique: technical note and preliminary clinical results.
AB  - OBJECTIVE Minimally invasive spine surgery can minimize damage to normal
      anatomical structures. Recently, fully endoscopic spine surgeries have been
      attempted for lumbar fusion surgery. In this study, the authors performed a
      percutaneous unilateral biportal endoscopic (UBE) technique as a minimally
      invasive surgery for lumbar fusion. The purpose of this study is to present the
      UBE technique of fully endoscopic lumbar interbody fusion (LIF) and to analyze
      the clinical results. METHODS Patients who were to undergo single-level fusion
      surgery from L3-4 to L5-S1 were enrolled. Two channels (endoscopic portal and
      working portal) were used for endoscopic lumbar fusion surgery. All patients
      underwent follow-up for more than 12 months. Demographic characteristics,
      diagnosis, operative time, and estimated blood loss were evaluated. MRI was
      performed on postoperative Day 2. Clinical evaluations (visual analog scale [VAS]
      for the leg and Oswestry Disability Index [ODI] scores) were performed
      preoperatively and during the follow-up period. RESULTS A total of 69 patients
      (24 men and 45 women) were enrolled in this study. The mean follow-up period was
      13.5 months. Postoperative MRI revealed optimal direct neural decompression after
      fully endoscopic fusion surgery. VAS and ODI scores significantly improved after
      the surgery. There was no postoperative neurological deterioration. CONCLUSIONS
      Fully endoscopic LIF using the UBE technique may represent an alternative
      minimally invasive LIF surgery for the treatment of degenerative lumbar disease.
      Long-term follow-up and larger clinical studies are needed to validate the
      clinical and radiological results of this surgery.

PMID- 28760039
TI  - Neuronavigation and 3D fluoroscopy-guided lag screw reduction and osteosynthesis
      for traumatic spondylolistheses of the axis: a path worth exploring?
AB  - OBJECTIVE In traumatic spondylolistheses of the axis, there is a marked
      heterogeneity of the observed injury patterns, with a wide range of the severity
      from stable fractures, which can be treated conservatively with very good
      success, to highly unstable fractures, which should be treated surgically. A
      number of classification systems have been devised to assess the instability of
      the injuries and to derive a corresponding therapy recommendation. In particular,
      the results and recommendations regarding medium-severity cases are still
      inconclusive. Minimally invasive percutaneous procedures performed using modern
      techniques such as 3D fluoroscopy and neuronavigation have the potential for
      improvements in the therapeutic outcome and procedural morbidity against open
      surgical procedures and conservative therapy. METHODS A minimally invasive method
      using 3D fluoroscopy and neuronavigation for percutaneous lag screw
      osteosynthesis of the pars interarticularis was performed in 12 patients with a
      Levine-Edwards Type II fracture. Ten patients had an isolated hangman's fracture
      and 2 patients had an additional odontoid fracture of the axis (Type II according
      to the Anderson and D'Alonzo classification system). Complications, operating
      parameters, screw positions, and bony fusion were evaluated for the description
      and evaluation of the technique. RESULTS In 6 men and 6 women, percutaneous lag
      screw osteosynthesis was performed successfully. Correct placement could be
      verified postoperatively for all inserted screws. In the case series, nonunion
      was not observed. In all patients with a complete follow-up, a bony fusion, an
      intact vertebral alignment, and no deformity could be detected on CT scans
      obtained after 3 months. CONCLUSIONS The percutaneous pars interarticularis lag
      screw osteosynthesis is a minimally invasive and mobility-preserving surgical
      technique. Its advantages over alternative methods are its minimal invasiveness,
      a shortened treatment time, and high fusion rates. The benefits are offset by the
      risk of injury to the vertebral arteries. The lag screw osteosynthesis is only
      possible with Levine-Edwards Type II fractures, because the intervertebral joints
      to C-3 are functionally preserved. A further development and evaluation of the
      operative technique as well as comparison with conservative and alternative
      surgical treatment options are deemed necessary.

PMID- 28760040
TI  - Stereotactic navigation for the prepsoas oblique lateral lumbar interbody fusion:
      technical note and case series.
AB  - The prepsoas retroperitoneal approach is a minimally invasive technique used for
      anterior lumbar interbody fusion. The approach may have a more favorable risk
      profile than the transpsoas approach, decreasing the risks that come with
      dissecting through the psoas muscle. However, the oblique angle of the spine in
      the prepsoas approach can be disorienting and challenging. This technical report
      provides an overview of the use of navigation in prepsoas oblique lateral lumbar
      interbody fusion in a series of 49 patients.

PMID- 28760041
TI  - Editorial. Nuances of restoration of lumbar lordosis using an MIS anterior column
      release versus posterior 3-column osteotomy.

PMID- 28760042
TI  - Introduction. Minimally invasive spine surgery.

PMID- 28760043
TI  - Erratum: "Polygonum multiflorum Decreases Airway Allergic Symptoms in a Murine
      Model of Asthma".

PMID- 28760046
TI  - Comment on: "A comprehensive model for heat-induced radio sensitization" by
      Bruninck et al. on Int. J. of Hyperthermia. 2017 Jun 23:1-19.

PMID- 28760044
TI  - Baicalein Preventive Treatment Confers Optimal Cardioprotection by PTEN/Akt/NO
      Activation.
AB  - Baicalein is a flavonoid with excellent oxidant scavenging capability. It has
      been reported to protect against a variety of oxidative injuries including
      ischemia/reperfusion (I/R). However, the optimal treatment strategy for I/R
      injury and the protective mechanisms are not fully understood. In this study we
      employed an established chick cardiomyocyte model of I/R and investigated the
      effects of three baicalein treatment strategies on reactive oxygen species (ROS)
      scavenging, nitric oxide (NO) production and cell viability. The molecular
      signaling pathways were also explored. Compared to the I/R control (cell death
      52.2[Formula: see text][Formula: see text][Formula: see text]2.0%), baicalein
      preventive treatment (25[Formula: see text][Formula: see text]M, pretreated for
      72[Formula: see text]h and continued through I/R) conferred the best protection
      (19.5[Formula: see text][Formula: see text][Formula: see text]3.9%, [Formula: see
      text]), followed by I/R treatment (treated during I/R) and reperfusion treatment
      (treated at reperfusion only). Preventive and I/R treatments almost completely
      abolished ROS generation during both ischemic and reperfusion phases, and
      increased NO production and Akt phosphorylation. Reperfusion treatment reduced
      the ROS burst in the early reperfusion phase only, and had no effect on NO
      production and Akt activation. Further, the phosphorylation of phosphatase and
      tensin homolog (PTEN), a phosphatase negatively regulating Akt activation, was
      significantly increased by baicalein preventive treatment and slightly by the I/R
      treatment. PTEN protein expression was reduced in the same trend accordingly.
      Baicalein reperfusion treatment had no effects on PTEN phosphorylation and
      expression. Our results indicate that baicalein preventive treatment confers
      optimal cardioprotection against I/R injury, and this protection involves
      effective oxidant scavenging and the activation of PTEN/Akt/NO pathway.

PMID- 28760045
TI  - Hodgkin lymphoma in children, adolescents and young adults - a comparative study
      of clinical presentation and treatment outcome.
AB  - BACKGROUND: Hodgkin lymphoma (HL) treatment protocols for children, adolescents
      and young adults traditionally differ, but the biological and clinical
      justification for this remains uncertain. MATERIAL AND METHODS: We compared age
      dependent clinical presentation and treatment and outcome for 1072 classical HL
      patients 0-24 years diagnosed in Denmark (1990-2010) and Sweden (1992-2009) in
      pediatric (n = 315, Denmark <15 years, Sweden <18 years) or adult departments (n
      = 757). Distribution of clinical characteristics was assessed with Pearson's chi2
      test and Mantel-Haenszel trend test. The Kaplan-Meier method was used for
      survival analyses. Hazard ratios (HR) were used to compare the different
      treatment groups and calculated using Cox regression. RESULTS: Children (0-9
      years) less often presented with advanced disease than adolescents (10-17 years)
      and young adults (18-24 years) (stage IIB-IV: children 32% vs. adolescents 50%,
      and adults 55%; p < .005). No variation in overall survival (OS) was seen between
      pediatric and adult departments or by country. Danish pediatric patients received
      radiotherapy (36%) less frequently than Swedish pediatric patients (71%) (p <
      .0001). Ten-year event-free survival (EFS) was lower among Danish pediatric
      patients (0-14 years) (0.79; 95% confidence interval (CI) 0.70-0.86) than among
      Swedish pediatric patients (0-17 years) (0.88; 95% CI 0.83-0.92), HR (1.93; 95%
      CI 1.08-3.46). A similar pattern was seen between adult patients in the two
      countries: Denmark 10-year EFS 0.85 (95% CI 0.81-0.88), Sweden 0.88 (95% CI 0.84
      0.91), adjusted HR 1.51 (95% CI 1.03-2.22). CONCLUSION: Adolescents and young
      adults shared similar clinical presentation suggesting a rationale of harmonized
      treatment for these groups. Both adult and pediatric protocols provided high OS
      with no significant difference between the departments. The less frequent use of
      radiotherapy in Danish pediatric patients corresponded to a lower EFS, but
      comparable OS in all groups confirmed effective rescue strategies for the
      relapsing patients.

PMID- 28760047
TI  - Demographics, treatment patterns, and healthcare utilization and cost of
      repository corticotropin injection in patients with systemic lupus erythematosus
      or rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate healthcare resource utilization (HRU) and costs among
      patients who initiated repository corticotropin injection (RCI; H.P. Acthar Gel)
      treatment for rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).
      METHODS: Patients aged >=18 years with >=2 diagnoses for either RA or SLE between
      July 1, 2006 and April 30, 2015 were identified in the HealthCore Integrated
      Research Database. Index RCI date was the earliest date of a medical or pharmacy
      claim for RCI after diagnosis. Baseline characteristics, pre- and post-initiation
      HRU and costs were assessed using descriptive statistics. RESULTS: This study
      identified 180 RA patients (mean age = 60 years, 56% female) and 29 SLE patients
      (mean age = 45 years, 90% female) who initiated RCI. First RCI use averaged 7.1
      and 22.6 months after the initial RA and SLE diagnosis, respectively. After RCI
      initiation, RA patients incurred significantly lower per-patient-per-month (PPPM)
      all-cause medical costs ($1,881 vs $682, p < .01) vs the pre-initiation period,
      driven by lower PPPM hospitalizations costs ($1,579 vs $503, p < .01). Overall
      PPPM healthcare costs were higher ($2,751 vs $5,487, p < .01) due to higher PPPM
      prescription costs ($869 vs $4,805, p < .01). Similarly, SLE patients had
      decreased PPPM hospitalization costs ($3,192 vs $799, p = .04) and increased PPPM
      prescription costs ($905 vs $7,443, p < .01) after initiating RCI; the difference
      in overall PPPM healthcare costs was not statistically significant likely, due to
      small sample size. CONCLUSION: This study, across a heterogeneous population of
      variable disease duration, described clinical and healthcare utilization and
      costs of RA and SLE patients initiating RCI in a real-world setting. We observed
      that patients receiving RCI had lower utilization and costs for medical services
      in both disease populations, which partially offset the increased prescription
      costs by 30% and 37%. Future research is needed to explore factors associated
      with RCI initiation and its impact on long-term outcomes.

PMID- 28760049
TI  - Recurrent postcoital vesicovaginal fistula: outcome of consensual sex in an adult
      female.

PMID- 28760048
TI  - Protective effect of alpha-linolenic acid on gentamicin-induced ototoxicity in
      mice.
AB  - Alpha-linolenic acid is one of the fatty acids known as omega 3. Previous studies
      have shown the antioxidant and anti-inflammatory effects of alpha-linolenic acid,
      which prevented cell damage by inhibiting apoptotic pathway. Also, it is known
      that gentamicin activates apoptotic mediators and causes necrosis in the kidney.
      Due to this reason, we planned a study to evaluate the protective effects of
      alpha-linolenic acid on gentamicin induced ototoxicity by evaluating inflammation
      and apoptotic mediators. For this purpose, 100 mg/kg gentamicin (i.p;
      intraperitoneally) and 200 mg/kg alpha-linolenic acid (gavage) are administered
      to mice for 9 days. On 9th and 10th days, rotarod performance was assessed to
      test the effect of gentamicin and alpha-linolenic acid treatment on the motor
      coordination of mice. Gentamicin treatment decreased fall latency of mice and
      gentamicin treatment together with alpha-linolenic acid increased fall latency of
      mice. Gentamicin treatment also increased expression of phospholipase A2(plA2),
      cyclooxygenase-2(COX-2) and inducible nitric oxide syntheses (iNOS). Furthermore,
      it increased Bax and caspase-3, which are proapoptotic proteins and decreased bcl
      2 that is an antiapoptotic protein. Gentamicin treatment together alpha-linolenic
      acid recovered the change of expression of these enzymes. In conclusion, this
      study showed that alpha-linolenic acid will be useful to prevent gentamicin
      induced ototoxicity by inhibiting apoptosis and inflammation.

PMID- 28760050
TI  - Inside-out: the role of anger experience and expression in the development of
      postpartum mood disorders.
AB  - PURPOSE: Among negative emotions, anger has not been studied in as much depth in
      her connection to postpartum mood disorders. The study aimed to investigate the
      role of anger as a potential vulnerability factor increasing the risk of
      Maternity Blues (MB) and Postpartum Depression (PPD). MATERIALS AND METHODS:
      Pregnant women in their third trimester of pregnancy underwent the following
      tests: the State Trait Anger Expression Inventory 2 - STAXI-2 (baseline visit),
      the Blues Questionnaire -BQ (3 and 5 days after delivery), and the Edinburgh
      Postnatal Depression Scale (EPDS) (3 and 6 months following delivery). RESULTS:
      One hundred ten subjects were included in this study. The prevalence rate of
      mothers with MB was about 35%, whereas about 4% of women developed a PPD.
      Significant positive correlations were found among State anger (SANG), Trait
      anger (TANG), anger expression out (AXO) and in (AXI) and postpartum depressive
      disorders, as measured by blues questionnaire (BQ) and EPDS. CONCLUSIONS: Anger
      experience and expression can be considered as vulnerability factors for
      postpartum mood disorders onset. Particularly, the expression of angry feelings
      toward other persons or objects in the environment (AXO) predicts the onset of
      MB, whereas holding in or suppressing angry feelings (AXI) could be a risk factor
      for subsequent PPD.

PMID- 28760051
TI  - How assistive devices affect activities of daily living and cognitive functions
      of people with brain injury: a meta-analysis.
AB  - PURPOSE: This study aims to systematically evaluate and synthesize the literature
      on the effects of assistive technology devices on the activities of daily living
      and cognitive functions of people with brain injury. METHODS: Eight randomized
      controlled trials were selected from online databases pertaining to the
      scientific use of AT devices for people with brain injury. The Jadad scale was
      used to analyse the subjects qualitatively, and Comprehensive Meta-Analysis 2.0
      was used to test the statistical heterogeneity, effect size, sensitivity and
      publication bias of each of the selected studies. RESULTS: All selected studies
      were assigned a score of three on the Jadad scale, which could classify them as
      high-quality studies. The total number of participants in the studies was 385.
      The effect size of activities of daily living was 0.72, which is a medium effect
      size and that of cognitive function was 0.30, which is a small effect size.
      CONCLUSION: Assistive devices are effective in improving the activities of daily
      living and relatively less effective in enhancing the cognitive function of
      people with brain injury. This meta-analysis is evidence that assistive devices
      could be an effective intervention method for people with brain injury.
      Implications for Rehabilitation The purpose of this study is to demonstrate the
      effectiveness of this approach and to generalize the use of assistive devices. We
      aim to provide a basis for popularizing assistive devices as a therapeutic
      intervention method.

PMID- 28760052
TI  - Primary hyperparathyroidism in pregnancy treated with cinacalcet: a case report.

PMID- 28760053
TI  - Pseudoaneurysm: really a placenta-associated vascular regression abnormality?

PMID- 28760054
TI  - Successful treatment of a patient with acute promyelocytic leukemia with a
      STAT5B/RARA fusion gene using decitabine.

PMID- 28760055
TI  - Efficacy of caesarean scar defect repair in improving postmenstrual bleeding and
      factors associated with poor effect.
AB  - Caesarean scar defect (CSD) can cause postmenstrual bleeding. Defect repair is an
      effective technique to improve this symptom, but there are still a few patients
      getting little improvement. This retrospective study evaluates the efficacy of
      scar repair and explores the factors associated with poor effect. In total, 123
      patients were involved in the final analysis. All of them complained about
      menstruation period >7 days due to postmenstrual bleeding. Before surgery, 87.8%
      of patients had a menstruation period more than 10 days and 20.3% had a period
      more than 15 days. After surgery, a normal menstruation period (< =7 days) was
      achieved in 46.3% (95%CI 37.3%-55.6%) of patients and a menstruation period
      lasting no more than 10 days was achieved in 74.8% (95%CI 66.2%-82.2%). Through
      multivariate logistic analysis, four factors were found dependently associated
      with poor effect (defined as menstruation period >10 days after surgery):
      repeated caesarean section (OR 9.75, 95%CI 2.30-41.36, 0.002) was a risk factor,
      while defect volume >600 mm3 (OR 0.14, 95%CI 0.03-0.56, 0.006), interval from
      caesarean section to symptom emerging >3 months (OR 0.25, 95%CI 0.07-0.94, 0.041)
      and straight or retroflexed uterus (OR 0.19, 95%CI 0.05-0.79, 0.022) were
      protective factors. Impact statement What is already known on this subject?
      Caesarean scar defect can cause postmenstrual bleeding. Defect repair can improve
      this symptom, but there are still a few patients getting little improvement after
      surgery. What do the results of this study add? Defect volume >600 mm3, interval
      from caesarean section to symptom emerging >3 months and straight or retroflexed
      uterus are protective factors of poor effect (defined as menstruation period >10
      days after surgery), and repeated caesarean section is a risk factor. What are
      the implications of these findings for clinical practice and/or further research?
      These findings may help in counselling the patients and in medical decision.
      Further researches are needed to explore other factors associated with surgical
      effect and build prediction models.

PMID- 28760056
TI  - Cost per additional responder for ixekizumab and other FDA-approved biologics in
      moderate-to-severe plaque psoriasis.
AB  - BACKGROUND: Evidence of the cost-efficacy of ixekizumab for the treatment of
      moderate-to-severe plaque psoriasis (PsO) in the US is limited. OBJECTIVE: To
      estimate the number needed to treat (NNT) and monthly cost of achieving one
      additional Psoriasis Area and Severity Index (PASI) 75, 90, and 100 responder for
      ixekizumab and other Food and Drug Administration (FDA)-approved biologics in
      PsO. METHODS: A network meta-analysis estimated the probability of achieving PASI
      75, 90, or 100 response during induction for each biologic. NNTs were calculated
      using response difference of each respective biologic vs placebo at the end of
      induction. Monthly costs per additional PASI responder were based on FDA-approved
      doses, wholesale acquisition costs, and induction NNTs. RESULTS: Induction NNTs
      for ixekizumab 80 mg once every 2 weeks (Q2W) relative to placebo were
      consistently lower across all levels of clearance compared with the other
      biologics. Monthly cost per additional responder was lowest for ustekinumab 45 mg
      at PASI 75 and for secukinumab 300 mg and ixekizumab 80 mg Q2W at PASI 90.
      Ixekizumab 80 mg Q2W had the lowest cost for PASI 100. CONCLUSION: In this
      analysis, ixekizumab is the most cost-efficient biologic in the US when targeting
      complete resolution, as measured by PASI 100 in PsO.

PMID- 28760057
TI  - Foetal outcomes after exposure to albendazole in early pregnancy.

PMID- 28760058
TI  - The effect of video information on anxiety levels in women attending colposcopy:
      a randomized controlled trial.
AB  - OBJECTIVE: The aim was to investigate whether additional information, in video
      form, reduces anxiety, depression and pain levels in women referred for
      colposcopy. MATERIAL AND METHODS: Between September 2012 and March 2015, 136
      patients referred for colposcopy were randomized into two study arms. Group A
      received video information in addition to the regular information leaflet, and
      group B (control group) received only the regular information leaflet. The
      patients were requested to complete standardized online questionnaires. The first
      online questionnaire (T1) was pre-randomization, and was completed at home, 5
      days prior to the appointment. The second online questionnaire (T2) was completed
      directly before the colposcopy appointment, and the last online questionnaire
      (T3) was completed directly following colposcopy at the out-patient clinic. The
      questionnaires included the Spielberger State-Trait Anxiety Inventory (STAI), the
      Hospital Anxiety and Depression Scale (HADS), and the Numeric Rating Scale (NRS)
      to assess pain. RESULTS: The STAI state anxiety score was high (44.6), but there
      was no significant difference in STAI, HADS and NRS between the two groups at the
      three measuring points. A post hoc analysis showed that women with a generally
      higher baseline anxiety trait had significantly lower HADS anxiety levels
      following video information. CONCLUSIONS: Additional information (video) before
      colposcopy did not significantly reduce anxiety, depression, and expected or
      experienced pain, as measured by the STAI, HADS and NRS in patients attending
      their first colposcopy appointment. However, most patients positively appreciated
      the video information, which may reduce the anxiety of extremely anxious
      patients.

PMID- 28760059
TI  - Optimal risk cut-offs for Down syndrome contingent maternal serum screening.
AB  - OBJECTIVES: The objective of this study is to identify the optimal cut-off points
      of contingent serum screening excluding nuchal translucency (NT) measurement, to
      categorize the risk level in the first trimester. METHODS: A prospective database
      of women undergoing contingent serum screening, without NT measurement, was
      reviewed. In conventional categorization, the results of first-trimester
      screening were categorized into high risk (>1:30) (invasive diagnosis was
      offered); intermediate risk (1:30-1:1500) (second-trimester screening was
      needed); and low risk (<1:1500) (no further test). We recategorized the risk
      levels using various upper and lower cut-offs and compared detection rates, false
      positive rates, and rates of intermediate risk. RESULTS: Among 24,874 women, the
      prevalence of Down syndrome was 1:691. The previously agreed cut-offs had a
      detection rate of 88.9% and a false-positive rate of 8.5% with high rate of
      intermediate risk (38.2%). Re-categorization provided the optimal lower and upper
      cut-offs 1/900 and 1/50, respectively, giving a detection rate of 86.1%, a false
      positive rate of 8.1%, and a rate of intermediate risk of 24.8%. CONCLUSIONS:
      This is the first study on contingent serum screening without NT measurement
      which shows a high detection rate with an acceptable false-positive rate. The
      optimal cut-offs to categorize the risk levels of the upper and the lower cut-off
      was 1:30-1:50 and 1:900, respectively.

PMID- 28760060
TI  - Spontaneous spinal epidural haematoma during pregnancy.

PMID- 28760061
TI  - The interdependence of posttraumatic stress symptoms in parental dyads during and
      after their child's treatment for cancer.
AB  - BACKGROUND: Cancer in a child is highly distressing and some parents are at
      increased risk for developing posttraumatic stress symptoms (PTSS). However, the
      interdependence of PTSS in parental dyads has rarely been accounted for. The aim
      was to explore the dyadic relationship of PTSS in parents of children diagnosed
      with cancer. MATERIAL AND METHODS: The sample includes 150 parents (75 dyads) of
      75 children diagnosed with cancer in Sweden during 2002-2004, with follow-up
      until one year after end of treatment. Data on PTSS from six assessments were
      included. The first three assessments were carried out during treatment and the
      remaining after end of treatment. Actor-partner interdependence models were
      estimated using a structural equation modeling approach to explore the dyadic
      relationship of PTSS. Actor effects refer to intra-individual dependency over
      time, and partner effects refer to inter-individual dependency over time, i.e.,
      how much an individual's symptom levels are affected by their partner's symptom
      levels at the previous assessment. RESULTS: Results show both actor and partner
      effects during the child's treatment. Only an actor effect remained following end
      of treatment where level of PTSS at one assessment was associated with the level
      of PTSS at the subsequent assessment. The association between mothers' and
      fathers' PTSS did not remain after end of treatment. CONCLUSIONS: Parents appear
      to react as an interdependent emotional system during the child's treatment but
      this effect disappears after end of treatment. Results suggest psychological
      interventions for parents during the child's cancer treatment should also be
      sensitive to and address the influence that distress in one partner may have on
      the other.

PMID- 28760062
TI  - High rate of uterine rupture in a conflict setting of Hajjah, Yemen.
AB  - A descriptive study was conducted to investigate the epidemiology and the outcome
      of uterine rupture at Hajjah Hospital, Yemen, during September 2014-August 2016.
      There were 110 cases of ruptured uterus and 3457 deliveries (31.8 per 1000
      delivery). The majority (82, 74.5%) of these patients were illiterate. One
      hundred and four (96.3%) of them had no antenatal care. Seventy-eight of these
      women (70.9%) delivered at home and 32 (29.1%) delivered at hospital. Out of
      these 110 cases, 74 (67.3%) and 36 (32.7%) had unscarred uterus and scarred
      uterus, respectively. The causes of ruptured uterus were as follows: obstructed
      labour 59 (53.6%), previous caesarean delivery 36 (32.7%), use of oxytocin 10
      (9.1%) and misoprostol 5 (4.6%). Hysterectomy was carried out in 50 (45.4%) %),
      repair in 39 (35.4%), repair with tubal ligation in 18 (16.4%) patients and 3
      (2.7%) patients died before operation. There was 8 (7.2%) and 101 (91.8%)
      maternal and perinatal mortality, respectively. Nineteen (17.3%), 6 (5.4%) and 2
      (1.8%) women developed sepsis, had urinary bladder injury and developed
      vesicovaginal fistulae, respectively.

PMID- 28760063
TI  - Incremental economic burden associated with major bleeding among atrial
      fibrillation patients treated with factor Xa inhibitors.
AB  - OBJECTIVE: To evaluate healthcare resource use and costs incurred during, as well
      as following hospitalization for major bleeding (MB), among atrial fibrillation
      (AF) patients treated with factor Xa inhibitors Methods: Patients with an AF
      diagnosis and MB hospitalization (index event) were identified from the
      MarketScan Commercial and Medicare databases (January 1, 2011-December 31, 2014).
      Patients were required to have >=1 prescription for rivaroxaban or apixaban
      within 3 months prior to MB hospitalization. AF patients treated with Xa
      inhibitors, but who did not have any diagnosis of MB during the study period were
      identified. Hospital resource use and costs were evaluated for index MB
      hospitalizations. Healthcare resource use and associated costs were also
      evaluated for up to 12 months and compared between AF patients with and without
      MB. RESULTS: Of the overall patient population with AF treated with factor Xa
      inhibitors (n = 92,949), 3,081 (3.3%) were identified as patients with MB and
      89,868 without MB. The mean hospital length of stay and hospital cost for index
      MB hospitalizations were 5.3 days and $28,059, respectively. Total all-cause
      healthcare costs were higher during the 12 months of follow-up for AF patients
      with MB vs without ($63,866 vs $37,916, p < .001). After adjusting for
      differences in patient characteristics, mean total healthcare costs were
      estimated at $58,169 for patients with MB vs $41,241 for patients without MB.
      LIMITATIONS: Since this was an observational study using a claims database
      analysis, a causal relationship between factor Xa inhibitor treatment and MB
      events cannot be inferred from the results of this study. CONCLUSION: In the real
      world setting, the cost of initial hospitalizations for MB was substantial, and
      the incremental burden of total healthcare costs within 1 year following MB
      hospitalization was high. Approaches to better manage the continuum of care of AF
      patients with factor Xa inhibitor-associated MB may reduce the healthcare
      economic burden.

PMID- 28760065
TI  - Risk of major amputation or death among patients with critical limb ischemia
      initially treated with endovascular intervention, surgical bypass, minor
      amputation, or conservative management.
AB  - AIMS: Patients with critical limb ischemia (CLI) have an increased risk of major
      amputation. The initial treatment approach for CLI may significantly impact the
      subsequent risk of major amputation or death. The objective of this study was to
      describe the initial treatment approaches of patients with CLI and the limb
      outcomes associated with each approach. METHODS: Data from MarketScan Commercial
      and Medicare Supplemental Databases from January 2006-December 2014 was utilized.
      Cohorts of CLI patients were defined as follows: (1) peripheral vascular
      intervention (PVI); (2) peripheral vascular surgery (PVS); (3) minor amputation
      without concomitant PVI or PVS (MinAMP); and (4) Patients without PVI, PVS, or
      MinAMP (conservative therapy). The odds of major amputation or inpatient death
      were estimated using the Cox proportional hazards model. For those patients
      requiring a major amputation, the incremental expenditures per member per month
      (PMPM) were estimated using a gamma log-link model. RESULTS: Conservative therapy
      was associated with significantly higher odds of major amputation or inpatient
      death compared to patients who underwent minor amputation (1.59-times), PVI (2.08
      times), or PVS (2.12-times). Patients treated with an initial strategy of minor
      amputation also had higher odds of major amputation or inpatient death compared
      to PVS (1.31-times) or PVI (1.33-times). The estimated incremental expenditures
      PMPM for patients with a major amputation was $5,165. CONCLUSIONS:
      Revascularization reduces the risk of a major amputation or inpatient death for
      patients with CLI when compared to conservative therapy. Major amputation is also
      associated with significantly higher healthcare expenditures.

PMID- 28760066
TI  - Diabetic ketoacidosis masquerading as pre-eclampsia: a case report.

PMID- 28760067
TI  - A late complication developing 12 years after a transobturator tape procedure:
      vulvar abscess with vaginocutaneous fistula.

PMID- 28760068
TI  - A novel and dedicated multidisciplinary service to manage breech presentation at
      term; 3 years of experience in a tertiary care maternity unit.
AB  - OBJECTIVE: In order to provide uniform and unbiased multidisciplinary counselling
      on the options available, including vaginal breech delivery (VBD) and external
      cephalic version (ECV), the latter of which could then be performed, a weekly
      Breech Clinic was introduced to a tertiary care maternity unit in Northern
      Ireland in June 2013, replacing the traditional ECV Clinic introduced in June
      2012. METHODS: Retrospective data collection was undertaken using clinic
      proformas, Northern Ireland Maternity System data and case notes of women who
      attended the clinics (ECV and Breech) from June 2012 to May 2015. RESULTS: There
      were 434 referrals to the clinic over the 3-year period; 356 women attended. The
      proportion of women attending increased from 69% to 85% since the introduction of
      the Breech Clinic. Two hundred and thirty-two were deemed eligible and 179 of
      these underwent ECV after counselling. Although the proportion of women
      undergoing ECV decreased from 69% to 46%, 11 women opted for and achieved VBD
      during the 2 years of the Breech Clinic, compared with one woman in the year of
      the ECV Clinic. Seventy-one of the attempted ECVs were successful, with 61 women
      having a normal vaginal delivery. Notably, the success rate of ECV increased from
      33% to 42%. The number of caesarean sections performed solely for breech at term
      decreased from 199 in the 12 months before the introduction of ECV clinic, to 188
      during the ECV clinic, and 154 in the final 12 months of Breech Clinic.
      CONCLUSIONS: A dedicated service to counsel women on the management of breech
      presentation can decrease caesarean sections for breech presentation through
      increased uptake and success of ECV, and encouraging suitable women to opt for
      VBD when ECV is unsuccessful, contraindicated or declined.

PMID- 28760069
TI  - The early postnatal blood flow characteristics in the superior mesenteric and
      coeliac arteries in late preterm neonates.
AB  - OBJECTIVES: The objective of this study is to evaluate intestinal blood flow
      changes within the first 72 h in the late preterm infants in comparison with the
      healthy term neonates. METHODS: In this prospective study, we analyzed Doppler
      flow velocity waveforms of superior mesenteric artery (SMA) and coeliac trunc
      (TC) in 20 late preterm and 20 term infants at the age of 2, 24, and 72 h.
      RESULTS: Significant end-diastolic velocity (end-diastolic velocity (EDV)SMA)
      rise up to 24 h was documented in all patients (late preterm: -9.32 +/- 9.48 to
      17.01 +/- 6.94; p < .05; term: -8 +/- 5.74 to 12.39 +/- 3.33; p < .001),
      associated with a conversion from negative values to positive ones. Reversed
      blood flow was documented in SMA at 2 h in 75% late preterm neonates. Preterm
      infants showed significantly higher mean peak systolic velocities (peak systolic
      velocity (PSV)SMA), end-diastolic velocities (EDVSMA) at 24 h and PSVTC at 72 h
      than term infants (p < .05). The resistance and pulsatility indices (PI)
      decreased within 24 h in both groups and inversely reflected the postnatal
      changes in EDVSMA. Mean PIAMS at 2 h was significantly higher in term neonates.
      CONCLUSION: Late preterm neonates show similar progressive postnatal increase in
      blood flow velocities accompanied with a decrease in vascular resistance in SMA
      and TC then term neonates.

PMID- 28760070
TI  - Prevalence and calf-level risk factors for failure of passive transfer in dairy
      calves in New Zealand.
AB  - AIM To determine the prevalence of failure of passive transfer (FPT) in dairy
      calves in New Zealand and to assess a range of potential calf-level risk factors
      for their association with FPT. METHOD Between July and September 2015, 107 dairy
      farms in nine regions across New Zealand were visited on three occasions: before
      20% of cows had calved, when ~50% of cows had calved, and when the last 10-20% of
      cows were calving. Farms were randomly selected from the client list of
      participating veterinary practices. On each farm, blood samples were collected
      from 10-20 calves between 24 hours and 8 days old and concentrations of total
      protein (TP) in serum determined. Calf identification, date of birth, dam's age
      and breed, details of colostrum feeding and the farmer's health assessment of the
      calf on arrival at the calf rearing facility were recorded. Concentrations of TP
      in serum <=52 g/L were used to define FPT. RESULTS Of 3,819 calves sampled, 1,263
      (33 (95% CI=31.6-34.6)%) were diagnosed with FPT, and the prevalence within farms
      ranged from 5-83%. Calf-level risk factors that were associated with increased
      odds of FPT were increasing age of dam (OR=1.12; 95% CI=1.08-1.16), calves
      recorded as unhealthy compared to healthy upon arrival at the calf rearing
      facility (OR=2.59; 95% CI=1.60-4.19), calves sampled on farms in Otago (OR=2.85;
      95% CI=1.42-5.74) and Southland (OR 2.31; 95% CI=1.15-4.67) compared to the Far
      North, and calves sampled in the middle compared to the early calving period
      (OR=1.24; 95% CI=1.03-1.51). CONCLUSION On the farms visited FPT was diagnosed in
      one third of dairy calves. Calf-level risk factors for FPT included age of dam,
      health status of calf, region, and time of the calving period. Further
      investigations are required to establish why these are associated with increased
      odds of FPT. CLINICAL RELEVANCE These results provide a baseline for
      benchmarking, which, alongside the reported calf-level risk factors, can be used
      by veterinarians to improve colostrum management.

PMID- 28760071
TI  - Do 'blacheap' and 'subcheap' both prime 'cheap'? An investigation of morphemic
      status and position in early visual word processing.
AB  - Much research suggests that words comprising more than one morpheme are
      decomposed into morphemes in the early stages of visual word recognition. In the
      present masked primed lexical decision study, we investigated whether or not
      decomposition occurs for both prefixed and suffixed nonwords and for nonwords
      which comprise a stem and a non-morphemic ending. Prime-target relatedness was
      manipulated in three ways: (1) primes shared a semantically transparent
      morphological relationship with the target (e.g., subcheap-CHEAP, cheapize
      CHEAP); (2) primes comprised targets and non-affixal letter strings (e.g.,
      blacheap-CHEAP, cheapstry-CHEAP); and (3) primes were real, complex words
      unrelated to the target (e.g., miscall-CHEAP, idealism-CHEAP). Both affixed and
      non-affixed nonwords significantly facilitated the recognition of their stem
      targets, suggesting that embedded stems are activated independently of whether
      they are accompanied by a real affix or a non-affix. There was no difference in
      priming between stems being embedded in initial and final string positions,
      indicating that embedded stem activation is position-independent. Finally, more
      priming was observed in the semantically interpretable affixed condition than in
      the non-affixed condition, which points to a semantic licensing mechanism during
      complex novel word processing.

PMID- 28760072
TI  - Omega-3 fatty acid attenuates oxidative stress in cerebral cortex, cerebellum,
      and hippocampus tissue and improves neurobehavioral activity in chronic lead
      induced neurotoxicity.
AB  - OBJECTIVES: In view of the increasing risk of lead on human health, the present
      study has been carried out to investigate the neuroprotective effect of omega-3
      fatty acid on chronic lead-induced neurotoxicity and behavioral impairment in
      rats. METHODS: Different neurobehavioral parameters, biochemical assays, and
      histopathological analyses in brain regions of rats were conducted. RESULTS: Rats
      exposed to different doses of lead (lead acetate 2.5, 5.0, 7.5 mg/kg body weight
      p.o. for 90 days) caused a significant decrease in body weight, brain weight, and
      behavioral changes as compared to controls. Abnormal histopathological and
      increased levels of lead in blood and brain regions increased the levels of ROS,
      LPO, PCC and decreased the levels of GSH with concomitant reduction in SOD, CAT,
      and GPx activities in the brain region of rats treated with different doses of
      lead as compared to controls. Co-treatment of lead with omega-3 fatty acid (500
      mg/kg body weight p.o. for 90 days) decreased the levels of ROS, LPO, PCC, and
      increased the level of GSH, also increased SOD, CAT, and GPx activity and showed
      improvements in behavioral as well as histopathological changes as compared to
      lead-treated groups. DISCUSSION: Our results proved that omega-3 fatty acid
      improved behavioral deficits, altered histopathological and oxidative stress in
      lead-intoxicated rats. Among three different doses, 2.5 mg/kg b.wt. of lead along
      with omega-3 fatty acid was the most preventive dose for the neurotoxicity. This
      work reveals the potential of omega-fatty acid as a protective drug for lead
      neurotoxicity.

PMID- 28760073
TI  - Understanding TMJ reactive arthritis.

PMID- 28760074
TI  - Redox status on different regions of the central nervous system of obese and lean
      rats treated with green tea extract.
AB  - OBJECTIVES: The purpose of this study was to evaluate some indicators of redox
      status, and inflammation on different regions of the central nervous system (CNS)
      of obese rats treated with green tea (GT). We hypothesized that obesity could
      affect the redox balance in different brain regions due to the diverse nature of
      the cells as well as the selective neuronal vulnerability to oxidative stress,
      and GT could triggers benefits effects restoring the redox status. METHODS: Male
      Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of
      body weight) and obesity was induced by cafeteria diet (8 weeks). After this
      period, the animals were killed and brain tissue (cerebral cortex, cerebellum,
      and brainstem) was removed to evaluate oxidative stress and inflammation
      (cytokine release). RESULTS: We showed that the cafeteria diet had little effect
      on redox balance in the cerebral cortex and cerebellum; however, the brainstem
      was the region of the CNS most sensitive to cafeteria diet-induced redox
      unbalance. GFAP expression was increased in the cerebral cortex of obese rats and
      reduced by GT. It was also evident that GT treatment had numerous beneficial
      effects against oxidative damage to biomolecules in all brain regions analyzed.
      DISCUSSION: Our study established that different CNS regions show selective
      neuronal vulnerability when exposed to a diet enriched with fats and sugars, and
      the beneficial effect of GT was similar among these regions. We conclude that GT
      could be a good strategy for improving and maintaining brain function under
      healthy and pathological conditions.

PMID- 28760075
TI  - Meta-analysis of rare binary events in treatment groups with unequal variability.
AB  - Meta-analysis has been widely used to synthesize information from related studies
      to achieve reliable findings. However, in studies of rare events, the event
      counts are often low or even zero, and so standard meta-analysis methods such as
      fixed-effect models with continuity correction may cause substantial bias in
      estimation. Recently, Bhaumik et al. developed a simple average estimator for the
      overall treatment effect based on a random effects model. They proved that the
      simple average method with the continuity correction factor 0.5 (SA_0.5) is the
      least biased for large samples and showed via simulation that it has superior
      performance when compared with other commonly used estimators. However, the
      random effects models used in previous work are restrictive because they all
      assume that the variability in the treatment group is equal to or always greater
      than that in the control group. Under a general framework that explicitly allows
      treatment groups with unequal variability but assumes no direction, we prove that
      SA_0.5 is still the least biased for large samples. Meanwhile, to account for a
      trade-off between the bias and variance in estimation, we consider the mean
      squared error to assess estimation efficiency and show that SA_0.5 fails to
      minimize the mean squared error. Under a new random effects model that
      accommodates groups with unequal variability, we thoroughly compare the
      performance of various methods for both large and small samples via simulation
      and draw conclusions about when to use which method in terms of bias, mean
      squared error, type I error, and confidence interval coverage. A data example of
      rosiglitazone meta-analysis is used to provide further comparison.

PMID- 28760076
TI  - Saccades and smooth pursuit eye movements trigger equivalent gaze-cued orienting
      effects.
AB  - Research has established that a perceived eye gaze produces a concomitant shift
      in a viewer's spatial attention in the direction of that gaze. The two
      experiments reported here investigate the extent to which the nature of the eye
      movement made by the gazer contributes to this orienting effect. On each trial in
      these experiments, participants were asked to make a speeded response to a target
      that could appear in a location toward which a centrally presented face had just
      gazed (a cued target) or in a location that was not the recipient of a gaze (an
      uncued target). The gaze cues consisted of either fast saccadic eye movements or
      slower smooth pursuit movements. Cued targets were responded to faster than
      uncued targets, and this gaze-cued orienting effect was found to be equivalent
      for each type of gaze shift both when the gazes were un-predictive of target
      location (Experiment 1) and counterpredictive of target location (Experiment 2).
      The results offer no support for the hypothesis that motion speed modulates gaze
      cued orienting. However, they do suggest that motion of the eyes per se,
      regardless of the type of movement, may be sufficient to trigger an orienting
      effect.

PMID- 28760077
TI  - Mothers' experiences of coping with adolescent substance abuse: a
      phenomenological inquiry.
AB  - BACKGROUND AND STUDY AIM: Adolescent substance abuse significantly impacts on the
      lives of mothers. This paper explores the coping responses of mothers whose
      adolescents have been admitted to treatment for substance abuse. DESIGN AND
      METHOD: A multiple case study design was adopted and the data were collected
      through one-on-one interviews facilitated by the Lifegrid. Interpretative
      phenomenological analysis was used to interrogate the data. RESULTS: Coping
      emerged as a complex construct in our analysis. The mothers' used problem-focused
      and emotion-focused coping in different combinations of withdrawing, tolerating
      and engaged coping responses. The mothers' coping responses were also influenced
      by individual and relational factors like subjective distress and the mother
      adolescent relationship. CONCLUSIONS: We argue that research and practice
      initiatives should consider using a multidimensional perspective of parental
      coping that recognises the heterogeneity of mothers' coping responses. Impact
      statement: The current paper offers new insights into the complexities of
      mothers' coping responses to adolescent substance abuse.

PMID- 28760078
TI  - Erratum.

PMID- 28760079
TI  - Preparation of cell aggregates incorporating gelatin hydrogel microspheres
      containing bone morphogenic protein-2 with different degradabilities.
AB  - The objective of this study is to evaluate the survival and functions of cells in
      cell aggregates incorporating gelatin hydrogel microspheres (GM) containing bone
      morphogenic protein-2 (BMP2). Gelatin was dehydrothermally crosslinked in a water
      in-oil emulsion state at 140  degrees C for various time periods to prepare GM
      with different degradabilities. BMP2 was dropped onto the GM freeze dried,
      followed by leaving at 25  degrees C to obtain GM containing BMP2 (GM-BMP2).
      MC3T3-E1 cells were cultured with GM-BMP2 and GM in round U-bottom wells of 96
      multiwell microplates which had been coated with poly (vinyl alcohol) (PVA), to
      allow to form cell aggregates containing GM-BMP2 and GM, respectively. Higher
      MC3T3-E1 cell proliferation and the L-lactic acid/glucose ratio were observed for
      MC3T3-E1 cell aggregates cultured with the GM of slower degradation. The runt
      related transcription factor 2 (RUNX2) messenger ribonucleic acid (mRNA)
      expression, alkaline phosphatase (ALP) activity, and calcium content of MC3T3-E1
      cells in cell aggregates were assayed to evaluate their osteogenic
      differentiation. When cultured for 7 days with GM-BMP2 or free BMP2, the RUNX2
      mRNA expression and ALP activity were higher for MC3T3-E1 cell aggregates
      cultured with the GM-BMP2 of faster degradation than those of free BMP2 added
      into the medium. After 21 days culture, the ALP activity and calcium content were
      higher for the GM-BMP2 of medium degradation compared with other experimental
      groups. It is concluded that BMP2 of GM-BMP2 incorporated in the cell aggregates
      enhanced the osteogenic differentiation of cells compared with free BMP2 added
      externally. The degradability of GM-BMP2 affected the extent of osteogenic
      differentiation.

PMID- 28760080
TI  - A comparison of breastfeeding rates by obesity class.
AB  - PURPOSE: The purpose of this study is to compare breastfeeding initiation rates
      for women across body mass index (BMI) classes, including normal BMI (18.50-24.99
      kg/m2), overweight (25.00-29.99 kg/m2), obese (30.00-39.99 kg/m2), morbidly obese
      (40.00-49.99 kg/m2) and extreme obesity (>=50.00 kg/m2). MATERIALS AND METHODS:
      Retrospective cohort of women with singleton pregnancies, delivering in St.
      John's, NL between 2002 and 2011. The primary outcome was any breastfeeding on
      hospital discharge. Breastfeeding rates across BMI categories were compared,
      using univariate analyses. Multivariate analysis included additional maternal and
      obstetric variables. RESULTS: Twelve thousand four hundred twenty-two women were
      included: 8430 breastfed and 3992 did not breastfeed on hospital discharge.
      Progressively decreasing rates of breastfeeding were noted with increasing
      obesity class: normal BMI (71.1%), overweight (69.1%), obese (61.6%), morbidly
      obese (54.2%), and extremely obese women (42.3%). Multivariate analysis confirmed
      that increasing obesity class resulted in lower odds of breastfeeding: overweight
      (adjusted odds ratios (aOR) 0.86, 95%CI 0.76-0.98), obese (aOR 0.65, 95%CI 0.57
      0.74), morbidly obese (aOR 0.57, 95%CI 0.44-0.74), and extreme obesity (aOR 0.37,
      95%CI 0.19-0.74). CONCLUSION: Women in higher obesity classes are progressively
      less likely to initiate breastfeeding. Women with the highest prepregnancy BMIs
      should be particularly counseled on the benefits of breastfeeding.

PMID- 28760081
TI  - Plasma concentrations of ascorbic acid in a cross section of the German
      population.
AB  - Objectives Vitamin C deficiency is considered extremely rare in modern
      industrialized countries. This study was performed to assess vitamin C
      concentrations in the German population. Methods As part of a consultant-patient
      seminar on nutrition and food intolerances, patients were asked to participate in
      this study on a voluntary basis. Blood samples were taken for analysis of serum
      vitamin C concentrations, and all patients were asked to complete a
      questionnaire. The vitamin C concentration was determined by high-performance
      liquid chromatography. Results Of approximately 300 patients attending the
      seminar, 188 (62.6%) consented to vitamin C blood sample analysis and 178 (59.3%)
      answered the questionnaire. The mean vitamin C concentration was 7.98 mg/L
      (range, 0.50-17.40; reference range, 5-15 mg/L). A low plasma level with vitamin
      C insufficiency (<5 mg/L) was found in 31 patients (17.4%), and a potential
      scorbutogenic deficiency (<1.5 mg/L) was found in 6 (3.3%). Conclusions Potential
      vitamin C insufficiency and deficiency is common. It is therefore possible, even
      in modern developed populations, that certain individuals may require a higher
      intake of vitamin C.

PMID- 28760082
TI  - Mycoplasma pneumoniae 23S rRNA A2063G mutation does not influence chest
      radiography features in children with pneumonia.
AB  - Objective To measure the rate of the A2063G mutation in the Mycoplasma pneumoniae
      ( M. pneumoniae) 23S rRNA domain V in children with pneumonia and to determine
      the correlation between radiographic findings and the presence of the A2063G
      mutation. Methods Patients who were hospitalized with a confirmed diagnosis of M.
      pneumoniae pneumonia were enrolled in this study. M. pneumoniae strains were
      collected for genotype analysis. Chest radiography was performed on all children
      prior to and following macrolide treatment. Clinical and imaging data were
      obtained. Results Of 211 patients, 195 (92.42%) harboured M. pneumoniae with the
      A2063G mutation. No significant differences were identified in inflammation
      score, chest radiography inflammation absorption grade before and after macrolide
      treatment, or pulmonary complications (atelectasis, hydrothorax, or pleuritis)
      prior to macrolide treatment when children were stratified based on the presence
      or absence of the A2063G mutation. Conclusions A high proportion of children with
      pneumonia harboured strains of M. pneumoniae with the A2063G mutation in the 23S
      rRNA domain V. However, no obvious chest radiographic features of M. pneumoniae
      pneumonia were associated with the A2063G variant.

PMID- 28760083
TI  - Understanding ageing: fear of chronic diseases later in life.
AB  - Objectives Ageing is often associated with deteriorating mental and physical
      health and the need for long-term care, creating a fear of ageing. We
      investigated what people fear most in terms of disabling chronic diseases and
      their concerns regarding having long-term illnesses. Methods Data were obtained
      from an online survey of 518 respondents aged 40 years and older residing in
      Malaysia, which was based on a convenience sample collected in May 2015 to
      January 2016. Data were analyzed using chi-squared tests and multinomial logistic
      regression. Results Of the most dreaded diseases, heart disease and cancer are
      life-threatening; however, dementia, diabetes, and hypertension persist and have
      a disabling effect for a long time. While there were variations in the diseases
      feared most across sex, ethnicity, and place of residence, the biggest worry for
      all respondents with regard to having a long-term illness was that they would
      become a burden to their family, a concern that superseded fear of dying.
      Conclusions We found our survey respondents had a fear of chronic diseases and
      placing a burden on others. Thus, there is a need to provide motivation for
      people to adopt a healthy lifestyle, to remain healthy.

PMID- 28760084
TI  - Optimal dilution of contrast medium for quantitating parenchymal blood volume
      using a flat-panel detector.
AB  - Objective Similar to perfusion studies after acute ischemic stroke, measuring
      cerebral blood volume (CBV) via C-arm computed tomography before and after
      therapeutic interventions may help gauge subsequent revascularization. We tested
      serial dilutions of intra-arterial injectable contrast medium (CM) to determine
      the optimal CM concentration for quantifying parenchymal blood volume by flat
      panel detector imaging (FD-PBV). Methods CM was diluted via saline power
      injector, instituting time delays for FD-PBV studies. A red/green/blue (RGB)
      color scale was employed to quantify/compare FD-PBV and magnetic resonance
      derived CBV (MRCBV). Results Contrast values of right and left common carotid
      arteries did not differ significantly at CM dilutions of >=20%. RGB analysis of
      FD-PBV imaging (relative to MR-CVB), showed CM dilution altered the colors (by
      16%), increasing red and decreasing blue ratios. Conclusion Diluting CM to 20%
      resulted in no laterality differential of FD-PBV imaging, with left/right
      quantitative ratios approaching 1.1 (optimal for clinical use).

PMID- 28760085
TI  - The impact of RAGE inhibition in animal models of bacterial sepsis: a systematic
      review and meta-analysis.
AB  - Objective To evaluate the impact of inhibition of the receptor for advanced
      glycation end products (RAGE) on the outcome of bacterial sepsis in animal
      models. Methods Relevant publications were identified by systematic searches of
      PubMed, ISI Web of Science and Elsevier-Scopus databases. Results A total of
      Eleven studies with moderate quality were selected for analysis. A meta-analysis
      of survival rates revealed a significant advantage of RAGE inhibition in
      comparison with controls (HR 0.67, 95% CI 0.52-0.86). This effect was most
      pronounced in polymicrobial infection (HR 0.28, 95% CI 0.14-0.55), followed by
      Gram positive (G+) bacterial infection (HR 0.70, 95% CI 0.50-0.97) and Gram
      negative (G-) bacterial infection (HR 0.89, 95% CI 0.58-1.38). For G+ bacterial
      infection, RAGE inhibition decreased bacterial outgrowth and dissemination,
      inflammatory cell influx, plasma cytokine levels, and pulmonary injury.
      Conclusions RAGE inhibition appears to have a beneficial impact on the outcome of
      sepsis in animal models, although there are discrepancies between different types
      of infection.

PMID- 28760086
TI  - Finite element analysis of locking plate and 1/4 tubular plate for first
      tarsometatarsal joint fracture-dislocation.
AB  - Objective The optimal plate for fixation of tarsometatarsal joint injuries is
      controversial. The objective of this study was to compare the biomechanical
      characteristics between a locking plate and 1/4 tubular plate for first
      tarsometatarsal joint fracture-dislocation. Method Finite element analysis was
      used after establishment of a first tarsometatarsal joint fracture-dislocation
      model. Two implant simulations using a locking plate and five-hole 1/4 tubular
      plate were designed to simulate fixation of the fracture-dislocation. The
      displacement of the first tarsometatarsal articular surface and the stress
      distribution in the implants were calculated. Results A 700-N load was applied to
      both models. The minimum displacement of the articular surface in the locking
      plate and 1/4 tubular plate model was 0.6471 mm and 0.3833 mm, respectively. The
      maximum principal stress in the locking plate and 1/4 tubular plate was 1.212 *
      103  MPa and 1.107 * 103  MPa, respectively. Conclusion Use of a 1/4 tubular
      plate is recommended for fixation of first tarsometatarsal joint fracture
      dislocation after consideration of other factors such as economical issues.

PMID- 28760088
TI  - Race and Victim Age Matter: Sexual Behaviors and Experiences Among Confined
      African American and European American Youth With Sexual and Nonsexual Offenses.
AB  - Previous research has found differences in sexual behavior and types of sexual
      offending by offense category and racial/ethnic group. The present study examined
      effects of offense category, victim age, and race/ethnicity on sexual behavior.
      Data from 561 confined adolescents adjudicated for illegal sexual behavior
      (AISBs) and adolescents adjudicated for illegal nonsexual behavior (AINBs) were
      included in the present study. A hierarchical multinomial logistic regression was
      run to test whether sexual experiences and behaviors differentially predicted
      AINBs, AISBs with child victims, and AISBs with peer/adult victims. Results
      supported the utility of distinguishing AISBs by victim age. Comparisons between
      AISBs and AINBs indicated AISBs had more sexual abuse and were more sexually
      restricted, whereas AINBs reported more sexual behavior, reflecting a finding
      potentially mirroring sexual development, sexual experiences, and caregiver
      approaches to discussing sexuality. Over 60% of AINBs and 30% of AISBs reported
      behaviors that could be classified as distribution of child pornography. Within
      the group of AISBs, select racial/ethnic group differences emerged such that
      European American participants were more likely to have had intrafamilial sexual
      experiences and were far less likely to have had vaginal intercourse than African
      American AISBs. Future directions and implications regarding policies related to
      sexual education and sexting are discussed.

PMID- 28760087
TI  - Diabetes Mellitus induces alterations in metallothionein protein expression and
      metal levels in the testis and liver.
AB  - Objective To investigate the effect of diabetes with and without vitamin E
      treatment on testicular metallothionein (MT) and metal (zinc, copper and iron)
      changes. Methods Diabetes was induced with a single intraperitoneal injection
      (i.p.) of streptozotocin in rats, and diabetic rats were given Vitamin E by i.p.
      every other day for 4 weeks. MT protein was measured by the cadmium-haeme assay
      and metal levels were detected by an atomic absorption spectrophotometer. Results
      Diabetes did not change testicular MT protein, but significantly increased
      hepatic MT protein. Diabetes significantly decreased testicular copper, but not
      hepatic copper. Zinc and iron levels were unchanged in both diabetic testis and
      liver. Vitamin E significantly enhanced both testicular and hepatic MT, and zinc
      levels in diabetic rats. Vitamin E slightly decreased the copper levels, but did
      not change the testicular and hepatic iron in diabetic rats. Conclusions
      Testicular MT protein expression was not increased, even though hepatic MT
      significantly increased independent of metal changes, in diabetic rats. Vitamin E
      enhanced testicular and hepatic MT, which correlated with increased zinc levels.

PMID- 28760089
TI  - Feasibility of proton pencil beam scanning treatment of free-breathing lung
      cancer patients.
AB  - BACKGROUND: The interplay effect might degrade the dose of pencil beam scanning
      proton therapy to a degree that free-breathing treatment might be impossible
      without further motion mitigation techniques, which complicate and prolong the
      treatment. We assessed whether treatment of free-breathing patients without
      motion mitigation is feasible. MATERIAL AND METHODS: For 40 lung cancer patients,
      4DCT datasets and individual breathing patterns were used to simulate 4D dynamic
      dose distributions of 3D treatment plans over 33 fractions delivered with an IBA
      universal nozzle. Evaluation was done by assessing under- and overdosage in the
      target structure using the parameters V90, V95, V98, D98, D2, V107 and V110. The
      impact of using beam-specific target volumes and the impact of changes in motion
      and patient anatomy in control 4DCTs were assessed. RESULTS: Almost half of the
      patients had tumour motion amplitudes of less than 5 mm. Under- and overdosage
      was significantly smaller for patients with tumour motion below 5 mm compared to
      patients with larger motion (2% vs. 13% average absolute reduction of V95, 2% vs.
      8% average increase in V107, p < .01). Simulating a 33-fraction treatment, the
      dose degradation was reduced but persisted for patients with tumour motion above
      5 mm (average DeltaV95 of <1% vs. 3%, p < .01). Beam-specific target volumes
      reduced the dose degradation in a fractionated treatment, but were more relevant
      for large motion. Repeated 4DCT revealed that changes in tumour motion during
      treatment might result in unexpected large dose degradations. CONCLUSION: Tumour
      motion amplitude is an indicator of dose degradation caused by the interplay
      effect. Fractionation reduces the dose degradation allowing the unmitigated
      treatment of patients with small tumour motions of less than 5 mm. The beam
      specific target approach improves the dose coverage. The tumour motion and
      position needs to be assessed during treatment for all patients, to quickly react
      to possible changes, which might require treatment adaptation.

PMID- 28760090
TI  - The Impact of Emotional Lability Symptoms During Childhood in Adults With ADHD.
AB  - OBJECTIVE: To determine whether emotional lability (EL) in adult ADHD patients
      can already be identified during their childhood and the extent to which this
      childhood symptomatology can predict EL in adulthood. METHOD: Seven hundred
      eighteen adults with ADHD were examined. EL in adulthood was assessed using the
      Conners' Adult ADHD Rating Scales (CAARS). According to Conners' definition of
      EL, seven items from the Wender Utah Rating Scale (WURS) were used to determine
      this symptomatology in childhood. RESULTS: EL was identified in 31.1% of the
      participants, and 29.6% of this subgroup reported EL symptoms in childhood.
      Childhood EL was the strongest predictor of these symptoms in adulthood (odds
      ratio [OR] = 6.18). ADHD subtype, female sex, family history of ADHD, psychiatric
      comorbidities, and physical abuse were also related to EL
      development/persistence. CONCLUSION: Screening for EL symptoms in children with
      ADHD is important, as they are the strongest predictor of this symptomatology in
      adulthood.

PMID- 28760091
TI  - Pectoralis Major Rupture.
AB  - A 33-year-old male military service member was referred to physical therapy 4
      days after competing in a bench-press competition, during which he was unable to
      accomplish an attempt due to a sharp/stabbing pain in his right shoulder. Given
      the concern for a ruptured pectoralis major, and after consultation with the
      orthopaedic surgeon and radiologist, magnetic resonance imaging was performed.
      Findings revealed a complete rupture of the pectoralis major tendon, with up to 5
      cm of retraction. J Orthop Sports Phys Ther 2017;47(8):578.
      doi:10.2519/jospt.2017.7277.

PMID- 28760092
TI  - When Chronic Pain Is Not "Chronic Pain": Lessons From 3 Decades of Pain.
AB  - The current move in physical therapy toward the biopsychosocial management of
      chronic pain has led some interpreters to call for a less hands-on approach, as
      awareness of central sensitization leads to specific management trends and a move
      away from pathoanatomical considerations. The authors of this Viewpoint suggest
      that no approach, no matter how vocal and evangelistic its followers, would
      likely be any more certain than what preceded it. This Viewpoint poses the
      question, why, when we (as a profession) appear (according to the new physical
      therapy gurus) to have been so wrong before, do we appear to believe that we are
      right this time? J Orthop Sports Phys Ther 2017;47(8):515-517.
      doi:10.2519/jospt.2017.0606.

PMID- 28760093
TI  - Fracture of the Lateral Process of the Talus.
AB  - A 24-year-old woman fell while ice climbing and landed on her left foot.
      Radiographs were taken and read as noncontributory. Eight days after the injury,
      the patient was still unable to bear weight due to significant pain, so she self
      referred to physical therapy. Following evaluation, she was referred to primary
      care for further imaging to rule out fracture. The physician ordered magnetic
      resonance imaging, which revealed a left mildly displaced fracture of the intra
      articular lateral process of the talus. J Orthop Sports Phys Ther 2017;47(8):579.
      doi:10.2519/jospt.2017.7424.

PMID- 28760094
TI  - August 2017 Letters to the Editor-in-Chief.
AB  - Letter to the Editor-in-Chief of JOSPT as follows: "Manual Therapy: More Than
      Elaborate Swordplay" with Authors' Response "Comparing Dry Needling to
      Corticosteroid Injection for Greater Trochanteric Pain Syndrome" with Authors'
      Response J Orthop Sports Phys Ther 2017;47(8):580-585.
      doi:10.2519/jospt.2017.0204.

PMID- 28760095
TI  - SSI/SSDI Outreach, Access, and Recovery (SOAR): Disability Application Outcomes
      Among Homeless Adults.
AB  - OBJECTIVE: The SSI/SSDI Outreach, Access, and Recovery (SOAR) program has been
      shown to increase access to Supplemental Security Income and Social Security
      Disability Insurance benefits among homeless adults. However, little empirical
      data exist on how or for whom SOAR achieves successful application outcomes. This
      study investigated applicant and application characteristics associated with
      disability application outcomes among homeless adults. METHODS: Secondary data on
      6,361 SOAR-assisted applications were obtained. Multilevel models investigated
      between-applicant differences in application processing time and decision as a
      function of applicant and application characteristics. RESULTS: Older age and
      living in an institution were associated with greater odds of application
      approval. Female gender and receipt of public assistance were associated with
      longer processing time and lower odds of approval. Except for quality review,
      SOAR critical components were associated with greater odds of approval.
      CONCLUSIONS: Women and adults receiving public assistance appear disadvantaged in
      the SOAR application process. SOAR critical components promote successful
      disability application outcomes.

PMID- 28760096
TI  - Collaborative Care for Mental Health in Low- and Middle-Income Countries: A WHO
      Health Systems Framework Assessment of Three Programs.
AB  - The collaborative care model is an evidence-based intervention for behavioral and
      other chronic conditions that has the potential to address the large burden of
      mental illness globally. Using the World Health Organization Health Systems
      Framework, the authors present challenges in implementing this model in low- and
      middle-income countries (LMICs) and discuss strategies to address these
      challenges based on experiences with three large-scale programs: an
      implementation research study in a district-level government hospital in rural
      Nepal, one clinical trial in 50 primary health centers in rural India, and one
      study in four diabetes clinics in India. Several strategies can be utilized to
      address implementation challenges and enhance scalability in LMICs, including
      mobilizing community resources, engaging in advocacy, and strengthening the
      overall health care delivery system.

PMID- 28760097
TI  - Adherence to Antipsychotic Therapy: Association With Hospitalization and Medicare
      Spending Among Part D Enrollees With Schizophrenia.
AB  - OBJECTIVE: This study examined relationships among antipsychotic adherence,
      hospitalization, and hospital expenditures in a sample of 13,861 Medicare Part D
      enrollees with schizophrenia. METHODS: Utilization and expenditure data were
      obtained from the Centers for Medicare and Medicaid Services Chronic Conditions
      Warehouse for 2011 and 2012. Adherence was measured with the proportion of days
      covered and stratified into four categories. Probit regressions and two-part
      generalized linear models were used to examine relationships between adherence in
      year 1 and outcomes in year 2. RESULTS: Adherence to antipsychotic therapy was
      associated with a significantly lower probability of psychiatric hospitalization
      and significantly lower psychiatric hospital expenditures, with the largest
      effect sizes observed for the most highly adherent beneficiaries. There was no
      relationship between antipsychotic adherence and hospitalizations or expenditures
      for nonpsychiatric conditions. CONCLUSIONS: Adherence to antipsychotics among
      Medicare Part D enrollees with schizophrenia was associated with significantly
      lower probability of psychiatric hospitalization and lower hospital expenditures.

PMID- 28760099
TI  - The Utility of Outpatient Commitment: II. Mortality Risk and Protecting Health,
      Safety, and Quality of Life.
AB  - OBJECTIVE: This study assessed the contribution of a form of outpatient
      commitment-community treatment orders (CTOs)-to mortality risk and quality of
      life of patients with severe mental illness. METHODS: Data (2000--2012) were
      obtained from the Australian National Death Index, Victoria Department of Health,
      Victoria police records, and National Outcomes and CaseMix Collection quality-of
      life records for patients in the Victorian Psychiatric Case Register/RAPID with a
      history of psychiatric hospitalization: CTO cohort, N=11,424; non-CTO cohort,
      N=16,161. The contribution of CTOs to mortality risk associated with CTO
      facilitation of access to general medical care and prevention of criminal
      involvement was assessed with logistic regression models. Cohort differences in
      quality of life were also examined. RESULTS: A total of 2,727 patients (10%) in
      the overall sample died, and the sample had a higher mortality risk than the
      general population. Probability of death by any cause was 9% lower in the CTO
      cohort than in the non-CTO cohort. Facilitation of access to medical care
      accounted for a 20% reduction in risk of non-injury-related deaths in the CTO
      cohort, compared with the non-CTO cohort. Risk of death by self-harm was 32%
      higher, compared with the non-CTO cohort. CTO placement appeared to lead to a
      gain of 3.8 years of life among men and 2.4 years among women, compared with the
      non-CTO cohort. Quality-of-life scores were modestly less favorable for the non
      CTO cohort. CONCLUSIONS: CTO placement was associated with lower mortality risk
      via facilitated access to medical care and with modest enhancement of quality of
      life.

PMID- 28760098
TI  - Mind the Gap: Developing an Integrated Behavioral Health Home to Address Health
      Disparities in Serious Mental Illness.
AB  - OBJECTIVE: This study evaluated the impact of an integrated behavioral health
      home (BHH) pilot on adults with psychotic and bipolar disorders. METHODS: Quasi
      experimental methods were used to compare outcomes before (September 2014-August
      2015) and after the intervention (September 2015-August 2016) among ambulatory
      BHH patients and a control group. Electronic health records were compared between
      424 BHH patients (N=369, psychotic disorder; N=55, bipolar disorder) and 1,521
      individuals from the same urban, safety-net health system who were not enrolled
      in the BHH. Groups were weighted by propensity score on the basis of sex, age,
      race-ethnicity, language, 2010 U.S. Census block group characteristics, Medicare
      and Medicaid enrollment, and diabetes diagnosis. RESULTS: BHH patients had fewer
      total psychiatric hospitalizations and fewer total emergency visits compared with
      the control group, a difference that was predominantly driven by patients with at
      least one psychiatric hospitalization or ED visit. There were no differences in
      medical hospitalizations. Although BHH patients were more likely to receive HbA1c
      screening, there were no differences between the groups in lipid monitoring.
      Regarding secondary outcomes, there were no significant differences in changes in
      metabolic monitoring parameters among patients with diabetes. CONCLUSIONS:
      Participation in a pilot ambulatory BHH program among patients with psychotic and
      bipolar disorders was associated with significant reductions in ED visits and
      psychiatric hospitalizations and increased HbA1c monitoring. This evaluation
      builds on prior research by specifying intervention details and the clinical
      target population, strengthening the evidence base for care integration to
      support further program dissemination.

PMID- 28760100
TI  - The Utility of Outpatient Commitment: I. A Need for Treatment and a Least
      Restrictive Alternative to Psychiatric Hospitalization.
AB  - OBJECTIVES: This study examined whether psychiatric patients assigned to
      community treatment orders (CTOs), outpatient commitment in Victoria, Australia,
      have a greater need for treatment to protect their health and safety than
      patients not assigned to CTOs. It also considered whether such treatment is
      provided in a least restrictive manner-that is, in a way that contributes to
      reduced use of psychiatric hospitalization. METHODS: The sample included 11,424
      patients first placed on a CTO between 2000 and 2010, and 16,161 patients not
      placed on a CTO. Need for treatment was independently assessed with the Health of
      the Nation Outcome Scales (HoNOS) at hospital admission and at discharge.
      Ordinary least-squares and Poisson regressions were used to assess savings in
      hospital days attributable to CTO placement. RESULTS: HoNOS ratings indicated
      that at admission and discharge, the CTO cohort's need for treatment exceeded
      that of the non-CTO cohort, particularly in areas indicating potential dangerous
      behavior. When analyses adjusted for the propensity to be selected into the CTO
      cohort and other factors, the mean duration of an inpatient episode was 4.6 days
      shorter for the CTO cohort than for the non-CTO cohort, and a reduction of 10.4
      days per inpatient episode was attributable to each CTO placement. CONCLUSIONS:
      CTO placement may have helped patients with a greater need for treatment to
      experience shorter hospital stays. Whether the CTO directly enabled the
      fulfillment of unsought but required treatment needs that protected patient
      health and safety is a question that needs to be addressed in future research.

PMID- 28760101
TI  - Follow-Up After Discharge From an Inpatient Psychiatric Facility.

PMID- 28760102
TI  - Exacerbation of Psychiatric Symptoms of Undocumented Immigrant Patients Under a
      New Administration.

PMID- 28760104
TI  - New Directions for Promoting Service Engagement.

PMID- 28760103
TI  - Trajectory of PTSD Symptom Change in the Course of Exposure Therapy Among
      Veterans With Severe Mental Illness.

PMID- 28760105
TI  - A Raisin Brings the Sun.

PMID- 28760106
TI  - An Automated Text-Messaging System to Monitor Emotional Recovery After Pediatric
      Injury: Pilot Feasibility Study.

PMID- 28760107
TI  - Exploring the binding interaction of potent anticancer drug topotecan with human
      serum albumin: spectroscopic, calorimetric and fibrillation study.
AB  - This manuscript describes the interaction of the topoisomerase I inhibitor
      anticancer drug topotecan with human serum albumin using microcalorimetry,
      circular dichroism, and atomic force microscopy imaging techniques.
      Conformational change in albumin was ascertained from circular dichroism and
      synchronous fluorescence study that revealed a small but definitive partial
      unfolding of the protein structure upon drug binding. Isothermal titration
      calorimetry study indicated a favorable exothermic interaction with a binding
      affinity of the order of ~105 M-1 at 293.15 K. A 1:1 binding stoichiometry was
      established. The binding reaction was largely enthalpy dominated with negative
      standard molar Gibbs energy change. Ionic strength variation study revealed that
      non-polyelectrolytic forces played dominant role in the interaction and remained
      almost invariant at all salt concentrations. Upon complex formation, the
      stabilization of the protein structure against thermal denaturation occurred.
      Atomic force microscopy study enabled imaging of fibrils of the protein and its
      complex with topotecan.

PMID- 28760108
TI  - Retrospective Evaluation of Glycemic Control With Basal-Bolus or Neutral
      Protamine Hagedorn Insulin Regimens in Patients Receiving Continuous Enteral
      Nutrition Therapy in Medicine Wards.
AB  - Reasonable glycemic control is difficult to achieve in patients with diabetes
      mellitus (DM) receiving continuous enteral nutrition therapy (CENT). There are no
      solid evidence-based medicine guidelines regarding this issue in these patients.
      The purpose of this study was to determine if the use of a basal-bolus insulin
      regimen is more effective than neutral protamine Hagedorn (NPH) insulin alone in
      controlling blood glucose in non-critically ill patients with DM receiving CENT.
      We performed a retrospective, records-based review comparing basal-bolus with NPH
      insulin regimen in these patients, hospitalized in the internal medicine wards in
      our hospital. Number of hypoglycemic episodes, mean blood glucose, and time-to
      target (time needed to reach 3 successive glucose readings in the appropriate
      target of 140-180 mg/dL) were evaluated in each regimen. Mean blood glucose was
      199.22 mg/dL (95% confidence interval [CI], 179.8-218.5 mg/dL) in the basal-bolus
      vs 190.73 mg/dL (95% CI, 172.1-209.2 mg/dL) in the NPH insulin regimen ( P =
      .538). Time-to-target was an average of 3.65 +/- 1.75 days in the basal-bolus
      group and 4.33 +/- 2.42 days in the NPH group ( P = .364). There were no
      statistically significant differences in frequency of hypoglycemia ( P = .364).
      Rate of death was high (around 40%) in both groups. We conclude that hospitalized
      hyperglycemic patients receiving CENT can be treated by either basal-bolus or NPH
      insulin regimens. However, the overall glucose levels remain elevated during
      hospitalization irrespective of the insulin therapy. There is an urgent need to
      define glucose targets in this population of patients and to evaluate
      prospectively head-to-head different insulin protocols.

PMID- 28760110
TI  - Response to "We Support Elevated Protein Requirements in the Intensive Care Unit
      but Need New Solutions".

PMID- 28760109
TI  - Bariatric Surgery in Adolescents: Is Routine Nutrient Supplementation Sufficient
      to Avoid Anemia Following Bariatric Surgery?
AB  - BACKGROUND: Anemia following bariatric surgery is a known complication. To
      prevent nutrient deficiencies, adolescents require multivitamin/mineral
      supplementation following bariatric surgery. The purpose of this study was to
      investigate if routine multivitamin/mineral supplementation is sufficient to
      prevent anemia in adolescents undergoing bariatric surgery, particularly sleeve
      gastrectomy (SG), a procedure that may induce nutrient malabsorption. METHODS: We
      conducted a retrospective review of pediatric patients who underwent SG (34
      patients) and laparoscopic adjustable gastric banding (LAGB) (141 patients)
      (January 2006 through December 2013). We examined anemia marker levels (iron,
      ferritin, folate, B12, hemoglobin, and hematocrit) at first visit and 3, 6, and
      12 months postsurgery by repeated-measures analysis adjusting for weight loss.
      RESULTS: Following SG, folate levels decreased 3 and 6 months postsurgery but
      returned to baseline levels at 12 months. Furthermore, the SG group demonstrated
      lower folate levels compared with LAGB at 3 and 6 months. B12 levels decreased 6
      months post-SG but returned to baseline at 12 months. Following LAGB, B12 levels
      decreased 12 months postsurgery compared with baseline. Ferritin levels decreased
      3 months post-LAGB but returned to baseline levels at 6 months. There were no
      changes within groups or differences between groups in iron, hemoglobin, or
      hematocrit. CONCLUSIONS: While anemia did not occur in any patients while on
      recommended routine supplementation, folate levels were significantly reduced
      following SG and were lower in SG compared with LAGB patients. Additional folate
      supplementation seemed to improve folate levels, which highlights the importance
      of ongoing surveillance by primary care providers and the need for additional
      folate supplementation following SG.

PMID- 28760111
TI  - Differences in Prevalence of Muscle Wasting in Patients Receiving Peritoneal
      Dialysis per Dual-Energy X-Ray Absorptiometry Due to Variation in Guideline
      Definitions of Sarcopenia.
AB  - BACKGROUND: Muscle wasting is associated with increased risk for mortality. There
      is no agreed universal definition for muscle wasting (sarcopenia), and we wished
      to determine whether using different criteria altered the prevalence in patients
      treated by peritoneal dialysis. METHODS: We measured lean body and appendicular
      lean mass indices in 325 outpatients by dual-energy x-ray absorptiometry,
      comparing muscle mass with that used to define muscle wasting (sarcopenia) by
      various clinical guideline publications. RESULTS: Lean body and appendicular lean
      mass indices did not differ by sex: female, 17.7 +/- 4.6 kg/m2; male, 17.4 +/-
      4.3; female, 6.9 (5.6-8.5) kg/m2; male, 6.7 (5.3-8.3), respectively. Depending on
      the criteria, the prevalence of muscle wasting varied from 2.2%-31.3% for women
      and 25.1%-75.6% for men. Male patients were older (58.3 +/- 16 vs 53.4 +/- 15.7
      years). Criteria based on cutoffs derived from young healthy patients gave the
      higher prevalence rates. The prevalence of muscle wasting was not associated with
      dialysis adequacy, estimated protein intake, duration of dialysis treatment,
      comorbidity, diabetes, or ethnicity. The prevalence of sarcopenic obesity was low
      (<5% females, 7% males). CONCLUSION: We found that the prevalence varied markedly
      depending on the cutoff criteria used to define muscle wasting. Very few patients
      had sarcopenic obesity. The higher prevalence for males requires further study
      but was not associated with dialysis treatment. Our study highlights the need for
      agreed criteria to define pathologic muscle wasting from that which is age
      associated to allow for interventional screening programs.

PMID- 28760112
TI  - We Support Elevated Protein Requirements in the Intensive Care Unit but Need New
      Solutions.

PMID- 28760113
TI  - Editor's Note.

PMID- 28760114
TI  - Assessing Selenium, Manganese, and Iodine Status in Pediatric Patients Receiving
      Parenteral Nutrition.
AB  - BACKGROUND: Pediatric patients who are receiving parenteral nutrition (PN)
      unsupplemented with trace minerals can become deficient. Due to shortages in
      trace mineral products and the 2004 American Society for Parenteral and Enteral
      Nutrition report stating that individualized trace element supplementation may be
      warranted, a review was conducted concerning the trace minerals selenium (Se),
      manganese (Mn), and iodine (I). METHOD: A retrospective review of pediatric
      patients receiving PN that contained Se and Mn was conducted to determine if a
      difference existed between them and patients receiving PN without Se and Mn.
      Statistical analysis was done to assess a difference between trace mineral levels
      and the time to deficiency between supplemented and unsupplemented patients.
      Unsupplemented I patients had urine I levels assessed to determine deficiencies
      in patients receiving PN. RESULTS: Plasma Se levels were measured at a mean of 20
      days for supplemented patients (n = 131) and 19 days for nonsupplemented patients
      (n = 57) with no difference between groups ( P = .2973). Plasma Mn levels were
      measured at a mean of 28 days, showing no statistical difference ( P = .721). Of
      the 177 nonsupplemented I patients, 74% demonstrated I deficiencies without
      supplementation. CONCLUSIONS: Time to the development of a Se, Mn, or I
      deficiency is important to guide supplementation of exclusive PN in children when
      trace mineral products are short in supply. Our retrospective experience supports
      assessment of the trace minerals Se at 21 days and Mn at 30 days. It also
      suggests that some pediatric patients receiving PN are deficient in I.

PMID- 28760115
TI  - A Model of Acute Antibody-Mediated Renal Allograft Rejection in the Sensitized
      Rata.
AB  - OBJECTIVES: Antibody-mediated rejection in transplant recipients with preexisting
      donor-specific antibodies is a challenging clinical situation. However, we lack
      suitable animal models to study this scenario. The aim of this study was to
      develop an animal model of acute antibody-mediated rejection of renal allografts
      in sensitized recipients. MATERIALS AND METHODS: We used major histocompatibility
      complex class I and II incompatible rat strains (Dark Agouti RT1av1 and Lewis
      RT1l), which develop aggressive rejection. Recipient Lewis rats were immunized
      with donor strain spleen cells 5 days before surgery to induce donor-specific
      antibodies. Rats underwent bilateral nephrectomy and orthotopic transplant of the
      donor kidney. To minimize T-cell-mediated rejection while allowing the
      development of donor-specific antibodies, recipient animals were given tacrolimus
      starting the day before surgery. RESULTS: Hyperacute rejection was not seen, but
      acute graft dysfunction was evident on day 1 with a rapid deterioration of graft
      function by day 3. Histologic damage featured glomerulopathy, capillaritis,
      capillary thrombosis, and acute tubular injury. Recipients exhibited high serum
      levels of donor-specific antibodies and deposition of immunoglobulin G and C4d on
      graft endothelium. Immunostaining showed substantial endothelial damage, fibrin
      deposition in glomerular and peritubular capillaries, and infiltrates of
      macrophages, neutrophils, and natural killer cells. T-cell activation was
      efficiently suppressed by tacrolimus. CONCLUSIONS: We have developed a clinically
      relevant model of acute antibody-mediated rejection in recipients with
      preexisting donor-specific antibodies, which is suitable for testing novel
      therapies.

PMID- 28760116
TI  - Impact of Sex Disparities on Outcomes of Living-Donor Kidney Transplant in Egypt:
      Data of 979 Patients.
AB  - OBJECTIVES: Renal transplant is the criterion standard for treatment of end-stage
      renal disease. The effects of disparities between men and women on renal
      transplant outcomes have been evaluated in many studies but with debatable
      results. It has been suggested that female kidney donors have poor outcomes after
      transplant compared with male kidney donors, especially when implanted in a male
      recipient. The aim of the study was to evaluate the effects of sex on living
      donor kidney transplant outcome. MATERIALS AND METHODS: The data of 979 patients
      who underwent living-donor kidney transplant from January 2000 to December 2010
      at a single center were reviewed retrospectively. The patients were divided into
      4 groups according to recipient and donor sex: male donor-to-male recipient (n =
      307), male donor-to-female recipient (n = 132), female donor-to-male recipient (n
      = 411), and female donor-to-female recipient (n = 129). We compared the
      demographic characteristics, posttransplant rejection and complications, and
      graft and patient survival rates among the groups. RESULTS: Male recipients were
      older than female recipients, whereas male donors were younger than female donors
      (P < .001). No statistically significant differences were shown regarding
      recipient body mass index, ischemia time and time to diuresis, and acute and
      chronic rejection rates between the groups. Graft (P = .947) and patient (P =
      .421) survival rates were comparable between groups. CONCLUSIONS: Donor and
      recipient sex had no significant effect on outcomes of living-donor renal
      allograft recipients.

PMID- 28760117
TI  - Successful Transplant of a Nonagenarian Liver Graft With Fully Replaced Right
      Hepatic Artery Reconstruction.
AB  - Organ shortage and increasing donor age in liver transplant are stimulating
      transplant centers to accept otherwise discarded grafts due to donor age or
      vascular abnormalities; nevertheless, the use of nonagenarian donor grafts is
      uncommon because advanced age is associated with a higher risk of ischemic-type
      biliary lesions and worse long-term graft survival. We herein report the case of
      a 90-year-old donor with fully replaced right hepatic artery. After back-table
      vascular assessment, the donor right hepatic artery was anastomosed end-to-end
      with the gastroduodenal artery with 2 polypropylene 8/0 running sutures. Even if
      the back-table reconstruction of a replaced right hepatic artery is not
      associated with an enhanced risk of posttransplant vascular complications,
      vascular abnormalities might discourage the use of otherwise acceptable elderly
      grafts. The present case underscores that elderly liver grafts should not be
      discarded per se even in the presence of vascular variants.

PMID- 28760118
TI  - Renal Transplant in the Abnormal Bladder: Long-Term Follow-Up.
AB  - OBJECTIVES: Normal urinary bladder stores urine at low pressure, does not leak,
      and completely empties by natural voiding. An abnormal bladder may be due to
      neurologic or urologic disorders that render the bladder of small capacity, of
      high storage pressure, or of poor compliance. The aim of this study was to
      determine the long-term outcomes of renal transplant in patients with abnormal
      bladders. MATERIALS AND METHODS: We retrospectively compared 30 transplanted
      kidneys in 25 patients with abnormal bladders with a control group comprising 30
      grafts transplanted simultaneously during the same period of time (1990-2014) in
      30 patients without bladder abnormality. Patient demographics, graft function,
      survival, and postoperative complications were compared. RESULTS: Patients with
      abnormal bladders received transplants at a younger age than the control group
      (32 +/- 17 vs 47 +/- 12 y; P <. 001). Graft survival was not significantly
      different between the study and the control groups at 1 (90% vs 97%; P = .30), 3
      (88% vs 91%; P = .67), and 5 years (82% vs 87%; P = .68). On long-term follow-up
      (20 years), 19 grafts (63%) were functioning in the study group compared with 25
      grafts (83%) in the control group, suggesting inferior survival in those with an
      abnormal bladder after the first 10 years of transplant. In the abnormal bladder
      group, there was higher incidence of urologic complications (93% vs 50%; P<.001).
      CONCLUSIONS: Despite the earlier age at transplant, the previous urologic
      operations, and the high incidence of urinary tract infection after renal
      transplant, graft survival and functions after renal transplant were not
      significantly different between patients with abnormal and normal bladders over
      at least the first 10 years. Therefore, it is safe to transplant into abnormal
      bladders once they have been assessed, reconstructed if necessary, and managed
      appropriately.

PMID- 28760119
TI  - Autologous Stem Cell Rescue for Graft Failure of Second Allogeneic Stem Cell
      Transplant After Engraftment of Primary Allogeneic Transplant.
AB  - Here, we describe a case of primary graft failure with severe sepsis in a boy who
      experienced frequent relapses of osteosarcoma. The patient had undergone
      haploidentical bone marrow transplant after engraftment of unrelated cord blood
      transplant performed 10 months earlier. Considering his severe condition, we
      transfused autologous peripheral stem cells along with a single dose of etoposide
      (50 mg/m2). Granulocyte engraftment was confirmed on human leukocyte antigen
      microsatellite analysis of bone marrow on day 14. Although the patient died due
      to respiratory failure, transfusion of autologous hematopoietic stem cells is a
      reasonable rescue option for graft failure even in patients whose background
      hematopoiesis is reconstituted by a first donor.

PMID- 28760120
TI  - Platelet-rich plasma: Everything new may not be good enough!

PMID- 28760121
TI  - Comparison of intravenous and intra-articular tranexamic acid in reducing blood
      loss in primary total knee replacement.
AB  - OBJECTIVES: This study aims to compare the efficacy and safety of intra-articular
      tranexamic acid (TA) versus intravenous (IV) TA in the reduction of perioperative
      blood loss and the degree of early postoperative complications associated with
      primary unilateral cemented total knee replacement. PATIENTS AND METHODS: This
      prospective randomized study included 90 patients (36 males, 54 females; mean age
      68.7 years; range 47 to 82 years) with knee osteoarthritis undergoing a
      unilateral cemented total knee replacement. Patients were randomized into three
      groups: group 1 received TA intravenously (dose 10 mg/kg) 20 minutes
      preoperatively and three hours after first dose, group 2 received TA (dose 3 g)
      locally (intra-articular) into surgical site, and group 3 did not receive TA. We
      measured perioperative blood loss, volume of drained blood in 24 hours
      postoperatively, overall blood loss, decrease in hemoglobin and hematocrit
      levels, and amount of blood transfusion. RESULTS: There were no differences
      between the groups in terms of patient preoperative demographics. Local or IV
      administration of TA significantly reduced the number of blood transfusions and
      blood losses in drainage. Intravenous application of TA was associated with
      statistically significantly higher hemoglobin and hematocrit levels and lower
      overall postoperative blood losses. No serious complications were observed in any
      of the groups. CONCLUSION: Intra-articular TA was equally effective as IV regimen
      in reducing the number of blood transfusions. However, IV administration of TA
      was associated with overall lower blood loss. Our results showed that IV
      administration of TA during total knee replacement is superior compared to intra
      articular administration of TA.

PMID- 28760122
TI  - Comparison of two medial epicondylectomy techniques in cubital tunnel syndrome.
AB  - OBJECTIVES: This study aims to compare partial medial epicondylectomy (PMe) and
      distal medial epicondylectomy (DMe) techniques in terms of sensory and motor
      improvements, functional results and complications. PATIENTS AND METHODS: The
      study included a total of 59 cubital tunnel syndrome patients (37 males, 22
      females; mean age 42.3 years; range 23 to 80 years). Of the patients, DMe was
      applied on 30 and PMe was applied on 29. Patients were evaluated with Wilson
      Krout scores, Semmes-Weinstein Monofilament (SWM) test, and grip and pinch
      strength measurements preoperatively and at postoperative third, sixth, and 12th
      months. Both groups' pre- and postoperative intragroup and intergroup results
      were compared. RESULTS: Wilson Krout scores in postoperative checks were better
      with DMe compared to PMe. The improvement in SWM test scores was statistically
      significant for only DMe. The improvement in grip strength, lateral pinch and
      terminal pinch measurements in DMe group was significant at postoperative third
      month. In PMe group, significant improvement for these measurements was obtained
      at postoperative sixth month. The only complication observed with DMe was
      tenderness developing over the medial epicondyle. Painful subluxation of the
      nerve associated with paresthesia was detected in four patients in PMe group.
      CONCLUSION: Compared to PMe, DMe offers more satisfactory subjective results.
      Motor functional recovery occurs earlier with DMe. DMe appears to have lower
      complication rates.

PMID- 28760123
TI  - Is locked compressive intramedullary nailing for adult humerus shaft fractures
      advantageous?
AB  - OBJECTIVES: This study aims to evaluate the radiological and functional outcomes
      of locked compressive intramedullary nailing (IMN) cases in adult humerus shaft
      fractures. PATIENTS AND METHODS: A total of 24 patients (12 males, 12 females;
      mean age 42 years; range 23 to 55 years) with humerus fractures were treated with
      locked compressive IMN at the Orthopedics and Traumatology Clinic, Antalya
      Training and Research Hospital between December 2009 and March 2015. Fluoroscopy
      was used only to check fracture reduction before the reaming procedure. Of the
      patients, closed IMN was performed in 21, while open reduction was performed in
      three. Lock screws were locked without fluoroscopy in all patients. Of the
      patients in whom open reduction was performed, radial nerve lesion developed in
      one. Anteroposterior and lateral graphs of all patients were taken
      postoperatively. Fracture union was assessed according to existence of the
      fracture line and the callus tissue in the anteroposterior and lateral graphs.
      The Constant-Murley scoring system was used for functional evaluation. The mean
      follow-up period was 24 months (range 12 to 72 months). Finite element analysis
      was performed for the stress distribution on fracture site. RESULTS: Radiological
      fracture union was achieved in all patients at mean 14.8 weeks (range 12 to 17
      weeks). The Constant-Murley score was mean 90 (range 72 to 100). There was a
      statistically significant, negative and strong correlation between union period
      and the Constant-Murley score (r=-0.78, p<0.001). In one patient who developed
      postoperative radial nerve symptoms, all functions were regained in fourth month.
      No infection occurred in any patient. In two patients, tip of the nail remained
      high. Of these patients, one developed impingement findings, and the other
      patient had no problems. CONCLUSION: Treatment of humerus shaft fractures with
      locked compressive IMN provides sufficient fixation and early movement
      opportunity in the shoulder and elbow joints, and gives satisfactory radiological
      and functional results.

PMID- 28760124
TI  - Interphalangeal arthrodesis using an intramedullary nitinol implant: a
      prospective study.
AB  - OBJECTIVES: This study aims to evaluate the nitinol (X-Fuse(r)) implant in
      arthrodesis of the distal interphalangeal and the thumb joints with respect to
      bone fusion and clinical efficiency. PATIENTS AND METHODS: This prospective study
      included 24 consecutive patients (7 males, 17 females; mean age 56.8 years; range
      27 to 79 years) with nitinol (X-Fuse(r)) implants in their 41 joints. All
      patients were followed-up clinically and radiographically with respect to fusion,
      complications and outcome at a minimum of 14 months postoperatively (mean 28+/-6
      months). X-rays, Disabilities of the Arm, Shoulder and Hand, and visual analog
      scale scores were recorded preoperatively and at postoperative fifth week, third
      month, first year, and subsequent visits. RESULTS: The Disabilities of the Arm,
      Shoulder and Hand score improved significantly from preoperative 37.7 points to
      postoperative 14.5 points at first year. The visual analog scale score improved
      significantly from preoperative 5.5 to postoperative 0.85 points at first year.
      Failure to fuse only occurred in two joints (5%), resulting in fusion after
      reoperation. No other severe complications such as deep infection, intraoperative
      fracture, wound healing problems or regional dystrophy were observed. CONCLUSION:
      The X-Fuse(r) implant may be a reliable alternative method for finger joint
      arthrodesis.

PMID- 28760125
TI  - Comparison of the effects of human recombinant epidermal growth factor and
      platelet-rich plasma on healing of rabbit patellar tendon.
AB  - OBJECTIVES: This study aims to compare the histological healing process and gene
      expression profile in tendon after the administration of human recombinant
      epidermal growth factor (hrEGF) and platelet-rich plasma (PRP). MATERIALS AND
      METHODS: A total of 24 mature New Zealand white rabbits (6-month-old; weight 2.5
      3.0 kg) were used in the study. Patellar tendons of rabbits were tenotomized and
      then repaired. Rabbits were separated into three groups and repair areas were
      injected with 1 mL hrEGF in group 1 (n=9) and 1 mL PRP in group 2 (n=9). No
      injection was performed in group 3 (controls, n=6). Tissue samples were obtained
      from the repaired patellar tendons of three rabbits each from groups 1 and 2 and
      of two rabbits from group 3 at the end of the first, second, and fourth weeks,
      and these tissues were histologically and genetically assessed. Expression levels
      of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and
      chemokine receptors (CXCR1, CXCR2) were examined. RESULTS: The frequency of
      neovascularization was detected to be higher in group 1 compared to group 3 at
      the end of the second and fourth weeks (p=0.018 and p=0.009, respectively). Group
      1 was detected to show more increase in terms of the prevalence of tenocytes
      (p=0.014 and p=0.009, respectively) at the end of the second week, and in terms
      of collagen intensity at the end of the fourth week (p=0.0018 and p=0.034,
      respectively) compared to groups 2 and 3. Highest levels of TNF-alpha, IL-6, and
      IL-8 were detected in group 1, followed by groups 2 and 3 at all time points.
      Highest CXCR2 gene expression was detected in group 1. CONCLUSION: Compared to
      PRP, hrEGF caused more increase in healing tissue at neovascularization,
      tenocyte, fibroblast, collagen, and tissue macrophage levels; and higher levels
      of TNF-alpha, IL-6, IL8, and CXCR2. Intralesional hrEGF administration can
      effectively accelerate tendon healing.

PMID- 28760126
TI  - Simple method for increasing drug elution from polymethylmethacrylate bone
      cement.
AB  - OBJECTIVES: This study aims to investigate the effects of the use of citric acid
      and sodium bicarbonate mixture as an effervescent in polymethylmethacrylate bone
      cement in terms of better drug elution. PATIENTS AND METHODS: Multiple cylinder
      cement blocks each containing 10 g of glucose and different amounts of
      effervescent (E), with different numbers of pieces (P), surface areas, volumes,
      and porosities were prepared. Physical properties of all blocks were calculated.
      Blocks were placed in jars containing saline solutions and the released glucose
      concentrations were measured at predefined intervals. Correlations between
      elution rate and physical properties were defined. RESULTS: Elution rates were
      significantly higher in samples with effervescent. At the end of 45th day, E0P1
      released mean 21% of its glucose content. This value was 38%, 61%, 82% and 88%
      for E0P2, E0P4, E2P1 and E4P1, respectively. Strong correlations were detected
      between water absorption ratio, surface areas, porosity and glucose elution rates
      (r=0.942, p<0.01; r=0.894, p<0.05; r=0.918, p<0.05). CONCLUSION: Using sodium
      bicarbonate and citric acid as effervescent in bone cement provides satisfactory
      porosity development for better antibiotic elution. This method may be useful
      when a monolithic spacer and better local antibiotic elution are required.

PMID- 28760127
TI  - Does platelet-rich plasma have a favorable effect in the early stages of steroid
      associated femoral head osteonecrosis in a rabbit model?
AB  - OBJECTIVES: This study aims to investigate the effect of platelet-rich plasma
      (PRP) on femoral head osteonecrosis and compare it with bone marrow injection and
      core decompression. MATERIALS AND METHODS: A total of 30 healthy, adult, male New
      Zealand white rabbits (mean weight 2.25+/-0.15 kg; range 2.0 to 2.5 kg) were used
      in the study. To create experimental osteonecrosis in all rabbits, 40 mg/kg
      methylprednisolone acetate was applied intramuscularly. Rabbits were randomly
      allocated into three groups with 10 rabbits in each: drilling group, PRP group,
      and bone marrow group. The non-drilled hips of the drilling group were identified
      as the control group. RESULTS: Rate of necrotic bone was lower in the PRP group
      compared to other groups. Highest rate of necrotic bone was detected in the
      control group. New bone formation rate was higher in the PRP group compared to
      other groups. Lowest new bone formation rate was determined in the control group.
      Inflammatory reaction rate was higher in the PRP group compared to other groups.
      CONCLUSION: Platelet-rich plasma injection may play a positive role in the
      treatment of steroid-associated osteonecrosis in a rabbit model.

PMID- 28760128
TI  - Analysis of musculoskeletal dysmorphic abnormalities of 20 fetuses.
AB  - OBJECTIVES: This study aims to report rates of skeletal abnormalities and their
      risk factors in light of information obtained in a fetal autopsy series. PATIENTS
      AND METHODS: The study included 20 fetuses (11 males, 8 females and 1 ambiguous
      genitalia; mean age 19.3+/-4.0 weeks; range 16 to 32 week) who underwent autopsy
      in our hospital between January 2013 and March 2015. Fetuses were systematically
      classified according to age, gender, family history, abortus week, abortus type,
      and extremity and organ abnormalities. Skin biopsies were performed for genetic
      evaluation. Radiographic, pathologic and genetic findings were classified.
      RESULTS: Except one spontaneous abortus, all cases were applied medical abortus
      (94.1%). Genetic diagnosis could not be established in seven cases, whereas
      genetic disorders were identified in 13 cases: two trisomy 13, two trisomy 18,
      one (triploidi) 69,XXY, two arthrogryposis multiplex congenita, one osteogenesis
      imperfecta, one lethal multiple pterygium, one Saldino-Noonan syndrome, one
      teratogenic drug effect, one perinatal lethal hypophosphatasia, and one Beckwith
      Wiedemann syndrome. Decreased fetal movement was one of the most frequently
      observed findings. Consanguineous marriage, oligohydramnios, drug addiction of
      the mother, teratogenic exposure, and other systemic abnormalities were risk
      factors. CONCLUSION: Skeletal dysplasias are rare diseases. Clinicians should be
      careful for skeletal abnormalities in perinatal period follow-ups.

PMID- 28760129
TI  - Management of solitary fibrous tumors localized in extremity: case series and a
      review of the literature.
AB  - OBJECTIVES: This study aims to evaluate the clinical characteristics and
      treatment results of patients with a diagnosis of solitary fibrous tumor
      localized in extremity. PATIENTS AND METHODS: Clinical findings, treatment
      methods, clinical outcomes and treatment failures of seven patients (3 males, 4
      females; mean age 49.7+/-20.7 years; range 22 to 79 years) diagnosed as solitary
      fibrous tumor localized in extremity between January 2005 and December 2016 were
      evaluated retrospectively. RESULTS: Most frequent localization was the thigh
      (42.8%, n=3). Mean tumor size was 10.8+/-2.4 cm (range 8-15 cm). All patients
      applied with painless mass and all had primary tumor. All patients had localized
      disease at the time of diagnosis. Postoperative mean follow-up duration was 44.4
      months (range 13-121 months). Marginal resection was performed in two patients at
      low risk group while wide resection was performed in other patients at moderate
      and high risk groups. Patients who underwent marginal resection were performed
      adjuvant radiotherapy. No recurrence or metastasis was detected in any of the
      patients during follow-up. CONCLUSION: In the treatment of solitary fibrous
      tumors localized in extremity, marginal resection together with radiotherapy may
      be an alternative treatment method for patients in low risk group according to
      risk stratification model, for whom wide resection is not possible. Wide
      resection is recommended in moderate and high risk groups to decrease local
      recurrence and metastasis risks.

PMID- 28760130
TI  - Neglected bilateral congenital dislocation of the patella.
AB  - Congenital dislocation of the patella is a disorder that presents with
      dysfunction in extensor mechanism. Although congenital dislocation of the patella
      mostly occurs in children with genetic disorders, it may also occur in totally
      healthy children, despite rarely. In this article, we report a 16-year-old male
      patient who referred to our clinic with complaints of gait disturbance, frequent
      falls, and muscular weakness in lower extremity. The patient had no complaints
      during walking, but had difficulty in running and walking up and down the stairs.
      It was observed that the range of motion of the knee joint was completely
      painless and the quadriceps muscle strength was evaluated as 3/5. An evaluation
      of computed tomography and magnetic resonance imaging results showed that the
      patella was dislocated. It became clear with magnetic resonance imaging that
      extensor mechanism was continuous but patellar tendon was not attached to its
      anatomical position. Surgical treatment was not planned because the patient did
      not describe any pain complaint and there was no limitation of joint movement, he
      could walk without support and without device and also refused to be operated.
      The choice of treatment should be based on the patient's preference, and pain and
      functional status.

PMID- 28760131
TI  - Atypical injury of radial nerve after humeral shaft fracture.
AB  - As general opinion, conservative treatment is usually suggested for closed
      humeral shaft fractures with radial nerve palsy; however, some authors advocate
      early surgical exploration, particularly for spiral fractures of the humerus
      accompanied with radial nerve palsy. In this article, we present a case of radial
      nerve palsy after fracture of the proximal-middle third of humeral shaft. A
      surgical exploration of the nerve revealed that the sharp tip of the bony
      fragment at fracture site was penetrated into the nerve and separated the nerve
      as two bands, almost like a "buttonhole" injury. We think that this kind of an
      atypical injury of the radial nerve would most probably not recover with
      conservative management; or the nerve may even be damaged worse by the fragment
      in case of a possible movement on the nerve's fracture line or by being trapped
      by callus formation during healing. In this case report, we aimed to raise
      awareness among orthopedists regarding such and similar atypical injuries of the
      radial nerve.

PMID- 28760132
TI  - Ulna fracture and medial meniscal tear resulting from dog-related injuries.
AB  - In this article, we present two middle-aged female patients with ulna fracture or
      medial meniscal tear resulting from dog-related injuries, which are not common.
      Both patients mentioned that pain started after their dogs pulled away their
      collar ropes strongly and suddenly. Both patients had postmenopausal osteoporosis
      and degenerative osteoarthritis. For this reason, ulna fracture and meniscus tear
      had developed with low-energy trauma resulting from dog-related injuries.

PMID- 28760133
TI  - Surface ECG interatrial block-guided treatment for stroke prevention: rationale
      for an attractive hypothesis.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia and is
      associated with stroke, cognitive impairment, and cardiovascular death. Some
      predisposing factors - as aging, diabetes, hypertension - induce and maintain
      electrophysiological and ultrastructural remodeling that usually includes
      fibrosis. Interatrial conduction disturbances play a crucial role in the
      initiation of atrial fibrosis and in its associated complications. The diagnosis
      of interatrial blocks (IABs) is easy to perform using the surface ECG. IAB is
      classified as partial when the P wave duration is >=120 ms, and advanced if the P
      wave also presents a biphasic pattern in II, III and aVF. IAB is very frequent in
      the elderly and, particularly in the case of the advanced type, is associated
      with AF, AF recurrences, stroke, and dementia. The anticoagulation in elderly
      patients at high risk of AF without documented arrhythmias is an open issue but
      recent data suggest that it might have a role, particularly in elderly patients
      with structural heart disease, high CHA2DS2VASc (Congestive heart failure/left
      ventricular dysfunction, Hypertension, Age >= 75 [doubled], Diabetes, Stroke
      [doubled] - Vascular disease, Age 65-74, and Sex category [female]), and advanced
      IAB. In this debate, we discuss the association of surface ECG IAB, a marker of
      atrial fibrosis, with AF and stroke. We also present the rationale that justifies
      further studies regarding anticoagulation in some of these patients.

PMID- 28760135
TI  - The first data on the innervation of the lophophore in the rhynchonelliform
      brachiopod Hemithiris psittacea: what is the ground pattern of the lophophore in
      lophophorates?
AB  - BACKGROUND: The nervous system in brachiopods has seldom been studied with modern
      methods. An understanding of lophophore innervation in adult brachiopods is
      useful for comparing the innervation of the same lophophore type among different
      brachiopods and can also help answer questions about the monophyly of the
      lophophorates. Although some brachiopods are studied with modern methods,
      rhynchonelliform brachiopods still require investigation. The current study used
      transmission electron microscopy, immunocytochemistry, and confocal laser
      scanning microscopy to investigate the nerve system of the lophophore and
      tentacles in the rhynchonelliform Hemithiris psittacea. RESULTS: Four
      longitudinal nerves pass along each brachium of the lophophore: the main,
      accessory, second accessory, and lower. The main brachial nerve extends at the
      base of the dorsal side of the brachial fold and gives rise to the cross nerves,
      passing through the extracellular matrix to the tentacles. Cross nerves skirt the
      accessory brachial nerve, branch, and penetrate into adjacent outer and inner
      tentacles, where they are referred to as the frontal tentacular nerves. The
      second accessory nerve passes along the base of the inner tentacles. This nerve
      consists of Upsilon-like parts, which repetitively skirt the frontal and lateral
      sides of the inner tentacle and the frontal sides of the outer tentacles. The
      second accessory nerve gives rise to the latero-frontal nerves of the inner and
      outer tentacles. The abfrontal nerves of the inner tentacles also originate from
      the second accessory nerve, whereas the abfrontal nerves of the outer tentacles
      originate from the lower brachial nerve. The lower brachial nerve extends along
      the outer side of the lophophore brachia and gives rise to the intertentacular
      nerves, which form a T-like branch and penetrate the adjacent outer tentacles
      where they are referred to as abfrontal nerves. The paired outer radial nerves
      start from the lower brachial nerve, extend into the second accessory nerve, and
      give rise to the lateroabfrontal tentacular nerves of the outer tentacles.
      CONCLUSIONS: The innervation of the lophophore in the rhynchonelliform Hemithiris
      psittacea differs from that in the inarticulate Lingula anatina in several ways.
      The accessory brachial nerve does not participate in the innervation of the
      tentacles in H. psittacea as it does in L. anatina. The second accessory nerve is
      present in H. psittacea but not in L. anatina. There are six tentacular nerves in
      the outer tentacles of H. psittacea but only four in all other brachiopods
      studied to date. The reduced contribution of the accessory brachial nerve to
      tentacle innervation may reflect the general pattern of reduction of the inner
      lophophoral nerve in both phoronids and brachiopods. Bryozoan lophophores, in
      contrast, have a weakened outer nerve and a strengthened inner nerve. Our results
      suggest that the ancestral lophophore of all lophophorates had a simple shape but
      many nerve elements.

PMID- 28760134
TI  - Life-threatening bleeding from gastric dieulafoy's lesion in a pregnant woman
      with hellp syndrome: a case report and literature review.
AB  - BACKGROUND: Dieulafoy's lesion (DL) is one of the rare causes of upper
      gastrointestional bleeding. This disease is characterized by small sub-mucosal
      arteriole that eroded the stomach mucosa and cause severe upper GI bleeding
      without obvious ulceration. The most common location is fundus area of stomach
      and usually affects patients over 50 years of age with multiple comorbidities.
      CASE PRESENTATION: We report a case of life-threatening bleeding from DL during
      late pregnancy 31 weeks. Hemoclips were used twice through upper endoscopy with
      successful hemostasis. Unfortunately, she developed HELLP syndrome diagnosed 5
      days after the GI bleeding was stopped. Her pregnancy had to be terminated with
      delivery of a premature infant. She recovered from her illness and discharged
      from hospital uneventfully. There is no current report in literature of DL in
      pregnant woman subsequently suffered HELLP syndrome. CONCLUSION: Endoscopic
      hemoclip application is an effective technique in the treatment of upper GI
      bleeding from DL. For this patient, laparoscopic surgery or combination therapy
      before pregnancy may have been a suitable treatment on preventing rebleeding.

PMID- 28760136
TI  - Development of a high-density linkage map and mapping of the three-pistil gene
      (Pis1) in wheat using GBS markers.
AB  - BACKGROUND: The wheat mutant line three-pistil (TP) exhibits three pistils per
      floret. As TP normally has two or three seeds in each of the florets on the same
      spike, there is the possibility of increasing the number of grains per spike.
      Therefore, TP is a highly valuable mutant for breeding and for the study of
      floral development in wheat. To map the three-pistil gene (Pis1), genotyping-by
      sequencing single-nucleotide polymorphism (GBS-SNP) data from an F2 mapping
      population (CM28 * CM28TP) was used to construct a genetic map that is of
      significant value. RESULTS: In the present study, a high-density genetic map of
      wheat containing 2917 GBS-SNP markers was constructed. Twenty-one linkage groups
      were resolved, with a total length of 2371.40 cM. The individual chromosomes
      range from 2.64 cM to 454.55 cM with an average marker density of 0.81 cM. The
      Pis1 gene was mapped using this high-resolution map, and two flanking SNP markers
      tightly linked to the gene, M70 and M71, were identified. The Pis1 is 3.00 cM
      from M70 and 1.10 cM from M71. In bread wheat genome, M70 and M71 were found to
      delimit a physical distance of 3.40 Mb, which encompasses 127 protein-coding
      genes. To validate the GBS-generated genotypic data and to eliminate missing
      marker data in the Pis1 region, five Kompetitive Allele-Specific PCR (KASP)
      assays were designed from corresponding GBS sequences, which harbor SNPs that
      surround Pis1. Three KASP-SNP markers, KM70, KM71, and KM75, were remapped to the
      Pis1 gene region. CONCLUSIONS: This work not only lays the foundation for the map
      based cloning of Pis1 but can also serve as a valuable tool for studying marker
      trait association of important traits and marker-assisted breeding in wheat.

PMID- 28760137
TI  - Prevalence and clinical profile of metabolic syndrome in longevity: study from
      Guangxi Zhuang Autonomous Region, China.
AB  - BACKGROUND: Metabolic syndrome (MetS) was a risk factor for cardiovascular
      diseases, yet the prevalence of MetS among nonagenarians and centenarians was
      rarely reported. Here we investigated the prevalence of MetS and its components
      among nonagenarians and centenarians in our Zhuang population from Bama, Guangxi
      Zhuang Autonomous Region, China. METHOD: In Bama area, there registered 881
      individuals who lived more than 90 years old in 269,800 local residents and our
      study involved 307 long-lived participants and 486 local younger (35-68 years)
      persons, as controls. MetS was defined according to the revised National
      Cholesterol Education Program's Adult Treatment Panel III (NCEP ATPIII) criteria.
      RESULTS: The overall prevalence estimates of MetS among longevity group were
      28.0% based on NCEP ATPIII criteria. The most common metabolic component was
      elevated blood pressure (61.1%), followed by raised fasting glucose (39.1%) and
      low high-density lipoprotein cholesterol (low HDL-C) (28.0%). The prevalence of
      MetS and abdominal obesity in women (33.6% and 22.1% respectively) was higher
      than that of men (19.8% and 3.7% respectively) (Prange < .001-0.019). Compared
      with controls, long-lived individuals were more likely to have two or more
      metabolic abnormalities (Prange < 0.001), and less likely to have zero or one
      metabolic abnormality (Prange < 0.001-0.020). CONCLUSION: This study showed
      substantiality the prevalence and clinical profile of MetS in longevity
      population in Guangxi Zhuang Autonomous Region, China.

PMID- 28760138
TI  - Age-standardized mortality rates related to viral hepatitis in Brazil.
AB  - BACKGROUND: Liver-related mortality has been increasing worldwide. We aimed to
      estimate the age-standardized mortality rates from viral hepatitis in Brazil.
      METHODS: The Brazilian National Death Registry was analyzed from 2008 to 2014.
      Viral hepatitis deaths were defined by the following ICD-10 codes in the death
      certificate: hepatitis A [B15.0; B15.9]; hepatitis B [B16.2; B16.9; B18.1];
      hepatitis C [B17.1; B18.2]; hepatitis Delta [B16.0; B16.1; B18.0; B17.0] and
      other viral hepatitis [B17.2; B17.8; B18.8; B18.9; B19.0; B19.9]. Crude mortality
      rates were calculated by the ratio between total number of deaths and estimated
      population. Mortality rates were age-standardized by the direct method using the
      WHO standard population. RESULTS: Thirty four thousand ,nine hundred seventy
      eight deaths had viral hepatitis mentioned in their death certificate [65% male,
      aged 58 years, 73% associated with hepatitis C]. Age-standardized mortality rate
      (95% CI) due to viral hepatitis was 2.695 (2.667-2.724) deaths per 100,000
      inhabitants: South region had the higher rates [3.997 (3.911-4.085)]. Mortality
      rates associated with hepatitis A and Delta were 0.032 (0.029-0.035) and 0.028
      (0.025-0.031), respectively. Hepatitis C mortality rates were 4-fold higher than
      those associated with hepatitis B [1.964 (1.940-1.989) vs 0.500 (0.488-0.512)].
      South region had the higher rates for hepatitis C [3.163 (3.087-3.241)] and North
      had the higher rates for hepatitis A [0.066 (0.049-0.087)], B [0.986 (0.918
      1.058)] and Delta [0.220 (0.190-0.253)]. CONCLUSION: Viral hepatitis remains a
      major public health issue in Brazil. Mortality rates were not homogeneous across
      the country, suggesting that health policies should be customized according to
      geographical location.

PMID- 28760139
TI  - Selection plays the hand it was dealt: evidence that human adaptation commonly
      targets standing genetic variation.
AB  - Using a powerful machine learning approach, a recent study of human genomes has
      revealed widespread footprints of recent positive selection on standing genetic
      variation.

PMID- 28760141
TI  - Pharmacovigilance in Israel - tools, processes, and actions.
AB  - BACKGROUND: Due to the limited safety data available at the time that a new
      medication is first marketed, it is essential to continue the collection and
      monitoring of safety data about adverse drug reactions (ADRs) during the
      medication's life cycle. This activity, known as pharmacovigilance (PV), is
      performed worldwide by the pharmaceutical industry as well as by regulatory
      agencies. In 2012, the Israeli Ministry of Health (MOH) established a
      Pharmacovigilance and Drug Information Department. The Department is tasked with
      identifying, monitoring, and initiating activities aimed at minimizing risks
      associated with medication utilization. To enable this, the MOH has devised
      procedures for PV and promoted extensive legislation in this area that require
      marketing authorization holders (MAHs) and medical institutions in Israel to
      report ADRs and new safety information to the MOH. A computerized database was
      created to support the reporting process. The objective of this article is to
      characterize the PV tools and activities implemented in Israel. METHODS: Since
      September 2014, The Israeli Pharmacovigilance and Drug Information Department
      receives ICSRs at a central computerized database developed for this purpose. The
      data were analyzed by Department personnel and ICSRs were characterized according
      to their seriousness, source, categories of drugs involved, and the reporting
      format. Additionally, the Department reviewed signals detected from ADR reports
      and from other sources and assessed the resulting regulatory actions. RESULTS: An
      analysis of the Individual Case Safety Reports (ICSRs) submitted to the MOH's
      ADRs central database reveals that during the review period, a total of 16,409
      ICSRs were received by the Department and 850 signals were identified, resulting
      in the following PV activities: inquiry and enhanced follow-up (430, 50.6%),
      prescriber's and patient's leaflets updates (204, 24%), recall of
      products/batches (6, 0.7%), alerts for health care professionals (63, 7.4%).
      Eighty five (10%) of the signals required a comprehensive investigation involving
      external specialist and 1 (0.1%) resulted in initiation of epidemiologic study.
      Additionally, in 2015 the Department incorporated comprehensive framework for
      risk minimization of marketed medicinal products, also known as risk management
      plans (RMPs). CONCLUSIONS: As practiced by other health authorities, the Israeli
      MOH effectively implemented various PV tools to ensure the safety of the Israeli
      health consumer.

PMID- 28760140
TI  - The three-dimensional genome organization of Drosophila melanogaster through data
      integration.
AB  - BACKGROUND: Genome structures are dynamic and non-randomly organized in the
      nucleus of higher eukaryotes. To maximize the accuracy and coverage of three
      dimensional genome structural models, it is important to integrate all available
      sources of experimental information about a genome's organization. It remains a
      major challenge to integrate such data from various complementary experimental
      methods. Here, we present an approach for data integration to determine a
      population of complete three-dimensional genome structures that are statistically
      consistent with data from both genome-wide chromosome conformation capture (Hi-C)
      and lamina-DamID experiments. RESULTS: Our structures resolve the genome at the
      resolution of topological domains, and reproduce simultaneously both sets of
      experimental data. Importantly, this data deconvolution framework allows for
      structural heterogeneity between cells, and hence accounts for the expected
      plasticity of genome structures. As a case study we choose Drosophila
      melanogaster embryonic cells, for which both data types are available. Our three
      dimensional genome structures have strong predictive power for structural
      features not directly visible in the initial data sets, and reproduce
      experimental hallmarks of the D. melanogaster genome organization from
      independent and our own imaging experiments. Also they reveal a number of new
      insights about genome organization and its functional relevance, including the
      preferred locations of heterochromatic satellites of different chromosomes, and
      observations about homologous pairing that cannot be directly observed in the
      original Hi-C or lamina-DamID data. CONCLUSIONS: Our approach allows systematic
      integration of Hi-C and lamina-DamID data for complete three-dimensional genome
      structure calculation, while also explicitly considering genome structural
      variability.

PMID- 28760144
TI  - Poultry red mite (Dermanyssus gallinae) infestation: a broad impact
      parasitological disease that still remains a significant challenge for the egg
      laying industry in Europe.
AB  - The poultry red mite, Dermanyssus gallinae, has been described for decades as a
      threat to the egg production industry, posing serious animal health and welfare
      concerns, adversely affecting productivity, and impacting public health. Research
      activities dedicated to controlling this parasite have increased significantly.
      Their veterinary and human medical impact, more particularly their role as a
      disease vector, is better understood. Nevertheless, red mite infestation remains
      a serious concern, particularly in Europe, where the prevalence of red mites is
      expected to increase, as a result of recent hen husbandry legislation changes,
      increased acaricide resistance, climate warming, and the lack of a sustainable
      approach to control infestations. The main objective of the current work was to
      review the factors contributing to this growing threat and to discuss their
      recent development in Europe. We conclude that effective and sustainable
      treatment approach to control poultry red mite infestation is urgently required,
      included integrated pest management.

PMID- 28760143
TI  - Decision support during electronic prescription to stem antibiotic overuse for
      acute respiratory infections: a long-term, quasi-experimental study.
AB  - BACKGROUND: Interventions to support decision-making can reduce inappropriate
      antibiotic use for acute respiratory infections (ARI), but they may not be
      sustainable. The objective of the study is to evaluate the long-term
      effectiveness of a clinical decision-support system (CDSS) interposed at the time
      of electronic (e-) prescriptions for selected antibiotics. METHODS: This is a
      retrospective, observational intervention study, conducted within a large,
      statewide Veterans Affairs health system. Participants are outpatients with an
      initial visit for ARI. A CDSS was deployed upon e-prescription of selected
      antibiotics during the study period. From 01/2004 to 05/2006 (pre-withdrawal
      period), the CDSS targeted azithromycin and the fluoroquinolone gatifloxacin.
      From 05/2006 to 12/2011 (post-withdrawal period), the CDSS was retained for
      azithromycin but withdrawn for the fluoroquinolone. A manual record review was
      conducted to determine concordance of antibiotic prescription with ARI treatment
      guidelines. RESULTS: Of 1131 included ARI visits, 380 (33.6%) were guideline
      concordant. For azithromycin, concordance did not change between the pre- and
      post-withdrawal periods, and adjusted odds of concordance was 8.8 for the full
      study period, compared to unrestricted antibiotics. For fluoroquinolones,
      guideline concordance decreased from 88.6% (39 of 44 visits) to 51.3% (59 of 115
      visits), pre- vs. post-withdrawal periods (p < 0.005). The adjusted odds of
      concordance compared to "All Other Antibiotics" visits decreased from 24.4 (95%
      CI 9.0-66.3) pre-withdrawal to 5.5 (95% CI 3.5-8.8) post-withdrawal (p = .008).
      Concordance did not change between those same time periods for antibiotics that
      were never subjected to the intervention ("All Other Antibiotics"). CONCLUSIONS:
      A CDSS interposed at the time of e-prescription of selected antibiotics can shift
      their use toward ARI treatment guidelines, and this effect can be maintained over
      the long term as long as the CDSS remains in place. Removal of the CDSS after 3.5
      years of implementation resulted in a rise in guideline-discordant antibiotic
      use.

PMID- 28760142
TI  - The renin-angiotensin system: a possible new target for depression.
AB  - Depression remains a debilitating condition with an uncertain aetiology.
      Recently, attention has been given to the renin-angiotensin system. In the
      central nervous system, angiotensin II may be important in multiple pathways
      related to neurodevelopment and regulation of the stress response. Studies of
      drugs targeting the renin-angiotensin system have yielded promising results.
      Here, we review the potential beneficial effects of angiotensin blockers in
      depression and their mechanisms of action. Drugs blocking the angiotensin system
      have efficacy in several animal models of depression. While no randomised
      clinical trials were found, case reports and observational studies showed that
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had
      positive effects on depression, whereas other antihypertensive agents did not.
      Drugs targeting the renin-angiotensin system act on inflammatory pathways
      implicated in depression. Both preclinical and clinical data suggest that these
      drugs possess antidepressant properties. In light of these results, angiotensin
      system-blocking agents offer new horizons in mood disorder treatment.

PMID- 28760145
TI  - Molecular epidemiology of blastocystosis in Malaysia: does seasonal variation
      play an important role in determining the distribution and risk factors of
      Blastocystis subtype infections in the Aboriginal community?
AB  - BACKGROUND: Alternating wet and dry seasons may play an important role in the
      acquisition and distribution of Blastocystis subtype infection in the tropics.
      This cross-sectional study was therefore conducted to provide the prevalence of
      Blastocystis and to determine the potential risk factors associated with each
      subtype during the wet and dry seasons in the Aboriginal community, Pahang,
      Malaysia. METHODS: A total of 473 faecal samples were collected: 256 (54.1%) and
      217 (45.9%) samples were obtained during the wet (October-November 2014) and the
      dry season (June 2015), respectively. All fresh faecal samples were subjected to
      molecular analysis for subtype and allele identification. RESULTS: Of the 473
      samples, 42.6% and 37.8% were positive for Blastocystis ST1, ST2, ST3 and ST4
      during wet and dry seasons, respectively. Prevalence of Blastocystis ST1 was
      significantly higher during the wet season compared to the dry season (Z = 2.146,
      P < 0.05). Analysis of the association of each Blastocystis subtype with
      socioeconomic characteristics showed the presence of other family members
      infected with Blastocystis ST3 and the use of stored river water for domestic
      activities were the significant risk factors for Blastocystis ST3 infections
      during both seasons. Untreated water supply and low monthly household income
      (less or equal to RM 500) were the other significant risk factors for
      Blastocystis ST3 infections during wet and dry season, respectively. The presence
      of other family members with Blastocystis ST1 and ST2 was the only significant
      risk factor associated with ST1 and ST2 infections during both seasons. We
      hypothesise that transmission of Blastocystis ST1, ST2 and ST3 occurred from
      person to person during both seasons. The waterborne transmission was also
      identified as a mode of transmission of Blastocystis ST3. CONCLUSION: The
      significant risk factors identified in this study were important in the dynamic
      transmission of Blastocystis infections during both seasons. Provision of treated
      water supply and health education are affirmative actions to be taken to control
      Blastocystis infections in this community.

PMID- 28760146
TI  - Developing harm reduction in the context of youth substance use: insights from a
      multi-site qualitative analysis of young people's harm minimization strategies.
AB  - BACKGROUND: Youth substance use programming and educational strategies are
      frequently informed by prevention approaches that emphasize abstinence goals,
      which often do not resonate with youth in their lack of acknowledgment of young
      people's social context and how young people perceive positive effects of
      substance use. Further, approaches to drug prevention have been critiqued as
      adopting a one-size-fits-all approach and therefore inadequate in addressing
      substance use in the context of population variation and inequities. In response
      to the limitations of current approaches to prevention, programming informed by
      harm reduction principles that aims to minimize harms without requiring
      abstinence is emergent in school settings. However, youth perspectives informing
      harm reduction are limited in both research and program development. METHODS:
      This paper draws on data from the Researching Adolescent Distress and Resilience
      (RADAR) study, which utilized an ethnographic approach to bring youth voice to
      the literature on mental health and substance use. Qualitative data collection
      included individual interviews (n = 86) with young people aged 13-18 across three
      communities-representing urban, suburban, and rural geographies-in British
      Columbia, Canada. A multi-site qualitative analysis of interview data was
      conducted to identify themes across and within each research site. RESULTS:
      Across all three sites, young people's individual experiences of substance use
      were shaped by geographic, socio-cultural, and political contexts, with youth
      describing their use in relation to the nature of substance use in peer groups
      and in the broader community. To manage their own substance use and reduce
      related harms, youth employed a variety of ad hoc harm minimization strategies
      that were reflective of their respective contexts. CONCLUSIONS: The findings from
      this study suggest the importance of harm reduction approaches that are
      contextually relevant and responsive to the lived experiences of youth. Youth
      perspectives in the development of harm reduction programming are needed to
      ensure that approaches are relatable and meaningful to young people, and
      effective for promoting the minimization of substance-related harms.

PMID- 28760147
TI  - The 2016 HIGh Heels: Health effects And psychosexual BenefITS (HIGH HABITS)
      study: systematic review of reviews and additional primary studies.
AB  - BACKGROUND: High-heeled shoes (high heels) are frequently worn by many women and
      form an important part of female gender identity. Issues of explicit and implicit
      compulsion to wear high heels have been noted. Previous studies and reviews have
      provided evidence that high heels are detrimental to health. However, the
      evidence base remains fragmented and no review has covered both the
      epidemiological and biomechanical literature. In addition, no review has
      considered the psychosexual benefits that offer essential context in
      understanding the public health challenge of high heels. METHODS: We searched
      seven major bibliographic databases up to November 2016, in addition to
      supplementary searches. We initially identified all review articles of any design
      that assessed either the psychosexual benefits or negative musculoskeletal health
      effects of high heels, the latter looking at both the epidemiological and
      biomechanical perspectives. We additionally considered additional primary studies
      on areas that had not been reviewed before or in which a marked lack of evidence
      had been noted. Data were extracted onto standardised forms. Proportionate second
      review was conducted. RESULTS: A total of 506 unique records were identified, 27
      full-text publications were screened and 20 publications (7 reviews and 13
      additional studies) were included in our evidence synthesis. The most up-to-date
      epidemiological review provides clear evidence of an association between high
      heel wear and hallux valgus, musculoskeletal pain and first-party injury. The
      body of biomechanical reviews provides clear evidence of changes indicative of
      increased risk of these outcomes, as well as osteoarthritis, which is not yet
      evidenced by epidemiological studies. There were no reviews on psychosexual
      benefits, but all five identified original studies provided evidence of increased
      attractiveness and/or an impact on men's behaviour associated with high heel
      wear. With regard to second-party injury, evidence is limited to one descriptive
      study and eight case reports. CONCLUSIONS: Our evidence synthesis clearly shows
      that high heels bring psychosexual benefits to women but are detrimental to their
      health. In light of this dilemma, it is important that women's freedom of choice
      is respected and that any remaining issues of explicit or implicit compulsion are
      addressed.

PMID- 28760148
TI  - Does attending an exercise class with a spouse improve long-term exercise
      adherence among people aged 65 years and older: a 6-month prospective follow-up
      study.
AB  - BACKGROUND: Family support can help older adults better adhere to exercise
      routine, but it remains unclear whether an exercise program targeting older
      married couples would have stronger effects on exercise adherence than would a
      program for individuals. The purpose of this study was to determine the effects
      of an exercise program on the exercise adherence of older married couples over a
      24-week follow-up period. METHODS: Thirty-four older married couples and 59 older
      adults participated in this study as couple and non-couple groups (CG and NCG,
      respectively). All participants attended an 8-week supervised program (once a
      week and a home-based exercise program comprising walking and strength exercises)
      and then participated in a follow-up measurement (24 weeks after post
      intervention measurement). Exercise adherence was prospectively measured via an
      exercise habituation diary during the follow-up period-specifically, we asked
      them to record practice rates for walking (>=2 days/week) and strength exercises
      (>=6 items for 2 days/week). A multivariate logistic regression analysis was
      conducted to obtain the CG's odds ratios (ORs) and 95% confidence intervals (CIs)
      for adherence to walking and strength exercise adjusted for potential confounders
      (with NCG as the reference). RESULTS: Although the adherence rate of walking
      exercise in the CG was significantly higher than that in the NCG (29.2%; P <
      0.001), there was no significant difference in the adherence rate of strength
      exercise between the two groups (P = 0.199). The multivariate logistic regression
      analysis showed that CG had significantly higher odds of adherence to walking
      exercise compared with the NCG (3.68 [1.57-8.60]). However, the odds of adherence
      to strength exercise did not significantly differ between the two groups (1.30
      [0.52-3.26]). CONCLUSIONS: These results suggest that an exercise program
      targeting older married couples may be a useful strategy for maintaining walking
      adherence, even six months after the supervised program has ceased. A blinded
      randomized controlled trial will be needed to confirm this conclusion. TRIAL
      REGISTRATION: Retrospectively registered. UMIN Clinical Trials Registry
      (Registered: 02/11/16) UMIN000024689 .

PMID- 28760149
TI  - Collaborative goal setting with elderly patients with chronic disease or
      multimorbidity: a systematic review.
AB  - BACKGROUND: It is challenging to use shared decision-making with patients who
      have a chronic health condition or, especially, multimorbidity. A patient-goal
      oriented approach can thus be beneficial. This study aims to identify and
      evaluate studies on the effects of interventions that support collaborative goal
      setting or health priority setting compared to usual care for elderly people with
      a chronic health condition or multimorbidity. METHODS: This systematic review was
      based on EPOC, PRISMA and MOOSE guidelines. Pubmed, PsychInfo, CINAHL, Web of
      Science, Embase and the Cochrane Central Register of Controlled Trials were
      searched systematically. The following eligibility criteria were applied: 1.
      Randomised (cluster) controlled trials, non-randomised controlled trials,
      controlled before-after studies, interrupted time series or repeated measures
      study design; 2. Single intervention directed specifically at collaborative goal
      setting or health priority setting or a multifactorial intervention including
      these elements; 3. Study population of patients with multimorbidity or at least
      one chronic disease (mean age +/- standard deviation (SD) incl. age 65). 4.
      Studies reporting on outcome measures reducible to outcomes for collaborative
      goal setting or health priority setting. RESULTS: A narrative analysis was
      performed. Eight articles describing five unique interventions, including four
      cluster randomised controlled trials and one randomised controlled trial, were
      identified. Four intervention studies, representing 904, 183, 387 and 1921
      patients respectively, were multifactorial and showed statistically significant
      effects on the application of goal setting (Patient Assessment of Chronic Illness
      Care (PACIC) goal setting subscale), the number of advance directives or the
      inclusion of goals in care plans. Explicit attention for goal setting or priority
      setting by a professional was a common element in these multifactorial
      interventions. One study, which implemented a single-factor intervention on 322
      patients, did not have significant effects on doctor-patient agreement. All the
      studies had methodological concerns in varying degrees. CONCLUSIONS:
      Collaborative goal setting and/or priority setting can probably best be
      integrated in complex care interventions. Further research should determine the
      mix of essential elements in a multifactorial intervention to provide
      recommendations for daily practice. In addition, the necessity of methodological
      innovation and the application of mixed evaluation models must be highlighted to
      deal with the complexity of goal setting and/or priority setting intervention
      studies.

PMID- 28760150
TI  - Bilateral pheochromocytoma with ganglioneuroma component associated with multiple
      neuroendocrine neoplasia type 2A: a case report.
AB  - BACKGROUND: Composite pheochromocytoma/paragangliomas are very rare tumors
      composed of ordinary pheochromocytoma paragangliomas associated with neurogenic
      tumors. Several hereditary susceptibility disorders are known to be associated
      with pheochromocytoma/paragangliomas such as multiple endocrine neoplasia type 2
      (2A or B). To the best of our knowledge, only four cases of composite
      pheochromocytoma/paragangliomas associated with multiple endocrine neoplasia type
      2 have been reported. CASE PRESENTATION: A 40-year-old Arabic woman presented
      with headache, palpitations, paroxysmal hypertension, and weight loss, which she
      had had for the last 3 years. She had a familial history of diabetes and multiple
      endocrine neoplasia type 2. A radiological examination revealed thyroid lesions
      and bilateral adrenal medulla tumors. Our patient had undergone bilateral
      adrenalectomy, total thyroidectomy with cervical lymphadenectomy, and
      parathyroidectomy. A pathological examination confirmed the multiple endocrine
      neoplasia type 2A consisting of left medullary pheochromocytoma, right medullary
      composite pheochromocytoma-ganglioneuroma, medullary carcinoma of the thyroid
      with lymph node metastasis and parathyroid hyperplasia. A genetic analysis also
      revealed that our patient had a RET germline mutation. CONCLUSION: Composite
      pheochromocytoma/paraganglioma associated with multiple endocrine neoplasia type
      2 is a very rare occurrence, as the current literature provides only a few cases.
      Further reported cases are needed in order to understand the behavior and the
      pathogenesis of this uncommon entity.

PMID- 28760151
TI  - PUREAIR protocol: randomized controlled trial of intensive pulmonary
      rehabilitation versus standard care in patients undergoing surgical resection for
      lung cancer.
AB  - BACKGROUND: Non-small cell lung cancer is the most common type of lung cancer.
      Surgery is proven to be the most effective treatment in early stages, despite its
      potential impact on quality of life. Pulmonary rehabilitation, either before or
      after surgery, is associated with reduced morbidity related symptoms and improved
      exercise capacity, lung function and quality of life. METHODS: We describe the
      study protocol for the open-label randomized controlled trial we are conducting
      on patients affected by primary lung cancer (stages I-II) eligible for surgical
      treatment. The control group receives standard care consisting in one educational
      session before surgery and early inpatient postoperative physiotherapy. The
      treatment group receives, in addition to standard care, intensive rehabilitation
      involving 14 preoperative sessions (6 outpatient and 8 home-based) and 39
      postoperative sessions (15 outpatient and 24 home-based) with aerobic, resistance
      and respiratory training, as well as scar massage and group bodyweight exercise
      training. Assessments are performed at baseline, the day before surgery and one
      month and six months after surgery. The main outcome is the long-term exercise
      capacity measured with the Six-Minute Walk Test; short-term exercise capacity,
      lung function, postoperative morbidity, length of hospital stay, quality of life
      (Short Form 12), mood disturbances (Hospital Anxiety and Depression Scale) and
      pain (Numeric Rating Scale) are also recorded and analysed. Patient compliance
      and treatment-related side effects are also collected. Statistical analyses will
      be performed according to the intention-to-treat approach. T-test for independent
      samples will be used for continuous variables after assessment of normality of
      distribution. Chi-square test will be used for categorical variables. Expecting a
      10% dropout rate, assuming alpha of 5% and power of 80%, we planned to enrol 140
      patients to demonstrate a statistically significant difference of 25 m at Six
      Minute Walk Test. DISCUSSION: Pulmonary Resection and Intensive Rehabilitation
      study (PuReAIR) will contribute significantly in investigating the effects of
      perioperative rehabilitation on exercise capacity, symptoms, lung function and
      long-term outcomes in surgically treated lung cancer patients. This study
      protocol will facilitate interpretation of future results and wide application of
      evidence-based practice. TRIAL REGISTRATION: ClinicalTrials.gov Registry n.
      NCT02405273 [31.03.2015].

PMID- 28760153
TI  - An overview of forensic drug testing methods and their suitability for harm
      reduction point-of-care services.
AB  - Given the current opioid crisis around the world, harm reduction agencies are
      seeking to help people who use drugs to do so more safely. Many harm reduction
      agencies are exploring techniques to test illicit drugs to identify and, where
      possible, quantify their constituents allowing their users to make informed
      decisions. While these technologies have been used for years in Europe (Nightlife
      Empowerment & Well-being Implementation Project, Drug Checking Service: Good
      Practice Standards; Trans European Drugs Information (TEDI) Workgroup, Factsheet
      on Drug Checking in Europe, 2011; European Monitoring Centre for Drugs and Drug
      Addiction, An Inventory of On-site Pill-Testing Interventions in the EU: Fact
      Files, 2001), they are only now starting to be utilized in this context in North
      America. The goal of this paper is to describe the most common methods for
      testing illicit substances and then, based on this broad, encompassing review,
      recommend the most appropriate methods for testing at point of care.Based on our
      review, the best methods for point-of-care drug testing are handheld infrared
      spectroscopy, Raman spectroscopy, and ion mobility spectrometry; mass
      spectrometry is the current gold standard in forensic drug analysis. It would be
      prudent for agencies or clinics that can obtain the funding to contact the
      companies who produce these devices to discuss possible usage in a harm reduction
      setting. Lower tech options, such as spot/color tests and immunoassays, are
      limited in their use but affordable and easy to use.

PMID- 28760152
TI  - Randomized controlled trial of S-1 maintenance therapy in metastatic
      esophagogastric cancer - the multinational MATEO study.
AB  - BACKGROUND: The optimal duration of firstline chemotherapy in metastatic
      esophagogastric cancer is unknown. In most clinical trials therapy was given
      until tumour progression or limiting toxicity. Maintenance concepts aiming to
      prolong the duration of response and maintain quality of life have been
      established in other tumour types but not in esophagogastric cancer. S-1 is an
      oral fluoropyrimidine with proven efficacy in metastatic esophagogastric cancer.
      METHODS: The Maintenance Teysuno(r) (S-1) in esophagogastric cancer (MATEO) trial
      is a multinational, randomized phase II study that explores the role of S-1
      maintenance therapy in Her-2 negative, advanced esophagogastric adenocarcinoma.
      After a 12-week firstline platinum-fluoropyrimidine-based chemotherapy patients
      without tumour progression are randomized in a 2:1 allocation to receive S-1
      alone or continue with the same regimen as during the primary period. The primary
      endpoint is overall survival. Secondary endpoints include safety and toxicity,
      progression-free survival and quality of life. Correlative biomarker analyses
      focus on the identification of a subgroup of patients with a prolonged benefit
      from S-1 based maintenance therapy. DISCUSSION: MATEO will be the first trial to
      define the role of a S-1 based maintenance therapy in patients having received a
      platinum-based firstline chemotherapy. TRIAL REGISTRATION: NCT02128243 (date of
      registration: 29-04-2014).

PMID- 28760154
TI  - Dementia knowledge assessment scale (DKAS): confirmatory factor analysis and
      comparative subscale scores among an international cohort.
AB  - BACKGROUND: Dementia is a life-limiting condition that is increasing in global
      prevalence in line with population ageing. In this context, it is necessary to
      accurately measure dementia knowledge across a spectrum of health professional
      and lay populations with the aim of informing targeted educational interventions
      and improving literacy, care, and support. Building on prior exploratory
      analysis, which informed the development of the preliminarily valid and reliable
      version of the Dementia Knowledge Assessment Scale (DKAS), a Confirmatory Factor
      Analysis (CFA) was performed to affirm construct validity and proposed subscales
      to further increase the measure's utility for academics and educators. METHODS: A
      large, de novo sample of 3649 volunteer respondents to a dementia-related online
      course was recruited to evaluate the performance of the DKAS and its proposed
      subscales. Respondents represented diverse cohorts, including health
      professionals, students, and members of the general public. Analyses included CFA
      (using structural equation modelling), measures of internal consistency (alpha),
      and non-parametric tests of subscale correlation (Spearman Correlation) and score
      differences between cohorts (Kruskal-Wallis one-way analysis of variance).
      RESULTS: Findings of the CFA supported a 25-item, four-factor model for the DKAS
      with two items removed due to poor performance and one item moved between
      factors. The resultant model exhibited good reliability (alpha = .85; omega h  =
      .87; overall scale), with acceptable subscale internal consistency (alpha >= .65;
      subscales). Subscales showed acceptable correlation without any indication of
      redundancy. Finally, total and DKAS subscale scores showed good discrimination
      between cohorts of respondents who would be anticipated to hold different levels
      of knowledge on the basis of education or experience related to dementia.
      CONCLUSION: The DKAS has been confirmed as a reliable and valid measure of
      dementia knowledge for diverse populations that is capable of elucidating
      knowledge characteristics across four coherent domains: 1) Causes and
      Characteristics, 2) Communication and Behaviour, 3) Care Considerations, and 4)
      Risks and Health Promotion. Importantly, the four confirmed subscales clearly
      distinguish between groups who might be expected to hold differing levels of
      knowledge about dementia, allowing for a fine-grained level of detail to be
      established when evaluating baseline understanding or knowledge change associated
      with educational intervention.

PMID- 28760155
TI  - Wine glass size and wine sales: a replication study in two bars.
AB  - OBJECTIVE: Wine glass size may influence perceived volume and subsequently
      purchasing and consumption. Using a larger glass to serve the same portions of
      wine was found to increase wine sales by 9.4% (95% CI 1.9, 17.5) in a recent
      study conducted in one bar. The current study aimed to replicate this previous
      work in two other bars using a wider range of glass sizes. To match the previous
      study, a repeated multiple treatment reversal design, during which wine was
      served in glasses of the same design but different sizes, was used. The study was
      conducted in two bars in Cambridge, England, using glass sizes of 300, 370, 510
      ml (Bar 1) and 300 and 510 ml (Bar 2). Customers purchased their choice of a 750
      ml bottle, or standard UK measures of 125, 175 or 250 ml of wine, each of which
      was served with the same glass. RESULTS: Bar 1: Daily wine volume (ml) purchased
      was 10.5% (95% CI 1.0, 20.9) higher when sold in 510 ml compared to 370 ml
      glasses; but sales were not significantly different with 300 ml vs. 370 ml
      glasses (6.5%, 95% CI -5.2, 19.6) [corrected]. Bar 2 Findings were inconclusive
      as to whether daily wine purchased differed when using 510 ml versus 300 ml
      glasses (-1.1%, 95% CI -12.6, 11.9). These results provide a partial replication
      of previous work showing that introducing larger glasses (without manipulating
      portion size) increases purchasing. Understanding the mechanisms by which wine
      glass size influences consumption may elucidate when the effect can be expected
      and when not. Trial registration This study is a replication study, based on the
      procedure set out in the trial registration for the study that it attempts to
      replicate (ISRCTN registry: ISRCTN12018175).

PMID- 28760156
TI  - Predictors of self-reported health among the elderly in Ghana: a cross sectional
      study.
AB  - BACKGROUND: Self-reported health is a widely used measure of health status across
      individuals. As the ageing population increases, the health of the elderly also
      becomes of growing concern. The elderly go through life facing social, economic
      and financial hardships. These hardships are known to affect the health status of
      people as they age. The purpose of this study is to assess social and health
      related factors of self-reported health among the elderly in Ghana. METHODS: A
      multivariate regression analysis in form of a binary and ordinal logistic
      regression were used to determine the association between socioeconomic,
      demographic and health related factors, on self-reported health. The data used
      for this study was drawn from the World Health Organization (WHO) Study on Global
      Ageing and Adult Health (SAGE) Wave 1. RESULTS: In total, out of 2613 respondent,
      579 (20.1%) rated their health status as poor and 2034 (79.9%) as good. The
      results showed that the odds of reporting poor health was 2.5 times higher among
      the old-old compared to the young old. The elderly with one or more than one
      chronic condition had the odds of 1.6 times and 2 times respectively, of
      reporting poor health. Engaging in mild to moderate exercise increased the
      chances of reporting poor health by 1.8 times. The elderly who had never worked
      in a lifetime were 2 times more likely to report poor health. In the same way,
      residents of Eastern and Western parts of Ghana were 2 times more likely to
      report poor health compared to those in the Upper West region. Respondents with
      functional limitations and disabilities were 3.6 times and 2.4 times
      respectively, more likely to report poor health. On the other hand, the odds of
      reporting poor health was 29, 36 and 27% less among respondents in the highest
      income quintiles, former users of tobacco and those satisfied with certain
      aspects of life respectively. Also, current alcohol users were 41% less likely to
      report poor health. CONCLUSION: The health status of the elderly is to an extent
      determined by the circumstances in which they are born, grow and live. The
      findings suggest that addressing social issues faced by individuals in youthful
      age will go a long way to achieving good health in the future. People with
      physical limitations and disabilities are most vulnerable to unmet healthcare
      needs and support system from government, policy makers and family.

PMID- 28760157
TI  - Factors associated with consumption of alcohol in older adults - a comparison
      between two cultures, China and Norway: the CLHLS and the HUNT-study.
AB  - BACKGROUND: There is little knowledge about the consumption of alcohol among
      Chinese and Norwegian older adults aged 65 years and over. The aim of this study
      was to investigate the prevalence and factors related to alcohol consumption
      among older adults in China and Norway. METHODS: The Chinese Longitudinal Healthy
      Longevity Survey (CLHLS) data in 2008-2009 conducted in China and The Nord
      Trondelag Health Study data in 2006-2008 (HUNT3) conducted in Norway were used.
      Mulitvariable logistic regression was used to test the factors related to alcohol
      consumption. RESULTS: The prevalence of participants who drink alcohol in the
      Chinese and Norwegian sample were 19.88% and 46.2%, respectively. The weighted
      prevalence of participants with consumption of alcohol in the Chinese sample of
      women and men were 7.20% and 34.14%, respectively. In the Norwegian sample, the
      prevalence of consumption of alcohol were 43.31% and 65.35% for women and men,
      respectively. Factors such as younger age, higher level of education, living in
      urban areas, living with spouse or partner, and better health status were related
      to higher likelihood of alcohol consumption among Norwegian older women and men;
      while reported better health status and poorer life satisfaction were related to
      higher likelihood of alcohol consumption among Chinese. In addition, rural males
      and older females with higher level of education were more likely to consume
      alcohol. CONCLUSION: The alcohol consumption patterns were quite different
      between China and Norway. Besides economic development levels and cultures in the
      two different countries, demographic characteristics, socioeconomic status,
      overall health status, and life satisfaction were associated with alcohol
      consumption as well.

PMID- 28760158
TI  - Comparative evaluation of a rapid diagnostic test, an antibody ELISA, and a pLDH
      ELISA in detecting asymptomatic malaria parasitaemia in blood donors in Buea,
      Cameroon.
AB  - BACKGROUND: In malaria endemic areas, infected blood donors serve as a source of
      infection to blood recipients, which may adversely affect their prognosis. This
      necessitates the proper screening of blood to be used for transfusion in these
      areas. The purpose of this study was to determine the prevalence of malaria
      parasitaemia in blood donors in Buea, Cameroon, and to evaluate the performance
      of a rapid diagnostic test (RDT), a malaria antibody enzyme-linked immunosorbent
      assay (ELISA), and a Plasmodium lactate dehydrogenase (pLDH) ELISA in the
      detection of asymptomatic malaria parasitaemia in the target population. METHODS:
      In a prospective study conducted between September 2015 and June 2016, 1 240
      potential blood donors were enrolled. The donors were screened for malaria
      parasites using Giemsa microscopy (GM) and a RDT. A sub-sample of 184 samples,
      comprising 88 positive and 96 negative samples, were selected for the evaluation
      of the pLDH ELISA and the antibody ELISA. The chi-square test and correlation
      analysis were performed as part of the statistical analyses. The statistical
      significance cut-off was set at P < 0.05. RESULTS: The prevalence of malaria
      parasitaemia in this study was found to be 8.1% (95% CI: 6.6 - 9.7). The
      prevalence was not observed to be dependent on the age or sex of the
      participants. The RDT had a sensitivity (88.0%), specificity (99.1%), and
      negative predictive value (99.0%) higher than the ELISAs. The performance of the
      pLDH ELISA, which demonstrated the highest positive predictive value (91.6%), was
      generally comparable to the RDT. The sensitivity was lowest with the antibody
      ELISA (69.9%), which also demonstrated the highest false positive and false
      negative rates. The detection threshold for the pLDH (three parasites/MUl) was
      lower compared to the RDT (50 - 60 parasites/MUl). Non-significant positive
      correlations were observed between the parasite density and the pLDH titers and
      malaria antibody titers. CONCLUSIONS: Overall, the RDT and the pLDH ELISA
      demonstrated a perfectly correlated agreement with GM, meanwhile the antibody
      ELISA demonstrated a substantially correlated agreement with GM. The pLDH is
      therefore recommended for mass screening of blood (to detect malaria
      parasitaemia) for transfusions in the study area. However, where this is not
      feasible, an RDT will suffice.

PMID- 28760160
TI  - Regional variations in mortality and causes of death in Israel, 2009-2013.
AB  - BACKGROUND: Regional variations in mortality can be used to study and assess
      differences in disease prevalence and factors leading to disease and mortality
      from different causes. To enable this comparison, it is important to standardize
      the mortality data to adjust for the effects of regional population differences
      in age, nationality and country of origin. METHODS: Standardized mortality ratios
      (SMR) were calculated for the districts and sub-districts in Israel, for total
      mortality by gender as well as for leading causes of death and selected specific
      causes. Correlations were assessed between these SMRs, regional disease risk
      factors and socio-economic characteristics. Implications for health policy were
      then examined. RESULTS: Total mortality in the Northern District of Israel was
      not significantly different from the national average; but the Haifa, Tel Aviv,
      and Southern districts were significantly higher and the Jerusalem, Central,
      Judea and Samaria districts were lower. Cancer SMR was significantly lower in
      Jerusalem and not significantly higher in any region. Heart disease and diabetes
      SMRs were significantly higher in many sub-districts in the north of the country
      and lower in the south. SMRs for septicemia, influenza/pneumonia, and for
      cerebrovascular disease were higher in the south. Septicemia was also
      significantly higher in Tel Aviv and lower in the North, Haifa and Jerusalem
      districts. SMRs for accidents, particularly for motor vehicle accidents were
      significantly higher in the peripheral Zefat and Be'er Sheva sub-districts.
      CONCLUSION: The SMR, adjusted for age and ethnicity, is a good method for
      identifying districts that differ significantly from the national average. Some
      of the regional differences may be attributed to differences in the completion of
      death certificates. This needs to be addressed by efforts to improve reporting of
      causes of death, by educating physicians. The relatively low differences found
      after adjustment, show that factors associated with ethnicity may affect
      mortality more than regional factors. Recommendations include encouraging good
      eating habits, exercise, cancer screening, control of hypertension, reduction of
      smoking and improving road infrastructure and emergency care access in the
      periphery.

PMID- 28760159
TI  - Generation and characterization of new monoclonal antibodies targeting the PHF1
      and AT8 epitopes on human tau.
AB  - Tauopathies are a group of neurodegenerative disorders, including Alzheimer's
      disease, defined by the presence of brain pathological inclusions comprised of
      abnormally aggregated and highly phosphorylated tau protein. The abundance of
      brain tau aggregates correlates with disease severity and select phospho-tau
      epitopes increase at early stages of disease. We generated and characterized a
      series of novel monoclonal antibodies directed to tau phosphorylated at several
      of these phospho-epitopes, including Ser396/Ser404, Ser404 and Thr205. We also
      generated phosphorylation independent antibodies against amino acid residues 193
      211. We show that most of these antibodies are highly specific for tau and
      strongly recognize pathological inclusions in human brains and in a transgenic
      mouse model of tauopathy. They also reveal epitope-specific differences in the
      biochemical properties of Alzheimer's disease sarkosyl-insoluble tau. These new
      reagents will be useful for investigating the progression of tau pathology and
      further as tools to target the cellular transmission of tau pathology.

PMID- 28760161
TI  - Mutation-induced loss of APP function causes GABAergic depletion in recessive
      familial Alzheimer's disease: analysis of Osaka mutation-knockin mice.
AB  - The E693Delta (Osaka) mutation in APP is linked to familial Alzheimer's disease.
      While this mutation accelerates amyloid beta (Abeta) oligomerization, only
      patient homozygotes suffer from dementia, implying that this mutation is
      recessive and causes loss-of-function of amyloid precursor protein (APP). To
      investigate the recessive trait, we generated a new mouse model by knocking-in
      the Osaka mutation into endogenous mouse APP. The produced homozygous,
      heterozygous, and non-knockin littermates were compared for memory,
      neuropathology, and synaptic plasticity. Homozygotes showed memory impairment at
      4 months, whereas heterozygotes did not, even at 8 months. Immunohistochemical
      and biochemical analyses revealed that only homozygotes displayed intraneuronal
      accumulation of Abeta oligomers at 8 months, followed by abnormal tau
      phosphorylation, synapse loss, glial activation, and neuron loss. These
      pathologies were not observed at younger ages, suggesting that a certain
      mechanism other than Abeta accumulation underlies the memory disturbance at 4
      months. For the electrophysiology studies at 4 months, high-frequency stimulation
      evoked long-term potentiation in all mice in the presence of picrotoxin, but in
      the absence of picrotoxin, such potentiation was observed only in homozygotes,
      suggesting their GABAergic deficit. In support of this, the levels of GABA
      related proteins and the number of dentate GABAergic interneurons were decreased
      in 4-month-old homozygotes. Since APP has been shown to play a role in dentate
      GABAergic synapse formation, the observed GABAergic depletion is likely
      associated with an impairment of the APP function presumably caused by the Osaka
      mutation. Oral administration of diazepam to homozygotes from 6 months improved
      memory at 8 months, and furthermore, prevented Abeta oligomer accumulation,
      indicating that GABAergic deficiency is a cause of memory impairment and also a
      driving force of Abeta accumulation. Our findings suggest that the Osaka mutation
      causes loss of APP function, leading to GABAergic depletion and memory disorder
      when wild-type APP is absent, providing a mechanism of the recessive heredity.

PMID- 28760162
TI  - Producing Cochrane systematic reviews-a qualitative study of current approaches
      and opportunities for innovation and improvement.
AB  - BACKGROUND: Producing high-quality, relevant systematic reviews and keeping them
      up to date is challenging. Cochrane is a leading provider of systematic reviews
      in health. For Cochrane to continue to contribute to improvements in heath,
      Cochrane Reviews must be rigorous, reliable and up to date. We aimed to explore
      existing models of Cochrane Review production and emerging opportunities to
      improve the efficiency and sustainability of these processes. METHODS: To inform
      discussions about how to best achieve this, we conducted 26 interviews and an
      online survey with 106 respondents. RESULTS: Respondents highlighted the
      importance and challenge of creating reliable, timely systematic reviews. They
      described the challenges and opportunities presented by current production
      models, and they shared what they are doing to improve review production. They
      particularly highlighted significant challenges with increasing complexity of
      review methods; difficulty keeping authors on board and on track; and the length
      of time required to complete the process. Strong themes emerged about the roles
      of authors and Review Groups, the central actors in the review production
      process. The results suggest that improvements to Cochrane's systematic review
      production models could come from improving clarity of roles and expectations,
      ensuring continuity and consistency of input, enabling active management of the
      review process, centralising some review production steps; breaking reviews into
      smaller "chunks", and improving approaches to building capacity of and sharing
      information between authors and Review Groups. Respondents noted the important
      role new technologies have to play in enabling these improvements. CONCLUSIONS:
      The findings of this study will inform the development of new Cochrane Review
      production models and may provide valuable data for other systematic review
      producers as they consider how best to produce rigorous, reliable, up-to-date
      reviews.

PMID- 28760164
TI  - Acute Chemical Incidents With Injured First Responders, 2002-2012.
AB  - : IntroductionFirst responders, including firefighters, police officers,
      emergency medical services, and company emergency response team members, have
      dangerous jobs that can bring them in contact with hazardous chemicals among
      other dangers. Limited information is available on responder injuries that occur
      during hazardous chemical incidents. METHODS: We analyzed 2002-2012 data on acute
      chemical incidents with injured responders from 2 Agency for Toxic Substances and
      Disease Registry chemical incident surveillance programs. To learn more about
      such injuries, we performed descriptive analysis and looked for trends. RESULTS:
      The percentage of responders among all injured people in chemical incidents has
      not changed over the years. Firefighters were the most frequently injured group
      of responders, followed by police officers. Respiratory system problems were the
      most often reported injury, and the respiratory irritants, ammonia,
      methamphetamine-related chemicals, and carbon monoxide were the chemicals more
      often associated with injuries. Most of the incidents with responder injuries
      were caused by human error or equipment failure. Firefighters wore personal
      protective equipment (PPE) most frequently and police officers did so rarely.
      Police officers' injuries were mostly associated with exposure to ammonia and
      methamphetamine-related chemicals. Most responders did not receive basic
      awareness-level hazardous material training. CONCLUSION: All responders should
      have at least basic awareness-level hazardous material training to recognize and
      avoid exposure. Research on improving firefighter PPE should continue. (Disaster
      Med Public Health Preparedness. 2018;12:211-221).

PMID- 28760163
TI  - Stable engraftment of human microbiota into mice with a single oral gavage
      following antibiotic conditioning.
AB  - BACKGROUND: Human microbiota-associated (HMA) animal models relying on germ-free
      recipient mice are being used to study the relationship between intestinal
      microbiota and human disease. However, transfer of microbiota into germ-free
      animals also triggers global developmental changes in the recipient intestine,
      which can mask disease-specific attributes of the donor material. Therefore, a
      simple model of replacing microbiota into a developmentally mature intestinal
      environment remains highly desirable. RESULTS: Here we report on the development
      of a sequential, three-course antibiotic conditioning regimen that allows
      sustained engraftment of intestinal microorganisms following a single oral gavage
      with human donor microbiota. SourceTracker, a Bayesian, OTU-based algorithm,
      indicated that 59.3 +/- 3.0% of the fecal bacterial communities in treated mice
      were attributable to the donor source. This overall degree of microbiota
      engraftment was similar in mice conditioned with antibiotics and germ-free mice.
      Limited surveys of systemic and mucosal immune sites did not show evidence of
      immune activation following introduction of human microbiota. CONCLUSIONS: The
      antibiotic treatment protocol described here followed by a single gavage of human
      microbiota may provide a useful, complimentary HMA model to that established in
      germ-free facilities. The model has the potential for further in-depth
      translational investigations of microbiota in a variety of human disease states.

PMID- 28760165
TI  - Diagnostic Imaging in Disasters: A Bibliometric Analysis.
AB  - OBJECTIVE: To investigate the role of diagnostic imaging in the clinical
      diagnosis, treatment, and follow-up management of patients in response to
      disasters. METHODS: A MEDLINE (OVID) search of original research articles
      identified 177 articles on this topic published since 2000. A bibliometric
      analysis was conducted on the top 100 articles ranked by average yearly citation.
      RESULTS: The most frequently studied disaster categories were disease outbreak
      (55 articles), armed conflict (23 articles), terrorist incident (10 articles),
      and earthquake (7 articles). The most studied disasters were the H1N1 influenza
      outbreak in 2009 (28 articles), Severe Acute Respiratory Syndrome outbreak in
      2003 (24 articles), War in Afghanistan, 2001-2014 (8 articles), Iraq War, 2003
      2011 (6 articles), and the Sichuan earthquake (China) in 2008 (6 articles). Among
      the first authors, 59 were primarily affiliated with Radiology. The United States
      of America produced the most articles (25 articles), followed by the People's
      Republic of China (24 articles). Eighty-one studies were retrospective, with 19
      studies being prospective. Computed tomography was the most investigated modality
      (52.8%), followed by conventional radiography (33.3%) and ultrasound (9.7%).
      CONCLUSIONS: Our study identifies intellectual milestones in the utility of
      diagnostic imaging in response to various disasters, and could help guide future
      research in developing disaster management plans. (Disaster Med Public Health
      Preparedness. 2018;12:265-277).

PMID- 28760166
TI  - Quantifying Network Dynamics and Information Flow Across Chinese Social Media
      During the African Ebola Outbreak.
AB  - OBJECTIVE: Social media provides us with a new platform on which to explore how
      the public responds to disasters and, of particular importance, how they respond
      to the emergence of infectious diseases such as Ebola. Provided it is
      appropriately informed, social media offers a potentially powerful means of
      supporting both early detection and effective containment of communicable
      diseases, which is essential for improving disaster medicine and public health
      preparedness. METHODS: The 2014 West African Ebola outbreak is a particularly
      relevant contemporary case study on account of the large number of annual
      arrivals from Africa, including Chinese employees engaged in projects in Africa.
      Weibo (Weibo Corp, Beijing, China) is China's most popular social media platform,
      with more than 2 billion users and over 300 million daily posts, and offers great
      opportunity to monitor early detection and promotion of public health awareness.
      RESULTS: We present a proof-of-concept study of a subset of Weibo posts during
      the outbreak demonstrating potential and identifying priorities for improving the
      efficacy and accuracy of information dissemination. We quantify the evolution of
      the social network topology within Weibo relating to the efficacy of information
      sharing. CONCLUSIONS: We show how relatively few nodes in the network can have a
      dominant influence over both the quality and quantity of the information shared.
      These findings make an important contribution to disaster medicine and public
      health preparedness from theoretical and methodological perspectives for dealing
      with epidemics. (Disaster Med Public Health Preparedness. 2018;12:26-37).

PMID- 28760167
TI  - Measurement invariance across educational levels and gender in 12-item Zarit
      Burden Interview (ZBI) on caregivers of people with dementia.
AB  - BACKGROUND: The Zarit Burden Interview (ZBI) is a commonly used self-report to
      assess caregiver burden. A 12-item short form of the ZBI has been developed;
      however, its measurement invariance has not been examined across some different
      demographics. It is unclear whether different genders and educational levels of a
      population interpret the ZBI items similarly. Therefore, this study aimed to
      examine the measurement invariance of the 12-item ZBI across gender and
      educational levels in a Taiwanese sample. METHODS: Caregivers who had a family
      member with dementia (n = 270) completed the ZBI through telephone interviews.
      Three confirmatory factor analysis (CFA) models were conducted: Model 1 was the
      configural model, Model 2 constrained all factor loadings, Model 3 constrained
      all factor loadings and item intercepts. Multiple group CFAs and the differential
      item functioning (DIF) contrast under Rasch analyses were used to detect
      measurement invariance across males (n = 100) and females (n = 170) and across
      educational levels of junior high schools and below (n = 86) and senior high
      schools and above (n = 183). RESULTS: The fit index differences between models
      supported the measurement invariance across gender and across educational levels
      (? comparative fit index (CFI) = -0.010 and 0.003; ? root mean square error of
      approximation (RMSEA) = -0.006 to 0.004). No substantial DIF contrast was found
      across gender and educational levels (value = -0.36 to 0.29). CONCLUSIONS: The
      ZBI is appropriate for combined use and for comparisons in caregivers across
      gender and different educational levels in Taiwan.

PMID- 28760168
TI  - The Impact of a Computerized Clinical Decision Support Tool on Inappropriate
      Clostridium difficile Testing.
AB  - OBJECTIVE To evaluate the effectiveness of a computerized clinical decision
      support intervention aimed at reducing inappropriate Clostridium difficile
      testing DESIGN Retrospective cohort study SETTING University of Pennsylvania
      Health System, comprised of 3 large tertiary-care hospitals PATIENTS All adult
      patients admitted over a 2-year period INTERVENTION Providers were required to
      use an order set integrated into a commercial electronic health record to order
      C. difficile toxin testing. The order set identified patients who had received
      laxatives within the previous 36 hours and displayed a message asking providers
      to consider stopping laxatives and reassessing in 24 hours prior to ordering C.
      difficile testing. Providers had the option to continue or discontinue laxatives
      and to proceed with or forgo testing. The primary endpoint was the change in
      inappropriate C. difficile testing, as measured by the number of patients who had
      C. difficile testing ordered while receiving laxatives. RESULTS Compared to the 1
      year baseline period, the intervention resulted in a decrease in the proportion
      of inappropriate C. difficile testing (29.6% vs 27.3%; P=.02). The intervention
      was associated with an increase in the number of patients who had laxatives
      discontinued and did not undergo C. difficile testing (5.8% vs 46.4%; P<.01) and
      who had their laxatives discontinued and underwent testing (5.4% vs 35.2%;
      P<.01). We observed a nonsignificant increase in the proportion of patients with
      C. difficile related complications (5.0% vs 8.9%; P=.11). CONCLUSIONS A C.
      difficile order set was successful in decreasing inappropriate C. difficile
      testing and improving the timely discontinuation of laxatives. Infect Control
      Hosp Epidemiol 2017;38:1204-1208.

PMID- 28760169
TI  - The Importance of Self-Efficacy in Parental Emergency Preparedness: A Moderated
      Mediation Model.
AB  - OBJECTIVE: Disasters occur without warning and can have devastating consequences.
      Emergency preparedness can reduce negative effects. It is especially important
      that parents prepare, as children are particularly vulnerable after disasters.
      This study tested 2 hypotheses: (1) adults with more children are likely to be
      better prepared than those with fewer or no children because greater caretaking
      is linked to greater perceived threat of disaster leading to greater preparedness
      and (2) the strength of this mediational link varies as a function of parental
      self-efficacy. METHODS: Data from an online survey about human-made disasters
      (terrorism) with a community convenience sample were used to test the hypothesis
      that perceived threat mediates the relationship between parental status (number
      of children cared for) and preparedness behaviors, moderated by level of self
      efficacy for emergency preparedness. RESULTS: A bootstrapping analysis with
      relevant covariates supported the hypothesized mediating effect of threat on the
      relationship between parental status and preparedness. This relationship was
      strengthened at higher levels of parental preparedness self-efficacy.
      CONCLUSIONS: The results of this study are particularly relevant for preparedness
      interventions. Because threat leads to preparedness, particularly for parents
      with high self-efficacy, it is important to focus attention on factors that can
      improve parents' sense of self-efficacy. (Disaster Med Public Health
      Preparedness. 2018; 12: 345-351).

PMID- 28760170
TI  - Evaluation of cardiac autonomic function using heart rate variability in children
      with acute carbon monoxide poisoning.
AB  - : Introduction Carbon monoxide poisoning may cause myocardial toxicity and
      cardiac autonomic dysfunction, which may contribute to the development of life
      threatening arrhythmias. We investigated the potential association between acute
      carbon monoxide exposure and cardiac autonomic function measured by heart rate
      variability. METHOD: The present study included 40 children aged 1-17 years who
      were admitted to the Pediatric Intensive Care Unit with acute carbon monoxide
      poisoning and 40 healthy age- and sex-matched controls. Carboxyhaemoglobin and
      cardiac enzymes were measured at admission. Electrocardiography was performed on
      admission and discharge, and 24-hour Holter electrocardiography was digitally
      recorded. Heart rate variability was analysed at both time points - 24-hour
      recordings - and frequency domains - from the first 5 minutes of intensive care
      unit admission. RESULTS: Time domain and frequency indices such as high-frequency
      spectral power and low-frequency spectral power were similar between patient and
      control groups (p>0.05). The ratio of low-frequency spectral power to high
      frequency spectral power was significantly lower in the carbon monoxide poisoning
      group (p<0.001) and was negatively correlated with carboxyhaemoglobin levels (r=
      0.351, p<0.05). The mean heart rate, QT dispersion, corrected QT dispersion, and
      P dispersion values were higher in the carbon monoxide poisoning group (p<0.05)
      on admission. The QT dispersion and corrected QT dispersion remained longer in
      the carbon monoxide poisoning group compared with controls on discharge (p<0.05).
      CONCLUSION: The frequency domain indices, especially the ratio of low-frequency
      spectral power to high-frequency spectral power, are useful for the evaluation of
      the cardiac autonomic function. The decreased low-frequency spectral power-to
      high-frequency spectral power ratio reflects a balance of the autonomic nervous
      system, which shifted to parasympathetic components.

PMID- 28760171
TI  - Utility of Ambulance Data for Real-Time Syndromic Surveillance: A Pilot in the
      West Midlands Region, United Kingdom.
AB  - : Introduction The Public Health England (PHE; United Kingdom) Real-Time
      Syndromic Surveillance Team (ReSST) currently operates four national syndromic
      surveillance systems, including an emergency department system. A system based on
      ambulance data might provide an additional measure of the "severe" end of the
      clinical disease spectrum. This report describes the findings and lessons learned
      from the development and preliminary assessment of a pilot syndromic surveillance
      system using ambulance data from the West Midlands (WM) region in England.
      Hypothesis/Problem Is an Ambulance Data Syndromic Surveillance System (ADSSS)
      feasible and of utility in enhancing the existing suite of PHE syndromic
      surveillance systems? METHODS: An ADSSS was designed, implemented, and a pilot
      conducted from September 1, 2015 through March 1, 2016. Surveillance cases were
      defined as calls to the West Midlands Ambulance Service (WMAS) regarding patients
      who were assigned any of 11 specified chief presenting complaints (CPCs) during
      the pilot period. The WMAS collected anonymized data on cases and transferred the
      dataset daily to ReSST, which contained anonymized information on patients'
      demographics, partial postcode of patients' location, and CPC. The 11 CPCs
      covered a broad range of syndromes. The dataset was analyzed descriptively each
      week to determine trends and key epidemiological characteristics of patients, and
      an automated statistical algorithm was employed daily to detect higher than
      expected number of calls. A preliminary assessment was undertaken to assess the
      feasibility, utility (including quality of key indicators), and timeliness of the
      system for syndromic surveillance purposes. Lessons learned and challenges were
      identified and recorded during the design and implementation of the system.
      RESULTS: The pilot ADSSS collected 207,331 records of individual ambulance calls
      (daily mean=1,133; range=923-1,350). The ADSSS was found to be timely in
      detecting seasonal changes in patterns of respiratory infections and increases in
      case numbers during seasonal events. CONCLUSIONS: Further validation is
      necessary; however, the findings from the assessment of the pilot ADSSS suggest
      that selected, but not all, ambulance indicators appear to have some utility for
      syndromic surveillance purposes in England. There are certain challenges that
      need to be addressed when designing and implementing similar systems. Todkill D ,
      Loveridge P , Elliot AJ , Morbey RA , Edeghere O , Rayment-Bishop T , Rayment
      Bishop C , Thornes JE , Smith G . Utility of ambulance data for real-time
      syndromic surveillance: a pilot in the West Midlands region, United Kingdom.
      Prehosp Disaster Med. 2017;32(6):667-672.

PMID- 28760173
TI  - Geriatric Assessments and Medication Therapy Management Approaches in Elderly
      Oncology Patients.

PMID- 28760172
TI  - Association of Sleep Quality on Memory-Related Executive Functions in Middle Age.
AB  - OBJECTIVES: Sleep quality affects memory and executive function in older adults,
      but little is known about its effects in midlife. If it affects cognition in
      midlife, it may be a modifiable factor for later-life functioning. METHODS: We
      examined the association between sleep quality and cognition in 1220 middle-aged
      male twins (age 51-60 years) from the Vietnam Era Twin Study of Aging. We
      interviewed participants with the Pittsburgh Sleep Quality Index and tested them
      for episodic memory as well as executive functions of inhibitory and interference
      control, updating in working memory, and set shifting. Interference control was
      assessed during episodic memory, inhibitory control during working memory, and
      non-memory conditions and set shifting during working memory and non-memory
      conditions. RESULTS: After adjusting for covariates and correcting for multiple
      comparisons, sleep quality was positively associated with updating in working
      memory, set shifting in the context of working memory, and better visual-spatial
      (but not verbal) episodic memory, and at trend level, with interference control
      in the context of episodic memory. CONCLUSIONS: Sleep quality was associated with
      visual-spatial recall and possible resistance to proactive/retroactive
      interference. It was also associated with updating in working memory and with set
      shifting, but only when working memory demands were relatively high. Thus,
      effects of sleep quality on midlife cognition appear to be at the intersection of
      executive function and memory processes. Subtle deficits in these age-susceptible
      cognitive functions may indicate increased risk for decline in cognitive
      abilities later in life that might be reduced by improved midlife sleep quality.
      (JINS, 2018, 24, 67-76).

PMID- 28760175
TI  - A Randomized Control Intervention Investigating the Effects of Acute Exercise on
      Emotional Regulation.
AB  - OBJECTIVES: Exercise may help to cope with hectic or demanding events after a
      stressful situation occurs. Limited research has evaluated whether exercise,
      prior to a stressor, helps to facilitate subsequent emotional regulation. This
      pilot study addresses this novel paradigm. We employed a randomized controlled
      trial evaluating the effects of acute exercise on emotional regulation. METHODS:
      Participants were randomly assigned to stretch (control group, N = 10), walk (N =
      9), or jog (N = 8) for 15-minutes, after which they were exposed to a film clip
      intended to elicit a negative emotional response. Participants' emotions were
      monitored before and during exercise, as well as after the film clip. Emotional
      responses were evaluated using the Exercise Induced Feeling Inventory and
      Affective Circumplex Scale. RESULTS: A group x time splitplot interaction effect
      was significant for anger (p = .046) and anxiousness (p = .038). Follow-up
      analyses showed that only the stretching group (p = .048) had a significantly
      increased anger score from baseline to post-film clip, suggesting a protective
      emotional effect from walking and jogging. CONCLUSIONS: Exercise was effective in
      regulating anger and anxiousness after a stressful event. These findings provide
      evidence for potential preventive effects of exercise in facilitating emotional
      regulation.

PMID- 28760174
TI  - Utility of Social Cognitive Theory in Intervention Design for Promoting Physical
      Activity among African-American Women: A Qualitative Study.
AB  - OBJECTIVE: We examined the cultural relevance of Social Cognitive Theory (SCT) in
      the design of a physical activity intervention for African-American women.
      METHODS: A qualitative study design was used. Twenty-five African-American women
      (Mean age = 38.5 years, Mean BMI = 39.4 kg.m2) were enrolled in a series of focus
      groups (N = 9) to elucidate how 5 SCT constructs (ie, Behavioral Capability,
      Outcome Expectations, Self-efficacy, Self-regulation, Social Support) can be
      culturally tailored in the design of a physical activity program for African
      American women. RESULTS: For the construct of Behavioral Capability, participants
      were generally unaware of the amount, intensity, and types of physical activity
      needed for health benefits. Outcome Expectations associated with physical
      activity included increased energy, improved health, weight loss, and positive
      role modeling behaviors. Constructs of Self-efficacy and Self-regulation were
      elicited through the women perceiving themselves as a primary barrier to physical
      activity. Participants endorsed the need of a strong social support component and
      identified a variety of acceptable sources to include in a physical activity
      program (ie, family, friends, other program participants). CONCLUSIONS: Findings
      explicate the utility of SCT as a behavioral change theoretical basis for
      tailoring physical activity programs to African-American women.

PMID- 28760176
TI  - Psychometrics Matter in Health Behavior: A Long-term Reliability Generalization
      Study.
AB  - OBJECTIVES: Despite numerous calls for increased understanding and reporting of
      reliability estimates, social science research, including the field of health
      behavior, has been slow to respond and adopt such practices. Therefore, we offer
      a brief overview of reliability and common reporting errors; we then perform
      analyses to examine and demonstrate the variability of reliability estimates by
      sample and over time. METHODS: Using meta-analytic reliability generalization, we
      examined the variability of coefficient alpha scores for a well-designed,
      consistent, nationwide health study, covering a span of nearly 40 years. RESULTS:
      For each year and sample, reliability varied. Furthermore, reliability was
      predicted by a sample characteristic that differed among age groups within each
      administration. CONCLUSIONS: We demonstrated that reliability is influenced by
      the methods and individuals from which a given sample is drawn. Our work echoes
      previous calls that psychometric properties, particularly reliability of scores,
      are important and must be considered and reported before drawing statistical
      conclusions.

PMID- 28760177
TI  - Physical Activity and Diabetes-related Health Beliefs of Marshallese Adults.
AB  - OBJECTIVE: We sought to improve understanding of diabetes-related health beliefs
      and physical activity behaviors of Marshallese adults with and without type 2
      diabetes (T2D). METHODS: We used tests of comparison and regression analyses to
      examine data from 376 Marshallese adults collected at church-based events.
      RESULTS: One in 5 (20.2%) respondents had received a T2D diagnosis. About one
      fourth of the respondents fell into one of 4 physical activity levels: zero times
      per week (28.7%), one time per week (19.4%), 2-3 times per week (24.7%) and >=4
      times per week (26.9%). Using logistic regression, we found T2D diagnosis status
      was not statistically associated with level of physical activity. However, having
      time to be physically active was significantly associated with being physically
      active >=4 times per week. Being obese, having less than a high school education,
      not having time, and not having a comfortable place to exercise were
      significantly associated with never being physically active. CONCLUSIONS: These
      findings help fill gaps in Pacific Islander health literature and will inform
      public health interventions to improve rates of physical activity among the
      Marshallese and other Pacific Islander communities.

PMID- 28760179
TI  - Determinants of Willingness to Accept Secondhand Smoke Exposure.
AB  - OBJECTIVES: In this study, the objective was to assess determinants of
      willingness to accept secondhand smoke (SHS) exposure among dental students.
      METHODS: This cross-sectional study included 420 dental students. Multiple linear
      regression analyses assessed the determinants of willingness to accept SHS
      exposure. RESULTS: A total of 336 students completed questionnaires. The
      multivariate model showed a direct relationship of increased willingness to
      accept SHS exposure with being a smoker (beta = 19.2, 95% confidence interval
      (CI) = 14.2 to 24.1, p < .0001), presence of a smoker in the household (beta =
      10.6, 95% CI = 6.2 to 15.1, p < .0001), presence of a smoker in a
      friends/relatives' house (beta = 8.6, 95% CI = 4.6 to 12.5, p < .0001), and being
      a man (beta = 7.3, 95% CI = 3.1 to 11.5, p = .001). There was an inverse
      relationship with increased knowledge of health risks (beta = -.215, 95% CI = 
      .402 to -.028, p = .025). CONCLUSIONS: The willingness to accept SHS exposure was
      positively associated with the presence of a smoker in the household or in a
      friends/relatives' house, being a smoker, and being a man. Knowledge of health
      risks showed an inverse association.

PMID- 28760178
TI  - Psychosocial Predictors of HBV Screening Behavior among Vietnamese Americans.
AB  - OBJECTIVE: We evaluated the influence of psychosocial factors on HBV screening.
      METHODS: Sample consisted of 1716 Vietnamese participants in our previous HBV
      intervention trial, recruited from 36 community-based organizations in
      Pennsylvania, New Jersey, and New York City between 2009 and 2014. Using the
      Health Belief Model and Social Cognitive Theory, we measured self-efficacy,
      knowledge, perceived barriers, perceived benefits, perceived severity, and risk
      susceptibility. Analysis of covariance was used to compare pre- and post
      intervention changes of psychosocial variables. Structural equation modeling was
      used to explore the direct and indirect effects of the psychosocial variables on
      HBV screening. RESULTS: Knowledge, self-efficacy, perceived benefits, and
      perceived barriers were directly associated with HBV screening; knowledge had the
      strongest effect. Perceived severity and risk susceptibility had indirect
      association with HBV screening through other variables. Indirect paths among the
      6 psychosocial variables were also identified. CONCLUSION: To promote HBV
      screening among Vietnamese Americans, intervention efforts should focus on
      increasing knowledge, self-efficacy, and perceived benefits, decreasing perceived
      barriers, and accounting for the dynamic cognitive processing.

PMID- 28760180
TI  - Tobacco Marketing, E-cigarette Susceptibility, and Perceptions among Adults.
AB  - OBJECTIVE: Understanding the impact of tobacco marketing on e-cigarette (EC)
      susceptibility and perceptions is essential to inform efforts to mitigate tobacco
      product burden on public health. METHODS: Data were collected online in 2016 from
      634 conventional cigarette (CC) smokers and 393 non-smokers using a convenience
      sample from Amazon Mechanical Turk. Logistic regression models, stratified by
      smoking status and adjusted for socio-demographics, examined the relationship
      among tobacco advertisements and coupons, EC and CC susceptibility, and EC
      perceptions. RESULTS: Among non-smokers, increased exposure to tobacco
      advertising and receiving tobacco coupons was significantly related to measures
      of EC and CC susceptibility (p < .05). Older, more educated non-smokers had
      decreased odds of EC susceptibility (p < .05). Additionally, increased exposure
      to tobacco advertising was significantly associated with the perceptions of EC
      not containing nicotine and being less addictive than CC among smokers (p < .05).
      CONCLUSIONS: Increased exposure to tobacco advertising outlets could influence
      future EC and CC use in non-smokers and perceptions in smokers, while receiving
      coupons could affect EC and CC susceptibility among non-smokers. Future research
      is needed to determine whether policies to minimize exposure to tobacco marketing
      reduce EC use by decreasing susceptibility.

PMID- 28760181
TI  - School Physical Activity Programming and Gross Motor Skills in Children.
AB  - OBJECTIVE: We examined the effect of a comprehensive school physical activity
      program (CSPAP) on gross motor skills in children. METHODS: Participants were 959
      children (1st-6th grade; Mean age = 9.1 +/- 1.5 years; 406 girls, 553 boys)
      recruited from 5 low-income schools receiving a year-long CSPAP intervention.
      Data were collected at the beginning of the school year and at a 36-week follow
      up. Gross motor skills were assessed using the Test for Gross Motor Development
      (3rd ed.) (TGMD-3) instrument. Multi-level mixed effects models were employed to
      examine the effect of CSPAP on TGMD-3 scores, testing age and sex as effect
      modifiers and adjusting for clustering of observations within the data structure.
      RESULTS: There were statistically significant coefficients for time (beta = 8.1,
      95% CI [3.9, 12.3], p < .001) and an age * time interaction (beta = -1.7, 95% CI
      [-2.3, -1.1], p < .001) on TGMD-3 total scores. Significant improvements were
      also seen for locomotor skills and ball skills sub-test scores. CONCLUSIONS:
      Children showed improved gross motor skill scores at the end of the 36-week CSPAP
      that were modified by age, as younger children displayed greater improvements in
      TGMD-3 scores compared to older children.

PMID- 28760182
TI  - Body Image Satisfaction as a Physical Activity Indicator in University Students.
AB  - OBJECTIVE: We examined the association of body image satisfaction (BIS) with
      physical activity (PA) in university athletes and non-athletes from northern
      Mexico. METHODS: In a non-probability cross-sectional study, 294 participants
      (51% male, 41% athletes; 18-35 years old) completed 2 self-administered
      questionnaires to evaluate BIS and PA. We categorized somatotypes (endomorphy
      mesomorphy-ectomorphy) by international standardized anthropometry. Data analysis
      included the Mann-Whitney U test, chi2test, Kendall's Tau-b correlation, binary
      logistic regression analysis, and receiver operating characteristic (ROC) curves.
      RESULTS: Self-perceived sports abilities and desirable body shape predicted 30%
      of sports participation in students, whereas an endomorphic shape (<5.4 units)
      and being male predicted 15.4% of sports participation. CONCLUSIONS: BIS was a
      reliable indicator of sports participation among these university students.

PMID- 28760184
TI  - Perceived Influences on Farmers' Market Use among Urban, WIC-enrolled Women.
AB  - OBJECTIVES: We identified perceived barriers and facilitators to purchasing
      fruits and vegetables (FV) at farmers' markets, FV shopping practices, and
      reactions to a planned online lesson to promote farmers' market use among urban,
      inner-city WIC-enrolled women. METHODS: Thirteen focus groups were conducted with
      3-5 participants each (N = 54). RESULTS: Common barriers were structural
      (transportation issues) and informational (not knowing the locations of markets).
      Improving access (by increasing the number of area markets, expanding market
      hours and locations, and increasing transportation options to markets) and
      raising awareness of the importance of eating healthfully were common
      facilitators. Information was sought on the locations of farmers who accept FV
      vouchers provided by WIC, FV sold at farmers' markets, reasons to eat locally
      grown FV, and FV food safety and preparation skills. Questions were raised about
      the accessibility of an online lesson; providing information via inperson
      seminars and handouts also was recommended. Although purchasing FV at
      supermarkets and corner stores and bodegas was common, concerns were expressed
      about the freshness, cost, quality, and variety of produce sold at these venues.
      CONCLUSIONS: Findings aid understanding of factors to consider in designing
      interventions to promote farmers' market use in this population.

PMID- 28760183
TI  - Prevalence and Factors Associated with Smokeless Tobacco Use, 2014-2016.
AB  - OBJECTIVES: We aimed to determine whether the prevalence of current use of
      smokeless tobacco products (STPs) changed during 2014-2016 and examine factors
      associated with use among adults in the United States (US). METHODS: Data were
      obtained from Tobacco Products and Risk Perceptions Surveys of probability
      samples representative of US adults in 2014, 2015, and 2016. Change over time in
      current (past 30 day) STP use was examined using pairwise comparisons of
      proportions and multivariable logistic regression. Associated factors were
      examined using Rao-Scott chi2 and multivariable logistic regression. RESULTS: The
      prevalence of current STP use was higher in 2015 (3.6%) than in 2014 (2.3%, p <
      .001) and 2016 (2.7%, p = .018) among US adults. In 2016, current STP use was
      associated with being male, under age 60, currently using hookah or e-cigarettes,
      and having less than a college degree. Rates of use did not vary by cigarette
      smoking status, race/ethnicity, income, or metropolitan statistical area (MSA).
      CONCLUSIONS: The prevalence of current STP use peaked in 2015. In 2016, current
      STP use was more prevalent among males and adults with lower education.
      Continuous monitoring of STP use is needed, particularly non-cigarette tobacco
      product users.

PMID- 28760185
TI  - Fall-related Comorbidity and Health Beliefs among Cancer Survivors Participating
      in a Community-based Exercise Intervention.
AB  - OBJECTIVES: Health beliefs (HB) and fall and balance-related outcomes were
      examined following a 26-week community-based exercise intervention among cancer
      survivors (CS). METHODS: Fall and balance-related measures and HB were
      quantitatively and qualitatively examined during a 26-week intervention among CS
      (N = 33). Of the 33 participants, 28 consented to an interview about their
      physical activity (PA) behavior. RESULTS: Participants scored high on balance
      efficacy (median +/- range = 8.68 +/- 1.53) and reported high perception of
      having barriers to PA (mean +/- SD = 4.66 +/- 0.59). Fall-related measures
      improved after the 26-week intervention (p = .002). Most cues to action to engage
      in PA were delivered by a healthcare professional (N = 18). Once enrolled in the
      intervention, social benefits and access to a program tailored toward CS emerged
      as motivating factors to engage in PA (N = 12, N = 11, respectively).
      CONCLUSIONS: There is a need to design fall risk reduction programs tailored to
      CS and to offer these programs in an environment that fits the unique physical
      and social needs of CS.

PMID- 28760186
TI  - Immigrant Enclaves and Inadequate Prenatal Care among Mexican-origin Mothers.
AB  - OBJECTIVES: This study is an investigation of the relationships between residing
      in different types of ethnic enclave neighborhoods and inadequate use of prenatal
      care among Mexican-origin mothers. METHODS: A unique dataset was created using
      National Center for Health Statistics 2008 restricted-use detailed natality
      files, the 2005-2009 American Community Survey, and the Department of Health and
      Human Services Area Resource file. Hierarchical modeling was used. RESULTS:
      Mexican-origin mothers' residential contexts are associated with the inadequacy
      of their prenatal care utilization beyond their individual characteristics.
      Specifically, residing in Mexican immigrant enclaves is associated with increased
      odds of having inadequate use of prenatal care. In contrast, residing in other
      types of ethnic enclaves (Mexican/Hispanic ethnic enclaves) and non-Hispanic
      white neighborhoods is associated with decreased odds of having inadequate
      utilization of prenatal care even after the inclusion of contextual-level
      controls for individual characteristics, neighborhood socioeconomic status, and
      the availability of healthcare infrastructure resources. CONCLUSIONS: Residing in
      immigrant enclaves is important for understanding the inadequacy of prenatal care
      utilization for Mexican-origin mothers. These findings have policy implications
      for designing place-based programs to target certain residential contexts where
      women are at greater risk of having inadequate use of prenatal care.

PMID- 28760187
TI  - Demographic Factors Predict Disparities in Number of Assets Youth Possess.
AB  - OBJECTIVES: This study's purpose was to determine if youth race/ethnicity, youth
      age and sex, parent income and education, household wealth, family poverty, and
      family structure were prospectively associated with youth assets in a community
      based sample of racially/ethnically and economically-diverse youth and their
      parents. METHODS: Five waves of data were collected annually (2003 to 2008) from
      youth (N = 1111; Mean age = 14.4 years, SD = 1.6) and their parents using in
      person, computer-assisted interviewing methods. Marginal logistic regression
      models and generalized estimating equations were conducted to assess prospective
      associations between the demographic factors and the number of assets the youth
      possessed (more than or less than the median number of 12 assets). RESULTS:
      Results indicated that 1-parent families (Odds Ratio = 0.62, 95% CIs = 0.50-0.76)
      lower parental education, (OR = 0.67, CI = 0.48-0.95 and OR = 0.77, CI = 0.61
      0.97), and youth age (OR = 0.70, CI = 0.55-0.88 and OR = 0.59, CI = 0.45-0.77)
      were the only demographic factors that independently, prospectively, and
      significantly predicted which youth would possess less than the median number of
      assets. CONCLUSIONS: Youth assets may be 1 mechanism that explains the negative
      effects of some demographic factors, particularly 1-parent families and low
      parent education, on youth risk behaviors and health.

PMID- 28760188
TI  - Perceived Barriers and Facilitators to Healthy Eating and School Lunch Meals
      among Adolescents: A Qualitative Study.
AB  - OBJECTIVES: We explored how perceived barriers and facilitators influence healthy
      eating and investigated the acceptability of changes to school lunch meals among
      adolescents after implementation of the Healthy, Hunger-Free Kids Act of 2010.
      METHODS: We conducted 8 focus groups with adolescents (N = 64) at 3 South Los
      Angeles high schools. Data collection instruments included a semi-structured
      guide and questionnaire. Two researchers independently coded transcripts.
      RESULTS: Most participants believed fruits and vegetables were available in their
      community and reported high relative cost, poor quality, and lack of motivation
      as barriers to consumption. Many said school meals were an important source of
      healthy food and were aware of recent changes to the school lunch program. A
      primary facilitator to eating school lunches was access to fresh food items (eg,
      a salad bar). Perceived barriers included long cafeteria lines, time constraints,
      lack of variety, and limited quantities of preferred items. Adolescents viewed
      off-campus food establishments near the school as competition to school meals.
      CONCLUSIONS: Our findings suggest the need to measure perceived and actual
      barriers to healthy eating among adolescents and to examine the effect of these
      barriers on dietary behavior. We provide programmatic and policy recommendations.

PMID- 28760189
TI  - Sleep Quality in Adolescents With Chronic Fatigue Syndrome/Myalgic
      Encephalomyelitis (CFS/ME).
AB  - STUDY OBJECTIVES: Little is known about the type and severity of sleep
      disturbances in the pediatric chronic fatigue syndrome/myalgic encephalomyelitis
      (CFS/ME) population, compared with healthy adolescents. Using a range of
      objective and subjective measures, the aim of this study was to investigate sleep
      quality, the relationship between objective and subjective measures of sleep
      quality, and their associations with anxiety in adolescents with CFS/ME compared
      with healthy controls. METHODS: Twenty-one adolescents with CFS/ME aged 13 to 18
      years (mean age 15.57 +/- 1.40), and 145 healthy adolescents aged 13 to 18 years
      (mean age 16.2 +/- 1.00) wore actigraphy watches continuously for 2 weeks to
      collect a number of objective sleep variables. The Pittsburgh Sleep Quality Index
      was used to obtain a subjective measure of sleep quality. Anxiety was measured by
      the Spence Children's Anxiety scale. RESULTS: On average over the 2-week period,
      adolescents with CFS/ME were found to have (1) significantly longer objective
      sleep onset latency, time in bed, total sleep time, and a later rise time (all P
      < .005), and (2) significantly poorer subjective sleep quality (P < .001),
      compared with healthy adolescents. The CFS/ME patient group displayed higher
      levels of anxiety (P < .05), and in both groups, higher levels of anxiety were
      significantly related to poorer subjective sleep quality (P < .001). CONCLUSIONS:
      This study provides objective and subjective evidence of sleep disturbance in
      adolescents with CFS/ME compared with healthy adolescent controls.

PMID- 28760190
TI  - Independent Contributions of Obstructive Sleep Apnea and the Metabolic Syndrome
      to the Risk of Chronic Kidney Disease.
AB  - STUDY OBJECTIVES: This retrospective study was conducted to evaluate the
      associations and interactions among obstructive sleep apnea (OSA), chronic kidney
      disease (CKD), and metabolic syndrome (MS). METHODS: This study included 1,732
      subjects (1,482 male and 250 female) in whom OSA was diagnosed by
      polysomnography. The severity of OSA was defined as mild, moderate, or severe
      with an apnea-hypopnea index (AHI) score of 5 to < 15, 15 to < 30, and >= 30
      events/h, respectively. CKD was defined as an estimated glomerular filtration
      rate < 60 mL/min/1.73 m2 or albuminuria. RESULTS: The prevalence of MS was 29.2%
      (n = 505). One hundred twenty-nine subjects (7.4%) had CKD. In subjects with MS,
      CKD prevalence increased progressively with OSA severity: 7.4%, 12.5%, and 15.8%
      in those with mild, moderate, or severe OSA, respectively (P = .025). Each 10
      point increment in AHI score was independently associated with a 1.15-fold higher
      prevalence of CKD [95% confidence interval (CI), 1.036-1.280; P = .009] after
      adjustment for all individual components of MS. On the contrary, in those without
      MS, AHI was not associated with increased odds for CKD [odds ratio, 1.054; 95%
      CI, 0.930-1.195]. CONCLUSIONS: The independent association between OSA severity
      and CKD prevalence was observed only in subjects with MS. Further studies are
      needed to ascertain if OSA contributes to the development of CKD in subjects with
      MS.

PMID- 28760191
TI  - Does Sleep Endoscopy Staging Pattern Correlate With Outcome of Advanced
      Palatopharyngoplasty for Moderate to Severe Obstructive Sleep Apnea?
AB  - STUDY OBJECTIVES: Although drug-induced sleep endoscopy (DISE) is an accepted
      method to localize upper airway obstruction, it is not known whether all sites
      identified by DISE must be treated to achieve sufficient apnea-hypopnea index
      (AHI) improvement. The aim of this study was to compare outcomes for unilevel
      (upper) versus multilevel DISE collapse patterns in a patient cohort that only
      underwent modern palatopharyngoplasty. Our hypothesis was that not all tongue
      base-level obstructions on DISE must be treated. METHODS: Thirty-eight patients
      with mean AHI of 45 events/h underwent DISE followed by palatopharyngoplasty.
      Outcome was measured by polysomnography or home sleep apnea testing. RESULTS:
      Eleven patients (29%) had multilevel, complete tongue base obstruction and
      nineteen (50%) had no obstruction. These two groups were similar in age, body
      mass index, and AHI; the complete group had smaller tonsils and higher tongue
      position. The postoperative success rate and AHI in the group without tongue base
      obstruction were not significantly different from those of the complete group
      (68%; 17.4 +/- 11.0 versus 73%; 15.4 +/- 20.5, P > .99). Seventeen patients (45%)
      had circumferential collapse of velum. The postoperative AHI was higher for
      patients with circumferential collapse (23.6 +/- 15.8 from 55.3 +/- 22.1 versus
      10.5 +/- 9.94 from 36.4 +/- 16.7, P < .0001), but both groups had clinically and
      statistically significant AHI reductions. CONCLUSIONS: Patients with multilevel
      obstruction on DISE, treated with palatopharyngoplasty alone, had similar AHI
      outcome as those with unilevel obstruction. Multilevel surgery may not be needed
      in some patients with a multilevel obstruction pattern. Circumferential collapse
      of velum, however, was associated with a higher residual AHI.

PMID- 28760192
TI  - Long Sleep Duration is Associated With Sarcopenia in Korean Adults Based on Data
      from the 2008-2011 KNHANES.
AB  - STUDY OBJECTIVES: Sarcopenia, or loss of muscle mass, occurs with aging and
      results in frailty, disability, cardiovascular disease, and insulin resistance.
      Recently, researchers have asserted that sarcopenia is not an inevitable process,
      but is a modifiable condition. Adequate sleep duration is also important to
      maintain good physical and mental health. Therefore, the aim of our study was to
      examine the association between sleep duration and sarcopenia in Korean adults.
      METHODS: Data from 16,148 participants (7,158 men and 8,990 women) were analyzed
      from the 2008-2011 Korean National Health and Nutrition Examination Survey
      (KNHANES). We defined sarcopenia as one standard deviation below the sex-specific
      means of the appendicular skeletal muscle/height-squared values of a young
      reference group. Participants were categorized into 5 groups according to sleep
      duration. The odds ratios (OR) and 95% confidence intervals (95% CI) for
      sarcopenia according to sleep duration were calculated using multiple logistic
      regression analysis. RESULTS: The prevalence of sarcopenia was 14.3% in the total
      population (males 18.7%, females 9.7%). Compared to the 7 hours of sleep group,
      the OR (95% CI) for sarcopenia of the long sleep duration group (9 hours or more)
      was 1.589 (1.100-2.295) after controlling for confounding factors. From the
      results of subgroup analysis, high-risk groups for sarcopenia are as follows: 40
      64 years old (OR = 1.868), normal body mass index (OR = 1.516), smoking (OR =
      2.219), no regular exercise (OR = 1.506) in long sleepers. CONCLUSIONS: Long
      sleep duration (9 hours or longer) is independently associated with sarcopenia in
      Korean adults.

PMID- 28760193
TI  - Sleep Characteristics and Temperament in Preterm Children at Two Years of Age.
AB  - STUDY OBJECTIVES: We aimed to compare 2-year-old children born preterm with
      children born full term regarding: (1) sleep characteristics, (2) temperament,
      and (3) relations between sleep pattern and habits and temperament. METHODS: The
      study included 51 preterm children with normal cognitive, language, and motor
      development (mean = 20.94 months, standard deviation [SD] = 4.08) and 57 full
      term children (mean = 21.19, SD = 4.32). To assess sleep-related difficulties and
      habits and child temperament, mothers completed the following questionnaires: the
      (1) Sleep Disturbance Scale for Children-adapted (SDSC); (2) Brief Infant Sleep
      Questionnaire (BISQ); and (3) Italian Temperament Questionnaires-version 12-36
      months (QUIT). RESULTS: Preterm children needed less support to fall asleep and
      fell asleep more often alone in their own bed compared to those born at full
      term; however, preterm children showed more frequent sleep difficulties, such as
      restlessness and breathing problems during the night. In addition, preterm
      children had lower scores in the temperamental dimension of attention and higher
      scores in negative emotionality than full-term children. Finally, sleep problems
      were correlated with higher motor activity, lower social orientation and
      attention, and increased negative emotionality; a shorter nocturnal sleep
      duration was related to higher motor activity and lower inhibition to novelty
      whereas an earlier rise time was associated with lower attention and social
      orientation. CONCLUSIONS: Preterm children showed sleep pattern problems and
      disturbance, predominance of attention problems, and negative emotionality
      related to sleep disruption.

PMID- 28760194
TI  - A Comparison of Uvulopalatopharyngoplasty and Modified Radiofrequency Tissue
      Ablation in Mild to Moderate Obstructive Sleep Apnea: A Randomized Clinical
      Trial.
AB  - STUDY OBJECTIVES: To compare the efficacy of modified radiofrequency tissue
      ablation (MRFTA) with uvulopalatopharyngoplasty (UPPP) based on both subjective
      and objective outcome measures in patients with mild to moderate obstructive
      sleep apnea (OSA). METHODS: Forty patients with mild to moderate OSA were
      randomly divided into UPPP and MRFTA groups. Evaluation was made based on the
      apneahypopnea index (AHI), Sleep Apnea Quality of Life Index (SAQLI) and Epworth
      Sleepiness Scale (ESS), immediately before the surgery and 6 months
      postoperatively. RESULTS: The postoperative AHI scores were improved
      significantly in both groups, although the postoperative AHI in the UPPP group
      was significantly lower than in the MRFTA group (P = .02). The difference between
      success rates for moderate OSA in UPPP and MRFTA was significant (77% versus 30%,
      P = .03) but there was no significant difference between success rates for mild
      OSA in UPPP and MRFTA groups (70% versus 50%, P = .36). Comparing postoperative
      ESS scores in the 2 groups showed no significant difference (P = .24). The
      postoperative scores in social interaction, treatment-related symptoms domain,
      and SAQLI total score were significantly higher in the MRFTA group. CONCLUSIONS:
      MRFTA as well as UPPP can greatly improve daytime sleepiness and AHI, especially
      in patients with mild OSA. MRFTA proved to be more effective than UPPP to enhance
      quality of life of patients with OSA. Further studies with longer follow-up are
      required to evaluate long-term safety and efficacy of these procedures.
      COMMENTARY: A commentary on this article appears in this issue on page 1023.
      CLINICAL TRIAL REGISTRATION: Trial name: Comparison of RFTA (Radio-Frequency
      Tissue-Ablation) and UPPP (Uvulopalatopharyngoplasty) in patients with mild to
      moderate obstructive sleep apnea. URL: http://en.search.irct.ir/view/18617.
      Registration number: IRCT2014060910160N3.

PMID- 28760195
TI  - Alcohol as a Trigger Affecting Symptom Severity and Frequency of Slow Wave Sleep
      Disorders.

PMID- 28760196
TI  - Effects of PEP-1-FK506BP on cyst formation in polycystic kidney disease.
AB  - Polycystic kidney disease (PKD) is one of the most common inherited disorders,
      involving progressive cyst formation in the kidney that leads to renal failure.
      FK506 binding protein 12 (FK506BP) is an immunophilin protein that performs
      multiple functions, including regulation of cell signaling pathways and survival.
      In this study, we determined the roles of PEP-1-FK506BP on cell proliferation and
      cyst formation in PKD cells. Purified PEP-1-FK506BP transduced into PKD cells
      markedly inhibited cell proliferation. Also, PEP-1-FK506BP drastically inhibited
      the expression levels of p-Akt, p-p70S6K, p-mTOR, and p-ERK in PKD cells. In a 3D
      culture system, PEP-1-FK506BP significantly reduced cyst formation. Furthermore,
      the combined effects of rapamycin and PEP-1-FK506BP on cyst formation were
      markedly higher than the effects of individual treatments. These results suggest
      that PEP-1-FK506BP delayed cyst formation and could be a new therapeutic strategy
      for renal cyst formation in PKD. [BMB Reports 2017; 50(9): 460-465].

PMID- 28760198
TI  - Silencing repetitive DNA.
AB  - Some RNAs in mammalian cells can help to silence the DNA they are transcribed
      from.

PMID- 28760197
TI  - Transforming growth factor beta1 enhances adhesion of endometrial cells to
      mesothelium by regulating integrin expression.
AB  - Endometriosis is the abnormal growth of endometrial cells outside the uterus,
      causing pelvic pain and infertility. Furthermore, adhesion of endometrial tissue
      fragments to pelvic mesothelium is required for the initial step of endometriosis
      formation outside uterus. TGF-beta1 and adhesion molecules importantly function
      for adhesion of endometrial tissue fragments to mesothelium outside uterus.
      However, the function of TGF-beta1 on the regulation of adhesion molecule
      expression for adhesion of endometrial tissue fragments to mesothelium has not
      been fully elucidated. Interestingly, transforming growth factor beta1 (TGF
      beta1) expression was higher in endometriotic epithelial cells than in normal
      endometrial cells. The adhesion efficiency of endometriotic epithelial cells to
      mesothelial cells was also higher than that of normal endometrial cells.
      Moreover, TGF-beta1 directly induced the adhesion of endometrial cells to
      mesothelial cells through the regulation of integrin of alphaV, alpha6, beta1,
      and beta4 via the activation of the TGF-beta1/TGF-betaRI/Smad2 signaling pathway.
      Conversely, the adhesion of TGF-beta1-stimulated endometrial cells to mesothelial
      cells was clearly reduced following treatment with neutralizing antibodies
      against specific TGF-beta1-mediated integrins alphaV, beta1, and beta4 on the
      endometrial cell membrane. Taken together, these results suggest that TGF-beta1
      may act to promote the initiation of endometriosis by enhancing integrin-mediated
      cell-cell adhesion. [BMB Reports 2017; 50(8): 429-434].

PMID- 28760199
TI  - Major satellite repeat RNA stabilize heterochromatin retention of Suv39h enzymes
      by RNA-nucleosome association and RNA:DNA hybrid formation.
AB  - The Suv39h1 and Suv39h2 histone lysine methyltransferases are hallmark enzymes at
      mammalian heterochromatin. We show here that the mouse Suv39h2 enzyme differs
      from Suv39h1 by containing an N-terminal basic domain that facilitates retention
      at mitotic chromatin and provides an additional affinity for major satellite
      repeat RNA. To analyze an RNA-dependent interaction with chromatin, we purified
      native nucleosomes from mouse ES cells and detect that Suv39h1 and Suv39h2
      exclusively associate with poly-nucleosomes. This association was attenuated upon
      RNaseH incubation and entirely lost upon RNaseA digestion of native chromatin.
      Major satellite repeat transcripts remain chromatin-associated and have a
      secondary structure that favors RNA:DNA hybrid formation. Together, these data
      reveal an RNA-mediated mechanism for the stable chromatin interaction of the
      Suv39h KMT and suggest a function for major satellite non-coding RNA in the
      organization of an RNA-nucleosome scaffold as the underlying structure of mouse
      heterochromatin.

PMID- 28760200
TI  - RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin.
AB  - Heterochromatin formed by the SUV39 histone methyltransferases represses
      transcription from repetitive DNA sequences and ensures genomic stability. How
      SUV39 enzymes localize to their target genomic loci remains unclear. Here, we
      demonstrate that chromatin-associated RNA contributes to the stable association
      of SUV39H1 with constitutive heterochromatin in human cells. We find that RNA
      associated with mitotic chromosomes is concentrated at pericentric
      heterochromatin, and is encoded, in part, by repetitive alpha-satellite
      sequences, which are retained in cis at their transcription sites. Purified
      SUV39H1 directly binds nucleic acids through its chromodomain; and in cells,
      SUV39H1 associates with alpha-satellite RNA transcripts. Furthermore, nucleic
      acid binding mutants destabilize the association of SUV39H1 with chromatin in
      mitotic and interphase cells - effects that can be recapitulated by RNase
      treatment or RNA polymerase inhibition - and cause defects in heterochromatin
      function. Collectively, our findings uncover a previously unrealized function for
      chromatin-associated RNA in regulating constitutive heterochromatin in human
      cells.

PMID- 28760201
TI  - Impact of nucleic acid and methylated H3K9 binding activities of Suv39h1 on its
      heterochromatin assembly.
AB  - SUV39H is the major histone H3 lysine 9 (H3K9)-specific methyltransferase that
      targets pericentric regions and is crucial for assembling silent heterochromatin.
      SUV39H recognizes trimethylated H3K9 (H3K9me3) via its chromodomain (CD), and
      enriched H3K9me3 allows SUV39H to target specific chromosomal regions. However,
      the detailed targeting mechanisms, especially for naive chromatin without
      preexisting H3K9me3, are poorly understood. Here we show that Suv39h1's CD
      (Suv39h1-CD) binds nucleic acids, and this binding is important for its function
      in heterochromatin assembly. Suv39h1-CD had higher binding affinity for RNA than
      DNA, and its ability to bind nucleic acids was independent of its H3K9me3
      recognition. Suv39h1 bound major satellite RNAs in vivo, and knockdown of major
      satellite RNAs lowered Suv39h1 retention on pericentromere. Suv39h1 mutational
      studies indicated that both the nucleic acid-binding and H3K9me-binding
      activities of Suv39h1-CD were crucial for its pericentric heterochromatin
      assembly. These results suggest that chromatin-bound RNAs contribute to creating
      SUV39H's target specificity.

PMID- 28760202
TI  - High-sensitivity C-reactive protein is an independent marker of abnormal coronary
      vasoreactivity in patients with non-obstructive coronary artery disease.
AB  - BACKGROUND: Coronary endothelial dysfunction (CED) is an early stage of
      atherosclerosis and is associated with adverse cardiovascular events.
      Inflammation may play a role in the development of endothelial dysfunction. To
      date no study has evaluated the relationship between C-reactive protein and CED.
      We aimed to determine if C-reactive protein is associated with CED. METHODS: In
      1016 patients (mean age 50.7+/-12.3 years, 34% male) presenting to the
      catheterization laboratory with chest pain and non-obstructive coronary artery
      disease, coronary vasoreactivity was assessed by measuring the percent change in
      coronary blood flow (%DeltaCBF) and coronary artery diameter (%DeltaCAD) in
      response to intracoronary acetylcholine. Plasma high sensitivity C-reactive
      protein (hs-CRP) was measured and patients were divided into 2 groups: hs
      CRP<=3.0 mg/L (low-intermediate cardiovascular risk n=169) and 3 mg/L<hs-CRP<=10
      mg/L (high cardiovascular risk n=847). RESULTS: Patients with a high risk hs-CRP
      had a significantly lower %DeltaCBF and %DeltaCAD in response to acetylcholine vs
      low risk hs-CRP (43.8+/-6.1 vs 65.8+/-4.5, P=.004 and -17.2+/-1.5 vs -13.1+/-0.8,
      P=.02 respectively). Low risk hs-CRP was associated with significantly higher
      %DeltaCBF and %DeltaCAD vs high risk hs-CRP (27.1+/-11.0, P=.01 and 4.5+/-1.9,
      P=.02 respectively). CED was associated with significantly higher hs-CRP levels
      and high risk hs-CRP was independently associated with abnormal coronary
      vasoreactivity, OR 1.82 (95% CI 1.25-2.69). CONCLUSIONS: Hs-CRP is independently
      associated with and a strong predictor of abnormal coronary vasoreactivity in
      patients with non-obstructive coronary artery disease.

PMID- 28760203
TI  - County socioeconomic characteristics and heart transplant outcomes in the United
      States.
AB  - BACKGROUND: Geographic disparities in survival after heart transplantation have
      received mixed support in prior studies, and specific geographic characteristics
      that might be responsible for these differences are unclear. We tested for
      differences in heart transplant outcomes across United States (US) counties after
      adjustment for individual-level covariates. Our secondary aim was to evaluate
      whether specific county-level socioeconomic characteristics explained geographic
      disparities in survival. METHODS: Data on patients aged >=18 years undergoing a
      first-time heart transplant between July 2006 and December 2014 were obtained
      from the United Network for Organ Sharing. Residents of counties represented by
      <5 patients were excluded. Patient survival (censored in March 2016) was analyzed
      using multivariable Cox regression. Shared frailty models were used to test for
      residual differences in overall all-cause mortality across counties after
      adjusting for recipient and donor characteristics. Measures of county economic
      disadvantage, inequality, and racial segregation were obtained from US Census
      data and coded into quintiles. A likelihood ratio test determined whether
      adjusting for each county measure improved the fit of the Cox model. RESULTS:
      Multivariable analysis of 10,879 heart transplant recipients found that,
      adjusting for individual-level characteristics, there remained statistically
      significant variation in mortality hazard across US counties (P=.004). Adjusting
      for quintiles of community disadvantage, economic inequality, or racial
      segregation did not significantly improve model fit (likelihood ratio test
      P=.092, P=.273, and P=.107, respectively) and did not explain residual
      differences in patient survival across counties. CONCLUSIONS: Heart
      transplantation outcomes vary by county, but this difference is not attributable
      to county-level socioeconomic disadvantage.

PMID- 28760204
TI  - Effects of serelaxin on the outcome of patients with or without substantial
      peripheral edema: A subgroup analysis from the RELAX-AHF trial.
AB  - BACKGROUND: Acute heart failure (AHF) is a heterogeneous disorder, with most of
      the patients presenting with breathlessness along with varying degrees of
      peripheral edema. The presence of peripheral edema suggests that volume overload
      is the cause of decompensation leading to AHF, whereas breathlessness in the
      absence of edema may reflect a "vascular phenotype." This analysis investigated
      the characteristics, therapeutic response, and outcome of patients with AHF, with
      and without overt peripheral edema in the RELAX-AHF trial. METHODS: Physician
      assessed edema scores at baseline were used to categorize the population into
      those with no/mild edema (score 0 or 1+) and moderate/severe edema (score 2+ or
      3+). The effect of serelaxin vs placebo was assessed within each subgroup.
      RESULTS: Patients with moderate/severe edema (n = 583; 50.5%) were more likely to
      have severe dyspnea, orthopnea (>30 degrees ), rales (>=1/3), and elevated
      jugular venous pressure (>6 cm) than the patients with little or no peripheral
      edema (n=571; 49.5%). The relative benefits of serelaxin in terms of reduction in
      breathlessness, lower diuretic requirements, decreased length of initial hospital
      stay and days in intensive care unit/cardiac care unit, and improved prognosis
      (180-day cardiovascular and all-cause mortality) were generally similar for
      patients with or without peripheral edema. However, because patients with
      moderate/severe peripheral edema had worse outcomes, the absolute benefit was
      generally greater than in patients with no/mild edema. CONCLUSIONS: Overall,
      patients with AHF and moderate/severe peripheral edema have a worse prognosis but
      appear to receive similar relative benefit and perhaps greater absolute benefit
      from serelaxin administration.

PMID- 28760207
TI  - The troponin decision-point dilemma: The 99th percentile solution "do the best
      you can [with cardiac troponin] until you know better. Then when you know better,
      do better." Maya Angelou, poet, dancer, producer, playwright, director, author.

PMID- 28760206
TI  - Prevention of sudden cardiac death in the young: Developing a rational, reliable,
      and sustainable national health care resource. A report from the Cardiac Safety
      Research Consortium.
AB  - This White Paper, prepared by members of the Cardiac Safety Research Consortium,
      discusses important issues regarding sudden cardiac death in the young (SCDY), a
      problem that does not discriminate by gender, race, ethnicity, education,
      socioeconomic level, or athletic status. The occurrence of SCDY has devastating
      impact on families and communities. Sudden cardiac death in the young is a matter
      of national and international public health, and its prevention has generated
      deep interest from multiple stakeholders, including families who have lost
      children, advocacy groups, academicians, regulators, and the medical industry. To
      promote scientific and clinical discussion of SCDY prevention and to germinate
      future initiatives to move this field forward, a Cardiac Safety Research
      Consortium-sponsored Think Tank was held on February 21, 2015 at the US Food and
      Drug Administration's White Oak facilities, Silver Spring, MD. The ultimate goal
      of the Think Tank was to spark initiatives that lead to the development of a
      rational, reliable, and sustainable national health care resource focused on SCDY
      prevention. This article provides a detailed summary of discussions at the Think
      Tank and descriptions of related multistakeholder initiatives now underway: it
      does not represent regulatory guidance.

PMID- 28760205
TI  - Probing oral anticoagulation in patients with atrial high rate episodes:
      Rationale and design of the Non-vitamin K antagonist Oral anticoagulants in
      patients with Atrial High rate episodes (NOAH-AFNET 6) trial.
AB  - : Oral anticoagulation prevents ischemic strokes in patients with atrial
      fibrillation (AF). Early detection of AF and subsequent initiation of oral
      anticoagulation help to prevent strokes in AF patients. Implanted cardiac
      pacemakers and defibrillators allow seamless detection of atrial high rate
      episodes (AHRE), but the best antithrombotic therapy in patients with AHRE is not
      known. RATIONALE: Stroke risk is higher in pacemaker patients with AHRE than in
      those without, but the available data also show that stroke risk in patients with
      AHRE is lower than in patients with AF. Furthermore, only a minority of patients
      with AHRE will develop AF, many strokes occur without a temporal relation to
      AHRE, and AHRE can reflect other arrhythmias than AF or artifacts. An adequately
      powered controlled trial of oral anticoagulation in patients with AHRE is needed.
      DESIGN: The Non-vitamin K antagonist Oral anticoagulants in patients with Atrial
      High rate episodes (NOAH-AFNET 6 ) trial tests whether oral anticoagulation with
      edoxaban is superior to prevent the primary efficacy outcome of stroke or
      cardiovascular death compared with aspirin or no antithrombotic therapy based on
      evidence-based indications. The primary safety outcome will be major bleeding.
      NOAH-AFNET 6 will randomize 3,400 patients with AHRE, but without documented AF,
      aged >=65 years with at least 1 other stroke risk factor, to oral anticoagulation
      therapy (edoxaban) or no anticoagulation. All patients will be followed until the
      end of this investigator-driven, prospective, parallel-group, randomized, event
      driven, double-blind, multicenter phase IIIb trial. Patients will be censored
      when they develop AF and offered open-label anticoagulation. The sponsor is the
      Atrial Fibrillation NETwork (AFNET). The trial is supported by the DZHK (German
      Centre for Cardiovascular Research), the BMBF (German Ministry of Education and
      Research), and Daiichi Sankyo Europe. CONCLUSION: NOAH-AFNET 6 will provide
      robust information on the effect of oral anticoagulation in patients with atrial
      high rate episodes detected by implanted devices.

PMID- 28760209
TI  - Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE-AF) randomized
      trial: Design and rationale.
AB  - BACKGROUND: Approximately 20% of ischemic strokes are associated with clinically
      apparent atrial fibrillation (AF). Regardless of stroke etiology, detection of AF
      in patients with ischemic strokes often changes antithrombotic treatment from
      anti-platelet to oral anticoagulation therapy. The role and the optimum duration
      of cardiac monitoring to detect AF in patients with strokes presumed due to large
      vessel atherosclerosis or small vessel disease is unknown. This manuscript
      describes the design and rationale of the STROKE-AF trial. STUDY DESIGN: STROKE
      AF is a randomized, controlled, open-label, post-market clinical trial. Detection
      of AF will be evaluated using continuous arrhythmia monitoring with an insertable
      cardiac monitor (ICM) compared with standard of care follow-up in patients with
      stroke (within the prior 10 days) that is presumed due to large vessel cervical
      or intracranial atherosclerosis, or to small vessel disease. Approximately 500
      patients will be enrolled at approximately 40 centers in the United States.
      Patients will be randomized 1:1 to arrhythmia monitoring with an ICM (continuous
      monitoring arm) or standard of care follow-up (control arm). Subjects will be
      followed for >=12 months and up to 3 years. OUTCOMES: The primary objective is to
      compare the incidence rate of detected AF through 12 months of follow-up between
      the two arms. CONCLUSION: This trial will provide information on the value of
      ICMs to detect subclinical AF in patients with stroke presumed due to large
      vessel atherosclerosis or small vessel disease, which will have implications for
      guiding treatment with oral anticoagulation for secondary stroke prevention.

PMID- 28760208
TI  - Use of troponin assay 99th percentile as the decision level for myocardial
      infarction diagnosis.
AB  - BACKGROUND: The Universal Definition of Myocardial Infarction recommends the 99th
      percentile concentration of cardiac troponin in a normal reference population as
      part of the decision threshold to diagnose type 1 spontaneous myocardial
      infarction. Adoption of this recommendation in contemporary worldwide practice is
      not well known. METHODS: We performed a cohort study of 276 hospital laboratories
      in 31 countries participating in the National Heart, Lung, and Blood Institute
      sponsored International Study of Comparative Health Effectiveness with Medical
      and Invasive Approaches trial. Each hospital laboratory's troponin assay
      manufacturer and model, the recommended assay's 99th percentile upper reference
      limit (URL) from the manufacturer's package insert, and the troponin
      concentration used locally as the decision level to diagnose myocardial
      infarction were ascertained. RESULTS: Twenty-one unique troponin assays from 9
      manufacturers were used by the surveyed hospital laboratories. The ratio of the
      troponin concentration used locally to diagnose myocardial infarction to the
      assay manufacturer-determined 99th percentile URL was <1 at 19 (6.6%)
      laboratories, equal to 1 at 91 (31.6%) laboratories, >1 to <=5 at 101 (35.1%)
      laboratories, >5 to <=10 at 34 (11.8%) laboratories, and >10 at 43 (14.9%)
      laboratories. The variability in troponin decision level for myocardial
      infarction relative to the assay 99th percentile URL was present for laboratories
      in and outside of the United States, as well as for high- and standard
      sensitivity assays. CONCLUSIONS: There is substantial hospital-level variation in
      the troponin threshold used to diagnose myocardial infarction; only one-third of
      hospital laboratories currently follow the Universal Definition of Myocardial
      Infarction consensus recommendation for use of troponin concentration at the 99th
      percentile of a normal reference population as the decision level to diagnose
      myocardial infarction. This variability across laboratories has important
      implications for both the diagnosis of myocardial infarction in clinical practice
      as well as adjudication of myocardial infarction in clinical trials.

PMID- 28760210
TI  - A randomized trial of a 1-hour troponin T protocol in suspected acute coronary
      syndromes: Design of the Rapid Assessment of Possible ACS In the emergency
      Department with high sensitivity Troponin T (RAPID-TnT) study.
AB  - BACKGROUND: Protocols incorporating high-sensitivity troponin to guide decision
      making in the disposition of patients with suspected acute coronary syndromes
      (ACS) in the emergency department have received a lot of attention.
      Traditionally, patients with chest pain have required long periods of observation
      in emergency department before being deemed safe for discharge. In an era of
      limited health service resources, a protocol that could discharge patients safely
      within an hour of presentation is extremely attractive. Unfortunately, despite
      incorporation into some guidelines, these protocols have not been subjected to
      randomized comparisons evaluating safety, effectiveness, and cost-effectiveness.
      OBJECTIVE: This study is designed to provide the evidence required to allow key
      decision makers to implement these protocols: specifically, to provide evidence
      that a decision rule based on 0- and 1-hour high-sensitivity troponin T (hs-TnT)
      is safe, provides noninferior outcomes in all patients with suspected ACS, and
      that implementation of a rapid troponin protocol leads to efficient care. DESIGN:
      This prospective pragmatic trial (n=5,400, 5 hospitals) randomly allocates
      patients with suspected ACS to either a 0/1-hour hs-TnT protocol as advocated in
      clinical guidelines, versus usual care of standard troponin reporting evaluated
      at 3 and 6hours. The primary effectiveness composite end points of this study are
      all-cause death and new/recurrent ACS within 30days. To evaluate cost
      effectiveness, follow-up will determine clinical events, quality of life, and
      resource utilization within 12 months. SUMMARY: Demonstrating that a 0/1-hour hs
      TnT protocol improves the effectiveness and efficiency of care within a robust
      comparative study will fill an evidence gap that currently limits the translation
      of more precise hs-TnT testing into better patient and health service outcomes.

PMID- 28760211
TI  - Implantable cardiac monitors in high-risk post-infarction patients with cardiac
      autonomic dysfunction and moderately reduced left ventricular ejection fraction:
      Design and rationale of the SMART-MI trial.
AB  - BACKGROUND: Most deaths after myocardial infarction (MI) occur in patients with
      left ventricular ejection fraction (LVEF) >35%, for whom no specific prophylactic
      strategies exist. Deceleration capacity (DC) of heart rate and periodic
      repolarization dynamics (PRD) are noninvasive electrophysiological markers
      depending on the vagal and sympathetic tone. The combination of abnormal DC
      and/or PRD identifies a new high-risk group among postinfarction patients with
      LVEF 36%-50%. This new high-risk group has similar characteristics with respect
      to prognosis and patient numbers to those of the established high-risk group
      identified by LVEF <= 35%. STUDY DESIGN: The SMART-MI trial is an investigator
      initiated randomized prospective multicenter trial that tests the efficacy of
      implantable cardiac monitors (ICM) in this new high-risk group. The study will
      enroll approximately 1,600 survivors of acute MI with sinus rhythm and an LVEF of
      35%-50% in 17 centers in Germany who will be tested for presence of cardiac
      autonomic dysfunction. Four hundred patients with either abnormal DC (<=2.5 ms)
      and/or PRD (>=5.75deg2) will be randomized in a 1:1 fashion to intensive follow
      up via telemonitoring using an ICM device (experimental arm) or conventional
      follow-up (control arm). For the ICM arm, specific treatment paths have been
      developed according to current guidelines. OUTCOMES: The primary end point is
      time to detection of predefined serious arrhythmic events during follow-up,
      including atrial fibrillation >=6minutes, nonsustained ventricular tachycardia
      (cycle length<=320 ms; >=40 beats), atrioventricular block >=IIb, and sustained
      ventricular tachycardia/ventricular fibrillation. The median follow-up period is
      18months with a minimum follow-up of 6months. The effect of remote monitoring on
      clinical outcomes will be tested as secondary outcome measure (ClinicalTrials.gov
      NCT02594488).

PMID- 28760212
TI  - Brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism is associated
      with disease severity and incidence of cardiovascular events in a patient cohort.
AB  - BACKGROUND: The rs6265 (Val66Met) single-nucleotide polymorphism in the BDNF gene
      has been related to a number of endophenotypes that have in turn been shown to
      confer risk for atherosclerotic cardiovascular disease (CVD). To date, however,
      very few studies have examined the association of the Val66Met single-nucleotide
      polymorphism with CVD clinical outcomes. METHODS: In a cohort of 5,510 Caucasian
      patients enrolled in the CATHeterization GENetics (CATHGEN) study at Duke
      University Hospital between 2001 and 2011, we determined the severity of coronary
      artery disease (CAD) and CVD event incidence through up to 11.8years of follow
      up. We examined the association of Val66Met genotype with time-to-death or
      myocardial infarction, adjusting for age, sex, CAD risk variables, and CAD
      severity measures. RESULTS: The Val/Val genotype was associated with a higher
      risk than Met carriers for clinical CVD events (P=.034, hazard ratio 1.12, 95% CI
      1.01-1.24). In addition, compared with Met carriers, individuals with the Val/Val
      genotype had a greater odds of having more diseased vessels (odds ratio 1.17, 95%
      CI 1.06-1.30, P=.002), and lower left ventricular ejection fraction (beta=-0.72,
      95% CI, -1.42 to -0.02, P=.044). CONCLUSIONS: The Val/Val genotype was associated
      with greater severity of CAD and incidence of CVD-related clinical events in a
      patient sample. If these findings are confirmed in further research, intervention
      studies in clinical groups with the Val/Val genotype could be undertaken to
      prevent disease and improve prognosis.

PMID- 28760213
TI  - Retained cardiac implantable electronic device fragments are not associated with
      magnetic resonance imaging safety issues, morbidity, or mortality after
      orthotopic heart transplant.
AB  - BACKGROUND: Cardiac implantable electronic device therapy (CIED) has
      revolutionized treatment for advanced heart failure. Most patients considered for
      orthotopic heart transplantation (OHT) are treated with implantable cardioverter
      defibrillators, cardiac resynchronization therapy, or both. These CIEDs are
      surgically extracted at the time of transplant. Occasionally, CIEDs are
      incompletely removed. Little is known about the outcomes of post-OHT patients
      with retained CIED fragments. METHODS: We identified 200 consecutive patients
      that underwent OHT at our institution between April 2006 and December 2014 and
      performed a retrospective analysis of available radiographic images and clinical
      records. Chest radiographs prior to and following OHT were reviewed for the
      presence of CIED or retained CIED fragments. The outcomes of patients with
      retained CIED fragments that had subsequent magnetic resonance imaging (MRI)
      studies performed were further investigated. RESULTS: One hundred eighty of 200
      patients were identified as having CIED prior to OHT, of which 29 had retained
      CIED fragments after OHT. Most retained CIED fragments originated from superior
      vena cava defibrillator coils. There were no adverse events in the retained CIED
      fragment cohort, and survival was unaffected. Ten patients with retained CIED
      fragments safely underwent a total of 28 MRIs after OHT, all of diagnostic
      quality. CONCLUSION: Retained CIED fragments are not associated with adverse
      events or increased mortality after OHT. Diagnostic MRI has been safely performed
      in patients with retained CIED fragments after incomplete device extraction.
      Retrieval of these fragments prior to MRI does not appear warranted given the
      demonstrated safety and preserved image quality in this population.

PMID- 28760214
TI  - Clinical outcomes with percutaneous coronary revascularization vs coronary artery
      bypass grafting surgery in patients with unprotected left main coronary artery
      disease: A meta-analysis of 6 randomized trials and 4,686 patients.
AB  - : Some but not all randomized controlled trials (RCT) have suggested that
      percutaneous coronary intervention (PCI) with drug-eluting stents may be an
      acceptable alternative to coronary artery bypass grafting (CABG) surgery for the
      treatment of unprotected left main coronary artery disease (ULMCAD). We therefore
      aimed to compare the risk of all-cause mortality between PCI and CABG in patients
      with ULMCAD in a pairwise meta-analysis of RCT. METHODS: Randomized controlled
      trials comparing PCI vs CABG for the treatment of ULMCAD were searched through
      MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings.
      RESULTS: Six trials including 4,686 randomized patients were identified. After a
      median follow-up of 39 months, there were no significant differences between PCI
      vs CABG in the risk of all-cause mortality (hazard ratio [HR] 0.99, 95% CI 0.76
      1.30) or cardiac mortality. However, a significant interaction for cardiac
      mortality (Pinteraction= .03) was apparent between randomization arm and SYNTAX
      score, such that the relative risk for mortality tended to be lower with PCI
      compared with CABG among patients in the lower SYNTAX score tertile, similar in
      the intermediate tertile, and higher in the upper SYNTAX score tertile.
      Percutaneous coronary intervention compared with CABG was associated with a
      similar long-term composite risk of death, myocardial infarction, or stroke (HR
      1.06, 95% CI 0.82-1.37), with fewer events within 30 days after PCI offset by
      fewer events after 30 days with CABG (Pinteraction < .0001). Percutaneous
      coronary intervention was associated with greater rates of unplanned
      revascularization compared with CABG (HR 1.74, 95% CI 1.47-2.07). CONCLUSIONS: In
      patients undergoing revascularization for ULMCAD, PCI was associated with similar
      rates of mortality compared with CABG at a median follow-up of 39 months, but
      with an interaction effect suggesting relatively lower mortality with PCI in
      patients with low SYNTAX score and relatively lower mortality with CABG in
      patients with high SYNTAX score. Both procedures resulted in similar long-term
      composite rates of death, myocardial infarction, or stroke, with PCI offering an
      early safety advantage and CABG demonstrating greater durability.

PMID- 28760215
TI  - Interventions Supporting Long-term Adherence aNd Decreasing cardiovascular events
      (ISLAND): Pragmatic randomized trial protocol.
AB  - BACKGROUND: Guidelines recommend cardiac rehabilitation and long-term use of
      cardiac medications for most patients who have had a myocardial infarction (MI),
      but adherence to these secondary prevention treatments is suboptimal. METHODS:
      This is a multicenter, pragmatic, 3-arm randomized trial. Eligible patients (n =
      2,742) with obstructive coronary artery disease are randomized post-MI to usual
      care or 1 of 2 intervention arms. Patients in the first intervention arm receive
      mail-outs sent on behalf of their cardiologist at 4, 8, 20, 32, and 44 weeks post
      MI; content is designed to address determinants of adherence and facilitate
      discussion between the patient and their health care team. Patients in the second
      intervention arm receive mail-outs plus automated interactive voice response
      system telephone calls 2 weeks after each letter, as well as a telephone call by
      trained lay health workers if the interactive voice response system identifies
      challenges with adherence. Outcomes are assessed 12 months post-MI via patient
      self-report and administrative data sources. Co-primary outcomes are adherence to
      cardiac medications and completion of cardiac rehabilitation. Secondary outcomes
      include cardiovascular events and mortality. An embedded, theory-informed process
      evaluation will explore the mechanism of action; an economic evaluation is also
      planned. CONCLUSIONS: We describe a complete program evaluation of a highly
      pragmatic, health-system intervention to support adherence to recommended
      treatments. Research ethics boards approved waiver of consent for patients
      enrolled in the trial with provision of multiple opportunities to opt out and a
      debrief at the time of outcome assessment. The methods used here may provide a
      model for similar interventions.

PMID- 28760216
TI  - Use of endpoint adjudication to improve the quality and validity of endpoint
      assessment for medical device development and post marketing evaluation:
      Rationale and best practices. A report from the cardiac safety research
      consortium.
AB  - This white paper provides a summary of presentations, discussions and conclusions
      of a Thinktank entitled "The Role of Endpoint Adjudication in Medical Device
      Clinical Trials". The think tank was cosponsored by the Cardiac Safety Research
      Committee, MDEpiNet and the US Food and Drug Administration (FDA) and was
      convened at the FDA's White Oak headquarters on March 11, 2016. Attention was
      focused on tailoring best practices for evaluation of endpoints in medical device
      clinical trials, practical issues in endpoint adjudication of therapeutic,
      diagnostic, biomarker and drug-device combinations, and the role of adjudication
      in regulatory and reimbursement issues throughout the device lifecycle. Attendees
      included representatives from medical device companies, the FDA, Centers for
      Medicare and Medicaid Services (CMS), end point adjudication specialist groups,
      clinical research organizations, and active, academically based adjudicators. The
      manuscript presents recommendations from the think tank regarding (1) rationale
      for when adjudication is appropriate, (2) best practices establishment and
      operation of a medical device adjudication committee and (3) the role of endpoint
      adjudication for post market evaluation in the emerging era of real world
      evidence.

PMID- 28760217
TI  - Time in therapeutic range and major adverse outcomes in atrial fibrillation
      patients undergoing percutaneous coronary intervention: The Atrial Fibrillation
      Undergoing Coronary Artery Stenting (AFCAS) registry.
AB  - BACKGROUND: Combination of oral anticoagulation (OAC) and antiplatelets is used
      in atrial fibrillation (AF) patients undergoing percutaneous coronary
      intervention and stent (PCI-S) procedure but is associated with increased
      bleeding when triple antithrombotic therapy (TAT) is used. Our aim was to analyze
      the impact of time in therapeutic range (TTR) on outcomes, in patients prescribed
      with TAT. METHODS: Ancillary analysis from the AFCAS registry in patients
      assigned to TAT. TTR was calculated with Rosendaal method. Outcomes were analyzed
      according to TTR tertiles (T1 [<=56.8%] vs. T2 [56.9-93.8%] vs. T3 [>=93.9%]).
      Major bleeding was the primary outcome. RESULTS: Of 963 patients enrolled,
      470(48.8%) were prescribed with TAT at discharge and qualified for this analysis.
      Median [IQR] TTR was 80.0% [45.3-100%]. After 359 [341-370] days, major bleeding
      rates were progressively lower with increasing TTR tertiles (T1 vs. T2 vs. T3:
      10.3% vs. 4.7% vs. 2.3%, P=.006). Kaplan-Meier analysis demonstrated a
      progressively lower risk for major bleeding across tertiles (P=.006). Patients in
      the highest TTR tertile had a non-significant lower risk for major adverse
      coronary and cerebrovascular events (MACCE) (log-rank: 4.905, P=.086). Cox
      regression analysis showed that T2 and T3 were inversely associated with major
      bleeding (hazard ratio [HR]:0.39, P=.050 and HR: 0.21, P=.005). Continuous TTR
      was inversely associated with major bleeding (HR: 0.98, P<.001). For MACCE,
      adjusted Cox analysis found a non-significant lower risk for T3 (HR: 0.64,
      P=.128). CONCLUSIONS: In AF patients undergoing PCI-S prescribed TAT, good
      quality anticoagulation control (as reflected by TTR) was closely related to
      bleeding outcomes during follow-up. Despite some suggestive trends for an inverse
      relationship between TTR and MACCE, no definitive conclusions can be drawn, and
      further large studies are needed.

PMID- 28760218
TI  - Growth-differentiation factor 15 and risk of major bleeding in atrial
      fibrillation: Insights from the Randomized Evaluation of Long-Term
      Anticoagulation Therapy (RE-LY) trial.
AB  - OBJECTIVE: To evaluate and validate the prognostic value of growth
      differentiation factor 15 (GDF-15) beyond clinical characteristics and other
      biomarkers concerning bleeding and stroke outcomes in patients with atrial
      fibrillation in the RE-LY trial. METHODS: GDF-15 was measured in samples
      collected at randomization in 8,474 patients with a median follow-up time of 1.9
      years. Patients were stratified based on predefined GDF-15 cutoffs: group 1,
      <1,200 ng/L (the 90th percentile in healthy individuals); group 2, 1,200-1,800;
      and group 3, >1,800 ng/L (high-risk individuals). Efficacy and safety outcomes
      were compared across groups of GDF-15 in Cox models adjusted for baseline
      characteristics, cardiac (N-terminal pro-b-type natriuretic peptide, high
      sensitive troponin T), inflammatory (interleukin 6, C-reactive protein) and
      coagulation (D-dimer) biomarkers, and randomized treatment. RESULTS: GDF-15
      concentrations were <1,200 ng/L in 2,647 (31.2%), between 1,200 and 1,800 ng/L in
      2,704 (31.9%), and >1,800 ng/L in 3,123 (36.9%) participants, respectively.
      Annual rates of stroke, major bleeding, and mortality increased with higher GDF
      15 levels. The prognostic value of GDF-15 was independent of clinical
      characteristics for these outcomes. In models also adjusted for biomarkers, GDF
      15 remained significantly associated with major bleeding (hazard ratio [95% CI]
      group 3 vs group 1 1.76 [1.28-2.42], P < .0005) and all-cause mortality (hazard
      ratio 1.72 [1.30-2.29], P < .0005). GDF-15 improved the c index of both the HAS
      BLED (0.62-0.69) and ORBIT (0.68-0.71) bleeding risk scores. CONCLUSIONS: In
      patients with atrial fibrillation, GDF-15 is an independent risk indicator for
      major bleeding and all-cause mortality, but not for stroke. Therefore, GDF-15
      seems useful as a specific marker of bleeding in patients with AF on oral
      anticoagulant treatment.

PMID- 28760219
TI  - Epidemiology and clinical management of type 2 diabetes mellitus and associated
      comorbidities in Spain (e-Management study).
AB  - Type 2 diabetes mellitus is currently the most frequent chronic metabolic
      disease. In spain, according to the di@bet.es study, its prevalence is 13.8% in
      the adult population (although it is undiagnosed in 6%). The main risk factor for
      type 2 diabetes mellitus is obesity. The severity of type 2 diabetes mellitus is
      determined not only by the presence of hyperglycaemia, but also by the
      coexistence of other risk factors such as hypertension or dyslipidaemia, which
      are often associated with the disease. Its impact on the presence of chronic
      diabetic complications varies. While hyperglycaemia mainly influences the
      presence of microvascular complications, hypertension, dyslipidaemia and smoking
      play a greater role in macrovascular atherosclerotic disease. One of the most
      powerful ways to study the epidemiology of the disease is through the use of
      large databases that analyse the situation in the routine clinical management of
      huge numbers of patients. Recently, the data provided by the e-Management
      Project, based on the SIDIAP database, have allowed updating of many data on the
      health care of diabetic persons in Catalonia. This not only allows determination
      of the epidemiology of the disease but is also a magnificent starting point for
      the design of future studies that will provide answers to more questions.
      However, the use of large databases is not free of certain problems, especially
      those concerning the reliability of registries. This article analyses some of the
      data obtained by the e-Management study and other spanish epidemiological studies
      of equal importance.

PMID- 28760220
TI  - Weight and type 2 diabetes: new recommendations.
AB  - Most patients with type 2 diabetes have excess adiposity. There is wide consensus
      that adequate treatment of type 2 diabetes requires a simultaneous approach to
      overweight/obesity and the remaining cardiovascular risk factors. Non
      pharmacological interventions (diet, exercise) represent the cornerstone of the
      treatment of patients with type 2 diabetes. Weight loss through lifestyle
      modification has shown clear benefits in these patients, requiring an
      individualised and multidisciplinary approach with structured programmes endowed
      with specific resources. The weight gain associated with some antidiabetic drugs
      (secretagogues, glitazones, insulin) can hamper glycaemic control, compromising
      treatment adherence, worsening vascular risk profile, and limiting the benefits
      of treatment. Therefore, the current tendency is to adopt a weight-centred
      approach to the treatment of type 2 diabetes, giving priority to those
      antidiabetic drugs that have a neutral effect on weight or that favour weight
      loss (metformin, incretin therapies, sodium-glucose cotransporter-2 inhibitors).
      Metabolic surgery is an effective alternative for patients with type 2 diabetes
      and a BMI >=35 kg/m2 and allows remission of diabetes in a large proportion of
      patients, especially if the disease is not very advanced. A consensus document
      supported by various Spanish scientific societies has recently been published.
      This document makes a series of specific recommendations on the diagnostic and
      therapeutic approach to patients with diabetes and obesity.

PMID- 28760221
TI  - Approaching to DM2 through sodium-glucose cotransporter-2: does it make sense?
AB  - The kidney is involved in glucose homeostasis through three main mechanisms:
      renal gluconeogenesis, renal glucose consumption and glucose reabsorption in the
      proximal tubule. Glucose reabsorption is one of the most relevant physiological
      functions of the kidney, through which filtered glucose is fully recovered, urine
      is free of glucose, and calorie loss is prevented. Approximately 90% of the
      glucose is reabsorbed in the S1 segment of the proximal tubule, where GLUT2 and
      SGLT2 transporters are located, while the remaining 10% is reabsorbed in the S3
      segment by SGLT1 and GLUT1 transporters. In patients with hyperglycaemia, the
      kidney continues reabsorbing glucose, and hyperglycaemia is maintained. Most
      renal glucose reabsorption is mediated by the SGLT2 transporter. Several
      experimental and clinical studies suggest that pharmacological blockade of this
      transporter might be beneficial in the management of hyperglycemia in patients
      with type 2 diabetes.

PMID- 28760222
TI  - Clinical relevance of the selectivity of sodium-glucose cotransporter-2
      inhibitors.
AB  - Selectivity is the property of a drug to preferentially bind to a biological
      structure. Most drugs can bind and stimulate or inhibit more than one system.
      Therefore, it is important that they are selective for the intended site and that
      the doses used do not have effects on other sites, which could provoke adverse
      reactions. Selectivity is assessed through in vitro experiments on organs or
      isolated cells. If the aim is to compare drugs, the experiment should be
      conducted in the same tissue and with the same design. Even so, the results
      cannot be directly extrapolated to clinical practice due to the influence of
      pharmacokinetic properties, which allow an adequate dose of the drug to reach the
      target site. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are able to
      inhibit renal SGLT2 without modifying intestinal SGLT1, whose inhibition could
      produce gastrointestinal adverse reactions. The concentration needed to inhibit
      each of the transporters is calculated, as well as the ratio between the
      concentration that inhibits SGLT1 and the concentration needed to inhibit SGLT2.
      The higher the ratio, the greater the selectivity and the lower the risk of
      gastrointestinal adverse reactions. The three SGLT2i recently introduced in the
      therapeutic arsenal are sufficiently selective for SGLT2 to make effects on
      intestinal SGLT1 unlikely. To differentiate the components of this therapeutic
      class, its pharmacokinetic properties should be analysed rather than its
      pharmacodynamic characteristics, such as selectivity.

PMID- 28760223
TI  - Clinical profile of patients with type 2 diabetes mellitus treated with sodium-
      glucose cotransporter-2 inhibitors and experience in real-world clinical practice
      in Spain.
AB  - The main aim of the treatment of type 2 diabetes is overall control of
      cardiovascular risk factors. Almost 50% of patients with type 2 diabetes do not
      achieve glycaemic targets, and a much higher percentage do not achieve weight and
      blood pressure targets, despite the therapeutic arsenal that has appeared in the
      last decade for the treatment of this disease. In addition, antidiabetic
      secretatogues and insulin are associated with weight gain and an increased risk
      of hyperglycaemic episodes. Clinical practice guidelines recommend sodium-glucose
      cotransporter-2 inhibitors (SGLT2i) as an alternative in the same therapeutic
      step as the other options after initiation of metformin therapy. The present
      study reviews the most appropriate patient profile for SGLT2i therapy, based on
      their safety and efficacy demonstrated in controlled clinical trials. The article
      discusses which patients are at risk of experiencing the possible secondary
      effects due to the mechanism of action of this new therapeutic class, in whom
      SGLT2i should be used with caution. These considerations on the profile of
      patients suitable for SGLT2i therapy are contrasted with the results obtained in
      daily clinical practice, both in retrospective studies from other countries and
      from real-world experiences in Spain. This article presents a selection of
      studies performed in distinct centres with a minimum follow-up of 6 months and
      compares their results with those from clinical trials. SGLT2i are used in
      clinical practice in any therapeutic step and the efficacy results are very
      similar to those reported by controlled clinical trials, with a slightly higher
      proportion of genitourinary infections and a low dropout rate. Half the reported
      patients are diabetics receiving insulin therapy plus a gliflozin, showing the
      wide uptake of this therapeutic strategy by clinicians. SGLT2i are especially
      attractive due to their additional effectiveness in weight and blood pressure
      control and the possibility of using them in association with other antidiabetic
      agents or in monotherapy in patients at any stage of type 2 diabetes.

PMID- 28760224
TI  - Hemodynamic and renal implications of sodium-glucose cotransporter- 2 inhibitors
      in type 2 diabetes mellitus.
AB  - In DM2, there is increased expression of the proximal glucose transporter SGLT2.
      The increased glucose reabsorption from the urine to the proximal tubule and
      subsequently to the bloodstream, has three direct effects on the prognosis of
      patients with DM2: a) it increases the daily glucose load by raising the renal
      threshold for glucose, thus augmenting requirements for oral antidiabetics and
      insulin. This progressive increase occurs throughout the course of the disease
      and in parallel with the increase in renal mass (renal hypertrophy); b) because
      of the greater glucose reabsorption, glycosuria is lower than the level
      corresponding to glycaemia, decreasing the stimulus on the tubuloglomerular
      feedback system of the distal nephron. As a result, the glomerular vasodilation
      caused by hyperglycaemia is not arrested, maintaining glomerular hyperfiltration,
      and c) the excess glucose transported to the proximal tubular cells modifies
      their redox status, increasing local production of glycosylating products and
      activating local production of proinflammatory and profibrotic proliferative
      mediators. These mediators are responsible for the direct free radical damage to
      proximal tubular cells, for increased SGLT2 expression, increased production of
      collagen IV and extracellular matrix, and activation of monocyte/macrophages able
      to cause endothelial injury. The use of SGLT2 inhibitors not only reduces the
      reabsorption of glucose from the glomerular filtrate back into the
      circulationthus improving metabolic control in diabetesbut also restores
      tubuloglomerular feedback by increasing glycosuria and distal urinary flow.
      However, the most notable effect is due to inhibition of glucose entry to the
      proximal tubular cells. Glycosuria is toxic to the kidney: it harms
      glucosetransporting cells, that is, the proximal cells, which contain SGLT2. In
      animal models, SGLT2 inhibition reduces local production of oxygen-free radicals,
      the formation of mesangial matrix and collagen IV, glomerular infiltration by
      inflammatory cells and monocyte/macrophage-dependent arteriosclerosis. In humans,
      SGLT2 have a demonstrated ability to reduce renal injury and cardiovascular risk
      in patients with type 2 diabetes mellitus.

PMID- 28760225
TI  - Renal safety profile of sodium-glucose cotransporter-2 inhibitors and other
      safety data.
AB  - The main effect of SGLT2 inhibitors is their glycosuric action. These drugs
      reverse the deleterious effect of increased glucose reabsorption by the renal
      tubule in persons with DM2. In terms of efficacy, SGLT2 inhibitors produce a mean
      HbA1c reduction of 0.8%, although higher initial HbA1c levels can show a larger
      decrease. In addition to these glycaemic effects, this drug class also favours
      weight loss and blood pressure control, without increasing hypoglycaemic
      episodes. Due to their insulin-independent mechanism of action, SGLT2 inhibitors
      can be used in monotherapy, in patients with metformin intolerance, or in
      combination with other glucose-lowering drugs, including insulin. These drugs
      have few secondary effects and most are related to their mechanism of action. The
      most frequent adverse effects are genitourinary infections, usually mycotic
      infections. SGLT2 inhibitors have an adequate cardiovascular safety profile. The
      development of ketoacidosis remains to be elucidated, and may be related to use
      in patients with insulinopenia. A randomised clinical trial of an SGLT2 inhibitor
      in patients with DM2 and underlying cardiovascular disease showed that its use in
      association with standard therapy slowed the progression of renal damage and
      reduced significant renal events such as doubling of serum creatinine values and
      initiation of dialysis. These effects are probably due to the favourable effects
      of SGLT2 inhibition on glomerular haemodynamics, by reducing hyperfiltration, to
      the reduction of glucose-induced tubular toxicity, as well as its beneficial
      effects on glycaemia, blood pressure, weight, and uricaemia.

PMID- 28760226
TI  - Positioning of sodium-glucose cotransporter-2 inhibitors in national and
      international guidelines.
AB  - Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) selectively and reversibly
      inhibit sodium-glucose cotransporter-2 (SGLT2), promoting renal glucose excretion
      and reducing plasma glycaemia. By increasing renal glucose excretion, these drugs
      favour a negative energy balance, leading to weight loss. Their glucoselowering
      effect is independent of insulin. Although these drugs have only recently been
      developed, they have been included in all the main national and international
      guidelines since 2014. The present review summarises the most important
      recommendations on the use of SGLT2 in patients with DM2 contained in the most
      recently published guidelines and consensus statements.

PMID- 28760227
TI  - Relevance of weight in the management of patients with type 2 diabetes mellitus:
      towards an adipocentric approach to diabetes.
AB  - In recent decades, there has been a worldwide parallel increase in the prevalence
      of obesity and type 2 diabetes mellitus (T2DM), which is not surprising, given
      that increased visceral fat is the main risk factor for the development of T2DM
      in genetically predisposed individuals. An intervention focused on intensive
      blood glucose control in T2DM with classic drugs increases the risk of weight
      gain and the rate of hypoglycaemia. In contrast, weight loss through lifestyle
      changes, drugs and/or surgery simultaneously improves most cardiovascular (CV)
      risk factors, including hyperglycemia. Intensive intervention on lifestyle
      induces an overall benefit in patients with T2DM, but long-term weight loss is
      modest and has not been shown to reduce CV morbidity and mortality. The emergence
      of new therapeutic classes for T2DM and obesity, which simultaneously improve
      HbA1c, weight and other CV risk factors without inducing hypoglycaemia,
      represents a major change in the management of patients with diabesity. A sodium
      glucose cotransporter-2 inhibitor and a GLP-1 receptor agonist have recently been
      shown to decrease CV and total mortality in type 2 diabetic patients with CV
      disease. Furthermore, bariatric surgery rapidly induces remission or improvement
      of T2DM in a large percentage of patients and reduces diabetes-related mortality.
      The emergence of new therapies raises the possibility of changing the current
      glucose-centred therapeutic strategy for a weight-centred approach.

PMID- 28760228
TI  - Role of Mass Spectrometry in Clinical Endocrinology.
AB  - The advent of mass spectrometry into the clinical laboratory has led to an
      improvement in clinical management of several endocrine diseases. Liquid
      chromatography tandem mass spectrometry found some of its first clinical
      applications in the diagnosis of inborn errors of metabolism, in quantitative
      steroid analysis, and in drug analysis laboratories. Mass spectrometry assays
      offer analytical sensitivity and specificity that is superior to immunoassays for
      many analytes. This article highlights several areas of clinical endocrinology
      that have witnessed the use of liquid chromatography tandem mass spectrometry to
      improve clinical outcomes.

PMID- 28760229
TI  - Point-of-Care Endocrine Diagnostics.
AB  - Endocrinology relies on hormone and metabolite measurement for public health
      screening, diagnostics, and disease management. Advances in microfluidics,
      immunoassay technology, electronics, and software are moving in vitro endocrine
      diagnostics from the laboratory to the point of care. Point-of-care endocrine
      diagnostics provide results clinically equivalent to those produced by expensive
      laboratory instrumentation for a fraction of the cost and with a substantially
      more rapid turnaround time. Similar to the transformation of mainframe computers
      into laptops, tablets, and smartphones, clinical laboratories are evolving into
      point-of-care technologies.

PMID- 28760231
TI  - Biochemical Testing Relevant to Bone.
AB  - Laboratory biochemical testing is critical to the clinical understanding of bone
      disorders. Patients with skeletal diseases have underlying themes in their
      pathophysiology that would be impossible to detect without biochemical assessment
      of serum and urine minerals, vitamin D, parathyroid hormone, parathyroid hormone
      related peptide, and bone turnover markers. Bone disorders are caused by
      abnormalities in signaling pathways that affect bone formation and resorption.
      Therapies for common bone diseases were developed in direct response to
      underlying biochemical abnormalities.

PMID- 28760232
TI  - Biochemical Testing in Neuroendocrine Tumors.
AB  - Neuroendocrine cells are widely distributed throughout the body. They can
      produce, store, and secrete peptides and biogenic amines. Neuroendocrine tumors
      (NETs) are rare, but most are found in the intestine, pancreas, and lung. NETs
      may cause specific hormonal symptoms (eg, carcinoid syndrome) or appear
      nonfunctional. Blood or urine concentrations of tumor-secreted amines and
      peptides have been used as biomarkers in the diagnosis and management of NETs.
      This article focuses on currently available biochemical testing of blood or urine
      for gastroenteropancreatic and lung NETs and discusses the limitations of these
      tests and the potential role of newer multianalyte markers for NET management.

PMID- 28760233
TI  - Biochemical and Imaging Diagnostics in Endocrinology: Predictors of Fertility.
AB  - One of the limiting factors of fertility testing is the relative inefficiency of
      human reproduction. A careful history and physical examination must be performed
      on each patient to inform the particular diagnostic tests that are chosen and to
      create a meaningful treatment plan. Testing parameters, such as sensitivity,
      specificity, positive predictive value, and negative predictive value, can help
      to interpret test results, although there is no perfect screening test for the
      various causes of infertility. This article describes the 4 major categories of
      testing for infertility: ovarian reserve, ovulatory status, gamete transport, and
      male factor.

PMID- 28760234
TI  - Thyroid Cancer: Ultrasound Imaging and Fine-Needle Aspiration Biopsy.
AB  - Ultrasound is critical in detection, diagnosis, and management of thyroid
      nodules. Ultrasound detection of regional nodal metastatic disease is based on
      abnormal nodal morphology rather than size and is critical to initial surgical
      and long-term management of thyroid cancer. Fine-needle aspiration biopsy is the
      gold standard for malignancy diagnosis in thyroid cancer. Thyroglobulin assay of
      nodal aspirates improves accuracy in diagnosis of metastases. Reporting lexicons
      assign risk levels to thyroid nodules with the goal of improving and
      standardizing patient management. Surveillance ultrasound in papillary
      microcarcinomas is being evaluated and compared with surgical management.

PMID- 28760235
TI  - Pituitary Imaging.
AB  - Modern pituitary imaging is MRI. However, computed tomography (CT) still has
      limited usefulness. In addition, because CT offers much better bone detail and
      calcium detection, there are some cases in which such additional information is
      necessary. Before the advent of CT, plain radiography, pneumoencephalography, and
      angiography were used to diagnose pituitary masses. More recently, CT, and then
      especially MRI, made it possible to primarily delineate lesions within and around
      the pituitary gland rather than depend on secondary information that could only
      suggest their presence.

PMID- 28760230
TI  - Biochemical Testing in Thyroid Disorders.
AB  - This article summarizes the main principles for the appropriate use of laboratory
      testing in the diagnosis and management of thyroid disorders, as well as
      controversies that have arisen in association with some of these biochemical
      tests. To place a test in perspective, its sensitivity and accuracy should be
      taken into account. Ordering the correct laboratory tests facilitates the early
      diagnosis of a thyroid disorder and allows for timely and appropriate treatment.
      This article focuses on a comprehensive update regarding thyroid-stimulating
      hormone, thyroxine/triiodothyronine, thyroid autoantibodies, thyroglobulin, and
      calcitonin. Clinical uses of these biochemical tests are outlined.

PMID- 28760236
TI  - Adrenal Imaging.
AB  - Cross-sectional imaging can make a specific diagnosis in lesions, such as
      myelolipomas, cysts, and hemorrhage, and is often sufficient to distinguish
      benign from malignant adrenal processes. CT and MRI are useful studies to
      identify pheochromocytomas and cortisol-secreting or androgen-secreting tumors.
      In patients with primary aldosteronism, adrenal venous sampling remains the most
      accurate localizing study and should be performed in all patients older than 35.
      Radiolabeled isotope studies serve as second-line diagnostic tests for malignant
      adrenal tumors, primary or metastatic, as well as for pheochromocytoma. Nuclear
      imaging studies should follow a robust hormonal diagnosis and be correlated with
      findings on cross-sectional imaging.

PMID- 28760237
TI  - Pancreatic Imaging.
AB  - Imaging of the endocrine pancreas is dominated by neuroendocrine tumors, a
      diverse category of neoplasms that may or may not cause symptoms from hormone
      hypersecretion. These tumors may also be evidence of several different genetic
      syndromes. Understanding the usefulness of different imaging modalities and
      entities that simulate neuroendocrine tumors is key for both radiologists and
      referring physicians.

PMID- 28760238
TI  - Selected Controversies of Radioiodine Imaging and Therapy in Differentiated
      Thyroid Cancer.
AB  - This article discusses the more controversial areas of the management of
      differentiated thyroid cancer, namely, the utility of pretherapy staging
      radioiodine scans; the prescribed activity for iodine-131 remnant ablation,
      adjuvant treatment, and distant metastases; preparation with thyroid hormone
      withdrawal versus recombinant human thyroid-stimulating hormone; and the
      classification of radioiodine refractory differentiated thyroid cancer. The
      author reviews various aspects of the controversies, such as the recommendations
      of the 2015 guidelines of the American Thyroid Association, arguments for and
      against the various controversies, and selected references.

PMID- 28760239
TI  - Imaging of Neuroendocrine Tumors: Indications, Interpretations, Limits, and
      Pitfalls.
AB  - Imaging is critical in the diagnosis, prognosis, and management of neuroendocrine
      tumors (NETs). NETs share common imaging features, but each type exhibits unique
      features. Computed tomography scans or MRI of the abdomen is used to assess tumor
      burden routinely. Functional imaging with octreotide scan or gallium-68
      somatostatin analog PET is used selectively to confirm diagnosis and guide
      therapy. Clinicians and radiologists should be familiar with the indications and
      interpretations of imaging modalities. Novel functional imaging modalities likely
      will be developed to detect small NETs, predict prognosis, guide therapeutic
      choices, and design novel therapies.

PMID- 28760240
TI  - Latest Innovations in Biochemical and Imaging Diagnostics in Endocrinology.

PMID- 28760241
TI  - The Current Status and Evolution of Hormone Testing in the Digital Age.

PMID- 28760242
TI  - From the Editor.

PMID- 28760244
TI  - Erratum.

PMID- 28760245
TI  - Hymenoplasty and Muslim Patients: Islamic Ethico-Legal Perspectives.
AB  - BACKGROUND: Hymenoplasty, commonly called "revirginization," is a controversial
      procedure that pushes the scope of medical practice to satisfy cultural and/or
      religious "needs." AIM: To outline the sociocultural contexts underlying patient
      requests for hymenoplasty and present Islamic juridical views on the moral status
      of hymenoplasty for Muslim patients. METHODS: Narrative review of the extant
      bioethics literature and leading Islamic ethico-legal verdicts. OUTCOMES: We
      identified "Western" and Islamic bioethical debates on hymenoplasty and the
      critical concepts that underpin ethical justifications for and against the
      procedure. RESULTS: From a Western-ethics perspective, the life-saving potential
      of the procedure is weighed against the role of the surgeon in directly assisting
      in a deception and in indirectly promoting cultural practices of sexual
      inequality. From an Islamic bioethical vantage point, jurists offer two opinions.
      The first is that the surgery is always impermissible. The second is that
      although the surgery is generally impermissible, it can become licit when the
      risks of not having postcoital bleeding harm are sufficiently great. CLINICAL
      IMPLICATIONS: Patient requests for hymenoplasty should be approached by surgeons
      with a willingness to understand patients' social contexts and reasons for
      pursuing the procedure and are ethically justified by leading Islamic jurists in
      particular circumstances. STRENGTHS AND LIMITATIONS: This article presents emic
      and etic perspectives on hymenoplasty in Muslim patients, although our review of
      the Islamic bioethical stances might have missed some juridical opinions and
      important considerations. Further, Muslims, even devout ones, might not be
      beholden to Islamic juridical views on medical procedures and thus physicians
      should not make assumptions about the rationale for, and ethical views of,
      patients seeking hymenoplasty. CONCLUSION: This article provides critical insight
      into how Muslim patients, and Islamic jurists, evaluate the moral contexts of
      hymenoplasty. Bawany MH, Padela AI. Hymenoplasty and Muslim Patients: Islamic
      Ethico-Legal Perspectives. J Sex Med 2017;14:1003-1010.

PMID- 28760243
TI  - Comparative efficacy of beta-blockers on mortality and cardiovascular outcomes in
      patients with hypertension: a systematic review and network meta-analysis.
AB  - The differential efficacy of lipophilic and hydrophilic beta-blockers on clinical
      outcomes has not been investigated. We sought to compare the effects of
      lipophilic and hydrophilic beta-blockers on mortality and cardiovascular outcomes
      by conducting a comprehensive systematic review and network meta-analysis.
      MEDLINE/PubMed, EMBASE, and the Cochrane Database were searched for all dates to
      January 5, 2015, for randomized trials with comparisons between all beta-blockers
      or between beta-blockers and other antihypertensive agents. Mortality and
      cardiovascular outcomes were also reported. Characteristics of each study and
      associated clinical outcomes were extracted, including all-cause mortality,
      coronary heart disease, stroke, and cardiovascular death. Thirteen trials with
      90,935 participants were included, focusing on lipophilic beta-blockers
      (metoprolol, propranolol, and oxprenolol) and a hydrophilic beta-blocker
      (atenolol). In this review, lipophilic beta-blockers showed a significant
      reduction for the risk of cardiovascular mortality (odds ratio [OR] 0.72, 95%
      confidence interval [CI; 0.54-0.97]) compared with hydrophilic beta-blocker, and
      lipophilic beta-blockers showed decreased trend for the risk of all-cause
      mortality (OR 0.86, 95% CI [0.72-1.03]) and coronary heart disease (OR 0.88, 95%
      CI [0.64-1.23]). When the risk of stroke was evaluated using age stratification,
      lipophilic beta-blockers showed a significant reduction in the risk of stroke (OR
      0.63, 95% CI [0.41-0.99]) compared with hydrophilic beta-blocker in patients aged
      <65 years.

PMID- 28760246
TI  - Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and
      Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile
      Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial.
AB  - BACKGROUND: Phosphodiesterase type 5 inhibitors and alpha-adrenergic blocking
      agents (alpha-blockers) are widely used for the treatment of erectile dysfunction
      (ED) and lower urinary tract symptoms (LUTS) associated with benign prostatic
      hyperplasia (BPH). AIMS: To assess the efficacy and safety of fixed-dose
      combinations (FDCs) of tamsulosin and tadalafil compared with tadalafil
      monotherapy in patients with comorbid BPH-associated LUTS and ED. METHODS: A
      randomized, double-blinded, active-controlled trial was conducted of 510 men with
      BPH-associated LUTS and ED. Patients were treated with FDCs of tamsulosin 0.4 mg
      plus tadalafil 5 mg (FDC 0.4/5 mg), tamsulosin 0.2 mg plus tadalafil 5 mg (FDC
      0.2/5 mg), or tadalafil 5 mg for a 12-week treatment period. For a subsequent 12
      week extension period, the patients were administered FDC 0.4/5 mg. OUTCOMES: The
      primary outcomes were changes from baseline in total International Prostate
      Symptom Score (IPSS) and International Index of Erectile Function erectile
      function domain (IIEF-EF) score at week 12 to prove superiority and non
      inferiority of FDCs compared with tadalafil 5 mg. The safety assessments were
      adverse reactions, laboratory test results, and vital signs at week 24. RESULTS:
      The mean changes in total IPSS and IIEF-EF scores were -9.46 and 9.17 for FDC
      0.4/5 mg and -8.14 and 9.49 for tadalafil 5 mg, respectively, which indicated
      superiority in LUTS improvement (P = .0320) and non-inferiority in ED treatment
      with FDC 0.4/5 mg compared with tadalafil 5 mg. However, the results from FDC
      0.2/5 mg failed to demonstrate superiority in LUTS improvement. No clinically
      significant adverse events regarding the investigational products were observed
      during the 24-week period. CLINICAL IMPLICATIONS: The FDC 0.4/5 mg is the first
      combined formulation of an alpha-blocker and a phosphodiesterase type 5 inhibitor
      that offers benefits in patient compliance and as add-on therapy in patients with
      comorbid BPH-associated LUTS and ED. STRENGTHS AND LIMITATIONS: The study clearly
      demonstrated the advantage of FDC 0.4/5 mg. The main advantage of FDC 0.4/5 mg
      was the enhanced efficacy on BPH-associated LUTS comorbidity with ED, the lower
      incidence of side effects, and the simplification and convenience of therapy,
      which led to better overall patient compliance. However, the lack of a tamsulosin
      monotherapy control group was a limitation of this study. CONCLUSION: The FDC
      0.4/5 mg therapy was safe, well tolerated, and efficacious, indicating that
      combination therapy could provide clinical benefits for patients with BPH
      associated LUTS complaints and ameliorate the comorbidity of ED. Kim SW, Park NC,
      Lee SW, et al. Efficacy and Safety of a Fixed-Dose Combination Therapy of
      Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and
      Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled
      Trial. J Sex Med 2017;14:1018-1027.

PMID- 28760247
TI  - Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire
      Short Form (HIS-Q-SF).
AB  - BACKGROUND: The Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q
      SF) is a patient-reported outcome measurement designed to evaluate the symptoms
      of hypogonadism. The HIS-Q-SF is an abbreviated version including17 items from
      the original 28-item HIS-Q. AIM: To conduct item analyses and reduction, evaluate
      the psychometric properties of the HIS-Q-SF, and provide guidance on score
      interpretation. METHODS: A 12-week observational longitudinal study of
      hypogonadal men was conducted as part of the original HIS-Q psychometric
      evaluation. Participants completed the original HIS-Q every 2 weeks. Blood
      samples were collected to evaluate testosterone levels. Participants completed
      the Aging Male's Symptoms Scale, the International Index of Erectile Function,
      the Short Form-12, and the PROMIS Sexual Activity, Satisfaction with Sex Life,
      Sleep Disturbance, and Applied Cognition Scales (baseline and weeks 6 and 12).
      Clinicians completed the Clinical Global Impression of Severity and Change scales
      and a clinical form. MAIN OUTCOME MEASURES: Item performance was evaluated using
      descriptive statistics and Rasch analyses. Reliability (internal consistency and
      test-retest), validity (concurrent and know groups), and responsiveness were
      assessed. RESULTS: One hundred seventy-seven men participated (mean age = 54.1
      years, range = 23-83). Similar to the full HIS-Q, the final abbreviated HIS-Q-SF
      instrument includes five domains (sexual, energy, sleep, cognition, and mood)
      with two sexual subdomains (libido and sexual function). For key domains, test
      retest reliability was very good, and construct validity was good for all
      domains. Known-groups validity was demonstrated for all domain scores, subdomain
      scores, and total score based on the Clinical Global Impression-Severity. All
      domains and subdomains were responsive to change based on patient-rated anchor
      questions. CLINICAL IMPLICATIONS: The HIS-Q-SF could be a useful tool in clinical
      practice, epidemiologic studies, and other academic research settings. STRENGTHS
      AND LIMITATIONS: Careful consideration was given to the selection of the final
      HIS-Q-SF items based on quantitative data and clinical expert feedback. Overall,
      the reduced set of items demonstrated strong psychometric properties.
      Testosterone levels for the participating men were not as low as anticipated,
      which could have limited the ability to examine the relations between the HIS-Q
      SF and testosterone levels. Further, the analyses used data collected through
      administration of the full HIS-Q, and future studies should administer the
      standalone HIS-Q-SF to replicate the psychometric analyses reported in the
      present study. CONCLUSION: Similar to the original HIS-Q, the HIS-Q-SF has
      evidence supporting reliability, validity, and responsiveness. The short form
      includes a smaller set of items that might be more suitable for use in clinical
      practice or academic research settings. Gelhorn HL, Roberts LJ, Khandelwal N, et
      al. Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire
      Short Form (HIS-Q-SF). J Sex Med 2017;14:1046-1058.

PMID- 28760248
TI  - Are Surgical Residents Prepared for Fellowship Training in Gender-Confirming
      Surgery?

PMID- 28760249
TI  - Response to Letter to the Editor: "Gender Confirmation Surgery: Guiding
      Principles".

PMID- 28760250
TI  - Erratum.

PMID- 28760251
TI  - Erratum.

PMID- 28760252
TI  - Erratum.

PMID- 28760253
TI  - Erratum.

PMID- 28760254
TI  - Erratum.

PMID- 28760255
TI  - Erratum.

PMID- 28760256
TI  - Malleable vs Inflatable Implant? Which One to Choose.

PMID- 28760257
TI  - A Historical Review of Gender-Affirming Medicine: Focus on Genital Reconstruction
      Surgery.
AB  - Gender dysphoria (Diagnostic and Statistical Manual of Mental Disorders, Fifth
      Edition) is characterized by a marked discrepancy between one's birth-assigned
      sex and one's gender identity and is sometimes addressed by gender-affirming
      surgery. As public visibility and institutional support for the transgender and
      gender non-conforming population continue to increase, the demand for competent
      multidisciplinary teams of medical professionals equipped to care for this
      population is expected to rise-including plastic surgeons, urologists,
      gynecologists, endocrinologists, and breast surgeons, among others. Genital
      reconstruction procedures for the male-to-female and female-to-male transgender
      patient present unique surgical challenges that continue to evolve from their
      respective origins in the 19th and 20th centuries. A historical review of
      surgical techniques and standards of care attendant to gender-affirming medicine
      is presented, with foremost emphasis placed on how techniques for genital
      reconstruction in particular continue to evolve and advance. In addition, the
      current status of transition-related health care in the United States, including
      research gaps and contemporary clinical challenges, is reviewed. Frey JD,
      Poudrier G, Thomson JE, Hazen A. A Historical Review of Gender-Affirming
      Medicine: Focus on Genital Reconstruction Surgery. J Sex Med 2017;14:991-1002.

PMID- 28760259
TI  - Closing the door to ventricular tachycardia: Are we there yet?

PMID- 28760258
TI  - Cardiac magnetic resonance-aided scar dechanneling: Influence on acute and long
      term outcomes.
AB  - BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR)
      provides tissue characterization of ventricular myocardium and scar that can be
      depicted as pixel signal intensity (PSI) maps. OBJECTIVE: To assess the possible
      benefit of guiding the ventricular tachycardia (VT) substrate mapping by
      integrating these PSI maps into the navigation system. METHODS: In total, 159
      consecutive patients (66 +/- 11 years old, 151 men [95%]) with scar-related left
      ventricular (LV) VT were included. VT substrate ablation used the scar
      dechanneling technique. A CMR-aided ablation using the PSI maps was performed in
      54 patients (34%). Procedural data as well as acute and long-term outcomes were
      compared with those of the remaining 105 patients (66%). RESULTS: Mean procedure
      duration and fluoroscopy time were 229 +/- 67 minutes and 20 +/- 9 minutes,
      respectively, without significant differences between groups. Both the number of
      radiofrequency (RF) applications and RF delivery time were lower in the CMR-aided
      group (28 +/- 18 applications vs 36 +/- 18 applications, P = .037, and 19 +/- 12
      minutes vs 27 +/- 16 minutes, P = .009, respectively). After substrate ablation,
      monomorphic VT inducibility was lower in the CMR-aided than in the control group
      (17 [32%] vs 53 [51%] patients, P = .022). After a mean follow-up period of 20 +/
      19 months, patients from the CMR-aided group had a lower recurrence rate than
      those in the control group (10 patients [18.5%] vs 46 patients [43.8%],
      respectively, P = .002; log-rank P = .017). Multivariate analysis found that CMR
      aided ablation (hazard ratio, 0.48 [95% Confirdence Interval (CI) 0.24-0.96], P =
      .037) was an independent predictor of recurrences. CONCLUSION: CMR-aided scar
      dechanneling is associated with a lower need for RF delivery, higher
      noninducibility rates after substrate ablation, and a higher VT-recurrence-free
      survival.

PMID- 28760260
TI  - One tachycardia initiating a different one in a 76-year-old woman.

PMID- 28760261
TI  - Corrigendum to "Relationship of angiotensin I-converting enzyme (ACE) and
      bradykinin B2 receptor (BDKRB2) polymorphism with diabetic nephropathy" [BBA -
      Molecular Basis of Disease Vol.1863/Iss.6(2017) 1264-1272].

PMID- 28760262
TI  - Corrigendum to "Disruption of calpain reduces lipotoxicity-induced cardiac injury
      by preventing endoplasmic reticulum stress" [Biochim. Biophy.Acta 1862 (11): 2023
      2033].

PMID- 28760263
TI  - Time series analysis and mortality model of dog bite victims presented for
      treatment at a referral clinic for rabies exposure in Monrovia, Liberia, 2010
      2013.
AB  - We developed time trend model, determined treatment outcome and estimated annual
      human deaths among dog bite victims (DBVs) from 2010 to 2013 in Monrovia,
      Liberia. Data obtained from clinic records included victim's age, gender and site
      of bite marks, site name of residence of rabies-exposed patients, promptness of
      care sought, initial treatment and post-exposure-prophylaxis (PEP) compliance. We
      computed DBV time-trend plot, seasonal index and year 2014 case forecast.
      Associated annual human death (AHD) was estimated using a standardized decision
      tree model. Of the 775 DBVs enlisted, care seeking time was within 24h of injury
      in 328 (42.32%) DBVs. Victim's residential location, site of bite mark, and time
      dependent variables were significantly associated with treatment outcome (p<
      0.05). The equation X^t=28.278-0.365t models the trend of DBVs. The high (n=705,
      90.97%) defaulted PEP and average 155 AHD from rabies implied urgent need for
      policy formulation on national programme for rabies prevention in Liberia.

PMID- 28760264
TI  - Modeling spatio-temporal variations of substance abuse mortality in Iran using a
      log-Gaussian Cox point process.
AB  - Substance use disorder is one of the main mental health problems in Iran. In this
      paper, the six-monthly counts of deaths due to substance abuse in Iran at
      provincial level between March 21, 2005, and March 20, 2014, were modeled using a
      log-Gaussian Cox point process model. By assuming population density as the
      exposure variable, the considered model incorporated known and unknown
      influential factors in order to describe spatio-temporal variations in the
      relative risk of substance abuse mortality. We found evidence of spatial
      heterogeneity and inequality by gender in deaths related to substance abuse
      across Iran. This study provides the first evidence in Iran on the spatio
      temporal heterogeneity in mortality caused by substance use disorders.

PMID- 28760265
TI  - Modelling malaria incidence by an autoregressive distributed lag model with
      spatial component.
AB  - The influence of climatic variables on the dynamics of human malaria has been
      widely highlighted. Also, it is known that this mosquito-borne infection varies
      in space and time. However, when the data is spatially incomplete most popular
      spatio-temporal methods of analysis cannot be applied directly. In this paper, we
      develop a two step methodology to model the spatio-temporal dependence of malaria
      incidence on local rainfall, temperature, and humidity as well as the regional
      sea surface temperatures (SST) in the northern coast of Venezuela. First, we fit
      an autoregressive distributed lag model (ARDL) to the weekly data, and then, we
      adjust a linear separable spacial vectorial autoregressive model (VAR) to the
      residuals of the ARDL. Finally, the model parameters are tuned using a Markov
      Chain Monte Carlo (MCMC) procedure derived from the Metropolis-Hastings
      algorithm. Our results show that the best model to account for the variations of
      malaria incidence from 2001 to 2008 in 10 endemic Municipalities in North-Eastern
      Venezuela is a logit model that included the accumulated local precipitation in
      combination with the local maximum temperature of the preceding month as positive
      regressors. Additionally, we show that although malaria dynamics is highly
      heterogeneous in space, a detailed analysis of the estimated spatial parameters
      in our model yield important insights regarding the joint behavior of the disease
      incidence across the different counties in our study.

PMID- 28760266
TI  - Comparing multilevel and multiscale convolution models for small area aggregated
      health data.
AB  - In spatial epidemiology, data are often arrayed hierarchically. The
      classification of individuals into smaller units, which in turn are grouped into
      larger units, can induce contextual effects. On the other hand, a scaling effect
      can occur due to the aggregation of data from smaller units into larger units. In
      this paper, we propose a shared multilevel model to address the contextual
      effects. In addition, we consider a shared multiscale model to adjust for both
      scale and contextual effects simultaneously. We also study convolution and
      independent multiscale models, which are special cases of shared multilevel and
      shared multiscale models, respectively. We compare the performance of the models
      by applying them to real and simulated data sets. We found that the shared
      multiscale model was the best model across a range of simulated and real
      scenarios as measured by the deviance information criterion (DIC) and the
      Watanabe Akaike information criterion (WAIC).

PMID- 28760268
TI  - Comparison of survival time and comfort between 2 clear overlay retainers with
      different thicknesses.

PMID- 28760267
TI  - Common errors observed at the American Board of Orthodontics clinical
      examination.
AB  - The American Board of Orthodontics has developed tools to help examinees select
      patients to be used for the Board examination. The Case Management Form can be
      used to evaluate aspects of a patient's treatment that cannot be measured by
      other tools. The Case Management Form is a structured treatment-neutral
      assessment of orthodontic objectives and outcomes associated with a patient's
      treatment. Despite the availability of this form, examiners continue to see
      problems, including lack of attention to finishing details, inappropriate
      treatment objectives, excessive proclination of mandibular incisors due to
      treatment mechanics, excessive expansion of mandibular intercanine width, closing
      skeletal open bite with extrusion of anterior teeth leading to excessive gingival
      display, and failure to recognize the importance of controlling the eruption or
      extrusion of molars during treatment. In addition, some examinees exhibit a lack
      of understanding of proper cephalometric tracing and superimposition techniques,
      which lead to improper interpretation of cephalometric data and treatment
      outcomes.

PMID- 28760269
TI  - Authors' response.

PMID- 28760270
TI  - Transport distraction osteogenesis combined with orthodontic treatment.

PMID- 28760271
TI  - Authors' response.

PMID- 28760272
TI  - Authors' response.

PMID- 28760273
TI  - Bisphenol A in orthodontic adhesives.

PMID- 28760274
TI  - CBCT imaging vs conventional radiography.

PMID- 28760276
TI  - Courtesy counts.

PMID- 28760277
TI  - Randomized controlled trial of a patient decision-making aid for orthodontics.
AB  - INTRODUCTION: Patient decision-making aids (PDAs) are instruments that facilitate
      shared decision making and enable patients to reach informed, individual
      decisions regarding health care. The objective of this study was to assess the
      efficacy of a PDA compared with traditional information provision for adolescent
      patients considering fixed appliance orthodontic treatment. METHODS: Before
      treatment, orthodontic patients were randomly allocated into 2 groups: the
      intervention group received the PDA and standard information regarding fixed
      appliances, and the control group received the standard information only.
      Decisional conflict was measured using the Decisional Conflict Scale, and the
      levels of decisional conflict were compared between the 2 groups. RESULTS:
      Seventy-two patients were recruited and randomized in a ratio of 1:1 to the PDA
      and control groups. Seventy-one patients completed the trial (control group, 36;
      PDA group, 35); this satisfied the sample size calculation. The median total
      Decisional Conflict Scale score in the PDA group was lower than in the control
      group (15.63 and 19.53, respectively). However, this difference was not
      statistically significant (difference between groups, 3.90; 95% confidence
      interval of the difference, -4.30 to 12.11). Sex, ethnicity, age, and the time
      point at which patients were recruited did not have significant effects on
      Decisional Conflict Scale scores. No harm was observed or reported for any
      participant in the study. CONCLUSIONS: The results of this study showed that the
      provision of a PDA to adolescents before they consented for fixed appliances did
      not significantly reduce decisional conflict. There may be a benefit in providing
      a PDA for some patients, but it is not yet possible to say how these patients
      could be identified. REGISTRATION: This trial was registered with the Harrow
      National Research Ethics Committee (reference 12/LO/0279). PROTOCOL: The protocol
      was not published before trial commencement.

PMID- 28760278
TI  - Individualized intervention to reduce anxiety in adult orthodontic patients based
      on Q methodology.
AB  - INTRODUCTION: In this study, we used Q methodology to assess the concerns of
      adults seeking orthodontic treatment and to determine individualized
      interventions to reduce their anxiety. METHODS: Statements of concern were
      derived by in-depth interviews with 70 adult patients. Q sorting methodology was
      then used to identify the main factors associated with anxiety in a cohort of 40
      adults who had not been involved in the first part of the study. The final stage
      involved a randomized study in which 160 new adult patients were recruited and
      randomized into intervention and control groups. Participants in the intervention
      group sorted the statements, after which individualized interventions were
      implemented. Participants in the control group received routine treatment. The
      State-Trait Anxiety Inventory was used to measure changes in participants'
      anxiety levels before and during treatment. RESULTS: In total, 41 statements were
      identified, and participants were classified according to 5 factors. Factor 1
      participants were concerned about the lack of treatment information; factor 2
      represented concerns about cost and other people's opinions; factor 3 represented
      concerns about impact on work related to wearing braces; factor 4 encompassed
      concerns about treatment effects, pain, and dental fears; and factor 5 reflected
      concerns about side effects and finding a partner. The mean state anxiety
      inventory scores for both the intervention and control groups were highest 24
      hours after bonding (intervention group, 44.63 +/- 4.49; control group, 49.43 +/-
      5.42). The intragroup state anxiety inventory scores differed significantly
      across the 6 time points (P <0.01), with the state anxiety inventory scores of
      the intervention group significantly lower than those of the control group (P
      <0.01) at all time points except baseline. No significant intergroup or
      intragroup differences were found in relation to trait anxiety. CONCLUSIONS:
      Adult orthodontic patients expressed diverse concerns. Individualized
      interventions based on Q methodology may reduce anxiety in this patient
      population.

PMID- 28760279
TI  - Risk factors for tobacco susceptibility in an orthodontic population: An
      exploratory study.
AB  - INTRODUCTION: Tobacco use is related to increased periodontal disease, tooth
      loss, and decreased success of orthodontic appliances, and it may inhibit
      orthodontic tooth movement. Most smokers start during adolescence. Since most
      cessation attempts fail, prevention appears necessary. METHODS: A cross-sectional
      sample of orthodontic patients reported hypothesized risk factors for smoking and
      susceptibility to tobacco use initiation. Exploratory analyses regressed
      susceptibility to tobacco initiation on each hypothesized predictor variable in a
      separate logistic model that included a standard set of covariates. RESULTS:
      Significant odds ratios (OR) were found for the presence of a smoker in the home
      (OR, 2.168; 95% confidence interval [CI], 1.144-4.107), a friend having no
      smoking rules in his or her home and car (OR, 0.337; 95% CI, 0.128-0.886), having
      been offered a cigarette (OR, 4.526; 95% CI, 1.190-17.207), and exposure to
      tobacco advertisements (OR, 1.910; 95% CI, 1.044-3.496). CONCLUSIONS: Peer,
      family, and environmental factors appear to increase children's susceptibility to
      smoking in orthodontic populations. Attention to such factors could help dental
      clinicians to more effectively identify susceptible young patients in need of
      antismoking advice. Prospective and experimental studies are required to confirm
      the role that dental clinicians might play in youth smoking prevention.

PMID- 28760280
TI  - Effects of Case Western Reserve University's transverse analysis on the quality
      of orthodontic treatment.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effect of using the
      transverse analysis developed at Case Western Reserve University (CWRU) in
      Cleveland, Ohio. The hypotheses were based on the following: (1) Does following
      CWRU's transverse analysis improve the orthodontic results? (2) Does following
      CWRU's transverse analysis minimize the active treatment duration? METHODS: A
      retrospective cohort research study was conducted on a randomly selected sample
      of 100 subjects. The sample had CWRU's analysis performed retrospectively, and
      the sample was divided according to whether the subjects followed what CWRU's
      transverse analysis would have suggested. The American Board of Orthodontics
      discrepancy index was used to assess the pretreatment records, and quality of the
      result was evaluated using the American Board of Orthodontics cast/radiograph
      evaluation. The Mann-Whitney test was used for the comparison. RESULTS: CWRU's
      transverse analysis significantly improved the total cast/radiograph evaluation
      scores (P = 0.041), especially the buccolingual inclination component (P =
      0.001). However, it did not significantly affect treatment duration (P = 0.106).
      CONCLUSIONS: CWRU's transverse analysis significantly improves the orthodontic
      results but does not have significant effects on treatment duration.

PMID- 28760281
TI  - Prediction of long-term success of orthopedic treatment in skeletal Class III
      malocclusions.
AB  - INTRODUCTION: We investigated the long-term success of orthopedic treatment in
      skeletal Class III malocclusions, established a model to predict its long-term
      success, and verified previously reported success rates and prediction models.
      METHODS: Fifty-nine patients who underwent successful facemask treatment and were
      followed until growth completion were evaluated. After completion of growth, the
      patients were divided into successful and unsuccessful groups according to
      overjet, overbite, and facial profile. Pretreatment cephalometric measurements
      were compared between groups, and logistic regression analysis was used to
      identify the predictors of long-term success. Four previously published articles
      were selected to verify the success rate and predictability of the prediction
      models with regard to our patient sample. RESULTS: The treatment success rate was
      62.7%. The AB-mandibular plane angle, Wits appraisal, and the articular angle
      were identified as predictors. The success rates differed according to success
      criteria and patient characteristics. The prediction models proposed by the 4
      previous studies and our study showed similar predictabilities (61.0%-64.4%) for
      our patient sample. The predictability for the unsuccessful group was low.
      CONCLUSIONS: Our results suggest that no particular method or factor can predict
      the long-term success of orthopedic treatment for skeletal Class III
      malocclusion.

PMID- 28760282
TI  - Rate of tooth movement and dentoskeletal effects of rapid canine retraction by
      dentoalveolar distraction osteogenesis: A prospective study.
AB  - INTRODUCTION: The purpose of this study was to test the null hypothesis that
      duration of orthodontic treatment can be significantly reduced by accelerating
      canine retraction using dentoalveolar distraction (DAD). METHODS: Thirty-six
      maxillary canines of 19 patients comprised the DAD group, and 28 canines of 14
      patients were included in the distalization group (DG). The initial mean ages
      were 15.8 +/- 1.96 years for the DAD group and 16.02 +/- 2.8 years for the DG. A
      custom-made, rigid, tooth-borne intraoral distraction device was used for the DAD
      group, and intraoral elastics were applied for canine distalization in the DG.
      Six skeletal and 11 dental variables were measured for the cephalometric
      evaluation. RESULTS: Canine retraction was 7.9 +/- 1.49 mm in 11.8 +/- 1.3 days
      and canine distal tipping was 11.48 degrees  +/- 4.37 degrees  after DAD; the
      canines were distalized 5.29 +/- 2.01 mm and tipped 13.64 degrees  +/- 9.54
      degrees  in 200 +/- 57 days in the DG. The rates of posterior canine movement
      were 0.67 +/- 0.14 mm per day after DAD and 0.03 +/- 0.01 mm per day in the DG.
      No significant first molar anchorage loss was observed after DAD, although the DG
      showed some vertical and sagittal first molar movement. CONCLUSIONS: We failed to
      reject the null hypothesis. DAD can reduce the duration of orthodontic treatment
      time by accelerating canine retraction in extraction patients without undesirable
      side effects.

PMID- 28760283
TI  - Idiopathic condylar resorptions: 3-dimensional condylar bony deformation, signs
      and symptoms.
AB  - INTRODUCTION: Our aim was to describe 3-dimensional condylar deformation of the
      temporomandibular joint (TMJ) and symptoms and signs of temporomandibular
      dysfunction (TMD) in patients with idiopathic condylar resorption (ICR). METHODS:
      We included 25 patients with ICR and 25 controls. We performed cone-beam computed
      tomographic scans and analyzed condylar width, length, and height as well as the
      condylar axial angle and the condylar neck angle. TMJ cross sections were
      evaluated for degenerative characteristics and location of bony deformations.
      Furthermore, symptoms and signs of TMD were described in the ICR group. RESULTS:
      In the ICR group, we found statistically significantly reduced condylar width
      (mean difference, 2.0 mm), height (mean difference, 4.9 mm), and condylar axial
      angle (mean difference, 10.6 degrees ); 84% of the TMJs had a posterior condylar
      neck angle (control group, 22%). The most common degenerative changes were
      noncongruent shape of the condyle-fossa relationship (72%), condylar resorption
      (56%), and nonintact cortex (40%). More than 70% of the joints with bony
      deformations showed changes along the entire condylar head. Most patients with
      ICR showed symptoms and signs of TMD; nevertheless, 12% had no signs or symptoms
      of TMD. CONCLUSIONS: ICR in the TMJ changes the shape and reduces the size of the
      condyle. Deformity locations are unspecified, and the entire condyle is often
      affected. Most patients with ICR have signs or symptoms of TMD; however, a small
      group was asymptomatic and without clinical signs.

PMID- 28760284
TI  - Prognosis of primary and secondary insertions of orthodontic miniscrews: What we
      have learned from 500 implants.
AB  - INTRODUCTION: Although the success of using orthodontic miniscrews for primary
      insertion has been reported in the literature, few studies have followed up on
      secondary insertions after failure of the first insertion. In this study, we
      investigated not only the primary but also secondary success rates of miniscrews
      and considered the risk factors influencing their stability. METHODS: Five
      hundred miniscrews were inserted for orthodontic anchorage in 240 patients.
      Ninety-eight miniscrews lacked stability; thus, 77 of these were removed and
      reinserted. We calculated and compared the primary and secondary success rates of
      insertion. Moreover, we investigated which clinical parameters affected the
      stability of miniscrews. RESULTS: The success rate of secondary insertion (44.2%)
      was significantly lower than that of primary insertion (80.4%). The screw length
      and jaw receiving the insertion were significantly associated with the stability
      of miniscrews. The 8.0-mm miniscrews were significantly more stable than the 6.0
      mm miniscrews, and the success rate for insertions into the maxilla was
      significantly higher than that for the mandible. CONCLUSIONS: Secondary
      insertions lack stability; therefore, clinicians should be aware of the reduced
      success rate of reinsertion and know the risk factors to avoid failure of
      secondary insertions.

PMID- 28760285
TI  - Effects of unilateral premolar extraction treatment on the dental arch forms of
      Class II subdivision malocclusions.
AB  - INTRODUCTION: A retrospective study evaluating posttreatment symmetry in dental
      arch form and midlines was carried out in Class II subdivision patients treated
      with unilateral and bilateral maxillary premolar extractions. METHODS: Using
      Geomagic (version 14; Geomagic, Research Triangle Park, NC) and MATLAB (version
      8.4; MathWorks, Natick, Mass) software, best-fit curves expressed as quartic
      polynomials were generated for 13 Class II subdivisions treated with unilateral
      extractions and 20 treated with bilateral maxillary premolar extractions.
      Transverse and sagittal measurements were recorded to assess symmetry. Dental
      models were superimposed on constructed reference planes to generate average
      posttreatment arches. Statistical comparisons were performed with the
      significance level set at P <=0.05. RESULTS: The unilateral extraction group
      showed significant differences in transverse arch forms between the right and
      left sides in the anterior, anterior-middle, and middle segments of the arch, and
      all regions other than the posterior segment in the sagittal dimension.
      Significant differences were found between groups in the anterior and anterior
      middle segments of the arch transversely, the middle and middle-posterior
      segments sagittally, and the midline deviation relative to the midsagittal plane.
      Superimposed average arches showed similar results. CONCLUSIONS: Unilateral
      maxillary extraction treatment generally results in a narrower and more
      posteriorly displaced arch form on the extraction side, with a deviated maxillary
      midline toward the extraction side of the arch.

PMID- 28760286
TI  - Influence of different setups of the Frankfort horizontal plane on 3-dimensional
      cephalometric measurements.
AB  - INTRODUCTION: The Frankfort horizontal (FH) is a plane that intersects both
      porions and the left orbitale. However, other combinations of points have also
      been used to define this plane in 3-dimensional cephalometry. These variations
      are based on the hypothesis that they do not affect the cephalometric analysis.
      We investigated the validity of this hypothesis. METHODS: The material included
      cone-beam computed tomography data sets of 82 adult subjects with Class I molar
      relationship. A third-party method of cone-beam computed tomography-based 3
      dimensional cephalometry was performed using 7 setups of the FH plane. Six
      lateral cephalometric hard tissue measurements relative to the FH plane were
      carried out for each setup. Measurement differences were calculated for each pair
      of setups of the FH plane. The number of occurrences of differences greater than
      the limits of agreement was counted for each of the 6 measurements. RESULTS: Only
      3 of 21 pairs of setups had no occurrences for the 6 measurements. No measurement
      had no occurrences for the 21 pairs of setups. Setups based on left or right
      porion and both orbitales had the greatest number of occurrences for the 6
      measurements. CONCLUSIONS: This investigation showed that significant and
      undesirable measurement differences can be produced by varying the definition of
      the FH plane.

PMID- 28760287
TI  - Surgery-first orthognathic approach vs traditional orthognathic approach: Oral
      health-related quality of life assessed with 2 questionnaires.
AB  - INTRODUCTION: The purposes of the study were to investigate and evaluate the
      differences detected by the patients between the traditional orthognathic
      approach and the surgery-first one in terms of level of satisfaction and quality
      of life. METHODS: A total of 30 patients who underwent orthognathic surgery for
      correction of malocclusions were selected and included in this study. Fifteen
      patients were treated with the conventional orthognathic surgery approach, and 15
      patients with the surgery-first approach. Variables were assessed through the
      Orthognathic Quality of Life Questionnaire and the Oral Health Impact Profile
      questionnaire and analyzed with 2-way repeated-measures analysis of variance.
      RESULTS: The results showed significant differences in terms of the Orthognathic
      Quality of Life Questionnaire (P <0.001) and the Oral Health Impact Profile (P
      <0.001) scores within groups between the first and last administrations of both
      questionnaires. Differences in the control group between first and second
      administrations were also significant. Questionnaire scores showed an immediate
      increase of quality of life after surgery in the surgery-first group and an
      initial worsening during orthodontic treatment in the traditional approach group
      followed by postoperative improvement. CONCLUSIONS: This study showed that the
      worsening of the facial profile during the traditional orthognathic surgery
      approach decompensation phase has a negative impact on the perception of
      patients' quality of life. Surgeons should consider the possibility of a surgery
      first approach to prevent this occurrence.

PMID- 28760288
TI  - Surgery-first approach in correcting skeletal Class III malocclusion with
      mandibular asymmetry.
AB  - This case report describes a surgical orthodontic case that used the recently
      introduced surgery-first approach to correct a severe skeletal Class III
      malocclusion. A 19-year-old woman presented with severe mandibular prognathism
      and facial asymmetry; she had been waiting for growth completion in order to
      pursue surgical correction. After prediction of the postsurgical tooth movement
      and surgical simulation, 2-jaw surgery that included maxillary advancement and
      differential mandibular setback was performed using a surgery-first approach.
      Immediate facial improvement was achieved and postsurgical orthodontic treatment
      was efficiently carried out. The total treatment time was 16 months. The
      patient's facial appearance improved significantly and a stable surgical
      orthodontic outcome was obtained.

PMID- 28760289
TI  - Orthodontic-surgical retreatment of facial asymmetry with occlusal cant and
      severe root resorption: A 3-year follow-up.
AB  - Our objective was to report the orthodontic and surgical retreatment of a patient
      who had undergone a prolonged orthodontic treatment with extractions, but who had
      unsatisfactory results and persistent side effects. The man, aged 25 years 3
      months, sought treatment with major complaints of facial and smile asymmetries.
      The clinical examination showed a mandibular deviation to the right and a
      maxillary occlusal cant. A Class II Division 1 subdivision right was observed.
      Radiographic examination showed extensive root resorptions in the maxillary
      second premolars and absence of the 4 first premolars. The maxillary midline was
      deflected 2 mm to the left, and the mandibular midline was shifted 5 mm to the
      right. Aligning and leveling were performed with orthodontic fixed appliances,
      with a standard edgewise system (0.022 * 0.028 in), followed by LeFort I
      maxillary impaction and bilateral sagittal split osteotomy with asymmetrical
      advancement. Retreatment showed outstanding results that remained stable after 3
      years of follow-up. Root resorption in the second premolars did not seem to
      increase. Orthodontic-surgical intervention is the main choice for correcting
      esthetic and functional problems in facial asymmetry, particularly in cases of
      retreatment.

PMID- 28760290
TI  - Caught but released.

PMID- 28760291
TI  - Poisson regression.

PMID- 28760292
TI  - Proceedings of the Fourth Annual Meeting of the Society of Hematologic Oncology.

PMID- 28760293
TI  - Philadelphia-positive Acute Lymphoblastic Leukemia: Do We Still Need Allogeneic
      Transplantation? Argument "Pro".

PMID- 28760294
TI  - Management of Patients With Histologic Transformation.
AB  - The incidence of histological transformation is up to 30% over a period of 10
      years. This risk persists even beyond the initial decade of diagnosis of an
      indent lymphoma. In this era of emerging novel therapies, one could hope for an
      improved survival. There are currently no randomized trials guiding therapy for
      transformed lymphoma. Treatment recommendations are based on observational
      studies or non-randomized single arm clinical trials. To that extent, although
      routinely recommended and performed at transplant centers, voluminous evidence to
      suggest the timing or type (autologous or allogeneic) of transplant is lacking.
      In this article, we discuss the clinical features, treatment approach and role of
      stem cell transplant in transformed lymphoma.

PMID- 28760295
TI  - Diagnostic Challenges of Hemophagocytic Lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by excessive
      activation of the immune system, resulting in overproduction of inflammatory
      cytokines. Patients usually present with high fever, cytopenias,
      hyperferritinemia, and hepatosplenomegaly, and their disease process ranges from
      mild to fatal multiorgan failure. HLH is a heterogeneous group of disorders that
      can be triggered by infections, neoplasms, or autoimmune diseases. The HLH
      diagnosis can be difficult to confidently confirm in critically ill patients
      while waiting for pathology or reference laboratory results to return, delaying
      the diagnosis with significantly worsened outcomes. The current HLH-2004
      diagnostic guidelines were originally developed for pediatric cases and were not
      validated to diagnose secondary HLH, whether in children or adults. In addition,
      some laboratory findings that are common among HLH patients such as
      hypoalbuminemia and elevated liver enzymes are not represented in the HLH-2004
      guidelines. Even more challenging for clinicians is that many of the diagnostic
      features of this syndrome are nonspecific. For example, the clinical presentation
      of HLH can meet the diagnostic criteria of systemic inflammatory response
      syndrome, viral infections, or neoplastic diseases. It is necessary to revisit
      the diagnostic criteria for HLH by validating the clinical and laboratory
      findings in large prospective HLH prospective clinical trials or by establishing
      registries. This will improve our understanding of HLH, help validate and develop
      newer, more specific, and more rapidly obtainable diagnostic criteria, and,
      eventually, result in earlier therapy with more consistent monitoring of the
      response.

PMID- 28760296
TI  - Analysis of Survival of Patients with Chronic Myeloid Leukemia Treated with
      Imatinib in the Last 15 Years in Lebanon.
AB  - BACKGROUND: In the 2000s, the introduction of the tyrosine kinase inhibitor
      (TKI), imatinib, improved the survival outcomes of patients with chronic myeloid
      leukemia (CML). In Lebanon, we rapidly adopted this treatment strategy. To the
      best of our knowledge, this is the first study reporting the survival rates of
      Lebanese CML patients. We examined the rates of major molecular response (MMR)
      and complete cytogenetic response (CCyR) and analyzed the overall survival,
      progression-free survival, and event-free survival of CML patients treated with
      front-line imatinib in 3 university hospitals in Lebanon. PATIENTS AND METHODS:
      We retrospectively reviewed the medical records of 46 patients diagnosed with CML
      and treated with front-line imatinib 400 mg/day from 2000 and followed up to
      2015. In all patients, initially, 2 diagnostic tests were performed: cytogenetic
      analysis and qualitative molecular testing of the BCR-ABL transcript. The male-to
      female sex ratio was 3:1. The median age at diagnosis was 49 years, and the mean
      age was 44.52 years. At diagnosis, 46 patients were in the chronic phase. All
      patients started imatinib 400 mg/day. Of the 46 patients, 35 had a typical
      karyotype, 8 an atypical karyotype, and 3 hypoploidism. RESULTS: The MMR rate at
      18 months was 58.69%. The cumulative CCyR rate at 18 months of therapy with
      imatinib at the standard dose was 67.39%. The event-free survival rate was 75.86%
      and 74.14% at 5 and 8 years, respectively. The progression-free survival rate was
      77.59% and 75.86% at 5 and 8 years, respectively. The overall survival rate was
      98.27% and 98.27% at 5 and 8 years, respectively. Of the 46 patients, 12
      developed disease progression and were salvaged by second-generation TKIs. These
      12 patients were still alive with a MMR. CONCLUSION: In our study population, the
      achievement of a MMR and CCyR and overall survival, progression-free survival,
      and event-free survival were similar to previous published data. Reaching high
      survival rates with a first-generation TKI in a country with limited resources is
      a reasonable treatment approach for CML patients.

PMID- 28760297
TI  - Progress in Myelodysplastic Syndromes: Clinicopathologic Correlations and Immune
      Checkpoints.
AB  - BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal neoplasms
      characterized by ineffective hematopoiesis. Hypomethylating agent (HMA) therapy
      is one of the mainstays of MDS therapy. Failure of HMA therapy is related to poor
      outcome; hence, new therapeutic approaches are warranted in these patients. In
      MDS, the immune system has a pivotal role in modulation of hematopoiesis and
      clonal expansion. In neoplastic conditions, immune checkpoint (PD-1 and CTLA4
      molecules) hide tumor cells from immune surveillance. Identification of the
      pattern of expression of these molecules in MDS provides an interesting
      alternative within clinical trials. MATERIALS AND METHODS: We describe the
      clinicopathologic correlations by morphology, immunohistochemistry (PD-L1) and
      flow cytometry immunophenotypic analysis in an MDS patient treated with immune
      checkpoint PD-1 inhibitor. RESULTS: Bone marrow (BM) morphology, differential
      counts and aberrant flow markers were assessed before and after anti PD-1
      inhibitor therapy. At baseline, BM showed severe trilineage dysplasia with
      decreased granulopoiesis; after therapy, BM showed normal trilineage
      hematopoiesis. A decrease in PD-L1 expression, by manual and automatic analysis,
      was also noted from 15% to 5% after 26 months of treatment. The findings
      correlated with the recovery of peripheral blood counts and transfusion
      independency. CONCLUSION: BM morphology and PD-L1 expression by
      immunohistochemistry can be used to assess treatment response in immune
      checkpoints therapy.

PMID- 28760298
TI  - Minimal Residual Disease Assessment and Risk-based Therapy in Acute Lymphoblastic
      Leukemia.
AB  - The study of minimal residual disease (MRD) in adult patients with acute
      lymphoblastic leukemia (ALL) allows a greater refinement of the individual risk
      classification and is the best support for risk-specific therapy with or without
      allogeneic hematopoietic cell transplantation (HCT). Using case-specific
      sensitive molecular probes or multiparametric flow cytometry on marrow samples
      obtained from the end of induction until midconsolidation, MRD assays can detect
      up to 1 leukemic cell of 10,000 total mononuclear cells (sensitivity, 0.01%; ie,
      >=104). This cutoff, presently bound to technical limitations and subject to
      improvement, reflects the individual chemosensitivity and is strongly correlated
      with treatment outcome. The chance for cure is approximately 70% in the MRD
      negative subset but only 20% to 30% in MRD-positive patients, in any diagnostic
      and risk subset. As shown by prospective trials from Germany, Italy, Spain, and
      France-Switzerland-Belgium, approximately 50% to 70% of unselected adult patients
      with Philadelphia-negative ALL achieve and maintain an early MRD response,
      whereas the remainder do not, including a substantial proportion of clinically
      standard-risk patients, and require an HCT to avert at least partially the risk
      of relapse. Along with the diffusion of more effective "pediatric-inspired"
      chemotherapy programs, the MRD analysis is an integral part of a modern
      management strategy, guiding the decision process to transplant or not, in which
      case nonrelapse mortality using HCT in first remission-still 10% to 20%-is
      totally abolished. The use of new agents such as monoclonal antibodies, small
      inhibitors, and chimeric antigen receptor T cells is opening a new era of MRD
      directed therapies, that will further increase survival rates.

PMID- 28760299
TI  - Is Disease-Specific Immunotherapy a Potential Reality for MDS?
AB  - Myelodysplastic syndromes (MDSs) and related myeloid neoplasms represent
      heterogeneous diseases with overall poor outcomes related to lack of efficacious
      agents. Immunotherapy has revolutionized the treatment paradigm in solid
      malignancies and select hematologic malignancies with durable remissions in
      treatment-refractory populations. The initial clinical studies using
      immunotherapy in MDS are under way, although significant efforts are required in
      which to better understand their role in this disease. Likely, combinations of
      therapies will be required to improve outcomes in this patient population.
      Furthermore, identification of novel targets for antibody or T-cell modulation
      strategies is a matter of intensive investigation and ideally will provide
      treatment options in the near future for our patients.

PMID- 28760300
TI  - First-line Therapeutic Strategies for Myelodysplastic Syndromes.
AB  - The precise diagnostic tests and subsequent prognostic stratification for
      patients with myelodysplastic syndrome (MDS) are often cumbersome, yet they are
      the basis of successful therapy. Diverse treatment options are available for
      these patients; however, the decisions in real-life are often not grounded on the
      available evidence. Although the International Prognostic Scoring System and
      revised International Prognostic Scoring System are still driving the medical
      approach to MDS patients, additional variables must be considered when
      therapeutic intervention is needed. A rational scheme for first-line therapy is
      described that allows for the possibility of selecting the optimal individual
      therapy for MDS patients.

PMID- 28760301
TI  - The Challenge of Treating Myelodysplastic Syndromes/Myeloproliferative Neoplasms.
AB  - Myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) comprise a
      spectrum of myeloid disorders with both dysplastic and proliferative features,
      arising from hematopoietic stem cells. MDS/MPN are neither MDS nor MPN but a
      distinct World Health Organization-defined subclassification of diseases that, by
      definition, do not arise from a pre-existing MDS or MPN, inherently creating
      diagnostic and therapeutic challenges. Appropriately recognizing and classifying
      MDS/MPN is paramount for appropriately formulating treatment strategies and
      accurate prognostication. Highlighting the unique molecular, morphologic, and
      clinical characteristics among the subclassifications of MDS/MPN can assist in
      the appropriate diagnosis and aid in choice of therapeutic strategies. We
      describe the challenges of the appropriate diagnosis and treatment of MDS/MPN.

PMID- 28760304
TI  - Diagnostic, Prognostic, and Predictive Utility of Recurrent Somatic Mutations in
      Myeloid Neoplasms.
AB  - The classification and risk stratification of myeloid neoplasms, including acute
      myeloid leukemia, myelodysplastic syndromes, myelodysplastic
      syndromes/myeloproliferative neoplasms, and myeloproliferative neoplasms, have
      increasingly been guided by molecular genetic abnormalities. Gene expression
      analysis and next-generation sequencing have led to the ever increasing discovery
      of somatic gene mutations in myeloid neoplasms. Mutations have been identified in
      genes involved in epigenetic modification, RNA splicing, transcription factors,
      DNA repair, and the cohesin complex. These new somatic/acquired gene mutations
      have refined the classification of myeloid neoplasms and have been incorporated
      into the 2016 update of the World Health Organization (WHO) classification and
      the National Comprehensive Cancer Network guidelines. They have also been helpful
      in the development of new targeted therapeutic agents. In the present review, we
      describe the clinical utility of recently identified, clinically important gene
      mutations in myeloid neoplasms, including those incorporated in the 2016 update
      of the WHO classification.

PMID- 28760303
TI  - Analysis of Efficacy and Tolerability of Bruton Tyrosine Kinase Inhibitor
      Ibrutinib in Various B-cell Malignancies in the General Community: A Single
      center Experience.
AB  - BACKGROUND: Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK),
      is a novel drug that has shown significant efficacy and survival benefit for
      treatment of various B-cell malignancies. The primary objective of the present
      study was to investigate the efficacy of ibrutinib therapy in various B-cell
      malignancies in the general community. The secondary objectives included studying
      the adverse effects, ibrutinib-induced peripheral lymphocytosis, and effect on
      immunoglobulin levels. PATIENTS AND METHODS: The present study was a
      retrospective observational cohort analysis conducted at Abington Jefferson
      Health. The clinical response was determined from the hematologist's assessment
      and evaluated independently using the response criteria for each B-cell
      malignancy. Adverse effects were graded according to the Common Terminology
      Criteria for Adverse Events, version 4.0. The Wilcoxon signed-rank test was used
      to compare immunoglobulin levels before and after ibrutinib. Forty five patients
      with B-cell malignancies and receiving ibrutinib therapy were eligible. RESULTS:
      The median age was 73 years (range, 49-96 years), and 84.4% of the patients had
      received >= 1 previous therapy. The best overall response rate of all cohorts
      combined was 63.8%. The greatest overall response rate was observed in patients
      with chronic lymphocytic leukemia or small lymphocytic lymphoma (76.1%), followed
      by those with Waldenstrom macroglobulinemia (75%). Of the 45 patients, 88.9%
      experienced adverse effects. Antiplatelet activity of ibrutinib was most commonly
      observed (30.5%). Of note, 5 patients (11%) developed new-onset atrial
      fibrillation after drug initiation. Peripheral lymphocytosis after drug
      initiation was observed in most patients, with a peak level at 1 month (median
      lymphocyte count, 2.7 * 103 cells/MUL). Although the IgG levels at 3, 6, and 12
      months had decreased (P = .01 for all) compared with the levels before ibrutinib,
      the IgA levels had not increased at 3, 6, 12, and 24 months (P = .6, P = .5, P =
      .3, and P = .9, respectively). CONCLUSION: Ibrutinib is a highly effective and
      tolerable drug for B-cell malignancies in the general community. In contrast to
      the previously reported rate of 5% to 7%, we observed a higher rate (11%) of
      atrial fibrillation, which might have resulted from the smaller sample size in
      the present study and the multiple comorbidities. Nonetheless, this treatment
      limiting side effect requires further elucidation. Paradoxical lymphocytosis at
      the outset of therapy was a common and benign finding. In conjunction with the
      reported trials, the IgG levels decreased in the first year of continued therapy.
      However, the IgA levels did not increase, even after 2 years of therapy.

PMID- 28760302
TI  - Developmental Therapeutics in Myeloproliferative Neoplasms.
AB  - The unprecedented success of the Janus kinase (JAK) 1/2 inhibitor ruxolitinib in
      myelofibrosis (MF) provided much-needed impetus for clinical drug development for
      the Philadelphia chromosome-negative myeloproliferative neoplasms. The survival
      benefit conferred by this agent, along with its marked efficacy with regard to
      spleen volume and symptom reduction, have made ruxolitinib the cornerstone of
      drug therapy in MF. However, there remain significant unmet needs in the
      treatment of patients with MF, and many novel classes of agents continue to be
      investigated in efforts to build on the progress made with ruxolitinib. These
      include inhibitors of histone deacetylases (HDACs) and DNA methyltransferases,
      phosphatidylinositol-3-kinase isoforms, heat shock protein 90, cyclin-dependent
      kinases 4/6, and Hedgehog signaling, among others. In parallel, other JAK
      inhibitors with potential for less myelosuppression or even improvement of
      anemia, greater selectivity for JAK1 or JAK2, and the ability to overcome JAK
      inhibitor persistence are in various stages of development. First-in-class agents
      such as the activin receptor IIA ligand trap sotatercept (for anemia of MF), the
      telomerase inhibitor imetelstat, and the antifibrotic agent PRM-151 (recombinant
      human pentraxin-2) are also in clinical trials. In polycythemia vera, a novel
      interferon administered every 2 weeks is being developed for front-line therapy
      in high-risk individuals, and inhibitors of human double minute 2 (HDM2) have
      shown promise in preclinical studies, as have HDAC inhibitors such as givinostat
      (both in the laboratory and in the clinic). Ruxolitinib is approved for second
      line therapy of polycythemia vera and is being developed for essential
      thrombocythemia.

PMID- 28760305
TI  - Treatment Choices: A Quality of Life Comparison in Acute Myeloid Leukemia and
      High-risk Myelodysplastic Syndrome.
AB  - BACKGROUND: In the present exploratory, observational study, we compared the
      effect of intensive versus nonintensive treatment on quality of life for patients
      aged >= 60 years diagnosed with acute myeloid leukemia or high-risk
      myelodysplastic syndrome at 1 month after treatment. PATIENTS AND METHODS: A
      total of 73 patients with acute myeloid leukemia or high-risk myelodysplastic
      syndrome who had been treated at the inpatient and outpatient malignant
      hematology at Moffitt Cancer Center, a National Cancer Institute-designated
      comprehensive cancer center, were included. Two paired measurements of self
      reported quality of life were used, 1 before treatment and 1 at 1 month after
      treatment to compare intensive versus nonintensive treatment. Patients completed
      the Functional Assessment of Cancer Therapy-Leukemia version for the quality-of
      life measurement. Repeated measures analysis of variance was used to compare the
      effect of treatment and time and the interaction of treatment and time. The main
      research variables were intensive versus nonintensive treatment as the
      independent variable and quality of life measured using the Functional Assessment
      of Cancer Therapy-Leukemia version as the dependent variable. RESULTS: Physical
      function and leukemia symptoms improved for patients treated with intensive
      chemotherapy. A trend was found for improved quality of life for the intensive
      treatment compared with nonintensive treatment, for which the quality of life was
      stable at 1 month. CONCLUSION: The study participants treated with inpatient,
      induction chemotherapy experienced statistically significant improvement in their
      quality of life at 1 month. The outpatient, nonintensive study participants had
      stable quality of life at 1 month.

PMID- 28760306
TI  - High-risk Multiple Myeloma: Definition and Management.
AB  - The prognosis of patients with multiple myeloma has significantly improved after
      the introduction of novel concepts of immunomodulation and proteasome inhibition
      in myeloma therapies. In conjunction with the use of high-dose therapy and
      autologous stem cell transplantation, these newer antimyeloma agents facilitated
      the augmentation of deeper responses and as a result, enhanced survival outcomes.
      Despite mounting clinical evidence that novel therapies may mitigate the poor
      prognostic impact of some predictors historically considered "harbingers of doom"
      in myeloma such as t(4;14), the benefit of these advances is less evident in
      patients who present with genetically defined high-risk features such as presence
      of chromosomal abnormalities del17p, t(14;16), or t(14;20), or among patients
      presenting with plasma cell leukemia. With better understanding of the biology of
      the disease and further recognition of the genomic instability of the high-risk
      clonal plasma cell influencing both inherent and acquired therapeutic resistance,
      newer targeted treatment strategies will hopefully improve prognosis in future
      among this subset of patients with poorer outcomes. In this review, we not only
      focus on how to identify the genetically defined high-risk patients with myeloma
      but also describe the most optimal antimyeloma combination strategies that so far
      have shown to demonstrate long-term benefits for these patients.

PMID- 28760307
TI  - Survival Pattern of Hodgkin Lymphoma Patients in the Last 25 Years in Lebanon.
AB  - CONTEXT: After the emergence of combination chemotherapy in 1960s, survival of
      patients with Hodgkin lymphoma (HL) has dramatically improved worldwide. We lack
      studies that document the favorable evolution of survival regarding this disease
      in Lebanon. OBJECTIVE: To compare the overall survival in HL over 3 different
      decades in Lebanon. METHODS: We retrospectively reviewed the charts of 196
      patients diagnosed with HL, treated and followed from 1990 to 2015 in our center.
      Patients were divided into 3 groups according to period of analysis: group A
      (1990-1999), group B (2000-2009), and group C (2010-2015). We studied the
      characteristics and survival patterns of patients in each group. RESULTS: The
      male-to-female sex ratio was 1.06. The median age at diagnosis was 33 years in
      group A, 30.4 in group B, and 33.12 in group C (P = .6). Results showed
      variations in the subtypes of the disease according to the following: nodular
      sclerosis HL 59.5% in group A, 76.2% in group B, and 85.4% in group C. Mixed
      cellularity HL 21.6% in group A, 2.4% in group B, and 73.7% in group C (P =
      .0001). Patients presented with localized disease in 58.6%, 73.7%, and 56.4% in
      groups A, B, and C, respectively (P = .173). Complete remission was achieved in
      76.5% in group A, 85.3% in group B, and 69.5% in group C (P = .007). The survival
      rate at 5 years in group A was 91%, 94% in group B, and 100% in group C.
      CONCLUSION: The survival of patients with HL has dramatically improved over the
      past 25 years in Lebanon. These results resemble those achieved in Western
      countries due to the fast adoption of new molecular imaging technologies at
      diagnosis and follow-up and the rapid approval of new drugs for relapse in the
      Lebanese market.

PMID- 28760308
TI  - Real-life Experience for Integration of PET-CT in the Treatment of Hodgkin
      Lymphoma in Lebanon.
AB  - BACKGROUND: Hodgkin lymphoma (HL) is a highly curable disease; < 80% of patients
      will achieve long-term survival. Positron emission tomography-computed tomography
      (PET-CT) has played a major role in the evaluation of both disease staging and
      response and has become an essential component in tailoring patients' treatment.
      We report the effect of integrating PET-CT into the management of HL in Lebanon.
      PATIENTS AND METHODS: We analyzed the data regarding the usage of PET-CT at
      diagnosis, during treatment (interim PET), and at the end of treatment. We also
      analyzed the PET-CT findings from 2009 to 2015. RESULTS: The first PET-CT system
      was introduced in Lebanon in April 2002 but was not used for the evaluation of
      HL. Early in 2009, we started to incorporate PET-CT into the treatment of HL. By
      the end of 2009, 70% of patients were undergoing PET-CT at diagnosis and at the
      end of treatment. This proportion remained constant until 2013, when an increase
      occurred, with <= 94% of patients undergoing PET-CT at diagnosis. The usage of CT
      at diagnosis decreased significantly from 70% before 2009 to 52% after 2015. In
      contrast, CT usage at the end of treatment has fluctuated from 10% in 2009 to 0%
      in 2012, 2013, and 2014 and 11.76% in 2015. CONCLUSION: Functional imaging
      techniques are increasing in popularity compared with anatomic imaging. The usage
      of PET-CT has emerged as a highly valuable staging and follow-up method in the
      treatment of HL 8 years after the introduction of PET in Lebanon. PET was used
      first to improve the staging, then to evaluate the treatment response, and,
      recently, to tailor therapy according to the response.

PMID- 28760309
TI  - Autologous Stem Cell Transplant: Still the Standard for Fit Patients With Mantle
      Cell Lymphoma.
AB  - Mantle cell lymphoma is a relatively rare malignancy, comprising fewer than 10%
      of all non-Hodgkin lymphomas. It is a heterogeneous disease, and although most
      patients experience an aggressive clinical course, some have a more indolent
      disease and may not require immediate therapy. There are currently few reliable
      prognostic markers, making it difficult to accurately predict which patients
      require early intensive treatment. We argue that consolidative autologous stem
      cell transplantation in first remission remains the standard of care for the
      young and fit patient population, based on long-term data from phase II and III
      trials demonstrating that early transplantation extends both progression-free and
      overall survival. Novel targeted agents are currently being investigated in both
      the upfront and relapse settings, but to date there are few data to suggest
      durable treatment responses that compare favorably with results of
      transplantation.

PMID- 28760310
TI  - Ocular Complications in Survivors of the Ebola Outbreak in Guinea.

PMID- 28760311
TI  - [Targeted pharmacist-led medication order review in hospital: Assessment of a
      selection method for drug prescriptions].
AB  - OBJECTIVES: The aim of this study was to assess a selection method for drug
      prescriptions developed at the hospital level that allows to target pharmacist
      led medication order review for at-risk patients and drugs. METHODS: A one-month
      study has been conducted on all targeted medication orders in 19 care units.
      Selection criteria have been identified: biological criteria, alert medications
      and drug interactions. Pharmacists' interventions proposed during medication
      order review were listed and the possible links to the selection criteria were
      determined. RESULTS: A total of 1612 prescriptions were analysed and 236
      pharmacists' interventions were performed (14.6 interventions per 100
      prescriptions). Physicians' acceptance rate was 60.6%. The percentage of
      pharmacists' interventions linked to the selection criteria was 35.6%. The
      relevance of the biological criteria was identified, particularly the one
      identifying patients with creatinine clearance below 30ml/min. Six alert
      medications were also relevant selection criteria: dabigatran, morphine,
      gentamicin, methotrexate, potassium chloride and trimethoprim sulfamethoxazole.
      Drug interactions criteria was irrelevant. CONCLUSIONS: This study allowed a
      first assessment of the selection criteria used. A largest study seems necessary
      to continue the analysis of this selection method for prescriptions, especially
      the assessment of the alert medications list, in order to refine the
      prescriptions targeting.

PMID- 28760312
TI  - [Tyrosine kinase inhibitor as adjuvant treatment of renal cell carcinoma: 1
      versus 3].

PMID- 28760313
TI  - Recent advances (2015-2016) in anticancer hybrids.
AB  - In spite of the development of a large number of novel anticancer drugs over the
      years, Cancer remains as a prominent cause of death, worldwide. Numerous drugs
      that are currently in clinical practice have developed multidrug resistance along
      with fatal side effects. Therefore, the utilization of single-target therapy is
      incapable of providing an effective control on the malignant process. Molecular
      hybridization, involving a combination of two or more pharmacophores of bioactive
      scaffolds to generate a single molecular architecture with improved affinity and
      activity, in comparison to their parent molecules, has emerged as a promising
      strategy in recent drug discovery research. Hybrid anticancer drugs are of great
      therapeutic interests since they can potentially overcome most of the
      pharmacokinetic drawbacks encountered with conventional anticancer drugs.
      Strategically, the design of anticancer drugs involved the blending or linking of
      an anticancer drug with another anticancer drug or a carrier molecule which can
      efficiently target cancer cells with improved biological potential. Major
      advantages of hybrid anticancer drugs involved increased specificity, better
      patient compliance, and lower side effects along with reduction in chemo
      resistance. The successful utilization of this technique in design and synthesis
      of novel anticancer hybrids has been well illustrated and documented in the
      literature. The purpose of the present review article will be to provide an
      emphasis on the recent developments (2015-16) in anticancer hybrids with insights
      into their structure-activity relationship (SAR) and mechanism of action.

PMID- 28760314
TI  - Medication-related osteonecrosis of the jaw in oncological patients with skeletal
      metastases: conservative treatment is effective up to stage 2.
AB  - There is currently no widespread strategy for treating medication-related
      osteonecrosis of the jaw (MRONJ), so our aim was to evaluate retrospectively the
      outcome of a minimally invasive treatment protocol for patients with both MRONJ
      and cancer. We designed a retrospective cohort study of patients with cancer who
      had been diagnosed with MRONJ after treatment with denosumab or bisphosphonates
      given intravenously. Primary outcome measures were improvement in the clinical
      stage of MRONJ and the time course to its resolution. Secondary outcome measures
      included the incidence of risk factors and patterns of treatment. Seventy-nine
      patients with 109 lesions were enrolled, and their characteristics, presentation
      of the lesions, complications, and relations to previous oral interventions were
      recorded. Treatment depended on the stage of disease, and included conservative
      medical, and minimally-invasive surgical, procedures. There was complete healing
      and resolution of disease in 38/57 stage 1 lesions, 30/47 stage 2 lesions, and
      3/5 stage 3 lesions. The symptoms improved in 16/47 stage 2 lesions, and 2/5
      stage 3 lesions. Fifteen of the stage 1 lesions, and one of the stage 2 lesions,
      failed to respond. Despite the possibility of an aggressive approach to the
      treatment of MRONJ, conservative treatment remains the first line of defence as
      regression is obvious, with evidence of no evolution to a higher stage. In our
      experience surgical intervention is recommended in persistent stage 3 MRONJ that
      has failed to respond to conservative treatment.

PMID- 28760315
TI  - Parental Opioid Abuse: Barriers to Care, Policy, and Implications for Primary
      Care Pediatric Providers.
AB  - Parental opioid use is affecting the physical, developmental, and mental health
      of the pediatric population nationwide and raises questions of safety when these
      children remain in the care of opioid-addicted parents. Pediatric providers face
      many barriers to identifying and caring for children beyond the neonatal period
      who have been affected by parental opioid abuse both in utero and in the home.
      These barriers include communication between providers and services,
      identification of intrauterine exposure, parental opioid abuse screening, and
      knowledge of child protective services involvement. In addition, understanding
      current state and national health policy regarding parental opioid abuse helps
      providers navigate these barriers. The purpose of this article is to identify
      barriers to care of children affected by parental opioid abuse both in utero and
      in the home, to discuss current health policy surrounding the issue, and to
      identify implications for the care of these children in the primary care
      pediatric setting.

PMID- 28760316
TI  - Developing a Transition Care Coordination Program for Youth With Spina Bifida.
AB  - INTRODUCTION: This quality improvement pilot study focused on developing and
      facilitating readiness for transition in youth with spina bifida. The results
      contribute to a broader institution-wide initiative at a subspecialty pediatric
      organization. METHODS: The clinical roles of six nurse care coordinators were
      restructured to add responsibility for transition care coordination. Together,
      parents, youth, and nurse transition care coordinators created and implemented
      individualized family-centered care plans focused on improving self-management
      and readiness for transition to adulthood. The Transition Readiness Assessment
      Questionnaire was administered before and after intervention initiation. RESULTS:
      Fourteen youth-parent pairs participated in this study. Postintervention
      Transition Readiness Assessment Questionnaire results indicated that both parents
      and youth perceived improvement in transition readiness. Youth perceived more
      improvement than did parents. DISCUSSION: This pilot study showed that budget
      neutral processes can be systematically implemented to facilitate transition
      preparation from pediatric to adult health care services for youth with spina
      bifida and their families.

PMID- 28760317
TI  - Evaluating the Use of a Stability Guideline for Long-Term Ventilator-Dependent
      Children Discharging to Home: A Quality Improvement Project.
AB  - INTRODUCTION: Defining stability before discharge for children with severe
      chronic lung disease requiring home ventilation has historically been dependent
      on an individual provider's opinion. METHODS: An institutional guideline based on
      expert opinion was used for patients who were first discharged home on mechanical
      ventilation. A retrospective review determined if the guideline was used.
      Electronic medical record changes were initiated to improve compliance with the
      guideline. RESULTS: The retrospective review showed that the guideline is
      documented in less than one third of patients, and 36% of patients met the
      requirements of the guideline before discharge. Following these results,
      electronic medical record documentation was changed. DISCUSSION: Results showed a
      low utilization rate for the discharge home guideline for patients receiving long
      term ventilation. Utilization of electronic medical record charting can improve
      the tracking of stability guidelines and provide the opportunity to further
      define stability in ventilator-dependent children.

PMID- 28760318
TI  - The horizontal inclination angle is associated with the risk of inferior alveolar
      nerve injury during the extraction of mandibular third molars.
AB  - The extraction of mandibular third molars can lead to injury to the inferior
      alveolar nerve. Hence, it is important to assess the proximity of the root to the
      inferior alveolar canal before extraction. The classification system of Pell and
      Gregory and the Winter classification are commonly used to evaluate the
      positional relationship of the third molar based on radiographs. This
      retrospective study involving 105 mandibular third molars was performed to assess
      whether these systems reflect the proximity of the root to the canal (based on
      computed tomography images), and to identify risk factors for nerve injury.
      Regarding the prediction of computed tomography-verified canal invasion, the
      sensitivity, specificity, and positive and negative predictive values were high
      for each Pell and Gregory category when there was radiographic evidence. The mean
      distance of invasion was significantly greater in class III than in class I.
      However, there were no significant differences between the Winter inclination
      categories. The mean distance differed significantly between a horizontal
      inclination angle to the buccal side of >5 degrees  and an angle of <=5 degrees .
      Thus, a horizontal inclination angle >5 degrees  represents a novel risk factor
      for nerve injury.

PMID- 28760319
TI  - Maxillomandibular advancement as the initial treatment of obstructive sleep
      apnoea: Is the mandibular occlusal plane the key?
AB  - Maxillomandibular advancement (MMA) can be effective for managing obstructive
      sleep apnoea (OSA); however, limited information is available on the predictor
      surgical variables. This study investigated whether normalization of the
      mandibular occlusal plane (MOP) was a determinant factor in curing OSA. Patients
      with moderate or severe OSA who underwent MMA were evaluated by preoperative and
      postoperative three-dimensional (3D) scans and polysomnograms. The postoperative
      value of MOP and the magnitude of skeletal advancement were the predictor
      variables; change in the apnoea-hypopnoea index (AHI) was the main outcome
      variable. Thirty-four subjects with a mean age of 41+/-14years and 58,8% female
      were analysed. The Epworth Sleepiness Scale (ESS) was 17.4+/-5.4 and AHI was
      38.3+/-10.7 per hour before surgery. Postoperative AHI was 6.5+/-4.3 per hour
      (P<0.001) with 52.94% of the patients considered as cured, and 47.06% suffering
      from a mild residual OSA with ESS 0.8+/-1.4 (P<0.001). 3D changes revealed a
      volume increase of 106.3+/-38.8%. The mandible was advanced 10.4+/-3.9mm and
      maxilla 4.9+/-3.2mm. MOP postoperative value was concluded to be the best
      predictor variable. Treatment planning should include MOP normalization and a
      mandibular advancement between 6 and 10mm. The maxillary advancement would depend
      on the desired aesthetic changes and final occlusion.

PMID- 28760320
TI  - The Microbiology of Ruthenium Complexes.
AB  - Ruthenium is seldom mentioned in microbiology texts, due to the fact that this
      metal has no known, essential roles in biological systems, nor is it generally
      considered toxic. Since the fortuitous discovery of cisplatin, first as an
      antimicrobial agent and then later employed widely as an anticancer agent,
      complexes of other platinum group metals, such as ruthenium, have attracted
      interest for their medicinal properties. Here, we review at length how ruthenium
      complexes have been investigated as potential antimicrobial, antiparasitic and
      chemotherapeutic agents, in addition to their long and well-established roles as
      biological stains and inhibitors of calcium channels. Ruthenium complexes are
      also employed in a surprising number of biotechnological roles. It is in the
      employment of ruthenium complexes as antimicrobial agents and alternatives or
      adjuvants to more traditional antibiotics, that we expect to see the most
      striking developments in the future. Such novel contributions from organometallic
      chemistry are undoubtedly sorely needed to address the antimicrobial resistance
      crisis and the slow appearance on the market of new antibiotics.

PMID- 28760321
TI  - Mechanism and Role of Globin-Coupled Sensor Signalling.
AB  - The discovery of the globin-coupled sensor (GCS) family of haem proteins has
      provided new insights into signalling proteins and pathways by which organisms
      sense and respond to changing oxygen levels. GCS proteins consist of a sensor
      globin domain linked to a variety of output domains, suggesting roles in
      controlling numerous cellular pathways, and behaviours in response to changing
      oxygen concentration. Members of this family of proteins have been identified in
      the genomes of numerous organisms and characterization of GCS with output
      domains, including methyl accepting chemotaxis proteins, kinases, and diguanylate
      cyclases, have yielded an understanding of the mechanism by which oxygen controls
      activity of GCS protein output domains, as well as downstream proteins and
      pathways regulated by GCS signalling. Future studies will expand our
      understanding of these proteins both in vitro and in vivo, likely demonstrating
      broad roles for GCS in controlling oxygen-dependent microbial physiology and
      phenotypes.

PMID- 28760322
TI  - Cytochrome bd and Gaseous Ligands in Bacterial Physiology.
AB  - Cytochrome bd is a unique prokaryotic respiratory terminal oxidase that does not
      belong to the extensively investigated family of haem-copper oxidases (HCOs). The
      enzyme catalyses the four-electron reduction of O2 to 2H2O, using quinols as
      physiological reducing substrates. The reaction is electrogenic and cytochrome bd
      therefore sustains bacterial energy metabolism by contributing to maintain the
      transmembrane proton motive force required for ATP synthesis. As compared to
      HCOs, cytochrome bd displays several distinctive features in terms of (i) metal
      composition (it lacks Cu and harbours a d-type haem in addition to two haems b),
      (ii) overall three-dimensional structure, that only recently has been solved, and
      arrangement of the redox cofactors, (iii) lesser energetic efficiency (it is not
      a proton pump), (iv) higher O2 affinity, (v) higher resistance to inhibitors such
      as cyanide, nitric oxide (NO) and hydrogen sulphide (H2S) and (vi) ability to
      efficiently metabolize potentially toxic reactive oxygen and nitrogen species
      like hydrogen peroxide (H2O2) and peroxynitrite (ONOO-). Compelling evidence
      suggests that, beyond its bioenergetic role, cytochrome bd plays multiple
      functions in bacterial physiology and affords protection against oxidative and
      nitrosative stress. Relevant to human pathophysiology, thanks to its peculiar
      properties, the enzyme has been shown to promote virulence in several bacterial
      pathogens, being currently recognized as a target for the development of new
      antibiotics. This review aims to give an update on our current understanding of
      bd-type oxidases with a focus on their reactivity with gaseous ligands and its
      potential impact on bacterial physiology and human pathophysiology.

PMID- 28760323
TI  - Haem-Based Sensors of O2: Lessons and Perspectives.
AB  - Haem-based sensors have emerged during the last 15 years as being a large family
      of proteins that occur in all kingdoms of life. These sensors are responsible
      mainly for detecting binding of O2, CO and NO and reporting the ligation status
      to an output domain with an enzymatic or macromolecule-binding property. A myriad
      of biological functions have been associated with these sensors, which are
      involved in vasodilation, bacterial symbiosis, chemotaxis and biofilm formation,
      among others. Here, we critically review several bacterial systems for O2 sensing
      that are extensively studied in many respects, focusing on the lessons that are
      important to advance the field.

PMID- 28760324
TI  - The Role of Plant Growth-Promoting Bacteria in Metal Phytoremediation.
AB  - Phytoremediation is a promising technology that uses plants and their associated
      microbes to clean up contaminants from the environment. In recent years,
      phytoremediation assisted by plant growth-promoting bacteria (PGPB) has been
      highly touted for cleaning up toxic metals from soil. PGPB include rhizospheric
      bacteria, endophytic bacteria and the bacteria that facilitate phytoremediation
      by other means. This review provides information about the traits and mechanisms
      possessed by PGPB that improve plant metal tolerance and growth, and illustrate
      mechanisms responsible for plant metal accumulation/translocation in plants.
      Several recent examples of phytoremediation of metals facilitated by PGPB are
      reviewed. Although many encouraging results have been reported in the past years,
      there have also been numerous challenges encountered in phytoremediation in the
      field. To implement PGPB-assisted phytoremediation of metals in the natural
      environment, there is also a need to critically assess the ecological effects of
      PGPB, especially for those nonnative bacteria.

PMID- 28760325
TI  - Commentary on "A Pilot Study of Femoropopliteal Artery Revascularisation With a
      Low dose Paclitaxel Coated Balloon: Is Predilatation Necessary?"

PMID- 28760326
TI  - Subcutaneuos emphisema after endoscopic retrograde cholangio-pancreatography.

PMID- 28760327
TI  - Comment on: mid-term effects bariatric surgery in subjects with insulin-treated
      type 2 diabetes.

PMID- 28760328
TI  - Psychosocial characteristics associated with symptom perception 1 year after
      gastric bypass surgery-a prospective study.
AB  - BACKGROUND: The experience of symptoms after bariatric surgery, such as pain,
      dumping, and fatigue, may affect behavior, quality of life, and the need for
      healthcare consultations. Attention to and interpretation of symptoms are
      influenced by psychological and contextual factors. Prospective studies of
      psychological factors predicting physical symptom perception after bariatric
      surgery are scarce. OBJECTIVES: To explore associations of preoperative negative
      affect and history of stressful and traumatic events with frequency and intensity
      of self-reported symptoms 1 year after Roux-en-Y gastric bypass (RYGB). SETTING:
      University hospital. METHODS: Questionnaire data were collected before and 1 year
      after RYGB from 230 patients. Negative affect and stressful events were measured
      preoperatively. The participants reported the number and impact of various
      physical symptoms postoperatively. RESULTS: The most common symptoms reported to
      have a high impact on behavior were fatigue (32.8%) and dumping (28.4%).
      Reporting more symptoms was associated with preoperative anxiety (r = .22, P =
      .001) and the number of stressful life events (r = .21, P = .002). Participants
      with a probable preoperative anxiety disorder reported a higher impact of
      fatigue, pain, dumping, and diarrhea after surgery, while those with a probable
      mood disorder and a history of traumatic sexual/violent events reported a higher
      impact of dumping. CONCLUSION: Preoperative anxiety symptoms and stressful
      experiences were associated with a higher perceived impact of symptoms, such as
      dumping, fatigue, and pain after RYGB. The evaluation of psychological
      characteristics associated with symptom perception may be relevant when managing
      symptoms that are not responsive to other treatment measures.

PMID- 28760329
TI  - Micro-elimination - A path to global elimination of hepatitis C.

PMID- 28760330
TI  - Thermographic analysis of the effect of composite type, layering method, and
      curing light on the temperature rise of photo-cured composites in tooth cavities.
AB  - OBJECTIVES: The purpose of this study was to investigate temperature rise in the
      composite and dentin of a class I cavity in extracted human molars under
      different restoration conditions, including the use of different composite types,
      layering methods, and curing lights. METHODS: Open occlusal cavities were
      prepared on 28 extracted human molars. A conventional (Filtek Z250) and a bulk
      fill (Filtek Bulk Fill Posterior; BFP) composite were used to restore the
      preparations. BFP was incrementally layered or bulk-filled. Bulk-filled BFP was
      cured with two different lights, the Elipar S10 and the BeLite. Each layer was
      illuminated for 20s, while thermograms of the specimens were recorded for 100s
      using an infrared thermal camera. Temperature changes on the composite and dentin
      surfaces were obtained at points of interest (POI) pertaining to successive
      incremental distances of 0.75mm from the top of the cavity to the pulp. The
      polymerization kinetics of each composite was determined using photo-differential
      scanning calorimetry. RESULTS: The greatest temperature rise was observed 0.75mm
      apical from the top of the cavity. All groups showed over 6 degrees C maximum
      temperature rise (DeltaTmax) at the pulpal side of the dentin. Upon curing, Z250
      reached DeltaT=5 degrees C faster than BFP; however, DeltaTmax of the two
      composites were comparable at any POI. Bulk filling showed greater DeltaTmax than
      incremental filling at 0.75mm apical from the top and in the middle of the
      cavity. The Elipar S10 light generated faster temperature changes in the curing
      composite at all recorded positions throughout the depth of the cavity and
      greater DeltaTmax in all POIs compared to BeLite. SIGNIFICANCE: Real-time
      thermographic analysis demonstrated that the composite type and layering method
      did not influence the temperature rise at the pulpal side of dentin during
      composite restoration of an occlusal preparation in a tooth. The amount and
      initial rate of temperature increase was most affected by the radiant exposure of
      the light curing unit. Within the limitations of this in vitro study, when
      irradiation time is constant, a curing light with higher radiant power can induce
      relatively high thermal transfer, thereby increasing the risk of pulpal damage.

PMID- 28760331
TI  - The applicability of new TNM classification for humanpapilloma virus-related
      oropharyngeal cancer in the 8th edition of the AJCC/UICC TNM staging system in
      Japan: A single-centre study.
AB  - OBJECTIVE: The purpose of this study is to validate the applicability of new TNM
      classification for human papillomavirus (HPV)-related oropharyngeal cancer (OPC)
      in the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for
      International Cancer Control (UICC) TNM staging system in Japan. METHODS: A total
      of 91 OPC patients treated with radiation-based therapy between November 2001 and
      July 2015 were analyzed retrospectively in this study. HPV infection status was
      evaluated using tumor p16 expression. RESULTS: 40 OPC patients (44.0%) had HPV
      positive disease in this study. The distribution of disease stage of HPV-positive
      OPC patients dramatically changed from the 7th edition to the 8th edition of
      AJCC/UICC TNM classification. However, neither the 8th edition nor the 7th
      edition of the AJCC/UICC TNM staging system could adequately predict outcomes of
      HPV-positive OPC patients in our patient series. On the other hand, our
      multivariate analysis indicated that matted nodes and age >=63 were independent
      prognostic factors for progression-free survival. In addition, HPV-positive OPC
      patients with stage I without matted nodes showed significantly better overall
      and progression-free survival compared with those with stage I with matted nodes
      and stages II and III in the 8th edition of the AJCC/UICC TNM staging system
      (P=0.008, and P=0.043, respectively). CONCLUSION: Our results suggested that
      matted nodes of HPV-positive OPC patients might be additionally examined to apply
      the 8th edition of AJCC/UICC TNM classification for more adequate predicting
      outcomes of HPV-positive OPC patients.

PMID- 28760332
TI  - Evidence of surgical treatments for intractable Meniere's disease.
AB  - Meniere's disease is an inner ear disease, characterized by recurrent rotatory
      vertigo, sensorineural hearing loss and tinnitus. There are some with frequent
      vertigo attacks, progressive hearing loss and persistent annoying tinnitus even
      through the continuous standard medical treatments. These cases are thought to
      account for 10%-20% of all cases of Meniere's disease. In this review article, we
      would like to demonstrate the evidences for surgical treatments according to the
      previous papers, and consider the next therapeutic strategies including surgical
      options according to the international guidelines.

PMID- 28760334
TI  - Erratum Regarding "AJKD Atlas of Renal Pathology: Kidney Disease in Primary
      Sjogren Syndrome" (Am J Kidney Dis. 2017;69[6]:e29-e30).

PMID- 28760333
TI  - "We black women have to kill a lion everyday": An intersectional analysis of
      racism and social determinants of health in Brazil.
AB  - The concept of intersectionality has been used to analyze and understand how
      multiple forms of identity and oppression interact to shape life experiences of
      marginalized groups. We conducted a qualitative study to explore how Black
      Brazilian women experience the intersections of race, class, and gender and the
      ways in which these intersecting experiences act as social determinants of
      health. Nine focus groups were conducted with Black, White, and mixed-race women
      of childbearing age (n = 37), social and health activists (n = 11), and health
      professionals (n = 20). The focus groups took place in two cities in the
      Brazilian state of Bahia during October and November 2012. Using a comparative
      approach, we describe participants' responses regarding the life experiences of
      women of differing racial and class backgrounds. Our findings highlight how the
      intersectional relationship between race, class, and gender alters women's social
      context and life course opportunities, as well as their stressors and protective
      buffers. We argue that the differing intersectional experiences of women due to
      race and class create unique social contexts that define the parameters of health
      and wellness. In addition, we argue that the experiences at each intersection
      (i.e., raceXclass, raceXgender, classXgender, raceXclassXgender) have a unique
      character that can be qualitatively described. Improved specification of
      exposures experienced by marginalized populations who experience intersecting
      forms of oppression can help explain intra- and inter-group differences in health
      outcomes, and may also lead to improved intervention models.

PMID- 28760335
TI  - MicroRNA-21 regulates peroxisome proliferator-activated receptor alpha, a
      molecular mechanism of cardiac pathology in Cardiorenal Syndrome Type 4.
AB  - Cardiovascular events are the leading cause of death in patients with chronic
      kidney disease (CKD), although the pathological mechanisms are poorly understood.
      Here we longitudinally characterized left ventricle pathology in a 5/6
      nephrectomy rat model of CKD and identify novel molecular mediators. Next
      generation sequencing of left ventricle mRNA and microRNA (miRNA) was performed
      at physiologically distinct points in disease progression, identifying
      alterations in genes in numerous immune, lipid metabolism, and inflammatory
      pathways, as well as several miRNAs. MiRNA miR-21-5p was increased in our dataset
      and has been reported to regulate many identified pathways. Suppression of miR-21
      5p protected rats with 5/6 nephrectomy from developing left ventricle hypertrophy
      and improved left ventricle function. Next-generation mRNA sequencing revealed
      that miR-21-5p suppression altered gene expression in peroxisome proliferator
      activated receptor alpha (PPARalpha) regulated pathways in the left ventricle.
      PPARalpha, a miR-21-5p target, is the primary PPAR isoform in the heart,
      importantly involved in regulating fatty acid metabolism. Therapeutic delivery of
      low-dose PPARalpha agonist (clofibrate) to rats with 5/6 nephrectomy improved
      cardiac function and prevented left ventricle dilation. Thus, comprehensive
      characterization of left ventricle molecular changes highlights the involvement
      of numerous signaling pathways not previously explored in CKD models and
      identified PPARalpha as a potential therapeutic target for CKD-related cardiac
      dysfunction.

PMID- 28760336
TI  - Dietary magnesium supplementation prevents and reverses vascular and soft tissue
      calcifications in uremic rats.
AB  - Although magnesium has been shown to prevent vascular calcification in vitro,
      controlled in vivo studies in uremic animal models are limited. To determine
      whether dietary magnesium supplementation protects against the development of
      vascular calcification, 5/6 nephrectomized Wistar rats were fed diets with
      different magnesium content increasing from 0.1 to 1.1%. In one study we analyzed
      bone specimens from rats fed 0.1%, 0.3%, and 0.6% magnesium diets, and in another
      study we evaluated the effect of intraperitoneal magnesium on vascular
      calcification in 5/6 nephrectomized rats. The effects of magnesium on established
      vascular calcification were also evaluated in uremic rats fed on diets with
      either normal (0.1%) or moderately increased magnesium (0.6%) content. The
      increase in dietary magnesium resulted in a marked reduction in vascular
      calcification, together with improved mineral metabolism and renal function.
      Moderately elevated dietary magnesium (0.3%), but not high dietary magnesium
      (0.6%), improved bone homeostasis as compared to basal dietary magnesium (0.1%).
      Results of our study also suggested that the protective effect of magnesium on
      vascular calcification was not limited to its action as an intestinal phosphate
      binder since magnesium administered intraperitoneally also decreased vascular
      calcification. Oral magnesium supplementation also reduced blood pressure in
      uremic rats, and in vitro medium magnesium decreased BMP-2 and p65-NF-kappaB in
      TNF-alpha-treated human umbilical vein endothelial cells. Finally, in uremic rats
      with established vascular calcification, increasing dietary magnesium from 0.1%
      magnesium to 0.6% reduced the mortality rate from 52% to 28%, which was
      associated with reduced vascular calcification. Thus, increasing dietary
      magnesium reduced both vascular calcification and mortality in uremic rats.

PMID- 28760337
TI  - Somatic mosaicism represents an underestimated event underlying collagen 6
      related disorders.
AB  - BACKGROUND: Collagen VI-related disorders (COL6-RD) are a group of heterogenous
      muscular diseases due to mutations in the COL6A1, COL6A2 and COL6A3 genes,
      encoding for collagen VI, a critical component of the extracellular matrix.
      Ullrich congenital muscle disorder and Bethlem myopathy represent the ends of a
      clinical spectrum that includes intermediate phenotypes of variable severity.
      UCMD are caused by recessive loss of function mutations or de-novo dominant
      negative mutations. The intermediate phenotype and BM are more commonly caused by
      dominantly acting mutations, and less commonly by recessive mutations. Recently
      parental mosaicism for dominant mutations in COL6 have been reported in four COL6
      RD families and germinal mosaicism has been also identified in a family with
      recurrence of UCMD in two half-sibs. METHODS AND RESULTS: Here we report three
      unrelated patients affected by a COL6-RD who carried de novo mosaic mutations in
      COL6A genes. These mutations, missed by Sanger sequencing, were identified by
      next generation sequencing. CONCLUSIONS: This report highlights the importance of
      a complete diagnostic workup when clinical and histological finding are
      consistent with a COL6-RD and strengthen the impression that mosaicisms are
      underestimated events underlying COL6-RD.

PMID- 28760338
TI  - Structural dynamics of Gialpha protein revealed by single molecule FRET.
AB  - The heterotrimeric G proteins (Galphabetagamma) act as molecular switches to
      mediate signal transduction from G protein-coupled receptors to downstream
      effectors. Upon interaction with an activated receptor, G protein exchanges its
      bound GDP with GTP, stimulating downstream signal transmission. Release of GDP
      requires a structural rearrangement between the GTPase domain and helical domain
      of the Galpha subunit. Here, we used single molecule fluorescence resonance
      energy transfer (smFRET) technique to study the conformational dynamics of these
      two domains in the apo state and in the binding of different ligands. Direct
      imaging of individual molecules showed that the Gialpha subunit is highly
      dynamic, and at least three major conformations of Gialpha could be observed in
      the apo state. Upon binding of GDP, Gialpha becomes dramatically less dynamic,
      resulting in a closed conformation between the two domains. We postulate that
      changes between the three conformations are sequential, and the three
      conformations appear to have distinct affinities toward GDP.

PMID- 28760339
TI  - Crystal structure of importin-alpha3 bound to the nuclear localization signal of
      Ran-binding protein 3.
AB  - Ran-binding protein 3 (RanBP3) is a primarily nuclear Ran-binding protein that
      functions as an accessory factor in the Ran GTPase system. RanBP3 associates with
      Ran-specific nucleotide exchange factor RCC1 and enhances its catalytic activity
      towards Ran. RanBP3 also promotes CRM1-mediated nuclear export as well as CRM1
      independent nuclear export of beta-catenin, Smad2, and Smad3. Nuclear import of
      RanBP3 is dependent on the nuclear import adaptor protein importin-alpha and,
      RanBP3 is imported more efficiently by importin-alpha3 than by other members of
      the importin-alpha family. Protein kinase signaling pathways control
      nucleocytoplasmic transport through phosphorylation of RanBP3 at Ser58,
      immediately C-terminal to the nuclear localization signal (NLS) in the N-terminal
      region of RanBP3. Here we report the crystal structure of human importin-alpha3
      bound to an N-terminal fragment of human RanBP3 containing the NLS sequence that
      is necessary and sufficient for nuclear import. The structure reveals that RanBP3
      binds to importin-alpha3 residues that are strictly conserved in all seven
      isoforms of human importin-alpha at the major NLS-binding site, indicating that
      the region of importin-alpha outside the NLS-binding site, possibly the
      autoinhibotory importin-beta1-binding domain, may be the key determinant for the
      preferential binding of RanBP3 to importin-alpha3. Computational docking
      simulation indicates that phosphorylation of RanBP3 at Ser58 could potentially
      stabilize the association of RanBP3 with importin-alpha through interactions
      between the phosphate moiety of phospho-Ser58 of RanBP3 and a cluster of basic
      residues (Arg96 and Lys97 in importin-alpha3) on armadillo repeat 1 of importin
      alpha.

PMID- 28760340
TI  - Synergistic effects of combination treatment using EGCG and suramin against the
      chikungunya virus.
AB  - Chikungunya is a severe disease that results from infection with the chikungunya
      virus (CHIKV), an arbovirus. Thus, we (1) explored a new approach to combining
      previously researched drugs that have shown the potential to inhibit CHIKV
      infection; and (2) demonstrated the antiviral effects of (-)-Epigallocatechin-3
      gallate (EGCG) and the underlying mechanisms. Specifically, we used U2OS cells
      infected with CHIVK to assess the synergistic antiviral activities of EGCG and
      suramin. EGCG presented the ability to inhibit the viral RNA, progeny yield, and
      cytopathic effect (CPE) of CHIKV and also demonstrated the ability to protect
      against virus entry, replication, and release. Moreover, the results confirmed
      that EGCG and suramin can have synergistic effects against CHIKV strain S27
      infection and two other clinical isolates of CHIKV. Our findings suggest that
      treatment with a combination of EGCG and suramin could provide a basis for the
      development of novel stretages against CHIKV infection.

PMID- 28760341
TI  - Biological effects of anti-RANKL antibody administration in pregnant mice and
      their newborns.
AB  - Denosumab, a fully human monoclonal antibody that neutralizes receptor activator
      of nuclear factor-kappaB ligand (RANKL) and blocks osteoclast differentiation,
      has received approval in Japan for use as an anti-resorptive drug for
      osteoporosis and skeletal-related events (SREs) in patients with solid cancer.
      Denosumab is contraindicated during pregnancy, though the effects of blocking
      RANKL activity on pregnant mothers and their newborns are unclear. We used mice
      to investigate the effects of an anti-RANKL antibody on maternal and newborn
      health. Mothers injected with the anti-RANKL antibody had increased bone mass as
      compared with the controls, while osteoclast number and the level of tartrate
      resistant acid phosphatase (TRAP) in serum were increased at the end of
      pregnancy. Newborn mice exposed to the antibody in utero were normally born, but
      showed increased bone mass and died within 48 h after birth. None of the newborns
      were found to have milk in their stomachs, suggesting that they died due to a
      maternal defect in lactation. Consistent with this, anti-RANKL antibody-injected
      mothers displayed impaired mammary gland development. However, fostering by
      healthy surrogate mothers rescued only 33% of the antibody-exposed newborns,
      suggesting that neonatal mortality was due, at least in part, to an intrinsic
      defect in the newborns. Our findings show that anti-RANKL antibody administration
      during pregnancy results in not only an undesirable increase in bone mass, but
      also has harmful effects on newborn survival.

PMID- 28760342
TI  - Induction of alpha6 and beta1 integrins by acupuncture stimulation in rats.
AB  - Acupuncture therapy is performed by applying the needle insertion at discrete
      cutaneous locations and used for the treatments of diverse symptoms and
      disorders. In order to elucidate mechanistic basis on how acupuncture stimulation
      (AS) produces therapeutic effects, it is primarily important to understand tissue
      responses locally at the acupuncture site (acupoint). Here, we investigated
      integrin protein as molecular target responding to and integrating AS. Signals of
      alpha6 and beta1 integrins were clearly induced at zusanli acupoint 24 h after AS
      in areas of nuclear clusters around the needle track. Induction levels of
      integrin were largely reduced by needle insertion at non-acupuncture point or
      without needle rotation. Phospho-Erk1/2 was initially decreased below the basal
      level after AS but increased 24 h later. Induction pattern of phospho-Erk1/2 was
      as similar as that of alpha6 integrin in its selectivity to needling procedure
      and tissue distribution. We further found that mRNA expression of P2X3 purinergic
      receptor was upregulated in the dorsal root ganglion (DRG) after AS, but
      decreased by the inhibition of Erk1/2 activity at the acupuncture area. Moreover,
      AS-mediated integrin activation was required for Erk1/2 activation at the
      acupuncture site and regulation of pain sensitivity in the hind paw. The present
      results provide a new evidence on acupuncture-specific tissue response in terms
      of integrin induction, and further suggest that integrin activation may be
      involved in transmitting mechanosensory signals from the acupoint to afferent
      nerve fiber.

PMID- 28760343
TI  - RACK1 promotes radiation resistance in esophageal cancer via regulating AKT
      pathway and Bcl-2 expression.
AB  - RACK1 is a seven Trp-Asp 40 repeat protein, which interacts with a wide range of
      kinases and proteins. RACK1 plays an important role in the proliferation and
      progression of various cancers. The aim of this study is to detect the role of
      RACK1 in the radioresistance in esophageal cancer. The results indicated that
      downregulation of RACK1 reduced the colony formation ability, proliferation
      ability and resistance of cells to radiation effection through regulating the
      radiation-related proteins including pAKT, Bcl-2 and Bim; whereas upregulation of
      RACK1 promoted the ability and radioresistance of ESCC cells. Our findings
      suggest that RACK1 promotes proliferation and radioresistance in ESCC cells by
      activating the AKT pathway, upregulating Bcl-2 expression and downregulating
      protein levels of Bim. Our study fills in gaps in the field of RACK1 and
      radiation resistance and may provide new possibilities for improving strategies
      of radiotherapy in esophageal cancer.

PMID- 28760344
TI  - [Adapting and validating the generic instrument CollaboRATETM to measure women's
      participation in health related decision-making during the reproductive process].
AB  - INTRODUCTION: There is a worldwide interest in involving patients in health
      related decisions, so patients can actively search for therapeutic options and
      choose course of action that allows them to have better quality of life and
      wellbeing. The majority of the instruments available to capture the degree of
      participation in medical decision-making are in English and have been developed
      in high income countries. OBJECTIVE: To adapt and validate for the Chilean
      context the instrument CollaboRATETM, to measure women's participation in medical
      decisions during the reproductive process. DESIGN: Cross-sectional study to adapt
      and validate the instrument CollaboRATETM. LOCATION: Maternity units in Santiago,
      Chile. PARTICIPANTS: Puerperal women in maternity units of three public
      hospitals. METHOD: Translation and back-translation, cultural and linguistic
      relevance with service users and final revision by experts. Study for validation
      with 90 puerperal women. RESULTS: The Chilean version of CollaboRATETM
      demonstrated to be a reliable instrument to capture the degree of patients'
      participation in medical decision-making. Cronbach alpha was above 0.89.
      CONCLUSIONS: This study provides the first instrument to capture the prevalence
      of SDM in a Latin American country. This instrument will be critical in future
      research efforts that seek to explore to what extent people are being involved in
      the decisions related to their healthcare.

PMID- 28760345
TI  - Dynamics of actinotrichia regeneration in the adult zebrafish fin.
AB  - The skeleton of adult zebrafish fins comprises lepidotrichia, which are dermal
      bones of the rays, and actinotrichia, which are non-mineralized spicules at the
      distal margin of the appendage. Little is known about the regenerative dynamics
      of the actinotrichia-specific structural proteins called Actinodins. Here, we
      used immunofluorescence analysis to determine the contribution of two paralogous
      Actinodin proteins, And1/2, in regenerating fins. Both proteins were detected in
      the secretory organelles in the mesenchymal cells of the blastema, but only And1
      was detected in the epithelial cells of the wound epithelium. The analysis of
      whole mount fins throughout the entire regenerative process and longitudinal
      sections revealed that And1-positive fibers are complementary to the
      lepidotrichia. The analysis of another longfin fish, a gain-of-function mutation
      in the potassium channel kcnk5b, revealed that the long-fin phenotype is
      associated with an extended size of actinotrichia during homeostasis and
      regeneration. Finally, we investigated the role of several signaling pathways in
      actinotrichia formation and maintenance. This revealed that the pulse-inhibition
      of either TGFbeta/Activin-betaA or FGF are sufficient to impair deposition of
      Actinodin during regeneration. Thus, the dynamic turnover of Actinodin during fin
      regeneration is regulated by multiple factors, including the osteoblasts, growth
      rate in a potassium channel mutant, and instructive signaling networks between
      the epithelium and the blastema of the regenerating fin.

PMID- 28760346
TI  - A defect in the mitochondrial protein Mpv17 underlies the transparent casper
      zebrafish.
AB  - The casper strain of zebrafish is widely used in studies ranging from cancer to
      neuroscience. casper offers the advantage of relative transparency throughout
      adulthood, making it particularly useful for in vivo imaging by epifluorescence,
      confocal, and light sheet microscopy. casper was developed by selective breeding
      of two previously described recessive pigment mutants: 1) nacre, which harbors an
      inactivating mutation of the mitfa gene, rendering the fish devoid of pigmented
      melanocytes; and 2) roy orbison, a mutant with a so-far unidentified genetic
      cause that lacks reflective iridophores. To clarify the molecular nature of the
      roy orbison mutation, such that it can inform studies using casper, we undertook
      an effort to positionally clone the roy orbison mutation. We find that roy
      orbison is caused by an intronic defect in the gene mpv17, encoding an inner
      mitochondrial membrane protein that has been implicated in the human
      mitochondrial DNA depletion syndrome. The roy orbison mutation is phenotypically
      and molecularly remarkably similar to another zebrafish iridophore mutant called
      transparent. Using Cas9-induced crispants and germline mutants with a disrupted
      mpv17 open reading frame, we show in trans-heterozygote embryos that new
      frameshift alleles of mpv17, roy orbison, and transparent fail to complement each
      other. Our work provides genetic evidence that both roy orbison and transparent
      affect the mpv17 locus by a similar if not identical genetic lesion.
      Identification of mpv17 mutants will allow for further work probing the
      relationship between mitochondrial function and pigmentation, which has to date
      received little attention.

PMID- 28760347
TI  - Genome segments encoding capsid protein-like variants of Pyrus pyrifolia cryptic
      virus.
AB  - According to previous studies, three double-stranded (ds) RNA molecules (dsRNA1,
      2, and 3) detected in Japanese pear are transmitted to the next generation with
      high frequency through both ovules and pollen. Nucleotide sequence analysis of
      dsRNA1-encoding RNA-dependent RNA polymerase (RdRp) has suggested that these
      dsRNAs are related to a cryptovirus named Pyrus pyrifolia cryptic virus (PpCV).
      In this study, purified dsRNA prepared from a PpCV-infected Japanese pear
      cultivar was subjected to next-generation deep sequencing. This sequencing
      generated two de novo assembled contigs corresponding to dsRNA2 and 3, with BLAST
      analysis of the predicted amino acid sequences indicating homology to capsid
      proteins (CPs) of the cryptoviruses persimmon cryptic virus and Sinapis alba
      cryptic virus 1, respectively. Relationships between the two contigs and dsRNA2
      and 3 were confirmed by northern blot hybridization with probes generated using
      primers designed from the assembled contigs. Rapid amplification of cDNA ends
      analyses of 5'- and 3'-terminal sequences of dsRNA2 and 3 revealed that these two
      dsRNAs consist of 1523 and 1481bp, respectively. The 5'-terminal sequences
      (AGAAUUUC) of dsRNA1, 2 and 3 were found to be conserved. Phylogenetic analysis
      of deduced amino acid sequences of the two CP-like variants indicated that PpCV
      belongs to Deltapartitivirus (Partitiviridae). Our results imply that PpCV is tri
      segmented.

PMID- 28760348
TI  - CRISPR-Cas based antiviral strategies against HIV-1.
AB  - In bacteria and archaea, the clustered regularly interspaced short palindromic
      repeats (CRISPR) and associated proteins (Cas) confer adaptive immunity against
      exogenous DNA elements. This CRISPR-Cas system has been turned into an effective
      tool for editing of eukaryotic DNA genomes. Pathogenic viruses that have a double
      stranded DNA (dsDNA) genome or that replicate through a dsDNA intermediate can
      also be targeted with this DNA editing tool. Here, we review how CRISPR-Cas was
      used in novel therapeutic approaches against the human immunodeficiency virus
      type-1 (HIV-1), focusing on approaches that aim to permanently inactivate all
      virus genomes or to prevent viral persistence in latent reservoirs.

PMID- 28760349
TI  - The effect of sequential information on consumers' willingness to pay for
      credence food attributes.
AB  - The use of experimental methods to determine consumers' willingness to pay for
      "quality" food has been gaining importance in scientific research. In most of the
      empirical literature on this issue the experimental design starts with blind
      tasting, after which information is introduced. It is assumed that this approach
      allows consumers to elicit the real value that they attach to each of the
      features added through specific information. In this paper, the starting
      hypothesis is that this technique overestimates the weight of the features
      introduced by information in consumers' willingness to pay when compared to a
      real market situation, in which consumers are confronted with all the information
      at once. The data obtained through contingent valuation in an in-store setting
      was used to estimate a hedonic model aiming at assessing consumers' willingness
      to pay (WTP) for the feature "geographical origin of the variety" of pears and
      apples in different information scenarios: i) blind tasting followed by extrinsic
      information and ii) full information provided at once. The results show that, in
      fact, features are more valued when gradually added to background information
      than when consumers receive all the information from the beginning.

PMID- 28760350
TI  - An approach towards accountability: suggestions for increased reproducibility in
      surgical destabilization of medial meniscus (DMM) models.

PMID- 28760351
TI  - Therapeutic strategies for locally recurrent and metastatic de-differentiated
      liposarcoma with herpes simplex virus-thymidine kinase-expressing mesenchymal
      stromal cells.
AB  - BACKGROUND AIMS: Major challenges in de-differentiated liposarcoma (DDLPS)
      therapy are the high rate of sequential recurrence (>80%) and metastasis (20-30%)
      following surgical removal. However, well-defined therapeutic strategies for this
      rare malignancy are lacking and are critically needed. METHODS: We investigated a
      new approach to DDLPS therapy with mesenchymal stromal cells expressing herpes
      simplex virus-thymidine kinase (MSC-TK). In an effort to evaluate this efficacy,
      in vitro cytotoxicity of MSC-TK against DDLPS cells was analyzed using an
      apoptosis assay. For pre-clinical study, the MSC-TK-induced reduction in
      recurrence and metastasis was validated in a recurrent DDLPS model after the
      macroscopic complete resection and lung metastasis DDLPS model. RESULTS: MSC-TK
      induced apoptosis in DDLPS cells by bystander effects via gap junction
      intracellular communication (GJIC) of toxic ganciclovir (GCV). Recurrent DDLPS
      models following no residual tumor/microscopic tumor resection and lung
      metastasis DDLPS models were established, which suggested clinical relevance. MSC
      TK markedly reduced locoregional recurrence rates and prolonged recurrence-free
      survival, thus increasing overall survival in the recurrent DDLPS model. MSC-TK
      followed by GCV treatment yielded a statistically significant reduction in early-
      and advanced-stage lung metastasis. DISCUSSION: This therapeutic strategy may
      serve as an alternative or additional strategy by applying MSC-TK to target
      residual tumors following surgical resection, thus reducing local relapse and
      metastasis in these patients.

PMID- 28760352
TI  - Image-guided percutaneous intralesional administration of mesenchymal stromal
      cells in subjects with chronic complete spinal cord injury: a pilot study.
AB  - BACKGROUND AIMS: The potential of cell therapies to improve neurological function
      in subjects with spinal cord injury (SCI) is currently under investigation. In
      this context, the choice of cell type, dose, route and administration regimen are
      key factors. Mesenchymal stromal cells (MSCs) can be easily obtained, expanded
      and are suitable for autologous transplantation. Here we conducted a pilot study
      that evaluated safety, feasibility and potential efficacy of intralesional MSCs
      transplantation performed through image-guided percutaneous injection, in
      subjects with chronic complete SCI. METHODS: Five subjects with chronic traumatic
      SCI (>6 months), at thoracic level, classified as American Spinal Cord Injury
      Association impairment scale (AIS) grade A, complete injury, were included.
      Somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI)
      and urodynamics were assessed before and after treatment. Autologous MSCs were
      injected directly into the lesion site through percutaneous injection guided by
      computerized tomography (CT). RESULTS: Tomography-guided percutaneous cell
      transplantation was a safe procedure without adverse effects. All subjects
      displayed improvements in spinal cord independence measure (SCIM) scores and
      functional independence measure (FIM), mainly due to improvements in bowel
      movements and regularity. Three subjects showed improved sensitivity to tactile
      stimulation. Two subjects improved AIS grade to B, incomplete injury, although
      this was sustained in only one of them during the study follow-up. CONCLUSION:
      Autologous bone marrow MSC transplantation, performed through CT-guided
      percutaneous injection, was shown to be safe and feasible. Further studies are
      required to demonstrate efficacy of this therapeutic scheme.

PMID- 28760353
TI  - Evaluation of endothelial dysfunction in patients with nonalcoholic fatty liver
      disease: Association of selenoprotein P with carotid intima-media thickness and
      endothelium-dependent vasodilation.
AB  - BACKGROUND: In patients with NAFLD, there is an increased risk of cardiovascular
      disease (CVD). Selenoprotein P (SelP), a hepatokine, is associated with insulin
      resistance (IR) and serum SelP was found to be elevated in patients with NAFLD.
      AIM: This study aimed to determine the risk of CVD in NAFLD patients and the
      association of serum SelP levels with this NAFLD related CVD risk. METHODS:
      Ninety-three patients with NAFLD and 37 healthy controls were included in the
      study. Complete blood count, C-reactive protein (CRP), fasting glucose, serum
      lipid levels, and SelP levels were tested from fasting blood samples. Moreover,
      body mass index (BMI), HOMA-IR, carotid intima-media thickness (cIMT) and flow
      mediated dilatation (FMD) were measured. RESULTS: In patients with NAFLD, the FMD
      ratio was significantly lower than in controls (P=0.027). cIMT measurements were
      similar in both groups (P=0.996). Serum SelP levels were significantly higher
      than controls (P<0.001). SelP levels were significantly correlated with BMI,
      fasting glucose, LDL-cholesterol and HOMA-IR (r=0.395, P<0.001; r=0.322, P=0.002;
      r=0.353, P<0.001; r=0.521, P<0.001, respectively). Also, SelP levels were
      significantly lower and correlated with FMD (r=-0.674, P<0.001). SelP, ESR and
      CRP were significantly higher (P<0.05) and FMD ratios were significantly lower
      (P<0.05) in patients with nonalcoholic steatohepatitis (NASH) when compared to
      patients with simple steatosis. CONCLUSION: These results suggest that in young
      NAFLD patients without additional comorbidities, there is an increased risk of
      CVD. FMD may be a better predictor for assessment of CVD risk when compared with
      cIMT. We assume that there could also be an important role of SelP in the
      pathogenesis of NASH.

PMID- 28760354
TI  - T2 MR imaging vs. computational modeling of human articular cartilage tissue
      functionality.
AB  - The detection of early stages of cartilage degeneration remains diagnostically
      challenging. One promising non-invasive approach is to functionally assess the
      tissue response to loading by serial magnetic resonance (MR) imaging in terms of
      T2 mapping under simultaneous mechanical loading. As yet, however, it is not
      clear which cartilage component contributes to the tissue functionality as
      assessed by quantitative T2 mapping. To this end, quantitative T2 maps of
      histologically intact cartilage samples (n=8) were generated using a clinical 3.0
      T MR imaging system. Using displacement-controlled quasi-static indentation
      loading, serial T2 mapping was performed at three defined strain levels and
      loading-induced relative changes were determined in distinct regions-of-interest.
      Samples underwent conventional biomechanical testing (by unconfined compression)
      as well as histological assessment (by Mankin scoring) for reference purposes.
      Moreover, an anisotropic hyperelastic constitutive model of cartilage was
      implemented into a finite element (FE) code for cross-referencing. In efforts to
      simulate the evolution of compositional and structural intra-tissue changes under
      quasi-static loading, the indentation-induced changes in quantitative T2 maps
      were referenced to underlying changes in cartilage composition and structure.
      These changes were parameterized as cartilage fluid, proteoglycan and collagen
      content as well as collagen orientation. On a pixel-wise basis, each individual
      component correlation with T2 relaxation times was determined by Spearman's rhos
      and significant correlations were found between T2 relaxation times and all four
      tissue parameters for all indentation strain levels. Thus, the biological changes
      in functional MR Imaging parameters such as T2 can further be characterized to
      strengthen the scientific basis of functional MRI techniques with regards to
      their perspective clinical applications.

PMID- 28760355
TI  - Decreasing readmissions by focusing on complications and underlying reasons.
AB  - BACKGROUND: To analyze demographics and outcomes of patients focusing on 30-day
      readmission status and identify procedure-specific risk factors. METHODS:
      Patients undergoing abdominal colorectal surgery (2011-2013) were identified
      Demographics and outcomes including in-hospital complications were compared based
      on readmission status. RESULTS: A total of 6637 patients were identified with a
      mean age of 51.2(+/-17.1) years. Seven hundred and seventy five(11.7%) patients
      were readmitted at least once within 30-day. The most common index procedures
      related to readmission were stoma closure (n = 127/775, 16.4%) and total
      colectomy (n = 105/775, 13.6%). Readmitted patients had longer length of index
      hospital stay (LOS)(8.2 +/- 5.9 vs 7.9 +/- 6.9 days,p < 0.001) and operative
      time(167 +/- 104 vs 144 +/- 95 min, p < 0.001), higher intraoperative(2% vs 1%,p
      = 0.04) and in-hospital complication rates(36% vs 28%,p < 0.001). Main reasons
      for readmissions were gastrointestinal-related causes(n = 222, 29%), small bowel
      obstruction (n = 133,17%), wound-related complications(n = 108,14%), and
      dehydration(n = 93,12%). Median readmission LOS was 4(1-71)days and 54%(n = 407)
      of readmissions occurred within 7 days of discharge. CONCLUSION: Increased
      postoperative complications may be the main preventable underlying reason for
      increased risk of hospital readmission after colorectal surgery. Preventive
      measures to decrease complications and actions to identify high risk patients for
      complications would help to reduce readmissions.

PMID- 28760356
TI  - Unplanned readmission and outpatient examination 90-days after acute appendectomy
      in adults.
AB  - BACKGROUND: The aim of this study was to determine the frequency and indications
      for unplanned readmission and outpatient examination after acute appendectomy.
      METHODS: Adults who underwent acute appendectomy from 2008-2013 were included in
      the study and events occurring within 90-days from discharge recorded. RESULTS: A
      total of 710 patients underwent surgery. The appendix was removed in 622 patients
      and post-discharge contact occurred in 99 (15.9%): readmission in 60 (9.6%),
      outpatient examination in 39 (6.3%). The main reasons for post-discharge contact
      were infection (n = 25; intraabdominal, n = 16; superficial) and abdominal pain
      of uncertain cause (n = 25). Use of prophylactic antibiotics was associated with
      lower rates of contact, 8.5% versus 20.9% (p = 0.006), respectively. Removal of
      non-inflamed appendix was borderline associated with higher rates of contact,
      21.7% versus 8.0% (if left in-situ; p = 0.058), respectively. CONCLUSIONS: A
      substantial number of patients underwent readmission or outpatient examination
      within 90-days after appendectomy in the current study. The procedure is common
      and attempts to prevent readmissions are important. Correct use of antibiotics
      and not removing a non-inflamed appendix may be key points.

PMID- 28760357
TI  - Regional differences for pancreaticoduodenectomy in Florida: Location matters.
AB  - INTRODUCTION: Regionalization of care raises potential for differences in cost of
      care and outcome. This study was undertaken to determine if costs and outcome
      after pancreaticoduodenectomy vary by region in Florida, and whether costs and
      outcome are related. METHODS: Inpatient data for pancreaticoduodenectomy in
      Florida during 2010-2012 were obtained from the Florida Agency for Health Care
      Administration. Seven geographically different regions were designated based on
      "cost of living index" and "urban to rural population ratio". Hospital costs,
      LOS, in-hospital mortality, and the frequency with which surgeons performed
      pancreaticoduodenectomy were evaluated for these regions. RESULTS: Median
      hospital costs for pancreaticoduodenectomy by region ranged from $101,436
      $214,971. Median hospital costs by region correlated positively with LOS (p <
      0.0001) and in-hospital mortality (p < 0.0001), and negatively with the frequency
      of pancreaticoduodenectomies performed by high-volume surgeons (p < 0.0001).
      CONCLUSIONS: There are regional differences for hospital costs and outcome with
      pancreaticoduodenectomy in Florida. Regions with lower costs had more
      pancreaticoduodenectomies performed by high-volume surgeons, shorter LOS, and
      lower in-hospital mortality rates. Regional differences in cost and quality-of
      care need to be studied and abrogated to provide uniform optimal care.

PMID- 28760358
TI  - Acaricidal, pediculicidal and larvicidal activity of synthesized ZnO
      nanoparticles using Momordica charantia leaf extract against blood feeding
      parasites.
AB  - The aim of the present study was to evaluate the acaricidal, pediculicidal and
      larvicidal effect of synthesized zinc oxide nanoparticles (ZnO NPs) using
      Momordica charantia leaf extract against the larvae of Rhipicephalus (Boophilus)
      microplus, adult of Pediculus humanus capitis, and the larvae of Anopheles
      stephensi, Culex quinquefasciatus. The ZnO NPs were characterized by using UV,
      XRD, FTIR and SEM-EDX. The SEM image confirms that the synthesized nanoparticles
      were spherical in shape with a size of 21.32 nm. The results of GC-MS analysis
      indicates the presence of the major compound of Nonacosane (C29H60) in the M.
      charantia leaf extract. Cattle tick, head lice and mosquito larvae were exposed
      to a varying concentrations of the synthesized ZnO NPs and M. charantia leaf
      extract for 24 h. Compared to the leaf aqueous extract, biosynthesized ZnO NPs
      showed higher toxicity against R. microplus, P. humanus capitis, An. stephensi,
      and Cx. Quinquefasciatus with the LC50 values of 6.87, 14.38, 5.42, and 4.87
      mg/L, respectively. The findings revealed that synthesized ZnO NPs possess
      excellent anti-parasitic activity. These results suggest that the green
      synthesized ZnO NPs has the potential to be used as an ideal ecofriendly approach
      for the control of R. microplus, P. humanus capitis and the mosquito larvae of
      An. Stephensi and Cx. quinquefasciatus.

PMID- 28760359
TI  - Assessment of in vitro killing assays for detecting praziquantel-induced death in
      Posthodiplostomum minimum metacercariae.
AB  - Control of parasitic infections may be achieved by eliminating developmental
      stages present within intermediate hosts, thereby disrupting the parasite life
      cycle. For several trematodes relevant to human and veterinary medicine, this
      involves targeting the metacercarial stage found in fish intermediate hosts.
      Treatment of fish with praziquantel is one potential approach for targeting the
      metacercaria stage. To date, studies investigating praziquantel-induced
      metacercarial death in fish rely on counting parasites and visually assessing
      morphology or movement. In this study, we investigate quantitative methods for
      detecting praziquantel-induced death using a Posthodiplostomum minimum model. Our
      results revealed that propidium iodide staining accurately identified
      praziquantel-induced death and the level of staining was proportional to the
      concentration of praziquantel. In contrast, detection of ATP, resazurin
      metabolism, and trypan blue staining were poor indicators of metacercarial death.
      The propidium iodide method offers an advantage over simple visualization of
      parasite movement and could be used to determine EC50 values relevant for
      comparison of praziquantel sensitivity or resistance.

PMID- 28760360
TI  - Autophagy induced by infectious hematopoietic necrosis virus inhibits
      intracellular viral replication and extracellular viral yields in epithelioma
      papulosum cyprini cell line.
AB  - Infectious hematopoietic necrosis virus (IHNV) is a common pathogen that causes
      severe disease in the salmonid aquaculture industry. Recent work demonstrated
      that autophagy plays an important role in pathogen invasion by activating innate
      and adaptive immunity. This study investigated the relationship between IHNV and
      autophagy in epithelioma papulosum cyprini cells. The electron microscopy results
      show that IHNV infection can induce typical autophagosomes which are
      representative structures of autophagy activation. The punctate accumulation of
      green fluorescence-tagged microtubule-associate protein 1 light chain 3 (LC3) and
      the protein conversion from LC3-I to LC3-II were respectively confirmed by
      confocal fluorescence microscopy and western blotting. Furthermore, the effects
      of autophagy on IHNV replication were also clarified by altering the autophagy
      pathway. The results showed that rapamycin induced autophagy can inhibit both
      intracellular viral replication and extracellular viral yields, while autophagy
      inhibitor produced the opposite results. These findings demonstrated that
      autophagy plays an antiviral role during IHNV infection.

PMID- 28760361
TI  - Do Performance-Safety Tradeoffs Cause Hypometric Metabolic Scaling in Animals?
AB  - Hypometric scaling of aerobic metabolism in animals has been widely attributed to
      constraints on oxygen (O2) supply in larger animals, but recent findings
      demonstrate that O2 supply balances with need regardless of size. Larger animals
      also do not exhibit evidence of compensation for O2 supply limitation. Because
      declining metabolic rates (MRs) are tightly linked to fitness, this provides
      significant evidence against the hypothesis that constraints on supply drive
      hypometric scaling. As an alternative, ATP demand might decline in larger animals
      because of performance-safety tradeoffs. Larger animals, which typically
      reproduce later, exhibit risk-reducing strategies that lower MR. Conversely,
      smaller animals are more strongly selected for growth and costly neurolocomotory
      performance, elevating metabolism.

PMID- 28760362
TI  - The Addition of Automated Breast Ultrasound to Mammography in Breast Cancer
      Screening Decreases Stage at Diagnosis.
AB  - RATIONALE AND OBJECTIVES: This study aimed to determine the best screening
      strategy using automated whole-breast ultrasound and mammography in women with
      increased breast density or an elevated risk of breast cancer. MATERIALS AND
      METHODS: After an institutional review board waiver was obtained, a retrospective
      review of 122 cancer cases diagnosed in 3435 women with increased breast density
      or an elevated risk of breast cancer, screened with mammography and supplemental
      automated whole-breast ultrasound, was performed. The imaging modality on which
      each cancer was seen was noted. Screening strategies were postulated. For each
      screening strategy, rates of advanced cancer diagnosis, with 95% confidence
      limits, are calculated using the Clopper-Pearson method. Differences in outcomes
      were calculated using Cochrane Q test and McNemar test for paired observations.
      Results were expressed for all stages of cancer and for invasive cancers only.
      RESULTS: When all cancer stages are considered, mammographic screening reduces
      advanced cancers by 31% over no screening. Ultrasound-only screening results in a
      32% reduction. The combination of mammographic and ultrasound screening reduces
      advanced cancers by 40% (P < .05). Compared to mammographic screening,
      mammographic plus ultrasound screening reduces advanced-stage cancers by 5.7% (P
      = 0.03) for all stages and 10.8% (P = 0.02) for invasive cancers. CONCLUSIONS:
      For women with increased breast density or who are at high risk of developing
      breast cancer, a combination of screening mammography and whole-breast automated
      ultrasound is superior to mammographic screening. Screening ultrasound alone is
      also an effective screening strategy.

PMID- 28760363
TI  - Strategies for Decreasing Screening Mammography Recall Rates While Maintaining
      Performance Metrics.
AB  - RATIONALE AND OBJECTIVE: This study aimed to determine the impact of
      interventions designed to reduce screening mammography recall rates on screening
      performance metrics. MATERIALS AND METHODS: We assessed baseline performance for
      full-field digital mammography (FFDM) and digital breast tomosynthesis
      mammography (DBT) for a 3-year period before intervention. The first intervention
      sought to increase awareness of recalls from screening mammography. Breast
      imagers discussed their perceptions regarding screening recalls and were required
      to review their own recalled cases, including outcomes of diagnostic evaluation
      and biopsy. The second intervention implemented consensus double reading of all
      recalls, requiring two radiologists to agree if recall was necessary. Recall
      rates, cancer detection rates, and positive predictive value 1 (PPV1) were
      compared before and after each intervention. RESULTS: The baseline recall rate,
      cancer detection rate, and PPV1 were 11.1%, 3.8/1000, and 3.4%, respectively, for
      FFDM, and 7.6%, 4.8/1000, and 6.0%, respectively, for DBT. Recall rates decreased
      significantly to 9.2% for FFDM and to 6.6% for DBT after the first intervention
      promoting awareness, as well as to 9.9% for FFDM after the second intervention
      implementing group consensus. PPV1 increased significantly to 5.7% for FFDM and
      to 9.0% for DBT after the second intervention. Cancer detection rate did not
      significantly change with the implementation of these interventions. An average
      of 2.3 minutes was spent consulting for each recall. CONCLUSION: Reduction in
      recall rates is desirable, provided performance metrics remain favorable. Our
      interventions improved performance and could be implemented in other breast
      imaging settings.

PMID- 28760364
TI  - Does the Oral "Mock Board" Examination Still Have a Role as a Training Tool?
AB  - RATIONALE AND OBJECTIVES: The American Board of Radiology has adopted a new
      standardized board examination and the traditional oral examination has been
      abandoned. Although many programs have changed their educational efforts to
      reflect the new test format, some faculty members and residents have expressed a
      desire to keep an oral examination as a component of education and evaluation in
      radiology residency programs. MATERIALS AND METHODS: An oral comprehensive
      examination including all the appropriate subspecialties was administered to each
      second year and third year resident in our training program by faculty members.
      Both the resident examinees and faculty examiners were surveyed after the
      examination to gauge the perceived value of the experience. RESULTS: Residents
      were divided in their perceptions of the fairness and utility of an oral
      examination as a tool to aid in board preparation and as an assessment of their
      knowledge and communication skill. Faculty members were universal in their
      endorsement of the oral examination and suggested continued use of the technique.
      CONCLUSIONS: Residents and faculty members have differing perceptions of an oral
      examination delivered during training to assess knowledge and communication
      skill. The value of an oral examination in providing actionable feedback to
      trainees and the possibility of detecting struggling residents made it useful in
      our training program, and it thus it has been implemented for future years.
      Whether resident performance measured by this technique is predictive of success
      on American Board of Radiology examinations remains unclear.

PMID- 28760365
TI  - Corrigendum to "miR-125a-5p Modulates Phenotypic Switch of Vascular Smooth Muscle
      Cells by Targeting ETS-1" (J. Mol. Biol. Jun 16 2017;429(12):1817-1828).

PMID- 28760367
TI  - Effects of metformin on endometrial cancer: Systematic review and meta-analysis.
AB  - BACKGROUND: Endometrial cancer is one of the most common gynecological cancers,
      which is frequently preceded by atypical endometrial hyperplasia, a premalignant
      lesion. Metformin, an antidiabetic drug, has emerged as a new adjunctive strategy
      for different cancer types, including endometrial cancer. This systematic review
      and meta-analysis aimed to evaluate the effects of metformin in atypical
      endometrial hyperplasia and endometrial cancer patients. METHODS: The search was
      conducted on January 2017 and the articles were collected in Cochrane, LILACS,
      PubMed, Scopus and Web of Science. A grey literature search was undertaken using
      Google SCHOLAR, ProQuest and Open Grey. Nineteen studies were included, which
      contained information about the following outcomes: reversal of atypical
      endometrial hyperplasia, cellular proliferation biomarkers expression and overall
      survival in metformin-users compared to non-users. RESULTS: Metformin was
      associated with reversion of atypical endometrial hyperplasia to a normal
      endometrial, and with decreased cell proliferation biomarkers staining, from
      51.94% (CI=36.23% to 67.46%) to 34.47% (CI=18.55% to 52.43%). However, there is a
      high heterogeneity among studies. Metformin-users endometrial cancer patients had
      a higher overall survival compared to non-metformin users and non-diabetic
      patients (HR=0.82; CI: 0.70-0.95; p=0.09, I2=40%). CONCLUSION: Regardless the
      high heterogeneity of the analyzed studies, the present review suggests that
      adjunct metformin treatment may assist in the reversal of atypical endometrial
      hyperplasia to normal endometrial histology, in the reduction of cell
      proliferation biomarkers implicated in tumor progression, and in the improvement
      of overall survival in endometrial cancer. Further work on prospective controlled
      trials designed to address the effects of adjunct metformin on clinical outcomes
      is necessary for definite conclusions.

PMID- 28760366
TI  - Intentional Self-inflicted Burn Injuries: Review of the Literature.
AB  - BACKGROUND: Intentional self-inflicted burn injuries are a rare occurrence in the
      United States, but they represent a considerable portion of all burn injuries in
      the developing world. Compared to nonintentional burns, patients with intentional
      self-inflicted burns have increased rates of higher total body surface area
      involvement and associated complications, including overall mortality. METHODS:
      We present 2 representative cases and review the available literature on the
      topic of self-inflicted burns. We review epidemiologic, social, and cultural
      factors of importance, and also provide an overview of most common psychiatric
      pathologies encountered in patients with self-inflicted burns. RESULTS: The
      patient demographics and motivation for intentional self-inflicted burn injuries
      differ considerably across the world. Although self-immolation is commonly
      associated with women experiencing domestic stress in the developing world, most
      cases of self-immolation in higher-income countries are males. Psychiatric
      pathologies, including primary mood and thought disorders and substance use, play
      a significant component in latter cases, while most patients in the developing
      world lack any premorbid psychiatric diagnosis, or carry diagnosis of adjustment
      disorder. CONCLUSIONS: Nonlethal self-burns present a distinct subset of
      intentional self-burn injuries, often occurring in the context of significant
      personality pathology, or with potential secondary gain.

PMID- 28760368
TI  - Is adjuvant chemotherapy beneficial for surgical stage I ovarian clear cell
      carcinoma?
AB  - : Objective To assess the impact of adjuvant chemotherapy on survival in patients
      with surgical stage I ovarian clear cell carcinoma (OCCC). METHODS: Data
      collection and analysis of surgical stage I OCCC patients treated at two tertiary
      cancer centers was performed. Descriptive statistics, univariate and
      multivariable analyses and Kaplan-Meier survival probability estimates were
      completed. RESULTS: Sixty stage I OCCC patients who underwent comprehensive
      surgical staging were identified. 29 patients received adjuvant chemotherapy and
      31 did not. Median follow-up was 4.96 (0.4-16.4) years. The 5-year disease
      specific survival (DSS) was 84.2%: 95% for stage IA and 76% for stage IB+IC
      (p=0.16). There were 11 disease specific deaths: 7 in the no adjuvant
      chemotherapy group (NACG) and 4 in the adjuvant chemotherapy group (ACG). 5-year
      DSS was 84.2%: 74% in NACG and 93% in ACG, (p=0.13). Seventeen patients recurred:
      11 in NACG and 6 in ACG (p=0.2). None of the 21 patients with stage I known
      negative cytology recurred. 5-year PFS was 74%: 58% in NACG and 86% in ACG
      (p=0.035). On univariate analysis, no-adjuvant chemotherapy and positive cytology
      were poor prognostic factors for PFS: HR=2.36, p=0.04 and HR=3.1, p=0.027,
      respectively. After adjusting for positive cytology, no-adjuvant chemotherapy was
      still found to significantly correlate with a worse PFS (HR=4, p=0.01).
      CONCLUSION: Our data supports the use of adjuvant chemotherapy for surgical stage
      I OCCC. As no patients in our cohort with surgical stage I known negative
      cytology recurred, more research on the benefit of adjuvant chemotherapy in this
      group is warranted.

PMID- 28760369
TI  - Towards systems metabolic engineering in Pichia pastoris.
AB  - The methylotrophic yeast Pichia pastoris is firmly established as a host for the
      production of recombinant proteins, frequently outperforming other heterologous
      hosts. Already, a sizeable amount of systems biology knowledge has been acquired
      for this non-conventional yeast. By applying various omics-technologies,
      productivity features have been thoroughly analyzed and optimized via genetic
      engineering. However, challenging clonal variability, limited vector repertoire
      and insufficient genome annotation have hampered further developments. Yet, in
      the last few years a reinvigorated effort to establish P. pastoris as a host for
      both protein and metabolite production is visible. A variety of compounds from
      terpenoids to polyketides have been synthesized, often exceeding the productivity
      of other microbial systems. The clonal variability was systematically
      investigated and strategies formulated to circumvent untargeted events, thereby
      streamlining the screening procedure. Promoters with novel regulatory properties
      were discovered or engineered from existing ones. The genetic tractability was
      increased via the transfer of popular manipulation and assembly techniques, as
      well as the creation of new ones. A second generation of sequencing projects
      culminated in the creation of the second best functionally annotated yeast
      genome. In combination with landmark physiological insights and increased output
      of omics-data, a good basis for the creation of refined genome-scale metabolic
      models was created. The first application of model-based metabolic engineering in
      P. pastoris showcased the potential of this approach. Recent efforts to establish
      yeast peroxisomes for compartmentalized metabolite synthesis appear to fit
      ideally with the well-studied high capacity peroxisomal machinery of P. pastoris.
      Here, these recent developments are collected and reviewed with the aim of
      supporting the establishment of systems metabolic engineering in P. pastoris.

PMID- 28760370
TI  - What NMR can do in the biopharmaceutical industry.
AB  - Nuclear magnetic resonance (NMR) spectroscopy has a unique capability to probe
      the primary and higher order molecular structure and the structural dynamics of
      biomolecules at an atomic resolution, and this capability has been greatly
      fortified over the last five decades by an astonishing NMR instrumental and
      methodological development. Because of these factors, NMR has become a primary
      tool for the structure investigation of biomolecules, spawning a whole scientific
      subfield dedicated to the subject. This role of NMR is by now well established
      and broadly appreciated, especially in the context of academic research dealing
      with proteins that are purified and isotope-labeled in order to facilitate the
      necessary sophisticated multidimensional NMR measurements. However, the more
      recent industrial development, manufacturing, and quality control of
      biopharmaceuticals provide a different framework for NMR. For example, protein
      drug substances are not isotope-labeled and are present in a medium of
      excipients, which make structural NMR measurements much more difficult. On the
      other hand, biotechnology involves many other analytical requirements that can be
      efficiently addressed by NMR. In this respect the scope and limitations of NMR
      are less well understood. Having the non-expert reader in mind, herein we wish to
      highlight the ways in which modern NMR can effectively support biotechnological
      developments. Our focus will be on biosimilar proteins, pointing out certain
      cases where its use is probably essential. Based partly on literature data, and
      partly on our own hands-on experience, this paper is intended to be a guide for
      choosing the proper NMR approach for analytical questions concerning the
      structural comparability of therapeutic proteins, monitoring technology-related
      impurities, protein quantification, analysis of spent media, identification of
      extractable and leachable components, etc. Also, we focus on critical
      considerations, particularly those coming from drug authority guidelines, which
      limit the use of the well-established NMR tools in everyday practice.

PMID- 28760371
TI  - Visualization and simulation of density driven convection in porous media using
      magnetic resonance imaging.
AB  - Magnetic resonance imaging is used to observe solute transport in a 40cm long,
      26cm diameter sand column that contained a central core of low permeability
      silica surrounded by higher permeability well-sorted sand. Low concentrations
      (2.9g/L) of Magnevist, a gadolinium based contrast agent, produce density driven
      convection within the column when it starts in an unstable state. The unstable
      state, for this experiment, exists when higher density contrast agent is present
      above the lower density water. We implement a numerical model in OpenFOAM to
      reproduce the observed fluid flow and transport from a density difference of
      0.3%. The experimental results demonstrate the usefulness of magnetic resonance
      imaging in observing three-dimensional gravity-driven convective-dispersive
      transport behaviors in medium scale experiments.

PMID- 28760372
TI  - [Histoseminar on Inflammatory Bowel Diseases (IBD): Cases no. 07 and 08].

PMID- 28760373
TI  - Advantages of external hybrid fixators for treating Schatzker V-VI tibial plateau
      fractures: A retrospective study of 40 cases.
AB  - INTRODUCTION: Proximal tibia fractures make up 1% of all fractures in adults. The
      fractures classified as Schatzker V and VI fractures can compromise knee
      structure and function. They are challenging to treat and often have
      complications. While plate fixation is the gold standard, the resulting infection
      rate has led us to favor external hybrid fixation. The aims of this study were to
      assess the radiographic and functional outcomes along with the complication rate
      when using this method and to compare them to historical plate fixation data.
      MATERIAL AND METHODS: This was a retrospective study of 40 patients. The
      complications, quality of reduction, IKS, Lysholm and Rasmussen functional scores
      at the latest follow-up and factors affecting the functional outcome were
      evaluated. These parameters were compared to published results from plate
      fixation studies. RESULTS: The deep infection rate was 2.5%. The union rate was
      80%. Satisfactory reduction was obtained in 70% of cases; however, 52% of
      patients had malunion. The mean IKS score was 73.74, the mean Rasmussen score was
      22.85 and the mean Lysholm score was 75.53. Age, reduction at latest follow-up,
      mechanical axis and anteroposterior laxity had a significant effect on the
      functional outcome. DISCUSSION: Despite the malunion rate being higher than other
      studies, the functional outcomes were nearly identical based on the variables
      measured. There are several advantages associated with using a hybrid external
      fixator: shorter operative time, less bleeding, shorter hospital stays and lower
      infection rate. CONCLUSION: Hybrid external fixation is a reliable fracture
      fixation method that leads to satisfactory functional outcomes, while reducing
      the infection rate and allowing arthroplasty to be performed in the future if
      needed.

PMID- 28760374
TI  - Ropivacaine alters the mechanical properties of hamstring tendons: In vitro
      controlled mechanical testing of tendons from living donors.
AB  - OBJECTIVE: Intraarticular or periarticular injection of ropivacaine (RI) is an
      element of current knee surgery practices. The goal of this study was to
      determine the effects of RI on the mechanical properties of hamstring tendons. We
      hypothesized that RI would have a detrimental effect on the mechanical properties
      of periarticular soft tissues METHODS: A tensile test to failure was performed on
      120 hamstring tendon segments harvested during ACL reconstruction surgery in 120
      patients. Two sets of tensile tests were done. The first evaluated the effect of
      RI itself on the mechanical properties of tendons: 30 samples were soaked for
      1hour in a 2% RI solution and compared to 30 samples soaked in a saline solution
      (control group). The second evaluated the effect of RI concentration on the
      mechanical properties of hamstring tendons: 30 samples were soaked for 1hour in a
      2% RI solution and 30 samples were soaked in a 7.5% RI solution. RESULTS: In the
      first test, 29 samples from each group were analyzed as two samples (one in each
      group) failed at the grip interface. The specimens exposed to 2% RI had lower
      ultimate tensile strength (Delta=4.4MPa, P=0.001), strain energy (Delta=13MPa,
      P=0.001) and Young's modulus (Delta=1.6MPa, P=0.02) than the specimens in the
      control group. There was no significant difference in the strain at failure
      between groups (Delta=5%, P=0.3). In the second test, one specimen from the 7.5%
      RI group failed during the preloading and was excluded. There was no significant
      difference in terms of the load at failure and ultimate tensile stress
      (Delta=0.45MPa, P=0.6) and strain energy (Delta=0.49MPa, P=0.49) between the two
      groups. There were significant differences in terms of elongation at failure
      (Delta=28%, P=0.0003) and Young's modulus (Delta=2.6MPa, P=0.005), with the
      specimens exposed to 7.5% RI undergoing greater deformation and having a lower
      Young's modulus. DISCUSSION: While local RI injections are widely performed in
      clinical practice, the results of this in vitro study point to short-term
      alterations of the mechanical properties of hamstring tendons. If these results
      hold in vivo, this could lead to weakness of the soft tissues exposed to this
      product, particularly the tendons and ligaments around the injection area. LEVEL
      OF EVIDENCE: Experimental study. Level 1.

PMID- 28760375
TI  - Noninvasive assessment of subclinical atherosclerosis in persons with symptoms of
      depression.
AB  - BACKGROUND AND AIMS: Depression is a mood disorder characterized by persistent
      feelings of loss of interest along with a cluster of clinical symptoms. It is a
      significant public health concern affecting 350 million people worldwide.
      Depression has an association with increased risk of cardiovascular disease. The
      World Health Organization estimates both depression and coronary artery disease
      to be the two major causes of disability-adjusted life years by year 2020. Early
      identification of subclinical cardiovascular disease in people suffering from
      depression may significantly impact risk stratification of these patients.
      METHODS: An electronic search of MEDLINE database was carried out using PubMed
      and OvidSP. Subclinical atherosclerosis was identified by coronary artery calcium
      (CAC). A total of 24 studies were identified to be included in the review.
      RESULTS: In this review of twenty-four studies, we found that twelve studies
      identified a positive association between depression and subclinical
      atherosclerosis. Ten studies found no significant association between depressive
      symptoms and coronary calcification. Whereas, two studies showed negative
      association. CONCLUSIONS: There is mixed evidence assessing the relationship
      between depression and CAC. Depressive symptoms may represent a potentially
      modifiable risk factor for early prevention of cardiovascular disease especially
      in younger patients with moderate to severe depression.

PMID- 28760376
TI  - Editorial Commentary: Deconstructing the dogma: Its time to untangle and reassess
      acute myocardial infarction care.

PMID- 28760377
TI  - The occurrence of aspiration pneumonia after emergency endotracheal intubation.
AB  - STUDY OBJECTIVE: Adverse events, including aspiration, occur during Emergency
      Department (ED) intubation, but their contemporary incidence is not well
      described. We sought to estimate the rate of aspiration pneumonia potentially
      related to emergency intubation. METHODS: We conducted a prospective
      observational study of adult patients who were endotracheally intubated in the
      ED. Using a standard definition, we determined the proportion of patients who
      developed aspiration pneumonia after intubation. Aspiration pneumonia was defined
      as any of the following in patients without a diagnosis of community acquired
      pneumonia, healthcare-associated pneumonia, or aspiration prior to intubation:
      pathogenic growth in sputum culture, unexplained hypoxemia, or radiographic
      evidence of pneumonia in the first 48h after intubation. Baseline characteristics
      and intubation details were compared for those with and without aspiration
      pneumonia. RESULTS: 879 patients were enrolled over a 30-month period. Intubation
      was facilitated by video laryngoscopy (49%), direct laryngoscopy (45%), nasal
      intubation (4%), a intubating laryngeal mask airway (1%), and a surgical airway
      (0.1%). 85% were intubated on the first attempt, 12% on the second, 3% on the
      third or more attempts. 25% of patients experienced an oxygen saturation <90%
      during the intubation. After excluding patients not eligible for the outcome
      assessment (those who died within 48h without findings of pneumonia), 66/823 (8%)
      developed aspiration pneumonia potentially related to ED intubation. In comparing
      those with and without aspiration pneumonia, there were no differences between
      first intubation attempt parameters and the occurrence of aspiration pneumonia.
      CONCLUSION: Aspiration pneumonia occurred commonly in this cohort. Although we
      did not identify any intubation factors that differed between those with and
      without with aspiration pneumonia, these findings should remind emergency
      physicians that emergency endotracheal intubation remains a high-risk procedure,
      and all care should be taken to minimize the risk of peri-intubation
      complications.

PMID- 28760378
TI  - Clinical evaluation and management of acute corrosive poisoning in adult patients
      - A ten year experience.

PMID- 28760379
TI  - Predictive factors of negative appendectomy in children.

PMID- 28760380
TI  - Trends in opioid prescribing before and after implementation of an emergency
      department opioid prescribing policy.

PMID- 28760381
TI  - Clinically significant bacteria/pyuria-the author responds.

PMID- 28760382
TI  - Identifying Knowledge Gaps in Clinicians Who Evaluate and Treat Vocal Performing
      Artists in College Health Settings.
AB  - OBJECTIVE: The goal of this study was to identify knowledge gaps in clinicians
      who evaluate and treat performing artists for illnesses and injuries that affect
      vocal function in college health settings. STUDY DESIGN: This pilot study
      utilized a web-based cross-sectional survey design incorporating common clinical
      scenarios to test knowledge of evaluation and management strategies in the vocal
      performing artist. METHODS: A web-based survey was administered to a purposive
      sample of 28 clinicians to identify the approach utilized to evaluate and treat
      vocal performing artists in college health settings, and factors that might
      affect knowledge gaps and influence referral patterns to voice specialists.
      RESULTS: Twenty-eight clinicians were surveyed, with 36% of respondents
      incorrectly identifying appropriate vocal hygiene measures, 56% of respondents
      failing to identify symptoms of vocal fold hemorrhage, 84% failing to identify
      other indications for referral to a voice specialist, 96% of respondents
      acknowledging unfamiliarity with the Voice Handicap Index and the Singers Voice
      Handicap Index, and 68% acknowledging unfamiliarity with the Reflux Symptom
      Index. CONCLUSION: The data elucidated specific knowledge gaps in college health
      providers who are responsible for evaluating and treating common illnesses that
      affect vocal function, and triaging and referring students experiencing symptoms
      of potential vocal emergencies. Future work is needed to improve the standard of
      care for this population.

PMID- 28760383
TI  - Association Between Concentrations of Hemoglobin Determined by Fecal
      Immunochemical Tests and Long-term Development of Advanced Colorectal Neoplasia.
AB  - BACKGROUND & AIMS: Colorectal cancer (CRC) screening using quantitative fecal
      immunochemical tests (FITs) is rapidly gaining ground worldwide. FITs are
      invariably used in a dichotomous manner using pre-specified cut-off values. To
      optimize FIT-based screening programs, we investigated the association between
      fecal hemoglobin (fHb) concentrations below the FIT cut-off value and later
      development of colorectal advanced neoplasia (AN). METHODS: We analyzed data
      collected from a population-based study of 9561 average-risk subjects (50-74
      years old) in the Netherlands who were offered 4 rounds of FIT screening for CRC
      from November 2006 through December 2014. We analyzed data from 7663 participants
      screened at least once and found to have a negative FIT result at baseline (below
      the cut-off value of 10 MUg Hb/ g feces). Participants were followed for a median
      of 4.7 years (interquartile range, 2.0-6.1 years); CRCs diagnosed outside the
      screening program were identified from the Dutch Comprehensive Cancer Centre
      database. Hazard ratios for AN were determined using Cox proportional hazard
      regression analyses. Logistic regression techniques were used to calculate risks
      of AN after consecutive fHb concentrations below the cut-off value. RESULTS:
      After 8 years of follow-up, participants with baseline concentrations of 8-10 MUg
      fHb/g had a higher cumulative incidence of AN (33%) than participants with 0 MUg
      fHb/g (5%) (P < .001). Multi-variate hazard ratios increased from 1.2 for
      subjects with concentrations of 0-2 MUg fHb/g to 8.2 for subjects with
      concentrations of 8-10 MUg fHb/g (P < .001). Participants with 2 consecutive fHb
      concentrations of 8 MUg Hb/g had a 14-fold increase in risk of AN compared with
      participants with 2 consecutive fHb concentrations of 0 MUg Hb/g (P < .001).
      CONCLUSIONS: In a population-based study of average-risk individuals with a FIT
      result below the cut-off value, we associated baseline concentrations of 8-10 MUg
      fHb/g with an increased risk of AN compared with baseline concentrations of 0 MUg
      fHb/g. Baseline and consecutive fHb concentrations are independent predictors for
      incident AN. This information might be used in designing personalized strategies
      for population-based CRC screening and reduce unnecessary repeat tests.
      Trialregister.nl no: first round, NTR1096; second round and additional invitees,
      NTR1512.

PMID- 28760385
TI  - Platelet factor XI: intracellular localization and mRNA splicing following
      platelet activation.
AB  - BACKGROUND: The structure and function of platelet factor XI (FXI) protein and
      the presence of F11 mRNA in platelets are controversial. Although platelets are
      anucleated cells they contain spliceosome components and pre-mRNAs. Three
      platelet proteins have been demonstrated to be spliced upon platelet activation.
      OBJECTIVE: To determine whether FXI is also spliced upon activation and to
      discern the localization of FXI in platelets. METHODS: Localization of FXI in
      platelets was assessed by confocal immunofluorescence staining. ELISA,
      chromogenic assay and western blot analyses were used to measure antigen levels,
      activity levels and size of FXI in platelets, respectively. Splicing patterns of
      F11 mRNA were assessed in three states of platelet activation: activated
      platelets, resting platelets and alphaIIbbeta3-integrin activated platelets.
      RESULTS: Platelet FXI was exhibited in platelet granules. Activated platelets
      exhibited higher levels of mature F11 mRNA and protein and lower levels of F11
      pre-mRNA compared to resting or alphaIIbbeta3-integrin activated platelets.
      CONCLUSIONS: We confirmed the presence of FXI in platelets and showed that it is
      localized in granules but is not restricted to the same alpha-granule subtype as
      von-Willebrand factor and p-selectin. Our study also shows that F11 is present in
      platelets as pre-mRNA and is spliced upon platelet activation.

PMID- 28760384
TI  - Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A
      Randomized, Placebo-Controlled Study.
AB  - BACKGROUND & AIMS: Gastroparesis is a complication of diabetes with few treatment
      options. Relamorelin (also referred to as RM-131) is a selective, prokinetic
      agonist of ghrelin. We aimed to evaluate the efficacy of relamorelin on symptoms
      and gastric emptying (GE) in a 12-week, phase 2B study of diabetic patients with
      moderate to severe gastroparesis symptoms (DG). METHODS: We performed a study of
      393 patients with DG (37.7% male; 9.9% with type 1 diabetes; median age, 58.2
      years [range 20-76]; median body mass index, 31.4 kg/m2 [range, 18.2-60.1]; HbA1c
      level, 7.6%, [range, 5.2-11.0]). All participants had 13C-spirulina GE breath
      test T1/2 values of 79 minutes or more (with 89.8% delayed relative to 90th %ile
      of normal, 85.75 minutes), recent vomiting, and gastroparesis cardinal symptom
      index-daily diary scores of 2.6 or more. Patients were randomly assigned to
      groups given placebo (n=104) or relamorelin (10 MUg [n=98], 30 MUg [n=109], or
      100 MUg [n=82] twice daily) for 12 weeks, following a 2-week, single-blind,
      placebo run-in period. Patient-reported outcomes were determined from DG Symptom
      Severity daily e-diaries, in which patients recorded vomiting frequency and
      symptom scores (nausea, abdominal pain, postprandial fullness, and bloating) on a
      0-10 scale. Endpoints were change from baseline in vomiting frequency, composite
      DG Symptom Severity score, GE, and safety. We performed longitudinal, mixed
      effects model analysis using repeated measures, with baseline and baseline-by
      week interaction values as covariates. RESULTS: Patients given relamorelin had a
      75% reduction in vomiting frequency compared with baseline, but this difference
      was not significant compared with the placebo group. All 4 symptoms of DG
      (composite or individual symptoms) were significantly reduced over the 12-week
      study period in all 3 relamorelin dose groups compared with the placebo group
      (all P < .05, based on longitudinal analysis over 12 weeks). Relamorelin
      significantly accelerated GE from baseline compared with placebo (by 12%, P < .05
      for the 10 MUg and 30 MUg groups; P = .051 for the 100 MUg group). Dose-related
      worsening of glycemic control was noted in 14.5% of patients who received
      relamorelin; some required insulin or other diabetes drug dosage adjustments.
      CONCLUSIONS: In a phase 2B randomized trial of patients with moderate to severe
      DG, relamorelin significantly reduced core symptoms of DG and overall composite
      score compared with placebo, accelerated GE, and was generally safe and well
      tolerated. ClinicalTrials.gov Identifier: NCT02357420.

PMID- 28760386
TI  - Letter from original author re. Does telomerase activity have an effect on
      infertility in patients with endometriosis? Methodological issues.

PMID- 28760387
TI  - The role of Th17 cells in auto-inflammatory neurological disorders.
AB  - The role of T helper 17 (Th17) cells in auto-inflammatory neurological disorders
      such as Multiple Sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease
      (PD) and schizophrenia has not been clarified completely. Th17-derived pro
      inflammatory cytokines including IL-17, IL-21, IL-22, IL-23, GM-CSF, and IFN
      gamma have a critical role in the pathogenesis of these disorders. In this
      review, we demonstrate the role of Th17 cells and their related cytokines in the
      immunopathology of above-mentioned disorders to get a better understanding of
      neuroinflammatory mechanisms mediated by Th17 cells associated with events
      leading to neurodegeneration.

PMID- 28760388
TI  - Baseline evaluation for natural radioactivity level and radiological hazardous
      parameters associated with processing of high grade monazite.
AB  - Egyptian monazite is a promising resource and investment attractive for
      production of valuable metals of industrial or nuclear interest such as rare
      earth elements (REEs), thorium (Th) and uranium (U). The study was focused to
      establish a baseline framework in viewpoint of radiation protection for the
      workers in production of REEs from high-grade monazite treated by sodium
      hydroxide (NaOH) solutions. Radiological hazard indices (cancer, gonadal and
      other risks) were evaluated, due to emissions (alpha-, beta- and gamma
      radiations) of radium-isotopes (228Ra, 226Ra, 223Ra) and lead (210Pb). The values
      of the estimated radiological hazard indices were higher than the permissible
      safe limits, worldwide average and varied with those reported in other countries.
      It was found that more than 70% of radioactivity and radiological hazardous
      indices resulted from emissions of 228Ra, while the rest was attributed to 226Ra,
      223Ra and 210Pb. Therefore, processing of the Egyptian monazite can cause a
      significant radiological impact on workers through external exposure from gamma
      radiations and/or internal exposure through inhalation or ingestion airborne
      contaminated by the radionuclides. Thus, the results recommended that protection
      rules could be considered to prevent the radiation hazards associated with the
      production of the REEs from the high grade monazite attacked by caustic method.

PMID- 28760389
TI  - Comparative effect of ochratoxin A on inflammation and oxidative stress
      parameters in gut and kidney of piglets.
AB  - Ochratoxin A (OTA) is a secondary metabolite produced by fungi of Aspergillus and
      Penicillium genra. OTA is mainly nephrotoxic but can also cause hepatotoxicity,
      mutagenicity, teratogenicity, neurotoxicity and immunotoxicity. As recent studies
      have highlighted the close relationship between gastrointestinal tract and
      kidney, as principal organs involved in absorption and respective excretion of
      xenobiotics, the aim of the present study was to analyze the effect of a
      subchronic exposure (30 days) to 0.05 mg/kg OTA on immune response and oxidative
      stress parameters at the level of intestine and kidney of young swine. The
      experiment was realised on twelve crossbred weaned piglets randomly allotted to
      both control group or toxin group fed 0.050 mg OTA/kg feed. Our results have
      shown that a subchronic intoxication with a low dose of OTA for 30 days affected
      the immune response and the anti-oxidant self-defense at gut and kidney level.
      The gene expression of both markers of signaling pathways involved in
      inflammation and inflammatory cytokines were affected in a much higher extent in
      the gut than in the kidney Of OTA intoxicated piglets.

PMID- 28760390
TI  - Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes
      and nicotine gum in Japanese smokers.
AB  - Two open-label randomized cross-over studies in Japanese smokers investigated the
      single-use nicotine pharmacokinetic profile of the Tobacco Heating System (THS)
      2.2, cigarettes (CC) and nicotine replacement therapy (Gum). In each study, one
      on the regular and one on the menthol variants of the THS and CC, both using Gum
      as reference, 62 subjects were randomized to four sequences: Sequence 1: THS - CC
      (n = 22); Sequence 2: CC - THS (n = 22); Sequence 3: THS - Gum (n = 9); Sequence
      4: Gum - THS (n = 9). Plasma nicotine concentrations were measured in 16 blood
      samples collected over 24 h after single use. Maximal nicotine concentration
      (Cmax) and area under the curve from start of product use to time of last
      quantifiable concentration (AUC0-last) were similar between THS and CC in both
      studies, with ratios varying from 88 to 104% for Cmax and from 96 to 98% for AUC0
      last. Urge-to-smoke total scores were comparable between THS and CC. The THS
      nicotine pharmacokinetic profile was close to CC, with similar levels of urge-to
      smoke. This suggests that THS can satisfy smokers and be a viable alternative to
      cigarettes for adult smokers who want to continue using tobacco.

PMID- 28760391
TI  - The counter-balance between ammonia absorption and the stimulation of
      volatilization by periphyton in shallow aquatic systems.
AB  - Ammonia (NH3) volatilization is one of the main pathways of nitrogen (N). The aim
      of this work was to investigate the determinants of NH3 volatilization, and
      characterize how the overlying water, sediment, and periphyton interact to
      regulate the rates of NH3 volatilization in shallow aquatic systems. Two types of
      structural equation modeling (SEM) methods ('elements' and 'components' models)
      were evaluated to examine the complex multivariate response of NH3
      volatilization. The N components and the pH in the 'elements' models exerted
      significant and positive effects on NH3 volatilization. The water column
      accounted for the greatest variation of NH3 volatilization in a favorable pH
      environment and high NH4+-N concentrations according to the 'components' models.
      Although periphyton biofilm prohibited the direct flow of NH3 gas, this was
      counter-balanced by its indirect stimulation effects that positively affected the
      NH4+-N and DOC concentrations and the pH in both the overlying water and the
      sediment.

PMID- 28760393
TI  - Sculpting epithelia with planar polarized actomyosin networks: Principles from
      Drosophila.
AB  - Drosophila research has revealed how planar polarized actomyosin networks affect
      various types of tissue morphogenesis. The networks are positioned by both tissue
      wide patterning factors (including Even-skipped, Runt, Engrailed, Invected,
      Hedgehog, Notch, Wingless, Epidermal Growth Factor, Jun N-terminal kinase, Sex
      combs reduced and Fork head) and local receptor complexes (including Echinoid,
      Crumbs and Toll receptors). Networks with differing super-structure and
      contractile output have been discovered. Their contractility can affect
      individual cells or can be coordinated across groups of cells, and such
      contractility can drive or resist physical change. For what seem to be simple
      tissue changes, multiple types of actomyosin networks can contribute, acting
      together as contractile elements or braces within the developing structure. This
      review discusses the positioning and effects of planar polarized actomyosin
      networks for a number of developmental events in Drosophila, including germband
      extension, dorsal closure, head involution, tracheal pit formation, salivary
      gland development, imaginal disc boundary formation, and tissue rotation of the
      male genitalia and the egg chamber.

PMID- 28760392
TI  - Fractal properties of cell surface structures: A view from AFM.
AB  - Cell surfaces are densely populated with various proteins. Aggregation of these
      proteins to nanoscale clusters can be critical for various cellular functions
      such as signaling, motility and division. Quantitative characterization of
      corresponding structures and their changes might be useful to understand these
      basic cell processes and serve as an early marker of cellular stress or diseases.
      Atomic force microscopy (AFM) allows high-resolution imaging of cell surface
      structures, resolving fine details of these structures. Moreover, AFM enables
      simultaneous imaging of cell surface morphology and mapping of its' mechanical
      characteristics. This review focuses on applying the fractal dimension measure as
      a sensitive method to quantify single cell surface structures and their changes
      from AFM images.

PMID- 28760394
TI  - Molecular structure of FoxE, the putative iron oxidase of Rhodobacter
      ferrooxidans SW2.
AB  - The ancient metabolism of photoferrotrophy is likely to have played a key role in
      the biogeochemical cycle of iron on Early Earth leading to the deposition of
      Banded Iron Formations prior to the emergence of oxygenic photosynthesis. Extant
      organisms still performing this metabolism provide a convenient window to peer
      into its molecular mechanisms. Here we report the molecular structure of FoxE,
      the putative terminal iron oxidase of Rhodobacter ferrooxidans SW2. This protein
      is organized as a trimer with two hemes and a disulfide bridge per monomer. The
      distance between hemes, their solvent exposure and the surface electrostatics
      ensure a controlled electron transfer rate. They also guarantee segregation
      between electron capture from ferrous iron and electron release to downstream
      acceptors, which do not favor the precipitation of ferric iron. Combined with the
      functional characterization of this protein, the structure reveals how iron
      oxidation can be performed in the periplasmic space of this Gram-negative
      bacterium at circumneutral pH, while minimizing the risk of mineral precipitation
      and cell encrustation.

PMID- 28760395
TI  - Institutional experience and outcomes of transcatheter aortic valve replacement:
      Results from an international multicentre registry.
AB  - BACKGROUND: Despite rapidly increasing use of TAVR across institutions, limited
      data is available for the effect of procedural experience on TAVR outcomes. We
      investigate the relationship between institutional experience and TAVR outcomes.
      METHODS: 1953 patients undergoing TAVR at 8 international sites were grouped into
      chronological quantiles (Q) to assess temporal changes on procedural and clinical
      outcomes and multivariate logistic regression performed to determine predictors
      of device success, early safety and all-cause mortality. RESULTS: The mean age of
      patients was 81+/-7years and 991 (51%) were female. The quantiles comprised of
      first 62 cases for Q1, 63-133 for Q2, 134 to 242 for Q3 and 243 to 476 for Q4.
      Device success increased from Q1 to Q4 (78% vs 89%, p<0.001) with significant
      improvement in the early safety endpoint (19% vs 10%, p<0.001). All cause
      mortality reduced by half in Q4 compared to Q1 (8% vs 4%, p=0.01) and rates of
      major vascular complications, major bleeding and valve embolization decreased
      with increasing experience. The multivariate analysis identified TAVR in Q3 and
      Q4 to be independently associated with higher device success and lower risk of
      complications. TAVR in Q4 was independently associated with lower mortality (OR
      0.36 95% CI 0.19-0.70, p=0.002). CONCLUSIONS: Greater institutional experience
      with TAVR procedures improves device success and clinical outcomes. An experience
      of >242 cases is independently associated with lower mortality. These findings
      have important implications for defining minimum volume criteria for institutions
      and training standards for TAVR procedure.

PMID- 28760396
TI  - Transcatheter aortic valve replacement with new-generation devices: A systematic
      review and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to conduct a weighted meta-analysis to
      determine the rates of acute (<=30days) major outcomes after (TAVR) with second
      generation devices. METHODS: A comprehensive search of multiple electronic
      databases from January 2011 to May 2017 was conducted using predefined criteria.
      New-generation TAVR devices were defined as any device which received CE mark
      approval or is still under evaluation for CE marking after CoreValve and SAPIEN
      XT prostheses. RESULTS: A total of 37 studies including 10,822 patients met
      inclusion criteria and were included in the analysis. Devices investigated in the
      studies were the following: SAPIEN 3 (n=5423, 45.9%), Lotus Valve (n=3007, %),
      Portico (n=130, 1.1%), JenaValve (n=345, 2.9%), Symetis Acurate (n=1314, 11,1%),
      and Evolut R (n=1603, 13.6%). Thirty-day all-cause and cardiovascular 30-day
      death were 2.2% (95% CI: 1.6% to 2.8%) and 1.6% (95% CI: 0.9% to 2.3%),
      respectively; Any stroke and major/disabling stroke occurred at a pooled estimate
      rate of 2.6% (95% CI: 2.0% to 3.3%) and 0.9% (95% CI: 0.2% to 1.6%),
      respectively; life-threatening bleeding, 3.9% (95% CI: 2.9% to 5.0%); major
      vascular complications, 4.5% (95% CI: 3.7% to 5.4%); pacemaker implantation,
      16.2% (95% CI: 12.7% to 19.6%); more than mild aortic regurgitation, 1.6% (95%
      CI: 0.9 to 2.3). CONCLUSIONS: Second-generation TAVR devices are associated with
      very low mortality and major complications rates at 30-day, and improved
      prosthesis performance with <2% of patients having more than mild post-procedural
      aortic regurgitation. On the other hand, the need for pacemaker implantation
      seems to remain an unresolved issue, and warrants further investigation.

PMID- 28760397
TI  - Three-Dimensional Technology to Diagnose Unilateral Cervical Atresia in
      Obstructive Hemivagina with Ipsilateral Renal Anomaly: A Case Report and Review
      of the Literature.
AB  - BACKGROUND: Congenital atresia of the cervix in the setting of an obstructed
      hemivagina with ipsilateral renal anomaly (OHVIRA) is an unusual occurrence that
      is frequently missed using preoperative imaging modalities. CASE: A 14-year-old
      female adolescent presented to a tertiary care facility with abdominal pain
      associated with a mass. Initial imaging with ultrasound and magnetic resonance
      suggested OHVIRA but 3-D magnetic resonance imaging (MRI) also correctly
      identified unilateral cervical atresia on the obstructed left side. SUMMARY AND
      CONCLUSION: Three-dimensional MRI in the setting of OHVIRA was used successfully
      in this case to preoperatively identify cervical atresia and to guide
      preoperative surgical counseling and planning. The use of 3-D MRI for this
      purpose has, to our knowledge, never been described in the literature. Three
      dimensional printed models derived from 3-D MRI can play an evolving role in the
      management of Mullerian anomalies as preoperative planning and surgical
      counseling tools.

PMID- 28760400
TI  - New perspectives for TAS-102: TASK successful?

PMID- 28760398
TI  - Symptomatic Clitoromegaly: Case Report of a Clitoral Hemangioma.
AB  - BACKGROUND: Clitoromegaly is often a sign of an underlying disorder of sexual
      development. Isolated clitoromegaly might occur as a result of benign or
      malignant neoplasm. CASE: A 10-year-old girl presented with clitoral swelling and
      discomfort and was noted to have a 5 * 2 * 2 cm, tender, cystic mass in the left
      periclitoral area. Ultrasound confirmed the primarily cystic nature of the
      lesion. At surgery the mass was carefully excised not damaging the clitoral
      neurovascular bundle. Pathology showed a hemangioma. SUMMARY AND CONCLUSION:
      Differentiating between potential etiologies of clitoromegaly requires a careful
      history, physical examination, select hormone levels determination, imaging, and
      pathology, which allows for appropriate management. In this case the pain,
      tenderness, disfigurement, and imaging showing a cystic mass resulted in surgical
      removal of the mass.

PMID- 28760401
TI  - Correction to Lancet Oncol 2016; 17: 727-37.

PMID- 28760399
TI  - TAS-102 plus bevacizumab for patients with metastatic colorectal cancer
      refractory to standard therapies (C-TASK FORCE): an investigator-initiated, open
      label, single-arm, multicentre, phase 1/2 study.
AB  - BACKGROUND: In patients with heavily treated metastatic colorectal cancer, TAS
      102-a combination of trifluridine and tipiracil-has shown a significant overall
      survival benefit compared with placebo. In preclinical models, TAS-102 plus
      bevacizumab has shown enhanced activity against colorectal cancer xenografts
      compared with that for either drug alone. In this phase 1/2 study, we assessed
      the activity and safety of TAS-102 plus bevacizumab. METHODS: We did this
      investigator-initiated, open-label, single-arm, multicentre, phase 1/2 trial of
      TAS-102 plus bevacizumab in four cancer centres in Japan. Eligible patients were
      aged 20 years or older; had histologically confirmed unresectable, metastatic
      colorectal adenocarcinoma; were refractory or intolerant to fluoropyrimidine,
      irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumours
      with wild-type KRAS); and had no previous treatment with regorafenib. Patients
      had to have an Eastern Cooperative Oncology Group performance status of 0 or 1.
      Using a dose de-escalation design in phase 1, the recommended phase 2 dose (RP2D)
      was determined for TAS-102 (35 mg/m2 given orally twice daily on days 1-5 and 8
      12 in a 28-day cycle for level 1) plus bevacizumab (5 mg/kg, administered by
      intravenous infusion for 30 min every 2 weeks). In phase 2, patients received the
      RP2D. The primary endpoint was centrally assessed progression-free survival at 16
      weeks, analysed in the first 21 patients to be enrolled and treated with the RP2D
      who had at least one imaging assessment. This study is completed and registered
      with the University Hospital Medical Information Network, number UMIN000012883.
      FINDINGS: Between Feb 25, 2014, and July 23, 2014, we enrolled 25 patients with
      metastatic colorectal cancer: six patients in phase 1 and 19 patients in phase 2.
      The six patients who received TAS-102 at level 1 experienced no dose-limiting
      toxicities and this was deemed the RP2D. Nine of 21 patients who received the
      RP2D did not have a centrally assessed progression event; 16-week progression
      free survival was 42.9% (80% CI 27.8-59.0). The most common grade 3 or worse
      adverse events as assessed in all 25 patients were neutropenia (18 [72%]
      patients), leucopenia (11 [44%]), anaemia (four [16%]), febrile neutropenia (four
      [16%]), and thrombocytopenia (three [12%]). Treatment-related serious adverse
      events were reported in three (12%) patients. No treatment-related deaths
      occurred. INTERPRETATION: TAS-102 plus bevacizumab has promising activity with
      manageable safety, suggesting that this combination might become a potential
      treatment option for patients with metastatic colorectal cancer in a refractory
      setting. FUNDING: Taiho Pharmaceutical.

PMID- 28760402
TI  - Androgen deprivation in prostate cancer: first do no harm.

PMID- 28760404
TI  - Retinal toxicity after accidental intravitreal injection of mepivacaine and
      adrenaline.
AB  - CASE REPORT: The case is presented of a 32 year-old male with no medical history
      of interest who suffered a traffic accident with mild traumatic brain injury. He
      had a left supraciliary incised and contused wound that extended to the left
      upper eyelid, with no loss of vision. After palpebral anaesthetic injection,
      there was a sudden visual acuity decrease in the left eye and hyposphagma located
      between I-III at 4mm from the limbus, with increased intraocular pressure. A
      whitish lesion with a central haemorrhagic focus was observed in the ocular
      fundus, corresponding to the area where the hyposphagma was located. DISCUSSION:
      Anaesthetic injection during palpebral repair may be complicated by inadvertent
      penetration of the eyeball. Intravitreal mepivacaine and adrenaline could cause
      macular and retinal lesions.

PMID- 28760403
TI  - Health-related quality of life for immediate versus delayed androgen-deprivation
      therapy in patients with asymptomatic, non-curable prostate cancer (TROG 03.06
      and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial.
AB  - BACKGROUND: Androgen-deprivation therapy in patients with prostate cancer who
      have relapsed with rising prostate-specific antigen concentration only (PSA-only
      relapse), or with non-curable but asymptomatic disease at diagnosis, could
      adversely affect quality of life at a time when the disease itself does not. We
      aimed to compare the effect of immediate versus delayed androgen-deprivation
      therapy on health-related quality of life over 5 years in men enrolled in the
      TOAD (Timing of Androgen Deprivation) trial. METHODS: This randomised,
      multicentre, open-label, phase 3 trial done in 29 public and private cancer
      centres across Australia, New Zealand, and Canada compared immediate with delayed
      androgen-deprivation therapy in men with PSA-only relapse after definitive
      treatment, or de-novo non-curable disease. Patients were randomly assigned (1:1)
      with a database-embedded, dynamically balanced algorithm to immediate androgen
      deprivation therapy (immediate therapy group) or to delayed androgen-deprivation
      therapy (delayed therapy group). Any type of androgen-deprivation therapy was
      permitted, as were intermittent or continuous schedules. The European
      Organisation for Research and Treatment of Cancer (EORTC) quality-of-life
      questionnaires QLQ-C30 and PR25 were completed before randomisation, every 6
      months for 2 years, and annually for a further 3 years. The primary outcome of
      the trial, reported previously, was overall survival, with global health-related
      quality of life at 2 years as a secondary endpoint. Here we report prespecified
      secondary objectives of the quality-of-life endpoint. Analysis was by intention
      to treat. Statistical significance was set at p=0.0036. The trial was registered
      with the Australian New Zealand Clinical Trials Registry, number
      ACTRN12606000301561, and ClinicalTrials.gov, number NCT00110162. FINDINGS:
      Between Sept 3, 2004, and July 13, 2012, 293 men were recruited and randomly
      assigned; 151 to the delayed therapy group and 142 to the immediate therapy
      group. There was no difference between the two groups in global health-related
      quality of life over 2 years from randomisation. There were no statistically
      significant differences in global quality of life, physical functioning, role
      functioning, or emotional functioning, fatigue, dyspnoea, insomnia, or feeling
      less masculine over the entire 5 years after randomisation. Sexual activity was
      lower in the immediate therapy group than in the delayed group at 6 and 12 months
      (at 6 months mean score 29.20 [95% CI 24.59-33.80] in the delayed group vs 10.40
      [6.87-13.93] in the immediate group, difference 18.80 [95% CI 13.00-24.59],
      p<0.0001; at 12 months 28.63 [24.07-33.18] vs 13.76 [9.94-17.59], 14.86 [8.95
      20.78], p<0.0001), with the differences exceeding the clinically significant
      threshold of 10 points until beyond 2 years. The immediate therapy group also had
      more hormone-treatment-related symptoms at 6 and 12 months (at 6 months mean
      score 8.48 [95% CI 6.89-10.07] in the delayed group vs 15.97 [13.92-18.02] in the
      immediate group, difference -7.49 [-10.06 to -4.93], p<0.0001; at 12 months 9.32
      [7.59-11.05] vs 17.07 [14.75-19.39], -7.75 [-10.62 to -4.89], p<0.0001), but with
      differences below the threshold of clinical significance. For the individual
      symptoms, hot flushes were clinically significantly higher in the immediate group
      (adjusted proportion 0.31 for delayed therapy vs 0.55 for immediate therapy,
      adjusted odds ratio 2.87 [1.96-4.21], p<0.0001) over the 5-year period, as were
      nipple or breast symptoms (0.06 vs 0.14, 2.64 [1.61-4.34], p=0.00013).
      INTERPRETATION: Immediate use of androgen-deprivation therapy was associated with
      early detriments in specific hormone-treatment-related symptoms, but with no
      other demonstrable effect on overall functioning or health-related quality of
      life. This evidence can be used to help decision making about treatment
      initiation for men at this disease stage. FUNDING: Australian National Health and
      Medical Research Council and Cancer Councils, The Royal Australian and New
      Zealand College of Radiologists, Mayne Pharma Australia, Tolmar Australia.

PMID- 28760405
TI  - Purtscher-like retinopathy preceding acute renal failure.
AB  - CASE REPORT: The case is reported of a 61 year-old woman with Purtscher-like
      retinopathy associated with acute renal failure. Ophthalmic examination,
      fluorescein-angiography, and optical coherence tomography were consistent with
      Purtscher-like retinopathy. Ophthalmic symptoms and signs preceded renal failure.
      Pancreatitis and other systemic diseases were ruled out. The patient developed a
      neovascular glaucoma. DISCUSSION: Purtscher-like retinopathy rarely precedes the
      associated systemic illness. Early diagnosis based on ophthalmic symptoms may
      help in the recognition and treatment of the disease, and prevent later
      complications.

PMID- 28760406
TI  - The variation in frequency locations in Doppler ultrasound spectra for maximum
      blood flow velocities in narrowed vessels.
AB  - This study assessed the variation in the frequency locations in the Doppler
      ultrasound spectra for the maximum blood flow velocities of in vessels with
      different degrees of bilaterally axisymmetric stenosis. This was done by
      comparing the relationship between the velocity distributions and corresponding
      Doppler power spectra. First, a geometric vessel model with axisymmetric stenosis
      was established. This made it possible to obtain the blood flow velocity
      distributions for different degrees of stenosis from the solutions of the Navier
      Stokes equations. Then, the Doppler spectra were calculated for the entire
      segment of the vessel that was covered by the sound field. Finally, the maximum
      frequency locations for the spectra were determined based on the intersections of
      the maximum values chosen from the calculated blood flow velocity distributions
      and their corresponding spectra. The computational analysis showed that the
      maximum frequencies, which corresponded to the maximum blood flow velocities for
      different degrees of stenosis, were located at different positions along the
      spectral falling edges. The location for a normal (stenosis free) vessel was in
      the middle of the falling edge. For vessels with increasing degrees of stenosis,
      this location shifted approximately linearly downward along the falling edge. For
      40% stenosis, the location reached a position at the falling edge of 0.32.
      Results obtained using the Field II simulation tool demonstrated the validity of
      the theoretical analysis and calculations, and may help to improve the maximum
      velocity estimation accuracy for Doppler blood flow spectra in stenosed vessels.

PMID- 28760407
TI  - Development of an acoustic measurement protocol to monitor acetabular implant
      fixation in cementless total hip Arthroplasty: A preliminary study.
AB  - In cementless total hip arthroplasty (THA), the initial stability is obtained by
      press-fitting the implant in the bone to allow osseointegration for a long term
      secondary stability. However, finding the insertion endpoint that corresponds to
      a proper initial stability is currently based on the tactile and auditory
      experiences of the orthopedic surgeon, which can be challenging. This study
      presents a novel real-time method based on acoustic signals to monitor the
      acetabular implant fixation in cementless total hip arthroplasty. Twelve acoustic
      in vitro experiments were performed on three types of bone models; a simple bone
      block model, an artificial pelvic model and a cadaveric model. A custom made beam
      was screwed onto the implant which functioned as a sound enhancer and insertor.
      At each insertion step an acoustic measurement was performed. A significant
      acoustic resonance frequency shift was observed during the insertion process for
      the different bone models; 250 Hz (35%, second bending mode) to 180 Hz (13%,
      fourth bending mode) for the artificial bone block models and 120 Hz (11%, eighth
      bending mode) for the artificial pelvis model. No significant frequency shift was
      observed during the cadaveric experiment due to a lack of implant fixation in
      this model. This novel diagnostic method shows the potential of using acoustic
      signals to monitor the implant seating during insertion.

PMID- 28760408
TI  - Relationship between serum inflammatory markers and vascular function in a cohort
      of adolescents with type 1 diabetes.
AB  - OBJECTIVE: The contribution of inflammation to endothelial/vascular dysfunction
      in early Type I Diabetes (T1D) is not well understood. The objective of this
      study was to examine the interaction between systemic inflammation and vascular
      function in adolescent's with and without-T1D. METHODS: 51 subjects from our
      observational cohort of adolescents with T1D (JDRF-CCTN), and 59 healthy controls
      (HC) were studied. Serum cytokines-chemokines were quantified using Human 41-Plex
      Array, and vascular function was measured by Flow Mediated Dilatation (FMD),
      Pulse Wave Velocity (PWV) and Blood Pressure (BP). Factor Analysis was used to
      identify pro- and anti-inflammatory cytokine-chemokine factors, which were then
      correlated with vascular outcomes. RESULTS: Three pro-inflammatory factors were
      identified in HC and three in TID, and a single anti-inflammatory factor in both
      groups. In HC there was a positive correlation (r=0.33; p=0.01) between control
      proinflammatory Factor 1 and systolic BP and a negative correlation between
      control proinflammatory Factor 3(r=-0.29; p=0.02) and diastolic BP. Control
      proinflammatory Factor 2 correlated positively with PWV. In TID subjects, no
      correlations were found between any of the pro-inflammatory factors and the
      vascular measurements. No correlations were found between the anti-inflammatory
      factors and BP, FMD and PWV in either HC or T1D. Levels of pro-inflammatory
      analytes, EGF, GRO, PDGF-BB, PDGF-AA and sCD40L were significantly higher in T1D.
      CONCLUSIONS: The cytokine-chemokine signature in early T1D, prior to the
      development of arterial disease, is significantly different from that seen in
      healthy controls. This may be relevant to pathophysiology, determining risk and
      identifying target cytokines-chemokines for intervention in T1D.

PMID- 28760410
TI  - The Impact of Rehabilitation Frequencies in the First Year after Stroke on the
      Risk of Recurrent Stroke and Mortality.
AB  - BACKGROUND: Rehabilitation is essential for all poststroke patients to improve
      self-care ability. However, whether an increased frequency of rehabilitation
      reduces poststroke adverse events remains undetermined. METHODS: We recruited
      4899 patients with newly diagnosed ischemic stroke between January 1, 2000, and
      December 31, 2008, from our database and divided them into 3 groups according to
      their Charlson Comorbidity Index, and they were further categorized into 3 groups
      of different rehabilitation frequencies during their first year after stroke.
      Clinical adverse events including recurrent stroke, hip fracture, pneumonia, and
      all-cause mortality were analyzed by Cox regression analysis to investigate the
      protective effects of aggressive rehabilitation. RESULTS: We discovered that
      aggressive rehabilitation in the first year after stroke was significantly
      associated with a lower incidence of recurrent stroke and all-cause mortality
      despite the severity of patients' comorbidities. Further Cox regression analysis
      revealed decreased hazard ratios to develop recurrent stroke and all-cause
      mortality in patients with more intensive rehabilitation (P for trend <.05).
      However, no significant associations between rehabilitation frequency and
      pneumonia and hip fracture were identified in our study. CONCLUSION: Intensive
      rehabilitation during the first year after stroke should be recommended to
      prevent detrimental adverse events for stroke survivors.

PMID- 28760409
TI  - Development and Reliability of a User-Friendly Multicenter Phenotyping
      Application for Hemorrhagic and Ischemic Stroke.
AB  - BACKGROUND: Annotation and Image Markup on ClearCanvas Enriched Stroke
      phenotyping Software (ACCESS) is a novel stand-alone computer software
      application that allows the creation of simple standardized annotations for
      reporting brain images of all stroke types. We developed the ACCESS application
      and determined its inter-rater and intra-rater reliability in the Stroke
      Investigative Research and Educational Network (SIREN) study to assess its
      suitability for multicenter studies. METHODS: One hundred randomly selected
      stroke imaging reports from 5 SIREN sites were re-evaluated by 4 trained
      independent raters to determine the inter-rater reliability of the ACCESS
      (version 12.0) software for stroke phenotyping. To determine intra-rater
      reliability, 6 raters reviewed the same cases previously reported by them after a
      month of interval. Ischemic stroke was classified using the Oxfordshire Community
      Stroke Project (OCSP), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and
      Atherosclerosis, Small-vessel disease, Cardiac source, Other cause (ASCO)
      protocols, while hemorrhagic stroke was classified using the Structural lesion,
      Medication, Amyloid angiopathy, Systemic disease, Hypertensive angiopathy and
      Undetermined (SMASH-U) protocol in ACCESS. Agreement among raters was measured
      with Cohen's kappa statistics. RESULTS: For primary stroke type, inter-rater
      agreement was .98 (95% confidence interval [CI], .94-1.00), while intra-rater
      agreement was 1.00 (95% CI, 1.00). For OCSP subtypes, inter-rater agreement was
      .97 (95% CI, .92-1.00) for the partial anterior circulation infarcts, .92 (95%
      CI, .76-1.00) for the total anterior circulation infarcts, and excellent for both
      lacunar infarcts and posterior circulation infarcts. Intra-rater agreement was
      .97 (.90-1.00), while inter-rater agreement was .93 (95% CI, .84-1.00) for TOAST
      subtypes. Inter-rater agreement ranged between .78 (cardioembolic) and .91 (large
      artery atherosclerotic) for ASCO subtypes and was .80 (95% CI, .56-1.00) for
      SMASH-U subtypes. CONCLUSION: The ACCESS application facilitates a concordant and
      reproducible classification of stroke subtypes by multiple investigators, making
      it suitable for clinical use and multicenter research.

PMID- 28760412
TI  - Interfacial tension of reactive, liquid interfaces and its consequences.
AB  - Dispersions of immiscible liquids, such as emulsions and polymer blends, are at
      the core of many industrial applications which makes the understanding of their
      properties (morphology, stability, etc.) of great interest. A wide range of these
      properties depend on interfacial phenomena, whose understanding is therefore of
      particular importance. The behaviour of interfacial tension in emulsions and
      polymer blends is well-understood - both theoretically and experimentally - in
      the case of non-reactive stabilization processes using pre-made surfactants.
      However, this description of the interfacial tension behaviour in reactive
      systems, where the stabilizing agents are created in-situ (and which is more
      efficient as a stabilization route for many systems), does not yet find a
      consensus among the community. In this review, we compare the different theories
      which have been developed for non-reactive and for reactive systems, and we
      discuss their ability to capture the behaviour found experimentally. Finally, we
      address the consequences of the reactive stabilization process both on the global
      emulsions or polymer blend morphologies and at the interfacial scale.

PMID- 28760411
TI  - Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke:
      Meta-Analysis.
AB  - INTRODUCTION: The association between ischemic stroke and genetic polymorphisms
      of methylenetetrahydrofolate reductase (MTHFR; 677C>T and 1298A>C), endothelial
      nitric oxide synthase (eNOS; -786T>C, +894G>T, and variable number tandem repeat
      [VNTR]), phosphodiesterase 4D (PDE4D; SNPs 83 and 87), angiotensin-converting
      enzyme (ACE) I/D, angiotensinogen (AGT) 235M>T, paraoxonase 1 (PON1) 192Q>R, and
      apolipoprotein E (ApoE) epsilon2epsilon3epsilon4 remains inconclusive. Therefore,
      this updated meta-analysis aimed to clarify the presumed influence of genetic
      polymorphisms on ischemic stroke by meta-analyzing the comprehensive coverage of
      all individual association studies. METHODS: All case-control studies published
      in different languages such as English, Japanese, Korean, Spanish, Chinese,
      Hungarian, Ukrainian, or Russian were identified from databases. The pooled odds
      ratios (ORs) and 95% confidence intervals (CIs) were calculated via fixed- and
      random-effect models. Sensitivity analysis, heterogeneity test, Hardy Weinberg
      Equilibrium, and Egger's regression analyses were performed in this study.
      RESULTS: A total of 490 case-control studies with 138,592 cases and 159,314
      controls were included in this meta-analysis. Pooled ORs from all the genetic
      models indicated that MTHFR 677TT and 1298CC, eNOS +894TT and VNTR, PDE4D SNP 83,
      ACE DD, AGT 235TT, PON1 192RR, and ApoE epsilon4 polymorphisms were increasing
      the risks of ischemic stroke. Nevertheless, PDE4D SNP 87 and eNOS -786T>C
      polymorphisms are not associated with ischemic stroke risks. CONCLUSIONS: Hence,
      the evidence from this meta-analysis concluded that MTHFR (677C>T and 1298A>C),
      eNOS (+894G>T and VNTR), PDE4D SNP 83, ACE I/D, AGT 235M>T, PON1 192Q>R, and ApoE
      epsilon2epsilon3epsilon4 polymorphisms predispose individuals to ischemic stroke.

PMID- 28760413
TI  - Circulating levels of hydrogen sulfide and substance P in patients with sepsis.
AB  - OBJECTIVE: To determine alterations of circulating levels of hydrogen sulfide and
      substance P in patients with sepsis compared to non-sepsis patients with similar
      disease severity and organ dysfunction. METHODS: This study included 23 septic
      and 14 non-septic patients during 2015-16 study period at the Christchurch
      Hospital Intensive Care Unit, Christchurch, New Zealand. Blood samples were
      collected from the time of admission to 96 h, with collection at different time
      points (0 h, 12 h, 24 h, 48 h, 72 h and 96 h) and subjected to measurement of
      hydrogen sulfide, substance P, procalcitonin, C-reactive protein, interleukin-6
      and lactate levels. RESULTS: Patients with sepsis showed higher circulating
      hydrogen sulfide and substance P levels compared to patients without sepsis.
      Hydrogen sulfide levels were significantly higher at 12 h (1.45 vs 0.75 MUM; p <
      0.05) and 24 h (1.11 vs 0.72 MUM; p < 0.01), whereas substance P levels were
      higher at 48 h (0.55 vs 0.31 ng/mL; p < 0.05). Increased hydrogen sulfide and
      substance P levels in septic patients were associated with increased levels of
      inflammatory mediators - procalcitonin, C-reactive protein and interleukin-6.
      CONCLUSIONS: These results provide evidence that higher circulating levels of
      hydrogen sulfide and substance P are associated with increased inflammatory
      response in patients with sepsis.

PMID- 28760415
TI  - Surface Glycans: A Therapeutic Opportunity for Kinetoplastid Diseases.
AB  - Trypanosomal diseases are in need of innovative therapies that exploit novel
      mechanisms of action. The cell surface of trypanosomatid parasites is
      characterized by a dense coat of glycoconjugates with important functions in host
      cell recognition, immune evasion, infectivity, and cell function. The nature of
      parasite surface glycans is highly dynamic and changes during differentiation and
      in response to different stimuli through the action of glycosyltransferases and
      glycosidases. Here we propose a new approach to antiparasitic drug discovery that
      involves the use of carbohydrate-binding agents that bind specifically to cell
      surface glycans, giving rise to cytotoxic events and parasite death. The
      potential and limitations of this strategy are addressed with a specific focus on
      the treatment of sleeping sickness.

PMID- 28760414
TI  - First case of multidrug-resistant Enterococcus faecalis isolated from herding
      horse in Xinjiang, Western China.

PMID- 28760416
TI  - Late consequences of venous thromboembolism: Measuring quality of life after deep
      vein thrombosis and pulmonary embolism.
AB  - The identification of specific post-thrombotic complications as well as an
      increased appreciation of the importance of patient-reported outcome measures
      have triggered an interest in studying health-related quality of life (HRQoL) in
      patients with a history of venous thromboembolism (VTE). In order to enable a
      comprehensive assessment of HRQoL in clinical trials it is recommended that both
      generic and disease-specific questionnaires be used. SF-36 and EQ-5D are the most
      widely used generic questionnaires in VTE studies, whereas several disease
      specific questionnaires have been developed to evaluate HRQoL following deep vein
      thrombosis (DVT) and in chronic venous disease (CVD). The most widely used of
      these is the VEINES-QOL/Sym, which was developed for CVD. VT-QOL and DVTQOL are
      both questionnaires developed to evaluate HRQoL after DVT, while PEmb-QoL is
      currently the only available disease-specific questionnaire developed
      specifically for pulmonary embolism (PE). Although studies show inconsistent
      results, patients who sustain DVT seem in general to report similar HRQoL
      compared to the general population. However, patients who develop PTS after DVT
      report poorer HRQoL using both generic and disease-specific questionnaires. HRQoL
      appears to be impaired in patients who sustain PE compared to the general
      population. In these patients, persistent dyspnea after PE has been shown to be a
      predictor of reduced HRQoL. Further work is needed to develop practical, patient
      derived, valid, reliable and responsive disease-specific HRQoL instruments
      covering the specific aspects of these diseases.

PMID- 28760418
TI  - Energy and nutrient intake of infants and young children in pastoralist
      communities of Ethiopia.
AB  - OBJECTIVE: Nutrient intake from complementary foods often is suboptimal in
      subsistent farming households of developing countries, but little is known about
      this in pastoralist communities. The aim of this study was to estimate the energy
      and nutrient intake of children ages 6 to 23 mo living in pastoralist communities
      of Ethiopia. METHOD: As part of the Ethiopian National Food Consumption Survey,
      24-h dietary recall data were collected through in-home interviews from a
      nationally representative sample. In the present study, we report on the feeding
      characteristics, energy and nutrient intake of infants and young children (ages 6
      23 mo) living in pastoralist communities (N = 896) of Ethiopia. Energy and
      nutrient intakes were estimated and compared with estimated needs from
      complementary foods. The nutrient density of the complementary diets was compared
      with desired densities. RESULTS: About one-third of the children were stunted.
      Diets were predominantly dairy and cereal-based. The dietary diversity score was
      low (2 +/- 1.2). Consumption of nutrient-dense foods such as animal source foods
      (other than milk), vitamin A-rich fruits and vegetables was very low. Energy
      intake from complementary foods were inadequate. Multiple micronutrient
      deficiencies including thiamin, niacin, iron, zinc, and calcium and in some
      instances vitamins A and C were observed in young children. The number of
      micronutrients for which intake was found deficient increased with child's age.
      CONCLUSION: Energy and nutrient intakes from complementary foods are inadequate
      in pastoralist communities of Ethiopia. Interventions that improve knowledge and
      practice of complementary feeding are needed in this setting.

PMID- 28760417
TI  - Cellodextrin phosphorylase from Ruminiclostridium thermocellum: X-ray crystal
      structure and substrate specificity analysis.
AB  - The GH94 glycoside hydrolase cellodextrin phosphorylase (CDP, EC 2.4.1.49)
      produces cellodextrin oligomers from short beta-1->4-glucans and alpha-D-glucose
      1-phosphate. Compared to cellobiose phosphorylase (CBP), which produces
      cellobiose from glucose and alpha-D-glucose 1-phosphate, CDP is biochemically
      less well characterised. Herein, we investigate the donor and acceptor substrate
      specificity of recombinant CDP from Ruminiclostridium thermocellum and we isolate
      and characterise a glucosamine addition product to the cellobiose acceptor with
      the non-natural donor alpha-D-glucosamine 1-phosphate. In addition, we report the
      first X-ray crystal structure of CDP, along with comparison to the available
      structures from CBPs and other closely related enzymes, which contributes to
      understanding of the key structural features necessary to discriminate between
      monosaccharide (CBP) and oligosaccharide (CDP) acceptor substrates.

PMID- 28760419
TI  - Hypoglycemic and hypolipidemic effect of Vaccinium myrtillus L. leaf and
      Phaseolus vulgaris L. seed coat extracts in diabetic rats.
AB  - OBJECTIVES: The aim of this study was to examine the hypoglycemic and
      hypolipidemic effects of Vaccinium myrtillus L. leaf (VLE) and Phaseolus vulgaris
      L. seed coat (PCE) plant extracts, containing polyphenolic compounds, on
      carbohydrate and lipid metabolism in Wistar rats with streptozotocin (STZ) and
      high-fructose diet (HFD)-induced diabetes. METHODS: Male Wistar rats with STZ and
      HFD-induced diabetes were fed with or without VLE or PCE for 50 d. At different
      intervals, blood glucose and body weight were recorded. Blood samples were used
      to determine glycated hemoglobin (HbA) and parameters of lipid profile in serum.
      Additionally, the levels of serum diene conjugates and malondialdehyde were
      assessed. RESULTS: Results of HbA and blood glucose level analysis showed the
      ameliorative effect of VLE on carbohydrate metabolism in diabetic rats. Of the
      eight diabetic animals treated with bilberry leaf extract, four had normal HbA
      levels. A significant reduction was observed in VLE group in blood glucose level
      compared with control diabetic rats (level of hyperglycemia decreased to normal
      values in 50% of animals versus 0% in the control diabetic group). VLE treatment
      normalized parameters of lipid metabolism. There was no significant difference
      from the same parameters in the intact control group. Administration of PCE
      significantly (P < 0.05) decreased the levels of plasma triacylglycerol (0.81 +/-
      0.06 mmol/L) and low-density lipoprotein (0.74 +/- 0.10 mmol/L) in blood serum
      compared with the diabetic control group (1.36 +/- 0.13 and 1.85 +/- 0.30,
      respectively). Moreover, VLE and PLE showed an antioxidant effect on diene
      compounds in the blood serum of rats. A significant decrease was found in the
      plasma diene conjugate levels in PLE group (1.16 +/- 0.11 nmol/mL) compared with
      control diabetic rats (2.09 +/- 0.21 nmol/mL; P < 0.05). There was no significant
      difference from the same parameter in the VLE and intact control groups.
      CONCLUSIONS: The set of results that was obtained in the present study reveals
      lipid-lowering and antioxidant action related to the administration of VLE and
      PCE in Wistar rats with diabetes, induced by STZ, in combination with a high
      carbohydrate diet. VLE to a certain extent also reduced hyperglycemia in diabetic
      animals.

PMID- 28760420
TI  - Association between 24-h urinary sodium excretion and obesity in Korean adults: A
      multicenter study.
AB  - OBJECTIVE: The aim of this study was to explore the association between sodium
      intake, as assessed by 24-h urinary sodium excretion, and various obesity
      parameters among South Korean adults. The associations of 24-h urinary sodium
      excretion and sodium intake calculated from the dietary questionnaire with
      obesity parameters also were compared. METHODS: This multicenter, cross-sectional
      study analyzed data of 640 healthy adults from eight provinces in South Korea.
      Obesity was assessed by body mass index (BMI), waist circumference (WC), waist-to
      hip ratio (WHR), and waist-to-height ratio (WHtR). Mean 24-h urinary sodium
      excretion was calculated from repeatedly collected 24-h urine samples.
      Participants' dietary intake was assessed by 24-h dietary recall interview on the
      days before 24-h urine collection. RESULTS: In both sexes, the means of all
      anthropometric measurements tended to increase proportionally with 24-h urinary
      sodium excretion quartiles, regardless of adjustment. Men in the highest quartile
      (Q4) of 24-h urinary sodium excretion had increased odds of obesity (as assessed
      by BMI, WC, WHR, and WHtR) compared with men in the three lower quartiles (Q1-Q3)
      of 24-h urinary sodium excretion. Women in Q4 of 24-h urinary sodium excretion
      exhibited a higher chance of general obesity and abdominal obesity. Sodium intake
      calculated from the dietary questionnaire was not significantly associated with
      obesity in either sex. CONCLUSIONS: In Korean adults, there was a positive
      association between higher sodium intake as assessed by 24-h urinary sodium
      excretion and obesity independent of energy intake.

PMID- 28760421
TI  - Assessment of the nutritional status of adult patients with acute myeloid
      leukemia during induction chemotherapy.
AB  - OBJECTIVE: To the best of our knowledge, few studies have evaluated the
      nutritional status in patients with acute myeloid leukemia (AML) during induction
      treatment. The aim of this retrospective study was to describe nutritional status
      of newly diagnosed adult patients with AML at admission and during induction
      chemotherapy. METHODS: We included consecutive newly diagnosed adult patients
      with AML who were admitted to the Department of Hematology (Limoges University
      Hospital) from April 2010 to January 2014. Nutritional assessment included body
      mass index (BMI) and weight loss to diagnose undernutrition. Weekly laboratory
      tests were collected and total energy expenditure was calculated to adapt food
      intake. RESULTS: Of 95 patients, 14 (15%) presented with undernutrition at
      admission: low BMI values (P < 0.001) and weight loss >5% for 9.5% patients.
      After chemotherapy induction, 17 patients (18%) were undernutrition (P = 0.05).
      Patients without undernutrition had a significantly lower median weight, BMI, and
      serum albumin level at discharge compared with their admission values (P < 0.05);
      whereas their serum transthyretin levels were higher (P = 0.03). They also had
      shorter hospital stays than patients with undernutrition (31 versus 39 d; P =
      0.03) and longer survival at 12 mo (89.9 versus 58.3%; P = 0.002). CONCLUSIONS:
      Patients with AML with good nutritional status undergoing induction chemotherapy
      have shorter hospital stays and longer survival.

PMID- 28760422
TI  - With antitransglutaminase antibodies in the breast milk, is breastfeeding
      beneficial or harmful?
AB  - Breast milk is fundamental to induce an appropriate immunotolerance in the
      newborn. Here, we present the case of a young mother who was diagnosed with
      celiac disease while breastfeeding. She is dealing with the problem of knowing
      that celiac disease-specific autoantibodies are present in her breast milk, but
      not knowing if they are potentially harmful to her baby.

PMID- 28760423
TI  - Hunger and satiety responses to high-fat meals after a high-polyunsaturated fat
      diet: A randomized trial.
AB  - OBJECTIVE: Previous studies have shown that polyunsaturated fats (PUFAs) elicit a
      greater response in satiety after a single-meal challenge compared with other
      types of fats. The long-term effects of PUFAs on satiety, however, remain
      unknown. The aim of this study was to determine subjective and physiological
      hunger and satiety responses to high-fat (HF) meals before and after a 7-d PUFA
      rich diet. METHODS: Twenty-six, healthy weight (body mass index 18-24.9 kg/m2),
      sedentary adults were randomly assigned to either a 7-d PUFA-rich diet (n = 8 men
      and n = 8 women) or a 7-d control diet (n = 5 men and n = 5 women). After a 3-d
      lead-in diet, participants reported for the baseline visit where anthropometrics,
      fasting visual analog scale (VAS) measurements, and a fasting blood sample were
      collected. Then, two HF meals (breakfast and lunch) were consumed. Postprandial
      blood draws and VAS measures were collected approximately every 30 min for 4 h
      after each meal, for a total of 8 h. RESULTS: From pre- to post-PUFA-rich diet,
      there was a decrease in fasting ghrelin (P < 0.05) and an increase in fasting
      peptide YY (PYY; P < 0.05); however, there were no changes in fasting insulin or
      leptin concentrations. The postprandial response for PYY was higher after the
      PUFA-rich diet visit compared to baseline (P < 0.01). However, there were no
      differences in the postprandial response for ghrelin, insulin, leptin, or VAS
      measures from pre- to post-diet in either the PUFA-rich diet or control (ns).
      CONCLUSION: A PUFA-rich diet consumed for 7 d favorably altered fasting and
      postprandial physiological markers of hunger and satiety; yet, did not alter
      subjective ratings of hunger or fullness.

PMID- 28760424
TI  - Anthocyanins in chokeberry and purple maize attenuate diet-induced metabolic
      syndrome in rats.
AB  - OBJECTIVE: Increased consumption of fruits and vegetables as functional foods
      leads to the reduction of signs of metabolic syndrome. The aim of this study was
      to measure and compare cardiovascular, liver, and metabolic parameters following
      chronic administration of the same dose of anthocyanins either from chokeberry
      (CB) or purple maize (PM) in rats with diet-induced metabolic syndrome. METHODS:
      Male Wistar rats were fed a maize starch (C) or high-carbohydrate, high-fat diet
      (H) and divided into six groups for 16 wk. The rats were fed C, C with CB or PM
      for the last 8 wk (CCB or CPM), H, H with CB or PM for the last 8 wk (HCB or
      HPM); CB and PM rats received ~8 mg anthocyanins/kg daily. The rats were
      monitored for changes in blood pressure, cardiovascular and hepatic structure and
      function, glucose tolerance, and adipose tissue mass. RESULTS: HCB and HPM rats
      showed reduced visceral adiposity index, total body fat mass, and systolic blood
      pressure; improved glucose tolerance, liver, and cardiovascular structure and
      function; decreased plasma triacylglycerols and total cholesterol compared with H
      rats. Inflammatory cell infiltration was reduced in heart and liver. CONCLUSION:
      CB and PM interventions gave similar responses, suggesting that anthocyanins are
      the bioactive molecules in the attenuation or reversal of metabolic syndrome by
      prevention of inflammation-induced damage.

PMID- 28760425
TI  - Influence of selenium supplementation on patients with inflammation: A pilot
      double blind randomized study.
AB  - OBJECTIVE: The aim of the study was to analyze the effect of selenium
      supplementation on patients with inflammation receiving PN. METHODS: This double
      blind randomized study included 20 hospitalized patients experiencing an
      inflammatory process while being fed by PN, who were monitored in three stages:
      first 72 h (0), day 7 (1), and day 14 (2) of PN. The supplemented patients group
      (G+S) received 60 MUg/d (0.75 MUmol) of selenium as selenious acid which was
      added to the PN bag. The nonsupplemented group (G-S) did not receive selenium.
      The concentration range of 84 to 100 MUg/L (1.07-1.27 MUmol/L) was used as a
      reference of plasma selenium. RESULTS: The study included 20 patients (8 G+S and
      12 G-S) mainly diagnosed with cancer and/or sepsis. Most of them were
      hospitalized in the intensive care unit and were receiving PN for clinical
      reasons. Plasma selenium was greater in the G+S than in the G-S (P = 0.05) in two
      stages (0 and 1). Since the start of assessment, C-reactive protein (CRP) levels
      were elevated; however, there was no statistical difference in CRP values between
      groups (P > 0.05). There was no significant change of glutathione peroxidase over
      time or between groups (P > 0.05). CONCLUSION: The selenium concentration was
      greater in the G+S than in the G-S, acting independently from CRP behavior.
      However, supplementation was not enough to reach the reference values.

PMID- 28760426
TI  - Body composition measurement using computed tomography: Does the phase of the
      scan matter?
AB  - OBJECTIVES: The aim of this study was to determine, from the methodologic
      standpoint, the effect of the presence or absence of intravenous contrast on body
      composition variables obtained by analysis of computed tomography (CT) images.
      METHODS: Triphasic abdominal (noncontrast, arterial phase, and portovenous phase
      contrast) CT scans from 111 patients were analyzed by two independent assessors
      at the third lumbar vertebral level using SliceOmatic software (version 5.0,
      TomoVision, Montreal, Canada). Variables included skeletal muscle index (SMI),
      fat and fat-free mass (FM and FFM, respectively), and mean skeletal muscle
      Hounsfield units (SMHU). RESULTS: Mean SMHU was lowest in the noncontrast phase
      (29.4, standard deviation [SD] 8.9 HU), followed by arterial (32.4, SD 9.3 HU)
      then portovenous phases (34.9, SD 9.4 HU). The mean skeletal muscle attenuation
      was significantly different depending on the phase of the scan in which the
      images were obtained. Calculated FM was significantly lower in both arterial
      (28.6, SD 8.8 kg, P < 0.0001) and portovenous phase scans (28.5, SD 8.9 kg, P <
      0.0001) when compared with noncontrast (29.2, SD 8.9 kg). The mean FFM was not
      significantly different as measured on noncontrast, arterial, or portovenous
      phase CT scans (48, SD 11.2; 48.1, SD 9.8; and 48.6, SD 10.2 kg, respectively).
      No difference was seen in SMI. Interobserver reliability was high. CONCLUSIONS:
      The definition of myosteatosis should include a standardized phase of CT for
      analysis and this should be incorporated within its definition. However, as the
      magnitudes of the differences were relatively small, the effect of the phase of
      the scan on predicting outcome needs to be determined.

PMID- 28760427
TI  - Anthropometric and lipid profile of individuals with severe obesity carrying the
      fatty acid-binding protein-2 Thr54 allele.
AB  - OBJECTIVE: The aim of this study was to evaluate the anthropometric and lipid
      profiles of individuals being considered for bariatric surgery, taking into
      account the presence of the Thr54 allele of the fatty acid-binding protein-2
      (FABP-2) gene (rs1799883), and dietary intake. METHODS: In a cross-sectional
      study, 120 participants being evaluated for bariatric surgery were asked to keep
      24-h dietary records (R24 h) for 3 d, and to collect a 24-h urine sample for
      measurement of urea (as an assessment of the adequacy of food records) during day
      3 of the diet record; a fasting blood sample for laboratory and genetic
      evaluations was collected. RESULTS: When considering the whole sample, no
      significant differences were found; however, those who complied with the R24 h (n
      = 43) had more years of schooling and higher saturated fat intake, but lower
      weight and body mass index (BMI). When analyzing only the completers, the Thr54
      allele carriers showed higher body weight (P = 0.02), BMI (P = 0.03), hip
      circumference (P = 0.02), basal metabolic rate (P = 0.02), and homeostatic model
      assessment-beta (P = 0.04) compared with those who were homozygous for Ala54.
      CONCLUSION: When the participants complied with the R24 h, Thr54 carriers were
      shown to have higher anthropometric parameters and higher homeostatic model
      assessment-beta values than those with the wild genotype, but the lipid profile
      resulted similar in both carriers and noncarriers.

PMID- 28760428
TI  - Influence of nutritional status in the diagnosis of sarcopenia in nursing home
      residents.
AB  - OBJECTIVES: Malnutrition and sarcopenia frequently coexist in elderly patients.
      The aim of this study was to assess the effect of nutritional status in the
      diagnosis of sarcopenia in nursing home residents. METHODS: A cross-sectional
      study was performed with data collected from 339 elderly patients living in five
      nursing homes. Sarcopenia was defined according to the consensus definition of
      the European Working Group on Sarcopenia in Older People. Body mass composition
      was assessed using bioimpedance analysis, handgrip strength using a dynamometer,
      and physical performance by 5-m gait speed test. The nutritional status of
      residents was assessed using the Mini Nutritional Assessment (MNA). RESULTS: Of
      436 patients, 339 (77.8%) were included. The mean age of participants was 84.9 y
      and 64.3% were women. More than one-third (38.1%) of the population had
      sarcopenia, with a higher prevalence in women (39.4%). According to the MNA,
      32.4% of participants were at risk for malnutrition and 42.5% were malnourished.
      When analyzed together, the presence of malnutrition plus malnutrition risk,
      there was no difference between individuals with or without sarcopenia. However,
      the presence of malnutrition was statistically higher in individuals with
      sarcopenia compared with those without it. The prevalence of malnutrition was
      highest in individuals with low handgrip strength (62.8%), and in participants
      with severe sarcopenia. There were no significant differences in calf
      circumference between sarcopenic and nonsarcopenic participants. In the
      multivariate logistic regression analysis, body mass index <22 kg/m2 and age >80
      y remained predictive of sarcopenia status after adjustment. CONCLUSION:
      Prevalence of sarcopenia and malnutrition were significant in this population,
      especially in women. Approximately two-thirds of sarcopenic individuals were
      malnourished. A low body mass index may be a better predictor of sarcopenia in
      this population than a small calf circumference (<1 cm).

PMID- 28760429
TI  - Evidence-based recommendations and expert consensus on enteral nutrition in the
      adult patient with diabetes mellitus or hyperglycemia.
AB  - OBJECTIVE: The aim of this study was to develop evidence-based recommendations
      for glycemic control of patients with diabetes mellitus or stress hyperglycemia
      who are receiving enteral nutrition (EN). METHODS: A Delphi survey method using
      Grading Recommendations Assessment, Development and Evaluation criteria was
      utilized for evaluation of suitable studies. RESULTS: In patients with diabetes
      or stress hyperglycemia who were on EN support, the following results were found:
      CONCLUSIONS: These recommendations and suggestions regarding enteral feeding in
      patients with diabetes and hyperglycemia have direct clinical applicability.

PMID- 28760430
TI  - Is maternal body mass index associated with neonatal mortality? A pooled analysis
      of nationally representative data from nine Asian countries.
AB  - OBJECTIVE: Children born to mothers with abnormal body mass index (BMI) have
      increased risk for mortality. The aim of this study was to investigate whether
      maternal BMI is a risk factor for neonatal death in select Asian countries,
      including the nature of association between maternal BMI and the discrete timing
      of neonatal death. METHODS: Nationally representative, the standard Demographic
      and Health Survey data from nine Asian countries were used. In all, 55 629
      mothers reported their index birth; 840 reported neonatal mortality. Descriptive
      statistics and multivariate logistic regression analyses were applied to attain
      the study objective. RESULTS: Overweight mothers had higher odds of neonatal
      mortality than mothers with optimum weight. No significant association was
      registered for obese mothers, possibly due to insufficient power. During the
      first 7 d (0-1 and 2-6 d) of birth, children born to overweight mothers had
      higher odds of dying, whereas for the remaining period (7-27 d), maternal
      underweight was the risk factor for neonatal mortality. CONCLUSION: Interventions
      should target high-risk pregnancies to reduce the rate of neonatal mortality.
      With the help of community health workers or physicians, preconception counseling
      of prospective mothers with abnormal BMI should be devised. If conceived,
      underweight or overweight or obese women should be marked as high-risk pregnancy
      during their antenatal care visits, and they must be encouraged for delivery at
      an institution equipped with an emergency obstetric and neonatal care unit.

PMID- 28760431
TI  - Predicting clinical outcomes using phase angle as assessed by bioelectrical
      impedance analysis in maintenance hemodialysis patients.
AB  - OBJECTIVE: Protein-energy wasting is common in patients on hemodialysis and is an
      independent risk factor for adverse events. The aim of this study was to
      retrospectively investigate whether phase angle (PA), known as a nutritional
      marker, can predict various clinical outcomes in patients with end-stage renal
      disease (ESRD) who are receiving hemodialysis. METHODS: Using bioelectrical
      impedance analysis (BIA), PA was obtained every 6 mo, and patients were divided
      into two groups according to baseline PA: group A included patients with PA >=4.5
      degrees , and group B included patients with PA <4.5 degrees . RESULTS: We
      followed 142 patients for a median of 29 mo (12-42 mo). We found that a decrease
      in PA was associated with an increased risk for death that persisted after
      adjusting for age, sex, and comorbidities (hazard ratio [HR], 0.56; 95%
      confidence interval [CI], 0.33-0.97). Cardiovascular events were not associated
      with PA (P = 0.685). We found that PA predicted the occurrence of infection,
      independent of age, sex, and comorbidities (HR, 0.65; 95% CI, 0.45-0.94).
      Although levels of hemoglobin did not differ between groups during the study
      period, patients in group B received higher doses of erythropoiesis-stimulating
      agents and intravenous iron than those in group A (P = 0.004 and 0.044,
      respectively). In longitudinal analyses, we did not find increases in PA over
      time in patients who had a mean dialysis adequacy >=1.4, daily protein catabolic
      rate >=1.2 g/kg, or total carbon dioxide level >=22 mmol/L. CONCLUSIONS: PA
      assessed in a simple manner using BIA provides practical information to predict
      clinical outcomes in ESRD patients on maintenance hemodialysis.

PMID- 28760432
TI  - Elderly patients on hemodialysis have worse dietary quality and higher
      consumption of ultraprocessed food than elderly without chronic kidney disease.
AB  - OBJECTIVES: The multiple dietary restrictions recommended to patients on
      hemodialysis (HD), coupled with conditions imposed by aging, may lead to poor
      dietary quality in these patients. The aim of this study was to investigate the
      dietary quality and consumption of ultraprocessed food by elderly patients on HD
      and those without chronic kidney disease (CKD). Additionally, diets on the day of
      dialysis and on nondialysis days were evaluated. METHODS: This was a cross
      sectional study conducted with 153 noninstitutionalized elderly patients on HD
      (Elder-HD) and 47 non-CKD elderly (Elder-Healthy) aged >=60 y. From a 3-d food
      record, the dietary quality was assessed using the Brazilian Healthy Eating Index
      Revised (BHEI-R) and the energy contribution of food-processing groups. RESULTS:
      Compared with the Elder-Healthy group, the Elder-HD group showed a lower total
      BHEI-R score (P < 0.05). On the weekdays, the Elder-HD group showed lower scores
      (P < 0.05) of whole fruit, dark green vegetables and legumes, meat, eggs, and
      legumes, whereas total cereals showed a higher score (P < 0.05). When furthering
      the analysis on the Elder-HD group, although the total BHEI-R score did not
      differ among the days assessed, the components whole fruit, dark green
      vegetables, and legumes had lower scores (P < 0.05) on the day of dialysis, and
      the opposite was observed for milk and dairy products. Moreover, the Elder-HD
      showed a higher (P < 0.05) contribution of processed and ultraprocessed foods and
      lower (P < 0.05) contribution of natural or minimally processed foods.
      CONCLUSION: The Elder-HD group showed poorer dietary quality and higher
      consumption of processed and ultraprocessed foods than the Elder-Healthy group.
      Moreover, when compared with the nondialysis day, these patients exhibited worse
      dietary quality, on the day of dialysis.

PMID- 28760433
TI  - Branched-chain amino acid supplementation in treatment of liver cirrhosis:
      Updated views on how to attenuate their harmful effects on cataplerosis and
      ammonia formation.
AB  - Branched-chain amino acid (BCAA; valine, leucine, and isoleucine) supplementation
      is common for patients with liver cirrhosis due to decreased levels of BCAA in
      the blood plasma of these patients, which plays a role in pathogenesis of hepatic
      encephalopathy and cachexia. The unique pharmacologic properties of BCAA also are
      a factor for use as supplementation in this population. In the present article,
      BCAA is shown to provide nitrogen to alpha-ketoglutarate (alpha-KG) for synthesis
      of glutamate, which is a substrate for ammonia detoxification to glutamine (GLN)
      in the brain and muscles. The article also demonstrates that the favorable
      effects of BCAA supplementation might be associated with three adverse effects:
      draining of alpha-KG from tricarboxylic acid cycle (cataplerosis), increased GLN
      content and altered glutamatergic neurotransmission in the brain, and activated
      GLN catabolism to ammonia in the gut and kidneys. Cataplerosis of alpha-KG can be
      attenuated by dimethyl-alpha-ketoglutarate, l-ornithine-l-aspartate, and
      ornithine salt of alpha-KG. The pros and cons of GLN elimination from the body
      using phenylbutyrate (phenylacetate), which may impair liver regeneration and
      decrease BCAA levels, should be examined. The therapeutic potential of BCAA might
      be enhanced also by optimizing its supplementation protocol. It is concluded that
      the search for strategies attenuating adverse and increasing positive effects of
      the BCAA is needed to include the BCAA among standard medications for patients
      with cirrhosis of the liver.

PMID- 28760434
TI  - Micronutrient status (calcium, zinc, vitamins D and E) in patients with medullary
      thyroid carcinoma: A cross-sectional study.
AB  - OBJECTIVE: The aim of this study was to evaluate the micronutrient status of
      Iranian patients with medullary thyroid carcinoma (MTC) and to analyze potential
      relationships with respect to MTC risk. METHODS: This was a cross-sectional study
      (Tehran Thyroid Cancer Survey 2015-2016). We measured and compared preoperative
      serum calcium, zinc, and vitamins D and E in patients with MTC and healthy
      controls. Forty cases with MTC and 40 (age-, sex-, and body mass index-matched)
      healthy controls voluntarily participated in the project. RESULTS: Serum calcium,
      zinc, and vitamin D and E concentrations were lower in the patients with cancer
      (PCa < 0.001, PZn = 0.01, PD = 0.056, PE = 0.002) than in the healthy controls.
      We found that serum calcium remarkably associated with enhanced risk for thyroid
      cancer (odds ratio [OR], 6.5; P = 0.001). Likewise, serum vitamin E was linked to
      the risk for cancer (OR, 1.31; P = 0.056). Moreover, serum zinc was correlated
      with vitamin E and calcium (r = +0.23; P = 0.04 and r = +0.25, P = 0.03;
      respectively). We also observed a correlation between calcium and vitamin E (r =
      +0.27; P = 0.02). CONCLUSIONS: A multiple-micronutrient decrease was confirmed in
      patients with MTC. A low serum calcium level was a potent risk factor for MTC.
      Findings from the present study suggest that dietary intake and/or
      supplementation of micronutrients, especially calcium and vitamin E, may be
      beneficial in reducing the risk for thyroid cancer.

PMID- 28760435
TI  - Nutrigenomics of omega-3 fatty acids: Regulators of the master transcription
      factors.
AB  - It is well known that omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs)
      control some key molecular cell mechanisms, resulting in a beneficial role in
      inflammatory diseases. Such mechanisms are complex and reflect the diversity of
      their functions, mainly as modulators of the dynamic properties of membranes,
      regulators of gene expression, and precursors of active mediators. The aim of
      this review is to summarize the state of the art of the effects and mechanisms by
      which omega-3 LC-PUFAs such as eicosapentaenoic acid (EPA, C22:5 omega-3) and
      docosahexaenoic acid (DHA, C22:6 omega-3) regulate different metabolic processes
      to maintain homeostasis. Thus, we describe some aspects of these fatty acids-from
      their structural function in cell membranes to their role as regulators of gene
      expression, mainly in lipid metabolism. However, further studies are required to
      elucidate these actions and to have a better understanding in regard to the
      beneficial effects of omega-3 LC-PUFAs in the pathogenesis of several diseases as
      well as their functions as nutrients with protective action to avoid or delay
      development of these diseases. Furthermore, it is necessary to highlight the lack
      of comprehensive studies including nutritional, biochemical, genetic, and immune
      aspects to identify specific molecular mechanisms involved in the beneficial
      effects of consumption of DHA (C22:6 omega-3) and EPA (C22:5 omega-3) and their
      metabolic derivatives on health promotion.

PMID- 28760436
TI  - Impact of the structure and dose of protein intake on clinical and metabolic
      outcomes in critically ill children: A systematic review.
AB  - OBJECTIVE: The aim of this study was to describe the effects of structure/type
      and total amount of protein intake on protein balance and clinical outcomes in
      critically ill children. METHODS: We conducted a systematic review of relevant
      literature on Embase, PubMed/Medline, Web of Science, Scopus, and Latin American
      and Caribbean Health Sciences. A partial gray literature search was undertaken
      and the reference lists of the selected articles were searched manually.
      Observational and clinical trials that evaluated the total protein intake,
      structure of the protein source, or both, in critically ill children were
      included. Nitrogen balance and clinical outcomes (mortality, length of stay, and
      duration of mechanical ventilation) were the main outcomes of interest. RESULTS:
      We found 18 eligible studies, of which 17 assessed the quantity and one described
      protein structure in relation to the outcomes. In all, 2118 pediatric critically
      ill patients <18 y of age were included. The total daily protein intake ranged
      from 0.67 to 4.7 g/kg. Average daily total protein intake >1.1 g/kg, especially
      >1.5 g/kg, was associated with positive protein balance and lower mortality.
      CONCLUSION: In critically ill children, total daily protein intake >1.1 g/kg was
      associated with positive effects on clinical outcomes and protein balance. The
      existing data are not sufficient for determining the optimal structure of protein
      delivered by enteral route in critically ill children.

PMID- 28760437
TI  - Hyponatremia in refractory congestive heart failure patients treated with
      icodextrin-based peritoneal dialysis: A case series.
AB  - Severe congestive heart failure (CHF) patients are prone to hyponatremia.
      Peritoneal dialysis (PD) is increasingly used for long-term management of
      refractory CHF patients. The glucose polymer icodextrin was proposed to be a good
      option for fluid removal in such patients. A small, although statistically
      significant reduction in serum sodium (~2mmol/l) consistently observed in
      multiple trials, is considered as not clinically relevant. Here we reported five
      refractory CHF patients who demonstrated sodium drop by median of 8meq/l (range
      5.4-8.3meq/l) after icodextrin was added to their program. It seems that
      icodextrin may contribute to clinically relevant hyponatremia if the hyponatremia
      is compounded by other factors. Patients with extremely severe congestive heart
      failure are susceptible to this complication.

PMID- 28760438
TI  - Elucidating functional differences between cortical gyri and sulci via sparse
      representation HCP grayordinate fMRI data.
AB  - The highly convoluted cerebral cortex is characterized by two different
      topographic structures: convex gyri and concave sulci. Increasing studies have
      demonstrated that cortical gyri and sulci exhibit different structural
      connectivity patterns. Inspired by the intrinsic structural differences between
      gyri and sulci, in this paper, we present a data-driven framework based on sparse
      representation of fMRI data for functional network inferences, then examine the
      interactions within and across gyral and sulcal functional networks and finally
      elucidate possible functional differences using graph theory based properties. We
      apply the proposed framework to the high-resolution Human Connectome Project
      (HCP) grayordinate fMRI data. Extensive experimental results on both resting
      state fMRI data and task-based fMRI data consistently suggested that gyri are
      more functionally integrated, while sulci are more functionally segregated in the
      organizational architecture of cerebral cortex, offering novel understanding of
      the byzantine cerebral cortex.

PMID- 28760439
TI  - Preventive and therapeutic effect of brozopine on stroke in Dahl Salt-sensitive
      hypertensive rats.
AB  - Our aim was to explore the preventive and therapeutic effects of sodium (+/-)-5
      bromo-2-(alpha-hydroxypentyl) benzoate (brand name: brozopine, BZP) on stroke in
      Dahl Salt-sensitive (Dahl-SS) hypertensive rats. Dahl-SS rats were fed a high
      salt diet to observe the effect of BZP on blood pressure, and brain, heart, and
      kidney tissues. Additionally, the incidence of stroke was recorded according to
      the neurological score. The relative mechanisms investigated included anti
      oxidative effects and anti-platelet aggregation. BZP reduced the incidence of
      stroke, neuronal necrosis in the brain, and cell swelling and inflammatory
      infiltration in the kidney. Its mechanisms were related to the increased
      activities of gluthatione peroxidase and catalase and the decreased level of
      plasma nitric oxide. BZP inhibited arachidonic acid (AA) - induced platelet
      aggregation (IC50: 12uM) rather than that of adenosine diphosphate (ADP) - and/or
      thrombin-induced platelet aggregation in vitro. Interestingly, BZP inhibited ADP
      , thrombin-, or AA-induced platelet aggregation and elevated the level of AMP
      activated protein kinase, cyclic guanosine monophosphate, and vasodilator
      stimulated-phosphoprotein, and attenuated ATP contents and mitogen-activated
      protein kinase levels in platelet and inhibited thrombus formation in a carotid
      artery thrombosis model, dose-dependently, in Dahl-SS hypertensive-induced stroke
      rats. In conclusion, BZP can have therapeutic and preventive effects on stroke in
      Dahl-SS hypertensive rats, the mechanisms of which may be related to anti
      oxidant, anti-platelet aggregation and anti-thrombus formation.

PMID- 28760440
TI  - The effect of electroacupuncture on proteomic changes in the motor cortex of 6
      OHDA Parkinsonian rats.
AB  - Electroacupuncture (EA) has been reported to alleviate motor deficits in
      Parkinson's disease (PD) patients, and PD animal models. However, the mechanisms
      by which EA improves motor function have not been investigated. We have employed
      a 6-hydroxydopamine (6-OHDA) unilateral injection induced PD model to investigate
      whether EA alters protein expression in the motor cortex. We found that 4weeks of
      EA treatment significantly improved spontaneous floor plane locomotion and
      rotarod performance. High-throughput proteomic analysis in the motor cortex was
      employed. The expression of 54 proteins were altered in the unlesioned motor
      cortex, and 102 protein expressions were altered in the lesioned motor cortex of
      6-OHDA rats compared to sham rats. Compared to non-treatment PD control, EA
      treatment reversed 6 proteins in unlesioned and 19 proteins in lesioned motor
      cortex. The present study demonstrated that PD induces proteomic changes in the
      motor cortex, some of which are rescued by EA treatment. These targeted proteins
      were mainly involved in increasing autophagy, mRNA processing and ATP binding and
      maintaining the balance of neurotransmitters.

PMID- 28760441
TI  - Retinal metabolism: A comparative look at energetics in the retina.
AB  - The retina is part of the central nervous system, and shares the
      characteristically high metabolism of the brain. The high energy demand of the
      retina is normally matched with a large supply of metabolites. When supply does
      not equal demand (e.g. if retinal blood flow is impaired), retinal neurons are at
      risk of excitotoxic cell death and vision is impaired or lost. Understanding the
      energetic budget of the retina is therefore crucial for understanding the
      pathology and treatment of retinal disease. In this minireview I give an overview
      of the energetics of the retina, with a focus on lessons learnt from comparative
      physiology. Retinas of all species studied thus far receive blood flow from
      choroidal capillaries. Additionally, fish, reptiles, and birds each have unique
      structures to increase metabolite supply. Primates and some mammals also have
      intra- and supraretinal vasculature to supply the retina, while other mammals
      rely solely on the choroid at the cost of retinal thickness. Neuroglobin, an
      oxygen-binding protein, may assist in oxygen delivery to counteract large
      diffusion distances from capillaries to mitochondria. Energy demand differs among
      models, as does mitochondrial location. More ATP is consumed in the dark due to
      Na+/K+ ATPase activity to counteract the dark current, whereas phototransduction
      dominates ATP demand in the light. Photoreceptor metabolism is therefore
      especially high, and may be sustained with phosphocreatine and lactate shuttles.
      This comparative physiology approach raises new research questions, and suggests
      caution in comparing animal models of retinal disease, as they differ greatly in
      vasculature and energetics.

PMID- 28760442
TI  - Integrating a light-driven coenzyme regeneration system by expression of an
      alcohol dehydrogenase in phototrophic bacteria for synthesis of chiral alcohol.
AB  - Herein, we reported that Rhodobacter sphaeroides (R. sphaeroides) can be
      engineered by heterologous expression of an alcohol dehydrogenase (adh) from
      Leifsonia sp. to build a light-driven cofactor regeneration system for synthesis
      of chiral alcohol. The model substrate, 3'-chloroacetophenone, can be reduced by
      the engineered R. sphaeroides to (R)-1-(3-chlorophenyl) ethanol with an
      enantiomeric excess (e.e.) value of more than 99% in an n-hexane/aqueous biphasic
      media. This system, which is fully controlled by light, exhibited potential power
      to be an alternative cofactor regeneration platform for cheap synthesis of
      various chiral alcohols via the cloning other oxidoreductases with diverse
      characteristics.

PMID- 28760443
TI  - Self-cycling fermentation for 1,3-propanediol production: Comparative evaluation
      of metabolite flux in cell recycling, simple batch and continuous processes using
      Lactobacillus brevis N1E9.3.3 strain.
AB  - The microbial conversion of biodiesel derived crude glycerol to 1,3-propanediol
      (1,3-PDO) has attained high industrial value due to the broad range of
      applications as a monomer (1,3-PDO) in textile, cosmetic and polymer industries.
      This fine chemical through biological production addressed several limitations of
      the chemical process like high temperatures, pressure and expensive catalysts. In
      this study 1,3-propanediol production was achieved from a non-pathogenic lactic
      acid bacterial strain Lactobacillus brevis N1E9.3.3 in suspended and immobilized
      form under batch, sequential batch and continuous modes of fermentation. The
      microorganism was immobilized in polyurethane foam cubes. The effects of initial
      glycerol concentration on suspended and immobilized cells were investigated in
      stirred tank reactor. The maximum 1,3-PDO titers of 51.5g1,3-PDO/l and 42.59g1,3
      PDO/l with a yield of 0.64g1.3-PDO/gGlycerol and 0.53g1.3-PDO/gGlycerol using
      suspended and immobilized cells respectively was observed in batch fermentation
      with an initial glycerol concentration of 80g/l. In repeated batch (self-cycling)
      fermentation 78.3g/l 1,3-PDO with 0.65g1.3-PDO/gGlycerol yield and 0.65g/l/h
      productivity was observed at the end of 5th cycle. A constant yield between 0.3
      0.65g1.3-PDO/gGlycerol was observed with cell recycling using suspended and
      immobilized cells. The highest productivity of 1.735g1,3-PDO/l/h was observed in
      chemostat with immobilized cells.

PMID- 28760444
TI  - Cloning, expression and characterization of a iota-carrageenase from marine
      bacterium Wenyingzhuangia fucanilytica: A biocatalyst for producing iota
      carrageenan oligosaccharides.
AB  - iota-Carrageenan is an algal polysaccharide widely applied in the food industry.
      Specific glycoside hydrolases are valuable tools for modifying polysaccharides
      and producing oligosaccharides. In this study, the gene of a novel GH82 family
      iota-carrageenase was cloned from the genome of marine bacterium Wenyingzhuangia
      fucanilytica. The iota-carrageenase designated as Cgi82A was expressed in
      Escherichia coli, and its biochemical properties, kinetic constants and
      hydrolysis pattern were characterized. The enzyme could reach its highest
      activity at 25 degrees C, which is lower than all hitherto reported GH82 iota
      carrageenases. It was an endo-acting hydrolase, and could be utilized as a
      potential biocatalyst for producing iota-carrageenan oligosaccharides with
      different polymerization degrees. Cgi82A possessed relatively high substrate
      binding affinity and catalysis efficiency indicated by its kinetic constants (Km,
      1.12MUM;Kcat, 560.75s-1). Its major end product was iota-carrageenan
      tetrasaccharide. The acquiring of this novel enzyme would facilitate the future
      application of iota-carrageenan and its oligosaccharides.

PMID- 28760445
TI  - Coeliac disease.
AB  - Coeliac disease occurs in about 1% of people in most populations. Diagnosis rates
      are increasing, and this seems to be due to a true rise in incidence rather than
      increased awareness and detection. Coeliac disease develops in genetically
      susceptible individuals who, in response to unknown environmental factors,
      develop an immune response that is subsequently triggered by the ingestion of
      gluten. The disease has many clinical manifestations, ranging from severe
      malabsorption to minimally symptomatic or non-symptomatic presentations.
      Diagnosis requires the presence of duodenal villous atrophy, and most patients
      have circulating antibodies against tissue transglutaminase; in children,
      European guidelines allow a diagnosis without a duodenal biopsy provided that
      strict symptomatic and serological criteria are met. Although a gluten-free diet
      is an effective treatment in most individuals, a substantial minority develop
      persistent or recurrent symptoms. Difficulties adhering to a gluten-free diet
      have led to the development of non-dietary therapies, several of which are
      undergoing trials in human beings.

PMID- 28760446
TI  - In vitro to in vivo extrapolation of effective dosimetry in developmental
      toxicity testing: Application of a generic PBK modelling approach.
AB  - Incorporation of kinetics to quantitative in vitro to in vivo extrapolations
      (QIVIVE) is a key step for the realization of a non-animal testing paradigm, in
      the sphere of regulatory toxicology. The use of Physiologically-Based Kinetic
      (PBK) modelling for determining systemic doses of chemicals at the target site is
      accepted to be an indispensable element for such purposes. Nonetheless, PBK
      models are usually designed for a single or a group of compounds and are
      considered demanding, with respect to experimental data needed for model
      parameterization. Alternatively, we evaluate here the use of a more generic
      approach, i.e. the so-called IndusChemFate model, which is based on incorporated
      QSAR model parametrization. The model was used to simulate the in vivo kinetics
      of three diverse classes of developmental toxicants: triazoles, glycol ethers'
      alkoxyacetic acid metabolites and phthalate primary metabolites. The model
      required specific input per each class of compounds. These compounds were
      previously tested in three alternative assays: the whole-embryo culture (WEC),
      the zebrafish embryo test (ZET), and the mouse embryonic stem cell test (EST).
      Thereafter, the PBK-simulated blood levels at toxic in vivo doses were compared
      to the respective in vitro effective concentrations. Comparisons pertaining to
      relative potency and potency ranking with integration of kinetics were similar to
      previously obtained comparisons. Additionally, all three in vitro systems
      produced quite comparable results, and hence, a combination of alternative tests
      is still preferable for predicting the endpoint of developmental toxicity in
      vivo. This approach is put forward as biologically more plausible since plasma
      concentrations, rather than external administered doses, constitute the most
      direct in vivo dose metric.

PMID- 28760447
TI  - Should we broaden indications for anti-JCV antibody tests in multiple sclerosis
      patients? YES.

PMID- 28760448
TI  - Progesterone lipid nanoparticles: Scaling up and in vivo human study.
AB  - This investigation describes a scaling up study aimed at producing progesterone
      containing nanoparticles in a pilot scale. Particularly hot homogenization
      techniques based on ultrasound homogenization or high pressure homogenization
      have been employed to produce lipid nanoparticles constituted of tristearin or
      tristearin in association with caprylic-capric triglyceride. It was found that
      the high pressure homogenization method enabled to obtain nanoparticles without
      agglomerates and smaller mean diameters with respect to ultrasound homogenization
      method. X-ray characterization suggested a lamellar structural organization of
      both type of nanoparticles. Progesterone encapsulation efficiency was almost 100%
      in the case of high pressure homogenization method. Shelf life study indicated a
      double fold stability of progesterone when encapsulated in nanoparticles produced
      by the high pressure homogenization method. Dialysis and Franz cell methods were
      performed to mimic subcutaneous and skin administration. Nanoparticles
      constituted of tristearin in mixture with caprylic/capric triglyceride display a
      slower release of progesterone with respect to nanoparticles constituted of pure
      tristearin. Franz cell evidenced a higher progesterone skin uptake in the case of
      pure tristearin nanoparticles. A human in vivo study, based on tape stripping,
      was conducted to investigate the performance of nanoparticles as progesterone
      skin delivery systems. Tape stripping results indicated a decrease of
      progesterone concentration in stratum corneum within six hours, suggesting an
      interaction between nanoparticle material and skin lipids.

PMID- 28760449
TI  - Tumor microenvironment determines response to a heat-activated thermosensitive
      liposome formulation of cisplatin in cervical carcinoma.
AB  - Significant heterogeneity in the tumor microenvironment of human cervical cancer
      patients is known to challenge treatment outcomes in this population. The current
      standard of care for cervical cancer patients is radiation therapy and concurrent
      cisplatin (CDDP) chemotherapy. Yet this treatment strategy fails to control loco
      regional disease in 10-30% of patients. In order to improve the loco-regional
      control rate, a thermosensitive liposome formulation of CDDP (HTLC) was developed
      to increase local concentrations of drug in response to mild hyperthermia (HT).
      The HTLC formulation in combination with local HT demonstrated a significant
      therapeutic advantage in comparison to free drug and LipoplatinTM in ME-180 and
      SiHa xenograft models of human cervical cancer, as well as in four distinct
      cervical patient-derived xenograft models. Differential response to HTLC+HT
      treatment was observed between the ME-180 and SiHa tumor models. Tumor doubling
      time, in vitro cell sensitivity, and tumor drug accumulation were found to be non
      predictive of treatment efficacy. Rather, tumor microenvironment parameters, in
      particular elevated levels of both tumor hypoxia and associated stromal content,
      were found to serve as the overriding factors that limit drug efficacy. The
      prognostic value of these markers may enable stratification of cervical cancer
      patients for implementation of personalized medicine in the clinical setting.

PMID- 28760450
TI  - Achieving optimal welfare for the Nile hippopotamus (Hippopotamus amphibius) in
      North American zoos and aquariums.
AB  - Compared to other megafauna managed in zoos and aquariums, the current state of
      welfare for the Nile hippopotamus (Hippopotamus amphibius) is poorly understood.
      Complex behavior and physiological characteristics make hippos a difficult
      species to manage. Thus, hippos in managed care are currently at risk for a
      decreased state of welfare. In an effort to assess and improve conditions for
      this species, a survey was administered to North American institutions housing
      Nile hippos. This assessment utilized a multiple-choice format and consisted of
      questions relating to group structure, behavior, and exhibit design, allowing for
      the creation of cross-institutional, welfare-based analysis. Responses were
      gathered from 85.29% of the institutions to which the survey was distributed.
      Despite recommendations for maintaining groups of at least five individuals
      (Forthman, 1998), only 34.25% of hippos in North America were housed in groups of
      three or more. The survey also highlighted that 39.29% of institutions secure
      their hippos in holding areas overnight, despite their highly active nocturnal
      propensities. A better understanding of hippo behavior and environmental
      preferences can be used to inform wellness-oriented management practices to
      achieve a state of "optimal welfare".

PMID- 28760451
TI  - Light driven reactions in model algae.

PMID- 28760452
TI  - Marking the Milestones in Structural Biology.

PMID- 28760454
TI  - In silico analysis of ChtBD3 domain to find its role in bacterial pathogenesis
      and beyond.
AB  - Chitin binding domain 3, known by the acronym ChtBD3, is a domain in the enzymes
      and proteins of several pathogenic virus, bacteria and fungi. As this domain is
      evolutionarily-conserved in virulence factors of these infectious agents, its
      detailed investigation is of clinical interest. In this regard, the current in
      silico study analyzed ChtBD3 domain distribution in bacterial proteins present in
      publicly-available SMART (simple modular architecture research tool) database.
      Also, the co-occurring domains of ChtBD3 in the studied proteins were mapped to
      understand positional rearrangement of the domain and consequent functional
      diversity. Custom-made scripts were used to interpret the data and to derive
      patterns. As expected, interesting results were obtained. ChtBD3 domain co
      occurred with other critical domains like peptidase, glycol_hydrolase, kinase,
      hemagglutinin-acting, collagen-binding, among others. The findings are expected
      to be of clinical relevance.

PMID- 28760453
TI  - In vitro evaluation of the antibacterial potential and modification of antibiotic
      activity of the Eugenia uniflora L. essential oil in association with led lights.
AB  - Due to the great biodiversity of its flora, Brazil provides combat tools against
      bacterial resistance with the utilization of natural products with vegetable
      origin. Therefore, the present study had as its objective to evaluate the
      antibacterial potential of the Eugenia uniflora essential oil (EuEO) in vitro, as
      well as to analyze the modulatory effect of the oil against antibiotics by
      gaseous contact and to compare them when associated with a LED apparatus. The
      chemical components were characterised by gas chromatography which revealed the
      presence of the isoflurane-germacrene, considered the major component (61.69%).
      The MIC obtained from the EuEO was >=256 MUg/mL for S. aureus and >=1024 MUg/mL
      for E. coli. When combined with antibiotics, the EuEO presented synergism
      reducing the MIC when associated, with the exception of gentamicin against E.
      coli, where an antagonistic effect was observed. The was an interference of the
      EuEO over the activity of ciprofloxacin when associated with red and blue LED
      lights, increasing the inhibition halos against S. aureus and E. coli.
      Norfloxacin presented similar results to ciprofloxacin against S. aureus
      bacteria. When combined, norfloxacin and the EuEO presented synergism against S.
      aureus, which did not occur in the combination with ciprofloxacin. Interference
      occurred only with blue light for E. coli. Thus, it was observed that the EuEO
      causes changes in the activity of antibiotics, the same occurring with the use of
      LED lights, without significant differences in the association of the oil and the
      lights with the antibiotics tested. Further research is needed to elucidate the
      modulatory effects of the EuEO, as well as its association with LED lights.

PMID- 28760455
TI  - Association between virulence profile, biofilm formation and phylogenetic groups
      of Escherichia coli causing urinary tract infection and the commensal gut
      microbiota: A comparative analysis.
AB  - Variety of virulence factors are involved in the pathogenicity of Escherichia
      coli, the common cause of the urinary tract infections (UTIs). The aim of this
      study was to determine some virulence factors involved in the pathogenicity and
      the phylogenetic grouping of E. coli from UTIs compared with the E. coli isolates
      from gut microbiota (fecal flora). The isolates were tested for biofilm
      formation, haemagglutination, cell surface hydrophobicity (CSH), hemolysin
      production, phylogenetic grouping and the distribution of 6 known virulence
      genes. Isolates from UTIs showed a significantly higher prevalence of
      haemagglutination and hemolysin production compared with fecal flora (P <= 0.05),
      while biofilm formation and cell surface hydrophobicity (CSH) were not
      significantly different among the groups. Prevalence of virulence genes fimH,
      kpsMT ll, iutA, sat, hlyA, and cnf1 among all isolates were: 94.5%, 66.95%,
      67.8%, 39%, 23.07% and 21.08%, respectively. The genes for hlyA, cnf1, kpsMT ll
      were found to be higher in UTI isolates compared to fecal flora (P <= 0.05). The
      frequency of the isolates in the phylogenetic groups B2, D, A and B1 were 36.7%,
      31.3%, 16.2% and 15.6%, respectively. All the virulence genes except fimH were
      found to be significantly higher in the isolates of groups B2 and D. The results
      suggests that certain factors are necessary for the host colonization and
      infection and they are common in both virulent and non-virulent strains, and that
      the strains in the groups A and B1 having the lower virulence factors must
      acquire these factors when the condition is in favor of their dissemination to
      the urinary tract. In contrast the isolates in the groups B2 and D appeared to be
      potentially virulent.

PMID- 28760456
TI  - Effect of vitamin C on tissue damage and oxidative stress following tunica
      vaginalis flap coverage after testicular torsion.
AB  - AIM OF THE STUDY: The aim was to investigate the protective effect of vitamin C
      on tissue damage and oxidative stress following tunica albuginea incision with
      tunica vaginalis flap coverage for testicular torsion. MATERIALS AND METHODS:
      Adult male Wistar rats were randomly divided into two experimental groups. The
      first group experienced 5h of testicular torsion followed by treatment with
      vitamin C alone, with tunica vaginalis flap coverage alone, and with both vitamin
      C and tunica vaginalis flap coverage along with a control group subjected to a
      sham procedure. The second group experienced 9h of testicular torsion followed by
      the same treatment options as described for the 5h group. The oxidative stress
      and testosterone levels were measured 24h posttreatment. The Johnsen score,
      diameter of the seminiferous tubules, and thickness of the seminiferous tubule
      epithelium were recorded 30days following the treatment. RESULTS: The Johnsen
      score, diameter of the seminiferous tubules, and thickness of the seminiferous
      tubule epithelium significantly increased in the 5h testicular torsion group
      receiving treatment with vitamin C and tunica vaginalis flap coverage compared
      with the group receiving tunica vaginalis flap alone. The level of testosterone
      decreased significantly in all groups except for the 5h testicular torsion group
      receiving treatment with vitamin C and tunica vaginalis flap coverage. The MDA
      level also decreased in the group receiving treatment with vitamin C and tunica
      vaginalis flap coverage compared with the group receiving tunica vaginalis flap
      coverage alone. CONCLUSIONS: The results showed that the histological parameters
      and testosterone levels improved with the administration of vitamin C before
      tunica vaginalis flap coverage in the group experiencing 5h of torsion. This may
      be a result of the antioxidant effect of vitamin C. No advantage was observed for
      the 9h group, possibly because the dosage of vitamin C was inadequate.

PMID- 28760457
TI  - Critical evaluation of the Hirschsprung-associated enterocolitis (HAEC) score: A
      multicenter study of 116 children with Hirschsprung disease.
AB  - OBJECTIVE: To identify the optimal clinical criteria to diagnose Hirschsprung
      associated enterocolitis (HAEC) in children with Hirschsprung disease (HSCR).
      BACKGROUND: HAEC is the most common life-threatening complication in HSCR
      patients, yet the diagnostic criteria for HAEC remain unclear. The consensus
      based HAEC scoring system was not validated using patient data, thereby making
      its diagnostic accuracy uncertain. METHODS: From 2009 to 2015, consecutive
      children with HSCR underwent retrospective evaluation of their medical records,
      and questionnaire-directed parent interviews to identify treatment of suspected
      HAEC episodes and the 16 clinical criteria in the HAEC score. Logistic regression
      modeling was employed to identify criteria predicting suspected HAEC episodes.
      RESULTS: One hundred sixteen HSCR patients met inclusion criteria, 43 patients
      (37.1%) were treated for at least one suspected HAEC episode. An HAEC score of 4
      maximized the sum of sensitivity (83.7%) and specificity (98.6%) while the
      previously established cut-off score of 10 showed lower sensitivity (41.9%) with
      perfect specificity. Multivariable analysis identified four criteria utilized to
      create a new HAEC Risk score with performance characteristics similar to the HAEC
      score cutoff of 4. CONCLUSION: When using the HAEC score, a cutoff of 4 should be
      used rather than 10, which under-diagnosed patients with HAEC. Alternatively, the
      new HAEC Risk score could be employed. LEVEL OF EVIDENCE: Diagnostic Study, Level
      3.

PMID- 28760458
TI  - Clinical and sonographic predictors of adnexal torsion in pediatric and
      adolescent patients.
AB  - OBJECTIVE: To investigate the accuracy of torsion diagnosis in the pediatric and
      adolescent population. METHODS: This retrospective study included 87 patients
      <18years who presented with acute pelvic pain and were operated for suspected
      adnexal torsion from January 2009 to September 2016. RESULTS: Adnexal torsion was
      found in 53 of 87 (60.9%) cases operated for suspected torsion. The rate of
      accurate torsion diagnosis was significantly higher among pre-menarchal (21/21,
      100%) compared with post-menarchal girls (32/66, 48.5%) (p<0.001). Patients with
      torsion were more likely to report nausea or vomiting (73.6% compared with 32.3%,
      p<0.001) and had higher rates of peritoneal irritation signs on exam (15.1%
      compared with 0.0%, p=0.02). On the pre-operative ultrasound, patients with
      torsion were characterized by higher rates of enlarged ovary showing signs of
      edema (49.1% compared with 8.8%, p<0.001) and free pelvic fluid (45.3% compared
      with 17.6%, p<0.001). In post-menarchal girls without adnexal torsion, the
      leading diagnosis was hemorrhagic corpus luteum cyst (found in 18/33, 78.3%)
      cases. CONCLUSIONS: Various clinical and ultrasound findings may point to the
      correct diagnosis of torsion in the pediatric and adolescent population. However,
      none of the clinical and ultrasound characteristics are sufficient to confirm or
      disprove the pre-operative diagnosis, and young patients with the clinical
      suspicion of adnexal torsion should undergo laparoscopy. LEVEL OF EVIDENCE: Level
      II. TYPE OF STUDY: Clinical retrospective study.

PMID- 28760459
TI  - Patients' perception of their involvement in shared treatment decision making:
      Key factors in the treatment of inflammatory bowel disease.
AB  - OBJECTIVES: This study aims to characterize the relationships between the quality
      of the information given by the physician, the involvement of the patient in
      shared decision making (SDM), and outcomes in terms of satisfaction and anxiety
      pertaining to the treatment of inflammatory bowel disease (IBD). METHODS: A Web
      survey was conducted among 200 Canadian patients affected with IBD. The
      theoretical model of SDM was adjusted using path analysis. SAS software was used
      for all statistical analyses. RESULTS: The quality of the knowledge transfer
      between the physician and the patient is significantly associated with the
      components of SDM: information comprehension, patient involvement and decision
      certainty about the chosen treatment. In return, patient involvement in SDM is
      significantly associated with higher satisfaction and, as a result, lower anxiety
      as regards treatment selection. CONCLUSIONS: This study demonstrates the
      importance of involving patients in shared treatment decision making in the
      context of IBD. PRACTICE IMPLICATIONS: Understanding shared decision making may
      motivate patients to be more active in understanding the relevant information for
      treatment selection, as it is related to their level of satisfaction, anxiety and
      adherence to treatment. This relationship should encourage physicians to promote
      shared decision making.

PMID- 28760460
TI  - Different patterns of motor activity induce differential plastic changes in
      pyramidal neurons in the motor cortex of rats: A Golgi study.
AB  - Rehabilitation is a process which favors recovery after brain damage involving
      motor systems, and neural plasticity is the only real resource the brain has for
      inducing neurobiological events in order to bring about re-adaptation. Rats were
      placed on a treadmill and made to walk, in different groups, at different
      velocities and with varying degrees of inclination. Plastic changes in the spines
      of the apical and basal dendrites of fifth-layer pyramidal neurons in the motor
      cortices of the rats were detected after study with the Golgi method. Numbers of
      dendritic spines increased in the three experimental groups, and thin, mushroom,
      stubby, wide, and branched spines increased or decreased in proportion depending
      on the motor demands made of each group. Along with the numerical increase of
      spines, the present findings provide evidence that dendritic spines' geometrical
      plasticity is involved in the differential performance of motor activity.

PMID- 28760461
TI  - Effect of dead space on breathing stability at exercise in hypoxia.
AB  - Recent studies have shown that normal subjects exhibit periodic breathing when
      submitted to concomitant environmental (hypoxia) and physiological (exercise)
      stresses. A mathematical model including mass balance equations confirmed the
      short period of ventilatory oscillations and pointed out an important role of
      dead space in the genesis of these phenomena. Ten healthy subjects performed mild
      exercise on a cycloergometer in different conditions: rest/exercise,
      normoxia/hypoxia and no added dead space/added dead space (aDS). Ventilatory
      oscillations (VE peak power) were augmented by exercise, hypoxia and aDS
      (P<0.001, P<0.001 and P<0.01, respectively) whereas VE period was only shortened
      by exercise (P<0.001), with an 11-s period. aDS also increased VE (P<0.001),
      tidal volume (VT, P<0.001), and slightly augmented PETCO2 (P<0.05) and the
      respiratory frequency (P<0.05). These results confirmed our previous model,
      showing an exacerbation of breathing instability by increasing dead space. This
      underlines opposite effects observed in heart failure patients and normal
      subjects, in which added dead space drastically reduced periodic breathing and
      sleep apneas. It also points out that alveolar ventilation remains very close to
      metabolic needs and is not affected by an added dead space. Clinical Trial reg. n
      degrees : NCT02201875.

PMID- 28760462
TI  - Histone Modification Is Correlated With Reverse Left Ventricular Remodeling in
      Nonischemic Dilated Cardiomyopathy.
AB  - BACKGROUND: Although implantation of a left ventricular assist device (LVAD)
      induces reverse remodeling of the left ventricle in end-stage nonischemic dilated
      cardiomyopathy (DCM), the underlying mechanism is not fully understood. It has
      been shown that epigenetic modification, such as methylation or acetylation of
      the histone, is one of the most important upstream signals in cardiac failure.
      This study hypothesized that histone profiles may be modified by LVAD
      implantation for end-stage nonischemic DCM, in association with reverse left
      ventricular remodeling. METHODS: Hemodynamic changes associated with histone
      modification profiles in the left ventricle were comprehensively assessed in 14
      patients with a diagnosis of end-stage nonischemic DCM. These patients underwent
      LVAD implantation and subsequent cardiac transplantation in our institution
      (Osaka University Hospital, Osaka, Japan). Samples of normal left ventricle from
      3 different people were used as a control. RESULTS: After LVAD support for 2.5 +/
      1.2 years, the study cohort showed a significant reverse remodeling of left
      ventricular function associated with histopathologic changes in the left
      ventricle, such as reduction of myocyte size. Although the left ventricle of the
      cohort histologically expressed less 3 histone methylation-related molecules (eg,
      H3 lysine 4 trimethylation [H3K4me3], H3 lysine 9 dimethylation [H3K9me2], and H3
      lysine 9 trimethylation [H3K9me3]) compared with normal left ventricle, LVAD
      support reversed expression of these molecules, associated with up-regulation of
      H3 lysine 9 [H3K9] methyltransferase and suppressor of variegation 3-9 homologue
      1 [SUV39H1] and with down-regulation of H3K9 demethylase and jumonji domains
      [JMJDs] in the LVAD-supported left ventricle. Moreover, expression of atrial
      natriuretic peptide and brain natriuretic peptide (ANP and BNP) was negatively
      correlated with that of H3K9me2 and H3K9me3. CONCLUSIONS: The epigenetic state of
      cardiac myocytes (eg, as histone methylation) was substantially modulated in end
      stage nonischemic DCM. LVAD support partially reversed the epigenetic state and
      its upstream signals, in association with pathologic and functional reverse
      remodeling.

PMID- 28760463
TI  - Survival After Esophagectomy: A Propensity-Matched Study of Different Surgical
      Approaches.
AB  - BACKGROUND: Although open esophagectomy (OE) is considered the "gold standard"
      treatment for esophageal cancer, robotic-assisted minimally invasive
      esophagectomy (RAMIE), and laparoscopic/thoracoscopic minimally invasive
      esophagectomy (MIE) are becoming more common. This study aimed to compare short
      term outcomes and overall survival of patients undergoing RAMIE, MIE, and OE.
      METHODS: The National Cancer Data Base was queried for patients who had OE,
      RAMIE, or MIE for esophageal cancer from 2010 to 2013. Three propensity-matched
      cohorts were generated, one for each surgical approach. Survival was examined in
      the unmatched and matched cohorts. RESULTS: We identified 9,217 patients who
      underwent RAMIE (581; 6.3%), MIE (2,379; 25.8%), or OE (6,257; 67.9%). In the
      unmatched cohort, 30-day mortality was higher after RAMIE. The RAMIE and MIE
      patients had more lymph nodes harvested than OE patients. Median survival was 48
      months after RAMIE, 44 months after MIE, and 41 months after OE (p = 0.121). The
      propensity-matched groups contained 569 patients each. There was a trend toward
      higher 30-day mortality in the RAMIE group. The number of lymph nodes harvested
      was similar among the groups. There were no significant differences in survival,
      with a median survival of 48 months after RAMIE, 49 months after MIE, and 44
      months after OE (p = 0.53). CONCLUSIONS: We were unable to find significant
      differences in long-term survival of patients with esophageal cancer undergoing
      RAMIE, OE, or MIE. Surgeon experience and expertise may be more important than
      surgical approach for esophageal cancer.

PMID- 28760464
TI  - Low Accuracy of Computed Tomography and Positron Emission Tomography to Detect
      Lung and Lymph Node Metastases of Colorectal Cancer.
AB  - BACKGROUND: Minimally invasive surgery, stereotactic radiotherapy, and
      radiofrequency ablation are commonly proposed in the case of pulmonary colorectal
      metastasis as alternatives to conventional open surgery. Preoperative imaging
      assessment by computed tomography (CT) scan and fluorodeoxyglucose positron
      emission tomography (FDG-PET) are critical to guide oncologic radical treatment.
      Our aim was to investigate the accuracy of CT and FDG-PET for the evaluation of
      the number of pulmonary colorectal metastases and thoracic lymph nodal
      involvement (LNI). METHODS: Patients who underwent lung surgical resection for
      pulmonary colorectal metastases from 2004 to 2014 were analyzed. Concordance
      between histology, CT scan, and FDG-PET findings were assessed. RESULTS: Data of
      521 patients were analyzed. Of those, FDG-PET was performed in 435 (83.5%). A
      moderate agreement between both CT scan (kappa index: 0.42) and FDG-PET (kappa
      index: 0.42) findings and the histologically proven number of metastases was
      observed. The number of histologically proven metastases was correctly
      discriminated in 61.7% of cases with CT scan and in 61.8% of cases with FDG-PET.
      Multiple metastases were discovered in 20.9% of clinical single metastasis cases
      with CT scan, and in 24.4% of those cases with FDG-PET. One hundred fifty
      patients (29.1%) presented with pathologic LNI. A poor agreement was observed
      between LNI and CT scan findings (kappa index: 0.02), and a weak agreement was
      observed concerning LNI and FDG-PET findings (kappa index: 0.39). CONCLUSIONS:
      Computed tomography and FDG-PET have limitations if the objective is to detect
      all malignant nodules and to discriminate the LNI in cases of pulmonary
      metastases of colorectal cancer.

PMID- 28760466
TI  - Outcomes of Early Mitral Valve Reoperation in the Medicare Population.
AB  - BACKGROUND: Surgical series on mitral valve reoperation are limited by small
      numbers and lack of national representation. Large-scale outcomes of reoperation
      for mitral valve surgery remain uncertain. METHODS: This is a descriptive
      analysis of 1,627 Medicare beneficiaries who underwent mitral valve reoperation
      within a 3-year follow-up period after an initial mitral operation (repair or
      replacement) that took place between 2000 and 2006. The primary outcomes were
      hospital mortality and long-term survival. RESULTS: The 1,627 patients included
      in the study comprise 1.6% of patients who underwent operation between 2000 and
      2006. The initial surgery was repair in 49.9%, bioprosthetic replacement in
      22.0%, and mechanical replacement in 28.1%. Re-repair was performed in 15.4%.
      Hospital mortality was 12.0% and was similar for repair and bioprosthetic or
      mechanical replacement. Reoperative mortality was similar for men and women and
      for patients aged 75 years or less versus more than 75 years; and was
      significantly higher for nonelective than for elective operations (15.6% versus
      5.5%, p = 0.0001), for patients with endocarditis than without endocarditis
      (21.4% versus 11.0%, p = 0.0001), and for patients with heart failure than
      without heart failure (14.2% versus 9.9%, p = 0.0080). Cumulative long-term
      survival rates were 58.6% at 5 years. CONCLUSIONS: The incidence of mitral valve
      reoperation within 3 years after initial repair or replacement is low but carries
      high surgical risk, which is significantly increased by certain preoperative
      characteristics, such as urgent status, endocarditis, and heart failure.

PMID- 28760467
TI  - Resident Autonomy in the Operating Room: Expectations Versus Reality.
AB  - BACKGROUND: There is concern about graduating thoracic trainees' independent
      operative skills due to limited autonomy in training. This study compared faculty
      and trainee expected levels of autonomy with intraoperative measurements of
      autonomy for common cardiothoracic operations. METHODS: Participants underwent
      frame-of-reference training on the 4-point Zwisch scale of operative autonomy
      (show and tell -> active help -> passive help -> supervision only) and evaluated
      autonomy in actual cases using the Zwisch Me!! mobile application. A separate
      "expected autonomy" survey elicited faculty and resident perceptions of how much
      autonomy a resident should have for six common operations: decortication, wedge
      resection, thoracoscopic lobectomy, coronary artery bypass grafting, aortic valve
      replacement, and mitral valve repair. RESULTS: Thirty-three trainees from 7
      institutions submitted evaluations of 596 cases over 18 months (March 2015 to
      September 2016). Thirty attendings subsequently provided their evaluation of 476
      of those cases (79.9% response rate). Expected autonomy surveys were completed by
      21 attendings and 19 trainees from 5 institutions. The six operations included in
      the survey constituted 47% (226 of 476) of the cases evaluated. Trainee and
      attending expectations did not differ significantly for senior trainees. Both
      groups expected significantly higher levels of autonomy than observed in the
      operating room for all six types of cases. CONCLUSIONS: Although faculty and
      trainees both expect similar levels of autonomy in the operating room, real-time
      measurements of autonomy show a gap between expectations and reality. Decreasing
      this gap will require a concerted effort by both faculty and residents to focus
      on the development of independent operative skills.

PMID- 28760465
TI  - Elective Aortic Arch Repair: Factors Influencing Neurologic Outcome in 791
      Patients.
AB  - BACKGROUND: The aim of this study was to determine perioperative factors
      influencing neurologic outcome in a single-center cohort of patients undergoing
      elective aortic arch operations. METHODS: From January 2005 to June 2015, 791
      consecutive patients received open aortic arch operations with either antegrade
      selective cerebral perfusion (ASCP) (636 patients [80.4%]) or deep hypothermic
      circulatory arrest (DHCA) (155 patients [19.6%]). Main indications were
      degenerative aneurysm (85%) and chronic postdissection aneurysm (9.1%). RESULTS:
      Hospital mortality (30 days) was 5.3%. Permanent neurologic dysfunction (PND) was
      observed in 42 patients (5.3%). Significant risk factors for PND appeared to be
      femoral artery cannulation (p = 0.003), progressive cardiopulmonary bypass (p =
      0.001), circulatory arrest (p = 0.001), and ASCP time (p = 0.011). ASCP, in
      contrast to DHCA, was protective against PND (odds ratio [OR], 0.37; p = 0.003).
      Temporary neurologic dysfunction (TND) was observed in 49 patients (6.2%).
      Preoperative transient ischemic attack (TIA) (p = 0.001), progressive EuroSCORE
      (p = 0.001), left ventricular ejection fraction (LVEF) less than 50% (p = 0.003),
      and the use of femoral artery cannulation (p = 0.049) showed correlation in the
      univariate analysis. Stepwise logistic regression indicated TIA (p = 0.002; OR,
      3.24) and the EuroSCORE (p = 0.003; OR, 1.23) as independent predictors of TND.
      CONCLUSIONS: Contemporary elective aortic arch repair can be achieved with low
      mortality and a low incidence of neurologic dysfunction. ASCP was confirmed to be
      the safest method of cerebral protection. The extent of aortic arch replacement
      (apart from the frozen elephant trunk [FET] procedure) was not related to
      increased rates of TND or PND.

PMID- 28760468
TI  - Experience With Pericardiectomy for Constrictive Pericarditis Over Eight Decades.
AB  - BACKGROUND: The purpose of this study was to review the surgical outcomes of
      pericardiectomy for constrictive pericarditis and to examine risk factors for
      overall mortality in a contemporary period. METHODS: We reviewed all patients who
      underwent pericardiectomy for constriction from 1936 through 2013. The
      investigation included constrictive pericarditis cases confirmed
      intraoperatively, all other types of pericarditis were excluded; 1,071
      pericardiectomies were performed in 1,066 individual patients. Patients were
      divided into two intervals: a historical (pre-1990) group (n = 259) and a
      contemporary (1990-2013) group (n = 807). RESULTS: Patients in the contemporary
      group were older (61 versus 49 years; p < 0.001), more symptomatic (NYHA class
      III or IV in 79.6% versus 71.2%; p < 0.001), and more frequently underwent
      concomitant procedures (21.4% versus 5.4%; p < 0.001) compared with those in the
      historical group. In contrast to the historical cases in which the etiologies of
      constriction were mostly idiopathic (81.1%), nearly half of contemporary cases
      had a nonidiopathic etiology (postoperative 32.3%, radiation 11.4%). Although 30
      day mortality decreased from 13.5% in the historical era to 5.2% in the
      contemporary era (p < 0.001), overall survival was similar after adjusting for
      patient characteristics. Risk factors of overall mortality in the contemporary
      group included NYHA class III or IV (HR 2.17, p < 0.001), etiology of radiation
      (HR 3.93, p < 0.001) or postcardiac surgery (HR 1.47, p < 0.001), and need for
      cardiopulmonary bypass (HR 1.35, p = 0.014). CONCLUSIONS: There was a significant
      change in disease etiology over the study period. Long-term survival after
      pericardiectomy is affected by patient characteristics including etiology of
      constriction and severity of symptoms.

PMID- 28760469
TI  - Delayed Electroanatomic Mapping After Surgical Ablation for Persistent Atrial
      Fibrillation.
AB  - BACKGROUND: Long-term efficacy of catheter-based treatment of persistent atrial
      fibrillation is unsatisfactory. Minimally invasive surgical ablation techniques
      have been developed recently but their true efficacy has never been
      systematically tested. METHODS: Seventy patients (median age 63.5 years) with
      persistent atrial fibrillation underwent epicardial thoracoscopic radiofrequency
      pulmonary vein (PV) isolation, linear ablation, Marshal ligament disruption, and
      exclusion of the left atrial appendage. The procedure was followed by
      electroanatomic mapping 2 to 3 months later. RESULTS: Only 76% of patients were
      in sinus rhythm at the beginning of electroanatomic mapping. Right PVs were found
      isolated in a higher proportion of patients compared with left PVs (75.7% versus
      91.4%, p < 0.001). All four PVs and the left atrial posterior wall were isolated
      in 68.6% and 22.9% of patients, respectively. Most of the gaps around left PVs
      were localized in the superior and anterior quadrants, whereas in right PVs, the
      gaps were found predominantly on the roof and posterior wall. A typical site of
      reconduction on the inferior connecting line was the segment adjacent to the
      right inferior PV. No typical reconduction sites were found on the roof line, as
      58.5% of patients required completion of the roof line along its full length.
      CONCLUSIONS: Epicardial PV isolation was successful in the majority of patients,
      but was underwhelming with regard to isolation of the left PVs. Effective
      epicardially placed linear lines were rare. Our results highlight the significant
      limitations associated with a single-stage surgical approach and underline the
      necessity for a two-staged hybrid approach in the treatment of persistent atrial
      fibrillation.

PMID- 28760470
TI  - Improved Approach With Subcostal Exchange of the HeartMate II Left Ventricular
      Assist Device: Difference in On and Off Pump?
AB  - BACKGROUND: The HeartMate II (St. Jude Medical, Inc, St. Paul, MN [previously
      Thoratec]) left ventricular assist device (LVAD) exchange has traditionally
      involved a redo sternotomy. Alternate minimally invasive subcostal approaches
      have the advantage of avoiding sternal reentry, excessive bleeding, and prolonged
      recovery. METHODS: This retrospective review included patients who underwent an
      exchange from May 2009 to March 2016. The patients were divided into three
      cohorts: (1) redo sternotomy, (2) subcostal approach involving cardiopulmonary
      bypass (CPB) (ON-CPB SC), and (3) subcostal approach off the CPB pump (OFF-CPB
      SC). Data pertaining to patients' baseline characteristics and outcomes were
      collected and analyzed. RESULTS: From May 1, 2009 to July 31, 2016, 33 HeartMate
      II LVAD exchanges were performed. There were 11 redo sternotomies and 22
      subcostal exchanges, 12 of which were in the OFF-CPB SC group. There was no
      significant difference among the groups in terms of age (p = 0.75), sex (p =
      0.95), and indication for exchange (p = 0.94). There was a higher red blood cell
      transfusion requirement within the sternotomy cohort (p < 0.001). The median time
      to extubation and the intensive care unit length of stay were significantly
      shorter in the OFF-CPB SC group (1 and 2.5 days, respectively) than in the
      sternotomy (2.5 and 21 day, respectively) and ON-CPB SC groups (1.5 and 5 days,
      respectively). The 30-day and 90-day survival rates were equivalent among the
      cohorts. CONCLUSIONS: Exchange of the HeartMate II LVAD can be accomplished with
      significantly improved recovery time and transfusion requirement through a less
      invasive subcostal approach when compared with sternotomy. The subcostal approach
      can be performed safely both on and off cardiopulmonary bypass.

PMID- 28760471
TI  - Adjuvant Chemotherapy Does Not Confer Superior Survival in Patients With Atypical
      Carcinoid Tumors.
AB  - BACKGROUND: Although the use of adjuvant chemotherapy in patients with
      pathologically node-positive (pN+) atypical carcinoid tumor of the lung is an
      accepted practice, controversy exists about its use in pathologically node
      negative (pN0) patients. Our aim was to determine whether a survival advantage
      exists in patients receiving chemotherapy postoperatively for pN0 or pN+ atypical
      carcinoid tumors of the lung. METHODS: Adult patients treated with lobectomy or
      pneumonectomy for pulmonary atypical carcinoid tumor were identified using the
      National Cancer Data Base, 2006 to 2011. Propensity scoring (4:1 nearest neighbor
      algorithm) and survival analysis were used to examine the association between
      adjuvant chemotherapy and pN+ versus pN0 atypical carcinoid tumors. RESULTS: Of
      the total 581 patients identified with a diagnosis of atypical carcinoid of the
      lung, 363 (62.5%) were found to be node negative at the time of operation and 218
      (37.5%) had node-positive disease. Adjuvant chemotherapy was used in 15 patients
      (4.1%) with pN0 disease and 89 patients (40.8%) with pN+ disease. Unadjusted
      survival, at 12 and 60 months, was similar between pN+ patients who were treated
      with adjuvant chemotherapy versus patients who received operation alone (adjuvant
      chemotherapy: 98.9% at 12 months and 47.9% at 60 months versus operation alone:
      98.4% and 12 months and 67.1% at 60 months, p = 0.46) and for propensity-matched
      pN0 (adjuvant chemotherapy: 86.7% at 12 months and 73.3% at 60 months versus
      operation alone: 87.9% at 12 months and 72.3% at 60 months, p = 0.54).
      CONCLUSIONS: In a national-level analysis, the use of adjuvant chemotherapy
      postoperatively in patients with pN+ and pN0 disease conferred no survival
      advantage; further study is needed to determine proper chemotherapy use for these
      patients.

PMID- 28760472
TI  - Mitochondrial Dysfunction in Atrial Tissue of Patients Developing Postoperative
      Atrial Fibrillation.
AB  - BACKGROUND: Mitochondria are the major site of cellular oxidation. Metabolism and
      oxidative stress have been implicated as possible mechanisms for postoperative
      atrial fibrillation (POAF) after cardiac operations. Establishing the precise
      nature of mitochondrial dysfunction as an etiologic factor for oxidative stress
      related cell death and apoptosis could further the understanding of POAF. To
      establish this relationship, mitochondrial function was studied in patients
      undergoing cardiac operations that developed POAF and compared it with patients
      without POAF. METHODS: Right atrial tissue and serum samples were collected from
      85 patients before and after cardiopulmonary bypass. Microarray analysis (36
      patients) and RNA sequencing (5 patients) were performed on serum and atrial
      tissues, respectively, for identifying significantly altered genes in patients
      who developed POAF. On the basis of these results, Western blot was performed in
      52 patients for the genes that were most altered, and functional pathways were
      established. RESULTS: POAF developed in 30.6% (n = 26) of patients. Serum
      microarray showed significant fold changes in the expression of 49 genes involved
      in inflammatory response, oxidative stress, apoptosis, and amyloidosis (p < 0.05)
      in the POAF group. Similarly, RNA sequencing demonstrated an increased expression
      of genes associated with inflammatory response, fatty acid metabolism, and
      apoptosis in the POAF group (false discovery rate > 0.05). Immunoblotting showed
      a significant increase in TNFAIP6 (tumor necrosis factor, alpha-induced protein
      6; p = 0.02) and transforming growth factor-beta (p = 0.04) after cardiopulmonary
      bypass in the POAF group. There was a significant decrease in PGC-1alpha
      (peroxisome proliferator-activated receptor-gamma coactivator-1alpha; p = 0.002)
      and CPT1 (carnitine palmitoyltransferase I; p < 0.0005) in the POAF group after
      cardiopulmonary bypass. CONCLUSIONS: Compared with patients without POAF, those
      with POAF demonstrated mitochondrial dysfunction at various levels that are
      suitable for potential pharmacotherapy.

PMID- 28760473
TI  - Transapical Mitral Valve Implantation for Native Mitral Valve Stenosis Using a
      Balloon-Expandable Prosthesis.
AB  - BACKGROUND: Transcatheter mitral valve implantation (TMVI) is still in its
      infancy and is mainly limited to valve-in-valve or valve-in-ring implantations.
      We present the early experience with TMVI for severe calcified native MV
      stenosis. METHODS: Between January 2014 and June 2015, 6 of 11 patients screened
      (mean age, 77.4 +/- 6.3 years; 66% men) with severe native mitral valve (MV)
      stenosis (mean gradient [Pmean], 11.1 +/- 2.1 mm Hg; mean effective orifice area
      [EOA], 0.9 +/- 0.12 cm2) underwent transcatheter MV replacement at our
      institution as a bailout procedure. Conventional surgical procedures were denied
      in all patients because of severe annular calcification and extensive
      comorbidities (mean logistic EuroScore, 31.4% +/- 8.3%). The Edwards SAPIEN 3 (29
      mm) (Edwards Lifesciences, Irvine, CA) was used in all cases. Procedural access
      was transapical in 5 cases and concomitant to aortic valve replacement through
      the left atrium through a sternotomy in 1 case. RESULTS: Initial implantation was
      successful in 100% of the cases. Because of early migration, 1 patient needed a
      valve-in-valve procedure. Postoperative echocardiography showed no residual
      mitral regurgitation in 4 cases (66%) and mild regurgitation in 2 cases (34%).
      Mean gradients were reduced to 4.2 +/- 0.6 mm Hg (mean EOA, 2.8 +/- 0.4 cm2). No
      patient had a stroke during hospitalization, and 30-day mortality was seen in 1
      patient (17%) resulting from pneumonia. CONCLUSIONS: TMV implantation using the
      SAPIEN 3 aortic prosthesis in patients with heavy annular calcification is
      feasible and represents a reasonable bailout option for inoperable patients.
      However, several limitations need to be considered in this special patient
      population.

PMID- 28760474
TI  - Impact of Postoperative Liver Dysfunction on Survival After Left Ventricular
      Assist Device Implantation.
AB  - BACKGROUND: Liver dysfunction in left ventricular assist device (LVAD) recipients
      is common both before and after implantation. Postoperative liver dysfunction
      (PLD) develops in some LVAD recipients without preoperative liver dysfunction.
      The aim of this study was to assess clinical outcomes in such patients. METHODS:
      Records of all patients undergoing implantation of a HeartMate II (HM II, St.
      Jude Medical, Inc, Minneapolis, MN) LVAD at a single center at the University of
      Minnesota from January 2005 through June 2014 were analyzed. PLD was defined by
      hypertransaminasemia or hyperbilirubinemia, or both, during the hospitalization
      for LVAD implantation. RESULTS: During the study period, 284 patients underwent
      HM II implantation. Excluded from analysis were 14 recipients with preoperative
      liver dysfunction. In the final cohort (n = 270), there were no major difference
      in preoperative characteristics among those patients with versus without PLD. PLD
      developed in 129 (47.8%) recipients: 16 (12.4%) had isolated hypertransaminasemia
      (group I), 76 (58.9%) had isolated hyperbilirubinemia (group II), and 37 (28.7%)
      had combined hypertransaminasemia and hyperbilirubinemia (group III). Group III
      LVAD recipients had significantly greater rates of 30-day, 90-day, and 1-year
      mortality, along with significantly higher transfusion requirements and higher
      rates of renal replacement therapy, prolonged ventilation, and vasopressor use.
      Moreover, their mortality risk was significantly higher than that of PLD-free
      LVAD recipients (hazard ratio, 4.6; 95% confidence interval, 2.1 to 10.1; p <
      0.001). CONCLUSIONS: Isolated hyperbilirubinemia is common after LVAD
      implantation. In this study, it was not associated with an increase in early or
      midterm postoperative mortality. However, postoperative combined transaminasemia
      and hyperbilirubinemia was associated with a significant increase in early and
      midterm morbidity and mortality. Further research into the pathogenesis of post
      LVAD PLD is necessary.

PMID- 28760475
TI  - Cardiac Progenitor Cells Enhance Neonatal Right Ventricular Function After
      Pulmonary Artery Banding.
AB  - BACKGROUND: C-kit+ cardiac progenitor cells (CPCs) have been shown to be safe and
      effective in large-animal models and in an early-phase clinical trial for adult
      patients with ischemic heart disease. However, CPCs have not yet been evaluated
      in a preclinical model of right ventricular (RV) dysfunction, which is a salient
      feature of many forms of congenital heart disease. METHODS: Human c-kit+ CPCs
      were generated from right atrial appendage biopsy specimens obtained during
      routine congenital cardiac operations. Immunosuppressed Yorkshire swine (6 to 9
      kg) underwent pulmonary artery banding to induce RV dysfunction. Thirty minutes
      after banding, pigs received intramyocardial injection into the RV free wall with
      c-kit+ CPCs (1 million cells, n = 5) or control (phosphate-buffered saline, n =
      5). Pigs were euthanized at 30 days postbanding. RESULTS: Banding was calibrated
      to a consistent rise in the RV-to-systemic pressure ratio across both groups
      (postbanding: CPCs = 0.76 +/- 0.06, control = 0.75 +/- 0.03). At 30 days
      postbanding, the CPCs group demonstrated less RV dilatation and a significantly
      greater RV fractional area of change than the control group (p = 0.002). In
      addition, measures of RV myocardial strain, including global longitudinal strain
      and strain rate, were significantly greater in the CPCs group at 4 weeks relative
      to control (p = 0.004 and p = 0.01, respectively). The RV free wall in the CPCs
      group demonstrated increased arteriole formation (p < 0.0001) and less myocardial
      fibrosis compared with the control group (p = 0.02). CONCLUSIONS: Intramyocardial
      injection of c-kit+ CPCs results in enhanced RV performance relative to control
      at 30 days postbanding in neonatal pigs. This model is important for further
      evaluation of c-kit+ CPCs, including long-term efficacy.

PMID- 28760476
TI  - Continuous Procedural Full-Lung Ventilation During Minimally Invasive Coronary
      Bypass Grafting.
AB  - BACKGROUND: In the past, minimally invasive cardiac surgery (MICS)- coronary
      artery bypass graft surgery (CABG) alternatives have been introduced that
      dramatically reduce the invasiveness of standard operative procedures while still
      showing excellent clinical outcomes. However, in patients with high morbidity,
      reduced lung function impeding single-lung ventilation is one of the major
      concerns for MICS-CABG procedures, although those patients might reap the largest
      benefit from a procedure of reduced invasiveness. METHODS: Here, we describe a
      simple surgical technique-the fan technique-that allows for continuous full-lung
      ventilation with unimpeded surgical view during common MICS-CABG procedures. To
      evaluate the procedural feasibility of this technique, we analyzed intraoperative
      ventilation measurements of 22 consecutive MICS-CABG patients in whom the fan
      technique was used. RESULTS: This study demonstrates a significant improvement of
      standard respiratory measurements during procedural full-lung ventilation using
      the fan technique as compared with conventional single-lung ventilation
      (ventilation pressure 21.4 +/- 3.2 versus 26.6 +/- 3 mbar, p < 0.001; respiratory
      rate 13.1 +/- 1.4 versus 14.4 +/- 2.2 breaths per minute, p < 0.001; minute
      volume 7.4 +/- 1.1 versus 6.2 +/- 1 L/min, p < 0.0001; Pao2 during ventilation
      294.9 +/- 74.6 versus 153.2 +/- 71 mm Hg, p < 0.0001). CONCLUSIONS: The presented
      technique may not only enable us to perform MICS-CABG procedures in patients not
      suitable for single-lung ventilation owing to reduced pulmonary function, but
      also may soon also become a standard procedure for MICS-CABG surgery, especially
      with regard to procedures involving complex and time-consuming multivessel
      revascularizations. However, further studies are strongly warranted to assess
      whether the fan technique may also decrease postoperative pulmonary complications
      and benefit clinical outcome indicators.

PMID- 28760477
TI  - The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2017 Update
      on Research.
AB  - The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS CHSD) is
      the largest congenital and pediatric cardiac surgical clinical data registry in
      the world. It contains data pertaining to more than 435,000 total operations. The
      most recent biannual feedback report to participants (Spring 2017, Report of the
      Twenty-Sixth Harvest) included analysis of data submitted from 127 hospitals in
      North America. That represents nearly all centers performing pediatric and
      congenital heart operations in the United States and Canada. As an unparalleled
      platform for assessment of outcomes and for quality improvement activities in the
      subspecialty of surgery for pediatric and congenital heart disease, the STS CHSD
      continues to be a primary data source for clinical investigations and for
      research and innovations related to quality measurement. In 2016, several major
      original publications reported analyses of data in the CHSD pertaining to various
      processes of care, including assessment of variation across centers and
      associations between specific practices, patient characteristics, and outcomes.
      Additional publications reported the most recent development, evaluation, and
      application of metrics for quality measurement and reporting of pediatric and
      congenital heart operation outcomes and center level performance. Use of the STS
      CHSD for outcomes research and for quality measurement continues to expand as
      database participation has grown to include nearly all centers in North America,
      and the available wealth of data in the database continues to grow. This article
      reviews outcomes research and quality improvement articles published in 2016 that
      are based on STS CHSD data.

PMID- 28760478
TI  - Engaging the Senses, Understanding Publics: Research Methods, Science Engagement,
      and Synthetic Biology.
AB  - Scientists and government actors often fear a 'public rejection' of
      biotechnology, especially regarding genetic modification. Through a research
      project aimed at engaging people's senses, we support an alternative way for
      scientists to consider non-scientists in their research.

PMID- 28760479
TI  - Renal carriage of Leptospira species in rodents from Mediterranean Chile: The
      Norway rat (Rattus norvegicus) as a relevant host in agricultural lands.
AB  - We evaluated the renal carriage of Leptospira species in rodent communities from
      Mediterranean Chile using a PCR technique. We found that animals inhabiting
      agricultural areas were almost three times more infected than in wild areas
      (14.4% vs. 4.4%). The Norwegian rat (Rattus norvegicus), an invasive murid
      ubiquitous in the country, was the most infected species (38.1%).

PMID- 28760480
TI  - Seroprevalence and risk factors of glanders in working equines - Findings of a
      cross-sectional study in Punjab province of Pakistan.
AB  - Glanders is an infectious and contagious bacterial disease of equines. A little
      is known about its seroprevalence and risk factors in working equines in
      countries where the disease is endemic. Also, there are no reports on prevalence
      of the disease in areas where there is a prior evidence of Burkholderia (B.)
      mallei detection in soil. A cross-sectional study was conducted in selected
      districts (n=09) of Punjab province of Pakistan during 2014-2015. A total of 1008
      serum samples were screened for detection of antibodies to B. mallei with
      complement fixation test followed by western blot. The overall seroprevalence was
      found to be 3.17% (95% CI: 2.25-4.44). The seropositivity was significantly
      higher from the sampling sites where B. mallei was detected in soil [OR: 10.66
      (95% CI: 4.42-31.66), p=0.00]. Other risk factors significantly associated with
      animal seropositivity were: age group [OR: 1.78 (95% CI: 4.58-15.56), p=0.00],
      location in urban area [OR: 2.99 (95% CI: 1.46-6.51), p=0.00],body condition [OR:
      3.47 (95% CI: 1.64-7.99), p=0.00], presence of farcy lesion[OR: 7.71 (95% CI:
      3.47-19.50), p=0.00], proximity to water bodies [OR: 7.71 (95% CI: 3.47-19.50),
      p=0.00]; domestic animal population [OR: 3.20 (95% CI: 1.24-10.87), p=0.03] and
      number of households in sampling area [OR: 4.18 (95%CI: 1.82-11.30), p=0.00]. The
      study provides an estimate of prevalence of glanders and a potential link between
      animal seropositivity and presence of B. mallei in soil. The risk factors
      identified in this study can be used in surveillance and disease awareness. The
      high prevalence of disease in draught horses and contact of infected animals with
      their care-takers in developing countries signify need to initiate progressive
      control of the disease using one health approach.

PMID- 28760481
TI  - Molecular identification and phylogenetic analysis of human Trichostrongylus
      species from an endemic area of Iran.
AB  - Human infections with Trichostrongylus species have been reported in most parts
      of Iran. The aim of this study was the identification, molecular characterization
      and phylogenetic analysis of human Trichostrongylus species based on ITS2 region
      of ribosomal DNA from Guilan Province, northern Iran. Stool samples were
      collected from rural inhabitants and examined by formalin-ether concentration and
      agar plate culture techniques. After anthelmintic treatment, male adult worms
      were collected from five infected cases. Genomic DNA was extracted from one male
      worm of each species in every treated individual and one filariform larva
      isolated from each case. PCR amplification of ITS2-rDNA region was performed and
      the products were sequenced. Among 1508 individuals, 46 (3.05%) were found
      infected with Trichostrongylus species using parasitological methods. Male worms
      of T. colubriformis, T. vitrinus and T. longispicularis were expelled from five
      patients after treatment. Out of 41 filariform larvae, 40 were T. colubriformis,
      and the other one was T. axei. Phylogenetic analysis showed that each species was
      placed together with reference sequences submitted to GenBank database. Intra
      species similarity for all species obtained in the current study was 100%. T.
      colubriformis was found to be probably the most common species in this region of
      Iran. For the first time, the authors of the present study report the occurrence
      of natural human infection by T. longispicularis in the world. Therefore, the
      number of Trichostrongylus species infecting human in Iran now increased to ten.

PMID- 28760482
TI  - Evaluation of chemical spraying and environmental management efficacy in areas
      with minor previous application of integrated control actions for visceral
      leishmaniasis in Brazil.
AB  - Leishmaniases are vector-borne diseases that are transmitted to humans through
      the bite of Leishmania-infected phlebotomine sand flies (Diptera:Psychodidae).
      The main proved vector of visceral leishmaniais (VL) in the New World - Lutzomyia
      longipalpis - is well-adapted to urban areas and has extensive distribution
      within the five geographical regions of Brazil. Integrated public health actions
      directed for the vector, domestic reservoir and humans for the control of VL are
      preferentially applied in municipalities with higher epidemiological risk of
      transmission. In this study, we evaluated the individual impact of two main
      vector control actions - chemical spraying and environmental management - in two
      districts with no reported cases of human VL. Although belonging to an endemic
      municipality for VL in Brazil, the integrated control actions have not been
      applied in these districts due to the absence of human cases. The number of L.
      longipalpis captured in a two-year period was used as indicator of the population
      density of the vector. After chemical spraying a tendency of reduction in L.
      longipalpis was observed but with no statistical significance compared to the
      control. Environmental management was effective in that reduction and it may help
      in the control of VL by reducing the population density of the vector in a
      preventive and more permanent action, perhaps associated with chemical spraying.

PMID- 28760483
TI  - Preliminary efficacy investigations of oral fipronil against Anopheles arabiensis
      when administered to Zebu cattle (Bos indicus) under field conditions.
AB  - Globally, malaria remains one of the most important vector-borne diseases despite
      the extensive use of vector control, including indoor residual spraying (IRS) and
      insecticide-treated nets (ITNs). These control methods target endophagic vectors,
      whereas some malaria vectors, such as Anopheles arabiensis, preferentially feed
      outdoors on cattle, making it a complicated vector to control using conventional
      strategies. Our study evaluated whether treating cattle with a capsule containing
      the active ingredient (AI) fipronil could reduce vector density and sporozoite
      rates, and alter blood feeding behavior, when applied in a small-scale field
      study. A pilot field study was carried out in the Samia District, Western Kenya,
      from May to July 2015. Four plots, each comprised of 50 huts used for sleeping,
      were randomly designated to serve as control or treatment. A week before cattle
      treatment, baseline mosquito collections were performed inside the houses using
      mechanical aspirators. Animals in the treatment (and buffer) were administered a
      single oral application of fipronil at ~0.5mg/kg of body weight. Indoor mosquito
      collections were performed once a week for four weeks following treatment. Female
      mosquitoes were first identified morphologically to species complex, followed by
      PCR-based methods to obtain species identity, sporozoite presence, and the host
      source of the blood meal. All three species of anophelines found in the study
      area (An. gambiae s.s., An. arabiensis, An. funestus s.s.) were actively
      transmitting Plasmodium falciparum during the study period. The indoor resting
      density of An. arabiensis was significantly reduced in treatment plot one at
      three weeks post-treatment (T1) (efficacy=89%; T1 density=0.08, 95% credibility
      intervals [0.05, 0.10]; control plot density=0.78 [0.22, 0.29]) and at four weeks
      post-treatment (efficacy=64%; T1 density=0.16 [0.08, 0.14]; control plot
      density=0.48 [0.17, 0.22]). The reduction of An. arabiensis mosquitoes captured
      in the treatment plot two was higher: zero females were collected after
      treatment. The indoor resting density of An. gambiae s.s. was not significantly
      different between the treatment (T1, T2) and their corresponding control plots
      (C1, C2). An. funestus s.s. showed an increase in density over time. The results
      of this preliminary study suggest that treating cattle orally with fipronil, to
      target exophagic and zoophagic malaria vectors, could be a valuable control
      strategy to supplement existing vector control interventions which target
      endophilic anthropophilic species.

PMID- 28760484
TI  - Pulsed-dose rate brachytherapy for pediatric bladder prostate rhabdomyosarcoma:
      Compliance and early clinical results.
AB  - OBJECTIVE: No data are available on the feasibility of pulsed dose rate (PDR)
      brachytherapy in very young children. Our experience of PDR brachytherapy for
      bladder prostate (BP) rhabdomyosarcoma (RMS) is reported, with focus on
      compliance and dosimetric parameters. MATERIALS AND METHODS: Treatment parameters
      and outcome of consecutive BP RMS patients treated in our center were examined.
      Treatment was carried out as part of a multimodal conservative radio-surgical
      treatment. Four single leader plastic tubes were implanted under perioperative
      guidance, encompassing the prostate/bladder neck. Tubes were systematically
      sutured to the bladder wall. Treatment planning was based on a computed
      tomography and followed Paris system rules. Continuous hourly pulses of 0.42Gy
      were delivered, to a total dose of 60Gy. RESULTS: 32 patients were treated,
      median age 2.6years (10months-12years). Median duration of each pulse was 8.5min
      (3.8-17.4min). The minimal dose in the most irradiated 1cm3 of rectum was
      44.7Gyalpha/beta=3 (range: 4.1-77.3Gyalpha/beta=3). Brachytherapy was conducted
      without significant compliance concern in all but two patients, 24 and 25months
      old, who pulled out plastic tubes before treatment completion. Another child
      needed re-planning because of slight tube displacement. With median follow-up of
      14.4months (15days-75months), all patients were free from any relapse after local
      treatment. Four grade 3 acute urinary complications were encountered. All long
      term side effects were grade 2 or less. CONCLUSION: PDR brachytherapy is feasible
      in very young patients, and associated with acceptable acute toxicity rates.
      Longer follow-up is required to ensure that local control and long-term side
      effects profile are comparable to the results of low dose rate brachytherapy.

PMID- 28760485
TI  - Phospholipid class-specific brain enrichment in response to
      lysophosphatidylcholine docosahexaenoic acid infusion.
AB  - Recent studies suggest that at least two pools of plasma docosahexaenoic acid
      (DHA) can supply the brain: non-esterified DHA (NE-DHA) and
      lysophosphatidylcholine (lysoPtdCho)-DHA. In contrast to NE-DHA, brain uptake of
      lysoPtdCho-DHA appears to be mediated by a specific transporter, but whether both
      forms of DHA supply undergo the same metabolic fate, particularly with regards to
      enrichment of specific phospholipid (PL) subclasses, remains to be determined.
      This study aimed to evaluate brain uptake of NE-DHA and lysoPtdCho-DHA into brain
      PL classes. Fifteen-week-old rats were infused intravenously with radiolabelled
      NE-14C-DHA or lysoPtdCho-14C-DHA (n=4/group) over five mins to achieve a steady
      state plasma level. PLs were extracted from the brain and separated by thin layer
      chromatography and radioactivity was quantified by liquid scintillation counting.
      The net rate of entry of lysoPtdCho-DHA into the brain was between 59% and 86%
      lower than the net rate of entry of NE-DHA, depending on the PL class. The
      proportion of total PL radioactivity in the lysoPtdCho-14C-DHA group compared to
      the NE-14C-DHA group was significantly higher in choline glycerophospholipids
      (ChoGpl) (48% vs 28%, respectively) but lower in ethanolamine
      glycerophospholipids (EtnGpl) (32% vs 46%, respectively). In both groups,
      radioactivity was disproportionally high in phosphatidylinositol and ChoGpl but
      low in phosphatidylserine and EtnGpl compared to the corresponding DHA pool size.
      This suggests that DHA undergoes extensive PL remodeling after entry into the
      brain.

PMID- 28760486
TI  - A novel Brain Computer Interface for classification of social joint attention in
      autism and comparison of 3 experimental setups: A feasibility study.
AB  - BACKGROUND: We present a novel virtual-reality P300-based Brain Computer
      Interface (BCI) paradigm using social cues to direct the focus of attention. We
      combined interactive immersive virtual-reality (VR) technology with the
      properties of P300 signals in a training tool which can be used in social
      attention disorders such as autism spectrum disorder (ASD). NEW METHOD: We tested
      the novel social attention training paradigm (P300-based BCI paradigm for
      rehabilitation of joint-attention skills) in 13 healthy participants, in 3 EEG
      systems. The more suitable setup was tested online with 4 ASD subjects.
      Statistical accuracy was assessed based on the detection of P300, using spatial
      filtering and a Naive-Bayes classifier. RESULTS: We compared: 1 - g.Mobilab+
      (active dry-electrodes, wireless transmission); 2 - g.Nautilus (active
      electrodes, wireless transmission); 3 - V-Amp with actiCAP Xpress dry-electrodes.
      Significant statistical classification was achieved in all systems. g.Nautilus
      proved to be the best performing system in terms of accuracy in the detection of
      P300, preparation time, speed and reported comfort. Proof of concept tests in ASD
      participants proved that this setup is feasible for training joint attention
      skills in ASD. COMPARISON WITH EXISTING METHODS: This work provides a unique
      combination of 'easy-to-use' BCI systems with new technologies such as VR to
      train joint-attention skills in autism. CONCLUSIONS: Our P300 BCI paradigm is
      feasible for future Phase I/II clinical trials to train joint-attention skills,
      with successful classification within few trials, online in ASD participants. The
      g.Nautilus system is the best performing one to use with the developed BCI setup.

PMID- 28760487
TI  - Complications of therapeutic apheresis in pediatric kidney transplantation.
AB  - In the setting of kidney transplantation, therapeutic apheresis (TA) is employed
      both for pre-intervention procedures and during the post-transplant period. In
      pediatric nephrology units, TA is usually performed as a therapeutic plasma
      exchange (TPE) with dialysis equipment, and using non-plasma replacement fluids.
      In children undergoing kidney transplantation, complications of TPE are mainly
      related to its depletive properties combined with the iatrogenic immunodeficiency
      status of the patient. Moreover, the use of small central venous catheters and
      the equipment standardized for adults can increase the risk of adverse events.
      Focusing on these preconditions, TA in kidney-transplanted children should be
      performed in specialized centers with specific protocols and a trained staff.

PMID- 28760488
TI  - Genetically Engineered Bacteria for Treating Human Disease.
AB  - Bacteria have now been harnessed to combat human diseases, especially to meet the
      challenge of antimicrobial resistance. Modulating the microbiome, particularly by
      genetically engineering the bacteria, has provided proof-of-concept as potential
      pharmacotherapy, but those involved in this field should engage in discussion as
      how to move forward.

PMID- 28760489
TI  - MDR in cancer: Addressing the underlying cellular alterations with the use of
      nanocarriers.
AB  - Multidrug resistance (MDR) is associated with a wide range of pathological
      changes at different cellular and intracellular levels. Nanoparticles (NPs) have
      been extensively exploited as the carriers of MDR reversing payloads to resistant
      tumor cells. However, when properly formulated in terms of chemical composition
      and physicochemical properties, NPs can serve as beyond delivery systems and help
      overcome MDR even without carrying a load of chemosensitizers or MDR reversing
      molecular cargos. Whether serving as drug carriers or beyond, a wise design of
      the nanoparticulate systems to overcome the cellular and intracellular
      alterations underlying the resistance is imperative. Within the current review,
      we will initially discuss the cellular changes occurring in resistant cells and
      how such changes lead to chemotherapy failure and cancer cell survival. We will
      then focus on different mechanisms through which nanosystems with appropriate
      chemical composition and physicochemical properties can serve as MDR reversing
      units at different cellular and intracellular levels according to the changes
      that underlie the resistance. Finally, we will conclude by discussing logical
      grounds for a wise and rational design of MDR reversing nanoparticulate systems
      to improve the cancer therapeutic approaches.

PMID- 28760490
TI  - beta3 adrenergic receptor activation relaxes human corpus cavernosum and penile
      artery through a hydrogen sulfide/cGMP-dependent mechanism.
AB  - Erectile function is a widely accepted indicator of systemic endothelial activity
      since from a clinical standpoint erectile dysfunction (ED) often precedes
      cardiovascular events. Recently it has been described a potential role for beta3
      adrenoceptor in cardiovascular diseases emphasizing a possible development of new
      drugs. beta3 adrenoceptor stimulation relaxes human corpus cavernosum (HCC)
      strips in cyclic guanosine monophosphate (cGMP)-dependent and endothelium/nitric
      oxide (NO)-independent manner. Hydrogen sulfide (H2S), along with NO, is another
      gaseous molecule involved in cardiovascular system and as a consequence also in
      penile erection. Cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase
      (CSE), the enzymes mainly responsible for H2S biosynthesis, are constitutively
      expressed in HCC. CSE rather than CBS is more abundant in human penile tissue.
      Herein we investigated the involvement of H2S pathway in beta3 adrenoceptor
      induced relaxation in HCC and penile artery. Penile artery expresses both CSE and
      beta3 adrenoceptor. BRL37344, a beta3 selective agonist, relaxed HCC strips and
      penile artery rings and this effect was significantly reduced by CSE inhibition.
      Incubation of HCC and penile artery homogenate with BRL37344 significantly
      increased H2S production. This effect was significantly reduced by the inhibition
      of either CSE or beta3 adrenoceptor. Finally, the BRL37344-induced increase in
      cGMP was reduced by CSE inhibition in both tissues. Thus, BRL37344-induced
      relaxation in HCC and penile artery occurs in a H2S/cGMP-dependent manner. In
      conclusion, beta3/H2S/cGMP pathway can act as an alternative to NO. Since about
      15% of patients do not respond to phosphodiesterase-5 inhibitors, beta3 agonists
      could represent a therapeutic alternative or a useful adjuvant therapy to treat
      these patients.

PMID- 28760491
TI  - Effects of tibolone on fibrinogen and antithrombin III: A systematic review and
      meta-analysis of controlled trials.
AB  - Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic
      activity, but the evidence regarding its effects on fibrinogen and antithrombin
      III (ATIII) has not been conclusive. We assessed the impact of tibolone on
      fibrinogen and ATIII through a systematic review and meta-analysis of available
      randomized controlled trials (RCTs). The search included PUBMED, Web of Science,
      Scopus, and Google Scholar (up to January 31st, 2016) to identify controlled
      clinical studies investigating the effects of oral tibolone treatment on
      fibrinogen and ATIII. Overall, the impact of tibolone on plasma fibrinogen
      concentrations was reported in 10 trials comprising 11 treatment arms. Meta
      analysis did not suggest a significant reduction of fibrinogen levels following
      treatment with tibolone (WMD: -5.38%, 95% CI: -11.92, +1.16, p=0.107). This
      result was robust in the sensitivity analysis and not influenced after omitting
      each of the included studies from meta-analysis. When the studies were
      categorized according to the duration of treatment, there was no effect in the
      subsets of trials lasting either <12months (WMD: -7.64%, 95% CI: -16.58, +1.29,
      p=0.094) or >=12months (WMD: -0.62%, 95% CI: -8.40, +7.17, p=0.876). With regard
      to ATIII, there was no change following treatment with tibolone (WMD: +0.74%, 95%
      CI: -1.44, +2.93, p=0.505) and this effect was robust in sensitivity analysis.
      There was no differential effect of tibolone on plasma ATIII concentrations in
      trials with either <12months (WMD: +2.26%, 95% CI: -3.14, +7.66, p=0.411)
      or>=12months (WMD: +0.06%, 95% CI: -1.16, +1.28, p=0.926) duration. Consistent
      with the results of subgroup analysis, meta-regression did not suggest any
      significant association between the changes in plasma concentrations of
      fibrinogen (slope: +0.40; 95% CI: -0.39, +1.19; p=0.317) and ATIII (slope: -0.17;
      95% CI: -0.54, +0.20; p=0.374) with duration of treatment. In conclusion, meta
      analysis did not suggest a significant reduction of fibrinogen and ATIII levels
      following treatment with tibolone.

PMID- 28760492
TI  - Achieving Extended Longevity and Quality of Life for Senior Patients With
      Hypertrophic Cardiomyopathy: What Is Possible.

PMID- 28760493
TI  - Morphology based scoring of chromosomal instability and its correlation with cell
      viability.
AB  - OBJECTIVE: The aim of this study was to devise the quantitative scoring system
      for Chromosomal instability (CIN) based on morphological indicators like MPM, NB,
      NPB, CS, La and MN in cancer cell line and to correlate it with cell viability
      and death. METHODS: Human hepatocellular carcinoma (HepG2) cells were treated
      with drugs like Diethylstilbestrol 0-100MUM, Griseofulvin 0-40MUg/ml, Vincristine
      sulphate 0-25MUg/ml, Mitomycin C 0-600ng/ml, Bleomycin 0-10MUg/ml, Doxorubicin 0
      30MUg/ml for 24h. Following this, the CIN was assessed by counting the
      morphological indicators like Micronuclei (MN), Nuclear Buds (NB), Nucleoplasmic
      bridges, Laggards, Multipolar mitosis and chromatin strings/1000 cells in Giemsa
      stained smears by light microscopy and by determining the percentage of aneuploid
      cells by flow cytometry. The cell viability was assessed by MTT assay and
      percentage of apoptotic cells was determined by flow cytometry. RESULTS: The MN
      and NB were most frequently seen indicators and main determinants of
      morphological CIN. However, the morphological CIN score did not show any
      correlation with cell viability and apoptosis. Aneuploidy however was found to
      correlate positively with cell viability and NB score in our study (P-value
      <0.05). CONCLUSIONS: The study for the 1st time attempted to develop a scoring
      system for CIN based on morphological parameters. However, a no correlation was
      observed between the later and cell viability or apoptosis. More robust
      techniques to quantify CIN may perhaps be more helpful in exploring the true link
      between CIN and cell viability in future.

PMID- 28760494
TI  - Trefoil factor family 1 expression in the invasion front is a poor prognostic
      factor associated with lymph node metastasis in pancreatic cancer.
AB  - OBJECTIVES: Trefoil Factor Family protein 1 (TFF1) is secreted from mucus
      producing cells. The relationship between TFF1 expression and clinical outcome in
      pancreatic ductal adenocarcinoma (PDAC) remains unknown. We aimed to evaluate the
      prognostic significance of TFF1 expression in PDAC. METHODS: TFF1 expression was
      examined on paraffin-embedded sections from 91 patients with resected PDAC using
      immunohistochemistry. The relationships between TFF1 expression and
      clinicopathological features were analyzed. RESULTS: Among 91 PDAC patients, 71
      patients (79.7%) showed TFF1 expression in cancer cells. In a subgroup of 71
      patients, TFF1 expression was predominantly observed in the central part of the
      tumor, whereas TFF1 expression in the invasion front was reduced in 33 patients
      (46.4%). A significant correlation between preserved TFF1 expression in the
      invasion front and lymph node metastasis was observed. Univariate survival
      analysis revealed that preserved TFF1 expression in the invasion front, positive
      lymphatic invasion, lymph node metastasis and R1 resection was a significant poor
      prognostic factor in TFF1-positive PDAC patients. CONCLUSIONS: TFF1 expression is
      frequently lost or decreased in the invasion front of human PDAC, and preserved
      TFF1 expression in the invasion front might predict poor survival in patients
      with PDAC.

PMID- 28760495
TI  - Incidence and risk of acute coronary syndrome in patients with acute
      pancreatitis: A nationwide cohort study.
AB  - BACKGROUND: Studies on the relationship between acute pancreatitis (AP) and acute
      coronary syndrome (ACS) are scant. We conducted a nationwide cohort study to
      investigate the incidence and risk of ACS in patients with AP. METHODS: We
      enrolled patients newly diagnosed with AP between 2000 and 2010 from the Taiwan
      National Health Insurance Research Database and randomly selected a control
      cohort without a history of AP after frequency-matching for age, sex, and index
      year at a ratio of 4:1 for each patient with AP. The follow-up period was from
      the index date of new AP diagnosis to the diagnosis of ACS, censoring, or the end
      of 2011. RESULTS: We assessed 87 068 patients in the AP cohort and 348 272
      participants in the control cohort for 508 991 and 2 301 317 person-years,
      respectively. The AP cohort exhibited a higher overall incidence of ACS than the
      control cohort (5.44 vs 3.03 per 1000 person-y). After adjustment for sex, age,
      and comorbidities, the AP cohort exhibited a 1.24-fold higher adjusted hazard
      ratio (aHR) of ACS (95% confidence interval = 1.19-1.30) than did the control
      cohort. When stratified by age, the patients with AP aged <=39 years presented a
      2.37-fold higher aHR of ACS than did their corresponding controls (95% CI = 1.88
      2.99). Approximate one third of ACS developed within 1 month of AP occurrence.
      CONCLUSIONS: This nationwide cohort study indicated that patients with AP are at
      an increased risk of ACS compared with those without AP.

PMID- 28760496
TI  - Pigeon interaction mode switch-based UAV distributed flocking control under
      obstacle environments.
AB  - Unmanned aerial vehicle (UAV) flocking control is a serious and challenging
      problem due to local interactions and changing environments. In this paper, a
      pigeon flocking model and a pigeon coordinated obstacle-avoiding model are
      proposed based on a behavior that pigeon flocks will switch between hierarchical
      and egalitarian interaction mode at different flight phases. Owning to the
      similarity between bird flocks and UAV swarms in essence, a distributed flocking
      control algorithm based on the proposed pigeon flocking and coordinated obstacle
      avoiding models is designed to coordinate a heterogeneous UAV swarm to fly though
      obstacle environments with few informed individuals. The comparative simulation
      results are elaborated to show the feasibility, validity and superiority of our
      proposed algorithm.

PMID- 28760497
TI  - Robust adaptive precision motion control of hydraulic actuators with valve dead
      zone compensation.
AB  - This paper addresses the high performance motion control of hydraulic actuators
      with parametric uncertainties, unmodeled disturbances and unknown valve dead
      zone. By constructing a smooth dead-zone inverse, a robust adaptive controller is
      proposed via backstepping method, in which adaptive law is synthesized to deal
      with parametric uncertainties and a continuous nonlinear robust control law to
      suppress unmodeled disturbances. Since the unknown dead-zone parameters can be
      estimated by adaptive law and then the effect of dead-zone can be compensated
      effectively via inverse operation, improved tracking performance can be expected.
      In addition, the disturbance upper bounds can also be updated online by adaptive
      laws, which increases the controller operability in practice. The Lyapunov based
      stability analysis shows that excellent asymptotic output tracking with zero
      steady-state error can be achieved by the developed controller even in the
      presence of unmodeled disturbance and unknown valve dead-zone. Finally, the
      proposed control strategy is experimentally tested on a servovalve controlled
      hydraulic actuation system subjected to an artificial valve dead-zone.
      Comparative experimental results are obtained to illustrate the effectiveness of
      the proposed control scheme.

PMID- 28760498
TI  - Differences and similarities between sublingual immunotherapy of allergy and oral
      tolerance.
AB  - Allergen immunotherapy is the only treatment altering the natural course of IgE
      mediated allergies. Whereas the subcutaneous route for immunotherapy (SCIT) has
      been historically considered as a reference, we discuss herein the relative
      advantages of the sublingual and oral routes as alternatives to SCIT in order to
      elicit allergen-specific tolerance. The buccal and gut immune systems are
      similarly organized to favor immune tolerance to antigens/allergens, due to the
      presence of tolerogenic dendritic cells and macrophages promoting the
      differentiation of CD4+ regulatory T cells. Sublingual immunotherapy (SLIT) is
      now established as a valid treatment option, with clinical efficacy demonstrated
      in allergic rhinoconjunctivitis (to either grass, tree, weed pollens or mite
      allergens) and encouraging results obtained in the management of mild/moderate
      allergic asthma. While still exploratory, oral immunotherapy (OIT) has shown
      promising results in the desensitization of patients with food allergies. We
      review at both biological and clinical levels the perspectives currently pursued
      for those two mucosal routes.

PMID- 28760499
TI  - Nanoparticles and targeted drug delivery in cancer therapy.
AB  - Surgery, chemotherapy, radiotherapy, and hormone therapy are the main common anti
      tumor therapeutic approaches. However, the non-specific targeting of cancer cells
      has made these approaches non-effective in the significant number of patients.
      Non-specific targeting of malignant cells also makes indispensable the
      application of the higher doses of drugs to reach the tumor region. Therefore,
      there are two main barriers in the way to reach the tumor area with maximum
      efficacy. The first, inhibition of drug delivery to healthy non-cancer cells and
      the second, the direct conduction of drugs into tumor site. Nanoparticles (NPs)
      are the new identified tools by which we can deliver drugs into tumor cells with
      minimum drug leakage into normal cells. Conjugation of NPs with ligands of cancer
      specific tumor biomarkers is a potent therapeutic approach to treat cancer
      diseases with the high efficacy. It has been shown that conjugation of
      nanocarriers with molecules such as antibodies and their variable fragments,
      peptides, nucleic aptamers, vitamins, and carbohydrates can lead to effective
      targeted drug delivery to cancer cells and thereby cancer attenuation. In this
      review, we will discuss on the efficacy of the different targeting approaches
      used for targeted drug delivery to malignant cells by NPs.

PMID- 28760500
TI  - Status of Resident Attrition From Surgical Residency in the Past, Present, and
      Future Outlook.
AB  - OBJECTIVE: To investigate the current rate of attrition in general surgery
      residency, assess the risk factors, and identify prevention strategies. DESIGN: A
      literature review of the PubMed and MEDLINE databases, from January 1, 1980 to
      February 1, 2016, for relevant articles. The calculated attrition rate and the
      statistically significant influencing factors were the main measures and
      outcomes. SELECTION: All English language articles that described attrition from
      a general surgery residency were included. Articles that performed an assessment
      of attrition rates, academic performance, reasons for resident loss, and
      demographics were identified and data from these studies were collected. Random
      effect meta-analysis and meta-regression based on a generalized mixed-effects
      model was performed. RESULTS: A total of 26 studies were included. Reported
      attrition rates ranged from 2% to 30% over the course of residency training.
      Random-effect meta-analysis is indicative of a yearly attrition rate of 2.4% (95%
      CI: 1.3%-3.5%) and a cumulative 5-year attrition rate of 12.9% (95% CI: 7.9%
      17.8%). Most of them leave residency during their first 2 years, and the rate
      significantly decreases with increasing postgraduate year (p < 0.0001). The
      Accreditation Council for Graduate Medical Education mandated 80-hour week is
      associated with a higher rate, though not significantly (3.2% [95% CI: 1.3%-5.1%]
      vs. 2.2% [0.9%-3.5%], p = 0.37). Pooled analysis demonstrates no statistically
      significant difference in the rate of attrition between males and females (2.1%
      [95% CI: 1.1%-3%] vs. 2.9% [95% CI: 1.6%-4.1%], p = 0.73). Most remain in
      graduate medical education and pursue residency training in other specialties.
      CONCLUSION: Attrition in general surgery most commonly occurs within the first 2
      years of training and, in contrast to previous findings, is not related to female
      sex. Restrictions on work hours seem to have increased the rate, whereas
      remediation practices can prevent it. Training programs should direct efforts
      towards attrition-prevention strategies.

PMID- 28760501
TI  - [Hypersensitivity to platinum salts and taxanes: The value of skin tests and
      tolerance induction procedures].
AB  - AIM: The rate of hypersensitivity reactions to platinum salts (PS) and taxanes
      (TX) is on the increase. The aim of our study was to show the value of skin
      testing and efficacy of rapid drug desensitization. PATIENTS AND METHODS: This
      was a retrospective study conducted between January 2007 and February 2016 in
      patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin
      prick tests (pT) and intradermal reaction tests (IDR) were performed according to
      the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for
      rapid drug desensitization. RESULTS: Among the 99 patients included (30 men, 69
      women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin
      tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2
      for taxanes. Rapid drug desensitization was proposed in 50 patients and performed
      in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation
      being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for
      the latter 4 patients were positive. Seventy-five percent of patients with
      positive skin tests to oxaliplatin presented hypersensitivity reactions during
      desensitization, i.e. twice as many as patients having negative skin tests. Two
      percent of patient for PS and 7% for TX had cross reactivity. CONCLUSION: This
      French study confirms the efficacy of the 12-step protocol that allows patients
      to receive chemotherapy after hypersensitivity reaction. Skin test permits the
      detection of cross-reactions but their practice must be considered based on the
      patient's history.

PMID- 28760502
TI  - [Extensive connective tissue nevus in children].
AB  - BACKGROUND: Connective tissue nevus (CTN) is a rare condition of the
      extracellular matrix components that generally presents as papulae of normal skin
      colour. This condition may be syndromic or sporadic. PATIENTS AND METHODS: We
      report herein two isolated cases of extensive and infiltrative CTN in children at
      risk for subsequent joint stiffening. The pathology samples displayed
      respectively mixed hamartoma and a collagenoma. DISCUSSION: The onset of these
      lesions is often difficult to establish, since they are usually unnoticeable at
      first. When confronted with extensive CTN, the main differential diagnoses are
      eosinophilic fasciitis and morphea, and these must be ruled out by skin biopsy.
      CTN is associated with osteopoikilosis in Buschke-Ollendorf syndrome. Skeletal
      lesions are asymptomatic and are detected by means of iterative X-ray. Their
      management comprises symptomatic care.

PMID- 28760503
TI  - Cryptosporidium and cryptosporidiosis: The Asian perspective.
AB  - This review discusses findings of Cryptosporidium and cryptosporidiosis research
      in Asia and highlights the current situation of Cryptosporidium epidemiology,
      genetic diversity and distribution, and transmission throughout Asia taking into
      account all the available papers published for Cryptosporidium research in Asian
      countries since 2000. This effort will facilitate future research approaches and
      further developments in the understanding of Cryptosporidium epidemiology in
      Asia. The intent is to contribute to improvement in protection measures for
      mitigating the burden associated with this illness in the future.

PMID- 28760504
TI  - Protection against RAGE-mediated neuronal cell death by sRAGE-secreting human
      mesenchymal stem cells in 5xFAD transgenic mouse model.
AB  - Alzheimer's disease (AD), which is the most commonly encountered
      neurodegenerative disease, causes synaptic dysfunction and neuronal loss due to
      various pathological processes that include tau abnormality and amyloid beta
      (Abeta) accumulation. Abeta stimulates the secretion and the synthesis of
      Receptor for Advanced Glycation End products (RAGE) ligand by activating
      microglial cells, and has been reported to cause neuronal cell death in Abeta1-42
      treated rats and in mice with neurotoxin-induced Parkinson's disease. The soluble
      form of RAGE (sRAGE) is known to reduce inflammation, and to decrease microglial
      cell activation and Abeta deposition, and thus, it protects from neuronal cell
      death in AD. However, sRAGE protein has too a short half-life for therapeutic
      purposes. We developed sRAGE-secreting umbilical cord derived mesenchymal stem
      cells (sRAGE-MSCs) to enhance the inhibitory effects of sRAGE on Abeta deposition
      and to reduce the secretion and synthesis of RAGE ligands in 5xFAD mice. In
      addition, these cells improved the viability of injected MSCs, and enhanced the
      protective effects of sRAGE by inhibiting the binding of RAGE and RAGE ligands in
      5xFAD mice. These findings suggest sRAGE protein from sRAGE-MSCs has better
      protection against neuronal cell death than sRAGE protein or single MSC treatment
      by inhibiting the RAGE cell death cascade and RAGE-induce inflammation.

PMID- 28760505
TI  - "Pulmonary embolism diagnostics of pregnant patients: What is the recommended
      clinical pathway considering the clinical value and associated radiation risks of
      available imaging tests?"
AB  - Pulmonary embolism (PE) during pregnancy remains the leading preventable cause of
      maternal morbidity and mortality in the developed countries. Diagnosis of PE in
      pregnant patients is a challenging clinical problem, since pregnancy-related
      physiologic changes can mimic signs and symptoms of PE. Patient mismanagement may
      result into unjustified anticoagulant treatment or unnecessary imaging tests
      involving contrast-related or/and radiation-related risks for both the expectant
      mother and embryo/fetus. On the other hand, missing or delaying diagnosis of PE
      could lead to life-threatening conditions for both the mother and the
      embryo/fetus. Thus, a timely and accurate diagnostic approach is required for the
      optimal management of pregnant patients with suspected PE. Aim of the current
      review is to discuss a pregnancy-specific clinical pathway for the early
      diagnosis of PE with non-ionizing radiation- and ionizing radiation-based imaging
      modalities taking into account previously reported data on diagnostic value of
      available imaging tests, and radiation related concerns.

PMID- 28760506
TI  - A comparison of treatment plan quality between Tri-Co-60 intensity modulated
      radiation therapy and volumetric modulated arc therapy for cervical cancer.
AB  - PURPOSE: To investigate the plan quality of tri-Co-60 intensity-modulated
      radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for cervical
      cancer. METHODS: A total of 20 patients who received postoperative radiotherapy
      for cervical cancer were selected. For each patient, a tri-Co-60 IMRT plan for
      which the target volume was the planning target volume (PTV) generated by adding
      1mm isotropic margins from the clinical target volume (CTV) and a VMAT plan for
      which the target volume was the PTV generated by adding 7mm and 10mm margins from
      the CTV were generated. The tri-Co-60 IMRT plans were generated with the
      ViewRayTM system while the VMAT plans were generated with 15-MV photon beams from
      a linear accelerator (prescription dose=50.4Gy in 28 fractions). RESULTS: The
      average volumes of the PTVs and CTVs were 704.9cc+/-87.8cc and 271.6cc+/-51.6cc,
      respectively. No noticeable differences in the dose-volumetric parameters for the
      target volumes were observed between the tri-Co-60 IMRT and VMAT plans. The
      values of V40Gy for the small bowel and rectal wall, V45Gy of the bladder, and
      V35Gy of the femoral heads for the VMAT plans were 14.6%+/-7.8%, 54.4%+/-4.2%,
      30.0%+/-4.7%, and 8.9%+/-3.3%, respectively. Those of the tri-Co-60 IMRT plans
      were 2.8%+/-2.1%, 23.0%+/-8.9%, 17.1%+/-6.1%, and 0.3%+/-0.4%, respectively.
      CONCLUSIONS: Owing to the target margin reduction capability, the tri-Co-60 IMRT
      plans were more favorable than the VMAT plans for cervical cancer.

PMID- 28760507
TI  - Use of a second-dose calculation algorithm to check dosimetric parameters for the
      dose distribution of a first-dose calculation algorithm for lung SBRT plans.
AB  - PURPOSE: To verify lung stereotactic body radiotherapy (SBRT) plans using a
      secondary treatment planning system (TPS) as an independent method of
      verification and to define tolerance levels (TLs) in lung SBRT between the
      primary and secondary TPSs. METHODS: A total of 147 lung SBRT plans calculated
      using X-ray voxel Monte Carlo (XVMC) were exported from iPlan to Eclipse in DICOM
      format. Dose distributions were recalculated using the Acuros XB (AXB) and the
      anisotropic analytical algorithm (AAA), while maintaining monitor units (MUs) and
      the beam arrangement. Dose to isocenter and dose-volumetric parameters, such as
      D2, D50, D95 and D98, were evaluated for each patient. The TLs of all parameters
      between XVMC and AXB (TLAXB) and between XVMC and AAA (TLAAA) were calculated as
      the mean+/-1.96 standard deviations. RESULTS: AXB values agreed with XVMC values
      within 3.5% for all dosimetric parameters in all patients. By contrast, AAA
      sometimes calculated a 10% higher dose in PTV D95 and D98 than XVMC. The TLAXB
      and TLAAA of the dose to isocenter were -0.3+/-1.4% and 0.6+/-2.9%, respectively.
      Those of D95 were 1.3+/-1.8% and 1.7+/-3.6%, respectively. CONCLUSIONS: This
      study quantitatively demonstrated that the dosimetric performance of AXB is
      almost equal to that of XVMC, compared with that of AAA. Therefore, AXB is a more
      appropriate algorithm for an independent verification method for XVMC.

PMID- 28760508
TI  - Effects of gamma-low dose irradiation on skin flap survival in rats.
AB  - PURPOSE: Skin flap necrosis due to inadequate blood supply has remained a common
      postoperative problem in constructive surgery. As low-dose irradiation (LDI) has
      been shown to promote the wound-healing process, this study aims to investigate
      whether LDI could increase neovascularization and skin flap survival in rats.
      METHODS: McFarlane flaps were created in 21 male rats, which were divided into
      one control and two treatment groups (Ta and Tb). The treatment groups received a
      whole body single dose of 100cGy gamma ray irradiation before (Tb) and after (Ta)
      flap surgery. The flap survival area was evaluated after seven days. The skin
      samples were collected for histological analysis and determining the vascular
      endothelial growth factor (VEGF) using the immunohistochemical method. Serum
      malondialdehyde (MDA) was examined with the kit. RESULTS: The mean areas of flap
      survival were 56.7+/-3.24, 61.7+/-2.6, and 66.5+/-3.82 in the control, Tb, and Ta
      groups, respectively. There were significant differences between the Tb and Ta
      groups in comparison with the control group (P<0.05 and P<0.01, respectively).
      Compared with the control group (8.0+/-0.73), the mean numbers of the blood
      vessels in the Ta group (22+/-1.24) and the Tb group (14+/-1.29) were
      significantly higher (P<0.001 and P<0.01). Moreover, the mean numbers of the VEGF
      positive cells in the Ta group (4.5+/-1.04) were significantly higher (P<0.05)
      than the control group (2.5+/-0.83). However, no significant differences in the
      MDA levels were observed among the groups. CONCLUSION: The findings of this study
      suggest that LDI has the potential to promote neovascularization to improve flap
      survival.

PMID- 28760509
TI  - Pulmonary mechanic and lung histology induced by Crotalus durissus cascavella
      snake venom.
AB  - This study have analyzed the pulmonary function in an experimental model of acute
      lung injury, induced by the Crotalus durissus cascavella venom (C. d. cascavella)
      (3.0 MUg/kg - i.p), in pulmonary mechanic and histology at 1 h, 3 h, 6 h, 12 h
      and 24 h after inoculation. The C. d. cascavella venom led to an increase in
      Newtonian Resistance (RN), Tissue Resistance (G) and Tissue Elastance (H) in all
      groups when compared to the control, particularly at 12 h and 24 h. The
      Histeresivity (eta) increased 6 h, 12 h and 24 h after inoculation. There was a
      decrease in Static Compliance (CST) at 6 h, 12 h and 24 h and inspiratory
      capacity (IC) at 3 h, 6 h, 12 h and 24 h. C. d. cascavella venom showed
      significant morphological changes such as atelectasis, emphysema, hemorrhage,
      polymorphonuclear inflammatory infiltrate, edema and congestion. After a
      challenge with methacholine (MCh), RN demonstrated significant changes at 6, 12
      and 24 h. This venom caused mechanical and histopathological changes in the lung
      tissue; however, its mechanisms of action need further studies in order to better
      elucidate the morphofunctional lesions.

PMID- 28760510
TI  - Structural cutaneous adaptations for defense in toad (Rhinella icterica) parotoid
      macroglands.
AB  - Toads have a pair of glandular accumulations on each side of the dorsal region of
      the head known as parotoid macroglands. These macroglands consist of secretory
      units (granular glands), each one capped with an epithelial plug. When
      threatened, toads point one of the parotoids toward the aggressor, and if the
      aggressor squeezes the parotoid with its teeth, jets of poison will come out of
      the secretory units and hit the predator's oral mucosa, thereby causing
      poisoning. Our study focused on the mechanism of parotoid function by comparing
      parotoids from toads naturally attacked by dogs with those manually compressed.
      We verified that the process of glandular emptying in response to dog bites is
      very similar to that following manual compression. We observed that the structure
      of the plug plays an essential role in the release of the poison jets. Our
      results suggest that the parotoids may act as "bulletproof vests," reducing the
      impact of the force exerted by predator attacks, and thus may function as a
      passive antipredator mechanism.

PMID- 28760511
TI  - Interarm blood pressure difference in a post-stroke population.
AB  - An increased interarm systolic blood pressure (SBP) difference of >=10 mm Hg is
      associated with increased cardiovascular risk and a difference of >=15 mm Hg with
      increased cerebrovascular risk. The stroke population presents a high-risk group
      for future cardiovascular and cerebrovascular events and therefore estimation of
      interarm SBP difference as a predictive tool may assist with further secondary
      stroke prevention. The aim of the study was to determine the prevalence of
      interarm SBP and diastolic blood pressure difference in a post-stroke population.
      A comprehensive assessment of secondary risk factors along with blood pressure
      measurements were taken 6-months' post-ischemic stroke from the Action on
      Secondary Prevention Interventions and Rehabilitation in Stroke cohort.
      Descriptive and logistic regression analyses were performed. Odds ratios and 95%
      confidence intervals are presented. Two hundred thirty-eight (M: F,139:99; mean
      age, 68.4 years) of 256 patients followed up at 6 months post-stroke had suitable
      blood pressure readings from both arms. Ninety-six patients (40.3%) had an
      interarm SBP difference of >=10 mm Hg and 49 (20.6%) had a difference of >=15 mm
      Hg. A history of hypertension, diabetes, smoking, and obesity was not
      significantly associated with an increased risk of interarm SBP difference. After
      multivariate logistic analysis, a history of alcohol excess was associated with
      an increased IASBP >=15 mm Hg (odds ratio 2.32, 95% confidence interval 1.03
      5.22). We have demonstrated that interarm SBP difference is commonly seen in a
      post stroke population.

PMID- 28760512
TI  - Self-rated versus Caregiver-rated Health for Patients with Mild Dementia as
      Predictors of Patient Mortality.
AB  - OBJECTIVE: Self-assessment of health is a strong and independent predictor of
      mortality for cognitively intact people. Because the ability of patients with
      dementia to rate their own health is questionable, caregiver-rated health for
      patients may serve as a proxy. The authors aimed to validate and compare self-
      and caregiver-rated health for patients with dementia as independent predictors
      of patient mortality. METHODS: This was a post-hoc analysis of data from The
      Danish Alzheimer's Disease Intervention Study, a randomized controlled trial of
      psychosocial intervention for 330 patients with mild dementia and their
      caregivers with a 36-month follow-up. Patients and caregivers rated patients'
      health on the Euro Quality of Life Visual Analog Scale (EQ-VAS) from 0 (worst) to
      100 (best). The ability of self- and caregiver-rated health for the patient to
      predict patient mortality was analyzed as hazard ratios (HRs) from Cox
      proportional hazard regression models, controlling for age, depression,
      comorbidities, functional level, quality of life, and randomization group.
      RESULTS: Compared with the highest scores of 80-100, caregiver-rated EQ-VAS
      scores < 50 had an HR of 9.8 (95% CI: 2.9-33.1), scores between 50 and 64 had an
      HR of 3.8 (95% CI: 1.2-12.3), and scores between 65 and 79 had an HR of 4.6 (95%
      CI: 1.4-14.7). Self-rated EQ-VAS did not statistically significantly predict
      mortality. CONCLUSION: Caregiver-rated health for patients with mild dementia
      using the EQ-VAS was shown to be an independent predictor of patient mortality
      with a dose-response pattern but patient-rated EQ-VAS was not.

PMID- 28760513
TI  - Depressive Symptoms in Recipients of Home- and Community-Based Services in the
      United States: Are Older Adults Receiving the Care They Need?
AB  - OBJECTIVE: To understand unmet depression needs of older adults, the current
      study investigates depressive symptoms, psychiatric treatment, and home- and
      community-based service (HCBS) use in a nationally representative sample of older
      adults in the United States. METHODS: Participants included 5,582 adults aged 60
      and over from the 2010-2012 waves of the nationally representative Health and
      Retirement Study. Weighted bivariate analyses were used to examine the frequency
      of depressive symptoms (Center for Epidemiologic Studies Depression Scale) and
      psychiatric treatment among HCBS recipients compared with non-HCBS recipients.
      Weighted logistic regression models were used to evaluate the effect of
      depressive symptoms on HCBS use. RESULTS: HCBS recipients had a higher frequency
      of depressive symptoms compared with nonrecipients (27.5% versus 10.4%,
      respectively). In particular, transportation service recipients had the highest
      frequency of depressive symptoms (37.5%). HCBS recipients with depressive
      symptoms were no more likely than nonrecipients to receive psychiatric services.
      Depressive symptoms were associated with HCBS use, above and beyond
      sociodemographic and health risk factors. CONCLUSION: Depressive symptoms are
      more frequent among HCBS recipients compared with nonrecipients; however,
      depressed HCBS recipients are no more likely to receive psychiatric services,
      suggesting unmet depression needs. HCBS may be a key setting for depression
      detection and delivery of mental health interventions.

PMID- 28760514
TI  - !HOLA, Amigos! Toward Preventing Anxiety and Depression in Older Latinos.
AB  - Given the prevalence and morbidity of depression and anxiety in later life, the
      inadequacies of current treatment approaches for averting years living with
      disability, the disparities in access to the mental healthcare delivery system,
      and the workforce shortages to meet the mental health needs of older Latinos,
      development and testing of innovative strategies to prevent depression and
      anxiety are of great public health significance and have the potential to change
      practice. Although impediments to good depression and anxiety outcomes exist for
      all older adults, they are even more pronounced for older Latinos, who tend to
      have fewer socioeconomic resources. These factors underscore the need for
      prevention-based interventions that are effective, scalable, relevant,
      respectful, and specific to this population. The Happy Older Latinos are Active
      (HOLA) program is a community health worker-led, multicomponent, health promotion
      intervention. The diverse needs and circumstances of older Latinos (highly
      sedentary, culture-specific health beliefs, service disparities) were
      incorporated into the design of HOLA to reduce risk factors and improve health
      related outcomes associated with common mental disorders in this group. The
      authors describe HOLA (highlighted in this case example) and why health promotion
      interventions like HOLA may hold promise as effective, practical, and
      nonstigmatizing interventions for preventing common mental disorders in older
      Latinos who are at risk for developing these disorders.

PMID- 28760515
TI  - MRI Markers of Neurodegenerative and Neurovascular Changes in Relation to
      Postoperative Delirium and Postoperative Cognitive Decline.
AB  - Postoperative delirium (POD) and postoperative cognitive decline (POCD) are
      common in elderly patients. The aim of the present review was to explore the
      association of neurodegenerative and neurovascular changes with the occurrence of
      POD and POCD. Fifteen MRI studies were identified by combining multiple search
      terms for POD, POCD, and brain imaging. These studies described a total of 1,422
      patients and were all observational in design. Neurodegenerative changes (global
      and regional brain volumes) did not show a consistent association with the
      occurrence of POD (four studies) or POCD (two studies). In contrast,
      neurovascular changes (white matter hyperintensities and cerebral infarcts) were
      more consistently associated with the occurrence of POD (seven studies) and POCD
      (five studies). In conclusion, neurovascular changes appear to be consistently
      associated with the occurrence of POD and POCD, and may identify patients at
      increased risk of these conditions. Larger prospective studies are needed to
      study the consistency of these findings and to unravel the underlying
      pathophysiological mechanisms.

PMID- 28760516
TI  - [Rare complication of renal transplantation: Emphysematous pyelonephritis].
AB  - Emphysematous pyelonephritis is a necrotizing infection of the renal parenchyma
      and peri-renal tissues, characterized by the presence of air within the
      parenchyma of the urinary tract and peri-renal space. This is a severe
      complication, which involves the functional prognosis of the kidney and the
      patient's prognosis. The emphysematous pyelonephritis is a rare complication of
      renal transplantation. Its gravity is linked particularly to the fragility of
      immunosuppressed patients. The authors report the case of an emphysematous
      pyelonephritis having occurred 9 months after transplantation in a patient 58
      years. The evolving risks and therapeutic modalities will be outlined and
      discussed.

PMID- 28760517
TI  - The International Glossary on Infertility and Fertility Care, 2017.
AB  - STUDY QUESTION: Can a consensus and evidence-driven set of terms and definitions
      be generated to be used globally in order to ensure consistency when reporting on
      infertility issues and fertility care interventions, as well as to harmonize
      communication among the medical and scientific communities, policy-makers, and
      lay public including individuals and couples experiencing fertility problems?
      SUMMARY ANSWER: A set of 283 consensus-based and evidence-driven terminologies
      used in infertility and fertility care has been generated through an inclusive
      consensus-based process with multiple stakeholders. WHAT IS KNOWN ALREADY: In
      2006 the International Committee for Monitoring Assisted Reproductive
      Technologies (ICMART) published a first glossary of 53 terms and definitions. In
      2009 ICMART together with WHO published a revised version expanded to 87 terms,
      which defined infertility as a disease of the reproductive system, and increased
      standardization of fertility treatment terminology. Since 2009, limitations were
      identified in several areas and enhancements were suggested for the glossary,
      especially concerning male factor, demography, epidemiology and public health
      issues. STUDY DESIGN, SIZE, DURATION: Twenty-five professionals, from all parts
      of the world and representing their expertise in a variety of sub-specialties,
      were organized into five working groups: clinical definitions; outcome
      measurements; embryology laboratory; clinical and laboratory andrology; and
      epidemiology and public health. Assessment for revisions, as well as expansion on
      topics not covered by the previous glossary, were undertaken. A larger group of
      independent experts and representatives from collaborating organizations further
      discussed and assisted in refining all terms and definitions.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Members of the working groups and
      glossary co-ordinators interacted through electronic mail and face-to-face in
      international/regional conferences. Two formal meetings were held in Geneva,
      Switzerland, with a final consensus meeting including independent experts as well
      as observers and representatives of international/regional scientific and patient
      organizations. MAIN RESULTS AND THE ROLE OF CHANCE: A consensus-based and
      evidence-driven set of 283 terminologies used in infertility and fertility care
      was generated to harmonize communication among health professionals and
      scientists as well as the lay public, patients and policy makers. Definitions
      such as 'fertility care' and 'fertility awareness' together with terminologies
      used in embryology and andrology have been introduced in the glossary for the
      first time. Furthermore, the definition of 'infertility' has been expanded in
      order to cover a wider spectrum of conditions affecting the capacity of
      individuals and couples to reproduce. The definition of infertility remains as a
      disease characterized by the failure to establish a clinical pregnancy; however,
      it also acknowledges that the failure to become pregnant does not always result
      from a disease, and therefore introduces the concept of an impairment of function
      which can lead to a disability. Additionally, subfertility is now redundant,
      being replaced by the term infertility so as to standardize the definition and
      avoid confusion. LIMITATIONS, REASONS FOR CAUTION: All stakeholders agreed to the
      vast majority of terminologies included in this glossary. In cases where
      disagreements were not resolved, the final decision was reached after a vote,
      defined before the meeting as consensus if passed with 75%. Over the following
      months, an external expert group, which included representatives from non
      governmental organizations, reviewed and provided final feedback on the glossary.
      WIDER IMPLICATIONS OF THE FINDINGS: Some terminologies have different
      definitions, depending on the area of medicine, for example demographic or
      clinical as well as geographic differences. These differences were taken into
      account and this glossary represents a multinational effort to harmonize
      terminologies that should be used worldwide. STUDY FUNDING/COMPETING INTERESTS:
      None. TRIAL REGISTRATION NUMBER: N/A.

PMID- 28760518
TI  - Reliability of smartphone-based teleradiology for evaluating thoracolumbar spine
      fractures: statistical issue to avoid misinterpretation.

PMID- 28760519
TI  - Reply to letter to the editor titled "Reliability of smartphone-based
      teleradiology for evaluating thoracolumbar spine fractures: statistical issue to
      avoid misinterpretation".

PMID- 28760520
TI  - Counterpoint: Not Everything Significant Is Significant.

PMID- 28760521
TI  - Time Is Not on Our Side: How Radiology Practices Should Manage Customer Queues.
AB  - As health care shifts toward patient-centered care, wait times have received
      increasing scrutiny as an important metric for patient satisfaction. Long queues
      form when radiology practices inefficiently service their customers, leading to
      customer dissatisfaction and a lower perception of value. This article describes
      a four-step framework for radiology practices to resolve problematic queues: (1)
      analyze factors contributing to queue formation; (2) improve processes to reduce
      service times; (3) reduce variability; (4) address the psychology of queues.

PMID- 28760522
TI  - Factors Associated With Pain Frequency Among Adults With Chronic Conditions.
AB  - CONTEXT: Chronic pain affects approximately 100 million Americans, but little is
      known about the factors associated with pain frequency. OBJECTIVES: This article
      examines participants' sociodemographics, medical history, health care access and
      utilization, self-management barriers, and social support associated with pain
      frequency among a sample of middle-aged and older adults with one or more chronic
      condition. METHODS: Data were from the National Council on Aging Chronic Care
      Survey. An ordinal regression model was fitted to examine factors associated with
      self-reported pain frequency. RESULTS: Having more chronic conditions (P <
      0.001), taking more medication daily (P < 0.001), and visiting the physician five
      or more times a year (P = 0.011) were associated with more frequent pain. Always
      getting the help and support needed to manage their health problems was
      associated with less frequent pain (P < 0.001). CONCLUSION: More attention should
      be given to pain management during interactions with health care providers.
      Providing resources and support for disease self-management may help reduce pain
      frequency and self-management in middle-aged and older adults with chronic
      conditions.

PMID- 28760523
TI  - Brief Training on Patient Anger Increases Oncology Providers' Self-Efficacy in
      Communicating With Angry Patients.
AB  - CONTEXT: Anger is a common reaction to pain and life-limiting and life
      threatening illness, is linked to higher levels of pain, and may disrupt
      communication with medical providers. Anger is understudied compared with other
      emotions in mental health and health care contexts, and many providers have
      limited formal training in addressing anger. OBJECTIVES: The objective of this
      study was to assess if a brief provider training program is a feasible method for
      increasing providers' self-efficacy in responding to patient anger. METHODS:
      Providers working in stem cell transplant and oncology units attending a brief
      training session on responding to patient anger. The program was informed by
      cognitive behavioral models of anger and included didactics, discussion, and
      experiential training on communication and stress management. RESULTS: Provider
      rated self-efficacy was significantly higher for nine of 10 skill outcomes (P <
      .005) including acknowledging patient anger, discussing anger, considering
      solutions, and using relaxation to manage their own distress. All skill increases
      were large in magnitude (Cohen's d = 1.18-2.22). CONCLUSION: Providers found the
      program to be useful for increasing their confidence in addressing patient anger.
      Discussion, didactics, and experiential exercises can support provider awareness
      of anger, shape adaptive communication, and foster stress management skills.

PMID- 28760524
TI  - Gaps in Provision of Primary and Specialty Palliative Care in the Acute Care
      Setting by Race and Ethnicity.
AB  - CONTEXT: Previous research has identified a large unmet need in provision of
      specialist-level palliative care services in the hospital. How much of this gap
      is filled by primary palliative care provided by generalists or nonpalliative
      specialists has not been quantified. Estimates of racial and ethnic disparities
      have been inconsistent. OBJECTIVES: The objective of this study was to 1)
      estimate primary and specialty palliative care delivery and to measure unmet
      needs in the inpatient setting and 2) explore racial and ethnic disparities in
      palliative care delivery. METHODS: This was a cross-sectional, retrospective
      study of 55,658 adult admissions to two acute care hospitals in the Bronx in
      2013. Patients with palliative care needs were identified by criteria adapted
      from the literature. The primary outcomes were delivery of primary and specialist
      level palliative care. RESULTS: In all, 18.5% of admissions met criteria for
      needing palliative care. Of those, 18% received specialist-level palliative care,
      an estimated 30% received primary palliative care, and 37% had no evidence of
      palliative care or advance care planning. Black and Hispanic patients were not
      less likely to receive specialist-level palliative care (adjusted odds ratio [OR]
      black patients = 1.18, 95% CI 0.98, 1.42; adjusted OR Hispanic patients = 1.24,
      95% CI 1.04, 1.48), but they were less likely to receive primary palliative care
      (adjusted OR black patients = 0.41, 95% CI 0.20, 0.84; adjusted OR Hispanic
      patients = 0.48, 95% CI 0.25, 0.94). CONCLUSION: Even when considering primary
      and specialty palliative care, hospitalized patients have a high prevalence of
      unmet palliative care need. Further research is needed understand racial and
      ethnic disparities in palliative care delivery.

PMID- 28760525
TI  - Using daily excessive concentration hours to explore the short-term mortality
      effects of ambient PM2.5 in Hong Kong.
AB  - We developed a novel indicator, daily excessive concentration hours (DECH), to
      explore the acute mortality impacts of ambient fine particulate matter pollution
      (PM2.5) in Hong Kong. The DECH of PM2.5 was calculated as daily concentration
      hours >25 MUg/m3. We applied a generalized additive models to quantify the
      association between DECH and mortality with adjustment for potential confounders.
      The results showed that the DECH was significantly associated with mortality. The
      excess mortality risk for an interquartile range (565 MUg/m3*hours) increase in
      DECH of PM2.5 was 1.65% (95% CI: 1.05%, 2.26%) for all natural mortality at lag
      02 day, 2.01% (95% CI: 0.82%, 3.21%) for cardiovascular mortality at lag 03 days,
      and 1.41% (95% CI: 0.34%, 2.49%) for respiratory mortality at lag 2 day. The
      associations remained consistent after adjustment for gaseous air pollutants
      (daily mean concentration of SO2, NO2 and O3) and in alternative model
      specifications. When compared to the mortality burden of daily mean PM2.5, DECH
      was found to be a relatively conservative indicator. This study adds to the
      evidence by showing that daily excessive concentration hours of PM2.5 might be a
      new predictor of mortality in Hong Kong.

PMID- 28760526
TI  - Synergistic coagulation of GO and secondary adsorption of heavy metal ions on
      Ca/Al layered double hydroxides.
AB  - With the extensive application of graphene oxide (GO), it is noticeable that part
      of GO is directly/indirectly released into the environment and widespread
      research indicated that it had adverse influences on human health and ecological
      balance. In this work, a novel nanobelt-like Ca/Al layered double hydroxides (CA
      LDH) was synthesized and applied as efficient coagulant for the removal of GO
      from aqueous solutions. The results indicated that neutral pH, co-existing
      cations and higher temperature were beneficial to the coagulation of GO. The
      sequence of cation effect for promoting of GO coagulation was Ca2+ > Mg2+ > K+ >
      Na+, whereas the effect of anions on GO coagulation was PO43- > CO32- > SO42- >
      Cl-. Comparing with anions, the cations showed more dominate effect for GO
      coagulation than anions. Hydrogen bonds and electrostatic interaction were the
      main coagulation mechanisms for GO coagulation, which were evidenced by FT-IR and
      XPS analysis. Specifically, for the first time, the reclaimed product of CA-LDH
      after GO coagulation (CA-LDH + GO) was applied as adsorbents for the secondary
      application in the removal of heavy metal ions from aqueous solutions.
      Interestingly, the CA-LDH + GO still had high adsorption capacities, i.e., the
      maximum adsorption capacities (qmax) for Cu(II), Pb(II), and Cr(VI) were 122.7
      mg/g, 221.2 mg/g and 64.4 mg/g, respectively, higher than other similar
      materials. This paper highlighted the LDH-based nanomaterials are promising
      materials for the elimination of environmental pollutants and the migration and
      transformation of carbon nanomaterials in the natural environment.

PMID- 28760527
TI  - Using normal ranges for interpreting results of monitoring and tiering to guide
      future work: A case study of increasing polycyclic aromatic compounds in lake
      sediments from the Cold Lake oil sands (Alberta, Canada) described in Korosi et
      al. (2016).
AB  - Since the publishing of the Kelly et al. papers (2009, 2010) describing elevated
      contaminants in snow near the Alberta oil sands, there has been a significant
      expansion of monitoring efforts, enhanced by $50M a year contributed by industry
      to a regional Joint Oil Sands Monitoring (JOSM) program. In parallel to the
      intensification of research and monitoring efforts, including expansion of
      measured indicators, techniques for chemical analysis have also become more
      sensitive. Both factors contribute to the increased sensitivity and power, and
      improve our capacity to detect any change. The increase in capability requires a
      counterbalance to account for trivial change. This can be done using an
      interpretative approach that requires contextualization of differences to
      meaningfully inform environmental monitoring programs and provide focus for
      action. Experience obtained through 25 years of involvement with Canada's
      Environmental Effects Monitoring (EEM) program has shown that a tiered program
      informed by triggers can provide the context to make decisions about monitoring
      priorities. Here we provide a potential interpretation framework using a case
      study around the Korosi et al. (2016) study which found recent increases in
      alkylated polycyclic aromatic compounds (aPACs) in the Cold Lake in situ oil
      sands area. Public contaminant profiles from the JOSM studies in the oil sands
      region are used to evaluate the changes using an interpretation framework based
      on estimated normal ranges using existing data for site-specific, local and
      regional (distant) levels that was modelled after the tiered Canadian EEM design.

PMID- 28760528
TI  - 3-O-Substituted-3',4',5'-trimethoxyflavonols: Synthesis and cell-based evaluation
      as anti-prostate cancer agents.
AB  - Twenty-two 3-O-substituted-3',4',5'-trimethoxyflavonols have been designed and
      synthesized for their anti-proliferative activity towards three human prostate
      cancer cell lines. Our results indicate that most of them are significantly more
      potent than the parent 3',4',5'-trimethoxyflavonol in inhibiting the cell
      proliferation in PC-3 and LNCaP prostate cancer cell models. 3-O-Substituted
      3',4',5'-trimethoxyflavonols have generally higher potency towards PC-3 and LNCaP
      cell lines than the DU145 cell line. Incorporation of an ethyl group to 3-OH of
      3',4',5'-trimethoxyflavonol leads to 3-O-ethyl-3',4',5'-trimethoxyflavonol as the
      optimal derivative with up to 36-fold enhanced potency as compared with the
      corresponding lead compound 3',4',5'-trimethoxyflavonol, but with reversed PC-3
      cell apoptotic response. Introduction of a dipentylaminopropyl group to 3-OH
      increases not only the antiproliferative potency but also the ability in
      activating PC-3 cell apoptosis. Our findings imply that modification on 3-OH of
      trimethoxyflavonol can further enhance its in vitro anti-proliferative potency
      and PC-3 cell apoptosis induction.

PMID- 28760530
TI  - Isolation and lipolytic activity of eurycomanone and its epoxy derivative from
      Eurycoma longifolia.
AB  - Eurycomanone (1) and 13beta,21-epoxyeurycomanone (2) were isolated from Eurycoma
      longifolia for studies of lipolytic activity. Compound 1 enhanced lipolysis in
      adipocytes with an EC50 of 14.6MUM, while its epoxy derivate, compound 2, had a
      stronger activity with an EC50 of 8.6MUM. Based on molecular mechanistic study
      using several specific inhibitors to lipolytic signaling pathways, it was found
      that PKA inhibitor totally diminished the lipolytic activity of 1 and 2. Further
      immunoblotting analysis confirmed the activation of phosphorylated PKA by both 1
      and 2. With the growing need to develop new anti-obesity agents, eurycomanone and
      its epoxy derivate can be used as promising lead compounds to target lipid
      catabolism.

PMID- 28760532
TI  - Corrigendum to 'Meta-analysis of data from animal studies: A practical guide':
      [Journal of Neuroscience Methods 221 (2014) 92-102].

PMID- 28760529
TI  - Discovery of a novel B-cell lymphoma 6 (BCL6)-corepressor interaction inhibitor
      by utilizing structure-based drug design.
AB  - B-cell lymphoma 6 (BCL6) is a transcriptional repressor that can form complexes
      with corepressors via protein-protein interactions (PPIs). The complexes of BCL6
      and corepressors play an important role in the formation of germinal centers
      (GCs), and differentiation and proliferation of lymphocytes. Therefore, BCL6
      corepressor interaction inhibitors would be drug candidates for managing
      autoimmune diseases and cancer. Starting from high-throughput screening hits 1a
      and 2a, we identified a novel BCL6-corepressor interaction inhibitor 8c (cell
      free enzyme-linked immunosorbent assay [ELISA] IC50=0.10uM, cell-based mammalian
      two-hybrid [M2H] assay IC50=0.72uM) by utilizing structure-based drug design
      (SBDD) based on an X-ray crystal structure of 1a bound to BCL6. Compound 8c also
      showed a good pharmacokinetic profile, which was acceptable for both in vitro and
      in vivo studies.

PMID- 28760531
TI  - Structure based drug design of Pim-1 kinase followed by pharmacophore guided
      synthesis of quinolone-based inhibitors.
AB  - Over expression of Human phosphatidyl inositol mannoside kinases isoform 1 (Pim-1
      kinase) has been reported in several leukemia and solid tumors. Our continuous
      interest to reveal the secrecies of the mysterious Pim-1 kinase binding pocket
      has led us to employ a structure based drug design procedure based on receptor
      ligand pharmacophore generation protocol implemented in Discovery Studio 4.5 (DS
      4.5). Subsequently, we collected 104 crystal structures of Pim-1 kinase from the
      Protein Data Bank (PDB) and used them to generate pharmacophores based on the
      anticipated co-crystallized ligand-Pim 1 kinase receptor interactions. All
      selected pharmacophoric features were enumerated and only those that had
      corresponding valuable receptor-ligand interactions were retained. This was
      followed by modeling all pharmacophore combinations and scoring them according to
      their Receiver Operating Characteristic (ROC) curve analysis parameters as well
      as a DS.4.5 built-in Genetic Function Algorithm (GFA) validating model.
      Accordingly, 111 pharmacophores resulted with acceptable ROC performances;
      1XWS_2_04, 2BIK_2_06, and 1XWS_2_06 (ROC AUC value of: 0.770, 0.743 and 0.741
      respectively) were the best pharmacophores. These pharmacophores were employed to
      guide the synthesis of new series of 7-[(2-Carboxyethyl)amino]-1-substituted-6
      fluoro-8-nitro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid and their reduced 8
      amino derivatives. The synthesized compounds were later evaluated for their Pim-1
      kinase inhibitory potencies. Of which the most potent illustrated an IC50 value
      of 0.29uM against Pim-1 kinase.

PMID- 28760533
TI  - Reliability of EUS indices to detect inflammation in ulcerative colitis.
AB  - BACKGROUND AND AIMS: EUS is a potentially useful modality to assess severity of
      inflammation in ulcerative colitis (UC). We assessed the reliability of existing
      EUS indices and correlated them with endoscopic and histologic scores. METHODS:
      Four blinded endosonographers assessed 58 endoscopic and EUS videos in
      triplicate, from patients with UC. Intrarater and interrater reliability of the
      hyperemia and Tsuga scores were estimated by using intra-class correlation
      coefficients (ICCs). Correlation with the Mayo endoscopy score, modified Baron
      score (MBS), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Geboes
      histopathology score (GHS) were calculated by using bootstrapping methods. A RAND
      consensus process led to development of standardized definitions and a revised
      EUS-UC score. RESULTS: ICCs for intrarater reliability were 0.76 (95% confidence
      interval [CI], 0.71-0.80) for the hyperemia score and 0.85 (95% CI, 0.79-0.89)
      for the Tsuga score. Corresponding values for interrater reliability were 0.34
      (95% CI, 0.25-0.42) and 0.36 (95% CI, 0.24-0.46). Correlation between hyperemia
      and Tsuga scores to Mayo scoring system, MBS, UCEIS, and the GHS were 0.39 (95%
      CI, 0.15-0.61) and 0.28 (95% CI, 0.04-0.51), 0.38 (95% CI, 0.16-0.57) and 0.25
      (95% CI, -0.01-0.48), 0.41 (95% CI, 0.16-0.62) and 0.27 (95% CI, 0.01-0.50), 0.37
      (95% CI, -0.01-0.48) and 0.24 (95% CI, 0.13-0.57), respectively. The revised EUS
      UC score included bowel wall thickening, depth of inflammation, and hyperemia.
      CONCLUSIONS: Although substantial to almost perfect intrarater agreement existed
      for EUS indices in UC, interrater agreement was fair. Standardization of item
      definitions with development of a revised evaluative instrument has potential
      application as an evaluative and prognostic tool for UC. (Clinical trial
      registration number: NCT01852760.).

PMID- 28760534
TI  - An analysis of factors related to the effect of sublingual immunotherapy on
      Japanese cedar pollen induced allergic rhinitis.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) can improve the symptoms of allergic
      rhinitis and modify its natural history; however, its efficacy varies among
      patients. This study aimed to determine which factors modify the effect of SLIT
      through post hoc analysis of a previous phase 3 trial of standardized Japanese
      cedar (JC) pollen extract (CEDARTOLEN(r)). METHODS: The study included 482
      patients who had previously completed a phase 3 trial during two seasons. The
      SLIT and placebo groups each contained 241 subjects. Because pollen dispersal
      differed in the two seasons, we identified good and poor responders from the SLIT
      group in the 2nd season. We compared patient baseline characteristics, changes in
      serum immunoglobulin, and severity of symptoms in the 1st season between good and
      poor responders, as well as between SLIT and placebo groups. RESULTS: When we
      compared the baseline characteristics of good and poor responders, a significant
      difference was observed in body mass index (BMI) such that the patients with BMI
      >=25 presented with lower treatment efficacy. No significant difference was
      observed in correlation with any other factors or treatment-induced alterations
      of serum immunoglobulin levels. We found that 75.3% of the patients with moderate
      symptoms and 50.9% of the patients with severe or very severe symptoms in the 1st
      season met our criteria for good responders in the 2nd season. CONCLUSIONS: BMI
      might modify the effect of SLIT; however, other factors were not related clearly.
      The severity of symptoms in the 1st season of treatment does not predict that in
      the 2nd season.

PMID- 28760535
TI  - A Randomized Phase I Study to Assess the Effect of Alcohol on the
      Pharmacokinetics of an Extended-release Orally Disintegrating Tablet Formulation
      of Amphetamine in Healthy Adults.
AB  - PURPOSE: There is a strong association between attention-deficit/hyperactivity
      disorder (ADHD) and alcohol abuse, yet no studies have systematically assessed
      the effect of alcohol on the pharmacokinetics of psychostimulants such as
      amphetamine (AMP) in vivo. This study evaluated the effects of alcohol on the
      rate and extent of absorption of AdzenysTM XR-ODT*, a new extended-release orally
      disintegrating AMP tablet (AMP XR-ODT) for ADHD. METHODS: A Phase I single-dose,
      open-label study was conducted in 32 healthy adults. Participants were split into
      2 cohorts, allowing for close monitoring of safety profile and tolerability, and
      were randomized 1:1:1:1 to receive treatment in 1 of 4 sequences. Each treatment
      included the administration of a single 18.8-mg dose of AMP XR-ODT, followed by
      240 mL of deionized water or 4%, 20%, or 40% ethanol. Blood samples were
      collected at prespecified time points. The pharmacokinetic profiles of d- and l
      AMP were comparable across treatment groups. FINDINGS: There was no change in the
      extent of absorption for d- or l-AMP with alcohol coingestion and no dose dumping
      of the extended-release portion of the formulation. The 90% CIs for the geometric
      mean ratios (4%, 20%, and 40% ethanol versus water) for Cmax and systemic
      exposure (AUC0-5, AUClast, and AUC0-infinity) were within 80% to 125%. Adverse
      events were mild to moderate and were consistent with the known adverse event
      profile for AMP XR-ODT or alcohol. IMPLICATIONS: Varying concentrations of
      alcohol (4%-40%) did not significantly alter the pharmacokinetic profile of AMP
      XR-ODT. These findings are relevant to clinicians who have concerns about alcohol
      use and/or abuse when treating ADHD.

PMID- 28760536
TI  - Validation of the Fautrel classification criteria for adult-onset Still's
      disease.
AB  - OBJECTIVES: To validate the Fautrel classification criteria for adult-onset
      Still's disease (AOSD) and to compare the discriminative performance to that of
      the Yamaguchi criteria. METHODS: We retrospectively reviewed the medical charts
      of 426 patients who had serum ferritin level and percentage glycosylated ferritin
      assayed at the biochemistry laboratory of Bichat Hospital. Medical data were
      extracted by use of a standardized form. All clinical, biological, and imaging
      features were collected, as well, evidence favoring an alternative diagnosis,
      specifically symptoms suggestive of other immune-mediated inflammatory diseases
      (IMID) or active infections. Patients were classified as AOSD patients or
      controls according to a predefined procedure, including consultation with a
      multidisciplinary expert group. Algorithms corresponding to the Fautrel and
      Yamaguchi classification criteria were applied for each patient. RESULTS: In all,
      54 AOSD and 278 control patients were included. For the Fautrel criteria, the
      sensitivity was 87.0%, specificity 97.8%, and positive and negative predictive
      values 88.7% and 97.5%, respectively. For the standard Yamaguchi set-without
      strict application of exclusion criteria-the sensitivity was 96.3%, specificity
      98.9%, and positive and negative predictive values 94.5% and 99.3%, respectively.
      If we applied a stricter definition of exclusion criteria, the sensitivity of the
      Yamaguchi set decreased to 31.5%. As wall, 37 AOSD diagnoses were missed.
      CONCLUSION: This study validates the Fautrel classification criteria with a
      cohort independent of that used for the original publication. This criteria set
      demonstrates good sensitivity and specificity, overcomes exclusion criteria, and
      includes glycosylated ferritin level. It also confirms the high discriminative
      power of the Yamaguchi criteria, albeit substantially affected by how exclusion
      criteria are interpreted.

PMID- 28760537
TI  - Randomized double blind trial of amitriptyline versus placebo in treatment of
      chronic laryngopharyngeal neuropathy.
AB  - OBJECTIVE: A neuropathic etiology has been suggested for patients with chronic
      laryngopharyngitis symptoms without visible structural pathology. Prior studies
      have shown that treatment with neuro-modulating medications is beneficial, but it
      is unknown if this was due to placebo effect. Our objective was to compare the
      efficacy of amitriptyline versus placebo in treating chronic laryngopharyngeal
      neuropathy. STUDY DESIGN: Prospective, randomized placebo-controlled trial.
      METHODS: Patients were randomized to receive placebo or amitriptyline for 8weeks.
      Primary outcome was change in modified Reflux Symptom Index (mRSI) score.
      Secondary outcomes were change in Voice Handicap Index-10 (VHI) scores, rates of
      adverse effects, and overall symptom severity. RESULTS: Eighteen patients
      completed the study. The average difference in mRSI and VHI-10 scores after
      treatment were not significantly different between study arms. However, more
      subjects taking amitriptyline felt their symptoms had subjectively improved (6
      out of 9, 67%), while the remainder noted no change. In the placebo group, only 4
      out of 9 subjects (44%) felt their symptoms were better and 2 felt worse.
      Subjects took an average of 25mg of amitriptyline or placebo daily by the end of
      the 8-week treatment period. No serious adverse effects were noted. CONCLUSION:
      Although there was a trend toward greater subjective improvement in overall
      symptoms with amitriptyline, interpretation is limited due to the small sample
      size. Larger randomized controlled trials to determine the efficacy of neuro
      modulating agents in the treatment of chronic laryngopharyngeal neuropathy, as
      well as better metrics to characterize this disorder, are warranted.

PMID- 28760538
TI  - Schizotypy is associated with reduced mnemonic precision in visual working
      memory.
AB  - BACKGROUND: Working memory (WM) maintains a limited amount of information over a
      short period of time at the service of other ongoing mental activities. Deficits
      in this function are often observed in schizophrenia spectrum disorders. The
      present study examined whether self-report schizotypy was associated with the
      qualitative, quantitative, or both aspects of visual WM and whether these
      impairments could be accounted for by sensory memory deficits and/or depressed
      mood in a group of non-clinical, medication-naive participants. METHOD: Visual WM
      and sensory memory were assessed in 164 medication-naive college students using
      delayed and immediate color estimation tasks, respectively. Self-report measures
      of schizotypy and depressed mood were also collected. RESULTS: Individuals with
      more schizotypal features retained less precise representations in visual WM,
      without a significant reduction in the number of retained WM representations
      (i.e., capacity). In contrast, there was no significant correlation between
      sensory memory precision and schizotypy, suggesting that schizotypy-related
      imprecision in visual WM was unlikely a result of imprecise sensory memory.
      Furthermore, opposite patterns of WM deficits were observed for depressed mood in
      that it was negatively associated with WM capacity, but not with WM precision.
      CONCLUSION: Together, the present findings demonstrated dissociable WM deficits
      in schizotypy and depressed mood, providing strong evidence for unstable mental
      representations in schizotypy and reduced cognitive resource in depressed mood.

PMID- 28760539
TI  - Dissociable auditory mismatch response and connectivity patterns in adolescents
      with schizophrenia and adolescents with bipolar disorder with psychosis: A
      magnetoencephalography study.
AB  - BACKGROUND: There is overlap between schizophrenia and bipolar disorder regarding
      genetic risk as well as neuropsychological and structural brain deficits. Finding
      common and distinct event-response potential (ERP) responses and connectivity
      patterns may offer potential biomarkers to distinguish the disorders. OBJECTIVE:
      To examine the neuronal auditory response elicited by a roving mismatch
      negativity (MMN) paradigm using magnetoencephalography (MEG). PARTICIPANTS: 15
      Adolescents with schizophrenia (ASZ), 16 adolescents with bipolar disorder with
      psychosis (ABP), and 14 typically developing individuals (TD) METHODS: The data
      were analysed using time-series techniques and dynamic causal modelling (DCM).
      OUTCOME MEASURES: MEG difference wave (deviant - standard) at primary auditory
      (~90ms), MMN (~180ms) and long latency (~300ms). RESULTS: The amplitude of
      difference wave showed specific patterns at all latencies. Most notably, it was
      significantly reduced ABP compared to both controls and ASZ at early latencies.
      In contrast, the amplitude was significantly reduced in ASZ compared to both
      controls and ABP. The DCM analysis showed differential connectivity patterns in
      all three groups. Most notably, inter-hemispheric connections were strongly
      dominated by the right side in ASZ only. CONCLUSIONS: Dissociable patterns of the
      primary auditory response and MMN response indicate possible developmentally
      sensitive, but separate biomarkers for schizophrenia and bipolar disorder.

PMID- 28760540
TI  - More sleep? An adaptive response to control pain after traumatic brain injury:
      Comments on article titled "Individuals with pain need more sleep in the early
      stage of mild traumatic brain injury".

PMID- 28760541
TI  - A behavioral intervention for insomnia improves blood pressure.

PMID- 28760542
TI  - How to avoid false positive hyperdense middle cerebral artery sign detection in
      ischemic stroke.
AB  - OBJECTIVES: The aim of the study was to find how to differentiate hyperdense
      middle cerebral artery sign (HMCAS) in stroke patients from asymmetric
      hyperdensity not related to stroke, by comparison of the CT density values
      typical for HMCAS to the values in normal or atherosclerotic middle cerebral
      artery (MCA). METHODS: The group analyzed consisted of 100 patients with ischemic
      stroke, presenting HMCAS on the admission CT. Density measurements in HU were
      performed in the hyperdense segment of the involved MCA, contralateral MCA, brain
      cortex adjacent to the hyperdense MCA. The control group consisted of 100
      patients with no symptoms of cerebral stroke. Density measurements in HU were
      performed: in the M1 segment of right and left MCA, brain cortex adjacent to the
      more dense from right or left MCA. RESULTS: In the stroke group the median values
      obtained were: in the hyperdense MCA 59 HU, contralateral MCA 41 HU, brain cortex
      36 HU. In the control group the median values obtained were: in the more dense
      MCA 43 HU, contralateral MCA 40 HU, brain cortex 34 HU. The range of
      HMCAS/contralateral MCA density ratios in stroke only slightly overlapped the
      range of more dense MCA/contralateral MCA density ratios in non-stroke patients.
      CONCLUSION: The ratio of hyperdense MCA CT density/contralateral density is a
      good tool to differentiate HMCAS from asymmetric hyperdensity not related to
      stroke. The threshold >=1.16 provided 100% sensitivity and 97% specificity,
      whereas >=1.22 provided 94% sensitivity and 100% specificity.

PMID- 28760543
TI  - Hans Selye and the stress response: 80 years after his "letter" to the Editor of
      Nature.

PMID- 28760544
TI  - The potential of Ganoderma lucidum extracts as bioactive ingredients in topical
      formulations, beyond its nutritional benefits.
AB  - Ganoderma lucidum was characterized in terms of nutritional value and chemical
      composition. Thereafter, ethanolic Soxhlet extracts were evaluated for
      antioxidant, anti-inflammatory, antityrosinase, antimicrobial and cytotoxic
      effects, and further characterized in terms of phenolic acids, polysaccharides
      and triterpenoids. Finally, the obtained extracts were tested as cosmeceutical
      ingredients. G. lucidum proved to be a source of macronutrients and important
      bioactive compounds such as terpenoids, specially triterpenoids, and
      polysaccharides. In the extracts, ganoderic acids C2, A and H were the most
      abundant triterpenic acids and protocatechuic, p-hydroxibenzoic and syringic
      acids the identified phenolics. The developed cosmeceutical formulation preserved
      the extract bioactivities, presented a light-yellow colour and a pH of 4.6, which
      is considered appropriate for cosmeceutical's design. Behind the important
      nutritional/bioactive composition of G. lucidum, a potential towards its
      valorisation in the field of cosmeceuticals is foreseeable, as deduced from the
      bioactivities of its ethanolic extract and preservation in the tested
      formulation.

PMID- 28760545
TI  - Reactive carbonyl compounds impair wound healing by vimentin collapse and loss of
      the primary cilium.
AB  - In renal pathologies tubulo-interstitial fibrosis results from an aberrant wound
      healing ability where the normal epithelial tissue is substituted for scar tissue
      caused by accumulation of extracellular matrix proteins (ECM). During the wound
      healing process, epithelial cells may undergo epithelial-mesenchymal transition
      (EMT) acquiring a mesenchymal-like phenotype that allows cells to migrate and re
      epithelialize the wound site. It has been reported that chronic inflammation and
      uremic milieu are involved in wound-healing and enhanced kidney damage in chronic
      kidney disease (CKD) patients. In this study we evaluated reactive carbonyl
      compounds (RCC) effects on renal wound healing. The compounds resulting from
      carbonyl stress evaluated in this study were glyoxal (GO), methylglyoxal (MGO),
      malondialdehyde (MDA) and 4-hydroxy-hexenal (HHE). Wound repair ability was
      evaluated by the wound healing assay using HK-2 cells. EMT was evaluated by
      morphological, protein and transcriptional changes using microscopy, western
      blot, zymography and RT-qPCR. Changes in the vimentin network and primary cilia
      were assessed by immunofluorescence. Our data demonstrated that MDA and GO delay
      wound closure mediated by vimentin disruption, which caused collagen I mRNA
      decrease, and deciliation. In contrast, HHE treatment (and MGO to a minor degree)
      induced morphological changes and increased mesenchymal marker expression and
      gelatinase activity in HK-2 cells. In this study, we have demonstrated for the
      first time that exposure to RCC differentially affects wound healing in proximal
      tubular epithelia. A better comprehension of effects of uremic toxins on wound
      healing and fibrosis and migration is necessary to seek mechanisms to slow down
      renal fibrosis.

PMID- 28760546
TI  - What has been researched about MDR-Candida auris? A bibliometric analysis on the
      'new kid on the block' in hospital-associated infections.

PMID- 28760547
TI  - Controversy in the use of prostate cancer antigen 3 in Latin America and the
      Caribbean.

PMID- 28760548
TI  - Repair of nerve injury by implanting prostheses obtained from isogenic acellular
      nerve segments.
AB  - INTRODUCTION: When a nerve section with a significant gap occurs, it is necessary
      to use a prosthesis to suture it. To date an autologous nerve segment graft
      appears to be the best treatment; but it has several important disadvantages. Our
      goal is to study the effectiveness of an isogenic acellular nerve prosthesis
      comparing a simple suture with tubulisation. MATERIAL AND METHOD: Four groups of
      Wistar rats were used. The animals in Group 0 served as donors of nerve segments
      to graft. Group 1 received the implant with an end-to-end suture. In group 2, the
      implant was sutured inside an E-caprolactone tube. Group 3 received it in a
      polylactic-co-glycolic acid tube. We evaluated the motor function (sciatic index
      and step test in motion), and the regeneration length by histological study of
      regeneration, after a maximum of 3 weeks. RESULTS: Regeneration was uneven in the
      three groups. In all groups, there were implants with regenerated nerve fibres at
      the maximum studied length (15mm) and others where regeneration was scarce. The
      mean regeneration length was greater in the direct end-to-end suture group (G1),
      although the regeneration speed was similar in the three groups. Group 1 showed
      the highest percentage of regeneration, but the variability of results prevents
      this difference reaching statistical significance. We found no significant
      differences between the two groups with polymer tubes. CONCLUSION: For the
      implantation of isogenic acellular nerve prosthesis, under our experimental
      conditions, the direct end-to-end suture was more effective than when it
      isprotected with biopolymer tubes.

PMID- 28760549
TI  - Cognitive deficits in obstructive sleep apnea: Insights from a meta-review and
      comparison with deficits observed in COPD, insomnia, and sleep deprivation.
AB  - Obstructive sleep apnea (OSA) is a nocturnal breathing disorder that is
      associated with cognitive impairment. The primary determinants of cognitive
      deficits in OSA are thought to be sleep disruption and blood gas abnormalities.
      Cognitive impairment is also seen in other disorders that are characterised
      primarily by sleep disturbance (e.g., sleep restriction/deprivation, insomnia) or
      hypoxia/hypercarbia (e.g., chronic obstructive pulmonary disease (COPD)).
      Assessment of the cognitive deficits observed in these other disorders could help
      better define the mechanisms underlying cognitive deficits in OSA. This study
      utilised meta-review methodology to examine the findings from systematic reviews
      and meta-analyses of the effects of untreated OSA, COPD, insomnia, and sleep
      deprivation on cognitive function in adults, compared with norms or controls.
      Eighteen papers met inclusion criteria: seven in OSA, two in insomnia, five in
      COPD, and four in sleep deprivation. OSA and COPD were both accompanied by
      deficits in attention, memory, executive function, psychomotor function, and
      language abilities, suggesting that hypoxia/hypercarbia may be an important
      determinant of deficits in these domains in OSA. Both OSA and sleep deprivation
      studies were accompanied by deficits in attention and memory, suggesting that
      short-term sleep disturbance in OSA may contribute to deficits in these domains.
      Visuospatial deficits were unique to OSA, suggesting the contribution of a
      mechanism other than sleep disturbance and hypoxia/hypercarbia to this problem.
      Our findings suggest that the cognitive deficits associated with untreated OSA
      are multidimensional, with different physiological disturbances responsible for
      differing cognitive problems.

PMID- 28760550
TI  - The role of C/EBPbeta phosphorylation in modulating membrane phospholipids
      repairing in LPS-induced human lung/bronchial epithelial cells.
AB  - Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common
      critical emergency with high mortality in clinical practice. The key mechanism of
      ALI/ARDS is that the excessive inflammatory response damages the integrity of
      alveolar and bronchial cell membrane and thus affects their basic function.
      Phospholipids are the main component of cell membranes. Phospholipase A2 (PLA2),
      which catalyzes the cleavage of membrane phospholipids, is the most important
      inflammatory mediator of ALI. However, clara cell secretory protein 1 (CCSP1), an
      endogenous PLA2 inhibitor can increase the self-defense of membrane
      phospholipids. Thus, CCSP1 up-regulation and PLA2 inhibition constitutes an
      effective method for ensuring the stability of membrane phospholipids and for the
      treatment of ALI/ARDS. In the present study, we developed an in vitro model of
      ALI via lipopolysaccharide (LPS) stimulation of a human bronchial epithelial cell
      line, BEAS-2B, and assessed the mRNA and protein levels of CCSP1 and PLA2 in the
      model cells. The results demonstrated LPS induction inhibited the transcription
      and protein expression of CCSP1, but only the protein level of membrane
      associated PLA2 was increased, suggesting that in the in vitro ALI model,
      abnormally regulated CCSP1 transcription plays a crucial role in the damage of
      cell membrane. To find out the reason that CCSP1 expression was decreased in the
      ALI model, we predicted, by means of bioinformatics, putative transcription
      factors which would bind to CCSP1 promoter, examined their background and
      expression, and found that a transcription factor, CCAAT/enhancer binding protein
      beta (C/EBP beta), was correlated with the transcription of CCSP1 in the in vitro
      ALI model, and its phosphorylation in the model was decreased. CHIP-PCR and
      luciferase reporter assay revealed that C/EBP beta bound to CCSP1 promoter and
      facilitated its transcription. Therefore, we conclude that there is a C/EBP
      beta/CCSP1/PLA2 pathway in the in vitro ALI model. The study of underlying
      mechanism show that the activity of C/EBP beta depends on its phosphorylation:LPS
      stimulation reduced C/EBP beta phosphorylation and suppressed the transcription
      of CCSP1 in BEAS-2B cells, which resulted in enhanced PLA2 and the consequent
      membrane damage. And further study shows that overexpression of
      CDK2(Cyclindependent kinase 2), promoted the phosphorylation of C/EBP beta and
      inhibited PLA2 through the C/EBP beta/CCSP1/PLA2 pathway, so as to attenuate
      membrane damage. The significance of this study lies in that artificial C/EBP
      beta phosphorylation regulation may ease the membrane damage in ALI and improve
      membrane repair.

PMID- 28760551
TI  - Experimental assessment of novel PAX6 splicing mutations in two Chinese families
      with aniridia.
AB  - Aniridia is a rare, congenital ocular disorder caused by the mutations of the
      paired box gene-6 (PAX6) (OMIM 607108), which encodes a highly conserved
      transcriptional regulator. In order to investigate the clinical characterizations
      and genetic defects of two Chinese families affected with aniridia, we recruited
      the family members and 200 ethnically matched controls. The entire exons and
      flanking intronic sequences of the PAX6 gene (NG_008679.1) were analyzed and
      effects of variants on splicing were assessed in silico and in vitro using exon
      trapping assay with pET01. The donor site (c.1183+1G>A) mutation identified in
      family 1 would result in a complete skipping of exon 12 and cause a frameshift
      and run-on translation past the normal termination codon, creating an enlarged
      PAX6 protein with extended COOH-terminal domain. Novel c.1033-1_1033delinsCT
      mutation was detected in family 2. This mutation provoked both complete exon 12
      skipping and partial skipping of exon 12 deleting 7bp. This would lead to a
      frameshift translation and the introduction of pre-mature termination code, which
      resulted in severely truncated PAX6 protein likely to be degraded. Our study
      further expands the spectrum of genetic pathology underlying PAX6.

PMID- 28760552
TI  - CDKN2B-AS may indirectly regulate coronary artery disease-associated genes via
      targeting miR-92a.
AB  - OBJECTIVE: Coronary artery disease (CAD) has a high mortality rate and consists
      of multiple condition, including stable/unstable angina, sudden cardiac death,
      and myocardial infarction. This study is aimed to explore the pathogenesis of
      CAD. METHODS: Datasets of GSE20680 (including 87 CAD samples and 52 normal
      samples) and GSE20681 (including 99 CAD samples and 99 normal samples) were
      obtained from Gene Expression Omnibus database. The differentially expressed
      genes (DEGs) were identified by MetaDE. Effect Sizes in MetaDE package, and then
      were hierarchical clustered using pheatmap package in R. Subsequently, CAD
      associated microRNAs (miRNAs) and their targets were obtained separately by
      miR2Disease and miRTarBase databases, and then used to construct an associated
      miRNA-DEG regulatory network based on BioGRID, HPRD and DIP databases. Enrichment
      analysis was conducted for the involved DEGs using Fisher's exact test, and a
      support vector machine (SVM) classifier was constructed to optimize the feature
      genes. After CAD-associated long non-coding RNAs (lncRNAs) were predicted by
      lncRNA Disease database and their target miRNAs were predicted using miRcode and
      starBase databases, lncRNA-miRNA-DEG regulatory network was constructed. RESULTS:
      Total 1208 DEGs were screened, and 5 CAD-associated miRNAs (including miR-92a)
      were predicted associated with CAD. The SVM classifier was constructed based on
      the 41 featured genes and had high recognition efficiency. Only one lncRNA CDKN2B
      AS targeting miR-92a was obtained. Finally, GATA2, MAP1B and ARG1 were involved
      in the CDKN2B-AS-miR-92a-feature gene regulatory network. CONCLUSION: GATA2,
      MAP1B and ARG1 indirectly regulated by CDKN2B-AS through miR-92a might be
      involved in CAD.

PMID- 28760553
TI  - Genome-wide identification of sweet orange (Citrus sinensis) metal tolerance
      proteins and analysis of their expression patterns under zinc, manganese, copper,
      and cadmium toxicity.
AB  - Plant metal tolerance proteins (MTPs) play important roles in heavy metal
      homeostasis; however, related information in citrus plants is limited. Citrus
      genome sequencing and assembly have enabled us to perform a systematic analysis
      of the MTP gene family. We identified 12 MTP genes in sweet orange, which we have
      named as CitMTP1 and CitMTP3 to CitMTP12 based on their sequence similarity to
      Arabidopsis thaliana MTPs. The CitMTPs were predicted to encode proteins of 864
      to 2556 amino acids in length that included 4 to 6 putative transmembrane domains
      (TMDs). Furthermore, all the CitMTPs contained a highly conserved signature
      sequence encompassing the TMD-II and the start of the TMD-III. Phylogenetic
      analysis further classified the CitMTPs into Fe/Zn-MTP, Mn-MTP, and Zn-MTP
      subgroups, which coincided with the MTPs of A. thaliana and rice. The closely
      clustered CitMTPs shared a similar gene structure. Expression analysis indicated
      that most CitMTP transcripts were upregulated to various extents under heavy
      metal stress. Among these, CitMTP5 in the roots and CitMTP11 in the leaves during
      Zn stress, CitMTP8 in the roots and CitMTP8.1 in the leaves during Mn stress,
      CitMTP12 in the roots and CitMTP1 in the leaves during Cu stress, and CitMTP11 in
      the roots and CitMTP1 in the leaves during Cd stress showed the highest extent of
      upregulation. These findings are suggestive of their individual roles in heavy
      metal detoxification.

PMID- 28760554
TI  - Pathological and gene expression analysis of a polygenic diabetes model,
      NONcNZO10/LtJ mice.
AB  - The NONcNZO10/LtJ mouse is a polygenic model of type-2 diabetes (T2D) that shows
      moderate obesity and diabetes, and is regarded as a good model reflective of the
      conditions of human T2D. In this study, we analyzed pathological changes of
      pancreases with the progress of time by using histopathology and gene expression
      analysis, including microRNA. A number of gene expression changes associated with
      decreased insulin secretion (possibly regulated by miR-29a/b) were observed, and
      zinc homeostasis (Slc30a8, Mt1 and Mt2) or glucose metabolism (Slc2a2) was
      suggested as being the candidate mechanism of pancreas failure in NONcNZO10/LtJ
      mice. These results demonstrate NONcNZO10/LtJ mice have a complex pathogenic
      mechanism of diabetes, and moreover, this fundamental information of
      NONcNZO10/LtJ mice would offer the opportunity for research and development of a
      novel antidiabetic drug.

PMID- 28760555
TI  - Rhythmicity and plasticity of digestive physiology in a euryhaline teleost fish,
      permit (Trachinotus falcatus).
AB  - Digestive physiology is considered to be under circadian control, but there is
      little evidence in teleost fish. The present study explored the rhythmicity and
      plasticity to feeding schedules of enzymatic digestion in a candidate aquaculture
      fish, the permit (Trachinotus falcatus). The first experiment identified the
      rhythms of digestive factors throughout the light-dark (LD) cycle. Gastric
      luminal pH and pepsin activity showed significant daily variation albeit not
      rhythmic. These dynamic changes were likewise observed in several digestive
      enzymes, in which the activities of intestinal protease, chymotrypsin and lipase
      exhibited significant daily rhythms. In the second experiment, the existence of
      feed anticipatory activity in the digestive factors was investigated by
      subjecting the fish to either periodic or random feeding. Anticipatory gastric
      acidification prior to feeding was identified in periodically fed fish. However,
      pepsin activity did not exhibit such anticipation but a substantial postprandial
      increase was observed. Intestinal protease, leucine aminopeptidase and lipase
      anticipated periodic mealtime with elevated enzymatic activities. Plasma
      melatonin and cortisol demonstrated robust daily rhythms but feeding time
      manipulations revealed no significant impact. Plasma ghrelin level remained
      constant during the LD cycle and appeared to be unaffected by differing feeding
      regimes as well. Taken together, the digestive factors of permit were highly
      dynamic during the LD cycle. Periodic feeding entrained digestive physiology and
      mediated anticipatory gastric acidification and intestinal enzymatic activities.
      This knowledge will be essential in developing feeding protocols and husbandry
      related welfare strategies that will further advance this candidate finfish as an
      aquaculture species.

PMID- 28760556
TI  - Bone Scan Index Is an Independent Predictor of Time to Castration-resistant
      Prostate Cancer in Newly Diagnosed Prostate Cancer: A Prospective Study.
AB  - OBJECTIVE: To prospectively determine the prognostic value of the bone scan index
      (BSI) for time to development of castration-resistant prostate cancer (CRPC) in
      consecutive, hormone-naive patients with newly diagnosed prostate cancer.
      PATIENTS AND METHODS: Eligible patients participated in a prospective,
      observational, multicenter study of the value of bone scintigraphy (BS) at
      staging. BSI was determined using the EXINI BoneBSI software in 208 consecutive
      patients undergoing androgen deprivation therapy. The presence or absence of bone
      metastases at staging was classified by BS with or without supplementary imaging.
      Follow-up was performed >5 years after including the last patient. RESULTS:
      During follow-up, 149 of the 208 patients (72%) were diagnosed with CRPC. Median
      time to CRPC was 20 months. Median follow-up time was 4.4 years in patients
      without CRPC. In univariate analyses, presence of bone metastases (M1) (hazard
      ratio [HR] 3.00, 95% confidence interval [CI] 2.10-4.30), Gleason grade (HR 1.53,
      95% CI 1.31-1.79), and BSI (HR 1.17, 95% CI 1.12-1.23) but not PSA significantly
      predicted time to CRPC (all, P < .001). The predictive values of M1 (HR 2.06),
      Gleason grade (HR 1.47), and BSI (HR 1.10) were confirmed in multivariate
      analyses. Log-rank test for equality of time to CRPC showed the significant
      predictive value of BSI (BSI = 0 vs 0 < BSI <= 1 vs BSI > 1, P < .001). In
      addition to routine assessment of M1 vs M0 status, BSI contributed to the
      predictive power. CONCLUSIONS: BSI is an independent risk factor for the time
      from initiation of androgen deprivation therapy to CRPC in hormone-naive
      patients. The significant prognostic factors, in rank order, were M1 status,
      Gleason grade, and BSI.

PMID- 28760557
TI  - Testicular Metastasis From Prostatic Adenocarcinoma Presenting as Recurrent
      Epididymo-orchitis.
AB  - OBJECTIVE: To present a rare case of testicular metastasis from prostatic
      adenocarcinoma origin and to provide a meaningful discussion of currently
      available supporting literature. MATERIALS AND METHODS: Pertinent health
      information was obtained by retrospective analysis of hospital electronic medical
      records. RESULTS: A 93-year-old man with history of castration-resistant
      prostatic adenocarcinoma presented with recurrent episodes of epididymo-orchitis
      with initial symptoms responsive to oral antibiotics. Further investigation with
      testicular ultrasound revealed two 1-cm cystic lesions in the right testicle, one
      complex in nature, with bilateral mild-to-moderate hydroceles. Repeat ultrasound
      confirmed growth of lesions to 1.4 and 1.6 cm, respectively. Patient underwent
      bilateral orchiectomy with resultant symptomatic resolution. Surgical pathology
      returned with an isolated right testicular parenchyma infiltrated by
      adenocarcinoma from a primary prostatic neoplasm. Follow-up at 2 and 8 weeks
      postoperatively revealed prostate-specific antigen levels of 2.60 ng/mL and 4.14
      ng/mL, and with no further complaints of pain. CONCLUSION: The most commonly
      documented sites for metastasis from a prostatic carcinoma origin are to regional
      lymph nodes and bone, followed by the lungs, liver, and adrenal glands. However,
      patients with a history of prostate cancer presenting with recurrent symptoms of
      epididymo-orchitis should have a high suspicion for testicular metastasis.
      Treatment with bilateral orchiectomy offers patients the possibility for both
      favorable symptomatic and oncologic outcomes.

PMID- 28760559
TI  - How to measure responses of the knee to lateral perturbations during gait? A
      proof-of-principle for quantification of knee instability.
AB  - Knee instability is a major problem in patients with anterior cruciate ligament
      injury or knee osteoarthritis. A valid and clinically meaningful measure for
      functional knee instability is lacking. The concept of the gait sensitivity norm,
      the normalized perturbation response of a walking system to external
      perturbations, could be a sensible way to quantify knee instability. The aim of
      this study is to explore the feasibility of this concept for measurement of knee
      responses, using controlled external perturbations during walking in healthy
      subjects. Nine young healthy participants walked on a treadmill, while three
      dimensional kinematics were measured. Sudden lateral translations of the
      treadmill were applied at five different intensities during stance. Right knee
      kinematic responses and spatio-temporal parameters were tracked for the perturbed
      stride and following four cycles, to calculate perturbation response and gait
      sensitivity norm values (i.e. response/perturbation) in various ways. The
      perturbation response values in terms of knee flexion and abduction increased
      with perturbation intensity and decreased with an increased number of steps after
      perturbation. For flexion and ab/adduction during midswing, the gait sensitivity
      norm values were shown to be constant over perturbation intensities,
      demonstrating the potential of the gait sensitivity norm as a robust measure of
      knee responses to perturbations. These results show the feasibility of using the
      gait sensitivity norm concept for certain gait indicators based on kinematics of
      the knee, as a measure of responses during perturbed gait. The current findings
      in healthy subjects could serve as reference-data to quantify pathological knee
      instability.

PMID- 28760560
TI  - Hippocampal dose from stereotactic radiosurgery for 4 to 10 brain metastases:
      Risk factors, feasibility of dose reduction via re-optimization, and patient
      outcomes.
AB  - This study aimed to report hippocampal dose from single-fraction stereotactic
      radiosurgery (SRS) for 4 to 10 brain metastases and determine feasibility of
      hippocampal-sparing SRS. Patients with 4 to 10 brain metastases receiving single
      isocenter, multi-target single-fraction SRS were identified. Hippocampi were
      contoured using the Radiation Therapy Oncology Group (RTOG) 0933 atlas. RTOG 0933
      dose constraints were converted to a biologically effective dose using an
      alpha/beta of 2 (D100 421 cGy, Dmax 665 cGy). Number of metastases, total target
      volume, prescribed dose, and distance of nearest metastasis (dmin) were analyzed
      as risk factors for exceeding hippocampal constraints. If hippocampi exceeded
      constraints, the SRS plan was re-optimized. Key dosimetric parameters were
      compared between original and re-optimized plans. To determine if a single target
      can exceed constraints, all targets but the closest metastasis were removed from
      the plan, and dosimetry was compared. Forty plans were identified. Fifteen
      hippocampi (19%) exceeded constraints in 12 SRS plans. Hippocampal sparing was
      achieved in 10 of 12 replanned cases (83%). Risk factors associated with
      exceeding hippocampal constraints were decreasing dmin (24.0 vs 8.0 mm, p =
      0.002; odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04 to 1.26) and total
      target volume (5.46 cm3vs 1.98 cm3, p = 0.03; OR 1.14, 95% CI 1.00 to 1.32).
      There was no difference in exceeding constraints for 4 to 5 vs 6 to 10 metastases
      (27% vs 21%, p = 0.409) or prescribed dose (18 Gy, p = 0.58). For re-optimized
      plans, there were no significant differences in planning target volume (PTV)
      coverage (99.6% vs 99.0%, p = 0.17) or conformality index (1.47 vs 1.4, p =
      0.78). Six (50%) plans exceeded constraints with a single target. A substantial
      minority of hippocampi receive high radiation dose from SRS for 4 to 10 brain
      metastases. Decreasing distance of the closest metastasis and total target volume
      are associated with exceeding hippocampal constraints. Re-optimizing these plans
      yielded hippocampal-sparing SRS plans with acceptable dosimetry. Prospective
      evaluation of the impact of hippocampal dose from SRS on neurocognition merits
      consideration.

PMID- 28760561
TI  - TRPs and Ca2+ in cell death and survival.
AB  - Transient Receptor Potential (TRP) family mediate the influx of monovalent and/or
      divalent cations into cells in response to environmental stimuli. Pharmacological
      or genetic manipulations of TRP channels demonstrate that TRP channels influence
      cell death rates, prolonging or shortening of cell survival. Due to their diverse
      cellular localization, TRP channels mediated Ca2+ influx generates distinct
      intracellular Ca2+ signals that regulate downstream pathways converging to
      apoptosis or survival. In this review, we summarize the accumulated knowledge
      focused on how TRP channel regulate cell fate and may affect different
      pathologies including cardiovascular, neurological, metabolic or neoplastic
      disorders.

PMID- 28760562
TI  - Corrigendum to "Age at onset of schizophrenia: Cannabis, COMT gene, and their
      interactions" [Volume 151, Issues 1-3, December 2013, Pages 289-290].

PMID- 28760563
TI  - Corrigendum to "Facial, vocal and cross-modal emotion processing in early-onset
      schizophrenia spectrum disorder" [Schizophr. Res. (Aug. 18, 2015) pii: S0920
      9964(15)00405-3. doi: 10. 1016/j.schres.2015.07.039].

PMID- 28760566
TI  - 3-D Virtual Reconstruction of a Large Amniocele With Protrusion of Legs and
      Umbilical Cord Following Asymptomatic Uterine Rupture.
AB  - BACKGROUND: Complete uterine rupture is a rare and severe intrapartum
      complication with high rates of maternal and fetal mortality. Asymptomatic
      uterine rupture is a very rare condition with one unique previous case described
      in the literature. Three-dimensional virtual models allow an immersive virtual
      reality of maternal-fetal structures with better understanding by the parents and
      the medical team. CASE: We demonstrate a case of asymptomatic rupture uterine
      with a large amniocele and protruded legs and umbilical cord at 28 weeks of
      gestation by using a 3-D virtual model from ultrasound scan data. CONCLUSION: 3-D
      virtual models may be applied to the assessment of obstetric complications,
      thereby allowing a novel 3-D spatial view of maternal-fetal structures.

PMID- 28760564
TI  - Junctional delay, frequency, and direction-dependent uncoupling of human
      heterotypic Cx45/Cx43 gap junction channels.
AB  - Gap junction (GJ) channels form low resistance passages between cardiomyocytes
      and play a role in the rapid propagation of action potentials in the heart. A GJ
      channel is formed by two properly docked hemichannels and each hemichannel is a
      hexamer of connexins. Connexin40 (Cx40) and Cx43 are the dominant connexins in
      atrial myocytes, while Cx45 is mostly expressed in the sinoatrial (SA) and
      atrioventricular (AV) nodes which directly connect nodal cells with atrial
      myocytes, possibly via heterotypic Cx40/Cx45 and/or Cx43/Cx45 GJs. However, the
      functional status and channel properties of human heterotypic Cx40/Cx45 or
      Cx43/Cx45 GJs have not been studied. Here we investigated human Cx40/Cx45 and
      Cx43/Cx45 heterotypic GJs by recombinant expression in GJ deficient cells. Unlike
      the finding on rodent connexins, cell pairs expressing human Cx40 in one and Cx45
      in the other failed to form morphological and functional GJs. Modifications in
      human Cx40 with designed variants (D55N or P193Q, but not P193K) are sufficient
      to establish morphological and functional heterotypic GJs with Cx45. In contrast,
      heterotypic human Cx43/Cx45 GJs are functional similar to that described for
      rodent Cx43/Cx45 GJs. Detailed kinetic characterizations of human heterotypic
      Cx43/Cx45 GJs revealed a rapid asymmetric Vj-gating and a much slower recovery,
      which could reduce the GJ conductance in a junctional delay, action potential
      frequency, and direction dependent manner. Dynamic uncoupling in Cx45-containing
      GJs might contribute to a slower action potential propagation in the AV node.

PMID- 28760567
TI  - Canada's Surrogacy Landscape is Changing: Should Canadians Care?

PMID- 28760565
TI  - Familiarity and recollection vs representational models of medial temporal lobe
      structures: A single-case study.
AB  - Although it is known that medial temporal lobe (MTL) structures support
      declarative memory, the fact these structures have different architectonics and
      circuitry suggests they may also play different functional roles. Selective
      lesions of MTL structures offer an opportunity to understand these roles. We
      report, in this study, on JMG, a patient who presents highly unusual lesions that
      completely affected all MTL structures except for the right hippocampus and parts
      of neighbouring medial parahippocampal cortex. We first demonstrate that JMG
      shows preserved recall for visual material on 5 experimental tasks. This finding
      suggests that his right hippocampus is functional, even though it appears largely
      disconnected from most of its MTL afferents. In contrast, JMG performed very
      poorly, as compared to control subjects, on 7 tasks of visual recognition memory
      for single items. Although he sometimes performed above chance, neither
      familiarity nor recollection appeared fully preserved. These results indicate
      that extrahippocampal structures, damaged bilaterally in JMG, perform critical
      operations for item recognition; and that the hippocampus cannot take over that
      role, including recollection, when these structures are largely damaged. Finally,
      in a set of 3 recognition memory tasks with scenes as stimuli, JMG performed at
      the level of control participants and obtained normal indices of familiarity and
      recollection. Overall, our findings suggest that the right hippocampus and
      remnants of parahippocampal cortex can support recognition memory for scenes in
      the absence of preserved item-recognition memory. The patterns of dissociations,
      which we report in the present study, provide support for a representational
      account of the functional organization of MTL structures.

PMID- 28760568
TI  - Bacteria and me: Cell walls, classification, phylogeny and the hidden microbes.

PMID- 28760569
TI  - Jasmonic Acid Oxidase 2 Hydroxylates Jasmonic Acid and Represses Basal Defense
      and Resistance Responses against Botrytis cinerea Infection.
AB  - Jasmonates (JAs) orchestrate immune responses upon wound/herbivore injury or
      infection by necrotrophic pathogens. Elucidation of catabolic routes has revealed
      new complexity in jasmonate metabolism. Two integrated pathways attenuate
      signaling by turning over the active hormone jasmonoyl-isoleucine (JA-Ile)
      through omega-oxidation or deconjugation, and define an indirect route forming
      the derivative 12OH-JA. Here, we provide evidence for a second 12OH-JA formation
      pathway by direct jasmonic acid (JA) oxidation. Three jasmonic acid oxidases
      (JAOs) of the 2-oxoglutarate dioxygenase family catalyze specific oxidation of JA
      to 12OH-JA, and their genes are induced by wounding or infection by the fungus
      Botrytis cinerea. JAO2 exhibits the highest basal expression, and its deficiency
      in jao2 mutants strongly enhanced antifungal resistance. The resistance phenotype
      resulted from constitutive expression of antimicrobial markers rather than from
      their higher induction in infected jao2 plants and could be reversed by ectopic
      expression of any of the three JAOs in jao2. Elevated defense in jao2 was
      dependent on the activity of JASMONATE RESPONSE 1 (JAR1) and CORONATINE
      INSENSITIVE 1 (COI1) but was not correlated with enhanced JA-Ile accumulation.
      Instead, jao2 mutant lines displayed altered accumulation of several JA species
      in healthy and challenged plants, suggesting elevated metabolic flux through JA
      Ile. Collectively, these data identify the missing enzymes hydroxylating JA and
      uncover an important metabolic diversion mechanism for repressing basal JA
      defense responses.

PMID- 28760570
TI  - The Future of Triple Therapy in chronic obstructive pulmonary disease.

PMID- 28760571
TI  - Pulmonary Meningotheliomatosis.

PMID- 28760572
TI  - Kinesiophobia and Its Association With Health-Related Quality of Life Across
      Injury Locations.
AB  - OBJECTIVE: To compare baseline kinesiophobia levels and their association with
      health-related quality of life across injury locations. DESIGN: Retrospective
      cross-sectional study. SETTING: Single, large outpatient physical therapy clinic
      within an academic medical center. PARTICIPANTS: Patients (N=1233) who underwent
      an initial evaluation for a diagnosis related to musculoskeletal pain and
      completed the 11-item version of the Tampa Scale for Kinesiophobia (TSK-11) and
      the Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8) questionnaires
      within 7 days of their first visit were eligible for inclusion. Three hundred
      eighty patients were excluded because of missing data or because they were
      younger than 18 years. A total of 853 patients (mean age, 43.55y; range, 18-94y)
      were included. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Comparison
      of baseline kinesiophobia levels and their association with health-related
      quality of life across injury locations in an outpatient physical therapy
      setting. RESULTS: Separate analysis of variance models compared TSK-11 scores
      based on involved body region, and Pearson correlation coefficients were used to
      examine the association between TSK-11 scores and the SF-8 subscales at each body
      region. TSK-11 scores did not differ by body region (range, 23.9-26.1). Weak to
      moderate negative correlations existed between kinesiophobia and the SF-8
      subscales. CONCLUSIONS: Kinesiophobia levels appear elevated and negatively
      associated with health-related quality of life at initial physical therapy
      evaluation regardless of injury location. These findings suggest that physical
      therapists in outpatient orthopedic settings should implement routine
      kinesiophobia assessment and provide stratified care based on kinesiophobia
      levels across musculoskeletal conditions.

PMID- 28760573
TI  - Work Productivity Loss After Mild Traumatic Brain Injury.
AB  - OBJECTIVES: To examine the completeness of return to work (RTW) and the degree of
      productivity loss in individuals who do achieve a complete RTW after mild
      traumatic brain injury (MTBI). DESIGN: Multisite prospective cohort. SETTING:
      Outpatient concussion clinics. PARTICIPANTS: Patients (N=79; mean age, 41.5y;
      55.7% women) who sustained an MTBI and were employed at the time of the injury.
      Participants were enrolled at their first clinic visit and assessed by telephone
      6 to 8 months postinjury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Structured interview of RTW status, British Columbia Postconcussion Symptom
      Inventory (BC-PSI), Lam Employment Absence and Productivity Scale (LEAPS), Mini
      International Neuropsychiatric Interview, and brief pain questionnaire.
      Participants who endorsed symptoms from >=3 categories with at least moderate
      severity on the BC-PSI were considered to meet International Classification of
      Diseases, 10th Revision criteria for postconcussional syndrome. RTW status was
      classified as complete if participants returned to their preinjury job with the
      same hours and responsibilities or to a new job that was at least as demanding.
      RESULTS: Of the 46 patients (58.2%) who achieved an RTW, 33 (71.7%) had a
      complete RTW. Participants with complete RTW had high rates of postconcussional
      syndrome (44.5%) and comorbid depression (18.2%), anxiety disorder (24.2%), and
      bodily pain (30.3%). They also reported productivity loss on the LEAPS, such as
      "getting less work done" (60.6%) and "making more mistakes" (42.4%). In a
      regression model, productivity loss was predicted by the presence of
      postconcussional syndrome and a comorbid psychiatric condition, but not bodily
      pain. CONCLUSIONS: Even in patients who RTW after MTBI, detailed assessment
      revealed underemployment and productivity loss associated with residual symptoms
      and psychiatric complications.

PMID- 28760574
TI  - Physical Function After Total Knee Replacement: An Observational Study Describing
      Outcomes in a Small Group of Women From China and the United States.
AB  - OBJECTIVE: To describe physical function before and six months after Total Knee
      Replacement (TKR) in a small sample of women from China and the United States.
      DESIGN: Observational. SETTING: Community environment. OUTCOMES: Both groups
      adhered to the Osteoarthritis Research Society International (OARSI) protocols
      for the 6-minute walk and 30-second chair stand. We compared physical function
      prior to TKR and 6 months after using linear regression adjusted for covariates.
      PARTICIPANTS: Women (N=60) after TKR. INTERVENTIONS: Not applicable. RESULTS: Age
      and body mass index in the China group (n=30; 66y and 27.0kg/m2) were similar to
      those in the U.S. group (n=30; 65y and 29.6kg/m2). Before surgery, the China
      group walked 263 (95% confidence interval [CI], -309 to -219) less meters and had
      10.2 (95% CI, -11.8 to -8.5) fewer chair stands than the U.S. group. At 6 months
      when compared with the U.S. group, the China group walked 38 more meters, but
      this difference did not reach statistical significance (95% CI, -1.6 to 77.4),
      and had 3.1 (95% CI, -4.4 to -1.7) fewer chair stands. The China group had
      greater improvement in the 6-minute walk test than did the U.S. group (P<.001).
      CONCLUSIONS: Despite having worse physical function before TKR, the China group
      had greater gains in walking endurance and similar gains in repeated chair stands
      than did the U.S. group after surgery.

PMID- 28760575
TI  - Genotoxicity induced by monomethylarsonous acid (MMA+3) in mouse thymic
      developing T cells.
AB  - Drinking water exposure to arsenic is known to cause immunotoxicity. Our previous
      studies demonstrated that monomethylarsonous acid (MMA+3) was the major arsenical
      species presented in mouse thymus cells after a 30 d drinking water exposure to
      arsenite (As+3). MMA+3 was also showed to be ten times more toxic than As+3 on
      the suppression of IL-7/STAT5 signaling in the double negative (DN) thymic T
      cells. In order to examine the genotoxicity induced by low to moderate doses of
      MMA+3, isolated mouse thymus cells were treated with 5, 50 and 500nMMMA+3 for 18h
      in vitro. MMA+3 suppressed the proliferation of thymus cells in a dose dependent
      manner. MMA+3 at 5nM induced DNA damage in DN not double positive (DP) cells.
      Differential sensitivity to double strand breaks and reactive oxygen species
      generation was noticed between DN and DP cells at 50nM, but the effects were not
      seen at the high dose (500nM). A stronger apoptotic effect induced by MMA+3 was
      noticed in DN cells than DP cells at low doses (5 and 50nM), which was negated by
      the strong apoptosis induction at the high dose (500nM). Analysis of
      intracellular MMA+3 concentrations in DN and DP cells, revealed that more MMA+3
      accumulated in the DN cells after the in vitro treatment. Collectively, these
      results suggested that MMA+3 could directly induce strong genotoxicity in the
      early developing T cells in the thymus. The DN cells were much more sensitive to
      MMA+3 induced genotoxicity and apoptosis than DP cells, probably due to the
      higher intracellular levels of MMA+3.

PMID- 28760576
TI  - Performances and Limitations of Several Ultrasound-Based Elastography Techniques:
      A Phantom Study.
AB  - The objective of this study is to assess strain and shear wave (SW) elastography
      performance in terms of accuracy by performing in vitro measurements on a
      calibrated elastography phantom. Acquisitions were done on a phantom containing 4
      inclusions (12-74 kPa) embedded in a homogeneous background material (30 kPa). We
      performed qualitative assessment on elastograms, semiquantitative assessment with
      strain or elasticity ratios between each inclusion and the background and
      quantitative evaluation with SW acquisitions. Ratio and elasticity estimations
      were compared with expected values. Biases, relative errors and 95% confidence
      intervals (95% CI) were calculated. All techniques adequately classified
      inclusions as harder or softer than the background. For stiffness ratio
      estimation, SW methods were more precise than strain methods and had
      significantly higher percentages of correctly classified measurements (p =
      0.008). Quantitative stiffness measurements were reproducible despite constant
      biases. SW elastography methods provide more reproducible estimations of tissue
      stiffness ratio than strain methods, as well as reproducible quantitative tissue
      stiffness despite constant biases.

PMID- 28760577
TI  - Longitudinal assessment of interstitial pneumonia with autoimmune features is
      encouraged.

PMID- 28760578
TI  - Pre-birth origins of allergy and asthma.
AB  - Allergy is a chronic disease that can develop as early as infancy, suggesting
      that early life factors are important in its aetiology. Variable associations
      between size at birth, a crude marker of the fetal environment, and allergy have
      been reported in humans and require comprehensive review. Associations between
      birth weight and allergy are however confounded in humans, and we and others have
      therefore begun exploring the effects of early life events on allergy in
      experimental models. In particular, we are using ovine models to investigate
      whether and how a restricted environment before birth protects against allergy,
      whether methyl donor availability contributes to allergic protection in IUGR, and
      why maternal asthma during pregnancy is associated with increased risks of
      allergic disease in children. We found that experimental intrauterine growth
      restriction (IUGR) in sheep reduced cutaneous responses to antigens in progeny,
      despite normal or elevated IgE responses. Furthermore, maternal methyl donor
      supplementation in late pregnancy partially reversed effects of experimental
      IUGR, consistent with the proposal that epigenetic pathways underlie some but not
      all effects of IUGR on allergic susceptibility. Ovine experimental allergic
      asthma with exacerbations reduces relative fetal size in late gestation, with
      some changes in immune populations in fetal thymus suggestive of increased
      activation. Maternal allergic asthma in mice also predisposes progeny to allergy
      development. In conclusion, these findings in experimental models provide direct
      evidence that a perturbed environment before birth alters immune system
      development and postnatal function, and provide opportunities to investigate
      underlying mechanisms and develop and evaluate interventions.

PMID- 28760579
TI  - Survival of iPSC-derived grafts within the striatum of immunodeficient mice:
      Importance of developmental stage of both transplant and host recipient.
AB  - Degeneration of the striatum can occur in multiple disorders with devastating
      consequences for the patients. Infantile infections with streptococcus, measles,
      or herpes can cause striatal necrosis associated with dystonia or dyskinesia; and
      in patients with Huntington's disease the striatum undergoes massive
      degeneration, leading to behavioral, psychological and movement issues,
      ultimately resulting in death. Currently, only supportive therapies are available
      for striatal degeneration. Clinical trials have shown some efficacy using
      transplantation of fetal-derived primary striatal progenitors. Large banks of
      fetal progenitors that give rise to medium spiny neurons (MSNs), the primary
      neuron of the striatum, are needed to make transplantation therapy a reality.
      However, fetal tissue is of limited supply, has ethical concerns, and is at risk
      of graft immunorejection. An alternative potential source of MSNs is induced
      pluripotent stem cells (iPSCs), adult somatic tissues reprogrammed back to a stem
      cell fate. Multiple publications have demonstrated the ability to differentiate
      striatal MSNs from iPSCs. Previous publications have demonstrated that the
      efficacy of fetal progenitor transplants is critically dependent upon the age of
      the donor embryo/fetus as well as the age of the transplant recipient. With the
      advent of iPSC technology, a question that remains unanswered concerns the
      graft's "age," which is crucial since transplanting pluripotent cells has an
      inherent risk of over proliferation and teratoma formation. Therefore, in order
      to also determine the effect of transplant recipient age on the graft, iPSCs were
      differentiated to three stages along a striatal differentiation paradigm and
      transplanted into the striatum of both neonatal and adult immunodeficient mice.
      This study demonstrated that increased murine transplant-recipient age (adult vs
      neonate) resulted in decreased graft survival and volume/rostro-caudal spread
      after six weeks in vivo, regardless of "age" of the cells transplanted.
      Importantly, this study implicates that the in vivo setting may provide a better
      neurogenic niche for iPSC-based modeling as compared to the in vitro setting.
      Together, these results recapitulate findings from fetal striatal progenitor
      transplantation studies and further demonstrate the influence of the host
      environment on cellular survival and maturation.

PMID- 28760580
TI  - Landscape scale heterogeneity in the East Turkana ecosystem during the Okote
      Member (1.56-1.38 Ma).
AB  - Placing the biological adaptations of Pleistocene hominins within a well-resolved
      ecological framework has been a longstanding goal of paleoanthropology. This
      effort, however, has been challenging due to the discontinuous nature of
      paleoecological data spanning many important periods in hominin evolution.
      Sediments from the Upper Burgi (1.98-1.87 Ma), KBS (1.87-1.56 Ma) and Okote (1.56
      1.38 Ma) members of the Koobi Fora Formation at East Turkana in northern Kenya
      document an important time interval in the evolutionary history of the hominin
      genera Homo and Paranthropus. Although much attention has been paid to Upper
      Burgi and KBS member deposits, far less is known regarding the East Turkana
      paleoecosystem during Okote Member times. This study pairs spatially-resolved
      faunal abundance data with stable isotope geochemistry from mammalian enamel to
      investigate landscape-scale ecosystem variability during Okote Member times. We
      find that during this period 1) taxa within the East Turkana large mammal
      community were distributed heterogeneously across space, 2) the abundance of C3
      and C4 vegetation varied between East Turkana subregions, and 3) the Karari
      subregion, an area with abundant evidence of hominin stone tool manufacture, had
      significantly more C3 vegetation than regions closer to the central axis of the
      Turkana Basin (i.e., Ileret and Koobi Fora). These findings indicate that the
      East Turkana paleoecosystem during the Okote Member was highly variable across
      space and provided a complex adaptive landscape for Pleistocene hominins.

PMID- 28760581
TI  - Any nonadherence to instructions for use predicts graft-related adverse events in
      patients undergoing elective endovascular aneurysm repair.
AB  - BACKGROUND: A variety of devices exist for endovascular aneurysm repair (EVAR).
      Device-specific instructions for use (IFU) detail anatomic constraints to
      application and deployment of devices and are developed from rigorous bench
      testing. Nonadherence to IFU occurs frequently to avoid open surgery. The purpose
      of this study was to determine if IFU violations are associated with increased
      risk of graft-related adverse events (GRAEs) during follow-up. METHODS: This
      multicenter retrospective observational study included patients undergoing
      elective endovascular repair for abdominal aneurysmal disease with three
      different devices. Demographics, anatomic data, and follow-up data were collected
      on patients from 2005 to 2014. IFU violations were device specific and included
      neck diameter, length, and angulation and iliac artery diameter and length. GRAEs
      included a composite outcome of reintervention, migration, endoleak (type II
      excluded), rupture, limb occlusion, sac growth, and aneurysm-related mortality
      during the follow-up period. Kaplan-Meier survival and Cox proportional hazards
      modeling were performed. Any IFU violations as well as neck-specific IFU
      violations were analyzed. RESULTS: In 461 patients undergoing EVAR, 43.8% had at
      least one IFU violation. Patients with IFU violations were more likely to have
      peripheral vascular disease (12.4% vs 7.3%) and were less likely to be male
      (78.7% vs 90.3%). The most frequent IFU violations included diameter deviations
      of the neck (15.2%) and of the iliac artery (21.4%). Overall, the GRAE rate was
      12.8%. Median follow-up time was 1.9 and 2.1 years for patients with and without
      an IFU violation, respectively. Kaplan-Meier survival revealed a significant
      association between the presence of an IFU violation and GRAEs (log-rank, P =
      .031). When adjusted for clinical variable through Cox hazard modeling, the
      association remained significant (hazard ratio 1.8; 95% confidence interval, 1.05
      3.1). When neck-specific violations were considered independently, Kaplan-Meier
      survival (log-rank, P = .003) and Cox modeling (hazard ratio, 2.2; 95% confidence
      interval, 1.2-4.0) revealed a significant association between neck-specific IFU
      violation and GRAEs. CONCLUSIONS: A total of 43.8% of patients undergoing EVAR
      had a device-specific IFU violation, indicating that implanters are pushing the
      boundaries of device capabilities. Our study identified that any IFU violation
      was significantly associated with GRAEs over time. Caution should be applied to
      patients being considered for EVAR when IFU deviations exist.

PMID- 28760582
TI  - Improved outcomes with proximal radial-cephalic arteriovenous fistulas compared
      with brachial-cephalic arteriovenous fistulas.
AB  - BACKGROUND: Brachial-cephalic arteriovenous fistulas (BCFs) are associated with
      high-flow volumes, leading to potential risks such as arm swelling, steal
      syndrome, pseudoaneurysm (due to a pressurized access), and cephalic arch
      stenosis. We hypothesized that a proximal radial-cephalic fistula (prRCF)
      configuration mitigates these risks because a lower flow state is created.
      Furthermore, we also hypothesized that despite these lower flows, patencies
      (primary, primary assisted, secondary) are sustained. METHODS: Leveraging a
      prospectively collected database supplemented with detailed medical record data,
      analyses of patients undergoing BCF and prRCF were completed (November 2008
      through March 2016). Preoperative clinical and imaging characteristics, operative
      variables, and postoperative complications were reviewed. The primary end point
      was a composite of arm swelling, steal, and pseudoaneurysm at 2 years.
      Fistulograms and interventions (surgical revision, thrombectomy, endovascular
      treatment of cephalic arch stenosis) censored at 2 years were compared between
      configurations. Patencies were plotted using Kaplan-Meier techniques and compared
      using Cox proportional hazards. RESULTS: During the study period, 345
      arteriovenous fistulas and 72 prosthetic grafts were primarily placed; 56
      patients underwent BCF and 50 patients underwent prRCF with a mean follow-up of
      1.8 +/- 1.7 (standard deviation) years. Except for prRCF patients being older,
      there was no difference between the groups with regard to preoperative
      characteristics. The artery diameter used for anastomosis was significantly
      larger in the BCF group (4.0 +/- 1.1 mm vs 2.6 +/- 0.8 mm; P < .001), with higher
      flow volumes at 6-week ultrasound examination (1060 +/- 587 mL/min vs 735 +/- 344
      mL/min; P < .001). Complications (arm swelling, steal, pseudoaneurysm) were
      significantly more common in the BCF group (P = .02). There was a trend, albeit
      statistically insignificant, for the BCF group to require more cephalic arch
      stenosis interventions. Of those patients needing dialysis within 1 year, both
      BCF and prRCF were successfully used in the majority of patients (n = 27 [66%] vs
      n = 25 [63%]; P = 1.0). Unadjusted and adjusted primary, primary assisted, and
      secondary patency rates were similar between the groups. CONCLUSIONS: prRCFs have
      fewer complications yet similar midterm durability compared with BCFs. When it is
      anatomically feasible, prRCFs should be constructed over BCFs because of their
      superior physiology and clinical outcomes.

PMID- 28760583
TI  - Discussion.

PMID- 28760585
TI  - Key factors for hand hygiene promotion in intensive care units.

PMID- 28760584
TI  - The endothelial cell secretome as a novel treatment to prime adipose-derived stem
      cells for improved wound healing in diabetes.
AB  - BACKGROUND: Chronic wounds are a common surgical problem exacerbated by diabetes
      and ischemia. Although adipose-derived stem cells (ASCs) have shown promise as a
      wound healing therapy, their function and proliferation are hindered in diabetes.
      This study examines the ability of the human umbilical vein endothelial cell
      (HUVEC) secretome to reverse the deleterious effects of high glucose
      concentrations on ASCs through priming, thereby enhancing their ability to
      participate in angiogenesis and wound healing. METHODS: Institutional review
      board-approved human ASCs were cultured in M199 medium with or without glucose
      (30 mmol/L). HUVEC were grown in 30 mmol/L glucose-containing M199 medium; the
      resulting conditioned medium (HUVEC-CM) was collected every 3 days and used to
      prime ASCs. An aliquot of HUVEC-CM was heated (85 degrees C for 30 minutes) to
      produce thermal denaturation of protein. Viability, proliferation, and
      endothelial differentiation were measured by MTT assays, growth curves, and
      quantitative polymerase chain reaction, respectively. A Matrigel assay was used
      to assess the ability of primed ASCs to participate in capillary-like tube
      formation. An Institutional Animal Care and Use Committee-approved in vivo murine
      model of diabetic and ischemic hindlimbs was used to evaluate the angiogenic
      potential of primed stem cells. Human ASCs were cultured with either control M199
      or HUVEC-CM. Mice were randomized to a control group, an unprimed ASC group, or a
      HUVEC-primed ASC group. Cellular therapies were injected into the ischemic
      muscle. Thirty days later, slides were made. Microvessels were counted by three
      blinded observers. RESULTS: MTT assays revealed that HUVEC-priming induced a 1.5
      times increase in cell viability over diabetic controls. This promoting effect
      was lost with heated HUVEC-CM (P < .001), indicating that the active molecules
      are of protein origin. After 9 days, ASCs cultured in 30 mmol/L glucose solution
      showed a 14% reduction in growth from nondiabetic controls (P = .013) and
      exhibited atrophic morphology. Conversely, diabetic HUVEC-primed stem cells
      demonstrated a nearly four-fold increase in proliferation (P < .05) and took on a
      fusiform, endothelial-like phenotype. Polymerase chain reaction demonstrated
      enhanced expression of CD31 messenger RNA by 4.7-fold after 14 days in the HUVEC
      primed group, and endothelial nitric oxide synthase messenger RNA messenger RNA
      was increased 20.1-fold from controls. Unlike unprimed controls, HUVEC-primed
      ASCs readily formed capillary-like tube networks on Matrigel. Diabetic mice that
      were injected with HUVEC-primed ASCs demonstrated greater vessel density than
      both controls (2.1-fold) and unprimed stem cell treatments (P < .001).
      CONCLUSIONS: HUVECs secrete protein factors that significantly increase
      proliferation and endothelial differentiation of ASCs under diabetic conditions.
      Injection of ischemic hindlimbs in diabetic mice with HUVEC-primed ASCs leads to
      enhanced angiogenesis.

PMID- 28760586
TI  - Inactivation of microbicidal active halogen compounds by sodium thiosulphate and
      histidine/methionine for time-kill assays.
AB  - Rapid inactivation of antimicrobial test agents after exact incubation times with
      microorganisms is required in time-kill assays. Sodium thiosulphate and a
      combination of methionine and histidine were compared for neutralisation of
      active halogen compounds. Test oxidants were mixed with surplus sodium
      thiosulphate (3%-6%) or histidine/methionine (1% each) in phosphate-buffered
      saline and incubated for different times, followed by addition of Staphylococcus
      aureus, Escherichia coli, or Pseudomonas aeruginosa at 1000CFU/ml. After further
      incubation, quantitative cultures were performed. Thiosulphate did not
      sufficiently inactivate chlorine and bromine compounds, indicated by a 10-fold
      (S. aureus) up to >100-fold (E. coli, P. aeruginosa) reduction of CFU. This was
      particularly true for high concentrations of the oxidants of about 50mM, for
      highly reactive agents (HOCl and bromamine T) more than for chloramine T and N
      chlorotaurine, and for short pre-incubation times before addition of the
      bacteria. By contrast, histidine/methionine proved to be suitable for chloramines
      and bromamine T and for low concentrations of HOCl (0.07%). HOCl at 0.7% could
      neither be inactivated completely by thiosulphate nor by histidine/methionine. In
      contrast to chlorine and bromine compounds, iodine was neutralized by
      thiosulphate, but not by histidine/methionine. Histidine/methionine is superior
      to inactivate chlorine and bromine and should replace sodium thiosulphate at
      least in killing tests with high concentrations of these disinfectants. Inclusion
      of a short reaction time (maximum one minute) of test oxidant and neutralising
      substance before addition of bacteria is decisive in inactivation tests to obtain
      reliable results.

PMID- 28760587
TI  - Effects of microplastics on sessile invertebrates in the eastern coast of
      Thailand: An approach to coastal zone conservation.
AB  - This study assessed the microplastic contamination of 3 most abundant sessile and
      intertidal invertebrates (Rock Oyster: Saccostrea forskalii, Striped Barnacle:
      Balanus amphitrite, Periwinkle: Littoraria sp.) in 3 beaches of the eastern
      coasts of Thailand. The results showed a significant accumulation of
      microplastics in the invertebrates at rates of 0.2-0.6 counts/g indicating higher
      pollution levels along the coastline. Filter feeding organisms showed
      comparatively higher accumulation rates of microplastics. Thus, contaminated
      bivalves pose potential health risks for seafood consumers. The plastic pollutant
      prevalence in sessile and intertidal communities was corresponded with pollution
      characteristics of contaminated beach habitats where they live. Thus, bivalves,
      gastropods and barnacles can be used as indicators for contamination of
      microplastics in the areas. This study also demonstrated the need for controlling
      plastic pollution in Thai coastal areas.

PMID- 28760588
TI  - Contamination and ecological risk assessment of trace elements in sediments of
      the rivers of Sundarban mangrove forest, Bangladesh.
AB  - In this study, total concentrations of 16 trace elements (Al, V, Cr, Mn, Fe, Co,
      Ni, Cu, Zn, As, Cd, Sb, Hg, Pb, Th and U) in sediments of the rivers of the
      Sundarban mangrove forest, after the catastrophic oil spill accident in the Sela
      river of Sundarban, were determined. The overall mean concentrations of V, Cr, Fe
      and Cd in surface sediments of the Sundarban are remarkably higher than available
      literature data of those elements. Trace element contamination assessment, using
      different environmental contamination indices, reveals that As, Sb, Th and U are
      low to moderately contaminated while Cd is moderately to severely contaminated in
      the sediments of this area. The multivariate statistical analyses were applied to
      reveal the origin and behavior of the elements during their transport in the
      mangrove ecosystem. High Cr, Ni, Cu and As concentrations suggest the risk of
      potentially adverse biological effects in the ecosystem.

PMID- 28760589
TI  - Can we assess the ecological status of estuaries based on larval fish
      assemblages?
AB  - Fish larvae of four SE Brazilian estuaries were investigated to assess if the
      larval fish assemblages reflect the ecological status of estuaries. All samples
      were collected in the same water mass to guarantee similar natural water
      parameters, assuring that major differences among estuaries were related to
      anthropogenic pressures. Water temperature, oxygen, pH, chlorophyll a, faecal
      coliforms, nutrient load and total particulate matter were obtained at each
      sampling area. A pressure index was used to assess the overall anthropogenic
      pressures acting in each estuary. Results showed that fish larvae were sensitive
      to water contamination, reducing the diversity and especially exhibiting a high
      dominance of few species. Furthermore, this study reinforced the idea that the
      high sensitivity of fish larvae can increase the accuracy of the environmental
      assessments when tackling short-time events of hydrological controls (physical
      barriers and control of the freshwater input), representing an advance in the
      water ecological quality assessments.

PMID- 28760590
TI  - Comparison of vaginal ointment of honey and clotrimazole for treatment of
      vulvovaginal candidiasis: A random clinical trial.
AB  - BACKGROUND AND OBJECTIVE: Vulvovaginal candidiasis (VVC) is the most prevalent
      vaginitis in women, accounting for 10 million medical referrals a year. Vaginal
      clotrimazole is a drug of choice for VVC treatment. However, increased drug
      resistance to this microorganism has led to an interest in naturally derived
      antifungal drugs. This study was conducted to compare honey vaginal ointment and
      clotrimazole vaginal ointment for VVC treatment. METHODS: Eighty women diagnosed
      with VVC were assigned to two groups for honey ointment and clotrimazole ointment
      treatment using a simple randomization rule. The ointments were applied at night
      for seven days. The disease symptoms including inflammation, vaginal discharge,
      and irritation at baseline in the fourth and eighth days of treatment were
      examined and compared between the two groups. The data was analyzed by SPSS
      version 20 with the Friedman test, Chi-square test, and independent t-test.
      P<0.05 was considered as the significance. RESULTS: The two groups were similar
      for inflammation severity, irritation, and discharge at baseline. In both the
      groups, the symptoms disappeared after treatment. On the eighth day of treatment,
      there was a significant difference in inflammation and vaginal discharge between
      the two groups. Inflammation (P=0.002) and vaginal discharge (P=0.003) recovered
      better in the clotrimazole group. But there was no significant difference in
      irritation severity and satisfaction with treatment between the two groups. In
      the two groups, no side effects were reported. CONCLUSION: Honey contributes to
      treating VVC. Thanks to the popular positive attitudes of honey, its
      availability, no need for sterility, and its cost-effectiveness, it is a choice
      of treatment for VVC.

PMID- 28760591
TI  - The hairy lizard: heterothermia affects anaesthetic requirements in the Arabian
      oryx (Oryx leucoryx).
AB  - OBJECTIVE: To study the effect of heterothermia on anaesthetic drug requirements
      in semi-free ranging Arabian oryx and to assess the temperature quotient (Q10) of
      oxygen consumption. STUDY DESIGN: Prospective observational study and controlled
      metabolic experiment. ANIMALS: Sixty-eight anaesthetic events in 59 Arabian oryx
      from Mahazat As-Sayd protected area, Saudi Arabia METHODS: Anaesthesia was
      induced by remote injection of 25 mg ketamine, 10 mg midazolam and 0.5 mg
      medetomidine with a variable amount of etorphine based on a target dosage of 20
      MUg kg-1 and subjective assessment of body mass. Animals not recumbent within 15
      minutes or insufficiently anaesthetized were physically restrained and
      administered supplementary etorphine intravenously depending on the anaesthetic
      depth. Body temperature (Tb) was measured rectally immediately upon handling of
      each animal. From six anaesthetized oryx, expiratory gasses for oxygen analysis
      and metabolic rate calculation were collected at two Tbs; before and after
      submersion in ice water for approximately 30 minutes. RESULTS: Forty-two animals
      (62%) became recumbent with the initial dose, with a mean induction time (+/-
      standard deviation) of 9 +/- 2 minutes. The remaining animals could be handled
      but needed 0.3 +/- 0.1 mg etorphine intravenously to reach the desired level of
      anaesthesia. There was a significant positive correlation between Tb and
      effective etorphine dosage (R2 = 0.48, p < 0.0001). Average Tb of the six animals
      in which metabolic rate was measured decreased from 40.0 +/- 0.5 degrees C
      immediately after induction to 35.5 +/- 0.5 degrees C after cooling. This
      reduction was associated with a reduction in oxygen uptake from 3.11 +/- 0.33 to
      2.22 +/- 0.29 mL O2 minute-1 kg-1, reflected in Q10 of 2.17 +/- 0.14. CONCLUSIONS
      AND CLINICAL RELEVANCE: Tb significantly affects anaesthetic requirements in
      Arabian oryx and should be considered when selecting dosages for anaesthetic
      induction for species showing diurnal heterothermy.

PMID- 28760592
TI  - Promising rodent models in Parkinson's disease.
AB  - BACKGROUND: In the past decade, the study of the pathogenic mechanisms underlying
      neurodegeneration in Parkinson's disease (PD) has revealed a genetic component,
      often associated with a number of environmental risk factors. Animal models have
      improved our understanding of disease pathogenesis, providing significant
      insights into the understanding of novel molecular pathways. Each model has its
      own specific features and limitations, and the choice of the most appropriate one
      depends on the specific question that has to be answered. AIM: To provide an
      overview of some of the models supporting the hypothesis that early synaptic
      dysfunction represents a central event in the course of the disease. DEVELOPMENT:
      Along with "classical" models, based on the administration of neurotoxins and
      capable of replicating the neuropathological hallmarks of the disease, a number
      of genetic models, reproducing the disease-causing mutations of monogenic forms
      of familial PD, have been generated. More recently, novel models have been
      developed, based on the combination of a toxic insult together with PD mutations,
      allowing for the identification of dysfunction at a prodromal disease stage.
      CONCLUSIONS: The development and characterization of new models is crucial for a
      better understanding of PD related-synaptopathy, and hold promise for the
      identification of novel therapeutics.

PMID- 28760593
TI  - Integration of technology-based outcome measures in clinical trials of Parkinson
      and other neurodegenerative diseases.
AB  - INTRODUCTION: We sought to review the landscape of past, present, and future use
      of technology-based outcome measures (TOMs) in clinical trials of
      neurodegenerative disorders. METHODS: We systematically reviewed PubMed and
      ClinicalTrials.gov for published and ongoing clinical trials in neurodegenerative
      disorders employing TOMs. In addition, medical directors of selected
      pharmaceutical companies were surveyed on their companies' ongoing efforts and
      future plans to integrate TOMs in clinical trials as primary, secondary, or
      exploratory endpoints. RESULTS: We identified 164 published clinical trials
      indexed in PubMed that used TOMs as outcome measures in Parkinson disease (n =
      132) or other neurodegenerative disorders (n = 32). The ClinicalTrials.gov search
      yielded 42 clinical trials using TOMs, representing 2.7% of ongoing trials.
      Sensor-based technology accounted for over 75% of TOMs applied. Gait and physical
      activity were the most common targeted domains. Within the next 5 years, 83% of
      surveyed pharmaceutical companies engaged in neurodegenerative disorders plan to
      deploy TOMs in clinical trials. CONCLUSION: Although promising, TOMs are
      underutilized in clinical trials of neurodegenerative disorders. Validating
      relevant endpoints, standardizing measures and procedures, establishing a single
      platform for integration of data and algorithms from different devices, and
      facilitating regulatory approvals should advance TOMs integration into clinical
      trials.

PMID- 28760594
TI  - S-oxiracetam protect against ischemic stroke via alleviating blood brain barrier
      dysfunction in rats.
AB  - The blood brain barrier (BBB) maintains the basic stability of the brain tissue
      under physiological conditions, while destroys and exaggerates brain edema and
      inflammatory response after ischemic stroke. In this study, we researched S
      oxiracetam (S-ORC), a nootropic drug, alleviates BBB dysfunction and protects
      against ischemic stroke in rats. Middle cerebral artery
      occlusion(MCAO)/reperfusion in rats is applied to mimic ischemic stroke. One hour
      after reperfusion, rats are administered intravenously with different dose (0.12,
      0.24, or 0.48g/kg) of S-ORC for continuative three days. Seventy-two hours after
      MCAO, TTC staining, hematoxylin and eosin (H&E) staining, brain water content,
      immunohistochemical staining, EB extravasation, western blot are provided to
      evaluate the protective effect and possible mechanism of S-ORC on BBB
      dysfunction. Furthermore, brain concentration of verapamil (P-glycoprotein
      substrate) and atenolol (paracellular transport marker) were assayed by UPLC
      MS/MS co administration with or without S-ORC. The results show that post
      treatment of S-ORC decreases cerebral infarct size, lessens brain edema, inhibits
      neutrophil infiltration and cytokines releasing. Furthermore, S-ORC treatment
      decreases EB leakage, downregulates MMP-9, upregulates occludin and claudin-5,
      and decreases brain concentration of verapamil and atenolol after MCAO surgery.
      In conclusion, the present study demonstrates that post-treatment of S-ORC
      alleviates BBB dysfunction by regulating tight junction proteins (TJPs),
      upregulating P-glycoprotein function, and protects against ischemic stroke as
      result.

PMID- 28760595
TI  - [Smoking and blood pressure: A complex relationship].
AB  - Hypertension and tobacco smoking are two major modifiable risk factors for
      atheromatous disease and its cardiovascular complications. If systolic
      hypertension (SBP>=140mmHg and DBP<90mmHg) is the leading risk factor for stroke,
      smoking (nicotine) has a more powerful impact on coronary events, aortic
      aneurysms, and peripheral artery disease. Smoking can transiently modify the
      regulation of blood pressure (BP) by a swift effect on the autonomic nervous
      system. It also accelerates arterial aging, which plays a role in chronic
      hypertension. Chronic sympathetic activation induced by tobacco smoking also has
      some involvement in lipid metabolism and insulin resistance, both implicated in
      atheromatous disease. Thus, smoking can contribute to the development of
      atheromatous renal artery stenosis, which is an aggravating cause of
      hypertension. It may also reduce the effectiveness of most antihypertensive
      drugs. Finally, it is often associated with increased alcohol consumption. All
      these factors may contribute to poor blood pressure control in these high-risk CV
      patients. Smoking cessation is effective regardless of patient age and length of
      consumption. Every effort should thus be made to support smoking cessation. This
      is the objective of the French "Plan Sans Tabac" (No Tobacco Plan) and the
      related actions conducted by the French Federation of Cardiology.

PMID- 28760596
TI  - Serum resistin levels inversely associated with cardiovascular risk indices in
      type 2 diabetics from central Mexico.
AB  - AIMS: Since, resistin has been associated with coronary heart disease and with
      the progression of Type 2 Diabetes (T2D), our objective was to determine the
      correlation between resistin and cardiovascular risk (CVR) in subjects with
      increasing degrees of hyperglycemia. METHODS: Using a cross-sectional study
      design, the anthropometric and biochemical profiles were collected from 180
      subjects from Puebla, Mexico. Subjects were separated into Normoglycemic (NGT),
      pre-diabetic (PT2D), or T2D. CVR was determined by the Atherosclerosis
      Coefficient ((total cholesterol-high-density lipoprotein)/high-density
      lipoprotein), Castelli 1 index (total cholesterol/high-density lipoprotein),
      Castelli 2 index (low-density lipoprotein/high-density lipoprotein), Framingham
      risk score (https://www.mdcalc.com/framingham-coronary-heart-disease-risk
      score#next-steps), and the CVR index (CVRI=triglyceride/high-density
      lipoprotein). Differences between groups were determined using ANOVA. Partial
      correlation assessed the association between resistin and CVR indices. Logistic
      regression was used to determine the risk [Odds ratio (OR)] between resistin and
      CVR. RESULTS: Serum Resistin levels were similar between NGT, PT2D, and T2D. No
      correlation was observed between resistin and CVR indices for the NGT and PT2D.
      However, T2D demonstrated a strong negative association between the Framingham
      (r=-0.34, p=0.01), the Castelli 1 index (r=-0.29, p<0.01), and the CVRI (r=-0.38,
      p<0.05), when adjusted for sex and taking treatment for T2D. For T2D, when the
      subjects were separated by resistin into tertiles, elevated resistin was
      associated with a benefit for the Castelli 1 index (T1 v T3: OR=0.15, 95% CI:
      0.03-0.070) and the CVRI (T1 v T3: OR=0.13, 95% CI: 0.03-0.66). CONCLUSIONS:
      Here, we demonstrate that, for T2D, elevated resistin levels lowered the CVR in
      Mexicans.

PMID- 28760598
TI  - Multipurpose Prevention Technologies: A Global Sexual and Reproductive Health
      Priority.

PMID- 28760597
TI  - Human and Plasmodium serine hydroxymethyltransferases differ in rate-limiting
      steps and pH-dependent substrate inhibition behavior.
AB  - Serine hydroxymethyltransferase (SHMT), an essential enzyme for cell growth and
      development, catalyzes the transfer of -CH2OH from l-serine to tetrahydrofolate
      (THF) to form glycine and 5,10-methylenetetrahydrofolate (MTHF) which is used for
      nucleotide synthesis. Insights into the ligand binding and inhibition properties
      of human cytosolic SHMT (hcSHMT) and Plasmodium SHMT (PvSHMT) are crucial for
      designing specific drugs against malaria and cancer. The results presented here
      revealed strong and pH-dependent THF inhibition of hcSHMT. In contrast, in
      PvSHMT, THF inhibition and the influence of pH were not as pronounced. Ligand
      binding experiments performed at various pH values indicated that the hcSHMT:Gly
      complex binds THF more tightly at lower pH conditions, while the binding affinity
      of the PvSHMT:Gly complex for THF is not pH-dependent. Pre-steady state kinetic
      (rapid-quench) analysis of hcSHMT showed burst kinetics, indicating that glycine
      formation occurs fastest in the first turnover relative to the subsequent
      turnovers i.e. glycine release is the rate-limiting step in the hcSHMT reaction.
      All data suggest that excess THF likely binds E:Gly binary complex and forms the
      E:Gly:THF dead-end complex before glycine is released. A unique flap motif found
      in the structure of hcSHMT may be the key structural feature that imparts these
      described characteristics of hcSHMT.

PMID- 28760599
TI  - Gonadotropin-releasing hormone signaling: An information theoretic approach.
AB  - Gonadotropin-releasing hormone (GnRH) is a peptide hormone that mediates central
      control of reproduction, acting via G-protein coupled receptors that are
      primarily Gq coupled and mediate GnRH effects on the synthesis and secretion of
      luteinizing hormone and follicle-stimulating hormone. A great deal is known about
      the GnRH receptor signaling network but GnRH is secreted in short pulses and much
      less is known about how gonadotropes decode this pulsatile signal. Similarly,
      single cell measures reveal considerable cell-cell heterogeneity in responses to
      GnRH but the impact of this variability on signaling is largely unknown. Ordinary
      differential equation-based mathematical models have been used to explore the
      decoding of pulse dynamics and information theory-derived statistical measures
      are increasingly used to address the influence of cell-cell variability on the
      amount of information transferred by signaling pathways. Here, we describe both
      approaches for GnRH signaling, with emphasis on novel insights gained from the
      information theoretic approach and on the fundamental question of why GnRH is
      secreted in pulses.

PMID- 28760600
TI  - Hypothalamic mitochondrial abnormalities occur downstream of inflammation in diet
      induced obesity.
AB  - Hypothalamic dysfunction is a common feature of experimental obesity. Studies
      have identified at least three mechanisms involved in the development of
      hypothalamic neuronal defects in diet-induced obesity: i, inflammation; ii,
      endoplasmic reticulum stress; and iii, mitochondrial abnormalities. However,
      which of these mechanisms is activated earliest in response to the consumption of
      large portions of dietary fats is currently unknown. Here, we used immunoblot,
      real-time PCR, mitochondrial respiration assays and transmission electron
      microscopy to evaluate markers of inflammation, endoplasmic reticulum stress and
      mitochondrial abnormalities in the hypothalamus of Swiss mice fed a high-fat diet
      for up to seven days. In the present study we show that the expression of the
      inflammatory chemokine fractalkine was the earliest event detected. Its
      hypothalamic expression increased as early as 3 h after the introduction of a
      high-fat diet and was followed by the increase of cytokines. GPR78, an
      endoplasmic reticulum chaperone, was increased 6 h after the introduction of a
      high-fat diet, however the actual triggering of endoplasmic reticulum stress was
      only detected three days later, when IRE-1alpha was increased. Mitofusin-2, a
      protein involved in mitochondrial fusion and tethering of mitochondria to the
      endoplasmic reticulum, underwent a transient reduction 24 h after the
      introduction of a high-fat diet and then increased after seven days. There were
      no changes in hypothalamic mitochondrial respiration during the experimental
      period, however there were reductions in mitochondria/endoplasmic reticulum
      contact sites, beginning three days after the introduction of a high-fat diet.
      The inhibition of TNF-alpha with infliximab resulted in the normalization of
      mitofusin-2 levels 24 h after the introduction of the diet. Thus, inflammation is
      the earliest mechanism activated in the hypothalamus after the introduction of a
      high-fat diet and may play a mechanistic role in the development of mitochondrial
      abnormalities in diet-induced obesity.

PMID- 28760601
TI  - A functional drug re-purposing screening identifies carfilzomib as a drug
      preventing 17beta-estradiol: ERalpha signaling and cell proliferation in breast
      cancer cells.
AB  - Most cases of breast cancer (BC) are estrogen receptor alpha-positive (ERalpha+)
      at diagnosis. The presence of ERalpha drives the therapeutic approach for this
      disease, which often consists of endocrine therapy (ET). 4OH-Tamoxifen and
      faslodex (i.e., fulvestrant - ICI182,780) are two ETs that render tumor cells
      insensitive to 17beta-estradiol (E2)-dependent proliferative stimuli and prevent
      BC progression. However, ET has limitations and serious failures in different
      tissues and organs. Thus, there is an urgent need to identify novel drugs to
      fight BC in the clinic. Re-positioning of old drugs for new clinical purposes is
      an attractive alternative for drug discovery. For this analysis, we focused on
      the modulation of intracellular ERalpha levels in BC cells as target for the
      screening of about 900 Food and Drug Administration (FDA) approved compounds that
      would hinder E2:ERalpha signaling and inhibit BC cell proliferation. We found
      that carfilzomib induces ERalpha degradation and prevents E2 signaling and cell
      proliferation in two ERalpha+ BC cell lines. Remarkably, the analysis of
      carfilzomib effects on a cell model system with an acquired resistance to 4OH
      tamoxifen revealed that this drug has an antiproliferative effect superior to
      faslodex in BC cells. Therefore, our results identify carfilzomib as a drug
      preventing E2:ERalpha signaling and cell proliferation in BC cells and suggest
      its possible re-position for the treatment of ERalpha+ BC as well as for those
      diseases that have acquired resistance to 4OH-tamoxifen.

PMID- 28760602
TI  - Longer wait times affect future use of VHA primary care.
AB  - BACKGROUND: Improving access to the Veterans Health Administration (VHA) is a
      high priority, particularly given statutory mandates of the Veterans Access,
      Choice and Accountability Act. This study examined whether patient-reported wait
      times for VHA appointments were associated with future reliance on VHA primary
      care services. METHODS: This observational study examined 13,595 VHA patients
      dually enrolled in fee-for-service Medicare. Data sources included VHA
      administrative data, Medicare claims and the Survey of Healthcare Experiences of
      Patients (SHEP). Primary care use was defined as the number of face-to-face
      visits from VHA and Medicare in the 12 months following SHEP completion. VHA
      reliance was defined as the number of VHA visits divided by total visits
      (VHA+Medicare). Wait times were derived from SHEP responses measuring the usual
      number of days to a VHA appointment with patients' primary care provider for
      those seeking immediate care. We defined appointment wait times categorically: 0
      days, 1day, 2-3 days, 4-7 days and >7 days. We used fractional logistic
      regression to examine the relationship between wait times and reliance. RESULTS:
      Mean VHA reliance was 88.1% (95% CI = 86.7% to 89.5%) for patients reporting 0day
      waits. Compared with these patients, reliance over the subsequent year was 1.4 (p
      = 0.041), 2.8 (p = 0.001) and 1.6 (p = 0.014) percentage points lower for
      patients waiting 2-3 days, 4-7 days and >7 days, respectively. CONCLUSIONS:
      Patients reporting longer usual wait times for immediate VHA care exhibited lower
      future reliance on VHA primary care. IMPLICATIONS: Longer wait times may reduce
      care continuity and impact cost shifting across two federal health programs.

PMID- 28760603
TI  - Simultaneous determination of intracellular nucleotides and coenzymes in Yarrowia
      lipolytica producing lipid and lycopene by capillary zone electrophoresis.
AB  - Yarrowia lipolytica is an oleaginous yeast with promise in producing terpenoids
      such as lycopene. Though methods for analyzing primary metabolic intermediates
      have been established, further work is needed to better analyze nucleotides and
      coenzymes. Here, we presented an optimized method for the separation of
      nucleotides and coenzymes in Y. lipolytica using the capillary electrophoresis.
      The separation of twelve metabolites including four coenzymes, five nucleotides
      and three nucleosides was achieved within 32min using a voltage of 15kV and 70mM
      sodium carbonate/hydrogencarbonate buffer with 1.0% beta-CD at pH 10. The results
      show that the concentrations of adenosine triphosphate and nicotinamide adenine
      dinucleotide phosphate changed significantly between lycopene producing strain
      and the control, indicating that these two metabolites may be closely related
      with lycopene production. The optimized method provides a useful approach for
      future metabolic analysis of fermentation process as well as industrial strain
      improvement.

PMID- 28760604
TI  - Application of quality by design concept to develop a dual gradient elution
      stability-indicating method for cloxacillin forced degradation studies using
      combined mixture-process variable models.
AB  - Penicillins are typical of complex ionic samples which likely contain large
      number of degradation-related impurities (DRIs) with different polarities and
      charge properties. It is often a challenge to develop selective and robust high
      performance liquid chromatography (HPLC) methods for the efficient separation of
      all DRIs. In this study, an analytical quality by design (AQbD) approach was
      proposed for stability-indicating method development of cloxacillin. The
      structures, retention and UV characteristics rules of penicillins and their
      impurities were summarized and served as useful prior knowledge. Through quality
      risk assessment and screen design, 3 critical process parameters (CPPs) were
      defined, including 2 mixture variables (MVs) and 1 process variable (PV). A
      combined mixture-process variable (MPV) design was conducted to evaluate the 3
      CPPs simultaneously and a response surface methodology (RSM) was used to achieve
      the optimal experiment parameters. A dual gradient elution was performed to
      change buffer pH, mobile-phase type and strength simultaneously. The design
      spaces (DSs) was evaluated using Monte Carlo simulation to give their possibility
      of meeting the specifications of CQAs. A Plackett-Burman design was performed to
      test the robustness around the working points and to decide the normal operating
      ranges (NORs). Finally, validation was performed following International
      Conference on Harmonisation (ICH) guidelines. To our knowledge, this is the first
      study of using MPV design and dual gradient elution to develop HPLC methods and
      improve separations for complex ionic samples.

PMID- 28760605
TI  - Advanced fingerprinting of high-quality cocoa: Challenges in transferring methods
      from thermal to differential-flow modulated comprehensive two dimensional gas
      chromatography.
AB  - The possibility to transfer methods from thermal to differential-flow modulated
      comprehensive two-dimensional gas chromatographic (GC*GC) platforms opens
      interesting perspectives for routine analysis of complex samples. Flow modulated
      platforms avoid the use of cryogenics, thereby simplifying laboratory operations
      and analyst supervision during intensive analytical sessions. This study
      evaluates the feasibility of transferring a fingerprinting method capable of
      classifying and discriminating cocoa samples based on the volatiles fraction
      composition according to their origin and processing steps. Previously developed
      principles of GC*GC method translation are applied to an original fingerprinting
      method, developed for a loop-type thermal modulated GC*GC-MS system, to engineer
      a method for a reverse-injection differential flow modulated platform (GC*2GC
      MS/FID) with a dual-parallel secondary column and dual detection. Effective
      method translation preserves analytes elution order, 1D resolution, and 2D
      pattern coherence. The experimental results confirm the feasibility of
      translating fingerprinting method conditions while preserving the informative
      power of 2D peak patterns for sample classification and discrimination. Correct
      translation enables effective transfer of metadata (e.g., compound names and MS
      fragmentation patterns) by automatic template transformation and matching from
      the original/reference method to its translated counterpart. Although the
      adoption of a narrow bore (i.e. 0.1mm dc) column in the first-dimension enabled
      operation under close-to-optimal conditions with the differential-flow modulation
      platform, due to the dual-parallel columns in the second-dimension, it resulted
      in lower overall method sensitivity. Nevertheless, fingerprinting accuracy was
      preserved and most of the key-aroma compounds and technological markers were
      effectively mapped, thus limiting the loss of fingerprinting information.

PMID- 28760606
TI  - Synthesis, analytical characterization and capillary electrophoretic use of the
      single-isomer heptakis-(6-O-sulfobutyl)-beta-cyclodextrin.
AB  - This contribution reports the synthesis, characterization and capillary
      electrophoretic application of heptakis-(6-O-sulfobutyl-ether)-beta-cyclodextrin
      sodium salt, (6-(SB)7-beta-CD). The compound was obtained through a five-steps
      synthesis and it represents the first example of single-isomer sulfobutylated
      cyclodextrin that carries the negatively charged functions exclusively on its
      primary side and it is unmodified on the lower rim. The purity of each
      intermediate was determined by appropriate liquid chromatographic methods, while
      the isomeric purity of the final product was established by an ad-hoc developed
      HPLC method based on a CD-Screen-IEC column. The structural identification of 6
      (SB)7-beta-CD was carried out by 1D, 2D NMR spectroscopy and ESI-MS. The chiral
      separation ability of 6-(SB)7-beta-CD was studied by chiral capillary
      electrophoresis using the single-isomer host as a background electrolyte additive
      to separate the enantiomers of a representative set of pharmacologically
      significant model compounds such as verapamil, dapoxetine, ondansetron,
      propranolol, atenolol, metoprolol, carvedilol, terbutaline, amlodipine and
      tadalafil. The enantiomer migration order and the effects of the selector
      concentration on the enantiorecognition properties were investigated. NMR
      spectroscopy was applied to deepen and further confirm the host-guest
      interactions and in the case of the model compound dapoxetine a potential
      representation for the supramolecular assembly was developed based on the dataset
      collected by the extensive 2D NMR analysis. This single-isomer chiral selector
      offers a new alternative to the widely applied randomly sulfobutylated- and
      sulfated-beta-cylodextrins as well as to the single-isomer sulfated and
      carboxymethylated derivatives in chiral separations.

PMID- 28760607
TI  - Phenolic glycosides and monoterpenoids from the roots of Euphorbia ebracteolata
      and their bioactivities.
AB  - The bioactive substance investigation of Euphorbia ebracteolata obtained 17
      compounds by various chromatographic techniques. Their structures were elucidated
      using widely spectroscopic data, including ESI-MS, HRESI-MS, CD, 1D- and 2D-NMR,
      which gave 5 new phenolic glucosides and 4 new monoterpenoids. The phenolic
      glucosides and monoterpenoids showed the inhibitory effect against the human
      carboxylesterase-2 (hCE-2) using a fluorescence bioassay in vitro, with the
      strongest inhibitor compound 4 (IC50 7.17MUM). The antioxidant effects of these
      isolated compounds were evaluated using a DPPH scavenging assay. All of the
      phenolic acids displayed the DPPH scavenging effect, especially that eight
      compounds have better effect than vitamin C, with the IC50 values ranging from
      4.52 to 7.52MUM. Additionally, compounds 1-17 showed no cytotoxic effect against
      five human cancer cell lines by MTT assay.

PMID- 28760608
TI  - Effects of an over-ground exoskeleton on external knee moments during stance
      phase of gait in healthy adults.
AB  - BACKGROUND: Physical activity and exercise is central to conservative management
      of knee osteoarthritis (KOA), but is often difficult for patients with KOA to
      maintain over the decade or more prior to surgical management. Better approaches
      are needed for maintaining physical function and health in this population that
      can also address the patho-biomechanics of the osteoarthritic knee. The objective
      of the study is to quantify how a lower-extremity robotic exoskeleton
      (dermoskeleton) modifies the external knee moments during over-ground walking in
      a sample of healthy adults, and to evaluate these biomechanical modifications in
      the context of the osteoarthritic knee. METHOD: Motion analysis data was acquired
      for 13 participants walking with and without the dermoskeleton. Force plate data,
      external knee moment arms, and knee moments in the laboratory and tibia frames of
      reference were computed, as well as time-distance parameters of walking, and
      compared between the two conditions. RESULTS: Although gait speed was not
      different, users took shorter and wider steps when walking with the
      dermoskeleton. Ground reaction forces and early-stance knee moment increased due
      to the added mass of the dermoskeleton, but the knee adduction moment was
      significantly reduced in late stance phase of gait. There was no effect on the
      knee torsional moment when measured in the anatomical frame of reference, and the
      late-stance knee flexion moment was invariant. CONCLUSIONS: The dermoskeleton
      demonstrated favorable biomechanical modifications at the knee in healthy adults
      while walking. Studies are warranted to explore this technology for enabling
      physical activity-based interventions in patients with KOA.

PMID- 28760609
TI  - Influenza vaccination rates in children decline when the live attenuated
      influenza vaccine is not recommended.
AB  - BACKGROUND: In 2016 the Centers for Disease Control and Prevention (CDC)
      recommended against using the live attenuated influenza vaccine (LAIV) for the
      2016-2017 influenza season. This recommendation is potentially important for
      vaccination rates because perceived effectiveness and ease of administration are
      among the primary determinants of families decisions to vaccinate their children.
      This investigation sought to determine whether rates of pediatric influenza
      vaccination changed in a season when the LAIV was not recommended. METHODS: This
      study used cohort and cross sectional data from an academic primary care
      pediatric center in central Pennsylvania that serves approximately 12,500
      patients. Early season (prior to November 1) and end-of-season (prior to March 1)
      vaccination rates in the 2015-16 and 2016-17 influenza seasons were recorded for
      individuals 2-17years old. Repeat vaccination rates (percentage of children
      receiving influenza vaccination in one season who were also vaccinated in the
      next season) were recorded for the 2015-16 into 2016-17 seasons. A logistic
      regression model adjusting for race, ethnicity, age, insurance type and type of
      vaccination received was employed to identify predictors of repeat vaccination.
      RESULTS: In the absence of LAIV (2016-17) early vaccination rates were
      significantly higher (24.7% vs 22.8%, p=0.004), but end-of-season rates were
      lower (50.4% vs 52.0%, p=0.03) than when LAIV was offered (2015-16). After
      adjusting for covariates, those who had received IIV in the 2015-16 season had
      higher odds (OR 1.32, 95% CI, 1.15-1.52) of getting a repeat vaccination in the
      2016-17 season, compared with those who had received LAIV in the 2015-16 season.
      CONCLUSIONS: End-of-season vaccination rates were lower in 2016-17 when LAIV was
      not recommended, particularly among children who received LAIV in the preceding
      year. Unavailability of LAIV in the 2016-17 season may have impacted influenza
      vaccination convenience and perceived effectiveness, two factors which could
      influence vaccine uptake in pediatric populations.

PMID- 28760610
TI  - Macrophage-derived insulin-like growth factor-1 affects influenza vaccine
      efficacy through the regulation of immune cell homeostasis.
AB  - The level of antibody production induced by a vaccine involves a variety of host
      factors. One of these, insulin-like growth factor-1 (IGF-1), plays an important
      role in lymphocyte maturation and antibody expression. Here, we investigated the
      role of macrophage-derived IGF-1 in the induction of influenza vaccine-specific
      antibodies using macrophage-derived IGF-1 gene knockout (MIKO) mice. The titers
      of vaccine-specific total immunoglobulin G (IgG) and IgG1 after immunization were
      about two- to fourfold lower in MIKO mice than in WT mice. Moreover, MIKO mice
      showed a relatively weak booster effect of repeated immunization. In contrast,
      antigen-nonspecific total IgG was about threefold higher in MIKO mice than in WT
      mice. After viral challenge, the viral titer and the pathological damage in lungs
      of MIKO mice were higher than those in WT mice despite vaccination.
      Interestingly, the proportions of proinflammatory immune cells including M1
      macrophages, Th1 and Th17 cells was higher in unvaccinated MIKO mice than in
      unvaccinated WT mice. This suggests that nonspecific activation of immune cells
      may paradoxically impair the response to the vaccine. In addition, although the
      proportions of T follicular helper (Tfh) cells and GL-7+ germinal center (GC) B
      cells were higher in MIKO mice than in WT mice, the population of CD138+B220+
      antibody-secreting plasmablasts was lower in MIKO mice, which may be a cause of
      the low influenza-specific antibody titer in MIKO mice. Taken together, these
      results suggest that macrophage-derived IGF-1 might play an important role in the
      vaccine-triggered immune response by regulating immune cell homeostasis.

PMID- 28760612
TI  - Measles vaccines: WHO position paper, April 2017 - Recommendations.
AB  - This article presents the World Health Organization's (WHO) recommendations on
      the use of measles vaccines excerpted from the WHO position paper on Measles
      vaccines: WHO position paper - April 2017, published in the Weekly
      Epidemiological Record [1]. This position paper replaces the 2009 WHO position
      paper on measles vaccines [2]. The position paper summarizes the most recent
      developments in the field of measles and includes removal of introduction
      criteria for the routine second dose of measles-containing vaccine (MCV2),
      guidance on when to vaccinate infants from 6months of age, and guidance on re
      vaccination of HIV-infected children receiving highly active anti-retroviral
      therapy (HAART). Footnotes to this paper provide a number of core references
      including references to grading tables that assess the quality of the scientific
      evidence, and to the evidence-to-recommendation table. In accordance with its
      mandate to provide guidance to Member States on health policy matters, WHO issues
      a series of regularly updated position papers on vaccines and combinations of
      vaccines against diseases that have an international public health impact. These
      papers are concerned primarily with the use of vaccines in large-scale
      immunization programmes; they summarize essential background information on
      diseases and vaccines, and conclude with WHO's current position on the use of
      vaccines in the global context. Recommendations on the use of measles vaccines
      were discussed by SAGE in November 2013, October 2015 and October 2016; evidence
      presented at these meetings can be accessed at:
      www.who.int/immunization/sage/meetings/2013/november/presentations_background_doc
      /en/,
      www.who.int/immunization/sage/meetings/2015/october/presentations_background_docs
      en/ and
      www.who.int/immunization/sage/meetings/2016/october/presentations_background_docs
      en/.

PMID- 28760611
TI  - Chronically ill adolescents are also incompletely vaccinated: A cross-sectional
      study in France.
AB  - BACKGROUND: Adolescent vaccination coverage tends to be suboptimal, leading to
      resurgent infectious pathologies and vulnerability to various pathogens. The low
      frequency of medical consultations and missed opportunities for vaccination are
      often used to explain the low rate of vaccination. The aim of this study was to
      assess if the vaccination coverage rate is higher in chronically ill adolescents
      (CIA) who require a close pediatric specialized follow-up versus the rate in
      healthy adolescents (HA). METHODS: A monocentric cross-sectional study was
      conducted in the Nantes University Hospital. We included 114 CIA and 266 HA. The
      vaccination coverage rate and the up-to-date immunization status were compared
      between ill versus healthy adolescents for each of the following vaccines:
      diphtheria, tetanus, acellular pertussis, inactivated poliovirus (DTaP/IPV),
      measles-mumps-rubella (MMR), hepatitis B (HepB), meningococcal C conjugate (MnC),
      human papillomavirus (HPV) and composite combinations (e.g. DTaP/IPV-MMR-HepB
      MnC). RESULTS: The overall immunization rate for DTaP/IPV-MMR-HepB-MnC was very
      low, with no significant difference between CIA and HA (9.6% versus 13.5%;
      p=0.28). Most of the investigated vaccines exhibited similar immunization
      patterns for the two groups: DTaP/IPV (77.2vs. 76.7%; p=0.97), MMR (92.1vs.
      95.9%; p=0.14), HepB (51.8vs. 48.5%; p=0.51) with the exception of the MnC
      (18.4vs. 27.8%; p=0.05) and HPV (28.6vs. 16.1%; p=0.04). CONCLUSION: Despite
      undergoing specialized and close medical follow-up, we found that the vaccination
      coverage rate for the CIA remained suboptimal. This indicates that pediatricians
      need to check the vaccination status and, when required, ensure that the
      vaccination schedules for these fragile patients are up-to-date.

PMID- 28760613
TI  - WHO position paper, Meningococcal A conjugate vaccine: Updated guidance, February
      2015.
AB  - This article presents the World Health Organization's (WHO) updated
      recommendations on the use of meningococcal vaccines excerpted from the WHO
      position paper on Meningococcal A conjugate vaccine: updated guidance, February
      2015, published in the Weekly Epidemiological Record [1]. A position paper on
      meningococcal vaccines was published in 2011 and its recommendations remain valid
      [2]. This update adds to the previous recommendations specifically concerning
      routine immunization of infants and young children in the African meningitis belt
      with meningococcal A conjugate vaccine. Footnotes to this paper provide a number
      of core references including references to grading tables that assess the quality
      of the scientific evidence. In accordance with its mandate to provide guidance to
      Member States on health policy matters, WHO issues a series of regularly updated
      position papers on vaccines and combinations of vaccines against diseases that
      have an international public health impact. These papers are concerned primarily
      with the use of vaccines in large-scale immunization programmes; they summarize
      essential background information on diseases and vaccines, and conclude with
      WHO's current position on the use of vaccines in the global context.
      Recommendations on the use of the Meningococcal A conjugate vaccine were
      discussed by SAGE in October 2014; evidence presented at these meetings can be
      accessed at:
      http://www.who.int/immunization/sage/meetings/2014/october/presentations_backgrou
      d_docs/en/.

PMID- 28760614
TI  - Regulatory considerations in development of vaccines to prevent disease caused by
      Chikungunya virus.
AB  - Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus. Chikungunya
      disease (CHIK) in humans is characterized by sudden onset of high fever,
      cutaneous rash, myalgia and debilitating polyarthralgia. Until recently the virus
      was considered endemic to only Africa and Asia, but since 2004 CHIK has spread to
      previously non-endemic regions, including Europe and the Americas, thereby
      emerging as a global health threat. Although a variety of CHIKV vaccine
      candidates have been tested in animals, and a few have advanced to human clinical
      trials, no licensed vaccine is currently available for prevention of disease. In
      this article, we review recent efforts in CHIKV vaccine development and discuss
      regulatory considerations for CHIKV vaccine licensure under U.S. FDA regulations.
      Several licensure pathways are available, and the most appropriate licensure
      pathway for a CHIK vaccine will depend on the type of evidence that can be
      generated to demonstrate the vaccine's effectiveness. If "traditional approval"
      following demonstration of direct benefit in adequate and well-controlled
      clinical disease endpoint studies is not possible, the Accelerated Approval and
      Animal Rule pathways are potential alternatives. In terms of vaccine safety, the
      potential for vaccine associated arthralgia and antibody-dependent enhancement of
      infectivity and disease severity are important issues that should be addressed in
      both pre-clinical and clinical studies. CHIK vaccine developers are encouraged to
      communicate with the FDA during all stages of vaccine development.

PMID- 28760615
TI  - Benevolent personification of the MoH increases compliance with an emergency
      polio vaccination.
AB  - OBJECTIVE: Parental compliance is crucial to the success of mass vaccination
      campaigns targeting children. Relying on psychological/neuroscientific research
      concerning the role of personification (i.e., viewing the inanimate as human) in
      behavior, the authors examined the effect of parents' personification of the
      Israeli Ministry of Health (MoH) on compliance with a publicly controversial mass
      vaccination campaign, which was aimed at stopping the spread of a wild
      poliovirus. METHODS: Participants were 555 parents of children aged 9 or younger,
      residing in the center/north of Israel, an area covered by Phase 2 of the
      campaign. T1 assessment, employed two days prior to Phase 2, tapped into
      demographics, attitudes towards vaccination, intent to comply, and a benevolent
      personification of the MoH (i.e., "The MoH is caring") vs. a malevolent
      personification of the MoH ("The MoH is hysteric"). T2 assessment, transpiring
      four months after the end of the campaign, addressed presence and reasons for
      (non-)compliance. RESULTS: The study's overall compliance rate was 61.8%. The
      principal reason for compliance was "adherence to the recommendations of the MoH"
      (68.49%). In a multivariate logistic regression analysis, prospective predictors
      of compliance were: an early intent to comply (O.R.=2.56, p=0.000), being male
      (O. R.=1.51, p=0.023), and a benevolent personification of the MoH (O.R.=1.21,
      p=0.019). CONCLUSION: Parents who experienced the Israeli MoH as a benevolent
      protagonist were more likely to comply with the mass vaccination campaign.
      Findings highlight the role of leadership in public health campaigns during
      emergencies.

PMID- 28760616
TI  - The benefit of the doubt or doubts over benefits? A systematic literature review
      of perceived risks of vaccines in European populations.
AB  - OBJECTIVES: The success of vaccination strategies depends in part on population
      perceptions of benefits and risks of vaccines and related confidence in
      vaccination. Better knowledge of public concerns about vaccines and what is
      driving them is needed to inform vaccination strategies and communications. This
      literature reviewer examined studies on vaccine and vaccination risk perceptions
      and concerns across European populations. METHODS: A systematic literature review
      was conducted to identify studies published between 2004 and 2014 in Europe. A
      descriptive analysis was performed. FINDINGS: A total of 145 articles were
      selected, most of which were conducted in the UK, the Netherlands and France and
      studied seasonal influenza, HPV and pandemic influenza vaccination. Across all
      countries and vaccines, the primary area of concern was vaccine safety, followed
      by perceptions of low likelihood of contracting vaccine-preventable diseases
      (VPDs), perceived low severity of VPDs, beliefs that vaccines do not work, and
      overall lack of information. Concerns were found to be vaccine-, country- and
      population-specific. CONCLUSION: In addition to identifying concerns about
      vaccination in Europe, this study confirmed the notion that individuals have many
      safety concerns about vaccination and often believe that the risks of vaccination
      outweigh their benefits. More research needs to be conducted to explore the
      impact of different types of communication strategies, which would frame the
      benefits of vaccination as well as risks of not vaccinating. Strategies to better
      inform public perceptions of vaccines should include the provision of unbiased,
      comprehensive information tailored to population information needs, and delivered
      using multiple and new communication technologies such as social media.

PMID- 28760617
TI  - Well-differentiated, pedunculated liposarcoma of the hypopharynx.
AB  - INTRODUCTION: Liposarcoma of the hypopharynx is extremely rare, as only 28 cases
      have been reported in the literature. The cardinal symptom of liposarcoma is
      progressively worsening dysphagia. CASE REPORT: The authors report the case of a
      71-year-old man who presented with dysphagia, marked weight loss over several
      weeks and an episode of exteriorization of a solid mass from the mouth during an
      episode of vomiting. Imaging revealed a fat density intra-oesophageal mass.
      Panendoscopy and upper gastrointestinal endoscopy visualized the pedunculated
      tumour in the left piriform sinus, which was able to be exteriorized via the
      mouth. The tumour was then resected endoscopically at its hypopharyngeal
      insertion pedicle. Histological examination of the operative specimen concluded
      on well-differentiated benign liposarcoma. DISCUSSION: Well-differentiated
      liposarcoma is the most common form of liposarcoma, but is only exceptionally
      reported in the hypopharynx. The main symptoms are related to compression of
      adjacent structures. Imaging findings are nonspecific. Only histological
      examination can distinguish liposarcoma from other benign oesophageal tumours.
      Standard treatment consists of wide, complete resection, which is not always
      possible in the neck. Long-term follow-up of these patients is essential in order
      to rapidly detect recurrence.

PMID- 28760618
TI  - Control of vertigo in Meniere's disease by intratympanic dexamethasone.
AB  - OBJECTIVE: The main objective was to assess the efficacy of intratympanic
      dexamethasone injection in controlling vertigo in unilateral Meniere's disease
      refractory to medical treatment. MATERIALS AND METHODS: A retrospective study
      included 25 patients with disabling unilateral Meniere's disease, defined
      according to the American Academy of Otorhinolaryngology-Head and Neck Surgery
      (AAO-HNS) criteria. Patients received intratympanic dexamethasone during the
      monitoring period. Control of vertigo was classified according to AAO-HNS vertigo
      control index, at 6 months, 1 year, and 2 years after treatment initiation.
      Complications and progression of hearing were also assessed. RESULTS:
      Satisfactory control (class A or B) was obtained in 92% of patients (n=23/25) at
      6 months, 68% (n=17/25) at 1 year, and 70% (n=16/23) at 2 years. There was no
      worsening of hearing in those patients who were well-controlled by this
      therapeutic strategy. No local or systemic complications were observed during
      follow-up. CONCLUSION: Dexamethasone is part of the management strategy for
      patients with Meniere's disease refractory to conventional treatment, implemented
      before destructive treatment. It achieves control of vertigo in 70% of patients
      at 2 years.

PMID- 28760620
TI  - Microcontact printing of polydopamine on thermally expandable hydrogels for
      controlled cell adhesion and delivery of geometrically defined microtissues.
AB  - : Scaffold-free harvest of microtissue with a defined structure has received a
      great deal of interest in cell-based assay and regenerative medicine. In this
      study, we developed thermally expandable hydrogels with spatially controlled cell
      adhesive patterns for rapid harvest of geometrically controlled microtissue. We
      patterned polydopamine (PD) on to the hydrogel via microcontact printing (MUCP),
      in linear shapes with widths of 50, 100 and 200MUm. The hydrogels facilitated
      formation of spatially controlled strip-like microtissue of human dermal
      fibroblasts (HDFBs). It was possible to harvest and translocate microtissues with
      controlled widths of 61.4+/-14.7, 104.3+/-15.6, and 186.6+/-22.3MUm from the
      hydrogel to glass substrates by conformal contact upon expansion of the hydrogel
      in response to a temperature change from 37 to 4 degrees C, preserving high
      viability, extracellular matrix, and junction proteins. Microtissues were readily
      translocated in vivo to the subcutaneous tissue of mouse. The microtissues were
      further utilized as a simple assay model for monitoring of contraction in
      response to ROCK1 inhibitor. Collectively, micro-sized patterning of PD on the
      thermally expandable hydrogels via MUCP holds promise for the development of
      microtissue harvesting systems that can be employed to ex vivo tissue assay and
      cell-based therapy. STATEMENT OF SIGNIFICANCE: Harvest of artificial tissue with
      controlled cellular arrangement independently from external materials has been
      widely studied in cell-based assay and regenerative medicine. In this study, we
      developed scaffold-free harvest system of microtissues with anisotropic
      arrangement and controlled width by exploiting thermally expandable hydrogels
      with cell-adhesive patterns of polydopamine formed by simple microcontact
      printing. Cultured strips of human dermal fibroblasts on the hydrogels were
      rapidly delivered to various targets ranging from flat coverglass to mice
      subcutaneous tissue by thermal expansion of the hydrogel at 4 degrees C for
      10min. These were further utilized as a drug screening model responding to ROCK1
      inhibitor, which imply its versatile applicability.

PMID- 28760619
TI  - Gamma-irradiated human amniotic membrane decellularised with sodium dodecyl
      sulfate is a more efficient substrate for the ex vivo expansion of limbal stem
      cells.
AB  - : The gold standard substrate for the ex vivo expansion of human limbal stem
      cells (LSCs) remains the human amniotic membrane (HAM) but this is not a defined
      substrate and is subject to biological variability and the potential to transmit
      disease. To better define HAM and mitigate the risk of disease transmission, we
      sought to determine if decellularisation and/or gamma-irradiation have an adverse
      effect on culture growth and LSC phenotype. Ex vivo limbal explant cultures were
      set up on fresh HAM, HAM decellularised with 0.5M NaOH, and 0.5% (w/v) sodium
      dodecyl sulfate (SDS) with or without gamma-irradiation. Explant growth rate was
      measured and LSC phenotype was characterised by histology, immunostaining and qRT
      PCR (ABCG2, DeltaNp63, Ki67, CK12, and CK13). Y-irradiation marginally stiffened
      HAM, as measured by Brillouin spectromicroscopy. HAM stiffness and gamma
      irradiation did not significantly affect the LSC phenotype, however LSCs expanded
      significantly faster on Y-irradiated SDS decellularised HAM (p<0.05) which was
      also corroborated by the highest expression of Ki67 and putative LSC marker,
      ABCG2. Colony forming efficiency assays showed a greater yield and proportion of
      holoclones in cells cultured on Y-irradiated SDS decellularised HAM. Together our
      data indicate that SDS decellularised HAM may be a more efficacious substrate for
      the expansion of LSCs and the use of a gamma-irradiated HAM allows the user to
      start the manufacturing process with a sterile substrate, potentially making it
      safer. STATEMENT OF SIGNIFICANCE: Despite its disadvantages, including its
      biological variability and its ability to transfer disease, human amniotic
      membrane (HAM) remains the gold standard substrate for limbal stem cell (LSC)
      culture. To address these disadvantages, we used a decellularised HAM sterilised
      by gamma-irradiation for LSC culture. We cultured LSCs on fresh HAM, HAM
      decellularised with NaOH, HAM decellularised with sodium dodecyl sulfate (SDS)
      and HAM decellularised with SDS and sterilised with gamma-irradiation. We
      demonstrated that although HAM decellularised with SDS and sterilised with gamma
      irradiation is significantly stiffer this does not affect LSC culture growth rate
      or the phenotype of cultured LSCs. We therefore recommend the use of SDS
      decellularised gamma-irradiated HAM in future LSC clinical trials.

PMID- 28760621
TI  - Distribution of aerobic anoxygenic phototrophs in the Eastern Adriatic Sea.
AB  - The spatial patterns of aerobic anoxygenic phototrophs abundances were
      investigated, for the first time, in the Adriatic Sea. Also, the spatial patterns
      of the whole picoplankton community as well as the environmental factors that
      potentially influence these patterns were highlighted. AAP abundances was in
      average 66.9 +/- 66.8 * 103 cell mL-1, and their proportion in total bacteria was
      7.3 +/- 4.3%. These values are in the upper range of AAP abundances observed in
      marine environments. Multivariate analyses proved that environmental factors
      influenced the picoplankton community interdependently. Chl a was the main
      driving factor for the picoplankton community, accounting for 33.3% of
      picoplankton community variance, followed by NO2- (17.9% of variance explained)
      and temperature (14.2% of variance explained). Chl a showed stronger correlation
      with AAPs, non-pigmented bacteria and Picoeucaryotes than with cyanobacteria.
      Abundance of cyanobacteria was stronger correlated to salinity and the N:P ratio
      than to nutrient concentrations.

PMID- 28760622
TI  - Consumption of particulate wastes derived from cage fish farming by aggregated
      wild fish. An experimental approach.
AB  - Particulate wastes derived from cage fish farming are a trophic resource used by
      wild fish. This study assesses waste consumption by wild fish and the impact on
      the final balance of wastes. Consumption was determined according to the
      difference between the particulate matter exiting the cages and that reaching 5 m
      away at three different depths, in the presence and absence of wild fish. Wild
      fish around the experimental cages were counted during feeding and non-feeding
      periods. A weighted abundance of 1057 fish 1000 m-3 consumed 17.75% of the
      particulate wastes exiting the cages, on average. Consumption was higher below
      the cages, where waste outflow was greater. However, waste removal by wild fish
      was noteworthy along the shallow and deep sides of the cages. Wild fish
      diminished the net particulate wastes by about 14%, transforming them into more
      easily dispersible and less harmful wastes. This study demonstrates the
      mitigating potential of wild fish in reducing environmental impact.

PMID- 28760623
TI  - Pregnane X receptor (PXR) signaling in seabream primary hepatocytes exposed to
      extracts of seawater samples collected from polycyclic aromatic hydrocarbons
      (PAHs)-contaminated coastal areas.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants
      damaging to the marine environment and the wildlife. Herein, we investigated the
      effects of extracts from coastal seawaters (central Adriatic sea, Italy), showing
      high concentrations of PAHs, on pregnane X receptor (PXR)-transcriptional
      regulation of the cytochrome P450 3A (CYP3A) gene using seabream primary
      hepatocytes. The results show that concentrated extracts of seawater with
      original SigmaPAH concentrations above the putative threshold of 30 ng L-1
      increased expression of PXR and its main target gene, CYP3A. Similar results were
      observed for LXR and its target gene SREBP-1c suggesting pathway cross-talk.
      These data are further supported by the finding of multiple PXR and LXR response
      elements in the putative promoters of their target genes. Overall, our data
      indicate the capacity of seawater extracts, containing environmentally relevant
      levels of PAHs, to affect multiple pathways, including lipid and cholesterol
      metabolism.

PMID- 28760624
TI  - Effect of ocean acidification on growth, calcification, and gene expression in
      the pearl oyster, Pinctada fucata.
AB  - In this study, shell growth, shell microstructure, and expression levels of shell
      matrix protein genes (aspein, n16, and nacrein) that play a key role in the CaCO3
      crystal polymorphism (calcite and aragonite) of the shell were investigated in
      the pearl oyster Pinctada fucata at pH 8.10, 7.70, and 7.40. We found that the
      shell length and total weight index did not vary significantly between oysters
      reared at pH 8.10 and 7.70, but was significantly lower at pH 7.40. Calcium
      content and shell hardness were not significantly different between pH 8.10 and
      7.70, but were significantly different at pH 7.40. At pH 7.40, the shell
      exhibited a poorly organized nacreous microstructure, and showed an apparent loss
      of structural integrity in the nacreous layer. The prismatic layer appeared
      morphologically dissimilar from the samples at pH 8.10 and 7.70. The internal
      layer was corroded and had dissolved. At pH 7.40, the expression levels of
      nacrein, aspein, and n16 decreased on day 1, and remained low between days 2 and
      42. The expression levels of these genes were significantly lower at pH 7.40 than
      at pH 8.10 and 7.70 during days 2-42. These results suggest that ocean
      acidification will have a limited impact on shell growth, calcification, and
      associated gene expression levels at a pH of 7.70, which is projected to be
      reached by the end of the century. The negative effects were found on
      calcification and gene expression occurred at the lowest experimental pH (7.40).

PMID- 28760625
TI  - Methylglyoxal upregulates Dictyostelium discoideum slug migration by triggering
      glutathione reductase and methylglyoxal reductase activity.
AB  - Glutathione (GSH)-deprived Dictyostelium discoideum accumulates methylglyoxal
      (MG) and reactive oxygen species (ROS) during vegetative growth. However, the
      reciprocal effects of the production and regulation of these metabolites on
      differentiation and cell motility are unclear. Based on the inhibitory effects of
      gamma-glutamylcysteine synthetase (gcsA) disruption and GSH reductase (gsr)
      overexpression on aggregation and culmination, respectively, we overexpressed GSH
      related genes encoding superoxide dismutase (Sod2), catalase (CatA), and Gcs, in
      D. discoideum. Wild-type KAx3 and gcsA-overexpressing (gcsAOE) slugs maintained
      GSH levels at levels of approximately 2.1-fold less than the reference GSH
      synthetase-overexpressing mutant; their GSH levels did not correlate with slug
      migration ability. Through prolonged KAx3 migration by treatment with MG and
      H2O2, we found that MG increased after the mound stage in this strain, with a 2.6
      fold increase compared to early developmental stages; in contrast, ROS were
      maintained at high levels throughout development. While the migration-defective
      sod2- and catA-overexpressing mutant slugs (sod2OE and catAOE) decreased ROS
      levels by 50% and 53%, respectively, these slugs showed moderately decreased MG
      levels (36.2+/-5.8 and 40.7+/-1.6nmolg-1 cells wet weight, P<0.05) compared to
      the parental strain (54.2+/-3.5nmolg-1). Importantly, defects in the migration of
      gcsAOE slugs decreased MG considerably (13.8+/-4.2nmolg-1, P<0.01) along with a
      slight decrease in ROS. In contrast to the increase observed in migrating sod2OE
      and catAOE slugs by treatment with MG and H2O2, the migration of gcsAOE slugs
      appeared unaffected. This behavior was caused by MG-triggered Gsr and NADPH
      linked aldolase reductase activity, suggesting that GSH biosynthesis in gcsAOE
      slugs is specifically used for MG-scavenging activity. This is the first report
      showing that MG upregulates slug migration via MG-scavenging-mediated
      differentiation.

PMID- 28760626
TI  - How do the brain's time and space mediate consciousness and its different
      dimensions? Temporo-spatial theory of consciousness (TTC).
AB  - Time and space are the basic building blocks of nature. As a unique existent in
      nature, our brain exists in time and takes up space. The brain's activity itself
      also constitutes and spreads in its own (intrinsic) time and space that is
      crucial for consciousness. Consciousness is a complex phenomenon including
      different dimensions: level/state, content/form, phenomenal aspects, and
      cognitive features. We propose a Temporo-spatial Theory of Consciousness (TTC)
      focusing primarily on the temporal and spatial features of the brain activity. We
      postulate four different neuronal mechanisms accounting for the different
      dimensions of consciousness: (i) "temporo-spatial nestedness" of the spontaneous
      activity accounts for the level/state of consciousness as neural predisposition
      of consciousness (NPC); (ii) "temporo-spatial alignment" of the pre-stimulus
      activity accounts for the content/form of consciousness as neural prerequisite of
      consciousness (preNCC); (iii) "temporo-spatial expansion" of early stimulus
      induced activity accounts for phenomenal consciousness as neural correlates of
      consciousness (NCC); (iv) "temporo-spatial globalization" of late stimulus
      induced activity accounts for the cognitive features of consciousness as neural
      consequence of consciousness (NCCcon).

PMID- 28760627
TI  - Egocentric and allocentric spatial reference frames in aging: A systematic
      review.
AB  - Aging affects many aspects of everyday living, such as autonomy, security and
      quality of life. Among all, spatial memory and spatial navigation show a gradual
      but noticeable decline, as a result of both neurobiological changes and the
      general slowing down of cognitive functioning. We conducted a systematic review
      using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis
      (PRISMA) guidelines to identify studies that specifically investigated the role
      of allocentric and egocentric frames in healthy aging. Concerning spatial
      navigation, our results showed a preservation of egocentric strategies, along
      with specific impairments in the use of allocentric and switching abilities.
      Regarding spatial memory, instead, outcomes were more divergent and not frame
      specific. With this perspective, spatial impairments were discussed considering
      the cognitive profile of mild cognitive impairment (MCI) and Alzheimer's Disease
      (AD).

PMID- 28760628
TI  - Laparoscopic Minimally Invasive Approach to Sentinel Lymph Node Mapping of the
      Ovary Using the Near-infrared Fluorescent S1 HD Pinpoint System with Indocyanine
      Green Dye.
AB  - STUDY OBJECTIVE: To show a novel minimally invasive approach to sentinel lymph
      node (SLN) detection of the ovary with near-infrared-guided surgery using
      indocyanine green (ICG). DESIGN: A step by step description of the technique with
      video and figures (educational video). SETTING: The standard surgical staging of
      early-stage I-II ovarian cancer includes systematic pelvic and aortic
      lymphadenectomy even in the absence of clear evidence regarding the survival
      benefits associated with comprehensive retroperitoneal staging. The ideal
      candidates are all women undergoing a surgical approach with frozen section
      analysis for highly suspicious ovarian masses or patients in whom an adnexal mass
      has been removed that appeared to be malignant and an open or laparoscopic
      surgical staging procedure is planned. PATIENT: A 31-year-old woman with occult
      ovarian cancer after simple left ovarian cystectomy. INTERVENTIONS: Laparoscopic
      surgical staging including simple hysterectomy, bilateral salpingo-oophorectomy,
      omentectomy, pelvic and aortic bilateral lymphadenectomy, and sentinel node
      biopsy from the left ovary. MEASUREMENTS AND MAIN RESULTS: The surgical
      intervention was performed with the PinPoint 0 degree HD S1 SPY fluorescence
      camera (PinPoint Endoscopic Fluorescence Imaging System; NOVADAQ, Mississauga,
      ON, Canada). After the induction of the pneumoperitoneum, ICG was injected with 2
      separate injections in the proper ovarian ligament and the infundibulopelvic
      ligament, just below the peritoneum, at a concentration of 1.25 mg/mL. A total
      amount of 0.4 mL ICG solution was injected using a percutaneous abdominal
      approach with a 12-cm-long 22-G spinal needle. SLN mapping should be preceded by
      the exposure of the aortic region with a gentle dissection on both sides along
      the Toldt fascia up to the left renal vein. Two SLNs were identified in the left
      inframesenteric para-aortic and superficial left common areas. Both SLNs were
      negative. CONCLUSION: The minimally invasive approach in combination with the ICG
      near-infrared fluorescence S1 PinPoint fluorescence system seems feasible, and,
      in our opinion, even if preliminary, this approach can further extend the range
      of indications of SLN mapping. In the future, this combined approach can
      prospectively involve ovarian SLN detection.

PMID- 28760629
TI  - Obturator Internus Muscle Endometriosis with Nerve Involvement: a Rare Clinical
      Presentation.
AB  - STUDY OBJECTIVE: To describe our surgical approach in a rare case of deep
      infiltrating endometriosis of the obturator internus muscle with obturator nerve
      involvement. DESIGN: A step-by-step surgical explanation using video and
      literature review (Canadian Task Force Classification III). SETTING:
      Endometriosis can be pelvic or rarely extrapelvic and is classically defined as
      the presence of endometrial glands and stroma outside the uterine cavity [1,2].
      Pain along the sensitive area of the obturator nerve, thigh adduction weakness
      and difficulty in ambulation are extremely rare presenting symptoms [2-4].
      PATIENT: We report a case of a 32-year-old patient who presented with cyclic leg
      pain in the inner right thigh radiating to the knee caused by a cystic
      endometriotic mass in the obturator internus muscle with nerve retraction. The
      patient provided informed consent to use the surgical video. Institutional review
      board approval was obtained. INTERVENTIONS: Pelvic magnetic resonance imaging was
      performed and confirmed a nodular lesion of about 2.3 cm with high signal on T1WI
      and T2WI and without fat suppression on T2FS inside the right obturator internus
      muscle, suggesting an endometriotic lesion (Fig. 1). Surgical removal of the mass
      was performed using the laparoscopic approach. A normal pelvic cavity was found,
      and the retroperitoneal space was dissected. A mass located within the right
      obturator internus muscle, below the right iliac external vein, behind the corona
      mortis vein, and lateral to the right obturator nerve was identified. The whole
      region was inflamed, and the nerve was partially involved. Dissection was
      performed carefully with rupture of the tumor, releasing a chocolatelike fluid
      (Fig. 2), and the cyst was removed. Pathology examination was consistent with
      endometriosis. Patient improvement was observed, with pain relief and improved
      ability for right limb mobilization. No recurrence of endometriosis was found at
      the follow-up visit 6 months later. MEASUREMENTS AND MAIN RESULTS: The obturator
      nerve is responsible for motor and sensitive innervation of the joins and
      internal muscles of thigh and knee as well as the innervation of skin in the
      internal thigh. Pain along the sensitive area of the obturator nerve at the time
      of menstruation, thigh adduction weakness, difficulty ambulating, or paresthesia
      can be presenting symptoms with the involvement of the obturator nerve [5].
      Besides paresthesia, our patient presented all the symptoms. The suspected
      diagnosis of obturator internus muscle endometriosis with retraction of the
      obturator nerve was confirmed by laparoscopic surgery and pathological
      examination of the excised tissue. To our knowledge, only 4 cases of
      endometriosis involving the obturator nerve have been described (according to
      MEDLINE searched in January 2017) [5-8]. The laparoscopic approach provided an
      excellent access to the retroperitoneal space, allowing fine dissection of the
      obturator nerve and the surrounding structures with complete removal of the
      cystic mass. CONCLUSION: We report a rare case of endometriosis with a single
      mass located inside the right obturator internus muscle with neuronal involvement
      of the obturator nerve. The fundamental role of laparoscopy was clearly
      demonstrated for the diagnosis and treatment of our patient.

PMID- 28760630
TI  - Predictors and implications of unplanned conversion during minimally invasive
      hepatectomy: an analysis of the ACS-NSQIP database.
AB  - BACKGROUND: Minimally-invasive hepatectomy (MIH) is increasingly utilized;
      however, predictors and outcomes for patients requiring conversion to an open
      procedure have not been adequately studied. METHODS: The 2014-15 ACS-NSQIP
      database was analyzed. Unplanned conversion was compared to successful MIH and
      elective open hepatectomy. RESULTS: Among 6918 hepatectomies, 1062 (15.4%)
      underwent attempted MIH: 989 laparoscopic, 73 robotic. Conversion occurred in 203
      (19.1%). Compared to successful MIH, patients requiring unplanned conversion
      experienced higher rates of complications (34.5% vs 14.6%, p<0.001), including
      bile leaks (7.4% vs 2.8%, p=0.002), organ space infection (6.4% vs 2.9%,
      p=0.016), UTI (4.9% vs 1.2%, p=0.002), perioperative bleeding (21.2% vs 6.1%,
      p<0.001), DVT (3.0% vs 0.8%, p=0.024), and sepsis (5.9% vs 1.9%, p=0.001).
      Conversion led to greater LOS (5 days vs 3 days, p<0.001) and 30-day mortality
      (3.0% vs 0.5%, p=0.005). Compared to elective open hepatectomy, conversion was
      associated with greater perioperative bleeding (21.2% vs 15.3%, p = 0.037). On
      multivariate analysis, major hepatectomy (OR 2.21, p<0.001), concurrent ablation
      (OR 1.79, p=0.020), and laparoscopic approach (vs. robotic) (OR 3.22, p=0.014)
      were associated with conversion. CONCLUSION: Analysis of this national database
      revealed unplanned conversion during MIH is associated with greater morbidity and
      mortality. MIH should be approached cautiously in patients requiring major
      hepatectomy.

PMID- 28760632
TI  - Effect of Preoperative Urodynamic Detrusor Underactivity on Transurethral Surgery
      for Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis.
AB  - PURPOSE: We investigated the effect of preoperative urodynamic detrusor
      underactivity on the transurethral surgery outcomes of benign prostatic
      hyperplasia. MATERIALS AND METHODS: We systematically searched the online
      PubMed(r), Embase(r) and Cochrane Library databases for articles published
      between January 1989 and June 2017. RESULTS: A total of 10 articles met the
      eligibility criteria for this systematic review. The eligible studies included a
      total of 1,113 patients with a median of 73 per study (range 40 to 382). Five of
      the 10 studies involved conventional transurethral prostatectomy and 5 described
      laser surgery. In patients with detrusor underactivity the pooled mean difference
      was significant for the poorer I-PSS (International Prostate Symptom Score)
      (pooled mean difference -3.73, 95% CI -5.65--1.80 for 9 studies and 936
      participants) and maximal flow rate improvement (pooled mean difference -3.92,
      95% CI -4.85--3.00 for 8 studies and 951 participants) but not for quality of
      life score (pooled mean difference -0.15, 95% CI -0.56-0.25 for 7 studies and 858
      participants) or post-void residual volume (pooled mean difference -5.57, 95% CI 
      20.65-9.50 for 9 studies and 971 participants). Some comparisons showed
      interstudy heterogeneity despite strict selection criteria for the included
      studies. However, there was no clear evidence of publication bias in this meta
      analysis. CONCLUSIONS: Our meta-analysis results showed that preoperative
      detrusor underactivity correlated with poorer I-PSS and maximal flow rate
      improvement. Preoperative urodynamic detrusor underactivity is a valuable finding
      for excluding patients who are inappropriate candidates for transurethral
      surgery.

PMID- 28760633
TI  - Endoscopy in the twenty-first century: minimally invasive state-of-the-art
      medical technology or a future main vector of hospital-acquired infections?

PMID- 28760631
TI  - Prospective comparison of gadoxetic acid-enhanced liver MRI and contrast-enhanced
      CT with histopathological correlation for preoperative detection of colorectal
      liver metastases following chemotherapy and potential impact on surgical plan.
AB  - OBJECTIVE: To prospectively compare the diagnostic performance of gadoxetic acid
      enhanced MRI (EOB-MRI) and contrast-enhanced CT (CECT) for preoperative detection
      of colorectal liver metastases (CRLM) following chemotherapy and to evaluate the
      potential change in the hepatic resection plan. METHODS: 51 patients with CRLM
      treated with preoperative chemotherapy underwent liver imaging by EOB-MRI and
      CECT prospectively. Two independent blinded readers characterized hepatic lesions
      on each imaging modality using a 5-point scoring system. 41 patients underwent
      hepatic resection and histopathological evaluation. RESULTS: 151 CRLM were
      confirmed by histology. EOB-MRI, compared to CECT, had significantly higher
      sensitivity in detection of CRLM <=1.0 cm (86% vs. 45.5%; p < 0.001),
      significantly lower indeterminate lesions diagnosis (7% vs. 33%; p < 0.001) and
      significantly higher interobserver concordance rate in characterizing the lesions
      <=1.0 cm (72% vs. 51%; p = 0.041). The higher yield of EOB-MRI could have changed
      the surgical plan in 45% of patients. CONCLUSION: Following preoperative
      chemotherapy, EOB-MRI is superior to CECT in detection of small CRLM (<=1 cm)
      with significantly higher sensitivity and diagnostic confidence and interobserver
      concordance in lesion characterization. This improved diagnostic performance can
      alter the surgical plan in almost half of patients scheduled for liver resection.

PMID- 28760634
TI  - Tracking the spread routes of opportunistic premise plumbing pathogens in a
      haematology unit with water points-of-use protected by antimicrobial filters.
AB  - BACKGROUND: Water networks in hospitals are frequently contaminated by
      opportunistic premise plumbing pathogens (OPPPs) leading to installation of
      antimicrobial filters on water points-of-use (POU) in order to limit patients'
      exposure. AIM: To assess the spread of OPPPs through secondary water routes
      (outside the plumbing system) in an adult haematology unit in which 52 out of 73
      water POU were high risk for patients and protected by antimicrobial filters.
      METHODS: An observational audit identified six secondary water routes for which
      bacteria tracking and typing were performed in 315 surface samplings. Bacterial
      isolates were identified by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry and compared to the infra-species level by multiplex
      repetitive element sequence-based polymerase chain reaction and/or by restriction
      fragment length polymorphism in pulse-field gel electrophoresis. FINDINGS:
      Pseudomonas aeruginosa and Stenotrophomonas maltophilia, as well as non
      pathogenic OPPP indicators, were detected in water collected upstream of
      antimicrobial filters. P. aeruginosa was the sole OPPP retrieved from tested
      surfaces (5.1%). The same clone of P. aeruginosa spread from water source to dry
      surfaces in the same room and cross-contaminated two sinks in different rooms.
      Three clones of non-pathogenic OPPP indicators spread more widely in different
      rooms. CONCLUSION: A strategy based on filtration of most (but not all) water POU
      in a haematology unit could be sufficient to limit the spread of OPPPs to the
      environment, provided a functional mapping of 'high-risk' POU has been
      undertaken. The residual spread of OPPPs and OPPP indicators linked to non
      filtered water POU argues for careful monitoring of non-filtered water use.

PMID- 28760635
TI  - The potential of alcohol release doorplates to reduce surface contamination
      during hand contact.
AB  - BACKGROUND: Optimal hand hygiene may be compromised by contact with contaminated
      environmental surfaces. AIM: To investigate the in-vitro efficacy of a novel
      alcohol-release doorplate to reduce surface contamination during hand contact.
      METHODS: Prototype, horizontally held, Surfaceskins, alcohol gel-impregnated and
      control (aluminium) doorplates were challenged (N = 72 per micro-organism) with
      Staphylococcus aureus-, Eschericia coli-, Enterococcus faecalis-, or Clostridium
      difficile-contaminated fingers. S. aureus and E. faecalis were used for
      challenges (90 per micro-organism) of vertical (modified design) doorplates, on
      days 0, 3, 4, 6, and 7. Surface contamination was measured pre and immediately
      post challenges using agar contact plates. FINDINGS: Horizontal test, but not
      control, doorplates demonstrated bacterial killing of S. aureus, E. faecalis and
      E. coli, but not of C. difficile; hence, only testing of S. aureus and E.
      faecalis was continued. Vertical Surfaceskins, but not control, doorplates
      demonstrated rapid killing of S. aureus over seven days. There were significant
      reductions (>90% up to day 6; P <= 0.01) of surface bacterial colony counts
      compared with controls immediately post challenge. There were also significant
      reductions in Surfaceskins doorplate enterococcal colony counts compared with
      controls on every day of testing (P <= 0.004). There was no evidence that
      bacterial recovery was greater from the tops of Surfaceskins doorplates (i.e. due
      to pooling of contents). CONCLUSION: Surfaceskins doorplates were efficient at
      reducing surface contamination by S. aureus, E. faecalis, and E. coli. Reducing
      microbial contamination of frequently touched door surfaces, and so bacterial
      transfer via hands, could feasibly reduce the risk of healthcare-associated and
      other infections.

PMID- 28760636
TI  - Changing the paradigm: messages for hand hygiene education and audit from cluster
      analysis.
AB  - BACKGROUND: Hand hygiene is considered to be the foremost infection prevention
      measure. How healthcare workers accept and make sense of the hand hygiene message
      is likely to contribute to the success and sustainability of initiatives to
      improve performance, which is often poor. METHODS: A survey of nurses in critical
      care units in three National Health Service trusts in England was undertaken to
      explore opinions about hand hygiene, use of alcohol hand rubs, audit with
      performance feedback, and other key hand-hygiene-related issues. Data were
      analysed descriptively and subjected to cluster analysis. RESULTS: Three main
      clusters of opinion were visualized, each forming a significant group: positive
      attitudes, pragmatism and scepticism. A smaller cluster suggested possible guilt
      about ability to perform hand hygiene. CONCLUSION: Cluster analysis identified
      previously unsuspected constellations of beliefs about hand hygiene that offer a
      plausible explanation for behaviour. Healthcare workers might respond to
      education and audit differently according to these beliefs. Those holding
      predominantly positive opinions might comply with hand hygiene policy and perform
      well as infection prevention link nurses and champions. Those holding pragmatic
      attitudes are likely to respond favourably to the need for professional behaviour
      and need to protect themselves from infection. Greater persuasion may be needed
      to encourage those who are sceptical about the importance of hand hygiene to
      comply with guidelines. Interventions to increase compliance should be
      sufficiently broad in scope to tackle different beliefs. Alternatively, cluster
      analysis of hand hygiene beliefs could be used to identify the most effective
      educational and monitoring strategies for a particular clinical setting.

PMID- 28760637
TI  - Analysis of the life stages of Cimex lectularius captured within a medical centre
      suggests that the true numbers of bed bug introductions are under-reported.
AB  - Little is known about the epidemiology of bed bugs within the healthcare system,
      but nymphal stages predominate in natural infestations. This study determined the
      life stages of bed bugs captured within a medical centre, and found that older
      bed bugs were more likely to be captured than younger insects. The numbers of
      first instars, third-fifth instars and adult females captured were significantly
      different compared with the numbers of each life stage found in a natural
      infestation (P<0.01). A significant number of early-instar bed bugs introduced
      into the medical centre may go unnoticed by hospital staff.

PMID- 28760638
TI  - The impact of autologous breast reconstruction using DIEP flap on the oncologic
      efficacy of radiation therapy.
AB  - INTRODUCTION: In the management of breast cancer radiation therapy plays a
      substantive role in decreasing local recurrence and increasing overall survival.
      Still, there exists controversy concerning compromised radiation delivery plans
      and suboptimal delivery after immediate autologous breast reconstruction. Our
      study aims to assess the oncologic safety of immediate breast reconstruction
      (IBR) with a Deep inferior epigastric perforator flap (DIEP), in the setting of
      adjuvant radiation therapy. METHODS: We conducted a retrospective analysis using
      a prospectively maintained database of all consecutive women undergoing breast
      reconstruction with a DIEP flap in the setting of radiation therapy. Independent
      variables included patient age, cancer stage, tumor grade type and subtype,
      adjuvant and neoadjuvant chemotherapy, hormonal therapy, diabetes mellitus, and
      tobacco use. Main outcome variables were: local recurrence, distant metastasis,
      patient demise and total flap failure. RESULTS: From July 2008 to January 2014,
      and out of 450 patients who underwent reconstruction with a DIEP flap, 62 were
      considered eligible. Thirty patients (48%) had IBR followed by radiation therapy
      and 32 (52%) had delayed reconstruction preceded by radiation therapy. The two
      groups were comparable with respect to the independent variables. Local
      recurrence occurred in 3.2% of patients; 3.3% in the immediate group and 3.1% in
      the delayed (P=0.963). Distant metastasis occurred in 6.4% of patients: 10% in
      the immediate group and 3.1% in the delayed (P=0.27). Breast cancer related
      mortality occurred in 4.8%: 6.7% in the immediate group and 3.1% in the delayed
      (P=0.52). CONCLUSION: Immediate reconstruction with a DIEP flap in the setting of
      adjuvant radiation therapy is an acceptable approach and appears not to influence
      the oncologic efficacy of radiation treatment. Further prospective studies are
      advocated.

PMID- 28760639
TI  - The Association Between Glaucoma, Anxiety, and Depression in a Large Population.
AB  - PURPOSE: To investigate the association between glaucoma and each of anxiety and
      depression. DESIGN: Retrospective case-control study. METHODS: Settings:
      University of North Carolina hospitals and outpatient clinics. STUDY POPULATION:
      All patients over the age of 18 years seen between July 1, 2008 and October 1,
      2015 were included. OBSERVATION PROCEDURE: International Classification of
      Diseases codes were used to identify cases of glaucoma, as well as anxiety and
      depression. OUTCOME MEASURE: Odds ratios (OR) were calculated for glaucoma and
      each of anxiety and depression. OR were also calculated for above diagnoses
      separated by age group and sex. RESULTS: A total of 4 439 518 patients were
      screened, of which 11 234 (0.3%) have glaucoma, 96 527 (2.2%) have anxiety, and
      103 476 (2.3%) have depression. The adjusted OR was 10.6 (95% confidence interval
      [CI] 10.0-11.0) for glaucoma and anxiety and 12.3 (95% CI 11.8-12.9) for glaucoma
      and depression. The likelihood of having anxiety and depression along with
      glaucoma did not change with age (P = .088, P = .736). CONCLUSION: There was a
      statistically significant association between glaucoma and each of anxiety and
      depression.

PMID- 28760640
TI  - Sialidase NEU3 defines invasive potential of human glioblastoma cells by
      regulating calpain-mediated proteolysis of focal adhesion proteins.
AB  - BACKGROUND: Glioblastoma multiforme is one of the most malignant tumors of the
      human central nervous system characterized by high degree of invasiveness.
      Focusing on this invasive nature, we investigated whether ganglioside-specific
      sialidase NEU3 might be involved, because gangliosides are major components of
      brain tissues, and cell surface sialic acids, as target residues of sialidase
      catalysis, are thought to be closely related to cell invasion. METHODS: NEU3 mRNA
      levels of human glioblastoma specimens were evaluated by quantitative RT-PCR.
      Human glioblastoma cell lines, U251, A172, and T98G were used for cell invasion
      and migration by transwell and cell scratching assay. The molecules involved in
      the signaling cascade were investigated by western blot and immunofluorescent
      microscopy. RESULTS: NEU3 expression was down-regulated in human glioblastoma
      specimens. In the human glioblastoma cell lines, NEU3 overexpression reduced
      invasion and migration by promoting the assembly of focal adhesions through
      reduced calpain-dependent proteolysis, but NEU3 silencing resulted in
      accelerating cell invasion via disassembly of focal adhesions. In NEU3-silenced
      cells, elevation of calpain activity and GM3 accumulation were observed, as
      results of reduced sialidase hydrolysis, localization of calpain and GM3 at the
      cell lamellipodium being demonstrated by immunofluorescence microscopy.
      CONCLUSION: Sialidase NEU3 was found to exert a great influence on cell invasion
      in regulation of calpain activity and focal adhesion disassembly and consequent
      invasive potential of glioblastoma cells. GENERAL SIGNIFICANCE: This first
      demonstration of sialidase involvement in invasive potential of gliolastoma cells
      may point to NEU3 as an attractive treatment target of human gliomas.

PMID- 28760641
TI  - Maternal alterations induced by exposure to an unfamiliar home cage in early
      underfed dams.
AB  - The expression of different behavioral components in the adult rat depends on a
      number of early influences, including age, hormones, manipulations of sensory
      cues, and perinatal undernutrition, all of which impact the development of brain
      areas underlying adaptive processes, maternal behavior, and the response to
      novelty. The current study investigates the effects of pre- and neonatal
      undernutrition on various components of maternal behavior of dams exposed to the
      challenge of an unfamiliar home cage on days 4, 8, and 12 of lactation. Food
      restriction was initiated from gestational day (G) G6 to G19 when dams received
      50-70% of the normal balanced diet, followed by 100% from G20 to G21. After
      birth, pups were underfed by alternating every 12h between two lactating dams,
      one of which, had ligated nipples. Weaning was at 25days of age followed by an ad
      libitum diet until postpartum day 90, when females were mated, and subsequently
      tested for maternal behavior in an unfamiliar cage. The results indicated that in
      early underfed mothers the frequency of handling wood shavings and of,
      approaching, licking, crouching, and grasping pups for retrieval was
      significantly reduced. Moreover, self-grooming increased substantially in the
      underfed dams, but the frequency of rearing was reduced. Additionally, the body
      weight of pups nursed by early underfed dams was significantly lower than that of
      control pups. These findings suggest a relation between early food restriction
      and the deficient maternal care observed when these dams were challenged by
      exposure to an unfamiliar home cage.

PMID- 28760642
TI  - Galantamine administration reduces reactive astrogliosis and upregulates the anti
      oxidant enzyme catalase in rats submitted to neonatal hypoxia ischemia.
AB  - Neonatal hypoxia ischemia (HI) plays a role in the etiology of several
      neurological pathologies and causes severe sequelae. Acetylcholine is a
      neurotransmitter in the central nervous system and cholinesterase inhibitors have
      demonstrated a positive action over HI induced deficits. In order to evaluate the
      effects of pre and post-hypoxia administrations of galantamine, a cholinesterase
      inhibitor, in a model of perinatal HI, Wistar rats in the post-natal day 7 (PND7)
      were subjected to a combination of unilateral occlusion of the right carotid
      artery with the exposure to a 1h hypoxia. Intraperitoneal injections of
      galantamine were administered in two different protocols: one pre and other post
      hypoxia. The analysis of brain structures volume at PND45 showed that pre-hypoxia
      galantamine treatment prevented tissue injury to the ipsilesional hippocampus.
      Also, immunofluorescence showed HI-induced increase in the number of astrocytes
      that was prevented by pre-hypoxia treatment. Biochemical analysis was performed
      in the ipsilesional hippocampus at PND8 and revealed that pre-hypoxia galantamine
      treatment: 1) prevented the neuronal loss induced by HI; 2) reduced the HI
      induced hypertrophy of astrocytes; and 3) caused an increase in the activity of
      the anti-oxidant enzyme catalase. Overall, treatment with galantamine was able to
      prevent the brain damage, increase the survival of neurons, reduce astrocytic
      reaction and increase the activity of the anti-oxidant enzyme catalase in rats
      submitted to neonatal hypoxia ischemia.

PMID- 28760644
TI  - Why Has a Run-In Period Been a Design Element in Most Landmark Clinical Trials?
      Analysis of the Critical Role of Run-In Periods in Drug Development.
AB  - Prior exposure to one of the randomized treatments has been a routine design
      element of large-scale trials in patients at high cardiovascular risk. A run-in
      feature has allowed our trials to be more realistic; it has strengthened their
      ability to estimate the true treatment effect; and it has never undermined the
      validity of a trial's findings. Those who suggest that run-in periods distort the
      results of large-scale trials should become more familiar with our history of
      drug development and our standards of clinical practice. Physicians use run-in
      periods every day in real life, and trialists have used run-in periods for
      decades to reliably establish the role of new cardiovascular drugs. Those who
      reflexively criticize the trials because of their inclusion of a run-in period
      need to carefully reexamine how medicine is practiced and how it advances.

PMID- 28760643
TI  - Reactive oxygen species, oxidative stress, glaucoma and hyperbaric oxygen
      therapy.
AB  - This review examines the role of oxidative stress in damage to cells of the
      trabecular meshwork and associated impaired aqueous drainage as well as damage to
      retinal ganglion cells and associated visual field losses. Consideration is given
      to the interaction between vascular and mechanical explanations for pathological
      changes in glaucoma. For example, elevated intraocular pressure (IOP) forces may
      contribute to ischaemia but there is increasing evidence that altered blood flow
      in a wider sense is also involved. Both vascular and mechanical theories are
      involved through fluctuations in intraocular pressure and dysregulation of blood
      flow. Retinal function is very sensitive to changes in haemoglobin oxygen
      concentration and the associated variations in the production of reactive oxygen
      species. Reperfusion injury and production of reactive oxygen species occurs when
      IOP is elevated or blood pressure is low and beyond the capacity for blood flow
      autoregulation to maintain appropriate oxygen concentration. Activities such as
      those associated with postural changes, muscular effort, eye wiping and rubbing
      which cause IOP fluctuation, may have significant vascular, mechanical,
      reperfusion and oxidative stress consequences. Hyperbaric oxygen therapy exposes
      the eye to increased oxygen concentration and the risk of oxidative damage in
      susceptible individuals. However, oxygen concentration in aqueous humour, and the
      risk of damage to trabecular meshwork cells may be greater if hyperbaric oxygen
      is delivered by a hood which exposes the anterior ocular surface to higher than
      normal oxygen levels. Oronasal mask delivery of hyperbaric oxygen therapy appears
      to be indicated in these cases.

PMID- 28760645
TI  - Influence of Prior Tyrosine Kinase Inhibitor on Survival for Patients with
      Metastatic Renal Cell Carcinoma Treated with Nivolumab or Cabozantinib: Data from
      a Literature-based Meta-analysis.

PMID- 28760646
TI  - Determinants of Patient Mobility for Prostate Cancer Surgery: A Population-based
      Study of Choice and Competition.
AB  - : Many countries have introduced policies that enable patients to select a health
      care provider of their choice with the aim of improving the quality of care.
      However, there is little information about the drivers or the impact of patient
      mobility. Using administrative hospital data (n=19256) we analysed the mobility
      of prostate cancer patients who had radical surgery in England between 2010 and
      2014. Our analysis, using geographic information systems and multivariable choice
      modelling, found that 33.5% (n=6465) of men bypassed their nearest prostate
      cancer surgical centre. Travel time had a strong impact on where patients moved
      to but was less of a factor for men who were younger, fitter, and more affluent
      (p always < 0.001). Men were more likely to move to hospitals that provided
      robotic prostate cancer surgery (odds ratio: 1.42, p<0.001) and to hospitals that
      employed surgeons with a strong media reputation (odds ratio: 2.18, p<0.001).
      Patient mobility occurred in the absence of validated measures of the quality of
      care, instead influenced by the adoption of robotic surgery and the reputation of
      individual clinicians. National policy based on patient choice and provider
      competition may have had a negative impact on equality of access, service
      capacity, and health system efficiency. PATIENT SUMMARY: In this study, we
      assessed the reasons why men would choose to have prostate cancer surgery at a
      centre other than their nearest. We found that in England men were attracted to
      centres that carried out robotic surgery and employed surgeons with a national
      reputation.

PMID- 28760647
TI  - What do we actually hope to accomplish by modeling art experience?: Reply to
      comments on "Move me, astonish me... delight my eyes and brain: The Vienna
      Integrated Model of top-down and bottom-up processes in Art Perception (VIMAP)
      and corresponding affective, evaluative, and neurophysiological correlates".

PMID- 28760648
TI  - Racial and Socioeconomic Disparities in Disabling Chronic Pain: Findings From the
      Health and Retirement Study.
AB  - : The U.S. National Pain Strategy calls for increased population research on
      "high-impact chronic pain" (ie, longstanding pain that substantially limits
      participation in daily activities). Using data from the nationally-representative
      Health and Retirement Study (HRS), we investigated the prevalence of high-impact
      chronic pain in U.S. adults older than age 50 overall and within population
      subgroups. We also explored sociodemographic variation in pain-related disability
      within specific activity domains. Data are from a subsample of HRS respondents (n
      = 1,925) who were randomly selected for a supplementary pain module in 2010. Our
      outcome was operationalized as pain duration of >=7 months and a disability
      rating of >=7 (0-10 scale) in at least 1 domain: family/home, leisure, social
      activities, work, or basic activities. Overall, 8.2% (95% confidence interval =
      6.7-10.1%) of adults older than age 50 met criteria for high-impact chronic pain.
      This proportion rose to 17.1% (95% confidence interval = 12.3-23.4%) among
      individuals in the lowest wealth quartile. Prevalence differences according to
      education, race/ethnicity, and age were not significant. Arthritis and depression
      were significantly associated with high-impact pain in multivariable analysis.
      Among adults with any chronic pain, African American and individuals in the
      lowest wealth quartile reported more pain-related disability across activity
      domains. PERSPECTIVE: High-impact chronic pain is unequally distributed among
      midlife and older U.S. adults. Efforts to reduce the burden of disabling chronic
      pain should prioritize socioeconomically vulnerable groups, who may have the
      least access to multimodal pain treatment to improve function.

PMID- 28760649
TI  - Ribavirin and boceprevir are able to reduce Canine distemper virus growth in
      vitro.
AB  - Canine distemper virus (CDV) is a major infectious disease of dogs. Although
      vaccines were successful to control CDV spread in canine population, the disease
      is still common and may pose a threat to unvaccinated dogs. In the attempt to
      develop specific anti-viral therapeutic tools, the efficacy of several molecules
      against CDV has been investigated in vitro. In this study the antiviral efficacy
      in vitro against CDV of ribavirin and boceprevir alone or in combination was
      evaluated. CDV growth in VERO cells was inhibited by ribavirin, by boceprevir and
      by a combination of the two molecules at non-cytotoxic concentrations, as
      evaluated by end-point viral titration in cell monolayers and by quantification
      of viral RNA using quantitative RT-PCR. By end-point titration, a statistically
      significant reduction in CDV replication was observed only using ribavirin and
      boceprevir in combination. By quantitative RT-PCR, a significant reduction of
      viral growth was observed either in cells treated with ribavirin or boceprevir or
      with both the two molecules. The association of ribavirin or boceprevir was able
      to decrease CDV growth by up to 3.4458 logs with respect to untreated infected
      cells, chiefly at the highest virus dilutions. The results obtained in this study
      may constitute an important basis for the development of CDV therapies.

PMID- 28760650
TI  - Grip strength in mice with joint inflammation: A rheumatology function test
      sensitive to pain and analgesia.
AB  - Grip strength deficit is a measure of pain-induced functional disability in
      rheumatic disease. We tested whether this parameter and tactile allodynia, the
      standard pain measure in preclinical studies, show parallels in their response to
      analgesics and basic mechanisms. Mice with periarticular injections of complete
      Freund's adjuvant (CFA) in the ankles showed periarticular immune infiltration
      and synovial membrane alterations, together with pronounced grip strength
      deficits and tactile allodynia measured with von Frey hairs. However,
      inflammation-induced tactile allodynia lasted longer than grip strength
      alterations, and therefore did not drive the functional deficits. Oral
      administration of the opioid drugs oxycodone (1-8 mg/kg) and tramadol (10-80
      mg/kg) induced a better recovery of grip strength than acetaminophen (40-320
      mg/kg) or the nonsteroidal antiinflammatory drugs ibuprofen (10-80 mg/kg) or
      celecoxib (40-160 mg/kg); these results are consistent with their analgesic
      efficacy in humans. Functional impairment was generally a more sensitive
      indicator of drug-induced analgesia than tactile allodynia, as drug doses that
      attenuated grip strength deficits showed little or no effect on von Frey
      thresholds. Finally, ruthenium red (a nonselective TRP antagonist) or the in vivo
      ablation of TRPV1-expressing neurons with resiniferatoxin abolished tactile
      allodynia without altering grip strength deficits, indicating that the
      neurobiology of tactile allodynia and grip strength deficits differ. In
      conclusion, grip strength deficits are due to a distinct type of pain that
      reflects an important aspect of the human pain experience, and therefore merits
      further exploration in preclinical studies to improve the translation of new
      analgesics from bench to bedside.

PMID- 28760651
TI  - Evaluation of urinary autophagy transcripts expression in diabetic kidney
      disease.
AB  - BACKGROUND: We identified and validated novel urinary autophagy markers in
      diabetic kidney disease (DKD) based on bioinformatics analysis and clinical
      validation. PATIENTS & METHODS: We retrieved three novel autophagy genes related
      to DKD from public microarray databases, namely; microtubule-associated protein
      light chain (MAP1LC3A), WD Repeat Domain, Phosphoinositide Interacting 2 (WIPI2),
      and RB1-Inducible Coiled-Coil 1 (RB1CC1). Secondly we assessed the expression of
      the chosen autophagy transcript in urine sediment of 86 patients with DKD and 74
      (age and sex matched) controls by reverse transcription quantitative real-time
      PCR. RESULTS: The urinary expression levels of MAP1LC3A, WIPI, RB1CC1 were
      significantly lower in DKD than control group (P<0.001).The receiver-operating
      characteristic curve (ROC) analyses that each urinary autophagy transcript showed
      high sensitivity and specificity for distinguishing DKD from control (MAP1LC3A,
      81.4% and 81.1%; WIPI, 74.4% and 67.6%, and RB1CC1, 81.4%,70.3%, respectively).
      Notably, a negative correlation was found between these autophagy markers, serum
      creatinine and urinary albumin creatinine ratio. The sensitivity and specificity
      of this urinary autophagy based panel reached 90.6% and 60% in diagnosis of DKD.
      CONCLUSION: We identified and validated a novel diagnostic urinary autophagy
      based panel with high sensitivity and moderate specificity representing a vital
      player in the pathogenesis of DKD.

PMID- 28760653
TI  - Successful treatment of pituitary sella Aspergillus abscess in a renal transplant
      recipient.

PMID- 28760652
TI  - Serum amyloid A enrichment impairs the anti-inflammatory ability of HDL from
      diabetic nephropathy patients.
AB  - AIMS: Impaired anti-inflammatory ability of high-density lipoprotein (HDL) has
      been demonstrated in patients with type-2 diabetes mellitus (T2DM). However,
      whether HDL from patients with diabetic nephropathy (DN) suffers additional
      damage remains unknown. This study compared the anti-inflammatory capacities of
      HDL from healthy controls, T2DM patients with normal renal function, and T2DM
      patients with DN. MATERIALS AND METHODS: HDL was isolated from healthy controls
      (n=33) and T2DM patients with normal renal function (n=21), chronic kidney
      disease (CKD) (n=27), and end-stage renal disease (ESRD) (n=27). Human peripheral
      blood mononuclear cells (PBMCs) from healthy volunteers were pretreated with HDL
      (100MUg/mL) for 1h, then incubated with lipopolysaccharide (LPS) (50ng/mL) for
      24h. The anti-inflammatory ability of HDL was measured as the secretion of TNF
      alpha in LPS-activated monocytes. RESULTS: The anti-inflammatory ability of HDL
      was gradually impaired as kidney function declined. Serum amyloid A (SAA)
      concentration in HDLDN significantly increased and was positively correlated with
      the impaired anti-inflammatory ability of HDL (Pearson r=0.315, P=0.006).
      Furthermore, HDL supplemented with SAA significantly increased TNF-alpha release
      from PBMCs compared with that from control HDL. CONCLUSIONS: These findings
      identified an impaired anti-inflammatory capacity of HDL from DN patients, which
      might be attributable to SAA enrichment.

PMID- 28760654
TI  - Surgical outcome of thoracic myelopathy caused by ossification of ligamentum
      flavum.
AB  - Ossification of the ligamentum flavum (OLF) may result in thoracic myelopathy
      (TM) because of the spinal canal narrowing. The aim of this study was to
      investigate clinical outcomes of symptomatic thoracic OLF treated using posterior
      decompressive laminectomy. We made a retrospective review of patients who
      underwent posterior decompressive laminectomy from 2007 through 2016 for
      symptomatic TM caused by OLF. Thirty-three patients who had surgery for TM caused
      by OLF that was diagnosed based on clinical, radiologic, and pathologic
      evaluations. All patients had undergone decompressive laminectomy and excision of
      the OLF. The clinical course was evaluated according to modified JOA scores.
      Magnetic resonance imaging was used to determine the number of vertebral segments
      demonstrating OLF, the level of thoracic cord involvement, and spine lesions
      coexisting with OLF. Results showed the neurological status improved at follow up
      (70.82+/-32.22months) from a preoperative mean Japanese Orthopaedic Association
      score of 7.03+/-1.29 points to 9.52+/-0.83 points at the last follow up (p<0.01).
      Recovery outcomes were excellent in 8 patients, good in 22 patients, fair in 2
      patients and poor in 1 patient. Surgical complications, which resolved after
      appropriate and prompt treatment, including cerebrospinal fluid leakage in 4
      patient, immediate postoperative neurologic deterioration in 2 patient, and wound
      infection in 4 patient. Our findings suggest that posterior decompressive
      laminectomy with or without instrumented fusion is an effective treatment for
      symptomatic thoracic OLF, which provides satisfactory clinical improvement.

PMID- 28760655
TI  - The peroxisomal import receptor PEX5 functions as a stress sensor, retaining
      catalase in the cytosol in times of oxidative stress.
AB  - Accumulating evidence indicates that peroxisome functioning, catalase
      localization, and cellular oxidative balance are intimately interconnected.
      Nevertheless, it remains largely unclear why modest increases in the cellular
      redox state especially interfere with the subcellular localization of catalase,
      the most abundant peroxisomal antioxidant enzyme. This study aimed at gaining
      more insight into this phenomenon. Therefore, we first established a simple and
      powerful approach to study peroxisomal protein import and protein-protein
      interactions in living cells in response to changes in redox state. By employing
      this approach, we confirm and extend previous observations that Cys-11 of human
      PEX5, the shuttling import receptor for peroxisomal matrix proteins containing a
      C-terminal peroxisomal targeting signal (PTS1), functions as a redox switch that
      modulates the protein's activity in response to intracellular oxidative stress.
      In addition, we show that oxidative stress affects the import of catalase, a non
      canonical PTS1-containing protein, more than the import of a reporter protein
      containing a canonical PTS1. Furthermore, we demonstrate that changes in the
      local redox state do not affect PEX5-substrate binding and that human PEX5 does
      not oligomerize in cellulo, not even when the cells are exposed to oxidative
      stress. Finally, we present evidence that catalase retained in the cytosol can
      protect against H2O2-mediated redox changes in a manner that peroxisomally
      targeted catalase does not. Together, these findings lend credit to the idea that
      inefficient catalase import, when coupled with the role of PEX5 as a redox
      regulated import receptor, constitutes a cellular defense mechanism to combat
      oxidative insults of extra-peroxisomal origin.

PMID- 28760656
TI  - Norcantharidin induces mitochondrial-dependent apoptosis through Mcl-1 inhibition
      in human prostate cancer cells.
AB  - Norcantharidin (NCTD) is the demethylated form of cantharidin that exhibits
      anticancer potential in many cancer cell types. Recent reports suggest that NCTD
      targeting ROS/AMPK and DNA replication signaling pathway could be an effective
      strategy for the treatment of PCa cells. However, supportive evidence is limited
      to the effect of NCTD that induction of apoptosis through suppression of the Mcl
      1. Here, we show that NCTD induced PCa cell apoptosis and triggered caspase
      activation, which was associated with mitochondria dysfunction. Mechanistic
      investigations suggested that NCTD modulated the Akt signaling via increased
      nuclear translocation and interaction with the myeloid cell leukemia-1 (Mcl-1)
      promoter by FOXO4, resulting in an apoptotic effect. Moreover, miR-320d, which
      targets Mcl-1, was significantly upregulated after NCTD treatment. Overexpression
      of miR-320d by NCTD induced mitochondria dysfunction and apoptosis, which was
      notably attenuated with a miR-320d inhibitor. In vivo xenograft analysis revealed
      that NCTD significantly reduced tumor growth in mice with PC3 tumor xenografts.
      Taken together, our results provide new insights into the critical role of NCTD
      in suppressing Mcl-1 via epigenetic upregulation of miR-320d, resulting in PCa
      cell apoptosis.

PMID- 28760657
TI  - The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2
      associated factor 35, BRAF35.
AB  - MID1/TRIM18 is a member of the TRIM family of ubiquitin E3 ligases characterized
      by the presence of a conserved RING-containing N-terminal tripartite motif.
      Mutations in the MID1 gene have been associated with the X-linked form of Opitz
      Syndrome, a developmental disorder characterized by midline defects and
      intellectual disability. The effect of MID1 E3 ligase activity within the cell
      and the role in the pathogenesis of the disease is still not completely
      unraveled. Here, we report BRAF35, a non-canonical HMG nuclear factor, as a novel
      MID1 substrate. MID1 is implicated in BRAF35 ubiquitination promoting atypical
      poly-ubiquitination via K6-, K27- and K29-linkages. We observed a partial co
      localization of the two proteins within cytoplasmic bodies. We found that MID1
      depletion alters BRAF35 localization in these structures and increases BRAF35
      stability affecting its cytoplasmic abundance. Our data reveal a novel role for
      MID1 and for atypical ubiquitination in balancing BRAF35 presence, and likely its
      activity, within nuclear and cytoplasmic compartments.

PMID- 28760658
TI  - Frailty, body composition and nutritional status in non-institutionalised
      elderly.
AB  - OBJECTIVE: Frailty is a clinical syndrome characterized, among other signs, by
      involuntary weight loss and decreased muscle strength. The aim of this study was
      to analyse associations between frailty, body composition and nutritional status
      in non-institutionalised elderly people in the municipality of Alfandega
      (Braganza-Portugal). METHOD: Observational, prevalence and association study
      involving 220 elderly (mean 75.8+/-6.8 years of age; 68.8% women). Frailty was
      assessedt according to Fried criteria, body composition by bioelectrical
      impedance analysis and nutritional status using the Mini Nutritional Assessment
      Short-Form. RESULTS: The prevalence of frailty was 23.6%. Frail participants had,
      on average, lower total muscle mass and lower segmental muscle mass (arms and
      legs) than pre-frail and non-frail (p <.001). From the elderly at risk of
      malnutrition or undernourished (n=24), the majority (n=13) had frailty syndrome.
      It was observed that 41.2% of the elderly with low weight were frail. This
      syndrome prevailed only in 17.1% of the eutrophic persons, increasing again to
      22.4% in the overweight group (p <.001). CONCLUSION: The phenotypic profile of
      frail elderly was characterised by lower muscle mass. The results of our study
      suggest that both underweight and overweight may be associated with frailty.
      There is the need to prevent and manage frailty, not only taking into account
      possible treatable medical causes, but also by intervening in important pillars,
      such as physical activity, dietary and nutritional problems.

PMID- 28760659
TI  - No Causal Association between 25-Hydroxyvitamin D and Features of Skin Aging:
      Evidence from a Bidirectional Mendelian Randomization Study.
AB  - Data from in vitro experiments suggest that vitamin D reduces the rate of skin
      aging, whereas population studies suggest the opposite, most likely due to
      confounding by UV exposure. We investigated whether there are causal associations
      between 25-hydroxyvitamin D concentrations and features of skin aging in a
      bidirectional Mendelian randomization study. In the Rotterdam Study (N = 3,831;
      58.2% women, median age 66.5 years) and Leiden Longevity Study (N = 661; 50.5%
      women, median age 63.1 years), facial skin aging features (perceived age,
      wrinkling, pigmented spots) were assessed either manually or digitally.
      Associations between 25-hydroxyvitamin D and skin aging features were tested by
      multivariable linear regression. Mendelian randomization analyses were performed
      using single nucleotide polymorphisms identified from previous genome-wide
      association studies. After meta-analysis of the two cohorts, we observed that
      higher serum 25-hydroxyvitamin D was associated with a higher perceived age (P
      value = 3.6 * 10-7), more skin wrinkling (P-value = 2.6 * 10-16), but not with
      more pigmented spots (P-value = 0.30). In contrast, a genetically determined 25
      hydroxyvitamin D concentration was not associated with any skin aging feature (P
      values > 0.05). Furthermore, a genetically determined higher degree of pigmented
      spots was not associated with higher 25-hydroxyvitamin D (P-values > 0.05). Our
      study did not indicate that associations between 25-hydroxyvitamin D and features
      of skin aging are causal.

PMID- 28760660
TI  - Semaphorin4D Drives CD8+ T-Cell Lesional Trafficking in Oral Lichen Planus via
      CXCL9/CXCL10 Upregulations in Oral Keratinocytes.
AB  - Chemokine-mediated CD8+ T-cell recruitment is an essential but not well
      established event for the persistence of oral lichen planus (OLP). Semaphorin 4D
      (Sema4D)/CD100 is implicated in immune dysfunction, chemokine modulation, and
      cell migration, which are critical aspects for OLP progression, but its
      implication in OLP pathogenesis has not been determined. In this study, we sought
      to explicate the effect of Sema4D on human oral keratinocytes and its capacity to
      drive CD8+ T-cell lesional trafficking via chemokine modulation. We found that
      upregulations of sSema4D in OLP tissues and blood were positively correlated with
      disease severity and activity. In vitro observation revealed that Sema4D induced
      C-X-C motif chemokine ligand 9/C-X-C motif chemokine ligand 10 production by
      binding to plexin-B1 via protein kinase B-NF-kappaB cascade in human oral
      keratinocytes, which elicited OLP CD8+ T-cell migration. We also confirmed using
      clinical samples that elevated C-X-C motif chemokine ligand 9/C-X-C motif
      chemokine ligand 10 levels were positively correlated with sSema4D levels in OLP
      lesions and serum. Notably, we determined matrix metalloproteinase-9 as a new
      proteolytic enzyme for the cleavage of sSema4D from the T-cell surface, which may
      contribute to the high levels of sSema4D in OLP lesions and serum. Our findings
      conclusively revealed an amplification feedback loop involving T cells,
      chemokines, and Sema4D-dependent signal that promotes OLP progression.

PMID- 28760661
TI  - SOX4 Promotes Proliferative Signals by Regulating Glycolysis through AKT
      Activation in Melanoma Cells.
AB  - The sex-determining region Y-related high-mobility group box transcription factor
      4 (SOX4) plays a fundamental role during embryogenesis and controls cell fate and
      differentiation. Recently, increased SOX4 expression has been reported in various
      cancer types, contributing to the progression and survival of cancer cells.
      However, the distinct functions and downstream targets of SOX4 remain to be fully
      elucidated. In this study, we initially found elevated SOX4 expression in
      melanoma. SOX4 regulates apoptosis and cell cycle arrest, affects glucose
      consumption and lactate production, and consequently, promotes melanoma cell
      proliferation. Moreover, we found that SOX4 rewires glucose metabolism by
      regulating the expression of glucose transporter type 1, hexokinase 2, and
      lactate dehydrogenase A at the transcriptional level. Mechanistically, SOX4
      knockdown reduced activation of acutely transforming retrovirus AKT8 in rodent T
      cell lymphoma and mTORC1, leading to an attenuated malignant phenotype. We also
      identified p70 ribosomal S6 kinase and eukaryotic initiation factor 4E-binding
      protein 1 as key substrates involved in the regulation of mTORC1 in melanoma
      cells. In conclusion, our study demonstrates the essential role of SOX4 in
      melanoma glycolytic metabolism through the acutely transforming retrovirus AKT8
      in rodent T-cell lymphoma signaling pathway and highlights its potential as a
      therapeutic target in melanoma management.

PMID- 28760662
TI  - Acute ethanol modulation of neurocircuit function in the nucleus of the tractus
      solitarius.
AB  - The nucleus of the tractus solitarius (NTS) is a brain stem region critical to
      many physiologic processes and has been implicated in addiction to multiple
      classes of abused drugs, including alcohol (EtOH). That said, the mechanism by
      which EtOH modulates NTS neurocircuit activity is not well characterized and has
      yet to be examined utilizing electrophysiologic methods in mouse models of
      alcohol use disorders. To begin to address this gap in knowledge, we sought to
      use whole-cell and cell-attached recordings to determine the mechanism of acute
      EtOH action on GABAergic and glutamatergic neurotransmission, as well as on
      action potential firing in the NTS of adult male, EtOH naive mice. Bath
      application of EtOH (50mM) significantly enhanced the frequency of spontaneous
      inhibitory postsynaptic current events, while increasing the amplitude of these
      events in half of the neurons tested. This finding suggests a presynaptic
      mechanism of EtOH action on GABAergic transmission in the NTS as well as a
      postsynaptic mechanism in subsets of NTS neurons. EtOH application was further
      associated with a significant decrease in action potential firing in most, but
      not all, NTS neurons tested. EtOH induced a small but significant decrease in
      spontaneous excitatory postsynaptic current frequency, indicating that EtOH may
      also inhibit NTS glutamatergic signaling to some degree. Intriguingly, in vivo
      EtOH exposure (4g/kg IP) enhanced c-FOS colocalization with tyrosine hydroxylase
      via immunohistochemical methods, indicating that NTS norepinephrine neurons may
      be activated by acute EtOH exposure. Although future work is needed, the current
      data indicate that acute EtOH may enhance GABAergic signaling in local NTS
      circuits resulting in disinhibition of NTS norepinephrine neurons. Such a finding
      has important implications in understanding the role of the NTS in the
      development of alcoholism.

PMID- 28760663
TI  - Bilateral Endograft Limb Occlusion after Endovascular Aortic Repair: Predictive
      Factors of Occurrence.
AB  - BACKGROUND: Bilateral limb occlusion after endovascular aortic repair (EVAR) is
      relatively uncommon. The aim of this study was to investigate the incidence of
      bilateral endograft limb occlusion after EVAR and identify potential anatomical
      predictive factors of occurrence. METHODS: A total of 579 patients underwent
      elective EVAR for abdominal aortic aneurysm between January 2010 and December
      2015. All patients presenting with unilateral and bilateral occlusions were
      prospectively analyzed. A group of patients who underwent EVAR but did not
      present with endograft limb occlusion were matched for sex, age, and commercial
      type of endograft and were used as controls. RESULTS: Overall, 21 (3.6%) patients
      were complicated with unilateral endograft limb occlusion, whereas 8 (1.4%) of
      them presented with sequential (in different time) bilateral limb occlusion. We
      found that iliac artery angulation >=60 degrees , iliac perimeter calcification
      >=50%, and endograft oversizing in the common iliac artery of more than 15% had
      the same impact and could equally result in limb occlusion. We coded the
      variables angle, calcification, and endograft limb oversizing of the common iliac
      artery with a score from 0 to 2 as follows: (1) 0: angle <60 degrees  in both
      limbs, 1: angle >=60 degrees  in one limb, 2: angle >=60 degrees  in both limbs;
      (2) 0: calcification <50%: in both limbs, 1: calcification >= 50%: in one limb,
      2: calcification >= 50%: in both limbs; and (3) 0: endograft limb oversizing
      <15%, 1: endograft limb oversizing >=15% in one limb, 2: endograft limb
      oversizing >=15% in both limbs. A composite variable, consisting of the sum of
      scoring in variables was analyzed, with a score from 0 to 6. Our study showed
      that it was the most probable to be in the control group when score in the
      composite variable was 0-3, it was the most probable to have unilateral limb
      occlusion when score was 4-5, and finally, it was the most probable to have
      bilateral limb occlusion when score in the composite variable was equal to 6.
      CONCLUSIONS: Our study evidenced that the highest probability for bilateral limb
      occlusion occurred when implantation of a more than 15% oversized endograft in
      iliac arteries with iliac artery angulation >=60 degrees  and iliac perimeter
      calcification >=50% was present in both iliac arteries. It is therefore clear
      that limb occlusion requires the synergistic effect and interaction of bilateral
      multiple thrombogenic components in the iliac artery before it is manifested.

PMID- 28760664
TI  - Effect of 11beta-hydroxyandrostenedione on European whitefish Coregonus lavaretus
      (Linnaeus, 1758).
AB  - The goal of the present research was to evaluate the efficiency of 11beta
      hydroxyandrostenedione (OHA) applied in the diet to achieve sex reversal in the
      European whitefish (Coregonus lavaretus). At 32day post-hatching, fish were
      reared in four groups: fish fed with 10ppm of OHA (10 OHA), fish fed with 20ppm
      of OHA (20 OHA), fish fed without OHA (C) and fish fed without OHA and reared in
      the water from 20 OHA group (R). The experimental groups were conducted in
      separate recirculation systems and the first phase of the experiment lasted
      63days. For the histological analysis of the gonads, fish from all groups were
      reared without OHA treatment for an additional 91days (second phase). At the end
      of the first phase of the experiment, survival of the whitefish ranged from
      34.5+/-11.1% to 51.5+/-7.3%. The final body weight and coefficient of variation
      in the weight ranged from 5.6+/-1.2g to 6.9+/-1.5g and from 21.5 to 22.7%,
      respectively. No negative effects of OHA treatment on the growth and the survival
      of the whitefish were found. Six histological categories of the whitefish gonads
      were observed. Apart from the typical ovaries and testes, two types of the
      intersexual gonads (ovotestis and testis-ova) and two types of the sterile
      altered gonads were distinguished. No gonadal females were found among fish from
      any of OHA groups. Gonadal males constituted of 60% and 50% of the fish from 10
      OHA and 20 OHA groups, respectively. Intersexes were observed in all groups with
      the highest proportion found among fish from R variant. Rate of sterile
      individuals in 10 OHA and 20 OHA groups was 17% and 30%, respectively. The
      proportion of fish with normal testes to fish with other types of gonad varied
      from 0.43:1 to 1.5:1 with the higher ratio observed in both OHA groups. Lack of
      the females among fish from OHA groups suggested OHA affected growth and
      development of ovaries in the whitefish. However, a high percentage of the
      sterile fish in both OHA treated groups indicated application of lower doses of
      OHA for masculinization of the whitefish in the further research.

PMID- 28760665
TI  - Metritis vaccination in Holstein dairy heifers using a herd-specific multivalent
      vaccine - Effects on uterine health and fertility in first lactation.
AB  - In cattle, acute puerperal metritis (APM) compromises animal welfare and has an
      economic impact to the farmer because of the detrimental effects on reproductive
      performance, milk production, and survivability. The aim of this randomized
      clinical study was to investigate the effects of a prepartum immunization using a
      herd-specific multivalent vaccine on incidence of APM, prevalence of clinical
      endometritis (CE), and selected measures of reproductive performance in
      primiparous Holstein cows. Pregnant nulliparous cows (230+/-4days of gestation)
      assigned to the vaccinated group (VG; n=142) received subcutaneously 5.0mL of a
      multivalent herd-specific vaccine containing inactivated whole bacterial cells of
      Trueperella pyogenes, Escherichia coli, Streptococcus uberis, Bacteroides
      species, and Peptostreptococcus species obtained from uterine swabs of
      primiparous cows suffering from APM at the time of enrolment and three weeks
      later. Heifers allocated to the control group (Co; n=144) remained unvaccinated.
      Rectal temperature in the first 10days in milk (DIM) did not differ between
      treatments, and no interaction between treatment and day was observed
      (interaction treatment*day: p=0.623). Incidence of APM (VG, 46.0%, Co, 48.9%,
      p=0.588), number of antibiotic doses per cow to treat APM (VG, 0.63+/-0.81, Co,
      0.64+/-0.75, p=0.496), prevalence of CE at 35 DIM (VG, 24.6%, Co, 19.3%,
      p=0.350), first service pregnancy per artificial insemination (VG, 40.3%, Co,
      45.5%, p=0.541), number of inseminations until 150 DIM (VG, 2.0+/-1.4, Co, 1.9+/
      1.3, p=0.749), interval from calving to first service (median days, VG, 52, Co,
      52, p=0.915), and interval from calving to pregnancy (median days, VG, 90, Co,
      83, p=0.419) did not differ between VG and Co. Treatment did not affect activity
      of aspartate aminotransferase (AST) and creatine kinase (CK) or concentrations of
      beta-hydroxybutyrate (BHB) and haptoglobin in serum samples collected at 5 DIM.
      Furthermore, treatment did not influence yields of milk, fat or protein in the
      first 100 DIM. Moreover, no signs that vaccination provided an attenuation of
      severity of the APM cases were detected as the course of rectal body temperature
      and values of AST, CK, BHB, and haptoglobin were not influenced by treatment
      within the group of cows with diagnosed APM. Use of this herd-specific
      multivalent vaccine designed to reduce metritis was not efficacious at reducing
      the risk of uterine disease or influencing production and reproduction in dairy
      cows.

PMID- 28760666
TI  - Performance evaluation of the new fully automated urine particle analyser UF-5000
      compared to the reference method of the Fuchs-Rosenthal chamber.
AB  - BACKGROUND: UF-5000 is the new fully automated urine particle analyser. We
      validated its performance. METHODS: 736 urines were analysed and results were
      compared by two pathologists on uncentrifuged samples, using Fuchs-Rosenthal
      chamber. RESULTS: AUC of ROC curve ranged between 0.86 and 0.99. Sensitivity was
      >0.90 for all the elements and similar for RBC and yeasts. Specificity ranged
      between 0.74 and 0.89 for total cast, epithelial/non-squamous/renal-tubular cells
      and RBC. For all the other parameters specificity was >0.90. Comparison with
      Fuchs-Rosenthal chamber was very good for all the parameters; r ranged between
      0.52 and 0.99 except for pathological cast because of the lack of the
      pathological samples in medium and higher ranges. Linearity performance (R2) was
      1.00, 1.00 and 0.99 respectively for RBC, WBC and epithelial cells (EC). No carry
      over was observed. The within-run imprecision was 25.42%,13.81%,1.36% for RBC;
      37.50%,10.16%,1.41% for WBC and 35.25%, 17.85%,6.30% for EC at low, near the cut
      off level and high concentrations, respectively. The between-run imprecision was
      6.90%,1.60% for RBC, 4.10%,1.90% for WBC and 7.60%,7.30% for EC, using low and
      high positive quality controls, respectively. CONCLUSION: UF-5000 is an analyser
      of great interest to detect urine particle related to pathological process of
      kidney and urinary tract.

PMID- 28760667
TI  - Cell adhesion molecules expression pattern indicates that somatic cells arbitrate
      gonadal sex of differentiating bipotential fetal mouse gonad.
AB  - Unlike other organ anlagens, the primordial gonad is sexually bipotential in all
      animals. In mouse, the bipotential gonad differentiates into testis or ovary
      depending on the genetic sex (XY or XX) of the fetus. During gonad development
      cells segregate, depending on genetic sex, into distinct compartments: testis
      cords and interstitium form in XY gonad, and germ cell cysts and stroma in XX
      gonad. However, our knowledge of mechanisms governing gonadal sex differentiation
      remains very vague. Because it is known that adhesion molecules (CAMs) play a key
      role in organogenesis, we suspected that diversified expression of CAMs should
      also play a crucial role in gonad development. Using microarray analysis we
      identified 129 CAMs and factors regulating cell adhesion during sexual
      differentiation of mouse gonad. To identify genes expressed differentially in
      three cell lines in XY and XX gonads: i) supporting (Sertoli or follicular
      cells), ii) interstitial or stromal cells, and iii) germ cells, we used
      transgenic mice expressing EGFP reporter gene and FACS cell sorting. Although a
      large number of CAMs expressed ubiquitously, expression of certain genes was cell
      line- and genetic sex-specific. The sets of CAMs differentially expressed in
      supporting versus interstitial/stromal cells may be responsible for segregation
      of these two cell lines during gonadal development. There was also a significant
      difference in CAMs expression pattern between XY supporting (Sertoli) and XX
      supporting (follicular) cells but not between XY and XX germ cells. This
      indicates that differential CAMs expression pattern in the somatic cells but not
      in the germ line arbitrates structural organization of gonadal anlagen into
      testis or ovary.

PMID- 28760670
TI  - Standardization of 8-color flow cytometry across different flow cytometer
      instruments: A feasibility study in clinical laboratories in Switzerland.
AB  - The EuroFlow Consortium developed a fully standardized flow cytometric approach
      from instrument settings, through antibody panel, reagents and sample preparation
      protocols, to data acquisition and analysis. The Swiss Cytometry Society (SCS)
      promoted a study to evaluate the feasibility of using such standardized
      measurements of 8-color data across two different flow cytometry platforms -
      Becton Dickinson (BD) FACSCanto II and Beckman Coulter (BC) Navios, aiming at
      increasing reproducibility and inter-laboratory comparability of immunophenotypic
      data in clinical laboratories in Switzerland. The study was performed in two
      phases, i.e. a learning phase (round 1) and an analytical phase (rounds 2 and 3)
      consisting of a total of three rounds. Overall, 10 laboratories using BD
      FACSCanto II (n=6) or BC Navios (n=4) flow cytometers participated. Each
      laboratory measured peripheral blood samples from healthy donors stained with a
      uniform antibody panel of reagents - EuroFlow Lymphoid Screening Tube (LST) -
      applying the EuroFlow standardized protocols for instrument setup and sample
      preparation (www.EuroFlow.org). All data files were analyzed centrally and median
      fluorescence intensity (MedFI) values for individual markers on defined
      lymphocyte subsets were recorded; variability from reference MedFI values was
      assessed using performance scores. Data troubleshooting and discussion of the
      results with the participants followed after each round at SCS meetings. The
      results of the learning phase demonstrated that standardized instrument setup and
      data acquisition are feasible in routine clinical laboratories without previous
      experience with EuroFlow. During the analytical phase, highly comparable data
      were obtained at the different laboratories using either BD FACSCanto II or BC
      Navios. The coefficient of variation of MedFI for 7 of 11 markers performed
      repeatedly below 30%. In the last study round, 89% of participants scored over
      90% MedFI values within the acceptance criteria (P-score), in line with the
      results of the EuroFlow quality assessment rounds performed by the EuroFlow
      expert laboratories(Kalina et al., 2015). Central analysis of data allowed
      identification of deviations from the standardized procedures and technical
      issues (e.g. failure to perform correct instrument setup and improper
      compensation). In summary, here we show that inter-laboratory cross-platform
      standardization of 8-color flow cytometric measurements in clinical laboratories
      is feasible and allows for fully comparable MedFI results across BD FACSCanto II
      and BC Navios instruments. However, adherence to standardized protocols is
      crucial. Thus, training of the laboratory personnel in the EuroFlow standardized
      procedures is highly recommended to prevent errors in instrument setup and sample
      preparation.

PMID- 28760669
TI  - An immunoproteomic approach revealed antigenic proteins enhancing serodiagnosis
      performance of bird fancier's lung.
AB  - BACKGROUND: Bird fancier's lung (BFL) caused by repeated inhalation of avian
      proteins is the most common form of hypersensitivity pneumonitis. However, the
      exact identification of proteins involved is unknown, and serological test use
      for diagnosis need to be standardized. The objectives of this study were (i) to
      identify antigenic proteins from pigeon droppings (ii) to provide information
      about their location in avian matrices and (iii) to produce them in recombinant
      proteins to evaluate their diagnostic performances. METHOD: Antigenic proteins of
      pigeon dropping extracts were investigated using 2-dimensional immunoblotting
      with sera from patients with BFL, asymptomatic exposed controls and healthy
      volunteers. We investigated the origin of these antigenic proteins by analyzing
      droppings, blooms and sera using a shotgun proteomic analysis. BFL-associated
      proteins were produced as recombinant antigens in E. coli and were assessed in
      ELISA with sera from patients (n=25) and subject exposed controls (n=30). These
      diagnostic performances were compared with those obtained by precipitin
      techniques (agar gel double diffusion, immunoelectrophoresis). RESULTS: We
      identified 14 antigenic proteins mainly located in droppings and blooms. These
      proteins were involved in either the digestive or immune systems of pigeons.
      Using the recombinant BFL-associated proteins: Immunoglobulin lambda-like
      polypeptide-1 (IGLL1: sensitivity: 76%; specificity: 100%; AUC: 0.93) and
      Proproteinase E (ProE: sensitivity: 84%; specificity: 80%; AUC: 0.85), the ELISA
      test showed better performance than precipitin assays with pigeon dropping
      extracts (sensitivity: 60%; specificity: 93.3%; AUC: 0.76). CONCLUSION: IGLL1 and
      ProE were identified as the biomarkers of the disease. The use of these highly
      standardized antigens discriminates BFL cases from exposed subjects in
      serological assays. The results of this study offer new possibilities for the
      serological diagnosis of the disease. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov: Identifier NCT03056404.

PMID- 28760668
TI  - RIG-I Activation Protects and Rescues from Lethal Influenza Virus Infection and
      Bacterial Superinfection.
AB  - Influenza A virus infection causes substantial morbidity and mortality in
      seasonal epidemic outbreaks, and more efficient treatments are urgently needed.
      Innate immune sensing of viral nucleic acids stimulates antiviral immunity,
      including cell-autonomous antiviral defense mechanisms that restrict viral
      replication. RNA oligonucleotide ligands that potently activate the cytoplasmic
      helicase retinoic-acid-inducible gene I (RIG-I) are promising candidates for the
      development of new antiviral therapies. Here, we demonstrate in an Mx1-expressing
      mouse model of influenza A virus infection that a single intravenous injection of
      low-dose RIG-I ligand 5'-triphosphate RNA (3pRNA) completely protected mice from
      a lethal challenge with influenza A virus for at least 7 days. Furthermore,
      systemic administration of 3pRNA rescued mice with pre-established fulminant
      influenza infection and prevented the fatal effects of a streptococcal
      superinfection. Type I interferon, but not interferon-lambda, was required for
      the therapeutic effect. Our results suggest that the use of RIG-I activating
      oligonucleotide ligands has the clinical potential to confine influenza epidemics
      when a strain-specific vaccine is not yet available and to reduce lethality of
      influenza in severely infected patients.

PMID- 28760672
TI  - Electrochemical detection of interaction between capsaicin and nucleic acids in
      comparison to agarose gel electrophoresis.
AB  - In this study, the biomolecular interaction occurred between nucleic acids and
      Capsaicin (CPS), the active compound in chilli peppers, which has been reported
      to have anti-carcinogenic properties, was investigated for the first time herein
      using disposable electrochemical biosensor. It is aimed to perform the surface
      confined interaction between CPS and different types of nucleic acids and under
      this aim, the experimental conditions were optimized; such as, the concentration
      of CPS and DNA, DNA immobilization time and interaction time etc. The detection
      limit of DNA was estimated based on guanine oxidation signal in the linear
      concentration range of DNA from 1 to 5 MUg/mL, and it was found to be 0.62
      MUg/mL. The effect of time-dependent manner from 1 min to 30 min on the
      interaction of CPS with nucleic acids was explored upon to the changes at guanine
      signal coming from double stranded DNA and cDNA as well as PCR samples. The
      interaction of CPS with double stranded DNA was also determined by agarose gel
      electrophoresis.

PMID- 28760671
TI  - Application of phospho-CyTOF to characterize immune activation in patients with
      sickle cell disease in an ex vivo model of thrombosis.
AB  - Sickle cell disease (SCD) is a genetic disease caused by mutations in the beta
      globin gene, and inflammation plays a key role in driving many aspects of disease
      pathology. Early immune activation is believed to be associated with hemodynamic
      stresses and thrombus formation as cells traffic through blood vessels. We
      applied an extracorporeal perfusion system to model these effects ex vivo, and
      combined this with a phospho-CyTOF workflow to comprehensively evaluate single
      cell signatures of early activation across all major circulating immune subsets.
      These approaches showed immune activation following passage through the perfusion
      chamber, most notably in monocytes, which exhibited platelet aggregation and
      significantly elevated expression of multiple phospho-proteins. Overall, these
      studies outline a robust and broadly applicable workflow to leverage phospho
      CyTOF to characterize immune activation in response to ex vivo or in vivo
      perturbations and may facilitate identification of novel therapeutic targets in
      SCD and other inflammatory diseases.

PMID- 28760673
TI  - Isolation of mouse chromaffin secretory vesicles and their division into 12
      fractions.
AB  - The study of chromaffin secretory vesicles (SVs) has contributed immensely to our
      understanding of exocytosis. These organelles, also called chromaffin granules,
      are a specific type of large dense secretory vesicle found in many endocrine
      cells and neurons. Traditionally, they have been isolated from bovine adrenal
      glands due to the large number of SVs that can be obtained from this tissue.
      However, technical advances now make it possible to obtain very pure preparations
      of SVs from mice, which is particular interesting for functional studies given
      the availability of different genetically modified strains of mice. Despite the
      small size of the mouse adrenal medulla (400-500 MUm and less than 2 mg in
      weight), we have successfully carried out functional studies on SVs isolated from
      WT and knockout mice. As such, we present here our method to purify crude
      vesicles and to fractionate mouse chromaffin SVs, along with examples of their
      functional characterization.

PMID- 28760674
TI  - Electrophysiological assessment in structural heart disease: Stimulating thoughts
      on thoughtful stimulation.

PMID- 28760675
TI  - Alkaline hydrolysis to increase the selectivity of colorimetric determination of
      polysorbate.
AB  - Here, we describe a straightforward sample pretreatment step for the colorimetric
      cobaltthiocyanate determination of polysorbate, which circumvents the assay's
      shortcomings due to interference of protein and does not require complex
      instrumentation. Protein-containing test samples are hydrolyzed with strong
      alkali at 100  degrees C, neutralized and clarified by filtration before applying
      the colorimetric assay. The modified method performs with appropriate accuracy
      and precision, allowing specific polysorbate measurement in the presence of
      Triton X-100 during virus inactivation, determination of residual amounts of
      polysorbate in the final products and measurement of polysorbate 80 in final
      formulated products. The alkaline hydrolysis step, primarily designed to provide
      the assay's reliability in the presence of protein, also enhances its selectivity
      towards interference by the non-ionic detergent Triton X-100 and increases its
      robustness against changes in the fatty acid moiety of polysorbate as it released
      the fatty acid essentially contributing to the known heterogeneity of
      polysorbates. These results demonstrate that with sample pretreatment the handy
      colorimetric assay, not requiring complex instrumentation, can be used to measure
      polysorbate 80 concentrations in intermediates and final products of therapeutic
      protein solutions.

PMID- 28760676
TI  - Radiotherapy quality assurance and patient safety director presents:
      Accreditation survey day: Story experience & tips.

PMID- 28760678
TI  - SIRT3 inhibits Ang II-induced transdifferentiation of cardiac fibroblasts through
      beta-catenin/PPAR-gamma signaling.
AB  - AIMS: Cardiac fibrosis is an inevitable process of numerous cardiovascular
      diseases in which the transdifferentiation of cardiac fibroblasts plays a pivotal
      role. Sirtuin3 (SIRT3) has been believed to protect against cardiac fibrosis.
      However, the mechanism underlying this beneficial effect has not yet been
      elucidated. In this study, we investigated the potential mechanism of SIRT3 on
      the inhibition of fibroblast-to-myoblast transdifferentiation. MAIN METHODS:
      Cells were stimulated by angiotension II (Ang II) with SIRT3 overexpression or
      knockdown. Also, PPARgamma agonist (Pioglitazone PIO) and inhibitor (GW9662) were
      used to confirm the antifibrotic effect of PPARgamma. Western blot, qRT-PCR, CCK
      8 and immunofluorescence staining analysis were used for investigation. KEY
      FINDINGS: Our data demonstrated that overexpression of SIRT3 prevented the
      transdifferentiation of CFs while SIRT3 knockdown promoted the process.
      Simultaneously, SIRT3 overexpression increased total PPARgamma expression and
      suppressed the acetylated PPARgamma. Besides, pretreatment with PPARgamma
      agonist, pioglitazone protected CFs from transdifferentiation while PPARgamma
      inhibitor prevented the protective effect of SIRT3. In addition, we have found
      that SIRT3 upregulated the expression of PPARgamma by degeration of beta-catenin.
      SIGNIFICANCE: Our findings indicate that this newly identified SIRT3/beta
      catenin/PPAR-gamma axis will provide novel insight into the understanding of the
      mechanism of transdifferentiation of CFs to myofibroblasts.

PMID- 28760679
TI  - Amelioration of amyloid beta-induced retinal inflammatory responses by a LXR
      agonist TO901317 is associated with inhibition of the NF-kappaB signaling and
      NLRP3 inflammasome.
AB  - Amyloid beta (Abeta) is a pathogenic peptide associated with many
      neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
      The retinal inflammation in response to Abeta is implicated in the pathogenesis
      of several ocular diseases including age-related macular degeneration,
      Alzheimer's-related optic neuropathy and glaucoma. In the present study, we found
      that a single intravitreal injection of oligomeric Abeta1-40 in mouse activated
      the NLRP3 inflammasome and the NF-kappaB signaling, induced the production of
      inflammatory cytokines including TNF-alpha and IL-6. In addition, Abeta1-40
      caused retinal function impairment while no noticeable morphological changes were
      observed under light microscope. Furthermore, immunohistochemical results showed
      that Abeta1-40 enhanced the number of Iba1-positive cells in the inner retina.
      The mRNA expressions of LXRalpha and LXRbeta decreased in the neuroretina of the
      Abeta1-40-injected mice. No significant difference was found on the protein
      expressions of LXRs and ABCA1 in both neuroretina and RPE/choroid complex between
      the Abeta1-40-injected group and the control group. A synthetic LXR ligand,
      TO901317 (TO90), enhanced the expressions of LXRalpha and ABCA1 at both mRNA and
      protein levels in the Abeta1-40-injected mice, while the LXRbeta expression was
      unchanged. TO90 preserved ERG a- and b-wave amplitudes and reduced the number of
      Iba1-positive cells in the Abeta1-40-treated retina. Furthermore, TO90 down
      regulated the mRNA levels of TNF-alpha and IL-6, as well as the expressions of p
      IkappaBalpha, NLRP3, caspase-1 and IL-1beta in the Abeta1-40-injected animals. We
      suggest that activation of LXRalpha and its target gene ABCA1 exerts potent anti
      inflammatory effect on the Abeta-treated retina.

PMID- 28760680
TI  - Genetic analysis of a PER-2-producing Shewanella sp. strain harbouring a variety
      of mobile genetic elements and antibiotic resistance determinants.
AB  - The objective of this study was to investigate the molecular mechanisms
      explaining the multidrug-resistant (MDR) phenotype found in a novel clinical
      Shewanella sp. strain (Shew256) recovered from a diabetic patient. Whole-genome
      shotgun sequencing was performed using Illumina MiSeq-I and Nextera XT DNA
      library. De novo assembly was performed with SPAdes. RAST Server was used to
      predict the open-reading frames and the predictions were confirmed using BLAST.
      Further genomic analysis was carried out using average nucleotide identity (ANI),
      ACT (Artemis), OrthoMCL, ARG-ANNOT, ISfinder, PHAST, tRNAscan-SE, plasmidSPAdes,
      PlasmidFinder and MAUVE. PCR and plasmid extraction were also performed. Genomic
      analysis revealed a total of 456 predicted genes unique to Shew256 compared with
      other Shewanella genomes. Moreover, the presence of different resistance genes,
      including blaPER-2, was found. A complex class 1 integron containing the ISCR1
      gene, disrupted by two putative transposase genes, was identified. Furthermore,
      other resistance genes, a transposon containing aph(3'), insertion sequences,
      phages and non-coding RNAs were also found. In conclusion, evidence of
      acquisition of resistance genes and mobile elements that could explain the MDR
      phenotype were observed. This Shewanella sp. represents a prime example of how
      antibiotic resistance determinants can be acquired by uncommon pathogens.

PMID- 28760681
TI  - Genetic diversity of Mycobacterium tuberculosis and transmission associated with
      first-line drug resistance: a first analysis in Jalisco, Mexico.
AB  - OBJECTIVES: The objectives of this study were to analyse the frequency of gene
      mutations associated with antitubercular drug resistance in clinical samples from
      the population of Jalisco State (Mexico) and to evaluate the genetic variability
      of Mycobacterium tuberculosis and multidrug-resistant (MDR) M. tuberculosis
      strains to describe the frequency of various families. METHODS: Clinical isolates
      of M. tuberculosis obtained from Jalisco State were analysed. Isolates were
      subjected to drug susceptibility testing, and mutations were characterised by
      sequencing, followed by genotyping using spoligotyping and mycobacterial
      interspersed repetitive units-variable-number of tandem repeats (MIRU-VNTR).
      Moreover, the prevalence of mutations was analysed by phylogenetic lineages.
      RESULTS: Resistant strains were analysed by sequencing of katG, inhA and rpoB
      genes to determine the presence of mutations associated with isoniazid and
      rifampicin resistance. In MDR, monoresistant and polyresistant isolates,
      mutations were found in 17 (54.84%) of 31 strains. Spoligotyping identified six
      different strain lineages [T1 (25.40%), H3 (7.94%), MANU (4.76%), X1 (3.17%),
      EAI5 (1.59%) and LAM1 (1.59%)], with the remaining strains identified as orphans.
      In additional tree-based identification, a dendrogram of spoligotype patterns
      generated five different similarity clusters. When combining 24-loci MIRU-VNTR
      and spoligotyping approaches, the results shows that there is no cluster
      formation, indicating low transmission of the samples. CONCLUSIONS: This study
      using spoligotyping and MIRU-VNTR showed that the analysed strains were not
      related to each other since no two identical strains were found. Families with
      the highest prevalence in the study were orphans followed by T family.

PMID- 28760682
TI  - The bulbus arteriosus of the holocephalan heart: gross anatomy, histomorphology,
      pigmentation, and evolutionary significance.
AB  - This study was designed to determine whether the outflow tract of the
      holocephalan heart is composed of a myocardial conus arteriosus and a non
      myocardial bulbus arteriosus, as is the case in elasmobranchs. This is a key
      issue to verify the hypothesis that these two anatomical components existed from
      the onset of the jawed vertebrate radiation. The Holocephali are the sister group
      of the elasmobranchs, sharing with them a common, still unknown Palaeozoic
      ancestor. The sample examined herein consisted of hearts from individuals of four
      species, two of them belonging to the Chimaeridae and the other two to the
      Rhinochimaeridae. In all specimens, the cardiac outflow tract consisted of a
      conus arteriosus, with myocardium in its walls and two rows of valves at its
      luminal side, and an intrapericardial bulbus arteriosus shorter than the conus
      and devoid of valves. The bulbus, mainly composed of elastin and smooth
      musculature, was covered by the epicardium and crossed longitudinally by coronary
      artery trunks. These findings give added support to the viewpoint that the
      outflow tract of the primitive heart of the gnathostomes was not composed of a
      single component, but two, the conus and the bulbus. All rabbitfish (Chimaera
      monstrosa) examined had pigment cells over the surface of the heart. The degree
      of pigmentation, which varied widely between individuals, was particularly
      intense in the cardiac outflow tract. Pigment cells also occurred in the bulbus
      arteriosus of one of the two hearts of the straightnose rabbitfish (Rhinochimaera
      atlantica) included in the study. The cells containing pigment, presumably
      derived from the neural crest, were located in the subepicardium.

PMID- 28760683
TI  - Functional morphology of hummingbird bill tips: their function as tongue
      wringers.
AB  - Nectarivores are animals that have evolved adaptations to efficiently exploit
      floral nectar as the main source of energy in their diet. It is well known that
      hummingbirds can extract nectar with impressive speed from flowers. However,
      despite decades of study on nectar intake rates, the mechanism by which feeding
      is ultimately achieved - the release of nectar from the tongue so that it can
      pass into the throat and be ingested - has not been elucidated. By using microCT
      scanning and macro high-speed videography we scrutinized the morphology and
      function of hummingbird bill tips, looking for answers about the nectar
      offloading process. We found near the bill tip, in an area of strong lateral
      compression of internal mandibular width, that the tomia (cutting edges of the
      bill) are thinner, partially inrolled, and hold forward-directed serrations.
      Aligned with these structures, a prominent pronglike structure projects upward
      and forward from the internal mandibular keel. Distal to this mandibular prong,
      another smaller maxillary prong protrudes downwards from the keel of the palate.
      Four shallow basins occur at the base of the mandibular prong on the mandibular
      floor. Of these, two are small basins located proximally and at the sides of the
      mandibular prong. A third, slightly larger basin is positioned distally to the
      first two and directly under the maxillary prong. And the fourth basin, the
      largest, is found more proximally where the bill becomes thicker, as seen from
      the side. We documented that this group of structures is integrated into the area
      of the bill where tongue extrusion occurs, and we hypothesize that they function
      to enhance the nectar release at each lick. We suggest that this "wringer",
      operated by bill and tongue movements, helps to move nectar towards the throat.

PMID- 28760677
TI  - Optical coherence tomography angiography: A comprehensive review of current
      methods and clinical applications.
AB  - OCT has revolutionized the practice of ophthalmology over the past 10-20 years.
      Advances in OCT technology have allowed for the creation of novel OCT-based
      methods. OCT-Angiography (OCTA) is one such method that has rapidly gained
      clinical acceptance since it was approved by the FDA in late 2016. OCTA images
      are based on the variable backscattering of light from the vascular and
      neurosensory tissue in the retina. Since the intensity and phase of backscattered
      light from retinal tissue varies based on the intrinsic movement of the tissue
      (e.g. red blood cells are moving, but neurosensory tissue is static), OCTA images
      are essentially motion-contrast images. This motion-contrast imaging provides
      reliable, high resolution, and non-invasive images of the retinal vasculature in
      an efficient manner. In many cases, these images are approaching histology level
      resolution. This unprecedented resolution coupled with the simple, fast and non
      invasive imaging platform have allowed a host of basic and clinical research
      applications. OCTA demonstrates many important clinical findings including areas
      of macular telangiectasia, impaired perfusion, microaneurysms, capillary
      remodeling, some types of intraretinal fluid, and neovascularization among many
      others. More importantly, OCTA provides depth-resolved information that has never
      before been available. Correspondingly, OCTA has been used to evaluate a spectrum
      of retinal vascular diseases including diabetic retinopathy (DR), retinal venous
      occlusion (RVO), uveitis, retinal arterial occlusion, and age-related macular
      degeneration among others. In this review, we will discuss the methods used to
      create OCTA images, the practical applications of OCTA in light of invasive dye
      imaging studies (e.g. fluorescein angiography) and review clinical studies
      demonstrating the utility of OCTA for research and clinical practice.

PMID- 28760684
TI  - Bericht aus der Praxis/Practice Report: How to successfully establish PAL in
      medical education. 10 tips to succeed in PAL-based courses in undergraduate
      medical education (UGME).
AB  - This article aims to provide useful suggestions for the implementation of new
      courses with peer-assisted learning (PAL) in undergraduate medical education
      (UGME). It presents 10 key tips for needs assessment, clarification of goals and
      objectives for internal marketing, the choice of teaching formats, fund raising,
      recruiting of educators, qualification of peer tutors, the fun factor, how to
      establish a structured and longitudinal curriculum, assessment methods and
      motivation, collecting feedback and the use of its results. These 10 tips are
      linked to scientific evidence in the educational literature and elucidated by
      specific examples, based upon a major PAL project on diagnostic imaging, which
      can be transferred to other teaching topics as well. In conclusion, the described
      tips represent a helpful tool to avoid common pitfalls in the planning,
      implementation, evaluation and quality-assurance of PAL-based educational
      projects.

PMID- 28760685
TI  - [Leadership and management courses for clinicians].
AB  - OBJECTIVES: The aim of the present study was to evaluate the benefit of
      Leadership and Management Courses for clinicians, specifically which leadership
      and management contents are beneficial to their daily clinical work and whether
      these contents support their individual career. METHOD: E-mail invitations to
      participate in the study were sent to all 543 medical doctors of the University
      Hospital Hanover, Germany, who had taken part in one of the leadership and
      management courses offered between June 2005 and June 2015. The enquiry was
      carried out between June 1 and June 30, 2015. 84 e-mail addresses were no longer
      active; and so, N=459 clinicians actually received the invitation. Of these, 104
      participated (22.7%). RESULTS: The study included 59 items. Six were free text
      items, twelve items were closed questions which could be answered by choosing
      from a drop down menu, and 41 were answered on a Likert scale from 0 (not fitting
      at all) to 10 (perfect fit). Based on the items answered on a Likert scale, the
      following scales and mean values were deduced: Job Satisfaction (M=7.44);
      Leadership (M=7.77); Trust (M=7.22); Striving for Power (M=7,45); negative Affect
      (M=4,91); Target Achievement Motivation (M=8.19); Communication (M=8.30) and
      Management (M=6.48). Regression analysis showed that Job- and Team Satisfaction
      can predict to what extent the participants regard themselves as good leaders.
      The study participants defined the following topics as very important: leadership
      and management style, managerial functions, team management, human resources
      development and project management. Further topics included rhetoric skills,
      presentation techniques, as well as basic economics such as understanding balance
      sheets, profit & loss statements and contribution margin calculation. 55% of the
      course contents were described as being directly applicable to their daily
      working environment. In the clinicians' view, the ideal leader acts as a role
      model (passing on values like respect, appreciation, honesty, openness, fairness,
      sense of justice, and empathy), someone who motivates his colleagues by giving
      them a vision, structure and transparency. The participants estimated that they
      met 60% of these qualifications. 51% of the participants found the course highly
      beneficial, and 45% rated it as being beneficial. 55% said that the course
      boosted their career. 96% were willing to attend further leadership and
      management courses. 98% would recommend the course to their colleagues.
      CONCLUSION: The return rate of 22.7%, the subjective benefit of the courses
      (96%), the willingness to attend such courses (96%) and to recommend them to
      colleagues (98%) demonstrates that clinicians are highly interested in leadership
      and management topics. This may be due to the fact that these topics are not part
      of the training program for medical students or junior doctors. Our findings are
      in consistent with organisational and psychological research results showing that
      "soft" psychological factors related to leadership topics are a significant and
      crucial factor behind the success of organisations and hospitals.

PMID- 28760686
TI  - ?

PMID- 28760687
TI  - Evaluation of transporters in drug development: Current status and contemporary
      issues.
AB  - Transporters govern the access of molecules to cells or their exit from cells,
      thereby controlling the overall distribution of drugs to their intracellular site
      of action. Clinically relevant drug-drug interactions mediated by transporters
      are of increasing interest in drug development. Drug transporters, acting alone
      or in concert with drug metabolizing enzymes, can play an important role in
      modulating drug absorption, distribution, metabolism and excretion, thus
      affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug
      interaction guidance documents from regulatory agencies include various decision
      criteria that may be used to predict the need for in vivo assessment of
      transporter-mediated drug-drug interactions. Regulatory science research
      continues to assess the prediction performances of various criteria as well as to
      examine the strength and limitations of each prediction criterion to foster
      discussions related to harmonized decision criteria that may be used to
      facilitate global drug development. This review discusses the role of
      transporters in drug development with a focus on methodologies in assessing
      transporter-mediated drug-drug interactions, challenges in both in vitro and in
      vivo assessments of transporters, and emerging transporter research areas
      including biomarkers, assessment of tissue concentrations, and effect of diseases
      on transporters.

PMID- 28760688
TI  - The oligodendrocyte lineage transcription factor 2 (OLIG2) is epigenetically
      regulated in acute myeloid leukemia.
AB  - DNA methylation differences between normal tissue and cancerous tissue resulting
      in differential expression of genes are a hallmark of acute myeloid leukemia
      (AML) and can provide malignant cells with a growth advantage via silencing of
      specific genes, for example, transcription factors. Oligodendrocyte lineage
      transcription factor 2 (OLIG2) was reported to be differentially methylated and
      associated with prognosis in AML and, as reported for acute lymphoblastic
      leukemia and malignant glioma, may play a role in malignant transformation. We
      report that DNA methylation of OLIG2 is associated with decreased expression of
      mRNA in AML cell lines and patients. Moreover, in cell lines, decreased mRNA
      expression also translated into decreased OLIG2 protein expression. Treatment of
      non-expressing cell lines PL-21 and U-937 with the demethylating agent decitabine
      resulted in robust re-expression of OLIG2 on mRNA and protein levels.
      Furthermore, stable overexpression of OLIG2 in non-expressing cell lines Kasumi-1
      and U-937, using a lentiviral vector system, led to moderate growth inhibition
      after 4 days and resulted in signs of differentiation in U-937 cells.
      Interestingly, although CD34 + cells from healthy donors and 10 of 12 AML
      patients exhibited no protein expression, OLIG2 was expressed in two patients,
      both bearing the translocation t(15;17), corresponding to OLIG2 expression in NB
      4 cells, also harboring t(15;17). In conclusion, we provide first evidence that
      OLIG2 is epigenetically regulated via DNA methylation and expressed in a subset
      of AML patients. OLIG2 may exert antiproliferative activity in leukemia cell
      lines, and its potential leukemia-suppressing role in AML warrants further
      investigation.

PMID- 28760690
TI  - Validity of contents of a paediatric critical comfort scale using mixed
      methodology.
AB  - INTRODUCTION: Critical illness in paediatric patients includes acute conditions
      in a healthy child as well as exacerbations of chronic disease, and therefore
      these situations must be clinically managed in Critical Care Units. The role of
      the paediatric nurse is to ensure the comfort of these critically ill patients.
      To that end, instruments are required that correctly assess critical comfort.
      OBJECTIVE: To describe the process for validating the content of a paediatric
      critical comfort scale using mixed-method research. MATERIAL AND METHODS:
      Initially, a cross-cultural adaptation of the Comfort Behavior Scale from English
      to Spanish using the translation and back-translation method was made. After
      that, its content was evaluated using mixed method research. This second step was
      divided into a quantitative stage in which an ad hoc questionnaire was used in
      order to assess each scale's item relevance and wording and a qualitative stage
      with two meetings with health professionals, patients and a family member
      following the Delphi Method recommendations. RESULTS: All scale items obtained a
      content validity index >0.80, except physical movement in its relevance, which
      obtained 0.76. Global content scale validity was 0.87 (high). During the
      qualitative stage, items from each of the scale domains were reformulated or
      eliminated in order to make the scale more comprehensible and applicable.
      CONCLUSIONS: The use of a mixed-method research methodology during the scale
      content validity phase allows the design of a richer and more assessment
      sensitive instrument.

PMID- 28760689
TI  - Comprehensive discovery of noncoding RNAs in acute myeloid leukemia cell
      transcriptomes.
AB  - To detect diverse and novel RNA species comprehensively, we compared deep small
      RNA and RNA sequencing (RNA-seq) methods applied to a primary acute myeloid
      leukemia (AML) sample. We were able to discover previously unannotated small RNAs
      using deep sequencing of a library method using broader insert size selection. We
      analyzed the long noncoding RNA (lncRNA) landscape in AML by comparing deep
      sequencing from multiple RNA-seq library construction methods for the sample that
      we studied and then integrating RNA-seq data from 179 AML cases. This identified
      lncRNAs that are completely novel, differentially expressed, and associated with
      specific AML subtypes. Our study revealed the complexity of the noncoding RNA
      transcriptome through a combined strategy of strand-specific small RNA and total
      RNA-seq. This dataset will serve as an invaluable resource for future RNA-based
      analyses.

PMID- 28760691
TI  - Elevated cortisol awakening response associated with early life stress and
      impaired executive function in healthy adult males.
AB  - Experiencing early life stress (ELS) and subsequent dysregulation of the
      hypothalamic-pituitary-adrenal (HPA) axis may play a role in the aetiology of
      mental health disorders. However, the exact mechanisms linking HPA-axis
      dysregulation with the development of psychopathology have not been fully
      delineated. Progress in this area is hampered by the complex and often
      conflicting associations found between markers of HPA-axis function and risk
      factors for mental health disorders such as impaired executive function (EF) and
      ELS. This study investigated the association of the cortisol awakening response
      (CAR) with ELS and EF in a healthy adult male population (n=109, aged 21-63). As
      previous inconsistencies in CAR and ELS association studies may be the result of
      not considering ELS-related factors such as cumulative exposure, type of stressor
      and developmental timing of ELS, these were also investigated. The main findings
      were that the CAR was significantly elevated in individuals reporting ELS
      compared to those reporting no ELS (p=0.007) and that an elevated CAR predicted
      poorer problem solving/planning (p=0.046). Cumulative exposure, type of stressor
      and developmental timing of ELS were also found to impact significantly on the
      CAR. These results suggest that ELS is associated with chronic changes in HPA
      axis function and that these changes may be associated with impairments in
      problem solving/planning. Future work should investigate further the
      neurobiological mechanisms linking ELS, the CAR and EF and their role in
      conferring risk for the development of mental health disorders.

PMID- 28760693
TI  - The effect of rigid taping with tension on mechanical displacement of the skin
      and change in pain perception.
AB  - OBJECTIVES: To investigate the effect of rigid taping that induces mechanical
      displacement of the skin on pain perception. DESIGN: Single group experiment
      design with repeated measures. METHODS: Twenty-three active healthy volunteers
      (12 men and 11 women) participated in the study. All participants received three
      different taping procedures: no tape, taping with tension, and taping without
      tension. The order of three taping conditions was randomised. Skin displacement
      was measured during taping with tension. A pressure algometer was used to measure
      the level of pain perception once before taping, and again after each taping
      condition, in one testing session. The participants were blind to the values of
      their pressure pain threshold (PPT) during the experimental period. RESULTS: The
      mean+/-SD skin displacement in the condition of taping with tension was 2.58+/
      0.49cm. There were significant differences in PPT between taping with tension and
      taping without tension (mean difference (mean diff)+/-standard error (SE) 36.43+/
      4.22kPa, p=0.000) and no tape (mean diff+/-SE 44.31+/-3.13kPa, p=0.000). No
      significant difference in PPT between no tape and taping without tension was
      found (mean diff+/-SE 7.88+/-2.83kPa, p=0.067). CONCLUSIONS: Taping with tension
      increases the threshold of pressure pain perception. Therefore, stretch and
      compression caused by rigid taping with tension could disturb the nociceptive
      signal transmission and alter pain perception.

PMID- 28760692
TI  - Assessment and monitoring practices of Australian fitness professionals.
AB  - OBJECTIVES: Assessment and monitoring of client health and fitness is a key part
      of fitness professionals' practices. However, little is known about prevalence of
      this practice. This study describes the assessment/monitoring practices of a
      large sample of Australian fitness professionals. DESIGN: Cross-sectional.
      METHODS: In 2014, 1206 fitness professionals completed an online survey.
      Respondents reported their frequency (4 point-scale: [1] 'never' to [4] 'always')
      of assessment/monitoring of eight health and fitness constructs (e.g. body
      composition, aerobic fitness). This was classified as: (i) 'high' ('always'
      assessing/monitoring >=5 constructs); (ii) 'medium' (1-4 constructs); (iii) 'low'
      (0 constructs). Classifications are reported by demographic and fitness industry
      characteristics. The odds of being classified as a 'high assessor/monitor'
      according to social ecological correlates were examined using a multiple-factor
      logistic regression model. RESULTS: Mean age of respondents was 39.3 (+/-11.6)
      years and 71.6% were female. A total of 15.8% (95% CI: 13.7%-17.9%) were
      classified as a 'high' assessor/monitor. Constructs with the largest proportion
      of being 'always' assessed were body composition (47.7%; 95% CI: 45.0%-50.1%) and
      aerobic fitness (42.5%; 95% CI: 39.6%-45.3%). Those with the lowest proportion of
      being 'always' assessed were balance (24.0%; 95% CI: 24.7%-26.5%) and mental
      health (20.2%; 95% CI: 18.1%-29.6%). A perceived lack of client interest and
      fitness professionals not considering assessing their responsibility were
      associated with lower odds of being classified as a 'high assessor/monitor'.
      CONCLUSIONS: Most fitness professionals do not routinely assess/monitor client
      fitness and health. Key factors limiting client health assessment and monitoring
      include a perceived lack of client interest and professionals not considering
      this their role.

PMID- 28760694
TI  - Effects of tissue fixation and dehydration on tendon collagen nanostructure.
AB  - Collagen is the most prominent protein in biological tissues. Tissue fixation is
      often required for preservation or sectioning of the tissue. This may affect
      collagen nanostructure and potentially provide incorrect information when
      analyzed after fixation. We aimed to unravel the effect of 1) ethanol and
      formalin fixation and 2) 24h air-dehydration on the organization and structure of
      collagen fibers at the nano-scale using small and wide angle X-ray scattering.
      Samples were divided into 4 groups: ethanol fixed, formalin fixed, and two
      untreated sample groups. Samples were allowed to air-dehydrate in handmade Kapton
      pockets during the measurements (24h) except for one untreated group. Ethanol
      fixation affected the collagen organization and nanostructure substantially and
      during 24h of dehydration dramatic changes were evident. Formalin fixation had
      minor effects on the collagen organization but after 12h of air-dehydration the
      spatial variation increased substantially, not evident in the untreated samples.
      Generally, collagen shrinkage and loss of alignment was evident in all samples
      during 24h of dehydration but the changes were subtle in all groups except the
      ethanol fixed samples. This study shows that tissue fixation needs to be chosen
      carefully in order to preserve the features of interest in the tissue.

PMID- 28760696
TI  - Simulation training to improve 9-1-1 dispatcher identification of cardiac arrest:
      A randomized controlled trial.
AB  - BACKGROUND: The objective of this study was to test the effectiveness of
      simulation training, using actors to make mock calls, on improving Emergency
      Medical Dispatchers' (EMDs) ability to recognize the need for, and reduce the
      time to, telephone-assisted CPR (T-CPR) in simulated and real cardiac arrest 9-1
      1 calls. METHODS: We conducted a parallel prospective randomized controlled trial
      with n=157 EMDs from thirteen 9-1-1 call centers. Study participants were
      randomized within each center to intervention (i.e., completing 4 simulation
      training sessions over 12-months) or control (status quo). After the intervention
      period, performance on 9 call processing skills and 2 time-intervals were
      measured in 2 simulation assessment calls for both arms. Six of the 13 call
      centers provided recordings of real cardiac arrest calls taken by study
      participants during the study period. RESULTS: Of the N=128 EMDs who completed
      the simulation assessment, intervention participants (n=66) performed
      significantly better on 6 of 9 call processing skills and started T-CPR 23s
      faster (73 vs 91s respectively, p<0.001) compared to participants in the control
      arm (n=62). In real cardiac arrest calls, EMDs who completed 3 or 4 training
      sessions were more likely to recognize the need for T-CPR for more challenging
      cardiac arrest calls than EMDs who completed fewer than 3, including controls who
      completed no training (68% vs 53%, p=0.018). CONCLUSIONS: Simulation training
      improves call processing skills and reduces time to T-CPR in simulated call
      scenarios, and may improve the recognition of the need for T-CPR in more
      challenging real-life cardiac arrest calls. CLINICAL TRIAL REGISTRATION:
      http://www.clinicaltrials.gov Trial # NCT01972087.

PMID- 28760695
TI  - Structural and functional analyses of a TIMP and MMP in the ligament of Pinctada
      fucata.
AB  - The bivalve hinge ligament is the hard tissue that functions to open and close
      shells. The ligament contains fibrous structures consisting of aragonite crystals
      surrounded by a dense organic matrix. This organic matrix may contribute to the
      formation of fibrous aragonite crystals, but the mechanism underlying this
      formation remains unclear. In this study, we identified a novel ligament-specific
      protein, Pinctada fucata tissue inhibitor of metalloproteinase (PfTIMP), from the
      fibrous organic matrix between aragonite crystals in the ligament using the amino
      acid sequence and cDNA cloning methods. PfTIMP consists of 143 amino acid
      residues and has a molecular weight of 13,580.4. To investigate the activity of
      PfTIMP, inhibition of matrix metalloproteinase (MMP) activity was measured.
      PfTIMP strongly inhibited human MMP13 and MMP9. Eight MMP homologs were
      identified from a P. fucata genomic database by BLAST search. To identify the
      specific MMP that may contribute to ligament formation, the expression level of
      each MMP was measured in the mantle isthmus, which secretes the ligament. The
      expression of MMP54089 increased after scratching of the ligament, while the
      expressions of other MMPs did not increase after doing the same operation. To
      identify the role of MMP54089 in forming the ligament structure, double stranded
      (ds) RNA targeting MMP54089 was injected into living P. fucata to suppress the
      function of MMP54089. Scanning electron microscopic images showed disordered
      growing surfaces of the ligament in individuals injected with MMP54089-specific
      dsRNA. These results suggest that PfTIMP and MMP54089 play important roles in the
      formation of the fibrous ligament structure.

PMID- 28760697
TI  - Vision in laboratory rodents-Tools to measure it and implications for behavioral
      research.
AB  - Mice and rats are nocturnal mammals and their vision is specialized for detection
      of motion and contrast in dim light conditions. These species possess a large
      proportion of UV-sensitive cones in their retinas and the majority of their optic
      nerve axons target superior colliculus rather than visual cortex. Therefore, it
      was a widely held belief that laboratory rodents hardly utilize vision during day
      time behavior. This dogma is being questioned as accumulating evidence suggests
      that laboratory rodents are able to perform complex visual functions, such as
      perceiving subjective contours, and that declined vision may affect their
      performance in many behavioral tasks. For instance, genetic engineering may have
      unexpected consequences on vision as mouse models of Alzheimer's and Huntington's
      diseases have declined visual function. Rodent vision can be tested in numerous
      ways using operant training or reflex-based behavioral tasks, or alternatively
      using electrophysiological recordings. In this article, we will first provide a
      summary of visual system and explain its characteristics unique to rodents. Then,
      we present well-established techniques to test rodent vision, with an emphasis on
      pattern vision: visual water test, optomotor reflex test, pattern
      electroretinography and pattern visual evoked potentials. Finally, we highlight
      the importance of visual phenotyping in rodents. As the number of genetically
      engineered rodent models and volume of behavioral testing increase
      simultaneously, the possibility of visual dysfunctions needs to be addressed.
      Neglect in this matter potentially leads to crude biases in the field of
      neuroscience and beyond.

PMID- 28760698
TI  - Assessment of behavioural deficits following ischaemic stroke in the marmoset.
AB  - Stroke is a common and devastating disease worldwide. Over the last two decades,
      many therapeutic approaches to ameliorate ischaemic stroke have been promising in
      animal studies but failed when transferred to the clinical situation. One of the
      possible explanations for these failures is the widespread use of animal models
      of cerebral ischemia that do not mimic the pathology encountered in the clinic.
      Accordingly, many expert committees recommended the integration of higher order
      species such as non-human primates in pre-clinical stroke studies. The common
      marmoset (Callithrix jacchus), a small New World monkey, start to stand out in
      the neuroscience field as a good compromise between larger primates and rodents.
      In this review, we discuss the relevance of the use of the marmoset in stroke
      studies. We will focus on behavioural tests developed in this species to assess
      sensorimotor deficits and their recovery during acute and chronic stages of brain
      ischaemia. The aim of this appraisal is to provide a comprehensive overview of
      the existing approaches to induce stroke in the marmoset as well as the paradigms
      for behavioural testing in this species. The data summarized in this review
      should contribute to the improvement of future stoke studies in the marmoset and
      accordingly improve the translation of the results from bench to bed.

PMID- 28760700
TI  - Behavioral outcome measures to improve experimental stroke research.
AB  - Functional recovery after an experimental stroke can be assessed by multiple
      behavioral tests, however, there is no consensus about which test to use in long
      term stroke recovery studies or whether the tests are affected by stroke surgery,
      post-operative care or behavioral compensation due to repeated testing. This
      review describes the tests most commonly used to assess motor and sensorimotor
      function, cognition and mood in stroke animals. Although it is difficult to
      predict the direction of future research, it may be possible to prevent false
      positive results by selecting an appropriate task or a battery of tasks. It is
      also expected that the upcoming stroke recovery recommendations and the improved
      dialogue between academy, industry and healthcare professionals will further
      promote translational success.

PMID- 28760699
TI  - Modulation of the storage of social recognition memory by neurotransmitter
      systems in the insular cortex.
AB  - The insular cortex (IC) receives projections from prefrontal, entorhinal and
      cingulate cortex, olfactory bulb and basal nuclei and has reciprocal connections
      with the amygdala and entorhinal cortex. These connections suggest a possible
      involvement in memory processes; this has been borne out by data on several
      behaviors. Social recognition memory (SRM) is essential to form social groups and
      to establish hierarchies and social and affective ties. Despite its importance,
      knowledge about the brain structures and the neurotransmitter mechanisms involved
      in its processing is still scarce. Here we study the participation of NMDA
      glutamatergic, D1/D5-dopaminergic, H2-histaminergic, beta-adrenergic and 5-HT1A
      serotoninergic receptors of the IC in the consolidation of SRM. Male Wistar rats
      received intra-IC infusions of substances acting on these receptors immediately
      after the sample phase of a social discrimination task and 24h later were exposed
      to a 5-min retention test. The intra-IC infusion of antagonists of D1/D5, beta
      adrenergic or 5-HT1A receptors immediately after the sample phase impaired the
      consolidation of SRM. These effects were blocked by the concomitant intra-IC
      infusion of agonists of these receptors. Antagonists and agonists of NMDA and H2
      receptors had no effect on SRM. The results suggest that the dopaminergic D1/D5,
      beta-adrenergic and serotonergic 5-HT1A receptors in the IC, but not
      glutamatergic NMDA and the histaminergic H2 receptors, participate in the
      consolidation of SRM in the IC.

PMID- 28760701
TI  - Repeated daily administration of increasing doses of lipopolysaccharide provides
      a model of sustained inflammation-induced depressive-like behaviour in mice that
      is independent of the NLRP3 inflammasome.
AB  - Mounting preclinical evidence has implicated the NLRP3 inflammasome in depression
      related behaviours elicited by chronic stress or acute lipopolysaccharide (LPS)
      challenge. However, the relevance of acute LPS as a model of depression has been
      questioned and behavioural time-courses of its effects can be inconsistent. The
      aims of this study were (1) to develop a novel protocol for repeated daily LPS
      administration and (2) to use this model to assess the involvement of NLRP3
      inflammasome signalling in sustained inflammation-induced depressive-like
      behaviour in adult C57BL/6J mice deficient in NLRP3. Acute LPS (0.83mg/kg; i.p.)
      induced sickness behaviour evident as hypolocomotor activity. However, there was
      no significant increase in depressive-like behaviour in the forced swim test 24h
      post-administration. Interestingly, depressive-like behaviours were observed in
      the female urine sniffing test and in the sucrose preference test at 24h, but not
      48h, post-administration of acute LPS. To mimic a period of sustained
      inflammation, 3-day repeated increasing LPS doses (0.1, 0.42 and 0.83mg/kg; i.p.)
      was compared to constant LPS doses (0.83mg/kg; i.p.). Sickness behaviour was seen
      in response to increasing doses, but tolerance developed to repeated constant
      doses of LPS. Furthermore, 3-day increasing doses of LPS resulted in a
      significant increase in immobility time in the forced swim test, consistent with
      depressive-like behaviour. When NLRP3-/- mice received this 3-day increasing dose
      regimen of LPS, sickness behaviours were attenuated compared to wild-type mice.
      The behaviour in the forced swim test was not significantly altered in NLRP3-/-
      mice. We propose that this increasing repeated dosing LPS model of inflammation
      induced depressive-like behaviour may better model the sustained inflammation
      observed in depression and may provide a more translationally relevant paradigm
      to study the inflammatory mechanisms that contribute to depression.

PMID- 28760702
TI  - Impulse oscillometry, spirometry, and passive smoking in healthy children and
      adolescents.
AB  - OBJECTIVE: To identify changes in the forced and quiet breathing parameters of
      lung function in healthy children and adolescents exposed to passive smoking
      (PS). METHOD: Comparative cross-sectional study. Healthy schoolchildren aged 6 to
      14 years. We collected anthropometric data, lung function parameters using
      spirometry (forced breathing), and quiet breathing parameters using impulse
      oscillometry. The sample was divided into two groups according to exposure to PS:
      passive smoking group (PSG) and non-passive smoking group (NPSG). For the
      statistical analysis, the Shapiro-Wilk test was used to verify data normality and
      the T-test or Mann-Whitney test to compare spirometric and oscillometric
      parameters between groups (p<=0.05). MAIN FINDINGS: The study included 78
      children and adolescents, with 14 boys and 25 girls in each group. There were
      differences in the mean values for peak expiratory flow (p=0.01). There were no
      significant differences between the groups in values for z-score and lower limit
      of normal. The PSG had higher mean absolute values for reactance area (X5=0.05)
      and significant percentage of predicted values for the following impulse
      oscillometry parameters: central airway resistance (R20%, p=0.03) and for the
      indicators of presence of airway obstruction (Fres%, p=0.01; X5%=0.01% and AX%,
      p=0.01). CONCLUSION: Children and adolescents exposed to PS had lower values for
      the spirometric variables and higher values for the oscillometric variables,
      indicating changes in forced and quiet parameters of lung function compared to
      the NPSG.

PMID- 28760704
TI  - Determination of alpha-2-MRAP gene polymorphisms in nephrolithiasis patients.
AB  - BACKGROUND: The intron 5 insertion/deletion polymorphism of Alpha-2-macroglobulin
      receptor-associated protein gene (Alpha-2-MRAP) has been implicated in numerous
      diseases. The current study was designed to analyze the association of intron 5
      insertion/deletion polymorphism of Alpha-2-MRAP with nephrolithiasis patients.
      METHODS: PCR was conducted on genomic DNA of patients and control to look for
      Alpha-2-MRAP insertion/deletion polymorphism. Besides that, serum level of Alpha
      2-MRAP, oxidative stress marker myeloperoxidase, Malondialdehyde (MDA), Advanced
      oxidation protein products (AOPP), and uric acid were determined. RESULTS: The D
      and I allele frequencies were 57.50% and 42.50% in patients, 77.50% and 22.50% in
      control, individually. The result showed that II genotype was associated with
      nephrolithiasis patients group. A significant decrease was observed in serum
      Alpha-2-MRAP,myeloperoxidase and TAS,while TOS,OSI,MDA,AOPP and uric acid were
      substantially increased in II and ID when compared to DD genotype in patients
      with nephrolithiasis. CONCLUSION: Our results demonstrate for the first time that
      patients with II genotype had an increased risk of stones. Also, the results
      demonstrate that I allele of the 5 insertion/deletion polymorphism in the Alpha-2
      MRAP gene is related with an increase of oxidative stress in nephrolithiasis
      patients and may possibly impose a risk for cardiovascular diseases in patients
      with II genotype of Alpha-2-MRAP.

PMID- 28760703
TI  - Berberine-induced cardioprotection and Sirt3 modulation in doxorubicin-treated
      H9c2 cardiomyoblasts.
AB  - Doxorubicin (DOX) is one of the most widely used anti-neoplastic agents. However,
      treatment with DOX is associated with cumulative cardiotoxicity inducing
      progressive cardiomyocyte death. Sirtuin 3 (Sirt3), a mitochondrial deacetylase,
      regulates the activity of proteins involved in apoptosis, autophagy and
      metabolism. Our hypothesis is that pharmacological modulation by berberine (BER)
      pre-conditioning of Sirt3 protein levels decreases DOX-induced cardiotoxicity.
      Our results showed that DOX induces cell death in all experimental groups.
      Increase in Sirt3 content by transfection-mediated overexpression decreased DOX
      cytotoxicity, mostly by maintaining mitochondrial network integrity and reducing
      oxidative stress. p53 was upregulated by DOX, and appeared to be a direct target
      of Sirt3, suggesting that Sirt3-mediated protection against cell death could be
      related to this protein. BER pre-treatment increased Sirt3 and Sirt1 protein
      levels in the presence of DOX and inhibited DOX-induced caspase 9 and 3-like
      activation. Moreover, BER modulated autophagy in DOX-treated H9c2
      cardiomyoblasts. Interestingly, mitochondrial biogenesis markers were upregulated
      in in BER/DOX-treated cells. Sirt3 over-expression contributes to decrease DOX
      cytotoxicity on H9c2 cardiomyoblasts, while BER can be used as a modulator of
      Sirtuin function and cell quality control pathways to decrease DOX toxicity.

PMID- 28760705
TI  - Adaptation to metabolic dysfunction during aging: Making the best of a bad
      situation.
AB  - Mitochondria play a central role in energy metabolism in the process of oxidative
      phosphorylation. As importantly, they are key in several anabolic processes,
      including amino acid biosynthesis, nucleotide biosynthesis, heme biosynthesis,
      and the formation of iron-sulfur clusters. Mitochondria are also engaged in waste
      removal in the urea cycle. Their activity can lead to the formation of reactive
      oxygen species which have damaging effects in the cell. These organelles are
      dynamic, undergoing cycles of fission and fusion which can be coupled to their
      removal by mitophagy. In addition to these widely recognized processes,
      mitochondria communicate with other subcellular compartments. Various components
      of mitochondrial complexes are encoded by either the nuclear or the mitochondrial
      genome necessitating coordination between these two organelles. This article
      reviews another form of communication between the mitochondria and the nucleus,
      in which the dysfunction of the former triggers changes in the expression of
      nuclear genes to compensate for it. The most extensively studied of these
      signaling pathways is the retrograde response whose effectors and downstream
      targets have been characterized. This response extends yeast replicative lifespan
      by adapting the organism to the mitochondrial dysfunction. Similar responses have
      been found in several other organisms, including mammals. Declining health and
      function during human aging incurs energetic costs. This compensation plays out
      differently in males and females, and variation in nuclear genes whose products
      affect mitochondrial function influences the outcome. Thus, the theme of
      mitochondria-nucleus communication as an adaptive response during aging appears
      very widespread.

PMID- 28760706
TI  - Impact of the PROCESS guideline on the reporting of surgical case series: A
      before and after study.
AB  - INTRODUCTION: The PROCESS guideline was developed in 2016 through expert Delphi
      consensus. It aimed to improve the quality of reporting of surgical case series.
      This study assessed the impact of the introduction of the PROCESS guideline on
      reporting for surgical case series submitted to three journals. METHODS: 20 case
      series published in the International Journal of Surgery Case Reports (IJSCR),
      the International Journal of Surgery (IJS) or the Annals of Medicine and Surgery
      (AMS) in September to December 2016, prior to the introduction of the PROCESS
      guideline (the pre-PROCESS period), were randomly identified and scored against
      the PROCESS criteria. Two authors independently scored each article a total score
      out of 29, the 'PROCESS score' (expressed as a percentage). Scores for the two
      researchers were compared and consensus was reached to achieve a final score set.
      The process was repeated for the January 2017 to April 2017 issues of the three
      journals, post PROCESS implementation (the post-PROCESS period). RESULTS: The
      mean PROCESS score was 80% (range 66-90%) for the pre-PROCESS period and 84%
      (range 72-95%) for the post-PROCESS period, a 4% relative increase [STATS]. The
      Cohen's Kappa score between researchers was 0.907 implying very substantial
      agreement. CONCLUSION: Implementation of the PROCESS guideline resulted in a 5%
      improvement in the reporting quality of surgical case series published in three
      journals. Further research is needed to identify and successfully navigate
      existing barriers to greater compliance. Authors, reviewers and editors should
      adhere to the guidelines to boost reporting quality. Journals should develop
      their policies and guide for authors to incorporate the guideline and mandate
      compliance.

PMID- 28760707
TI  - Does tumor size have its prognostic role in colorectal cancer? Re-evaluating its
      value in colorectal adenocarcinoma with different macroscopic growth pattern.
AB  - BACKGROUND: Few previous studies have taken the growth pattern into consideration
      when analyzing the prognostic value of tumor size in colorectal cancer (CRC).
      OBJECTIVE: We sought to reveal the prognostic role of tumor size in different
      macroscopic growth patterns of CRC. MATERIALS AND METHODS: Using Cancer Center
      datasets, we identified 4057 cases with colorectal adenocarcinoma treated with
      curative resection. Macroscopic growth patterns of tumors were classified into
      three types: infiltrative, ulcerative and expansive types based on tumor gross
      appearance. Univariate and multivariate Cox regression analyses were performed to
      evaluate the prognostic factors for overall survival (OS) and disease-free
      survival (DFS). RESULTS: In whole cohort, tumor size was an independent factor
      for OS (HR 1.10, 95%CI 1.04-1.16, p < 0.001). Subgroup analysis based on
      macroscopic growth pattern suggested that tumor size was an independent factor
      for OS both in the infiltrative (HR 1.37, 95%CI 1.12-1.66, p = 0.002) group and
      ulcerative group (HR 1.08, 95%CI 1.00-1.16, p = 0.044) and tumor size (HR 1.22,
      95%CI 1.06-1.40, p = 0.004) was found as an independent factor for DFS only in
      infiltrative group. CONCLUSIONS: Tumor size is an independent factor for OS and
      DFS in patients with colorectal adenocarcinoma of infiltrative type, while only
      for OS in patients of ulcerative type.

PMID- 28760708
TI  - Experimental design and modelling approach to evaluate efficacy of beta
      lactam/beta-lactamase inhibitor combinations.
AB  - BACKGROUND: A beta-lactamase inhibitor (BLI) confers susceptibility of beta
      lactamase-expressing multidrug resistant (MDR) organisms to the partnering beta
      lactam (BL). AIMS: To discuss the experimental design and modelling strategies
      for two-drug combinations, using ceftazidime- and aztreonam-avibactam
      combinations, as examples. SOURCES: The information came from several
      publications on avibactam in vitro time-kill studies and corresponding
      pharmacodynamic models. CONTENT: The experimental design to optimally gather
      crucial information from constant-concentration time-kill studies is to use an
      agile matrix of two-drug concentration combinations that cover 0.25- to 4-fold BL
      minimum inhibitory concentration (MIC) relative to the BLI concentrations to be
      tested against the particular isolate. This shifting agile design can save
      substantial costs and resources, without sacrificing crucial information needed
      for model development. The complex synergistic BL/BLI interaction is
      quantitatively explored using a semi-mechanistic pharmacokinetic-pharmacodynamic
      (PK/PD) mathematical model that accounts for antimicrobial activities in the
      combination, bacteria-mediated BL degradation and inhibition of BL degradation by
      BLI. A predictive mathematical formulation for the two-drug killing effects
      preserves the correlation between the model-derived EC50 of BL and the BL MIC.
      The predictive value of PK/PD model is evaluated against external data that were
      not used for model development, including but not limited to in vitro hollow
      fibre and in vivo murine infection models. IMPLICATIONS: As a framework for
      translational predictions, the goal of this modelling strategy is to
      significantly decrease the decision-making time by running clinical trial
      simulations with MIC-substituted EC50 function for isolates of comparable
      susceptibility through established correlation between BL MIC and EC50 values.

PMID- 28760709
TI  - Antimicrobial susceptibility testing of Kingella kingae with broth microdilution
      and disk diffusion using EUCAST recommended media.
AB  - OBJECTIVES: Increasing use of improved culture techniques and sensitive nucleic
      acid amplification assays have resulted in recognition of Kingella kingae as an
      important cause of invasive infections in young children, especially in septic
      arthritis, osteomyelitis, bacteraemia, and endocarditis. In 2016, EUCAST
      established clinical MIC breakpoints for K. kingae (published in EUCAST Clinical
      Breakpoint Tables v 7.0, 2017). The present study was carried out to produce MIC
      zone diameter correlations for K. kingae on an international collection of
      isolates, with the aim of suggesting zone diameter breakpoints corresponding to
      the clinical MIC breakpoints. METHODS: Antimicrobial susceptibility testing was
      performed for 18 clinically relevant agents on a collection of 159 clinical
      isolates of K. kingae. Broth microdilution MIC determination and disk diffusion
      were performed according to EUCAST recommendations for fastidious organisms.
      RESULTS: The correlation between MICs and zone diameters was good for all agents
      with EUCAST breakpoints for K. kingae. beta-lactamase was detected in 41 isolates
      (26%) and these isolates were resistant to aminopenicillins. These isolates were
      also resistant to trimethoprim-sulfamethoxazole. Resistance to tetracyclines was
      detected in 8% of all isolates. All resistant isolates were correctly categorized
      for these agents with the proposed zone diameter breakpoints. One isolate,
      resistant to erythromycin but susceptible to other macrolides, was categorized as
      susceptible with erythromycin disk diffusion. No resistance was detected for the
      cephalosporins, carbapenems, and fluoroquinolones tested. CONCLUSION: Based on
      the results in this study, zone diameter breakpoints for K. kingae calibrated to
      EUCAST clinical MIC breakpoints were proposed and approved by EUCAST.

PMID- 28760710
TI  - The impact of preoperative bacteriuria on the risk of periprosthetic joint
      infection after primary knee or hip replacement: a retrospective study with a 1
      year follow up.
AB  - OBJECTIVES: Patients who undergo elective joint replacement are traditionally
      screened and treated for preoperative bacteriuria to prevent periprosthetic joint
      infection (PJI). More recently, this practice has been questioned. The purpose of
      this study was to determine whether preoperative bacteriuria is associated with
      an increased risk of PJI. METHODS: Patients who had undergone a primary hip or
      knee replacement in a tertiary care hospital between September 2002 and December
      2013 were identified from the hospital database (23 171 joint replacements, 10
      200 hips, and 12 971 knees). The results of urine cultures taken within 90 days
      before the operation were obtained. Patients with subsequent PJI or superficial
      wound infection in a 1-year follow-up period were identified based on prospective
      infection surveillance. The association between bacteriuria and PJI was examined
      using a multivariable logistic regression model that included information on the
      operated joint, age, gender and the patients' chronic diseases. RESULTS: The
      incidence of PJI was 0.68% (n = 158). Preoperative bacteriuria was not associated
      with an increased risk of PJI either in the univariate (0.51% versus 0.71%, OR
      0.72, 95% CI 0.34-1.54) or in the multivariable (OR 0.82, 95% CI 0.38-1.77)
      analysis. There were no cases where PJI was caused by a pathogen identified in
      the preoperative urine culture. Results were similar for superficial infections.
      CONCLUSIONS: There was no association between preoperative bacteriuria and
      postoperative surgical site infection. Based on these results, it seems that the
      preoperative screening and treatment of asymptomatic bacteriuria is not required.

PMID- 28760711
TI  - Incidental finding observed on a blood smear.

PMID- 28760712
TI  - Glucose impairs aspirin inhibition in platelets through a NAD(P)H oxidase
      signaling pathway.
AB  - Hyperglycemia has been suggested to play a role in the increased platelet
      resistance to antiplatelet therapy in patients with diabetes mellitus. Exposure
      to high glucose impairs platelet inhibition by aspirin. It has been found that
      antioxidant agents reduce the effect of glucose, confirming the involvement of
      reactive oxygen species (ROS) in the effect of glucose. The aim of the study was
      to examine the mechanism of ROS increase by high glucose in aspirin-treated
      platelets. Platelet aggregation was measured by the optical method, and the
      production of ROS was detected using luminol-dependent horseradish peroxidase
      enhanced chemiluminescence. We found that glucose did not affect ADP-induced
      platelet aggregation. However, it reduced the effect of aspirin on platelet
      aggregation, which was accompanied by an increase in ROS generation. The
      inhibition of NAD(P)H oxidase (NOX) prevented the glucose effect and ROS
      generation. The same result was recorded after the inhibition of p38 mitogen
      activated protein kinases (p38 MAPK), phospholipase A2 (PLA2) or 12-lipoxygenase
      (12-LOX). The inhibition of TxA2 receptor did not decrease the effect of glucose
      indicating that the effect was not caused by activation of TxA2 receptors.

PMID- 28760713
TI  - Histopathological comparison of bone healing effects of endonasal and
      percutaneous lateral osteotomy methods in rabbit rhinoplasty model.
AB  - INTRODUCTION: Lateral osteotomy is mainly performed either endonasally or
      percutaneously in rhinoplasty which is a frequently performed operation for the
      correction of nasal deformities. Both techniques have both advantages and
      disadvantages relative to each other. OBJECTIVE: The aim of this study was to
      compare the histopathological effects of endonasal and percutaneous osteotomy
      techniques performed in rhinoplasty on bone healing and nasal stability in an
      experimental animal model. METHODS: Eight one year-old New Zealand white rabbits
      were included. Xylazine hydrocloride and intramuscular ketamine anesthesia were
      administered to the rabbits. Endonasal osteotomy (8 bones) was performed in Group
      1 (n=4), and percutaneous osteotomy (8 bones) in Group 2 (n=4). One month later
      the rabbits were sacrificed. Bone healing of the rabbits was staged according to
      the bone healing score of Huddleston et al. In both groups, nasal bone integrity
      was assessed subjectively. RESULTS: In the percutaneous osteotomy group, Grade 1
      bone healing was observed in two samples (25%), Grade 2 bone healing in two
      samples (25%), Grade 3 bone healing in four samples (50%). In the endonasal
      osteotomy group, Grade 1 bone healing was observed in 6 samples (75%) and Grade 2
      bone healing was observed in 2 samples (25%). In the percutaneous group, fibrous
      tissue was observed in 2, predominantly fibrous tissue and a lesser amount of
      cartilage was observed in 2 and an equal amount of fibrous tissue and cartilage
      was observed in 4 samples. In the endonasal group, fibrous tissue was observed in
      6 samples, and predominantly fibrous tissue with a lesser amount of cartilage was
      observed in 2 samples. In both groups, when manual force was applied to the nasal
      bones, subjectively the same resistance was observed. CONCLUSION: Percutaneous
      lateral osteotomy technique was found to result in less bone and periost trauma
      and better bone healing compared to the endonasal osteotomy technique.

PMID- 28760714
TI  - Giant fronto-ethmoidal osteoma - selection of an optimal surgical procedure.
AB  - INTRODUCTION: Osteomas of the paranasal sinuses are benign bone tumours that
      produce clinical signs depending on their size and location. In most reported
      cases large tumours are excised by an external approach or in conjunction with an
      endoscopic technique. Endoscopic treatment of such tumours is a huge challenge
      for the operator. OBJECTIVE: Determine the optimal surgical approach by analysing
      giant osteomas of the frontal and ethmoidal sinuses in the literature. METHODS:
      Group of 37 osteomas obtained from the literature review. A group of osteomas
      removed only by endoscopy was compared with a group in which an external approach
      (lateral rhynotomy or craniotomy) or combined external and endoscopic approach
      was applied. RESULTS: The authors, based on the statistical analysis of the
      literature data, have found that the average size of osteomas excised
      endoscopically and those removed by external approaches does not differ
      statistically, when the osteomas are located in the ethmoidal cells (p=0.2691)
      and the frontal sinuses (p=0.5891). CONCLUSION: The choice of surgical method
      appears to be independent of the osteoma size and the decision is likely to be
      taken based on the experience of the surgeon, available equipment and knowledge
      of different surgical techniques.

PMID- 28760716
TI  - The growth hormone signaling system: Insights into coordinating the anabolic and
      catabolic actions of growth hormone.
AB  - Although growth hormone (GH) is a multifunctional factor that coordinates various
      aspects of feeding, reproduction, osmoregulation, and immune system function,
      perhaps two of its most studied actions are the regulation of growth and
      metabolism, particularly lipid metabolism. In this review, we describe the major
      growth-promoting and lipid metabolic actions of GH and then discuss how the GH
      system regulates these actions. Numerous intrinsic and extrinsic factors provide
      information about the metabolic status of the organism and influence the
      production of release of GH. The actions of GH are mediated by GH receptors
      (GHR), which are widely distributed among tissues. Teleosts possess multiple
      forms of GHRs that arose through the evolution of this group. Modulation of
      tissue responsiveness to GH is regulated by molecular and functional expression
      of GHRs, and in teleosts GHR subtypes, by various factors that reflect the
      metabolic and growth status of the organism, including nutritional state. The
      action of GH is propagated by the linkage of GHRs to several cellular effector
      systems, including JAK-STAT, ERK, PI3K-Akt, and PKC. The differential activation
      of these pathways, which is governed by nutrient status, underlies GH stimulation
      of growth or GH stimulation of lipolysis. Taken together, the multi-functional
      actions of GH are determined by the distribution and abundance of GHRs (and GHR
      subtypes in teleosts) as well as by the GHR-effector system linkages.

PMID- 28760715
TI  - Water protection after tympanostomy (Shepard) tubes does not decrease otorrhea
      incidence - retrospective cohort study.
AB  - INTRODUCTION: Myringotomy for tube insertion is the most common otologic surgery.
      Otorrhea is a frequent complication of this procedure and, to prevent it, most
      surgeons strongly recommend avoiding contact with water as this is thought to
      adversely impact on post-operative quality of life. OBJECTIVE: To understand the
      benefit of this recommendation. METHODS: Observational study - retrospective
      cohort study comparing the incidence of post-operative otorrhea and its impact on
      patients' quality of life, in two groups of patients comprising children under 10
      years of age who underwent bilateral myringotomy and tube placement for chronic
      otitis media with effusion between May 2011 and May 2012. One group received
      water protection care after surgery, the other did not. Data was collected
      through telephonic interview, after one year of follow up (one year after the
      procedure). Water exposure without protection was considered the exposure event.
      Incidence of otorrhea and perceived impact on quality of life were the outcome
      measures. Results were compared after logistic regression. RESULTS: We included
      143 children: 116 were not exposed to water without protection and 27 were
      exposed. In the not exposed group 36.2% had at least one episode of otorrhea,
      compared to 40.0% of the exposed group. Odds ratio for otorrhea on exposed was
      1.21 (95% CI 0.51-2.85, p=0.6). Negative impact on quality of life was reported
      by parents of 48.2% on the not exposed children, compared to 40.7% on the exposed
      group. This difference was not significant (p=0.5). CONCLUSION: We found that
      recommending water protection did not have beneficial effect on the incidence of
      otorrhea after myringotomy with tubes on chronic otitis media with effusion.
      However, such measures did not appear to have a negative impact on quality of
      life. This is a populational observational study with few cases (143 cases);
      these final statements would be better stated by a very large populational study
      with another large control group.

PMID- 28760717
TI  - Nanog suppresses the expression of vasa by directly regulating nlk1 in the early
      zebrafish embryo.
AB  - Nanog is a homeodomain transcription factor that is essential for maintenance of
      pluripotency and self-renewal of embryonic stem cells (ESCs). In the present
      study, we demonstrate that zebrafish Nanog (zNanog) directly binds to the
      promoter region of zebrafish nlk1 (znlk1) by ChIP-Seq analysis and that it up
      regulates the expression of znlk1 in fibroblast-like embryonic cells of Danio
      rerio (ZEM-2S cells) and in zebrafish embryos at 30% epiboly both at the mRNA and
      protein levels. In addition, compared with control (MO-C) embryos at 30% epiboly,
      the mRNA and protein expression of vasa and the numbers of vasa-positive cells
      were increased in embryos injected with zNanog morpholino (MO-zNanog). Further,
      injection of znlk1 mRNA into zNanog-depleted embryos restored the expression of
      vasa and the number of vasa-positive cells. These data indicated that zNanog up
      regulates the expression of znlk1 through directly binding to the znlk1 promoter,
      thereby suppressing the expression of vasa. Vasa is a marker gene for PGCs. Our
      results suggest that zNanog plays a role in restraint of PGC cell number through
      regulating the expression of znlk1 in the early embryonic development. The
      current results provide fundamental information to support further investigation
      regarding the regulatory mechanism of zNanog during the development of PGCs.

PMID- 28760718
TI  - Crocodylian nuclear factor kappa B.
AB  - We deduced the amino acid (aa) sequence of the nuclear factor kappa B (NFkappaB)
      protein from genomic data for the American alligator (Alligator
      mississippiensis), the estuarine crocodile (Crocodylus porosus), and the Indian
      gharial (Gavialis gangeticus). A 105kDa protein, NFkappaB1 exhibits complex post
      translational processing, multiple mechanisms of activation, and acts as
      precursor for a p50, a Rel homology transcription factor which influences the
      expression of key genes for developmental processes, apoptosis, and immune
      function. The aa sequences of the crocodylian proteins share very high identity
      with each other (97.2+/-0.7%), birds (81.0+/-1.1%, n=6), mammals (75.3+/-1.6%,
      n=4), reptiles (80.3+/-5.1%, n=2), and less identity with fish (55.5+/-5.5%, n=4)
      and one amphibian (66.1+/-0.8%). The crocodylian protein has a well-conserved Rel
      homology domain, a nuclear localization signal, and a glycine-rich region which
      facilitates proteasome-mediated generation of p50. The Rel homology domain
      contains sequences responsible for dimerization, DNA-binding, and nuclear
      translocation. In addition, seven ankyrin repeats were located, which putatively
      allow for inhibition of transcriptional regulation by mediating interaction with
      Inhibitor kappa B. Other features include a death domain, and conserved serine
      residues, near the C-terminal end, which act as potential phosphorylation sites
      for activation of the proteolytic generation of p50. Western blot analysis showed
      both the 105kDa precursor and the 50kDa mature NFkappaB were expressed in the
      alligator liver. Nuclear factor kappaB exhibited diffuse cytoplasmic distribution
      in alligator hepatocytes, and almost no cytoplasmic localization in infected
      animals. In addition, nuclear NFkappaB exhibited specific binding to the
      consensus NFkappaB promoter element.

PMID- 28760720
TI  - Profilin, a Change in the Paradigm.
AB  - Profilin is a protein that is present in all eukaryotic cells and is responsible
      for cross-reactivity between pollen, latex, and plant foods. It has been
      classically acknowledged as a minor or nearly irrelevant allergen, although
      recent data are changing this conception. The objective of this manuscript is to
      provide a comprehensive review of published data on the role of this ubiquitous
      allergen in pollen, latex, and plant food allergy. The patterns of recognition of
      this minor allergen follow a north-south gradient. Although present in all
      pollens and vegetables, profilin is significantly associated with allergy to
      grass pollen and to Cucurbitaceae fruits. Heb v 8, the latex profilin, is usually
      a marker of profilin allergy in plant food-allergic patients, although it has no
      clinical relevance in latex allergy. Sensitization to profilin jeopardizes the
      diagnosis of pollen allergy and selection of immunotherapy, and although
      component-resolved diagnosis can identify its impact, there are no tailored
      treatments available. In recent years, several new publications have shown how
      profilin should be taken into account and, under certain circumstances,
      considered a marker of severity, an allergen capable of inducing respiratory
      symptoms, and, in its natural purified form, a potential candidate for
      etiological treatment of food allergy. Current data on profilin strongly support
      the need for a shift in the previously accepted paradigm for this allergen. More
      research should be done to assess the real clinical impact of sensitization in
      specific populations and to develop therapeutic strategies.

PMID- 28760719
TI  - Ambient Coarse Particulate Matter and the Right Ventricle: The Multi-Ethnic Study
      of Atherosclerosis.
AB  - BACKGROUND: Coarse particulate matter (P10-2.5) is primarily mechanically
      generated and includes crustal material, brake and tire wear, and biological
      particles. PM10-2.5 is associated with pulmonary disease, which can lead to right
      ventricular (RV) dysfunction. Although RV characteristics have been associated
      with combustion-related pollutants, relationships with PM10-2.5 remain unknown.
      OBJECTIVES: To quantify cross-sectional associations between RV dysfunction and
      PM10-2.5 mass and components among older adults and susceptible populations.
      METHODS: We used baseline cardiac magnetic resonance images from 1,490
      participants (45-84 y old) from the Multi-Ethnic Study of Atherosclerosis and
      assigned 5-y residential concentrations of PM10-2.5 mass, copper, zinc,
      phosphorus, silicon, and endotoxin, using land-use regression models. We
      quantified associations with RV mass, end-diastolic volume, and ejection fraction
      after control for risk factors and copollutants using linear regression. We
      further examined personal susceptibility. RESULTS: We found positive associations
      of RV mass and, to a lesser extent, end diastolic volume with PM10-2.5 mass among
      susceptible populations including smokers and persons with emphysema. After
      adjustment for copollutants, an interquartile range increase in PM10-2.5 mass
      (2.2 MUg/m3) was associated with 0.5 g (95% CI: 0.0, 1.0), 0.9 g (95% CI: 0.1,
      1.7), and 1.4 g (95% CI: 0.4, 2.5) larger RV mass among former smokers, current
      smokers, and persons with emphysema, respectively. No associations were found
      with healthy individuals or with ejection fraction. CONCLUSIONS: Alterations to
      RV structure may represent a mechanism by which long-term PM10-2.5 exposure
      increases risks for adverse respiratory and cardiovascular outcomes, especially
      among certain susceptible populations. https://doi.org/10.1289/EHP658.

PMID- 28760721
TI  - Transcatheter aortic valve implantation versus redo surgery for failing surgical
      aortic bioprostheses: a multicentre propensity score analysis.
AB  - AIMS: Transcatheter aortic valve implantation for a failing surgical
      bioprosthesis (TAV-in-SAV) has become an alternative for patients at high risk
      for redo surgical aortic valve replacement (redo-SAVR). Comparisons between these
      approaches are non-existent. This study aimed to compare clinical and
      echocardiographic outcomes of patients undergoing TAV-in-SAV versus redo-SAVR
      after accounting for baseline differences by propensity score matching. METHODS
      AND RESULTS: Patients from seven centres in Europe and Canada who had undergone
      either TAV-in-SAV (n=79) or redo-SAVR (n=126) were identified. Significant
      independent predictors used for propensity scoring were age, NYHA functional
      class, number of prior cardiac surgeries, urgent procedure, pulmonary
      hypertension, and COPD grade. Using a calliper range of +/-0.05, a total of 78
      well-matched patient pairs were found. All-cause mortality was similar between
      groups at 30 days (6.4% redo-SAVR vs. 3.9% TAV-in-SAV; p=0.49) and one year
      (13.1% redo-SAVR vs. 12.3% TAV-in-SAV; p=0.80). Both groups also showed similar
      incidences of stroke (0% redo-SAVR vs. 1.3% TAV-in-SAV; p=1.0) and new pacemaker
      implantation (10.3% redo-SAVR vs. 10.3% TAV-in-SAV; p=1.0). The incidence of
      acute kidney injury requiring dialysis was numerically lower in the TAV-in-SAV
      group (11.5% redo-SAVR vs. 3.8% TAV-in-SAV; p=0.13). The TAV-in-SAV group had a
      significantly shorter median total hospital stay (12 days redo-SAVR vs. 9 days
      TAV-in-SAV; p=0.001). CONCLUSIONS: Patients with aortic bioprosthesis failure
      treated with either redo-SAVR or TAV-in-SAV have similar 30-day and one-year
      clinical outcomes.

PMID- 28760722
TI  - Optical coherence tomography assessment of newgeneration mesh-covered stents
      after carotid stenting.
AB  - AIMS: The aim of this study was to identify the findings (by optical coherence
      tomography [OCT]) after carotid artery stenting (CAS) with two different types of
      new-generation mesh-covered stent. METHODS AND RESULTS: Sixteen consecutive
      patients undergoing CAS with mesh-covered stents and highdefinition OCT image
      acquisition were enrolled in the study. Cross-sectional OCT images for the
      presence of strut malapposition (SM) and plaque prolapse (PP) were evaluated
      using a proximal or distal embolic protection device (EPD). CGuard stents were
      used in 11 patients (68.8%) and RoadSaver stents in five (31.2%). With OCT
      analysis, the incidence of SM was 20.5% for CGuard vs. 26.8% for RoadSaver,
      p=0.26, and the incidence of PP was 10.8% for CGuard vs. 20.7% for RoadSaver,
      p=0.05. No neurological complications (stroke/TIA) occurred during the procedural
      and post-procedural periods. CONCLUSIONS: The OCT findings of two different types
      of mesh-covered stent after CAS were obtained safely. Our work indicates that
      current mesh-covered carotid stents may show differences in SM and PP. The effect
      of stent design and implantation technique on OCT findings post CAS, and their
      relation to longterm clinical outcomes, require further evaluation.

PMID- 28760723
TI  - Impact of residual SYNTAX score on clinical outcomes after incomplete
      revascularisation percutaneous coronary intervention: a large single-centre
      study.
AB  - AIMS: This study aimed to assess the prognostic capacity of the residual SYNTAX
      score (rSS) in a large cohort of patients undergoing percutaneous coronary
      intervention (PCI) in clinical practice. METHODS AND RESULTS: Ten thousand three
      hundred and forty-four (10,344) consecutive patients were prospectively enrolled.
      Complete revascularisation (CR; rSS=0), reasonable incomplete revascularisation
      (RICR; 0<rSS<=8), and ICR (rSS>8) were achieved in 5,375 (51.9%), 3,401 (32.9%),
      and 1,568 (15.2%) patients, respectively. During two-year follow-up, ICR patients
      had the highest incidence of major adverse cardiovascular and cerebrovascular
      events (MACCE; 20.0% vs. 13.6% vs. 8.7%, respectively; p<0.001). There was no
      difference in the incidence of all-cause death (1.2% vs. 1.0%; p=0.45), cardiac
      death (0.6% vs. 0.5%; p=0.31), and myocardial infarction (2.2% vs. 1.6%; p=0.07)
      between RICR and CR patients, while the rate of repeat revascularisation was
      significantly higher in RICR patients (9.8% vs. 5.8%; p<0.001). After
      multivariate analysis, rSS was an independent predictor of two-year cardiac
      death, myocardial infarction, revascularisation, and MACCE (p<0.05). CONCLUSIONS:
      Despite an increase in revascularisation, RICR was associated with a similar
      mortality and myocardial infarction to CR patients. rSS is a prognostic indicator
      after PCI in daily practice, and may be used to determine a reasonable level of
      revascularisation.

PMID- 28760724
TI  - Lesion preparation with cutting balloon angioplasty is associated with coronary
      aneurysm formation in polylactide bioresorbable vascular scaffold implantation.

PMID- 28760725
TI  - What Patients Can Tell Us: Topic Analysis for Social Media on Breast Cancer.
AB  - BACKGROUND: Social media dedicated to health are increasingly used by patients
      and health professionals. They are rich textual resources with content generated
      through free exchange between patients. We are proposing a method to tackle the
      problem of retrieving clinically relevant information from such social media in
      order to analyze the quality of life of patients with breast cancer. OBJECTIVE:
      Our aim was to detect the different topics discussed by patients on social media
      and to relate them to functional and symptomatic dimensions assessed in the
      internationally standardized self-administered questionnaires used in cancer
      clinical trials (European Organization for Research and Treatment of Cancer
      [EORTC] Quality of Life Questionnaire Core 30 [QLQ-C30] and breast cancer module
      [QLQ-BR23]). METHODS: First, we applied a classic text mining technique, latent
      Dirichlet allocation (LDA), to detect the different topics discussed on social
      media dealing with breast cancer. We applied the LDA model to 2 datasets composed
      of messages extracted from public Facebook groups and from a public health forum
      (cancerdusein.org, a French breast cancer forum) with relevant preprocessing.
      Second, we applied a customized Jaccard coefficient to automatically compute
      similarity distance between the topics detected with LDA and the questions in the
      self-administered questionnaires used to study quality of life. RESULTS: Among
      the 23 topics present in the self-administered questionnaires, 22 matched with
      the topics discussed by patients on social media. Interestingly, these topics
      corresponded to 95% (22/23) of the forum and 86% (20/23) of the Facebook group
      topics. These figures underline that topics related to quality of life are an
      important concern for patients. However, 5 social media topics had no
      corresponding topic in the questionnaires, which do not cover all of the
      patients' concerns. Of these 5 topics, 2 could potentially be used in the
      questionnaires, and these 2 topics corresponded to a total of 3.10% (523/16,868)
      of topics in the cancerdusein.org corpus and 4.30% (3014/70,092) of the Facebook
      corpus. CONCLUSIONS: We found a good correspondence between detected topics on
      social media and topics covered by the self-administered questionnaires, which
      substantiates the sound construction of such questionnaires. We detected new
      emerging topics from social media that can be used to complete current self
      administered questionnaires. Moreover, we confirmed that social media mining is
      an important source of information for complementary analysis of quality of life.

PMID- 28760726
TI  - Triaging Patient Complaints: Monte Carlo Cross-Validation of Six Machine Learning
      Classifiers.
AB  - BACKGROUND: Unsolicited patient complaints can be a useful service recovery tool
      for health care organizations. Some patient complaints contain information that
      may necessitate further action on the part of the health care organization and/or
      the health care professional. Current approaches depend on the manual processing
      of patient complaints, which can be costly, slow, and challenging in terms of
      scalability. OBJECTIVE: The aim of this study was to evaluate automatic patient
      triage, which can potentially improve response time and provide much-needed
      scale, thereby enhancing opportunities to encourage physicians to self-regulate.
      METHODS: We implemented a comparison of several well-known machine learning
      classifiers to detect whether a complaint was associated with a physician or
      his/her medical practice. We compared these classifiers using a real-life dataset
      containing 14,335 patient complaints associated with 768 physicians that was
      extracted from patient complaints collected by the Patient Advocacy Reporting
      System developed at Vanderbilt University and associated institutions. We
      conducted a 10-splits Monte Carlo cross-validation to validate our results.
      RESULTS: We achieved an accuracy of 82% and F-score of 81% in correctly
      classifying patient complaints with sensitivity and specificity of 0.76 and 0.87,
      respectively. CONCLUSIONS: We demonstrate that natural language processing
      methods based on modeling patient complaint text can be effective in identifying
      those patient complaints requiring physician action.

PMID- 28760727
TI  - Randomized Trial Comparing the Electronic Composite Psychosocial Screener
      YouthCHAT With a Clinician-Interview Assessment for Young People: A Study
      Protocol.
AB  - BACKGROUND: Psychosocial problems such as depression, anxiety, and substance
      abuse are common and burdensome in young people, particularly those with long
      term physical conditions such as asthma and diabetes. In New Zealand, "screening"
      for such problems is undertaken routinely only with Year 9 students in low-decile
      schools and opportunistically in pediatric settings using a nonvalidated and time
      consuming clinician-administered Home, Education/employment, Eating, Activity,
      Drugs, Sexuality, Suicide/depression, Safety (HEEADSSS) interview. The Youth
      version, Case-finding and Help Assessment Tool (YouthCHAT) is a relatively new,
      locally developed, eTablet-based composite screener for identifying similar
      psychosocial issues to HEEADSSS. Based on individually validated screening
      instruments, it is self-administered within minutes. Preliminary testing has
      revealed its acceptability to young people, but further research is required to
      expand its modules to cover all HEEADSSS domains, to evaluate its acceptability
      for young people with and without long-term physical conditions, and to compare
      its effectiveness against HEEADSSS. OBJECTIVE: Our aim is to (1) ascertain
      acceptability and utility of YouthCHAT for children with long-term physical
      illness and high school students, (2) validate three additional YouthCHAT domains
      against comparable HEEADSSS domains, and (3) compare the performance of YouthCHAT
      and HEEADSSS in the high school setting. METHODS: During the first phase of the
      study, three additional YouthCHAT domains were codesigned with high school
      students. During the second phase of the study, the updated version of YouthCHAT
      will be administered to 30 young people with long-term physical conditions, and
      to 150 high school students either before or after HEEADSSS in the form of a
      randomized trial with counter-balanced design. Primary outcomes include
      comparability between HEEADSSS and YouthCHAT in detecting psychosocial issues,
      and time to administer; acceptability of YouthCHAT as an acceptable alternative
      or companion to HEEADSSS assessment; and the utility of YouthCHAT in helping
      streamline assessment processes. RESULTS: Recruitment for the first phase of this
      project commenced in November 2016, and the phase will run from February to
      November 2017. CONCLUSIONS: If YouthCHAT is found to be acceptable to study
      participants and as effective as a HEEADSSS assessment, it could be an innovative
      and more efficient means of routine screening for common psychosocial health
      issues in young people with and without long-term physical conditions. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR)
      ACTRN12616001243404p;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371422 (Archived
      by WebCite at http://www.webcitation.org/ 6rmlEiM1L).

PMID- 28760728
TI  - Enabling Open Science for Health Research: Collaborative Informatics Environment
      for Learning on Health Outcomes (CIELO).
AB  - BACKGROUND: There is an emergent and intensive dialogue in the United States with
      regard to the accessibility, reproducibility, and rigor of health research. This
      discussion is also closely aligned with the need to identify sustainable ways to
      expand the national research enterprise and to generate actionable results that
      can be applied to improve the nation's health. The principles and practices of
      Open Science offer a promising path to address both goals by facilitating (1)
      increased transparency of data and methods, which promotes research
      reproducibility and rigor; and (2) cumulative efficiencies wherein research tools
      and the output of research are combined to accelerate the delivery of new
      knowledge in proximal domains, thereby resulting in greater productivity and a
      reduction in redundant research investments. OBJECTIVES: AcademyHealth's
      Electronic Data Methods (EDM) Forum implemented a proof-of-concept open science
      platform for health research called the Collaborative Informatics Environment for
      Learning on Health Outcomes (CIELO). METHODS: The EDM Forum conducted a user
      centered design process to elucidate important and high-level requirements for
      creating and sustaining an open science paradigm. RESULTS: By implementing CIELO
      and engaging a variety of potential users in its public beta testing, the EDM
      Forum has been able to elucidate a broad range of stakeholder needs and
      requirements related to the use of an open science platform focused on health
      research in a variety of "real world" settings. CONCLUSIONS: Our initial design
      and development experience over the course of the CIELO project has provided the
      basis for a vigorous dialogue between stakeholder community members regarding the
      capabilities that will add the greatest value to an open science platform for the
      health research community. A number of important questions around user
      incentives, sustainability, and scalability will require further community
      dialogue and agreement.

PMID- 28760729
TI  - Using Digital Technologies in Clinical HIV Research: Real-World Applications and
      Considerations for Future Work.
AB  - BACKGROUND: Digital technologies, especially if used in novel ways, provide a
      number of potential advantages to clinical research in trials related to human
      immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) and
      may greatly facilitate operations as well as data collection and analysis. These
      technologies may even allow answering questions that are not answerable with
      older technologies. However, they come with a variety of potential concerns for
      both the participants and the trial sponsors. The exact challenges and means for
      alleviation depend on the technology and on the population in which it is
      deployed, and the rapidly changing landscape of digital technologies presents a
      challenge for creating future-proof guidelines for technology application.
      OBJECTIVE: The aim of this study was to identify and summarize some common themes
      that are frequently encountered by researchers in this context and highlight
      those that should be carefully considered before making a decision to include
      these technologies in their research. METHODS: In April 2016, the Global HIV
      Vaccine Enterprise surveyed the field for research groups with recent experience
      in novel applications of digital technologies in HIV clinical research and
      convened these groups for a 1-day meeting. Real-world uses of various
      technologies were presented and discussed by 46 attendees, most of whom were
      researchers involved in the design and conduct of clinical trials of biomedical
      HIV prevention and treatment approaches. After the meeting, a small group of
      organizers reviewed the presentations and feedback obtained during the meeting
      and categorized various lessons-learned to identify common themes. A group of 9
      experts developed a draft summary of the findings that was circulated via email
      to all 46 attendees for review. Taking into account the feedback received, the
      group finalized the considerations that are presented here. RESULTS: Meeting
      presenters and attendees discussed the many successful applications of digital
      technologies to improve research outcomes, such as those for recruitment and
      enrollment, participant identification, informed consent, data collection, data
      quality, and protocol or treatment adherence. These discussions also revealed
      unintended consequence of technology usage, including risks to study participants
      and risks to study integrity. CONCLUSIONS: Key lessons learned from these
      discussions included the need to thoroughly evaluate systems to be used, the idea
      that early success may not be sustained throughout the study, that some failures
      will occur, and considerations for study-provided devices. Additionally, taking
      these key lessons into account, the group generated recommendations on how to
      move forward with the use of technology in HIV vaccine and biomedical prevention
      trials.

PMID- 28760730
TI  - Designing Serious Computer Games for People With Moderate and Advanced Dementia:
      Interdisciplinary Theory-Driven Pilot Study.
AB  - BACKGROUND: The field of serious games for people with dementia (PwD) is mostly
      driven by game-design principals typically applied to games created by and for
      younger individuals. Little has been done developing serious games to help PwD
      maintain cognition and to support functionality. OBJECTIVES: We aimed to create a
      theory-based serious game for PwD, with input from a multi-disciplinary team
      familiar with aging, dementia, and gaming theory, as well as direct input from
      end users (the iterative process). Targeting enhanced self-efficacy in daily
      activities, the goal was to generate a game that is acceptable, accessible and
      engaging for PwD. METHODS: The theory-driven game development was based on the
      following learning theories: learning in context, errorless learning, building on
      capacities, and acknowledging biological changes-all with the aim to boost self
      efficacy. The iterative participatory process was used for game screen
      development with input of 34 PwD and 14 healthy community dwelling older adults,
      aged over 65 years. Development of game screens was informed by the bio
      psychological aging related disabilities (ie, motor, visual, and perception) as
      well as remaining neuropsychological capacities (ie, implicit memory) of PwD. At
      the conclusion of the iterative development process, a prototype game with 39
      screens was used for a pilot study with 24 PwD and 14 healthy community dwelling
      older adults. The game was played twice weekly for 10 weeks. RESULTS:
      Quantitative analysis showed that the average speed of successful screen
      completion was significantly longer for PwD compared with healthy older adults.
      Both PwD and controls showed an equivalent linear increase in the speed for task
      completion with practice by the third session (P<.02). Most important, the rate
      of improved processing speed with practice was not statistically different
      between PwD and controls. This may imply that some form of learning occurred for
      PwD at a nonsignificantly different rate than for controls. Qualitative results
      indicate that PwD found the game engaging and fun. Healthy older adults found the
      game too easy. Increase in self-reported self-efficacy was documented with PwD
      only. CONCLUSIONS: Our study demonstrated that PwD's speed improved with practice
      at the same rate as healthy older adults. This implies that when tasks are
      designed to match PwD's abilities, learning ensues. In addition, this pilot study
      of a serious game, designed for PwD, was accessible, acceptable, and enjoyable
      for end users. Games designed based on learning theories and input of end users
      and a multi-disciplinary team familiar with dementia and aging may have the
      potential of maintaining capacity and improving functionality of PwD. A larger
      longer study is needed to confirm our findings and evaluate the use of these
      games in assessing cognitive status and functionality.

PMID- 28760731
TI  - Hepatic Flavin-Containing Monooxygenase 3 Enzyme Suppressed by Type 1 Allergy
      Produced Nitric Oxide.
AB  - Flavin-containing monooxygenases (FMOs) are major mammalian non-cytochrome P450
      oxidative enzymes. T helper 2 cell-activated allergic diseases produce excess
      levels of nitric oxide (NO) that modify the functions of proteins. However, it
      remains unclear whether allergy-induced NO affects the pharmacokinetics of drugs
      metabolized by FMOs. This study investigated alterations of hepatic microsomal
      FMO1 and FMO3 activities in type 1 allergic mice and further examined the
      interaction of FMO1 and FMO3 with allergy-induced NO. Imipramine (IMP; FMO1
      substrate) N-oxidation activity was not altered in allergic mice with high serum
      NO and immunoglobulin E levels. At 7 days after primary sensitization (PS7) or
      secondary sensitization (SS7), benzydamine (BDZ; FMO1 and FMO3 substrate) N
      oxygenation was significantly decreased to 70% of individual controls. The
      expression levels of FMO1 and FMO3 proteins were not significantly changed in the
      sensitized mice. Hepatic inducible NO synthase (iNOS) mRNA level increased 5-fold
      and 15-fold in PS7 and SS7 mice, respectively, and hepatic tumor necrosis factor
      alpha levels were greatly enhanced. When a selective iNOS inhibitor was injected
      into allergic mice, serum NO levels and BDZ N-oxygenation activity returned to
      control levels. NO directly suppressed BDZ N-oxygenation, which was probably
      related to FMO3-dependent metabolism in comparison with IMP N-oxidation. In
      hepatic microsomes from PS7 and SS7 mice, the suppression of BDZ N-oxygenation
      was restored by ascorbate. Therefore, type 1 allergic mice had differentially
      suppressed FMO3-dependent BDZ N-oxygenation. The suppression of FMO3 metabolism
      related to reversible S-nitrosyl modifications of iNOS-derived NO. NO is expected
      to alter FMO3-metabolic capacity-limited drug pharmacokinetics in humans.

PMID- 28760733
TI  - WASP-Arp2/3-dependent actin polymerization influences fusogen localization during
      cell-cell fusion in Caenorhabditiselegans embryos.
AB  - Cell-cell fusion is essential for development and physiology. Actin
      polymerization was implicated in the Caenorhabditiselegans fusogen EFF-1
      engagement in a reconstituted Drosophila cell culture system, and the actin
      binding protein spectraplakin links EFF-1 to the actin cytoskeleton and promotes
      cell-cell fusions in C. elegans larvae. However, it remains unclear whether and
      how fusogens and the actin cytoskeleton are coordinated in C. elegans embryos.
      Here, we used live imaging analysis of GFP knock-in and RNAi embryos to study the
      embryonic cell-cell fusions in C. elegans Our results show that the inhibition of
      WASP-Arp2/3-dependent actin polymerization delays cell-cell fusions. EFF-1 is
      primarily distributed in intracellular vesicles in embryonic fusing cells, and we
      find that the perturbation of actin polymerization reduces the number of EFF-1
      postive vesicles. Thus, the actin cytoskeleton differently promotes cell-cell
      fusion by regulating fusogen localization to the fusing plasma membrane in larvae
      or to intracellular vesicles in embryos.

PMID- 28760732
TI  - Role of NOX2-Derived Reactive Oxygen Species in NK Cell-Mediated Control of
      Murine Melanoma Metastasis.
AB  - The NADPH oxidase of myeloid cells, NOX2, generates reactive oxygen species (ROS)
      to eliminate pathogens and malignant cells. NOX2-derived ROS have also been
      proposed to dampen functions of natural killer (NK) cells and other
      antineoplastic lymphocytes in the microenvironment of established tumors. The
      mechanisms by which NOX2 and ROS influence the process of distant metastasis have
      only been partially explored. Here, we utilized genetically NOX2-deficient mice
      and pharmacologic inhibition of NOX2 to elucidate the role of NOX2 for the
      hematogenous metastasis of melanoma cells. After intravenous inoculation of B16F1
      or B16F10 cells, lung metastasis formation was reduced in B6.129S6-Cybbtm1DinK
      (Nox2-KO) versus Nox2-sufficient wild-type (WT) mice. Systemic treatment with the
      NOX2-inhibitor histamine dihydrochloride (HDC) reduced melanoma metastasis and
      enhanced the infiltration of IFNgamma-producing NK cells into lungs of WT but not
      of Nox2-KO mice. IFNgamma-deficient B6.129S7-Ifngtm1Ts /J mice were prone to
      develop melanoma metastases and did not respond to in vivo treatment with HDC. We
      propose that NOX2-derived ROS facilitate metastasis of melanoma cells by
      downmodulating NK-cell function and that inhibition of NOX2 may restore IFNgamma
      dependent, NK cell-mediated clearance of melanoma cells. Cancer Immunol Res;
      5(9); 804-11. (c)2017 AACR.

PMID- 28760734
TI  - An ex vivo model using human peritoneum to explore mesh-tissue integration.
AB  - Biological compatibility, in terms of implantation of foreign mesh material in
      hernia surgery, still needs experimental investigation. The present study
      develops an experimental model using human peritoneum to study the integration
      between tissue and different mesh material. The ex vivo model using peritoneal
      tissue was studied with different mesh material, and integration was monitored
      over time using microscopy. The peritoneal model could be kept viable in culture
      for several weeks. Cell migration was seen after 7-10 days in culture and could
      be further monitored over several weeks. The use of a human artificial model
      environment enabling the investigation of tissue/mesh integration has, to our
      knowledge, not been described previously. This proof-of-concept model was
      developed for the investigation of peritoneal biology and the integration between
      tissue and different mesh material. It has the potential to be useful in studies
      on other important biological mechanisms involving the peritoneum.

PMID- 28760735
TI  - Metabolomics reveals variation and correlation among different tissues of olive
      (Olea europaea L.).
AB  - Metabolites in olives are associated with nutritional value and physiological
      properties. However, comprehensive information regarding the olive metabolome is
      limited. In this study, we identified 226 metabolites from three different
      tissues of olive using a non-targeted metabolomic profiling approach, of which 76
      named metabolites were confirmed. Further statistical analysis revealed that
      these 76 metabolites covered different types of primary metabolism and some of
      the secondary metabolism pathways. One-way analysis of variance (ANOVA)
      statistical assay was performed to calculate the variations within the detected
      metabolites, and levels of 65 metabolites were differentially expressed in
      different samples. Hierarchical cluster analysis (HCA) dendrograms showed
      variations among different tissues that were similar to the metabolite profiles
      observed in new leaves and fruit. Additionally, 5776 metabolite-metabolite
      correlations were detected by a Pearson correlation coefficient approach.
      Screening of the calculated correlations revealed 3136, 3025, and 5184 were
      determined to metabolites and had significant correlations in three different
      combinations, respectively. This work provides the first comprehensive
      metabolomic of olive, which will provide new insights into understanding the
      olive metabolism, and potentially help advance studies in olive metabolic
      engineering.

PMID- 28760736
TI  - Targeting long non-coding RNA DANCR inhibits triple negative breast cancer
      progression.
AB  - Triple negative breast cancer (TNBC) is non-responsive to conventional anti
      hormonal and Her2-targeted therapies, making it necessary to identify new
      molecular targets for therapy. Long non-coding RNA anti-differentiation ncRNA
      (lncRNA DANCR) was identified participating in carcinogenesis of hepatocellular
      carcinoma, but its expression and potential role in TNBC progression is still
      unclear. In the present study, our results showed that DANCR expression was
      increased in TNBC tissues compared with the adjacent normal tissues using
      quantitative real-time PCR (qRT-PCR) in 63 TNBC specimens. Patients with higher
      DANCR expression correlated with worse TNM stages as well as a shorter overall
      survival (OS) using Kaplan-Meier analysis. When the endogenous DANCR was knocked
      down via specific siRNA, cell proliferation and invasion were decreased obviously
      in the MDA-MB-231 cells. In vivo xenograft experiments showed that knockdown of
      the DANCR in MDA-MB-231 cells reduced the tumor growth significantly.
      Furthermore, a compendium of TNBC cancer stem cell markers such as CD44, ABCG2
      transporter and aldehyde dehydrogenase (ALDH1) were greatly downregulated in the
      MDA-MB-231 cells with DANCR knockdown. Molecular mechanistic studies revealed
      that knockdown of DANCR was associated with increased binding of EZH2 on the
      promoters of CD44 and ABCG2, and concomitant reduction of expression of these
      genes suggested that they may be DANCR targets in TNBC. Thus, our study
      demonstrated that targeting DANCR expression might be a viable therapeutic
      approach to treat triple negative breast cancer.

PMID- 28760737
TI  - Docetaxel Reverses Pulmonary Vascular Remodeling by Decreasing Autophagy and
      Resolves Right Ventricular Fibrosis.
AB  - Pulmonary arterial hypertension remains a fatal disease despite the availability
      of approved vasodilators. Since vascular remodeling contributes to increased
      pulmonary arterial pressure, new agents that reduce the thickness of pulmonary
      vascular walls have therapeutic potential. Thus, antitumor agents that are
      capable of killing cells were investigated. Testing of various antitumor drugs
      identified that docetaxel is a superior drug for killing proliferating pulmonary
      artery smooth muscle cells compared with other drugs, including gemcitabine,
      methotrexate, and ifosfamide. The administration of docetaxel to rats with severe
      pulmonary arterial hypertension reversed pulmonary vascular remodeling and
      reduced right ventricular pressure. Docetaxel was found to decrease autophagy as
      monitored by LC3B-II and p62 expression. The small interfering RNA knockdown of
      Beclin-1 or LC3B potentiated docetaxel-induced cell death, and knocking down p62
      inhibited the docetaxel effects. The suppressed autophagic process is due to the
      ability of docetaxel to decrease Beclin-1 protein expression in a proteasome
      dependent manner. Mass spectrometry identified a novel docetaxel-inducible Beclin
      1 binding protein, namely, myosin-9. Knocking down myosin-9 inhibited docetaxel
      induced cell death. In damaged right ventricles of pulmonary arterial
      hypertension rats, docetaxel remarkably promoted the resolution of fibrosis and
      the regeneration of myocardium. Thus, docetaxel is capable of reversing pulmonary
      vascular remodeling and resolving right ventricle fibrosis and is a promising
      therapeutic agent for the treatment of pulmonary arterial hypertension and right
      heart failure.

PMID- 28760738
TI  - Characteristics associated with joint replacement in early symptomatic knee or
      hip osteoarthritis: 6-year results from a nationwide prospective cohort study
      (CHECK).
AB  - BACKGROUND: Many patients with osteoarthritis (OA) of the knee and/or hip undergo
      total joint replacement (TJR) because of severely progressed symptoms. AIM: To
      determine patient and disease characteristics associated with undergoing TJR in
      participants with recent-onset knee and/or hip OA. DESIGN AND SETTING:
      Participants with hip or knee pain from the nationwide prospective Cohort Hip and
      Cohort Knee (CHECK) study were included. METHOD: The outcome measure was total
      hip arthroplasty (THA) or total knee arthroplasty (TKA) during 6 years of follow
      up. Joint-dependent characteristics were compared using generalised estimating
      equations (GEE). Multivariable models were built for both subgroups. Differences
      in symptomatic and radiographic progression were determined between baseline and
      2-year follow-up (T2). RESULTS: The knee subgroup included 751 participants (1502
      knees), and there were 538 participants in the hip subgroup (1076 hips). Nineteen
      participants (22 knees) underwent TKA and 53 participants (62 hips) THA.
      Participants who underwent TKA had higher baseline body mass index, painful knee
      flexion, and higher Kellgren and Lawrence scores. Participants who underwent THA
      had painful internal hip rotation and showed more severe radiographic OA
      features. Participants who underwent TKA or THA showed more rapid symptomatic and
      radiographic OA progression at T2. CONCLUSION: In patients with recent-onset knee
      or hip pain, radiographic OA features already exist and a substantial number of
      patients fulfil existing criteria for knee and hip OA. A trend was observed in
      rapid progression of radiographic and symptomatic OA severity among patients with
      TKA and THA. Early detection of OA by the GP is important in managing knee and
      hip OA.

PMID- 28760739
TI  - Comparison between treatment effects in a randomised controlled trial and an
      observational study using propensity scores in primary care.
AB  - BACKGROUND: Although randomised controlled trials (RCTs) are considered 'gold
      standard' evidence, they are not always feasible or appropriate, and may
      represent a select population. Observational studies provide a useful alternative
      to enhance applicability, but results can be biased due to confounding. AIM: To
      explore the utility of propensity scores for causal inference in an observational
      study. DESIGN AND SETTING: Comparison of the effect of amoxicillin on key
      outcomes in an international RCT and observational study of lower respiratory
      tract infections. METHOD: Propensity scores were calculated and applied as
      probability weights in the analyses. The adjusted results were compared with the
      effects reported in the RCT. RESULTS: Groups were well balanced in the RCT but
      significantly imbalanced in the observational study, with evidence of confounding
      by indication: patients receiving antibiotics tended to be older and more unwell
      at baseline consultation. In the trial duration of symptoms (hazard ratio 1.06,
      95% CI = 0.96 to 1.18) and symptom severity (-0.07, 95% CI = -0.15 to 0.007) did
      not differ between groups. Weighting by propensity score in the observational
      study resulted in very similar estimates of effect: duration of symptoms (hazard
      ratio 1.06, 95% CI = 0.80 to 1.40) and difference for symptom severity (-0.07,
      95% CI = -0.34 to 0.20). CONCLUSION: The observational study, after conditioning
      on propensity score, echoed the trial results. Provided that detailed information
      is available on potential sources of confounding, effects of interventions can
      probably be assessed reasonably well in observational datasets, allowing them to
      be more directly compared with the results of RCTs.

PMID- 28760740
TI  - Impact of initial medication non-adherence on use of healthcare services and sick
      leave: a longitudinal study in a large primary care cohort in Spain.
AB  - BACKGROUND: Initial medication non-adherence is highly prevalent in primary care
      but no previous studies have evaluated its impact on the use of healthcare
      services and/or days on sick leave. AIM: To estimate the impact of initial
      medication non-adherence on the use of healthcare services, days of sick leave,
      and costs overall and in specific medication groups. DESIGN AND SETTING: A 3-year
      longitudinal register-based study of all primary care patients (a cohort of 1.7
      million) who were prescribed a new medication in Catalonia (Spain) in 2012.
      METHOD: Thirteen of the most prescribed and/or costly medication subgroups were
      considered. All medication and medication subgroups (chronic, analgesics, and
      penicillin) were analysed. The number of healthcare services used and days on
      sick leave were considered. Multilevel multivariate linear regression was used.
      Three levels were included: patient, GP, and primary care centre. RESULTS:
      Initially adherent patients made more use of medicines and some healthcare
      services than non-adherent and partially adherent patients. They had lower
      productivity losses, producing a net economic return, especially when drugs for
      acute diseases (such as penicillins) were considered. Initial medication non
      adherence resulted in a higher economic burden to the system in the short term.
      CONCLUSION: Initial medication non-adherence seems to have a short-term impact on
      productivity losses and costs. The clinical consequences and long-term economic
      consequences of initial medication non-adherence need to be assessed.
      Interventions to promote initial medication adherence in primary care may reduce
      costs and improve health outcomes.

PMID- 28760741
TI  - Application of the 2014 NICE cholesterol guidelines in the English population: a
      cross-sectional analysis.
AB  - BACKGROUND: The 2014 guidelines on cardiovascular risk assessment and lipid
      modification from the National Institute for Health and Care Excellence (NICE)
      recommend statin therapy for adults with prevalent cardiovascular disease (CVD),
      and for adults with a 10-year CVD risk of >=10%, estimated using the QRISK2
      algorithm. AIM: To determine risk factor levels required to exceed the risk
      threshold for statin therapy, and to estimate the number of adults in England who
      would require statin therapy under the guidelines. DESIGN AND SETTING: Cross
      sectional study using a sample representative of the English population aged 30
      84 years. METHOD: To estimate 10-year CVD risk different combinations of risk
      factor levels were entered into the QRISK2 algorithm. The NICE guidelines were
      applied to the sample using data from the Health Survey for England 2011.
      RESULTS: Even with optimal risk factor levels, males of different ethnicities
      would exceed the 10% risk threshold between the ages of 60 and 70 years, and
      females would exceed the threshold between 65 and 75 years. Under the NICE
      guidelines, 11.8 million males and females (37% of the adults aged 30-84 years)
      would require statin therapy, most of them (9.8 million) for primary prevention.
      When analysed by age, 95% of males and 66% of females without CVD in ages 60-74
      years, including all males and females in ages 75-84 years, would require statin
      therapy. CONCLUSION: Under the 2014 NICE guidelines, 11.8 million (37%) adults in
      England aged 30-84 years, including almost all males >60 years in all females >75
      years, require statin therapy.

PMID- 28760742
TI  - All-Cause and Specific-Cause Mortality Risk After Roux-en-Y Gastric Bypass in
      Patients With and Without Diabetes.
AB  - OBJECTIVE: This study assessed all-cause and specific-cause mortality after Roux
      en-Y gastric bypass (RYGB) and in matched control subjects, stratified by
      diabetes status. RESEARCH DESIGN AND METHODS: RYGB patients were matched by age,
      BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects
      using data from the electronic health record. Kaplan-Meier curves and Cox
      regression were used to assess differences in all-cause and specific-cause
      mortality between RYGB patients and control subjects with and without diabetes.
      RESULTS: Of the 3,242 eligible RYGB patients enrolled from January 2004 to
      December 2015, control subjects were identified for 2,428 (n = 625 with diabetes
      and n = 1,803 without diabetes). Median postoperative follow-up was 5.8 years for
      patients with diabetes and 6.7 years for patients without diabetes. All-cause
      mortality was reduced in RYGB patients compared with control subjects only for
      those with diabetes at the time of surgery (adjusted hazard ratio 0.44; P <
      0.0001). Mortality was not significantly improved in RYGB patients without
      diabetes compared with control subjects without diabetes (adjusted hazard ratio
      0.84; P = 0.37). Deaths from cardiovascular diseases (P = 0.011), respiratory
      conditions (P = 0.017), and diabetes P = 0.011) were more frequent in control
      subjects with diabetes than in RYGB patients with diabetes. RYGB patients without
      diabetes were less likely to die of cancer (P = 0.0038) and respiratory diseases
      (P = 0.046) than control subjects without diabetes but were at higher risk of
      death from external causes (P = 0.012), including intentional self-harm (P =
      0.025), than control subjects without diabetes. CONCLUSIONS: All-cause mortality
      benefits of RYGB are driven predominantly by patients with diabetes at the time
      of surgery. RYGB patients with diabetes were less likely to die of cardiovascular
      diseases, diabetes, and respiratory conditions than their counterparts without
      RYGB.

PMID- 28760743
TI  - Hypoxia-inducible protein 2 Hig2/Hilpda mediates neutral lipid accumulation in
      macrophages and contributes to atherosclerosis in apolipoprotein E-deficient
      mice.
AB  - Recently we identified hypoxia-inducible protein 2 (HIG2)/hypoxia-inducible lipid
      droplet-associated (HILPDA) as lipid droplet (LD) protein. Because HILPDA is
      highly expressed in atherosclerotic plaques, we examined its regulation and
      function in murine macrophages, compared it to the LD adipose differentiation
      related protein (Adrp)/perilipin 2 (Plin2), and investigated its effects on
      atherogenesis in apolipoprotein E-deficient (ApoE-/-) mice. Tie2-Cre-driven
      Hilpda conditional knockout (cKO) did not affect viability, proliferation, and
      ATP levels in macrophages. Hilpda proved to be a target of hypoxia-inducible
      factor 1 (Hif-1) and peroxisome proliferator-activated receptors. In contrast,
      Adrp/Plin2 was not induced by Hif-1. Hilpda localized to the endoplasmic
      reticulum-LD interface, the site of LD formation. Hypoxic lipid accumulation and
      storage of oxidized LDL, cholesteryl esters and triglycerides were abolished in
      Hilpda cKO macrophages, independent of the glycolytic switch, fatty acid or
      lipoprotein uptake. Hilpda depletion reduced resistance against lipid overload
      and increased production of reactive oxygen species after reoxygenation. LPS
      stimulated prostaglandin-E2 production was dysregulated in macrophages,
      demonstrating the substrate buffer and reservoir function of LDs for eicosanoid
      production. In ApoE-/- Hilpda cKO mice, total aortic plaque area, plaque
      macrophages and vascular Vegf expression were reduced. Thus, macrophage Hilpda is
      crucial to foam-cell formation and lipid deposition, and to controlled
      prostaglandin-E2 production. By these means Hilpda promotes lesion formation and
      progression of atherosclerosis.-Maier, A., Wu, H., Cordasic, N., Oefner, P.,
      Dietel, B., Thiele, C., Weidemann, A., Eckardt, K.-U., Warnecke, C. Hypoxia
      inducible protein 2 Hig2/Hilpda mediates neutral lipid accumulation in
      macrophages and contributes to atherosclerosis in apolipoprotein E-deficient
      mice.

PMID- 28760744
TI  - Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid
      desaturation in Caenorhabditis elegans.
AB  - The incidence of obesity is rising at an alarming rate. Despite its recognition
      as an urgent healthcare concern, obesity remains largely an unsolved medical
      problem. A comprehensive screen for functional dietary phytochemicals identified
      proanthocyanidins as putative targets to ameliorate obesity. A full-scale
      purification of oligomeric proanthocyanidins (OPCs) derived from grape seed
      extract yielded pure OPC dimer, trimer, tetramer, and their gallates (pOPCs).
      Forward chemical screening conducted in Caenorhabditis elegans suggested that
      pOPCs reduced the activity of lipase in vitro and triglyceride storage capacity
      in vivo Proanthocyanidin trimer gallate in particular modified lipid desaturation
      in C. elegans, revealed by hyperspectral coherent anti-Stokes Raman scattering
      microscopy. Exposure to trimer gallate resulted in the transcriptional down
      regulation of nhr-49 (an ortholog of the human peroxisome proliferator-activated
      receptor-alpha), and a key regulator of fat metabolism, and 2 downstream genes:
      fat-5 and acs-2 A combination exposure of 2 or 3 pOPCs (dimer gallate, trimer
      and/or trimer gallate) suggested the absence of synergistic potential. By using
      the whole-organism C. elegans coupled with versatile biochemical, biophysical,
      and genetic tools, we provide an account of the composition and bioactivity of
      individual OPCs and more generally highlight the potential of traditional Chinese
      medicine-derived drug leads.-Nie, Y., Littleton, B., Kavanagh, T., Abbate, V.,
      Bansal, S. S., Richards, D., Hylands, P., Sturzenbaum, S. R. Proanthocyanidin
      trimer gallate modulates lipid deposition and fatty acid desaturation in
      Caenorhabditis elegans.

PMID- 28760745
TI  - A PP2A-mediated feedback mechanism controls Ca2+-dependent NO synthesis under
      physiological oxygen.
AB  - Intracellular O2 is a key regulator of NO signaling, yet most in vitro studies
      are conducted in atmospheric O2 levels, hyperoxic with respect to the physiologic
      milieu. We investigated NO signaling in endothelial cells cultured in physiologic
      (5%) O2 and stimulated with histamine or shear stress. Culture of cells in 5% O2
      (>5 d) decreased histamine- but not shear stress-stimulated endothelial (e)NOS
      activity. Unlike cells adapted to a hypoxic environment (1% O2), those cultured
      in 5% O2 still mobilized sufficient Ca2+ to activate AMPK. Enhanced expression
      and membrane targeting of PP2A-C was observed in 5% O2, resulting in greater
      interaction with eNOS in response to histamine. Moreover, increased
      dephosphorylation of eNOS in 5% O2 was Ca2+-sensitive and reversed by okadaic
      acid or PP2A-C siRNA. The present findings establish that Ca2+ mobilization
      stimulates both NO synthesis and PP2A-mediated eNOS dephosphorylation, thus
      constituting a novel negative feedback mechanism regulating eNOS activity not
      present in response to shear stress. This, coupled with enhanced NO
      bioavailability, underpins differences in NO signaling induced by inflammatory
      and physiologic stimuli that are apparent only in physiologic O2 levels.
      Furthermore, an explicit delineation between physiologic normoxia and genuine
      hypoxia is defined here, with implications for our understanding of
      pathophysiological hypoxia.-Keeley, T. P., Siow, R. C. M., Jacob, R., Mann, G. E.
      A PP2A-mediated feedback mechanism controls Ca2+-dependent NO synthesis under
      physiological oxygen.

PMID- 28760746
TI  - Insights into the Evolution and Function of Auxin Signaling F-Box Proteins in
      Arabidopsis thaliana Through Synthetic Analysis of Natural Variants.
AB  - The evolution of complex body plans in land plants has been paralleled by gene
      duplication and divergence within nuclear auxin-signaling networks. A deep
      mechanistic understanding of auxin signaling proteins therefore may allow
      rational engineering of novel plant architectures. Toward that end, we analyzed
      natural variation in the auxin receptor F-box family of wild accessions of the
      reference plant Arabidopsis thaliana and used this information to populate a
      structure/function map. We employed a synthetic assay to identify natural
      hypermorphic F-box variants and then assayed auxin-associated phenotypes in
      accessions expressing these variants. To more directly measure the impact of the
      strongest variant in our synthetic assay on auxin sensitivity, we generated
      transgenic plants expressing this allele. Together, our findings link evolved
      sequence variation to altered molecular performance and auxin sensitivity. This
      approach demonstrates the potential for combining synthetic biology approaches
      with quantitative phenotypes to harness the wealth of available sequence
      information and guide future engineering efforts of diverse signaling pathways.

PMID- 28760747
TI  - Significant Synteny and Colocalization of Ecologically Relevant Quantitative
      Trait Loci Within and Across Species of Salmonid Fishes.
AB  - The organization of functional regions within genomes has important implications
      for evolutionary potential. Considerable research effort has gone toward
      identifying the genomic basis of phenotypic traits of interest through
      quantitative trait loci (QTL) analyses. Less research has assessed the
      arrangement of QTL in the genome within and across species. To investigate the
      distribution, extent of colocalization, and the synteny of QTL for ecologically
      relevant traits, we used a comparative genomic mapping approach within and across
      a range of salmonid species. We compiled 943 QTL from all available species [lake
      whitefish (Coregonus clupeaformis), coho salmon (Oncorhynchus kisutch), rainbow
      trout (O. mykiss), Chinook salmon (O. tshawytscha), Atlantic salmon (Salmo
      salar), and Arctic charr (Salvelinus alpinus)]. We developed a novel analytical
      framework for mapping and testing the distribution of these QTL. We found no
      correlation between QTL density and gene density at the chromosome level but did
      at the fine-scale. Two chromosomes were significantly enriched for QTL. We found
      multiple synteny blocks for morphological, life history, and physiological traits
      across species, but only morphology and physiology had significantly more than
      expected. Two or three pairs of traits were significantly colocalized in three
      species (lake whitefish, coho salmon, and rainbow trout). Colocalization and fine
      scale synteny suggest genetic linkage between traits within species and a
      conserved genetic basis across species. However, this pattern was weak overall,
      with colocalization and synteny being relatively rare. These findings advance our
      understanding of the role of genomic organization in the renowned ecological and
      phenotypic variability of salmonid fishes.

PMID- 28760749
TI  - Margaret McCartney: Alarm overload makes a difficult job harder.

PMID- 28760748
TI  - Impact of age, sex and body mass index on cortisol secretion in 143 healthy
      adults.
AB  - CONTEXT: Studies on 24-h cortisol secretion are rare. The impact of sex, age and
      adiposity on cortisol levels, often restricted to one or a few samples, are well
      recognized, but conflicting. OBJECTIVE: To investigate cortisol dynamics in 143
      healthy men and women, spanning 7 decades and with a 2-fold body mass index (BMI)
      range with different analytic tools. SETTING: Clinical Research Unit. DESIGN:
      Cortisol concentrations in 10-min samples collected for 24 h. Outcomes were mean
      levels, deconvolution parameters, approximate entropy (ApEn, regularity
      statistic) and 24-h rhythms. RESULTS: Total 24-h cortisol secretion rates
      estimated by deconvolution analysis were sex, age and BMI independent. Mean 24-h
      cortisol concentrations were lower in premenopausal women than those in men of
      comparable age (176 +/- 8.2 vs 217 +/- 9.4 nmol/L, P = 0.02), but not in subjects
      older than 50 years. This was due to lower daytime levels in women, albeit
      similar in the quiescent overnight period. Aging increased mean cortisol by 10
      nmol/L per decade during the quiescent secretory phase and advanced the acrophase
      of the diurnal rhythm by 24 min/decade. However, total 24-h cortisol secretion
      rates estimated by deconvolution analysis were sex, age and BMI independent. ApEn
      of 24-h profiles was higher (more random) in premenopausal women than those in
      men (1.048 +/- 0.025 vs 0.933 +/- 0.023, P = 0.001), but not in subjects older
      than 50 years. ApEn peaked during the daytime. CONCLUSION: Sex and age jointly
      determine the 24-h cortisol secretory profile. Sex effects are largely restricted
      to age <50 years, whereas age effects elevate concentrations in the late evening
      and early night and advance the timing of the peak diurnal rhythm.

PMID- 28760750
TI  - The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement,
      Diagnosis, and Prediction: A Scientific Statement From the American Heart
      Association.
AB  - There have been major advances in our knowledge of the contribution of DNA
      sequence variations to cardiovascular disease and stroke. However, the inner
      workings of the body reflect the complex interplay of factors beyond the DNA
      sequence, including epigenetic modifications, RNA transcripts, proteins, and
      metabolites, which together can be considered the "expressed genome." The
      emergence of high-throughput technologies, including epigenomics,
      transcriptomics, proteomics, and metabolomics, is now making it possible to
      address the contributions of the expressed genome to cardiovascular disorders.
      This statement describes how the expressed genome can currently and, in the
      future, potentially be used to diagnose diseases and to predict who will develop
      diseases such as coronary artery disease, stroke, heart failure, and arrhythmias.

PMID- 28760752
TI  - BMA should suspend perpetrators of social media abuse.

PMID- 28760751
TI  - Multitarget Therapy for Maintenance Treatment of Lupus Nephritis.
AB  - Our previous studies showed that multitarget therapy is superior in efficacy to
      intravenous cyclophosphamide as an induction treatment for lupus nephritis in
      Asian populations. We conducted an open label, multicenter study for 18 months as
      an extension of the prior induction therapy trial in 19 renal centers in China to
      assess the efficacy and safety of multitarget maintenance therapy in patients who
      had responded at 24 weeks during the induction phase. Patients who had undergone
      multitarget induction therapy continued to receive multitarget therapy
      (tacrolimus, 2-3 mg/d; mycophenolate mofetil, 0.50-0.75 g/d; prednisone, 10
      mg/d), and patients who had received intravenous cyclophosphamide induction
      treatment received azathioprine (2 mg/kg per day) plus prednisone (10 mg/d). We
      assessed the renal relapse rate during maintenance therapy as the primary
      outcome. We recruited 116 patients in the multitarget group and 90 patients in
      the azathioprine group. The multitarget and azathioprine groups had similar
      cumulative renal relapse rates (5.47% versus 7.62%, respectively; adjusted hazard
      ratio, 0.82; 95% confidence interval, 0.25 to 2.67; P=0.74), and serum creatinine
      levels and eGFR remained stable in both groups. The azathioprine group had more
      adverse events (44.4% versus 16.4% for multitarget therapy; P<0.01), and the
      multitarget group had a lower withdrawal rate due to adverse events (1.7% versus
      8.9% for azathioprine; P=0.02). In conclusion, multitarget therapy as a
      maintenance treatment for lupus nephritis resulted in a low renal relapse rate
      and fewer adverse events, suggesting that multitarget therapy is an effective and
      safe maintenance treatment for patients with lupus nephritis.

PMID- 28760753
TI  - Adult sex ratios and reproductive strategies: a critical re-examination of sex
      differences in human and animal societies.
AB  - It is increasingly recognized that the relative proportion of potential mates to
      competitors in a population impacts a range of sex-specific behaviours and in
      particular mating and reproduction. However, while the adult sex ratio (ASR) has
      long been recognized as an important link between demography and behaviour, this
      relationship remains understudied. Here, we introduce the first inter
      disciplinary collection of research on the causes and consequences of variation
      in the ASR in human and animal societies. This important topic is relevant to a
      wide audience of both social and biological scientists due to the central role
      that the relative number of males to females in a population plays for the
      evolution of, and contemporary variation in, sex roles across groups, species and
      higher taxa. The articles in this theme issue cover research on ASR across a
      variety of taxa and topics. They offer critical re-evaluations of theoretical
      foundations within both evolutionary and non-evolutionary fields, and propose
      innovative methodological approaches, present new empirical examples of
      behavioural consequences of ASR variation and reveal that the ASR plays a major
      role in determining population viability, especially in small populations and
      species with labile sex determination. This introductory paper puts the
      contributions of the theme issue into a broader context, identifies general
      trends across the literature and formulates directions for future research.This
      article is part of the themed issue 'Adult sex ratios and reproductive decisions:
      a critical re-examination of sex differences in human and animal societies'.

PMID- 28760754
TI  - Reproductive competition and sexual selection.
AB  - This paper traces the development of our understanding of the development of
      different approaches to estimating the strength of reproductive competition and
      sexual selection in the two sexes, based on measures of the operational sex
      ratio, the opportunity for sexual selection and contrasts in selection gradients
      between the sexes. It argues that different approaches provide complementary
      insights into the causes of sex differences in reproductive competition, the
      operation of sexual selection and the evolution of secondary sexual characters
      and that improvements in our understanding of the evolution of secondary sexual
      characters will require a more comprehensive understanding of the ways in which
      social and ecological conditions modify reproductive competition and development
      in females and males.This article is part of the themed issue 'Adult sex ratios
      and reproductive decisions: a critical re-examination of sex differences in human
      and animal societies'.

PMID- 28760755
TI  - Not all sex ratios are equal: the Fisher condition, parental care and sexual
      selection.
AB  - The term 'sex roles' encapsulates male-female differences in mate searching,
      competitive traits that increase mating/fertilization opportunities, choosiness
      about mates and parental care. Theoretical models suggest that biased sex ratios
      drive the evolution of sex roles. To model sex role evolution, it is essential to
      note that in most sexually reproducing species (haplodiploid insects are an
      exception), each offspring has one father and one mother. Consequently, the total
      number of offspring produced by each sex is identical, so the mean number of
      offspring produced by individuals of each sex depends on the sex ratio (Fisher
      condition). Similarly, the total number of heterosexual matings is identical for
      each sex. On average, neither sex can mate nor breed more often when the sex
      ratio is even. But equally common in which sex ratio? The Fisher condition only
      applies to some reproductive measures (e.g. lifetime offspring production or
      matings) for certain sex ratios (e.g. operational or adult sex ratio; OSR, ASR).
      Here, we review recent models that clarify whether a biased OSR, ASR or sex ratio
      at maturation (MSR) have a causal or correlational relationship with the
      evolution of sex differences in parental care and competitive traits-two key
      components of sex roles. We suggest that it is more fruitful to understand the
      combined effect of the MSR and mortality rates while caring and competing than
      that of the ASR itself. In short, we argue that the ASR does not have a causal
      role in the evolution of parental care. We point out, however, that the ASR can
      be a cue for adaptive phenotypic plasticity in how each sex invests in parental
      care.This article is part of the themed issue 'Adult sex ratios and reproductive
      decisions: a critical re-examination of sex differences in human and animal
      societies'.

PMID- 28760756
TI  - Estimating adult sex ratios in nature.
AB  - Adult sex ratio (ASR, the proportion of males in the adult population) is a
      central concept in population and evolutionary biology, and is also emerging as a
      major factor influencing mate choice, pair bonding and parental cooperation in
      both human and non-human societies. However, estimating ASR is fraught with
      difficulties stemming from the effects of spatial and temporal variation in the
      numbers of males and females, and detection/capture probabilities that differ
      between the sexes. Here, we critically evaluate methods for estimating ASR in
      wild animal populations, reviewing how recent statistical advances can be applied
      to handle some of these challenges. We review methods that directly account for
      detection differences between the sexes using counts of unmarked individuals
      (observed, trapped or killed) and counts of marked individuals using mark
      recapture models. We review a third class of methods that do not directly sample
      the number of males and females, but instead estimate the sex ratio indirectly
      using relationships that emerge from demographic measures, such as survival, age
      structure, reproduction and assumed dynamics. We recommend that detection-based
      methods be used for estimating ASR in most situations, and point out that studies
      are needed that compare different ASR estimation methods and control for sex
      differences in dispersal.This article is part of the themed issue 'Adult sex
      ratios and reproductive decisions: a critical re-examination of sex differences
      in human and animal societies'.

PMID- 28760757
TI  - Causes and consequences of adult sex ratio imbalance in a historical U.S.
      population.
AB  - The responsiveness of individuals to partner availability has been well
      documented across the literature. However, there is disagreement regarding the
      direction of the consequences of sex ratio imbalance. Specifically, does an
      excess of males or females promote male-male mating competition? In an attempt to
      clarify the role of the adult sex ratio (ASR) on behaviour, here we evaluate both
      competing and complimentary expectations derived from theory across the social
      and biological sciences. We use data drawn from a historical, nineteenth century
      population in North America and target several life-history traits thought to be
      affected by partner availability: age at first birth, relationship status,
      completed fertility and longevity. Furthermore, we assess the role of various
      contributors to a population's ASR. We find that both the contributors to and
      consequences of sex ratio imbalance vary over time. Our results largely support
      predictions of greater male pairbond commitment and lesser male mating effort, as
      well as elevated bargaining power of women in response to female scarcity. After
      reviewing our findings, and others from across the literature, we highlight the
      need to adjust predictions in response to ASR imbalance by the: (i) culturally
      mediated mating arena, (ii) variable role of demographic inputs across time and
      place, (iii) constraints to behavioural outcomes across populations, and (iv)
      ability and accuracy of individuals to assess partner availability.This article
      is part of the themed issue 'Adult sex ratios and reproductive strategies: a
      critical re-examination of sex differences in human and animal societies'.

PMID- 28760758
TI  - Persistent effect of sex ratios on relationship quality and life satisfaction.
AB  - Convict transportation to Australia imposed heavily male-biased sex ratios in
      some areas, altering the convict-era mating market and generating long-running
      cultural effects that persist to the present day. We test whether convict-era sex
      ratios have altered marital and overall life satisfaction today, through their
      persistent effects on gender norms and household bargaining. We find that both
      women and men are happier, and the happiness gap within married couples is
      smaller in areas where convict-era sex ratios were heavily male-biased than in
      areas where sex ratios were historically more even. We discuss our results in
      light of household bargaining theory, evolutionary sexual conflict theory and the
      well-documented relationship between conservative attitudes and self-reported
      happiness.This article is part of the themed issue 'Adult sex ratios and
      reproductive decisions: a critical re-examination of sex differences in human and
      animal societies'.

PMID- 28760760
TI  - The potential pitfalls of studying adult sex ratios at aggregate levels in
      humans.
AB  - Human adult sex ratios have been studied extensively across the biological and
      social sciences. While several studies have examined adult sex ratio effects in a
      multilevel perspective, many studies have focused on effects at an aggregated
      level only. In this paper, we review some key issues relating to such analyses.
      We address not only nation-level analyses, but also aggregation at lower levels,
      to investigate whether these issues extend to lower levels of aggregation. We
      illustrate these issues with novel databases covering a broad range of variables.
      Specifically, we discuss distributional issues with aggregated measures of adult
      sex ratio, significance testing, and statistical non-independence when using
      aggregate data. Firstly, we show that there are severe distributional issues with
      national adult sex ratio, such as extreme cases. Secondly, we demonstrate that
      many 'meaningless' variables are significantly correlated with adult sex ratio
      (e.g. the max. elevation level correlates with sex ratio at US state level).
      Finally, we re-examine associations between adult sex ratios and teenage
      fertility and find no robust evidence for an association at the aggregate level.
      Our review highlights the potential issues of using aggregate data on adult sex
      ratios to test hypotheses from an evolutionary perspective in humans.This article
      is part of the themed issue 'Adult sex ratios and reproductive decisions: a
      critical re-examination of sex differences in human and animal societies'.

PMID- 28760759
TI  - Adult sex ratios and partner scarcity among hunter-gatherers: implications for
      dispersal patterns and the evolution of human sociality.
AB  - Small populations are susceptible to high genetic loads and random fluctuations
      in birth and death rates. While these selective forces can adversely affect their
      viability, small populations persist across taxa. Here, we investigate the
      resilience of small groups to demographic uncertainty, and specifically to
      fluctuations in adult sex ratio (ASR), partner availability and dispersal
      patterns. Using 25 years of demographic data for two Savannah Pume groups of
      South American hunter-gatherers, we show that in small human populations: (i)
      ASRs fluctuate substantially from year to year, but do not consistently trend in
      a sex-biased direction; (ii) the primary driver of local variation in partner
      availability is stochasticity in the sex ratio at maturity; and (iii) dispersal
      outside of the group is an important behavioural means to mediate locally
      constrained mating options. To then simulate conditions under which dispersal
      outside of the local group may have evolved, we develop two mathematical models.
      Model results predict that if the ASR is biased, the globally rarer sex should
      disperse. The model's utility is then evaluated by applying our empirical data to
      this central prediction. The results are consistent with the observed hunter
      gatherer pattern of variation in the sex that disperses. Together, these findings
      offer an alternative explanation to resource provisioning for the evolution of
      traits central to human sociality (e.g. flexible dispersal, bilocal post-marital
      residence and cooperation across local groups). We argue that in small
      populations, looking outside of one's local group is necessary to find a mate and
      that, motivated by ASR imbalance, the alliances formed to facilitate the movement
      of partners are an important foundation for the human-typical pattern of network
      formation across local groups.This article is part of the themed issue 'Adult sex
      ratios and reproductive decisions: a critical re-examination of sex differences
      in human and animal societies'.

PMID- 28760761
TI  - Adult sex ratio and social status predict mating and parenting strategies in
      Northern Ireland.
AB  - Evidence from animal species indicates that a male-biased adult sex ratio (ASR)
      can lead to higher levels of male parental investment and that there is
      heterogeneity in behavioural responses to mate scarcity depending on mate value.
      In humans, however, there is little consistent evidence of the effect of the ASR
      on pair-bond stability and parental investment and even less of how it varies by
      an individual's mate value. In this paper we use detailed census data from
      Northern Ireland to test the association between the ASR and pair-bond stability
      and parental investment by social status (education and social class) as a proxy
      for mate value. We find evidence that female, but not male, cohabitation is
      associated with the ASR. In female-biased areas women with low education are less
      likely to be in a stable pair-bond than highly educated women, but in male-biased
      areas women with the lowest education are as likely to be in a stable pair-bond
      as their most highly educated peers. For both sexes risk of separation is greater
      at female-biased sex ratios. Lastly, our data show a weak relationship between
      parental investment and the ASR that depends on social class. We discuss these
      results in the light of recent reformulations of parental investment theory.This
      article is part of the themed issue 'Adult sex ratios and reproductive decisions:
      a critical re-examination of sex differences in human and animal societies'.

PMID- 28760763
TI  - Adult sex ratios and their implications for cooperative breeding in birds.
AB  - Cooperative breeding is a form of breeding system where in addition to a core
      breeding pair, one or more usually non-breeding individuals provide offspring
      care. Cooperative breeding is widespread in birds, but its origin and maintenance
      in contemporary populations are debated. Although deviations in adult sex ratio
      (ASR, the proportion of males in the adult population) have been hypothesized to
      influence the occurrence of cooperative breeding because of the resulting surplus
      of one sex and limited availability of breeding partners, this hypothesis has not
      been tested across a wide range of taxa. By using data from 188 bird species and
      phylogenetically controlled analyses, we show that cooperatively breeding species
      have more male-biased ASRs than non-cooperative species. Importantly, ASR
      predicts helper sex ratio: in species with more male-biased ASR, helper sex ratio
      is also more male biased. We also show that offspring sex ratios do not predict
      ASRs, so that the skewed ASRs emerge during the period when individuals aim to
      obtain a breeding position or later during adulthood. In line with this result,
      we found that ASR (among both cooperatively and non-cooperatively breeding
      species) is inversely related to sex bias in dispersal distance, suggesting that
      the cost of dispersal is more severe for the further-dispersing sex. As females
      usually disperse further in birds, this explains the generally male-biased ASR,
      and in combination with benefits of philopatry for males, this probably explains
      why ASR is more biased in cooperatively breeding species. Taken together, our
      results suggest that a sex bias in helping in cooperatively breeding species
      relates to biased ASRs. We propose that this relationship is driven by sex
      specific costs and benefits of dispersal and helping, as well as other
      demographic factors. Future phylogenetic comparative and experimental work is
      needed to establish how this relationship emerges.This article is part of the
      themed issue 'Adult sex ratios and reproductive decisions: a critical re
      examination of sex differences in human and animal societies'.

PMID- 28760762
TI  - Sex roles and adult sex ratios: insights from mammalian biology and consequences
      for primate behaviour.
AB  - Theoretical models and empirical studies in various taxa have identified
      important links between variation in sex roles and the number of adult males and
      females (adult sex ratio (ASR)) in a population. In this review, I examine these
      relationships in non-human primates. Because most existing theoretical models of
      the evolution of sex roles focus on the evolutionary origins of sex-biased
      behaviour, they offer only a general scaffold for predicting variation in sex
      roles among and within species. I argue that studies examining sex role variation
      at these more specific levels need to take social organization into account to
      identify meaningful levels for the measurement of ASR and to account for the fact
      that ASR and sex roles mutually influence each other. Moreover, taxon-specific
      life-history traits can constrain sex role flexibility and impact the operational
      sex ratio (OSR) by specifying the minimum length of female time outs from
      reproduction. Using examples from the primate literature, I highlight practical
      problems in estimating ASR and OSR. I then argue that interspecific variation in
      the occurrence of indirect forms of paternal care might indeed be linked to
      variation in ASR. Some studies also indicate that female aggression and bonding,
      as well as components of inter-sexual relationships, are sensitive to variation
      in ASR. Thus, links between primate sex roles and sex ratios merit further study,
      and such studies could prompt the development of more specific theoretical models
      that make realistic assumptions about taxon-specific life history and social
      organization.This article is part of the themed issue 'Adult sex ratios and
      reproductive decisions: a critical re-examination of sex differences in human and
      animal societies'.

PMID- 28760764
TI  - Social determinants of adult sex ratios and racial/ethnic disparities in
      transmission of HIV and other sexually transmitted infections in the USA.
AB  - In Black population centres in the USA, adult sex ratios (ASRs) are strongly
      female-biased primarily due to high male incarceration and early mortality rates.
      I explore the system of social determinants that shape these ASRs, and describe
      their apparent consequences. Evidence suggests that female-biased ASRs play a
      role, along with racial residential segregation, to increase mixing between core
      and peripheral members of sexual networks, facilitating transmission of human
      immunodeficiency virus and other sexually transmitted infections. Unique
      historical factors underlie Black male incarceration and mortality rates in the
      USA, making comparisons with other groups or other countries challenging.This
      article is part of the themed issue 'Adult sex ratios and reproductive decisions:
      a critical re-examination of sex differences in human and animal societies'.

PMID- 28760765
TI  - High sex ratios in rural China: declining well-being with age in never-married
      men.
AB  - In parts of rural China male-biased sex ratios at birth, combined with out
      migration of women, have led to highly male-biased adult sex ratios, resulting in
      large numbers of men being unable to marry, in a culture where marriage and
      reproduction are an expectation. The aim of this study was to test the hypotheses
      that older unmarried men are more predisposed to depression, low self-esteem and
      aggression than both those who are married, and those who are younger and
      unmarried. Self-completion questionnaires were administered among men aged 20-40
      in 48 villages in rural Guizhou province, southwestern China. Tools used included
      the Beck Depression Inventory, the Rosenberg's Self-esteem Scale and the Bryant
      Smith Aggression Questionnaire. Regression models assessed psychological
      wellbeing while adjusting for socio-demographic variables. Completed
      questionnaires were obtained from 957 never-married men, 535 married men aged 30
      40, 394 partnered men and 382 unpartnered men aged 20-29. After adjusting for
      socio-demographic variables, never-married men were more predisposed to
      depression (p < 0.05), aggression (p < 0.01), low self-esteem (p < 0.05) and
      suicidal tendencies (p < 0.001). All the psychological measures deteriorated with
      age in never-married men. In contrast, married men remained stable on these
      dimensions with age. Never-married men are a psychologically highly vulnerable
      group in a society where marriage is an expectation. Since the highest birth sex
      ratio cohorts have not yet reached reproductive age, the social tragedy of these
      men will last for at least another generation.This article is part of the themed
      issue 'Adult sex ratios and reproductive decisions: a critical re-examination of
      sex differences in human and animal societies'.

PMID- 28760766
TI  - Climate-driven shifts in adult sex ratios via sex reversals: the type of sex
      determination matters.
AB  - Sex reversals whereby individuals of one genetic sex develop the phenotype of the
      opposite sex occur in ectothermic vertebrates with genetic sex-determination
      systems that are sensitive to extreme temperatures during sexual differentiation.
      Recent rises in global temperatures have led researchers to predict that sex
      reversals will become more common, resulting in the distortion of many
      populations' sex ratios. However, it is unclear whether susceptibility to climate
      driven sex-ratio shifts depends on the type of sex determination that varies
      across species. First, we show here using individual-based theoretical models
      that XX/XY (male-heterogametic) and ZZ/ZW (female-heterogametic) sex
      determination systems can respond differentially to temperature-induced sex
      reversals. Interestingly, the impacts of climate warming on adult sex ratio (ASR)
      depend on the effects of both genotypic and phenotypic sex on survival and
      reproduction. Second, we analyse the temporal changes of ASR in natural amphibian
      populations using data from the literature, and find that ASR shifted towards
      males in ZZ/ZW species over the past 60 years, but did not change significantly
      in XX/XY species. Our results highlight the fact that we need a better
      understanding of the interactions between genetic and environmental sex
      determining mechanisms to predict the responses of ectotherms to climate change
      and the associated extinction risks.This article is part of the themed issue
      'Adult sex ratios and reproductive decisions: a critical re-examination of sex
      differences in human and animal societies'.

PMID- 28760767
TI  - Demographic and genetic consequences of disturbed sex determination.
AB  - During sex determination, genetic and/or environmental factors determine the
      cascade of processes of gonad development. Many organisms, therefore, have a
      developmental window in which their sex determination can be sensitive to, for
      example, unusual temperatures or chemical pollutants. Disturbed environments can
      distort population sex ratios and may even cause sex reversal in species with
      genetic sex determination. The resulting genotype-phenotype mismatches can have
      long-lasting effects on population demography and genetics. I review the
      theoretical and empirical work in this context and explore in a simple population
      model the role of the fitness vyy of chromosomally aberrant YY genotypes that are
      a consequence of environmentally induced feminization. Low vyy is mostly
      beneficial for population growth. During feminization, low vyy reduces the
      proportion of genetic males and hence accelerates population growth, especially
      at low rates of feminization and at high fitness costs of the feminization itself
      (i.e. when feminization would otherwise not affect population dynamics much).
      When sex reversal ceases, low vyy mitigates the negative effects of feminization
      and can even prevent population extinction. Little is known about vyy in natural
      populations. The available models now need to be parametrized in order to better
      predict the long-term consequences of disturbed sex determination.This article is
      part of the themed issue 'Adult sex ratios and reproductive decisions: a critical
      re-examination of sex differences in human and animal societies'.

PMID- 28760768
TI  - Evolution of male strategies with sex-ratio-dependent pay-offs: connecting pair
      bonds with grandmothering.
AB  - Men's provisioning of mates and offspring has been central to ideas about human
      evolution because paternal provisioning is absent in our closest evolutionary
      cousins, the great apes, and is widely assumed to result in pair bonding, which
      distinguishes us from them. Yet mathematical modelling has shown that paternal
      care does not readily spread in populations where competition for multiple mates
      is the common male strategy. Here we add to models that point to the mating sex
      ratio as an explanation for pairing as pay-offs to mate guarding rise with a male
      biased sex ratio. This is of interest for human evolution because our
      grandmothering life history shifts the mating sex ratio from female- to male
      biased. Using a difference equation model, we explore the relative pay-offs for
      three competing male strategies (dependant care, multiple mating, mate guarding)
      in response to changing adult sex ratios. When fertile females are abundant,
      multiple mating prevails. As they become scarce, mate guarding triumphs. The
      threshold for this shift depends on guarding efficiency. Combined with mating sex
      ratios of hunter-gatherer and chimpanzee populations, these results strengthen
      the hypothesis that the evolution of our grandmothering life history propelled
      the shift to pair bonding in the human lineage.This article is part of the themed
      issue 'Adult sex ratios and reproductive decisions: a critical re-examination of
      sex differences in human and animal societies'.

PMID- 28760770
TI  - Transcriptional mechanisms that control expression of the macrophage colony
      stimulating factor receptor locus.
AB  - The proliferation, differentiation, and survival of cells of the macrophage
      lineage depends upon signals from the macrophage colony-stimulating factor (CSF)
      receptor (CSF1R). CSF1R is expressed by embryonic macrophages and induced early
      in adult hematopoiesis, upon commitment of multipotent progenitors to the myeloid
      lineage. Transcriptional activation of CSF1R requires interaction between members
      of the E26 transformation-specific family of transcription factors (Ets) (notably
      PU.1), C/EBP, RUNX, AP-1/ATF, interferon regulatory factor (IRF), STAT, KLF, REL,
      FUS/TLS (fused in sarcoma/ranslocated in liposarcoma) families, and conserved
      regulatory elements within the mouse and human CSF1R locus. One element, the Fms
      intronic regulatory element (FIRE), within intron 2, is conserved functionally
      across all the amniotes. Lineage commitment in multipotent progenitors also
      requires down-regulation of specific transcription factors such as MYB, FLI1,
      basic leucine zipper transcriptional factor ATF-like (BATF3), GATA-1, and PAX5
      that contribute to differentiation of alternative lineages and repress CSF1R
      transcription. Many of these transcription factors regulate each other, interact
      at the protein level, and are themselves downstream targets of CSF1R signaling.
      Control of CSF1R transcription involves feed-forward and feedback signaling in
      which CSF1R is both a target and a participant; and dysregulation of CSF1R
      expression and/or function is associated with numerous pathological conditions.
      In this review, we describe the regulatory network behind CSF1R expression during
      differentiation and development of cells of the mononuclear phagocyte system.

PMID- 28760769
TI  - Filopodyan: An open-source pipeline for the analysis of filopodia.
AB  - Filopodia have important sensory and mechanical roles in motile cells. The
      recruitment of actin regulators, such as ENA/VASP proteins, to sites of
      protrusion underlies diverse molecular mechanisms of filopodia formation and
      extension. We developed Filopodyan (filopodia dynamics analysis) in Fiji and R to
      measure fluorescence in filopodia and at their tips and bases concurrently with
      their morphological and dynamic properties. Filopodyan supports high-throughput
      phenotype characterization as well as detailed interactive editing of filopodia
      reconstructions through an intuitive graphical user interface. Our highly
      customizable pipeline is widely applicable, capable of detecting filopodia in
      four different cell types in vitro and in vivo. We use Filopodyan to quantify the
      recruitment of ENA and VASP preceding filopodia formation in neuronal growth
      cones, and uncover a molecular heterogeneity whereby different filopodia display
      markedly different responses to changes in the accumulation of ENA and VASP
      fluorescence in their tips over time.

PMID- 28760772
TI  - Correction: Identifying factors that lead to the persistence of imported
      gonorrhoeae strains: a modelling study.

PMID- 28760771
TI  - Diabetic nephropathy - is this an immune disorder?
AB  - Chronic diabetes is associated with metabolic and haemodynamic stresses which can
      facilitate modifications to DNA, proteins and lipids, induce cellular dysfunction
      and damage, and stimulate inflammatory and fibrotic responses which lead to
      various types of renal injury. Approximately 30-40% of patients with diabetes
      develop nephropathy and this renal injury normally progresses in about a third of
      patients. Due to the growing incidence of diabetes, diabetic nephropathy is now
      the main cause of end-stage renal disease (ESRD) worldwide. Accumulating evidence
      from experimental and clinical studies has demonstrated that renal inflammation
      plays a critical role in determining whether renal injury progresses during
      diabetes. However, the immune response associated with diabetic nephropathy is
      considerably different to that seen in autoimmune kidney diseases or in acute
      kidney injury arising from episodes of ischaemia or infection. This review
      evaluates the role of the immune system in the development of diabetic
      nephropathy, including the specific contributions of leucocyte subsets
      (macrophages, neutrophils, mast cells, T and B lymphocytes), danger-associated
      molecular patterns (DAMPs), inflammasomes, immunoglobulin and complement. It also
      examines factors which may influence the development of the immune response,
      including genetic factors and exposure to other kidney insults. In addition, this
      review discusses therapies which are currently under development for targeting
      the immune system in diabetic nephropathy and indicates those which have
      proceeded into clinical trials.

PMID- 28760773
TI  - Alternative Lengthening of Telomeres Mediated by Mitotic DNA Synthesis Engages
      Break-Induced Replication Processes.
AB  - Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere
      maintenance mechanism that occurs in a subset of cancers. By analyzing telomerase
      positive cells and their human TERC knockout-derived ALT human cell lines, we
      show that ALT cells harbor more fragile telomeres representing telomere
      replication problems. ALT-associated replication defects trigger mitotic DNA
      synthesis (MiDAS) at telomeres in a RAD52-dependent, but RAD51-independent,
      manner. Telomeric MiDAS is a conservative DNA synthesis process, potentially
      mediated by break-induced replication, similar to type II ALT survivors in
      Saccharomyces cerevisiae Replication stresses induced by ectopic oncogenic
      expression of cyclin E, G-quadruplexes, or R-loop formation facilitate the ALT
      pathway and lead to telomere clustering, a hallmark of ALT cancers. The
      TIMELESS/TIPIN complex suppresses telomere clustering and telomeric MiDAS,
      whereas the SMC5/6 complex promotes them. In summary, ALT cells exhibit more
      telomere replication defects that result in persistent DNA damage responses at
      telomeres, leading to the engagement of telomeric MiDAS (spontaneous mitotic
      telomere synthesis) that is triggered by DNA replication stress, a potential
      driver of genomic duplications in cancer.

PMID- 28760774
TI  - Unperturbed Immune Function despite Mutation of C-Terminal Tyrosines in Syk
      Previously Implicated in Signaling and Activity Regulation.
AB  - The nonreceptor tyrosine kinase Syk, a central regulator of immune cell
      differentiation and activation, is a promising drug target for treatment of
      leukemia and allergic and inflammatory diseases. The clinical failure of Syk
      inhibitors underscores the importance of understanding the regulation of Syk
      function and activity. A series of previous studies emphasized the importance of
      three C-terminal tyrosines in Syk for kinase activity regulation, as docking
      sites for downstream effector molecules, and for Ca2+ mobilization. Here, we
      investigated the roles of these C-terminal tyrosines in the mouse. Surprisingly,
      expression of a triple tyrosine-to-phenylalanine human Syk mutant, SYK(Y3F), was
      not associated with discernible signaling defects either in reconstituted DT40
      cells or in B or mast cells from mice expressing SYK(Y3F) instead of wild-type
      Syk. Remarkably, lymphocyte differentiation, calcium mobilization, and 2,4,6
      trinitrophenyl (TNP)-specific immune responses were unperturbed in SYK(Y3F) mice.
      These results emphasize the capacity of immune cells to compensate for specific
      molecular defects, likely using redundant intermolecular interactions, and
      highlight the importance of in vivo analyses for understanding cellular signaling
      mechanisms.

PMID- 28760775
TI  - PARN Modulates Y RNA Stability and Its 3'-End Formation.
AB  - Loss-of-function mutations in 3'-to-5' exoribonucleases have been implicated in
      hereditary human diseases. For example, PARN mutations cause a severe form of
      dyskeratosis congenita (DC), wherein PARN deficiency leads to human telomerase
      RNA instability. Since the DC phenotype in PARN patients is even more severe than
      that of loss-of-function alleles in telomerase components, we hypothesized that
      PARN would also be required for the stability of other RNAs. Here, we show that
      PARN depletion reduces the levels of abundant human Y RNAs, which might
      contribute to the severe phenotype of DC observed in patients. Depletion of PAPD5
      or the cytoplasmic exonuclease DIS3L rescues the effect of PARN depletion on Y
      RNA levels, suggesting that PARN stabilizes Y RNAs by removing oligoadenylated
      tails added by PAPD5, which would otherwise recruit DIS3L for Y RNA degradation.
      Through deep sequencing of 3' ends, we provide evidence that PARN can also
      deadenylate the U6 and RMRP RNAs without affecting their levels. Moreover, we
      observed widespread posttranscriptional oligoadenylation, uridylation, and
      guanylation of U6 and Y RNA 3' ends, suggesting that in mammalian cells, the
      formation of a 3' end for noncoding RNAs can be a complex process governed by the
      activities of various 3'-end polymerases and exonucleases.

PMID- 28760776
TI  - TIE2 Associates with Caveolae and Regulates Caveolin-1 To Promote Their Nuclear
      Translocation.
AB  - DNA repair pathways are aberrant in cancer, enabling tumor cells to survive
      standard therapies-chemotherapy and radiotherapy. Our group previously reported
      that, upon irradiation, the membrane-bound tyrosine kinase receptor TIE2
      translocates into the nucleus and phosphorylates histone H4 at Tyr51, recruiting
      ABL1 to the DNA repair complexes that participate in the nonhomologous end
      joining pathway. However, no specific molecular mechanisms of TIE2 endocytosis
      have been reported. Here, we show that irradiation or ligand-induced TIE2
      trafficking is dependent on caveolin-1, the main component of caveolae.
      Subcellular fractionation and confocal microscopy demonstrated TIE2/caveolin-1
      complexes in the nucleus, and using inhibitor or small interfering RNAs (siRNAs)
      against caveolin-1 or Tie2 inhibited their trafficking. TIE2 was found in
      caveolae and directly phosphorylated caveolin-1 at Tyr14 in vitro and in vivo
      This modification regulated the generation of TIE2/caveolin-1 complexes and was
      essential for TIE2/caveolin-1 nuclear translocation. Our data further demonstrate
      that the combination of TIE2 and caveolin-1 inhibitors resulted in significant
      radiosensitization of malignant glioma cells, which will guide the development of
      combinatorial treatment with radiotherapy for patients with glioblastoma.

PMID- 28760778
TI  - Letter by Garcia-Moll Regarding Article, "Glycemic Control Status After
      Percutaneous Coronary Intervention and Long-Term Clinical Outcomes in Patients
      With Type 2 Diabetes Mellitus".

PMID- 28760777
TI  - SUMOylation Negatively Regulates Angiogenesis by Targeting Endothelial NOTCH
      Signaling.
AB  - RATIONALE: The highly conserved NOTCH (neurogenic locus notch homolog protein)
      signaling pathway functions as a key cell-cell interaction mechanism controlling
      cell fate and tissue patterning, whereas its dysregulation is implicated in a
      variety of developmental disorders and cancers. The pivotal role of endothelial
      NOTCH in regulation of angiogenesis is widely appreciated; however, little is
      known about what controls its signal transduction. Our previous study indicated
      the potential role of post-translational SUMO (small ubiquitin-like modifier)
      modification (SUMOylation) in vascular disorders. OBJECTIVE: The aim of this
      study was to investigate the role of SUMOylation in endothelial NOTCH signaling
      and angiogenesis. METHODS AND RESULTS: Endothelial SENP1 (sentrin-specific
      protease 1) deletion, in newly generated endothelial SENP1 (the major protease of
      the SUMO system)-deficient mice, significantly delayed retinal vascularization by
      maintaining prolonged NOTCH1 signaling, as confirmed in cultured endothelial
      cells. An in vitro SUMOylation assay and immunoprecipitation revealed that when
      SENP1 associated with N1ICD (NOTCH1 intracellular domain), it functions as a
      deSUMOylase of N1ICD SUMOylation on conserved lysines. Immunoblot and
      immunoprecipitation analyses and dual-luciferase assays of natural and SUMO
      conjugated/nonconjugated NOTCH1 forms demonstrated that SUMO conjugation
      facilitated NOTCH1 cleavage. This released N1ICD from the membrane and stabilized
      it for translocation to the nucleus where it functions as a cotranscriptional
      factor. Functionally, SENP1-mediated NOTCH1 deSUMOylation was required for NOTCH
      signal activation in response to DLL4 (Delta-like 4) stimulation. This in turn
      suppressed VEGF (vascular endothelial growth factor) receptor signaling and
      angiogenesis, as evidenced by immunoblotted signaling molecules and in vitro
      angiogenesis assays. CONCLUSIONS: These results establish reversible NOTCH1
      SUMOylation as a regulatory mechanism in coordinating endothelial angiogenic
      signaling; SENP1 acts as a critical intrinsic mediator of this process. These
      findings may apply to NOTCH-regulated biological events in nonvascular tissues
      and provide a novel therapeutic strategy for vascular diseases and tumors.

PMID- 28760779
TI  - Response by Hwang et al to Letter Regarding Article, "Glycemic Control Status
      After Percutaneous Coronary Intervention and Long-Term Clinical Outcomes in
      Patients With Type 2 Diabetes Mellitus".

PMID- 28760781
TI  - miR-432 Induces NRF2 Stabilization by Directly Targeting KEAP1.
AB  - NF-E2-related factor 2 (NRF2) is a master transcriptional regulator that
      integrates cellular stress responses and is negatively regulated by Kelch-like
      ECH-associated protein 1 (KEAP1) at the post-translational level. In human
      cancers, aberrantly stabilized NRF2, by the mutation of either NRF2 or KEAP1 or
      by the potential inhibition of autophagy, plays a vital role in tumor growth and
      chemoresistance through the activation of target genes. MicroRNAs (miRNA) are
      endogenous small noncoding RNAs that can negatively regulate gene expression by
      interfering with translation and/or stability of target transcripts. However,
      miRNA-mediated regulation of the NRF2-KEAP1 pathway under physiological
      conditions is poorly understood. Here, miR-432-3p positively regulates NRF2
      activity through the downregulation of KEAP1 by a direct-binding mechanism to the
      coding region of KEAP1. Overexpression of miR-432-3p resulted in a decreased
      sensitivity of esophageal squamous cell carcinoma (ESCC) cells to chemotherapy
      drugs including cisplatin (CDDP). Conversely, the inhibition of miR-432-3p
      expression by the CRISPR/Cas9 system resulted in an increased sensitivity of ESCC
      cells to CDDP. Furthermore, miR-432-3p was overexpressed in primary ESCC tumors
      (55 of 84, 65.5%) and a negative correlation between the expression level of
      KEAP1 and miR-432-3p in primary ESCC tumors was observed.Implications: These
      findings provide novel insights into the mechanism of NRF2 stabilization in human
      cancers. Mol Cancer Res; 15(11); 1570-8. (c)2017 AACR.

PMID- 28760780
TI  - Structural Determinants for the Selectivity of the Positive KCa3.1 Gating
      Modulator 5-Methylnaphtho[2,1-d]oxazol-2-amine (SKA-121).
AB  - Intermediate-conductance (KCa3.1) and small-conductance (KCa2) calcium-activated
      K+ channels are gated by calcium binding to calmodulin (CaM) molecules associated
      with the calmodulin-binding domain (CaM-BD) of these channels. The existing KCa
      activators, such as naphtho[1,2-d]thiazol-2-ylamine (SKA-31), 6,7-dichloro-1H
      indole-2,3-dione 3-oxime (NS309), and 1-ethylbenzimidazolin-2-one (EBIO),
      activate both channel types with similar potencies. In a previous chemistry
      effort, we optimized the benzothiazole pharmacophore of SKA-31 toward KCa3.1
      selectivity and identified 5-methylnaphtho[2,1-d]oxazol-2-amine (SKA-121), which
      exhibits 40-fold selectivity for KCa3.1 over KCa2.3. To understand why
      introduction of a single CH3 group in five-position of the benzothiazole/oxazole
      system could achieve such a gain in selectivity for KCa3.1 over KCa2.3, we first
      localized the binding site of the benzothiazoles/oxazoles to the CaM-BD/CaM
      interface and then used computational modeling software to generate models of the
      KCa3.1 and KCa2.3 CaM-BD/CaM complexes with SKA-121. Based on a combination of
      mutagenesis and structural modeling, we suggest that all benzothiazole/oxazole
      type KCa activators bind relatively "deep" in the CaM-BD/CaM interface and
      hydrogen bond with E54 on CaM. In KCa3.1, SKA-121 forms an additional hydrogen
      bond network with R362. In contrast, NS309 sits more "forward" and directly
      hydrogen bonds with R362 in KCa3.1. Mutating R362 to serine, the corresponding
      residue in KCa2.3 reduces the potency of SKA-121 by 7-fold, suggesting that R362
      is responsible for the generally greater potency of KCa activators on KCa3.1. The
      increase in SKA-121's KCa3.1 selectivity compared with its parent, SKA-31, seems
      to be due to better overall shape complementarity and hydrophobic interactions
      with S372 and M368 on KCa3.1 and M72 on CaM at the KCa3.1-CaM-BD/CaM interface.

PMID- 28760782
TI  - CDK4/6 Inhibition on Glucose and Pancreatic Beta Cell Homeostasis in Young and
      Aged Rats.
AB  - Genetic deletion of cyclin-dependent kinase 4 (Cdk4) is associated with
      pancreatic beta cell loss and glucose dysregulation in rodents. Palbociclib, one
      of the first selective CDK4/6 inhibitors approved for the treatment of advanced
      breast cancer, is currently being investigated as an adjuvant treatment in
      patients with early-stage breast cancer and in a variety of cancers covering a
      wide-range of patient populations. Hence, longer chronic toxicity studies were
      necessary to further examine its safety profile. The effects of different doses
      and duration of palbociclib administration on glucose and beta cell homeostasis
      in young (two months) versus aged (12 months) rats was compared. Glucose
      dysregulation, due to pancreatic beta cell degeneration, was observed in young
      rats administered the highest dose of palbociclib for 6 months. Abnormal
      pancreatic islet histology and activation of the endoplasmic reticulum stress
      response in beta cells were detected after shorter administration with high-dose
      palbociclib in young rats. To test the hypothesis that palbociclib-associated
      inhibition of beta cell proliferation will more profoundly affect younger animals
      that have not achieved replicative quiescence, we administered high-dose
      palbociclib to aged rats for 6 months. In contrast to the young rats, despite
      equivalent exposures to palbociclib, no evidence of impaired glucose tolerance,
      hypoinsulinemia, beta cell vacuolization, or beta cell loss was seen in aged
      rats. Palbociclib administration induces beta cell failure in young but not aged
      rats.Implications: Although adult humans receiving palbociclib have not displayed
      detectable adverse effects on glucose metabolism, the risk of beta cell failure
      in children remains unexplored. Mol Cancer Res; 15(11); 1531-41. (c)2017 AACR.

PMID- 28760783
TI  - Infographic. Golf spectating and health.

PMID- 28760784
TI  - Tablet technology in medical education in South Africa: a mixed methods study.
AB  - OBJECTIVE: The purpose of this study was to establish the use of mobile devices
      by learners at a selected medical school. Distribution of mobile devices was an
      inaugural initiative implemented by our college. DESIGN: A mixed methodology
      design using a questionnaire comprising both open-ended and close-ended questions
      was analysed from 179 (60 male; 119 female) second year medical students
      registered for the Anatomy course. Open-ended questions were analysed using a
      thematic approach by identifying emergent ideas and concepts. Close-ended
      questions were analysed using SPSS V.21.0. SETTING AND PARTICIPANTS: Second year
      medical students at a medical school in South Africa. RESULTS: Three main themes
      emerged, namely, (a) mobile device engagement, (b) advantages and (c) challenges
      affecting use of mobile devices. A majority of learners accessed their tablets
      for lecture notes; more females were inclined to access these devices than males.
      Challenges experienced included poor wifi connectivity on and off the university
      campus; some students were not keen on the idea of mobile devices and preferred
      traditional methods of teaching. CONCLUSIONS: Mobile devices have been adopted by
      learners at our university. Uses of technology outlined are related to Eraut's
      intentions of informal learning. Integrating tablets into classes had a positive
      effect on student access to course material.

PMID- 28760785
TI  - Food insecurity and maternal-child nutritional status in Mexico: cross-sectional
      analysis of the National Health and Nutrition Survey 2012.
AB  - OBJECTIVE: To examine the association between household food insecurity (HFI) and
      risk of childhood stunting and to determine whether this association is modified
      by maternal-child overweight/obesity. DESIGN: Observational cross-sectional
      study. SETTING: Data come from the Mexican National Health and Nutrition Survey
      (ENSANUT 2012 by its initials in Spanish), representative of rural and urban
      areas. PARTICIPANTS: Our study sample included 5087 mother-preschool child pairs
      and 7181 mother-schoolchild pairs. MAIN OUTCOME MEASURES: Differences in the
      prevalence (95% CI) of each HFI category by socioeconomic characteristics and
      maternal-child nutritional status were estimated. A logistic regression model was
      conducted for stunting and overweight among preschool children and for stunting
      and overweight/obesity among schoolchildren, adjusting for pertinent covariates.
      HFI was measured according to the Latin American and Caribbean Food Security
      Scale (ELCSA by its initials in Spanish). Weight and recumbent lenght or height
      measures were obtained from children. Overweight and obesity in women were
      determined according to the WHO Growth Reference Charts. The following covariates
      were included: sex of the child. urbanicity (urban/rural), region of residence
      and maternal education. Benefiting from food assistance programmes and
      socioeconomic status index were also included. Results were expressed as adjusted
      ORs. RESULTS: Stunting proved more prevalent in preschool children with moderate
      or severe HFI (16.2% and 16.8%, respectively) (p=0.036 and p=0.007, respectively)
      than in their counterparts with mild or no HFI (13.2% and 10.7%, respectively).
      Furthermore, the interaction between HFI and maternal obesity had a significant
      impact on stunting in preschool children (p<0.05). Severe HFI increased risk of
      stunting in children with non-obese mothers but not in those with obese mothers.
      CONCLUSION: We have discovered a new relationship between HFI and maternal
      obesity on the one hand and risk of childhood stunting on the other hand. This
      may reflect a shared mechanism involving dual forms of malnutrition.

PMID- 28760786
TI  - How are age-related differences in sleep quality associated with health outcomes?
      An epidemiological investigation in a UK cohort of 2406 adults.
AB  - OBJECTIVES: To examine age-related differences in self-reported sleep quality and
      their associations with health outcomes across four domains: physical health,
      cognitive health, mental health and neural health. SETTING: Cambridge Centre for
      Ageing and Neuroscience (Cam-CAN) is a cohort study in East Anglia/England, which
      collected self-reported health and lifestyle questions as well as a range of
      objective measures from healthy adults. PARTICIPANTS: 2406 healthy adults (age 18
      98) answered questions about their sleep quality (Pittsburgh Sleep Quality Index
      (PSQI)) and measures of physical, cognitive, mental and neural health. A subset
      of 641 individuals provided measures of brain structure. MAIN OUTCOME MEASURES:
      PSQI scores of sleep and scores across tests within the four domains of health.
      Latent class analysis (LCA) is used to identify sleep types across the lifespan.
      Bayesian regressions quantify the presence, and absence, of relationships between
      sleep quality and health measures. RESULTS: Better self-reported sleep is
      generally associated with better health outcomes, strongly so for mental health,
      moderately for cognitive and physical health, but not for sleep quality and
      neural health. LCA identified four sleep types: 'good sleepers' (68.1%, most
      frequent in middle age), 'inefficient sleepers' (14.01%, most frequent in old
      age), 'delayed sleepers' (9.28%, most frequent in young adults) and 'poor
      sleepers' (8.5%, most frequent in old age). There is little evidence for
      interactions between sleep quality and age on health outcomes. Finally, we
      observe U-shaped associations between sleep duration and mental health
      (depression and anxiety) as well as self-reported general health, such that both
      short and long sleep were associated with poorer outcomes. CONCLUSIONS: Lifespan
      changes in sleep quality are multifaceted and not captured well by summary
      measures, but instead should be viewed as as partially independent symptoms that
      vary in prevalence across the lifespan. Better self-reported sleep is associated
      with better health outcomes, and the strength of these associations differs
      across health domains. Notably, we do not observe associations between self
      reported sleep quality and white matter.

PMID- 28760788
TI  - Childhood hospitalisation and related deaths in Hanoi, Vietnam: a tertiary
      hospital database analysis from 2007 to 2014.
AB  - OBJECTIVE: To describe hospital admission and emergency visit rates and potential
      risk factors of prolonged hospitalisation and death among children in Hanoi.
      STUDY DESIGN: A retrospective study reviewed 212 216 hospitalisation records of
      children (aged 0-17) who attended the Vietnam National Children's Hospital in
      Hanoi between 2007 and 2014. Four indicators were analysed and reported: (1) rate
      of emergency hospital visits, (2) rate of hospitalisation, (3) length of hospital
      stay and (4) number of deaths. The risk of prolonged hospitalisation was
      investigated using Cox proportion hazard, and the risk of death was investigated
      through logistic regressions. RESULTS: During 2007-2014, the average annual rate
      of emergency visits was 2.2 per 1000 children and the rate of hospital admissions
      was 13.8 per 1000 children. The annual rates for infants increased significantly
      by 3.9 per 1000 children during 2012-2014 for emergency visits and 25.1 per 1000
      children during 2009-2014 for hospital admissions. Digestive diseases (32.0%) and
      injuries (30.2%) were common causes of emergency visits, whereas respiratory
      diseases (37.7%) and bacterial and parasitic infections (19.8%) accounted for
      most hospital admissions. Patients with mental and behavioural disorders remained
      in the hospital the longest (median=12 days). Morbidities related to the
      perinatal period dominated mortality causes (32.5% of deaths among those admitted
      to the hospital. Among the respiratory diseases, pneumonia was the leading cause
      of both prolonged hospitalisation and death. CONCLUSIONS: Preventable health
      problems, such as common bacterial infections and respiratory diseases, were the
      primary causes of hospital admissions in Vietnam.

PMID- 28760787
TI  - Bridging the age gap in breast cancer: evaluation of decision support
      interventions for older women with operable breast cancer: protocol for a cluster
      randomised controlled trial.
AB  - INTRODUCTION: While breast cancer outcomes are improving steadily in younger
      women due to advances in screening and improved therapies, there has been little
      change in outcomes among the older age group. It is inevitable that
      comorbidities/frailty rates are higher, which may increase the risks of some
      breast cancer treatments such as surgery and chemotherapy, many older women are
      healthy and may benefit from their use. Adjusting treatment regimens
      appropriately for age/comorbidity/frailty is variable and largely non-evidence
      based, specifically with regard to rates of surgery for operable oestrogen
      receptor-positive disease and rates of chemotherapy for high-risk disease.
      METHODS AND ANALYSIS: This multicentre, parallel group, pragmatic cluster
      randomised controlled trial (RCT) (2015-18) reported here is nested within a
      larger ongoing 'Age Gap Cohort Study' (2012-18RP-PG-1209-10071), aims to evaluate
      the effectiveness of a complex intervention of decision support interventions to
      assist in the treatment decision making for early breast cancer in older women.
      The interventions include two patient decision aids (primary endocrine therapy vs
      surgery/antioestrogen therapy and chemotherapy vs no chemotherapy) and a clinical
      treatment outcomes algorithm for clinicians. ETHICS AND DISSEMINATION: National
      and local ethics committee approval was obtained for all UK participating sites.
      Results from the trial will be submitted for publication in international peer
      reviewed scientific journals. IRAS REFERENCE: 115550. TRIAL REGISTRATION NUMBER:
      European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2015
      004220-61;Pre-results. Sponsor's Protocol Code Number Sheffield Teaching
      Hospitals STH17086. ISRCTN 32447*.

PMID- 28760789
TI  - Guidelines for the symptomatic management of fever in children: systematic review
      of the literature and quality appraisal with AGREE II.
AB  - INTRODUCTION: Several societies have produced and disseminated clinical practice
      guidelines (CPGs) for the symptomatic management of fever in children. However,
      to date, the quality of such guidelines has not been appraised. OBJECTIVE: To
      identify and evaluate guidelines for the symptomatic management of fever in
      children. METHODS: The research was conducted using PubMed, guideline websites,
      and Google (January 2010 to July 2016). The quality of the CPGs was independently
      assessed by two assessors using the Appraisal of Guidelines for Research &
      Evaluation II (AGREE II) instrument, and specific recommendations in guidelines
      were summarised and evaluated. Domain scores were considered of sufficient
      quality when >60% and of good quality when >80%. RESULTS: Seven guidelines were
      retrieved. The median score for the scope and purpose domain was 85.3% (range
      66.6-100%). The median score for the stakeholder involvement domain was 57.5%
      (range 33.3-83.3%) and four guidelines scored >60%. The median score for the
      rigour of development domain was 52.0% (range 14.6-98.9%), and only three
      guidelines scored >60%. The median score for the clarity of presentation domain
      was 80.9% (range 50.0-94.4%). The median score for the applicability domain was
      39.3% (8.3-100%). Only one guideline scored >60%. The median score for the
      editorial independence domain was 48.84% (0-91.6%); only three guidelines scored
      >60%. CONCLUSION: Most guidelines were recommended for use even if with
      modification, especially in the methodology, the applicability and the editorial
      independence domains. Our results could help improve reporting of future
      guidelines, and affect the selection and use of guidelines in clinical practice.

PMID- 28760790
TI  - Impact of health insurance coverage for Helicobacter pylori gastritis on the
      trends in eradication therapy in Japan: retrospective observational study and
      simulation study based on real-world data.
AB  - OBJECTIVES: To explore the prevalence of Helicobacter pylori infection in Japan
      and the trends of its eradication therapy before and after the changes of the
      insurance coverage policy, first started in 2000, and expanded to cover H. pylori
      positive gastritis in 2013. The impacts that the changes brought were estimated.
      METHODS: In this retrospective observational study and simulation study based on
      health insurance claims data, product sales data and relevant studies,
      individuals who received triple therapy (amoxicillin, clarithromycin, proton-pump
      inhibitors or potassium-competitive acid blockers) were defined as the first-time
      patients for H. pylori eradication in two Japanese health insurance claims
      databases (from approximately 1.6 million and 10.5 million individuals). Each
      sales data of eradication packages and examination kits were used to estimate the
      number of H. pylori-eradicated individuals nationwide. The prevalence of H.
      pylori infection, including the future rate, was predicted using previous studies
      and the estimated population trend by a national institute. Cases completed prior
      to the policy change on insurance coverage were simulated to estimate what would
      have happened had there been no change in the policy. RESULTS: The numbers of
      patients first received eradication therapy were 81 119 and 170 993 from two
      databases. The nationwide estimated number of patients successfully eradicated
      was approximately 650 000 per year between 2001 and 2012, whereas it rapidly rose
      to 1 380-000 per year in 2013. The estimated prevalence of infection in 2050 is
      5%, this rate was estimated to be 28% and 22% if the policy changes had not
      occurred in 2000 and 2013, respectively. CONCLUSIONS: The impact of policy
      changes for H. pylori eradication therapy on the prevalence of infection was
      shown. The results suggest that insurance coverage expansion may also reduce the
      prevalence in other countries with a high prevalence of H. pylori infection if
      the reinfection is low.

PMID- 28760791
TI  - Prevalence and prescription patterns of oral glucocorticoids in adults: a
      retrospective cross-sectional and cohort analysis in France.
AB  - OBJECTIVES: To study trends in use of oral glucocorticoids (GCs) among adults,
      characteristics of oral GC initiators and prescriptions for the prevention of
      potential adverse effects associated with GC therapy. DESIGN: First, a cross
      sectional study repeated yearly was performed from 2007 to 2014 in a nationwide
      representative sample. Second, characteristics of initiators and patterns of GC
      therapy during the year following treatment initiation were described in a cohort
      of patients who began GC between 2007 and 2013. SETTING: Population-based study
      using data from the French reimbursement healthcare system (covering
      approximately 90% of the population) in patients aged >=18 years. RESULTS: Over
      the study period, the prevalence of oral GC use ranged from 14.7% to 17.1% (95%
      CI 17.0%-17.2%) with a significant increase of 14.1% (95% CI +13.5% to +14.8%).
      The 2007-2013 cohort of oral GC initiators comprised 206 759 individuals. Oral GC
      use was mostly short-term (68% of unique reimbursement) and more than half of
      short-term users took concurrent antibiotics or respiratory/otological drugs.
      Chronic users (>=6 reimbursements/year) represented 1.8% (n=3789) of the cohort.
      The proportion of chronic users with comorbidities likely to be worsened by GC
      use (diabetes, psychotic disorders, osteoporosis) was 25%. Among patients at
      increased risk of osteoporosis, 62% received specific prevention/monitoring
      measures and only 27% had a bisphosphonate. Half of chronic oral GC users had a
      concurrent reimbursement of a proton pump inhibitor in the absence of non
      steroidal anti-inflammatory drug use. CONCLUSIONS: Oral GC use was highly
      widespread and increased among adults from 2007 to 2014. The overwhelming short
      term use could mainly concern a growing use of unjustified prescriptions rather
      than situations with a favourable benefit/risk ratio. For chronic users, our
      findings plead for the development of interventions designed to improve
      monitoring with regard to the frequent comorbidities at risk and inappropriate
      prescribing of preventive therapeutic measures.

PMID- 28760792
TI  - Glycated haemoglobin A1c as a risk factor of cardiovascular outcomes and all
      cause mortality in diabetic and non-diabetic populations: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To examine the relationship between glycated haemoglobin A1c (HbA1c)
      levels and the risk of cardiovascular outcomes and all-cause mortality based on
      data from observational studies and to determine the optimal levels of HbA1c for
      preventing cardiovascular events and/or mortality in diabetic and non-diabetic
      populations. REVIEW METHODS: We systematically searched Medline, Embase, the
      Cochrane Central Register of Controlled Trials, the Cochrane Database of
      Systematic Reviews and Web of Science databases, from inception to July 2016, for
      observational studies addressing the association of HbA1c levels with mortality
      and cardiovascular outcomes. Random effects models were used to compute pooled
      estimates of HR and respective 95% CI for all-cause mortality, cardiovascular
      mortality and risk of cardiovascular events, separately for people with and
      without diabetes. RESULTS: Seventy-four published studies were included in the
      systematic review, but only 46 studies could be incorporated in the meta
      analysis. In both diabetic and non-diabetic populations, there was an increase in
      the risk of all-cause mortality when HbA1c levels were over 8.0% and 6.0%,
      respectively. The highest all-cause mortality in people with diabetes was HbA1c
      above 9.0% (HR=1.69; 95% CI 1.09 to 2.66) and in those without diabetes was HbA1c
      above 6.0% (HR=1.74; 95% CI 1.38 to 2.20). However, both diabetic and non
      diabetic populations with lower HbA1c levels (below 6.0% HR=1.57; 95% CI 1.14 to
      2.17 and below 5.0% HR=1.19; 95% CI 1.04 to 1.36, respectively) had higher all
      cause mortality. Similar pooled estimates were found when cardiovascular
      mortality was the outcome variable. CONCLUSION: HbA1c is a reliable risk factor
      of all-cause and cardiovascular mortality in both diabetics and non-diabetics.
      Our findings establish optimal HbA1c levels, for the lowest all-cause and
      cardiovascular mortality, ranging from 6.0% to 8.0% in people with diabetes and
      from 5.0% to 6.0% in those without diabetes.

PMID- 28760793
TI  - PIM-Check: development of an international prescription-screening checklist
      designed by a Delphi method for internal medicine patients.
AB  - OBJECTIVES: Potentially inappropriate medication (PIM) occurs frequently and is a
      well-known risk factor for adverse drug events, but its incidence is
      underestimated in internal medicine. The objective of this study was to develop
      an electronic prescription-screening checklist to assist residents and young
      healthcare professionals in PIM detection. DESIGN: Five-step study involving
      selection of medical domains, literature review and 17 semistructured interviews,
      a two-round Delphi survey, a forward/back-translation process and an electronic
      tool development. SETTING: 22 University and general hospitals from Canada,
      Belgium, France and Switzerland. PARTICIPANTS: 40 physicians and 25 clinical
      pharmacists were involved in the study.Agreement with the checklist statements
      and their usefulness for healthcare professional training were evaluated using
      two 6-point Likert scales (ranging from 0 to 5). PRIMARY AND SECONDARY OUTCOME
      MEASURES: Agreement and usefulness ratings were defined as: >65% of the experts
      giving the statement a rating of 4 or 5, during the first Delphi-round and >75%
      during the second. RESULTS: 166 statements were generated during the first two
      steps. Mean agreement and usefulness ratings were 4.32/5 (95% CI 4.28 to 4.36)
      and 4.11/5 (4.07 to 4.15), respectively, during the first Delphi-round and 4.53/5
      (4.51 to 4.56) and 4.36/5 (4.33 to 4.39) during the second (p<0.001). The final
      checklist includes 160 statements in 17 medical domains and 56 pathologies. An
      algorithm of approximately 31 000 lines was developed including comorbidities and
      medications variables to create the electronic tool. CONCLUSION: PIM-Check is the
      first electronic prescription-screening checklist designed to detect PIM in
      internal medicine. It is intended to help young healthcare professionals in their
      clinical practice to detect PIM, to reduce medication errors and to improve
      patient safety.

PMID- 28760794
TI  - Comparison of a 'freeze-all' strategy including GnRH agonist trigger versus a
      'fresh transfer' strategy including hCG trigger in assisted reproductive
      technology (ART): a study protocol for a randomised controlled trial.
AB  - INTRODUCTION: Pregnancy rates after frozen embryo transfer (FET) have improved in
      recent years and are now approaching or even exceeding those obtained after fresh
      embryo transfer. This is partly due to improved laboratory techniques, but may
      also be caused by a more physiological hormonal and endometrial environment in
      FET cycles. Furthermore, the risk of ovarian hyperstimulation syndrome is
      practically eliminated in segmentation cycles followed by FET and the use of
      natural cycles in FETs may be beneficial for the postimplantational conditions of
      fetal development. However, a freeze-all strategy is not yet implemented as
      standard care due to limitations of large randomised trials showing a benefit of
      such a strategy. Thus, there is a need to test the concept against standard care
      in a randomised controlled design. This study aims to compare ongoing pregnancy
      and live birth rates between a freeze-all strategy with gonadotropin-releasing
      hormone (GnRH) agonist triggering versus human chorionic gonadotropin (hCG)
      trigger and fresh embryo transfer in a multicentre randomised controlled trial.
      METHODS AND ANALYSIS: Multicentre randomised, controlled, double-blinded trial of
      women undergoing assisted reproductive technology treatment including 424 normo
      ovulatory women aged 18-39 years from Denmark and Sweden. Participants will be
      randomised (1:1) to either (1) GnRH agonist trigger and single vitrified-warmed
      blastocyst transfer in a subsequent hCG triggered natural menstrual cycle or (2)
      hCG trigger and single blastocyst transfer in the fresh (stimulated) cycle. The
      primary endpoint is to compare ongoing pregnancy rates per randomised patient in
      the two treatment groups after the first single blastocyst transfer. ETHICS AND
      DISSEMINATION: The study will be performed in accordance with the ethical
      principles in the Helsinki Declaration. The study is approved by the Scientific
      Ethical Committees in Denmark and Sweden. The results of the study will be
      publically disseminated. TRIAL REGISTRATION NUMBER: NCT02746562; Pre-results.

PMID- 28760795
TI  - Workforce characteristics and interventions associated with high-quality care and
      support to older people with cancer: a systematic review.
AB  - OBJECTIVES: To provide an overview of the evidence base on the effectiveness of
      workforce interventions for improving the outcomes for older people with cancer,
      as well as analysing key features of the workforce associated with those
      improvements. DESIGN: Systematic review. METHODS: Relevant databases were
      searched for primary research, published in English, reporting on older people
      and cancer and the outcomes of interventions to improve workforce knowledge,
      attitudes or skills; involving a change in workforce composition and/or skill
      mix; and/or requiring significant workforce reconfiguration or new roles. Studies
      were also sought on associations between the composition and characteristics of
      the cancer care workforce and older people's outcomes. A narrative synthesis was
      conducted and supported by tabulation of key study data. RESULTS: Studies (n=24)
      included 4555 patients aged 60+ from targeted cancer screening to end of life
      care. Interventions were diverse and two-thirds of the studies were assessed as
      low quality. Only two studies directly targeted workforce knowledge and skills
      and only two studies addressed the nature of workforce features related to
      improved outcomes. Interventions focused on discrete groups of older people with
      specific needs offering guidance or psychological support were more effective
      than those broadly targeting survival outcomes. Advanced Practice Nursing roles,
      voluntary support roles and the involvement of geriatric teams provided some
      evidence of effectiveness. CONCLUSIONS: An array of workforce interventions focus
      on improving outcomes for older people with cancer but these are diverse and
      thinly spread across the cancer journey. Higher quality and larger scale research
      that focuses on workforce features is now needed to guide developments in this
      field, and review findings indicate that interventions targeted at specific
      subgroups of older people with complex needs, and that involve input from
      advanced practice nurses, geriatric teams and trained volunteers appear most
      promising.

PMID- 28760796
TI  - Past speculations of future health technologies: a description of technologies
      predicted in 15 forecasting studies published between 1986 and 2010.
AB  - OBJECTIVE: To describe and classify health technologies predicted in forecasting
      studies. DESIGN AND METHODS: A portrait describing health technologies predicted
      in 15 forecasting studies published between 1986 and 2010 that were identified in
      a previous systematic review. Health technologies are classified according to
      their type, purpose and clinical use; relating these to the original purpose and
      timing of the forecasting studies. DATA SOURCES: All health-related technologies
      predicted in 15 forecasting studies identified in a previously published
      systematic review. MAIN OUTCOME MEASURE: Outcomes related to (1) each forecasting
      study including country, year, intention and forecasting methods used and (2) the
      predicted technologies including technology type, purpose, targeted clinical area
      and forecast timeframe. RESULTS: Of the 896 identified health-related
      technologies, 685 (76.5%) were health technologies with an explicit or implied
      health application and included in our study. Of these, 19.1% were diagnostic or
      imaging tests, 14.3% devices or biomaterials, 12.6% information technology
      systems, eHealth or mHealth and 12% drugs. The majority of the technologies were
      intended to treat or manage disease (38.1%) or diagnose or monitor disease
      (26.1%). The most frequent targeted clinical areas were infectious diseases
      followed by cancer, circulatory and nervous system disorders. The most frequent
      technology types were for: infectious diseases-prophylactic vaccines (45.8%),
      cancer-drugs (40%), circulatory disease-devices and biomaterials (26.3%), and
      diseases of the nervous system-equally devices and biomaterials (25%) and
      regenerative medicine (25%). The mean timeframe for forecasting was 11.6 years
      (range 0-33 years, median=10, SD=6.6). The forecasting timeframe significantly
      differed by technology type (p=0.002), the intent of the forecasting group
      (p<0.001) and the methods used (p<001). CONCLUSION: While description and
      classification of predicted health-related technologies is crucial in preparing
      healthcare systems for adopting new innovations, further work is needed to test
      the accuracy of predictions made.

PMID- 28760797
TI  - Sugar-sweetened beverage consumption, correlates and interventions among
      Australian Aboriginal and Torres Strait Islander communities: a scoping review
      protocol.
AB  - INTRODUCTION: Aboriginal and Torres Strait Islander communities of Australia
      experience poorer health outcomes in the areas of overweight and obesity,
      diabetes and cardiovascular disease. Contributing to this burden of disease in
      the Australian community generally and in Aboriginal and Torres Strait Islander
      communities, is the consumption of sugar-sweetened beverages (SSBs). We have
      described a protocol for a review to systematically scope articles that document
      use of SSBs and interventions to reduce their consumption with Aboriginal and
      Torres Strait Islander people. These results will inform future work that
      investigates interventions aimed at reducing harm associated with SSB
      consumption. METHODS AND ANALYSIS: This scoping review draws on a methodology
      that uses a six-step approach to search databases including PubMed, SCOPUS,
      CINAHL, Informit (including Informit: Indigenous Peoples), Joanna Briggs
      Institute EBP Database and Mura, between January 1980 and February 2017. Two
      reviewers will be engaged to search for and screen studies independently, using
      formulated selection criteria, for inclusion in our review. We will include
      primary research studies, systematic reviews including meta-analysis or meta
      synthesis, reports and unpublished grey literature. Results will be entered into
      a table identifying study details and characteristics, summarised using a
      Preferred Reporting Items for Systematic Reviews and Meta-Analysis chart and then
      critically analysed. ETHICS AND DISSEMINATION: This review will not require
      ethics committee review. Results will be disseminated at appropriate scientific
      meetings, as well as through the Aboriginal and Torres Strait Islander community.

PMID- 28760798
TI  - Protocol for a randomised crossover trial to evaluate patient and nurse
      satisfaction with electronic and elastomeric portable infusion pumps for the
      continuous administration of antibiotic therapy in the home: the Comparing Home
      Infusion Devices (CHID) study.
AB  - INTRODUCTION: Previous studies comparing satisfaction with electronic and
      elastomeric infusion pumps are limited, and improvements in size and usability of
      electronic pumps have since occurred. The Comparing Home Infusion Devices (CHID)
      study plans to assess patient and nurse satisfaction with an elastomeric and
      electronic pump for delivering intravenous antibiotic treatment in the home.
      Secondary objectives are to determine pump-related complications and actual
      antibiotic dose administered, evaluate temperature variation and compare pump
      operating costs. METHODS AND ANALYSIS: The CHID study will be a randomised,
      crossover trial. A trained research nurse will recruit patients with infectious
      disease aged >=18 years and prescribed >=8 days of continuous intravenous
      antibiotic therapy from the Royal Adelaide Hospital (RAH) (Adelaide, Australia).
      Patients will be randomised to receive treatment at home via an elastomeric
      (Baxter Infusor) or an electronic (ambIT Continuous) infusion pump for 4-7 days,
      followed by the other for a further 4-7 days. Patient satisfaction will be
      assessed by a 10-item survey to be completed at the end of each arm. Nurse
      satisfaction will be assessed by a single 24-item survey. Patient logbooks and
      case notes from clinic visits will be screened to identify complications.
      Pumps/infusion bags will be weighed to estimate the volume of solution delivered.
      Temperature sensors will record skin and ambient temperatures during storage and
      use of the pumps throughout the infusion period. Costs relating to pumps,
      consumables, antibiotics and servicing will be determined. Descriptive statistics
      will summarise study data. ETHICS AND DISSEMINATION: This study has been approved
      by the RAH Human Research Ethics Committee (HREC/16/RAH/133 R20160420, version
      6.0, 5 September 2016). Study results will be disseminated through peer-reviewed
      publications and conference presentations. The CHID study will provide key
      insights into patient and provider satisfaction with elastomeric and electronic
      infusion pumps and inform future device selection. TRIAL REGISTRATION NUMBER:
      ACTRN12617000251325; Pre-results.

PMID- 28760801
TI  - Polyethylene glycol intestinal lavage in addition to usual antibiotic treatment
      for severe Clostridium difficile colitis: a randomised controlled pilot study.
AB  - INTRODUCTION: Clostridium difficile infections (CDI) are common, costly and
      potentially life threatening. Most CDI will respond to antibiotic therapy, but 3%
      10% of all patients with CDI will progress to a severe, life-threatening course.
      Complete removal of the large bowel is indicated for severe CDI. However, the 30
      day mortality following surgical intervention for severe CDI ranges from 20% to
      70%. A less invasive approach using surgical faecal diversion and direct colonic
      lavage with polyethylene glycol (PEG) and vancomycin has demonstrated a relative
      mortality reduction of approximately 50%. As an alternative to these operative
      approaches, we propose to treat patients with bedside intestinal lavage with PEG
      and vancomycin instillation via nasojejunal tube, in addition to usual antibiotic
      management. Preliminary data collected by our research group are encouraging.
      METHODS AND ANALYSIS: We will conduct a 1-year, single-centre, pilot randomised
      controlled trial to study this new treatment strategy for patients with severe
      CDI and additional risk factors for fulminant or complicated infection. After
      informed consent, patients with severe-complicated CDI without immediate
      indication for surgery will be randomised to either usual antibiotic treatment or
      usual antibiotic treatment with the addition of 8 L of PEG lavage via nasojejunal
      tube. This pilot trial will evaluate our eligibility and enrolment rate, protocol
      compliance and adverse event rates and provide further data to inform a more
      robust sample size calculation and protocol modifications for a definitive
      multicentre trial design. Based on historical data, we anticipate enrolling
      approximately 24 patients during the 1-year pilot study period.As a pilot study,
      data will be reported in aggregate. Between-group differences will be assessed in
      a blinded fashion for evidence of harm, and to further refine our sample size
      calculation. ETHICS AND DISSEMINATION: This study protocol has been reviewed and
      approved by our local institutional review board. Results of the pilot trial and
      subsequent main trial will be submitted for publication in a peer-reviewed
      journal. TRIAL REGISTRATION NUMBER: NCT02466698; Pre-results.

PMID- 28760799
TI  - Rationale and study design for an individualised perioperative open-lung
      ventilatory strategy with a high versus conventional inspiratory oxygen fraction
      (iPROVE-O2) and its effects on surgical site infection: study protocol for a
      randomised controlled trial.
AB  - INTRODUCTION: Surgical site infection (SSI) is a serious postoperative
      complication that increases morbidity and healthcare costs. SSIs tend to increase
      as the partial pressure of tissue oxygen decreases: previous trials have focused
      on trying to reduce them by comparing high versus conventional inspiratory oxygen
      fractions (FIO2) in the perioperative period but did not use a protocolised
      ventilatory strategy. The open-lung ventilatory approach restores functional lung
      volume and improves gas exchange, and therefore it may increase the partial
      pressure of tissue oxygen for a given FIO2. The trial presented here aims to
      compare the efficacy of high versus conventional FIO2 in reducing the overall
      incidence of SSIs in patients by implementing a protocolised and individualised
      global approach to perioperative open-lung ventilation. METHODS AND ANALYSIS:
      This is a comparative, prospective, multicentre, randomised and controlled two
      arm trial that will include 756 patients scheduled for abdominal surgery. The
      patients will be randomised into two groups: (1) a high FIO2 group (80% oxygen;
      FIO2 of 0.80) and (2) a conventional FIO2 group (30% oxygen; FIO2 of 0.30). Each
      group will be assessed intra- and postoperatively. The primary outcome is the
      appearance of postoperative SSI complications. Secondary outcomes are the
      appearance of systemic and pulmonary complications. ETHICS AND DISSEMINATION: The
      iPROVE-O2 trial has been approved by the Ethics Review Board at the reference
      centre (the Hospital Clinico Universitario in Valencia). Informed consent will be
      obtained from all patients before their participation. If the approach using high
      FIO2 during individualised open-lung ventilation decreases SSIs, use of this
      method will become standard practice for patients scheduled for future abdominal
      surgery. Publication of the results is anticipated in early 2019. TRIAL
      REGISTRATION NUMBER: NCT02776046; Pre-results.

PMID- 28760803
TI  - Cheap, undervalued, expendable: junior doctors in 2017?

PMID- 28760802
TI  - This Much Water: a qualitative study using behavioural theory to develop a
      community service video to prevent child drowning in Western Australia.
AB  - OBJECTIVES: Drowning in children under the age of 5 is a frequently occurring,
      yet preventable event. This research used behavioural theory to test the
      suitability and appropriateness of a drowning prevention message in a community
      service video. DESIGN: This qualitative study used content analysis of focus
      groups. Constructs from the Health Belief Model guided the data analysis.
      SETTING: Community organisations and playgrounds in Perth, Western Australia.
      PARTICIPANTS: Participants were parents or carers of at least one child under 5
      years residing in Western Australia. Seven focus groups (n=57) were conducted
      with eight participants in each group. Most participants were parents (96%),
      female (95%), aged between 25 and 34 years (63%) and were born in Australia
      (68%). RESULTS: Participants indicated the community service video was credible
      in communicating the message that young children were susceptible to drowning in
      shallow water and that various water hazards existed in and around the home.
      However, a range of external factors, such as the child's age, type of water
      hazard, presence of siblings and other environmental factors, influenced risk
      perceptions. Child drowning was seen as a serious issue. Controlling access to
      water and the role of supervision were understood to be important factors in
      preventing drowning. CONCLUSIONS: The lack of published drowning prevention
      interventions shaped by behavioural theory limits the understanding of best
      practice. Using constructs from the Health Belief Model, this research confirmed
      the perceived seriousness, devastating and unforgettable consequence of drowning;
      however, findings were mixed regarding cues to action. Future development of
      drowning prevention media messages should test strategies to increase
      susceptibility and self-efficacy among the target group and explore the impact of
      different message senders. The findings provide a valuable understanding of
      possible messages and their execution for use in media campaigns, as one
      component of an effective public health intervention to prevent child drowning
      underpinned by behavioural theory.

PMID- 28760800
TI  - Protocol for a prospective longitudinal study of risk factors for hypertension
      incidence in a Mexico City population: the Tlalpan 2020 cohort.
AB  - INTRODUCTION: Systemic hypertension (HTN) is a common risk factor for
      cardiovascular disease. In Mexico, HTN prevalence has increased over time and is
      currently 31%. Nonetheless, information about the country's HTN incidence and its
      associated risk factors is scarce. Understanding this condition is a priority for
      identifying the scope of primary prevention. The main objective of this study is
      to evaluate the effect of traditional and non-traditional risk factors on the
      incidence of HTN in a cohort of healthy Mexico City residents under biannual
      follow-up for 10 years. METHODS AND ANALYSIS: A prospective longitudinal study is
      proposed in which clinically healthy residents of Mexico City between 20 and 50
      years old will be recruited; the participants will be evaluated every 2 years
      over a period of 10 years or until they develop HTN. Evaluations regarding
      sociodemographic, clinical, anthropometric, biochemical, diet, physical activity,
      stress, sleep quality, alcohol and tobacco consumption factors will be performed.
      The participants will be recruited from the 16 municipalities of Mexico City
      through promotional strategies aimed at the community and will be clinically
      evaluated at a tertiary care institution, Instituto Nacional de Cardiologia
      Ignacio Chavez (National Institute of Cardiology Ignacio Chavez), located in
      Mexico City, Mexico. Sample size estimated for this study is 3436, and the Cox
      proportional hazards model will be used to estimate HRs for the association
      between explanatory variables and HTN using both raw and adjusted data. ETHICS
      AND DISSEMINATION: This study was approved by the Institutional Bioethics
      Committee of the Instituto Nacional de Cardiologia Ignacio Chavez (National
      Institute of Cardiology Ignacio Chavez) under number 13-802. Findings from this
      study will be disseminated through scientific papers and research conferences.

PMID- 28760804
TI  - Thousands more mental health posts will be created in England.

PMID- 28760806
TI  - p27 in FLT3-driven acute myeloid leukemia: many roads lead to ruin.

PMID- 28760807
TI  - Long non-coding RNAs: another brick in the wall of normal karyotype acute myeloid
      leukemia?

PMID- 28760808
TI  - Charlie Gard dies in hospice after High Court rules against prolonging life
      support.

PMID- 28760805
TI  - H1N1 vaccination in Sjogren's syndrome triggers polyclonal B cell activation and
      promotes autoantibody production.
AB  - OBJECTIVES: Vaccination of patients with rheumatic disease has been reported to
      result in lower antibody titres than in healthy individuals. However, studies
      primarily include patients on immunosuppressive therapy. Here, we investigated
      the immune response of treatment-naive patients diagnosed with primary Sjogren's
      syndrome (pSS) to an H1N1 influenza vaccine. METHODS: Patients with Sjogren's
      syndrome without immunomodulatory treatment and age-matched and gender-matched
      healthy controls were immunised with an H1N1 influenza vaccine and monitored for
      serological and cellular immune responses. Clinical symptoms were monitored with
      a standardised form. IgG class switch and plasma cell differentiation were
      induced in vitro in purified naive B cells of untreated and hydroxychloroquine
      treated patients and healthy controls. Gene expression was assessed by NanoString
      technology. RESULTS: Surprisingly, treatment-naive patients with Sjogren's
      syndrome developed higher H1N1 IgG titres of greater avidity than healthy
      controls on vaccination. Notably, off-target B cells were also triggered
      resulting in increased anti-EBV and autoantibody titres. Endosomal toll-like
      receptor activation of naive B cells in vitro revealed a greater propensity of
      patient-derived cells to differentiate into plasmablasts and higher production of
      class switched IgG. The amplified plasma cell differentiation and class switch
      could be induced in cells from healthy donors by preincubation with type 1
      interferon, but was abolished in hydroxychloroquine-treated patients and after in
      vitro exposure of naive B cells to chloroquine. CONCLUSIONS: This comprehensive
      analysis of the immune response in autoimmune patients to exogenous stimulation
      identifies a mechanistic basis for the B cell hyperactivity in Sjogren's
      syndrome, and suggests that caution is warranted when considering vaccination in
      non-treated autoimmune patients.

PMID- 28760810
TI  - Morphogen and community effects determine cell fates in response to BMP4
      signaling in human embryonic stem cells.
AB  - Paracrine signals maintain developmental states and create cell fate patterns in
      vivo and influence differentiation outcomes in human embryonic stem cells (hESCs)
      in vitro Systematic investigation of morphogen signaling is hampered by the
      difficulty of disentangling endogenous signaling from experimentally applied
      ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells
      ('uColonies') to quantitatively investigate paracrine signaling and the response
      to external stimuli. We examine BMP4-mediated differentiation in uColonies and
      standard culture conditions and find that in uColonies, above a threshold
      concentration, BMP4 gives rise to only a single cell fate, contrary to its role
      as a morphogen in other developmental systems. Under standard culture conditions
      BMP4 acts as a morphogen but this requires secondary signals and particular cell
      densities. We find that a 'community effect' enforces a common fate within
      uColonies, both in the state of pluripotency and when cells are differentiated,
      and that this effect allows a more precise response to external signals. Using
      live cell imaging to correlate signaling histories with cell fates, we
      demonstrate that interactions between neighbors result in sustained, homogenous
      signaling necessary for differentiation.

PMID- 28760811
TI  - Patterning of the Drosophila L2 vein is driven by regulatory interactions between
      region-specific transcription factors expressed in response to Dpp signalling.
AB  - Pattern formation relies on the generation of transcriptional landscapes
      regulated by signalling pathways. A paradigm of epithelial patterning is the
      distribution of vein territories in the Drosophila wing disc. In this tissue,
      Decapentaplegic signalling regulates its target genes at different distances from
      the source of the ligand. The transformation of signalling into coherent
      territories of gene expression requires regulatory cross-interactions between
      these target genes. Here, we analyse the mechanisms generating the domain of
      knirps expression in the presumptive L2 vein of the wing imaginal disc. We find
      that knirps is regulated by four Decapentaplegic target genes encoding the
      transcription factors aristaless, spalt major, spalt-related and optix The
      expression of optix is activated by Dpp and repressed by the Spalt proteins,
      becoming restricted to the most anterior region of the wing blade. In turn, the
      expression of knirps is activated by Aristaless and repressed by Optix and the
      Spalt proteins. In this manner, the expression of knirps becomes restricted to
      those cells where Spalt levels are sufficient to repress optix, but not
      sufficient to repress knirps.

PMID- 28760809
TI  - Genome-wide identification of Grainy head targets in Drosophila reveals
      regulatory interactions with the POU domain transcription factor Vvl.
AB  - Grainy head (Grh) is a conserved transcription factor (TF) controlling epithelial
      differentiation and regeneration. To elucidate Grh functions we identified
      embryonic Grh targets by ChIP-seq and gene expression analysis. We show that Grh
      controls hundreds of target genes. Repression or activation correlates with the
      distance of Grh-binding sites to the transcription start sites of its targets.
      Analysis of 54 Grh-responsive enhancers during development and upon wounding
      suggests cooperation with distinct TFs in different contexts. In the airways, Grh
      repressed genes encode key TFs involved in branching and cell differentiation.
      Reduction of the POU domain TF Ventral veins lacking (Vvl) largely ameliorates
      the airway morphogenesis defects of grh mutants. Vvl and Grh proteins
      additionally interact with each other and regulate a set of common enhancers
      during epithelial morphogenesis. We conclude that Grh and Vvl participate in a
      regulatory network controlling epithelial maturation.

PMID- 28760812
TI  - Functional regulatory evolution outside of the minimal even-skipped stripe 2
      enhancer.
AB  - Transcriptional enhancers are regions of DNA that drive precise patterns of gene
      expression. Although many studies have elucidated how individual enhancers can
      evolve, most of this work has focused on what are called 'minimal' enhancers, the
      smallest DNA regions that drive expression that approximates an aspect of native
      gene expression. Here, we explore how the Drosophila erecta even-skipped (eve)
      locus has evolved by testing its activity in the divergent D. melanogaster
      genome. We found, as has been reported previously, that the D. erecta eve stripe
      2 enhancer (eveS2) fails to drive appreciable expression in D. melanogaster
      However, we found that a large transgene carrying the entire D. erecta eve locus
      drives normal eve expression, including in stripe 2. We performed a functional
      dissection of the region upstream of the D. erecta eveS2 region and found
      multiple Zelda motifs that are required for normal expression. Our results
      illustrate how sequences outside of minimal enhancer regions can evolve
      functionally through mechanisms other than changes in transcription factor
      binding sites that drive patterning.

PMID- 28760813
TI  - The extracellular metalloprotease AdamTS-A anchors neural lineages in place
      within and preserves the architecture of the central nervous system.
AB  - The extracellular matrix (ECM) regulates cell migration and sculpts organ shape.
      AdamTS proteins are extracellular metalloproteases known to modify ECM proteins
      and promote cell migration, but demonstrated roles for AdamTS proteins in
      regulating CNS structure and ensuring cell lineages remain fixed in place have
      not been uncovered. Using forward genetic approaches in Drosophila, we find that
      reduction of AdamTS-A function induces both the mass exodus of neural lineages
      out of the CNS and drastic perturbations to CNS structure. Expressed and active
      in surface glia, AdamTS-A acts in parallel to perlecan and in opposition to
      viking/collagen IV and betaPS-integrin to keep CNS lineages rooted in place and
      to preserve the structural integrity of the CNS. viking/collagen IV and betaPS
      integrin are known to promote tissue stiffness and oppose the function of
      perlecan, which reduces tissue stiffness. Our work supports a model in which
      AdamTS-A anchors cells in place and preserves CNS architecture by reducing tissue
      stiffness.

PMID- 28760816
TI  - Mandela doctor's book is withdrawn for possible breach of confidentiality.

PMID- 28760815
TI  - Endothelial cells respond to the direction of mechanical stimuli through SMAD
      signaling to regulate coronary artery size.
AB  - How mechanotransduction intersects with chemical and transcriptional factors to
      shape organogenesis is an important question in developmental biology. This is
      particularly relevant to the cardiovascular system, which uses mechanical signals
      from flowing blood to stimulate cytoskeletal and transcriptional responses that
      form a highly efficient vascular network. Using this system, artery size and
      structure are tightly regulated, but the underlying mechanisms are poorly
      understood. Here, we demonstrate that deletion of Smad4 increased the diameter of
      coronary arteries during mouse embryonic development, a phenotype that followed
      the initiation of blood flow. At the same time, the BMP signal transducers
      SMAD1/5/8 were activated in developing coronary arteries. In a culture model of
      blood flow-induced shear stress, human coronary artery endothelial cells failed
      to align when either BMPs were inhibited or SMAD4 was depleted. In contrast to
      control cells, SMAD4-deficient cells did not migrate against the direction of
      shear stress and increased proliferation rates specifically under flow. Similar
      alterations were seen in coronary arteries in vivo Thus, endothelial cells
      perceive the direction of blood flow and respond through SMAD signaling to
      regulate artery size.

PMID- 28760817
TI  - Non-pharmacological interventions for management of fatigue among children with
      cancer: systematic review of existing practices and their effectiveness.
AB  - OBJECTIVES: Fatigue is common among children living with cancer, particularly in
      advance stages. Little is known about the effectiveness of non-pharmacological
      approaches to manage this complex and distressing symptom among children. Thus,
      the present paper aim to critically examine the effectiveness and setting for non
      pharmacological interventions to manage fatigue among children with cancer.
      METHODS: Six electronic databases were screened first in February 2013 and at
      second instance in March 2015. They include PsycINFO, Medline, EMBASE, CINAHL,
      Scopus and Cochrane library. All databases were systematically searched for
      literature on fatigue and cancer, limited to children (as age group) and English
      language. RESULTS: 1498 articles were identified, of which six were reviewed.
      Three types of interventions for managing fatigue were identified including (1)
      complementary and alternative medicine (healing touch/massage therapy), (2)
      exercise-based interventions and (3) nursing-based interventions. Most
      interventions were delivered during active treatment and in hospital settings
      where parents were involved to optimise participation. Despite fatigue scores
      being lower among intervention groups, no study findings were observed as being
      statistically significant. CONCLUSION: Fatigue is common among children treated
      for and living with cancer. The most appropriate setting to deliver non
      pharmacological interventions to manage fatigue appears to be in hospital.
      However, in absence of any strong evidence, professionals need to be cautious
      about existing non-pharmacological interventions. Future research must adopt more
      rigorous research designs that are adequately powered using validated measures to
      identify potential benefits. In addition, researchers may wish to test
      psychosocial interventions shown to be of benefit in adults.

PMID- 28760814
TI  - A Sall1-NuRD interaction regulates multipotent nephron progenitors and is
      required for loop of Henle formation.
AB  - The formation of the proper number of nephrons requires a tightly regulated
      balance between renal progenitor cell self-renewal and differentiation. The
      molecular pathways that regulate the transition from renal progenitor to renal
      vesicle are not well understood. Here, we show that Sall1interacts with the
      nucleosome remodeling and deacetylase complex (NuRD) to inhibit premature
      differentiation of nephron progenitor cells. Disruption of Sall1-NuRD in vivo in
      knock-in mice (DeltaSRM) resulted in accelerated differentiation of nephron
      progenitors and bilateral renal hypoplasia. Transcriptional profiling of mutant
      kidneys revealed a striking pattern in which genes of the glomerular and proximal
      tubule lineages were either unchanged or upregulated, and those in the loop of
      Henle and distal tubule lineages were downregulated. These global changes in gene
      expression were accompanied by a significant decrease in THP-, NKCC2- and AQP1
      positive loop of Henle nephron segments in mutant DeltaSRM kidneys. These
      findings highlight an important function of Sall1-NuRD interaction in the
      regulation of Six2-positive multipotent renal progenitor cells and formation of
      the loop of Henle.

PMID- 28760818
TI  - Research protocol on early palliative care in patients with acute leukaemia after
      one relapse.
AB  - OBJECTIVES: According to the American Society of Clinical Oncology palliative
      care referrals are made within the last 3 weeks of patients' lives and most
      frequently when oncological treatments have ceased especially for patients with
      haematological malignancies. Recent publications indicate that patients with
      acute leukaemia are prone to symptoms, an indication for which a close
      collaboration between the patient's haematologist and a palliative care team
      might result in improved symptom management. The object of this pilot study is to
      evaluate the feasibility of a clinical research trial to assess the effect of
      early palliative care in patients with acute leukaemia after one relapse.
      METHODS: This project is a multicentre, non-blinded, randomised, controlled
      trial. Patients in group 1 will receive standard haematological care associated
      with palliative care (intervention group). Patients in group 2 will receive
      standard haematological care with palliative care only if requested by the
      haematologist (control group). In order to measure an accurate sample size,
      patients who participate will complete a standardised questionnaire to assess
      their quality of life, as well as their psychological and physical symptoms,
      before being randomised to one of two groups in a 1:1 ratio without stratified
      randomisation. RESULTS: The aim of this study is to analyse causes of dropout,
      non-adherence and missing data in order to refine the protocol for the subsequent
      clinical research trial. CONCLUSION: The ultimate objective of this project is to
      develop collaboration between haematologists and palliative care teams in order
      to improve patients' quality of life.

PMID- 28760819
TI  - A qualitative inquiry into the barriers and facilitators to achieving home death.
AB  - OBJECTIVES: To explore the barriers and facilitators to patients achieving death
      at home. METHODS: In-depth, semistructured interviews with end-of-life care
      experts were conducted to develop an insight into the barriers and facilitators
      to achieving death at home. Thirty-three interviews were conducted compromising
      of a mixture of face-to-face and tele interviews. Experts included healthcare
      professionals working in the community, hospital and policy/academic settings.
      Thematic analysis was undertaken on interview transcripts. RESULTS: Three
      overarching themes, further divided into a total of 12 subthemes were identified.
      The three themes were 'managing people', 'education' and 'planning'. The
      'managing people' theme included subthemes of patient preferences and family
      influences; the 'education' theme encompassed knowledge and training, perceptions
      of death and communication and the 'planning' theme contained seven subthemes
      including 'coordination', 'resources' and 'cost'. CONCLUSIONS: Multiple barriers
      and facilitators to achieving death at home were identified in this study. Of
      particular significance was the identification of the fear and stigma associated
      with death among doctors, patients and their families serving as a barrier to
      home death, not previously identified in the literature. Additionally, the
      importance of social networks and resource provision were highlighted as key in
      influencing patient death at home.

PMID- 28760820
TI  - Some mental healthcare is "rooted in the past".

PMID- 28760822
TI  - Reactivation of Galphai-coupled formyl peptide receptors is inhibited by Galphaq
      selective inhibitors when induced by signals generated by the platelet-activating
      factor receptor.
AB  - Formyl peptide receptor (FPR)-desensitized neutrophils display increased
      production/release of superoxide (O2-) when activated by platelet-activating
      factor (PAF), a priming of the response achieved through a unique receptor
      crosstalk mechanism. The aim of this study was to determine the effect of an
      inhibitor selective for small, heterotrimeric G proteins belonging to the Galphaq
      subclass on that receptor crosstalk. We show that signals generated by FPRs and
      the PAF receptor (PAFR) induce activation of the neutrophil O2-, producing NADPH
      oxidase, and that response was sensitive to Galphaq inhibition in cells activated
      by PAF, but no inhibition was obtained in cells activated by FPR agonists.
      Signaling in naive neutrophils is terminated fairly rapidly, and the receptors
      become homologously desensitized. The downstream sensitivity to Galphaq
      inhibition in desensitized cells displaying increased production/release of O2-
      through the PAFR receptor crosstalk mechanism also comprised the reactivation of
      the FPRs, and the activation signals were redirected from the PAFR to the
      desensitized/reactivated FPRs. The Galphaq-dependent activation signals generated
      by the PAFRs activate the Galphai-coupled FPRs, a receptor crosstalk that
      represents a novel pathway by which G protein-coupled receptors can be regulated
      and signaling can be turned on and off.

PMID- 28760824
TI  - The glucose sensor Snf1 and the transcription factors Msn2 and Msn4 regulate
      transcription of the vacuolar iron importer gene CCC1 and iron resistance in
      yeast.
AB  - The budding yeast Saccharomyces cerevisiae stores iron in the vacuole, which is a
      major resistance mechanism against iron toxicity. One key protein involved in
      vacuolar iron storage is the iron importer Ccc1, which facilitates iron entry
      into the vacuole. Transcription of the CCC1 gene is largely regulated by the
      binding of iron-sulfur clusters to the activator domain of the transcriptional
      activator Yap5. Additional evidence, however, suggests that Yap5-independent
      transcriptional activation of CCC1 also contributes to iron resistance. Here, we
      demonstrate that components of the signaling pathway involving the low-glucose
      sensor Snf1 regulate CCC1 transcription and iron resistance. We found that SNF1
      deletion acts synergistically with YAP5 deletion to regulate CCC1 transcription
      and iron resistance. A kinase-dead mutation of Snf1 lowered iron resistance as
      did deletion of SNF4, which encodes a partner protein of Snf1. Deletion of all
      three alternative partners of Snf1 encoded by SIT1, SIT2, and GAL83 decreased
      both CCC1 transcription and iron resistance. The Snf1 complex is known to
      activate the general stress transcription factors Msn2 and Msn4. We show that
      Msn2 and Msn4 contribute to Snf1-mediated CCC1 transcription. Of note, SNF1
      deletion in combination with MSN2 and MSN4 deletion resulted in additive effects
      on CCC1 transcription, suggesting that other activators contribute to the
      regulation of CCC1 transcription. In conclusion, we show that yeast have
      developed multiple transcriptional mechanisms to regulate Ccc1 expression and to
      protect against high cytosolic iron toxicity.

PMID- 28760823
TI  - Ascorbate peroxidase proximity labeling coupled with biochemical fractionation
      identifies promoters of endoplasmic reticulum-mitochondrial contacts.
AB  - To maintain cellular homeostasis, subcellular organelles communicate with each
      other and form physical and functional networks through membrane contact sites
      coupled by protein tethers. In particular, endoplasmic reticulum (ER)
      mitochondrial contacts (EMC) regulate diverse cellular activities such as
      metabolite exchange (Ca2+ and lipids), intracellular signaling, apoptosis, and
      autophagy. The significance of EMCs has been highlighted by reports indicating
      that EMC dysregulation is linked to neurodegenerative diseases. Therefore,
      obtaining a better understanding of the physical and functional components of
      EMCs should provide new insights into the pathogenesis of several
      neurodegenerative diseases. Here, we applied engineered ascorbate peroxidase
      (APEX) to map the proteome at EMCs in live HEK293 cells. APEX was targeted to the
      outer mitochondrial membrane, and proximity-labeled proteins were analyzed by
      stable isotope labeling with amino acids in culture (SILAC)-LC/MS-MS. We further
      refined the specificity of the proteins identified by combining biochemical
      subcellular fractionation to the protein isolation method. We identified 405
      proteins with a 2.0-fold cutoff ratio (log base 2) in SILAC quantification from
      replicate experiments. We performed validation screening with a Split-Rluc8
      complementation assay that identified reticulon 1A (RTN1A), an ER-shaping protein
      localized to EMCs as an EMC promoter. Proximity mapping augmented with
      biochemical fractionation and additional validation methods reported here could
      be useful to discover other components of EMCs, identify mitochondrial contacts
      with other organelles, and further unravel their communication.

PMID- 28760825
TI  - Modulation of the extent of structural heterogeneity in alpha-synuclein fibrils
      by the small molecule thioflavin T.
AB  - The transition of intrinsically disordered, monomeric alpha-synuclein into beta
      sheet-rich oligomers and fibrils is associated with multiple neurodegenerative
      diseases. Fibrillar aggregates possessing distinct structures that differ in
      toxicity have been observed in different pathological phenotypes. Understanding
      the mechanism of the formation of various fibril polymorphs with differing
      cytotoxic effects is essential for determining how the aggregation reaction could
      be modulated to favor nontoxic fibrils over toxic fibrils. In this study, two
      morphologically different alpha-synuclein fibrils, one helical and the other
      ribbon-like, are shown to form together. Surprisingly, a widely used small
      molecule for probing aggregation reactions, thioflavin T (ThT), was found to tune
      the structural heterogeneity found in the fibrils. The ribbon-like fibrils formed
      in the presence of ThT were found to have a longer structural core than the
      helical fibrils formed in the absence of ThT. The ribbon-like fibrils are also
      more toxic to cells. By facilitating the formation of ribbon-like fibrils over
      helical fibrils, ThT reduced the extent of fibril polymorphism. This study
      highlights the role of a small molecule such as ThT in selectively favoring the
      formation of a specific type of fibril by binding to aggregates formed early on
      one of multiple pathways, thereby altering the structural core and external
      morphology of the fibrils formed.

PMID- 28760826
TI  - Commensal microbiota-induced microRNA modulates intestinal epithelial
      permeability through the small GTPase ARF4.
AB  - The intestinal tract contains many commensal bacteria that modulate various
      physiological host functions. Dysbiosis of commensal bacteria triggers
      dysfunction of the intestinal epithelial barrier, leading to the induction or
      aggravation of intestinal inflammation. To elucidate whether microRNA plays a
      role in commensal microbiome-dependent intestinal epithelial barrier regulation,
      we compared transcripts in intestinal epithelial cells (IECs) from conventional
      and germ-free mice and found that commensal bacteria induced the expression of
      miR-21-5p in IECs. miR-21-5p increased intestinal epithelial permeability and up
      regulated ADP ribosylation factor 4 (ARF4), a small GTPase, in the IEC line Caco
      2. We also found that ARF4 expression was up-regulated upon suppression of
      phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PDCD4), which
      are known miR-21-5p targets, by RNAi. Furthermore, ARF4 expression in epithelial
      cells of the large intestine was higher in conventional mice than in germ-free
      mice. ARF4 suppression in the IEC line increased the expression of tight junction
      proteins and decreased intestinal epithelial permeability. These results indicate
      that commensal microbiome-dependent miR-21-5p expression in IECs regulates
      intestinal epithelial permeability via ARF4, which may therefore represent a
      target for preventing or managing dysfunction of the intestinal epithelial
      barrier.

PMID- 28760829
TI  - Trump demands Republicans continue effort to repeal Affordable Care Act.

PMID- 28760828
TI  - An acetylation-phosphorylation switch that regulates tau aggregation propensity
      and function.
AB  - The aberrant accumulation of tau protein is a pathological hallmark of a class of
      neurodegenerative diseases known as tauopathies, including Alzheimer's disease
      and related dementias. On the basis of previous observations that tau is a direct
      substrate of histone deacetylase 6 (HDAC6), we sought to map all HDAC6-responsive
      sites in tau and determine how acetylation in a site-specific manner affects
      tau's biophysical properties in vitro Our findings indicate that several
      acetylation sites in tau are responsive to HDAC6 and that acetylation on Lys-321
      (within a KCGS motif) is both essential for acetylation-mediated inhibition of
      tau aggregation in vitro and a molecular tactic for preventing phosphorylation on
      the downstream Ser-324 residue. To determine the functional consequence of this
      HDAC6-regulated phosphorylation event, we examined tau's ability to promote
      microtubule assembly and found that phosphorylation of Ser-324 interferes with
      the normal microtubule-stabilizing function of tau. Tau phosphorylation of Ser
      324 (pSer-324) has not previously been evaluated in the context of tauopathy, and
      here we observed increased deposition of pSer-324-positive tau both in mouse
      models of tauopathy and in patients with Alzheimer's disease. These findings
      uncover a novel acetylation-phosphorylation switch at Lys-321/Ser-324 that
      coordinately regulates tau polymerization and function. Because the disease
      relevance of this finding is evident, additional studies are needed to examine
      the role of pSer-324 in tau pathobiology and to determine whether therapeutically
      modulating this acetylation-phosphorylation switch affects disease progression in
      vivo.

PMID- 28760830
TI  - Chronic warm exposure impairs growth performance and reduces thermal safety
      margins in the common triplefin fish (Forsterygion lapillum).
AB  - Intertidal fish species face gradual chronic changes in temperature and greater
      extremes of acute thermal exposure through climate-induced warming. As sea
      temperatures rise, it has been proposed that whole-animal performance will be
      impaired through oxygen and capacity limited thermal tolerance [OCLTT; reduced
      aerobic metabolic scope (MS)] and, on acute exposure to high temperatures,
      thermal safety margins may be reduced because of constrained acclimation capacity
      of upper thermal limits. Using the New Zealand triplefin fish (Forsterygion
      lapillum), this study addressed how performance in terms of growth and metabolism
      (MS) and upper thermal tolerance limits would be affected by chronic exposure to
      elevated temperature. Growth was measured in fish acclimated (12 weeks) to
      present and predicted future temperatures and metabolic rates were then
      determined in fish at acclimation temperatures and with acute thermal ramping. In
      agreement with the OCLTT hypothesis, chronic exposure to elevated temperature
      significantly reduced growth performance and MS. However, despite the prospect of
      impaired growth performance under warmer future summertime conditions, an annual
      growth model revealed that elevated temperatures may only shift the timing of
      high growth potential and not the overall annual growth rate. While the upper
      thermal tolerance (i.e. critical thermal maxima) increased with exposure to
      warmer temperatures and was associated with depressed metabolic rates during
      acute thermal ramping, upper thermal tolerance did not differ between present and
      predicted future summertime temperatures. This suggests that warming may
      progressively decrease thermal safety margins for hardy generalist species and
      could limit the available habitat range of intertidal populations.

PMID- 28760831
TI  - A mosquito entomoglyceroporin, Aedes aegypti AQP5, participates in water
      transport across the Malpighian tubules of larvae.
AB  - The mosquito Aedes aegypti is the primary vector for arboviral diseases such as
      Zika fever, dengue fever, chikungunya and yellow fever. The larvae reside in hypo
      osmotic freshwater habitats, where they face dilution of their body fluids from
      osmotic influx of water. The Malpighian tubules help maintain ionic and osmotic
      homeostasis by removing excess water from the hemolymph; however, the
      transcellular pathway for this movement remains unresolved. Aquaporins are
      transmembrane channels thought to permit transcellular transport of water from
      the hemolymph into the Malpighian tubule lumen. Immunolocalization of A.aegypti
      aquaporin 5 (AaAQP5) revealed expression by Malpighian tubule principal cells of
      the larvae, with localization to both the apical and basolateral membranes.
      Knockdown of AaAQP5 with double-stranded RNA decreased larval survival, reduced
      rates of fluid, K+ and Na+ secretion by the Malpighian tubules, and reduced Cl-
      concentrations in the hemolymph. These findings indicate that AaAQP5 participates
      in transcellular water transport across the Malpighian tubules of larval Aaegypti
      where global AaAQP5 expression is important for larval survival.

PMID- 28760827
TI  - Copper homeostasis networks in the bacterium Pseudomonas aeruginosa.
AB  - Bacterial copper (Cu+) homeostasis enables both precise metallation of diverse
      cuproproteins and control of variable metal levels. To this end, protein networks
      mobilize Cu+ to cellular targets with remarkable specificity. However, the
      understanding of these processes is rather fragmented. Here, we use genome-wide
      transcriptomic analysis by RNA-Seq to characterize the response of Pseudomonas
      aeruginosa to external 0.5 mm CuSO4, a condition that did not generate
      pleiotropic effects. Pre-steady-state (5-min) and steady-state (2-h) Cu+ fluxes
      resulted in distinct transcriptome landscapes. Cells quickly responded to Cu2+
      stress by slowing down metabolism. This was restored once steady state was
      reached. Specific Cu+ homeostasis genes were strongly regulated in both
      conditions. Our system-wide analysis revealed induction of three Cu+ efflux
      systems (a P1B-ATPase, a porin, and a resistance-nodulation-division (RND)
      system) and of a putative Cu+-binding periplasmic chaperone and the unusual
      presence of two cytoplasmic CopZ proteins. Both CopZ chaperones could bind Cu+
      with high affinity. Importantly, novel transmembrane transporters probably
      mediating Cu+ influx were among those largely repressed upon Cu+ stress.
      Compartmental Cu+ levels appear independently controlled; the cytoplasmic Cu+
      sensor CueR controls cytoplasmic chaperones and plasma membrane transporters,
      whereas CopR/S responds to periplasmic Cu+ Analysis of DeltacopR and DeltacueR
      mutant strains revealed a CopR regulon composed of genes involved in periplasmic
      Cu+ homeostasis and its putative DNA recognition sequence. In conclusion, our
      study establishes a system-wide model of a network of sensors/regulators, soluble
      chaperones, and influx/efflux transporters that control the Cu+ levels in P.
      aeruginosa compartments.

PMID- 28760832
TI  - Avian thermoregulation in the heat: evaporative cooling capacity of arid-zone
      Caprimulgiformes from two continents.
AB  - Birds in the order Caprimulgiformes (nightjars and allies) have a remarkable
      capacity for thermoregulation over a wide range of environmental temperatures,
      exhibiting pronounced heterothermy in cool conditions and extreme heat tolerance
      at high environmental temperatures. We measured thermoregulatory responses to
      acute heat stress in three species of Caprimulgiformes that nest in areas of
      extreme heat and aridity, the common poorwill (Phalaenoptilus nuttallii:
      Caprimulgidae) and lesser nighthawk (Chordeiles acutipennis: Caprimulgidae) in
      the Sonoran Desert of Arizona, and the Australian owlet-nightjar (Aegotheles
      cristatus: Aegothelidae) in the mallee woodlands of South Australia. We exposed
      wild-caught birds to progressively increasing air temperatures (Ta) and measured
      resting metabolic rate (RMR), evaporative water loss (EWL), body temperature (Tb)
      and heat tolerance limit (HTL; the maximum Ta reached). Comparatively low RMR
      values were observed in all species (0.35, 0.36 and 0.40 W for the poorwill,
      nighthawk and owlet-nightjar, respectively), with Tb approximating Ta at 40
      degrees C and mild hyperthermia occurring as Ta reached the HTL. Nighthawks and
      poorwills reached HTLs of 60 and 62 degrees C, respectively, whereas the owlet
      nightjar had a HTL of 52 degrees C. RMR increased gradually above minima at Ta of
      42, 42 and 35 degrees C, and reached 1.7, 1.9 and 2.0 times minimum resting
      values at HTLs in the poorwill, nighthawk and owlet-nightjar, respectively. EWL
      increased rapidly and linearly as Ta exceeded Tb and resulted in maximum rates of
      evaporative heat dissipation equivalent to 237-424% of metabolic heat production.
      Bouts of gular flutter resulted in large transient increases in evaporative heat
      loss (50-123%) accompanied by only small increments in RMR (<5%). The cavity
      nesting/roosting owlet-nightjar had a lower HTL and less efficient evaporative
      cooling compared with the species that nest and/or roost on open desert surfaces.
      The high efficiency of gular flutter for evaporative cooling, combined with mild
      hyperthermia, provides the physiological basis for defending Tb well below Ta in
      extreme heat and is comparable to the efficient cooling observed in arid-zone
      columbids in which cutaneous EWL is the predominant cooling pathway.

PMID- 28760833
TI  - Measuring quality of end-of-life communication and decision-making: Do we have
      this right?

PMID- 28760834
TI  - Validation of quality indicators for end-of-life communication: results of a
      multicentre survey.
AB  - BACKGROUND: The lack of validated quality indicators is a major barrier to
      improving end-of-life communication and decision-making. We sought to show the
      feasibility of and provide initial validation for a set of quality indicators
      related to end-of-life communication and decision-making. METHODS: We
      administered a questionnaire to patients and their family members in 12 hospitals
      and asked them about advance care planning and goals-of-care discussions.
      Responses were used to calculate a quality indicator score. To validate this
      score, we determined its correlation with the concordance between the patients'
      expressed wishes and the medical order for life-sustaining treatments recorded in
      the hospital chart. We compared the correlation with concordance for the advance
      care planning component score with that for the goal-of-care discussion scores.
      RESULTS: We enrolled 297 patients and 209 family members. At all sites, both
      overall quality indicators and individual domain scores were low and there was
      wide variability around the point estimates. The highest-ranking institution had
      an overall quality indicator score (95% confidence interval) of 40% (36%-44%) and
      the lowest had a score of 18% (11%-25%). There was a strong correlation between
      the overall quality indicator score and the concordance measure (r = 0.72, p =
      0.008); the estimated correlation between the advance care planning score and the
      concordance measure (r = 0.35) was weaker than that between the goal-of-care
      discussion scores and the concordance measure (r = 0.53). INTERPRETATION: Quality
      of end-of-life communication and decision-making appears low overall, with
      considerable variability across hospitals. The proposed quality indicator measure
      shows feasibility and partial validity. Study registration: ClinicalTrials.gov,
      no. NCT01362855.

PMID- 28760835
TI  - Public drug policy for children in Canada.

PMID- 28760837
TI  - Cardiac paraganglioma.

PMID- 28760836
TI  - Medical cannabinoids.

PMID- 28760838
TI  - Optimal levels of DHEA for pregnancy may be reduced by antibiotics.

PMID- 28760839
TI  - The authors respond to: "Optimal levels of DHEA for pregnancy may be reduced by
      antibiotics".

PMID- 28760840
TI  - UK seeks to make DNA testing standard in cancer care.

PMID- 28760841
TI  - CIHR's face-to-face about-face.

PMID- 28760842
TI  - Support grows for paying surrogates.

PMID- 28760843
TI  - Atorvastatin enhances radiosensitivity in hypoxia-induced prostate cancer cells
      related with HIF-1alpha inhibition.
AB  - Hypoxia could enhance radioresistance in prostate cancer cells through up
      regulating HIF-1alpha, which could be inhibited by statins in several cancer
      cells. However, this effect of statins in prostate cancer remains unclear. In the
      present study, we aim to investigate the effect of atorvastatin on HIF-1alpha
      expression and radiosensitivity in prostate cancer cells. The hypoxia-induced
      human prostate cancer PC3 cells were generated by incubating with 5% O2 for 24 h.
      The cell viability and apoptosis were respectively analyzed by cell counting kit
      8 (CCK-8) assay and flow cytometry. The HIF-1alpha protein expression was
      assessed by Western blotting. HIF-1alpha expression in PC3 cells was
      significantly increased after incubating with 5% O2 for 24 h. The viability of
      hypoxia-induced PC3 cells was inhibited by a higher dose of irradiation than
      control cells. The viability of hypoxia-induced PC3 cells were inhibited by
      astorvastatin with a higher concentration than control cells. Astorvastatin
      reduced the HIF-1alpha protein expression in hypoxia-induced PC3 cells, and
      induced apoptosis of both control and hypoxia-induced cells with and without
      irradiation. Atorvastatin could enhance radiosensitivity in hypoxia-induced
      prostate cancer cells, which may be related with inhibition of HIF-1alpha
      protein.

PMID- 28760844
TI  - Inhibitory effect ofquercetinon titaniumparticle-inducedendoplasmic reticulum
      stress (ERS)-related apoptosisandin vivoosteolysis.
AB  - Wear particle-induced periprosthetic osteolysis is the main cause of aseptic
      loosening of orthopaedic implants. The aim of this study is to determine the
      protective effect of quercetin (QUE) against titanium (Ti) particle-induced ERS
      related apoptosis and osteolysis. In this study, RAW264.7 cells were pretreated
      with different concentrations (40, 80, and 160 MUmol/l) of QUE for 30 min and
      then treated with Ti particle (5 mg/ml) for 24 h. Cell viability and apoptosis
      were determined using MTT assay and Annexin V-FITC apoptosis detection kit,
      respectively. Protein and mRNA expressions of ERS-related genes were examined by
      western blot and real-time PCR, respectively. The release of inflammatory
      cytokines was detected by ELISA. Then a mouse calvarial osteolysis model was
      established. Histological sections of calvaria were stained with H&E or TRAP. The
      results showed that Ti particle reduced cell viability and induced apoptosis in
      RAW264.7 macrophages. The cytotoxic effects of Ti particle were dramatically
      inhibited by QUE pretreatment. Interestingly, we found that QUE also
      significantly reduced Ti particle-induced up-regulation of the expression levels
      of PERK, IRE1, GRP78, CHOP, caspase-12 and caspase-3 and enhanced the down
      regulation of Bcl-2. In addition, QUE decreased Ti particle-induced inflammatory
      cytokines release from RAW264.7 cells. Moreover, treatment with QUE markedly
      decreased osteoclast number. In a mouse calvarial osteolysis model, QUE inhibited
      Ti particle-induced osteolysis in vivo by inhibiting osteoclast formation and
      expressions of ERS-related genes. In conclusion, QUE can protect RAW264.7 cells
      from Ti particle-induced ERS-related apoptosis and suppress calvarial osteolysis
      in vivo.

PMID- 28760845
TI  - MicroRNA-98 interferes with thrombospondin 1 expression in peripheral B cells of
      patients with asthma.
AB  - Thrombospondin 1 (TSP1)-producing B cells are an important immune regulatory cell
      fraction in the body, which are compromised in a number of immune diseases. miRs
      are involved in the immune regulation. The present study aims to elucidate the
      mechanism by which miR-98 interferes with the expression of TSP1 in B cells of
      the peripheral blood system. In the present study, peripheral blood samples were
      collected from patients with allergic asthma. The B cells were isolated from the
      blood samples to be analyzed for the expression of miR-98 and TSP1. The results
      showed that the levels of miR-98 were higher, the levels of TSP1 were lower, in B
      cells isolated from the peripheral blood in patients with asthma. A negative
      correlation was identified between the data of miR-98 and TSP1 in B cells.
      Exposure to T helper (Th) 2 (Th2) cytokine, interleukin (IL)-13, increased the
      expression of miR-98 and suppressed the expression of TSP1 in peripheral B cells,
      which was abolished by knocking down the miR-98 gene. In conclusion, miR-98 can
      suppress the expression of TSP1 in the peripheral B cells of patients with
      allergic asthma.

PMID- 28760846
TI  - Conformational Changes That Coordinate the Activity of BamA and BamD Allowing
      beta-Barrel Assembly.
AB  - Most integral outer membrane proteins (OMPs) of Gram-negative bacteria, such as
      Escherichia coli, assume a beta-barrel structure. The beta-barrel assembly
      machine (Bam), a five-member complex composed of beta-barrel OMP BamA and four
      associated lipoproteins, BamB, BamC, BamD, and BamE, folds and inserts OMPs into
      the outer membrane. The two essential proteins BamA and BamD interact to
      stabilize two subcomplexes, BamAB and BamCDE, and genetic and structural evidence
      suggests that interactions between BamA and BamD occur via an electrostatic
      interaction between a conserved aspartate residue in a periplasmic domain of BamA
      and a conserved arginine in BamD. In this work, we characterize charge-change
      mutations at these key BamA and BamD residues and nearby charged residues in BamA
      with respect to OMP assembly and Bam complex stability. We show that Bam complex
      stability does not correlate with function, that BamA and BamD must adopt at
      least two active conformational states during OMP assembly, and that these
      charged residues are not required for function. Rather, these charged residues
      are important for coordinating the activities of BamA and BamD to allow efficient
      OMP assembly. We present a model of OMP assembly wherein recognition and binding
      of unfolded OMP substrate by BamA and BamD induce a signaling interaction between
      the two proteins, causing conformational changes necessary for the assembly
      reaction to proceed. By analogy to signal sequence recognition by SecYEG, we
      believe these BamA-BamD interactions ensure that both substrate and complex are
      competent for OMP assembly before the assembly reaction commences.IMPORTANCE
      Conformational changes in the proteins of the beta-barrel assembly machine (Bam
      complex) are associated with the folding and assembly of outer membrane proteins
      (OMPs) in Gram-negative bacteria. We show that electrostatic interactions between
      the two essential proteins BamA and BamD coordinate conformational changes upon
      binding of unfolded substrate that allow the assembly reaction to proceed.
      Mutations affecting this interaction are lethal not because they destabilize the
      Bam complex but rather because they disrupt this coordination. Our model of BamA
      BamD interactions regulating conformation in response to proper substrate
      interaction is reminiscent of conformational changes the secretory (Sec)
      machinery undergoes after signal sequence recognition that ensure protein quality
      control.

PMID- 28760847
TI  - TetR Family Transcriptional Regulator PccD Negatively Controls Propionyl Coenzyme
      A Assimilation in Saccharopolyspora erythraea.
AB  - Propanol stimulates erythromycin biosynthesis by increasing the supply of
      propionyl coenzyme A (propionyl-CoA), a starter unit of erythromycin production
      in Saccharopolyspora erythraea Propionyl-CoA is assimilated via propionyl-CoA
      carboxylase to methylmalonyl-CoA, an extender unit of erythromycin. We found that
      the addition of n-propanol or propionate caused a 4- to 16-fold increase in the
      transcriptional levels of the SACE_3398-3400 locus encoding propionyl-CoA
      carboxylase, a key enzyme in propionate metabolism. The regulator PccD was proved
      to be directly involved in the transcription regulation of the SACE_3398-3400
      locus by EMSA and DNase I footprint analysis. The transcriptional levels of
      SACE_3398-3400 were upregulated 15- to 37-fold in the pccD gene deletion strain
      (DeltapccD) and downregulated 3-fold in the pccD overexpression strain (WT/pIB
      pccD), indicating that PccD was a negative transcriptional regulator of SACE_3398
      3400. The DeltapccD strain has a higher growth rate than that of the wild-type
      strain (WT) on Evans medium with propionate as the sole carbon source, whereas
      the growth of the WT/pIB-pccD strain was repressed. As a possible metabolite of
      propionate metabolism, methylmalonic acid was identified as an effector molecule
      of PccD and repressed its regulatory activity. A higher level of erythromycin in
      the DeltapccD strain was observed compared with that in the wild-type strain. Our
      study reveals a regulatory mechanism in propionate metabolism and suggests new
      possibilities for designing metabolic engineering to increase erythromycin
      yield.IMPORTANCE Our work has identified the novel regulator PccD that controls
      the expression of the gene for propionyl-CoA carboxylase, a key enzyme in
      propionyl-CoA assimilation in S. erythraea PccD represses the generation of
      methylmalonyl-CoA through carboxylation of propionyl-CoA and reveals an effect on
      biosynthesis of erythromycin. This finding provides novel insight into propionyl
      CoA assimilation, and extends our understanding of the regulatory mechanisms
      underlying the biosynthesis of erythromycin.

PMID- 28760848
TI  - Comprehensive arrayed transposon mutant library of Klebsiella pneumoniae outbreak
      strain KPNIH1.
AB  - Klebsiella pneumoniae and other carbapenem-resistant Enterobacteriaceae are a
      major cause of hospital-acquired infections, yet the basis of their success as
      nosocomial pathogens is poorly understood. To help provide a foundation for
      genetic analysis of K. pneumoniae, we created an arrayed, sequence-defined
      transposon mutant library of an isolate from the 2011 outbreak of infections at
      the U.S. National Institutes of Health Clinical Center. The library is made up of
      12,000 individually arrayed mutants of a carbapenemase deletion parent strain and
      provides coverage of 85% of predicted genes. The library includes an average of
      2.5 mutants per gene, with most insertion locations identified and confirmed in
      two independent rounds of Sanger sequencing. Based on an independent Tn-seq
      assay, about half of the genes lacking representatives in this "two-allele"
      library are essential for growth on nutrient agar. To validate the use of the
      library for phenotyping, we screened candidate mutants for increased antibiotic
      sensitivity using custom phenotypic microarray plates. The screen identified
      several mutations increasing sensitivity to beta-lactams (in acrB1, mcrB, ompR,
      phoP1 and slt1), and found that two-component regulator cpxAR mutations increased
      multiple sensitivities (to an aminoglycoside, a fluoroquinolone and several beta
      lactams). Strains making up the two-allele mutant library are available through a
      web-based request mechanism.IMPORTANCEK. pneumoniae and other carbapenem
      resistant Enterobacteriaceae are recognized as a top public health threat by the
      Centers for Disease Control. The analysis of these major nosocomial pathogens has
      been limited by the experimental resources available for studying them. The work
      presented here describes a sequence-defined mutant library for a K. pneumoniae
      strain (KPNIH1) which represents an attractive model for studies of this pathogen
      because it is a recent isolate of the major sequence type that causes infection,
      the epidemiology of the outbreak it caused is well-characterized, and an
      annotated genome sequence is available. The ready availability of defined mutants
      for nearly all nonessential genes of the model strain should facilitate the
      genetic dissection of complex traits like pathogenesis and antibiotic resistance.

PMID- 28760849
TI  - Stability of Proteins Out of Service: the GapB Case of Bacillus subtilis.
AB  - Bacillus subtilis possesses two glyceraldehyde-3-phosphate dehydrogenases with
      opposite roles, the glycolytic NAD-dependent GapA and the NADP-dependent GapB
      enzyme, which is exclusively required during gluconeogenesis but not active under
      conditions promoting glycolysis. We propose that proteins that are no longer
      needed will be recognized and proteolyzed by Clp proteases and thereby recycled.
      To test this postulation, we analyzed the stability of the glycolytic enzyme GapA
      and the gluconeogenetic enzyme GapB in the presence and absence of glucose. It
      turned out that GapA remained rather stable under both glycolytic and
      gluconeogenetic conditions. In contrast, the gluconeogenetic enzyme GapB was
      degraded after a shift from malate to glucose (i.e., from gluconeogenesis to
      glycolysis), displaying an estimated half-life of approximately 3 h. Comparative
      in vivo pulse-chase labeling and immunoprecipitation experiments of the wild-type
      strain and isogenic mutants identified the ATP-dependent ClpCP protease as the
      enzyme responsible for the degradation of GapB. However, arginine protein
      phosphorylation, which was recently described as a general tagging mechanism for
      protein degradation, did not seem to play a role in GapB proteolysis, because
      GapB was also degraded in a mcsB mutant, lacking arginine kinase, in the same
      manner as in the wild type.IMPORTANCE GapB, the NADP-dependent glyceraldehyde-3
      phosphosphate dehydrogenase, is essential for B. subtilis under gluconeogenetic
      conditions. However, after a shift to glycolytic conditions, GapB loses its
      physiological function within the cell and becomes susceptible to degradation, in
      contrast to GapA, the glycolytic NAD-dependent glyceraldehyde-3-phosphate
      dehydrogenase, which remains stable under glycolytic and gluconeogenetic
      conditions. Subsequently, GapB is proteolyzed in a ClpCP-dependent manner.
      According to our data, the arginine kinase McsB is not involved as adaptor
      protein in this process. ClpCP appears to be in charge in the removal of
      inoperable enzymes in B. subtilis, which is a strictly regulated process in which
      the precise recognition mechanism(s) remains to be identified.

PMID- 28760852
TI  - Stress Reduction, Bacterial Style.
AB  - Bacteria have robust responses to a variety of stresses. In particular, bacteria
      like Escherichia coli have multiple cell envelope stress responses, and generally
      we evaluate what these responses are doing by the repair systems they induce.
      However, probably at least as important in interpreting what is being sensed as
      stress are the genes that these stress systems downregulate, directly or
      indirectly. This is discussed here for the Cpx and sigma E systems of E. coli.

PMID- 28760851
TI  - A Bacterial Stress Response Regulates Respiratory Protein Complexes To Control
      Envelope Stress Adaptation.
AB  - The Cpx envelope stress response mediates adaptation to stresses that affect
      protein folding within the envelope of Gram-negative bacteria. Recent
      transcriptome analyses revealed that the Cpx response impacts genes that affect
      multiple cellular functions predominantly associated with the cytoplasmic
      membrane. In this study, we examined the connection between the Cpx response and
      the respiratory complexes NADH dehydrogenase I and cytochrome bo3 in
      enteropathogenic Escherichia coli We found that the Cpx response directly
      represses the transcription of the nuo and cyo operons and that Cpx-mediated
      repression of these complexes confers adaptation to stresses that compromise
      envelope integrity. Furthermore, we found that the activity of the aerobic
      electron transport chain is reduced in E. coli lacking a functional Cpx response
      despite no change in the transcription of either the nuo or the cyo operon.
      Finally, we show that expression of NADH dehydrogenase I and cytochrome bo3
      contributes to basal Cpx pathway activity and that overproduction of individual
      subunits can influence pathway activation. Our results demonstrate that the Cpx
      response gauges and adjusts the expression, and possibly the function, of inner
      membrane protein complexes to enable adaptation to envelope stress.IMPORTANCE
      Bacterial stress responses allow microbes to survive environmental transitions
      and conditions, such as those encountered during infection and colonization, that
      would otherwise kill them. Enteric microbes that inhabit or infect the gut are
      exposed to a plethora of stresses, including changes in pH, nutrient composition,
      and the presence of other bacteria and toxic compounds. Bacteria detect and adapt
      to many of these conditions by using envelope stress responses that measure the
      presence of stressors in the outermost compartment of the bacterium by monitoring
      its physiology. The Cpx envelope stress response plays a role in antibiotic
      resistance and host colonization, and we have shown that it regulates many
      functions at the bacterial inner membrane. In this report, we describe a novel
      role for the Cpx response in sensing and controlling the expression of large,
      multiprotein respiratory complexes at the cytoplasmic membrane of Escherichia
      coli The significance of our research is that it will increase our understanding
      of how these stress responses are involved in antibiotic resistance and the
      mechanisms used by bacteria to colonize the gut.

PMID- 28760853
TI  - Survival of Head and Neck Cancer Cells Relies upon LZK Kinase-Mediated
      Stabilization of Mutant p53.
AB  - Head and neck squamous cell carcinoma (HNSCC) includes epithelial cancers of the
      oral and nasal cavity, larynx, and pharynx and accounts for ~350,000 deaths per
      year worldwide. Smoking-related HNSCC is associated with few targetable mutations
      but is defined by frequent copy-number alteration, the most common of which is
      gain at 3q. Critical 3q target genes have not been conclusively determined for
      HNSCC. Here, we present data indicating that MAP3K13 (encoding LZK) is an
      amplified driver gene in HNSCC. Copy-number gain at 3q resulted in increased
      MAP3K13 mRNA in HNSCC tumor samples and cell lines. Silencing LZK reduced cell
      viability and proliferation of HNSCC cells with 3q gain but not control cell
      lines. Inducible silencing of LZK caused near-complete loss of colony-forming
      ability in cells harboring 3q gain. These results were validated in vivo by
      evidence that LZK silencing was sufficient to reduce tumor growth in a xenograft
      model of HNSCC. Our results establish LZK as critical for maintaining expression
      of mutant stabilized p53. Cancer Res; 77(18); 4961-72. (c)2017 AACR.

PMID- 28760850
TI  - Regulation of the Locus of Enterocyte Effacement in Attaching and Effacing
      Pathogens.
AB  - Attaching and effacing (AE) pathogens colonize the gut mucosa using a type three
      secretion system (T3SS) and a suite of effector proteins. The locus of enterocyte
      effacement (LEE) is the defining genetic feature of the AE pathogens, encoding
      the T3SS and the core effector proteins necessary for pathogenesis. Extensive
      research has revealed a complex regulatory network that senses and responds to a
      myriad of host- and microbiota-derived signals in the infected gut to control
      transcription of the LEE. These signals include microbiota-liberated sugars and
      metabolites in the gut lumen, molecular oxygen at the gut epithelium, and host
      hormones. Recent research has revealed that AE pathogens also recognize physical
      signals, such as attachment to the epithelium, and that the act of effector
      translocation remodels gene expression in infecting bacteria. In this review, we
      summarize our knowledge to date and present an integrated view of how chemical,
      geographical, and physical cues regulate the virulence program of AE pathogens
      during infection.

PMID- 28760854
TI  - Oncogenic KRAS and p53 Loss Drive Gastric Tumorigenesis in Mice That Can Be
      Attenuated by E-Cadherin Expression.
AB  - Gastric adenocarcinoma is the third leading cause of cancer-related death
      worldwide, but no models exist to readily investigate distant metastases that are
      mainly responsible for mortality in this disease. Here we report the development
      of a genetically engineered mouse model of gastric adenocarcinoma tumorigenesis
      based on KrasG12D expression plus inactivation of E-cadherin (Cdh1) and p53 in
      the gastric parietal cell lineage. Intestinal and diffuse gastric tumors arise
      rapidly in this model that displays a median survival of 76 days. Tumors occur
      throughout the stomach, with metastases documented in lymph nodes, lung, and
      liver. Mice otherwise identical but retaining one wild-type Cdh1 allele exhibited
      longer survival with only 20% penetrance of invasive tumors and no apparent lung
      or liver metastases. Notably, increased RAS activity and downstream MAPK
      signaling was observed in stomachs only when E-cadherin was absent. This model
      offers a valuable tool to investigate gastric adenocarcinoma subtypes where
      RAS/MAPK pathway activation and E-cadherin attenuation are common. Cancer Res;
      77(19); 5349-59. (c)2017 AACR.

PMID- 28760855
TI  - Dual Targeting of Insulin Receptor and KIT in Imatinib-Resistant Gastrointestinal
      Stromal Tumors.
AB  - Oncogenic KIT or PDGFRA receptor tyrosine kinase (RTK) mutations are compelling
      therapeutic targets in gastrointestinal stromal tumors (GIST), and treatment with
      the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with
      metastatic GIST. Most GISTs eventually acquire imatinib resistance due to
      secondary mutations in the KIT kinase domain, but it is unclear whether these
      genomic resistance mechanisms require other cellular adaptations to create a
      clinically meaningful imatinib-resistant state. Using phospho-RTK and immunoblot
      assays, we demonstrate activation of KIT and insulin receptor (IR) in imatinib
      resistant GIST cell lines (GIST430 and GIST48) and biopsies with acquisition of
      KIT secondary mutations, but not in imatinib-sensitive GIST cells (GIST882 and
      GIST-T1). Treatment with linsitinib, a specific IR inhibitor, inhibited IR and
      downstream intermediates AKT, MAPK, and S6 in GIST430 and GIST48, but not in
      GIST882, exerting minimal effect on KIT phosphorylation in these cell lines.
      Additive effects showing increased apoptosis, antiproliferative effects, cell
      cycle arrest, and decreased pAKT and pS6 expression, tumor growth, migration, and
      invasiveness were observed in imatinib-resistant GIST cells with IR activation
      after coordinated inhibition of IR and KIT by linsitinib (or IR shRNA) and
      imatinib, respectively, compared with either intervention alone. IGF2
      overexpression was responsible for IR activation in imatinib-resistant GIST
      cells, whereas IR activation did not result from IR amplification, IR mutation,
      or KIT phosphorylation. Our findings suggest that combinatorial inhibition of IR
      and KIT warrants clinical evaluation as a novel therapeutic strategy in imatinib
      resistant GISTs. Cancer Res; 77(18); 5107-17. (c)2017 AACR.

PMID- 28760856
TI  - Normal and Malignant Cells Exhibit Differential Responses to Calcium
      Electroporation.
AB  - Calcium electroporation may offer a simple general tool for anticancer therapy.
      Transient permeabilization of cancer cell membranes created by applying short,
      high-voltage pulses in tumors enables high calcium influxes that trigger cell
      death. In this study, we compared the relative sensitivity of different human
      tumor models and normal tissues to calcium electroporation. Plasma membrane Ca2+
      ATPase (PMCA) protein expression was confirmed in vitro in all cancer cell lines
      and normal primary dermal fibroblasts studied. In all tumor types tested in vivo,
      calcium electroporation effectively induced necrosis, with a range of
      sensitivities observed (36%-88%) 2 days after treatment. Necrosis was induced
      using calcium concentrations of 100-500 mmol/L and injection volumes 20%-80% of
      tumor volume. Notably, only limited effects were seen in normal tissue. Calcium
      content increased >7-fold in tumor and skin tissue after calcium electroporation
      but decreased in skin tissue 4 hours after treatment to levels comparable with
      untreated controls, whereas calcium content endured at high levels in tumor
      tissue. Mechanistic experiments in vitro indicated that calcium influx was
      similar in fibroblasts and cancer cells. However, we observed decreased PMCA
      expression in cancer cells compared with fibroblasts, offering a potential
      explanation for the different calcium content in tumor cells versus normal
      tissues. Overall, our results suggest that calcium electroporation can elicit a
      rapid and selective necrosis of solid tumors, with limited deleterious effects on
      surrounding normal tissues. Cancer Res; 77(16); 4389-401. (c)2017 AACR.

PMID- 28760857
TI  - FBW7 Loss Promotes Chromosomal Instability and Tumorigenesis via Cyclin E1/CDK2
      Mediated Phosphorylation of CENP-A.
AB  - The centromere regulates proper chromosome segregation, and its dysfunction is
      implicated in chromosomal instability (CIN). However, relatively little is known
      about how centromere dysfunction occurs in cancer. Here, we define the
      consequences of phosphorylation by cyclin E1/CDK2 on a conserved Ser18 residue of
      centromere-associated protein CENP-A, an essential histone H3 variant that
      specifies centromere identity. Ser18 hyperphosphorylation in cells occurred upon
      loss of FBW7, a tumor suppressor whose inactivation leads to CIN. This event on
      CENP-A reduced its centromeric localization, increased CIN, and promoted
      anchorage-independent growth and xenograft tumor formation. Overall, our results
      revealed a pathway that cyclin E1/CDK2 activation coupled with FBW7 loss promotes
      CIN and tumor progression via CENP-A-mediated centromere dysfunction. Cancer Res;
      77(18); 4881-93. (c)2017 AACR.

PMID- 28760858
TI  - Segregation of Visual Response Properties in the Mouse Superior Colliculus and
      Their Modulation during Locomotion.
AB  - The superior colliculus (SC) receives direct input from the retina and integrates
      it with information about sound, touch, and state of the animal that is relayed
      from other parts of the brain to initiate specific behavioral outcomes. The
      superficial SC layers (sSC) contain cells that respond to visual stimuli, whereas
      the deep SC layers (dSC) contain cells that also respond to auditory and
      somatosensory stimuli. Here, we used a large-scale silicon probe recording system
      to examine the visual response properties of SC cells of head-fixed and alert
      male mice. We found cells with diverse response properties including: (1)
      orientation/direction-selective (OS/DS) cells with a firing rate that is
      suppressed by drifting sinusoidal gratings (negative OS/DS cells); (2) suppressed
      by-contrast cells; (3) cells with complex-like spatial summation nonlinearity;
      and (4) cells with Y-like spatial summation nonlinearity. We also found specific
      response properties that are enriched in different depths of the SC. The sSC is
      enriched with cells with small RFs, high evoked firing rates (FRs), and sustained
      temporal responses, whereas the dSC is enriched with the negative OS/DS cells and
      with cells with large RFs, low evoked FRs, and transient temporal responses.
      Locomotion modulates the activity of the SC cells both additively and
      multiplicatively and changes the preferred spatial frequency of some SC cells.
      These results provide the first description of the negative OS/DS cells and
      demonstrate that the SC segregates cells with different response properties and
      that the behavioral state of a mouse affects SC activity.SIGNIFICANCE STATEMENT
      The superior colliculus (SC) receives visual input from the retina in its
      superficial layers (sSC) and induces eye/head-orientating movements and innate
      defensive responses in its deeper layers (dSC). Despite their importance, very
      little is known about the visual response properties of dSC neurons. Using high
      density electrode recordings and novel model-based analysis, we found several
      novel visual response properties of the SC cells, including encoding of a cell's
      preferred orientation or direction by suppression of the firing rate. The sSC and
      the dSC are enriched with cells with different visual response properties.
      Locomotion modulates the cells in the SC. These findings contribute to our
      understanding of how the SC processes visual inputs, a critical step in
      comprehending visually guided behaviors.

PMID- 28760860
TI  - On the Structure of Cortical Microcircuits Inferred from Small Sample Sizes.
AB  - The structure in cortical microcircuits deviates from what would be expected in a
      purely random network, which has been seen as evidence of clustering. To address
      this issue, we sought to reproduce the nonrandom features of cortical circuits by
      considering several distinct classes of network topology, including clustered
      networks, networks with distance-dependent connectivity, and those with broad
      degree distributions. To our surprise, we found that all of these qualitatively
      distinct topologies could account equally well for all reported nonrandom
      features despite being easily distinguishable from one another at the network
      level. This apparent paradox was a consequence of estimating network properties
      given only small sample sizes. In other words, networks that differ markedly in
      their global structure can look quite similar locally. This makes inferring
      network structure from small sample sizes, a necessity given the technical
      difficulty inherent in simultaneous intracellular recordings, problematic. We
      found that a network statistic called the sample degree correlation (SDC)
      overcomes this difficulty. The SDC depends only on parameters that can be
      estimated reliably given small sample sizes and is an accurate fingerprint of
      every topological family. We applied the SDC criterion to data from rat visual
      and somatosensory cortex and discovered that the connectivity was not consistent
      with any of these main topological classes. However, we were able to fit the
      experimental data with a more general network class, of which all previous
      topologies were special cases. The resulting network topology could be
      interpreted as a combination of physical spatial dependence and nonspatial,
      hierarchical clustering.SIGNIFICANCE STATEMENT The connectivity of cortical
      microcircuits exhibits features that are inconsistent with a simple random
      network. Here, we show that several classes of network models can account for
      this nonrandom structure despite qualitative differences in their global
      properties. This apparent paradox is a consequence of the small numbers of
      simultaneously recorded neurons in experiment: when inferred via small sample
      sizes, many networks may be indistinguishable despite being globally distinct. We
      develop a connectivity measure that successfully classifies networks even when
      estimated locally with a few neurons at a time. We show that data from rat cortex
      is consistent with a network in which the likelihood of a connection between
      neurons depends on spatial distance and on nonspatial, asymmetric clustering.

PMID- 28760859
TI  - Sound-Evoked Activity Influences Myelination of Brainstem Axons in the Trapezoid
      Body.
AB  - Plasticity of myelination represents a mechanism to tune the flow of information
      by balancing functional requirements with metabolic and spatial constraints. The
      auditory system is heavily myelinated and operates at the upper limits of action
      potential generation frequency and speed observed in the mammalian CNS. This
      study aimed to characterize the development of myelin within the trapezoid body,
      a central auditory fiber tract, and determine the influence sensory experience
      has on this process in mice of both sexes. We find that in vitro conduction speed
      doubles following hearing onset and the ability to support high-frequency firing
      increases concurrently. Also in this time, the diameter of trapezoid body axons
      and the thickness of myelin double, reaching mature-like thickness between 25 and
      35 d of age. Earplugs were used to induce ~50 dB elevation in auditory
      thresholds. If introduced at hearing onset, trapezoid body fibers developed
      thinner axons and myelin than age-matched controls. If plugged during adulthood,
      the thickest trapezoid body fibers also showed a decrease in myelin. These data
      demonstrate the need for sensory activity in both development and maintenance of
      myelin and have important implications in the study of myelin plasticity and how
      this could relate to sensorineural hearing loss following peripheral
      impairment.SIGNIFICANCE STATEMENT The auditory system has many mechanisms to
      maximize the dynamic range of its afferent fibers, which operate at the
      physiological limit of action potential generation, precision, and speed. In this
      study we demonstrate for the first time that changes in peripheral activity
      modifies the thickness of myelin in sensory neurons, not only in development but
      also in mature animals. The current study suggests that changes in CNS
      myelination occur as a downstream mechanism following peripheral deficit. Given
      the required submillisecond temporal precision for binaural auditory processing,
      reduced myelination might augment sensorineural hearing impairment.

PMID- 28760861
TI  - Feedback Inhibition Shapes Emergent Computational Properties of Cortical
      Microcircuit Motifs.
AB  - Cortical microcircuits are very complex networks, but they are composed of a
      relatively small number of stereotypical motifs. Hence, one strategy for throwing
      light on the computational function of cortical microcircuits is to analyze
      emergent computational properties of these stereotypical microcircuit motifs. We
      are addressing here the question how spike timing-dependent plasticity shapes the
      computational properties of one motif that has frequently been studied
      experimentally: interconnected populations of pyramidal cells and parvalbumin
      positive inhibitory cells in layer 2/3. Experimental studies suggest that these
      inhibitory neurons exert some form of divisive inhibition on the pyramidal cells.
      We show that this data-based form of feedback inhibition, which is softer than
      that of winner-take-all models that are commonly considered in theoretical
      analyses, contributes to the emergence of an important computational function
      through spike timing-dependent plasticity: The capability to disentangle
      superimposed firing patterns in upstream networks, and to represent their
      information content through a sparse assembly code.SIGNIFICANCE STATEMENT We
      analyze emergent computational properties of a ubiquitous cortical microcircuit
      motif: populations of pyramidal cells that are densely interconnected with
      inhibitory neurons. Simulations of this model predict that sparse assembly codes
      emerge in this microcircuit motif under spike timing-dependent plasticity.
      Furthermore, we show that different assemblies will represent different hidden
      sources of upstream firing activity. Hence, we propose that spike timing
      dependent plasticity enables this microcircuit motif to perform a fundamental
      computational operation on neural activity patterns.

PMID- 28760862
TI  - Myelinogenic Plasticity of Oligodendrocyte Precursor Cells following Spinal Cord
      Contusion Injury.
AB  - Spontaneous remyelination occurs after spinal cord injury (SCI), but the extent
      of myelin repair and identity of the cells responsible remain incompletely
      understood and contentious. We assessed the cellular origin of new myelin by fate
      mapping platelet-derived growth factor receptor alpha (PDGFRalpha), Olig2+, and
      P0+ cells following contusion SCI in mice. Oligodendrocyte precursor cells (OPCs;
      PDGFRalpha+) produced oligodendrocytes responsible for de novo ensheathment of
      ~30% of myelinated spinal axons at injury epicenter 3 months after SCI,
      demonstrating that these resident cells are a major contributor to
      oligodendrocyte regeneration. OPCs also produced the majority of myelinating
      Schwann cells in the injured spinal cord; invasion of peripheral myelinating
      (P0+) Schwann cells made only a limited contribution. These findings reveal that
      PDGFRalpha+ cells perform diverse roles in CNS repair, as multipotential
      progenitors that generate both classes of myelinating cells. This endogenous
      repair might be exploited as a therapeutic target for CNS trauma and
      disease.SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to profound
      functional deficits, though substantial numbers of axons often survive. One
      possible explanation for these deficits is loss of myelin, creating conduction
      block at the site of injury. SCI leads to oligodendrocyte death and
      demyelination, and clinical trials have tested glial transplants to promote
      myelin repair. However, the degree and duration of myelin loss, and the extent
      and mechanisms of endogenous repair, have been contentious issues. Here, we use
      genetic fate mapping to demonstrate that spontaneous myelin repair by endogenous
      oligodendrocyte precursors is much more robust than previously recognized. These
      findings are relevant to many types of CNS pathology, raising the possibility
      that CNS precursors could be manipulated to repair myelin in lieu of glial
      transplantation.

PMID- 28760864
TI  - Reconfiguration of Brain Network Architectures between Resting-State and
      Complexity-Dependent Cognitive Reasoning.
AB  - Our capacity for higher cognitive reasoning has a measurable limit. This limit is
      thought to arise from the brain's capacity to flexibly reconfigure interactions
      between spatially distributed networks. Recent work, however, has suggested that
      reconfigurations of task-related networks are modest when compared with intrinsic
      "resting-state" network architecture. Here we combined resting-state and task
      driven functional magnetic resonance imaging to examine how flexible, task
      specific reconfigurations associated with increasing reasoning demands are
      integrated within a stable intrinsic brain topology. Human participants (21 males
      and 28 females) underwent an initial resting-state scan, followed by a cognitive
      reasoning task involving different levels of complexity, followed by a second
      resting-state scan. The reasoning task required participants to deduce the
      identity of a missing element in a 4 * 4 matrix, and item difficulty was scaled
      parametrically as determined by relational complexity theory. Analyses revealed
      that external task engagement was characterized by a significant change in
      functional brain modules. Specifically, resting-state and null-task demand
      conditions were associated with more segregated brain-network topology, whereas
      increases in reasoning complexity resulted in merging of resting-state modules.
      Further increments in task complexity did not change the established modular
      architecture, but affected selective patterns of connectivity between
      frontoparietal, subcortical, cingulo-opercular, and default-mode networks. Larger
      increases in network efficiency within the newly established task modules were
      associated with higher reasoning accuracy. Our results shed light on the network
      architectures that underlie external task engagement, and highlight selective
      changes in brain connectivity supporting increases in task
      complexity.SIGNIFICANCE STATEMENT Humans have clear limits in their ability to
      solve complex reasoning problems. It is thought that such limitations arise from
      flexible, moment-to-moment reconfigurations of functional brain networks. It is
      less clear how such task-driven adaptive changes in connectivity relate to
      stable, intrinsic networks of the brain and behavioral performance. We found that
      increased reasoning demands rely on selective patterns of connectivity within
      cortical networks that emerged in addition to a more general, task-induced
      modular architecture. This task-driven architecture reverted to a more segregated
      resting-state architecture both immediately before and after the task. These
      findings reveal how flexibility in human brain networks is integral to achieving
      successful reasoning performance across different levels of cognitive demand.

PMID- 28760863
TI  - Acute Increases in Protein O-GlcNAcylation Dampen Epileptiform Activity in
      Hippocampus.
AB  - O-GlcNAcylation is a ubiquitous and dynamic post-translational modification
      involving the O-linkage of beta-N-acetylglucosamine to serine/threonine residues
      of membrane, cytosolic, and nuclear proteins. This modification is similar to
      phosphorylation and regarded as a key regulator of cell survival and homeostasis.
      Previous studies have shown that phosphorylation of serine residues on synaptic
      proteins is a major regulator of synaptic strength and long-term plasticity,
      suggesting that O-GlcNAcylation of synaptic proteins is likely as important as
      phosphorylation; however, few studies have investigated its role in synaptic
      efficacy. We recently demonstrated that acutely increasing O-GlcNAcylation
      induces a novel form of LTD at CA3-CA1 synapses, O-GlcNAc LTD. Here, using
      hippocampal slices from young adult male rats and mice, we report that
      epileptiform activity at CA3-CA1 synapses, generated by GABAAR inhibition, is
      significantly attenuated when protein O-GlcNAcylation is pharmacologically
      increased. This dampening effect is lost in slices from GluA2 KO mice, indicating
      a requirement of GluA2-containing AMPARs, similar to expression of O-GlcNAc LTD.
      Furthermore, we find that increasing O-GlcNAcylation decreases spontaneous CA3
      pyramidal cell activity under basal and hyperexcitable conditions. This dampening
      effect was also observed on cortical hyperexcitability during in vivo EEG
      recordings in awake mice where the effects of the proconvulsant
      pentylenetetrazole are attenuated by acutely increasing O-GlcNAcylation.
      Collectively, these data demonstrate that the post-translational modification, O
      GlcNAcylation, is a novel mechanism by which neuronal and synaptic excitability
      can be regulated, and suggest the possibility that increasing O-GlcNAcylation
      could be a novel therapeutic target to treat seizure disorders and
      epilepsy.SIGNIFICANCE STATEMENT We recently reported that an acute
      pharmacological increase in protein O-GlcNAcylation induces a novel form of long
      term synaptic depression at hippocampal CA3-CA1 synapses (O-GlcNAc LTD). This
      synaptic dampening effect on glutamatergic networks suggests that increasing O
      GlcNAcylation will depress pathological hyperexcitability. Using in vitro and in
      vivo models of epileptiform activity, we show that acutely increasing O-GlcNAc
      levels can significantly attenuate ongoing epileptiform activity and
      prophylactically dampen subsequent seizure activity. Together, our findings
      support the conclusion that protein O-GlcNAcylation is a regulator of neuronal
      excitability, and it represents a promising target for further research on
      seizure disorder therapeutics.

PMID- 28760865
TI  - Dystroglycan Maintains Inner Limiting Membrane Integrity to Coordinate Retinal
      Development.
AB  - Proper neural circuit formation requires the precise regulation of neuronal
      migration, axon guidance, and dendritic arborization. Mutations affecting the
      function of the transmembrane glycoprotein dystroglycan cause a form of
      congenital muscular dystrophy that is frequently associated with
      neurodevelopmental abnormalities. Despite its importance in brain development,
      the role of dystroglycan in regulating retinal development remains poorly
      understood. Using a mouse model of dystroglycanopathy (ISPDL79* ) and conditional
      dystroglycan mutants of both sexes, we show that dystroglycan is critical for the
      proper migration, axon guidance, and dendritic stratification of neurons in the
      inner retina. Using genetic approaches, we show that dystroglycan functions in
      neuroepithelial cells as an extracellular scaffold to maintain the integrity of
      the retinal inner limiting membrane. Surprisingly, despite the profound
      disruptions in inner retinal circuit formation, spontaneous retinal activity is
      preserved. These results highlight the importance of dystroglycan in coordinating
      multiple aspects of retinal development.SIGNIFICANCE STATEMENT The extracellular
      environment plays a critical role in coordinating neuronal migration and neurite
      outgrowth during neural circuit development. The transmembrane glycoprotein
      dystroglycan functions as a receptor for multiple extracellular matrix proteins
      and its dysfunction leads to a form of muscular dystrophy frequently associated
      with neurodevelopmental defects. Our results demonstrate that dystroglycan is
      required for maintaining the structural integrity of the inner limiting membrane
      (ILM) in the developing retina. In the absence of functional dystroglycan, ILM
      degeneration leads to defective migration, axon guidance, and mosaic spacing of
      neurons and a loss of multiple neuron types during retinal development. These
      results demonstrate that disorganization of retinal circuit development is a
      likely contributor to visual dysfunction in patients with dystroglycanopathy.

PMID- 28760866
TI  - Learning Predictive Statistics: Strategies and Brain Mechanisms.
AB  - When immersed in a new environment, we are challenged to decipher initially
      incomprehensible streams of sensory information. However, quite rapidly, the
      brain finds structure and meaning in these incoming signals, helping us to
      predict and prepare ourselves for future actions. This skill relies on extracting
      the statistics of event streams in the environment that contain regularities of
      variable complexity from simple repetitive patterns to complex probabilistic
      combinations. Here, we test the brain mechanisms that mediate our ability to
      adapt to the environment's statistics and predict upcoming events. By combining
      behavioral training and multisession fMRI in human participants (male and
      female), we track the corticostriatal mechanisms that mediate learning of
      temporal sequences as they change in structure complexity. We show that learning
      of predictive structures relates to individual decision strategy; that is,
      selecting the most probable outcome in a given context (maximizing) versus
      matching the exact sequence statistics. These strategies engage distinct human
      brain regions: maximizing engages dorsolateral prefrontal, cingulate, sensory
      motor regions, and basal ganglia (dorsal caudate, putamen), whereas matching
      engages occipitotemporal regions (including the hippocampus) and basal ganglia
      (ventral caudate). Our findings provide evidence for distinct corticostriatal
      mechanisms that facilitate our ability to extract behaviorally relevant
      statistics to make predictions.SIGNIFICANCE STATEMENT Making predictions about
      future events relies on interpreting streams of information that may initially
      appear incomprehensible. Past work has studied how humans identify repetitive
      patterns and associative pairings. However, the natural environment contains
      regularities that vary in complexity from simple repetition to complex
      probabilistic combinations. Here, we combine behavior and multisession fMRI to
      track the brain mechanisms that mediate our ability to adapt to changes in the
      environment's statistics. We provide evidence for an alternate route for learning
      complex temporal statistics: extracting the most probable outcome in a given
      context is implemented by interactions between executive and motor
      corticostriatal mechanisms compared with visual corticostriatal circuits
      (including hippocampal cortex) that support learning of the exact temporal
      statistics.

PMID- 28760867
TI  - Asymmetric Dichoptic Masking in Visual Cortex of Amblyopic Macaque Monkeys.
AB  - In amblyopia, abnormal visual experience leads to an extreme form of eye
      dominance, in which vision through the nondominant eye is degraded. A key aspect
      of this disorder is perceptual suppression: the image seen by the stronger eye
      often dominates during binocular viewing, blocking the image of the weaker eye
      from reaching awareness. Interocular suppression is the focus of ongoing work
      aimed at understanding and treating amblyopia, yet its physiological basis
      remains unknown. We measured binocular interactions in visual cortex of
      anesthetized amblyopic monkeys (female Macaca nemestrina), using 96-channel
      "Utah" arrays to record from populations of neurons in V1 and V2. In an
      experiment reported recently (Hallum et al., 2017), we found that reduced
      excitatory input from the amblyopic eye (AE) revealed a form of balanced
      binocular suppression that is unaltered in amblyopia. Here, we report on the
      modulation of the gain of excitatory signals from the AE by signals from its
      dominant fellow eye (FE). Using a dichoptic masking technique, we found that AE
      responses to grating stimuli were attenuated by the presentation of a noise mask
      to the FE, as in a normal control animal. Responses to FE stimuli, by contrast,
      could not be masked from the AE. We conclude that a weakened ability of the
      amblyopic eye to modulate cortical response gain creates an imbalance of
      suppression that favors the dominant eye.SIGNIFICANCE STATEMENT In amblyopia,
      vision in one eye is impaired as a result of abnormal early visual experience.
      Behavioral observations in humans with amblyopia suggest that much of their
      visual loss is due to active suppression of their amblyopic eye. Here we describe
      experiments in which we studied binocular interactions in macaques with
      experimentally induced amblyopia. In normal monkeys, the gain of neuronal
      response to stimulation of one eye is modulated by contrast in the other eye, but
      in monkeys with amblyopia the balance of gain modulation is altered so that the
      weaker, amblyopic eye has little effect while the stronger fellow eye has a
      strong effect. This asymmetric suppression may be a key component of the
      perceptual losses in amblyopia.

PMID- 28760868
TI  - Polysialylation at Early Stages of Oligodendrocyte Differentiation Promotes
      Myelin Repair.
AB  - Polysialic acid is a glycan modification of the neural cell adhesion molecule
      (NCAM) produced by the polysialyltransferases ST8SIA2 and ST8SIA4. Polysialic
      acid has been detected in multiple sclerosis plaques, but its beneficial or
      adverse role in remyelination is elusive. Here, we show that, despite a
      developmental delay, myelination at the onset and during cuprizone-induced
      demyelination was unaffected in male Ncam1-/- or St8sia2-/- mice. However,
      remyelination, restoration of oligodendrocyte densities, and motor recovery after
      the cessation of cuprizone treatment were compromised. Impaired differentiation
      of NCAM- or ST8SIA2-negative oligodendrocyte precursors suggested an underlying
      cell-autonomous mechanism. In contrast, premature differentiation in ST8SIA4
      negative cultures explained the accelerated remyelination previously observed in
      St8sia4-/- mice. mRNA profiling during differentiation of human stem cell-derived
      and primary murine oligodendrocytes indicated that the opposing roles of ST8SIA2
      and ST8SIA4 arise from sequential expression. We also provide evidence that
      potentiation of ST8SIA2 by 9-cis-retinoic acid and artificial polysialylation of
      oligodendrocyte precursors by a bacterial polysialyltransferase are mechanisms to
      promote oligodendrocytic differentiation. Thus, differential targeting of
      polysialyltransferases and polysialic acid engineering are promising strategies
      to advance the treatment of demyelinating diseases.SIGNIFICANCE STATEMENT The
      beneficial or adverse role of polysialic acid (polySia) in myelin repair is a
      long-standing question. As a modification of the neural cell adhesion molecule
      (NCAM), polySia is produced by the polysialyltransferases ST8SIA2 and ST8SIA4.
      Here we demonstrate that NCAM and ST8SIA2 promote oligodendrocyte differentiation
      and myelin repair as well as motor recovery after cuprizone-induced
      demyelination. In contrast, ST8SIA4 delays oligodendrocyte differentiation,
      explaining its adverse role in remyelination. These opposing roles of the
      polysialyltransferases are based on different expression profiles. 9-cis-retinoic
      acid enhances ST8SIA2 expression, providing a mechanism for understanding how it
      supports oligodendrocyte differentiation and remyelination. Furthermore,
      artificial polysialylation of the cell surface promotes oligodendrocyte
      differentiation. Thus, boosting ST8SIA2 and engineering of polySia are promising
      strategies for improving myelin repair.

PMID- 28760870
TI  - Intensive Blood Pressure Lowering and Regression of Left Ventricular Hypertrophy.

PMID- 28760869
TI  - Stable Coronary Syndromes: The Case for Consolidating the Nomenclature of Stable
      Ischemic Heart Disease.

PMID- 28760872
TI  - Soda Taxes Take Off Across the Country.

PMID- 28760871
TI  - Should We Perform Catheter Ablation for Asymptomatic Atrial Fibrillation?
AB  - Since the original description of atrial fibrillation ablation, numerous studies
      have demonstrated the superiority of catheter ablation over pharmacological
      therapy for maintenance of sinus rhythm in patients with both paroxysmal and
      persistent atrial fibrillation. However, to date, no randomized studies have been
      powered to demonstrate a mortality or stroke reduction benefit of rhythm control
      with catheter ablation over a rate control strategy. The results of such ongoing
      studies are not expected until 2018 or 2019. Thus, the only indication for atrial
      fibrillation ablation in recent guidelines has been the presence of symptoms.
      However, up to 40% of an atrial fibrillation population may be asymptomatic. In
      2017, in the absence of randomized studies, are there nevertheless data that
      support atrial fibrillation ablation in asymptomatic patients?

PMID- 28760873
TI  - Chest Pain in an 18-Year-Old Man.

PMID- 28760874
TI  - Letter by Shi et al Regarding Article, "Body Mass Index and Mortality Among
      Adults Undergoing Cardiac Surgery: A Nationwide Study With a Systematic Review
      and Meta-Analysis".

PMID- 28760875
TI  - Letter by Banack et al Regarding Article, "Body Mass Index and Mortality Among
      Adults Undergoing Cardiac Surgery: A Nationwide Study With a Systematic Review
      and Meta-Analysis".

PMID- 28760876
TI  - Letter by Butcher et al Regarding Article, "Body Mass Index and Mortality Among
      Adults Undergoing Cardiac Surgery: A Nationwide Study With a Systematic Review
      and Meta-Analysis".

PMID- 28760877
TI  - Response by Mariscalco and Murphy to Letters Regarding Article, "Body Mass Index
      and Mortality Among Adults Undergoing Cardiac Surgery: A Nationwide Study With a
      Systematic Review and Meta-Analysis".

PMID- 28760878
TI  - Correction to: Effect of Intensive Blood Pressure Lowering on Left Ventricular
      Hypertrophy in Patients With Hypertension: SPRINT (Systolic Blood Pressure
      Intervention Trial).

PMID- 28760879
TI  - PACT Facilitates RNA-Induced Activation of MDA5 by Promoting MDA5
      Oligomerization.
AB  - MDA5 is a RIG-I-like cytoplasmic sensor of dsRNA and certain RNA viruses, such as
      encephalomyocarditis virus, for the initiation of the IFN signaling cascade in
      the innate antiviral response. The affinity of MDA5 toward dsRNA is low, and its
      activity becomes optimal in the presence of unknown cellular coactivators. In
      this article, we report an essential coactivator function of dsRNA-binding
      protein PACT in mediating the MDA5-dependent type I IFN response. Virus-induced
      and polyinosinic-polycytidylic acid-induced activation of MDA5 were severely
      impaired in PACT-knockout cells and attenuated in PACT-knockdown cells, but they
      were potentiated when PACT was overexpressed. PACT augmented IRF3-dependent type
      I IFN production subsequent to dsRNA-induced activation of MDA5. In contrast,
      PACT had no influence on MDA5-mediated activation of NF-kappaB. PACT required
      dsRNA interaction for its action on MDA5 and promoted dsRNA-induced
      oligomerization of MDA5. PACT had little stimulatory effect on MDA5 mutants
      deficient for oligomerization and filament assembly. PACT colocalized with MDA5
      in the cytoplasm and potentiated MDA5 recruitment to the dsRNA ligand. Taken
      together, these findings suggest that PACT functions as an essential cellular
      coactivator of RIG-I, as well as MDA5, and it facilitates RNA-induced formation
      of MDA5 oligomers.

PMID- 28760880
TI  - Estrogen Signaling Contributes to Sex Differences in Macrophage Polarization
      during Asthma.
AB  - Allergic asthma is a chronic Th2 inflammation in the lungs that constricts the
      airways and presents as coughing and wheezing. Asthma mostly affects boys in
      childhood and women in adulthood, suggesting that shifts in sex hormones alter
      the course of the disease. Alveolar macrophages have emerged as major mediators
      of allergic lung inflammation in animal models as well as humans. Whether sex
      differences exist in macrophage polarization and the molecular mechanism(s) that
      drive differential responses are not well understood. We found that IL-4
      stimulated bone marrow-derived and alveolar macrophages from female mice
      exhibited greater expression of M2 genes in vitro and after allergen challenge in
      vivo. Alveolar macrophages from female mice exhibited greater expression of the
      IL-4Ralpha and estrogen receptor (ER) alpha compared with macrophages from male
      mice following allergen challenge. An ERalpha-specific agonist enhanced IL-4
      induced M2 gene expression in macrophages from both sexes, but more so in
      macrophages from female mice. Furthermore, IL-4-stimulated macrophages from
      female mice exhibited more transcriptionally active histone modifications at M2
      gene promoters than did macrophages from male mice. We found that supplementation
      of estrogen into ovariectomized female mice enhanced M2 polarization in vivo upon
      challenge with allergen and that macrophage-specific deletion of ERalpha impaired
      this M2 polarization. The effects of estrogen are long-lasting; bone marrow
      derived macrophages from ovariectomized mice implanted with estrogen exhibited
      enhanced IL-4-induced M2 gene expression compared with macrophages from placebo
      implanted littermates. Taken together, our findings suggest that estrogen
      enhances IL-4-induced M2 gene expression and thereby contributes to sex
      differences observed in asthma.

PMID- 28760881
TI  - Evidence for Ig Light Chain Isotype Exclusion in Shark B Lymphocytes Suggests
      Ordered Mechanisms.
AB  - Unlike most vertebrates, the shark IgL gene organization precludes secondary
      rearrangements that delete self-reactive VJ rearranged genes. Nurse sharks
      express four L chain isotypes, kappa, lambda, sigma, and sigma-2, encoded by 35
      functional minigenes or clusters. The sequence of gene activation/expression and
      receptor editing of these isotypes have not been studied. We therefore
      investigated the extent of isotypic exclusion in separated B cell subpopulations.
      Surface Ig (sIg)kappa-expressing cells, isolated with mAb LK14 that recognizes
      Ckappa, carry predominantly nonproductive rearrangements of other L chain
      isotypes. Conversely, after depletion with LK14, sIgM+ cells contained largely
      nonproductive kappa and enrichment for in-frame VJ of the others. Because some
      isotypic inclusion was observed at the mRNA level, expression in the BCR was
      examined. Functional lambda mRNA was obtained, as expected, from the LK14
      depleted population, but was also in sIgkappa+ splenocytes. Whereas lambda
      somatic mutants from the depleted sample displayed evidence of positive
      selection, the lambda genes in sIgkappa+ cells accumulated bystander mutations
      indicating a failure to express their products at the cell surface in association
      with the BCR H chain. In conclusion, a shark B cell expresses one L chain isotype
      at the surface and other isotypes as nonproductive VJ, sterile transcripts, or in
      frame VJ whose products may not associate with the H chain. Based on the mRNA
      content found in the B cell subpopulations, an order of L chain gene activation
      is suggested as: sigma-2 followed by kappa, then sigma and lambda.

PMID- 28760882
TI  - Modified Vaccinia Virus Ankara Vector Induces Specific Cellular and Humoral
      Responses in the Female Reproductive Tract, the Main HIV Portal of Entry.
AB  - The female reproductive tract (FRT) is one of the major mucosal invasion sites
      for HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune
      responses in the FRT after systemic vaccination remain to be characterized. Using
      a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized
      specific immune responses in all compartments of the FRT of nonhuman primates
      after systemic vaccination. Memory T cells were preferentially found in the lower
      tract (vagina and cervix), whereas APCs and innate lymphoid cells were mainly
      located in the upper tract (uterus and fallopian tubes). This
      compartmentalization of immune cells in the FRT was supported by transcriptomic
      analyses and a correlation network. Polyfunctional MVA-specific CD8+ T cells were
      detected in the blood, lymph nodes, vagina, cervix, uterus, and fallopian tubes.
      Anti-MVA IgG and IgA were detected in cervicovaginal fluid after a second vaccine
      dose. Thus, systemic vaccination with an MVA vector elicits cellular and Ab
      responses in the FRT.

PMID- 28760883
TI  - Cutting Edge: NKG2D Signaling Enhances NK Cell Responses but Alone Is
      Insufficient To Drive Expansion during Mouse Cytomegalovirus Infection.
AB  - NK cells play a critical role in host defense against viruses. In this study, we
      investigated the role of NKG2D in the expansion of NK cells after mouse CMV
      (MCMV) infection. Wild-type and NKG2D-deficient (Klrk1-/- ) Ly49H+ NK cells
      proliferated robustly when infected with MCMV strains engineered to allow
      expression of NKG2D ligands, which enhanced the response of wild-type NK cells.
      Naive NK cells exclusively express NKG2D-L, which pairs only with DAP10, whereas
      NKG2D-S expressed by activated NK cells pairs with DAP10 and DAP12, similar to
      Ly49H. However, NKG2D alone was unable to drive robust expansion of Ly49H- NK
      cells when mice were infected with these MCMV strains, likely because NKG2D-S was
      only transiently expressed postinfection. These findings demonstrate that NKG2D
      augments Ly49H-dependent proliferation of NK cells; however, NKG2D signaling
      alone is inadequate for expansion of NK cells, likely due to only transient
      expression of the NKG2D-DAP12 complex.

PMID- 28760884
TI  - HIV-1 Infection Is Associated with Depletion and Functional Impairment of
      Mycobacterium tuberculosis-Specific CD4 T Cells in Individuals with Latent
      Tuberculosis Infection.
AB  - Coinfection with HIV is the single greatest risk factor for reactivation of
      latent Mycobacterium tuberculosis infection (LTBI) and progression to active
      tuberculosis disease. HIV-associated dysregulation of adaptive immunity by
      depletion of CD4 Th cells most likely contributes to loss of immune control of
      LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV
      infection impedes successful T cell-mediated control of M. tuberculosis have not
      been well defined. To further delineate mechanisms whereby HIV impairs protective
      immunity to M. tuberculosis, we evaluated the frequency, phenotype, and
      functional capacity of M. tuberculosis-specific CD4 T cells in HIV-infected and
      HIV-uninfected adults with LTBI. HIV infection was associated with a lower total
      frequency of cytokine-producing M. tuberculosis-specific CD4 T cells, and
      preferential depletion of a discrete subset of M. tuberculosis-specific IFN
      gamma+IL-2-TNF-alpha+ CD4 T cells. M. tuberculosis-specific CD4 T cells in HIV
      infected individuals expressed significantly higher levels of Ki67, compared with
      HIV-uninfected individuals, thus indicating recent activation and turnover of
      these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis
      specific CD4 T cells was markedly impaired in HIV-infected individuals, compared
      with HIV-uninfected individuals. Moreover, HIV infection was associated with
      increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a
      possible mechanism contributing to impaired proliferative capacity of M.
      tuberculosis-specific CD4 T cells in HIV-infected individuals. These data provide
      new insights into the parameters of M. tuberculosis-specific CD4 T cell immunity
      that are impaired in HIV-infected individuals with LTBI, which may contribute to
      their increased risk of developing active tuberculosis disease.

PMID- 28760886
TI  - Intrinsic disorder in the partitioning protein KorB persists after co-operative
      complex formation with operator DNA and KorA.
AB  - The ParB protein, KorB, from the RK2 plasmid is required for DNA partitioning and
      transcriptional repression. It acts co-operatively with other proteins, including
      the repressor KorA. Like many multifunctional proteins, KorB contains regions of
      intrinsically disordered structure, existing in a large ensemble of
      interconverting conformations. Using NMR spectroscopy, circular dichroism and
      small-angle neutron scattering, we studied KorB selectively within its binary
      complexes with KorA and DNA, and within the ternary KorA/KorB/DNA complex. The
      bound KorB protein remains disordered with a mobile C-terminal domain and no
      changes in the secondary structure, but increases in the radius of gyration on
      complex formation. Comparison of wild-type KorB with an N-terminal deletion
      mutant allows a model of the ensemble average distances between the domains when
      bound to DNA. We propose that the positive co-operativity between KorB, KorA and
      DNA results from conformational restriction of KorB on binding each partner,
      while maintaining disorder.

PMID- 28760887
TI  - Structural evidence of a phosphoinositide-binding site in the Rgd1-RhoGAP domain.
AB  - Phosphoinositide lipids recruit proteins to the plasma membrane involved in the
      regulation of cytoskeleton organization and in signalling pathways that control
      cell polarity and growth. Among those, Rgd1p is a yeast GTPase-activating protein
      (GAP) specific for Rho3p and Rho4p GTPases, which control actin polymerization
      and stress signalling pathways. Phosphoinositides not only bind Rgd1p, but also
      stimulate its GAP activity on the membrane-anchored form of Rho4p. Both F-BAR (F
      BAR FCH, and BAR) and RhoGAP domains of Rgd1p are involved in lipid interactions.
      In the Rgd1p-F-BAR domain, a phosphoinositide-binding site has been recently
      characterized. We report here the X-ray structure of the Rgd1p-RhoGAP domain,
      identify by NMR spectroscopy and confirm by docking simulations, a new but
      cryptic phosphoinositide-binding site, comprising contiguous A1, A1' and B
      helices. The addition of helix A1', unusual among RhoGAP domains, seems to be
      crucial for lipid interactions. Such a site was totally unexpected inside a
      RhoGAP domain, as it was not predicted from either the protein sequence or its
      three-dimensional structure. Phosphoinositide-binding sites in RhoGAP domains
      have been reported to correspond to polybasic regions, which are located at the
      unstructured flexible termini of proteins. Solid-state NMR spectroscopy
      experiments confirm the membrane interaction of the Rgd1p-RhoGAP domain upon the
      addition of PtdIns(4,5)P2 and indicate a slight membrane destabilization in the
      presence of the two partners.

PMID- 28760885
TI  - The Neonatal Fc Receptor and Complement Fixation Facilitate Prophylactic Vaccine
      Mediated Humoral Protection against Viral Infection in the Ocular Mucosa.
AB  - The capacity of licensed vaccines to protect the ocular surface against infection
      is limited. Common ocular pathogens, such as HSV-1, are increasingly recognized
      as major contributors to visual morbidity worldwide. Humoral immunity is an
      essential correlate of protection against HSV-1 pathogenesis and ocular
      pathology, yet the ability of Ab to protect against HSV-1 is deemed limited due
      to the slow IgG diffusion rate in the healthy cornea. We show that a live
      attenuated HSV-1 vaccine elicits humoral immune responses that are unparalleled
      by a glycoprotein subunit vaccine vis-a-vis Ab persistence and host protection.
      The live-attenuated vaccine was used to assess the impact of the immunization
      route on vaccine efficacy. The hierarchical rankings of primary immunization
      route with respect to efficacy were s.c. >= mucosal > i.m. Prime-boost
      vaccination via sequential s.c. and i.m. administration yielded greater efficacy
      than any other primary immunization route alone. Moreover, our data support a
      role for complement in prophylactic protection, as evidenced by intracellular
      deposition of C3d in the corneal epithelium of vaccinated animals following
      challenge and delayed viral clearance in C3-deficient mice. We also identify that
      the neonatal Fc receptor (FcRn) is upregulated in the cornea following infection
      or injury concomitant with increased Ab perfusion. Lastly, selective small
      interfering RNA-mediated knockdown of FcRn in the cornea impeded protection
      against ocular HSV-1 challenge in vaccinated mice. Collectively, these findings
      establish a novel mechanism of humoral protection in the eye involving FcRn and
      may facilitate vaccine and therapeutic development for other ocular surface
      diseases.

PMID- 28760888
TI  - AG-348 enhances pyruvate kinase activity in red blood cells from patients with
      pyruvate kinase deficiency.
AB  - Pyruvate kinase (PK) deficiency is a rare genetic disease that causes chronic
      hemolytic anemia. There are currently no targeted therapies for PK deficiency.
      Here, we describe the identification and characterization of AG-348, an
      allosteric activator of PK that is currently in clinical trials for the treatment
      of PK deficiency. We demonstrate that AG-348 can increase the activity of wild
      type and mutant PK enzymes in biochemical assays and in patient red blood cells
      treated ex vivo. These data illustrate the potential for AG-348 to restore the
      glycolytic pathway activity in patients with PK deficiency and ultimately lead to
      clinical benefit.

PMID- 28760889
TI  - Circulating and skin-derived Sezary cells: clonal but with phenotypic plasticity.

PMID- 28760891
TI  - Influence of beta-Lactam Infusion Strategy on Acute Kidney Injury.
AB  - Limited literature is available assessing nephrotoxicity with prolonged beta
      lactam infusions. This study compared the incidence of acute kidney injury (AKI)
      associated with a prolonged beta-lactam infusion or an intermittent infusion.
      This was a retrospective, matched-cohort study at an academic medical center from
      July 2006 to September 2015. Adult patients who received piperacillin-tazobactam
      (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated.
      Patients were excluded for preexisting renal dysfunction or pregnancy. The
      primary outcome was difference in incidence of AKI evaluated using the RIFLE
      (risk, injury, failure, loss, and end-stage) criteria. Patients in the
      intermittent group were matched 3:1 to patients in the prolonged-infusion group
      based on the following: beta-lactam agent, age, gender, Charlson comorbidity
      index, baseline creatinine clearance, hypotension, receipt of vancomycin, and
      treatment in an intensive care unit. A total of 2,390 patients were included in
      the matched analysis, with 1,700 receiving intermittent infusions and 690
      receiving prolonged infusion. The incidence of AKI was similar in the prolonged
      infusion group to that in the intermittent-infusion group (21.6% versus 18.6%; P
      = 0.1). After multivariate regression, prolonged infusion was not associated with
      increased odds of AKI (odds ratio [OR], 1.07; 95% confidence interval [95% CI],
      0.83 to 1.39). Independent predictors of AKI included TZP therapy, concomitant
      nephrotoxins, hypotension, and heart failure. Although AKIs were numerically more
      common in patients receiving prolonged beta-lactam infusions than those receiving
      intermittent infusions, prolonged infusion was not an independent risk factor for
      AKI.

PMID- 28760892
TI  - In Vitro Isolation and Characterization of Oxazolidinone-Resistant Mycobacterium
      tuberculosis.
AB  - Oxazolidinones are promising candidates for the treatment of Mycobacterium
      tuberculosis infections. We isolated linezolid-resistant strains from H37Rv (Euro
      American) and HN878 (East-Asian) strains; resistance frequencies were similar in
      the two strains. Mutations were identified in ribosomal protein L3 (RplC) and the
      23S rRNA (rrl). All mutant strains were cross resistant to sutezolid; a subset
      was cross resistant to chloramphenicol. Mutations in rrl led to growth impairment
      and decreased fitness that may limit spread in clinical settings.

PMID- 28760893
TI  - Fluconazole Pharmacokinetics in Galleria mellonella Larvae and Performance
      Evaluation of a Bioassay Compared to Liquid Chromatography-Tandem Mass
      Spectrometry for Hemolymph Specimens.
AB  - The invertebrate model organism Galleria mellonella can be used to assess the
      efficacy of treatment of fungal infection. The fluconazole dose best mimicking
      human exposure during licensed dosing is unknown. We validated a bioassay for
      fluconazole detection in hemolymph and determined the fluconazole
      pharmacokinetics and pharmacodynamics in larval hemolymph in order to estimate a
      humanized dose for future experiments. A bioassay using 4-mm agar wells, 20 MUl
      hemolymph, and the hypersusceptible Candida albicans DSY2621 was established and
      compared to a validated liquid chromatography-tandem mass spectrometry (LC-MS-MS)
      method. G. mellonella larvae were injected with fluconazole (5, 10, and 20 mg/kg
      of larval weight), and hemolymph was harvested for 24 h for pharmacokinetics
      calculations. The exposure was compared to the human exposure during standard
      licensed dosing. The bioassay had a linear standard curve between 1 and 20
      mg/liter. Accuracy and coefficients of variation (percent) values were below 10%.
      The Spearman coefficient between assays was 0.94. Fluconazole larval
      pharmacokinetics followed one-compartment linear kinetics, with the 24-h area
      under the hemolymph concentration-time curve (AUC24 h) being 93, 173, and 406 mg
      . h/liter for the three doses compared to 400 mg . h/liter in humans under
      licensed treatment. In conclusion, a bioassay was validated for fluconazole
      determination in hemolymph. The pharmacokinetics was linear. An exposure
      comparable to the human exposure during standard licensed dosing was obtained
      with 20 mg/kg.

PMID- 28760894
TI  - First Detailed Genetic Characterization of the Structural Organization of Type
      III Arginine Catabolic Mobile Elements Harbored by Staphylococcus epidermidis by
      Using Whole-Genome Sequencing.
AB  - The type III arginine catabolic mobile element (ACME) was detected in three
      Staphylococcus epidermidis oral isolates recovered from separate patients (one
      healthy, one healthy with dental implants, and one with periodontal disease)
      based on ACME-arc-operon- and ACME-opp3-operon-directed PCR. These isolates were
      subjected to whole-genome sequencing to characterize the precise structural
      organization of ACME III for the first time, which also revealed that all three
      isolates were the same sequence type, ST329.

PMID- 28760895
TI  - A Prospective Cohort Multicenter Study of Molecular Epidemiology and
      Phylogenomics of Staphylococcus aureus Bacteremia in Nine Latin American
      Countries.
AB  - Staphylococcus aureus is an important pathogen causing a spectrum of diseases
      ranging from mild skin and soft tissue infections to life-threatening conditions.
      Bloodstream infections are particularly important, and the treatment approach is
      complicated by the presence of methicillin-resistant S. aureus (MRSA) isolates.
      The emergence of new genetic lineages of MRSA has occurred in Latin America (LA)
      with the rise and dissemination of the community-associated USA300 Latin American
      variant (USA300-LV). Here, we prospectively characterized bloodstream MRSA
      recovered from selected hospitals in 9 Latin American countries. All isolates
      were typed by pulsed-field gel electrophoresis (PFGE) and subjected to antibiotic
      susceptibility testing. Whole-genome sequencing was performed on 96 MRSA
      representatives. MRSA represented 45% of all (1,185 S. aureus) isolates. The
      majority of MRSA isolates belonged to clonal cluster (CC) 5. In Colombia and
      Ecuador, most isolates (>=72%) belonged to the USA300-LV lineage (CC8).
      Phylogenetic reconstructions indicated that MRSA isolates from participating
      hospitals belonged to three major clades. Clade A grouped isolates with sequence
      type 5 (ST5), ST105, and ST1011 (mostly staphylococcal chromosomal cassette mec
      [SCCmec] I and II). Clade B included ST8, ST88, ST97, and ST72 strains (SCCmec
      IV, subtypes a, b, and c/E), and clade C grouped mostly Argentinian MRSA
      belonging to ST30. In summary, CC5 MRSA was prevalent in bloodstream infections
      in LA with the exception of Colombia and Ecuador, where USA300-LV is now the
      dominant lineage. Clonal replacement appears to be a common phenomenon, and
      continuous surveillance is crucial to identify changes in the molecular
      epidemiology of MRSA.

PMID- 28760896
TI  - Evaluation of Posaconazole Serum Concentrations from Delayed-Release Tablets in
      Patients at High Risk for Fungal Infections.
AB  - The purpose of our study was to determine the frequency of patients who achieved
      a therapeutic drug level after receiving posaconazole (PCZ) delayed-release
      tablets (DRT) for prophylaxis or treatment of invasive fungal infections (IFIs)
      and to examine the effect of demographic traits and treatment characteristics on
      PCZ serum levels. A retrospective single-center study was conducted on high-risk
      inpatients at the University of Washington Medical Center (UWMC) that had
      received PCZ and obtained PCZ serum levels for either treatment or prophylaxis
      between 1 August 2014 and 31 August 2015. High-risk patients were defined as
      those undergoing chemotherapy for a primary hematologic malignancy and those
      undergoing hematopoietic cell transplantation (HCT) or solid organ
      transplantation. Serum trough concentrations of >=700 MUg/liter and >=1,000
      MUg/liter were considered appropriate for prophylaxis and treatment,
      respectively. The most frequent underlying medical condition was a hematological
      malignancy (43/53, 81%). Twenty-six of 53 patients (49%) received PCZ for
      prophylaxis; the rest received PCZ for treatment. A total of 37/53 (70%) patients
      had PCZ serum levels of >=700 MUg/liter regardless of indication, including 22/26
      (85%) that received PCZ for prophylaxis. Of the patients that received PCZ for
      treatment, only 12/27 (44%) had PCZ serum levels of >=1,000 MUg/liter. The odds
      of having therapeutic PCZ serum levels were not statistically different in
      patients with a weight of >=90 kg, a diarrhea grade of >=2, a mucositis grade of
      >=2, or poor dietary intake. However, the odds of having therapeutic PCZ serum
      levels was 5.85 times higher in patients without graft-versus-host disease (GVHD)
      treatment than in those with GVHD treatment. Four patients on prophylaxis (15%)
      developed breakthrough IFIs, one of which had a subtherapeutic level. We
      concluded that the use of PCZ DRT provided adequate concentrations in only 70% of
      our patients and that recommended dosing may lead to insufficient levels in
      patients treated for IFIs. Lower concentrations noted among high-risk patients
      with GVHD suggest a need for prospective studies evaluating therapeutic drug
      monitoring and/or dose adjustments among these patients.

PMID- 28760898
TI  - In Vitro Evaluation of Biofilm Dispersal as a Therapeutic Strategy To Restore
      Antimicrobial Efficacy.
AB  - As a proof-of-concept study, the direct impact of biofilm dispersal on the in
      vitro efficacy of imipenem and tobramycin was evaluated against 3-day-old
      biofilms of Pseudomonas aeruginosa Arabinose induction of biofilm dispersal via
      activation of the phosphodiesterase YhjH in the P. aeruginosa engineered strain
      PAO1/p BAD -yhjH resulted in increased antimicrobial efficacy and synergy of the
      imipenem-tobramycin combination. These results support the use of biofilm
      dispersal to enhance antimicrobial efficacy in the treatment of biofilm
      associated infections, representing a promising therapeutic strategy.

PMID- 28760897
TI  - Tools for the Individualized Therapy of Teicoplanin for Neonates and Children.
AB  - The aim of this study was to develop a population pharmacokinetic (PK) model for
      teicoplanin across childhood age ranges to be used as Bayesian prior information
      in the software constructed for individualized therapy. We developed a
      nonparametric population model fitted to PK data from neonates, infants, and
      older children. We then implemented this model in the BestDose multiple-model
      Bayesian adaptive control algorithm to show its clinical utility. It was used to
      predict the dosages required to achieve optimal teicoplanin predose targets (15
      mg/liter) from day 3 of therapy. We performed individual simulations for an
      infant and a child from the original population, who provided early first dosing
      interval concentration-time data. An allometric model that used weight as a
      measure of size and that also incorporated renal function using the estimated
      glomerular filtration rate (eGFR), or the ratio of postnatal age (PNA) to serum
      creatinine concentration (SCr) for infants <3 months old, best described the
      data. The median population PK parameters were as follows: elimination rate
      constant (Ke) = 0.03 . (wt/70)-0.25 . Renal (h-1); V = 19.5 . (wt/70) (liters);
      Renal = eGFR0.07 (ml/min/1.73 m2), or Renal = PNA/SCr (MUmol/liter). Increased
      teicoplanin dosages and alternative administration techniques (extended infusions
      and fractionated multiple dosing) were required in order to achieve the targets
      safely by day 3 in simulated cases. The software was able to predict individual
      measured concentrations and the dosages and administration techniques required to
      achieve the desired target concentrations early in therapy. Prospective
      evaluation is now needed in order to ensure that this individualized teicoplanin
      therapy approach is applicable in the clinical setting. (This study has been
      registered in the European Union Clinical Trials Register under EudraCT no. 2012
      005738-12.).

PMID- 28760899
TI  - Susceptibility of Mycobacterium tuberculosis Cytochrome bd Oxidase Mutants to
      Compounds Targeting the Terminal Respiratory Oxidase, Cytochrome c.
AB  - We deleted subunits I (cydA) and II (cydB) of the Mycobacterium tuberculosis
      cytochrome bd menaquinol oxidase. The resulting DeltacydA and DeltacydAB mutants
      were hypersusceptible to compounds targeting the mycobacterial bc1 menaquinol
      cytochrome c oxidoreductase and exhibited bioenergetic profiles indistinguishable
      from strains deficient in the ABC-type transporter, CydDC, predicted to be
      essential for cytochrome bd assembly. These results confirm CydAB and CydDC as
      potential targets for drugs aimed at inhibiting a terminal respiratory oxidase
      implicated in pathogenesis.

PMID- 28760900
TI  - Population Pharmacokinetics of High-Dose Continuous-Infusion Meropenem and
      Considerations for Use in the Treatment of Infections Due to KPC-Producing
      Klebsiella pneumoniae.
AB  - We assessed the population pharmacokinetics of high-dose continuous-infusion
      (HDCI) meropenem in a cohort of patients with Klebsiella pneumoniae carbapenemase
      (KPC)-producing Klebsiella pneumoniae (KPC-Kp) infections. Monte Carlo
      simulations were used to define the permissible HDCI meropenem regimens that
      could be safely considered for the treatment of KPC-Kp infections due to
      meropenem-resistant strains. Permissible doses were arbitrarily defined as those
      associated with a <=10% to 15% likelihood of meropenem steady-state
      concentrations (Css) of >100 mg/liter. Probabilities of target attainment (PTA)
      of four incremental pharmacodynamic determinants for meropenem efficacy (100%
      T>1*MIC, 100% T>2*MIC, 100% T>3*MIC, and 100% T>4*MIC, where "T>MIC" represents
      the time during which the plasma concentration of this time-dependent
      antibacterial agent is maintained above the MIC for the pathogen) in relation to
      different classes of renal function were calculated. The cumulative fractions of
      response (CFR) for the permissible HDCI meropenem regimens were calculated
      against the MIC distribution of the KPC-Kp clinical isolates that were collected
      routinely at our University Hospital between 2013 and 2016 (n = 169). Ninety
      seven meropenem Css were included in the analysis. The final model included
      creatinine clearance (CrCL) as a covariate and explained 94% of the population
      variability. Monte Carlo simulations based on licensed dosages of up to 6 g/day
      predicted an acceptable PTA (>80%) of 100% T>1*MIC against KPC-Kp with a
      meropenem MIC of <=32 mg/liter in patients with a CrCL level of <130 ml/min.
      Dosages of 8 g/day were needed for achieving the same target in patients with
      CrCL at levels of 130 to 200 ml/min. In dealing with pathogens with a meropenem
      MIC of 64 mg/liter, HDCI regimens using meropenem at higher than licensed levels
      should be considered. In these cases, real-time therapeutic drug monitoring could
      be a useful adjunct for optimized care. The predicted CFR were >75% in all of the
      classes of renal function.

PMID- 28760901
TI  - Synthetic Porcine Hepcidin Exhibits Different Roles in Escherichia coli and
      Salmonella Infections.
AB  - Hepcidin, an antimicrobial peptide, was discovered to integrate diverse signals
      from iron status and an infection threat and orchestrate a series of host
      protective responses. Several studies have investigated the antimicrobial role of
      hepcidin, but the results have been controversial. Here, we aimed to examine the
      role of hepcidin in bacterial adherence and invasion in vitro We found that
      porcine hepcidin could decrease the amount of the extracellular pathogen
      enterotoxigenic Escherichia coli (ETEC) K88 that adhered to cells because it
      caused the aggregation of the bacteria. However, addition of hepcidin to
      macrophages infected with the intracellular pathogen Salmonella enterica serovar
      Typhimurium enhanced the intracellular growth of the pathogen through the
      degradation of ferroportin, an iron export protein, and then the sequestration of
      intracellular iron. Intracellular iron was unavailable by use of the iron
      chelator deferiprone (DFO), which reduced intracellular bacterial growth. These
      results demonstrate that hepcidin exhibits different functions in extracellular
      and intracellular bacterial infections, which suggests that different defense
      strategies should be taken to prevent bacterial infection.

PMID- 28760902
TI  - Mycobacterium abscessus l,d-Transpeptidases Are Susceptible to Inactivation by
      Carbapenems and Cephalosporins but Not Penicillins.
AB  - As a growing number of clinical isolates of Mycobacterium abscessus are resistant
      to most antibiotics, new treatment options that are effective against these drug
      resistant strains are desperately needed. The majority of the linkages in the
      cell wall peptidoglycan of M. abscessus are synthesized by nonclassical
      transpeptidases, namely, the l,d-transpeptidases. Emerging evidence suggests that
      these enzymes represent a new molecular vulnerability in this pathogen. Recent
      studies have demonstrated that inhibition of these enzymes by the carbapenem
      class of beta-lactams determines their activity against Mycobacterium
      tuberculosis Here, we studied the interactions of beta-lactams with two l,d
      transpeptidases in M. abscessus, namely, LdtMab1 and LdtMab2, and found that both
      the carbapenem and cephalosporin, but not penicillin, subclasses of beta-lactams
      inhibit these enzymes. Contrary to the commonly held belief that combination
      therapy with beta-lactams is redundant, doripenem and cefdinir exhibit synergy
      against both pansusceptible M. abscessus and clinical isolates that are resistant
      to most antibiotics, which suggests that dual-beta-lactam therapy has potential
      for the treatment of M. abscessus Finally, we solved the first crystal structure
      of an M. abscessus l,d-transpeptidase, LdtMab2, and using substitutions of
      critical amino acids in the catalytic site and computational simulations, we
      describe the key molecular interactions between this enzyme and beta-lactams,
      which provide an insight into the molecular basis for the relative efficacy of
      different beta-lactams against M. abscessus.

PMID- 28760904
TI  - Molecular Characterization of Fluoroquinolone-Resistant Moraxella catarrhalis
      Variants Generated In Vitro by Stepwise Selection.
AB  - Moraxella catarrhalis causes respiratory infections. In this study,
      fluoroquinolone-resistant strains were selected in vitro to evaluate the
      mechanism of fluoroquinolone resistance. Strains with reduced fluoroquinolone
      susceptibility were obtained by stepwise selection in levofloxacin, and
      fluoroquinolone targets gyr and par were sequenced. Six novel mutations in GyrA
      (D84Y, T594dup, and A722dup), GyrB (E479K and D439N), and ParE (Q395R) involved
      in M. catarrhalis resistance to fluoroquinolones were revealed.

PMID- 28760903
TI  - Tetrazole-Based trans-Translation Inhibitors Kill Bacillus anthracis Spores To
      Protect Host Cells.
AB  - Bacillus anthracis, the causative agent of anthrax, remains a significant threat
      to humans, including potential use in bioterrorism and biowarfare. The capacity
      to engineer strains with increased pathogenicity coupled with the ease of
      disseminating lethal doses of B. anthracis spores makes it necessary to identify
      chemical agents that target and kill spores. Here, we demonstrate that a
      tetrazole-based trans-translation inhibitor, KKL-55, is bactericidal against
      vegetative cells of B. anthracis in culture. Using a fluorescent analog, we show
      that this class of compounds colocalizes with developing endospores and bind
      purified spores in vitro KKL-55 was effective against spores at concentrations
      close to its MIC for vegetative cells. Spore germination was inhibited at 1.2*
      MIC, and spores were killed at 2* MIC. In contrast, ciprofloxacin killed
      germinants at concentrations close to its MIC but did not prevent germination
      even at 32* MIC. Because toxins are released by germinants, macrophages infected
      by B. anthracis spores are killed early in the germination process. At >=2* MIC,
      KKL-55 protected macrophages from death after infection with B. anthracis spores.
      Ciprofloxacin required concentrations of >=8* MIC to exhibit a similar effect.
      Taken together, these data indicate that KKL-55 and related tetrazoles are good
      lead candidates for therapeutics targeting B. anthracis spores and suggest that
      there is an early requirement for trans-translation in germinating spores.

PMID- 28760905
TI  - A 2-Hydroxyisoquinoline-1,3-Dione Active-Site RNase H Inhibitor Binds in Multiple
      Modes to HIV-1 Reverse Transcriptase.
AB  - The RNase H (RNH) function of HIV-1 reverse transcriptase (RT) plays an essential
      part in the viral life cycle. We report the characterization of YLC2-155, a 2
      hydroxyisoquinoline-1,3-dione (HID)-based active-site RNH inhibitor. YLC2-155
      inhibits both polymerase (50% inhibitory concentration [IC50] = 2.6 MUM) and RNH
      functions (IC50 = 0.65 MUM) of RT but is more effective against RNH. X-ray
      crystallography, nuclear magnetic resonance (NMR) analysis, and molecular
      modeling were used to show that YLC2-155 binds at the RNH-active site in multiple
      conformations.

PMID- 28760906
TI  - Mechanisms of Action of Vitamin D as Supplemental Therapy for Pneumocystis
      Pneumonia.
AB  - The combination of trimethoprim and sulfamethoxazole (TMP-SMX) is the most
      effective regimen for therapy of Pneumocystis pneumonia (PCP). As many patients
      with PCP are allergic or do not respond to it, efforts have been devoted to
      develop alternative therapies for PCP. We have found that the combination of
      vitamin D3 (VitD3) (300 IU/kg/day) and primaquine (PMQ) (5 mg/kg/day) was as
      effective as TMP-SMX for therapy of PCP. In this study, we investigated the
      mechanisms by which vitamin D enhances the efficacy of PMQ. C57BL/6 mice were
      immunosuppressed by CD4+ cell depletion, infected with Pneumocystismurina for 8
      weeks, and then treated for 9 days with the combination of VitD3 and PMQ (VitD3
      PMQ) or with TMP-SMX or PMQ to serve as controls. The results showed that vitamin
      D supplementation increased the number of CD11c+ cells, suppressed the production
      of proinflammatory cytokines (tumor necrosis factor alpha [TNF-alpha], gamma
      interferon [IFN-gamma], and interleukin-6 [IL-6]) and inducible nitric oxide
      synthase (iNOS), and enhanced the expression of genes related to antioxidation
      (glutathione reductase and glutamate-cysteine ligase modifier subunit),
      antimicrobial peptides (cathelicidin), and autophagy (ATG5 and beclin-1). These
      results suggest that the main action of vitamin D is enhancing the ability of the
      host to defend against Pneumocystis infection.

PMID- 28760908
TI  - Impact of the underlying etiology of growth hormone deficiency on serum IGF-I SDS
      levels during GH treatment in children.
AB  - CONTEXT: Regular monitoring of serum IGF-I levels during growth hormone (GH)
      therapy has been recommended, for assessing treatment compliance and safety.
      OBJECTIVE: To investigate serum IGF-I SDS levels during GH treatment in children
      with GH deficiency, and to identify potential determinants of these levels.
      DESIGN, PATIENTS AND METHODS: This observational cohort study included all
      patients (n = 308) with childhood-onset non-acquired or acquired GH deficiency
      (GHD) included in the database of a single academic pediatric care center over a
      period of 10 years for whom at least one serum IGF-I SDS determination during GH
      treatment was available. These determinations had to have been carried out
      centrally, with the same immunoradiometric assay. Serum IGF-I SDS levels were
      determined as a function of sex, age and pubertal stage, according to our
      published normative data. RESULTS: Over a median of 4.0 (2-5.8) years of GH
      treatment per patient, 995 serum IGF-I SDS determinations were recorded. In
      addition to BMI SDS, height SDS and GH dose (P < 0.01), etiological group (P <
      0.01) had a significant effect on serum IGF-I SDS levels, with patients suffering
      from acquired GHD having higher serum IGF-I SDS levels than those with non
      acquired GHD, whereas sex, age, pubertal stage, treatment duration, hormonal
      status (isolated GHD (IGHD) vs multiple pituitary hormone deficiency (MPHD)) and
      initial severity of GHD, had no effect. CONCLUSIONS: These original findings have
      important clinical implications for long-term management and highlight the need
      for careful and appropriate monitoring of serum IGF-I SDS and GH dose,
      particularly in patients with acquired GHD, to prevent the unnecessary impact of
      potential comorbid conditions.

PMID- 28760907
TI  - Caspofungin-Mediated Growth Inhibition and Paradoxical Growth in Aspergillus
      fumigatus Involve Fungicidal Hyphal Tip Lysis Coupled with Regenerative
      Intrahyphal Growth and Dynamic Changes in beta-1,3-Glucan Synthase Localization.
AB  - Caspofungin targets cell wall beta-1,3-glucan synthesis and is the international
      consensus guideline-recommended salvage therapy for invasive aspergillosis.
      Although caspofungin is inhibitory at low concentrations, it exhibits a
      paradoxical effect (reversal of growth inhibition) at high concentrations by an
      undetermined mechanism. Treatment with caspofungin at either the growth
      inhibitory concentration (0.5 MUg/ml) or paradoxical growth-inducing
      concentration (4 MUg/ml) for 24 h caused similar abnormalities, including wider,
      hyperbranched hyphae, increased septation, and repeated hyphal tip lysis,
      followed by regenerative intrahyphal growth. By 48 h, only hyphae at the colony
      periphery treated with the high caspofungin concentration displayed paradoxical
      growth. A similar high concentration of caspofungin also induced the paradoxical
      growth of Aspergillus fumigatus during human A549 alveolar cell invasion.
      Localization of the beta-1,3-glucan synthase complex (Fks1 and Rho1) revealed
      significant differences between cells exposed to the growth-inhibitory and
      paradoxical growth-inducing concentrations of caspofungin. At both
      concentrations, Fks1 initially mislocalized from the hyphal tips to vacuoles.
      However, only continuous exposure to 4 MUg/ml of caspofungin for 48 h led to
      recovery of the normal hyphal morphology with renewed localization of Fks1 to
      hyphal tips. Rho1 remained at the hyphal tip after treatment with both
      caspofungin concentrations but was required for paradoxical growth. Farnesol
      blocked paradoxical growth and relocalized Fks1 and Rho1 to vacuoles. Our results
      highlight the importance of regenerative intrahyphal growth as a rapid adaptation
      to the fungicidal lytic effects of caspofungin on hyphal tips and the dynamic
      localization of Fks1 as part of the mechanism for the caspofungin-mediated
      paradoxical response in A. fumigatus.

PMID- 28760909
TI  - Circulating Tumor DNA Reveals Clinically Actionable Somatic Genome of Metastatic
      Bladder Cancer.
AB  - Purpose: Targeted agents and immunotherapies promise to transform the treatment
      of metastatic bladder cancer, but therapy selection will depend on practical
      tumor molecular stratification. Circulating tumor DNA (ctDNA) is established in
      several solid malignancies as a minimally invasive tool to profile the tumor
      genome in real-time, but is critically underexplored in bladder
      cancer.Experimental Design: We applied a combination of whole-exome sequencing
      and targeted sequencing across 50 bladder cancer driver genes to plasma cell-free
      DNA (cfDNA) from 51 patients with aggressive bladder cancer, including 37 with
      metastatic disease.Results: The majority of patients with metastasis, but only
      14% of patients with localized disease, had ctDNA proportions above 2% of total
      cfDNA (median 16.5%, range 3.9%-72.6%). Twelve percent of estimable samples had
      evidence of genome hypermutation. We reveal an aggressive mutational landscape in
      metastatic bladder cancer with 95% of patients harboring deleterious alterations
      to TP53, RB1, or MDM2, and 70% harboring a mutation or disrupting rearrangement
      affecting chromatin modifiers such as ARID1A Targetable alterations in MAPK/ERK
      or PI3K/AKT/mTOR pathways were robustly detected, including amplification of
      ERBB2 (20% of patients) and activating hotspot mutations in PIK3CA (20%), with
      the latter mutually exclusive to truncating mutations in TSC1 A novel FGFR3 gene
      fusion was identified in consecutive samples from one patient.Conclusions: Our
      study demonstrates that ctDNA provides a practical and cost-effective snapshot of
      driver gene status in metastatic bladder cancer. The identification of a wide
      spectrum of clinically informative somatic alterations nominates ctDNA as a tool
      to dissect disease pathogenesis and guide therapy selection in patients with
      metastatic bladder cancer. Clin Cancer Res; 23(21); 6487-97. (c)2017 AACR.

PMID- 28760911
TI  - Tobacco companies' use of retailer incentives after a ban on point-of-sale
      tobacco displays in Scotland.
AB  - INTRODUCTION: Incentives have been used by tobacco companies for many years to
      encourage retailers to sell and promote their products. However, few studies have
      examined the use of retailer incentives in countries with a ban on the open
      display of tobacco products in stores. METHODS: As part of the
      DISPLAY(Determining the Impact of Smoking Point of Sale Legislation Among Youth)
      study, annual qualitative interviews were conducted with 24 small retailers in
      four Scottish communities. This article focuses on data collected in June to July
      2015 and June to July 2016 after a ban on the open display of tobacco was fully
      implemented in Scotland. RESULTS: Retailers described being offered and
      benefiting from a range of financial and other incentives, typically offered via
      tobacco company representatives ('reps'). Most of the retailers received tobacco
      manufacturer support for converting their storage unit to be compliant with the
      new regulations, and several participated in manufacturer 'loyalty' or 'reward'
      schemes. Incentives were additionally offered for maintaining stock levels and
      availability, positioning brands in specified spaces in the public-facing storage
      units (even though products were covered up), increasing sales, trialling new
      products and participating in specific promotions, such as verbally recommending
      specific brands to customers. CONCLUSIONS: Even in a market where the open
      display of tobacco is prohibited, tobacco companies continue to incentivise
      retailers to sell and promote their brands and have developed new promotional
      strategies. For countries that have implemented tobacco display bans, or are
      considering doing so, one option to combat these practices would be to ban
      promotional communications between manufacturers and retailers.

PMID- 28760910
TI  - Epacadostat Shows Value in Two SCCHN Trials.
AB  - In the ECHO-202/KEYNOTE-037 and ECHO-204 trials reported at the 2017 Annual
      Meeting of the American Society of Clinical Oncology, patients with squamous cell
      carcinoma of the head and neck responded well to the combinations of epacadostat
      plus pembrolizumab and epacadostat plus nivolumab. An IDO1 inhibitor, epacadostat
      also demonstrated promising activity in combination with the PD-1 checkpoint
      inhibitors in other solid tumors, including melanoma, urothelial carcinoma, renal
      cell carcinoma, and non-small cell lung cancer.

PMID- 28760913
TI  - Editors' Note.

PMID- 28760912
TI  - When sleep-related hypermotor epilepsy (SHE) met Charles Darwin and Francis
      Galton.
AB  - Sleep-related hypermotor epilepsy (SHE) is characterized by short-lasting
      seizures patterned by repetitive and stereotyped motor events in the same person.
      In autosomal dominant SHE, genetic factors play a well-known key role. In The
      Expression of Emotions in Man and Animals, Charles Darwin quotes a plausible
      example of SHE illustrated by his cousin Sir Francis Galton: "the gentleman...lay
      fast asleep on his back in bed, raising his right arm slowly in front of his
      face, up to his forehead, and then dropping it with a jerk, so that the wrist
      fell heavily on the bridge of his nose. The trick did not occur every night, but
      occasionally, and was independent of any ascertained cause. Sometimes it was
      repeated incessantly for an hour or more." Similar manifestations during sleep
      occurred also in the patient's son and granddaughter, suggesting an autosomal
      inheritance without sex relationship. Differential diagnosis with REM behavior
      disorder and other parasomnias is discussed. To our knowledge, this could be the
      first description of a stereotyped SHE pattern with genetic transmission.

PMID- 28760914
TI  - Letter re: Evolving use of seizure medications after intracerebral hemorrhage: A
      multicenter study.

PMID- 28760915
TI  - Author response: Evolving use of seizure medications after intracerebral
      hemorrhage: A multicenter study.

PMID- 28760916
TI  - Letter re: Neurologists and the economics of MS treatment: Lighting candles, not
      cursing the darkness.

PMID- 28760917
TI  - Author response: Neurologists and the economics of MS treatment: Lighting
      candles, not cursing the darkness.

PMID- 28760918
TI  - Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of
      phase 1 and phase 2 trials.

PMID- 28760919
TI  - Carotid artery web and ischemic stroke: A case-control study.

PMID- 28760920
TI  - Physical activity, but not body mass index, predicts less disability before and
      after stroke.

PMID- 28760921
TI  - Clinical Reasoning: A 22-year-old man with diplopia.

PMID- 28760922
TI  - Pearls & Oy-sters: Transient neurologic events in a patient with leptomeningeal
      metastases.

PMID- 28760923
TI  - Teaching NeuroImages: Bilateral intracerebral hemorrhage in expanded dengue
      syndrome.

PMID- 28760924
TI  - Teaching Video NeuroImages: Running into a "useless" hand.

PMID- 28760925
TI  - The cholesterol ester cycle regulates signalling complexes and synapse damage
      caused by amyloid-beta.
AB  - Cholesterol is required for the formation and function of some signalling
      platforms. In synaptosomes, amyloid-beta (Abeta) oligomers, the causative agent
      in Alzheimer's disease, bind to cellular prion proteins (PrPC) resulting in
      increased cholesterol concentrations, translocation of cytoplasmic phospholipase
      A2 (cPLA2, also known as PLA2G4A) to lipid rafts, and activation of cPLA2 The
      formation of Abeta-PrPC complexes is controlled by the cholesterol ester cycle.
      In this study, Abeta activated cholesterol ester hydrolases, which released
      cholesterol from stores of cholesterol esters and stabilised Abeta-PrPC
      complexes, resulting in activated cPLA2 Conversely, cholesterol esterification
      reduced cholesterol concentrations causing the dispersal of Abeta-PrPC complexes.
      In cultured neurons, the cholesterol ester cycle regulated Abeta-induced synapse
      damage; cholesterol ester hydrolase inhibitors protected neurons, while
      inhibition of cholesterol esterification significantly increased Abeta-induced
      synapse damage. An understanding of the molecular mechanisms involved in the
      dispersal of signalling complexes is important as failure to deactivate
      signalling pathways can lead to pathology. This study demonstrates that
      esterification of cholesterol is a key factor in the dispersal of Abeta-induced
      signalling platforms involved in the activation of cPLA2 and synapse
      degeneration.

PMID- 28760926
TI  - Distinct roles of NFATc1 and NFATc4 in human primary myoblast differentiation and
      in the maintenance of reserve cells.
AB  - Ca2+ signaling plays a key role during human myoblast differentiation. Among Ca2+
      sensitive pathways, calcineurin is essential for myoblast differentiation and
      muscle regeneration. Nuclear factor of activated T-cell (NFAT) transcription
      factors are the major calcineurin targets. We investigated the expression and the
      role of each NFAT gene during human primary myoblast differentiation. We found
      that three NFAT isoforms are present, NFATc1, NFATc3 and NFATc4. Importantly,
      while their mRNA expression increases during differentiation, NFATc1 is more
      highly expressed in myotubes, whilst NFATc4 is specifically maintained in reserve
      cells. NFATc3 is present in both cell types, although no specific role during
      myoblast differentiation was observed. Knockdown of either NFATc1 or NFATc4
      affects the differentiation process similarly, by decreasing the expression of
      late differentiation markers, but impairs myotube formation differently. Whereas
      NFATc1 knockdown strongly reduced the number and the surface area of myotubes,
      NFATc4 knockdown increased the surface area of myotubes and reduced the pool of
      reserve cells. We conclude that NFAT genes have specific roles in myotube
      formation and in the maintenance of the reserve cell pool during human postnatal
      myogenesis.

PMID- 28760927
TI  - Multiple cis-acting signals, some weak by necessity, collectively direct robust
      transport of oskar mRNA to the oocyte.
AB  - Localization of mRNAs can involve multiple steps, each with its own cis-acting
      localization signals and transport factors. How is the transition between
      different steps orchestrated? We show that the initial step in localization of
      Drosophila oskar mRNA - transport from nurse cells to the oocyte - relies on
      multiple cis-acting signals. Some of these are binding sites for the
      translational control factor Bruno, suggesting that Bruno plays an additional
      role in mRNA transport. Although transport of oskar mRNA is essential and robust,
      the localization activity of individual transport signals is weak. Notably,
      increasing the strength of individual transport signals, or adding a strong
      transport signal, disrupts the later stages of oskar mRNA localization. We
      propose that the oskar transport signals are weak by necessity; their weakness
      facilitates transfer of the oskar mRNA from the oocyte transport machinery to the
      machinery for posterior localization.

PMID- 28760928
TI  - Parkin promotes proteasomal degradation of misregulated BAX.
AB  - The pro-apoptotic BCL-2 protein BAX commits human cells to apoptosis by
      permeabilizing the outer mitochondrial membrane. BAX activation has been
      suggested to require the separation of helix alpha5 from alpha6 - the 'latch'
      from the 'core' domain - among other conformational changes. Here, we show that
      conformational changes in this region impair BAX translocation to the
      mitochondria and retrotranslocation back into the cytosol, and therefore BAX
      inhibition, but not activation. Redirecting misregulated BAX to the mitochondria
      revealed an alternative mechanism of BAX inhibition. The E3 ligase parkin, which
      is known to trigger mitochondria-specific autophagy, ubiquitylates BAX K128 and
      targets the pro-apoptotic BCL-2 protein for proteasomal degradation.
      Retrotranslocation-deficient BAX is completely degraded in a parkin-dependent
      manner. Although only a minor pool of endogenous BAX escapes retrotranslocation
      into the cytosol, parkin-dependent targeting of misregulated BAX on the
      mitochondria provides substantial protection against BAX apoptotic activity.

PMID- 28760929
TI  - Entry, Intracellular Survival, and Multinucleated-Giant-Cell-Forming Activity of
      Burkholderia pseudomallei in Human Primary Phagocytic and Nonphagocytic Cells.
AB  - The human pathogen Burkholderia pseudomallei and the related species Burkholderia
      thailandensis are facultative intracellular bacteria characterized by the ability
      to escape into the cytosol of the host cell and to stimulate the formation of
      multinucleated giant cells (MNGCs). MNGC formation is induced via an unknown
      mechanism by bacterial type VI secretion system 5 (T6SS-5), which is an essential
      virulence factor in both species. Despite the vital role of the intracellular
      life cycle in the pathogenesis of the bacteria, the range of host cell types
      permissive for initiation and completion of the intracellular cycle is poorly
      defined. In the present study, we used several different types of human primary
      cells to evaluate bacterial entry, intracellular survival, and MNGC formation. We
      report the capacity of B. pseudomallei to enter, efficiently replicate in, and
      mediate MNGC formation of vein endothelial and bronchial epithelial cells,
      indicating that the T6SS-5 is important in the host-pathogen interaction in these
      cells. Furthermore, we show that B. pseudomallei invades fibroblasts and
      keratinocytes and survives inside these cells as well as in monocyte-derived
      macrophages and neutrophils for at least 17 h postinfection; however, MNGC
      formation is not induced in these cells. In contrast, infection of mixed
      neutrophils and RAW264.7 macrophages with B. thailandensis stimulated the
      formation of heterotypic MNGCs in a T6SS-5-dependent manner. In summary, the
      ability of the bacteria to enter and survive as well as induce MNGC formation in
      certain host cells may contribute to the pathogenesis observed in B. pseudomallei
      infection.

PMID- 28760931
TI  - Streptococcus pneumoniae Colonization Is Required To Alter the Nasal Microbiota
      in Cigarette Smoke-Exposed Mice.
AB  - Smokers have nasal microbiota dysbiosis, with an increased frequency of
      colonizing bacterial pathogens. It is possible that cigarette smoke increases
      pathogen acquisition by perturbing the microbiota and decreasing colonization
      resistance. However, it is difficult to disentangle microbiota dysbiosis due to
      cigarette smoke exposure from microbiota changes caused by increased pathogen
      acquisition in human smokers. Using an experimental mouse model, we investigated
      the impact of cigarette smoke on the nasal microbiota in the absence and presence
      of nasal pneumococcal colonization. We observed that cigarette smoke exposure
      alone did not alter the nasal microbiota composition. The microbiota composition
      was also unchanged at 12 h following low-dose nasal pneumococcal inoculation,
      suggesting that the ability of the microbiota to resist initial nasal
      pneumococcal acquisition was not impaired in smoke-exposed mice. However, nasal
      microbiota dysbiosis occurred as a consequence of established high-dose nasal
      pneumococcal colonization at day 3 in smoke-exposed mice. Similar to clinical
      reports on human smokers, an enrichment of potentially pathogenic bacterial
      genera such as Fusobacterium, Gemella, and Neisseria was observed. Our findings
      suggest that cigarette smoke exposure predisposes to pneumococcal colonization
      independent of changes to the nasal microbiota and that microbiota dysbiosis
      observed in smokers may occur as a consequence of established pathogen
      colonization.

PMID- 28760930
TI  - Downmodulation of Effector Functions in NK Cells upon Toxoplasma gondii
      Infection.
AB  - The obligate intracellular parasite Toxoplasma gondii can actively infect any
      nucleated cell type, including cells from the immune system. The rapid transfer
      of T. gondii from infected dendritic cells to effector natural killer (NK) cells
      may contribute to the parasite's sequestration and shielding from immune
      recognition shortly after infection. However, subversion of NK cell functions,
      such as cytotoxicity or production of proinflammatory cytokines, such as gamma
      interferon (IFN-gamma), upon parasite infection might also be beneficial to the
      parasite. In the present study, we investigated the effects of T. gondii
      infection on NK cells. In vitro, infected NK cells were found to be poor at
      killing target cells and had reduced levels of IFN-gamma production. This could
      be attributed in part to the inability of infected cells to form conjugates with
      their target cells. However, even upon NK1.1 cross-linking of NK cells, the
      infected NK cells also exhibited poor degranulation and IFN-gamma production.
      Similarly, NK cells infected in vivo were also poor at killing target cells and
      producing IFN-gamma. Increased levels of transforming growth factor beta
      production, as well as increased levels of expression of SHP-1 in the cytosol of
      infected NK cells upon infection, were observed in infected NK cells. However,
      the phosphorylation of STAT4 was not altered in infected NK cells, suggesting
      that transcriptional regulation mediates the reduced IFN-gamma production, which
      was confirmed by quantitative PCR. These data suggest that infection of NK cells
      by T. gondii impairs NK cell recognition of target cells and cytokine release,
      two mechanisms that independently could enhance T. gondii survival.

PMID- 28760932
TI  - Tpl2 Promotes Innate Cell Recruitment and Effector T Cell Differentiation To
      Limit Citrobacter rodentium Burden and Dissemination.
AB  - Tumor progression locus 2 (Tpl2) is a serine-threonine kinase that regulates Th1
      differentiation, secretion of the inflammatory cytokine gamma interferon (IFN
      gamma), and host defense against the intracellular pathogens Toxoplasma gondii,
      Listeria monocytogenes, and Mycobacterium tuberculosis However, relatively little
      is known about the contribution of Tpl2 to Th17 differentiation and immune cell
      function during infection with an extracellular pathogen. The goal of this study
      was to determine whether Tpl2 influences the immune response generated to the
      extracellular bacterium Citrobacter rodentium, which induces a mixed Th1 and Th17
      response. During peak infection with C. rodentium, Tpl2-/- mice experienced
      greater bacterial burdens with evidence of dissemination to the liver and spleen
      but ultimately cleared the bacteria within 3 weeks postinfection, similar to the
      findings for wild-type mice. Tpl2-/- mice also recruited fewer neutrophils and
      monocytes to the colon during peak infection, which correlated with increased
      bacterial burdens. In mixed bone marrow chimeras, Tpl2 was shown to play a T cell
      intrinsic role in promoting both IFN-gamma and interleukin-17A production during
      infection with C. rodentium However, upon CD4 T cell transfer into Rag-/- mice,
      Tpl2-/- CD4 T cells were as protective as wild-type CD4 T cells against the
      dissemination of bacteria and mortality. These data indicate that the enhanced
      bacterial burdens in Tpl2-/- mice are not caused primarily by impairments in CD4
      T cell function but result from defects in innate immune cell recruitment and
      function.

PMID- 28760933
TI  - Genetic Evidence for Erythrocyte Receptor Glycophorin B Expression Levels
      Defining a Dominant Plasmodium falciparum Invasion Pathway into Human
      Erythrocytes.
AB  - Plasmodium falciparum, the parasite that causes the deadliest form of malaria,
      has evolved multiple proteins known as invasion ligands that bind to specific
      erythrocyte receptors to facilitate invasion of human erythrocytes. The EBA
      175/glycophorin A (GPA) and Rh5/basigin ligand-receptor interactions, referred to
      as invasion pathways, have been the subject of intense study. In this study, we
      focused on the less-characterized sialic acid-containing receptors glycophorin B
      (GPB) and glycophorin C (GPC). Through bioinformatic analysis, we identified
      extensive variation in glycophorin B (GYPB) transcript levels in individuals from
      Benin, suggesting selection from malaria pressure. To elucidate the importance of
      the GPB and GPC receptors relative to the well-described EBA-175/GPA invasion
      pathway, we used an ex vivo erythrocyte culture system to decrease expression of
      GPA, GPB, or GPC via lentiviral short hairpin RNA transduction of erythroid
      progenitor cells, with global surface proteomic profiling. We assessed the
      efficiency of parasite invasion into knockdown cells using a panel of wild-type
      P. falciparum laboratory strains and invasion ligand knockout lines, as well as
      P. falciparum Senegalese clinical isolates and a short-term-culture-adapted
      strain. For this, we optimized an invasion assay suitable for use with small
      numbers of erythrocytes. We found that all laboratory strains and the majority of
      field strains tested were dependent on GPB expression level for invasion. The
      collective data suggest that the GPA and GPB receptors are of greater importance
      than the GPC receptor, supporting a hierarchy of erythrocyte receptor usage in P.
      falciparum.

PMID- 28760935
TI  - Overexpression of Candida albicans Secreted Aspartyl Proteinases 2 or 5 is not
      sufficient for exacerbation of immunopathology in a murine model of vaginitis.
AB  - The secreted aspartyl protineases of C. albicans have long been implicated in
      virulence at the mucosal surface, including contribution to colonization and
      immunopathogenesis during vulvovaginal candidiasis. In an effort to disentangle
      hypha-associated virulence factor regulation from morphological transition, the
      purpose of this study was to determine if overexpression of SAP2 or SAP5 in a
      efg1Delta/Delta/cph1Delta/Delta mutant could restore capacity to cause
      immunopathology during murine vaginitis to this avirulent hypofilamentous strain.
      Two similar, yet distinct, genetic approaches were used to construct expression
      vectors to achieve SAP overexpression and both genetic and functional assays
      confirmed elevated SAP activity in transformed strains. Similar to previous
      findings, intravaginal challenge of C57Bl/6 mice with hypha-defective strains
      attained high levels of mucosal colonization but failed to induce robust vaginal
      immunopathology (neutrophil recruitment, IL-1beta secretion, lactate
      dehydrogenase release) as compared to the hypha-competent control. Moreover,
      constitutive expression of SAP2 or SAP5 in two distinct sets of such strains did
      not elicit immunopathological markers above that observed during challenge with
      isogenic empty-vector controls. Therefore, these results suggest that
      physiological contribution of SAPs to vaginal immunopathology require hypha
      formation, other hypha-associated factors, or genetic interaction with EFG1
      and/or CPH1 to cause symptomatic infection. Additionally, the outlined expression
      strategy and strain sets will be useful for decoupling other downstream
      morphogenetic factors from hyphal growth.

PMID- 28760937
TI  - Moving Beyond Office Blood Pressure to Achieve a Personalized and More Precise
      Hypertension Management: Which Way to Go?

PMID- 28760934
TI  - Next-Generation Probiotics Targeting Clostridium difficile through Precursor
      Directed Antimicrobial Biosynthesis.
AB  - Integration of antibiotic and probiotic therapy has the potential to lessen the
      public health burden of antimicrobial-associated diseases. Clostridium difficile
      infection (CDI) represents an important example where the rational design of next
      generation probiotics is being actively pursued to prevent disease recurrence.
      Because intrinsic resistance to clinically relevant antibiotics used to treat CDI
      (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic
      species, we screened several bacteria and identified Lactobacillus reuteri to be
      a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria
      convert glycerol to the broad-spectrum antimicrobial compound reuterin. When
      supplemented with glycerol, strains carrying the pocR gene locus were potent
      reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a
      level on par with the level of growth inhibition by vancomycin. Targeted pocR
      mutations and complementation studies identified reuterin to be the precursor
      induced antimicrobial agent. Pathophysiological relevance was demonstrated when
      the codelivery of L. reuteri with glycerol was effective against C. difficile
      colonization in complex human fecal microbial communities, whereas treatment with
      either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome
      and metabolomics analysis independently confirmed that glycerol precursor
      delivery with L. reuteri elicited changes in the composition and function of the
      human microbial community that preferentially targets C. difficile outgrowth and
      toxicity, a finding consistent with glycerol fermentation and reuterin
      production. Antimicrobial resistance has thus been successfully exploited in the
      natural design of human microbiome evasion of C. difficile, and this method may
      provide a prototypic precursor-directed probiotic approach. Antibiotic resistance
      and substrate bioavailability may therefore represent critical new determinants
      of probiotic efficacy in clinical trials.

PMID- 28760938
TI  - Vasorelaxation to the Nitroxyl Donor Isopropylamine NONOate in Resistance
      Arteries Does Not Require Perivascular Calcitonin Gene-Related Peptide.
AB  - Nitroxyl (HNO) donors offer considerable therapeutic potential for the treatment
      of hypertension-related cardiovascular disorders, particularly heart failure, as
      they combine an inotropic action with peripheral vasodilation. Angeli's salt is
      the only HNO donor whose mechanism has been studied in depth, and recently,
      Angeli's salt vasodilation was suggested to be indirect and caused by calcitonin
      gene-related peptide (CGRP) released from perivascular nerves after HNO activates
      TRPA1 (transient receptor potential cation channel subfamily A member 1)
      channels. We investigated resistance artery vasorelaxation to the HNO donor,
      isopropylamine NONOate (IPA/NO), one of the structures providing a template for
      therapeutic development. Wire myography in combination with measurements of
      smooth muscle membrane potential was used to characterize the effect of IPA/NO in
      mesenteric resistance arteries. Immunohistochemistry was assessed in pressurized
      arteries. IPA/NO concentration dependently hyperpolarized and relaxed arteries
      precontracted with the alpha1-adrenoreceptor agonist, phenylephrine. These
      effects were blocked by the soluble guanylyl cyclase inhibitor, ODQ (1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) but not by the KATP channel inhibitor,
      glibenclamide. Vasorelaxation persisted in the presence of raised [K+]o, used to
      block hyperpolarization, capsaicin to deplete perivascular CGRP, or HC030031 (2
      (1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4 isopropylphenyl)
      acetamide) to block TRPA1 receptors. Without preconstriction, hyperpolarization
      to IPA/NO was suppressed by glibenclamide, capsaicin, or HC030031.
      Hyperpolarization but not vasorelaxation to exogenous CGRP was inhibited with
      glibenclamide. Thus, vascular hyperpolarization is not necessary for
      vasorelaxation to the HNO donor IPA/NO, even though both effects are cGMP
      dependent. The reduced hyperpolarization after depletion of perivascular CGRP or
      block of TRPA1 receptors indicates some release of CGRP, but this does not
      contribute to HNO vasorelaxation. Therefore, HNO-TRPA1-CGRP signaling does not
      seem important for vasodilation to IPA/NO in resistance arteries.

PMID- 28760936
TI  - Caspase-11 Plays a Protective Role in Pulmonary Acinetobacter baumannii
      Infection.
AB  - Activation of caspase-11 by some Gram-negative bacteria triggers the caspase
      1/interleukin 1beta (IL-1beta) pathway, independent of canonical inflammasomes.
      Acinetobacter baumannii is a Gram-negative, conditionally pathogenic bacterium
      that can cause severe pulmonary infection in hospitalized patients. A. baumannii
      was revealed to activate canonical and noncanonical inflammasome pathways in bone
      marrow-derived macrophages (BMDMs). Pulmonary infection of caspase-11-/- mice
      with A. baumannii showed that caspase-11 deficiency impaired A. baumannii
      clearance, exacerbated pulmonary pathological changes, and enhanced
      susceptibility to A. baumannii These data indicate that the caspase-11-mediated
      innate immune response plays a crucial role in defending against A. baumannii.

PMID- 28760939
TI  - Visit-to-Visit Office Blood Pressure Variability and Cardiovascular Outcomes in
      SPRINT (Systolic Blood Pressure Intervention Trial).
AB  - : Studies of visit-to-visit office blood pressure (BP) variability (OBPV) as a
      predictor of cardiovascular events and death in high-risk patients treated to
      lower BP targets are lacking. We conducted a post hoc analysis of SPRINT
      (Systolic Blood Pressure Intervention Trial), a well-characterized cohort of
      participants randomized to intensive (<120 mm Hg) or standard (<140 mm Hg)
      systolic BP targets. We defined OBPV as the coefficient of variation of the
      systolic BP using measurements taken during the 3-,6-, 9-, and 12-month study
      visits. In our cohort of 7879 participants, older age, female sex, black race,
      current smoking, chronic kidney disease, and coronary disease were independent
      determinants of higher OBPV. Use of thiazide-type diuretics or dihydropyridine
      calcium channel blockers was associated with lower OBPV whereas angiotensin
      converting enzyme inhibitors or angiotensin receptor blocker use was associated
      with higher OBPV. There was no difference in OBPV in participants randomized to
      standard or intensive treatment groups. We found that OBPV had no significant
      associations with the composite end point of fatal and nonfatal cardiovascular
      events (n=324 primary end points; adjusted hazard ratio, 1.20; 95% confidence
      interval, 0.85-1.69, highest versus lowest quintile) nor with heart failure or
      stroke. The highest quintile of OBPV (versus lowest) was associated with all
      cause mortality (adjusted hazard ratio, 1.92; confidence interval, 1.22-3.03)
      although the association of OBPV overall with all-cause mortality was marginal
      (P=0.07). Our results suggest that clinicians should continue to focus on office
      BP control rather than on OBPV unless definitive benefits of reducing OBPV are
      shown in prospective trials. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

PMID- 28760941
TI  - Hypertensive Kidney Injury and the Progression of Chronic Kidney Disease.

PMID- 28760940
TI  - Report of the National Heart, Lung, and Blood Institute Working Group on the Role
      of Microbiota in Blood Pressure Regulation: Current Status and Future Directions.

PMID- 28760942
TI  - Perivascular Adipose Tissue Angiotensin II Type 1 Receptor Promotes Vascular
      Inflammation and Aneurysm Formation.
AB  - Perivascular adipose tissue exhibits characteristics of active local
      inflammation, which contributes to the development of atherosclerotic disease as
      a complication of obesity/metabolic syndrome. However, the precise role of
      perivascular adipose tissue in the progression of abdominal aortic aneurysm
      remains unclear. To test the hypothesis that genetic deletion of angiotensin II
      type 1a (AT1a) receptor in perivascular visceral adipose tissue (VAT) can
      attenuate aortic aneurysm formation in apolipoprotein E-deficient (ApoE-/-) mice,
      we performed adipose tissue transplantation experiments by using an angiotensin
      II-induced aneurysm murine model, in which we transplanted VAT from ApoE-/- or
      ApoE-/- AT1a-/- donor mice onto the abdominal aorta of ApoE-/- recipient mice.
      Compared with ApoE-/- VAT transplantation, ApoE-/- AT1a-/- VAT transplantation
      markedly attenuated aortic aneurysm formation, macrophage infiltration, and
      gelatinolytic activity in the abdominal aorta. AT1a receptor activation led to
      the polarization of macrophages in perivascular VAT toward the proinflammatory
      phenotype. Moreover, osteopontin expression and gelatinolytic activity were
      considerably lower in ApoE-/- AT1a-/- perivascular VAT than in ApoE-/-
      perivascular VAT, and angiotensin II-induced osteopontin secretion from
      adipocytes was eliminated after deletion of AT1a receptor in adipocytes. Notably,
      induction of macrophage migration by conditioned medium from angiotensin II
      stimulated wild-type adipocytes was suppressed by treatment with an osteopontin
      neutralizing antibody, and ApoE-/- OPN-/- VAT transplantation more potently
      attenuated aortic aneurysm formation than ApoE-/- VAT transplantation. Our
      findings indicate a previously unrecognized effect of AT1a receptor in
      perivascular VAT on the pathogenesis of abdominal aortic aneurysm.

PMID- 28760943
TI  - Individual and Combined Effects of Dietary Factors on Risk of Incident
      Hypertension: Prospective Analysis From the NutriNet-Sante Cohort.
AB  - Dietary intake is pointed as one of the major determinants in hypertension
      development. Data in the area are mostly obtained from cross-sectional studies.
      We aimed to investigate the prospective association between (1) individual
      nutritional factors and (2) adherence to the Dietary Approach to Stop
      Hypertension and the risk of incident hypertension in a large cohort study. We
      prospectively examined the incidence of hypertension among 80 426 French adults
      participating in the NutriNet-Sante cohort study. Self-reported sociodemographic,
      lifestyle health questionnaires and dietary consumption assessed by three 24-hour
      records were completed at baseline and yearly thereafter. Associations between
      quartiles (Q) of nutrients and food groups and adherence to Dietary Approach to
      Stop Hypertension diet and hypertension risk were assessed by multivariable Cox
      proportional hazards models. During a mean follow-up of 3.4+/-2.1 years, 2413
      cases of incident hypertension were documented. Dietary intakes of sodium (Q4
      versus Q1): hazard ratio (HR)=1.17 (95% confidence interval [CI], 1.02-1.35),
      potassium: HR=0.82 (95% CI, 0.72-0.94), animal protein: HR=1.26 (95% CI, 1.11
      1.43), vegetable protein: HR=0.85 (95% CI, 0.75-0.95), fiber: HR =0.81 (95% CI,
      0.71-0.93), magnesium: HR=0.77 (95% CI, 0.67-0.89), fruit and vegetables: HR=0.85
      (95% CI, 0.74-0.97), whole grain: HR=0.84(95% CI, 0.76-0.93), nuts: HR=0.72 (95%
      CI, 0.63-0.83), and red and processed meat: HR=1.25 (95% CI, 1.11-0.42) were
      associated with risk of hypertension. Besides, adherence to the Dietary Approach
      to Stop Hypertension was strongly inversely associated with incident
      hypertension: (Q4 versus Q1) HR=0.66 (95% CI, 0.58-0.75). Our results confirmed
      the association of several nutritional factors intake and incident hypertension
      and highlighted that adopting a global healthy diet could strongly contribute to
      the prevention of hypertension.

PMID- 28760944
TI  - Vitamin D, Hypertension, and Ischemic Stroke in 116 655 Individuals From the
      General Population: A Genetic Study.
AB  - Observational studies indicate that low concentrations of plasma 25
      hydroxyvitamin D (25(OH)D) are associated with high blood pressure, hypertension,
      and ischemic stroke. However, whether these associations are causal remain
      unknown. A total of 116 655 white individuals of Danish descent from the general
      population were genotyped for genetic variants in DHCR7 and CYP2R1 affecting
      plasma 25(OH)D concentrations; 35 517 had plasma 25(OH)D measurements. Primary
      outcomes were blood pressure, hypertension, and ischemic stroke. Median follow-up
      for incident ischemic stroke was 9.3 years (range, 1 day-33.6 years).
      DHCR7/CYP2R1 allele score was as expected associated with lower 25(OH)D
      concentration (F=328 and R2=1.0%). A genetically determined 10 nmol/L lower
      25(OH)D concentration was associated with a 0.68 (95% confidence interval [CI],
      0.20-1.17) mm Hg higher systolic blood pressure and a 0.36 (95% CI, 0.08-0.63) mm
      Hg higher diastolic blood pressure with corresponding observational estimates of
      0.58 (95% CI, 0.50-0.68) and 0.40 (95% CI, 0.35-0.45) mm Hg. The odds ratio for
      hypertension was 1.02 (95% CI, 0.97-1.08) for a genetically determined 10 nmol/L
      lower 25(OH)D with a corresponding observational odds ratio of 1.06 (95% CI, 1.05
      1.07). The odds ratio for ischemic stroke was 0.98 (95% CI, 0.86-1.13) for a
      genetically determined 10 nmol/L decrease in 25(OH)D with a corresponding
      observational odds ratio of 1.03 (95% CI, 1.01-1.05). Genetic and observational
      low 25(OH)D concentrations were associated with higher blood pressure, as well as
      with hypertension consistent with causal relationships. Because observational but
      not genetic low 25(OH)D concentration was associated with ischemic stroke, and as
      the CIs overlapped, we can neither support nor exclude a causal relationship.

PMID- 28760945
TI  - Inactivation of Nitric Oxide Synthesis Exacerbates the Development of Alzheimer
      Disease Pathology in APPPS1 Mice (Amyloid Precursor Protein/Presenilin-1).
AB  - The epidemiological link between hypertension and Alzheimer disease is
      established. We previously reported that hypertension aggravates the Alzheimer
      like pathology in APPPS1 mice (amyloid precursor protein/presenilin-1, mouse
      model of Alzheimer disease) with angiotensin II-induced hypertension, in relation
      with hypertension and nitric oxide deficiency. To provide further insights into
      the role of nitric oxide in the hypertension-Alzheimer disease cross-talk, we
      studied the effects of nitric oxide blockade in APPPS1 mice using N(omega)-nitro
      l-arginine methyl ester (l-NAME) alone or in combination with hydralazine, to
      normalize blood pressure. Compared with normotensive APPPS1 mice, those with l
      NAME-induced hypertension had greater amyloid burden (P<0.05), increased cortical
      amyloid angiopathy (P<0.01), decreased regional microvascular density (P<0.05),
      and deficient long-term spatial reference memory (P<0.001). Blood pressure
      normalization with hydralazine did not protect APPPS1 mice from l-NAME-induced
      deterioration except for cortical amyloid angiopathy, linked to hypertension
      induced arterial wall remodeling. By testing the cerebrovascular response to
      hypercapnic breathing, we evidenced early functional impairment of cerebral
      vasomotor activity in APPPS1 mice. Whereas in control wild-type normotensive
      mice, carbon dioxide breathing resulted in 15+/-1.3% increase in the mean blood
      flow velocity (P<0.001), paradoxical mild decrease (1.5+/-0.4%) was recorded in
      normotensive APPPS1 mice (P<0.001). Carbon dioxide-induced decrease in mean blood
      flow velocity was not significantly modified in l-NAME-treated hypertensive
      APPPS1 mice (2.5+/-1.2%) and partly reversed to mild vasodilation by hydralazine
      (3.2+/-1.5%, P<0.01). These results suggest that impaired nitric oxide
      bioavailability exacerbates the pathophysiology of Alzheimer disease, essentially
      impacting amyloid load and cognitive impairment, independently of l-NAME-induced
      hypertension. Only cerebral amyloid angiopathy seems to be dependent on
      hypertension.

PMID- 28760946
TI  - Vitamin D, Hypertension, and Ischemic Stroke: An Unresolved Relationship.

PMID- 28760947
TI  - Which app should I use? Patients and doctors are making increasing use of health
      apps, but there is little guidance about how well they work.

PMID- 28760948
TI  - Nitrogen-fixing trees inhibit growth of regenerating Costa Rican rainforests.
AB  - More than half of the world's tropical forests are currently recovering from
      human land use, and this regenerating biomass now represents the largest carbon
      (C)-capturing potential on Earth. How quickly these forests regenerate is now a
      central concern for both conservation and global climate-modeling efforts.
      Symbiotic nitrogen-fixing trees are thought to provide much of the nitrogen (N)
      required to fuel tropical secondary regrowth and therefore to drive the rate of
      forest regeneration, yet we have a poor understanding of how these N fixers
      influence the trees around them. Do they promote forest growth, as expected if
      the new N they fix facilitates neighboring trees? Or do they suppress growth, as
      expected if competitive inhibition of their neighbors is strong? Using 17
      consecutive years of data from tropical rainforest plots in Costa Rica that range
      from 10 y since abandonment to old-growth forest, we assessed how N fixers
      influenced the growth of forest stands and the demographic rates of neighboring
      trees. Surprisingly, we found no evidence that N fixers facilitate biomass
      regeneration in these forests. At the hectare scale, plots with more N-fixing
      trees grew slower. At the individual scale, N fixers inhibited their neighbors
      even more strongly than did nonfixing trees. These results provide strong
      evidence that N-fixing trees do not always serve the facilitative role to
      neighboring trees during tropical forest regeneration that is expected given
      their N inputs into these systems.

PMID- 28760949
TI  - Homeostatic enhancement of sensory transduction.
AB  - Our sense of hearing boasts exquisite sensitivity, precise frequency
      discrimination, and a broad dynamic range. Experiments and modeling imply,
      however, that the auditory system achieves this performance for only a narrow
      range of parameter values. Small changes in these values could compromise hair
      cells' ability to detect stimuli. We propose that, rather than exerting tight
      control over parameters, the auditory system uses a homeostatic mechanism that
      increases the robustness of its operation to variation in parameter values. To
      slowly adjust the response to sinusoidal stimulation, the homeostatic mechanism
      feeds back a rectified version of the hair bundle's displacement to its
      adaptation process. When homeostasis is enforced, the range of parameter values
      for which the sensitivity, tuning sharpness, and dynamic range exceed specified
      thresholds can increase by more than an order of magnitude. Signatures in the
      hair cell's behavior provide a means to determine through experiment whether such
      a mechanism operates in the auditory system. Robustness of function through
      homeostasis may be ensured in any system through mechanisms similar to those that
      we describe here.

PMID- 28760950
TI  - QnAs with Daan Frenkel.

PMID- 28760951
TI  - Cdk5-dependent phosphorylation of liprinalpha1 mediates neuronal activity
      dependent synapse development.
AB  - The experience-dependent modulation of brain circuitry depends on dynamic changes
      in synaptic connections that are guided by neuronal activity. In particular,
      postsynaptic maturation requires changes in dendritic spine morphology, the
      targeting of postsynaptic proteins, and the insertion of synaptic
      neurotransmitter receptors. Thus, it is critical to understand how neuronal
      activity controls postsynaptic maturation. Here we report that the scaffold
      protein liprinalpha1 and its phosphorylation by cyclin-dependent kinase 5 (Cdk5)
      are critical for the maturation of excitatory synapses through regulation of the
      synaptic localization of the major postsynaptic organizer postsynaptic density
      (PSD)-95. Whereas Cdk5 phosphorylates liprinalpha1 at Thr701, this
      phosphorylation decreases in neurons in response to neuronal activity. Blockade
      of liprinalpha1 phosphorylation enhances the structural and functional maturation
      of excitatory synapses. Nanoscale superresolution imaging reveals that inhibition
      of liprinalpha1 phosphorylation increases the colocalization of liprinalpha1 with
      PSD-95. Furthermore, disruption of liprinalpha1 phosphorylation by a small
      interfering peptide, siLIP, promotes the synaptic localization of PSD-95 and
      enhances synaptic strength in vivo. Our findings collectively demonstrate that
      the Cdk5-dependent phosphorylation of liprinalpha1 is important for the
      postsynaptic organization during activity-dependent synapse development.

PMID- 28760954
TI  - Glacial weathering, sulfide oxidation, and global carbon cycle feedbacks.
AB  - Connections between glaciation, chemical weathering, and the global carbon cycle
      could steer the evolution of global climate over geologic time, but even the
      directionality of feedbacks in this system remain to be resolved. Here, we
      assemble a compilation of hydrochemical data from glacierized catchments, use
      this data to evaluate the dominant chemical reactions associated with glacial
      weathering, and explore the implications for long-term geochemical cycles.
      Weathering yields from catchments in our compilation are higher than the global
      average, which results, in part, from higher runoff in glaciated catchments. Our
      analysis supports the theory that glacial weathering is characterized
      predominantly by weathering of trace sulfide and carbonate minerals. To evaluate
      the effects of glacial weathering on atmospheric pCO2, we use a solute mixing
      model to predict the ratio of alkalinity to dissolved inorganic carbon (DIC)
      generated by weathering reactions. Compared with nonglacial weathering, glacial
      weathering is more likely to yield alkalinity/DIC ratios less than 1, suggesting
      that enhanced sulfide oxidation as a result of glaciation may act as a source of
      CO2 to the atmosphere. Back-of-the-envelope calculations indicate that oxidative
      fluxes could change ocean-atmosphere CO2 equilibrium by 25 ppm or more over 10
      ky. Over longer timescales, CO2 release could act as a negative feedback,
      limiting progress of glaciation, dependent on lithology and the concentration of
      atmospheric O2 Future work on glaciation-weathering-carbon cycle feedbacks should
      consider weathering of trace sulfide minerals in addition to silicate minerals.

PMID- 28760953
TI  - CD318 is a ligand for CD6.
AB  - It has been proposed that CD6, an important regulator of T cells, functions by
      interacting with its currently identified ligand, CD166, but studies performed
      during the treatment of autoimmune conditions suggest that the CD6-CD166
      interaction might not account for important functions of CD6 in autoimmune
      diseases. The antigen recognized by mAb 3A11 has been proposed as a new CD6
      ligand distinct from CD166, yet the identity of it is hitherto unknown. We have
      identified this CD6 ligand as CD318, a cell surface protein previously found to
      be present on various epithelial cells and many tumor cells. We found that, like
      CD6 knockout (KO) mice, CD318 KO mice are also protected in experimental
      autoimmune encephalomyelitis. In humans, we found that CD318 is highly expressed
      in synovial tissues and participates in CD6-dependent adhesion of T cells to
      synovial fibroblasts. In addition, soluble CD318 is chemoattractive to T cells
      and levels of soluble CD318 are selectively and significantly elevated in the
      synovial fluid from patients with rheumatoid arthritis and juvenile inflammatory
      arthritis. These results establish CD318 as a ligand of CD6 and a potential
      target for the diagnosis and treatment of autoimmune diseases such as multiple
      sclerosis and inflammatory arthritis.

PMID- 28760952
TI  - Testing inhomogeneous solvation theory in structure-based ligand discovery.
AB  - Binding-site water is often displaced upon ligand recognition, but is commonly
      neglected in structure-based ligand discovery. Inhomogeneous solvation theory
      (IST) has become popular for treating this effect, but it has not been tested in
      controlled experiments at atomic resolution. To do so, we turned to a grid-based
      version of this method, GIST, readily implemented in molecular docking. Whereas
      the term only improves docking modestly in retrospective ligand enrichment, it
      could be added without disrupting performance. We thus turned to prospective
      docking of large libraries to investigate GIST's impact on ligand discovery,
      geometry, and water structure in a model cavity site well-suited to exploring
      these terms. Although top-ranked docked molecules with and without the GIST term
      often overlapped, many ligands were meaningfully prioritized or deprioritized;
      some of these were selected for testing. Experimentally, 13/14 molecules
      prioritized by GIST did bind, whereas none of the molecules that it deprioritized
      were observed to bind. Nine crystal complexes were determined. In six, the ligand
      geometry corresponded to that predicted by GIST, for one of these the pose
      without the GIST term was wrong, and three crystallographic poses differed from
      both predictions. Notably, in one structure, an ordered water molecule with a
      high GIST displacement penalty was observed to stay in place. Inclusion of this
      water-displacement term can substantially improve the hit rates and ligand
      geometries from docking screens, although the magnitude of its effects can be
      small and its impact in drug binding sites merits further controlled studies.

PMID- 28760955
TI  - Light-responsive organic flashing electron ratchet.
AB  - Ratchets are nonequilibrium devices that produce directional motion of particles
      from nondirectional forces without using a bias, and are responsible for many
      types of biological transport, which occur with high yield despite strongly
      damped and noisy environments. Ratchets operate by breaking time-reversal and
      spatial symmetries in the direction of transport through application of a time
      dependent potential with repeating, asymmetric features. This work demonstrates
      the ratcheting of electrons within a highly scattering organic bulk
      heterojunction layer, and within a device architecture that enables the
      application of arbitrarily shaped oscillating electric potentials. Light is used
      to modulate the carrier density, which modifies the current with a nonmonotonic
      response predicted by theory. This system is driven with a single unbiased sine
      wave source, enabling the future use of natural oscillation sources such as
      electromagnetic radiation.

PMID- 28760956
TI  - Poly(ADP-ribose) polymerase 1 escorts XPC to UV-induced DNA lesions during
      nucleotide excision repair.
AB  - Xeroderma pigmentosum C (XPC) protein initiates the global genomic subpathway of
      nucleotide excision repair (GG-NER) for removal of UV-induced direct photolesions
      from genomic DNA. The XPC has an inherent capacity to identify and stabilize at
      the DNA lesion sites, and this function is facilitated in the genomic context by
      UV-damaged DNA-binding protein 2 (DDB2), which is part of a multiprotein UV-DDB
      ubiquitin ligase complex. The nuclear enzyme poly(ADP-ribose) polymerase 1
      (PARP1) has been shown to facilitate the lesion recognition step of GG-NER via
      its interaction with DDB2 at the lesion site. Here, we show that PARP1 plays an
      additional DDB2-independent direct role in recruitment and stabilization of XPC
      at the UV-induced DNA lesions to promote GG-NER. It forms a stable complex with
      XPC in the nucleoplasm under steady-state conditions before irradiation and
      rapidly escorts it to the damaged DNA after UV irradiation in a DDB2-independent
      manner. The catalytic activity of PARP1 is not required for the initial complex
      formation with XPC in the nucleoplasm but it enhances the recruitment of XPC to
      the DNA lesion site after irradiation. Using purified proteins, we also show that
      the PARP1-XPC complex facilitates the handover of XPC to the UV-lesion site in
      the presence of the UV-DDB ligase complex. Thus, the lesion search function of
      XPC in the genomic context is controlled by XPC itself, DDB2, and PARP1. Our
      results reveal a paradigm that the known interaction of many proteins with PARP1
      under steady-state conditions could have functional significance for these
      proteins.

PMID- 28760957
TI  - Hyperpolarized 13C MR metabolic imaging can detect neuroinflammation in vivo in a
      multiple sclerosis murine model.
AB  - Proinflammatory mononuclear phagocytes (MPs) play a crucial role in the
      progression of multiple sclerosis (MS) and other neurodegenerative diseases.
      Despite advances in neuroimaging, there are currently limited available methods
      enabling noninvasive detection of MPs in vivo. Interestingly, upon activation and
      subsequent differentiation toward a proinflammatory phenotype MPs undergo
      metabolic reprogramming that results in increased glycolysis and production of
      lactate. Hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging (MRSI)
      is a clinically translatable imaging method that allows noninvasive monitoring of
      metabolic pathways in real time. This method has proven highly useful to monitor
      the Warburg effect in cancer, through MR detection of increased HP [1
      13C]pyruvate-to-lactate conversion. However, to date, this method has never been
      applied to the study of neuroinflammation. Here, we questioned the potential of
      13C MRSI of HP [1-13C]pyruvate to monitor the presence of neuroinflammatory
      lesions in vivo in the cuprizone mouse model of MS. First, we demonstrated that
      13C MRSI could detect a significant increase in HP [1-13C]pyruvate-to-lactate
      conversion, which was associated with a high density of proinflammatory MPs. We
      further demonstrated that the increase in HP [1-13C]lactate was likely mediated
      by pyruvate dehydrogenase kinase 1 up-regulation in activated MPs, resulting in
      regional pyruvate dehydrogenase inhibition. Altogether, our results demonstrate a
      potential for 13C MRSI of HP [1-13C]pyruvate as a neuroimaging method for
      assessment of inflammatory lesions. This approach could prove useful not only in
      MS but also in other neurological diseases presenting inflammatory components.

PMID- 28760959
TI  - Lizards on newly created islands independently and rapidly adapt in morphology
      and diet.
AB  - Rapid adaptive changes can result from the drastic alterations humans impose on
      ecosystems. For example, flooding large areas for hydroelectric dams converts
      mountaintops into islands and leaves surviving populations in a new environment.
      We report differences in morphology and diet of the termite-eating gecko
      Gymnodactylus amarali between five such newly created islands and five nearby
      mainland sites located in the Brazilian Cerrado, a biodiversity hotspot. Mean
      prey size and dietary prey-size breadth were larger on islands than mainlands,
      expected because four larger lizard species that also consume termites, but
      presumably prefer larger prey, went extinct on the islands. In addition, island
      populations had larger heads relative to their body length than mainland
      populations; larger heads are more suited to the larger prey taken, and
      disproportionately larger heads allow that functional advantage without an
      increase in energetic requirements resulting from larger body size. Parallel
      morphological evolution is strongly suggested, because there are indications
      that, before flooding, relative head size did not differ between future island
      and future mainland sites. Females and males showed the same trend of relatively
      larger heads on islands, so the difference between island and mainland sites is
      unlikely to be due to greater male-male competition for mates on islands. We thus
      discovered a very fast (at most 15 y) case of independent parallel adaptive
      change in response to catastrophic human disturbance.

PMID- 28760958
TI  - Two interacting PPR proteins are major Arabidopsis editing factors in plastid and
      mitochondria.
AB  - RNA editing is converting hundreds of cytosines into uridines during organelle
      gene expression of land plants. The pentatricopeptide repeat (PPR) proteins are
      at the core of this posttranscriptional RNA modification. Even if a PPR protein
      defines the editing site, a DYW domain of the same or another PPR protein is
      believed to catalyze the deamination. To give insight into the organelle RNA
      editosome, we performed tandem affinity purification of the plastidial
      CHLOROPLAST BIOGENESIS 19 (CLB19) PPR editing factor. Two PPR proteins, dually
      targeted to mitochondria and chloroplasts, were identified as potential partners
      of CLB19. These two proteins, a P-type PPR and a member of a small PPR-DYW
      subfamily, were shown to interact in yeast. Insertional mutations resulted in
      embryo lethality that could be rescued by embryo-specific complementation. A
      transcriptome analysis of these complemented plants showed major editing defects
      in both organelles with a very high PPR type specificity, indicating that the two
      proteins are core members of E+-type PPR editosomes.

PMID- 28760961
TI  - Autonomous reciprocating migration of an active material.
AB  - Periodic to-and-fro migration is a sophisticated mode of locomotion found in many
      forms of active matter in nature. Providing a general description of periodic
      migration is challenging, because many details of animal migration remain a
      mystery. We study periodic migration in a simpler system using a mechanistic
      model of a photosensitive, active material in which a stimulus-responsive polymer
      gel is propelled by chemical waves under the regulation of an illumination
      gradient sensed by the gel, which plays a role analogous to the environment in
      periodic animal migration. The reciprocating gel migration results from
      autonomous transitions between retrograde and direct wave locomotion modes
      arising from the gradient distribution of the illumination intensity. The local
      dynamics of the chemical waves modulates the asymmetry between push and pull
      forces to achieve repeated reorientation of the direction of locomotion.
      Materials that display similar intelligent, self-adaptive locomotion might be
      tailored for such functions as drug delivery or self-cleaning systems.

PMID- 28760962
TI  - Correction for Breuer et al., System-wide organization of actin cytoskeleton
      determines organelle transport in hypocotyl plant cells.

PMID- 28760960
TI  - Oligomerization of the tetramerization domain of p53 probed by two- and three
      color single-molecule FRET.
AB  - We describe a method that combines two- and three-color single-molecule FRET
      spectroscopy with 2D FRET efficiency-lifetime analysis to probe the
      oligomerization process of intrinsically disordered proteins. This method is
      applied to the oligomerization of the tetramerization domain (TD) of the tumor
      suppressor protein p53. TD exists as a monomer at subnanomolar concentrations and
      forms a dimer and a tetramer at higher concentrations. Because the dissociation
      constants of the dimer and tetramer are very close, as we determine in this
      paper, it is not possible to characterize different oligomeric species by
      ensemble methods, especially the dimer that cannot be readily separated. However,
      by using single-molecule FRET spectroscopy that includes measurements of
      fluorescence lifetime and two- and three-color FRET efficiencies with corrections
      for submillisecond acceptor blinking, we show that it is possible to obtain
      structural information for individual oligomers at equilibrium and to determine
      the dimerization kinetics. From these analyses, we show that the monomer is
      intrinsically disordered and that the dimer conformation is very similar to that
      of the tetramer but the C terminus of the dimer is more flexible.

PMID- 28760964
TI  - Metal-mediated diradical tuning for DNA replication arrest via template strand
      scission.
AB  - A series of M(PyED).X (X = 2Cl-, SO42-) pyridine-metalloenediyne complexes [M =
      Cu(II), Fe(II), or Zn(II)] and their independently synthesized, cyclized analogs
      have been prepared to investigate their potential as radical-generating DNA
      damaging agents. All complexes possess a 1:1 metal-to-ligand stoichiometry as
      determined by electronic absorption spectroscopy and X-ray diffraction. Solution
      structural analysis reveals a ppi Cl [Formula: see text] Cu(II) LMCT (22,026 cm
      1) for Cu(PyED).2Cl, indicating three nitrogens and a chloride in the psuedo
      equatorial plane with the remaining pyridine nitrogen and solvent in axial
      positions. EPR spectra of the Cu(II) complexes exhibit an axially elongated
      octahedron. This spectroscopic evidence, together with density functional theory
      computed geometries, suggest six-coordinate structures for Cu(II) and Fe(II)
      complexes and a five-coordinate environment for Zn(II) analogs. Bergman
      cyclization via thermal activation of these constructs yields benzannulated
      product indicative of diradical generation in all complexes within 3 h at 37 
      degrees C. A significant metal dependence on the rate of the reaction is observed
      [Cu(II) > Fe(II) > Zn(II)], which is mirrored in in vitro DNA-damaging outcomes.
      Whereas in situ chelation of PyED leads to considerable degradation in the
      presence of all metals within 1 h under hyperthermia conditions, Cu(II)
      activation produces >50% compromised DNA within 5 min. Additionally, Cu(II)
      chelated PyED outcompetes DNA polymerase I to successfully inhibit template
      strand extension. Exposure of HeLa cells to Cu(PyBD).SO4 (IC50 = 10 MUM) results
      in a G2/M arrest compared with untreated samples, indicating significant DNA
      damage. These results demonstrate metal-controlled radical generation for
      degradation of biopolymers under physiologically relevant temperatures on short
      timescales.

PMID- 28760963
TI  - Atypical fracture with long-term bisphosphonate therapy is associated with
      altered cortical composition and reduced fracture resistance.
AB  - Bisphosphonates are the most widely prescribed pharmacologic treatment for
      osteoporosis and reduce fracture risk in postmenopausal women by up to 50%.
      However, in the past decade these drugs have been associated with atypical
      femoral fractures (AFFs), rare fractures with a transverse, brittle morphology.
      The unusual fracture morphology suggests that bisphosphonate treatment may impair
      toughening mechanisms in cortical bone. The objective of this study was to
      compare the compositional and mechanical properties of bone biopsies from
      bisphosphonate-treated patients with AFFs to those from patients with typical
      osteoporotic fractures with and without bisphosphonate treatment. Biopsies of
      proximal femoral cortical bone adjacent to the fracture site were obtained from
      postmenopausal women during fracture repair surgery (fracture groups, n = 33) or
      total hip arthroplasty (nonfracture groups, n = 17). Patients were allocated to
      five groups based on fracture morphology and history of bisphosphonate treatment
      [+BIS Atypical: n = 12, BIS duration: 8.2 (3.0) y; +BIS Typical: n = 10, 7.7
      (5.0) y; +BIS Nonfx: n = 5, 6.4 (3.5) y; -BIS Typical: n = 11; -BIS Nonfx: n =
      12]. Vibrational spectroscopy and nanoindentation showed that tissue from
      bisphosphonate-treated women with atypical fractures was harder and more
      mineralized than that from bisphosphonate-treated women with typical osteoporotic
      fractures. In addition, fracture mechanics measurements showed that tissue from
      patients treated with bisphosphonates had deficits in fracture toughness, with
      lower crack-initiation toughness and less crack deflection at osteonal boundaries
      than that of bisphosphonate-naive patients. Together, these results suggest a
      deficit in intrinsic and extrinsic toughening mechanisms, which contribute to
      AFFs in patients treated with long-term bisphosphonates.

PMID- 28760965
TI  - Quantitative time-resolved chemoproteomics reveals that stable O-GlcNAc regulates
      box C/D snoRNP biogenesis.
AB  - O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational
      modification on intracellular proteins, is dynamically regulated in cells. To
      analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a
      quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on
      metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable
      isotope labeling with amino acids in cell culture (SILAC). Applying qTOP, we
      quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and
      discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of
      protein backbones. The stability of those hyperstable O-GlcNAcylated proteins was
      more sensitive to O-GlcNAcylation inhibition compared with the more dynamic
      populations. Among the hyperstable population were three core proteins of box C/D
      small nucleolar ribonucleoprotein complexes (snoRNPs): fibrillarin (FBL),
      nucleolar protein 5A (NOP56), and nucleolar protein 5 (NOP58). We showed that O
      GlcNAcylation stabilized these proteins and was essential for snoRNP assembly.
      Blocking O-GlcNAcylation on FBL altered the 2'-O-methylation of rRNAs and
      impaired cancer cell proliferation and tumor formation in vivo.

PMID- 28760966
TI  - Neuronal cytoskeletal gene dysregulation and mechanical hypersensitivity in a rat
      model of Rett syndrome.
AB  - Children with Rett syndrome show abnormal cutaneous sensitivity. The precise
      nature of sensory abnormalities and underlying molecular mechanisms remain
      largely unknown. Rats with methyl-CpG binding protein 2 (MeCP2) mutation,
      characteristic of Rett syndrome, show hypersensitivity to pressure and cold, but
      hyposensitivity to heat. They also show cutaneous hyperinnervation by
      nonpeptidergic sensory axons, which include subpopulations encoding noxious
      mechanical and cold stimuli, whereas peptidergic thermosensory innervation is
      reduced. MeCP2 knockdown confined to dorsal root ganglion sensory neurons
      replicated this phenotype in vivo, and cultured MeCP2-deficient ganglion neurons
      showed augmented axonogenesis. Transcriptome analysis revealed dysregulation of
      genes associated with cytoskeletal dynamics, particularly those controlling actin
      polymerization and focal-adhesion formation necessary for axon growth and
      mechanosensory transduction. Down-regulation of these genes by topoisomerase
      inhibition prevented abnormal axon sprouting. We identified eight key affected
      genes controlling actin signaling and adhesion formation, including members of
      the Arhgap, Tiam, and cadherin families. Simultaneous virally mediated knockdown
      of these genes in Rett rats prevented sensory hyperinnervation and reversed
      mechanical hypersensitivity, indicating a causal role in abnormal outgrowth and
      sensitivity. Thus, MeCP2 regulates ganglion neuronal genes controlling
      cytoskeletal dynamics, which in turn determines axon outgrowth and mechanosensory
      function and may contribute to altered pain sensitivity in Rett syndrome.

PMID- 28760967
TI  - Deep evolutionary conservation of autism-related genes.
AB  - E. O. Wilson proposed in Sociobiology that similarities between human and animal
      societies reflect common mechanistic and evolutionary roots. When introduced in
      1975, this controversial hypothesis was beyond science's ability to test. We used
      genomic analyses to determine whether superficial behavioral similarities in
      humans and the highly social honey bee reflect common molecular mechanisms. Here,
      we report that gene expression signatures for individual bees unresponsive to
      various salient social stimuli are significantly enriched for autism spectrum
      disorder-related genes. These signatures occur in the mushroom bodies, a high
      level integration center of the insect brain. Furthermore, our finding of
      enrichment was unique to autism spectrum disorders; brain gene expression
      signatures from other honey bee behaviors do not show this enrichment, nor do
      datasets from other human behavioral and health conditions. These results
      demonstrate deep conservation for genes associated with a human social pathology
      and individual differences in insect social behavior, thus providing an example
      of how comparative genomics can be used to test sociobiological theory.

PMID- 28760968
TI  - Impact of glacial/interglacial sea level change on the ocean nitrogen cycle.
AB  - The continental shelves are the most biologically dynamic regions of the ocean,
      and they are extensive worldwide, especially in the western North Pacific. Their
      area has varied dramatically over the glacial/interglacial cycles of the last
      million years, but the effects of this variation on ocean biological and chemical
      processes remain poorly understood. Conversion of nitrate to N2 by
      denitrification in sediments accounts for half or more of the removal of
      biologically available nitrogen ("fixed N") from the ocean. The emergence of
      continental shelves during ice ages and their flooding during interglacials have
      been hypothesized to drive changes in sedimentary denitrification.
      Denitrification leads to the occurrence of phosphorus-bearing, N-depleted surface
      waters, which encourages N2 fixation, the dominant N input to the ocean. An
      860,000-y record of foraminifera shell-bound N isotopes from the South China Sea
      indicates that N2 fixation covaried with sea level. The N2 fixation changes are
      best explained as a response to changes in regional excess phosphorus supply due
      to sea level-driven variations in shallow sediment denitrification associated
      with the cyclic drowning and emergence of the continental shelves. This
      hypothesis is consistent with a glacial ocean that hosted globally lower rates of
      fixed N input and loss and a longer residence time for oceanic fixed N-a
      "sluggish" ocean N budget during ice ages. In addition, this work provides a
      clear sign of sea level-driven glacial/interglacial oscillations in
      biogeochemical fluxes at and near the ocean margins, with implications for
      coastal organisms and ecosystems.

PMID- 28760969
TI  - Factor-dependent archaeal transcription termination.
AB  - RNA polymerase activity is regulated by nascent RNA sequences, DNA template
      sequences, and conserved transcription factors. Transcription factors promoting
      initiation and elongation have been characterized in each domain, but
      transcription termination factors have been identified only in bacteria and
      eukarya. Here we describe euryarchaeal termination activity (Eta), the first
      archaeal termination factor capable of disrupting the transcription elongation
      complex (TEC), detail the rate of and requirements for Eta-mediated transcription
      termination, and describe a role for Eta in transcription termination in vivo.
      Eta-mediated transcription termination is energy-dependent, requires upstream DNA
      sequences, and disrupts TECs to release the nascent RNA to solution. Deletion of
      TK0566 (encoding Eta) is possible, but results in slow growth and renders cells
      sensitive to DNA damaging agents. Our results suggest that the mechanisms used by
      termination factors in archaea, eukarya, and bacteria to disrupt the TEC may be
      conserved, and that Eta stimulates release of stalled or arrested TECs.

PMID- 28760972
TI  - Printed droplet microfluidics for on demand dispensing of picoliter droplets and
      cells.
AB  - Although the elementary unit of biology is the cell, high-throughput methods for
      the microscale manipulation of cells and reagents are limited. The existing
      options either are slow, lack single-cell specificity, or use fluid volumes out
      of scale with those of cells. Here we present printed droplet microfluidics, a
      technology to dispense picoliter droplets and cells with deterministic control.
      The core technology is a fluorescence-activated droplet sorter coupled to a
      specialized substrate that together act as a picoliter droplet and single-cell
      printer, enabling high-throughput generation of intricate arrays of droplets,
      cells, and microparticles. Printed droplet microfluidics provides a programmable
      and robust technology to construct arrays of defined cell and reagent
      combinations and to integrate multiple measurement modalities together in a
      single assay.

PMID- 28760971
TI  - Cytokine signature associated with disease severity in chronic fatigue syndrome
      patients.
AB  - Although some signs of inflammation have been reported previously in patients
      with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are
      limited and contradictory. High-throughput methods now allow us to interrogate
      the human immune system for multiple markers of inflammation at a scale that was
      not previously possible. To determine whether a signature of serum cytokines
      could be associated with ME/CFS and correlated with disease severity and fatigue
      duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured
      using a 51-multiplex array on a Luminex system. Each cytokine's preprocessed data
      were regressed on ME/CFS severity plus covariates for age, sex, race, and an
      assay property of newly discovered importance: nonspecific binding. On average,
      TGF-beta was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in
      patients compared with controls. Seventeen cytokines had a statistically
      significant upward linear trend that correlated with ME/CFS severity: CCL11
      (Eotaxin-1), CXCL1 (GROalpha), CXCL10 (IP-10), IFN-gamma, IL-4, IL-5, IL-7, IL
      12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-alpha. Of the
      17 cytokines that correlated with severity, 13 are proinflammatory, likely
      contributing to many of the symptoms experienced by patients and establishing a
      strong immune system component of the disease. Only CXCL9 (MIG) inversely
      correlated with fatigue duration.

PMID- 28760970
TI  - Habitual sleep as a contributor to racial differences in cardiometabolic risk.
AB  - Insufficient and disrupted sleep is linked with cardiovascular and metabolic
      dysregulation and morbidity. The current study examines the degree to which
      differences in sleep between black/African American (AA) and white/European
      American (EA) adults explain racial differences in cardiometabolic (CMB) disease
      risk. Total sleep time and sleep efficiency (percent of time in bed asleep) were
      assessed via seven nights of wrist actigraphy among 426 participants in the
      Midlife in the United States Study (31% AA; 69% EA; 61% female; mean age = 56.8
      y). CMB risk was indexed as a composite of seven biomarkers [blood pressure,
      waist circumference, hemoglobin A1c (HbA1c), insulin resistance, triglycerides,
      HDL cholesterol (HDL-C), and C-reactive protein]. Covariates included
      sociodemographic characteristics and relevant health behaviors. Results indicated
      that AAs relative to EAs obtained less sleep (341 vs. 381 min) and had lower
      sleep efficiency (72.3 vs. 82.2%) (P values < 0.001). Further, 41% and 58% of the
      racial difference in CMB risk was explained by sleep time and sleep efficiency,
      respectively. In models stratified by sex, race was indirectly associated with
      CMB risk via sleep time and efficiency only among females (explaining 33% and 65%
      of the race difference, respectively). Indirect effects were robust to
      alternative model specifications that excluded participants with diabetes or
      heart disease. Consideration of sleep determinants and sleep health is therefore
      needed in efforts to reduce racial differences in CMB disease.

PMID- 28760973
TI  - Plant feeding promotes diversification in the Crustacea.
AB  - About half of the world's animal species are arthropods associated with plants,
      and the ability to consume plant material has been proposed to be an important
      trait associated with the spectacular diversification of terrestrial insects. We
      review the phylogenetic distribution of plant feeding in the Crustacea, the other
      major group of arthropods that commonly consume plants, to estimate how often
      plant feeding has arisen and to test whether this dietary transition is
      associated with higher species numbers in extant clades. We present evidence that
      at least 31 lineages of marine, freshwater, and terrestrial crustaceans
      (including 64 families and 185 genera) have independently overcome the challenges
      of consuming plant material. These plant-feeding clades are, on average, 21-fold
      more speciose than their sister taxa, indicating that a shift in diet is
      associated with increased net rates of diversification. In contrast to
      herbivorous insects, most crustaceans have very broad diets, and the increased
      richness of taxa that include plants in their diet likely results from access to
      a novel resource base rather than host-associated divergence.

PMID- 28760975
TI  - Concurrent design of quasi-random photonic nanostructures.
AB  - Nanostructured surfaces with quasi-random geometries can manipulate light over
      broadband wavelengths and wide ranges of angles. Optimization and realization of
      stochastic patterns have typically relied on serial, direct-write fabrication
      methods combined with real-space design. However, this approach is not suitable
      for customizable features or scalable nanomanufacturing. Moreover, trial-and
      error processing cannot guarantee fabrication feasibility because processing
      structure relations are not included in conventional designs. Here, we report
      wrinkle lithography integrated with concurrent design to produce quasi-random
      nanostructures in amorphous silicon at wafer scales that achieved over 160% light
      absorption enhancement from 800 to 1,200 nm. The quasi-periodicity of patterns,
      materials filling ratio, and feature depths could be independently controlled. We
      statistically represented the quasi-random patterns by Fourier spectral density
      functions (SDFs) that could bridge the processing-structure and structure
      performance relations. Iterative search of the optimal structure via the SDF
      representation enabled concurrent design of nanostructures and processing.

PMID- 28760974
TI  - Structural basis of subunit selectivity for competitive NMDA receptor antagonists
      with preference for GluN2A over GluN2B subunits.
AB  - NMDA-type glutamate receptors are ligand-gated ion channels that contribute to
      excitatory neurotransmission in the central nervous system (CNS). Most NMDA
      receptors comprise two glycine-binding GluN1 and two glutamate-binding GluN2
      subunits (GluN2A-D). We describe highly potent (S)-5-[(R)-2-amino-2-carboxyethyl]
      4,5-dihydro-1H-pyrazole-3-carboxylic acid (ACEPC) competitive GluN2 antagonists,
      of which ST3 has a binding affinity of 52 nM at GluN1/2A and 782 nM at GluN1/2B
      receptors. This 15-fold preference of ST3 for GluN1/2A over GluN1/2B is improved
      compared with NVP-AAM077, a widely used GluN2A-selective antagonist, which we
      show has 11-fold preference for GluN1/2A over GluN1/2B. Crystal structures of the
      GluN1/2A agonist binding domain (ABD) heterodimer with bound ACEPC antagonists
      reveal a binding mode in which the ligands occupy a cavity that extends toward
      the subunit interface between GluN1 and GluN2A ABDs. Mutational analyses show
      that the GluN2A preference of ST3 is primarily mediated by four nonconserved
      residues that are not directly contacting the ligand, but positioned within 12 A
      of the glutamate binding site. Two of these residues influence the cavity
      occupied by ST3 in a manner that results in favorable binding to GluN2A, but
      occludes binding to GluN2B. Thus, we reveal opportunities for the design of
      subunit-selective competitive NMDA receptor antagonists by identifying a cavity
      for ligand binding in which variations exist between GluN2A and GluN2B subunits.
      This structural insight suggests that subunit selectivity of glutamate-site
      antagonists can be mediated by mechanisms in addition to direct contributions of
      contact residues to binding affinity.

PMID- 28760976
TI  - Elevated IOP alters the space-time profiles in the center and surround of both ON
      and OFF RGCs in mouse.
AB  - Glaucoma is a leading cause of blindness worldwide, and is characterized by
      progressive retinal ganglion cell (RGC) death. An experimental model of glaucoma
      has been established by elevating the intraocular pressure (IOP) via microbead
      occlusion of ocular fluid outflow in mice. Studies in this model have found
      visual dysfunction that varied with adaptational state, occurred before
      anatomical changes, and affected OFF RGCs more than ON RGCs. These results
      indicate subtle alterations in the underlying retinal circuitry that could help
      identify disease before irreversible RGC changes. Therefore, we looked at how RGC
      function was altered with elevated IOP under both photopic and scotopic
      conditions. We first found that responses to light offset are diminished with IOP
      elevation along with a concomitant decrease in receptive field center size for
      OFF RGCs. In addition, the antagonistic surround strength and size was reduced in
      ON RGCs. Furthermore, elevation of IOP significantly accelerated the photopic
      temporal tuning of RGC center responses in both ON and OFF RGCs. We found that
      some of the IOP-induced functional changes to OFF RGCs relied on ON cross-over
      pathways, indicating dysfunction in inner retinal circuitry. Overall, these
      results suggest that IOP alters multiple functions in the retina depending on the
      adaptational state. They provide a basis for designing multiple functional tests
      for early detection of glaucoma and for circuit-specific therapeutic targets in
      treatment of this blinding disease.

PMID- 28760977
TI  - Molecular characterization of water and surfactant AOT at nanoemulsion surfaces.
AB  - Nanoemulsions and microemulsions are environments where oil and water can be
      solubilized in one another to provide a unique platform for many different
      biological and industrial applications. Nanoemulsions, unlike microemulsions,
      have seen little work done to characterize molecular interactions at their
      surfaces. This study provides a detailed investigation of the near-surface
      molecular structure of regular (oil in water) and reverse (water in oil)
      nanoemulsions stabilized with the surfactant dioctyl sodium sulfosuccinate (AOT).
      Vibrational sum-frequency scattering spectroscopy (VSFSS) is used to measure the
      vibrational spectroscopy of these AOT stabilized regular and reverse
      nanoemulsions. Complementary studies of AOT adsorbed at the planar oil-water
      interface are conducted with vibrational sum-frequency spectroscopy (VSFS).
      Jointly, these give comparative insights into the orientation of interfacial
      water and the molecular characterization of the hydrophobic and hydrophilic
      regions of AOT at the different oil-water interfaces. Whereas the polar region of
      AOT and surrounding interfacial water molecules display nearly identical behavior
      at both the planar and droplet interface, there is a clear difference in
      hydrophobic chain ordering even when possible surface concentration differences
      are taken into account. This chain ordering is found to be invariant as the
      nanodroplets grow by Ostwald ripening and also with substitution of different
      counterions (Na:AOT, K:AOT, and Mg:AOT) that consequently also result in
      different sized nanoparticles. The results paint a compelling picture of
      surfactant assembly at these relatively large nanoemulsion surfaces and allow for
      an important comparison of AOT at smaller micellar (curved) and planar oil-water
      interfaces.

PMID- 28760978
TI  - Superresolution expansion microscopy reveals the three-dimensional organization
      of the Drosophila synaptonemal complex.
AB  - The synaptonemal complex (SC), a structure highly conserved from yeast to
      mammals, assembles between homologous chromosomes and is essential for accurate
      chromosome segregation at the first meiotic division. In Drosophila melanogaster,
      many SC components and their general positions within the complex have been
      dissected through a combination of genetic analyses, superresolution microscopy,
      and electron microscopy. Although these studies provide a 2D understanding of SC
      structure in Drosophila, the inability to optically resolve the minute distances
      between proteins in the complex has precluded its 3D characterization. A recently
      described technology termed expansion microscopy (ExM) uniformly increases the
      size of a biological sample, thereby circumventing the limits of optical
      resolution. By adapting the ExM protocol to render it compatible with structured
      illumination microscopy, we can examine the 3D organization of several known
      Drosophila SC components. These data provide evidence that two layers of SC are
      assembled. We further speculate that each SC layer may connect two nonsister
      chromatids, and present a 3D model of the Drosophila SC based on these findings.

PMID- 28760980
TI  - QnAs with Luciana Borio.

PMID- 28760979
TI  - Phospholipase A activity of adenylate cyclase toxin mediates translocation of its
      adenylate cyclase domain.
AB  - Adenylate cyclase toxin (ACT or CyaA) plays a crucial role in respiratory tract
      colonization and virulence of the whooping cough causative bacterium Bordetella
      pertussis Secreted as soluble protein, it targets myeloid cells expressing the
      CD11b/CD18 integrin and on delivery of its N-terminal adenylate cyclase catalytic
      domain (AC domain) into the cytosol, generates uncontrolled toxic levels of cAMP
      that ablates bactericidal capacities of phagocytes. Our study deciphers the
      fundamentals of the heretofore poorly understood molecular mechanism by which the
      ACT enzyme domain directly crosses the host cell membrane. By combining molecular
      biology, biochemistry, and biophysics techniques, we discover that ACT has
      intrinsic phospholipase A (PLA) activity, and that such activity determines AC
      translocation. Moreover, we show that elimination of the ACT-PLA activity
      abrogates ACT toxicity in macrophages, particularly at toxin concentrations close
      to biological reality of bacterial infection. Our data support a molecular
      mechanism in which in situ generation of nonlamellar lysophospholipids by ACT-PLA
      activity into the cell membrane would form, likely in combination with membrane
      interacting ACT segments, a proteolipidic toroidal pore through which AC domain
      transfer could directly take place. Regulation of ACT-PLA activity thus emerges
      as novel target for therapeutic control of the disease.

PMID- 28760981
TI  - Three Cambrian fossils assembled into an extinct body plan of cnidarian affinity.
AB  - The early Cambrian problematica Xianguangia sinica, Chengjiangopenna wangii, and
      Galeaplumosus abilus from the Chengjiang biota (Yunnan, China) have caused much
      controversy in the past and their phylogenetic placements remain unresolved. Here
      we show, based on exceptionally preserved material (85 new specimens plus type
      material), that specimens previously assigned to these three species are in fact
      parts of the same organism and propose that C. wangii and G. abilus are junior
      synonyms of X. sinica Our reconstruction of the complete animal reveals an
      extinct body plan that combines the characteristics of the three described
      species and is distinct from all known fossil and living taxa. This animal
      resembled a cnidarian polyp in overall morphology and having a gastric cavity
      partitioned by septum-like structures. However, it possessed an additional body
      cavity within its holdfast, an anchoring pit on the basal disk, and feather-like
      tentacles with densely ciliated pinnules arranged in an alternating pattern,
      indicating that it was a suspension feeder rather than a predatory actiniarian.
      Phylogenetic analyses using Bayesian inference and maximum parsimony suggest that
      X. sinica is a stem-group cnidarian. This relationship implies that the last
      common ancestor of X. sinica and crown cnidarians was probably a benthic,
      polypoid animal with a partitioned gastric cavity and a single mouth/anus
      opening. This extinct body plan suggests that feeding strategies of stem
      cnidarians may have been drastically different from that of their crown
      relatives, which are almost exclusively predators, and reveals that the
      morphological disparity of total-group Cnidaria is greater than previously
      assumed.

PMID- 28760984
TI  - QnAs with Joe Lutkenhaus.

PMID- 28760982
TI  - Low-frequency hippocampal-cortical activity drives brain-wide resting-state
      functional MRI connectivity.
AB  - The hippocampus, including the dorsal dentate gyrus (dDG), and cortex engage in
      bidirectional communication. We propose that low-frequency activity in
      hippocampal-cortical pathways contributes to brain-wide resting-state
      connectivity to integrate sensory information. Using optogenetic stimulation and
      brain-wide fMRI and resting-state fMRI (rsfMRI), we determined the large-scale
      effects of spatiotemporal-specific downstream propagation of hippocampal
      activity. Low-frequency (1 Hz), but not high-frequency (40 Hz), stimulation of
      dDG excitatory neurons evoked robust cortical and subcortical brain-wide fMRI
      responses. More importantly, it enhanced interhemispheric rsfMRI connectivity in
      various cortices and hippocampus. Subsequent local field potential recordings
      revealed an increase in slow oscillations in dorsal hippocampus and visual
      cortex, interhemispheric visual cortical connectivity, and hippocampal-cortical
      connectivity. Meanwhile, pharmacological inactivation of dDG neurons decreased
      interhemispheric rsfMRI connectivity. Functionally, visually evoked fMRI
      responses in visual regions also increased during and after low-frequency dDG
      stimulation. Together, our results indicate that low-frequency activity robustly
      propagates in the dorsal hippocampal-cortical pathway, drives interhemispheric
      cortical rsfMRI connectivity, and mediates visual processing.

PMID- 28760983
TI  - Crop-damaging temperatures increase suicide rates in India.
AB  - More than three quarters of the world's suicides occur in developing countries,
      yet little is known about the drivers of suicidal behavior in poor populations. I
      study India, where one fifth of global suicides occur and suicide rates have
      doubled since 1980. Using nationally comprehensive panel data over 47 y, I
      demonstrate that fluctuations in climate, particularly temperature, significantly
      influence suicide rates. For temperatures above 20  degrees C, a 1  degrees C
      increase in a single day's temperature causes ~70 suicides, on average. This
      effect occurs only during India's agricultural growing season, when heat also
      lowers crop yields. I find no evidence that acclimatization, rising incomes, or
      other unobserved drivers of adaptation are occurring. I estimate that warming
      over the last 30 y is responsible for 59,300 suicides in India, accounting for
      6.8% of the total upward trend. These results deliver large-scale quantitative
      evidence linking climate and agricultural income to self-harm in a developing
      country.

PMID- 28760985
TI  - Distinct functions of diaphanous-related formins regulate HIV-1 uncoating and
      transport.
AB  - Diaphanous (Dia)-related formins (DRFs) coordinate cytoskeletal remodeling by
      controlling actin nucleation and microtubule (MT) stabilization to facilitate
      processes such as cell polarization and migration; yet the full extent of their
      activities remains unknown. Here, we uncover two discrete roles and functions of
      DRFs during early human immunodeficiency virus type 1 (HIV-1) infection.
      Independent of their actin regulatory activities, Dia1 and Dia2 facilitated HIV-1
      induced MT stabilization and the intracellular motility of virus particles.
      However, DRFs also bound in vitro assembled capsid-nucleocapsid complexes and
      promoted the disassembly of HIV-1 capsid (CA) shell. This process, also known as
      "uncoating," is among the most poorly understood stages in the viral lifecycle.
      Domain analysis and structure modeling revealed that regions of Dia2 that bound
      viral CA and mediated uncoating as well as early infection contained coiled-coil
      domains, and that these activities were genetically separable from effects on MT
      stabilization. Our findings reveal that HIV-1 exploits discrete functions of DRFs
      to coordinate critical steps in early infection and identifies Dia family members
      as regulators of the poorly understood process of HIV-1 uncoating.

PMID- 28760987
TI  - Toll-like receptor 4 deficiency alters nucleus accumbens synaptic physiology and
      drug reward behavior.
AB  - Behavioral manifestations of drug-seeking behavior are causally linked to
      alterations of synaptic strength onto nucleus accumbens (NAc) medium spiny
      neurons (MSN). Although neuron-driven changes in physiology and behavior are well
      characterized, there is a lack of knowledge of the role of the immune system in
      mediating such effects. Toll-like receptor 4 (TLR4) is a pattern recognition
      molecule of the innate immune system, and evidence suggests that it modulates
      drug-related behavior. Using TLR4 knockout (TLR4.KO) mice, we show that TLR4
      plays a role in NAc synaptic physiology and behavior. In addition to differences
      in the pharmacological profile of N-methyl-d-aspartate receptors (NMDAR) in the
      NAc core, TLR4.KO animals exhibit a deficit in low-frequency stimulation-induced
      NMDAR-dependent long-term depression (LTD). Interestingly, the synaptic
      difference is region specific as no differences were found in excitatory synaptic
      properties in the NAc shell. Consistent with altered NAc LTD, TLR4.KO animals
      exhibit an attenuation in drug reward learning. Finally, we show that TLR4 in the
      NAc core is primarily expressed on microglia. These results suggest that TLR4
      influences NAc MSN synaptic physiology and drug reward learning and behavior.

PMID- 28760986
TI  - PUM1 is a biphasic negative regulator of innate immunity genes by suppressing
      LGP2.
AB  - PUM1 is an RNA binding protein shown to regulate the stability and function of
      mRNAs bearing a specific sequence. We report the following: (i) A key function of
      PUM1 is that of a repressor of key innate immunity genes by repressing the
      expression of LGP2. Thus, between 12 and 48 hours after transfection of human
      cells with siPUM1 RNA there was an initial (phase 1) upsurge of transcripts
      encoding LGP2, CXCL10, IL6, and PKR. This was followed 24 hours later (phase 2)
      by a significant accumulation of mRNAs encoding RIG-I, SP100, MDA5, IFIT1, PML,
      STING, and IFNbeta. The genes that were not activated encoded HDAC4 and NF
      kappaB1. (ii) Simultaneous depletion of PUM1 and LGP2, CXCL10, or IL6 revealed
      that up-regulation of phase 1 and phase 2 genes was the consequence of up
      regulation of LGP2. (iii) IFNbeta produced 48-72 hours after transfection of
      siPUM1 was effective in up-regulating LGP2 and phase 2 genes and reducing the
      replication of HSV-1 in untreated cells. (iv) Because only half of genes up
      regulated in phase 1 and 2 encode mRNAs containing PUM1 binding sites, the
      upsurge in gene expression could not be attributed solely to stabilization of
      mRNAs in the absence of PUM1. (v) Lastly, depletion of PUM2 does not result in up
      regulation of phase 1 or phase 2 genes. The results of the studies presented here
      indicate that PUM1 is a negative regulator of LGP2, a master regulator of innate
      immunity genes expressed in a cascade fashion.

PMID- 28760988
TI  - Ultralow thermal conductivity in all-inorganic halide perovskites.
AB  - Controlling the flow of thermal energy is crucial to numerous applications
      ranging from microelectronic devices to energy storage and energy conversion
      devices. Here, we report ultralow lattice thermal conductivities of solution
      synthesized, single-crystalline all-inorganic halide perovskite nanowires
      composed of CsPbI3 (0.45 +/- 0.05 W.m-1.K-1), CsPbBr3 (0.42 +/- 0.04 W.m-1.K-1),
      and CsSnI3 (0.38 +/- 0.04 W.m-1.K-1). We attribute this ultralow thermal
      conductivity to the cluster rattling mechanism, wherein strong optical-acoustic
      phonon scatterings are driven by a mixture of 0D/1D/2D collective motions.
      Remarkably, CsSnI3 possesses a rare combination of ultralow thermal conductivity,
      high electrical conductivity (282 S.cm-1), and high hole mobility (394 cm2.V-1.s
      1). The unique thermal transport properties in all-inorganic halide perovskites
      hold promise for diverse applications such as phononic and thermoelectric
      devices. Furthermore, the insights obtained from this work suggest an opportunity
      to discover low thermal conductivity materials among unexplored inorganic
      crystals beyond caged and layered structures.

PMID- 28760989
TI  - Time-resolved observation of protein allosteric communication.
AB  - Allostery represents a fundamental mechanism of biological regulation that is
      mediated via long-range communication between distant protein sites. Although
      little is known about the underlying dynamical process, recent time-resolved
      infrared spectroscopy experiments on a photoswitchable PDZ domain (PDZ2S) have
      indicated that the allosteric transition occurs on multiple timescales. Here,
      using extensive nonequilibrium molecular dynamics simulations, a time-dependent
      picture of the allosteric communication in PDZ2S is developed. The simulations
      reveal that allostery amounts to the propagation of structural and dynamical
      changes that are genuinely nonlinear and can occur in a nonlocal fashion. A
      dynamic network model is constructed that illustrates the hierarchy and exceeding
      structural heterogeneity of the process. In compelling agreement with experiment,
      three physically distinct phases of the time evolution are identified, describing
      elastic response ([Formula: see text] ns), inelastic reorganization ([Formula:
      see text] ns), and structural relaxation ([Formula: see text]s). Issues such as
      the similarity to downhill folding as well as the interpretation of allosteric
      pathways are discussed.

PMID- 28760990
TI  - Engineering the lutein epoxide cycle into Arabidopsis thaliana.
AB  - Although sunlight provides the energy necessary for plants to survive and grow,
      light can also damage reaction centers of photosystem II (PSII) and reduce
      photochemical efficiency. To prevent damage, plants possess photoprotective
      mechanisms that dissipate excess excitation. A subset of these mechanisms is
      collectively referred to as NPQ, or nonphotochemical quenching of chlorophyll a
      fluorescence. The regulation of NPQ is intrinsically linked to the cycling of
      xanthophylls that affects the kinetics and extent of the photoprotective
      response. The violaxanthin cycle (VAZ cycle) and the lutein epoxide cycle (LxL
      cycle) are two xanthophyll cycles found in vascular plants. The VAZ cycle has
      been studied extensively, owing in large part to its presence in model plant
      species where mutants are available to aid in its characterization. In contrast,
      the LxL cycle is not found in model plants, and its role in photosynthetic
      processes has been more difficult to define. To address this challenge, we
      introduced the LxL cycle into Arabidopsis thaliana and functionally isolated it
      from the VAZ cycle. Using these plant lines, we showed an increase in dark
      acclimated PSII efficiency associated with Lx accumulation and demonstrated that
      violaxanthin deepoxidase is responsible for the light-driven deepoxidation of Lx.
      Conversion of Lx to L was reversible during periods of low light and occurred
      considerably faster than rates previously described in nonmodel species. Finally,
      we present clear evidence of the LxL cycle's role in modulating a rapid component
      of NPQ that is necessary to prevent photoinhibition in excess light.

PMID- 28760991
TI  - Presumptive TRP channel CED-11 promotes cell volume decrease and facilitates
      degradation of apoptotic cells in Caenorhabditis elegans.
AB  - Apoptotic cells undergo a series of morphological changes. These changes are
      dependent on caspase cleavage of downstream targets, but which targets are
      significant and how they facilitate the death process are not well understood. In
      Caenorhabditis elegans an increase in the refractility of the dying cell is a
      hallmark morphological change that is caspase dependent. We identify a
      presumptive transient receptor potential (TRP) cation channel, CED-11, that acts
      in the dying cell to promote the increase in apoptotic cell refractility. CED-11
      is required for multiple other morphological changes during apoptosis, including
      an increase in electron density as visualized by electron microscopy and a
      decrease in cell volume. In ced-11 mutants, the degradation of apoptotic cells is
      delayed. Mutation of ced-11 does not cause an increase in cell survival but can
      enhance cell survival in other cell-death mutants, indicating that ced-11
      facilitates the death process. In short, ced-11 acts downstream of caspase
      activation to promote the shrinkage, death, and degradation of apoptotic cells.

PMID- 28760992
TI  - Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone
      receptor pathway.
AB  - Nuclear receptors play important roles in regulating fat metabolism and energy
      production in humans. The regulatory functions and endogenous ligands of many
      nuclear receptors are still unidentified, however. Here, we report that CYP-37A1
      (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450
      oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR)
      constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis
      elegans This pathway specifically regulates the thermosensitive fusion of fat
      storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic
      hormone not identical to Delta7-dafachronic acid, which represses the fusion
      promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance
      and lifespan at high temperature in a DAF-12-dependent manner. Human CYP4V2 can
      substitute for CYP-37A1 in C. elegans This finding suggests the existence of a
      conserved CYP4V2-POR-nuclear receptor pathway that functions in converting
      multilocular lipid droplets to unilocular ones in human cells; misregulation of
      this pathway may lead to pathogenic fat storage.

PMID- 28760993
TI  - Interferon-gamma is a master checkpoint regulator of cytokine-induced
      differentiation.
AB  - Cytokines are protein mediators that are known to be involved in many biological
      processes, including cell growth, survival, inflammation, and development. To
      study their regulation, we generated a library of 209 different cytokines. This
      was used in a combinatorial format to study the effects of cytokines on each
      other, with particular reference to the control of differentiation. This study
      showed that IFN-gamma is a master checkpoint regulator for many cytokines. It
      operates via an autocrine mechanism to elevate STAT1 and induce internalization
      of gp130, a common component of many heterodimeric cytokine receptors. This
      targeting of a receptor subunit that is common to all members of an otherwise
      diverse family solves the problem of how a master regulator can control so many
      diverse receptors. When one adds an autocrine mechanism, fine control at the
      level of individual cells is achieved.

PMID- 28760994
TI  - Atomic structure of a toxic, oligomeric segment of SOD1 linked to amyotrophic
      lateral sclerosis (ALS).
AB  - Fibrils and oligomers are the aggregated protein agents of neuronal dysfunction
      in ALS diseases. Whereas we now know much about fibril architecture, atomic
      structures of disease-related oligomers have eluded determination. Here, we
      determine the corkscrew-like structure of a cytotoxic segment of superoxide
      dismutase 1 (SOD1) in its oligomeric state. Mutations that prevent formation of
      this structure eliminate cytotoxicity of the segment in isolation as well as
      cytotoxicity of the ALS-linked mutants of SOD1 in primary motor neurons and in a
      Danio rerio (zebrafish) model of ALS. Cytotoxicity assays suggest that toxicity
      is a property of soluble oligomers, and not large insoluble aggregates. Our work
      adds to evidence that the toxic oligomeric entities in protein aggregation
      diseases contain antiparallel, out-of-register beta-sheet structures and
      identifies a target for structure-based therapeutics in ALS.

PMID- 28760995
TI  - SPF45-related splicing factor for phytochrome signaling promotes
      photomorphogenesis by regulating pre-mRNA splicing in Arabidopsis.
AB  - Light signals regulate plant growth and development by controlling a plethora of
      gene expression changes. Posttranscriptional regulation, especially pre-mRNA
      processing, is a key modulator of gene expression; however, the molecular
      mechanisms linking pre-mRNA processing and light signaling are not well
      understood. Here we report a protein related to the human splicing factor 45
      (SPF45) named splicing factor for phytochrome signaling (SFPS), which directly
      interacts with the photoreceptor phytochrome B (phyB). In response to light, SFPS
      RFP (red fluorescent protein) colocalizes with phyB-GFP in photobodies. sfps loss
      of-function plants are hyposensitive to red, far-red, and blue light, and flower
      precociously. SFPS colocalizes with U2 small nuclear ribonucleoprotein-associated
      factors including U2AF65B, U2A', and U2AF35A in nuclear speckles, suggesting SFPS
      might be involved in the 3' splice site determination. SFPS regulates pre-mRNA
      splicing of a large number of genes, of which many are involved in regulating
      light signaling, photosynthesis, and the circadian clock under both dark and
      light conditions. In vivo RNA immunoprecipitation (RIP) assays revealed that SFPS
      associates with EARLY FLOWERING 3 (ELF3) mRNA, a critical link between light
      signaling and the circadian clock. Moreover, PHYTOCHROME INTERACTING FACTORS
      (PIFs) transcription factor genes act downstream of SFPS, as the quadruple pif
      mutant pifq suppresses defects of sfps mutants. Taken together, these data
      strongly suggest SFPS modulates light-regulated developmental processes by
      controlling pre-mRNA splicing of light signaling and circadian clock genes.

PMID- 28760997
TI  - Empirical prediction intervals improve energy forecasting.
AB  - Hundreds of organizations and analysts use energy projections, such as those
      contained in the US Energy Information Administration (EIA)'s Annual Energy
      Outlook (AEO), for investment and policy decisions. Retrospective analyses of
      past AEO projections have shown that observed values can differ from the
      projection by several hundred percent, and thus a thorough treatment of
      uncertainty is essential. We evaluate the out-of-sample forecasting performance
      of several empirical density forecasting methods, using the continuous ranked
      probability score (CRPS). The analysis confirms that a Gaussian density,
      estimated on past forecasting errors, gives comparatively accurate uncertainty
      estimates over a variety of energy quantities in the AEO, in particular
      outperforming scenario projections provided in the AEO. We report probabilistic
      uncertainties for 18 core quantities of the AEO 2016 projections. Our work frames
      how to produce, evaluate, and rank probabilistic forecasts in this setting. We
      propose a log transformation of forecast errors for price projections and a
      modified nonparametric empirical density forecasting method. Our findings give
      guidance on how to evaluate and communicate uncertainty in future energy
      outlooks.

PMID- 28760996
TI  - Ensemble modeling informs hypoxia management in the northern Gulf of Mexico.
AB  - A large region of low-dissolved-oxygen bottom waters (hypoxia) forms nearly every
      summer in the northern Gulf of Mexico because of nutrient inputs from the
      Mississippi River Basin and water column stratification. Policymakers developed
      goals to reduce the area of hypoxic extent because of its ecological, economic,
      and commercial fisheries impacts. However, the goals remain elusive after 30 y of
      research and monitoring and 15 y of goal-setting and assessment because there has
      been little change in river nitrogen concentrations. An intergovernmental Task
      Force recently extended to 2035 the deadline for achieving the goal of a 5,000
      km2 5-y average hypoxic zone and set an interim load target of a 20% reduction of
      the spring nitrogen loading from the Mississippi River by 2025 as part of their
      adaptive management process. The Task Force has asked modelers to reassess the
      loading reduction required to achieve the 2035 goal and to determine the effect
      of the 20% interim load reduction. Here, we address both questions using a
      probabilistic ensemble of four substantially different hypoxia models. Our
      results indicate that, under typical weather conditions, a 59% reduction in
      Mississippi River nitrogen load is required to reduce hypoxic area to 5,000 km2
      The interim goal of a 20% load reduction is expected to produce an 18% reduction
      in hypoxic area over the long term. However, due to substantial interannual
      variability, a 25% load reduction is required before there is 95% certainty of
      observing any hypoxic area reduction between consecutive 5-y assessment periods.

PMID- 28760998
TI  - Engineered gray mold resistance, antioxidant capacity, and pigmentation in
      betalain-producing crops and ornamentals.
AB  - Betalains are tyrosine-derived red-violet and yellow plant pigments known for
      their antioxidant activity, health-promoting properties, and wide use as food
      colorants and dietary supplements. By coexpressing three genes of the recently
      elucidated betalain biosynthetic pathway, we demonstrate the heterologous
      production of these pigments in a variety of plants, including three major food
      crops: tomato, potato, and eggplant, and the economically important ornamental
      petunia. Combinatorial expression of betalain-related genes also allowed the
      engineering of tobacco plants and cell cultures to produce a palette of unique
      colors. Furthermore, betalain-producing tobacco plants exhibited significantly
      increased resistance toward gray mold (Botrytis cinerea), a pathogen responsible
      for major losses in agricultural produce. Heterologous production of betalains is
      thus anticipated to enable biofortification of essential foods, development of
      new ornamental varieties, and innovative sources for commercial betalain
      production, as well as utilization of these pigments in crop protection.

PMID- 28760999
TI  - Exploiting conformational plasticity in the AAA+ protein VCP/p97 to modify
      function.
AB  - p97/VCP, a member of the AAA+ (ATPases associated with diverse cellular
      activities) family of proteins, is implicated in the etiology of a group of
      degenerative diseases affecting bone and muscle tissue as well as the central
      nervous system. Methyl-TROSY-based NMR studies have previously revealed how
      disease-causing mutations deregulate a subtle dynamic conformational equilibrium
      involving the N-terminal domain (NTD) with implications for the binding of
      certain adaptors, providing insight into how disease mutations lead to abnormal
      function. Herein the conformational plasticity of the p97 system is explored in
      an attempt to identify hotspots that can serve as targets for restoring function
      in disease mutants by shifting the position of the NTD back to its wild-type
      location. Although p97 is overall robust with respect to extensive mutagenesis
      throughout the protein involving conservative substitutions of hydrophobic
      residues, key positions have been identified that alter the NTD equilibrium;
      these lie in specific regions that localize to the interface between the NTD and
      the D1 nucleotide-binding domain of the complex. Notably, for a severe disease
      mutant involving an R155C substitution the NTD equilibrium can be shifted back to
      its wild-type position by mutation at a secondary site with restoration of wild
      type two-pronged binding of the UBXD1 adaptor protein that is impaired in
      disease; this underlies the potential for recovering function by targeting p97
      disease mutants with drug molecules.

PMID- 28761000
TI  - Elevated auxin biosynthesis and transport underlie high vein density in C4
      leaves.
AB  - High vein density, a distinctive trait of C4 leaves, is central to both C3-to-C4
      evolution and conversion of C3 to C4-like crops. We tested the hypothesis that
      high vein density in C4 leaves is due to elevated auxin biosynthesis and
      transport in developing leaves. Up-regulation of genes in auxin biosynthesis
      pathways and higher auxin content were found in developing C4 leaves compared
      with developing C3 leaves. The same observation held for maize foliar (C4) and
      husk (C3) leaf primordia. Moreover, auxin content and vein density were increased
      in loss-of-function mutants of Arabidopsis MYC2, a suppressor of auxin
      biosynthesis. Treatment with an auxin biosynthesis inhibitor or an auxin
      transport inhibitor led to much fewer veins in new leaves. Finally, both
      Arabidopsis thaliana auxin efflux transporter pin1 and influx transporter lax2
      mutants showed reduced vein numbers. Thus, development of high leaf vein density
      requires elevated auxin biosynthesis and transport.

PMID- 28761001
TI  - DNA damage tolerance in hematopoietic stem and progenitor cells in mice.
AB  - DNA damage tolerance (DDT) enables bypassing of DNA lesions during replication,
      thereby preventing fork stalling, replication stress, and secondary DNA damage
      related to fork stalling. Three modes of DDT have been documented: translesion
      synthesis (TLS), template switching (TS), and repriming. TLS and TS depend on
      site-specific PCNA K164 monoubiquitination and polyubiquitination, respectively.
      To investigate the role of DDT in maintaining hematopoietic stem cells (HSCs) and
      progenitors, we used PcnaK164R/K164R mice as a unique DDT-defective mouse model.
      Analysis of the composition of HSCs and HSC-derived multipotent progenitors
      (MPPs) revealed a significantly reduced number of HSCs, likely owing to increased
      differentiation of HSCs toward myeloid/erythroid-associated MPP2s. This skewing
      came at the expense of the number of lymphoid-primed MPP4s, which appeared to be
      compensated for by increased MPP4 proliferation. Furthermore, defective DDT
      decreased the numbers of MPP-derived common lymphoid progenitor (CLP), common
      myeloid progenitor (CMP), megakaryocyte-erythroid progenitor (MEP), and
      granulocyte-macrophage progenitor (GMP) cells, accompanied by increased cell
      cycle arrest in CMPs. The HSC and MPP phenotypes are reminiscent of premature
      aging and stressed hematopoiesis, and indeed progressed with age and were
      exacerbated on cisplatin exposure. Bone marrow transplantations revealed a strong
      cell intrinsic defect of DDT-deficient HSCs in reconstituting lethally irradiated
      mice and a strong competitive disadvantage when cotransplanted with wild-type
      HSCs. These findings indicate a critical role of DDT in maintaining HSCs and
      progenitor cells, and in preventing premature aging.

PMID- 28761002
TI  - Intraflagellar transport velocity is governed by the number of active KIF17 and
      KIF3AB motors and their motility properties under load.
AB  - Homodimeric KIF17 and heterotrimeric KIF3AB are processive, kinesin-2 family
      motors that act jointly to carry out anterograde intraflagellar transport (IFT),
      ferrying cargo along microtubules (MTs) toward the tips of cilia. How IFT trains
      attain speeds that exceed the unloaded rate of the slower, KIF3AB motor remains
      unknown. By characterizing the motility properties of kinesin-2 motors as a
      function of load we find that the increase in KIF3AB velocity, elicited by
      forward loads from KIF17 motors, cannot alone account for the speed of IFT trains
      in vivo. Instead, higher IFT velocities arise from an increased likelihood that
      KIF3AB motors dissociate from the MT, resulting in transport by KIF17 motors
      alone, unencumbered by opposition from KIF3AB. The rate of transport is therefore
      set by an equilibrium between a faster state, where only KIF17 motors move the
      train, and a slower state, where at least one KIF3AB motor on the train remains
      active in transport. The more frequently the faster state is accessed, the higher
      the overall velocity of the IFT train. We conclude that IFT velocity is governed
      by (i) the absolute numbers of each motor type on a given train, (ii) how prone
      KIF3AB is to dissociation from MTs relative to KIF17, and (iii) how prone both
      motors are to dissociation relative to binding MTs.

PMID- 28761003
TI  - Multiple PPR protein interactions are involved in the RNA editing system in
      Arabidopsis mitochondria and plastids.
AB  - Recent identification of several different types of RNA editing factors in plant
      organelles suggests complex RNA editosomes within which each factor has a
      different task. However, the precise protein interactions between the different
      editing factors are still poorly understood. In this paper, we show that the E+
      type pentatricopeptide repeat (PPR) protein SLO2, which lacks a C-terminal
      cytidine deaminase-like DYW domain, interacts in vivo with the DYW-type PPR
      protein DYW2 and the P-type PPR protein NUWA in mitochondria, and that the latter
      enhances the interaction of the former ones. These results may reflect a protein
      scaffold or complex stabilization role of NUWA between E+-type PPR and DYW2
      proteins. Interestingly, DYW2 and NUWA also interact in chloroplasts, and DYW2
      GFP overexpressing lines show broad editing defects in both organelles, with
      predominant specificity for sites edited by E+-type PPR proteins. The latter
      suggests a coordinated regulation of organellar multiple site editing through
      DYW2, which probably provides the deaminase activity to E+ editosomes.

PMID- 28761005
TI  - Conceptual foundations of evolutionary thought.

PMID- 28761004
TI  - Multicenter Observational Study of the Use of Nebulized Hypertonic Saline to
      Treat Children Hospitalized for Bronchiolitis From 2008 to 2014.
AB  - OBJECTIVES: Among children hospitalized for bronchiolitis, we examined temporal
      trends in the use of hypertonic saline (HTS) and the characteristics associated
      with receiving this treatment. METHODS: We conducted a secondary analysis of data
      from 2 large, multicenter prospective cohort studies that included young children
      hospitalized with bronchiolitis during 5 winter seasons (2008-2014). Our outcome
      was receipt of HTS any time during the preadmission visit or hospitalization. For
      comparison with the observed trends in HTS use, we conducted a PubMed literature
      review of studies evaluating HTS use for bronchiolitis. We classified
      publications according to their assessment of HTS efficacy (positive, negative,
      or neutral). RESULTS: Among 2709 hospitalized children, 241 (8.9%) received HTS.
      There was marked variability in HTS use by site (0%-91%), with use more common
      among children admitted to the ICU than those treated on the ward (31% vs 15%).
      Over the study period, administration of HTS increased from 2% during the 2008
      2009 season to 27% during the 2011-2012 season, but then it decreased to 11%
      during the 2013-2014 season. Before 2010, the number of PubMed HTS publications
      ranged from 0 to 3 articles per year, with all classified as either positive or
      neutral. The number of positive publications increased in 2010 (n = 5), whereas
      negative publications peaked in 2014 (n = 4). CONCLUSIONS: Use of HTS in children
      hospitalized with bronchiolitis increased during the 2008 to 2012 winter seasons
      and then declined. These findings paralleled trends in the HTS literature, with
      positive articles encouraging HTS use in early years followed by a growing number
      of neutral and negative articles after 2012.

PMID- 28761006
TI  - Unpacking the species conundrum: philosophy, practice and a way forward.
AB  - The history of ecology and evolutionary biology is rife with attempts to define
      and delimit species. However, there has been confusion between concepts and
      criteria, which has led to discussion, debate, and conflict, eventually leading
      to lack of consistency in delimitation. Here, we provide a broad review of
      species concepts, a clarification of category versus concept, an account of the
      general lineage concept (GLC), and finally a way forward for species discovery
      and delimitation. Historically, species were considered as varieties bound
      together by reproduction. After over 200 years of uncertainty, Mayr attempted to
      bring coherence to the definition of species through the biological species
      concept (BSC). This has, however, received much criticism, and the last half
      century has spawned at least 20 other concepts. A central philosophical problem
      is that concepts treat species as 'individuals' while the criteria for
      categorization treats them as 'classes'. While not getting away from this problem
      entirely, the GLC attempts to provide a framework where lineage divergence is
      influenced by a number of different factors (and correlated to different traits)
      which relate to the different species concepts. We also introduce an 'inclusive'
      probabilistic approach for understanding and delimiting species. Finally, we
      provide aWallacean (geography related) approach to the Linnaean problem of
      identifying and delimiting species, particularly for cases of allopatric
      divergence, and map this to the GLC. Going one step further, we take a
      morphometric terrain approach to visualizing and understanding differences
      between lineages. In summary, we argue that while generalized frameworks may work
      well for concepts of what species are, plurality and 'inclusive' probabilistic
      approaches may work best for delimitation.

PMID- 28761007
TI  - Complexity: the organizing principle at the interface of biological (dis)order.
AB  - The term complexity means several things to biologists.When qualifying
      morphological phenotype, on the one hand, it is used to signify the sheer
      complicatedness of living systems, especially as a result of the multicomponent
      aspect of biological form. On the other hand, it has been used to represent the
      intricate nature of the connections between constituents that make up form: a
      more process-based explanation. In the context of evolutionary arguments,
      complexity has been defined, in a quantifiable fashion, as the amount of
      information, an informatic template such as a sequence of nucleotides or amino
      acids stores about its environment. In this perspective, we begin with a brief
      review of the history of complexity theory. We then introduce a developmental and
      an evolutionary understanding of what it means for biological systems to be
      complex.We propose that the complexity of living systems can be understood
      through two interdependent structural properties: multiscalarity of
      interconstituent mechanisms and excitability of the biological materials. The
      answer to whether a system becomes more or less complex over time depends on the
      potential for its constituents to interact in novel ways and combinations to give
      rise to new structures and functions, as well as on the evolution of excitable
      properties that would facilitate the exploration of interconstituent organization
      in the context of their microenvironments and macroenvironments.

PMID- 28761009
TI  - Ascus dysgenesis in hybrid crosses of Neurospora and Sordaria (Sordariaceae).
AB  - When two lineages derived from a common ancestor become reproductively isolated
      (e.g. Neurospora crassa and N. tetrasperma), genes that have undergone mutation
      and adaptive evolution in one lineage can potentially become dysfunctional when
      transferred into the other, since other genes have undergone mutation and
      evolution in the second lineage, and the derived alleles were never 'tested'
      together before hybrid formation. Bateson (1909), Dobzhansky (1936), and Muller
      (1942) recognized that incompatibility between the derived alleles could
      potentially make the hybrid lethal, sterile, or display some other detriment.
      Alternatively, the detrimental effects seen in crosses with the hybrids may
      result from the silencing of ascus-development genes by meiotic silencing by
      unpaired DNA (MSUD). Aberrant transcripts from genes improperly paired in meiosis
      are processed into single-stranded MSUD-associated small interfering RNA
      (masiRNA), which is used to degrade complementary mRNA. Recently, backcrosses of
      N. crassa / N. tetrasperma hybrid translocation strains with wild-type N.
      tetrasperma were found to elicit novel ascus dysgenesis phenotypes. One was a
      transmission ratio distortion that apparently disfavoured the homokaryotic
      ascospores formed following alternate segregation. Another was the production of
      heterokaryotic ascospores in eight-spored asci. Lewis (1969) also had reported
      sighting rare eight-spored asci with heterokaryotic ascospores in interspecific
      crosses in Sordaria, a related genus. Ordinarily, in both Neurospora and
      Sordaria, the ascospores are partitioned at the eight-nucleus stage, and
      ascospores in eight-spored asci are initially uninucleate. Evidently, in hybrid
      crosses of the family Sordariaceae, ascospore partitioning can be delayed until
      after one or more mitoses following the postmeiotic mitosis.

PMID- 28761008
TI  - Epigenetic inheritance, prions and evolution.
AB  - The field of epigenetics has grown explosively in the past two decades or so. As
      currently defined, epigenetics deals with heritable, metastable and usually
      reversible changes that do not involve alterations in DNA sequence, but alter the
      way that information encoded inDNAis utilized.The bulk of current research in
      epigenetics concerns itself with mitotically inherited epigenetic processes
      underlying development or responses to environmental cues (as well as the role of
      mis-regulation or dys-regulation of such processes in disease and ageing), i.e.,
      epigenetic changes occurring within individuals. However, a steadily growing body
      of evidence indicates that epigenetic changes may also sometimes be transmitted
      from parents to progeny, meiotically in sexually reproducing organisms or
      mitotically in asexually reproducing ones. Such transgenerational epigenetic
      inheritance (TEI) raises obvious questions about a possible evolutionary role for
      epigenetic 'Lamarckian' mechanisms in evolution, particularly when epigenetic
      modifications are induced by environmental cues. In this review I attempt a brief
      overview of the periodically reviewed and debated 'classical' TEI phenomena and
      their possible implications for evolution. The review then focusses on a less
      discussed, unique kind of protein-only epigenetic inheritance mediated by prions.
      Much remains to be learnt about the mechanisms, persistence and effects of TEI.
      The jury is still out on their evolutionary significance and how these phenomena
      should be incorporated into evolutionary theory, but the growing weight of
      evidence indicates that likely evolutionary roles for these processes need to be
      seriously explored.

PMID- 28761011
TI  - Co-niche construction between hosts and symbionts: ideas and evidence.
AB  - Symbiosis is a process that can generate evolutionary novelties and can extend
      the phenotypic niche space of organisms. Symbionts can act together with their
      hosts to co-construct host organs, within which symbionts are housed. Once
      established within hosts, symbionts can also influence various aspects of host
      phenotype, such as resource acquisition, protection from predation by acquisition
      of toxicity, as well as behaviour. Once symbiosis is established, its fidelity
      between generations must be ensured. Hosts evolve various mechanisms to screen
      unwanted symbionts and to facilitate faithful transmission of mutualistic
      partners between generations. Microbes are the most important symbionts that have
      influenced plant and animal phenotypes; multicellular organisms engage in
      developmental symbioses with microbes at many stages in ontogeny. The co
      construction of niches may result in composite organisms that are physically
      nested within each other. While it has been advocated that these composite
      organisms need new evolutionary theories and perspectives to describe their
      properties and evolutionary trajectories, it appears that standard evolutionary
      theories are adequate to explore selection pressures on their composite or
      individual traits. Recent advances in our understanding of composite organisms
      open up many important questions regarding the stability and transmission of
      these units.

PMID- 28761012
TI  - Niche construction in evolutionary theory: the construction of an academic niche?

PMID- 28761013
TI  - Why Gupta et al.'s critique of niche construction theory is off target.
AB  - Gupta et al., in their article in this issue ('Niche construction in evolutionary
      theory: the construction of an academic niche?'. doi:10.1007/s12041-017-0787-6),
      lament 'serious problems with the way science is being done' and suggest that
      'niche construction theory exemplifies this state of affairs.' However, their
      aggressively confrontational but superficial critique of niche construction
      theory (NCT) only contributes to these problems by attacking claims that NCT does
      not make. This is unfortunate, as their poor scholarship has done a disservice to
      the evolutionary biology community through propagating misinformation.We correct
      Gupta et al.'s misunderstandings, stressing that NCT does not suggest that the
      fact that organisms engage in niche construction is neglected, nor does it make
      strong claims on the basis of its formal theory. Moreover, the treatment of niche
      construction as an evolutionary process has been highly productive, and is both
      theoretically and empirically well-validated.We end by reflecting on the
      potentially deleterious implications of their publication for evolutionary
      science.

PMID- 28761010
TI  - The placental gateway of maternal transgenerational epigenetic inheritance.
AB  - While much of our understanding of genetic inheritance is based on the genome of
      the organism, it is becoming clear that there is an ample amount of epigenetic
      inheritance, which though reversible, escapes erasing process during
      gametogenesis and goes on to the next generation. Several examples of
      transgenerational inheritance of epigenetic features with potential impact on
      embryonic development and subsequent adult life have come to light. In placental
      mammals, the placenta is an additional route for epigenetic information flow.
      This information does not go through any meiotic reprogramming and is, therefore,
      likely to have a more profound influence on the organism. This also has the
      implication of providing epigenetic instructions for several months, which is
      clearly a maternal advantage. Although less well-known, there is also an impact
      of the embryo in emitting genetic information to the maternal system that remains
      well beyond the completion of the pregnancy. In this review, we discuss several
      factors in the context of the evolution of this mammal-specific phenomenon,
      including genomic imprinting, micromosaicism, and assisted reproduction. We also
      highlight how this kind of inheritance might require attention in the modern
      lifestyle within the larger context of the evolutionary process.

PMID- 28761014
TI  - Feldman et al. do protest too much, we think.

PMID- 28761015
TI  - The evolution of culture (or the lack thereof): mapping the conceptual space.
AB  - This short essay is based on a lecture that I gave at short notice on a subject
      in which I am by no means an expert. The combination of lack of expertise and
      time for preparation, created an unexpectedly unique opportunity for thinking
      outside the box. I decided not to try to read up (as there was no time in any
      case) but instead to organize the little that I already knew about cultural
      evolution in a systematic schema-I attempted to create a scaffolding, on which I
      could hang everything I knew about cultural evolution, and hopefully, everything
      I might ever discover about cultural evolution in the future. I considered three
      dimensions of the study of cultural evolution, namely (i) the phenomenon of
      cultural evolution, (ii) production of knowledge in the field of cultural
      evolution, and (iii) the consequences or applications of an understanding of the
      evolution of culture.

PMID- 28761016
TI  - The evolution of religious belief in humans: a brief review with a focus on
      cognition.
AB  - Religion has been a widely present feature of human beings. This review explores
      developments in the evolutionary cognitive psychology of religion and provides
      critical evaluation of the different theoretical positions. Generally scholars
      have either believed religion is adaptive, a by-product of adaptive psychological
      features or maladaptive and varying amounts of empirical evidence supports each
      position. The adaptive position has generated the costly signalling theory of
      religious ritual and the group selection theory. The by-product position has
      identified psychologicalmachinery that has been co-opted by religion. The
      maladaptive position has generated the meme theory of religion. The review
      concludes that the by-product camp enjoys the most support in the scientific
      community and suggests ways forward for an evolutionarily significant study of
      religion.

PMID- 28761017
TI  - Social behavioural epistemology and the scientific community.
AB  - The progress of science is influenced substantially by social behaviour of and
      social interactions within the scientific community. Similar to innovations in
      primate groups, the social acceptance of an innovation depends not only upon the
      relevance of the innovation but also on the social dominance and connectedness of
      the innovator. There are a number of parallels between many well-known phenomena
      in behavioural evolution and various behavioural traits observed in the
      scientific community. It would be useful, therefore, to use principles of
      behavioural evolution as hypotheses to study the social behaviour of the
      scientific community. I argue in this paper that a systematic study of social
      behavioural epistemology is likely to boost the progress of science by addressing
      several prevalent biases and other problems in scientific communication and by
      facilitating appropriate acceptance/rejection of novel concepts.

PMID- 28761018
TI  - Dynamic thiol/disulphide homeostasis as a novel indicator of oxidative stress in
      obese children and its relationship with inflammatory-cardiovascular markers.
AB  - OBJECTIVE: Childhood obesity is an important cause of cardiovascular risk with
      chronic inflammation. Oxidative stress may contribute to the pathogenesis of
      obesity-related cardiovascular pathologies. We aimed to evaluate thiol/disulphide
      homeostasis as a novel and sensitive marker of oxidative stress and to evaluate
      its relationship with some inflammatory and cardiovascular markers in obese
      children. METHODS: In this case-controlled study, 65 children with exogenous
      obesity and 64 healthy children, as a control group, were included. In both
      groups, thiol/disulphide homeostasis parameters and inflammatory (white blood
      cells, platelets, mean corpuscular volume, neutrophil/lymphocyte ratio, and high
      sensitivity C-reactive protein) and cardiovascular (epicardial adipose tissue
      thickness and left ventricular mass index) markers were studied. Correlation
      analyses of thiol/disulphide homeostasis parameters with body mass index standard
      deviation scores (BMI SDS) and inflammatory and cardiovascular markers were
      performed. Receiver-operating characteristic analysis was performed to determine
      the sensitivity, specificity, and optimal cut-off values of thiol/disulphide
      homeostasis parameters. RESULTS: Native thiol, total thiol, and native
      thiol/total thiol ratios (antioxidant parameters) were lower (p<0.05) and
      disulphide/native thiol and disulphide/total thiol ratios (oxidant parameters)
      were higher in the obese group than in the control group (p<0.01). A positive
      correlation of oxidant parameters with BMI SDS and inflammatory markers was
      found. However, a negative correlation of antioxidant parameters with BMI SDS and
      inflammatory markers was found. The specificities of disulphide/native thiol and
      disulphide/total thiol ratios were higher in the obese group. CONCLUSION: The
      impairment in thiol/disulphide homeostasis, which is indicative of oxidative
      stress, is associated with inflammation in obesity. In addition, cardiovascular
      involvement may also contribute to this impairment.

PMID- 28761020
TI  - Changes in neutrophil-to-lymphocyte ratios in postcardiac arrest patients treated
      with targeted temperature management.
AB  - OBJECTIVE: The prognostic value of changes in neutrophil-to-lymphocyte ratios
      (NLR) in cardiac arrest survivors receiving targeted temperature management (TTM)
      is unknown. The current study investigated NLR in postcardiac arrest (PCA)
      patients undergoing TTM. METHODS: This retrospective single-center study included
      95 patients (59 males, age: 55.0+/-17.0 years) with in-hospital and out-of
      hospital cardiac arrests who underwent TTM for PCA syndrome within 6 h of cardiac
      arrest. Hypothermia was maintained for 24 h at a target temperature of 33 degrees
      C. NLR was calculated as the absolute neutrophil count divided by the absolute
      lymphocyte count. RESULTS: Of the 95 patients, 59 (62%) died during hospital
      stay. Fewer vasopressors were used in patients who survived. Out-of-hospital
      cardiac arrest was more frequent in decedents (p=0.005). Length of stay in the
      hospital and intensive care unit were significantly longer in patients who
      survived (p=0.0001 and p=0.001, respectively). NLR on admission and during
      rewarming did not differ between survivors and decedents. NLR during cooling was
      significantly higher in decedents (p=0.014). Delta NLR cut-off of 13.5 best
      separated survivors and decedents (AUC=0.68, 95% CI: 0.57-0.79, p=0.003 with a
      sensitivity and specificity of 64% and 67%, respectively). In multivariate
      logistic regression analysis, larger increase in NLR was significantly associated
      with decreased survival (OR: 0.96, 95% CI: 0.94-0.99, p=0.008). CONCLUSION:
      Changes in NLR are an independent determinant of survival in patients with return
      of spontaneous circulation PCA treated with TTM. An NLR change can be used to
      predict survival in these patients.

PMID- 28761019
TI  - Effects of trimetazidine on mitochondrial respiratory function, biosynthesis, and
      fission/fusion in rats with acute myocardial ischemia.
AB  - OBJECTIVE: Myocardial ischemia affects mitochondrial functions, leading to ionic
      imbalance and susceptibility to ventricular fibrillation. Trimetazidine, a
      metabolic agent, is clinically used in anti-anginal therapy. METHODS: In this
      study, the rats were orally treated by gavage with trimetazidine 10 mg/kg/d for 7
      days, and the effects of trimetazidine on mitochondrial respiratory function,
      biosynthesis, and fission/fusion in rats with acute myocardial ischemia were
      evaluated. RESULTS: It has been suggested that acute myocardial ischemia leads to
      a damage to mitochondrial functions. However, compared with ischemia group
      without trimetazidine administration, a significant reduction in the infarct size
      was observed in trimetazidine-treated ischemia group (31.24+/-3.02% vs. 52.87+/
      4.89%). Trimetazidine preserved the mitochondrial structure and improved
      respiratory control ratio and complex I activity. Furthermore, trimetazidine
      improved mitochondrial biosynthesis and fission/fusion, as demonstrated by the
      promotion of peroxisome proliferator-activated receptor gamma (PPARgamma) co
      activator 1alpha (PGC-1alpha), mitofusins 1 (Mfn1), dynamin-related protein 1
      (Drp1), and optic atrophy 1 (Opa1) expressions in rats with acute myocardial
      ischemia. CONCLUSION: Taken together, it was suggested that in this rat model of
      myocardial ischemia, trimetazidine demonstrated cardioprotective effects
      attributing to the preservation of mitochondrial respiratory function,
      biosynthesis, and fission/fusion and, thus, could be considered as an agent for
      cardioprotection.

PMID- 28761021
TI  - Prognostic role of soluble suppression of tumorigenicity-2 on cardiovascular
      mortality in outpatients with heart failure.
AB  - OBJECTIVE: Soluble suppression of tumorigenicity-2 (sST2), a member of the
      interleukin 1 receptor family, is increased in mechanical stress conditions and
      is produced by cardiomyocytes and cardiac fibroblasts. Elevated sST2 level is
      associated with the prognosis of acute coronary syndrome, pulmonary arterial
      hypertension, and acute and chronic heart failure (HF). In this study, we aimed
      to investigate the relationship between sST2 levels and cardiovascular mortality
      in outpatients with HF. METHODS: This study used a prospective observational
      cohort design. A total of 130 consecutive outpatients with HF were prospectively
      evaluated. Clinical characteristics, laboratory results, cardiovascular risk
      factors, comorbidities, and medication use were recorded. The patients were
      followed up for a mean period of 12+/-4 months for the development of
      cardiovascular death. They were classified into two groups: those who survived
      and those who died. RESULTS: Mean age of patients was 67+/-11 years (69% males).
      After follow-up, 23 of 130 patients (18%) experienced cardiovascular death. sST2
      levels were higher among those who died compared with among those who survived
      [51 (21-162) vs. 27 (9-198) ng/mL, p<0.001]. Optimal cut-off sST2 level to
      predict cardiovascular mortality was found to be >30 ng/mL with a sensitivity of
      87% and a specificity of 67% (AUC =0.808, 95% CI=0.730 to 0.872). sST2 levels
      were negatively correlated with left ventricular ejection fraction and
      triglyceride, total cholesterol, LDL cholesterol, and hemoglobin levels and were
      positively correlated with left atrium size and the presence of right ventricular
      dilatation. In multiple Cox regression analysis, sST2 level of >30 ng/mL
      (HR=6.756, p=0.002, 95% CI=1.983-23.018), hemoglobin level (HR=0.705, p<0.001,
      95% CI=0.587-0.847), age (HR=1.050, p=0.013, 95% CI=1.010-1.091), and HDL
      cholesterol level (HR=0.936, p=0.010, 95% CI=0.889-0.984) remained to be
      associated with an increased risk of mortality. CONCLUSION: sST2 measurement
      could help risk stratification in outpatients with HF. Moreover, this is the
      first study describing the impact of sST2 protein in Turkish patients with HF.

PMID- 28761022
TI  - Vagal denervation in atrial fibrillation ablation: A comprehensive review.
AB  - Although pulmonary vein isolation is accepted as an established interventional
      treatment in paroxysmal atrial fibrillation (AF), alternative modalities are
      being investigated because of the high recurrence rates of nonparoxysmal forms.
      One of the alternative ablation approaches is ablation or modification of vagal
      ganglionated plexi (VGP). The technique has not only been used in vagally
      mediated AF but also investigated in paroxysmal and nonparoxysmal AF. Clinical
      studies demonstrate significant discrepancy related with detection of VGP sites
      or ablation targets and definition of procedurel end-points, so far. In this
      review, we aimed to discuss the current data on the role of VGP in the
      pathogenesis of AF and potential therapeutic implications of ablation of these
      ganglia.

PMID- 28761023
TI  - A comparison of the in vivo neoendothelialization and wound healing processes of
      three atrial septal defect occluders used during childhood in a nonrandomized
      prospective trial.
AB  - OBJECTIVE: We prospectively investigated the neoendothelialization of
      transcatheter secundum atrial septal defect (ASD) closure in children receiving
      one of three different occluders. METHODS: Transcatheter ASD closure was
      performed for 44 children. The patients were divided into three groups: group I:
      Amplatzer, group II: Lifetech CeraFlex, and group III: Occlutech Figulla Flex II
      septal occluder. The data were prospectively analyzed. Markers of the three
      phases of wound healing were studied in all patients before and on the 1st and
      10th days and 1st month post intervention. RESULTS: The mean age of children was
      7.08+/-3.51 years, and the mean weight was 26.07+/-15.07 kg. The mean ASD
      diameter was 12.65+/-3.50 mm. Groups I, II, and III comprised 34.1%, 31.8%, and
      34.1% patients, respectively. No significant differences were observed between
      the groups regarding patient number, age, defect size, device diameter, or total
      septum/device ratio (p>0.05). Inflammatory and proliferative phase marker levels
      increased following the procedure (p<0.05). However, scar formation markers did
      not change after 1 month. No significant differences in neoendothelializaton were
      observed among the different occluders (p>0.05). CONCLUSION: All three devices
      were composed of nitinol with different surface coating techniques. Although the
      different manufacturing features were claimed to facilitate of
      neoendothelialization, no differences were observed among the three devices 1
      month following the procedure.

PMID- 28761024
TI  - Hepatitis B and C virus prevalence in couples attending an in vitro fertilization
      clinic in a tertiary care hospital in Saudi Arabia: comparison with ten years
      earlier.
AB  - BACKGROUND: Viral hepatitis B (HBV) and C (HCV) are a major public health problem
      in Saudi Arabia. Recent data has indicated a major reduction in viral hepatitis
      prevalence in Saudi population. However, there is limited data for infertile
      Saudi couples. OBJECTIVES: To determine the prevalence of HCV and HBV attending
      an in vitro fertilization (IVF) clinic in Saudi Arabia between 2012 and 2015 to
      compare with the prevalence 10 years earlier in the same center. DESIGN:
      Retrospective prevalence study. SETTING: Tertiary care center in Riyadh. PATIENTS
      AND METHODS: Data on the prevalence of HBV and HCV was collected on all couples
      seen at the IVF unit between 2002-2005 and 2012-2015. MAIN OUTCOME MEASURE(S):
      Prevalence of HBV and HCV. RESULTS: In 4442 patients during 2002-2005 and 5747
      patients during 2012-2015, the prevalence of HBV was significantly less in 2012
      2015 compared with 2002-2005 (1.67% [97 patients] vs 4.7% [210 patients], P <
      .0001), respectively, but HCV prevalence was similar for the two periods (0.7%
      for both periods) (P=.887). The hepatitis B seroprevalence rate was higher in
      males compared to females during 2002-2005 (6.3% vs 3.1%) (P < .0001) and 2012
      2015 (2.4% vs 1.1% ) (P < .0001), respectively. CONCLUSION: The significant drop
      in HBV prevalence was most likely due to the introduction of the vaccination
      program in 1989, while reasons for HCV prevalence remaining unchanged are
      unclear. LIMITATION: No data on confounding factors that may have affected the
      prevalence.

PMID- 28761025
TI  - Eleven-year review of data on Pap smears in Saudi Arabia: We need more focus on
      glandular abnormalities!
AB  - BACKGROUND: We reviewed data from Saudi Arabia on epithelial cell abnormalities
      (ECA) detected by Pap smear after noticing a slight increase in the incidence of
      cervical glandular abnormalities in our regional laboratory in recent years.
      OBJECTIVE: Clarify data on adenocarcinoma (ADCA) on Pap smears in Saudi Arabia.
      DESIGN: Descriptive, retrospective study. SETTINGS: Regional laboratory, Riyadh.
      PATIENTS AND METHODS: We reviewed all Pap smears of adult females between 2006
      and 2016 and compared our data with previously published results from Saudi
      Arabia. MAIN OUTCOME MEASURE(S): Descriptive data on ECAs. RESULTS: Among 19759
      cases, atypical squamous cell of undetermined significance (ASC-US) was the most
      prevalent ECA (1.16%). ADCA occurred more than squamous cell carcinoma (SCC). In
      a comparison of published data before 2014 and after 2014 (including ours), there
      was a significant rise in ADCA (28 vs 48 cases; P=.004) with a significant drop
      in SCC, high-grade squamous intraepithelial lesions (HSIL) and low-grade squamous
      intraepithelial lesions (LSIL) (P < .0001, .004, and < .0001, respectively).
      CONCLUSION: We recommend that pathologists and cytotechnologists be vigilant in
      screening Pap smears in our population, particularly for glandular abnormalities.
      We also recommend use of Pap smears in the initial workup of women with suspected
      gynecological abnormalities, regardless of evolutions in HPV testing.
      LIMITATIONS: The pooling of data instead of analyzing by study year.

PMID- 28761026
TI  - Utilization and adherence to guideline-recommended lipid-lowering therapy at an
      academic medical center.
AB  - BACKGROUND: Clinical guidelines for managing blood cholesterol were updated in
      November 2013. OBJECTIVE: To evaluate the adherence to the 2013 American College
      of Cardiology/American Heart Association (ACC/AHA) guideline recommendations for
      statin therapy in the treatment of elevated blood cholesterol in high-risk
      patients. DESIGN: A single-center, retrospective, observational study. SETTING: A
      tertiary care academic medical center in Riyadh, Saudi Arabia. PATIENTS:
      Consecutive adult patients discharged with a prescription for any of the statin
      medications group between 1 June 2015 and 31 December 2015. MAIN OUTCOME
      MEASURE(S): Adherence to the 2013 ACC/AHA guidelines for management of
      cholesterol by statin therapy in high-risk patients. RESULTS: Of 1094 patients,
      753 (68.8%) met the inclusion criteria of the study. Of these 753 patients, 53.5%
      had atherosclerotic cardiovascular diseases; 29.2% had diabetes; 0.9% had an LDL
      C level > 190 mg/dL; 10.8% had an estimated 10-year risk > 7.5%; and 4.9% had no
      risk. Two hundred and eight (27.6%) patients received statin therapy at an
      inappropriate intensity according to their risk group based on the guideline; 126
      (16.7%) received less than the ideal intensity. CONCLUSION: Approximately one
      third of patients received statin therapy at an inappropriate intensity according
      to the guideline recommendation. Wide application of the 2013 ACC/AHA cholesterol
      guidelines in our practice would optimize the utilization of statin therapy at
      the ideal intensity in high-risk patients. LIMITATION: Drug-drug interactions and
      intolerance to statin therapy were not considered when we evaluated adherence
      among high-risk patients.

PMID- 28761027
TI  - Five-year epidemiological trends for chemical poisoning in Jeddah, Saudi Arabia.
AB  - BACKGROUND: Poisoning is a significant global public health challenge in terms of
      morbidity and mortality. We conducted this study because of the lack of large
      population-based studies on chemical poisoning in Saudi Arabia. OBJECTIVE:
      Describe epidemiological trends, associated factors, and outcomes of chemical
      poisoning cases reported to the Jeddah Health Affairs Directorate, Saudi Arabia.
      DESIGN: Descriptive, retrospective medical record review. SETTING: Population
      database for the Jeddah Governorate. METHODS: For chemical poisoning cases
      reported from January 2011 to December 2015, data was collection using a
      standardized, validated data collection sheet. Data was collected on personal
      characteristics, type of chemical poisoning and outcome. MAIN OUTCOME MEASURE(S):
      Descriptive epidemiological data and statistical comparisons. RESULTS: For 994
      chemical poisoning cases, an increasing trend was observed from 2011 to 2013
      followed by some reduction during 2014 and 2015. The highest percentage of cases
      occurred during July followed by March for the cumulative total cases by month
      for all years. More than half of the cases involved males (55%), and children
      aged less than 5 years (56.6%). About three-fourths of the cases occurred
      accidentally and through ingestion. The most common poisonous agents were
      detergents (36.0%). Poisoning with addictive drugs occurred in 13 cases (1.3%).
      Only 1.1% of cases received a poisoning specific antidote, and the same
      percentage died because of poisoning. Gender, age, nationality, the route and the
      circumstances of the exposure were significantly associated with the type of
      poisoning (P < .001). CONCLUSION: Most of chemical poisoning cases were
      accidental, occurred during summer, were caused by detergents, affected children
      < 5 years of age, and occurred via ingestion. Educational programs are needed to
      raise public awareness about poisoning, and to minimize the access of children to
      poisonous agents, especially detergents. Such measures could contribute toward a
      further reduction of the chemical poisoning burden. LIMITATIONS: Some key
      statistics not reported. Information bias may have affected results.

PMID- 28761028
TI  - Variation in access to pediatric surgical care among coexisting public and
      private providers: inguinal hernia as a model.
AB  - BACKGROUND: Faced with growing healthcare demand, the Saudi government is
      increasingly relying on privatization as a tool to improve patient access to
      care. Variation in children's access to surgical care between public (PB) and
      private providers (PV) has not been previously analyzed. OBJECTIVES: To compare
      access to pediatric surgical services between two coexisting PB and PV. DESIGN:
      Retrospective comparative study. SETTINGS: A major teaching hospital and the
      largest PV group in Saudi Arabia. PATIENTS AND METHODS: The outcomes for children
      who underwent inguinal herniotomy (IH) between May 2010 and December 2014 at both
      providers were with IH serving as the model. Data collected included patient
      demographics, insurance coverage, referral pattern and access parameters
      including time-to-surgery (TTS), surgery wait time (SWT) and duration of symptoms
      (DOS). MAIN OUTCOME MEASURE(S): TTS, SWT and DOS. RESULTS: Of 574 IH cases, 56
      cases of in-hospital referrals were excluded leaving 290 PB and 228 PV cases. PV
      patients were younger (12.0 vs 16.4 months, P=.043) and more likely to be male
      (81.6% vs 72.8%, P=.019), expatriates (18% vs 3.4%, P < .001) and insured (47.4%
      vs 0%, P < .001). The emergency department was more frequently the source for PB
      referrals (35.2% vs 12.7%, P < .001) while most PV patients were self-referred
      (72.8% vs 16.7%, P < .001). Access parameters were remarkably better at PV: TTS
      (21 vs 66 days, P < .001), SWT (4 vs 31 days, P < .001) and DOS (33 vs 114 days,
      P < .001). CONCLUSION: When coexisting, PV offers significantly better access to
      pediatric surgical services compared to PB. Diverting public funds to expand
      children's access to PV can be a valid choice to improve access to care in case
      when outcomes with the two providers are similar. LIMITATIONS: Although it is the
      first and largest comparison in the pediatric population, the sample may not
      represent the whole population since it is confined to a single selected surgical
      condition.

PMID- 28761029
TI  - Isometric muscle fatigue of the paravertebral and upper extremity muscles after
      whiplash injury.
AB  - BACKGROUND: Whiplash-associated disorders (WAD) result from injury of neck
      structures that most often occur during traffic accidents as a result of rapid
      acceleration-deceleration. The dominant symptoms manifest in the musculoskeletal
      system and include increased fatigue. Because of the frequency of whiplash
      injuries, a simple, cheap and useful diagnostic tool is needed to differentiate
      whiplash injury from healthy patients or those faking symptoms. OBJECTIVES: To
      determine muscle fatigue in patients with whiplash injury in six body positions.
      DESIGN: Analytical cross-sectional study. SETTING: Emergency center, university
      hospital. PATIENTS AND METHODS: We studied patients with whiplash injury from
      vehicular traffic accidents who presented to the emergency center within 6 hours
      of sustaining the injury. We determined whiplash injury grade according to the
      Quebec Task Force (QTF) classification and measured isometric muscle endurance in
      six different body positions. Control subjects for each patient were matched by
      age, gender and anthropomorphic characteristics. Cut-off values were determined
      to distinguish patients with whiplash injury from controls and for determination
      of injury grade . MAIN OUTCOME MEASURE(S): QTF grade, time to muscle fatigue in
      seconds. RESULTS: From September 2013 to September 2016, we enrolled 75 patients
      with whiplash injury and 75 matching control subjects. In all six positions, the
      patients with whiplash injury felt muscle fatigue faster than equivalent controls
      (P < .05) and the time to onset of muscle fatigue decreased with increasing
      injury grades in all six positions. Assignment to the patient or control group
      and to injury grade could be predicted with more than 90% accuracy on the basis
      of time to muscle fatigue. The most efficient position was the highest injury
      grade, by which 99.9% of the patients were accurately categorized. Isometric
      muscle endurance correlated with whiplash injury grade in all six positions (P <
      .01). CONCLUSION: Under clinical conditions, muscle endurance and the appearance
      of isometric muscle fatigue during testing can be a useful indicator of whiplash
      injury and grade. LIMITATIONS: The size of the sample was small. An objective
      parameter such as electromyography is needed to confirm isometric muscle fatigue.

PMID- 28761030
TI  - Comparison of the Trendelenburg position versus upper-limb tourniquet on internal
      jugular vein diameter.
AB  - BACKGROUND: Central venous cannulation is a necessary invasive procedure for
      fluid management, haemodynamic monitoring and vasoactive drug therapy. The right
      internal jugular vein (RIJV) is the preferred site. Enlargement of the jugular
      vein area facilitates catheterization and reduces complication rates. Common
      methods to enlarge the RIJV cross-sectional area are the Trendelenburg position
      and the Valsalva maneuver. OBJECTIVE: Compare the Trendelenburg position with
      upper-extremity venous return blockage using the tourniquet technique. DESIGN:
      Prospective clinical study. SETTING: University hospital. SUBJECTS AND METHODS:
      Healthy adult volunteers (American Society of Anesthesiologists class I) aged 18
      45 years were included in the study. The first measurement was made when the
      volunteers were in the supine position. The RIJV diameter and cross-sectional
      area were measured from the apex of the triangle formed by the clavicle and the
      two ends of the sternocleidomastoid muscle, which is used for the conventional
      approach. The second measurement was performed in a 20 degrees  Trendelenburg
      position. After the drainage of the veins using an Esbach bandage both arms were
      cuffed. The third measurement was made when tourniquets were inflated. MAIN
      OUTCOME MEASURE(S): Hemodynamic measurements and RIJV dimensions. RESULTS: In 65
      volunteers the diameter and cross-sectional area of the RIJV were significantly
      widened in both Trendelenburg and tourniquet measurements compared with the
      supine position (P < .001 for both measures). Measurements using the upper
      extremity tourniquet were significantly larger than Trendelenburg measurements
      (P=.002 and < .001 for cross-sectional area and diameter, respectively).
      CONCLUSION: Channelling of the upper-extremity venous return to the jugular vein
      was significantly superior when compared with the Trendelenburg position and the
      supine position. LIMITATIONS: No catheterization and study limited to healthy
      volunteers.

PMID- 28761031
TI  - Indications for enucleation and evisceration in a tertiary eye hospital in Riyadh
      over a 10-year period.
AB  - BACKGROUND: Enucleation and evisceration are eye removal procedures considered as
      palliative treatment when all other therapeutic options are exhausted. OBJECTIVE:
      Describe the causes and histopathological findings leading to
      enucleation/evisceration, and correlate the clinical findings with the
      histopathological findings. DESIGN: Retrospective, descriptive study. SETTINGS:
      Tertiary care hospital, Riyadh, Saudi Arabia. PATIENTS AND METHODS: The medical
      records of patients who underwent enucleation or evisceration from February 2005
      to May 2015 were reviewed. Patients were classified into two categories based on
      indications of surgery: traumatic and nontraumatic. Causes of ocular injury in
      the traumatic group were documented, and the histopathological findings were
      reviewed for the nontraumatic cases. MAIN OUTCOME MEASURE(S): Number of
      enucleation and evisceration surgeries and their causes and histopathological
      findings. RESULTS: One hundred ten patients underwent evisceration (n=69, 63%)
      and enucleation (n=41, 37%). Causes were traumatic in 38 (35%) and nontraumatic
      in 72 (65%). The median age was 50 years and there were 64 men and 46 women.
      Postoperative endophthalmitis was the most common indication for surgery (n=24,
      21.8%), followed by painful blind eye (n=22, 20%). Ocular trauma was more
      predominant in men (n=29, 76%) than in women (n=9, 24%), and the leading
      mechanism of trauma was metallic nail injuries (n=6, 15.8%). In the nontraumatic
      group, endophthalmitis was the most common histopathological finding (n=25,
      34.7%). CONCLUSIONS: The majority of the eye enucleation/evisceration surgeries
      were due to nontraumatic causes, especially postoperative infections. However,
      severe eye trauma was still a main indication for this destructive procedure.
      Guidelines are needed to decrease the incidence/severity of work-related eye
      injuries and to detect and manage eye infections earlier and more promptly.
      LIMITATIONS: Retrospective study, in one hospital in one area; therefore, results
      cannot be generalized.

PMID- 28761032
TI  - Influence of knowledge and beliefs on consumption of performance enhancing agents
      in north-western Saudi Arabia.
AB  - BACKGROUND: Consumption of performance enhancing agents (PEAs) has a wide range
      of negative health consequences, but knowledge of these consequences among gym
      users of PEAs in Saudi Arabia is not well understood. OBJECTIVES: Identify the
      knowledge, awareness, beliefs and attitudes of gym users about negative health
      consequences of using PEAs, and the relationship between these factors and use of
      these agents. DESIGN: Cross-sectional study. SETTING: Five gyms in Madinah city,
      Saudi Arabia. SUBJECTS AND METHODS: Convenience sampling was used to recruit gym
      users. An electronic self-administered questionnaire was used to collect data.
      MAIN OUTCOME MEASURE(S): Level of knowledge about the negative health
      consequences of PEAs among gym users. RESULTS: About 70% of 316 participants had
      used one or more of PEAs over the last six months. Of those, about 68.4% used
      protein powder supplements and 48.1% used energy drinks. Participants who
      believed that protein powder supplements (c2=52.3, P < .01) and energy drinks
      (c2=35.2, P < .01) had health hazards used these agents less often than others
      during the six months preceding data collection. Participants who had less
      knowledge about the negative health consequences were more likely to use protein
      powder supplement (t=2.38, P=.018). On the other hand, those who were more
      knowledgeable about the negative health consequences of insulin, were more likely
      to use insulin (t=2.45, P=.015). CONCLUSION: Misuse of PEAs is widespread among
      gym users in Saudi Arabia. Improving the level of knowledge and awareness of
      possible serious health consequences would hopefully lead to reduced PEA
      consumption. LIMITATIONS: The temporal sequence of cause and effect could not be
      determined in a cross sectional study. Convenience sampling in a single city
      limited the generalizability of the findings to all regions of Saudi Arabia.

PMID- 28761033
TI  - Perception of hospital accreditation among health professionals in Saudi Arabia.
AB  - BACKGROUND: Hospital accreditation assesses hospital performance against explicit
      standards. Studies of the efficacy of accreditation are limited, but suggest that
      Joint Commission International (JCI) accreditation is efficient in improving the
      safety and quality of care in accredited hospitals. OBJECTIVES: This study aimed
      to assess the perceptions of health professionals on the impact of JCI
      accreditation and implementation of change towards the delivery of quality
      patient care. DESIGN: Cross-sectional survey. SETTINGS: King Abdulaziz Medical
      City in Jeddah, Saudi Arabia. SUBJECTS: Between June 2016 and September 2016, a
      validated questionnaire was distributed to physicians, nurses, medical
      technologists, dietitians, and other allied healthcare professionals. The
      questionnaire consisted of 19 items covering participation in accreditation,
      benefits of accreditation, and the quality of results of accreditation.
      Demographic data collected on the participants included age, gender, educational
      attainment, profession, length of service, and department. MAIN OUTCOME
      MEASURE(S): Participation in accreditation, benefits of accreditation, and
      quality of results of accreditation. RESULTS: Hospital accreditation was given a
      worthy response from the general view of 901 health professionals. The mean
      (standard deviation) of scores on a 5-point Likert scale were 3.79 (0.68) for
      participation in accreditation, 3.85 (0.84) for benefits, and 3.54 (1.01) for
      quality of results. CONCLUSION: As perceived by health professionals in our
      survey, accrediation had a positive impact on the process and implementation of
      change in the hospital that resulted in improvement in the delivery of patient
      care and other health services. LIMITATIONS: Single institution study with no
      comparison made to other small, medium, or large-sized JCI-accredited hospitals
      in Saudi Arabia. Patient satisfaction before and after accreditation was not
      included.

PMID- 28761034
TI  - Successful desensitization to radiocontrast media in two high-risk cardiac
      patients.
AB  - : Hypersensitivity reactions to radiocontrast media (RCM) are common and in
      severe cases may present a challenge for treating physician in cases when
      premedication fails or the patient presents with severe comorbidities. We
      describe two cases in need of radiocontrast media after a severe reaction on
      previous exposure to iohexol. One presented anaphylactic reaction to RCM despite
      premedication and another presented with angina. Both cases were treated with a
      desensitization protocol to iodixanol. In conclusion, desensitization to
      radiocontrast media may be considered in patients with previously unsuccessful
      premedication and/or severe acute comorbidities. SIMILAR CASES PUBLISHED: 14.

PMID- 28761035
TI  - Accessory ulna: a rare case in an Asian female.

PMID- 28761036
TI  - RE: Association of human leukocyte antigen-DRB1 with anti-cyclic citrullinated
      peptide autoantibodies in Saudi patients with rheumatoid arthritis.

PMID- 28761037
TI  - Reply.

PMID- 28761038
TI  - Erratum.

PMID- 28761039
TI  - Atrio-Esophageal Fistula: A Case Series and Literature Review.
AB  - BACKGROUND Percutaneous catheter radiofrequency ablation (RFA) and cryoablation
      of the left atrium and pulmonary vein ostia have become successful therapeutic
      modalities in the management of atrial fibrillation. Atrio-esophageal fistula is
      a rare complication. Awareness of complication risk is imperative because without
      prompt diagnosis and urgent surgical intervention, the outcome is often fatal. We
      present 3 cases of atrio-esophageal fistula following percutaneous catheter
      radiofrequency ablation (RFA). CASE REPORT Case 1: A 72-year old white male
      presented 27 days after percutaneous RFA for atrial fibrillation with fever,
      altered mental status, and melena. Esophagogastroduodenoscopy (EGD) revealed a 1
      cm defect in the mid-esophagus. Upon thoracotomy, severe hemorrhage ensued from a
      concomitant injury to the left atrium. Multiple attempts to repair the left
      atrial perforation were unsuccessful and the patient died. Case 2: A 71-year old
      white male presented 29 days after percutaneous RFA for atrial fibrillation with
      fever and tonic-clonic seizure. Recognition of possible atrio-esophageal fistula
      was considered and confirmed on thoracotomy. Surgical fixation of the left atria
      and esophagus were performed. The patient survived and was discharged to a
      skilled care facility. Case 3: A 75-year old white male presented 24 days after
      percutaneous RFA for atrial fibrillation with chest pain. An echocardiogram
      revealed a large pericardial effusion and pericardiocentesis was performed.
      Despite aggressive measures, the patient died. The autopsy demonstrated a
      communicating esophageal fistula with the right pulmonary vein. CONCLUSIONS
      Clinicians tending to patients who have recently undergone atrial ablation need
      to be aware of atrio-esophageal fistula as a rare but highly fatal complication.

PMID- 28761040
TI  - Microsatellite and Single Nucleotide Polymorphisms in the Insulin-Like Growth
      Factor 1 Promoter with Insulin Sensitivity and Insulin Secretion.
AB  - BACKGROUND To investigate associations of the CA microsatellite and rs35767,
      rs5742612, and rs2288377 polymorphisms and the single nucleotide polymorphism
      (SNP) haplotypes with and without the CA microsatellite in the IGF1 promoter with
      insulin sensitivity and secretion. MATERIAL AND METHODS The CA microsatellite and
      SNPs were genotyped in 389 type 2 diabetes mellitus (T2DM) patients. A 75 g oral
      glucose tolerance test (OGTT) was given to all the participants. Associations of
      the genotypes and haplotypes with insulin sensitivity, insulin secretion, glucose
      tolerance, and insulin-like growth factor 1 (IGF1) were analyzed by ANCOVA
      (general linear model) and multiple linear regression, after controlling for
      gender, age, and BMI. RESULTS The CA microsatellite, rs35767 polymorphisms, and
      SNP haplotypes with or without CA showed no significant association with
      metabolic parameters. The C allele of rs5742612 was found to be associated with
      decreased insulin sensitivity (HOMA-S index, beta=-0.131, P=0.008; fasting
      insulin level, beta=0.022, P=0.006) and increased insulin secretion (HOMA-B
      index, beta=0.099, P=0.008; insulin AUC, beta=0.112, P=0.012). The linear
      regression model also indicated that the A allele of rs2288377 was associated
      with decreased insulin sensitivity (HOMA-S index, beta=-0.159, P=0.001; fasting
      insulin, beta=0.143, P=0.001) and increased insulin secretion (HOMA-B index,
      beta=0.114, P=0.017; insulin AUC, beta=0.042, P=0.002). CONCLUSIONS The CA
      microsatellite and rs35767 have no genotype-related difference in insulin
      sensitivity or secretion. The rs5742612 and rs2288377 polymorphisms are
      significantly associated with insulin biology, with the TT genotype exhibiting
      higher insulin sensitivity and lower insulin secretion compared with carriers of
      the C allele and A allele, respectively, mostly attributed to the direct
      functional roles of the two loci.

PMID- 28761041
TI  - Modified Western blotting for insulin and other diabetes-associated peptide
      hormones.
AB  - Now, the quantification of proinsulin/insulin contents within organisms tends to
      be evaluated only by enzyme-linked immunosorbent assay (ELISA), although
      assessing the adequacy of results by some quantification method is important.
      Remarkably, few scientific papers use detection by Western blotting (WB), another
      immunological assay, of proinsulin/insulin. We found two problems with
      quantification of insulin and proinsulin by general WB: the shape of an insulin
      band in gel electrophoresis is distorted, and the retention potency to a blotting
      membrane of the peptide hormones (mainly insulin) is low. We solved the first
      problem by optimizing the sodium dodecyl sulfate concentration in the sample
      buffer and the second problem by glutaraldehyde fixation following treatment with
      a blocking solution for a short time. The improvements were confirmed by
      quantification of proinsulin/insulin in standards, MIN6c4 cell lysates, and
      MIN6c4 culture supernatants. Furthermore, we showed that the modified WB is
      applicable to other diabetes-associated peptide hormones: insulin analogs,
      glucagon, GLP-1s, somatostatins, ghrelins, and pancreatic polypeptide. Our data
      showed that the modified WB can contribute to qualitative or quantitative
      analyses of diabetes-associated peptides by providing analytical information
      based on electrophoresis, although ELISA, which is an almost exclusive method in
      the quantification of peptide hormones, supplies only numerical data.

PMID- 28761042
TI  - A dsRNA virus with filamentous viral particles.
AB  - Viruses with double-stranded RNA genomes form isometric particles or are
      capsidless. Here we report a double-stranded RNA virus, Colletotrichum camelliae
      filamentous virus 1 (CcFV-1) isolated from a fungal pathogen, that forms
      filamentous particles. CcFV-1 has eight genomic double-stranded RNAs, ranging
      from 990 to 2444 bp, encoding 10 putative open reading frames, of which open
      reading frame 1 encodes an RNA-dependent RNA polymerase and open reading frame 4
      a capsid protein. When inoculated, the naked CcFV-1 double-stranded RNAs are
      infectious and induce the accumulation of the filamentous particles in vivo. CcFV
      1 is phylogenetically related to Aspergillus fumigatus tetramycovirus-1 and
      Beauveria bassiana polymycovirus-1, but differs in morphology and in the number
      of genomic components. CcFV-1 might be an intermediate virus related to truly
      capsidated viruses, or might represent a distinct encapsidating strategy. In
      terms of genome and particle architecture, our findings are a significant
      addition to the knowledge of the virosphere diversity.Viruses with double
      stranded RNA (dsRNA) genomes form typically isometric particles or are capsid
      less. Here, the authors identify a mycovirus with an eight-segmented dsRNA genome
      that forms exceptionally long filamentous particles and could represent an
      evolutionary link between ssRNA and dsRNA viruses.

PMID- 28761043
TI  - Diurnal preference, mood and the response to morning light in relation to
      polymorphisms in the human clock gene PER3.
AB  - PER3 gene polymorphisms have been associated with differences in human sleep-wake
      phenotypes, and sensitivity to light. The aims of this study were to assess: i)
      the frequency of allelic variants at two PER3 polymorphic sites (rs57875989
      length polymorphism: PER3 4, PER3 5; rs228697 SNP: PER3 C, PER3 G) in relation to
      sleep-wake timing; ii) the effect of morning light on behavioural/circadian
      variables in PER3 4 /PER3 4 and PER3 5 /PER3 5 homozygotes. 786 Caucasian
      subjects living in Northern Italy donated buccal DNA and completed diurnal
      preference, sleep quality/timing and sleepiness/mood questionnaires. 19 PER3 4
      /PER3 4 and 11 PER3 5 /PER3 5 homozygotes underwent morning light administration,
      whilst monitoring sleep-wake patterns and the urinary 6-sulphatoxymelatonin
      (aMT6s) rhythm. No significant relationship was observed between the length
      polymorphism and diurnal preference. By contrast, a significant association was
      observed between the PER3 G variant and morningness (OR = 2.10), and between the
      PER3 G-PER3 4 haplotype and morningness (OR = 2.19), for which a mechanistic
      hypothesis is suggested. No significant differences were observed in sleep
      timing/aMT6s rhythms between PER3 5 /PER3 5 and PER3 4 /PER3 4 subjects at
      baseline. After light administration, PER3 4 /PER3 4 subjects advanced their
      aMT6s acrophase (p < 0.05), and showed a trend of advanced sleep-wake timing. In
      conclusion, significant associations were observed between PER3 polymorphic
      variants/their combinations and both diurnal preference and the response to
      light.

PMID- 28761044
TI  - Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase
      complex in colon cancer cells.
AB  - Resveratrol (RES), a polyphenol found in natural foods, displays anti-oxidant,
      anti-inflammatory and anti-proliferative properties potentially beneficial in
      cancers, in particular in the prevention of tumor growth. However, the rapid
      metabolism of resveratrol strongly limits its bioavailability. The molecular
      mechanisms sustaining the potential biological activity of low doses of
      resveratrol has not been extensively studied and, thus, needs better
      characterization. Here, we show that resveratrol (10 uM, 48 hr) induces both a
      cell growth arrest and a metabolic reprogramming in colon cancer cells.
      Resveratrol modifies the lipidomic profile, increases oxidative capacities and
      decreases glycolysis, in association with a decreased pentose phosphate activity
      and an increased ATP production. Resveratrol targets the pyruvate dehydrogenase
      (PDH) complex, a key mitochondrial gatekeeper of energy metabolism, leading to an
      enhanced PDH activity. Calcium chelation, as well as the blockade of the
      mitochondrial calcium uniport, prevents the resveratrol-induced augmentation in
      oxidative capacities and the increased PDH activity suggesting that calcium might
      play a role in the metabolic shift. We further demonstrate that the inhibition of
      the CamKKB or the downstream AMPK pathway partly abolished the resveratrol
      induced increase of glucose oxidation. This suggests that resveratrol might
      improve the oxidative capacities of cancer cells through the CamKKB/AMPK pathway.

PMID- 28761045
TI  - Salmonella typhimurium-induced IL-1 release from primary human monocytes requires
      NLRP3 and can occur in the absence of pyroptosis.
AB  - Large molecular complexes known as inflammasomes regulate the release of IL-1beta
      from immune cells in response to infection and injury. Salmonella typhimurium
      infection is reported to activate NLRP3 and NLRC4 inflammasomes which are
      subsequently involved in pyroptosis of the cell and pathogen clearance. However,
      the response to S. typhimurium in primary human monocytes has not been studied in
      detail. The aim of this study was to investigate the effect of S. typhimurium on
      inflammasomes in primary human monocytes. Much of the previous research in the
      field has been conducted in murine models and human THP-1 cells, which may not
      reflect the responses of primary human monocytes. Here, we report that inhibiting
      NLRP3 with the selective inhibitor MCC950, blocked release of IL-1beta and the
      related cytokine IL-1alpha from primary human monocytes in response to S.
      typhimurium. Additionally, under these conditions S. typhimurium-induced IL-1
      release occurred independently of pyroptosis. We propose that IL-1beta release
      without pyroptosis may occur in early-recruited monocytes to regulate a maximal
      innate immune response to Salmonella infection, allowing a sustained inflammatory
      signal. This insight into the mechanisms involved in IL-1 release from primary
      human monocytes highlights major differences between immune cell types, and the
      defences they employ during bacterial infection.

PMID- 28761046
TI  - Fungal community succession and major components change during manufacturing
      process of Fu brick tea.
AB  - Fu brick tea is a unique post-fermented tea product which is fermented with
      microorganism during the manufacturing process. Metabolic analysis showed that
      most metabolites content were decreased during the manufacturing process of Fu
      brick tea, except GA (gallic acid). Illumina MiSeq sequencing of ITS gene
      amplicons was applied to analyze the fungal community succession. The genera
      Aspergillus, Cyberlindnera and Candida were predominant at the early stage of
      manufacturing process (from "primary dark tea" to "fermentation for 3 days"), but
      after the stage of "fermentation for 3 days" only Aspergillus was still
      dominated, and maintain a relatively constant until to the end of manufacturing
      process. The effects of metabolites on the structure of the fungal community were
      analyzed by redundancy analysis (RDA) and variation partitioning analysis (VPA).
      The results indicated that GCG (gallocatechin gallate), EGCG (epigallocatechin
      gallate) and GA as well as the interactions among them were the most probably
      ones to influence, or be influenced by the fungal communities during the
      fermentation process of Fu brick tea. This study revealed fungal succession,
      metabolite changes and their relationships, provided new insights into the
      mechanisms for manufacturing process of Fu brick tea.

PMID- 28761047
TI  - Sustained and Cost Effective Silver Substrate for Surface Enhanced Raman
      Spectroscopy Based Biosensing.
AB  - While surface enhanced Raman spectroscopy (SERS) based biosensing has
      demonstrated great potential for point-of-care diagnostics in the laboratory, its
      application in the field is limited by the short life time of commonly used
      silver based SERS active substrates. In this work, we report our attempt towards
      SERS based field biosensing, involving the development of a novel sustained and
      cost-effective substrate composed of silver nanoparticles protected by small
      nitrogen-doped Graphene Quantum Dots, i.e. Ag NP@N-GQD, and its systematic
      evaluation for glucose sensing. The new substrate demonstrated significantly
      stronger Raman enhancement compared to pure silver nanoparticles. More
      importantly, the new substrate preserved SERS performance in a normal indoor
      environment for at least 30 days in both the wet and dry states, in contrast to
      only 10 days for pure silver nanoparticles. The Ag NP@N-GQD thin film in the dry
      state was then successfully applied as a SERS substrate for glucose detection in
      mouse blood samples. The new substrate was synthesized under mild experimental
      conditions, and the cost increase due to N-GQD was negligible. These results
      suggest that the Ag NP@N-GQD is a cost-effective and sustained SERS substrate,
      the development of which represents an important step towards SERS based field
      biosensing.

PMID- 28761048
TI  - Optoacoustic micro-tomography at 100 volumes per second.
AB  - Optical microscopy remains a fundamental tool for modern biological discovery
      owing to its excellent spatial resolution and versatile contrast in visualizing
      cellular and sub-cellular structures. Yet, the time domain is paramount for the
      observation of biological dynamics in living systems. Commonly, acquisition of
      microscopy data involves scanning of a spherically- or cylindrically-focused
      light beam across the imaged volume, which significantly limits temporal
      resolution in 3D. Additional complications arise from intense light scattering of
      biological tissues, further restraining the effective penetration depth and field
      of view of optical microscopy techniques. To overcome these limitations, we
      devised a fast optoacoustic micro-tomography (OMT) approach based on simultaneous
      acquisition of 3D image data with a high-density hemispherical ultrasound array
      having effective detection bandwidth beyond 25 MHz. We demonstrate fast three
      dimensional imaging of freely-swimming zebrafish larvae, achieving 3D imaging
      speed of 100 volumes per second with isotropic spatial resolution approaching the
      dimensions of large cells across a field of view exceeding 50mm3. As opposed to
      other microscopy techniques based on optical contrast, OMT resolves optical
      absorption acoustically using unfocused light excitation. Thus, no penetration
      barriers are imposed by light scattering in deep tissues, suggesting it as a
      powerful approach for multi-scale functional and molecular imaging applications.

PMID- 28761049
TI  - Improving cartilage phenotype from differentiated pericytes in tunable peptide
      hydrogels.
AB  - Differentiation of stem cells to chondrocytes in vitro usually results in a
      heterogeneous phenotype. This is evident in the often detected over expression of
      type X collagen which, in hyaline cartilage structure is not characteristic of
      the mid-zone but of the deep-zone ossifying tissue. Methods to better match
      cartilage developed in vitro to characteristic in vivo features are therefore
      highly desirable in regenerative medicine. This study compares phenotype
      characteristics between pericytes, obtained from human adipose tissue,
      differentiated using diphenylalanine/serine (F2/S) peptide hydrogels with the
      more widely used chemical induced method for chondrogenesis. Significantly higher
      levels of type II collagen were noted when pericytes undergo chondrogenesis in
      the hydrogel in the absence of induction media. There is also a balanced
      expression of collagen relative to aggrecan production, a feature which was
      biased toward collagen production when cells were cultured with induction media.
      Lastly, metabolic profiles of each system show considerable overlap between both
      differentiation methods but subtle differences which potentially give rise to
      their resultant phenotype can be ascertained. The study highlights how material
      and chemical alterations in the cellular microenvironment have wide ranging
      effects on resultant tissue type.

PMID- 28761050
TI  - Non-labeling multiphoton excitation microscopy as a novel diagnostic tool for
      discriminating normal tissue and colorectal cancer lesions.
AB  - Multiphoton excitation microscopy (MPM) is regarded as an effective tool that
      enables the visualization of deep regions within living tissues and organs, with
      little damage. Here, we report novel non-labeling MPM (NL-MPM) imaging of fresh
      human colorectal mucosa, which is useful for discriminating cancer lesions from
      normal tissues quantitatively without any need for resection, fixation, or
      staining. Using NL-MPM, we visualized three components in human colorectal
      mucosa, epithelial cells, immune cells, and basement membranes, based on their
      characteristic patterns of fluorescence. These patterns are characterized by the
      different auto-fluorescence properties of nicotinamide adenine dinucleotide,
      nicotinamide adenine dinucleotide phosphate, and flavin adenine dinucleotide and
      from second harmonic generation (SHG). NL-MPM images were at least as informative
      to pathologists as were 'conventional' images of fixed tissue sections stained
      with hematoxylin and eosin. Additionally, two quantitative parameters extracted
      from NL-MPM images - the nucleus diameter (index N) and the intensity of SHG in
      the basement membrane (index S) - rendered it possible to diagnose cancer regions
      effectively. In conclusion, NL-MPM is a novel, promising method for real-time
      clinical diagnosis of colorectal cancers, and is associated with minimal
      invasiveness.

PMID- 28761051
TI  - Interface-induced spontaneous positive and conventional negative exchange bias
      effects in bilayer La0.7Sr0.3MnO3/Eu0.45Sr0.55MnO3 heterostructures.
AB  - We report zero-field-cooled spontaneous-positive and field-cooled conventional
      negative exchange bias effects in epitaxial bilayer composed of La0.7Sr0.3MnO3
      (LSMO) with ferromagnetic (FM) and Eu0.45Sr0.55MnO3 (ESMO) with A-type
      antiferromagnetic (AF) heterostructures respectively. A temperature dependent
      magnetization study of LSMO/ESMO bilayers grown on SrTiO3 (001) manifest FM
      ordering (TC) of LSMO at ~320 K, charge/orbital ordering of ESMO at ~194 K and AF
      ordering (TN) of ESMO at ~150 K. The random field Ising model has demonstrated an
      interesting observation of inverse dependence of exchange bias effect on AF layer
      thickness due to the competition between FM-AF interface coupling and AF domain
      wall energy. The isothermally field induced unidirectional exchange anisotropy
      formed at the interface of FM-LSMO layer and the kinetically phase-arrested
      magnetic phase obtained from the metamagnetic AF-ESMO layer could be responsible
      for the spontaneous exchange bias effect. Importantly, no magnetic poling is
      needed, as necessary for the applications. The FM-AF interface exchange
      interaction has been ascribed to the AF coupling with [Formula: see text]
      ([Formula: see text], coupling constant between AF spins) for the spontaneous
      positive hysteresis loop shift, and the field-cooled conventional exchange bias
      has been attributed to the ferromagnetically exchanged interface with [Formula:
      see text] (coupling constant between FM spins).

PMID- 28761052
TI  - UCHL1-HIF-1 axis-mediated antioxidant property of cancer cells as a therapeutic
      target for radiosensitization.
AB  - Hypoxia-inducible factor 1 (HIF-1) has been recognized as an important mediator
      of the reprogramming of carbohydrate metabolic pathways from oxidative
      phosphorylation to accelerated glycolysis. Although this reprogramming has been
      associated with the antioxidant and radioresistant properties of cancer cells,
      gene networks triggering the HIF-1-mediated reprogramming and molecular
      mechanisms linking the reprogramming with radioresistance remain to be
      determined. Here, we show that Ubiquitin C-terminal hydrolase-L1 (UCHL1), which
      we previously identified as a novel HIF-1 activator, increased the
      radioresistance of cancer cells by producing an antioxidant, reduced glutathione
      (GSH), through HIF-1-mediated metabolic reprogramming. A luciferase assay to
      monitor HIF-1 activity demonstrated that the overexpression of UCHL1, but not its
      deubiquitination activity-deficient mutant (UCHL1 C90S), upregulated HIF-1
      activity by stabilizing the regulatory subunit of HIF-1 (HIF-1alpha) in a murine
      breast cancer cell line, EMT6. UCHL1 overexpression induced the reprogramming of
      carbohydrate metabolism and increased NADPH levels in a pentose phosphate pathway
      (PPP)-dependent manner. The UCHL1-mediated reprogramming elevated intracellular
      GSH levels, and consequently induced a radioresistant phenotype in a HIF-1
      dependent manner. The pharmacological inhibition of PPP canceled the UCHL1
      mediated radioresistance. These results collectively suggest that cancer cells
      acquire antioxidant and radioresistant phenotypes through UCHL1-HIF-1-mediated
      metabolic reprogramming including the activation of PPP and provide a rational
      basis for targeting this gene network for radiosensitization.

PMID- 28761053
TI  - Laser induced strong-field ionization gas jet tomography.
AB  - We introduce a novel in-situ strong field ionization tomography approach for
      characterizing the spatial density distribution of gas jets. We show that for
      typical intensities in high harmonic generation experiments, the strong field
      ionization mechanism used in our approach provides an improvement in the
      resolution close to factor of 2 (resolving about 8 times smaller voxel volume),
      when compared to linear/single-photon imaging modalities. We find, that while the
      depth of scan in linear tomography is limited by resolution loss due to the
      divergence of the driving laser beam, in the proposed approach the depth of focus
      is localized due to the inherent physical nature of strong-field interaction and
      discuss implications of these findings. We explore key aspects of the proposed
      method and compare it with commonly used single- and multi-photon imaging
      mechanisms. The proposed method will be particularly useful for strong field and
      attosecond science experiments.

PMID- 28761054
TI  - Using latent class cluster analysis to screen high risk clusters of birth defects
      between 2009 and 2013 in Northwest China.
AB  - In the study, we aimed to explore the synergistic effects of multiple risk
      factors on birth defects, and examine temporal trend of the synergistic effects
      over time. Two cross-sectional surveys conducted in 2009 and 2013 were merged and
      then latent class cluster analysis and generalized linear Poisson model were
      used. A total of 9085 and 29094 young children born within the last three years
      and their mothers were enrolled in 2009 and 2013 respectively. Three latent
      maternal exposure clusters were determined: a high-risk, a moderate-risk, and a
      low-risk cluster (88.97%, 1.49%, 9.54% in 2009 and 82.42%, 3.39%, 14.19% in
      2013). The synthetic effects of maternal exposure to multiple risk factors could
      increase the risk of overall birth defects and cardiovascular system malformation
      among live births, and this risk is significantly higher in high-risk cluster
      than that in low-risk cluster. After adjusting for confounding factors using a
      generalized linear Poisson model, in high-risk cluster the prevalence of nervous
      system malformation decreased by approximately 2.71%, and the proportion of
      cardiovascular system malformation rose by 0.92% from 2009 to 2013. The Chinese
      government should make great efforts to provide primary prevention for those on
      high-risk cluster as a priority target population.

PMID- 28761056
TI  - Image Cytometric Analysis of Algal Spores for Evaluation of Antifouling
      Activities of Biocidal Agents.
AB  - Chemical biocides have been widely used as marine antifouling agents, but their
      environmental toxicity impose regulatory restriction on their use. Although
      various surrogate antifouling biocides have been introduced, their comparative
      effectiveness has not been well investigated partly due to the difficulty of
      quantitative evaluation of their antifouling activity. Here we report an image
      cytometric method to quantitatively analyze the antifouling activities of seven
      commercial biocides using Ulva prolifera as a target organism, which is known to
      be a dominant marine species causing soft fouling. The number of spores settled
      on a substrate is determined through image analysis using the intrinsic
      fluorescence of chlorophylls in the spores. Pre-determined sets of size and shape
      of spores allow for the precise determination of the number of settled spores.
      The effects of biocide concentration and combination of different biocides on the
      spore settlement are examined. No significant morphological changes of Ulva
      spores are observed, but the amount of adhesive pad materials is appreciably
      decreased in the presence of biocides. It is revealed that the growth rate of
      Ulva is not directly correlated with the antifouling activities against the
      settlement of Ulva spores. This work suggests that image cytometric analysis is a
      very convenient, fast-processable method to directly analyze the antifouling
      effects of biocides and coating materials.

PMID- 28761055
TI  - A single-channel mechanism for pharmacological potentiation of GluN1/GluN2A NMDA
      receptors.
AB  - NMDA receptors (NMDARs) contribute to several neuropathological processes. Novel
      positive allosteric modulators (PAMs) of NMDARs have recently been identified but
      their effects on NMDAR gating remain largely unknown. To this end, we tested the
      effect of a newly developed molecule UBP684 on GluN1/GluN2A receptors. We found
      that UBP684 potentiated the whole-cell currents observed under perforated-patch
      conditions and slowed receptor deactivation. At the single channel level, UBP684
      produced a dramatic reduction in long shut times and a robust increase in mean
      open time. These changes were similar to those produced by NMDAR mutants in which
      the ligand-binding domains (LBDs) are locked in the closed clamshell conformation
      by incorporating a disulfide bridge. Since the locked glutamate-binding clefts
      primarily contributes to receptor efficacy these results suggests that UBP684
      binding may induce switch in conformation similar to glutamate LBD locked state.
      Consistent with this prediction UBP684 displayed greater potentiation of NMDARs
      with only the GluN1 LBD locked compared to NMDARs with only the GluN2 LBD locked.
      Docking studies suggest that UBP684 binds to the GluN1 and GluN2 LBD interface
      supporting its potential ability in stabilizing the LBD closed conformation.
      Together these studies identify a novel pharmacological mechanism of facilitating
      the function of NMDARs.

PMID- 28761057
TI  - Development of Series of Affinity Tags in Streptomyces.
AB  - Streptomyces are of great biological and industrial significance due to their
      complex morphological development and ability to produce numerous secondary
      metabolites. However, the intrinsic biochemical mechanisms underlying
      morphogenesis and secondary metabolism are rarely revealed, partially because of
      the limited availability of the biochemical tools in Streptomyces. Here we
      provided series of integrative vectors with various affinity tags, including
      single tags 3*FLAG, 3*HA, 3*Strep-tag II, 18*His, 13*Myc, and dual tags, all of
      which were driven from a strong constitutive promoter ermEp*. Using a sigma
      factor SigT from S. coelicolor as a model, we successfully expressed and immuno
      detected SigT fused with all tags. Moreover, after SigT was N-terminally tagged
      with 3*FLAG and C-terminally tagged with 18*His, we isolated SigT-interactive
      proteins from the S. coelicolor lysate based on the tandem affinity purification
      (TAP). Particularly, among the proteins purified, the SigT cognate anti-sigma
      factor RstA ranked the top with the most total independent spectra. These data
      suggested the feasibility of these affinity tags in Streptomyces, which will be
      widely employed to explore the biochemical mechanisms to further understand the
      dynamic and elaborate regulation in this genus.

PMID- 28761059
TI  - Prediction of aboveground grassland biomass on the Loess Plateau, China, using a
      random forest algorithm.
AB  - Grasslands are an important component of terrestrial ecosystems that play a
      crucial role in the carbon cycle and climate change. In this study, we collected
      aboveground biomass (AGB) data from 223 grassland quadrats distributed across the
      Loess Plateau from 2011 to 2013 and predicted the spatial distribution of the
      grassland AGB at a 100-m resolution from both meteorological station and remote
      sensing data (TM and MODIS) using a Random Forest (RF) algorithm. The results
      showed that the predicted grassland AGB on the Loess Plateau decreased from east
      to west. Vegetation indexes were positively correlated with grassland AGB, and
      the normalized difference vegetation index (NDVI) acquired from TM data was the
      most important predictive factor. Tussock and shrub tussock had the highest AGB,
      and desert steppe had the lowest. Rainfall higher than 400 m might have
      benefitted the grassland AGB. Compared with those obtained for the bagging,
      mboost and the support vector machine (SVM) models, higher values for the mean
      Pearson coefficient (R) and the symmetric index of agreement (lambda) were
      obtained for the RF model, indicating that this RF model could reasonably
      estimate the grassland AGB (65.01%) on the Loess Plateau.

PMID- 28761058
TI  - Heterogeneity of tumor-infiltrating lymphocytes ascribed to local immune status
      rather than neoantigens by multi-omics analysis of glioblastoma multiforme.
AB  - Hypothetically, intratumoral genomic heterogeneity has the potential to foster
      tumor-infiltrating lymphocyte (TIL) diversity; however, no study has directly
      tested this hypothesis by simultaneously investigating somatic mutations, TIL
      diversity, and immune response activity. Thus, we performed whole-exome
      sequencing, immune repertoire sequencing and gene expression on ten spatially
      separated tumor samples obtained from two tumor masses excised from a
      glioblastoma multiforme (GBM) patient, and we included peripheral blood as
      control. We found that although the multi-region samples from one tumor shared
      more common mutations than those from different tumors, the TIL populations did
      not. TIL repertoire diversity did not significantly correlate with the number of
      non-synonymous mutations; however, TIL diversity was highly correlated with local
      immune activity, as the pathways were all immune-related pathways that highly
      positive correlated with local TIL diversity. Twenty-three genes with expression
      largely unaffected by the intratumor heterogeneity were extracted from these
      pathways. Fifty GBM patients were stratified into two clusters by the expression
      of these genes with significant difference in prognosis. This finding was
      validated by The Cancer Genome Atlas (TCGA) GBM dataset, which indicated that
      despite the heterogeneity of intra-tumor immune status, the overall level of the
      immune response in GBM could be connected with prognosis.

PMID- 28761060
TI  - Administration of Lactobacillus salivarius LI01 or Pediococcus pentosaceus LI05
      prevents CCl4-induced liver cirrhosis by protecting the intestinal barrier in
      rats.
AB  - Alterations in the gut microbiome have been reported in liver cirrhosis, and
      probiotic interventions are considered a potential treatment strategy. This study
      aimed to evaluate the effects and mechanisms of Lactobacillus salivarius LI01,
      Pediococcus pentosaceus LI05, Lactobacillus rhamnosus GG, Clostridium butyricum
      MIYAIRI and Bacillus licheniformis Zhengchangsheng on CCl4-induced cirrhotic
      rats. Only administration of LI01 or LI05 prevented liver fibrosis and down
      regulated the hepatic expression of profibrogenic genes. Serum endotoxins,
      bacterial translocations (BTs), and destruction of intestinal mucosal
      ultrastructure were reduced in rats treated with LI01 or LI05, indicating
      maintenance of the gut barrier as a mechanism; this was further confirmed by the
      reduction of not only hepatic inflammatory cytokines, such as TNF-alpha, IL-6,
      and IL-17A, but also hepatic TLR2, TLR4, TLR5 and TLR9. Metagenomic sequencing of
      16S rRNA gene showed an increase in potential beneficial bacteria, such as
      Elusimicrobium and Prevotella, and a decrease in pathogenic bacteria, such as
      Escherichia. These alterations in gut microbiome were correlated with
      profibrogenic genes, gut barrier markers and inflammatory cytokines. In
      conclusion, L. salivarius LI01 and P. pentosaceus LI05 attenuated liver fibrosis
      by protecting the intestinal barrier and promoting microbiome health. These
      results suggest novel strategies for the prevention of liver cirrhosis.

PMID- 28761061
TI  - TEPAPA: a novel in silico feature learning pipeline for mining prognostic and
      associative factors from text-based electronic medical records.
AB  - Vast amounts of clinically relevant text-based variables lie undiscovered and
      unexploited in electronic medical records (EMR). To exploit this untapped
      resource, and thus facilitate the discovery of informative covariates from
      unstructured clinical narratives, we have built a novel computational pipeline
      termed Text-based Exploratory Pattern Analyser for Prognosticator and Associator
      discovery (TEPAPA). This pipeline combines semantic-free natural language
      processing (NLP), regular expression induction, and statistical association
      testing to identify conserved text patterns associated with outcome variables of
      clinical interest. When we applied TEPAPA to a cohort of head and neck squamous
      cell carcinoma patients, plausible concepts known to be correlated with human
      papilloma virus (HPV) status were identified from the EMR text, including site of
      primary disease, tumour stage, pathologic characteristics, and treatment
      modalities. Similarly, correlates of other variables (including gender, nodal
      status, recurrent disease, smoking and alcohol status) were also reliably
      recovered. Using highly-associated patterns as covariates, a patient's HPV status
      was classifiable using a bootstrap analysis with a mean area under the ROC curve
      of 0.861, suggesting its predictive utility in supporting EMR-based phenotyping
      tasks. These data support using this integrative approach to efficiently identify
      disease-associated factors from unstructured EMR narratives, and thus to
      efficiently generate testable hypotheses.

PMID- 28761063
TI  - Elevated levels of the stress hormone, corticosterone, cause 'pessimistic'
      judgment bias in broiler chickens.
AB  - Pessimistic judgment biases, whereby humans or non-human animals interpret
      ambiguous information negatively, are hypothesised to be one of the suite of
      adaptive changes that comprise the vertebrate stress response. To test this
      hypothesis, we asked whether experimentally elevating levels of the
      glucocorticoid stress hormone, corticosterone, in broiler chickens produced a
      pessimistic judgment bias. We trained young chickens to discriminate a stimulus
      (paper cone) placed at two locations in an arena, one associated with reward
      (mealworms) and one with punishment (air puff). During seven days of non-invasive
      administration of either corticosterone or vehicle control, we tested the birds'
      responses to the cone placed at ambiguous locations between the trained
      locations. Corticosterone-treated birds were more likely than controls to respond
      as if punishment was likely when the cone was placed near to the punished
      location. The degree of this 'pessimism' was associated with smaller relative
      spleen weight, which is a documented consequence of chronic stress in chickens.
      We conclude that changes in corticosterone levels in chickens are sufficient to
      cause a specific change in decision making, dubbed 'pessimism', whereby
      corticosterone-treated birds showed an increased expectation of punishment in the
      face of ambiguous information. Pessimism could be a useful welfare indicator in
      chickens.

PMID- 28761064
TI  - The enzymatic epimerization of deoxynivalenol by Devosia mutans proceeds through
      the formation of 3-keto-DON intermediate.
AB  - The enzymatic detoxification of deoxynivalenol (DON) is a promising mitigation
      strategy for addressing this mycotoxin contamination of cereal grains. A recently
      described bacterium, Devosia mutans 17-2-E-8, capable of transforming DON into
      its non-toxic stereoisomer 3-epi-DON, holds promise for the development of such
      applications. Earlier observations suggested that DON epimerization proceeds via
      a two-step catalysis with 3-keto-DON as an intermediate. The results of this
      study indicate that NADPH is required for DON epimerization by cell-free protein
      extracts of D. mutans, while high concentrations of glucose and sucrose have a
      suppressive effect. Chemically synthesized 3-keto-DON incubated with D. mutans
      protein fractions enriched by ammonium sulfate precipitation at 35-55% saturation
      selectively reduced 3-keto-DON to 3-epi-DON, but fell short of supporting the
      complete epimerization of DON. In addition, seven Devosia species investigated
      for DON epimerization were all able to reduce 3-keto-DON to 3-epi-DON, but only a
      few were capable of epimerizing DON. The above observations collectively confirm
      that the enzymes responsible for the oxidation of DON to 3-keto-DON are
      physically separate from those involved in 3-keto-DON reduction to 3-epi-DON. The
      enzymatic nature of DON epimerization suggests that the process could be used to
      develop genetically engineered crops or microorganisms, ultimately reducing
      foodborne exposure of consumers and farm animals to DON.

PMID- 28761065
TI  - Probing helicity and the topological origins of helicity via non-local Hanbury
      Brown and Twiss correlations.
AB  - Quantum Hall edge modes are chiral while quantum spin Hall edge modes are
      helical. However, unlike chiral edge modes which always occur in topological
      systems, quasi-helical edge modes may arise in a trivial insulator too. These
      trivial quasi-helical edge modes are not topologically protected and therefore
      need to be distinguished from helical edge modes arising due to topological
      reasons. Earlier conductance measurements were used to identify these helical
      states, in this work we report on the advantage of using the non local shot noise
      as a probe for the helical nature of these states as also their topological or
      otherwise origin and compare them with chiral quantum Hall states. We see that in
      similar set-ups affected by same degree of disorder and inelastic scattering, non
      local shot noise "HBT" correlations can be positive for helical edge modes but
      are always negative for the chiral quantum Hall edge modes. Further, while
      trivial quasi-helical edge modes exhibit negative non-local"HBT" charge
      correlations, topological helical edge modes can show positive non-local "HBT"
      charge correlation. We also study the non-local spin correlations and Fano factor
      for clues as regards both the distinction between chirality/helicity as well as
      the topological/trivial dichotomy for helical edge modes.

PMID- 28761062
TI  - T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders.
AB  - We performed integrative analysis of genes associated with type 2 Diabetes
      Mellitus (T2DM) associated complications by automated text mining with manual
      curation and also gene expression analysis from Gene Expression Omnibus. They
      were analysed for pathogenic or protective role, trends, interaction with risk
      factors, Gene Ontology enrichment and tissue wise differential expression. The
      database T2DiACoD houses 650 genes, and 34 microRNAs associated with T2DM
      complications. Seven genes AGER, TNFRSF11B, CRK, PON1, ADIPOQ, CRP and NOS3 are
      associated with all 5 complications. Several genes are studied in multiple years
      in all complications with high proportion in cardiovascular (75.8%) and
      atherosclerosis (51.3%). T2DM Patients' skeletal muscle tissues showed high fold
      change in differentially expressed genes. Among the differentially expressed
      genes, VEGFA is associated with several complications of T2DM. A few genes ACE2,
      ADCYAP1, HDAC4, NCF1, NFE2L2, OSM, SMAD1, TGFB1, BDNF, SYVN1, TXNIP, CD36,
      CYP2J2, NLRP3 with details of protective role are catalogued. Obesity is clearly
      a dominant risk factor interacting with the genes of T2DM complications followed
      by inflammation, diet and stress to variable extents. This information emerging
      from the integrative approach used in this work could benefit further therapeutic
      approaches. The T2DiACoD is available at www.http://t2diacod.igib.res.in/ .

PMID- 28761066
TI  - Effects of chloride ions on corrosion of ductile iron and carbon steel in soil
      environments.
AB  - Chloride is reported to play a significant role in corrosion reactions, products
      and kinetics of ferrous metals. To enhance the understanding of the effects of
      soil environments, especially the saline soils with high levels of chloride, on
      the corrosion of ductile iron and carbon steel, a 3-month corrosion test was
      carried out by exposing ferrous metals to soils of six chloride concentrations.
      The surface morphology, rust compositions and corrosion kinetics were
      comprehensively studied by visual observation, scanning electron microscopy
      (SEM), X-Ray diffraction (XRD), weight loss, pit depth measurement, linear
      polarization and electrochemical impedance spectroscopy (EIS) measurements. It
      showed that chloride ions influenced the characteristics and compositions of rust
      layers by diverting and participating in corrosion reactions. alpha-FeOOH, gamma
      FeOOH and iron oxides were major corrosion products, while beta-Fe8O8(OH)8Cl1.35
      rather than beta-FeOOH was formed when high chloride concentrations were
      provided. Chloride also suppressed the decreasing of corrosion rates, whereas
      increased the difficulty in the diffusion process by thickening the rust layers
      and transforming the rust compositions. Carbon steel is more susceptible to
      chloride attacks than ductile iron. The corrosion kinetics of ductile iron and
      carbon steel corresponded with the probabilistic and bilinear model respectively.

PMID- 28761068
TI  - Prion strains depend on different endocytic routes for productive infection.
AB  - Prions are unconventional agents composed of misfolded prion protein that cause
      fatal neurodegenerative diseases in mammals. Prion strains induce specific
      neuropathological changes in selected brain areas. The mechanism of strain
      specific cell tropism is unknown. We hypothesised that prion strains rely on
      different endocytic routes to invade and replicate within their target cells.
      Using prion permissive cells, we determined how impairment of endocytosis affects
      productive infection by prion strains 22L and RML. We demonstrate that early and
      late stages of prion infection are differentially sensitive to perturbation of
      clathrin- and caveolin-mediated endocytosis. Manipulation of canonical endocytic
      pathways only slightly influenced prion uptake. However, blocking the same routes
      had drastic strain-specific consequences on the establishment of infection. Our
      data argue that prion strains use different endocytic pathways for infection and
      suggest that cell type-dependent differences in prion uptake could contribute to
      host cell tropism.

PMID- 28761067
TI  - Every-other-day feeding extends lifespan but fails to delay many symptoms of
      aging in mice.
AB  - Dietary restriction regimes extend lifespan in various animal models. Here we
      show that longevity in male C57BL/6J mice subjected to every-other-day feeding is
      associated with a delayed onset of neoplastic disease that naturally limits
      lifespan in these animals. We compare more than 200 phenotypes in over 20 tissues
      in aged animals fed with a lifelong every-other-day feeding or ad libitum access
      to food diet to determine whether molecular, cellular, physiological and
      histopathological aging features develop more slowly in every-other-day feeding
      mice than in controls. We also analyze the effects of every-other-day feeding on
      young mice on shorter-term every-other-day feeding or ad libitum to account for
      possible aging-independent restriction effects. Our large-scale analysis reveals
      overall only limited evidence for a retardation of the aging rate in every-other
      day feeding mice. The data indicate that every-other-day feeding-induced
      longevity is sufficiently explained by delays in life-limiting neoplastic
      disorders and is not associated with a more general slowing of the aging process
      in mice.Dietary restriction can extend the life of various model organisms. Here,
      Xie et al. show that intermittent periods of fasting achieved through every-other
      day feeding protect mice against neoplastic disease but do not broadly delay
      organismal aging in animals.

PMID- 28761069
TI  - Evidence for Treatment-by-Biomarker interaction for FDA-approved Oncology Drugs
      with Required Pharmacogenomic Biomarker Testing.
AB  - For oncology drugs that were approved by the US Food and Drug Administration
      (FDA) and required pharmacogenomic biomarker testing, we describe 1) the use of
      enrichment (biomarker-positive patients) and a randomized controlled design by
      pre-approval trials and 2) the treatment-by-biomarker interaction. From the 137
      drugs included in the FDA table, we selected the 22 oncology drugs with required
      genetic testing in their labels. These drugs corresponded to 35 approvals
      supported by 80 clinical studies included in the FDA medical officer reviews of
      efficacy. For two thirds of approvals (24/35, 69%), all clinical studies were
      restricted to biomarker-positive patients (enriched). Among the 11 remaining
      approvals with at least one non-enriched trial, for five approvals, the non
      enriched studies were non-randomized. The treatment-by-biomarker interaction was
      statistically significant for three approvals and missing for two. Among the six
      approvals with a non-enriched randomized controlled trial, three featured a
      statistically significant treatment-by-biomarker interaction (p < 0.10), for an
      enhanced treatment effect in the biomarker-positive subgroup. For two thirds of
      FDA approvals of anticancer agents, the requirement for predictive biomarker
      testing was based on clinical development restricted to biomarker-positive
      patients. We found only few cases with clinical evidence that biomarker-negative
      patients would not benefit from treatment.

PMID- 28761070
TI  - Homocysteine induces mitochondrial dysfunction involving the crosstalk between
      oxidative stress and mitochondrial pSTAT3 in rat ischemic brain.
AB  - Homocysteine (Hcy) has been shown to have a neurotoxic effect on ischemic brain
      cells; however, the underlying mechanisms remain incompletely understood. Here,
      we examined whether Hcy treatment influences mitochondria injury, oxidative
      stress, and mitochondrial STAT3 (mitoStat3) expression in rat ischemic brain. Our
      results demonstrated that Hcy treatment aggravated the damage of mitochondrial
      ultrastructure in the brain cortex and the dentate gyrus region of the
      hippocampus after focal cerebral ischemia. An elevated Hcy level was also
      accompanied by the significant inhibition of mitochondrial complex I-III
      enzymatic activities in addition to an increase in cytochrome c release. 8
      Hydroxy-2'-deoxyguanosine (8-OHdG) content and mitoStat3 protein phosphorylation
      level were increased in Hcy-treated animals, whereas AG490, a Jak2 inhibitor,
      inhibited mitoStat3 phosphorylation as well as 8-OHdG levels induced by Hcy. In
      vitro studies revealed that Hcy also markedly increased reactive oxygen species
      (ROS) and mitoStat3 levels. In addition, the inhibition of pSTAT3 reduced Hcy
      mediated increase in ROS levels, whereas quenching ROS using the ROS inhibitor
      glutathione ethyl ester inhibited Hcy-mediated pSTAT3 overactivation in Neuro2a
      cells. These findings suggest that the development of therapies that interfere
      with the ROS/pSTAT3 pathway may be helpful for treating cerebral infarction
      related diseases associated with Hcy.

PMID- 28761072
TI  - Chronic exposures to fungicide pyrimethanil: multi-organ effects on Italian tree
      frog (Hyla intermedia).
AB  - Amphibian habitats are easily contaminated by several pollutants, and in
      agricultural landscapes the likely exposure scenario is represented by
      pesticides. Many of these substances are known or suspected to act as endocrine
      disrupting chemicals (EDCs). The goal of the present study was to assess the
      effects of pyrimethanil, a common-used but also overlooked fungicide, on liver,
      kidney and gonadal differentiation of Hyla intermedia. Through a multi-organ
      evaluation, we demonstrated that a long term exposure to two environmentally
      relevant concentrations of pyrimethanil (5 and 50 ug/L) elicits a range of toxic
      responses. First we showed that pyrimethanil induces underdevelopment of ovaries
      and interferes with normal sexual differentiation, thus revealing the endocrine
      disruption potential of this fungicide. Moreover we revealed that all considered
      organs are seriously affected by this fungicide and both necrosis and apoptosis
      contribute to the histological response. This is the first report on the effects
      of pyrimethanil on gonads, liver and kidney histology of a non-model species and
      it demonstrates that the hazardous properties of this fungicide can result from
      several pathological processes affecting different key compartments of amphibian.

PMID- 28761073
TI  - Photo-enhanced Aqueous Solubilization of an Azo-compound.
AB  - We previously showed that disruption of intermolecular interactions, e.g., by
      lowering the molecular planarity and/or introducing bent structures, improves the
      aqueous solubility of compounds, and based upon that work, we hypothesized that
      azobenzene trans-to-cis photoswitching could also be utilized to enhance the
      aqueous solubility of compounds. Here, we demonstrate that UV/visible light
      irradiation can reversibly switch the aqueous solubilization of an anti-cancer
      candidate drug, a low-molecular-weight kinase inhibitor bearing an azobenzene
      moiety. The increase of solubilization associated with UV-induced trans-to-cis
      conversion may have clinical relevance, because the time-scale of thermal cis-to
      trans reversion at 37  degrees C is longer than that of oral absorption.

PMID- 28761071
TI  - PhosphoPredict: A bioinformatics tool for prediction of human kinase-specific
      phosphorylation substrates and sites by integrating heterogeneous feature
      selection.
AB  - Protein phosphorylation is a major form of post-translational modification (PTM)
      that regulates diverse cellular processes. In silico methods for phosphorylation
      site prediction can provide a useful and complementary strategy for complete
      phosphoproteome annotation. Here, we present a novel bioinformatics tool,
      PhosphoPredict, that combines protein sequence and functional features to predict
      kinase-specific substrates and their associated phosphorylation sites for 12
      human kinases and kinase families, including ATM, CDKs, GSK-3, MAPKs, PKA, PKB,
      PKC, and SRC. To elucidate critical determinants, we identified feature subsets
      that were most informative and relevant for predicting substrate specificity for
      each individual kinase family. Extensive benchmarking experiments based on both
      five-fold cross-validation and independent tests indicated that the performance
      of PhosphoPredict is competitive with that of several other popular prediction
      tools, including KinasePhos, PPSP, GPS, and Musite. We found that combining
      protein functional and sequence features significantly improves phosphorylation
      site prediction performance across all kinases. Application of PhosphoPredict to
      the entire human proteome identified 150 to 800 potential phosphorylation
      substrates for each of the 12 kinases or kinase families. PhosphoPredict
      significantly extends the bioinformatics portfolio for kinase function analysis
      and will facilitate high-throughput identification of kinase-specific
      phosphorylation sites, thereby contributing to both basic and translational
      research programs.

PMID- 28761074
TI  - Antidepressant-like effects and cognitive enhancement of Schisandra chinensis in
      chronic unpredictable mild stress mice and its related mechanism.
AB  - The aim of this study was to evaluate whether Schisandra chinensis extract (SCE)
      administration influences chronic unpredictable mild stress (CUMS)-induced
      depression and cognitive impairment, and explores underlying mechanisms. Sucrose
      preference test (SPT) and forced swimming test (FST) were used for assessing
      depressive symptoms, and Y-maze, Morris water maze were used for evaluating
      cognition processes. The results showed that CUMS (4 weeks) was effective in
      producing both depression and memory deficits in mice. Additionally, CUMS
      exposure significantly decreased brain derived neurotrophic factor (BDNF) levels
      in hippocampus as indicated by ELISA, immunohistochemistry and immunofluorescence
      assays, accompanied by down-regulated tyrosine kinase receptor B (TrkB)/cAMP
      response element binding protein (CREB)/extracellular signal-regulated kinase
      (ERK) and phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT)/ glycogen
      synthase kinase-3beta (GSK-3beta) signaling pathways. Chronic administration of
      SCE (600 or 1200 mg/kg, i.g.) significantly prevented all these CUMS-induced
      behavioral and biochemical alterations. It suggested that SCE could improve the
      depression-like emotional status and associated cognitive deficits in CUMS mice,
      which might be mediated by regulation of BDNF levels in hippocampus, as well as
      up-regulating of TrkB/CREB/ERK and PI3K/AKT/GSK-3beta pathways.

PMID- 28761075
TI  - Substrate and Fano Resonance Effects on the Reversal of Optical Binding Force
      between Plasmonic Cube Dimers.
AB  - The behavior of Fano resonance and the reversal of near field optical binding
      force of dimers over different substrates have not been studied so far. Notably,
      for particle clustering and aggregation, controlling the near filed binding force
      can be a key factor. In this work, we observe that if the closely located
      plasmonic cube homodimers over glass or high permittivity dielectric substrate
      are illuminated with plane wave, no reversal of lateral optical binding force
      occurs. But if we apply the same set-up over a plasmonic substrate, stable Fano
      resonance occurs along with the reversal of near field lateral binding force. It
      is observed that during such Fano resonance, stronger coupling occurs between the
      dimers and plasmonic substrate along with the strong enhancement of the substrate
      current. Such binding force reversals of plasmonic cube dimers have been
      explained based on the observed unusual behavior of optical Lorentz force during
      the induced stronger Fano resonance and the dipole-dipole resonance. Although
      previously reported reversals of near field optical binding forces were highly
      sensitive to particle size/shape (i.e. for heterodimers) and inter-particle
      distance, our configuration provides much relaxation of those parameters and
      hence could be verified experimentally with simpler experimental set-ups.

PMID- 28761076
TI  - "Embodied Body Language": an electrical neuroimaging study with emotional faces
      and bodies.
AB  - To date, most investigations in the field of affective neuroscience mainly
      focused on the processing of facial expressions, overlooking the exploration of
      emotional body language (EBL), its capability to express our emotions
      notwithstanding. Few electrophysiological studies investigated the time course
      and the neural correlates of EBL and the integration of face and body emotion
      related information. The aim of the present study was to investigate both the
      time course and the neural correlates underlying the integration of affective
      information conveyed by faces and bodies. We analysed EEG activities evoked
      during an expression matching task, requiring the judgment of emotional
      congruence between sequentially presented pairs of stimuli belonging to the same
      category (face-face or body-body), and between stimuli belonging to different
      categories (face-body or body-face). We focused on N400 time window and results
      showed that incongruent stimuli elicited a modulation of the N400 in all
      comparisons except for body-face condition. This modulation was mainly detected
      in the Middle Temporal Gyrus and within regions related to the mirror mechanism.
      More specifically, while the perception of incongruent facial expressions
      activates somatosensory-related representations, incongruent emotional body
      postures also require the activation of motor and premotor representations,
      suggesting a strict link between emotion and action.

PMID- 28761077
TI  - IL-4 as a Repurposed Biological Drug for Myocardial Infarction through
      Augmentation of Reparative Cardiac Macrophages: Proof-of-Concept Data in Mice.
AB  - Recent research has shown that reparative (alternatively activated or M2)
      macrophages play a role in repair of damaged tissues, including the infarcted
      hearts. Administration of IL-4 is known to augment M2 macrophages. This
      translational study thus aimed to investigate whether IL-4 administration is
      useful for the treatment of myocardial infarction. Long-acting IL-4 complex (IL
      4c; recombinant IL-4 mixed with anti-IL-4 monoclonal antibody as a stabilizer)
      was administered after coronary artery ligation in mice. It was observed that IL
      4c administration increased accumulation of CD206+F4/80+ M2-like macrophages
      predominantly in the injured myocardium, compared to the control. Sorted cardiac
      M2-like macrophages highly expressed wide-ranging tissue repair-related genes.
      Indeed, IL-4c administration enhanced cardiac function in association with
      reduced infarct size and enhanced tissue repair (strengthened connective tissue
      formation, improved microvascular formation and attenuated cardiomyocyte
      hypertrophy). Experiments using Trib1 -/- mice that had a depleted ability to
      develop M2 macrophages and other in-vitro studies supported that these IL-4
      mediated effects were induced via M2-like macrophages. On the other hand, when
      administered at Day 28 post-MI, the effects of IL-4c were diminished, suggesting
      a time-frame for IL-4 treatment to be effective. These data represent proof-of
      concept of efficacy of IL-4 treatment for acute myocardial infarction,
      encouraging its further development.

PMID- 28761079
TI  - Alterations in resting state connectivity along the autism trait continuum: a
      twin study.
AB  - Autism spectrum disorder (ASD) has been found to be associated with alterations
      in resting state (RS) functional connectivity, including areas forming the
      default mode network (DMN) and salience network (SN). However, insufficient
      control for confounding genetic and environmental influences and other
      methodological issues limit the generalizability of previous findings. Moreover,
      it has been hypothesized that ASD might be marked by early hyper-connectivity
      followed by later hypo-connectivity. To date, only a few studies have explicitly
      tested age-related influences on RS connectivity alterations in ASD. Using a
      within-twin pair design (N=150 twins; 8-23 years), we examined altered RS
      connectivity between core regions of the DMN and SN in relation to autistic trait
      severity and age in a sample of monozygotic (MZ) and dizygotic (DZ) twins showing
      typical development, ASD or other neurodevelopmental conditions. Connectivity
      between core regions of the SN was stronger in twins with higher autistic traits
      compared to their co-twins. This effect was significant both in the total sample
      and in MZ twins alone, highlighting the effect of non-shared environmental
      factors on the link between SN-connectivity and autistic traits. While this link
      was strongest in children, we did not identify differences between age groups for
      the SN. In contrast, connectivity between core hubs of the DMN was negatively
      correlated with autistic traits in adolescents and showed a similar trend in
      adults but not in children. The results support hypotheses of age-dependent
      altered RS connectivity in ASD, making altered SN and DMN connectivity promising
      candidate biomarkers for ASD.

PMID- 28761078
TI  - The complement system: a gateway to gene-environment interactions in
      schizophrenia pathogenesis.
AB  - The pathogenesis of schizophrenia is considered to be multi-factorial, with
      likely gene-environment interactions (GEI). Genetic and environmental risk
      factors are being identified with increasing frequency, yet their very number
      vastly increases the scope of possible GEI, making it difficult to identify them
      with certainty. Accumulating evidence suggests a dysregulated complement pathway
      among the pathogenic processes of schizophrenia. The complement pathway mediates
      innate and acquired immunity, and its activation drives the removal of damaged
      cells, autoantigens and environmentally derived antigens. Abnormalities in
      complement functions occur in many infectious and autoimmune disorders that have
      been linked to schizophrenia. Many older reports indicate altered serum
      complement activity in schizophrenia, though the data are inconclusive.
      Compellingly, recent genome-wide association studies suggest repeat polymorphisms
      incorporating the complement 4A (C4A) and 4B (C4B) genes as risk factors for
      schizophrenia. The C4A/C4B genetic associations have re-ignited interest not only
      in inflammation-related models for schizophrenia pathogenesis, but also in
      neurodevelopmental theories, because rodent models indicate a role for complement
      proteins in synaptic pruning and neurodevelopment. Thus, the complement system
      could be used as one of the 'staging posts' for a variety of focused studies of
      schizophrenia pathogenesis. They include GEI studies of the C4A/C4B repeat
      polymorphisms in relation to inflammation-related or infectious processes, animal
      model studies and tests of hypotheses linked to autoimmune diseases that can co
      segregate with schizophrenia. If they can be replicated, such studies would
      vastly improve our understanding of pathogenic processes in schizophrenia through
      GEI analyses and open new avenues for therapy.

PMID- 28761080
TI  - Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor
      dependent manner.
AB  - Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where
      they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus
      of the stria terminalis (BNST), a major subdivision of the extended amygdala that
      has been proposed to regulate responses to anxiogenic environments in humans and
      rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT
      innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains
      unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in
      the dBNST reduces anxiety in a highly anxiogenic environment. Further analysis
      revealed that optogenetic inhibition of 5-HT inputs into the dBNST increases
      anxiety in a less anxiogenic environment. We found that 5-HT predominantly
      hyperpolarizes dBNST neurons, reducing their activity in a manner that can be
      blocked by a 5-HT1A antagonist. Finally, we demonstrate that activation of 5-HT1A
      receptors in the dBNST is necessary for the anxiolytic effect observed following
      optogenetic stimulation of 5-HT inputs into the dBNST. These data reveal that 5
      HT release in the dBNST modulates anxiety-like behavior via 5-HT1A receptors
      under naturalistic conditions.

PMID- 28761081
TI  - A neurogenetic model for the study of schizophrenia spectrum disorders: the
      International 22q11.2 Deletion Syndrome Brain Behavior Consortium.
AB  - Rare copy number variants contribute significantly to the risk for schizophrenia,
      with the 22q11.2 locus consistently implicated. Individuals with the 22q11.2
      deletion syndrome (22q11DS) have an estimated 25-fold increased risk for
      schizophrenia spectrum disorders, compared to individuals in the general
      population. The International 22q11DS Brain Behavior Consortium is examining this
      highly informative neurogenetic syndrome phenotypically and genomically. Here we
      detail the procedures of the effort to characterize the neuropsychiatric and
      neurobehavioral phenotypes associated with 22q11DS, focusing on schizophrenia and
      subthreshold expression of psychosis. The genomic approach includes a combination
      of whole-genome sequencing and genome-wide microarray technologies, allowing the
      investigation of all possible DNA variation and gene pathways influencing the
      schizophrenia-relevant phenotypic expression. A phenotypically rich data set
      provides a psychiatrically well-characterized sample of unprecedented size
      (n=1616) that informs the neurobehavioral developmental course of 22q11DS. This
      combined set of phenotypic and genomic data will enable hypothesis testing to
      elucidate the mechanisms underlying the pathogenesis of schizophrenia spectrum
      disorders.

PMID- 28761082
TI  - Selective activation of parvalbumin interneurons prevents stress-induced synapse
      loss and perceptual defects.
AB  - Stress, a prevalent experience in modern society, is a major risk factor for many
      psychiatric disorders. Although sensorimotor abnormalities are often present in
      these disorders, little is known about how stress affects the sensory cortex.
      Combining behavioral analyses with in vivo synaptic imaging, we show that
      stressful experiences lead to progressive, clustered loss of dendritic spines
      along the apical dendrites of layer (L) 5 pyramidal neurons (PNs) in the mouse
      barrel cortex, and such spine loss closely associates with deteriorated
      performance in a whisker-dependent texture discrimination task. Furthermore, the
      activity of parvalbumin-expressing inhibitory interneurons (PV+ INs) decreases in
      the stressed mouse due to reduced excitability of these neurons. Importantly,
      both behavioral defects and structural changes of L5 PNs are prevented by
      selective pharmacogenetic activation of PV+INs in the barrel cortex during
      stress. Finally, stressed mice raised under environmental enrichment (EE)
      maintain normal activation of PV+ INs, normal texture discrimination, and L5 PN
      spine dynamics similar to unstressed EE mice. Our findings suggest that the PV+
      inhibitory circuit is crucial for normal synaptic dynamics in the mouse barrel
      cortex and sensory function. Pharmacological, pharmacogenetic and environmental
      approaches to prevent stress-induced maladaptive behaviors and synaptic
      malfunctions converge on the regulation of PV+ IN activity, pointing to a
      potential therapeutic target for stress-related disorders.

PMID- 28761083
TI  - Revealing the complex genetic architecture of obsessive-compulsive disorder using
      meta-analysis.
AB  - Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs)
      have been published by independent OCD consortia, the International Obsessive
      Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD
      Collaborative Genetics Association Study (OCGAS), but many of the top-ranked
      signals were supported in only one study. We therefore conducted a meta-analysis
      from the two consortia, investigating a total of 2688 individuals of European
      ancestry with OCD and 7037 genomically matched controls. No single-nucleotide
      polymorphisms (SNPs) reached genome-wide significance. However, in comparison
      with the two individual GWASs, the distribution of P-values shifted toward
      significance. The top haplotypic blocks were tagged with rs4733767 (P=7.1 * 10-7;
      odds ratio (OR)=1.21; confidence interval (CI): 1.12-1.31, CASC8/CASC11),
      rs1030757 (P=1.1 * 10-6; OR=1.18; CI: 1.10-1.26, GRID2) and rs12504244 (P=1.6 *
      10-6; OR=1.18; CI: 1.11-1.27, KIT). Variants located in or near the genes ASB13,
      RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2 and CDH20, identified in linkage peaks and the
      original GWASs, were among the top signals. Polygenic risk scores for each
      individual study predicted case-control status in the other by explaining 0.9%
      (P=0.003) and 0.3% (P=0.0009) of the phenotypic variance in OCGAS and the
      European IOCDF-GC target samples, respectively. The common SNP heritability in
      the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e.=0.04).
      Strikingly, ~65% of the SNP-based heritability in the OCGAS sample was accounted
      for by SNPs with minor allele frequencies of ?40%. This joint analysis
      constituting the largest single OCD genome-wide study to date represents a major
      integrative step in elucidating the genetic causes of OCD.

PMID- 28761084
TI  - Single vector non-leaky gene expression system for Drosophila melanogaster.
AB  - An ideal transgenic gene expression system is inducible, non-leaky, and well
      tolerated by the target organism. While the former has been satisfactorily
      realized, leakiness and heavy physiological burden imposed by the existing
      systems are still prominent hurdles in their successful implementation. Here we
      describe a new system for non-leaky expression of transgenes in Drosophila.
      PRExpress is based on a single transgenic construct built from endogenous
      components, the inducible hsp70 promoter and a multimerized copy of a Polycomb
      response element (PRE) controlled by epigenetic chromatin regulators of the
      Polycomb group. We show that this system is non-leaky, rapidly and strongly
      inducible, and reversible. To make the application of PRExpress user-friendly, we
      deliver the construct via site-specific integration.

PMID- 28761085
TI  - Corn-like, recoverable gamma-Fe2O3@SiO2@TiO2 photocatalyst induced by magnetic
      dipole interactions.
AB  - Corn-like, gamma-Fe2O3@SiO2@TiO2 core/shell heterostructures were synthesized by
      a modified solvothermal reduction combined with a sol-gel method. SiO2 shells
      were first deposited on monodisperse Fe3O4 microspheres by a sol-gel method.
      Fe3O4@SiO2@TiO2 corn-like heterostructures were then obtained by sequential TiO2
      coating, during which the magnetic dipolar interactions induced the anisotropic
      self-assembly process. After annealing at 350  degrees C, the crystalized TiO2
      enhanced photocatalytic activity, while Fe3O4 was converted to gamma-Fe2O3. The
      corn-like gamma-Fe2O3@SiO2@TiO2 photocatalyst can be recycled and reused by
      magnet extraction. Despite the photocatalytic activity decreased with each cycle,
      it can be completely recovered by moderate heating at 200  degrees C.

PMID- 28761086
TI  - Serotonin hormonally regulates lacrimal gland secretory function via the
      serotonin type 3a receptor.
AB  - Tears are extracellular fluid secreted from the lacrimal gland (LG). Tears
      consist of a dynamic tri-layered film composed of secretions from the LG,
      Meibomian gland, and conjunctival goblet cells. The LG secretes the aqueous
      component of the tear, the Meibomian gland secretes the lipid component, and
      conjunctival goblet cells secrete mucin. The regulation of LG activity via the
      autonomic nervous system has been recognized as fundamental to maintaining
      aqueous tear flow. Here, we describe the role of a hormone, peripheral serotonin,
      in tear secretion. We found that blood serotonin concentration, changed by
      feeding a diet deprived of the serotonin precursor tryptophan, correlated with
      tear secretion, and that a sustained decrease in serotonin resulted in LG atrophy
      and autophagy. The combination of a decrease in serotonin with the interruption
      of autonomic neural stimuli to the LG preceded these alterations. Furthermore, we
      found that the serotonin type 3a receptor expressed in LG acinar cells is
      involved in tear secretion via intracellular calcium mobilization. Our findings
      demonstrate that hormonal regulation by serotonin, in cooperation with the
      autonomic nervous system, regulates tear secretion.

PMID- 28761087
TI  - Ethylene, an early marker of systemic inflammation in humans.
AB  - Ethylene is a major plant hormone mediating developmental processes and stress
      responses to stimuli such as infection. We show here that ethylene is also
      produced during systemic inflammation in humans and is released in exhaled
      breath. Traces of ethylene were detected by laser spectroscopy both in vitro in
      isolated blood leukocytes exposed to bacterial lipopolysaccharide (LPS) as well
      as in vivo following LPS administration in healthy volunteers. Exposure to LPS
      triggers formation of ethylene as a product of lipid peroxidation induced by the
      respiratory burst. In humans, ethylene was detected prior to the increase of
      blood levels of inflammatory cytokines and stress-related hormones. Our results
      highlight that ethylene release is an early and integral component of in vivo
      lipid peroxidation with important clinical implications as a breath biomarker of
      bacterial infection.

PMID- 28761088
TI  - Shift of EMT gradient in 3D spheroid MSCs for activation of mesenchymal niche
      function.
AB  - Despite the wide use of mesenchymal stromal cells (MSCs) for paracrine support in
      clinical trials, their variable and heterogeneous supporting activity pose major
      challenges. While three-dimensional (3D) MSC cultures are emerging as alternative
      approaches, key changes in cellular characteristics during 3D-spheroid formation
      remain unclear. Here, we show that MSCs in 3D spheroids undergo further
      progression towards the epithelial-mesenchymal transition (EMT), driven by
      upregulation of EMT-promoting microRNAs and suppression of EMT-inhibitory miRNAs.
      The shift of EMT in MSCs is associated with widespread histone modifications
      mimicking the epigenetic reprogramming towards enhanced chromatin dynamics and
      stem cell-like properties, but without changes in their surface phenotype.
      Notably, these molecular shifts towards EMT in 3D MSCs caused enhanced stem cell
      niche activity, resulting in higher stimulation of hematopoietic progenitor self
      renewal and cancer stem cell metastasis. Moreover, miRNA-mediated induction of
      EMT in 2D MSCs were sufficient to mimic the enhanced niche activity of 3D
      spheroid MSCs. Thus, the molecular hierarchy in the EMT gradient among
      phenotypically indistinguishable MSCs revealed the previously unrecognized
      functional parameters in MSCs, and the EMT-enhanced "naive" mesenchymal state
      represents an 'activated mesenchymal niche' in 3D spheroid MSCs.

PMID- 28761089
TI  - Membrane Perfusion of Hydrophobic Substances Around Channels Embedded in the
      Contact Bubble Bilayer.
AB  - In fluidic biomembranes, lipids and membrane proteins diffuse restlessly, and
      lipid compositions change steadily. To mimic dynamic behavior of the
      biomembranes, a method for introducing rapid changes in the constituents in the
      lipid bilayer was developed. In contact bubble bilayers (CBB), as a water-in-oil
      droplet bilayer system, the bilayer hydrophobic interior is contiguous with the
      bulk oil phase. Making use of this geometrical feature as an access route,
      hydrophobic substances were administered into the bilayer. Polytheonamide B, a
      cytotoxic hydrophobic peptide, was applied, and oriented incorporation and
      relevant single-channel current recordings were enabled. Nystatin was pre-loaded
      in the CBB, and sterol perfusion exhibited slow development of the macroscopic
      current. On the contrary, the reconstituted KcsA potassium channels immediately
      attenuate the channel activity when cholesterol was applied. This oil-phase route
      in the CBB allows rapid perfusion of hydrophobic substances around the bilayer
      embedded channels during continuous recordings of channel currents.

PMID- 28761090
TI  - Restricted regions of enhanced growth of Antarctic krill in the circumpolar
      Southern Ocean.
AB  - Food webs in high-latitude oceans are dominated by relatively few species. Future
      ocean and sea-ice changes affecting the distribution of such species will impact
      the structure and functioning of whole ecosystems. Antarctic krill (Euphausia
      superba) is a key species in Southern Ocean food webs, but there is little
      understanding of the factors influencing its success throughout much of the
      ocean. The capacity of a habitat to maintain growth will be crucial and here we
      use an empirical relationship of growth rate to assess seasonal spatial
      variability. Over much of the ocean, potential for growth is limited, with three
      restricted oceanic regions where seasonal conditions permit high growth rates,
      and only a few areas around the Scotia Sea and Antarctic Peninsula suitable for
      growth of the largest krill (>60 mm). Our study demonstrates that projections of
      impacts of future change need to account for spatial and seasonal variability of
      key ecological processes within ocean ecosystems.

PMID- 28761091
TI  - A novel pharmacodynamic assay to evaluate the effects of crystallization
      inhibitors on calcium phosphate crystallization in human plasma.
AB  - Cardiovascular calcification (CVC) is a progressive complication of chronic
      kidney disease and a predictor of CV events and mortality. The use of biomarkers
      to predict CV risk and activities of potential or current treatment drugs in
      these patients could have a crucial impact on therapeutic approaches. Our aim was
      to develop a novel assay for measurement of the rate of calcium phosphate
      crystallization in human plasma and provide a tool to evaluate the effects of
      crystallization inhibitors. The efficacy of inhibitors was determined by adding
      inhibitory compounds (polyphosphates, fetuin-A, sodium thiosulfate or citrate) to
      control samples. The assay was additionally validated for SNF472, an experimental
      formulation of phytate being developed for the treatment of calciphylaxis and CVC
      in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The
      method was repeatable and reproducible. The plasma crystallization rate was
      reduced up to 80% in a concentration-dependent manner following treatment with
      inhibitors in vitro, among which SNF472 was the most potent. This method appears
      beneficial in evaluating and discriminating between inhibitory activities of
      compounds such as polyphosphates on calcium phosphate crystallization, which
      present a novel therapeutic approach to treat CVC in ESRD patients.

PMID- 28761092
TI  - Early life-history predator-prey reversal in two cyprinid fishes.
AB  - Predator-prey relationships are often perceived simply as a situation in which a
      predator enhances its own fitness while reducing the fitness of its prey.
      However, this relationship may become reversed when the prey feeds on the
      juvenile predator stages. We investigated this phenomenon in a model asp
      (Leuciscus aspius; predator)-bleak (Alburnus alburnus; prey) relationship. The
      adhesive asp eggs are available for bleak predation after a spawning event for
      only tens of seconds before they adhere to the stones, where bleak do not forage.
      Gut content analysis demonstrated that eggs were utilized in high quantities,
      especially in the spawning peak of the asp reproductive season. Furthermore,
      using underwater video, we recorded the bleak feeding efficiency on naturally
      drifting asp eggs as the percentage of eggs eaten. Within the 40 cm egg
      trajectory captured by our cameras, total egg mortality was 21.2 +/- 2.2% on
      average. The highest survival chances occurred among eggs drifting in
      aggregations, since the short drifting distance together with their aggregated
      distribution satiated bleak and part of the egg aggregation could attach to the
      spawning ground. This study emphasizes the potential efficiency of predator egg
      utilization by prey, which may have further consequences in predator-prey
      dynamics.

PMID- 28761094
TI  - Xylapeptide A, an Antibacterial Cyclopentapeptide with an Uncommon L-Pipecolinic
      Acid Moiety from the Associated Fungus Xylaria sp. (GDG-102).
AB  - Two new cyclopentapeptides, xylapeptide A (1) with an uncommon L-pipecolinic acid
      moiety, and xylapeptide B (2) having a common L-proline residue were identified
      from an associated fungus Xylaria sp. isolated from the Chinese medicinal plant
      Sophora tonkinensis. Their planar structures were elucidated by a comprehensive
      analysis of NMR and MS spectroscopic spectra. The absolute configurations were
      determined by Marfey's method and single-crystal X-ray diffraction (Cu Kalpha)
      analysis. Xylapeptide A (1) is the first example of cyclopentapeptide with L-Pip
      of terrestrial origin and showed strong antibacterial activity against Bacillus
      subtilis and B. cereus with MIC value of 12.5 MUg/mL.

PMID- 28761093
TI  - Combined serum levels of multiple proteins in tPA-BDNF pathway may aid the
      diagnosis of five mental disorders.
AB  - Mental disorders are severe, disabling conditions with unknown etiology and are
      commonly misdiagnosed when clinical symptomology criteria are solely used. Our
      previous work indicated that combination of serum levels of multiple proteins in
      tissue plasminogen activator (tPA)-brain-derived neurotrophic factor (BDNF)
      pathway improved accuracy of diagnosis of major depressive disorder (MDD). Here,
      we measured serum levels of tPA, plasminogen activator inhibitor-1 (PAI-1), BDNF,
      precursor-BDNF (proBDNF), tropomyosin-related kinase B (TrkB) and neurotrophin
      receptor p75 (p75NTR) in patients with paranoid schizophrenia (SZ, n = 34), MDD
      (n = 30), bipolar mania (BM, n = 30), bipolar depression (BD, n = 22), panic
      disorder (PD, n = 30), and healthy controls (HCs, n = 30) by Enzyme-linked
      immunosorbent assay kits. We used receiver operating characteristic (ROC) curve
      to analyze diagnostic potential of these proteins. We found, compared with HCs,
      that serum tPA and proBDNF were lower in SZ, BM and BD; TrkB was lower in SZ and
      BD; and p75NTR was declined in SZ and BM. ROC analysis showed that combined serum
      level of tPA, PAI-1, BDNF, proBDNF, TrkB and p75NTR was better than any single
      protein in accuracy of diagnosis and differentiation, suggesting that the
      combination of multiple serum proteins levels in tPA-BDNF pathway may have a
      potential for a diagnostic panel in mental disorders.

PMID- 28761095
TI  - Associations between subjective well-being and subcortical brain volumes.
AB  - To study the underpinnings of individual differences in subjective well-being
      (SWB), we tested for associations of SWB with subcortical brain volumes in a
      dataset of 724 twins and siblings. For significant SWB-brain associations we
      probed for causal pathways using Mendelian Randomization (MR) and estimated
      genetic and environmental contributions from twin modeling. Another independent
      measure of genetic correlation was obtained from linkage disequilibrium (LD)
      score regression on published genome-wide association summary statistics. Our
      results indicated associations of SWB with hippocampal volumes but not with
      volumes of the basal ganglia, thalamus, amygdala, or nucleus accumbens. The SWB
      hippocampus relations were nonlinear and characterized by lower SWB in subjects
      with relatively smaller hippocampal volumes compared to subjects with medium and
      higher hippocampal volumes. MR provided no evidence for an SWB to hippocampal
      volume or hippocampal volume to SWB pathway. This was in line with twin modeling
      and LD-score regression results which indicated non-significant genetic
      correlations. We conclude that low SWB is associated with smaller hippocampal
      volume, but that genes are not very important in this relationship. Instead other
      etiological factors, such as exposure to stress and stress hormones, may exert
      detrimental effects on SWB and the hippocampus to bring about the observed
      association.

PMID- 28761096
TI  - Electrophysiological evidence for pre-attention information processing
      improvement in patients with central hemiplegic after peripheral nerve rewiring:
      a pilot study.
AB  - Central neurologic injury (CNI) causes dysfunctions not only in limbs but also in
      cognitive ability. We applied a novel peripheral nerve rewiring (PNR) surgical
      procedure to restore limb function. Here, we conducted a prospective study to
      develop estimates for the extent of preattentive processes to cognitive function
      changes in CNI patients after PNR. Auditory mismatch negativity (MMN) was
      measured in CNI patients who received the PNR surgery plus conventional
      rehabilitation treatment. During the 2-year follow-up, the MMN was enhanced with
      increased amplitude in the PNR plus rehabilitation group compared to the
      rehabilitation-only group as the experiment progressed, and progressive
      improvement in behavioural examination tests was also observed. Furthermore, we
      found a significant correlation between the changes in Fugl-Meyer assessment
      scale scores and in MMN amplitudes. These results suggested that PNR could affect
      the efficiency of pre-attention information processing synchronously with the
      recovery of motor function in the paralyzed arm of the in chronic CNI patients.
      Such electroencephalographic measures might provide a biological approach with
      which to distinguish patient subgroups after surgery, and the change in MMN may
      serve as an objective auxiliary index, indicating the degree of motor recovery
      and brain cognitive function.

PMID- 28761098
TI  - Seismological evidence for a localized mushy zone at the Earth's inner core
      boundary.
AB  - Although existence of a mushy zone in the Earth's inner core has been
      hypothesized several decades ago, no seismic evidence has ever been reported.
      Based on waveform modeling of seismic compressional waves that are reflected off
      the Earth's inner core boundary, here we present seismic evidence for a localized
      4-8 km thick zone across the inner core boundary beneath southwest Okhotsk Sea
      with seismic properties intermediate between those of the inner and outer core
      and of a mushy zone. Such a localized mushy zone is found to be surrounded by a
      sharp inner core boundary nearby. These seismic results suggest that, in the
      current thermo-compositional state of the Earth's core, the outer core
      composition is close to eutectic in most regions resulting in a sharp inner core
      boundary, but deviation from the eutectic composition exists in some localized
      regions resulting in a mushy zone with a thickness of 4-8 km.The existence of a
      mushy zone in the Earth's inner core has been suggested, but has remained
      unproven. Here, the authors have discovered a 4-8 km thick mushy zone at the
      inner core boundary beneath the Okhotsk Sea, indicating that there may be more
      localized mushy zones at the inner core boundary.

PMID- 28761097
TI  - Structures and transport dynamics of a Campylobacter jejuni multidrug efflux
      pump.
AB  - Resistance-nodulation-cell division efflux pumps are integral membrane proteins
      that catalyze the export of substrates across cell membranes. Within the
      hydrophobe-amphiphile efflux subfamily, these resistance-nodulation-cell division
      proteins largely form trimeric efflux pumps. The drug efflux process has been
      proposed to entail a synchronized motion between subunits of the trimer to
      advance the transport cycle, leading to the extrusion of drug molecules. Here we
      use X-ray crystallography and single-molecule fluorescence resonance energy
      transfer imaging to elucidate the structures and functional dynamics of the
      Campylobacter jejuni CmeB multidrug efflux pump. We find that the CmeB trimer
      displays a very unique conformation. A direct observation of transport dynamics
      in individual CmeB trimers embedded in membrane vesicles indicates that each CmeB
      subunit undergoes conformational transitions uncoordinated and independent of
      each other. On the basis of our findings and analyses, we propose a model for
      transport mechanism where CmeB protomers function independently within the
      trimer.Multidrug efflux pumps significantly contribute for bacteria resistance to
      antibiotics. Here the authors present the structure of Campylobacter jejuni CmeB
      pump combined with functional FRET assays to propose a transport mechanism where
      each CmeB protomers is functionally independent from the trimer.

PMID- 28761100
TI  - Charge carrier localised in zero-dimensional (CH3NH3)3Bi2I9 clusters.
AB  - A metal-organic hybrid perovskite (CH3NH3PbI3) with three-dimensional framework
      of metal-halide octahedra has been reported as a low-cost, solution-processable
      absorber for a thin-film solar cell with a power-conversion efficiency over 20%.
      Low-dimensional layered perovskites with metal halide slabs separated by the
      insulating organic layers are reported to show higher stability, but the
      efficiencies of the solar cells are limited by the confinement of excitons. In
      order to explore the confinement and transport of excitons in zero-dimensional
      metal-organic hybrid materials, a highly orientated film of (CH3NH3)3Bi2I9 with
      nanometre-sized core clusters of Bi2I93- surrounded by insulating CH3NH3+ was
      prepared via solution processing. The (CH3NH3)3Bi2I9 film shows highly
      anisotropic photoluminescence emission and excitation due to the large proportion
      of localised excitons coupled with delocalised excitons from intercluster energy
      transfer. The abrupt increase in photoluminescence quantum yield at excitation
      energy above twice band gap could indicate a quantum cutting due to the low
      dimensionality.Understanding the confinement and transport of excitons in low
      dimensional systems will aid the development of next generation photovoltaics.
      Via photophysical studies Ni et al. observe 'quantum cutting' in 0D metal-organic
      hybrid materials based on methylammonium bismuth halide (CH3NH3)3Bi2I9.

PMID- 28761099
TI  - Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor.
AB  - Respiratory syncytial virus is a major cause of acute lower respiratory tract
      infection in young children, immunocompromised adults, and the elderly.
      Intervention with small-molecule antivirals specific for respiratory syncytial
      virus presents an important therapeutic opportunity, but no such compounds are
      approved today. Here we report the structure of JNJ-53718678 bound to respiratory
      syncytial virus fusion (F) protein in its prefusion conformation, and we show
      that the potent nanomolar activity of JNJ-53718678, as well as the preliminary
      structure-activity relationship and the pharmaceutical optimization strategy of
      the series, are consistent with the binding mode of JNJ-53718678 and other
      respiratory syncytial virus fusion inhibitors. Oral treatment of neonatal lambs
      with JNJ-53718678, or with an equally active close analog, efficiently inhibits
      established acute lower respiratory tract infection in the animals, even when
      treatment is delayed until external signs of respiratory syncytial virus illness
      have become visible. Together, these data suggest that JNJ-53718678 is a
      promising candidate for further development as a potential therapeutic in
      patients at risk to develop respiratory syncytial virus acute lower respiratory
      tract infection.Respiratory syncytial virus causes lung infections in children,
      immunocompromised adults, and in the elderly. Here the authors show that a
      chemical inhibitor to a viral fusion protein is effective in reducing viral titre
      and ameliorating infection in rodents and neonatal lambs.

PMID- 28761102
TI  - Approach of automatic 3D geological mapping: the case of the Kovdor phoscorite
      carbonatite complex, NW Russia.
AB  - We have developed an approach for automatic 3D geological mapping based on
      conversion of chemical composition of rocks to mineral composition by logical
      computation. It allows to calculate mineral composition based on bulk rock
      chemistry, interpolate the mineral composition in the same way as chemical
      composition, and, finally, build a 3D geological model. The approach was
      developed for the Kovdor phoscorite-carbonatite complex containing the Kovdor
      baddeleyite-apatite-magnetite deposit. We used 4 bulk rock chemistry analyses -
      Femagn, P2O5, CO2 and SiO2. We used four techniques for prediction of rock types 
      calculation of normative mineral compositions (norms), multiple regression,
      artificial neural network and developed by logical evaluation. The two latter
      became the best. As a result, we distinguished 14 types of phoscorites
      (forsterite-apatite-magnetite-carbonate rock), carbonatite and host rocks. The
      results show good convergence with our petrographical studies of the deposit, and
      recent manually built maps. The proposed approach can be used as a tool of a
      deposit genesis reconstruction and preliminary geometallurgical modelling.

PMID- 28761101
TI  - A short D-enantiomeric antimicrobial peptide with potent immunomodulatory and
      antibiofilm activity against multidrug-resistant Pseudomonas aeruginosa and
      Acinetobacter baumannii.
AB  - Antimicrobial peptides (AMPs) represent a promising therapeutic alternative for
      the treatment of antibiotic-resistant bacterial infections. The present study
      investigates the antimicrobial activity of new, rationally-designed derivatives
      of a short alpha-helical peptide, RR. From the peptides designed, RR4 and its D
      enantiomer, D-RR4, emerged as the most potent analogues with a more than 32-fold
      improvement in antimicrobial activity observed against multidrug-resistant
      strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Remarkably, D-RR4
      demonstrated potent activity against colistin-resistant strains of P. aeruginosa
      (isolated from cystic fibrosis patients) indicating a potential therapeutic
      advantage of this peptide over several AMPs. In contrast to many natural AMPs, D
      RR4 retained its activity under challenging physiological conditions (high salts,
      serum, and acidic pH). Furthermore, D-RR4 was more capable of disrupting P.
      aeruginosa and A. baumannii biofilms when compared to conventional antibiotics.
      Of note, D-RR4 was able to bind to lipopolysaccharide to reduce the endotoxin
      induced proinflammatory cytokine response in macrophages. Finally, D-RR4
      protected Caenorhabditis elegans from lethal infections of P. aeruginosa and A.
      baumannii and enhanced the activity of colistin in vivo against colistin
      resistant P. aeruginosa.

PMID- 28761103
TI  - Towards Picogram Detection of Superparamagnetic Iron-Oxide Particles Using a
      Gradiometric Receive Coil.
AB  - Superparamagnetic iron-oxide nanoparticles can be used in medical applications
      like vascular or targeted imaging. Magnetic particle imaging (MPI) is a promising
      tomographic imaging technique that allows visualizing the 3D nanoparticle
      distribution concentration in a non-invasive manner. The two main strengths of
      MPI are high temporal resolution and high sensitivity. While the first has been
      proven in the assessment of dynamic processes like cardiac imaging, it is unknown
      how far the detection limit of MPI can be lowered. Within this work, we will
      present a highly sensitive gradiometric receive-coil unit combined with a noise
      matching network tailored for the imaging of mice. The setup is capable of
      detecting 5 ng of iron in-vitro with an acquisition time of 2.14 sec. In terms of
      iron concentration we are able to detect 156 MUg/L marking the lowest value that
      has been reported for an MPI scanner so far. In-vivo MPI mouse images of a 512 ng
      bolus and a 21.5 ms acquisition time allow for capturing the flow of an
      intravenously injected tracer through the heart of a mouse. Since it has been
      rather difficult to compare detection limits across MPI publications we propose
      guidelines to improve the comparability of future MPI studies.

PMID- 28761104
TI  - Microfluidic sorting of intrinsically magnetic cells under visual control.
AB  - Magnetic cell sorting provides a valuable complementary mechanism to fluorescent
      techniques, especially if its parameters can be fine-tuned. In addition, there
      has recently been growing interest in studying naturally occurring magnetic cells
      and genetic engineering of cells to render them magnetic in order to control
      molecular processes via magnetic fields. For such approaches, contamination-free
      magnetic separation is an essential capability. We here present a robust and
      tunable microfluidic sorting system in which magnetic gradients of up to 1700 T/m
      can be applied to cells flowing through a sorting channel by reversible
      magnetization of ferrofluids. Visual control of the sorting process allowed us to
      optimize sorting efficiencies for a large range of sizes and magnetic moments of
      cells. Using automated quantification based on imaging of fluorescent markers, we
      showed that macrophages containing phagocytosed magnetic nanoparticles, with
      cellular magnetic dipole moments on the order of 10 fAm2, could be sorted with an
      efficiency of 90 +/- 1%. Furthermore, we successfully sorted intrinsically
      magnetic magnetotactic bacteria with magnetic moments of 0.1 fAm2. In distinction
      to column-based magnetic sorting devices, microfluidic systems can prevent sample
      contact with superparamagnetic material. This ensures contamination-free
      separation of naturally occurring or bioengineered magnetic cells and is
      essential for downstream characterization of their properties.

PMID- 28761105
TI  - Rapid ILs-polishing Processes Toward Flexible Nanostructured Paper with Dually
      High Transparency and Haze.
AB  - Biodegradable highly nanostructured paper has received great interest in past
      years due to its excellent optical properties which facilitate its wide
      applications in green flexible electronics and devices. However, energy and/or
      time-consuming procedure during the process of fabricating most nanostructured
      transparent paper are presently the main obstacle to their scalable production.
      In this work, we demonstrated a novel nanostructured paper with dually high
      transparency (~91%) and high haze (~89%) that was directly fabricated from
      original paper with rapid ILs-polishing processes. The whole fabricating time
      only requires 10 min. Compared to the previously reported nanopaper made of the
      isolated cellulose nanofibers by pure mechanical and/or chemical approaches, this
      work presented herein is devoted to use green ILs to polish directly the
      micrometer-sized fibrous paper into the nanostructured paper. This new method
      brings a rapid fabrication of transparent nanostructured paper while also
      retaining dual intriguing properties both in optical transmittance and haze. This
      work is capable of fabricating next-generation flexible and highly transparent
      and haze paper by a high-speed roll-to-roll manufacturing process with a much
      lower cost.

PMID- 28761106
TI  - Overall process of using a valerate-dominant sludge hydrolysate to produce high
      quality polyhydroxyalkanoates (PHA) in a mixed culture.
AB  - The overall process of polyhydroxyalkanoates (PHA) production in a mixed culture
      fed by thermophilic fermented valerate-dominant sludge hydrolysate with high
      level soluble organics (proteins and carbohydrates) and nutrients (nitrogen and
      phosphorus) was investigated in this study. The valerate-dominant hydrolysate was
      fed to enrich a PHA culture with an increasing concentration, and the enriched
      culture displayed a strong PHA-producing capacity under feast-famine conditions.
      Valerate in the feedstock was preferentially utilized over acetate and butyrate,
      and its uptake correlated with the production of 3-hydroxyvalerate (3HV) and 3
      hydroxy-2-methylvalerate (3H2MV). The maximum PHA content (42.31%) was highest to
      date in a mixed culture with complex feedstock, and the PHA consisted of 3
      hydroxybutyrate (3HB), 3HV, 3H2MV at 68.4, 23.7, 7.9 mmol C%. PHA production was
      inhibited when the nutrients exceeded a certain limit. Microbial analysis
      revealed that valerate-dominant feedstock caused Delftia (53%) to become the
      prevailing group over other PHA-producing bacteria. For long-term operation, 75%
      of the biomass at the end of feast phase was collected for PHA recovery, and the
      entire process exhibited a potential to produce 5 g PHA from 1 kg sludge. These
      findings indicate that the complex valerate-dominant sludge hydrolysate can be
      used to stably produce PHA containing high 3HV and 3H2MV.

PMID- 28761107
TI  - Regulatory T-cells from pancreatic lymphnodes of patients with type-1 diabetes
      express increased levels of microRNA miR-125a-5p that limits CCR2 expression.
AB  - Autoimmune type 1 diabetes (T1D) is thought to be caused by a defective immune
      regulation with regulatory T (Treg) cells playing a fundamental role in this
      process. Tolerance mechanisms depend on tunable responses that are sensitive to
      minor perturbations in the expression of molecules that can be carried out by
      multiple epigenetic mechanisms, including regulation by microRNAs. In this study,
      microRNA expression profile was investigated in Treg cells isolated from
      peripheral blood (PB) and from pancreatic draining lymph nodes (PLN) of T1D
      patients and non-diabetic subjects. Among 72 microRNAs analyzed, miR-125a-5p
      resulted specifically hyper-expressed in Treg cells purified from PLN of T1D
      patients. TNFR2 and CCR2 were identified as miR-125a-5p target genes. Elevated
      miR-125a-5p was detected in Treg cells isolated from PLN but not from PB of
      donors with T1D and was associated with reduced CCR2 expression. A specific beta
      cell expression of the CCR2-ligand (CCL2) was observed in the pancreata of
      cadaveric donors, suggesting that beta-cells are prone to attract CCR2+ Treg
      cells. These novel data propose a mechanism, occurring in PLNs of T1D patients,
      involving increased expression of miR-125a-5p on Treg cells which results into
      reduced expression of CCR2, thus limiting their migration and eventual function
      in the pancreas.

PMID- 28761108
TI  - The advantages of endophyte-infected over uninfected tall fescue in the growth
      and pathogen resistance are counteracted by elevated CO2.
AB  - Atmospheric CO2 concentrations are predicted to double within the next century.
      Despite this trend, the extent and mechanisms through which elevated CO2 affects
      grass-endophyte symbionts remain uncertain. In the present study, the growth,
      chemical composition and pathogen resistance of endophyte-infected (E+) and
      uninfected (E-) tall fescue were compared under elevated CO2 conditions. The
      results showed that the effect of endophyte infection on the growth of tall
      fescue was significantly affected by elevated CO2. Significant advantage of E+
      over E- tall fescue in tiller number, maximum net photosynthetic rate and shoot
      biomass occurred only under ambient CO2. With CO2 concentration elevated, the
      beneficial effect of endophyte infection on the growth disappeared. Similarly,
      endophyte infection reduced lesion number and spore concentration of Curvularia
      lunata only under ambient CO2. These results suggest that the beneficial effect
      of endophyte infection on the growth and pathogen resistance of tall fescue could
      be counteracted by elevated CO2. An explanation for the counteraction may be
      found in a change in photosynthesis and nutritive quality of leaf tissue.

PMID- 28761109
TI  - Novel electrochemical route to cleaner fuel dimethyl ether.
AB  - Methanol, the simplest alcohol, and dimethyl ether, the simplest ether, are
      central compounds in the search for alternative "green" combustion fuels. In
      fact, they are generally considered as the cornerstones of the envisaged
      "Methanol Economy" scenario, as they are able to efficiently produce energy in an
      environmentally friendly manner. However, despite a massive amount of research in
      this field, the synthesis of dimethyl ether from liquid methanol has never so far
      been reported. Here we present a computational study, based on ab initio
      Molecular Dynamics, which suggests a novel synthesis route to methanol
      dehydration - leading thus to the dimethyl ether synthesis - through the
      application of strong electric fields. Besides proving the impressive catalytic
      effects afforded by the field, our calculations indicate that the obtained
      dimethyl ether is stable and that it can be progressively accumulated thanks to
      the peculiar chemical pathways characterising the methanol reaction network under
      electric field. These results suggest that the experimental synthesis of dimethyl
      ether from liquid methanol could be achieved, possibly in the proximity of field
      emitter tips.

PMID- 28761110
TI  - Characterisation and pharmacological analysis of a crustacean G protein-coupled
      receptor: the red pigment-concentrating hormone receptor of Daphnia pulex.
AB  - This is the first pharmacological characterisation of a neuropeptide G protein
      coupled receptor (GPCR) in a crustacean. We cloned the ORF of the red pigment
      concentrating hormone from a German strain of Daphnia pulex (Dappu-RPCH), as well
      as that of the cognate receptor (Dappu-RPCHR). Dappu-RPCHR has the hallmarks of
      the rhodopsin superfamily of GPCRs, and is more similar to insect adipokinetic
      hormone (AKH) receptor sequences than to receptor sequences for AKH/corazonin
      like peptide or corazonin. We provide experimental evidence that Dappu-RPCH
      specifically activates the receptor (EC50 value of 65 pM) in a mammalian cell
      based bioluminescence assay. We further characterised the properties of the
      ligands for the Dappu-RPCHR by investigating the activities of a variety of
      naturally-occurring peptides (insect AKH and crustacean RPCH peptides). The
      insect AKHs had lower EC50 values than the crustacean RPCHs. In addition, we
      tested a series of Dappu-RPCH analogues, where one residue at a time is
      systematically replaced by an alanine to learn about the relative importance of
      the termini and side chains for activation. Mainly amino acids in positions 1 to
      4 and 8 of Dappu-RPCH appear responsible for effective activation of Dappu-RPCHR.
      The substitution of Phe4 in Dappu-RPCH had the most damaging effect on its
      agonistic activity.

PMID- 28761111
TI  - Use of [C4mim]Cl for efficient extraction of caffeoylquinic acids from sweet
      potato leaves.
AB  - Sweet potato, Ipomoea batatas, is a widely cultivated vegetable worldwide. The
      leaves contain polyphenolic natural products called caffeoylquinic acids (CQAs),
      which possess biological activities including inhibition of aggregation of
      amyloid peptides. The present study describes an efficient extraction and
      isolation procedure for CQAs from sweet potato leaves using a cellulose
      dissolving ionic liquid. The results showed that, compared to methanol, use of 1
      butyl-3-methylimidazolium chloride ([C4mim]Cl) allowed the extraction of a 6.5
      fold greater amount of CQAs. This protocol will enable the efficient extraction
      of other organic compounds and biopolymers from natural materials.

PMID- 28761113
TI  - Cell fusing agent virus and dengue virus mutually interact in Aedes aegypti cell
      lines.
AB  - The genus Flavivirus contains more than 70 single-stranded, positive-sense
      arthropod-borne RNA viruses. Some flaviviruses are particularly medically
      important to humans and other vertebrates including dengue virus (DENV), West
      Nile virus, and yellow fever virus. These viruses are transmitted to vertebrates
      by mosquitoes and other arthropod species. Mosquitoes are also infected by insect
      specific flaviviruses (ISFs) that do not appear to be infective to vertebrates.
      Cell fusing agent virus (CFAV) was the first described ISF, which was discovered
      in an Aedes aegypti cell culture. We found that while CFAV infection could be
      significantly reduced by application of RNAi against the NS5 gene, removal of the
      treatment led to quick restoration of CFAV replication. Interestingly, we found
      that CFAV infection significantly enhanced replication of DENV, and vice versa,
      DENV infection significantly enhanced replication of CFAV in mosquito cells. We
      have shown that CFAV infection leads to increase in the expression of
      ribonuclease kappa (RNASEK), which is known to promote infection of viruses that
      rely on endocytosis and pH-dependent entry. Knockdown of RNASEK by dsRNA resulted
      in reduced DENV replication. Thus, increased expression of RNASEK induced by CFAV
      is likely to contribute to enhanced DENV replication in CFAV-infected cells.

PMID- 28761112
TI  - Comparative conventional and phenomics approaches to assess symbiotic
      effectiveness of Bradyrhizobia strains in soybean (Glycine max L. Merrill) to
      drought.
AB  - Symbiotic effectiveness of rhizobitoxine (Rtx)-producing strains of
      Bradyrhizobium spp. in soybean (cultivar NRC-37/Ahilya-4) under limited soil
      moisture conditions was evaluated using phenomics tools such as infrared(IR)
      thermal and visible imaging. Red, green and blue (RGB) colour pixels were
      standardized to analyse a total of 1017 IR thermal and 692 visible images. Plants
      inoculated with the Rtx-producing strains B. elkanii USDA-61 and USDA-94 and
      successive inoculation by B. diazoefficiens USDA-110 resulted in cooler canopy
      temperatures and increased canopy greenness. The results of the image analysis of
      plants inoculated with Rtx-producing strains were correlated with effective
      nodulation, improved photosynthesis, plant nitrogen status and yield parameters.
      Principal component analysis (PCA) revealed the reliability of the phenomics
      approach over conventional destructive approaches in assessing the symbiotic
      effectiveness of Bradyrhizobium strains in soybean plants under watered (87.41
      89.96%) and water-stressed (90.54-94.21%) conditions. Multivariate cluster
      analysis (MCA) revealed two distinct clusters denoting effective (Rtx) and
      ineffective (non-Rtx) Bradyrhizobium inoculation treatments in soybean.
      Furthermore, correlation analysis showed that this phenotyping approach is a
      dependable alternative for screening drought tolerant genotypes or drought
      resilience symbiosis. This is the first report on the application of non-invasive
      phenomics techniques, particularly RGB-based image analysis, in assessing plant
      microbe symbiotic interactions to impart abiotic stress tolerance.

PMID- 28761114
TI  - Absence of deformed wing virus and Varroa destructor in Australia provides unique
      perspectives on honeybee viral landscapes and colony losses.
AB  - Honeybee (Apis mellifera) health is threatened globally by the complex
      interaction of multiple stressors, including the parasitic mite Varroa destructor
      and a number of pathogenic viruses. Australia provides a unique opportunity to
      study this pathogenic viral landscape in the absence of V. destructor. We
      analysed 1,240A. mellifera colonies across Australia by reverse transcription
      polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS). Five
      viruses were prevalent: black queen cell virus (BQCV), sacbrood virus (SBV),
      Israeli acute paralysis virus (IAPV) and the Lake Sinai viruses (LSV1 and LSV2),
      of which the latter three were detected for the first time in Australia. We also
      showed several viruses were absent in our sampling, including deformed wing virus
      (DWV) and slow bee paralysis virus (SBPV). Our findings highlight that viruses
      can be highly prevalent in A. mellifera populations independently of V.
      destructor. Placing these results in an international context, our results
      support the hypothesis that the co-pathogenic interaction of V. destructor and
      DWV is a key driver of increased colony losses, but additional stressors such as
      pesticides, poor nutrition, etc. may enable more severe and frequent colony
      losses to occur.

PMID- 28761115
TI  - Hypothermia Prevents Retinal Damage Generated by Optic Nerve Trauma in the Rat.
AB  - Ocular and periocular traumatisms may result in loss of vision. Hypothermia
      provides a beneficial intervention for brain and heart conditions and, here, we
      study whether hypothermia can prevent retinal damage caused by traumatic
      neuropathy. Intraorbital optic nerve crush (IONC) or sham manipulation was
      applied to male rats. Some animals were subjected to hypothermia (8  degrees C)
      for 3 h following surgery. Thirty days later, animals were subjected to
      electroretinography and behavioral tests. IONC treatment resulted in amplitude
      reduction of the b-wave and oscillatory potentials of the electroretinogram,
      whereas the hypothermic treatment significantly (p < 0.05) reversed this process.
      Using a descending method of limits in a two-choice visual task apparatus, we
      demonstrated that hypothermia significantly (p < 0.001) preserved visual acuity.
      Furthermore, IONC-treated rats had a lower (p < 0.0001) number of retinal
      ganglion cells and a higher (p < 0.0001) number of TUNEL-positive cells than sham
      operated controls. These numbers were significantly (p < 0.0001) corrected by
      hypothermic treatment. There was a significant (p < 0.001) increase of RNA
      binding motif protein 3 (RBM3) and of BCL2 (p < 0.01) mRNA expression in the eyes
      exposed to hypothermia. In conclusion, hypothermia constitutes an efficacious
      treatment for traumatic vision-impairing conditions, and the cold-shock protein
      pathway may be involved in mediating the beneficial effects shown in the retina.

PMID- 28761116
TI  - Durability and Self-healing Effects of Hydrogel Coatings with respect to Contact
      Condition.
AB  - The self-healing property of a hydrogel applied to a glass substrate as a thin
      polymer coating was assessed. The motivation was to develop a durable hydrogel
      coating that may be used to protect the surface of precision components from
      surface damage and scratches. The intrinsic swelling behavior of hydrogel fibers
      when they are exposed to moisture was exploited to attain the self-healing
      effect. The mechanical and self-healing properties of the dehydrated hydrogel
      coating by the freeze-drying process and the hydrated hydrogel coating that was
      reconstituted by the addition of water were analyzed. After conducting sliding
      tests with different loads and sliding distances, the wear area was hydrated with
      water to successfully induce self-healing of the hydrogel coating. It was also
      found that both the dehydrated hydrogel coating and the hydrated hydrogel coating
      had improved friction characteristics. In particular, the hydrated hydrogel
      coating had a much higher durability than the dehydrated coating.

PMID- 28761117
TI  - Electron ptychographic microscopy for three-dimensional imaging.
AB  - Knowing the three-dimensional structural information of materials at the
      nanometer scale is essential to understanding complex material properties.
      Electron tomography retrieves three-dimensional structural information using a
      tilt series of two-dimensional images. In this paper, we report an alternative
      combination of electron ptychography with the inverse multislice method. We
      demonstrate depth sectioning of a nanostructured material into slices with 0.34
      nm lateral resolution and with a corresponding depth resolution of about 24-30
      nm. This three-dimensional imaging method has potential applications for the
      three-dimensional structure determination of a range of objects, ranging from
      inorganic nanostructures to biological macromolecules.Three-dimensional
      ptychographic imaging with electrons has remained a challenge because, unlike X
      rays, electrons are easily scattered by atoms. Here, Gao et al. extend multi
      slice methods to electrons in the multiple scattering regime, paving the way to
      nanometer-scale 3D structure determination with electrons.

PMID- 28761118
TI  - Bortezomib before and after high-dose therapy in myeloma: long-term results from
      the phase III HOVON-65/GMMG-HD4 trial.
AB  - The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German
      speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial
      compared bortezomib (BTZ) before and after high-dose melphalan and autologous
      stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents
      prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged
      18-65 years. Here, the long-term follow-up and data on second primary
      malignancies (SPM) are presented. After a median follow-up of 96 months,
      progression-free survival (censored at allogeneic transplantation, PFS) remained
      significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95%
      confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was
      similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The
      incidence of SPM were similar between the two arms (7% each, P=0.73). The
      negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone
      size ?10%) and renal impairment at baseline (serum creatinine >2 mg dl-1) on PFS
      and OS remained abrogated in the PAD but not VAD arm. OS from first
      relapse/progression was similar between the study arms (HR=1.02, P=0.85). In
      conclusion, the survival benefit with BTZ induction/maintenance compared with
      classical cytotoxic agents and thalidomide maintenance is maintained without an
      increased risk of SPM.

PMID- 28761119
TI  - GFusion: an Effective Algorithm to Identify Fusion Genes from Cancer RNA-Seq
      Data.
AB  - Fusion gene derived from genomic rearrangement plays a key role in cancer
      initiation. The discovery of novel gene fusions may be of significant importance
      in cancer diagnosis and treatment. Meanwhile, next generation sequencing
      technology provide a sensitive and efficient way to identify gene fusions in
      genomic levels. However, there are still many challenges and limitations
      remaining in the existing methods which only rely on unmapped reads or discordant
      alignment fragments. In this work we have developed GFusion, a novel method using
      RNA-Seq data, to identify the fusion genes. This pipeline performs multiple
      alignments and strict filtering algorithm to improve sensitivity and reduce the
      false positive rate. GFusion successfully detected 34 from 43 previously reported
      fusions in four cancer datasets. We also demonstrated the effectiveness of
      GFusion using 24 million 76 bp paired-end reads simulation data which contains 42
      artificial fusion genes, among which GFusion successfully discovered 37 fusion
      genes. Compared with existing methods, GFusion presented higher sensitivity and
      lower false positive rate. The GFusion pipeline can be accessed freely for non
      commercial purposes at: https://github.com/xiaofengsong/GFusion .

PMID- 28761120
TI  - Wetland salinity induces sex-dependent carry-over effects on the individual
      performance of a long-distance migrant.
AB  - Salinization is having a major impact on wetlands and its biota worldwide.
      Specifically, many migratory animals that rely on wetlands are increasingly
      exposed to elevated salinity on their nonbreeding grounds. Experimental evidence
      suggests that physiological challenges associated with increasing salinity may
      disrupt self-maintenance processes in these species. Nonetheless, the potential
      role of salinity as a driver of ecological carry-over effects remains unstudied.
      Here, we investigated the extent to which the use of saline wetlands during
      winter - inferred from feather stable isotope values - induces residual effects
      that carry over and influence physiological traits relevant to fitness in black
      tailed godwits Limosa limosa limosa on their northward migration. Overwintering
      males and females were segregated by wetland salinity in West Africa, with
      females mostly occupying freshwater wetlands. The use of these wetlands along a
      gradient of salinities was associated with differences in immune responsiveness
      to phytohaemagglutinin and sized-corrected body mass in godwits staging in
      southern Europe during northward migration - 3,000 km from the nonbreeding
      grounds - but in males only. These findings provide a window onto the processes
      by which wetland salinity can induce carry-over effects and can help predict how
      migratory species should respond to future climate-induced increases in salinity.

PMID- 28761121
TI  - A Glucose Sensing System Based on Transmission Measurements at Millimetre Waves
      using Micro strip Patch Antennas.
AB  - We present a sensing system operating at millimetre (mm) waves in transmission
      mode that can measure glucose level changes based on the complex permittivity
      changes across the signal path. The permittivity of a sample can change
      significantly as the concentration of one of its substances varies: for example,
      blood permittivity depends on the blood glucose levels. The proposed sensing
      system uses two facing microstrip patch antennas operating at 60 GHz, which are
      placed across interrogated samples. The measured transmission coefficient depends
      on the permittivity change along the signal path, which can be correlated to the
      change in concentration of a substance. Along with theoretical estimations, we
      experimentally demonstrate the sensing performance of the system using controlled
      laboratory samples, such as water-based glucose-loaded liquid samples. We also
      present results of successful glucose spike detection in humans during an in-vivo
      Intravenous Glucose Tolerance Test (IVGTT). The system could eventually be
      developed into a non-invasive glucose monitor for continuous monitoring of
      glucose levels for people living with diabetes, as it can detect as small as 1.33
      mmol/l (0.025 wt%) glucose concentrations in the controlled water-based samples
      satisfactorily, which is well below the typical human glucose levels of 4 mmol/l.

PMID- 28761122
TI  - Load-separation curves for the contact of self-affine rough surfaces.
AB  - There are two main approximate theories in the contact of rough solids: Greenwood
      Williamson asperity theories (GW) and Persson theories. Neither of them has been
      fully assessed so far with respect to load-separation curves. Focusing on the
      most important case of low fractal dimension (D f  = 2.2) with extensive
      numerical studies we find that: (i) Persson's theory describes well the regime of
      intermediate pressures/contact area, but requires significant corrective factors:
      the latter depend also on upper wavevector cutoff of the roughness; hence, (ii)
      Persson's theory does not predict the correct functional dependence on
      magnification; (iii) asperity theories in the discrete version even neglecting
      interaction effects are more appropriate in the range of relatively large
      separations, also to take into consideration of the large scatter in actual
      realization of the surface.

PMID- 28761123
TI  - First-order spatial coherence measurements in a thermalized two-dimensional
      photonic quantum gas.
AB  - Phase transitions between different states of matter can profoundly modify the
      order in physical systems, with the emergence of ferromagnetic or topological
      order constituting important examples. Correlations allow the quantification of
      the degree of order and the classification of different phases. Here we report
      measurements of first-order spatial correlations in a harmonically trapped two
      dimensional photon gas below, at and above the critical particle number for Bose
      Einstein condensation, using interferometric measurements of the emission of a
      dye-filled optical microcavity. For the uncondensed gas, the transverse coherence
      decays on a length scale determined by the thermal de Broglie wavelength of the
      photons, which shows the expected scaling with temperature. At the onset of Bose
      Einstein condensation, true long-range order emerges, and we observe quantum
      statistical effects as the thermal wave packets overlap. The excellent agreement
      with equilibrium Bose gas theory prompts microcavity photons as promising
      candidates for studies of critical scaling and universality in optical quantum
      gases.Phase transitions in quantum matter are related to correlation effects and
      they can change the ordering of material. Here the authors measure the first
      order spatial correlation and the de Broglie wavelength for both thermal and
      condensed form of a photonic Bose gas in a dye-filled optical microcavity.

PMID- 28761124
TI  - Phaeocystis globosa Virus DNA Polymerase X: a "Swiss Army knife", Multifunctional
      DNA polymerase-lyase-ligase for Base Excision Repair.
AB  - Phaeocystis globosa virus 16T is a giant virus that belongs to the so-called
      nucleo-cytoplasmic large DNA virus (NCLDV) group. Its linear dsDNA genome
      contains an almost full complement of genes required to participate in viral base
      excision repair (BER). Among them is a gene coding for a bimodular protein
      consisting of an N-terminal Polbeta-like core fused to a C-terminal domain
      (PgVPolX), which shows homology with NAD+-dependent DNA ligases. Analysis of the
      biochemical features of the purified enzyme revealed that PgVPolX is a
      multifunctional protein that could act as a "Swiss army knife" enzyme during BER
      since it is endowed with: 1) a template-directed DNA polymerization activity,
      preferentially acting on DNA structures containing gaps; 2) 5'-deoxyribose-5
      phosphate (dRP) and abasic (AP) site lyase activities; and 3) an NAD+-dependent
      DNA ligase activity. We show how the three activities act in concert to
      efficiently repair BER intermediates, leading us to suggest that PgVPolX may
      constitute, together with the viral AP-endonuclease, a BER pathway. This is the
      first time that this type of protein fusion has been demonstrated to be
      functional.

PMID- 28761125
TI  - Modeling Dominant and Recessive Forms of Retinitis Pigmentosa by Editing Three
      Rhodopsin-Encoding Genes in Xenopus Laevis Using Crispr/Cas9.
AB  - The utility of Xenopus laevis, a common research subject for developmental
      biology, retinal physiology, cell biology, and other investigations, has been
      limited by lack of a robust gene knockout or knock-down technology. Here we
      describe manipulation of the X. laevis genome using CRISPR/Cas9 to model the
      human disorder retinitis pigmentosa, and to introduce point mutations or
      exogenous DNA sequences. We introduced and characterized in-frame and out-of
      frame insertions and deletions in three genes encoding rhodopsin by co-injection
      of Cas9 mRNA, eGFP mRNA, and single guide RNAs into fertilized eggs. Deletions
      were characterized by direct sequencing and cloning; phenotypes were assessed by
      assays of rod opsin in retinal extracts, and confocal microscopy of cryosectioned
      and immunolabeled contralateral eyes. We obtained germline transmission of
      editing to F1 offspring. In-frame deletions frequently caused dominant retinal
      degeneration associated with rhodopsin biosynthesis defects, while frameshift
      phenotypes were consistent with knockout. We inserted eGFP or point mutations
      into rhodopsin genes by co-injection of repair fragments with homology to the
      Cas9 target sites. Our techniques can produce high frequency gene editing in X.
      laevis, permitting analysis in the F0 generation, and advancing the utility of X.
      laevis as a subject for biological research and disease modeling.

PMID- 28761127
TI  - Organocatalyzed synthesis of fluorinated poly(aryl thioethers).
AB  - The preparation of high-performance fluorinated poly(aryl thioethers) has
      received little attention compared to the corresponding poly(aryl ethers),
      despite the excellent physical properties displayed by many polysulfides. Herein,
      we report a highly efficient route to fluorinated poly(aryl thioethers) via an
      organocatalyzed nucleophilic aromatic substitution of silyl-protected dithiols.
      This approach requires low catalyst loadings, proceeds rapidly at room
      temperature, and is effective for many different perfluorinated or highly
      activated aryl monomers. Computational investigations of the reaction mechanism
      reveal an unexpected, concerted SNAr mechanism, with the organocatalyst playing a
      critical, dual-activation role in facilitating the process. Not only does this
      remarkable reactivity enable rapid access to fluorinated poly(aryl thioethers),
      but also opens new avenues for the processing, fabrication, and functionalization
      of fluorinated materials with easy removal of the volatile catalyst and TMSF
      byproducts.Fluorinated poly(aryl thioethers), unlike their poly(aryl ethers)
      counterparts, have received little attention despite excellent physical
      properties displayed by many polysulfides. Here the authors show a highly
      efficient route to fluorinated poly(aryl thioethers) via an organocatalyzed
      nucleophilic aromatic substitution of silyl-protected dithiols.

PMID- 28761126
TI  - High-T c superconductivity in undoped ThFeAsN.
AB  - Unlike the widely studied ReFeAsO series, the newly discovered iron-based
      superconductor ThFeAsN exhibits a remarkably high critical temperature of 30 K,
      without chemical doping or external pressure. Here we investigate in detail its
      magnetic and superconducting properties via muon-spin rotation/relaxation and
      nuclear magnetic resonance techniques and show that ThFeAsN exhibits strong
      magnetic fluctuations, suppressed below ~35 K, but no magnetic order. This
      contrasts strongly with the ReFeAsO series, where stoichiometric parent materials
      order antiferromagnetically and superconductivity appears only upon doping. The
      ThFeAsN case indicates that Fermi-surface modifications due to structural
      distortions and correlation effects are as important as doping in inducing
      superconductivity. The direct competition between antiferromagnetism and
      superconductivity, which in ThFeAsN (as in LiFeAs) occurs at already zero doping,
      may indicate a significant deviation of the s-wave superconducting gap in this
      compound from the standard s +/- scenario.Exploring the interplay between the
      superconducting gap and the antiferromagnetic phase in Fe-based superconductors
      remains an open issue. Here, the authors show that Fermi-surface modifications by
      means of structural distortions and correlation effects are as important as
      doping in inducing superconductivity in undoped ThFeAsN.

PMID- 28761128
TI  - Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in
      vitro and in vivo by targeting endocytic pathways.
AB  - Dengue virus (DENV) infection in neuronal cells was speculated to trigger
      neuropathy. Herein, we determined the blockade of DENV infection by targeting
      endocytic pathways in vitro and in vivo. In DENV-infected mouse brains, we
      previously showed that viral proteins are expressed in neuronal cells around the
      hippocampus with accompanying neurotoxicity. DENV caused infection, including
      entry, double-stranded (ds)RNA replication, protein expression, and virus
      release, followed by cytotoxicity in the mouse neuronal Neuro-2a cell line.
      Pharmacologically blocking clathrin-mediated endocytosis of the DENV retarded
      viral replication. Targeting vacuolar-type H+-ATPase (V-ATPase)-based endosomal
      acidification effectively blocked the DENV replication process, but had no direct
      effect on viral translation. Blockade of the clathrin- and V-ATPase-based
      endocytic pathways also attenuated DENV-induced neurotoxicity. Inhibiting
      endosomal acidification effectively retarded DENV infection, acute viral
      encephalitis, and mortality. These results demonstrate that clathrin mediated
      endocytosis of DENV followed by endosomal acidification-dependent viral
      replication in neuronal cells, which can lead to neurotoxicity.

PMID- 28761129
TI  - Constructal law analysis of Cl- transport in eyes aqueous humor.
AB  - Progressive loss-of-vision related to any intraocular disorder is known as
      glaucoma. Secretion of aqueous humor is physiologically important to provide
      nutrients and oxygen to the avascular anterior segment and ensuring normal visual
      function, even if, nowadays reducing the secretory rate to lower intraocular
      pressure is a major strategy in treating glaucomatous patients. Understanding the
      mechanisms and regulation of aqueous humor formation is very important to develop
      possible new approaches to lower intraocular pressure,but today there isn't any
      comprehensive model of the regulation of these component in forming aqueous
      humor. In this paper Construcal law is used to suggest how the Cl- fluxes can
      determine the water inflow and outflow, and, consequently, how the intraocular
      pressure is controlled by these fluxes.

PMID- 28761131
TI  - Dirac Magnon Nodal Loops in Quasi-2D Quantum Magnets.
AB  - In this report, we propose a new concept of one-dimensional (1D) closed lines of
      Dirac magnon nodes in two-dimensional (2D) momentum space of quasi-2D quantum
      magnetic systems. They are termed "2D Dirac magnon nodal-line loops". We utilize
      the bilayer honeycomb ferromagnets with intralayer coupling J and interlayer
      coupling J L , which is realizable in the honeycomb chromium compounds CrX3 (X =
      Br, Cl, and I). However, our results can also exist in other layered quasi-2D
      quantum magnetic systems. Here, we show that the magnon bands of the bilayer
      honeycomb ferromagnets overlap for J L  ? 0 and form 1D closed lines of Dirac
      magnon nodes in 2D momentum space. The 2D Dirac magnon nodal-line loops are
      topologically protected by inversion and time-reversal symmetry. Furthermore, we
      show that they are robust against weak Dzyaloshinskii-Moriya interaction Delta DM
      < J L and possess chiral magnon edge modes.

PMID- 28761130
TI  - Lipodystrophy and obesity are associated with decreased number of T cells with
      regulatory function and pro-inflammatory macrophage phenotype.
AB  - BACKGROUND/OBJECTIVES: In lipodystrophy (LD) adipose tissue function to store
      lipids is impaired, leading to metabolic syndrome, similar to that found in
      obesity. Emerging evidence links dysmetabolism with disorders of the immune
      system. Our aim is to investigate whether T-cell populations with regulatory
      function and monocyte-derived macrophages (MDMs) are affected by LD and obesity.
      SUBJECTS/METHODS: Blood was collected from 16 LD, 16 obese (OB, BMI>30 kg m-2)
      and 16 healthy normal-weight women (CNT). Physical parameters, plasma lipid
      profile, glucose, HbA1c, leptin levels were determined. Flow cytometry was
      employed to assess the number of circulating CD4+/CD25hi regulatory T cells
      (Tregs) and invariant natural killer T (iNKT) cells. Characterization of MDMs
      included: 1. morphological/oil-Red-O staining analyses to define two morphotypes:
      lipid laden (LL) and spindle-like (sp) MDM; 2. gene expression studies; 3. use of
      conditioned medium from MDMs (MDMs CM) on human SGBS cells. RESULTS: As compared
      to CNT, LD and, to a lesser extent, obesity were associated with reduced Tregs
      and iNKTs (P<0.001 and P<0.01 for LD and OB, respectively), higher number of LL
      MDMs (P<0.001 and P<0.01 for LD and OB, respectively), lower number of sp-MDMs
      (P<0.001 for both LD and OB), which correlated with increased paracrine
      stimulation of lipid accumulation in cells (P<0.001 and P<0.01 for LD and OB,
      respectively). LD MDMs showed decreased and increased expression for anti
      inflammatory (IL10 and CD163) and pro-inflammatory (CD68 and CCL20) marker genes,
      respectively. Analysis of correlation indicated that Tregs are directly related
      with HDL (P<0.01) and inversely related with LL-MDM (P<0.001) and that LL-MDM are
      directly related with triglycerides (P<0.01) and oxidized LDL (P<0.01).
      CONCLUSIONS: LD and obesity are associated with changes in the immune system: a
      significant reduction in the number of T cells with regulatory function and a
      shift of MDM towards lipid accumulation. Lipid profile of the patients correlates
      with these changes.

PMID- 28761132
TI  - Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the
      hypothalamus.
AB  - Exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been
      shown to reduce food intake and to increase proopiomelanocortin (POMC) gene
      expression in the hypothalamus. In this study, we examined the potential neural
      mechanisms by which these effects occur. Male Sprague Dawley rats were implanted
      with a cannula in the third ventricle of the brain through which an inhibitor of
      phosphatidylinositol-3 kinase (PI3K) (wortmannin) was administered, and EX-4 or
      vehicle was administered via intraperitoneal (IP) injection. The activity of
      PI3K/protein kinase B (AKT) and insulin receptor substrate-1 (IRS-1) in the
      hypothalamic arcuate was determined. We found that EX-4 treatment significantly
      decreased food intake and body weight. However, there were almost no changes in
      food intake and body weight when wortmannin injection (into the third ventricle)
      occurred prior to EX-4 IP injection. EX-4 not only increased the activity of
      PI3K/AKT, but it also increased IRS-1 activity. These results show that EX-4
      likely suppresses food intake due to its ability to enhance insulin signaling.

PMID- 28761133
TI  - Protected State Transfer via an Approximate Quantum Adder.
AB  - We propose a decoherence protected protocol for sending single photon quantum
      states through depolarizing channels. This protocol is implemented via an
      approximate quantum adder engineered through spontaneous parametric down
      converters, and shows higher success probability than distilled quantum
      teleportation protocols for distances below a threshold depending on the
      properties of the channel.

PMID- 28761136
TI  - Effects of elevated CO2 on phytoplankton during a mesocosm experiment in the
      southern eutrophicated coastal water of China.
AB  - There is a growing consensus that the ongoing increase in atmospheric CO2 level
      will lead to a variety of effects on marine phytoplankton and ecosystems.
      However, the effects of CO2 enrichment on eutrophic coastal waters are still
      unclear, as are the complex mechanisms coupled to the development of
      eutrophication. Here, we report the first mesocosm CO2 perturbation study in a
      eutrophic subtropical bay during summer by investigating the effect of rising CO2
      on a model artificial community consisting of well-characterized cultured diatoms
      (Phaeodactylum tricornutum and Thalassiosira weissflogii) and prymnesiophytes
      (Emiliania huxleyi and Gephyrocapsa oceanica). These species were inoculated into
      triplicate 4 m3 enclosures with equivalent chlorophyll a (Chl-a) under present
      and higher partial pressures of atmospheric CO2 (pCO2 = 400 and 1000 ppmv).
      Diatom bloom events were observed in all enclosures, with enhanced organic carbon
      production and Chl-a concentrations under high CO2 treatments. Relative to the
      low CO2 treatments, the consumption of the dissolved inorganic nitrogen and
      uptake ratios of N/P and N/Si increased significantly during the bloom. These
      observed responses suggest more extensive and complex effects of higher CO2
      concentrations on phytoplankton communities in coastal eutrophic environments.

PMID- 28761134
TI  - The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by
      suppressing oxidative stress and excessive calpain activation.
AB  - We found that hesperidin, a plant-derived bioflavonoid, may be a candidate agent
      for neuroprotective treatment in the retina, after screening 41 materials for
      anti-oxidative properties in a primary retinal cell culture under oxidative
      stress. We found that the intravitreal injection of hesperidin in mice prevented
      reductions in markers of the retinal ganglion cells (RGCs) and RGC death after N
      methyl-D-aspartate (NMDA)-induced excitotoxicity. Hesperidin treatment also
      reduced calpain activation, reactive oxygen species generation and TNF-alpha gene
      expression. Finally, hesperidin treatment improved electrophysiological function,
      measured with visual evoked potential, and visual function, measured with
      optomotry. Thus, we found that hesperidin suppressed a number of cytotoxic
      factors associated with NMDA-induced cell death signaling, such as oxidative
      stress, over-activation of calpain, and inflammation, thereby protecting the RGCs
      in mice. Therefore, hesperidin may have potential as a therapeutic supplement for
      protecting the retina against the damage associated with excitotoxic injury, such
      as occurs in glaucoma and diabetic retinopathy.

PMID- 28761137
TI  - A 4D view on the evolution of metamorphic dehydration reactions.
AB  - Metamorphic reactions influence the evolution of the Earth's crust in a range of
      tectonic settings. For example hydrous mineral dehydration in a subducting slab
      can produce fluid overpressures which may trigger seismicity. During reaction the
      mechanisms of chemical transport, including water expulsion, will dictate the
      rate of transformation and hence the evolution of physical properties such as
      fluid pressure. Despite the importance of such processes, direct observation of
      mineral changes due to chemical transport during metamorphism has been previously
      impossible both in nature and in experiment. Using time-resolved (4D) synchrotron
      X-ray microtomography we have imaged a complete metamorphic reaction and show how
      chemical transport evolves during reaction. We analyse the dehydration of gypsum
      to form bassanite and H2O which, like most dehydration reactions, produces a
      solid volume reduction leading to the formation of pore space. This porosity
      surrounds new bassanite grains producing fluid-filled moats, across which
      transport of dissolved ions to the growing grains occurs via diffusion. As moats
      grow in width, diffusion and hence reaction rate slow down. Our results
      demonstrate how, with new insights into the chemical transport mechanisms, we can
      move towards a more fundamental understanding of the hydraulic and chemical
      evolution of natural dehydrating systems.

PMID- 28761138
TI  - An atypical strictosidine synthase, OsSTRL2, plays key roles in anther
      development and pollen wall formation in rice.
AB  - Strictosidine synthase (STR) plays an important role in the biosynthesis of
      terpenoid indole alkaloids (TIAs) and is expressed in a range of active
      meristematic tissues of higher plants. STR proteins are involved in different
      physiological and biochemical pathways. However, the function of STR proteins in
      rice development remains poorly understood. In this study, we identified 21
      possible STR-like (OsSTRL) family members in rice genome and found that only one
      gene, OsSTRL2, exhibited a pre-emergency specific florescence expression pattern.
      Tissue-specific expression profile analysis, beta-glucuronidase histochemical
      (GUS) staining and RNA in situ hybridization confirmed that OsSTRL2 was highly
      expressed in tapetal cells and microspores. Comparative protein sequence analysis
      indicated that OsSTRL2 lacked the key catalytic residue found in a typical STR
      (STR1), although it possessed conserved beta-propellers and alpha-helices formed
      the basic structure of STR1. OsSTRL2 knockout mutant resulted to male sterility
      because of the defects in anther development and pollen wall formation.
      Subcellular localization of OsSTRL2-YFP revealed that the OsSTRL2 protein was
      primarily localized in the endoplasmic reticulum (ER). Therefore, OsSTRL2 is an
      atypical strictosidine synthase that plays crucial roles in regulating anther
      development and pollen wall formation in rice.

PMID- 28761139
TI  - Biosynthesis of brain cytoplasmic 200 RNA.
AB  - Brain cytoplasmic 200 RNA (BC200 RNA), a neuron-specific non-coding RNA, is also
      highly expressed in a number of tumors of non-neuronal origin. However, the
      biosynthesis of BC200 RNA remains poorly understood. In this study, we show that
      the efficient transcription of BC200 RNA requires both internal and upstream
      promoter elements in cancer cells. The transcription complex seems to interact
      with a broad range of sequences within the upstream 100-bp region. The cellular
      levels and half-lives of BC200 RNA were found to differ across various cancer
      cell types, but there was no significant correlation between these parameters.
      Exogenously expressed BC200 RNA had a shorter half-life than that observed for
      the endogenous version in cancer cells, suggesting that BC200 RNA might be
      protected by some limiting factor(s) in cancer cells. Transient transfection
      experiments showed that the transcriptional activity of the exogenous BC200 RNA
      promoter element varied depending on the cancer cell type. However, the promoter
      activities together with the half-life data could not explain the differences in
      the levels of BC200 RNA among different cell types, suggesting that there is
      another level of transcriptional regulation beyond that detected by our transient
      transfection experiments.

PMID- 28761140
TI  - Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a
      humanized mouse model.
AB  - Combination anti-retroviral therapy (cART) has drastically improved the clinical
      outcome of HIV-1 infection. Nonetheless, despite effective cART, HIV-1 persists
      indefinitely in infected individuals. Clonal expansion of HIV-1-infected cells in
      peripheral blood has been reported recently. cART is effective in stopping the
      retroviral replication cycle, but not in inhibiting clonal expansion of the
      infected host cells. Thus, the proliferation of HIV-1-infected cells may play a
      role in viral persistence, but little is known about the kinetics of the
      generation, the tissue distribution or the underlying mechanism of clonal
      expansion in vivo. Here we analyzed the clonality of HIV-1-infected cells using
      high-throughput integration site analysis in a hematopoietic stem cell
      transplanted humanized mouse model. Clonally expanded, HIV-1-infected cells were
      detectable at two weeks post infection, their abundance increased with time, and
      certain clones were present in multiple organs. Expansion of HIV-1-infected
      clones was significantly more frequent when the provirus was integrated near host
      genes in specific gene ontological classes, including cell activation and
      chromatin regulation. These results identify potential drivers of clonal
      expansion of HIV-1-infected cells in vivo.

PMID- 28761141
TI  - Effects of pulpotomy using mineral trioxide aggregate on prostaglandin
      transporter and receptors in rat molars.
AB  - Mineral trioxide aggregate (MTA) is a commonly used dental pulp-capping material
      with known effects in promoting reparative dentinogenesis. However, the mechanism
      by which MTA induces dentine repair remains unclear. The aim of the present study
      was to investigate the role of prostaglandin E2 (PGE2) in dentine repair by
      examining the localisation and mRNA expression levels of its transporter (Pgt)
      and two of its receptors (Ep2 and Ep4) in a rat model of pulpotomy with MTA
      capping. Ep2 expression was detected in odontoblasts, endothelial cells, and
      nerve fibres in normal and pulpotomised tissues, whereas Pgt and Ep4 were
      immunolocalised only in the odontoblasts. Moreover, mRNA expression of Slco2a1
      (encoding Pgt), Ptger2 (encoding Ep2), and Ptger4 (encoding Ep4) was
      significantly upregulated in pulpotomised dental pulp and trigeminal ganglia
      after MTA capping. Our results provide insights into the functions of PGE2 via
      Pgt and Ep receptors in the healing dentine/pulp complex and may be helpful in
      developing new therapeutic targets for dental disease.

PMID- 28761143
TI  - All solution-processed micro-structured flexible electrodes for low-cost light
      emitting pressure sensors fabrication.
AB  - Recent studies have demonstrated the advantage of developing pressure-sensitive
      devices with light-emitting properties for direct visualization of pressure
      distribution, potential application to next generation touch panels and human
      machine interfaces. To ensure that this technology is available to everyone, its
      production cost should be kept as low as possible. Here, simple device concepts,
      namely, pressure sensitive flexible hybrid electrodes and OLED architecture, are
      used to produce low-cost resistive or light-emitting pressure sensors.
      Additionally, integrating solution-processed self-assembled micro-structures into
      the flexible hybrid electrodes composed of an elastomer and conductive materials
      results in enhanced device performances either in terms of pressure or spatial
      distribution sensitivity. For instance, based on the pressure applied, the
      measured values for the resistances of pressure sensors range from a few MOmega
      down to 500 Omega. On the other hand, unlike their evaporated equivalents, the
      combination of solution-processed flexible electrodes with an inverted OLED
      architectures display bright green emission when a pressure over 200 kPa is
      applied. At a bias of 3 V, their luminance can be tuned by applying a higher
      pressure of 500 kPa. Consequently, features such as fingernails and fingertips
      can be clearly distinguished from one another in these long-lasting low-cost
      devices.

PMID- 28761142
TI  - Methylation profile of a satellite DNA constituting the intercalary G+C-rich
      heterochromatin of the cut trough shell Spisula subtruncata (Bivalvia,
      Mactridae).
AB  - Tandemly repeated DNAs usually constitute significant portions of eukaryotic
      genomes. In bivalves, however, repetitive DNAs are habitually not widespread. In
      our search for abundant repetitive DNAs in trough shells, we discovered a novel
      satellite DNA, SSUsat, which constitutes at least 1.3% of the genome of Spisula
      subtruncata. As foreseen by the satellite DNA library hypothesis, we confirmed
      that this satellite DNA is also present in two other Mactridae species, showing a
      highly conserved nucleotide sequence together with a dramatic diminution in the
      number of repeats. Predominantly located at the G + C-rich intercalary
      heterochromatin of S. subtruncata, SSUsat displays several DNA methylation
      peculiarities. The level of methylation of SSUsat is high (3.38%) in comparison
      with bivalve standards and triplicates the mean of the S. subtruncata genome
      (1.13%). Methylation affects not only the cytosines in CpG dinucleotides but also
      those in CHH and CHG trinucleotides, a feature common in plants but scarce and
      without any clear known relevance in animals. SSUsat segments enriched in
      methylated cytosines partly overlap those showing higher sequence conservation.
      The presence of a chromosome pair showing an accumulation of markedly under
      methylated SSUsat monomers additionally indicates that the methylation processes
      that shape repetitive genome compartments are quite complex.

PMID- 28761144
TI  - Plant survival and keystone pollinator species in stochastic coextinction models:
      role of intrinsic dependence on animal-pollination.
AB  - Coextinction models are useful to understand community robustness to species loss
      and resilience to disturbances. We simulated pollinator extinctions in
      pollination networks by using a hybrid model that combined a recently developed
      stochastic coextinction model (SCM) for plant extinctions and a topological model
      (TCM) for animal extinctions. Our model accounted for variation in interaction
      strengths and included empirical estimates of plant dependence on pollinators to
      set seeds. The stochastic nature of such model allowed us determining plant
      survival to single (and multiple) extinction events, and identifying which
      pollinators (keystone species) were more likely to trigger secondary extinctions.
      Consistently across three different pollinator removal sequences, plant
      robustness was lower than in a pure TCM, and plant survival was more determined
      by dependence on the mutualism than by interaction strength. As expected, highly
      connected and dependent plants were the most sensitive to pollinator loss and
      collapsed faster in extinction cascades. We predict that the relationship between
      dependence and plant connectivity is crucial to determine network robustness to
      interaction loss. Finally, we showed that honeybees and several beetles were
      keystone species in our communities. This information is of great value to
      foresee consequences of pollinator losses facing current global change and to
      identify target species for effective conservation.

PMID- 28761145
TI  - Large-scale differences in microbial biodiversity discovery between 16S amplicon
      and shotgun sequencing.
AB  - Modern metagenomic environmental DNA studies are almost completely reliant on
      next-generation sequencing, making evaluations of these methods critical. We
      compare two next-generation sequencing techniques - amplicon and shotgun - on
      water samples across four of Brazil's major river floodplain systems (Amazon,
      Araguaia, Parana, and Pantanal). Less than 50% of phyla identified via amplicon
      sequencing were recovered from shotgun sequencing, clearly challenging the dogma
      that mid-depth shotgun recovers more diversity than amplicon-based approaches.
      Amplicon sequencing also revealed ~27% more families. Overall the amplicon data
      were more robust across both biodiversity and community ecology analyses at
      different taxonomic scales. Our work doubles the sampling size in similar
      environmental studies, and novelly integrates environmental data (e.g., pH,
      temperature, nutrients) from each site, revealing divergent correlations
      depending on which data are used. While myriad variants on NGS techniques and
      bioinformatic pipelines are available, our results point to core differences that
      have not been highlighted in any studies to date. Given the low number of taxa
      identified when coupling shotgun data with clade-based taxonomic algorithms,
      previous studies that quantified biodiversity using such bioinformatic tools
      should be viewed cautiously or re-analyzed. Nonetheless, shotgun has
      complementary advantages that should be weighed when designing projects.

PMID- 28761146
TI  - How gastrin-releasing peptide receptor (GRPR) and alphavbeta3 integrin expression
      reflect reorganization features of tumors after hyperthermia treatments.
AB  - The outcome of tumor treatment via hyperthermia in the clinic has been reported
      to be heterogeneous. Here, we assessed how the presence of gastrin-releasing
      peptide receptor (GRPR) and alphavbeta3 integrin together with the morphology of
      the vascularization reflects the growth behavior of tumors after hyperthermia
      treatment. MDA-MB-231 tumor bearing mice were treated either with high (46 
      degrees C) or low dose (42  degrees C) water hyperthermia for 60 min. Changes of
      GRPR and alphavbeta3 integrin expression were assessed via multiplexed optical
      imaging. Vascularization was reconstructed and quantified by uCT imaging after
      contrast agent injection. We found that high dose hyperthermia is capable of
      increasing the expression of GRPR, alphavbeta3 integrin, CD31, and Ki67 in
      tumors. Also the morphology of tumor vasculature changed (increased relative
      blood volume and small-diameter vessel density, decreased expression of alpha
      SMA). Low dose hyperthermia induced comparatively moderate effects on the
      investigated protein expression pattern and vascular remodeling. We conclude that
      under defined circumstances, specific temperature doses affect the reorganization
      of tumor regrowth, which is triggered by residual "dormant" cells even though
      tumor volumes are transiently decreasing. Further on, GRPR, alphavbeta3 integrin
      expression are versatile tools to surveil potential tumor regrow during therapy,
      beyond the conventional determination of tumor volumes.

PMID- 28761147
TI  - Cytologically indeterminate thyroid nodules: increased diagnostic performance
      with combination of US TI-RADS and a new scoring system.
AB  - To investigate the diagnostic performance of combination of ultrasound (US)
      thyroid imaging reporting and data system (TI-RADS) and a new US scoring system
      for diagnosing thyroid nodules (TNs) with indeterminate results (Bethesda
      categories III, IV and V) on fine-needle aspiration (FNA) cytology. 453 patients
      with 453 cytologically indeterminate TNs were included in this study.
      Multivariate analyses were performed to construct the scoring system. The
      diagnostic performances of TI-RADS and the combined method were evaluated and
      compared. Multivariate analyses revealed that marked hypoechogenicity, taller
      than wide shape and absence of halo sign were independent predictors for
      malignancy in cytologically indeterminate TNs. Scoring system was thereafter
      defined as follows: risk score (RS) = 3.2 x (if marked hypoechogenicity) + 2.8 x
      (if taller than wide shape) + 1.3 x (if absence of halo sign). Compared with TI
      RADS alone, the areas under the receiver operating characteristic curves (AUC),
      specificity, accuracy and positive predictive value (PPV) of the combined method
      increased significantly with 0.731 versus 0.569, 48.5% versus 14.1%, 76.2% versus
      62.3%, and 70.9% versus 59.9%, respectively (all P < 0.05). The combination of TI
      RADS and new US scoring system showed superior diagnostic performances in
      predicting malignant TNs with indeterminate FNA cytology results in comparison
      with TI-RADS alone.

PMID- 28761149
TI  - The relationships between serum fructosamine concentrations and lipid profiles in
      community-dwelling adults.
AB  - We examined the epidemiological associations between serum fructosamine and
      dyslipidemia indices in community-dwelling adults. Clinical characteristics and
      lipid profiles were analyzed in 1352 community-dwelling adults. The demographic
      characteristics and laboratory results were grouped according to the quartiles of
      serum fructosamine concentrations in all eligible individuals. From the bottom to
      the top quartile of serum fructosamine, there were graded increases in age, total
      cholesterol (TC), fasting blood glucose (FBG), total protein (TP), triglyceride
      (TG), total cholesterol/ high density lipoprotein-cholesterol (TC/HDL-C) and
      atherogenic index of plasma (AIP). Serum fructosamine was positive correlated
      with age, TC, FBG, TP, TG, TC/HDL-C and AIP in whole individuals. The positive
      correlations were then observed in both genders between serum fructosamine and
      TC, FBG, TP, TG. Two dominant factors were identified by principal component
      analysis. Logistic regression analysis showed that the two factors were
      associated with increased serum fructosamine with adjustment for gender, age,
      body mass index (BMI), FBG and TP. The similar results were observed in males,
      but not in females. Dyslipidemia tends to contribute to increased serum
      fructosamine concentrations in study population, suggesting that elevated serum
      fructosamine may herald an increased risk of cardiovascular disease among
      community-dwelling adults, especially in males.

PMID- 28761148
TI  - Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5.
AB  - The highly conserved Wnt signaling pathway regulates cell proliferation and
      differentiation in vertebrates and invertebrates. Upon binding of a Wnt ligand to
      a receptor of the Fz family, Disheveled (Dsh/Dvl) transduces the signal during
      canonical and non-canonical Wnt signaling. The specific details of how this
      process occurs have proven difficult to study, especially as Dsh appears to
      function as a switch between different branches of Wnt signaling. Here we focus
      on the membrane-proximal events that occur once Dsh is recruited to the membrane.
      We show that membrane-tethering of the Dsh protein is sufficient to induce
      canonical Wnt signaling activation even in the absence of the Wnt co-receptor
      Arrow/LRP5/6. We map the protein domains required for pathway activation in
      membrane tethered constructs finding that both the DEP and PDZ domains are
      dispensable for canonical signaling only in membrane-tethered Dsh, but not in
      untethered/normal Dsh. These data lead to a signal activation model, where Arrow
      is required to localize Dsh to the membrane during canonical Wnt signaling
      placing Dsh downstream of Arrow.

PMID- 28761150
TI  - Single genetic locus improvement of iron, zinc and beta-carotene content in rice
      grains.
AB  - Nearly half of the world's population obtains its daily calories from rice
      grains, which lack or have insufficient levels of essential micronutrients. The
      deficiency of micronutrients vital for normal growth is a global health problem,
      and iron, zinc and vitamin A deficiencies are the most prevalent ones. We
      developed rice lines expressing Arabidopsis NICOTIANAMINE SYNTHASE 1 (AtNAS1),
      bean FERRITIN (PvFERRITIN), bacterial CAROTENE DESATURASE (CRTI) and maize
      PHYTOENE SYNTHASE (ZmPSY) in a single genetic locus in order to increase iron,
      zinc and beta-carotene content in the rice endosperm. NAS catalyzes the synthesis
      of nicotianamine (NA), which is a precursor of deoxymugeneic acid (DMA) iron and
      zinc chelators, and also chelate iron and zinc for long distance transport.
      FERRITIN provides efficient storage of up to 4500 iron ions. PSY catalyzes the
      conversion of GGDP to phytoene, and CRTI performs the function of desaturases
      required for the synthesis of beta-carotene from phytoene. All transgenic rice
      lines have significantly increased beta-carotene, iron, and zinc content in the
      polished rice grains. Our results establish a proof-of-concept for multi-nutrient
      enrichment of rice grains from a single genetic locus, thus offering a
      sustainable and effective approach to address different micronutrient
      deficiencies at once.

PMID- 28761151
TI  - Epauletted fruit bats display exceptionally high infections with a Hepatocystis
      species complex in South Sudan.
AB  - Hepatocystis parasites are closely related to mammalian Plasmodium species, the
      causative agents of malaria. Despite the close phylogenetic relationship,
      Hepatocystis parasites lack the intermittent erythrocytic replication cycles, the
      signature and exclusive cause of malaria-related morbidity and mortality.
      Hepatocystis population expansion in the mammalian host is thought to be
      restricted to the pre-erythrocytic liver phase. Complete differentiation of first
      generation blood stages into sexual stages for subsequent vector transmission
      indicates alternative parasite/host co-evolution. In this study, we identified a
      region of exceptionally high prevalence of Hepatocystis infections in Old World
      fruit bats in South Sudan. Investigations over the course of five consecutive
      surveys revealed an average of 93 percent prevalence in four genera of African
      epauletted fruit bats. We observed a clear seasonal pattern and tolerance of high
      parasite loads in these bats. Phylogenetic analyses revealed several cryptic
      Hepatocystis parasite species and, in contrast to mammalian Plasmodium parasites,
      neither host specificity nor strong geographical patterns were evident. Together,
      our study provides evidence for Pan-African distribution and local high
      endemicity of a Hepatocystis species complex in Pteropodidae.

PMID- 28761152
TI  - Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress
      reduction and AMPKalpha-regulated autophagy induction in streptozotocin-induced
      diabetic nephropathy.
AB  - Aberrant endoplasmic reticulum (ER) stress and autophagy are associated with
      diabetic nephropathy. Here we investigated the effect of astragaloside IV (AS-IV)
      on the progression of diabetic nephropathy (DN) and the underlying mechanism
      involving ER stress and autophagy in streptozotocin (STZ)-induced diabetic mice
      and high glucose (HG)-incubated podocytes. The diabetic mice developed
      progressive albuminuria and glomerulosclerosis within 8 weeks, which were
      significantly ameliorated by AS-IV treatment in a dose-dependent manner.
      Moreover, diabetes or HG-induced podocyte apoptosis was markedly attenuated by AS
      IV, paralleled by a marked remission in ER stress and a remarkable restoration in
      impaired autophagy, which were associated with a significant improvement in the
      expression of sarcoendoplasmic reticulum Ca2+ ATPase 2b (SERCA2b) and AMP
      activated protein kinase alpha (AMPKalpha) phosphorylation, respectively.
      Knockdown of SERCA2 in podocytes induced ER stress and largely abolished the
      protective effect of AS-IV, but had no obvious effect on the expression of
      autophagy-associated proteins. On the other hand, blockade of either autophagy
      induction or AMPKalpha activation could also significantly mitigate AS-IV-induced
      beneficial effect. Collectively, these results suggest that AS-IV prevented the
      progression of DN, which is mediated at least in part by SERCA2-dependent ER
      stress attenuation and AMPKalpha-promoted autophagy induction.

PMID- 28761153
TI  - PLA2R binds to the annexin A2-S100A10 complex in human podocytes.
AB  - Phospholipase A2 receptor (PLA2R) is a member of the mannose receptor family
      found in podocytes in human kidney. PLA2R is the target of the autoimmune
      disease, membranous nephropathy, characterised by production of anti-PLA2R
      autoantibodies which bind to the podocyte. However the function of PLA2R in
      health and in disease remains unclear. To gain insight into the molecular
      mechanisms of PLA2R function, we searched for its endogenous binding partners.
      Proteomic analysis identified annexinA2 as a potential interactor with the
      extracellular domains of PLA2R. We confirmed that PLA2R binds to annexinA2
      S100A10 (A2t) complex with specific high affinity to the S100A10 component. The
      binding occured within the PLA2R NC3 fragment and was increased in acidic pH.
      Furthermore Ca2+ promoted the association of the PLA2R-A2t complex with
      phospholipid membranes in vitro. Within the podocyte, all three proteins were
      enriched in the plasma membrane and organelle membrane compartments. PLA2R co
      localised with S100A10 at the cell surface and in extracellular vesicles. This
      novel interaction between PLA2R and the A2t complex offers insights into the role
      of PLA2R in podocytes and how autoantibodies might disrupt PLA2R function. The
      ability of podocytes to secrete vesicles containing PLA2R provides a route for
      engagement of PLA2R with the immune system.

PMID- 28761154
TI  - Broadband and thin magnetic absorber with non-Foster metasurface for admittance
      matching.
AB  - One of the long-standing and challenging problems in microwave engineering is the
      realization of ultra-wideband absorption using extremely-thin structures.
      Magnetic material can facilitate thickness reduction for microwave absorbers but
      also bring inherent narrowband admittance matching conundrum originating from its
      frequency-dispersive permeability and high permittivity. In this paper, we
      propose a simple and yet effective solution based on the concept of admittance
      matching with non-Foster metasurface (NFMS). Building on this concept, an ultra
      wideband and extremely-thin magnetic absorber is achieved, with a simple
      structure consisting of a conductor-backed magnetic sheet (CMBS) coated by a
      NFMS. The NFMS with negatively inductive susceptance can properly cancel its
      positively frequency-dispersive counterpart from the CMBS so that constructive
      interference near the absorber can be obtained over a wide frequency band.
      Furthermore, the NFMS will compensate the surface conductance required for
      maximum incident power dissipation. As an example, we demonstrate an absorber
      with one-frequency decade bandwidth and a thickness of only 1/255 wavelength at
      the lowest operation frequency. The proposed concept enables versatile admittance
      matching techniques using a single-layered and has the potential to be used in
      the development of interesting low-profile and broadband microwave devices.

PMID- 28761155
TI  - Spatial structure of TLR4 transmembrane domain in bicelles provides the insight
      into the receptor activation mechanism.
AB  - Toll-like receptors (TLRs) play a key role in the innate and adaptive immune
      systems. While a lot of structural data is available for the extracellular and
      cytoplasmic domains of TLRs, and a model of the dimeric full-length TLR3 receptor
      in the active state was build, the conformation of the transmembrane (TM) domain
      and juxtamembrane regions in TLR dimers is still unclear. In the present work, we
      study the transmembrane and juxtamembrane parts of human TLR4 receptor using
      solution NMR spectroscopy in a variety of membrane mimetics, including
      phospholipid bicelles. We show that the juxtamembrane hydrophobic region of TLR4
      includes a part of long TM alpha-helix. We report the dimerization interface of
      the TM domain and claim that long TM domains with transmembrane charged
      aminoacids is a common feature of human toll-like receptors. This fact is
      analyzed from the viewpoint of protein activation mechanism, and a model of full
      length TLR4 receptor in the dimeric state has been proposed.

PMID- 28761156
TI  - Aggravation of collagen-induced arthritis by orally administered Porphyromonas
      gingivalis through modulation of the gut microbiota and gut immune system.
AB  - Porhyromonas gingivalis, a causative bacterium of periodontitis, is implicated in
      the etiology of rheumatoid arthritis (RA), mainly because of expressing peptidyl
      arginine deiminase (PAD) that generates RA-related autoantigens. However,
      compared with other periodontopathic bacteria, the precise role of P. gingivalis
      in RA is largely unknown. We found that orally administered P. gingivalis changed
      the gut microbiome with concomitant elevation of serum endotoxin and inflammatory
      markers, and impairment of the gut barrier function. Based on findings showing a
      relationship between gut microbiota and RA, we investigated whether the change of
      gut microbiota induced by P. gingivalis and Prevotella intermedia, another
      periodontopathic bacterium without PAD, is associated with collagen-induced
      arthritis (CIA). DBA/1J mice were orally administered with or without bacteria
      followed by induction of CIA. P. gingivalis, but not P. intermedia,
      administration significantly aggravated arthritis with increased interleukin-17
      levels in sera and culture supernatants, increased Th17 cell proportions among
      mesenteric lymphocytes, and a significant change in the gut microbiome. However,
      P. gingivalis administration did not elevate the level of anti-citrullinated
      protein antibody. These results suggest a unique role of P. gingivalis in the
      link between periodontitis and RA by affecting the gut immune system and the gut
      microbiota composition.

PMID- 28761157
TI  - Sorting at embryonic boundaries requires high heterotypic interfacial tension.
AB  - The establishment of sharp boundaries is essential for segregation of embryonic
      tissues during development, but the underlying mechanism of cell sorting has
      remained unclear. Opposing hypotheses have been proposed, either based on global
      tissue adhesive or contractile properties or on local signalling through cell
      contact cues. Here we use ectoderm-mesoderm separation in Xenopus to directly
      evaluate the role of these various parameters. We find that ephrin-Eph-based
      repulsion is very effective at inducing and maintaining separation, whereas
      differences in adhesion or contractility have surprisingly little impact.
      Computer simulations support and generalise our experimental results, showing
      that a high heterotypic interfacial tension between tissues is key to their
      segregation. We propose a unifying model, in which conditions of sorting
      previously considered as driven by differential adhesion/tension should be viewed
      as suboptimal cases of heterotypic interfacial tension.The mechanisms that cause
      different cells to segregate into distinct tissues are unclear. Here the authors
      show in Xenopus that formation of a boundary between two tissues is driven by
      local tension along the interface rather than by global differences in adhesion
      or cortical contractility.

PMID- 28761158
TI  - Determination of the energy band gap of Bi2Se3.
AB  - Despite intensive investigations of Bi2Se3 in past few years, the size and nature
      of the bulk energy band gap of this well-known 3D topological insulator still
      remain unclear. Here we report on a combined magneto-transport, photoluminescence
      and infrared transmission study of Bi2Se3, which unambiguously shows that the
      energy band gap of this material is direct and reaches E g  = (220 +/- 5) meV at
      low temperatures.

PMID- 28761159
TI  - Anti-Fouling Double-Skinned Forward Osmosis Membrane with Zwitterionic Brush for
      Oily Wastewater Treatment.
AB  - Despite its attractive features for energy saving separation, the performance of
      forward osmosis (FO) has been restricted by internal concentration polarization
      and fast fouling propensity that occur in the membrane sublayer. These problems
      have significantly affected the membrane performance when treating highly
      contaminated oily wastewater. In this study, a novel double-skinned FO membrane
      with excellent anti-fouling properties has been developed for emulsified oil
      water treatment. The double-skinned FO membrane comprises a fully porous sublayer
      sandwiched between a highly dense polyamide (PA) layer for salt rejection and a
      fairly loose dense bottom zwitterionic layer for emulsified oil particle removal.
      The top dense PA layer was synthesized via interfacial polymerization meanwhile
      the bottom layer was made up of a zwitterionic polyelectrolyte brush - (poly(3-(N
      2-methacryloxyethyl-N,N-dimethyl) ammonatopropanesultone), abbreviated as PMAPS
      layer. The resultant double-skinned membrane exhibited a high water flux of 13.7
      +/- 0.3 L/m2.h and reverse salt transport of 1.6 +/- 0.2 g/m2.h under FO mode
      using 2 M NaCl as the draw solution and emulsified oily solution as the feed. The
      double-skinned membrane outperforms the single-skinned membrane with much lower
      fouling propensity for emulsified oil-water separation.

PMID- 28761160
TI  - Initial pulse of Siberian Traps sills as the trigger of the end-Permian mass
      extinction.
AB  - Mass extinction events are short-lived and characterized by catastrophic
      biosphere collapse and subsequent reorganization. Their abrupt nature
      necessitates a similarly short-lived trigger, and large igneous province
      magmatism is often implicated. However, large igneous provinces are long-lived
      compared to mass extinctions. Therefore, if large igneous provinces are an
      effective trigger, a subinterval of magmatism must be responsible for driving
      deleterious environmental effects. The onset of Earth's most severe extinction,
      the end-Permian, coincided with an abrupt change in the emplacement style of the
      contemporaneous Siberian Traps large igneous province, from dominantly flood
      lavas to sill intrusions. Here we identify the initial emplacement pulse of
      laterally extensive sills as the critical deadly interval. Heat from these sills
      exposed untapped volatile-fertile sediments to contact metamorphism, likely
      liberating the massive greenhouse gas volumes needed to drive extinction. These
      observations suggest that large igneous provinces characterized by sill complexes
      are more likely to trigger catastrophic global environmental change than their
      flood basalt- and/or dike-dominated counterparts.Although the mass end-Permian
      extinction is linked to large igneous provinces, its trigger remains unclear.
      Here, the authors propose that the abrupt change from flood lavas to sills
      resulted in the heating of sediments and led to the release of large-scale
      greenhouse gases to drive the end-Permian extinction.

PMID- 28761161
TI  - Mitigation of a nitrate reducing Pseudomonas aeruginosa biofilm and anaerobic
      biocorrosion using ciprofloxacin enhanced by D-tyrosine.
AB  - Pseudomonas aeruginosa (PA) is a ubiquitous microbe. It can form recalcitrant
      biofilms in clinical and industrial settings. PA biofilms cause infections in
      patients. They also cause biocorrosion of medical implants. In this work, D
      tyrosine (D-tyr) was investigated as an antimicrobial enhancer for ciprofloxacin
      (CIP) against a wild-type PA biofilm (strain PAO1) on C1018 carbon steel in a
      strictly anaerobic condition. Seven-day biofilm prevention test results
      demonstrated that 2 ppm (w/w) D-tyr enhanced 30 ppm CIP by achieving extra 2-log
      sessile cell reduction compared with the 30 ppm CIP alone treatment. The cocktail
      of 30 ppm CIP + 2 ppm D-tyr achieved similar efficacy as the 80 ppm CIP alone
      treatment in the biofilm prevention test. Results also indicated that the
      enhanced antimicrobial treatment reduced weight loss and pitting corrosion. In
      the 3-hour biofilm removal test, the cocktail of 80 ppm CIP + 5 ppm D-tyr
      achieved extra 1.5-log reduction in sessile cell count compared with the 80 ppm
      CIP alone treatment. The cocktail of 80 ppm CIP + 5 ppm D-tyr achieved better
      efficacy than the 150 ppm CIP alone treatment in the biofilm removal test.

PMID- 28761162
TI  - Hearables: Multimodal physiological in-ear sensing.
AB  - Future health systems require the means to assess and track the neural and
      physiological function of a user over long periods of time, and in the community.
      Human body responses are manifested through multiple, interacting modalities -
      the mechanical, electrical and chemical; yet, current physiological monitors
      (e.g. actigraphy, heart rate) largely lack in cross-modal ability, are
      inconvenient and/or stigmatizing. We address these challenges through an
      inconspicuous earpiece, which benefits from the relatively stable position of the
      ear canal with respect to vital organs. Equipped with miniature multimodal
      sensors, it robustly measures the brain, cardiac and respiratory functions.
      Comprehensive experiments validate each modality within the proposed earpiece,
      while its potential in wearable health monitoring is illustrated through case
      studies spanning these three functions. We further demonstrate how combining data
      from multiple sensors within such an integrated wearable device improves both the
      accuracy of measurements and the ability to deal with artifacts in real-world
      scenarios.

PMID- 28761165
TI  - Broadband tunable integrated CMOS pulser with 80-ps minimum pulse width for gain
      switched semiconductor lasers.
AB  - High power pulsed lasers with tunable pulse widths are highly favored in many
      applications. When combined with power amplification, gain-switched semiconductor
      lasers driven by broadband tunable electric pulsers can meet such requirements.
      For this reason, we designed and produced a low-cost integrated CMOS pulse
      generator with a minimum pulse width of 80 ps and a wide tuning range of up to
      270 ns using a 40-nm microelectronic process technique. We used this pulser to
      drive a 1.3-um semiconductor laser diode directly, and thereafter investigated
      the gain-switching properties of the laser system. The optical pulses consist of
      a spike followed by a steady state region. Tuning the width of the electrical
      pulse down to approximately 1.5 ns produces optical pulses consisting only of the
      spike, which has a minimum pulse-width of 100 ps. Moreover, the duration of the
      steady state can be tuned continuously by tuning the electrical pulse width, with
      a peak power of approximately 5 mW. The output voltage of the electric pulser has
      a tuning range of 0.8-1.5 V that can be used to directly drive semiconductor
      laser diodes with wavelengths in the near-infrared spectrum, which are suitable
      for power amplification with rare-earth doped fiber amplifiers.

PMID- 28761163
TI  - The basal translation rate of authentic HIV-1 RNA is regulated by 5'UTR nt
      pairings at junction of R and U5.
AB  - The paradigm protein synthesis rate is regulated by structural complexity of the
      5'untranslated region (UTR) derives from bacterial and other riboswitches. In
      solution, HIV-1 5'UTR forms two interchangeable long-range nucleotide (nt) 
      pairings, one sequesters the gag start codon promoting dimerization while the
      other sequesters the dimer initiation signal preventing dimerization. While the
      effect of these nt-pairings on dimerization and packaging has been documented
      their effect on authentic HIV translation in cellulo has remained elusive until
      now. HIVNL4-3 5'UTR substitutions were designed to individually stabilize the
      dimer-prone or monomer-prone conformations, validated in-solution, and introduced
      to molecular clones. The effect of 5'UTR conformation on ribosome loading to HIV
      unspliced RNA and rate of Gag polypeptide synthesis was quantified in cellulo.
      Monomer- and dimer-prone 5'UTRs displayed equivalent, basal rate of translation.
      Gain-of-function substitution U103, in conjunction with previously defined nt
      pairings that reorient AUG to flexible nt-pairing, significantly activated the
      translation rate, indicating the basal translation rate is under positive
      selection. The observed translation up-mutation focuses attention to nt-pairings
      at the junction of R and U5, a poorly characterized structure upstream of the
      characterized HIV riboswitch and demonstrates the basal translation rate of
      authentic HIV RNA is regulated independently of monomer:dimer equilibrium of the
      5'UTR.

PMID- 28761164
TI  - Identification of reference genes for qRT-PCR in granulosa cells of healthy women
      and polycystic ovarian syndrome patients.
AB  - Comparative gene expression analysis by qRT-PCR is commonly used to detect
      differentially expressed genes in studies of PCOS pathology. Impaired GC function
      is strongly associated with PCOS pathogenesis, and a growing body of studies has
      been dedicated to identifying differentially expressed genes in GCs in PCOS
      patients and healthy women by qRT-PCR. It is necessary to validate the expression
      stability of the selected reference genes across the tested samples for target
      gene expression normalization. We examined the variability and stability of
      expression of the 15 commonly used reference genes in GCs from 44 PCOS patients
      and 45 healthy women using the GeNorm, BestKeeper, and NormFinder statistical
      algorithms. We combined the rankings of the three programs to produce a final
      ranking based on the geometric means of their stability scores. We found that
      HPRT1, RPLP0, and HMBS out of 15 examined commonly used reference genes are
      stably expressed in GCs in both controls and PCOS patients and can be used for
      normalization in gene expression profiling by qRT-PCR. Future gene-expression
      studies should consider using these reference genes in GCs in PCOS patients for
      more accurate quantitation of target gene expression and data interpretation.

PMID- 28761166
TI  - Anti-centromere antibody exhibits specific distribution levels among anti-nuclear
      antibodies and may characterize a distinct subset in rheumatoid arthritis.
AB  - Anti-centromere antibody (ACA) is one of the classical anti-nuclear antibody
      (ANA) staining patterns. However, characteristics of ACA in comparison with the
      other ANA patterns and clinical features of ACA-positive subjects have not been
      elucidated. Here, we examined all ANA patterns by indirect immunofluorescence for
      859 rheumatoid arthritis (RA) patients. Together with the ANA data of 9,575
      healthy volunteers, we compared distributions of the ANA levels. ACA was the only
      ANA that demonstrated a definite bimodal distribution of levels. ACA showed
      significantly higher levels than the other ANA staining patterns in both RA and
      healthy population (p < 0.0001). ACA-positivity was associated with old age and
      was observed more in females. We further recruited another cohort of 3,353 RA
      patients and confirmed the findings. ACA was also associated with Raynaud's
      phenomenon (p = 6.8 * 10-11) in RA. As a conclusion, ACA displays a specific ANA
      staining pattern with a bimodal distribution, and ACA-positive RA may constitute
      a distinct subset with specific clinical features.

PMID- 28761167
TI  - Functional Detection of TNF Receptor Family Members by Affinity-Labeled Ligands.
AB  - Aberrant expression of TNF family of cytokines has been linked to human diseases,
      and biologics targeting their signaling have become the best selling drugs
      globally. However, functional detection with labeled ligands for accurate
      detection of TNFR family of receptor-expressing target tissues or cell types
      remains to be developed. Here we show that TNF receptor family members are heat
      stable and can be recognized both in vitro and in vivo by their ligands labeled
      with alkaline phosphatase. Such an approach may be used in lieu of antibodies for
      the identification of the cell types involved in receptor signaling during
      disease onset and progression.

PMID- 28761168
TI  - YAP activates the Hippo pathway in a negative feedback loop.

PMID- 28761169
TI  - RIPped for neuroinflammation.

PMID- 28761171
TI  - Genomewide Analysis of Clp1 Function in Transcription in Budding Yeast.
AB  - In budding yeast, the 3' end processing of mRNA and the coupled termination of
      transcription by RNAPII requires the CF IA complex. We have earlier demonstrated
      a role for the Clp1 subunit of this complex in termination and promoter
      associated transcription of CHA1. To assess the generality of the observed
      function of Clp1 in transcription, we tested the effect of Clp1 on transcription
      on a genomewide scale using the Global Run-On-Seq (GRO-Seq) approach. GRO-Seq
      analysis showed the polymerase reading through the termination signal in the
      downstream region of highly transcribed genes in a temperature-sensitive mutant
      of Clp1 at elevated temperature. No such terminator readthrough was observed in
      the mutant at the permissive temperature. The poly(A)-independent termination of
      transcription of snoRNAs, however, remained unaffected in the absence of Clp1
      activity. These results strongly suggest a role for Clp1 in poly(A)-coupled
      termination of transcription. Furthermore, the density of antisense transcribing
      polymerase upstream of the promoter region exhibited an increase in the absence
      of Clp1 activity, thus implicating Clp1 in promoter directionality. The overall
      conclusion of these results is that Clp1 plays a general role in poly(A)-coupled
      termination of RNAPII transcription and in enhancing promoter directionality in
      budding yeast.

PMID- 28761170
TI  - Intravenous infusion of human bone marrow mesenchymal stromal cells promotes
      functional recovery and neuroplasticity after ischemic stroke in mice.
AB  - Transplantation of human bone marrow mesenchymal stromal cells (hBM-MSC) promotes
      functional recovery after stroke in animal models, but the mechanisms underlying
      these effects remain incompletely understood. We tested the efficacy of Good
      Manufacturing Practices (GMP) compliant hBM-MSC, injected intravenously 3.5 hours
      after injury in mice subjected to transient middle cerebral artery occlusion
      (tMCAo). We addressed whether hBM-MSC are efficacious and if this efficacy is
      associated with cortical circuit reorganization using neuroanatomical analysis of
      GABAergic neurons (parvalbumin; PV-positive cells) and perineuronal nets (PNN), a
      specialized extracellular matrix structure which acts as an inhibitor of neural
      plasticity. tMCAo mice receiving hBM-MSC, showed early and lasting improvement of
      sensorimotor and cognitive functions compared to control tMCAo mice. Furthermore,
      5 weeks post-tMCAo, hBM-MSC induced a significant rescue of ipsilateral cortical
      neurons; an increased proportion of PV-positive neurons in the perilesional
      cortex, suggesting GABAergic interneurons preservation; and a lower percentage of
      PV-positive cells surrounded by PNN, indicating an enhanced plastic potential of
      the perilesional cortex. These results show that hBM-MSC improve functional
      recovery and stimulate neuroprotection after stroke. Moreover, the downregulation
      of "plasticity brakes" such as PNN suggests that hBM-MSC treatment stimulates
      plasticity and formation of new connections in the perilesional cortex.

PMID- 28761172
TI  - Acute ocular hypertension disrupts barrier integrity and pump function in rat
      corneal endothelial cells.
AB  - Acute ocular hypertension (AOH) frequently compromises corneal endothelial cell
      (CEC) function in clinical practice. This type of stress induces corneal oedema
      and a decrease in the corneal endothelial cell density (ECD). The anterior
      chamber of the right eye of Sprague-Dawley rats was irrigated with Balanced Salt
      Solution (BSS) for two hours, and the left eye served as a control to determine
      the time-dependent effects of AOH on endothelial cell morphology and function.
      The average intraocular pressure (IOP) increased to 82.6 +/- 2.3 mmHg (normal
      range: 10.2 +/- 0.4 mmHg) during anterior irrigation. Very soon after initiating
      irrigation, corneal oedema became evident and the cornea exhibited a significant
      increase in permeability to FITC-dextran. The peripheral ECD was significantly
      reduced, and the morphology of CECs became irregular and multiform. The
      structures of the zonula occludens-1 (ZO-1) and F-actin were severely disrupted.
      In addtion, Na,K-ATPase exhibited a dispersed expression pattern. Two days after
      irrigation, obvious CEC proliferation was observed, the ECD recovered to a normal
      level, and F-actin was dispersed throughout the cytoplasm. Seven days later, the
      CEC structure and function were nearly normalized. Based on the results obtained
      using this model, an acute IOP crisis exerts transient deleterious effects on CEC
      structure and function in rats.

PMID- 28761173
TI  - J e (4.2 K, 31.2 T) beyond 1 kA/mm2 of a ~3.2 MUm thick, 20 mol% Zr-added MOCVD
      REBCO coated conductor.
AB  - A main challenge that significantly impedes REBa2Cu3Ox (RE = rare earth) coated
      conductor applications is the low engineering critical current density J e
      because of the low superconductor fill factor in a complicated layered structure
      that is crucial for REBa2Cu3Ox to carry supercurrent. Recently, we have
      successfully achieved engineering critical current density beyond 2.0 kA/mm2 at
      4.2 K and 16 T, by growing thick REBa2Cu3Ox layer, from ~1.0 MUm up to ~3.2 MUm,
      as well as controlling the pinning microstructure. Such high engineering critical
      current density, the highest value ever observed so far, establishes the
      essential role of REBa2Cu3Ox coated conductors for very high field magnet
      applications. We attribute such excellent performance to the dense c-axis self
      assembled BaZrO3 nanorods, the elimination of large misoriented grains, and the
      suppression of big second phase particles in this ~3.2 MUm thick REBa2Cu3Ox film.

PMID- 28761174
TI  - Electronic structure and its external electric field modulation of PbPdO2
      ultrathin slabs with (002) and (211) preferred orientations.
AB  - The Electronic structure of PbPdO2 with (002) and (211) preferred orientations
      were investigated using first-principles calculation. The calculated results
      indicate that, (002) and (211) orientations exhibit different electric field
      dependence of band-gap and carrier concentration. The small band gap and more
      sensitive electric field modulation of band gap were found in (002) orientation.
      Moreover, the electric field modulation of the resistivity up to 3-4 orders of
      magnitude is also observed in (002) slab, which reveals that origin of colossal
      electroresistance. Lastly, electric field modulation of band gap is well
      explained. This work should be significant for repeating the colossal
      electroresistance.

PMID- 28761176
TI  - Control of pattern formation during phase separation initiated by a propagated
      trigger.
AB  - Understanding pattern formation during phase separation is a key topic in
      materials science for the important role that patterns play in determining
      macroscopic physical properties. In this work, we show how pattern formation can
      be controlled using a phase-separation trigger propagating outwards from a point.
      We found a range of patterns, including a random droplet pattern, a concentric
      pattern and a dendritic pattern, depending on the speed at which the trigger
      propagates, while only the random droplet pattern is observed in a system with
      homogeneous cooling. We also found that the phase at the core of the concentric
      pattern periodically changes with time. In addition, we investigated pattern
      formation during phase separation induced by multiple propagated triggers. When
      we propagate the triggers from periodic points in space, a metastable regular
      hexagonal pattern is formed. We also found a bifurcation between a case where the
      majority phase becomes a droplet phase and a case where the minority phase adopts
      a droplet pattern. We also confirm the existence of a percolated, bicontinuous
      phase, even with an asymmetric composition.

PMID- 28761175
TI  - ROCK1 is a novel Rac1 effector to regulate tubular endocytic membrane formation
      during clathrin-independent endocytosis.
AB  - Clathrin-dependent and -independent pathways contribute for beta1-integrin
      endocytosis. This study defines a tubular membrane clathrin-independent endocytic
      network, induced with the calmodulin inhibitor W13, for beta1-integrin
      internalization. This pathway is dependent on increased phosphatidylinositol 4,5
      bisphosphate (PI(4,5)P2) levels and dynamin activity at the plasma membrane.
      Exogenous addition of PI(4,5)P2 or phosphatidylinositol-4-phosphate 5-kinase
      (PIP5K) expression mimicked W13-generated-tubules which are inhibited by active
      Rac1. Therefore, the molecular mechanisms downstream of Rac1, that controls this
      plasma membrane tubulation, were analyzed biochemically and by the expression of
      different Rac1 mutants. The results indicate that phospholipase C and ROCK1 are
      the main Rac1 effectors that impair plasma membrane invagination and tubule
      formation, essentially by decreasing PI(4,5)P2 levels and promoting cortical
      actomyosin assembly respectively. Interestingly, among the plethora of proteins
      that participate in membrane remodeling, this study revealed that ROCK1, the well
      known downstream RhoA effector, has an important role in Rac1 regulation of
      actomyosin at the cell cortex. This study provides new insights into Rac1
      functioning on plasma membrane dynamics combining phosphatidylinositides and
      cytoskeleton regulation.

PMID- 28761177
TI  - Analysis of autophagy gene polymorphisms in Spanish patients with head and neck
      squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth cancer on incidence
      worldwide. Tobacco and alcohol consumption are the most classical risk factors
      associated with its development. Autophagy process has a dual effect both in
      tumourigenesis and tumour suppressing activity. To investigate the importance of
      this pathway in HNSCC susceptibility, a risk factor matched case-control
      association study was performed with four candidate polymorphisms in autophagy
      genes (ATG2B, ATG5, ATG10, ATG16L1). We found an association between the variant
      in ATG10 rs1864183 and a higher susceptibility to develop laryngeal cancer, ATG2B
      rs3759601 and pharyngeal cancer and ATG16L1 rs2241880 and oral carcinoma. ATG5
      rs2245214 SNP was not associated with any location. Overall, our results indicate
      the importance of the autophagy pathway in the susceptibility of head and neck
      squamous cell carcinoma and demonstrate the heterogeneity between its locations
      encompassed under a single terminology.

PMID- 28761178
TI  - Heterodera schachtii Tyrosinase-like protein - a novel nematode effector
      modulating plant hormone homeostasis.
AB  - The beet cyst nematode Heterodera schachtii causes major yield losses in sugar
      beet. Understanding the interaction between H. schachtii and its host plant is
      important for developing a sustainable management system. Nematode effectors play
      a crucial role in initializing and sustaining successful parasitism. In our
      study, we identified a gene (Hs-Tyr) encoding a tyrosinase functional domain
      (PF00264). We describe Hs-Tyr as a novel nematode effector. Hs-Tyr is localized
      in the nematode esophageal gland. Up-regulation of its expression coincided with
      the parasitic developmental stages of the nematode. Silencing Hs-Tyr by RNA
      interference made the treated nematodes less virulent. When RNAi-treated
      nematodes succeeded in infecting the plant, developing females and their
      associated syncytial nurse cells were significantly smaller than in control
      plants. Ectopically expressing the Hs-Tyr effector in Arabidopsis increased plant
      susceptibility to H. schachtii, but not to the root-knot nematode Meloidogyne
      incognita. Interestingly, Hs-Tyr in the plant promoted plant growth and changed
      the root architecture. Additionally, the expression of Hs-Tyr in Arabidopsis
      caused changes in the homeostasis of several plant hormones especially auxin and
      the ethylene precursor aminocyclopropane-carboxylic acid.

PMID- 28761179
TI  - Soluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced
      Adventitial Remodeling.
AB  - Epoxyeicosatrienoic acids (EETs), the metabolites of cytochrome P450 epoxygenases
      derived from arachidonic acid, exert important biological activities in
      maintaining cardiovascular homeostasis. Soluble epoxide hydrolase (sEH)
      hydrolyzes EETs to less biologically active dihydroxyeicosatrienoic acids.
      However, the effects of sEH inhibition on adventitial remodeling remain
      inconclusive. In this study, the adventitial remodeling model was established by
      continuous Ang II infusion for 2 weeks in C57BL/6 J mice, before which sEH
      inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was
      administered by gavage. Adventitial remodeling was evaluated by histological
      analysis, western blot, immunofluorescent staining, calcium imaging, CCK-8 and
      transwell assay. Results showed that Ang II infusion significantly induced vessel
      wall thickening, collagen deposition, and overexpression of alpha-SMA and PCNA in
      aortic adventitia, respectively. Interestingly, these injuries were attenuated by
      TPPU administration. Additionally, TPPU pretreatment overtly prevented Ang II
      induced primary adventitial fibroblasts activation, characterized by
      differentiation, proliferation, migration, and collagen synthesis via Ca2+
      calcineurin/NFATc3 signaling pathway in vitro. In summary, our results suggest
      that inhibition of sEH could be considered as a novel therapeutic strategy to
      treat adventitial remodeling related disorders.

PMID- 28761180
TI  - Iterative reconstruction improves detection of in-stent restenosis by high-pitch
      dual-source coronary CT angiography.
AB  - Recent studies demonstrated that sinogram affirmed iterative reconstructions
      (SAFIRE) can produce higher-resolution images with greater robustness for the
      reduction of various imaging artefacts. Eighty-five patients were prospectively
      evaluated and underwent a high-pitch spiral acquisition CT scan. In-stent noise,
      signal-to-noise ratio(SNR), stent-lumen attenuation increase ratio (SAIR), and
      subjective image quality score were measured and compared between the SAFIRE and
      Filter back projection (FBP) reconstructions. Conventional coronary angiography
      served as the standard of reference. In 159 evaluated stents, SAFIRE was superior
      to FBP with regards to in-stent noise, SNR, SAIR, and image quality score. On per
      stent analysis, SAFIRE vs. FBP reconstruction yielded 85% vs. 85%sensitivity, 89%
      vs. 78%specificity, 73% vs. 57%positive predictive value, 95% vs. 94%negative
      predictive value, and 0.87 vs. 0.82 area under curve, although these improvements
      did not reach statistical significance (P > 0.05). However, in the subgroup of
      small diameter stents (<=3 mm; n = 95), specificity(82% vs. 62%), positive
      predictive value(66% vs. 50%) and area under curve (0.81 vs. 0.70) improved
      significantly (P < 0.05) with SAFIRE. SAFIRE image reconstruction can thus
      improve the evaluation for ISR, especially in smaller stents.

PMID- 28761182
TI  - Ethical question of the month - August 2017.

PMID- 28761181
TI  - Brachycephalic dogs - time for action.

PMID- 28761183
TI  - Canada: Serotyping of Haemophilus parasuis field isolates from diseased pigs in
      Quebec by indirect hemagglutination assay and multiplex polymerase chain reaction
      (PCR).

PMID- 28761184
TI  - Agreement among undergraduate and graduate veterinary students and veterinary
      anesthesiologists on pain assessment in cats and dogs: A preliminary study.
AB  - This study investigated agreement among undergraduate and graduate veterinary
      students and veterinary anesthesiologists on video pain assessment at the
      University of Montreal. Pain assessment in dogs and cats appeared to be affected
      by gender, previous experience, and degree of training despite a small population
      of observers.

PMID- 28761186
TI  - Blood lactate concentration in diabetic dogs.
AB  - Human diabetic patients may have increased lactate levels compared to non
      diabetics. Despite the use of lactate levels in critical care assessment,
      information is lacking for diabetic dogs. Therefore, this prospective cross
      sectional clinical study aimed to determine lactate concentrations in 75 diabetic
      dogs [25 newly diagnosed non-ketotic diabetics, 25 under insulin treatment, and
      25 in diabetic ketoacidosis (DKA)], compared to 25 non-diabetic dogs. Lactate
      levels (mmol/L) were not different among groups (P = 0.20); median and 25th to
      75th percentile were 2.23 and P25-75 = 1.46 to 2.83 for controls, 1.69 and P25-75
      = 1.09 to 2.40 for newly diagnosed non-ketotic diabetics, 2.27 and P25-75 = 1.44
      to 2.90 for dogs under insulin treatment for at least 30 days, and 2.40 and P25
      75 = 1.58 to 3.01 for dogs in DKA. Longitudinal studies assessing both isomers (L
      and D-lactate) are needed to better elucidate the role of lactate in the
      pathophysiology of diabetes acid-base status in dogs.

PMID- 28761187
TI  - Response to acupuncture treatment in horses with chronic laminitis.
AB  - There is a need for evidence-based scientific research to address the question of
      the effectiveness of acupuncture in improving clinical signs of laminitis in
      horses. The objective of this study was to compare lameness levels before and
      after 2 acupuncture treatments in horses with chronic laminitis. Twelve adult
      horses with chronic laminitis received 2 acupuncture treatments 1 week apart. The
      points were treated using dry needling, hemo-acupuncture, and aqua-acupuncture.
      Lameness level was objectively evaluated using an inertial sensor-based lameness
      evaluation system (Lameness Locator), as well as routine examinations following
      American Association of Equine Practitioners scoring before the first and 1 week
      after the second acupuncture treatment. Data were analyzed using Wilcoxon signed
      rank test and P-values < 0.05 were considered statistically significant. Both the
      Lameness Locator (P = 0.0269) and routine lameness examination (P = 0.0039)
      showed a significant reduction in lameness severity. Our results support using
      acupuncture, along with other treatment options, in treating chronic equine
      laminitis.

PMID- 28761185
TI  - Comparative efficacy of intranasal and injectable vaccines in stimulating
      Bordetella bronchiseptica-reactive anamnestic antibody responses in household
      dogs.
AB  - In order to determine the comparative efficacy of injectable and intranasal
      vaccines to stimulate Bordetella bronchiseptica (Bb)-reactive anamnestic
      antibodies, a trial was conducted using 144 adult household dogs of various
      breeds and ages, which had been previously administered intranasal Bb vaccine
      approximately 12 months before enrollment. Dogs were randomized into 2 groups and
      blood, nasal swabs, and pharyngeal swabs were collected prior to the
      administration of single component Bb vaccines intranasally or parenterally. Ten
      to 14 days later all dogs were resampled to measure changes in systemic and local
      antibody to Bb. There were no differences in the changes in Bb-reactive serum IgG
      and nasal IgA between the groups, whereas intranasally vaccinated dogs had
      significantly higher Bb-reactive serum IgA. These data indicate that both of the
      current generation of intranasal (modified-live) and injectable (acellular) Bb
      vaccines can stimulate anamnestic local and systemic antibody responses in
      previously vaccinated, Bb-seropositive adult household dogs.

PMID- 28761188
TI  - Flock-level prevalence, geographical distribution, and seasonal variation of
      avian reovirus among broiler flocks in Ontario.
AB  - Avian reovirus (ARV) is an economically significant pathogen of broiler chickens.
      Our objective was to determine the prevalence, geographical distribution, and
      seasonal variation of ARV infection among commercial broiler flocks in Ontario,
      Canada during grow-out. A cross-sectional study of 231 randomly selected flocks
      was conducted from July 2010 to January 2012. Fifteen blood samples, 15 whole
      intestines, and 15 cloacal swabs per flock were collected at slaughter; ELISA and
      PCR were used to determine a flock's ARV exposure status. Avian reovirus
      prevalence was 91% (95% CI: 87 to 94). District alone did not significantly
      explain the overall variation in the prevalence of ARV (univariable logistic
      regression; P = 0.073), although geographical differences were identified. The
      odds of ARV presence were significantly lower in the summer/autumn compared to
      the winter/spring (univariable exact logistic regression; P < 0.001). There was
      no association between flock mortality and flock ELISA mean titer or PCR status.

PMID- 28761189
TI  - Use of skin stretching techniques before bilateral caudal superficial epigastric
      axial flaps in a dog with severe burns.
AB  - This report describes how 2 days of skin stretching facilitated a tension-free
      closure of single event bilateral caudal superficial epigastric flaps in a dog
      with severe hindquarter burns. Full healing at all surgical sites with only minor
      dehiscence and without further treatment or abnormalities of gait or coat
      regrowth was achieved.

PMID- 28761190
TI  - Meningeal dissemination of a pituitary carcinoma to the cauda equina in a dog.
AB  - An 8-year-old spayed female border collie dog was diagnosed with an invasive
      pituitary macrotumor. Five months after radiation therapy, the patient developed
      paraparesis and lumbosacral pain. Necropsy revealed a pituitary carcinoma with
      cauda equina drop metastasis. In cases of pituitary masses, meningeal
      dissemination should be considered if neurologic status declines.

PMID- 28761191
TI  - Cecal entrapment within the epiploic foramen in a mare.
AB  - An 11-year-old Thoroughbred mare with colic unresponsive to medical treatment
      underwent exploratory laparotomy. During surgery the cecum was found entrapped
      within the epiploic foramen from left to right. The entrapped cecum was reduced
      through the foramen by gentle traction. After reduction of the cecum, rupture of
      the portal vein was detected. Loss of a large amount of blood prompted euthanasia
      during surgery.

PMID- 28761192
TI  - Outcome of prolonged acute vena cava occlusion after iatrogenic transection and
      repair in a dog.
AB  - A 12-year-old castrated male Airedale terrier dog was diagnosed with a
      hepatocellular carcinoma in the right medial liver lobe. During tumor resection,
      inadvertent stapling and transection of the caudal vena cava occurred. Complete
      caval occlusion was required for 18 minutes and primary anastomosis was
      completed. The dog received 2 blood transfusions and developed mild pelvic limb
      edema after surgery. Computed tomography evaluation 9 months after surgery showed
      collateral circulation and suspected stricture of the vena cava with an absence
      of clinical effect. The dog remained alive and asymptomatic more than 1 year
      after surgery.

PMID- 28761193
TI  - Intranasal mast cell tumor in the dog: A case series.
AB  - The medical records of 4 dogs with histologically confirmed intranasal mast cell
      tumors (MCTs) were retrospectively evaluated to determine their biological
      behavior. Information on signalment, presenting clinical signs, tumor grade,
      treatment administered, and survival times was obtained from the medical record.
      All 4 patients had high grade tumors and received chemotherapy. Survival times
      ranged from 27 to 134 days. All 4 dogs showed signs of local or distant disease
      progression, suggestive of an aggressive behavior of intranasal MCTs.

PMID- 28761194
TI  - Spontaneous resorption of a herniated cervical disc in a dog detected by magnetic
      resonance imaging.
AB  - This report describes, for the first time in small animal literature, the
      spontaneous resorption of herniated Hansen type I intervertebral disc material in
      the cervical spine of a chondrodystrophic dog over a 4-month period, documented
      by magnetic resonance imaging. Clinical signs (cervical hyperpathia) responded to
      conservative treatment during the same period.

PMID- 28761195
TI  - The eradication of bovine tuberculosis in Canada.

PMID- 28761196
TI  - Dimensions of wellness: Change your habits, change your life.

PMID- 28761197
TI  - Establishing self-confidence through learned knowledge.

PMID- 28761198
TI  - Communication: Touchy at-home treatment communication dilemmas.

PMID- 28761199
TI  - A Narrative Review of Acute Adult Poisoning in Iran.
AB  - Poisoning is a frequent cause of referral to medical emergencies and a major
      health problem around the world, especially in developing countries. We aimed to
      review the epidemiology and pattern of adult poisoning in Iran in order to
      facilitate the early diagnosis and management of poisoning. The pattern of
      poisoning is different in various parts of Iran. Pharmaceutical compounds were
      the most common cause of poisoning in most parts of Iran. Pesticide-related
      toxicities were more common in northern agricultural regions, whereas bites and
      stings were seen more commonly in southern Iran. Carbon monoxide poisoning was
      common in cities with many motor vehicles such as Tehran and in colder climates
      such as in northern and western regions due to inadequately vented gas appliances
      such as stoves and heaters. Majoon Birjandi (containing cannabis) is a unique
      substance used in eastern Iran. Poisoning by opioids, tramadol, and pesticides
      (organophosphate and aluminum phosphide) has remained a common hazard in Iran.
      Poisoning-associated morbidity and mortality rates vary by region and have
      changed over time due to the introduction of new drugs and chemicals. Early
      diagnosis and proper treatment may be lifesaving; thus, understanding the general
      pattern of poisoning in different regions is important.

PMID- 28761200
TI  - A Prospective Study of Altered Inflammatory Response and Its Clinical Outcome
      following Laparoscopic and Open Cholecystectomy.
AB  - BACKGROUND: Inflammatory response following surgical trauma has long been a
      matter of study. Results, however, have been varied. We sought to assess changes
      in the levels of proinflammatory and anti-inflammatory cytokines in patients
      undergoing laparoscopic and open cholecystectomy and their impact on the clinical
      outcome of patients concerning the postoperative pain score. METHODS: The study
      involved 90 cholecystectomies (55 laparoscopic and 35 open) for chronic
      cholecystitis. Blood samples were collected 2 hours preoperatively and at 4 and
      24 hours post surgery. Sera were evaluated for the levels of interleukin-1beta,
      interleukin-10, and tumor necrosis factor-alpha. The independent sample t-test
      was used to compare the means of a variable between the 2 groups. Statistical
      analysis was done using SPSS, version 17. RESULTS: The rise in the levels of
      interleukin-1beta, interleukin-10, and tumor necrosis factor-alpha was
      significantly more in the open cholecystectomy group at 4 hours (P<0.00). At the
      24th postoperative hour, the levels of all 3 cytokines were also higher in the
      open cholecystectomy group (P<0.001 for interleukin-1beta, P=0.185 for
      interleukin-10, and P<0.001 for tumor necrosis factor-alpha). At the 4th
      postoperative hour, the patients in the laparoscopic cholecystectomy group had a
      significantly lower pain score (P<0.001) than the open group. CONCLUSION: Both
      laparoscopic and open cholecystectomy procedures altered the inflammatory milieu
      of our patients in the postoperative period. Inflammation caused by the
      laparoscopic procedure was significantly less. More research is needed to target
      specific inflammatory and anti-inflammatory cytokines to reduce surgical stress
      and improve patient outcomes.

PMID- 28761201
TI  - The Impact of Methylphenidate on Motor Performance in Children with both
      Attention Deficit Hyperactivity Disorder and Developmental Coordination Disorder:
      A Randomized Double-Blind Crossover Clinical Trial.
AB  - BACKGROUND: Children with attention deficit hyperactivity disorder/developmental
      coordination disorder (ADHD/DCD) suffer from problems associated with gross and
      fine motor skills. There is no effective pharmacological therapy for such
      patients. We aimed to assess the impact of methylphenidate (MPH) on motor
      performance of children with ADHD/DCD. METHODS: In this double-blind placebo
      controlled, 17 children (12 boys) with ADHD/DCD with a mean age of 7 years 6
      months were recruited in Shafa Hospital, Rasht, Iran. The response was defined as
      >=25% reduction in the total score of ADHD rating scale-IV from the baseline.
      Sixteen boys entered phase 2 of the study in which the impact of MPH on motor
      function was determined through a crossover randomized clinical trial. Eligible
      individuals were scheduled for baseline and two assessment visits after a one
      week period of intervention. We used the short form of Bruininks-Oseretsky test
      (BOT-2) to identify the disability of motor function. Children were randomly
      assigned to receive MPH or inert ingredients (placebo). In the second period,
      medication (MPH/placebo) was crossed over. The effects of MPH were analyzed using
      chi2 test for related samples to compare the performance during baseline,
      placebo, and MPH trials. The results were analyzed using the SPSS software
      version 16.0. RESULTS: The mean minimal effective dose of MPH per day was 17.3 mg
      (0.85 mg/kg). Children with higher ADHD rating scale had a significantly lower
      standard score in BOT-2 (P=0.03). Following MPH intake, 26.6% of the children
      showed clinically significant improvement in motor function. However, the
      improvement was not statistically different between the MPH and placebo.
      CONCLUSION: Although MPH improved ADHD symptoms, problems with motor performance
      still remained. Further work is required to determine the probable effects of MPH
      in a higher dosage or in different subtypes of ADHD. TRIAL REGISTRATION NUMBER:
      IRCT201107071483N2.

PMID- 28761202
TI  - Admission Test and Pregnancy Outcome.
AB  - BACKGROUND: The admission test (AT) has been carried out for many years, but
      there are still debates about the prognostic value of the test. Therefore, we
      aimed to examine the value of the AT in predicting the adverse outcome in
      neonates. METHODS: In this cross-sectional study, 425 pregnant women with normal
      vaginal delivery were studied between2009 and 2014at Vali-e-Asr Hospital. Based
      on the results, the women were divided into 2groups of normal and abnormal ATs.
      All the patients were followed up until the birth of their baby, when the status
      of mother and neonate was determined. The main outcomes of the study were
      cesarean rate, neonatal intensive care unit (NICU) admission, fetus demise,
      neonatal acidosis, and Apgar score. The independent t-test, chi-square test,
      Fisher exact test, and logistic regression were used for statistical analysis.
      The data were analyzed using SPSS (version 17). RESULTS: Of 425 pregnant women
      studied, 142 (33.4%) had abnormal ATs with a mean age of 29 (+/-4.5) years.
      Multivariate analysis showed that an abnormal AT was able to predict the
      incidence of cesarean section, intrauterine growth restriction, turned cord, and
      Apgar<7, but it could not predict neonatal death and hypoxia. CONCLUSION: The AT
      was shown to be a useful screening test with risk factors such as
      oligohydramnios, bloody amniotic fluid, meconium amniotic fluid, intrauterine
      growth restriction, and turned cord. Additionally, the test was also able to
      predict NICU admission and the need for cesarean section, but it could not
      predict the occurrence of neonatal death.

PMID- 28761203
TI  - Inhibitory Effect of Bunium Persicum Hydroalcoholic Extract on Glucose-Induced
      Albumin Glycation, Oxidation, and Aggregation In Vitro.
AB  - BACKGROUND: Glucose-induced protein glycation has been implicated in the
      progression of diabetic complications and age-related diseases. The anti
      glycation potential of polyphenol-rich plant extracts has been shown previously.
      Bunium Persicum has been demonstrated to possess a high level of polyphenols. The
      aim of current in vitro study was to determine the possible inhibitory effect of
      Bunium Persicum hydroalcoholic extract (BPE) on glucose-induced bovine serum
      albumin (BSA) glycation, oxidation, and aggregation. METHODS: Folin-Ciocalteu
      assay was used to measure the content of total phenolic compounds of BPE. To test
      the in vitro effect of BPE on the formation of glycated BSA, thiol group
      oxidation, and protein aggregation of BSA, various concentrations of BPE were
      incubated with BSA and glucose at 37  degrees C for 72 hr. Glycation, thiol group
      oxidation, and aggregation of BSA were then measured using thiobarbituric acid,
      2, 4-dinitrophenylhydrazine, and Congo red colorimetric methods, respectively.
      Data were analyzed using the SPSS software (version 16.0). One-way ANOVA followed
      by Tukey's post hoc test was used to compare group means. P<0.05 was accepted as
      the statistically significant difference between groups. RESULTS: The results
      demonstrated that the content of total phenolics of BPE was 122.41 mg gallic acid
      equivalents per gram dried extract. BPE (10, 15, and 30 MUg/ml) significantly
      inhibited the formation of GA in a concentration-dependent manner. BPE also
      significantly decreased the levels of thiol group oxidation and BSA aggregation.
      CONCLUSION: The results showed that BPE has anti-glycation and antioxidant
      properties and might have therapeutic potentials in the prevention of glycation
      mediated diabetic complications.

PMID- 28761204
TI  - Isolation and Detection of Erysipelothrix rhusiopathiae and Its Distribution in
      Humans and Animals by Phenotypical and Molecular Methods in Ahvaz-Iran in 2015.
AB  - BACKGROUND: Erysipelothrix rhusiopathiae (E. rhusiopathiae) is generally
      transmitted into the gastrointestinal tract of animals by the intake of
      contaminated food or water and causes great economic loss in agriculture
      worldwide. Some of the Erysipelothrix spp. are the causative agents of
      erysipeloid, which is an occupational infection in humans. The aim of the present
      study was to isolate E. rhusiopathiae from animals as well as the hands of the
      butchers working in Ahvaz, Iran, and to determine their susceptibility to
      antibiotics. METHODS: Totally, 150 samples were taken from slaughterhouse
      workers, fishermen, and livers and hearts of sheep and calves by the swabbing
      method. Phenotypical methods and polymerase chain reaction (PCR) were used for
      the isolation and identification of E. rhusiopathiae. The isolates were tested
      for their susceptibility to commonly used antimicrobial agents using the disk
      diffusion protocol described by the Clinical and Laboratory Standards Institute.
      RESULTS: Out of the 150 samples examined via phenotypical and biochemical tests,
      16 samples were positive as putative Erysipelothrix spp. twelve cases out of the
      16 putative Erysipelothrix spp. were confirmed by PCR. The tested isolates were
      highly sensitive to the antibiotics used. The results of the sensitivity and
      specificity of PCR revealed that the sensitivity and specificity of indirect PCR
      were higher than those of direct PCR. CONCLUSION: E. rhusiopathiae is widely
      distributed on seafood and presents as a commensal pathogen in nature and
      animals. Infection with this microorganism should be emphasized because it is a
      rare organism causing severe infections such as infectious endocarditis and
      polyarthritis following localized infections.

PMID- 28761205
TI  - Pain Relief with Wet Cupping Therapy in Rats is Mediated by Heat Shock Protein 70
      and beta-Endorphin.
AB  - BACKGROUND: Wet cupping therapy is a complementary therapy in pain management.
      The mechanism of this therapy, however, needs further elucidation. Cells injured
      by wet cupping therapy seem to stimulate the expression of heat shock protein 70
      (HSP70). Its benefit in pain reduction could be mediated by the expression of
      beta-endorphin. This study aimed at determining the correlation between HSP70 and
      beta-endorphin after wet cupping therapy. METHODS: Sixteen male Wistar rats were
      divided into control (CG; n=8) and treatment (TG; n=8) groups. The rats in both
      groups were injected with complete Freund's adjuvant (CFA) at the footpad. In the
      TG, wet cupping therapy was done at the left and right paralumbar regions 48
      hours after the CFA injection. Twenty-four hours after therapy, the hot plate
      test was done to assess pain threshold. Thereafter, immunohistochemistry from the
      skin subjected to wet cupping therapy was conducted for HSP70 and beta-endorphin.
      RESULTS: The expression of HSP70 was significantly higher in the keratinocytes of
      the TG (20.25+/-3.53; P<0.001) than in the keratinocytes of the CG (10.50+/-2.44;
      P<0.001). The expression of beta-endorphin was significantly higher in the
      keratinocytes of the TG (22.37+/-3.52; P<0.001) than in the keratinocytes of the
      CG (5.12+/-1.72; P<0.001). The results also revealed a high correlation between
      HSP70 and beta-endorphin (beta=0.864; P<0.001). Pain threshold after wet cupping
      therapy was significantly higher in the TG (22.81+/-6.34 s; P=0.003) than in the
      CG (11.78+/-3.56 s). CONCLUSIONS: The benefit of wet cupping therapy in terms of
      pain reduction in rats could be mediated by the expression of HSP70 and beta
      endorphin.

PMID- 28761206
TI  - Comparative Dermatoglyphic Study between Autistic Patients and Normal People in
      Iran.
AB  - Autism is a neurodevelopmental disorder originating from early childhood;
      nevertheless, its diagnosis is in older ages. In addition to heredity,
      environmental factors are also of great significance in the etiology of the
      disease. Dermatoglyphic patterns, albeit varied, remain stable for a lifetime and
      yield a large number of patterns upon examination. Studies have shown a
      significant association between dermatoglyphics and some diseases, especially
      genetic ones. We compared fingerprints between patients with autism and normal
      individuals in a Fars population living in Khorasan-Razavi Province, Iran, in
      2015. The right and left hand fingerprints of 104 autistic individuals (case
      group; age range=5-15 y) were collected using a fingerprint scanner. The same
      process was performed for 102 healthy individuals, in the age range of 6 to 25
      years. All dermatoglyphic patterns and ridge counts were determined. The data
      were analyzed using the Mann-Whitney nonparametric test and binomial
      distribution. There was a significant difference in the distribution of the
      dermatoglyphic patterns on the right and left thumbs and the index fingers
      between the case and control groups (P<0.05). The patients had a significantly
      higher count of loops on their right and left thumbs and their index fingers. A
      significant decrease in ridge counts for the right and left thumbs and the index
      fingers was observed in the patients compared to the controls. The results
      suggested that the patterns were associated with the risk of autism. The patterns
      may be drawn upon as biometric parameters in the screening of children with
      autism.

PMID- 28761207
TI  - Importance of RIFLE (Risk, Injury, Failure, Loss, and End-Stage Renal Failure)
      and AKIN (Acute Kidney Injury Network) in Hemodialysis Initiation and Intensive
      Care Unit Mortality.
AB  - Our study evaluated the differences between early and late hemodialysis (HD)
      initiation in the intensive care unit (ICU) according to the RIFLE (Risk, Injury,
      Failure, Loss, and End-stage renal failure) and AKIN (Acute Kidney Injury
      Network) classifications. On the assumption that early initiation of HD in
      critical patients according to the RIFLE and AKIN criteria decreases mortality,
      we retrospectively evaluated the medical records of 68 patients in our medical
      ICU and divided the patients into 2 groups: Those undergoing HD in no risk, risk,
      or injury stage according to RIFLE and in stage 0, I, or II according to AKIN
      were defined as early HD and those in failure stage according to RIFLE and in
      stage III according to AKIN were defined as late HD. The median age of the
      patients was 66.5 years, and 56.5% were male. HD was started in 25% and 39.7% of
      the patients in the early stage in the RIFLE and AKIN classification,
      respectively. According to RIFLE, HD was started in 61.5% of the surviving
      patients in the early stage; this rate was 16.4% in the deceased patients
      (P=0.001). HD was commenced in 69.2% of the surviving patients in AKIN stages 0,
      I, and II and in 32.7% of the deceased patients (P=0.026). Sepsis (61.5% vs.
      94.5%; P=0.001) and mechanical ventilation (30.8% vs. 87.3%; P<0.001) during HD
      increased ICU mortality, whereas HD initiation in the early stages according to
      RIFLE decreased ICU mortality (61.5% vs. 16.4%; P=0.001). In conclusion, in
      critically ill patients, HD initiation in the early stages according to the RIFLE
      classification decreased our ICU mortality.

PMID- 28761208
TI  - Sudden Bilateral Sensorineural Hearing Loss Following Postpartum Hemorrhage: A
      Case Report.
AB  - The prevalence of bilateral sudden sensorineural hearing loss (SSNHL) is less
      than 5% and the etiology of most cases is unknown. Due to many structural and
      functional similarities between the kidney and inner ear, many conditions,
      diseases, and drugs have both renal and cochlear effects and toxicities. There
      are several reports of SSNHL in patients with CRF, uraemic patient, hemodialysis
      treatment, and ARF. Here, we report a rare manifestation of SSNHL following
      severe postpartum hemorrhage that has simultaneous renal failure and cochlear
      impairment. The patient was a 22-year-old primigravida woman with term pregnancy
      who after delivery and episiotomy hematoma and postpartum hemorrhage subsequently
      suffered from kidney failure, oliguria, and SSNHL that occurred after 3 days of
      delivery. In conditions such as severe postpartum bleeding leading to acute renal
      involvement, the possibility of simultaneous involvement of cochlea due to
      hypoxia or received drugs should be considered.

PMID- 28761209
TI  - Extranodal Non-Hodgkin's Lymphoma of the Oral Cavity: A Case Report.
AB  - Lymphomas are solid malignant tumors having a wide spectrum of clinical and
      pathological features. Non-Hodgkin's lymphoma (NHL) is a subtype of lymphoma with
      two-thirds of the cases presenting as lymph node enlargement. The remaining one
      third of NHL cases has been reported in the extranodal sites, including the
      gastro intestinal tract, Waldeyer's ring, bone, skin, and brain. Intraoral non
      Hodgkin's lymphoma is uncommon and may affect either the jaw bones or occur
      within the soft tissues of the oral cavity. Here we report a case of non
      Hodgkin's lymphoma in a 65-year-old male patient who presented with a growth from
      the extraction socket. Non-Hodgkin's lymphoma presenting as a growth from the
      extraction socket is unusual. An orthopantamograph (OPG) was taken which revealed
      a diffuse radiolucent defect in relation to the extraction socket of the left
      lower molar region. Routine hemogram, urine analysis, and chest radiograph were
      normal. Incisional biopsy was performed and the tissue was subjected to
      histopathological examination. Histopathological and immunohistochemical analysis
      confirmed the diagnosis of B-cell lymphoma. The patient was referred to a
      regional cancer institute for further management, where chemotherapy was planned.
      However, prior to chemotherapy, the patient was diagnosed with brain metastasis
      and he expired in hospital within one month.

PMID- 28761210
TI  - Bilateral Hyperplasia of Bartholin's Gland: A Case Report.
AB  - A 37-year-old woman underwent surgery to remove bilateral vulvar masses. The
      masses were firm, non-tender, and immobile. Pathologic finding was a well
      delineated creamy grayish mass with a homogenous grayish solid surface and mild
      edema, chronic inflammatory infiltration, and focal dilation of the ducts with
      squamous metaplasia. The diagnosis was hyperplastic and hypertrophied Bartholin's
      gland. Hyperplasia is a rare etiology for an enlarged Bartholin's gland. Clinical
      presentation of Bartholin's gland nodular hyperplasia is rather specific,
      although inflammatory lesion is the most common cause of swelling of the
      Bartholin's gland in all age groups. Bartholin's hyperplasia should be considered
      in cases with a solid mass. Total surgical excision is required for diagnosis.
      Only a few cases of Bartholin's gland hyperplasia have been reported in the
      literature. Our patient has been receiving regular follow-up examination and
      there is no evidence of dyspareunia, perineal pain, and recurrent disease 12
      months after surgery.

PMID- 28761211
TI  - Holt-Oram Syndrome: A Rare Variant.
AB  - Holt-Oram syndrome is an autosomal dominant disorder, characterised by skeletal
      abnormalities of the upper limb associated with congenital heart defect, mainly
      atrial and ventricular septal defects. Skeletal defects exclusively affect the
      upper limbs in the preaxial radial ray distribution and are bilateral and
      asymmetrical. They range from clinodactyly, absent or digitalised thumb,
      hypoplastic or absent radii, and first metacarpal to hypoplastic ulna and carpal
      bone anomalies. Cardiac involvement ranges from asymptomatic conduction
      disturbances to multiple structural defects. Structural defects are seen in 75%
      of the cases and include both atrial and ventricular septal defect. More complex
      cardiac lesions such as Tetrology of Fallot, endocardial cushion defects, double
      outlet right ventricle, and total anomalous pulmonary venous return are observed
      uncommonly. An aneurysm of the interatrium septum is an infrequent finding in
      infants. It has been speculated that atrial septal aneurysm (ASA) is a direct
      source of thrombus formation. Paradoxical embolism of venous thrombi across a
      right to left shunt is possibly responsible for the cryptogenic stroke in a
      patient with ASA. However, coagulopathy associated with cyanotic congenital heart
      defect may also be contributory. Our patient had a rare association of complex
      cardiac lesion (tricuspid atresia, pulmonary stenosis, atrial septal aneurysm)
      with cardiac conductive defects and left parietal infarct along with the usual
      skeletal abnormalities.

PMID- 28761212
TI  - Adherence to Hypoglycemic Medication among Insulin-Treated Patients with Type 2
      Diabetes.

PMID- 28761213
TI  - I Am Not a Diabetic.

PMID- 28761214
TI  - Diabetes and Back Pain: Markers of Diabetes Disease Progression Are Associated
      With Chronic Back Pain.
AB  - IN BRIEF Diabetes has been associated with the incidence of back pain. However,
      the relationship between markers of diabetes progression and back pain has not
      been studied. The objective of this study was to correlate clinical and
      laboratory measures of diabetes disease severity to the presence of back pain to
      provide insight into the relationship between these conditions. Findings showed
      that markers of diabetes disease progression were associated with the presence of
      back pain, suggesting that uncontrolled diabetes may contribute to the
      development of chronic back pain.

PMID- 28761215
TI  - Comparison of A1C to Oral Glucose Tolerance Test for the Diagnosis of Prediabetes
      in Overweight and Obese Youth.
AB  - IN BRIEF This study reports performance of A1C against the oral glucose tolerance
      test (OGTT) in predicting prediabetes among overweight and obese African-American
      and Caribbean children. A retrospective chart review was completed for 230
      children. Receiver operating characteristic curves were generated to find the
      predictive performances of different tests against the OGTT. A1C alone is a poor
      discriminator of prediabetes in our study population, with low sensitivity (70%)
      and specificity (48.8%). BMI z score, A1C, and homeostatic model assessment of
      insulin resistance are significant predictors of prediabetes and, when taken
      together, provide better discrimination for prediabetes.

PMID- 28761216
TI  - Use of Canagliflozin in Combination With and Compared to Incretin-Based Therapies
      in Type 2 Diabetes.
AB  - In Brief Sodium-glucose cotransporter 2 (SGLT2) inhibitors and incretin-based
      therapies (dipeptidyl peptidase-4 [DPP-4] inhibitors and glucagon-like peptide-1
      [GLP-1] receptor agonists) are widely used to treat patients with type 2
      diabetes. In clinical and real-world studies, canagliflozin, an SGLT2 inhibitor,
      has demonstrated superior A1C lowering compared to the DPP-4 inhibitor
      sitagliptin. Canagliflozin can also promote modest weight/fat loss and blood
      pressure reduction. The addition of canagliflozin to treatment regimens that
      include a DPP-4 inhibitor or a GLP-1 receptor agonist has been shown to further
      improve glycemic control, while still maintaining beneficial effects on
      cardiometabolic parameters such as body weight and blood pressure. Overall, the
      available clinical and real-world evidence suggests that canagliflozin is a safe
      and well-tolerated treatment option that can be considered either in addition to
      or instead of incretin-based therapies for patients with type 2 diabetes.

PMID- 28761218
TI  - Development and Implementation of a U-500 Regular Insulin Program in a Federally
      Qualified Health Center.

PMID- 28761217
TI  - Metformin Use in Practice: Compliance With Guidelines for Patients With Diabetes
      and Preserved Renal Function.
AB  - IN BRIEF Several contraindications limit the use of metformin, most notably the
      risk of lactic acidosis. This article reports on an examination of a population
      of patients with diabetes with preserved renal function to evaluate provider
      compliance with guidelines on metformin use and to identify factors that
      contributed when practice diverged from recommendations. It found that metformin
      was withheld from approximately one-third of these patients because of 1) an
      existent contraindication to metformin, 2) patient behavior or preference, or 3)
      provider preference or bias based on patient or personal factors. Although
      providers generally follow current recommendations for the use of metformin,
      deviations from guidelines in practice are common.

PMID- 28761219
TI  - Hypertension Control in the University of Chicago Primary Care Group.
AB  - In Brief "Quality Improvement Success Stories" are published by the American
      Diabetes Association in collaboration with the American College of Physicians,
      Inc., and the National Diabetes Education Program. This series is intended to
      highlight best practices and strategies from programs and clinics that have
      successfully improved the quality of care for people with diabetes or related
      conditions. Each article in the series is reviewed and follows a standard format
      developed by the editors of Clinical Diabetes. The following article describes a
      successful project by faculty at the University of Chicago to improve blood
      pressure control among hypertensive patients at a general internal medicine
      clinic on the South Side of Chicago, Ill.

PMID- 28761221
TI  - GOOD TO KNOW: All About Your Risk for Prediabetes, Type 2 Diabetes, and Heart
      Disease.

PMID- 28761220
TI  - Ways Health Care Providers Can Promote Better Medication Adherence.

PMID- 28761222
TI  - Basaglar.

PMID- 28761223
TI  - Left Lower Arm Hemichorea: An Unusual Presentation of New-Onset Type 2 Diabetes.

PMID- 28761224
TI  - Mucormycosis and Cytomegalovirus Co-infection in Renal Transplant Recipients.

PMID- 28761225
TI  - Choking the Feeder.

PMID- 28761226
TI  - Proton Pump Inhibitors: More Indigestion than Relief?
AB  - Proton pump inhibitors (PPIs) are widely prescribed to treat a number of
      gastrointestinal (GI) disorders due to excessive acid production. While effective
      and safe, adverse renal effects have been increasingly described in
      epidemiological literature. The most well-documented adverse renal outcome is
      acute interstitial nephritis; however, association with overall acute kidney
      injury has also been recently reported. Recently, two observational studies have
      linked PPI use with chronic kidney disease. Finally, hypomagnesemia is another
      reported complication and is thought to be resulting from GI loss of magnesium.
      This study will critically review literature on the effect of PPIs on the kidney.

PMID- 28761227
TI  - Acute Kidney Injury in Pregnancy-specific Disorders.
AB  - The incidence of acute kidney injury in pregnancy (P-AKI) has declined
      significantly over the last three decades in developing countries. However, it is
      still associated with significant fetomaternal mortality and morbidity. The
      diagnosis of P-AKI is based on the serum creatinine increase. The usual formulas
      for estimating glomerular filtration rate (GFR) are not validated in this
      population. The incidence of P-AKI with respect to total AKI cases has decreased
      in the last three decades from 25% in 1980s to 9% in 2000s at our centre. During
      the first trimester of gestation, AKI develops most often due to septic abortion
      or hyperemesis gravidarum. Septic abortion related AKI with respect to total AKI
      decreased from 9% to 5% in our study. Prevention of unwanted pregnancy and
      avoidance of septic abortion are keys to eliminate abortion associated AKI in
      early pregnancy. However, we have not seen AKI on account of hyperemesis
      gravidarum over a period of 33 years at our center. In the third trimester, the
      differential diagnosis of AKI in association with pregnancy specific conditions
      namely preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic
      microangiopathies of pregnancy (P-TMA) is more challenging, because these 3
      conditions share several clinical features of thrombotic microangiopathy which
      makes the diagnosis very difficult on clinical grounds. It is imperative to
      distinguish these conditions to make appropriate therapeutic decisions.
      Typically, AFLP and HELLP syndrome improve after delivery of the fetus, whereas
      plasma exchange is the first-line treatment for pregnancy associated thrombotic
      microangioathies (P-TMA). We observed that preclampsia/eclampsia is the most
      common cause of AKI in late third trimester and postpartum periods followed by
      puerperal sepsis and postpartum hemorrhage. Pregnancy-associated thrombotic
      microangiopathies (aHUS/TTP) and AFLP are rare causes of AKI during pregnancy in
      developing countries.

PMID- 28761229
TI  - Impact of Malnutrition, Inflammation, and Atherosclerosis on the Outcome in
      Hemodialysis Patients.
AB  - Malnutrition, inflammation, and atherosclerosis are significant problems in
      patients on hemodialysis. A prospective, observational study in 100 hemodialysis
      patients for 2 years was conducted. The primary outcomes were hospitalizations
      and mortality at the end of 2 years. The mean age was 61 +/- 11.3 years and 69%
      were male. Seven patients did not complete the study (five underwent transplant
      and two were shifted to other units). Serum albumin was significantly lower in
      malnourished patients at 6 months from the beginning of the study period (3.58
      vs. 3.79 g/dl, P = 0.001). Malnutrition based on subjective global assessment
      (SGA) was seen in 30 (32%) patients: mild to moderate in 27 (29%) and severe in 3
      (3%). Inflammation was seen in 73 (78.5%) patients and intimal-medial thickness
      of >1.1 mm indicating significant atherosclerosis was seen in 73 (78.5%)
      patients. Modified SGA score and malnutrition-inflammation score (MIS) were
      significantly more in the malnourished group. Statistically significant
      association was seen between hospitalization and mortality in the malnourished
      population, and the odds ratio of death in malnourished patients was 9.83 (95%
      confidence interval: 2.8-34.3, P < 0.001). There was a moderate correlation
      between malnutrition assessed by modified SGA and MIS score (r = 0.54, P <
      0.001). Mortality rate was 37% in patients with mild to moderate and 67% in
      severe malnutrition. Hospital admission was seen in 43 (46%) patients and was
      significantly more common in malnourished compared to well-nourished patients
      (77% vs. 32%, P < 0.001). Multiple logistic regression analysis showed that
      malnutrition by Modified SGA was the only significant variable associated with
      mortality at 2 years, and addition of MIS score did not improve the predictive
      ability of the model to modified SGA. We recommend the use of modified SGA and
      serial serum albumin to monitor nutrition in hemodialysis patients.

PMID- 28761228
TI  - Kidney Disease in Human Immunodeficiency Virus-seropositive Patients: Absence of
      Human Immunodeficiency Virus-associated Nephropathy was a Characteristic Feature.
AB  - Human immunodeficiency virus (HIV) infection can cause a broad spectrum of renal
      diseases. However, there is paucity of Indian data on the patterns of renal
      lesions in HIV-seropositive patients. The aim of the present study was to
      delineate the spectrum of renal lesions in HIV/acquired immunodeficiency syndrome
      patients. In this prospective study, all HIV-positive patients of both genders
      aged >18 years were screened for renal disease. Patients with proteinuria of more
      than 1 g/24 h were subjected to renal biopsy. A total of 293 HIV-positive
      patients were screened; of these, 136 (46.4%) patients found to have renal
      involvement. Dipstick-positive proteinuria of 1+ or more was observed in 112
      (38.2%) patients, and 16 (14.2%) patients had proteinuria of more than 1 g/24 h.
      Renal biopsy in 14 cases revealed glomerulonephritis (GN) in 12 (85.7%) (isolated
      GN in 4 [28.5%] and GN mixed with chronic TIN in 8 [57.1%]) patients. These
      include mesangioproliferative GN in 5 (35.7%), membranoproliferative GN in 2
      (14.2%), focal segmental glomerulosclerosis in 2 (14.2%), diffuse proliferative
      GN in 2 (14.2%), and diabetic nephropathy in 1 (7.1%) patients. Chronic
      interstitial nephritis was noted in 10 (71.42%) (superimposed on GN in 8 [57.1%],
      isolated in 2 [14.2%]) patients. Granulomatous interstitial nephritis was seen in
      3 (24.1%) cases. GN and chronic interstitial nephritis were noted in 85.7% and
      71.42% of patients, respectively, mostly superimposed on each other.
      Mesangioproliferative GN was the most common glomerular lesion, but classical HIV
      associated nephropathy was not observed.

PMID- 28761230
TI  - Renal Biopsy in Paroxysmal Nocturnal Hemoglobinuria: An Insight into the Spectrum
      of Morphologic Changes.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, potentially life
      threatening disease of blood, characterized by complement-induced intravascular
      hemolytic anemia and thrombosis. PNH can sometimes present directly with renal
      manifestations, without showing any hematological manifestation. It, therefore,
      becomes essential for clinicians and pathologists to be aware of the spectrum of
      renal changes in PNH. The aim of this study was to document the morphologic
      changes observed in renal biopsies in patients with PNH. This is an observational
      study. We report three cases that presented with acute or chronic renal
      insufficiency and were suspected as PNH on viewing their renal biopsy in light of
      their clinical and laboratory details. All the three cases were confirmed as PNH
      on the basis of flow cytometric analysis of CD55 and CD59. Renal biopsy in these
      patients showed a variety of morphologic changes, however the most consistent
      finding was moderate-to-heavy siderosis in their kidneys. PNH per se may be
      difficult to diagnose clinically and sometimes present directly with renal
      manifestations. It is, therefore, prudent for nephrologists and
      nephropathologists to be aware of the spectrum of renal changes in PNH.

PMID- 28761231
TI  - Renal Manifestations in Paroxysmal Nocturnal Hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired chronic disorder
      characterized by a triad of clinical features - hemolytic anemia, pancytopenia,
      and thrombosis. Not many reports of renal involvement in PNH are available in
      literature. We present a case series of PNH with renal involvement. We present
      the data of PNH patients who attended to Departments of General Medicine and
      Nephrology at a government-run tertiary care institute in South India. The
      diagnosis of PNH in these patients during initial phase, between 1998 and 2004
      was based on sucrose lysis and Ham's test. After 2004, the diagnosis was based on
      flow cytometry to detect CD59 (membrane inhibitor of reactive lysis), a
      glycoprotein, and CD55 (decay accelerating factor) in regulation of complement
      action. The patient data were collected from 1998 to 2014. There were 14 patients
      of PNH in this period. The mean age was 37 years and the range was 16-68 years.
      There were eight females. Acute kidney injury (AKI) was noted in six patients.
      Dialysis was performed in four of them. The mean serum creatinine and urea at the
      initiation of dialysis were 5.4 +/- 0.6 and 64.1 +/- 6.1 mg/dl, respectively. The
      median number of hemodialysis sessions done was four. Renal biopsy was done in
      four patients. In three patients, the urinalysis and serum chemistry were
      suggestive of Fanconi syndrome. In our patients, three renal manifestations of
      PNH were identified. They were AKI, renal vessel thrombosis, and Fanconi
      syndrome. Chronic renal failure was not identified.

PMID- 28761232
TI  - Medication Adherence in Kidney Transplant Recipients in an Urban Indian Setting.
AB  - Medication nonadherence is a known problem after renal transplantation and can
      vary from one setting to another. Since it can lead to negative outcomes, it is
      important to develop intervention strategies to enhance adherence in a given
      setting using determinants identified through exploratory studies. We explored
      nonadherence in renal transplant recipients. A longitudinal survey was done with
      adult renal transplant recipients at a tertiary care public and two private
      hospitals of Kolkata. Subjects were followed-up for 1 year. After screening for
      medication adherence status by the four-item Morisky Medication Adherence Scale,
      those admitting to potential nonadherence were probed further. A patient was
      deemed to be nonadherent if failing to take medicines on appointed time (doses
      missed or delayed by more than 2 h) more than three times in any month during the
      observation period. A pretested questionnaire was used to explore potential
      determinants of nonadherence. Data of 153 patients recruited over a 2-year were
      analyzed. The extent of nonadherence with immunosuppressant regimens was about
      31% overall; 44% in the public sector and 19% in the private sector (P < 0.001).
      Nonadherence with other medication was around 19% in both the sectors. Several
      potential demographic, socioeconomic and psychosocial determinants of
      nonadherence were identified on univariate analysis. However, logistic regression
      analysis singled out only the economic status. This study had updated the issue
      of nonadherence in renal transplant recipients in the Indian setting. Strategies
      to improve medication adherence can be planned by relevant stakeholders on the
      basis of these findings.

PMID- 28761233
TI  - Measured Glomerular Filtration Rate at Dialysis Initiation and Clinical Outcomes
      of Indian Peritoneal Dialysis Patients.
AB  - The optimal time for dialysis initiation remains controversial. Studies have
      failed to show better outcomes with early initiation of hemodialysis; even a few
      had shown increased adverse outcomes including poorer survival. Few studies have
      examined the same in patients on peritoneal dialysis (PD). Measured glomerular
      filtration rate (mGFR) not creatinine-based estimated GFR is recommended as the
      measure of kidney function in end-stage renal disease (ESRD) patients. The
      objective of this observational study was to compare the outcomes of Indian
      patients initiated on PD with different residual renal function (RRF) as measured
      by 24-h urinary clearance method. A total of 352 incident patients starting on
      chronic ambulatory PD as the first modality of renal replacement therapy were
      followed prospectively. Patients were categorized into three groups as per mGFR
      at the initiation of PD (<=5, >5-10, and >10 ml/min/1.73 m2). Patient survival
      and technique survival were compared among the three groups. Patients with GFR of
      <=5 ml/min/1.73 m2 (hazard ratio [HR] - 3.42, 95% confidence interval [CI] - 1.85
      6.30, P = 0.000) and >5-10 ml/min/1.73 m2 (HR - 2.16, 95% CI - 1.26-3.71, P =
      0.005) had higher risk of mortality as compared to those with GFR of >10
      ml/min/1.73 m2. Each increment of 1 ml/min/1.73 m2 in baseline GFR was associated
      with 10% reduced risk of death (HR - 0.90, 95% CI - 0.85-0.96, P = 0.002).
      Technique survival was poor in those with an initial mGFR of <=5 ml/min/1.73 m2
      as compared to other categories. RRF at the initiation was also an important
      factor predicting nutritional status at 1 year of follow-up. To conclude,
      initiation of PD at a lower baseline mGFR is associated with poorer patient and
      technique survival in Indian ESRD patients.

PMID- 28761234
TI  - The Epidemiology, Clinical Features, and Outcome of Infection-related
      Glomerulonephritis from East India: A Single Center Experience.
AB  - Infection-related glomerulonephritis (IRGN) is an example of immunological renal
      injury due to non-renal infections. With the changing face of IRGN over the
      years, renal biopsy definitely has an important role to play in differentiating
      this disease from the other masquerades and helps in prognosticating the long
      term outcomes. This prospective study includes biopsy-proven IRGN cases who
      presented to us from July 2010 to July 2013 from a single center in East India.
      Of the 168 patients suspected and screened, 137 patients were proved to have
      IRGN. About 11.67% cases were proven to be immunoglobulin A-IRGN variant. The
      mean age of presentation was 22.7 +/- 15.8 years with a slight male
      preponderance. A nephrotic range of proteinuria was seen in 13.8% cases and 17.5%
      patient required renal replacement therapy at presentation. Around 8.75% patients
      had persistent proteinuria despite normal renal function beyond 6 months of
      follow-up and 8.09% patients progressed to chronic kidney disease. It may no
      longer be classified as a glomerular disease with the definite favorable outcome
      as an important number of patients may progress to chronicity following this
      disease. Renal biopsy plays an important role in the assessment of prognosis of
      IRGN and detection of the presence of other underlying glomerulonephritis and
      should be considered early, especially in patients with atypical presentation.

PMID- 28761235
TI  - Renal Artery Thrombosis with Renal Infarction: A Rare Cause of Acute Abdomen.
AB  - Renal artery thrombosis with renal infarction is a rare entity. Due to the
      nonspecific clinical presentation, the diagnosis is usually delayed. We describe
      such a case in a middle-aged man with membranous nephropathy who was in remission
      and presented with severe abdominal pain. He was managed with selective intra
      arterial thrombolysis with a good outcome.

PMID- 28761236
TI  - Primary Renal Echinococcosis.
AB  - Echinococcosis is a parasitic infection caused by the larval stage of a cestode
      Echinococcus granulosus and is endemic in sheep farming regions of developing
      countries. It manifests as hydatid cyst and most commonly is found in liver
      followed by lungs. Renal hydatid cyst is rare and amounts for 2% of all cases.
      There are no specific clinical manifestations, and hence diagnosis of renal
      hydatid disease is missed out easily without imaging. We report a case of 50-year
      old female who had 6 months history of lower abdominal pain with hematuria, found
      to have right renal hydatid cyst on imaging which was treated with right
      nephrectomy with pre- and post-operative albendazole treatment.

PMID- 28761237
TI  - Membranoproliferative Glomerulonephritis Associated with a Human Immunodeficiency
      Virus Infection.
AB  - Type 1 membranoproliferative glomerulonephritis (MPGN) is an uncommon
      manifestation of human immunodeficiency virus (HIV)-associated renal disease in
      patients coinfected with hepatitis C virus. We report a case of MPGN
      characterized by nephrotic syndrome associated with HIV without hepatitis C
      coinfection. The patient had a favorable response to highly active antiretroviral
      therapy and angiotensin-converting enzyme inhibitors. Recognition of the MPGN
      lesion in HIV infection devoid of hepatitis C coinfection must be considered.

PMID- 28761238
TI  - Dengue Fever-induced Thrombotic Microangiopathy: An Unusual Cause of Renal
      Failure.
AB  - Dengue fever is a tropical infection, which is mosquito-borne disease, caused by
      dengue virus and spread by Aedes mosquitoes. The incidence of dengue fever has
      risen rapidly over the past few years. About half of dengue infections are
      asymptomatic, and a great majority present with fever and body ache. However, the
      occurrence of complications is well known, including acute kidney injury (AKI).
      AKI in dengue is usually attributable to a pre-renal cause. Thrombotic
      microangiopathy is an extremely rare complication of dengue fever, with only a
      few published case reports in medical literature. This case intends to highlight
      the importance of recognizing dengue fever-induced thrombotic microangiopathy by
      physicians and pathologists, enabling better diagnosis and management of this
      life-threatening condition.

PMID- 28761239
TI  - Sequential, Autologous Hematopoietic Stem Cell Transplant Followed by Renal
      Transplant in Multiple Myeloma.
AB  - A 30-year-old female was symptomatic with headache, fatigue, and weakness since
      October 2011 and was told to have anemia. In January 2012, she was admitted
      outside with pulmonary edema. Investigations revealed advanced azotemia, anemia,
      and hypercalcemia. Urine showed 2 + proteins and 30-35 red blood cells. There was
      no history of oral ulcers, rash, Raynaud's phenomenon, or hemoptysis. She was
      evaluated for causes of rapidly progressive "renal failure." Hemolytic work-up;
      antinuclear antibody, double-stranded DNA, and anti-neutrophil cytoplasmic
      antibody were negative. Kidney biopsy was done and interpreted as acute
      interstitial nephritis with hyaline casts. She was started on hemodialysis and
      treated with steroids and cyclophosphamide. She came to our institute in January
      2012. Investigations showed evidence of paraproteinemia with kappa restriction.
      Bone marrow showed 15% plasma cells. Kidney biopsy was reviewed and was
      diagnostic of cast nephropathy. She was treated with 6 monthly cycles of
      dexamethasone and bortezomib. She achieved complete remission in July 2012.
      Maintenance doses of bortezomib were continued until May 2014. Autologous bone
      marrow transplantation was performed on June 06, 2014. Monthly, bortezomib was
      continued till April 2015. Subsequently, workup for renal transplantation was
      started with her father as her donor. Test for sensitization was negative. Renal
      transplantation was done on January 1, 2016, with prednisolone, mycophenolate,
      and tacrolimus. She achieved a serum creatinine of 0.6 mg% on the 4th
      postoperative day. Thereafter, she continues to remain stable.

PMID- 28761240
TI  - Circulating Monoclonal IgG1-kappa Antibodies Causing Anti-glomerular Basement
      Membrane Nephritis.
AB  - Anti-glomerular basement membrane (GBM) antibody disease is a rare but well
      characterized cause of glomerulonephritis. Patients present with rapidly
      progressive renal failure with hemoptysis. Early diagnosis is crucial in
      salvaging the renal damage and life-threatening pulmonary hemorrhage.
      Plasmapheresis and immunosuppression is the mode of therapy. Anti-GBM antibodies
      are polyclonal in nature. However, rare monoclonal antibodies can cause similar
      destruction of glomerular capillary walls. We describe distinct combination of
      circulating monoclonal and anti-GBM nephritis.

PMID- 28761241
TI  - Renal Tubular Acidosis, Osteopetrosis, and Cerebral Calcification: A Rare
      Syndrome Caused by Carbonic Anhydrase II Deficiency.

PMID- 28761242
TI  - Collagenofibrotic Glomerulopathy.

PMID- 28761243
TI  - Editorial Message.

PMID- 28761244
TI  - Substantivity of hypochlorous acid-based disinfectant against biofilm formation
      in the dental unit waterlines.
AB  - OBJECTIVE: The purpose of the study was to examine the substantivity of a new
      disinfectant against biofilm formation in the dental unit waterlines. MATERIALS
      AND METHODS: Twenty dental units were selected for the study and divided into two
      groups: Group A (dental unit waterlines treated with the disinfectant) and Group
      B (untreated dental unit waterlines). Biofilm formation was monitored in both
      groups by removing the one dental unit waterline from each group for the period
      of 10 days. One inch of the dental unit waterline tube was cut at random site,
      and the inner lumen of the cut sections was analyzed using the scanning electron
      microscope (SEM) (TESCAN VEGA3 SBU). RESULTS: On examination, SEM images showed
      that there was no slime layer or bacterial cells seen in cut section for the
      period of 7 days in the treated dental waterlines, which means that there is no
      evident of biofilm formation. In the untreated dental unit waterline cut section,
      slime layer was observed from day 1. CONCLUSION: Disinfectant solution was proved
      to be effective for 7 days against biofilm formation. This technique could be
      used as a valid method for disinfection of dental unit waterlines.

PMID- 28761245
TI  - Comparison of efficiency of ethylenediaminetetraacetic acid, citric acid, and
      etidronate in the removal of calcium hydroxide intracanal medicament using
      scanning electron microscopic analysis: An in-vitro study.
AB  - CONTEXT: Being integral to root canal therapy, obturation can be performed
      adequately only after the removal of intracanal medicament. One technique
      involves the use of chelating agents such as ethylenediaminetetraacetic acid
      (EDTA) and citric acid. Etidronic acid, a relatively new chelator, has smear
      layer removal ability and lesser dentinal erosion. It is untested in calcium
      hydroxide (Ca[OH]2) medicament removal. AIM: The aim of this study was to compare
      the efficiency of irrigation protocols (EDTA, citric acid, and etidronate) in
      Ca(OH)2 removal. MATERIALS AND METHODS: Forty-five single-rooted mandibular
      premolars were decoronated, instrumented, and filled with Ca(OH)2. After 7 days
      incubation, Ca(OH)2 was removed by three irrigation protocols (Group-I: 17% EDTA;
      Group-II: 10% citric acid; and Group-III: 18% etidronate). Roots were split and
      analyzed (scanning electron microscope, *1500). Chelator solution pH was tested.
      Data were analyzed by Kruskal-Wallis ANOVA and Mann-Whitney U-test. RESULTS:
      Group-III (coronal-third) and Groups-I and II (middle-third) had highest
      cleanliness scores; Groups-II and III (apical-third) had lowest scores. Comparing
      the thirds, all groups showed difference in scores. pH of Groups-I, II, and III
      were 6.8, 1.4, and 0.3, respectively. CONCLUSION: The solution pH of citric acid
      and etidronate impacts their Ca(OH)2 removal efficiency in different ways: the
      highly alkaline pH of Ca(OH)2 increases citric acid pH toward neutrality, where
      it becomes an inefficient chelator; on the contrary, high acidity of etidronate
      compensates for its weaker chelation. Etidronate may not require 5 min duration
      for Ca(OH)2 removal due to the likelihood of dentinal erosion.

PMID- 28761247
TI  - Comparison of radiopacity of different composite resins.
AB  - BACKGROUND: The radiopacity of composite resins has been considered as an
      important requirement, improving the radiographic diagnosis. AIM: The present
      study aimed to compare the radiopacity of eight different composite materials
      using an aluminum step wedge. MATERIALS AND METHODS: Eight different composite
      resins were used in this study. The samples were prepared using a stainless steel
      mold (2 * 8), and a 2-mm-thickness horizontal section was obtained from the
      freshly extracted molar tooth. Three different radiographs were taken by
      establishing standard conditions. Mean gray values were obtained by taking three
      measurements from each step of both the tooth and the aluminum step wedge, and
      the aluminum thickness equivalents were calculated. Statistical analysis was
      performed using one-way variance analysis and Tukey's test (P < 0.05). RESULTS:
      All aluminum thickness equivalents were found to be higher than those of the
      enamel and dentin, except Clearfil Majesty Esthetic (2.23 mm +/- 0.52 mm) and
      Filtek Silorane (3.67 mm +/- 0.15 mm) (P < 0.05). The Clearfil Majesty Posterior
      (8.50 mm +/- 0.10 mm) and Arabesk Top (8.17 mm +/- 0.06 mm) were found to be the
      most radiopaque composites. CONCLUSION: All composite resin materials tested in
      this study were confirmed to the International Standards Organization 4049
      standards. However, since radiopacity is not the only criterion for clinical use,
      it is a better approach to take all other properties of the materials into
      consideration.

PMID- 28761246
TI  - Efficacy of two rotary retreatment systems in removing Gutta-percha and sealer
      during endodontic retreatment with or without solvent: A comparative in vitro
      study.
AB  - OBJECTIVES: The aim of this in vitro study was to compare the efficacy of two
      retreatment rotary systems in the removal of Gutta-percha (GP) and sealer from
      the root canal walls with or without solvent. MATERIALS AND METHODS: Forty-eight
      extracted human mandibular first premolars were prepared and obturated with GP
      and AH Plus sealer. Samples were then randomly divided into four groups. Group I
      was retreated with MtwoR rotary system without solvent, Group II was retreated
      with MtwoR rotary system with Endosolv R as the solvent, Group III with D-RaCe
      rotary system without solvent, and Group IV with D-RaCe rotary system and
      Endosolv R solvent. The cleanliness of canal walls was determined by
      stereomicroscope (*20) and AutoCAD software. Kruskal-Wallis test and Mann-Whitney
      U-test were used to compare the data. RESULTS: Results showed that none of the
      retreatment systems used in this study was able to completely remove the root
      canal filling material. D-RaCe with or without solvent showed significantly (P >
      0.05) less filling material at all levels compared to MtwoR with/without solvent.
      CONCLUSION: Within the limitation of the current study, D-RaCe rotary retreatment
      system is more effective in removing filling material from root canal walls when
      compared to MtwoR rotary retreatment system.

PMID- 28761248
TI  - A comparative evaluation of the effect of 8% and 17% ethylenediaminetetraacetic
      acid exposure for 1 min and 10 min on the fracture resistance of endodontically
      treated roots: An in vitro study.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of 8% and 17%
      ethylenediaminetetraacetic acid (EDTA) exposure for 1 min and 10 min on the
      fracture resistance of endodontically treated roots. METHODOLOGY: Sixty human
      single-rooted teeth were decoronated and divided into six groups (n = 10). Canal
      preparation was carried out except in negative control group, using the ProTaper
      rotary file system. Final irrigation was performed using distilled water, 17%
      EDTA for 1 min and 10 min, 8% EDTA for 1 min and 10 min. Thereafter, roots were
      obturated with ProTaper F3 Gutta-percha points and AH Plus sealer using a single
      cone technique. The specimens were loaded vertically at 1 mm/min crosshead speed
      until vertical root fracture occurred. Results were evaluated statistically with
      one-way analysis of variance and post hoc Tukey test. RESULTS: Analysis of
      results showed that the unprepared roots showed the highest fracture resistance
      and roots irrigated with 17% EDTA for 10 min showed the lowest fracture
      resistance. The mean fracture resistance of unprepared roots, roots irrigated
      with 8% EDTA for 10 min and 17% EDTA for 1 min was significantly higher than
      roots irrigated with 8% EDTA for 1 min, 17% EDTA for 10 min and distilled water.
      CONCLUSION: From a clinical viewpoint, if EDTA has to be used, it is safer to use
      higher concentration for a shorter application time or a low concentration with a
      longer application time. Prolonged use of high concentrations of EDTA might
      increase the risk of root fracture.

PMID- 28761249
TI  - Retrievability of calcium hydroxide intracanal medicament with three calcium
      chelators, ethylenediaminetetraacetic acid, citric acid, and chitosan from root
      canals: An in vitro cone beam computed tomography volumetric analysis.
AB  - AIM: This study compared the amount of aqueous-based and oil-based calcium
      hydroxide remaining in the canal, after removal with two different chelators 17%
      EDTA, 20% Citric acid and 0.2% Chitosan in combination with ultrasonic agitation.
      METHODS AND MATERIAL: Cleaning and shaping of root canals of 28 mandibular
      premolar was done and canals were filled either with Metapex or Ca(OH)2 mixed
      with distilled water. Volumetric analysis was performed utilizing cone beam
      computed tomography (CBCT) after seven days of incubation. Ca(OH)2 was removed
      using either 17% EDTA, 20% Citric acid or 0.2% Chitosan in combination with
      ultrasonic agitation. STATISTICAL ANALYSIS USED: Volumetric analysis was repeated
      and percentage difference was calculated and statistically analyzed using Kruskal
      Wallis and Mann-Whitney U test. RESULTS: All the three chelators failed to remove
      aqueous-based as well as oil-based Ca(OH)2 completely from the root canal.
      Aqueous-based Ca(OH)2 was easier to be removed than oil-based Ca(OH)2. 0.2%
      Chitosan in combination with ultrasonics performed better than 17% EDTA and 20%
      citric acid in removal of Ca(OH)2. CONCLUSION: Combination of 0.2% Chitosan and
      ultrasonic agitation results in lower amount of Ca(OH)2 remnants than 17% EDTA,
      20% Citric acid irrespective of type of vehicle present in the mix.

PMID- 28761250
TI  - Apical extrusion of debris in four different endodontic instrumentation systems:
      A meta-analysis.
AB  - BACKGROUND: All endodontic instrumentation systems tested so far, promote apical
      extrusion of debris, which is one of the main causes of postoperative pain, flare
      ups, and delayed healing. OBJECTIVES: Of this meta-analysis was to collect and
      analyze in vitro studies quantifying apically extruded debris while using Hand
      ProTaper (manual), ProTaper Universal (rotary), Wave One (reciprocating), and
      self-adjusting file (SAF; vibratory) endodontic instrumentation systems and to
      determine methods which produced lesser extrusion of debris apically.
      METHODOLOGY: An extensive electronic database search was done in PubMed, Scopus,
      Cochrane, LILACS, and Google Scholar from inception until February 2016 using the
      key terms "Apical Debris Extrusion, extruded material, and
      manual/rotary/reciprocating/SAF systems." A systematic search strategy was
      followed to extract 12 potential articles from a total of 1352 articles. The
      overall effect size was calculated from the raw mean difference of weight of
      apically extruded debris. RESULTS: Statistically significant difference was seen
      in the following comparisons: SAF < Wave One, SAF < Rotary ProTaper. CONCLUSIONS:
      Apical extrusion of debris was invariably present in all the instrumentation
      systems analyzed. SAF system seemed to be periapical tissue friendly as it caused
      reduced apical extrusion compared to Rotary ProTaper and Wave One.

PMID- 28761251
TI  - The effect of a dentin desensitizer on the shear bond strength of composite to
      dentin using three different bonding agents: An in vitro study.
AB  - OBJECTIVE: The effect of dentin desensitizer Systemp on the shear bond strength
      of composite resin to dentin using three different bonding agents, i.e., Prime &
      Bond NT, Xeno V+, and Futurabond DC were evaluated. MATERIALS AND METHODS: Sixty
      recently extracted human premolars were divided into six groups of ten teeth
      each. The superficial dentin was etched with 37% phosphoric acid. In Groups I,
      II, and III, Prime & Bond NT, Xeno V+, and Futurabond DC, respectively, were
      applied to dentin and composite placed. Following application of dentin
      desensitizer Systemp in Groups IV, V, and VI, Prime & Bond NT, Xeno V+, and
      Futurabond DC, respectively, were applied to dentin and composite placed. The
      shear bond strength was evaluated. Data obtained were statistically analyzed
      using one-way analysis of variance, post hoc, and Dunnett's test. RESULTS:
      Following application of dentin desensitizer Systemp, mean shear bond strength
      increased when Prime & Bond NT bonding agent was used while it decreased for Xeno
      V+ and Futurabond DC bonding agents. CONCLUSION: Within the limitations of this
      in vitro study, it was observed that following application of dentin desensitizer
      Systemp, mean shear bond strength may increase or decrease depending on the
      bonding agents used.

PMID- 28761252
TI  - Additive effect of photoactivated disinfection on the antibacterial activity of
      QMix 2in1 against 6-week Enterococcus faecalis biofilms: An in vitro study.
AB  - BACKGROUND: Evaluation of the additive effect of photodynamic therapy (PDT) on
      the antibacterial activity of 2.5% sodium hypochlorite (NaOCl) and QMix against 6
      week Enterococcus faecalis biofilms contaminated root canals. AIMS: To establish
      the most suitable irrigant for eradication of 6-week E. faecalis biofilms.
      SETTINGS AND DESIGN: In vitro study. MATERIALS AND METHODS: A 6-week E. faecalis
      (ATCC 29212) biofilm was formed in 190 extracted teeth that were subsequently
      subjected to irrigation protocols as follows. Group A1: normal saline, Group A2:
      2.5% NaOCl, Group A3: QMix, Group B1: normal saline and photoactivated
      disinfection (PAD), Group B2: 2.5% NaOCl and PAD, Group B3: QMix and PAD, Group
      C: no irrigation. For PAD, irradiation was done three times for 5 s each with 10
      s interval on continuous mode with a 980 nm diode laser. Samples from the root
      canals were collected and plated onto brain heart infusion agar plates to
      determine the colony-forming unit/ml. STATISTICAL ANALYSIS USED: One-way ANOVA,
      post hoc Tukey's honest significant difference test. RESULTS: Maximum percentage
      of disinfection (99%) was seen in Group B2 (NaOCl with PDT), which was similar to
      Groups A2 (97.6%) and B3 (98.8%) (P < 0.0001). CONCLUSIONS: NaOCl with PDT gave
      maximum disinfection.

PMID- 28761253
TI  - Determining predictability and accuracy of thermal and electrical dental pulp
      tests: An in vivo study.
AB  - INTRODUCTION: Pulp sensitivity testing, even with its limitations and
      shortcomings, has been and still remains a very helpful aid in endodontic
      diagnosis. Pulp sensitivity tests extrapolate pulpal health from the sensory
      response. The aim of the present study was to identify the sensitivity,
      specificity, positive and negative predictive values (NPVs) of thermal and
      electrical tests of pulp sensitivity. MATERIALS AND METHODS: Pulp tests studied
      were two cold and heat tests respectively and electrical test. A total of 330
      teeth were tested: 198 teeth with vital pulp and 132 teeth with necrotic pulps
      (disease prevalence of 40%). The ideal standard was established by observing
      bleeding within the pulp chamber. RESULTS: Sensitivity values of the diagnostic
      tests were 0.89 and 0.94 for cold test, 0.84 and 0.87 for the heat tests, and
      0.75 for electrical pulp test and the specificity values of the diagnostic tests
      were 0.91 and 0.93 for the cold tests, 0.86 and 0.84 for the heat tests, and 0.90
      for electrical pulp test. The NPVs were 0.91 and 0.96 for the cold tests, 0.89
      and 0.91 for the heat tests, and 0.84 for electrical pulp test. The positive
      predictive values were 0.89 and 0.90 for the cold tests, 0.80 and 0.79 for the
      heat tests and 0.88 for electrical pulp test. The highest accuracy (0.9393) was
      observed with cold test (icy spray). CONCLUSIONS: The cold test done with icy
      spray was the most accurate method for sensitivity testing.

PMID- 28761254
TI  - Mandibular second molar exhibiting a unique "Y-" and "J-" "shaped" root canal
      anatomy diagnosed using cone-beam computed tomographic scanning: A case report.
AB  - This article aims to report a unique case with aberrant root canal anatomy
      exhibiting "Y-" and "J"-shaped canal pattern in a mandibular second molar.
      Anatomic complexities may pose challenges for endodontic treatment. Before
      performing endodontic treatment, the clinician should be aware of the internal
      anatomy of the tooth being treated and should recognize anatomic aberrations if
      present. Presence of unusual anatomy may call for modifications in treatment
      planning. This report describes in detail about a mandibular second molar tooth
      associated with two paramolar tubercles having a peculiar "Y-" and "J-"shaped
      canal anatomy detected with the aid of cone beam computed tomography, which has
      never been reported in the dental literature. The proposed treatment protocol for
      the endodontic management of the same has also been discussed.

PMID- 28761255
TI  - Surgical management of lateral incisor with type II dens invaginatus and a
      periapical pathosis: A case report with 1-year follow-up.
AB  - Dens invaginatus is a relatively common dental malformation resulting from an
      infolding of enamel organ into the dental papilla varying in depth into the tooth
      tissues. Complex morphological anatomy associated with the pulpal pathology
      presents inaccessibility to completely remove the necrotic pulp tissues and hence
      poses challenges in rendering endodontic treatment. A combination of nonsurgical
      and surgical management in treating such cases is advisable depending on the
      presented variations. The present case reports the surgical endodontic treatment
      of an immature maxillary lateral incisor with type II dens invaginatus and
      periapical pathology.

PMID- 28761256
TI  - Root canal treatment of a fused mandibular incisor using cone-beam computed
      tomography as a diagnostic aid.
AB  - Tooth fusion consists of the union of crowns by the enamel and/or dentin. We
      describe a case of a patient who presented with a fistula in the apical portion
      of teeth 32 and 33. Clinically, tooth 32 showed increased crown width in relation
      to other teeth in the same arch. Radiographic examination evidenced fusion of
      tooth 32 with a possible supernumerary tooth. Cone-beam computed tomography was
      used to confirm the radiographic findings and revealed incomplete apex formation
      of the supernumerary tooth. The fused tooth was subjected to root canal
      treatment. Calcium hydroxide was used as intracanal medication, changed for every
      30 days, for 4 months. Subsequently, the mesial canal received an apical plug of
      mineral trioxide aggregate mixed with distilled water. At 2 years of follow-up,
      the tooth showed signs of tissue repair.

PMID- 28761257
TI  - From Hair in India to Hair India.
AB  - In all cultures, human hair and hairdo have been a powerful metaphor. Tracing
      back the importance and significance of human hair to the dawn of civilization on
      the Indian subcontinent, we find that all the Vedic gods are depicted as having
      uncut hair in mythological stories as well as in legendary pictures. The same is
      true of the Hindu avatars, and the epic heroes of the Ramayana, and the
      Mahabharata. Finally, there are a number of hair peculiarities in India pertinent
      to the creed and religious practices of the Hindu, the Jain, and the Sikh. Shiva
      Nataraja is a depiction of the Hindu God Shiva as the cosmic dancer who performs
      his divine dance as creator, preserver, and destroyer of the universe and conveys
      the Indian conception of the never-ending cycle of time. The same principle
      manifests in the hair cycle, in which perpetual cycles of growth, regression, and
      resting underly the growth and shedding of hair. Finally, The Hair Research
      Society of India was founded as a nonprofit organisation dedicated to research
      and education in the science of hair. Notably, the HRSI reached milestones in the
      journey of academic pursuit with the launch of the International Journal of
      Trichology, and with the establishment of the Hair India conference. Ultimately,
      the society aims at saving the public from being taken for a ride by quackery,
      and at creating the awareness that the science of hair represents a subspecialty
      of Dermatology. In analogy again, the dwarf on which the Nataraja dances
      represents the demon of egotism, and thus symbolizes Shiva's, respectively, the
      HRSI's victory over ignorance.

PMID- 28761258
TI  - Modified Ferriman-Gallwey Score in Hirsutism and its Association with Metabolic
      Syndrome.
AB  - BACKGROUND: Hirsutism is the presence of terminal hair in females in males
      pattern. It occurs in 5%-15% of women. Modified Ferriman-Gallwey (mFG) score of
      >= 8 is considered hirsutism, but there are populations with a low mFG score. In
      clinical practice, hirsutism is subjective. Although hirsutism is considered as a
      purely esthetic problem, it is associated with many underlying disorders,
      especially androgen excess disorders. Polycystic ovarian syndrome (PCOS) disease
      is the most common cause of androgen excess in females, and there are reports of
      its association with metabolic syndrome. Metabolic syndrome occurs alone in
      hirsutism. AIMS: To assess mFG score in patients who consider themselves as
      hirsute. To study the association between metabolic syndrome and hirsutism.
      METHODS: Hospital-based cross-sectional study design was adopted. A structured
      questionnaire was used to collect sociodemographic and clinical data. The
      severity of hirsutism was assessed using mFG score and metabolic syndrome was
      diagnosed by the American Heart Association criteria. mFG score was expressed as
      mean and Student's t-test and Chi-square statistic were used as the tests of
      significance. Logistic regression analysis was performed. RESULTS: The mean mFG
      score was 5.5. Metabolic syndrome was present in 44%. About 65.2% of patients
      with score >=8 had metabolic syndrome, whereas only 37.7% of patients with score
      <8 had metabolic syndrome (P = 0.019). Metabolic syndrome (P = 0.018) and PCOS (P
      = 0.003) were the significant variables in logistic regression analysis.
      Triglyceride levels >=150 mg/dl and waist circumference >=88 cm were the
      components of metabolic syndrome that were significantly associated with
      hirsutism (P = 0.006 in both). CONCLUSIONS: To find the ideal cutoff of mFG score
      to define hirsutism in our population, a population study among females in the
      reproductive age group has to be conducted. As there is a definite association of
      hirsutism and metabolic syndrome, and metabolic syndrome can result in
      cardiovascular complications, any women presenting with terminal hair in a male
      pattern should be evaluated for metabolic syndrome irrespective of the mFG score.

PMID- 28761259
TI  - A Comparative Study of Microneedling with Platelet-rich Plasma Plus Topical
      Minoxidil (5%) and Topical Minoxidil (5%) Alone in Androgenetic Alopecia.
AB  - CONTEXT: There are very few studies evaluating efficacy of platelet-rich plasma
      (PRP) in hair restoration and its combination with microneedling. As far as
      ascertained, there is no study to evaluate efficacy of microneedling with PRP
      plus topical minoxidil (5%) versus topical minoxidil (5%) alone in androgenetic
      alopecia (AGA). AIMS: This study aims (1) to compare the efficacy of (a) topical
      minoxidil (5%) alone and (b) topical minoxidil (5%) + microneedling with PRP in
      men between 18 and 50 years with AGA Grade III to V vertex (Norwood-Hamilton
      scale) and (2) to perform objective and subjective evaluation based on clinical
      improvement and photographic evidence. SETTINGS AND DESIGN: The study was
      conducted in the outpatient department of dermatology, venereology, and leprology
      in tertiary care hospital. It was open, prospective study. SUBJECTS AND METHODS:
      Fifty patients with AGA were selected on the basis of inclusion and exclusion
      criteria. These patients were randomly divided into two groups of 25 patients
      each and were given following treatment: (i) Group A: topical minoxidil (5%)
      alone and (ii) Group B: topical minoxidil (5%) + microneedling with platelet-rich
      plasma (PRP). STATISTICAL ANALYSIS USED: Patients were assessed before starting
      the treatment and at the end of 6 months on the basis of (a) Patient's self
      assessment based on standardized seven-point scale compared with baseline (b)
      Physician's assessment based on standardized seven-point scale of hair growth
      compared with baseline. RESULTS: There was a significant improvement (P < 0.05)
      in both patients' assessment and investigator's assessment in Group B as compared
      to Group A at the end of 6 months. CONCLUSIONS: Microneedling with PRP is safe,
      effective, and a promising tool for the management of AGA.

PMID- 28761260
TI  - Prospective Analytical Controlled Study Evaluating Serum Biotin, Vitamin B12, and
      Folic Acid in Patients with Premature Canities.
AB  - BACKGROUND: Premature canities is a common yet unfathomed disorder. The evidence
      for the role of micronutrient deficiency in premature canities is not well
      established. AIM: The present study was undertaken to evaluate the micronutrient
      levels in Indian patients with premature canities as compared to controls.
      MATERIALS AND METHODS: We conducted a case-control study in 52 self-reporting
      patients with premature canities (<20 years age). Micronutrient levels including
      serum Vitamin B12, biotin, and folic acid were assessed and compared among the
      patients and controls. RESULTS: We observed that mean serum Vitamin B12 (198.07
      +/- 88.98 pg/ml in cases vs. 343.07 +/- 143.06 pg/ml in controls, P = 0.000),
      folic acid (6.22 +/- 2.46 ng/ml in cases vs. 8.49 +/- 4.18 ng/ml in controls, P =
      0.01), and biotin (252.71 +/- 18.79 pg/ml in cases vs. 266.47 +/- 30.44 pg/ml in
      controls, P = 0.013) levels were significantly lower in cases as compared to the
      controls. CONCLUSION: In view of the dark hair and many prevailing myths,
      premature canities is a significant problem in Asians with profound psychosocial
      impact. This study unveils the association with Vitamin B12, folic acid, and
      biotin deficiencies. Larger studies are recommended to arrive on a logical
      conclusion.

PMID- 28761262
TI  - Acute Alopecia: Evidence to Thallium Poisoning.
AB  - Thallium is a toxic heavy metal often involved in criminal poisonings and
      occasionally in accidental poisoning. Here, we report a case of acute,
      nonintentional thallium poisoning due to thallium-contaminated alternative
      medicine for its rarity and to create awareness about the combination of rapid,
      diffuse alopecia with neurologic and gastrointestinal symptoms among
      practitioners, professionals, public, and policymakers.

PMID- 28761263
TI  - A Case of Membranous Aplasia Cutis Congenita and Dermoscopic Features.
AB  - Membranous, bullous, or cystic aplasia cutis congenita is a clinical subtype of
      aplasia cutis, covered with a membranous or glistening surface. A male newborn
      presented at birth with two flat lesions on the left parietal scalp, surrounded
      by a rim of terminal hairs. Physical examination revealed two translucent
      papules. On dermoscopy, they showed a reddish background, thin, lineal vessels
      and, remarkably few hair bulbs could be seen because of the translucency of the
      lesion. No skull bone and brain defects were found. The diagnosis of membranous
      aplasia cutis congenita was established. Histologically, it is characterized by
      an atrophic epidermis with loose fibrovascular stroma and edematous dermal
      stroma. Dermoscopy may help to rule out other entities (herpes simplex,
      epidermolysis bullosa, trauma...) since the atrophic epidermis and fibrovascular
      stroma is evidenced by the hair bulbs and its characteristic translucency
      ("translucency's sign").

PMID- 28761261
TI  - Presence of Mast Cells and Mast Cell Degranulation in Scalp Biopsies of Telogen
      Effluvium.
AB  - BACKGROUND: Telogen effluvium (TE) is a type of acquired, diffuse alopecia that
      occurs due to an abnormal shift of scalp hair follicles from anagen to telogen,
      leading to premature shedding of hair. Previous studies have suggested the
      existence of a neuroimmunologic "brain-hair follicle" axis, in which mast cells
      have been implicated as an important link between the nervous system and
      immunologic system. OBJECTIVE: The current study sought to investigate the role
      of mast cell presence and mast cell degranulation in the pathogenesis of TE.
      MATERIALS AND METHODS: Mast cells were counted using Giemsa and tryptase
      immunohistochemical stains in scalp biopsy specimens with the pathologic
      diagnosis of TE (TE, n = 10), alopecia areata (AA, n = 7), and androgenic
      alopecia (ANDRO, n = 9). RESULTS: We found significant (P < 0.001) group-level
      differences between the mean mast cell counts per high-power fields for each type
      of alopecia studied. Tukey post hoc analysis showed the mean mast cell count for
      TE to be significantly larger than AA for both Giemsa (P = 0.002) and tryptase (P
      = 0.006); significantly larger than ANDRO for both Giemsa (P < 0.001) and
      tryptase (P < 0.001); and significantly larger when compared to normal scalp skin
      for both Giemsa (P < 0.001) and tryptase (P < 0.001). No significant difference
      of mean mast cell counts was observed for AA compared to ANDRO for Giemsa (P =
      0.373) or tryptase (P = 0.598) stains. CONCLUSION: Our findings suggest that mast
      cells could play a role in mediating stress-induced hair loss seen in TE.

PMID- 28761264
TI  - A Case Report of Verruca Vulgaris on basis of Alopecia Areata Successfully
      Treated with Diphenylcyclopropenone.
AB  - Alopecia areata is an autoimmune skin disease which is usually characterized by
      patchy hair loss in effected regions. Diagnosis usually based on clinical
      findings and main treatment options include topical, intralesional, systemic
      corticosteroids, and topical immunotherapy. Verruca vulgaris is an infectious
      disease caused by human papillomavirus which is usually characterized by well
      marginated hyperkeratotic papules or plaques. There are several treatment
      modalities such as physical and chemical destruction and topical immunotherapy. A
      23-year-old male patient presented to our outpatient clinic with multifocal
      noncicatrial alopecic plaques on scalp and multiple periungual verrucous papules
      on bilateral hands. High potent corticosteroid cream and minoxidil lotion 5% were
      offered for his scalp lesions, and topical 5-fluorouracil lotion was initiated
      for his verrucous lesions. In the 1st month visit, we detected contamination of
      viral warts on alopecic plaques of his scalp and all the previous therapeutics
      were stopped. We initiated topical diphenylcyclopropenone (DPCP) sensitization
      weekly. After the fourth application of DPCP, we observed that all of
      hyperkeratotic papules disappeared. Diphencyprone treatment was continued, and
      with further applications, hair growth as vellus type was observed. DPCP is
      relatively beneficial treatment option for both diseases although it is not a
      first-line therapy most times. There are case reports and series about this
      treatment for both of these diseases. We want to present this case to by regard
      of the unusual presentation and efficacy of DPCP in both indications.

PMID- 28761265
TI  - Light Microscopy and Polarized Microscopy: A Dermatological Tool to Diagnose Gray
      Hair Syndromes.
AB  - Gray hair syndromes are rare syndromes which have an autosomal recessive
      inheritance and are characterized by pigmentary dilution of skin and hair,
      defects in immunological function, and nervous system defects. They comprise
      three disorders namely Chediak-Higashi syndrome (CHS), Griscelli syndrome (GPS),
      and Elejalde syndrome. Clinically, it is difficult to distinguish these disorders
      as their clinical features may overlap. Hence, to make a correct diagnosis and
      differentiate between CHS and GPS light microscopic examination of skin and hair
      shafts as well as peripheral blood smear evaluations should be done. In cases
      where the diagnosis is not possible chromosomal analysis for specific mutations
      can be done. In resource-poor settings where chromosomal analysis is not
      possible, and light microscopy findings are inconclusive, polarized microscopy
      can serve as a useful tool to distinguish between CHS and GPS. We report three
      cases with gray hair syndromes where the diagnosis on light microscopy and
      polarized microscopy of hair shaft correlated with the bone marrow examination
      findings and chromosomal analysis, thus emphasizing the importance of a
      noninvasive, cost-effective, and time-saving alternative in the diagnosis of
      these syndromes.

PMID- 28761266
TI  - Reply to: Hyperprolactinemia and Hirsutism in Patients without Polycystic Ovary
      Syndrome.

PMID- 28761267
TI  - Hair in the Mouth: A Rare Presentation.

PMID- 28761268
TI  - Burnt Matchstick Sign - A new Trichoscopic finding in Trichotillomania.

PMID- 28761269
TI  - Sushruta: The father of surgery.

PMID- 28761270
TI  - Medicinal plants and bone healing.
AB  - Fracture is defined as complete or incomplete separation in the continuity of
      bone Fracture healing is a complex physiological process that involves the
      coordinated participation of hematopoietic and immune cells within bone marrow.
      It conjunction with vascular and skeletal cell precursors it also includes
      mesenchymal stem cells which are recruited from the circulation and the
      surrounding tissues. It is estimated that 80% of the population in developing
      countries still rely on the traditional herbal medicines. Healing is practiced by
      people from all levels of society, who live and work in intimate relation with
      their environment. They range from bone setting, treatment of snake bite and
      mental disorders. Knowledge of Medicinal plants and their identification should
      be gain with the help of cowherds, hermits, hunters, forest dwellers and those
      who gather plants of forest for food. Sushruta Samita Sutrasthanam 36 V.10. Herbs
      can effective in reducing swelling pain and soreness of the fracture and al so
      speedy recovery of function. In last few decades there has been growing In
      alternative forms of therapy globally. Herbal medicines are currently in demand
      and their popularity is increasing.

PMID- 28761271
TI  - A comparative clinical evaluation of analgesic efficacy of Tapentadol and
      ketorolac in mandibular third molar surgery.
AB  - INTRODUCTION: The surgical removal of impacted mandibular third molars is one of
      the most commonly performed dentoalveolar procedures in oral and maxillofacial
      surgery and is associated with varying degrees of postoperative discomfort. Pain,
      trismus, and swelling are the most common postoperative complaints, and these
      influence a patient's quality of life in the days after surgery. MATERIALS AND
      METHODS: A comparative study of the 32 patients, 16 were allocated to receive
      ketorolac and 16 patients were allocated to receive tapentadol. As the data for
      this study were collected at different time points, analysis for the longitudinal
      study was done. The main outcome variable, pain level was measured in five
      ordered categories. As we had ordinal data in our study, we first checked for
      marginal homogeneity through Cochran-Mantel-Haenszel test. RESULTS: In the
      present study, the results show that there is no statistically significant
      difference between the two treatment groups (P = 0.1184). According to results,
      there is no significant group by time interaction, which means both drugs have
      shown almost equal efficacy at different time points. Similarly, there is no
      difference in efficacy of the two drugs across gender level. CONCLUSION: The
      present findings showed that there is no statistically significant difference
      between the two treatment groups, although ketorolac is more effective for
      immediate pain reduction than tapentadol. However, the overall reduction of pain
      using both groups has no significant difference.

PMID- 28761272
TI  - Efficacy of Murva (Sansevieria roxburghiana Schult. and Schult.f.) as a suture
      material in closure of incisions in third molar surgeries: A prospective study.
AB  - INTRODUCTION: Adequate closure of the surgical wound is one of the most important
      aspects of surgery; improper suturing techniques or improper suturing materials
      sometimes compromise the success of surgery. Many synthetic materials have
      replaced the natural materials, which were once used for suturing in the ancient
      era, and Murva is one of them. There are references of Murva (Sansevieria
      roxburghiana Schult. and Schult.f.) at various contexts of "Sushruta Samhita"
      where it has been used as a suture material. It is a xerophytic herbaceous plant
      occurring abundantly in the eastern coastal region of India. The aim of this
      study is to evaluate the efficacy of Murva fibers as a suturing material in
      closure of intraoral incision in third molar surgeries. MATERIALS AND METHODS:
      Fifty incisions (Wards incision) placed for the surgical removal of mandibular
      third molar were sutured with Murva, and follow-up was carried out
      postoperatively on 1st, 2nd, 3rd, and 7th day. Patients were evaluated for pain,
      swelling, bleeding, infection, wound dehiscence, local tissue irritation, and
      bacterial colonization. RESULTS: On various follow-ups, progressively significant
      and predictable healing was observed without any uneventful evidence. CONCLUSION:
      The use of Murva as a suture material proved to be effective in closure of
      intraoral incisions.

PMID- 28761273
TI  - A comparative evaluation of dental calcification stages and skeletal maturity
      indicators in North-Indian children.
AB  - BACKGROUND: Many researchers have reported relationships between the
      calcification stages of individual teeth and skeletal maturity. A few studies are
      available in the literature about Indian populations. In view of this fact, this
      study was conducted to investigate the relationship between the dental
      calcification stages and skeletal maturity stages among North-Indian individuals.
      The objective of this study was to determine whether dental calcification can be
      used as a first-level diagnostic tool for assessment of skeletal maturity.
      MATERIALS AND METHODS: The study participants included (60 males, 60 females)
      ranging from 7 to 13 years. A total of 120 dental panoramic radiographs and hand
      wrist radiographs were obtained and analyzed. Calcification stages of the
      mandibular dentition (canines, first premolars, second premolars, and second
      molars) were rated according to the system of Demirjian et al. Skeletal maturity
      indicators stages were determined using the Fishman method. RESULTS AND
      CONCLUSION: Bivarate correlation ranged from 0.58 to 0.75 for males and 0.73 to
      0.84 for females. Canine showed the highest correlation in males and second molar
      showed the highest correlation in females. Canine calcification Stage H represent
      prepeak of the pubertal growth spurt in male patients. Calcification Stage G for
      second molar represents the prepeak and Stage H represents the peak of pubertal
      growth spurt in females.

PMID- 28761274
TI  - Comparative evaluation of bite force analytical study following mandibular
      osteosysthesis using three-dimensional and conventional locking miniplates.
AB  - AIMS AND OBJECTIVES: The aim is to study the effectiveness of 2 mm three
      dimensional (3D) titanium miniplates and 2 mm conventional titanium miniplates in
      osteosynthesis of mandibular fractures by comparing the change in bite force.
      METHODOLOGY: The study comprised forty patients of age group 20-40 years,
      weighing 55-75 kg having mandibular fractures. Patients were randomly divided
      into two equal groups In Group A, twenty patients underwent osteosynthesis using
      3D titanium miniplates (2.0 mm system), whereas in Group B, twenty patients
      underwent osteosynthesis using conventional titanium miniplates (2.0 mm system).
      After fixation of fracture segments with miniplates, the patients were assessed
      on the basis of evaluation of bite force at incisor, right molar and left molar
      region after 1, 3, 6 , and 8 weeks. Comparison of change in bite force was done
      between Group A and Group B at different follow-ups at incisor, right molar, and
      left molar. RESULTS: Bite force recordings showed increasing values at subsequent
      follow-ups, corresponding to the healing of the fracture in both groups. At
      follow-up III (6 weeks) and IV (8 weeks), bite force values reached near to those
      in healthy individuals. A significant difference was observed in change in bite
      force of Group A and Group B at incisor left molar and right molar on subsequent
      followups. 3D titanium miniplate requires less surgical exposure of the
      underlying fracture site, with a minimal traction of the surrounding soft tissue.
      INTERPRETATION AND CONCLUSION: 3D miniplates in mandibular fractures are
      efficacious enough to bear masticatory loads during the osteosynthesis of
      fractures. It gives the advantage of greater stability, increased bite force,
      reduced implant material, and 3D stability.

PMID- 28761276
TI  - Efficacy of oral colchicine with intralesional hyaluronidase or triamcinolone
      acetonide in the Grade II oral submucous fibrosis.
AB  - BACKGROUND AND OBJECTIVES: Oral submucous fibrosis (OSMF) is a potentially
      malignant disorder of oral mucosa affecting mainly population in South and
      Southeast Asia. The aim of this study is to compare the effectiveness of oral
      colchicine with intralesional injection of hyaluronidase or injection
      triamcinolone acetonide in patients with Grade II OSMF. MATERIALS AND METHODS:
      The study included thirty patients of clinically diagnosed Grade II OSMF.
      Patients were divided randomly into two groups: Group A patients were treated by
      administrating tablet colchicine 0.5 mg twice daily with an intralesional
      injection of hyaluronidase 1500 IU with 0.5 ml of lignocaine hydrochloride at
      weekly interval for 12 weeks. Group B patients were treated by administering
      tablet colchicine 0.5 mg twice daily with an intralesional injection of
      triamcinolone acetonide 10 mg/ml at weekly interval for 12 weeks. Clinical
      diagnosis was based on burning sensation in mouth, blanching of mucosa, presence
      of vesicles or ulceration in oral cavity, and reduced mouth opening. Outcome
      assessment was done at intervals of 3 weeks, 6 weeks, 3 months, and 6 months.
      RESULTS: Improvement in mouth opening and reduction in burning sensation was seen
      more in Group A patients. Improvement in blanching of mucosa was seen in both the
      groups. CONCLUSION: In conclusion, use of injection hyaluronidase with oral
      colchicine gave better results in terms of increase in mouth opening and
      improvement in burning sensation without notable side effects. However, for a
      definite conclusion, further study with large sample size and long follow-up is
      required.

PMID- 28761277
TI  - Bilateral parotidomegaly as an initial manifestation of acute lymphoblastic
      leukemia in a child: A case report and review of literature.
AB  - The more common causes of parotid enlargement in children are infections and
      inflammatory conditions. Primary neoplasms of the parotid glands are rare in
      pediatric age group; however, secondary malignancies have been reported in
      survivors of childhood leukemia. The parotid glands have been the sites of
      relapses in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia.
      However, bilateral parotid involvement as an initial presentation of ALL is
      rarely reported. We present a case of an 8-year-old boy who presented with
      bilateral parotid enlargement as an initial manifestation of ALL. General
      physicians should be aware of this extramedullary presentation of acute leukemia
      when they see a child presenting with organomegaly or abnormal blood counts.

PMID- 28761275
TI  - Efficacy of arthrocentesis versus arthrocentesis with sodium hyaluronic acid in
      temporomandibular joint osteoarthritis: A comparison.
AB  - INTRODUCTION: Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative
      disease characterized by deterioration of articular tissue with concomitant
      osseous changes in the condyle and/or articular eminence, joint positive for TMJ
      noise with jaw movement or function, crepitus detected on palpation on opening,
      closing, right/left lateral, or protrusive movement. Hyaluronic acid (HA) is a
      polysaccharide of the family of glycosaminoglycans. HA has been shown to improve
      and restore normal lubrication in joint, provide nutrition to the avascular
      articulating disc, and stabilize the joint. MATERIALS AND METHODS: Twenty
      patients with OA of TMJ with age limit between 18 and 60 years of age were
      enrolled in this study. Patients were randomly divided into two groups, in which
      one group received arthrocentesis only, and another group received arthrocentesis
      plus intra-articular injection of sodium HA (0.5 ml) in superior joint space in a
      cycle of 5 weekly arthrocentesis (one per week). Patients were followed at
      regular interval of 1st day, 5th day, 7th day, 4 weeks, 6 weeks, and 12 weeks.
      Assessment of clinical outcome was done in terms of reduction in pain (visual
      analog scale score), maximum mouth opening (MMO) in millimeters, painful/pain
      free lateral or protrusive jaw movement, and clicking/crepitus in joint. RESULTS:
      Significant reduction in pain was observed in both the groups. MMO, lateral and
      protrusive movements improved significantly in both groups; however,
      arthrocentesis with sodium HA was superior to arthrocentesis alone. CONCLUSION:
      Combination of arthrocentesis with HA injection showed much better outcome than
      arthrocentesis alone.

PMID- 28761278
TI  - Unilateral condylar hyperplasia - A genetic link? Case reports.
AB  - Unilateral condylar hyperplasia is an uncommon condition with unknown etiology
      which causes overdevelopment of condyle leading to facial asymmetry, mandibular
      deviation, malocclusion, and articulation dysfunction. Two Indian families with
      unilateral condylar hyperplasia are presented where the similar abnormality was
      also detected in one of their parents. The condylar hyperplasia in these two
      families indicates that mandibular condylar hyperplasia could be genetic in
      origin.

PMID- 28761280
TI  - Recurrent keratocystic odontogenic tumor of right maxillary sinus involving the
      right infraorbital rim.
AB  - Keratocystic odontogenic tumor (KCOT) is a benign odontogenic tumor with an
      aggressive behavior and high recurrence rate. The most common site of
      predilection is the posterior mandible. In contrast, KCOTs occurring in the
      maxillary region are relatively rare. However, the maxillary involvement poses a
      greater and increased threat, due to proximity to vital structures such as
      maxillary sinus, orbital floor, and infratemporal fossa. This report presents
      such a case of KCOT involving the maxillary sinus eroding the floor of the orbit
      and provides an account of the factors that need to be considered during
      management.

PMID- 28761279
TI  - Role of sclerotherapy in management of vascular malformation in the maxillofacial
      region: Our experience.
AB  - The management of vascular anomalies is an extremely challenging area and is as
      divergent as the nature of lesions. Traditionally, embolization with the
      resection of the lesion has been used. The purpose of this report is to present
      cases treated successfully using sclerosing solution injections alone. Management
      of the vascular malformation using intralesional injections of sodium tetradecyl
      sulfate to the lesion is discussed. The procedure was performed two times at 2
      weeks interval. Complete resolution of the lesion was found following
      sclerotherapy. Conservative interventional management using intralesional
      injection of sclerosing solution was successful in treating vascular anomaly.

PMID- 28761281
TI  - Concomitant hypodontia and hyperdontia: A report of two cases.
AB  - "Concomitant hypodontia and hyperdontia" is a very rare dental anomaly of number,
      having a prevalence rate of 0.002%-3.1%. It describes the simultaneous presence
      of hypodontia or missing teeth and supernumerary teeth in the same individual. It
      represents the opposite forces of nature acting simultaneously. Two rare cases of
      this anomaly involving different jaws and a classification based on the
      literature review have been presented here.

PMID- 28761282
TI  - Verruciform xanthoma of the tongue.
AB  - Verruciform xanthoma is a benign, soft tissue lesion occurring on the orogenital
      mucosa. Presentation of oral lesions can be pink, yellow, or gray raised plaque
      or papule with granular, papillary, or verrucous in nature. There are many
      theories proposed for the etiopathogenesis of verruciform xanthoma. Clinical
      observations may be misguiding as the lesion resembles malignant and premalignant
      lesions. Histopathological confirmation is essential for diagnosis and avoiding
      radical surgery. Once excised, the lesion does not recur. Here, we present a case
      report of verruciform xanthoma of the tongue in a 50-year-old female patient.

PMID- 28761284
TI  - Common peroneal nerve palsy in maxillofacial surgery setting.
AB  - Common peroneal nerve palsy in maxillofacial surgery setting is an uncommon and
      rarely reported complication. A patient who developed common peroneal nerve palsy
      following reduction and fixation of pan facial fractures under general anesthesia
      is presented. The patient developed common peroneal nerve palsy on the second
      postoperative day. He recovered with conservative treatment after 3 months. The
      authors consider that the nerve palsy was a result of compression of common
      peroneal nerve related to patient positioning in the perioperative period.
      Patient- and surgery-related risk factors are also to be considered. Thus, for at
      risk patients, positioning is of utmost importance in both intra- and peri
      operative period.

PMID- 28761283
TI  - Report of a rare cyst at a rare site: Heterotopic gastrointestinal cyst partially
      lined with dermoid cyst epithelium.
AB  - Heterotopic gastrointestinal cysts (HGCs) of the oral cavity are rare benign
      lesions mimicking benign or malignant pathologies. These cysts are usually
      discovered during infancy but may not appear until well into adulthood. The
      epithelial lining of these cysts shows variable presentation with the presence of
      an enteric lining as an essential component. The histogenesis is related to
      entrapment of undifferentiated, noncommitted endoderm within the oral cavity
      during the 3rd - 4th week of fetal life. We report a rare case of oral HGC
      located at a very rare site, i.e., infratemporal fossa with histopathologic
      features that included portions resembling dermoid cyst also. Histopathology and
      etiopathogenesis of the lesion are discussed. Origin from misplacement of
      embryonic remnants, i.e., undifferentiated endodermal cells is suggested.

PMID- 28761285
TI  - Suppressive Effects of Mesenchymal Stem Cells in Adipose Tissue on Allergic
      Contact Dermatitis.
AB  - BACKGROUND: Allergic contact dermatitis (ACD), which is accelerated by interferon
      (IFN)-gamma and suppressed by interleukin (IL)-10 as regulators, is generally
      self-limited after removal of the contact allergen. Adipose tissue-derived
      multipotent mesenchymal stem cells (ASCs) potentially exert immunomodulatory
      effects. Considering that subcutaneous adipose tissue is located close to the
      site of ACD and includes mesenchymal stem cells (MSCs), the MSCs in adipose
      tissue could contribute to the self-limiting course of ACD. OBJECTIVE: The aims
      of the present study were to elucidate the effects of MSCs in adipose tissue on
      ACD and to examine any cytokine-mediated mechanisms involved. METHODS: Ear
      thickness in a C57BL/6 mouse model of ACD using contact hypersensitivity (CHS)
      elicited by 2,4,6-trinitro-1-chlorobenzene was evaluated as a marker of
      inflammation level. Five and nine mice were injected with ASCs and phosphate
      buffered saline (PBS), respectively. After ASC or PBS injection, real-time
      reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent
      assay were performed. RESULTS: Histology showed that CHS was self-limited and ear
      thickness was suppressed by ASCs in a dose-dependent manner. IFN-gamma expression
      in the elicited skin site and regional lymph nodes was significantly lower in ASC
      treated mice than in control mice. IL-10 expression did not differ between
      treated and control mice. The suppressive effects of ASCs on CHS response did not
      differ between IL-10 knock-out C57BL/6 mice and wild-type mice. CONCLUSION: The
      present findings suggest that MSCs in adipose tissue may contribute to the self
      limiting course of ACD through decreased expression of IFN-gamma, but not through
      increased expression of IL-10.

PMID- 28761286
TI  - House Dust Mite Sensitization Is Inversely Associated with Plasma 25
      Hydroxyvitamin D3 Levels in Patients with Severe Atopic Dermatitis.
AB  - BACKGROUND: The relationship between atopic dermatitis (AD) and low vitamin D
      levels has been studied. Emerging evidence has implicated vitamin D as a critical
      regulator of immunity, playing a role in both the innate and cell-mediated immune
      systems. However, the effect of vitamin D on house dust mite (HDM) sensitization
      in patients with AD has not been established. OBJECTIVE: We investigated the
      association between vitamin D levels and HDM sensitization according to AD
      severity. METHODS: In total, 80 patients (43 men and 37 women) with AD were
      included. We classified AD severity using Rajka and Langeland scores. Laboratory
      tests included serum 25-hydroxyvitamin D3, total immunoglobulin E (IgE), and
      specific IgE antibody titer against Dermatophagoides farinae and D.
      pteronyssinus. RESULTS: There were no differences in vitamin D levels between the
      mild or moderate AD and severe AD groups. In the severe AD group, high HDM
      sensitization group had lower serum vitamin D levels compared to low HDM
      sensitization group with statistical significance. In addition, a significant
      negative correlation was found between vitamin D levels and HDM sensitization in
      the severe AD group. CONCLUSION: Our results demonstrate that low vitamin D
      levels may link to high HDM sensitization in patients with the severe AD. Further
      elucidation of the role of vitamin D in HDM sensitization may hold profound
      implications for the prevention and treatment of AD.

PMID- 28761287
TI  - Adiponectin Upregulates Filaggrin Expression via SIRT1-Mediated Signaling in
      Human Normal Keratinocytes.
AB  - BACKGROUND: Filaggrin (FLG) is the major component of the epidermal granular
      layer and binds to and condenses the keratin cytoskeleton. FLG thus contributes
      to cell compaction and serves as a natural moisturizing factor by promoting
      unfolding and degradation into hygroscopic amino acids. Loss or downregulation of
      FLG has been shown to result in a weak stratum corneum, which causes water loss
      and increases the possibility of skin barrier-related seizure. Adiponectin
      (Acrp30) contributes to the functional recovery of somatic cells, including human
      normal epidermal keratinocytes (NHEKs). OBJECTIVE: To investigate the effect of
      Acrp30 in FLG expression and identifying its signal transduction mechanism.
      METHODS: Normal human keratinocytes were treated with Acrp30 and the levels of
      FLG were examined. Silent mating type information regulation 2 homolog (SIRT)
      targeting siRNA and aryl hydrocarbon receptor nuclear translocator (ARNT)
      targeting siRNA were used to identify the role of various signal transduction
      pathway components. RESULTS: Acrp30 upregulated SIRT1 and ARNT expression in
      NHEKs, resulting in increased FLG expression. Treatment with both SIRT1-targeting
      siRNA and ARNT-targeting siRNA blocked Acrp30 stimulation and silenced FLG
      expression. CONCLUSION: Adiponectin upregulates FLG expression through a SIRT1
      mediated pathway. Our results suggest that Acrp30 is a promising agent for skin
      barrier permeability improvement.

PMID- 28761288
TI  - Influence of Repeated Senna Laxative Use on Skin Barrier Function in Mice.
AB  - BACKGROUND: Senna, one of the major stimulant laxatives, is widely used for
      treating constipation. Chronic senna use has been reported to be associated with
      colonic disorders such as melanosis coli and/or epithelial hyperplasia. However,
      there is no obvious information on the influence of chronic senna use on organs
      except for the intestine. OBJECTIVE: To clarify the influence of senna laxative
      use on skin barrier function by repeated senna administration. METHODS: Eight
      week-old male hairless mice received senna (10 mg/kg/day) for 21 days. After
      administration, we evaluated transepidermal water loss (TEWL), and investigated
      the biomarkers in plasma and skin using protein analysis methods. RESULTS: Fecal
      water content on day seven was significantly increased; however, on day 21, it
      was significantly decreased after repeated senna administration. In the senna
      administered group, TEWL was significantly higher compared to the control on days
      seven and 21. Plasma acetylcholine concentration and NO2-/NO3- were increased on
      days seven and 21, respectively. In skin, tryptase-positive mast cells and
      inducible nitric oxide synthase (iNOS)-positive cells were increased on days
      seven and 21, respectively. The increase of TEWL on days seven and 21 was
      suppressed by the administration of atropine and N(G)-nitro-L-arginine methyl
      ester, respectively. CONCLUSION: It was suggested that diarrhea or constipation
      induced by repeated senna administration caused the impairment of skin barrier
      function. There is a possibility that this impaired skin barrier function
      occurred due to degranulation of mast cells via cholinergic signals or oxidative
      stress derived from iNOS.

PMID- 28761289
TI  - Gene Expression Analysis of Inflammatory Cytokines in Korean Psoriatic Patients.
AB  - BACKGROUND: Although phenotypic heterogeneity of psoriasis is suggested by the
      alternate activation of either T-helper (Th)1-related or Th17-related cytokines,
      little is known about the mRNA levels of inflammatory cytokines. OBJECTIVE: To
      investigate whether there is differential expression of Th1-related and Th17
      related inflammatory cytokine genes 1) between psoriatic patients and healthy
      controls, and 2) between patients with different psoriasis phenotypes. METHODS:
      Twenty-five patients with psoriasis (10 with guttate psoriasis and 15 with plaque
      psoriasis) and 5 healthy volunteers were enrolled in this study. The mRNA levels
      of circulating cytokines (interleukin [IL]-2, IL-12p40, interferon-gamma, IL-17A,
      IL-22, and IL-23R) were measured by real-time reverse transcription polymerase
      chain reaction. RESULTS: The comparison between psoriatic and healthy control
      samples revealed that IL-12p40, IL-17A, and IL-22 mRNA levels were significantly
      higher (approximately 4~6 folds) in the patients with psoriasis. The mRNA levels
      of these six cytokines in the blood did not differ between the guttate and plaque
      psoriasis groups. CONCLUSION: We found that the mRNA levels of blood inflammatory
      cytokines (IL-12p40, IL-17A, and IL-22) were significantly elevated in patients
      with psoriasis compared to the levels in healthy controls, but they did not
      significantly differ between patients with guttate and plaque type psoriasis.

PMID- 28761290
TI  - Beneficial Effect of Low Fluence 1,064 nm Q-Switched Neodymium:Yttrium-Aluminum
      Garnet Laser in the Treatment of Senile Lentigo.
AB  - BACKGROUND: Low fluence 1,064 nm Q-switched (QS) Neodymium:Yttrium-Aluminum
      Garnet (Nd:YAG) laser treatment, also known as laser toning, is widely used for
      pigmentary disorders. There has been no reliable evaluation of the effect of low
      fluence 1,064 nm QS Nd:YAG laser for senile lentigo. OBJECTIVE: To investigate
      the beneficial effect of low fluence 1,064 nm QS Nd:YAG laser in the treatment of
      senile lentigo on the face. METHODS: A retrospective review was conducted on
      patients treated only with repetitive low fluence 1,064 nm QS Nd:YAG laser. Among
      them, 12 patients with multiple senile lentigines before treatment were included.
      All side effects were recorded to assess the safety of the modality. RESULTS:
      Mean age was 56.1+/-7.8 years old and male-to-female ratio was 1:11. Mean
      treatment fluence was 1.62+/-0.16 J/cm2 and mean total treatment session was
      8.8+/-2.6. Mean interval period between each session was 28.0+/-11.4 days and
      mean treatment session to reach marked and near total improvement was 8.7+/-2.8.
      At the final visit, seven of 12 (58.3%) patients reached marked and near total
      improvement, and three of 12 (25.0%) reached moderate improvement. No side
      effects occurred. CONCLUSION: Repetitive low fluence 1,064 nm QS Nd:YAG laser
      treatment may be an effective and safe optional modality for senile lentigo.

PMID- 28761291
TI  - Various Dermatoses What the Patients with Cutaneous Melanoma Had Anxiety for the
      Recurrence during Postoperative Surveillance.
AB  - BACKGROUND: The incidence and mortality rates associated with cutaneous melanoma
      (CM) have steadily increased over the last 20 years. Even with successful
      treatment, melanoma patients usually experience substantial anxiety regarding the
      development of terrible recurrence. To date, few studies have investigated
      various dermatoses what the patients with CM had anxiety for the recurrence
      during postoperative surveillance (Dw). OBJECTIVE: To describe various Dw and to
      evaluate the risk of subsequent malignant skin disease in patients with CM.
      METHODS: We performed a prospective study between August 2002 and August 2015.
      RESULTS: Fifty-six patients presented with a total of 68 Dw. Among them,
      melanocytic nevus was the most common (n=27), followed by seborrheic keratosis
      (n=9) and CM recurrence (n=7). Approximately 5.6% of the lesions were diagnosed
      as malignant skin diseases. This was a single-center study, so the prevalence of
      malignant skin diseases following primary melanoma may not represent that of all
      patients with CM. CONCLUSION: The results of this study can be referred by
      dermatologists dealing with melanoma especially when CM patients have too
      excessive or unrealistic anxiety for melanoma recurrence during postoperative
      surveillance of CM. However, the importance of postoperative surveillance must
      still be emphasized because of real risk of melanoma recurrence and other
      malignant skin.

PMID- 28761292
TI  - Analysis of Serum Cytokine Profile in Pemphigus.
AB  - BACKGROUND: Pemphigus is a group of autoimmune blistering diseases affecting skin
      and mucous membranes. While pemphigus is an autoantibody mediated disease, the
      role of T cells and cytokines in the pathogenesis is being increasingly
      recognized. OBJECTIVE: This study was conducted to observe alterations in the
      serum cytokine levels of patients with pemphigus vulgaris (PV), pemphigus
      foliaceous (PF), paraneoplastic pemphigus (PNP) and compare with bullous
      pemphigoid (BP) and healthy subjects. METHODS: A total of 75 subjects (28 PV, 13
      PF, 7 PNP, 7 BP, and 20 healthy controls) were included, all patients in active
      disease state. Serum levels of interferon (IFN)-gamma, interleukin (IL)-4, IL-6,
      IL-17A, IL-10, tumor necrosis factor (TNF)-alpha, and IL-8 were measured by
      enzyme-linked immunosorbent assay. RESULTS: The median concentration of IFN-gamma
      was lower in PV and BP patients compared to control (0.77, 0.34 and 1.63 pg/ml,
      respectively). IL-6 and IL-10 was significantly higher in PNP patients compared
      to control (4.92 and 0.24 pg/ml for IL-6, 0.86 and <0.12 pg/ml for IL-10,
      respectively). IL-8 was increased significantly in PV and PNP patients compared
      with control (11.85, 31.5 and 8.31 pg/ml, respectively). For IL-4, IL-17A and TNF
      alpha, no significant difference was observed between the five groups.
      CONCLUSION: The decreased level of IFN-gamma in PV may imply suppressed Th1
      response in the active disease stage. A Th2 predominant response is suggested in
      the active stage of PNP, with elevated serum levels of IL-6 and IL-10. Increased
      level of proinflammatory cytokine IL-8 is observed in the sera of PV and PNP
      patients.

PMID- 28761293
TI  - Treatment and Classification of Nevus of Ota: A Seven-Year Review of a Single
      Institution's Experience.
AB  - BACKGROUND: Nevus of Ota (NO) is a relatively common pigmentary disorder in
      Asians. Tanino's classification is an old but tacit consensus to delineate the
      disease. Various treatment options have been presented. However, a few studies
      have been conducted on available laser options and current treatment strategies
      or the classification of NO. OBJECTIVE: To investigate current laser options and
      their effectiveness for the treatment of NO, contributing factors to clinical
      outcomes, and verification of classification. METHODS: A retrospective study of
      NO was conducted by reviewing medical charts and photographs of sixty-seven
      patients. Statistical analysis was used to compare excellent and poor outcomes
      and determine contributing factors. RESULTS: The median age of onset was below
      the age of 1 (interquartile range [IQR], 0~1). Tanino's and PUMCH classification
      systems failed to classify patients in 24 (35.8%) and 6 (9.0%) of patients,
      respectively. A 1,064 nm Q-switched Nd:YAG laser without additional lasers was
      used most frequently in 42 patients (62.7%). The frequency of treatment was 19.0
      (IQR, 10.0~23.0) in the cured group defined as subjects showing 95% improvement
      or above, compared to 10.0 (IQR, 6.25~13.75) in the unattained group defined as
      subjects showing less than 95% improvement (p=0.001). CONCLUSION: A 1,064 nm Q
      switched Nd:YAG laser is a reliable treatment armamentarium, functioning as a
      single infallible modality as well as a combination treatment modality for NO.
      Repetitive laser treatments without interruption seems to be the most suitable in
      clearing NO. The current classification systems of NO are defective. Thus, a new
      classification should be developed.

PMID- 28761294
TI  - Morphological Characteristics of Residual Skin Surface Components Collected from
      the Surface of Facial Skin in Women of Different Age.
AB  - BACKGROUND: Problems of skin aging and its prevention currently attract
      increasing attention with the growth of human life expectancy. The morphology of
      the stratum corneum (SC) is well known, but investigation of age-related changes
      of its structure is difficult in the absence of non-invasive sampling methods.
      The residual skin surface components (RSSC) that overlay the SC can be easily
      collected non-invasively. OBJECTIVE: The aim of this study was to examine
      morphology of RSSC samples collected from the surface of facial skin of healthy
      female volunteers of different age. METHODS: RSSC samples were non-invasively
      collected from 53 adult female volunteers (22 aged in the range 18~25 years and
      31 aged in the range 50~73 years). The samples were analysed microscopically.
      RESULTS: Distinct age-related changes were determined for lipid droplet size,
      corneocyte desquamation level and lipid crystal count. There was a significant
      (p=0.0006) decrease in lipid droplet size among older women. Similarly,
      significantly (p=0.0401) lower lipid crystal numbers were present in the older
      group. Conversely, corneocyte desquamation was significantly higher (p=0.0007) in
      older women. No age-related difference in microbial presence in the RSSC could be
      detected. Result patterns were generally similar to those previously found in
      male volunteers; however gender-related differences in the absolute values were
      revealed. CONCLUSION: Non-invasively collected RSSC samples allow identifying age
      related changes on facial skin surface. The results of this study highlight
      gender-dependence of distinct elements of age-associated impairment of epidermal
      barrier and can be employed for developing new approaches to prevent changes
      associated with skin aging.

PMID- 28761296
TI  - Primary Cutaneous Nocardiosis Caused by Nocardia takedensis.
AB  - Nocardia species are aerobic, gram-positive, filamentous, partially acid-fast
      actinomycetes which are found worldwide in soil and decaying organic plant
      matter. When they infect human beings, they generally enter through the
      respiratory tract and then disseminate systemically. Rarely has a primary
      infection occurred as the result of direct inoculation. Isolation of Nocardia
      from clinical specimens and identification of species are difficult. But, with
      the introduction of new genetic technologies, reports of novel species of
      Nocardia have increased. We describe a case of cutaneous nocardiosis caused by
      Nocardia takedensis in an 87-year-old woman who was diagnosed by bacterial
      culture and 16S ribosomal RNA sequencing. N. takedensis has been described as a
      new species. This report describes the first clinical isolate of N. takedensis
      from a skin specimen in Korea.

PMID- 28761297
TI  - Pyoderma Gangrenosum in a Patient with X-Linked Agammaglobulinemia.
AB  - X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused
      by germline mutations of B-cell tyrosine kinase (BTK) gene. It is characterized
      by decreased serum immunoglobulins levels and circulating mature B cells. This
      defect in humoral immunity leads to increased susceptibility to infection.
      Pyoderma gangrenosum (PG) is an uncommon, ulcerating, neutrophilic dermatosis.
      Here we report PG in an 8-year-old patient with XLA. The patient received
      intravenous immunoglobulin treatment in conjunction with prednisone and topical
      application of 0.03% tacrolimus ointment and the ulcer was almost completely
      healed in the 2 weeks of follow-up. The coexistence has been rarely reported. XLA
      may be a possible cofactor in the pathogenesis of PG.

PMID- 28761298
TI  - Three Cases of Autoimmune Progesterone Dermatitis.
AB  - Autoimmune progesterone dermatitis is a rare cyclic premenstrual reaction to
      progesterone produced during the luteal phase of the menstrual cycle. The
      clinical symptoms of autoimmune progesterone dermatitis overlap with other forms
      of dermatosis such as erythema multiforme, eczema, fixed drug eruption,
      urticaria, and angioedema. We experienced 3 cases of autoimmune progesterone
      dermatitis. All patients had a recurrent history of monthly skin eruptions. Skin
      lesions normally began a few days before menstruation and resolved a few days
      later. Patients were confirmed to have autoimmune progesterone dermatitis by the
      results of the progesterone intradermal test. All three patients had different
      clinical findings such as erythema annulare centrifugum, urticaria, contact
      dermatitis, and rosacea. Because patients presented with variable clinical
      manifestations, they could have been easily misdiagnosed. The patients were
      treated with oral contraceptive, antihistamine and steroids for symptom control.
      We propose that dermatologists should consider autoimmune progesterone dermatitis
      in cases of recurrent cyclic skin eruptions in female patients. Further, if this
      condition is suspected, thorough history taking including that on menstrual cycle
      and intradermal progesterone test should be performed.

PMID- 28761295
TI  - The Clinical Profile of Patients with Psoriasis in Korea: A Nationwide Cross
      Sectional Study (EPI-PSODE).
AB  - BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease
      affecting multiple aspects of patients' lives. Its epidemiology varies
      regionally; however, nationwide epidemiologic data on psoriasis depicting profile
      of Korean patients has not been available to date. OBJECTIVE: To understand
      nationwide epidemiologic characteristics and clinical features of adult patients
      with psoriasis visited university hospitals in Korea. METHODS: This multicenter,
      non-interventional, cross-sectional study recruited 1,278 adult patients with
      psoriasis across 25 centers in Korea in 2013. Various clinical data including
      PASI, BSA, DLQI, SF-36 and PASE were collected. RESULTS: A total of 1,260
      patients completed the study (male:female=1.47:1). The mean age was 47.0 years
      with a distribution mostly in the 50s (24.9%). Early onset (<40 years) of
      psoriasis accounted for 53.9% of patients. The mean disease duration was 109.2
      months; mean body mass index was 23.9 kg/m2; and 12.7% of patients had a family
      history of psoriasis. Plaque and guttate types of psoriasis accounted for 85.8%
      and 8.4%, respectively. Patients with PASI >=10 accounted for 24.9%; patients
      with body surface area >=10 were 45.9%. Patients with DLQI >=6 accounted for
      78.8%. Between PASI <10 and PASI >=10 groups, significant difference was noted in
      age at diagnosis, disease duration, blood pressure, waist circumference of
      female, and treatment experiences with phototherapy, systemic agents, and
      biologics. CONCLUSION: This was the first nationwide epidemiologic study of
      patients with psoriasis in Korea and provides an overview of the epidemiologic
      characteristics and clinical profiles of this patient population.

PMID- 28761299
TI  - Cutaneous Plasmacytoma: Metastasis of Multiple Myeloma at the Fracture Site.
AB  - Multiple myeloma (MM) can be defined as a malignancy with monoclonal plasma cell
      proliferation. A 66-year-old man presented with pruritic erythematous to purplish
      plaque grouped nodule with black pigmentations and purpura on the right forearm.
      The patient was diagnosed with MM about five years prior to the visit at our
      hospital. Erythematous plaque on his right arm grew rapidly in size over one
      month and appeared about seven months after the fracture surgery. Skin biopsy
      showed multiple plasma cell infiltration with monoclonality for lambda light
      chain, which was consistent with cutaneous plasmacytoma. The patient refused to
      be treated and died two months later. We herein report an interesting case of
      cutaneous plasmacytoma at the surgical site of fracture repair.

PMID- 28761300
TI  - Lobulated Bowen's Disease with a Clear Cell Change.
AB  - Bowen's disease usually manifests as a slowly enlarging erythematous scaly patch
      or plaque. An uncommon variant of Bowen's disease showing a verrucous appearance
      has been reported and a distinct variant with a prominent clear cell change on
      histopathology, in addition to a verrucous surface change, was also reported. We
      describe novel form of Bowen's disease having a cerebriform appearance and
      showing histopathologically a significant clear cell change and propose that the
      clinical term "lobulated Bowen's disease" would be compatible for the description
      of this unique clinical variant. From a histopathological point of view, the
      precise definition and etiopathogenesis of the clear cell change in Bowen's
      disease should be elucidated.

PMID- 28761301
TI  - A Case of Nail Psoriasis Improved by Treatment with Golimumab in a Psoriatic
      Arthritis Patient.

PMID- 28761302
TI  - Reactivation of Herpes Simplex Virus Secondary to Excimer Laser Treatment in a
      Patient with Vitiligo.

PMID- 28761303
TI  - Neutrophilic Dermatosis of the Palms in Association with Myelodysplastic
      Syndrome.

PMID- 28761304
TI  - Fibro-Osseous Pseudotumor of the Digit Presenting as an Enlarging Erythematous
      Subungual Nodule.

PMID- 28761305
TI  - A Case of Wolf's Isotopic Response Presenting as Bullous Pemphigoid.

PMID- 28761306
TI  - Blastic Plasmacytoid Dendritic Cell Neoplasm Presenting as Erythematous Nodules
      with Gallbladder Involvement.

PMID- 28761307
TI  - Two Cases of Successful Treatment of Refractory Chronic Inflammatory Skin
      Disease, Atopic Dermatitis and Psoriasis with Oral Alitretinoin.

PMID- 28761308
TI  - Porokeratosis Ptychotropica Coexisting with Tinea Corporis.

PMID- 28761310
TI  - Scar Sarcoidosis Developed after Blepharoplasty in Acute Lymphoblastic Leukemia
      Patient.

PMID- 28761309
TI  - Glyceraldehyde-Derived Advanced Glycation End Products Accumulate Faster Than
      Nepsilon-(Carboxymethyl) Lysine.

PMID- 28761311
TI  - The Association between Exercise and Androgenetic Alopecia: A Survey-Based Study.

PMID- 28761312
TI  - Superficial Epithelioma with Sebaceous Differentiation Presented as a Yellow
      Plaque.

PMID- 28761313
TI  - A Case of Eccrine Spiradenoma: A Rarely Seen Soft Tissue Tumor on the Extensor
      Surface of Arm.

PMID- 28761314
TI  - A Case of Bowen's Disease Successfully Treated with Ingenol Mebutate Gel.

PMID- 28761315
TI  - Five-Alpha Reductase Inhibitor and Breast Cancer Risk in Men: A Systematic
      Review.

PMID- 28761316
TI  - Asymptotics for a Class of Dynamic Recurrent Event Models.
AB  - Asymptotic properties, both consistency and weak convergence, of estimators
      arising in a general class of dynamic recurrent event models are presented. The
      class of models take into account the impact of interventions after each event
      occurrence, the impact of accumulating event occurrences, the induced informative
      and dependent right-censoring mechanism due to the data-accrual scheme, and the
      effect of covariate processes on the recurrent event occurrences. The class of
      models subsumes as special cases many of the recurrent event models that have
      been considered in biostatistics, reliability, and in the social sciences. The
      asymptotic properties presented have the potential of being useful in developing
      goodness-of-fit and model validation procedures, confidence intervals and
      confidence bands constructions, and hypothesis testing procedures for the finite-
      and infinite-dimensional parameters of a general class of dynamic recurrent event
      models, albeit the models without frailties.

PMID- 28761317
TI  - Physical disruption of cell-cell contact induces VEGF expression in RPE cells.
AB  - PURPOSE: To investigate the role of RPE cell-cell contact in vascular endothelial
      growth factor (VEGF) protein expression in cultures of primary human RPE (hRPE)
      cells and a human RPE cell line (ARPE-19). METHODS: Two in vitro methods,
      scratching and micropatterning, were used to control the physical dissociation of
      RPE cell-cell junctions. Scratching was performed by scoring monolayers of RPE
      cells with a cell scraper. Micropatterning was achieved by using a stencil
      patterning method. Extracellular VEGF expression was assessed by using an enzyme
      linked immunosorbent assay (ELISA) kit. Immunocytochemistry (ICC) was performed
      to visualize the expression and localization of VEGF and intercellular proteins
      zonula occludens-1 (ZO-1), N-cadherin, beta-catenin, and claudin-1 in RPE
      cultures. RESULTS: Higher expression of VEGF protein by cells on the edges of the
      scratched RPE layers was confirmed with ICC in short-term (1 day after
      confluency) and long-term (4 weeks after confluency) cultures. According to the
      ICC results, ZO-1, N-cadherin, beta-catenin, and claudin-1 successfully localized
      to cell-cell junctions in long-term cultures of ARPE-19 and hRPE cells. However,
      unlike N-cadherin, beta-catenin, and claudin-1, only ZO-1 localized junctionally
      in short-term cultures of both cell types. Moreover, removing cell-cell junctions
      by scratching resulted in the delocalization of ZO-1 from tight junctions to the
      cytoplasm. The loss of tight junction formation and the accumulation of ZO-1 in
      the cytoplasm correlated with increased VEGF expression. Micropatterning RPE
      cells on different sized circular patterns produced varying concentrations of
      cells with lost cell-cell junctions. When fewer cells formed intercellular
      junctions, increased extracellular VEGF secretion was observed from the ARPE-19
      and hRPE cells. CONCLUSIONS: VEGF expression increases after physical disruption
      of RPE cell-cell connections. This increase in VEGF expression correlates with
      the loss of intercellular junctions and the localization of ZO-1 in the cytoplasm
      of RPE cells.

PMID- 28761318
TI  - Parkin overexpression protects retinal ganglion cells against glutamate
      excitotoxicity.
AB  - PURPOSE: To investigate the role of parkin in regulating mitochondrial
      homeostasis of retinal ganglion cells (RGCs) under glutamate excitotoxicity.
      METHODS: Rat RGCs were purified from dissociated retinal tissue with a modified
      two-step panning protocol. Cultured RGCs were transfected with parkin using an
      adenovirus system. The distribution and morphology of mitochondria in the RGCs
      were assessed with MitoTracker. The expression and distribution of parkin and
      optineurin proteins were measured with western blot analysis and
      immunofluorescence. Cytotoxicity of RGCs was evaluated by measuring lactate
      dehydrogenase (LDH) activity. Mitochondrial membrane potential was determined
      with the JC-1 assay. The expression of Bax and Bcl-2 were measured with western
      blot analysis. RESULTS: In the presence of glutamate-induced excitotoxicity, the
      number of mitochondria in the axons of the RGCs was predominantly increased, and
      the mitochondrial membrane potential in RGCs was depolarized. The expression of
      the parkin and optineurin proteins was upregulated and distributed mostly in the
      axons of the RGCs. Overexpression of parkin stabilized the mitochondrial membrane
      potential of RGCs, decreased cytotoxicity and apoptosis, attenuated the
      expression of Bax, and promoted the expression of optineurin under glutamate
      excitotoxicity. CONCLUSIONS: Overexpression of parkin exerted a significant
      protective effect on cultured RGCs against glutamate excitotoxicity.
      Interventions to alter the parkin-mediated mitochondria pathway may be useful in
      protecting RGCs against excitotoxic RGC damage.

PMID- 28761319
TI  - The expression profile of developmental stage-dependent circular RNA in the
      immature rat retina.
AB  - PURPOSE: Physiologic neuronal apoptosis, which facilitates the developmental
      maturation of the nervous system, is regulated by neuronal activity and gene
      expression. Circular RNA (circRNA), a class of non-coding RNA, regulates RNA and
      protein expression. As the relationship between circRNA and apoptosis is unknown,
      we explored changes in expression patterns of circRNA during physiologic neuronal
      apoptosis. METHODS: High-throughput sequencing was used to explore changes in the
      expression of circRNA in the postnatal developing rat retina. Neuronal apoptosis
      was determined with immunohistochemistry and terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) in the rat retinal ganglion cell
      layer. RESULTS: In total, 2,654, 7,201, and 5,628 circRNA species were detected
      in the postnatal day (P)3, P7, and P12 rat retina, respectively. Of these circRNA
      species, 1,371 changed statistically significantly between P3 and P7 and 1,112
      changed statistically significantly between P7 and P12. Normal developmental
      apoptosis, measured with the ratio of apoptotic (caspase-3- or TUNEL-positive)
      cells to normal cells, showed an increase from P3 to P7 and then a reduction from
      P7 to P12. In addition, 15 circRNAs whose host genes were associated with
      apoptosis were differentially expressed during the early development period.
      CONCLUSIONS: These results associate circRNAs with neuronal apoptosis, providing
      potential mechanisms and treatment targets for physiologic and drug-induced
      apoptosis in the developing nervous system.

PMID- 28761320
TI  - Next-generation sequencing to solve complex inherited retinal dystrophy: A case
      series of multiple genes contributing to disease in extended families.
AB  - PURPOSE: With recent availability of next-generation sequencing (NGS), it is
      becoming more common to pursue disease-targeted panel testing rather than
      traditional sequential gene-by-gene dideoxy sequencing. In this report, we
      describe using NGS to identify multiple disease-causing mutations that contribute
      concurrently or independently to retinal dystrophy in three relatively small
      families. METHODS: Family members underwent comprehensive visual function
      evaluations, and genetic counseling including a detailed family history. A
      preliminary genetic inheritance pattern was assigned and updated as additional
      family members were tested. Family 1 (FAM1) and Family 2 (FAM2) were clinically
      diagnosed with retinitis pigmentosa (RP) and had a suspected autosomal dominant
      pedigree with non-penetrance (n.p.). Family 3 (FAM3) consisted of a large family
      with a diagnosis of RP and an overall dominant pedigree, but the proband had
      phenotypically cone-rod dystrophy. Initial genetic analysis was performed on one
      family member with traditional Sanger single gene sequencing and/or panel-based
      testing, and ultimately, retinal gene-targeted NGS was required to identify the
      underlying cause of disease for individuals within the three families. Results
      obtained in these families necessitated further genetic and clinical testing of
      additional family members to determine the complex genetic and phenotypic
      etiology of each family. RESULTS: Genetic testing of FAM1 (n = 4 affected; 1
      n.p.) identified a dominant mutation in RP1 (p.Arg677Ter) that was present for
      two of the four affected individuals but absent in the proband and the presumed
      non-penetrant individual. Retinal gene-targeted NGS in the fourth affected family
      member revealed compound heterozygous mutations in USH2A (p. Cys419Phe,
      p.Glu767Serfs*21). Genetic testing of FAM2 (n = 3 affected; 1 n.p.) identified
      three retinal dystrophy genes (PRPH2, PRPF8, and USH2A) with disease-causing
      mutations in varying combinations among the affected family members. Genetic
      testing of FAM3 (n = 7 affected) identified a mutation in PRPH2 (p.Pro216Leu)
      tracking with disease in six of the seven affected individuals. Additional
      retinal gene-targeted NGS testing determined that the proband also harbored a
      multiple exon deletion in the CRX gene likely accounting for her cone-rod
      phenotype; her son harbored only the mutation in CRX, not the familial mutation
      in PRPH2. CONCLUSIONS: Multiple genes contributing to the retinal dystrophy
      genotypes within a family were discovered using retinal gene-targeted NGS.
      Families with noted examples of phenotypic variation or apparent non-penetrant
      individuals may offer a clue to suspect complex inheritance. Furthermore, this
      finding underscores that caution should be taken when attributing a single gene
      disease-causing mutation (or inheritance pattern) to a family as a whole.
      Identification of a disease-causing mutation in a proband, even with a clear
      inheritance pattern in hand, may not be sufficient for targeted, known mutation
      analysis in other family members.

PMID- 28761321
TI  - Sequence variants in four genes underlying Bardet-Biedl syndrome in
      consanguineous families.
AB  - PURPOSE: To investigate the molecular basis of Bardet-Biedl syndrome (BBS) in
      five consanguineous families of Pakistani origin. METHODS: Linkage in two
      families (A and B) was established to BBS7 on chromosome 4q27, in family C to
      BBS8 on chromosome 14q32.1, and in family D to BBS10 on chromosome 12q21.2.
      Family E was investigated directly with exome sequence analysis. RESULTS: Sanger
      sequencing revealed two novel mutations and three previously reported mutations
      in the BBS genes. These mutations include two deletions (c.580_582delGCA,
      c.1592_1597delTTCCAG) in the BBS7 gene, a missense mutation (p.Gln449His) in the
      BBS8 gene, a frameshift mutation (c.271_272insT) in the BBS10 gene, and a
      nonsense mutation (p.Ser40*) in the MKKS (BBS6) gene. CONCLUSIONS: Two novel
      mutations and three previously reported variants, identified in the present
      study, further extend the body of evidence implicating BBS6, BBS7, BBS8, and
      BBS10 in causing BBS.

PMID- 28761322
TI  - Optimization of a genotyping screening based on hydrolysis probes to detect the
      main mutations related to Leber hereditary optic neuropathy (LHON).
AB  - PURPOSE: Leber hereditary optic neuropathy (LHON) is a mitochondrial inherited
      disease characterized by bilateral vision problems, such as reduced visual
      acuity, dyschromatopsia, and central or centrocecal scotoma. Of these cases, 95%
      are caused by three mutations in mitochondrial DNA (mtDNA): m.G11778A, followed
      by m.T14484C and m.G3460A. The remaining 5% of cases of LHON are caused by rare
      mutations also present in mtDNA. Although conventional molecular tools for
      molecular screening of LHON are becoming popular, in most cases these tools are
      still expensive and time-consuming and are difficult to reproduce. Therefore, to
      meet the need for more accurate, faster, and cheaper techniques for molecular
      screening, as well as make it more accessible, we used the high-throughput method
      TaqMan(r) OpenArrayTM Genotyping platform for developing a customized high
      throughput assay for the three main mutations related to LHON. METHODS: The assay
      was performed for 87 individuals diagnosed with LHON or acquired optic neuropathy
      of unknown origin. The three main mutations were screened using the customized
      assay with the TaqMan(r) OpenArrayTM Genotyping platform, and all reactions were
      performed in triplicate. The positive and negative results were revalidated with
      restriction fragment length polymorphism PCR (RFLP-PCR) and Sanger sequencing.
      RESULTS: The main mutations related to LHON were detected in 34 patients with
      genotyping reactions, of which 27 cases had the m.G11778A mutation, and seven had
      the m.T14484C mutation. CONCLUSIONS: The TaqMan(r) OpenArrayTM Genotyping
      platform was shown to be an effective tool for molecular screening of the most
      common mutations related to LHON without presenting false positive or negative
      results for the analyzed mutations. In addition, this tool can be considered a
      cheaper, faster, and more accurate alternative for molecular screening of LHON
      mutations than PCR and Sanger sequencing, as 94 genotyping reactions can be
      performed within 6 h and specific TaqMan probes are used.

PMID- 28761323
TI  - The comparative safety of genipin versus UVA-riboflavin crosslinking of rabbit
      corneas.
AB  - PURPOSE: To investigate, after 24 h, the safety of genipin or ultraviolet A (UVA)
      riboflavin crosslinking of keratocytes and endothelial cells. METHODS: Fifteen
      New Zealand white rabbits were selected and divided into a PBS group (five
      rabbits), a 0.2% genipin crosslinking (GP-CXL) group (five rabbits), and a UVA
      riboflavin crosslinking (UVA-CXL) group (five rabbits). In the GP-CXL and PBS
      groups, 0.2% genipin or PBS was applied to the corneal surface of the right eyes.
      In the UVA-CXL group, a clinical crosslinking procedure was used. Before and
      after surgery, the operated eyes of each group were characterized with confocal
      microscopy, and the corneal buttons were excised for endothelium staining and
      electron microscopy. RESULTS: The corneal endothelial cell density of the GP-CXL,
      UVA-CLX, and PBS groups changed. There was a statistically significant difference
      in thickness and changes in corneal endothelial cell density between the UVA-CXL
      group and the PBS group (p<0.05), and between the UVA-CXL group and the GP-CXL
      group (p<0.05), but no statistically significant difference between the GP-CXL
      group and the PBS group. Confocal microscopy, transmission electron microscopy,
      and hematoxylin and eosin staining showed that there was keratocyte apoptosis in
      the anterior and middle stroma and endothelial cell damage in the UVA-CXL group.
      In the GP-CXL group, only active keratocytes were found and minimal endothelial
      cell damage. CONCLUSIONS: Treatment of rabbit corneas with 0.2% genipin showed
      minimal toxicity toward keratocytes and endothelial cells. Genipin is safer than
      UVA-CXL for crosslinking of thin corneas.

PMID- 28761324
TI  - ARMS2 variants may predict the 3-year outcome of photodynamic therapy for wet age
      related macular degeneration.
AB  - PURPOSE: To determine the association of age-related maculopathy susceptibility2
      (ARMS2) gene polymorphisms with the 3-year outcomes of photodynamic therapy (PDT)
      in wet age-related macular degeneration (wet AMD). METHODS: The single nucleotide
      polymorphism (SNP) at rs10490924 in the ARMS2 gene of 65 patients with wet AMD
      who underwent PDT was genotyped using the TaqMan assay. The clinical
      characteristics and the outcomes of PDT were compared among the three genotypes
      at rs10490924. A multivariate regression analysis was performed to evaluate the
      influence of the clinical cofactors on the association of rs10490924 with the
      visual outcome at 36 months after the first PDT. RESULTS: A significant
      difference was found among the genotypes in the age and the baseline lesion size.
      The patients with the GG genotype showed a significant improvement in vision, and
      the patients with the TT genotype showed a significant worsening of vision at all
      time points measured after the initial PDT. In the multivariate regression
      analysis, the number of the G allele at rs10490924 was associated with a
      significantly greater improvement in the baseline best-corrected visual acuity
      (BCVA) at 36 months after the first PDT. CONCLUSIONS: ARMS2 variants are likely
      associated with the 3-year outcomes of PDT in patients with wet AMD.

PMID- 28761325
TI  - Taxifolin protects RPE cells against oxidative stress-induced apoptosis.
AB  - PURPOSE: Oxidative stress-induced damage to RPE cells has been suggested to be an
      important factor in the pathogenesis of age-related macular degeneration.
      Taxifolin, a flavonol, has been shown to exhibit significant antioxidant
      properties. The purpose of this study was to investigate the potential protective
      effects of taxifolin on RPE cells cultured under oxidative stress conditions and
      to elucidate the underlying mechanisms. METHODS: Human RPE (ARPE-19) cells were
      treated with different concentrations of taxifolin and 0.4 mM of H2O2 for 24 h.
      Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Apoptosis was quantitatively measured by
      annexin V/propidium iodide double staining, and the expression levels of poly
      (ADP-ribose) polymerase (PARP) were evaluated by western blotting. Reactive
      oxygen species (ROS) were measured using a commercially available ROS detection
      system. The expressions of phase II enzymes, including NAD(P)H quinine
      oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase
      modifier (GCLM) and catalytic (GCLC) subunits, were examined using real-time PCR
      and western blotting. The nuclear localization of the nuclear factor (erythroid
      derived 2)-like 2 (NRF2) protein was detected by western blotting. Results:
      Taxifolin clearly inhibited the decrease in H2O2-induced cell viability, cell
      apoptosis, and intracellular ROS generation. In addition, taxifolin inhibited the
      H2O2-induced PARP cleavage. Moreover, treatment with taxifolin activated mRNA and
      the protein expression of NRF2 by inducing the translocation of NRF2 to the
      nucleus. Consequently, the mRNA and protein levels of the phase II enzymes NQO1,
      HO-1, GCLM, and GCLC increased. Conclusions: Taxifolin was shown to protect RPE
      cells against oxidative stress-induced apoptosis. The potential mechanism appears
      to involve the activation of NRF2 and the phase II antioxidant enzyme system.

PMID- 28761326
TI  - Concentrations of MUC16 and MUC5AC using three tear collection methods.
AB  - PURPOSE: To determine the optimal tear collection method for analysis of ocular
      surface mucins MUC5AC and MUC16. METHODS: Fifteen subjects without ocular surface
      disease were recruited. Subjects presented for tear collection on three separate
      days for three different tear collection methods with the order of method
      randomized. Methods used to collect tears from right and left eyes included
      Schirmer's strip, basal tear collection, and flush tear collection. All samples
      from the right eyes were individually analyzed for MUC5AC whereas the left eye
      samples were individually analyzed for MUC16. For each individual sample, 10 MUg
      of protein were loaded per lane into a 1% (w/v) agarose gel and run in
      electrophoresis buffer for 2 h. After overnight capillary transfer, membranes
      were incubated with either MUC5AC antibody CLH2 or MUC16 antibody OC125 for
      western blot analysis. Blots were developed with enhanced chemiluminescence (ECL)
      and signals captured with the Odyssey Fc (LI-COR). The relative amounts of MUC5AC
      and MUC16 were quantified with densitometry using software and compared for
      statistically significant differences between tear collection methods using the
      Kruskal-Wallis test in SPSS 22 and GraphPad Prism 7.02. Dunn's multiple
      comparisons test was used for pairwise post-hoc comparisons. RESULTS: Samples
      containing less than 10 MUg of total protein were not used for analysis which
      left eight samples (out of 45) unusable. The calculated MUC5AC median signal
      intensities from Schirmer's strip, basal tears, and flush tears were 2.86 (n =
      15, the interquartile range [IQR] = 2.54-3.21), 1.65 (n = 14, IQR = 1.34-3.1),
      and 1.67 (n = 9, IQR = 1.42-1.72), respectively (H = 9.5, p = 0.009). Post-hoc
      pairwise comparisons showed a statistically significant difference between
      Schirmer's strip and flush tears (p = 0.01). The calculated MUC16 median signal
      intensities from Schirmer's strip, basal tears, and flush tears were 1.88 (n =
      14, IQR = 1.43-2.61), 5.24 (n = 15, IQR = 4.16-6.21), and 2.45 (n = 7, IQR = 1.85
      2.48), respectively (H = 18.1, p = 0.001). Post-hoc pairwise comparison showed
      statistically significant differences between basal tears and Schirmer's strip (p
      = 0.0003) and between basal tears and flush tears (p = 0.006). CONCLUSIONS:
      MUC5AC and MUC16 are present in human tear fluid and can be captured using
      various tear collection methods. Although basal tear collection yielded the
      highest relative concentration of MUC16, Schirmer's strip tear collection yielded
      the highest MUC5AC concentration. Therefore, the tear collection method chosen
      depends on the mucin of interest.

PMID- 28761328
TI  - Training time and quality of smartphone-based anterior segment screening in rural
      India.
AB  - OBJECTIVE: We aimed at evaluating the ability of individuals without
      ophthalmologic training to quickly capture high-quality images of the cornea by
      using a smartphone and low-cost anterior segment imaging adapter (the "EyeGo"
      prototype). METHODS: Seven volunteers photographed 1,502 anterior segments from
      751 high school students in Varni, India, by using an iPhone 5S with an attached
      EyeGo adapter. Primary outcome measures were median photograph quality of the
      cornea and anterior segment of the eye (validated Fundus Photography vs
      Ophthalmoscopy Trial Outcomes in the Emergency Department [FOTO-ED] study; 1-5
      scale; 5, best) and the time required to take each photograph. Volunteers were
      surveyed on their familiarity with using a smartphone (1-5 scale; 5, very
      comfortable) and comfort in assessing problems with the eye (1-5 scale; 5, very
      comfortable). Binomial logistic regression was performed using image quality (low
      quality: <4; high quality: >=4) as the dependent variable and age, comfort using
      a smartphone, and comfort in assessing problems with the eye as independent
      variables. RESULTS: Six of the seven volunteers captured high-quality (median
      >=4/5) images with a median time of <=25 seconds per eye for all the eyes
      screened. Four of the seven volunteers demonstrated significant reductions in
      time to acquire photographs (P1=0.01, P5=0.01, P6=0.01, and P7=0.01), and three
      of the seven volunteers demonstrated significant improvements in the quality of
      photographs between the first 100 and last 100 eyes screened (P1<0.001, P2<0.001,
      and P6<0.01). Self-reported comfort using a smartphone (odds ratio [OR] =1.25;
      95% CI =1.13 to 1.39) and self-reported comfort diagnosing eye conditions (OR
      =1.17; 95% CI =1.07 to 1.29) were significantly associated with an ability to
      take a high-quality image (>=4/5). There was a nonsignificant association between
      younger age and ability to take a high-quality image. CONCLUSION: Individuals
      without ophthalmic training were able to quickly capture a high-quality magnified
      view of the anterior segment of the eye by using a smartphone with an attached
      imaging adapter.

PMID- 28761327
TI  - Expression and role of interleukin-9 in Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disease that
      can lead to blindness. This study was designed to investigate whether interleukin
      (IL)-9 plays a role in the development of VKH disease. METHODS: IL-9, IL-17, and
      interferon (IFN)-gamma levels, present in the supernatants of cultured peripheral
      blood mononuclear cells (PBMCs) and CD4+T cells, were assessed with enzyme-linked
      immunosorbent assay. IL-9 mRNA expression in PBMCs was measured with real-time
      quantitative PCR. The proliferation of PBMCs in response to different doses of
      recombinant human IL-9 (rIL-9) was measured using the Cell Counting Kit-8 assay.
      RESULTS: IL-9 mRNA levels in PBMCs were statistically significantly elevated in
      patients with active VKH disease compared to those in patients with inactive VKH
      disease (p<0.05) and normal controls (p<0.05). Statistically significantly higher
      expression of IL-9 was observed in the supernatants of stimulated PBMCs (p<0.01)
      and CD4+ T cells (p<0.01) from patients with active VKH disease compared to that
      in cells from patients with inactive VKH disease and normal controls. rIL-9 at a
      concentration of 100 ng/ml did not induce proliferation of PBMCs (p>0.05). After
      the PBMCs and CD4+ T cells were stimulated with rIL-9 (100 ng/ml), the secretion
      of IL-17 was increased statistically significantly (p<0.05), whereas the level of
      IFN-gamma was not statistically significantly altered (p>0.05). CONCLUSIONS:
      These findings suggest that IL-9 is involved in the pathogenesis of VKH disease,
      and that IL-9 might also enhance the inflammatory response by increasing the
      secretion of IL-17, an established proinflammatory cytokine in VKH disease.
      Manipulation of IL-9 could represent a novel option for the treatment of VKH
      disease.

PMID- 28761329
TI  - Comparison of different intraocular pressure measurement techniques in normal
      eyes and post small incision lenticule extraction.
AB  - PURPOSE: The purpose of the study was to determine the accuracy of intraocular
      pressure (IOP) measurement after small incision lenticule extraction (SMILE)
      using Goldmann applanation tonometry (GAT) and ocular response analyzer (ORA).
      METHODS: This is a prospective clinical study that was conducted on 30 eyes in
      the interval between February 2016 and September 2016. The age of the patients
      ranged between 19 and 40 years. The patients underwent SMILE surgery using the
      femto laser. IOP was measured preoperatively and 1 month postoperatively by both
      techniques, the GAT and the ORA. RESULTS: GAT recorded lower values than ORA
      values (IOPcc) preoperatively and postoperatively and the difference was
      statistically significant. Both GAT and ORA IOP measurements decreased after
      SMILE. There was no statistically significant correlation between the changes in
      the GAT and ORA readings and the postoperative corneal pachymetry or the
      lenticule thickness. Both corneal hysteresis and corneal resistance factor showed
      significant decline after the procedure, which correlated with the lenticule
      thickness. CONCLUSION: SMILE causes significant reduction in IOP measurement by
      ORA and GAT. Corneal biomechanics decreases following SMILE and this correlates
      with lenticule thickness.

PMID- 28761330
TI  - Epigenetic memory of oxidative stress: does nephrilin exert its protective
      effects via Rac1?
AB  - AIM: Nephrilin peptide, a designed inhibitor of Rictor complex (mTORC2), exerts
      pleiotropic protective effects in metabolic, xenobiotic and traumatic stress
      models. Stress can generate enduring epigenetic changes in gene function. In this
      work we examine the possibility that nephrilin treatment protects against acute
      and enduring global changes in oxidative metabolism, with a focus on the Rictor
      complex-mediated activation of Rac1, a subunit of NADPH oxidase (Nox) via PKCs,
      Prex1 and p66shc. METHODS: Given the wide range of animal models in which
      nephrilin peptide has previously demonstrated effectiveness in vivo, we chose
      three different experimental systems for this investigation: dermal fibroblasts,
      renal proximal tubule epithelial cells (PTECs), and kidney tissue and urine from
      an animal model of burn trauma in which nephrilin was previously shown to prevent
      loss of kidney function. RESULTS: (1) Nephrilin protects dermal fibroblasts from
      loss of viability and collagen synthesis after ultraviolet A (UV-A) or H2O2
      insult. (2) Nephrilin reduces reactive oxygen species (ROS) formation by H2O2
      treated (PTECs) with or without nicotine pretreatment. Using RNA arrays and
      pathway analysis we demonstrate that nicotine and H2O2-treated PTECs specifically
      induced Rac1 gene networks in these cells. (3) Using kidney tissue and urine from
      the burn trauma model we demonstrate significant elevations of [a] 8
      aminoprostane in urine; [b] kidney tissue histone modification and DNA
      methylation; and [c] post-transcriptional phosphorylation events consistent with
      Rac1 activation in kidney tissue. CONCLUSION: Nephrilin protects against
      oxidative stress, possibly by modulating the activation of Rac1.

PMID- 28761331
TI  - Antiglycation, radical scavenging, and semicarbazide-sensitive amine oxidase
      inhibitory activities of acetohydroxamic acid in vitro.
AB  - Advanced glycation endproducts (AGEs) can promote intracellular reactive oxygen
      species production, and the levels of AGEs are highly correlated with
      cardiovascular disease and diabetes complications. Acetohydroxamic acid (acetH)
      is a bacterial urease inhibitor drug used to treat kidney stones and infections
      in the urinary tract, and hydroxyurea (HU) is a drug used for antineoplasm and
      sickle cell diseases. Both acetH and HU are hydroxamic acid derivatives. It was
      found that acetH and HU at 2.5 or 5 mM showed anti-AGE formation by lowering the
      AGEs' fluorescent intensities and Nepsilon-(carboxymethyl)lysine formation in
      bovine serum albumin/galactose models, and both showed better and significant
      differences (P<0.05) compared to the positive control of aminoguanidine.
      Regarding radical scavenging activities, the half-inhibition concentrations
      (IC50) of acetH against alpha,alpha-diphenyl-beta-picrylhydrazyl radical and
      hydroxyl radical were 34.86 and 104.42 MUM, respectively. The IC50 of acetH
      against semicarbazide-sensitive amine oxidase was 10.56 MUM, and acetH showed
      noncompetitive inhibition respective to the substrates (benzylamine). The
      antiglycation, antioxidant, and semicarbazide-sensitive amine oxidase inhibitory
      activities of acetH prove that it has the potential for treating cardiovascular
      disease and diabetes complications and it needs further investigation in animal
      models.

PMID- 28761332
TI  - Using dezocine to prevent etomidate-induced myoclonus: a meta-analysis of
      randomized trials.
AB  - OBJECTIVE: This study was designed to evaluate the efficacy and safety of
      preinjection of dezocine in preventing etomidate-induced myoclonus. METHODS:
      PubMed, Embase, The Cochrane Library, and China National Knowledge Infrastructure
      (CNKI) were searched to collect relevant randomized controlled trials (RCTs) from
      inception to July 2016 on the preinjection of dezocine in preventing etomidate
      induced myoclonus. Two researchers independently screened literature, extracted
      data, and evaluated bias risks in accordance with inclusion and exclusion
      criteria, and then used RevMan 5.2 to perform the meta-analysis. RESULTS: A total
      of six RCTs were included in this study. The meta-analysis showed that 1) the
      preinjection of dezocine can reduce the incidence of etomidate-induced myoclonus
      (relative risk [RR] =0.25, 95% CI [0.13, 0.50], P<0.0001), which is consistent
      with the result of subgroup analysis; 2) the preinjection of dezocine can reduce
      the incidence of mild, moderate, and severe myoclonus; 3) dezocine was not
      related to an increasing incidence of etomidate-induced dizziness and nausea (RR
      =2.83, 95% CI [0.66, 12.08], P=0.6); and 4) dezocine did not reduce heart rates
      after the administration of etomidate (mean difference =1.06, 95% CI [-4.08,
      6.19], P=0.69). CONCLUSION: The preinjection of dezocine has the effect of both
      lowering the incidence of etomidate-induced myoclonus and easing the severity of
      myoclonus, but without increasing dizziness and nausea or affecting the heart
      rate.

PMID- 28761333
TI  - Patient satisfaction with clinical laboratory services at Tikur Anbessa
      Specialized Hospital, Addis Ababa, Ethiopia.
AB  - BACKGROUND: Monitoring patient satisfaction is an important and useful quality
      improvement tool for clinical laboratories in particular and health care
      organizations in general. Thus, this study aimed to assess patient satisfaction
      toward clinical laboratory services at Tikur Anbessa Specialized Hospital (TASH),
      Addis Ababa, Ethiopia. METHODS: A hospital-based cross-sectional study was
      conducted and a convenient sampling technique was applied to recruit study
      participants. A total of 210 patients who had received laboratory services were
      included. A self-administered predesigned, pretested, structured questionnaire
      was used, and data were collected through face-to-face interviews. A 5-point
      Likert scale with 1 and 5 indicating the lowest and highest levels of
      satisfaction, respectively, was used and their weighted average was used to
      categorize the satisfaction level of the patients. Chi square test was used
      (taking P<=0.05 as the statistically significant level) to find out if any
      association existed between the level of satisfaction and different attributes.
      Data were analyzed using SPSS version 20. RESULTS: The overall level of patient
      satisfaction toward clinical laboratory services in this study was 59.7% with a
      response rate of 210 (100%). The Likert scale results of patient satisfaction of
      the laboratory services revealed that the mean rating values ranged from 3.05 (+/
      1.12) to 4.12 (+/-1.08) out of a possible 5. Among the different indicators,
      patients were highly satisfied with the cleanliness of facility (82%),
      maintenance of privacy and confidentiality (83.2%), and the cost of the
      laboratory service (86.5%), while they were dissatisfied with the location of the
      laboratory (56%), latrine accessibility and availability (58.4%), and latrine
      cleanness and comfort (63.8%). CONCLUSION: The whole availability of requested
      tests, availability of place in blood drawing room to put personal things, and
      waiting time for specimen collection were found to have a statistically
      significant association with the overall satisfaction of patients toward clinical
      laboratory services. Therefore, these could be the possible determinants among
      others that account for the dissatisfaction of patients with clinical laboratory
      services.

PMID- 28761334
TI  - Concerns of patients with systemic lupus erythematosus and adherence to therapy -
      a qualitative study.
AB  - PURPOSE: The objectives of this study were 1) to identify the impact of systemic
      lupus erythematosus (SLE) on patients' lives and their reactions to this, as well
      as their main concerns and expectations regarding their disease and treatments;
      and 2) to assess the relationship between these concerns and the adherence to
      treatments, medical visits, and diagnostic tests. PATIENTS AND METHODS:
      Qualitative study, using a convenient sample of SLE patients attending an
      outpatient rheumatology clinic. Semistructured interviews were conducted and
      audiotaped. The full transcripts were analyzed by two different coders using
      content analysis methodology. RESULTS: Fifteen participants were included. SLE
      had a major impact on these patients' lives. Their main concerns were fear of
      disease worsening and becoming dependent on other people, fear of not being able
      to take care of their children or provide for the family, and the possibility of
      transmitting SLE to their offspring. The main reasons for adherence to therapy
      were the wish to avoid manifestations of SLE and trust in the rheumatologist and
      routine. Nonadherence was more common in the beginning of the treatment because
      of the difficulty in accepting a chronic disease that requires lifelong therapy.
      CONCLUSION: Our data underlined the important interplay between adherence to
      medication and the possibility to gather accurate information and proper support
      during the treatment process. Good communication and efficient patient education
      strategies, focused on improving their knowledge about the disease and its
      treatments, may be important to improve adherence to therapy in SLE.

PMID- 28761335
TI  - Primary care patients' expectations regarding medical appointments and their
      experiences during a visit: does age matter?
AB  - INTRODUCTION: There is evidence that meeting patients' expectations toward health
      care correlates with involvement in the treatment they receive. The most
      important patient expectations concern certain types of information: explanation
      of disease and treatment, health promotion, and improvement in quality of life.
      Other demands include proper rapport and emotional support. The aim of this paper
      was to examine different patient groups over the age of 50 years and their
      expectations toward medical visits, evaluated before a visit and after the visit.
      PATIENTS AND METHODS: The study group consisted of 4,921 primary health-care
      patients. The patients received self-administered questionnaires that they filled
      in before and after the appointment with the doctor. Interviews with patients
      were conducted individually by specially trained interviewers. The PRACTA Patient
      Expectations Scale was used to measure the appointment-related expectations of
      the patients. RESULTS: We observed differences related to age in patients'
      expectations before medical visits regarding the following factors: disease
      explanation, treatment explanation, quality of life, rapport, and emotional
      support. The same differences were not observed on health promotion. Evaluation
      of patients' appointment-related experiences after the visit showed that there
      were significant differences between the age-groups regarding all types of
      expectations included in the study. Differences between previsit and postvisit
      measurements were statistically significant in all age-groups. Patients who
      received less than they expected from doctors outnumbered those who received what
      they expected or more in all the groups. CONCLUSION: Patients' expectations
      toward medical visits are conditioned by age. Therefore, doctors should pay more
      attention to requirements related to age in their effort to identify and satisfy
      expectations. This is particularly important in light of the discrepancy between
      previsit expectations and the actual experiences of patients evaluated after the
      visit.

PMID- 28761336
TI  - Association between coping mechanisms and adherence to diabetes-related self-care
      activities: a cross-sectional study.
AB  - In the overall management of the most chronic diseases, including diabetes
      mellitus (DM), adherence to recommended disease-related self-care activities is
      of paramount importance. The diagnosis and presence of a chronic disease may be
      considered a difficult and stressful situation in life, a situation in which
      coping mechanisms are psychological processes developed at a conscious level to
      manage these situations. This study aimed to explore the possible relationship
      between the dominance of one of the four major coping styles and adherence to
      diabetes-related self-care activities (DRSCAs) in the population of patients with
      type 2 DM (T2DM). In a cross-sectional consecutive-case population-based study
      design, 126 patients previously diagnosed with T2DM were enrolled. Coping
      mechanisms were evaluated using the Cope scale inventory, which identifies the
      dominant coping mechanism: problem-, emotion-, social support-, or avoidance
      focused. The quality of DRSCA was evaluated using the summary of diabetes self
      care activities questionnaire, in which a higher score was associated with
      improved adherence. In the study cohort, 45 patients (35.7%) had problem-focused
      coping, 37 (29.4%) had emotion-focused coping, 32 (25.4%) social support-focused
      coping, and 12 (9.5%) had avoidance-focused coping. Patients with emotion-focused
      coping had the highest level (P=0.02) of DRSCA (median 44 points), followed by
      patients with social support-focused coping (median 40 points) and problem
      focused coping (median 36 points), while patients with avoidance-focused coping
      had the lowest SDSCA total score (33 points). The type of dominant coping
      mechanism has a significant impact on the quality of the DRSCA measures
      implemented by the patient to manage their diabetes. Patients with emotion
      focused and social support-focused coping styles tend to have significantly
      increased adherence to DRSCA scores, while patients with other dominant coping
      styles are less interested in managing their disease.

PMID- 28761337
TI  - Size variation and collapse of emphysema holes at inspiration and expiration CT
      scan: evaluation with modified length scale method and image co-registration.
AB  - A novel approach of size-based emphysema clustering has been developed, and the
      size variation and collapse of holes in emphysema clusters are evaluated at
      inspiratory and expiratory computed tomography (CT). Thirty patients were
      visually evaluated for the size-based emphysema clustering technique and a total
      of 72 patients were evaluated for analyzing collapse of the emphysema hole in
      this study. A new approach for the size differentiation of emphysema holes was
      developed using the length scale, Gaussian low-pass filtering, and iteration
      approach. Then, the volumetric CT results of the emphysema patients were analyzed
      using the new method, and deformable registration was carried out between
      inspiratory and expiratory CT. Blind visual evaluations of EI by two readers had
      significant correlations with the classification using the size-based emphysema
      clustering method (r-values of reader 1: 0.186, 0.890, 0.915, and 0.941; reader
      2: 0.540, 0.667, 0.919, and 0.942). The results of collapse of emphysema holes
      using deformable registration were compared with the pulmonary function test
      (PFT) parameters using the Pearson's correlation test. The mean extents of low
      attenuation area (LAA), E1 (<1.5 mm), E2 (<7 mm), E3 (<15 mm), and E4 (>=15 mm)
      were 25.9%, 3.0%, 11.4%, 7.6%, and 3.9%, respectively, at the inspiratory CT, and
      15.3%, 1.4%, 6.9%, 4.3%, and 2.6%, respectively at the expiratory CT. The extents
      of LAA, E2, E3, and E4 were found to be significantly correlated with the PFT
      parameters (r=-0.53, -0.43, -0.48, and -0.25), with forced expiratory volume in 1
      second (FEV1; -0.81, -0.62, -0.75, and -0.40), and with diffusing capacity of the
      lungs for carbon monoxide (cDLco), respectively. The fraction of emphysema that
      shifted to the smaller subgroup showed a significant correlation with FEV1,
      cDLco, forced expiratory flow at 25%-75% of forced vital capacity, and residual
      volume (RV)/total lung capacity (r=0.56, 0.73, 0.40, and -0.58). A detailed
      assessment of the size variation and collapse of emphysema holes may be useful
      for understanding the dynamic collapse of emphysema and its functional relation.

PMID- 28761339
TI  - Systemic delivery of the anticancer agent arenobufagin using polymeric
      nanomicelles.
AB  - Arenobufagin (ABG) is a major active component of toad venom, a traditional
      Chinese medicine used for cancer therapy. However, poor aqueous solubility limits
      its pharmacological studies in vivo due to administration difficulties. In this
      study, we aimed to develop a polymeric nanomicelle (PN) system to enhance the
      solubility of ABG for effective intravenous delivery. ABG-loaded PNs (ABG-PNs)
      were prepared with methoxy poly (ethylene glycol)-block-poly (d,l-lactic-co
      glycolic acid) (mPEG-PLGA) using the solvent-diffusion technique. The obtained
      ABG-PNs were 105 nm in size with a small polydispersity index of 0.08. The
      entrapment efficiency and drug loading were 71.9% and 4.58%, respectively.
      Cellular uptake of ABG-PNs was controlled by specific clathrin-mediated
      endocytosis. In addition, ABG-PNs showed improved drug pharmacokinetics with an
      increased area under the curve value (a 1.73-fold increase) and a decreased
      elimination clearance (37.8% decrease). The nanomicelles showed increased drug
      concentrations in the liver and lung. In contrast, drug concentrations in both
      heart and brain were decreased. Moreover, the nanomicelles enhanced the
      anticancer effect of the pure drug probably via increased cellular uptake of drug
      molecules. In conclusion, the mPEG-PLGA-based nanomicelle system is a
      satisfactory carrier for the systemic delivery of ABG.

PMID- 28761338
TI  - A review of fibrin and fibrin composites for bone tissue engineering.
AB  - Tissue engineering has emerged as a new treatment approach for bone repair and
      regeneration seeking to address limitations associated with current therapies,
      such as autologous bone grafting. While many bone tissue engineering approaches
      have traditionally focused on synthetic materials (such as polymers or
      hydrogels), there has been a lot of excitement surrounding the use of natural
      materials due to their biologically inspired properties. Fibrin is a natural
      scaffold formed following tissue injury that initiates hemostasis and provides
      the initial matrix useful for cell adhesion, migration, proliferation, and
      differentiation. Fibrin has captured the interest of bone tissue engineers due to
      its excellent biocompatibility, controllable biodegradability, and ability to
      deliver cells and biomolecules. Fibrin is particularly appealing because its
      precursors, fibrinogen, and thrombin, which can be derived from the patient's own
      blood, enable the fabrication of completely autologous scaffolds. In this
      article, we highlight the unique properties of fibrin as a scaffolding material
      to treat bone defects. Moreover, we emphasize its role in bone tissue engineering
      nanocomposites where approaches further emulate the natural nanostructured
      features of bone when using fibrin and other nanomaterials. We also review the
      preparation methods of fibrin glue and then discuss a wide range of fibrin
      applications in bone tissue engineering. These include the delivery of cells
      and/or biomolecules to a defect site, distributing cells, and/or growth factors
      throughout other pre-formed scaffolds and enhancing the physical as well as
      biological properties of other biomaterials. Thoughts on the future direction of
      fibrin research for bone tissue engineering are also presented. In the future,
      the development of fibrin precursors as recombinant proteins will solve problems
      associated with using multiple or single-donor fibrin glue, and the combination
      of nanomaterials that allow for the incorporation of biomolecules with fibrin
      will significantly improve the efficacy of fibrin for numerous bone tissue
      engineering applications.

PMID- 28761340
TI  - Physicochemical characterization of drug nanocarriers.
AB  - Pharmaceutical design has enabled important advances in the prevention,
      treatment, and diagnosis of diseases. The use of nanotechnology to optimize the
      delivery of drugs and diagnostic molecules is increasingly receiving attention
      due to the enhanced efficiency provided by these systems. Understanding the
      structures of nanocarriers is crucial in elucidating their physical and chemical
      properties, which greatly influence their behavior in the body at both the
      molecular and systemic levels. This review was conducted to describe the
      principles and characteristics of techniques commonly used to elucidate the
      structures of nanocarriers, with consideration of their size, morphology, surface
      charge, porosity, crystalline arrangement, and phase. These techniques include X
      ray diffraction, small-angle X-ray scattering, dynamic light scattering, zeta
      potential, polarized light microscopy, transmission electron microscopy, scanning
      electron microcopy, and porosimetry. Moreover, we describe some of the commonly
      used nanocarriers (liquid crystals, metal-organic frameworks, silica nanospheres,
      liposomes, solid lipid nanoparticles, and micelles) and the main aspects of their
      structures.

PMID- 28761341
TI  - Sensitive detection of microRNAs based on the conversion of colorimetric assay
      into electrochemical analysis with duplex-specific nuclease-assisted signal
      amplification.
AB  - miRNAs have emerged as new biomarkers for the detection of a wide variety of
      cancers. By employing duplex-specific nuclease for signal amplification and gold
      nanoparticles (AuNPs) as the carriers of detection probes, a novel
      electrochemical assay of miRNAs was performed. The method is based on conversion
      of the well-known colorimetric assay into electrochemical analysis with enhanced
      sensitivity. DNA capture probes immobilized on the electrode surface and
      ferrocene (Fc)-labeled DNA detection probes (denoted "Fc-DNA-Fc") presented in
      the solution induced the assembly of positively charged AuNPs on the electrode
      surface through the electrostatic interaction. As a result, a large number of Fc
      DNA-Fc molecules were attached on the electrode surface, thus amplifying the
      electrochemical signal. When duplex-specific nuclease was added to recycle the
      process of miRNA-initiated digestion of the immobilized DNA probes, Fc-DNA-Fc
      induced assembly of AuNPs on the electrode surface could not occur. This resulted
      in a significant fall in the oxidation current of Fc. The current was found to be
      inversely proportional to the concentration of miRNAs in the range of 0-25 fM,
      and a detection limit of 0.1 fM was achieved. Moreover, this work presents a new
      method for converting colorimetric assays into sensitive electrochemical
      analyses, and thus would be valuable for design of novel chemical/biosensors.

PMID- 28761342
TI  - Transferrin-functionalized nanographene oxide for delivery of platinum complexes
      to enhance cancer-cell selectivity and apoptosis-inducing efficacy.
AB  - Rational design and construction of delivery nanosystems for anticancer metal
      complexes is a crucial strategy to improve solubility under physiological
      conditions and permeability and retention behavior in tumor cells. Therefore, in
      this study, we designed and synthesize a transferrin (Tf)-conjugated nanographene
      oxide (NGO) nanosystem as a cancer-targeted nanocarrier of Pt complexes (Tf
      NGO@Pt). This nanodelivery system exhibited good solubility under physiological
      conditions. Moreover, Tf-NGO@Pt showed higher anticancer efficacy against MCF
      human breast cancer cells than the free Pt complex, and effectively inhibited
      cancer-cell migration and invasion, with involvement of reactive oxygen species
      overproduction. In addition, nanolization also enhanced the penetration ability
      and inhibitory effect of the Pt complex toward MCF7 breast cancer-cell tumor
      spheroids. The enhancement of anticancer efficacy was positively correlated with
      increased cellular uptake and cellular drug retention. This study provides a new
      strategy to facilitate the future application of metal complexes in cancer
      therapy.

PMID- 28761345
TI  - Erratum: Liposomal formulation of a methotrexate lipophilic prodrug: assessment
      in tumor cells and mouse T-cell leukemic lymphoma [Corrigendum].
AB  - [This corrects the article on p. 3735 in vol. 12, PMID: 28553111.].

PMID- 28761343
TI  - Elastic liposomes as novel carriers: recent advances in drug delivery.
AB  - Elastic liposomes (EL) are some of the most versatile deformable vesicular
      carriers that comprise physiologically biocompatible lipids and surfactants for
      the delivery of numerous challenging molecules and have marked advantages over
      other colloidal systems. They have been investigated for a wide range of
      applications in pharmaceutical technology through topical, transdermal, nasal,
      and oral routes for efficient and effective drug delivery. Increased drug
      encapsulation efficiency, enhanced drug permeation and penetration into or across
      the skin, and ultradeformability have led to widespread interest in ELs to
      modulate drug release, permeation, and drug action more efficiently than
      conventional drug-release vehicles. This review provides insights into the
      versatile role that ELs play in the delivery of numerous drugs and biomolecules
      by improving drug release, permeation, and penetration across the skin as well as
      stability. Furthermore, it provides future directions that should ensure the
      widespread use of ELs across all medical fields.

PMID- 28761344
TI  - Synergistic apoptotic effects of apigenin TPGS liposomes and tyroservatide:
      implications for effective treatment of lung cancer.
AB  - To develop an alternative treatment for lung cancer, a combination of two potent
      chemotherapeutic agents - liposomal apigenin and tyroservatide - was developed.
      The therapeutic potential of this combination was investigated using A549 cells.
      Apigenin and tocopherol derivative-containing D-alpha-tocopheryl polyethylene
      glycol 1000 succinate (TPGS) liposomes might improve the delivery of apigenin to
      tumor cells, both in vitro and in vivo. Importantly, compared to either agent
      alone, the combination of apigenin TPGS liposomes and tyroservatide exhibited
      superior cytotoxicity, induced stronger G2 arrest, and suppressed A549 cancer
      cell invasion at a lower dose. The proapoptotic synergistic effects were also
      observed in A549 cells using terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labeling, flow cytometry, and Western blot analysis. More importantly,
      in vivo results showed that the combination of apigenin TPGS liposomes and
      tyroservatide exhibited tumor-growth inhibitory effects in A549 cell-bearing
      mice. In conclusion, our study showed that this combination therapy could serve
      as a promising synergistic therapeutic approach to improve outcomes in patients
      with lung cancer.

PMID- 28761346
TI  - Anxiety sensitivity as a predictor of broad dimensions of psychopathology after
      cognitive behavioral therapy for panic disorder.
AB  - BACKGROUND: Panic disorder (PD) is a common disease and presents with broad
      dimensions of psychopathology. Cognitive behavioral therapy (CBT) is known to
      improve these broad dimensions of psychopathology in addition to PD symptoms.
      However, little is known about the predictors of treatment response in comorbid
      psychiatric symptoms after CBT for PD. Recent studies suggest that anxiety
      sensitivity (AS) may be a key vulnerability for PD. This study aimed to examine
      AS as a predictor of broad dimensions of psychopathology after CBT for PD.
      MATERIALS AND METHODS: In total, 118 patients with PD were treated with
      manualized group CBT. We used multiple regression analysis to examine the
      associations between 3 Anxiety Sensitivity Index (ASI) factors (physical
      concerns, mental incapacitation concerns, and social concerns) at baseline and
      the subscales of the Symptom Checklist-90 Revised (SCL-90-R) at endpoint.
      RESULTS: Low levels of social concerns at baseline predicted low levels on 5 SCL
      90-R subscales after CBT: interpersonal sensitivity, depression, hostility,
      paranoid ideation, and psychosis. High levels of mental incapacitation concerns
      significantly predicted low levels on 3 SCL-90-R subscales after treatment:
      interpersonal sensitivity, hostility, and paranoid ideation. Physical concerns at
      baseline did not predict broad dimensions of psychopathology. CONCLUSION: This
      study suggested that the social concerns and mental incapacitation concerns
      subscales of the ASI at baseline predicted several dimensions of psychopathology
      after CBT for PD. To improve comorbid psychopathology, it may be useful to direct
      more attention to these ASI subscales.

PMID- 28761348
TI  - Depression in blepharospasm: a question of facial feedback?
AB  - Depression is the most important nonmotor symptom in blepharospasm (BL). As
      facial expression influences emotional perception, summarized as the facial
      feedback hypothesis, we investigated if patients report fewer depressive symptoms
      if injections of botulinum neurotoxin (BoNT) include the "grief muscles" of the
      glabellar region, compared to treatment of orbicularis oculi muscles alone.
      Ninety BL patients were included, half of whom had BoNT treatment including the
      frown lines. While treatment pattern did not predict depressive symptoms overall,
      subgroup analysis revealed that in male BL patients, BoNT injections into the
      frown lines were associated with remarkably less depressive symptoms. We
      hypothesize that in BL patients presenting with dystonia of the eyebrow region,
      BoNT therapy should include frown line application whenever justified, to
      optimize nonmotor effects of BoNT denervation.

PMID- 28761349
TI  - Excoriation (skin-picking) disorder: a systematic review of treatment options.
AB  - Although pathological skin-picking has been documented in the medical literature
      since the 19th century, it has only recently been included as a distinct entity
      in psychiatric classification systems. In the Diagnostic and Statistical Manual
      of Mental Disorders, 5th Edition and the proposed International Classification of
      Diseases, Eleventh Revision, excoriation (skin-picking) disorder (ED), also known
      as neurotic excoriation, psychogenic excoriation, or dermatillomania), is
      described as recurrent picking of skin, leading to skin lesions and significant
      distress or functional impairment. ED is listed as one of the obsessive
      compulsive and related disorders, given its overlap with conditions such as
      trichotillomania (hair-pulling disorder). Arguably, its inclusion and delineation
      in the diagnostic nomenclature will lead to increased awareness of the condition,
      more research, and ultimately in treatment advances. This systematic review aims
      to provide readers with an up-to-date view of current treatment options for ED. A
      MEDLINE search of the ED treatment literature was conducted to collate relevant
      articles published between 1996 and 2017. The findings indicate that a number of
      randomized controlled trails on ED have now been published, and that current
      management options include behavioral therapy (habit reversal or acceptance
      enhanced behavior therapy), and medication (selective serotonin reuptake
      inhibitors or N-acetyl cysteine).

PMID- 28761347
TI  - Genetic and epigenetic mechanisms of epilepsy: a review.
AB  - Epilepsy is a common episodic neurological disorder or condition characterized by
      recurrent epileptic seizures, and genetics seems to play a key role in its
      etiology. Early linkage studies have localized multiple loci that may harbor
      susceptibility genes to epilepsy, and mutational analyses have detected a number
      of mutations involved in both ion channel and nonion channel genes in patients
      with idiopathic epilepsy. Genome-wide studies of epilepsy have found copy number
      variants at 2q24.2-q24.3, 7q11.22, 15q11.2-q13.3, and 16p13.11-p13.2, some of
      which disrupt multiple genes, such as NRXN1, AUTS2, NLGN1, CNTNAP2, GRIN2A,
      PRRT2, NIPA2, and BMP5, implicated for neurodevelopmental disorders, including
      intellectual disability and autism. Unfortunately, only a few common genetic
      variants have been associated with epilepsy. Recent exome-sequencing studies have
      found some genetic mutations, most of which are located in nonion channel genes
      such as the LGI1, PRRT2, EFHC1, PRICKLE, RBFOX1, and DEPDC5 and in probands with
      rare forms of familial epilepsy, and some of these genes are involved with the
      neurodevelopment. Since epigenetics plays a role in neuronal function from
      embryogenesis and early brain development to tissue-specific gene expression,
      epigenetic regulation may contribute to the genetic mechanism of neurodevelopment
      through which a gene and the environment interacting with each other affect the
      development of epilepsy. This review focused on the analytic tools used to
      identify epilepsy and then provided a summary of recent linkage and association
      findings, indicating the existence of novel genes on several chromosomes for
      further understanding of the biology of epilepsy.

PMID- 28761350
TI  - Effect of treatment with single total-dose intravenous iron versus daily oral
      iron(III)-hydroxide polymaltose on moderate puerperal iron-deficiency anemia.
AB  - BACKGROUND: Iron-deficiency anemia is the most common nutritional cause of anemia
      in pregnancy and is often responsible for puerperal anemia. Puerperal anemia can
      impair postpartum maternal and neonatal well-being. OBJECTIVE: To determine the
      effect of treatment of moderate puerperal iron-deficiency anemia using a single
      intravenous total-dose iron dextran versus daily single dose oral iron(III)
      hydroxide polymaltose. METHODOLOGY: A randomized controlled study in which
      postpartum women with moderate iron-deficiency anemia were randomized into
      treatment with either a single total-dose intravenous iron dextran or with daily
      single doses of oral iron(III)-hydroxide polymaltose tablets for 6 weeks. Effects
      on hemoglobin concentration using either method were compared at 6 weeks
      postpartum. Analysis was per protocol using SPSS version 17 for windows. P-values
      <=0.05 were considered significant. RESULTS: Two hundred eighty-four women were
      recruited for the study: 142 women received single total dose intravenous
      infusion of iron dextran while 142 received daily oral iron(III)-hydroxide
      polymaltose tablets. Approximately 84.0% (237/282) completed the study and were
      analyzed including 81% (115/142) of those randomized to injectable iron therapy
      compared to 85.9% (122/142) of those randomized to oral treatment. The
      proportions of women who had attained hemoglobin concentration of at least 10
      g/dL by the 6 weeks postpartum visit did not differ significantly between cases
      and controls (95.7% vs 94.3%; P=0.73). Similarly, the mean increases in
      hemoglobin following either therapeutic route were comparable (1.03+/-0.56 g/dL
      for intravenous iron and 0.97+/-0.46 g/dL for the oral group; P=0.42).
      CONCLUSION: Single total-dose intravenous iron for treatment of puerperal iron
      deficiency anemia was as effective as daily single doses of ferric iron tablets.
      For puerperal patients with iron-deficiency anemia in whom compliance with and
      tolerability of oral iron are not certain, a single total-dose intravenous iron
      can be safely offered.

PMID- 28761351
TI  - Alemtuzumab: a review of efficacy and risks in the treatment of relapsing
      remitting multiple sclerosis.
AB  - Alemtuzumab is a selective humanized monoclonal antibody directed against the
      CD52 antigen, and has been found to be a powerful treatment for relapsing
      remitting multiple sclerosis. Alemtuzumab demonstrated high efficacy in several
      clinical studies. The risk of relapse and sustained accumulation of disability
      showed significant reduction in the Phase II CAMMS223 and the Phase III clinical
      trials CARE MS I and CARE MS II. The data presented at the 32nd Congress of the
      European Committee for Treatment and Research in Multiple Sclerosis confirmed
      these results. After completion of a 1-year treatment cycle, alemtuzumab showed a
      sustained effect. Although the efficacy of alemtuzumab has been widely proven,
      several severe adverse effects have been reported with its use. Infusion
      associated reactions, increased risk of infections, and secondary autoimmunity
      have been associated with alemtuzumab. Autoimmune disease - mainly of the thyroid
      - has been reported. Immune thrombocytopenic purpura and autoimmune nephropathies
      have been observed less frequently. These adverse effects, given the short period
      of alemtuzumab marketing for relapsing remitting multiple sclerosis, require
      strict monitoring.

PMID- 28761352
TI  - Use of angiotensin-converting enzyme inhibitors and freedom from amputation after
      lower extremity revascularization.
AB  - OBJECTIVE: Angiotensin-converting enzyme inhibitors (ACEIs) have not been well
      evaluated in conjunction with lower extremity revascularization (LER). This study
      evaluated freedom from amputation in patients who underwent either an open (OPEN)
      or endovascular (ENDO) revascularization with and without utilization of an ACEI.
      MATERIALS AND METHODS: Patients who underwent LER were identified from 2007-2008
      Medicare Provider Analysis and Review files. Demographics, comorbidities, and
      disease severity were obtained. Post-procedural use of an ACEI was confirmed
      using combining them with National Drug Codes and Part D Files. Outcomes were
      analyzed using chi-square analysis, Kaplan-Meier test, and Cox regression.
      RESULTS: We identified 22,954 patients who underwent LER: 8,128 (35.4%) patients
      with claudication, 3,056 (13.3%) with rest pain, and 11,770 (51.3%) with
      ulceration or gangrene. More patients underwent ENDO (14,353) than OPEN (8,601)
      revascularization and 38% of the cohort was taking an ACEI. Overall, ACEI
      utilization compared to patients not taking ACEI was not associated with lower
      amputation rates at 30 days (13.5% vs. 12.6%), 90 days (17.7% vs. 17.1%), or 1
      year (23.9% vs. 22.8%) (P>0.05 for all). After adjustment for comorbidities, ACEI
      utilization was associated with higher amputation rates for patients with rest
      pain (hazard ratio: 1.4; 95% confidence interval: 1.1-1.8). CONCLUSION: ACEI
      utilization was not associated with overall improved rates of amputation-free
      survival or overall survival in the vascular surgery population. However, an
      important finding of this study was that patients presenting with a diagnosis of
      rest pain and taking an ACEI who underwent a LER had statistically higher
      amputation rates and a lower amputation-free survival at 1 year. Further analysis
      is needed to delineate best medical management for patients with critical limb
      ischemia and taking ACEI who undergo vascular revascularization.

PMID- 28761353
TI  - Hypertension and blood pressure variability management practices among physicians
      in Singapore.
AB  - PURPOSE: There are limited data on blood pressure variability (BPV) in Singapore.
      The absence of updated local guidelines might contribute to variations in
      diagnosis, treatment and control of hypertension and BPV between physicians. This
      study evaluated BPV awareness, hypertension management and associated training
      needs in physicians from Singapore. MATERIALS AND METHODS: Physicians from
      Singapore were surveyed between September 8, 2016, and October 5, 2016. Those
      included were in public or private practice for >=3 years, cared directly for
      patients >=70% of the time and treated >=30 patients for hypertension each month.
      The questionnaire covered 6 main categories: general blood pressure (BP)
      management, BPV awareness/diagnosis, home BP monitoring (HBPM), ambulatory BP
      monitoring (ABPM), BPV management and associated training needs. RESULTS:
      Responses from 60 physicians (30 general practitioners [GPs], 20 cardiologists,
      10 nephrologists) were analyzed (77% male, 85% aged 31-60 years, mean 22 years of
      practice). Approximately 63% of physicians considered white-coat hypertension as
      part of BPV. The most common diagnostic tool was HBPM (overall 77%, GPs 63%,
      cardiologists 65%, nephrologists 70%), but ABPM was rated as the tool most valued
      by physicians (80% overall), especially specialists (97%). Withdrawn Singapore
      guidelines were still being used by 73% of GPs. Approximately 48% of physicians
      surveyed did not adhere to the BP cutoff recommended by most guidelines for
      diagnosing hypertension using HBPM (>135/85 mmHg). Hypertension treatment
      practices also varied from available guideline recommendations, although
      physicians did tend to use a lower BP target for patients with diabetes or kidney
      disease. There were a number of challenges to estimating BPV, the most common of
      which was patient refusal of ABPM/HBPM. The majority of physicians (82%) had no
      training on BPV, but stated that this would be useful. CONCLUSION: There appear
      to be gaps in knowledge and guideline adherence relating to the assessment and
      management of BPV among physicians in Singapore.

PMID- 28761354
TI  - PD-1 blockade restores impaired function of ex vivo expanded CD8+ T cells and
      enhances apoptosis in mismatch repair deficient EpCAM+PD-L1+ cancer cells.
AB  - BACKGROUND: Adoptive T cell therapy has been proven to be a promising modality
      for the treatment of cancer patients in recent years. However, the increased
      expression of inhibitory receptors could negatively regulate the function and
      persistence of transferred T cells which mediates T cell anergy, exhaustion, and
      tumor regression. In this study, we investigated increased cytotoxic activity
      after the blockade of PD-1 for effective immunotherapy. METHODS: The cytotoxic
      function of expanded CD8+ CTLs and interactions with tumor cells investigated
      after blocking of PD-1. Ex vivo expanded CD8+ CTLs were co-cultured with mismatch
      repair (MMR) stable or deficient (high microsatellite instability [MSI-H]) EpCAM+
      tumor cells. The levels of IFN-gamma and GrB were detected by enzyme-linked
      immunosorbent spot assay. Flow cytometry and confocal microscopy were used to
      assess CD107a mobilization, cytosolic uptake, and cell migration. RESULTS: A
      dramatic increase in PD-1 expression on the surface of CD8+ CTLs during ex vivo
      expansion was observed. PD-1 level was downregulated by approximately 40% after
      incubation of the CD8+ CTLs with monoclonal antibody which enhanced the secretion
      of IFN-gamma, GrB, and CD107a. Additionally, PD-1 blockade enhanced cell
      migration and cytosolic exchange between CD8+ CTLs and MMR deficient (MSI-H)
      EpCAM+PD-L1+ tumor cells. CONCLUSION: The blockade of PD-1 enhanced the cytotoxic
      efficacy of CD8+ CTLs toward MMR deficient tumor cells. In conclusion, we propose
      that blocking of PD-1 during the expansion of CD8+ CTLs may improve the clinical
      efficacy of cell-based adoptive immunotherapy.

PMID- 28761355
TI  - Ergosterol peroxide inhibits ovarian cancer cell growth through multiple
      pathways.
AB  - Ergosterol peroxide (EP), a sterol derived from medicinal mushrooms, has been
      reported to exert antitumor activity in several tumor types. However, the role of
      EP toward ovarian cancer cells has not been investigated. In this study, we
      analyzed the cytotoxicity of EP in various cell lines representing high-grade
      serous ovarian cancer and low-grade serous ovarian cancer, respectively. Although
      EP showed no significant inhibition of the viability of normal ovarian surface
      epithelial cells, it impaired the proliferation and invasion capacities of tumor
      cells in a dose-dependent manner. We further figured out key modulators involved
      in its antitumor effects by quantitative reverse transcription polymerase chain
      reaction, ELISA, and Western blot. The nuclear beta-catenin was down-regulated
      upon EP treatment, subsequently reducing the Cyclin D1 and c-Myc expression
      levels. Meanwhile, the protein level of protein tyrosine phosphatase SHP2 was up
      regulated in EP treated cells, whereas Src kinase activity was inhibited. Both
      activation of SHP2 phosphatase and inhibition of Src kinase decreased the
      phosphorylation level of transducer and activator of STAT3 protein, which was
      implicated in oncogenesis. On the other hand, EP remarkably inhibited the
      expression and secretion of VEGF-C, implying its involvement in counteracting
      tumor angiogenesis. Moreover, EP treatment showed comparable cytotoxic effect
      with beta-catenin knock-down or STAT3 inhibition. Taken together, our results
      demonstrated that EP showed antitumor effects toward ovarian cancer cells through
      both beta-catenin and STAT3 signaling pathways, making it a promising candidate
      for drug development.

PMID- 28761356
TI  - Association between polymorphisms in DNA repair gene XRCC1 and non-melanoma skin
      cancer risk: a meta-analysis.
AB  - OBJECTIVE: Non-melanoma skin cancer (NMSC) is the most common malignancy with
      annually rising incidence. The aim of this study was to estimate the association
      between three coding polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) of the
      DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) and NMSC
      susceptibility. METHODS: Online databases were searched to retrieve case-control
      studies published between January 2000 and November 2016. Pooled odds ratio (OR)
      and 95% confidence interval (CI) were employed to assess the strength of
      association. Overall, 10 relevant studies were finally included for analysis,
      including 3,143 NMSC patients and 3,540 controls. For each polymorphism of XRCC1
      gene, there were 3,050 cases and 3,463 controls for Arg399Gln, 914 cases and
      1,182 controls for Arg194Trp, and 279 cases and 413 controls for Arg280His.
      RESULTS: Our results showed that these three polymorphisms in the XRCC1 coding
      region were not associated with increased risk of NMSC in the total studied
      population. However, subgroup analysis by ethnicities demonstrated that Gln/Arg
      genotype of Arg399Gln polymorphism was associated with increased risk of NMSC
      under the heterogeneous model in Asian populations (Gln/Arg vs Arg/Arg: OR =1.39,
      95% CI =1.04-1.87, P=0.03); subgroup analysis by tumor types showed that Trp/Trp
      genotype of Arg194Trp was positively associated with decreased cancer risk in
      squamous-cell skin cancer (SCC) type under the homogeneous model (Trp/Trp vs
      Arg/Arg: OR =0.38, 95% CI =0.16-0.92, P=0.03). CONCLUSION: Our results suggested
      that Arg399Gln variant of XRCC1 gene might be a risk factor for NMSC in Asian
      populations, and Arg194Trp variant of XRCC1 gene might be a protective factor for
      patients with SCC. In addition, future case-control studies are still needed to
      further evaluate the effect of XRCC1 polymorphisms in NMSC risk.

PMID- 28761357
TI  - Interleukin-35 as a predictor of prostate cancer in patients undergoing initial
      prostate biopsy.
AB  - BACKGROUND: Interleukin (IL)-35 is a novel inhibitory cytokine and has recently
      been implicated in tumor immunity. However, the role of IL-35 in prostate cancer
      (PCa) has not been elucidated. OBJECTIVE: To evaluate the role of plasma IL-35 in
      the diagnosis and prognosis of PCa in Chinese patients undergoing initial
      prostate biopsy. MATERIALS AND METHODS: Using ELISA, plasma IL-35 levels were
      measured in 180 patients, who underwent a prostate biopsy. The clinical
      correlation of IL-35 with clinicopathological parameters was also evaluated.
      Univariate and multivariate logistic regression and receiver operating
      characteristic (ROC) curve analysis were performed to establish the role of IL-35
      as a clinical biomarker. RESULTS: Seventy-five (41.6%) of patients were
      histopathologically confirmed to have PCa. Plasma IL-35 levels were significantly
      higher in PCa patients (134.48+/-78.48 pg/mL) compared to non-PCa patients
      (67.22+/-24.08 pg/mL). ROC analysis showed that IL-35 was an independent
      predictor of PCa. Furthermore, IL-35 was found to be a significantly independent
      predictor of PCa in a group of patients with prostate-specific antigen levels
      between 4 and 10 ng/mL; was also able to predict advanced PCa from localized PCa
      and bone metastasis positive PCa from negative PCa. CONCLUSION: Our data suggest
      for the first time that plasma IL-35 levels are correlated with PCa and is the
      independent predictor of PCa progression and metastasis. Thus, IL-35 could be
      utilized as a potential biomarker for diagnosis and prognosis of PCa, could also
      aid in decision making and predict the stage of the disease.

PMID- 28761358
TI  - An evaluation of the clinical diagnostic value of contrast-enhanced ultrasound
      combined with contrast-enhanced computed tomography in space-occupying lesions of
      the kidney.
AB  - BACKGROUND: There are a variety of space-occupying lesions of the kidney, and the
      benign lesions may be difficult to differentiate from the malignant ones.
      Therefore, an accurate judgment of the benign and malignant nature of the space
      occupying lesions of the kidney is of high importance for the treatment and
      prognosis of these patients. OBJECTIVE: To evaluate the diagnostic value of
      contrast-enhanced ultrasound (CEUS) combined with contrast-enhanced computed
      tomography (CECT) in space-occupying lesions of the kidney. DATA AND METHODS:
      Three hundred and sixty-seven patients with space-occupying lesions of the kidney
      (378 lesions) were examined by CEUS and CECT, respectively, then, a combined
      diagnosis was made after the combination of CEUS and CECT by a multidisciplinary
      team. The diagnoses from the three methods were compared. The pathological
      results were taken as the gold standard. The sensitivity, specificity, positive
      and negative predictive values and area under the receiver operating
      characteristic (ROC) curve were calculated for the three methods. Thus, the
      diagnostic value of the three methods was assessed. RESULTS: Of the 378 lesions
      examined, there were 301 malignant lesions and 77 benign lesions. The combined
      examination revealed 303 malignant lesions, with 9 benign lesions mistakenly
      diagnosed as malignant ones; thus, the misdiagnosis rate was 11.7%. By using the
      combined examination, 75 benign lesions were diagnosed, with the missed diagnosis
      of 7 malignant lesions, so the missed diagnosis rate was 2.3%. The sensitivity,
      specificity, positive and negative predictive values and area under the ROC curve
      with the combined examination of CEUS and CECT were 97.67% (0.950-0.989), 88.31%
      (0.785-0.942), 97.03% (0.942-0.985), 90.67% (0.811-0.958) and 0.930 (0.887
      0.973), respectively. As compared with either CEUS or CECT alone, the difference
      in these indicators was of statistical significance (P<0.05). The combined
      examination greatly improved the sensitivity, specificity and accuracy of the
      diagnosis of the space-occupying lesions of the kidney. CONCLUSION: CEUS and CECT
      each have advantages and disadvantages in the diagnosis of the space-occupying
      lesions of the kidney. The two techniques can be used in combination to
      compensate for the respective defects. More salient benefits can be reaped from
      the combined examination than from either technique used alone.

PMID- 28761360
TI  - Analysis of clinical characteristics and efficacy of chronic myeloid leukemia
      onset with extreme thrombocytosis in the era of tyrosine kinase inhibitors.
AB  - The aim of this study was to investigate the clinical characteristics and
      efficacy of chronic myeloid leukemia (CML) onset with extreme thrombocytosis. A
      total of 121 newly diagnosed and untreated CML patients in chronic phase with
      complete clinical information from the First Hospital of Jilin University, from
      January 2010 to December 2014 were retrospectively recruited. Based on the
      platelet (PLT) count, 22 patients were assigned into CML with thrombocytosis (CML
      T) group (PLT >1,000*109/L) and 65 patients were classified into CML without
      extreme thrombocytosis (CML-N) group (PLT <=1,000*109/L). Fifty-four point five
      percent of patients in the CML-T group were female, which was higher than that in
      the CML-N group (27.7%) (P=0.022). Except for gender, there was no significant
      difference for clinical information of patients between the two groups. For Sokal
      and Hasford scoring systems, the percentage of patients at high risk in the CML-T
      group were higher than those in the CML-N group, 95.5% vs 52.3% (P=0.000) and
      68.2% vs 41.5% (P=0.031), respectively; however, there was no significant
      difference for European Treatment and Outcome Study (EUTOS) score system between
      the two groups (P=0.213). In terms of major molecular response (MMR) rate, the
      percent of patients with MMR in CML-T group was lower than that in CML-N group at
      36 months after tyrosine kinase inhibitor therapy (P=0.037). Up until December
      2016, the median of event-free survival was 21 months in the CML-T group,
      however, that was not reached in the CML-N group (P=0.027). The majority of CML
      patients with extreme thrombocytosis were females, and compared to patients in
      the CML-N group, the percentage of high risk patients based on the Sokal and
      Hasford scoring systems was higher in the CML-T group, and the median event-free
      survival of patients was shorter.

PMID- 28761359
TI  - Nuclear DDX3 expression predicts poor outcome in colorectal and breast cancer.
AB  - PURPOSE: DEAD box protein 3 (DDX3) is an RNA helicase with oncogenic properties
      that shuttles between the cytoplasm and nucleus. The majority of DDX3 is found in
      the cytoplasm, but a subset of tumors has distinct nuclear DDX3 localization of
      yet unknown biological significance. This study aimed to evaluate the
      significance of and mechanisms behind nuclear DDX3 expression in colorectal and
      breast cancer. METHODS: Expression of nuclear DDX3 and the nuclear exporter
      chromosome region maintenance 1 (CRM1) was evaluated by immunohistochemistry in
      304 colorectal and 292 breast cancer patient samples. Correlations between the
      subcellular localization of DDX3 and CRM1 and the difference in overall survival
      between patients with and without nuclear DDX3 were studied. In addition, DDX3
      mutants were created for in vitro evaluation of the mechanism behind nuclear
      retention of DDX3. RESULTS: DDX3 was present in the nucleus of 35% of colorectal
      and 48% of breast cancer patient samples and was particularly strong in the
      nucleolus. Nuclear DDX3 correlated with worse overall survival in both colorectal
      (hazard ratio [HR] 2.34, P<0.001) and breast cancer (HR 2.39, P=0.004) patients.
      Colorectal cancers with nuclear DDX3 expression more often had cytoplasmic
      expression of the nuclear exporter CRM1 (relative risk 1.67, P=0.04). In vitro
      analysis of DDX3 deletion mutants demonstrated that CRM1-mediated export was most
      dependent on the N-terminal nuclear export signal. CONCLUSION: Overall, we
      conclude that nuclear DDX3 is partially CRM1-mediated and predicts worse survival
      in colorectal and breast cancer patients, putting it forward as a target for
      therapeutic intervention with DDX3 inhibitors under development in these cancer
      types.

PMID- 28761361
TI  - Circ-104916 is downregulated in gastric cancer and suppresses migration and
      invasion of gastric cancer cells.
AB  - Circular RNAs are a large class of noncoding RNA that have shown huge
      capabilities as gene regulators. Recent evidence suggest that circular RNAs are
      associated with many diseases, especially cancer. However, little attention has
      been focused on the expression and function of circular RNA in gastric cancer
      (GC). In this study, we demonstrate that the expression of circ-104916 is
      downregulated in GC tissues and cell lines. A lower expression of circ-104916
      appeared in deeper invasion depth, higher tumor stage and more frequent lymphatic
      metastasis patients. Overexpression of circ-104916 effectively inhibited the
      proliferation, migration and invasion abilities of GC cells in vitro. Western
      blot showed that circ-104916 overexpression upregulated E-cadherin and
      downregulated N-cadherin, Vimentin and Slug, indicating that circ-104916 was
      involved in the epithelial-mesenchymal transition process. Our results revealed
      that circ-104916 might be a novel potential tumor suppressor and biomarker of GC.

PMID- 28761363
TI  - The cost utility and budget impact of adjuvant racecadotril for acute diarrhea in
      children in Thailand.
AB  - OBJECTIVE: To evaluate the cost utility and the budget impact of adjuvant
      racecadotril for the treatment of acute diarrhea in children in Thailand.
      METHODS: A cost utility model has been adapted to the context of Thailand to
      evaluate racecadotril plus oral rehydration solution (R+ORS) versus oral
      rehydration solution (ORS) alone for acute diarrhea in children <5 years old. The
      decision tree Excel model evaluates the costs and effects (quality-adjusted life
      years) over a 6-day time horizon from a public health care payer's perspective in
      Thailand. Deterministic sensitivity analysis and budget impact analysis have been
      undertaken. RESULTS: According to the cost utility model, the intervention
      (R+ORS) is less costly and more effective than the comparator (ORS) for the base
      case with a dominant incremental cost-effectiveness ratio of -2,481,390? for the
      intervention. According to the budget impact analysis (assuming an increase of 5%
      market share for R+ORS over 5 years), the year-on-year reduction for diarrhea as
      a percentage of the total health care expenditure is -0.0027%, resulting in
      potential net cost savings of -35,632,482? over 5 years. CONCLUSION: Subject to
      the assumptions and limitations of the models, adjuvant racecadotril versus ORS
      alone is potentially cost-effective for children in Thailand and uptake could
      translate into savings for the Thailand public health care system.

PMID- 28761362
TI  - Targeted TPX2 increases chromosome missegregation and suppresses tumor cell
      growth in human prostate cancer.
AB  - Prostate cancer is a complex disease that can be relatively harmless or extremely
      aggressive. Although androgen-deprivation therapy is a commonly used treatment
      for men with prostate cancer, the adverse effects can be detrimental to patient
      health and quality of life. Therefore, identifying new target genes for tumor
      growth will enable the development of novel therapeutic intervention. TPX2 plays
      a critical role in chromosome segregation machinery during mitosis. Low rates of
      chromosome missegregation can promote tumor development, whereas higher levels
      might promote cell death and suppress tumorigenesis. Hence, the strategy of
      promoting cell death by inducing massive chromosome missegregation has been a
      therapeutic application for selectively eliminating highly proliferating tumor
      cells. RNAi was used for TPX2 protein expression knockdown, and a clonogenic
      assay, immunostaining, double thymidine block, image-cytometry analysis, and
      tumor spheroid assay were used to analyze the role of TPX2 in tumor cell growth,
      cell cycle progression, multinuclearity, ploidy, and tumorigenicity,
      respectively; finally, Western blotting was used to analyze anticancer mechanisms
      in TPX2 targeting. We demonstrated that targeting TPX2 reduced cell cycle
      regulators and chromosome segregation genes, resulting in increased cell
      micronucleation. Moreover, TPX2 depletion led to prostate cancer cell growth
      inhibition, increased apoptosis, and reduced tumorigenesis. These results
      confirmed the therapeutic potential of targeting TPX2 in prostate cancer
      treatment. Moreover, we found that TPX2 silencing led to deregulation of CDK1,
      cyclin B, securin, separase, and aurora A proteins; by contrast, p21 mRNA was
      upregulated. We also determined the molecular mechanisms for TPX2 targeting in
      prostate cancer cells. In conclusion, our study illustrates the power of TPX2 as
      a potential novel target gene for prostate cancer treatment.

PMID- 28761364
TI  - Effect of astaxanthin on cutaneous wound healing.
AB  - Wound healing consists of a complex series of convoluted processes which involve
      renewal of the skin after injury. ROS are involved in all phases of wound
      healing. A balance between oxidative and antioxidative forces is necessary for a
      favorable healing outcome. Astaxanthin, a member of the xanthophyll group, is
      considered a powerful antioxidant. In this study, we investigated the effect of
      topical astaxanthin on cutaneous wound healing. Full-thickness dermal wounds were
      created in 36 healthy female mice, which were divided into a control group and a
      group receiving 78.9 uM topical astaxanthin treatment twice daily for 15 days.
      Astaxanthin-treated wounds showed noticeable contraction by day 3 of treatment
      and complete wound closure by day 9, whereas the wounds of control mice revealed
      only partial epithelialization and still carried scabs. Wound healing biological
      markers including Col1A1 and bFGF were significantly increased in the astaxanthin
      treated group since day 1. Interestingly, the oxidative stress marker iNOS showed
      a significantly lower expression in the study. The results indicate that
      astaxanthin is an effective compound for accelerating wound healing.

PMID- 28761365
TI  - Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study
      over a 12-week period.
AB  - BACKGROUND: Hyaluronan (HA) has critical moisturizing property and high water
      retention capacity especially for human skin. This study aimed to evaluate the
      effect of oral intake of HA. METHODS: The mean molecular weight (MW) of HA is 2 k
      and 300 k. Sixty Japanese male and female subjects aged 22-59 years who presented
      with crow's feet wrinkles were randomly assigned to the HA 2 k or HA 300 k at 120
      mg/day or the placebo group. The subjects were administered HA at a rate of 120
      mg/day or a placebo for 12 weeks. The skin wrinkles were evaluated by image
      analysis of skin wrinkle replicas, and their skin condition was evaluated using a
      questionnaire survey. RESULTS: During the study period, the HA groups showed
      better level of the whole sulcus volume ratio, wrinkle area ratio, and wrinkle
      volume ratio than the placebo group. After 8 weeks of ingestion, the HA 300 k
      group showed significantly diminished wrinkles compared with the placebo group.
      Skin luster and suppleness significantly improved after 12 weeks in all groups
      compared with the baseline. CONCLUSION: The results suggest that oral HA (both HA
      2 k and HA 300 k) inhibits skin wrinkles and improves skin condition.

PMID- 28761368
TI  - Ultrasound-guided bilateral superficial cervical plexus block is more effective
      than landmark technique for reducing pain from thyroidectomy.
AB  - PURPOSE: Thyroidectomy causes postoperative pain and patient discomfort.
      Bilateral superficial cervical plexus block is a regional anesthesia technique
      that can provide analgesia during and after surgery. This study aims to compare
      the effectiveness of ultrasound (US)-guided versus landmark (LM) technique for
      bilateral superficial cervical plexus block in thyroidectomy. PATIENTS AND
      METHODS: Thirty-six patients undergoing thyroidectomy were divided into two
      groups randomly (n=18); either US-guided (US group) or LM technique (LM group)
      for bilateral superficial cervical plexus block. Patient-controlled analgesia was
      used to control postoperative pain. Intraoperative opioid rescue, postoperative
      visual analog scale (VAS) score and opioid consumption were measured. RESULTS:
      The number of patients who required intraoperative opioid rescue was
      significantly lower in the US group (p<=0.05). There was no significant
      difference in postoperative VAS score at 3 hours (p>0.05), but postoperative VAS
      score at 6 and 24 hours was significantly lower in the US group (p<=0.05). Twenty
      four hour postoperative opioid consumption was significantly lower in the US
      group (p<=0.05). CONCLUSION: Ultrasound-guided bilateral superficial cervical
      plexus block is more effective in reducing pain both intra- and postoperatively
      compared with landmark technique in patients undergoing thyroidectomy.

PMID- 28761366
TI  - Colorectal endoscopic submucosal dissection: patient selection and special
      considerations.
AB  - Endoscopic submucosal dissection (ESD) enables en bloc resection of large complex
      colorectal superficial neoplastic lesions, resulting in very low rates of local
      recurrence, high-quality pathologic specimens for accurate histopathologic
      diagnosis and potentially curative treatment of early adenocarcinoma without
      resorting to major surgical resection. The safety and efficacy of the technique,
      which was pioneered in the upper gastrointestinal tract, has been established by
      the consistently impressive outcomes from expert centers in Japan and some other
      eastern countries. However, ESD is challenging to perform in the colorectum and
      there is a significant risk of complications, particularly in the early stages of
      the learning curve. Early studies from western centers raised concerns about the
      high complication rates, and the impressive results from Japanese centers were
      not replicated. As a result, many western endoscopists are skeptical about the
      role of ESD and few centers have incorporated the technique into their practice.
      Nevertheless, although the distribution of expertise, referral centers and modes
      of practice may differ in Japan and western countries, ESD has an important role
      and can be safely and effectively incorporated into western practice. Key to
      achieving this is meticulous lesion assessment and selection, appropriate
      referral to centers with the necessary expertise and experience and application
      of the appropriate technique individualized to the patient. This review discusses
      the advantages, risks and benefits of ESD to treat colorectal lesions and the
      importance of preprocedure lesion assessment and in vivo diagnosis and outlines a
      pragmatic rationale for appropriate lesion selection as well as the patient,
      technical and institutional factors that should be considered.

PMID- 28761367
TI  - Protein losing enteropathy: comprehensive review of the mechanistic association
      with clinical and subclinical disease states.
AB  - Protein losing enteropathy (PLE) has been associated with more than 60 different
      conditions, including nearly all gastrointestinal diseases (Crohn's disease,
      celiac, Whipple's, intestinal infections, and so on) and a large number of non
      gut conditions (cardiac and liver disease, lupus, sarcoidosis, and so on). This
      review presents the first attempt to quantitatively understand the magnitude of
      the PLE in relation to the associated pathology for three different disease
      categories: 1) increased lymphatic pressure (e.g., lymphangiectasis); 2) diseases
      with mucosal erosions (e.g., Crohn's disease); and 3) diseases without mucosal
      erosions (e.g., celiac disease). The PLE with lymphangiectasis results from
      rupture of the mucosal lymphatics, with retrograde drainage of systemic lymph
      into the intestinal lumen with the resultant loss of CD4 T cells, which is
      diagnostic. Mucosal erosion PLE results from macroscopic breakdown of the mucosal
      barrier, with the epithelial capillaries becoming the rate-limiting factor in
      albumin loss. The equation derived to describe the relationship between the
      reduction in serum albumin (CP) and PLE indicates that gastrointestinal albumin
      clearance must increase by at least 17 times normal to reduce the CP by half. The
      strengths and limitations of the two quantitative measures of PLE (51Cr-albumin
      or alpha1-antitrypsin [alphaAT] clearance) are reviewed. alphaAT provides a
      simple quantitative diagnostic test that is probably underused clinically. The
      strong, unexplained correlation between minor decreases in CP and subsequent
      mortality in seemingly healthy individuals raises the question of whether
      subclinical PLE could account for the decreased CP and, if so, could the
      mechanism responsible for PLE play a role in the increased mortality? A large
      scale study correlating alphaAT clearance with serum albumin concentrations will
      be required in order to determine the role of PLE in the regulation of the serum
      albumin concentration of seemingly healthy subjects.

PMID- 28761370
TI  - Phenytoin and carbamazepine in trigeminal neuralgia: marketing-based versus
      evidence-based treatment.

PMID- 28761369
TI  - Capsaicin 8% patch treatment for amputation stump and phantom limb pain: a
      clinical and functional MRI study.
AB  - PURPOSE: The aim of this study was to measure the efficacy of a single 60 min
      application of capsaicin 8% patch in reducing chronic amputation stump and
      phantom limb pain, associated hypersensitivity with quantitative sensory testing,
      and changes in brain cortical maps using functional MRI (fMRI) scans. METHODS: A
      capsaicin 8% patch (Qutenza) treatment study was conducted on 14 patients with
      single limb amputation, who reported pain intensity on the Numerical Pain Rating
      Scale >=4/10 for chronic stump or phantom limb pain. Pain assessments,
      quantitative sensory testing, and fMRI (for the lip pursing task) were performed
      at baseline and 4 weeks after application of capsaicin 8% patch to the amputation
      stump. The shift into the hand representation area of the cerebral cortex with
      the lip pursing task has been correlated with phantom limb pain intensity in
      previous studies, and was the fMRI clinical model for cortical plasticity used in
      this study. RESULTS: The mean reduction in spontaneous amputation stump pain,
      phantom limb pain, and evoked stump pain were -1.007 (p=0.028), -1.414 (p=0.018),
      and -2.029 (p=0.007), respectively. The areas of brush allodynia and pinprick
      hypersensitivity in the amputation stump showed marked decreases: -165 cm2, -80%
      (p=0.001) and -132 cm2, -72% (p=0.001), respectively. fMRI analyses provided
      objective evidence of the restoration of the brain map, that is, reversal of the
      shift into the hand representation of the cerebral cortex with the lip pursing
      task (p<0.05). CONCLUSION: The results show that capsaicin 8% patch treatment
      leads to significant reduction in chronic pain and, particularly, in the area of
      stump hypersensitivity, which may enable patients to wear prostheses, thereby
      improving mobility and rehabilitation. Phantom limb pain ("central" pain) and
      associated brain plasticity may be modulated by peripheral inputs, as they can be
      ameliorated by the peripherally restricted effect of the capsaicin 8% patch.

PMID- 28761371
TI  - Dissatisfaction with own body makes patients with eating disorders more sensitive
      to pain.
AB  - Body image represents a multidimensional concept including body image evaluation
      and perception of body appearance. Disturbances of body image perception are
      considered to be one of the central aspects of anorexia nervosa and bulimia
      nervosa. There is growing evidence that body image distortion can be associated
      with changes in pain perception. The aim of our study was to examine the
      associations between body image perception, body dissatisfaction, and nociception
      in women with eating disorders and age-matched healthy control women. We measured
      body dissatisfaction and pain sensitivity in 61 patients with Diagnostic and
      Statistical Manual of Mental Disorders-Fourth Edition diagnoses of eating
      disorders (31 anorexia nervosa and 30 bulimia nervosa) and in 30 healthy women.
      Thermal pain threshold latencies were evaluated using an analgesia meter and body
      image perception and body dissatisfaction were assessed using Anamorphic Micro
      software (digital pictures of their own body distorted into larger-body and
      thinner-body images). Patients with eating disorders overestimated their body
      size in comparison with healthy controls, but the two groups did not differ in
      body dissatisfaction. In anorexia and bulimia patient groups, body
      dissatisfaction (calculated in pixels as desired size/true image size) correlated
      with pain threshold latencies (r=0.55, p=0.001), while between body image
      perception (determined as estimation size/true image size) and pain threshold, no
      correlation was found. Thus, we demonstrated that in patients with eating
      disorders, pain perception is significantly associated with emotional contrary to
      sensory (visual) processing of one's own body image. The more the patients
      desired to be thin, the more pain-sensitive they were. Our findings based on some
      shared mechanisms of body dissatisfaction and pain perception support the
      significance of negative emotions specific for eating disorders and contribute to
      better understanding of the psychosomatic characteristics of this spectrum of
      illnesses.

PMID- 28761372
TI  - Application of advanced biomechanical methods in studying low back pain - recent
      development in estimation of lower back loads and large-array surface
      electromyography and findings.
AB  - Low back pain (LBP) is a major public health problem and the leading disabling
      musculoskeletal disorder globally. A number of biomechanical methods using
      kinematic, kinetic and/or neuromuscular approaches have been used to study LBP.
      In this narrative review, we report recent developments in two biomechanical
      methods: estimation of lower back loads and large-array surface electromyography
      (LA-SEMG) and the findings associated with LBP. The ability to estimate lower
      back loads is very important for the prevention and the management of work
      related low back injuries based on the mechanical loading model as one category
      of LBP classification. The methods used for estimation of lower back loads vary
      from simple rigid link-segment models to sophisticated, optimization-based finite
      element models. In general, reviewed reports of differences in mechanical loads
      experienced in lower back tissues between patients with LBP and asymptomatic
      individuals are not consistent. Such lack of consistency is primarily due to
      differences in activities under which lower back mechanical loads were
      investigated as well as heterogeneity of patient populations. The ability to
      examine trunk neuromuscular behavior is particularly relevant to the motor
      control model, another category of LBP classification. LA-SEMG not only is
      noninvasive but also provides spatial resolution within and across muscle groups.
      Studies using LA-SEMG showed that healthy individuals exhibit highly organized,
      symmetric back muscle activity patterns, suggesting an orderly recruitment of
      muscle fibers. In contrast, back muscle activity patterns in LBP patients are
      asymmetric or multifocal, suggesting lack of orderly muscle recruitment. LA-SEMG
      was also shown capable of capturing unique back muscle response to manual
      therapy. In conclusion, estimation of low back load and LA-SEMG techniques
      demonstrated promising potentials for understanding LBP and treatment effects.
      Future studies are warranted to fully establish clinical validity of these two
      biomechanical methods.

PMID- 28761373
TI  - Chronic constriction injury of sciatic nerve changes circular RNA expression in
      rat spinal dorsal horn.
AB  - BACKGROUND: Mechanisms of neuropathic pain are still largely unknown. Molecular
      changes in spinal dorsal horn may contribute to the initiation and development of
      neuropathic pain. Circular RNAs (circRNAs) have been identified as microRNA
      sponges and involved in various biological processes, but whether their
      expression profile changes in neuropathic pain condition is not reported.
      METHODS: To test whether neuropathic pain influences circRNA expression, we
      developed a sciatic chronic constriction injury (CCI) model in rats. The CCI
      ipsilateral spinal dorsal horns of lumbar enlargement segments (L3-L5) were
      collected, and the total RNA was extracted and subjected to Arraystar Rat circRNA
      Microarray. Quantitative real-time polymerase chain reaction (qPCR) was used to
      confirm the circRNA expression profile. To estimate functions of differential
      circRNAs, bioinformatics analyses including gene ontology (GO) and Kyoto
      Encyclopedia of Genes and Genomes Pathway analyses were performed for the top 100
      circRNAs and circRNA-microRNA networks were constructed for the top 10 circRNAs.
      RESULTS: circRNA microarrays showed that 469 circRNAs were differentially
      expressed between CCI and sham-operated rats (fold change >=2). In all, 363 of
      them were significantly upregulated, and the other 106 were downregulated in the
      CCI group. Three of them (circRNA_013779, circRNA_008008, and circRNA_003724)
      overexpressed >10 times after CCI insult. Expression levels of eight circRNAs
      were verified using qPCR. GO analysis revealed that thousands of predicted target
      genes were involved in the biological processes, cellular component, and
      molecular function; in addition, dozens of these genes were enriched in the Hippo
      signaling pathway, MAPK signaling pathway, and so on. Competing endogenous RNAs
      analysis showed that circRNA_008008 and circRNA_013779 are the two largest nodes
      in the circRNA-microRNA interaction network of the top 10 circRNAs. CONCLUSION:
      CCI resulted in a comprehensive expression profile of circRNAs in the spinal
      dorsal horn in rats. CircRNAs in the dorsal horn could be helpful to reveal
      molecular mechanisms of neuropathic pain.

PMID- 28761375
TI  - Continuous transversus abdominis plane block vs intermittent bolus for analgesia
      after abdominal surgery: a randomized trial.
AB  - BACKGROUND: Continuous and intermittent bolus techniques of transversus abdominis
      plane (TAP) blocks have been used for analgesia after abdominal surgery. Although
      both are effective, there are no studies comparing them. The aim of this study is
      to compare analgesia and cost-effectiveness between these groups. METHODS: After
      obtaining ethical approval, 20 American Society of Anesthesiologists ASA grade I
      to III patients undergoing elective abdominal surgery were recruited with 10
      patients allocated to each arm. Bilateral ultrasound-guided TAP blocks were
      performed with an initial bolus of 0.5% ropivacaine 20 mL per side, followed by
      catheter insertion. After surgery, the continuous infusion group received 0.2%
      ropivacaine 8 mL/hour on each side and the intermittent bolus group received
      doses of 0.2% ropivacaine 20 mL per side every 8 hours for 48 hours. Both groups
      received intravenous fentanyl patient-controlled analgesia and regular oral
      paracetamol. Parameters recorded included numerical rating scores for pain and
      post-operative analgesic consumption at baseline (time 0) and at 1 hour, 1 day
      and 2 days post-operatively. The duration of catheter insertion, complications,
      patient satisfaction and information regarding costs were also recorded. Patient
      satisfaction was assessed utilizing a 4-point "Likert" scale on day 2 and on day
      30. Pain and Likert scores were analysed by non-parametric sum rank test and all
      two-sampled t-tests assumed unequal variances. RESULTS: There was no difference
      between duration of TAP block, anesthetic and surgical technique and length of
      stay (p=0.23). Primary outcomes: pain scores at rest and cough were not
      significantly different (p=0.20) between the groups. Satisfaction scores were
      similar at day 2 and 30 (p=0.77). However, the bolus group was more cost
      effective (AU$347.98 vs AU$429.43). CONCLUSION: Continuous or bolus TAP blocks
      are effective analgesic techniques in abdominal surgery, with bolus technique
      being more economical.

PMID- 28761374
TI  - Quality of life during early radiotherapy in patients with head and neck cancer
      and pain.
AB  - BACKGROUND: Patients with head and neck cancer (HNC) have a potentially severe
      diagnosis and often suffer from tumor-related pain as well as from adverse side
      effects of treatment such as radiotherapy (RT). Knowledge about quality of life
      (QoL) during early RT in this group is limited and should be assessed in relation
      to diagnosis and treatment. PURPOSE: The purpose of this cross-sectional study
      was to identify potential factors that may influence QoL in patients with HNC
      during the early stages of RT (no later than two weeks of ongoing RT). We
      hypothesized that pain intensity, pain interference, catastrophizing, and mood
      disturbances are associated with QoL during early RT. PATIENTS AND METHODS: In
      this study, 54 patients (53% of eligible patients) diagnosed with HNC were
      consecutively recruited from the regular flow to the Pain and Rehabilitation
      Center at Linkoping University. The patients completed self-reported
      questionnaires on sociodemographics, pain intensity, pain interference, anxiety,
      depression, pain catastrophizing, and QoL. RESULTS: The patients in this study
      scored high for QoL, low for pain intensity, and low for pain interference. The
      patients reported minor depressive symptoms and anxiety symptoms. Regression
      analyses showed that pain intensity and depressive symptoms negatively influenced
      QoL. CONCLUSION: No later than two weeks of RT, pain intensity and depression
      negatively influenced QoL in patients with HNC. Early screening for pain and
      depression in a targeted preventive strategy might maintain QoL during the course
      of the RT for patients with HNC. This assumption needs to be further
      investigated.

PMID- 28761376
TI  - The impact of examined lymph node count on survival in squamous cell carcinoma
      and adenocarcinoma of the uterine cervix.
AB  - INTRODUCTION: The prognostic impact of the number of examined lymph nodes (ELNs)
      in different histological subtypes of cervical cancer remains unclear. We aimed
      to assess the impact of the number of ELNs in stage IA2-IIA cervical cancer with
      different histological subtypes. METHODS: Data of patients with stage IA2-IIA
      squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the uterine cervix
      between 1988 and 2013 were retrieved from the Surveillance, Epidemiology, and End
      Results program. Univariate and multivariate Cox regression analyses were
      performed to analyze the effect of number of ELNs on cause-specific survival
      (CSS) and overall survival (OS). RESULTS: The final data set identified 11,830
      patients including 7,920 (66.9%) women with SCC and 3,910 (33.1%) with AC. The
      median number of ELNs was 19. The multivariate analysis indicated that the number
      of ELNs was an independent prognostic factor influencing CSS and OS, both as a
      continuous or a categorical variable. Patients with a higher number of ELNs had
      better survival outcomes. In SCC subtype, the number of ELNs was also the
      independent prognostic factor of CSS and OS in node-positive patients, but not in
      patients with node-negative disease. In AC patients, ELN count was not an
      independent predictor of CSS and OS regardless of lymph node status. CONCLUSION:
      The number of ELNs is an independent prognostic factor in patients with stage IA2
      IIB cervical cancer. A higher number of ELNs is associated with better survival
      outcomes, especially in the node-positive SCC subtype.

PMID- 28761378
TI  - Calcium hydroxide liners: a literature review.
AB  - OBJECTIVE: This review integrates the literature on cavity liners and current
      concepts of pulp protection with the aim of establishing a better understanding
      of the role of calcium hydroxide as a cavity liner. MATERIALS AND METHODS: A
      search was conducted through PubMed, MEDLINE, and Ovid for articles with the
      criteria for the following terms: cavity liners and bases, pulp protection, and
      calcium hydroxide liners. No specific inclusion or exclusion criteria were
      applied as to what articles would be included in this review. It was hoped that
      the extent of the literature reviewed would be as comprehensive as possible.
      CONCLUSION: This review underlines the fact that calcium hydroxide liners should
      only be used in the deepest spots in the cavity where the remaining dentine
      thickness is <=0.5 mm. A protective layer of resin-modified glass ionomer should
      always follow the application of calcium hydroxide liners.

PMID- 28761377
TI  - Fecal occult blood versus DNA testing: indirect comparison in a colorectal cancer
      screening population.
AB  - BACKGROUND: A multitarget stool DNA test (MSDT) that showed higher sensitivity
      but lower specificity than a fecal immunochemical test (FIT) for hemoglobin in
      one recent study from the US and Canada, is increasingly used for colorectal
      cancer (CRC) screening, despite its ~20-fold higher costs compared to FITs. We
      aimed to assess diagnostic performance of a quantitative FIT in an independent
      study among participants of screening colonoscopy and to compare it with the
      previously reported performance of MSDT. METHODS: A total of 3494 participants,
      aged 50-84 years, who underwent screening colonoscopy in private
      gastroenterological practices in Germany, and who provided a stool sample before
      colonoscopy to be evaluated by a commercially available quantitative FIT (FOB
      Gold(r)) were included. Diagnostic performance (sensitivity, specificity) for
      detecting CRC or advanced precancerous lesions (APCLs) was evaluated by
      comparison of test results with findings at screening colonoscopy. In addition to
      the original cutoff, we used an adjusted cutoff yielding the same specificity as
      reported for the MSDT to enhance comparability. RESULTS: The most advanced
      finding at colonoscopy was CRC and APCL in 30 (0.86%) and 359 (10.3%) cases,
      respectively. At a cutoff yielding the same specificity as reported for MSDT
      (86.6%), the sensitivities (95% CI) of the FIT for detecting CRC and APCL >1 cm
      were 96.7% (82.8-99.9%) and 54.3% (48.3-60.3%), respectively. These sensitivities
      are higher than those reported for MSDT (92.3% and 43.6%, p=0.66 and 0.003,
      respectively). CONCLUSION: In this large screening population, FIT showed
      equivalent or better diagnostic performance in comparison to reported performance
      of MSDT.

PMID- 28761380
TI  - Corneal deposits associated with topical tosufloxacin following penetrating
      keratoplasty: a case report.
AB  - PURPOSE: To report the adverse event of topical tosufloxacin administered after
      penetrating keratoplasty in one patient. CASE REPORT: A 60-year-old female was
      referred to our hospital for treatment of vision loss due to corneal
      opacification, etiology was unknown. Slit lamp examination showed dense
      opacification in corneal stroma. Penetrating keratoplasty was performed on her
      left eye. She was treated with topical applications of 1.5% levofloxacin, 0.5%
      cefmenoxime, 0.1% betamethasone, 0.1% hyaluronate sodium, and 3% aciclovir after
      penetrating keratoplasty. Delayed epithelialization of the donor graft was
      observed at day 4 post-transplantation. Because of the concern that levofloxacin
      induced corneal epithelialization delay, 1.5% levofloxacin was changed to 0.3%
      tosufloxacin. At day 6 post-transplantation, deposits on the epithelial defect of
      the donor graft were observed. Tosufloxacin was suspected to be the cause of
      deposits, and tosufloxacin eye drop was discontinued. The deposits decreased
      gradually and completely disappeared by 5 months post-transplantation.
      CONCLUSION: Topical tosufloxacin treatment has the risk of precipitation on
      compromised corneas such as corneal grafts with epithelial defect after
      penetrating keratoplasty. After discontinuation of therapy, the deposit may
      resolve spontaneously without surgical removal.

PMID- 28761379
TI  - Effects of nonsurgical periodontal therapy in patients with moderately controlled
      type 2 diabetes mellitus and chronic periodontitis in Nepalese population.
AB  - OBJECTIVES: Despite several investigations, evidence is still controversial
      regarding the effect of periodontal treatment on diabetes. This study evaluates
      and compares the effect on glycemic control and periodontal status with or
      without nonsurgical periodontal therapy in patients with type 2 diabetes mellitus
      and chronic periodontitis in a Nepalese population. MATERIALS AND METHODS: A
      total of 82 patients attending the diabetes clinic and fulfilling enrollment
      criteria with moderate to severe periodontitis were selected. They were assigned
      in an alternative sequence, into test and control group. Both groups were
      instructed to continue with their medical treatment without modifications.
      Scaling and root surface debridement were performed in the test group whereas the
      control group received oral hygiene instructions with no treatment during the 3
      month study period. RESULTS: There were 41 participants in each group with the
      mean age of 50.66+/-7.70 and 53.80+/-9.16 years, average diabetes duration of
      6.32+/-4.21 and 6.24+/-4.00 years, mean body mass index of 24.78+/-1.85 and
      24.6+/-1.79 kg/m2, and glycated hemoglobin (HbA1c) level of 6.71+/-0.50% and
      6.80+/-0.45%, in the test and control group, respectively. After 3 months, there
      was significant reduction in HbA1c levels in the test group compared to the
      control group (p=0.029). Clinical periodontal parameters of gingival index,
      probing depth (PD), and clinical attachment level (CAL) significantly improved in
      the test group (p<0.001) with PD reduction by 0.9 mm and gain in CAL by 0.3 mm
      compared to the control group (p>0.001) who showed an increase by 0.05 mm.
      CONCLUSION: This study showed that nonsurgical periodontal therapy may have a
      beneficial effect on HbA1c level in moderately controlled type 2 diabetic
      patients.

PMID- 28761381
TI  - NMDA receptors are important regulators of pancreatic cancer and are potential
      targets for treatment.
AB  - Pancreatic cancer, particularly adenocarcinoma of the pancreas, is a common
      disease with a poor prognosis. In this study, the importance of N-methyl-D
      aspartate (NMDA) receptors for the growth and survival of pancreatic cancer was
      investigated. Immunohistochemistry performed with antibodies against GluN1 and
      GluN2B revealed that all invasive adenocarcinoma and neuroendocrine pancreatic
      tumors likely express these two NMDA receptor proteins. These proteins were found
      to be membrane components of pancreatic cancer cell lines, and both channel
      blocker antagonist and GluN2B antagonist significantly reduced cell viability in
      vitro. Both types of antagonists caused an internalization of the receptors.
      Dizocilpine maleate (MK-801) and ifenprodil hemitartrate both significantly
      inhibited the growth of pancreatic tumor xenografts in nu/nu mice. These findings
      predict that, as for other solid tumors investigated by us, pancreatic cancer
      could be successfully treated, alone or in combination, with NMDA receptor
      antagonists or other receptor-inhibiting blocking agents.

PMID- 28761382
TI  - Magnetic resonance imaging for assessing hamstring injuries: clinical benefits
      and pitfalls - a review of the current literature.
AB  - Hamstring injuries are common injuries in all levels of athletics. Hamstring
      injuries can cause prolonged absence from sports and have a notorious rate of
      reinjury. Magnetic resonance imaging (MRI) is being increasingly utilized
      following a hamstring injury. Physicians are being increasingly asked to utilize
      MRI to predict clinical outcomes, including time frame for return to play and
      risk of reinjury. In spite of numerous studies in this area, no clear consensus
      exists. The purpose of this paper is to summarize the literature and evidence
      regarding the role of MRI in treating hamstring injuries.

PMID- 28761383
TI  - On the dynamics of disobedience: experimental investigations of defying unjust
      authority.
AB  - Across six Experimental conditions with university student participants (N=600),
      we examined some of the dynamics underlying expressed defiance to unjust
      authority. Results revealed disobedience was best enacted by participants low in
      right-wing authoritarianism and was more likely to occur when: 1) in physical
      proximity of other rebels, 2) the authority made two demanding requests instead
      of one, and 3) there had been an earlier opposition to injustice. Results are
      discussed within the theoretical framework of bounded rationality.

PMID- 28761384
TI  - New PD-L1 inhibitors in non-small cell lung cancer - impact of atezolizumab.
AB  - The era of immunotherapy has changed the face of how we approach treatment for
      many oncologic and hematologic malignancies. Lung cancer has been in the
      forefront of checkpoint inhibition for the past 2 years and has paved the path
      for other subspecialties. While PD-1 inhibitors nivolumab and pembrolizumab have
      been approved for non-small cell lung cancer (NSCLC), this review focuses on
      atezolizumab, its landmark studies, and ongoing trials. Atezolizumab is the first
      programmed death ligand 1 (PD-L1) inhibitor to receive US Food and Drug
      Administration (FDA) approval for metastatic NSCLC patients who have progressed
      on frontline chemotherapy. This approval was based on two open-label Phase II
      multicenter trials, POPLAR (NCT01903993) and BIRCH (NCT02031458). Both studies
      revealed a benefit in overall survival (OS), progression-free survival, and
      response rate in the atezolizumab arm when compared to single-agent docetaxol.
      There were also fewest Grade 3-5 treatment-related adverse events (TRAEs) in the
      atezolizumab cohort. The open-label randomized Phase III OAK trial (NCT02008227)
      further established the role of atezolizumab in previously treated NSCLC. This
      study compared atezolizumab with docetaxel in patients with advanced NSCLC
      (squamous or nonsquamous histologies) who had progressed on one to two prior
      chemotherapy regimens. OS in the PD-L1-enriched population was superior in the
      atezolizumab arm (n=241) at 15.7 months compared with docetaxel (n=222) at 10.3
      months (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.58-0.93;
      p=0.0102). Patients lacking PD-L1 also had survival benefit with atezolizumab
      with a median OS (mOS) of 12.6 months versus 8.9 months with chemotherapy (HR
      0.75, 95% CI 0.59-0.96). Benefit was noted in both squamous and nonsquamous NSCLC
      subsets and regardless of PD-L1 expressivity. As seen in the POPLAR and BIRCH
      studies, the toxicity profile was significantly better with immunotherapy. The
      future is unfolding rapidly as new checkpoint inhibitors are gaining FDA
      approval. It is still not known if these agents will be used in combination with
      chemotherapy, with other immune-modulating agents, radiation therapy, or all of
      the above. The results of these studies investigating their use in combination
      with chemotherapy agents, with other immunotherapy agents such as CTLA-4
      inhibitors, and with radiation therapy, are eagerly awaited.

PMID- 28761385
TI  - Contextual modulation revealed by optical imaging exhibits figural asymmetry in
      macaque V1 and V2.
AB  - Neurons in early visual cortical areas are influenced by stimuli presented well
      beyond the confines of their classical receptive fields, endowing them with the
      ability to encode fine-scale features while also having access to the global
      context of the visual scene. This property can potentially define a role for the
      early visual cortex to contribute to a number of important visual functions, such
      as surface segmentation and figure-ground segregation. It is unknown how
      extraclassical response properties conform to the functional architecture of the
      visual cortex, given the high degree of functional specialization in areas V1 and
      V2. We examined the spatial relationships of contextual activations in macaque V1
      and V2 with intrinsic signal optical imaging. Using figure-ground stimulus
      configurations defined by orientation or motion, we found that extraclassical
      modulation is restricted to the cortical representations of the figural component
      of the stimulus. These modulations were positive in sign, suggesting a relative
      enhancement in neuronal activity that may reflect an excitatory influence.
      Orientation and motion cues produced similar patterns of activation that
      traversed the functional subdivisions of V2. The asymmetrical nature of the
      enhancement demonstrated the capacity for visual cortical areas as early as V1 to
      contribute to figure-ground segregation, and the results suggest that this
      information can be extracted from the population activity constrained only by
      retinotopy, and not the underlying functional organization.

PMID- 28761386
TI  - Effectiveness of teaching facial anatomy through cadaver dissection on aesthetic
      physicians' knowledge.
AB  - BACKGROUND: Cadaver dissection for anatomy training provides an opportunity to
      understand the precise nature of human tissues with their clinical and structural
      relationships. This study assessed the effectiveness of this practical
      educational intervention for teaching applied facial anatomy on the knowledge and
      confidence of aesthetic physicians. METHODS AND MATERIALS: A total of 168
      aesthetic physicians underwent facial applied anatomy training for 2 days at The
      Academia, Singapore. The 2-day course encompassed detailed facial anatomy of
      neurovasculature, fat compartments, ligaments, and muscles followed by simulated
      practice of safer injection techniques. To enable quality interaction between the
      participants and the faculties, the delegates were divided into four groups.
      Academic impact of the program was evaluated by a pre-course and post-course
      multiple choice question (MCQ) test. Participants, also completed a paper-based
      feedback on their knowledge, skills, and confidence in performing nonsurgical
      facial aesthetic procedures. Different sets of MCQs were utilized for pre-course
      post-course test to avoid any recall bias. RESULTS: All 168 participants
      completed the test and were included in the analysis. Mean pre-course and post
      course test scores were 4.8 (standard deviation [SD] 1.9) and 7.6 (SD 1.7),
      respectively (p<0.001 vs pre-course test). All the four groups showed improvement
      in their facial anatomy knowledge based on the comparison of pre-course and post
      course test results (p<0.001). The average post-course test score in all the
      groups from baseline significantly improved. However, there was no statistical
      difference in pre-course and post-course test evaluation between the groups
      (p=0.32). CONCLUSION: Our results showed that cadaver anatomy training improved
      applied facial anatomy knowledge for most of the aesthetic practitioners, which
      may enhance their confidence in performing nonsurgical facial aesthetic
      procedures.

PMID- 28761387
TI  - Abortion, an increasing public health concern in Ecuador, a 10-year population
      based analysis.
AB  - OBJECTIVES: To describe the epidemiology of abortion in Ecuador from 2004 to 2014
      and compare the prevalence between the public and the private health care
      systems. METHODS: This is a cross-sectional analysis of the overall mortality and
      morbidity rate due to abortion in Ecuador, based on public health records and
      other government databases. RESULTS: From 2004 to 2014, a total of 431,614
      spontaneous abortions, miscarriage and other types of abortions were registered
      in Ecuador. The average annual rate of abortion was 115 per 1,000 live births.
      The maternal mortality rate was found to be 43 per 100,000 live births.
      CONCLUSIONS: Abortion is a significant and wide-ranging problem in Ecuador. The
      study supports the perception that in spite of legal restrictions to abortion in
      Ecuador, women are still terminating pregnancies when they feel they need to do
      so. The public health system reported >84% of the national overall prevalence.

PMID- 28761389
TI  - Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic
      Desmoid Tumors.
AB  - Desmoid tumors are locally aggressive fibroproliferative neoplasms that can lead
      to pain and dysfunction due to compression of nerves and surrounding structures.
      Desmoid tumors often progress through medical therapy, and there is frequently a
      delay of multiple months before radiation can provide symptomatic relief. To
      achieve more rapid symptomatic relief and tumor regression for unresectable
      desmoid tumors causing significant morbidity such as brachial plexus impingement
      with loss of extremity function, we have selectively utilized a combination of
      imatinib and radiation therapy. Here, we retrospectively review four patients
      treated with concurrent imatinib and radiation therapy. The treatment was
      typically tolerated with minimal toxicity though one patient developed avascular
      necrosis of the irradiated humeral head possibly related to the combined
      treatment. All the patients treated have had a partial response or stable disease
      on imaging. Improvement of symptoms was observed in all the treated patients with
      a median time to relief of 2.5 months after starting radiation therapy.
      Concurrent radiation and imatinib may represent a viable treatment option for
      unresectable and symptomatic desmoid tumors where rapid relief is needed to
      prevent permanent loss of function.

PMID- 28761388
TI  - Coronary stents and vascular response to implantation: literature review.
AB  - Drug-eluting stents (DESs) have minimized the limitations of bare-metal stents
      (BMSs) after percutaneous coronary interventions. Nevertheless, serious concerns
      remain about possible late complications of stenting, such as stent thrombosis
      (ST) and in-stent restenosis (ISR), although the introduction of second
      generation DESs seems to have softened the phenomenon, compared to the first
      generation ones. ST is a potentially catastrophic event, which has been markedly
      reduced by optimization of stent implantation, novel stent designs, and dual
      antiplatelet therapy. The exact mechanism to explain its occurrence is under
      investigation, and, realistically, multiple factors are responsible. ISR of BMSs
      has been previously considered as a stable condition with an early peak (at 6
      months) of intimal hyperplasia, followed by a regression period beyond 1 year. On
      the contrary, both clinical and histologic studies of DESs have demonstrated
      evidence of continuous neointimal growth during long-term follow-up, named "late
      catch-up" phenomenon. The acknowledgment that ISR is a relatively benign clinical
      condition has been recently challenged by evidences which reported that patients
      with ISR can experience acute coronary syndromes. Intracoronary imaging is an
      invasive technology that allows identifying features of atherosclerotic plaque of
      stent implanted and of vascular healing after stenting; it is often used to
      complete diagnostic coronary angiography and to drive interventional procedures.
      Intracoronary optical coherence tomography is currently considered a state-of-the
      art imaging technique; it provides, compared to intravascular ultrasound, better
      resolution (at least >10 times), allowing the detailed characterization of the
      superficial structure of the vessel wall. Imaging studies "in vivo," in agreement
      with histological findings, suggest that chronic inflammation and/or endothelial
      dysfunction may induce late de novo "neoatherosclerosis" inside both BMSs and
      DESs. So, neoatherosclerosis has become the prime suspect in the pathogenesis of
      late stent failure.

PMID- 28761390
TI  - Intensity-modulated radiation therapy for small cell carcinoma of the prostate: A
      case report.
AB  - Small cell carcinomas (SCC) make up only 1% of malignancies of the prostate.
      Reports of several case series have described outcomes of surgery and
      chemotherapy for SCC of the prostate, but few reports address radiotherapy. We
      treated a case of SCC of the prostate with intensity-modulated radiation therapy
      (IMRT) consisting of 70 Gy administered in 35 fractions followed by hormonal
      therapy using only luteinizing hormone-releasing hormone (LH-RH) agonist. The
      tumor volume decreased remarkably by 4 months after IMRT. The rapid decrease in
      tumor size of this SCC of the prostate seemed to suggest a similar high
      radiosensitivity to that of SCC of the lung, but the tumor increased rapidly
      thereafter within the radiation fields, and pelvic lymph node metastases had
      developed by 24 months after IMRT. By 28 months after IMRT, multiple lung
      metastases developed, and the patient died of SCC of the prostate 31 months after
      initial diagnosis.

PMID- 28761391
TI  - The accuracy of treatment planning system dose modelling in the presence of brass
      mesh bolus.
AB  - AIM: This work assesses the dosimetric accuracy of three commercial treatment
      planning system (TPS) photon dose calculation algorithms in the presence of brass
      mesh used as a bolus. BACKGROUND: Bolus material is used in radiotherapy to
      provide dose build-up where superficial tissues require irradiation. They are
      generally water equivalent but high density materials can also be used. MATERIALS
      AND METHODS: Dose calculations were performed on Monaco and Masterplan TPS
      (Elekta AB, Sweden) using phantoms defined by the three DICOM CT image sets of
      water equivalent blocks (no bolus, 1 layer and 2 layers of brass mesh) exported
      from the CT scanner. The effect of the mesh on monitor units, build-up dose,
      phantom exit dose and beam penumbra were compared to measured data. RESULTS: Dose
      calculations for 6 and 15 MV photon beams on plain water equivalent phantoms were
      seen to agree well with measurement validating the basic planning system
      algorithms and models. Dose in the build-up region, phantom exit dose and beam
      penumbra were poorly modelled in the presence of the brass mesh. The beam
      attenuation created by the bolus material was overestimated by all three
      calculation algorithms, at both photon energies, e.g. 1.6% for one layer and up
      to 3.1% for two layers at 6 MV. The poor modelling of the physical situation in
      the build-up region is in part a consequence of the high HU artefact caused by
      the mesh in the CT image. CONCLUSIONS: CT imaging is not recommended with the
      brass mesh bolus in situ due to the poor accuracy of the subsequent TPS
      modelling.

PMID- 28761392
TI  - Assessment of performance indicators of a radiotherapy department using an
      electronic medical record system.
AB  - AIM: To retrospectively assess the performance indicators of our radiotherapy
      department and their temporal trends, using a commercially available electronic
      medical-record (EMR) system. BACKGROUND: A recent trend in healthcare quality is
      to define and evaluate performance indicators of the service provided. MATERIALS
      AND METHODS: Patient and external-beam-radiotherapy-treatments data were
      retrieved using the Mosaiq EMR system from 1-January-2012 till 31-December-2015.
      Annual performance indicators were evaluated as: productivity (number of new
      cases/year and diagnosis distribution); complexity (ratio of Volumetric-Modulated
      Arc-Therapy (VMAT) courses, average number of imaging procedures/patient); and
      quality (average, median and 90th percentile waiting times from admission to
      first treatment). The temporal trends of all performance indicators were assessed
      by linear regression. RESULTS: Productivity: the number of new cases/year
      increased with an average rate of 4%. Diagnosis distribution showed that breast
      is the main pathology treated, followed by gastro-intestinal and head-and-neck.
      Complexity: the ratio of VMAT courses increased from 13% to 35%, with an average
      rate of 7% per year. The average number of imaging procedures/patient increased
      from 8 to 11. Quality: the waiting times from admission to treatment remained
      stable over time (R2 <= 0.1), with average, median and 90th percentile values
      around 20, 15, and 31 days, respectively. CONCLUSIONS: An EMR system can be used
      to: monitor the performance indicators of a radiotherapy department, identify
      workflow processes needing attention and improvement, estimate future demands of
      resources. Temporal analysis of our data showed an increasing trend in
      productivity and complexity paired with constant waiting times.

PMID- 28761393
TI  - A Combined Intravascular MRI Endoscope and Intravascular Ultrasound (IVUS)
      Transducer for High-Resolution Image-Guided Ablation.
AB  - An intravascular MRI (IMRI) loopless antenna is combined for the first time with
      an intravascular water-cooled ultrasound ablation transducer as a possible tool
      for providing high-resolution MRI-guided ablations of pathological tissue via
      intravascular access. High resolution anatomical MRI, and real-time MRI
      thermometry were used to monitor ablation delivery in phantoms and tissue
      specimens. Results show that IMRI can guide IVUS-mediated directional ablation
      with minimal image artifacts. This permits the monitoring of thermal dose and
      therapy titration while minimizing potential thermal damage to the vessel wall.

PMID- 28761394
TI  - James E. Bagg, Jr.: Editor par Excellence Retires.

PMID- 28761395
TI  - More on the Science of Health Care.

PMID- 28761396
TI  - Unproven Stem Cell-Based Interventions: Advancing Policy through Stakeholder
      Collaboration.

PMID- 28761397
TI  - Clara's Final Christmas Gift.

PMID- 28761398
TI  - White Blood Cell Subtypes Are Associated with a Greater Long-Term Risk of Death
      after Acute Myocardial Infarction.
AB  - We evaluated the association between white blood cell counts and long-term
      mortality rates in 2,129 patients (mean age, 65.3 +/- 13.5 yr; 69% men) who had
      survived acute myocardial infarction. We obtained white blood cell counts and
      differential counts of white blood cell subtypes within the first 72 hours of
      hospital admission. The primary outcome was all-cause death at 1, 5, and 10 years
      after acute myocardial infarction. In regard to death in the long term, we found
      significant negative linear associations (lymphocytes), positive linear
      associations (neutrophils and the neutrophil-to-lymphocyte ratio), and nonlinear
      U-shaped associations (basophils, eosinophils, monocytes, and total white blood
      cell count). After multivariate adjustment for the Soroka Acute Myocardial
      Infarction risk score, lymphocytes (strongest association), neutrophil-to
      lymphocyte ratio, and eosinophils were independently associated with death for up
      to 10 years after hospital discharge. The independent associations weakened over
      time. We conclude that lymphocyte count, neutrophil-to-lymphocyte ratio, and
      eosinophil count are independently and incrementally associated with death in the
      long term after acute myocardial infarction.

PMID- 28761400
TI  - The Two Anomalies of Wilhelm Ebstein.
AB  - The year 2016 was the 180th anniversary of Wilhelm Ebstein's birth and the 150th
      anniversary of his description of the congenital tricuspid valve malformation
      that came to be known as Ebstein anomaly. We present a brief history of the life
      and work of Dr. Wilhelm Ebstein. Despite his distinguished career, he is
      seemingly forgotten in his own birthplace. We include a review of the relevant
      historical medical literature.

PMID- 28761399
TI  - Potential Role of Patent Foramen Ovale in Exacerbating Hypoxemia in Chronic
      Pulmonary Disease.
AB  - Patent foramen ovale has been associated with multiple pulmonary diseases, such
      as pulmonary hypertension, platypnea-orthodeoxia syndrome, and chronic
      obstructive pulmonary disease. A connection between patent foramen ovale and
      chronic pulmonary disease was first described more than 2 decades ago in case
      reports associating patent foramen ovale with more severe hypoxemia than that
      expected based on the severity of the primary pulmonary disease. It has been
      suggested that patients with both chronic pulmonary disease and patent foramen
      ovale are subject to severe hypoxemia because of the right-to-left shunt.
      Furthermore, investigators have reported improved systemic oxygenation after
      patent foramen ovale closure in some patients with chronic pulmonary disease.
      This review focuses on the association between chronic pulmonary disease and
      patent foramen ovale and on the dynamics of a right-to-left shunt, and it
      considers the potential benefit of patent foramen ovale closure in patients who
      have hypoxemia that is excessive in relation to the degree of their pulmonary
      disease.

PMID- 28761401
TI  - Modified Port-Access Technique for the Treatment of Aortic Dissection after
      Previous Cardiac Surgery.
AB  - One of the most challenging conditions to manage after previous cardiac surgery
      is chronic dissection of the ascending aorta. We operated on a 54-year-old man
      who had aortic dissection in addition to large aortic dimensions very close to
      the sternum, severe aortic regurgitation, and a false lumen in the descending
      aorta. We used a combination of perfusion and myocardial protection techniques,
      arising from port-access technology, that enabled antegrade flow into the aorta,
      endoclamping of the ascending aorta, the administration of cardioplegic solution
      before opening the sternum, and left ventricular venting to prevent ventricular
      distention. Our technique resulted in minimal blood loss, shorter circulatory
      arrest and operative times, the ability to operate on a decompressed heart and
      descending aorta, good myocardial protection, and easier and safer access to the
      heart. Three years postoperatively, our patient was doing well. Other patients
      might benefit from this approach; however, the surgeon must ensure that an aortic
      segment is suitable for endoclamping.

PMID- 28761402
TI  - Posterior Reversible Encephalopathy Syndrome after Heart Transplantation:
      Diagnosis and Immunosuppressive Therapy.
AB  - Posterior reversible encephalopathy syndrome, an infrequent neurotoxicity
      associated with the use of tacrolimus, was first described in 1996, as a
      reversible syndrome manifested by headache, altered mental function, seizures,
      and visual disturbances. We describe the case of a 37-year-old woman who
      developed neurologic symptoms consistent with encephalopathy after treatment with
      tacrolimus, which was prescribed to maintain immunosuppression after orthotopic
      heart transplantation. This report also discusses the imaging methods used in the
      diagnosis of posterior reversible encephalopathy and highlights the difficulty of
      maintaining immunosuppression and managing medication-related adverse effects,
      while taking into account the risk of acute rejection after transplantation.

PMID- 28761403
TI  - Transcatheter Tricuspid Valve-in-Valve Replacement with an Edwards Sapien 3
      Valve.
AB  - A few case reports and case series have documented the outcomes in patients with
      tricuspid bioprosthetic valvular degeneration who underwent transcatheter
      implantation of the Medtronic Melody and the Edwards Sapien XT and Sapien 3
      valves. In this report, we describe the case of a 49-year-old woman with severe
      bioprosthetic tricuspid valvular stenosis and multiple comorbidities who
      underwent transcatheter tricuspid valve replacement with a Sapien 3 valve.

PMID- 28761404
TI  - Left Internal Thoracic Artery Graft to Left Anterior Descending Coronary Artery
      after Blunt-Chest-Trauma Myocardial Infarction: 14-Year Outcome.
AB  - In 2005, we reported an acute myocardial infarction secondary to a left anterior
      descending coronary artery injury sustained in a motorcycle accident. The
      treatment was late myocardial revascularization with in situ left internal
      thoracic artery-to-left anterior descending coronary artery anastomosis. There is
      little information available about the natural history of acute myocardial
      infarction after blunt chest trauma, especially when treated in this manner. This
      present communication reports the 14-year outcome in our patient.

PMID- 28761406
TI  - Position of Subcutaneous Implantable Cardioverter-Defibrillators and Possible
      Interference on Myocardial Perfusion Imaging.
AB  - Implanted cardioverter-defibrillators can prevent sudden cardiac death in at-risk
      patients. In comparison with conventional transvenous systems, entirely
      subcutaneous implantable cardioverter-defibrillators have produced similar
      reductions in the rate of sudden cardiac death but with fewer sequelae. An
      infrequently reported drawback of subcutaneous devices, however, is the potential
      for generating attenuation artifact during nuclear myocardial perfusion imaging.
      We had concerns about potential attenuation artifact in a 65-year-old man with
      coronary artery disease but found that having positioned the pulse generator in
      the midaxillary zone avoided problems.

PMID- 28761405
TI  - Eosinophilia and Ulcerative Colitis Associated with Eosinophilic Myocarditis.
AB  - Reactive eosinophilia is associated with inflammatory bowel disease, but its
      association with eosinophilic myocarditis is rare. We report a case of a 42-year
      old man who presented with hypovolemic shock secondary to diarrhea and recently
      diagnosed nonischemic cardiomyopathy (left ventricular ejection fraction, 0.29).
      Laboratory evaluation revealed marked peripheral eosinophilia. Cardiac magnetic
      resonance imaging showed evidence of subacute-to-chronic myocarditis, and
      endomyocardial biopsy results were consistent with eosinophilic myocarditis.
      Colonic biopsy specimens revealed ulcerative colitis and no eosinophils.
      Hematologic evaluation was negative for an alternative cause of eosinophilia. The
      patient was given corticosteroids; his diarrhea resolved, but there was no short
      term improvement in his ejection fraction, so an implantable cardioverter
      defibrillator was placed. Follow-up at one year showed that the patient's left
      ventricular ejection fraction had improved to 0.42.

PMID- 28761407
TI  - Evaluation of Chest Pain after Implantable Cardioverter-Defibrillator Placement.

PMID- 28761408
TI  - Diastolic Mitral Regurgitation in Complete Heart Block.

PMID- 28761409
TI  - Psychoactive Substance Use among Methadone Maintenance Therapy Clients in China.
AB  - A proportion of methadone maintenance therapy (MMT) clients in China shifted
      their substance use habit from opiate to psychoactive substances. The objective
      of this study was to examine the pattern and associated factors of psychoactive
      substance use among MMT clients. The study was conducted among 2,448 clients from
      68 MMT clinics of China. The type and frequency of psychoactive substance use
      were self-reported. About 38.1% (N=933) of the participants reported psychoactive
      substance use in lifetime, and 6.5% (N=158) in the previous 30 days. The most
      commonly used psychoactive substances were sedative/hypnotic/antidiarrheal agent
      and amphetamine. Psychoactive substance use in the past 30 days was correlated
      with younger age, recent heroin use, having psychoactive substance using
      friend(s), and depressive symptoms. The finding suggested that urinalysis of
      psychoactive substances should be routinely administered in the MMT clinics.
      Young clients, concurrent heroin users, and clients with depressive symptoms
      deserve more screening and intervention efforts.

PMID- 28761410
TI  - Correction: Acupuncture with reinforcing and reducing twirling manipulation
      inhibits hippocampal neuronal apoptosis in spontaneously hypertensive rats.
AB  - [This corrects the article on p. 770 in vol. 12, PMID: 28616034.].

PMID- 28761412
TI  - Immunomodulators and microRNAs as neurorestorative therapy for ischemic stroke.
AB  - Most of all strokes are ischemic due to occlusion of a vessel, and comprise two
      main types, thrombotic and embolic. Inflammation and immune response play an
      important role in the outcome of ischemic stroke. Pharmaceutical and cell-based
      therapies with immunomodulatory properties could be of benefit in treating
      ischemic stroke. Possible changes in microRNAs brought about by immunomodulatory
      treatments may be important. The pharmaceutical studies described in this review
      have identified several differentially regulated miRNAs associated with
      disregulation of mRNA targets or the upregulation of several neuroprotective
      genes, thereby highlighting the potential neuroprotective roles of specific
      miRNAs such as miR-762, -1892, -200a, -145. MiR-124, -711, -145 are the strongly
      associated miRNAs predicted to mediate anti-inflammatory pathways and
      microglia/macrophage M2-like activation phenotype. The cell-based therapy studies
      reviewed have mainly utilized mesenchymal stem cells or human umbilical cord
      blood cells and shown to improve functional and neurological outcomes in stroke
      animals. MiR-145 and miR-133b were implicated in nerve cell remodeling and
      functional recovery after stroke. Human umbilical cord blood cells decreased
      proinflammatory factors and promoted M2 macrophage polarization in stroke
      diabetic animals.

PMID- 28761413
TI  - Curcuma longa L. extract improves the cortical neural connectivity during the
      aging process.
AB  - Turmeric or Curcuma is a natural product that has anti-inflammatory, antioxidant
      and anti-apoptotic pharmacological properties. It can be used in the control of
      the aging process that involves oxidative stress, inflammation, and apoptosis.
      Aging is a physiological process that affects higher cortical and cognitive
      functions with a reduction in learning and memory, limited judgment and deficits
      in emotional control and social behavior. Moreover, aging is a major risk factor
      for the appearance of several disorders such as cerebrovascular disease, diabetes
      mellitus, and hypertension. At the brain level, the aging process alters the
      synaptic intercommunication by a reduction in the dendritic arbor as well as the
      number of the dendritic spine in the pyramidal neurons of the prefrontal cortex,
      hippocampus and basolateral amygdala, consequently reducing the size of these
      regions. The present review discusses the synaptic changes caused by the aging
      process and the neuroprotective role the Curcuma has through its anti
      inflammatory, antioxidant and anti-apoptotic actions.

PMID- 28761411
TI  - The crossed phrenic phenomenon.
AB  - The cervical spine is the most common site of traumatic vertebral column
      injuries. Respiratory insufficiency constitutes a significant proportion of the
      morbidity burden and is the most common cause of mortality in these patients. In
      seeking to enhance our capacity to treat specifically the respiratory dysfunction
      following spinal cord injury, investigators have studied the "crossed phrenic
      phenomenon", wherein contraction of a hemidiaphragm paralyzed by a complete
      hemisection of the ipsilateral cervical spinal cord above the phrenic nucleus can
      be induced by respiratory stressors and recovers spontaneously over time.
      Strengthening of latent contralateral projections to the phrenic nucleus and
      sprouting of new descending axons have been proposed as mechanisms contributing
      to the observed recovery. We have recently demonstrated recovery of spontaneous
      crossed phrenic activity occurring over minutes to hours in C1-hemisected
      unanesthetized decerebrate rats. The specific neurochemical and molecular
      pathways underlying crossed phrenic activity following injury require further
      clarification. A thorough understanding of these is necessary in order to develop
      targeted therapies for respiratory neurorehabilitation following spinal trauma.
      Animal studies provide preliminary evidence for the utility of
      neuropharmacological manipulation of serotonergic and adenosinergic pathways,
      nerve grafts, olfactory ensheathing cells, intraspinal microstimulation and a
      possible role for dorsal rhizotomy in recovering phrenic activity following
      spinal cord injury.

PMID- 28761414
TI  - Novel aspects of extracellular adenosine dynamics revealed by adenosine sensor
      cells.
AB  - Adenosine modulates diverse physiological and pathological processes in the
      brain, including neuronal activities, blood flow, and inflammation. However, the
      mechanisms underlying the dynamics of extracellular adenosine are not fully
      understood. We have recently developed a novel biosensor, called an adenosine
      sensor cell, and we have characterized the neuronal and astrocytic pathways for
      elevating extracellular adenosine. In this review, the physiological implications
      and therapeutic potential of the pathways revealed by the adenosine sensor cells
      are discussed. We propose that the multiple pathways regulating extracellular
      adenosine allow for the diverse functions of this neuromodulator, and their
      malfunctions cause various neurological and psychiatric disorders.

PMID- 28761415
TI  - Dual and multi-drug delivery nanoparticles towards neuronal survival and synaptic
      repair.
AB  - Among the macromolecular drug targets in neurodegenerative disorders, the
      neurotrophin brain-derived neurotrophic factor (BDNF) and its high-affinity
      tropomyosin-related kinase receptor (TrkB) present strong interest for
      nanomedicine development aiming at neuronal and synaptic repair. Currently, BDNF
      is regarded as the neurotrophic factor of highest therapeutic significance.
      However, BDNF has delivery problems as a protein drug. The enhanced activation of
      the transcription factor CREB (cAMP response element-binding protein) has been
      evidenced to increase the BDNF gene expression and hence the production of
      endogenous BDNF. We assume that BDNF delivery by nanocarriers and mitochondrial
      protection may provide high potential for therapeutic amelioration of the
      neuroregenerative strategies. Beneficial therapeutic outcomes may be expected for
      synergistic dual or multi-drug action aiming at (i) neurotrophic protein
      regulation in the central and peripheral nervous systems, and (ii) diminishment
      of the production of reactive oxygen species (ROS) and the oxidative damage in
      mitochondria. Our research strategy is based on a nanoarchitectonics approach for
      the design of nanomedicine assemblies by hierarchical self-assembly. We explore
      nanoarchitectonics concepts in soft-matter nanotechnology towards preparation of
      biodegradable self-assembled lipid nanostructures for safe neuro-therapeutic
      applications of multi-target nanomedicines.

PMID- 28761416
TI  - Neurological consequences of systemic inflammation in the premature neonate.
AB  - Despite substantial progress in neonatal care over the past two decades leading
      to improved survival of extremely premature infants, extreme prematurity
      continues to be associated with long term neurodevelopmental impairments.
      Cerebral white matter injury is the predominant form of insult in preterm brain
      leading to adverse neurological consequences. Such brain injury pattern and
      unfavorable neurologic sequelae is commonly encountered in premature infants
      exposed to systemic inflammatory states such as clinical or culture proven sepsis
      with or without evidence of meningitis, prolonged mechanical ventilation,
      bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis.
      Underlying mechanisms may include cytokine mediated processes without direct
      entry of pathogens into the brain, developmental differences in immune response
      and complex neurovascular barrier system that play a critical role in regulating
      the cerebral response to various systemic inflammatory insults in premature
      infants. Understanding of these pathologic mechanisms and clinical correlates of
      such injury based on serum biomarkers or brain imaging findings on magnetic
      resonance imaging will pave way for future research and translational therapeutic
      opportunities for the developing brain.

PMID- 28761417
TI  - On the role of endogenous neurotoxins and neuroprotection in Parkinson's disease.
AB  - For 50 years ago was introduced L-3,4-dihydroxyphenylalanine (L-dopa) in
      Parkinson's disease treatment and during this significant advances has been done
      but what trigger the degeneration of the nigrostriatal system remain unknown.
      There is a general agreement in the scientific community that mitochondrial
      dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to
      neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum
      stress are involved in the loss of dopaminergic neurons containing neuromelanin
      in Parkinson's disease. The question is what triggers these mechanisms. The age
      of normal onset in idiopathic Parkinson's disease suggests that environmental
      factors such as metals, pollutants or genetic mutations cannot be involved
      because these factors are related to early onset of Parkinsonism. Therefore, we
      have to search for endogenous neurotoxins and neuroprotection in order to
      understand what trigger the loss of dopaminergic neurons. One important feature
      of Parkinson's disease is the rate of the degenerative process before the motor
      symptoms are evident and during the disease progression. The extremely slow rate
      of Parkinson's disease suggests that the neurotoxins and the neuroprotection have
      to be related to dopamine metabolism. Possible candidates for endogenous
      neurotoxins are alpha-synuclein neurotoxic oligomers, 4
      dihydroxyphenylacetaldehyde and ortho-quinones formed during dopamine oxidation
      to neuromelanin. Vesicular monoamine transporter-2, DT-diaphorase and glutathione
      transferase M2-2 seems to be the most important neuroprotective mechanism to
      prevent neurotoxic mechanism during dopamine oxidation.

PMID- 28761418
TI  - The interaction of genetics and environmental toxicants in amyotrophic lateral
      sclerosis: results from animal models.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease
      that results in the progressive death of motor neurons, leading to paralysis and
      eventual death. There is presently no cure for ALS, and only two drugs are
      available, neither of which provide significant extension of life. The wide
      variation in onset and progression of the disease, both in sporadic and even in
      strongly penetrant monogenic familial forms of ALS, indicate that in addition to
      background genetic variation impacting the disease process, environmental
      exposures are likely contributors. Epidemiological evidence worldwide implicates
      exposures to bacterial toxins, heavy metals, pesticides, and trauma as probable
      environmental factors. Here, we review current advances in gene-environment
      interactions in ALS animal models. We report our recent discoveries in a
      zebrafish model of ALS in relation to exposure to the cyanobacterial toxin BMAA,
      and discuss several results from mouse models that show interactions with
      exposure to mercury and statin drugs, both leading to acceleration of the disease
      process. The increasing research into this combinatorial gene-environment process
      is just starting, but shows early promise to uncover the underlying biochemical
      pathways that instigate the initial motor neuron defects and lead to their
      rapidly progressive dysfunction.

PMID- 28761419
TI  - Interfacing peripheral nerve with macro-sieve electrodes following spinal cord
      injury.
AB  - Macro-sieve electrodes were implanted in the sciatic nerve of five adult male
      Lewis rats following spinal cord injury to assess the ability of the macro-sieve
      electrode to interface regenerated peripheral nerve fibers post-spinal cord
      injury. Each spinal cord injury was performed via right lateral hemisection of
      the cord at the T9-10 site. Five months post-implantation, the ability of the
      macro-sieve electrode to interface the regenerated nerve was assessed by
      stimulating through the macro-sieve electrode and recording both electromyography
      signals and evoked muscle force from distal musculature. Electromyography
      measurements were recorded from the tibialis anterior and gastrocnemius muscles,
      while evoked muscle force measurements were recorded from the tibialis anterior,
      extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode
      and regenerated sciatic nerve were then explanted for histological evaluation.
      Successful sciatic nerve regeneration across the macro-sieve electrode interface
      following spinal cord injury was seen in all five animals. Recorded
      electromyography signals and muscle force recordings obtained through macro-sieve
      electrode stimulation confirm the ability of the macro-sieve electrode to
      successfully recruit distal musculature in this injury model. Taken together,
      these results demonstrate the macro-sieve electrode as a viable interface for
      peripheral nerve stimulation in the context of spinal cord injury.

PMID- 28761420
TI  - Repurposing cancer drugs to treat neurological diseases - Src inhibitors as
      examples.

PMID- 28761421
TI  - The use of localized proteomics to identify the drivers of Alzheimer's disease
      pathogenesis.

PMID- 28761422
TI  - Heparan sulfate proteoglycans and heparanases in Alzheimer's disease: current
      outlook and potential therapeutic targets.

PMID- 28761423
TI  - Galantamine protects against beta amyloid peptide-induced DNA damage in a model
      for Alzheimer's disease.

PMID- 28761424
TI  - Neuroprotective effects of ischemic preconditioning on hippocampal CA1 pyramidal
      neurons through maintaining calbindin D28k immunoreactivity following subsequent
      transient cerebral ischemia.
AB  - Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow
      has been applied for an experimental therapeutic strategy against a subsequent
      fatal ischemic insult. In this study, we investigated the neuroprotective effects
      of ischemic preconditioning (2-minute transient cerebral ischemia) on calbindin
      D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent
      fatal transient ischemic insult (5-minute transient cerebral ischemia). A large
      number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5
      minute transient cerebral ischemia. Ischemic preconditioning reduced the death of
      pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity
      was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and
      it was hardly detected at 5 days post-ischemia. Ischemic preconditioning
      maintained calbindin D28k immunoreactivity after transient cerebral ischemia.
      These findings suggest that ischemic preconditioning can attenuate transient
      cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1
      area through maintaining calbindin D28k immunoreactivity.

PMID- 28761425
TI  - Electroacupuncture regulates the stress-injury-repair chain of events after
      cerebral ischemia/reperfusion injury.
AB  - Inflammation after stroke is the main cause of cerebral ischemia/reperfusion
      injury. Cascading events after injury can lead to cell death. Heat shock protein
      70 and other endogenous injury-signaling molecules are released by damaged cells,
      which can lead to systemic stress reactions. Protecting the brain through repair
      begins with the stress-injury-repair signaling chain. This study aimed to verify
      whether acupuncture acts through this chain to facilitate effective treatment of
      ischemic stroke. Rat models of cerebral ischemia/reperfusion injury were
      established by Zea Longa's method, and injury sites were identified by assessing
      neurological function, 2,3,5-triphenyltetrazolium chloride staining, and
      hematoxylin-eosin staining. Electroacupuncture at acupoints Baihui (DU20) and
      Zusanli (ST36) was performed in the model rats with dilatational waves, delivered
      for 20 minutes a day at 2-100 Hz and an amplitude of 2 mA. We analyzed the blood
      serum from the rats and found that inflammatory cytokines affected the levels of
      adrenotrophin and heat shock protein 70, each of which followed a similar bimodal
      curve. Specifically, electroacupuncture lowered the peak levels of
      adrenocorticotrophic hormone and heat shock protein 70. Thus, electroacupuncture
      was able to inhibit excessive stress, reduce inflammation, and promote the repair
      of neurons, which facilitated healing of ischemic stroke.

PMID- 28761426
TI  - Metabolite changes in the ipsilateral and contralateral cerebral hemispheres in
      rats with middle cerebral artery occlusion.
AB  - Cerebral ischemia not only causes pathological changes in the ischemic areas but
      also induces a series of secondary changes in more distal brain regions (such as
      the contralateral cerebral hemisphere). The impact of supratentorial lesions,
      which are the most common type of lesion, on the contralateral cerebellum has
      been studied in patients by positron emission tomography, single photon emission
      computed tomography, magnetic resonance imaging and diffusion tensor imaging. In
      the present study, we investigated metabolite changes in the contralateral
      cerebral hemisphere after supratentorial unilateral ischemia using nuclear
      magnetic resonance spectroscopy-based metabonomics. The permanent middle cerebral
      artery occlusion model of ischemic stroke was established in rats. Rats were
      randomly divided into the middle cerebral artery occlusion 1-, 3-, 9- and 24-hour
      groups and the sham group. 1H nuclear magnetic resonance spectroscopy was used to
      detect metabolites in the left and right cerebral hemispheres. Compared with the
      sham group, the concentrations of lactate, alanine, gamma-aminobutyric acid,
      choline and glycine in the ischemic cerebral hemisphere were increased in the
      acute stage, while the concentrations of N-acetyl aspartate, creatinine,
      glutamate and aspartate were decreased. This demonstrates that there is an
      upregulation of anaerobic glycolysis (shown by the increase in lactate), a
      perturbation of choline metabolism (suggested by the increase in choline),
      neuronal cell damage (shown by the decrease in N-acetyl aspartate) and
      neurotransmitter imbalance (evidenced by the increase in gamma-aminobutyric acid
      and glycine and by the decrease in glutamate and aspartate) in the acute stage of
      cerebral ischemia. In the contralateral hemisphere, the concentrations of
      lactate, alanine, glycine, choline and aspartate were increased, while the
      concentrations of gamma-aminobutyric acid, glutamate and creatinine were
      decreased. This suggests that there is a difference in the metabolite changes
      induced by ischemic injury in the contralateral and ipsilateral cerebral
      hemispheres. Our findings demonstrate the presence of characteristic changes in
      metabolites in the contralateral hemisphere and suggest that they are most likely
      caused by metabolic changes in the ischemic hemisphere.

PMID- 28761427
TI  - High-frequency and brief-pulse stimulation pulses terminate cortical electrical
      stimulation-induced afterdischarges.
AB  - Brief-pulse stimulation at 50 Hz has been shown to terminate afterdischarges
      observed in epilepsy patients. However, the optimal pulse stimulation parameters
      for terminating cortical electrical stimulation-induced afterdischarges remain
      unclear. In the present study, we examined the effects of different brief-pulse
      stimulation frequencies (5, 50 and 100 Hz) on cortical electrical stimulation
      induced afterdischarges in 10 patients with refractory epilepsy. Results
      demonstrated that brief-pulse stimulation could terminate cortical electrical
      stimulation-induced afterdischarges in refractory epilepsy patients. In
      conclusion, (1) a brief-pulse stimulation was more effective when the
      afterdischarge did not extend to the surrounding brain area. (2) A higher brief
      pulse stimulation frequency (especially 100 Hz) was more likely to terminate an
      afterdischarge. (3) A low current intensity of brief-pulse stimulation was more
      likely to terminate an afterdischarge.

PMID- 28761428
TI  - Monosialoganglioside 1 may alleviate neurotoxicity induced by propofol combined
      with remifentanil in neural stem cells.
AB  - Monosialoganglioside 1 (GM1) is the main ganglioside subtype and has
      neuroprotective properties in the central nervous system. In this study, we aimed
      to determine whether GM1 alleviates neurotoxicity induced by moderate and high
      concentrations of propofol combined with remifentanil in the immature central
      nervous system. Hippocampal neural stem cells were isolated from newborn Sprague
      Dawley rats and treated with remifentanil (5, 10, 20 ng/mL) and propofol (1.0,
      2.5, 5.0 MUg/mL), and/or GM1 (12.5, 25, 50 MUg/mL). GM1 reversed combined
      propofol and remifentanil-induced decreases in the percentage of 5
      bromodeoxyuridine(+) cells and also reversed the increase in apoptotic cell
      percentage during neural stem cell proliferation and differentiation. However,
      GM1 with combined propofol and remifentanil did not affect beta-tubulin(+) or
      glial fibrillary acidic protein(+) cell percentage during neural stem cell
      differentiation. In conclusion, we show that GM1 alleviates the damaging effects
      of propofol combined with remifentanil at moderate and high exposure
      concentrations in neural stem cells in vitro, and exerts protective effects on
      the immature central nervous system.

PMID- 28761430
TI  - Mechanisms underlying the promotion of functional recovery by deferoxamine after
      spinal cord injury in rats.
AB  - Deferoxamine, a clinically safe drug used for treating iron overload, also
      repairs spinal cord injury although the mechanism for this action remains
      unknown. Here, we determined whether deferoxamine was therapeutic in a rat model
      of spinal cord injury and explored potential mechanisms for this effect. Spinal
      cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra
      level. One group of injured rats received deferoxamine, a second injured group
      received saline, and a third group was sham operated. Both 2 days and 2 weeks
      after spinal cord injury, total iron ion levels and protein expression levels of
      the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta
      and the pro-apoptotic protein caspase-3 in the spinal cords of the injured
      deferoxamine-treated rats were significantly lower than those in the injured
      saline-treated group. The percentage of the area positive for glial fibrillary
      acidic protein immunoreactivity and the number of terminal deoxynucleotidyl
      transferase dUTP nick end labeling-positive cells were also significantly
      decreased both 2 days and 2 weeks post injury, while the number of NeuN-positive
      cells and the percentage of the area positive for the oligodendrocyte marker
      CNPase were increased in the injured deferoxamine-treated rats. At 14-56 days
      post injury, hind limb motor function in the deferoxamine-treated rats was
      superior to that in the saline-treated rats. These results suggest that
      deferoxamine decreases total iron ion, tumor necrosis factor-alpha, interleukin
      1beta, and caspase-3 expression levels after spinal cord injury and inhibits
      apoptosis and glial scar formation to promote motor function recovery.

PMID- 28761429
TI  - Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative
      stress-induced neuronal apoptosis.
AB  - Ganoderma lucidum polysaccharides have protective effects against apoptosis in
      neurons exposed to ischemia/reperfusion injury, but the mechanisms are unclear.
      The goal of this study was to investigate the underlying mechanisms of the
      effects of ganoderma lucidum polysaccharides against oxidative stress-induced
      neuronal apoptosis. Hydrogen peroxide (H2O2) was used to induce apoptosis in
      cultured cerebellar granule cells. In these cells, ganoderma lucidum
      polysaccharides remarkably suppressed H2O2-induced apoptosis, decreased
      expression of caspase-3, Bax and Bim and increased that of Bcl-2. These findings
      suggested that ganoderma lucidum polysaccharides regulate expression of apoptosis
      associated proteins, inhibit oxidative stress-induced neuronal apoptosis and,
      therefore, have significant neuroprotective effects.

PMID- 28761431
TI  - Synaptosomal-associated protein 25 may be an intervention target for improving
      sensory and locomotor functions after spinal cord contusion.
AB  - Synaptosomal-associated protein 25 kDa (SNAP-25) is localized on the synapse and
      participates in exocytosis and neurotransmitter release. Decreased expression of
      SNAP-25 is associated with Alzheimer's disease and attention
      deficit/hyperactivity disorder. However, the expression of SNAP-25 in spinal cord
      contusion injury is still unclear. We hypothesized that SNAP-25 is associated
      with sensory and locomotor functions after spinal cord injury. We established rat
      models of spinal cord contusion injury to detect gene changes with a gene array.
      A decreased level of SNAP-25 was detected by quantitative real time-polymerase
      chain reaction and western blot assay at 1, 3, 7, 14 and 28 days post injury.
      SNAP-25 was localized in the cytoplasm of neurons of the anterior and posterior
      horns, which are involved in locomotor and sensory functions. Our data suggest
      that reduced levels of SNAP-25 are associated with sensory and locomotor
      functions in rats with spinal cord contusion injury.

PMID- 28761432
TI  - Effects of pulsed radiofrequency on spasticity in patients with spinal cord
      injury: a report of two cases.
AB  - Spasticity following spinal cord injury (SCI) results in functional deterioration
      and reduced quality of life. Herein, we report two SCI patients who presented
      with good response to pulsed radiofrequency (PRF) for the management of
      spasticity in the lower extremities. Patient 1 (a 47-year-old man) had complete
      thoracic cord injury and showed a phasic spasticity on the extensor of both knees
      (3-4 beats clonus per every 30 seconds) and tonic spasticity (Modified Ashworth
      Scale: 3) on both hip adductors. Patient 2 (a 64-year-old man) had incomplete
      cervical cord injury and showed a right ankle clonus (approximately 20 beats)
      when he walked. After the application of PRF to both L2 and L3 dorsal root
      ganglion (DRG) (patient 1) and right S1 DRG (patient 2) with 5 Hz and 5 ms pulsed
      width for 360 seconds at 45V under the C-arm guide, all spasticity disappeared or
      was reduced. Moreover, the effects of PRF were sustained for approximately 6
      months with no side effects. We believe that PRF treatment can be useful for
      patients with spasticity after SCI.

PMID- 28761433
TI  - Mild closed head traumatic brain injury-induced changes in monoamine
      neurotransmitters in the trigeminal subnuclei of a rat model: mechanisms
      underlying orofacial allodynias and headache.
AB  - Our recent findings have demonstrated that rodent models of closed head traumatic
      brain injury exhibit comprehensive evidence of progressive and enduring orofacial
      allodynias, a hypersensitive pain response induced by non-painful stimulation.
      These allodynias, tested using thermal hyperalgesia, correlated with changes in
      several known pain signaling receptors and molecules along the trigeminal pain
      pathway, especially in the trigeminal nucleus caudalis. This study focused to
      extend our previous work to investigate the changes in monoamine neurotransmitter
      immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris
      and nucleus tractus solitaries following mild to moderate closed head traumatic
      brain injury, which are related to tactile allodynia, touch-pressure sensitivity,
      and visceral pain. Our results exhibited significant alterations in the
      excitatory monoamine, serotonin, in spinal trigeminal nucleus oralis and pars
      interpolaris which usually modulate tactile and mechanical sensitivity in
      addition to the thermal sensitivity. Moreover, we also detected a robust
      alteration in the expression of serotonin, and inhibitory molecule norepinephrine
      in the nucleus tractus solitaries, which might indicate the possibility of an
      alteration in visceral pain, and existence of other morbidities related to
      solitary nucleus dysfunction in this rodent model of mild to moderate closed head
      traumatic brain injury. Collectively, widespread changes in monoamine
      neurotransmitter may be related to orofacial allodynhias and headache after
      traumatic brain injury.

PMID- 28761434
TI  - Brain injury in combination with tacrolimus promotes the regeneration of injured
      peripheral nerves.
AB  - Both brain injury and tacrolimus have been reported to promote the regeneration
      of injured peripheral nerves. In this study, before transection of rat sciatic
      nerve, moderate brain contusion was (or was not) induced. After sciatic nerve
      injury, tacrolimus, an immunosuppressant, was (or was not) intraperitoneally
      administered. At 4, 8 and 12 weeks after surgery, Masson's trichrome, hematoxylin
      eosin, and toluidine blue staining results revealed that brain injury or
      tacrolimus alone or their combination alleviated gastrocnemius muscle atrophy and
      sciatic nerve fiber impairment on the experimental side, simultaneously improved
      sciatic nerve function, and increased gastrocnemius muscle wet weight on the
      experimental side. At 8 and 12 weeks after surgery, brain injury induction and/or
      tacrolimus treatment increased action potential amplitude in the sciatic nerve
      trunk. Horseradish peroxidase retrograde tracing revealed that the number of
      horseradish peroxidase-positive neurons in the anterior horn of the spinal cord
      was greatly increased. Brain injury in combination with tacrolimus exhibited
      better effects on repair of injured peripheral nerves than brain injury or
      tacrolimus alone. This result suggests that brain injury in combination with
      tacrolimus promotes repair of peripheral nerve injury.

PMID- 28761435
TI  - Critical signaling pathways during Wallerian degeneration of peripheral nerve.
AB  - Wallerian degeneration is a critical biological process that occurs in distal
      nerve stumps after nerve injury. To systematically investigate molecular changes
      underlying Wallerian degeneration, we used a rat sciatic nerve transection model
      to examine microarray analysis outcomes and investigate significantly involved
      Kyoto Enrichment of Genes and Genomes (KEGG) pathways in injured distal nerve
      stumps at 0, 0.5, 1, 6, 12, and 24 hours, 4 days, 1, 2, 3, and 4 weeks after
      peripheral nerve injury. Bioinformatic analysis showed that only one KEGG pathway
      (cytokine-cytokine receptor interaction) was significantly enriched at an early
      time point (1 hour post-sciatic nerve transection). At later time points, the
      number of enriched KEGG pathways initially increased and then decreased. Three
      KEGG pathways were studied in further detail: cytokine-cytokine receptor
      interaction, neuroactive ligand-receptor interaction, and axon guidance.
      Moreover, temporal expression patterns of representative differentially expressed
      genes in these KEGG pathways were validated by real time-polymerase chain
      reaction. Taken together, the above three signaling pathways are important after
      sciatic nerve injury, and may increase our understanding of the molecular
      mechanisms underlying Wallerian degeneration.

PMID- 28761437
TI  - Characterization of 2-Path Product Signed Graphs with Its Properties.
AB  - A signed graph is a simple graph where each edge receives a sign positive or
      negative. Such graphs are mainly used in social sciences where individuals
      represent vertices friendly relation between them as a positive edge and enmity
      as a negative edge. In signed graphs, we define these relationships (edges) as of
      friendship ("+" edge) or hostility ("-" edge). A 2-path product signed graph
      [Formula: see text] of a signed graph S is defined as follows: the vertex set is
      the same as S and two vertices are adjacent if and only if there exists a path of
      length two between them in S. The sign of an edge is the product of marks of
      vertices in S where the mark of vertex u in S is the product of signs of all
      edges incident to the vertex. In this paper, we give a characterization of 2-path
      product signed graphs. Also, some other properties such as sign-compatibility and
      canonically-sign-compatibility of 2-path product signed graphs are discussed
      along with isomorphism and switching equivalence of this signed graph with 2-path
      signed graph.

PMID- 28761436
TI  - Polyethylene glycol as a promising synthetic material for repair of spinal cord
      injury.
AB  - Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether.
      Owing to its good biological and material properties, polyethylene glycol shows
      promise in spinal cord tissue engineering applications. Although studies have
      examined repairing spinal cord injury with polyethylene glycol, these compelling
      findings have not been recently reviewed or evaluated as a whole. Thus, we herein
      review and summarize the findings of studies conducted both within and beyond
      China that have examined the repair of spinal cord injury using polyethylene
      glycol. The following summarizes the results of studies using polyethylene glycol
      alone as well as coupled with polymers or hydrogels: (1) polyethylene glycol as
      an adjustable biomolecule carrier resists nerve fiber degeneration, reduces the
      inflammatory response, inhibits vacuole and scar formation, and protects nerve
      membranes in the acute stage of spinal cord injury. (2) Polyethylene glycol
      coupled polymers not only promote angiogenesis but also carry drugs or bioactive
      molecules to the injury site. Because such polymers cross both the blood-spinal
      cord and blood-brain barriers, they have been widely used as drug carriers. (3)
      Polyethylene glycol hydrogels have been used as supporting substrates for the
      growth of stem cells after injury, inducing cell migration, proliferation, and
      differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce
      local glial scar invasion, promote and guide axonal regeneration, cross the
      transplanted area, and re-establish synaptic connections with target tissue,
      thereby promoting spinal cord repair. On the basis of the reviewed studies, we
      conclude that polyethylene glycol is a promising synthetic material for use in
      the repair of spinal cord injury.

PMID- 28761438
TI  - Differential Cloud Particles Evolution Algorithm Based on Data-Driven Mechanism
      for Applications of ANN.
AB  - Computational scientists have designed many useful algorithms by exploring a
      biological process or imitating natural evolution. These algorithms can be used
      to solve engineering optimization problems. Inspired by the change of matter
      state, we proposed a novel optimization algorithm called differential cloud
      particles evolution algorithm based on data-driven mechanism (CPDD). In the
      proposed algorithm, the optimization process is divided into two stages, namely,
      fluid stage and solid stage. The algorithm carries out the strategy of
      integrating global exploration with local exploitation in fluid stage.
      Furthermore, local exploitation is carried out mainly in solid stage. The quality
      of the solution and the efficiency of the search are influenced greatly by the
      control parameters. Therefore, the data-driven mechanism is designed for
      obtaining better control parameters to ensure good performance on numerical
      benchmark problems. In order to verify the effectiveness of CPDD, numerical
      experiments are carried out on all the CEC2014 contest benchmark functions.
      Finally, two application problems of artificial neural network are examined. The
      experimental results show that CPDD is competitive with respect to other eight
      state-of-the-art intelligent optimization algorithms.

PMID- 28761440
TI  - Fuzzy Classification of High Resolution Remote Sensing Scenes Using Visual
      Attention Features.
AB  - In recent years the spatial resolutions of remote sensing images have been
      improved greatly. However, a higher spatial resolution image does not always lead
      to a better result of automatic scene classification. Visual attention is an
      important characteristic of the human visual system, which can effectively help
      to classify remote sensing scenes. In this study, a novel visual attention
      feature extraction algorithm was proposed, which extracted visual attention
      features through a multiscale process. And a fuzzy classification method using
      visual attention features (FC-VAF) was developed to perform high resolution
      remote sensing scene classification. FC-VAF was evaluated by using remote sensing
      scenes from widely used high resolution remote sensing images, including IKONOS,
      QuickBird, and ZY-3 images. FC-VAF achieved more accurate classification results
      than the others according to the quantitative accuracy evaluation indices. We
      also discussed the role and impacts of different decomposition levels and
      different wavelets on the classification accuracy. FC-VAF improves the accuracy
      of high resolution scene classification and therefore advances the research of
      digital image analysis and the applications of high resolution remote sensing
      images.

PMID- 28761439
TI  - Extracting T-S Fuzzy Models Using the Cuckoo Search Algorithm.
AB  - A new method called cuckoo search (CS) is used to extract and learn the Takagi
      Sugeno (T-S) fuzzy model. In the proposed method, the particle or cuckoo of CS is
      formed by the structure of rules in terms of number and selected rules, the
      antecedent, and consequent parameters of the T-S fuzzy model. These parameters
      are learned simultaneously. The optimized T-S fuzzy model is validated by using
      three examples: the first a nonlinear plant modelling problem, the second a Box
      Jenkins nonlinear system identification problem, and the third identification of
      nonlinear system, comparing the obtained results with other existing results of
      other methods. The proposed CS method gives an optimal T-S fuzzy model with fewer
      numbers of rules.

PMID- 28761441
TI  - Association between HLA-DQ Gene Polymorphisms and HBV-Related Hepatocellular
      Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related
      mortality worldwide. Host gene variants may influence hepatitis B virus- (HBV-)
      related HCC. Human leukocyte antigens (HLA) play an important role in presenting
      virus antigens to immune cells that are responsible for the clearance of virus
      infected cells and tumor cells. Previous studies have investigated the HLA-DQ
      (rs2856718 and rs9275572) polymorphisms that may be associated with the
      development of HBV-related HCC. However, the results are controversial or
      inconclusive. Hence, we conducted a meta-analysis to derive a more precise
      estimation of the associations. A total of 6 articles were used to evaluate the
      effect of the two polymorphisms on the risk of HBV-related HCC. Odds ratios (ORs)
      and 95% confidence intervals (95% CIs) were calculated. We found that rs2856718
      and rs9275572 in HLA-DQ significantly decreased HBV-related HCC in total
      population, especially in Chinese, but not in Saudi Arabian. Further validation
      of our results in larger populations and different ethnicities are required.

PMID- 28761442
TI  - Effects of Exercise Training on Fat Loss and Lean Mass Gain in Mexican-American
      and Korean Premenopausal Women.
AB  - We investigated the effect of exercise training on body composition change in
      women. Nineteen Mexican-American and 18 Korean premenopausal overweight/obese
      women were randomized into one of the following groups: control, low-intensity
      training group (LI), and high-intensity training group (HI). Subjects completed
      12 weeks of training at 50-56% maximal oxygen consumption (LI) or 65-70% maximal
      oxygen consumption (HI). Body composition components were measured at baseline
      and after training using dual-energy X-ray absorptiometry for Mexican-Americans,
      while whole-body composition was measured by the direct segmental multifrequency
      bioelectrical impedance analysis and abdominal fat was measured by single-slice
      computed tomography for Koreans. Data were analyzed using mixed-model repeated
      measures independent of age, ethnicity, and body mass index (BMI). Exercise
      training showed a significant effect on BMI, fat percentage, fat mass, lean mass,
      and visceral adipose tissue area. HI significantly decreased fat mass and fat
      percentage but increased lean mass (all P < 0.05). LI significantly reduced BMI,
      fat mass, fat percentage, and visceral adipose tissue area but increased lean
      mass (all P < 0.05). Exercise training had a beneficial effect on reducing BMI,
      fat percentage, fat mass, and visceral adipose tissue area but had no effect on
      increasing lean mass for Mexican-American and Korean premenopausal
      overweight/obese women.

PMID- 28761444
TI  - Seronegative Autoimmune Hepatitis A Clinically Challenging Difficult Diagnosis.
AB  - Autoimmune hepatitis (AIH) is a complex liver disease of unknown cause which
      results in immune-mediated liver injury with varied clinical presentations.
      Seronegative AIH follows a similar course to autoantibody-positive disease and
      diagnosis may be challenging. There are no single serologic tests of sufficient
      diagnostic specificity, and delay in appropriate treatment may lead to
      progression of the liver disease and liver failure. The revised conventional
      diagnostic criteria (RDC) scoring for AIH is complex and not routinely used in
      the clinical practice. The more recent simplified diagnostic criteria (SDC)
      scoring proposed by International Autoimmune Hepatitis Group in 2008 has wider
      application in routine practice facilitating the diagnosis of AIH with a
      specificity and sensitivity of ~90%. In this report, we describe a case of
      seronegative autoimmune hepatitis diagnosed using RDC. SDC score calculated in
      our case was 4 and was not diagnostic for AIH. We subsequently used the complex
      revised diagnostic criteria for definitive diagnosis. Some of the patients
      previously diagnosed as cryptogenic active hepatitis of unknown etiology probably
      had an unrecognized diagnosis of seronegative autoimmune hepatitis. SDC scoring
      may not be applicable in patients with seronegative autoimmune hepatitis. These
      patients should be reassessed by using RDC.

PMID- 28761443
TI  - Relying on Visiting Foreign Doctors for Fistula Repair: The Profile of Women
      Attending Fistula Repair Surgery in Somalia.
AB  - Obstetric fistula is treatable by surgery, although access is usually limited,
      particularly in the context of conflict. This study examines the profile of women
      attending fistula repair surgery in three hospitals in Somalia. A cross-sectional
      study was conducted in Somalia from August to September 2016. Structured
      questionnaires were administered to 81 women who registered for fistula repair
      surgery in the Garowe, Daynile, and Kismayo General Hospitals in Somalia.
      Findings revealed that 70.4% of the study participants reported obstetric labor
      as the cause of their fistula, and 29.6% reported iatrogenic causes. Regarding
      the waiting time for the repair surgery, 45% waited for the surgery for over one
      year, while the rest received the surgery within a year. The study suggests that
      training for fistula surgery has to be provided for healthcare professionals in
      Somalia, fistula centers should be established, and access to these facilities
      has to be guaranteed for all patients who need these services.

PMID- 28761445
TI  - In Vitro and In Vivo Dentinogenic Efficacy of Human Dental Pulp-Derived Cells
      Induced by Demineralized Dentin Matrix and HA-TCP.
AB  - Human dental pulp cells have been known to have the stem cell features such as
      self-renewal and multipotency. These cells are differentiated into hard tissue by
      addition of proper cytokines and biomaterials. Hydroxyapatite-tricalcium
      phosphates (HA-TCPs) are essential components of hard tissue and generally used
      as a biocompatible material in tissue engineering of bone. Demineralized dentin
      matrix (DDM) has been reported to increase efficiency of bone induction. We
      compared the efficiencies of osteogenic differentiation and in vivo bone
      formation of HA-TCP and DDM on human dental pulp stem cells (hDPSCs). DDM
      contains inorganic components as with HA-TCP, and organic components such as
      collagen type-1. Due to these components, osteoinduction potential of DDM on
      hDPSCs was remarkably higher than that of HA-TCP. However, the efficiencies of in
      vivo bone formation are similar in HA-TCP and DDM. Although osteogenic gene
      expression and bone formation in immunocompromised nude mice were similar levels
      in both cases, dentinogenic gene expression level was slightly higher in DDM
      transplantation than in HA-TCP. All these results suggested that in vivo
      osteogenic potentials in hDPSCs are induced with both HA-TCP and DDM by
      osteoconduction and osteoinduction, respectively. In addition, transplantation of
      hDPSCs/DDM might be more effective for differentiation into dentin.

PMID- 28761446
TI  - Characteristics of Human Endometrium-Derived Mesenchymal Stem Cells and Their
      Tropism to Endometriosis.
AB  - Human endometrial tissue has become an attractive source of mesenchymal stem
      cells (MSCs) for cell-based therapies because these MSCs can be easily harvested
      and have tumour tropism as well as reduced immunogenic and inflammatory
      properties. Our study aimed to obtain and characterise human endometrial
      mesenchymal stem cells (EMSCs) and assess their endometriosis tropism. EMSCs were
      successfully isolated from the endometrium of women undergoing laparoscopy for
      idiopathic infertility. The EMSCs presented a fibroblast-like morphology during
      culture. Flow cytometry analyses showed that the cells were positive for the
      specific stem cell markers CD73, CD90, CD105, CD166, and HLA-ABC (major
      histocompatibility complex class I (MHC I)) but negative for CD14, CD34, CD45,
      and HLA-DR (MHC II). Reverse transcription polymerase chain reaction results
      showed that the EMSCs expressed the stem cell marker OCT4. The EMSCs could
      differentiate into osteocytes, adipocytes, and chondrocytes under certain
      conditions. The EMSCs had a high tropism to endometriosis without
      tumourigenicity. This study enhances the possibility of using EMSCs as drug
      carriers in human cell-based therapies. Meanwhile, future research could also
      focus on developing targeted therapies for endometriosis.

PMID- 28761447
TI  - Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells:
      A New Insight into the Role of ICAM-1.
AB  - Mesenchymal stromal cells (MSC) control excessive inflammation and create a
      microenvironment for tissue repair protecting from chronic inflammation and
      tissue fibrosis. We examined the molecular mechanisms of MSC immunomodulatory
      function in mixed cultures of human adipose-derived MSC with lymphocytes. Our
      data show that MSC promote unstimulated lymphocyte survival potentially by an
      increase in antigen presentation. Under inflammatory conditions, mimicked by
      stimulation of TCR in lymphocytes, MSC suppress activation and proliferation of
      stimulated T cells. Immunosuppression is accompanied by downregulation of IL
      2Ralpha that negatively affects the survival of activated T cells. MSC upregulate
      transcription of indolamine-2,3-dioxygenase (IDO) and inducible NO synthase
      (iNOS), which generate products negatively affecting T cell function. Both MSC
      and lymphocytes dramatically increase the surface ICAM-1 level in mixed cultures.
      Antibody-mediated blockage of surface ICAM-1 partially releases MSC-mediated
      immune suppression in vitro. Our data suggest that MSC have cell-intrinsic
      molecular programs depending on the inflammatory microenvironment. We speculate
      that MSC sense soluble factors and respond by surface ICAM-1 upregulation. ICAM-1
      is involved in the control of T cell activation leading to immunosuppression or
      modest stimulation depending on the T cell status. Immunomodulation by MSC
      ranging from support of naive T cell survival to immunosuppression of activated T
      cells may affect the tissue microenvironment protecting from aberrant
      regeneration.

PMID- 28761448
TI  - Relationship of sodium intake with obesity among Iranian children and
      adolescents.
AB  - BACKGROUND: Emerging evidence suggests a relationship between sodium (Na) intake
      and obesity risk. The aim of this study was to investigate the link between 24
      hour (24-h) urinary Na excretion and adiposity measures in a sample of Iranian
      children and adolescents. METHODS: This cross-sectional study was performed among
      374 healthy individuals aged 11-18 years old. Random cluster sampling method was
      used to select the participants from 4 districts in Isfahan, Iran. Na excretion
      was estimated using a 24-h urinary sample. Creatinine (Cr) level was used to
      confirm the completeness of samples. Anthropometric measures including weight,
      height and waist circumference (WC) were obtained based on standard protocols.
      RESULTS: The odds ratio (OR) for overweight/obesity in subjects with the highest
      tertile of Na excretion compared with the lowest tertile was 8.01 [95% confidence
      interval (CI) 4.20-15.3] in crude model and 8.33 (95% CI 4.14-16.8) after
      adjusting for potential confounders. The association was independent of intake of
      energy and sugar-sweetened beverages (SSBs). The OR for abdominal obesity in the
      highest tertile of Na excretion compared with the lowest tertile was 9.12 (95% CI
      4.78- 17.4) in crude model and 9.75 (95% CI 4.88-19.5) after controlling for
      potential confounders. The association was independent of energy intake or SSBs
      consumption. CONCLUSION: Our study showed a positive association between Na
      excretion and obesity among children and adolescents. Further investigation
      through longitudinal studies using a more representative sample of children and
      adolescents is suggested to determine whether this is a causal relationship.

PMID- 28761449
TI  - Dietary approaches to stop hypertension diet and obesity: A cross-sectional study
      of Iranian children and adolescents.
AB  - BACKGROUND: Few studies have investigated the effects of dietary approaches to
      stop hypertension (DASH) diet on obesity in children. The present study was
      conducted to examine adherence to the DASH diet in relation to obesity in
      children and adolescents, Isfahan, Iran. METHODS: A cross-sectional study was
      carried out among 456 children aged 11-18 years who were selected by random
      cluster sampling method. Dietary intakes were assessed using a validated Food
      Frequency Questionnaire (FFQ). The DASH score was constructed based on food items
      emphasized or minimized in the DASH diet. Anthropometric measurements were
      conducted based on standard protocols. General and abdominal obesity were defined
      based on body mass index >= 95th percentiles and waist: height ratio of more than
      0.5, respectively. RESULTS: Higher adherence to DASH diet was inversely
      associated with general obesity (odds ratioT1 vs. T3 3.34, 95% confidence
      interval 1.28-8.75); however, after controlling for confounding factors, this
      association disappeared. Furthermore, higher adherence to DASH diet was
      negatively associated with central obesity in children, but the relation was not
      statistically significant. CONCLUSION: We concluded that there was an inverse
      nonsignificant association between adherence to DASH diet and general obesity
      indices after adjustment for potential confounders. Further, well-designed
      randomized clinical trial studies are suggested to find out the effect of DASH
      diet on obesity obviously.

PMID- 28761450
TI  - Lipidemic effects of common edible oils and risk of atherosclerosis in diabetic
      Wistar rats.
AB  - BACKGROUND: Diabetic state potentiates atherosclerosis and the type of edible oil
      consumed by the individual may affect this further. This study aimed to determine
      if the common edible oils in Nigeria have any effects on the lipid profiles and
      arteries of alloxan-induced diabetic male Wistar rats. METHODS: Thirty male
      Wistar rats were randomly divided into five groups of normal control, diabetic
      control, animals on diet enriched with refined, bleached deodorized palm oil (RBD
      PO), animals on diet enriched with soya oil, and animals on diet enriched with
      olive oil. At the end of 8 weeks, the lipid profiles of the animals were
      determined before sacrificing them. Their aortas were subsequently harvested for
      histological examination. RESULTS: The olive oil fed group had the highest level
      of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C),
      lowest HDL-C, and highest artherogenic index (AI). Diabetic animals fed on RBD-PO
      had a lower non-HDL-C, higher HDL-C, and lower AI than diabetic animals fed on
      olive oil or soya oil. However, the diabetic animals fed on RBD-PO had the
      highest triglyceride level. When the aortas were examined histologically, there
      were no atherosclerotic lesions in all the control and experimental groups except
      those fed on 10% soya oil enriched diet that had type II atherosclerotic lesions
      according to American Heart Association (AHA). CONCLUSION: The result of our
      study showed that RBD-PO appears to offer a better lipid profile in the diabetic
      animals compared with olive oil and soya oil. Soya oil appears to cause the
      development of atherosclerosis in diabetic state.

PMID- 28761451
TI  - The impact of educational intervention on self-care behaviors in overweight
      hypertensive women: A randomized control trial.
AB  - BACKGROUND: The improper control of self-care in hypertension imposes a lot of
      financial burden on the health-care system. On the other hand, the importance of
      participatory care and high effectiveness of self-management programs have been
      confirmed. This study was aimed to examine the effect of an educational
      intervention on self-efficacy, self-care behaviors and blood pressure (BP) of
      hypertensive obese or overweight women in the primary health-care setting in
      Isfahan, Iran. METHODS: This randomized controlled trial was an educational
      intervention program. It was performed among 146 hypertensive women of 30-65 age
      range who referred to 6 health care centers of Isfahan that randomly assigned to
      a control and intervention groups. The interventional group participated in the 6
      weekly sessions including exercises, weight control, medication adherence, and
      home self-monitoring based on goal setting, and promotion of self-efficacy. The
      control group received routine care from health-care center and any special
      intervention has been done for the control group. Output variables were analyzed
      after intervention, and 6-month follow-up. RESULTS: There are no significant
      differences between age, weight, body mass index and BP and biochemical variables
      except lipids as well as behavioral factors at the baseline. After 6 months
      intervention self-efficacy (< 0.001) and physical activity (< 0.001) improvement
      of in the intervention group was significantly different in comparison with the
      control group. After 6 months, there was a significant reduction in systolic (P <
      0.001) and diastolic BP (P = 0.010) in the intervention group. CONCLUSION:
      Participatory method of education could help us to convince patients to have
      better self-care to control disease. Furthermore, since adherence to the
      treatment of hypertensive patients in our society is low, organizing such courses
      can teach essential knowledge and skills to lifestyle change and prevention of
      complications. Performing these courses is recommended for other chronic disease
      patients in health-care centers to assess self-management programs on self-care
      behavior.

PMID- 28761452
TI  - Comparison of manual versus automated blood pressure measurement in intensive
      care unit, coronary care unit, and emergency room.
AB  - BACKGROUND: Accuracy of blood pressure (BP) measurement in clinical settings is
      one of the most concerns despite of promotion in techniques for the measurement
      of BP. Our aim was to compare automated versus manual BP measurement in intensive
      care unit (ICU), coronary care unit (CCU), and emergency room patients. METHODS:
      Totally, 117 patients in ICU, CCU, and emergency department were registered in
      the study. Demographic information was recorded. The cardioset heart monitoring
      device was used for measuring BP and mercury sphygmomanometer with appropriate
      cuffs was used for manual method. Then, the mean BP of two methods was compared
      based on different age, sex, weight, and disease findings. RESULTS: The mean
      systolic blood pressure (SBP) was 124.526 mmHg, with minimum and maximum of
      123.111 and 125.940 mmHg, respectively (Cronbach's alpha = 0.893); furthermore,
      mean diastolic blood pressure (DBP) was 73.496 mmHg, with minimum and maximum of
      72.718 and 74.247 mmHg, respectively (Cronbach's alpha = 0.852). SBP was
      significantly different between the two methods, and especially in patients below
      60 years, hospitalized in ICU ward, overweight, mid-upper arm circumference below
      27 cm, and with neurosurgery problems, it was higher by manual method (P <
      0.050). Moreover, DBP was more in manual method in patients with female sex,
      below 60 years, hospitalized in ICU ward and with neurosurgery problems (P <
      0.050). CONCLUSION: The results of this study suggested that manual method in
      measurement of BP frequently shows higher BP, especially in patients admitted to
      hospitals-affecting up to 15 mmHg higher, and this discrepancy is more in
      critical situations.

PMID- 28761453
TI  - The prevalence of obesity among school-aged children and youth aged 6-18 years in
      Iran: A systematic review and meta-analysis study.
AB  - BACKGROUND: Obesity is considered as a major health problem of children and
      adolescents. The present meta-analysis was conducted by extensive search of
      studies on the prevalence of obesity among school-aged children and youth aged 6
      18 years in Iran. METHODS: All conducted cross-sectional studies on the
      prevalence of obesity in Iranian students in all grades were extracted, without
      applying any restriction on time in national and international databases
      including Magiran, Iranmedex, SID, Scopus, Google Scholar, and PubMed.
      Statistical software Stata 12 was used to analyze the data and to obtain the
      prevalence of obesity among Iranian students. The heterogeneity between the
      results was determined using statistical test I2. RESULTS: In this meta-analysis,
      51 papers met our inclusion criteria and were therefore considered for the
      analysis. The prevalence of obesity was equal to 5.82% [95% confidence interval
      (CI): 5-6.66] in Iranian students. The prevalence of obesity was higher in boys
      than in girls (6.85% compared to 5.13%) (P = 0.300). The highest prevalence of
      obesity was related to students living in the North and Northwest areas with
      7.07% (95% CI: 4.35-9.78). CONCLUSION: The prevalence of obesity among Iranian
      students is not high when compared to Western countries. However, due to
      lifestyle changes in recent years, it is necessary to plan intervention programs
      within families and schools to improve dietary patterns and physical activity of
      this age group.

PMID- 28761454
TI  - Meticulous observations essential before and after coil embolization of pulmonary
      arteriovenous malformation; lessons learned from two case.
AB  - BACKGROUND: Endovascular coil embolization is an approved treatment for pulmonary
      arteriovenous malformation (AVM) but it brings high rate of thromboembolic
      complications with subsequent morbidity and mortality. Hereby, we report two
      cases of AVM coil embolization and management of their compilations. CASE REPORT:
      The first case was a 57-year-old male with five implanted coils in the lower lobe
      of right lung in which two of them were migrated soon after implantation. On
      exploration, a large atrial septal defect was detected and then repaired
      successfully. The next day, he was transferred for fluoroscopy. Two embolized
      coils were found at the site of the left iliac artery which was extracted via
      snare through sheath implanted in the left femoral artery. Coil migration to the
      left atrium and subsequently to the left iliac artery is reported for the first
      time. The second case was a 45-year-old male with central cyanosis and clubbing
      of upper and lower extremities from childhood. On computed tomography angiography
      (CTA), a vascular lesion was found. The patient underwent coil embolization for
      closure of AVM. The patient was still symptomatic after successful closure of
      AVM. On CTA, two feeding arteries were detected. He underwent second coil
      embolization procedure. CONCLUSION: AVM coil embolization is a temptative
      procedure, which should be performed on its real indications by an expert centers
      who can handle complications of this procedure. The performance of CTA seems
      beneficial in some cases to confirm complete embolization of AVM.

PMID- 28761455
TI  - Unusual presentation of extensive spontaneous coronary dissection: Case report
      and literature review.
AB  - BACKGROUND: The etiology of spontaneous dissection of coronary artery (SDCA) is
      not well understood yet. Different studies have linked this entity to pregnancy,
      physical stress, collagen diseases and vasculitis. In general, patients do not
      exhibit the classic risk factors for coronary artery disease, which mandates the
      suspicion of this condition, especially in young adults with acute coronary
      syndrome. CASE REPORT: In this article, we report the case of a 63-year old male
      patient, asymptomatic, who came for periodic evaluation and after evaluation by
      exercise and myocardial scintigraphy had high suspicion for severe coronary
      artery disease and underwent coronary angiography, which showed spontaneous
      dissection of the left and right branches of the coronary arteries. CONCLUSION:
      The choice of therapeutic strategies (clinics, percutaneous or surgical) remains
      uncertain and should be individualized by the features and form of presentation
      of the SDCA.

PMID- 28761457
TI  - In Vitro Assay of Paecilomyces lilacinus Biocontrol Effects on Fasciola hepatica
      Eggs Illustrated in Scanning Electron Micrographs.
AB  - BACKGROUND: Fascioliasis is a zoonotic disease caused by the liver fluke Fasciola
      hepatica. Drug resistance, high costs of treatment and economic losses in meat
      production have emerged the need of alternative control measures into
      consideration. The aim of this study was to evaluate the in vitro ovicidal
      activity of Paecilomyces lilacinus fungus on F. hepatica eggs. METHODS: P.
      lilacinus isolated from the soil of natural environment was challenged on F.
      hepatica eggs to observe the bio control effect of nematophagous fungi on
      trematode helminth eggs. The study was conducted in Tehran University of Medical
      Sciences, in 2015. Within 21 d of experiment, destructive effects exhibited on
      the eggshells were investigated using optical and Scanning Electron Microscopy.
      RESULTS: The effective role of P. lilacinus on damaging the eggs of F. hepatica
      was noticed. CONCLUSION: This finding is promising for advantageous use of
      nematophagus fungi as a natural constituent in hyper endemic areas for certain
      helminthic infections like fascioliasis with diverse kinds of herbivores as egg
      passer hosts.

PMID- 28761456
TI  - Visceral Leishmaniasis in Southeastern Iran: A Narrative Review.
AB  - BACKGROUND: Visceral leishmaniasis (VL) has strong links with poverty,
      substantial medical and veterinary impacts. This review aimed to focus in studies
      published during 1994-2016 on VL in southeastern Iran. METHODS: The present
      review is based on expert knowledge and historical studies published during the
      past 23 yr (1994-2016) on VL in southeastern Iran. In addition, related
      literature found in PubMed by using the keywords such as visceral leishmaniasis,
      kala-azar, and Leishmania infantum are included. RESULTS: Overall, 118 children
      aged 4.2 yr were detected as infected with human VL (HVL). The majority of the
      cases were from Orzoieh district (37.1%) in southwest of Kerman Province,
      followed by Sirjan (15.7%), Jiroft (14.8%), Kahnuj (9.3%) and to lesser extent
      from other areas. The male to female ratio was 1.7. The three most frequent
      clinical features were represented by fever (100.0%), anemia (95.0%) and
      splenomegaly (91.5%). Altogether, 42.0% of the VL cases developed secondary
      bacterial infections, the overall case-fatality rate was 3.4%, and majorities
      (88.0%) of the VL patients were undernourished. Overall, 733 dogs and wild
      canines were examined by different techniques with various seroprevalence ranges.
      CONCLUSION: In southeastern Iran, VL is endemic in Orzoieh district in Kerman
      Province. While the dogs are implicated as the main domestic reservoir of VL,
      wide range of wild canines can serve as a secondary potential reservoir host.

PMID- 28761458
TI  - Genotyping, Drug Susceptibility and Prevalence Survey of Trichomonas vaginalis
      among Women Attending Gynecology Clinics in Hamadan, Western Iran, in 2014-2015.
AB  - BACKGROUND: In spite of sufficient knowledge about phenotypic variation of
      Trichomonas vaginalis, its genetic characteristics are poorly understood. We
      carried out a molecular epidemiology study in which in vitro metronidazole
      susceptibility of T. vaginalis isolates was considered. METHODS: This study was
      conducted on 862 women admitted to Gynecology Clinics in Hamadan, west of Iran,
      during 2014-2015. After recording the socio-demographic and clinical
      characteristics of participants, vaginal swab samples were taken and subjected to
      microscopic examination, culture, in vitro sensitivity testing and PCR
      restriction fragment length polymorphism (RFLP) analysis. RESULTS: T. vaginalis
      was detected in 1.9% (16/862) of the samples using two parasitological methods.
      The all T. vaginalis isolates that subjected to drug susceptibility analysis were
      sensitive to metronidazole with MICs ranged from 0.4 to 12.8 MUg/ml. T. vaginalis
      genotyping by using actin gene and PCR-RFLP analysis identified three actin type;
      A (9, 56%), I (6, 38%) and E (1, 6%). No significant correlation was observed
      between actin genotypes and their clinical manifestation (P>0.05). CONCLUSION:
      The prevalence of T. vaginalis infection is not noticeable in the region and the
      most of isolates are hypersensitive to metronidazole. Further studies are needed
      to clarify the efficiency of the actin gene, as a reliable genetic marker, for
      molecular epidemiology of trichomoniasis.

PMID- 28761459
TI  - Molecular Detection and Genotyping of Toxoplasma gondii in Chicken, Beef, and
      Lamb Meat Consumed in Northwestern Iran.
AB  - BACKGROUND: Toxoplasma gondii, the obligate, intracellular parasite afflicts
      human in diverse ways such as ingestion of tissue cysts in undercooked meat. The
      aim of this study was to assess the prevalence and genotyping of Toxoplasma
      isolated from meat samples being consumed in East Azerbaijan, Northwest of Iran.
      METHODS: Overall, 150 samples including chicken, beef and lamb meat were
      collected from retailers in different regions of Tabriz, northwestern Iran during
      April to September 2014. Molecular detection was done by amplifying B1 gene and
      T. gondii surface antigen 2 (SAG2) loci. For genotyping of T. gondii, restriction
      fragment length polymorphism (RFLP) was performed using Sau3AI and HhaI
      restriction enzymes. Finally, three positive isolate from each host was sequenced
      to evaluate and phylogenetic analysis. RESULTS: Overall, 26 (17.33%) samples were
      positive for T. gondii including 4 (8%) isolate from chicken, 8 (16%) isolates
      from cattle and 14 (28%) isolates from sheep. According to the RFLP patterns,
      sequencing and phylogenetic results, all of the samples were identified as
      genotype I. CONCLUSION: The results indicated a potential risk of transmission of
      the disease through the consumption of infected meat. This is particularly
      important especially for pregnant women and immuno-compromised patients and this
      suggests that the training on the prevention of infection is necessary.

PMID- 28761460
TI  - Relationships between Oxidative Stress, Liver, and Erythrocyte Injury, Trace
      Elements and Parasite Burden in Sheep Naturally Infected with Dicrocoelium
      dendriticum.
AB  - BACKGROUND: The aim of this study was to investigate the role of oxidative stress
      in the pathology of ovine dicrocoeliasis. METHODS: During Dec 2013 - Oct 2014,
      seventy-two sheep (1-3 years) with liver dicrocoeliasis along with 47 healthy
      sheep were selected from animals admitted for slaughtering at slaughterhouse
      located in Neyshabour, Razavi Khorasan Province, Iran. RESULTS: In comparison to
      healthy control, the malondialdehyde (MDA) level and serum total antioxidant
      capacity were significantly higher in the parasitized group (P<0.05). A
      significant increase in liver MDA concentration (P<0.05) of parasitized group was
      also observed. Packed cell volume (PCV), zinc, iron, total bilirubin and albumin
      sera levels were significantly lower in the parasitized group (P<0.05). In
      parasitized sheep, a significant positive correlation was seen between serum MDA
      concentration and the activity of aspartate aminotransferase (AST). On the other
      hand, the concentration of serum MDA was inversely correlated with the value of
      PCV. No significant differences were observed for MDA concentration and total
      antioxidant capacity between normal and abnormal hepatic lobes in the parasitized
      animals. Oxidative stress markers (MDA and total antioxidant capacity in serum
      and liver samples) showed no significant correlations with the extent of
      pathological lesions and serum variables of liver injury in the parasitized
      sheep. No significant correlation was observed between oxidative stress markers
      and the fluke's number in the parasitized animals. CONCLUSION: Oxidative stress
      may play an important role in the erythrocyte destruction in sheep naturally
      infected with D. dendriticum. However, no clear relationships were observed
      between the oxidative stress, hepatic damage and parasite burden.

PMID- 28761461
TI  - PCR-based Diagnosis of Toxoplasma Parasite in Ocular Infections Having Clinical
      Indications of Toxoplasmosis.
AB  - BACKGROUND: The diagnosis of ocular toxoplasmosis is mainly based on clinical
      features. However, ocular fluid testing by PCR may be very helpful for approval
      or rejection of this etiology. In this study, we utilized a nested-PCR technique,
      targeting the B1 partial sequence to analyze the aqueous and vitreous samples for
      evaluating the presence of the Toxoplasma DNA. METHODS: Fifty aqueous or vitreous
      humor samples were obtained from patients with clinical features of ocular
      toxoplasmosis admitted to ophthalmology hospitals and clinics in Iran, within
      2014. The samples were subsequently subjected to DNA extraction and purification.
      For nested amplification of the Toxoplasma B1 gene, two primer pairs were used.
      The outer and inner primers are expected to produce a 193 bp and a 96 bp
      fragments, respectively. RESULTS: The first-round PCR resulted in the detection
      of T. gondii in 58% of samples by amplification of the expected 193bp DNA
      fragment. The nested-PCR using the inner primers, detected 15 additional samples
      from those with negative amplicons in the first round PCR (overall positivity of
      88%). In addition, vitreous samples showed relatively more positive cases than
      aqueous humor in detection of the infection. CONCLUSION: The nested-PCR protocol
      using the B1 gene, with the high detection power, could be a useful complimentary
      method to clinical diagnose of ocular toxoplasmosis.

PMID- 28761463
TI  - The 33.1 kDa Excretory/secretory Protein Produced by Toxocara canis Larvae Serves
      as a Potential Common Biomarker for Serodiagnosis of Toxocariasis in Paratenic
      Animals and Human.
AB  - BACKGROUND: Toxocariasis is a prevalent zoonosis disease caused by the closely
      related nematode species Toxocara canis and Toxocara cati which parasitise
      Canidae and Felidae respectively. In paratenic hosts, larvae of these worms cause
      multiple organ damage. However, how these paratenic hosts response to these worms
      and whether any common biomarker can be applied for diagnosis are still unclear.
      METHODS: Excreted/secreted (E/S) antigens were prepared by culture of T. canis
      larvae in vitro. Using a western blot (WB) assay the humoral IgG responses,
      induced by Toxocara spp. larvae to the worm's E/S antigens in different infected
      hosts including mice, rabbits and human, were examined. RESULTS: In a mouse model
      of toxocariasis, intraperitoneal injection of T. canis larvae induces
      inflammatory leukocyte accumulation in the liver and the lungs but not in the
      brain, although a remarkable number of larvae were detected in this organ. Mice
      and rabbits responded differently to Toxocara spp. resulting in distinct
      heterogenous WB band patterns. Mice and rabbits both responded to a 33.1 kDa E/S
      constituent that turned out to be the most sensitive protein for serodiagnosis.
      Sera from human toxocariasis patients showed heterogenous WB band patterns
      similar to those observed in rabbits and all responded to the 33.1 kDa band.
      CONCLUSION: 33.1 kDa E/S protein can be considered as a critical common biomarker
      for toxocariasis immuno-diagnosis in both paratenic animals and human and its
      specificity requires further investigation.

PMID- 28761462
TI  - Subtypes Distribution and Frequency of Blastocystis sp. Isolated from Diarrheic
      and Non-diarrheic Patients.
AB  - BACKGROUND: Blastocystis is one of the most common parasites, reported from both
      human and animals. This parasite is more prevalent in regions with low levels of
      hygiene, close contact with animal and unsuitable disposal systems. The aim of
      the study was to subtype Blastocystis sp., isolated from diarrheic and non
      diarrheic patients using sequencing of 18S ribosomal DNA. METHODS: Totally, 300
      stool samples were collected from diarrheic and nondiarrheic patients referred to
      Imam Reza Hospital, Tehran from Apr to Aug 2015. All samples were concentrated
      using conventional Formalin - ether technique and recognized under light
      microscope. The fresh stool samples were also cultivated in clotted fetal bovine
      medium and examined for growing of Blastocystis every 48 h with direct smear
      slides for 10 d. DNA extraction was performed on all positive samples. Amplified
      DNA fragment of 18S rDNA was sequenced and compared with reference genes,
      previously deposited in Genbank database. RESULTS: The number of diarrheic and
      non-diarrheic patients participated in the study was 134 (44.66%) and 166
      (55.34%), respectively. Three subtypes 1, 2, 3 were identified from positive
      samples. Subtype 2 was the most prevalent (36.5%) followed by subtype 1 (33.3%)
      and subtype 3 (30.2%). There were no mixed subtypes. Furthermore, the most
      prevalent subtypes in diarrheic and non-diarrheic patients were subtype 2
      (39.28%) and subtype 1 (37.14%), respectively. CONCLUSION: Blastocystis sp., is
      one of the most prevalent unicellular parasites among diarrheic and non-diarrheic
      patients. Indeed, ST2 was the most prevalent subtype particularly in those
      samples collected from diarrheic patients.

PMID- 28761464
TI  - Genetic Variation of Giardia lamblia Isolates from Food-handlers in Kashan,
      Central Iran.
AB  - BACKGROUND: Based on genotyping study of human isolates of Giardia lamblia;
      humans are mainly infected by two assemblages A and B. The present study was
      carried out to determine the sub-assemblages of G. lamblia isolated from food
      handlers referred to Kashan health centers, central Iran, 2015. METHODS: In this
      cross-sectional study, 3653 stool samples collected from food-handlers that
      annually refer to health center for getting a health certification and examined
      microscopically for G. lamblia cyst. Totally, 44 isolates were selected from 47
      Giardia positive samples. Cysts were partially purified by the sucrose density
      gradient method. After freeze-thaw cycles, genomic DNA was extracted using QIAamp
      Stool Mini kit. A single step PCR-RFLP method was used to amplify a 458bp
      fragment at the glutamate dehydrogenase (gdh) locus, restriction enzymes BspLI
      and RsaI were used for distinguish between genotypes A and B and their subgroups.
      RESULTS: Of 44 isolates, 24(54.5%) were sub-assemblage AII, 9(20.5%) group B
      including 7(15.9%) BIII and 2(4.6%) BIV sub-assemblage and 11(25%) isolates
      showed a mixed pattern of AII and B. Sub-assemblage AI was not detected in this
      study. CONCLUSION: The higher rate of sub-assemblage AII demonstrated an
      anthroponotic origin of the infection so infected food-handlers could directly
      transmit this protozoan to consumers via contaminated food and water. For finding
      of pattern of transmission and distribution of Giardia assemblages and sub
      assemblage, more studies in human and animal population in different regions are
      necessary.

PMID- 28761465
TI  - Absence of Asymptomatic Malaria Infection in a Cross-sectional Study in Iranshahr
      District, Iran under Elimination Programmes.
AB  - BACKGROUND: Asymptomatic malaria infection provides a reservoir of parasites,
      causing the persistence of malaria transmission. It accounts an important
      challenge for successful management of the control, elimination, and eradication
      programmes in any malaria-endemic region. This investigation was designed to
      assess the presence and the prevalence of asymptomatic carriers in Iranshahr
      district of Sistan and Baluchistan Province (2013-2014), with a considerable
      population movement, during the malaria elimination phase in Iran. METHODS:
      Finger-prick blood samples were collected from symptomless (n=250) and febrile
      (n=50) individuals residing in Iranshahr district, easthern Iran (Hoodian, Mand,
      Chah-e Giji, Jolgehashem, Esfand, Dalgan and Chahshour) during Jan 2013 to Dec
      2014, and Plasmodium infections were detected using light microscopic and highly
      sensitive nested-PCR techniques. RESULTS: Thick and thin Giemsa-stained blood
      smears were negative for Plasmodium parasites. In addition, based on nested-PCR
      analysis, no P. vivax, P. falciparum, and P. malariae parasites were detected
      among the studied individuals. CONCLUSION: Investigation the absence of
      asymptomatic carriers in Iranshahr district was illustrated and achieving malaria
      elimination in this area is feasible in a near future.

PMID- 28761466
TI  - Epidemiological Study of Toxocar canis in Children under 14-Years-Old and Dogs in
      Zabol and Chabahar Districts, Southeast of Iran.
AB  - BACKGROUND: The purpose of this study was seroepidemiological and parasitological
      assessment of Toxocara canis infection in children and dogs in Zabol and
      Chabahar, Iran. METHODS: This study was a descriptive-analytic study with a
      simple random sampling of children under 14 yr old, referring to urban, rural,
      and tribal laboratories of Zabol and Chabahar, Sistan and Baluchestan Province,
      Iran in 2016. Demographic data, clinical, and laboratory conditions of patients
      were collected through interviews, questionnaires, and blood count measuring. The
      prevalence of IgG antibodies against T. canis was assessed by ELISA. T. canis
      eggs in dogs (as the original host) were also assessed by examining animal feces.
      Then the data were analyzed using SPSS 19 software and descriptive statistics,
      chi-square and ANOVA statistical tests. RESULTS: Totally, 364 patients were
      enrolled, of which 51.6% were female and mean+/-SD age of participants was 7.2
      (+/-3.7) yr. IgG antibodies against T. canis was observed in 3.8% of cases. A
      significant association was found between the seroprevalence of T. canis and
      eosinophil (P=0.003) and red blood cell count (P=0.04). We also found a
      significant association between serological prevalence of T. canis and
      demographic parameters, such as city of residence (P=0.003), gender (P=0.04),
      consumption of vegetables (P=0.01), and the living place (P=0.04). Mean antibody
      titration was 2.2 +/-1.1, with statistically significant difference among age
      groups (P=0.001). In addition, T. canis infection was positive in 27.5% of dogs
      living in the study areas. CONCLUSION: High risk of infection represented in
      patients referring to laboratories of Zabol and Chabahar. In addition, given the
      fact that dogs are the final hosts to transfer Toxocara infection to humans, this
      study emphasizes the need to control the population of stray dogs in the region
      to prevent the development of disease in the human society.

PMID- 28761467
TI  - Prevalence of Intestinal Protozoa Infections and Associated Risk Factors among
      Schoolchildren in Sanandaj City, Iran.
AB  - BACKGROUND: Intestinal parasites are still a serious public health problem in the
      world, especially in developing countries. This study aimed to assess the
      prevalence of intestinal protozoa infections and associated risk factors among
      schoolchildren in Sanandaj City, Iran. METHODS: This cross-sectional study
      involving 400 schoolchildren was carried out in 2015. Each student was selected
      using systematic random sampling method. Questionnaire and observation were used
      to identify possible risk factors. Fresh stool samples were observed using formal
      ether concentration method. RESULTS: Five species of intestinal protozoa were
      identified with an overall prevalence of 42.3%. No cases of helminthes infection
      were detected. The predominant protozoa were Blastocys hominis (21.3%) and
      Entamoeba coli (4.5%). Overall, 143 (35.9%) had single infections and 26 (6.4%)
      were infected with more than one intestinal protozoa, in which 23 (5.9%) had
      double intestinal protozoa infections and 3 (0.5%) had triple infections. A
      significant relationship was observed between intestinal protozoa infection with
      economic status, water resources for drinking uses, and the methods of washing
      vegetables (P<0.05). CONCLUSION: Education programs on students and their
      families should be implemented for the prevention and control of protozoa
      infections in the study area.

PMID- 28761468
TI  - Seroepidemiological Study of Toxoplasma gondii Infection among Psychiatric
      Patients in Mashhad, Northeast of Iran.
AB  - BACKGROUND: Psychiatric patients have an increased risk of some infections like
      toxoplasmosis. Investigations on Toxoplasma gondii infection among psychiatric
      patients have been limited in Mashhad, Northeast of Iran. In this case-control
      study, prevalence of T. gondii was investigated by serological method. METHODS:
      This case-control study was performed among psychiatric patients admitted to
      Avicenna Hospital in Mashhad, Northeast of Iran. Three hundred and fifty
      inpatients and 350 controls were examined in 2012-2013 for detection of IgG and
      IgM antibodies against T. gondii in their blood sera by ELISA. Socio-demographic
      and clinical manifestations of the patients were obtained. RESULTS: Anti-T.
      gondii IgG antibodies was found in 164 (46.85%) of 350 psychiatric inpatients and
      120 (34.28%) of 350 controls. Seventeen (4.85%) of psychiatric individuals and 3
      (0.85%) of control group were IgM+/IgG- indicating acute form of toxoplasmosis.
      There were no statistically significant differences between the case and control
      groups. In patient group, schizophrenic patients had the highest positive rate
      (46.28%) and bipolar mood disorder had the second most prevalent rate (20%). Of
      162 schizophrenia patients, 65 (40.1%) had latent infection which was higher than
      that observed in controls. CONCLUSION: The prevalence of T. gondii infection
      among psychiatric patients suffering from schizophrenia was more in Mashhad,
      compared with control group.

PMID- 28761469
TI  - Parasitic Infections of Bicoloured White-toothed Shrew (Crocidura leucodon) from
      Dasht-e-Razan, Western Iran.
AB  - BACKGROUND: The prevalence and intensity of endo and ectoparasites in shrews
      inhabiting in the Dasht-e Razan of Hamedan Province, Iran, were determined in
      this study. METHODS: By live traps, 64 shrews belong to species bicoloured white
      toothed shrews (Crocidura leucodon) were trapped during 2010-2012. Captured
      animals were euthanized and their gender recorded. The blood thick and thin
      smears were stained with Geimsa and examined for protozoan parasites. Then,
      ectoparasites were collected and preserved in 70% ethanol and after necropsies;
      different organs were examined for helminthes. RESULTS: The prevalence of
      collected helminthes of Crocidura leucodon were; Capillaria crociduri (18.7%),
      Vigisolepis secunda (26.5%), Coronacantus sp (15.6%), Capillaria hokkaidensis
      (45.3%), and its ectoparasites were; Nymphs of three species of ticks;
      Haemaphysalis sp (32.8%), Ornitodoros sp (23.4%), Hyalomma sp (9.4%), one species
      of louse, Polyplax reclinata (18.7%) and one species of flea Leptopsylla sp
      (39.1%). Among the collected parasites, all helminthes and one sucking louse, P.
      reclinata are reported for the first time in Iran. Statistically analysis with
      the Chi-square test did not show any significant relation between gender and
      endoparasites (P>0.05), but the ectoparasites had significant differences with
      gender (P<0.05). No significant correlation was found between the altitude and
      the parasite species richness (Spearman's test: P>0.05). CONCLUSION: This study
      reports 9 species of parasites and 5 species of them were identified for the
      first time in Iran and some of them are vectors of several important zoonoses
      agents.

PMID- 28761470
TI  - Intraperitoneal Inoculation: An Atypical Route of Trichinella spiralis Infection.
AB  - BACKGROUND: The intraperitoneal injection is a common method for establishing the
      experimental animal model infected with parasites. The aim of this study was to
      investigate if the intraperitoneal injection was another route of Trichinella
      spiralis infection. METHODS: From June to July 2015, twenty BALB/c mice were
      intraperitoneally injected with 300 T. spiralis muscle larvae in Department of
      Parasitology, Medical College, Zhengzhou University, China. The larvae per gr
      (LPG) muscle from the infected mice and the reproductive capacity index (RCI) of
      T. spiralis were calculated. RESULTS: Sixty percent (12/20) mice injected were
      successfully infected at 35 day post injection (dpi), but the muscle larval
      burden (381.53 larvae per gr) and reproductive capacity index (32.33) in infected
      mice was lower. CONCLUSION: A mechanical force indicated as a possible mechanism
      in successful larval invasion of almost all kind of host tissues. However, the
      exact migratory route of larvae from peritoneal cavity into small intestine is
      not clear.

PMID- 28761471
TI  - Detection of Toxocara spp. Eggs in the Soil of Public Places in and Around of
      Ardabil City, Northwestern Iran.
AB  - BACKGROUND: Human toxocariasis is contained in the list of neglected diseases.
      The infection occurs after ingestion of embryonated eggs in contaminated soil.
      The present study was carried out to estimate the extent of soil contamination
      with Toxocara spp. eggs in the public places. METHODS: Soil samples were
      collected randomly from 41 public places in various parts in and around of
      Ardabil, Iran, between March 2013 and March 2014. Data were examined by
      microscopy following sodium nitrate flotation. RESULTS: Of the 200 collected soil
      samples, 35 (17.5%) were positive for soil parasites. The eggs of Toxocara spp.
      were found in 14 (7%) soil samples. CONCLUSION: This investigation gives baseline
      knowledge regarding soil contamination with Toxocara spp. eggs in Ardabil city
      and provides information for local control of toxocariasis.

PMID- 28761473
TI  - Multiple Complications by Hydatid Cyst-induced Budd Chiary Syndrome: A Case
      Report.
AB  - A case of the Budd Chiary Syndrome (BCS) in a 43-yr-old man with hydatid cyst
      (HC) in the liver is reported from Imam Ali Hospital, Kermanshah, western Iran in
      2016. This case was complicated by inferior vena cava (IVC) thrombosis, right
      atrial clot and pulmonary emboli. Compression of IVC was the likely mechanism.
      Abdominal ultrasonography revealed a huge HC located in segments near IVC and
      caused compression of IVC. Transthoracic echocardiography (TTE) revealed IVC and
      right atrium thrombosis, however pulmonary emboli was not documented in TTE but
      intra operative exploration showed multiple clot in main and left pulmonary
      artery branch. The patient recovered after open-heart surgery with removal of
      right atrial, IVC and pulmonary artery emboli. BCS should be looked for routinely
      in patients with HC of the liver.

PMID- 28761472
TI  - Pathogenic Acanthamoeba T4 Genotype Isolated from Mucosal Tissue of a Patient
      with HIV Infection: A Case Report.
AB  - Opportunistic infections due to free-living amoebae such as Granulomatous Amoebic
      Encephalitis (GAE), cutaneous acanthamoebiasis and disseminated infections could
      be the causative agent of mortality in people living with HIV/AIDS. In this
      study, we report the occurrence of the Acanthamoeba belonging to the T4 genotype
      isolated from nasal and oral swabs of a 15-yr-old man with HIV infection. HIV was
      confirmed using ELISA kit and RT-PCR assay. The isolated strain showed pathogenic
      potential using thermo and osmotolerance assays. This patient might be vulnerable
      to develop GAE or disseminated infections and depending on the immunologic status
      of the patient, this could be a health threat. Monitoring of such patients,
      appropriate diagnostic procedures and improved-HIV related care can alter the
      outcome of such infections.

PMID- 28761474
TI  - Cystic Echinococcosis: A Rare Case of Brain Localization.
AB  - Although Hydatid disease eradicated in many countries, it is still widespread in
      communities where agriculture is dominant. Cystic hydatidosis is significant
      public health problem in the regions with endemic echinococcosis. The hydatid
      cysts tend to form mostly in the liver or lung. Brain involvement is very rare.
      In the present report, we describe magnetic resonance imaging findings in an 18
      yr-old male with cerebral echinococcosis, in Shahid Madani Hospital, Karaj, Iran
      in 2015. The patient, presented with headache, hemiparesis, impairment of speech,
      vomiting, and nausea. Computed tomography, magnetic resonance imaging, and
      surgical exploration proved a cyst in the superior portion of left temporal lobe.
      Pathological examination showed it to be a solitary primary cerebral hydatid
      cyst.

PMID- 28761475
TI  - The Helminths Causing Surgical or Endoscopic Abdominal Intervention: A Review
      Article.
AB  - BACKGROUND: Helminths sometimes require surgical or endoscopic intervention.
      Helminths may cause acute abdomen, mechanical intestinal obstruction,
      gastrointestinal hemorrhage, perforation, hepatitis, pancreatitis, and
      appendicitis. This study aimed to determine the surgical diseases that helminths
      cause and to gather, analyze the case reports, case series and original articles
      about this topic in literature. METHODS: This study was designed as a
      retrospective observational study. In order to determine the studies published in
      literature, the search limits in Pub-Med database were set to 1 Jan 1957 and 31
      Mar 2016 (59 yr), and the articles regarding Helminth-Surgery-Endoscopy were
      taken into examination. Among 521 articles scanned, 337 specific ones were
      involved in this study. RESULTS: The most common surgical pathology was found to
      be in Ascaris lumbricoides group. Enterobius vermicularis was found to be the
      parasite that caused highest amount of acute appendicitis. Anisakiasis was
      observed to seem mainly because of abdominal pain and mechanical intestinal
      obstruction. Strongyloides stercoraries causes duodenal pathologies such as
      duodenal obstruction and duodenitis. Taenia saginata comes into prominence with
      appendicitis and gastrointestinal perforations. Fasciola hepatica exhibits
      biliary tract involvement and causes common bile duct obstruction. Hookworms were
      observed to arise along with gastrointestinal hemorrhage and anemia. Trichuris
      trichiuria draws attention with gastrointestinal hemorrhage, mechanical
      intestinal obstruction. CONCLUSION: Helminths may lead to life-threatening clinic
      conditions such as acute abdomen, gastrointestinal perforation, intestinal
      obstruction, and hemorrhages. There is a relationship between surgery and
      helminths. It is very important for surgeons to consider and remember helminths
      in differential diagnoses during their daily routines.

PMID- 28761477
TI  - Molecular and Morphological Characterizations of Echinococcus granulosus from
      Human and Animal Isolates in Kashan, Markazi Province, Iran.
AB  - BACKGROUND: One of the most important zoonotic helminths in the world is known as
      Echinococcus granulosus. Different strains of the E. granulosus have been
      described based on morphological and molecular characterizations, however, there
      is limited information regarding the characteristics of the phenotypes and
      genotypes of E. granulosus in Iran. METHODS: The present study was prepared to
      evaluate the phenotypic and genotypic diversity of E. granulosus isolates
      collected from human, goat, sheep, and cattle based on 19 standard morphometric
      parameters and mitochondrial and nuclear genes (CO1, ND1, and ITS1) in Kashan,
      Markazi Province, Iran during 2013-2014. RESULTS: The biometric analysis for the
      19 characters revealed that the 19 morphometric values of cattle isolates were
      exceptionally higher than human, goat, and sheep isolates (P<0.05). Molecular
      analysis confirms the morphological findings. Phylogenic analysis of the CO1,
      NAD1 and ITS1 genes for all isolates, independent of the host, revealed that the
      common sheep strain (G1) is traveling among livestock in Kashan and the strains
      are highly adapted to goats, cattle, sheep, and humans. CONCLUSION: Both
      morphological and molecular results of this study indicated that the only
      genotype G1 of E. granulosus travels between humans and other intermediate hosts
      of this parasite in the area study.

PMID- 28761476
TI  - Prevalence, Clinical Manifestations and Genotyping of Cryptosporidium Spp. in
      Patients with Gastrointestinal Illnesses in Western Iran.
AB  - BACKGROUND: Cryptosporidium species are recognized as important gastrointestinal
      pathogens. This study was conducted to identify the prevalence, clinical
      manifestations and genotyping of Cryptosporidium spp. in patients with
      gastrointestinal illnesses (GIs) in western Iran. METHODS: Overall, 1301 fecal
      samples were collected from patients with GIs referred to the 12 clinical
      laboratories in Nahavand County, west of Iran. Modified Ziehl-Neelsen staining
      method was used to identify the oocysts. DNA was extracted from positive samples
      and Cryptosporidium spp. were characterized by Nested PCR and sequence analysis
      of the 60-kDa glycoprotein (gp60) gene. Data analysis was performed using SPSS
      ver. 16. RESULTS: Prevalence of cryptosporidiosis was 1.3% (17/1301).
      Cryptosporidium infection was significantly associated with vomiting and nausea
      (P=0.001, OR=0.013; CI 95%=0.004- 0.044), abdominal pain (P=0.018, OR=0.073; CI
      95%=0.008- 0.633) and diarrhea (P=0.001, OR=0.092; CI 95%=0.023- 0.362). Of the
      17 isolates typed, 11 belonged to the C. parvum IId subtype family (subtypes
      IIdA26G1 and IIdA20G1) and six belonged to the C. parvum IIa subtype family
      (subtypes IIaA15G2R1 and IIaA16G3R1). There was no significant difference between
      sub-type families IIa and IId in occurrence of clinical symptoms (P= 0.75).
      CONCLUSION: Improved hygiene and avoidance of contact with animals and
      contaminated soil should be advocated to reduce the occurrence of Cryptosporidium
      infections, especially in children.

PMID- 28761478
TI  - M-RNA Gene Expression of INF-Gamma and IL-10 during Intestinal Phase of
      Trichinella spiralis after Myrrh and Albendazole Treatment.
AB  - BACKGROUND: The protective response developed against Trichinella spiralis
      infection provokes immune and inflammatory responses mediated by cytokines
      released from T helper cells. We aimed to evaluate the effect of albendazole or
      myrrh on the expression of IFN-gamma and IL-10 in BALB/c mice infected with T.
      spiralis. METHODS: This study was done at the Animal House of Faculty of
      Medicine, Assiut University (Assiut, Egypt) from April to December 2015. Mice
      were infected with 300 T. spiralis larvae and treated with albendazole (50 mg/kg
      per day) or myrrh (500 mg/kg per day) for 3 consecutive days post-infection (pi).
      The expression of INF-gamma and IL-10 was detected in the intestinal tissue by
      reverse transcription (RT) PCR. RESULTS: The expression of IFN-gamma in mice
      treated with albendazole and myrrh was detected on days 3 and 15 pi respectively.
      In the control group, it was found on days 5, 10, 15 and 20 pi with the highest
      expression on day 15 pi. The expression of IL-10 was detected on days 3, 20 pi in
      the albendazole and myrrh treated groups, respectively. In the control group, IL
      10 expression appeared on days 5 and day 20 pi. CONCLUSION: The target of
      albendazole and myrrh on the profile of IFN-gamma and IL-10 on these cytokines
      were encouraging to reinforce their therapeutic use against trichinellosis.

PMID- 28761479
TI  - Surveillance and Molecular Identification of Acanthamoeba and Naegleria Species
      in Two Swimming Pools in Alexandria University, Egypt.
AB  - BACKGROUND: Swimming in contaminated water was reported to be associated with
      Acanthamoeba and N. fowleri human infections. The present study was carried out
      with the aim of isolation and identification of the different species of
      Acanthamoeba and Naegleria from two swimming pools in Alexandria University.
      METHODS: Samples were collected from the swimming pools of Alexandria University
      Stadium and Faculty of Agriculture-Alexandria University during the period from
      May 2012 to April 2013. RESULTS: Free-living amoebae were prevalent in the
      collected samples. Molecular characterization confirmed the identity of ten
      Acanthamoeba isolates and seven Naegleria isolates. Acanthamoeba T3, T4, T5, T11
      and T15 genotypes were identified. Acanthamoeba T4 was the most prevalent
      genotype. CONCLUSION: The relatively high prevalence of Acanthamoeba, especially
      genotype T4, indicates the presence of a health hazard to swimmers particularly
      those wearing contact lenses. Naegleria fowleri was not found during the present
      study.

PMID- 28761480
TI  - Detection of Potentially Diagnostic Leishmania Antigens with Western Blot
      Analysis of Sera from Patients with Cutaneous and Visceral Leishmaniases.
AB  - BACKGROUND: Visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) are
      important public health problems in Iran. We aimed to evaluate the diagnostic
      potential of Western blot (WB) compared with indirect immunofluorescence test
      (IFAT) to serodiagnosis of leishmaniasis. METHODS: This study was performed from
      2010-2014 and participants were different parts of Iran. Serum samples were
      obtained from 43 patients with proven CL, 33 patients with proven VL, 39 patients
      with other parasitic diseases and 23 healthy individuals. RESULTS: WB sensitivity
      for CL and VL was 100% and 91%, compared to IFA 4.6% and 87.8%, respectively.
      Sera from patients with CL and VL recognized numerous antigens with molecular
      weights ranging from 14 to 68 kDa and 12 to 94 kDa, respectively. The most
      sensitive antigens were 14 and 16 kDa for CL recognized by 100% of the sera from
      patients with proven CL and 12, 14 and 16 kDa for VL, recognized by 63.6%, 100%
      and 63.6% of the sera from patients with proven VL respectively. WB analysis is
      more sensitive than IFAT for the diagnosis of leishmaniasis particularly in cases
      of cutaneous leishmaniasis. The 12, 14 and 16 kDa can be valuable diagnostic
      molecules for serodiagnosis of leishmaniasis because at least two immunogenic
      molecules were simultaneously detected by all patient sera, as well as produced
      antibodies against these antigens have no cross-reactivity with other control
      groups. CONCLUSION: WB could be useful for screening and serodiagnosis of CL and
      VL in epidemiologic studies in endemic areas.

PMID- 28761481
TI  - Comparison of Three PCR-based Methods for Simplicity and Cost Effectiveness
      Identification of Cutaneous Leishmaniasis Due to Leishmania tropica.
AB  - BACKGROUND: To compare three molecular methods, PCR-RFLP for internal transcribed
      spacer, PCR sequencing and high resolution melting analysis shown reliable
      sensitivity and specificity for detecting Leishmania tropica as a model for
      cutaneous leishmaniasis (CL) as the perspective overview for scientific and
      economic approaches. METHODS: This study was carried out between 2015 and 2016 in
      Leishmaniasis Research Center in Kerman University of Medical Sciences, Kerman,
      Iran. The positives smears (n=50) were obtained from patients referred from the
      health clinics in a major anthroponotic CL (ACL) focus, southeastern Iran. Only
      smear preparations with the same grade were selected according to the method
      described by the WHO for future PCR assays. RESULTS: All three molecular methods
      had capability to identify positive samples at species level with the same
      specificity and sensitivity. However, these techniques were different in
      simplicity, consuming time, and cost effectiveness. Although additional enzymatic
      process in PCR-RFLP provided good resolution to find Leishmania species but this
      would cause time and cost increases. CONCLUSION: HRM (high resolution melting) is
      a relatively new technique that allows direct characterization of PCR amplicons
      in a closed system with more simplicity, cost effectiveness and time-consuming
      compared with other PCR-based assays for epidemiological or clinical
      identification purposes.

PMID- 28761482
TI  - Molecular Characterization and Analysis of 16S Ribosomal DNA in Some Isolates of
      Demodex folicullorum.
AB  - BACKGROUND: Demodicosis is one of the most prevalent skin diseases resulting from
      infestation by Demodex mites. This parasite usually inhabits in follicular
      infundibulum or sebaceous duct and transmits through close contact with an
      infested host. METHODS: This study was carried from September 2014 to January
      2016 at Tehran University of Medical Sciences, Tehran, Iran. DNA extraction and
      amplification of 16S ribosomal RNA was performed on four isolates, already
      obtained from four different patients and identified morphologically though
      clearing with 10% Potassium hydroxide (KOH) and microscopical examination.
      Amplified fragments from the isolates were compared with GeneBank database and
      phylogenetic analysis was carried out using MEGA6 software. RESULTS: A 390 bp
      fragment of 16S rDNA was obtained in all isolates and analysis of generated
      sequences showed high similarity with those submitted to GenBank, previously.
      Intra-species similarity and distance also showed 99.983% and 0.017,
      respectively, for the studied isolates. Multiple alignments of the isolates
      showed Single Nucleotide Polymorphisms (SNPs) in 16S rRNA fragment. Phylogenetic
      analysis revealed that all 4 isolates clustered with other D. folliculorum,
      recovered from GenBank database. Our accession numbers KF875587 and KF875589
      showed more similarity together in comparison with two other studied isolates.
      CONCLUSION: Mitochondrial 16S rDNA is one of the most suitable molecular barcodes
      for identification D. folliculorum and this fragment can use for intra-species
      characterization of the most human-infected mites.

PMID- 28761483
TI  - Road Killed Carnivores Illustrate the Status of Zoonotic Helminthes in Caspian
      Sea Littoral of Iran.
AB  - BACKGROUND: Carnivore carcasses on the roads can be regarded as study materials
      in parasitology and eco-epidemiology. Stray carnivores such as dogs and cats are
      known to harbor so many different pathogens like zoonotic helminthes. The current
      investigation, apparent the status of the helminthic parasites found in road
      killed carnivores from different parts of Guilan Province north of Iran. METHODS:
      Fifty road killed carnivores including 27 stray dogs (Canis familiaris), 11
      golden jackals (Canis aureus) and 12 stray cats (Felis catus) were collected from
      21 locations of Guilan Province, during Apr to Nov 2015. Internal organs of the
      carcasses, including digestive tract, heart, kidneys, lungs, liver, skin, eyes as
      well as muscles were carefully inspected and sampled for helminthological
      investigation. RESULTS: About 80% of the 50 carnivores, (stray dogs 77.77%,
      golden jackals 81.81%, and stray cats 91.66%) were found naturally infected with
      helminthic parasites. Dipylidum caninum, Toxocara cati, Toxocara canis,
      Toxascaris leonine, Ancylostoma caninum, Ancylostoma tubaeforme, Dirofilaria
      immitis, Dioctophyma renale, Dipylidum caninum, Echinococcus granulosus,
      Mesocestoides spp., Taenia hydatigena, Taenia hydatigera, Joyuxiella spp.,
      Spirometra spp. are reported herein. CONCLUSION: The prevalent occurrence of
      zoonotic helminthes such as T. canis, T. cati, T. leonina, E. granulosus, D.
      immitis and D. renale in stray carnivores should be considered as a public health
      hazard, specifically within a vast tourism area like Guilan Province.

PMID- 28761484
TI  - Comparison of Three Different DNA Extraction Methods for Linguatula serrata as a
      Food Born Pathogen.
AB  - BACKGROUND: One of the most important items in molecular characterization of food
      borne pathogens is high quality genomic DNA. In this study, we investigated three
      protocols and compared their simplicity, duration and costs for extracting
      genomic DNA from Linguatula serrata. METHODS: The larvae were collected from the
      sheep's visceral organs from the Yazd Slaughterhouse during May 2013. DNA
      extraction was done in three different methods, including commercial DNA
      extraction kit, Phenol Chloroform Isoamylalcohol (PCI), and salting out.
      Extracted DNA in each method was assessed for quantity and quality using
      spectrophotometery and agarose gel electrophoresis, respectively. RESULTS: The
      less duration was regarding to commercial DNA extraction kit and then salting out
      protocol. The cost benefit one was salting out and then PCI method. The best
      quantity was regarding to PCI with 72.20+/-29.20 ng/MUl, and purity of
      OD260/OD280 in 1.76+/-0.947. Agarose gel electrophoresis for assessing the
      quality found all the same. CONCLUSION: Salting out is introduced as the best
      method for DNA extraction from L. seratta as a food-borne pathogen with the least
      costand appropriate purity. Although, the best purity was regarding to PCI but
      PCI is not safe as salting out. In addition, the duration of salting out was less
      than PCI. The least duration was seen in commercial DNA extraction kit, but it is
      expensive and therefore is not recommended for developing countries where
      consumption of offal is common.

PMID- 28761485
TI  - Molecular Determination of Fasciola Spp. Isolates from Domestic Ruminants Fecal
      Samples in the Northwest of Iran.
AB  - BACKGROUND: Fasciola species are the main causes for fascioliasis with great
      financial losses and are among the most important food/water-borne parasites
      worldwide. The basic proceedings such as epidemiology and effective control of
      fascioliasis rely mainly on precise identification of Fasciola species. The
      present study was conducted to determine the Fasciola species in ruminant fecal
      samples from East Azerbaijan Province in Iran. METHODS: Overall, 2012 fecal
      samples were collected and processed initially for microscopic examination of
      Fasciola eggs in 2014-15. Then, recovered eggs were subjected to molecular
      identification. A fragment of 618 bp of the 28S rRNA gene pertaining to Fasciola
      genus was amplified under PCR. The amplified fragment was restricted by fast
      digest Ava II enzyme in order to a Restriction Fragment Length Polymorphism.
      RESULTS: Based on microscopic examination, 72 samples were infected, from which,
      10 and 62 cases pertained to cattle and sheep samples respectively. Based on
      RFLP, the PCR products restricted by the Ava II restriction enzyme produced 529
      bp fragments only. According to the positive controls, all restriction patterns
      were related to Fasciola hepatica, while no restriction patterns were linked to
      F. gigantica. CONCLUSION: Based on PCR-RFLP, F. hepatica was dominant species in
      animals of the studied areas and no evidence of F. gigantica was observed.
      Therefore, further field studies to verify these results are suggested.

PMID- 28761486
TI  - Considerable Genetic Diversity of Trichomonas vaginalis Clinical Isolates in a
      Targeted Population in South of Iran.
AB  - BACKGROUND: The present study aimed to characterize genetically and to compare
      the most frequently occurring strains of Trichomonas vaginalis isolated from
      southern Iran. METHODS: Totally, 150 vaginal swab and urine specimens were
      collected from symptomatic and asymptomatic women from May 2012 to Jun 2013. This
      study implemented a sensitive and reliable PCR-restriction fragment length
      polymorphism (RFLP) typing method on the actin gene. Moreover, one representative
      sample of each identified genotype was subjected to sequencing. RESULTS: Twenty
      four T. vaginalis isolates were positive and 6 distinct electrophoretic patterns
      (H, E, G, I, M, N) were identified. Genotypes H and I were found to be more
      prevalent (50 and 37.5%) in Kerman and Shiraz, respectively. The phylogenetic
      analysis showed that two isolates were located as a separated clade with the
      other T. vaginalis isolates. CONCLUSION: The obtained findings showed a
      considerable genetic polymorphism of clinical isolates from the population
      studied. More studies may be warranted in future as to unveiling any possible
      links between a given genotype/cluster and pathogenic behavior of T. vaginalis.

PMID- 28761487
TI  - Parasitological, Serological and Molecular Study of Dirofilaria immitis in
      Domestic Dogs, Southeastern Iran.
AB  - BACKGROUND: Dirofilariasis is a serious and potentially deadly condition in dogs
      and one of the zoonotic filarial infections, which inadvertently affects the
      humans. The objectives of this study were to determine the seroprevalence and the
      molecular identity of dirofilariasis in Kerman Province, southeastern Iran
      between Jul and Aug 2013. METHODS: A hundred and forty-nine domestic dogs were
      randomly selected and five ml blood samples were taken from each dog. One ml of
      anticoagulant (EDTA) was used for each test in the parasitological study
      (modified Knott's test) and sera samples were examined, using ELISA kit to detect
      Dirofilaria immitis antigen. Extracted DNA of all positive blood samples was used
      for molecular characterization and sequencing. RESULTS: Four (2.7%) domestic dogs
      of the total 149 domestic dogs were infected with micofilariae of D. immitis,
      while the serological study showed 8 (5.4%) domestic dogs were infected with D.
      immitis. No significant difference, however, was found between dirofilariasis
      infection and gender. On the other hand, a significant difference was observed
      between dirofilariasis infection and age (P<0.05). Based on the PCR findings,
      among the total specimens, 6 positive samples were characterized as D. immitis.
      CONCLUSION: Dirofilariasis occurred when there was low endemicity in the dogs.
      Such dogs could be a potential source of infection for humans. These findings
      could help in better understanding of the epidemiological aspects of D. immitis
      in the southeastern parts of Iran.

PMID- 28761488
TI  - Intestinal Helminths in Different Species of Rodents in North Khorasan Province,
      Northeast of Iran.
AB  - BACKGROUND: Rodents are an important source of zoonotic diseases for human. The
      aim of this study was to determine the infectivity of rodents with intestinal
      helminths in North Khorasan Province, Iran. METHODS: One hundred and thirteen
      rodents were collected using different collection methods such as kill and live
      traps, digging of their burrow, filling of their hiding places with water and
      hand net during 2011-2013. Their alimentary canals were removed in the laboratory
      and helminths were determined in the department of parasitology, Tehran
      University of Medical Sciences. RESULTS: Thirteen species of helminths parasites
      were found in 13 species of rodents, including Aspiculuris tetraptera,
      Hymenolepis diminuta, Nippostrongylus brasiliensis, Protospirura Seurat,
      Rictolaria ratti, Skrjabinitaenia lobata, Streptopharagus kuntzi, Syphacia
      obvelata, Taenia taeniaeformis, Trichuris muris, Cysticercus fasciolaris,
      Acanthocephal. spp and Trichuris spp. Some of them were reported for the first
      time in new host in Iran. S. obvelata and A. tetraptera were the most frequent
      parasites and P. Seurat, R. ratti and C. fasciolaris were found only in one
      rodent. CONCLUSION: This is the first study to investigate the intestinal
      parasites in rodents in this area. Among different species identified, some of
      helminths were reported in new host.

PMID- 28761489
TI  - The Impact of Different Copro-preservation Conditions on Molecular Detection of
      Cryptosporidium Species.
AB  - BACKGROUND: We aimed to evaluate different copro-preservation conditions along
      the duration of one month for a better outcome of molecular diagnosis of
      Cryptosporidium species. METHODS: Ten samples out of 380 fresh stool samples
      collected from patients with diarrhea proved positive after direct examination,
      concentration, staining and confirmed by immunochromatographic test. The study
      was conducted at the Diagnostic and Research Unit of Parasitic diseases, Faculty
      of Medicine, Ain Shams University at the time interval from July 2014 to December
      2015. Each stool sample was preserved in five different conditions; freezing at 
      20  degrees C, 70% ethyl alcohol, 10% formalin, 2.5% potassium dichromate (K
      dichromate) at 4  degrees C and 2.5% K dichromate at room temperature (RT). Then
      DNA extraction and nested PCR, with Cryptosporidium oocyst wall protein (COWP)
      gene were done from each sample at zero time (fresh specimens) as a standard for
      comparison with the preservation conditions at 10, 20 and 30 d. RESULTS:
      Sensitivity of studied preservative conditions along the whole study duration
      showed best outcome from freezing at -20  degrees C (80%) then K dichromate (4 
      degrees C) (73.3%) followed by K dichromate (RT) (66.7%), then alcohol (33.3%),
      while formalin was the worst (0%) with a highly significant comparative outcome
      between the different conditions. Along the three extraction intervals, K
      dichromate (RT), unlike all the rest of conditions lacks the consistent
      preservative action. CONCLUSION: Our study highlights freezing at -20  degrees C
      to be the most suitable condition for preservation followed by K dichromate at 4 
      degrees C, K dichromate at RT, then 70% ethyl alcohol. Formalin (10%) is better
      to be avoided.

PMID- 28761490
TI  - Epidemiology of Urinary Schistosomiasis among School Children in the Alsaial
      Alsagair Village, River Nile State, Sudan.
AB  - BACKGROUND: Schistosomiasis is a debilitating disease, infects millions of people
      in tropical and subtropical regions. This study assessed the situation of the
      urinary schistosomiasis among schoolchildren of the Alsaial Alsagair village,
      Sudan. METHODS: A cross-sectional survey was carried out in 2016, in the Alsaial
      Alsagair village, and 385 samples of urine were collected and processed using the
      centrifugation/sedimentation technique. RESULTS: The overall prevalence and
      intensity of the disease among the pupils studied were 1.82% and 40.1 eggs/10ml
      urine, respectively. The prevalence of infection among male pupils was 3.1%, and
      for females was 0.52%, while the intensity among males was 42.3 eggs/10ml and for
      females was 27 eggs/10ml urine. No significant difference in the disease
      prevalence between the 7-10 yr age group and the 11-14 yr age group was found,
      while the over 14 yr age group was found to be free from infection. However, a
      considerably higher intensity of the parasite was found among the 7-10 yr age
      group compared to the other age group infected. A high prevalence and intensity
      of infection was observed among pupils who were active in swimming and working in
      the fields. Most of the pupils interviewed were found to be unaware of the
      disease and the prevalence and intensity of the infection was found to be higher
      among the group who were aware of the disease. CONCLUSION: Findings show the need
      for an integrated control program against urinary schistosomiasis including the
      treatment of all infected children and the implementation of a health education
      program.

PMID- 28761491
TI  - Evaluation of Microsatellites Markers to Discriminate Four Main Taeniid Tapeworms
      of Dogs.
AB  - BACKGROUND: Echinococcus granulosus, Taenia multiceps, Taenia ovis and Taenia
      hydatigena are among the most prevalent taeniid species of dogs. These tapeworms
      infect ruminant and humans as intermediate hosts and domestic/wild carnivores as
      the definitive hosts. Molecular tools using hypervariable microsatellite regions
      might provide more information about parasite variation. Highly variable and
      specific tools are needed for transmission tracking studies of canine
      echinococcosis as an essential element for implementation of hydatid control
      programs. Suitable microsatellite markers used so far are EmsJ, EmsK, EmsB,
      EMms1, Egmsca1, Egmsga1, U1 snRNA. The purpose of the present study was to
      determine the microsatellite variability of EmsB as well as six other
      microsatellites in major taeniid species infecting dogs in Iran. METHODS: Twenty
      isolates of each of the four Taeniidae tapeworms were collected from sheep during
      routine veterinary inspection in Tehran, Alborz and Kerman provinces from October
      2010 to May 2011. After DNA extraction, PCR was set up with optimum conditions
      using specific primers for each individual microsatellite marker. All the PCR
      products were evaluated by agarose gel electrophoresis. We used SDS-PAGE for
      evaluating patterns of PCR products in the tapeworms. RESULTS: E. granulosus as
      well as Taenia species could be differentiated based on EmsB microsatellite
      patterns. The electrophoresis patterns of two taeniid genera were readily
      distinguishable. EmsB could be specifically used in epidemiological studies of
      canine echinococcosis. CONCLUSION: Different patterns of EmsB proved this
      microsatellite marker as a reliable tool for epidemiological studies on canine
      echinococcosis.

PMID- 28761492
TI  - Gastrointestinal Helminths and Ectoparasites in the Stray Cats (Felidae: Felis
      catus) of Ahar Municipality, Northwestern Iran.
AB  - BACKGROUND: The stray cats are considered as the sources of emerging humans and
      domestic livestock pathogens and the zoonoses of public health importance. The
      present study was aimed to elucidate intestinal helminth infections and
      infestation with ectoparasites of the stray cats of Ahar City, northwestern Iran.
      METHODS: Totally, 51 stray cats were randomly trapped from different parts of the
      city between Mar and Nov 2013. The cats were assessed for ectoparasites by hair
      brushing, skin scraping, acetate tape preparation and othic swabs. They were
      euthanized and inspected for helminths infection. RESULTS: Overall prevalence of
      helminths and flea were 44/51 (86.3%) and 31/51 (60.78%), respectively. The
      infection rates were significantly different among different age groups (P<0.05).
      Of the 282 isolated helminths, three species of nematodes (Toxocara cati (86.3%),
      T. leonina (11.77%), Ancylostoma tubaeforme (5.9%)) and four species of cestodes
      (Taenia taeniaeformis (64.7%), Mesocestoides lineatus (49.02%), Dipylidium
      caninum (29.41%), T. hydatigena (19.6%)) were identified. The predominant
      infectious helminths in all the infected cats were T. cati (86.3% with egg per
      gram of feces 27.75+/-9). Of the 270 collected fleas, two species of
      Ctenocephalides felis (80%) and C. canis (20%) were notably frequent in the cats
      aged 2-3-year-old. The average number of fleas per each infected cat was recorded
      as 5.29, with no incidence of cross-infection. CONCLUSION: The results indicated
      the high rate of helminths infections and flea infestation in the urban stray
      cats of which Toxocara cati and Ctenocephalides felis may play important roles as
      zoonotic agents in the region.

PMID- 28761493
TI  - Gluteal Hydatid Cyst: Report of a Case from Iran.
AB  - Hydatid cyst involves both hard and soft tissues even without the evidence of the
      disease in liver or lungs; however, this manifestation is very rare, particularly
      in musculoskeletal regions). The current report describes a case with primary
      diagnose of cystic gluteal swelling leading to diagnose of hydatid cyst after
      surgical exploration in an 80-yr-old woman the Surgical Outpatient Department,
      Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran,
      Iran. During surgery, the cavity was washed by silver nitrate and the cyst
      content was appropriately evacuated. The patient had completed a short course of
      albendazole postoperatively. Early postoperative complications were not appeared.
      The patient was followed for 6 months with no evidence of recurrence or
      complications.

PMID- 28761494
TI  - Underdiagnosed Complicated Plasmodium vivax Malaria in a Child: Need to Think.
AB  - Malaria is major cause of morbidity and mortality worldwide. The highest
      incidence of malaria in the world is South East Asia. India is most affected
      country followed by Indonesia and Myanmar. The prevalence of malaria varies
      according to geographical region. Diagnosis of malaria infection has been
      underestimated. Here, we report a case of under-diagnosed complicated vivax
      malaria in one-yr-old child in 2016. Early diagnosis and prompt treatment can
      reduce both morbidity and mortality in complicated malaria infection.

PMID- 28761496
TI  - Antioxidant Properties of Crude Extract, Partition Extract, and Fermented Medium
      of Dendrobium sabin Flower.
AB  - Antioxidant properties of crude extract, partition extract, and fermented medium
      from Dendrobium sabin (DS) flower were investigated. The oven-dried DS flower was
      extracted using 100% methanol (w/v), 100% ethanol (w/v), and 100% water (w/v).
      The 100% methanolic crude extract showed the highest total phenolic content
      (40.33 +/- mg GAE/g extract) and the best antioxidant properties as shown by
      DPPH, ABTS, and FRAP assays. A correlation relationship between antioxidant
      activity and total phenolic content showed that phenolic compounds were the
      dominant antioxidant components in this flower extract. The microbial
      fermentation on DS flower medium showed a potential in increasing the phenolic
      content and DPPH scavenging activity. The TPC of final fermented medium showed
      approximately 18% increment, while the DPPH of fermented medium increased
      significantly to approximately 80% at the end of the fermentation. Dendrobium
      sabin (DS) flower showed very good potential properties of antioxidant in crude
      extract and partition extract as well as better antioxidant activity in the
      flower fermented medium.

PMID- 28761495
TI  - Development and Validation of a HPLC-UV Method for the Evaluation of Ellagic Acid
      in Liquid Extracts of Eugenia uniflora L. (Myrtaceae) Leaves and Its Ultrasound
      Assisted Extraction Optimization.
AB  - A simple HPLC-UV method has been developed and validated for the quantification
      of ellagic acid (EA) in ethanol extracts of Eugenia uniflora L. (Myrtaceae)
      leaves. The ultrasound-assisted extraction (UAE) optimization was performed using
      a Box Behnken design (33) combined with response surface methodology to study the
      effects of the ethanol concentration (%, w/w), extraction time (minutes), and
      temperature ( degrees C) on the EA concentration. The optimized results showed
      that the highest extraction yield of EA by UAE was 26.0 MUg mL-1 when using 44%
      (w/w) ethanol as the solvent, 22 minutes as the extraction time, and 59 degrees C
      as the extraction temperature. The concentration of EA in relation to the
      predicted value was 93.7%  +/-  0.4. UAE showed a strong potential for EA
      extraction.

PMID- 28761497
TI  - The Effects of Aromatherapy Massage on Sleep Quality of Nurses on Monthly
      Rotating Night Shifts.
AB  - The goal of this study is to examine the effects of aromatherapy massage on sleep
      quality of nurses with monthly rotating night shifts. Subjects were enrolled at a
      medical center in central Taiwan with overall score >= 5 of Pittsburgh Sleep
      Quality Index (PSQI) and randomly assigned to the treatment or control groups.
      They were validated by pretests during their first graveyard shift in the trial
      period and the sleep quality information was collected by using the PSQI and
      sleep detectors. During the second graveyard shift, the treatment group received
      aromatherapy massage and the control group rested in the same aromatherapy room
      after work. All subjects filled out the PSQI surveys and the sleep quality
      information was collected during massage or resting and the following night. We
      found that the total PSQI was significantly decreased in the treatment group
      following the aromatherapy massage. Specifically, the components such as
      subjective sleep quality, sleep disturbance, and daytime dysfunction were
      significantly decreased. However, there were no significant changes of average
      PSQI scores between the two groups before and after intervention. Taken together,
      our study suggested that aromatherapy massage could improve sleep quality of
      nurses with monthly rotating night shift.

PMID- 28761498
TI  - Tranquilizing and Allaying Excitement Needling Method Affects BDNF and SYP
      Expression in Hippocampus.
AB  - Sleep disorder is a state of sleep loss caused by various reasons, which leads to
      a series of changes, such as emotion, learning and memory, and immune function.
      "Tranquilizing and allaying excitement" was widely used in clinical treatment of
      insomnia; however, the mechanism was still not very clear. We randomly divided
      rats into three groups: control group, sleep deprivation group, and acupuncture
      treatment group. We observed BDNF and SYP expression in hippocampus in these
      three groups. Both protein contents and mRNA contents of BDNF and SYP were
      measured by western blot, immunohistochemistry, and RT-PCR analysis. The sleep
      deprivation model was established using modified multiple platform sleep
      deprivation method (MMPM). Our study explored the BDNF and SYP abnormality in
      hippocampus caused by sleep deprivation and "tranquilizing and allaying
      excitement" intervention regulated the abnormal expression of BDNF and SYP caused
      by sleep deprivation on the short run and the long run. Our study provided a
      molecular evidence that "tranquilizing and allaying excitement" treatment in rats
      with sleep disorder affects learning and memory ability.

PMID- 28761499
TI  - Anticancer Efficacy of Cordyceps militaris Ethanol Extract in a Xenografted
      Leukemia Model.
AB  - Cordyceps militaris is used widely as a traditional medicine in East Asia.
      Although a few studies have attempted to elucidate the anticancer activities of
      C. militaris, the precise mechanism of C. militaris therapeutic effects is not
      fully understood. We examined the anticancer activities of C. militaris ethanolic
      extract (Cm-EE) and its cellular and molecular mechanisms. For this purpose, a
      xenograft mouse model bearing murine T cell lymphoma (RMA) cell-derived cancers
      was established to investigate in vivo anticancer mechanisms. MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, immunoblotting
      analysis, and flow cytometric assay were employed to check in vitro cytotoxicity,
      molecular targets, and proapoptotic action of Cm-EE. Interestingly, cancer sizes
      and mass were reduced in a C. militaris-administered group. Levels of the
      phosphorylated forms of p85 and AKT were clearly decreased in the group
      administered with Cm-EE. This result indicated that levels of phosphoglycogen
      synthase kinase 3beta (p-GSK3beta) and cleaved caspase-3 were increased with
      orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of
      cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was
      significantly increased in a Cm-EE treated group compared with a control group.
      Our results suggested that C. militaris might be able to inhibit cancer growth
      through regulation of p85/AKT-dependent or GSK3beta-related caspase-3-dependent
      apoptosis.

PMID- 28761500
TI  - Predicting Factors of Depression, Antidepressant Use and Positive Response to
      Antidepressants in Perinatal and Postpartum Women.
AB  - BACKGROUND: In the United States, there is a disparity in knowledge of nationwide
      depression prevalence, the antidepressant use and the antidepressant responses
      during perinatal/postpartum periods. OBJECTIVE: This study investigated the
      predicting factors of depression, antidepressant use and positive antidepressant
      response during the perinatal/postpartum periods. METHOD: The 2007-2012 National
      Health and Nutrition Examination Surveys (NHANES) were combined to identify adult
      pregnant women, those within the 18-month postpartum period (n=492) and their
      depression statuses via demographics, health care accessibility, antidepressant
      use and illicit drug use information. The characteristics of different study
      groups were compared (depression versus no-depression groups, antidepressant
      users versus non-antidepressant users, and antidepressant responders versus
      antidepressant non-responders). Multivariable logistic regression analysis was
      used to predict factors of perinatal depression (PND)/ postpartum depression
      (PPD), antidepressant use and antidepressant positive response in PND/PPD.
      RESULTS: PND/PPD individuals had higher rates of mental health visits. No
      predicting factor for developing PND/PPD was shown. Antidepressant users were
      significantly older with insurance and recent health checkups/ mental visits.
      Being below the poverty level and having some health care accessibility are
      predictors for being on antidepressants. Recent non-illicit drug use is a
      predictor for PND/PPD symptom improvement while on antidepressants. CONCLUSION:
      The group of those with social-economic disadvantages was more likely to be on
      antidepressants for PND/PPD. Illicit drug users were less likely to show
      improvement with antidepressants. The safety and efficacy of antidepressant use
      during this period is controversial. More studies need to focus on the barriers
      involving antidepressant treatments, the safety and outcomes of antidepressants
      for PND/PPD management.

PMID- 28761501
TI  - Threshold Dynamics of a Stochastic SIR Model with Vertical Transmission and
      Vaccination.
AB  - A stochastic SIR model with vertical transmission and vaccination is proposed and
      investigated in this paper. The threshold dynamics are explored when the noise is
      small. The conditions for the extinction or persistence of infectious diseases
      are deduced. Our results show that large noise can lead to the extinction of
      infectious diseases which is conducive to epidemic diseases control.

PMID- 28761502
TI  - Psychiatric disorders in low backache patients: A neurosurgeon's nightmare!!!

PMID- 28761503
TI  - There is no evidence that laminoplasty results in improved outcomes compared with
      laminectomy in cervical spinal cord injury without instability.

PMID- 28761504
TI  - Comments for radiological study of C3-C4 level surgical cases of cervical
      spondylosis.

PMID- 28761505
TI  - A case of early extraneural medulloblastoma metastases in a young adult.

PMID- 28761506
TI  - Evidence-based evaluation of early versus late surgical decompression in cervical
      spinal cord injury.

PMID- 28761507
TI  - Primary intracranial dural-based Ewing sarcoma/peripheral primitive
      neuroectodermal tumor mimicking a meningioma: A rare tumor with review of
      literature.
AB  - Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) is a
      malignant small, round cell tumor arising from bone and soft tissue in children
      and young adults. It can occur at osseous and extraosseous sites. Its usual
      locations are diaphysis of long bones followed by pelvis, ribs, vertebrae, and
      rarely skull. We reviewed the literature and PubMed advanced search on ES/pPNET
      occurring at extraosseous sites, mainly involving the central nervous system
      (CNS). We reported a case of a 22-year-old male presenting with seizure finally
      diagnosed as a case of ES/pPNET. The challenges in management of this rare CNS
      tumor and its differential diagnosis are highlighted. We found that most cases of
      ES involving CNS represent secondary metastases from extracranial sites of
      ES/pPNET and there are rare case reports of primary intracranial ES-pPNET.
      Furthermore, among these intracranial tumors, most common tumors occupy an
      intraaxial location and only a handful of cases of dural-based or extraaxial
      tumors mimicking meningioma are reported. Differentiation of pPNET from central
      PNET (cPNET) is important as it has definitive therapeutic and prognostic
      implications. Awareness of this entity of ES/pPNET, its rare dural presentation,
      and differentiation from the more common cPNET is needed for appropriate patient
      management. Meningeal ES/pPNET has to be kept in mind in the differential
      diagnosis of meningeal tumors eroding bone.

PMID- 28761508
TI  - Sphenoid wing en plaque meningioma development following craniopharyngioma
      surgery and radiotherapy: Radiation-induced after three decades.
AB  - Radiation therapy is widely used as adjuvant or primary treatment modality of
      neoplastic lesions. Radiation therapy may cause an acute adverse effect such as
      brain edema, radiation necrosis, or delayed, for example, panhypopituitarism,
      vasculitis, and rare de-novo neoplasm development. However, radiation-induced
      meningioma (RIM) occurrence is extremely rare. A detailed PubMed and Medline
      search yielded only three isolated Case-reports of RIM development in
      craniopharyngioma cases receiving radiotherapy after surgery. All cases occurred
      in patients < 13-year age, with male preponderance, detected after a mean
      interval of 23-year, the range being 2-44 years. Two had solitary while the third
      had multiple meningiomas. Authors report an 8-year-old female, who was operated
      for craniopharyngioma and received adjuvant therapy, was asymptomatic for next 30
      years, met a road traffic accident and magnetic resonance imaging brain revealed
      incidental right sphenoid wing en plaque meningioma. She was planned for gamma
      knife therapy as unwilling for surgical intervention. Management of RIM
      development after radiotherapy of craniopharyngioma along with pertinent
      literature is reviewed briefly.

PMID- 28761510
TI  - A systematic review about the position-related complications of acoustic neuroma
      surgery via suboccipital retrosigmoid approach: Sitting versus lateral.
AB  - This systematic review wasdesigned to compare the complications of acoustic
      neuroma surgery via the suboccipital retrosigmoid approach in the sitting versus
      lateral positions. Searches for randomized trials and observational studies about
      the complications of acoustic neuroma surgery were performed in five medical
      databases (though October 2015) including PubMed, MEDLINE (In-Process and Other
      Non-Indexed Citations), EMBASE, Cochrane Central Register of Controlled Trials
      (CENTRAL) and PsycINFO. Primary outcomes in this study were venous air emboli,
      neuropsychological defects, CSF leak, facial and abducens nerves palsy,
      postoperative deafness, hydrocephalus and mortality. Secondary outcomes were
      total tumor removal, facial and cochlear nerves preservation and ataxia. 843
      abstracts and titles were reviewed and 10 studies (two non-randomized comparative
      studies and 8 non-comparative case series) were included for data extraction.
      Because of the heterogeneity of the studies, small number of participants and
      methodological shortcomings, findings were evaluated qualitatively. No impressive
      advantage was found in surgical or neurological outcomes for use of the sitting
      or lateral positions in patients with acoustic neuroma surgery. According to the
      available evidence, it seems that both sitting and lateral positions can be used
      with an equivalent safety for acoustic neuroma surgery via the retrosigmoid
      suboccipital approach. There seems a clear need for comparative studies to
      compare harms and other outcomes for these two positions.

PMID- 28761509
TI  - Newer insights to pathogenesis of traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a silent epidemic and a global burden. However,
      when it comes to advancement in our quest to managing patients with head
      injuries, we seem to be making circles rather than moving forward. In this review
      paper, we focus on the current understandings in the pathogenesis of TBI that may
      aid us in providing newer avenues in management of the same.

PMID- 28761511
TI  - Genetic associations of intracranial aneurysm formation and sub-arachnoid
      hemorrhage.
AB  - Risk factors for cerebral aneurysms typically include age, hypertension, smoking,
      and alcohol usage. However, the possible connection of aneurysms with genetic
      conditions such as Marfan's syndrome, polycystic kidney disease, and
      neurofibromatosis raises the question of possible genetic risk factors for
      aneurysm, and additionally, genetic risk factors for rupture. We conducted a
      literature review using the PubMed database for studies regarding genetic
      correlation with cerebral aneurysm formation as well as rupture from December
      2008 to Jun 2015. Twenty-one studies related to IA formation and 10 concerning IA
      rupture that met our criteria were found and tabulated. The most studied gene and
      the strongest association was 9p21/CDKN2, which is involved in vessel wall
      remodelling. Other possible genes that may contribute to IA formation include
      EDNRA and SOX17; however, these factors were not studied as robustly as CDKN2.
      Multiple factors contribute to aneurysm formation and rupture and the
      contributions of blood flow dynamics and comorbidities as mentioned previously,
      cannot be ignored. While these elements are important to development and rupture
      of aneurysms, genetic influence may predispose certain patients to formation of
      aneurysms and eventual rupture.

PMID- 28761512
TI  - Surgical treatment of large and giant cavernous carotid aneurysms.
AB  - Cavernous carotid aneurysms (CCAs) are uncommon pathologic entities. Extradural
      place and the skull base location make this type of an aneurysm different in
      clinical features and treatment techniques. Direct aneurysm clipping is
      technically difficult and results in a significant postoperative neurological
      deficit. Therefore, several techniques of indirect surgical treatment were
      developed with different surgical outcomes, such as proximal occlusion of
      internal carotid artery (ICA) or trapping with or without bypass (superficial
      temporal artery-middle cerebral artery bypass or high-flow bypass). High-flow
      bypass with proximal ICA occlusion seems to be the most appropriate surgical
      treatment for CCA because of the high rate of symptom improvement, aneurysm
      thrombosis, and minimal postoperative complications. However, in cases of CCA
      presented with direct carotid-cavernous fistula, the appropriate surgical
      treatment is high-flow bypass with aneurysm trapping, which the fistula can be
      obliterated immediately after surgery.

PMID- 28761513
TI  - Outcomes following surgical management of cervical chordoma: A review of
      published case reports and case series.
AB  - AIM: This review aimed to summarize the clinical outcomes in relation to tumor
      resection margins of cervical chordomas. METHODS: Studies that described any
      surgical intervention for cervical chordoma were identified. Cervical chordomas
      with cranial or spinal extension, purely retropharyngeal chordomas or where
      resection type was not reported, were excluded from the study. RESULTS: Seventy
      six articles were obtained and these reported a total of 195 patients. Seventy
      six percent cervical chordoma patients had intralesional resection with adjuvant
      radiotherapy. Ninety-two percent chordoma recurrences and all chordoma metastases
      occurred in patients with intralesional resection. En bloc surgeries were longer
      (900 min vs. 619 min) and staged surgeries. Intralesional surgeries (2899 ml vs.
      2661 ml) had greater intraoperative blood loss. Vertebral artery and nerve root
      sacrifice were greater in en bloc patients (35%, 39%) compared to intralesional
      patients (17%, 10%). Postoperative complications were more common in en bloc
      (54%) than in intralesional patients (11%). CONCLUSIONS: En bloc resection
      cervical chordomas are associated with less recurrence and no metastasis compared
      to intralesional resection. En bloc is possible through wide exposure of the
      vertebrae via a multidisciplinary team approach and utilization of particular
      surgical equipment. The higher rate of complications associated with en bloc
      surgeries may be acceptable, particularly when there is a chance of cure of
      disease.

PMID- 28761514
TI  - Microsurgical management of benign lesions interior to the cavernous sinus: A
      case series.
AB  - BACKGROUND: Benign lesion interior to the cavernous sinus (CS) is very rare.
      OBJECTIVE: In this series we found nonneoplastic lymphatic aggregation and
      osteoclastoma inside the CS which is very rare and probably not reported in
      literature. One interesting postoperative complaint of feeling of tickling down
      of warm water under the skin forehead was found in the patient of inflammatory
      disease of CS which is not reported in literature. Here we also describe our
      experiences of microsurgical management of series of benign lesions inside the
      CS. MATERIALS AND METHODS: Benign mass originated from the content of CS or inner
      side of walls of CS, confirmed peroperatively were included in this series.
      Prospectively recorded data of microsurgical management was retrogradely studied.
      RESULTS: Total number of patient was 12. Patient's age range was 30-60 years.
      Follow-up range was 60 months to 19 months. Three was nonneoplastic lesion
      (tuberculosis, inflammatory and nonneoplastic lymphoid infiltration). Among the 9
      neoplastic lesions, two hemangiomas, two meningiomas, three 6th nerve
      schwannomas, one osteoclastoma and one epidermoid tumor. Middle cranial fossa
      subtemporal extradural approach was used in 9 cases and in two cases extended
      middle fossa zygomatic approach. New postoperative 3rd nerve palsy developed in 5
      cases all recovered completely except one. In seven patients 6th nerve palsy
      developed after operation; only one recovered. Postoperatively simultaneous 3rd,
      4th and 6th nerve palsy developed in four cases. One interesting postoperative
      complaint of feeling of tickling down of warm water under the skin of left sided
      forehead was found in the patient of inflammatory disease of CS. Mortality was
      nil. Total resection was done in 9 cases. There was no recurrence till last
      follow-up. CONCLUSION: Though decision for microsurgical removal of such lesions
      is not straight forward. Probably microsurgery is the best option in treating
      such benign lesions though it may associate with some permanent cranial nerve
      palsy.

PMID- 28761515
TI  - Commentary.

PMID- 28761516
TI  - Surgical management of giant skull osteomas.
AB  - OBJECTIVE: Surgical management of giant skull osteomas Osteomas are benign,
      generally slow growing, bone forming tumors limited to the craniofacial and jaw
      bones. MATERIALS AND METHODS: A retrospective review of all cases of osteoma
      diagnosed from 2009 to 2013 treated in our hospital. The data collected included
      age at diagnosis, gender, lesion location, size, presenting and duration of
      symptoms, treatment, complication and outcome. RESULTS: During our study period
      there were 15 cases that were treated surgically. Their mean age was 42 years
      (range: 15-65 years) and all of our patients were female. The average duration of
      symptoms was 3 years and size varying from 4 cm to 12 cm. Eight patients
      complained of headache, whereas 6 patients complained about esthetics, and 1
      patient presented with proptosis. The tumor was excised by cutting the base of
      the tumor and then residual tumor was grinded using a round head cutting bar.
      Osteoma was removed with esthetically acceptable appearance. CONCLUSION: There
      were no major complications during operative and postoperative period. Although
      osteomas are usually slow growing but surgery is usually performed due to
      esthetic reasons. It is important to plan an appropriate surgical approach that
      minimizes any damage to the adjacent structures.

PMID- 28761517
TI  - Role of routine repeat computed tomography of brain in patients with mild and
      moderate traumatic brain injury: A prospective study.
AB  - BACKGROUND: Computed tomography (CT) has become the primary investigative
      modality for traumatic brain injury (TBI) and there are established guidelines
      for the initial CT (CT-1). There are no specific guidelines for scheduling repeat
      CT in TBI. This study was carried out to compare the usefulness of unscheduled
      repeat CT (UCT-2) with scheduled repeat CT (SCT-2) in the presence or absence of
      neurological deterioration and to identify risk factors associated with
      radiological worsening (RW). METHODS: This prospective study comprised admitted
      patients with mild and moderate TBI between February and May, 2014 and all
      patients were subjected to repeat CT brain. Patients with penetrating brain
      injuries and surgical conditions after CT-1, and age < 5 years were excluded.
      Positive yield after the second CT (SCT-2 and UCT-2) leading to modification of
      management were compared between the two groups. RESULTS: In this study, 214
      patients (214/222) underwent SCT-2 and 8 underwent UCT-2 (8/222). Surgery was
      required in 2 (0.9%) from the first group and 7 (87.5%) in the latter. UCT-2 was
      more likely to show RW warranting surgery as compared to SCT-2 (P < 0.05). In the
      SCT-2 group, CT-1 had been done within 2 h after trauma in 30 patients and 8
      (8/30; 26.7%) showed RW and; after 2 h in the remaining 184 (184/214) with RW
      seen in 23 (23/184; 12.5%). RW was more common when the CT-1 was within 2 h from
      trauma (P < 0.05). In our study, the age of the patient and admission Glasgow
      Coma Scores did not significantly affect the findings in repeat CT. CONCLUSION:
      Repeating CT brain is costly besides needing significant logistical support to
      shift an injured and often unstable patient. SCT-2 is more likely to show RW when
      CT-1 is done within 2 h after trauma. UCT-2 is more likely to show RW and
      findings warranting surgery as compared to SCT-2. Hence, a repeat CT may be
      preferred only in the presence of clinical worsening and when CT-1 is done within
      2 h after trauma.

PMID- 28761518
TI  - Factors affecting outcome of acute cervical spine injury: A prospective study.
AB  - BACKGROUND: Injury to the spine and spinal cord is one of the common cause of
      disability and death. Several factors affect the outcome; but which are these
      factors (alone and in combination), are determining the outcomes are still
      unknown. The aim of the study was to evaluate the factors influencing the outcome
      following acute cervical spine injury. MATERIALS AND METHODS: A prospective
      observational study at single-center with all patients with cervical spinal cord
      injury (SCI), attending our hospital within a week of injury during a period of
      October 2011 to July 2013 was included for analysis. Demographic factors such as
      age, gender, etiology of injury, preoperative American Spinal Injury Association
      (ASIA) grade, upper (C2-C4) versus lower (C5-C7) cervical level of injury,
      imageological factors on magnetic resonance imaging (MRI), and timing of
      intervention were studied. Change in neurological status by one or more ASIA
      grade from the date of admission to 6 months follow-up was taken as an
      improvement. Functional grading was assessed using the functional independence
      measure (FIM) scale at 6 months follow-up. RESULTS: A total of 39 patients with
      an acute cervical spine injury, managed surgically were included in this study.
      Follow-up was available for 38 patients at 6 months. No improvement was noted in
      patients with ASIA Grade A. Maximum improvement was noted in ASIA Grade D group
      (83.3%). The improvement was more significant in lower cervical region injuries.
      Patient with cord contusion showed no improvement as opposed to those with just
      edema wherein; the improvement was seen in 62.5% patients. Percentage of
      improvement in cord edema <=3 segments (75%) was significantly higher than edema
      with >3 segments (42.9%). Maximum improvement in FIM score was noted in ASIA
      Grade C and patients who had edema (especially <=3 segments) in MRI cervical
      spine. CONCLUSIONS: Complete cervical SCI, upper-level cervical cord injury,
      patients showing MRI contusion, edema >3 segments group have worst improvement in
      neurological status at 6 months follow-up.

PMID- 28761519
TI  - Comparison of postoperative clinical outcome after repairing surgery for lumbar
      spinal stenosis between diabetic and nondiabetic patients.
AB  - BACKGROUND: Poorer postoperative outcome is suggested after repairing surgery in
      diabetic patients with lumbar spinal stenosis in comparison with nondiabetic
      patients. The present study aimed to compare the clinical outcome of surgery for
      lumbar spinal stenosis and diabetic and nondiabetic patients to highlight the
      effect of diabetes on prognosis of this surgical procedure. METHODS: This
      prospective cohort study is conducted on 25 diabetic patients with lumbar spinal
      stenosis who were candidate for surgical treatment. A gender, age, and body mass
      index-matched group including 30 nondiabetic patients with lumbar spinal stenosis
      was considered as the control. The clinical condition of the patients was
      assessed based on oswestry disability index (ODI) before and immediately after
      surgery. RESULTS: There was no difference in baseline ODI index between diabetes
      and diabetes group (73.68 +/- 18.89 vs. 71.20 +/- 18.27, P = 0.625), whereas
      postprocedure ODI was significantly higher in diabetic patients than in
      nondiabetic group (54.32 +/- 19.03 vs. 29.47 +/- 18.75, P < 0.001). The
      multivariable logistic regression analysis could show a difference in
      postoperative ODI between diabetic and nondiabetic patients with the presence of
      baseline variables as the confounders (beta = -24.509, P < 0.001). CONCLUSION:
      Lower improvement in physical ability is expected in diabetic patients after
      surgery for lumbar spinal stenosis when compared to nondiabetes patients.

PMID- 28761520
TI  - Computed tomographic study of posterior cranial fossa, foramen magnum, and its
      surgical implications in Chiari malformations.
AB  - OBJECTIVE: The aim of this study is to measure the height and volume of the bony
      part of the posterior cranial fossa (PCF) and the surface area of the foramen
      magnum (FM) using computed tomography (CT) scans and to correlate our clinical
      findings with the available current literature. MATERIALS AND METHODS: This cross
      sectional study was conducted in a tertiary care referral hospital in the
      Southern part of India during the period from January 2015 to August 2015. A
      total of 100 CT scans of the suspected head injury patients were collected
      retrospectively form the basis for this study. The height, volume of PCF and the
      anteroposterior (AP), transverse diameter, and surface area of the FM were
      measured. The values of all parameters were subjected to statistical analysis
      using SPSS version 16. RESULTS: The age of the patients were ranged between 18
      and 70 years with the mean age of 41.22 +/- 13.93 years. The dimensions of the
      posterior fossa and FM were larger in males compared to females. The mean height
      of the posterior fossa was 38.08 (+/-4.718) mm (P = 0.0001), and the mean volume
      of the posterior fossa was 157.23 (+/-6.700) mm3 (P = 0.0001). The mean AP,
      transverse diameter, and the surface area of the FM were 33.13 (+/- 3.286) mm,
      29.01 (+/- 3.081) mm, and 763.803 (+/-138.276) mm2, respectively. CONCLUSION: The
      normal dimensions of the posterior fossa and FM were less in females than males
      and were useful to radiologists and neurosurgeons to better their diagnostic
      inferences, as well as to determine the proper treatment options in Chiari
      malformation type I (CMI) and other posterior fossa anomalies. The posterior
      fossa tissue volume can be reliably measured in patients with CMI using our
      method. More studies were required because there were variations in dimensions
      among individuals of different races in different regions of the world.

PMID- 28761521
TI  - Safety and efficacy of spinal loop rectangle and sublaminar wires for
      osteoporotic vertebral compression fracture fixation.
AB  - BACKGROUND: Natural history of osteoporotic vertebral compression fractures
      (OVCFs), that is, collapse, loads the rigid pedicle screw rod construct in the
      absence of anterior column reconstruction, often leading to implant back outs.
      Semi rigid spinal loop rectangle and sublaminar wire construct allows controlled
      axial collapse and does not require anterior column reconstruction. MATERIALS AND
      METHODS: This is a retrospective study of 50 consecutive patients of OVCFs. The
      immediate and final follow-up safety (neurologic deficit, implant failure/back
      out, revision surgeries, and infection) and efficacy (visual analog scale [VAS]
      score, axial collapse of the fracture, fracture union and retaining, and the
      attempted segmental deformity correction) parameters were compared to describe
      the utility of spinal loop rectangle and sublaminar wiring as a novel, low cost
      modality of spinal instrumentation for treating OVCFs. RESULTS: All the twelve
      patients with Frankel grade D neurologic deficit improved to Frankel grade E and
      six patients (out of 8) with Frankel grade C improved to Frankel grade E (and
      remaining two patients improved to Frankel grade D), following surgery. The
      average preoperative VAS score of 8.98 (ranging from 5 to 10) improved to 2.76
      (ranging from 1 to 10) at final follow-up. Controlled collapse of anterior
      column, union of OVCF nonunion, and retaining of attempted deformity correction
      by sublaminar wire anchors cephalad and caudal to the transpedicular
      decompression was seen in each patient at the final follow-up. CONCLUSION: Spinal
      loop rectangle and sublaminar wiring construct are viable alternative options for
      stabilizing OVCFs.

PMID- 28761522
TI  - Outcome and management of spinal tuberculosis according to severity at a tertiary
      referral center.
AB  - OBJECTIVE: Anti-tuberculosis (TB) treatment remains the mainstay of treatment of
      spinal TB. There is a lack of consensus regarding the timing of interventional
      procedures and surgery in the patients with spinal TB. This study aims to
      prospectively study the clinical outcome and management in patients presenting
      with spinal TB at our tertiary referral center and teaching hospital. METHODS:
      Data were collected prospectively from 48 patients treated for spinal TB
      presenting to us from August 2011 to December 2012. All the patients were
      followed-up for the duration of anti-TB treatment. RESULTS: The categorization of
      patients into different management groups was based on the clinical and
      radiological findings at the time of diagnosis. The patients with mild disease (n
      = 23) were successfully managed with anti-TB treatment alone. The other 25
      patients needed an intervention either in the form of pigtail catheter drainage
      of the paravertebral collection (n = 18) or an extensive surgical debridement
      followed by the fusion techniques (n = 7). All the patients responded well to the
      treatment, and there were no significant complications in any of the patients. It
      had been observed that various stages of spinal TB demand different approaches
      for the treatment in the form of either chemotherapy alone, chemotherapy with
      pigtail drainage of the paravertebral collection, or surgery in conjunction with
      chemotherapy. CONCLUSIONS: Judicious use of pigtail drainage and surgical
      intervention in addition to anti TB treatment can be rewarding in the patients
      with spinal TB.

PMID- 28761523
TI  - The use of event-related potential (P300) and neuropsychological testing to
      evaluate cognitive impairment in mild traumatic brain injury patients.
AB  - BACKGROUND: The aim of the study is to compare the amplitude and latency of the
      P300 event-related potential (ERP) component between a control group and patients
      after mild traumatic brain injury (mTBI) during 1-7 days (short duration) and 2-3
      months (long duration), and to compare the outcome of neuropsychological tests
      between the long duration postinjury and control study groups. MATERIALS AND
      METHODS: We studied responses to auditory stimulation in two main and one
      subgroups, namely the control healthy group (19 patients, both ERP and
      neuropsychology test done), the mTBI 1 group (17 patients, only ERP done within 7
      days after injury), and the mTBI 2 subgroup (the 17 mTBI 1 patients in whom a
      repeated ERP together with neuropsychological testing was done at 2-3 months
      postinjury). Auditory evoked responses were studied with two different stimuli
      (standard and target stimuli), where the P300 amplitude and latency were recorded
      from three midline sites and results were compared between the groups, as were
      the neuropsychological test results. RESULTS: There was a significant
      prolongation of the target P300 latency values shown by the MBI 1 group measured
      at the central electrode when compared to the control group, which was also seen
      when the mTBI 1 and mTBI 2 groups were compared. The results of the P300
      amplitude values measured at the frontal electrode showed the control group to
      have higher readings during the presentation of standard tones when compared to
      the mTBI 1 group. The mTBI 2 group performed better on some neuropsychological
      tests. CONCLUSION: The latency of P300 was significantly prolonged in early mTBI
      patients who improved over time, and the neuropsychological testing on mTBI 2
      patients showed them to be comparable to the control group. The study indicates
      that ERP should be used as an additional modality of investigation in mTBI
      patients.

PMID- 28761524
TI  - Selective dorsal rhizotomy: A multidisciplinary approach to treating spastic
      diplegia.
AB  - BACKGROUND: Spasticity is a motor disorder that interferes with mobility and
      affects the quality of life. Different approaches have been utilized to address
      patients with spastic diplegia, among which is selective dorsal rhizotomy (SDR).
      Although SDR has been shown to be efficacious in treating spastic patients, many
      neurologists and neurosurgeons are not well aware of the procedure, its
      indications, and expected outcomes due to the limited number of centers
      performing this procedure. OBJECTIVES: The aim of this study is to describe the
      collaborative multidisciplinary approach between neurosurgeons,
      neurophysiologists, and physiotherapists in performing SDR. In addition, we
      delineate three illustrative cases in which SDR was performed in our patients.
      MATERIALS AND METHODS: A retrospective review and analysis of the clinical
      records of our three patients who underwent SDR was conducted and reported.
      Patients' outcomes were evaluated and compared to preoperative measurements based
      on clinical examination of power, tone (Ashworth scale), gait, and range of
      motion, as well as subjective functional assessment, gross motor function
      classification system, and gross motor function measure with follow-up at 6, 12,
      and 24 months postoperatively. A detailed description of our neurosurgical
      technique in performing SDR in collaboration with neurophysiology and
      physiotherapy monitoring is provided. RESULTS: The three patients who underwent
      SDR using our multidisciplinary approach improved both functionally and
      objectively after the procedure. No intraoperative or postoperative complications
      were encountered. All patients were doing well over a long postoperative follow
      up period. CONCLUSION: A multidisciplinary approach to treating spastic diplegia
      with SDR can provide good short-term and long-term outcomes in select patients
      suffering from spastic diplegia.

PMID- 28761525
TI  - The minipterional approach for ruptured and unruptured anterior circulation
      aneurysms: Our initial experience.
AB  - OBJECTIVE: To report our experience with the minipterional (MPT) craniotomy
      approach for anterior circulation aneurysms and to discuss the clinical outcomes
      as well as to evaluate the advantages of this unique approach. MATERIALS AND
      METHODS: Single-center retrospective review of 57 cases involving anterior
      circulation aneurysms both ruptured and unruptured aneurysms treated with the
      MPT. We analyzed the clinical and patient demographic data, aneurysm
      characteristics, surgical outcomes, and complications in these individuals.
      RESULTS: Between July 2008 and March 2014, of the 57 patients reviewed: 45 had
      middle cerebral artery (MCA), 6 had internal carotid artery terminus, and 7 had
      posterior communicating artery aneurysms. 20 of the 57 patients presented with a
      ruptured aneurysm. The average aneurysm size was 5.8 mm. The length of
      hospitalization for unruptured aneurysm cases ranged between 3 and 5 days. The
      average follow-up for all cases was 21.5 months. Successful clipping of the
      aneurysms was obtained in all patients. None of the cases required additional
      skin incisions or craniotomy extensions. The overall surgical outcomes were
      favorable. There was no postoperative facial nerve damage, temporalis muscle
      wasting, or symptoms of paresthesias around the incision line. Two patients
      developed a postoperative stroke manifested as symptoms of unilateral arm and
      facial weakness, receptive aphasia, and dysarthria. CONCLUSION: The MPT provides
      a reliable and less invasive alternative to the standard pterional craniotomy.
      Furthermore, ruptured and unruptured anterior circulation aneurysms can safely
      and effectively be treated with limited bone removal which provides better
      cosmetic outcomes and excellent postoperative temporalis muscle function.

PMID- 28761526
TI  - A study of partial pressure of arterial carbon dioxide and end-tidal carbon
      dioxide correlation in intraoperative and postoperative period in neurosurgical
      patients.
AB  - BACKGROUND AND AIM: Monitoring carbon dioxide (CO2) is of utmost importance in
      neurosurgical patients. It is measured by partial pressure of arterial CO2
      (PaCO2) and end-tidal CO2 (ETCO2). We aimed to study the correlation between
      PaCO2 and ETCO2 in neurosurgical patients in the intraoperative and postoperative
      period on mechanical ventilation in Postanesthesia Care Unit (PACU). METHODOLOGY:
      This was prospective observational study done at tertiary care teaching public
      hospital over a period of 1 year. We studied 30 patients undergoing elective
      craniotomy intraoperatively and in the postoperative period on mechanical
      ventilation for 24 h. Serial measurement of ETCO2 and PaCO2 at baseline, hourly
      intraoperatively and every 6 hourly in the PACU were studied. Data analysis was
      done using SPSS software version 20. RESULTS: The mean PaCO2-ETCO2 gradient
      intraoperatively over 4 h is 3.331 +/- 2.856 and postoperatively over 24 h is
      2.779 +/- 2.932 and lies in 95% confidence interval. There was statistically
      significant correlation between PaCO2 and ETCO2 intraoperatively baseline, 1 h, 2
      h, 3 h, and 4 h with Pearson's correlation coefficients of 0.799, 0.522, 0582,
      0.439, and 0.547, respectively (P < 0.05). In PACU at baseline, 6 h, 12 h, 18 h,
      and 24 h Pearson's correlation coefficients were. 534, -0.032, 0.522, 0.242,
      0.592, and 0.547, respectively, which are highly significant at three instances
      (P < 0.01). CONCLUSION: ETCO2 correlates PaCO2 with acceptable accuracy in
      neurosurgical patients in the intraoperative and postoperative period on
      mechanical ventilation in Intensive Care Unit. Thus, continuous and noninvasive
      ETCO2 can be used as a reliable guide to estimate arterial PCO2 during
      neurosurgical procedures and in PACU.

PMID- 28761528
TI  - Multiloculated hydrocephalus.

PMID- 28761527
TI  - The benefits of navigated neuroendoscopy in children with multiloculated
      hydrocephalus.
AB  - CONTEXT: Multiloculated hydrocephalus remains one of the most challenging
      neurosurgical problems. In this study, we use frameless navigation during
      endoscopic interventions to improve the efficiency of operations. SUBJECTS AND
      METHODS: Nine navigated endoscopic procedures were performed in 8 children with
      various forms of multiloculated hydrocephalus from March 2013 to June 2014.
      Preoperatively, the optimal entry point for fenestration of several cysts was
      determined on the basis of magnetic resonance data. During surgery, rigid
      endoscope was registered in neuronavigation system for making the connection
      between separated ventricles and cysts. The final stage of the operation was to
      conduct a stent through the working channel of the endoscope for implantation of
      a shunt. RESULTS: Number of compartments interconnected by an operation ranged
      from 3 to 5. Seven interventions were performed simultaneously with the shunt
      implantation. The follow-up period ranged from 9 to 15 months. The clinical
      improvement as a result of the operation was achieved in all children. The follow
      up included clinical examination and evaluation of magnetic resonance imaging.
      Additional surgery was necessary in two patients: The first 5 months later, the
      second 1-year after endoscopic intervention. CONCLUSION: Application of frameless
      navigated neuroendoscopy makes this kind of operations the most efficient and
      safe for the patient.

PMID- 28761529
TI  - Severity of anemia and hemostatic parameters are strong predictors of outcome in
      postoperative neurosurgical patients.
AB  - OBJECTIVE: Post-operative neurosurgical patients are commonly associated with
      haemostatic derangements; many a times leading to development of overt
      disseminated intravascular coagulation (DIC) and eventually death in some of
      them. The present study has analysed the factors that would predict the outcome
      in post operative neurosurgical patients with deranged haemostatic parameters.
      METHODS: This is a prospective, descriptive study over a period of 15 months on
      115 post operative neurosurgical patients who were clinically suspected to have
      DIC and investigated for the haemostatic parameters. Patients with at least one
      parameter abnormal were included in the study and complete data was available in
      85 patients was analysed. RESULTS: Majority of deaths (22/33, 66.7%) were related
      to bleeding and end organ failure attributed to DIC. The most common haemostatic
      abnormalities found were thrombocytopenia with prolonged Prothrombin time (PT) in
      48/115 (42.7%) patients. The parameters found significantly different between
      those who survived and those died were age, post-operative development of chest
      infections, severe anemia, and renal function abnormalities. Also, patient
      outcome correlated strongly with marked prolongation of prothrombin time (PT) and
      Partial thromboplastin time (PTT). However, presence of >=3 coagulation
      abnormalities, presence of significant drop in haemoglobin post operatively and
      /or development of chest infection predicted death in postoperative neurosurgical
      patients with accuracy of 80.4% and this was highly significant (P = 0.000).
      CONCLUSION: Presence of >=3 coagulation abnormalities, significant drop in
      hemoglobin post operatively and /or development of chest infection post
      operatively were strong predictors of death in postoperative neurosurgical
      patients.

PMID- 28761530
TI  - Contribution of the xenograft bone plate-screw system in lumbar transpedicular
      stabilization: An in vivo study in dogs.
AB  - OBJECTIVES: Xenograft bone plate-screws (XBPSs) can be alternative tools in
      lumbar transpedicular stabilization (TS). The aim of this study was to show
      biomechanical and histopathological contribution of the XBPSs system in lumbar
      TS. MATERIALS AND METHODS: Fifteen (n = 15) hybrid dog and ten (n = 10) L2-4
      cadaveric specimens were included in the study. The dogs were separated according
      to surgical techniques: L3 laminectomy and bilateral facetectomy (LBF) in Group I
      (experimental group [EG I] (n = 5), L3 LBF plus TS with metal plate-screws (MPSs)
      in Group II (EG II) (n = 5), and L3 LBF plus TS with XBPSs in Group III (EG III)
      (n = 5). The cadaveric specimens were separated to L2-4 intact in Group I (CG I),
      (n = 5), and L3 LBF in Group II (CG II), (n = 5). The dogs were sacrificed at the
      end of 3rd month, and their L2-4 spinal segments were en bloc removed and
      prepared as in control groups. Flexion, extension, left-right bending, rotation,
      and compression tests were applied to all segments. Stiffness values were
      calculated and analyzed statistically. All dog segments were evaluated
      histopathologically. RESULTS: XBPS system showed a higher average stiffness
      values for left bending, extension, flexion, and compression compared to MPS, but
      these differences were not statistically meaningful. XBPS system had superiority
      to the fusion formation, as well. CONCLUSIONS: XBPSs provide stability and help
      the fusion formation, but this system does not have a biomechanical advantage
      over MPS system in TS.

PMID- 28761531
TI  - The role of tranexamic acid in prevention of hemorrhage in major spinal
      surgeries.
AB  - BACKGROUND: Blood loss that necessitates blood transfusion is one of the most
      frequent complications of major spinal surgeries. This study has been designed to
      evaluate the efficacy and safety of prophylactic tranexamic acid (TA) in
      decreasing perioperative blood loss. MATERIALS AND METHODS: From January to
      August 2011, all the patients who needed major spinal surgeries and aged between
      18 and 60-year-old were divided into two groups randomly, the experimental group
      received 10 mg/kg of TA 20 min after inducing the anesthesia as loading dose
      followed by 0.5 mg/kg/h until skin closure and the control group received equal
      amounts of normal saline as placebo. Intraoperative blood loss was recorded by
      estimating blood with the suction tube plus the number of bloody gasses. The
      amounts compared between the 2 groups and analyzed. RESULTS: Forty patients were
      enrolled in this study in the first group intraoperative, the 1st and 2nd
      postoperative days, the mean blood loss were 574 ml, 80.5 ml, and 669.5 ml while
      in the second group were 797 ml, 124 ml, and 921.5 ml. CONCLUSION: TA seems to be
      safe and can be considered in spinal surgeries with significant excepted blood
      loss especially in female patients and instrumental procedures. We suggest
      further studies on TAs efficacy and safety in larger scales.

PMID- 28761532
TI  - Skull base bony lesions: Management nuances; a retrospective analysis from a
      Tertiary Care Centre.
AB  - BACKGROUND: Skull base lesions are not uncommon, but their management has been
      challenging for surgeons. There is large no of bony tumors at the skull base
      which has not been studied in detail as a group. These tumors are difficult not
      only because of their location but also due to their variability in the
      involvement of important local structure. Through this retrospective analysis
      from a Tertiary Care Centre, we are summarizing the details of skull base bony
      lesions and its management nuances. MATERIALS AND METHODS: The
      histopathologically, radiologically, and surgically proven cases of skull base
      bony tumors or lesions involving bone were analyzed from the neurosurgery,
      neuropathology record of our Tertiary Care Institute from January 2009 to January
      2014. All available preoperative and postoperative details were noted from their
      case files. The extent of excision was ascertained from operation records and
      postoperative magnetic resonance imaging if available. RESULTS: We have
      surgically managed 41 cases of skull base bony tumors. It includes 11 patients of
      anterior skull base, 13 middle skull base, and 17 posterior skull base bony
      tumors. The most common bony tumor was chordoma 15 (36.6%), followed by fibrous
      dysplasia 5 (12.2%), chondrosarcoma (12.2%), and ewings sarcoma-peripheral
      primitive neuroectodermal tumor (EWS-pPNET) five cases (12.2%) each. There were
      more malignant lesions (n = 29, 70.7%) at skull base than benign (n = 12, 29.3%)
      lesions. The surgical approach employed depended on location of tumor and
      pathology. Total mortality was 8 (20%) of whom 5 patients were of histological
      proven EWS-pPNET. CONCLUSIONS: Bony skull base lesion consists of wide variety of
      lesions, and requires multispecialty management. The complex lesions required
      tailored approaches surgery of these lesions. With the advent of microsurgical
      and endoscopic techniques, and use of navigation better outcomes are being seen,
      but these lesions require further study for development of proper management
      plan.

PMID- 28761533
TI  - Outcome following surgical resection of craniopharyngiomas: A case series.
AB  - INTRODUCTION: Debate continues as to the optimum treatment for craniopharyngioma;
      radical surgical resection or partial resection followed by radiotherapy. Radical
      surgical resection may be complicated by intraoperative injury to surrounding
      structures and stormy postoperative hormonal problem. This study aims to examine
      the result of safe maximal surgical resection. MATERIALS AND METHODS:
      Retrospective study of all histopathologically proven craniopharyngiomas who had
      undergone surgical resection over an almost 8 year period was included. Data were
      collected reviewing demography, clinical presentation, hormonal dysfunction,
      extent of resection and visual deterioration. Outcome was measured in terms of
      Glasgow outcome scale and recurrence. RESULTS: Of 25 patients, 68% were male, and
      32% were female. Age of patients ranged from 7 to 58 years with a mean of 30.12
      +/- 16.42 years. Patients presented with visual deterioration were 76% and with a
      headache were 68%. Mean duration of symptoms was 10.64 +/- 14.28 months. Gross
      total resection was done in 21 (84%), while subtotal resection in 4 (16%) who
      also received subsequent adjuvant radiotherapy. During the postoperative period,
      diabetes insipidus developed in 84% patients, but none had it permanently.
      Favorable outcome was found in 88% patients. However, there were 4% operative
      mortality with overall mortality of 8% and tumor recurrence in 8% patients.
      CONCLUSION: Gross total excision if judiciously decided intraoperatively has a
      favorable outcome with acceptable morbidity.

PMID- 28761534
TI  - Efficacy of superficial temporal artery-middle cerebral artery bypass in
      cerebrovascular steno-occlusive diseases: Hemodynamics assessed by perfusion
      computed tomography.
AB  - OBJECTIVES: Our purpose of this study was to assess the cerebral hemodynamic
      improvement with perfusion computed tomography (CT), before and after superficial
      temporal artery (STA) to middle cerebral artery (MCA) bypass surgery in patients
      with cerebrovascular steno-occlusive diseases including both moyamoya disease and
      nonmoyamoya steno-occlusions. MATERIALS AND METHODS: Twenty-four STA-MCA bypasses
      were performed to 22 patients with symptomatic cerebrovascular steno-occlusive
      diseases, including both moyamoya disease and nonmoyamoya steno-occlusive
      diseases. Brain perfusion CT images were obtained before and after the bypass
      surgery. The relative parameters such as cerebral blood volume (CBV), cerebral
      blood flow (CBF), and mean transit time (MTT) derived from the perfusion CT were
      collected and analyzed to assess the efficacy of STA-MCA bypass. RESULTS: The CBF
      increased, and MTT decreased after the bypass surgery in both moyamoya group and
      nonmoyamoya group. The increase of CBF in nonmoyamoya group and the decrease of
      MTT delay in moyamoya group, overall group were statistically significant (P <
      0.05). No significant postoperative change in CBV was noted. During the
      postoperative follow-up period, none of the 22 patients experienced any repeated
      ischemic/hemorrhagic attacks nor any newly developed neurologic deficits.
      CONCLUSION: The STA-MCA bypass is an effective surgical management for patients
      with cerebrovascular steno-occlusive diseases, such as moyamoya disease and
      internal carotid artery/MCA steno-occlusion. And perfusion CT can be used as an
      effective quantitative modality to assess the cerebral perfusion before and after
      the STA-MCA bypass surgery.

PMID- 28761535
TI  - Prognostication in cervical spondylotic myelopathy: Proposal for a new simple
      practical scoring system.
AB  - CONTEXT: The ability to preoperatively predict the outcome in cervical
      spondylotic myelopathy (CSM) helps in planning management and counseling the
      patient and family. AIMS: A simple prognostic scale, namely, the Madras Institute
      of Neurology Prognostic Scale (MINPS) for CSM has been proposed. SETTINGS AND
      DESIGN: Six well-known prognostic factors, namely, age, duration of symptoms,
      neurological disability (Nurick's grade), number of levels of compression,
      effective canal diameter, and intrinsic cord changes, have been taken into
      account. Each factor has been divided into three subgroups and allotted a score.
      The total score in this scale ranges from a maximum of 18 to a minimum of 6.
      MATERIALS AND METHODS: This scale has been evaluated in a group of 85 patients
      operated for CSM. STATISTICAL ANALYSIS USED: The usefulness of MINPS was
      statistically assessed using ANOVA test. RESULTS: It has been found that majority
      of patients with a score of 14 or more improved; those with a score of 9 or less
      deteriorated; those with a score between 10 and 13 remained static. CONCLUSIONS:
      The MINPS for CSM is a very practical scale which can be applied easily with the
      available clinical and radiological data, with good accuracy of outcome
      prediction. This is the first scale of its kind.

PMID- 28761536
TI  - Brain metastases in cancer patients attending a Gamma Knife Center: A study from
      a single institute in Iran.
AB  - BACKGROUND: This study was aimed to explore data on brain metastases in cancer
      patients attending the Iranian Gamma Knife Center. METERIALS AND METHODS: This
      was a retrospective study. In all 5216 case records of patients who referred to
      the Iranian Gamma Knife Center for treatment of brain tumors during year 2003
      2011 were reviewed. Data were explored to identify patients who developed brain
      metastases due to cancer and assessed the information as applied to cancer
      patients including survival analysis. RESULTS: Two hundred and twenty patients
      were identified as having brain metastases due to cancer. The mean age of
      patients was 54.0 (standard deviation [SD] =12.7) years. Patients were followed
      for an average of 7 months after treatment with gamma-knife. The median survival
      time for different the Graded Prognostic Assessment (GPA) was: GPA: 0-1, 4.0 +/-
      0.4 months; GPA: 1.5-2.5, 6.0 +/- 0.7 months; GPA: 3, 9.0 +/- 0.9 months; and
      GPA: 3.5-4.0, 12.0 +/- 1.8 months and the overall median survival was 7.0 (SD =
      0.6) months. CONCLUSION: The findings suggest that many cancer patients in Iran
      might develop brain metastasis. Although, this is not a very high incidence
      compared with the existing statistics from other countries, there is an urgent
      need to explore the issue further.

PMID- 28761537
TI  - Endoscopic carpal tunnel decompression: Comparison of mid- and long-term outcomes
      of 30 endoscopic and 30 standard procedure carpal tunnel decompression
      operations.
AB  - BACKGROUND: Carpal tunnel syndrome is the most frequently seen trap neuropathy
      leads to pain, paresis, and weakness of hands. METHODS: Totally, 60 patients who
      underwent endoscopic or standard CTS surgery in Ibni Sina Hospital, Medical
      Faculty of Ankara university in the period of 2009 and 2012 were enrolled in this
      prospective study. RESULTS: During 36 months, 60 patients had undergone hand
      surgery. Totally, 14 male and 46 female patients of this serial had an average
      age of 51.24 (22-74) years. A number of 26 patients (43%) had left and 34 had
      (57%) right hand surgery. Complete relief of nocturnal paresis and pain has been
      shown in the 6th, 12th, and 24th month analyses of endoscopic surgery group
      results. Two patients in open surgery group underwent second operation due to
      relapse. The patients in the endoscopic group reported higher satisfaction
      cosmetically. CONCLUSION: Endoscopic carpal tunnel syndrome treatment is
      alternative and considerable option against standard open methods and due to low
      morbidity rates its performance is highly prevalent in recent years.

PMID- 28761539
TI  - Extensive intracranial calcification of pseudo-TORCH syndrome with features of
      Dandy-Walker malformation.
AB  - Pseudo-TORCH syndrome or congenital infection-like syndrome is a group of
      conditions which resemble congenital infections such as those caused by
      toxoplasmosis, rubella, cytomegalovirus (CMV), herpes (TORCH) group of organisms,
      clinico-radiologically, but serological tests are negative for the organisms. One
      of the variety shows features such as microcephaly, extensive intracranial
      calcification showing gross resemblance to congenital CMV infection, making its
      other name as microcephaly intracranial calcification syndrome (MICS). Dandy
      Walker malformation (DWM), in addition to posterior fossa large cyst, cerebellar
      vermis hypoplasia, and hydrocephalus is often associated with agenesis of the
      corpus callosum and callosal lipomas, dysplasia of the brainstem, and cerebellar
      hypoplasia or dysgenesis. But radiological features of DWM with microcephaly and
      intracranial calcification are very unusual and have been rarely reported in the
      literature.[1] We report a case of infant showing clinical features suggestive of
      congenital CMV infection with negative serology and radiological imaging
      suggestive of DWM with extensive intracranial calcification. Pseudo-TORCH
      syndrome with radiological features of DWM is a congenital developmental
      abnormality. Inspite of hydrocephalus, it does not require cerebrospinal fluid
      (CSF) diversionary procedure due to lack of increased intracranial pressure.
      Conservative management for seizure disorder is the optimal therapy.

PMID- 28761538
TI  - Recurrent intracranial Rosai-Dorfman disease: Management of a challenging case.
AB  - Rosai-Dorfman disease (RDD) is a rare, idiopathic, benign histioproliferative
      disorder. Extranodal involvement is seen in around 25-40% of patients. Central
      nervous system manifestation of RDD is uncommon and suprasellar location of the
      lesion is a distinct rarity. Surgery is the cornerstone of management of
      intracranial RDD. However, tumor recurrence or regrowth is a potential problem.
      Hence, low dose conformal radiotherapy (RT) should be considered in patients
      undergoing sub-total resection or having unresectable recurrent disease. Though
      cranial RT usually leads to satisfactory improvement of symptoms and long-term
      disease stabilization or regression, in few patients there may be an eventual
      progression of disease for which systemic chemotherapy may be considered. We have
      highlighted the salient features of this enigmatic disease by citing a case of a
      50-year-old male patient with suprasellar RDD treated by maximal safe surgery and
      deferred radiation therapy on progression.

PMID- 28761540
TI  - Neurosarcoidosis presenting as an incidental solitary cranial ring-enhancing
      lesion.
AB  - Isolated neurosarcoidosis without prior systemic symptoms is extremely rare,
      occurring in approximately 2% of patients with neurosarcoidosis. Due to its
      rarity, mistakes in diagnosis and treatment occur commonly. We present a case of
      a 47-year-old female who was found to have an incidentally discovered solitary
      intracranial lesion that mimicked a high-grade neoplasm, but was later confirmed
      to be neurosarcoidosis. Incidental solitary neurosarcoid granulomas are difficult
      to diagnose due to its nonspecific clinical and imaging presentations. Early
      diagnosis by biopsy in these rare incidental cases remains paramount for adequate
      treatment.

PMID- 28761541
TI  - Post-traumatic fibrous dysplasia of the parietal bone: A rare entity.
AB  - Fibrous dysplasia (FD) is a rare fibro-osseous lesion in which normal bone is
      replaced by abnormal fibrous tissue. Although a congenital disorder, a single
      case report of traumatic etiology had been described in the literature. We report
      a case of monostotic FD of the parietal calvarium in a 21-year-old female patient
      who presented to us with a single swelling in the parietal region been noticed
      after head injury sustained at the age of 7 years. After imaging investigations,
      the lesion was excised via craniotomy followed by cranioplasty in the same
      sitting. The histopathological evidence was suggestive of FD. To the best of our
      knowledge, this is the second case of a posttraumatic cranial FD and the first
      case describing the growing mass in the parietal bone secondary to head injury.

PMID- 28761542
TI  - Recurrent intraventricular meningioma with malignant transformation.
AB  - Benign meningioma undergoing a malignant transformation (to a chondrosarcoma) in
      intraventricular location is very rare and this is first case report to best of
      our knowledge. Herein, we report a rare case of malignant transformation of a
      benign intraventricular meningioma with relevant literature.

PMID- 28761543
TI  - Spinal capillary hemangiomas: Two cases reports and review of the literature.
AB  - Hemangiomas have rarely been found in the spinal cord. A few cases of spinal
      capillary hemangioma have been reported since 1987. The authors reported the two
      cases of capillary hemangioma including the tumor at conus medullaris and the
      another mimicked von Hippel-Lindau disease. A 15-year-old man was presented with
      coccydynia and left leg pain. A magnetic resonance imaging (MRI) revealed an
      intradural extramedullary enhancing mass at conus medullaris. Another case, a 31
      year-old man was presented with a history of familial history of brain tumor,
      retinal hemangioma both eyes, multiple pancreatic cyst and syringobulbia with
      syringohydromyelia. On MRI, a well-circumscribed intramedullary nodule was
      detected at C5-6 level and multiple subpial nodule along cervicothoracic spinal
      cord. All patients underwent surgery, and the histological diagnosis confirmed
      capillary hemangioma. Although rare and indistinguishable from other tumors,
      capillary hemangioma should be in the differential diagnosis of the spinal cord
      tumor.

PMID- 28761544
TI  - Removal of a low clival chordoma in a teenager by dorsolateral suboccipital
      transcondylar approach.
AB  - Chordomas are rare midline tumors of the central nervous system which arise from
      the remnants of the primitive notochord and have unique diagnostic and management
      challenges. Although recommended treatment for chordoma is radical resection,
      this may require extended skull base approaches. We report a case of low clival
      chordoma in a teenage patient which was successfully treated by dorsolateral
      suboccipital transcondylar approach.

PMID- 28761545
TI  - Primary pleomorphic xanthoastrocytoma of the spinal cord: A case report and
      review of literature.
AB  - Primary pleomorphic xanthoastrocytoma (PXA) of the spinal cord is a rare slow
      growing tumor. To our knowledge, only five such cases have been reported in the
      literature till date. We report the clinical, radiological, and histopathological
      features of a spinal PXA in a 23-year-old female previously operated 5 years back
      for a spinal tumor, presented with weakness in lower limbs, sphincter
      incontinence and low back pain. Magnetic resonance imaging scan with contrast
      reveals an intramedullary lesion in the spinal cord from D8-D10 level. The
      patient was operated with reexploration of the previous incision, and gross total
      excision was achieved. Histopathology confirmed the diagnosis of PXA. Clinical
      and radiological follow-up is required to detect early recurrence. Adjunct
      radiotherapy or and chemotherapy should be considered only when there is
      postoperative residual or recurrence, however there are no definite guidelines in
      view of the rarity of this condition.

PMID- 28761546
TI  - Spontaneous resolution of ruptured dissecting anterior inferior cerebellar artery
      aneurysm: A rare case report.
AB  - Dissecting anterior inferior cerebellar artery (AICA) aneurysms are extremely
      rare, and only nine cases are reported till date. We are reporting a case of
      ruptured dissecting distal AICA aneurysm with spontaneous resolution; first of
      its kind in the indexed literature.

PMID- 28761547
TI  - Plasmacytoma of the clivus.
AB  - We report a case of solitary plasmacytoma of the clivus in a 55 year old male.

PMID- 28761548
TI  - Intracranial en-plaque tuberculoma impersonating en-plaque meningioma: Case
      report and brief review of literature.
AB  - BACKGROUND: Tuberculosis of the central nervous system continues to be a major
      health hazard in developing countries like India. There are various
      manifestations of central nervous system tuberculosis including meningitis and
      space occupying lesions. We present a case of tuberculoma en-plaque which is
      often initially confused with a meningioma on presentation. We also review the
      literature relevant to this unusual entity. METHODS: A search of PubMed, PubMed
      Central, the Cochrane Library, and MEDLINE were performed to identify all English
      language reports of intracranial en-plaque tuberculomas. The combinations of text
      strings "tuberculoma," "en*," and "plaque" were used to perform the query on
      PubMed. Only the studies reporting intracranial en-plaque tuberculomas were
      included. RESULTS: Literature review revealed six reports on en-plaque
      tuberculomas including seven patients. The mean age at presentation was 40.5
      years, and no sex predilection was seen. Five of the six reported studies used
      anti-tuberculous therapy with or without surgical excision of the mass. Most of
      the patients in reported cases recovered fully. CONCLUSION: It is imperative to
      consider tuberculoma as an important differential when encountering intracranial
      en-plaque masses as en-plaque tuberculomas can be effectively treated with a
      combination of anti-tuberculosis therapy and surgical resection, yet consequences
      of a missed or late diagnosis can prove fatal.

PMID- 28761549
TI  - Intraventricular hemorrhage: A catastrophic complication after removal of old
      ventriculoperitoneal shunt.

PMID- 28761550
TI  - Posterior cranial fossa depressed fracture.

PMID- 28761551
TI  - Conventional axillary rolls in prolonged neurosurgical procedures: Time for
      reconsideration.

PMID- 28761552
TI  - Involvement of the visual change detection process in facilitating perceptual
      alternation in the bistable image.
AB  - A bistable image induces one of two perceptual alternatives. When the bistable
      visual image is continuously viewed, the percept of the image alternates from one
      possible percept to the other. Perceptual alternation was previously reported to
      be induced by an exogenous perturbation in the bistable image, and this
      perturbation was theoretically interpreted to cause neural noise, prompting a
      transition between two stable perceptual states. However, little is known
      experimentally about the visual processing of exogenously driven perceptual
      alternation. Based on the findings of a previous behavioral study (Urakawa et al.
      in Perception 45:474-482, 2016), the present study hypothesized that the
      automatic visual change detection process, which is relevant to the detection of
      a visual change in a sequence of visual events, has an enhancing effect on the
      induction of perceptual alternation, similar to neural noise. In order to clarify
      this issue, we developed a novel experimental paradigm in which visual mismatch
      negativity (vMMN), an electroencephalographic brain response that reflects visual
      change detection, was evoked while participants continuously viewed the bistable
      image. In terms of inter-individual differences in neural and behavioral data, we
      found that enhancements in the peak amplitude of vMMN1, early vMMN at a latency
      of approximately 150 ms, correlated with increases in the proportion of
      perceptual alternation across participants. Our results indicate the involvement
      of automatic visual change detection in the induction of perceptual alternation,
      similar to neural noise, thereby providing a deeper insight into the neural
      mechanisms underlying exogenously driven perceptual alternation in the bistable
      image.

PMID- 28761553
TI  - Scale-freeness of dominant and piecemeal perceptions during binocular rivalry.
AB  - When two eyes are simultaneously stimulated by two inconsistent images, the
      observer's perception switches between the two images every few seconds such that
      only one image is perceived at a time. This phenomenon is named binocular rivalry
      (BR). However, sometimes the perceived image is a piecemeal mixed of two stimuli
      known as piecemeal perceptions. In this study, a BR task was designed in which
      orthogonal gratings are presented to the two eyes. The subjects were trained to
      report 3 states: dominant perceptions (two state matching to perceived grating
      orientation) and the piecemeal perceptions (third state). We explored the scale
      freeness of the BR percept durations considering the two dominant monocular
      states as well as the piecemeal transition state using detrended fluctuation
      analysis. Our results reproduced the previous finding of memory in the perceptual
      switches between the monocular perception states. Moreover, we showed that such
      memory also exists in the transitory periods of dichoptic piecemeal perceptions.
      These results support our hypothesis that the pool of unstable piecemeal
      perceptions could be regarded as separate multiple low-depth basin in the
      perceptual state landscape. Likewise, the transitions from these piecemeal state
      basins and stable monocular state basins are faced with resistance. Therefore
      there is inertia and memory (i.e. positive serial correlation) for the piecemeal
      dichoptic perception states as well as the monocular states.

PMID- 28761554
TI  - Towards neuro-inspired symbolic models of cognition: linking neural dynamics to
      behaviors through asynchronous communications.
AB  - A computational architecture modeling the relation between perception and action
      is proposed. Basic brain processes representing synaptic plasticity are first
      abstracted through asynchronous communication protocols and implemented as
      virtual microcircuits. These are used in turn to build mesoscale circuits
      embodying parallel cognitive processes. Encoding these circuits into symbolic
      expressions gives finally rise to neuro-inspired programs that are compiled into
      pseudo-code to be interpreted by a virtual machine. Quantitative evaluation
      measures are given by the modification of synapse weights over time. This
      approach is illustrated by models of simple forms of behaviors exhibiting
      cognition up to the third level of animal awareness. As a potential benefit,
      symbolic models of emergent psychological mechanisms could lead to the discovery
      of the learning processes involved in the development of cognition. The
      executable specifications of an experimental platform allowing for the
      reproduction of simulated experiments are given in "Appendix".

PMID- 28761556
TI  - Synchronization of generalized reaction-diffusion neural networks with time
      varying delays based on general integral inequalities and sampled-data control
      approach.
AB  - This paper explores the problem of synchronization of a class of generalized
      reaction-diffusion neural networks with mixed time-varying delays. The mixed time
      varying delays under consideration comprise of both discrete and distributed
      delays. Due to the development and merits of digital controllers, sampled-data
      control is a natural choice to establish synchronization in continuous-time
      systems. Using a newly introduced integral inequality, less conservative
      synchronization criteria that assure the global asymptotic synchronization of the
      considered generalized reaction-diffusion neural network and mixed delays are
      established in terms of linear matrix inequalities (LMIs). The obtained easy-to
      test LMI-based synchronization criteria depends on the delay bounds in addition
      to the reaction-diffusion terms, which is more practicable. Upon solving these
      LMIs by using Matlab LMI control toolbox, a desired sampled-data controller gain
      can be acuqired without any difficulty. Finally, numerical examples are exploited
      to express the validity of the derived LMI-based synchronization criteria.

PMID- 28761555
TI  - Affective pictures processing is reflected by an increased long-distance EEG
      connectivity.
AB  - Analysis of affective picture processing by means of EEG has invaded the
      literature. The methodology of event-related EEG coherence is one of the
      essential methods used to analyze functional connectivity. The aims of the
      present study are to find out the long range EEG connectivity changes in
      perception of different affective pictures and analyze gender differences in
      these long range connected networks. EEGs of 28 healthy subjects (14 female) were
      recorded at 32 locations. The participants passively viewed emotional pictures
      (IAPS, unpleasant, pleasant, neutral). The long-distance intra-hemispheric event
      related coherence was analyzed for delta (1-3.5 Hz), theta (4-7.5 Hz), and alpha
      (8-13 Hz) frequency ranges for F3-T7, F4-T8, F3-TP7, F4-TP8, F3-P3, F4-P4, F3-O1,
      F4-O2, C3-O1, C4-O2 electrode pairs. Unpleasant pictures elicited significantly
      higher delta coherence values than neutral pictures (p < 0.05), over fronto
      parietal, fronto-occipital, and centro-occipital electrode pairs. Furthermore,
      unpleasant pictures elicited higher theta coherence values than pleasant (p <
      0.05) and neutral pictures (p < 0.05). The present study showed that female
      subjects had higher delta (p < 0.05) and theta (p < 0.05) coherence values than
      male subjects. This difference was observed more for emotional pictures than for
      neutral pictures. This study showed that the brain connectivity was higher during
      emotional pictures than neutral pictures. Females had higher connectivity between
      different parts of the brain than males during emotional processes. According to
      these results, we may comment that increased valence and arousal caused increased
      brain activity. It seems that not just single sources but functional networks
      were also activated during perception of emotional pictures.

PMID- 28761557
TI  - Cooperative effect of random and time-periodic coupling strength on
      synchronization transitions in one-way coupled neural system: mean field
      approach.
AB  - The cooperative effect of random coupling strength and time-periodic coupling
      strengh on synchronization transitions in one-way coupled neural system has been
      investigated by mean field approach. Results show that cooperative coupling
      strength (CCS) plays an active role for the enhancement of synchronization
      transitions. There exist an optimal frequency of CCS which makes the system
      display the best CCS-induced synchronization transitions, a critical frequency of
      CCS which can not further affect the CCS-induced synchronization transitions, and
      a critical amplitude of CCS which can not occur the CCS-induced synchronization
      transitions. Meanwhile, noise intensity plays a negative role for the CCS-induced
      synchronization transitions. Furthermore, it is found that the novel CCS
      amplitude-induced synchronization transitions and CCS frequency-induced
      synchronization transitions are found.

PMID- 28761558
TI  - The human brain from above: an increase in complexity from environmental stimuli
      to abstractions.
AB  - Contrary to common belief, the brain appears to increase the complexity from the
      perceived object to the idea of it. Topological models predict indeed that: (a)
      increases in anatomical/functional dimensions and symmetries occur in the
      transition from the environment to the higher activities of the brain, and (b)
      informational entropy in the primary sensory areas is lower than in the higher
      associative ones. To demonstrate this novel hypothesis, we introduce a
      straightforward approach to measuring island information levels in fMRI
      neuroimages, via Renyi entropy derived from tessellated fMRI images. This
      approach facilitates objective detection of entropy and corresponding information
      levels in zones of fMRI images generally not taken into account. We found that
      the Renyi entropy is higher in associative cortices than in the visual primary
      ones. This suggests that the brain lies in dimensions higher than the environment
      and that it does not concentrate, but rather dilutes messages coming from
      external inputs.

PMID- 28761559
TI  - Toxicity and Apoptosis Related Effects of Benzimidazo [3,2-alpha] Quinolinium
      Salts Upon Human Lymphoma Cells.
AB  - OBJECTIVES: The present study evaluates novel cationic quinoline derivatives
      known as benzimidazo[3,2-a]quinolinium salts (BQS) named NBQ-48 and ABQ-48 that
      have structural similarities to known anti-cancer substances such as ellipticine
      and berberine. METHODS: Toledo human lymphoma (ATCC CRL2631) cells were treated
      for 24 to 48 hours. Apoptosis related endpoints such as cell cycle arrest,
      mitochondrial damage, RNS and ROS generation and the activity of several
      apoptosis related proteins such as caspases and apoptosis inducing factor (AIF)
      were studied using fluorescence staining and western blot respectively. RESULTS:
      Results indicated a higher toxicity from the amino substituted ABQ-48 versus the
      NBQ-48 (GI50's of 50uM versus 100uM respectively). Both compounds induced cell
      death through various apoptosis related endpoints including a decrease in
      mitochondrial membrane potential with an increase in ROS and activation of the
      effector caspase 3. Interestingly, AIF release was observed on cells treated with
      the amino substituted ABQ-48 but not on the nitro substituted NBQ-48 samples
      suggesting a caspase independent mechanism for ABQ-48. CONCLUSIONS: The results
      obtained presents the toxic effects of two novel benzimidazo[3,2-a]quinolinium
      salts in human lymphoma tumor cells. The identified mechanism of action includes
      multiple apoptosis related effects. Furthermore the data presents a clear
      variation in caspase dependent or independent mechanism for each compound.

PMID- 28761560
TI  - Design and Analysis of a Continuous Split Typed Needle-Free Injection System for
      Animal Vaccination.
AB  - BACKGROUND: Liquid needle-free injection devices (NFIDs) employ a high-velocity
      liquid jet to deliver drugs and vaccine through transdermal injection. NFIDs for
      animal vaccination are more complicated than those used for human beings for
      their much larger and more flexible power sources, as well as rapid, repetitive
      and continuous injection features. METHOD: In the paper, spring-powered NFID is
      designed for animal vaccine injection. For convenience, the device is a split
      into a power source and handheld injector. A mathematical model is proposed to
      calculate the injection pressure, taking into the account pressure loss and the
      strain energy loss in the bendable tube due to elastic deformation. An
      experimental apparatus was build to verify the calculation results. RESULTS AND
      CONCLUSION: Under the same system conditions, the calculation results of the
      dynamic injection pressure match the experimental results. It is found that the
      bendable tube of the split typed NFID has significant impact on the profile of
      the injection pressure. The initial peak pressure is less than the initial peak
      pressure of NFID without bendable tube, and there is occurrence time lag of the
      peak pressure. The mathematical model is the first attempt to reveal the
      relationship between the injection pressure and the system variables of split
      typed NFID.

PMID- 28761561
TI  - Coronary Perforation of Distal Diagonal Branch Followed by Prolonged Recurrent
      Cardiac Tamponade Finally Resolved with Pericardiotomy - the Potential Risk of
      Hydrophilic Guide-Wires.
AB  - PURPOSE: Coronary artery perforation (CAP) is a complication of percutaneous
      coronary interventions (PCIs). Hydrophilic guide-wires have been shown to
      increase the probability of CAP. Depending on the size of perforations we adopt
      different treatments. CASE: We present the case of a 73-year old male with
      coronary artery disease and severe aortic valve stenosis. The patient was in the
      process of qualifying for a transcatheter aortic valve implantation.
      Unfortunately, CAP of the first diagonal branch of the LAD occurred during PCI.
      Initially, abrupt bleeding to the pericardial sac was primarily restrained.
      However, in the following days, pericardial bleeding became silent, prolonged and
      finally resulted in surgical pericardiotomy and surgical aortic valve
      replacement. CONCLUSION: This case depicts that in some cases, more aggressive
      endovascular treatment of CAP during the acute phase could decrease the
      probability of future radical surgical treatment. Although, in other cases,
      avoiding radical endovascular treatment of CAP and secondary necrosis along the
      distribution of the artery culminates in a higher risk for conversion to a
      surgical cardiac procedure. Accurate primary assessment of CAP seriousness and
      careful observation after PCI could improve results and lead to avoiding severe
      complications.

PMID- 28761562
TI  - Assessment of Physicochemical and Microbiological Quality of Public Swimming
      Pools in Addis Ababa, Ethiopia.
AB  - BACKGROUND: From swimming pools, bathers may acquire many potential pathogens or
      may be affected by the physicochemical characteristics of water used during
      bathing. Hence, this study aimed at assessing the physicochemical and
      microbiological quality of public swimming pools located at different hotels and
      recreation center in Addis Ababa, Ethiopia. METHOD: A cross sectional study was
      carried out from February to May, 2016. Nine hotels and one recreation center
      which recognized to have public swimming services were included. A total of 60
      swimming pool water samples from 10 swimming pools were collected at deeper,
      shallow and intake point twice on a weekly basis using a 250 ml sterile bottle
      containing sodium thiosulphate. PH, residual chlorine and temperature of samples
      were recorded at the time of collection. Sample containing bottles were
      transported in ice box to microbiological laboratory and analyzed on the same
      day. Standard cultural and biochemical methods were used for isolation and
      characterization of the main microbial groups. Total viable count, total coliform
      count, fecal coliform count and E. coli were determined. Data was analyzed using
      SPSS Version 20. RESULTS: Average PH and temperature of swimming pool water
      samples were 7.1 and 29oC respectively. Of all analyzed water samples, 58.4%
      (n=35/60) of them had PH range of 7.2-7.8, 58.3% (n=35/60) of samples had
      temperature in the range of 21oC-32oC and 25% (n=15/60) of water samples had
      residual chlorine in the range of 2-3mg/l. 73.3% (n=44/60) of the samples had a
      total viable count below 200 MPN/ml and 70% (n-42/60) of the samples had Total
      Coliform Count values less than 2 MPN/100 ml. Moreover, 66.7% (n=40/60) of the
      samples had fecal coliform counts falling below 1 MPN /100 ml. E. coli was absent
      in 70% (n=42/60) of the samples while it was present in 30% (n=18/60) of the
      samples. CONCLUSION: PH, residual chlorine and temperature value of majority of
      the swimming pools' water samples were within the acceptable limit. Regarding
      microbial quality, most swimming pools' water samples complied to the WHO
      standard. Swimming pools that did not comply to the standard both in
      physicochemical levels and microbial quality need improvement due to their
      significant health implication.

PMID- 28761563
TI  - The Emerging Role of The Eosinophil and Its Measurement in Chronic Cough.
AB  - Although the aetiology of chronic cough in guidelines is clearly stated as asthma
      and related syndromes, gastro-oesophageal reflux disease (GORD), and upper
      airways disease, the inflammatory mechanisms underlying these conditions differ.
      Recent studies on asthma have increasingly focused on its molecular phenotypes
      instead of clinical characteristics. Here, we proposed the hypothesis that
      divides cough into two groups; the eosinophilic and neutrophilic. This division
      will enhance our ability to recognise the type of airway inflammation which, as a
      consequence will lead us to more targeted and personalized treatment approaches.

PMID- 28761564
TI  - Predictive Value of Serum Infliximab Levels at Induction Phase in Rheumatoid
      Arthritis Patients.
AB  - BACKGROUND: The Infliximab, has proven effective in treating rheumatoid arthritis
      (RA). A good clinical response is usually associated with high serum drug levels.
      Development of antibodies toward Infliximab (ATI) can increase drug clearance,
      leading to treatment failure. AIMS: To analyze whether serum Infliximab trough
      levels (ITL) at the induction phase are associated with Infliximab clearance and
      clinical outcomes at week(W) 54 and to investigate the association with
      immunogenicity development. METHODS: Observational retrospective study in which
      ITL from 66 RA patients were measured by capture ELISA at W0, W2, W6, W14 and 22.
      Patients were classified as ITLpos if Infliximab was detectable at W54 and ITLneg
      otherwise. ATI were assayed by bridging ELISA and by two drug-tolerant assays.
      ITL cut-off values were established by ROC curves. The association between ITL at
      early-stage and clearance of Infliximab at W54 was analyzed by univariable and
      multivariable logistic regression. RESULTS: ITLneg patients (n=25) always had
      significantly lower Infliximab levels than ITLpos (n=41). An ITL value of 4.4
      MUg/mL at W6 best predicted W54 Infliximab absence. In the multivariable
      analysis, only ITL below the cut-off at W6 (OR: 86.6; 95%CI: 6.58-1139.99) and
      non-use of methotrexate (OR: 6.9; 95%CI: 1.04-45.84) remained significantly
      associated with W54 Infliximab absence. ATI were more frequent in patients with
      ITL below the cut-off at W6. CONCLUSIONS: In RA, ITL at induction phase are
      inversely associated with Infliximab clearance and clinical outcomes at W54. ATI
      was the main reason for low early ITL. A predictive value of ITL at W6 was found
      as a useful prognostic measure of treatment efficacy.

PMID- 28761565
TI  - First Reported Case of Donor Related Candida Endophthalmitis after Descemet
      Membrane Endothelial Keratoplasty.
AB  - PURPOSE: To report the first case of Candida donor to host transmission following
      descemet membrane endothelial keratoplasty (DMEK). METHODS: A retrospective case
      report. RESULTS: A patient underwent uneventful DMEK. Following surgery the donor
      rim was culture positive for Candida. The patient developed fungal
      endophthalmitis that was treated medically with multiple injections of
      voriconazole and amphotericin. Medical treatment was unable to clear the
      infection and removal of the donor material was required. Following removal the
      infection subsided. CONCLUSION: Candida interface keratitis and endophthalmitis
      can occur following DMEK and may be difficult to treat medically. Early removal
      of the donor material should be considered.

PMID- 28761567
TI  - Using an Image Fusion Methodology to Improve Efficiency and Traceability of
      Posterior Pole Vessel Analysis by ROPtool.
AB  - BACKGROUND: The diagnosis of plus disease in retinopathy of prematurity (ROP)
      largely determines the need for treatment; however, this diagnosis is subjective.
      To make the diagnosis of plus disease more objective, semi-automated computer
      programs (e.g. ROPtool) have been created to quantify vascular dilation and
      tortuosity. ROPtool can accurately analyze blood vessels only in images with very
      good quality, but many still images captured by indirect ophthalmoscopy have
      insufficient image quality for ROPtool analysis. PURPOSE: To evaluate the ability
      of an image fusion methodology (robust mosaicing) to increase the efficiency and
      traceability of posterior pole vessel analysis by ROPtool. MATERIALS AND
      METHODOLOGY: We retrospectively reviewed video indirect ophthalmoscopy images
      acquired during routine ROP examinations and selected the best unenhanced still
      image from the video for each infant. Robust mosaicing was used to create an
      enhanced mosaic image from the same video for each eye. We evaluated the time
      required for ROPtool analysis as well as ROPtool's ability to analyze vessels in
      enhanced vs. unenhanced images. RESULTS: We included 39 eyes of 39 infants.
      ROPtool analysis was faster (125 vs. 152 seconds; p=0.02) in enhanced vs.
      unenhanced images, respectively. ROPtool was able to trace retinal vessels in
      more quadrants (143/156, 92% vs 115/156, 74%; p=0.16) in enhanced mosaic vs.
      unenhanced still images, respectively and in more overall (38/39, 97% vs. 34/39,
      87%; p=0.07) enhanced mosaic vs. unenhanced still images, respectively.
      CONCLUSION: Retinal image enhancement using robust mosaicing advances efforts to
      automate grading of posterior pole disease in ROP.

PMID- 28761568
TI  - The Effects of Ramadan Fasting on Anterior Segment Parameters, Visual Acuity and
      Intraocular Pressures of the Eye.
AB  - OBJECTIVE: It is aimed to determine whether fasting during Ramadan has any
      significant effect on anterior chamber parameters, visual acuity and intraocular
      pressures. METHODS: 31 fasting (Group 1) and 30 non-fasting healthy volunteers
      (Group 2) were enrolled. All cases underwent an ophthalmological examination and
      anterior segment parameter evaluation (central corneal thickness (CCT), anterior
      chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA),
      pupil size) with Pentacam before and after the breaking of the Ramadan fast in
      Group 1, before and after dinner in Group 2. RESULTS: The mean age was 43.35 +/-
      13.20 in Group 1, 43.17 +/- 12.90 in Group 2 (p= 0.955). No significant
      difference was detected in any of the parameters in both groups. CONCLUSION:
      There is a need for more detailed and associated studies to understand better
      about the influence of Ramadan fast on various ocular parameters.

PMID- 28761569
TI  - Efficacy and Safety of Switching from Prostaglandin Analog Therapy to
      Prostaglandin / Timolol Fixed Combination or Prostaglandin / Brimonidine Therapy.
AB  - BACKGROUND: To compare the safety and efficacy between switching to
      prostaglandin/timolol fixed combination eye drops (PG/timolol FCs) and adding
      brimonidine to PG analogue monotherapy. METHODS: Eyes of 53 patients with primary
      open-angle glaucoma or ocular hypertension who were receiving PG analogue
      monotherapy were included. Participants were randomly divided into two treatment
      groups: one was prescribed PG/timolol FCs (switched group), and for the other,
      0.1% brimonidine was added to the PG analogue (added group). Intraocular pressure
      (IOP), blood pressure, and pulse rate were measured after 1 and 3 months and
      compared to baseline values. Participants were also surveyed to determine if they
      had experienced systemic or topical adverse events at each study visit. IOP
      changes at 1 and 3 months were compared between groups. RESULTS: Three months
      after changing medication, mean IOP was 14.6 +/- 2.4 mmHg in the switched group
      and 13.7 +/- 1.8 mmHg in the added group; both were significantly lower than the
      baseline values (switched group, 16.5 +/- 2.7 mmHg; added group, 15.8 +/- 2.3
      mmHg; both P < 0.001). Neither the mean nor the percentage reductions in IOP were
      significantly different between groups at 1 and 3 months. In the added group,
      diastolic blood pressure was lower than that at 1 and 3 months, systolic blood
      was lower than that at 3 months (P < 0.01). The patients who had experienced
      systemic or topical adverse events were 53.8% in the added group and 40.7% in the
      the changed group, which was equivalent between groups (P =0.4142). Three
      patients (11.5%) in the added group, but none from the switched group, were
      excluded from analyses because of adverse events (not significant, P = 0.217).
      CONCLUSION: Switching from a PG analogue to PG/timolol FCs or to PG with
      brimonidine was equally safe (systemically and topically) and effective in
      reducing IOP. Thus, PG with brimonidine might be appropriate medication in
      patients who cannot use PG/timolol FCs due to repiratory or circulatory disease.

PMID- 28761570
TI  - Estimation of the Basic Reproduction Number of Novel Influenza A (H1N1) pdm09 in
      Elementary Schools Using the SIR Model.
AB  - BACKGROUND: The novel influenza A (H1N1) pdm09 (A/H1N1pdm) pandemic of 2009-2010
      had a great impact on society. OBJECTIVE: We analyzed data from the absentee
      survey, conducted in elementary schools of Oita City, to evaluate the A/H1N1pdm
      pandemic and to estimate the basic reproductive number (R0 ) of this novel
      strain. METHOD: We summarized the overall absentee data and calculated the
      cumulative infection rate. Then, we classified the data into 3 groups according
      to school size: small (<300 students), medium (300-600 students), and large (>600
      students). Last, we estimated the R0 value by using the Susceptible-Infected
      Recovered (SIR) mathematical model. RESULTS: Data from 60 schools and 27,403
      students were analyzed. The overall cumulative infection rate was 44.4%. There
      were no significant differences among the grades, but the cumulative infection
      rate increased as the school size increased, being 37.7%, 44.4%, and 46.6% in the
      small, medium, and large school groups, respectively. The optimal R0 value was
      1.33, comparable with that previously reported. The data from the absentee survey
      were reliable, with no missing values. Hence, the R0 derived from the SIR model
      closely reflected the observed R0 . The findings support previous reports that
      school children are most susceptible to A/H1N1pdm virus infection and suggest
      that the scale of an outbreak is associated with the size of the school.
      CONCLUSION: Our results provide further information about the A/H1N1pdm pandemic.
      We propose that an absentee survey should be implemented in the early stages of
      an epidemic, to prevent a pandemic.

PMID- 28761566
TI  - Many Faces of Renin-angiotensin System - Focus on Eye.
AB  - The renin-angiotensin system (RAS), that is known for its role in the regulation
      of blood pressure as well as in fluid and electrolyte homeostasis, comprises
      dozens of angiotensin peptides and peptidases and at least six receptors. Six
      central components constitute the two main axes of the RAS cascade. Angiotensin
      (1-7), an angiotensin converting enzyme 2 and Mas receptor axis (ACE2-Ang(1-7)
      MasR) counterbalances the harmful effects of the angiotensin II, angiotensin
      converting enzyme 1 and angiotensin II type 1 receptor axis (ACE1-AngII-AT1R)
      Whereas systemic RAS is an important factor in blood pressure regulation, tissue
      specific regulatory system, responsible for long term regional changes, that has
      been found in various organs. In other words, RAS is not only endocrine but also
      complicated autocrine system. The human eye has its own intraocular RAS that is
      present e.g. in the structures involved in aqueous humor dynamics. Local RAS may
      thus be a target in the development of new anti-glaucomatous drugs. In this
      review, we first describe the systemic RAS cascade and then the local ocular RAS
      especially in the anterior part of the eye.

PMID- 28761572
TI  - A Case of Severe Iron Deficiency Anemia Associated with Long-Term Proton Pump
      Inhibitor Use.
AB  - The use of proton pump inhibitors (PPIs) in the treatment of gastrointestinal
      diseases has evolved over recent years. Initially intended for short-term use,
      PPIs are increasingly being used, often inappropriately, as long-term maintenance
      medications. The mechanism of action of PPIs is suppression of gastric basal and
      stimulated acid secretion by inhibiting the parietal cell H+/K+ ATP pump with a
      resultant increase in gastric pH and hypo- or achlorhydria. Although short-term
      use is related to few adverse effects, long-term use is associated with numerous
      complications. We present the case of a 58-year-old man with severe iron
      deficiency anemia due to malabsorption suspected to be caused by long-term PPI
      use. An extensive medical work up failed to reveal any definitive source of
      bleeding. An iron malabsorption test confirmed that iron was not being absorbed
      from the gastrointestinal tract. The Naranjo Adverse Drug Reaction Probability
      Scale and the Horn and Hansten Drug Interaction Probability Scale are suggestive
      of an association between long-term PPI use and the observed iron deficiency
      anemia. However, the patient's death and lack of an autopsy prevented
      confirmatory follow-up data from being obtained to connect long-term PPI use as
      the culprit. Although there are currently no recommendations regarding screening
      for iron deficiency and/or anemia in patients on long-term PPI therapy,
      physicians should be aware of this potential side effect and consider monitoring
      in high-risk patients.

PMID- 28761571
TI  - Extending Inferential Group Analysis in Type 2 Diabetic Patients with
      Multivariate GLM Implemented in SPM8.
AB  - BACKGROUND: Although voxel based morphometry studies are still the standard for
      analyzing brain structure, their dependence on massive univariate inferential
      methods is a limiting factor. A better understanding of brain pathologies can be
      achieved by applying inferential multivariate methods, which allow the study of
      multiple dependent variables, e.g. different imaging modalities of the same
      subject. OBJECTIVE: Given the widespread use of SPM software in the brain imaging
      community, the main aim of this work is the implementation of massive
      multivariate inferential analysis as a toolbox in this software package. applied
      to the use of T1 and T2 structural data from diabetic patients and controls. This
      implementation was compared with the traditional ANCOVA in SPM and a similar
      multivariate GLM toolbox (MRM). METHOD: We implemented the new toolbox and tested
      it by investigating brain alterations on a cohort of twenty-eight type 2 diabetes
      patients and twenty-six matched healthy controls, using information from both T1
      and T2 weighted structural MRI scans, both separately - using standard univariate
      VBM - and simultaneously, with multivariate analyses. RESULTS: Univariate VBM
      replicated predominantly bilateral changes in basal ganglia and insular regions
      in type 2 diabetes patients. On the other hand, multivariate analyses replicated
      key findings of univariate results, while also revealing the thalami as
      additional foci of pathology. CONCLUSION: While the presented algorithm must be
      further optimized, the proposed toolbox is the first implementation of
      multivariate statistics in SPM8 as a user-friendly toolbox, which shows great
      potential and is ready to be validated in other clinical cohorts and modalities.

PMID- 28761573
TI  - Safety, Efficacy, and Bioavailability of Fixed-Dose Combinations in Type 2
      Diabetes Mellitus: A Systematic Updated Review.
AB  - PURPOSE: Type 2 diabetes mellitus (T2DM) is a multifactorial disease
      characterized by insulin resistance. As time progresses, monotherapy often does
      not provide effective glycemic control, generating the need for an add-on
      therapy. Hence, multiple oral hypoglycemic agents formulated as a single-dose
      form called fixed-dose combinations (FDCs) play an essential role in glycemic
      control. The purpose of this systematic review is to appraise the recently
      published evidence on the safety, efficacy, and bioavailability of FDCs. METHODS:
      A comprehensive literature search of PUBMED, Scopus, ScienceDirect.com, ProQuest,
      SpringerLink, clintrials.gov, Embase, and EBSCO using the key words FDCs,
      combination therapy, T2DM management, and add-on therapy was conducted. Studies
      on the safety profile/tolerability, efficacy, and bioavailability of various FDCs
      of oral hypoglycemic agents were preferred. FINDINGS: The systematic review of
      all the publications suggests that FDCs of oral hypoglycemic agents (OHAs)
      significantly reduce HbA1c and fasting plasma glucose values, thereby efficiently
      reducing hyperglycemia in patients in whom monotherapy fails. FDCs are the
      bioequivalent of the concomitant drugs administered as individual components.
      Improved adherence to FDCs and the absence of serious adverse drug reactions
      compared with dual therapy play an important role in decreasing the incidence of
      hyperglycemia in patients with T2DM. IMPLICATIONS: From this updated review, it
      was found that metformin was the most widely used component of FDCs with other
      OHAs. Studies on the safety and efficacy of newly approved OHAs such as sodium
      glucose cotransporter inhibitors were limited. An increasing number of randomized
      trials on the safety and efficacy of newly emerging FDCs suggests that they would
      be better treatment options for T2DM patients.

PMID- 28761575
TI  - Chemical Stability of Ceftolozane/Tazobactam in Polyvinylchloride Bags and
      Elastomeric Pumps.
AB  - BACKGROUND: Elastomeric pumps are often used to administer intravenous
      antibiotics in the outpatient setting, but effective infusion requires that the
      drug remain stable in solution throughout the procedure. OBJECTIVE: To determine
      the chemical stability of ceftolozane/tazobactam when reconstituted and stored
      over an extended time in the AccuFlo (EMED Technologies, El Dorado Hills,
      California) and I-Flow Homepump Eclipse (Halyard, Alpharetta, Georgia)
      elastomeric pumps compared with the results of the label-supporting studies in
      polyvinylchloride (PVC) bags. METHODS: Two ceftolozane/tazobactam dosages were
      tested for the elastomeric pump studies: 1500 mg (1 g ceftolozane/0.5 g
      tazobactam) and 150 mg (100 mg ceftolozane/50 mg tazobactam). The solution hold
      time was evaluated for 10 days at 5 degrees C (+/-3 degrees C) (tolerance +/-3
      hours) and for 1 day (24 hours) at ambient room temperature (tolerance +/-3
      hours). Results of a previously conducted label-supporting PVC intravenous bag
      study were used as a comparator. RESULTS: At each time point, the visual
      appearance of all pump and PVC bag solutions remained clear and free of visible
      particulates, and subvisible particulate matter did not differ significantly
      between the initial time point and at 10 days. No notable changes in pH in any of
      the pump or PVC solutions occurred throughout the study. Recovery of ceftolozane
      and tazobactam was greater than 93% and 94%, respectively, for all samples
      (elastomeric pump and PVC bag) at 10 days. CONCLUSIONS: Ceftolozane/tazobactam
      remains physically and chemically stable for at least 7 days, as indicated on the
      US label, when reconstituted, diluted, and stored in the AccuFlo and I-Flow
      Homepump Eclipse elastomeric pumps and in PVC intravenous bags.

PMID- 28761576
TI  - Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin on
      Atherosclerosis, beta-Cell Function, and Glycemic Control in Japanese Patients
      with Type 2 Diabetes Mellitus Who are Treatment Naive or Poorly Responsive to
      Antidiabetes Agents: A Multicenter, Prospective Observational, Uncontrolled
      Study.
AB  - BACKGROUND: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is widely used in
      patients with type 2 diabetes. However, the pleiotropic effects of sitagliptin is
      not well understood. OBJECTIVE: To assess the clinical efficacy and safety of
      sitagliptin on atherosclerosis, beta-cell function, and glycemic control in
      Japanese patients with type 2 diabetes. METHODS: A prospective observational
      study of 270 patients with type 2 diabetes mellitus was carried out. Patients
      (aged 64.3 [12.4] years, body mas index 25.2 [4.3]) with glycated hemoglobin
      >6.9% (52 mmol/mol) or fasting plasma glucose >130 mg/dL were treated with
      sitagliptin for 12 months. The primary end point was glycated hemoglobin level
      changes from baseline to 3 months. The secondary end points included changes in
      several biomarkers related to inflammation and beta-cell function from baseline
      to 3 months, as well as changes in glycated hemoglobin level from baseline to 12
      months. RESULTS: Glycated hemoglobin levels were significantly lower in patients
      treated with sitagliptin for 3 months than at baseline (8.1% [1.4%]-7.3% [1.2%])
      (65 [16.9]-56 [13.1] mmol/mol]) (P < 0.0001), which continued after 12 months
      (7.4% [1.3%]) (56 [15.2] mmol/mol) (P < 0.0001). In addition, a marker of
      vascular-specific inflammation, pentraxin-3, and a marker of beta-cell function
      (proinsulin/insulin ratio), respectively, were lower after treatment with
      sitagliptin for 3 months than at baseline (1.88 [0.78]-1.65 [0.63] ng/mL [P =
      0.0038] and 0.20 [0.14]-0.17 [0.11] [P = 0.01], respectively). On the other hand,
      a biomarker reflecting whole body inflammation; that is, high-sensitivity C
      reactive protein level, was unchanged. Adverse events occurred in 14 patients
      (5.18%). CONCLUSIONS: Sitagliptin may have beneficial effects on vascular
      inflammation and beta-cell function in Japanese patients with type 2 diabetes.
      Pentraxin-3 may be an early predictive marker for detecting the
      antiatherosclerotic effects of dipeptidyl peptidase-4.

PMID- 28761574
TI  - Repurposed Therapeutic Agents Targeting the Ebola Virus: A Systematic Review.
AB  - BACKGROUND: The Ebola virus has been responsible for numerous outbreaks since the
      1970s, with the most recent outbreak taking place between 2014 and 2016 and
      causing an international public health emergency. Ebola virus disease (EVD) has a
      high mortality rate and no approved targeted treatment exists to date. A number
      of established drugs are being considered as potential therapeutic agents for the
      treatment of EVD. OBJECTIVE: We aimed to identify potential drug repositioning
      candidates and to assess the scientific evidence available on their efficacy.
      METHODS: We conducted a systematic literature search in MEDLINE, Embase, and
      other relevant trial registry platforms for studies published between January
      1976 and January 2017. We included drug screening, preclinical studies, and
      clinical studies on repurposed drugs for the treatment of EVD. The risk of bias
      for animal studies and nonrandomized clinical studies was assessed. The quality
      of reporting for case series and case reports was evaluated. Finally, we selected
      drugs approved by established regulatory authorities, which have positive in
      vitro study outcomes and at least one additional animal or clinical trial.
      RESULTS: We identified 3301 publications, of which 37 studies fulfilled our
      inclusion criteria. Studies were highly heterogeneous in terms of study type,
      methodology, and intervention. The risk of bias was high for 13 out of 14 animal
      studies. We selected 11 drugs with potential anti-EVD therapeutic effects and
      summarized their evidence. CONCLUSIONS: Several established drugs may have
      therapeutic effects on EVD, but the quality and quantity of current scientific
      evidence is lacking. This review highlights the need for well-designed and
      conducted preclinical and clinical research to establish the efficacy of
      potential repurposed drugs against EVD.

PMID- 28761577
TI  - Bleeding Risk Related to Upper Gastrointestinal Endoscopic Biopsy in Patients
      Receiving Antithrombotic Therapy: A Multicenter Prospective Observational Study.
AB  - BACKGROUND: Although antithrombotic agents are widely used for cardiac and
      cerebrovascular disease prevention, they increase the risk of gastrointestinal
      (GI) bleeding. OBJECTIVE: To examine GI bleeding risk in association with an
      esophagogastroduodenoscopy (EGD) biopsy performed in patients without cessation
      of antithrombotic therapy. METHODS: This study was prospectively conducted at 14
      centers. EGD biopsies were performed in patients receiving antithrombotic agents
      without cessation, as well as age- and sex-matched controls not receiving
      antithrombotic therapy. Patients treated with warfarin before the biopsy had a
      prothrombin time-international normalized ratio level <3.0. The proportion of GI
      bleeding events was compared between the groups. RESULTS: The patient group (n =
      277) underwent a total of 560 biopsies while continuing antithrombotic therapy,
      of whom 24 were receiving multiple antiplatelet drugs, and 9 were receiving both
      antiplatelet and anticoagulant agents. The control patients (n = 263) underwent
      557 biopsies. The upper-GI bleeding rate within 30 days after the EGD biopsy did
      not increase in patients without cessation of antithrombotic treatment,
      regardless of receiving single or multiple antithrombotic agents. CONCLUSIONS: We
      found no significant increase in upper-GI bleeding risk following an EGD biopsy
      in patients taking antithrombotic agents, suggesting its safety without the need
      for antithrombotic treatment interruption.

PMID- 28761578
TI  - Esophageal Motility and Rikkunshito Treatment for Proton Pump Inhibitor
      Refractory Nonerosive Reflux Disease: A Prospective, Uncontrolled, Open-Label
      Pilot Study Trial.
AB  - BACKGROUND: Only a few reports focused on esophageal motility in patients with
      proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) and there
      has been no established strategy for treatment. OBJECTIVE: To clarify the
      characteristics of esophageal motility in patients with PPI-refractory NERD, we
      evaluated esophageal function using combined multichannel intraluminal impedance
      and esophageal manometry (MII-EM). In addition, we evaluated the efficacy of
      rikkunshito (RKT), which is a gastrointestinal prokinetic agent. METHODS: Thirty
      patients with NERD were enrolled and underwent MII-EM. After 8 weeks of RKT (7.5
      g/d) treatment, MII-EM was repeated on patients with PPI-refractory NERD.
      Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. RESULTS: In
      patients with PPI-refractory NERD, measures of complete bolus transit,
      peristaltic contractions, and residual pressure of the lower esophageal sphincter
      during swallowing deviated from the standard values and esophageal clearance was
      found to be deteriorated. RKT significantly improved the peristaltic contractions
      (P < 0.05), the complete bolus transit (P < 0.01), and the residual pressure of
      lower esophageal sphincter (P < 0.05) in these patients. The overall score (P <
      0.01) and the subscale scores of acid reflux syndrome (P < 0.05), abdominal pain
      (P < 0.05), and indigestion syndrome (P < 0.01) in the Gastrointestinal Symptom
      Rating Scale were significantly improved by the 8-week RKT treatment.
      CONCLUSIONS: In the pilot study, patients with PPI-refractory NERD had disorders
      of esophageal and lower esophageal sphincter motility that were improved by RKT.
      Further studies examining esophageal motor activity of RKT in PPI-refractory NERD
      are required. University hospital Medical Information Network (UMIN) Clinical
      Trial Registry identifier: UMIN000003092.

PMID- 28761579
TI  - A Bayesian Approach for Population Pharmacokinetic Modeling of Alcohol in
      Japanese Individuals.
AB  - BACKGROUND: Blood alcohol concentration data that were previously obtained from
      34 healthy Japanese subjects with limited sampling times were reanalyzed.
      Characteristics of the data were that the concentrations were obtained from only
      the early part of the time-concentration curve. OBJECTIVE: To explore significant
      covariates for the population pharmacokinetic analysis of alcohol by
      incorporating external data using a Bayesian method, and to estimate effects of
      the covariates. METHODS: The data were analyzed using a Markov chain Monte Carlo
      Bayesian estimation with NONMEM 7.3 (ICON Clinical Research LLC, North Wales,
      Pennsylvania). Informative priors were obtained from the external study. RESULTS:
      A 1-compartment model with Michaelis-Menten elimination was used. The typical
      value for the apparent volume of distribution was 49.3 L at the age of 29.4
      years. Volume of distribution was estimated to be 20.4 L smaller in subjects with
      the ALDH2*1/*2 genotype than in subjects with the ALDH2*1/*1 genotype.
      CONCLUSIONS: A population pharmacokinetic model for alcohol was updated. A
      Bayesian approach allowed interpretation of significant covariate relationships,
      even if the current dataset is not informative about all parameters. This is the
      first study reporting an estimate of the effect of the ALDH2 genotype in a PPK
      model.

PMID- 28761580
TI  - Is Prostate Biopsy Recommended in Turkish Men with a Prostate-Specific Antigen
      Level between 2.5 and 4 ng/mL?
AB  - BACKGROUND: Prostate cancer is the most common solid tumor. The incidence of
      prostate cancer shows regional and racial differences. The ideal PSA threshold
      for prostate biopsy is still being debated. OBJECTIVE: We aimed to investigate
      cancer detection rates in Turkish men who underwent transrectal ultrasound-guided
      prostate biopsy (TRUSPB) who had prostate-specific antigen (PSA) levels in the
      range of 2.5 to 4.0 ng/mL and compare them with the rates of cancer in patients
      with PSA levels in the range of 4.0 to 10.0 ng/mL. METHODS: All Turkish men who
      underwent TRUSPB in our clinic between January 2012 and May 2014 were included;
      that is, 101 patients (Group 1) with PSA level in the range of 2.5 to 4.0 ng/mL
      and 522 patients (Group 2) with PSA level in the range of 4.0 to 10.0 ng/mL. Mean
      PSA level, age, prostate volume, and cancer detection rates were evaluated.
      RESULTS: The mean age was 60.5 and 64 years in Group 1 and Group 2, respectively
      (P = 0.06). The mean PSA level was determined as 3.1 and 6.8 ng/mL in Group 1 and
      Group 2, respectively (P = 0.03). The cancer detection rate was 12.7% in Group 1
      (n = 13) and 30.8% in Group 2 (n = 161), which revealed a statistically
      significant difference between the 2 groups (P = 0.001). In Group 1, 9 of 13
      patients (69%) had Gleason score of 6, 3 (23%) had Gleason score of 7, and 1 (8%)
      had a Gleason score of 8. CONCLUSIONS: The cancer detection rate is lower in
      Turkish men with PSA level in the range of 2.5 to 4.0 ng/mL when compared with
      men with PSA level in the range of 4.0 to 10.0 ng/mL. Furthermore, most patients
      in whom cancer was detected who have a PSA level in the range of 2.5 to 4.0 ng/mL
      are low risk. Therefore, the benefit of TRUSBP in Turkish men with PSA level
      between 2.5 and 4 ng/mL is low.

PMID- 28761581
TI  - Extended-Release Guaifenesin/Pseudoephedrine Hydrochloride for Symptom Relief in
      Support of a Wait-and-See Approach for the Treatment of Acute Upper Respiratory
      Tract Infections: A Randomized, Double-Blind, Placebo-Controlled Study.
AB  - BACKGROUND: Despite the well-known fact that antibiotics (AB) are not effective
      against viruses, many patients ask for - and all too often doctors provide - AB
      for treating URTIs. Over-prescribing of AB is one of the key causes for the
      development of bacterial resistance, which the U.S. Centers for Disease Control
      and Prevention (CDC) calls "one of the world's most pressing public health
      problems". In addition to the CDC initiated "Get Smart About Antibiotics"
      campaign, focused on educating doctors the public about the importance of
      appropriate AB use, other programs tackling this problem include the development
      of new treatment paradigms. Data published at the Oregon Health & Science
      University demonstrated that a 'wait-and-see' approach, without an AB
      prescription for the treatment of acute childhood ear infections, was as quick,
      safe, and effective in resolving the infections as an AB prescription (Spiro DM,
      Tay KY, Arnold DH, Dziura JD, Baker MD, Shapiro ED. Wait-and-See Prescription for
      the Treatment of Acute Otitis Media. JAMA 2006; 296:1235-1241). OBJECTIVE: To try
      and reduce inappropriate prescribing practices, a wait and see or delayed
      approach requires patients to return for a prescription if their symptoms persist
      or worsen. The aim of this study was to determine whether treatment with Mucinex
      D (Reckitt Benckiser LLC, Parsippany, New Jersey) lowers the use of antibiotics
      in the treatment of URTIs when compared with placebo. METHODS: Patients aged 18
      to 75 years with symptoms of acute URTIs were randomized to 1200 mg
      guaifenesin/120 mg pseudoephedrine hydrochloride extended-release, bilayer
      tablets or matching placebo for 7 consecutive days. Eligible patients met
      physician's criteria for antibiotic therapy but were considered suitable for a
      wait and see approach (withholding antibiotics for >=48 hours). Patients recorded
      symptom ratings via an interactive voice response system. RESULTS: One thousand
      one hundred eighty-nine patients enrolled; data are presented for the modified
      intent-to-treat population (n = 1179). At Day 8, significantly fewer patients
      receiving guaifenesin/pseudoephedrine versus placebo desired antibiotics (4.2% vs
      8.0%). No adverse effects were reported due to patients not taking antibiotics.
      Significant reductions in URTI symptoms were observed for extended-release
      guaifenesin/pseudoephedrine versus placebo, from Day 1 throughout the study;
      however, the proportion of patients experiencing overall relief at the Day 4
      evening assessment (primary end point) did not reach statistical significance.
      Treatment-related adverse events were reported in 9.8% and 4.7% of patients
      receiving guaifenesin/pseudoephedrine and placebo, respectively. CONCLUSIONS: The
      study found that a wait and see approach was associated with decreased antibiotic
      use. In addition, the use of a guaifenesin pseudoephedrine combination product
      provided an effective symptom control compared to a placebo and a well-tolerated
      first-line strategy for the management of URTIs. This study was not designed to
      assess the effects of guaifenesin or pseudoephedrine individually. Other
      limitations include the need for better clinical methods to assess the
      effectiveness of treatments for acute symptoms of patients with URTIs.
      ClinicalTrials.gov identifier: NCT01202279.

PMID- 28761582
TI  - Population Pharmacokinetic Characteristics of Amikacin in Suspected Cases of
      Neonatal Sepsis in a Low-Resource African Setting: A Prospective Nonrandomized
      Single-Site Study.
AB  - BACKGROUND: Amikacin exhibits marked pharmacokinetic (PK) variability and is
      commonly used in combination with other drugs in the treatment of neonatal
      sepsis. There is a paucity of amikacin PK information in neonates from low
      resource settings. OBJECTIVES: To determine the PK parameters of amikacin, and
      explore the influence of selected covariates, including coadministration with
      aminophylline, on amikacin disposition in neonates of African origin. METHODS:
      Neonates with suspected sepsis admitted to an intensive care unit in Accra,
      Ghana, and treated with amikacin (15 mg/kg loading followed by 7.5 mg/kg every 12
      hours), were recruited. Serum amikacin concentration was measured at specified
      times after treatment initiation and analyzed using a population PK modeling
      approach. RESULTS: A total of 419 serum concentrations were available for 247
      neonates. Mean (SD) trough amikacin concentration (from samples collected 30
      minutes before the fourth dose) among term (n = 25), and preterm (<37 weeks'
      gestation n = 36) neonates were 6.2 (3.4) and 9.2 (5.7) ug/mL, respectively (P =
      0.02). A 1-compartment model best fitted amikacin disposition, and birth weight
      was the most important predictor of amikacin clearance (CL) and distribution (V).
      The population CL and V of amikacin were related as CL (L/h) = 0.153 (birth
      weight/2.5)1.31, V (L) = 2.94 (birth weight/2.5)1.18. There was a high between
      subject variability (58.9% and 50.7%) in CL and V, respectively. CL and V were
      0.058 L/h/kg and 1.15 L/kg, respectively, for a mean birth weight of 2.1 kg, and
      the mean half-life (based on 1-compartment model), was 13.7 hours. CONCLUSIONS:
      The V and half-life of amikacin in this cohort varied from that reported in non
      African populations, and the high trough and low peak amikacin concentrations in
      both term and preterm neonates suggest strategies to optimize amikacin dosing are
      required in this population.

PMID- 28761583
TI  - Challenges of Empirical Antibiotic Therapy for Community-Acquired Pneumonia in
      Children.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity
      and mortality globally, responsible for more than 14% of deaths in children
      younger than 5 years of age. Due to difficulties with pathogen identification and
      diagnostics of CAP in children, targeted antimicrobial therapy is not possible,
      hence the widespread use of empirical antibiotics, in particular penicillins,
      cephalosporin, and macrolides. OBJECTIVES: This review aimed to address medical,
      societal, and political issues associated with the widespread use of empirical
      antibiotics for CAP in the United Kingdom, India, and Nigeria. METHODS: A
      literature review was performed identifying the challenges pertaining to the use
      of widespread empirical antibiotics for CAP in children. A qualitative analysis
      of included studies identified relevant themes. Empirical guidance was based on
      guidelines from the World Health Organization, British Thoracic Society, and
      Infectious Diseases Society of America, used in both industrialized and resource
      poor settings. RESULTS: In the United Kingdom there was poor adherence to
      antibiotics guidelines. There was developing antibiotic resistance to penicillins
      and macrolides in both developing and industrialized regions. There were
      difficulties accessing the care and treatment when needed in Nigeria. Prevention
      strategies with vaccination against Streptococcus pneumonia, Haemophilus
      influenza, and measles are particularly important in these regions. CONCLUSIONS:
      Effective and timely treatment is required for CAP and empirical antibiotics are
      evidence-based and appropriate in most settings. However, better diagnostics and
      education to target treatment may help to prevent antibiotic resistance. Ensuring
      the secure financing of clean food and water, sanitation, and public health
      infrastructure are also required to reduce the burden of disease in children in
      developing countries.

PMID- 28761584
TI  - Canadian Urological Association-Pediatric Urologists of Canada (CUA-PUC)
      guideline for the diagnosis, management, and followup of cryptorchidism.

PMID- 28761585
TI  - Early clamp release during laparoscopic partial nephrectomy: Implications for
      preservation of renal function.
AB  - INTRODUCTION: Intraoperative warm ischemic time (WIT), associated with hilar
      clamping during partial nephrectomy (PN), is an established modifiable risk
      factor for renal dysfunction. We assessed early clamp release (ECR) as a strategy
      to reduce WIT and assess its impact on renal function and bleeding. METHODS: We
      retrospectively assessed patients who underwent minimally invasive PN by a single
      surgeon at our centre since December 2011. Comparing the standard technique to an
      ECR modification, WIT, complications, change in estimated glomerular filtration
      rate (eGFR), and change in differential function as demonstrated by MAG-3 nuclear
      renography were assessed. Followup blood work and renograms were performed at 6
      12 weeks postoperatively and compared to baseline in 70 patients (35 ECR: 35
      control). RESULTS: The ECR and control groups were similar in age, sex, and
      tumour size, with only patient weight being higher in the ECR group (91.6 vs.
      81.6 kg; p<0.05). WIT was significantly lower in ECR group compared to control
      (18.8 vs. 31.5 minutes; p<0.05). Although there was no significant difference in
      change from baseline eGFR in the early postoperative period (Day 3) or in
      followup (6-12 weeks), the control group had a significantly greater loss of
      ipsilateral renal function from baseline compared to the ECR group (9 vs. 4%
      change; p<0.05). Blood loss and complication rate were similar between groups.
      CONCLUSIONS: The ECR technique offers a safe, reproducible alternative that
      reduces WIT during laparoscopic PN. ECR demonstrates a reduction in overall
      ipsilateral renal dysfunction, without increasing complication or intraoperative
      bleeding risk.

PMID- 28761586
TI  - Evolving attitudes toward robotic surgery among Canadian urology residents.
AB  - INTRODUCTION: Robotic-assisted laparoscopic surgery (RAS) has not been adopted as
      rapidly or widely in Canada as in the U.S. In 2011, Canadian urology residents
      felt that RAS represented an expanding field that could potentially negatively
      impact their training. We re-evaluate trainee exposure and attitudes to RAS in
      Canadian residency training five years later. METHODS: All Canadian urology
      residents were asked to participate in an online survey designed to assess
      current resident exposure to and perception of RAS. RESULTS: The response rate
      was 39% (61/157). Seventy-seven percent of residents reported being involved in
      at least one RAS procedure (52% in 2011), and the majority had exposure to <10
      cases. For those in hospitals with access to RAS, 96% desired more console time,
      while only 50% of those without access wanted more console experience. Of all
      residents, 50% felt that RAS will become the gold standard in certain urological
      surgeries (34% in 2011), but only 28% felt that RAS would play an increasingly
      important role in urology (59% in 2011). CONCLUSIONS: Despite an increase in
      exposure to RAS in residency programs over the past five years, console
      experience remains limited. Although these residents desire more access to RAS,
      many voice uncertainty of the role of RAS in Canada. We cannot conclude whether
      RAS is perceived by residents to be beneficial or detrimental to their training
      nationwide. Moving forward in the robotic era, it will be important to either
      modify residency curricula to address RAS experience or to limit RAS to
      fellowship training.

PMID- 28761587
TI  - Retrograde leak point pressure measurement improves outcomes of the Virtue male
      sling for postprostatectomy incontinence.
AB  - INTRODUCTION: We aimed to compare the efficacy of two different sling tensioning
      approaches, and to report our experience, including safety and impact on quality
      of life (QoL) of the Virtue(r) male sling for the treatment of postprostatectomy
      incontinence (PPI). METHODS: From our prospectively maintained database, we
      retrospectively identified all men treated with the Virtue male sling for PPI
      between March 2009 and February 2014 by two urologists in two institutions.
      Baseline demographic data and the sling tensioning method were abstracted from
      the database. Likewise, the Patient Global Impression of Improvement (PGI-I)
      scale, severity of incontinence, and clinical outcomes were also abstracted.
      RESULTS: 48 patients were treated with the Virtue quadratic male sling. Sling
      tensioning was done using cystoscopy in the first 18 patients (Group 1), while
      per-operative retrograde leak point pressure (RLPP) measurement was done in the
      last 30 patients (Group 2). The median (interquartile range [IQR]) followup from
      the day of surgery was 22 (15-41) months. At the last followup visit, 7 (39%)
      patients in Group 1 were cured or improved of their PPI, compared to 21 (70%)
      patients in Group 2 (p=0.03). The final median (IQR) RLPP in these patients was
      41 (37-48) cm H2O. Transient pain was the most common adverse event, occurring in
      23 (48%) of patients. Twenty-one (70%) patients in Group 2 were "much better" or
      "very much better" with their device, compared to 7 (39%) in Group 1 (p=0.0008).
      CONCLUSIONS: The Virtue male sling is a valuable treatment option for PPI. Per
      operative RLPP measurement significantly improves cure and satisfaction rates.

PMID- 28761588
TI  - Salvage prostatectomy for post-radiation adenocarcinoma with treatment effect:
      Pathological and oncological outcomes.
AB  - INTRODUCTION: Prostate biopsies following localized radiation therapy for
      prostate cancer often demonstrate residual prostatic carcinoma with treatment
      effect (CTE). The final oncological outcome of prostatic CTE is currently
      uncertain. We studied the pathological and oncological outcomes for a large
      cohort of patients who had CTE on post-radiation therapy biopsy and subsequently
      underwent salvage radical prostatectomy (SRP). METHODS: A single-centre
      retrospective review of all SRPs performed from 1995-2014 was performed. Cases
      were selected for this analysis if they had had a post-radiation "for-cause"
      biopsy. Biopsy results were compared to final pathology results following SRP.
      Pathological and clinical outcomes were compared by extent of treatment effect
      seen on the post-radiation biopsy. RESULTS: A total of 70 patients who had
      salvage prostatectomy at MD Anderson Cancer Centre from 2007-2015 met study
      criteria. CTE was found on biopsy in the absence of other adenocarcinoma in 16
      patients. Among them, one (7%) patient had no evidence of carcinoma at the time
      of salvage prostatectomy, four (27%) had CTE, three (20%) had adenocarcinoma with
      minimal or partial treatment effect (PTE), and seven (47%) had adenocarcinoma
      with no treatment effect (NTE). For those with CTE on biopsy, 69% had biochemical
      recurrence at a median time of 0.4 years (interquartile range [IQR] 0.22-1.52)
      vs. 52% for all patients (median 0.44 years, IQR 0.11-1.70) and 47% for those
      with no treatment effect (median 0.62 years, IQR 0.05-1.90). Metastasis developed
      after salvage prostatectomy in 11.8% of the whole cohort (8/68, median time to
      metastasis was 3.03 years, IQR 2.45-4.47), 26.7% of patients with CTE (median 3.2
      years, IQR 1.96-4.44), and 6.7% of patients with NTE (median 2.45 years, IQR 0.98
      2.86). Median recurrence-free survival was 2.78 years (95% confidence interval
      [CI] 0.84-5.43) for all patients, 0.51 years (95% CI 0.22-2.35) for those with
      CTE, and 4.95 years (95% CI 0.95-7.08) for those with NTE; the difference was not
      significant (p=0.13). On multivariate analysis, pre-SRP biopsy Gleason grade <7
      (hazard ratio [HR] 0.38; 95% CI 0.14-1.02) and number of biopsy cores positive
      for carcinoma (HR 1.11; 95% CI 1.00-1.22) were significant for prediction of
      cancer recurrence. CONCLUSIONS: Patients undergoing salvage prostatectomy for CTE
      or PTE demonstrated in a for-cause biopsy after radiation therapy had
      pathological evidence of viable, untreated cancer in more than 50% of cases and
      were at significant risk of adverse pathological features. Patients with CTE may
      therefore benefit from salvage radical prostatectomy. Our study is limited by its
      retrospective nature and sample size. More studies are required to further
      validate our findings and assess the benefit of SRP in this population.

PMID- 28761589
TI  - The role of urinary cytology when diagnostic workup is suspicious for upper tract
      urothelial carcinoma but tumour biopsy is nonconfirmatory.
AB  - INTRODUCTION: We sought to determine the value of obtaining preoperative urinary
      cytology when diagnostic workup of an upper tract mass is suspicious for upper
      tract urothelial carcinoma (UTUC), but biopsy fails to confirm the diagnosis.
      METHODS: Using billing code data, 239 patients were identified as having
      undergone radical nephroureterectomy (RNU) by 16 urologists from September 29,
      1998 to July 31, 2015. Of this group, 19 adult patients had a presumed
      preoperative diagnosis of UTUC in a native kidney, at least three months of
      followup, no history of concurrent radical cystectomy with RNU, and negative/non
      diagnostic tissue biopsy. These patients were divided into three groups: Group A
      had no urinary cytology taken (n=6); Group B had upper and/or lower tract
      cytology performed with neither positive nor atypical (n=7); Group C had upper
      and/or lower tract cytology performed with at least one positive or atypical
      (n=6). RESULTS: Demographic information and diagnostic workup was similar between
      the groups, although Group A had more patients with a history of prior radical
      cystectomy for bladder cancer (p=0.02). One patient in Group B had benign tissue
      on final pathology. All patients in Groups A and C had malignancy on final
      pathology and overall, the three groups had similar rates of malignancy.
      CONCLUSIONS: When a composite of clinical findings suggest UTUC, performing
      urinary cytology may not be necessary. A negative result in this setting should
      not be used to rule out UTUC, as this is often discordant with final pathology. A
      positive cytology result may help solidify the diagnosis when other findings are
      less clear.

PMID- 28761590
TI  - Conservative treatment of upper urinary tract carcinoma: Long-term results.
AB  - INTRODUCTION: We sought to assess the long-term results of conservative treatment
      for upper urinary tract carcinoma (UUTC) with regard to tumour recurrence and
      preservation of renal unit. METHODS: From October 1987 to January 2014, 65
      patients (median age 68 years) were diagnosed with UUTC and underwent endoscopic
      and open surgical techniques. Thirteen patients had bilateral disease and one had
      a single kidney. The primary approach was endoscopic in 37 reno-ureteral units
      (20 percutaneous resections, 17 ureteroscopies ). Open surgery was performed in
      19 cases. A total of 20 patients received mitomycin C. RESULTS: Superficial stage
      pTa or T1 was noted in 37 patients, infiltrating stage pT2 and pT3 in seven and
      inverted papilloma in one. The stage of the tumour was impossible to classify in
      20. With a median followup of 75.12 months (interquartile range [IQR] 144.71
      17.41), the kidney preservation, recurrence, specific survival, and global
      survival rates were 78.5% (51/65), 40.0% (26/65), 92.3% (60/65), and 69.2%
      (45/65), respectively. From the patients who had recurrence, 15 were salvaged
      with radical nephroureterectomy (RNU). The bladder tumour recurrence rate after
      the surgery was 30.76% (20/65). At the end of the followup, five patients had
      died of UUTC progression and 16 from other causes. Postoperative complications
      included one case of fistula, one case of stricture, and one case of nephrectomy
      due to bleeding. CONCLUSIONS: In selected cases, conservative management is a
      safe and feasible alternative to RNU, with the advantage of renal unit
      preservation.

PMID- 28761591
TI  - Ischemic priapism: Can eosinophil count and platelet functions be positive
      predictive factors in etiopathogenesis.
AB  - INTRODUCTION: We evaluated the relation between ischemic priapism (IP) and blood
      count parameters in IP patients. We especially wanted to examine the contribution
      of eosinophil count (EC), platelet count (PC), and mean platelet volume (MPV)
      values, which are suspected predictive parameters for vascular endothelium damage
      and venoocclusive pathogenesis and etiopathogenesis, particularly in IP. METHODS:
      A total of 40 IP patients fulfilled the study criteria. Forty healthy volunteers
      in a similar age group were included as the control group. Complete blood count
      values were compared between the two groups. Intergroup comparisons were
      performed using the Mann-Whitney U test, and the chi-square test was used to
      assess the relationship between categorical variables in the patient groups. The
      area under the curve was calculated by receiver operating characteristic (ROC)
      regression analyses. Epidemiological diagnosis percentages were calculated by
      finding cutoff values. RESULTS: The IP group's high MPV, PC, and EC values
      compared to those of the control group were detected to be statistically
      significant (p<0.001, p=0,03, p=0.001, respectively). No statistically
      significant difference was observed between the two groups for other blood count
      parameters. Statistically significant values for IP were measured as MPV:
      positive predictive value: 84%; EC: positive predictive value: 71.4%; and PC:
      positive predictive value: 61.4%. CONCLUSIONS: High MPV, PC, and EC values are
      significant positive predictive factors in IP etiopathogenesis. No proof was
      detected for other blood count parameters playing an active role in IP
      etiopathogenesis.

PMID- 28761592
TI  - A prospective audit on the effect of training and educational workshops on the
      incidence of urethral catheterization injuries.
AB  - INTRODUCTION: The incidence of iatrogenic urethral catheterization (UC) injuries
      is approximately 0.3%. Resultant complications are associated with patient
      morbidity and unnecessary healthcare costs. Our aim was to investigate whether
      educational training workshops decreased the incidence of UC-related injuries.
      METHODS: A prospective audit was performed to calculate incidence, morbidity, and
      costs associated with iatrogenic UC injury from January to July 2015. Educational
      workshops were then conducted with healthcare staff and training modules for
      junior doctors. UC-related incidence, morbidity, and costs in the subsequent six
      month period were recorded prospectively and compared with the previous data.
      RESULTS: The incidence of iatrogenic UC injuries was reduced from 4.3/1000
      catheters inserted to 3.8/1000 catheters after the intervention (p=0.59).
      Morbidity from UC increased in the second half in the form of increase in
      cumulative additional inpatient hospital stay (22 to 79 days; p=0.25), incidence
      of urosepsis (n=2 to n=4), and need for operative intervention (n=1 to n=2). The
      cost of managing UC injuries almost doubled in the period after the training
      intervention (?50 449 to ?90 100). CONCLUSIONS: Current forms of educational and
      training interventions for UC did not significantly change morbidity or cost of
      iatrogenic UC injuries despite a decrease in incidence. Improved and intensive
      training protocols are necessary for UC to prevent avoidable iatrogenic
      complications, as well as a safer urethral catheter design.

PMID- 28761593
TI  - Case series: Transplantation of kidneys from donors with renal artery aneurysm.
AB  - INTRODUCTION: With the present disparity between organ availability and recipient
      demands, we reported our experience in transplanting kidneys with renal artery
      aneurysm after back-table reconstruction. METHODS: Four patients were identified.
      The repair consisted of excision of the aneurysm with ostial closure, and for one
      of the cases, an ovarian vein patch was used. We reviewed the safety and outcomes
      of this procedure. All donors were asymptomatic before surgery and were diagnosed
      incidentally during living donor evaluation. The nephrectomies performed were
      hand-assisted laparoscopic approaches. All recipients had followup renal function
      and ultrasound duplex of renal artery at six and 12 months and then annually.
      RESULTS: The mean age of the recipients was 28.7 years (range 3-45). The mean
      size of the aneurysm was 7.4 +/- 2.7 mm. All patients had immediate graft
      function with median serum creatinine of 1.9 +/- 1.5 mg/dL at discharge. The
      average length of hospital stay was 6.25 +/- 2.6 days. They also maintained good
      renal function with an average estimated glomerular filtration rate (eGFR) of
      102.8 mL/min/1.73m2 (range 53.4-199 mL/min/1.73m2) and patent vessels at one
      year. One patient suffered from acute antibody-mediated rejection and lost his
      graft (medication non-compliance). One patient had two simultaneous benign renal
      cysts that were resected. Three of the kidneys were right-sided and one left.
      Mean cold ischemia time was 86 +/- 18 minutes. No deaths have been recorded.
      CONCLUSIONS: Transplanting kidneys with a renal artery aneurysm after ex-vivo
      repair is safe and the outcomes are encouraging. Also, it may play an important
      role in expanding the donor pool in the face of current organ shortage.

PMID- 28761594
TI  - Case series: Bladder clot evacuation using a prostate morcellation device.
AB  - INTRODUCTION: We sought to provide a technical update on the use of a prostate
      morcellator device (PMD) to manage organized blood clots of the bladder following
      laser prostatectomy. METHODS: Herein, we describe our experience in using the
      Wolf Piranha morcellator in managing organized bladder blood clots supplemented
      with a retrospective chart review of the patients in whom this procedure was
      performed. RESULTS: Six patients, all male with a mean age of 75 +/- 8.9 years,
      had organized bladder clots following either holmium laser enucleation or
      photoselective vaporization of the prostate managed with a PMD. Clots were
      recognized based on hematuria or urinary retention a median of 3.5 days following
      the aforementioned procedures. Initial management was attempted with more
      conservative measures, including a three-way Foley catheter, followed by
      cystoscopy with an Ellik evacuator, or a glass Tommey syringe. Morcellation times
      were a mean of 10.2 +/- 6.15 minutes (range 2-18). This technique was able to
      manage clots that were an average of 173.3 +/- 115.9 cc in size. The procedure
      was well-tolerated. No patients experienced intraoperative or morcellator-related
      complications. CONCLUSIONS: Benign prostatic hypertrophy frequently requires
      surgical endoscopic management and can be complicated by hematuria and bladder
      blood clot formation. When these clots become organized, this can lead to urinary
      retention and the required management, evacuation, may be difficult. The use of a
      Wolf Piranha PMD is a safe, well-tolerated, and effective in evacuating organized
      blood clots of the bladder.

PMID- 28761595
TI  - Case: Spontaneous regression of post-radical prostatectomy prostate-specific
      antigen elevation without adjuvant therapy in a patient with lymph node
      metastasis.
AB  - Prostate cancer remains the most frequently diagnosed cancer among men. The
      combination of clinical stage, serum prostate-specific antigen (PSA), and Gleason
      score (biopsy) assists in predictive assessment of pathological stage and
      prognosis. Furthermore, pathological criteria, including Gleason score, surgical
      margin status, extracapsular extension, seminal vesicle invasion, and lymph node
      involvement, provide prognostication in patients undergoing radical prostatectomy
      (RP). In this paper, we present a case of a patient with high-risk prostate
      cancer with persistent PSA elevation post-RP who experiences a complete
      regression of PSA without any adjuvant therapy. To the authors' knowledge, such a
      finding has not been described in the literature previously.

PMID- 28761596
TI  - Case: Incidental 18F-fluorodeoxyglucose-positron emission tomography/computed
      tomography prostate uptake: How should these patients be managed?

PMID- 28761597
TI  - Techniques: Utility of a 3D printed bladder model for teaching minimally invasive
      urethrovesical anastomosis.

PMID- 28761598
TI  - Correction to author list.
AB  - [This corrects the article on p. E142 in vol. 11, PMID: 28503229.][This corrects
      the article on p. E248 in vol. 11, PMID: 28503243.].

PMID- 28761599
TI  - Factors associated with severe malaria among children below ten years in Mutasa
      and Nyanga districts, Zimbabwe, 2014-2015.
AB  - INTRODUCTION: Severe malaria is a rare life threatening illness. Only a small
      proportion of patients with clinical malaria progress to this medical emergency.
      On reviewing 61 malaria death investigation forms submitted to the provincial
      office in 2014, 22(36%) were children below ten years who succumbed to severe
      malaria. Mutasa and Nyanga Districts reported 73% of these deaths. This study was
      conducted to determine factors associated with severe malaria so as to come up
      with evidence based interventions to prevent severe malaria and associated
      mortality. METHODS: A 1:2 unmatched case control study was conducted. A case was
      defined as a child 10 years and below, who was admitted at Hauna (Mutasa) or
      Nyanga District Hospitals between September 2014 and May 2015 with a primary
      diagnosis of severe malaria. Controls were children of similar age with
      uncomplicated malaria. Permission to conduct the study was sought and granted by
      the Medical Research Council of Zimbabwe (Approval number B/874), Joint Research
      Ethics Committee, Health Studies Office and the Manicaland Directorate
      Institutional Review Board. Written informed consent was sought from all
      caregivers of enrolled children. Interviewer administered questionnaires were
      used to ascertain exposures. RESULTS: A total of 52 cases and 104 controls were
      enrolled into the study. The median age of cases was 4 years (Q1=3, Q3=9) and 6
      years for controls (Q1=3, Q3=8). The Case Fatality Rate among cases was 28.8%.
      The independent risk factors for severe malaria were; distance >10km to the
      nearest health facility [Adjusted Odds Ratio (aOR)=14.35, 95% CI=1.30, 158.81],
      duration of symptoms before seeking medical care >2 days [aOR=9.03, 95% CI=2.21,
      36.93], having comorbidities [aOR=5.38, 95% CI=1.90, 15.19], staying in a house
      under construction [aOR=4.51, 95%CI=1.80, 11.32] and duration of illness before
      receiving antimalarial medicines >24 hours [aOR=3.82, 95% CI=1.44, 10.12]. Owning
      at least one ITN in the household [aOR=0.32, 95% CI=0.11, 0.95] and having a
      mother as a caregiver [aOR=0.23, 95% CI=0.09, 0.76] were independently protective
      of severe malaria. Being undernourished [Odds Ratio (OR)=10.13, 95% CI=1.04,
      98.49] and being female [OR=0.27, 95% CI=0.08, 0.96] were associated with
      mortality owing to severe malaria. CONCLUSION: Factors associated with severe
      malaria and mortality owing to severe malaria identified in this study are
      consistent with other studies. Caregiver healthcare seeking behaviours, patient
      related factors and health system related factors are important determinants of
      severe malaria among children. There is need for regular health education
      campaigns emphasizing on malaria prevention, signs and symptoms and benefits of
      seeking medical care immediately for sick children.

PMID- 28761601
TI  - Childhood tuberculosis: management and treatment outcomes among children in
      Northwest Ethiopia: a cross-sectional study.
AB  - INTRODUCTION: Childhood tuberculosis (TB) treatment is becoming a major challenge
      in the TB control efforts of the Ethiopian health system. This study assessed
      childhood tuberculosis management, and treatment outcomes among children who
      completed anti-TB treatment in Northwest Ethiopia. METHODS: A cross-sectional
      study was conducted among children who completed their anti-TB treatment in
      Gondar University Referral Hospital and 6 satellite health centers. Data from
      each child with tuberculosis were obtained from review of medical records. P
      values < 0.05 were considered statistically significant. RESULTS: The commonest
      method of childhood TB diagnosis was clinical assessment combined with chest x
      ray (48.5%). Absence of compliance with TB treatment guideline (98.7%), providing
      inadequate anti-TB regimen (1.8%), and poor adherence to treatment (22.5%) were
      challenges in management of childhood tuberculosis. Treatment success rate was
      78.9%. In the bivariate regression, factors associated with TB treatment outcomes
      were permanent residence (OR=8.3, 95%CI: 4.1, 16.7), antiretroviral therapy
      (OR=4.5, 95%CI: 1.2, 16), and adherence to treatment (p < 0.001). After
      controlling for confounders, adherence to anti-TB treatment (OR=0.003, 95% CI:
      0.001, 0.02) was independent predictor of treatment success. CONCLUSION: Anti
      tuberculosis treatment success rate was still low among children in Northwest
      Ethiopia. The health centers and hospital shall enhance strong follow-up of
      children on anti-tuberculosis treatment to improve treatment success with focus
      on rural children.

PMID- 28761602
TI  - [Papules on the back of hands: granuloma annulare should be suspected].

PMID- 28761600
TI  - [Evaluation of Knowledge-Attitudes-Practices of the populations in the health
      districts of Benoye, Laoukassy, Moundou and South N'Djamena towards canine rabies
      in Chad].
AB  - INTRODUCTION: Canine rabies remains a concern in Africa as well as in Chad. Our
      study aimed to evaluate the knowledge, attitudes and practices of the populations
      towards the appropriate management of people exposed to canine rabies and
      effective fight against it. METHODS: We conducted a cross-sectional, descriptive
      study in four health districts in Chad in July and in September 2015. Data were
      collected from households recruited by three-stage random sampling by means of a
      questionnaire. RESULTS: We conducted a survey of 2428 individuals having
      completed at least primary education level (54,12%). The average age was 36 +/-
      13.50 years. Surveyed individuals were farmers (35,17%), merchants (18,04%),
      households (12.81%). Rabies was defined as a disease transmitted from the dog to
      the man (41.43%), an alteration in brain function (41.27%), an undernourishment
      (10.26%). The cat was little-known to be a reservoir(13.84%) and a vector
      (19,77%) as well as licking was little-known to be a transmission medium (4.61%)
      and cat vaccination to be a preventive measure (0.49%). First aid for a bite at
      home was the traditional practice (47,69%), wounds washing (19.48%) or no action
      undertaken (20.43%). Households consulted the Health Service (78.50%), the Animal
      Health Service (5.35%) and the traditional healers (27%). CONCLUSION: A
      communication campaing for implementing first aid at home in the event of a bite,
      knowledge about the cat as a reservoir and a vector and licking as a transmission
      medium as well as the promotion of the consultation of veterinary services in the
      event of a bite are necessary.

PMID- 28761603
TI  - [Malignant non-hodgkin's lymphoma of the breast and HIV: about a case].
AB  - Malignant non-Hodgkin's lymphoma (NHL) accounts for 0.5% of all breast cancers.
      Diagnosis is essentially based on histology. We report the case of a 42-year old
      female patient with MNHL of the breast and positive HIV serology. This study
      aimed to highlight the clinical, radiological and therapeutic aspects of this
      disease and to emphasize the importance of HIV testing in patients with
      extraganglionar MNHL.

PMID- 28761605
TI  - Henoch-Schonlein purpura associated with primary active Epstein-Barr virus
      infection: a case report.
AB  - Henoch-Schonlein purpura (HSP) is the most common form of childhood vasculitis.
      Various viral and bacterial infections, drugs, vaccines, food allergy and even
      insect bites have been considered as triggering factors in pathogenesis of HSP.
      Epstein-Barr virus (EBV) infection, which is associated with HSP, have been
      rarely reported. Herein we present HSP patient possibly caused by EBV infection.
      A 8-year old boy was admitted to our department with fever, rashes on legs and
      arms and intermittent mild abdominal pain. Multiple purpuric rashes were on his
      extremities, abdomen and buttock. Laboratory investigations revealed that
      monospot test was positive, EBV serology tests; Anti-EA-D Ig G: 3+, Anti-VCA
      gp125 Ig G: 3+, Anti-VCA p19 Ig M: 2+, Anti EBNA-1 Ig M: negative, Anti EBNA-1 Ig
      M: negative, Anti EBNA-1 Ig G: negative. The patient was interpreted as the
      primary active acute EBV infection. A skin biopsy showed leucocytoclastic
      vasculitis. The other viral and bacterial investigations were negative. The
      patient was diagnosed as HSP vasculitis according to EULAR criteria and treated
      with intravenous hydration and ibuprofen. He was discharged after 15 days with
      normal laboratory findings and physical examination. We think that EBV infection
      may be stimulant factor for autoimmune reactions and may cause HSP vasculitis.
      Hence, it may be useful to investigate the EBV infection in etiology of HSP
      cases.

PMID- 28761604
TI  - [Colon adenocarcinoma and synchronous type 1 papillary renal cell carcinoma: a
      unique association].
AB  - The detection of primary tumors synchronous with colorectal cancer has been the
      subject of multiple publications. This association can occur sporadically or fall
      under the framework of well defined clinical syndromes such as Lynch syndrome.
      Synchronous association of colorectal cancer (CRC) and renal cell carcinoma is
      rare. It is even more rare when renal cell carcinoma is of papillary origin, with
      only 2 cases reported in the literature. The association between CRC and renal
      cell carcinoma does not seem to be related to mismatch repair proteins (MMR)
      abnormality and does not include, up to now, any clinical syndrome. We report the
      case of a 69-year old woman with colorectal cancer associated with synchronous
      type 1 papillary renal cell carcinoma unexpectedly detected during screening for
      CRC. We here discuss the pathogenesis as well as the prognosis of this rarely
      described entity.

PMID- 28761606
TI  - Malaria morbidity and mortality trends in Manicaland province, Zimbabwe, 2005
      2014.
AB  - INTRODUCTION: Zimbabwe targets reducing malaria incidence from 22/1000 in 2012 to
      10/1000 by 2017, and malaria deaths to near zero by 2017. As the country moves
      forward with the malaria elimination efforts, it is crucial to monitor trends in
      malaria morbidity and mortality in the affected areas. In 2013, Manicaland
      Province contributed 51% of all malaria cases and 35% of all malaria deaths in
      Zimbabwe. This analysis describes the trends in malaria incidence, case fatality
      and malaria outpatient workload compared to the general outpatient workload.
      METHODS: We analyzed routinely captured malaria data in Manicaland Province for
      the period 2005 to 2014. Epi Info version 7 was used to calculate chi-square
      trends for significance and Microsoft Excel was used to generate graphs.
      Permission to analyze the data was sought and granted by the Provincial Medical
      Directorate Institutional Review Board of Manicaland and the Health Studies
      office. RESULTS: Malaria morbidity data for the period 2005-2014 was reviewed and
      a total of 947,462 cases were confirmed during this period. However, malaria
      mortality data was only available for the period 2011-2014 and cumulatively 696
      deaths were reported. Malaria incidence increased from 4.4/1,000 persons in 2005
      to 116.3/1,000 persons in 2014 (p<0.001). The incidence was higher among females
      compared to males (p-trend<0.001) and among the above five years age group
      compared to the under-fives (p-trend<0.001). The proportion of all Outpatient
      Department attendances that were malaria cases increased 30 fold from 0.3% in
      2005 to 9.1% in 2014 (p-trend<0.001). The Case Fatality Rate also increased 2
      fold from 0.05 in 2011 to 0.1 in 2014 (p-trend<0.001). CONCLUSION: Despite
      current malaria control strategies, the morbidity and mortality of malaria
      increased over the period under review. There is need for further strengthening
      of malaria control interventions to reduce the burden of the disease.

PMID- 28761607
TI  - [Severe ventricular arrhythmias in a patient with dilated cardiomyopathy and
      automated implantable defibrillator (AID)].
AB  - Severe ventricular arrhythmias are frequent during heart failure; they are a life
      threatening condition due to the increased risk of sudden death. Efficient
      management remains limited in sub-Saharan Africa because of the limited or
      unavailable medical resources as automated implantable defibrillator (AID). We
      report the case of a 56-year old patient with non ischemic dilated cardiomyopathy
      with very low left ventricular ejection fraction (LVEF)who underwent AID
      implantation for primary prevention of sudden cardiac death due to ventricular
      arrhythmias in 2012. Maintenance therapy combined diuretic, angiotensin
      converting enzyme (ACE) inhibitor and anti-vitamin K. In the month of November
      2014 the patient had iterative episodes requiring the delivery of electric shocks
      by the AID, without the sensation of palpitations suggestive of episodes of
      arrhythmias. Clinical examination is a poor screening test, especially for heart
      failure. AID detected multiple episodes of tachycardia and ventricular
      fibrillation justifying antitachycardia pacing (ATP) therapy or the delivery of
      electric shocks of 15J. The patient was treated with amiodarone and beta blocker.
      Evolution was favorable at 3-months follow-up. The patients had resumed normal
      activities, without experiencing new episodes requiring the delivery of electric
      shocks. This study emphasizes the essential role of anti-arrhythmic drug therapy
      for severe ventricular arrhythmias, even in the presence of AID.

PMID- 28761608
TI  - Knowledge of direct obstetric causes of maternal mortality and associated factors
      among reproductive age women in Aneded woreda, Northwest Ethiopia; a cross
      sectional study.
AB  - INTRODUCTION: in Ethiopia, 20,000 women die each year from complications related
      to pregnancy and childbirth with much more maternal morbidity occurring for each
      maternal death. Good knowledge of women related with direct causes of maternal
      mortality is important in reducing maternal morbidity and mortality. Therefore,
      the aim of this study was to assess knowledge of direct obstetric causes of
      maternal mortality and associated factors among reproductive age of women in
      Aneded woreda, Northwest Ethiopia. METHODS: A community-based cross-sectional
      study was conducted using multi-stage sampling followed by simple random sampling
      technique. The study was conducted in Aneded woreda, Northwest Ethiopia. A total
      of 844 reproductive age women were included in the study. Pre-tested semi
      structured questionnaire was used to collect the data. Data was collected through
      face-to-face interviews by 12 data collectors. Data was cleaned, coded and
      entered into Epi-data, then exported and analyzed using SPSS software. Bivariate
      and multivariable logistic regression analysis were computed to identify factors
      related to knowledge of obstetric causes of maternal mortality. The crude and
      adjusted odds ratios together with their corresponding 95% confidence intervals
      (CI) were computed. A P-value less than 0.05 was used to declare statistical
      significance. RESULTS: This study found that almost half (49.6%) of respondents
      have good knowledge level towards obstetric causes of maternal mortality.
      Significant variables associated with knowledge towards obstetric causes of
      maternal mortality were; being government employee (AOR=3.6, 95% CI=1.4-8.9),
      respondents who had additional monthly income from family members (AOR=1.54, 95%
      CI=1.04-2.27), respondents who attended primary school and above (AOR=1.6, 95%
      CI=1.13-2.25), distance of health facility in which the time it took less than 20
      minutes (AOR=2.25, 95% CI(1.24-4.09), 20-39minutes (AOR=3.06, 95% CI=1.66-5.64),
      40-60 minutes (AOR=2.38, 95% CI=1.52-5.26), and previous history of prolonged
      labor (AOR=1.4, 95% CI=1.04 -2.03) were the significant variables. CONCLUSION:
      This study indicated that the reproductive age women in the study area had poor
      knowledge towards about obstetric causes of maternal mortality. Therefore, to
      improve maternal knowledge and thereby reduce maternal death, the identified
      significant factors should be addressed through maternal and child health
      services. Designing appropriate strategies including the provision of targeted
      information, education, and communication is important.

PMID- 28761609
TI  - Evaluation of severe malaria case management in Mazowe District, Zimbabwe, 2014.
AB  - INTRODUCTION: Malaria is a preventable and curable disease. Mazowe district had
      been experiencing a lower malaria transmission rate in comparison to other
      districts in the Mashonaland Central province but it experienced a huge outbreak
      in the 2013-2014 rainy seasons with a case fatality rate (CFR) of 0.21%. This CFR
      was the highest in the province and it was twice as much as the national CFR
      (0.12%) for the same period. We evaluated severe malaria case management in
      Mazowe district to determine if practice is as per standard treatment guidelines.
      METHODS: A descriptive cross sectional study was conducted in Mazowe district
      using the Logical Framework approach. District Health Executives (DHE) members,
      nurses and severe malaria case notes were purposively and conveniently selected
      into the study. Key informant Interviews and review of case notes were carried
      out. All data were analysed using Epi Info 3.5.1.to calculate means and
      frequencies. Permission to conduct the study was obtained from the Mashonaland
      Central Provincial Medical Directorate (PMD) Institutional Ethical Review Board
      (IRB). RESULTS: The median age in years of the cases was 16 (Q1=7.3; Q3=30.8) and
      up to 58.1% of the cases were female. Inputs including staff, medicines and
      medical and laboratory equipment for severe case management were inadequate in
      the district. Only 60% of severe cases were diagnosed using blood slides and up
      to 95.6% of cases presented with one or more of the clinical signs of severe
      malaria. All severe cases were treated using correct anti-malarial and analgesic
      doses. Patient monitoring was not done as per prerequisite intervals and up to 5%
      of cases died. The health workers had above average knowledge on severe malaria.
      CONCLUSION: Severe malaria case management inputs were inadequate in the
      district. For many cases, the district did not follow complicated malaria
      treatment guidelines for diagnosis, treatment and monitoring. Untrained staff
      needs training in Severe Malaria Case Management and monitoring of commodity
      stocks needs to be strengthened.

PMID- 28761610
TI  - Cold chain management practices of health care workers in primary health care
      facilities in Southern Nigeria.
AB  - INTRODUCTION: Vaccination has caused a dramatic reduction in the threat of
      diseases that were once widespread and often times fatal. The efficient practice
      of cold chain management is therefore key to ensuring that the benefits of
      vaccination are sustained. The objective of this study is to assess the practice
      of cold chain management among health workers in primary health care facilities
      in Benin City, Edo State. METHODS: A descriptive cross-sectional study design was
      employed in this study. The study population consisted of registered nurses,
      auxiliary nurses and community health extension workers in primary health care
      facilities in Benin City, Edo State. The tool for data collection was pre-tested,
      structured self-administered questionnaire. Bivariate analysis between socio
      demographic variables and practice of cold chain management was done. Binary
      logistic regression was also done to determine significant predictors of practice
      of cold chain management. The level of significance was set at p < 0.05 for all
      associations. RESULTS: A total of 425 respondents participated in this study.
      Over two-thirds of respondents 314 (73.9%) had good practice of cold chain
      management. Significant determinants of practice of cold chain management were
      cold chain management training (p = 0.004), presence of functional refrigerators
      (p = 0.016), NPI supervision (p < 0.001) and higher level of education (p <
      0.001). CONCLUSION: The practice of cold chain management among respondents was
      fair. All stakeholders should ensure they work collectively towards ensuring that
      favorable environments which would improve the practice among health workers are
      put in place.

PMID- 28761611
TI  - [Literature review on human influenza epidemics occurred before the
      implementation plan for sentinel surveillance program in the DRC].
AB  - In the Democratic Republic of the Congo (DRC), several influenza epidemics are
      ignored because they are confused with other infectious diseases which have
      similar symptoms. Our study aims to assess influenza epidemics occurred in the
      DRC before 2008, year of the implementation of the influenza surveillance program
      in the DRC. We searched all the documents [articles, report,...] about influenza
      epidemic or acute respiratory infections [ARI] in the DRC before 2008 by using
      chosen key words. Epidemic description elements were identified and analyzed in
      each report. 4 documents have been found that had no article published. The sites
      of the epidemic outbreak were the rural health zones in Koshibanda and Kahemba,
      Bandundu [1995 and 2007], in Bosobolo, Equator [2002] and in Kinshasa [2002
      2003]. Attack and lethality rates were 3.9% and 16% in Koshibanda respectively;
      0.1% and 2% in Kinshasa; 47.5% and 1.5% in Bosobolo and 14.6% and 2.9% in
      Kahemba. Children less than 5 years of age were the most affected. Their attack
      rates ranged between 22.6 and 57.7% and lethality rates ranged between 3.2 and
      3.7%. The two epidemics in Bosobolo and Kinshasa were associated with H3N2
      influenza virus. This literature review highlights a high morbidity and mortality
      due to rare influenza epidemics in the DRC.

PMID- 28761612
TI  - [Medical oncology: is it a new medical speciality in Africa?]
AB  - Cancer is a major public health problem in Africa. Advances in the treatment of
      cancers over the last decade are undeniable. Multidisciplinary approach is
      essential for improved patient's management. Medical oncology is a recently
      recognized speciality in Africa Indeed, many African countries do not have
      doctors or a sufficient number of doctors qualified to practice in this medical
      specialty. The fight against cancer in Africa involves oncology speciality
      training and the development of curricula in order to ensure optimum patient
      management.

PMID- 28761613
TI  - [DRESS syndrome secondary to antituberculosis drugs: about a case].
AB  - Drug hypersensitivity syndrome or Drug Rash with Eosinophilia and Systemic
      Symptoms or DRESS syndrome is a severe and potentially life-threatening
      toxidermia. It should be suspected in patients developing cutaneous reaction
      following drug intake. We report the case of a 45-year old patient treated for
      pulmonary tuberculosis (TPM+) who developed DRESS syndrom induced by
      antibacillaries.

PMID- 28761615
TI  - [Historical buttock tumor: a case report].

PMID- 28761614
TI  - [Impact of Controlled Temperature Chain (CTC) approach on immunization coverage
      achieved during the preventive vaccination campaign against meningitis A using
      MenAfriVac in Togo in 2014].
AB  - METHOD: We conducted a survey from 9 to 14 March 2015 (for approximately 3
      months) after the end of the vaccination campaign in these four regions.
      Interviewees were selected using two stages cluster sampling stratified according
      to the regions. MenAfriVac vaccine in Controlled Temperature Chain (CTC) was used
      in 10 districts, in Togo. RESULTS: A total of 2707 households were surveyed and
      9082 people aged 1-29 years were interviewed. The average age of the individuals
      surveyed was 11.8+/-7.7 years and sex-ratio (H/F) was 1.01. The average number of
      individuals per household was 5.7 and that of persons aged 1-29 years targeted in
      the campaign was 3.4. Out of 9082 people surveyed 8889 (98%) were vaccinated.
      Multivariate analysis showed that the factors associated with immunization
      coverage using MenAfrivac vaccine were: habitual residence in the area at the
      time of the campaign (AOR = 4.52; 95%CI = [4.07 - 4.97]) and level of information
      about the campaign before it starts (AOR=2.42; 95%CI = [2.05 - 2.80]). By
      contrast, there were no differences in vaccination coverage between the areas
      based on whether the CTC approach was used or not (AOR=0.09; 95%CI = [-0.27 -
      0.45]). Two hundred and seven respondents (2.3%) reported that they had Adverse
      Event Following Immunisation (AEFI) after the administration of the vaccine.
      These were usually minor AEFI involving fever, abscesses and swelling at the
      injection site. CONCLUSION: Survey results show that the use of CTC in a country
      with limited resources such as Togo doesn't have a negative impact on
      immunization coverage. Indeed, there was no difference between immunization
      coverage in CTC and non-CTC areas. It is important to capitalize on the
      experience gained in order to use vaccines by Expanded Program of Immunization in
      CTC approach especially in countries with limited resources in terms of cold
      chain availability.

PMID- 28761616
TI  - Cardiometabolic risk among HIV-POSITIVE Ugandan adults: prevalence, predictors
      and effect of long-term antiretroviral therapy.
AB  - INTRODUCTION: We investigated the prevalence, predictors of and effect of
      Antiretroviral Therapy (ART) regimen on cardiometabolic risk among HIV-positive
      Ugandan adults at enrolment into a prospective cohort to study the Complications
      of Long-Term ART (CoLTART). METHODS: We collected data on cardiometabolic risk
      factors including dyslipidemia, hypertension, hyperglycemia, obesity and
      calculated the mean atherogenic index for Plasma (AIP) and 10 year Framingham
      risk score (FHS). Exposures were: ART regimen, duration on ART, demographic,
      socio-economic, behavioral, and life-style factors including smoking, physical
      activity and diet (including fruit and vegetables consumption). RESULTS: We
      enrolled 1024 participants, 65% female, mean age was 44.8 years (SD 8.0) and
      median duration on ART was 9.4 years (IQR 6.1-9.8). The prevalence of abdominal
      obesity was 52.6%, BMI>=25 kg/m2 -26.1%, hypertension-22.6%, high AIP-31.3% and
      FHS above 10% was 16.6%. The prevalence of low High Density Lipoprotein (HDL) was
      37.5%, high Total cholesterol (Tc)-30.2%, high Low Density Lipoprotein (LDL) 
      23.6%, high Triglycerides (TG)-21.2%, low physical activity-46.4% and alcohol
      consumption-26.4%. In multivariate linear regression analyses, increasing age was
      associated with higher mean Tc, HDL, LDL, FHS (P<0.001) and hyperglycemia
      (p<0.005). In multivariate logistic regression analyses, Protease Inhibitor (PI)
      containing regimens were significantly associated with higher risks of abnormal:
      Tc, LDL, TG, AIP, abdominal obesity, hypertension, low HDL and lower risk of a
      FHS >10% compared to the non PI regimen. CONCLUSION: ART increases
      cardiometabolic risk. Integration of routine assessment for cardiometabolic risk
      factors and preventive interventions into HIV care programs in resource-limited
      settings is recommended.

PMID- 28761617
TI  - Hepatocellular carcinoma: a clinicopathological study of 64 cases.
AB  - Hepatocellular carcinoma (HCC) is the most common of all liver cancers and is a
      major worldwide public health problem. The aim of this study was to provide an
      updated overview on clinicopathological features, treatment and outcome of HCC.
      In our retrospective study, we reviewed 64 cases of HCC that were diagnosed at
      the pathology department of Mongi Slim hospital over a fifteen-year period (2000-
      2014). Relevant clinical information and microscopic slides were retrospectively
      reviewed. Our study group included 38 men and 26 women (sex ratio M/F = 1,26)
      aged between 8 and 83 years (mean = 56,64 years). The presenting clinical
      symptoms were dominated by abdominal pain (n=34), followed by altered general
      health (n=25) and jaundice (n=4). Fifty-five patients underwent surgical
      treatment. Liver transplantation was performed in two cases and transarterial
      chemoembolization was achieved in seven cases. Histopathological examination of
      the surgical or biopsy specimen established the diagnosis of conventional HCC in
      55 cases, fibrolamellar carcinoma in 6 cases and clear cell HCC in 3 cases. Seven
      patients with HCC died postoperatively. Local recurrence of the tumour occurred
      in three cases and two patients had distant metastases postoperatively. The other
      patients are still being followed-up. Hepatocellular carcinoma is associated with
      a high rate of mortality because of early invasion, widespread metastasis and
      lack of effective therapeutic modalities. Accurate diagnosis and staging of these
      tumours is critical for optimal treatment planning and for determining prognosis.

PMID- 28761618
TI  - Percutaneous placement of the peripheral catheter to the subclavian vein for a VA
      shunt.
AB  - Hydrocephalus is a common neurosurgical pathology that affects people of all ages
      and especially the pediatric population. It can be very often a life threatening
      condition that pediatric neurosurgeons must deal with. Therefore a number of CSF
      diversion techniques have been established. The gold standard treatment currently
      is the placement of a ventriculo-peritoneal shunt. Because of hydrocephalus being
      a lifelong condition, it is almost in daily practice dealing with cases of shunt
      failures for a number of reasons. Herewith we present a 4 year old child with
      multiple ventriculo-peritoneal shunt revision surgeries and ventriculo-atrial
      failure due to distal catheter malfunction that was treated with percutaneous
      placement of the peripheral catheter in the subclavian vein.

PMID- 28761619
TI  - Ectopic thyroid tissue: unusual differential diagnosis of cervical paraganglioma.
AB  - Ectopic thyroid tissue (ETT) lateral to the midline is rare. Its occurrence in
      the carotid bifurcation is exceptional. We present a 45 years woman who consulted
      with a slow growing right cervical swelling. Clinical examination
      Ultrasonography, contrast enhanced CT and cervical MRI concluded to a
      paraganglioma. Intra-operatively, the tumor didn't have the characteristic aspect
      of a paraganglioma. Complete excision was performed. Histology concluded to an
      ectopic micro-vesicular thyroid adenoma.Previous literature was reviewed to
      summarize clinical and radiologic characteristics of such rare entity. Despite
      its rarity, ETT must be included in the differential diagnosis of cervical
      paraganglioma.

PMID- 28761620
TI  - [Swelling of the pectoralis muscle revealing isolated muscular tuberculosis].
AB  - Soft tissue tuberculosis is one of the rare forms of extrapulmonary tuberculosis.
      Furthermore, isolated muscular tuberculosis is exceptional. We here report the
      original case of a young immunocompetent patient with isolated muscular
      tuberculosis involving major pectoralis muscle. The diagnosis was mainly based on
      histology. The patient was successfully treated with anti bacterial therapy only.
      This rare case study has been combined with a literature review.

PMID- 28761621
TI  - Toxicity and Immunogenicity in Murine Melanoma following Exposure to Physical
      Plasma-Derived Oxidants.
AB  - Metastatic melanoma is an aggressive and deadly disease. Therapeutic advance has
      been achieved by antitumor chemo- and radiotherapy. These modalities involve the
      generation of reactive oxygen and nitrogen species, affecting cellular viability,
      migration, and immunogenicity. Such species are also created by cold physical
      plasma, an ionized gas capable of redox modulating cells and tissues without
      thermal damage. Cold plasma has been suggested for anticancer therapy. Here,
      melanoma cell toxicity, motility, and immunogenicity of murine metastatic
      melanoma cells were investigated following plasma exposure in vitro. Cells were
      oxidized by plasma, leading to decreased metabolic activity and cell death.
      Moreover, plasma decelerated melanoma cell growth, viability, and cell cycling.
      This was accompanied by increased cellular stiffness and upregulation of zonula
      occludens 1 protein in the cell membrane. Importantly, expression levels of
      immunogenic cell surface molecules such as major histocompatibility complex I,
      calreticulin, and melanocortin receptor 1 were significantly increased in
      response to plasma. Finally, plasma treatment significantly decreased the release
      of vascular endothelial growth factor, a molecule with importance in
      angiogenesis. Altogether, these results suggest beneficial toxicity of cold
      plasma in murine melanomas with a concomitant immunogenicity of potential
      interest in oncology.

PMID- 28761622
TI  - Flavonoids as Putative Inducers of the Transcription Factors Nrf2, FoxO, and
      PPARgamma.
AB  - Dietary flavonoids have been shown to extend the lifespan of some model organisms
      and may delay the onset of chronic ageing-related diseases. Mechanistically, the
      effects could be explained by the compounds scavenging free radicals or
      modulating signalling pathways. Transcription factors Nrf2, FoxO, and PPARgamma
      possibly affect ageing by regulating stress response, adipogenesis, and insulin
      sensitivity. Using Hek-293 cells transfected with luciferase reporter constructs,
      we tested the potency of flavonoids from different subclasses (flavonols,
      flavones, flavanols, and isoflavones) to activate these transcription factors.
      Under cell-free conditions (ABTS and FRAP assays), we tested their free radical
      scavenging activities and used alpha-tocopherol and ascorbic acid as positive
      controls. Most of the tested flavonoids, but not the antioxidant vitamins,
      stimulated Nrf2-, FoxO-, and PPARgamma-dependent promoter activities. Flavonoids
      activating Nrf2 also tended to induce a FoxO and PPARgamma response.
      Interestingly, activation patterns of cellular stress response by flavonoids were
      not mirrored by their activities in ABTS and FRAP assays, which depended mostly
      on hydroxylation in the flavonoid B ring and, in some cases, extended that of the
      vitamins. In conclusion, the free radical scavenging properties of flavonoids do
      not predict whether these molecules can stimulate a cellular response linked to
      activation of longevity-associated transcription factors.

PMID- 28761623
TI  - Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in
      Genetically Diabetic Mice.
AB  - Oxidative stress is widely recognized as an important factor in the delayed wound
      healing in diabetes. However, the role of mitochondrial reactive oxygen species
      in this process is unknown. It was assumed that mitochondrial reactive oxygen
      species are involved in many wound-healing processes in both diabetic humans and
      animals. We have applied the mitochondria-targeted antioxidant 10-(6'
      plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of
      mitochondrial reactive oxygen species in the wound healing of genetically
      diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic
      C57BL/KsJ-db-/db- mice was significantly enhanced after long-term (12 weeks)
      administration of SkQ1. SkQ1 accelerated wound closure and stimulated
      epithelization, granulation tissue formation, and vascularization. On the 7th day
      after wounding, SkQ1 treatment increased the number of alpha-smooth muscle actin
      positive cells (myofibroblasts), reduced the number of neutrophils, and increased
      macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change
      the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell
      migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus,
      a mitochondria-targeted antioxidant normalized both inflammatory and regenerative
      phases of wound healing in diabetic mice. Our results pointed to nearly all the
      major steps of wound healing as the target of excessive mitochondrial reactive
      oxygen species production in type II diabetes.

PMID- 28761625
TI  - Effects of Redox Modulation on Cell Proliferation, Viability, and Migration in
      Cultured Rat and Human Tendon Progenitor Cells.
AB  - Tendon healing is slow and usually results in inferior fibrotic tissue formation.
      Recently, application of tendon derived stem cells (TDSCs) improved tendon
      healing in animal studies. In a chicken model, local injection of antioxidants
      reduced tendon adhesion after tendon injury. An in vitro study demonstrated that
      supplementation of H2O2 reduced tenogenic marker expression in TDSCs. These
      findings suggested that the possibility of TDSCs is involved in tendon healing
      and the cellular activities of TDSCs might be affected by oxidative stress of the
      local environment. After tendon injury, oxidative stress is increased. Redox
      modulation might affect healing outcomes via affecting cellular activities in
      TDSCs. To study the effect of oxidative stress on TDSCs, the cellular activities
      of rat/human TDSCs were measured under different dosages of vitamin C or H2O2 in
      this study. Lower dose of vitamin C increased cell proliferation, viability and
      migration; H2O2 affected colony formation and suppressed cell migration, cell
      viability, apoptosis, and proliferation. Consistent with previous studies,
      oxidative stresses (H2O2) affect both recruitment and survival of TDSCs, while
      the antioxidant vitamin C may exert beneficial effects at low doses. In
      conclusion, redox modulation affected cellular activities of TDSCs and might be a
      potential strategy for tendon healing treatment.

PMID- 28761626
TI  - Identification of retention strategies for neurosurgeons in Iran: Results from
      expert panels.
AB  - Background: The key challenge is how to encourage and retain health professionals
      in their work location. There is a list of policy options for this purpose but
      applying an appropriate and effective set of strategies requires a country level
      research. Our study aimed to identify retention strategies for neurosurgeons and
      examine both the importance and feasibility of the identified strategies using
      expert panels' point of view. Methods: First of all, a literature review was
      conducted to identify retention strategies for physicians. Then to gain consensus
      on the strategies and determine their importance and feasibility an expert panel
      was organized and a modified Delphi process was used. Results: A total of 40
      strategies were identified by the panel classified in seven categories of income
      and economic factors, professional/job factors, clinical infrastructure,
      personal/family factors, living condition and welfare, educational factors and
      career development, governmental regulations and management policies. Conclusion:
      Based on the study results, three areas of economic incentives, personal and
      professional factors got the greatest priority in health professional planning
      for retention purposes.

PMID- 28761624
TI  - Pitaya Extracts Induce Growth Inhibition and Proapoptotic Effects on Human Cell
      Lines of Breast Cancer via Downregulation of Estrogen Receptor Gene Expression.
AB  - Breast cancer is one of the most prevalent cancers in the world and is also the
      leading cause of cancer death in women. The use of bioactive compounds of
      functional foods contributes to reduce the risk of chronic diseases, such as
      cancer and vascular disorders. In this study, we evaluated the antioxidant
      potential and the influence of pitaya extract (PE) on cell viability, colony
      formation, cell cycle, apoptosis, and expression of BRCA1, BRCA2, PRAB, and
      Eralpha in breast cancer cell lines (MCF-7 and MDA-MB-435). PE showed high
      antioxidant activity and high values of anthocyanins (74.65 +/- 2.18). We
      observed a selective decrease in cell proliferation caused by PE in MCF-7 (ER+)
      cell line. Cell cycle analysis revealed that PE induced an increase in G0/G1
      phase followed by a decrease in G2/M phase. Also, PE induced apoptosis in MCF-7
      (ER+) cell line and suppressed BRCA1, BRCA2, PRAB, and Eralpha gene expression.
      Finally, we also demonstrate that no effect was observed with MDA-MB-435 cells
      (ER-) after PE treatment. Taken together, the present study suggests that pitaya
      may have a protective effect against breast cancer.

PMID- 28761627
TI  - Acute management of stroke in Iran: Obstacles and solutions.
AB  - Background: Stroke is among the leading causes of mortality and permanent
      disability in the world. Iran is located in the stroke belt and has a high age
      adjusted stroke incidence rate. In this multistep prospective qualitative study,
      we aimed at investigating the status and challenges of stroke management in Iran
      and explore possible solutions. Methods: In the first and second phase, we
      attempted to define the status of stroke management in Iran by searching the
      relevant literature and conducting semi-structured interviews with health-care
      providers in thirteen hospitals located in seven large cities in Iran. In the
      third phase, we tried to recommend possible solutions based on international
      standards and experience, as well as interviews with stroke experts in Iran and
      the United States. Results: Little public awareness of stroke symptoms and its
      urgency, low prioritization for stroke management, and an inadequate number of
      stroke-ready hospitals are some of the major obstacles toward timely treatment of
      stroke in Iran. Every hospital in our pool except two hospitals had guideline
      based algorithms for the administration of intravenous thrombolysis. However,
      there was no single call activation system for stroke alert. Data from some of
      the centers showed that hospital arrival of stroke patients to final decision
      making took 116-160 minutes. Although there were four endovascular programs in
      our target areas, there was no center with 24-hour coverage. Conclusion: There
      are many challenges as well as potentials for improvement of stroke care in Iran.
      Improving public knowledge of stroke and establishing an organized and
      comprehensive stroke program in the hospitals will improve acute stroke
      management in Iran. The Iranian ministry of health should define and advocate the
      establishment of stroke centers, track the rate of death and disability from
      stroke, introduce pathways to improve the quality of stroke care through national
      data monitoring systems, and eliminate disparities in stroke care.

PMID- 28761628
TI  - Modified Atkins diet in adult with refractory epilepsy: A controlled randomized
      clinical trial.
AB  - Background: The usefulness of the modified Atkins diet (mAD) in refractory
      epilepsy in adults has been rarely investigated. We aimed to evaluate the
      efficacy of mAD in adult with refractory epilepsy. Methods: In a controlled
      randomized clinical trial, we enrolled 66 refractory adult epileptic cases from
      February 2010 to December 2012. The patients were randomly divided into two
      groups, case groups (22 patients) used antiepileptic drugs and mAD and control
      group (32 patients) only use antiepileptic drugs. The primary outcome was at
      least 50% decrement in seizure frequency after 2 months of therapy. Results: No
      significant difference was shown in our data between groups regarding baseline
      characteristic. The differences of mean seizure attack after 2 months (P <
      0.001). (17.6%) had > 50% seizure decrease at 1 and after 2 months and 12 (35.3%)
      had 50% decrease in seizure frequency. Furthermore, in mAD group, the mean
      urinary ketone positivity was 1.75 +/- 0.28 and increasing liver enzyme was shown
      5 cases (14.7%) in mAD group and 5 cases (15.6%) in control group (P < 0.050).
      Conclusion: The mAD may be effective as a cotherapy treatment for adults with
      refractory epilepsy and decrease 2.19 times seizure frequency in comparison with
      control groups. Trials with the more tolerant dietary regime, with larger sample
      size and longer duration, should be performed in future.

PMID- 28761629
TI  - Atherogenic indices in stroke patients: A retrospective study.
AB  - Background: Stroke makes a significant cause of morbidity and mortality
      worldwide. Although derangements in the lipid profile have been suggested as a
      risk factor for the development of stroke, various studies show inconsistent
      results on the association between lipid profile and stroke. A very few studies
      have commented on the status of lipid indices in stroke patients. Methods: After
      obtaining ethical medical records of the study populations were analyzed, and
      data collected from patients admitted to the hospital with clinically diagnosed
      stroke and control group consisted of apparently healthy volunteers selected from
      the master health checkup department. Baseline characteristics and lipid profile
      parameters and the number of days of hospital stay for stroke patients were
      collected. Lipid indices were calculated using following formulae. Atherogenic
      index of plasma (AIP) = log triglyceride/high-density lipoprotein cholesterol
      (HDLc), Castelli's Risk Index (CRI-I) = Total cholesterol/HDLc, CRI-II = Low
      density lipoprotein cholesterol/HDLc, atherogenic coefficient (AC) = (Total
      cholesterol-HDLc)/HDLc, and non-HDLc (NHC) = Total cholesterol-HDL. Results: The
      study included 620 participants of which 290 were stroke patients and 330 healthy
      volunteers. 61% of stroke patients were hypertensives and 38% were diabetics 28%
      were both diabetic and hypertensives. In this study, the lipid parameters and the
      indices were significantly higher in stroke patients than the control group.
      Three indices, namely, CRI-I, AC, and NHC were found to be contributing to the
      risk of stroke significantly. There was no statistically significant correlation
      between the duration of hospital stay and lipid indices or individual parameters
      of lipid profile. Conclusion: In this study, the atherogenic lipid indices were
      significantly higher in stroke patients compared to controls.

PMID- 28761630
TI  - S100 B: A new concept in neurocritical care.
AB  - After brain injuries, concentrations of some brain markers such as S100B protein
      in serum and cerebrospinal fluid (CSF) are correlated with the severity and
      outcome of brain damage. To perform an updated review of S100B roles in human
      neurocritical care domain, an electronic literature search was carried among
      articles published in English prior to March 2017. They were retrieved from
      PubMed, Scopus, EMBSCO, CINAHL, ISC and the Cochrane Library using keywords
      including "brain", "neurobiochemical marker", "neurocritical care", and "S100B
      protein". The integrative review included 48 studies until March 2017. S100B
      protein can be considered as a marker for blood brain barrier damage. The marker
      has an important role in the development and recovery of normal central nervous
      system (CNS) after injury. In addition to extra cerebral sources of S100B, the
      marker is principally built in the astroglial and Schwann cells. The
      neurobiochemical marker, S100B, has a pathognomonic role in the diagnosis of a
      broad spectrum of brain damage including traumatic brain injury (TBI), brain
      tumor, and stroke. Moreover, a potential predicting role for the neurobiochemical
      marker has been presumed in the efficiency of brain damage treatment and
      prognosis. However further animal and human studies are required before
      widespread routine clinical introduction of S100 protein.

PMID- 28761631
TI  - Prevalence of familial multiple sclerosis in Iran: A systematic review and meta
      analysis.
AB  - Background: Familial history of multiple sclerosis (MS) has been considered as
      one of the etiologic factors of MS by several studies. It is valuable to combine
      the results of these studies. The aim of this study is to estimate the pooled
      prevalence of familial MS in Iran using meta-analysis. Methods: Using relevant
      keywords, national and international databanks were searched. Considering the
      significant heterogeneity between the results, random effect model was utilized
      to estimate the pooled prevalence of familial MS using Stata software. Results:
      After screening the selected articles, 15 studies with total sample size of 6248
      (from 60 to 1718) were identified eligible for final meta-analysis. Overall
      prevalence of familial MS in Iran was estimated as of 11.4% [95% confidence
      interval (CI): 8.7-14.1]. Point prevalence varied between 3.3% and 26.7%.
      Conclusion: Our study showed that the familial prevalence of MS among Iranian
      people is relatively high. More studies are warranted to investigate the effect
      of familial history as a risk factor for MS.

PMID- 28761632
TI  - The unexpected finding of a hemangioblastoma on the cerebellum of a patient
      undergoing treatment with natalizumab for multiple sclerosis.

PMID- 28761633
TI  - Oculopharyngeal muscular dystrophy misdiagnosed as myasthenia gravis: Case report
      and review of literature.

PMID- 28761635
TI  - A huge and invasive skull metastasis caused by renal cell carcinoma.

PMID- 28761634
TI  - Acute beriberi neuropathy mimicking Guillain-Barre syndrome after a strict
      vegetarian diet.

PMID- 28761636
TI  - The third Iranian and the second joint French-Iranian neuromuscular meeting.

PMID- 28761637
TI  - Evaluating validity of current criteria for judgment passing ER rotation among
      internee medical students.
AB  - BACKGROUND: Passing the emergency medicine internship is an essential process for
      all graduates of medical schools. The main purpose of this study was to evaluate
      validity of current criteria for judgment passing ER rotation among internee
      medical students. METHODS: In this cross-sectional study, a total of 200 students
      in the emergency departments (ED) of the teaching hospitals at Tehran University
      of Medical Sciences (TUMS) were included. The data were gathered using by a valid
      self-assessment questionnaire including demographic information and 12-items
      about the students' level of confidence with the skills and procedures under
      study. Statistical analyses were done using SPSS (version 22). RESULTS: 200
      medical students participated in this study. A Univariate analysis showed a
      significant correlation between successfuly completions of training in emergency
      medicine (passing emergency medicine in past rotations) with some items in self
      assessment questionnaire same as knowledge of interns in managing emergency
      situations (p = 0.009). The Spearman test demonstrated a significant correlation
      between the duration of emergency training (number of months which interns spent
      on the emergency training) with the some items in self-assessment questionnaire
      same as importance of emergency medicine training (p = 0.019). CONCLUSIONS:
      According to association between successfully completions of training in
      emergency medicine and self-assessment questionnaire, it seems current criteria
      for judgment passing emergency medicine rotation is valid as well as we
      recommended using self-assessment for evaluating validity of such testes.

PMID- 28761639
TI  - Rationale for a new registry on EVAR: The EXTREME study.
AB  - To report rationale of a physician-initiated study: Expanding Indications for
      Treatment with Standard EVAR in Patients with Challenging Anatomies, a Multi
      Centric Prospective Evaluation - EXTREME.

PMID- 28761638
TI  - Mean platelet volume and serum uric acid in neonatal sepsis: A case-control
      study.
AB  - BACKGROUND: Mean platelet volume (MPV) is a measure of platelet volume. It
      reveals the presence of inflammatory burden and disease activity in many
      diseases. Serum uric acid (SUA) is one of the most important antioxidants in
      human biological fluids and is responsible for neutralizing > 50% of the free
      radicals in the human blood. For this reason, it was thought that the antioxidant
      effects of SUA could increase the life expectancy and/or reduce the incidence of
      malignancy. OBJECTIVES: To determine the role of mean platelet volume (MPV) and
      serum uric acid (SUA) level in the diagnosis of neonatal sepsis (NS). METHODS:
      This case-control study was done on 80 newborns divided into 3 groups: group A (n
      = 22): clinical NS, group B (n = 18): Proven NS and Group C (n = 40): apparently
      healthy control. All patients in the study were subjected to adequate assessment
      of history, full clinical examination, complete blood count including MPV, C -
      reactive protein (CRP), blood culture in CRP positive cases, and SUA level at the
      time of diagnosis of sepsis. RESULTS: Septic neonates showed statistically higher
      values of MPV and statistically lower levels of SUA than the control group. The
      diagnostic cut-off values of MPV and SUA for NS were 10.2 fL, and 3.70 mg/dL,
      respectively. CONCLUSIONS: MPV could be assessed in the early diagnosis of
      neonatal sepsis while SUA level has lower sensitivity in neonatal sepsis.

PMID- 28761640
TI  - Predictive and diagnostic value of serum intestinal fatty acid binding protein in
      neonatal necrotizing enterocolitis (case series).
AB  - OBJECTIVES: In this study, we aimed to investigate the value of serum intestinal
      fatty acid binding protein (I-FABP) in early diagnosis and predicting the
      severity of Necrotizing enterocolitis (NEC). METHODS: This prospective study was
      performed on 160 preterm neonates ageing less than 35 weeks and weighting less
      than 2000 gm selected from the Neonatal Intensive Care Units (NICUs) of the
      Pediatric Department at Benha University hospital and Benha children hospital to
      evaluate which of them will develop NEC, after follow-up these neonates were
      divided into two groups: Group one compromised eighteen preterm neonates with
      symptoms and signs of NEC. Group two compromised ten preterm neonates as a
      control group. All participants were subjected to full clinical examination,
      abdominal X-ray and serum I-FABP. RESULTS: The 1st values of IFABP taken at birth
      showed that mean serum IFABP concentrations of the study group were higher than
      that of the control group. The 2nd values of serum IFABP taken at the start of
      feeding showed that mean IFABP concentrations of the study group were higher in
      comparison with IFABP at birth. In the 3rd values of serum, IFABP taken at the
      time of diagnosing NEC showed that mean serum IFABP concentrations of the study
      group were higher than the control group. In the 4th values of serum, IFABP taken
      one week after diagnosing NEC showed that the mean serum IFABP concentrations of
      the study group became significantly decreased in comparison with IFABP at the
      time of diagnosis in stage 1 and 2. CONCLUSIONS: Serial measurements of serum I
      FABP levels may be a useful marker for early diagnosis and prediction of disease
      severity in NEC.

PMID- 28761641
TI  - Attitudes of surgeons to the use of postoperative markers of the systemic
      inflammatory response following elective surgery.
AB  - BACKGROUND: Cancer is responsible for 7.6 million deaths worldwide and surgery is
      the primary modality of a curative outcome. Postoperative care is of considerable
      importance and it is against this backdrop that a questionnaire based study
      assessing the attitudes of surgeons to monitoring postoperative systemic
      inflammation was carried out. METHOD: A Web based survey including 10 questions
      on the "attitudes of surgeons to the use of postoperative markers of the systemic
      inflammatory response following elective surgery" was distributed via email. Two
      cohorts were approached to participate in the survey. Cohort 1 consisted of 1092
      surgeons on the "Association of Coloproctology of Great Britain and Ireland
      (ACPGBI)" membership list. Cohort 2 consisted of 270 surgeons who had published
      in this field in the past as identified by two recent reviews. A reminder email
      was sent out 21 days after the initial email in both cases and the survey was
      closed after 42 days in both cases. RESULT: In total 29 surgeons (2.7%) from
      cohort 1 and 40 surgeons (14.8%) from cohort 2 responded to the survey. The
      majority of responders were from Europe (77%), were colorectal specialists (64%)
      and were consultants (84%) and worked in teaching hospitals (54%) and used
      minimally invasive techniques (87%). The majority of responders measured CRP
      routinely in the post-operative period (85%) and used CRP to guide their decision
      making (91%) and believed that CRP monitoring should be incorporated into
      postoperative guidelines (81%). CONCLUSION: Although there was a limited response
      the majority of surgeons surveyed measure the systemic inflammatory response
      following elective surgery and use CRP measurements together with clinical
      findings to guide postoperative care. The present results provide a baseline
      against which future surveys can be compared.

PMID- 28761642
TI  - Frequency, characteristics and outcomes of appendicular neuroendocrine tumors: A
      cross-sectional study from an academic tertiary care hospital.
AB  - BACKGROUND: Appendicular neuroendocrine tumors (NET, Carcinoid tumors) of the
      appendix are rare and mostly diagnosed incidentally on the post-operative
      histopathological examination. NET are usually associated with good 5-year
      survival rates. We aimed to assess our experience for the diagnosis and
      management of NET over 11 years. METHOD: It is a retrospective chart review of
      all clinically suspected patients with acute appendicitis who underwent emergent
      appendectomy with intention to treat between January 2004-December 2014, and were
      clinically followed up until 2016. RESULTS: During the study period, a total of
      13641 patients underwent emergency appendectomy, of which 32 were histologically
      confirmed NET. The mean age of the NET cases was 25.3 +/- 7.9 years; 78% were
      males and all were clinically presented with acute appendicitis. The mean
      leucocyte was 15 +/- 14 * 109 per Liter, and mean tumor size was 4.86 +/- 3.18
      (ranged 1.5-13) mm. The median length of hospital stay was 4 (2-15) days. One
      patient had right hemicolectomy; diagnosed with right colonic cancer with NET
      being an incidental finding as part of histopathological assessment. Another
      patient required a second stage procedure; he was diagnosed as goblet cell
      carcinoid with positive margin. None of the patients died 30-day postoperatively
      and all of them survived on clinical follow-up that ranged between 2 and 13
      years. CONCLUSION: Carcinoid tumors of the appendix are rare and typically
      diagnosed incidentally. Detailed examination of routine appendectomy specimens is
      the key for diagnosis. Simple appendectomy suffices for tumors <2 cm for adequate
      clearance. Appendicular carcinoid tumors are associated with good long-term
      outcomes.

PMID- 28761643
TI  - A prospective randomised trial of isolated pathogens of surgical site infections
      (SSI).
AB  - BACKGROUND: Every surgical wound is colonized by bacteria, but only a small
      percentage displays symptoms of infection. The distribution of pathogens isolated
      in surgical site infections has not significantly changed over the last decades.
      Staph. Aureus, Coag(-) Staphylococci, Enterococcus spp and E. Coli are the main
      strains appearing. In addition, a continuously rising proportion of surgical site
      infections caused by resistant bacterial species (MRSA, C. Albicans) has been
      reported. METHODS: This prospective and randomized clinical study was performed
      in the 1st Surgical Clinic of Sismanoglion General Hospital of Athens, from
      February 2009 to February 2015. Patients undergoing elective surgery in the upper
      or lower digestive system were randomized to receive antimicrobial treatment as
      chemoprophylaxis. Each patient filled a special monitoring form, recording
      epidemiological data, surgery related information, surgical site infections (deep
      and superficial), as well as postoperative morbidity (urinary and respiratory
      infections included). The monitoring of patients was carried by multiple visits
      on a daily basis during their hospitalization and continued after they were
      discharged via phone to postoperative day 30. RESULTS: Our overall SSI incidence
      was 4,3% (31patients out of a whole of 715 patients). Specifically, the incidence
      of SSIs for scheduled surgery of the upper GI tract was 2,2% (11 out of 500
      patients) and for the lower GI tract was 9,3% (20 out of 215 patients). Seven
      main pathogens were isolated from patients with SSIs: Escherichia coli,
      Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Bacteroides
      fragilis, Staphylococcus aureus and Enterococcus faecalis. Their growth rates
      were respectively: S. Aureus (17,3%), E. faecalis (19,5%), P. aeruginosa (10,5%),
      B. Fragilis (13,4%) E. coli (20,4%), Enterobacter cloacae (9,1%) and K.
      Pneumoniae (9,8%). In addition, all the SSIs were found to be multimicrobial.
      Several studies have already revealed that patient characteristics and coexisting
      morbidities such as obesity, smoking, heart or renal failure, pre-existing
      localized infections and patients' age (especially if age exceeds 65) seem to be
      independent prognostic factors for surgical field infections. Additionally,
      classification of the surgical wound, surgical operation complexity, preoperative
      hospitalization, prolongation of surgical time and need for transfusions have
      been proved to differentiate the incidence of SSIs. CONCLUSIONS: In conclusion,
      surgical site infections are important complications affecting the healthcare
      services, the cost of hospitalization and the patient himself. Future thorough
      studies are expected to reveal much more data, regarding predisposing and
      precautionary patient and hospital characteristics.

PMID- 28761644
TI  - An extensive swelling in the anterior mandible - A case report.
AB  - INTRODUCTION: Glandular odontogenic cyst is a rare developmental odontogenic
      cyst, which often pose a challenge to diagnose it clinically. PRESENTATION OF A
      CASE: A 32 year old female patient was referred to the oral and maxillofacial
      surgery department with a chief complaint of a painless swelling in the anterior
      mandible, extending from mandibular left premolar to right first molar region,
      with fluctuancy and egg shell crackling at right premolar region. The associated
      teeth were firm. Radio graphically a large radiolucent lesion was seen extending
      from mandibular left premolar to right first molar region. DISCUSSION: We had
      many differential diagnoses including keratocystic odontogenic tumour,
      ameloblastoma and radicular cyst. Incisional biopsy was taken from the most
      fluctuant area, which was histopathologically suggestive of glandular odontogenic
      cyst. Enucleation of the cyst, peripheral ostectomy, extraction of teeth and
      Carnoy's solution application were done under general anaesthesia. CONCLUSION: We
      often neglect to include uncommon lesions in the differential diagnosis, which
      may lead to inadequacy in the management protocol. Whenever possible, incisional
      biopsy should be performed to confirm the lesion before surgical enucleation.
      Here we present a case in which we were fortunate enough to diagnose the lesion
      by an incisional biopsy and managed according to the standard protocol.

PMID- 28761645
TI  - Is glycemia control in Canadians with diabetes individualized? A cross-sectional
      observational study.
AB  - OBJECTIVE: Diabetes guidelines recommend individualized glycemic targets: tighter
      control in younger, healthier patients and consideration of more moderate control
      in the elderly and those with coexisting illnesses. Our objective was to examine
      whether glycemic control varied by age and comorbidities in Canadian primary
      care. RESEARCH DESIGN AND METHODS: Cross-sectional study using data from the
      electronic medical records of 537 primary care providers across Canada; 30 416
      patients with diabetes, aged 40 or above, with at least one encounter and one
      hemoglobin A1c (HbA1c) measurement between 1 January 2012 and 31 December 2013.
      The outcome was the most recent HbA1c, categorized into three levels of control:
      tight (<7.0% or <53 mmol/mol), moderate (7.0%-8.5%, 53 mmol/mol-69.5 mmol/mol)
      and uncontrolled (>8.5% or >69.5 mmol/mol). We adjusted for several factors
      associated with glycemic control including treatment intensity. RESULTS: Younger
      patients (aged 40-49) were more likely to have moderate as opposed to tight
      control than the older patients (aged 80+) (OR 1.28; 95% CI 1.11 to 1.49,
      p=0.001). The youngest were also more likely to have uncontrolled as opposed to
      moderately controlled glycemia (OR 3.39; 95% CI 2.75 to 4.17, p<0.0001). Patients
      with no or only one comorbidity were more likely to have moderate as opposed to
      tight control than those with three or more comorbidities (OR 1.66;95% CI 1.46 to
      1.90, p<0.0001). CONCLUSIONS: Levels of glycemic control, given age and
      comorbidities appear to differ from guideline recommendations. Research is needed
      to understand these discrepancies and develop methods to assist providers in
      personalizing glycemic targets.

PMID- 28761646
TI  - Psychometric validation of the Hypoglycemia Fear Survey-II (HFS-II) in Singapore.
AB  - OBJECTIVE: We conducted a cross-sectional study to adapt and validate the
      Hypoglycemia Fear Survey-II (HFS-II) for use in Singapore among persons with type
      1 and 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: A total of 144 patients
      with type 1 or 2 diabetes on insulin therapy for at least a year completed the
      HFS-II between September and December 2013 in the Diabetes Center at Singapore
      General Hospital. We examined the validity (content, concurrent and discriminant
      validity, and construct validity) and reliability (internal consistency and test
      retest reliability) of the instrument. Content validity was established using
      cognitive interviews. Construct validity was assessed using confirmatory factor
      analysis (CFA) followed by exploratory factor analysis (EFA) after the
      hypothesized two-factor structure was not confirmed by CFA. Measures of anxiety
      (Generalized Anxiety Disorder-7 (GAD-7)) and depression (Patient Health
      Questionnaire-9 (PHQ-9)) were used to establish concurrent validity; history of
      severe hypoglycemia and status of glycemic control were used to establish
      discriminant validity. Internal consistency was measured by Cronbach's alpha;
      test-retest reliability was measured by intracluster correlation coefficient
      (ICC). RESULTS: Scores of the adapted HFS-II had moderate positive correlations
      with measures of anxiety and depression scores (ranxiety=0.41, p<0.01;
      rdepression=0.37, p<0.01). Patients with a recent history of severe hypoglycemia
      had higher HFS-II scores than those without (mean difference=9, p<0.01). Patients
      with poor glycemic control had higher HFS-II scores than those with good control
      (p<0.05). The original two-factor structure was not confirmed in our sample. EFA
      results suggested a three-factor solution with the original Behavior subscale
      splitting into two dimensions. The adapted HFS-II displayed good internal
      consistency (Cronbach's alpha=0.93) and test-retest reliability (ICC=0.75).
      CONCLUSIONS: The adapted HFS-II has good content, concurrent and discriminant
      validity, and reliability, but its constructvalidity was not proven with the
      Behavior subscale turning out to be non-unidimensional.

PMID- 28761647
TI  - The association between diabetes mellitus and incident infections: a systematic
      review and meta-analysis of observational studies.
AB  - OBJECTIVE: To quantify the association between diabetes and the risk of incident
      infections by conducting a systematic review and meta-analysis. RESEARCH DESIGN
      AND METHODS: Two reviewers independently screened articles identified from
      PubMed, EMBASE, Cochrane Library, IPA, and Web of Science databases. Cohort
      studies (CS) or case-control studies (CCS) evaluating the incidence of infections
      in adults with diabetes were included. Infections were classified as: skin and
      soft tissue, respiratory, blood, genitourinary, head and neck, gastrointestinal,
      bone, viral, and non-specified infections. Study quality was assessed using the
      Newcastle-Ottawa Quality Assessment Scale. Summary crude and adjusted OR with 95%
      CIs were calculated using random effects models, stratified by study design.
      Heterogeneity was measured using the I2statistic and explored using subgroup
      analyses. RESULTS: A total of 345 (243 CS and 102 CCS) studies were included.
      Combining adjusted results from all CS, diabetes was associated with an increased
      incidence of skin (OR 1.94, 95% CI 1.78 to 2.12), respiratory (OR 1.35, 95% CI
      1.28 to 1.43), blood (OR 1.72, 95% CI 1.48 to 2.00), genitourinary (OR 1.61, 95%
      CI 1.42 to 1.82), head and neck (OR 1.17, 95% CI 1.13 to 1.22), gastrointestinal
      (OR 1.48, 95% CI 1.40 to 1.57), viral (OR 1.29, 95% CI 1.13 to 1.46), and non
      specified (OR 1.84, 95% CI 1.66 to 2.04) infections. A stronger association was
      observed among CCS: skin (OR 2.64, 95% CI 2.20 to 3.17), respiratory (OR 1.62,
      95% CI 1.37 to 1.92), blood (OR 2.40, 95% CI 1.68 to 3.42), genitourinary (OR
      2.59, 95% CI 1.60 to 4.17), gastrointestinal (OR 3.61, 95% CI 2.94 to 4.43), and
      non-specified (OR 3.53, 95% CI 2.62 to 4.75). CONCLUSION: Diabetes is associated
      with an increased risk of multiple types of infections. A high degree of
      heterogeneity was observed; however, subgroup analysis decreased the amount of
      heterogeneity within most groups. Results were generally consistent across types
      of infections.

PMID- 28761648
TI  - Education, immigration and income as risk factors for hemoglobin A1c >70 mmol/mol
      when diagnosed with type 2 diabetes or latent autoimmune diabetes in adult: a
      population-based cohort study.
AB  - OBJECTIVES: The aim of this research is to study education, income and
      immigration as risk factors for high hemoglobin A1c (HbA1c >70 mmol/mol (8.6%))
      when diagnosed with type 2 diabetes (T2D) or latent autoimmune diabetes in the
      adult (LADA). RESEARCH DESIGN AND METHODS: Patients were included from the All
      New Diabetics in Scania study (2008-2013). Level of education, disposable income
      and immigration year were retrieved from the longitudinal integrated database for
      labour market research (LISA) register compiled by Statistics Sweden. Logistic
      regression models were used to estimate ORs for HbA1c >70 mmol/mol (8.6%) at
      diagnosis. RESULTS: A total of 3794 patients with incident T2D (n=3 525) or LADA
      (n=269) were included. Patients with T2D with a low (<=9 years) or medium (10-12
      years) levels of education were more likely to have high HbA1c at diagnosis
      compared with patients with T2D with a high (>12 years) level of education (OR
      1.34, 95% CI 1.08 to1.66, OR 1.26, 95% CI 1.03 to 1.54). Low-income patients with
      T2D (<60% of median) were more likely to have high HbA1c at diagnosis compared
      with high-income patients withT2D (>150% of median) (OR 1.35, 95% CI 1.02 to
      1.79). CONCLUSIONS: Patients with lower levels of education or low income and are
      more likely to have HbA1c is >70 mmol/mol (8.6%) when diagnosed with T2D. An
      understanding of how socioeconomic position influences the clinical presentation
      at diagnosis may facilitate screening programs designed to target populations at
      risk for delayed diagnosis.

PMID- 28761649
TI  - Discovering successful strategies for diabetic self-management: a qualitative
      comparative study.
AB  - OBJECTIVE: This project explored lifestyles of patients in good and poor control
      to identify naturally occurring practices and strategies that result in
      successful diabetes management. RESEARCH DESIGN AND METHODS: Semistructured
      interviews with adult patients with type 2 diabetes explored diet, food
      preparation, physical activity, medication use and glucose monitoring. Patients
      (n=56) were classified into good (A1C <7.0%), fair (7.0%<A1C<8.0%) or poor (A1C
      >8.0%) control groups and matched across groups on diabetes duration (+/-5 years)
      and medication modality (none, oral, insulin+/-oral) to control for non-lifestyle
      factors. A qualitative comparative analysis identified practices that
      distinguished glycemic groups. RESULTS: Good control patients were more likely to
      test their glucose two or more times a day and reduce their sodium intake, as
      well as increase fruits and vegetables and limit portion sizes, some attaining
      good control without exercise. Fair control patients discussed several dietary
      strategies including limiting sweets, drinking non-caloric beverages, reducing
      carbs, 'cheating' (eating only a few sweets/limiting carbs in one meal to have
      more in another meal) and tested their glucose once a day. Poor control patients
      were more likely to skip antidiabetic medications and not test their glucose.
      CONCLUSIONS: Although clinical trials indicate most self-management practices
      have limited effectiveness over time, increased glucose monitoring is a valuable
      component in daily management. Research is needed on effectiveness of dietary
      strategies that emphasize sodium monitoring and allow some degree of cheating.
      Reoffering diabetes education classes and providing pill boxes as memory aids may
      help improve poor control.

PMID- 28761650
TI  - Pioglitazone and risk of mortality in patients with type 2 diabetes: results from
      a European multidatabase cohort study.
AB  - OBJECTIVES: Estimate and compare the risk of mortality in patients whose
      antidiabetic therapy is modified to include pioglitazone compared with an
      alternative antidiabetic medication at the same stage of disease progression.
      DESIGN: Retrospective cohort study. SETTING: Pooled analysis of clinical data
      collected from primary and/or secondary care settings in four European countries:
      Finland, The Netherlands, Sweden and the UK . PARTICIPANTS: 56 337 patients with
      type 2 diabetes mellitus first prescribed pioglitazone between 2000 and 2011, and
      56 337 patients never prescribed pioglitazone matched by treatment stage, history
      of diabetes, diabetes complications and cardiovascular disease, and year of
      cohort entry using exact and propensity score matching. Patients were followed-up
      for a mean of 2.90 (SD 2.21) and 2.83 (SD 2.37) years in the pioglitazone-exposed
      and non-pioglitazone-exposed groups, respectively. OUTCOMES: All-cause mortality
      ascertained from clinical or registry data. Mortality was a planned secondary
      outcome in a study primarily studying the association of pioglitazone use with
      bladder cancer risk. RESULTS: The crude overall mortality rate per 10 000 patient
      years was 206 (95% CI 199 to 213) in the pioglitazone-exposed group and 448 (95%
      CI 438 to 458) in the non-pioglitazone-exposed group. The crude HR comparing
      pioglitazone to alternative antidiabetic exposure was 0.46 (95% CI 0.45 to 0.48).
      This reduced in magnitude to 0.67 (95% CI 0.64 to 0.70) following further
      adjustment for matching variables, propensity scores, age, gender and time
      dependent variables representing use of alternative antidiabetic drugs.
      CONCLUSIONS: In this large observational cohort study of patients with type 2
      diabetes, pioglitazone exposure was associated with a statistically significant
      decrease in the risk of all-cause mortality across four European countries.
      Results should be interpreted with caution due to the potential for residual
      confounding. PROTOCOL REGISTRATION: European Network of Centres for
      Pharmacoepidemiology and Pharmacovigilance.

PMID- 28761651
TI  - Type 2 diabetes patient's perspective on Ramadan fasting: a qualitative study.
AB  - OBJECTIVE: We evaluated the beliefs, experience and diabetes management
      strategies of type 2 diabetes mellitus (T2DM) Muslim patients that chose to fast
      during Ramadan. RESEARCH DESIGN AND METHODS: A semistructured focus group
      interview was conducted with 53 participants with T2DM. Participants were
      purposefully sampled and asked to share their perspective on Ramadan fasting. All
      interviews were audio recorded, transcribed verbatim and analyzed thematically.
      RESULTS: Participants reported optimism towards fasting during Ramadan, as they
      believed that fasting was beneficial to their overall well-being, and a time for
      family bonding. Most participants made limited attempts to discuss with their
      doctors on the decision to fast and self-adjusted their medication based on
      experience and symptoms during this period. They also reported difficulty in
      managing their diet, due to fear of hypoglycemia and the collective social aspect
      of fasting. CONCLUSION: Muslims are optimistic about their well-being when
      fasting during Ramadan. Many choose to fulfill their religious obligation despite
      being discouraged by their doctors. Collaboration with religious authorities
      should be explored to ensure patients receive adequate education before fasting
      during Ramadan. TRIAL REGISTRATION NUMBER: NCT02189135; Results.

PMID- 28761652
TI  - Incidence of severe hypoglycemia in children with type 1 diabetes in the Nordic
      countries in the period 2008-2012: association with hemoglobin A 1c and treatment
      modality.
AB  - OBJECTIVE: Treatment of type 1 diabetes has been intensified aiming at
      normalizing blood glucose, which may increase the risk of severe hypoglycemia
      (SH). We aimed to compare the incidence of SH events in the four Nordic countries
      Denmark, Iceland, Norway and Sweden, and to assess the influence of hemoglobin
      A1c (HbA1c) and treatment modalities on the frequency of SH; particularly, to
      explore if a HbA1c target <=6.7% (50 mmol/mol) is feasible. RESEARCH DESIGN AND
      METHODS: Data on children below 15 years with a diabetes duration more than 1
      year, registered in the national childhood diabetes databases in the four Nordic
      countries from 2008 to 2012, were compiled. Data completeness was more than 95%.
      RESULTS: Totally 8806 (48% females) patients with 29 715 person years were
      included, mean age and diabetes duration were 11 years and 5.1 years,
      respectively. The overall rate of SH was 6.0 per 100 patient-years, and did not
      change during the study period. The Swedish population constantly had the lowest
      SH incidence while it decreased significantly in the Danish population. HbA1c
      decreased significantly over time (p<0.01), while the number of pump users
      increased (p<0.01). Stratifying for HbA1c levels showed the lowest risk of SH in
      patients with HbA1c <=6.7% (<=50 mmol/mol), but in the statistical models
      adjusting for possible confounders the difference between the HbA1c groups
      disappeared. Pump users had the lowest SH risk, also after adjusting for possible
      confounders. CONCLUSIONS: Risk of SH differs between the Nordic countries with
      the lowest risk in Sweden. Pump therapy was associated with decreased risk of SH.
      The low HbA1c group had the same or a lower risk of SH compared with the highest
      HbA1c groups. A target HbA1c <=6.7% (<=50 mmol/mol) seems achievable without
      increasing the risk of SH.

PMID- 28761654
TI  - Treatment patterns and clinical characteristics of patients with type 2 diabetes
      mellitus according to body mass index: findings from an electronic medical
      records database.
AB  - OBJECTIVE: This study evaluated relationships between glycaemic control, body
      mass index (BMI), comorbidities and pharmacological treatment in patients with
      type 2 diabetes mellitus (T2D). RESEARCH DESIGN AND METHODS: This was a
      retrospective, cross-sectional analysis of Quintiles electronic medical records
      research data (study period 1 October 2013-30 September 2014). Eligibility
      included age >=18 years, T2D diagnosis, and at least one available BMI
      measurement. RESULTS: The study included 626 386 patients (mean age, 63.8 year;
      51.3% female; 78.5% white; 62.6%, BMI >=30 kg/m2). A1c data were available for
      414 266 patients. The proportion of patients with good glycaemic control (A1c
      <=6.5) decreased as BMI category increased, ranging from 40.1% of patients with
      BMI <30% to 30.1% of patients with BMI >=40. The proportions of patients with
      poor glycaemic control (A1c >8% and A1c >=9%) increased with increasing BMI
      category. Oral antidiabetic drugs (OAD) were the most frequently used (54.4% of
      patients with A1c values). Among patients using insulin-based therapy, 50% had an
      A1c >=8% and 29% had an A1c >=9% regardless of concomitant OAD or glucagon-like
      peptide 1 receptor agonist use. Among patients using three or more OADs, 34.3%
      and 16.1% had A1c values >=8% and >=9%, respectively. There was no common trend
      observed for changes in the proportion of patients with T2D-related comorbidities
      according to BMI category. The most notable trend was a 7.6% net increase in the
      percentage of patients with hypertension from BMI <30 to BMI >=40. CONCLUSIONS:
      This large dataset provides evidence that roughly one out of four patients with
      T2D is not well controlled, and the prevalence of poor glycaemic control
      increases as BMI increases.

PMID- 28761653
TI  - Individuals with obesity and type 2 diabetes have additional immune dysfunction
      compared with obese individuals who are metabolically healthy.
AB  - OBJECTIVE: The objective of the current study was to compare the responses to
      different ex vivo immunogenic challenges between immune cells derived from
      metabolically healthy subjects with obesity and subjects with obesity and type 2
      diabetes. RESEARCH DESIGN AND METHODS: We recruited 10 metabolically healthy
      subjects with obesity (Edmonton Obesity Staging System (EOSS) stage 0) and 9
      subjects with obesity and type 2 diabetes (EOSS stage 2) aged between 21 years
      and 70 years and matched for body mass index. Peripheral blood mononuclear cells
      (PBMCs) were isolated and immune cell phenotypes and ex vivo cytokine production
      after phytohaemagglutinin (PHA, a T cell mitogen) stimulation were determined.
      Neutrophil oxidative burst activity was assessed in whole blood. RESULTS: PBMCs
      from subjects with stage 2 obesity produced significantly less interleukin (IL)
      2, IL-6 and tumour necrosis factor alpha after PHA stimulation than PBMCs from
      subjects with stage 0 obesity (all, p<0.05). Subjects with stage 2 obesity also
      had higher proportions of cytotoxic T cells, activated helper T cells
      (CD4+CD278+) and inflammatory monocytes (CD14+CRTh2+, all p<0.05).
      Poststimulation, neutrophils from subjects with stage 2 obesity produced
      significantly more free radicals, were larger and more granular and had a lower
      stimulation index (all p<0.05). CONCLUSIONS: Our results suggest that compared
      with obese individuals metabolically healthy individuals with obesity and type 2
      diabetes have an impaired neutrophil function and T cell response on challenge
      despite having a T cell population expressing more activation markers which may
      be partly responsible for the increased prevalence of infection reported in this
      population.

PMID- 28761655
TI  - Changes in risk factors and their contribution to reduction of mortality risk
      following gastric bypass surgery among obese individuals with type 2 diabetes: a
      nationwide, matched, observational cohort study.
AB  - OBJECTIVE: We recently showed that Roux-en-Y gastric bypass (RYGB) reduces risks
      of mortality, cardiovascular death and myocardial infarction in obese individuals
      compared with matched patients with diabetes mellitus (DM). We have examined
      changes in risk factors after RYGB, with the aim of explaining these effects.
      RESEARCH DESIGN AND METHODS: We matched (1:1) 6132 RYGB patients with DM reported
      to the Scandinavian Obesity Surgery Register with patients who had not undergone
      RYGB, based on sex, age, body mass index (BMI) and time, and assessed effects
      2007-2014. We used causal mediation analysis to study effects mediated through
      changes to BMI and risk factors at 1 year based on Cox proportional hazards
      models. RESULTS: Baseline BMI was 42 kg/m2. Following RYGB, the lowest BMI was
      observed after 2 years (mean 31.9 kg/m2), and hemoglobin A1c (HbA1c) after 1 year
      (mean 6.32% (45.6 mmol/mol)). Maximum high-density lipoprotein (HDL) cholesterol
      was observed after 3-5 years (mean 1.46 mmol/L). Differences in BMI, HbA1c and
      HDL between the groups were statistically significant up to 6 years, and 2-3
      years for low-density lipoprotein (LDL) and blood pressure, despite fewer glucose
      lowering, hypertensive and lipid-lowering treatments. The causal mediation
      analysis suggested that RYGB has a positive effect on mortality risk, mainly by
      means of weight reduction (as opposed to changes to the risk factors analyzed).
      CONCLUSIONS: Improvements in risk factors might contribute to the reduction of
      mortality risk after RYGB in obese individuals with type 2 diabetes, but the main
      effect seems to be mediated through a decrease in BMI, which could serve as a
      proxy for several mechanisms.

PMID- 28761656
TI  - Androstenedione and testosterone levels correlate with in vitro fertilization
      rates in insulin-resistant women.
AB  - BACKGROUND: The free androgen index (FAI) calculated using total testosterone
      measured by immunoassay does not correlate with oocyte fertilization rates;
      however, there is considerable cross-reactivity for testosterone with other
      androgens by immunoassay that is not found using isotope dilution liquid
      chromatography-tandem mass spectrometry (LC/MS/MS). AIMS: This study was done to
      determine relationship between total testosterone and androstenedione measured by
      LC/MS/MS and fertilization rates. STUDY DESIGN: 49 infertile women without
      polycystic ovary syndrome were recruited preceding an in vitro fertilization
      (IVF) cycle. Serum testosterone and androstenedione were measured by LC/MS/MS and
      correlated with IVF parameters non-insulin resistant compared with insulin
      resistant (homeostatic model assessment >2.5) women. RESULTS: For non-insulin
      resistant women, total testosterone FAI and androstenedione did not correlate
      with oocyte fertilization rates. In insulin-resistant women, there was a negative
      correlation between both testosterone and FAI and fertilization rates (r=-0.62,
      p<0.03) and r=-0.73, p=0.02, respectively). There was a positive correlation
      between androstenedione and fertilization rates (r=0.87, p<0.01). CONCLUSION: For
      insulin-resistant women, increases in testosterone and FAI were associated with
      reduced fertilization rates and androstenedione was associated with increased
      fertilization rates when measured by LC/MS/MS that should be considered to be the
      measurement method of choice.

PMID- 28761657
TI  - Improving the transition from pediatric to adult diabetes care: the pediatric
      care provider's perspective in Quebec, Canada.
AB  - OBJECTIVES: The transition from pediatric to adult care is a high-risk period for
      the emerging adult with diabetes. We aimed to determine adequacy of pediatric
      transition care structures and explore the pediatric diabetes care provider's
      perceptions of transition care. RESEARCH DESIGN AND METHODS: In-depth interviews
      with pediatric diabetes care providers from 12 diabetes centers in Quebec were
      conducted. We queried alignment with Got Transition's six core elements of
      healthcare transition, experiences, and barriers to transition care. Interview
      transcripts were reviewed for themes. RESULTS: Three centers (25%) reported
      having any elements of formal and structured transition care preparation and
      planning. When referrals were within center (n=8), pediatric providers perceived
      that transition was smoother; information sharing relied heavily on verbal
      communication rather than documented medical summaries. Barriers included lack of
      adult providers, less flexibility in adult care scheduling, patient struggles
      with multiple new adult responsibilities, and insufficient understanding by adult
      providers of these challenges. There was a perception that the quality of
      pediatric care was better than adult care. Moving out of the pediatric care
      geographical region appeared to increase risk for poor follow-up. Patient
      satisfaction and regular follow-up in adult care were thought to be good measures
      of transition success. Programs that included overlap between pediatric and adult
      care were perceived as ideal. CONCLUSIONS: Important gaps in transition care
      practices persist. Efforts should focus on improving education in transition
      practices for pediatric care providers and establishing formal transition
      policies and structures at the institutional level.

PMID- 28761658
TI  - Anagliptin ameliorates albuminuria and urinary liver-type fatty acid-binding
      protein excretion in patients with type 2 diabetes with nephropathy in a glucose
      lowering-independent manner.
AB  - OBJECTIVE: The objective of this study is to elucidate the effect of anagliptin
      on glucose/lipid metabolism and renoprotection in patients with type 2 diabetic
      nephropathy. METHODS: Twenty-five patients with type 2 diabetic nephropathy
      received anagliptin 200 mg/day for 24 weeks, and 20 patients who were switched to
      anagliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors were analyzed
      regarding primary and secondary endpoints. The primary endpoint was change in
      hemoglobin A1c (HbA1c) during treatment with anagliptin. Additionally, we
      evaluated changes in lipid data (low-density lipoprotein-cholesterol, high
      density lipoprotein-cholesterol and triglyceride), blood pressure (BP), urinary
      albumin to creatinine ratio (UACR), liver-type fatty acid-binding protein to
      creatinine ratio (ULFABP) and renal function (estimated glomerular filtration
      rate and serum cystatin C) as secondary endpoints. RESULTS: After switching to
      anagliptin from other DPP-4 inhibitors, the levels of HbA1c in the 20
      participants showed no significant change, 7.5%+/-1.2% at 24 weeks compared with
      7.3%+/-0.9% at baseline. The levels of the log10-transformed UACR were
      significantly reduced from 1.95+/-0.51 mg/g creatinine (Cr) at baseline to 1.76+/
      0.53 mg/g Cr at 24 weeks after anagliptin treatment (p<0.01). The percentage
      change in the UACR (Delta%UACR) from baseline to 24 weeks was also significantly
      lower by -10.6% (p<0.001). Lipid data, systolic BP and renal function were not
      changed during anagliptin treatment. Additionally, ULFABP in eight participants,
      who had >=5 ug/g Cr at baseline, was significantly decreased from baseline (8.5+/
      2.8 ug/g Cr) to 24 weeks (3.1+/-1.7 ug/g Cr, p<0.01) after anagliptin treatment,
      and the percentage change in the ULFABP during anagliptin treatment was -58.1%
      (p<0.001). CONCLUSIONS: Anagliptin induced no significant change in HbA1c, lipid
      data, systolic BP and renal function. However, anagliptin reduced the UACR and
      ULFABP, although without a corresponding change in HbA1c, indicating direct
      action of anagliptin on renoprotection in patients with type 2 diabetic
      nephropathy.

PMID- 28761659
TI  - The effect of free diabetes care on metabolic control and on health-related
      quality of life among youths with type 1 diabetes in Cameroon.
AB  - OBJECTIVE: To assess the effect of free diabetes care on metabolic control and on
      health-related quality of life (HRQoL) of youths living with type 1 diabetes in
      Cameroon. RESEARCH DESIGN AND METHODS: We conducted a clinical audit of a
      multicenter prospective cohort, performed in three of the nine clinics of the
      'Changing Diabetes in Children' (CDiC) project in Cameroon. We collected data on
      demography, glycemic control, diabetes acute complications, and patients' HRQoL
      at baseline and after 1 year of follow-up. RESULTS: One hundred and four patients
      (51 female) were included. The mean age was 16+/-2 years (min-max: 9-18), the
      mean duration of diabetes was 5+/-3 years, and the mean HbA1C level was 11.4%+/
      2.7%. A significant reduction in HbA1c (11.4%+/-2.7% vs 8.7+/-2.4%), episodes of
      severe hypoglycemia (27/104 vs 15/104), and episodes of ketoacidosis (31/104 vs
      7/104) were observed after 1 year (p<0.05). We did not observe any significant
      difference in the total HRQoL score (p=0.66). However, we observed a significant
      decrease in diabetes-associated symptoms (p<0.05). Age, level of education,
      duration of diabetes, glycemic control, and the presence or absence of diabetes
      complications did not significantly affect the total HRQoL score. CONCLUSIONS:
      One year after free diabetes care offered through the CDiC project, a significant
      improvement was observed in glycemic control and acute complications of diabetes,
      but not in the total score of HRQoL of youths living with type 1 diabetes
      enrolled in the project.

PMID- 28761660
TI  - Association of the DASH dietary pattern with insulin resistance and diabetes in
      US Hispanic/Latino adults: results from the Hispanic Community Health Study/Study
      of Latinos (HCHS/SOL).
AB  - OBJECTIVE: To examine the association between diet quality and both diabetes
      status and insulin resistance in Hispanic/Latino adults, and the extent to which
      differences in diet quality contribute to differences in outcomes across
      Hispanic/Latino heritage. RESEARCH DESIGN AND METHODS: Cross-sectional study.
      Data are from 15 942 individuals enrolled in the Hispanic Community Health
      Study/Study of Latinos. Diet was ascertained using two 24-hour dietary recalls,
      and diet quality was measured using the Dietary Approaches to Stop Hypertension
      (DASH) score (range: 0-80, lowest to highest). Diabetes status was defined based
      on self-reported diagnosis, use of antihyperglycemic medications, or unrecognized
      diabetes (determined by baseline laboratory measures). Insulin resistance was
      determined using homeostatic model assessment of beta-cell function and insulin
      resistance (HOMA-IR). The association between DASH and diabetes status was
      examined using multinomial logistic regression. The association between DASH and
      HOMA-IR was assessed using linear regression, and we tested whether the
      association was modified by Hispanic/Latino heritage or diabetes status. RESULTS:
      DASH score was highest in those with self-reported diabetes (controlled) and no
      medications (44.8%). A higher DASH score was associated with a lower HOMA-IR, and
      the association was the same regardless of diabetes status (p>0.8 for the
      interaction). CONCLUSIONS: The association between DASH and diabetes status was
      strongest for those with controlled self-reported diabetes and who were not
      taking antihyperglycemic medications. A higher DASH score was associated with
      less insulin resistance among Hispanics/Latinos. Differences in DASH scores by
      Hispanic/Latino heritage did not explain the differences in prevalence of
      diabetes and insulin resistance reported in the diverse Hispanic/Latino
      population. CLINICAL TRIAL NUMBER: NCT02060344.

PMID- 28761661
TI  - Association of diabetic retinopathy with both sarcopenia and muscle quality in
      patients with type 2 diabetes: a cross-sectional study.
AB  - OBJECTIVE: To examine whether the existence and severity of diabetic retinopathy
      (DR) could be associated with the prevalent sarcopenia and muscle quality in
      patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This is a cross
      sectional study of 316 patients with type 2 diabetes (mean age 65+/-12 years; 38%
      female). Body compositions were measured by the dual-energy X-ray absorptiometry.
      Patients were divided into three groups: patients without DR (NDR), with non
      proliferative DR (NPDR) and proliferative DR (PDR). Sarcopenia was diagnosed
      according to the criteria for Asians, using both skeletal muscle index (SMI) and
      grip strength (kg). Muscle quality was also determined by the grip strength
      divided by SMI. Logistic regression analyses were carried out to assess the cross
      sectional association of the severity of DR with sarcopenia. In addition, linear
      regression analyses were performed to determine the associations between DR and
      muscle quality. Selection of covariates in the multivariate logistic and linear
      regression analyses was done by a stepwise procedure. RESULTS: Among the patients
      examined, NDR, NPDR and PDR were diagnosed in 261, 38 and 17 patients,
      respectively. The prevalence of sarcopenia significantly increased along with the
      progression of DR. Multivariate logistic regression analysis showed that PDR is
      significantly associated with sarcopenia (OR 7.78, 95% CI 1.52 to 39.81, p=0.014)
      and low muscle strength (OR 6.25, 95% CI 1.15 to 33.96, p=0.034). Multivariate
      linear regression analysis additionally showed that the existence of DR was
      significantly associated with the muscle quality (standardized beta -0.136,
      p=0.005 for NPDR, standardized beta -0.146, p=0.003 for PDR). CONCLUSIONS: This
      study provides evidence that PDR is significantly associated with sarcopenia, and
      the existence of DR increases the risk for low muscle quality in patients with
      type 2 diabetes.

PMID- 28761662
TI  - Which foods are displaced in the diets of adults with type 2 diabetes with the
      inclusion of eggs in their diets? A randomized, controlled, crossover trial.
AB  - BACKGROUND: The inclusion or exclusion of specific foods from the overall diet
      inevitably affects other food choices, and this matter is routinely neglected in
      dietary guidance and nutritional epidemiology. We examined how the inclusion of
      eggs in the diets of type 2 diabetics affected dietary pattern. METHODS:
      Randomized, controlled, single-blind, crossover trial of 34 adults (mean age 64.5
      years; 14 women, 20 men) with type 2 diabetes assigned to one of two possible
      sequence permutations of two different 12-week treatments (two eggs/day or egg
      exclusion), with 6-week washout periods. For the egg inclusion phase,
      participants received advice from a dietitian on how to preserve an isocaloric
      condition relative to the egg exclusion phase. To assess changes in dietary
      pattern in the diets of our study participants, we analyzed the 12 components of
      the 2010 Healthy Eating Index. RESULTS: The inclusion of eggs was associated with
      reduced consumption of refined grains nearing statistical significance (-0.7+/
      3.4 vs 0.7+/-2.2; p=0.0530). The consumption of total protein foods significantly
      increased from baseline (0.3+/-0.7; p=0.0153) with the inclusion of eggs for 12
      weeks, while the consumption of dairy products significantly decreased with the
      exclusion of eggs from their diets (-1.3+/-2.9; p=0.0188). CONCLUSIONS: Eggs in
      the diets of type 2 diabetics may lead to increased consumption of some healthful
      foods and reduced consumption of some less healthful foods. TRIAL REGISTRATION
      NUMBER: NCT02052037; Post-results.

PMID- 28761663
TI  - Standardized screening for periodontitis as an integral part of multidisciplinary
      management of adults with type 2 diabetes: an observational cross-sectional study
      of cohorts in the USA and UK.
AB  - OBJECTIVE: To determine prevalence and factors predictive of periodontitis by
      using a standardized assessment model in adults with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: We performed an observational cross-sectional study to
      determine the burden of periodontitis in adults with type 2 diabetes attending
      urban, ambulatory referral centers in the USA and UK. Full-mouth probing was
      performed and periodontitis was diagnosed based on either a low (>=5 mm at >=1
      site) or high pocket probing-depth threshold (>=6 mm at >=1 site). Results were
      stratified into a five-stage schema and integrated with other clinical variables
      into the novel Diabetes Cross-Disciplinary Index to function as a balanced health
      scorecard. Corresponding demographic and routinely collected health data were
      obtained and comparisons were made between patients with and without
      periodontitis. Multivariable logistic regression was performed to identify
      factors predictive of the presence or absence of periodontitis. RESULTS: Between
      our two cohorts, 253 patients were screened. Caucasians comprised >90% and
      Hispanic Americans >75% of the UK and US cohorts, respectively. Males and females
      were equally distributed; mean age was 53.6+/-11 years; and 17 (6.7%) were
      edentulous. Of the 236 dentate patients, 128 (54.2%) had periodontitis by low
      threshold and 57 (24.2%) by high threshold. Just 17 (7.2%) were periodontally
      healthy. No significant differences in age, HbA1c, blood pressure, body mass
      index, low-density lipoprotein cholesterol, or smoking status (all p>0.05) were
      identified between those with or without periodontitis (regardless of threshold)
      and none was found to be a significant predictor of disease. CONCLUSIONS:
      Periodontitis is frequent in adults with type 2 diabetes and all should be
      screened. Periodontal health status can be visualized with other comorbidities
      and complications using a novel balanced scorecard that could facilitate patient
      clinician communication, shared decision-making, and prioritization of individual
      healthcare needs.

PMID- 28761664
TI  - Glucose-lowering effect of whey protein depends upon clinical characteristics of
      patients with type 2 diabetes.
AB  - OBJECTIVE: Whey protein (WP) intake has been shown to reduce postprandial
      glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute
      challenge or weight loss studies. It is not known if WP supplementation can
      provide sustained glucose lowering. Our goal was to investigate the effects of WP
      on glycemia comprehensively by using continuous glucose monitoring (CGM) while
      avoiding the confounding effects of variable food intake through controlled
      feeding. RESEARCH DESIGN AND METHODS: This double-blinded and placebo (PL)
      controlled study included 22 patients with T2DM patients (11 male, 11 female; age
      57.1+/-12.6 years) on diet or metformin monotherapy. First, one serving (21 g) of
      WP was compared with PL in parallel-armed acute challenge studies. Next, in a
      crossover design, each patient underwent CGM twice, over 2 consecutive weeks, 3.5
      days each week. Identical diets were provided by the study during both CGM
      periods. During the first CGM, one serving of either WP or PL was consumed before
      breakfast and another before dinner. During the second CGM, participants switched
      to the alternate supplement. Order of the supplements was randomized. RESULTS:
      During acute challenge studies, WP stimulated insulin and glucagon-like peptide
      (GLP)-1 secretion; suppressed ghrelin (all p<0.05), while PL had no effect.
      During CGM, glucose response to WP varied depending on the baseline
      characteristics of the patients. When evaluated using linear regression, the most
      predictive baseline variables were body mass index (BMI) (p=0.0006),
      triglycerides (p=8.3*10-5) and GLP-1 (p=0.006). Lower BMI, triglyceride and GLP-1
      predicted decreased glucose levels on WP. Obesity, hypertriglyceridemia and high
      fasting GLP-1 concentrations predicted increased glucose levels. CONCLUSIONS:
      Effects of WP supplementation on glycemia in T2DM depend on the baseline
      characteristics. Lower body weight, normal triglyceride and lower GLP-1 levels
      predict glucose lowering. In contrast, obesity, hypertriglyceridemia and high
      baseline GLP-1 predict increased glucose response.

PMID- 28761665
TI  - Efficacy of recombinant bovine epidermal growth factor in the treatment of
      experimental subclinical Staphylococcus aureus mastitis in a ewe model.
AB  - Staphylococcus aureus is the most common contagious mastitis pathogen of dairy
      cattle. Antimicrobial treatment of infected cattle results in variable cure
      rates. Epidermal growth factor (EGF) plays an important role in the modulation of
      host innate immune responses and the regulation of mammary epithelial
      regeneration, indicating that EGF may be useful as a treatment for mastitis. A
      pilot study was conducted to evaluate the efficacy of recombinant bovine EGF
      (rbEGF) for the treatment of S aureus intramammary infection (IMI) using an ovine
      model. Each ewe was experimentally infected with S aureus in both udder halves.
      One udder half of each ewe received one of two treatments: EGF (n=13) or
      pirlimycin (n=13). The contralateral udder half of each ewe received sterile
      saline as a control. The bacteriological cure rate following rbEGF was
      significantly lower (15 per cent) than that attained with pirlimycin
      hydrochloride (61 per cent) and did not differ from that following treatment with
      sterile saline. Cure rates following treatment with rbEGF were not significantly
      different to those following sterile saline. Given that EGF is associated with
      modulation of host immunity and wound healing, future studies into EGF should not
      focus on whether EGF increases cure rates of S aureus IMI.

PMID- 28761666
TI  - Radial and ulnar fracture treatment with paraosseous clamp-cerclage stabilisation
      technique in 17 toy breed dogs.
AB  - OBJECTIVE: Description of surgical technique, complications and outcome of
      radius/ulna fractures in toy and miniature breed dogs treated with the
      paraosseous clamp-cerclage stabilisation (PCCS) method. STUDY DESIGN:
      Retrospective study. METHODS: Clinical records of small breed dogs with fractures
      of the radius and ulna were reviewed between January 2011 and January 2016.
      Inclusion criteria were bodyweight of <=3.5 kg, fracture of the radius and ulna
      of one or two limbs without previous repair attempts, available follow-up
      information, and the use of PCCS for repair of the fracture as the sole method of
      fixation. RESULTS: Seventeen fractures in 17 dogs were included in the study.
      Radiographic union was documented in 13/17 cases. Median time to radiographic
      union was 13 weeks (range: 5-53 weeks). Major complications occurred in 24 per
      cent (4/17) due to implant failure, and for revision surgery the PCCS method was
      chosen in all four cases. Three of four revised fractures healed
      radiographically. One of the four dogs was lost for radiographic follow-up, but
      the owner could be contacted for a telephone questionnaire. Eleven of 17 dogs
      achieved an excellent return to function without any lameness during clinical
      examination, but 5/17 dogs showed an intermittent mild lameness despite full
      radiographic union. Routine implant removal was performed in 9/17 dogs. The
      owners of 15/17 dogs could be contacted for a telephone questionnaire for a long
      term follow-up. No further complications were reported. CONCLUSIONS: PCCS is a
      feasible low-cost internal fixation technique for repairing radial and ulnar
      fractures in toy breed dogs. Further biomechanical and clinical studies are
      needed for better evaluation of the PCCS method.

PMID- 28761667
TI  - Correlation between capillary oxygen saturation and small intestinal wall
      thickness in the equine colic patient.
AB  - The surgical evaluation of haemorrhagic infarcted intestine and the decision for
      or against bowel resection require a lot of experience and are subjective. The
      aim of this prospective, clinical study was to examine the correlation between
      oxygen saturation and small intestinal wall (IW) thickness, using two objective
      methods. In 22 colicky horses, the blood flow, oxygen saturation and relative
      amount of haemoglobin were measured intraoperatively via laser Doppler and white
      light spectroscopy (O2C, oxygen to see, LEA Medizintechnik) at six measuring
      points (MPs) in small and large intestines. Furthermore, the IW thickness was
      measured ultrasonographically. Nine of 22 horses had an increased small IW
      thickness greater than 4 mm (Freeman 2002, Scharner and others 2002, le Jeune and
      Whitcomb 2014) at measuring point 1 (MP1) (strangulated segment), four horses had
      a thickened bowel wall at measuring point 3 (MP3) (poststenotic) and one at
      measuring point 2 (MP2). The oxygen saturation was 0 at MP1 in six horses, at MP3
      in two horses and at MP2 (prestenotic) in one. Oxygen saturation and small IW
      thickness were independent of each other at MP1 and MP2. At MP3, the two
      parameters were negatively correlated. In summary, it is not possible to draw
      conclusions about oxygen saturation based on IW thickness.

PMID- 28761668
TI  - Characterisation of InlA truncation in Listeria monocytogenes isolates from farm
      animals and human cases in the province of Quebec.
AB  - The introduction of Listeria monocytogenes into the food production chain is a
      concern, with numerous grouped cases of listeriosis associated with milk-derived
      or pork-derived products have been documented. Management of this zoonotic
      pathogen considers all strains as an equal risk. Recently, a new perspective for
      characterisation of strain virulence was introduced with the discovery of the
      unaltered sequence of InlA as a determinant of strain virulence; this has also
      been reported as an infrequent finding among so-called environmental strains,
      that is, strains isolated from food or from surfaces in food industries. The aim
      of this study was to differentiate L monocytogenes strains isolated from animal
      cases versus those from human cases and to differentiate clinical strains from
      environmental ones using a Caenorhabditis elegans virulence testing model. In
      Quebec in 2013/2014, the surveillance of L monocytogenes clinical isolates
      registered a total of 20 strains of animal origin and 16 pulsed-field gel
      electrophoresis types isolated from human cases. The mixed PCR multiplex
      agglutination protocol used for geno-serotyping clearly discriminated genogroup
      IVB strains from bovine and human origins. The presence of a premature stop codon
      single nucleotide polymorphism in the inlA gene sequence in clinical strains and
      the identical behaviour of particular strains in the C elegans model are
      discussed in this paper from the perspective of industrial management of L
      monocytogenes risk.

PMID- 28761669
TI  - Prevalence of individual and bulk tank milk antibodies of bovine herpesvirus type
      1 and its relation to milk quality parameters on dairy farms in Catalonia (north
      east Spain).
AB  - Bovine herpesvirus type 1 (BoHV-1) is the causative agent for infectious bovine
      rhinotracheitis and infectious pustular vulvovaginitis in cows or balanoposthitis
      in bulls. In this study, individual and bulk tank milk (BTM) samples from 5
      Catalan dairy farms with different control strategies against BoHV-1 were
      analysed during the course of a year for milk quality parameters and glycoprotein
      E (gE) antibodies. Detection of gE antibodies was carried out with ELISA
      techniques. Prevalence of BoHV-1 varied between farms, and was stable during the
      study in individual and BTM samples. Comparing the antibody results of samples
      with milk quality parameters, positive samples with higher levels of antibodies
      corresponded to lower lactose and to higher percentages of fat and somatic cells.

PMID- 28761670
TI  - Potential contribution of lifestyle and socioeconomic factors to healthy user
      bias in antihypertensives and lipid-lowering drugs.
AB  - OBJECTIVES: Healthy user bias arises when users of preventive medications such as
      lipid-lowering drugs (LLDs), hormone replacement therapy and antihypertensive
      (AH) medications are healthier than non-users due to factors other than
      medication effects, making the medications appear more beneficial in
      observational studies of effectiveness and safety. The purpose of the study is to
      examine factors contributing to healthy user effect in patients taking AHs or
      LLDs. METHODS: Among patients with hypertension or hyperlipidaemia in a
      population-based sample from the National Health and Nutrition Examination Survey
      (1999-2010), we assessed the association between socioeconomic and lifestyle
      factors and the use of AHs/LLDs by logistic regression with adjustment for
      demographics and comorbidities in a cross-sectional study. RESULTS: When 9715
      AH/LLD users were compared with 3725 non-users, AH/LLD users were more likely to
      be: highly educated (OR 1.2, 95% CI 1.2 to 1.3), non-impoverished (OR 1.3, 95% CI
      1.2 to 1.4), current non-smokers (OR 1.2, 95% CI 1.1 to 1.4), physically active
      (OR 1.1, 95% CI 1.0 to 1.2) and consume more calcium (OR 1.1, 95% CI 1.0 to 1.3)
      but less likely to have normal body mass index (OR 0.6, 95% CI 0.6 to 0.7) or to
      meet dietary sodium recommendations (OR 0.8, 95% CI 0.7 to 0.9). CONCLUSIONS: We
      identified several salutary lifestyle factors associated with AH/LLD use in a
      representative US population. Healthy user effect may be partly explained by
      better socioeconomic profiles and lifestyles in AH/LLD users compared with non
      users.

PMID- 28761672
TI  - Adjunctive interpulmonary isthmus ablation has no added effects on atrial
      fibrillation recurrence.
AB  - OBJECTIVE: Data on the efficacy of adjunctive interpulmonary isthmus ablation
      following completion of extensive encircling pulmonary vein isolation (EEPVI) on
      atrial fibrillation (AF) recurrence have still been insufficient. We aimed to
      compare the AF recurrence between EEPVI with and without adjunctive
      interpulmonary isthmus ablation. METHODS: We enrolled 200 consecutive patients
      with paroxysmal AF (first session) who underwent EEPVI with double-Lasso
      technique. Patients were prospectively randomised into two groups: EEPVI with
      (group 1) and without (group 2) adjunctive interpulmonary isthmus ablation.
      RESULTS: No differences were found in patients' clinical and echocardiographic
      backgrounds, including arrhythmia status, between the two groups. No differences
      were also observed in complications (two groin haematoma in both groups). All
      patients in both groups reached the EEPVI endpoint. The AF recurrence rate
      between groups 1 (32/100, 32%) and 2 (33/100, 33%; p=1.0) was quite similar
      during the follow-up period (45+/-5 months; 36-54 months). The two groups showed
      identical Kaplan-Meier AF-free curves (p=0.460; NS). Similar pulmonary vein (PV)
      reconnection incidence was observed in both groups during the second session.
      Durable isolation between the superior and inferior PVs was confirmed in 88%
      (21/27) of patients in group 1, indicating that interpulmonary isthmus ablation
      maintained a non-conducting state in a considerable number of patients.
      Nevertheless, AF recurrence was identical between the two groups. CONCLUSION: The
      results of our study showed similar AF recurrence rates between the two groups,
      indicating that adjunctive interpulmonary isthmus ablation with EEPVI has no
      obvious effects on AF recurrence.

PMID- 28761671
TI  - Predictors and clinical implication of high-sensitivity cardiac troponin-I
      elevation following diagnostic cardiac catheterisations.
AB  - OBJECTIVES: Although diagnostic coronary angiography (CAG) is performed
      worldwide, procedure-related myocardial necrosis (PMN) following diagnostic
      catheter-based procedures has not been well investigated. The aim of this study
      was to determine clinical and procedural factors associated with PMN, using a
      high-sensitivity cardiac troponin I (hs-cTnI) assay, and to investigate the
      clinical implications of PMN. METHODS: Among 697 patients undergoing elective CAG
      and pre- and post-procedural hs-cTnI (pre-TnI, post-TnI, respectively)
      measurements, a total of 538 patients (124 female) were evaluated, with 2.2% lost
      during follow-up. Minor PMN was defined as post-TnI above the sex-specific upper
      reference limit (URL), with a 20% increase from the pre-TnI level. Major PMN was
      defined as post-TnI above 5x the URL. Clinical and procedural factors predicting
      PMN and the association between PMN and major adverse cardiac events (MACE)
      following CAG were examined. RESULTS: PMN of any type was detected in 178
      patients (33.0%), while major PMN was observed in 32 patients (5.9%). Female sex,
      estimated glomerular filtration rate, procedural time, left ventricular end
      diastolic pressure (LVEDP) and fractional flow reserve measurement independently
      predicted any PMN; whereas, only LVEDP and log-transformed N-terminal pro-brain
      natriuretic peptide independently predicted major PMN. The incidence of MACE was
      significantly associated with major PMN. Cox proportional-hazards models revealed
      that major PMN, pre-TnI, and the absence of statin use were independently
      associated with MACE. CONCLUSIONS: Diagnostic cardiac catheteriation may
      highlight cardiomyocyte susceptibility to stress in patients with or without CAD.
      CAG-related major myocardial injury might be associated with future adverse
      cardiac events independently of the presence or absence of functional stenosis.

PMID- 28761673
TI  - Evaluation of intermediate coronary stenoses in acute coronary syndromes using
      pressure guidewire.
AB  - Fractional flow reserve (FFR) is increasingly used to guide myocardial
      revascularisation. However, supporting evidence regarding its use originates from
      studies that have enrolled mainly patients with stable angina, while patients
      with acute coronary syndromes (ACS) have not been included. Notably,
      multifactorial microvascular dysfunction and an increased sympathetic tone in
      patients with ACS may lead to blunted response to adenosine and false-negative
      results of FFR due to submaximal hyperaemia. This may raise the possibility of
      deferring treatment of stenosis that instead would have needed dilatation, thus
      leaving a residual risk of preventable cardiac events. In this literature review,
      we aim at summarising laboratory and clinical investigations concerning the use
      of FFR in culprit and non-culprit lesions in ACS. Furthermore, we will report
      recent data on instantaneous wave-free ratio, an adenosine-free index of
      functional stenosis severity, in stable coronary artery disease and in patients
      with ACS.

PMID- 28761674
TI  - Risk factors for worsening renal function and their association with long-term
      mortality following transcatheter aortic valve implantation: data from the
      SWEDEHEART registry.
AB  - BACKGROUND: The occurrence of persistent acute kidney injury (pAKI) following
      transcatheter aortic valve implantation (TAVI) has serious implications. METHODS:
      There were 1540 patients undergoing and surviving TAVI included in the nationwide
      SWEDEHEART registry between 2008 and 2015. Creatinine was measured at baseline
      and discharge, and those with baseline estimated glomerular filtration rate
      (eGFR) <15 mL/min/1.73 m2 or dialysis were excluded. pAKI was defined by and
      encompassing theValve Academic Research Consortium-2 (VARC-2) criteria: increase
      in serum creatinine concentration >=26.5 MUmol/L or increase by >=50% (1.5*), or
      start of in-hospital dialysis until hospital discharge. Logistic regression
      analysis was used to find baseline factors associated with pAKI. Adjusted Cox
      regression analysis was used to assess the association of pAKI with mortality.
      Median follow-up was 1.8 years (IQR 0.7-3.0). RESULTS: pAKI occurred in 6.1%
      (n=94) of the patients (71.3% male). These patients had higher creatinine level
      (117+/-50 vs 100+/-35 mmol/L, p<0.001), but similar baseline eGFR (59+/-21 vs
      56+/-23 mL/min/1.73 m2, p=0.18) and received higher contrast volume (129 mL +/-89
      vs 110 mL +/-78, p=0.027). On multivariable logistic regression analysis, pAKI
      was predicted by eGFR (OR 0.88, 95% CI (0.79 to 0.98), p=0.019), male gender (OR
      2.68, 95% CI (1.63 to 4.38), p<0.001) and apical access (OR 2.23, 95% CI (1.35 to
      3.69), p=0.002), whereas contrast volume/10 mL (OR 1.02, 95% CI (1.00 to 1.05),
      p=0.052) did not reach statistical significance. Mortality at 1 year/end of
      follow-up was 10.4%/26.9%. pAKI was associated with a doubled risk of death (HR
      2.04, 95% CI (1.49 to 2.81), p<0.001). CONCLUSION: Persistent AKI after TAVI
      occurs in 6.1% and is associated with a doubled long-term mortality. Special
      efforts to avoid AKI should be taken, especially among vulnerable patients.

PMID- 28761675
TI  - Time-based measures of treatment effect: reassessment of ticagrelor and
      clopidogrel from the PLATO trial.
AB  - OBJECTIVE: Treatment effects to binary endpoints using time-to-event data in
      randomised controlled trials are typically summarised by reporting HRs derived
      with Cox proportional hazard models. Alternative and complementary methods
      include summarising the between-treatment differences on the metric time scale,
      quantifying the effect as delay of the event (DoE). The aim of this study was to
      reassess data from the PLATO study expressing the effects as the time by which
      the main outcomes are delayed or hastened due to treatment. METHODS: PLATO was a
      randomised controlled double-blind multicentre study (n=18,624), conducted
      between 2006 and 2008, which demonstrated superiority of the antiplatelet
      treatment ticagrelor over clopidogrel in reducing risk of several cardiovascular
      events. In the present study, four of the main PLATO outcomes were reassessed by
      calculating the time by which an event may be delayed due to the treatment.
      RESULTS: The effects of ticagrelor, as compared with clopidogrel, consisted of a
      substantial delay of the evaluated outcomes, ranging from 83 to 98 days over 400
      day follow-up. The Delay of Events Curves showed that the effects progressively
      increased over time, and the significant findings were concordant with those
      presented in the original PLATO study. CONCLUSIONS: This study confirmed evidence
      of a beneficial effect of ticagrelor over clopidogrel, and provided the magnitude
      of such effects in terms of delayed event time. Investigating time-to-event data
      with a percentile approach allows presenting treatment effects from randomised
      controlled studies as absolute measures of the time by which an event may be
      delayed due to the treatment. TRIAL REGISTRATION NUMBER: PLATO
      (www.clinicaltrials.gov; NCT00391872); Results.

PMID- 28761676
TI  - Characterisation of clot microstructure properties in stable coronary artery
      disease.
AB  - BACKGROUND: Coronary artery disease (CAD) is associated with an increased
      prothrombotic tendency and is also linked to unfavourably altered clot
      microstructure. We have previously described a biomarker of clot microstructure
      (df) that is unfavourably altered in acute myocardial infarction. The df
      biomarker assesses whether the blood will form denser or looser microstructures
      when it clots. In this study we assessed in patients with stable chest pain
      whether df can differentiate between obstructed and unobstructed CAD. METHODS: A
      blood sample prior to angiography was obtained from 251 consecutive patients
      undergoing diagnostic coronary angiography. Patients were categorised based on
      angiographic findings as presence or absence of obstructive CAD (stenosis >=50%).
      The blood sample was assessed using the df biomarker, standard laboratory markers
      and platelet aggregometry (Multiplate). RESULTS: A significant difference
      (p=0.028) in df was observed between obstructive CAD (1.748+/-0.057, n=83) and
      unobstructive CAD (1.732+/-0.052, n=168), where patients with significant CAD
      produce denser, more tightly packed clots. df was also raised in men with
      obstructive CAD compared with women (1.745+/-0.055 vs 1.723+/-0.052, p=0.007).
      Additionally df significantly correlated with the platelets response to
      arachidonic acid as measured by the ASPItest area under the curve readings from
      platelet aggregometry (correlation coefficient=0.166, p=0.008), a low value of
      the ASPItest indicating effective aspirin use was associated with looser, less
      dense clots. CONCLUSIONS: For the first time, we characterise clot
      microstructure, as measured by df, in patients with stable CAD. df can
      potentially be used to risk-stratify patients with stable CAD and assess the
      efficacy of therapeutic interventions by measuring changes in clot
      microstructure.

PMID- 28761677
TI  - Comparison of the Chronic Kidney Disease Epidemiology Collaboration, the
      Modification of Diet in Renal Disease study and the Cockcroft-Gault equation in
      patients with heart failure.
AB  - BACKGROUND: It is unknown how the creatinine-based renal function estimations
      differ for dose adjustment cut-offs and risk prediction in patients with heart
      failure. METHOD AND RESULTS: The renal function was similar with the Chronic
      Kidney Disease Epidemiology Collaboration (CKD-EPI) (median 59 mL/min/1.73 m2,
      IQR 42 to 77) and Modification of Diet in Renal Disease Study (MDRD) (59
      mL/min/1.73 m2, IQR 43 to 75) and slightly lower with the Cockcroft-Gault (CG)
      equation (57 mL/min, IQR 39 to 82). Across the commonly used renal function
      stages, the CKD-EPI and the MDRD classified patients into the same stage in 87.2%
      (kappa coefficient 0.83, p<0.001); the CKD-EPI and the CG equation agreed in
      52.3% (kappa coefficient 0.39, p<0.001). Hence, a differing number of patients
      will receive dose adjustment depending on which formula is used as cut-off. The
      CG equation predicted worse prognosis better (c-statistics 0.740, 95% CI 0.734 to
      0.746) than CKD-EPI (0.697, 95% CI 0.690 to 0.703, p<0.001) and MDRD (0.680, 95%
      CI 0.734 to 0.746). Using net reclassification improvement (NRI), the CG
      identified 12.8% more patients at higher risk of death as compared with the CKD
      EPI equation. Patients registered in the Swedish Heart Failure Registry (n= 40
      736) with standardised creatinine values between 2000 and 2012 had their renal
      function estimated with the CKD-EPI, the MDRD and the CG. Agreement between the
      formulas was compared for categories. Prediction of death was assessed with c
      statistics and with NRI. CONCLUSION: The choice of renal function estimation
      formula has clinical implications and differing results at various cut-off
      levels. For prognosis, the CG predicts mortality better than the CKD-EPI and
      MDRD.

PMID- 28761678
TI  - Polymer-free sirolimus-eluting stents in a large-scale all-comers population.
AB  - OBJECTIVE: The objective of this study was to assess the safety and efficacy of a
      polymer-free sirolimus coated, ultrathin strut drug-eluting stent (PF-SES) in an
      unselected patient population with a focus on acute coronary syndrome (ACS).
      Furthermore, stable coronary artery disease (CAD) with short (<=6 months) versus
      long (>6 months) dual antiplatelet therapy (DAPT) were also studied. METHODS:
      Patients who received PF-SES were investigated in an unselected large-scale
      international, single-armed, multicenter, 'all comers' observational study. The
      primary endpoint was the 9-month target lesion revascularisation (TLR) rate,
      whereas secondary endpoints included the 9-month major adverse cardiac events
      (MACE) and procedural success rates. A priori defined subgroups such as patients
      with ACS, diabetes, lesion subsets and procedural characteristics relative to
      DAPT were investigated. RESULTS: A total of 2877 patients of whom 1084 had ACS
      were treated with PF-SES (1.31+/-0.75 stents per patient). At 9 months, the
      accumulated overall TLR rate was 2.3% (58/2513). There was no significant
      difference between ACS and stable CAD (2.6% vs 2.1%, p=0.389). However, the
      overall MACE rate was 4.3% (108/2513) with a higher rate in patients with ACS
      when compared with the stable CAD subgroup (6.1%, 58/947 vs 3.2%, 50/1566,
      p<0.001). CONCLUSIONS: PF-SES angioplasty is safe and effective in the daily
      clinical routine with low rates of TLR and MACE in an unselected patient
      population. Our data are in agreement with prior clinical findings that extended
      DAPT duration beyond 6 months do not improve clinical outcomes in patients with
      stable CAD (ClinicalTrials.gov Identifier NCT02629575). TRIAL REGISTRATION
      NUMBER: NCT02629575.

PMID- 28761679
TI  - The safety, efficacy and cost-effectiveness of stress echocardiography in
      patients with high pretest probability of coronary artery disease.
AB  - OBJECTIVE: In this study, we assess the clinical and cost-effectiveness of stress
      echocardiography (SE), as well as the place of SE in patients with high pretest
      probability (PTP) of coronary artery disease (CAD). METHODS: We investigated 257
      patients with no history of CAD, who underwent SE, and they had a PTP risk score
      >61% (high PTP). According to the National Institute for Health and Care
      Excellence guidance (NICE CG95, 2010), these patients should be investigated
      directly with an invasive coronary angiogram (ICA). We investigated those
      patients with SE initially and then with ICA when appropriate. Follow-up data
      with regard to Major Adverse Cardiac and Cerebrovascular Events (MACCE, defined
      as cardiovascular mortality, cerebrovascular accident (CVA), myocardial
      infarction (MI) and late revascularisation for acute coronary syndrome/unstable
      angina) were recorded for a period of 12 months following the SE. The tariff for
      SE and ICA is L300 and L1400, respectively. RESULTS: 106 patients had a positive
      SE (41.2%) and 61 of them (57.5%) had further investigation with ICA. 15 (24.6%)
      of these patients were revascularised. The average cost per patient for
      investigations was L654.09. If NICE guidance had been followed, the cost would
      have been significantly higher at L1400 (p<0.001). Overall, 5 MACCE (2.0%) were
      recorded; 4 (3.8%) in the group of positive SE (2 CVAs and 2 MIs) and 1 (0.7%) in
      the group of negative SE (1 CVA). There was no MI and no need for
      revascularisation in the negative SE group. CONCLUSION: Our approach to
      investigate patients who present with de novo chest pain and high PTP, with SE
      initially and subsequently with ICA when appropriate, reduces the cost
      significantly (L745.91 per patient) with a very low rate of MACCE. However, this
      study is underpowered to assess safety of SE.

PMID- 28761680
TI  - Nurse-coordinated care improves the achievement of LDL cholesterol targets
      through more intensive medication titration.
AB  - BACKGROUND: Nurse-coordinated care (NCC) improves the achievement of low-density
      lipoprotein-cholesterol (LDL-C) targets after an acute coronary syndrome (ACS).
      We hypothesised that NCC improves achievement of LDL-C targets through more
      intensive medication titration. METHODS: We used data from Randomised Evaluation
      of Secondary Prevention by Outpatient Nurse Specialists (RESPONSE), a multicentre
      randomised trial on the efficacy of NCC in 754 ACS patients. Follow-up data were
      collected at 6 and 12 months. To enable comparison between the various types and
      dosages of statins, we used the average lipid-lowering potency (ALLP, % LDL-C
      lowering) as an indicator of lipid-lowering medication intensity. RESULTS: Most
      patients in NCC intervention and usual care groups (96%) had started lipid
      lowering therapy during the index hospitalisation. At 6 months, titration
      activities (up or down) were applied in 45% of NCC patients compared with 24% of
      patients receiving usual care (p<0.001), and a difference was also seen at 12
      months follow-up (52% vs 34%, p<0.001). In patients not on LDL-C target at
      baseline, titration activities at 6 months were recorded in 63% and 30% of NCC
      and usual care patients respectively (p<0.001), with increased titration
      activities in both groups at 12 months (69% vs 43%, p<0.001). CONCLUSION: NCC is
      associated with more frequent and intense lipid-lowering medication titration to
      reach LDL-C targets as compared with usual care alone. Further, merely starting
      the guideline-recommended dose is insufficient to reach the guideline-recommended
      LDL-C target level. TRIAL REGISTRATION NUMBER: TC1290 (Netherlands).

PMID- 28761682
TI  - A comparative study of different imaging modalities for successful percutaneous
      left atrial appendage closure.
AB  - OBJECTIVES: Accurate sizing of the left atrial appendage (LAA) is essential when
      performing percutaneous LAA closure. This study aimed to compare different LAA
      imaging modalities and sizing methods in order to obtain successful LAA closure.
      BACKGROUND: Percutaneous LAA closure is an increasingly used treatment strategy
      to prevent stroke in patients with atrial fibrillation. LAA sizing has typically
      been done by 2D-transoesophageal echocardiography (TEE). METHODS: Patients who
      had a preprocedural TEE and preprocedural and postprocedural multislice CT (MSCT)
      were identified. Preprocedural measurements of LAA ostia and landing zones by 2D
      TEE, MSCT and angiography were collected and analysed for those patients with
      successful LAA closure - i.e. with no contrast leakage at 3-month follow-up MSCT.
      RESULTS: The study population (n=67) had a mean CHA2DS2-VASc score of 3.0 and HAS
      BLED score of 2.7. Fifty-eight patients (87%) were identified to have successful
      LAA closure. Based on MSCT, 48 LAA sizings (83%) resulted in a correct LAA
      closure device size selection, whereas with 2D-TEE sizing, only 33 measurements
      (57%) would have resulted in a correct device size selection (p<0.01). Using
      adapted Bland-Altman method, MSCT-based perimeter-derived mean diameter was shown
      to be the best parameter to guide LAA device size selection for a?~closed-enda?TM
      devices (Amulet, WatchmanFLX), whereas the maximal diameter was the best
      parameter for the a?~open-enda?TM Watchman device. CONCLUSIONS: Preprocedural
      MSCT-based LAA closure device size selection proves to be a more accurate method
      than conventional 2D-TEE-based sizing. Depending on the LAA closure device
      design, perimeter-derived mean diameter or maximal diameter could be the better
      sizing method.

PMID- 28761681
TI  - Smoking intensity and duration is associated with cardiac structure and function:
      the ECHOcardiographic Study of Hispanics/Latinos.
AB  - OBJECTIVE: Cardiovascular disease is the leading cause of death in smokers and
      this relationship is complicated by the multiplicity of cardiovascular effects of
      smoking. However, the relationship between intensity and duration of cigarette
      smoking and echocardiographic measures of right and left ventricular structure
      and function has been poorly studied. METHODS: We examined ECHO-SOL
      (Echocardiographic Study of Hispanics/Latinos) participants, a subset of the
      Hispanic Community Health Study/Study of Latinos. Participants were administered
      a detailed tobacco exposure questionnaire and a comprehensive echocardiography
      exam. Multivariable linear regression models (adjusted for age, sex, obesity,
      hypertension and diabetes statuses) were performed using sampling weights.
      Statistical significance was defined at p<0.01. RESULTS: There were 1818 ECHO-SOL
      participants (57.4% women, mean age 56.4 years). Among current smokers (n=304),
      increased duration of smoking, as measured by a younger age of smoking
      initiation, was significantly associated with higher mean left ventricular mass
      (LVM) and lower right ventricular (RV) function (lower right ventricular stroke
      volumes). More cigarettes smoked per day was significantly associated with higher
      mean LVM, worse diastolic function (higher E/e' ratio), worse LV geometry
      (increased relative wall thickness) and worse RV function (decreasing right
      ventricular stroke volume). Among current smokers, higher mean lifetime pack
      years (a combined measure of smoking intensity and duration) was associated with
      higher LVM, worse LV geometry, worse diastolic function, greater RV dilatation
      and worse RV function. CONCLUSIONS: There is a dose-response relationship between
      intensity and duration of cigarette tobacco smoking with unfavourable changes of
      multiple measures of right-sided and left-sided cardiac structure and function.

PMID- 28761683
TI  - Mortality and oral anticoagulants in the Food and Drug Administration Adverse
      Event Reporting System.
AB  - OBJECTIVE: The comparative crude death rates (CDR) among non-vitamin K antagonist
      oral anticoagulants (NOACs) are unknown. Further, whether NOACs improve survival
      when compared with warfarin is also unclear. We compared CDR co-reported for four
      NOACs combined or separately versus warfarin within the US Food and Drug
      Administration (FDA) Adverse Event Reporting System (FAERS) database. METHODS: We
      selected CDR from the FAERS database linked to four NOACs and warfarin. The
      primary endpoints were differences in proportional reporting ratios (PRRs), and
      Chi-Square (chi2)for dabigatran, rivaroxaban, apixaban and edoxaban when compared
      with warfarin. RESULTS: The FAERS database contains significantly less death
      reports associated with all NOACs combined (14 917 out of 128 267 reports
      (11.63%); PRR=1.089; chi2=70.0; p=6.05e-17) than for warfarin (19 493 out of 153
      911 reports (12.67%)). The numbers for rivaroxaban (6318 out of 64 512 reports or
      (9.79%); PRR=1.293; chi2=359.4; p=3.72e-80), apixaban (1693 out of 17 789 reports
      (9.52%); PRR=1.331; chi2=145.8; p=1.43e-33) and edoxaban (53 out of 755 reports
      (7.02%); PRR=1.804; chi2=21.18; p=4.18e-06) were favourable as compared with
      warfarin, while the numbers of fatalities co-reported with dabigatran (6989 out
      of 46 250 reports (15.11%); PRR=0.838; chi2=185.2; p=3.61e-42) were higher than
      for warfarin. CONCLUSION: Overall, based on these CDR, NOACs appear to be
      associated with a mortality benefit over warfarin. Among NOACs, we observed
      remarkably similar for factor Xa inhibitors (rivaroxiban, apixaban and edoxaban)
      but unfavourable signal for the direct thrombin inhibitor (dabigatran). However,
      these data are clearly not sufficient to change the prescription patterns.

PMID- 28761684
TI  - Osteopontin predicts clinical outcome in patients after treatment of severe
      aortic stenosis with transcatheter aortic valve implantation (TAVI).
AB  - OBJECTIVE: Osteopontin (OPN) is an extracellular matrix protein that plays an
      integral role in myocardial remodelling and has previously been shown to be a
      valuable biomarker in cardiovascular disease. Because of the concentric
      myocardial hypertrophy associated with severe, symptomatic aortic stenosis (AS),
      we hypothesised that OPN expression may have a prognostic value in patients
      undergoing transcatheter aortic valve implantation (TAVI). METHODS: We
      prospectively included 217 patients undergoing TAVI between February 2011 and
      December 2013 with a median follow-up of 349 days. Twenty healthy individuals
      from the same age range free from structural heart disease served as controls.
      The primary endpoint for the analysis was survival time. RESULTS: Median
      preprocedural OPN levels (675 ng/mL; IQR 488.5-990.5 ng/mL) were significantly
      higher in patients with severe aortic valve stenosis compared with healthy
      controls (386 ng/mL; IQR 324.5-458, p<0.001). Patients with increased OPN values
      showed at baseline a decreased 6 min walk test performance, increased rates of
      atrial arrhythmia, and an increased risk of death during follow-up (HR 2.2; 95%
      CI 1.3 to 3.5 for the comparison of the highest vs lowest OPN quartile). Multiple
      Cox regression analysis demonstrated that OPN improves the prediction of an
      adverse prognosis further than N-terminal probrain natriuretic peptide.
      CONCLUSIONS: OPN levels at baseline are associated with adverse outcomes in
      patients with severe, symptomatic AS undergoing TAVI.

PMID- 28761685
TI  - Two-year clinical outcomes of patients treated with the dual-therapy stent in a
      1000 patient all-comers registry.
AB  - OBJECTIVE: The dual-therapy stent combines an abluminal biodegradable drug
      eluting coating, with a 'pro-healing' luminal layer. This bioengineered layer
      attracts circulating endothelial progenitor cells that can differentiate into
      normal endothelium. Rapid endothelialisation of the stent might allow safe short
      dual antiplatelet therapy. We aim to assess clinical outcomes in patients treated
      with this novel device at 2-year follow-up. METHODS: A total of 1000 patients
      were included in the REMEDEE Registry to evaluate clinical outcomes after
      treatment with the dual-therapy stent. This prospective, multicentre, European
      registry included all-comers patients, which resulted in a high-risk patient
      population. Target lesion failure (TLF), a combined endpoint consisting of
      cardiac death, target vessel myocardial infarction (tv-MI) and target lesion
      revascularisation (TLR), at 2-year follow-up was the primary focus of this
      analysis. Subgroup analyses were performed according to diabetes mellitus (DM),
      gender, age, acute coronary syndrome, smoking, hypertension,
      hypercholesterolaemia, previous stroke, peripheral vascular disease and chronic
      renal failure. RESULTS: TLF at 2 years was observed in 84 patients (8.5%), with
      3.0% cardiac death, 1.2% tv-MI and 5.9% TLR. Definite stent thrombosis at 2 years
      was 0.6%. In the presence of DM or chronic renal failure, a higher TLF was
      observed. CONCLUSIONS: The dual-therapy stent shows favourable clinical outcomes
      from 12 months onwards. Two years after stent placement, low TLF and very low
      stent thrombosis rates are observed in this large prospective all-comers cohort
      study. TRIAL REGISTRATION NUMBER: NCT01874002; Results.

PMID- 28761686
TI  - Quality of life and psychological and gastrointestinal symptoms after
      cholecystectomy: a population-based cohort study.
AB  - OBJECTIVE: The study aims to examine gastrointestinal symptoms, quality of life
      and the risk of psychological symptoms after cholecystectomy. DESIGN: This is a
      prospective population-based cohort study based on the Nord-Trondelag Health
      Study (HUNT) Norway. HUNT is a repeated health survey of the county population
      and includes a wide range of health-related items. In the present study, all 3
      HUNT surveys were included, performed between 1984 and 2008. Selected items were
      scores on quality of life, the Hospital Anxiety and Depression Scale (HADS) and
      selected gastrointestinal symptoms. Participants who underwent cholecystectomy
      for gallstone disease between 1 January 1990 and until 1 year before attending
      HUNT3 were compared with the remaining non-operated cohort. Associations between
      cholecystectomy and the postoperative scores and symptoms were assessed by
      multivariable regression models. RESULTS: Participants in HUNT1, HUNT2 and HUNT3
      were 77 212 (89.4% of those invited), 65 237 (69.5%) and 50 807 (54.1%),
      respectively. In the study period, 931 participants were operated with
      cholecystectomy. Cholecystectomy was associated with an increased risk of
      diarrhoea and stomach pain postoperatively. In addition, cholecystectomy was
      associated with an increased risk of nausea postoperatively in men. We found no
      associations between cholecystectomy and quality of life, symptoms of anxiety and
      depression, constipation, heartburn, or acid regurgitation following surgery.
      CONCLUSIONS: In this large population-based cohort study, cholecystectomy was
      associated with postoperative diarrhoea and stomach pain. Cholecystectomy for
      gallstone colic was associated with nausea in men. There were no associations
      between quality of life, symptoms of anxiety and depression, constipation,
      heartburn, or acid regurgitation.

PMID- 28761687
TI  - Systemic sclerosis is associated with specific alterations in gastrointestinal
      microbiota in two independent cohorts.
AB  - OBJECTIVE: To compare faecal microbial composition in patients with systemic
      sclerosis (SSc) from 2 independent cohorts with controls and to determine whether
      certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.
      DESIGN: Adult patients with SSc from the University of California, Los Angeles
      (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in
      this study (1:1:1). All participants provided stool specimens for 16S rRNA
      sequencing. Linear discriminant analysis effect size demonstrated genera with
      differential expression in SSc. Differential expression analysis for sequence
      count data identified specific genera associated with GIT symptoms as assessed by
      the GIT 2.0 questionnaire. RESULTS: The UCLA-SSc and OUH-SSc cohorts were similar
      in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6
      (2.5-16.4) and 7.0 (1.0-19.2) years, respectively), gender distribution (88% and
      71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6)
      and 0.6 (0.5), respectively). Principal coordinate analysis illustrated
      significant microbial community differences between SSc and controls (UCLA:
      p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of
      commensal genera deemed to protect against inflammation, such as Bacteroides
      (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly
      higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with
      controls. Increased abundance of Clostridium was associated with less severe GIT
      symptoms in both cohorts. CONCLUSIONS: The present analysis detected specific
      aberrations in the lower GIT microbiota of patients with SSc from 2
      geographically and ethnically distinct cohorts. These findings suggest that GIT
      dysbiosis may be a pathological feature of the SSc disease state.

PMID- 28761688
TI  - Epidemiology of coeliac disease in a single centre in Southern Derbyshire 1958
      2014.
AB  - OBJECTIVE: To determine trends in diagnosis of coeliac disease (CD) in patients
      attending a single centre 1958-2014 and provide figures for prevalence and
      incidence in those born in Derby city over 4 decades. To explore a link between
      deprivation and prevalence and characteristics of CD in Asians. DESIGN: An
      unselected, consecutive series of 2410 adult patients with CD diagnosed in the
      catchment area of the Derby hospitals was identified. 1077 born within Derby city
      identified by postcodes was used to determine changes in prevalence and incidence
      over 4 decades. 191 patients were Asian. Population numbers were obtained from
      National Census information. RESULTS: In the quinquennium 2010-2014, 20 times
      more patients were diagnosed than during 1975-1979. 27% were diagnosed at >=60
      years. A paucity of diagnoses in young men was observed. Women were diagnosed
      most often in age band >=35<45, 15 years earlier than men. The largest increase
      in diagnosis rates occurred in young women and the elderly. In 2014, overall
      prevalence was 1:188; women 1:138. 4.6% of the variation was attributed to
      deprivation. Diagnosis rates in Asians increased markedly although only 5% were
      diagnosed at >=60 years, much lower than for whites. CONCLUSIONS: The dramatic
      increase in number of patients with CD presents challenges for follow-up and new
      models of care need to be explored. Healthcare workers should be alert to the
      diagnosis in young men and elderly Asians. A dedicated coeliac clinic is an
      excellent facility to increase diagnosis rates.

PMID- 28761689
TI  - Efficacy of dietary and physical activity intervention in non-alcoholic fatty
      liver disease: a systematic review.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of
      chronic liver disease worldwide, with prevalence above 30% in many adult
      populations. Strongly associated with obesity, weight loss through diet and
      physical activity is the mainstay of its management. Weight loss can be difficult
      to achieve and maintain however, and uncertainty exists as to which lifestyle
      changes are most effective. OBJECTIVE: The aim of this work was to systematically
      evaluate randomised controlled trials assessing diet, exercise or combination
      interventions aimed at reducing steatosis or markers of NAFLD activity. DESIGN:
      Medline, Scopus and Cochrane databases were searched from 1 January 1980 through
      to 31 July 2016, for intervention trials assessing the effects of diet, weight
      loss, exercise or any combination thereof, on NAFLD disease markers in human
      adults. Risk of publication bias and study quality was assessed using the
      American Dietetic Association Quality Criteria Checklist. RESULTS: From a total
      of 1710 identified records, 24 articles met the inclusion and exclusion criteria;
      6 assessed weight loss using dietary restriction, 10 assessed exercise and 8 were
      combination interventions. While all of the trials demonstrated significant
      reduction in steatosis and/or markers of NAFLD activity, combination
      interventions appear to be the most effective at improving NAFLD. Results suggest
      that 5-10% weight loss using a modestly hypocaloric diet of 500 kcal less per day
      than calculated energy requirement, in combination with 30-60 min exercise on 3-5
      days per week should be recommended. CONCLUSIONS: We conclude this amount of
      weight loss is achievable in the trial setting but is challenging in the clinical
      environment. High-intensity, multidisciplinary intervention in specialist clinics
      is likely to be required in order to manage NAFLD by lifestyle modification
      alone. This systematic review protocol was registered prospectively at PROSPERO
      as CRD42016032764.

PMID- 28761690
TI  - Duodenal biopsies for the diagnosis of coeliac disease: are we adhering to
      current guidance?
AB  - BACKGROUND: The British Society of Gastroenterology guidelines recommend taking
      at least four duodenal biopsy specimens at the time of upper gastrointestinal
      (UGI) endoscopy if coeliac disease (CD) is suspected and it has been shown to
      increase the diagnostic yield of CD. We assessed the compliance to these
      guidelines within our institution. We then applied measures to improve our
      compliance rate and assessed the resulting impact on our diagnostic rate of CD.
      METHODS: We performed a retrospective audit of electronic records for all
      patients, with no prior diagnosis of CD, who underwent UGI endoscopy with
      duodenal biopsies between August 2014 and May 2015. We implemented measures to
      raise awareness among endoscopy users at our institution and carried out a
      reaudit between February and May 2016. RESULTS: 924 patients were found to be
      eligible in the first part of the study and 278 in the second part. The
      proportion of patients who had >=4 biopsy specimens submitted increased from
      21.9% to 60.8% (p<0.001). The diagnostic rate of CD increased from 3.5% in the
      audit group to 7.6% in the reaudit group (p=0.004). A positive serology result
      and suspected CD as an indication for biopsy were found to be independent
      predictors of the likelihood of complying with guidelines. CONCLUSIONS: Our study
      suggests that taking <4 duodenal biopsy specimens to assess for the presence of
      CD may lead to the diagnosis of CD being missed. Simple measures can improve the
      local compliance rate to current guidelines.

PMID- 28761691
TI  - Impact of feedback and monitoring on colonoscopy withdrawal times and polyp
      detection rates.
AB  - BACKGROUND: Previous studies have shown colonoscopy withdrawal time (WT) to be a
      reliable surrogate indicator for polyp detection rate (PDR) and adenoma detection
      rate (ADR) in colonoscopy. Our aim was to assess the impact of feedback and
      monitoring of WT on PDR in routine colonoscopies with long-term follow-up.
      MATERIALS AND METHODS: A total of 307 colonoscopies were performed in three
      separate clinical scenarios. First, PDR and WT were recorded without the staff
      being aware of the specific objective of the study. Before the second scenario,
      the staff was given interventional information and feedback on WTs and PDRs from
      the first scenario and was encouraged to aim for a minimum WT of 8 min. Retention
      of knowledge gained was reassessed in the third scenario 1 year later. RESULTS:
      The PDR in the first two scenarios differed significantly (p<0.01), with a more
      than 90% increase in PDR after intervention from 22% to 42% (95% CI 1.44 to
      4.95), although the mean WT did not change (6.8 vs 7.2 min; p>0.05). The increase
      in PDR between the first and second scenarios was retained in the third follow-up
      scenario 1 year later where the WT of both polyp-positive and polyp-negative
      colonoscopies was found to be longer. CONCLUSIONS: PDR almost doubled from the
      first to the second scenario of a real-life colonoscopy setting, indicating that
      awareness of WT is crucial. The knowledge gained from this intervention in
      routine practice was even retained after a year.

PMID- 28761692
TI  - Alteration in the gastric microbiota and its restoration by probiotics in
      patients with functional dyspepsia.
AB  - OBJECTIVE: The objective of this study was to comparatively analyse the gastric
      fluid (GF) microbiota between patients with functional dyspepsia (FD) and healthy
      controls (HC), and to assess the effect of probiotics on the microbiota. DESIGN:
      Twenty-four Japanese patients with FD who met the Rome III definition and 21 age
      matched and gender-matched HC volunteers were enrolled. The patients with FD had
      been treated with LG21, a probiotic strain. The GF was sampled after an overnight
      fast using a nasogastric tube. The bile acids concentration was determined by
      ELISA. The V3-V4 region of 16S rRNA gene was amplified using bacterial DNA from
      the GF, and then about 30 000 high-quality amplicons per sample were grouped into
      operational taxonomic units for analyses. RESULTS: The ratio of GF samples in
      which the bile acids were detectable was significantly greater in the FD than in
      the HC groups. In the bacterial composition analysis at the phylum level, the GF
      microbiota had a Bacteroidetes > Proteobacteria abundance and an absence of
      Acidobacteria in the FD group, in contrast, the GF microbiota had a Bacteroidetes
      < Proteobacteria abundance and the presence of Acidobacteria in the HC group.
      Probiotic therapy in patients with FD shifted the composition of the GF
      microbiota to that observed in the HC volunteers. CONCLUSIONS: Alteration in the
      GF microbiota was found in patients with FD compared with HC volunteers. Reflux
      of the small intestinal contents, including bile acid and intestinal bacteria, to
      the stomach was suggested to induce a bacterial composition change and be
      involved in the pathophysiology underlying FD. Probiotics appear effective in the
      treatment of FD through the normalisation of gastric microbiota. TRIAL
      REGISTRATION NUMBER: UMINCTR 000022026; Results.

PMID- 28761693
TI  - Effect of dexmedetomidine in the prophylactic endoscopic injection sclerotherapy
      for oesophageal varices: a study protocol for prospective interventional study.
AB  - BACKGROUND: Dexmedetomidine (DEX) is a novel, highly selective alpha2
      adrenoceptor agonist that elicits sedative, amnestic, sympatholytic and analgesic
      effects in patients. Several Japanese investigators have reported the clinical
      usefulness of DEX for sedation in endoscopic therapies for gastrointestinal
      malignancies; however, there have been limited data regarding the usefulness and
      safety of DEX for sedation during endoscopic procedures for oesophageal varices
      (OVs), such as endoscopic injection sclerotherapy (EIS). In this prospective,
      single-arm interventional study, we aimed to elucidate these issues. METHODS:
      Patients who require two or more sessions of prophylactic EIS for the treatment
      of OVs will be enrolled in this prospective interventional study. EIS procedures
      include two methods: (1) sedation during endoscopic procedures will be performed
      using conventional methods (pentazocine (PNZ) and midazolam (MDZ)), and (2)
      sedation during endoscopic procedures will be performed using PNZ, low-dose MDZ
      and DEX. These two methods were randomly assigned in the first and second EIS.
      The effect and safety of these two procedures with respect to patient sedation
      are to be compared with the degree of sedation evaluated using the Bispectral
      Index monitoring system (Aspect Medical Systems, Norwood, Massachusetts, USA).
      ETHICS AND DISSEMINATION: This study received approval from the Institutional
      Review Board at Hyogo College of Medicine (approval no. 2324). The authors are
      committed to publishing the study results as widely as possible in peer-reviewed
      journals, and to ensuring that appropriate recognition is provided to everyone
      who is working on this study. TRIAL REGISTRATION NUMBER: UMIN000026688; Pre
      results.

PMID- 28761694
TI  - The effect of minimalist footwear and instruction on running: an observational
      study.
AB  - BACKGROUND: It is not known whether the effects on altered running style which
      are attributed to minimalist footwear can be achieved by verbal instructions in
      standard running shoes (SRS). AIM: To explore the effect of Vibram FiveFingers
      (VFF) versus SRS plus running instruction on lower extremity spatiotemporal
      parameters and lower limb joint kinematics. METHODS: 35 healthy subjects (mean=30
      years, 18 females) were assessed on two occasions with 3D motion analysis. At
      each session subjects ran on a treadmill (3.58 m/s) for 2 min in either VFF or
      SRS (randomised order); with and without running instruction. Differences between
      spatiotemporal parameters and lower limb joint kinematics between conditions were
      assessed using a 2x2 repeated-measures ANOVA. RESULTS: Wearing VFF significantly
      increased cadence (p<0.001) and reduced stride length (p<0.01). Prior to initial
      contact, both instruction and VFF significantly increased foot (p<0.001 and
      p=0.02, respectively) and ankle (p<0.001 and p=0.02, respectively)
      plantarflexion, while wearing VFF significantly increased knee extension
      (p=0.04). At initial contact, instruction significantly increased knee flexion
      (p=0.04), and foot (p=0.001) and ankle (p=0.03) plantarflexion. At mid-stance and
      toe-off, instruction significantly increased knee flexion (p=0.048 and p<0.001,
      respectively) and foot plantarflexion (p<0.001 and p=0.01, respectively).
      Instruction had a greater effect on increasing knee flexion (p=0.007) and
      plantarflexion angle (p<0.001) when subjects wore SRS and VFF, respectively.
      CONCLUSION: Alterations in spatiotemporal parameters observed when running in VFF
      are likely to be attributable to the minimalist footwear. However, the kinematic
      adaptations observed following instruction suggests that changes in joint angles
      previously attributed to minimalist footwear alone may be similarly achieved with
      instruction.

PMID- 28761695
TI  - Misinterpretation of the Borg's Rating of Perceived Exertion Scale by patients
      with panic disorder during ergospirometry challenge.
AB  - INTRODUCTION: The most widely used instrument to measure perceived exertion or
      exercise intensity is the Borg's Rating of Perceived Exertion (RPE) Scale. Panic
      attacks are aversive experiences that may be triggered by bodily sensations such
      as palpitations, breathlessness or dizziness due to increasing autonomic
      distress, prior sensitisation to panic and fear conditioning. The consequence is
      catastrophic interpretation of bodily sensations of arousal in general, which can
      lead to misinterpretation of exertion or exercise intensity. PURPOSE: To verify
      the effectiveness of the Borg's RPE Scale as a measure of perceived effort in
      panic disorder subjects. METHODS: The study enrolled 72 subjects: the control
      group (C, healthy sedentary subjects, n=30) and patients with panic disorder (PD,
      n=42). All subjects were submitted to an ergospirometry challenge. Perceived
      exertion RPE scores and heart rate at 90% VO2max were compared between groups.
      RESULTS: Patients with PD showed lower levels of maximal oxygen consumption, when
      compared with C group [VO2max (mL/kg/min): PD=29.42+/-6.50xC=34.51+/-5.35;
      Student's t-test=-3.51; p <0.05]. Furthermore, among PD subjects, the maximum
      heart rate during ergospirometry challenge was lower than expected [predict max
      HR (bpm)=200.85+/-6.33xheart rate test (bpm)=178.86+/-7.28; Z=-5.64; p<0.05].
      Perceived exertion, as measured by RPE, was also overestimated in relation to
      heart rate at 90% of maximum oxygen consumption compared with controls
      (RPE90%VO2max: PD=18.93+/-0.55xC=16.67+/-0.60; U=8.00; Z=7.42; p<0.05).
      CONCLUSIONS: The present study findings suggest that the Borg's RPE Scale may not
      be an appropriate measure of subjective exertion among subjects with panic
      disorder performing a cardiopulmonary exercise test.

PMID- 28761696
TI  - Ankle syndesmosis repair and rehabilitation in professional rugby league players:
      a case series report.
AB  - BACKGROUND/AIM: The distal tibiofibular joint is described as a syndesmosis.
      Traditionally, severe syndesmotic injuries with diastasis have been treated
      surgically with screw fixation. This case series details an ankle syndesmosis
      tightrope repair and an accelerated rehabilitation protocol that reduces the
      amount of time to return to professional rugby league in the UK. The aim of this
      study was to describe players' journey from injury, through diagnosis to surgery,
      rehabilitation and return to participation, detailing time scales and methods
      used at each stage to highlight the change in current practice. METHODS: Players
      were identified via a single orthopaedic surgeon in the UK who specialises in
      ankle syndesmosis repair. Between January 2010 and September 2015, adult men
      playing full-time professional rugby league in the UK Super League with ankle
      syndesmosis injuries were identified. RESULTS: Eighteen players from six
      different clubs were included. The most common mechanism of injury was forced
      dorsiflexion/eversion. The average return to participation was 64 days (SD 17.2,
      range 38-108). This compares favourably to reports of between 120 and 180 days
      following screw fixation. CONCLUSION: Ankle syndesmosis tightrope repair and an
      accelerated rehabilitation protocol is as safe as traditional methods. The
      accelerated rehabilitation protocol promotes early weight-bearing and has shown
      to expedite the return to sport for professional Rugby League players. It is
      possible to return to sport 2 months after a tightrope repair and accelerated
      rehabilitation, compared with 3-6 months post screw fixation. This is extremely
      encouraging for the professional sporting population.

PMID- 28761697
TI  - Cardiorespiratory fitness and physical function in children with cancer from
      diagnosis throughout treatment.
AB  - BACKGROUND: Children with cancer experience severe reductions in physical fitness
      and functionality during and following intensive treatment. This may negatively
      impact their quality of life. PURPOSE: To describe the physical capacity and
      functionality of children with cancer during and after treatment as well as the
      feasibility of physical activity intervention in the Rehabilitation including
      Social and Physical activity and Education in Children and Teenagers with Cancer
      study. PATIENTS AND METHODS: The study included children diagnosed from January
      2013 to April 2016 with paediatric cancer or Langerhans cell histiocytosis, all
      treated with chemotherapy. Seventy-five of 78 consecutively eligible children
      (96.2%) were included. Median age was 11 years (range 6-18). The physical
      capacity and function were assessed based on testing of physical strength,
      balance and cardiorespiratory fitness. Children were tested at diagnosis, 3 and 6
      months after diagnosis and 1 year after cessation of treatment. The feasibility
      evaluation was inspired by the criteria for reporting the development and
      evaluation of complex interventions in healthcare. RESULTS: All children
      participated in the physical intervention programme with no dropouts. Strenuous
      physical exercise and physiological testing during paediatric cancer treatment
      was safe and feasible, with only five minor adverse events during the
      intervention. Cardiorespiratory fitness was significantly lower in children with
      cancer than norms for healthy age-matched children at diagnosis (difference 19.1
      mL/kg/min, 95% CI 15.4 to 22.7; p <0.0001), during treatment 3 and 6 months from
      diagnosis (difference 21.0 mL/kg/min, 95% CI 17.4 to 24.6; p <0.0001 and
      difference 21.6 mL/kg/min, 95% CI 17.3 to 25.8; p <0.0001, respectively) and 1
      year after cessation of treatment (difference 6.9 mL/kg/min, 95% CI 1.1 to 12.7;
      p <0.0072). Furthermore, children with cancer experienced a pronounced decline in
      physical function. CONCLUSION: This study shows that it is safe and feasible to
      perform strenuous physical exercise and testing during paediatric cancer
      treatment and that children with cancer have significantly lower physical
      capacity and functionality than healthy age-matched norms. TRIAL REGISTRATION
      NUMBER: ClinicalTrials.gov: NCT01772862.

PMID- 28761698
TI  - Sports injuries and illnesses in first-year physical education teacher education
      students.
AB  - BACKGROUND/AIM: We aimed to investigate the magnitude and characteristics of
      injuries and illnesses in Dutch physical education teacher education (PETE)
      students. METHODS: During the first 21 weeks of the academic year, 245 first-year
      students registered their health problems online using the Oslo Sports Trauma
      Research Centre (OSTRC) Questionnaire on Health Problems. RESULTS: A total of 276
      injuries, 140 illnesses and 69 unclassified health problems were reported. We
      found an injury incidence rate of 11.7 injuries per 1000 hours (95% CI 10.4 to
      13.2). Injury characteristics were: 42% overuse injuries, 62% causing absence
      from sports (median injury time loss=2 days) and 64% reinjuries. Most injuries
      were located at the knee, lower leg (anterior) and ankle. The duration of the
      illnesses was short (<1 week). SUMMARY AND CONCLUSIONS: We implemented a new
      registration method in the PETE academic programme. The results show that the
      risk for health problems is high for PETE students. Prevention is necessary, and
      to decrease injuries prevention programmes should focus on the lower extremities.

PMID- 28761699
TI  - High-intensity flywheel exercise and recovery of atrophy after 90 days bed--rest.
AB  - AIMS: To investigate differential muscle atrophy during bed-rest, the impact of a
      high-intensity concentric-eccentric (flywheel) resistance exercise countermeasure
      and muscle recovery after bed-rest. METHODS: Twenty-five healthy male subjects
      underwent 90 dayshead-down tilt bed-rest. Volume of individual lower-limb muscles
      was measured via MRI before, twice during and four times up to 1 year after bed
      rest. Subjects were either inactive (n=16) or performed flywheel exercise every
      third day of bed-rest (n=9). Functional performance was assessed via
      countermovement jump. RESULTS: On 'intent-to-treat' analysis, flywheel prevented
      atrophy in the vasti (p<0.001) and reduced atrophy in the hip adductor/extensor
      adductor magnus (p=0.001) and ankle dorsiflexors/toe flexors (soleus (p<0.001),
      gastrocnemius medialis (p<0.001), gastrocnemius lateralis (p=0.02), and tibialis
      posterior with flexor digitorum longus (p=0.04)). Flywheel exercise was not
      effective for the hamstrings, gracilis, sartorius, peroneals and anterior tibial
      muscles. Muscle atrophy in vasti, soleus, gastrocnemius medialis, gastrocnemius
      lateralis and adductor magnus correlated with losses in countermovement jump
      performance. Muscle volume recovered within 90 days after bed-rest, however long
      term after bed-rest, the inactive subjects only showed significantly increased
      muscle volume versus prebed-rest in a number of muscles including soleus (+4.3%),
      gastrocnemius medialis (+3.9%) and semimembranosus (+4.3%). This was not
      associated with greater countermovement jump performance. CONCLUSION: The
      exercise countermeasure was effective in preventing or reducing atrophy in the
      vasti, adductor magnus and ankle dorsiflexors/toe flexors but not the hamstrings,
      medial thigh muscles or peroneals and dorsiflexor muscles. TRIAL REGISTRATION
      NUMBER: NCT00311571; results.

PMID- 28761700
TI  - A novel treadmill protocol for exercise testing in children: the British Columbia
      Children's Hospital protocol.
AB  - BACKGROUND: Exercise testing in children is widely recommended for a number of
      clinical and prescriptive reasons. Many institutions continue to use the Bruce
      protocol for treadmill testing; however, with its incremental changes in speed
      and grade, it has challenges for practical application in children. We have
      developed a novel institutional protocol (British Columbia Children's Hospital
      (BCCH)), which may have better utility in paediatric populations. AIM: To
      determine if our institutional protocol yields similar peak responses in minute
      ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2),
      respiratory exchange ratio (RER), metabolic equivalents (METS) and heart rate
      (HR) when compared with the traditional Bruce protocol. METHODS: On two different
      occasions, 70 children (boys=33; girls=37) aged 10-18 years completed an exercise
      test on a treadmill using each of the protocols. During each test, metabolic gas
      exchange parameters were measured. HR was monitored continuously during exercise
      using an HR monitor. RESULTS: Physiological variables were similar between the
      two protocols (median (IQR); rs): VE (L/min) (BCCH=96.7 (72.0-110.2); Bruce=99.2
      (75.6-120.0); rs=0.95), peak VO2 (mL/min) (BCCH=2897 (2342-3807); Bruce=2901
      (2427-3654); rs=0.94) and METS (BCCH=16.2 (14.8-17.7); Bruce=16.4 (14.7-17.9);
      rs=0.89). RERs were similar (BCCH=1.00 (0.96-1.02); Bruce=1.03 (0.99-1.07);
      rs=0.48). Total exercise time (in seconds) was longer for the BCCH protocol:
      BCCH=915 (829-1005); Bruce=810 (750-919); rs=0.67. CONCLUSION: The BCCH protocol
      produces similar peak exercise responses to the Bruce protocol and provides an
      alternative for clinical exercise testing in children.

PMID- 28761702
TI  - Static stretching does not enhance recovery in elite youth soccer players.
AB  - BACKGROUND: Static stretching (SS) is a recovery intervention used for the
      reduction of muscle soreness postexercise. The effects of SS on elite young
      footballers have received little attention, and therefore the aim of this study
      was to assess the effects of SS on muscle recovery following competitive soccer
      matches in elite young footballers. METHODS: Ten male participants (16+/-1 years)
      were recruited from an English Premier League professional soccer academy. Using
      a controlled crossover design, participants followed one of two recovery
      interventions (SS or passive recovery (PR)) immediately following completion of
      competitive soccer matches. Muscle oedema, creatine kinase (CK), countermovement
      jump with arms (CMJA) performance and perceived muscle soreness were assessed
      before, immediately after and 48 hours postmatch. RESULTS: Competitive soccer
      matches significantly induced muscle damage, with time intervals of perceived
      soreness and CK showing significant increases (p<0.05), and CMJA showing
      significant decreases between prematch, postmatch and 48 hours postmatch for both
      SS and PR (p<0.05). Comparisons of the absolute effects of SS with PR only
      revealed significant decreases for CK 48 hours postmatch (p<0.05) as a result of
      SS intervention. CONCLUSION: The current study demonstrated competitive soccer
      matches induced muscle damage, which may have detrimental effects on future
      performance within 24-48 hours postmatch. Furthermore, there was limited evidence
      to suggest SS would assist in the reduction of muscle soreness postexercise.
      Therefore, it can be argued that SS is not a beneficial recovery option for elite
      youth soccer players.

PMID- 28761701
TI  - High prevalence of self-reported injuries and illnesses in talented female
      athletes.
AB  - BACKGROUND: A thorough knowledge of the epidemiology and severity of injuries and
      illness in youth female elite sports is lacking due to the methodological
      challenges involved in recording them. In this study, the prevalence and
      incidence of injuries and illness are assessed among youth female elite athletes.
      Instead of solely focusing on time-loss injuries, our study included all
      substantial and non-substantial health problems (ie, injuries, mental problems
      and illnesses). METHODS: Sixty young elite Dutch female athletes (age: 16.6 years
      (SD: 2.3), weight: 58.3 kg (SD: 15.1), height: 154.1 cm (SD: 44.2)) participating
      in soccer (n=23), basketball (n=22) and gymnastic (n=15) talent development
      programmes were prospectively followed during one season (September 2014 to April
      2015). To collect health problem data, all athletes completed the Oslo Sports
      Trauma Research Center Questionnaire on Health Problems every other week. Main
      outcome measures were average prevalence of injury and incidence density of
      injury. RESULTS: At any given time, 47.9% of the athletes reported an injury (95%
      CI 43.6% to 52.6%) and 9.1% reported an illness (95% CI 5.1 to 19.0). The average
      injury incidence density was 8.6 per 1000 hours of athlete exposure. The average
      number of self-reported injuries per athlete per season was significantly higher
      in soccer athletes (4.3+/-2.7) than in basketball athletes (2.6+/-2.0) (p=0.03)
      and not significantly higher than in the gymnastic squad. The knee and the ankle
      were two of the most common injury locations for all squads. Knee injuries in
      basketball and soccer and heel injuries in the gymnastic squad had the highest
      impact on sports participation. CONCLUSION: High prevalence of self-reported
      injuries among talented female athletes suggests that future efforts towards
      their prevention are warranted.

PMID- 28761703
TI  - Validation of the Global Physical Activity Questionnaire for self-administration
      in a European context.
AB  - BACKGROUND/AIM: Little is known about the measurement properties of the self
      administered Global Physical Activity Questionnaire (GPAQ) in Europe. The aim was
      to validate the self-administered GPAQ against accelerometry in Switzerland in
      German, French and Italian. METHODS: Participants of this cross-sectional study
      were recruited among members of the Swiss Food Panel (German-speaking and French
      speaking samples) and as a convenience sample (Italian-speaking sample). They
      completed the GPAQ and wore an Actigraph GT3X+ accelerometer during 7 days in
      2014/2015. GPAQ and accelerometer data on total physical activity and different
      intensities, as well as sitting time, were compared using Spearman correlations
      and Bland-Altman plots. RESULTS: Complete data were available for 354
      participants (50.6% women, mean age: 47.0 years) on physical activity, and for
      366 on sitting time. Correlations were highest for vigorous physical activity
      (r=0.46) and sitting time (r=0.47). A significant sex difference was apparent for
      vigorous physical activity (men: r=0.35 vs women: r=0.55; p=0.02). Some age
      differences were present especially for total physical activity, with the lowest
      correlations found for those aged 60+ years. The correlation for sitting time was
      significantly higher in the youngest age group (r=0.61) compared with the middle
      (r=0.38, p=0.01) and the oldest age groups (r=0.37, p=0.03). Total physical
      activity was 2.8 times higher according to the GPAQ than to accelerometer data.
      CONCLUSIONS: The self-administered version of the GPAQ showed fair-to-moderate
      validity in the three languages tested, both for men and women and individuals
      aged <=60 years. For older individuals, a careful interpretation of total
      physical activity is required.

PMID- 28761704
TI  - CPR performance in the presence of audiovisual feedback or football shoulder
      pads.
AB  - OBJECTIVE: The initiation of cardiopulmonary resuscitation (CPR) can be
      complicated by the use of protective equipment in contact sports, and the rate of
      success in resuscitating the patient depends on the time from incident to start
      of CPR. The aim of our study was to see if (1) previous training, (2) the
      presence of audiovisual feedback and (3) the presence of football shoulder pads
      (FSP) affected the quality of chest compressions. METHODS: Six basic life support
      certified athletic training students (BLS-ATS), six basic life support certified
      emergency medical service personnel (BLS-EMS) and six advanced cardiac life
      support certified emergency medical service personnel (ACLS-EMS) participated in
      a crossover manikin study. A quasi-experimental repeated measures design was used
      to measure the chest compression depth (cm), rate (cpm), depth accuracy (%) and
      rate accuracy (%) on four different conditions by using feedback and/or FSP. Real
      CPR Help manufactured by ZOLL (Chelmsford, Massachusetts, USA) was used for the
      audiovisual feedback. Three participants from each group performed 2 min of chest
      compressions at baseline first, followed by compressions with FSP, with feedback
      and with both FSP and feedback (FSP+feedback). The other three participants from
      each group performed compressions at baseline first, followed by compressions
      with FSP+feedback, feedback and FSP. RESULTS: CPR performance did not differ
      between the groups at baseline (median (IQR), BLS-ATS: 5.0 (4.4-6.1) cm, 114(96
      131) cpm; BLS-EMS: 5.4 (4.1-6.4) cm, 112(99-131) cpm; ACLS-EMS: 6.4 (5.7-6.7) cm,
      138(113-140) cpm; depth p=0.10, rate p=0.37). A statistically significant
      difference in the percentage of depth accuracy was found with feedback (median
      (IQR), 13.8 (0.9-49.2)% vs 69.6 (32.3-85.8)%; p=0.0002). The rate accuracy was
      changed from 17.1 (0-80.7)% without feedback to 59.2 (17.3-74.3)% with feedback
      (p=0.50). The use of feedback was effective for depth accuracy, especially in the
      BLS-ATS group, regardless of the presence of FSP (median (IQR), 22.0 (7.3-36.2)%
      vs 71.3 (35.4-86.5)%; p=0.0002). CONCLUSIONS: The use of audiovisual feedback
      positively affects the quality of the depth of CPR. Both feedback and FSP do not
      alter the rate measurements. Medically trained personnel are able to deliver the
      desired depth regardless of the presence of FSP even though shallower chest
      compressions depth can be seen in CPR with FSP. A feedback device must be
      introduced into the athletic training settings.

PMID- 28761705
TI  - Changes in lung function during exercise are independently mediated by increases
      in deep body temperature.
AB  - BACKGROUND: This study examined whether an increase in deep body temperature
      contributes to increases in ventilatory flow indicative of bronchodilatation.
      METHOD: The study employed a within-participant repeated measures design. Nine
      participants (mean (SD): age 22 (3) years; height 177.7 (8.3) cm; mass 80.2
      (19.1) kg) completed three conditions: exercise (EXERC; 30 min); 40 degrees C
      water immersion (IMM40; 30 min) to passively raise rectal temperature (Tre) and
      35 degrees C immersion (IMM35; 30 min) asa thermoneutral control for IMM40. A
      forced vital capacity (FVC) manoeuvre was performed at the start of the test and
      every 10 min thereafter. Forced expiratory volume in 1 s (FEV1), FEV1/FVC, 25%,
      50% and 75% maximal expiratory flow during FVC (forced expiratory flow (FEF)25,
      FEF50, FEF75) were also measured. Data were compared using a repeated measures
      two-way analysis of variance, with a 0.05 alpha level. RESULTS: Rectal
      temperature (Tre) peaked after 30 min in the EXERC (mean (SD) 38.0 (0.3) degrees
      C) and IMM40 (38.2 (0.2) degrees C) conditions and both were higher (p<0.05) than
      at the corresponding time in the thermoneutral condition (37.2 (0.2) degrees C).
      At this time, FEV1 was 4.5 (0.6), 4.6 (0.3) and 4.4 (0.6) L, respectively. Tre,
      FEV1 and FEV1/FVC were greater in the IMM40 and EXERC conditions compared with
      the IMM35 condition. Interaction effects were evident for FEF50 and FEF75
      (p<0.05), being higher in IMM40 and EXERC conditions. CONCLUSION: Increasing deep
      body temperature, independently, contributes to the increased airflow ascribed to
      bronchodilatation when exercising.

PMID- 28761706
TI  - Leisure time physical activity and quality of life in medical students: results
      from a multicentre study.
AB  - BACKGROUND/AIM: We evaluated the association between leisure time physical
      activity (PA) and quality of life (QoL) in medical students. Our hypothesis was
      that there was a positive association between volume of PA and various domains of
      perception of QoL. METHODS: Data were evaluated from a random sample of 1350
      medical students from 22 Brazilian medical schools. Information from participants
      included the WHO Quality of Life questionnaire-short form (WHOQOL-BREF), a
      questionnaire specifically designed to evaluate QoL in medical students (VERAS-Q)
      and questions for both global QoL self-assessment and leisure time PA. According
      to the amount of metabolic equivalents (METs) spend during PA, volunteers were
      divided into four groups, according to the volume of PA: (a) no PA; (b) low PA,
      <=540 MET min/week; (c) moderate PA, from 541 to 1260 MET min/week and (d) high
      PA, > 1261 MET min/week. RESULTS: Forty per cent of the medical students reported
      no leisure time PA (46.0% of females and 32.3% of males). In contrast, 27.2% were
      classified in the group of high PA (21.0% of females and 34.2% of males). We
      found significant associations between moderate and high levels of PA and better
      QoL for all measurements. For low levels of PA, this association was also
      significant for most QoL measurements, with the exceptions of WHOQOL physical
      health (p=0.08) and social relationships (p=0.26) domains. CONCLUSION: We
      observed a strong dose-effect relationship between the volume of leisure time PA
      and QoL in both male and female medical students.

PMID- 28761707
TI  - Concussion guideline implementation perceptions and experiences among parents of
      community-level Australian Football junior players.
AB  - BACKGROUND/AIM: Concussion guidelines exist for multiple community sports.
      Parents are key stakeholders in guideline implementation and in appropriate
      responses following concussive injury. The purpose of this qualitative
      investigation was to understand how parents of community-level Australian
      Football (AF) players experience and perceive concussion guidelines in order to
      inform the design and implementation of concussion guidelines in community sport.
      METHODS: A cross-sectional qualitative approach was adopted to allow for an open
      and detailed exploration of the views of parents of junior community AF players
      (ie, those aged <16 years) regarding concussion guidelines of the AF League (AFL)
      the national governing body for AF. Participants were 15 parents of junior
      community AF players from two clubs affiliated with a large regional community AF
      League. RESULTS: The key experiences and perceptions of the parents included
      appreciation that the guidelines outlined the postconcussion process that should
      be followed, desires for better understanding of the guidelines by general
      practitioners (ie, medical doctors) who care for children with concussion, having
      more readily available information for parents and receiving more formal policy
      guiding timing of return-to-participation following concussion. Difficulties with
      the guidelines not addressing delayed presentations of concussion were also
      frequently mentioned. CONCLUSIONS: Parents are key stakeholders in concussion
      prevention and care in community sport. As such, their input should be considered
      when developing guidelines and resources for community sport. Furthermore,
      concussion information should be made available to parents in an easily
      accessible and community-friendly form.

PMID- 28761708
TI  - Vibrotactile feedback as a tool to improve motor learning and sports performance:
      a systematic review.
AB  - BACKGROUND: Evidence concerning the use of vibrotactile feedback for acquiring
      and learning new motor skills is limited. Although various concepts and
      applications for tactile feedback have been proposed, little is known about the
      suitability of this feedback mechanism in sports training. AIM: The goal of this
      systematic review was to gather knowledge on the efficacy of the use of
      vibrotactile feedback in improving sports performance skills. DESIGN: Systematic
      review. METHODS: Comprehensively searched databases were: PubMed, Cochrane and
      Web of Science. Studies investigating the effects of using vibrotactile feedback
      in sports training in healthy subjects were included in this review. RESULTS: No
      consensus was found regarding the positive effectiveness on performance using
      vibrotactile feedback in a sports context. No evidence was found that the
      addition of tactile feedback is effective for acquiring new motor skills. None of
      the studies show a significant learning effect.

PMID- 28761709
TI  - Effects of football sporting activity on renal and liver functions among young
      undergraduate students of a Nigerian tertiary institution.
AB  - BACKGROUND: Football sporting exercise is one of the most popular events in the
      world. While there are well-documented reports on the effects of different
      athletic sporting activities on the biochemical markers of renal and liver
      functions, there are paucity of well-documented reports on the effects of
      football activity on Nigerian sportsmen, hence the need for this study. METHOD:
      Biochemical markers of renal and liver functions (urea, creatinine, aspartate
      aminotransaminase (AST), alanine aminotransaminase (ALT), alkaline phosphatase
      (ALP)) were determined using Cobas c 111 auto-analyser by Roche. RESULTS: The
      mean urea (mmol/L)+/-SEM, creatinine (MUmol/L)+/-SEM, AST (U/L)+/-SEM, ALT
      (U/L)+/-SEM and ALP (U/L)+/-SEM values before and after soccer exercise were
      3.56+/-0.12, 3.76+/-0.13, p=0.000; 79.36+/-1.53, 95.90+/-2.03, p=0.000; 32.54+/
      1.15, 35.81+/-1.32, p=0.000; 15.68+/-1.02, 13.97+/-0.81, p=0.000; and 82.21+/
      3.67, 86.08+/-3.86, p=0.046, respectively. Pearson's degree of association for
      AST and ALT before and after exercise were r=0.678, p=0.000 and r=0.770, p=0.000,
      respectively; ALT and ALP before exercise showed a positive and significant
      association (r=0.317, p=0.028). On the other hand, there was a negative but
      insignificant correlation between urea before exercise and ALP after exercise (r=
      0.003, p=0.982) and urea before exercise versus AST after exercise (r=-0.120,
      p=0.418). A positive but insignificant association was observed between urea and
      creatinine before exercise (r=0.093, p=0.530). CONCLUSION: Football sporting
      event is associated with an increase in urea, creatinine, AST and ALP plasma
      values, and such interpretation of these parameters among sportsmen should be
      done with caution.

PMID- 28761710
TI  - Differential expression of alarmins-S100A9, IL-33, HMGB1 and HIF-1alpha in
      supraspinatus tendinopathy before and after treatment.
AB  - BACKGROUND: Alarmins, endogenous molecules released on tissue damage have been
      shown to play an important role in inflammatory musculoskeletal conditions
      including fracture repair andrheumatoid arthritis. However, the contribution of
      alarmins to the pathogenesis of tendon disease is not fully understood. METHODS:
      We investigated expression of alarmin proteins (S100A9, high-mobility group box 1
      (HMGB1) and interleukin-33 (IL-33) and hypoxia-inducible factor 1alpha (HIF
      1alpha), a subunit of an oxygen sensitive transcription factor, in three cohorts
      of human supraspinatus tissues: healthy (n=6), painful diseased (n=13) and post
      treatment pain-free tendon samples (n=5). Tissue samples were collected during
      shoulder stabilisation surgery (healthy) or by biopsy needle (diseased/treated).
      Immunohistochemistry was used to investigate the protein expression of these
      factors in these healthy, diseased and treated tendons. Kruskal-Wallis with
      pairwise post hoc Mann-Whitney U tests were used to test for differences in
      immunopositive staining between these tissue cohorts. Additionally, costaining
      was performed to identify the cell types expressing HIF-1alpha, S100A9, IL-33 and
      HMGB1 in diseased tendons. RESULTS: Immunostaining showed HIF-1alpha and S100A9
      were increased in diseased compared with healthy and post-treatment pain-free
      tendons (p<0.05). IL-33 was reduced in diseased compared with healthy tendons
      (p=0.0006). HMGB1 was increased in post-treatment pain-free compared with healthy
      and diseased tendons (p<0.01). Costaining of diseased tendon samples revealed
      that HIF-1alpha, S100A9 and IL-33 were expressed by CD68+ and CD68- cells,
      whereas HMGB1 was predominantly expressed by CD68- cells. CONCLUSIONS: This study
      provides insight into the pathways contributing to the progressionand resolution
      of tendon disease. We found potential pro-inflammatory and pathogenic roles for
      HIF-1alpha and S100A9, a protective role fornuclear IL-33 and a potentially
      reparative function for HMGB1 in diseased supraspinatus tendons.

PMID- 28761711
TI  - Comparison of two accelerometers for measuring physical activity and sedentary
      behaviour.
AB  - PURPOSE: A central aspect of physical activity and sedentary behaviour research
      is accurate exposure assessment in the context of disease outcomes. The primary
      objectives of this study were to evaluate the convergent validity and test-retest
      reliability of the ActiGraph GT3X+ and activPAL3 accelerometers. METHODS:
      Participants from the Breast Cancer and Exercise Trial in Alberta (n=266) wore
      both devices concurrently during waking hours for 7 days. Summary measures of
      time (hours/day) for physical activity and sedentary behaviour were compared
      between devices using Student's t-tests. Bland-Altman plots were used to assess
      or evaluate the mean differences and limits of agreement between monitors, and
      intraclass correlation coefficients (ICCs) were used to assess the test-retest
      reliability of two 7-day activity monitor administrations separated by 2 weeks
      (n=29). RESULTS: When comparing the ActiGraph Vector Magnitude (VM), which
      incorporates all three axes of movement (x, y, z), and the Vertical Axis (VT),
      which detects movement on the vertical or y-axis only, with the activPAL3, all
      measures of physical activity were statistically significantly different. The
      difference in measured time in sedentary behaviour was not statistically
      significant different when comparing the activPAL3 and ActiGraph (VT) estimates
      (p=0.47) but was statistically significant different for activPAL3 compared with
      ActiGraph (VM) (p<0.001). ICCs were high and consistent for each method across
      all behaviours, ranging from 0.87 to 0.93, with the exception of moderate
      activity and moderate-to-vigorous activity by the ActiGraph (VT) at 0.66 and
      0.67, respectively. CONCLUSION: Despite small mean differences and comparable
      recordings by both devices at the group level, the precision of estimates between
      methods was low with wide limits of agreement, suggesting these devices may not
      be used interchangeably for measuring physical activity and sedentary behaviour
      using common data reduction methods.

PMID- 28761712
TI  - Statistical testing of baseline differences in sports medicine RCTs: a systematic
      evaluation.
AB  - BACKGROUND/AIM: The CONSORT (Consolidated Standards of Reporting Trials)
      statement discourages reporting statistical tests of baseline differences between
      groups in randomised controlled trials (RCTs). However, this practice is still
      common in many medical fields. Our aim was to determine the prevalence of this
      practice in leading sports medicine journals. METHODS: We conducted a
      comprehensive search in Medline through PubMed to identify RCTs published in the
      years 2005 and 2015 from 10 high-impact sports medicine journals. Two reviewers
      independently confirmed the trial design and reached consensus on which articles
      contained statistical tests of baseline differences. RESULTS: Our search strategy
      identified a total of 324 RCTs, with 85 from the year 2005 and 239 from the year
      2015. Overall, 64.8% of studies (95% CI (59.6, 70.0)) reported statistical tests
      of baseline differences; broken down by year, this percentage was 67.1% in 2005
      (95% CI (57.1, 77.1)) and 64.0% in 2015 (95% CI (57.9, 70.1)). CONCLUSIONS:
      Although discouraged by the CONSORT statement, statistical testing of baseline
      differences remains highly prevalent in sports medicine RCTs. Statistical testing
      of baseline differences can mislead authors; for example, by failing to identify
      meaningful baseline differences in small studies. Journals that ask authors to
      follow the CONSORT statement guidelines should recognise that many manuscripts
      are ignoring the recommendation against statistical testing of baseline
      differences.

PMID- 28761713
TI  - The effect of 1 week of repeated ischaemic leg preconditioning on simulated
      Keirin cycling performance: a randomised trial.
AB  - BACKGROUND: Coaches continually seek new ways of doing things and also refine
      existing techniques to improve sporting performance. Coaches are currently
      experimenting using ischaemic preconditioning (IPC) over consecutive days in the
      hope of improving competitive performances. AIMS: First, to quantify the
      physiological impact of 1 week of IPC on simulated Keirin cycling performance.
      Second, to investigate if biochemical stress markers are affected over the
      treatment period. METHODS: Using a randomised, sham-controlled design, 18 active
      adults undertook seven consecutive days of IPC treatment (4*5 min
      occlusion/reperfusion) applied to each leg at either 220 mm Hg (treatment, n=9)
      or 20 mm Hg (sham, n=9). Urinary measures of inflammation, oxidative stress and
      indirect nitric oxide synthesis were undertaken daily. A simulated Keirin cycling
      competition (4*30 s Wingate tests) was performed on day 10, with baseline and
      postintervention cycling VO2max (days 1, 11 and 18) and 30 s Wingate tests (day
      2) undertaken for comparison. RESULTS: The treatment group had enhanced mean
      cycling power (3.4%), while neopterin and biopterin in conjunction with total
      neopterin were significantly lower (p<0.05) and total biopterin significantly
      greater (p<0.05) during the simulated Keirin. Aerobic fitness measures
      significantly improved from baseline to postintervention (VO2peak: 12.8% ?,
      maximal aerobic power: 18.5% ?). CONCLUSIONS: Seven consecutive days of IPC
      improved aerobic and anaerobic capacity measures, with modulations in oxidative
      stress, immune system activation and nitric oxide/catecholamine synthesis.

PMID- 28761714
TI  - Recruiting adult participants to physical activity intervention studies using
      sport: a systematic review.
AB  - OBJECTIVE: To undertake a systematic review of the effectiveness of recruitment
      mechanisms for engaging and retaining target participants in sports interventions
      to promote physical activity behaviour change in adults. DESIGN: A narrative
      systematic review of published studies providing details of the effectiveness of
      recruitment techniques used in interventions aimed at increasing physical
      activity via sport in adults. DATA SOURCES: Searches were conducted using five
      electronic databases, clinical trial registers, grey literature and snowballing
      from reference lists. All papers published in the English language were
      considered. The search was completed in November 2015. ELIGIBILITY CRITERIA: All
      articles providing information on the recruitment of adults into interventions
      involving sport and reporting physical activity or participation outcomes were
      included. RESULTS: Twenty-three studies met the inclusion criteria. The quality
      of recruitment reporting across included studies was generally classified as
      poor, lacking detailed descriptions of recruitment processes and providing
      insufficient reporting of recruitment outcomes. There was a distinct recruitment
      bias for more affluent, white, middle-aged women. Active-only recruitment
      techniques appeared to achieve a participant sample with more representative
      demographic characteristics than passive approaches. CONCLUSIONS: Due to
      inadequate reporting and evaluation, the mechanisms for achieving effective
      recruitment and engagement in sport, particularly in hard-to-reach groups, are
      still unclear. Independent of recruitment mode, creating an intervention and
      context that reflect the interests and motivations of the target audience
      presents a promising area. There is an urgent need for more robust evaluation
      design and reporting of sports interventions.

PMID- 28761715
TI  - Association between fasting insulin and high-sensitivity C reactive protein in
      Korean adults.
AB  - BACKGROUND: High-sensitivity C reactive protein (hs-CRP) is a reliable indicator
      of atherosclerotic diseases and is associated with hyperinsulinaemia. The purpose
      of this study is to examine the association between hs-CRP and fasting insulin
      levels in Korean adults not taking medication for hypertension, dyslipidaemia or
      diabetes, nor provided with specific dietary advice. METHODS: This cross
      sectional study included 2588 subjects who participated in the 2015 Korean
      National Health and Nutrition Examination Survey. High-risk hs-CRP was defined as
      hs-CRP>2 mg/L. Subjects were divided into four groups with fasting insulin (<5, 5
      10, 10-15,>15 uIU/mL). RESULTS: The mean hs-CRP in our sample was 1.22 mg/L. hs
      CRP was positively associated with fasting insulin level. The occurrence of high
      risk hs-CRP with increasing fasting insulin levels was 7.6%, 9.8%, 19.1% and
      28.2%, respectively. In comparing high-risk hs-CRP between the highest (>15
      uIU/mL) and lowest (<5 uIU/mL) insulin groups, the OR (95% CI) was 4.59 (2.77
      7.58). triglycerides/high-density lipoprotein ratio was also associated with hs
      CRP. Low-density lipoprotein cholesterol was not associated with hs-CRP.
      CONCLUSIONS: Higher level of fasting insulin is positively associated with high
      risk hs-CRP.

PMID- 28761716
TI  - Prevalence of laceration injuries in professional and amateur rugby union: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Studded footwear can cause severe lacerations in rugby union; the
      prevalence of these injuries is currently unknown. OBJECTIVE: To summarise the
      skin and laceration injury prevalence in published epidemiological studies and to
      investigate any differences in skin injury risk between amateur and professional
      players. DESIGN: Systematic literature review and meta-analysis of
      epidemiological studies. DATA SOURCES: PubMed, Web of Science, Scopus and Ovid.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective, epidemiological studies
      published in English after 1995, measuring a minimum of 400 match or 900 training
      exposure hours. Participants should be adult rugby union players (amateur or
      professional). The study should report a separate skin or laceration injury
      category and provide sufficient detail to calculate injury prevalence within this
      category. RESULTS: Twelve studies were included. Mean skin injury prevalence
      during matches was 2.4 injuries per 1000 exposure hours; during training
      sessions, the prevalence was 0.06 injuries per 1000 exposure hours. Skin injuries
      accounted for 5.3% of match injuries and 1.7% of training injuries. Skin injury
      risk was similar for amateur compared with professional players during matches
      (OR: 0.63, p=0.46.), but higher during training sessions (OR: 9.24, p=0.02).
      CONCLUSIONS: The skin injury prevalence of 2.4 injuries per 1000 exposure hours
      is equivalent to one time-loss injury sustained during matches per team, per
      season. Amateur players are more likely to sustain skin injuries during training
      sessions than professional players. There is a need for more studies observing
      injuries among amateur players. TRIAL REGISTRATION NUMBER: PROSPERO
      CRD42015024027.

PMID- 28761717
TI  - Physical activity during pregnancy and infant's birth weight: results from the 3D
      Birth Cohort.
AB  - AIM: To evaluate the association between maternal physical activity and infant's
      birth weight or risk of inappropriate weight for gestational age (GA), and
      whether this association differs by infant's sex, maternal body mass index (BMI)
      or pregnancy complications in a prospective cohort study. METHODS: 1913 pregnant
      women from the 3D Birth Cohort (Quebec, Canada) completed the Pregnancy Physical
      Activity Questionnaire at each trimester. Energy expenditure (metabolic
      equivalent of task (MET)*hours/week) for total activity, sports and exercise and
      vigorous intensity activities was calculated. The associations with birth weight
      and risk of inappropriate weight for GA were evaluated by regression modelling.
      Interactions were tested with infant's sex, maternal prepregnancy BMI,
      gestational diabetes, hypertensive disorders and prematurity. RESULTS: Each 1
      MET/hours/week increase in sports and exercise in the first trimester was
      associated with a 2.5 g reduction in infant's birth weight (95% CI -4.8 to -0.3)
      but was not associated with the risk of small weight for GA. In contrast,
      although not significant, a 17% reduction in the risk of large weight for GA was
      observed with increasing sports and exercise. Furthermore, in women with
      subsequent pre-eclampsia (but not normotensive or hypertensive women), each 1
      MET/hours/week increment spent in any vigorous exercise in the first trimester
      reduced the infant's birth weight by 19.8 g (95% CI -35.2 to -4.3). CONCLUSIONS:
      Pregnant women with higher sports and exercise levels in the first trimester
      delivered infants with a lower birth weight. The risk of reducing infant's birth
      weight with vigorous exercise in women who develop pre-eclampsia later in
      pregnancy requires evaluation.

PMID- 28761718
TI  - An observational study of spectators' step counts and reasons for attending a
      professional golf tournament in Scotland.
AB  - BACKGROUND: Spectators at several hundred golf tournaments on six continents
      worldwide may gain health-enhancing physical activity (HEPA) during their time at
      the event. This study aims to investigate spectators' reasons for attending and
      assess spectator physical activity (PA) (measured by step count). METHODS:
      Spectators at the Paul Lawrie Matchplay event in Scotland (August 2016) were
      invited to take part in this study. They were asked to complete a brief
      questionnaire with items to assess (1) demographics, (2) reasons for attendance
      and (3) baseline PA. In addition, participants were requested to wear a pedometer
      from time of entry to the venue until exit. RESULTS: A total of 339 spectators
      were recruited to the study and out of which 329 (97.2%) returned step-count
      data. Spectators took a mean of 11 589 steps (SD 4531). 'Fresh air' (rated median
      9 out of 10) then 'watching star players', 'exercise/physical activity', 'time
      with friends and family' and 'atmosphere' (all median 8 out of 10) were rated the
      most important reasons for attending. CONCLUSION: This study is the first to
      assess spectator physical activity while watching golf (measured by step count).
      Obtaining exercise/PA is rated as an important reason for attending a tournament
      by many golf spectators. Spectating at a golf tournament can provide HEPA. 82.9%
      of spectators achieved the recommended daily step count while spectating. Further
      research directly assessing whether spectating may constitute a 'teachable
      moment', for increasing physical activity beyond the tournament itself, is
      merited.

PMID- 28761719
TI  - Effect of a gluteal activation warm-up on explosive exercise performance.
AB  - OBJECTIVES: To evaluate the effect of a gluteal activation warm-up on the
      performance of an explosive exercise (the high hang pull (HHP)). METHODS:
      Seventeen professional rugby union players performed one set of three HHPs (with
      80% of their one repetition maximum load) following both a control and activation
      warm-up. Peak electrical activity of the gluteus maximus and medius was
      quantified using electromyography (EMG). In addition, the kinematics and kinetics
      of nine players was also recorded using force plate and motion capture
      technology. These data were analysed using a previously described musculoskeletal
      model of the right lower limb in order to provide estimates of the muscular force
      expressed during the movement. RESULTS: The mean peak EMG activity of the gluteus
      maximus was significantly lower following the activation warm-up as compared with
      the control (p<0.05, effect size d=0.30). There were no significant differences
      in the mean peak estimated forces in gluteus maximus and medius, the quadriceps
      or hamstrings (p=0.053), although there was a trend towards increased force in
      gluteus maximus and hamstrings following the activation warm-up. There were no
      differences between the ground reaction forces following the two warm-ups.
      CONCLUSION: This study suggests that a gluteal activation warm-up may facilitate
      recruitment of the gluteal musculature by potentiating the glutes in such a way
      that a smaller neural drive evokes the same or greater force production during
      movement. This could in turn potentially improve movement quality.

PMID- 28761720
TI  - Age-related changes in the effects of strength training on lower leg muscles in
      healthy individuals measured using MRI.
AB  - BACKGROUND: We previously measured the rate of regaining muscle strength during
      rehabilitation of lower leg muscles in patients following lower leg casting. Our
      primary aim in this study was to measure the rate of gain of strength in healthy
      individuals undergoing a similar training regime. Our secondary aim was to test
      the ability of MRI to provide a biomarker for muscle function. METHODS: Men and
      women were recruited in three age groups: 20-30, 50-65 and over 70 years. Their
      response to resistance training of the right lower leg twice a week for 8 weeks
      was monitored using a dynamometer and MRI of tibialis anterior, soleus and
      gastrocnemius muscles at 2 weekly intervals to measure muscle size (anatomical
      cross-sectional area (ACSA)) and quality (T2 relaxation). Forty-four volunteers
      completed the study. RESULTS: Baseline strength declined with age. Training had
      no effect in middle-aged females or in elderly men in dorsiflexion. Other groups
      significantly increased both plantarflexion and dorsiflexion strength at rates up
      to 5.5 N m week-1 in young females in plantarflexion and 1.25 N m week-1 in young
      males in dorsiflexion. No changes were observed in ACSA or T2 in any age group in
      any muscle. CONCLUSION: Exercise training improves muscle strength in males at
      all ages except the elderly in dorsiflexion. Responses in females were less clear
      with variation across age and muscle groups. These results were not reflected in
      simple MRI measures that do not, therefore, provide a good biomarker for muscle
      atrophy or the efficacy of rehabilitation.

PMID- 28761721
TI  - Preventing running-related injuries using evidence-based online advice: the
      design of a randomised-controlled trial.
AB  - INTRODUCTION: Running-related injuries (RRIs) are frequent and can lead to
      cessation of health promoting activities. Several risk factors for RRIs have been
      identified. However, no successful injury prevention programme has been developed
      so far. Therefore, the aim of the present study is to investigate the effect of
      an evidence-based online injury prevention programme on the number of RRIs.
      METHODS AND ANALYSIS: The INSPIRE trial is a randomised-controlled trial with a 3
      month follow-up. Both novice and more experienced runners, aged 18 years and
      older, who register for a running event (distances 5 km up to 42.195 km) will be
      asked to participate in this study. After completing the baseline questionnaire,
      participants will be randomised into either the intervention group or control
      group. Participants in the intervention group will get access to the online
      injury prevention programme. This prevention programme consists of information on
      evidence-based risk factors and advices to reduce the injury risk. The primary
      outcome measure is the number of self-reported RRIs in the time frame between
      registration for a running event and 1 month after the running event. Secondary
      outcome measures include the running days missed due to injuries, absence of work
      or school due to injuries, and the injury location. ETHICS AND DISSEMINATION: An
      exemption for a comprehensive application is obtained by the Medical Ethical
      Committee of the Erasmus University Medical Centre Rotterdam, Netherlands. The
      results of the study will be published in peer-reviewed journals and presented on
      international congresses. TRIAL REGISTRATION NUMBER: NTR5998. Pre-results.

PMID- 28761722
TI  - A TBX5 3'UTR variant increases the risk of congenital heart disease in the Han
      Chinese population.
AB  - TBX5 is a vital transcription factor involved in cardiac development in a dosage
      dependent manner. But little is known about the potential association of TBX5 3'
      untranslated region (UTR) variations with congenital cardiac malformations. This
      study aimed to investigate the relationship between TBX5 3'UTR variants and risk
      for congenital heart disease (CHD) susceptibility in two Han Chinese populations,
      and to reveal its molecular mechanism. The relationship between TBX5 3'UTR
      variants and CHD susceptibility was examined in 1 177 CHD patients and 990
      healthy controls in two independent case-control studies. Variant rs6489956 C>T
      was found to be associated with increased CHD susceptibility in both cohorts. The
      combined CHD risk for the CT and TT genotype carriers was 1.83 times higher than
      that of CC genotype, while the risk for CT or TT genotype was 1.94 times and 2.31
      times higher than that of CC carriers, respectively. Quantitative real-time PCR
      and western blot analysis showed that T allele carriers exhibited reduced TBX5
      mRNA and protein levels in CHDs tissues. Compared with C allele, T allele showed
      increased binding affinity to miR-9 and miR-30a in both luciferase assays and
      surface plasmon resonance analysis. Functional analysis confirmed that miR-9 and
      miR-30a downregulated TBX5 expression at the transcriptional and translational
      levels, respectively. The assays in zebrafish model were in support of the
      interaction of miR-9/30a and TBX5 3'UTR (C and T allele). We concluded that TBX5
      3'UTR variant rs6489956 increased susceptibility of CHD in the Han Chinese
      population because it changes the binding affinity of two target miRNAs that
      specifically mediate TBX5 expression.

PMID- 28761723
TI  - Indolent peritoneal mesothelioma: PI3K-mTOR inhibitors as a novel therapeutic
      strategy.
AB  - : Peritoneal mesothelioma (MPeM) is a scarce abdominal-pelvic malignancy that
      presents with non-specific features and exhibits a wide clinical spectrum from
      indolent to aggressive disease. Due to it being a rare entity, there is a lack of
      understanding of its molecular drivers. Most treatment data are from limited
      small studies or extrapolated from pleural mesothelioma. Standard treatment
      includes curative surgery or pemetrexed-platinum palliative chemotherapy. To
      date, the use of novel targeted agents has been disappointing. Described is the
      management of two young women with papillary peritoneal mesothelioma with
      widespread recurrence having received platinum-pemetrexed chemotherapy. Both
      patients obtained symptomatic and disease benefit with apitolisib, a dual
      phosphoinositide 3-kinase-mammalian target of rapamycin (PI3K-mTOR) inhibitor for
      subsequent relapses, with one patient having a partial response for almost 3
      years. Both are alive and well 10-13 years from diagnosis. CONCLUSION: These case
      presentations highlight a subgroup of rare MPeM that behave indolently that is
      compatible with long-term survival. This series identifies the use of targeted
      therapies with PI3K-mTOR-based inhibitors as a novel approach, warranting further
      clinical assessment. Development of prognostic biomarkers is essential to aid
      identify tumour aggressiveness, help stratify patients and facilitate treatment
      decisions.

PMID- 28761724
TI  - Time since start of first-line therapy as a predictive clinical marker for
      nintedanib in patients with previously treated non-small cell lung cancer.
AB  - INTRODUCTION: No predictive clinical or genetic markers have been identified or
      validated for antiangiogenic agents in lung cancer. We aimed to identify a
      predictive clinical marker of benefit for nintedanib, an angiokinase inhibitor,
      using data from two large second-line non-small cell lung cancer Phase III trials
      (LUME-Lung 1 ([LL1] and LUME-Lung 2). METHODS: Predictive marker identification
      was conducted in a multi-step process using data from both trials; a hypothesis
      was generated, confirmed and validated. Statistical analyses included a stepwise
      selection approach, a recursive partitioning method and the evaluation of HRs,
      including treatment-by-covariate interactions. The marker was finally validated
      using a prospectively defined hierarchical testing procedure and treatment-by
      covariate interaction for overall survival (OS) based on LL1. RESULTS: Time since
      start of first-line therapy (TSFLT) was identified as the only predictive
      clinical marker. A cut-off of 9 months was chosen for further analysis, based on
      HRs and recursive partitioning. The prospectively defined final validation using
      OS data from LL1 established the strong relationship between TSFLT and treatment
      with nintedanib. Patients with adenocarcinoma with TSFLT <9 months showed a
      greater survival benefit (median OS 10.9 vs 7.9 months, HR 0.75 [95% CI 0.60
      0.92]; p=0.0073) compared with patients in the TSFLT >9 months group (median OS
      17.0 vs 15.1 months, HR 0.89 [95% CI 0.66-1.19]). CONCLUSIONS: Patients with
      shorter TSFLT derive a greater progression-free survival and OS benefit from
      nintedanib. This clinical marker could be used for patient selection and further
      investigation is warranted regarding pathways promoting aggressive tumour growth
      and antiangiogenic tyrosine kinase inhibitor benefit.

PMID- 28761725
TI  - Impact of intervention aimed at improving the integration of oncology units and
      local palliative care services: results of the multicentre prospective sequential
      MIRTO study.
AB  - BACKGROUND: Chemotherapy (CT) in patients with advanced cancer (ACP) near the end
      of life is an increasing practice of oncology units. A closer integration with
      palliative care (PC) services could reduce the use of potentially harmful CT.
      This prospective study is aimed at assessing whether a more integrated care model
      could reduce CT use near the end of life and increase local PC service
      utilisation. METHODS: The study enrolled sequentially two cohorts of ACP with an
      estimated life expectancy of <=6 months. In the first cohort, the usual
      oncologist's practice to prescribe CT and to activate local PC services were
      recorded. In cohort 2, the oncologist's decision was taken after an in-hospital
      consultation with the local PC teams. After patient death, a follow-back survey
      was carried out. RESULTS: The two cohorts included 109 and 125 evaluable
      patients, respectively. The oncologist's decision to prescribe CT occurred in
      51.4% and 60%, respectively: the percentages of patients receiving the final CT
      administration in the last 30 days of life did not differ in the two cohorts
      (33.9% and 29.3%, respectively,p=0.83). Conversely, an increase in home PC
      service utilisation (from 56.9% to 82.4%, p=0.00), at home deaths (from 40.4% to
      56.8%, p=0.01) and in-hospice deaths (from 8.3% to 19.2%, p=0.00) occurred in
      cohort 2. CONCLUSION: The implementation of an initial in-hospital consultation
      of oncologists and experienced home PC teams has not reduced the use of CT near
      the end of life but increased PC service utilisation and reduced in-hospital
      deaths.

PMID- 28761726
TI  - Phase I study of neoadjuvant chemotherapy with S-1 and oxaliplatin for locally
      advanced gastric cancer (Neo G-SOX PI).
AB  - BACKGROUND: The prognosis of locally advanced gastric cancer, such as clinical T4
      disease, bulky nodal involvement, type 4 and large type 3 gastric cancer, remains
      unsatisfactory, even with D2 gastrectomy followed by adjuvant chemotherapy. One
      promising approach is neoadjuvant chemotherapy. Combination chemotherapy with S-1
      and oxaliplatin (SOX) is recognised as a potentially promising regimen for
      gastric cancer. However, the use of neoadjuvant chemotherapy consisting of SOX
      for locally advanced gastric cancer has not been reported. The aim of this study
      was to determine the maximum tolerated dose (MTD) and recommended dose of
      preoperative chemotherapy combined with SOX for locally advanced gastric cancer.
      METHODS: Patients received two cycles of neoadjuvant chemotherapy with
      oxaliplatin on day 1, as well as S-1 (80 mg/m2/day, twice daily) for 14 days,
      repeated every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph
      node dissection followed by adjuvant S-1 (80 mg/m2/day, twice daily) for 1 year.
      Escalation of oxaliplatin dose was planned (starting at level 0, oxaliplatin 100
      mg/m2; level 1, 130 mg/m2). RESULTS: Six patients were enrolled. MTD was not
      reached at level 1. Oxaliplatin 130 mg/m2 in combination with S-1 80 mg/m2/day
      twice daily could be administered with acceptable toxicity. Peripheral neuropathy
      was observed in all patients but with no functional disorders. No treatment
      related death was observed and the incidence of operative morbidity was
      tolerable. Resection with curative intent was undertaken in all patients with R0
      resection performed in five (83%) and R1 in one. Two of the six patients had a
      pathological complete response (33%). CONCLUSION: Neoadjuvant chemotherapy with
      an SOX regimen was feasible in patients with locally advanced gastric cancer. The
      recommended phase II dose was determined to be oxaliplatin 130 mg/m2 in
      combination with S-1 80 mg/m2/day, twice daily.

PMID- 28761727
TI  - S-1 and oxaliplatin (SOX) plus bevacizumab versus mFOLFOX6 plus bevacizumab as
      first-line treatment for patients with metastatic colorectal cancer: updated
      overall survival analyses of the open-label, non-inferiority, randomised phase
      III: SOFT study.
AB  - OBJECTIVE: The SOFT study previously demonstrated that S-1 and oxaliplatin (SOX)
      plus bevacizumab was non-inferior to l-leucovorin, fluorouracil and oxaliplatin
      (mFOLFOX6) plus bevacizumab in terms of the primary end point of progression-free
      survival (PFS) as first-line chemotherapy for metastatic colorectal cancer
      (mCRC). The overall survival (OS) data were immature at the time of the primary
      analysis. METHODS: A total of 512 patients were enrolled and randomly assigned to
      receive either mFOLFOX6 plus bevacizumab (5 mg/kg of bevacizumab, followed by 200
      mg/m2 of l-leucovorin given simultaneously with 85 mg/m2 of oxaliplatin, followed
      by a 400 mg/m2 bolus of 5-FU on day 1 and then 2400 mg/m2 of 5-FU as an
      intravenous infusion over the course of 46 hours, every 2 weeks) or SOX plus
      bevacizumab (7.5 mg/kg of bevacizumab, 130 mg/m2 of oxaliplatin on day 1 and 40
      60 mg of S-1 two times per day for 2 weeks, followed by a 1-week rest). The
      primary end point was PFS. After the primary analysis, the follow-up survey was
      cut-off on 30 September 2013, and the final OS data were analysed. RESULTS: With
      a median follow-up of 37.7 months, the median survival time (MST) was 29.7 months
      with mFOLFOX6 plus bevacizumab and 29.6 months with SOX plus bevacizumab (HR,
      1.018; 95% CI 0.823 to 1.258). Median PFS was 11.7 months in the mFOLFOX6 plus
      bevacizumab group and 12.2 months in the SOX plus bevacizumab group (HR, 1.051;
      95% CI 0.876 to 1.262; pnon-inferiority=0.0115). CONCLUSION: Our results
      reconfirmed that SOX plus bevacizumab is non-inferior to mFOLFOX6 plus
      bevacizumab in terms of PFS. MST did not differ between the groups. SOX plus
      bevacizumab is considered an effective regimen for first-line chemotherapy in
      patients with mCRC and can be used instead of mFOLFOX6 plus bevacizumab. TRIAL
      REGISTRATION NUMBER: JapicCTI-090699.

PMID- 28761728
TI  - Pemetrexed-cisplatin with concurrent thoracic radiation after pemetrexed
      cisplatin induction in patients with unresectable locally advanced non-squamous
      NSCLC: results by age subgroup.

PMID- 28761729
TI  - Peritumoural ground-glass opacity associated with tumour pseudoprogression in a
      patient with non-small cell lung cancer treated with nivolumab.
AB  - Nivolumab, a monoclonal antibody to programmed cell death protein-1 (PD-1), has
      revolutionised the management of patients with advanced non-small cell lung
      cancer (NSCLC). Treatment with nivolumab is associated with toxicities known as
      immune-related adverse events. Although pneumonitis is a potentially serious
      event, little is known of its clinical and radiographic features. We here report
      a case of NSCLC for which treatment with nivolumab resulted in the development of
      ground-glass opacity surrounding the primary lung tumour and an associated
      increase in tumour size. Administration of prednisone led to rapid resolution of
      both clinical symptoms and the abnormal shadow on the lung field as well as
      shrinkage of the tumour. However, retreatment with nivolumab induced clinical and
      radiographic manifestations similar to those triggered by the first challenge.
      Given the increasing use of PD-1 inhibitors in patients with NSCLC, further
      studies are warranted to provide a better understanding of this phenomenon.

PMID- 28761730
TI  - Management of metastatic colorectal cancer patients: guidelines of the Italian
      Medical Oncology Association (AIOM).
AB  - In the past 15 years, the outcome for patients with metastatic colorectal cancer
      has substantially improved owing to the availability of new cytotoxic and
      biological agents along with many significant advances in molecular selection,
      the use of personalised therapy and locoregional treatment, a more widespread
      sharing of specific professional experiences (multidisciplinary teams with
      oncologists, surgeons, radiotherapists, radiologists, biologists and
      pathologists), and the adoption of patient-centred healthcare strategies. The
      Italian Medical Oncology Association (AIOM) has developed evidence-based
      recommendations to help oncologists and all professionals involved in the
      management of patients with metastatic colorectal cancer in their daily clinical
      practice.

PMID- 28761732
TI  - The hard road to ranking the clinical benefit of antineoplastic agents: ESMO
      Award 2016 presentation.

PMID- 28761731
TI  - Health-related quality of life in a randomised phase III study of gemcitabine
      plus S-1, S-1 alone and gemcitabine alone for locally advanced or metastatic
      pancreatic cancer: GEST study.
AB  - OBJECTIVE: This study was performed to compare health-related quality of life
      (HRQOL) of gemcitabine plus S-1 (GS), S-1 alone and gemcitabine alone as first
      line chemotherapy for locally advanced or metastatic pancreatic cancer in the
      GEST (Gemcitabine and TS-1 Trial) study and to assess the impacts of adverse
      events and tumour response on HRQOL. METHODS: Patients were randomly assigned to
      receive gemcitabine alone (1000 mg/m2 weekly for 3 of 4 weeks), S-1 alone (80,
      100 or 120 mg/day twice daily for 4 of 6 weeks) or GS (gemcitabine at 1000 mg/m2
      weekly plus S-1 at 60, 80 or 100 mg/day twice daily for 2 of 3 weeks). HRQOL was
      assessed using the EuroQoL-5D (EQ-5D) questionnaire at baseline and weeks 6, 12,
      24, 48 and 72. EQ-5D scores, quality-adjusted life months (QALMs), quality
      adjusted progression-free months (QAPFMs) and time until definitive HRQOL
      deterioration (TUDD) were compared among the three groups. The impacts of adverse
      events and tumour response on EQ-5D scores were analysed. RESULTS: Including EQ
      5D scores after death as 0, the mean profile was significantly better in the GS
      than gemcitabine group (difference, 0.069; p=0.003), but not the S-1 group
      (difference, -0.011; p=0.613). The mean profiles until death were similar in the
      three groups. QALMs, QAPFMs and TUDD were significantly longer in the GS than
      gemcitabine group (p<0.001, p<0.001 and p=0.004, respectively), but not the S-1
      group (p=0.563, p=0.741 and p=0.701, respectively). Fatigue, anorexia and tumour
      response were significantly associated with changes in EQ-5D scores. CONCLUSIONS:
      GS achieved better HRQOL than gemcitabine alone, resulting a good balance between
      overall survival and HRQOL benefits. S-1 alone provides HRQOL similar to that
      provided by gemcitabine alone. Preventing fatigue and anorexia and maintaining
      better response would improve HRQOL.

PMID- 28761733
TI  - Prevalence of hypothyroidism among patients with breast cancer treated with
      radiation to the supraclavicular field: a single-centre survey.
AB  - PURPOSE: We investigated the prevalence of hypothyroidism (HT) in patients with
      breast cancer who received radiation therapy to the supraclavicular (SC) field to
      evaluate the effect of radiation on thyroid. METHODS: Between April 2007 and May
      2016, consecutive patients with invasive breast cancer who received SC radiation
      were recruited. Thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were
      measured between April and August 2016. On the basis of the radiation-planning CT
      images, thyroid volume was calculated and dose-volume parameters were estimated.
      The endpoints were the prevalence of HT as determined by high levels of TSH and
      low levels of fT4 in serum, and the prevalence of subclinical HT, determined by
      high-serum TSH and normal fT4. RESULTS: Among the 68 consecutive patients, 26
      were excluded from evaluation (10 patients died, 6 had a history of previous
      thyroid disease and 10 were lost to follow-up). One (2.4%) and six (14.3%) of
      these patients had HT and subclinical HT, respectively, with a mean TSH level of
      8.27 uU/mL. By univariate analysis, a predictive factor of HT and subclinical HT
      was a thyroid volume <8 cm3 (OR 6.44, 95% CI 1.14 to 36.6; p=0.043). Multivariate
      analysis also showed an association between thyroid volume <8 cm3 and HT or
      subclinical HT (OR 18.48, 95% CI 1.48 to 230.86; p=0.024). CONCLUSIONS: The
      prevalence of HT in patients with breast cancer studied was relatively low.
      Although thyroid volume appeared to be a predictive marker of HT in this cohort,
      further prospective evaluation is needed.

PMID- 28761734
TI  - Immune checkpoint inhibitors in lung cancer: the holy grail has not yet been
      found....

PMID- 28761735
TI  - Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated
      advanced lung adenocarcinoma.
AB  - OBJECTIVE: Oral tyrosine kinase inhibitor has been shown to prolong progression
      free survival (PFS) in estimated glomerular filtration rate (EGFR) mutation
      positive adenocarcinoma; however, the comparator arm has not included the current
      standard adenocarcinoma regimen (pemetrexed carboplatin induction followed by
      maintenance pemetrexed) and patients from Indian subcontinent. Hence, this study
      was carried out in Indian patients to compare gefitinib with the above-mentioned
      chemotherapy regimen. METHODS: This was an open-labelled, randomised, parallel
      group study comparing gefitinib (250 mg orally daily) with pemetrexed (500 mg/m2)
      and carboplatin (area under the curve 5) doublet intravenous induction
      chemotherapy regimen followed by maintenance pemetrexed (500 mg/m2) in patients
      with EGFR-activating mutation-positive stage IIIB or stage IV adenocarcinoma lung
      in the first-line setting. The primary endpoint for the study was PFS. 260
      patients were required to demonstrate a 50% improvement in PFS of gefitinib over
      chemotherapy, with 80% power and 5% type 1 error. With an expected 5% dropout
      rate, the sample size was 290 patients. RESULTS: The median PFS in gefitinib arm
      was 8.4 months (95% CI 6.3 to 10.5 months) compared with 5.6 months (95% CI 4.2
      to 7.0 months) in pemetrexed-carboplatin arm (HR: 95% CI 0.513 to 0.851; p 
      0.001). The impact of gefitinib on PFS was seen across all subgroups.There was no
      statistically significant difference in overall survival between the two arms.
      Haematologicalgrade3-4toxicities likeanaemia,neutropaenia and thrombocytopaenia
      were common in the pemetrexed-carboplatin arm while grade3-4 acneiform rash and
      diarrhoeawere common in the gefitinib arm. CONCLUSION: The study confirms the
      superiority of gefitinib in prolonging PFS against the most active chemotherapy
      regimen of pemetrexed-carboplatin followed by maintenance pemetrexed in EGFR
      mutated lung adenocarcinoma. The median PFS in Indian patients in gefitinib arm
      is similar to that reported in east Asians and Caucasians.

PMID- 28761736
TI  - Male breast cancer: finding the way in this uncommon path.

PMID- 28761737
TI  - In the literature: February 2017.

PMID- 28761738
TI  - Results of the safety run-in part of the METAL (METformin in Advanced Lung
      cancer) study: a multicentre, open-label phase I-II study of metformin with
      erlotinib in second-line therapy of patients with stage IV non-small-cell lung
      cancer.
AB  - PURPOSE: Our previous works demonstrated the ability of metformin to revert
      resistance to gefitinib, a selective epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild
      type (WT) cell lines. However, the optimal dose of metformin to be used in non
      diabetic patients still remains to be defined. The phase I-II trial METformin in
      Advanced Lung cancer (METAL) was designed to identify the maximum tolerated dose
      and to evaluate safety and activity of metformin combined with erlotinib in
      second-line treatment of patients with stage IV NSCLC, whose tumours harbour the
      WT EGFR gene. PATIENTS AND METHODS: We report results from the safety run-in part
      designed to detect acute toxicities, to study pharmacokinetics and to identify
      the recommended phase II dose (RPD) to be used for the following phase of the
      study. In the run-in phase, metformin treatment was administered according to a
      dose escalation scheme and, subsequently, combined with erlotinib. RESULTS:
      Twelve patients were enrolled. Common adverse events were diarrhoea, decreased
      appetite, abdominal pain, vomiting and skin toxicity, mostly reversible with
      symptomatic medical treatment. Dose-limiting toxicities were vomiting and
      diarrhoea registered in the initial cohort receiving metformin 2000 mg plus
      erlotinib at 150 mg die, which was declared the maximum administered dose. Only
      one of nine patients treated at the next lower dose of 1500 mg of metformin plus
      erlotinib at 150 mg experienced G3 gastrointestinal toxicity. Metformin plasma
      concentration profile confirmed the trend already observed in non-diabetic
      population. Glycemic profiles showed stability of the blood glucose level within
      the physiological range for non-diabetic subjects. At a follow-up of 30 weeks,
      six (50%) patients experienced a disease control (5 SD and 1 partial response).
      CONCLUSIONS: The RP2D of metformin dose was defined at 1500 mg/day to be combined
      with erlotinib 150 mg. TRIAL REGISTRATION NUMBER: EudraCT number: 2014-000349-59.

PMID- 28761739
TI  - The effect of adjuvant chemotherapy in male breast cancer: 134 cases from a
      retrospective study.
AB  - BACKGROUND: Male breast cancer (BC) is a kind of rare tumour. There were few
      researches concerning the effect of chemotherapy for it. The purpose of this
      study is to estimate the value of chemotherapy on prognosis in male BC. PATIENTS
      AND METHODS: Complete clinical and pathological information of male BC were
      collected from January 1990 to January 2008 in Zhejiang Cancer Hospital in China.
      134 cases of male BC were included for analysis and separated into two groups
      based on receiving chemotherapy or not receiving chemotherapy. The disease-free
      survival (DFS) and overall survival (OS) between chemotherapy group and non
      chemotherapy group were compared with Kaplan-Meier survival curve. Stratified
      analysis was used to evaluate the strength of the association between
      chemotherapy and each risk factor. Multivariate analysis was conducted by using
      COX proportional hazard regression model. RESULTS: There were 58.21% (78/134)
      cases who underwent chemotherapy and 41.79% (56/134) cases without chemotherapy.
      There were 20 cases (25.64%) with recurrence/metastasis in patients with
      chemotherapy and six cases (10.71%) in patients without chemotherapy. The mean
      DFS time of male BC with chemotherapy and non-chemotherapy is 150.87 and 154.13
      months, respectively (chi2=3.825, p=0.050). The mean OS time of male BC with
      chemotherapy and non-chemotherapy is 155.33 and 154.26 months, respectively
      (chi2=2.542, p=0.111). COX proportional hazard regression model showed that the
      two groups had similar DFS (HR=0.386, p=0.165), while chemotherapy might be a
      protective fact on OS (HR=0.140, p=0.026). CONCLUSION: The utility of
      chemotherapy should be considered in the high risk level of recurrence/metastasis
      in male BC.

PMID- 28761740
TI  - Patient-reported tolerability of adverse events in phase 1 trials.
AB  - BACKGROUND: Phase I experts recommend revisiting dose-limiting toxicity (DLT)
      definition to include chronic and cumulative toxicities induced by new
      molecularly targeted therapies. Patient's assessment of late toxicities'
      tolerability is, however, unknown. MATERIALS AND METHODS: A prospective survey on
      adverse events (AEs) tolerability on 23 National Cancer InstituteCommon
      Terminology Criteria for Adverse Event, Version 4 (NCI-CTCAE.v4) items was
      conducted at Gustave Roussy's Phase I department. Patients' maximum tolerability
      duration was recorded at baseline, during trial and at trial completion. Results
      were compared with the corresponding physicians' survey. RESULTS: 52 patients
      enrolled in 27 Phase I trials between May 2014 and November 2015 completed 102
      forms. At baseline, the most feared G2/G3 AEs were haematuria (74%), vomiting
      (71%) and hyperglycemia (64%)/dry mouth (94%), hyperglycemia (92%) and vomiting
      (92%). At trial completion, the most feared G2/G3 AEs were personality change
      (83.3%), haematuria (82%) and fever (80%)/dry mouth, fever and dizziness (100%
      each). Tolerability score did not differ over time. More previous treatments and
      occurrence of severe AEs were associated with better tolerability at study
      completion (p=0.0234 and p=0.0153, respectively, in multivariate analysis).
      Patient's tolerability differed from physician's assessment. CONCLUSION: AEs
      considered intolerable by patients are toxicities that directly impact their
      quality of life and differ from those feared by physicians or included in DLT
      definition. Patient-reported tolerability of AEs may help in optimising drug
      development.

PMID- 28761741
TI  - Tumour-infiltrating lymphocytes are correlated with higher expression levels of
      PD-1 and PD-L1 in early breast cancer.
AB  - BACKGROUND: The presence of tumour-infiltrating lymphocytes (TILs) is a
      favourable prognostic factor in patients with early breast cancer. Programmed
      cell death-1 (PD-1) and its ligand PD-L1 are associated with a variety of adverse
      features. The purpose of this study was to clarify the relationships between
      TILs, PD-1 and PD-L1 as well as their prognostic implications in early breast
      cancer. METHODS: We investigated 180 patients with breast cancer who received
      neoadjuvant chemotherapy and underwent subsequent surgery for stage II-III
      invasive breast carcinoma between 1999 and 2007. TIL expression was classified as
      low or high using a previously reported scoring model. PD-1 and PD-L1 expression
      levels were determined by immunohistochemistry. The correlation between PD-1
      expression in TILs and PD-L1 expression in cancer cells was also investigated.
      RESULTS: Higher tumour grade was significantly correlated with PD-L1 expression
      in tumours (p<0.0001). PD-1 and PD-L1 expression levels were associated with
      tumour subtype and were highest in triple-negative tumours (p<0.0001).
      Furthermore, expression of each of PD-1 and PD-L1 was significantly correlated
      with higher TIL expression and pathological complete response (pCR) (p<0.0001).
      PD-L1 expression in cancer cells was significantly correlated with PD-1
      expression in TILs (p=0.03). The correlations between pCR and expression of each
      of PD-L1 and PD-1 were not significant. CONCLUSION: Expression of PD-L1 and PD-1
      in early breast cancer is associated with higher TIL scores and pCR; conversely,
      expression of these proteins correlates with poor prognostic clinicopathological
      factors such as tumour grade and subtype. TILs, PD-1 and PD-L1 can potentially
      predict the response to treatment.

PMID- 28761742
TI  - Implementing precision cancer medicine in the public health services of Norway:
      the diagnostic infrastructure and a cost estimate.
AB  - OBJECTIVE: Through the conduct of an individual-based intervention study, the
      main purpose of this project was to build and evaluate the required
      infrastructure that may enable routine practice of precision cancer medicine in
      the public health services of Norway, including modelling of costs. METHODS: An
      eligible patient had end-stage metastatic disease from a solid tumour. Metastatic
      tissue was analysed by DNA sequencing, using a 50-gene panel and a study
      generated pipeline for analysis of sequence data, supplemented with fluorescence
      in situ hybridisation to cover relevant biomarkers. Cost estimations compared
      best supportive care, biomarker-agnostic treatment with a molecularly targeted
      agent and biomarker-based treatment with such a drug. These included costs for
      medication, outpatient clinic visits, admission from adverse events and the
      biomarker-based procedures. RESULTS: The diagnostic procedures, which comprised
      sampling of metastatic tissue, mutation analysis and data interpretation at the
      Molecular Tumor Board before integration with clinical data at the Clinical Tumor
      Board, were completed in median 18 (8-39) days for the 22 study patients. The 23
      invasive procedures (12 from liver, 6 from lung, 5 from other sites) caused a
      single adverse event (pneumothorax). Per patient, 0-5 mutations were detected in
      metastatic tumours; however, no actionable target case was identified for the
      current single-agent therapy approach. Based on the cost modelling, the biomarker
      based approach was 2.5-fold more costly than best supportive care and 2.5-fold
      less costly than the biomarker-agnostic option. CONCLUSIONS: The first project
      phase established a comprehensive diagnostic infrastructure for precision cancer
      medicine, which enabled expedite and safe mutation profiling of metastatic
      tumours and data interpretation at multidisciplinary tumour boards for patients
      with end-stage cancer. Furthermore, it prepared for protocol amendments, recently
      approved by the designated authorities for the second study phase, allowing more
      comprehensive mutation analysis and opportunities to define therapy targets.

PMID- 28761743
TI  - Checkpoint inhibitors in the treatment of urological malignancies.
AB  - Checkpoint inhibitors are monoclonal antibodies attach to several different
      receptors on T-cells or tumour cells expressing receptors for cytotoxic T
      lymphocyte antigen 4 (CTLA-4), programmed death-1 (PD-1) and their ligand (PD
      L1). Since 2010, numerous trials on different tumour types have been conducted,
      which was resulted in these drugs being approved for the treatment of melanoma,
      lung cancer, Hodgkin's lymphoma and head and neck cancers. Urological cancers,
      especially urothelial and renal-cell carcinomas, are immunogenic tumours. Since
      the late 70s, the bacillus Calmette-Gurin (BCG) vaccine has been used for
      intravesical instillation in non-muscle invasive bladder cancer from the mid-90s
      up until the discovery of tyrosine kinase inhibitors (TKIs) in 2007, interleukin
      2 (IL-2) and interferon alpha (IFNalpha), which were the standard of care for
      metastatic renal-cell cancer. Two checkpoint inhibitors are already approved by
      the Food and Drug Administration: atezolizumab for metastatic urothelial cancer
      and nivolumab for metastatic renal-cell carcinoma. There are many drugs are in
      different phases of clinical development. Here we review the current status of
      checkpoint inhibitors in the treatment of urological tumours.

PMID- 28761744
TI  - Discussing and prescribing expensive unfunded anticancer drugs in Australia.
AB  - OBJECTIVE: Australia has a publicly funded universal healthcare system which
      heavily subsidises the cost of most registered anticancer drugs. The use of
      anticancer drugs that are unfunded, that is, not subsidised by the government,
      entails substantial out-of-pocket costs for patients. We sought to determine how
      frequently Australian medical oncologists discuss and prescribe unfunded
      anticancer drugs, and their attitudes and beliefs about their use. METHODS:
      Members of the Medical Oncology Group of Australia (MOGA) completed an online
      survey about their clinical practices over a recent 3-month period. A negative
      binomial regression model was used to examine the influence of respondent
      characteristics on the rate of discussions about, and prescription of, unfunded
      anticancer drugs. RESULTS: Of the 154 respondents (27% of 575 MOGA members), 92%
      had discussed and 68% had prescribed at least one unfunded anticancer drug in the
      last 3 months. Respondents reported discussing unfunded anticancer drugs with an
      average of 2.5 patients per month (95% CI 2.1 to 2.9), and prescribed them to an
      average of 0.9 patients per month (95% CI 0.7 to 1.2). The rate of discussing
      unfunded anticancer drugs was associated with being fully qualified (p=0.01), and
      being in a metropolitan practice (p=0.009), the rate of prescription was
      associated only with being in metropolitan practice (p=0.006). The concerns about
      discussing and prescribing unfunded anticancer drugs rated most important were as
      follows: 'potential to cause financial hardship' and 'difficulty for patients to
      evaluate the benefits versus the costs'. CONCLUSIONS: Australian medical
      oncologists frequently discuss and prescribe unfunded anticancer drugs, and are
      concerned about their patients having to face difficult decisions and financial
      hardship. Further research is needed to better understand the factors that affect
      how oncologists and patients value expensive, unfunded anticancer drugs.

PMID- 28761746
TI  - Clinical value of early detection of circulating tumour DNA-BRAFV600mut in
      patients with metastatic melanoma treated with a BRAF inhibitor.

PMID- 28761745
TI  - Multiple primary tumours: challenges and approaches, a review.
AB  - When in a patient more than one tumour in the same or a different organ is
      diagnosed, multiple primary tumours may be present. For epidemiological studies,
      different definitions of multiple primaries are used with the two main
      definitions coming from the project Surveillance Epidemiology and End Results and
      the International Association of Cancer Registries and International Agency for
      Research on Cancer. The differences in the two definitions have to be taken into
      consideration when reports on multiple primaries are analysed. In this review,
      the literature on multiple primaries is reviewed and summarised. Overall, the
      frequency of multiple primaries is reported in the range of 2-17%. Aetiological
      factors that may predispose patients to multiple primaries can be grouped into
      host related, lifestyle factors and environmental influences. Some of the most
      common cancer predisposition syndromes based on a clinical presentation are
      discussed and the relevant genetic evaluation and testing are characterised.
      Importantly, from a clinical standpoint, clinical situations when multiple
      primaries should be suspected and ruled out in a patient are discussed.
      Furthermore, general principles and possible treatment strategies for patients
      with synchronous and metachronous multiple primary tumours are highlighted.

PMID- 28761747
TI  - Eribulin for metastatic breast cancer (MBC) treatment: a retrospective,
      multicenter study based in Campania, south Italy (Eri-001 trial).
AB  - BACKGROUND: On the basis of the results of two pivotal phase III clinical trials,
      eribulin mesylate is currently approved in EU for the treatment of advanced
      breast cancer (aBC) in patients who have previously received an anthracycline and
      a taxane in either the adjuvant or the metastatic setting, and at least one
      chemotherapeutic regimen for metastatic disease. METHODS: In our study, we
      investigated the efficacy and tolerability of eribulin as second or further line
      chemotherapy in 137 women affected by aBC. RESULTS: Eribulin as monotherapy
      provided benefit in terms of progression-free survival (PFS), response rate (RR)
      and disease control rate (DCR) independently of its use as second or late-line
      therapy. The overall RR and DCR were 17.5% and 64%, respectively. In particular,
      DCR and overall RR were 50% and 13.6%, 65.4% and 21.1%, 70.4% and 14.8% and 66.7%
      and 16.7% in second, third, fourth and further lines of treatment, respectively.
      Median PFS (mPFS) according to the line of therapy was 5.7, 6.3, 4.5 and 4.0
      months in patients treated with eribulin in second, third, fourth and over the
      fourth line, respectively. No significant difference in terms of mPFS was found
      between the various BC subtypes. Overall, eribulin resulted safe and most adverse
      events were of grade 1 or 2 and easily manageable. Grades 3-4 toxicities were
      neutropaenia and neurotoxicity. CONCLUSIONS: With the limitations due to the
      observational nature of our findings, eribulin was shown to be an effective and
      safe therapeutic option in heavily pretreated patients with aBC.

PMID- 28761748
TI  - New treatment options for metastatic renal cell carcinoma.
AB  - During the last decade, the treatment of advanced or metastatic renal cell
      carcinoma (RCC) was revolutionised with the advent of antiangiogenic drugs and
      tyrosine-kinase inhibitors. Several agents targeting the vascular endothelial
      growth factor (VEGF) pathway (sunitinib, bevacizumab, pazopanib, axitinib) or the
      mammalian target of rapamycin pathway (temsirolimus, everolimus) were since then
      progressively approved for first-line or later-line use in the treatment of
      patients with advanced RCC and became the new standard of care. As a result, the
      survival of patients with advanced RCC has significantly improved from a median
      overall survival of approximately 12 months in the cytokines era to more than 26
      months with first-line VEGF inhibitors. During the two last years, the treatment
      of advanced RCC has witnessed a second revolution with the advent of immune
      checkpoint inhibitors, especially agents targeting the programmed cell death-1
      receptor, as well as with the advent of new generation tyrosine-kinase receptor
      inhibitors. This article will review the new therapeutic options available for
      the treatment of advanced RCC, as well as the future potential molecular targets
      that are currently being investigated.

PMID- 28761751
TI  - In the literature: April 2017.

PMID- 28761750
TI  - European Medicines Agency approval summary: Zaltrap for the treatment of patients
      with oxaliplatin-resistant metastatic colorectal cancer.
AB  - On 1 February 2013, a marketing authorisation valid throughout the European Union
      was issued for aflibercept (Zaltrap) in combination with irinotecan/5
      fluorouracil/folinic acid chemotherapy for the treatment of adults with
      metastatic colorectal cancer resistant to or progressive after an oxaliplatin
      containing regimen. Aflibercept is a recombinant fusion protein which blocks the
      activation of vascular endothelial growth factor (VEGF) receptors and the
      proliferation of endothelial cells, acting as a soluble decoy receptor that binds
      to VEGF-A with higher affinity than its native receptors, as well as placental
      growth factor and VEGF-B. The use of aflibercept was studied in a randomised,
      double-blind, placebo-controlled phase III study, in patients with metastatic
      colorectal cancer (mCRC) who had previously been treated with an oxaliplatin
      based treatment with or without prior bevacizumab. Aflibercept (n=612) was
      compared with placebo (n=614), both in combination with FOLFIRI (infusional
      fluorouracil, leucovorin and irinotecan). The primary endpoint of the study was
      overall survival (OS). The median OS in the intent-to-treat population was 13.5
      months in subjects treated with aflibercept compared with 12.1 months for
      subjects in the control arm (stratified HR=0.817, 95% CI 0.714 to 0.935,
      stratified pvalue=0.0032). The frequency of adverse events was higher in the
      aflibercept arm compared with the placebo arm, reflecting the toxicity profile of
      anti-VEGF agents in combination with chemotherapy. This paper is based on the
      scientific review of the application leading to approval of aflibercept in the
      EU. The detailed scientific assessment report and product information for this
      product are available on the European Medicines Agency website
      (http://www.ema.europa.eu). Trial registration number NCT00561470, Results.

PMID- 28761749
TI  - Antithrombotic therapy for prophylaxis and treatment of venous thromboembolism in
      patients with cancer: review of the literature on current practice and emerging
      options.
AB  - The treatment of cancer-associated venous thromboembolism (VTE) is difficult
      because cancer patients with VTE on anticoagulation are at an increased risk of
      bleeding compared with patients without VTE. This review summarises the evidence
      supporting the current standard of care and emerging treatment options. In
      difficult-to-treat subpopulations, where clinical data are often lacking, this
      review also provides the best clinical practice strategies based on the available
      data. The use of therapeutic doses of parenteral anticoagulants in patients with
      cancer-associated VTE for at least 3 to 6 months is supported by the current
      clinical data. After major cancer surgery, extended thromboprophylaxis for
      approximately 1 month following hospital discharge is also supported. In select
      populations of ambulatory cancer patients with solid tumours, or in patients with
      myeloma receiving immunomodulatory agents in combination with chemotherapy and/or
      corticosteroids, pharmacological prophylaxis could be considered. Although
      parenteral anticoagulants may not be tolerated by some patients, the data
      pertaining to the use of direct oral anticoagulants (DOACs) in cancer patients
      with VTE at this point can only be considered hypothesis generating. Clarity of
      the use of DOACs is awaiting the results of head-to-head trials between DOACs and
      parenteral anticoagulants. In addition, because of the lack of clinical trials,
      there are still unanswered questions on the optimal treatment regimens in
      subpopulations at increased risk of bleeding, including cancer patients with
      thrombocytopenia and those with brain metastases. For clinicians to balance the
      risk of recurrent thrombosis with the chance of bleeding, they need to assess the
      relevant clinical data. Current data support the use of parenteral anticoagulants
      in cancer patients with VTE, but many unanswered questions pertaining to the
      optimal regimens in special subpopulations and regarding the efficacy and safety
      of DOACs remain. To address this need, there are currently several clinical
      trials under way.

PMID- 28761752
TI  - CECOG educational illustrations: the blood-brain barrier and its relevance for
      targeted cancer therapies and immuno-oncology.
AB  - The blood-brain barrier (BBB) protects the central nervous system (CNS) from
      potentially harmful substances and molecules by limiting their influx from the
      blood stream into the brain parenchyma. Understanding the structure and
      functioning of the BBB is of major importance for the development of effective
      medical treatments for primary and secondary brain tumours. Therefore, we provide
      here a concise and illustrated educational description of the anatomy and
      physiology of the BBB and current concepts on its role for targeted cancer
      therapies and immuno-oncology.

PMID- 28761753
TI  - ESMO Copenhagen 2016: a lung cancer 'grand cru'.

PMID- 28761754
TI  - A new era of oncology through artificial intelligence.

PMID- 28761755
TI  - Where do they come from? A call for complete transparency regarding the origin of
      human tissues in research.

PMID- 28761756
TI  - New horizon in breast cancer therapy: highlights from the European Society for
      Medical Oncology.

PMID- 28761757
TI  - Mechanisms of action and rationale for the use of checkpoint inhibitors in
      cancer.
AB  - The large family of costimulatory molecules plays a crucial role in regulation of
      the immune response. These molecules modulate TCR signalling via phosphorylation
      cascades. Some of the coinhibitory members of this family, such as PD-1 and CTLA
      4, already constitute approved targets in cancer therapy and, since 2011, have
      opened a new area of antitumour immunotherapy. Many antibodies targeting other
      inhibitory receptors (Tim-3, VISTA, Lag-3 and so on) or activating costimulatory
      molecules (OX40, GITR and so on) are under evaluation. These antibodies have
      multiple mechanisms of action. At the cellular level, these antibodies restore
      the activation signalling pathway and reprogram T cell metabolism. Tumour cells
      become resistant to apoptosis when an intracellular PD-L1 signalling is blocked.
      CD8+ T cells are considered to be the main effectors of the blockade of
      inhibitory receptors. Certain CD8+ T cell subsets, such as non-hyperexhausted
      (CD28+, T-bethigh, PD-1int), follicular-like (CXCR-5+) or resident memory CD8+ T
      cells, are more prone to be reactivated by anti-PD-1/PD-L1 monoclonal antibody
      (mAb). In the future, the challenge will be to rationally combine drugs able to
      make the tumour microenvironment more permissive to immunotherapy in order to
      potentiate its clinical activity.

PMID- 28761758
TI  - The European Society for Medical Oncology 'Magnitude of Clinical Benefit Scale'
      field-tested in infrequent tumour entities: an extended analysis of its
      feasibility at the Medical University of Vienna.
AB  - BACKGROUND: The European Society for Medical Oncology Magnitude of Clinical
      Benefit Scale (ESMO-MCBS) is a new tool to quantify the clinical benefit that may
      be anticipated from a novel anticancer treatment. We present here an analysis on
      the feasibility of the ESMO-MCBS in less frequent tumour entities. METHODS: This
      study evaluates the practicability of the ESMO-MCBS for metastatic neuroendocrine
      tumours (NETs), soft tissue sarcomas, glioblastoma, thyroid cancer, pancreatic
      cancer, head/neck cancer, urothelial cancer and ovarian cancer at the Medical
      University Vienna. A three-step approach including data acquisition, assessment
      of ESMO-MCBS scores and evaluation of results with a focus on clinical
      feasibility was applied. RESULTS: In NET and thyroid cancer, all analysed trials
      were very comparable in design and efficacy, and the ESMO-MCBS scores appeared to
      be consistent with the clinical benefit seen in practice. For pancreatic cancer,
      it was more difficult to compare first-line trials due to diverging populations
      included in the respective studies. Concerning soft tissue sarcomas, the ESMO
      MCBS was applicable for gastrointestinal stromal tumours(GIST) and 'non-GIST'
      soft tissue sarcoma with respect to data deriving from randomised studies.
      However, due to the heterogeneity of the disease itself and a limited number of
      controlled trials, limitations are noted. In ovarian cancer, the ESMO-MCBS
      supported the use of bevacizumab in high-risk patients. To date, there are only
      limited data for glioblastoma, head/neck cancer and urothelial cancer but
      whenever randomised trials were available, the ESMO-MCBS rating supported
      clinical decisions. Interestingly, nivolumab for salvage treatment of head/neck
      cancer rated extremely high. CONCLUSION: The ESMO-MCBS scores supported our
      common treatment strategies and highlight the potential of new immunomodulatory
      drugs. Our results encourage further development of the ESMO-MCBS.

PMID- 28761759
TI  - Retrospective analysis of HER2 therapy interruption in patients responding to the
      treatment in metastatic HER2+ breast cancer.
AB  - INTRODUCTION: Human epidermal growth factor receptor 2 (HER2)-targeted-therapy
      regimens can lead to prolonged tumour responses in metastatic HER2+ breast
      cancer. Clinical trials have concerned use of HER2-targeted agents until disease
      progression, but it is unknown whether the therapy can be interrupted in cases of
      a good response. METHODS: Single institute, retrospective collection of data on
      patients with HER2+ metastatic breast cancer (n=68) was carried out through a
      pharmacy search for patients who had received trastuzumab in 2006-2014. Clinical
      and pathological factors, treatment history and survival data were collected from
      patient records. RESULTS: Median survival in metastatic disease (all patients)
      was 32 months and survival times were dramatically different in patients with and
      without trastuzumab as adjuvant or primary metastatic disease (median 16, 77 and
      35 months, respectively; p=0.0004). More importantly, HER2 therapy was
      intentionally interrupted in 21 responding patients, and these patients
      experienced long HER2-therapy-free intervals (median 51 months), with excellent
      long-term survival. A lack of previous adjuvant trastuzumab was the only
      statistically significant factor predictive of HER2 therapy interruption.
      CONCLUSIONS: These results from our retrospective study show that HER2 therapy
      interruption in patients with metastatic HER2+ breast cancer, who have responded
      to the therapy, is associated with low risk of rapid disease progression. Study
      suggests that therapy interruption in cases of response and reinitiation in
      progression is feasible.

PMID- 28761760
TI  - ASCO: practice changing studies in gastrointestinal cancer.

PMID- 28761761
TI  - Panretinal Photocoagulation Using Short-Pulse Laser Induces Less Inflammation and
      Macular Thickening in Patients with Diabetic Retinopathy.
AB  - We compared the effect of panretinal photocoagulation (PRP) using short-pulse
      laser (SPL) and conventional laser, regardless of the number of spots, in terms
      of their effect on the progression of diabetic macular edema (DME) and anterior
      flare intensity (AFI) in patients with high-risk nonproliferative diabetic
      retinopathy (non-PDR). Forty-two eyes of 42 patients were subjected to PRP using
      the conventional argon laser (Conv group) or SPL (SPL group). CRT and AFI levels
      in the SPL group were significantly lower than those in the Conv group (CRT at 4,
      6, and 10 weeks; AFI at 6, 10, and 18 weeks). Eyes of rabbits were
      photocoagulated using conventional laser with 500 spots (Conv 500s), SPL with 500
      spots (SPL 500s), or 1000 spots (SPL 1000s). Vascular endothelial growth factor
      (VEGF), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and
      monocyte chemotactic protein-1 (MCP-1) levels in vitreous humor were measured
      using an immunoassay. Compared to conventional laser, VEGF, IL-6, and MCP-1
      levels were significantly lower in the SPL 1000s and SPL 500s groups. In patients
      with high-risk non-PDR, SPL has a greater preventive effect on the progression of
      DME and AFI and produces less inflammatory cytokines than conventional lasers.

PMID- 28761762
TI  - Parafoveal OCT Angiography Features in Diabetic Patients without Clinical
      Diabetic Retinopathy: A Qualitative and Quantitative Analysis.
AB  - PURPOSE: To evaluate the capacity of OCT angiography (OCTA) for detecting
      infraclinical lesions in parafoveal capillaries in diabetic patients without
      diabetic retinopathy (DR). METHODS: This prospective observational cross
      sectional case-control study analyzed the superficial and deep capillary plexuses
      (SCP and DCP) on macular OCTA scans (3 * 3 mm) centered on the fovea. We compared
      22 diabetic patients (34 eyes included) without DR diagnosis on color fundus
      photographs, with 22 age- and gender-matched nondiabetic controls (40 eyes
      included). Qualitative analysis concerned morphological ischemic capillary
      alterations. Quantitative analysis measured foveal avascular zone (FAZ) size,
      parafoveal capillary density, and enlargement coefficient of FAZ between SCP and
      DCP. RESULTS: Neither the qualitative nor quantitative parameters were
      significantly different between both groups. No microaneurysms or venous
      tortuosity was observed in any of the analyzed images. On the SCP, the mean FAZ
      area was 0.322 +/- 0.125 mm2 in diabetic patients and 0.285 +/- 0.150 mm2 in
      controls, P = 0.31. On the DCP, the mean FAZ area was 0.444 +/- 0.153 mm2 in
      cases and 0.398 +/- 0.138 mm2 in controls, P = 0.20. CONCLUSION: OCTA did not
      detect infraclinical qualitative or quantitative differences in parafoveal
      capillaries of diabetic patients without DR in comparison with nondiabetic
      controls.

PMID- 28761763
TI  - Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia.
AB  - Valvular heart disease frequently occurs as a consequence of premature
      atherosclerosis in individuals with familial hypercholesterolemia (FH). Studies
      have primarily focused on aortic valve calcification in heterozygous FH, but
      there is paucity of data on the incidence of valvular disease in homozygous FH.
      We performed echocardiographic studies in 33 relatively young patients (mean age:
      26 years) with homozygous FH (mean LDL of 447 mg/dL, 73% on LDL apheresis) to
      look for subclinical valvulopathy. Twenty-one patients had evidence of
      valvulopathy of the aortic or mitral valves, while seven subjects showed notable
      mitral regurgitation. Older patients were more likely to have aortic valve
      calcification (>21 versus <=21 years: 59% versus 12.5%; p = 0.01) despite lower
      LDL levels at the time of the study (385 versus 513 mg/dL; p = 0.016). Patients
      with valvulopathy were older and had comparable LDL levels and a lower carotid
      intima-media thickness. Our data suggests that, in homozygous FH patients,
      valvulopathy (1) is present across a wide age spectrum and LDL levels and (2) is
      less likely to be influenced by lipid-lowering treatment. Echocardiographic
      studies that focused on aortic root thickening and stenosis and regurgitation are
      thus likely an effective modality for serial follow-up of subclinical valvular
      heart disease.

PMID- 28761764
TI  - Resurgence of Polymyxin B for MDR/XDR Gram-Negative Infections: An Overview of
      Current Evidence.
AB  - Polymyxin B has resurged in recent years as a last resort therapy for Gram
      negative multidrug-resistant (MDR) and extremely drug resistant (XDR) infections.
      Understanding newer evidence on polymyxin B is necessary to guide clinical
      decision making. Here, we present a literature review of polymyxin B in Gram
      negative infections with update on its pharmacology.

PMID- 28761765
TI  - Endoscopic Stenting as Bridge to Surgery versus Emergency Resection for Left
      Sided Malignant Colorectal Obstruction: An Updated Meta-Analysis.
AB  - INTRODUCTION: Emergency resection represents the traditional treatment for left
      sided malignant obstruction. However, the placement of self-expanding metallic
      stents and delayed surgery has been proposed as an alternative approach. The aim
      of the current meta-analysis was to review the available evidence, with
      particular interest for the short-term outcomes, including a recent multicentre
      RCT. METHODS: We considered randomized controlled trials comparing stenting as a
      bridge to surgery and emergency surgery for the management of left-sided
      malignant large bowel obstruction, performing a systematic review in MEDLINE,
      PubMed database, and the Cochrane libraries. RESULTS: We initially identified a
      total of 2543 studies. After the elimination of duplicates and the screening of
      titles and abstracts, seven studies, for a total of 448 patients, were
      considered. The current meta-analysis revealed no difference in the mortality
      rate between the stent group and the emergency surgery group; the postoperative
      complication rate (37.84% versus 54.87%, P = 0.02), the stoma rate (28.8% versus
      46.02%, P < 0.0001), and the incidence of wound infection (8.11% versus 15.49%, P
      = 0.01) were reduced after stent as a bridge to surgery. CONCLUSION: Colonic
      stenting as a bridge to surgery appears to be a safe approach to malignant large
      bowel obstruction. Possible advantages of this treatment can be identified in a
      reduced incidence of postoperative complications and a lower stoma rate. Further
      RCTs considering long-term outcomes and cost-effectiveness analysis are needed.

PMID- 28761766
TI  - Technical Details of Laparoscopic Sleeve Gastrectomy Leading to Lowered Leak
      Rate: Discussion of 1070 Consecutive Cases.
AB  - INTRODUCTION: Laparoscopic sleeve gastrectomy is a widely utilized and effective
      surgical procedure for dramatic weight loss in obese patients. Leak at the sleeve
      staple line is the most serious complication of this procedure, occurring in 1-3%
      of cases. Techniques to minimize the risk of sleeve gastrectomy leaks have been
      published although no universally agreed upon set of techniques exists. This
      report describes a single-surgeon experience with an approach to sleeve leak
      prevention resulting in a progressive decrease in leak rate over 5 years.
      METHODS: 1070 consecutive sleeve gastrectomy cases between 2012 and 2016 were
      reviewed retrospectively. Patient characteristics, sleeve leaks, and percent body
      weight loss at 6 months were reported for each year. Conceptual and technical
      changes aimed towards leak reduction are presented. RESULTS: With the
      implementation of the described techniques of the sleeve gastrectomy, the rate of
      sleeve leaks fell from 4% in 2012 to 0% in 2015 and 2016 without a significant
      change in weight loss, as depicted by 6-month change in body weight and percent
      excess BMI lost. CONCLUSION: In this single-surgeon experience, sleeve
      gastrectomy leak rate has fallen to 0% since the implementation of specific
      technical modifications in the procedure.

PMID- 28761767
TI  - Investigating the Evidence of Behavioral, Cognitive, and Psychiatric
      Endophenotypes in Autism: A Systematic Review.
AB  - Substantial evidence indicates that parents of autistic individuals often display
      milder forms of autistic traits referred to as the broader autism phenotype
      (BAP). To determine if discrete endophenotypes of autism can be identified, we
      reviewed the literature to assess the evidence of behavioral, cognitive, and
      psychiatric profiles of the BAP. A systematic review was conducted using EMBASE,
      MEDLINE, PsycINFO, PsycEXTRA, and Global Health. Sixty papers met our inclusion
      criteria and results are discussed according to the proportion of studies that
      yield significant deficits per domain. The behavioral, cognitive, and psychiatric
      endophenotypes in parents of autistic probands are still not clarified; however,
      evidence suggests mild social/communication deficits, rigid/aloof personality
      traits, and pragmatic language difficulties as the most useful sociobehavioral
      candidate endophenotype traits. The existence of deficits in the cognitive domain
      does suggest familial vulnerability for autism. Furthermore, increased depressed
      mood and anxiety can also be useful markers; however, findings should be
      interpreted with caution because of the small number of studies in such
      heterogeneously broad domains and several methodological limitations.

PMID- 28761769
TI  - Tacrolimus-Induced Type IV Renal Tubular Acidosis following Liver
      Transplantation.
AB  - Calcineurin inhibitors remain an integral component of immunosuppressive therapy
      regimens following solid organ transplantation. Although nephrotoxicity
      associated with these agents is well documented, type IV renal tubular acidosis
      is a rare and potentially underreported complication following liver
      transplantation. Hepatologists must be able to recognize this adverse effect as
      it can lead to fatal hyperkalemia. We describe a case of tacrolimus-induced
      hyperkalemic type IV renal tubular acidosis in a patient following an orthotopic
      liver transplant for alcoholic cirrhosis.

PMID- 28761768
TI  - Incidental Discovery of Multiorgan Extramedullary Plasmacytomas in the Setting of
      Newly Diagnosed Multiple Myeloma and Delayed Hemolytic Transfusion Reaction.
AB  - Extramedullary plasmacytomas (EMPs) are defined by the presence of clonal plasma
      cell proliferation outside of the bone marrow, portending an overall poor
      prognosis. This case highlights extramedullary plasmacytomas as an unusual
      presenting manifestation of multiple myeloma. Through incidental discovery during
      a delayed hemolytic transfusion reaction workup, EMPs were found in the liver,
      spleen, and possibly the lung. Though rare at presentation, this case emphasizes
      that the presence of EMPs should be considered at the outset as it not only
      impacts the treatment regimen for such patients but also considerably affects
      prognosis.

PMID- 28761770
TI  - Extended Peritoneal Dialysis and Renal Recovery in HIV-Infected Patients with
      Prolonged AKI: A Report of 2 Cases.
AB  - Peritoneal dialysis (PD) has recently been established as a treatment option for
      renal replacement therapy (RRT) in patients with acute kidney injury (AKI). Its
      efficacy in providing fluid and small solute removal has also been demonstrated
      in clinical trials and is equivalent to hemodialysis (HD). However, effect of RRT
      modality on renal recovery after AKI remains a controversy. Moreover, the setting
      of human immunodeficiency virus- (HIV-) infected patients with AKI requiring RRT
      makes the decision on RRT initiation and modality selection more complicated. The
      authors report here 2 cases of HIV-infected patients presenting with severe AKI
      requiring protracted course of acute RRT. PD had been performed uneventfully in
      both cases for 4-9 months before partial renal recovery occurred. Both patients
      eventually became dialysis independent but were left in chronic kidney disease
      (CKD) stage 4. These cases highlight the example of renal recovery even after a
      prolonged course of dialysis dependence. Thus, PD might be a suitable option for
      HIV patients with protracted AKI.

PMID- 28761771
TI  - Lateral Subtalar Dislocation with Tarsometatarsal Dislocation: A Case Report of a
      Rare Injury.
AB  - Dislocation of the fourth and fifth tarsometatarsal joints in conjunction with
      lateral subtalar dislocation is a rare occurrence. Little is known about the
      mechanism of injury, the appropriate treatment for this condition, and its
      ultimate prognosis. In this report, we describe this atypical presentation in a
      middle aged, otherwise healthy male who sustained a trivial twisting injury to
      the ankle when he slipped and fell on ice. Open reduction and K-wire fixation
      were necessary to affix the lateral tarsometatarsal and talonavicular joints. At
      one year postoperatively, he was able to return to his preinjury occupation with
      mild to moderate pain with prolonged walking. His Foot and Ankle Disability Index
      and American Orthopaedic Foot and Ankle Society scores were 64 and 65 points,
      respectively. Surgical intervention resulted in a stable plantigrade foot;
      however, the patient had early radiographic evidence of posttraumatic arthritis
      in the midfoot joints at one-year follow-up.

PMID- 28761772
TI  - A Rare Case of Aortoatrial Fistula from Streptococcal Endocarditis.
AB  - We represent an unfortunate case of postinfluenza streptococcal endocarditis in a
      34-year-old healthy male. He presented with hypoxic respiratory failure and was
      found to have mitral and aortic valve vegetation. Hospital course was complicated
      by the presence of an aortoatrial fistula from an aortic root abscess, persistent
      septic shock, and multiorgan failure.

PMID- 28761774
TI  - Proinflammatory and Anabolic Gene Expression Effects of Platelet-Rich Gel
      Supernatants on Equine Synovial Membrane Explants Challenged with
      Lipopolysaccharide.
AB  - Platelet-rich plasma (PRP) preparations are used in horses with osteoarthritis
      (OA). However, some controversies remain regarding the ideal concentration of
      platelets and leukocytes to produce an adequate anti-inflammatory and anabolic
      response in the synovial membrane. The aims of this study were to study the
      influence of leukoconcentrated platelet-rich gel (Lc-PRG) and leukoreduced
      platelet-rich gel (Lr-PRG) supernatants on the quantitative expression of some
      proinflammatory and anabolic genes in equine synovial membrane explants (SMEs)
      challenged with lipopolysaccharide (LPS). SMEs from six horses were cultured over
      96 h. Then, SMEs were harvested for RNA extraction and quantitative gene
      expression analysis by RT-qPCR for nuclear factor kappa B (NFkappaB), matrix
      metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with
      thrombospondin motifs 4 (ADAMTS-4), collagen type I alpha 1 (COL1A1), collagen
      type II alpha 1 (COL2A1), and cartilage oligomeric matrix protein (COMP). The 25%
      and 50% Lc-PRG supernatants led to downregulation of NFkappaB, MMP-13, ADAMTS-4,
      COL1A1, COL2A1, and COMP in SMEs. Lr-PRG supernatants (particularly at the 50%
      concentration) induced downregulation of NFkappaB, MMP-13, ADAMTS-4, and COL1A1
      and upregulation of COL2A1 and COMP. Lr-PRG supernatants should be used for the
      treatment of inflammatory arthropathies in horses because they have anti
      inflammatory and anabolic effects in the synovial membrane.

PMID- 28761773
TI  - Deep Brain Stimulation in Parkinson's Disease: New and Emerging Targets for
      Refractory Motor and Nonmotor Symptoms.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative condition
      characterized by bradykinesia, tremor, rigidity, and postural instability (PI),
      in addition to numerous nonmotor manifestations. Many pharmacological therapies
      now exist to successfully treat PD motor symptoms; however, as the disease
      progresses, it often becomes challenging to treat with medications alone. Deep
      brain stimulation (DBS) has become a crucial player in PD treatment, particularly
      for patients who have disabling motor complications from medical treatment. Well
      established DBS targets include the subthalamic nucleus (STN), the globus
      pallidus pars interna (GPi), and to a lesser degree the ventral intermediate
      nucleus (VIM) of the thalamus. Studies of alternative DBS targets for PD are
      ongoing, the majority of which have shown some clinical benefit; however, more
      carefully designed and controlled studies are needed. In the present review, we
      discuss the role of these new and emerging DBS targets in treating refractory
      axial motor symptoms and other motor and nonmotor symptoms (NMS).

PMID- 28761776
TI  - Primary productivity as a control over soil microbial diversity along
      environmental gradients in a polar desert ecosystem.
AB  - Primary production is the fundamental source of energy to foodwebs and
      ecosystems, and is thus an important constraint on soil communities. This
      coupling is particularly evident in polar terrestrial ecosystems where biological
      diversity and activity is tightly constrained by edaphic gradients of
      productivity (e.g., soil moisture, organic carbon availability) and geochemical
      severity (e.g., pH, electrical conductivity). In the McMurdo Dry Valleys of
      Antarctica, environmental gradients determine numerous properties of soil
      communities and yet relatively few estimates of gross or net primary productivity
      (GPP, NPP) exist for this region. Here we describe a survey utilizing pulse
      amplitude modulation (PAM) fluorometry to estimate rates of GPP across a broad
      environmental gradient along with belowground microbial diversity and
      decomposition. PAM estimates of GPP ranged from an average of 0.27 MUmol O2/m2/s
      in the most arid soils to an average of 6.97 MUmol O2/m2/s in the most productive
      soils, the latter equivalent to 217 g C/m2/y in annual NPP assuming a 60 day
      growing season. A diversity index of four carbon-acquiring enzyme activities also
      increased with soil productivity, suggesting that the diversity of organic
      substrates in mesic environments may be an additional driver of microbial
      diversity. Overall, soil productivity was a stronger predictor of microbial
      diversity and enzymatic activity than any estimate of geochemical severity. These
      results highlight the fundamental role of environmental gradients to control
      community diversity and the dynamics of ecosystem-scale carbon pools in arid
      systems.

PMID- 28761775
TI  - Real-time monitoring of superoxide anion radical generation in response to
      wounding: electrochemical study.
AB  - BACKGROUND: The growth and development of plants is deleteriously affected by
      various biotic and abiotic stress factors. Wounding in plants is caused by
      exposure to environmental stress, mechanical stress, and via herbivory.
      Typically, oxidative burst in response to wounding is associated with the
      formation of reactive oxygen species, such as the superoxide anion radical (O2*
      ), hydrogen peroxide (H2O2) and singlet oxygen; however, few experimental studies
      have provided direct evidence of their detection in plants. Detection of O2*-
      formation in plant tissues have been performed using various techniques including
      electron paramagnetic resonance spin-trap spectroscopy, epinephrine-adrenochrome
      acceptor methods, staining with dyes such as tetrazolium dye and nitro blue
      tetrazolium (NBT); however, kinetic measurements have not been performed. In the
      current study, we provide evidence of O2*- generation and its kinetics in the
      leaves of spinach (Spinacia oleracea) subjected to wounding. METHODS: Real-time
      monitoring of O2*- generation was performed using catalytic amperometry. Changes
      in oxidation current for O2*- was monitored using polymeric iron-porphyrin-based
      modified carbon electrodes (phi = 1 mm) as working electrode with Ag/AgCl as the
      reference electrode. RESULT: The results obtained show continuous generation of
      O2*- for minutes after wounding, followed by a decline. The exogenous addition of
      superoxide dismutase, which is known to dismutate O2*- to H2O2, significantly
      suppressed the oxidation current. CONCLUSION: Catalytic amperometric measurements
      were performed using polymeric iron-porphyrin based modified carbon electrode. We
      claim it to be a useful tool and a direct method for real-time monitoring and
      precise detection of O2*- in biological samples, with the potential for wide
      application in plant research for specific and sensitive detection of O2*-.

PMID- 28761777
TI  - Antimicrobial activities of widely consumed herbal teas, alone or in combination
      with antibiotics: an in vitro study.
AB  - BACKGROUND: Because of increasing antibiotic resistance, herbal teas are the most
      popular natural alternatives for the treatment of infectious diseases, and are
      currently gaining more importance. We examined the antimicrobial activities of 31
      herbal teas both alone and in combination with antibiotics or antifungals against
      some standard and clinical isolates of Pseudomonas aeruginosa, Acinetobacter
      baumannii, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis,
      methicillin susceptible/resistant Staphylococcus aureus and Candida albicans.
      METHODS: The antimicrobial activities of the teas were determined by using the
      disk diffusion and microbroth dilution methods, and the combination studies were
      examined by using the microbroth checkerboard and the time killing curve methods.
      RESULTS: Rosehip, rosehip bag, pomegranate blossom, thyme, wormwood, mint,
      echinacea bag, cinnamon, black, and green teas were active against most of the
      studied microorganisms. In the combination studies, we characterized all the
      expected effects (synergistic, additive, and antagonistic) between the teas and
      the antimicrobials. While synergy was observed more frequently between
      ampicillin, ampicillin-sulbactam, or nystatine, and the various tea combinations,
      most of the effects between the ciprofloxacin, erythromycin, cefuroxime, or
      amikacin and various tea combinations, particularly rosehip, rosehip bag, and
      pomegranate blossom teas, were antagonistic. The results of the time kill curve
      analyses showed that none of the herbal teas were bactericidal in their usage
      concentrations; however, in combination with antibiotics they showed some
      bactericidal effect. DISCUSSION: Some herbal teas, particularly rosehip and
      pomegranate blossom should be avoided because of their antagonistic interactions
      with some antibiotics during the course of antibiotic treatment or they should be
      consumed alone for their antimicrobial activities.

PMID- 28761778
TI  - Association between host species choice and morphological characters of main
      sensory structures of Culicoides in the Palaeartic region.
AB  - Culicoides (Diptera: Ceratopogonidae) serve as vectors of several mammalian and
      avian diseases, including bluetongue, Schmallenberg, African horse sickness,
      avian malaria and Oropouche. Host preference investigations are necessary to
      assess the transmission routes of vector-borne diseases and to inform mitigation
      strategies. A recent study examining the main sensory structures (palps and
      antennae) of Culicoides species suggests that they be classified as ornithophilic
      or mammalophilic according to their feeding habits. We analyzed Culicoides host
      preferences according to the literature and carried out a multiple correspondence
      analysis linking these preferences with morphological data. Seven out of 12
      variables were found to be reliable predictors of host preference in Culicoides
      species: Antenna Flagellomer-Sensilla Coeloconica-Number: (7-10) and (11-13);
      Antenna Flagellomer-Sensilla Coeloconica IV-X: presence; Palpus-size: wide and/or
      narrow opening and shallow pit; Palpus-Shape: strongly swollen; Antenna-Short
      sensilla trichodea-distal part segment IV to X-Number: 2 seta each. Our results
      demonstrate that the presence of sensilla coeloconica and the maxillary palpus
      can be used to separate ornithophilic and mammalophilic or
      ornithophilic/mammalophilic species.

PMID- 28761779
TI  - Identification of ecogeographical gaps in the Spanish Aegilops collections with
      potential tolerance to drought and salinity.
AB  - Drought, one of the most important abiotic stress factors limiting biomass,
      significantly reduces crop productivity. Salinization also affects the
      productivity of both irrigated and rain-fed wheat crops. Species of genus
      Aegilops can be considered crop wild relatives (CWR) of wheat and have been
      widely used as gene sources in wheat breeding, especially in providing resistance
      to pests and diseases. Five species (Ae. biuncialis, Ae. geniculata, Ae.
      neglecta, Ae. triuncialis and Ae. ventricosa) are included in the Spanish
      National Inventory of CWRs. This study aimed to identify ecogeographic gaps in
      the Spanish Network on Plant Genetic Resources for Food and Agriculture (PGRFA)
      with potential tolerance to drought and salinity. Data on the Spanish populations
      of the target species collected and conserved in genebanks of the Spanish Network
      on PGRFA and data on other population occurrences in Spain were compiled and
      assessed for their geo-referencing quality. The records with the best geo
      referencing quality values were used to identify the ecogeographical variables
      that might be important for Aegilops distribution in Spain. These variables were
      then used to produce ecogeographic land characterization maps for each species,
      allowing us to identify populations from low and non-represented ecogeographical
      categories in ex situ collections. Predictive characterization strategy was used
      to identify 45 Aegilops populations in these ecogeographical gaps with potential
      tolerance to drought and salinity conditions. Further efforts are being made to
      collect and evaluate these populations.

PMID- 28761781
TI  - The difference in expression of long noncoding RNAs in rat semen induced by high
      fat diet was associated with metabolic pathways.
AB  - BACKGROUND: Obesity, a common metabolic disease, is a known cause of male
      infertility due to its associated health risk. Long noncoding RNAs (lncRNAs) have
      also been reported to be associated with male reproductive diseases; however,
      their role in the association between high-fat diet-induced obesity (DIO) and
      male reproduction remains unclear. METHODS: We used microarray analysis to
      compare the expression levels of lncRNAs and mRNAs in the spermatozoa of rats
      with DIO and normal rats. We selected a few lncRNAs that were obviously up
      regulated or down-regulated, and then used RT-PCR to verify the accuracy of their
      expression. We then performed a functional enrichment analysis of the
      differentially expressed mRNAs using gene ontology and pathway analysis. Finally,
      target gene predictive analysis was used to explore the relationship between
      lncRNAs and mRNAs. RESULTS: The results revealed a statistically significant
      difference in the fasting blood glucose level in rats with DIO and control rats.
      We found that 973 lncRNAs and 2,994 mRNAs were differentially expressed in the
      sperm samples of the DIO rats, compared to the controls. GO enrichment analysis
      revealed 263 biological process terms, 39 cellular component terms, and 40
      molecular function terms (p < 0.01) in the differentially expressed mRNAs. The
      pathway analysis showed that metabolic pathways were most enriched in protein
      coding genes. DISCUSSION: To the best of our knowledge, this is the first report
      to show differences in the expression levels of lncRNAs and mRNAs in the sperms
      of rats with DIO and normal rats, and to determine the expression profile of
      lncRNAs in the sperm of rats with DIO. Our results have revealed a number of
      lncRNAs and pathways associated with obesity-induced infertility, including
      metabolic pathways. These pathways could be new candidates that help cope with
      and investigate the mechanisms behind the progression of obesity-induced male
      infertility.

PMID- 28761780
TI  - DNA-barcoding of forensically important blow flies (Diptera: Calliphoridae) in
      the Caribbean Region.
AB  - Correct identification of forensically important insects, such as flies in the
      family Calliphoridae, is a crucial step for them to be used as evidence in legal
      investigations. Traditional identification based on morphology has been
      effective, but has some limitations when it comes to identifying immature stages
      of certain species. DNA-barcoding, using COI, has demonstrated potential for
      rapid and accurate identification of Calliphoridae, however, this gene does not
      reliably distinguish among some recently diverged species, raising questions
      about its use for delimitation of species of forensic importance. To facilitate
      DNA based identification of Calliphoridae in the Caribbean we developed a
      vouchered reference collection from across the region, and a DNA sequence
      database, and further added the nuclear ITS2 as a second marker to increase
      accuracy of identification through barcoding. We morphologically identified
      freshly collected specimens, did phylogenetic analyses and employed several
      species delimitation methods for a total of 468 individuals representing 19
      described species. Our results show that combination of COI + ITS2 genes yields
      more accurate identification and diagnoses, and better agreement with
      morphological data, than the mitochondrial barcodes alone. All of our results
      from independent and concatenated trees and most of the species delimitation
      methods yield considerably higher diversity estimates than the distance based
      approach and morphology. Molecular data support at least 24 distinct clades
      within Calliphoridae in this study, recovering substantial geographic variation
      for Lucilia eximia, Lucilia retroversa, Lucilia rica and Chloroprocta idioidea,
      probably indicating several cryptic species. In sum, our study demonstrates the
      importance of employing a second nuclear marker for barcoding analyses and
      species delimitation of calliphorids, and the power of molecular data in
      combination with a complete reference database to enable identification of
      taxonomically and geographically diverse insects of forensic importance.

PMID- 28761782
TI  - Targeted NGS for species level phylogenomics: "made to measure" or "one size fits
      all"?
AB  - Targeted high-throughput sequencing using hybrid-enrichment offers a promising
      source of data for inferring multiple, meaningfully resolved, independent gene
      trees suitable to address challenging phylogenetic problems in species complexes
      and rapid radiations. The targets in question can either be adopted directly from
      more or less universal tools, or custom made for particular clades at
      considerably greater effort. We applied custom made scripts to select sets of
      homologous sequence markers from transcriptome and WGS data for use in the
      flowering plant genus Erica (Ericaceae). We compared the resulting targets to
      those that would be selected both using different available tools (Hyb-Seq;
      MarkerMiner), and when optimising for broader clades of more distantly related
      taxa (Ericales; eudicots). Approaches comparing more divergent genomes (including
      MarkerMiner, irrespective of input data) delivered fewer and shorter potential
      markers than those targeted for Erica. The latter may nevertheless be effective
      for sequence capture across the wider family Ericaceae. We tested the targets
      delivered by our scripts by obtaining an empirical dataset. The resulting
      sequence variation was lower than that of standard nuclear ribosomal markers
      (that in Erica fail to deliver a well resolved gene tree), confirming the
      importance of maximising the lengths of individual markers. We conclude that
      rather than searching for "one size fits all" universal markers, we should
      improve and make more accessible the tools necessary for developing "made to
      measure" ones.

PMID- 28761784
TI  - The influence of mortality and socioeconomic status on risk and delayed rewards:
      a replication with British participants.
AB  - Here, we report three attempts to replicate a finding from an influential
      psychological study (Griskevicius et al., 2011b). The original study found
      interactions between childhood SES and experimental mortality-priming condition
      in predicting risk acceptance and delay discounting outcomes. The original study
      used US student samples. We used British university students (replication 1) and
      British online samples (replications 2 and 3) with a modified version of the
      original priming material, which was tailored to make it more credible to a
      British audience. We did not replicate the interaction between childhood SES and
      mortality-priming condition in any of our three experiments. The only consistent
      trend of note was an interaction between sex and priming condition for delay
      discounting. We note that psychological priming effects are considered fragile
      and often fail to replicate. Our failure to replicate the original finding could
      be due to demographic differences in study participants, alterations made to the
      prime, or other study limitations. However, it is also possible that the
      previously reported interaction is not a robust or generalizable finding.

PMID- 28761783
TI  - Quantitative real-time PCR analysis of Anopheles dirus TEP1 and NOS during
      Plasmodium berghei infection, using three reference genes.
AB  - Quantitative reverse transcription PCR (qRT-PCR) has been an integral part of
      characterizing the immunity of Anopheles mosquitoes towards Plasmodium invasion.
      Two anti-Plasmodium factors of Anopheles, thioester-containing protein 1 (TEP1)
      and nitric oxide synthase (NOS), play a role in the refractoriness of Anopheles
      towards Plasmodium infection and are generally expressed during infection.
      However, these are less studied in Anopheles dirus, a dominant malaria vector in
      Southeast Asia. Furthermore, most studies used a single reference gene for
      normalization during gene expression analysis without proper validation. This may
      lead to erroneous quantification of expression levels. Therefore, the present
      study characterized and investigated the expression profiles of TEP1 and NOS of
      Anopheles dirus during P. berghei infection. Prior to that, the elongation factor
      1-alpha (EF1), actin 1 (Act) and ribosomal protein S7 (S7) genes were validated
      for their suitability as a set of reference genes. TEP1 and NOS expressions in
      An. dirus were found to be significantly induced after P. berghei infection.

PMID- 28761785
TI  - Taxonomic evaluation of selected Ganoderma species and database sequence
      validation.
AB  - Species in the genus Ganoderma include several ecologically important and
      pathogenic fungal species whose medicinal and economic value is substantial. Due
      to the highly similar morphological features within the Ganoderma, identification
      of species has relied heavily on DNA sequencing using BLAST searches, which are
      only reliable if the GenBank submissions are accurately labeled. In this study,
      we examined 113 specimens collected from 1969 to 2016 from various regions in
      Korea using morphological features and multigene analysis (internal transcribed
      spacer, translation elongation factor 1-alpha, and the second largest subunit of
      RNA polymerase II). These specimens were identified as four Ganoderma species: G.
      sichuanense, G. cf. adspersum, G. cf. applanatum, and G. cf. gibbosum. With the
      exception of G. sichuanense, these species were difficult to distinguish based
      solely on morphological features. However, phylogenetic analysis at three
      different loci yielded concordant phylogenetic information, and supported the
      four species distinctions with high bootstrap support. A survey of over 600
      Ganoderma sequences available on GenBank revealed that 65% of sequences were
      either misidentified or ambiguously labeled. Here, we suggest corrected
      annotations for GenBank sequences based on our phylogenetic validation and
      provide updated global distribution patterns for these Ganoderma species.

PMID- 28761786
TI  - The bivalve Thyasira cf. gouldi hosts chemoautotrophic symbiont populations with
      strain level diversity.
AB  - Invertebrates from various marine habitats form nutritional symbioses with
      chemosynthetic bacteria. In chemosynthetic symbioses, both the mode of symbiont
      transmission and the site of bacterial housing can affect the composition of the
      symbiont population. Vertically transmitted symbionts, as well as those hosted
      intracellularly, are more likely to form clonal populations within their host.
      Conversely, symbiont populations that are environmentally acquired and
      extracellular may be more likely to be heterogeneous/mixed within host
      individuals, as observed in some mytilid bivalves. The symbionts of thyasirid
      bivalves are also extracellular, but limited 16S rRNA sequencing data suggest
      that thyasirid individuals contain uniform symbiont populations. In a recent
      study, Thyasira cf. gouldi individuals from Bonne Bay, Newfoundland, Canada were
      found to host one of three 16S rRNA phylotypes of sulfur-oxidizing
      gammaproteobacteria, suggesting environmental acquisition of symbionts and some
      degree of site-specificity. Here, we use Sanger sequencing of both 16S RNA and
      the more variable ribulose-1,5-bisphosphate carboxylase (RuBisCO) PCR products to
      further examine Thyasira cf. gouldi symbiont diversity at the scale of host
      individuals, as well as to elucidate any temporal or spatial patterns in symbiont
      diversity within Bonne Bay, and relationships with host OTU or size. We obtained
      symbiont 16S rRNA and RuBisCO Form II sequences from 54 and 50 host individuals,
      respectively, during nine sampling trips to three locations over four years.
      Analyses uncovered the same three closely related 16S rRNA phylotypes obtained
      previously, as well as three divergent RuBisCO phylotypes; these were found in
      various pair combinations within host individuals, suggesting incidents of
      horizontal gene transfer during symbiont evolution. While we found no temporal
      patterns in phylotype distribution or relationships with host OTU or size, some
      spatial effects were noted, with some phylotypes only found within particular
      sampling sites. The sequencing also revealed symbiont populations within
      individual hosts that appeared to be a mixture of different phylotypes, based on
      multiple base callings at divergent sites. This work provides further evidence
      that Thyasira cf. gouldi acquires its symbionts from the environment, and
      supports the theory that hosts can harbour symbiont populations consisting of
      multiple, closely related bacterial phylotypes.

PMID- 28761787
TI  - A mutualism without honeydew: what benefits for Melissotarsus emeryi ants and
      armored scale insects (Diaspididae)?
AB  - Mutualisms between ants and sap-sucking insects generally involve clear benefits
      for both partners: the ants provide protection in exchange for honeydew. However,
      a single ant genus associates with armoured scale insects (Diaspididae) that do
      not excrete honeydew. We studied three colonies of Melissotarsus emeryi ants from
      two localities in Mozambique. Vast numbers of the diaspidid Morganella conspicua
      occupied galleries dug by the ants under the bark of living trees. Unlike free
      living M. conspicua and other diaspidids, M. conspicua living with ants are known
      to lack shields, likely because they gain protection against enemies and
      desiccation. Nevertheless, we documented the occurrence of rare individuals with
      shields inside ant galleries, indicating that their glands continue to secrete
      wax and proteins as building material. This is likely to constitute a significant
      portion of the ants' diet, in addition to diaspidid exuviae and excretions from
      the Malpighian tubules. Indeed, Melissotarsus workers cannot walk outside the
      galleries due to modified middle legs, forcing them to obtain all nourishment
      within the tree. Melissotarsus founding queens, however, must locate a suitable
      host tree while flying, and acquire diaspidid crawlers. This mutualism involves
      ants that are highly specialised to chew through living wood, and diaspidids that
      can also live freely outside the bark. It is extremely widespread in Africa and
      Madagascar, recorded from 20 tree families, and harmful effects on plant hosts
      require rapid study.

PMID- 28761788
TI  - Two new species of the Brachycephalus pernix group (Anura: Brachycephalidae) from
      the state of Parana, southern Brazil.
AB  - We describe two new species of miniaturized toadlet in the B. pernix group of
      Brachycephalus (Anura: Brachycephalidae) from the Atlantic Forest of the state of
      Parana, southern Brazil. The first new species is distinguished from all
      congeners by the pale red coloration from the head to the pelvic region, with
      sides of the body and thighs dorsally yellowish green. It is known only from the
      type locality in a cloud forest at altitudes ranging between 1,144-1,228 m a.s.l.
      The second species, although more closely related to B. izecksohni, is
      morphologically similar to B. brunneus in its overall brown coloration, but
      distinct from that species in the color of the iris (black with conspicuous
      golden spots, instead of entirely black). It was found on three mountains, at
      altitudes between 1,095-1,320 m a.s.l., and in vegetation types including cloud
      forest, montane forest, and secondary forest. The two new species exhibit neither
      vertebral fusions nor osteoderms, but one has both a distinct neopalatine and
      well-developed odontoids on the maxillae. We discuss the conservation status of
      both species.

PMID- 28761789
TI  - An exceptionally preserved 110 million years old praying mantis provides new
      insights into the predatory behaviour of early mantodeans.
AB  - Mantodeans or praying mantises are flying insects and well known for their
      raptorial behaviour, mainly performed by their first pair of thoracic appendages.
      We describe here a new, exceptionally preserved specimen of the early mantodean
      Santanmantis axelrodi Grimaldi, 2003 from the famous 110 million years old Crato
      Formation, Brazil. The incomplete specimen preserves important morphological
      details, which were not known in this specific form before for this species or
      any other representative of Mantodea. Unlike in modern representatives or other
      fossil forms of Mantodea not only the first pair of thoracic appendages shows
      adaptations for predation. The femora of the second pair of thoracic appendages
      bear numerous strong, erect spines which appear to have a sharp tip, with this
      strongly resembling the spines of the first pair of thoracic appendages. This
      indicates that individuals of S. axelrodi likely used at least two pairs of
      thoracic appendages to catch prey. This demonstrates that the prey-catching
      behaviour was more diverse in early forms of praying mantises than anticipated.

PMID- 28761790
TI  - Potential wound healing activity of Quercus infectoria formulation in diabetic
      rats.
AB  - BACKGROUND: Quercus infectoria G. Olivier (Fagaceae) nutgalls have been widely
      employed in traditional Asian medicine for several treatments, especially wounds
      and skin disorders. However, the effects of this plant on wound healing have not
      yet been clearly elucidated. This present work was focused on utilization of
      Quercus infectoria (Qi) as a topical agent for chronic wound treatment. METHODS:
      Twenty Qi formulations (QiFs) were pharmaceutically formulated and antibacterial
      activity of all formulations was performed. The best formulation based on an
      antibacterial activity was selected for evaluation of wound healing property.
      Total phenolics, total flavonoids, and an anti-oxidant activity of the selected
      formulation were also investigated. Wound healing activity was assessed in
      streptozotocin-induced diabetic rats and control rats. Streptozotocin injection
      (50 mg/kg) was found to induce marked hyperglycaemia, compared with citrate
      injected controls. Two wounds were created on the upper back of each animal. QiF
      was topically applied three days after wounding to one of the duplicate wounds on
      each animal and physiological saline (control) was applied to the other. All
      wounds were cleaned once a day until wound closure. RESULTS: QiF10, which
      exhibited antibacterial and anti-oxidant activities, had the ability to enhance
      the wound healing process in diabetic rats with abundant cellular infiltration,
      collagen deposition, and re-epithelialization when compared with the control.
      DISCUSSION: This study suggested that QiF10 could be a novel alternative
      treatment for diabetic wounds.

PMID- 28761791
TI  - Mortality, recovery, and community shifts of scleractinian corals in Puerto Rico
      one decade after the 2005 regional bleaching event.
AB  - This work analyzes the mortality, recovery, and shifts in the composition of
      scleractinian corals from Puerto Rico one decade after the 2005 regional coral
      bleaching event. Temporal and spatial patterns of coral community structure were
      examined using a stratified, non-random sampling approach based on five permanent
      transects per reef at 16 reef stations. A negative correlation between percent
      coral cover loss and light attenuation coefficient (Kd490) was observed,
      suggesting that light attenuation, as influenced by water turbidity and depth,
      played a major role in coral protection during the bleaching event ("sunblock
      effect"). Responses of coral assemblages varied after the bleaching event,
      including shifts of cover from massive corals (Orbicella spp.) to opportunistic
      (Porites astreoides) and branching corals (Madracis auretenra, P. porites) and/or
      turf algae; partial recovery of reef substrate cover by O. annularis complex; and
      no measurable changes in coral assemblages before and after the event.

PMID- 28761793
TI  - Miocene spider Maevia eureka nov. sp. (Araneae: Salticidae).
AB  - A new fossil species of salticid spider (Araneae: Salticidae) is described based
      on an amber-embedded specimen. The specimen was collected from lignite-sandstone
      early-mid Miocene sediments near the town of Totolapa in Chiapas, southwestern
      Mexico. The diagnosis and description is supported by key characters that best
      match the genus Maevia Koch, 1846. Thus, this new fossil species has been named
      Maevia eureka nov. sp. This fossil shows closer affinities in epygine traits with
      extant specimens grouped around the species Maevia poultoni Peckham & Peckham,
      1901. This represents the first known fossil species within Maevia and the
      southernmost record of the genus in North America that shows Nearctic
      relationships.

PMID- 28761792
TI  - Plantar pressure distribution of ostrich during locomotion on loose sand and
      solid ground.
AB  - BACKGROUND: The ostrich is a cursorial bird with extraordinary speed and
      endurance, especially in the desert, and thus is an ideal large-scale animal
      model for mechanic study of locomotion on granular substrate. METHODS: The
      plantar pressure distributions of ostriches walking/running on loose sand/solid
      ground were recorded using a dynamic pressure plate. RESULTS: The center of
      pressure (COP) on loose sand mostly originated from the middle of the 3rd toe,
      which differed from the J-shaped COP trajectory on solid ground. At mid-stance, a
      high-pressure region was observed in the middle of the 3rd toe on loose sand, but
      three high-pressure regions were found on solid ground. The gait mode
      significantly affected the peak pressures of the 3rd and 4th toes (p = 1.5 * 10-6
      and 2.39 * 10-8, respectively), but not that of the claw (p = 0.041). The effects
      of substrate were similar to those of the gait mode. DISCUSSION: Ground reaction
      force trials of each functional part showed the 3rd toe bore more body loads and
      the 4th toe undertook less loads. The pressure distributions suggest balance
      maintenance on loose sand was provided by the 3rd and 4th toes and the angle
      between their length axes. On loose sand, the middle of the 3rd toe was the first
      to touch the sand with a smaller attack angle to maximize the ground reaction
      force, but on solid ground, the lateral part was the first to touch the ground to
      minimize the transient loading. At push-off, the ostrich used solidification
      properties of granular sand under the compression of the 3rd toe to generate
      sufficient traction.

PMID- 28761794
TI  - Newly incident cannabis use in the United States, 2002-2011: a regional and state
      level benchmark.
AB  - BACKGROUND: Cannabis use and cannabis regulatory policies recently re-surfaced as
      noteworthy global research and social media topics, including claims that
      Mexicans have been sending cannabis and other drug supplies through a porous
      border into the United States. These circumstances prompted us to conduct an
      epidemiological test of whether the states bordering Mexico had exceptionally
      large cannabis incidence rates for 2002-2011. The resulting range of cannabis
      incidence rates disclosed here can serve as 2002-2011 benchmark values against
      which estimates from later years can be compared. METHODS: The population under
      study is 12-to-24-year-old non-institutionalized civilian community residents of
      the US, sampled and assessed with confidential audio computer-assisted self
      interviews (ACASI) during National Surveys on Drug Use and Health, 2002-2011
      (aggregate n ~ 420,000) for which public use datasets were available. We
      estimated state-specific cannabis incidence rates based on independent
      replication sample surveys across these years, and derived meta-analysis
      estimates for 10 pre-specified regions, including the Mexico border region.
      RESULTS: From meta-analysis, the estimated annual incidence rate for cannabis use
      in the Mexico Border Region is 5% (95% CI [4%-7%]), which is not an exceptional
      value relative to the overall US estimate of 6% (95% CI [5%-6%]). Geographically
      quite distant from Mexico and from states of the western US with liberalized
      cannabis policies, the North Atlantic Region population has the numerically
      largest incidence estimate at 7% (95% CI [6%-8%]), while the Gulf of Mexico
      Border Region population has the lowest incidence rate at 5% (95% CI [4%-6%]).
      Within the set of state-specific estimates, Vermont's and Utah's populations have
      the largest and smallest incidence rates, respectively (VT: 9%; 95% CI [8%-10%];
      UT: 3%; 95% CI [3%-4%]). DISCUSSION: Based on this study's estimates, among 12-to
      24-year-old US community residents, an estimated 6% start to use cannabis each
      year (roughly one in 16). Relatively minor variation in region-wise and state
      level estimates is seen, although Vermont and Utah might be exceptional. As of
      2011, proximity to Mexico, to Canada, and to the western states with liberalized
      policies apparently has induced little variation in cannabis incidence rates. Our
      primary intent was to create a set of benchmark estimates for state-specific and
      region-specific population incidence rates for cannabis use, using meta-analysis
      based on independent US survey replications. Public health officials and policy
      analysts now can use these benchmark estimates from 2002-2011 for planning, and
      in comparisons with newer estimates.

PMID- 28761795
TI  - Geometric morphometrics reveals sex-differential shape allometry in a spider.
AB  - Common scientific wisdom assumes that spider sexual dimorphism (SD) mostly
      results from sexual selection operating on males. However, testing predictions
      from this hypothesis, particularly male size hyperallometry, has been restricted
      by methodological constraints. Here, using geometric morphometrics (GMM) we
      studied for the first time sex-differential shape allometry in a spider (Donacosa
      merlini, Araneae: Lycosidae) known to exhibit the reverse pattern (i.e., male
      biased) of spider sexual size dimorphism. GMM reveals previously undetected sex
      differential shape allometry and sex-related shape differences that are size
      independent (i.e., associated to the y-intercept, and not to size scaling).
      Sexual shape dimorphism affects both the relative carapace-to-opisthosoma size
      and the carapace geometry, arguably resulting from sex differences in both
      reproductive roles (female egg load and male competition) and life styles
      (wandering males and burrowing females). Our results demonstrate that body
      portions may vary modularly in response to different selection pressures, giving
      rise to sex differences in shape, which reconciles previously considered mutually
      exclusive interpretations about the origins of spider SD.

PMID- 28761796
TI  - The salivary gland salivation stimulating peptide from Locusta migratoria (Lom-SG
      SASP) is not a typical neuropeptide.
AB  - The salivary gland salivation stimulating peptide was identified from the
      salivary glands of the migratory locust by its ability to stimulate cAMP
      production in the same tissue. The gene coding for this peptide has recently been
      identified and been shown to code for a precursor consisting of a signal peptide,
      several copies of the peptide separated by Lys-Arg doublets and a few other
      peptides. These data are consistent with it being a neuropeptide. However,
      antiserum raised to this peptide labels the acini of the salivary glands while RT
      PCR only gives positive results in the salivary gland, but not in any ganglion of
      the central nervous system. Thus, this peptide is not a typical neuropeptide as
      previously assumed.

PMID- 28761797
TI  - Correlated evolution of sternal keel length and ilium length in birds.
AB  - The interplay between the pectoral module (the pectoral girdle and limbs) and the
      pelvic module (the pelvic girdle and limbs) plays a key role in shaping avian
      evolution, but prior empirical studies on trait covariation between the two
      modules are limited. Here we empirically test whether (size-corrected) sternal
      keel length and ilium length are correlated during avian evolution using
      phylogenetic comparative methods. Our analyses on extant birds and Mesozoic birds
      both recover a significantly positive correlation. The results provide new
      evidence regarding the integration between the pelvic and pectoral modules. The
      correlated evolution of sternal keel length and ilium length may serve as a
      mechanism to cope with the effect on performance caused by a tradeoff in muscle
      mass between the pectoral and pelvic modules, via changing moment arms of muscles
      that function in flight and in terrestrial locomotion.

PMID- 28761799
TI  - Waugh's Syndrome: Report of Two Children with Intussusception.
AB  - Waugh's syndrome (WS) is the rare association of intussusception and intestinal
      malrotation. We present two such cases in a 5-month-old infant and a 9-year-old
      girl. Both patients presented with intussusception and were diagnosed with
      malrotation during workup and surgical exploration. We conclude that the
      possibility of intestinal malrotation must be taken into consideration while
      managing children with intussusception.

PMID- 28761798
TI  - A data set with kinematic and ground reaction forces of human balance.
AB  - This article describes a public data set containing the three-dimensional
      kinematics of the whole human body and the ground reaction forces (with a dual
      force platform setup) of subjects who were standing still for 60 s in different
      conditions, in which the subjects' vision and the standing surface were
      manipulated. Twenty-seven young subjects and 22 old subjects were evaluated. The
      data set comprises a file with metadata plus 1,813 files with the ground reaction
      force (GRF) and kinematics data for the 49 subjects (three files for each of the
      12 trials plus one file for each subject). The file with metadata has information
      about each subject's sociocultural, demographic, and health characteristics. The
      files with the GRF have the data from each force platform and from the resultant
      GRF (including the center of pressure data). The files with the kinematics
      contain the three-dimensional positions of 42 markers that were placed on each
      subject's body and 73 calculated joint angles. In this text, we illustrate how to
      access, analyze, and visualize the data set. All the data is available at
      Figshare (DOI: 10.6084/m9.figshare.4525082), and a companion Jupyter Notebook
      presents programming code to access the data set, generate analyses and other
      examples. The availability of a public data set on the Internet that contains
      these measurements and information about how to access and process this data can
      potentially boost the research on human postural control, increase the
      reproducibility of studies, and be used for training and education, among other
      applications.

PMID- 28761800
TI  - Pancreatic Kaposiform Hemangioendothelioma Not Responding to Sirolimus.
AB  - Background  Kaposiform hemangioendothelioma (KHE) is a vascular tumor frequently
      associated with Kasabach-Merritt phenomenon (KMP), characterized by severe
      thrombocytopenia and consumptive coagulopathy. Visceral involvement in KHE is
      rare. In our recent experience, sirolimus has shown to be an effective treatment
      in cutaneous KHE, becoming indeed the treatment of choice in KMP. We report a
      case of pancreatic KHE associated with KMP and refractory to sirolimus. Case
      Report  A 4-month-old infant is referred for obstructive jaundice (10 mg/dL
      conjugated bilirubin) secondary to vascular pancreatic tumor. Magnetic resonance
      (MR) and immunohistochemistry were compatible with KHE, but the tumor was
      considered unresectable. We initiated sirolimus (0.8 mg/m 2 /12 h) to treat KMP,
      and interventional radiology was performed for percutaneous biliary diversion.
      This procedure prompted KMP (platelets: 51,000/uL). Sirolimus treatment for 7
      days showed no effect; therefore, we started our VAT protocol
      (vincristine/aspirine/ticlopidin) with great response after 10 days (platelets:
      3,70,000/uL). Three months later, percutaneous biliary diversion was replaced by
      a biliary stent. The tumor disappeared leaving fibrosis and dilatation of biliary
      tract needing hepaticojejunostomy 6 months later. Discussion  It is difficult to
      establish protocols for an unusual presentation of a tumor with different
      targets. This is a reason collaborative multicenter studies should be performed.
      Management of obstructive jaundice secondary to a tumor that usually regresses in
      10 years is an added challenge; therefore, the management should be led by a
      multidisciplinary team. Sirolimus treatment in cutaneous KHE has been described
      as successful in the literature, as well as in our own experience; however, it
      failed in our first patient with visceral KHE. We need to investigate the
      different response to pharmacological agents in tumors with similar
      histopathology, but with visceral involvement.

PMID- 28761802
TI  - A case of tinea incognita and differential diagnosis of figurate erythema.
AB  - A patient with tinea incognita is presented together with a review of the
      literature of figurate erythema. Figurate lesions are emblematic for dermatology
      and perhaps the most picturesque efflorescences. The differential diagnosis can
      be broad and sometimes challenging. Many clinical entities with resembling
      primary and secondary efflorescences have to be considered as differentials and
      can be due to anti-infectious, paraneoplastic, allergic, autoimmune or other
      immune reactions.

PMID- 28761801
TI  - Gastrointestinal Bleed from a Left Ventricle to Colonic Interposition Graft
      Fistula following an Esophagectomy.
AB  - Colonic interposition grafts are commonly used as an esophageal conduit following
      esophageal resection. Significant morbidity is associated with this
      reconstruction due to the nature of the operation. Many of the complications
      associated with this procedure have clear management strategies; however, there
      is a paucity of data when it comes to managing rare complications. In this
      report, we discuss the presentation, operative intervention, and postoperative
      care of a patient who presented with a left ventricle to esophageal colonic
      interposition graft fistula.

PMID- 28761804
TI  - Partial ambulatory management of severe secondary spontaneous pneumothorax.
AB  - Secondary spontaneous pneumothorax can be difficult to manage especially in
      patients with advanced lung disease and respiratory failure. Such patients are
      unfit for surgery and may endure prolonged hospital stays with chest drains in
      situ. We describe two such cases where the air leak was persistent despite
      conventional management. Ambulatory devices which we ordinarily use to manage
      pneumothoraces in patients with a good lung reserve, were employed as a
      palliative measure. The strategy not only allowed the patients to return home,
      but also resulted in healing of the air leak which had persisted with
      conventional management.

PMID- 28761803
TI  - Invasive aspergillosis in a patient with end stage renal disease.
AB  - Invasive aspergillosis caused by A. Fumigatus, almost occurs in immunocompromised
      hosts and has a poor prognosis. We report a case of invasive Aspergillosis in a
      15-year-old boy with ESRD. He was initially diagnosed as lobar pneumonia and
      peritonitis. When he complained for lower extremity weakness and had convulsions,
      a solid mass originated from right lung compresses the spinal cord and
      intracranial hemorrhagic abscesses were found on MRI. The biopsy specimen showed
      hypae of aspergillus-spp and he died on 12th day.

PMID- 28761806
TI  - Scleroderma-related interstitial lung disease.
AB  - Scleroderma-related interstitial lung disease (SSc-ILD) is a pulmonary fibrosing
      disorder characterized by systemic inflammation and progressive scarring of the
      lungs that leads to respiratory failure. Although certain immunosuppressive
      therapies may slow disease progression, current treatment strategies are not
      curative; consequently, SSc-ILD continues to be a major cause of morbidity and
      mortality. We present four cases of SSc-ILD that emphasize the importance of
      early screening and detection, close follow-up, and aggressive management. We
      also highlight the need for well-conducted clinical trials designed to identify
      new and effective treatments.

PMID- 28761805
TI  - EGFR or PD-L1 decision for first line therapy in a case series of EGFR positive
      and PD-L1 >50.
AB  - Targeted therapies are on the market for the past five years and recently
      pembrolizumab was approved as first line treatment for patients with PD-L1 >50%.
      We present three cases of patients which had epidermal growth factor receptor
      positive expression and programmed death-ligand 1 (PD-L1), PD-L1 >50%
      overexpression.

PMID- 28761807
TI  - Minocycline induced lupus with yellow colored chylous exudative pleural effusion.
AB  - Ninety years old male was admitted to hospital due to breathlessness. The
      prominent findings were extensive blue-grey skin pigmentation and large left
      chylothorax. Drug induced lupus was diagnosed due to either minocycline chronic
      treatment or no alternative illness to explain his sub-acute disease. Minocycline
      therapy was stopped with gradual improvement of pleural effusion and skin
      discoloration. This case is the first presentation of minocycline induced lupus
      with chylothorax.

PMID- 28761808
TI  - Machine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor
      imaging study.
AB  - Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental
      syndrome that has been studied intensively in order to understand relationships
      between the genetic microdeletion, brain development, cognitive function, and the
      emergence of psychiatric symptoms. White matter microstructural abnormalities
      identified using diffusion tensor imaging methods have been reported to affect a
      variety of neuroanatomical tracts in 22q11.2DS. In the present study, we sought
      to combine two discovery-based approaches: (1) white matter query language was
      used to parcellate the brain's white matter into tracts connecting pairs of 34,
      bilateral cortical regions and (2) the diffusion imaging characteristics of the
      resulting tracts were analyzed using a machine-learning method called support
      vector machine in order to optimize the selection of a set of imaging features
      that maximally discriminated 22q11.2DS and comparison subjects. With this unique
      approach, we both confirmed previously-recognized 22q11.2DS-related abnormalities
      in the inferior longitudinal fasciculus (ILF), and identified, for the first
      time, 22q11.2DS-related anomalies in the middle longitudinal fascicle and the
      extreme capsule, which may have been overlooked in previous, hypothesis-guided
      studies. We further observed that, in participants with 22q11.2DS, ILF metrics
      were significantly associated with positive prodromal symptoms of psychosis.

PMID- 28761809
TI  - Evaluating single-point quantitative magnetization transfer in the cervical
      spinal cord: Application to multiple sclerosis.
AB  - Spinal cord (SC) damage is linked to clinical deficits in patients with multiple
      sclerosis (MS), however, conventional MRI methods are not specific to the
      underlying macromolecular tissue changes that may precede overt lesion detection.
      Single-point quantitative magnetization transfer (qMT) is a method that can
      provide high-resolution indices sensitive to underlying macromolecular
      composition in a clinically feasible scan time by reducing the number of MT
      weighted acquisitions and utilizing a two-pool model constrained by empirically
      determined constants. As the single-point qMT method relies on a priori
      constraints, it has not been employed extensively in patients, where these
      constraints may vary, and thus, the biases inherent in this model have not been
      evaluated in a patient cohort. We, therefore, addressed the potential biases in
      the single point qMT model by acquiring qMT measurements in the cervical SC in
      patient and control cohorts and evaluated the differences between the control and
      patient-derived qMT constraints (kmf, T2fR1f, and T2m) for the single point
      model. We determined that the macromolecular to free pool size ratio (PSR)
      differences between the control and patient-derived constraints are not
      significant (p > 0.149 in all cases). Additionally, the derived PSR for each
      cohort was compared, and we reported that the white matter PSR in healthy
      volunteers is significantly different from lesions (p < 0.005) and normal
      appearing white matter (p < 0.02) in all cases. The single point qMT method is
      thus a valuable method to quantitatively estimate white matter pathology in MS in
      a clinically feasible scan time.

PMID- 28761810
TI  - Cerebellar degeneration affects cortico-cortical connectivity in motor learning
      networks.
AB  - The cerebellum plays an important role in motor learning as part of a cortico
      striato-cerebellar network. Patients with cerebellar degeneration typically show
      impairments in different aspects of motor learning, including implicit motor
      sequence learning. How cerebellar dysfunction affects interactions in this
      cortico-striato-cerebellar network is poorly understood. The present study
      investigated the effect of cerebellar degeneration on activity in causal
      interactions between cortical and subcortical regions involved in motor learning.
      We found that cerebellar patients showed learning-related increase in activity in
      two regions known to be involved in learning and memory, namely parahippocampal
      cortex and cerebellar Crus I. The cerebellar activity increase was observed in
      non-learners of the patient group whereas learners showed an activity decrease.
      Dynamic causal modeling analysis revealed that modulation of M1 to cerebellum and
      putamen to cerebellum connections were significantly more negative for sequence
      compared to random blocks in controls, replicating our previous results, and did
      not differ in patients. In addition, a separate analysis revealed a similar
      effect in connections from SMA and PMC to M1 bilaterally. Again, neural network
      changes were associated with learning performance in patients. Specifically,
      learners showed a negative modulation from right SMA to right M1 that was similar
      to controls, whereas this effect was close to zero in non-learners. These results
      highlight the role of cerebellum in motor learning and demonstrate the functional
      role cerebellum plays as part of the cortico-striato-cerebellar network.

PMID- 28761812
TI  - Spatio-temporal variation in prevalence and intensity of trematodes responsible
      for waterfowl die-offs in faucet snail-infested waterbodies of Minnesota, USA.
AB  - Several non-native trematodes hosted by the invasive Eurasian faucet snail,
      Bithynia tentaculata, have been causing die-offs of waterfowl in the Midwestern
      United States and Canada for several decades. Because of the potential
      implications of these die-offs on waterfowl in non-native settings, it is
      necessary to better understand the trematodes that cause the die-offs. Here, we
      studied the spatio-temporal dynamics of two trematodes, Cyathocotyle bushiensis
      and Sphaeridiotrema spp., known to infect waterfowl in northern Minnesota, USA,
      via their intermediate host, the faucet snail (Bithynia tentaculata). We studied
      prevalence (% of snails infected within a sample) and intensity (mean number of
      parasites per infected snail within a sample) of faucet snail infection with
      these two trematodes in small lakes, large lakes, ponds, and rivers in northern
      Minnesota in the spring, summer, and fall of 2011-2013. We tested whether
      parasite prevalence and infection intensity could be explained spatially (as a
      function of the abundance of faucet snails, average snail size, water depth, and
      proximity to known waterfowl groups) and temporally (across years and seasons)
      using generalized estimating equation models. The spatial and temporal patterns
      we observed varied within and among waterbodies. For both parasite species,
      parasite prevalence and intensity of infection were consistently higher in
      samples with larger snails and in deeper portions of the waterbodies. In Lake
      Winnibigoshish, prevalence was lower farther from the large waterfowl groups we
      observed, but the abundance of snails in a sample had no effect on prevalence or
      intensity of infection. Our findings help improve understanding of this multi
      species system, but also illustrate the complexity of modeling the spatial and
      temporal dynamics of infections in waterbodies that are so variable in size,
      shape, waterfowl use, and function.

PMID- 28761811
TI  - Frontal alpha asymmetry as a diagnostic marker in depression: Fact or fiction? A
      meta-analysis.
AB  - BACKGROUND: Frontal alpha asymmetry (FAA) has frequently been reported as
      potential discriminator between depressed and healthy individuals, although
      contradicting results have been published. The aim of the current study was to
      provide an up to date meta-analysis on the diagnostic value of FAA in major
      depressive disorder (MDD) and to further investigate discrepancies in a large
      cross-sectional dataset. METHODS: SCOPUS database was searched through February
      2017. Studies were included if the article reported on both MDD and controls,
      provided an FAA measure involving EEG electrodes F3/F4, and provided data
      regarding potential covariates. Hedges' d was calculated from FAA means and
      standard deviations (SDs). Potential covariates, such as age and gender, were
      explored. Post hoc analysis was performed to elucidate interindividual
      differences that could explain interstudy discrepancies. RESULTS: 16 studies were
      included (MDD: n = 1883, controls: n = 2161). After resolving significant
      heterogeneity by excluding studies, a non-significant Grand Mean effect size (ES)
      was obtained (d = - 0.007;CI = [- 0.090]-[0.075]). Crosssectional analyses showed
      a significant three-way interaction for Gender * Age * Depression severity in the
      depressed group, which was prospectively replicated in an independent sample.
      CONCLUSIONS: The main result was a non-significant, negligible ES, demonstrating
      limited diagnostic value of FAA in MDD. The high degree of heterogeneity across
      studies indicates covariate influence, as was confirmed by crosssectional
      analyses, suggesting future studies should address this Gender * Age * Depression
      severity interaction. Upcoming studies should focus more on prognostic and
      research domain usages of FAA rather than a pure diagnostic tool.

PMID- 28761813
TI  - RNA-seq data from different developmental stages of Rafflesia cantleyi floral
      buds.
AB  - Rafflesia cantleyi, known as one of the world's largest flowers, is a specialised
      holoparasite due to dramatic morphological modifications. It possesses highly
      reduced vegetative structure and only appears as a flower for sexual
      reproduction. Moreover, it has an unusual life cycle in that its floral bud
      development takes up to nine months. In order to fully understand the highly
      modified floral organ structure and long life cycle of R. cantleyi, we used
      Illumina sequencing technology (HiSeq) for sequence generation followed by de
      novo assembly of sequence reads. We obtained the RNA-seq data from three
      different stages of floral bud, representing the early, mid and advanced
      developmental stages. These data are available via BioProject accession number
      PRJNA378435. More than 10.3 Gb raw sequence data were generated, corresponding to
      102,203,042 raw reads. Following removal of low-quality reads and trimming of
      adapter sequences, a total of 91,638,836 reads were obtained. De novo assembly of
      these sequences using Trinity resulted in 89,690 unique transcripts with an N50
      of 1653 bp. The obtained transcriptomic data will be useful for further study to
      understand the molecular interactions that result in R. cantleyi floral
      development.

PMID- 28761814
TI  - A novel nonsense ATP7A pathogenic variant in a family exhibiting a variable
      occipital horn syndrome phenotype.
AB  - We report on a family with occipital horn syndrome (OHS) diagnosed in the
      proband's late fifties. A novel ATP7A pathogenic variant (c.4222A > T,
      p.(Lys1408*)), representing the first nonsense variant and the second late
      truncation causing OHS rather than classic Menkes disease, was found to segregate
      in the family. The predicted maintenance of transmembrane domains is consistent
      with a residual protein activity, which may explain the mild clinical
      presentation.

PMID- 28761815
TI  - A pilot study on using rapamycin-carrying synthetic vaccine particles (SVP) in
      conjunction with enzyme replacement therapy to induce immune tolerance in Pompe
      disease.
AB  - A major obstacle to enzyme replacement therapy (ERT) with recombinant human acid
      alpha-glucosidase (rhGAA) for Pompe disease is the development of high titers of
      anti-rhGAA antibodies in a subset of patients, which often leads to a loss of
      treatment efficacy. In an effort to induce sustained immune tolerance to rhGAA,
      we supplemented the rhGAA therapy with a weekly intravenous injection of
      synthetic vaccine particles carrying rapamycin (SVP-Rapa) during the first 3
      weeks of a 12-week course of ERT in GAA-KO mice, and compared this with three
      intraperitoneal injections of methotrexate (MTX) per week for the first 3 weeks.
      Empty nanoparticles (NP) were used as negative control for SVP-Rapa. Co
      administration of SVP-Rapa with rhGAA resulted in more durable inhibition of anti
      rhGAA antibody responses, higher efficacy in glycogen clearance in skeletal
      muscles, and greater improvement of motor function than mice treated with empty
      NP or MTX. Body weight loss was observed during the MTX-treatment but not SVP
      Rapa-treatment. Our data suggest that co-administration of SVP-Rapa may be an
      innovative and safe strategy to induce durable immune tolerance to rhGAA during
      the ERT in patients with Pompe disease, leading to improved clinical outcomes.

PMID- 28761816
TI  - A simple and fast method for extraction and quantification of cryptophyte
      phycoerythrin.
AB  - The microalgal pigment phycoerythrin (PE) is of commercial interest as natural
      colorant in food and cosmetics, as well as fluoroprobes for laboratory analysis.
      Several methods for extraction and quantification of PE are available but they
      comprise typically various extraction buffers, repetitive freeze-thaw cycles and
      liquid nitrogen, making extraction procedures more complicated. A simple method
      for extraction of PE from cryptophytes is described using standard laboratory
      materials and equipment. The cryptophyte cells on the filters were disrupted at 
      80  degrees C and added phosphate buffer for extraction at 4  degrees C followed
      by absorbance measurement. The cryptophyte Rhodomonas salina was used as a model
      organism. *Simple method for extraction and quantification of phycoerythrin from
      cryptophytes.*Minimal usage of equipment and chemicals, and low labor
      costs.*Applicable for industrial and biological purposes.

PMID- 28761817
TI  - Purely ultrasonic enzyme extraction from activated sludge in an ultrasonic
      cleaning bath.
AB  - Enzymes are important in biological wastewater treatment systems, since they are
      responsible for breakdown of macro- and micropollutants, thereby making the
      pollutants available for metabolism. Enzyme activity has been investigated in
      particular in activated sludge processes, since the activated sludge technology
      is the most important and widely spread wastewater treatment technology used
      today. Various methods have been used to extract enzymes from activated sludge in
      order to measure their activity, these include stirring with additives like
      detergents and cation exchange resins, ultrasonication (with probes) and
      combinations of the three [1], [2], [3]. In this article we describe a method for
      purely ultrasonic enzyme extraction from activated sludge using low power
      ultrasound generated by an ultrasonic bath and no additives. The method
      essentially consists of: *Sonication of the sludge sample using a glass beaker
      and an ultrasonic bath.*Filtration of the sample in order to obtain the enzyme
      extract.*Measurement of enzyme activity by fluorescence spectrometry using a
      substrate that yields a fluorescent product.

PMID- 28761820
TI  - Immuno-biosensor for Detection of CD20-Positive Cells Using Surface Plasmon
      Resonance.
AB  - Purpose: Surface plasmon resonance (SPR) sensing confers a real-time assessment
      of molecular interactions between biomolecules and their ligands. This approach
      is highly sensitive and reproducible and could be employed to confirm the
      successful binding of drugs to cell surface targets. The specific affinity of
      monoclonal antibodies (MAb) for their target antigens is being utilized for
      development of immuno-sensors and therapeutic agents. CD20 is a surface protein
      of B lymphocytes which has been widely employed for immuno-targeting of B-cell
      related disorders. In the present study, binding ability of an anti-CD20 MAb to
      surface antigens of intact target cells was investigated by SPR technique.
      Methods: Two distinct strategies were used for immobilization of the anti-CD20
      MAb onto gold (Au) chips. MUA (11-mercaptoundecanoic acid) and Staphylococcus
      aureus protein A (SpA) were the two systems used for this purpose. A suspension
      of CD20-positive Raji cells was injected in the analyte phase and the resulting
      interactions were analyzed and compared to those of MOLT-4 cell line as CD20
      negative control. Results: Efficient binding of anti-CD20 MAb to the surface
      antigens of Raji cell line was confirmed by both immobilizing methods, whereas
      this MAb had not a noticeable affinity to the MOLT-4 cells. Conclusion: According
      to the outcomes, the investigated MAb had acceptable affinity and specificity to
      the target antigens on the cell surface and could be utilized for immuno
      detection of CD20-positive intact cells by SPR method.

PMID- 28761818
TI  - Effects of Mesenchymal Stem Cell Derivatives on Hematopoiesis and Hematopoietic
      Stem Cells.
AB  - Hematopoiesis is a balance among quiescence, self-renewal, proliferation, and
      differentiation, which is believed to be firmly adjusted through interactions
      between hematopoietic stem and progenitor cells (HSPCs) with the
      microenvironment. This microenvironment is derived from a common progenitor of
      mesenchymal origin and its signals should be capable of regulating the cellular
      memory of transcriptional situation and lead to an exchange of stem cell genes
      expression. Mesenchymal stem cells (MSCs) have self-renewal and differentiation
      capacity into tissues of mesodermal origin, and these cells can support
      hematopoiesis through release various molecules that play a crucial role in
      migration, homing, self-renewal, proliferation, and differentiation of HSPCs.
      Studies on the effects of MSCs on HSPC differentiation can develop modern
      solutions in the treatment of patients with hematologic disorders for more
      effective Bone Marrow (BM) transplantation in the near future. However,
      considerable challenges remain on realization of how paracrine mechanisms of MSCs
      act on the target tissues, and how to design a therapeutic regimen with various
      paracrine factors in order to achieve optimal results for tissue conservation and
      regeneration. The aim of this review is to characterize and consider the related
      aspects of the ability of MSCs secretome in protection of hematopoiesis.

PMID- 28761819
TI  - Legionella Pneumophila and Dendrimers-Mediated Antisense Therapy.
AB  - Finding novel and effective antibiotics for treatment of Legionella disease is a
      challenging field. Treatment with antibiotics usually cures Legionella infection;
      however, if the resultant disease is not timely recognized and treated properly,
      it leads to poor prognosis and high case fatality rate. Legionella pneumophila
      DrrA protein (Defects in Rab1 recruitment protein A)/also known as SidM affects
      host cell vesicular trafficking through modification of the activity of cellular
      small guanosine triphosphatase )GTPase( Rab (Ras-related in brain) function which
      facilitates intracellular bacterial replication within a supporter vacuole. Also,
      Legionella pneumophila LepA and LepB (Legionella effector protein A and B)
      proteins suppress host-cell Rab1 protein's function resulting in the cell lysis
      and release of bacteria that subsequently infect neighbour cells. Legionella
      readily develops resistant to antibiotics and, therefore, new drugs with
      different modes of action and therapeutic strategic approaches are urgently
      required among antimicrobial drug therapies;gene therapy is a novel approach for
      Legionnaires disease treatment. On the contrary to the conventional treatment
      approaches that target bacterial proteins, new treatment interventions target DNA
      (Deoxyribonucleic acid), RNA (Ribonucleic acid) species, and different protein
      families or macromolecular complexes of these components. The above approaches
      can overcome the problems in therapy of Legionella infections caused by
      antibiotics resistance pathogens. Targeting Legionella genes involved in
      manipulating cellular vesicular trafficking using a dendrimer-mediated antisense
      therapy is a promising approach to inhibit bacterial replication within the
      target cells.

PMID- 28761821
TI  - Pharmacokinetic Parameters and Over-Responsiveness of Iranian Population to
      Propranolol.
AB  - Purpose: Propranolol is the most widely used treatment for cardiovascular
      diseases. Dosage range in our patients is usually less than the amount mentioned
      in references. The aim of the present study was to clarify whether
      pharmacokinetic differences are able to justify the need for the fewer doses in
      our patients or not. Methods: Twenty healthy volunteers (10 male) at heart center
      of Mazandaran University of Medical Sciences were studied. Samples of blood were
      collected before a single oral dose (40 mg) of Propranolol. Blood samples were
      taken up to 9 hours after dose. Total plasma concentration of Propranolol was
      measured by HPLC. Population Pharmacokinetic analysis was performed using
      population pharmacokinetics modeling software P-Pharm. Results: The mean value
      for oral plasma clearance (CL/F) was 126.59 ml/hr. The corresponding values for
      apparent volume of distribution (V/F), t1/2 beta, maximum blood concentration (C
      max), and time to reach the maximum blood concentration (T max) were 334.12 Lit,
      1.98 hr, 40.25 ng/ml, and 1.68 hr, respectively. The observed mean values of V/F
      of propranolol in the present study were comparable with those reported in the
      literature. However, the mean values of CL/F of propranolol in current study was
      significantly higher than those reported in other population (P-value<0.001).
      Conclusion: This study has confirmed that the pharmacokinetic differences are not
      able to justify over-responsiveness of Iranian population to propranolol.
      Pharmacodynamic differences in responding to beta blocker drugs by Renin
      secretion or having a different sensibility to beta receptors might play a role
      in making our population have a different response to propranolol.

PMID- 28761822
TI  - Optimization of Chitosan and Cellulose Acetate Phthalate Controlled Delivery of
      Methylprednisolone for Treatment of Inflammatory Bowel Disease.
AB  - Purpose: Inflammatory bowel disease (IBD) is a chronic, relapsing and often life
      long disorder. The best way to tackle IBD is to develop a site targeted drug
      delivery. Methylprednisolone is a potent anti-inflammatory steroid. The relative
      potency of methylprednisolone to hydrocortisone is at least four is to one. The
      aim of the present research was to develop a colon targeted drug delivery for
      treatment of IBD. Methods: Compression coated drug delivery system was designed
      and optimised. Core tablet contained drug, croscarmellose sodium (CCS
      superdisintegrant), avicel (binder) and dicalcium phosphate (diluent). Design of
      experiment with 32 factorial design was applied for optimization of compression
      coated delivery. Chitosan and cellulose acetate phthalate were chosen as
      independent variables. Swelling index, hardness and % drug release were dependant
      variables. Results: Core tablet (C5 batch) containing 2.15% CCS showed
      disintegration in less than 10sec. FTIR, UV and DSC study had shown absence of
      any significant physical and chemical interaction between drug and polymers. F8
      was found to be optimised formulation. F8 contained 35% chitosan and 17.5%
      cellulose acetate phthalate. It showed drug release of 86.3% +/- 6.1%, hardness
      6.5 +/- 1.5 and lag time 7 hrs. Simulated media drug release was 97.51 +/- 8.6%
      with 7.5 hrs lag time. The results confirmed that the lag time was highly
      affected by the coating of the polymers as well as the concentration of the
      superdisintegrant used in core tablet. Conclusion: In-vitro and in-vivo results
      confirmed a potential colon targeted drug therapy for treatment of IBD.

PMID- 28761824
TI  - The Effect of Dried Glycyrrhiza Glabra L. Extract on Obesity Management with
      Regard to PPAR-gamma2 (Pro12Ala) Gene Polymorphism in Obese Subjects Following an
      Energy Restricted Diet.
AB  - Purpose: Obesity is a multi-factorial health problem which results from the
      interaction of environmental and genetic factors. The aim of the present study
      was to determine the effects of dried licorice extract with a calorie restricted
      diet on anthropometric indices and insulin resistance with nutrigenetic approach.
      Methods: For this pilot, double-blind, placebo-controlled randomized clinical
      trial, 72 eligible subjects were randomly allocated to Licorice or placebo group.
      They received a low-calorie diet either with a 1.5 g/day of Licorice extract or
      placebo for 8 weeks. Results: There were no significant differences in
      anthropometric indices and dietary intake in genotype subgroups at the baseline.
      Findings indicated that supplementation with Licorice extract did not change
      anthropometric indices and biochemical parameters significantly compared to a
      hypocaloric diet alone. However, from the nutrigenetic point of view, significant
      changes in anthropometric indices and QUICKI were observed in the Pro12Pro
      genotypes compared to the Pro12Ala at the end of the study (p<0.05 in all
      variables). Moreover, no interactive effect of the Licorice supplement and
      Pro12Ala genotype was found. Conclusion: In obese subjects, the Pro/Pro
      polymorphism of the PPAR-gamma2 gene seems to induce favourable effects on
      obesity management. Further studies are needed to clarify whether PPAR-gamma2
      gene polymorphisms or other obesity genes can affect responses to obesity
      treatment.

PMID- 28761823
TI  - Terminal Deoxynucleotidyl Transferase (TdT) Inhibiti on of Cord Blood Derived B
      and T Cells Expansion.
AB  - Purpose: Terminal deoxynucleotidyl transferase(TdT) is a DNA polymerase that is
      present in immature pre-B and pre-T cells. TdT inserts N-nucleotides to the V (D)
      J gene segment during rearrangements of genes, therefore, it plays a vital role
      in the development and variation of the immune system in vertebrates. Here we
      evaluated the relationship between cytokines like interleukin-2 (IL-2),
      interleukin-7 (IL-7), and interleukin-15 (IL-15) and TdT expression in cord blood
      mononuclear cells and also effect of inhibition in the expansion of B and T cells
      derived from cord blood. Methodes: The cord blood mononuclear cells were cultured
      with different combination of cytokines for 21days, which they were harvested in
      definite days (7, 14 and 21) and evaluated by flow cytometry. Results: Our data
      indicated that TdT expression increased in cord blood mononuclear cells using
      immune cell key cytokines without being dependent on the type of cytokines. TdT
      inhibition reduced both the expansion of B and T cells derived from cord blood
      and also declined the apoptosis and proliferation. Considered together, TdT
      played an important role in the control of the expansion of B and T cells derived
      from cord blood. Conclusion: considered together, it was observed that TdT
      expression was increased by cytokines and TdT inhibition not only reduced B and
      Tcells derived from cord blood, but it also affected the rate of apoptosis and
      proliferation.

PMID- 28761825
TI  - Gellified Emulsion of Ofloxacin for Transdermal Drug Delivery System.
AB  - Purpose: Ofloxacin is a fluoroquinolone with broad-spectrum antibacterial action,
      used in treatment of systemic and local infections. Ofloxacin is BCS class II
      drug having low solubility, high permeability with short half-life. The present
      work was aimed to design, develop and optimize gellified emulsion of Ofloxacin to
      provide site targeted drug delivery. Transdermal drug delivery will enhance the
      bioavailability of the drug giving controlled drug release. Methods: Transdermal
      drug delivery system was designed with gelling agent (Carbopol 940 and HPMC
      K100M), oil phase (oleic acid) and emulsifying agent (Tween 80: Span 80). Effect
      of concentration of gelling agent on release of drug from transdermal delivery
      was studied by 32 factorial design. Emulgel was evaluated for physical
      appearance, pH, drug content, viscosity, spreadability, antimicrobial activity,
      in- vitro diffusion study and ex-vivo diffusion study. Results: FE-SEM study of
      the emulsion batch B5 has revealed formation of emulsion globules of
      approximately size 6-8 um with -11.2 mV zeta potential showing good stability for
      the emulsion. Carbopol 940 had shown greater linear effect on drug release and
      viscosity of the formulations due to its high degree of gelling. In-vitro
      diffusion study through egg membrane had shown 88.58+/-1.82 % drug release for
      optimized batch F4. Ex-vivo diffusion study through goat skin indicated 76.68 +/-
      2.52% drug release. Conclusion: Controlled release Ofloxacin emulgel exhibiting
      good in-vitro and ex-vivo drug release proving good antimicrobial property was
      formulated.

PMID- 28761826
TI  - The Inhibitory Effect of Ginger Extract on Ovarian Cancer Cell Line; Application
      of Systems Biology.
AB  - Purpose: Ginger is a natural compound with anti-cancer properties. The effects of
      ginger and its mechanism on ovarian cancer and its cell line model, SKOV-3, are
      unclear. In this study, we have evaluated the effect of ginger extract on SKOV-3.
      Methods: SKOV-3 cells were incubated with ginger extract for 24, 48 and 72 hours.
      Cell toxicity assay was performed. Different data mining algorithms were applied
      to highlight the most important features contributing to ginger inhibition on the
      SKOV-3 cell proliferation. Moreover, Real-Time PCR was performed to assay p53,
      p21 and bcl-2 genes expression. For co-expression meta-analysis of p53, mutual
      ranking (MR) index and transformation to Z-values (Z distribution) were applied
      on available transcriptome data in NCBI GEO data repository. Results: The ginger
      extract significantly inhibited cancer growth in ovarian cancer cell line. The
      most important attribute was 60 ug/ml concentration which received weights higher
      than 0.50, 0.75 and 0.95 by 90%, 80% and 50% of feature selection models,
      respectively. The expression level of p53 was increased sharply in response to
      ginger treatment. Systems biology analysis and meta-analysis of deposited
      expression value in NCBI based on rank of correlation and Z-transformation
      approach unraveled the key co-expressed genes and co-expressed network of P53, as
      the key transcription factor induced by ginger extract. High co-expression
      between P53 and the other apoptosis-inducing proteins such as CASP2 and DEDD was
      noticeable, suggesting the molecular mechanism underpinning of ginger action.
      Conclusion: We found that the ginger extract has anticancer properties through
      p53 pathway to induce apoptosis.

PMID- 28761827
TI  - Spectroscopic and Spectrometric Methods Used for the Screening of Certain Herbal
      Food Supplements Suspected of Adulteration.
AB  - Purpose: This study was carried out in order to find a reliable method for the
      fast detection of adulterated herbal food supplements with sexual enhancement
      claims. As some herbal products are advertised as "all natural", their
      "efficiency" is often increased by addition of active pharmaceutical ingredients
      such as PDE-5 inhibitors, which can be a real health threat for the consumer.
      Methodes: Adulterants, potentially present in 50 herbal food supplements with
      sexual improvement claims, were detected using 2 spectroscopic methods - Raman
      and Fourier Transform Infrared - known for reliability, reproductibility, and an
      easy sample preparation. GC-MS technique was used to confirm the potential
      adulterants spectra. Results: About 22% (11 out of 50 samples) of herbal food
      supplements with sexual enhancement claims analyzed by spectroscopic and
      spectrometric methods proved to be "enriched" with active pharmaceutical
      compounds such as: sildenafil and two of its analogues, tadalafil and
      phenolphthalein. The occurence of phenolphthalein could be the reason for the non
      relevant results obtained by FTIR method in some samples. 91% of the adulterated
      herbal food supplements were originating from China. Conclusion: The results of
      this screening highlighted the necessity for an accurate analysis of all alleged
      herbal aphrodisiacs on the Romanian market. This is a first such a screening
      analysis carried out on herbal food supplements with sexual enhancement claims.

PMID- 28761828
TI  - Formulation of Menthol-Loaded Nanostructured Lipid Carriers to Enhance Its
      Antimicrobial Activity for Food Preservation.
AB  - Purpose: Due to the antimicrobial property, menthol have significant potential
      for food preservation and foodstuff shelf life improvement. Nevertheless, menthol
      instability, insolubility, and rapid crystallization in aqueous media make it
      unsuitable for used in food products. This work was aimed to prepare menthol
      loaded nanostructured lipid carriers (NLCs) to enhance its antimicrobial
      activity. Methods: Morphology, particle size and size distribution, encapsulation
      efficiency percent (EE%), and physical stability of the optimized formulation,
      prepared by hot melt homogenization method, were characterized by scanning
      electron microscopy, particle size analyzing, gas chromatography, and X-ray
      diffraction (XRD) methods. Minimum inhibitory concentration and minimum
      bactericidal concentration of menthol-loaded NLCs were evaluated and compared
      with conventional menthol emulsion against various Gram-positive (Staphylococcus
      aureus, Bacillus cereus) and Gram-negative bacteria (Escherichia coli), as well
      as one fungus (Candida albicans). Results: Menthol-loaded NLCs were spherically
      shaped nanosized (115.6 nm) particles with narrow size distribution (PDI = 0.2),
      suitable menthol EE% (98.73%), and appropriate physical stability after 90 days
      of storage period. XRD results indicated that menthol was in the amorphous form
      in the nanoparticles matrix. Antibacterial assay results revealed that the
      menthol-loaded NLCs exhibited significantly higher in vitro antimicrobial
      property than conventional menthol emulsion. The results also indicated that
      menthol-loaded NLCs had better effect on fungi than bacteria, and furthermore,
      antibacterial efficiency on Gram-positive bacteria was higher than Gram-negative
      bacteria. Conclusion: In conclusion, NLCs could be a promising carrier for
      improvement of antimicrobial activity and preservation efficacy of essential oils
      in foodstuffs.

PMID- 28761829
TI  - Effects of Pomegranate (Punica Granatum L.) Seed and Peel Methanolic Extracts on
      Oxidative Stress and Lipid Profile Changes Induced by Methotrexate in Rats.
AB  - Purpose: Methotrexate (MTX) is prescribed in many diseases and can result in
      oxidative stress (OS) followed by injuries in some tissues. Antioxidants
      administration are effective in reducing OS. Pomegranate exhibits high anti
      oxidant capacities. This study investigated whether pomegranate seed and peel
      methanolic extracts (PSE and PPE) could protect against MTX-induced OS and lipid
      profile changes in rats. Methods: Forty-eight rats were randomly divided into 6
      groups: control group (normal salin), PSE group (500 mg/kg, orally), PPE group
      (500 mg/kg, orally), MTX group (10 mg/kg, IM), MTX and PSE group, and MTX and PPE
      group. Blood samples were taken for analysis in the end of the procedure.
      Results: The findings showed a significant reduction in Glutathione peroxidase
      (GPx) and Superoxide dismutase (SOD), and an enhancement in malondialdehyde (MDA)
      values after MTX treatment (p < 0.05). SOD and GPx levels reached the levels of
      the control group in MTX+SPE and MTX+PPE groups. No significant differences were
      observed in catalase (CAT) and total antioxidant capacity (TAC) levels between
      groups. The results showed a significant decrease in total cholesterol (TC), low
      density lipoprotein (LDL), and high density lipoprotein (HDL) in the MTX treated
      group (p < 0.01). The values of TC, HDL, and LDL became elevated to the normal
      control levels in the MTX+PSE and MTX+PPE treated groups. Conclusion: The results
      showed the OS induced by MTX and the protective effects of PSE and PPE against
      MTX-induced serum oxidative stress and lipid profile changes in rats.

PMID- 28761830
TI  - Studying the Effect of Sertraline in Reducing Aggressive Behavior in Patients
      with Major Depression.
AB  - Purpose: Depression causes dysfunction in various spheres of individual and
      social life, which is now considered as the fourth-leading cause of the global
      disease burden. Given that violence and aggression associated with depression in
      the community cause serious damage to the family, the prediction, early detection
      and effective treatment of aggressive and violent behavior are essential. The
      present study compared the severity of aggression before and after treatment with
      sertraline in patients with major depression. Methods: This is an intervention
      type study and the study population consisted of patients with depression and
      aggression. The sampling included 23 eligible patients. Data were obtained by
      SCID-I, SCID-II, STAXI-II, BDI-II and was also analyzed using SPSS 23 software.
      Results: The results showed that depression, anger mood, desire to verbally
      express anger, controlling anger and anger control before treatment was reduced
      but the desire for physical expression of anger increased. Conclusion: Obtained
      results in this research support the effect of Sertraline on reduction of
      severity of depression, reduction of severity of symptoms of aggression and anger
      (state of anger, anger feeling, and the tendency to express anger verbally),
      increased controlling external anger and significantly controlling internal
      anger. Hence, Sertraline can be found effective in the treatment of patients with
      depression and aggressive behaviors. Also Sertraline increases tend to cause
      physical representation of anger, then this issue supports the increase in the
      euthanasia behavior in primary days of treatment with SSRI that requires more
      assessments.

PMID- 28761831
TI  - Preparation and Microstructural Characterization of Griseofulvin Microemulsions
      Using Different Experimental Methods: SAXS and DSC.
AB  - Purpose: The objective of the present study is to formulate and evaluate a new
      microemulsion (ME) for topical delivery of griseofulvin. Methods: The
      solubilities of griseofulvin in different combinations of surfactant to co
      surfactant (S/Co ratio) were determined. Accordingly, based on their phase
      diagrams, eight microemulsions were formulated and then evaluated with respect to
      their particle size, surface tension, viscosity, conductivity, zeta potential and
      stability. Their release behavior, Scanning Electron Microscopy (SEM),
      Differential Scanning Calorimetry (DSC), refractory index (RI), pH and Small
      angle-X-ray scattering (SAXS) were also assessed. Results: The results indicated
      that the mean droplet size of the MEs ranged from 30.9 to 84.3 nm. Their zeta
      potential varied from -4.5 to -20.8. Other determined characteristics were
      viscosity: 254-381 cps, pH: 5.34-6.57, surface tension: 41.16- 42.83 dyne.cm-1,
      conductivity: 0.0442 - 0.111 ms.cm-1. The drug release was in the range of 22.4
      to 43.69 percent. Also, hexagonal, cubic and lamellar liquid crystals were
      observed in SAXS experiments. Conclusion: It can be concluded that any alteration
      in MEs constituents directly affects their microstructure, shape, droplet size
      and their other physicochemical properties.

PMID- 28761832
TI  - Anticonvulsant and Antioxidant Effects of Pitavastatin Against Pentylenetetrazol
      Induced Kindling in Mice.
AB  - Purpose: The pleiotropic effects of statins (antioxidant and anti-inflammation)
      have been reported by previous studies. Therefore, we aimed to determine whether
      pitavastatin has protective effects against pentylenetetrazol (PTZ)-induced
      kindling in mice and also whether pitavastatin improves the brain antioxidant
      capacity and attenuates the oxidative injuries in kindled mice. Methods: Twenty
      four mice were randomly divided into four groups (each group n=6); control, PTZ
      kindling and PTZ-kindled rats treated with pitavastatin (1&4 mg/kg). PTZ kindling
      seizures were induced by repetitive intraperitoneal injections of PTZ (65 mg/kg)
      every 48 hours till day twenty-one. Animals received daily oral pitavastatin for
      twenty-one days. Latency, score and duration of the seizures were recorded. The
      activities of catalase (CAT) ad superoxide dismutase (SOD), and likewise the
      contents of malondialdehyde (MDA) and nitrate were assessed in the brains of all
      rats. Results: There was a progressive reduction in latency of the kindled rats
      in the next injections of PTZ. Pitavastatin reduced this value (latency)
      particularly at higher dose. Seizures duration and score also decreased in
      treatment groups. SOD and CAT activities significantly decreased in PTZ-kindling
      group by 62% and 64%, respectively, but pitavastatin did not significantly change
      the SOD and CAT activities. Brain MDA and nitrate significantly increased in PTZ
      kindling group by 53% and 30%, respectively. Pitavastatin at higher dose
      significantly decreased the MDA and nitrate contents of PTZ-kindling rats by 45%
      and 32%, respectively. Conclusion: Our findings revealed that pitavastatin can
      improve the behavioral expression of the PTZ-kindling rats and attenuate the
      seizure-induced oxidative/nitrosative damage.

PMID- 28761833
TI  - Expression of Functional Anti-p24 scFv 183-H12-5C in HEK293T and Jurkat T Cells.
AB  - Purpose: More than half of the diagnostic and therapeutic recombinant protein
      production depends on mammalian-based expression system. However, the generation
      of recombinant antibodies remains a challenge in mammalian cells due to the
      disulfide bond formation and reducing cytoplasm. Therefore, the production of
      functional recombinant antibodies in target cell line is necessary to be
      evaluated before used in therapeutic application such intrabodies against HIV-1.
      Methods: The work was to test expression of a single-chain variable fragment
      (scFv) antibody against HIV-1 Capsid p24 protein in a human mammalian-based
      expression system using HEK293T and Jurkat T cells as a model. Three expression
      plasmid vectors expressing scFv 183-H12-5C were generated and introduced into
      HEK293T. Expression of the scFv was analyzed, while ELISA and immunoblotting
      analysis verified its binding. The evaluation of the recombinant antibody was
      confirmed by HIV-1 replication and MAGI infectivity assay in Jurkat T cells.
      Results: Three plasmid vectors expressing scFv 183-H12-5C was successfully
      engineered in this study. Recombinant antibodies scFv (~29 kDa) and scFv-Fc (~52
      kDa) in the cytoplasm of HEK293T were effectively obtained by transfected the
      cells with engineered pCDNA3.3-mu-IgGk-scFv 183-H12-5C and pCMX2.5-scFv 183-H12
      5C-hIgG1-Fc plasmid vectors respectively. scFv and scFv-Fc are specifically bound
      recombinant p24, and HIV-1 derived p24 (gag) evaluated by ELISA and Western blot.
      Jurkat T cells transfected by pCDNA3.3-scFv 183-H12-5C inhibit the replication
      competent NL4-3 viral infectivity up to 60%. Conclusion: Anti-p24 scFv 183-H12-5C
      antibody generated is suitable to be acted as intrabodies and may serve as a
      valuable tool for the development of antibody-based biotherapeutics against HIV
      1.

PMID- 28761835
TI  - Evaluation of Vitamin D3 and D2 Stability in Fortified Flat Bread Samples During
      Dough Fermentation, Baking and Storage.
AB  - Purpose: Vitamin D, a fat-soluble secosteroid, has a significant role in bone
      metabolism and helps calcium absorption in the body. Since vitamin D
      concentration is altered in fortified foods and dietary supplements, the actual
      amount of vitamin D may differ from the label value. Methods: In this study, the
      concentrations of vitamin D2 and D3 of fortified bread sample were analytically
      determined. For this purpose, dough or homogenized bread sample was saponified
      using potassium hydroxide solution (30%, w/v) at 80 degrees C, and the saponified
      analytes were extracted into n-heptane followed by liquid-liquid extraction. Then
      n-heptane fraction was evaporated to dryness and the sample was reconstituted in
      methanol. The effect of different parameters was evaluated by one variable at one
      time strategy. Results: The analytes concentrations were evaluated in dough
      fermentation, baking and storage steps. The effect of temperature in dough
      fermentation and baking was evaluated at the range of 5-30 and 200-250 degrees C,
      respectively. Also, the fermentation time was studied in the range of 0-120 min.
      The analytes concentrations were followed for 1 to 5 days after baking. The
      results indicated that dough fermentation temperature has no significant effect
      on the concentration of the analytes. On the other hand, when the dough
      fermentation time and baking temperature are increased, the analytes
      concentrations are decreased. Also, the storage duration of the spiked bread
      samples decreased the analytes concentrations after one day. Conclusion: Based on
      the obtained results, baking the dough at high temperatures lead to decrease in
      vitamin levels.

PMID- 28761834
TI  - Development and Optimization of a New Chemoenzymatic Approach for the Synthesis
      of Peracetylated Lactosamine (Intermediate for the Synthesis of Pharmacologically
      Active Compounds) Monitored by RP- HPLC Method.
AB  - Purpose: To describe a chemoenzymatic approach joining an enzymatic
      regioselective hydrolysis of peracetylated N-acetyl-alpha-D-glucosamine (A) with
      a mild controlled acyl relocation which resulted 2-acetamido-2 deoxy-1,3,6-tri-O
      acetyl-alpha-D-glucopyranose (1B). Methods: Immobilization of lipase on decaoctyl
      (DSEOD) and octyl-agarose (OSCL) was carried out as reported by the work of
      Bastida et al. The newly developed RP-HPLC method for examining the enzymatic
      hydrolysis was carried out isocratically utilizing a HPLC system. Results: The
      new approach resulted the target compound (B) in 95% yield after purification
      utilizing flash column chromatography. Candida rugosa-lipase immobilized
      ondecaoctyl-sepabeads was the best catalyst in terms of activity and region
      selectivity in the hydrolysis of substrate (A), delivering the deacetylation at
      C6 position (98% general yield). Also, a reversed-phase high-performance liquid
      chromatographic (RP-HPLC) method for controlling the region-selective hydrolysis
      of peracetylated N-acetyl-alpha-D-glucosamine (A) with a mild monitored acyl
      movement which led to 2-acetamido-2-deoxy-1,3,6-tri-O-acetyl-alpha-D
      glucopyranose (1B) has additionally been developed. The developed RP-HPLC method
      was utilized as fingerprints to follow the hydrolysis of substrate (A) and to
      determine its purity and additionally yield. Furthermore, the acquired compound
      (B) was further purified by flash chromatography. Compound (B) was further
      characterized utilizing 1HNMR and mass spectrometry. Conclusion: An efficient
      chemoenzymatic procedure to optimize the preparation of peracetylated lactosamine
      B containing acetyl ester as extraordinary protecting group is presented.
      Compound B is a significant intermediate for the synthesis of pharmacologically
      active compound (e.g. complex oligosaccharides for biochemical, biophysical, or
      biological examinations). Besides, reaction monitoring utilizing HPLC proposes
      more exact information than spectroscopic methods.

PMID- 28761836
TI  - Study of Thermal Analysis Behavior of Fenbendazole and Rafoxanide.
AB  - Purpose: Thermal analysis techniques have been applied to study the thermal
      behavior of fenbendazole (Fen) and rafoxanide (Raf). Semi-empirical molecular
      orbital calculations were used to confirm these results. Methods:
      Thermogravimetric analysis, derivative thermogravimetry, differential thermal
      analysis and differential scanning calorimetry were used to determine the thermal
      behavior and purity of the drugs under investigation. Results: Thermal behavior
      of Fen and Raf were augmented using semi-empirical molecular orbital
      calculations. The purity values were found to be 99.17% and 99.60% for Fen and
      Raf, respectively. Conclusion: Thermal analysis techniques gave satisfactory
      results to obtain quality control parameters such as melting point and degree of
      purity at low cost, furthermore, its simplicity and sensitivity justifies its
      application in quality control laboratories.

PMID- 28761837
TI  - Human Bone Marrow-Derived Mesenchymal Cell Reactions to 316L Stainless Steel: An
      in Vitro Study on Cell Viability and Interleukin-6 Expression.
AB  - Purpose: Human bone marrow-derived mesenchymal cell (hBMC) reactions to 316L
      stainless steel (316L-SS) have never been evaluated. The objective of this study
      was to assess cell viability and interleukin-6 expression of hBMC cultures upon
      treatment with a 316L-SS implant. Methods: A cytotoxicity analysis was conducted
      with a 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium (MTT) assay after a
      period of 24, 48 and 72 hours of incubation. Expression of interleukin-6 was
      measured using enzyme-linked immunosorbent assay (ELISA). Results: Cell viability
      measurement was performed via IC50 formula. All treatment group showed a > 50 %
      cell viability with a range of 56,5 - 96,9 % at 24 hours, 51,8-77,3% at 48 hours
      and 70,1- 120 % at 72 hours. Interleukin-6 expression was downregulated
      subsequent to treatment with 316L-SS compared to the control group. Conclusion:
      We found that 316L-SS did not exhibit toxicity towards hBMC culture.

PMID- 28761839
TI  - A Real-World Study to Assess the Effectiveness of Itolizumab in Patients with
      Chronic Plaque Psoriasis.
AB  - BACKGROUND: While clinical trial data on the efficacy of itolizumab in the
      management of psoriasis is relatively well documented, data on the effectiveness
      of this humanized IgG1 monoclonal antibody in real-world settings is sparse.
      AIMS: The current study assessed the effectiveness of itolizumab in real-world
      settings. MATERIALS AND METHODS: This study assessed psoriasis area severity
      index (PASI), dermatology quality of life index (DLQI), safety, and tolerability
      data from a registry of itolizumab maintained by Syngene International,
      Bangalore. Registry data of 155 patients who were prescribed itolizumab at a dose
      of 1.6 mg/kg every 2 weeks for the first 12 weeks followed by 1.6 mg/kg every 4
      weeks for up to 24 weeks for chronic plaque psoriasis. RESULTS: In the study,
      35.48% completed itolizumab for 12 weeks and 76.59% of these patients achieved
      PASI 75. Furthermore, 24.51% patients completed the full Itolizumab regimen for
      24 weeks, of whom 92.01% patients achieved PASI 75. The mean percent change in
      DLQI scores at weeks 12 and 24 were 60.19 and 82.72, respectively. Adverse events
      and infusion reactions noted in the study were generally of mild to moderate
      severity. CONCLUSION: Itolizumab is a safe and effective option in treatment
      compliant patients with chronic plaque psoriasis. Effects of putative compliance
      modulators such as cost, route of administration, and delayed onset of action
      warrant further investigation.

PMID- 28761840
TI  - Comparative Analysis of Serum Copper, Iron, Ceruloplasmin, and Transferrin Levels
      in Mild and Severe Psoriasis Vulgaris in Iranian Patients.
AB  - BACKGROUND: There is a great body of evidence indicating that some inflammatory
      skin diseases, such as psoriasis, are mediated by oxidative stress. Trace metals
      have been shown to be involved in oxidative stress response. Altered trace metal
      homeostasis in psoriasis has been studied. However, limited number of studies has
      focused on the involvement of metal binding proteins in psoriasis. MATERIALS AND
      METHODS: In a case control-study, serum levels of Iron (Fe), Copper (Cu),
      Transferrin (Trf), and Ceruloplasmin (Cp) were measured in 40 psoriasis patients
      and matched healthy controls. The severity of the disease was measured using
      psoriasis area and severity index (PASI), and the association of severity based
      on PASI score and measured elements and proteins was investigated. RESULTS: Forty
      patients with psoriasis (mild: 14 and moderate to severe: 26) and 40 healthy
      controls were included in this study. The serum Fe, Trf, and Cu/Cp levels of the
      patients with psoriasis were statistically lower compared with those of the
      controls; serum levels of Cp was elevated in patients with psoriasis compared to
      controls (P = 0.02). No significant difference was observed between the two
      groups regarding serum levels of Cu (P = 0.07). CONCLUSION: Cu/Cp ratio of the
      patients with psoriasis was statistically lower compared with those of the
      controls.

PMID- 28761838
TI  - Topical Therapies in Psoriasis.
AB  - Topical therapy as monotherapy is useful in psoriasis patients with mild disease.
      Topical agents are also used as adjuvant for moderate-to-severe disease who are
      being concurrently treated with either ultraviolet light or systemic medications.
      Emollients are useful adjuncts to the treatment of psoriasis. Use of older
      topical agents such as anthralin and coal tar has declined over the years.
      However, they are cheaper and can still be used for the treatment of difficult
      psoriasis refractory to conventional treatment. Salicylic acid can be used in
      combination with other topical therapies such as topical corticosteroids (TCS)
      and calcineurin inhibitors for the treatment of thick limited plaques to increase
      the absorption of the latter into the psoriatic plaques. Low- to mid-potent TCS
      are used in facial/flexural psoriasis and high potent over palmoplantar/thick
      psoriasis lesions. The addition of noncorticosteroid treatment can also
      facilitate the avoidance of long-term daily TCS. Tacrolimus and pimecrolimus can
      be used for the treatment of facial and intertriginous psoriasis. Tazarotene is
      indicated for stable plaque psoriasis usually in combination with other therapies
      such as TCS. Vitamin D analogs alone in combination with TCS are useful in stable
      plaques over limbs and palmoplantar psoriasis. Topical therapies for scalp
      psoriasis include TCS, Vitamin D analogs, salicylic acid, coal tar, and anthralin
      in various formulations such as solutions, foams, and shampoos. TCS, vitamin D
      analogs, and tazarotene can be used in the treatment of nail psoriasis.

PMID- 28761841
TI  - Multiple Verrucous Hemangiomas: A Case Report with New Therapeutic Insight.
AB  - Verrucous hemangioma is an uncommon congenital vascular malformation, which may
      clinically masquerade angiokeratoma, lymphangioma circumscriptum, or malignant
      melanoma. Differentiation is essential owing to varied therapeutic and prognostic
      implications. We present a rare case of multiple verrucous hemangiomas in a
      teenage girl who presented with multiple warty lesions over the dorsal aspect of
      the left foot since birth. Magnetic resonance imaging (MRI) scan was suggestive
      of a vascular malformation, and skin biopsy showed ectatic blood vessels
      extending from the papillary dermis into the subcutaneous tissue, diagnostic of
      verrucous hemangioma. A combination of 0.05% halobetasol propionate with 3%
      salicylic acid ointment was advised. This therapeutic intervention resulted in
      significant resolution of the warty lesions over a period of 2 months, following
      which surgical excision was performed. The implication is that we can use a
      combination of super potent topical steroid with salicylic acid as an adjunct to
      surgical resection.

PMID- 28761842
TI  - Cutaneous Squamous Cell Carcinoma in Lupus Vulgaris Caused by Drug Resistant
      Mycobacterium Tuberculosis.
AB  - Tuberculosis (TB) is still a major public health problem in the world, with many
      factors contributing to this burden, including poor living conditions,
      overcrowding, poverty, malnutrition, illiteracy, and rapid spread of human
      immunodeficiency virus infection. Cutaneous tuberculosis is a less common form of
      extrapulmonary tuberculosis, and in this paucibacillary form the diagnosis
      depends on histopathology, tuberculin positivity, and response to treatment. The
      diagnosis is even more difficult in cases with drug resistant Mycobacterium
      tuberculosis due to lack of awareness and lack of facilities to diagnose drug
      resistant tuberculosis. In this article, we describe an unusual case of multidrug
      resistant lupus vulgaris (LV), in a 34-year-old male who responded to anti
      tubercular treatment (ATT) initially, but developed recurrent disease which
      failed to respond to standard four-drug ATT; subsequently, tissue culture showed
      growth of multidrug resistant M. tuberculosis. Subsequently, he also developed
      cutaneous squamous cell carcinoma. This article aims to exemplify a grave
      complication that can occur in long-standing case of LV, the limitations faced by
      clinicians in developing countries where tuberculosis is endemic, and classical
      methods of proving drug resistance are generally unavailable or fail.

PMID- 28761843
TI  - Well-Differentiated Squamous Cell Carcinoma Presenting as Branched Eyelid
      Cutaneous Horn: A Case Report with Review of Literature.
AB  - Cutaneous horns are uncommon lesions consisting of keratotic material, resembling
      that of an animal horn. They account for 4% of all eyelid tumors. We report a
      case of giant cutaneous horn (2 * 1.75 cm) of 4-year duration arising from the
      right lower lid. Growth excision with direct closure of the defect was done.
      Histopathological examination revealed it to be well-differentiated squamous cell
      carcinoma. Most important concern while evaluating cutaneous horns is the
      underlying condition, which may be benign or malignant. Therefore,
      histopathological examination is mandatory.

PMID- 28761844
TI  - Bilateral Lichen Striatus: A Case Report with Review of Literature.
AB  - Lichen striatus is a self-limiting dermatosis presenting with sudden eruption of
      lichenoid papules along the lines of Blaschko. A 5-year-old girl presented with
      asymptomatic hypopigmented linear lesions over both upper limbs. The
      histopathological examination revealed spongiosis, vacuolar alteration of the
      basal layer and lymphocytic exocytosis with a mild-to-moderate perivascular
      mononuclear infiltrate in the dermis. Lichen striatus was diagnosed based upon
      the characteristic clinical and histopathological findings. The pathogenetic
      mechanism of bilateral lichen striatus is unknown at present, however, a somatic
      mutation in two different clones of cells can be a possibility.

PMID- 28761846
TI  - Phaeohyphomycosis of the Face Masquerading as Basal Cell Carcinoma in an
      Immunocompetent Patient.
AB  - Pheohyphomycosis is a rare heterogeneous group of mycotic infections caused by
      dermatiaceous (phaeoid) fungi affecting the skin, subcutaneous tissue, and the
      central nervous system.Involvement of the face is extremely rare, and very few
      cases have been reported in India so far. We reporta case of phaeohyphomycosisin
      a 45-year-old female with 1-year history of a well- defined hypertrophic plaque
      over the right cheek advancing towards the forehead. The lesion was ulcerated
      with rolled-up margins; a provisional clinical diagnosis of basal cell carcinoma
      was given. Histopathology of the skin biopsy revealed numerous multinucleated
      giant cells and fungal hyphae with in and in between the giant cells. Various
      histochemical stains were used toconfirm the presence of fungal hyphae. Melanin
      pigment in the fungus was demonstrated with Masson's Fontana stain. Based on the
      histopathological and histochemical findings, a diagnosis of phaeohyphomycosis
      was given and it was concluded that the disease was more of a histopathological
      than clinical diagnosis. This case is being reported due to its unusual
      presentation and it also highlights the importance of histopathology in the
      diagnosis of this rare disease.

PMID- 28761845
TI  - Angiolymphoid Hyperplasia with Eosinophilia and its Response to the Combination
      of Radiofrequency Ablation and Topical Timolol.
AB  - Angiolymphoid hyperplasia with eosinophilia is a rare vascular disease
      characterized by multiple erythematous to violaceous papules, commonly present on
      the head and neck region. We report a case of a 23-year-old female who presented
      with multiple, erythematous asymptomatic papules on the preauricular region and
      pinna, which on biopsy was suggestive of angiolymphoid hyperplasia. The lesions
      were treated with a novel combination of radiofrequency ablation and topical
      timolol. The lesions healed without scarring and there was no recurrence on 1
      year follow up.

PMID- 28761847
TI  - Bullous Diabeticorum: A Rare Blistering Manifestation of Diabetes.

PMID- 28761848
TI  - Fixed Drug Eruption Induced by Levocetirizine.

PMID- 28761849
TI  - A Rare Case of Coinfection with White Piedra and Pediculosis Capitis.

PMID- 28761850
TI  - Masson's Tumor Presenting as an Asymptomatic Nodule on Lower Lip in a 30-Year-Old
      Male.

PMID- 28761851
TI  - Immunohistochemical Expression of Wt-1 Helps to Differentiate Cutaneous Vascular
      Tumors from Vascular Malformations.

PMID- 28761852
TI  - A Case of Eruptive Syringoma Mimicking Plane Warts.

PMID- 28761853
TI  - Pachyonychia Congenita: Brief Appraisal of History and Current Classification.

PMID- 28761854
TI  - Squamous Cell Carcinoma Arising from Hypertrophic Lichen Planus.

PMID- 28761855
TI  - Perforating Folliculitis Secondary to Bendamustine-Rituximab Chemotherapy: A Case
      Report.

PMID- 28761856
TI  - Psoriasis: An Unusual Autoimmune Manifestation in a Boy with Common Variable
      Immunodeficiency.

PMID- 28761857
TI  - The Whiplash Rash.

PMID- 28761858
TI  - Reply to: Detailed Limitations of Study Help Readers to Interpret Results
      Effectively.

PMID- 28761859
TI  - SkIndia Quiz 39: Pebbly Flexural Skin in a Young Female.

PMID- 28761860
TI  - SkIndia Quiz 40: Papulosquamous Papules and Plaques Covered with Hemorrhagic
      Crusts on the Anterior Trunk.

PMID- 28761861
TI  - Primary Cutaneous Nodular Amyloidosis: A Rare Disease.

PMID- 28761862
TI  - Dermoscopy of Porokeratosis of Mibelli.

PMID- 28761864
TI  - The Need for Subdividing the Enhanced Recovery Program and Evaluation Criteria
      After Colorectal Surgery.

PMID- 28761865
TI  - Limitation and Value of Using the Adenoma Detection Rate for Colonoscopy Quality
      Assurance.

PMID- 28761863
TI  - Management of urinary tract infections in patients with neurogenic bladder:
      challenges and solutions.
AB  - INTRODUCTION: Urinary tract infections (UTIs) are one of the most common
      morbidities in persons with neurogenic lower urinary tract dysfunction (NLUTD).
      They are associated with a significant morbidity and mortality, and they affect
      the quality of life of the affected patients. Diagnosis and treatment of UTI in
      this group of patients are challenging. In this review, the current strategies
      regarding diagnosis, treatment, and prevention are summarized. DIAGNOSTICS: it is
      important to correctly diagnose a UTI, as treatment of bacteriuria should
      strictly be avoided. A UTI is defined as a combination of laboratory findings
      (leukocyturia and bacteriuria) and symptoms. Laboratory findings without symptoms
      are classified as asymptomatic bacteriuria. Routine urine screening is not
      advised. TREATMENT: Only UTI should be treated; treatment of asymptomatic
      bacteriuria is not indicated. Prior to treatment, urine for a urine culture
      should be obtained. Antibiotic treatment for ~7 days is advised. PREVENTION: In
      recurrent UTI, bladder management should be optimized and morphologic causes for
      UTI should be excluded. If UTIs persist, medical prophylaxis should be
      considered. Currently, no prophylactic measure with evidence-based efficacy
      exists. Long-term antibiotic prophylaxis should be used merely as an ultimate
      measure. Among the various mentioned innovative approaches for UTI prevention,
      bacteriophages, intravesical instillations, complementary and alternative
      medicine techniques, and probiotics seem to be most promising. CONCLUSION:
      Recently, several promising innovative options for UTI prophylaxis have been
      developed which may help overcome the current therapeutic dilemma. However,
      further well designed studies are necessary to evaluate the safety and efficacy
      of these approaches.

PMID- 28761866
TI  - Unexpected Appendiceal Pathologies and Preoperative Imaging Studies on Patients
      With Acute Appendicitis.

PMID- 28761867
TI  - Mechanical Bowel Preparation, Do It or Not: When Crossing a River, What Do People
      Do?

PMID- 28761868
TI  - Standardizing the Protocols for Enhanced Recovery From Colorectal Cancer Surgery:
      Are We a Step Closer to Ideal Recovery?
AB  - PURPOSE: Enhanced recovery protocols are being implemented into the standard of
      care in surgical practice. This study aimed to insert a steadfast set of elements
      into the perioperative care pathway to establish an improved recovery program for
      colorectal cancer patients. METHODS: Seventy patients planned for elective
      laparoscopic colorectal resection were randomized into 2 groups: conventional
      recovery group (n = 35) and enhanced recovery group (n = 35). The primary outcome
      was the length of hospital stay. Secondary outcomes included the times of removal
      of nasogastric tubes (NGTs), successful enteral feeding, and removal of drains,
      postoperative complications, intra-hospital mortality, and rate of readmission.
      RESULTS: The mean postoperative hospital stay was 4.49 +/- 0.85 days vs. 13.31 +/
      6.9 days (P < 0.001), the mean time of removal of NGTs was 0.77 +/- 1.031 days
      vs. 3.26 +/- 2.737 days (P < 0.001), the mean time of successful enteral feeding
      was 1.89 +/- 1.13 days vs. 5.46 +/- 1.67 days (P < 0.001), and the mean time for
      removal of intra-abdominal drains was 2.94 +/- 1.056 days vs. 9.06 +/- 3.757 days
      (P < 0.001) for the enhanced and the conventional groups, respectively.
      Complications were significantly lower among patients in the enhanced group
      (25.7% vs. 65.7%) (P = 0.001). The rates of readmission were similar in the 2
      groups. CONCLUSION: Applying definite evidence-based elements to the colorectal
      rehabilitation program significantly boosts the recovery pathway with favorable
      outcomes, including faster recovery of gastrointestinal tract functions, lower
      morbidities, and eventually earlier discharge from the hospital.

PMID- 28761869
TI  - Correlation Between Bowel Preparation and the Adenoma Detection Rate in Screening
      Colonoscopy.
AB  - PURPOSE: The adenoma detection rate is commonly used as a measure of the quality
      of colonoscopy. This study assessed both the association between the adenoma
      detection rate and the quality of bowel preparation and the risk factors
      associated with the adenoma detection rate in screening colonoscopy. METHODS:
      This retrospective analysis involved 1,079 individuals who underwent screening
      colonoscopy at the National Cancer Center between December 2012 and April 2014.
      Bowel preparation was classified by using the Aronchick scale. Individuals with
      inadequate bowel preparations (n = 47, 4.4%) were excluded because additional
      bowel preparation was needed. The results of 1,032 colonoscopies were included in
      the analysis. RESULTS: The subjects' mean age was 53.1 years, and 657 subjects
      (63.7%) were men. The mean cecal intubation time was 6.7 minutes, and the mean
      withdrawal time was 8.7 minutes. The adenoma and polyp detection rates were 28.1%
      and 41.8%, respectively. The polyp, adenoma, and advanced adenoma detection rates
      did not correlate with the quality of bowel preparation. The multivariate
      analysis showed age >= 60 years (hazard ratio [HR], 1.42; 95% confidence interval
      [CI], 1.02-1.97; P = 0.040), body mass index >= 25 kg/m2 (HR, 1.56; 95% CI, 1.17
      2.08; P = 0.002) and current smoking (HR, 1.44; 95% CI, 1.01-2.06; P = 0.014) to
      be independent risk factors for adenoma detection. CONCLUSION: The adenoma
      detection rate was unrelated to the quality of bowel preparation for screening
      colonoscopy. Older age, obesity, and smoking were independent risk factors for
      adenoma detection.

PMID- 28761870
TI  - Unexpected Appendiceal Pathologies and Their Changes With the Expanding Use of
      Preoperative Imaging Studies.
AB  - PURPOSE: The preoperative diagnosis of acute appendicitis is often challenging.
      Sometimes, pathologic results of the appendix embarrass or confuse surgeons.
      Therefore, more and more imaging studies are being performed to increase the
      accuracy of appendicitis diagnoses preoperatively. However, data on the effect of
      this increase in preoperative imaging studies on diagnostic accuracy are limited.
      We performed this study to explore unexpected appendiceal pathologies and to
      delineate the role of preoperative imaging studies in the diagnosis of acute
      appendicitis. METHODS: The medical records of 4,673 patients who underwent an
      appendectomy for assumed appendicitis between 1997 and 2012 were reviewed
      retrospectively. Pathological results and preoperative imaging studies were
      surveyed, and the frequencies of pathological results and preoperative imaging
      studies were investigated. RESULTS: The overall rate of pathology compatible with
      acute appendicitis was 84.4%. Unexpected pathological findings, such as normal
      histology, specific inflammations other than acute appendicitis, neoplastic
      lesions, and other pathologies, comprised 9.6%, 3.3%, 1.2%, and 1.5%,
      respectively. The rate of unexpected pathological results was significantly
      reduced because of the increase in preoperative imaging studies. The decrease in
      normal appendices contributed the most to the reduction while other unexpected
      pathologies did not change significantly despite the increased use of imaging
      studies. This decrease in normal appendices was significant in both male and
      female patients under the age of 60 years, but the differences in females were
      more prominent. CONCLUSION: Unexpected appendiceal pathologies comprised 15.6% of
      the cases. Preoperative imaging studies reduced them by decreasing the negative
      appendectomy rate of patients with normal appendices.

PMID- 28761871
TI  - The Usefulness of Intraoperative Colonic Irrigation and Primary Anastomosis in
      Patients Requiring a Left Colon Resection.
AB  - PURPOSE: The aim of this study is to assess the short-term outcome of
      intraoperative colonic irrigation and primary anastomosis and to suggest the
      usefulness of the procedure when a preoperative mechanical bowel preparation is
      inappropriate. METHODS: This retrospective study included 38 consecutive patients
      (19 male patients) who underwent intraoperative colonic irrigation and primary
      anastomosis for left colon disease between January 2010 and December 2016. The
      medical records of the patients were reviewed to evaluate the patients'
      characteristics, operative data, and postoperative short-term outcomes. RESULTS:
      Twenty-nine patients had colorectal cancer, 7 patients had perforated
      diverticulitis, and the remaining 2 patients included 1 with sigmoid volvulus and
      1 with a perforated colon due to focal colonic ischemia. A diverting loop
      ileostomy was created in 4 patients who underwent a low anterior resection.
      Complications occurred in 15 patients (39.5%), and the majority was superficial
      surgical site infections (18.4%). Anastomotic leakage occurred in one patient
      (2.6%) who underwent an anterior resection due sigmoid colon cancer with
      obstruction. No significant difference in overall postoperative complications and
      superficial surgical site infections between patients with obstruction and those
      with peritonitis were noted. No mortality occurred during the first 30
      postoperative days. The median hospital stay after surgery was 15 days (range, 8
      39 days). CONCLUSION: Intraoperative colonic irrigation and primary anastomosis
      seem safe and feasible in selected patients. This procedure may reduce the burden
      of colostomy in patients requiring a left colon resection with an inappropriate
      preoperative mechanical bowel preparation.

PMID- 28761872
TI  - Urinary Bladder Injury During Colonoscopy Without Colon Perforation.
AB  - We report a case of urinary bladder perforation during colonoscopy. A 67-year-old
      female, who had undergone a transabdominal hysterectomy for uterine myomas 15
      years ago, visited the emergency department with complaint of abdominal pain
      after a screening colonoscopy. Laparoscopic examination revealed severe adhesion
      between the sigmoid colon and the urinary bladder. The urinary bladder wall was
      weakened, and several perforation sites were found. The surgery was converted to
      a laparotomy. After a thorough examination, we performed primary repair for the
      perforation sites, followed by an omentopexy.

PMID- 28761873
TI  - Pneumoretroperitoneum and Sepsis After Transanal Endoscopic Resection of a Rectal
      Lateral Spreading Tumor.
AB  - Transanal endoscopic microsurgery is considered a safe, appropriate, and
      minimally invasive approach, and complications after endoscopic microsurgery are
      rare. We report a case of sepsis and pneumoretroperitoneum after resection of a
      rectal lateral spreading tumor. The patient presented with rectal mucous
      discharge. Colonoscopy revealed a rectal lateral spreading tumor. The patient
      underwent an endoscopic transanal resection of the lesion. He presented with
      sepsis of the abdominal focus, and imaging tests revealed pneumoretroperitoneum.
      A new surgical intervention was performed with a loop colostomy. Despite the
      existence of other reports on pneumoretroperitoneum after transanal endoscopic
      microsurgery, what draws attention to this case is the association with sepsis.

PMID- 28761874
TI  - Underwater Shockwave Pretreatment Process to Improve the Scent of Extracted
      Citrus junos Tanaka (Yuzu) Juice.
AB  - Citrus junos Tanaka (yuzu) has a strong characteristic aroma and thus its juice
      is used in various Japanese foods. Herein, we evaluate the volatile compounds in
      yuzu juice to investigate whether underwater shockwave pretreatment affects its
      scent. A shockwave pretreatment at increased discharge and energy of 3.5 kV and
      4.9 kJ, respectively, increased the content of aroma-active compounds. Moreover,
      the underwater shockwave pretreatment afforded an approximate tenfold increase in
      the scent intensity of yuzu juice cultivated in Rikuzentakata. The proposed
      treatment method exhibited reliable and good performance for the extraction of
      volatile and aroma-active compounds from the yuzu fruit. The broad applicability
      and high reliability of this technique for improving the scent of yuzu fruit
      juice were demonstrated, confirming its potential for application to a wide range
      of food extraction processes.

PMID- 28761875
TI  - Inhibition of Fibrinolysis by Coagulation Factor XIII.
AB  - The inhibitory effect of coagulation factor XIII (FXIII) on fibrinolysis has been
      studied for at least 50 years. Our insight into the underlying mechanisms has
      improved considerably, aided in particular by the discovery that activated FXIII
      cross-links alpha2-antiplasmin (alpha2AP) to fibrin. In this review, the most
      important effects of different cross-linking reactions on fibrinolysis are
      summarized. A distinction is made between fibrin-fibrin cross-links studied in
      purified systems and fibrin-alpha2AP cross-links studied in plasma or whole blood
      systems. While the formation of gamma chain dimers in fibrin does not affect clot
      lysis, the formation of alpha chain polymers has a weak inhibitory effect. Only
      strong cross-linking of fibrin, associated with high molecular weight alpha chain
      polymers and/or gamma chain multimers, results in a moderate inhibition
      fibrinolysis. The formation of fibrin-alpha2AP cross-links has only a weak effect
      on clot lysis, but this effect becomes strong when clot retraction occurs. Under
      these conditions, FXIII prevents alpha2AP being expelled from the clot and makes
      the clot relatively resistant to degradation by plasmin.

PMID- 28761876
TI  - Sustainability of Endovenous Iron Deficiency Anaemia Treatment: Hospital-Based
      Health Technology Assessment in IBD Patients.
AB  - Iron deficiency anaemia (IDA) is the main extraintestinal manifestation affecting
      patients with inflammatory bowel disease (IBD). The Health Technology Assessment
      approach was applied to evaluate the sustainability of intravenous (IV) iron
      formulations in the Italian hospital setting, with particular focus on ferric
      carboxymaltose. Data on the epidemiology of IBD and associated IDA, in addition
      to the efficacy and safety of IV iron formulations currently used in Italy, were
      retrieved from scientific literature. A hospital-based cost-analysis of the
      outpatient delivery of IV iron treatments was performed. Organizational and
      ethical implications were discussed. IDA prevalence in IBD patients varies
      markedly from 9 to 73%. IV iron preparations were proven to have good efficacy
      and safety profiles, and ferric carboxymaltose provided a fast correction of
      haemoglobin and serum ferritin levels in iron-deficient patients. Despite a
      higher price, ferric carboxymaltose would confer a beneficial effect to the
      hospital, in terms of reduced cost related to individual patient management and
      additionally to the patient by reducing the number of infusions and admissions to
      healthcare facilities. Ethically, the evaluation is appropriate due to its
      efficacy and compliance. This assessment supports the introduction of ferric
      carboxymaltose in the Italian outpatient setting.

PMID- 28761877
TI  - Basic Fibroblast Growth Factor-Anchored Multilayered Mesenchymal Cell Sheets
      Accelerate Periosteal Bone Formation.
AB  - Cell-based regenerative therapy has the potential to repair bone injuries or
      large defects that are recalcitrant to conventional treatment methods, including
      drugs and surgery. Here, we developed a multilayered cell-based bone formation
      system using cells coated with fibronectin-gelatin (FN-G) nanofilms. The
      multilayered mesenchymal cells (MLMCs) were formed after two days of culture and
      were shown to express higher levels of BMP-2 and VEGF compared to monolayer
      cultures of MCs. The MLMCs were used as a graft material in combination with a
      fusion protein consisting of basic fibroblast growth factor (bFGF), polycystic
      kidney disease (PKD) domain, and the collagen-binding domain (CBD) of Clostridium
      histolyticum collagenase. In femur sites grafted with the MLMCs, significantly
      higher levels of callus volume and bone mineral content were observed compared to
      the sham controls. The callus volume and bone mineral content were further
      increased in femur sites grafted with bFGF-PKD-CBD/MLMCs. Taken together, these
      results suggest that bFGF-PKD-CBD/MLMCs, which can be simply and rapidly
      generated in vitro, have the potential to promote bone repair when grafted into
      large defect sites.

PMID- 28761879
TI  - Alcohol Consumption Is a Risk Factor for Lower Extremity Arterial Disease in
      Chinese Patients with T2DM.
AB  - OBJECTIVE: To investigate the relationship between alcohol consumption and
      diabetic lower extremity arterial disease (LEAD) in hospitalized patients with
      type 2 diabetes mellitus (T2DM). METHODS: We evaluated 138 hospitalized patients
      with T2DM who consumed alcohol and 833 who did not. We used propensity score
      matching to reduce the confounding bias between groups. Additionally, a logistic
      regression analysis was performed with the matched data to evaluate the LEAD
      risk. RESULTS: In total, 119 pairs of patients who did and did not consume
      alcohol were matched. According to the logistic regression analysis, patients who
      consumed >8 U of alcohol/day had a higher risk of LEAD (odds ratio (OR): 6.35,
      95% confidence interval (CI): 1.78-22.65) than patients who did not consume
      alcohol. Additionally, after adjusting for age, gender, region, occupation,
      smoking status, body mass index, weight change, and duration of diabetes, the OR
      of peripheral artery disease after >20 years of alcohol consumption was 3.48 (95%
      CI: 1.09-11.15). Furthermore, we observed a significant dose-response
      relationship between alcohol consumption and LEAD. CONCLUSIONS: Alcohol
      consumption may be a risk factor of LEAD in patients with T2DM. Patients with
      T2DM should be advised to stop drinking, to prevent the onset of LEAD.

PMID- 28761881
TI  - Considering social accountability in rehabilitation therapy school.

PMID- 28761880
TI  - Therapeutic Effects of Methanol Extract from Euphorbia kansui Radix on Imiquimod
      Induced Psoriasis.
AB  - The roots of Euphorbia kansui, which belong to the family Euphorbiaceae, have
      been used as a traditional medicine for the treatment of various diseases such as
      diabetes, ascites, and leukemia. Recently, it was reported that the methylene
      chloride fraction of E. kansui radix (EKC) regulated the differentiation of Th17
      cells and alleviated the symptoms of Th17-related inflammatory bowel disease.
      Imiquimod (IMQ), a TLR7/8 agonist, has been used to induce psoriasis in a mouse
      model. In this study, we evaluated the effect of EKC in an IMQ-induced psoriasis
      model. EKC effectively inhibited the production of interleukin-17A and interferon
      gamma in vitro. On this basis, EKC was administered to an animal model of
      psoriasis. Acanthosis and the infiltration of inflammatory cells into the dermis
      were significantly reduced by EKC. EKC also inhibited the expression of IL-17A,
      IL-22, IL-23, IL-12, and RAR-related orphan receptor gamma t (RORgammat) in the
      spleen, skin-draining lymph nodes, and the skin. Additionally, EKC inhibited the
      activity of dendritic cells but not that of keratinocytes. In conclusion, EKC
      ameliorated the symptoms of psoriasis through inhibition of Th17 differentiation
      and activation of dendritic cells. These effects are expected to be beneficial in
      the treatment and prevention of psoriasis.

PMID- 28761882
TI  - Evidence-based medicine in pre-clinical years: a study of early introduction and
      usefulness.
AB  - INTRODUCTION: Evidence Based Medicine (EBM) has established itself as a strong
      predictor of future medical practice by medical students. The purpose of this
      study was to determine the effectiveness of EBM in pre-clinical years and reflect
      on self-assessment skill of 4th semester medical students regarding the
      understanding of EBM and its various determinants. METHODS: All of the 4th
      semester (MD4) medical students at the Avalon University of Medical School,
      Curacao who had completed their EBM curriculum were asked to voluntarily
      participate in a cross sectional student survey containing qualitative and
      quantitative questionnaires in a 10-point scale. The students' responses were
      analyzed statistically and the results reported. RESULTS: Twenty-three students
      participated in the survey. 91% of them reported that EBM had helped them to
      better understand research process and 95% believed that EBM was necessary to
      develop clinical skills in the future. 78% of the students agreed that they were
      provided with enough resources for effective implementation of EBM in the
      university. All participants (100%) self reported that they could appraise the
      research articles effectively (mean score 8.26, S.D-1.45). CONCLUSIONS: EBM is an
      integrative and comprehensive way to successfully adopt concepts of acquired
      medical knowledge for effective medical practice. Early introduction of EBM in
      preclinical years proved favorable in students and better equipped them with the
      ability to critically apprehend and appraise new research and innovations in
      medicine for optimal learning experience. There is a definitive need for
      scientific and systematic design of the curriculum for early introduction of EBM
      in pre-clinical years, best suited for the students. The principles should be
      directed towards further research for the effective implementation of EBM to
      enhance clinical skills.

PMID- 28761883
TI  - Evidence-based practice in Physiotherapy curricula: A survey of Indian Health
      Science Universities.
AB  - INTRODUCTION: Evidence-based practice (EBP) is the conscientious, explicit and
      judicious use of the current evidence in clinical decision making. The
      physiotherapy profession has expressed a commitment to the development and use of
      evidence. However, very little is known about the extent to which EBP is
      integrated in physiotherapy curricula in India. The purpose of this study was to
      describe integration of EBP in Indian physiotherapy programs. METHODS: An
      observational study was conducted where a review of curricula of all Health
      Science Universities (HSU) in India, offering an undergraduate (UG) and post
      graduate (PG) degree program in physical therapy was conducted using a data
      abstraction sheet. It gathered data on inclusion of research components of EBP in
      the curricula, content and hours of teaching EBP, and assessment methods. Data
      were analyzed descriptively. RESULTS: Curricula of fifteen HSU offering
      physiotherapy programs were reviewed. Contents relevant to EBP were incorporated
      from the 2nd yr to final year. Common courses included research methodology
      (84.61%), research project (69.23%) and clinical management subjects (57.14%). No
      guidelines were given about adopting EBP in clinical practice. Didactic lectures
      were the mode of teaching (81.81%). Preferred method for assessing research
      projects was viva (44.44%). Ccritical appraisal was least included in the entry
      level education. Contents relevant to all the five steps of EBP were included in
      PG curricula. CONCLUSIONS: Though physiotherapy programs are introducing EBP
      teaching at the entry level, it lacks structured systematic approach and is
      fragmented. There is inadequate emphasis on clinical oriented teaching of EBP and
      assessment methods. Moreover, there is adequate coverage of EBP content in PG
      curricula.

PMID- 28761878
TI  - Characterization, Preparation, and Purification of Marine Bioactive Peptides.
AB  - Marine bioactive peptides, as a source of unique bioactive compounds, are the
      focus of current research. They exert various biological roles, some of the most
      crucial of which are antioxidant activity, antimicrobial activity, anticancer
      activity, antihypertensive activity, anti-inflammatory activity, and so forth,
      and specific characteristics of the bioactivities are described. This review also
      describes various manufacturing techniques for marine bioactive peptides using
      organic synthesis, microwave assisted extraction, chemical hydrolysis, and
      enzymes hydrolysis. Finally, purification of marine bioactive peptides is
      described, including gel or size exclusion chromatography, ion-exchange column
      chromatography, and reversed-phase high-performance liquid chromatography, which
      are aimed at finding a fast, simple, and effective method to obtain the target
      peptides.

PMID- 28761884
TI  - Social Accountable Medical Education: A concept analysis.
AB  - INTRODUCTION: Considering the pervasiveness of social accountable medical
      education concept around the world and the growing trend of literature in this
      regard as well as various interpretations made about this concept, we found it
      necessary to analyze the concept of social accountable medical education.
      METHODS: In this study, the modified version of McKenna's approach to concept
      analysis was used to determine the concept, explain structures and substructures
      and determine the border concepts neighboring and against social accountability
      in medical education. RESULTS: By studying the selected sources,the components of
      the concept were obtained to identify it and express an analytic definition of
      social accountability in medical education system. Then, a model case with all
      attributes of the given concept and the contrary and related concepts were
      mentioned to determine the boundary between the main concept and auxiliary ones.
      CONCLUSION: According to the results of this study in the field of social
      accountability, the detailed and transparent analytical definition of social
      accountable medical education can be used in future studies as well as the
      function and evaluation of medical education system.

PMID- 28761885
TI  - Self- directed learning barriers in a virtual environment: a qualitative study.
AB  - INTRODUCTION: There is a growing trend in online education courses in higher
      education institutes. Previous studies have shown that high levels of self
      direction are essential for successful online learning. The present study aims to
      investigate challenges of and barriers to self-directed virtual-learning among
      postgraduate students of medical sciences. METHOD: 23 postgraduate virtual
      students of medical sciences in Iran, collected through maximum variation
      purposive sampling and semi-structured interviews, served as the sample of this
      study. The collected data were analyzed using the inductive content analysis
      method. RESULTS: Three themes and six sub-themes were identified as barriers to
      self-directed learning in virtual education, including cognitive barriers
      (information overload and lack of focus on learning or mind wondering),
      communication barriers (inadequate coping skills and inadequate writing skills)
      and educational environment barriers (heavy workload and role ambiguity).
      CONCLUSION: By the importance of self-direction in online education, the present
      study results can be used by virtual education planners in the review and design
      of courses, so as to adequately equip students, obviate barriers to self-directed
      virtual education, and ultimately train highly self-directed learners in online
      medical education.

PMID- 28761886
TI  - Balancing power: A grounded theory study on partnership of academic service
      institutes.
AB  - INTRODUCTION: Governments and professional organizations have called for new
      partnerships between health care providers and academics to improve clinical
      education for the benefit of both students and patients. To develop a substantive
      grounded theory on the process of forming academic-service partnerships in
      implementing clinical education, from the perspective of academic and clinical
      nursing staff members and managers working in Iranian settings. METHODS: The
      participants included 15 hospital nurses, nurse managers, nurse educators, and
      educational managers from two central universities and clinical settings from
      2009 to 2012. Data were collected through 30 in-depth, semi-structure interviews
      with the individual participants and then analyzed using the methodology of
      Strauss and Corbin's grounded theory. RESULTS: Utilizing "balancing power" as the
      core variable enabled us to integrate the concepts concerning the partnership
      processes between clinical and educational institutes. Three distinct and
      significant categories emerged to explain the process of partnership: 1)
      divergence, 2) conflict between educational and caring functions, and 3) creation
      of balance between educational and caring functions. CONCLUSIONS: In implementing
      clinical education, partnerships have been formed within a challenging context in
      Iran. Conflict between clinical and educational functions was the main concern of
      both sides of the partnership in forming a collaborative relationship, with our
      findings emphasizing the importance of nursing educators' role in the
      establishment of partnership programs.

PMID- 28761887
TI  - A Study on Capabilities Required In Military Medicine to Develop Modular Training
      Courses: A Qualitative Study.
AB  - INTRODUCTION: The main mission of military medicine in the world is to support
      the health and treatment of the military in relation to issues, risks, injuries
      and diseases that arise due to the specific occupational conditions. The current
      study was carried out with the aim of determining the required skills of military
      physicians to define and determine the required training modules. METHODS: The
      study was a qualitative research. Semi-structured interviews were used to collect
      the data and qualitative content analysis was used to analyze the data. The study
      population included all the professors and experts in the field of military
      medicine and medical sciences at the medical universities of Tehran. Snowball
      sampling technique was used to sample the study participants. RESULTS: Based on
      the results, the required skills of military physicians in 5 categories and 29
      sub- categories were identified; then based on the identified skills, 60 training
      modules at two introductory and advanced levels were determined including 39
      introductory levels and 21 advanced levels. CONCLUSION: We can conclude that some
      of the important skills that military physicians need and can achieved through
      training have not been provided in any educational program and to achieve such
      skills and capabilities, other programs should be developed and modular training
      can be one of them.

PMID- 28761888
TI  - Program evaluation of an Integrated Basic Science Medical Curriculum in Shiraz
      Medical School, Using CIPP Evaluation Model.
AB  - INTRODUCTION: In recent years curriculum reform and integration was done in many
      medical schools. The integrated curriculum is a popular concept all over the
      world. In Shiraz medical school, the reform was initiated by stablishing the
      horizontal basic science integration model and Early Clinical Exposure (ECE) for
      undergraduate medical education. The purpose of this study was to provide the
      required data for the program evaluation of this curriculum for undergraduate
      medical students, using CIPP program evaluation model. METHODS: This study is an
      analytic descriptive and triangulation mixed method study which was carried out
      in Shiraz Medical School in 2012, based on the views of professors of basic
      sciences courses and first and second year medical students. The study evaluated
      the quality of the relationship between basic sciences and clinical courses and
      the method of presenting such courses based on the Context, Input, Process and
      Product (CIPP) model. The tools for collecting data, both quantitatively and
      qualitatively, were some questionnaires, content analysis of portfolios, semi-
      structured interview and brain storming sessions. For quantitative data analysis,
      SPSS software, version 14, was used. RESULTS: In the context evaluation by
      modified DREEM questionnaire, 77.75%of the students believed that this
      educational system encourages them to actively participate in classes. Course
      schedule and atmosphere of class were reported suitable by 87.81% and 83.86% of
      students. In input domain that was measured by a researcher made questionnaire,
      the facilities for education were acceptable except for shortage of cadavers. In
      process evaluation, the quality of integrated modules presentation and Early
      Clinical Exposure (ECE) was good from the students' viewpoint. In product
      evaluation, students' brain storming, students' portfolio and semi-structured
      interview with faculties were done, showing some positive aspects of integration
      and some areas that need improvement. CONCLUSION: The main advantage of assessing
      an educational program based on CIPP evaluation model is that the context, input,
      process and product of the program are viewed and evaluated systematically. This
      will help the educational authorities to make proper decisions based on the
      weaknesses and strengths of the program on its continuation, cessation and
      revision. Based on the results of this study, the integrated basic sciences
      course for undergraduate medical students in Shiraz Medical School is at a
      desirable level. However, attempts to improve or reform some sections and
      continual evaluation of the program and its accreditation seem to be necessary.

PMID- 28761889
TI  - The effect of gender bias on medical students and career choices: a cross
      sectional study.

PMID- 28761890
TI  - Microscopic Colitis After Fecal Microbiota Transplant.
AB  - Microscopic colitis (MC) is an inflammatory condition of the large bowel that is
      associated with chronic, nonbloody diarrhea. Colonoscopy usually demonstrates
      normal mucosa, while tissue biopsy reveals intraepithelial lymphocytes or a
      subepithelial collagen band. Although no specific antibody has been discovered,
      MC is associated with several autoimmune disorders such as celiac disease,
      Hashimoto's thyroiditis, and rheumatoid arthritis. There are only a small number
      of case reports documenting possible hereditary MC cases, but up to 12% of
      patients with MC have a family history of inflammatory bowel disease. Other
      associations include proton pump inhibitor use, cigarette smoking, HLA-DQ2/86,
      and possibly some gastrointestinal infections.

PMID- 28761891
TI  - Ischemic Proctitis Presenting as Rectal Pain and Bloody Diarrhea with No Apparent
      Cause.
AB  - Acute ischemic proctitis is a rare condition usually resulting from severe
      vascular disease or an acute vascular occlusion. The diagnosis is made on
      endoscopy, and mortality rates approach 20-40%. Many patients will require a
      proctectomy as the definitive treatment, especially for gangrenous proctitis. We
      describe an unusual presentation of acute ischemic proctitis in a patient without
      preexisting vascular disease or other precipitants. Furthermore, our patient
      recovered entirely with conservative management and intravenous antibiotics
      alone. We review the existing literature on ischemic proctitis and highlight the
      need for future research to better diagnose and manage this rare condition.

PMID- 28761892
TI  - Hybrid Percutaneous-Endoscopic Treatment for Acute Calculous Cholecystitis in a
      High-Risk Surgical Patient.
AB  - Acute cholecystitis (AC) has long been treated with percutaneous cholecystostomy
      (PC) in patients who are poor surgical candidates, but it is associated with high
      recurrence rate. We report our experience with a hybrid percutaneous-endoscopic
      technique in an elderly patient with AC who had received a PC. In this technique,
      a pediatric endoscope was introduced through the PC opening to the gallbladder,
      and the stones were visualized, fragmented, and extracted using a retrieval
      basket. The patient's AC resolved, and within 2 weeks the PC tube was removed.
      The patient remained asymptomatic at the 6-month and 1-year follow-up visits. We
      believe that if this method is replicated in large scale, it could be an
      effective alternative to cholecystectomy in nonsurgical candidates.

PMID- 28761893
TI  - Gastric Diospyrobezoar Dissolution with Ingestion of Diet Soda and Cellulase
      Enzyme Supplement.
AB  - Diospyrobezoars are a subtype of phytobezoars caused by excessive consumption of
      persimmons, which contain large amounts of tannins. In contrast to phytobezoars,
      diospyrobezoars have a harder consistency than other bezoars, making them more
      difficult to break up both chemically and endoscopically. We have previously
      reported successful dissolution of phytobezoars with diet soda and cellulase. A
      review of the literature found low efficacy of soda in dissolving diospyrobezoars
      compared to other phytobezoars. We report a case of successful dissolution of a
      diospyrobezoar after a failed attempt with diet soda alone.

PMID- 28761894
TI  - Gastric Pneumatosis from Isolated Gastric Calciphylaxis.
AB  - A 58-year-old man with end-stage renal disease presented with hypotension and
      emesis, pale conjunctivae, and a distended abdomen. Labs revealed hypercalcemia
      and leukocytosis. Abdominal imaging showed gastric pneumatosis. Endoscopy
      demonstrated significant hemorrhage and necrosis in the gastric cardia and
      fundus. Biopsies revealed acute ulcerative gastritis and focal intravascular
      calcium phosphate crystals. The patient remained nil per os and was placed on
      omeprazole and sucralfate. Repeat endoscopy demonstrated mucosal healing. Gastric
      calciphylaxis in the setting of gastric pneumatosis is an uncommon finding,
      especially in patients without cutaneous findings.

PMID- 28761895
TI  - Effectiveness of an Intervention for Adherence to Follow-up Recommendations for
      Abnormal Pap Tests in Appalachian Kentucky.
AB  - OBJECTIVE: In collaboration with rural county health departments (CHDs), we
      developed a patient navigation intervention to increase adherence to follow-up
      recommendations for women with abnormal Pap tests. METHODS: Local women were
      recruited, trained and placed in CHDs. Navigation was tailored to the follow-up
      care recommended. Effectiveness was evaluated in a quasi-experimental trial that
      included 13 intervention CHDs and 13 comparison group CHDs. Participants were
      enrolled from September 2008 through July 2010. RESULTS: A total of 478
      participants were enrolled. The proportion that received recommended follow-up
      care was greater in the intervention CHDs (91.6%) than in the comparison group
      CHDs (80.8%) (p = .01). CONCLUSIONS: These results suggest that development of
      policy to promote navigation with rural health care delivery systems has great
      potential to improve patient outcomes.

PMID- 28761896
TI  - Alpha and theta band dynamics related to sentential constraint and word
      expectancy.
AB  - Despite strong evidence for prediction during language comprehension, the
      underlying mechanisms, and the extent to which they are specific to language,
      remain unclear. Re-analyzing an ERP study, we examined responses in the time
      frequency domain to expected and unexpected (but plausible) words in strongly and
      weakly constraining sentences, and found results similar to those reported in
      nonverbal domains. Relative to expected words, unexpected words elicited an
      increase in the theta band (4-7 Hz) in strongly constraining contexts, suggesting
      the involvement of control processes to deal with the consequences of having a
      prediction disconfirmed. Prior to critical word onset, strongly constraining
      sentences exhibited a decrease in the alpha band (8-12 Hz) relative to weakly
      constraining sentences, suggesting that comprehenders can take advantage of
      predictive sentence contexts to prepare for the input. The results suggest that
      the brain recruits domain-general preparation and control mechanisms when making
      and assessing predictions during sentence comprehension.

PMID- 28761898
TI  - Pleural Effusion Caused by Bacillus Calmette-Guerin Immunotherapy for Bladder
      Cancer.
AB  - Intravesical bacillus Calmette Guerin (BCG) instillation has been used as
      immunotherapy for early stage bladder cancer for >40 years. Complications from
      this therapy are rare but may result in a spectrum of infectious sequelae. Here
      we describe the case of an elderly man who presented with a pleural effusion and
      subcutaneous nodule several years after treatment with BCG.

PMID- 28761897
TI  - The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile
      Neutropenia: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Despite reports questioning its efficacy, cefepime remains a first
      line option in febrile neutropenia. We aimed to re-evaluate the role of cefepime
      in this setting. METHODS: We searched the PubMed and EMBASE databases to identify
      randomized comparisons of (1) cefepime vs alternative monotherapy or (2) cefepime
      plus aminoglycoside vs alternative monotherapy plus aminoglycoside, published
      until November 28, 2016. RESULTS: Thirty-two trials, reporting on 5724 patients,
      were included. Clinical efficacy was similar between study arms (P = .698), but
      overall mortality was greater among cefepime-treated patients (risk ratio [RR] =
      1.321; 95% confidence interval [CI], 1.035-1.686; P = .025). Also of note, this
      effect seemed to stem from trials using low-dose (2 grams/12 hours, 100 mg/kg per
      day) cefepime monotherapy (RR = 1.682; 95% CI, 1.038-2.727; P = .035). Cefepime
      was also associated with increased mortality compared with carbapenems (RR =
      1.668; 95% CI, 1.089-2.555; P = .019), a finding possibly influenced by cefepime
      dose, because carbapenems were compared with low-dose cefepime monotherapy in 5
      of 9 trials. Treatment failure in clinically documented infections was also more
      frequent with cefepime (RR = 1.143; 95% CI, 1.004-1.300; P = .043). Toxicity
      related treatment discontinuation was more common among patients that received
      high-dose cefepime (P = .026), whereas low-dose cefepime monotherapy resulted in
      fewer adverse events, compared with alternative monotherapy (P = .009).
      CONCLUSIONS: Cefepime demonstrated increased mortality compared with carbapenems,
      reduced efficacy in clinically documented infections, and higher rates of
      toxicity-related treatment discontinuation. The impact of cefepime dosing on
      these outcomes is important, because low-dose regimens were associated with lower
      toxicity at the expense of higher mortality.

PMID- 28761899
TI  - Efficacy and Safety of Intravenous Peramivir Compared With Oseltamivir in High
      Risk Patients Infected With Influenza A and B Viruses: A Multicenter Randomized
      Controlled Study.
AB  - BACKGROUND: Clinical studies comparing the different neuraminidase inhibitors for
      treatment of at-risk patients with influenza have not been performed. To optimize
      such treatments, we assessed the efficacy and safety of intravenous peramivir
      compared with oral oseltamivir in treating seasonal influenza A or B virus
      infection. METHODS: A multicenter, randomized, controlled clinical trial was
      conducted from December 2012 to May 2014 in high-risk patients infected with
      seasonal influenza. A total of 92 adult inpatients and outpatients with high risk
      factors (HRFs) were treated by either a single intravenous infusion of peramivir
      (600 mg) or oral administration of oseltamivir (75 mg, twice per day for 5 days).
      RESULTS: The median times to clinical stability (time to reach <37 degrees C)
      were 40.0 hours (95% confidence interval [CI] = 23.3-64.5) and 37.8 hours (95% CI
      = 26.3-45.3) in the peramivir and oseltamivir groups, respectively; these values
      did not reveal a significant difference. The virus titer and change of mean total
      symptom scores decreased similarly with both treatments. Results of step-wise
      regression suggested that virus type was a significantly effective prognostic
      factor with respect to illness resolution. Adverse events (AEs) with peramivir
      and oseltamivir occurred in 2.2% (n = 1/46) and 13.0% (n = 6/46) of patients,
      respectively. The severity of AEs was mild in all cases except 2 patients who
      showed pneumonia or COPD aggravation; both were in the oseltamivir group.
      CONCLUSIONS: Intravenous peramivir was effective based on the result of direct
      comparison with oral oseltamivir. Thus our data show that peramivir is a useful
      option for the treatment of influenza-infected patients with HRFs.

PMID- 28761900
TI  - Biphasic Zika Illness With Rash and Joint Pain.
AB  - During the current Zika virus (ZIKV) outbreak, acute symptomatic ZIKV infection
      in adults appears to be a mild-to-moderate, self-limited illness. We present a
      case of ZIKV rash illness that improved and then relapsed without repeat exposure
      to ZIKV. Clinicians should be alert for relapses in patients with ZIKV infection.

PMID- 28761901
TI  - Metagenomic Sequencing of an Echovirus 30 Genome From Cerebrospinal Fluid of a
      Patient With Aseptic Meningitis and Orchitis.
AB  - Enteroviruses cause a wide spectrum of clinical disease. In this study, we
      describe the case of a young man with orchitis and aseptic meningitis who was
      diagnosed with enterovirus infection. Using unbiased "metagenomic" massively
      parallel sequencing, we assembled a near-complete viral genome, the first use of
      this method for full-genome viral sequencing from cerebrospinal fluid. We found
      that the genome belonged to the subgroup echovirus 30, which is a common cause of
      aseptic meningitis but has not been previously reported to cause orchitis.

PMID- 28761902
TI  - Glucocorticoid-associated blood glucose response and MS relapse recovery.
AB  - OBJECTIVE: To determine the relationship between MS relapse recovery and blood
      glucose (BG) response to IV methylprednisolone (IVMP) treatment. METHODS: We
      retrospectively identified 36 patients with MS admitted for IVMP treatment of
      acute relapse who had adequate data to characterize BG response, relapse
      severity, and recovery. The relationship between glucocorticoid-associated
      nonfasting BG (NFBG) and relapse recovery was assessed. RESULTS: Highest recorded
      nonfasting BG (maximum NFBG [maxNFBG]) values were significantly higher in
      patients with MS without relapse recovery compared with those with recovery (271
      +/- 68 vs 209 +/- 48 mg/dL, respectively; p = 0.0045). After adjusting for
      relapse severity, MS patients with maxNFBG below the group median were 6 times
      (OR = 6.01; 95% CI, 1.08-33.40; p = 0.040) more likely to experience relapse
      recovery than those with maxNFBG above the group median. In a multiple regression
      model adjusting for age, sex, and relapse severity, a 1-mg/dL increase in the
      maxNFBG was associated with 4.5% decrease in the probability of recovery (OR =
      0.955; 95% CI, 0.928-0.983; p = 0.002). CONCLUSIONS: These findings suggest that
      higher glucocorticoid-associated NFBG values in acutely relapsing patients with
      MS are associated with diminished probability of recovery. This relationship
      could reflect steroid-associated hyperglycemia and/or insulin resistance, defects
      in non-steroid-associated (e.g., prerelapse) glucose metabolism, or both. This
      study included only those admitted for an MS relapse, and it is this subset of
      patients for whom these findings may be most relevant. A prospective study to
      evaluate glucose regulation and MS relapse recovery in a broader outpatient MS
      population is under way.

PMID- 28761903
TI  - Natalizumab granule cell neuronopathy: FDG-PET in diagnosis and immune
      reconstitution with G-CSF.

PMID- 28761904
TI  - IgLON5 antibody: Neurological accompaniments and outcomes in 20 patients.
AB  - OBJECTIVE: To describe the phenotypes, treatment response, and outcome of IgLON5
      autoimmunity. METHODS: Archived serum and CSF specimens from 367 patients known
      to harbor unclassified antibodies which stained neural synapses diffusely
      (mimicking amphiphysin-IgG) were reevaluated by indirect immunofluorescence assay
      (IFA) using a composite of mouse tissues and recombinant IgLON5-transfected cell
      based assay (CBA, Euroimmun). RESULTS: Available specimens (serum, 25; CSF, 9)
      from 26/367 patients (7%) had identical IFA appearance and robust IgLON5 CBA
      positivity. Clinical information was available for 20/26 patients; 13 were women.
      Median disease-onset age was 62 years (range, 46-75 years). Most patients had
      insidious onset and progression of neurological symptoms affecting movement and
      sleep predominantly. Sleep disorders were sleep-disordered breathing (11) and
      parasomnias (3). Brainstem disorders were gait instability (14), dysphagia (10),
      abnormal eye movements (7), respiratory dysfunction (6), ataxia (5),
      craniocervical dystonia (3), and dysarthria (3). Findings compatible with
      hyperexcitability included myoclonus (3), cramps (3), fasciculations (2), and
      exaggerated startle (2). Neuropsychiatric disorders included cognitive
      dysfunction (6), psychiatric symptoms (5), and seizures (1). Dysautonomia, in 9,
      affected bladder function (7), gastrointestinal motility (3), thermoregulation
      (3), and orthostatic tolerance (1). Just 2 patients had coexisting autoimmune
      disease. Brain MRI findings were nonspecific and CSF was noninflammatory in all
      tested. Seven of 9 immunotherapy-treated patients improved: 6 of those 7 were
      stable at last follow-up. Three untreated patients died. Each IgLON5-IgG subclass
      (1-4) was readily detectable in >=80% of specimens using CBA. CONCLUSIONS: IgLON5
      IgG is diagnostic of a potentially treatable neurological disorder, where
      autoimmune clues are otherwise lacking.

PMID- 28761905
TI  - Frequencies of neuronal autoantibodies in healthy controls: Estimation of disease
      specificity.
AB  - OBJECTIVE: To provide an extensive overview on the prevalence of antibodies
      against neuronal surfaces (neuronal surface antibody [NSAb]) in healthy
      participants and disease controls. METHODS: We searched the PubMed database (1974
      to October 2016) for studies that analyzed frequencies of 22 different NSAbs in
      serum or CSF and included controls. Antibody prevalence was calculated for
      patients with NSAb-mediated disease and controls, including healthy participants,
      and those with neurologic and nonneurologic diseases. Different assays for
      antibody detection were compared. RESULTS: In 309 articles, 743,299 antibody
      tests for 22 NSAbs were performed, including 30,485 tests for 19 NSAbs in healthy
      controls (HCs). Of these, 26,423 (86.7%) were tested with current standard
      methods, usually cell-based assays. Prevalence was very low in HCs (mean 0.23%,
      absent for 9/19 antibodies), and test numbers ranged from 21 to 3,065 per
      antibody. One study reported >1,000 healthy participants, and the others
      contained 21-274 samples. CSF samples were virtually not available from HCs. NSAb
      prevalence was considerably higher (1.5%) in 69,850 disease controls, i.e.,
      patients not initially suspected to have NSAb-mediated diseases. Antibody
      determination in controls using nonstandard assays (such as ELISA) resulted in 6%
      positivity. CONCLUSIONS: NSAbs are rarely found in healthy participants,
      particularly with standard detection methods, suggesting high disease specificity
      and supporting their diagnostic usefulness. Conversely, positive titers in
      atypical patients might point to the still expanding phenotypic spectrum. Future
      studies should include more CSF samples, data from HCs, and experimental evidence
      for antibody pathogenicity.

PMID- 28761906
TI  - MRI evaluation of thalamic volume differentiates MS from common mimics.
AB  - OBJECTIVE: To determine whether MRI evaluation of thalamic volume differentiates
      MS from other disorders that cause MRI white matter abnormalities. METHODS: There
      were 40 study participants: 10 participants with MS without additional
      comorbidities for white matter abnormalities (MS - c); 10 participants with MS
      with additional comorbidities for white matter abnormalities (MS + c); 10
      participants with migraine, MRI white matter abnormalities, and no additional
      comorbidities for white matter abnormalities (Mig - c); and 10 participants
      previously incorrectly diagnosed with MS (Misdx). T1-magnetization-prepared rapid
      gradient-echo and T2-weighted three-dimensional fluid attenuation inversion
      recovery sequences were acquired on a Phillips Achieva d-Stream 3T MRI, and scans
      were randomly ordered and de-identified for a blinded reviewer who performed MRI
      segmentation using LesionTOADS. RESULTS: Mean normalized thalamic volume differed
      among the 4 cohorts (analysis of variance, p = 0.005) and was smaller in the 20
      MS participants compared with the 20 non-MS participants (p < 0.001), smaller in
      MS - c compared with Mig - c (p = 0.03), and smaller in MS + c compared with
      Misdx (p = 0.006). The sensitivity and specificity were both 0.75 for diagnosis
      of MS with a thalamic volume <0.0077. CONCLUSIONS: MRI volumetric evaluation of
      the thalamus, but not other deep gray-matter structures, differentiated MS from
      other diseases that cause white matter abnormalities and are often mistaken for
      MS. Evaluation for thalamic atrophy may improve accuracy for diagnosis of MS as
      an adjunct to additional radiologic criteria. Thalamic volumetric assessment by
      MRI in larger cohorts of patients undergoing evaluation for MS is needed, along
      with the development of automated and easily applied volumetric assessment tools
      for future clinical application. CLASSIFICATION OF EVIDENCE: This study provides
      Class III evidence that MRI evaluation of thalamic volume differentiates MS from
      other diseases that cause white matter abnormalities.

PMID- 28761907
TI  - Feasibility and reproducibility of liver surface nodularity quantification for
      the assessment of liver cirrhosis using CT and MRI.
AB  - PURPOSE: To assess intra-observer, inter-observer and inter-modality (CT vs. MRI)
      reproducibility of liver surface nodularity (LSN) scores measured with software
      used for detection of liver fibrosis. METHODS: This IRB-approved retrospective
      study included patients with both abdominal CT and MRI within 6 months of
      histopathologic sampling. Two independent observers used post-processing software
      to quantify LSN scores on axial non-contrast CT (NCT), axial contrast-enhanced CT
      (CECT), axial T2-weighted (T2W) HASTE, and axial and coronal post-gadoxetic acid
      T1-weighted (T1W) images obtained during the hepatobiliary phase (HBP). Ten
      slices were used to acquire the LSN scores. Intra-observer, inter-observer, and
      inter-modality (CT vs. MRI) reproducibility were assessed with intraclass
      correlation coefficient (ICC) and coefficients of variability (CV). Accuracy for
      detection of cirrhosis was evaluated for each technique. RESULTS: 26 patients
      (M/F 19/7, mean age 57 years), including 7 with cirrhosis (26.9%), were assessed.
      Technical failure occurred with NCT (1/23, 4.3%) and T2 HASTE (8/28, 28.6%).
      Intra-observer reproducibility was excellent for NCT, CECT, axial and coronal T1W
      HBP [ICC >= 0.92, CV <= 8%]. Inter-observer reproducibility was also excellent
      for NCT and CECT (ICC >= 0.95, CV <= 7.3%) and for coronal T1W HBP (ICC = 0.84,
      CV = 5.6%). There was fair to moderate agreement between CT and MRI (ICC 0.20
      0.44). There were significant differences in mean LSN scores between non
      cirrhotic and cirrhotic patients with NCT (2.6 vs. 4.2, p = 0.04) and T1W HBP
      (3.7 vs. 4.6; p = 0.01) images, with AUCs of 0.81 and 0.82, respectively.
      CONCLUSIONS: LSN measurement is highly reproducible with NCT and post-contrast
      T1W HBP on MRI, with different results obtained between CT and MRI.

PMID- 28761908
TI  - Data on the effect of homogenization heat treatments on the cast structure and
      tensile properties of alloy 718Plus in the presence of grain-boundary elements.
AB  - The segregation of the elements during solidification and the direct formation of
      destructive phases such as Laves from the liquid, result in in-homogeneity of the
      cast structure and degradation of mechanical properties. Homogenization heat
      treatment is one of the ways to eliminate destructive Laves from the cast
      structure of superalloys such as 718Plus. The collected data presents the effect
      of homogenization treatment conditions on the cast structure, hardness, and
      tensile properties of the alloy 718Plus in the presence of boron and zirconium
      additives. For this purpose, five alloys with different contents of boron and
      zirconium were cast by VIM/VAR process and then were homogenized at various
      conditions. The microstructural investigation by OM and SEM and phase analysis by
      XRD were done and then hardness and tensile tests were performed on the
      homogenized alloys.

PMID- 28761909
TI  - Correcting names of bacteria deposited in National Microbial Repositories: an
      analysed sequence data necessary for taxonomic re-categorization of misclassified
      bacteria-ONE example, genus Lysinibacillus.
AB  - A report on 16S rRNA gene sequence re-analysis and digitalization is presented
      using Lysinibacillus species (one example) deposited in National Microbial
      Repositories in India. Lysinibacillus species 16S rRNA gene sequences were
      digitalized to provide quick response (QR) codes, Chaose Game Representation
      (CGR) and Frequency of Chaose Game Representation (FCGR). GC percentage,
      phylogenetic analysis, and principal component analysis (PCA) are tools used for
      the differentiation and reclassification of the strains under investigation. The
      seven reasons supporting the statements made by us as misclassified
      Lysinibacillus species deposited in National Microbial Depositories are given in
      this paper. Based on seven reasons, bacteria deposited in National Microbial
      Repositories such as Lysinibacillus and many other needs reanalyses for their
      exact identity. Leaves of identity with type strains of related species shows
      difference 2 to 8 % suggesting that reclassification is needed to correctly
      assign species names to the analyzed Lysinibacillus strains available in National
      Microbial Repositories.

PMID- 28761910
TI  - Optical properties and impedance spectroscopy analyses for microscale Si pillar
      solar cells.
AB  - In this data article, optical properties and impedance spectroscopy analyses were
      applied for the 5 MUm-height pillar Si solar cells to analyzed the insight of the
      Si geometric effect (Yadav et al., 2017) [1]. The surface reflectance data
      measured for all Si pillar samples (Fixed height of 5 MUm with varying width and
      period. Geometric features of Si pillars are summarized in Table 1) are
      presented. Statistical data after analysis are summarized in the table, to
      profile the integrated reflectance quantitatively. Impedance spectroscopy
      analyses of all the samples were performed to demonstrate the bias-dependent
      space charge region. Mott-Schottky investigation shows the enhancement of built
      in potential values due to the pillar structures.

PMID- 28761911
TI  - Dataset on child nutritional status and its socioeconomic determinants in Nonno
      District, Ethiopia.
AB  - This data article presents child nutritional status and its socioeconomic
      determinants in Ethiopia with special reference to Nonno District, Oromia Region.
      As recommended by WHO (2006) [1], the nutritional status in this data article is
      based on three indices (height-for-age, weight-for-height and weight-for-age) for
      the children in this survey. The data was obtained from four hundred eight (408)
      households selected by using simple random sampling procedure. The data article
      shows that the overall prevalence of child malnutrition in the community was high
      with 46.3% of the children stunted, 41.9% underweight and 11.5% wasted. Moreover,
      the dataset presents family size, parental education, wealth status of the
      household, preceding birth interval, antenatal care (ANC) attendance, disease and
      sanitation are vital determinants of child malnutrition in the area.

PMID- 28761912
TI  - Risk factors accelerating hypothyroidism in pregnant women referred to health
      centers in Abadan, Iran.
AB  - The present work contains data obtained during the analysis of pregnant women
      referred to Abadan Health Centers Organization (Abadan HCO) with confirmed acute
      hypothyroidism diagnosis. From among all pregnant women referred to Abadan HCO,
      600 were chosen consisting of 120 pregnant women from each of the health centers
      in quintuple areas. In this paper, the effects of family history, occupation,
      death, abortion, type of diabetes, smoking, lithium consumption, allergy,
      radiotherapy, ovarian cysts (OC) and oral contraceptive pills (OCP) consumption
      have been studied (Yassaee et al., 2014) [1]. After completion of the
      questionnaires by the patients, the obtained coded data were fed into ECSELL
      software. Statistical analysis of the data was carried out using Special Package
      for Social Sciences version 16 (SPSS 16).

PMID- 28761913
TI  - Zoning of heavy metal concentrations including Cd, Pb and As in agricultural
      soils of Aghili plain, Khuzestan province, Iran.
AB  - Soil is an important component of life cycle affecting agriculture and food
      crops. Quality of soil resources is defined according to their potential impact
      on human health by exposure of harmful constituents through the food chain. Heavy
      metals especially As, Pb and Cd are among the most hazardous elements which could
      be released to the top soil through different wastewaters, fertilizers,
      herbicides and etc. In this research Aghili plain in Khuzestan province, Iran was
      selected as a total of 54 samples were prepared based on a systematic gridding
      procedure. Selected heavy metals concentrations were analyzed by inductively
      coupled plasma mass spectrometry (ICP-MS) and then zoning was performed using
      kriging method. Pollution level was assessed through single factor indices and
      pollution load index. A separate map dealing with each heavy metal was prepared
      to present the distribution of heavy metal in Aghili plain. In all samples the
      heavy metals concentrations were followed the bellow trend: Pb>As>Cd.
      Furthermore, based on the PLI, all stations were categorized as moderately to
      highly polluted sites (1<PLI<4). Due to toxic effects of mentioned heavy metal
      for human health, furture monitoring, some control measures and remedial actions
      should be undertaken in the study area.

PMID- 28761914
TI  - Kinematic and EMG data during underwater dolphin kick change while synchronizing
      with or without synchronization of kick frequency with the beat of a metronome.
AB  - We investigated the effects of synchronizing kick frequency with the beat of a
      metronome on kinematic and electromyographic (EMG) parameters during the
      underwater dolphin kick as a pilot study related to the research that entitled
      "Effect of increased kick frequency on propelling efficiency and muscular co
      activation during underwater dolphin kick" (Yamakawa et al., 2017) [1]. Seven
      collegiate female swimmers participated in this experiment. The participants
      conducted two underwater dolphin kick trials: swimming freely at maximum effort,
      and swimming while synchronizing the kick frequency of maximum effort with the
      beat of a metronome. The kinematic parameters during the underwater dolphin kick
      were calculated by 2-D motion analysis, and surface electromyographic
      measurements were taken from six muscles (rectus abdominis, erector spinae,
      rectus femoris, biceps femoris, tibialis anterior, and gastrocnemius). The
      results revealed no significant differences in the kinematic and EMG parameters
      between trials of the two swimming techniques. Therefore, the action of
      synchronizing the kick frequency with the beat of a metronome did not affect
      movement or muscle activity during the underwater dolphin kick in this
      experiment.

PMID- 28761916
TI  - Re: An unusual migratory polycyclic eruption after administration of
      prostaglandin E in a neonate.

PMID- 28761915
TI  - Data for proteome analysis of Bacillus lehensis G1 in starch-containing medium.
AB  - Bacillus lehensis G1 is a cyclodextrin glucanotransferase (CGTase) producer,
      which can degrade starch into cyclodextrin. Here, we present the proteomics data
      of B. lehensis cultured in starch-containing medium, which is related to the
      article "Proteome-based identification of signal peptides for improved secretion
      of recombinant cyclomaltodextrin glucanotransferase in Escherichia coli" (Ling
      et. al, in press). This dataset was generated to better understand the secretion
      of proteins involved in starch utilization for bacterial sustained growth. A 2-DE
      proteomic technique was used and the proteins were tryptically digested followed
      by detection using MALDI-TOF/TOF. Proteins were classified into functional groups
      using the information available in SubtiList webserver
      (http://genolist.pasteur.fr/SubtiList/).

PMID- 28761917
TI  - Dermatitis herpetiformis with fibrillar IgA deposition and unusual histologic
      findings.

PMID- 28761918
TI  - Systemic contact dermatitis to a surgical implant presenting as red decorative
      tattoo reaction.

PMID- 28761919
TI  - Pink nodule accompanied with clustered yellow globules at the periphery.

PMID- 28761920
TI  - Sorafenib-asssociated hand-foot syndrome treated with topical calcipotriol.

PMID- 28761921
TI  - A possible association between mycosis fungoides and Muir-Torre syndrome: Two
      disorders with microsatellite instability.

PMID- 28761922
TI  - Parasitic botfly infection of a child in central Virginia.

PMID- 28761923
TI  - Exploring the relationship between natural killer cells and cutaneous squamous
      cell carcinoma development.

PMID- 28761924
TI  - Secondary uterine carcinosarcoma after concurrent chemoradiotherapy for cervical
      cancer: Case reports.
AB  - *Secondary uterine sarcomas occur in < 1% of patients treated with
      CCRT.*Secondary uterine sarcomas can occur > 5 years from CCRT.*The median
      survival period from the secondary tumor occurrence was only 4 months.*All our
      patients had heterologous carcinosarcoma of the uterine corpus.

PMID- 28761925
TI  - Recurrent atypical polypoid adenomyoma and pregnancy: A new conservative approach
      with levonorgestrel-releasing intrauterine system.
AB  - *Levonorgestrel IUD was effective in treatment of recurrent APA.*No side effects
      were reported.*No impairments on a subsequent pregnancy were reported.

PMID- 28761926
TI  - Amyloid beta-associated cognitive decline in the absence of clinical disease
      progression and systemic illness.
AB  - INTRODUCTION: High levels of amyloid beta (Abeta) are associated with cognitive
      decline in cognitively normal (CN) older adults. This study investigated the
      nature of cognitive decline in healthy individuals who did not progress to mild
      cognitive impairment or dementia. METHOD: Cognition was measured over 72 months
      and compared between low (Abeta-) and high (Abeta+) CN older adults (n = 335) who
      did not progress to mild cognitive impairment or dementia and who remained free
      of severe or uncontrolled systemic illness. RESULTS: Compared to the Abeta-
      group, the Abeta+ group showed no cognitive impairment at baseline but showed
      substantial decline in verbal learning, episodic memory, and attention over 72
      months. DISCUSSION: Moderate cognitive decline, particularly for learning and
      memory, was associated with Abeta+ in CN older adults in the absence of clinical
      disease progression and uncontrolled or serious comorbid illness.

PMID- 28761928
TI  - Familiarity deficits in cognitively normal aging individuals with APOE epsilon4:
      A follow-up investigation of medial temporal lobe structural correlates.
AB  - INTRODUCTION: The apolipoprotein E epsilon4 (APOE epsilon4) allele is a well
      documented risk factor for Alzheimer's disease (AD). Accordingly, aging
      individuals carrying one or more epsilon4 alleles are at considerably greater
      risk of developing AD over time. In an effort to characterize early cognitive
      manifestations of AD, we previously outlined selective deficits in familiarity
      based recognition in otherwise asymptomatic carriers of the APOE epsilon4 allele
      (Schoemaker et al., 2016). In this follow-up report, we aimed to explore the
      neural correlates of this selective cognitive impairment. METHODS: For this
      purpose, within the same population and using high-resolution structural
      neuroimaging, we explored relationships between volumes of the hippocampus,
      entorhinal, and perirhinal cortices and performance in recollection and
      familiarity. RESULTS: Overall, our results revealed significant positive
      relationships between familiarity performance and volumes of the perirhinal and
      entorhinal cortices in aging individuals with APOE epsilon4. In APOE epsilon4
      carriers, a positive correlation between recollection performance and hippocampal
      volume was also found. In contrast, no correlation reached statistical
      significance in the group of noncarriers. CONCLUSION: These findings suggest that
      familiarity performance might be a useful marker of the integrity of the rhinal
      cortex, especially in populations at risk of AD.

PMID- 28761927
TI  - Body mass index in midlife and dementia: Systematic review and meta-regression
      analysis of 589,649 men and women followed in longitudinal studies.
AB  - INTRODUCTION: We conducted a meta-analysis of the conflicting epidemiologic
      evidence on the association between midlife body mass index (BMI) and dementia.
      METHODS: We searched standard databases to identify prospective, population-based
      studies of dementia risk by midlife underweight, overweight, and obesity. We
      performed random-effects meta-analyses and meta-regressions of adjusted relative
      risk (RR) estimates and formally explored between-study heterogeneity. RESULTS:
      We included 19 studies on 589,649 participants (2040 incident dementia cases)
      followed up for up to 42 years. Midlife (age 35 to 65 years) obesity (BMI >= 30)
      (RR, 1.33; 95% confidence interval [CI], 1.08-1.63), but not overweight (25 < BMI
      < 30) (RR, 1.07; 95% CI, 0.96-1.20), was associated with dementia in late life.
      The association with midlife underweight (RR, 1.39; 95% CI, 1.13-1.70) was
      potentially driven by residual confounding (P from meta-regression = .004),
      selection (P = .046), and information bias (P = .007). DISCUSSION: Obesity in
      midlife increases the risk of dementia. The association between underweight and
      dementia remains controversial.

PMID- 28761929
TI  - Validation of the XDP-MDSP rating scale for the evaluation of patients with X
      linked dystonia-parkinsonism.
AB  - X-linked dystonia-parkinsonism(XDP) is a neurodegenerative disorder endemic to
      the Philippines. A rating scale was developed by the authors under the guidance
      of the Movement Disorder Society of the Philippines (MDSP) to assess XDP severity
      and progression, functional impact, and response to treatment in future clinical
      trials. Our main objective was to validate our new scale, the XDP-MDSP scale. The
      initial validation process included pragmatic testing to XDP patients followed by
      a modified Delphi procedure with an international advisory panel of dystonia,
      parkinsonism and scale development experts. Pearson correlation was used to
      assess construct validity of our new scale versus the assess construct validity
      of our new scale versus standard dystonia, parkinsonism, non-motor and functional
      scales; and also to assess divergent validity against behavioral and cognitive
      scales. The 37-item XDP-MDSP scale has five parts: I-dystonia, II-parkinsonism,
      III-non-motor features, IV-ADL, and V-global impression. After initial
      validation, the scale was administered to 204 XDP patients. Inter-domain
      correlation for the first four parts was acceptable. The correlation between
      these domains and the global rating was slightly lower. Correlations between
      Parts I, II, III, and IV versus standard dystonia, parkinsonism, non-motor and
      functional scales were acceptable with values ranging from 0.323 to 0.428. For
      divergent validity, a significant correlation was seen with behavioral scales. No
      significant correlation was noted with the cognitive scale. The proposed XDP-MDSP
      scale is internally valid but the global rating subscale may need to be modified
      or eliminated. While there is convergent validity, divergent validation was
      successful only on cognitive and not behavioral scales. The frequent co
      occurrence of anxiety and depression, and its effect on the motor and functional
      state, may explain this finding.

PMID- 28761931
TI  - UNC5C variants are associated with cerebral amyloid angiopathy.
AB  - OBJECTIVE: To determine whether common genetic variants in UNC5C, a recently
      identified late-onset Alzheimer disease (LOAD) dementia susceptibility gene, are
      associated with AD susceptibility or AD-related clinical/pathologic phenotypes.
      METHODS: We used data from deceased individuals of European descent who
      participated in the Religious Orders Study or the Rush Memory and Aging Project
      (n = 1,288). We examined whether there were associations between single
      nucleotide polymorphisms (SNPs) within +/-100 kb of the UNC5C gene and a
      diagnosis of AD dementia, global cognitive decline, a pathologic diagnosis of AD,
      beta-amyloid load, neuritic plaque count, diffuse plaque count, paired helical
      filament tau density, neurofibrillary tangle count, and cerebral amyloid
      angiopathy (CAA) score. We also evaluated the relation of the CAA-associated
      variant and dorsolateral prefrontal cortex (DLPFC) UNC5C RNA expression.
      Secondary analyses were performed to examine the interaction of the CAA
      associated SNP and known genetic risk factors of CAA as well as the association
      of the SNP with other cerebrovascular pathologies. RESULTS: A set of UNC5C SNPs
      tagged by rs28660566T was associated with a higher CAA score (p = 2.3 * 10-6):
      each additional rs28660566T allele was associated with a 0.60 point higher CAA
      score, which is equivalent to approximately 75% of the higher CAA score
      associated with each allele of APOE epsilon4. rs28660566T was weakly associated
      with lower UNC5C expression in the human DLPFC (p = 0.036). Moreover, rs28660566T
      had a synergistic interaction with APOE epsilon4 on their association with higher
      CAA severity (p = 0.027) and was associated with more severe arteriolosclerosis
      (p = 0.0065). CONCLUSIONS: Targeted analysis of the UNC5C region uncovered a set
      of SNPs associated with CAA.

PMID- 28761930
TI  - Prevalence of spinocerebellar ataxia 36 in a US population.
AB  - OBJECTIVE: To assess the prevalence and clinical features of individuals affected
      by spinocerebellar ataxia 36 (SCA36) at a large tertiary referral center in the
      United States. METHODS: A total of 577 patients with undiagnosed sporadic or
      familial cerebellar ataxia comprehensively evaluated at a tertiary referral
      ataxia center were molecularly evaluated for SCA36. Repeat primed PCR and
      fragment analysis were used to screen for the presence of a repeat expansion in
      the NOP56 gene. RESULTS: Fragment analysis of triplet repeat primed PCR products
      identified a GGCCTG hexanucleotide repeat expansion in intron 1 of NOP56 in 4
      index cases. These 4 SCA36-positive families comprised 2 distinct ethnic groups:
      white (European) (2) and Asian (Japanese [1] and Vietnamese [1]). Individuals
      affected by SCA36 exhibited typical clinical features with gait ataxia and age at
      onset ranging between 35 and 50 years. Patients also suffered from ataxic or
      spastic limbs, altered reflexes, abnormal ocular movement, and cognitive
      impairment. CONCLUSIONS: In a US population, SCA36 was observed to be a rare
      disorder, accounting for 0.7% (4/577 index cases) of disease in a large
      undiagnosed ataxia cohort.

PMID- 28761932
TI  - Parasite Microbiome Project: Systematic Investigation of Microbiome Dynamics
      within and across Parasite-Host Interactions.
AB  - Understanding how microbiomes affect host resistance, parasite virulence, and
      parasite-associated diseases requires a collaborative effort between
      parasitologists, microbial ecologists, virologists, and immunologists. We hereby
      propose the Parasite Microbiome Project to bring together researchers with
      complementary expertise and to study the role of microbes in host-parasite
      interactions. Data from the Parasite Microbiome Project will help identify the
      mechanisms driving microbiome variation in parasites and infected hosts and how
      that variation is associated with the ecology and evolution of parasites and
      their disease outcomes. This is a call to arms to prevent fragmented research
      endeavors, encourage best practices in experimental approaches, and allow
      reliable comparative analyses across model systems. It is also an invitation to
      foundations and national funding agencies to propel the field of parasitology
      into the microbiome/metagenomic era.

PMID- 28761933
TI  - Insights into Butyrate Production in a Controlled Fermentation System via Gene
      Predictions.
AB  - Butyrate is a common fatty acid produced in important fermentative systems, such
      as the human/animal gut and other H2 production systems. Despite its importance,
      there is little information on the partnerships between butyrate producers and
      other bacteria. The objective of this work was to uncover butyrate-producing
      microbial communities and possible metabolic routes in a controlled fermentation
      system aimed at butyrate production. The butyrogenic reactor was operated at 37
      degrees C and pH 5.5 with a hydraulic retention time of 31 h and a low hydrogen
      partial pressure (PH2). High-throughput sequencing and metagenome functional
      prediction from 16S rRNA data showed that butyrate production pathways and
      microbial communities were different during batch (closed) and continuous-mode
      operation. Lactobacillaceae, Lachnospiraceae, and Enterococcaceae were the most
      abundant phylotypes in the closed system without PH2 control, whereas
      Prevotellaceae, Ruminococcaceae, and Actinomycetaceae were the most abundant
      phylotypes under continuous operation at low PH2. Putative butyrate producers
      identified in our system were from Prevotellaceae, Clostridiaceae,
      Ruminococcaceae, and Lactobacillaceae. Metagenome prediction analysis suggests
      that nonbutyrogenic microorganisms influenced butyrate production by generating
      butyrate precursors such as acetate, lactate, and succinate. 16S rRNA gene
      analysis suggested that, in the reactor, a partnership between identified
      butyrogenic microorganisms and succinate (i.e., Actinomycetaceae), acetate (i.e.,
      Ruminococcaceae and Actinomycetaceae), and lactate producers (i.e.,
      Ruminococcaceae and Lactobacillaceae) took place under continuous-flow operation
      at low PH2. IMPORTANCE This study demonstrates how bioinformatics tools, such as
      metagenome functional prediction from 16S rRNA genes, can help understand
      biological systems and reveal microbial interactions in controlled systems (e.g.,
      bioreactors). Results obtained from controlled systems are easier to interpret
      than those from human/animal studies because observed changes may be specifically
      attributed to the design conditions imposed on the system. Bioinformatics
      analysis allowed us to identify potential butyrogenic phylotypes and associated
      butyrate metabolism pathways when we systematically varied the PH2 in a carefully
      controlled fermentation system. Our insights may be adapted to butyrate
      production studies in biohydrogen systems and gut models, since butyrate is a
      main product and a crucial fatty acid in human/animal colon health.

PMID- 28761934
TI  - Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap
      of Secreted Small Peptidic Molecules.
AB  - Recent research indicates that the human microbiota play key roles in maintaining
      health by providing essential nutrients, providing immune education, and
      preventing pathogen expansion. Processes underlying the transition from a healthy
      human microbiome to a disease-associated microbiome are poorly understood,
      partially because of the potential influences from a wide diversity of bacterium
      derived compounds that are illy defined. Here, we present the analysis of
      peptidic small molecules (SMs) secreted from bacteria and viewed from a temporal
      perspective. Through comparative analysis of mass spectral profiles from a
      collection of cultured oral isolates and an established in vitro multispecies
      oral community, we found that the production of SMs both delineates a temporal
      expression pattern and allows discrimination between bacterial isolates at the
      species level. Importantly, the majority of the identified molecules were of
      unknown identity, and only ~2.2% could be annotated and classified. The catalogue
      of bacterially produced SMs we obtained in this study reveals an undiscovered
      molecular world for which compound isolation and ecosystem testing will
      facilitate a better understanding of their roles in human health and disease.
      IMPORTANCE Metabolomics is the ultimate tool for studies of microbial functions
      under any specific set of environmental conditions (D. S. Wishart, Nat Rev Drug
      Discov 45:473-484, 2016, https://doi.org/10.1038/nrd.2016.32). This is a great
      advance over studying genes alone, which only inform about metabolic potential.
      Approximately 25,000 compounds have been chemically characterized thus far;
      however, the richness of metabolites such as SMs has been estimated to be as high
      as 1 * 1030 in the biosphere (K. Garber, Nat Biotechnol 33:228-231, 2015,
      https://doi.org/10.1038/nbt.3161). Our classical, one-at-a-time activity-guided
      approach to compound identification continues to find the same known compounds
      and is also incredibly tedious, which represents a major bottleneck for global SM
      identification. These challenges have prompted new developments of databases and
      analysis tools that provide putative classifications of SMs by mass spectral
      alignments to already characterized tandem mass spectrometry spectra and
      databases containing structural information (e.g., PubChem and AntiMarin). In
      this study, we assessed secreted peptidic SMs (PSMs) from 27 oral bacterial
      isolates and a complex oral in vitro biofilm community of >100 species by using
      the Global Natural Products Social molecular Networking and the DEREPLICATOR
      infrastructures, which are methodologies that allow automated and putative
      annotation of PSMs. These approaches enabled the identification of an untapped
      resource of PSMs from oral bacteria showing species-unique patterns of secretion
      with putative matches to known bioactive compounds.

PMID- 28761935
TI  - The Skin Microbiome of Cohabiting Couples.
AB  - Distinct microbial communities inhabit individuals as part of the human skin
      microbiome and are continually shed to the surrounding environment. Microbial
      communities from 17 skin sites of 10 sexually active cohabiting couples (20
      individuals) were sampled to test whether cohabitation impacts an individual's
      skin microbiome, leading to shared skin microbiota among partner pairs. Amplified
      16S rRNA genes of bacteria and archaea from a total of 340 skin swabs were
      analyzed by high-throughput sequencing, and the results demonstrated that
      cohabitation was significantly associated with microbial community composition,
      although this association was greatly exceeded by characteristics of body
      location and individuality. Random forest modeling demonstrated that the partners
      could be predicted 86% of the time (P < 0.001) based on their skin microbiome
      profiles, which was always greater than combinations of incorrectly matched
      partners. Cohabiting couples had the most similar overall microbial skin
      communities on their feet, according to Bray-Curtis distances. In contrast, thigh
      microbial communities were strongly associated with biological sex rather than
      cohabiting partner. Additional factors that were associated with the skin
      microbiome of specific body locations included the use of skin care products, pet
      ownership, allergies, and alcohol consumption. These baseline data identified
      links between the skin microbiome and daily interactions among cohabiting
      individuals, adding to known factors that shape the human microbiome and, by
      extension, its relation to human health. IMPORTANCE Our work characterizes the
      influence of cohabitation as a factor influencing the composition of the skin
      microbiome. Although the body site and sampled individual were stronger
      influences than other factors collected as metadata in this study, we show that
      modeling of detected microbial taxa can help with correct identifications of
      cohabiting partners based on skin microbiome profiles using machine learning
      approaches. These results show that a cohabiting partner can significantly
      influence our microbiota. Follow-up studies will be important for investigating
      the implications of shared microbiota on dermatological health and the
      contributions of cohabiting parents to the microbiome profiles of their infants.

PMID- 28761937
TI  - Allostatic breakdown of cascading homeostat systems: A computational approach.
AB  - Homeostasis posits that physiological systems compensate setpoint deviations in
      an attempt to maintain a state of internal constancy. Allostasis, on the other
      hand, suggests that physiological regulation is more appropriately described by
      predictive modulatory actions that, by adjusting setpoints, anticipate and react
      to changes in internal and external demand. In other words, "maintaining
      stability through change." The allostatic perspective enabled the rationalization
      of predictive and reactive homeostasis. While the latter reflects external
      perturbations, the former refers to systemic adaptation in response to
      anticipated changes - not necessarily related to unexpected external
      disturbances. Therefore, the concept of allostasis accounts also for adaptation
      to circadian variations (seasonal, circannual or other predictive variability)
      and interprets the system's adaptation of its setpoints not as reactive/subnormal
      adjustments, but rather as a proper response. Therefore, systemic entrainment to
      periodic demands is handled by predicting and implementing setpoint changes.
      Given the important role of circadian variability and regulation in maintaining
      health, and the loss of circadian entrainment as a predisposing factor and sequel
      of stress, we elaborate on an allostasis model which demonstrates the ability of
      the systems to adapt to circadian demands and quantifies the deteriorative
      natural wear and tear of a system constantly adapting, i.e. the irreversible
      damage and its consequences on system function and overall survival. While
      developing a system of cascaded nature, we demonstrate the importance of phase
      coordination and the implications of maintaining proper phase relations. The
      disruption of these relations is a hallmark of circadian disruption, a
      predisposing factor to increased vulnerability and/or a sequel to chronic stress.

PMID- 28761936
TI  - Clostridium difficile Colonizes Alternative Nutrient Niches during Infection
      across Distinct Murine Gut Microbiomes.
AB  - Clostridium difficile is the largest single cause of hospital-acquired infection
      in the United States. A major risk factor for Clostridium difficile infection
      (CDI) is prior exposure to antibiotics, as they disrupt the gut bacterial
      community which protects from C. difficile colonization. Multiple antibiotic
      classes have been associated with CDI susceptibility, many leading to distinct
      community structures stemming from variation in bacterial targets of action.
      These community structures present separate metabolic challenges to C. difficile.
      Therefore, we hypothesized that the pathogen adapts its physiology to the
      nutrients within different gut environments. Utilizing an in vivo CDI model, we
      demonstrated that C. difficile highly colonized ceca of mice pretreated with any
      of three antibiotics from distinct classes. Levels of C. difficile spore
      formation and toxin activity varied between animals based on the antibiotic
      pretreatment. These physiologic processes in C. difficile are partially regulated
      by environmental nutrient concentrations. To investigate metabolic responses of
      the bacterium in vivo, we performed transcriptomic analysis of C. difficile from
      ceca of infected mice across pretreatments. This revealed heterogeneous
      expression in numerous catabolic pathways for diverse growth substrates. To
      assess which resources C. difficile exploited, we developed a genome-scale
      metabolic model with a transcriptome-enabled metabolite scoring algorithm
      integrating network architecture. This platform identified nutrients that C.
      difficile used preferentially between pretreatments, which were validated through
      untargeted mass spectrometry of each microbiome. Our results supported the
      hypothesis that C. difficile inhabits alternative nutrient niches across cecal
      microbiomes with increased preference for nitrogen-containing carbon sources,
      particularly Stickland fermentation substrates and host-derived glycans.
      IMPORTANCE Infection by the bacterium Clostridium difficile causes an
      inflammatory diarrheal disease which can become life threatening and has grown to
      be the most prevalent nosocomial infection. Susceptibility to C. difficile
      infection is strongly associated with previous antibiotic treatment, which
      disrupts the gut microbiota and reduces its ability to prevent colonization. In
      this study, we demonstrated that C. difficile altered pathogenesis between hosts
      pretreated with antibiotics from separate classes and exploited different
      nutrient sources across these environments. Our metabolite score calculation also
      provides a platform to study nutrient requirements of pathogens during an
      infection. Our results suggest that C. difficile colonization resistance is
      mediated by multiple groups of bacteria competing for several subsets of
      nutrients and could explain why total reintroduction of competitors through fecal
      microbial transplant currently is the most effective treatment for recurrent CDI.
      This work could ultimately contribute to the identification of targeted, context
      dependent measures that prevent or reduce C. difficile colonization, including
      pre- and probiotic therapies.

PMID- 28761939
TI  - Error estimation, validity and best practice guidelines for quantifying
      coalescence frequency during emulsification using the step-down technique.
AB  - Coalescence during emulsification has a significant effect on the outcome of the
      process, especially for the high volume fractions of disperse phase common in
      food and pharmaceutical processing. Controlling emulsification requires that the
      extent of coalescence during different conditions can be quantified. The step
      down technique is the most commonly used method for measuring coalescence
      frequency during emulsification. However, the validity of the method has been
      questioned. No in-depth theoretical validation or best practice guidelines have
      been provided for the step-down technique, or for any of the suggested
      alternative methods. This contribution derives error estimates for three non
      idealities present in every step-down experiment: i) limited sampling rate, ii)
      non-instantaneous step-down and iii) residual fragmentation after the step. It is
      concluded that all three factors give rise to systematic errors in estimating
      coalescence rate. However, by carefully choosing experimental settings, the
      errors can be kept small. The method, thus, remains suitable for many conditions.
      Best practice guidelines for applying the method are given, both generally, and
      more specifically for stirred tank oil-in-water emulsification.

PMID- 28761938
TI  - Down-regulation of hK7 in the sera of breast cancer and benign breast disease
      patients.
AB  - INTRODUCTION: Breast cancer is known as a leading cause of cancer-related death
      among women all over the world. Biomarkers facilitate diagnosis at the earliest
      possible stage and better prognosis of the disease. Hence, may help to improve
      the overall survival rate among breast cancer patients. To find a better
      diagnostic/prognostic marker we evaluated human tissue kallikrein 7 (hK7) as
      biomarker of breast cancer. hK7 is a secreted serine protease having chymotrypsin
      like activity. Serum hK7 is known to have aberrant expression in ovarian and
      prostate cancer but has not been yet studied in breast cancer. However, the
      expression level of KLK7 mRNA in breast cancer tissues has been indicated as a
      better prognostic marker for the unfavorable prognosis of breast carcinoma.
      MATERIALS AND METHODS: In this study a time-resolved immunofluorometric indirect
      back titration ELISA (bt-ELISA) was employed for the quantification of hK7 in
      serum of breast cancer patients (n = 47), benign breast disease patients (n = 13)
      alongwith the gender and age group specific controls (n = 99). RESULTS: hK7 was
      significantly down-regulated in the sera of female breast cancer patients (p <
      0.0001; Mean 0.704 +/- 0.533 MUg/L) and benign breast disease patients (p =
      0.0008; Mean 0.651 +/- 0.584) as compared to normal controls (Mean 1.665 +/-
      1.174 MUg/L). CONCLUSIONS: Down regulation of hK7 suggests the possible role of
      this protein in natural course of breast cancer and benign breast diseases. Study
      should be extended on large-scale to confirm the potential of hK7 as biomarker of
      breast cancer.

PMID- 28761940
TI  - Management of Ankylotic Root Resorption Following Dental Trauma: A Short Review
      and Proposal of a Treatment Protocol.
AB  - Ankylotic root resorption is a serious complication following traumatic dental
      injuries. The aetiology of root resorption includes acute injury to the cementum
      and periodontal ligament, and subsequent biological processes that propagate the
      harm. The aim of the present paper is to present a structured treatment protocol
      for teeth that have experienced trauma and are at risk of developing ankylotic
      root resorption, followed by a decoronation protocol for situations in which
      ankylotic root resorption developed. This protocol provides a structured road map
      from the primary dental trauma, through the initial development of ankylosis
      detected radiographically, to the clinical manifestation that results in
      significant infra-occlusion. The current protocol integrates the best available
      evidence from the literature and from published guidelines. Ample contradictory
      data, which mainly consists of case reports related to the treatment of ankylotic
      root resorption, is available in the current literature. No accepted protocol or
      uniform guidelines for treatment in these cases exist, and many clinicians prefer
      avoiding replantation of an avulsed tooth that seems to have an uncertain
      longterm prognosis, or performing decoronation when infra-occlusion developed. As
      a result, young patients lose the benefits associated with replantation and
      decoronation procedures. The option of re-implantation of the avulsed teeth
      should be considered irrespective of the negative long-term prognosis. Following
      ankylosis development, the goal of submerging the tooth root (decoronation) is to
      maintain the horizontal dimension of the alveolar ridge and also to gain vertical
      dimension, allowing implant placement in the future.

PMID- 28761941
TI  - Effects of Different Concentrations and Excipients of Titanium Tetrafluoride on
      Dentin Erosion Prevention.
AB  - PURPOSE: To evaluate the preventive effect of titanium fluoride (TiF4) gel and
      solution, in different concentrations, on dentin erosion. MATERIALS AND METHODS:
      Of 140 root dentin slabs (3 x 3 x 1 mm) cut from 70 freshly extracted human third
      molars, 70 with intermediate Knoop microhardness and lowest surface curvature
      were selected and randomly divided into 7 groups (n = 10): G1: negative control
      (no treatment); G2: positive control (AmF/NaF/SnCl2 solution); G3: placebo gel
      (no fluoride); G4: 1% TiF4 solution; G5: 1% TiF4 gel; G6: 4% TiF4 solution; G7:
      4% TiF4 gel. Samples were subjected to 10 days of erosive cycling, consisting of
      alternating exposures to citric acid (0.05 M, pH 2.3, 2 min, 6x/day) and
      remineralizing solution (pH 7.0, 90 min, between acid exposures). Each cycle
      consisted of a total of 6 immersions in acid per day. After 5 and 10 days of pH
      cycling, surface loss was assessed by optical profilometry (um). RESULTS: One-way
      ANOVA and Tukey's test (p < 0.05) showed that after 5 days, G7 revealed a
      significant reduction in surface loss compared to the other groups, while G4, G5
      and G6 did not differ significantly from G1. After 10 days of erosive challenges,
      G7 did not differ significantly from G2 and there was no difference between G4,
      G5, G6 and G1. G3 showed the highest surface loss compared to all groups, except
      G1 and G5. CONCLUSION: The treatments tested were not able to prevent dentinal
      erosion, but the application of 4% TiF4 gel did reduce surface loss of dentin.

PMID- 28761942
TI  - Necrotising Ulcerative Gingivitis: A Literature Review.
AB  - PURPOSE: The literature surrounding necrotising ulcerative gingivitis (NUG) is
      extensive, yet the rare nature of this disease means that there is a lack of good
      quality research available. This paper aims to scrutinise the literature and
      provide an up-to-date summary of the available information. MATERIALS AND
      METHODS: A literature search was performed electronically using the Cochrane
      Library, Ovid Medline, Embase, PubMed Clinical Queries and Google Scholar.
      Keyword searches were carried out, utilising MeSH terms and free text. English
      language articles primarily were included, with key foreign language (French and
      German) articles included where possible from the 1900s to the present day.
      RESULTS: Necrotising ulcerative gingivitis is a rare disease (prevalence <1%),
      with an acute, painful and destructive presentation. It is an opportunistic
      bacterial infection which is predominantly associated with spirochetes. Treatment
      of NUG must be provided on a case-by-case basis, tailored to what the individual
      can tolerate and the extent of the infection. CONCLUSION: Although there is low
      prevalence of NUG, its importance should not be underestimated as one of the most
      severe responses to the oral biofilm. Risk factors must be investigated and
      addressed. Treatment should consist of gentle superficial debridement, oral
      hygiene instruction and prescription of mouthwash and antibiotics in severe
      cases.

PMID- 28761943
TI  - Vertical resonant tunneling transistors with molecular quantum dots for large
      scale integration.
AB  - Quantum molecular devices have a potential for the construction of new data
      processing architectures that cannot be achieved using current complementary
      metal-oxide-semiconductor (CMOS) technology. The relevant basic quantum transport
      properties have been examined by specific methods such as scanning probe and
      break-junction techniques. However, these methodologies are not compatible with
      current CMOS applications, and the development of practical molecular devices
      remains a persistent challenge. Here, we demonstrate a new vertical resonant
      tunneling transistor for large-scale integration. The transistor channel is
      comprised of a MOS structure with C60 molecules as quantum dots, and the
      structure behaves like a double tunnel junction. Notably, the transistors enabled
      the observation of stepwise drain currents, which originated from resonant
      tunneling via the discrete molecular orbitals. Applying side-gate voltages
      produced depletion layers in Si substrates, to achieve effective modulation of
      the drain currents and obvious peak shifts in the differential conductance
      curves. Our device configuration thus provides a promising means of integrating
      molecular functions into future CMOS applications.

PMID- 28761944
TI  - Topochemical polymerization of dumbbell-shaped diacetylene monomers: relationship
      between chemical structure, molecular packing structure, and gelation property.
AB  - Herein, we have synthesized novel photopolymerizable dumbbell-shaped diacetylene
      liquid crystal (LC) monomers by locating a diacetylene dicarboxylic acid group at
      the center and chemically connecting swallow-tails, such as hydrophobic alkyl
      chains (abbreviated as AT3DI) and amphiphilic biphenyl mesogens (abbreviated as
      BP3DI), with bisamide groups. Major phase transitions of dumbbell-shaped
      diacetylene monomers were identified using differential scanning calorimetry
      (DSC), polarized optical microscopy (POM), and Fourier transform infrared
      spectroscopy (FT IR). Molecular packing structures were studied based on
      structure-sensitive wide-angle X-ray diffraction (WAXD) and small-angle X-ray
      scattering (SAXS) analyses. Mainly, due to nanophase separations and strong
      intermolecular hydrogen bonding, AT3DI formed a low-ordered lamellar LC phase at
      room temperature. BP3DI self-assembled into highly-ordered crystal phases (K1 and
      K2) at lower temperatures below a low-ordered lamellar LC phase, in which BP3DI
      were intercalated with each other to compensate the mutual volume differences.
      From the photopolymerization of AT3DI and BP3DI, it was realized that the
      topochemical reactions of dumbbell-shaped diacetylene monomers were closely
      related to their chemical structures as well as molecular packing structures.

PMID- 28761945
TI  - Prescription Opioid Use, Misuse, and Use Disorders in U.S. Adults: 2015 National
      Survey on Drug Use and Health.
AB  - Background: Despite the continuing epidemic of opioid misuse, data on the
      prevalence of prescription opioid use, misuse, and use disorders are limited.
      Objective: To estimate the prevalence of prescription opioid use, misuse, and use
      disorders and motivations for misuse among U.S. adults. Design: Survey. Setting:
      The 2015 National Survey on Drug Use and Health (NSDUH). Participants: 72 600
      eligible civilian, noninstitutionalized adults were selected for NSDUH, and 51
      200 completed the survey interview. Measurements: Prescription opioid use,
      misuse, and use disorders. Results: Weighted NSDUH estimates suggested that, in
      2015, 91.8 million (37.8%) U.S. civilian, noninstitutionalized adults used
      prescription opioids; 11.5 million (4.7%) misused them; and 1.9 million (0.8%)
      had a use disorder. Among adults with prescription opioid use, 12.5% reported
      misuse; of these, 16.7% reported a prescription opioid use disorder. The most
      commonly reported motivation for misuse was to relieve physical pain (63.4%).
      Misuse and use disorders were most commonly reported in adults who were
      uninsured, were unemployed, had low income, or had behavioral health problems.
      Among adults with misuse, 59.9% reported using opioids without a prescription,
      and 40.8% obtained prescription opioids for free from friends or relatives for
      their most recent episode of misuse. Limitation: Cross-sectional, self-reported
      data. Conclusion: More than one third of U.S. civilian, noninstitutionalized
      adults reported prescription opioid use in 2015, with substantial numbers
      reporting misuse and use disorders. Relief from physical pain was the most
      commonly reported motivation for misuse. Economic disadvantage and behavioral
      health problems may be associated with prescription opioid misuse. The results
      suggest a need to improve access to evidence-based pain management and to
      decrease excessive prescribing that may leave unused opioids available for
      potential misuse. Primary Funding Source: U.S. Department of Health and Human
      Services.

PMID- 28761946
TI  - Treatment of Latent Tuberculosis Infection: An Updated Network Meta-analysis.
AB  - Background: Treatment of latent tuberculosis infection (LTBI) is an important
      component of tuberculosis (TB) control, and this study updates a previous network
      meta-analysis of the best LTBI treatment options to inform public health action
      and programmatic management of LTBI. Purpose: To evaluate the comparative
      efficacy and harms of LTBI treatment regimens aimed at preventing active TB among
      adults and children. Data Sources: PubMed, Embase, and Web of Science from
      indexing to 8 May 2017; clinical trial registries; and conference abstracts. No
      language restrictions were applied. Study Selection: Randomized controlled trials
      that evaluated human LTBI treatments and recorded at least 1 of 2 prespecified
      end points (hepatotoxicity and prevention of active TB). Data Extraction: 2
      investigators independently extracted data from eligible studies and assessed
      study quality according to a standard protocol. Data Synthesis: The network meta
      analysis of 8 new and 53 previously included studies showed that isoniazid
      regimens of 6 months (odds ratio [OR], 0.65 [95% credible interval {CrI}, 0.50 to
      0.83]) or 12 to 72 months (OR, 0.50 [CrI, 0.41 to 0.62]), rifampicin-only
      regimens (OR, 0.41 [CrI, 0.19 to 0.85]), rifampicin-isoniazid regimens of 3 to 4
      months (OR, 0.53 [CrI, 0.36 to 0.78]), rifampicin-isoniazid-pyrazinamide regimens
      (OR, 0.35 [CrI, 0.19 to 0.61]), and rifampicin-pyrazinamide regimens (OR, 0.53
      [CrI, 0.33 to 0.84]) were efficacious compared with placebo. Evidence existed for
      efficacy of weekly rifapentine-isoniazid regimens compared with no treatment (OR,
      0.36 [CrI, 0.18 to 0.73]). No conclusive evidence showed that HIV status altered
      treatment efficacy. Limitation: Evidence was sparse for many comparisons and
      hepatotoxicity outcomes, and risk of bias was high or unknown for many studies.
      Conclusion: Evidence exists for the efficacy and safety of 6-month isoniazid
      monotherapy, rifampicin monotherapy, and combination therapies with 3 to 4 months
      of isoniazid and rifampicin. Primary Funding Source: U.K. National Institute for
      Health Research. (PROSPERO: CRD42016037871).

PMID- 28761947
TI  - Prescription Opioid Use, Misuse, and Use Disorders in U.S. Adults.

PMID- 28761948
TI  - Prescription Opioid Use Among U.S. Adults: Our Brave New World.

PMID- 28761949
TI  - Immune Checkpoint Inhibitor Therapy in a Liver Transplant Recipient With
      Melanoma.

PMID- 28761950
TI  - Web Exclusives. Annals Graphic Medicine - American Doctors.

PMID- 28761951
TI  - The Scientific Basis of Guideline Recommendations on Sugar Intake.

PMID- 28761952
TI  - The Scientific Basis of Guideline Recommendations on Sugar Intake.

PMID- 28761953
TI  - The Scientific Basis of Guideline Recommendations on Sugar Intake.

PMID- 28761954
TI  - Guidelines to Limit Added Sugar Intake.

PMID- 28761955
TI  - Guidelines to Limit Added Sugar Intake.

PMID- 28761956
TI  - Should This Patient Receive an Antidepressant?: Grand Rounds Discussion From Beth
      Israel Deaconess Medical Center.
AB  - Depression is a major public health problem and a common cause of disability. To
      help physicians choose among available treatment options, the American College of
      Physicians recently issued a guideline titled "Nonpharmacologic Versus
      Pharmacologic Treatment of Adult Patients with Major Depressive Disorder." The
      evidence review done for the guideline found no statistically significant
      difference in the efficacy of second-generation antidepressants (SGAs) versus
      most other treatments for this disorder. However, rates of adverse events and
      discontinuation were generally higher in patients treated with SGAs. This Beyond
      the Guidelines reviews the guideline and includes a discussion between 2 experts
      on how they would apply it to a 64-year-old man with depression who is reluctant
      to begin medication. They review the data on which the guideline is based,
      discuss the limitations of applying the data to real-world settings, review how
      they would incorporate patient preferences when making treatment decisions, and
      outline options for patients in whom first-line therapy has failed.

PMID- 28761957
TI  - Crutches.

PMID- 28761958
TI  - Osteoporosis.
AB  - Osteoporosis is a common systemic skeletal disorder resulting in bone fragility
      and increased fracture risk. However, management of osteoporosis and fracture
      prevention strategies are often not addressed by primary care clinicians, even in
      older patients with recent fractures. Evidence-based screening strategies will
      improve identification of patients who are most likely to benefit from drug
      treatment to prevent fracture. In addition, careful consideration of when
      pharmacotherapy should be started and choice of medication and duration of
      treatment will maximize the benefits of fracture prevention while minimizing
      potential harms of long-term drug exposure.

PMID- 28761960
TI  - Seven Non-melanoma Features to Rule Out Facial Melanoma.
AB  - Facial melanoma is difficult to diagnose and dermatoscopic features are often
      subtle. Dermatoscopic non-melanoma patterns may have a comparable diagnostic
      value. In this pilot study, facial lesions were collected retrospectively,
      resulting in a case set of 339 melanomas and 308 non-melanomas. Lesions were
      evaluated for the prevalence (> 50% of lesional surface) of 7 dermatoscopic non
      melanoma features: scales, white follicles, erythema/reticular vessels, reticular
      and/or curved lines/fingerprints, structureless brown colour, sharp demarcation,
      and classic criteria of seborrhoeic keratosis. Melanomas had a lower number of
      non-melanoma patterns (p< 0.001). Scoring a lesion suspicious when no prevalent
      non-melanoma pattern is found resulted in a sensitivity of 88.5% and a
      specificity of 66.9% for the diagnosis of melanoma. Specificity was higher for
      solar lentigo (78.8%) and seborrhoeic keratosis (74.3%) and lower for actinic
      keratosis (61.4%) and lichenoid keratosis (25.6%). Evaluation of prevalent non
      melanoma patterns can provide slightly lower sensitivity and higher specificity
      in detecting facial melanoma compared with already known malignant features.

PMID- 28761961
TI  - Lethal Melanomas: A Population-based Registry Study in Western Sweden from 1990
      to 2014.
AB  - The incidence rates of thin melanomas (<=1 mm Breslow thickness) have increased
      in many fair-skinned populations, prompting a need to better identify patients
      with thin melanomas who will eventually die from the disease. This study aimed to
      describe the clinicopathological characteristics of lethal melanomas in Western
      Sweden, with a focus on thin lesions. Population-based data on invasive melanomas
      diagnosed during the years 1990 to 2014 were extracted from the Swedish Melanoma
      Registry, and linked to the Swedish Cause of Death Registry. The age-standardized
      incidence (US population 2000) of thin melanomas increased from 9.1*10-5 (95%
      confidence interval (95% CI) 8.5-9.8) to 21.3*10-5 (95% CI 20.4-22.1) during the
      study period. Thin melanomas comprised 55.2% of the total and contributed to
      13.5% of all melanoma deaths. Non-ulcerated melanomas 0.76-1 mm and ulcerated
      melanomas 0.26-1.0 mm showed a poorer survival compared with other thin
      melanomas.

PMID- 28761962
TI  - Coincident Metastatic Melanoma and Merkel Cell Carcinoma with Complete Remission
      on Treatment with Pembrolizumab.

PMID- 28761963
TI  - Photodynamic Therapy: Influence of Clinical and Procedure Variables on Treatment
      Response in Basal Cell Carcinoma and Bowen Disease.

PMID- 28761964
TI  - Hyperhidrosis Substantially Reduces Quality of Life in Children: A Retrospective
      Study Describing Symptoms, Consequences and Treatment with Botulinum Toxin.
AB  - Studies on children with hyperhidrosis are sparse. This retrospective study
      presents clinical data and quality of life, along with treatment effect and
      safety of botulinum toxin (BTX). Case reports from 366 children were included to
      capture the medical history of hyperhidrosis. The total median score of the
      Dermatology Life Quality Index before treatment was 11 for children aged 16-17
      years and 12 for children younger than 16 years. The children described physical,
      psychosocial and consequence-related symptoms. More than 70% had multifocal
      hyperhidrosis. BTX-A and/or BTX-B were given to 323 children, 193 of whom
      received repeated treatments. The highest score in a 5-grade scale concerning
      treatment effect was reported by 176/193 children, i.e. their "sweating
      disappeared completely". No severe adverse events occurred. Focal and multifocal
      hyperhidrosis in children reduces quality of life considerably. Treatment with
      BTX-A and/or BTX-B has been performed with success.

PMID- 28761965
TI  - [MTL30 as surrogate parameter for quality of surgically treated diseases :
      Establishment based on the StuDoQ register of the German Society for General and
      Visceral Surgery].
AB  - From a sociopolitical aspect there is increasing interest in the quality of
      healthcare. In this context valid, reproducible, comparable and risk-adjustable
      markers that are easily identified have become crucial for consistent
      documentation of quality. We recommend MTL30 (mortality, transfer, length of
      stay) as one of these markers to consistently measure the quality of large
      visceral surgical interventions. The MTL30 subsumes a number of known markers
      that may help to predict postoperative complications. The MTL30 is considered to
      be fulfilled when a patient on the 30th day following surgery, a) has died b) is
      still in the hospital or c) has been transferred to another acute care hospital.
      The evaluation of the StuDoQ register of the German Society for General and
      Visceral Surgery (DGAV) shows that MTL30 occurs significantly more often than any
      of the individual parameters. The correlation between MTL30 and other patient
      specific risk factors, e.g. American Society of Anesthesiologists classification
      (ASA), age, etc. enables a risk adjustment.

PMID- 28761966
TI  - [CAVE - A checklist system for preoperative risk evaluation : Guideline-conform
      cardiopulmonary diagnostics before general and visceral surgical interventions].
AB  - BACKGROUND: Preoperative evaluation of patient risk is an essential component of
      patient preparation before surgery. Guidelines provide evidence-based algorithms
      for preoperative assessment of cardiac risk; however, even experienced physicians
      correctly apply evidence-based algorithms in only 50% of all cases or less.
      OBJECTIVE: A checklist system for guideline-based cardiopulmonary risk evaluation
      in adult patients undergoing abdominal or visceral surgery (CAVE checklists) was
      created to assist in preoperative cardiopulmonary risk assessment and increase
      correct application of evidence-based algorithms before elective visceral
      surgery. MATERIAL UND METHODS: International guidelines were transformed into a
      checklist system. These checklists were than evaluated in a department of general
      and visceral surgery. The main goal was to determine whether preoperative
      examinations, such as electrocardiograph (ECG), chest-x-ray, spirometry and
      advanced assessment by a cardiologist, are performed according to evidence-based
      guidelines. The frequency of recommended as well as unnecessary and missed
      examinations was assessed. RESULTS: In this study 541 patients with a median age
      of 64.5 years (interquartile range: 52-73 years) were examined using the
      checklist system. Of the patients 90.4% underwent ECG and 98.5% chest-X-ray as
      recommended in the guidelines. Spirometry was not recommended in any patient and
      not performed in any case. Advanced assessment by a cardiologist was performed in
      45.5% of cases as recommended in the guidelines. When guidelines did not
      recommend ECG, x-ray, spirometry or advanced cardiac assessment, 69.4%, 99.6%,
      99.3% and 99.8% of patients, respectively, actually did not receive these
      examinations. Only 2.8% of all patients did not receive an examination that was
      recommended by the guidelines: 1.5% ECG, 0.2% x-ray and 1.1% advanced
      cardiological assessment. None of these patients suffered from postoperative
      cardiopulmonary complications. CONCLUSION: These simple checklists are easy to
      use and provide a higher degree of evidence-based preoperative cardiopulmonary
      risk evaluation than previously reported in the literature. Adaptation of the
      checklists to changing guidelines is easy to perform. Whether the application of
      these checklists will result in a reduction of morbidity and costs have to be
      determined in further clinical trials.

PMID- 28761967
TI  - Survival data for postoperative adjuvant chemotherapy comprising cisplatin plus
      vinorelbine after complete resection of non-small cell lung cancer.
AB  - PURPOSE: Despite the efficacy of postoperative adjuvant cisplatin (CDDP)-based
      chemotherapy for patients who have undergone surgical resection of non-small cell
      lung cancer (NSCLC), few reports have presented survival data for Asian patients
      treated with adjuvant chemotherapy involving a combination of CDDP and
      vinorelbine (VNR). This study was performed to evaluate the survival of patients
      with NSCLC who received postoperative adjuvant chemotherapy comprising CDDP +
      VNR. METHODS: We retrospectively evaluated patients with NSCLC who received
      adjuvant chemotherapy comprising CDDP + VNR at the Shizuoka Cancer Center between
      February 2006 and October 2011. RESULTS: One hundred patients who underwent
      surgical resection of NSCLC were included in this study. The patients'
      characteristics were as follows: median age 63 years (range 36-74 years), female
      34%, never-smokers 20%, and non-squamous NSCLC 73%. Pathological stages IIA, IIB,
      and IIIA were observed in 31, 22, and 47% of patients, respectively. The 5- and 2
      year overall survival rates were 73 and 93%, respectively. The 5- and 2-year
      relapse-free survival rates were 53 and 62%, respectively. Univariate analysis of
      prognostic factors showed that patient characteristics (sex, histology, and
      pathological stage) and CDDP dose intensity were not significantly associated
      with survival. In 48 patients who developed NSCLC recurrence, the 5-year survival
      rate after recurrence was 29%, and the median survival time after recurrence was
      37 months. CONCLUSIONS: Our results suggest that the prognosis after surgical
      resection of NSCLC and adjuvant chemotherapy comprising CDDP + VNR might be
      improving compared with previous survival data of adjuvant chemotherapy for
      NSCLC.

PMID- 28761969
TI  - Editorial: "Focus on disaster and military surgery".

PMID- 28761968
TI  - A retrospective study of amrubicin monotherapy for the treatment of relapsed
      small cell lung cancer in elderly patients.
AB  - PURPOSE: Amrubicin is one of the most active chemotherapeutic drugs for small
      cell lung cancer (SCLC). Previous studies reported its effectiveness and severe
      hematological toxicity. However, the efficacy of amrubicin monotherapy in elderly
      patients with SCLC has not been described. The objective of this study was to
      investigate the feasibility of amrubicin monotherapy in elderly patients and its
      efficacy for relapsed SCLC. METHODS: A retrospective cohort study design was
      used. We retrospectively evaluated the clinical effects and adverse events of
      amrubicin treatment in elderly (>=70 years) SCLC patients with relapsed SCLC.
      RESULTS: Between November 2003 and September 2015, 86 patients (aged >=70 years)
      received amrubicin monotherapy for relapsed SCLC at four institutions. There were
      42 cases of sensitive relapse (S) and 44 of refractory relapse (R). S cases with
      median age of 75 years (range 70-85 years) and R cases with median age of 74
      years (range 70-84 years) were included in our analysis. The median number of
      treatment cycles was three (range 1-9), and the response rate was 33.7% (40.5% in
      the S and 27.2% in the R cases). Median progression-free survival time was 4.0
      months in the S and 2.7 months in the R patients (p = 0.013). Median survival
      time from the start of amrubicin therapy was 7.6 months in the S and 5.5 months
      in the R cases (p = 0.26). The frequencies of grade >=3 hematological toxicities
      were as follows: leukopenia, 60.4%; neutropenia, 74.4%; anemia, 11.6%;
      thrombocytopenia, 16.2%; and febrile neutropenia, 17.4%. Treatment-related death
      was observed in one patient. CONCLUSION: Although hematological toxicities,
      particularly neutropenia, were severe, amrubicin showed favorable efficacy, not
      only in the S but also in the R cases, as shown in previous studies. Amrubicin
      could be a preferable standard treatment in elderly patients with relapsed SCLC.
      These results warrant further evaluation of amrubicin in elderly patients with
      relapsed SCLC by a prospective trial.

PMID- 28761970
TI  - [Feeding, eating, and swallowing disorders in infants and children : An
      overview].
AB  - Swallowing is a dynamic process that requires more than 30 muscles in the
      recruitment/coordination of the lips, tongue, palate, pharynx, larynx and
      esophagus. The eating and swallowing procedure is learned in sensitive or
      critical periods: when a certain degree of maturation has been achieved, the
      appropriate stimulus permits a certain milestone of development to occur. The
      swallowing procedure occurs in three main stages oral, pharyngeal, and
      esophageal. Therefore, swallowing disorders may present in any, some, or all of
      these stages in addition to feeding problems. Adult dysphagia, or difficulty
      swallowing, has long been reported in the literature. Infants and children also
      experience feeding disorders and swallowing problems, either because of
      developmental disorders, syndromes, behavioral or neurological conditions,
      respiratory problems, and/or gastroesophageal reflux, eosinophilic esophagitis or
      anatomical deficits. Feeding problems or dysphagia are seen in up to 25% of all
      children; approximately 40% of prematurely born infants have swallowing
      disorders, up to 64-78% with developmental disorders and up to 99% with cerebral
      palsy. Diagnostic options include health status, broad social environment, parent
      child interactions, and parental concerns. Evaluation of dysphagia and feeding
      disorders involves a multifactorial approach. Imaging studies may include
      videofluoroscopy and/or fiberoptic evaluation of swallowing (FEES). Successful
      oral feeding must be measured in quality of meal time experiences with best
      possible oral sensorimotor skills and safe swallowing while not jeopardizing a
      child's functional health status or the parent-child relationship. An
      interdisciplinary team approach enables coordinated global assessment and therapy
      planning.

PMID- 28761971
TI  - [Tufted angiomas of the head and neck. German version].
AB  - BACKGROUND: Tufted angiomas (TAs) are uncommon benign vascular tumors mostly
      located cutaneously or subcutaneously in the skin of the neck and upper trunk,
      which appear during childhood and grow slowly. TAs are a variant of lobular
      capillary hemangiomas. This is the first study to provide an overview of the
      current literature in combination with the authors' own clinical experience on
      this rare entity in the head and neck area with non-dermatological localization.
      METHODS: A selective Medline and Google Scholar database search was performed.
      Additionally, we conducted an ICD-10-based database search on hemangiomas (D18.0)
      in the Charite SAP patient records. RESULTS: We identified 13 reports in the
      literature consisting of 16 cases of TA of the head and neck. Males were
      predominantly affected by TAs (70.6%). The mean age of the patients at the time
      of surgery was 31.5 years; the mean maximum diameter of the tumors was 16.3 mm.
      Additionally, we report on one case of TA in our Department of Head and Neck
      Surgery. A male patient presented with swelling and redness of the left upper
      eyelid. Radiological examination with computed tomography showed a suprabulbar
      tumor with a diameter of 13 mm. The tumor was surgically removed via a
      transcutaneous blepharoplasty approach with the patient under general anesthesia.
      DISCUSSION: There is only one other case report on the surgical excision of an
      intra- orbital TA described to date. Here, we present an epidemiological
      overview, therapeutic considerations, and differential diagnoses.

PMID- 28761972
TI  - Evaluation of a New Fully Automated Assay for Plasma Intact FGF23.
AB  - Several FGF23 immunoassays are available. However, they are reserved for research
      purposes as none have been approved for clinical use. We evaluated the
      performances of a new automated assay for intact FGF23 on the DiaSorin Liaison
      platform which is approved for clinical use. We established reference values in
      908 healthy French subjects aged 18-89 years, and measured iFGF23 in patients
      with disorders of phosphate metabolism and in patients with chronic kidney
      disease (CKD). Intra-assay CV was 1.04-2.86% and inter-assay CV was 4.01-6.3%.
      The limit of quantification was <10 ng/L. Serum iFGF23 concentrations were
      considerably lower than EDTA values highlighting the importance of using
      exclusively EDTA plasma. Liaison iFGF23 values were approximately 25% higher than
      Immutopics values. In the 908 healthy subjects, distribution of the Liaison
      iFGF23 values was Gaussian with a mean +/- 2SD interval of 22.7-93.1 ng/L. Men
      had a slightly higher level than women (60.3 +/- 17.6 and 55.2 +/- 17.2 ng/L,
      respectively). Plasma iFGF23 concentration in 11 patients with tumour-induced
      osteomalacia, 8 patients with X-linked hypophosphatemic rickets, 43 stage 3a, 43
      stage 3b, 43 stage 4, 44 stage 5 CKD patients, and 44 dialysis patients were
      217.2 +/- 144.0, 150.9 +/- 28.6, 98.5 +/- 42.0, 130.8 +/- 88.6, 130.8 +/- 88.6,
      331.7 +/- 468.2, 788.8 +/- 1306.6 and 6103.9 +/- 11,178.8 ng/L, respectively.
      This new iFGF23 assay available on a platform that already allows the measurement
      of other important parameters of the mineral metabolism is a real improvement for
      the laboratories and clinicians/researchers involved in this field.

PMID- 28761973
TI  - Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone
      Mineral Density and Breast Cancer.
AB  - Epidemiological and clinical evidences have shown that bone mineral density (BMD)
      has a close relationship with breast cancer (BC). They might potentially have a
      shared genetic basis. By incorporating information about these pleiotropic
      effects, we may be able to explore more of the traits' total heritability. We
      applied a recently developed conditional false discovery rate (cFDR) method to
      the summary statistics from two independent GWASs to identify the potential
      pleiotropic genetic variants for BMD and BC. By jointly analyzing two large
      independent GWASs of BMD and BC, we found strong pleiotropic enrichment between
      them and identified 102 single-nucleotide polymorphisms (SNPs) in BMD and 192
      SNPs in BC with cFDR < 0.05, including 230 SNPs that might have been overlooked
      by the standard GWAS analysis. cFDR-significant genes were enriched in GO terms
      and KEGG pathways which were crucial to bone metabolism and/or BC pathology (adjP
      < 0.05). Some cFDR-significant genes were partially validated in the gene
      expressional validation assay. Strong interactions were found between proteins
      produced by cFDR-significant genes in the context of biological mechanism of bone
      metabolism and/or BC etiology. Totally, we identified 7 pleiotropic SNPs that
      were associated with both BMD and BC (conjunction cFDR < 0.05); CCDC170, ESR1,
      RANKL, CPED1, and MEOX1 might play important roles in the pleiotropy of BMD and
      BC. Our study highlighted the significant pleiotropy between BMD and BC and shed
      novel insight into trait-specific as well as the potentially shared genetic
      architecture for both BMD and BC.

PMID- 28761974
TI  - Dicalcium Phosphate Anhydrous: An Appropriate Bioceramic in Regeneration of
      Critical-Sized Radial Bone Defects in Rats.
AB  - The present study aimed to evaluate and compare the effectiveness of composites
      of calcium phosphates including beta-tri calcium phosphate (beta-TCP), dicalcium
      phosphate anhydrous (DCPA, monetite), mono-calcium phosphate monohydrate (MCPM),
      and hydroxyapatite (HA) with the chitosan-gelatin-platelet gel (CGP) on the
      healing of experimentally induced critical size radial bone defects in rats after
      8 weeks of injury. Eighty bilateral bone defects were created in the radial bones
      of 40 adult male Sprague-Dawley rats. The defects were either left empty
      (untreated or defect group), or treated with autograft, CGP, CGP-DCP, CGP-TCP,
      CGP/beta-TCP/DCPA (CGP-TD), CGP-TD/MCPM (CGP-TDM), and CGP-TDM/HA (CGP-TDMH)
      scaffolds. The injured forelimbs were evaluated by radiography, gross morphology,
      three-dimensional computed tomography scanning, histopathology, histomorphometry,
      scanning electron microscopy, and biomechanical testing. The materials were
      analyzed using X-ray diffraction to verify the crystalline nature of their
      structures, and their crystallinity was revealed based on the diffraction peaks
      achieved from the XRD analysis. The best results were achieved by the CGP-DCP
      scaffold and the autograft. The CGP-TCP and CGP-TDMH scaffolds were not degraded,
      while the CGP-DCP, CGP-TDM, CGP-TD, and CGP scaffolds were biodegraded and
      enhanced bone formation compared with the CGP-TCP and CGP-TDMH groups (P < 0.05).
      Overall, the CGP-DCP treated defects showed significant improvement in bone
      formation and union, bone volume, maximum load, and stiffness compared to the CGP
      group (P < 0.05). It could be concluded that the CGP-DCP scaffold can be
      considered as a suitable substitute to autograft. In fact, this study
      demonstrated that DCPA or monetite has high healing potential due to its
      biocompatibility, biodegradability and biomechanical, osteoconductive and
      osteoinductive properties of this bioceramic.

PMID- 28761975
TI  - Interim FDG-PET in lymphoma, a questionable practice in hematology.

PMID- 28761976
TI  - Physiological proteins in resource-limited herbivores experiencing a population
      die-off.
AB  - Nutrient availability is predicted to interact with herbivore population
      densities. Competition for low quality food at high density may reduce summer
      food intake, and in turn winter survival. Conversely, low population density may
      favor physiological recovery through better access to better quality spring
      forage. Here, we take advantage of the long-term study of the Soay sheep
      population of St. Kilda (Scotland) to measure plasma protein markers and immunity
      in two consecutive summers with contrasting population densities. We show that,
      following a winter die-off resulting in a shift to low population density,
      albumin and total proteins increased, but only in adult sheep. The effect was not
      solely attributable to selective disappearance of malnourished sheep. Similarly,
      the concentration of antibodies was higher following the die-off, potentially
      indicating recovery of immune function. Overall, our results are consistent with
      the physiological recovery of surviving individuals after a harsh winter.

PMID- 28761977
TI  - Calcineurin inhibitors regulate fibroblast growth factor 23 (FGF23) synthesis.
AB  - Fibroblast growth factor 23 (FGF23) inhibits renal phosphate reabsorption and
      calcitriol formation, effects depending on Klotho as a co-receptor for FGF23. In
      addition, FGF23/Klotho strongly influences aging and the onset of age-associated
      diseases. The synthesis of FGF23 by bone cells is induced by store-operated Ca2+
      entry (SOCE) through Orai1 in UMR106 osteoblast-like cells. Ca2+ entry activates
      the phosphatase calcineurin in many cell types which dephosphorylates nuclear
      factor of activated T cells (NFAT) thereby stimulating its transcriptional
      activity. Here, we explored whether calcineurin-NFAT signaling impacts on FGF23
      production. Fgf23 transcripts were determined by qRT-PCR and FGF23 protein by
      ELISA. Calcineurin as well as NFAT expression were quantified by RT-PCR in UMR106
      cells. UMR106 cells expressed calcineurin subunits Ppp3r1, Ppp3ca, Ppp3cb, and
      Ppp3cc as well as NFATc1, NFATc3, and NFATc4. Calcineurin inhibitors ciclosporin
      A (CsA) and tacrolimus (FK-506) decreased Fgf23 gene expression and FGF23 protein
      production. Moreover, calcineurin-NFAT interaction inhibitor INCA-6 reduced the
      abundance of Fgf23 transcripts as well as FGF23 protein. Calcineurin-NFAT
      signaling is a potent regulator of FGF23 formation.

PMID- 28761978
TI  - Propolis alleviates concanavalin A-induced hepatitis by modulating cytokine
      secretion and inhibition of reactive oxygen species.
AB  - Viral hepatitis-induced oxidative stress accompanied by increased levels of
      transforming growth factor-beta (TGF-beta) and hepatic fibrosis are hallmarks of
      hepatitis C virus infection. The present study was designed to investigate the
      potential protective effect of propolis against liver injury induced by
      concanavalin A (Con A), a T-cell-dependent model that causes an immune-mediated
      hepatitis in a similar pattern to the one induced by viral infections. In the
      present study, rats were randomly divided into four groups. The first group
      (control) was administered the vehicle of Con A (i.v.) for 24 h. The second group
      received Con A (12 mg/kg body weight i.v.) for 24 h. The third group received
      propolis (300 mg/kg by oral gavage) 5 days before and concurrently with Con A for
      24 h. The last group received propolis alone. Following a single injection of Con
      A, histopathological changes as well as significant reduction in albumin level
      were observed. In addition, serum levels of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), and total bilirubin were significantly
      increased. These increases correlated with an increase in lipid peroxidation and
      downregulation of reduced glutathione (GSH) as well as superoxide dismutase (SOD)
      and catalase activities in liver tissue. Furthermore, these changes were
      associated with an increase in serum levels of the inflammatory cytokines tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) as well as the
      profibrotic cytokine TGF-beta. Moreover, TGF- beta activation was accompanied
      with an increase in Smad phosphorylation. Interestingly, concomitant
      administration of propolis along with Con A significantly attenuated all these
      negative effects and improved liver function indicating that propolis has the
      ability to protect rats from Con A-induced hepatitis.

PMID- 28761979
TI  - Probiotics and Probiotic Metabolic Product Improved Intestinal Function and
      Ameliorated LPS-Induced Injury in Rats.
AB  - In the present study, we sought to determine the effects of Bacillus subtilis
      (BAS) and Bacillus licheniformis (BAL) in rats after lipopolysaccharide (LPS)
      induced acute intestinal inflammation. We also determined whether the B. subtilis
      metabolic product (BASM) is as effective as the live-cell probiotic. 60 male SD
      rats were randomly assigned to five groups and administered a diet containing
      0.05% B. licheniformis (BAL group), 0.05% B. subtilis (BAS group), 0.5% B.
      subtilis metabolic product (BASM group), or a basic diet (PC group and NC group)
      for 40 days. On day 40, BAL, BAS, BASM, and NC groups were injected with 4 mg/kg
      body weight LPS. 4 h later, all rats were anesthetized and sacrificed. The
      results showed that the administration of B. licheniformis and B. subtilis
      improved intestinal function as evidenced by histology, increased enzyme
      activity, and mucosal thickness. They also increased the number of
      intraepithelial lymphocytes and decreased mucosal myeloperoxidase activity and
      plasma TNF-alpha. In addition, the cecal content of B. subtilis-treated rats had
      significantly increased microbial diversity, decreased numbers of Firmicutes, and
      increased numbers of Bacteroidetes as compared to rats fed basic diets. Similar
      to BAS group, the cecal content of B. licheniformis-treated rats decreased the
      number of Firmicutes. Administration of B. subtilis metabolic product had similar
      effects on intestinal function, inflammation response, and microbial diversity as
      B. subtilis but these effects were attenuated. In conclusion, administration of
      probiotic strains B. licheniformis or B. subtilis improved intestinal function,
      ameliorated the inflammation response, and modulated microflora after LPS-induced
      acute inflammation in rats. Non-living cells also exerted probiotic properties
      but live cells tended to function better.

PMID- 28761980
TI  - Effects of Disodium Fumarate on In Vitro Rumen Fermentation, The Production of
      Lipopolysaccharide and Biogenic Amines, and The Rumen Bacterial Community.
AB  - The effect of disodium fumarate (DF) on the ruminal fermentation profiles, the
      accumulation of lipopolysaccharide (LPS) and bioamines, and the composition of
      the ruminal bacterial community was investigated by in vitro rumen fermentation.
      The addition of DF increased the total gas production; the concentrations of
      propionate, valerate, total volatile fatty acids, and ammonia-nitrogen; and the
      rumen pH after a 24 h fermentation. By contrast, DF addition decreased the ratio
      of acetate to propionate and the concentrations of lactate, lipopolysaccharide,
      methylamine, tryptamine, putrescine, histamine, and tyramine (P < 0.05).
      Principal coordinates analysis and molecular variance analysis showed that DF
      altered the ruminal bacterial community (P < 0.05). At the phylum level, DF
      decreased the proportion of Proteobacteria, and increased the proportions of
      Spirochaetae and Elusimicrobia (P < 0.05). At the genus level, DF decreased the
      percentage of Ruminobacter, while increasing the percentage of Succinivibrio and
      Treponema (P < 0.05). Overall, the results indicate that DF modified rumen
      fermentation and mitigated the production of several toxic compounds. Thus, DF
      has great potential for preventing subacute rumen acidosis in dairy cows and for
      improving the health of ruminants.

PMID- 28761981
TI  - Comparison of infrared canopy temperature in a rubber plantation and tropical
      rain forest.
AB  - Canopy temperature is a result of the canopy energy balance and is driven by
      climate conditions, plant architecture, and plant-controlled transpiration. Here,
      we evaluated canopy temperature in a rubber plantation (RP) and tropical
      rainforest (TR) in Xishuangbanna, southwestern China. An infrared temperature
      sensor was installed at each site to measure canopy temperature. In the dry
      season, the maximum differences (Tc - Ta) between canopy temperature (Tc) and air
      temperature (Ta) in the RP and TR were 2.6 and 0.1 K, respectively. In the rainy
      season, the maximum (Tc - Ta) values in the RP and TR were 1.0 and -1.1 K,
      respectively. There were consistent differences between the two forests, with the
      RP having higher (Tc - Ta) than the TR throughout the entire year. Infrared
      measurements of Tc can be used to calculate canopy stomatal conductance in both
      forests. The difference in (Tc - Ta) at three gc levels with increasing direct
      radiation in the RP was larger than in the TR, indicating that change in (Tc -
      Ta) in the RP was relatively sensitive to the degree of stomatal closure.

PMID- 28761982
TI  - Occlusal, chewing, and tasting characteristics associated with orofacial
      dysfunctions in children with unilateral cleft lip and palate: a case-control
      study.
AB  - OBJECTIVE: The objective of this study is to assess the associations between
      orofacial dysfunctions with malocclusion, masticatory performance, and taste in
      children with and without unilateral cleft lip and palate (UCLP). MATERIAL AND
      METHODS: A patient-based, matched, case-control study was conducted involving 108
      8- to 10-year-old children divided in UCLP and control groups. Orofacial
      dysfunctions were evaluated using the Nordic Orofacial Test-Screening (NOT-S).
      Orthodontic treatment need was evaluated using the Goslon Yardstick Index (GYI)
      and the Index of Orthodontic Treatment Need (IOTN) of patients and controls,
      respectively. Masticatory performance was assessed using a chewable test material
      to determine median particle size (X 50) and distribution of particles in
      different sieves (b value). Taste perception was evaluated using four solutions
      (sweet, salty, bitter, or acid) in three different concentrations. RESULTS: More
      than half of the patients needed orthodontic surgery. UCLP group presented higher
      median particle size and needed more chewing cycles to comminute the artificial
      test into particles smaller than the median than those of controls. UCLP group
      had less perception of salty flavor than controls. There was a positive
      correlation between b value and NOT-S examination score for patients. In
      regression analysis, a significant interrelationship was observed between NOT-S
      examination score and b value. CONCLUSIONS: In the UCLP patients, masticatory
      performance was compromised probably as a result of facial asymmetry and speech
      disturbance; whereas, taste was less perceived only for salty flavor. CLINICAL
      RELEVANCE: These findings provide preliminary evidence that mastication and taste
      are altered in children with UCLP, so these factors must be followed up to ensure
      oral and general health in growing individuals.

PMID- 28761983
TI  - Effect of mechanical loading on the metabolic activity of cells in the
      temporomandibular joint: a systematic review.
AB  - OBJECTIVES: The purpose of this systematic review was to elucidate how different
      modalities and intensities of mechanical loading affect the metabolic activity of
      cells within the fibro-cartilage of the temporomandibular joint (TMJ). MATERIALS
      AND METHODS: A systematic review was conducted according to PRISMA guidelines
      using PubMed, Embase, and Web of Science databases. The articles were selected
      following a priori formulated inclusion criteria (viz., in vivo and in vitro
      studies, mechanical loading experiments on TMJ, and the response of the TMJ). A
      total of 254 records were identified. After removal of duplicates, 234 records
      were screened by assessing eligibility criteria for inclusion. Forty-nine
      articles were selected for full-text assessment. Of those, 23 were excluded
      because they presented high risk of bias or were reviews. Twenty-six experimental
      studies were included in this systematic review: 15 in vivo studies and 11 in
      vitro ones. CONCLUSION: The studies showed that dynamic mechanical loading is an
      important stimulus for mandibular growth and for the homeostasis of TMJ
      cartilage. When this loading is applied at a low intensity, it prevents breakdown
      of inflamed cartilage. Yet, frequent overloading at excessive levels induces
      accelerated cell death and an increased cartilage degradation. CLINICAL
      SIGNIFICANCE: Knowledge about the way temporomandibular joint (TMJ)
      fibrocartilage responds to different types and intensities of mechanical loading
      is important to improve existing treatment protocols of degenerative joint
      disease of the TMJ, and also to better understand the regenerative pathway of
      this particular type of cartilage.

PMID- 28761984
TI  - Embryonic and post-embryonic development inside wolf spiders' egg sac with
      special emphasis on the vitellus.
AB  - The development of Pardosa saltans wolf spiders inside an egg sac includes two
      periods: an embryonic period and a post-embryonic period after hatching. We
      investigated spiderlings' energy expenditure to assess energetic costs during the
      different embryonic and post-embryonic developmental stages during which they are
      confined within their egg sac. We focused on the following developmental stages:
      egg, embryonic stages 1 and 2, and two stages, separated by a moult, during post
      embryogenesis inside the egg sac: "juvenile instars 1 and 2" until emergence of 2
      instar juveniles from their egg sac. We present the first biochemical
      characterization of the vitellus of wolf spiders' eggs, embryos and juveniles.
      Lipovitellins (LV) are composed of four apolipoproteins of 116, 87, 70 and 42
      kDa, respectively, and LV represent 35-45% of total protein during development.
      The principal LV lipids are triglycerides, phospholipids, free fatty acids and
      sterols. Egg caloric content averaged 127 cal/g (proteins: 91 cal/g, lipids: 33
      cal/g, carbohydrates: 3 cal/g). During development from undivided egg to emerged
      "juvenile 2", 67% of proteins, 51% of carbohydrates and 49% of triglycerides
      stocks were depleted. At the end of the post-embryonic period, at emergence from
      egg sac, body energy stock of "juveniles 2" was 38% of the initial calorie stocks
      in the eggs.

PMID- 28761985
TI  - Synovial sarcoma showing loss of a green signal in SS18 fluorescence in situ
      hybridization: a clinicopathological and molecular study of 12 cases.
AB  - The phenomenon of losing a green signal in synovial sarcoma (SS) using the SS18
      break-apart probe by fluorescence in situ hybridization (FISH) has been poorly
      described. In this study, 12 SS with missing a green signal were identified. This
      series included 7 males and 5 females, aged 17 to 69 years (median, 38.5 years).
      The tumors involved the extremities (50%), mediastinum (16.7%), hypopharynx
      (8.3%), neck (8.3%), thyroid (8.3%), and retroperitoneum (8.3%). The tumors were
      classified as monophasic SS (58.3%) and poorly differentiated SS (41.7%). An
      anaplastic SS showing features of pleomorphic sarcoma was observed.
      Immunostaining for TLE1, BCL2, CD99, epithelial membrane antigen, cytokeratin
      (AE1/AE3), cytokeratin 7, S-100 protein, and CD34 was consistent with typical SS.
      In FISH, all the tumors showed the pattern of 1 to 3 fused signal(s) with 1 to 3
      red signal(s), without corresponding a green signal. The fusion transcripts
      included SS18-SSX1 (8/10, 80%) and SS18-SSX2 (2/10, 20%) fusions. Median and 5
      year overall survival were 19.1 months and 43.6%, respectively. In conclusion, we
      reported a series of SS losing a green signal in the SS18 FISH assay. We propose
      that this variant FISH pattern should be interpreted as a peculiar unbalanced
      rearrangement of the SS18 gene and subsequent SS18-SSX fusion test should be
      recommended. The cases in this study seem to show some unusual
      clinicopathological features, including unusual locations, higher proportions of
      poorly differentiated SS, and aggressive clinical course. However, whether this
      variant FISH pattern is associated with peculiar clinicopathologic features
      awaits larger series.

PMID- 28761986
TI  - Smoking cessation reduces the lectin-like low-density lipoprotein receptor index,
      an independent cardiovascular risk marker of vascular inflammation.
AB  - Vessel wall inflammation promotes the destabilization of atherosclerotic plaques.
      The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1)
      expressed by vascular cells and monocytes. LOX index is calculated by multiplying
      LOX-1 ligand containing apolipoprotein B level with the soluble LOX-1. A high LOX
      index reflects an increased risk for stroke and myocardial infarction. However,
      the change in LOX index after smoking cessation and the relationship between
      smoking-related variables and LOX index are unknown. Relation of the clinical
      parameters to the LOX index was examined on 180 subjects (135 males and 45
      females) at the first visit to our outpatient clinic for smoking cessation. The
      impact of smoking cessation on the LOX index was also determined in the 94
      subjects (62 males and 32 females) who successfully stopped smoking. Sex-adjusted
      regression analysis and multivariate analysis identified three independent
      determinants of the LOX index, namely, low-density lipoprotein-cholesterol (LDL
      C; beta = 0.311, p < 0.001), high-sensitivity C-reactive protein (beta = 0.358, p
      < 0.001), and expired carbon monoxide concentration reflecting smoking heaviness
      (beta = 0.264, p = 0.003). Body mass index (BMI) significantly increased 3 months
      after the onset of smoking cessation (p < 0.001). However, the LOX index
      significantly decreased (p < 0.001), regardless of the rate of increase in BMI
      post-cessation. The LOX index is closely associated with smoking heaviness as
      well as dyslipidemia and an inflammation marker. Smoking cessation may induce a
      decrease in this cardiovascular risk marker, independently of weight gain.

PMID- 28761987
TI  - Depression, anxiety, and mental health service experiences of women with a twin
      twin transfusion syndrome pregnancy.
AB  - Symptoms of emotional distress during and after pregnancy may be introduced or
      exacerbated by unexpected medical conditions in the mother or fetus. Twin-twin
      transfusion syndrome (TTTS), which accounts for 17% of fetal deaths in twins and
      entails substantial medical uncertainty, may represent a particularly challenging
      pregnancy experience. Yet, little is known about the impact of TTTS on women's
      emotional health. We retrospectively surveyed 350 women who experienced a TTTS
      pregnancy about their experiences at three time points (prior to, during, and
      after pregnancy) to examine symptoms of anxiety and depression, mental health
      diagnoses, thoughts of seeking mental healthcare, help received, and preferred
      mental health services. Women in this study experienced significantly elevated
      symptoms of depression and anxiety during and after pregnancy, regardless of
      their pregnancy outcome (double survivor, single survivor, or double loss). Women
      reported feeling devastated by their experience and indicated they would have
      accepted mental healthcare had it been offered and had barriers to care been
      addressed. Prospective studies of women experiencing TTTS pregnancies are needed
      to examine TTTS effects on maternal mental health and to determine how to best
      address emotional care needs.

PMID- 28761988
TI  - Neurological soft signs precede the onset of schizophrenia: a study of
      individuals with schizotypy, ultra-high-risk individuals, and first-onset
      schizophrenia.
AB  - Neurological soft signs (NSS) are one of the biomarkers for schizophrenia
      spectrum disorders. However, a few studies have examined the prevalence of NSS
      across the schizophrenia spectrum. The present study adopted a quasi-longitudinal
      study design and examined the prevalence of NSS and their associations with
      clinical and behavioural manifestations in participants in different stages of
      the illness. The abridged version of the Cambridge Neurological Inventory was
      administered to 39 patients with the first-episode schizophrenia, 39 individuals
      with ultra-high risk (UHR) for psychosis, 39 individuals with schizotypy, and 39
      healthy controls. Patients with the first-episode schizophrenia had a higher
      prevalence of NSS in motor coordination than healthy controls as well as
      individuals with UHR and schizotypy. Individuals with UHR exhibited a higher
      prevalence of sensory integration items than individuals with schizotypy and
      healthy controls. Discriminant analysis classified the membership of the
      individuals correctly across the spectrum with an accuracy of up to 60.9%. In
      particular, NSS could discriminate individuals with UHR from healthy controls at
      up to 85.9% accuracy. These findings suggest that NSS are robust biomarkers to
      detect and discriminate individuals in different stages of the schizophrenia
      spectrum from healthy controls.

PMID- 28761989
TI  - Comparing the dimensional structure and diagnostic algorithms between DSM-5 and
      ICD-11 PTSD in children and adolescents.
AB  - In contrast to the DSM-5, which expanded the posttraumatic stress disorder (PTSD)
      symptom profile to 20 symptoms, a workgroup of the upcoming ICD-11 suggested a
      reduced symptom profile with six symptoms for PTSD. Therefore, the objective of
      the study was to investigate the dimensional structure of DSM-5 and ICD-11 PTSD
      in a clinical sample of trauma-exposed children and adolescents and to compare
      the diagnostic rates of PTSD between diagnostic systems. The study sample
      consisted of 475 self-reports and 424 caregiver-reports on the child and
      adolescent trauma screen (CATS), which were collected at pediatric mental health
      clinics in the US, Norway and Germany. The factor structure of the PTSD construct
      as defined in the DSM-5 and in alternative models of both DSM-5 and ICD-11 was
      investigated using confirmatory factor analyses (CFA). To evaluate differences in
      PTSD prevalence, McNemar's tests for correlated proportions were used. CFA
      results demonstrated excellent model fit for the proposed ICD-11 model of PTSD.
      For the DSM-5 models we found the best fit for the hybrid model. Diagnostic rates
      were significantly lower according to ICD-11 (self-report: 23.4%; caregiver
      report: 16.5%) compared with the DSM-5 (self-report: 37.8%; caregiver-report:
      31.8%). Agreement was low between diagnostic systems. Study findings provide
      support for an alternative latent dimensionality of DSM-5 PTSD in children and
      adolescents. The conceptualization of ICD-11 PTSD shows an excellent fit.
      Inconsistent PTSD constructs and significantly diverging diagnostic rates between
      DSM-5 and the ICD-11 will result in major challenges for researchers and
      clinicians in the field of psychotraumatology.

PMID- 28761991
TI  - Biofeedback-Aided Relaxation Training Helps Emotional Disturbances in
      Undergraduate Students Before Examination.
AB  - The main aim of the present research was to determine the effectiveness of
      biofeedback-aided relaxation training (BFRT) for alleviating symptoms of
      depression, anxiety, and stress for undergraduate students as they prepared for
      their final examinations. In a randomized controlled trial design, 29 male and
      female students, with heightened levels of depression, anxiety and stress scores
      on the Depression, Anxiety, and Stress Scale, were chosen and randomly assigned
      to BFRT or a no-treatment control condition. Subjects assigned to BFRT received
      eight sessions of BFRT spaced over 4 weeks, during which they were trained to
      decrease electromyography (EMG) and respiration rate (RESP) and to increase skin
      temperature (TEMP). Data were extracted and analyzed by GLM statistical analysis.
      Students receiving BFRT revealed significant reductions in symptoms when compared
      to the untreated controls. Those receiving BFRT also showed significant changes
      for the three targeted psychophysiological modalities (EMG, RESP, and TEMP). It
      was concluded that BFRT can be useful for reducing symptoms of emotional
      disturbance in undergraduate students during a particularly stressful period and
      that this may, in turn, help promote overall psychological health.

PMID- 28761990
TI  - Roburic Acid Suppresses NO and IL-6 Production via Targeting NF-kappaB and MAPK
      Pathway in RAW264.7 Cells.
AB  - In the present study, we investigated the anti-inflammatory effect of roburic
      acid on production of nitric oxide (NO) and interlukin-6 (IL-6) in
      lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. We found that
      roburic acid reduced production of NO and IL-6, and the expression of inducible
      nitric oxide synthases (iNOS). Meanwhile, phosphorylation of inhibitor of
      kappaBalpha (IkappaBalpha) and IkappaB kinase alpha/beta (IKKalpha/beta), as well
      as translocation of nuclear factor-kappaB (NF-kappaB) to the nucleus, was
      suppressed by roburic acid treatment. In addition, phosphorylation of mitogen
      activated protein kinase (MAPKs) including p38 and c-Jun-NH2-terminal kinase
      (JNK) was inhibited. Roburic acid exhibited inhibitory activities on production
      of NO and IL-6 via blocking IKK/IkappaB/NF-kappaB and MAPKs pathway, suggesting
      the potential application as a drug candidate for therapy of inflammatory
      diseases.

PMID- 28761992
TI  - Novel technique for airless connection of artificial heart to vascular conduits.
AB  - Successful implantation of a total artificial heart relies on multiple
      standardized procedures, primarily the resection of the native heart, and
      exacting preparation of the atrial and vascular conduits for pump implant and
      activation. Achieving secure pump connections to inflow/outflow conduits is
      critical to a successful outcome. During the connection process, however, air may
      be introduced into the circulation, traveling to the brain and multiple organs.
      Such air emboli block blood flow to these areas and are detrimental to long-term
      survival. A correctly managed pump-to-conduit connection prevents air from
      collecting in the pump and conduits. To further optimize pump-connection
      techniques, we have developed a novel connecting sleeve that enables airless
      connection of the Cleveland Clinic continuous-flow total artificial heart (CFTAH)
      to the conduits. In this brief report, we describe the connecting sleeve design
      and our initial results from two acute in vivo implantations using a scaled-down
      version of the CFTAH.

PMID- 28761993
TI  - Coumarin impairs redox homeostasis in wheat aleurone layers.
AB  - Many plant families produce coumarin (COU) and its derivatives as secondary
      metabolites via the phenylpropanoid biosynthetic pathway. This ubiquitous group
      of phytochemicals was shown to have diverse physiological effects on cellular,
      tissue, and organ levels. So far, research dealing with the hormonal like
      behavior of COU and its interaction with the activity and/or transport of
      phytohormones is very limited. In the current study, the impact of COU on redox
      homeostasis in aleurone layers of wheat grains was investigated. Aleurone layers
      were incubated in either 1000 MUM COU or 5 MUM gibberellic acid (GA3) alone or in
      combination with 5 MUM abscisic acid (ABA). Results revealed that both COU and
      GA3 treatments induced the production of alpha-amylase but inhibited the
      activities of superoxide dismutase, catalase and ascorbate peroxidase. The
      downregulation of antioxidant enzymes that is provoked by COU and GA3 was
      accompanied by significant accumulation of both H2O2 and malondialdehyde. In
      contrast with the effect of ABA, both COU and GA3 treatments resulted in a
      significant reduction in cell viability as revealed by trypan blue staining.
      These results suggest that COU could disrupt the redox balance in aleurone layers
      through downregulation of the enzymatic antioxidant system. Therefore, the
      current study provides evidence for the gibberellin like activity of COU.

PMID- 28761994
TI  - The effect of bariatric surgery on the retrobulbar flow hemodynamic parameters in
      patients with obesity: color Doppler evaluation.
AB  - PURPOSE: To evaluate the effect of weight loss on the retrobulbar hemodynamics in
      patients who had undergone bariatric surgery for obesity using color Doppler
      ultrasound (CDU) and to evaluate correlations with intraocular pressure (IOP)
      changes measured using Goldman applanation tonometry. METHODS: Thirty-two
      patients were included in this prospective study. Body mass index (BMI), IOP
      measurements, and retrobulbar CDU examination were performed on all individuals 6
      months before and after bariatric surgery. RESULTS: The preoperative mean BMI
      value was 48.8 +/- 2.27 kg/m2, and mean IOP value was 18.2 +/- 2.06 mmHg. At 6
      months postoperatively, mean BMI and IOP were 36.28 +/- 5.41 kg/m2 and 16.1 +/-
      1.81 mmHg which was statistically significantly lower than the preoperative
      measurements (p < 0.001). In the comparison of pre- and postoperative orbital CDU
      value, the preoperative OA PSV (30.16 +/- 5.31 cm/s) and OA EDV (10.93 +/- 3.04)
      values were significantly lower than the postoperative OA PSV (36.21 +/- 5.56)
      and OA EDV (12.84 +/- 3.38) values (p < 0.001 and p < 0.05, respectively). A
      significant correlation was determined between BMI and IOP (r = -0.443; p <
      0.05). CONCLUSIONS: Decrease in body weight resulting from bariatric surgery
      performed on morbid obese patients causes alterations in both IOP and retrobulbar
      hemodynamics. Morbidly obese patients who undergo bariatric surgery have
      statistically significantly lower IOP values and increase in OA Doppler
      parameters (PSV, EDV) than in the preoperative period, which reflects a better
      retrobulbar and ocular blood flow.

PMID- 28761995
TI  - Intermediate term thrombotic risk in contemporary total cavo-pulmonary connection
      for single ventricle circulations.
AB  - Despite the common occurrence of thrombosis in Fontan circulations, the mid-term
      thrombotic risk beyond the first two postoperative years is poorly defined
      especially in total cavo pulmonary Fontan. This study examines the thrombotic
      incidence and risk beyond the first 2 years after contemporary Fontan surgery.
      Using a retrospective cohort study design, 89 Fontan patients, 50 male, were
      included and evaluated with a median of 8.3 years (IQR 6.8-11.4) follow-up.
      Hospital records were reviewed for known risk factors of thrombosis, thrombotic
      events, antiplatelet and anticoagulation management, and basic characteristics.
      Forty seven patients (52%) had a dominant left ventricle, and 28 (32%) had
      hypoplastic left heart syndrome. Eight patients had thrombotic events post Fontan
      surgery at a median age of 9 years (IQR 5.6-13), 5.7 (IQR 2.0-9.7) years
      following surgery, not including events that occurred immediately peri
      operatively. Four thrombotic events were intracardiac whereas the remainder were
      extra-cardiac. There was no significant univariate correlation between thrombosis
      and the presence of ventricular morphology, pulmonary arterial reconstruction, or
      type of cavopulmonary anastomosis (lateral tunnel vs. extracardiac conduit).
      Thrombosis continues to be an important intermediate-term risk even for patients
      with contemporary Fontan circulations. These results strongly suggest that
      thrombophilic risk is not dictated purely by vascular pathway and hemodynamic
      variables. Further investigation into the pathophysiology, individualized risk,
      and effectiveness of anticoagulation strategies are required in this high risk
      population.

PMID- 28761996
TI  - Discrepancy between in vivo and in vitro comparisons of forced oscillation
      devices.
AB  - The forced oscillation technique (FOT) is an emerging clinical lung function
      test, with commercial devices becoming increasingly available. However
      comparability across existing devices has not been established. We evaluated in
      vivo and in vitro measurements made using three commercial devices against a
      custom-built device (WIMR): Resmon Pro Diary (Restech srl, Italy), tremoFlo C-100
      (Thorasys Medical Systems, Canada), Jaeger Masterscope CT IOS (CareFusion,
      Hoechberg, Germany). Respiratory system resistance Rrs and reactance Xrs at 5 Hz
      were examined in twelve healthy subjects (mean age 33 +/- 11 years, 7 males), and
      in two test standards of known resistance and reactance. Subjects performed three
      measurements during tidal breathing on the four devices in random order. Total,
      inspiratory and expiratory Rrs and Xrs were calculated and compared using one-way
      repeated measures ANOVA and Bonferroni post-hoc tests. Rrs did not differ between
      devices, with <10% deviation from predicted, except for the IOS device. With Xrs,
      similar values were seen between the WIMR and Resmon devices and between the
      tremoFlo and IOS devices. No differences were observed using test standards;
      deviation from theoretical value was <2% for resistance and <5% for reactance.
      The WIMR, tremoFlo and Resmon Pro but not IOS devices measure similar Rrs,
      whereas there was more disparity across devices in the estimation of Xrs
      parameters. The discrepancy between in vivo and in vitro measurements suggest
      that FOT validation procedures need to take into account the breathing pattern,
      either using biological controls or a breathing model.

PMID- 28761997
TI  - Determinants of satisfaction following total hip arthroplasty in patients with
      ankylosing spondylitis.
AB  - BACKGROUND: The aim was to explore the factors contributing to a high degree of
      satisfaction following total hip arthroplasty in patients with ankylosing
      spondylitis and hip joint fusion. METHODS: From January 2001 to June 2015, 43
      patients with ankylosing spondylitis were treated with total hip arthroplasty.
      The patients were divided into two groups, including 20 patients in non-fusion
      groups, with 25 cases of hip non-fusion, and 23 patients in fusion groups, with
      40 cases of hip fusion. Patients were followed for an average of 27 months.
      Harris hip scores (HHSs) and Barthel scores were recorded pre-operatively and
      post-operatively. The improvement rates of both groups were calculated, and the
      data were compared and analyzed. The Self-Administered Patient Satisfaction Scale
      (SAPS) was used to assess the degree of satisfaction in each group. RESULTS: The
      post-operative HHS and Barthel scores of two groups both significantly improved.
      In non-fusion groups compared with fusion groups, there were significant
      differences in the pre-operative HHSs, the improvement of the HHSs, the pre
      operative Barthel score, the improvement of the Barthel score, and the
      satisfaction score. However, there were no significant differences in the post
      operative HHSs and Barthel scores. CONCLUSION: Patients in the hip fusion group
      had higher satisfaction scores. The improvements in joint function and self-care
      ability after total hip arthroplasty are the decisive factors in determining
      patient satisfaction for patients with ankylosing spondylitis combined with hip
      fusion.

PMID- 28761998
TI  - Enzymatic laundry for old clothes: immobilized alpha-amylase from Bacillus sp.
      for the biocleaning of an ancient Coptic tunic.
AB  - The classification and conservation of ancient artworks (belonging to
      collections) is of important cultural, historical, and economic concern. However,
      ancient textiles often display structural damage that renders them fragile and
      unsuitable for exhibition. One of the most common types of damage is linked to
      erroneous restoration treatments, among which the application of glues to
      consolidate cuts. Harsh strategies, such as mechanical or chemical treatments,
      are not suitable since they can cause further impairment of the fabric, whereas
      mild approaches, like wet cleaning, are often ineffective, as also demonstrated
      by the present study. Here, we have explored the possibility of using gellan
      immobilized enzymes of bacterial origin (Bacillus alpha-amylase) to obtain a
      satisfactory starch removal from a damaged archaeological tunic-shroud from the
      Turin Egyptian Museum (Italy), without altering the original yarns or textile
      fibers. This method, already applied to clean casein-damaged wall paintings, as
      well as cotton, silk, and linen fabrics, has proved to be optimal for the
      treatment of a wool burial shroud and to be able to definitively solve fragile
      textile restoration problems. Moreover, efforts have been made to obtain insights
      into the artwork: a multidisciplinary approach has allowed to obtain a correct
      chronological attribution (radiocarbon dating) and fabric fiber characterization
      (SEM-EDX) as well as shed light on the colored parts and dark stains (FORS+IRFC
      and XRF). Finally, the evaluation of the type of glue, by Fourier transform
      infrared spectroscopy, has suggested the best enzyme for glue removal. These
      results have demonstrated that a mild bio-based approach is a successful tool for
      the treatment of archaeological textiles in critical conditions.

PMID- 28761999
TI  - Expression of chondroitin-4-O-sulfotransferase in Escherichia coli and Pichia
      pastoris.
AB  - Chondroitin sulfates are linear sulfated polysaccharides called
      glycosaminoglycans. They are important nutraceutical and pharmaceutical products
      that are biosynthesized through the action of chondroitin sulfotransferases on
      either an unsulfated chondroitin or a dermatan polysaccharide precursor. While
      the enzymes involved in the biosynthesis of chondroitin sulfates are well known,
      the cloning end expression of these membrane-bound Golgi enzymes continue to pose
      challenges. The major chondroitin-4-sulfotransferase, Homo sapiens C4ST-1, had
      been previously cloned and expressed from mammalian CHO, COS-7, and HEK 293
      cells, and its activity was shown to require glycosylation. In the current study,
      a C4ST-1 construct was designed and expressed in both Escherichia coli and Pichia
      pastoris in its non-glycosylated and glycosylated forms. Both constructs showed
      similar activity albeit different kinetic parameters when acting on a microbially
      prepared unsulfated chondroitin substrate. Moreover, the glycosylated form of
      C4ST-1 showed lower stability than the non-glycosylated form.

PMID- 28762000
TI  - Production of omega3 fatty acids in marine cyanobacterium Synechococcus sp.
      strain NKBG 15041c via genetic engineering.
AB  - Omega-3 fatty acids (omega3 FAs) have attracted attention because they have
      various health benefits for humans. Fish oils are currently major sources of
      omega3 FAs, but a sustainable supply of omega3 FAs based on fish oils is
      problematic because of the increasing demand. In this study, the production
      potential of a genetically engineered marine cyanobacterium, Synechococcus sp.
      strain NKBG 15041c, was examined as an alternative source of omega3 FAs. A change
      in fatty acid composition of this cyanobacterium was successfully induced by the
      expression of a heterologous Delta6-desaturase, and the transformants synthesized
      stearidonic acid, which the wild type cannot produce. As a result of optimization
      of culture conditions, maximal contents of stearidonic acid and total omega3 FAs
      reached 12.2 +/- 2.4 and 118.1 +/- 3.5 mg/g, respectively. The maximal omega3 FA
      productivity was 4.6 +/- 0.7 mg/(L?day). These are the highest values of the
      contents of stearidonic acid and omega3 FAs in genetically engineered
      cyanobacteria reported thus far. Therefore, genetically engineered Synechococcus
      sp. strain NKBG 15041c may be a promising sustainable source of omega3 fatty
      acids.

PMID- 28762001
TI  - High-grain diets altered rumen fermentation and epithelial bacterial community
      and resulted in rumen epithelial injuries of goats.
AB  - This study evaluated the effects of high-grain diets on the rumen fermentation,
      epithelial bacterial community, morphology of rumen epithelium, and local
      inflammation of goats during high-grain feeding. Twelve 8-month-old goats were
      randomly assigned to two different diets, a hay diet or a high-grain diet (65%
      grain, HG). At the end of 7 weeks of treatment, samples of rumen content and
      rumen epithelium were collected. Rumen pH was lower (P < 0.05), but the levels of
      volatile fatty acids and lipopolysaccharides were higher (P < 0.05) in the HG
      group than those in the hay group. The principal coordinate analysis indicated
      that HG diets altered the rumen epithelial bacterial community, with an increase
      in the proportion of genus Prevotella and a decrease in the relative abundance of
      the genera Shuttleworthia and Fibrobacteres. PICRUSt analysis suggested that the
      HG-fed group had a higher (P < 0.05) relative abundance of gene families related
      to energy metabolism; folding, sorting, and degradation; translation; metabolic
      diseases; and immune system. Furthermore, HG feeding resulted in the rumen
      epithelial injury and upregulated (P < 0.05) the gene expressions of IL-1beta and
      IL-6, and the upregulations were closely related to the rumen pH, LPS level, and
      rumen epithelial bacteria abundance. In conclusion, our results indicated that
      the alterations in the rumen environment and epithelial bacterial community which
      were induced by HG feeding may result in the damage and local inflammation in the
      rumen epithelium, warranting further study of rumen microbial-host interactions
      in the HG feeding model.

PMID- 28762002
TI  - Development of a bifunctional xylanase-cellulase chimera with enhanced activity
      on rice and barley straws using a modular xylanase and an endoglucanase procured
      from camel rumen metagenome.
AB  - The camel rumen metagenome is an untapped source of glycoside hydrolases. In this
      study, novel genes encoding for a modular xylanase (XylC) and a cellulase (CelC)
      were isolated from a camel rumen metagenome and expressed in Escherichia coli
      BL21 (DE3). XylC with xylanase (Xyn), CBM, and carbohydrate esterase (CE) domains
      was characterized as a beta-1,4-endoxylanase with remarkable catalytic activity
      on oat-spelt xylan (K cat = 2919 +/- 57 s-1). The implication of XylC's modular
      structure in its high catalytic activity was analyzed by truncation and fusion
      construction with CelC. The resulting fusions including Cel-CBM, Cel-CBM-CE, and
      Xyn-CBM-Cel showed remarkable enhancement in CMCase activity with K cat values of
      742 +/- 12, 1289 +/- 34.5, and 2799 +/- 51 s-1 compared to CelC with a K cat of
      422 +/- 3.5 s-1. It was also shown that the bifunctional Xyn-CBM-Cel with
      synergistic xylanase/cellulase activities was more efficient than XylC and CelC
      in hydrolysis of rice and barley straws.

PMID- 28762003
TI  - Chemical Heterogeneity in Inbred European Population of the Invasive Hornet Vespa
      velutina nigrithorax.
AB  - Invasive social insect populations that have been introduced to a new environment
      through a limited number of introduction events generally exhibit reduced
      variability in their chemical signatures (cuticular hydrocarbons) compared to
      native populations of the same species. The reduced variability in these major
      recognition cues could be caused by a reduction of genetic diversity due to a
      genetic bottleneck. This hypothesis was tested in an inbred European population
      of the invasive hornet Vespa velutina nigrithorax. Our results show that, in
      spite of the limited amount of genetic diversity present in the European
      population, the chemical signatures of individuals were highly heterogeneous
      according to their caste, sex, and colony origin. In queens, some specific
      saturated and unsaturated hydrocarbons were identified. These results suggest
      that epigenetic and/or environmental factors could play a role in modifying
      cuticular hydrocarbon profiles in this introduced hornet population despite the
      observed reduction of genetic diversity.

PMID- 28762005
TI  - A Web-based searchable system to confirm magnetic resonance compatibility of
      implantable medical devices in Japan: a preliminary study.
AB  - Confirmation of the magnetic resonance (MR) compatibility of implanted medical
      devices (IMDs) is mandatory before conducting magnetic resonance imaging (MRI)
      examinations. In Japan, few such confirmation methods are in use, and they are
      time-consuming. This study aimed to develop a Web-based searchable MR safety
      information system to confirm IMD compatibility and to evaluate the usefulness of
      the system. First, MR safety information for intravascular stents and stent
      grafts sold in Japan was gathered by interviewing 20 manufacturers. These IMDs
      were categorized based on the descriptions available on medical package inserts
      as: "MR Safe," "MR Conditional," "MR Unsafe," "Unknown," and "No Medical Package
      Insert Available". An MR safety information database for implants was created
      based on previously proposed item lists. Finally, a Web-based searchable system
      was developed using this database. A questionnaire was given to health-care
      personnel in Japan to evaluate the usefulness of this system. Seventy-nine
      datasets were collected using information provided by 12 manufacturers and by
      investigating the medical packaging of the IMDs. Although the datasets must be
      updated by collecting data from other manufacturers, this system facilitates the
      easy and rapid acquisition of MR safety information for IMDs, thereby improving
      the safety of MRI examinations.

PMID- 28762004
TI  - GBM radiosensitizers: dead in the water...or just the beginning?
AB  - The finding that most GBMs recur either near or within the primary site after
      radiotherapy has fueled great interest in the development of radiosensitizers to
      enhance local control. Unfortunately, decades of clinical trials testing a wide
      range of novel therapeutic approaches have failed to yield any clinically viable
      radiosensitizers. However, many of  the previous radiosensitizing strategies were
      not based on clear pre-clinical evidence, and in many cases blood-barrier
      penetration was not considered. Furthermore, DNA repair inhibitors have only
      recenly arrived in the clinic, and likely represent potent agents for glioma
      radiosensitization. Here, we present recent progress in the use of small molecule
      DNA damage response inhibitors as GBM radiosensitizers. In addition, we discuss
      the latest progress in targeting hypoxia and oxidative stress for GBM
      radiosensitization.

PMID- 28762006
TI  - Oleaginous Microalgae from Dairy Farm Wastewater for Biodiesel Production:
      Isolation, Characterization and Mass Cultivation.
AB  - Producing biodiesel from microalgae grown in wastewater is environment-friendly
      and cost-effective. The present study investigated the algae found in wastewater
      of a local dairy farm for their potential as biodiesel feedstocks. Thirteen
      native algal strains were isolated. On the basis of morphology and 16S/18S rRNA
      gene sequences, one strain was identified to be a member of cyanobacteria, while
      other 12 strains belong to green algae. After screening, two Scenedesmus strains
      out of the 13 microalgae isolates demonstrated superiority in growth rate, lipid
      productivity, and sedimentation properties, and therefore were selected for
      further scale-up outdoor cultivation. Both Scenedesmus strains quickly adapted to
      the outdoor conditions, exhibiting reasonably good growth and strong anti
      contamination capabilities. In flat-plate photobioreactors (PBRs), algal cells
      accumulated predominantly neutral lipids that accounted for over 60% of total
      lipids with almost 70% being triacylglycerol. In addition, Scenedesmus obliquus
      had a high content of monounsaturated fatty acids, of which the amount of oleic
      acid (C18:1) was up to 27.11%. Based on these findings, the dairy farm wastewater
      isolated Scenedesmus strains represent promising sources of low-cost, high
      quality oil for biofuel production.

PMID- 28762007
TI  - Optimization of Enzyme Co-Immobilization with Sodium Alginate and Glutaraldehyde
      Activated Chitosan Beads.
AB  - In this study, two different materials-alginate and glutaraldehyde-activated
      chitosan beads-were used for the co-immobilization of alpha-amylase, protease,
      and pectinase. Firstly, optimization of multienzyme immobilization with Na
      alginate beads was carried out. Optimum Na alginate and CaCl2 concentration were
      found to be 2.5% and 0.1 M, respectively, and optimal enzyme loading ratio was
      determined as 2:1:0.02 for pectinase, protease, and alpha-amylase, respectively.
      Next, the immobilization of multiple enzymes on glutaraldehyde-activated chitosan
      beads was optimized (3% chitosan concentration, 0.25% glutaraldehyde with 3 h of
      activation and 3 h of coupling time). While co-immobilization was successfully
      performed with both materials, the specific activities of enzymes were found to
      be higher for the enzymes co-immobilized with glutaraldehyde-activated chitosan
      beads. In this process, glutaraldehyde was acting as a spacer arm. SEM and FTIR
      were used for the characterization of activated chitosan beads. Moreover,
      pectinase and alpha-amylase enzymes immobilized with chitosan beads were also
      found to have higher activity than their free forms. Three different enzymes were
      co-immobilized with these two materials for the first time in this study.

PMID- 28762008
TI  - An evaluation of social work services in a cancer accommodation facility for
      rural South Australians.
AB  - PURPOSE: The purpose of this investigation was to evaluate the social work
      service at an accommodation facility for people receiving cancer treatment away
      from home with a focus on distress, impact of support, and type of assistance
      received from the social work service. METHOD: Guests who stayed at the Cancer
      Council Lodge during June 2015 were mailed a questionnaire collecting information
      about level of distress upon arrival and departure, impact of support in several
      areas, and what the service assisted them with specifically. RESULTS: The sample
      comprised 149 guests. Social work contact (n = 19) was associated with greater
      reduction in distress between arrival and departure compared with no contact (n =
      56). Contact with a social worker was associated with greater odds of agreeing or
      strongly agreeing that guests felt supported in 6 out of 10 areas assessed. These
      areas were managing the challenges related to cancer, approaching support
      services, asking questions of healthcare teams, accessing support services,
      coping with strong emotions, and understanding reactions of family and friends.
      The most common types of support received were emotional and informational
      support. CONCLUSIONS: This study describes some of benefits of providing social
      work services to people receiving cancer treatment away from home and has
      implications for provision of social work service resources in similar settings.
      Further research could investigate the impact of this service in similar settings
      using randomised controlled trials to better account for potential biases.
      Research in this area has potential to inform program development and policy.

PMID- 28762009
TI  - A fed-batch strategy to produce high poly(3-hydroxybutyrate-co-3-hydroxyvalerate
      co-4-hydroxybutyrate) terpolymer yield with enhanced mechanical properties in
      bioreactor.
AB  - This study reports an efficient fed-batch strategy to improve poly(3
      hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate) [P(3HB-co-3HV-co-4HB)]
      terpolymer production by Cupriavidus sp. USMAA2-4 with enhanced mechanical
      properties in bioreactor. The cultivations have been performed by combining oleic
      acid with gamma-butyrolactone at different concentration ratios with 1-pentanol
      at a fixed concentration. The batch and fed-batch fermentations have resulted in
      P(3HB-co-3HV-co-4HB) with compositions of 9-35 mol% 3HV and 4-24 mol% 4HB
      monomers. The DO-stat fed-batch fermentation strategies have significantly
      improved the production with a maximum 4.4-fold increment of cell dry weight
      (CDW). Besides, appropriate feeding of the substrates has resulted in an
      increment of terpolymer productivity from 0.086-0.347 g/L/h, with a significantly
      shortened cultivation time. The bacterial growth and terpolymer formation have
      been found to be affected by the concentration of carbon sources supplied.
      Characterization of P(3HB-co-3HV-co-4HB) has demonstrated that incorporation of
      3HV and 4HB monomer has significantly improved the physical and thermodynamic
      properties of the polymers, by reducing the polymer's crystallinity. The tensile
      strength, Young's modulus of the terpolymer has been discovered to increase with
      the increase of M w. The fed-batch fermentation strategies employed in this study
      have resulted in terpolymers with a range of flexible materials having improved
      tensile strength and Young's modulus as compared to the terpolymer produced from
      batch fermentation. Possession of lower melting temperature indicates an enhanced
      thermal stability which broadens the polymer processing window.

PMID- 28762010
TI  - Clinical and pathological characterization of HER2 mutations in human breast
      cancer: a systematic review of the literature.
AB  - PURPOSE: HER2 gene is a member of the epidermal growth factor receptor (EGFR)
      family. Across different malignancies, aberrations of HER2 gene commonly
      correspond to gain-of-function alterations leading to increased receptor
      signaling. METHODS: We have reviewed the literature currently available on HER2
      mutations in human breast cancer (BC) evaluating type and frequency of such
      mutations. The primary objective was to determine the frequency and the number of
      patients with HER2-mut in the series analyzed. The secondary objectives were to
      assess characteristics of mutated cases (ER and HER2 status and stage of disease,
      type of mutations, and finally the clinical outcome if reported). RESULTS: We
      retrieved 31 published papers, and the pooled rate of HER2 mutations across
      12,905 BC patients was calculated. Overall, the frequency of HER2 mutations was
      2.7% with most involving the intracellular domain. About 4% of patients were
      finally mutated. The predictive role was not described. Only 30% of these
      patients were simultaneously HER2 positive and 63% were ER positive. CONCLUSION:
      We have found that the prevalence of HER2 mutations is about 3%. These genic
      alterations are independently associated with HER2 amplification status,
      occurring in both ER-positive/HER2-negative diseases or HER2-enriched cancers.
      Ongoing trials are investigating small molecules tyrosine kinase inhibitors in
      patients harboring these mutations.

PMID- 28762011
TI  - Erratum to: Pro-apoptotic effect of Delta2-TGZ in "claudin-1-low" triple-negative
      breast cancer cells: involvement of claudin-1.

PMID- 28762012
TI  - Cross-cultural comparison of breast cancer patients' Quality of Life in the
      Netherlands and Japan.
AB  - PURPOSE: Cultural differences are hypothesized to influence patients' Quality of
      Life (QoL) reports. However, there is a lack of empirical cross-cultural studies
      comparing QoL of patients with cancer. This study aims to compare QoL of women
      with breast cancer in the Netherlands and Japan, and to investigate the
      association of QoL with sociodemographic, clinical, and psychological variables
      (illness perceptions). METHODS: Dutch (n = 116) and Japanese (n = 148) women with
      early breast cancer undergoing chemotherapy completed the EORTC QLQ-C30 and Brief
      Illness Perception Questionnaire immediately before their second cycle of
      chemotherapy. RESULTS: Dutch women reported poorer Physical, Role, Emotional, and
      Cognitive functioning than Japanese women. Additionally, illness perceptions were
      significantly different in Japan and the Netherlands, but these did not vary
      across treatment type. In Japan, QoL of women receiving AC-chemotherapy was
      better than that of women receiving FEC-chemotherapy, whereas in the Netherlands,
      QoL did not vary as a function of chemotherapy. Illness perceptions about symptom
      severity, adverse consequences, and emotional representations were negatively
      related to most domains of patients' QoL in both countries. Adding illness
      perceptions as covariates to the ANOVA analyses rendered the effects of country
      and treatment type on QoL non-significant. CONCLUSIONS: Comparing Dutch and
      Japanese women with early breast cancer revealed important differences in
      treatment modalities and illness perceptions which both appear to influence QoL.
      Perceptions about cancer have been found to vary across cultures, and our study
      suggests that these perceptions should be considered when performing cross
      cultural studies focusing on patient-reported outcomes.

PMID- 28762013
TI  - The role of microRNAs in different types of thyroid carcinoma: a comprehensive
      analysis to find new miRNA supplementary therapies.
AB  - The most common endocrine malignancy is thyroid cancer, and researchers have made
      a great deal of progress in deciphering its molecular mechanisms in the recent
      years. Many of molecular changes observed in thyroid cancer can be used as
      biomarkers for diagnosis, prognosis, and therapeutic targets for treatment.
      MicroRNAs (miRNAs) are important parts in biological and metabolic pathways such
      as regulation of developmental stages, signal transduction, cell maintenance, and
      differentiation. Therefore, their dysregulation can expose individuals to
      malignancies. It has been proved that miRNA expression is dysregulated in
      different types of tumors, like thyroid cancers, and can be the cause of tumor
      initiation and progression. In this paper, we have reviewed the available data on
      miRNA dysregulation in different thyroid tumors including papillary, follicular,
      anaplastic, and medullary thyroid carcinomas aiming to introduce the last updates
      in miRNAs-thyroid cancer relation.

PMID- 28762015
TI  - Using Genomic Information to Guide Ibrutinib Treatment Decisions in Chronic
      Lymphocytic Leukaemia: A Cost-Effectiveness Analysis.
AB  - BACKGROUND: Genomic tests may improve the stratification of patients to receive
      new therapies in several disease areas. However, the use of expensive targeted
      therapies can impact on the cost effectiveness of these tests. This study
      presents an economic evaluation of genomic testing in chronic lymphocytic
      leukaemia in the context of the UK National Health Service. METHODS: Cost
      effectiveness and cost-utility analyses (using life-years and quality-adjusted
      life-years) were undertaken from a National Health Service and societal
      perspective. Five strategies were evaluated across several age groups using
      Markov modelling: three strategies that reflected varying current genetic testing
      practice and two configurations of genomic testing (including ibrutinib
      treatment). RESULTS: Genomic testing strategies yielded the most life
      years/quality-adjusted life-years per patient, but were not cost effective
      compared with a threshold of L30,000 per life-year/quality-adjusted life-year
      gained. Cost-effectiveness acceptability curves indicated that there was some
      uncertainty surrounding this result. A genomic testing strategy becomes the most
      cost-effective option if a higher end-of-life cost-effectiveness threshold of
      L50,000 is applied, if a societal costing perspective is considered in 25-year
      old patients or if the cost of ibrutinib treatment falls. CONCLUSION: Stratifying
      patients with chronic lymphocytic leukaemia to targeted treatment using genomic
      testing improves health outcomes, but will likely only represent a cost-effective
      use of limited National Health Service resources if a higher cost-effectiveness
      threshold or societal costing perspective is applied, or if the price of
      ibrutinib treatment is reduced. This result may be broadly indicative of the
      likely cost effectiveness of other genomic tests that inform the stratification
      of patients to high cost-targeted therapies.

PMID- 28762014
TI  - Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms
      of chemoprevention.
AB  - After more than a century, aspirin remains one of the most commonly used drugs in
      western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and
      analgesic properties, a multitude of clinical studies have provided convincing
      evidence that regular, low-dose aspirin use dramatically lowers the risk of
      cancer. These observations coincide with recent studies showing a functional
      relationship between platelets and tumors, suggesting that aspirin's
      chemopreventive properties may result, in part, from direct modulation of
      platelet biology and biochemistry. Here, we present a review of the biochemistry
      and pharmacology of aspirin with particular emphasis on its cyclooxygenase
      dependent and cyclooxygenase-independent effects in platelets. We also correlate
      the results of proteomic-based studies of aspirin acetylation in eukaryotic cells
      with recent developments in platelet proteomics to identify non-cyclooxygenase
      targets of aspirin-mediated acetylation in platelets that may play a role in its
      chemopreventive mechanism.

PMID- 28762016
TI  - ICA-based muscle-tendon units localization and activation analysis during dynamic
      motion tasks.
AB  - This study proposed an independent component analysis (ICA)-based framework for
      localization and activation level analysis of muscle-tendon units (MTUs) within
      skeletal muscles during dynamic motion. The gastrocnemius muscle and extensor
      digitorum communis were selected as target muscles. High-density electrode arrays
      were used to record surface electromyographic (sEMG) data of the targeted muscles
      during dynamic motion tasks. First, the ICA algorithm was used to decompose multi
      channel sEMG data into a weight coefficient matrix and a source matrix. Then, the
      source signal matrix was analyzed to determine EMG sources and noise sources. The
      weight coefficient vectors corresponding to the EMG sources were mapped to target
      muscles to find the location of the MTUs. Meanwhile, the activation level changes
      in MTUs during dynamic motion tasks were analyzed based on the corresponding EMG
      source signals. Eight subjects were recruited for this study, and the
      experimental results verified the feasibility and practicality of the proposed
      ICA-based method for the MTUs' localization and activation level analysis during
      dynamic motion. This study provided a new, in-depth way to analyze the functional
      state of MTUs during dynamic tasks and laid a solid foundation for MTU-based
      accurate muscle force estimation, muscle fatigue prediction, neuromuscular
      control characteristic analysis, etc.

PMID- 28762017
TI  - A GPU-based symmetric non-rigid image registration method in human lung.
AB  - Quantitative computed tomography (QCT) of the lungs plays an increasing role in
      identifying sub-phenotypes of pathologies previously lumped into broad categories
      such as chronic obstructive pulmonary disease and asthma. Methods for image
      matching and linking multiple lung volumes have proven useful in linking
      structure to function and in the identification of regional longitudinal changes.
      Here, we seek to improve the accuracy of image matching via the use of a
      symmetric multi-level non-rigid registration employing an inverse consistent (IC)
      transformation whereby images are registered both in the forward and reverse
      directions. To develop the symmetric method, two similarity measures, the sum of
      squared intensity difference (SSD) and the sum of squared tissue volume
      difference (SSTVD), were used. The method is based on a novel generic
      mathematical framework to include forward and backward transformations,
      simultaneously, eliminating the need to compute the inverse transformation. Two
      implementations were used to assess the proposed method: a two-dimensional (2-D)
      implementation using synthetic examples with SSD, and a multi-core CPU and
      graphics processing unit (GPU) implementation with SSTVD for three-dimensional (3
      D) human lung datasets (six normal adults studied at total lung capacity (TLC)
      and functional residual capacity (FRC)). Success was evaluated in terms of the IC
      transformation consistency serving to link TLC to FRC. 2-D registration on
      synthetic images, using both symmetric and non-symmetric SSD methods, and
      comparison of displacement fields showed that the symmetric method gave a
      symmetrical grid shape and reduced IC errors, with the mean values of IC errors
      decreased by 37%. Results for both symmetric and non-symmetric transformations of
      human datasets showed that the symmetric method gave better results for IC errors
      in all cases, with mean values of IC errors for the symmetric method lower than
      the non-symmetric methods using both SSD and SSTVD. The GPU version demonstrated
      an average of 43 times speedup and ~5.2 times speedup over the single-threaded
      and 12-threaded CPU versions, respectively. Run times with the GPU were as fast
      as 2 min. The symmetric method improved the inverse consistency, aiding the use
      of image registration in the QCT-based evaluation of the lung.

PMID- 28762018
TI  - Uprooted Phylogenetic Networks.
AB  - The need for structures capable of accommodating complex evolutionary signals
      such as those found in, for example, wheat has fueled research into phylogenetic
      networks. Such structures generalize the standard model of a phylogenetic tree by
      also allowing for cycles and have been introduced in rooted and unrooted form. In
      contrast to phylogenetic trees or their unrooted versions, rooted phylogenetic
      networks are notoriously difficult to understand. To help alleviate this, recent
      work on them has also centered on their "uprooted" versions. By focusing on such
      graphs and the combinatorial concept of a split system which underpins an
      unrooted phylogenetic network, we show that not only can a so-called (uprooted) 1
      nested network N be obtained from the Buneman graph (sometimes also called a
      median network) associated with the split system [Formula: see text] induced on
      the set of leaves of N but also that that graph is, in a well-defined sense,
      optimal. Along the way, we establish the 1-nested analogue of the fundamental
      "splits equivalence theorem" for phylogenetic trees and characterize maximal
      circular split systems.

PMID- 28762020
TI  - Conception and Management of a Poorly Understood Spectrum of Dermatologic
      Neoplasms: Atypical Fibroxanthoma, Pleomorphic Dermal Sarcoma, and
      Undifferentiated Pleomorphic Sarcoma.
AB  - OPINION STATEMENT: Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma
      (PDS) tumors share many clinical, etiologic, and histologic features and likely
      represent components of a tumor spectrum. In dermatologic oncology,
      differentiating between AFX and PDS is pivotal as tumors with histological
      features consistent with PDS are more likely to behave in a clinically aggressive
      manner. Importantly, the term "pleomorphic dermal sarcoma" (PDS) is a more
      appropriate designation than "undifferentiated pleomorphic sarcoma" (UPS) for
      describing deeper, more aggressive, histologically high-grade cutaneous tumors
      that otherwise resemble AFX. Surgery remains the gold standard for treatment. In
      the setting of AFX, excision with the Mohs micrographic technique appears to
      offer superior tumor control rates while maintaining greater tissue preservation
      over wide local excision and should be considered first line. In the setting of
      PDS, optimal management is less clear given the paucity of available data.
      However, due to its greater propensity to recur and metastasize, extirpation with
      complete tumor margin control appears paramount. The roles of imaging and SLNB in
      management and clinical outcomes of AFX and PDS are unclear given the lack of
      available data. In reality, these tools are unlikely to be helpful in most cases
      of AFX. However, in the setting of PDS, emerging literature indicates that these
      tumors are inherently higher risk, and thus, imaging and SLNB may be helpful in
      select cases. Additionally, radiation therapy may be of adjuvant benefit for
      these tumors when clear surgical margins cannot be obtained. While traditional
      chemotherapy has been largely ineffectual, the recent discovery of key
      oncogenetic mutations has allowed for the identification of several potential
      molecular drug targets that may have a therapeutic role with future study. In the
      unfortunate setting of metastatic disease, a multidisciplinary approach is
      optimal. Further studies are needed to establish definitive conclusions regarding
      risk stratification and best management practices.

PMID- 28762019
TI  - Epicardial adipose tissue as a metabolic transducer: role in heart failure and
      coronary artery disease.
AB  - Obesity and diabetes are strongly associated with metabolic and cardiovascular
      disorders including dyslipidemia, coronary artery disease, hypertension, and
      heart failure. Adipose tissue is identified as a complex endocrine organ, which
      by exerting a wide array of regulatory functions at the cellular, tissue and
      systemic levels can have profound effects on the cardiovascular system. Different
      terms including "epicardial," "pericardial," and "paracardial" have been used to
      describe adipose tissue deposits surrounding the heart. Epicardial adipose tissue
      (EAT) is a unique and multifaceted fat depot with local and systemic effects. The
      functional and anatomic proximity of EAT to the myocardium enables endocrine,
      paracrine, and vasocrine effects on the heart. EAT displays a large secretosome,
      which regulates physiological and pathophysiological processes in the heart.
      Perivascular adipose tissue (PVAT) secretes adipose-derived relaxing factor,
      which is a "cocktail" of cytokines, adipokines, microRNAs, and cellular
      mediators, with a potent effect on paracrine regulation of vascular tone,
      vascular smooth muscle cell proliferation, migration, atherosclerosis
      susceptibility, and restenosis. Although there are various physiological
      functions of the EAT and PVAT, a phenotypic transformation can lead to a major
      pathogenic role in various cardiovascular diseases. The equilibrium between the
      physiological and pathophysiological properties of EAT is very delicate and
      susceptible to the influences of intrinsic and extrinsic factors. Various
      adipokines secreted from EAT and PVAT have a profound effect on the myocardium
      and coronary arteries; targeting these adipokines could be an important
      therapeutic approach to counteract cardiovascular disease.

PMID- 28762021
TI  - Retroverted glenoid reconstruction using glenoid plate in reverse shoulder
      arthroplasty.
AB  - PURPOSE: The objective of this study is to evaluate the clinical and radiological
      results of reverse shoulder arthroplasty (RSA) with glenoid plating in a
      consecutive series of patients affected by cuff tear glenohumeral arthropathy
      with glenoid retroversion >15 degrees . We hypothesized that autologous humeral
      head graft may be better stabilized between the baseplate and the native glenoid
      surface with the use of a glenoid plate. METHODS: Twenty consecutive patients
      affected by cuff tear arthropathy with glenoid retroversion >15 degrees  (B2 or C
      according to Walch classification) were enrolled in this study. To reconstruct
      the glenoid, a dedicated plate was used in addition to the standard reverse
      shoulder baseplate and the glenosphere. Clinical and radiological assessment was
      performed using constant score (CS), subjective shoulder value (SSV), X-rays and
      CT scan at 6, 12 and 24 months of follow-up. Healing and resorption of the graft
      and detection of the glenoid version were assessed. RESULTS: Sixteen patients
      were available for final follow-up. The mean preoperative retroversion of the
      glenoid was 24 degrees , while the post-op was 2 degrees  (p = 0.002). At 24
      months of follow-up, mean CS and SSV were 61 and 70. Respect to preoperative
      scores, the results were statistically significant (p < 0.001). The last CT scan
      revealed: a complete healing of the graft in 100% of cases; graft resorption less
      than 25% in two patients (12.5%); glenoid retroversion of 4 degrees . A negative
      statistically significant correlation was found between final CS and preoperative
      glenoid retroversion (0.039). CONCLUSIONS: The present study reports the
      favorable outcomes of retroverted glenoid reconstruction with glenoid plates in
      RSA, an alternative method to address severe glenoid deficiency. LEVEL OF
      EVIDENCE: Level IV, case series with no comparison group.

PMID- 28762022
TI  - Optimal duration of dual antiplatelet therapy after percutaneous coronary
      intervention or after acute coronary syndrome : Practical lessons from a review.
AB  - To prevent recurrent ischaemic events, dual antiplatelet therapy (DAPT) is the
      standard of care after percutaneous coronary intervention and in the treatment of
      acute coronary syndrome. Recent evidence supports an adjusted DAPT duration in
      selected patients.The current paper aims to encourage cardiologists to actively
      search for patients benefiting from either shorter or prolonged duration DAPT and
      proposes an algorithm to identify patients who are likely to benefit from such an
      alternative strategy.Individualised DAPT duration should be considered in high
      risk anatomic and/or clinical subgroups or in patients at increased haemorrhagic
      risk with low ischaemic risk. Both thrombotic and haemorrhagic risk should be
      assessed in all patients. In patients undergoing percutaneous coronary
      intervention, the interventional cardiologist could advise on the minimal
      duration of DAPT. However, in contrast to the minimum duration of DAPT for stent
      thrombosis prevention, longer duration DAPT is aimed at prevention of spontaneous
      myocardial infarction, and not at stent thrombosis, and thus the key to success
      is to treat the patient's overall thrombotic risk.The advice on the duration of
      DAPT must be documented in the patient's records and communicated with the
      treating physician and general practitioner. DAPT duration should be reassessed
      at least on a yearly basis.

PMID- 28762023
TI  - Efficacy of Goal-Directed Fluid Therapy via Pleth Variability Index During
      Laparoscopic Roux-en-Y Gastric Bypass Surgery in Morbidly Obese Patients.
AB  - BACKGROUND: There is no well-recognized guideline for intraoperative fluid
      management in bariatric surgery. Goal-directed fluid therapy (GDFT) is a new
      concept of perioperative fluid management which was shown to improve patients'
      prognoses. Dynamic indicators may better predict fluid response compared to
      static indicators. In this study, we aimed to assess effects of administering
      GDFT protocol via Pleth Variability Index (PVI) in morbidly obese patients
      undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. METHODS: The
      study included 60 patients who underwent elective laparoscopic RYGB surgery.
      Subjects were randomized to two groups as being managed with either standard
      fluid regimen (control group) or PVI (PVI group) during intraoperative period.
      After induction of general anesthesia, control group received 500 ml crystalloid
      bolus followed by 4-8 ml/kg/h infusion. Fluid management of the control group was
      guided by central venous pressure and mean arterial pressure. PVI group received
      500 ml crystalloid bolus followed by 2 ml/kg/h infusion. If PVI had been > 14%,
      250 ml colloid was administered. Norepinephrine was given by infusion to keep
      mean arterial pressure > 65 mmHg, if needed. Perioperative lactate levels,
      hemodynamic parameters, and renal functions were recorded. RESULTS: In PVI group,
      volume of crystalloid and total fluid infusion during intraoperative period was
      significantly lower than the control group (p < 0.05). The groups did not
      significantly differ in terms of lactate or creatinine levels before or after the
      surgery (p > 0.05). CONCLUSIONS: There is no need to administer extra volume of
      fluid to obese patients undergoing laparoscopic bariatric surgery. Use of dynamic
      indicators like PVI helps to decrease intraoperative volume of infused fluids
      with no effects on either intraoperative or postoperative lactate levels in
      laparoscopic bariatric interventions.

PMID- 28762025
TI  - Erratum to: Abstracts from the 22nd World Congress of the International
      Federation for the Surgery of Obesity & Metabolic Disorders (IFSO), London, 29
      August - 2 September 2017.

PMID- 28762024
TI  - Risk Factors for Prolonged Length of Hospital Stay and Readmissions After
      Laparoscopic Sleeve Gastrectomy and Laparoscopic Roux-en-Y Gastric Bypass.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) and laparoscopic gastric bypass
      (LRYGB) are most commonly performed bariatric procedures. Laparoscopic approach
      and enhanced recovery after surgery (ERAS) protocols managed to decrease length
      of hospital and morbidity. However, there are patients in whom, despite adherence
      to the protocol, the length of stay (LOS) remains longer than targeted. This
      study aimed to assess potential risk factors for prolonged LOS and readmissions.
      METHODS: The study was a prospective observation with a post-hoc analysis of
      bariatric patients in a tertiary referral university teaching hospital. Inclusion
      criteria were undergoing laparoscopic bariatric surgery. Exclusion criteria were
      occurrence of perioperative complications, prior bariatric procedures, and lack
      of necessary data. The primary endpoints were the evaluations of risk factors for
      prolonged LOS and readmissions. RESULTS: Median LOS was 3 (2-4) days. LOS > 3
      days occurred in 145 (29.47%) patients, 79 after LSG (25.82%) and 66 after LRYGB
      (35.48%; p = 0.008). Factors significantly prolonging LOS were low oral fluid
      intake, high intravenous volume of fluids administered on POD0, and every
      additional 50 km distance from habitual residence to bariatric center. The risk
      of hospital readmission rises with occurrence of intraoperative adverse events
      and low oral fluid intake on the day of surgery on. CONCLUSIONS: Risk factors for
      prolonged LOS are low oral fluid intake, high intravenous volume of fluids
      administered on POD0, and every additional 50 km distance from habitual
      residence. Risk factors for hospital readmission are intraoperative adverse
      events and low oral fluid intake on the day of surgery.

PMID- 28762026
TI  - Feasibility of 3D printed air slab diode caps for small field dosimetry.
AB  - Commercial diode detectors used for small field dosimetry introduce a field-size
      dependent over-response relative to an ideal, water-equivalent dosimeter due to
      high density components in the body of the detector. An air gap above the
      detector introduces a field-size-dependent under-response, and can be used to
      offset the field-size-dependent detector over-response. Other groups have
      reported experimental validation of caps containing air gaps for use with several
      types of diodes in small fields. This paper examines two designs for 3D printed
      diode air caps for the stereotactic field diode (SFD)-a cap containing a sealed
      air cavity, and a cap with an air cavity at the face of the SFD. Monte Carlo
      simulations of both designs were performed to determine dimensions for an air
      cavity to introduce the desired dosimetric correction. Various parameter changes
      were also simulated to estimate the dosimetric uncertainties introduced by 3D
      printing. Cap layer dimensions, cap density changes due to 3D printing, and
      unwanted air gaps were considered. For the sealed design the optimal air gap size
      for water-equivalent cap material was 0.6 mm, which increased to 1.0 mm when
      acrylonitrile butadiene styrene in the cap was simulated. The unsealed design had
      less variation, a 0.4 mm air gap is optimal in both situations. Unwanted air
      pockets in the bore of the cap and density changes introduced by the 3D printing
      process can potentially introduce significant dosimetric effects. These effects
      may be limited by using fine print resolutions and minimising the volume of cap
      material.

PMID- 28762027
TI  - A simple and efficient algorithm operating with linear time for MCEEG data
      compression.
AB  - Popularisation of electroencephalograph (EEG) signals in diversified fields have
      increased the need for devices capable of operating at lower power and storage
      requirements. This has led to a great deal of research in data compression, that
      can address (a) low latency in the coding of the signal, (b) reduced hardware and
      software dependencies, (c) quantify the system anomalies, and (d) effectively
      reconstruct the compressed signal. This paper proposes a computationally simple
      and novel coding scheme named spatial pseudo codec (SPC), to achieve lossy to
      near lossless compression of multichannel EEG (MCEEG). In the proposed system,
      MCEEG signals are initially normalized, followed by two parallel processes: one
      operating on integer part and the other, on fractional part of the normalized
      data. The redundancies in integer part are exploited using spatial domain
      encoder, and the fractional part is coded as pseudo integers. The proposed method
      has been tested on a wide range of databases having variable sampling rates and
      resolutions. Results indicate that the algorithm has a good recovery performance
      with an average percentage root mean square deviation (PRD) of 2.72 for an
      average compression ratio (CR) of 3.16. Furthermore, the algorithm has a
      complexity of only O(n) with an average encoding and decoding time per sample of
      0.3 ms and 0.04 ms respectively. The performance of the algorithm is comparable
      with recent methods like fast discrete cosine transform (fDCT) and tensor
      decomposition methods. The results validated the feasibility of the proposed
      compression scheme for practical MCEEG recording, archiving and brain computer
      interfacing systems.

PMID- 28762029
TI  - Response biases in simple decision making: Faster decision making, faster
      response execution, or both?
AB  - When people are biased to use one response more often than an alternative
      response in a decision task, they also make the preferred response more quickly.
      Sequential sampling models can accommodate this difference in response time (RT)
      by changing the relative amount of evidence that must accumulate to decide in
      favor of one versus the other response, but nondecision processes might also play
      a role, such as the amount of time between selecting and executing a response. We
      investigated the influence of decision and nondecision processes in two
      experiments. In Experiments 1a and 1b, arrows appeared on the screen, and
      participants were asked to move a joystick in the direction of the arrow or make
      a keypress as quickly as possible. Results showed that motor execution times were
      faster for expected directions than unexpected directions. In Experiments 2a and
      2b, participants decided whether a high or low number of asterisks was displayed
      on the screen. Decision times were faster for the stimulus class that was more
      likely to appear, and this effect was larger when participants could anticipate
      both the likely stimulus class and the motor response needed to identify it than
      when they knew the likely stimulus class but the associated motor response
      changed probabilistically from trial to trial. These results show that both
      decision and nondecision factors contribute to bias effects on RT.

PMID- 28762028
TI  - Word predictability affects saccade length in Chinese reading: An evaluation of
      the dynamic-adjustment model.
AB  - How does a word's within-sentence predictability influence saccade length during
      reading? An eye-movement experiment manipulating the predictability of target
      words indicates that, relative to low-predictability target words, high
      predictability targets elicit longer saccades to themselves. Simulations using
      computational models that respectively instantiate the targeting of saccades to
      default locations (Yan, Kliegl, Richter, Nuthmann, & Shu in Journal of
      Experimental Psychology, 63, 705-725, 2010) versus the dynamic adjustment of
      saccade length (Liu, Reichle, & Li in Journal of Experimental Psychology Learning
      Memory and Cognition, 41, 1229-1236, 2015, Journal of Experimental Psychology:
      Human Perception and Performance, 42, 1008-1025, 2016) indicate that the latter
      model provides a more accurate and parsimonious account of saccade-targeting
      behavior in Chinese reading. The implications of these conclusions are discussed
      with respect to current models of eye-movement control during reading and the
      necessity to explain eye movements in languages as different as Chinese versus
      English.

PMID- 28762030
TI  - A contrastive account of explanation generation.
AB  - In this article, we propose a contrastive account of explanation generation.
      Though researchers have long wrestled with the concepts of explanation and
      understanding, as well as with the procedures by which we might evaluate
      explanations, less attention has been paid to the initial generation stages of
      explanation. Before an explainer can answer a question, he or she must come to
      some understanding of the explanandum-what the question is asking-and of the
      explanatory form and content called for by the context. Here candidate
      explanations are constructed to respond to the particular interpretation of the
      question, which, according to the pragmatic approach to explanation, is
      constrained by a contrast class-a set of related but nonoccurring alternatives to
      the topic that emerge from the surrounding context and the explainer's prior
      knowledge. In this article, we suggest that generating an explanation involves
      two operations: one that homes in on an interpretation of the question, and a
      second one that locates an answer. We review empirical work that supports this
      account, consider the implications of these contrastive processes, and identify
      areas for future study.

PMID- 28762031
TI  - Polymers for Traveling Wave Ion Mobility Spectrometry Calibration.
AB  - One of the main issues when using traveling wave ion mobility spectrometry
      (TWIMS) for the determination of collisional cross-section (CCS) concerns the
      need for a robust calibration procedure built from referent ions of known CCS.
      Here, we implement synthetic polymer ions as CCS calibrants in positive ion mode.
      Based on their intrinsic polydispersities, polymers offer in a single sample the
      opportunity to generate, upon electrospray ionization, numerous ions covering a
      broad mass range and a large CCS window for different charge states at a time. In
      addition, the key advantage of polymer ions as CCS calibrants lies in the
      robustness of their gas-phase structure with respect to the instrumental
      conditions, making them less prone to collisional-induced unfolding (CIU) than
      protein ions. In this paper, we present a CCS calibration procedure using sodium
      cationized polylactide and polyethylene glycol, PLA and PEG, as calibrants with
      reference CCS determined on a home-made drift tube. Our calibration procedure is
      further validated by testing the polymer calibration to determine CCS of numerous
      different ions for which CCS are reported in the literature. Graphical Abstract
      ?.

PMID- 28762032
TI  - [Surgical positioning techniques in urology : Tips and tricks].
AB  - Correct positioning of patients during preoperative preparations is essential for
      success of the intervention to avoid any positioning trauma and to provide the
      best access to the targeted structures. The appropriate positioning (and optimal
      performance) means that complications are avoided and also makes an essential
      contribution to the smooth course of the surgical intervention. A correct
      position is essential particularly in urology because the organs assigned to the
      discipline of urology are anatomically mostly difficult to reach. A further
      important function of the correct positioning technique is the avoidance of
      injuries to the patient. This article summarizes the most common positioning
      techniques in urological interventions with special emphasis on the explanation
      of practical advice, helpful tips and possible complications that can enable even
      junior surgeons to correctly perform the appropriate positioning technique.

PMID- 28762033
TI  - Inducible somatic embryogenesis in Theobroma cacao achieved using the DEX
      activatable transcription factor-glucocorticoid receptor fusion.
AB  - OBJECTIVES: To carry out mass propagation of superior plants to improve
      agricultural and silvicultural production though advancements in plant cell
      totipotency, or the ability of differentiated somatic plant cells to regenerate
      an entire plant. RESULTS: The first demonstration of a titratable control over
      somatic embryo formation in a commercially relevant plant, Theobroma cacao
      (Chocolate tree), was achieved using a dexamethasone activatable chimeric
      transcription factor. This four-fold enhancement in embryo production rate
      utilized a glucocorticoid receptor fused to an embryogenic transcription factor
      LEAFY COTYLEDON 2. Where previous T. cacao somatic embryogenesis has been
      restricted to dissected flower parts, this construct confers an unprecedented
      embryogenic potential to leaves. CONCLUSIONS: Activatable chimeric transcription
      factors provide a means for elucidating the regulatory cascade associated with
      plant somatic embryogenesis towards improving its use for somatic regeneration of
      transgenics and plant propagation.

PMID- 28762034
TI  - Transcriptome profiling analysis of differentially expressed mRNAs and lncRNAs in
      HepG2 cells treated with peptide 9R-P201.
AB  - OBJECTIVE: To characterize the transcriptome profile of hepatocellular carcinoma
      (HCC) HepG2 cells treated with peptide 9R-P201 for further functional
      verification and HCC drug development. RESULTS: 1557 mRNAs (1125 upregulated and
      432 downregulated) and 881 lncRNAs (640 upregulated and 241 downregulated) with
      significant differential expression were identified using RNA-seq. The qRT-PCR
      results showed that the differential expression of several mRNAs and lncRNAs
      coincided with the RNA-seq results. Differentially expressed mRNAs and lncRNAs
      presented a significant difference in genomic characteristics but no preference
      under 9R-P201 treatment compared with control. The GO and KEGG functional
      enrichment analyses showed that differentially expressed mRNAs and lncRNAs
      remarkably enriched in cancer-related biological processes and signaling
      pathways. Finally, we screened out 33 TFs, 273 lncRNAs and 94 target genes with
      high degree interaction which were remarkably associated with the tumorigenesis
      and progression of cancers using betweenness centrality analysis. CONCLUSION:
      These findings offer novel insights into the mechanism of 9R-P201 in HepG2 cells
      and provide new opportunities for the future 9R-P201-based drug development and
      the treatment of hepatocellular carcinoma.

PMID- 28762035
TI  - Characterization of a novel nitrilase, BGC4, from Paraburkholderia graminis
      showing wide-spectrum substrate specificity, a potential versatile biocatalyst
      for the degradation of nitriles.
AB  - OBJECTIVE: To investigate the biodegradation of nitriles via the nitrilase
      mediated pathway. RESULTS: A novel nitrilase, BGC4, was identified from
      proteobacteria Paraburkholderia graminis CD41M and its potential for use in
      biodegradation of toxic nitriles in industrial effluents was studied. BGC4 was
      overexpressed in Escherichia coli BL21 (DE3), the recombinant protein was
      purified and its enzymatic properties analysed. Maximum activity of BGC4
      nitrilase was at 30  degrees C and pH 7.6. BGC4 has a broad substrate activity
      towards aliphatic, heterocyclic, and aromatic nitriles, as well as
      arylacetonitriles. Iminodiacetonitrile, an aliphatic nitrile, was the optimal
      substrate but comparable activities were also observed with phenylacetonitrile
      and indole-3-acetonitrile. BGC4-expressing cells degraded industrial nitriles,
      such as acrylonitrile, adiponitrile, benzonitrile, mandelonitrile, and 3
      cyanopyridine, showing good tolerance and conversion rates. CONCLUSION: BGC4
      nitrilase has wide-spectrum substrate specificity and is suitable for efficient
      biodegradation of toxic nitriles.

PMID- 28762036
TI  - The Astonishing Population Averted by China's Birth Restrictions: Estimates,
      Nightmares, and Reprogrammed Ambitions.
AB  - China launched an unprecedented program to control its population in 1971.
      Experts have dismissed the official estimate of 400 million births averted by
      this program as greatly exaggerated yet neglect to provide their own estimates.
      Counterfactual projections based on fertility declines in other countries suggest
      that China's program-averted population numbered 360-520 million as of 2015. The
      low end of this range is based on Vietnam-China's best national comparator, with
      a two-child program of its own-and the high end is based on a 16-country
      comparator selected, ironically, by critics of the official estimate. The latter
      comparator further implies that China's one-child program itself averted a
      population of 400 million by 2015, three-quarters of the total averted
      population. All such estimates are projected to double by 2060, due mostly to
      counterfactual population momentum. These and other findings presented herein
      affirm the astonishing impact of China's draconian policy choices and challenge
      the current consensus that rapid socioeconomic progress drove China's fertility
      well below two children per family. International comparisons of fertility and
      income suggest instead that China's very low fertility arrived two or three
      decades too soon. If China had not harshly enforced a norm of 1.5-children during
      the last quarter century, most mothers would have had two children, one-half
      birth higher than observed.

PMID- 28762037
TI  - Genetic polymorphism of growth differentiation factor 9 (GDF9) gene related to
      fecundity in two Egyptian sheep breeds.
AB  - PURPOSE: This study explores polymorphisms in the growth differentiation factor 9
      (GDF9) gene (exon 1) with respect to fertility in Egyptian sheep. METHODS: Blood
      samples were collected, and genomic DNA was extracted from 24 Saidi and 13 Ossimi
      ewes. A 710 bp portion of the GDF9 gene, was amplified using specific primers,
      and the sequence was analyzed to clarify the phylogenetic relationship of
      Egyptian breed sheep. In addition, the PCR-RFLP method using Pst1 or Msp1
      restriction enzymes was used to mask polymorphisms of partial exon 1 of GDF9 gene
      to establish molecular markers for twinning. RESULTS: The lambing rate percentage
      and litter size showed significant difference between ewes, which produce single
      and twin lamb for each breed individually, whereas the coefficient of variation
      of the Saidi breed is greater than that of the Ossimi breed. The results
      suggested that the GDF9 gene shared a similarity in sequence compared to six
      accession numbers of Ovis aries found in GenBank. Molecular phylogenetic analyses
      were performed based on nucleotide sequences in order to examine the position of
      the Egyptian breeds among many other sheep breeds. The results indicate that
      accession number AF078545 of O. aries is closely related with Saidi and Ossimi
      ewes that produce single or twin lamb using the unweighted pair group method with
      arithmetic mean (UPGMA) analysis. Results showed that Msp1 enzyme digestion
      revealed polymorphic restriction pattern consisting of one band with 710 bp for
      ewes producing single lamb and two bands with 710 and 600 bp for ewes producing
      twin lamb in Saidi sheep breed. CONCLUSION: Sequence analysis and diversity of
      polymorphisms in the GDF9 gene (exon 1) have a novel base substitution (A-T) for
      detection of FecG mutations that serve as a molecular marker for twinning.

PMID- 28762038
TI  - Considerations in T Cell Therapy Product Development for B Cell Leukemia and
      Lymphoma Immunotherapy.
AB  - Based on laboratory and clinical research findings and investments in
      immunotherapy by many institutions in academia, government-funded laboratories,
      and industry, there is tremendous and deserved excitement in the field of cell
      and gene therapy. In particular, understanding of immune-mediated control of
      cancer has created opportunities to develop new forms of therapies based on
      engineered T cells. Unlike conventional drugs or biologics, the source material
      for these new therapies is collected from the patient or donor. The next step is
      commonly either enrichment to deplete unwanted cells, or methods to positively
      select T cells prior to polyclonal expansion or antigen-specific expansion. As
      the first generation of engineered T cell therapies have demonstrated proof of
      concept, the next stages of development will require the integration of automated
      technologies to enable more consistent manufacturing and the ability to produce
      therapies for more patients.

PMID- 28762040
TI  - Case update on cranial osteopetrosis: which is the role of the neurosurgeon?
AB  - PURPOSE: Osteopetrosis (OP) is a rare skeletal disease, which can affect the
      skull base and calvaria. A multidisciplinary approach is mandatory and patient
      may need neurosurgical care. Few observations have been published, and optimal
      management of OP is not established yet. METHOD: We report a case of an infant
      with OP diagnosed at 5 months, who presented signs of intracranial hypertension
      associated with unilateral blindness. Bone marrow allograft was performed at 6
      months of age. At neurosurgical first examination at 11 months, the child was
      hypotonic, with severe amblyopia; features of bicoronal synostosis were
      appreciated, with tense anterior fontanel bulging indicating synostotic
      oxycephaly. Head circumference had decreased from +3 SD to +1SD. Cerebral CT scan
      showed reduction of intracranial volume, inward thickening of the calvaria,
      bilateral stenosis of optic canal, ventricular dilatation, enlarged arachnoid
      spaces, and tonsillar herniation. We performed cranial vault expansion with
      frontal advancement and bi parietal decompression, thinning of the inner table,
      unroofing of the left orbit and optic canal in order to obtain optic nerve
      decompression. RESULTS: Postoperative course was uneventful, and the patient was
      discharged on day 8. Vision was unchanged but rapid improvement of axial tonus
      was noted. The CT scan showed satisfactory calvarial expansion with regression of
      tonsillar herniation. CONCLUSIONS: Neurosurgical evaluation and care are
      necessary in the context of a multidisciplinary approach to the patient affected
      by osteopetrosis. Cranial vault remodeling and expansion should be considered in
      patients with sign of intracranial hypertension. Timing of optic canal
      decompression is to be defined.

PMID- 28762039
TI  - Hypothalamic hamartoma presenting with infantile spasms.
AB  - BACKGROUND: Hypothalamic hamartomas (HH) generally present with gelastic
      seizures. It is very unusual for a pediatric patient with HH to present with
      infantile spasms (IS). CASE PRESENTATION: Here we present a 6-month-old boy
      diagnosed with IS whose brain magnetic resonance imaging (MRI) showed an 18 * 18
      * 16 mm mass in the hypothalamus. His seizures did not respond to antiepileptic
      treatment with vigabatrin and valproic acid. He had disconnective surgery for HH.
      Immediately postoperatively, his seizures subsided and he has now been seizure
      free for 2 years. CONCLUSION: Although hypothalamic hamartomas generally present
      with gelastic seizures, they should also be considered in the differential
      diagnosis of infantile spasms.

PMID- 28762041
TI  - Neuroinfluenza: evaluation of seasonal influenza associated severe neurological
      complications in children (a multicenter study).
AB  - PURPOSE: Although influenza primarily affects the respiratory system, in some
      cases, it can cause severe neurological complications. Younger children are
      especially at risk. Pediatric literature is limited on the diagnosis, treatment,
      and prognosis of influenza-related neurological complications. The aim of the
      study was to evaluate children who suffered severe neurological manifestation as
      a result of seasonal influenza infection. METHODS: The medical records of 14
      patients from six hospitals in different regions of the country were evaluated.
      All of the children had a severe neurological manifestations related to
      laboratory-confirmed influenza infection. RESULTS: Median age of the patients was
      59 months (6 months-15.5 years) and nine (64.3%) were male. Only 4 (28.6%) of the
      14 patients had a comorbid disease. Two patients were admitted to hospital with
      influenza-related late complications, and the remainder had acute complication.
      The most frequent complaints at admission were fever, altered mental status,
      vomiting, and seizure, respectively. Cerebrospinal fluid (CSF) analysis was
      performed in 11 cases, and pleocytosis was found in only two cases.
      Neuroradiological imaging was performed in 13 patients. The most frequent
      affected regions of nervous system were as follows: cerebellum, brainstem,
      thalamus, basal ganglions, periventricular white matter, and spinal cords. Nine
      (64.3%) patients suffered epileptic seizures. Two patients had focal seizure, and
      the rest had generalized seizures. Two patients developed status epilepticus.
      Most frequent diagnoses of patients were encephalopathy (n = 4), encephalitis (n
      = 3), and meningitis (n = 3), respectively. The rate of recovery without sequelae
      from was found to be 50%. At discharge, three (21.4%) patients had mild symptoms,
      another three (21.4%) had severe neurological sequelae. One (7.1%) patient died.
      The clinical findings were more severe and outcome was worse in patients <5 years
      old than patients >5 years old and in patients with comorbid disease than
      previously healthy group. CONCLUSION: Seasonal influenza infection may cause
      severe neurological complications, especially in children. Healthy children are
      also at risk such as patients with comorbid conditions. All children who are
      admitted with neurological findings, especially during the influenza season,
      should be evaluated for influenza-related neurological complications even if
      their respiratory complaints are mild or nonexistent.

PMID- 28762042
TI  - Spina bifida: a prospective study from a single neurosurgical center based on the
      National Hospital in Niamey (Niger).

PMID- 28762043
TI  - Customised in vitro model to detect human metabolism-dependent idiosyncratic drug
      induced liver injury.
AB  - Drug-induced liver injury (DILI) has a considerable impact on human health and is
      a major challenge in drug safety assessments. DILI is a frequent cause of liver
      injury and a leading reason for post-approval drug regulatory actions.
      Considerable variations in the expression levels of both cytochrome P450 (CYP)
      and conjugating enzymes have been described in humans, which could be responsible
      for increased susceptibility to DILI in some individuals. We herein explored the
      feasibility of the combined use of HepG2 cells co-transduced with multiple
      adenoviruses that encode drug-metabolising enzymes, and a high-content screening
      assay to evaluate metabolism-dependent drug toxicity and to identify metabolic
      phenotypes with increased susceptibility to DILI. To this end, HepG2 cells with
      different expression levels of specific drug-metabolism enzymes (CYP1A2, CYP2B6,
      CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, GSTM1 and UGT2B7) were exposed to nine
      drugs with reported hepatotoxicity. A panel of pre-lethal mechanistic parameters
      (mitochondrial superoxide production, mitochondrial membrane potential, ROS
      production, intracellular calcium concentration, apoptotic nuclei) was used.
      Significant differences were observed according to the level of expression and/or
      the combination of several drug-metabolism enzymes in the cells created ad hoc
      according to the enzymes implicated in drug toxicity. Additionally, the main
      mechanisms implicated in the toxicity of the compounds were also determined
      showing also differences between the different types of cells employed. This
      screening tool allowed to mimic the variability in drug metabolism in the
      population and showed a highly efficient system for predicting human DILI,
      identifying the metabolic phenotypes associated with increased DILI risk, and
      indicating the mechanisms implicated in their toxicity.

PMID- 28762044
TI  - Effect of practicing yoga on cervical vestibular evoked myogenic potential.
AB  - The present study attempted to determine the effect of practicing yoga on
      functioning of sacculo-collic pathway using cervical vestibular evoked myogenic
      potential (cVEMP). cVEMP was recorded from 40 participants (20 who practice yoga
      regularly and 20 who do not practice yoga regularly). The differences in
      amplitude of P1, N1, P1-N1 complex, asymmetry ratio and latencies of P1 and N1 of
      cVEMP were compared between both the groups. The results of the study showed that
      there was a significant increase (p < 0.05) in the amplitude of P1, N1 and P1-N1
      complex and a significant reduction in latency (p < 0.05) for experimental group.
      The asymmetry ratio in individuals who practice yoga was significantly lower
      (Mean = 6.73) compared to the control group (Mean = 19.13). Multivariate
      regression analyses suggested that the number of years of yoga practice
      significantly predicted the amplitude of P1-N1 complex (beta = 0.70, p < 0.01)
      and amplitude ratio (beta = 0.72, p < 0.01). Thus, practicing yoga improves
      postural control and strengthens the muscles and vestibular system leading to
      enhanced cVEMP responses. The plastic changes in the vestibular system and
      increased muscular strength because of constant practicing of yoga could have led
      to changes in cVEMP responses. However, further studies on a larger group of
      individuals are essential for better clinical applicability of the results.

PMID- 28762045
TI  - Hybrid cochlear implantation: quality of life, quality of hearing, and working
      performance compared to patients with conventional unilateral or bilateral
      cochlear implantation.
AB  - The objective of the present study is to evaluate the effect of hybrid cochlear
      implantation (hCI) on quality of life (QoL), quality of hearing (QoH), and
      working performance in adult patients, and to compare the long-term results of
      patients with hCI to those of patients with conventional unilateral cochlear
      implantation (CI), bilateral CI, and single-sided deafness (SSD) with CI. Sound
      localization accuracy and speech-in-noise test were also compared between these
      groups. Eight patients with high-frequency sensorineural hearing loss of unknown
      etiology were selected in the study. Patients with hCI had better long-term
      speech perception in noise than uni- or bilateral CI patients, but the difference
      was not statistically significant. The sound localization accuracy was equal in
      the hCI, bilateral CI, and SSD patients. QoH was statistically significantly
      better in bilateral CI patients than in the others. In hCI patients, residual
      hearing was preserved in all patients after the surgery. During the 3.6-year
      follow-up, the mean hearing threshold at 125-500 Hz decreased on average by 15 dB
      HL in the implanted ear. QoL and working performance improved significantly in
      all CI patients. Hearing outcomes with hCI are comparable to the results of
      bilateral CI or CI with SSD, but hearing in noise and sound localization are
      statistically significantly better than with unilateral CI. Interestingly, the
      impact of CI on QoL, QoH, and working performance was similar in all groups.

PMID- 28762046
TI  - Effects and mechanisms of meta-sodium silicate amendments on lead uptake and
      accumulation by rice.
AB  - The objectives of this research were to study the effects of Na2SiO3 application
      on the uptake, translocation, and accumulation of Pb in rice and to investigate
      the mechanisms of Pb immobilization by Na2SiO3 in paddy rice soils and rice
      plants. Pot experiments were conducted using a Cd-Pb-Zn-polluted soil and Oryza
      sativa L. ssp. indica cv. Donglian 5. L3-edge X-ray absorption spectroscopy was
      used to identify Pb species in soils and roots. The results showed that the
      application of Na2SiO3 increased soil pH and available soil Si but decreased DTPA
      extractable Pb in the soil. High dose of Na2SiO3 (12.5 g/kg) reduced the Pb level
      in brown rice as it inhibited Pb transfer from soil to rice grains, especially Pb
      transfer from the root to the stem. The Pb X-ray absorption near-edge
      spectroscopic analysis revealed that application of high dose of Na2SiO3
      increased Pb-ferrihydrite and PbSiO3 precipitates in the soil and in the root
      while it reduced Pb-humic acids (Pb-HAs) in the soil and Pb-pectin in the root.
      The decrease in Pb availability in the soil can be partly attributed to increase
      the precipitation of PbSiO3 and the association of Pb2+ with Fe oxides in the
      soil. The inhibition of the root-to-stem translocation of Pb was partially due to
      the precipitation of PbSiO3 on the root surfaces or inside the roots.

PMID- 28762047
TI  - Pyrite oxidation under simulated acid rain weathering conditions.
AB  - We investigated the electrochemical corrosion behavior of pyrite in simulated
      acid rain with different acidities and at different temperatures. The cyclic
      voltammetry, polarization curve, and electrochemical impedance spectroscopy
      results showed that pyrite has the same electrochemical interaction mechanism
      under different simulated acid rain conditions, regardless of acidity or
      environmental temperature. Either stronger acid rain acidity or higher
      environmental temperature can accelerate pyrite corrosion. Compared with acid
      rain having a pH of 5.6 at 25  degrees C, the prompt efficiency of pyrite
      weathering reached 104.29% as the acid rain pH decreased to 3.6, and it reached
      125.31% as environmental temperature increased to 45  degrees C. Increasing
      acidity dramatically decreases the charge transfer resistance, and increasing
      temperature dramatically decreases the passivation film resistance, when other
      conditions are held constant. Acid rain always causes lower acidity mine
      drainage, and stronger acidity or high environmental temperatures cause serious
      acid drainage. The natural parameters of latitude, elevation, and season have
      considerable influence on pyrite weathering, because temperature is an important
      influencing factor. These experimental results are of direct significance for the
      assessment and management of sulfide mineral acid drainage in regions receiving
      acid rain.

PMID- 28762048
TI  - Pharmaceuticals and personal care products (PPCPs) in Arctic environments:
      indicator contaminants for assessing local and remote anthropogenic sources in a
      pristine ecosystem in change.
AB  - A first review on occurrence and distribution of pharmaceuticals and personal
      care products (PPCPs) is presented. The literature survey conducted here was
      initiated by the current Assessment of the Arctic Monitoring and Assessment
      Programme (AMAP). This first review on the occurrence and environmental profile
      of PPCPs in the Arctic identified the presence of 110 related substances in the
      Arctic environment based on the reports from scientific publications, national
      and regional assessments and surveys, as well as academic research studies (i.e.,
      PhD theses). PPCP residues were reported in virtually all environmental
      compartments from coastal seawater to high trophic level biota. For Arctic
      environments, domestic and municipal wastes as well as sewage are identified as
      primary release sources. However, the absence of modern waste water treatment
      plants (WWTPs), even in larger settlements in the Arctic, is resulting in
      relatively high release rates for selected PPCPs into the receiving Arctic
      (mainly) aquatic environment. Pharmaceuticals are designed with specific
      biochemical functions as a part of an integrated therapeutically procedure. This
      biochemical effect may cause unwanted environmental toxicological effects on non
      target organisms when the compound is released into the environment. In the
      Arctic environments, pharmaceutical residues are released into low to very low
      ambient temperatures mainly into aqueous environments. Low biodegradability and,
      thus, prolonged residence time must be expected for the majority of the
      pharmaceuticals entering the aquatic system. The environmental toxicological
      consequence of the continuous PPCP release is, thus, expected to be different in
      the Arctic compared to the temperate regions of the globe. Exposure risks for
      Arctic human populations due to consumption of contaminated local fish and
      invertebrates or through exposure to resistant microbial communities cannot be
      excluded. However, the scientific results reported and summarized here, published
      in 23 relevant papers and reports (see Table S1 and following references), must
      still be considered as indication only. Comprehensive environmental studies on
      the fate, environmental toxicology, and distribution profiles of pharmaceuticals
      applied in high volumes and released into the Nordic environment under cold
      Northern climate conditions should be given high priority by national and
      international authorities.

PMID- 28762049
TI  - Biogenic synthesis of gold nanoparticles from Terminalia arjuna bark extract:
      assessment of safety aspects and neuroprotective potential via antioxidant,
      anticholinesterase, and antiamyloidogenic effects.
AB  - The development of neuroprotective drugs through eco-friendly production routes
      is a major challenge for current pharmacology. The present study was carried out
      to synthesize gold nanoparticles (AuNPs) through biogenic route using ethanolic
      bark extract of Terminalia arjuna, a plant of high interest in Asian traditional
      medicine, and to evaluate its neuroprotective effects. The synthesized AuNPs were
      characterized by UV-Vis spectroscopy, FTIR spectroscopy, XRD, FESEM, EDX, HRTEM,
      DLS, and zeta potential analyses. UV-Vis spectroscopy showed a characteristics
      SPR absorption band at 536 nm specific for AuNPs. XRD, TEM, and FESEM analyses
      revealed the formation of face-centered cubic crystalline, spherical and
      triangular shaped AuNPs, with size ranging between 20 and 50 nm. DLS and ZP
      analysis illustrated that the average size of AuNPs was 30 nm, which was found to
      be stable at 45 mv. The neuroprotective potential of AuNPs was evaluated by
      assessing its antioxidant, cholinesterase inhibitory, and antiamyloidogenic
      activities. AuNPs showed dose-dependant inhibition of acetylcholinesterase and
      butyrylcholinesterase with IC50 value of 4.25 +/- 0.02 and 5.05 +/- 0.02 MUg/ml,
      respectively. In vitro antioxidant assays illustrated that AuNPs exhibited the
      highest reducing power and DPPH radical scavenging activity. In addition, AuNPs
      also efficiently suppressed the fibrillation of Abeta and destabilized the
      preformed mature fibrils. Results of toxicity studies in PBMC and adult zebra
      fish illustrated that AuNPs are non-toxic and biocompatible. Overall, our results
      highlighted the AuNPs promising potential in terms of antioxidant,
      anticholinesterase, antiamyloidogenic effects, and non-lethality allowing us to
      propose these nanomaterials as a suitable candidate for the development of drugs
      helpful in the treatment of neurodegenerative disorders like Alzheimer's disease.
      Graphical abstract ?.

PMID- 28762050
TI  - [Research on the skin microbiome : Fascinating and challenging].

PMID- 28762051
TI  - Can premium differentiation counteract adverse selection in the Dutch
      supplementary health insurance? A simulation study.
AB  - Most health insurers in the Netherlands apply community-rating and open enrolment
      for supplementary health insurance, although it is offered at a free market.
      Theoretically, this should result in adverse selection. There are four
      indications that adverse selection indeed has started to occur on the Dutch
      supplementary insurance market. The goal of this paper is to analyze whether
      premium differentiation would be able to counteract adverse selection. We do this
      by simulating the uptake and premium development of supplementary insurance over
      25 years using data on healthcare expenses and background characteristics from
      110,261 insured. For the simulation of adverse selection, it is assumed that only
      insured for whom supplementary insurance is expected not to be beneficial will
      consider opting out of the insurance. Therefore, we calculate for each insured
      the financial profitability (by making assumptions about the consumer's expected
      claims and the premium set by the insurer), the individual's risk attitude and
      the probability to opt out or opt in. The simulation results show that adverse
      selection might result in a substantial decline in insurance uptake.
      Additionally, the simulations show that if insurers were to differentiate their
      premium to 28 age and gender groups, adverse selection could be modestly
      counteracted. Finally, this paper shows that if insurers would apply highly
      refined risk-rating, adverse selection for this type of supplementary insurance
      could be counteracted completely.

PMID- 28762053
TI  - Erratum to: Dose-related effect of statins in patients with endovascular coiling
      or microsurgical clipping for aneurysmal subarachnoid hemorrhage: updated study
      level meta-analysis.

PMID- 28762052
TI  - In Vitro Mechanical Property Evaluation of Chitosan-Based Hydrogels Intended for
      Vascular Graft Development.
AB  - Vascular grafts made of synthetic polymers perform poorly in cardiac and
      peripheral bypass applications. In these applications, chitosan-based materials
      can be produced and shaped to provide a novel scaffold for vascular tissue
      engineering. The goal of this study was to evaluate in vitro the mechanical
      properties of a novel chitosan formulation to assess its potential for this
      scaffold. Two chitosan-based hydrogel tubes were produced by modulating chitosan
      concentration. Based on the standard ISO 7198:1998, the hydrogel tubes were
      characterized in vitro in terms of suture retention strength, tensile strength,
      compliance, and burst pressure. By increasing chitosan concentration, suture
      retention value increased to reach 1.1 N; average burst strength and elastic
      moduli also increased significantly. The compliance seemed to exhibit a low value
      for chitosan tubes of high concentration. By modulating chitosan concentration,
      we produced scaffolds with suitable mechanical properties to be implanted in vivo
      and withstand physiological blood pressures.

PMID- 28762054
TI  - Hemispheric differences in the processing of visual consequences of active vs.
      passive movements: a transcranial direct current stimulation study.
AB  - Perceiving the sensory consequences of one's own actions is essential to
      successfully interact with the environment. Previous studies compared self-
      (active) and externally generated (passive) movements to investigate the
      processing of voluntary action-outcomes. Increased temporal binding (intentional
      binding) as well as increased detection of delays between action and outcome have
      been observed for active compared to passive movements. Using transcranial direct
      stimulation (tDCS) it has been shown that left hemispheric anodal stimulation
      decreased the intentional binding effect. However, whether the left hemisphere
      contributes to delay detection performance between action and outcome is unknown.
      We investigated polarization-dependent effects of left and right frontoparietal
      tDCS on detecting temporal action-outcome discrepancies. We applied anodal and
      cathodal stimulation to frontal (F3/F4), parietal (CP3/CP4) and frontoparietal
      (F3/CP4) areas. After stimulation, participants were presented with visual
      feedback with various delays after a key press. They had to report whether they
      detected a delay between the key press and the feedback. In half of the trials
      the key press was self-initiated, in the other half it was externally generated.
      A main effect of electrode location indicated highest detection performance after
      frontal stimulation. Furthermore, we found that the advantage for active versus
      passive conditions was larger for left hemispheric anodal stimulation as compared
      to cathodal stimulation. Whereas the frontal cortex is related to delay detection
      performance in general, hemispheric differences seem to support the
      differentiation of self-initiated versus externally generated movement
      consequences.

PMID- 28762055
TI  - Gulf War illness (GWI) as a neuroimmune disease.
AB  - Gulf War illness (GWI) is a chronic disease characterized by the involvement of
      several organs, including the brain (Christova et al., Exp Brain Res doi:
      10.1007/s00221-017-5010-8 , 2017). In a previous study (Georgopoulos et al., J
      Neural Eng 4:349-355, 2015), we identified six protective alleles from Class II
      human leukocyte antigen (HLA) genes, and more recently, we investigated the brain
      correlates of this protection (James et al., EBioMedicine 13:72-79, 2016). Those
      and other studies (Israeli, Lupus, 21:190-194, 2012) suggested an involvement of
      the immune system in GWI. In a recent study (Engdahl et al., EBioMedicine doi:
      10.1016/j.ebiom.2016.08.030 , 2016), we showed that the brain pattern of
      synchronous neural interactions (SNI; Georgopoulos et al., J Neural Eng 4:349
      355, 2007) in GWI is distinctly different from that in healthy controls. Here we
      focused on the SNI itself, as a basic measure of neural communication
      (irrespective of specific connections) and compared it between GWI and seven
      other diseases that cover a broad spectrum of etiology and pathophysiology.
      Specifically, we sought to determine which, if any, of those diseases might
      resemble GWI SNI, overall and within the HLA protective domain, and thus gain
      further knowledge regarding the nature of GWI brain abnormality. We studied a
      total of 962 participants from a healthy control population (N = 583) and eight
      different diseases, including GWI (N = 40), schizophrenia (SZ; N = 21),
      Alzheimer's disease (AD; N = 66), posttraumatic stress disorder (PTSD; N = 159),
      major depressive disorder (MDD; N = 10), relapsing-remitting multiple sclerosis
      (RRMS; N = 43), Sjogren's syndrome (SS; N = 32), and rheumatoid arthritis (RA; N
      = 8). They all underwent a resting-state magnetoencephalographic (MEG) scan to
      calculate SNIs. Data were analyzed using analysis of covariance (ANCOVA) with
      disease as fixed factor, and sex and age as covariates. We found that GWI SNIs
      differed significantly from control SZ, AD, PTSD and MDD but not from RRMS, SS
      and RA. In addition, we compared GWI to RRMS, SS and RA with respect to SNIs of
      MEG sensor pairs that were related to the HLA alleles protective for GWI (James
      et al., EBioMedicine 13:72-79, 2016). We found that GWI SNIs did not differ
      significantly from any of these three diseases but they did so from control SZ,
      AD, PTSD and MDD. These findings indicate that (a) GWI brain synchronicity does
      not differ significantly from that of known immune-related diseases (RRMS, SS,
      RA), and (b) that this SNI similarity is present within the HLA-related SNIs. In
      contrast, GWI SNIs differed significantly from those of the other diseases. We
      conclude that altered brain communication in GWI likely reflects immune-related
      processes, as postulated previously (James et al., EBioMedicine 13:72-79, 2016).
      By extension, these findings also indicate that functional brain abnormalities in
      RRMS, SS and RA might be, in part, due to lack of protective HLA alleles as
      documented for GWI (Georgopoulos et al., EBioMedicine 3:79-85, 2015).

PMID- 28762056
TI  - Functional brain effects of hand disuse in patients with trapeziometacarpal joint
      osteoarthritis: executed and imagined movements.
AB  - The human trapeziometacarpal (TMC) joint has a crucial evolutionary importance as
      it permits rotation and opposition of the thumb to the other fingers. In chronic
      TMC joint osteoarthritis (i.e., rhizarthrosis), this motor ability, essential for
      pinching, grasping, and manipulating objects, may become difficult or impossible
      due to intolerable pain. Here, we assess whether patients with rhizarthrosis show
      signs of abnormal brain representation of hand movements. To this end, we studied
      35 patients with rhizarthrosis, affecting predominantly one of the two hands, and
      35 healthy subjects who underwent both behavioural and fMRI measures of brain
      activity during overtly executed or imagined thumb-to-finger-opposition
      movements. The patients with rhizarthrosis were slower than controls both in
      motor execution and imagination. In the patients, correlation between the motor
      execution and imagination times was preserved, even though such correlation was
      less strong than in normal controls. The fMRI measures showed reduced activation
      in the hand primary motor and dorsal premotor cortex for the patients only during
      explicit movements. This was true for both hands, yet more so for the most
      affected hand. No significant differences were seen for the motor imagery task.
      These results show that an orthopaedic disorder that reduces patients' motoric
      repertoire in the absence of any neurological impairment is sufficient to induce
      neurofunctional changes in the cortical representation of hand movements. The
      substantial preservation of motor imagery with its neural counterparts
      distinguishes the neurological patterns of rhizarthrosis from those of complete
      immobilization or amputation suggesting that motor imagery may be used to boost
      motor recovery in rhizarthrosis after surgical treatment.

PMID- 28762058
TI  - Advantages of laparoscopic common bile duct exploration in common bile duct
      stones.
AB  - OBJECTIVE: To compare the efficacy, safety, and surgical outcomes of laparoscopic
      common bile duct exploration, endoscopic retrograde cholangiopancreatography, and
      open common bile duct exploration for treatment of common bile duct stones.
      METHODS: In total, 210 patients were prospectively randomized into 3 groups:
      laparoscopic common bile duct exploration, endoscopic retrograde
      cholangiopancreatography, and open common bile duct exploration. The primary
      outcome measures were the common bile duct stone clearance rate and the
      complication rate. The secondary outcome measures were mortality, total costs,
      and length of hospital stay. RESULTS: The success rates in the laparoscopic
      common bile duct exploration group (97.14%, 68 out of 70) and open common bile
      duct exploration group (98.57%, 69/70) were significantly higher than that in the
      endoscopic retrograde cholangiopancreatography group (85.71%, 60/70, both p <
      0.05). The complication rates in the laparoscopic common bile duct exploration
      group (2.86%, 2/70) and open common bile duct exploration group (1.43%, 1/70)
      were significantly lower than that in the endoscopic retrograde
      cholangiopancreatography group (14.29%, 10/70, both p < 0.05). The success rate
      and complication rate were not significantly different between the laparoscopic
      common bile duct exploration group and open common bile duct exploration group
      (both p > 0.05). CONCLUSION: Laparoscopic common bile duct exploration provides
      an alternative therapeutic approach that was safer and more reliable, allowed for
      earlier recovery, and provided more cost-effective treatment of common bile duct
      stones.

PMID- 28762057
TI  - Catamenial pneumothorax since introduction of video-assisted thoracoscopic
      surgery : A systematic review.
AB  - BACKGROUND: Catamenial pneumothorax is an uncommon form of spontaneous
      pneumothorax in women. The exact epidemiology and pathogenesis remain elusive.
      Video-assisted thoracoscopic surgery is used for diagnostic and therapeutic
      purposes. OBJECTIVE: The aim of this review was to analyze the demographic
      features, intraoperative findings, treatment methods and outcome in catamenial
      pneumothorax patients. In addition, we assessed the relationship between
      catamenial pneumothorax and pelvic endometriosis. SEARCH STRATEGY: A PubMed
      search of medical literature, published from January 1993 (video-assisted
      thoracoscopic surgery first described in literature) to January 2015, using the
      keywords "catamenial pneumothorax" was performed. Our study complied with the
      preferred reporting of items for systematic reviews and meta-analysis principles.
      A total of 182 patients were included in the analysis, including 4 patients
      treated at our institution. SELECTION CRITERIA: The inclusion criteria of were
      recurrent (at least two) episodes of spontaneous pneumothorax in relation to
      onset of menses. DATA SELECTION AND ANALYSIS: Age at time of diagnosis, side
      affected, diagnosis of pulmonary endometriosis, intraoperative findings,
      histological confirmation of thoracic endometriosis, methods of treatment and
      outcome were recorded. MAIN RESULTS: In 2.9% of the patients no pathological
      lesions were found; however, 59.3% had endometrial implants and 57.0%
      diaphragmatic perforations. Pelvic endometriosis was reported in 39.5% patients.
      Patients with diagnosed pelvic endometriosis showed a significantly higher rate
      of endometrial implants and histologically confirmed endometriosis lesions than
      patients without pelvic endometriosis. In 26.9% of patients, recurrence was
      observed after treatment. CONCLUSION: Video-assisted thoracoscopic surgery
      provides good diagnostic and therapeutic results; however, 25% of patients
      experienced recurrence despite adequate treatment. A strong association exists
      between thoracic and pelvic endometriosis in catamenial pneumothorax patients.

PMID- 28762059
TI  - Moderate alcohol consumption and atherosclerosis : Meta-analysis of effects on
      lipids and inflammation.
AB  - OBJECTIVE: Alcohol consumption plays an important role in the risk of major
      cardiovascular diseases. We conducted a meta-analysis to summarize the
      association between moderate alcohol consumption and atherosclerosis. DESIGN: In
      this study four databases and reference lists of retrieved articles were searched
      to identify eligible studies. A meta-analysis was carried out of all
      interventional studies that assessed the effects of moderate alcohol consumption
      on concentrations of low density lipoprotein cholesterol, high density
      lipoprotein cholesterol, triglycerides, apolipoprotein A I, interleukin 6,
      plasminogen activator inhibitor 1, fibrinogen, and other biomarkers previously
      found to be associated with risk of atherosclerosis. RESULTS: A total of 31
      studies met the eligibility criteria. In response to moderate alcohol
      consumption, low density lipoprotein cholesterol decreased by 0.08 mmol/l (P =
      0.05), and high density lipoprotein cholesterol increased by 0.08 mmol/l (P <
      0.00001), whereas total cholesterol and triglyceride remained the same. Moreover,
      interleukin 6 decreased by 0.43 pg/ml (P = 0.03), whereas C-reactive protein and
      tumor necrosis factor a remained the same. Several hemostatic factors and
      adiponectin were modestly affected by alcohol consumption. CONCLUSION: Moderate
      alcohol consumption is causally related to lower risk of atherosclerosis through
      changes in lipid profiles and inflammation.

PMID- 28762060
TI  - A 2-year observational study on treatment targets in psoriatic arthritis patients
      treated with TNF inhibitors.
AB  - The aim of this study was to evaluate clinical remission and MDA in PsA patients
      who started TNF-inhibitors (TNFi) treatment with a 2-year follow-up. Concomitant
      therapies as well as comorbidities were assessed. Level of concordance of
      clinimetric indices and the potential predictive factors of remission/MDA were
      also evaluated. Clinical and laboratory evaluations were prospectively performed
      in PsA patients at baseline (T0) and after 22 (T22), 54 (T54), and 102 (T102)
      weeks of treatment. Disease activity and disability were assessed using DAS28,
      CPDAI, DAPSA, MDA, and HAQ-SpA. The Pearson correlation coefficient, univariate,
      and multivariate binary logistic regression were performed. A total of 221 PsA
      patients were included. Cardiovascular diseases and metabolic syndrome (MetS)
      resulted as the most frequent comorbidities. Clinical remission was achieved by
      over a half of the patients during the follow-up. Use of concomitant therapies,
      such as csDMARDs and steroids, was significantly reduced during the follow-up.
      Agreement among indices of treatment targets by k-statistics was excellent for
      CPDAI and DAPSA and good for MDA and DAS28 or DAPSA. Female sex and MetS resulted
      as negative prognostic factors of clinical remission and MDA at all the time
      points. TNFi are highly effective in achieving treatment targets in PsA patients.
      DAS28, CPDAI, DAPSA, and MDA show a good agreement. Female sex and MetS are
      associated with a lower probability to achieve remission in PsA patients.

PMID- 28762062
TI  - Sequential rituximab and omalizumab for the treatment of eosinophilic
      granulomatosis with polyangiitis (Churg-Strauss syndrome).
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg
      Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia
      and asthma. Clinical manifestations commonly seen in patients presenting with
      EGPA range from upper airway and lung involvement to neurological, cardiac,
      cutaneous, and renal manifestations. Treatment for severe presentations includes
      steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is
      associated with a good response in the treatment of vasculitis, but a variable
      response for the control of allergic symptoms. Here, we report a 16-year-old
      female patient with severe EGPA (gastrointestinal and cutaneous vasculitis,
      rhinitis and asthma) refractory to conventional treatment. She was treated with
      rituximab, which enabled rapid control of the vasculitis component of the
      disease, but there was no response to rhinitis and asthma. Additionally, she
      developed severe bronchospasm during rituximab infusion. Sequential rituximab and
      omalizumab were initiated, leading to remission of all manifestations of
      vasculitis, rhinitis, and asthma, in addition to bronchospasm related to
      rituximab infusion.

PMID- 28762061
TI  - Direct antiglobulin (Coombs) test in systemic lupus erythematosus patients.
AB  - The objective of the study is to study the positivity of Coombs test or direct
      antiglobulin test (DAT) in systemic lupus erythematosus (SLE) patients and its
      relationship with disease's clinical and serological profile. Retrospective study
      of 373 SLE patients seen at single Rheumatology Unit. Epidemiological data (age,
      gender, age at disease onset, auto declared ethnic background and tobacco use),
      clinical (malar rash, photosensitivity, oral ulcers, discoid lesions, serositis,
      glomerulonephritis, convulsions, psychosis, hemolytic anemia, leukopenia,
      lymphocytopenia and arthritis), and serological profile (anti ds DNA, anti Ro/SS
      A; anti La/SS-B, Anti RNP, Anti Sm, aCl (anticardiolipin) IgG, aCl Ig M, LA or
      lupus anticoagulant, rheumatoid factor and direct Coombs) were collected.
      Patients with a positive DAT were compared with the negatives. DAT was positive
      in 12.8% of patients and 54.3% of them had hemolytic anemia. In univariate
      analysis, a positive DAT was associated with hemolytic anemia (p < 0.0001),
      secondary antiphospholipid antibody syndrome (p = 0.02), anticardiolipin IgG (p <
      0.0001), lupus anticoagulant (p = 0.05), positive VDRL (p = 0.004), anti-RNP (p <
      0.0001), anti-Sm (p = 0.002), and anti-La (p = 0.02). Logistic regression
      revealed that hemolytic anemia, anti-RNP and anti-LA were independently
      associated with positive DAT. DAT was positive in 12.8% of SLE studied sample and
      54.3% of them had hemolytic anemia. This test was independently associated with
      hemolytic anemia, anti-RNP and anti-La antibodies.

PMID- 28762063
TI  - The first report on Listeria monocytogenes producing siderophores and responds
      positively to N-acyl homoserine lactone (AHL) molecules by enhanced biofilm
      formation.
AB  - Listeria monocytogenes are Gram-positive well-known emerging food-borne pathogens
      causing listeriosis in humans. In the present study, we have isolated biofilm
      forming Listeria sp. from utensils used by a local milk collection dairy society
      at Usgao Goa, which collects milk for Goa dairy. Through biochemical tests and
      16S rRNA sequence analysis, the bacterium was confirmed to be L. monocytogenes
      and designated as strain BN3, having GenBank accession number MF095110. We report
      for the first time Gram-positive L. monocytogenes strain BN3 producing iron
      chelating siderophores by chrome azurol S (CAS) agar test. Also, this is a first
      report which reveals that L. monocytogenes strain BN3 responds to N-hexanoyl
      homoserine lactone molecule (C6-HSL) by gradual increase in their biofilm-forming
      potential with a gradual increase in AHL (C6-HSL) concentration (250, 500 nM-1
      MUM) as compared to control revealed by crystal violet assay (CV) in microtiter
      plate. These results were further confirmed by scanning electron microscopy
      (SEM). A significant decrease in biofilm formation was observed when L.
      monocytogenes strain BN3 was treated with 10 ug/ml (R)-2-(2-hydroxynaphthalen-1
      yl)thiazolidine-4-carboxylic acid, but when 250 and 500 nM AHL molecules were
      added, biofilm formation in strain BN3 was found to be enhanced as compared to
      control even in the presence of antibacterial compound, (R)-2-(2
      hydroxynaphthalen-1-yl)thiazolidine-4-carboxylic acid. These results revealed
      that AHL molecules nullify the effect of antimicrobial compound and promote
      biofilm formation in L. monocytogenes strain BN3.

PMID- 28762064
TI  - Nomogram with potential clinical use to predict lymph node metastasis in
      endometrial cancer patients diagnosed incidentally by postoperative pathological
      assessment.
AB  - PURPOSE: To determine the clinical and pathological risk factors for lymph node
      metastasis (LNM) in patients with endometrial cancer and to create a nomogram to
      predict LNM in patients without surgical staging. METHODS: All patients with
      endometrial adenocarcinoma who were treated surgically at a university based
      gynecologic oncology clinic between January 2011 and December 2014 were
      recruited. Women with endometrial adenocarcinoma who were surgically staged
      including lymphadenectomy were included in the study. Data regarding clinical and
      pathological risk factors were recorded. The histopathologic slides from the
      staging surgeries were re-evaluated microscopically by a gynecologic pathologist
      for all parameters along with lymphovascular space invasion (LVSI). RESULTS: A
      total of 279 patients with endometrial cancer were analyzed. Among those, 31
      (11.1%) had lymph node metastasis. According to the univariate analyses, elevated
      CA 125 (>35 U/mL), LVSI, myometrial invasion >=50%, grade 3 disease, non
      endometrioid type, and cervical stromal involvement were significantly associated
      with LNM. The multivariate logistic regression analysis showed that LVSI, non
      endometrioid type, elevated CA 125, and cervical stromal involvement increased
      the risk of LNM. However, myometrial invasion and grade did not significantly
      affect the risk of LNM. A nomogram to predict LNM was constructed using these
      factors (concordance index 0.92). CONCLUSIONS: LVSI is the most important
      predictor for LNM. The present nomogram can be useful to decide if adjuvant
      therapy is required for patients who undergo simple hysterectomy for a benign
      etiology and incidentally diagnosed with endometrial cancer by pathological
      evaluation.

PMID- 28762065
TI  - LC-high resolution-MS/MS for identification of 69 metabolites of the new
      psychoactive substance 1-(4-ethylphenyl-)-N-[(2-methoxyphenyl)methyl] propane-2
      amine (4-EA-NBOMe) in rat urine and human liver S9 incubates and comparison of
      its screening power with further MS techniques.
AB  - 4-EA-NBOMe (N-(2-methoxybenzyl)-4-ethylamphetamine, 1-(4-ethylphenyl-)-N-[(2
      methoxyphenyl)methyl]propane-2-amine) is an amphetamine-derived new psychoactive
      substance (NPS) of the N-methoxybenzyl (NBOMe) group first seized by German
      custom authorities. In contrast to the phenethylamine NBOMes, studies on the
      pharmacological, toxicological, or metabolic properties are not yet published.
      The aims of the presented work were the use of LC-HR-MS/MS for identification of
      the phase I and II metabolites of 4-EA-NBOMe in rat urine and pooled human S9
      fraction (pS9) incubations, to compare metabolite formation in both models, to
      identify involved monooxygenases, and to elucidate its detectability in standard
      urine screening approaches (SUSAs) using GC-MS, LC-MSn, and LC-HR-MS/MS. 4-EA
      NBOMe was mainly metabolized by oxidation of the ethyl group to phenyl
      acetaldehyde, to benzoic acid, or to phenylacetic acid, by hydroxylation, and all
      combined with O-demethylation as well as by glucuronidation and sulfation of the
      main phase I metabolites in rats. With the exception of the oxidation to benzoic
      acid, all main metabolic reactions could be confirmed in the incubations with
      pS9. In total, 36 phase I and 33 phase II metabolites could be identified.
      Monooxygenase activity screenings revealed the general involvement of cytochrome
      P450 (CYP) 1A2, CYP2B6, and CYP3A4. An intake of 4-EA-NBOMe was detectable only
      via its metabolites by all SUSAs after low-dose administration. The main targets
      for both LC-MS screenings should be the phenylacetic acid derivative, the
      mandelic acid derivative both with and without additional O-demethylation, and,
      for GC-MS, the hydroxy metabolite after conjugate cleavage.

PMID- 28762066
TI  - Zeta potential: a case study of cationic, anionic, and neutral liposomes.
AB  - Zeta potential is often used to approximate a nanoparticle's surface charge,
      i.e., cationic, anionic, or neutral character, and has become a standard
      characterization technique to evaluate nanoparticle surfaces. While useful, zeta
      potential values provide only very general conclusions about surface charge
      character. Without a thorough understanding of the measurement parameters and
      limitations of the technique, these values can become meaningless. This case
      study attempts to explore the sensitivity of zeta potential measurement using
      specifically formulated cationic, anionic, and neutral liposomes. This study
      examines zeta potential dependence on pH and ionic strength, resolving power, and
      highlights the sensitivity of zeta potential to charged liposomes. Liposomes were
      prepared with cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and
      varying amounts of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2
      dioleoyl-sn-glycero-3-phospho-L-serine (DOPS). A strong linear relationship was
      noted between zeta potential values and the mole percentage of charged lipids
      within a liposome (e.g., cationic DOTAP or anionic DOPS). This finding could be
      used to formulate similar liposomes to a specific zeta potential, potentially of
      importance for systems sensitive to highly charged species. In addition, cationic
      and anionic liposomes were titrated with up to two mole percent of the neutral
      lipid 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene
      glycol)-2000] (lipid-PEG; LP). Very small amounts of the lipid-PEG (<0.2 mol%)
      were found to impart stability to the DOTAP- and DOPS-containing liposomes
      without significantly affecting other physicochemical properties of the
      formulation, providing a simple approach to making stable liposomes with cationic
      and anionic surface charge.

PMID- 28762068
TI  - Profiling of cardiolipins and their hydroperoxides in HepG2 cells by LC/MS.
AB  - Cardiolipin (CL) exists as crucial functional phospholipid in mitochondria. The
      oxidation of CL is concerned with mitochondrial dysfunction and various diseases.
      As main oxidation products, CL hydroperoxide (CL-OOH) plays a key role in
      intermediating oxidative reaction. Thus, direct analysis of CL-OOH is of great
      interest. In the present study, CL and CL-OOH profiles were analyzed in oxidized
      HepG2 cell lipid via HPLC-Orbitrap MS/MS. Furthermore, the contents of individual
      molecular species were compared between intact and AAPH-oxidized HepG2 cells. In
      total, 46 CL and 18 CL-OOH were identified from oxidized cell lipids, while 21 CL
      and 9 CL-OOH were detected in AAPH-treated cells. Most CL depleted significantly
      after AAPH inducement, with percentages varying from 8.3% (CL70:7) to 73.7%
      (CL72:4), depending on fatty acyl composition. While almost all the CL-OOH
      remarkably increased, among them 68:6-, 72:6-, and 72:7-OOHs were only detected
      in AAPH-treated cells. CL68:5- and CL68:4-OOH were the most abundant species,
      while CL70:5-OOH among all the species expressed the highest oxidation percentage
      of the corresponding CL. Our results showed practical separation, identification,
      and semi-quantitation of CL-OOH species, which could contribute to approaches to
      lipidomic analysis of CL and CL-OOH, as well as tracing biomarkers in
      mitochondrial oxidative stress diagnosis. Graphical abstract Illustration
      represents cardiolipin hydroperoxide structure and its content increasing in AAPH
      treated HepG2 cells by LC/MS analysis.

PMID- 28762069
TI  - Optimized experimental workflow for tandem mass spectrometry molecular networking
      in metabolomics.
AB  - New omics sciences generate massive amounts of data, requiring to be sorted,
      curated, and statistically analyzed by dedicated software. Data-dependent
      acquisition mode including inclusion and exclusion rules for tandem mass
      spectrometry is routinely used to perform such analyses. While acquisition
      parameters are well described for proteomics, no general rule is currently
      available to generate reliable metabolomic data for molecular networking analysis
      on the Global Natural Product Social Molecular Networking platform (GNPS).
      Following on from an exploration of key parameters influencing the quality of
      molecular networks, universal optimal acquisition conditions for metabolomic
      studies are suggested in the present paper. The benefit of data pre-clustering
      before initiating large datasets for GNPS analyses is also demonstrated.
      Moreover, an efficient workflow dedicated to Agilent Technologies instruments is
      described, making the dereplication process easier by unambiguously
      distinguishing isobaric isomers eluted at different retention times, annotating
      the molecular networks with chemical formulas, and giving access to semi
      quantitative data. This specific workflow foreshadows future developments of the
      GNPS platform.

PMID- 28762070
TI  - Systematic review: probiotics for functional constipation in children.
AB  - : We updated our 2010 systematic review on the efficacy of probiotics in the
      treatment of constipation in children. The MEDLINE, EMBASE, and Cochrane Library
      databases; clinical trial registries; and reference lists of included studies
      were searched to February 2017 for randomized controlled trials (RCTs) performed
      in children, with no language restriction. The primary outcome measure was
      treatment success, as defined by the investigators. We included seven RCTs with a
      total of 515 participants. Included trials were heterogeneous with respect to
      study population, probiotic strains, dosages, study duration, and follow-up.
      Pooled results of two RCTs showed no significant difference between the
      Lactobacillus rhamnosus casei Lcr35 and placebo groups with respect to treatment
      success. Other probiotics were studied in single trials only. There was no
      significant difference between the probiotic and control groups with respect to
      treatment success. While some probiotic strains showed some effects on defecation
      frequency, none of the probiotics had beneficial effects on frequency of fecal
      incontinence or frequency of abdominal pain. Adverse events were rare and not
      serious. CONCLUSION: Limited evidence does not support the use of any of
      currently evaluated probiotics in the treatment of functional constipation in
      children. What is Known: * Conventional treatment for functional constipation in
      children does not always provide satisfying improvement. * Probiotics have been
      suggested as potential treatment modalities for this condition. What is New: *
      Probiotics are ineffective for the management of functional constipation in
      children in terms of treatment success, frequency of fecal incontinence, and
      frequency of abdominal pain.

PMID- 28762071
TI  - An evaluation system for postgraduate pediatric residency programs: report of a 3
      year experience.
AB  - : The way a postgraduate medical training program is organized and the capacity
      of faculty members to function as tutors and to organize effective professional
      experiences are among the elements that affect the quality of training. An
      evaluation system designed to target these elements has been implemented within
      the framework of the Pediatric Residency Program of the University of Padua
      (Italy). The aim of this report is to describe some aspects of the experience
      gained in the first 3 years of implementation of the system (2013-2015). Data
      were collected using four validated questionnaires: the "Resident Assessment
      Questionnaire", the "Tutor-Assessment Questionnaire", the "Rotation-Assessment
      Questionnaire", and the "Resident Affairs Committee-Assessment Questionnaire".
      The response rate was 72% for the "Resident Assessment Questionnaires"; 78% for
      the "Tutor-/Rotation-Assessment Questionnaires" and 84% for the "Resident Affair
      Committee-Assessment Questionnaires". The scores collected were validated by
      psychometric tests. CONCLUSION: The high rates of completed questionnaires
      returned and the psychometric validation of the results collected indicate that
      the evaluation system reported herein can be effectively implemented. Efforts
      should be made to refine this system and, more importantly, to document its
      impact in improving the Pediatric Residency Program. What is known: * The
      elements that influence the quality of postgraduate training programs and the
      knowledge, performance, and competences of residents must be regularly assessed.
      * Comprehensive evaluation systems for postgraduate residency programs are not
      universally implemented also because quite often common guidelines and rules,
      well-equipped infrastructures, and financial resources are missing. What is new:
      * We show the feasibility of implementing an evaluation system that targets some
      of the key elements of a postgraduate medical training program in Italy, a
      European country in which the regulations governing training programs and,
      notably, the evaluation of residents are still being developed.

PMID- 28762072
TI  - Sweet taste liking is associated with subjective response to amphetamine in women
      but not men.
AB  - RATIONALE AND OBJECTIVE: Preference for sweet taste rewards has been linked to
      the propensity for drug use in both animals and humans. Here, we tested the
      association between sweet taste liking and sensitivity to amphetamine reward in
      healthy adults. We hypothesized that sweet likers would report greater euphoria
      and stimulation following D-amphetamine (20 mg) compared to sweet dislikers.
      METHODS: Men (n = 36) and women (n = 34) completed a sweet taste test in which
      they rated their liking of various concentrations of sucrose and filtered water
      (0.05, 0.10, 0.21, 0.42, and 0.83 M). Participants who preferred the highest
      concentration were classified as "sweet likers." All others were classified as
      "sweet dislikers." They then completed four sessions in which they received D
      amphetamine (20 mg) and placebo in alternating order, providing self-report
      measures of euphoria and stimulation on the Addiction Research Center Inventory
      (ARCI) at regular intervals. We conducted linear mixed effects models to examine
      relationships between sweet liking and drug-induced euphoria and stimulation.
      RESULTS: Sweet likers reported significantly greater amphetamine-induced euphoria
      than did sweet dislikers among women. By contrast, sweet liking was not
      associated with amphetamine response in men. No associations with stimulation
      were observed. CONCLUSION: The association between sweet preference and
      amphetamine response in women is consistent with animal studies linking sweet
      taste preference and drug reward and also fits with observations that individuals
      who use drugs show a preference for sweet tastes. Whether the sex difference is
      related to circulating hormones, or other variables, remains to be determined.

PMID- 28762073
TI  - Alterations in brain activation in response to prolonged morphine withdrawal
      induced behavioral inflexibility in rats.
AB  - RATIONALE: The inability to stop a repetitive maladaptive behavior is a main
      problem in addictive disorders. Neuroadaptations that are associated with
      behavioral inflexibility may be involved in compulsive drug use. OBJECTIVES: The
      aim of the present study was to investigate the pattern of behavioral
      inflexibility during morphine withdrawal and map brain activation that is linked
      to alterations in flexibility. METHODS: We first analyzed the effects of chronic
      morphine exposure on reversal learning after 2-week (short-term) and 6-week
      (prolonged) morphine withdrawal. We then compared the level of neuronal
      activation using cFos immunohistochemistry in 15 brain areas between rats that
      underwent morphine withdrawal and saline-control rats after a test of reversal
      learning. RESULTS: Only prolonged morphine withdrawal impaired reversal learning.
      Rats that exhibited impairments in reversal learning presented a significant
      decrease in cFos expression in the orbitofrontal cortex (OFC), including the
      medial, lateral, and ventral OFC. cFos expression significantly increased in the
      dorsomedial striatum and major subregions of the medial prefrontal cortex (mPFC)
      in the morphine group. Rats that underwent prolonged morphine withdrawal
      exhibited no significant changes in cFos expression in the dorsolateral striatum,
      nucleus accumbens, amygdala, paraventricular thalamic nucleus, or motor cortex.
      The rats that underwent short-term withdrawal did not present any changes in cFos
      expression in any of these brain regions. CONCLUSION: Altogether, these data
      suggest that alterations in the function of the frontal cortex and its striatal
      connections during the late morphine withdrawal phase may underlie the disruption
      of inhibitory control in opioid dependence.

PMID- 28762075
TI  - Incidence and 5-year survival rate for head and neck cancers in Grenada compared
      to the African American population over the period 1991-2010.
AB  - Very little data exist on the incidence and burden of cancer in the individual
      Caribbean countries. Some data are available for larger areas, reported under a
      bigger geographical region; Latin America and the Caribbean, but many of the
      individual countries are not included. One of the main reasons is a lack of
      official cancer registries. Data are usually collected from hospital records or
      private physician records, and since it is not in an official registry, these
      data are not always accessible for inclusion in databases such as SEER and
      GLOBOCAN. Grenada is one of the countries that currently does not have a
      registry. Our aim is to report on the incidence for head and neck cancer with
      subcategories; hypopharynx, oropharynx, oral cavity, salivary glands, and larynx
      from data collected by the sole ear nose and throat specialist over a 20-year
      period. The age adjusted incidence per 100,000 for these cancers, whether
      combined or individually, is lower than that of similar populations. The
      incidence in males is only slightly higher than those reported in some parts of
      Africa. In females, only Eastern Africa is reported to have a lower incidence
      than that found in our study. While the incidence of oral cancers is lower than
      that of African Americans, the survival rate is comparable. Socioeconomic status,
      lack of infrastructure, and advanced stage at diagnosis appear to be closely
      related to the survival rate. Incidence reports suggest that incidence of head
      and neck cancers in individuals of African descent is lower than other
      populations. It is therefore not surprising that the incidence in Grenada is
      relatively low, although the incidence may be underestimated.

PMID- 28762074
TI  - The oral microbiota in patients with pancreatic cancer, patients with IPMNs, and
      controls: a pilot study.
AB  - PURPOSE: Poor oral health appears to be a risk factor for pancreatic cancer,
      possibly implicating the oral microbiota. In this pilot study, we evaluated the
      characteristics of the oral microbiota in patients with pancreatic ductal
      adenocarcinoma (PDAC), intraductal papillary mucinous neoplasms (IPMN), and
      healthy controls. METHODS: Forty newly diagnosed PDAC patients, 39 IPMN patients,
      and 58 controls, excluding current smokers and users of antibiotics, provided
      saliva samples. Common oral bacterial species were comprehensively surveyed by
      sequencing of the 16S rRNA microbial genes. We obtained measures of diversity and
      the mean relative proportions of individual taxa. We explored the degree to which
      these measures differed according to respondent characteristics based on
      individual interviews. RESULTS: PDAC cases did not differ in diversity measures
      from either controls or IPMN cases. PDAC cases had higher mean relative
      proportions of Firmicutes and related taxa, while controls had higher mean
      relative proportions of Proteobacteria and related taxa. Results were generally
      similar when comparing PDAC to IPMN cases. Among IPMNs and controls combined,
      younger individuals had higher levels of several taxa within the Proteobacteria.
      The only other variable consistently related to mean relative proportions was
      mouthwash use, with taxa within Firmicutes more common among users. CONCLUSIONS:
      While there were no differences in diversity of the oral microbiota among these
      groups, there were differences in the mean relative proportions of some taxa.
      Characteristics of the oral microbiota are not associated with most measures of
      oral health.

PMID- 28762076
TI  - The accumulation of beta-aminobutyric acid is controlled by the plant's immune
      system.
AB  - MAIN CONCLUSION: Endogenous levels of beta-aminobutyric acid (BABA) increase
      after the molecular recognition of pathogen presence. BABA is accumulated
      differently during resistance or susceptibility to disease. The priming molecule
      beta-aminobutyric acid has been recently shown to be a natural product of plants,
      and this has provided significance to the previous discovery of a perception
      mechanism in Arabidopsis. BABA levels were found to increase after abiotic stress
      or infection with virulent pathogens, but the role of endogenous BABA in defence
      has remained to be established. To investigate the biological significance of
      endogenous BABA variations during plant-pathogen interactions, we investigated
      how infections with virulent, avirulent (AvrRpt2), and non-pathogenic (hrpA)
      strains of Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), as well as
      treatment with defence elicitors (Flg22 and AtPep2), affect the accumulation of
      BABA in Arabidopsis plants. We found that BABA levels increased more rapidly
      during resistance than susceptibility to Pst DC3000. In addition, BABA was
      accumulated during PAMP-triggered immunity (PTI) after infection with the non
      pathogenic Pst DC3000 hrpA mutant, or treatment with elicitors. Importantly,
      treatment with Flg22 induced BABA rise in Columbia-0 plants but not in
      Wassilewskija-0 plants, which naturally possess a non-functional flagellin
      receptor. These results indicate that BABA levels are controlled by the plant's
      immune system, thus advancing the understanding of the biological role of plant
      produced BABA.

PMID- 28762077
TI  - Length of Involuntary Hospitalization Related to the Referring Physician's
      Psychiatric Emergency Experience.
AB  - Although involuntary commitment (IC) is a serious intervention in psychiatry and
      must always be regarded as an emergency measure, the knowledge about influencing
      factors is limited. Aims were to test the hypothesis that duration of involuntary
      hospitalization and associated parameters differ for IC's mandated by physicians
      with or with less routine experience in psychiatric emergency situations.
      Duration of involuntary hospitalization and duration until day-passes of 508
      patients with IC at the University Hospital of Psychiatry Zurich were analyzed
      using a generalized linear model. Durations of involuntary hospitalization and
      time until day-passes were significantly shorter in patients referred by
      physicians with less routine experience in psychiatric emergency situations than
      compared to experienced physicians. Shorter hospitalizations following IC by less
      experienced physicians suggest that some IC's might be unnecessary. A specific
      training or restriction to physicians being capable of conducting IC could
      decrease the rate of IC.

PMID- 28762078
TI  - Depression and Its Correlates Among Brazilian Immigrants in Massachusetts, USA.
AB  - The goal of this paper is to assess the frequency of depression symptoms among
      Brazilian immigrants living in Massachusetts, the second largest Brazilian
      immigrant population in the United States, and to identify correlates of
      depression. A convenience sample of Brazilian immigrants aged 18 or older
      residing in Massachusetts was used. Data were collected from December 2013 to
      March 2014, in the Consulate General of Brazil in Boston and in three religious
      events, using a structure questionnaire and the Center for Epidemiological
      Studies Depression Scale (CES-D). Depression symptoms were observed in 35.3% of
      the respondents, with equal distribution by sex. Correlates of depression were
      low income, being single, poor English proficiency, and poor self-perception of
      health. These results suggest a need for community outreach, sensitization, and
      counseling, in Portuguese and adapted to the culture of Brazilian immigrants.

PMID- 28762079
TI  - Elevated serum ferritin is not specific for hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal, syndrome
      of excessive and ineffective activation of the immune system. The majority of the
      reported data on HLH is from pediatric patients and lacks specificity. This makes
      HLH diagnosis challenging especially in adults where HLH is triggered by many
      conditions and can resemble many disease entities. Elevated ferritin is one of
      the diagnostic criteria for HLH. We determined the conditions associated with
      elevated ferritin at our medical center to assess how specific ferritin is for
      predicting HLH. We retrospectively reviewed all ferritin results >10,000 MUg/L in
      pediatric and adult patients. The most common condition associated with elevated
      ferritin was hematologic malignancy in adults (25.7%) and HLH in pediatric
      patients (48.9%). HLH was diagnosed in 14.2% of adults and 48.9% of children with
      ferritin >10,000 ug/L. Hyperferritinemia occurs in a variety of conditions and is
      not specific for adult or pediatric HLH. Common causes of elevated ferritin
      should be considered before entertaining the possibility of HLH, especially in
      adult patients.

PMID- 28762080
TI  - D816 mutation of the KIT gene in core binding factor acute myeloid leukemia is
      associated with poorer prognosis than other KIT gene mutations.
AB  - The clinical impact of KIT mutations in core binding factor acute myeloid
      leukemia (CBF-AML) is still unclear. In the present study, we analyzed the
      prognostic significance of each KIT mutation (D816, N822K, and other mutations)
      in Japanese patients with CBF-AML. We retrospectively analyzed 136 cases of CBF
      AML that had gone into complete remission (CR). KIT mutations were found in 61
      (45%) of the patients with CBF-AML. D816, N822K, D816 and N822K, and other
      mutations of the KIT gene were detected in 29 cases (21%), 20 cases (15%), 7
      cases (5%), and 5 cases (4%), respectively. The rate of relapse-free survival
      (RFS) and overall survival (OS) in patients with D816 and with both D816 and
      N822K mutations was significantly lower than in patients with other or with no
      KIT mutations (RFS: p < 0.001, OS: p < 0.001). Moreover, stratified analysis of
      the chromosomal abnormalities t(8;21)(q22;q22) and inv(16)(p13.1q22),
      t(16;16)(p13.1;q22) showed that D816 mutation was associated with a significantly
      worse prognosis. In a further multivariate analysis of RFS and OS, D816 mutation
      was found to be an independent risk factor for significantly poorer prognosis. In
      the present study, we were able to establish that, of all KIT mutations, D816
      mutation alone is an unfavorable prognostic factor.

PMID- 28762081
TI  - Ibrutinib versus previous standard of care: an adjusted comparison in patients
      with relapsed/refractory chronic lymphocytic leukaemia.
AB  - This study explored the relative efficacy of ibrutinib versus previous standard
      of-care treatments in relapsed/refractory patients with chronic lymphocytic
      leukaemia (CLL), using multivariate regression modelling to adjust for baseline
      prognostic factors. Individual patient data were collected from an observational
      Stockholm cohort of consecutive patients (n = 144) diagnosed with CLL between
      2002 and 2013 who had received at least second-line treatment. Data were compared
      with results of the RESONATE clinical trial. A multivariate Cox proportional
      hazards regression model was used which estimated the hazard ratio (HR) of
      ibrutinib versus previous standard of care. The adjusted HR of ibrutinib versus
      the previous standard-of-care cohort was 0.15 (p < 0.0001) for progression-free
      survival (PFS) and 0.36 (p < 0.0001) for overall survival (OS). A similar
      difference was observed also when patients treated late in the period (2012-)
      were compared separately. Multivariate analysis showed that later line of
      therapy, male gender, older age and poor performance status were significant
      independent risk factors for worse PFS and OS. Our results suggest that PFS and
      OS with ibrutinib in the RESONATE study were significantly longer than with
      previous standard-of-care regimens used in second or later lines in routine
      healthcare. The approach used, which must be interpreted with caution, compares
      patient-level data from a clinical trial with outcomes observed in a daily
      clinical practice and may complement results from randomised trials or provide
      preliminary wider comparative information until phase 3 data exist.

PMID- 28762082
TI  - Hemophagocytic lymphohistiocytosis (HLH) secondary to Ehrlichia chaffeensis with
      bone marrow involvement.

PMID- 28762083
TI  - Blastic plasmacytoid dendritic cell neoplasm: a pathological illustration of two
      clinical cases.

PMID- 28762084
TI  - Anatomy and histology of the scrotal ligament in adults: inconsistency and
      variability of the gubernaculum testis.
AB  - PURPOSE: The anatomy of gubernaculum testis (GT) is often discussed; however, the
      postnatal anatomy of the GT or scrotal ligament (SL) is rarely described. Hence,
      we performed an anatomical and histological study to analyze histologically the
      structures between testis and scrotum. METHODS: We performed anatomical
      dissections on 25 human fresh cadavers' testes. Each testis was removed with its
      envelopes and macroscopically analyzed. Then samples were included for
      histological study. Finally, they were analyzed under microscope, looking for
      attachments between testis, epididymis and scrotal envelopes. RESULTS: The
      absence of proximal and distal attachment was found in 56.0% of cases. Looking at
      the proximal attachment of the SL, the main one found is the epididymal
      attachment (28.0%), whereas no cases of testis attachment was found. Distally,
      there are more variations with scrotal attachment (12%) and cremaster attachment
      (12.0%). We found a significant prevalence of multiple adherences in 16.0% of
      cases too. Finally, in 15 cases (57.7%) an attachment is present between testis
      and epididymis, as it is commonly described. CONCLUSIONS: In the majority of
      cases there is no attachment of the lower pole of the testis and epididymis and
      these structures remain free. So it seems that the SL disappears with aging.
      Moreover, there is not only one kind of ligamentous attachment, but a high
      variability of attachments at the lower pole of the testiculo-epididymal
      structure. When it exists, this structure is never a real ligament and it seems
      more appropriate to use the term "attachments".

PMID- 28762085
TI  - The third ventricle roof: an anatomical study using constructive interference in
      steady-state magnetic resonance imaging.
AB  - PURPOSE: The third ventricle roof in vivo has been infrequently explored. The aim
      of the present study was to delineate the neurovascular structures relevant to
      the third ventricle roof using magnetic resonance (MR) imaging. METHODS: A total
      of 78 patients were enrolled in the study. Following initial examinations with
      conventional MR sequences, the constructive interference in steady-state (CISS)
      sequence was performed in coronal sections on 67 patients and in sagittal
      sections on 11 patients. RESULTS: In the coronal sections, the fornices and
      internal cerebral veins were delineated in all 67 patients. The cross-sectional
      appearance and size of the fornices were variable, and the relationship between
      fornices presented as five different types. In 82% of patients, dominance of one
      relationship type was not found. The diameter of the internal cerebral veins
      (ICVs) was also variable, and the relationship between ICVs presented as four
      different types. In 70% of patients, dominance of one relationship type was not
      found. In 52% of patients, the lower layer of the third ventricle roof was
      identified as an inhomogeneous membranous structure. In the sagittal sections,
      the lower layer of the third ventricle roof was delineated as an inhomogeneous
      linear structure with variable slopes. CONCLUSIONS: The third ventricle roof
      appears highly variable in morphology. Visualization of the third ventricle roof
      using the CISS sequence may be useful for planning safe and effective surgical
      maneuvers around the region.

PMID- 28762086
TI  - Regional microstructural damage and patterns of eye movement impairment: a DTI
      and video-oculography study in neurodegenerative parkinsonian syndromes.
AB  - Characteristic alterations of eye movement control are a common feature of
      neurodegenerative parkinsonism, including Parkinson's disease (PD), progressive
      supranuclear palsy (PSP), and multiple system atrophy (MSA). Regional
      microstructural alterations as assessed by diffusion tensor imaging (DTI) have
      been reported in PD, PSP, and MSA. Therefore, we investigated the specific
      association between eye movement disturbances and microstructural impairment in
      these diseases. Video-oculographic recordings of smooth pursuit and visually
      guided reactive saccades as well as fractional anisotropy (FA) maps computed from
      whole-brain DTI data were analyzed for 36 PD, 30 PSP, 18 MSA patients, and 23
      matched healthy control subjects. In PSP, peak eye velocity was pathologically
      slowed compared to controls (p < 0.001) and correlated significantly with
      microstructural impairment in the midbrain (p < 0.001, corrected). Smooth pursuit
      eye movements were substantially disturbed in MSA mainly by characteristic 'catch
      up' saccades resulting in significantly reduced pursuit gain (p < 0.001,
      corrected), and the shape of saccadized pursuit in MSA was significantly
      correlated with FA reductions in the middle cerebral peduncle (p < 0.001, FDR
      corrected). The prevalence of saccadic intrusions as a measure for inhibitory
      control was significantly increased in PD compared with controls (p < 0.001), but
      was uncorrelated with FA in cortical and subcortical white matter. Eye movement
      disturbances in PSP and MSA-but not in PD-are associated with diagnosis-specific
      regional microstructural alterations in the white matter. The non-invasive
      quantified oculomotor function analysis can give clues to the underlying
      structural connectivity network pathology and underpins its role as a technical
      marker in PSP and MSA.

PMID- 28762088
TI  - Effects of test item disclosure on medical licensing examination.
AB  - In 2012, the National Health Personnel Licensing Examination Board of Korea
      decided to publicly disclose all test items and answers to satisfy the test
      takers' right to know and enhance the transparency of tests administered by the
      government. This study investigated the effects of item disclosure on the medical
      licensing examination (MLE), examining test taker performance, psychometric
      characteristics, and factors affecting pass rates. This paper analyzed examinee
      performance data (n = 20,455) from 41 medical schools who took the MLE before
      (2009-2011) and after (2012-2014) the item disclosure policy (5548 total items).
      Changes in passing rates, performance of examinee, difficulty and reliability of
      the test, and factors affecting pass rate of the medical licensing examination
      before and after item disclosure were analyzed. In order to identify changes
      caused by item disclosure in the effects of student and school variables on the
      passing rate of MLE, Binary Logistic Hierarchical Linear Model was used. There
      was no significant change in pass rates before and after item disclosure. There
      was a modest increase in the proportion of test takers in the high-scoring group,
      following item disclosure. Degree completion status, gender, age of applicants
      and school mean were significant factors affecting pass rates, regardless of item
      disclosure. There was no difference between passing rates before and after item
      disclosure with respect to student- and school-level variables. Despite potential
      concerns for changes in test and examinee characteristics, empirical findings
      indicate that there was no significant difference caused by implementing item
      disclosure.

PMID- 28762087
TI  - Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical
      Characteristics and Management in a Real-Life Setting: a French Retrospective
      Analysis (GFPC 02-14 Study).
AB  - BACKGROUND: Chromosomal translocations involving the anaplastic lymphoma kinase
      gene (ALK) are rare oncogenic events found in 3-5% of non-small-cell lung cancers
      (NSCLC). Limited data have been published on the management of these patients
      outside clinical trials. OBJECTIVE: To investigate the clinical characteristics
      and management of patients with NSCLC harboring ALK translocations (ALK+) in a
      real-life setting in France. METHODS: This multicenter, observational,
      retrospective study included all NSCLC patients harboring ALK translocations
      diagnosed in participating centers between January 2012 and December 2014.
      Patient data include clinical characteristics, disease management, and outcomes
      [progression-free survival (PFS) and overall survival (OS)]. RESULTS: The 31
      participating centers reported data on 132 patients, of whom 51% (n = 67) were
      male. The median age was 60.1 +/- 14.5 (standard deviation) years; 89% (n =
      106/119) had performance status 0/1 at diagnosis; 79% (n = 103/130) were non- or
      former smokers; 93% (n = 120/129) had adenocarcinomas and 74%(n = 97)/19%(n =
      25)/7%(n = 10) had disease stages IV/III/I-II at diagnosis, respectively; co
      mutations included EGFR (n = 2), BRAF (n  = 2), KRAS (n = 1), and HER2 (n = 1).
      Of the patients with stage IV NSCLC (n = 97), 96% received first-line treatment
      [75% chemotherapy-based, 21% ALK tyrosine kinase inhibitor (TKI)], with an
      associated response rate (RR), disease-control rate (DCR), and PFS of 42%, 64%,
      and 7.5 [95% confidence interval (CI) 5.9-9.5] months, respectively; 62% received
      second-line treatment (28% chemotherapy, 72% ALK TKI) with an associated RR, DCR,
      and PFS of 43.4%, 70%, and 4.7 (95% CI 4.0-8.1) months, respectively. The 2-year
      OS was 56.7% (95% CI 45.5-70.4%); median OS was not reached. CONCLUSION: The
      results of this real-life analysis suggest that the prognosis of NSCLC patients
      with theALK translocation may be better than that of the overall NSCLC
      population, but the outcomes were poorer than those of ALK+ NSCLC patients
      included in clinical studies.

PMID- 28762089
TI  - Secondary Metabolites from Higher Fungi.
AB  - Secondary metabolites of higher fungi (mushrooms) are an underexplored resource
      compared to plant-derived secondary metabolites. An increasing interest in
      mushroom natural products has been noted in recent years. This chapter gives a
      comprehensive overview of the secondary metabolites from higher fungi, with 765
      references highlighting the isolation, structure elucidation, biological
      activities, chemical syntheses, and biosynthesis of pigments, nitrogen-containing
      compounds, and terpenoids from mushrooms. Mushroom toxins are also included in
      each section.In a section on pigments of higher fungi, pigments are classified
      into four categories, namely, those from the shikimate-chorismate, acetate
      malonate, and mevalonate biosynthetic pathways, and pigments containing nitrogen,
      with 145 references covering the years 2010-2016.In a section on other nitrogen
      containing compounds of higher fungi, compounds are categorized primarily into
      nitrogen heterocycles, nucleosides, non-protein amino acids, cyclic peptides, and
      sphingolipids, with 65 references covering the years 2010-2016. In turn, in a
      section describing terpenoids of higher fungi, the sesquiterpenoids and
      diterpenoids are thoroughly elaborated, spanning the years 2001-2016, and 2009
      2016, respectively. The divergent biosynthetic pathways from farnesyl
      pyrophosphate to sesquiterpenoids are also described. Selected triterpenoids with
      novel structures and promising biological activities, including lanostanes and
      ergostanes, are reported from the genus Ganoderma, and the fungi Antrodia
      cinnamomea and Poria cocos. In addition, cucurbitanes and saponaceolides are also
      compiled in this section.

PMID- 28762090
TI  - Human Deiminases: Isoforms, Substrate Specificities, Kinetics, and Detection.
AB  - Peptidylarginine deiminase (PAD) enzymes are of enormous interest in biomedicine.
      They catalyze the conversion of a positively-charged guanidinium at an arginine
      side chain into a neutral ureido group. As a result of this conversion, proteins
      acquire the non-ribosomally encoded amino acid "citrulline". This imposes
      critical influences on the structure and function of the target molecules. In
      multiple sclerosis, myelin hyper-citrullination promotes demyelination by
      reducing its compaction and triggers auto-antibody production. Immune responses
      to citrulline-containing proteins play a central role in the pathogenesis of
      autoimmune diseases. Moreover, auto-antibodies, specific to citrullinated
      proteins, such as collagen type I and II and filaggrin, are early detectable in
      rheumatoid arthritis, serving as diagnostic markers of the disease. Despite their
      significance, little is understood about the role in demyelinating disorders,
      diversified cancers, and auto-immune diseases. To impart their biological and
      pathological effects, it is crucial to better understand the reaction mechanism,
      kinetic properties, substrate selection, and specificities of peptidylarginine
      deiminase isoforms.Many aspects of PAD biochemistry and physiology have been
      ignored in past, but, herein is presented a comprehensive survey to improve our
      current understandings of the underlying mechanism and regulation of PAD enzymes.

PMID- 28762091
TI  - Progress in the Chemistry of Naturally Occurring Coumarins.
AB  - Coumarins are the largest group of 1-benzopyran derivatives found in plants. The
      initial member of this group of compounds, coumarin (2H-1-benzopyran-2-one), a
      fragrant colorless compound, was first isolated from the Tonka bean (Dipteryx
      odorata, family Fabaceae) in 1820. The name coumarin comes from a French term for
      the tonka bean, coumarou. Since the discovery of coumarin, several of its
      derivatives, with umbelliferone (7-hydroxycoumarin) being the most common one,
      have been reported from various natural sources. The families Apiaceae,
      Asteraceae, and Rutaceae are the three major plant sources of
      coumarins.Generally, these plant secondary metabolites may be classified into
      simple, simple prenylated, simple geranylated, furano, pyrano, sesquiterpenyl and
      oligomeric coumarins. Using this standard classification, this chapter aims to
      present an account on the advances of the chemistry of naturally occurring
      coumarins, as reported in the literature during the period 2013-2015.In Sect. 1,
      the coumarins are introduced and their generic biosynthetic route discussed
      briefly. In Sect. 2, the largest of the three sections, various classes of
      natural coumarins are detailed, with their relevant structures and the citation
      of appropriate references. In a concluding section, it is highlighted that during
      the last 3 years, more than 400 coumarins have been reported in the literature.
      Many of these coumarins have been re-isolations of known compounds from known or
      new sources, most often associated with various biological activities. However, a
      substantial number of coumarins bearing new skeletons, especially dimers,
      prenylated furanocoumarins, sesquiterpenyl, and some unusual coumarins were also
      reported during the period of 2013-2015.Coumarin chemistry remains one of the
      major interest areas of phytochemists, especially because of their structural
      diversity and medicinal properties, along with the wide-ranging bioactivities of
      these compounds, inclusive of analgesic, anticoagulant anti-HIV, anti
      inflammatory, antimicrobial, antineoplastic, antioxidant, and immunomodulatory
      effects. Despite significant advancements in the extraction, isolation, structure
      elucidation and bioactivity testing of naturally occurring coumarins, only a
      marginal advancement has been observed recently in relation to the study of their
      biosynthesis.

PMID- 28762092
TI  - SOCS1 and pattern recognition receptors: TLR9 and RIG-I; novel haplotype
      associations in Egyptian fibrotic/cirrhotic patients with HCV genotype 4.
AB  - In this paper we explore the role of suppressor of cytokine signaling 1 (SOCS1)
      (rs243327), the regulator of toll-like receptor-9 (TLR9) (rs352140), retinoic
      acid inducible gene-I (RIG-I) (rs669260), and cluster of differentiation 152
      (CD152) (rs231776) in fibrotic/cirrhotic patients. Single nucleotide
      polymorphisms (SNPs) within these genes as well as haplotype analyses were
      performed on a cohort of 120 Egyptian fibrotic patients. Fibrosis had progressed
      from HCV genotype 4 infections. Using RT-PCR, SNPs were evaluated in the DNA
      collected from each patient using TaqMan(r) genotyping assays. A regression model
      was used to evaluate allelic and haplotypic associations with a
      fibrosis/cirrhotic scale. The necroinflammatory A score was adjusted for non
      genetic covariates. The genotype distributions for SOCS1 (rs243327) and TLR-9
      (rs352140) differed significantly between the F1-F3 and F3-F4 groups. On the
      other hand, the genotype distributions for RIG-I (rs669260) and CD152 (rs231776)
      genes did not significantly differ. The allele frequency was calculated using
      Hardy-Weinberg Equilibrium (HWE) for the SOCS1 (rs243327), RIG-I (rs669260), and
      CD152 (rs231776) genes. These calculated frequency values indicated the need to
      compare them to another population for that locus. However, TLR9 (rs352140) did
      not show similar results. The A allele in SOCS1, TLR9, and RIG-I SNPs was an
      adverse prognostic factor for liver fibrosis and liver activity. Haplotype
      analysis revealed a significant association between SOCS1 and TLR9 in
      fibrotic/cirrhotic patients. This indicated the presence of the A allele in
      either gene, which is considered a risk factor for the progression of liver
      disease to cirrhosis. SOCS1 rs243327, TLR9 rs352140, and RIG-I rs669260
      polymorphisms might affect liver pathophysiology and the cirrhotic outcome
      following genotype 4 HCV infection. Therefore, performing this specific SNP
      testing may be of value for the stratification of the population at risk.

PMID- 28762093
TI  - Evaluation of Mineral Concentrations in Maternal Serum Before and After Birth and
      in Newborn Cord Blood Postpartum-Preliminary Study.
AB  - The mineral levels in maternal serum change during pregnancy and may be
      correlated with those of newborn cord blood. The aim of this study was to
      evaluate the concentrations of calcium (Ca), magnesium (Mg), zinc (Zn), iron
      (Fe), and copper (Cu) in maternal blood before and after delivery and in
      umbilical cord vein and artery serum. The study was carried out in 64 Caucasian
      pregnant women who delivered in a district hospital in Greater Poland region,
      aged 28.1 +/- 5.4 years, with a mean gestational age of 39.2 +/- 1.3 weeks. Blood
      samples were taken from women 2-8 h before delivery and immediately after
      childbirth. The umbilical cord artery and vein blood of newborns was obtained
      immediately after childbirth. The levels of minerals in serum were determined by
      flame atomic absorption spectrometry. A significant drop in the concentrations of
      Mg (17.71 +/- 1.51 vs 17.07 +/- 1.61 MUg/ml; p < 0.007), Fe (1.08 +/- 0.46 vs
      0.82 +/- 0.35 MUg/ml; p < 0.0004), and Zn (0.63 +/- 0.17 vs 0.46 +/- 0.16; p <
      0.0001) in maternal serum was found after delivery. Moreover, higher levels of
      Ca, Fe, and Zn and lower levels of Cu were observed in the umbilical vein (Ca:
      102.80 +/- 7.80 MUg/ml; p < 0.0001, Fe: 1.96 +/- 0.43 MUg/ml; p < 0.0001, Zn:
      0.65 +/- 0.16 MUg/ml; p < 0.0001, Cu: 0.36 +/- 0.09 MUg/ml; p < 0.0001) and in
      the umbilical artery cord blood (Ca: 98.07 +/- 8.18 MUg/ml; p < 0.0001, Fe: 1.63
      +/- 0.30 MUg/ml; p < 0.0001, Zn: 0.65 +/- 0.15 MUg/ml; p < 0.0001, and Cu: 0.36
      +/- 0.10 MUg/ml; p < 0.0001) compared to the maternal serum (Ca: 85.05 +/- 10.76
      MUg/ml, Fe: 0.82 +/- 0.35 MUg/ml, Zn: 0.46 +/- 0.16 MUg/ml, and Cu: 1.90 +/- 0.35
      MUg/ml). Fe levels in the cord artery serum negatively correlated with blood loss
      during delivery (R = -0.48; p = 0.01), while the Ca concentration in the maternal
      serum after birth decreased with the age of the women (R = -0.25; p = 0.03). In
      conclusion, it seems that the process of birth alters the mineral levels in
      pregnant women's blood. Moreover, it was found that blood loss and the age of the
      mother are associated with mineral concentrations in the maternal serum and cord
      artery blood.

PMID- 28762094
TI  - SPECT but not PET remains as the working horse of the state of the art nuclear
      cardiac imaging laboratory: Con.

PMID- 28762095
TI  - Progressive loss of supination of the wrist. Benign intramuscular granular cell
      tumor (also known as Abrikossoff's tumor) of the right wrist.

PMID- 28762097
TI  - A Missense Variant p.Ala117Ser in the Transthyretin Gene of a Han Chinese Family
      with Familial Amyloid Polyneuropathy.
AB  - Familial amyloid polyneuropathy (FAP) is a dominantly inherited disorder. This
      study aims to explore the genetic features of a Han Chinese family with FAP,
      characterized by bloating, alternating diarrhea and constipation, and weakness in
      his feet. Amyloid presented histologically in the vessel walls of hepatic portal
      area and nerves of the surgically excised liver specimens from the proband by
      hematoxylin and eosin staining. Amyloid deposition was further confirmed with
      Congo red treatment. A c.349G>T transversion (p.Ala117Ser) in TTR gene exon 4 was
      identified in the proband with typical autonomic neuropathy and peripheral motor
      neuropathy, as well as in his asymptomatic son. The variant was not detected in
      200 normal ethnically matched controls. These findings provide new insights into
      FAP cause and diagnosis and have implications for genetic counseling.

PMID- 28762098
TI  - Preprocessing Prediction of Advanced Algorithms for Medical Imaging.
AB  - Advanced medical imaging algorithms (such as bone removal, vessel segmentation,
      or a lung nodule detection) can provide extremely valuable information to the
      radiologists, but they might sometimes be very time consuming. Being able to run
      the algorithms in advance can be a possible solution. However, we do not know
      which algorithm to run on a given dataset before it is actually used. It is
      possible to manually insert matching rules for preprocessing algorithms, but it
      requires high maintenance and does not work well in practice. This paper presents
      a dynamic machine learning solution for predicting which advanced visualization
      (AV) algorithm needs to be applied on a given series. The system gets a handful
      of free text DICOM tags as an input and builds a model in the clinical setting.
      It incorporates a Bag of Words (BOW) feature extractor and a Random Forest
      classifier. The approach was tested on two datasets from clinical sites which use
      different languages and varying scanner models. We show that even without feature
      extraction, sensitivity of above 90% can be reached on both of them. By using BOW
      feature extractor, precision and sensitivity can usually be further improved.
      Even on a noisy and highly unbalanced dataset, only around 100 samples were
      needed to reach sensitivity of above 80% and specificity of above 97%. We show
      how the solution can be part of a Smart Preprocessing mechanism in a viewing
      software. Using such a system will ultimately minimize the time to launch studies
      and improve radiologists reading time efficiency.

PMID- 28762099
TI  - Subjective evaluation of psychosocial well-being in children and youths with
      overweight or obesity: the impact of multidisciplinary obesity treatment.
AB  - PURPOSE: To investigate the effects of a multidisciplinary childhood obesity
      treatment programme on subjective evaluations of psychosocial well-being and
      quality of life. METHODS: This longitudinal observational study included 1291
      children, adolescents and young adults, 6-22 years of age, with overweight or
      obesity. At entry and after 2-82 months of obesity treatment, the patients
      evaluated the following domains of psychosocial well-being on a visual analogue
      scale: quality of life, mood, appetite, bullying, motivation for weight loss and
      body image satisfaction. The degree of overweight was calculated using a body
      mass index (BMI) standard deviation score (SDS) at each visit. RESULTS: At entry,
      the mean BMI SDS was 2.81 (range: 1.35-6.65, 95% confidence interval (95% CI):
      2.44-3.18). After a median of 14 months of treatment, the median reduction in BMI
      SDS was 0.29 (95% CI: 0.26-0.31, p < 0.0001). Improvements were observed in the
      domains of quality of life, mood, appetite, bullying and body image satisfaction
      (p < 0.0001). Larger reductions in BMI SDS were associated with greater
      improvements in the domains of quality of life (p = 0.001), mood (p = 0.04) and
      body image satisfaction (p < 0.0001), independent of BMI SDS at entry. However,
      improvements in psychosocial well-being were also observed in those increasing
      their BMI SDS (n = 315). CONCLUSIONS: In a large group of children and youths,
      psychosocial well-being improved during a multidisciplinary childhood obesity
      treatment programme, irrespective of the degree of obesity at treatment entry.
      Greater reductions in BMI SDS were associated with greater improvements in
      psychosocial well-being, but even in the group increasing their BMI SDS
      improvements were observed.

PMID- 28762100
TI  - Measuring quality of life in opioid-dependent people: a systematic review of
      assessment instruments.
AB  - PURPOSE: Opioid dependence is a chronic relapsing disorder. Despite increasing
      research on quality of life (QOL) in people with opioid dependence, little
      attention has been paid to the instruments used. This systematic review examines
      the suitability of QOL instruments for use in opioid-dependent populations and
      the instruments' quality. METHODS: A systematic search was performed in the
      databases Medline, PsycInfo, The Cochrane Library, and CINAHL. Articles were
      eligible if they assessed QOL of opioid-dependent populations using a validated
      QOL instrument. Item content relevance to opioid-dependent people was evaluated
      by means of content analysis, and instrument properties were assessed using
      minimum standards for patient-reported outcome measures. RESULTS: Eighty-nine
      articles were retrieved, yielding sixteen QOL instruments, of which ten were
      assessed in this review. Of the ten instruments, six were disease specific, but
      none for opioid dependence. Two instruments had good item content relevance. The
      conceptual and measurement model were described in seven instruments. Four
      instruments were developed with input from the respective target population.
      Eight instruments had low respondent and administrator burden. Psychometric
      properties were either not assessed in opioid-dependent populations or were
      inconclusive or moderate. CONCLUSIONS: No instrument scored perfectly on both the
      content and properties. The limited suitability of instruments for opioid
      dependent people hinders accurate and sensitive measurement of QOL in this
      population. Future research is in need of an opioid dependence-specific QOL
      instrument to measure the true impact of the disease on people's lives and to
      evaluate treatment-related services.

PMID- 28762101
TI  - Clinical outcomes and survival in pediatric patients initiating chronic dialysis:
      a report of the NAPRTCS registry.
AB  - BACKGROUND: The 2011 annual report of the North American Pediatric Renal
      Transplant Cooperative Study (NAPRTCS) registry comprises data on 6482 dialysis
      patients over the past 20 years of the registry. METHODS: The study compared
      clinical parameters and patient survival in the first 10 years of the registry
      (1992-2001) with the last decade of the registry (2002-2011). RESULTS: There was
      a significant increase in hemodialysis as the initiating dialysis modality in the
      most recent cohort (42% vs. 36%, p < 0.001). Patients in the later cohort were
      less likely to have a hemoglobin <10 g/dl [odds ratio (OR) 0.68; confidence
      interval (CI) 0.58-0.81; p < 0.001] and height z-score <2 standard deviations
      (SD) below average (OR 0.68, CI 0.59-0.78, p < 0.0001). They were also more
      likely to have a parathyroid hormone (PTH) level two times above the upper limits
      of normal (OR 1.39, CI 1.21-1.60, p < 0.0001). Although hypertension was common
      regardless of era, patients in the 2002-2011 group were less likely to have blood
      pressure >90th percentile (OR 1.39, CI 1.21-1.60, p < 0.0001), and a significant
      improvement in survival at 36 months after dialysis initiation was observed in
      the 2002-2011 cohort compared with the 1992-2001 cohort (95% vs. 90%,
      respectively). Cardiopulmonary causes were the most common cause of death in both
      cohorts. Young age, growth deficit, and black race were poor predictors of
      survival. CONCLUSIONS: The survival of pediatric patients on chronic dialysis has
      improved over two decades of dialysis registry data, specifically for children
      <1year.

PMID- 28762102
TI  - Weight Loss and Appetite Control in Women.
AB  - PURPOSE OF REVIEW: The aim of this review is to describe and discuss weight loss
      induced variations in appetite in women and factors responsible for these
      changes. RECENT FINDINGS: Studies have shown postweight loss increases in fasting
      and postprandial appetite in individuals engaged in weight loss trials,
      especially in women. Similarly, appetite-related peptides associated to the
      homeostatic control of feeding, such as leptin, ghrelin and peptide YY, were also
      found to be altered in way that promotes increased appetite after weight loss
      interventions. Sustained caloric deficits also drive increases in the frequency
      and strength of food cravings, food reward and seem to enhance oro-sensory
      sensations in women who lost weight. The menstrual cycle has also been to shown
      to influence caloric intake in women, more specifically food cravings. On the
      other hand, caloric restriction seems to increase cognitive restraint, decrease
      habitual disinhibition and susceptibility to hunger among women engaged in weight
      loss trials. Neural analysis corroborates these results, showing increased
      activation in brain areas involved in food reward and self-control processing. In
      conclusion, evidence supports that weight loss increases appetite sensations, and
      promotes changes in homeostatic and non-homeostatic control of feeding, which
      collectively seem to upregulate appetite in women.

PMID- 28762103
TI  - The Influence of Fathers on Children's Physical Activity and Dietary Behaviors:
      Insights, Recommendations and Future Directions.
AB  - PURPOSE OF REVIEW: Although fathers have an important influence on their
      children's well-being, their unique influence on child lifestyle behaviors has
      been largely overlooked in the literature. To inform and encourage future
      research, this paper provides an overview of existing studies that have examined
      the influence of fathers on the physical activity and dietary behaviors of their
      children. RECENT FINDINGS: While the available data indicate that fathers'
      behaviors and parenting practices likely play an important role in promoting
      healthy behaviors in children, the evidence base is limited by a reliance on
      observational designs and small, ungeneralizable samples. This paper also
      provides a summary of the methods, research findings, and experiential insights
      we have gained while conducting the "Healthy Dads, Healthy Kids" randomized
      controlled trials, which tested the efficacy and effectiveness of a socio
      culturally targeted program that engages fathers to improve their own health and
      the health of their children. The paper concludes with a series of
      recommendations for recruiting and engaging fathers and a summary of directions
      for future research.

PMID- 28762104
TI  - NGF Attenuates High Glucose-Induced ER Stress, Preventing Schwann Cell Apoptosis
      by Activating the PI3K/Akt/GSK3beta and ERK1/2 Pathways.
AB  - Diabetic peripheral neuropathy (DPN) is one of the most common and troublesome
      complications of diabetes mellitus. It has been demonstrated that nerve growth
      factor (NGF) exerts a pivotal role in the regulation of neuronal growth and the
      promotion of DPN recovery. However, the exact molecular mechanisms are not well
      understood. Recent studies have indicated that as a novel therapeutic target,
      endoplasmic reticulum (ER) stress participates in the onset and progression of
      DPN. In the present study, it has been demonstrated that NGF prevents the sciatic
      nerve from degeneration and demyelination in DPN rats. Thus, RSC 96 cells, which
      retain the characteristic features of Schwann cells (SCs), were cultured in
      medium containing 30 mM glucose (high glucose, HG) to mimic SCs in DPN mice. The
      50-ng/ml dose of NGF was identified to be the optimal concentration for treating
      an excessive ER stress level under HG conditions for 24 h. We found that NGF
      treatment significantly inhibits HG-induced ER stress and subsequently suppresses
      ER-related apoptosis. Further, NGF administration also activates the upstream
      signaling pathway of ER stress, PI3K/Akt/GSK3beta signaling and ERK1/2 signaling.
      Co-treatment with the PI3K inhibitor LY294002 or ERK1/2 inhibitor U0126
      significantly reverses the protective role of NGF on HG-induced excessive ER
      stress and subsequent apoptosis. These observations suggest that the
      neuroprotective role of NGF in DPN is mediated by the inhibition of excessive ER
      stress via the activation of the PI3K/Akt/GSK3beta and ERK1/2 signaling pathways.

PMID- 28762105
TI  - Disorganization of Oligodendrocyte Development in the Layer II/III of the
      Sensorimotor Cortex Causes Motor Coordination Dysfunction in a Model of White
      Matter Injury in Neonatal Rats.
AB  - We previously established neonatal white matter injury (WMI) model rat that is
      made by right common carotid artery dissection at postnatal day 3, followed by 6%
      hypoxia for 60 min. This model has fewer oligodendrocyte progenitor cells and
      reduced myelin basic protein (MBP) positive areas in the sensorimotor cortex, but
      shows no apparent neuronal loss. However, how motor deficits are induced in this
      model is unclear. To elucidate the relationship between myelination disturbance
      and concomitant motor deficits, we first performed motor function tests (gait
      analysis, grip test, horizontal ladder test) and then analyzed myelination
      patterns in the sensorimotor cortex using transmission electron microscopy (TEM)
      and Contactin associated protein 1 (Caspr) staining in the neonatal WMI rats in
      adulthood. Behavioral tests revealed imbalanced motor coordination in this model.
      Motor deficit scores were higher in the neonatal WMI model, while hindlimb ladder
      stepping scores and forelimb grasping force were comparable to controls.
      Prolonged forelimb swing times and decreased hindlimb paw angles on the injured
      side were revealed by gait analysis. TEM revealed no change in myelinated axon
      number and the area g-ratio in the layer II/III of the cortex.
      Electromyographical durations and latencies in the gluteus maximus in response to
      electrical stimulation of the brain area were unchanged in the model. Caspr
      staining revealed fewer positive dots in layers II/III of the WMI cortex,
      indicating fewer and/or longer myelin sheath. These data suggest that
      disorganization of oligodendrocyte development in layers II/III of the
      sensorimotor cortex relates to imbalanced motor coordination in the neonatal WMI
      model rat.

PMID- 28762106
TI  - Depression Symptoms in Haemodialysis Patients Predict All-Cause Mortality but Not
      Kidney Transplantation: A Cause-Specific Outcome Analysis.
AB  - Background: Depression is common in haemodialysis (HD) patients and associated
      with poor outcomes. Purpose: To evaluate whether depression symptoms predict
      survival and transplantation in a large sample of haemodialysis patients using
      cause-specific survival models. Methods: Survival data was collected between
      April 2013 and November 2015, as part of the screening phase of a multicentre
      randomised placebo-controlled trial of sertraline in HD patients. Depression was
      measured using the Beck Depression Inventory-II (BDI-II) and the Patient Health
      Questionnaire-9 (PHQ-9). Demographic and clinical data were collected via a self
      report questionnaire and medical records. Competing risk survival analysis
      involved cause-specific and subdistribution hazard survival models. All models
      were adjusted for appropriate covariates including co-morbidity and C-reactive
      protein (CRP) in a subanalysis. Results: Of 707 cases available for analysis,
      there were 148 deaths. The mean survival time was 787.5 days. Cumulative survival
      at 12 months was 88.5%. During the study follow-up period, there were 92
      transplants. The cumulative transplant event rate at 12 months was 7.8%. In
      separate adjusted models, depression symptoms predicted mortality (BDI-II HR =
      1.03 95% CI 1.01, 1.04; PHQ-9 HR = 1.04 95% CI 1.01, 1.06). With respect to
      screening cut-off scores, a PHQ-9 >= 10 was associated with mortality (HR = 1.51
      95% CI 1.01, 2.19) but not a BDI-II >= 16. Depression symptoms were not
      associated with time to transplantation in either cause-specific or
      subdistribution model. Conclusions: Consistent with past findings in HD patients,
      depression symptoms predicted survival but were not associated with kidney
      transplantation. Suitable treatments for depression need further evaluation, and
      their impact upon quality of life and clinical outcomes determined. Trial
      Registration Number: (ISRCTN06146268).

PMID- 28762107
TI  - PMM2-CDG and sensorineural hearing loss.

PMID- 28762108
TI  - Trigeminal neuropathy associated with an enlarging arachnoid cyst in Meckel's
      cave: case report, management strategy and review of the literature.
AB  - We describe a rare case and novel management strategy of painful trigeminal
      neuropathy caused by an arachnoid cyst confined to Meckel's cave. A 57-year-old
      female presented with several years of progressive trigeminal pain and signs of
      trigeminal deafferentation, including sensory loss, corneal anesthesia and
      mastication muscle atrophy. Medical treatment with carbamazepine provided partial
      and temporary pain control. Surgical treatment was eventually performed by
      aspiration of the arachnoid cyst through the foramen ovale using a percutaneous
      approach. The patient experienced relief of pain and improvement of numbness and
      muscle strength. To our knowledge, this is the first case description of a
      percutaneous drainage of a Meckel's cave arachnoid cyst.

PMID- 28762109
TI  - Dual lumbar bronchogenic and arachnoid cyst presenting with sciatica and left
      foot drop.
AB  - INTRODUCTION: Spinal bronchogenic cysts are rare findings, with only four cases
      of lumbar bronchogenic cysts reported in the literature. All of these
      bronchogenic cysts involved the conus medullaris. We present the first case of a
      lumbar bronchogenic cyst and arachnoid cyst arising from the cauda equina in a 68
      year-old male. Uniquely, this bronchogenic cyst also contained components of an
      arachnoid cyst. METHODS: Magnetic resonance imaging (MRI) demonstrated a
      compressive cystic lesion at the level of the L3 vertebra splaying the cauda
      equina. An L3/L4 laminectomy was performed with marsupialisation of the cyst.
      RESULTS: Histological examination revealed pseudostratified ciliated columnar
      epithelium confirming the diagnosis of a bronchogenic cyst, as well as a pleated
      fibrovascular tissue lined by sparsely spaced small monomorphic arachnoidal
      cells, indicating an arachnoid cyst. CONCLUSION: We demonstrate that bronchogenic
      cysts can be successfully treated with marsupialisation.

PMID- 28762110
TI  - Technique for rerouting a bridging vein that hinders the anterior
      interhemispheric approach: a technical note.
AB  - BACKGROUND: The frontal bridging vein, which is the venous drainage route of the
      frontal cortex into the superior sagittal sinus (SSS), sometimes poses an
      obstacle in the anterior interhemispheric approach during surgery for anterior
      cerebral artery aneurysms. Although severe complications including venous
      infarction or edema due to damage to the bridging vein are well known, only a few
      reports have discussed how to avoid venous injury when we must sacrifice the
      bridging vein to obtain an appropriate surgical field. This report describes a
      microvascular technique performed in two patients who underwent rerouting of the
      bridging vein to obtain an appropriate anterior interhemispheric surgical
      corridor to treat a ruptured anterior cerebral artery aneurysm. The hindering
      bridging vein was resected from the entrance to the SSS and anastomosed toward
      the adjacent cortical vein. METHODS: A 65-year-old male and a 43-year-old male
      were admitted to our hospital for sudden headache. Computed tomography, magnetic
      resonance angiogram, or digital subtraction angiography demonstrated a
      subarachnoid hemorrhage and an anterior cerebral artery aneurysm in both
      patients. In both cases, a relatively robust bridging vein, which appeared
      problematic to sacrifice, was draining into the SSS, resulting in a limited
      surgical corridor. Thus, we performed cortical vein reconstruction, and the
      aneurysms were successfully clipped under a wider surgical view. RESULTS: We
      confirmed completed clipping without postoperative venous complications. One
      patient demonstrated patency of reconstructed venous flow by digital subtraction
      angiography. No apparent cognitive impairment was seen in either patient.
      CONCLUSIONS: This technique may be useful for obtaining an appropriate surgical
      corridor when the frontal bridging vein may be damaged.

PMID- 28762111
TI  - Unruptured brain AVMs: it's time we worked together to integrate care and
      clinical research.

PMID- 28762112
TI  - Targeted next-generation sequencing identifies clinically relevant mutations in
      patients with chronic neutrophilic leukemia at diagnosis and blast crisis.
AB  - PURPOSE: Chronic neutrophilic leukemia is a rare form of myeloproliferative
      neoplasm characterized by mature neutrophil hyperleukocytosis. The majority of
      patients harbor somatic mutations of CSF3R gene and are potentially amenable to
      targeted therapy with JAK inhibitors. The incidence and clinical significance of
      additional mutations requires clarification. MATERIALS AND METHODS: A next
      generation sequencing approach for myeloid malignancy-associated mutations was
      applied to diagnostic and matched blast crisis samples from four chronic
      neutrophilic leukemia patients. RESULTS: Next-generation sequencing confirmed the
      CSF3R T618I in all patients with identification of concurrent SRSF2, SETBP1, NRAS
      and CBL mutations at diagnosis. At blast crisis, clonal evolution was evidenced
      by an increased CSF3R T618I allele frequency and by loss or acquisition of CBL
      and NRAS mutations. CONCLUSION: The diagnostic utility of a targeted next
      generation sequencing approach was clearly demonstrated with the identification
      of additional mutations providing the potential for therapeutic stratification of
      chronic neutrophilic leukemia patients.

PMID- 28762113
TI  - Implications of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA
      ALCL) for Breast Cancer Reconstruction: An Update for Surgical Oncologists.
AB  - Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare
      disease that has been diagnosed in an extremely small proportion of women with
      breast implants. The pathogenesis of this disease is currently poorly understood,
      but it appears to be related to textured implants. Recent high-profile media
      coverage of this rare clinical entity is likely to cause considerable anxiety for
      breast cancer patients who have undergone alloplastic breast reconstruction. The
      purpose of this review is to provide surgical oncologists with an evidence-based
      overview of the incidence, diagnosis, and management of BIA-ALCL with a
      particular emphasis on breast reconstruction cases. It is essential that surgical
      oncologists are familiar with BIA-ALCL, because although it is extremely rare,
      early recognition and surgical resection will be curative in many cases.

PMID- 28762115
TI  - Erratum to: Intraoperative Tumor Detection Using a Ratiometric Activatable
      Fluorescent Peptide: A First-in-Human Phase 1 Study.

PMID- 28762114
TI  - The Optimal Treatment Plan to Avoid Axillary Lymph Node Dissection in Early-Stage
      Breast Cancer Patients Differs by Surgical Strategy and Tumor Subtype.
AB  - BACKGROUND: Strategies to reduce the likelihood of axillary lymph node dissection
      (ALND) include application of Z0011 or use of neoadjuvant chemotherapy (NAC).
      Indications for ALND differ by treatment plan, and nodal pathologic complete
      response rates after NAC vary by tumor subtype. This study compared ALND rates
      for cT1-2N0 tumors treated with upfront surgery versus those treated with NAC.
      METHODS: The ALND rates for cT1-2N0 breast cancer patients were compared by tumor
      subtype among women undergoing upfront surgery to NAC. Multivariable analysis
      with control for age, cT stage, and lymphovascular invasion, and stratification
      by subtype was performed. RESULTS: The study identified 1944 cancers in 1907
      women who underwent sentinel lymph node (SLN) biopsy with or without ALND (669
      upfront breast-conserving surgeries [BCSs], 1004 upfront mastectomies, 271 NACs).
      Compared with the NAC group, the ALND rates in the BCS group were lower for
      estrogen receptor (ER), progesterone receptor-positive (PR+), human epidermal
      growth factor 2-negative (HER2-) tumors (15 vs 34%; p < 0.001). The ALND rates in
      the upfront mastectomy group were higher than in the NAC group for HER2+ or TN
      tumors. In the multivariable analysis, receipt of NAC compared with upfront BCS
      remained significantly associated with higher odds of ALND in the ER/PR+ HER2-
      subtype (hazard ratio [HR], 3.35; p < 0.001), whereas NAC versus upfront
      mastectomy remained significantly associated with lower odds of ALND in the HER2+
      and TN subtypes (HR for HER2+, 0.19, p < 0.001; HR for TN, 0.25, p = 0.007).
      CONCLUSION: The study showed that ALND rates differ according to surgery type and
      tumor subtype secondary to differing ALND indications and nodal response to NAC.
      These factors can be used to personalize treatment planning to minimize ALND risk
      for patients with early-stage breast cancer.

PMID- 28762116
TI  - Merkel Cell Carcinoma of the Head and Neck: Recommendations for Diagnostics and
      Treatment.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive tumor that often
      occurs in the head and neck region. Because of these features, the
      classifications and diagnostic and treatment regimens are frequently modified.
      Especially in the anatomically complex head and neck region, it is crucial to be
      aware of the current recommendations for diagnostics and treatment of MCC to
      ensure appropriate treatment. This overview aims to summarize the currently
      available literature. METHODS: The authors reviewed the relevant literature and
      international guidelines for MCC from 2012 to 2017 with respect to epidemiology
      and prognosis, diagnostic procedures and imaging, surgery, radiation, systemic
      treatment, and aftercare. These results were compared with existing guidelines,
      some of them current, and recommendations were derived. RESULTS: Marked
      developments in imaging have resulted in an increased use of functional imaging.
      The surgical concepts have changed regarding safety margins and the use of
      sentinel node biopsies. In systemic treatment, a move from conventional agents
      toward immuno-oncology can be observed. CONCLUSIONS: For staging, it is important
      to be as exact as possible using functional imaging (e.g., positron emission
      tomography/computed tomography scan), especially in the head and neck area with
      its complex lymph drainage. This often plays an especially important role in
      early stages of the tumor, when the resection margin can be reduced to preserve
      the organ. Aftercare also should include functional imaging. In an advanced,
      metastatic stage, immuno-oncology (PD-1, PD-L1, CTLA-4) is superior to the
      previous methods of systemic treatment.

PMID- 28762117
TI  - Long-term costs and survival of prostate cancer: a population-based study.
AB  - PURPOSE: There is a rising interest in measuring the societal burden of
      malignancies including prostate cancer. However, population-based studies
      reporting incidence costs of prostate cancer in the long term are lacking in
      Europe. The objectives of the study are to analyse the long-term costs and
      survival of prostate cancer patients treated by radical prostatectomy (RP) or
      conservative management (nRP). METHODS: A retrospective claims data analysis of
      the National Health Insurance Found Administration of Hungary between 01.01.2002
      and 31.10.2013 was carried out. Annual incidence costs related to prostate cancer
      and overall survival were calculated for a cohort of patients diagnosed between
      2002 and 2005. RESULTS: Altogether 17,642 patients were selected; 2185 (12%) of
      them have undergone RP. The annual incidence rate ranged between 4177 and 4736
      cases. Mean age of RP and nRP patients was 59.4 (SD 5.9) and 71.0 (8.4) years,
      respectively. The mean survival time of the RP patients was significantly longer
      compared to nRP patients both in the total sample (11.2 vs. 7.4 years; p < 0.001)
      and in the subgroup <70 years (11.3 vs. 8.8 years; p < 0.001). At the end of the
      12-year follow-up, RP patients had a higher (0.83 vs. 0.68), while nRP patients
      had a slightly lower (0.35 vs. 38) probability of being alive compared with the
      age-matched general male population. The long-term cumulative costs of the RP and
      nRP patients amounted to ?4448 and ?8616. The main driver of the cost difference
      was the high drug costs in the nRP group. CONCLUSIONS: To our knowledge, this
      study applied the longest time-window in reporting population-based incidence
      costs in Europe. We found that not only RP patients lived longer but they had
      significantly lower total long-term costs than nRP patients. Therefore, radical
      prostatectomy is a cost-effective strategy in prostate cancer.

PMID- 28762119
TI  - [Sexual and contraceptive behaviour of young people throughout the decades :
      German Federal Centre for Health Education: Selected survey results on youth
      sexuality].
AB  - The study Youth Sexuality 2015 by the German Federal Centre for Health Education
      (BZgA) makes clear the changes in the sexual and contraceptive behaviour of
      teenagers and young adults over the last 35 years. Among young Germans, we can
      see that there is now more gender similarity both with regard to the age at which
      intercourse first takes place, and in contraceptive behaviour. The proportion of
      those who take no contraceptive precautions when they have intercourse for the
      first time is now 6% among male German teenagers and 8% among female ones, a
      lower figure than ever previously recorded. Communication about contraception,
      both at home and between partners, is making a substantial contribution to
      responsible contraceptive behaviour on the part of teenagers and young adults.
      Alongside education about sexuality in the family and at school, there are also
      structural influences on the positive developments in Germany. And yet there are
      still target groups that are inadequately reached. Many migrants are less well
      informed about bodily processes, their contraceptive practice is not so good, and
      their cultural/religious background also tends to mean that they are excluded
      from access to information. Education and social deprivation continue to be
      important factors in differences in sexual and contraceptive behaviour. In this
      area, pro-active efforts are necessary.

PMID- 28762118
TI  - Laparoscopic and robotic nephroureterectomy: does lymphadenectomy have an impact
      on the clinical outcome?
AB  - PURPOSE: To evaluate the effect of lymphadenectomy (LND) in conjunction with
      nephroureterectomy on cancer-specific mortality (CSM) and overall survival (OS)
      for patients with muscle-invasive UTUC. METHODS: A retrospective, multicenter
      study of patients with UTUC, clinical stage N0M0, who underwent
      nephroureterectomy between January 2008 and December 2014 was conducted. Outcome
      measures were OS and CSM. RESULTS: In total, 298 patients underwent robot
      assisted or laparoscopic radical nephroureterectomy with a final histological
      diagnosis of UTUC. LND was performed in 46 (15.4%). One hundred and seventy-two
      patients (62%) had non-muscle-invasive disease (NMID); 105 patients (38%) had
      muscle-invasive disease (MID). Median time of follow-up was 43.5 months (95% CI
      36.0-47.2). For patients with MID, the 5-year cumulative incidence of all-cause
      mortality and CSM was 73.5% (95% CI 60.4-86.6) and 52.4% (95% CI 38.9-65.9),
      respectively (p < 0.0001). There was no significant difference in OS between
      patients with N1 and patients with N0 disease (p = 0.53). The 5-year OS rates
      were 30.5% (95% CI 6.6-54.4) and 25.7% (95% CI 10.9-40.5), respectively. This
      study is limited by its retrospective nature. There may also have been bias in
      the selection of patients undergoing LND. CONCLUSIONS: Five-year OS and CSM are
      comparable between patients with N1 and N0 MID. This evidence may support the use
      of the LND procedure in patients with muscle-invasive UTUC.

PMID- 28762120
TI  - [The Zanzu web portal : A contribution to the sexual health of migrants].
AB  - BACKGROUND: "Zanzu - my body in words and images" - zanzu.de is a multilingual
      web portal that brings together information about different aspects of sexual
      health. It was developed to address specific needs of migrants, including
      barriers to access. Zanzu provides quality-assured information on the topics of
      body, sexuality, HIV/STIs, family planning, sexuality and rights. METHOD: A few
      months after launching the web portal, a formative evaluation was conducted. The
      following questions were central in the evaluation: Can the web portal be used in
      the context of counseling? What experiences have there been with various types of
      deployment and how do intermediaries (i. e., counselors) assess the portal?
      RESULTS: The results confirm that Zanzu has already contributed positively to
      counselling migrants and that the comprehensive nature of the service is strongly
      welcomed. A few of the interviewees acknowledged it had been challenging to
      integrate a digital service into a conventional counselling session. In addition,
      there were questions about the suitability of some of the illustrations for all
      people being counselled. DISCUSSION: Access to information is a precondition to
      take self-determined decisions. This is equally true in the sensitive field of
      sexual and reproductive health. A few months after its launch, Zanzu has already
      succeeded in providing more information to an important population. The ideas for
      improvement that have been gathered in the framework of the present evaluation
      will be the basis for the ongoing development of Zanzu, making it even better
      able to meet the needs of different target groups and in different contexts.

PMID- 28762121
TI  - [In-patient hospital care of selected sexual disorders : An analysis of data from
      the German Federal Statistical Office from 2000 to 2014].
AB  - BACKGROUND: Patients with the ICD-10 sexual disorders F52, F64, F65, and F66 are
      treated by a variety of medical disciplines. Until now, there has been a paucity
      of data regarding which sexual disorders are treated by means of in-patient
      hospital care and whether changes have occurred over time. OBJECTIVES: The aim of
      this study is to examine how many patients with sexual disorders that are
      classified by ICD-10 chapter V (F) as "mental" are treated as in-patients.
      METHODS: Diagnosis data regarding German hospital care, which have been published
      annually since 2000 by the German Federal Statistical Office (Destatis), are
      analysed. RESULTS: Since 2000, the number of in-patients with disorders of gender
      identity (F64) has increased 2.6-fold. Hospital treatment of sexual dysfunctions
      (F52) as a primary diagnosis is decreasing, whereas a significantly higher number
      of in-patients are treated with F52 as a secondary diagnosis. In-patients with
      F64 are mostly treated in urology and gynaecology departments or by surgeons, and
      76.0-81.1% of F52 cases in urology. In-patients with paraphilic disorders (F65)
      or psychological and behavioral disorders associated with sexual development and
      orientation (F66) are rarely but almost exclusively treated in psychiatric or
      psychotherapeutic departments. DISCUSSION: The data indicate that most in-patient
      hospital treatment for primary diagnoses of sexual disorders are somatic
      treatments for erectile dysfunction (F52.2) and transsexualism (F64.0). Owing to
      a steady increase in cases with F64.0 diagnoses, a growth in demand for
      competence in sexual medicine can be noted, especially in the surgical
      disciplines. Causes of the distribution and the increase in in-patient numbers
      are discussed. Further research is required, particularly concerning the
      treatment of in-patients with F52 and F64 secondary diagnoses.

PMID- 28762122
TI  - [Quality development within interdisciplinary transgender healthcare : Results
      and implications of a participatory research project].
AB  - Both internationally and nationally, the objective has been set to offer
      specialized, coordinated, and interdisciplinary treatment to individuals with
      rare clinical needs, such as trans individuals (e. g., transsexual, transgender).
      The Interdisciplinary Transgender Health Care Center Hamburg (ITHCCH) is the
      first and only center in Germany to integrate all disciplines relevant to trans
      healthcare (THC).The research project seeks to generate valid information to
      support quality development and assure high-quality treatment at the ITHCCH. This
      was done by (a) investigating needs and concerns of trans individuals regarding
      interdisciplinary THC, and (b) analyzing attitudes and interests of key
      stakeholders.Using a participatory approach involving a work group
      (representatives of trans support groups and local THC professionals),
      researchers developed an online survey focusing on trans individuals' needs and
      concerns. Data from N = 415 trans-identified participants were analyzed using
      quantitative and qualitative methods. In addition, a short survey was used to
      record key stakeholders' attitudes and interests towards the ITHCCH.Healthcare
      offers accessed by trans individuals as part of transition related treatment vary
      in focus and number. For example, take-up numbers of genital surgery differ
      between binary and non-binary trans individuals. Crucial aspects impacting on THC
      quality are structural characteristics, communication/social aspects,
      individuality, and professionalism/quality.To ensure successful, high-quality
      interdisciplinary THC, feedback from (potential) patients and stakeholders is
      crucial. In addition, both structural development and optimizing individuality
      and flexibility throughout the treatment process are key. This poses a
      considerable challenge to the sector of THC provision.

PMID- 28762123
TI  - Differential immune responses of Monochamus alternatus against symbiotic and
      entomopathogenic fungi.
AB  - Monochamus alternatus, the main vector beetles of invasive pinewood nematode, has
      established a symbiotic relationship with a native ectotrophic fungal symbiont,
      Sporothrix sp. 1, in China. The immune response of M. alternatus to S. sp. 1 in
      the coexistence of beetles and fungi is, however, unknown. Here, we report that
      immune responses of M. alternatus pupae to infection caused by ectotrophic
      symbiotic fungus S. sp. 1 and entomopathogenic fungus Beauveria bassiana differ
      significantly. The S. sp. 1 did not kill the beetles while B. bassiana killed all
      upon injection. The transcriptome results showed that the numbers of
      differentially expressed genes in M. alternatus infected with S. sp. 1 were 2
      fold less than those infected with B. bassiana at 48 hours post infection. It was
      noticed that Toll and IMD pathways played a leading role in the beetle's immune
      system when infected by symbiotic fungus, but upon infection by entomopathogenic
      fungus, only the Toll pathway gets triggered actively. Furthermore, the beetles
      could tolerate the infection of symbiotic fungi by retracing their Toll and IMD
      pathways at 48 h. This study provided a comprehensive sequence resource of M.
      alternatus transcriptome for further study of the immune interactions between
      host and associated fungi.

PMID- 28762124
TI  - A randomized trial of early detection of clinically significant prostate cancer
      (ProScreen): study design and rationale.
AB  - The current evidence of PSA-based prostate cancer screening shows a reduction in
      cause-specific mortality, but with substantial overdiagnosis. Recently, new
      developments in detection of clinically relevant prostate cancer include multiple
      kallikreins as biomarkers besides PSA, and multiparametric magnetic resonance
      imaging (mpMRI) for biopsy decision. They offer opportunities for improving the
      outcomes in screening, particularly reduction in overdiagnosis and higher
      specificity for potentially lethal cancer. A population-based randomized
      screening trial will be started, with 67,000 men aged 55-67 years at entry. A
      quarter of the men will be allocated to the intervention arm, and invited to
      screening. The control arm will receive no intervention. All men in the screening
      arm will be offered a serum PSA determination. Those with PSA of 3 ng/ml or
      higher will have an additional multi-kallikrein panel and those with indications
      of increased risk of clinically relevant prostate cancer will undergo mpMRI. Men
      with a malignancy-suspect finding in MRI are referred to targeted biopsies.
      Screening interval is 6 years for men with baseline PSA < 1.5 ng/ml, 4 years with
      PSA 1.5-3.0 and 2 years if initial PSA > 3. The main outcome of the trial is
      prostate cancer mortality, with analysis at 10 and 15 years. The statistical
      power is sufficient for detecting a 28% reduction at 10 years and 22% at 15
      years. The proposed study has the potential to provide the evidence to justify
      screening as a public health policy if mortality benefit can be sustained with
      substantially reduced overdiagnosis.

PMID- 28762125
TI  - Progress in Definition, Prevention and Treatment of Fungal Infections in Cystic
      Fibrosis.
AB  - Cystic fibrosis (CF) is a chronic lethal multi-system condition; however, most of
      the morbidity and mortality is dependent on the status of the respiratory system.
      Progressive respiratory decline is mediated by chronic infection and
      inflammation, punctuated by important acute events known as pulmonary
      exacerbations which can lead to accelerated decline. The main bacterial species
      causing infections include Pseudomonas aeruginosa, Staphylococcus aureus,
      Haemophilus influenzae and Achromobacter xylosoxidans. In addition to bacteria,
      fungi are detected in a significant number of patients. The impact of fungal
      colonization of the airways is still not completely elucidated, but an increasing
      body of evidence suggests an important role for moulds and yeasts. Although
      fungal infections are rare, fungi can cause severe pneumonia requiring
      appropriate targeted treatment. The most common fungi in respiratory samples of
      patients with CF are Aspergillus fumigatus, Aspergillus terreus and Scedosporium
      species for filamentous fungi, and yeasts such as Candida albicans and Candida
      glabrata. Therapeutic strategies depend on the detected fungus and the underlying
      clinical status of the patient. The antifungal therapy can range from a simple
      monotherapy up to a combination of three different drugs. Treatment course may be
      indicated in some patients for two weeks and in others for up to six months, and
      in rare cases even longer. New antifungal drugs have been developed and are being
      tested in clinical studies offering the hope of therapeutic alternatives to
      existing drugs. Identifying relevant risk factors and diagnostic criteria for
      fungal colonization and infection is crucial to enabling an adequate prevention,
      diagnosis and treatment.

PMID- 28762126
TI  - Systematic scoping review of patients' perceived needs of health services for
      osteoporosis.
AB  - Health service planners, administrators and providers need to understand the
      patients' perspective of health services related to osteoporosis to optimise
      health outcomes. The aims of this study were to systematically identify and
      review the literature regarding patients' perceived health service needs relating
      to osteoporosis and osteopenia. A systematic scoping review was performed of
      publications in MEDLINE, EMBASE, CINAHL and PsycINFO (1990-2016). Descriptive
      data regarding study design and methodology were extracted and risk of bias
      assessed. Aggregates of patients' perceived needs of osteoporosis health services
      were categorised. Thirty-three studies (19 quantitative and 14 qualitative) from
      1027 were relevant. The following areas of perceived need emerged: (1) patients
      sought healthcare from doctors to obtain information and initiate management.
      They were dissatisfied with poor communication, lack of time and poor continuity
      of care. (2) Patients perceived a role for osteoporosis pharmacotherapy but were
      concerned about medication administration and adverse effects. (3) Patients
      believed that exercise and vitamin supplementation were important, but there is a
      lack of data examining the needs for other non-pharmacological measures such as
      smoking cessation and alcohol. (4) Patients wanted diagnostic evaluation and
      ongoing surveillance of their bone health. This review identified patients' needs
      for better communication with their healthcare providers. It also showed that a
      number of important cornerstones of therapy for osteoporosis, such as
      pharmacotherapy and exercise, are identified as important by patients, as well as
      ongoing surveillance of bone health. Understanding patients' perceived needs and
      aligning them with responsive and evidence-informed service models are likely to
      optimise patient outcomes.

PMID- 28762127
TI  - Microdialysis as an Important Technique in Systems Pharmacology-a Historical and
      Methodological Review.
AB  - Microdialysis has contributed with very important knowledge to the understanding
      of target-specific concentrations and their relationship to pharmacodynamic
      effects from a systems pharmacology perspective, aiding in the global
      understanding of drug effects. This review focuses on the historical development
      of microdialysis as a method to quantify the pharmacologically very important
      unbound tissue concentrations and of recent findings relating to modeling
      microdialysis data to extrapolate from rodents to humans, understanding
      distribution of drugs in different tissues and disease conditions. Quantitative
      microdialysis developed very rapidly during the early 1990s. Method development
      was in focus in the early years including development of quantitative
      microdialysis, to be able to estimate true extracellular concentrations.
      Microdialysis has significantly contributed to the understanding of active
      transport at the blood-brain barrier and in other organs. Examples are presented
      where microdialysis together with modeling has increased the knowledge on tissue
      distribution between species, in overweight patients and in tumors, and in
      metabolite contribution to drug effects. More integrated metabolomic studies are
      still sparse within the microdialysis field, although a great potential for
      tissue and disease-specific measurements is evident.

PMID- 28762128
TI  - Physicochemical Characterization of Iron Carbohydrate Colloid Drug Products.
AB  - Iron carbohydrate colloid drug products are intravenously administered to
      patients with chronic kidney disease for the treatment of iron deficiency anemia.
      Physicochemical characterization of iron colloids is critical to establish
      pharmaceutical equivalence between an innovator iron colloid product and generic
      version. The purpose of this review is to summarize literature-reported
      techniques for physicochemical characterization of iron carbohydrate colloid drug
      products. The mechanisms, reported testing results, and common technical pitfalls
      for individual characterization test are discussed. A better understanding of the
      physicochemical characterization techniques will facilitate generic iron
      carbohydrate colloid product development, accelerate products to market, and
      ensure iron carbohydrate colloid product quality.

PMID- 28762129
TI  - Phytodetoxification of TNT by transplastomic tobacco (Nicotiana tabacum)
      expressing a bacterial nitroreductase.
AB  - KEY MESSAGE: Expression of the bacterial nitroreductase gene, nfsI, in tobacco
      plastids conferred the ability to detoxify TNT. The toxic pollutant 2,4,6
      trinitrotoluene (TNT) is recalcitrant to degradation in the environment.
      Phytoremediation is a potentially low cost remediation technique that could be
      applied to soil contaminated with TNT; however, progress is hindered by the
      phytotoxicity of this compound. Previous studies have demonstrated that plants
      transformed with the bacterial nitroreductase gene, nfsI have increased ability
      to tolerate and detoxify TNT. It has been proposed that plants engineered to
      express nfsI could be used to remediate TNT on military ranges, but this could
      require steps to mitigate transgene flow to wild populations. To address this, we
      have developed nfsI transplastomic tobacco (Nicotiana tabacum L.) to reduce
      pollen-borne transgene flow. Here we have shown that when grown on solid or
      liquid media, the transplastomic tobacco expressing nfsI were significantly more
      tolerant to TNT, produced increased biomass and removed more TNT from the media
      than untransformed plants. Additionally, transplastomic plants expressing nfsI
      regenerated with high efficiency when grown on medium containing TNT, suggesting
      that nfsI and TNT could together be used to provide a selectable screen for
      plastid transformation.

PMID- 28762131
TI  - Schizandra chinensis exhibits phytoestrogenic effects by regulating the
      activation of estrogen receptor-alpha and -beta.
AB  - OBJECTIVE: To investigate the phytoestrogenic effects of Schizandra chinensis
      (SC) extract by regulating the activation of estrogen receptor. METHODS: Western
      blotting assay was performed to investigate the effect of SC extract (1, 10, 100
      MUg/mL) on the expression of estrogen receptor (ER)-alpha and -beta in MCF-7
      human breast cancer cells. Cell viability and the levels of c-fos and c-Jun were
      analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay and Western blot analysis, respectively, to further confirm the anti-cancer
      effect of SC extract. RESULTS: SC extract increased the expressions of ER-alpha
      and -beta (P<0.001), whereas cell viability and the expressions of growth factors
      (c-fos and c-Jun) were inhibited (P< and <0.001, respectively) following
      treatment. CONCLUSIONS: SC extract has phytoestrogenic effects, and its
      biological action includes ER binding ability with low cancer risk. Therefore, SC
      might be a potential source for the development of a new alternative to hormone
      therapy in menopause.

PMID- 28762130
TI  - Modelling coupled within host and population dynamics of [Formula: see text] and
      [Formula: see text] HIV infection.
AB  - Most existing models have considered the immunological processes occurring within
      the host and the epidemiological processes occurring at population level as
      decoupled systems. We present a new model using continuous systems of non linear
      ordinary differential equations by directly linking the within host dynamics
      capturing the interactions between Langerhans cells, CD4[Formula: see text] T
      cells, R5 HIV and X4 HIV and the without host dynamics of a basic compartmental
      HIV/AIDS model. The model captures the biological theories of the cells that take
      part in HIV transmission. The study incorporates in its analysis the differences
      in time scales of the fast within host dynamics and the slow without host
      dynamics. In the mathematical analysis, important thresholds, the reproduction
      numbers, were computed which are useful in predicting the progression of the
      infection both within the host and without the host. The study results showed
      that the model exhibits four within host equilibrium points inclusive of three
      endemic equilibria whose effects translate into different scenarios at the
      population level. All the endemic equilibria were shown to be globally stable
      using Lyapunov functions and this is an important result in linking the within
      host dynamics to the population dynamics, because the disease free equilibrium
      point ceases to exist. The effects of linking were observed on the endemic
      equilibrium points of both the within host and population dynamics. Linking the
      two dynamics was shown to increase in the viral load within the host and increase
      in the epidemic levels in the population dynamics.

PMID- 28762132
TI  - Electro-acupuncture at Governor Vessel improves neurological function in rats
      with spinal cord injury.
AB  - OBJECTIVE: To determine the effects of electro-acupuncture (EA) at Governor
      Vessel (GV) on the locomotor function in spinal cord injury (SCI) rats and
      explore the underlying mechanism. METHODS: Thirtytwo male Sprague-Dawley rats
      were randomly divided into four groups namely: the sham group (with sham
      operation); the untreated group (without treatment after spinal cord impact); the
      EA-1 group [EA applied at Baihui (GV 20) and Fengfu (GV 16) after spinal cord
      impact] and the EA-2 group [with EA applied at Dazhui (GV 14) and Mingmen (GV 4)
      after spinal cord impact]. Real-time quantitative-polymerase chain reaction (RT
      PCR) and Western Blotting were used to assess changes in the mRNA and protein
      expression levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3
      (NT-3) at 7 weeks following EA administration. In addition, the Basso-Beattie
      Bresnahan (BBB) Locomotor Rating Scale was assessed at 1 day, 1 week, 3 weeks and
      7 weeks post-injury. RESULTS: The results showed that EA stimulation induced
      neuroprotective effects after SCI correlated with the up-regulation of BDNF and
      NT-3 (P<0.05). Furthermore, EA stimulation at GV 14 and GV 4 could significantly
      promote the recovery of locomotor function and this may be linked to the up
      regulation of BDNF and NT-3 (P<0.05). CONCLUSIONS: EA treatment applied at GV
      acupoints either within the injury site or adjacent undamaged regions near the
      brain can improve functional recovery, which may be correlated with the
      upregulation of BDNF and NT-3. In addition, it would be more effective to
      administer EA at GV 14 and GV 4 near the injury site of the SCI rats.

PMID- 28762133
TI  - Origins and Neurochemical Characteristics of Porcine Intervertebral Disc
      Sympathetic Innervation: a Preliminary Report.
AB  - Intervertebral disc diseases (IVDDs) form a group of a vertebral column disorders
      affecting a large number of people worldwide. It is estimated that approximately
      30% of individuals at the age of 35 and approximately 90% of individuals at the
      age of 60 and above will have some form of disc-affecting pathological changes
      leading to disc herniation, prolapse and degeneration as well as discogenic pain.
      Here, we aimed to establish the origins and neurochemical characteristics of
      porcine intervertebral disc sympathetic innervation involved in pain signalling
      in IVDD patients. Pigs were given an injection of the Ominipaque contrast agent
      and Fast Blue (FB) retrograde tracer into the L4-L5 intervertebral disc and
      euthanized at 2, 1, and 3 months post injection. Following euthanasia, bilateral
      sympathetic chain ganglia (SChG) Th13 to C1 were collected. The presence,
      distribution and neurochemical characteristics of retrogradely labelled SChG
      neurons were examined. The majority (88.8%) of all FB+ cells were found in the L3
      L5 SChG. Most FB+ neurons stained for dopamine beta hydroxylase (DBH); one-third
      to one-quarter stained for somatostatin (SOM), neuropeptide Y (NPY) or leu
      enkephalin (LENK); and only a few stained for galanin (GAL). Compared with the
      control, the greatest decline in neurochemical immunostaining was observed 2
      weeks post injection, and the lowest decline was noticed 1 month post injection.
      Our study, for the first time, provides insight into the complex patterns of
      intervertebral disc sympathetic innervation and suggests that the best time for
      neurochemical balance restoration therapy would be 1 month post-injury, when the
      neuronal concentration of all studied substances is close to the initial
      physiological level, thus providing favourable conditions for successful
      recovery.

PMID- 28762134
TI  - Detection of primary screw perforation in locking plate osteosynthesis of
      proximal humerus fracture by intra-operative 3D fluoroscopy.
AB  - PURPOSE: The purpose of this study was to identify the rate of primary screw
      perforations after osteosynthesis of proximal humerus fractures with intra
      operative 3D fluoroscopy and to analyse the rate of secondary screw perforations
      as well as complications, outcome, and revision surgeries after a minimum of 12
      months. MATERIALS AND METHODS: Thirty-three patients (20 female, 13 male, median
      age 67 years, range 35-85 years) with displaced proximal humerus fractures were
      included. After reduction and fixation, an intra-operative 3D fluoroscopy was
      performed to evaluate primary screw perforations (PS) and screws with "near
      perforation" (nPS). These screws were changed intra-operatively. Patients were
      followed-up for a minimum of 12 months. Clinical and radiological parameters,
      such as secondary screw perforation, secondary loss of reduction, or functional
      outcome, were investigated. RESULTS: In six patients (18.2%), humeral head screws
      were changed due to primary PS (n = 2) or nPS (n = 4) after the intra-operative
      3D fluoroscopy. Follow-up revealed an adapted constant score (%CMS) of 76.2%
      after a mean follow-up of 17.7 months. Two secondary screw perforations were
      observed (6%). Loss of reduction was observed in eight patients (24.2%).
      CONCLUSION: The intra-operative 3D reveals a high rate of primary screw
      perforations or near perforations. Immediate change of these screws may lead to a
      lower rate of secondary screw perforations and, therefore, reduce post-operative
      complications.

PMID- 28762135
TI  - Pharmacokinetic Optimization of Everolimus Dosing in Oncology: A Randomized
      Crossover Trial.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitor everolimus is used
      in the treatment of breast cancer, neuroendocrine tumors, and renal cancer. The
      approved 10 mg once-daily dose is associated with considerable adverse effects
      and it has been suggested that these are associated with the maximum
      concentration (C max) of everolimus. Twice-daily dosing might be an alternative
      strategy with improved tolerability; however, a direct pharmacokinetic comparison
      of 10 mg once-daily with 5 mg twice-daily dosing is lacking. METHODS: We
      performed a prospective, randomized, pharmacokinetic, crossover trial comparing
      everolimus 10 mg once daily with 5 mg twice daily. Patients received the first
      dose schedule for 2 weeks and then switched to the alternative regimen for 2
      weeks. Pharmacokinetic sampling was performed on days 14 and 28. RESULTS: Eleven
      patients were included in the study, of whom 10 were evaluable for
      pharmacokinetic analysis. On the 10 mg once-daily schedule, C max, minimum
      concentration (C min), and area under the concentration-time curve from time zero
      to 24 h (AUC24) were 61.5 ng/mL [mean percentage coefficient of variation (CV%)
      29.6], 9.6 ng/mL (CV% 35.0), and 435 ng h/mL (CV% 28.1), respectively. Switching
      to the 5 mg twice-daily schedule resulted in a reduction of C max to 40.3 ng/mL
      (CV% 46.6) (p = 0.013), while maintaining AUC24 at 436 ng h/mL (CV% 34.8) (p =
      0.952). C min increased to 13.7 ng/mL (CV% 53.9) (p = 0.018). The overall
      reduction in C max was 21.2 ng/mL, or 32.7%. The C max/C min ratio was reduced
      from 6.44 (CV% 36.2) to 3.18 (CV% 35.5) (p < 0.001). CONCLUSIONS: We demonstrated
      that switching from a once-daily to a twice-daily everolimus dose schedule
      reduces C max without negatively impacting C min or AUC24. These results merit
      further investigation of the twice-daily schedule in an effort to reduce
      everolimus toxicity while maintaining treatment efficacy. REGISTRATION: This
      trial was registered in the EurdaCT database (2014-004833-25) and the Netherlands
      Trial Registry (NTR4908).

PMID- 28762136
TI  - Predicting Cortisol Exposure from Paediatric Hydrocortisone Formulation Using a
      Semi-Mechanistic Pharmacokinetic Model Established in Healthy Adults.
AB  - BACKGROUND AND OBJECTIVE: Optimisation of hydrocortisone replacement therapy in
      children is challenging as there is currently no licensed formulation and dose in
      Europe for children under 6 years of age. In addition, hydrocortisone has non
      linear pharmacokinetics caused by saturable plasma protein binding. A paediatric
      hydrocortisone formulation, Infacort(r) oral hydrocortisone granules with taste
      masking, has therefore been developed. The objective of this study was to
      establish a population pharmacokinetic model based on studies in healthy adult
      volunteers to predict hydrocortisone exposure in paediatric patients with adrenal
      insufficiency. METHODS: Cortisol and binding protein concentrations were
      evaluated in the absence and presence of dexamethasone in healthy volunteers (n =
      30). Dexamethasone was used to suppress endogenous cortisol concentrations prior
      to and after single doses of 0.5, 2, 5 and 10 mg of Infacort(r) or 20 mg of
      Infacort(r)/hydrocortisone tablet/hydrocortisone intravenously. A plasma protein
      binding model was established using unbound and total cortisol concentrations,
      and sequentially integrated into the pharmacokinetic model. RESULTS: Both
      specific (non-linear) and non-specific (linear) protein binding were included in
      the cortisol binding model. A two-compartment disposition model with saturable
      absorption and constant endogenous cortisol baseline (Baseline cort,15.5 nmol/L)
      described the data accurately. The predicted cortisol exposure for a given dose
      varied considerably within a small body weight range in individuals weighing <20
      kg. CONCLUSIONS: Our semi-mechanistic population pharmacokinetic model for
      hydrocortisone captures the complex pharmacokinetics of hydrocortisone in a
      simplified but comprehensive framework. The predicted cortisol exposure indicated
      the importance of defining an accurate hydrocortisone dose to mimic physiological
      concentrations for neonates and infants weighing <20 kg. EudraCT number: 2013
      000260-28, 2013-000259-42.

PMID- 28762137
TI  - A Clinicopathologic Study of Head and Neck Malignant Peripheral Nerve Sheath
      Tumors.
AB  - Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are
      rare highly aggressive soft tissue sarcomas that show overlapping morphologic and
      immunophenotypic features with melanoma and other high grade sarcomas, resulting
      in diagnostic challenges, particularly in sporadic settings. Recent discoveries
      have implicated loss of function mutations in the polycomb repressive complex 2
      (PRC2) components, including EED or SUZ12 genes, as one of the leading
      pathogenetic mechanisms in high grade MPNST. MPNSTs with PRC2 loss are associated
      with complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3), which
      emerged as a reliable immunohistochemical marker in the diagnosis of sporadic and
      radiation induced MPNST. As the diagnosis of MPNST in the HN is particularly
      challenging to distinguish from melanoma and other sarcoma types, we carried out
      a clinicopathologic analysis on HN-MPNST patients managed at our institution over
      a 20-year period (1997-2016), using the latest diagnostic criteria including
      H3K27me3 staining and other molecular investigations. The overall survival of HN
      MPNST was compared with other HN soft tissue sarcomas. The diagnosis of HN-MPNST
      was confirmed in 13 patients (seven males and six females), with a mean age of 31
      years; with 3 (23%) patients being of pediatric age. The most common site was the
      neck soft tissue (77%). Two-thirds of patients (n = 9) had stigmata of NF1, three
      had prior radiotherapy and only one developed a de novo MPNST. All except one
      tumor (86%) tested showed loss of H3K27me3 expression, including all non-NF1
      patients. The 2 and 5-year DSS rates were 50 and 30%. The 2-year DFS rate was
      21%. Adverse predictors on DSS included adult age (p = 0.011), prior-history of
      RT (p = 0.003) and recurrence (p = 0.003). Compared to other molecularly
      confirmed subsets of HN sarcomas (Ewing and Ewing-like sarcoma, rhabdomyosarcoma
      and synovial sarcoma), HN-MPNST had the worst overall survival (p < 0.0001). We
      conclude that HN-MPNSTs are highly aggressive sarcomas associated with an
      unfavorable outcome and the utility of H3K27me3 IHC stains in the evaluation of
      MPNST is a reliable ancillary diagnostic adjunct.

PMID- 28762138
TI  - HRQOL using SF36 (generic specific) in liver cirrhosis.
AB  - Health-related quality of life (HRQOL) is influenced by the disease state,
      associated complications and their management. In patients with liver cirrhosis
      co-morbidity, severity of liver disease and their complications are likely to
      affect the QOL. The aim of the study was to determine the factors that are likely
      to influence the domains of HRQOL using SF-36 in patients with liver cirrhosis.
      For the study, 149 patients with liver cirrhosis were compared with age-gender
      matched healthy controls for physical and mental components of SF-36 score and
      the effects of age, co-morbidity severity of liver disease and complications of
      liver cirrhosis on HRQOL were assessed using the same questionnaire. Results of
      the study showed that except for body pain, all the patients had a significantly
      low individual and composite domain score (p-value <0.0001) compared to age
      gender matched controls. Patients below 45 years, Child-Turcotte-Pugh (CTP) C, a
      high model for end-stage liver disease (MELD) and higher rates of complication
      had low scores for body pain (KW p <0.005) and those above 55 years, for physical
      function (p <0.05). Both the physical components had a major impact on mental
      composite score (MCS) (KW p <0.05). Co-morbidity that included diabetes,
      hypertension and hypothyroid states in various combinations had no effect on SF
      36 scores while co-morbid conditions like musculoskeletal pain, arthralgia etc.
      affected physical domains (physical function, body pain and role physical) and
      physical component score (PCS) (KW p <0.01 to <0.0001). By linear regression,
      MELD had a direct and significant association with overall PCS and mental
      component score (MCS).

PMID- 28762139
TI  - Daclatasvir-Sofosbuvir for treatment of hepatitis C virus in patients with
      inherited bleeding disorders.

PMID- 28762140
TI  - The use of a transparent cap in sigmoidoscopy-A randomized controlled clinical
      trial on pain, time and success rate.
AB  - Trials on cap-assisted colonoscopy have shown a reduction in pain, faster
      intubation time and a higher success rate attributed to the use of the cap. No
      similar studies have been published on sigmoidoscopy even though it is a common
      procedure associated with significant pain. Our objective was to investigate
      whether the use of a transparent cap for sigmoidoscopy has an impact on pain,
      time or success rate. To mimic the tendencies of daily clinical practice, the
      trainee endoscopist performed the procedures, and no analgesics or sedatives were
      used. We conducted a randomized, controlled clinical trial with a parallel design
      consisting of two groups masked for the intervention. The primary endpoint was
      pain, recorded on a 100-mm visual analogue scale (VAS). Our results found cap
      assisted sigmoidoscopy to be significantly more painful than non-cap-assisted
      sigmoidoscopy (median VAS 50 vs. 38 mm; p = 0.047). We found no differences on
      time or success rate due to the cap. Our results suggest pain management, e.g.
      analgesics which is not routinely used for sigmoidoscopy, when a cap is used to
      gain therapeutic or diagnostic advantages. ClinicalTrials.gov Identifier:
      NCT02243930.

PMID- 28762142
TI  - Intracortical stiffness of mid-diaphysis femur bovine bone: lacunar-canalicular
      based homogenization numerical solutions and microhardness measurements.
AB  - Microscale lacunar-canalicular (L-C) porosity is a major contributor to
      intracortical bone stiffness variability. In this work, such variability is
      investigated experimentally using micro hardness indentation tests and
      numerically using a homogenization scheme. Cross sectional rings of cortical
      bones are cut from the middle tubular part of bovine femur long bone at mid
      diaphysis. A series of light microscopy images are taken along a line emanating
      from the cross-section center starting from the ring's interior (endosteum) ring
      surface toward the ring's exterior (periosteum) ring surface. For each image in
      the line, computer vision analysis of porosity is conducted employing an image
      segmentation methodology based on pulse coupled neural networks (PCNN) recently
      developed by the authors. Determined are size and shape of each of the lacunar
      canalicular (L-C) cortical micro constituents: lacunae, canaliculi, and Haversian
      canals. Consequently, it was possible to segment and quantify the geometrical
      attributes of all individual segmented pores leading to accurate determination of
      derived geometrical measures such as L-C cortical pores' total porosity (pore
      volume fraction), (elliptical) aspect ratio, orientation, location, and number of
      pores in secondary and primary osteons. Porosity was found to be unevenly (but
      linearly) distributed along the interior and exterior regions of the
      intracortical bone. The segmented L-C porosity data is passed to a numerical
      microscale-based homogenization scheme, also recently developed by the authors,
      that analyses a composite made up of lamella matrix punctuated by multi
      inclusions and returns corresponding values for longitudinal and transverse
      Young's modulus (matrix stiffness) for these micro-sized spatial locations.
      Hence, intracortical stiffness variability is numerically quantified using a
      combination of computer vision program and numerical homogenization code. These
      numerically found stiffness values of the homogenization solution are
      corroborated experimentally using microhardness indentation measurements taken at
      the same points that the digital images were taken along a radial distance
      emanating from the interior (endosteum) surface toward the bone's exterior
      (periosteum) surface. Good agreement was found between numerically calculated and
      indentation measured stiffness of Intracortical lamellae. Both indentation
      measurements and numerical solutions of matrix stiffness showed increasing linear
      trend of compressive longitudinal modulus (E11) values vs. radial position for
      both interior and exterior regions. In the interior (exterior) region of cortical
      bone, stiffness modulus values were found to range from 18.5 to 23.4 GPa (23 to
      26.0 GPa) with the aggregate stiffness of the cortical lamella in the exterior
      region being 12% stiffer than that in the interior region. In order to further
      validate these findings, experimental and FEM simulation of a mid-diaphysis bone
      ring under compression is employed. The FEM numerical deflections employed nine
      concentric regions across the thickness with graded stiffness values based on the
      digital segmentation and homogenization scheme. Bone ring deflections are found
      to agree well with measured deformations of the compression bone ring.

PMID- 28762141
TI  - Anti-fibronectin aptamers improve the colonization of chitosan films modified
      with D-(+) Raffinose by murine osteoblastic cells.
AB  - The aim of the present study was to investigate how the enrichment of chitosan
      films with anti-fibronectin aptamers could enhance scaffold colonization by
      osteoblasts, by improving their adhesion and accelerating their proliferation.
      Chitosan discs were enriched with excess of anti-fibronectin aptamer. Aptamer
      adsorption on chitosan was monitored by measuring aptamer concentration in the
      supernatant by spectrophotometry, as well as its release, while functionalization
      was confirmed by labelling aptamers with a DNA intercalating dye. Chitosan
      samples were then characterized morphologically with atomic force microscopy and
      physically with contact angle measurement. Chitosan enrichment with fibronectin
      was then investigated by immunofluorescence and Bradford assay. 2% chitosan discs
      were then enriched with increasing doses of aptamers and used as culture
      substrates for MC3T3-E1 cells. Cell growth was monitored by optical microscopy,
      while cell viability and metabolic activity were assessed by chemiluminescence
      and by Resazurin Sodium Salt assay. Cell morphology was investigated by
      cytofluorescence and by scanning electron microscopy. Chitosan films efficiently
      bound and retained aptamers. Aptamers did not affect the amount of adsorbed
      fibronectin, but affected osteoblasts behavior. Cell growth was proportional to
      the amount of aptamer used for the functionalization, as well as aptamers
      influenced cell morphology and their adhesion to the substrate. Our results
      demonstrate that the enrichment of chitosan films with aptamers could selectively
      improve osteoblasts behavior. Furthermore, our results support further
      investigation of this type of functionalization as a suitable modification to
      ameliorate the biocompatibility of biomaterial for hard tissue engineering
      applications.

PMID- 28762143
TI  - Pharmaceutical Interventions for Diabetes Prevention in Patients at Risk.
AB  - With the rising incidence and prevalence rates of type 2 diabetes globally, it is
      imperative that diabetes prevention strategies are implemented to stem the flow
      of new cases. Successful interventions include both lifestyle modification and
      pharmaceutical agents, and large, multicentre, randomised, controlled studies in
      different populations have identified the benefits of both. However, translating
      positive trial outcomes to the real world is particularly challenging, as
      lifestyle interventions require regular reinforcement from healthcare
      professionals to be maintained. Pharmaceutical therapies may therefore play an
      adjunctive role in combination with lifestyle to prevent diabetes. Population
      based strategies are also necessary to reduce sedentary behaviour and obesity.
      Well-established glucose-lowering therapies such as metformin, sulphonylureas,
      thiazolidinediones and insulin and newer agents such as incretin therapies and
      sodium glucose co-transporter 2 inhibitors have all been investigated in
      randomised controlled trials for diabetes prevention with varying success. Non
      glucose-lowering therapies such as orlistat and renin angiotensin system blockers
      can prevent diabetes, whereas statins are associated with slightly increased
      risk. Diabetes prevention strategies should carefully consider the use of these
      agents according to individual patient circumstances and phenotypic profile.

PMID- 28762144
TI  - Assessment of aluminum bioavailability in alum sludge for agricultural
      utilization.
AB  - Inorganic aluminum ions, [Al(H2O)6]3+, [Al(OH)(H2O)5]2+, and [Al(OH)2(H2O)4]+,
      are toxic to a number of crops. The aim of this study was to estimate the danger
      of soil contamination of bioavailable aluminum and heavy metals forms because of
      alum sludge which was a by-product of water, and wastewater treatment technology
      using aluminum coagulant is introduced into the soil. Aluminum and selected heavy
      metal fractionation was carried out in the post-coagulation sludge collected at a
      water treatment plant (where aluminum was used as a coagulant), fermented sewage
      sludge at a municipal wastewater treatment plant (which did not apply aluminum
      coagulant), and soil from water treatment plant as well as the mixtures of sludge
      and soil. It has been found that post-coagulation sludge used as natural
      fertilizer is a secondary source of bioavailable aluminum, especially when
      aluminum coagulants are used during water and wastewater treatment. The
      evaluation of applicability of the sludge to very weak acidic and acidic
      agricultural soils was carried out. The authors shall debate the question
      whether, in this case, the Regulation of EU and Polish Government on sewage
      sludge should also take the bioavailable aluminum into account and add to the
      list of the elements whose allowable contents are limited.

PMID- 28762145
TI  - Modeling of Cr contamination in the agricultural lands of three villages near the
      leather industry in Kasur, Pakistan, using statistical and GIS techniques.
AB  - Kasur is one of the hubs of leather industry in the Punjab, Pakistan, where
      chrome tanning method of leather processing is extensively being used. Chromium
      (Cr) accumulation levels in the irrigation water, soil, and seasonal vegetables
      were studied in three villages located in the vicinity of wastewater treatment
      plant and solid waste dumping site operated by the Kasur Tanneries Waste
      Management Agency (KTWMA). The data was interpreted using analysis of variance
      (ANOVA), clustering analysis (CA), and principal component analysis (PCA).
      Interpolated surface maps for Cr were generated using the actual data obtained
      for the 30 sampling sites in each of the three villages for irrigation water,
      soil, and seasonal vegetables. The level of contamination in the three villages
      was directly proportional to their distance from KTWMA wastewater treatment plant
      and the direction of water runoff. The highest level of Cr contamination in soil
      (mg kg-1) was observed at Faqeeria Wala (37.67), intermediate at Dollay Wala
      (30.33), and the least in Maan (25.16). A gradational variation in Cr
      accumulation was observed in the three villages from contaminated wastewater
      having the least contamination level (2.02-4.40 mg L-1), to soil (25.16-37.67 mg
      kg-1), and ultimately in the seasonal vegetable crops (156.67-248.33 mg kg-1)
      cultivated in the region, having the highest level of Cr contamination above the
      permissible limit. The model used not only predicted the current situation of Cr
      contamination in the three villages but also indicated the trend of magnification
      of Cr contamination from irrigation water to soil and to the base of the food
      chain. Among the multiple causes of Cr contamination of vegetables, soil
      irrigation with contaminated groundwater was observed to be the dominant one.

PMID- 28762146
TI  - The influence of chemical protection on the content of heavy metals in wheat
      (Triticum aestivum L.) growing on the soil enriched with granular sludge.
AB  - The presence of heavy metals in Triticum aestivum L. growing on the soil enriched
      with granular sludge after chemical protection was observed. The five variants of
      treatments using herbicide (Chwastox Turbo 340SL) and four fungicides (Topsin M
      500SC, Amistar 250SC, Artea 330EC, and Falcon 460EC) were performed. On control
      and experimental plots, the concentration of Ni, Pb, Cr, and Cu in wheat leaves
      were in the range 0.32-0.99, 0.92-1.57, 0.89-6.31, and 7.08-12.59 mg/kg and in
      grains 0.03 to 0.11, 0.14-0.25, 0.11-0.76, and 1.06-1.46 mg/kg, respectively. The
      concentration of Pb in grain protected by MCPA and 2,4-D with thiophanate-methyl
      and azoxystrobin was higher than the maximum levels of 0.20 mg/kg D.M. The
      bioconcentration factor (BCF) differed and depended on chemical protection. The
      highest value of BCF was achieved for Cd. The statistical analysis showed a
      significant correlation between concentration of metals and quality parameters of
      wheat. One observed significant negative correlations between Ni/Zeleny
      sedimentation value (r = -0.51) and between Pb/starch content (r = -0.57).
      Positive correlations were observed between Cd/yield, the number of
      grains/ergosterol concentration (respectively, r = 0.41, r = 0.55, r = 0.56), and
      Zn/thousand grain weight (r = 0.50) at a p <= 0.05.

PMID- 28762147
TI  - PAHs in water and surface sediments from Douro River estuary and Porto Atlantic
      coast (Portugal)-impacts on human health.
AB  - This study investigated the presence of 16 priority polycyclic aromatic compounds
      (PAHs) in waters from the Douro River estuary and nearby Atlantic seacoast, which
      both bath the Porto metropolis. In the area, there is an oil refinery, an
      important harbour, an intense maritime traffic, small marinas and highly
      inhabited cities. For the analysis of PAHs, water samples were taken from four
      sampling sites, at six different times of the year (2011), and extracted by solid
      phase extraction (dissolved fraction) and by ultrasound technique (suspended
      fraction), before their quantification by gas chromatography-mass spectrometry.
      Results not only proved the ubiquitous distribution of all analysed PAHs in the
      present habitat, but also that their global amounts (?16PAHs) were extremely high
      at all sampling sites. Their average concentrations attained ~ 55 ng/L and ~ 52
      MUg/g dry weight (dw), respectively, in water and surface sediments. Accordingly,
      the surveyed area was classified as highly polluted by these organics and so, in
      view of the concentrations, mutagenic/carcinogenic responses in both humans and
      aquatic animals are possible to occur. The percentages of carcinogenic PAHs for
      humans (group 1) dissolved in water and in surface sediments were ca. 5 and 6%,
      respectively. These results are the first reported in the area and can be used as
      a baseline for future control of the PAHs levels locally while serving the
      building of global scenarios of PAHs pollution in Europe. Graphical abstract
      Percentage of PAHs, from different categories acordingly to WHO (2016), in both
      surface sediments and surface waters from Douro River estuary and Porto Atlantic
      seacoast; group 1 - carcinogenic, group 2A - probably carcinogenic, group 2B -
      possibly carcinogenic, and group 3 - not classifiable as carcinogenic to humans.

PMID- 28762148
TI  - Real Stress Reactions in Simulation: Vignettes from Extended Mass-Casualty
      Simulations.

PMID- 28762149
TI  - CORR Insights(r): Are There Differences in Gait Mechanics in Patients With A
      Fixed Versus Mobile Bearing Total Ankle Arthroplasty? A Randomized Trial.

PMID- 28762150
TI  - Editorial: The Opioid Epidemic and Orthopaedic Surgery-No Pain, Who Gains?

PMID- 28762151
TI  - A preliminary investigation of short-term cytokine  expression in gingival
      crevicular fluid secondary to high-level orthodontic forces and the associated
      root resorption: case series analytical study.
AB  - BACKGROUND: Orthodontically induced iatrogenic root resorption (OIIRR) is an
      unavoidable inflammatory process. Several factors claimed to be related to the
      severity of OIIRR. Orthodontic forces cause micro-trauma to the periodontal
      ligament and activate a cascade of cellular events associated with local
      periodontal inflammation. The purpose of this split-mouth study were (1) to
      investigate the changes in cytokine profile in the gingival crevicular fluid
      (GCF) secondary to heavy orthodontic forces and (2) to compare the cytokine
      expression between participants showing high and low root resorption. METHODS:
      Eight participants requiring maxillary first premolar extractions involved in
      this study. The teeth on the tested side (TS) received 225 g of controlled buccal
      tipping force for 28 days, while the contralateral teeth act as a control (CS).
      GCF was collected from both TS and CS teeth at 0 h (prior to application of
      force) and 3 h, 1 day, 3 days, 7 days and 28 days after the application of force,
      and analysed with multiplex bead immunoassay to determine the cytokine levels.
      RESULTS: Statistically significant temporal increase was found in the TS teeth
      for tumour necrosis factor alpha (TNF-alpha) at 3 h and 28 days (p = 0.01).
      Interleukin 7 (IL-7) significantly peaked at the 28th day. Comparing cytokine
      profile for participants with high and low root resorption (>0.35 and <0.15 mm3,
      respectively), the levels of GM-CSF was significantly greater in low root
      resorption cases (p < 0.05). The amounts of root resorption which craters on
      mesial, distal surfaces and middle third region were significant in the TS teeth
      (p < 0.05). CONCLUSIONS: IL-7 and TNF-alpha (pro-resorptive cytokine) increased
      significantly secondary to a high-level of orthodontic force application.
      Significantly high levels of granulocyte macrophage colony-stimulating factor
      (anti-resorptive cytokine) were detected in mild root resorption cases secondary
      to high-level orthodontic force application. A future long-term randomised
      clinical trial with larger sample taking in consideration gender, age and growth
      pattern distribution would be recommended.

PMID- 28762152
TI  - Quantitative analysis of the relationship between maxillary incisors and the
      incisive canal by cone-beam computed tomography in an adult Japanese population.
AB  - BACKGROUND: In setting goals for orthodontic treatment, determining the
      morphologies of the alveolar bone and maxillary incisor root is important for
      avoiding root resorption, dehiscence, and fenestration. This study aimed to
      analyze the configurational relationships among maxillary incisors, the alveolar
      border, and the incisive canal by cone-beam computed tomography (CBCT). METHODS:
      Cone-beam CT images of 93 orthodontic patients were evaluated for length of the
      incisive canal (L); angles between the palatal plane and the maxillary alveolar
      border (theta1), the incisive canal (theta2), and maxillary incisor (theta3);
      distance from the left maxillary incisor to the incisive canal (D); and cross
      sectional areas of the incisive canal (CSAs) at three vertical levels. Comparison
      of variables between male and female patients was performed with the two-sample t
      test. Correlations between parameters were examined by Pearson's correlation
      analysis and Bonferroni correction for multiple comparisons. RESULTS: Male
      patients exhibited significantly greater values of L than female patients. There
      were significant positive correlations between theta1 and theta2, theta2 and
      theta3, and theta3 and theta1. While the value of D was the lowest at the oral
      opening, that of the cross-sectional area of the incisive canal (CSA) was the
      greatest at the incisal root apex. CONCLUSIONS: This study demonstrated that the
      incisive canal had large inter-individual variability, and the proximity between
      the incisive canal and the incisal root could not be precisely predicted by the
      conventional cephalograms. Therefore, pre-treatment CBCT examination should be
      recommended when a large amount of maxillary anterior retraction and/or intrusion
      is planned in orthodontic diagnosis.

PMID- 28762153
TI  - A retrospective cephalometric study on upper airway spaces in different facial
      types.
AB  - BACKGROUND: Craniofacial growth pattern has been correlated with variations in
      size of the upper airway spaces. The objective of this study was to evaluate the
      nasopharyngeal, oropharyngeal, and hypopharyngeal airway spaces variations
      according to the craniofacial growth pattern, by comparing brachyfacial,
      mesofacial, and dolichofacial in Angle Class I individuals. METHODS: To measure
      the spaces, 45 lateral teleradiographs were used and divided into 3 groups per
      the craniofacial growth pattern, determined by the Tweed cephalometry angular
      measurements: FMA and Y-axis. To evaluate the airways, sleep apnea cephalometry
      was used, containing 28 points that compose 14 factors. Three groups were
      compared relative to each of the 14 sleep apnea cephalometry measurements.
      Adherence test to the normal curve was performed. For the non-normally
      distributed data-measurement of the inferior pharyngeal space-the Kruskal-Wallis
      test was used for comparison between the groups. For the remaining data, the
      distribution was normal and ANOVA test was used. RESULTS: Statistically
      significant difference was verified among the groups for the measurement of the
      median posterior-palatal space, with the difference being pointed out by the post
      hoc test between the brachyfacial and dolichofacial groups. For the other
      measurements, there was no statistically significant difference. CONCLUSIONS: It
      could be concluded that there was difference in the median posterior-palatal
      space measurement, in the oropharynx region, which was reduced for individuals
      with a dolichofacial pattern.

PMID- 28762154
TI  - The Aortic Bifurcation Angle as a Factor in Application of the Outback for
      Femoropopliteal Lesions in Ipsilateral Versus Contralateral Approaches.
AB  - PURPOSE: To assess the technical success of the Outback reentry device in
      contralateral versus ipsilateral approaches for femoropopliteal arterial
      occlusion. MATERIALS AND METHODS: A retrospective review of patients treated for
      critical limb ischemia (CLI) using the Outback between January 2013 and July 2016
      was performed. Age, gender, length and site of the occlusion, approach site,
      aortic bifurcation angle, and reentry site were recorded. Calcification score was
      assigned at both aortic bifurcation and reentry site. Technical success was
      assessed. RESULTS: During the study period, a total of 1300 endovascular
      procedures were performed on 489 patients for CLI. The Outback was applied on 50
      femoropopliteal chronic total occlusions. Thirty-nine contralateral and 11
      ipsilateral antegrade femoral were accessed. The device was used successfully in
      41 patients (82%). There were nine failures, all in the contralateral approach
      group. Six due to inability to deliver the device due to acute aortic bifurcation
      angle and three due to failure to achieve luminal reentry. Procedural success was
      significantly affected by the aortic bifurcation angle (p = 0.013). CONCLUSION:
      The Outback has high technical success rates in treatment of femoropopliteal
      occlusion, when applied from either an ipsi- or contralateral approach. When
      applied in contralateral access, acute aortic bifurcation angle predicts
      procedural failure.

PMID- 28762155
TI  - Spatial knowledge during skilled action sequencing: Hierarchical versus
      nonhierarchical representations.
AB  - Typists can type 4 to 5 keystrokes per second at around 95% accuracy, yet they
      appear to have poor declarative knowledge of key locations. Logan and Crump
      (2011, Psychology of Learning and Motivation, Vol. 54, pp. 1-27) accounted for
      this paradox by proposing that typing is hierarchically organized into two loops,
      with an outer loop that transforms sentences into words and passes each word, one
      at a time, to an inner loop that transforms each word into its constituent
      keystrokes; however, the nature of the inner loop's spatial knowledge is not well
      understood. Key locations may be learned through the experiences of locating and
      traversing between keys. In daily life, people tend to type structured language,
      and, as a consequence, certain keys and key-to-key transitions are experienced
      more frequently than others. Here, we asked whether or not this knowledge is
      structured hierarchically. For example, knowledge of key locations may be nested
      within representations of words, or the inner loop may rely on knowledge that is
      independent from higher level structures. To test this, we had people type
      English, English-like, and random strings during normal, partially occluded, and
      occluded typing. In both partially occluded and occluded typing, error rates were
      higher while typing random strings compared to English and English-like strings,
      whereas there was no difference in error rates between English and English-like
      strings. This suggests that typists' spatial knowledge of the keyboard is not
      driven by hierarchical word-level representations, but instead is likely driven
      by a collection of individual processes, such as knowledge of the sequential
      structure of language acquired by typing more frequently occurring letters.

PMID- 28762156
TI  - Quantifying sources of bias in longitudinal data linkage studies of child abuse
      and neglect: measuring impact of outcome specification, linkage error, and
      partial cohort follow-up.
AB  - BACKGROUND: Health informatics projects combining statewide birth populations
      with child welfare records have emerged as a valuable approach to conducting
      longitudinal research of child maltreatment. The potential bias resulting from
      linkage misspecification, partial cohort follow-up, and outcome misclassification
      in these studies has been largely unexplored. This study integrated
      epidemiological survey and novel administrative data sources to establish the
      Alaska Longitudinal Child Abuse and Neglect Linkage (ALCANLink) project. Using
      these data we evaluated and quantified the impact of non-linkage misspecification
      and single source maltreatment ascertainment use on reported maltreatment risk
      and effect estimates. METHODS: The ALCANLink project integrates the 2009-2011
      Alaska Pregnancy Risk Assessment Monitoring System (PRAMS) sample with multiple
      administrative databases through 2014, including one novel administrative source
      to track out-of-state emigration. For this project we limited our analysis to the
      2009 PRAMS sample. We report on the impact of linkage quality, cohort follow-up,
      and multisource outcome ascertainment on the incidence proportion of reported
      maltreatment before age 6 and hazard ratios of selected characteristics that are
      often available in birth cohort linkage studies of maltreatment. RESULTS: Failure
      to account for out-of-state emigration biased the incidence proportion by 12%
      (from 28.3%w to 25.2%w), and the hazard ratio (HR) by as much as 33% for some
      risk factors. Overly restrictive linkage parameters biased the incidence
      proportion downwards by 43% and the HR by as much as 27% for some factors. Multi
      source linkages, on the other hand, were of little benefit for improving reported
      maltreatment ascertainment. CONCLUSION: Using the ALCANLink data which included a
      novel administrative data source, we were able to observe and quantify bias to
      both the incidence proportion and HR in a birth cohort linkage study of reported
      child maltreatment. Failure to account for out-of-state emigration and low
      quality linkage methods may induce bias in longitudinal data linkage studies of
      child maltreatment which other researchers should be aware of. In this study
      multi-agency linkage did not lead to substantial increased detection of reported
      maltreatment. The ALCANLink methodology may be a practical approach for other
      states interested in developing longitudinal birth cohort linkage studies of
      maltreatment that requires limited resources to implement, provides comprehensive
      data elements, and can facilitate comparability between studies.

PMID- 28762158
TI  - The validity and accuracy of MRI arthrogram in the assessment of painful
      articular disorders of the hip.
AB  - The assessment of a patient with chronic hip pain can be challenging. The
      differential diagnosis of intra-articular pathology causing hip pain can be
      diverse. These includes conditions such as osteoarthritis, fracture, and
      avascular necrosis, synovitis, loose bodies, labral tears, articular pathology
      and, femoro-acetabular impingement. Magnetic resonance imaging (MRI) arthrography
      of the hip has been widely used now for diagnosis of articular pathology of the
      hip. A retrospective analysis of 113 patients who had MRI arthrogram and who
      underwent hip arthroscopy was included in the study. The MRI arthrogram was
      performed using gadolinium injection and reported by a single radiologist. The
      findings were then compared to that found on arthroscopy. The sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV),
      accuracy and 95% confidence interval were calculated for each pathology. Labral
      tear-sensitivity 84% (74.3-90.5), specificity 64% (40.7-82.8), PPV 91% (82.1
      95.8), NPV 48% (29.5-67.5), accuracy 80%. Delamination -sensitivity 7% (0.8
      22.1), specificity 98% (91.6-99.7), PPV 50% (6.8-93.2), NPV 74% (65.1-82.2) and
      accuracy 39%. Chondral changes-sensitivity 25% (13.3-38.9), specificity 83% (71.3
      91.1), PPV 52% (30.6-73.2), NPV 59% (48.0-69.2) and accuracy 58%. Femoro
      acetabular impingement (CAM deformity)-sensitivity 34% (19.6-51.4), specificity
      83% (72.2-90.4), PPV 50% (29.9-70.1), NPV 71% (60.6-80.5) and accuracy 66%.
      Synovitis-sensitivity 11% (2.3-28.2), specificity 99% (93.6-100), PPV 75% (19.4
      99.4), NPV 77% (68.1-84.6) and accuracy 77%. Our study conclusions are MRI
      arthrogram is a useful investigation tool in detecting labral tears, it is also
      helpful in the diagnosis of femoro-acetabular impingement. However, when it comes
      to the diagnosis of chondral changes, defects and cartilage delamination, the
      sensitivity and accuracy are low.

PMID- 28762157
TI  - Risk markers for fatal and non-fatal prescription drug overdose: a meta-analysis.
AB  - BACKGROUND: Drug overdose is a public health crisis in the United States, due in
      part to the unintended consequences of increases in prescribing of opioid
      analgesics. Many clinicians evaluate risk markers for opioid-related harms when
      prescribing opioids for chronic pain; however, more data on predictive risk
      markers are needed. Risk markers are attributes (modifiable and non-modifiable)
      that are associated with increased probability of an outcome. This review aims to
      identify risk markers associated with fatal and non-fatal prescription drug
      overdose by synthesizing findings in the existing peer-reviewed and grey
      literature. Eligible cohort, case-control, cross-sectional, and case-cohort
      studies were reviewed and data were extracted for qualitative and quantitative
      synthesis. FINDINGS: Summary odds ratios (SOR) were estimated from 29 studies for
      six risk markers: sex, age, race, psychiatric disorders, substance use disorder
      (SUD), and urban/rural residence. Heterogeneity was assessed and effect estimates
      were stratified by study characteristics. Of the six risk markers identified, SUD
      had the strongest association with drug overdose death (SOR = 5.24, 95%
      confidence interval (CI) = 3.53 - 7.76), followed by psychiatric disorders (SOR =
      3.94, 95% CI = 3.09 - 5.01), white race (SOR = 2.28, 95% CI = 1.93 - 2.70), the
      35-44 year age group relative to the 25-34 year reference group (SOR = 1.52, 95%
      CI = 1.31 - 1.76), and male sex (SOR = 1.33, 95% CI = 1.17 - 1.51). CONCLUSIONS:
      This review highlights fatal and non-fatal prescription drug risk markers most
      frequently assessed in peer-reviewed and grey literature. There is a need to
      better understand modifiable risk markers and underlying reasons for drug misuse
      in order to inform interventions that may prevent future drug overdoses.

PMID- 28762159
TI  - Accurate Autism Screening at the 18-Month Well-Child Visit Requires Different
      Strategies than at 24 Months.
AB  - Accuracy of autism screening using M-CHAT plus the follow-up interview (M-CHAT/F)
      for children screened positive at 18-months was compared to screening at 24
      months. Formal ASD testing was criterion for a community sample of M-CHAT
      positive children (n = 98), positive predictive value (PPV) was 0.40 for the M
      CHAT and 0.58 for the M-CHAT/F. MCHAT/F PPV was 0.69 among children 20+ months
      compared to 0.36 for <20 months. Multivariate analyses incorporating data from
      the Ages and Stages Questionnaire, MacArthur-Bates Communicative Development
      Inventory, M-CHAT and M-CHAT/F results, and M-CHAT items suggest language
      variables carry greatest relative importance in contributing to an age-based
      algorithm with potential to improve PPV for toddlers <20 months to the same level
      as observed in older toddlers.

PMID- 28762160
TI  - Parental Outcomes Following Participation in Cognitive Behavior Therapy for
      Children with Autism Spectrum Disorder.
AB  - Children with autism spectrum disorder (ASD) benefit from parent involvement in
      their therapy, and there is evidence that this involvement may improve parent
      functioning as well. We examined changes in parent mental health, parenting, and
      expressed emotion, following participation in a randomized controlled trial of
      cognitive behavior therapy for 57 children with ASD. Post-intervention,
      improvements occurred in the treatment group in parent depression and emotion
      regulation, compared to waitlisted parents. Treatment effects also occurred
      across all parents in depression, emotion regulation, perceptions of their
      children and mindful parenting. Though preliminary, these results have
      implications for intervention development and evaluation by focusing on parent
      outcomes in child treatment.

PMID- 28762161
TI  - Muscarinic receptors in adrenal chromaffin cells: physiological role and
      regulation of ion channels.
AB  - Adrenal medullary chromaffin cells in mammals are innervated by sympathetic
      preganglionic nerve fibers, as are sympathetic ganglion neurons. Acetylcholine in
      the ganglion neurons is well established as mediating fast and slow excitatory
      postsynaptic potentials through nicotinic and muscarinic acetylcholine receptors
      (AChRs), respectively. The role of muscarinic AChRs during neuronal transmission
      in chromaffin cells varies among different mammals. Furthermore, the ion channel
      mechanisms associated with the muscarinic AChR-mediated increase in excitability
      of chromaffin cells are complicated and different from the excitation of ganglion
      neurons, which has been ascribed to the inhibition of M-type K+ channels. In this
      review, we focus on muscarinic receptor-mediated excitation in rodent and guinea
      pig chromaffin cells, in particular, on the role of muscarinic receptors in
      neuronal transmission, the muscarinic receptor subtypes involved in excitation
      and secretion, and the muscarinic regulation of ion channels including TWIK
      related acid-sensitive K+ channels. Finally, we discuss prospectively the future
      of muscarinic receptor research in adrenal chromaffin cells.

PMID- 28762162
TI  - Effect of acute treadmill exercise on cisplatin-induced muscle atrophy in the
      mouse.
AB  - Cisplatin, a platinum-based anti-cancer drug, is one of the most effective broad
      spectrum anti-cancer agents used against various cancers. It has been recently
      suggested that low skeletal muscle mass is predictive of mortality in patients
      with cancer. Although several molecules produced by the actual tumor itself
      contribute to skeletal muscle impairment, we recently suggested that the
      administration of cisplatin could increase levels of muscle RING finger-1 (MuRF1)
      and atrogin-1, possibly leading to muscle atrophy in the mouse. Exercise is an
      important factor that induces muscle protein synthesis and muscle hypertrophy by
      enhancing the positive effects of the Akt/mTOR/p70S6 kinase pathway. In the
      present study, we therefore investigated the effect of treadmill exercise on
      cisplatin-induced muscle atrophy. C57BL/6J mice were treated with cisplatin (3
      mg/kg, i.p.) or saline for four consecutive days. On day 4, the quadriceps and
      gastrocnemius muscles were isolated from the mice. The animals in the treadmill
      exercise groups were forced to run on a motorized treadmill for 20 min once a day
      for 9 days. In addition to muscle mass, the decrease in myofiber diameter
      associated with cisplatin administration was significantly restored by treadmill
      exercise. This exercise also significantly attenuated cisplatin-induced
      upregulation of MuRF1 and atrogin-1 in quadriceps and gastrocnemius muscle. The
      decreased Akt, p70S6 kinase, and Foxo3a phosphorylation observed with cisplatin
      treatment was significantly recovered by treadmill exercise in both the muscles.
      In the present study, myostatin (Mstn) gene expression, upregulated by cisplatin
      administration, was also attenuated by treadmill exercise. These findings suggest
      that treadmill exercise could attenuate cisplatin-induced muscle atrophy, at
      least partially, and could improve prognosis.

PMID- 28762164
TI  - Erratum to: Critically Underdeveloped Left Heart Morphology Associated with
      Prematurity and Low Birth Weight: Conditional Staged Rehabilitation Towards
      Biventricular Repair and Time-Related Growth of Left Heart Structures.

PMID- 28762163
TI  - Polycystin 2-dependent cardio-protective mechanisms revealed by cardiac stress.
AB  - Although autosomal dominant polycystic kidney disease (ADPKD) is characterized by
      the development of multiple kidney cysts, the most frequent cause of death in
      ADPKD patients is cardiovascular disease. ADPKD is linked to mutations in PKD1 or
      pkd2, the genes that encode for the proteins polycystin 1 and polycystin 2 (PC1
      and PC2, respectively). The cardiovascular complications have been assumed to be
      a consequence of renal hypertension and activation of
      renin/angiotensin/aldosterone (RAAS) pathway. However, the expression of PC1 and
      PC2 in cardiac tissue suggests additional direct effects of these proteins on
      cardiac function. We previously reported that zebrafish lacking PC2 develop heart
      failure, and that heterozygous Pkd2+/- mice are hypersensitive to acute beta
      adrenergic receptor (betaAR) stimulation. Here, we investigate the effect of
      cardiac stress (prolonged continuous betaAR stimulus) on Pkd2+/- mice. After
      betaAR stimulation for 7 days, wild-type (WT) mice had increased left ventricular
      mass and natriuretic peptide (ANP and BNP) mRNA levels. The WT mice also had
      upregulated levels of PC2 and chromogranin B (CGB, an upstream regulator of BNP).
      Conversely, Pkd2+/- mice had increased left ventricular mass, but natriuretic
      peptide and CGB expression levels remained constant. Reversal of the increased
      cardiac mass was observed in WT mice 3 days after cessation of the betaAR
      stimulation, but not in Pkd2+/- mice. We suggest that cardiac stress leads to
      upregulation of the PC2-CGB-BNP signaling axis, and this pathway regulates the
      production of cardio-protective natriuretic peptides. The lack of a PC2-dependent
      cardio-protective function may contribute to the severity of cardiac dysfunction
      in Pkd2+/- mice and in ADPKD patients.

PMID- 28762165
TI  - The Mid-term Results of Mitral Valve Repair for Isolated Mitral Regurgitation in
      Infancy and Childhood.
AB  - The objective of this study was to assess the mid-term results of mitral valve
      (MV) repair in infancy and childhood with isolated mitral regurgitation (MR).
      From January 2005 to January 2016, 40 consecutive patients with isolated MR
      underwent MV repair in Fuwai Hospital, Beijing, China. Patients' clinical data
      were analyzed retrospectively. Mean age at operation was 13 +/- 5 (6-24) months
      and 22 patients (55%) were younger than 1 year. Mean weight at operation was 8.5
      +/- 1.9 (4.2-13) kg and 34 patients (85%) were lighter than 10 kg. All patients
      presented moderate or greater MR. After MV repair, all patients had mild MR or
      none, while two patients underwent re-repair immediately when TEE showed moderate
      MR. Mean left atrial diameter decreased from 28.0 +/- 6.5 to 20.7 +/- 4.8 mm and
      mean left ventricular end-diastolic diameter decreased from 38.6 +/- 7.0 to 30.2
      +/- 4.9 mm (p < 0.001 for both). There was no early death. Clinical follow-up was
      conducted in 37 patients over an average period of 49 +/- 31 (20-134) months.
      Follow-up echocardiography showed that one patient had severe MR who underwent
      redo repair 14 months after operation, one patient had moderate to severe MR, and
      three patients had moderate MR. Overall freedom from moderate or greater MR was
      96.3 +/- 3.6%, 91.9 +/- 5.5%, and 83.6 +/- 9.4% at 2, 5, and 10 years,
      respectively. The early and mid-term results of MV repair in pediatric patients
      with isolated MR were satisfactory. In majority of patients, less complex
      surgical repair techniques were utilized, namely annuloplasty or
      commissuroplasty. The combination of various repair methods in complex patients
      could achieve excellent outcome.

PMID- 28762166
TI  - Accuracy and Specific Value of Cardiovascular 3D-Models in Pediatric CT
      Angiography.
AB  - Computed tomography (CT)-angiography is routinely performed prior to catheter
      based and surgical treatment in congenital heart disease. To date, little is
      known about the accuracy and advantage of different 3D-reconstructions in CT
      data. Exact anatomical information is crucial. We analyzed 35 consecutive CT
      angiographies of infants with congenital heart disease. All datasets are
      reconstructed three-dimensionally using volume rendering technique (VRT) and
      threshold-based segmentation (stereolithographic model, STL). Additionally, the
      two-dimensional maximum intensity projection (MIP) reconstructs two-dimensional
      data. In each dataset and resulting image, measurements of vascular diameters for
      four different vessels were estimated and compared to the reference standard,
      measured via multiplanar reformation (MPR). The resulting measurements obtained
      via the STL-images, MIP-images, and the VRT-images were compared with the
      reference standard. There was a significant difference (p < 0.05) between
      measurements. The mean difference was 0.0 for STL-images, -0.1 for MIP-images,
      and -0.3 for VRT-images. The range of the differences was -0.7 to 1.0 mm for STL
      images, -0.6 to 0.5 mm for MIP-images and -1.1 to 0.7 mm for VRT-images. There
      was an excellent correlation between the STL-, MIP-, VRT-measurements, and the
      reference standard. Inter-reader reliability was excellent (p < 0.01). STL-models
      of cardiovascular structures are more accurate than the traditional VRT-models.
      Additionally, they can be standardized and are reproducible.

PMID- 28762168
TI  - The Role of Computed Tomography in the Diagnosis of Necrotizing Soft Tissue
      Infections.
AB  - BACKGROUND: The exact role of IV contrast-enhanced computed tomography (CT) in
      the diagnosis of necrotizing soft tissue infections (NSTIs) has not yet been
      established. We aimed to explore the role of CT in patients with clinical
      suspicion of NSTI and assess its sensitivity and specificity for NSTI. METHODS:
      The medical records of patients admitted between 2009 and 2016, who received IV
      contrast-enhanced CT to rule out NSTI, were reviewed. CT was considered positive
      in case of: (a) gas in soft tissues, (b) multiple fluid collections, (c) absence
      or heterogeneity of tissue enhancement by the IV contrast, and (d) significant
      inflammatory changes under the fascia. NSTI was confirmed only by the presence of
      necrotic tissue during surgical exploration. NSTI was considered absent if
      surgical exploration failed to identify necrosis, or if the patient was
      successfully treated non-operatively. RESULTS: Of the 184 patients, 17 had a
      positive CT and hence underwent surgical exploration with NSTI being confirmed in
      13 of them (76%). Of the 167 patients that had a negative CT, 38 (23%) underwent
      surgical exploration due to the high clinical suspicion for NSTI and were all
      found to have non-necrotizing infections; the remaining 129 (77%) were managed
      non-operatively with successful resolution of symptoms. The sensitivity of CT in
      identifying NSTI was 100%, the specificity 98%, the positive predictive value
      76%, and the negative predictive value 100%. CONCLUSIONS: A negative IV contrast
      enhanced CT scan can reliably rule out the need for surgical intervention in
      patients with initial suspicion of NSTI.

PMID- 28762167
TI  - Elevated Myocardial Extracellular Volume Fraction in Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a genetic, X-linked recessive disease with
      an associated cardiomyopathy characterized by myocardial fibrosis leading to
      heart failure, arrhythmias, and death. Earlier detection and treatment of cardiac
      involvement in DMD hold potential to improve outcomes. Cardiovascular magnetic
      resonance (CMR) extracellular volume (ECV) quantification using T1 mapping is a
      histologically validated, non-invasive marker of diffuse fibrosis. This study
      aims to determine the ECV in a pediatric DMD population, and correlate it with
      metrics of left ventricular function. A retrospective review of pediatric DMD
      subjects who underwent CMR at a single institution. A total of 47 DMD patients
      (mean age 14 +/- 2 years) were included for analysis. Global myocardial ECV was
      significantly higher in the DMD group (29 +/- 6%) compared with published normal
      values (24 +/- 2%, p = 0.0001). Higher ECV values correlate with indices of left
      ventricular function, including decreased left ventricular ejection fraction (r =
      -0.46, p = 0.001) and indexed left ventricular end diastolic volume (r = 0.41, p
      = 0.004). ECV was not significantly higher in DMD patients with late gadolinium
      enhancement (LGE) (30 +/- 7%) compared to DMD patients without LGE (27 +/- 5%, p
      = 0.0717). CMR T1 mapping is a feasible method for quantification of ECV in
      patients with DMD. Global myocardial ECV is significantly higher in the DMD
      population compared to healthy controls and correlates with other metrics of
      myocardial function. Global myocardial ECV may serve as an important tool to
      determine cardiac involvement in DMD population and help guide medical
      management.

PMID- 28762169
TI  - Successful Surgical Treatment of Intractable Chylous Ascites Using the Lymphatic
      Cable Flap: A Retrospective Review Study.
AB  - OBJECTIVE: For evaluation of a novel surgical procedure for the treatment of
      chylous ascites. Chylous ascites is a debilitating condition associated with high
      morbidity and mortality rates. At least one-third of patients are refractory to
      medical therapy and may warrant further treatment. Traditional methods involving
      ligation of lymphatic fistulas or small bowel resection do not address the basic
      pathophysiologic mechanism of the underlying obstruction, and identification of
      chyloperitoneal fistulas may be challenging. METHODS: A novel flap based on deep
      inferior epigastric vessels with its surrounding lymphatic fatty tissue was
      designed in this study and transferred into abdominal cavity, with anastomosis to
      the fourth jejunal vessels. Three consecutive cases with chylous ascites treated
      by this vascularized lymphatic cable transfer were retrospectively reviewed.
      RESULTS: All three patients recovered from chylous ascites after the lymphatic
      cable transfer and tolerated regular diet well, with follow-up of 3 years at
      least. CONCLUSIONS: Lymphatic cable flap based on the deep inferior epigastric
      vessels could be a potential option for treatment of intractable chylous ascites,
      with safe and successful long-term outcomes in three consecutive patients. The
      proposed functional mechanism of the flap is bypass of the obstructed intra
      abdominal lymphatics to an extraperitoneal route as well as local
      lymphangiogenesis.

PMID- 28762170
TI  - Pheochromocytoma with Synchronous Ipsilateral Adrenal Cortical Adenoma.
AB  - BACKGROUND: Pheochromocytoma with synchronous ipsilateral adrenal cortical
      adenoma (PSCA) may present with mixed clinical, biochemical, and radiological
      features characteristic to each neoplasm subtype. METHODS: All patients with a
      pathological diagnosis of pheochromocytoma were evaluated for an ipsilateral
      cortical adenoma from 1994 through 2015. Retrospectively extracted data included
      indications for adrenalectomy, diagnostic workup (biochemical and radiographic),
      operative characteristics, pathological findings, and postoperative
      complications. RESULTS: Sixteen of 413 patients (4%) undergoing adrenalectomy for
      pheochromocytoma had a PSCA. Median patient age was 57.7 years (IQR 50.1, 63.1);
      50% were male. On imaging, 75% of the adrenal neoplasms were found incidentally
      and only 50% were reported to have a synchronous ipsilateral neoplasm based on
      imaging findings. Clinically important cortical hormone secretion was diagnosed
      in 38% of these patients; 25% had glucocorticoid secretory autonomy; and 13% had
      primary aldosteronism. CONCLUSION: Physicians should be aware that adrenal
      neoplasms with mixed diagnostic findings may represent PSCA. Evaluation should be
      performed on this co-occurrence to prevent perioperative complications from
      resection of an unexpected secretory cortical neoplasm.

PMID- 28762171
TI  - Addition of an antiangiogenic therapy, bevacizumab, to gemcitabine plus
      oxaliplatin improves survival in advanced biliary tract cancers.
AB  - Background The prognosis of patients with metastatic carcinoma of the biliary
      tract (mBTC) is poor and a systemic therapy with gemcitabine and platinum-based
      is the gold standard. The addition of bevacizumab to the chemotherapy might
      increase patients' survival. Our aim was to assess and compare the efficacy of
      GEMOX (gemcitabine and oxaliplatin regimen) plus bevacizumab to GEMOX alone in
      mBTC. Methods Patients with mBTC who received the GEMOX-bevacizumab (n = 32;
      Group A) or GEMOX (n = 25; Group B) regimen as first-line treatment were
      compared. Treatment was repeated every two weeks until disease progression or
      unacceptable adverse effects occurred. The primary evaluation criterion was the
      progression-free survival (PFS). Results A quarter of patients (8/32) from Group
      A and a fifth of patients (13/25) from Group B had an objective response. The
      median PFS was 6.48 months and 3.72 months in Group A and B, respectively (p =
      0.049). The median OS was 11.31 months and 10.34 months in Group A and B,
      respectively. Grade 3/4 sepsis was identified in 9.4% and 12% in Group A and B,
      respectively, (p = 0.64). Conclusion In mBTC, the addition of bevacizumab to
      GEMOX increased the progression-free survival and was associated with manageable
      toxicity. These data pave the way for further evaluation of antiangiogenic agents
      in mBTC.

PMID- 28762172
TI  - Mechanical Circulatory Support for Decompensated Heart Failure.
AB  - PURPOSE OF REVIEW: Cardiogenic shock from decompensated heart failure is
      associated with significant morbidity and mortality. Mechanical circulatory
      support (MCS) improves haemodynamics and reverses organ dysfunction in critically
      ill patients with cardiogenic shock. This paper summarises the main modalities of
      mechanical support and their physiological impact, practical considerations,
      advantages and disadvantages to facilitate a holistic approach in managing a
      potentially lethal pathology. RECENT FINDINGS: To date, there remains a lack of
      large randomised controlled trials to support the use of any mechanical support
      strategy. Consequently, meta-analyses, registry data and expert consensus in the
      form of society guidelines are relied upon. Currently, randomised trials are in
      progress to assess the efficacy of a percutaneous assist device (Impella) and
      extracorporeal membrane oxygenation. Mechanical support options are centred
      around the use of counter pulsation and percutaneous assist devices and the use
      of an extracorporeal pump and are hence varied in means of application, degree of
      haemodynamic benefit and potential complications. Regardless of future
      innovations, a timely multidisciplinary approach that incorporates both patient
      and institutional considerations will always be crucial to a successful outcome.

PMID- 28762174
TI  - Ethnic Chinese medicine, borderless civilization - On the identity of humane and
      scientific nature of Chinese and Western medicines.

PMID- 28762173
TI  - Methylene blue and its analogues as antidepressant compounds.
AB  - Methylene Blue (MB) is considered to have diverse medical applications and is a
      well-described treatment for methemoglobinemias and ifosfamide-induced
      encephalopathy. In recent years the focus has shifted to MB as an antimalarial
      agent and as a potential treatment for neurodegenerative disorders such as
      Alzheimer's disease. Of interest are reports that MB possesses antidepressant and
      anxiolytic activity in pre-clinical models and has shown promise in clinical
      trials for schizophrenia and bipolar disorder. MB is a noteworthy inhibitor of
      monoamine oxidase A (MAO-A), which is a well-established target for
      antidepressant action. MB is also recognized as a non-selective inhibitor of
      nitric oxide synthase (NOS) and guanylate cyclase. Dysfunction of the nitric
      oxide (NO)-cyclic guanosine monophosphate (cGMP) cascade is strongly linked to
      the neurobiology of mood, anxiety and psychosis, while the inhibition of NOS
      and/or guanylate cyclase has been associated with an antidepressant response.
      This action of MB may contribute significantly to its psychotropic activity.
      However, these disorders are also characterised by mitochondrial dysfunction and
      redox imbalance. By acting as an alternative electron acceptor/donor MB restores
      mitochondrial function, improves neuronal energy production and inhibits the
      formation of superoxide, effects that also may contribute to its therapeutic
      activity. Using MB in depression co-morbid with neurodegenerative disorders, like
      Alzheimer's and Parkinson's disease, also represents a particularly relevant
      strategy. By considering their physicochemical and pharmacokinetic properties,
      analogues of MB may provide therapeutic potential as novel multi-target
      strategies in the treatment of depression. In addition, low MAO-A active
      analogues may provide equal or improved response with a lower risk of adverse
      effects.

PMID- 28762176
TI  - A salty landscape of fear: responses of fish and zooplankton to freshwater
      salinization and predatory stress.
AB  - Predator-prey relationships are altered by anthropogenic contaminants. Road salt
      is a widespread contaminant among freshwater ecosystems, yet a relatively
      understudied subject in community ecology. Unknown is whether road salt
      salinization interacts with predatory stress to influence the growth, behavior,
      or reproduction of freshwater organisms. Using rainbow trout (Oncorhynchus
      mykiss) and zooplankton (Daphnia pulex), we exposed them to variable levels of
      road salt (NaCl) crossed with the presence or absence of alarm cues or
      kairomones. Alarm cue reduced trout activity and aggression and increased
      shoaling behavior. Road salt reduced trout growth in the high compared to
      moderate salt concentration, but neither concentration was different from the
      control. There was no interaction between alarm cues and salt for trout. Road
      salt and predatory stress had an additive effect on Daphnia abundance. Predatory
      stress decreased Daphnia abundance by 11%. Compared to the control, salt
      decreased Daphnia abundance by 40% in 860 mg Cl-/L and 79% in 1300 mg Cl-/L, and
      by the final day abundance was reduced by 85% in 1300 mg Cl-/L. Road salt and
      predatory stress had an interactive effect on Daphnia reproduction. Predatory
      stress in control water and moderate salt levels (230 mg Cl-/L) increased sexual
      reproduction of Daphnia, but these responses disappeared at high salt
      concentrations. Thus, road salt could limit reproductive adaptations to natural
      and anthropogenic stressors in Daphnia. Our results indicate road salt
      salinization could alter zooplankton population dynamics directly and by
      interacting with predatory stress, which might affect energy flow through
      freshwater food webs.

PMID- 28762177
TI  - Iatrogenic recto-vaginal fistula as a late consequence of failed primary repair
      of genital injury caused by sexual assault.

PMID- 28762178
TI  - The influence of duloxetine on detrusor overactivity in rats with depression
      induced by 13-cis-retinoic acid.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the efficacy of
      duloxetine in an animal model of detrusor overactivity induced by depression.
      METHODS: After 6 weeks of 13-cis-retinoic acid administration at a dose of 1
      mg/kg/day, rats were given duloxetine at a dose of 1 mg/kg. This was followed by
      conscious cystometry, a forced swim test, and locomotor activity measurement. The
      levels of corticotropin-releasing factor (CRF) in the hypothalamus, amygdala and
      plasma were also determined. RESULTS: Duloxetine treatment led to a reduction in
      detrusor overactivity symptoms induced by the retinoid. Decreases were observed
      in cystometric parameters including the detrusor overactivity index, and the
      amplitude and frequency of nonvoiding contractions, while increases were seen in
      bladder compliance and the volume threshold to elicit nonvoiding contractions. No
      statistically significant differences were found in basal pressure, threshold
      pressure, micturition voiding pressure, postvoid residual , volume threshold,
      voiding efficiency, intercontraction interval, bladder contraction duration or
      relaxation time. Duloxetine also reduced the immobility time to that observed in
      control animals, while it did not affect locomotor activity. Its effects also
      included lowering of the CRF levels in the hypothalamus, amygdala and plasma,
      which increased following the prior administration of the retinoid. The plasma
      level of 13-cis-retinoic acid in rats corresponded to the levels found in humans.
      CONCLUSIONS: This is the first study showing the efficacy of duloxetine in an
      animal model of detrusor overactivity induced by depression. Further studies in
      patients with detrusor overactivity and coexisting depression are warranted to
      confirm these experimental results.

PMID- 28762179
TI  - Vaginal laxity: what does this symptom mean?
AB  - INTRODUCTION AND HYPOTHESIS: Vaginal laxity is a poorly understood symptom of
      pelvic floor dysfunction. The purpose of this study was to investigate
      associations between the symptom of vaginal laxity and its bother on the one
      hand, and demographic data, other symptoms, and findings on examination on the
      other hand. METHODS: This was a retrospective observational study at a tertiary
      urogynecological unit. A total of 337 patients were seen for a standardized
      interview, clinical examination (ICS POP-Q) and 4D translabial ultrasonography.
      Stored imaging data were analyzed offline to evaluate functional pelvic floor
      anatomy and investigate associations with symptoms and other findings. RESULTS:
      Of the 337 women seen during the study period, 13 were excluded due to missing
      data, leaving 324. Vaginal laxity was reported by 24% with a mean bother of 5.7.
      In a univariate analysis, this symptom was associated with younger age, vaginal
      parity, POP symptoms and bother, clinically and sonographically determined POP
      and hiatal area on Valsalva maneuver. CONCLUSIONS: Vaginal laxity or 'looseness'
      is common in our urogynecology service at a prevalence of 24%. The associated
      bother is almost as high as the bother associated with conventional prolapse
      symptoms. It is associated with younger age, vaginal parity, symptoms of
      prolapse, prolapse bother and objective prolapse on POP-Q examination and
      imaging, suggesting that vaginal laxity may be considered a symptom of prolapse.
      The strongest associations were found with gh + pb and hiatal area on Valsalva
      maneuver, suggesting that vaginal laxity is a manifestation of levator ani
      hyperdistensibility.

PMID- 28762175
TI  - Genetic mutations in RNA-binding proteins and their roles in ALS.
AB  - Mutations in genes that encode RNA-binding proteins (RBPs) have emerged as
      critical determinants of neurological diseases, especially motor neuron disorders
      such as amyotrophic lateral sclerosis (ALS). RBPs are involved in all aspects of
      RNA processing, controlling the life cycle of RNAs from synthesis to degradation.
      Hallmark features of RBPs in neuron dysfunction include misregulation of RNA
      processing, mislocalization of RBPs to the cytoplasm, and abnormal aggregation of
      RBPs. Much progress has been made in understanding how ALS-associated mutations
      in RBPs drive pathogenesis. Here, we focus on several key RBPs involved in ALS
      TDP-43, HNRNP A2/B1, HNRNP A1, FUS, EWSR1, and TAF15-and review our current
      understanding of how mutations in these proteins cause disease.

PMID- 28762181
TI  - Sternum-splitting anterior approach following posterior decompression and fusion
      in patients with massive ossification of the posterior longitudinal ligament in
      the upper thoracic spine: report of 2 cases and literature review.
AB  - PURPOSE: Anterior approach to the upper thoracic spine is difficult. It is
      important for spine surgeons to know the indication and the effect of anterior
      decompression for upper thoracic lesions and also to recognize the complications
      which are related to the approach with sternotomy. We present two patients for
      whom we took the sternum-splitting anterior approach for thoracic ossification of
      the posterior longitudinal ligament (OPLL) following posterior decompression and
      fusion surgery; the clinical course and surgical outcome are discussed, with
      particular reference to complication avoidance and also we review the previous
      literature. METHODS: We present two cases with severe upper thoracic OPLL. The
      maximum occupying ratio of OPLL against the spinal canal was more than 80% in
      both cases. Posterior decompression and fusion were not effective and, therefore,
      anterior surgery with sternotomy was carried out. RESULTS: Cerebrospinal fluid
      leak was encountered with the removal of OPLL using the anterior approach.
      Subsequently, a polyglycolic acid sheet was used to cover the defect in the dura
      matter; a thoracic drainage system with a continuous suction unit was positioned
      at the surgical wound to avoid fluid retention in the mediastinum. In addition,
      we facilitated spinal drainage from the lumbar level. These procedures resulted
      in no complication caused by fluid retention in the mediastinum. CONCLUSION: Both
      a safe surgical approach and preventive measures to alleviate postoperative
      complications are mandatory in difficult cases with thoracic OPLL.

PMID- 28762180
TI  - Optimum support by high-flow nasal cannula in acute hypoxemic respiratory
      failure: effects of increasing flow rates.
AB  - PURPOSE: Limited data exist on the correlation between higher flow rates of high
      flow nasal cannula (HFNC) and its physiologic effects in patients with acute
      hypoxemic respiratory failure (AHRF). We assessed the effects of HFNC delivered
      at increasing flow rate on inspiratory effort, work of breathing, minute
      ventilation, lung volumes, dynamic compliance and oxygenation in AHRF patients.
      METHODS: A prospective randomized cross-over study was performed in non-intubated
      patients with patients AHRF and a PaO2/FiO2 (arterial partial pressure of
      oxygen/fraction of inspired oxygen) ratio of <=300 mmHg. A standard non-occlusive
      facial mask and HFNC at different flow rates (30, 45 and 60 l/min) were randomly
      applied, while maintaining constant FiO2 (20 min/step). At the end of each phase,
      we measured arterial blood gases, inspiratory effort, based on swings in
      esophageal pressure (DeltaPes) and on the esophageal pressure-time product
      (PTPPes), and lung volume, by electrical impedance tomography. RESULTS: Seventeen
      patients with AHRF were enrolled in the study. At increasing flow rate, HFNC
      reduced DeltaPes (p < 0.001) and PTPPes (p < 0.001), while end-expiratory lung
      volume (DeltaEELV), tidal volume to DeltaPes ratio (V T/DeltaPes, which
      corresponds to dynamic lung compliance) and oxygenation improved (p < 0.01 for
      all factors). Higher HFNC flow rate also progressively reduced minute ventilation
      (p < 0.05) without any change in arterial CO2 tension (p = 0.909). The decrease
      in DeltaPes, PTPPes and minute ventilation at increasing flow rates was better
      described by exponential fitting, while DeltaEELV, V T/DeltaPes and oxygenation
      improved linearly. CONCLUSIONS: In this cohort of patients with AHRF, an
      increasing HFNC flow rate progressively decreased inspiratory effort and improved
      lung aeration, dynamic compliance and oxygenation. Most of the effect on
      inspiratory workload and CO2 clearance was already obtained at the lowest flow
      rate.

PMID- 28762182
TI  - Diet-induced hypercholesterolemia alters liver glycosaminoglycans and associated
      lipoprotein receptors in rats.
AB  - Glycosaminoglycans (GAGs) play an important role in lipoprotein metabolism. In
      liver, it facilitates the uptake of remnants through receptor-independent
      endocytosis. However, changes in liver GAGs during diet-induced
      hypercholesterolemia with normal levels of fat feeding are unknown. Present paper
      highlights the effect of diet-induced hypercholesterolemia with normal levels
      (5%) of fat on liver GAGs and other associated lipoprotein receptors.
      Hypercholesterolemia was induced in rats by feeding diet supplemented with 0.5%
      cholesterol and 0.125% bile salts. Hypercholesterolemia showed significantly
      decreased GAGs of both heparan sulfate (HS) and chondroitin sulfate/dermatan
      sulfate (CS/DS) classes of molecules. Quantitative real-time polymerase chain
      reaction analysis of GAG biosynthetic enzymes and other genes revealed
      significant changes in expression profile. The decrease in GAGs was prevented by
      simvastatin treatment; a drug that inhibits endogenous cholesterol synthesis that
      was used as a positive control in our study. Furthermore, there was a
      comparatively decreased binding of GAGs from hypercholesterolemic rats to
      lipoprotein lipase. LRP1 which plays a major role in lipoprotein uptake was also
      significantly decreased, and it was attenuated in simvastatin-treated
      hypercholesterolemic rats. Furthermore, LDLR and ApoE were also decreased
      significantly in liver of hypercholesterolemic rats. Thus, diet-induced
      hypercholesterolemia results in dysregulation of cholesterol homeostasis
      apparently through changes in GAGs in conjunction with other associated players.

PMID- 28762183
TI  - Novel nanoformulation to mitigate co-effects of drugs of abuse and HIV-1
      infection: towards the treatment of NeuroAIDS.
AB  - Drug abuse (e.g., methamphetamine-Meth or cocaine-Coc) is one of the major risk
      factors for becoming infected with HIV-1, and studies show that in combination,
      drug abuse and HIV-1 lead to significantly greater damage to CNS. To overcome
      these issues, we have developed a novel nanoformulation (NF) for drug-abusing
      population infected with HIV-1. In this work, a novel approach was developed for
      the co-encapsulation of Nelfinavir (Nel) and Rimcazole (Rico) using layer-by
      layer (LbL) assembled magnetic nanoformulation for the cure of neuroAIDS.
      Developed NF was evaluated for blood-brain barrier (BBB) transmigration, cell
      uptake, cytotoxicity and efficacy (p24 assay) in HIV-1 infected primary astrocyte
      (HA) in presence or absence of Coc and Meth. Developed magnetic nanoformulation
      (NF) fabricated using the LbL approach exhibited higher amounts of drug loading
      (Nel and Rico) with 100% release of both the therapeutic agents in a sustained
      manner for 8 days. NF efficacy studies indicated a dose-dependent decrease in p24
      levels in HIV-1-infected HA (~55%) compared to Coc + Meth treated (~50%). The
      results showed that Rico significantly subdued the effect of drugs of abuse on
      HIV infectivity. NF successfully transmigrated (38.8 +/- 6.5%) across in vitro
      BBB model on the application of an external magnetic field and showed >90% of
      cell viability with efficient cell uptake. In conclusion, our proof of concept
      study revealed that sustained and concurrent release of sigma sigma1 antagonist
      and anti-HIV drug from the developed novel sustained release NF can overcome the
      exacerbated effects of drugs of abuse in HIV infection and may solve the issue of
      medication adherence in the drug-abusing HIV-1 infected population.

PMID- 28762184
TI  - Nef is secreted in exosomes from Nef.GFP-expressing and HIV-1-infected human
      astrocytes.
AB  - HIV-1 infection of the central nervous system causes HIV-associated
      neurocognitive disorders, even in aviremic patients. Although astrocyte
      malfunction was associated to these disorders, their implication is overshadowed
      by contributions of microglia and macrophages. Astrocytes are infected with HIV-1
      in vivo and express a relevant amount of viral protein Nef. Nef was shown to
      stimulate its own release in exosomes from diverse cell types, which in turn have
      damaging effects on neighboring cells. Using immunoblotting and electron
      microscopy, we showed that human astrocytes expressing Nef.GFP similarly release
      Nef in exosomes. Importantly, Nef.GFP expression increases the secretion of
      exosomes from human astrocytes up to 5.5-fold, as determined by total protein
      content and nanoparticle tracking analysis. Protein analysis of exosomes and
      viruses separated on iodixanol gradient further showed that native or pseudotyped
      HIV-1-infected human astrocytes release exosomes, which contain Nef. Our results
      provide the basis for future studies of the damaging role of Nef-exosomes
      produced by HIV-infected astrocytes on the central nervous system.

PMID- 28762185
TI  - Consideration of the Intracranial Pressure Threshold Value for the Initiation of
      Traumatic Brain Injury Treatment: A Xenon CT and Perfusion CT Study.
AB  - BACKGROUND: Monitoring of intracranial pressure (ICP) is considered to be
      fundamental for the care of patients with severe traumatic brain injury (TBI) and
      is routinely used to direct medical and surgical therapy. Accordingly, some
      guidelines for the management of severe TBI recommend that treatment be initiated
      for ICP values >20 mmHg. However, it remained to be accounted whether there is a
      scientific basis to this instruction. The purpose of the present study was to
      clarify whether the basis of ICP values >20 mmHg is appropriate. SUBJECT AND
      METHODS: We retrospectively reviewed 25 patients with severe TBI who underwent
      neuroimaging during ICP monitoring within the first 7 days. We measured cerebral
      blood flow (CBF), mean transit time (MTT), cerebral blood volume (CBV), and ICP
      71 times within the first 7 days. RESULTS: Although the CBF, MTT, and CBV values
      were not correlated with the ICP value at ICP values <=20 mmHg, the CBF value was
      significantly negatively correlated with the ICP value (r = -0.381, P < 0.05) at
      ICP values >20 mmHg. The MTT value was also significantly positively correlated
      with the ICP value (r = 0.638, P < 0.05) at ICP values >20 mmHg. CONCLUSION: The
      cerebral circulation disturbance increased with the ICP value. We demonstrated
      the cerebral circulation disturbance at ICP values >20 mmHg. This study suggests
      that an ICP >20 mmHg is the threshold to initiate treatments. An active treatment
      intervention would be required for severe TBI when the ICP was >20 mmHg.

PMID- 28762186
TI  - Laparoscopic Liver Resection Using the Lateral Approach from Intercostal Ports in
      Segments VI, VII, and VIII.
AB  - BACKGROUND: Laparoscopic liver resection (LLR) has been developed as a minimally
      invasive surgery. However, challenges such as difficulty securing visibility and
      limited control of forceps make it difficult to complete LLR in hepatic segments
      VI, VII, and VIII. To overcome these challenges, we devised a surgical technique
      using intercostal ports. We termed this approach the lateral approach. This work
      describes our experience performing LLR using this approach and discusses the
      safety and effectiveness of this approach. METHODS: Between April 2011 and
      December 2016, data from 91 patients who underwent LLR with or without the
      intercostal port at a single institution were retrospectively analyzed regarding
      surgical outcomes, safety, and utility. RESULTS: LLR was performed for 32
      patients with the intercostal port and for 59 patients without the intercostal
      port. The conversion rates to open surgery with and without intercostal ports
      were 3.1 and 25.4% (P = 0.008). In hepatic segments VII and VIII, the rates of
      conversion to open surgery were significantly lower for cases involving
      intercostal ports (6.7 vs. 42.9 and 0 vs. 38.9%; P = 0.035 and 0026,
      respectively); however, there were no differences in hepatic segment VI (0 vs.
      7.4%; P = 0.563). There were no differences in operative time, blood loss volume,
      surgical margin, curative resection rate, or postoperative complication rate for
      LLR in all segments (VI, VII, and VIII). No adverse events due to placement of
      the intercostal port were observed in this set of patients. CONCLUSION: LLR using
      the lateral approach and intercostal ports for hepatic segments VII and VIII
      resulted in a significant decrease in conversion rates to open surgery.

PMID- 28762187
TI  - The choroid plexus is a key cerebral invasion route for T cells after stroke.
AB  - Neuroinflammation contributes substantially to stroke pathophysiology. Cerebral
      invasion of peripheral leukocytes-particularly T cells-has been shown to be a key
      event promoting inflammatory tissue damage after stroke. While previous research
      has focused on the vascular invasion of T cells into the ischemic brain, the
      choroid plexus (ChP) as an alternative cerebral T-cell invasion route after
      stroke has not been investigated. We here report specific accumulation of T cells
      in the peri-infarct cortex and detection of T cells as the predominant population
      in the ipsilateral ChP in mice as well as in human post-stroke autopsy samples. T
      cell migration from the ChP to the peri-infarct cortex was confirmed by in vivo
      cell tracking of photoactivated T cells. In turn, significantly less T cells
      invaded the ischemic brain after photothrombotic lesion of the ipsilateral ChP
      and in a stroke model encompassing ChP ischemia. We detected a gradient of CCR2
      ligands as the potential driving force and characterized the neuroanatomical
      pathway for the intracerebral migration. In summary, our study demonstrates that
      the ChP is a key invasion route for post-stroke cerebral T-cell invasion and
      describes a CCR2-ligand gradient between cortex and ChP as the potential driving
      mechanism for this invasion route.

PMID- 28762188
TI  - A comparative study of U937 cell size changes during apoptosis initiation by flow
      cytometry, light scattering, water assay and electronic sizing.
AB  - A decrease in flow cytometric forward light scatter (FSC) is commonly interpreted
      as a sign of apoptotic cell volume decrease (AVD). However, the intensity of
      light scattering depends not only on the cell size but also on its other
      characteristics, such as hydration, which may affect the scattering in the
      opposite way. That makes estimation of AVD by FSC problematic. Here, we aimed to
      clarify the relationship between light scattering, cell hydration (assayed by
      buoyant density) and cell size by the Coulter technique. We used human lymphoid
      cells U937 exposed to staurosporine, etoposide or hypertonic stress as an
      apoptotic model. An initial increase in FSC was found to occur in apoptotic cells
      treated with staurosporine and hypertonic solutions; it is accompanied by cell
      dehydration and is absent in apoptosis caused by etoposide that is consistent
      with the lack of dehydration in this case. Thus, the effect of dehydration on the
      scattering signal outweighs the effect of reduction in cell size. The subsequent
      FSC decrease, which occurred in parallel to accumulation of annexin-positive
      cells, was similar in apoptosis caused by all three types of inducers. We
      conclude that an increase, but not a decrease in light scattering, indicates the
      initial cell volume decrease associated with apoptotic cell dehydration.

PMID- 28762189
TI  - Prediction of lateral pelvic lymph node metastasis from lower rectal cancer using
      magnetic resonance imaging and risk factors for metastasis: Multicenter study of
      the Lymph Node Committee of the Japanese Society for Cancer of the Colon and
      Rectum.
AB  - PURPOSE: The goal of the study was to examine prediction of lateral pelvic lymph
      node (LPLN) metastasis from lower rectal cancer using a logistic model including
      risk factors for LPLN metastasis and magnetic resonance imaging (MRI) clinical
      LPLN (cLPLN) status, compared to prediction based on MRI alone. METHODS: The
      subjects were 272 patients with lower rectal cancer who underwent MRI prior to
      mesorectal excision combined with LPLN dissection (LPLD) at six institutes. No
      patients received neoadjuvant therapy. Prediction models for right and left
      pathological LPLN (pLPLN) metastasis were developed using cLPLN status,
      histopathological grade, and perirectal lymph node (PRLN) status. For evaluation,
      data for patients with left LPLD were substituted into the right-side equation
      and vice versa. RESULTS: Left LPLN metastasis was predicted using the right-side
      model with accuracy of 86.5%, sensitivity 56.4%, specificity 92.7%, positive
      predictive value (PPV) 61.1%, and negative predictive value (NPV) 91.2%, while
      these data using MRI cLPLN status alone were 80.4, 76.9, 81.2, 45.5, and 94.5%,
      respectively. Similarly, right LPLN metastasis was predicted using the left-side
      equation with accuracy of 83.8%, sensitivity 57.8%, specificity 90.4%, PPV 60.5%,
      and NPV 89.4%, and the equivalent data using MRI alone were 78.4, 68.9, 80.8,
      47.7, and 91.1%, respectively. The AUCs for the right- and left-side equations
      were significantly higher than the equivalent AUCs for MRI cLPLN status alone.
      CONCLUSIONS: A logistic model including risk factors for LPLN metastasis and MRI
      findings had significantly better performance for prediction of LPLN metastasis
      compared with a model based on MRI findings alone.

PMID- 28762190
TI  - Preoperative chemoradiotherapy changes the size criterion for predicting lateral
      lymph node metastasis in lower rectal cancer.
AB  - PURPOSE: The purpose of this study was to identify the size criteria of lateral
      lymph node metastasis in lower rectal cancer both in patients who underwent
      preoperative CRT and those who did not. METHODS: This study enrolled 150 patients
      who underwent resection for primary lower rectal adenocarcinoma with lateral
      lymph node dissection between 2013 and 2015. Patients were divided into two
      groups: the CRT group, treated with preoperative chemoradiotherapy before
      surgery, and the non-CRT group, treated with surgery alone. The short-axis
      diameter of each dissected lateral lymph node was measured. Receiver-operating
      characteristic curves were generated to reveal the optimal cutoff values for
      determining lateral lymph node metastasis in both groups. RESULTS: In the non-CRT
      group (n = 131), the ROC curve demonstrated that the optimal cutoff value for
      determining metastasis was 6.0 mm, with a sensitivity of 78.5% and specificity of
      82.9%, and the AUC was 0.845. In comparison, in the CRT group (n = 19), the
      optimal cutoff value was 5.0 mm, with a sensitivity of 71.4% and specificity of
      85.3% and an AUC of 0.836. CONCLUSION: The cutoff size for determining lateral
      lymph node metastasis was smaller in the CRT group than in the non-CRT group.

PMID- 28762191
TI  - Inhibition of Autophagy is Involved in the Protective Effects of Ginsenoside Rb1
      on Spinal Cord Injury.
AB  - Spinal cord injury (SCI) is a devastating neurological disorder. Autophagy is
      induced and plays a crucial role in SCI. Ginsenoside Rb1 (Rb1), one of the major
      active components extracted from Panax Ginseng CA Meyer, has exhibited
      neuroprotective effects in various neurodegenerative diseases. However, it
      remains unknown whether autophagy is involved in the neuroprotection of Rb1 on
      SCI. In this study, we examined the regulation of autophagy following Rb1
      treatment and its involvement in the Rb1-induced neuroprotection in SCI and in
      vitro injury model. Firstly, we found that Rb1 treatment decreased the loss of
      motor neurons and promoted function recovery in the SCI model. Furthermore, we
      found that Rb1 treatment inhibited autophagy in neurons, and suppressed neuronal
      apoptosis and autophagic cell death in the SCI model. Finally, in the in vitro
      injury model, Rb1 treatment increased the viability of PC12 cells and suppressed
      apoptosis by inhibiting excessive autophagy, whereas stimulation of autophagy by
      rapamycin abolished the anti-apoptosis effect of Rb1. Taken together, these
      findings suggest that the inhibition of autophagy is involved in the
      neuroprotective effects of Rb1 on SCI.

PMID- 28762192
TI  - A Comprehensive Review on Copemyl(r).
AB  - Economic sustainability is of paramount importance in the rapidly evolving
      therapeutic scenario of multiple sclerosis (MS). Glatiramoids are a class of
      drugs whose forefather, glatiramer acetate, has been used as a disease modifying
      drug (DMD) in patients with MS for over 20 years. Its patent expired in 2015; new
      versions of such drug are nowadays available on the market, potentially
      contributing to lowering prices and enhancing a better allocation of economic
      resources. In this review, we analyze the recommendations underlying the approval
      of both generic drugs and biosimilars by regulatory authorities, and we provide
      methodological tools to contextualize the design of studies on these new classes
      of drugs. We examine in more detail the preclinical and clinical data of
      Copemyl(r), a new member of the glatiramoid class, focusing on its biological and
      immunological properties and illustrating randomized controlled trials that led
      to its authorization.

PMID- 28762193
TI  - Probiotic Features of Lactic Acid Bacteria Isolated from a Diverse Pool of
      Traditional Greek Dairy Products Regarding Specific Strain-Host Interactions.
AB  - The increased consumers' interest on the positive role of food in wellbeing and
      health underscores the need to determine new probiotic microorganisms. Triggered
      by the fact that artisanal food products can be a valuable source of novel
      probiotic strains, 106 lactic acid bacteria, all isolated from traditional Greek
      dairy products, namely Feta, Kasseri, Xynotyri, Graviera, Formaela, Galotyri, and
      Kefalotyri cheeses as well as yogurt and milk, were studied for probiotic
      properties. Based on their survival at pH 2.5 and their stability in the presence
      of bile salts, 20 strains were selected for further analysis. These strains
      exhibited diverse susceptibility to commonly used antibiotics, while none was
      hemolytic. Seven out of the 20 strains produced functional bile salt hydrolases
      in vitro. The only antimicrobial activity detected of Streptococcus thermophilus
      ACA-DC 26 against the oral pathogen Streptococcus mutans LMG 14558T was
      attributed to compound(s) of proteinaceous nature. Two Lactobacillus plantarum
      strains, namely ACA-DC 2640 and ACA-DC 4039, displayed the highest adhesion
      according to a collagen-based microplate assay and by using EtaTau-29 and Caco-2
      cells. Co-cultivation of THP-1 cells with selected strains indicated a tendency
      for anti-inflammatory modulation by Lactobacillus plantarum ACA-DC 2640 as well
      as Streptococcus thermophilus ACA-DC 26 and ACA-DC 170, as shown by an increase
      in IL10 mRNA levels. Moreover, milk cell-free supernatants of Lactobacillus
      plantarum ACA-DC 2640 and ACA-DC 4039 exhibited strong angiotensin I-converting
      enzyme inhibition. To conclude, new isolates presenting interesting probiotic
      features were described and should be further investigated as health-promoting
      factors.

PMID- 28762194
TI  - Selective removal of carious lesion with Er:YAG laser followed by dentin
      biomodification with chitosan.
AB  - The aim of this study was to evaluate the effect of Er:YAG laser for selective
      removal of carious lesion, followed by biomodification with chitosan gel where
      the subsurface microhardness, chemical composition, and morphological changes of
      the residual caries-affected dentin were examined. Artificial dentinal lesions
      were created by pH-cycling method (14 days) in 104 bovine specimens (5 * 5 mm).
      Specimens were randomly divided according to the carious removal method: bur (low
      speed handpiece) or Er:YAG laser (250 mJ/4 Hz). Specimens were treated with 35%
      phosphoric acid and were subdivided into two groups according to dentin
      biomodification: without chitosan (control) and 2.5% chitosan. Forty specimens
      were restored with an adhesive system and composite resin. Subsurface
      microhardness tests were performed in sound dentin, caries-affected dentin,
      residual caries-affected dentin, and after the restoration. The other 64
      specimens were subjected to SEM-EDS atomic analysis. Data were statistically
      analyzed (p < 0.05). After the Er:YAG laser excavation, the microhardness value
      of residual caries-affected dentin was higher (p < 0.05) than bur-treated dentin.
      A significant decrease in the amount of Ca, P, and Ca/P ratio was found after the
      removal of carious lesions with Er:YAG laser (p < 0.05). The biomodification with
      chitosan did not influence the microhardness and atomic percentage of Ca, P, and
      Ca/P ratio of residual caries-affected dentin (p > 0.05). SEM analysis showed
      morphological changes on residual caries-affected dentin (p > 0.05). The
      selective removal of carious dentin with Er:YAG laser increased microhardness of
      residual caries-affected dentin, changing its surface morphology and chemical
      composition. The biomodification with chitosan did not influence the structural
      and chemical composition of residual caries-affected dentin.

PMID- 28762195
TI  - No evidence for self-recognition in a small passerine, the great tit (Parus
      major) judged from the mark/mirror test.
AB  - Self-recognition is a trait presumed to be associated with high levels of
      cognition and something previously considered to be exclusive to humans and
      possibly apes. The most common test of self-recognition is the mark/mirror test
      of whether an animal can understand that it sees its own reflection in a mirror.
      The usual design is that an animal is marked with a colour spot somewhere on the
      body where the spot can only be seen by the animal by using a mirror. Very few
      species have passed this test, and among birds, only magpies have been
      affirmatively demonstrated to pass it. In this study, we tested great tits (Parus
      major), small passerines, that are known for their innovative foraging skills and
      good problem-solving abilities, in the mirror self-recognition test. We found no
      indication that they have any ability of this kind and believe that they are
      unlikely to be capable of this type of self-recognition.

PMID- 28762196
TI  - Ultrasound image-based thyroid nodule automatic segmentation using convolutional
      neural networks.
AB  - PURPOSE: Delineation of thyroid nodule boundaries from ultrasound images plays an
      important role in calculation of clinical indices and diagnosis of thyroid
      diseases. However, it is challenging for accurate and automatic segmentation of
      thyroid nodules because of their heterogeneous appearance and components similar
      to the background. In this study, we employ a deep convolutional neural network
      (CNN) to automatically segment thyroid nodules from ultrasound images. METHODS:
      Our CNN-based method formulates a thyroid nodule segmentation problem as a patch
      classification task, where the relationship among patches is ignored.
      Specifically, the CNN used image patches from images of normal thyroids and
      thyroid nodules as inputs and then generated the segmentation probability maps as
      outputs. A multi-view strategy is used to improve the performance of the CNN
      based model. Additionally, we compared the performance of our approach with that
      of the commonly used segmentation methods on the same dataset. RESULTS: The
      experimental results suggest that our proposed method outperforms prior methods
      on thyroid nodule segmentation. Moreover, the results show that the CNN-based
      model is able to delineate multiple nodules in thyroid ultrasound images
      accurately and effectively. In detail, our CNN-based model can achieve an average
      of the overlap metric, dice ratio, true positive rate, false positive rate, and
      modified Hausdorff distance as [Formula: see text], [Formula: see text],
      [Formula: see text], [Formula: see text], [Formula: see text] on overall folds,
      respectively. CONCLUSION: Our proposed method is fully automatic without any user
      interaction. Quantitative results also indicate that our method is so efficient
      and accurate that it can be good enough to replace the time-consuming and tedious
      manual segmentation approach, demonstrating the potential clinical applications.

PMID- 28762198
TI  - Directly watching biomolecules in action by high-speed atomic force microscopy.
AB  - Proteins are dynamic in nature and work at the single molecule level. Therefore,
      directly watching protein molecules in dynamic action at high spatiotemporal
      resolution must be the most straightforward approach to understanding how they
      function. To make this observation possible, high-speed atomic force microscopy
      (HS-AFM) has been developed. Its current performance allows us to film biological
      molecules at 10-16 frames/s, without disturbing their function. In fact, dynamic
      structures and processes of various proteins have been successfully visualized,
      including bacteriorhodopsin responding to light, myosin V walking on actin
      filaments, and even intrinsically disordered proteins undergoing order/disorder
      transitions. The molecular movies have provided insights that could not have been
      reached in other ways. Moreover, the cantilever tip can be used to manipulate
      molecules during successive imaging. This capability allows us to observe changes
      in molecules resulting from dissection or perturbation. This mode of imaging has
      been successfully applied to myosin V, peroxiredoxin and doublet microtubules,
      leading to new discoveries. Since HS-AFM can be combined with other techniques,
      such as super-resolution optical microscopy and optical tweezers, the usefulness
      of HS-AFM will be further expanded in the near future.

PMID- 28762197
TI  - Sequence, Structural Analysis and Metrics to Define the Unique Dynamic Features
      of the Flap Regions Among Aspartic Proteases.
AB  - Aspartic proteases are a class of hydrolytic enzymes that have been implicated in
      a number of diseases such as HIV, malaria, cancer and Alzheimer's. The flap
      region of aspartic proteases is a characteristic unique structural feature of
      these enzymes; and found to have a profound impact on protein overall structure,
      function and dynamics. Flap dynamics also plays a crucial role in drug binding
      and drug resistance. Therefore, understanding the structure and dynamic behavior
      of this flap regions is crucial in the design of potent and selective inhibitors
      against aspartic proteases. Defining metrics that can describe the flap
      motion/dynamics has been a challenging topic in literature. This review is the
      first attempt to compile comprehensive information on sequence, structure, motion
      and metrics used to assess the dynamics of the flap region of different aspartic
      proteases in "one pot". We believe that this review would be of critical
      importance to the researchers from different scientific domains.

PMID- 28762199
TI  - Age-dependent alterations in serum cytokines, peripheral blood mononuclear cell
      cytokine production, natural killer cell activity, and prostaglandin F2alpha.
AB  - This study aimed to determine age-dependent alterations in serum cytokines,
      peripheral blood mononuclear cell (PBMC) cytokine production, natural killer (NK)
      cell activity, and urinary 8-epi-prostaglandin F2alpha (PGF2alpha). Nine hundred
      eighty-seven healthy and nonobese subjects were divided into five age groups: 20
      34 (group 1), 35-44 (group 2), 45-54 (group 3), 55-64 (group 4), and 65-80 (group
      5) years of age. After adjusting for BMI, sex, and smoking and drinking status,
      serum interferon (IFN)-gamma levels decreased in groups 3, 4, and 5 compared with
      those in groups 1 and 2. Production of IFN-gamma by unstimulated PBMCs was lower
      in the older groups (groups 4 and 5) than in the younger groups (groups 1 and 3).
      Serum interleukin (IL)-12 was lower in group 5 than in groups 1 and 2. In
      contrast, both serum and PBMC IL-6 were higher in group 5 than in groups 1, 2,
      and 3. Urinary 8-epi-PGF2alpha increased in group 3 compared with that in group 1
      and further increased in group 5. Multiple linear regression analysis revealed
      that serum IFN-gamma levels were negatively affected by age, and NK cell activity
      at a ratio of E:T = 5:1 was positively affected by PBMC IFN-gamma. This study
      shows the age-related reductions in serum and PBMC IFN-gamma and serum IL-12 and
      age-related increases in serum and PBMC IL-6 and oxidative stress in healthy
      nonobese subjects. Additionally, circulating IL-6 levels may be a better marker
      of the chronic low-grade inflammatory activity associated with aging than
      systemic levels of high-sensitivity C-reactive protein, TNF-alpha, and IL-1beta.

PMID- 28762200
TI  - Rapid-Acting and Human Insulins: Hexamer Dissociation Kinetics upon Dilution of
      the Pharmaceutical Formulation.
AB  - PURPOSE: Comparison of the dissociation kinetics of rapid-acting insulins lispro,
      aspart, glulisine and human insulin under physiologically relevant conditions.
      METHODS: Dissociation kinetics after dilution were monitored directly in terms of
      the average molecular mass using combined static and dynamic light scattering.
      Changes in tertiary structure were detected by near-UV circular dichroism.
      RESULTS: Glulisine forms compact hexamers in formulation even in the absence of
      Zn2+. Upon severe dilution, these rapidly dissociate into monomers in less than
      10 s. In contrast, in formulations of lispro and aspart, the presence of Zn2+ and
      phenolic compounds is essential for formation of compact R6 hexamers. These
      slowly dissociate in times ranging from seconds to one hour depending on the
      concentration of phenolic additives. The disadvantage of the long dissociation
      times of lispro and aspart can be diminished by a rapid depletion of the
      concentration of phenolic additives independent of the insulin dilution. This is
      especially important in conditions similar to those after subcutaneous injection,
      where only minor dilution of the insulins occurs. CONCLUSION: Knowledge of the
      diverging dissociation mechanisms of lispro and aspart compared to glulisine will
      be helpful for optimizing formulation conditions of rapid-acting insulins.

PMID- 28762201
TI  - Scanning Electron Microscope Observations of Powder Sticking on Punches during a
      Limited Number (N < 5) of Compactions of Acetylsalicylic Acid.
AB  - PURPOSE: To obtain quantitative information and mechanistic insight into the
      problem of sticking of acetylsalicylic acid tablets on a metallic punch. METHODS:
      Low voltage scanning electron microscopy was used to observe punch area coverage
      and morphology of adhered powder on a flat punch used for a limited number of
      compactions. RESULTS: Material accumulation in terms of area coverage of the
      punch per compaction cycle was determined at two pressures over five compactions.
      The distribution of the adhered material on the punch was non-uniform with more
      material left on the center of the punch. The sizes of the adhered particles
      range from 1 to 100 MUm, with 50% of the punch surface coverage from particles of
      an equivalent diameter > 30 MUm. Three types of adhered particles were identified
      after the first compaction: (a) fragments of initial particles with very high
      aspect ratio, (b) nearly equiaxed fragments with multiple cracks, (c) heavily
      deformed islands of low profile. Some preliminary ideas that explain these
      observations are presented and discussed. CONCLUSIONS: The ability of SEM to
      provide quantitative information on sticking from few compactions presents an
      interesting possibility for a material sparing technique that provides insight on
      the propensity of sticking.

PMID- 28762202
TI  - Verrucous herpes of the finger in a patient with HIV-1 infection.

PMID- 28762203
TI  - Power Color Doppler and Spectral Doppler Ultrasonography to Evaluate Response to
      Intra-articular Steroid Injection in Knee Joints in Juvenile Idiopathic
      Arthritis.
AB  - OBJECTIVE: To evaluate the role of ultrasonographic indices (Color Fraction and
      Resistive Index) in assessing the effect of intra-articular steroid (IAS)
      injection on synovial inflammation in knee joints of Juvenile Idiopathic
      Arthritis (JIA) patients and to determine the correlation between these
      ultrasonographic indices and clinical and laboratory parameters in JIA patients
      after IAS. METHODS: Twenty seven patients of JIA and equal number of age and sex
      matched healthy controls were enrolled. Thirty six knee joints were injected with
      IAS. Duration of morning stiffness, swelling score, tenderness score, range of
      motion, visual analogue scale for pain, Physician global assessment of disease
      activity, Patient/Parent assessment of general well being, Juvenile Arthritis
      Disease Activity Score, erythrocyte sedimentation rate (ESR), C-reactive protein
      (CRP), synovial thickness, synovial effusion, Color fraction (CF) and Resistive
      index (RI) were measured at base line and at one and two months of follow-up.
      RESULTS: At baseline, a significant difference was found in ESR, CRP, CF and RI
      values between cases and controls. A significant decrease in various clinical,
      core set variables and ultrasonographic parameters was observed at each follow
      up. Synovial thickness, synovial effusion and CF decreased by 51.78%, 64.67% and
      49.35% respectively and range of motion and RI increased by 166% and 31.94%
      respectively at second follow-up. Both CF and RI showed a significant correlation
      with active joint count. Both CF and RI had a high inter and intra-class
      correlation. CONCLUSIONS: Power Color Doppler and Spectral Doppler
      ultrasonographic indices (CF and RI) may have a role in assessment of the
      response to IAS injection of inflamed knee joints.

PMID- 28762204
TI  - Sentinel Lymph Node Characterization with a Dual-Targeted Molecular Ultrasound
      Contrast Agent.
AB  - PURPOSE: The purpose of this study was to assess the performance of molecular
      ultrasound with dual-targeted microbubbles to detect metastatic disease in the
      sentinel lymph nodes (SLNs) in swine model of naturally occurring melanoma. The
      SLN is the first lymph node in the lymphatic chain draining primary tumor, and
      early detection of metastatic SLN involvement is critical in the appropriate
      management of melanoma. PROCEDURE: Nine Sinclair swine (weight 3-7 kg; Sinclair
      BioResources, Columbia, MO, USA) with naturally occurring melanoma were examined.
      Siemens S3000 scanner with a 9L4 probe was used for imaging (Siemens
      Healthineers, Mountain View, CA). Dual-targeted contrast agent was created using
      Targestar SA microbubbles (Targeson, San Diego, CA, USA) labeled with
      alphanubeta3-integrin and P-selectin antibodies. Targestar SA microbubbles
      labeled with IgG-labeled were used as control. First, peritumoral injection of
      Sonazoid contrast agent (GE Healthcare, Oslo, Norway) was performed to detect
      SLNs. After that, dual-targeted and IGG control Targestar SA microbubbles were
      injected intravenously with a 30-min interval between injections. Labeled
      Targestar SA microbubbles were allowed to circulate for 4 min to enable binding.
      After that, two sets of image clips were acquired several seconds before and
      after a high-power destruction sequence. The mean intensity difference pre- to
      post-bubble destruction within the region of interest placed over SLN was
      calculated as a relative measure of targeted microbubble contrast agent
      retention. This process was repeated for non-SLNs as controls. All lymph nodes
      evaluated on imaging were surgically removed and histologically examined for
      presence of metastatic involvement. RESULTS: A total of 43 lymph nodes (25 SLNs
      and 18 non-SLNs) were included in the analysis with 18 SLNs demonstrating
      metastatic involvement greater than 5 % on histology. All non-SLNs were benign.
      The mean intensity (+/- SD) of the dual-targeted microbubbles for metastatic SLNs
      was significantly higher than that of benign LNs (18.05 +/- 19.11 vs. 3.30 +/-
      6.65 AU; p = 0.0008), while IgG-labeled control microbubbles demonstrated no
      difference in retained contrast intensity between metastatic and benign lymph
      nodes (0.39 +/- 1.14 vs. 0.03 +/- 0.24 AU; p = 0.14). CONCLUSIONS: The results
      indicate that dual-targeted microbubbles labeled with P-selectin and alphanubeta3
      integrin antibodies may aid in detecting metastatic involvement in SLNs of
      melanoma.

PMID- 28762205
TI  - Next-generation AAV vectors for clinical use: an ever-accelerating race.
AB  - During the past five decades, it has become evident that Adeno-associated virus
      (AAV) represents one of the most potent, most versatile, and thus most auspicious
      platforms available for gene delivery into cells, animals and, ultimately,
      humans. Particularly attractive is the ease with which the viral capsid-the major
      determinant of virus-host interaction including cell specificity and antibody
      recognition-can be modified and optimized at will. This has motivated countless
      researchers to develop high-throughput technologies in which genetically
      engineered AAV capsid libraries are subjected to a vastly hastened emulation of
      natural evolution, with the aim to enrich novel synthetic AAV capsids displaying
      superior features for clinical application. While the power and potential of
      these forward genetics approaches is undisputed, they are also inherently
      challenging as success depends on a combination of library quality, fidelity, and
      complexity. Here, we will describe and discuss two original, very exciting
      strategies that have emerged over the last three years and that promise to
      alleviate at least some of these concerns, namely, (i) a reverse genetics
      approach termed "ancestral AAV sequence reconstruction," and (ii) AAV genome
      barcoding as a technology that can advance both, forward and reverse genetics
      stratagems. Notably, despite the conceptual differences of these two
      technologies, they pursue the same goal which is tailored acceleration of AAV
      evolution and thus winning the race for the next-generation AAV vectors for
      clinical use.

PMID- 28762206
TI  - The retroviral vector family: something for everyone.
AB  - After 30 years of retroviral vector research it became clear that the parental
      viruses can be both friend and foe. Especially human immunodeficiency virus
      sparked a global pandemic, but could be converted into a versatile tool for cell
      therapy. For all retroviral genera, the way from virus to vector was similar
      resulting in split-vector systems based on the separation of the genes needed for
      vector particle formation and transgene expression. The first gene therapy
      trials, although clinically effective, revealed the genotoxicity of retroviral
      vectors caused by insertional mutagenesis. This issue was solved using self
      inactivating vectors carrying weaker cellular promoters. Further fine-tuning was
      able to generate inducible systems. The current toolbox also contains vectors for
      the generation of induced pluripotent stem cells or efficient RNA interference.
      More recently the application of CRISPR-Cas9-mediated gene editing led to the
      development of genome-wide small guide RNA libraries targeting all human genes
      and single lentiviral vectors for an easy delivery of Cas9.

PMID- 28762207
TI  - The efficacy of antisense-based construct for inducing resistance against Croton
      yellow vein mosaic virus in Nicotiana tabacum.
AB  - Begomoviruses have increased pathogenicity because of their adaptation to a wide
      host range; consequently, these viruses cause a major loss to agroeconomic crops
      worldwide. In this study, we designed a gene construct representing an antisense
      coat protein gene. We also analyzed the efficacy of the induced resistance
      against Croton yellow vein mosaic virus (CrYVMV) affecting papaya in Nicotiana
      tabacum plants. Positive control plants developed typical leaf curl symptoms,
      whereas transgenic plants were symptomless. Moreover, the key component (i.e.,
      short interfering RNA) of the antisense pathway was upregulated in transgenic
      plants. This finding demonstrates the activation of the gene silencing mechanism
      in transgenic plants. Thus, these results confirm that our construct is
      functional and effectively induces transient resistance against CrYVMV
      infections.

PMID- 28762208
TI  - Two novel poxviruses with unusual genome rearrangements: NY_014 and Murmansk.
AB  - The genome sequence and annotation of two novel poxviruses, NY_014 and Murmansk,
      are presented. Despite being isolated on different continents and from different
      hosts, the viruses are relatively similar, albeit distinct species. The closest
      known relative of the novel viruses is Yoka poxvirus. Five novel genes were found
      in these genomes, two of which were MHC class I homologs. Although the core of
      these genomes was well conserved, the terminal regions showed significant
      variability with large deletions and surprising evidence of recombination with
      orthopoxviruses.

PMID- 28762209
TI  - A Mapping Study on Mobile Games for Patients of Chronic Diseases.
AB  - There is a growing interest of using technologies to propose solutions for
      healthcare issues. One of such issues is the incidence of chronic diseases, which
      are responsible for a considerable proportion of worldwide mortality. It is
      possible to prevent the development of such diseases using tools and methods that
      instruct the population. To achieve this, mobile games provide a powerful
      environment for teaching different subjects to user, without them actively
      knowing that they are learning new concepts. Despite the growing interest of
      using mobile games in healthcare, more specifically by patients with chronic
      diseases, in the best of our knowledge there are no studies that address the
      current research being published in the area. To close this gap, we carried out a
      systematic mapping study to synthesize an overview of the area. Five databases
      were searched and more than 1200 studies were analyzed and filtered. Among them,
      17 met the the inclusion and exclusion criteria defined in this work. The results
      show that there is still room for research in this area, since the studies focus
      on a younger audience rather than proposing solutions for all ages. Furthermore,
      the number of chronic conditions being addressed is still small, obesity and
      diabetes are prevalent. Besides, the full capacity of game features that foster
      learning through games are not being employed, the majority of games proposed by
      the articles encompass less than half of these features.

PMID- 28762210
TI  - Association between the severity of symptomatic knee osteoarthritis and
      cumulative metabolic factors.
AB  - BACKGROUND: The association between cumulative metabolic syndrome (MS) factors
      and knee osteoarthritis (KOA) has been highlighted over the past two decades.
      AIMS: To clarify the relationship between cumulative MS factors and symptomatic
      KOA. METHODS: A cross-sectional survey involving 119 women aged 45-88 years who
      were scheduled to undergo knee surgery was conducted. They were stratified into
      tertiles of symptoms as assessed by the Japanese Orthopedic Association score for
      KOA. Multinomial logistic regressions were performed using the severity of
      symptomatic KOA as the dependent variable and each MS factor or the cumulative MS
      factors as the independent variables. RESULTS: Logistic regression analyses were
      performed with the upper tertile of stratified symptoms of subjects used as the
      reference group. After adjustment for confounders, KOA patients who had two (p =
      0.004) or three or more (p < 0.0001) MS factors were significantly more likely to
      have severe symptoms compared to those who had no MS factors. MS factors
      excluding obesity were similarly analyzed. Even after additional adjustment for
      body mass index (BMI), KOA patients who had two or more (p = 0.005) MS factors
      were significantly more likely to have severe symptoms. CONCLUSION: Among KOA
      female patients diagnosed using radiographic definition, the severity of
      symptomatic KOA was significantly associated with hypertension, dyslipidemia, and
      the number of MS factors after adjustment for age, BMI, strength of the knee
      extensor, and Kellgren-Lawrence grade. The severity of radiographic KOA was not
      associated with any MS factor or cumulative MS factors.

PMID- 28762211
TI  - Low prevalence of atrial fibrillation in Amerindians: a population-based study in
      frequent fish consumers living in rural coastal Ecuador (The Atahualpa Project).
AB  - BACKGROUND: Information on the burden of atrial fibrillation (AF) in rural areas
      of developing countries is limited. Here, we aimed to assess AF prevalence in
      community-dwelling older adults living in rural Ecuador. METHODS: Atahualpa
      residents aged >=60 years (mean age 70.5 +/- 8.1 years) underwent 24-h Holter
      monitoring. Participants belong to the Amerindian ethnic group. The mean height
      in the study population was 147.9 +/- 8.9 cm. Oily fish was a major source of
      food (mean intake: 8 +/- 4 servings/week). RESULTS: Seven of 298 participants
      (2.3%) had AF. Persons with AF were older than those without (p = 0.051), but
      there were no differences in cardiovascular risk factors across groups. None of
      the seven AF cases had been detected in routine 12-lead ECGs taken at enrollment.
      CONCLUSIONS: Prevalence of AF in older Amerindians living in rural Ecuador is
      low. Both, racially-determined short stature and frequent dietary oily fish
      intake might explain the low prevalence of AF in this rural setting.

PMID- 28762212
TI  - Experimental Studies and Modeling of the Drying Kinetics of Multicomponent
      Polymer Films.
AB  - The process of drying thin polymer films is an important operation that
      influences the film structure and solid state, and the stability of the product.
      The purpose of this work was to study and model the drying kinetics of
      multicomponent films based on two polymers: hydroxypropyl methylcellulose (HPMC,
      amorphous) and polyvinyl alcohol (PVA, semicrystalline). The isothermal drying
      kinetics of the films at different temperatures (40, 60, and 80 degrees C) were
      studied using thermo-gravimetric analysis (TGA) and convection oven methods.
      Solid-state characterization tools used in the study included polarization and
      hot-stage microscopy, scanning electron microscopy (SEM), and differential
      scanning calorimetry (DSC). The drying kinetics of HPMC and PVA films in the TGA
      apparatus and convection oven were comparable. The three-parameter (W max, tau,
      n) Hill equation successfully modeled the experimental drying kinetics. The time
      factor tau in the Hill equation nicely explained two drying phases in the films.
      Solid-state phase changes occurring in the films during dehydration had a bearing
      on the drying kinetics and mechanisms. TGA can be used as a simple tool to
      determine the end points in drying processes using ovens or tunnels. The three
      parameter Hill equation explained the drying kinetics and diffusion mechanisms of
      the solvent through the polymer films for the first time. This study advances our
      understanding of film drying, in particular for pharmaceutically relevant thin
      films.

PMID- 28762213
TI  - Comparative Effectiveness of Adalimumab versus Secukinumab for the Treatment of
      Psoriatic Arthritis: A Matching-Adjusted Indirect Comparison.
AB  - INTRODUCTION: The Phase III FUTURE I and II trials demonstrated the clinical
      efficacy of secukinumab in active psoriatic arthritis (PsA). In the absence of
      head-to-head trials, this study compared the clinical efficacy and cost
      effectiveness of adalimumab 40 mg versus secukinumab 150 and 300 mg for the
      treatment of active PsA. METHODS: A matching-adjusted indirect comparison was
      conducted using individual patient data from the ADEPT trial of adalimumab and
      published data from FUTURE I and II. To adjust for the cross-trial differences,
      individual patients in ADEPT were re-weighted so that the mean baseline
      characteristics (including age, weight, gender, race, baseline methotrexate use,
      psoriasis >=3% body surface area, baseline PASI score, presence of dactylitis and
      enthesitis, and HAQ-DI) matched those in the FUTURE trials. Response rates
      relative to placebo and incremental costs per responder (CPR) over 24 weeks for
      ACR 20/50/70 and PASI 75/90 were compared between adalimumab and secukinumab 150
      and 300 mg from the German social health insurance (SHI) perspective. RESULTS:
      After matching, mean baseline characteristics were balanced across the ADEPT and
      the FUTURE I and II populations. The mean differences between adalimumab and
      secukinumab 150 mg in relative ACR 20/50/70 and PASI 75/90 response rates were
      9.5, 3.0, 6.0, 13.1, and 6.7%, respectively (p > 0.05 for all comparisons). Post
      match relative ACR 20/50/70 and PASI 75 to placebo were also higher with
      adalimumab compared to secukinumab 300 mg. Adalimumab had lower incremental costs
      per responder over 24 weeks for all outcomes compared with secukinumab 150 and
      300 mg. CONCLUSIONS: In the absence of direct comparisons between adalimumab and
      secukinumab, this study provides valuable and reliable evidence for physicians
      and payers. After adjusting for cross-trial differences in baseline
      characteristics, adalimumab was associated with higher relative ACR and PASI
      rates and lower incremental CPRs compared with secukinumab 150 mg or 300 mg at
      week 24 among patients with active PsA. FUNDING: AbbVie.

PMID- 28762214
TI  - Economic "Activity-Silent" Synaptic Mechanisms of Working Memory.

PMID- 28762215
TI  - Tiny But Mighty: Promising Roles of MicroRNAs in the Diagnosis and Treatment of
      Parkinson's Disease.
AB  - Parkinson's disease (PD) is the second most common age-related neurodegenerative
      disorder after Alzheimer's disease. To date, the clinical diagnosis of PD is
      primarily based on the late onset of motor impairments. Unfortunately, at this
      stage, most of the dopaminergic neurons may have already been lost, leading to
      the limited clinical benefits of current therapeutics. Therefore, early
      identification of PD, especially at the prodromal stage, is still a main
      challenge in the diagnosis and management of this disease. Recently, microRNAs
      (miRNAs) in cerebrospinal fluid or peripheral blood have been proposed as
      putative biomarkers to assist in PD diagnosis and therapy. In this review, we
      systematically summarize the changes of miRNA expression profiles in PD patients,
      and highlight their putative roles in the diagnosis and treatment of this
      devastating disease.

PMID- 28762217
TI  - Acute Toxicity and Sublethal Effects of Terpenoids and Essential Oils on the
      Predator Chrysoperla externa (Neuroptera: Chrysopidae).
AB  - The search for new safer insecticides has increased in recent agriculture.
      Botanical compounds such as terpenoids and plant essential oils with insecticidal
      activity could represent important tools in pest management, and their risk
      assessment against non-target organisms is necessary since they may serve as a
      precursor for the synthesis of new insecticide active ingredients. For this
      study, the acute toxicity and sublethal effects of seven terpenoids and three
      essential oils with recognized insecticidal activity were evaluated on the
      predator Chrysoperla externa (Hagen) (Neuroptera: Chrysopidae) in laboratory
      bioassays. Results indicate that these compounds feature relative selectivity to
      the predator C. externa; however, sublethal effects on reproduction were recorded
      for some compounds. The phenolic monoterpenoids carvacrol and thymol were more
      acutely toxic than other terpenoids screened, with LD50 <20,000 MUg/g; however,
      they were less toxic than natural pyrethrins (toxicity standard) in these
      bioassays. Sublethal effects on fecundity and fertility were observed for R-(+)
      limonene, while oregano oil only affected fecundity. The compounds evaluated here
      have potential to be used as insecticides and can serve as backbone for future
      synthesis of selective active ingredients; however, a complete risk assessment to
      C. externa and other non-target organisms is necessary for their incorporation in
      future crop protection paradigms.

PMID- 28762216
TI  - Age-specific reference interval of serum TSH levels is high in adolescence in an
      iodine excess area: Korea national health and nutrition examination survey data.
AB  - PURPOSE: Serum thyroid-stimulating hormone level was influenced by several
      factors, including age, gender, thyroid auto-antibodies, race, and intake of
      dietary iodine. We evaluated age-specific reference interval of serum thyroid
      stimulating hormone levels in Korea, an iodine excess area. METHODS: This
      nationwide population-based cross-sectional study included representative
      civilian, non-institutional population (n = 6564) who underwent thyroid function
      tests from Korea National Health and Nutrition Examination Survey VI (2013-2015).
      The reference interval of serum thyroid-stimulating hormone levels was defined
      between the 2.5th and 97.5th percentiles in the reference population. RESULTS:
      The geometric mean of serum thyroid-stimulating hormone levels in the reference
      population was 2.17 mIU/L with a reference interval of 0.62-6.84 mIU/L. In the
      reference population, the geometric mean of serum TSH levels in each age group of
      10-18, 19-29, 30-39, 40-49, 50-59, 60-69, and equal or older than 70 years was
      2.47, 2.20, 2.07, 2.04, 2.23, 2.12, and 2.27 mIU/L, with a reference interval of
      0.74-7.35, 0.67-6.42, 0.63-6.04, 0.62-6.20, 0.56-7.37, 0.57-6.90, and 0.42-6.58
      mIU/L, respectively. In the reference population, the urinary iodine
      concentrations were consistently high in all age groups (median 298.5 MUg/L).
      Subjects aged 10-18 years had the highest urinary iodine concentrations.
      CONCLUSIONS: There was no shift toward higher levels with age in the distribution
      of serum thyroid-stimulating hormone levels. The reference interval of serum
      thyroid-stimulating hormone levels was consistently high in all age group,
      especially from adolescence 10-18 years in a Korean population who had excessive
      intake of dietary iodine.

PMID- 28762218
TI  - Para-Quinodimethanes: A Unified Review of the Quinoidal-Versus-Aromatic
      Competition and its Implications.
AB  - In this article, some quinoidal p-quinodimethanes compounds that convert
      partially or completely to diradicals or biradicaloids are analyzed. The
      aromatic/quinoidal balance is revisited with the objective of providing a common
      interpretation for most of them. For that purpose, important structural and
      energetic parameters such as the bond length alternation pattern and the singlet
      triplet gaps are analyzed and interpreted in the framework of double spin
      polarization and pi-conjugation. p-Quinodimethanes based in oligothiophenes,
      polycyclic aromatic hydrocarbons, oligophenylenes, thienothiophenes, charged
      dications and cyclic conjugated molecules are discussed. There are excellent
      reviews in the field of singlet diradicals; however, a revision similar to that
      proposed here can help the reader to have another perspective on these promising
      new functional materials. The focus has been put on molecules which are well
      known by the author and another of relevance in the field. In this regard, the
      article finishes with a discussion of some important applications of these
      diradicals in organic electronics. New chemical systems based on the p
      quinodimethane building blocks are waiting us around the corner, bringing us new
      and challenging structures and fascinating novel properties, which describe a
      very rich field of research in chemistry and in physics with an excellent present
      and a bright future.

PMID- 28762219
TI  - [The Role and Function of Informatics Nurses in Information Technology Decision
      Making].
AB  - The medical environment has changed greatly with the coming of the information
      age, and, increasingly, the operating procedures for medical services have been
      altered in keeping with the trend toward mobile, paperless services.
      Informatization has the potential to improve the working efficiency of medical
      personnel, enhance patient care safety, and give medical organizations a positive
      image. Informatics nurses play an important role in the decision-making processes
      that accompany informatization. As one of the decision-making links in the
      information technology lifecycle, this role affects the success of the
      development and operation of information systems. The present paper examines the
      functions and professional knowledge that informatics nurses must possess during
      the technology lifecycle, the four stages of which include: planning, analysis,
      design/development/revision, and implementation/assessment/support/maintenance.
      The present paper further examines the decision-making shortcomings and errors
      that an informatics nurses may make during the decision-making process. We hope
      that this paper will serve as an effective and useful reference for informatics
      nurses during the informatization decision-making process.

PMID- 28762220
TI  - [The Development of an Intelligent Long-Term Care Services System That Integrates
      Innovative Information and Communication Technologies].
AB  - Rapid progress in information and communication technologies and the increasing
      popularity of healthcare-related applications has increased interest in the topic
      of intelligent medical care. This topic emphasizes the use of information and
      communication technologies to collect and analyze a variety of data in order to
      provide physicians and other healthcare professionals with clinical decision
      support. At present, so-called smart hospitals are the focal point of most
      intelligent-systems development activity, with little attention currently being
      focused on long-term care needs. The present article discusses the application of
      intelligent systems in the field of long-term care, especially in community and
      home-based models of care. System-implementation components such as the data
      entry interface components of mobile devices, the data transmission and
      synchronization components between the mobile device and file server, the data
      presentation, and the statistics analysis components are also introduced. These
      components have been used to develop long-term care service-related applications,
      including home health nursing, home-care services, meals on wheels, and assistive
      devices rental. We believe that the findings will be useful for the promotion of
      innovative long-term care services as well as the improvement of healthcare
      quality and efficiency.

PMID- 28762221
TI  - [The Utilization of Health-Related Applications in Chronic Disease Self
      Management].
AB  - The dramatic increase in smartphone usage has spurred the development of many
      health-related mobile applications (apps). On the other hand, population aging
      and the associated rise in the incidence of chronic disease is increasing the
      demand for long-term care. Effective chronic disease self-management has been
      shown to help patients improve their health condition. Numerous smartphone
      applications currently support patient self-management of chronic disease,
      facilitating health management and health promotion. The purpose of the present
      article was to introduce the definition, contents, and types of health-related
      apps; to discuss the effectiveness of self-management health-related apps in
      promoting chronic disease management; and to assess and evaluate these apps. We
      hope that the present article helps give to healthcare professionals and patients
      who are willing to manage their diseases a general understanding of health
      related apps and their potential to facilitate the self-management of chronic
      diseases.

PMID- 28762222
TI  - [Smart Medicine and Healthcare].
AB  - Innovation and rapid technological development in Smart Medicine or Smart
      Healthcare impact profoundly on many aspects of healthcare. It is believed that
      Health Information Technology (HIT) has the potential to improve integration
      between care providers, reduce administrative costs and burdens, reduce medical
      errors, and improve care quality and patient outcomes. However, issues such as
      interoperability, compatibility, and integration are critical to effectively
      integrating hardware and software in order to fully realize the benefits of HIT.
      High-end medical devices and equipment, including medical carts / mobile computer
      carts and wireless physiological and biomedical monitoring devices, should also
      be integrated into the hospital information system. Furthermore, the Data,
      Information, Knowledge, and Wisdom Hierarchy (DIKW) has been gaining popularity
      in the development of Nursing Information Systems (NIS) since 2013. To create a
      DIKW-based information system, data must first be defined and analyzed and then
      transformed into meaningful information. Eventually, this information is
      transformed into an intelligent system. For example, if evidence-based nursing
      research results / findings are integrated into the NIS to guide clinical
      practice, patient outcomes, patient safety, and healthcare quality will be
      greatly enhanced.

PMID- 28762223
TI  - [Factors Associated With Successful Smoking Cessation in Male Patients With
      Coronary Artery Disease at 3 Months After Hospital Discharge].
AB  - BACKGROUND: The promising effects of smoking cessation for coronary artery
      disease (CAD) patients include decreased risks of subsequent clinical events and
      mortality. However, most CAD patients continue to smoke after being hospitalized
      for a cardiac event. PURPOSE: To explore the factors that are associated with
      successful smoking cessation in CAD male patients at 3 months after hospital
      discharge. METHODS: A correlational design was applied. A convenience sample (N =
      165) was recruited from the cardiac wards of two medical centers in northern
      Taiwan and 154 of these completed the 3-month follow up. The medical charts of
      the participants were reviewed to obtain their disease-related factors. All of
      the participants finished one questionnaire during their hospital stay. This
      questionnaire collected data on participant demographics, smoking and quitting
      history, and nicotine addiction as well as the causal attribution of heart
      disease to smoking, importance of smoking outcomes, self-efficacy for quitting,
      and post-discharge intention to quit. Information on post-discharge smoking
      status was collected via phone calls to the participants at three-months after
      hospital discharge and, for participants who claimed to have not smoked since
      discharge, was further confirmed by measuring their expired CO (carbon monoxide)
      level. Multiple logistic regression analysis was used to examine the identified
      predictors of successful smoking cessation. RESULTS: The 3-month self-reported
      rate of abstinence was 37.01% (n = 57), while the rate of abstinence as confirmed
      by expired CO was 31.17% (n = 48). Those with acute coronary syndrome, longer
      hospital stays, and higher post-discharge intention to quit were more likely to
      quit smoking. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The abstinence rate as
      confirmed by expired CO for hospitalized male patients with CAD is more accurate
      than the rate obtained by self-reporting. Healthcare providers should stress the
      importance of smoking cessation, especially for those who have been diagnosed
      with angina, are hospitalized for shorter periods of time, and indicate a lower
      post-discharge intention to abstinence.

PMID- 28762224
TI  - [Factors and Medical Costs Associated With Fall Events in Hospitalized Patients].
AB  - BACKGROUND: Patient falls are a common, adverse event in hospitals that may
      result in economic and care burdens on the patient and his/her family afterward.
      PURPOSE: To analyze the factors that relate to falls among inpatients and to
      estimate the associated days of hospitalization and medical costs. METHODS: The
      present study used a retrospective matched case-control design to analyze
      inpatient fall data for 2009 to 2011 from a regional teaching hospital in
      northern Taipei. We matched fallers and controls according to gender, age ? 5
      years, and ICD-9-CM (International Classification of Diseases, Ninth Revision,
      Clinical Modification) code. Data were analyzed using descriptive and inferential
      statistics. RESULTS: A total of 160 inpatients participated in the present study
      (80 fallers in the fall group and 80 nonfallers in the control group). The
      results revealed that fallers had more previous fall experiences and longer
      hospital stay than nonfallers. Multiple logistic regression analysis revealed
      that the risk factors that were significantly associated with inpatient falls
      included: no family accompaniment, use of more than 3 fall-related medications,
      and no intravenous catheter placement. Results further found that medical costs
      increased with the degree of injury. Third-degree injuries bore the highest post
      fall medical costs of all of the injury-degree categories. The average medical
      cost for patients with third-degree injuries was 18,257 New Taiwan dollars.
      CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The findings provide a reference for
      hospitals to promote patient safety, to prevent the occurrence of inpatient
      falls, and, ultimately, to reduce fall-associated medical costs.

PMID- 28762225
TI  - [Psychometric Characteristics of the Clinical Nursing Mentors' Behavior Scale].
AB  - BACKGROUND: The behavior of mentors impacts the quality and experience of nursing
      students who are studying in clinical placement. Accurately assessing the
      behavior of mentors is fundamental to training, regulating, guiding, and
      improving their behavior and quality of teaching. PURPOSE: To test the validity
      and reliability of the Clinical Nursing Mentors' Behavior Scale (CNMBS) among
      mentors. METHODS: This study included three stages. During the first stage, seven
      Chinese experts were invited to evaluate content validity. During the second
      stage, the test-retest reliability was examined with 63 mentors. During the third
      stage, a cross-sectional study was conducted. Seven hundred and sixty-six nursing
      mentors from five hospitals in Beijing, Shenzhen, and Sichuan completed the
      survey either online or in hard copy form. The data collected from the
      questionnaire were analyzed using item analysis, construct validity, internal
      consistency and discriminant validity, with the results used to determine the
      psychometric characteristics of the CNMBS. RESULTS: The content validity index
      for the CNMBS was .91. The intra-class correlation coefficient was .89; the range
      of the item discrimination critical ratio was 9.42-22.43 (p < .001), and the item
      total correlation was .35- .70 (p < .001). The three factors of "guiding personal
      growth", "promoting professional development", and "providing psychosocial
      support" and a total of 23 items were identified, with item factor loadings
      ranging from .51 to .79. The three factors explained 50.99% of total variance.
      The internal consistency of the CNMBS earned a Cronbach's alpha coefficient of
      .92, while those of the three subscales were .89, .86 and .75, respectively.
      CONCLUSIONS: The Clinical Nursing Mentors' Behavior Scale demonstrated high
      validity and reliability, supporting the CNMBS as a valid tool for assessing the
      teaching behavior of mentors.

PMID- 28762227
TI  - [Chlorhexidine Bed-Bath Improves CLABSI: A Meta-Analysis].
AB  - BACKGROUND: Central catheters are used primarily in ICU settings. Bloodstream
      infections in the central line of central catheters have been shown to cause
      longer hospital stays for patients and result in higher medical costs. PURPOSE:
      The present study applies a systematic review and meta-analysis to assess the
      effect of a 2% chlorhexidine (CHG) bed-bath on the risk of central line
      associated bloodstream infections (CLABSI). METHODS: The Public Health Resource
      Unit of England issued the Critical Appraisal Skills Programme and evaluated the
      standardized crucial appraisal tools from the Joanna Briggs Institute that are
      used to assess methodological quality. The present study identified 6 studies
      that met the criteria from a keyword search that included: CHG and soap-water for
      bed-bath experiment. The experiment used RevMan 5 software to conduct the meta-
      analysis. RESULTS: The results support the homogeneity (p = .002, I2 = 64%) of
      the sample. Comprehensive effectiveness was 0.45 (95% CI [0.35, 0.58], p < .001).
      The CHG bed-bath intervention was shown to effectively reduce CLABSI. CONCLUSIONS
      / IMPLICATIONS FOR PRACTICE: The meta-analysis indicated that bed-bath with CHG
      reduces the incidence of CLABSI. We recommend that center catheter bundle care be
      applied in ICUs in combination with CHG bed-bath in order to reduce the risk of
      CLABSI.

PMID- 28762226
TI  - [The Effectiveness of Cooling Packaging Care in Relieving Chemotherapy-Induced
      Skin Toxicity Reactions in Cancer Patients Receiving Chemotherapy: A Systematic
      Review].
AB  - BACKGROUND: Anti-cancer chemotherapy may cause skin-toxicity reactions. Different
      types of cooling packages affect chemotherapy-induced skin toxicity reactions
      differently. PURPOSE: To evaluate the effects of cooling packing care on
      chemotherapy-induced skin toxicity reactions in cancer patients receiving
      chemotherapy. METHODS: A systematic review approach was used. Searches were
      conducted in databases including Cochrane Library, Embase, MEDLINE, PubMed and
      Airiti Library using the keywords "chemotherapy cutaneous toxicity",
      "chemotherapy skin reaction", "chemotherapy skin toxicity", "frozen glove",
      "frozen sock", "cooling packaging care", "ice gloves", "ice socks", "usual care",
      "severity", "comfort", "satisfaction", "severity", and "comfort". The search
      focused on articles published before December 2016. Based on the inclusion and
      exclusion criteria, 5 articles involving relevant randomized controlled trials
      were extracted for review. RESULTS: Elasto-Gel ice gloves or ice socks that were
      chilled to -25 degrees C- -30 degrees C and used for 15 mins during initial
      chemotherapy, for one hour during chemotherapy infusion, and for 15 mins after
      chemotherapy were shown to improve the frequency and severity of chemotherapy
      induced skin toxicity reactions. Several studies were limited by small sample
      sizes and different types of cooling packing programs, temperature, timing, and
      frequency. Thus, further research is recommended to verify the effects of cooling
      packing care. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Cancer patients who were
      treated with docetaxel or PLD and who used ice gloves or ice socks that were
      chilled to -25 degrees C- -30 degrees C for 15 mins during initial chemotherapy,
      for one hour during chemotherapy infusion, and for 15 mins after chemotherapy
      improved significantly in terms of the frequency and severity of their
      chemotherapy-induced skin toxicity reactions. Local cooling packing care is a non
      pharmacotherapy approach that is low cost and free of side effects. This review
      is intended to provide a reference for clinical care.

PMID- 28762228
TI  - [A Systematic Review and Meta-Analysis of the Pros and Cons of Consuming Liquids
      Preoperatively].
AB  - BACKGROUND: Preoperative anesthesia long time fasting, may increase patient
      hemodynamic instability during surgery and may affect the patient's post-surgery
      electrolyte balance. No meta-analysis has been conducted to explore the effects
      of preoperative liquid intake amount on gastric fluid PH, gastric fluid volume,
      surgery inhalation of pulmonary complications, and patient self-perceptions
      quality of care systematic review and meta-analysis of the literature. PURPOSE:
      To assess the pros and cons of preoperative liquid intake using a systematic
      review of the literature. METHODS: The authors searched ten databases including
      NRC (Nursing Reference Center), CINAHL (Cumulative Index to Nursing and Allied
      Health Literature), WOS (Web of Science), PubMed, The Cochrane Library, UpToDate,
      DynaMed, NGC (National Guideline Clearinghouse), Airiti Library, and National
      Digital Library of Theses and Dissertations in Taiwan, to identify relevant
      articles that were published from 2003 to January 2017. Nine qualified articles
      were included in the analysis from the 30 articles that were selected using an
      initial keyword search. The Oxford Centre for Evidence-based Medicine 2011 Levels
      of Evidence was used as the evidence grade and the CASP (Critical Appraisal
      Skills Program) was used to evaluate the quality of the selected articles. The
      quantitative results were analyzed using Review Manager, Version 5.1. RESULTS:
      The quality of the literature was medium to high. A small to moderate dose of
      fluid consumed at 2 hours prior to surgery did not significantly increase gastric
      fluid volume during anesthesia, with a combined effect of 2.37 (95% CI [-5.12,
      9.85], p = .54), and had no effect on gastric fluid PH, with a combined effect of
      0.10 (95% CI [0.00, 0.20], p = .05). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The
      results indicate that consuming a small to moderate dose of liquid at 2 hours
      prior to the provision of anesthesia does not significantly increase the gastric
      fluid volume or gastric fluid PH of patients during anesthesia. Moreover, the
      positive benefits of consuming this dose of liquid include reduced risks of
      aspiration pneumonia, gastroesophageal reflux disease, and postoperative
      complications as well as reduced perceptions of thirst and hunger during the
      immediate preoperative period. Thus, this analysis supports that the advantages
      of allowing patients to consume a moderate or smaller dose of liquid prior to
      surgery outweigh the disadvantages.

PMID- 28762229
TI  - [Percutaneous Edge-to-Edge Mitral Valve Repair: New Transcatheter Approach and
      Nursing Experience in Patients With Severe Mitral Regurgitation and Prohibitive
      Surgical Risk].
AB  - Open-heart surgery and conservative medical treatments have been the traditional,
      mainstay treatments for patients with severe mitral regurgitation (MR).
      Transcatheter edge-to-edge mitral repair is a novel technique. Using the
      transcatheter approach allows delivery of the clip into the left ventricle and
      the clipping of the orifice of the MR. The heart failure symptoms and outcomes of
      patients improve after this procedure. Compared to open-heart surgery, the mitral
      clip achieves similar MR reduction results with a significantly lower rate of
      complications. Since 2016, MitraClip has been available for clinical use in
      Taiwan. The aim of this report is to introduce this new treatment with a focus on
      nursing care in order to provide a reference for clinical care.

PMID- 28762230
TI  - [The Application of Mindfulness in Promoting Happiness and Mental Health].
AB  - Happiness, an important factor in maintaining health, not only enhances the
      abilities of self-control, self-regulation, and coping but also promotes mental
      health. Mindfulness therapy has been increasingly used in recent years.
      Therefore, the purpose of the present article is to introduce the concepts of
      mindfulness and to describe the relationship between mindfulness and happiness.
      Further, we provide brief introductions to mindfulness-based stress reduction and
      mindfulness cognitive therapy as well as present the current evidence related to
      the effects of mindfulness programs and therapies in clinical patient care. The
      information in the present article may be referenced and used by nurses in
      patient care and may be referenced by health professionals to promote their own
      mental health in order to maintain optimal fitness for providing high-quality
      patient care.

PMID- 28762231
TI  - [Nursing Experience Applying a Bereavement Counseling Model on an Elderly Patient
      With Depression].
AB  - Grief counseling is an effective treatment for those who have experienced a loss.
      In this case study, therapeutic communication was used as part of a nursing
      intervention to assist an elderly patient with depression to overcome grief and
      continue with life. The stage-based Four Tasks of Mourning proposed by William
      Worden were employed. These tasks include: (1) accepting the reality of the loss;
      (2) working through the pain of grief; (3) adjusting to a new environment without
      the deceased; and (4) focusing attention on other relationships. The nursing
      intervention occurred between December 14, 2015 and February 3, 2016. During this
      period, the author offered grief counseling to help the subject endure the loss
      of their kin, express their grief and pain, overcome difficulties in making
      adjustments, and move on from the loss by developing new life goals. The subject
      eventually acknowledged the irreversibility of what had happened and accepted the
      death through self-reacceptance and the support of friends and family. The
      patient was thus able to overcome his grief-induced behavior patterns, and
      rekindle his hopes for life and existing relationships. Therefore, the author
      recommends that nursing personnel assess carefully the reactions of elderly
      patients with depression to loss and provide adequate grief counseling that helps
      them fulfill the tasks of mourning.

PMID- 28762232
TI  - Morphofunctional basis of the different types of angiogenesis and formation of
      postnatal angiogenesis-related secondary structures.
AB  - We review the morpho-functional basis of the different types of angiogenesis and
      report our observations, including the formation of angiogenesis-related
      secondary structures. First of all, we consider the following issues: a)
      conceptual differences between angiogenesis and vasculogenesis, b) incidence of
      angiogenesis in pre- and postnatal life, c) regions of vascular tree with
      angiogenic capacity, d) cells (endothelial cells, pericytes, CD34+ adventitial
      stromal cells of the microvasculature and inflammatory cells) and extracellular
      matrix components involved in angiogenesis, e) events associated with
      angiogenesis, f) different types of angiogenesis, including sprouting and
      intussusceptive angiogenesis, and other angiogenic or vascularization forms
      arising from endothelial precursor cells (postnatal vasculogenesis),
      vasculogenesis mimicry, vessel co-option and piecemeal angiogenesis.
      Subsequently, we consider the specific morpho-functional characteristics of each
      type of angiogenesis. In sprouting angiogenesis, we grouped the events in three
      phases: a) activation phase, which includes vasodilation and increased
      permeability, EC, pericyte and CD34+ adventitial stromal cell activation, and
      recruitment and activation of inflammatory cells, b) sprouting phase,
      encompassing EC migration (concept and characteristics of endothelial tip cells,
      tip cell selection, lateral inhibition, localized filopodia formation, basal
      lamina degradation and extracellular changes facilitating EC migration), EC
      proliferation (concept of endothelial stalk cells), pericyte mobilization,
      proliferation, recruitment and changes in CD34+ adventitial stromal cells and
      inflammatory cells, tubulogenesis, formation of a new basal lamina, and vascular
      anastomosis with capillary loop formation, and c) vascular remodelling and
      stabilization phase (concept of phalanx cells). Subsequently, the concept,
      incidence, events and mechanisms are considered in the other forms of
      angiogenesis. Finally, we contribute the formation of postnatal angiogenesis
      related secondary structures: a) intravascular structures through piecemeal
      angiogenesis, including intravascular papillae in vessel tumours and
      pseudotumours (intravascular papillary endothelial hyperplasia, vascular
      transformation of the sinus in lymph nodes, papillary intralymphatic
      angioendothelioma or Dabska tumour, retiform hemangioendothelioma,
      hemangiosarcoma and lymphangiosarcoma), vascular septa in hemorrhoidal veins and
      intravascular projections in some tumours; b) arterial intimal thickening; c)
      intravascular tumours and pseudotumours (e.g. intravenous pyogenic granulomas and
      intravascular myopericytoma); d) vascular glomeruloid proliferations; and e)
      pseudopalisading necrosis in glioblastoma multiform.

PMID- 28762233
TI  - The disconnect between the science on cannabis and public health campaigns.

PMID- 28762235
TI  - Fluid supplementation for neonatal unconjugated hyperbilirubinaemia.
AB  - BACKGROUND: Neonatal hyperbilirubinaemia is a common problem which carries a risk
      of neurotoxicity. Certain infants who have hyperbilirubinaemia develop bilirubin
      encephalopathy and kernicterus which may lead to long-term disability.
      Phototherapy is currently the mainstay of treatment for neonatal
      hyperbilirubinaemia. Among the adjunctive measures to compliment the effects of
      phototherapy, fluid supplementation has been proposed to reduce serum bilirubin
      levels. The mechanism of action proposed includes direct dilutional effects of
      intravenous (IV) fluids, or enhancement of peristalsis to reduce enterohepatic
      circulation by oral fluid supplementation. OBJECTIVES: To assess the risks and
      benefits of fluid supplementation compared to standard fluid management in term
      and preterm newborn infants with unconjugated hyperbilirubinaemia who require
      phototherapy. SEARCH METHODS: We used the standard search strategy of Cochrane
      Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL;
      2017, Issue 5), MEDLINE via PubMed (1966 to 7 June 2017), Embase (1980 to 7 June
      2017), and CINAHL (1982 to 7 June 2017). We also searched clinical trials
      databases, conference proceedings, and the reference lists of retrieved articles
      for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA:
      We included randomised controlled trials that compared fluid supplementation
      against no fluid supplementation, or one form of fluid supplementation against
      another. DATA COLLECTION AND ANALYSIS: We extracted data using the standard
      methods of the Cochrane Neonatal Review Group using the Covidence platform. Two
      review authors independently assessed the eligibility and risk of bias of the
      retrieved records. We expressed our results using mean difference (MD), risk
      difference (RD), and risk ratio (RR) with 95% confidence intervals (CIs). MAIN
      RESULTS: Out of 1449 articles screened, seven studies were included. Three
      articles were awaiting classification, among them, two completed trials
      identified from the trial registry appeared to be unpublished so far.There were
      two major comparisons: IV fluid supplementation versus no fluid supplementation
      (six studies) and IV fluid supplementation versus oral fluid supplementation (one
      study). A total of 494 term, healthy newborn infants with unconjugated
      hyperbilirubinaemia were evaluated. All studies were at high risk of bias for
      blinding of care personnel, five studies had unclear risk of bias for blinding of
      outcome assessors, and most studies had unclear risk of bias in allocation
      concealment. There was low- to moderate-quality evidence for all major
      outcomes.In the comparison between IV fluid supplementation and no
      supplementation, no infant in either group developed bilirubin encephalopathy in
      the one study that reported this outcome. Serum bilirubin was lower at four hours
      postintervention for infants who received IV fluid supplementation (MD -34.00
      MUmol/L (-1.99 mg/dL), 95% CI -52.29 (3.06) to -15.71 (0.92); participants = 67,
      study = 1) (low quality of evidence, downgraded one level for indirectness and
      one level for suspected publication bias). Beyond eight hours postintervention,
      serum bilirubin was similar between the two groups. Duration of phototherapy was
      significantly shorter for fluid-supplemented infants, but the estimate was
      affected by heterogeneity which was not clearly explained (MD -10.70 hours, 95%
      CI -15.55 to -5.85; participants = 218; studies = 3; I2 = 67%). Fluid
      supplemented infants were less likely to require exchange transfusion (RR 0.39,
      95% CI 0.21 to 0.71; RD -0.01, 95% CI -0.04 to 0.02; participants = 462; studies
      = 6; I2 = 72%) (low quality of evidence, downgraded one level due to
      inconsistency, and another level due to suspected publication bias), and the
      estimate was similarly affected by unexplained heterogeneity. The frequencies of
      breastfeeding were similar between the fluid-supplemented and non-supplemented
      infants in days one to three based on one study (estimate on day three: MD 0.90
      feeds, 95% CI -0.40 to 2.20; participants = 60) (moderate quality of evidence,
      downgraded one level for imprecision).One study contributed to all outcome data
      in the comparison of IV versus oral fluid supplementation. In this comparison, no
      infant in either group developed abnormal neurological signs. Serum bilirubin, as
      well as the rate of change of serum bilirubin, were similar between the two
      groups at four hours after phototherapy (serum bilirubin: MD 11.00 MUmol/L (0.64
      mg/dL), 95% CI -21.58 (-1.26) to 43.58 (2.55); rate of change of serum bilirubin:
      MD 0.80 MUmol/L/hour (0.05 mg/dL/hour), 95% CI -2.55 (-0.15) to 4.15 (0.24);
      participants = 54 in both outcomes) (moderate quality of evidence for both
      outcomes, downgraded one level for indirectness). The number of infants who
      required exchange transfusion was similar between the two groups (RR 1.60, 95% CI
      0.60 to 4.27; RD 0.11, 95% CI -0.12 to 0.34; participants = 54). No infant in
      either group developed adverse effects including vomiting or abdominal
      distension. AUTHORS' CONCLUSIONS: There is no evidence that IV fluid
      supplementation affects important clinical outcomes such as bilirubin
      encephalopathy, kernicterus, or cerebral palsy in healthy, term newborn infants
      with unconjugated hyperbilirubinaemia requiring phototherapy. In this review, no
      infant developed these bilirubin-associated clinical complications. Low- to
      moderate-quality evidence shows that there are differences in total serum
      bilirubin levels between fluid-supplemented and control groups at some time
      points but not at others, the clinical significance of which is uncertain. There
      is no evidence of a difference between the effectiveness of IV and oral fluid
      supplementations in reducing serum bilirubin. Similarly, no infant developed
      adverse events or complications from fluid supplementation such as vomiting or
      abdominal distension. This suggests a need for future research to focus on
      different population groups with possibly higher baseline risks of bilirubin
      related neurological complications, such as preterm or low birthweight infants,
      infants with haemolytic hyperbilirubinaemia, as well as infants with dehydration
      for comparison of different fluid supplementation regimen.

PMID- 28762234
TI  - The link between exercise and titin passive stiffness.
AB  - NEW FINDINGS: What is the topic of this review? This review focuses on how in
      vivo and molecular measurements of cardiac passive stiffness can predict exercise
      tolerance and how exercise training can reduce cardiac passive stiffness. What
      advances does it highlight? This review highlights advances in understanding the
      relationship between molecular (titin-based) and in vivo (left ventricular)
      passive stiffness, how passive stiffness modifies exercise tolerance, and how
      exercise training may be therapeutic for cardiac diseases with increased passive
      stiffness. Exercise can help alleviate the negative effects of cardiovascular
      disease and cardiovascular co-morbidities associated with sedentary behaviour;
      this may be especially true in diseases that are associated with increased left
      ventricular passive stiffness. In this review, we discuss the inverse
      relationship between exercise tolerance and cardiac passive stiffness. Passive
      stiffness is the physical property of cardiac muscle to produce a resistive force
      when stretched, which, in vivo, is measured using the left ventricular end
      diastolic pressure-volume relationship or is estimated using echocardiography.
      The giant elastic protein titin is the major contributor to passive stiffness at
      physiological muscle (sarcomere) lengths. Passive stiffness can be modified by
      altering titin isoform size or by post-translational modifications. In both human
      and animal models, increased left ventricular passive stiffness is associated
      with reduced exercise tolerance due to impaired diastolic filling, suggesting
      that increased passive stiffness predicts reduced exercise tolerance. At the same
      time, exercise training itself may induce both short- and long-term changes in
      titin-based passive stiffness, suggesting that exercise may be a treatment for
      diseases associated with increased passive stiffness. Direct modification of
      passive stiffness to improve exercise tolerance is a potential therapeutic
      approach. Titin passive stiffness itself may be a treatment target based on the
      recent discovery of RNA binding motif 20, which modifies titin isoform size and
      passive stiffness. Translating these discoveries that link exercise and left
      ventricular passive stiffness may provide new methods to enhance exercise
      tolerance and treat patients with cardiovascular disease.

PMID- 28762236
TI  - Conceptualization, development and validation of T-QoL(c) (Teenagers' Quality of
      Life): a patient-focused measure to assess quality of life of adolescents with
      skin diseases.
AB  - BACKGROUND: Skin disease can affect the quality of life (QoL) of teenagers in a
      variety of different ways, some being unique to this age group. OBJECTIVES: To
      develop and validate a dermatology-specific QoL instrument for adolescents with
      skin diseases. METHODS: Qualitative semistructured interviews were conducted with
      adolescents with skin disease to gain in-depth understanding of how skin diseases
      affect their QoL. A prototype instrument based on the themes identified from
      content analysis of interviews was tested in several stages, using classical test
      theory and item response theory models to develop this new tool and conduct its
      psychometric evaluation. RESULTS: Thirty-three QoL issues were identified from
      semistructured interviews with 50 adolescents. A questionnaire based on items
      derived from content analysis of interviews was subjected to Rasch analysis:
      factor analysis identified three domains, therefore not supporting the validity
      of T-QoL as a unidimensional measure. Psychometric evaluation of the final 18
      item questionnaire was carried out in a cohort of 203 adolescents. Convergent
      validity was demonstrated by significant correlation with Skindex-Teen and
      Dermatology Life Quality Index (DLQI) or Children's DLQI. The T-QoL showed
      excellent internal consistency reliability: Cronbach's alpha = 0.89 for total
      scale score and 0.85, 0.60 and 0.74, respectively, for domains 1, 2 and 3. Test
      retest reliability was high in stable volunteers. T-QoL showed sensitivity to
      change in two subgroups of patients who indicated change in their self-assessed
      disease severity. CONCLUSIONS: Built on rich qualitative data from patients, the
      T-QoL is a simple and valid tool to quantify the impact of skin disease on
      adolescents' QoL; it could be used as an outcome measure in both clinical
      practice and clinical research.

PMID- 28762237
TI  - Aminoglycoside impregnated cement spacer precipitating acute kidney injury
      requiring hemodialysis.
AB  - The current standard of care for prosthetic joint infection includes two-stage
      arthroplasty, with antibiotic-impregnated cement spacers (ACS) utilized between
      the stages. We report a 75-year-old woman with previously normal renal function,
      who developed acute kidney injury (AKI) secondary to biopsy-proven acute tubular
      necrosis and acute interstitial nephritis after ACS placement containing
      tobramycin and vancomycin. Peak tobramycin level measured 25.3 mcg/mL, the
      highest value reported in the literature after ACS placement. Intermittent
      hemodialysis was initiated with subsequent full recovery of renal function. This
      paper reviews the published literature regarding the accumulation, toxicity and
      removal dynamics of aminoglycoside (AG) antibiotics and vancomycin in renal
      patients. Obtaining serum AG level should be strongly considered in patients
      experiencing AKI after ACS. Renal replacement therapy may assist in reducing
      toxic AG levels.

PMID- 28762238
TI  - Microstructure and Hardness of Buffalo's Hoofs.
AB  - The aim of this study was to describe the microstructure of hoof capsules of the
      buffalo. In addition, the study emphasized the morphometric aspects of the horn
      tubules, the Vickers nanohardness of the dorsal and abaxial walls and sole of the
      digits of the thoracic and pelvic limbs of the buffalo. The abaxial wall in the
      thoracic and pelvic digits showed larger diameter of the horn tubules when
      compared to all dorsal wall and sole. In addition, the abaxial wall of the
      thoracic digits showed larger diameter of the horn tubules when compared with the
      pelvic digits. According to the three-dimensional microtomography, the dorsal
      wall was higher in density compared with the abaxial wall. The latter exhibited
      an intermediate density, while the sole showed the lowest density. The Vickers
      nanohardness test showed that there was no difference in hardness and resistance
      between the experienced regions. However, the elastic modulus was greater on the
      transversal section of the hoof capsule. In conclusion, the results of the
      current study show that modern technologies such as microtomography and
      subsequent imaging can be used to investigate details of the basic morphology in
      different regions of the buffalo's hoof.

PMID- 28762240
TI  - Congress Chairman's Welcome Message.

PMID- 28762239
TI  - High-performance liquid chromatography-tandem mass spectrometry for simultaneous
      determination of raltegravir, dolutegravir and elvitegravir concentrations in
      human plasma and cerebrospinal fluid samples.
AB  - A simple sample treatment procedure and sensitive liquid chromatography-tandem
      mass spectrometry method were developed for the simultaneous quantification of
      the concentrations of human immunodeficiency virus-1 integrase strand transfer
      inhibitors - raltegravir, dolutegravir and elvitegravir - in human plasma and
      cerebrospinal fluid (CSF). Plasma and CSF samples (20 MUL each) were
      deproteinized with acetonitrile. Raltegravir-d3 was used as the internal
      standard. Chromatographic separation was achieved on an XBridge C18 column (50 *
      2.1 mm i.d., particle size 3.5 MUm) using acetonitrile-water (7:3, v/v)
      containing 0.1% formic acid as the mobile phase at a flow rate of 0.2 mL/min. The
      run time was 5 min. Calibration curves for all three drugs were linear in the
      range 5-1500 ng/mL for plasma and 1-200 ng/mL for CSF. The intra- and inter-day
      precision and accuracy of all three drugs in plasma were coefficient of variation
      (CV) <12.9% and 100.0 +/- 12.2%, respectively, while those in CSF were CV <12.3%
      and 100.0 +/- 7.9%, respectively. Successful validation under the same LC-MS/MS
      conditions for both plasma and CSF indicates this analytical method is useful for
      monitoring the levels of these integrase strand transfer inhibitors in the
      management of treatment of HIV-1 carriers.

PMID- 28762241
TI  - 15th Urological Association of Asia (UAA) Congress "Piecing Together Asian
      Perspectives in Urology", 4-6 Aug 2017, Hong Kong Convention and Exhibition
      Centre.

PMID- 28762242
TI  - Solvatochromism and preferential solvation of Brooker's merocyanine in water
      methanol mixtures.
AB  - The excitation energy of Brooker's merocyanine in water-methanol mixtures shows
      nonlinear behavior with respect to the mole fraction of methanol, and it was
      suggested that this behavior is related to preferential solvation by methanol. We
      investigated the origin of this behavior and its relation to preferential
      solvation using the three-dimensional reference interaction site model self
      consistent field method and time-dependent density functional theory. The
      calculated excitation energies were in good agreement with the experimental
      behavior. Analysis of the coordination numbers revealed preferential solvation by
      methanol. The free energy component analysis implied that solvent reorganization
      and solvation entropy drive the preferential solvation by methanol, while the
      direct solute-solvent interaction promotes solvation by water. The difference in
      the preferential solvation effect on the ground and excited states causes the
      nonlinear excitation energy shift. (c) 2017 Wiley Periodicals, Inc.

PMID- 28762244
TI  - An interaction energy driven biased sampling technique: A faster route to
      ionization spectra in condensed phase.
AB  - We introduce a computationally efficient approach for calculating spectroscopic
      properties, such as ionization energies (IEs) in the condensed phase. Discrete
      quantum mechanical/molecular mechanical (QM/MM) approaches for spectroscopic
      properties in a dynamic system, such as aqueous solution, need a large sample
      space to obtain converged estimates, especially for the cases where particle
      (electron) number is not conserved, such as IEs or electron affinities (EAs). We
      devise a biased sampling technique based on an approximate estimate of
      interaction energy between the solute and solvent, that accelerates the
      convergence and therefore, reduces the computational cost significantly. The
      approximate interaction energy also provides a good measure of the spectral width
      of the chromophores in the condensed phase. This technique has been tested and
      benchmarked for (i) phenol, (ii) HBDI anion (hydroxybenzylidene dimethyl
      imidazolinone), and (iii) thymine in water. (c) 2017 Wiley Periodicals, Inc.

PMID- 28762243
TI  - Quantitative susceptibility mapping: Report from the 2016 reconstruction
      challenge.
AB  - PURPOSE: The aim of the 2016 quantitative susceptibility mapping (QSM)
      reconstruction challenge was to test the ability of various QSM algorithms to
      recover the underlying susceptibility from phase data faithfully. METHODS:
      Gradient-echo images of a healthy volunteer acquired at 3T in a single
      orientation with 1.06 mm isotropic resolution. A reference susceptibility map was
      provided, which was computed using the susceptibility tensor imaging algorithm on
      data acquired at 12 head orientations. Susceptibility maps calculated from the
      single orientation data were compared against the reference susceptibility map.
      Deviations were quantified using the following metrics: root mean squared error
      (RMSE), structure similarity index (SSIM), high-frequency error norm (HFEN), and
      the error in selected white and gray matter regions. RESULTS: Twenty-seven
      submissions were evaluated. Most of the best scoring approaches estimated the
      spatial frequency content in the ill-conditioned domain of the dipole kernel
      using compressed sensing strategies. The top 10 maps in each category had similar
      error metrics but substantially different visual appearance. CONCLUSION: Because
      QSM algorithms were optimized to minimize error metrics, the resulting
      susceptibility maps suffered from over-smoothing and conspicuity loss in fine
      features such as vessels. As such, the challenge highlighted the need for better
      numerical image quality criteria. Magn Reson Med 79:1661-1673, 2018. (c) 2017
      International Society for Magnetic Resonance in Medicine.

PMID- 28762245
TI  - Electrostatics Explains the Position-Dependent Effect of G?U Wobble Base Pairs on
      the Affinity of RNA Kissing Complexes.
AB  - In the RNA realm, non-Watson-Crick base pairs are abundant and can affect both
      the RNA 3D structure and its function. Here, we investigated the formation of RNA
      kissing complexes in which the loop-loop interaction is modulated by non-Watson
      Crick pairs. Mass spectrometry, surface plasmon resonance, and UV-melting
      experiments show that the G?U wobble base pair favors kissing complex formation
      only when placed at specific positions. We tried to rationalize this effect by
      molecular modeling, including molecular mechanics Poisson-Boltzmann surface area
      (MMPBSA) thermodynamics calculations and PBSA calculations of the electrostatic
      potential surfaces. Modeling reveals that the G?U stabilization is due to a
      specific electrostatic environment defined by the base pairs of the entire loop
      loop region. The loop is not symmetric, and therefore the identity and position
      of each base pair matters. Predicting and visualizing the electrostatic
      environment created by a given sequence can help to design specific kissing
      complexes with high affinity, for potential therapeutic, nanotechnology or
      analytical applications.

PMID- 28762246
TI  - Quality indicators in the care of older persons in the emergency department: A
      systematic review of the literature.
AB  - OBJECTIVE: A systematic review of the literature was undertaken to assess the
      methodological quality of existing quality indicators (QIs) for the emergency
      department (ED) care of older persons. METHODS: MEDLINE, CINAHL, EMBASE and grey
      literature were searched. Articles were included if they addressed ED care of
      persons aged >=65 years and defined a QI amenable to influence by ED providers.
      The methodological quality of QIs was assessed using relevant items from the
      Appraisal of Indicators through Research and Evaluation and the QUALIFY tools.
      RESULTS: Sixty-one articles were included in the review, with identification of
      50 QIs meeting predefined inclusion criteria. Thirty-six of fifty ED QIs for
      older persons were process indicators. The appraisal instruments' total ratings
      ranged from 39 to 67%, with only 18 QIs scoring 50% or more for all five domains.
      CONCLUSION: There is a need for a balanced, methodologically robust set of QIs
      for care of older persons in the ED.

PMID- 28762247
TI  - Deterioration of insulin release rate response to glucose during oral glucose
      tolerance test is associated with an increased risk of incident diabetes in
      normal glucose tolerance subjects.
AB  - beta-Cell dedifferentiation, characterized by loss of glucose sensitivity (beta
      cell glucose sensitivity [betaCGS]), has been reported to play an important role
      in the development of type 2 diabetes (T2D). Traditionally, betaCGS was derived
      from C-peptide-based method. However, C-peptide was not routinely examined in
      normal subjects and diabetes never treated with insulin. Thus, the aim of the
      study was to evaluate the use of insulin in oral glucose tolerance test (OGTT) in
      estimation of beta-cell glucose response ability. A total of 1,599 subjects
      including normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and
      T2D were included in the study. A subgroup of NGT subjects (n = 591) were
      followed up for an average duration of 56.88 +/- 20.76 months. Insulin release
      rate (IRRINS ) in the function of glucose (IRRINS response to glucose [IRRG])
      during OGTT was compared with betaCGS. Both betaCGS derived from C-peptide by
      deconvolution approach and IRRG by insulin release progressively declined from
      NGT to IGT and T2D. Both betaCGS and IRRG were associated with deposit of first
      phase insulin secretion (DI1st ). After 56.88 +/- 20.76 months, 32 (5.41%) NGT
      subjects had developed T2D. NGT subjects who progressed to diabetes after follow
      up had lower IRRG and DI1st levels than those who did not (P < 0.01).
      Furthermore, multiple logistic regression analyses showed that decreased IRRG was
      a significant independent risk predictor for future diabetes after adjustment of
      age, body mass index (BMI), homeostasis model assessment (HOMA)-insulin
      resistance, DI1st and family history. NGT subjects with decreased IRRG during
      OGTT had defective early insulin secretion and were at higher risk of developing
      diabetes. IRRG could be a useful T2D predictor in NGT subjects. (c) 2017 IUBMB
      Life, 69(9):756-766, 2017.

PMID- 28762249
TI  - First Total Syntheses of Tetracenomycins C and X.
AB  - The first total syntheses of tetracenomycins C and X were achieved, featuring 1)
      preparation of a hexasubstituted naphthonitrile oxide by successive benzyne
      cycloadditions and an oxidative ring-opening reaction; 2) a novel ortho-quinone
      mono-acetal as the A-ring unit; 3) construction of three contiguous stereogenic
      centers by an asymmetric benzoin cyclization, an isoxazole oxidation, and a
      stereoselective reduction.

PMID- 28762248
TI  - Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble
      destruction gene delivery in obese Zucker rats: Proof of concept design.
AB  - Ultrasound-targeted microbubble destruction (UTMD) is a novel means of tissue
      specific gene delivery. This approach systemically infuses transgenes precoupled
      to gas-filled lipid microbubbles that are burst within the microvasculature of
      target tissues via an ultrasound signal resulting in release of DNA and
      transfection of neighboring cells within the tissue. Previous work has shown that
      adenovirus containing cDNA of UCP-1, injected into the epididymal fat pads in
      mice, induced localized fat depletion, improving glucose tolerance, and
      decreasing food intake in obese diabetic mice. Our group recently demonstrated
      that gene therapy by UTMD achieved beta cell regeneration in streptozotocin (STZ)
      treated mice and baboons. We hypothesized that gene therapy with
      BMP7/PRDM16/PPARGC1A in skeletal muscle (SKM) of obese Zucker diabetic fatty
      (fa/fa) rats using UTMD technology would produce a brown adipose tissue (BAT)
      phenotype with UCP-1 overexpression. This study was designed as a proof of
      concept (POC) project. Obese Zucker rats were administered plasmid cDNA contructs
      encoding a gene cocktail with BMP7/PRDM16/PPARGC1A incorporated within
      microbubbles and intravenously delivered into their left thigh. Controls received
      UTMD with plasmids driving a DsRed reporter gene. An ultrasound transducer was
      directed to the thigh to disrupt the microbubbles within the microcirculation.
      Blood samples were drawn at baseline, and after treatment to measure glucose,
      insulin, and free fatty acids levels. SKM was harvested for immunohistochemistry
      (IHC). Our IHC results showed a reliable pattern of effective UTMD-based gene
      delivery in enhancing SKM overexpression of the UCP-1 gene. This clearly
      indicates that our plasmid DNA construct encoding the gene combination of PRDM16,
      PPARGC1A, and BMP7 reprogrammed adult SKM tissue into brown adipose cells in
      vivo. Our pilot established POC showing that the administration of the gene
      cocktail to SKM in this rat model of genetic obesity using UTMD gene therapy,
      engineered a BAT phenotype with UCP-1 over-expression. (c) 2017 IUBMB Life,
      69(9):745-755, 2017.

PMID- 28762250
TI  - Response to Miller (2017): Communicating the role of cannabis in the risk of
      developing psychosis.

PMID- 28762251
TI  - Helicobacter pylori management in ASEAN: The Bangkok consensus report.
AB  - Helicobacter pylori (H. pylori) infection remains to be the major cause of
      important upper gastrointestinal diseases such as chronic gastritis, peptic
      ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. H.
      pylori management in ASEAN: the Bangkok consensus report gathered key opinion
      leaders for the region to review and evaluate clinical aspects of H. pylori
      infection and to develop consensus statements, rationales, and grades of
      recommendation for the management of H. pylori infection in clinical practice in
      ASEAN countries. This ASEAN Consensus consisted of 34 international experts from
      10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly
      focused on four issues: (i) epidemiology and disease association; (ii) diagnostic
      tests; (iii) management; and (iv) follow-up after eradication. The final results
      of each workshop were presented for consensus voting by all participants.
      Statements, rationale, and recommendations were developed from the available
      current evidence to help clinicians in the diagnosis and treatment of H. pylori
      and its clinical diseases.

PMID- 28762252
TI  - Enzymatic characterization of novel arylsulfatase A variants using human
      arylsulfatase A-deficient immortalized mesenchymal stromal cells.
AB  - Metachromatic leukodystrophy (MLD) is an autosomal-recessive lysosomal storage
      disease caused by mutations in the ARSA gene leading to arylsulfatase A (ARSA)
      deficiency and causing sulfatide accumulation. Main symptoms of the disease are
      progressive demyelination, neurological dysfunction, and reduced life expectancy.
      To date, more than 200 different ARSA variants have been reported in MLD
      patients. Here, we report the biochemical characterization of seven novel
      pathogenic variants (c.98T > C, c.195delC, c.229G > C, c.545C > G, c.674A > G,
      c.852T > A, and c.1274A > G), which were found when sequencing a cohort of 31
      German MLD families. For that purpose, the ARSA cDNAs carrying the respective
      mutations inserted by site-directed mutagenesis were cloned into a MigR1 (MSCV,
      IRES, GFP, retrovirus-1) vector. The constructs were overexpressed using
      retroviral gene transfer in immortalized, human multipotent mesenchymal stromal
      cells prepared from a patient deficient in ARSA activity (late infantile MLD). In
      this novel ARSA-/- cell system, the seven ARSA mutants showed ARSA activity of
      less than 10% when compared with wild type, which is evidence for the
      pathogenicity of all seven variants. In conclusion, the system of ARSA-/- 
      immortalized MSC turned out to be a helpful novel tool for the biochemical
      characterization of ARSA variants.

PMID- 28762253
TI  - Intraocular robotic interventional surgical system (IRISS): Mechanical design,
      evaluation, and master-slave manipulation.
AB  - BACKGROUND: Since the advent of robotic-assisted surgery, the value of using
      robotic systems to assist in surgical procedures has been repeatedly
      demonstrated. However, existing technologies are unable to perform complete,
      multi-step procedures from start to finish. Many intraocular surgical steps
      continue to be manually performed. METHODS: An intraocular robotic interventional
      surgical system (IRISS) capable of performing various intraocular surgical
      procedures was designed, fabricated, and evaluated. Methods were developed to
      evaluate the performance of the remote centers of motion (RCMs) using a stereo
      camera setup and to assess the accuracy and precision of positioning the tool tip
      using an optical coherence tomography (OCT) system. RESULTS: The IRISS can
      simultaneously manipulate multiple surgical instruments, change between mounted
      tools using an onboard tool-change mechanism, and visualize the otherwise
      invisible RCMs to facilitate alignment of the RCM to the surgical incision. The
      accuracy of positioning the tool tip was measured to be 0.205+/-0.003 mm. The
      IRISS was evaluated by trained surgeons in a remote surgical theatre using post
      mortem pig eyes and shown to be effective in completing many key steps in a
      variety of intraocular surgical procedures as well as being capable of performing
      an entire cataract extraction from start to finish. CONCLUSIONS: The IRISS
      represents a necessary step towards fully automated intraocular surgery and
      demonstrated accurate and precise master-slave manipulation for cataract removal
      and-through visual feedback-retinal vein cannulation.

PMID- 28762254
TI  - The Effects of Prenatal Iron Deficiency and Risperidone Treatment on the Rat
      Frontal Cortex:  A Proteomic Analysis.
AB  - Prenatal iron deficiency (pID) has been described to increase the risk for
      neurodevelopmental disorders such as autism and schizophrenia; however, the
      precise molecular mechanisms are still unknown. Here, we utilized high-throughput
      MS to examine the proteomic effects of pID in adulthood on the rat frontal cortex
      area (FCA). In addition, the FCA proteome was examined in adulthood following
      risperidone treatment in adolescence to see if these effects could be prevented.
      We identified 1501 proteins of which 100 were significantly differentially
      expressed in the FCA at postnatal day 90. Pathway analysis of proteins affected
      by pID revealed changes in metabolic processes, including the tricyclic acid
      cycle, mitochondrial dysfunction, and P13K/Akt signaling. Interestingly, most of
      these protein changes were not present in the adult pID offspring who received
      risperidone in adolescence. Considering the link between pID and several
      neurodevelopmental disorders such as autism and schizophrenia these presented
      results bring new perspectives to understand the role of iron in metabolic
      pathways and provide novel biomarkers for future studies of pID.

PMID- 28762255
TI  - Theoretical studies of spin state-specific [2 + 2] and [5 + 2] photocycloaddition
      reactions of n-(1-penten-5-yl)maleimide.
AB  - N-alkenyl maleimides are found to exhibit spin state-specific chemoselectivities
      for [2 + 2] and [5 + 2] photocycloadditions; but, reaction mechanism is still
      unclear. In this work, we have used high-level electronic structure methods (DFT,
      CASSCF, and CASPT2) to explore [2 + 2] and [5 + 2] photocycloaddition reaction
      paths of an N-alkenyl maleimide in the S1 and T1 states as well as relevant
      photophysical processes. It is found that in the S1 state [5 + 2]
      photocycloaddition reaction is barrierless and thus overwhelmingly dominant; [2 +
      2] photocycloaddition reaction is unimportant because of its large barrier. On
      the contrary, in the T1 state [2 + 2] photocycloaddition reaction is much more
      favorable than [5 + 2] photocyclo-addition reaction. Mechanistically, both S1 [5
      + 2] and T1 [2 + 2] photocycloaddition reactions occur in a stepwise,
      nonadiabatic means. In the S1 [5 + 2] reaction, the secondary C atom of the
      ethenyl moiety first attacks the N atom of the maleimide moiety forming an S1
      intermediate, which then decays to the S0 state as a result of an S1 -> S0
      internal conversion. In the T1 [2 + 2] reaction, the terminal C atom of the
      ethenyl moiety first attacks the C atom of the maleimide moiety, followed by a T1
      -> S0 intersystem crossing process to the S0 state. In the S0 state, the second
      C?C bond is formed. Our present computational results not only rationalize
      available experiments but also provide new mechanistic insights. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28762256
TI  - Morphologic and Cytochemical Characteristics of the Blood Cells of the Yellow
      Bellied Slider (Trachemys scripta scripta).
AB  - The increasing prevalence of yellow-bellied sliders (Trachemys scripta scripta)
      as pets in the European Union and also its utilization as animal models for
      experimental purposes makes crucial an accurate classification of their blood
      cells. The aim of this work was to provide a morphologic classification based on
      the cytochemical characteristics of the blood cells of 15 yellow-bellied sliders.
      Cytochemical stains included benzidine peroxidase, chloroacetate esterase, alpha
      naphthyl butyrate esterase (with and without sodium fluoride), acid phosphatase
      (with and without tartaric acid), Sudan black B, periodic acid-Schiff and
      toluidine blue. Nuclear and cellular dimensions were also measured based on quick
      Romanowsky-type stained smears. Besides erythrocytes and thrombocytes, five types
      of white blood cells were identified: heterophils, eosinophils, basophils,
      lymphocytes and monocytes. The cytochemical patterns of heterophils, eosinophils
      and basophils were unique compared to those described for other chelonians. This
      paper provides a useful guideline for clinical settings and further
      haematological studies of this species.

PMID- 28762257
TI  - Deaminative Strategy for the Visible-Light-Mediated Generation of Alkyl Radicals.
AB  - A deaminative strategy for the visible-light-mediated generation of alkyl
      radicals from redox-activated primary amine precursors is described. Abundant and
      inexpensive primary amine feedstocks, including amino acids, were converted in a
      single step into redox-active pyridinium salts and subsequently into alkyl
      radicals by reaction with an excited-state photocatalyst. The broad synthetic
      potential of this protocol was demonstrated by the alkylation of a number of
      heteroarenes under mild conditions.

PMID- 28762258
TI  - HBr-DMPU: The First Aprotic Organic Solution of Hydrogen Bromide.
AB  - HBr and DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone) form a room
      temperature-stable complex that provides a mild, effective, and selective
      hydrobrominating reagent toward alkynes, alkenes, and allenes. HBr-DMPU could
      also replace other halogenating reagents in the halo-Prins reaction, ether
      cleavage, and deoxy-bromination reactions.

PMID- 28762259
TI  - Congenital muscle dystrophy and diet consistency affect mouse skull shape
      differently.
AB  - The bones of the mammalian skull respond plastically to changes in masticatory
      function. However, the extent to which muscle function affects the growth and
      development of the skull, whose regions have different maturity patterns, remains
      unclear. Using muscle dissection and 3D landmark-based geometric morphometrics we
      investigated the effect of changes in muscle function established either before
      or after weaning, on skull shape and muscle mass in adult mice. We compared
      temporalis and masseter mass and skull shape in mice with a congenital muscle
      dystrophy (mdx) and wild type (wt) mice fed on either a hard or a soft diet. We
      found that dystrophy and diet have distinct effects on the morphology of the
      skull and the masticatory muscles. Mdx mice show a flattened neurocranium with a
      more dorsally displaced foramen magnum and an anteriorly placed mandibular
      condyle compared with wt mice. Compared with hard diet mice, soft diet mice had
      lower masseter mass and a face with more gracile features as well as labially
      inclined incisors, suggesting reduced bite strength. Thus, while the early
      maturing neurocranium and the posterior portion of the mandible are affected by
      the congenital dystrophy, the late-maturing face including the anterior part of
      the mandible responds to dietary differences irrespective of the mdx mutation.
      Our study confirms a hierarchical, tripartite organisation of the skull
      (comprising neurocranium, face and mandible) with a modular division based on
      development and function. Moreover, we provide further experimental evidence that
      masticatory loading is one of the main environmental stimuli that generate
      craniofacial variation.

PMID- 28762260
TI  - Fuzziness enables context dependence of protein interactions.
AB  - Proteins may undergo adaptive structural transitions to accommodate to their
      cellular milieu and respond to external signals. Modulation of conformational
      ensembles can rewire the intra- or intermolecular interaction networks and shift
      between different functional states. Adaptive conformational transitions are
      associated with protein fuzziness, which enables (a) rewiring interaction
      networks via alternative motifs, (b) new functional features via allosteric
      motifs, (c) functional switches upon post-translational modifications, or (d)
      regulation of higher-order organizations. We propose that all these context
      dependent functional changes are intertwined with structural multiplicity or
      dynamic disorder in protein assemblies and can only be described by stochastic
      structure-function relationships.

PMID- 28762261
TI  - Self-Templating Construction of Hollow Amorphous CoMoS4 Nanotube Array towards
      Efficient Hydrogen Evolution Electrocatalysis at Neutral pH.
AB  - Environmentally friendly electrochemical hydrogen production needs the
      development of earth-abundant catalyst materials for the hydrogen evolution
      reaction with high activity and durability at neutral pH. In this work, the self
      templating construction of a hollow amorphous CoMoS4 nanotube array on carbon
      cloth (CoMoS4 NTA/CC) is reported, using hydrothermal treatment of a Co(OH)F
      nanowire array on CC in (NH4 )2 MoS4 solution. When used as a 3D electrode for
      hydrogen evolution electrocatalysis, the resulting CoMoS4 NTA/CC demonstrates
      superior catalytic activity and strong long-term electrochemical durability in
      1.0 M phosphate buffer solution (pH=7). It shows small onset overpotential of 21
      mV and requires low overpotentials of 104 and 179 mV to drive geometrical current
      densities of 10 and 50 mA cm-2 , respectively. Density functional theory
      calculations suggest that CoMoS4 has a more favorable hydrogen adsorption free
      energy than Co(OH)F.

PMID- 28762262
TI  - Embodiment Mediates the Relationship between Avoidant Attachment and Eating
      Disorder Psychopathology.
AB  - OBJECTIVE: The overvaluation of body shape and weight of persons with eating
      disorders (EDs) is putatively explained by a disturbance in the way they
      experience their own body (embodiment). Moreover, attachment disorders seem to
      promote the use of body as source for self-definition. Therefore, we assessed the
      role of embodiment in the connection between attachment styles and ED
      psychopathology. METHOD: One-hundred and thirteen ED patients and 117 healthy
      subjects completed the Identity and Eating Disorders (IDEA) Questionnaire, the
      Eating Disorder Inventory-2 (EDI-2) and the Experiences in Close Relationships
      Scale. RESULTS: Eating disorder patients displayed IDEA, EDI-2 and Experiences in
      Close Relationships scores significantly higher than controls. IDEA total and
      subtotal scores mediated entirely the influence of avoidant attachment on EDI-2
      interoceptive awareness and impulsivity. DISCUSSION: These findings demonstrate a
      relationship between insecure attachment and disorders of identity and embodiment
      and point to embodiment as a possible mediator between avoidant attachment and
      specific ED psychopathological traits. Copyright (c) 2017 John Wiley & Sons, Ltd
      and Eating Disorders Association.

PMID- 28762264
TI  - Chemically Edited Exosomes with Dual Ligand Purified by Microfluidic Device for
      Active Targeted Drug Delivery to Tumor Cells.
AB  - Exosomes, which are lipid membrane-bound nanovesicles (50-150 nm in diameter),
      have aroused extensive attention for their potential applications in invasive
      molecular and stand for a new therapeutic delivery system. However, they are
      limited by poor targeting ability and a lack of efficient isolation techniques.
      Here, we present a three-dimensional nanostructured microfluidic chip, in which
      arrays of micropillars were functionalized with crisscrossed multiwall carbon
      nanotubes by chemical deposition, to capture exosomes with high efficiency
      through a combination of a specific recognition molecule (CD63) and the unique
      topography of the nanomaterials. As is proven, this nanostructured interface
      substantially made the immuno capturing of exosomes more efficient. A high
      percentage of intact vesicles <150 nm were readily purified. As a further
      application, we added functionality to the exosomes by a chemical editing
      approach for targeted drug delivery. Donor cells were labeled chemically with
      dual ligands (biotin and avidin) in the phospholipid membrane and encapsulated
      drugs in the cytosol. Though the engineered donor cells secreted exosomes, the
      dual ligands, together with the drugs, were inherited by the exosomes, which were
      then isolated with the microfluidic chip. Then, the isolated exosomes were used
      as drug delivery vehicles and showed strong targeting abilities to tumor cells
      and highly efficient receptor-mediated cellular uptake when exposed to recipient
      cells. Thus, the anticancer effect of chemotherapeutic drugs was improved
      significantly. It suggested that this platform could provide a useful tool for
      isolating intact exosomes with high efficiency and exploiting their natural
      carrier function to deliver chemotherapeutic drugs to tumor cells with increased
      efficacy and targeting capacity.

PMID- 28762263
TI  - Lipid Association of India Expert Consensus Statement on Management of
      Dyslipidemia in Indians 2016: Part 1.

PMID- 28762265
TI  - Fabrication of Heterogeneous-Phase Solid-Solution Promoting Band Structure and
      Charge Separation for Enhancing Photocatalytic CO2 Reduction: A Case of ZnXCa1
      XIn2S4.
AB  - Photocatalytic CO2 reduction into solar fuels illustrates huge charm for
      simultaneously settling energy and environmental issues. The photoreduction
      ability of a semiconductor is closely correlated to its conduction band (CB)
      position. A homogeneous-phase solid-solution with the same crystal system always
      has a monotonously changed CB position, and the high CB level has to be
      sacrificed to achieve a benign photoabsorption. Herein, we report the fabrication
      of heterogeneous-phase solid-solution ZnXCa1-XIn2S4 between trigonal ZnIn2S4 and
      cubic CaIn2S4. The ZnXCa1-XIn2S4 solid solutions with orderly tuned
      photoresponsive range from 540 to 640 nm present a more negative CB level and
      highly enhanced charge-separation efficiency. Profiting from these merits, all of
      these ZnXCa1-XIn2S4 solid solutions exhibit remarkably strengthened
      photocatalytic CO2 reduction performance under visible light (lambda > 420 nm)
      irradiation. Zn0.4Ca0.6In2S4, bearing the most negative CB position and highest
      charge-separation efficiency, casts the optimal photocatalytic CH4 and CO
      evolution rates, which reach 16.7 and 6.8 times higher than that of ZnIn2S4 and
      7.2 and 3.9 times higher than that of CaIn2S4, respectively. To verify the
      crucial role of the heterogeneous-phase solid solution in promoting the band
      structure and photocatalytic performance, another heterogeneous-phase solid
      solution ZnXCd1-XIn2S4 has been synthesized. It also displays an upshifted CB
      level and promoted charge separation. This work may provide a new perspective
      into the development of an efficient visible-light driven photocatalyst for CO2
      reduction and other photoreduction reactions.

PMID- 28762266
TI  - Gradated Mixed Hole Transport Layer in a Perovskite Solar Cell: Improving
      Moisture Stability and Efficiency.
AB  - We demonstrate a simple and facile way to improve the efficiency and moisture
      stability of perovskite solar cells using commercially available hole transport
      materials, 2,2',7,7'-tetrakis-(N,N-di-4-methoxyphenylamino)-9,9'-spirobifluorene
      (spiro-OMeTAD) and poly(3-hexylthiophene) (P3HT). The hole transport layer (HTL)
      composed of mixed spiro-OMeTAD and P3HT exhibited favorable vertical phase
      separation. The hydrophobic P3HT was more distributed near the surface (the air
      atmosphere), whereas the hydrophilic spiro-OMeTAD was more distributed near the
      perovskite layer. This vertical separation resulted in improved moisture
      stability by effectively blocking moisture in air. In addition, the optimized
      composition of spiro-OMeTAD and P3HT improved the efficiency of the solar cells
      by enabling fast intramolecular charge transport. In addition, a suitable energy
      level alignment facilitated charge transfer. A device fabricated using the mixed
      HTL exhibited enhanced performance, demonstrating 18.9% power conversion
      efficiency and improved moisture stability.

PMID- 28762267
TI  - Charge-Reversible Multifunctional HPMA Copolymers for Mitochondrial Targeting.
AB  - Mitochondrial-oriented delivery of anticancer drugs has been considered as a
      promising strategy to improve the antitumor efficiency of chemotherapeutics.
      However, the physiological and biological barriers from the injection site to the
      final mitochondrial action site remain great challenges. Herein, a novel
      mitochondrial-targeted multifunctional nanocomplex based on N-(2-hydroxypropyl)
      methacrylamide (HPMA) copolymers (MPC) is designed to enhance drug accumulation
      in mitochondria. MPC possesses various functions such as extracellular pH
      response, superior cellular uptake, lysosomal escape, and mitochondrial
      targeting. In detail, MPC was formed by two oppositely charged HPMA copolymers,
      that is, positively charged mitochondrial-targeting guanidine group-modified
      copolymers and charge-reversible 2,3-dimethylmaleic anhydride (DMA)-modified
      copolymers (P-DMA). It was validated that MPC could remain stable in the blood
      circulation (pH 7.4) but could be cleaved to expose the positive charge of the
      guanidine group immediately in response to the mild acidity of tumor tissues (pH
      6.5). The gradual exposure of positively charged guanidine will simultaneously
      facilitate endocytosis, endosomal/lysosomal escape, and mitochondrial targeting.
      The in vitro experiments showed that compared with copolymers without guanidine
      modification, the cellular uptake and mitochondrial-targeting ability of MPC in
      the simulated tumor environment (MPC@pH6.5) separately increased 4.3- and 23.8
      fold, respectively. The in vivo experiments were processed on B16F10 tumor
      bearing C57 mice, and MPC showed the highest accumulation in the tumor site and a
      peak tumor inhibition rate of 82.9%. In conclusion, multifunctional mitochondrial
      targeting HPMA copolymers provide a novel and versatile approach for cancer
      therapy.

PMID- 28762268
TI  - Direct Covalent Coupling of Porphyrins to Graphene.
AB  - Graphene-porphyrin nanohybrid materials with a direct covalent linkage between
      the graphene carbon network and the functional porphyrin unit have been
      successfully synthesized via a one-pot reductive diazotation approach. A graphite
      potassium intercalation compound (KC8) was dispersed in THF, and different
      isolated porphyrin-diazonium salts were added. The direct covalent binding and
      the detailed characterization of the functional hybrid material were carried out
      by Raman spectroscopy, TG-MS, UV/vis, and fluorescence spectroscopy. LDI-ToF mass
      spectrometry was introduced as a new versatile and sensitive tool to investigate
      covalently functionalized graphene derivatives and to establish the composition
      of the respective nanohybrid materials.

PMID- 28762269
TI  - Intrinsically Stretchable Nanostructured Silver Electrodes for Realizing
      Efficient Strain Sensors and Stretchable Organic Photovoltaics.
AB  - In this study, a new hybrid electrode featuring a high gauge factor of >30,
      decent stretchability (100% of the original conductivity can be retained after 50
      cycles of stretching under a 20% strain without prestrain treatment), high
      transmittance (>70%) across 400-900 nm, and a good sheet resistance (<50 Omega sq
      1) was successfully exploited. These superior properties were revealed to
      originate from the reversible phase separation endowed by the nanogranular-like
      morphology formed in Ag. Owing to such discrete nanomorphology, the free volume
      within this Ag electrode is susceptible to the applied tensile strain and the
      ensuing change in conductivity enables the realization of an efficient strain
      sensor. Besides, a representative PTB7-th:PC71BM organic photovoltaic (OPV) using
      this electrode (with the assistance of a wrinkled scaffold to reinforce the
      stretchability of the active layer) can exhibit a power-conversion efficiency
      (PCE) of 6% along with high deformability, for which 75% of its original PCE is
      retained after 50 cycles of stretching under a 20% strain. Meanwhile, a
      representative all-polymer OPV consisting of a PTB7-th:N2200 blend, in which the
      N2200 has a better mechanical stretchability than that of PC71BM, can maintain
      over 96% of its original PCE after 50 cycles of stretching (under a 20% strain)
      without employing the wrinkled scaffold. Such promising performance in
      stretchable OPVs is among the state-of-the-art results reported to date.

PMID- 28762270
TI  - Catalytic Asymmetric Synthesis and Stereochemical Revision of (+)-Cryptoconcatone
      H.
AB  - The total synthesis and structural revision of (+)-cryptoconcatone H are
      described. Guided by computational studies for the final structure assignment,
      the stereogenic centers at the tetrahydropyran moiety of (+)-cryptoconcatone H
      were assembled through catalytic asymmetric methodologies: Krische allylation,
      cross-metathesis reaction, and THP formation via Pd(II)-catalyzed cyclization.
      Finally, a Krische allylation reaction established the last stereocenter, and the
      lactone moiety was formed by ring-closing metathesis.

PMID- 28762271
TI  - Highly Hydrophilic, Two-photon Fluorescent Terpyridine Derivatives Containing
      Quaternary Ammonium for Specific Recognizing Ribosome RNA in Living Cells.
AB  - A two-photon fluorescent probe (J1) that selectively stains intracellular
      nucleolar RNA was screened from three water-soluble terpyridine derivatives (J1
      J3) with quaternary ammonium groups. The photophysical properties of J1-J3 were
      systemically investigated both experimentally and theoretically, revealing that
      J1-J3 possess large Stokes shifts and the two-photon absorption action cross
      sections range from 38 to 97 GM in the near-infrared region. This indicates that
      J1 could specifically stain nucleoli by targeting the nucleolar rRNA from the
      recognition experiments in vitro, the two-photon imaging experiments, and the
      stimulated emission depletion in vivo. The mechanism of action in which J1 binds
      to the nucleolar rRNA was researched via both experiments and molecular modeling.
      The high binding selectivity of J1 to nucleolar RNA over cytosolic RNA made this
      probe a potential candidate to visualize rRNA probe in the living cells.

PMID- 28762272
TI  - Atomically Thin Interfacial Suboxide Key to Hydrogen Storage Performance
      Enhancements of Magnesium Nanoparticles Encapsulated in Reduced Graphene Oxide.
AB  - As a model system for hydrogen storage, magnesium hydride exhibits high hydrogen
      storage density, yet its practical usage is hindered by necessarily high
      temperatures and slow kinetics for hydrogenation-dehydrogenation cycling.
      Decreasing particle size has been proposed to simultaneously improve the kinetics
      and decrease the sorption enthalpies. However, the associated increase in surface
      reactivity due to increased active surface area makes the material more
      susceptible to surface oxidation or other side reactions, which would hinder the
      overall hydrogenation-dehydrogenation process and diminish the capacity. Previous
      work has shown that the chemical stability of Mg nanoparticles can be greatly
      enhanced by using reduced graphene oxide as a protecting agent. Although no
      bulklike crystalline MgO layer has been clearly identified in this graphene
      encapsulated/Mg nanocomposite, we propose that an atomically thin layer of
      honeycomb suboxide exists, based on first-principles interpretation of Mg K-edge
      X-ray absorption spectra. Density functional theory calculations reveal that in
      contrast to conventional expectations for thick oxides this interfacial oxidation
      layer permits H2 dissociation to the same degree as pristine Mg metal with the
      added benefit of enhancing the binding between reduced graphene oxide and the Mg
      nanoparticle, contributing to improved mechanical and chemical stability of the
      functioning nanocomposite.

PMID- 28762273
TI  - Systematic Analysis of Lysine Acetylation in the Halophilic Archaeon Haloferax
      mediterranei.
AB  - Lysine acetylation is a reversible and highly regulated post-translational
      modification that plays a critical role in regulating many aspects of cellular
      processes, both in bacteria and in eukaryotes. However, this modification has not
      been systematically studied in archaea. Herein, we report the lysine acetylome of
      a model haloarchaeon, Haloferax mediterranei. Using immunoaffinity enrichment and
      LC-MS/MS analysis, we identified 1017 acetylation sites in 643 proteins,
      accounting for 17.3% of the total proteins in this haloarchaeon. Bioinformatics
      analysis indicated that lysine acetylation mainly distributes in cytoplasm (94%)
      and participates in protein biosynthesis and carbon metabolism. Specifically, the
      acetylation of key enzymes in PHBV biosynthesis further suggested that
      acetylation plays a key role in the energy and carbon storage. In addition, a
      survey of the acetylome revealed a universal rule in acetylated motifs: a
      positively charged residue (K, R, or H) located downstream of acetylated lysine
      at the positions +1, +2, or +3. Interestingly, we identified acetylation in
      several replication initiation proteins Cdc6; mutation on the acetylated site of
      Cdc6A destroyed the Autonomous Replication Sequence (ARS) activity of its
      adjacent origin oriC1. Our study indicates that lysine acetylation is an abundant
      modification in H. mediterranei, and plays key roles in the processes of
      replication, protein biosynthesis, central metabolism, and carbon storage. This
      acetylome of H. mediterranei provides opportunities to explore the physiological
      role of acetylation in halophilic archaea.

PMID- 28762274
TI  - Efficient Carrier Multiplication in Colloidal Silicon Nanorods.
AB  - Auger recombination lifetimes, absorption cross sections, and the quantum yields
      of carrier multiplication (CM), or multiexciton generation (MEG), were determined
      for solvent-dispersed silicon (Si) nanorods using transient absorption
      spectroscopy (TAS). Nanorods with an average diameter of 7.5 nm and aspect ratios
      of 6.1, 19.3, and 33.2 were examined. Colloidal Si nanocrystals of similar
      diameters were also studied for comparison. The nanocrystals and nanorods were
      passivated with organic ligands by hydrosilylation to prevent surface oxidation
      and limit the effects of surface trapping of photoexcited carriers. All samples
      used in the study exhibited relatively efficient photoluminescence. The Auger
      lifetimes increased with nanorod length, and the nanorods exhibited higher CM
      quantum yield and efficiency than the nanocrystals with a similar band gap energy
      Eg. Beyond a critical length, the CM quantum yield decreases. Nanorods with the
      aspect ratio of 19.3 had the highest CM quantum yield of 1.6 +/- 0.2 at 2.9Eg,
      which corresponded to a multiexciton yield that was twice as high as observed for
      the spherical nanocrystals.

PMID- 28762276
TI  - Synthesis of Aryl C-Glycosides via Iron-Catalyzed Cross Coupling of Halosugars:
      Stereoselective Anomeric Arylation of Glycosyl Radicals.
AB  - We have developed a novel diastereoselective iron-catalyzed cross-coupling
      reaction of various glycosyl halides with aryl metal reagents for the efficient
      synthesis of aryl C-glycosides, which are of significant pharmaceutical interest
      due to their biological activities and resistance toward metabolic degradation. A
      variety of aryl, heteroaryl, and vinyl metal reagents can be cross-coupled with
      glycosyl halides in high yields in the presence of a well-defined iron complex,
      composed of iron(II) chloride and a bulky bisphosphine ligand, TMS-SciOPP. The
      chemoselective nature of the reaction allows the use of synthetically versatile
      acetyl-protected glycosyl donors and the incorporation of various functional
      groups on the aryl moieties, producing a diverse array of aryl C-glycosides,
      including Canagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2),
      and a prevailing diabetes drug. The cross-coupling reaction proceeds via
      generation and stereoselective trapping of glycosyl radical intermediates,
      representing a rare example of highly stereoselective carbon-carbon bond
      formation based on iron catalysis. Radical probe experiments using 3,4,6-tri-O
      acetyl-2-O-allyl-alpha-d-glucopyranosyl bromide (8) and 6-bromo-1-hexene (10)
      confirm the generation and intermediacy of the corresponding glycosyl radicals.
      Density functional theory (DFT) calculations reveal that the observed anomeric
      diastereoselectivity is attributable to the relative stability of the conformers
      of glycosyl radical intermediates. The present cross-coupling reaction
      demonstrates the potential of iron-catalyzed stereo- and chemoselective carbon
      carbon bond formation in the synthesis of bioactive compounds of certain
      structural complexity.

PMID- 28762275
TI  - Ribosome Rescue Inhibitors Kill Actively Growing and Nonreplicating Persister
      Mycobacterium tuberculosis Cells.
AB  - The emergence of Mycobacterium tuberculosis (MTB) strains that are resistant to
      most or all available antibiotics has created a severe problem for treating
      tuberculosis and has spurred a quest for new antibiotic targets. Here, we
      demonstrate that trans-translation is essential for growth of MTB and is a viable
      target for development of antituberculosis drugs. We also show that an inhibitor
      of trans-translation, KKL-35, is bactericidal against MTB under both aerobic and
      anoxic conditions. Biochemical experiments show that this compound targets helix
      89 of the 23S rRNA. In silico molecular docking predicts a binding pocket for KKL
      35 adjacent to the peptidyl-transfer center in a region not targeted by
      conventional antibiotics. Computational solvent mapping suggests that this pocket
      is a druggable hot spot for small molecule binding. Collectively, our findings
      reveal a new target for antituberculosis drug development and provide critical
      insight on the mechanism of antibacterial action for KKL-35 and related 1,3,4
      oxadiazole benzamides.

PMID- 28762277
TI  - A case of early-onset familial Alzheimer's disease with both APP and novel PSEN2
      mutations presenting with non-amnestic features.

PMID- 28762278
TI  - Co-ingested alcohol and the timing of deliberate self-poisonings.
AB  - OBJECTIVE: Investigating diurnal variation in the timing of suicidal behaviours
      offers opportunity to better understand its various proximal risk factors. Acute
      use of alcohol is a potent proximal risk factor for suicidal behaviour, though
      the nature of this risk is poorly understood. The aim of this study was to
      compare the diurnal variation in time of poison ingestion between deliberate self
      poisonings that involve alcohol versus those that do not. METHODS: A
      retrospective analysis of consecutive presentations to a toxicology service
      following deliberate self-poisoning, 1996-2016. An independent samples Kolmogorov
      Smirnov test was performed to test the null hypothesis that the diurnal
      distribution of poison ingestion time was equal across self-poisonings that did
      and did not involve alcohol co-ingestion. Presence of circadian rhythmicity was
      established using cosinor analysis. RESULTS: A total of 11,088 deliberate self
      poisoning records, for 7467 patients (60.8% females), were included in the
      analysis. In all, 31.3% of the total records involved alcohol co-ingestion.
      Distribution of exposure time was significantly different between deliberate self
      poisonings that did and did not involve alcohol ( p < 0.001). The alcohol co
      ingestion group showed a significantly greater prominent peak with poisoning
      occurring later in the evening (~20:00 hours) compared to poisonings that did not
      involve alcohol (~18:00 hours). CONCLUSION: This study exposed the differential
      diurnal patterns in deliberate self-poisoning according to the presence of
      alcohol co-ingestion. This analysis adds to the accumulating evidence that
      suicidal behaviour that involves alcohol co-ingestion represents a distinct
      subtype, which may be driven by alcohol consumption patterns in society. This
      also means that this large proportion of deliberate self-poisonings may not
      otherwise have occurred if it were not for alcohol consumption, underscoring the
      importance of drug and alcohol services for alcohol-related self-harm.

PMID- 28762279
TI  - Family factors in adolescent problematic Internet gaming: A systematic review.
AB  - Background and aims Familial influences are known to affect the likelihood of an
      adolescent becoming a problem gamer. This systematic review examined some of the
      key findings in empirical research on family factors related to adolescent
      problem gaming. Methods A total of 14 studies in the past decade were evaluated.
      Family-related variables included: (a) parent status (e.g., socioeconomic status
      and mental health), (b) parent-child relationship (e.g., warmth, conflict, and
      abuse), (c) parental influence on gaming (e.g., supervision of gaming, modeling,
      and attitudes toward gaming), and (d) family environment (e.g., household
      composition). Results The majority of studies have focused on parent-child
      relationships, reporting that poorer quality relationships are associated with
      increased severity of problem gaming. The paternal relationship may be protective
      against problem gaming; therefore, prevention programs should leverage the
      support of cooperative fathers. Discussion The intergenerational effects of
      problem gaming require further attention, in light of adult gamers raising their
      children in a gaming-centric environment. Research has been limited by a reliance
      on adolescent self-report to understand family dynamics, without gathering
      corroborating information from parents and other family members. The very high
      rates of problem gaming (>10%) reported in general population samples raise
      concerns about the validity of current screening tools. Conclusions Interventions
      for adolescents may be more effective in some cases if they can address familial
      influences on problem gaming with the active co-participation of parents, rather
      than enrolling vulnerable adolescents in individual-based training or temporarily
      isolating adolescents from the family system.

PMID- 28762280
TI  - Anorexia nervosa: Eating disorder or body image disorder?

PMID- 28762281
TI  - Clinical significance of farnesoid X receptor expression in thyroid neoplasia.
AB  - AIM: To evaluate the clinical significance of farnesoid X receptor (FXR) in
      thyroid neoplasia. PATIENTS & METHODS: FXR expression was assessed
      immunohistochemically on 88 thyroid neoplastic tissues (benign = 44, malignant =
      44). RESULTS: Enhanced FXR was more frequently observed in papillary carcinomas
      compared with hyperplastic nodules (p = 0.0489). In malignant lesions, elevated
      FXR was associated with capsular (p = 0.0004) and vascular invasion (p = 0.0056)
      and increased follicular cells' proliferative rate (p < 0.0001). Elevated FXR
      expression was also associated with larger tumor size (p = 0.0086), presence of
      lymph node metastases (p = 0.0239) and lymphatic invasion (p = 0.0086) and
      increased recurrence rate risk (p = 0.0239). CONCLUSION: FXR may be associated
      with tumor aggressiveness that affects patients' survival in thyroid neoplasia.

PMID- 28762282
TI  - Ketamine: miracle drug or latest fad?

PMID- 28762283
TI  - The risk of biochemical recurrence for intermediate-risk prostate cancer after
      radical prostatectomy.
AB  - OBJECTIVES: To report oncological outcomes including biochemical recurrence (BR)
      following radical prostatectomy (RP) from a large consecutive cohort operated in
      an 18-year period. Additionally, an in-depth analysis of outcomes among D'Amico
      intermediate-risk patients is presented. MATERIALS AND METHODS: A total of 2,091
      patients with PCa who underwent RP at Department of Urology, Rigshospitalet,
      Copenhagen, Denmark between 1995 and 2013 were included. Univariate and multiple
      cause-specific Cox regression analyses for BR were applied using competing risk
      models. Death prior to BR was considered a competing event. BR was defined as the
      first PSA >=0.2 ng/ml. No patient received adjuvant therapy prior to BR. RESULTS:
      Overall, the 5- and 10-years cumulative incidence of BR was 21.9% and 32.0%. The
      10-year cumulative incidence of BR was 17.9%, 31.9% and 47.9% for D'Amico low-,
      intermediate- and high-risk patients, respectively. Among intermediate-risk
      patients, the 10-year cumulative incidence of BR was 24.0%, 39.9%, and 47.9% for
      patients harboring one, two or three risk factors, respectively (Gray test: p <
      0.0001). In multivariate analysis, PSA, RP GS, pT category, and positive surgical
      margins were significantly associated with an increased risk of BR. CONCLUSIONS:
      The risk of BR among patients with intermediate-risk disease is not uniform and
      is highly dependent on the number of risk factors per patient. Intermediate-risk
      patients have a comparable risk of recurrence as high-risk patients, and this
      should be taken into consideration when counseling patients prior to RP.

PMID- 28762284
TI  - Systematic mapping study of data mining-based empirical studies in cardiology.
AB  - Data mining provides the methodology and technology to transform huge amount of
      data into useful information for decision making. It is a powerful process to
      extract knowledge and discover new patterns embedded in large data sets. Data
      mining has been increasingly used in medicine, particularly in cardiology. In
      fact, data mining applications can greatly benefits all parts involved in
      cardiology such as patients, cardiologists and nurses. This article aims to
      perform a systematic mapping study so as to analyze and synthesize empirical
      studies on the application of data mining techniques in cardiology. A total of
      142 articles published between 2000 and 2015 were therefore selected, studied and
      analyzed according to the four following criteria: year and channel of
      publication, research type, medical task and empirical type. The results of this
      mapping study are discussed and a list of recommendations for researchers and
      cardiologists is provided.

PMID- 28762285
TI  - Problematic medical marijuana, but not all cannabinoids?

PMID- 28762286
TI  - Childhood-Onset Epileptic Encephalopathy Associated With Isolated Focal Cortical
      Dysplasia and a Novel TSC1 Germline Mutation.
AB  - Tuberous sclerosis complex (TSC) is an autosomal-dominant inheritable
      neurocutaneous disease due to mutations within the TSC1 and TSC2 genes. Many
      patients present with West syndrome, a severe epilepsy syndrome characterized by
      the triad of infantile spasms, an interictal electroencephalogram (EEG) pattern
      termed hypsarrhythmia (continuous slow activity with an amplitude higher than 300
      uV and multiregional spikes/polyspikes/sharp waves) and developmental regression.
      In this study, we report on a previously healthy patient with positive family
      history of epilepsy with new-onset epileptic encephalopathy at the age of 9
      years. Clinical signs alone were not sufficient to establish the diagnosis of TSC
      but epilepsy panel screening revealed a novel frameshift mutation (c.90delA;
      p.Glu31Argfs*12) within the TSC1 gene. Segregation gene analysis detected the
      same mutation in the mother. Cranial magnetic resonance imaging (MRI) studies
      from the index patient and his mother revealed a similar pattern of isolated
      subcortical white matter lesions resembling most likely focal cortical dysplasia
      (FCD) type IIb. In summary, in these 2 related patients, a novel TSC1 frameshift
      mutation was associated with an isolated FCD type IIb in the absence of further
      CNS abnormalities usually encountered in patients with TSC, fostering our
      understanding of the broad mutation spectra in the TSC1 gene and the close
      relationship between cortical tubers and FCD type IIb.

PMID- 28762287
TI  - Disease Resistance to Multiple Fungal and Oomycete Pathogens Evaluated Using a
      Recombinant Inbred Line Population in Pepper.
AB  - Incorporating disease resistance into cultivars is a primary focus of modern
      breeding programs. Resistance to pathogens is often introgressed from landrace or
      wild individuals with poor fruit quality into commercial-quality cultivars. Sites
      of multiple disease resistance (MDR) are regions or "hot spots" of the genome
      with closely linked genes for resistance to different pathogens that could enable
      rapid incorporation of resistance. An F2-derived F6 recombinant inbred line
      population from a cross between 'Criollo de Morelos 334' (CMM334) and 'Early
      Jalapeno' was evaluated in inoculated fruit studies for susceptibility to
      oomycete and fungal pathogens: Phytophthora capsici, P. nicotianae, Botrytis
      cinerea, Fusarium oxysporum, F. solani, Sclerotinia sclerotiorum, Alternaria
      spp., Rhizopus oryzae, R. stolonifer, and Colletotrichum acutatum. All isolates
      evaluated were virulent on pepper. Significant differences in disease
      susceptibility were identified among lines for each of the pathogens evaluated.
      P. capsici was the most virulent pathogen, while R. oryzae and one Sclerotinia
      isolate were the least virulent. Quantitative trait loci associated with
      resistance were identified for Alternaria spp. and S. sclerotiorum. Positive
      correlations in disease incidence were detected between Alternaria spp. and F.
      oxysporum, F. solani, and C. acutatum, as well as between C. acutatum and
      Botrytis spp., F. oxysporum, F. solani, and P. capsici. No sites of MDR were
      identified for pathogens tested; however, positive correlations in disease
      incidence were detected among pathogens suggesting there may be genetic linkage
      among resistance genes in CM334 and Early Jalapeno.

PMID- 28762288
TI  - The phytological future of prostate cancer staging: PSMA-PET and the dandelion
      theory.
AB  - PSMA-PET is changing how we stage prostate cancer, both in the primary setting
      and with relapse after treatment. It allows us to identify lesions in the bones
      and lymph nodes that were not previously visible on conventional imaging with
      bone scan and CT/MRI. In this Special Report we review the 'state of the art' for
      PSMA imaging and discuss the implications for treatment decisions in prostate
      cancer. We liken early high risk or metastatic prostate to a common phytological
      problem: the dandelion. In this analogous situation, we consider the additional
      evidence needed for us to start plucking out the original dandelion and for us to
      focus attention on killing the seeded weeds that are identifiable elsewhere in
      the lawn.

PMID- 28762289
TI  - There Is No Performance, There Is Just This Moment: The Role of Mindfulness
      Instruction in Promoting Health and Well-Being Among Students at a Highly-Ranked
      University in the United States.
AB  - Mindfulness-based stress reduction (MBSR) has been shown to improve health
      outcomes across populations. We explored the feasibility, acceptability, and
      initial effects of a pilot MBSR program at a highly-ranked university in the
      United States. We conducted 23 in-depth interviews with 13 students. Interviews
      explored stressors and coping mechanisms, experiences with MBSR, and its reported
      impact and potential future use. Interviews were analyzed using thematic content
      and narrative analyses. Results indicated that students are exposed to a very
      high level of constant stress related to the sheer amount of work and activities
      that they have and the pervasive surrounding university culture of perfectionism.
      MBSR offered an opportunity to step back and gain perspective on issues of
      balance and priorities and provided concrete techniques to counter the effects of
      stressors. We conclude that MBSR and mindfulness programs may contribute to more
      supportive university learning environments and greater health and well-being
      among students.

PMID- 28762290
TI  - Implications of Synkinesis in Unilateral Vocal Fold Paralysis.
AB  - Objectives In patients with unilateral vocal fold paralysis (UVFP), laryngeal
      electromyography (LEMG) occasionally observes synkinesis in laryngeal muscles, a
      condition that could impair vocal fold mobility and voice control. This study
      aims to evaluate the impact of synkinesis on UVFP patients. Study Design A
      retrospective case-control study. Setting Medical center. Subjects and Methods
      Patients with UVFP onset >6 months were recruited (N = 104). The outcome
      measurements included LEMG, quantitative LEMG analysis of thyroarytenoid-lateral
      cricoarytenoid (TA-LCA) muscle complex, glottal gap measured by
      videolaryngostroboscopy, voice-related quality of life, and voice acoustic
      analysis. Results According to the LEMG analysis, 8 patients (8%) had synkinesis,
      and 96 (92%) did not. In the synkinesis group, TA-LCA turn frequency in the
      lesioned side was comparable to that in the healthy side ( P = .52). Patients in
      the synkinesis group had higher TA-LCA turn frequency ( P = .001), higher
      probability of cricothyroid muscle dysfunction ( P = .04), and better voice
      related quality of life ( P = .01) but objective voice outcomes comparable to
      those in the nonsynkinesis group. Conclusions Patients with synkinesis will have
      near-complete restoration in TA-LCA turn frequency but still experience voice
      impairment, a finding that is compatible with the mechanism of aberrant
      reinnervation. However, patients with synkinesis have better disease-related
      quality of life than do those without synkinesis.

PMID- 28762292
TI  - Tonsillectomy in Children with Down Syndrome: A National Cohort of Inpatients.
AB  - Objective To describe the cost, length of stay, and incidence of postoperative
      hemorrhage associated with Down syndrome (DS) patients undergoing tonsillectomy
      in a national sample of inpatient children. Study Design This study uses a
      national cross-sectional cohort to analyze children with and without DS
      undergoing tonsillectomy with or without adenoidectomy. Setting 2012 Healthcare
      Cost and Utilization Project Kids' Inpatient Database. Subjects and Methods The
      database was analyzed for postoperative hemorrhage and respiratory compromise,
      length of stay, and total charges of hospital stay. These outcomes were compared
      between patients with DS vs patients without DS. Results In total, 7512 patients
      were identified who underwent tonsillectomy: 7159 patients without DS and 353
      patients with DS. The non-DS group was younger with a median age of 3 years
      (range, 0-18) compared with a DS median age of 4 years (range, 0-20), P = .004.
      The DS group had a significant increase in postoperative hemorrhage compared with
      non-DS (10 [2.8%] vs 87 [1.2%], respectively), P = .024. However, the DS and non
      DS groups were comparable for respiratory complications (5 [1.4%] vs 106 [1.5%],
      respectively), P = .922. Median length of stay was significantly increased in the
      DS group (1 [interquartile range (IQR), 1-3]) compared with the non-DS group (1
      [IQR, 1-2]), P < .001. Median charges for hospital stay totaled $17,451 (IQR,
      $11,901-$24,949) for the DS group compared with $14,395 (IQR, $9739-$21,890) for
      the non-DS group, P < .001. Conclusion Across the United States, children with DS
      hospitalized for tonsillectomy have an increased length of stay and cost of care.
      These data also suggest an increased risk of postoperative hemorrhage during the
      initial admission without an increased risk of respiratory complications.

PMID- 28762291
TI  - Water permeability is a measure of severity in acute appendicitis.
AB  - Acute appendicitis is the most common indication for pediatric abdominal
      emergency surgery. Determination of the severity of appendicitis on clinical
      grounds is challenging. Complicated appendicitis presenting with perforation,
      abscess or diffuse peritonitis is not uncommon. The question remains why and when
      acute appendicitis progresses to perforation. The aim of this study was to assess
      the impact of water permeability on the severity of appendicitis. We show that
      AQP1 expression and water permeability in appendicitis correlate with the stage
      of inflammation and systemic infection parameters, leading eventually to
      perforation of the appendix. AQP1 is also expressed within the ganglia of the
      enteric nervous system and ganglia count increases with inflammation. Severity of
      appendicitis can be correlated with water permeability measured by AQP1 protein
      expression and increase of ganglia count in a progressive manner. This introduces
      the question if regulation of water permeability can present novel curative or
      ameliorating therapeutic options.

PMID- 28762293
TI  - The potential of FimH as a novel therapeutic target for the treatment of Crohn's
      disease.
AB  - INTRODUCTION: Crohn's disease (CD) is a life-long chronic disorder characterized
      by intestinal inflammation. Current treatments for CD are directed towards
      abnormal immune responses rather than the intestinal bacteria that trigger
      intestinal inflammation. Areas covered: Adherent-Invasive Escherichia coli (AIEC)
      bacteria abnormally colonize the ileal mucosa in a subgroup of CD patients. They
      can promote or perpetuate chronic inflammation and are therefore an interesting
      therapeutic target. Various strategies that target these E. coli strains have
      been developed to promote their intestinal clearance. Here, we review current
      AIEC-targeted strategies, especially anti-adhesive strategies, that are based on
      the development of FimH antagonists. We discuss their potential as personalized
      microbiota-targeted treatments for CD patients abnormally colonized by AIEC.
      Expert opinion: A large panel of mannose-derived FimH antagonists were tested for
      their ability to inhibit E. coli adhesion to host cells. Documented reports
      suggest that monovalent mannosides are promising candidates that could represent
      a complementary therapeutic strategy to prevent intestinal inflammation in the E.
      coli-colonized CD patient subgroup. Ongoing research continues to improve the
      pharmacokinetic properties of mannosides, and hopefully, clinical trials will be
      performed in CD patients in the near future.

PMID- 28762294
TI  - Relevant research from orthodontic journals.

PMID- 28762295
TI  - A constant conversation: tuning into and harmonizing the needs and priorities of
      the body and mind.
AB  - PURPOSE: Individuals rely upon many types of information to manage an illness,
      including information provided by their own bodies. This study investigated how
      people tune into and manage the flow of information from their bodies to manage
      their health. METHOD: We developed a platform for participants to share and
      collaboratively reflect on how they engaged in this dialogic process, in which
      participants contributed to a discussion on topics relating to body listening and
      body awareness. Though the study was open to anyone interested in or wanting to
      contribute to knowledge on "body listening," the social media recruitment focused
      on chronic conditions requiring self-care and having overlapping symptomatology,
      with chronic pain as the primary characteristic. A qualitative analysis method
      based on grounded theory was used to analyse the data. RESULTS: Six main themes
      emerged: learning the language, recognizing and heeding limits, experiencing
      emotional fatigue and despair, regulating the channel, moving from conflict to
      communication, and settling into an uneasy acceptance. CONCLUSION: The monitoring
      and filtering of information from one's body, and the appeasement of conflicting
      demands and voices, is difficult work. Knowledge of this process can be used in
      patient education and in the development of tools to support body listening.

PMID- 28762296
TI  - Current nutritional approaches in managing autism spectrum disorder: A review.
AB  - : The link between nutrition and autism spectrum disorder (ASD), which is a
      complex developmental disorder manifesting itself in significant delays or
      deviation in interaction and communication, has provided a fresh point of view
      and signals that nutrition may have a role in the aetiology of ASD, as well as
      play an active role in treatment by alleviating symptoms. OBJECTIVE: In this
      review study aimed at evaluating, with scientific and concrete proof, the current
      medical nutrition implementations on ASD, existing medical nutrition therapies
      have been addressed and their effects on ASD symptoms have been discussed in
      light of current research. METHODS: We reviewed articles regarding the medical
      nutritional therapy of autism on current nutritional approaches selected from
      PubMed, Science Direct, EBSCO, and databases about autism and nutrition. RESULTS:
      The research put forward that in individuals with ASD, while gluten-free/casein
      free and ketogenic diets, camel milk, curcumin, probiotics, and fermentable foods
      can play a role in alleviating ASD symptoms, consumption of sugar, additives,
      pesticides, genetically modified organisms, inorganic processed foods, and hard
      to-digest starches may aggravate symptoms. DISCUSSION: Further prospective
      controlled trials with large sample sizes are needed before recommendations can
      be made regarding the ideal ASD diet. This review emphasizes the value of
      identifying current nutritional approaches specific to individuals with ASD and
      integrating their effects on symptoms to the conversation and presents
      suggestions for future research designed to identify medical nutrition therapies
      targeting this population to better understand the link between ASD and
      nutrition.

PMID- 28762297
TI  - The association of USMLE Step 1 and Step 2 CK scores with residency match
      specialty and location.
AB  - BACKGROUND: For future physicians, residency programs offer necessary extended
      training in specific medical specialties. Medical schools benefit from an
      understanding of factors that lead their students to match into certain residency
      specialties. One such factor, often used during the residency application
      process, is scores on the USA Medical Licensing Exam (USMLE). OBJECTIVES: To
      determine the relationship between USMLE Step 1 and Step 2 Clinical Knowledge
      (CK) scores and students' residency specialty match, and the association between
      both USMLE scores and state of legal residency (Minnesota) at the time of
      admission with students staying in-state or leaving the state for residency
      program. DESIGN: USMLE scores and residency match data were analyzed from five
      graduating classes of students at the University of Minnesota Medical School (N =
      1054). RESULTS: A MANOVA found significant differences (p < 0.001) between
      residency specialties and both USMLE Step 1 and Step 2 CK scores, as well as the
      combination of the two. Students who matched in Dermatology had the highest mean
      USMLE scores overall, while students who matched in Family Medicine had the
      lowest mean scores. Students who went out of state for residency had
      significantly higher Step 1 scores (p = 0.027) than students who stayed in-state
      for residency, while there was no significant difference between the groups for
      Step 2 scores. A significant positive association was found between a student who
      applied as a legal resident of Minnesota and whether the student stayed in
      Minnesota for their residency program. CONCLUSIONS: Residency specialty match was
      significantly associated with USMLE Step 1 and USMLE Step 2 CK scores, as was
      staying in-state or leaving the state for residency. Students who were legal
      residents of the state at the time of application were more likely to stay in
      state for residency, regardless of USMLE score. ABBREVIATIONS: CK: Clinical
      knowledge; COMLEX: Comprehensive Osteopathic Medical Licensing Examination; GME:
      Graduate medical education; NRMP: National Resident Matching Program; UME:
      Undergraduate medical education; USMLE: United States Medical Licensing
      Examination.

PMID- 28762298
TI  - Cardiac myxoma: clinical characteristics, surgical intervention, intra-operative
      challenges and outcome.
AB  - OBJECTIVE: The objectives of this retrospective study were to characterize the
      clinical presentation, diagnostic findings, surgical approaches, intra-operative
      challenges and complications following the surgical treatment of cardiac myxoma
      in two of the largest referral hospitals in Jordan. METHODS: Medical records of
      all patients presented to the cardiology department during the period between
      1984 and 2016 were reviewed. Criteria for inclusion in the study were: (1)
      patients who were presented for cardiac evaluation due to symptoms suggestive of
      a primary cardiac problem, (2) completed medical records, including results of
      echocardiography suggestive of intra-cardiac occupying mass, (3) the surgical
      operation was undertaken and intra-operative data was available, (4) a
      histological diagnosis of myxoma was available and (5) the discharge status and
      follow-up data were available for at least 2 years after initial surgery.
      RESULTS: A total of 27 patients fulfilled the criteria for inclusion in the
      study. The average age was 42 years. Thirteen of the patients were females and 14
      patients were males. The most common clinical presentations were dyspnea (29.6%)
      and murmurs (22.2%). Non-specific signs, such as weight loss, fever, fatigue,
      arthralgia and anemia, were reported in 10 (37%) patients. Signs related to
      systemic embolization were reported in 9 (33.3%) of the patients, involving the
      upper and lower extremities (55.6%), brain ischemia and vision loss (54.4%).
      Tumors in all patients were successfully resected under cardiopulmonary bypass
      support. The tumor was pedunculated in 17 (62.9%) of the patients and the size of
      the tumors varied from 1 to 7 centimeters in diameter. The tumor was located in
      the left atrium in 21 patients (77.7%), in the right atrium in 4 patients
      (14.8%), in the right ventricular side of the septum in 1 patient (3.7%) and
      involving the tricuspid valve in 1 patient (3.7%). The left atrial approach was
      used in 3 patients, a right atrial approach in 4 patients and a bi-atrial
      approach in 20 patients. The most common concomitant cardiac pathology was
      coronary artery disease in 3 patients and an atrial septal defect in one patient.
      The most common intra-operative challenges were inter-atrial communication (2
      patients), large defect in the tricuspid valve leaflet (1 patient) and
      involvement of the inter-ventricular septum (1 patient). In the post-operative
      period, 1 patient suffered a stroke. In the post-operative period, the most
      common complications were stroke (1 patient) and recurrence of the tumor (2
      patients). CONCLUSION: The success rate after surgical removal of cardiac myxoma
      in this study was substantial and complications were rare.

PMID- 28762299
TI  - Congenital prothrombin defects: they are not only associated with bleeding but
      also with thrombosis: a new classification is needed.
AB  - OBJECTIVE: Congenital prothrombin deficiency is one of the rarest clotting
      disorders. It is commonly subdivided in Type I defects or cases of 'true'
      prothrombin deficiency characterized by a concomitant decrease in FII activity
      and antigen and in Type II or dysprothrombinemias, in which FII activity is low
      but FII antigen is normal or near normal. A bleeding tendency, often a severe
      one, is the hallmark of the two-defects even though the bleeding is usually less
      severe in the Type 2 defects or dysprothrombinemias. PATIENTS AND METHODS: An
      extensive search of published cases of prothrombin deficiency was carried out in
      Pubmed and Scopus. The search started in 2012, after the publication of the first
      family with dysprothrombinemia and venous thrombosis. A few additional families
      were found. RESULTS: Recent studies have demonstrated that the Type 2 defects are
      heterogeneous. Several heterozygous mutations involving the Arg596 residue of
      exon 14 have been demonstrated not be associated with a bleeding tendency but,
      surprisingly, with venous thromboses. Mutations in close areas of prothrombin
      have failed to show the same pattern. CONCLUSIONS: These observations have
      required a reclassification of prothrombin defects. To the Type I and Type II
      defects, a Type III has to be added characterized by the absence of bleeding and
      the presence of venous thrombosis. It is not clear yet if this special variant of
      Type II defect is limited to the Arg596 mutations or if other residues may be
      involved.

PMID- 28762301
TI  - In Reference to "A New Theory for Meniere's Disease".

PMID- 28762300
TI  - Social justice, access and quality of healthcare in an age of austerity: users'
      perspective from rural Iceland.
AB  - Iceland is sparsely populated but social justice and equity has been emphasised
      within healthcare. The aim of the study is to examine healthcare services in
      Fjallabyggd, in rural northern Iceland, from users' perspective and evaluate
      social justice, access and quality of healthcare in an age of austerity. Mixed
      method approach with transformative design was used. First, data were collected
      with questionnaires (response rate of 53% [N=732] in 2009 and 30% [N=415] in
      2012), and analysed statistically, followed by 10 interviews with healthcare
      users (2009 and 2014). The results were integrated and interpreted within
      Bronfenbrenner's Ecological Model. There was significantly less satisfaction with
      accessibility and variety of healthcare services in 2012 after services
      downsizing. Solid primary healthcare, good local elderly care, some freedom in
      healthcare choice and reliable emergency services were considered fundamental for
      life in a rural area. Equal access to healthcare is part of a fundamental human
      right. In times of economic downturn, people in rural areas, who are already
      vulnerable, may become even more vulnerable and disadvantaged, seriously
      threatening social justice and equity. With severe cutbacks in vitally important
      healthcare services people may eventually choose to self-migrate.

PMID- 28762302
TI  - Highlights from the Current Issue: August 2017.

PMID- 28762303
TI  - Beyond Phonosurgery: Considerations for Patient-Reported Outcomes and Speech
      Therapy in Transgender Vocal Feminization.

PMID- 28762304
TI  - Identification of two novel mutations in RASGRP2 affecting platelet CalDAG-GEFI
      expression and function in patients with bleeding diathesis.
AB  - The RASGRP2 gene encodes the Ca2+ and DAG-regulated guanine nucleotide exchange
      factor I (CalDAG-GEFI), which plays a key role in integrin activation in
      platelets and neutrophils. We here report two new RASGRP2 variants associated
      with platelet dysfunction and bleeding in patients. The homozygous patients had
      normal platelet and neutrophil counts and morphology. Platelet phenotyping
      showed: prolonged PFA-100 closure times; normal expression of major glycoprotein
      receptors; severely reduced platelet aggregation response to ADP and collagen
      (both patients); aggregation response to PAR1 and arachidonic acid markedly
      impaired in one patient; PMA-induced aggregation unaffected; platelet secretion,
      clot retraction, and spreading minimally affected. Genetic analysis identified
      two new homozygous variants in RASGRP2: c.706C>T (p.Q236X) and c.887G>A
      (p.C296Y). In both patients, CalDAG-GEFI protein was not detectable in platelet
      lysates, and platelet alphaIIbbeta3 activation, as assessed by fibrinogen
      binding, was greatly impaired in response to all agonists except PMA. Patient
      neutrophils showed normal integrin expression, but impaired Mn2+-induced
      fibrinogen binding. In summary, we have identified two new RASGRP2 mutations that
      can be added to this rapidly growing form of inherited platelet function
      disorder.

PMID- 28762305
TI  - Promoting Community Conversations About Research to End Suicide: learning and
      behavioural outcomes of a training-of-trainers model to facilitate grassroots
      community health education to address Indigenous youth suicide prevention.
AB  - Alaska Native (AN) youth suicide remains a substantial and recalcitrant health
      disparity, especially in rural/remote communities. Promoting Community
      Conversations About Research to End Suicide (PC CARES) is a community health
      intervention that responds to the need for culturally responsive and evidence
      supported prevention practice, using a grassroots approach to spark multilevel
      and community-based efforts for suicide prevention. This paper describes
      theoretical and practical considerations of the approach, and assesses the
      feasibility and preliminary learning and behavioural outcomes of the training-of
      trainers model. It details the training of a first cohort of intervention
      facilitators in Northwest Alaska (NWA). Thirty-two people from 11 NWA village
      communities completed the PC CARES facilitator training, preparing them to
      implement the intervention in their home communities. Facilitator pre-post
      surveys focused on readiness to facilitate, a group quiz assessed participants'
      understanding of relevant research evidence, and practice facilitation exercises
      demonstrated competency. Curriculum fidelity and accuracy scores were calculated
      using audio recordings from learning circles conducted by facilitators in their
      home communities. Facilitator reflections describe the successes of the model and
      identify several areas for improvement. As of March 2017, 20 of the 32 trained
      facilitators in 10 of the 11 participating villages have hosted 54 LCs, with a
      total of 309 unique community members. Coding of these LCs by 2 independent
      raters indicate acceptable levels of fidelity and accurate dissemination of
      research evidence by facilitators. Facilitator reflections were positive overall,
      suggesting PC CARES is feasible, acceptable and potentially impactful as a way to
      translate research to practice in under-resourced, rural AN communities. PC CARES
      represents a practical community education and mobilisation approach to
      Indigenous youth suicide prevention that displays preliminary success in learning
      and behavioural outcomes of local facilitators.

PMID- 28762306
TI  - Emerging Targets and Latest Proteomics Based Therapeutic Approaches in
      Neurodegenerative Diseases.
AB  - Protein homeostasis (proteostasis) is achieved by the interplay among various
      components and pathways inside a cell. Dysfunction in proteostasis leads to
      protein misfolding and aggregation which is ubiquitously associated with many
      neurodegenerative disorders, although the exact role of these aggregate in the
      pathogenesis remains unknown. Many neurodegenerative diseases, including
      Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic
      lateral sclerosis, and others are characterized by the conversion of specific
      protein aggregates into protein inclusions and/or plaques in degenerating brains.
      Apart from the conventional disease specific proteins, such as amyloid-beta,
      alpha - synuclein, huntingtin protein, and prions that are known to aggregate, a
      number of other proteins play a vital role in aggravating the disease condition.
      In this review, we discuss the disease etiology, mechanism, the role of various
      pathways, molecular machinery including molecular chaperones, protein degradation
      pathways, and the active formation of inclusions in various neurodegenerative
      diseases. We also highlight the approaches, strategies, and methods that have
      been used for the treatment of these complex diseases over the years and the
      efforts that have potential in the near future.

PMID- 28762307
TI  - Oxidative Stress and Inflammation: Their Role in the Pathogenesis of Peripheral
      Artery Disease with or Without Type 2 Diabetes Mellitus.
AB  - Peripheral Artery Disease (PAD), a common vascular disease, has been associated
      with increased Cardiovascular (CV) morbidity and mortality as well as all-cause
      death. Type 2 Diabetes Mellitus (T2DM) predisposes to PAD development. In T2DM
      patients, PAD further increases the risk for CV disease and death as well as foot
      morbidity and microvascular complications. The present narrative review discusses
      the role of oxidative stress and inflammation in the pathophysiology of PAD with
      or without the presence of T2DM. The effects of lifestyle measures (i.e. diet,
      physical activity and smoking cessation) and drug treatment on markers of
      oxidative stress and inflammation are also considered. Further research should
      establish the clinical implications of such effects as well as the clinical use
      of antioxidants and anti-inflammatory drugs in PAD.

PMID- 28762308
TI  - The Nephroprotective Effect of N-Acetyl-L-Cysteine and Atorvastatin against
      Imipenem induced Nephrotoxicity.
AB  - BACKGROUND AND OBJECTIVE: Imipenem has played an important role in the treatment
      of broad-spectrum bacterial infection. However, nephrotoxicity due to imipenem
      remains an important clinical challenge. The aim of this study is to test the
      hypothesis stating that N-acetyl-L-cysteine (NAC) and atorvastatin possess a
      nephroprotective effect against imipenem-induced nephrotoxicity. METHODS: Adult
      Sprague Dawley rats were randomly assigned into six groups (n=8-10 rats/group;
      total n=55). The groups were (control, imipenem only, NAC only, atorvastatin
      only, NAC with imipenem, and atorvastatin with imipenem). Rats were treated with
      NAC or atorvastatin for six weeks. Serum and urinary creatinine and blood urea
      nitrogen (BUN) levels were measured. Additionally, urinary protein, urinary
      glucose and kidney levels of oxidants/antioxidants biomarkers were measured.
      RESULTS: The administration of 300mg/kg/d imipenem induced nephrotoxicity as
      indicated by the significant reduction of serum creatinine, serum BUN and
      calculated GFR in the imipenem only-treated group compared to the control. These
      effects of imipenem were normalized by either NAC or atorvastatin. Moreover, the
      levels of catalase, superoxide dismutase and glutathione peroxidase were
      significantly reduced in the imipenem group. However, pre-administration of NAC
      and atorvastatin neutralized the levels of these enzymes and protected against
      imipenem-induced nephrotoxicity. CONCLUSION: We concluded that the pre
      administration of either NAC or atorvastatin protects the kidneys from imipenem
      induced nephrotoxicity, through their antioxidant effects.

PMID- 28762309
TI  - Histone Deacetylase Inhibitors in Tumor Immunotherapy.
AB  - With an increasing understanding of the antitumor immune response, considerable
      progress has been made in the field of tumor immunotherapy in the last decade.
      Inhibition of HDACs represents a new strategy in tumor therapy and HDAC
      inhibitors have been recently developed and validated as potential antitumor
      drugs. In addition to the direct antitumor effects, HDAC inhibitors have been
      found to have the ability to improve tumor recognition by immune cells that may
      contribute to their antitumor activity. These immunomodolutory effects are
      desirable, and their in-depth comprehension will facilitate the design of novel
      regimens with improved clinical efficacy. In this review, we summarize recent
      advances in the understanding of how HDAC inhibitors alter immune process and
      discuss their effects on various cytokines. We also discuss the challenges to
      optimize the use of these inhibitors as immune modulators in cancer treatment,
      which may be helpful for designing tumor immunotherapy trials involving HDAC
      inhibitors.

PMID- 28762311
TI  - Therapeutic Potential of Co-enzyme Q10 in Retinal Diseases.
AB  - BACKGROUND: Coenzyme Q10 (CoQ10) plays a critical role in mitochondrial oxidative
      phosphorylation by serving as an electron carrier in the respiratory electron
      transport chain. CoQ10 also functions as a lipid-soluble antioxidant by
      protecting lipids, proteins and DNA damaged by oxidative stress. CoQ10 deficiency
      has been associated with a number of human diseases in which CoQ10
      supplementation therapy has been effective in slowing or reversing pathological
      changes. Oxidative stress is a major contributory factor in the process of
      retinal degeneration. METHOD: The related literature was reviewed through
      searching PubMed using keywords: CoQ10, CoQ10 and oxidative stress, CoQ10 and
      retinal degeneration. The functions of CoQ10 were summarized and its use in the
      treatment of age-related macular degeneration and glaucoma highlighted. The
      therapeutic potential of CoQ10 for other retinal diseases was also discussed.
      RESULTS: CoQ10 has been applied in different types of neurodegeneration. CoQ10 is
      detectable in retina and declines with ageing. Early studies showed treatment of
      CoQ10 improved visual function in patients with age-related macular degeneration.
      In glaucomatous models, CoQ10 exposure protected ganglion cell death from
      environmental stress; in glaucoma patients, CoQ10 treatment demonstrated
      beneficial effects on function of inner retina and enhancement of visual cortical
      response. Since oxidative stress also plays a critical role in the pathogenesis
      of diabetic retinopathy and retinitis pigmentosa, CoQ10 is a therapeutic target
      for both conditions. CONCLUSION: A wide range of evidence supports a role of
      CoQ10 in retinal diseases through inhibiting production of reactive oxygen
      species and protecting neuroretinal cells from oxidative damage.

PMID- 28762310
TI  - Sarcopenia, aging and prospective interventional strategies.
AB  - Sarcopenia, or age-related muscle decline, occurs in most organisms and burdens
      both human health and the healthcare system. As our population ages, additional
      options for treating sarcopenia are needed. Mitochondrial dysfunction is
      implicated in the onset of sarcopenia, so therapies directed at improving
      mitochondrial function in muscle should be considered. Many naturally-occurring
      compounds, derived from commonly consumed foods, possess anti-sarcopenic effects,
      such asnicotinamide riboside, tomatidine, and Urolithin A. These naturally
      occurring compounds can improve mitochondrial health and efficiency by modulating
      mitochondrial biogenesis, cellular stress resistance, or mitophagy. Further
      research should assess whether compounds that improve mitochondrial health can
      attenuate sarcopenia in humans.

PMID- 28762312
TI  - Cadmium, Organ Toxicity and Therapeutic Approaches: A Review on Brain, Kidney and
      Testis Damage.
AB  - BACKGROUND: Cadmium (Cd) is a heavy metal particularly hazardous for human
      health, as it is highly diffused and, therefore, a ubiquitous environmental
      toxicant. In fact, in the general population, the main sources of exposure are
      food, cigarette smoking, inhalation of ambient air, drinking water, contaminated
      soil or dust. Furthermore, an occupational exposure usually involves human during
      mining, fume inhalation or manufacturing nickel-cadmium battery, electroplating
      and paint pigments that utilize Cd. METHODS: We undertook a structured search in
      literature about Cd. This metal is noxious on the cells of many organs, among
      which the kidney, the testis and the brain will be considered in this review.
      RESULTS: The toxic effects induced by Cd include many specific mechanisms, such
      as the oxidative stress, cellular death and inflammation. As no specific therapy
      for the prevention or treatment of the morbidity and mortality associated with Cd
      exposure is available, the state of the art of the therapeutic approaches is
      illustrated. CONCLUSION: Nowadays, a therapy able to counteract Cd toxicity is
      still lacking and the development of new therapeutic agents is requested.

PMID- 28762313
TI  - Adoptive immunotherapy for B-cell malignancies using CD19-targeted chimeric
      antigen receptor T-cells: A systematic review of efficacy and safety.
AB  - BACKGROUND: Adoptive infusion of chimeric antigen receptor transduced T-cells
      (CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as
      evidenced by recently published and unpublished clinical results. OBJECTIVE: In
      this report, we performed a meta-analysis to evaluate the efficacy and side
      effects of CAR-T on relapsed B-cell malignancies, including leukemia and
      lymphoma. METHODS: Clinical studies investigating efficacy and safety of CAR-T in
      acute and chronic lymphocytic leukemia and lymphoma were identified by searching
      PubMed and EMBASE. Outcomes of efficacy subjected to analysis were the rates of
      complete remission (CR) and partial remission (PR). The safety parameters were
      the prevalence of adverse effects including fever, hypotension, and acute renal
      failure. Meta analyses were performed using R software. Weighted hazard ratio
      (HR) with 95% confidence intervals was calculated for each outcome. Fixed or
      random-effects models were employed depending on the heterogeneity across the
      included studies. RESULTS: Nineteen published clinical studies, with a total of
      391 patients were included for the meta-analysis. The pooled rate of complete
      remission was 55% (95% CI 41%-69%); the pooled rate of partial remission was 25%
      (95% CI: 19%-33%). The prevalence of fever was 62% (95% CI: 41%-79%); the
      hypotension was 22% (95% CI: 15%-31%); acute renal failure was 24% (95% CI: 16%
      34%). All adverse effects were manageable and no death was reported due to
      toxicity. CONCLUSION: CD19-targeted CAR-T is an effective modality in treating
      refractory B-cell malignancies including acute and chronic lymphatic leukemia,
      Hodjkin's and non-Hodjkin's lymphoma.

PMID- 28762315
TI  - Targeting Protective Catalase of Tumor Cells with Cold Atmospheric Plasma-
      Activated Medium (PAM).
AB  - BACKGROUND: Application of cold atmospheric plasma to medium generates "plasma
      activated medium" that induces apoptosis selectively in tumor cells and that has
      an antitumor effect in vivo. The underlying mechanisms are not well understood.
      OBJECTIVE: Elucidation of potential chemical interactions within plasma-activated
      medium and of reactions of medium components with specific target structures of
      tumor cells should allow to define the active principle in plasma activated
      medium. METHODS: Established knowledge of intercellular apoptosis-inducing
      reactive oxygen/nitrogen species-dependent signaling and its control by membrane
      associated catalase and SOD was reviewed. Model experiments using extracellular
      singlet oxygen were analyzed with respect to catalase inactivation and their
      relevance for the antitumor action of cold atmospheric plasma. Potential
      interactions of this tumor cell-specific control system with components of plasma
      activated medium or its reaction products were discussed within the scope of the
      reviewed signaling principles. RESULTS: None of the long-lived species found in
      plasma-activated medium, such as nitrite and H2O2, nor OCl- or .NO seemed to have
      the potential to interfere with catalase-dependent control of apoptosis-inducing
      signaling of tumor cells when acting alone. However, the combination of H2O2 and
      nitrite might generate peroxynitrite. The protonation of peroxnitrite to
      peroxynitrous acid allows for the generation of hydroxyl radicals that react with
      H2O2, leading to the formation of hydroperoxide radicals. These allow for singlet
      oxygen generation and inactivation of membrane-associated catalase through an
      autoamplificatory mechanism, followed by intercellular apoptosis-inducing
      signaling. CONCLUSION: Nitrite and H2O2 in plasma-activated medium establish
      singlet oxygen-dependent interference selectively with the control system of
      tumor cells.

PMID- 28762316
TI  - Hydrogen Peroxide and Beyond-the Potential of High-voltage Plasma-activated
      Liquids Against Cancerous Cells.
AB  - BACKGROUND: The use of plasma-activated liquids such as PBS, medium or simply
      plasma-activated water (PAW) has been receiving increasing attention for
      applications in cancer treatments. Amongst the reactive species contained in
      these solutions, hydrogen peroxide appears to play a pivotal role in causing
      cytotoxic effects. H2O2 concentrations can be correlated with reduced cell
      viability and growth and used as an indicator of the potential efficacy of a
      plasma-activated liquid. OBJECTIVE: To investigate the cytotoxic mediators
      generated in water specific to high-voltage DBD-ACP. METHOD: Using a high-voltage
      dielectric barrier atmospheric cold plasma (DBD-ACP) system, we examined PAW
      mediated cytotoxic effects on different mammalian cell lines employing a set-up
      where short-lived reactive species can be discounted and activated liquids with
      long-term stability are generated. RESULTS: The PAW potency could be modulated
      using voltage level, treatment time and post-treatment storage time and target
      related characteristics such as surface to volume ratio. All of these parameters
      effected cell viability in a hydrogen peroxide concentration correlated manner.
      The susceptibility of two cancer cell lines to PAW was similar to that observed
      for two non-cancer cell lines and the toxicity of plasma-activated water exceeded
      that of the corresponding hydrogen peroxide concentrations. CONCLUSION: In
      cytotoxic plasma activated water an essential role for H2O2 has been demonstrated
      multi-fold, yet further contributing factors are apparent and remain to be
      identified.

PMID- 28762317
TI  - Effects of Plasma Activated Medium on Head and Neck FaDu Cancerous Cells:
      Comparison of 3D and 2D Response.
AB  - OBJECTIVE: The aim of this work is to investigate the inhibitory effect of Plasma
      Activated Medium (PAM) on Head and Neck cancerous cells (FaDu). The response of
      FaDu cells in monolayer cultures and Multi Cellular Tumor Spheroids (MCTS) after
      treatment with different PAMs will be compared. BACKGROUND: Head and Neck
      squamous cell carcinoma is a widespread cancer that responds poorly to anticancer
      treatments such as chemotherapy and radiotherapy. Nowadays there is a growing
      interest in cold plasmas and their applications in cancer therapy. METHODS: A
      homemade helium plasma jet is used to produce PAM. The effects of PAM and
      hydrogen peroxide H2O2 on FaDu 2D cells cultures and MCTS were characterized by
      evaluating the cell viability with PrestoBlue test and by measuring the size of
      MCTS. RESULTS: One treatment with PAM induce cell detachment from MCTS since the
      first day in a PAM exposure dependent manner. This is due to the presence of H2O2
      in PAM. However, a rapid spheroids regrowth is observed attributed to a
      resistance of FaDu cells to H2O2. After multiple treatments of MCTS with PAM we
      obtained an inhibition of cell growth. MCTS are brought out when comparing PAM
      effect on 2D versus MCTS. Inversely, PAM induces cell death in the case of 2D
      cell culture. CONCLUSION: PAM may be considered as a potentially efficient agent
      in the therapy of head and neck cancer. We also point out that MCTS is a more
      valuable model than 2D cell culture for the evaluation of the anti-cancer
      activity of PAM.

PMID- 28762318
TI  - The Application of the Cold Atmospheric Plasma-Activated Solutions in Cancer
      Treatment.
AB  - BACKGROUND: Over the past five years, the cold atmospheric plasma-activated
      solutions (PAS) have shown their promissing application in cancer treatment.
      Similar as the common direct cold plasma treatment, PAS shows a selective anti
      cancer capacity in vitro and in vivo. However, different from the direct cold
      atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be
      used without dependence on a CAP device. The research on PAS is gradually
      becoming a hot topic in plasma medicine. OBJECTIVES: In this review, we gave a
      concise but comprehensive summary on key topics about PAS including the
      development, current status, as well as the main conclusions about the anti
      cancer mechanism achieved in past years. The approaches to make strong and stable
      PAS are also summarized.

PMID- 28762319
TI  - Quantification of Sulfotransferases 1A1 and 1A3/4 in Tissue Fractions and Cell
      Lines by Multiple Reaction Monitoring Mass Spectrometry.
AB  - BACKGROUND: Within the sulfotransferase (SULT) superfamily of metabolic enzymes,
      SULT1A1 and 1A3/4 isoforms are of particular interest, due to their abilities to
      catalyze the sulfation of phenolic endobiotics and xenobiotics. Although the
      difference in their substrate specificity is well documented, an isoform-specific
      quantification method is still not available. OBJECTIVE: To detect and quantify
      SULT1A1 and 1A3/4 in S9 fractions and cell lines using targeted mass spectrometry
      based proteomics. METHOD: Samples were tryptically digested, and signature
      peptides were quantified using liquid chromatography- multiple reaction
      monitoring mass spectrometry (LC-MRM/MS). Stable isotopelabeled (SIL) peptides
      were used as internal and calibration standards. SULT1A1 and SULT1A3/4 were
      quantified in various S9 fractions and cell line samples. RESULTS: Intraday and
      interday variabilities were low for relative quantification in S9 and cell line
      matrices (<8%). Expression profiles were validated using Western blot analysis of
      S9 fractions and lentiviral transduced SULT1A-overexpressing cell lines.
      CONCLUSION: A reproducible method for simultaneous quantification of SULT1A1 and
      SULT1A3/4 in S9 fractions and cell line samples was established and validated.

PMID- 28762320
TI  - Neuropsychological Clustering in Bipolar and Major Depressive Disorder.
AB  - OBJECTIVES: Cognitive dysfunction is a key feature of major depressive (MDD) and
      bipolar (BD) disorders. However, rather than a single cognitive profile
      corresponding to each diagnostic categories, recent studies have identified
      significant intra- and cross-diagnostic variability in patterns of cognitive
      impairment. The goal of this study was to contribute to the literature on
      cognitive heterogeneity in mood disorders by identifying cognitive subprofiles in
      a population of patients with MDD, BD type I, BD type II, and healthy adults.
      METHODS: Participants completed a neuropsychological battery; scores were
      converted into Z-scores using normative data and submitted to hierarchical
      cluster analysis. RESULTS: Three distinct neuropsychological clusters were
      identified: (1) a large cluster containing mostly control participants, as well
      as some patients with BD and MDD, who performed at above-average levels on all
      neuropsychological domains; (2) a cluster containing some patients from all
      diagnostic groups, as well as healthy controls, who performed worse than cluster
      1 on most tasks, and showed impairments in motor inhibition and verbal fluency;
      (3) a cluster containing mostly patients with mood disorders with severe
      impairments in verbal inhibition and cognitive flexibility. CONCLUSIONS: These
      findings revealed multiple cognitive profiles within diagnostic categories, as
      well as significant cross-diagnostic overlap, highlighting the importance of
      developing more specific treatment approaches which consider patients'
      demographic and cognitive profiles in addition to their diagnosis. (JINS, 2017,
      23, 584-593).

PMID- 28762314
TI  - Insights Into Nicotinic Receptor Signaling in Nicotine Addiction: Implications
      for Prevention and Treatment.
AB  - BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop
      ligandgated ion-channel (LGIC) superfamily, which also includes the GABA,
      glycine, and serotonin receptors. Many nAChR subunits have been identified and
      shown to be involved in signal transduction on binding to them of either the
      neurotransmitter acetylcholine or exogenous ligands such as nicotine. The nAChRs
      are pentameric assemblies of homologous subunits surrounding a central pore that
      gates cation flux, and they are expressed at neuromuscular junctions throughout
      the nervous system. METHODS AND RESULTS: Because different nAChR subunits
      assemble into a variety of pharmacologically distinct receptor subtypes, and
      different nAChRs are implicated in various physiological functions and
      pathophysiological conditions, nAChRs represent potential molecular targets for
      drug addiction and medical therapeutic research. This review intends to provide
      insights into recent advances in nAChR signaling, considering the subtypes and
      subunits of nAChRs and their roles in nicotinic cholinergic systems, including
      structure, diversity, functional allosteric modulation, targeted knockout
      mutations, and rare variations of specific subunits, and the potency and
      functional effects of mutations by focusing on their effects on nicotine
      addiction (NA) and smoking cessation (SC). Furthermore, we review the possible
      mechanisms of action of nAChRs in NA and SC based on our current knowledge.
      CONCLUSION: Understanding these cellular and molecular mechanisms will lead to
      better translational and therapeutic operations and outcomes for the prevention
      and treatment of NA and other drug addictions, as well as chronic diseases, such
      as Alzheimer's and Parkinson's. Finally, we put forward some suggestions and
      recommendations for therapy and treatment of NA and other chronic diseases.

PMID- 28762321
TI  - Rapid Determination of Amino Acids in Beer, Red Wine, and Donkey-Hide Gelatin by
      Gradient Elution of HPLC: From Micellar Liquid Chromatography to High Submicellar
      Liquid Chromatography.
AB  - Amino acids (AAs) in beer, red wine, and donkey-hide gelatin were rapidly
      determined by gradient LC elution from micellar LC to high submicellar LC. Mobile
      phase A was a 0.075 M sodium dodecyl sulfate solution containing 20 mM ammonium
      acetate with a pH value adjusted to 3.5 with acetic acid solution, and mobile
      phase B was acetonitrile. Optimized chromatographic conditions were as follows:
      mobile phase B increased from 25 to 60% (v/v) in 30 min and the use of a Venusil
      XBP C18 column (5 um, 250 * 4.6 mm) as the stationary phase, with a column
      temperature of 35 degrees C, flow rate of 1.2 mL/min, and detection wavelength of
      266 nm. The results indicated good linearity (r2 >= 0.9924). The intraday
      precision of the retention time was RSD <= 1.1%, whereas interday was RSD <=
      3.2%; intraday precision of the peak area was RSD <= 3.3%, whereas interday was
      RSD <= 4.9%. The range of recovery was 94.6-102.4%. The RSDs of the retention
      time for the AAs for the different samples were 0.04-0.31%.

PMID- 28762322
TI  - Optimized Mass Spectrometry-Based Metabolite Extraction and Analysis for the
      Geographical Discrimination of White Rice (Oryza sativa L.): A Method Comparison
      Study.
AB  - In this study, we examined the effects of different extraction methods for the GC
      MS- and LC-MS-based metabolite profiling of white rice (Oryza sativa L.). In
      addition, the metabolite divergence of white rice cultivated in either Korea or
      China was also evaluated. The discrimination analysis of each extraction method
      for white rice from Korea and China and the corresponding discriminatory markers
      were estimated by unpaired t-test, principal component analysis, k-means cluster
      analysis, partial least-squares discriminant analysis (PLS-DA), and random forest
      (RF). According to the prediction parameters obtained from PLS-DA and RF
      classifiers as well as features that could be identified, the extraction method
      using 75% isopropanol heated at 100 degrees C coupled with LC-MS analysis was
      confirmed to be superior to the other extraction methods. Noticeably,
      lysophospholipid concentrations were significantly different in white rice
      between Korea and China, and they are novel markers for geographical
      discrimination. In conclusion, our study suggests an optimized extraction and
      analysis method as well as novel markers for the geographical discrimination of
      white rice.

PMID- 28762323
TI  - Rifaximin Stability: A Look at UV, IR, HPLC, and Turbidimetry Methods.
AB  - The study of the stability of medicines is mandated by the International
      Conference on Harmonization and the World Health Organization. Rifaximin, an
      antimicrobial marketed in the form of tablets, has no record of stability
      studies. Thus, the objective of the present work was to investigate the behavior
      and stability of rifaximin tablets for 6 months under simultaneous conditions of
      temperature and humidity by UV, IR, HPLC, and turbidimetry techniques. After 6
      months of stability study, rifaximin tablets were shown to obey zero-order
      kinetics when analyzed by physicochemical methods and second-order kinetics when
      analyzed by a microbiological method. However, the UV method was not suitable for
      the evaluation of rifaximin. IR, HPLC, and turbidimetry methods can already be
      used to evaluate the stability of rifaximin tablets. It is important to analyze
      products with more than one type of method before releasing results mainly in the
      case of antimicrobial products in which the association of physicochemical and
      microbiological techniques must be a rule. Rifaximin tablets can be considered
      stable after 6 months under conditions of 40 +/- 2 degrees C and 75 +/- 5%
      relative humidity.

PMID- 28762324
TI  - Interlaboratory Comparison of Methods Determining the Botanical Composition of
      Animal Feed.
AB  - A consortium of European enterprises and research institutions has been engaged
      in the Feed-Code Project with the aim of addressing the requirements stated in
      European Union Regulation No. 767/2009, concerning market placement and use of
      feed of known and ascertained botanical composition. Accordingly, an
      interlaboratory trial was set up to compare the performance of different assays
      based either on optical microscope or DNA analysis for the qualitative and
      quantitative identification of the composition of compound animal feeds. A
      tubulin-based polymorphism method, on which the Feed-Code platform was developed,
      provided the most accurate results. The present study highlights the need for the
      performance of ring trials for the determination of the botanical composition of
      animal feeds and raises an alarm on the actual status of analytical inaccuracy.

PMID- 28762325
TI  - Activation of Vimentin Is Critical to Promote a Metastatic Potential of
      Cholangiocarcinoma Cells.
AB  - Cholangiocarcinoma (CCA) is a highly metastatic tumor, and the majority of
      patients with CCA have a short survival time because there are no available
      effective treatments. Hence, a better understanding regarding CCA metastasis may
      provide an opportunity to improve the strategies for treatment. A comparison
      study between the highly metastatic cells and their parental cells is an approach
      to uncover the molecular mechanisms underlying the metastatic process. In the
      present study, a lung metastatic CCA cell line, KKU-214L5, was established by the
      in vivo selection of the tail vein-injected mouse model. KKU-214L5 cells
      possessed mesenchymal spindle-like morphology with higher migration and invasion
      abilities in vitro than the parental cells (KKU-214). KKU-214L5 also exhibited
      extremely aggressive lung colonization in the tail vein-injected metastatic
      model. Epithelial-mesenchymal transition (EMT) was clearly observed in KKU-214L5
      cells. Significant downregulation of epithelial markers (ZO-1 and claudin-1),
      with unique upregulation of E-cadherin and mesenchymal markers (vimentin, beta
      catenin, and slug), was observed in KKU-214L5. Increasing MMP-2 and MMP-9
      activities and CD147 expression reflected the high invasion activity in KKU-214L5
      cells. Suppression of vimentin using siRNA significantly decreased the migration
      and invasion capabilities of KKU-214L5 to almost the basal levels of the parental
      cells without any change on the expression levels of other EMT markers and the
      activities of MMPs. These results suggest that vimentin activation is essential
      to potentiate the metastatic characters of CCA cells, and suppression of vimentin
      expression could be a potential strategy to improve the treatment of CCA, a
      highly metastatic cancer.

PMID- 28762326
TI  - Long Noncoding RNA Urothelial Carcinoma-Associated 1 Promotes the Proliferation
      and Metastasis of Human Lung Tumor Cells by Regulating MicroRNA-144.
AB  - Long noncoding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) has gained
      more attention in recent years due to its oncogenic roles in various cancers.
      MicroRNA-144 (miR-144) participates in the regulation of the growth of many
      cancer cells. This study investigated the interaction between lncRNA UCA1 and miR
      144 in lung cancer cells. The potential downstream protein of miR-144 was also
      assessed. Our results found that lncRNA UCA1 was highly expressed in human lung
      cancer A549, H517, H4006, H1299, and H1650 cells compared to normal embryonic
      lung WI-38 and HEL-1 cells. Knockdown of lncRNA UCA1 significantly inhibited lung
      cancer A549 cell viability, migration, invasion, and cell cycle progression, but
      promoted cell apoptosis. Besides, we found that lncRNA UCA1 was bound to miR-144.
      miR-144 participated in the regulation effects of lncRNA UCA1 on A549 cell
      viability, migration, invasion, cell cycle transition, and cell apoptosis. In
      addition, Pre-B-cell leukemia homeobox 3 (PBX3) was found to be a direct target
      gene of miR-144. Overexpression of PBX3 promoted A549 cell proliferation and
      metastasis. Suppression of PBX3 had an opposite effect.

PMID- 28762327
TI  - Comparative Study Between Zero-Order Spectra-Processing and Ratio Spectra
      Manipulating Methods Applied for the Determination of Isoxsuprine Hydrochloride
      in the Presence of Its Oxidative Degradation Product.
AB  - Four accurate, precise, and validated stability-indicating spectrophotometric
      methods handling either zero-order spectra or ratio spectra have been developed
      and compared for the analysis of isoxsuprine hydrochloride (ISX) in the presence
      of its oxidative degradation product. The first two methods processed zero-order
      spectra, namely graphical absorbance ratio or Q-Analysis and area under the
      curve, whereas the third and fourth methods manipulated ratio spectra, namely the
      ratio difference spectrophotometric method and derivative ratio. The proposed
      methods showed good linearity in the range of 2-23 ug/mL. The methods were tested
      for specificity using laboratory-prepared mixtures containing the drug and its
      degradation product. The proposed methods were applied for the determination of
      ISX in Vascular tablets and the obtained results were acceptable, with small
      percentage RSD values. The validity of the proposed procedures was further
      assessed by applying the standard addition technique, which showed no
      interference from excipients. The obtained results were statistically compared
      with those obtained by the reported method, showing no significant differences
      when t- and F-tests were applied.

PMID- 28762328
TI  - Emodin Induces Apoptosis of Colon Cancer Cells via Induction of Autophagy in a
      ROS-Dependent Manner.
AB  - Recent studies revealed that emodin extracted from Chinese herbs exhibits an
      anticancer effect on different cancer types, including colon cancer. However, the
      mechanism is not well understood. In our study, we confirmed that emodin
      treatment inhibited cell viability and induced apoptosis in colon cancer cells.
      Further experiments found that emodin was also able to induce autophagy, which is
      indispensible for apoptosis induced by emodin. More interestingly, emodin
      treatment also results in mitochondrial dysfunction and ROS accumulation in colon
      cancer cells. Finally, we stressed that ROS accumulation is essential for
      autophagy and apoptosis induced by emodin. In conclusion, emodin induces
      apoptosis in colon cancer cells through induction of autophagy, during which ROS
      generation is of the essence. Our findings improve understanding of emodin's
      effect on colon cancer suppression and provide a new theoretical basis for colon
      cancer therapy.

PMID- 28762329
TI  - First Report for Determination of d-Penicillamine in the Presence of Tryptophan
      Using a 2-Chlorobenzoyl Ferrocene/Ag-Supported ZnO Nanoplate-Modified Carbon
      Paste Electrode.
AB  - In this work, a carbon paste electrode modified with Ag-ZnO nanoplates and 2
      chlorobenzoyl ferrocene was prepared and applied for the determination of d
      penicillamine in the presence of tryptophan. The morphologies of Ag-ZnO
      nanoplates were examined by scanning electron microscopy. It was found that under
      an optimum condition (pH 7.0), the oxidation of d-penicillamine at the surface of
      such an electrode occurs at a potential about 165 mV less positive than that of
      an unmodified carbon paste electrode. The diffusion coefficient (D = 7.6 * 10-6
      cm2/s) and the electron transfer coefficient (alpha = 0.54) for d-penicillamine
      oxidation were also determined. The proposed method exhibited a wide linear
      dynamic range of 0.03-250.0 uM, with an LOD (S/N = 3) of 0.015 uM. Moreover, the
      modified electrode exhibited good reproducibility and high selectivity,
      demonstrating its feasibility for the analytical purpose. Lastly, this new sensor
      was used for the determination of d-penicillamine and tryptophan in real samples.

PMID- 28762330
TI  - Optimization of the Supercritical Carbon Dioxide Separation of Bergapten from
      Bergamot Essential Oil.
AB  - The possibility of following traditional cold-press extraction with the post
      process continuous separation of bergapten from bergamot essential oil was
      investigated. A fractionation tower was used in an experiment in which cold
      pressed bergamot oil was extracted in a continuous countercurrent process by
      supercritical carbon dioxide under different conditions. Bergapten is fairly
      soluble in CO2 in its supercritical phase, in particular at a density of 277.90
      kg?m-3, corresponding to a pressure of 8 MPa and temperature of 40 degrees C.
      Under these conditions, an extract with 0.198% bergapten was obtained, a figure
      slightly below the percentage of bergapten contained in cold-pressed oil (0.21%).
      However, at densities below 200 kg?m-3, the amount of bergapten in the extracted
      oil was negligible. Of all tested conditions for separation, the best was found
      to be at a pressure of 8 MPa and temperature of 70 degrees C, conditions under
      which bergapten was not detected. The results of the experiment showed that
      bergapten, and the non-volatile fraction in general, was extracted only in small
      quantities and was not extracted at all with at a CO2 pressure of 8 MPa.

PMID- 28762331
TI  - Quantitative Determination of Synthesized Genotoxic Impurities in Nifuroxazide
      Capsules by Validated Chromatographic Methods.
AB  - Two accurate, selective, and precise chromatographic methods, namely TLC
      densitometric and reversed-phase (RP)-HPLC, were developed and validated for the
      simultaneous determination of nifuroxazide (NIF) and its four synthesized
      impurities, which are also reported to be its related substances in the range of
      10-100 MUg/band and 10-100 MUg/mL for NIF in the TLC and RP-HPLC methods,
      respectively. The developed TLC-densitometric method depended on the separation
      and quantitation of the studied components on silica gel 60 F254 TLC plates.
      Ethyl acetate-acetone-methanol-ammonia (85 + 25 + 5 + 0.5, v/v/v/v) was used as
      the developing system, and the separated bands were UV-scanned at 230 nm. On the
      other hand, the developed RP-HPLC method depended on chromatographic separation
      using a C8 column at 25 degrees C and an aqueous solution of 0.1% sodium lauryl
      sulfate-acetonitrile as the mobile phase delivered according to the gradient
      elution program. Factors affecting the developed methods were studied and
      optimized. Also, method validation was carried out according to International
      Conference on Harmonization guidelines. The proposed methods were successfully
      applied for the determination of the studied drug in its bulk powder and in its
      pharmaceutical formulation. The developed methods showed no significant
      difference when compared with the reported RP-HPLC one. Their advantage is being
      the first stability-indicating methods for NIF and its genotoxic impurities.

PMID- 28762332
TI  - Long Noncoding RNA NEAT1 Promotes Proliferation and Invasion via Targeting miR
      181a-5p in Non-Small Cell Lung Cancer.
AB  - Long noncoding RNAs (lncRNAs) have been implicated in various biological
      processes and pathological conditions, including tumorigenesis. However, the
      exact roles of NEAT1 and its underlying mechanisms in non-small cell lung cancer
      (NSCLC) remain largely unclear. In the present study, lncRNA NEAT1 was detected
      to be significantly upregulated in NSCLC tissues and closely associated with
      advanced TNM stages, lymph node metastasis, distant metastasis, and poor
      prognosis. Further experiments revealed that lncRNA NEAT1 silencing inhibited
      cell proliferation and invasion in vitro. In addition, mechanistic analysis
      showed that lncRNA NEAT1 upregulated the miR-181a-5p-targeted gene HMGB2 through
      acting as a competitive "sponge" of miR-181a-5p. In conclusion, our study
      suggested that lncRNA NEAT1 plays an oncogenic role in NSCLC progression and
      provides potential mechanisms by which lncRNA NEAT1 contributes to this disease.

PMID- 28762334
TI  - Controlled formation of gold nanostructures on biopolymer films upon
      electromagnetic radiation.
AB  - The localized formation of gold nanostructures with controlled size and shape on
      chitosan films doped with gold precursor upon electromagnetic irradiation of
      various types is demonstrated here. Such controlled formation is achieved by
      tuning the wavelength, the energy and the interaction time of the radiation with
      the composite films. In particular, the use of a single UV nanosecond laser pulse
      results in the formation of gold sub-micron platelets with specific crystal
      structure, while increasing the number of pulses, further precursor reduction and
      photofragmentation induce the formation of gold nanoparticles. Using x-ray
      radiation as an alternative energy source, the reduction of the gold precursor
      and the subsequent formation of particles follow a different pathway.
      Specifically, x-ray-induced photo-reduction triggers the selective formation of
      gold sub-micron platelets with a very well defined {111} crystal phase. In this
      case, the density of crystal platelets increases by increasing the irradiation
      time of the films, while no photofragmentation process is observed. The gold
      structures pre-formed by x-ray radiation can be fragmented by subsequent pulsed
      UV laser irradiation forming nanoparticles with much narrower size distribution
      compared to that obtained via exclusive UV irradiation. Thanks to the perfect
      coupling between the natural polymeric matrix and gold nanostructures, the
      bionanocomposite systems developed could find various applications in biomaterial
      science and in biosensors field.

PMID- 28762335
TI  - Helium ions at the heidelberg ion beam therapy center: comparisons between FLUKA
      Monte Carlo code predictions and dosimetric measurements.
AB  - In the field of particle therapy helium ion beams could offer an alternative for
      radiotherapy treatments, owing to their interesting physical and biological
      properties intermediate between protons and carbon ions. We present in this work
      the comparisons and validations of the Monte Carlo FLUKA code against in-depth
      dosimetric measurements acquired at the Heidelberg Ion Beam Therapy Center (HIT).
      Depth dose distributions in water with and without ripple filter, lateral
      profiles at different depths in water and a spread-out Bragg peak were
      investigated. After experimentally-driven tuning of the less known initial beam
      characteristics in vacuum (beam lateral size and momentum spread) and simulation
      parameters (water ionization potential), comparisons of depth dose distributions
      were performed between simulations and measurements, which showed overall good
      agreement with range differences below 0.1 mm and dose-weighted average dose
      differences below 2.3% throughout the entire energy range. Comparisons of lateral
      dose profiles showed differences in full-width-half-maximum lower than 0.7 mm.
      Measurements of the spread-out Bragg peak indicated differences with simulations
      below 1% in the high dose regions and 3% in all other regions, with a range
      difference less than 0.5 mm. Despite the promising results, some discrepancies
      between simulations and measurements were observed, particularly at high
      energies. These differences were attributed to an underestimation of dose
      contributions from secondary particles at large angles, as seen in a triple
      Gaussian parametrization of the lateral profiles along the depth. However, the
      results allowed us to validate FLUKA simulations against measurements, confirming
      its suitability for 4He ion beam modeling in preparation of clinical
      establishment at HIT. Future activities building on this work will include
      treatment plan comparisons using validated biological models between proton and
      helium ions, either within a Monte Carlo treatment planning engine based on the
      same FLUKA code, or an independent analytical planning system fed with a
      validated database of inputs calculated with FLUKA.

PMID- 28762333
TI  - Risk factors for hemoptysis complicating 17-18 gauge CT-guided transthoracic
      needle core biopsy: multivariate analysis of 249 procedures.
AB  - PURPOSE: We aimed to identify modifiable and nonmodifiable risk factors for
      hemoptysis complicating computed tomography (CT)-guided transthoracic needle
      biopsy. METHODS: All procedures performed in our institution from November 2013
      to May 2015 were reviewed. Hemoptysis was classified as mild if limited to
      hemoptoic sputum and abundant otherwise. Presence of intra-alveolar hemorrhage on
      postbiopsy CT images was also evaluated. Patient- and lesion-related variables
      were considered nonmodifiable, while procedure-related variables were considered
      modifiable. RESULTS: A total of 249 procedures were evaluated. Hemoptysis and
      alveolar hemorrhage occurred in 18% and 58% of procedures, respectively, and were
      abundant or significant in 8% and 17% of procedures, respectively. Concordance
      between the occurrence of significant alveolar hemorrhage (grade >=2) and
      hemoptysis was poor (kappa=0.28; 95% CI [0.16-0.40]). In multivariate analysis,
      female gender (P = 0.008), a longer transpulmonary needle path (P = 0.014), and
      smaller lesion size (P = 0.044) were independent risk factors for hemoptysis.
      Transpulmonary needle-path length was the only risk factor for abundant
      hemoptysis with borderline statistical significance (P = 0.049). CONCLUSION: The
      transpulmonary needle path should be as short as possible to reduce the risk of
      abundant hemoptysis during CT-guided transthoracic needle biopsy.

PMID- 28762336
TI  - Performance of an open-source heart sound segmentation algorithm on eight
      independent databases.
AB  - OBJECTIVE: Heart sound segmentation is a prerequisite step for the automatic
      analysis of heart sound signals, facilitating the subsequent identification and
      classification of pathological events. Recently, hidden Markov model-based
      algorithms have received increased interest due to their robustness in processing
      noisy recordings. In this study we aim to evaluate the performance of the
      recently published logistic regression based hidden semi-Markov model (HSMM)
      heart sound segmentation method, by using a wider variety of independently
      acquired data of varying quality. APPROACH: Firstly, we constructed a systematic
      evaluation scheme based on a new collection of heart sound databases, which we
      assembled for the PhysioNet/CinC Challenge 2016. This collection includes a total
      of more than 120 000 s of heart sounds recorded from 1297 subjects (including
      both healthy subjects and cardiovascular patients) and comprises eight
      independent heart sound databases sourced from multiple independent research
      groups around the world. Then, the HSMM-based segmentation method was evaluated
      using the assembled eight databases. The common evaluation metrics of
      sensitivity, specificity, accuracy, as well as the [Formula: see text] measure
      were used. In addition, the effect of varying the tolerance window for
      determining a correct segmentation was evaluated. MAIN RESULTS: The results
      confirm the high accuracy of the HSMM-based algorithm on a separate test dataset
      comprised of 102 306 heart sounds. An average [Formula: see text] score of 98.5%
      for segmenting S1 and systole intervals and 97.2% for segmenting S2 and diastole
      intervals were observed. The [Formula: see text] score was shown to increases
      with an increases in the tolerance window size, as expected. SIGNIFICANCE: The
      high segmentation accuracy of the HSMM-based algorithm on a large database
      confirmed the algorithm's effectiveness. The described evaluation framework,
      combined with the largest collection of open access heart sound data, provides
      essential resources for evaluators who need to test their algorithms with
      realistic data and share reproducible results.

PMID- 28762337
TI  - Superiorized algorithm for reconstruction of CT images from sparse-view and
      limited-angle polyenergetic data.
AB  - Recent work in CT image reconstruction has seen increasing interest in the use of
      total variation (TV) and related penalties to regularize problems involving
      reconstruction from undersampled or incomplete data. Superiorization is a
      recently proposed heuristic which provides an automatic procedure to
      'superiorize' an iterative image reconstruction algorithm with respect to a
      chosen objective function, such as TV. Under certain conditions, the superiorized
      algorithm is guaranteed to find a solution that is as satisfactory as any found
      by the original algorithm with respect to satisfying the constraints of the
      problem; this solution is also expected to be superior with respect to the chosen
      objective. Most work on superiorization has used reconstruction algorithms which
      assume a linear measurement model, which in the case of CT corresponds to data
      generated from a monoenergetic x-ray beam. Many CT systems generate x-rays from a
      polyenergetic spectrum, however, in which the measured data represent an integral
      of object attenuation over all energies in the spectrum. This inconsistency with
      the linear model produces the well-known beam hardening artifacts, which impair
      analysis of CT images. In this work we superiorize an iterative algorithm for
      reconstruction from polyenergetic data, using both TV and an anisotropic TV (ATV)
      penalty. We apply the superiorized algorithm in numerical phantom experiments
      modeling both sparse-view and limited-angle scenarios. In our experiments, the
      superiorized algorithm successfully finds solutions which are as constraints
      compatible as those found by the original algorithm, with significantly reduced
      TV and ATV values. The superiorized algorithm thus produces images with greatly
      reduced sparse-view and limited angle artifacts, which are also largely free of
      the beam hardening artifacts that would be present if a superiorized version of a
      monoenergetic algorithm were used.

PMID- 28762338
TI  - Selective Dirac voltage engineering of individual graphene field-effect
      transistors for digital inverter and frequency multiplier integrations.
AB  - The ambipolar band structure of graphene presents unique opportunities for novel
      electronic device applications. A cycle of gate voltage sweep in a conventional
      graphene transistor produces a frequency-doubled output current. To increase the
      frequency further, we used various graphene doping control techniques to produce
      Dirac voltage engineered graphene channels. The various surface treatments and
      substrate conditions produced differently doped graphene channels that were
      integrated on a single substrate and multiple Dirac voltages were observed by
      applying a single gate voltage sweep. We applied the Dirac voltage engineering
      techniques to graphene field-effect transistors on a single chip for the
      fabrication of a frequency multiplier and a logic inverter demonstrating analog
      and digital circuit application possibilities.

PMID- 28762339
TI  - Deep learning for single-molecule science.
AB  - Exploring and making predictions based on single-molecule data can be
      challenging, not only due to the sheer size of the datasets, but also because a
      priori knowledge about the signal characteristics is typically limited and poor
      signal-to-noise ratio. For example, hypothesis-driven data exploration, informed
      by an expectation of the signal characteristics, can lead to interpretation bias
      or loss of information. Equally, even when the different data categories are
      known, e.g., the four bases in DNA sequencing, it is often difficult to know how
      to make best use of the available information content. The latest developments in
      machine learning (ML), so-called deep learning (DL) offer interesting, new
      avenues to address such challenges. In some applications, such as speech and
      image recognition, DL has been able to outperform conventional ML strategies and
      even human performance. However, to date DL has not been applied much in single
      molecule science, presumably in part because relatively little is known about the
      'internal workings' of such DL tools within single-molecule science as a field.
      In this Tutorial, we make an attempt to illustrate in a step-by-step guide how
      one of those, a convolutional neural network (CNN), may be used for base calling
      in DNA sequencing applications. We compare it with a SVM as a more conventional
      ML method, and discuss some of the strengths and weaknesses of the approach. In
      particular, a 'deep' neural network has many features of a 'black box', which has
      important implications on how we look at and interpret data.

PMID- 28762341
TI  - Publication ethics and etiquette: The golden commandments!

PMID- 28762340
TI  - High-energy x-ray Talbot-Lau radiography of a human knee.
AB  - We report on a radiographic measurement of an ex vivo human knee using a grating
      based phase-contrast imaging setup and a medical x-ray tube at a tube voltage of
      70 kV. The measurement has been carried out using a Talbot-Lau setup that is
      suitable to achieve a high visibility in the energy regime of medical imaging. In
      a medical reading by an experienced trauma surgeon signatures of
      chondrocalcinosis in the medial meniscus have been identified more evidently
      using the dark-field image in comparison to the conventional attenuation image.
      The analysis has been carried out at various dose levels down to 0.14 mGy
      measured as air kerma, which is a dose comparable to clinically used radiographic
      devices. The diagnosis has been confirmed by a histological analysis of the
      meniscus tissue. In the introduced high-frequency filtered phase-contrast image
      the anterior and posterior horn of the medial meniscus and the posterior cruciate
      ligament have also been visible. Furthermore, atherosclerotic plaque is visible
      in both imaging modalities, attenuation and dark-field, despite the presence of
      overlaying bone. This measurement, for the first time, proves the feasibility of
      Talbot-Lau x-ray imaging at high-energy spectra above 40 kVp and reasonable dose
      levels with regard to spacious and dense objects.

PMID- 28762342
TI  - Assessment of malocclusion severity and orthodontic treatment needs in 12-15-year
      old school children of Namakkal District, Tamil Nadu, using Dental Aesthetic
      Index.
AB  - OBJECTIVES: The present study was aimed to assess the severity of malocclusion
      and orthodontic treatment needs among 12-15-year-old schoolchildren in rural area
      of Namakkal district, Tamil Nadu, India, using the Dental Aesthetic Index (DAI).
      MATERIALS AND METHODS: A cross-sectional study was conducted among a sample of
      1078 schoolchildren (12-15 years of age) who were selected by two-stage cluster
      sampling technique. Severity of malocclusion and orthodontic treatment needs were
      assessed according to the DAI using a specially designed survey pro forma with
      the aid of the WHO's Oral Health Survey: Basic Methods. Based on the distribution
      of data, analysis of variance and unpaired student t-test were used. RESULTS: Out
      of the total of 1078 children examined, 528 (49%) were males and 550 (57%) were
      females. The results indicate that 82.74% of the schoolchildren were found with
      little or no malocclusion requiring no orthodontic treatment. The gender-wise
      distribution of DAI score among children aged 12 years had significant difference
      between males (20.43 +/- 3.67) and females (21.62 +/- 4.335) (P = 0.015) and
      children aged 15 years also showed highly significant difference among gender (P
      = 0.000). CONCLUSION: Malocclusion not only impacts the appearance of the person
      but also affects the self-esteem and psychological well-being. This is the first
      step in understanding the treatment need so that further steps can be taken in
      preventive and interceptive care.

PMID- 28762343
TI  - Assessment of maternal risk factors and its relationship with early childhood
      caries among preschool children in Mangaluru city.
AB  - AIM: The aim of this study is to assess the maternal risk factors and its
      relationship with early childhood caries (ECC) among preschoolchildren in
      Mangaluru city. METHODS: Children aged 3-5 years attending preschool (Anganwadi)
      and their mothers were included in the study. A total of 120 child-mother pairs
      participated in the study. The maternal risk factors were assessed by a pretested
      questionnaire. After obtaining the consent, the mother and their children were
      clinically examined for dental caries using the WHO criteria (1997). Results were
      analyzed using SPSS 18.0. RESULTS: Significant difference was found in mother's
      caries activity, high level of Streptococcus mutans, brushing frequency, diet of
      the mother, and their child's caries experience. CONCLUSION: A relationship
      between maternal risk factors and ECC is a result of a multifactorial and a
      comprehensive model that includes psychological and behavioral aspects. Caries
      prevention strategy should be that every child should receive oral care before
      age of one so that needful children can be instituted with preventive measures
      and their parents can be targeted for educational programs.

PMID- 28762344
TI  - Assessment of fluoride retention in jowar consuming population: A cross-sectional
      study.
AB  - INTRODUCTION: Dental fluorosis is considered as a serious public health problem
      in India. Water is usually the major source of fluoride exposure, but this is not
      the case always as exposure to local factors like diet can be important in some
      situations. Earlier studies have shown that jowar (a millet) consumption
      interacts with fluoride in the body and elevate fluorosis. AIM AND OBJECTIVE: To
      determine the association between jowar consumption and severity of dental
      fluorosis. MATERIALS AND METHODS: Hundred schoolgoing children of 10-14 years old
      was selected by random sampling from Wadloor village. Dental fluorosis was
      measured in children by Thylstrup-Fejerskov index (1988). Twenty-four hours diet
      recall method was used to know the exposure to jowar of the children. A pretested
      questionnaire was given to mother or caretaker to record the jowar consumption.
      Spot urine samples of children were collected in plastic containers (20 ml) and
      brought to the laboratory in icebox. Ion selective electrode method was used to
      measure the fluoride level in urine samples of children. RESULTS: On comparison
      of the quantity of jowar and fluorosis using Pearson Chi-square test, difference
      among variable was found out to be statistically significant (P = 0.013, P <
      0.05). On comparison of quantity jowar consumption and urinary fluoride level
      using Pearson Chi-square test, the difference among variable was found
      statistically significant (P < 0.001). CONCLUSION: Jowar consuming population was
      positively associated with severity of dental fluorosis.

PMID- 28762345
TI  - Assessment of dental caries and periodontal status in institutionalized hearing
      impaired children in Khordha District of Odisha.
AB  - INTRODUCTION: Over 5% of the world's population has disabling hearing loss. The
      oral health of the disabled may be disused for the reason of the disabling
      condition, a challenging disease or the limited access to oral health care.
      OBJECTIVES: The objectives of the study were to assess the prevalence of dental
      caries and periodontal status of institutionalized hearing impaired (HI) children
      in Khordha district of Odisha. MATERIALS AND METHODS: A descriptive cross
      sectional study on the HI children was conducted in Khordha district, Odisha.
      Type III examination procedure was conducted to assess the oral health status of
      the children. Statistical analysis was performed by Chi-square test and Student's
      t-test, and the significance level was fixed at P < 0.05. RESULTS: The final
      population consisted of 540 HI children out of which 262 (48.5%) were male and
      278 (51.5%) were female, 285 (52.8%) children had severe hearing loss and 227
      (42.0%) had profound hearing loss. Bleeding on probing was found in 72 (13.3%)
      female children as compared to 57 (10.6%) male children. While 131 (24.3%) female
      children had calculus, 124 (23.0%) male children had the same condition. Total
      caries prevalence was 19.3%. Statistically highly significant difference was
      found for mean decayed teeth (DT), missing teeth decayed, missing filled teeth
      (FT) (P < 0.001), while for mean FT there was no statistically significant
      difference according to age groups. Statistically highly significant difference
      was found for mean DT, extracted teeth and decayed, extracted, filled teeth (P <
      0.001). CONCLUSION: An improved accessibility to dental services as well as
      dental health education is necessary to ensure the optimum dental health within
      the reach of these less fortunate children.

PMID- 28762346
TI  - Prevalence of traumatic dental injuries among visually impaired children
      attending special schools of Chhattisgarh.
AB  - BACKGROUND: Studies on dental trauma of the normal population have been carried
      out in the past; however, limited data are available on dental trauma of the
      handicapped population, especially visually impaired children in Chhattisgarh,
      India. AIM: The aim of this study is to determine the prevalence of traumatic
      dental injuries (TDIs) in visually impaired children in relation to age, cause,
      and place of injury. MATERIALS AND METHODS: Epidemiological study was carried out
      among 400 children from various special schools of visually impaired children of
      Chhattisgarh followed by school dental checkup camps. All the children completed
      a questionnaire related history of trauma, cause, and place. The prevalence of
      TDIs in each special child was recorded based on the Epidemiological
      classification of TDIs by the WHO and was modified by Andreasen et al. (2007).
      STATISTICAL ANALYSIS: Statistical analysis was done using SPSS version 17. The
      level of significance was fixed at P <= 0.05. Association between categorical
      variables was done using Chi-square test. RESULTS: The results showed that out of
      400 children, 39% suffered from TDIs. Permanent maxillary central incisors were
      most commonly injured teeth with injuries involving enamel (53%) being most
      frequently observed. Increased overjet and inadequate lip coverage were
      significantly associated with the occurrence of trauma. CONCLUSION: As blind
      children are at the risk of multiple TDI, it is necessary to create awareness,
      health education, and periodic screening for appropriate management.

PMID- 28762347
TI  - Barriers to dental care for children with special needs: General dentists'
      perception in Kerala, India.
AB  - INTRODUCTION: Special children are among the underserved dental patient groups
      around the globe. Oral health care for disabled children remain an unmet
      challenge. One out of two persons with a significant disability cannot find a
      professional resource to provide appropriate dental care. Identification of
      barriers can be the first step in addressing the deficiencies in dental care for
      such patients. AIM: To investigate the perception of dental practitioners in
      Kerala, India regarding the hurdles faced by them in providing dental care to
      Special Needs Children including the challenges faced by them. MATERIALS AND
      METHOD: 149 dental professionals were interviewed through a questionnaire for
      their perceived barriers to provide oral health care for children with special
      needs. STATISTICAL ANALYSIS: The data was obtained and Chi-square test, Pearson
      correlation coefficient and logistic regression model were assessed using the
      SPSS version 20.0. All analyses were performed using a level of 0.05 for
      statistical significance. RESULTS: Greatest barriers as perceived by the
      practitioners were their level of training and lack of motivation of caretakers.
      Significant association was found between experience of the dentist with the
      frequency with which they reported seeing children with special needs
      (pConclusion: Findings from this study provide a valid picture of barriers to
      access for children with special needs within general dental private practice
      system. Recommendations for amendment of undergraduate dental curriculum is made
      in order to equip future graduates to deal with this group of children better.

PMID- 28762348
TI  - Behavioral changes during dental appointments in children having tooth
      extractions.
AB  - BACKGROUND: Tooth extractions are associated with anxiety-related situations that
      can cause behavioral problems in pediatric dental clinics. AIM: We aimed to
      describe the behavior of children during tooth extraction appointments, compare
      it to their behavior in preceding and subsequent dental appointments, and assess
      the behavioral differences according to gender, age, type of dentition, and
      reason for extraction. SETTINGS AND DESIGN: This was a retrospective study based
      on information obtained from records of children between 6 and 13 years of age
      who were cared for at the Dentistry School in Pelotas, Brazil. MATERIALS AND
      METHODS: Child behavior was assessed during the dental appointment that preceded
      the tooth extraction, during the tooth extraction appointment, and in the
      subsequent dental appointment using the Venham Behavior Rating Scale. STATISTICAL
      ANALYSIS: Results were analyzed using the Pearson Chi-square and McNemar tests.
      RESULTS: Eighty-nine children were included. Cooperative behavior prevailed in
      all the dental appointments. The prevalence of "mild/intense protest" was higher
      in the tooth extraction appointments than in the previous or subsequent dental
      appointments (P < 0.001). No significant differences in behavior were detected
      between the type of dentition (primary or permanent teeth), reason for extraction
      or gender. CONCLUSION: In this sample of children treated at a dental school, the
      occurrence of uncooperative behavior was higher during the tooth extraction
      appointments than in the preceding and subsequent dental appointments.

PMID- 28762349
TI  - A comparative evaluation of the remineralization potential of three commercially
      available remineralizing agents on white spot lesions in primary teeth: An in
      vitro study.
AB  - BACKGROUND: The focus in caries management has shifted to early detection of
      caries lesions and targeted noninvasive management of incipient lesions using
      novel remineralizing agents. AIM: This study aimed to compare and evaluate the
      remineralization potential of commercially available agents containing nano
      hydroxyapatite (nano-HA), casein phosphopeptide-amorphous calcium phosphate
      fluoride (CPP-ACPF), and Tricalcium phosphate (TCP) on artificially induced white
      spot lesions in primary teeth. SETTINGS AND DESIGN: This is an in vitro double
      blind randomized study. MATERIALS AND METHODS: Forty extracted or exfoliated
      primary teeth were selected and randomized as follows: Group I: FTCP, Group II:
      fluoridated dentifrice, Group III: CPP-ACPF, and Group IV: Nano-HA. DIAGNOdent
      readings and scanning electron microscope (SEM) energy dispersive X-ray (EDX)
      analysis were carried out at baseline. The samples were subjected to the test
      agents after inducing white spot lesions. The readings were repeated
      postdemineralization and postremineralization. STATISTICAL ANALYSIS: The data
      were analyzed using IBM SPSS version 20 software with one-way ANOVA, post hoc
      Tukey's HSD, and paired t-test. RESULTS: SEM evaluation showed favorable surface
      changes in all the four study groups after remineralization therapy. Intragroup
      comparison of DIAGNOdent and EDX readings showed a highly significant difference
      between baseline, postdemineralization, and postremineralization values. However,
      the intergroup comparison was statistically nonsignificant. CONCLUSION: All test
      agents were comparable in their remineralization potential.

PMID- 28762350
TI  - Comparative evaluation of microleakage between bulk esthetic materials versus
      resin-modified glass ionomer to restore Class II cavities in primary molars.
AB  - AIM: The aim of the study was to assess the microleakage of one high-viscosity
      conventional glass ionomer cement (GIC) and a bulk-fill composite resin, in
      comparison to a resin-modified GIC in Class II restorations in primary molars.
      MATERIALS AND METHOD: Standardized Class II slot cavity preparations were
      prepared in exfoliating primary molars. Teeth were restored using one of the
      three materials tested (n = 10): SonicFill bulk-fill composite resin (SF), EQUIA
      Fil conventional reinforced GIC (EQF), and Vitremer resin-reinforced GIC (VT).
      The restorations were then subjected to thermocycling procedure (*2000 5 degrees
      C-55 degrees C 10 s/min) and soaked in 1% neutralized fuchsin solution (pH: 7.4)
      for 24 h at 37 degrees C. Teeth were sectioned longitudinally in a mesiodistal
      direction under continuous cooling into three slabs of 1 mm thickness and studied
      under a stereomicroscope for dye penetration. STATISTICAL ANALYSIS: Data were
      evaluated by one-way analysis of variance and the Tukey's multiple comparison
      test employing 95% (alpha = 0.05). RESULTS: EQF and SF showed significantly lower
      microleakage scores and percentage of dye penetration (%RL) when compared to VT
      resin-reinforced GIC (P < 0.001). CONCLUSION: SF and EQF produced the minimum
      microleakage when compared to VT in Class II restorations on primary molars.
      Fewer application procedures and reduction in treatment time in SF and EQF
      systems proved advantageous in pediatric dentistry.

PMID- 28762351
TI  - Volumetric evaluation of various obturation techniques in primary teeth using
      cone beam computed tomography - An in vitro study.
AB  - AIM: The aim of this study was to compare and evaluate the efficiency of five
      different obturation methods in delivering the filling material into the canals
      of primary teeth using cone beam computerized tomography (CBCT) scan. METHOD: A
      total of fifty prepared canals of primary teeth which further divided into five
      groups with ten canals in each group were obturated with zinc oxide-eugenol
      cement using five different obturation methods such as endodontic plugger,
      lentulo spiral (handheld), lentulo spiral mounted on slow speed handpiece, local
      anesthetic syringe, and tuberculin syringe. Using CBCT scan, the pre- and post
      obturation volume and the percentage of obturated volume (POV) were calculated
      for each group. The results obtained were statistically analyzed using one-way
      analysis of variance and Tukey's post hoc test. RESULTS: Following CBCT scan, the
      method obturated with lentulo spiral mounted to handpiece showed the highest POV
      value followed by the method of lentulo spiral mounted to handpiece, hand
      plugger, and tuberculin syringe. Local anesthetic syringe gave the least POV (P <
      0.05). CONCLUSION: Lentulo spiral mounted to handpiece showed the best technique
      of obturation using CBCT evaluation among the five groups evaluated in primary
      teeth. However, more studies are highly essential to prove it a boon for
      estimating obturation quality in primary teeth.

PMID- 28762352
TI  - A comparative study to associate the presence of neonatal line in deciduous teeth
      of infants with the occurrence of live birth.
AB  - CONTEXT: The prominent striae of retzius corresponding to the occurrence of live
      birth is known as the neonatal line (NNL). The very presence of this line
      indicates the exposure of the infant to the stressful event of birth. AIMS: The
      study was aimed at locating the NNL in the developing primary teeth of the
      neonate and associating the presence of NNL to the occurrence of live birth.
      MATERIALS AND METHODS: The donated bodies of the neonates were taken, and a
      surgical incision was made along the crest of the alveolar ridge in the maxillary
      anterior region, enabling the careful removal of the tooth germs from within the
      jaw segment. The maxillary central incisor tooth germs were embedded in acrylic
      and viewed under the stereomicroscope, polarized microscope, and scanning
      electron microscope (SEM). STATISTICAL ANALYSIS: This being a pilot observational
      study, no statistical analysis methods were employed. RESULTS: The NNL was best
      visualized under polarized microscopy and was clearly appreciated in the control
      samples and faintly seen in the 10-day-old neonate. No evidence of the line was
      present in the tooth germ of the stillborn child. CONCLUSION: The very presence
      of the NNL indicates that the infant was alive during the stressful process of
      birth. This can be used as substantial evidence in infanticide cases brought
      before the law.

PMID- 28762353
TI  - Effect of three commercially available chewing gums on salivary flow rate and pH
      in caries-active and caries-free children: An in vivo study.
AB  - BACKGROUND AND AIM: Adequate salivary flow is an important requisite in the
      maintenance of oral health. Salivary flow increases in response to both gustatory
      (taste) and mechanical (chewing) stimuli. Hence, the aim of the present study was
      to know the efficacy of commercially available chewing gums (sugar free and
      sugared) on salivary flow rate (SFR) and pH in caries-active and caries-free
      children. MATERIALS AND METHODS: One hundred school children aged between 10 and
      12 years were divided into two groups on the basis of their caries status into
      caries free and caries active. Unstimulated saliva was collected before start of
      the study. Both groups were subjected to three commercially available chewing
      gums (2 sugar free, 1 sugared) on consecutive days, and saliva was collected at
      intervals of 2 min (T2), 10 min (T10), and 30 min (T30). The pH and flow rate of
      saliva samples were measured before and specified time intervals after gum
      chewing. RESULTS: In both the groups, gum chewing increased the SFR,
      significantly at T2, and gradually declined at T30 which was significantly higher
      than baseline values. The pH raised significantly at T2 and gradually declined at
      T30 which was significantly higher than baseline values with sugar-free gums, but
      with sugared gums, the pH raised slightly at T2 and dropped significantly at T30.
      However, no statistically significant differences in pH and flow rate were
      noticed in both the groups. CONCLUSION: Chewing of sugar-free gums in both caries
      active and caries-free children may aid in reducing the incidence of dental
      caries.

PMID- 28762354
TI  - A comparison of various minimally invasive techniques for the removal of dental
      fluorosis stains in children.
AB  - CONTEXT: Dental fluorosis is caused by successive exposure to high concentrations
      of fluoride during tooth development leading to enamel with lower mineral content
      and increased porosity. AIMS: The aim of the study was to evaluate and compare
      the effectiveness of minimally invasive techniques for the removal of dental
      fluorosis stains in children in vivo. DESIGN: Ninety children in the age group of
      10-17 years were selected. MATERIALS AND METHODS: The study sample was equally
      and randomly divided into three groups; Group 1: In-office bleaching with 35%
      hydrogen peroxide (HP) activated by light-emitting diode (LED) bleaching unit
      (35% HP), Group 2: Enamel microabrasion (EM) followed by in-office bleaching with
      44% carbamide peroxide gel (EM), Group 3: In-office bleaching with 5% sodium
      hypochlorite (5% NaOCl). Statistical analysis was done using one-way ANOVA test.
      RESULTS: Bleaching with 35% HP activated by LED bleaching unit and EM followed by
      bleaching with 44% carbamide peroxide were equally effective for the removal of
      dental fluorosis stains in children in vivo. However, bleaching with 5% NaOCl
      could not completely remove moderate to severe stains. It was effective in
      removing only mild stains. Bleaching and microabrasion procedures caused slight
      decrease in tooth sensitivity readings by electric pulp vitality tester which
      continued to increase over time. However, none of the patients reported
      sensitivity in their teeth at any point of time. Patients were highly satisfied
      with the treatment outcome postoperatively but reported slight relapse of color
      in the three groups. CONCLUSIONS: Bleaching and microabrasion techniques can
      consider as an interesting alternatives to conventional operative treatment
      options.

PMID- 28762355
TI  - Bismuth subnitrate iodoform parafin paste used in the management of inflammatory
      follicular cyst - Report of two cases.
AB  - Dentigerous cyst or follicular cyst is a type of odontogenic cyst which encloses
      the crown of an unerupted tooth and is attached to the amelocemental junction and
      is the second most common odontogenic cyst contributing about 16.6% to 21.3% of
      all odontogenic cysts. Occurrence of Dentigerous cysts according to Shear is
      usually in 3rd and 4th decade in contrast to this finding Shibata et al showed
      that the age of discovery of the dentigerous cyst was generally 9-11 years. The
      treatment indicated for dentigerous cysts are surgical enucleation of the cyst,
      along with removal of the involved tooth; or the use of a marsupialization
      technique, which removes the cyst while preserving the developing tooth. The
      present case report describes the management of dentigerous cysts in children
      with the use of Bismuth Subnitrate Iodoform Paste.

PMID- 28762357
TI  - A novel approach for prosthodontic management of patient with cleft of palate.
AB  - Nutrition is important in every stage of child development. A child born with
      cleft lip and palate may experience difficulties while feeding due to the lack of
      seal of the oral cavity due to incomplete facial and palatal structures.
      Difficulty in feeding leads to inadequate nutrition and affects the health.
      Children with cleft lip and palate need certain modifications to thrive and grow.
      Feeding difficulties should be assessed and intervened as early as possible, as
      they are an important aspect of multidisciplinary team approach in management and
      may have an impact on long-term outcome. This case report presents fabrication of
      feeding appliance in 6-month-old infant with cleft palate with ethylene vinyl
      acetate.

PMID- 28762356
TI  - Antrochoanal polyp arising from benign pseudocyst of maxillary antrum.
AB  - Antrochoanal polyps (ACPs) are benign lesions that arise from the mucosa of the
      maxillary antrum, grow into the maxillary sinus, and reach the choana with nasal
      obstruction being their main symptom. Most of these lesions are small and
      clinically silent and found as incidental finding, but large cysts which occupy
      the entire antrum have also been reported in literature. Nasal endoscopy and
      computer tomography (CT) are the golden standard in the diagnosis of ACPs, and
      enucleation by Caldwell-Luc approach is the recommended treatment for larger
      antral cysts. This article is a report of a 9-year-old male patient diagnosed
      with ACP arising from a benign cyst of maxillary antrum with characteristic
      clinical, CT, and histopathological features along with brief review of
      literature.

PMID- 28762358
TI  - Obituarty.

PMID- 28762359
TI  - Factors associated with antenatal care services utilisation patterns amongst
      reproductive age women in Benin Republic: An analysis of 2011/2012 benin
      republic's demographic and health survey data.
AB  - BACKGROUND: High maternal and neonatal mortality persist in Benin Republic
      despite recent improvements. Numerous women and newborns continue to suffer
      preventable deaths. Although factors associated with the attendance of at least
      one antenatal care (ANC) visit are well documented, there is little evidence on
      factors related to compliance with World Health Organization (WHO) recommended
      four ANC visits. The present study determined the extent to which reproductive
      age mothers received the ANC check-ups at a health facility focussing on the WHO
      recommended regimen. METHODS: We examined factors related to ANC services
      utilisation patterns amongst 8701 women recruited in the 2011/2012 Benin
      Demographic and Health Survey data using multinomial logistic regression.
      RESULTS: The percentage of mothers with full ANC attendance was 59.56%, 27.61%
      received less than 4 visits and 12.84% had never attended ANC services. Results
      showed that out of 13 variables assessed, only the place of residence was not
      associated with ANC seeking. Amongst significant variables, household wealth
      index, female education and desire for pregnancy were the most important factors
      related to ANC services seeking, especially for the achievement of WHO
      recommended four ANC visits. The relative risk ratio of ANC attendance, for the
      achievement of WHO recommended four ANC regimens was high amongst mothers from
      economically well-off households (adjusted relative risk ratio [aRRR] for richest
      women = 10.6, 95% confidence interval [CI]: 6.16-18.33), educated women (aRRR for
      primary level = 4.34, 95% CI: 3.00-6.27) and those with desired pregnancies (aRRR
      = 3.4, 95% CI: 2.58-4.48). CONCLUSION: To achieve WHO-recommended minimum four
      ANC visits in Benin Republic, our findings suggest the need to financially
      support the most economically disadvantaged pregnant women and their families
      during pregnancy, advocate for reducing unmet needs for family planning,
      strengthen girls' education, especially by maintaining them in school till
      completion of at least the secondary school.

PMID- 28762360
TI  - Screening for bacterial vaginosis before intrauterine device insertion at a
      family planning clinic in south-west Nigeria.
AB  - AIM: This study determined the prevalence of bacterial vaginosis (BV) among
      clients before insertion of intrauterine device (IUD) and compared the incidence
      of complications between participants who were positive and negative for BV.
      PATIENTS AND METHODS: This was an observational cohort study that was performed
      between May 2014 and September 2014. A total of 360 women were recruited and
      followed up for 1 month. High vaginal swabs were obtained from each participant
      pre-insertion of the IUD and 1 month post-insertion. BV was diagnosed using
      Nugent's scoring. Data were collected, collated and analysed using frequency
      distributions and Chi-square test as appropriate. The level of statistical
      significance was P< 0.05. RESULTS: The prevalence of BV was 33.3%. The
      complication rate was 23.9% in which 30.5% complication rate was seen among
      participants positive for BV and 22.5% among participants negative for BV (P =
      0.192). This was done with respect to four primary clinical outcomes. The
      incidence of BV one month after IUD insertion was 11.5%. CONCLUSION: The
      prevalence of BV was within the range reported in other populations. The
      complication rate appeared high; however, the differences in proportion between
      women positive and negative for BV were not statistically significant.

PMID- 28762361
TI  - Prevalence of chronic kidney disease and its risk factors among adults in a semi
      urban community of South-East Nigeria.
AB  - BACKGROUND: Chronic kidney disease (CKD) is an increasingly prevalent problem
      worldwide. Treatment of end-stage kidney disease is beyond the reach of an
      average Nigerian. The prevention and early detection are imperative to reducing
      its burden. AIM: The aim of this study was to determine the prevalence of CKD and
      some of its risk factors among adults in a representative semi-urban Nigerian
      population. SUBJECTS AND METHODS: A cross-sectional study involving 400 randomly
      selected adults. Participants were assessed using the WHO stepwise approach.
      Urinary protein-creatinine ratio (PCR) and estimated glomerular filtration rate
      (GFR) from serum creatinine, among other parameters, were analysed. A PCR >=200
      mg/g was regarded as significant proteinuria while GFR <60 ml/min/1.73 m2 was
      regarded as reduced GFR. Participants with abnormal PCR and/or reduced GFR were
      re-evaluated after 3 months to document persistence of these abnormalities. CKD
      was defined as persistent significant proteinuria and/or reduced GFR for more
      than 3 months. RESULTS: Data were complete for 328 participants. Persistent
      significant proteinuria was found in 5.8% while persistently reduced GFR was
      obtained in 4.6% of participants. Overall, the prevalence of CKD was 7.8%. The
      prevalence of some established CKD risk factors was old age, 36.3%; hypertension,
      36.9%; diabetes mellitus, 7.9%; and family history of kidney disease, 6.4%. The
      predictors of CKD included old age (adjusted odds ratio = 3.2; confidence
      interval: 1.10-8.92; P= 0.02), hypertension: 3.5 (1.93-11.90; P= 0.001), family
      history of kidney disease; 4.5 (3.91-10.23; P= 0.01), generalised obesity 1.3
      (1.20-6.21; P= 0.001) and central obesity 3.8 (1.13-12.68; P= 0.003). CONCLUSION:
      The prevalence of CKD and some of its risk factors were high. Effective control
      of the modifiable risk factors identified will assist in reducing the burden of
      CKD.

PMID- 28762362
TI  - Prevalence and pattern of potential drug-drug interactions among chronic kidney
      disease patients in south-western Nigeria.
AB  - BACKGROUND: Management of chronic kidney disease (CKD) patients often requires
      the use of multiple drugs due to a high number of cardiovascular risk factors and
      complications associated with the disease. Multiple drugs predispose to potential
      drug-drug interactions (DDIs) which may be associated with increased morbidity,
      mortality, length of hospital stay and health-care cost. OBJECTIVES: This study
      determined the prevalence and pattern of potential DDIs among CKD patients
      attending Kidney Care Centre, in Ondo City, Nigeria. METHODOLOGY: It was an 18
      month retrospective study that involved the reviewed CKD patients' records. The
      Lexi-Interact database was used to evaluate patients' medications for potential
      DDIs. RESULTS: One hundred and twenty-three (123) CKD patients, made up of 82
      (66.67%) males and 41 (33.33%) females were studied. The mean age of the CKD
      patients was 53.81 +/- 16.03 years. The most common comorbid conditions were
      hypertension in 103 (83.74%) and diabetes mellitus in 39 (31.71%). A total of
      1237 prescriptions were made and the mean number of prescribed medications per
      patient was 10.06 +/- 3.97. A total number of 1851 potential DDIs were observed
      among 118 patients. The prevalence of potential DDIs was 95.9% while the mean
      DDIs per prescription was 1.27. Among the potential DDIs observed, the severity
      was mild in 639 (34.5%), moderate in 1160 (62.7%), major in 51 (2.8%) and only 1
      (0.1%) was of avoid drug combination. The most frequent DDI was between calcium
      carbonate and oral ferrous sulphate. CONCLUSION: The prevalence of potential DDIs
      is high among CKD patients. About 63% of these interactions have moderate
      severity. Clinicians and pharmacists should utilise available DDI software to
      avoid harmful DDIs in CKD patients.

PMID- 28762363
TI  - Routine chest radiograph in pre-employment medical examination for healthcare
      workers: Time for a review of the protocol.
AB  - BACKGROUND: Pre-employment medical examination (PEME) sought to evaluate the
      ability of workers to work without risk to their own or others' health and
      safety. This is important especially in a hospital environment where the patients
      may be at risk in case of employees harbouring infectious lung conditions or as a
      result of occupational exposure. Although not all healthcare workers are at risk
      or pose risk, they are expected to undergo chest X-ray (CXR) as part of PEME.
      AIMS: The aim of this study is to determine the number of prospective employees
      with abnormal findings on routine CXR, describe their characteristics and
      reassess the value of CXR in PEME. SETTINGS AND DESIGN: This was a retrospective
      study of all the staffs employed into the Olabisi Onabanjo University Teaching
      Hospital, Sagamu, Nigeria, from January 2004 to December 2013. SUBJECTS AND
      METHODS: Of the 633 personnel employed during this period, medical records of 416
      staffs were available for analysis. Data extracted included age, gender, and CXR
      report. Descriptive statistics was used for analysis and presentation. RESULTS:
      The mean age of the prospective employees was 26.6 years +/- 5 with a range of 20
      49 years. Three hundred and ninety-six (95.2%) employees had normal CXR report
      while 20 (4.8%) had abnormal CXR. The only abnormality reported was cardiomegaly
      which was found in 66% of those aged >=41 years. Cardiomegaly was significantly
      associated with increasing age (P = 0.003). CONCLUSIONS: Routine CXR as part of
      PEME for prospective employees into this healthcare institution is no longer
      necessary. It is suggested that its routine use should be limited to older job
      seekers.

PMID- 28762364
TI  - Brain and spine imaging artefacts on low-field magnetic resonance imaging:
      Spectrum of findings in a Nigerian Tertiary Hospital.
AB  - BACKGROUND: Low-field (LF) magnetic resonance imaging (MRI) is a technology that
      is widely used in resource-limited settings for clinical imaging. The images
      produced, even though of low resolution with noise and artefacts, provide
      valuable information and guidance for patient assessment and treatment. This
      study shows a spectrum of MRI artefacts that affect image quality during routine
      clinical neuroradiology practice using LF MRI in a Nigerian hospital and suggests
      ways to avoid them. MATERIALS AND METHODS: We retrospectively reviewed brain and
      spine MRI studies performed on a 0.36T MagSense 360 (Mindray, China) open MRI at
      our hospital over a 2-year period to identify image artefacts. About 90% of MRI
      studies performed at our facility during the study period were neuroimaging. The
      pattern and distribution of artefacts that featured during imaging were described
      and illustrative cases demonstrated highlighting their causes and ways to avoid
      or limit them. RESULTS: Of 936 brain and spine cases evaluated, 506 (54.1%) had
      artefacts with 369 (72.9%) seen in the brain. Truncation/Gibbs (37.6%) and motion
      (20.6%) were the most common artefacts in the series, seen most commonly in T2
      weighted images. There was no significant difference in the proportion of
      artefacts between adults and children (P = 0.736). CONCLUSION: Artefacts are
      relatively common in neuroimaging with LF MRI and may potentially degrade image
      quality and interfere with accurate radiological reporting and diagnosis.
      Improving the recognition of LF MRI artefacts may assist imaging practitioners to
      avoid or limit their effect on image quality and interpretation.

PMID- 28762365
TI  - Reliability and validity of the Yoruba version of the Oswestry disability index.
AB  - CONTEXT: Low back pain (LBP) is a major cause of disability, and the Oswestry
      Disability Index (ODI) is a validated assessment tool for evaluating disability
      in LBP patients. Cross-cultural adaptation of the ODI is important because not
      all populations are proficient in English. The Yoruba language is an indigenous
      language spoken by 40 million people in the Western part of Nigeria and some
      countries in West Africa and Latin America. Currently, no validated Yoruba
      version of ODI is available. AIMS: The aim of the study was to translate,
      culturally adapt and validate the ODI in Yoruba language for participants with
      LBP. SUBJECTS AND METHODS: The ODI was translated into Yoruba, and this
      translated version was analysed in terms of semantics and linguistics. Then, the
      Yoruba version was translated back into English and both versions administered to
      160 participants with LBP. The internal consistency using Cronbach's alpha
      coefficient, criterion validity and test-retest reliability were assessed using
      Spearman's rank correlation with significance set at P< 0.05. The inter-rater
      reliability was evaluated by two different observers and the intra-rater
      reliability was determined by the same observer, a week apart. RESULTS: The
      internal consistency of the Yoruba ODI with Cronbach's alpha was 0.97, the
      intrarater reliability yielded an intraclass correlation coefficient of 0.93 and
      criterion validity assessed using Spearman's rank correlation was r = 0.92 for
      highest score and 0.63 for lowest score. CONCLUSION: The Yoruba ODI is a reliable
      and valid tool for assessing functional disability in LBP patients.

PMID- 28762366
TI  - Prevalence and factors associated with exercise-induced bronchospasm among rural
      school children in Ilesa, Nigeria.
AB  - BACKGROUND: Exercise-induced bronchospasm (EIB) assessed using changes in peak
      expiratory flow rates (PEFRs) to free range exercise is a relatively cheap way of
      screening for asthma in resource-poor centres where children with asthma are
      often undiagnosed and poorly managed. This study sets out to determine the
      prevalence and factors associated with EIB among rural schoolchildren in Ilesa,
      Nigeria. SUBJECTS AND METHODS: Children aged 8-16 years from two middle schools
      in rural Ilesa were selected by multistage sampling. Their sociodemographic
      characteristics and personal/family history of asthma and allergies were
      obtained. The children had their PEFR measured before, 5, 10 and 15 min after 6-8
      min of free running exercise to achieve 80% of their maximal pulse rate. EIB was
      defined as change in PEFR expressed as a percentage of the pre-exercise value
      >=15%. The prevalence and factors associated with EIB were determined. RESULTS:
      The mean (standard deviation) age of the 250 study participants was 12.5 (1.5)
      years (M: F 0.9:1) None of the children had previously been diagnosed with
      asthma. The prevalence of EIB was 9.2%, 6.4% and 4.0% at 5, 10 and 15 min post
      exercise, respectively. Household poultry birds, personal history of allergies,
      wheeze in the past 12 months and family history of asthma were associated with
      EIB (P < 0.05); only wheezing in the past 12 months independently predicted EIB
      (odds ratio = 6.343; 95% confidence interval = 2.040-8.798; P= 0.020).
      CONCLUSION: The prevalence of EIB among rural schoolchildren in Ilesa was 9.2%.
      EIB was associated with the history of allergies and wheeze and presence of
      household poultry birds. We recommend routine screening of these children for
      early diagnosis and good asthma symptom control.

PMID- 28762367
TI  - Socioeconomic status of parents and the occurrence of pelvic inflammatory disease
      among undergraduates attending Irrua Specialist Teaching Hospital, Irrua, Edo
      State, Nigeria.
AB  - BACKGROUND: Pelvic inflammatory disease (PID) is a major cause of gynaecological
      morbidity globally. Complications from PID include infertility, ectopic pregnancy
      and chronic pelvic pain. Low socioeconomic status (SES) is a risk factor for the
      occurrence of PID. OBJECTIVE: The aim of this study was to determine the
      association between SES of parents and the occurrence of PID among undergraduates
      attending Irrua Specialist Teaching Hospital, Irrua. METHODOLOGY: The study was a
      hospital-based, descriptive cross-sectional study. Three hundred and sixty female
      undergraduates attending the hospital were consecutively recruited and clinically
      assessed for the presence of PID using the WHO and CDC MMWR 2010 criteria for the
      clinical assessment of PID. Their SES was determined by Oyedeji social class
      categorisation. Data were analysed using Epi Info 3.5.4. Descriptive statistics
      were used to summarise the data, and Chi-square was used to test for association.
      RESULTS: There was a significant association between SES of parents and multiple
      sex partners (P < 0.02), previous sexually transmitted infection (STI) (P =
      0.05), unprotected sex (P < 0.001), history of induced abortion (P < 0.001) and
      surgical termination of pregnancy (P < 0.01). There was also association between
      occurrence of PID among respondents and multiple sexual partners (P < 0.001),
      previous history of STI (P = 0.02), non-persistent use of condom (P < 0.001),
      history of induced abortion (P < 0.01) and surgical termination of pregnancy (P <
      0.01). There was however no significant association between SES of parents and
      occurrence of PID (P = 0.14) though PID was highest among respondents from low
      SES. CONCLUSION: Occurrence of PID among undergraduates was not associated with
      their SES. However, identified risk factors for PID among study population such
      as multiple sex partners, previous STI, unprotected sex and history of induced
      abortion were associated with the SES.

PMID- 28762368
TI  - Antibiotic susceptibility profiles of non-fermenting gram-negative Bacilli at a
      Tertiary Care Hospital in Patiala, India.
AB  - BACKGROUND: Non-fermenting Gram-negative bacilli (NFGNB) have emerged as a major
      cause of healthcare-associated infections and are innately resistant to many
      antibiotics. AIM: The aim of this study was to determine the prevalence of NFGNB
      isolated from various clinical specimens and evaluate their antimicrobial
      susceptibility profiles. MATERIALS AND METHODS: This retrospective study was done
      at our Department of Microbiology from December 2015 to December 2016. NFGNB were
      isolated from a variety of clinical specimens, plated on blood agar and MacConkey
      agar and incubated at 37 degrees C for 18-24 h under aerobic conditions.
      Appropriate biochemical tests were done to identify the organisms isolated.
      Antibiotic susceptibility test was performed using the modified Kirby-Bauer disc
      diffusion method using commercially available discs on Mueller-Hinton agar. Data
      was analyzed using SPSS IBM version 20. RESULTS: Out of 19065 clinical samples,
      cultures were positive in 1854 samples. Out of 1854 culture-positive samples, 216
      (11.6%) yielded NFGNB. Pseudomonas aeruginosa was the most common NFGNB, isolated
      in 190/216 (87.96%) samples, followed by Acinetobacter baumannii (17/216, 7.87%).
      Overall, most of the NFGNB isolates were susceptible to polymyxin B (88.4%),
      imipenem (82.9%) and cefoperazone + sulbactam (50.9%), and a total of 11 (64.71%)
      multidrug-resistant A. baumannii (MDRAB) strains were isolated in the study.
      CONCLUSION: Our study showed a significantly high prevalence of NFGNB. Isolation
      of multidrug-resistant P. aeruginosa and MDRAB in the present study raises the
      concern of rapidly emerging antibiotic resistance in this group of bacteria in
      our region.

PMID- 28762369
TI  - Variable presentation of retrocaval ureter: Report of four cases and review of
      literature.
AB  - Retrocaval ureter is a rare anomaly in which the ureter passes behind the
      inferior vena cava due to abnormal embryogenesis. Very few cases have been
      reported from Africa. Although the anomaly is congenital, patients become
      symptomatic in the third or fourth decade of life. We reviewed the records of
      four patients with the diagnosis of retrocaval ureter and managed in our centre
      between January 2010 and December 2016. Three patients presented with recurrent
      colicky right flank pain while one was asymptomatic. Two patients each had Type I
      and Type II retrocaval ureters, respectively. Surgical repairs were achieved in
      the three symptomatic cases and recovery was uneventful. Retrocaval ureter,
      though congenital, manifests in young adults and it may be symptomatic. Pre
      operative diagnosis may be difficult when the lesion is high and mimics
      pelviureteric junction obstruction. Thus, a high index of suspicion is required
      for pre-operative diagnosis. Under-reporting and asymptomatic cases may account
      for the low incidence.

PMID- 28762370
TI  - Impact of CYP2D6 polymorphisms on endoxifen concentrations and breast cancer
      outcomes.
AB  - We investigated the impact of germline CYP2D6 genotyping done using the non-tumor
      specimen on endoxifen concentrations and/or clinical outcomes in breast cancer
      (BC) patients treated with tamoxifen in published studies. We evaluated published
      data from 13 001 patients in 29 studies. Mean+/-s.d. endoxifen concentrations
      were significantly lower in poor metabolizers (PM) versus extensive metabolizers
      (EM) (8.8+/-7.2 versus 22.3+/-11.8 ng ml-1; P<0.05). The PM status did not
      influence clinical outcomes in majority of the studies. However, only one study
      followed the Gaedigk activity scoring for phenotypic assignments, which predicted
      recurrence-free survival in CYP2D6 poor metabolizers. In two independent studies
      with 1676 patients, low endoxifen concentrations predicted poor BC-free survival.
      From our review of published data we found that standardization of CYP2D6
      genotype-phenotype classification is needed in order to ensure effective
      evaluation of associations between CYP2D6 polymorphisms and endoxifen
      concentrations and BC outcomes. Universal implementation of this standardization
      classification system should be a priority among researchers and laboratories.
      Furthermore, additional clinical research is warranted to determine whether
      patients with CYP2D6 PM phenotypes or low endoxifen levels will have better
      clinical outcomes with increased tamoxifen dosing compared to standard dosing.

PMID- 28762372
TI  - Corrigendum: Controlling hybrid nonlinearities in transparent conducting oxides
      via two-colour excitation.
AB  - This corrects the article DOI: 10.1038/ncomms15829.

PMID- 28762371
TI  - Imatinib-induced ophthalmological side-effects in GIST patients are associated
      with the variations of EGFR, SLC22A1, SLC22A5 and ABCB1.
AB  - Imatinib-induced ophthalmological side-effects, including conjunctiva hemorrhage
      and periorbital oedema, although very common and still remain relatively little
      understood. The present study investigated the effects of genetic polymorphisms
      of drug targets and membrane transporters on these side effects. We found that
      the minor allele of EGFR rs10258429 and SLC22A1 rs683369 were significant risk
      determinants of conjunctival hemorrhage with OR of 7.061 (95%CI=1.791-27.837,
      P=0.005 for EGFR rs10258429 CT+TT vs CC), and 4.809 (95%CI=1.267-18.431, P=0.021
      for SLC22A1 rs683369 GG+CG vs CC). The minor allele of SLC22A5 rs274558 and ABCB1
      rs2235040 were protective factors to periorbital oedema with OR of 0.313
      (95%CI=0.149-0.656, P=0.002 for SLC22A5 rs274558 AA+AG vs GG), and 0.253
      (95%CI=0.079-0.805, P=0.020 for ABCB1 rs2235040 CT vs CC). These results
      indicated that variants in EGFR, SLC22A1, SLC22A5 and ABCB1 influenced the
      incidence of Imatinib-induced ophthalmological toxicities, and polymorphism
      analyses in associated genes might be beneficial to optimize Imatinib treatment.

PMID- 28762373
TI  - Changes in prostate cancer detection rate of MRI-TRUS fusion vs systematic biopsy
      over time: evidence of a learning curve.
AB  - BACKGROUND: To determine the effect of urologist and radiologist learning curves
      and changes in MRI-TRUS fusion platform during 9 years of NCI's experience with
      multiparametric magnetic resonance imaging (mpMRI)/TRUS fusion biopsy. METHODS: A
      prospectively maintained database of patients undergoing mpMRI followed by fusion
      biopsy (Fbx) and systematic biopsy (Sbx) from 2007 to 2016 was reviewed. The
      patients were stratified based on the timing of first biopsy. Cohort 1 (7/2007
      12/2010) accounted for learning curve. Cohort 2 (1/2011-5/2013) and cohort 3
      (5/2013-4/2016) included patients biopsied prior to and after debut of a new
      software platform, respectively. Clinically significant (CS) disease was defined
      as Gleason 7 (3+4) or higher. McNemar's test compared cancer detection rates
      (CDRs) of Sbx and Fbx between time periods. RESULTS: 1528 patients were included
      in the study with 230, 537 and 761 patients included in three respective cohorts.
      Median age (interquartile range) was 61.0 (+/-9.0), 62.0 (+/-7.3), and 64.0 (+/
      11.0) years in three cohorts, respectively (P<0.001). Fbx and Sbx had comparable
      CS CDR in cohort 1 (24.8 vs 22.2%, P=0.377). Fbx detected significantly more CS
      disease compared to Sbx in the following two periods (cohort 2: 31.5 vs 25.0%,
      P=0.001; cohort 3: 36.4 vs 30.3%, P<0.001) and detected significantly less low
      risk disease in the same period (cohort 2: 14.5 vs 19.6%, P<0.001; cohort 3: 12.6
      vs 16.7%, P<0.001). Even after multivariate adjustment with age, PSA, race,
      clinical stage and MRI suspicion score, Fbx CS cancer detection increased in
      successive cohorts (cohort 2: OR 2.23, P=0.043; cohort 3: OR 2.92, P=0.007).
      CONCLUSIONS: In the past 9 years, there has been significant improvement in the
      accuracy of Fbx. Our results show that after an early learning period, Fbx
      detected higher rates of CS cancer and lower rates of clinically insignificant
      cancer than Sbx. Software advances allowed for even greater detection of CS
      disease.

PMID- 28762374
TI  - Molecular alterations in prostate cancer and association with MRI features.
AB  - BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has been
      increasingly used for prostate cancer (PCa). Recent studies identified distinct
      molecular subclasses of PCa with recurrent genomic alterations. However, the
      associations between molecular alterations in PCa and characteristics on mpMRI
      are unknown. Therefore, the objective of this study was to investigate recurrent
      molecular alterations in PCa and their associations with mpMRI features. METHODS:
      Sixty-two PCa nodules >0.5 cm had a preoperative mpMRI. Nodules were evaluated
      for ERG rearrangement, PTEN deletion, SPINK1 overexpression, SPOP mutation and
      CHD1 deletion. Each PCa focus was matched to the corresponding location on mpMRI.
      Lesions were scored by single observer according to the PI-RADSv2 scale. RESULTS:
      Of the 62 nodules, 22 (35.5%) were ERG positive, 6 (9.7%) had SPINK1
      overexpression, 6 (9.7%) had SPOP mutations, 4 (6.5%) had CHD1 deletions and 1
      (1.6%) had PTEN deletion. All of the nodules with CHD1 deletions were not visible
      on mpMRI (P=0.037). All of the nodules with SPINK1 overexpression were visible on
      mpMRI, although the association was not statistically significant (P=0.06). There
      were no significant associations between any molecular alteration with the
      severity of the PI-RADS scores (all P>0.05). CONCLUSIONS: This investigation
      represents the first description of an association between recurrent molecular
      alterations and the characterization of PCa nodules on mpMRI. This study can be
      considered hypothesis-generating for future studies to rigorously evaluate the
      association of specific PCa molecular subclasses with imaging features and
      potentially define specific subsets of PCa for which the utility of MRI is higher
      or lower.

PMID- 28762375
TI  - Idiosyncratic Drug Induced Liver Injury in African-Americans Is Associated With
      Greater Morbidity and Mortality Compared to Caucasians.
AB  - OBJECTIVES: Idiosyncratic drug induced liver injury (DILI) is a rare but
      potentially serious liver disorder and a major cause of significant liver injury.
      Limited data exist on racial differences in DILI incidence, presentation, and
      course. METHODS: We compared the causative agents, clinical features, and
      outcomes of DILI among self-described African-Americans and non-Hispanic whites
      (Caucasians) enrolled in the DILIN Prospective Study. Individuals with definite,
      highly likely, or probable DILI enrolled between September 2004 and February 2016
      were included in this analysis. RESULTS: 144 African-Americans and 841 Caucasian
      patients met the eligibility criteria. Causal medications varied by race:
      trimethoprim/sulfamethoxazole being the most common cause among African-Americans
      (7.6 vs. 3.6%) followed by methyldopa (4 vs. <1%), phenytoin (5 vs. <1%),
      isoniazid (4 vs. 4%), and amoxicillin/clavulanate (4.1 vs. 13.4%). The severity
      of illness, however, tended to be greater in African-Americans than Caucasians as
      determined by peak mean bilirubin (14.3 vs. 12.8 mg/dl), INR (1.9 vs. 1.6), and
      DILIN severity score (3.0 vs. 2.6). The frequency of severe cutaneous reactions
      was significantly higher in African-Americans (2.1 vs. 0.36% in Caucasians,
      P=0.048). African-Americans also had higher rates of hospitalization (76.7 vs.
      57.6%, P<0.001), liver transplantation or liver related death by 6 months (10.2
      vs. 5.8%, P=0.02 after controlling for selected covariates), and chronic DILI (24
      vs. 16%, P=0.06). CONCLUSIONS: The most common DILI causative agents differ
      between African-Americans and Caucasians. African-Americans are more likely to
      have severe cutaneous reactions and more severe liver injury leading to worse
      outcomes, including death and liver transplant.

PMID- 28762376
TI  - Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta
      analysis.
AB  - Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of
      this study was to examine the magnitude and temporality of this association. We
      searched MEDLINE and EMBASE for observational studies investigating the
      association between chronic pancreatitis and pancreatic cancer. We computed
      overall effect estimates (EEs) with associated 95% confidence intervals (CIs)
      using a random-effects meta-analytic model. The EEs were stratified by length of
      follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period).
      Robustness of the results was examined in sensitivity analyses. We identified 13
      eligible studies. Pooled EEs for pancreatic cancer in patients with chronic
      pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with
      pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The
      risk of pancreatic cancer in patients with chronic pancreatitis decreased when
      the lag period was increased to 5 years (EE: 7.90; 95% CI: 4.26-14.66) or a
      minimum of 9 years (EE: 3.53; 95% CI: 1.69-7.38). In conclusion, chronic
      pancreatitis increases the risk of pancreatic cancer, but the association
      diminishes with long-term follow-up. Five years after diagnosis, chronic
      pancreatitis patients have a nearly eight-fold increased risk of pancreatic
      cancer. We suggest that common practice on inducing a 2-year lag period in these
      studies may not be sufficient. We also recommend a close follow-up in the first
      years following a diagnosis of chronic pancreatitis to avoid overlooking a
      pancreatic cancer.

PMID- 28762378
TI  - Corrigendum: ACG and CAG Clinical Guideline: Management of Dyspepsia.

PMID- 28762377
TI  - Fecal Incontinence Is Associated With Mortality Among Older Adults With Complex
      Needs: An Observational Cohort Study.
AB  - OBJECTIVES: Fecal incontinence (FI) is a problem in growing older populations.
      Validating a suspected association between FI and mortality in community dwelling
      older adults could lead to improved planning for and management of the increasing
      complex older population. In a large cohort of New Zealand older adults, we
      assessed the prevalence of FI, urinary incontinence (UI), combined FI and UI, and
      their associations with mortality. METHODS: This study consisted of a
      retrospective analysis of international standardized geriatric assessment-home
      care (InterRAI-HC) data from community-dwelling adults aged 65 years or older,
      who met the criteria required for the InterRAI-HC, having complex needs and being
      under consideration for residential care. The prevalence of UI and FI was
      analyzed. Data were adjusted for demography and 25 confounding factors. Mortality
      was the primary outcome measure. RESULTS: The total cohort consisted of 41,932
      older adults. Both UI and FI were associated with mortality (P<0.001), and risk
      of mortality increased with increased frequency of incontinence. In the adjusted
      model, FI remained significantly related to survival (P<0.001), whereas UI did
      not (P=0.31). Increased frequency of FI was associated with an increased
      likelihood of death (hazard ratio 1.28). CONCLUSIONS: This large national study
      is the first study to prove a statistically significant relationship between FI
      and mortality in a large, old and functionally impaired community. These findings
      will help improve the management of increasingly complex older populations.

PMID- 28762379
TI  - Characterizing Normal Bowel Frequency and Consistency in a Representative Sample
      of Adults in the United States (NHANES).
AB  - OBJECTIVES: Our current understanding of normal bowel patterns in the United
      States (US) is limited. Available studies have included individuals with both
      normal and abnormal bowel patterns, making it difficult to characterize normal
      bowel patterns in the US. The current study aims to (1) examine frequency and
      consistency in individuals with self-reported normal bowel habits and (2)
      determine demographic factors associated with self-reported normalcy. METHODS:
      This study used data from adult participants who completed bowel health questions
      as part of the National Health and Nutrition Examination Survey (NHANES) in 2009
      2010 and who reported normal bowel patterns (N=4,775). Data regarding self
      perceived bowel health; stool frequency; stool consistency (using the Bristol
      Stool Form Scale (BSFS)); and demographic factors were analyzed. RESULTS: 95.9%
      of the sample reported between 3 and 21 BMs per week. Among men, 90% reported a
      BSFS between 3 and 5, while for women it was 2-6. After controlling for age, the
      following demographic variables were associated with normalcy: male sex, higher
      education, higher income, <2 daily medications, and high daily fiber intake.
      Hispanic ethnicity was significantly associated with abnormal self-reported bowel
      habits. CONCLUSIONS: This is the first study to evaluate normal bowel frequency
      and consistency in a representative sample of adults in the US. The current
      findings bolster the common "3 and 3" metric of normal frequency (3 BMs/day to 3
      BMs/week) while also suggesting different criteria for normal consistency for men
      and women. Finally, this study provides novel information about demographic
      factors associated with normal frequency and consistency.

PMID- 28762380
TI  - Rasch measurement properties of the Pain Medication Questionnaire in persons with
      spinal cord injury.
AB  - STUDY DESIGN: Secondary analysis of cross-sectional population-based self-report
      data. OBJECTIVE: To determine how well the Pain Medication Questionnaire (PMQ)
      measures risk of pain medication misuse and its precision in separating
      individuals with spinal cord injury (SCI) into meaningful classification
      categories. SETTING: Academic medical center in Southeastern United States.
      METHODS: Data were collected from a population-based registry of SCI (n=971).
      Eligible participants included adults with traumatic SCI with residual effects
      who were at least 1 year post injury and 18 years of age and who had PMQ data in
      which they reported active use of pain medication at the time of the study
      (n=745). RESULTS: Most items (23/26) of the PMQ contributed to a single
      unidimensional construct. Rasch analysis results revealed that the rating scale,
      majority of persons (>93%), and majority of items (20/23) fit the Rasch
      measurement model. The PMQ demonstrated adequate reliability (person reliability
      =0.67) and separated persons into two strata-those likely to misuse pain
      medication and those with low liklihood of misusing pain medication. CONCLUSIONS:
      Findings offer a deeper understanding of the measurement properties of the PMQ as
      a precursor for widespread population-based studies to elucidate the incidence of
      pain medication misuse in persons with SCI. Results also have important research
      and clinical implications for commonly used PMQ total score cut-offs, which may
      misclassify an individual's risk of pain medication misuse.

PMID- 28762381
TI  - Comorbidity and physical activity in people with paraplegia: a descriptive cross
      sectional study.
AB  - STUDY DESIGN: Descriptive cross-sectional study. SETTING: The study was conducted
      in the Spinal Cord Injury Unit of the University Vall d'Hebron Hospital and in
      the Physical Education and Sports Department of the University of Valencia.
      OBJECTIVES: The aim of this study was to quantify the presence of comorbidities
      in spinal cord injury (SCI) subjects who did or did not perform regular physical
      activity (PA) and to identify the relationship between PA and the level of
      comorbidity. METHODS: The sample consisted of patients with complete motor SCI
      (T2-T12), who were fitted with an accelerometer attached to the non-dominant
      wrist for a period of 1 week. The clinical and blood analytic variables were
      selected by an expert panel. RESULTS: In the exploratory analysis, we have found
      differences in the total number of pathologies between active and inactive
      patients, with fewer total pathologies in the active patient group. An
      association was found between the PA level and diabetes mellitus (; P=0.047;
      phi=0.25). We also observed an association between the cardioprotector level of
      high-density lipoprotein (HDL)-cholesterol and PA level (; P=0.057; Phi0.24).
      CONCLUSIONS: Our results suggest that patients considered active showed lower
      total comorbidity than inactive patients and higher protection levels against
      developing cardiovascular comorbidity.

PMID- 28762382
TI  - Spontaneous acute and chronic spinal cord injuries in paraplegic dogs: a
      comparative study of in vivo diffusion tensor imaging.
AB  - STUDY DESIGN: Prospective observational-analytical study. OBJECTIVES: Description
      of diffusion tensor imaging (DTI) metrics obtained from the spinal cord (SC) of
      dogs with severe acute or chronic spontaneous, non-experimentally induced spinal
      cord injury (SCI) and correlation of DTI values with lesion extent of SCI
      measured in T2-weighted (T2W) magnetic resonance imaging sequences. SETTING:
      Hannover, Germany. METHODS: Forty-seven paraplegic dogs, 32 with acute and 15
      with chronic SCI, and 6 disease controls were included. T2W and DTI sequences of
      the thoracolumbar spinal cord were performed. Values of fractional anisotropy
      (FA) and apparent diffusion coefficient (ADC) were obtained from the epicentre of
      the lesion and one SC segment cranially and caudally and compared between groups.
      Pearson's correlation coefficient was calculated between DTI and T2W metrics.
      RESULTS: During acute SCI, FA values were increased (P=0.0065) and ADC values
      were decreased (P=0.0099) at epicentres compared to disease controls. FA values
      obtained from dogs with chronic SCI were lower (P<0.0001 epicentres and caudally;
      P=0.0002 cranially) and ADC showed no differences compared to disease control
      values. Dogs with chronic SCI revealed lower FA and higher ADC compared to dogs
      with acute SCI (P<0.0001 for both values at all localisations). FA values from
      epicentre and cranially to the lesion during chronic SCI correlated with extent
      of lesion (r=0.5517; P=0.0052 epicentres and r=0.6810; P=0.0408 cranially).
      CONCLUSION: Using DTI, differences between acute and chronic stages of
      spontaneous canine SCI were detected and correlations between T2W and DTI
      sequences were found in chronic SCI, supporting canine SCI as a useful large
      animal model.

PMID- 28762385
TI  - CNS cancer: Glioblastoma subtypes revisited.

PMID- 28762383
TI  - Clinical factors associated with C-reactive protein in chronic spinal cord
      injury.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: Determine clinical factors
      associated with plasma C-reactive protein (CRP) in persons with chronic spinal
      cord injury (SCI). SETTING: Veterans Affairs Medical Center in Boston, MA, USA.
      METHODS: Participants provided a blood sample, completed a respiratory health
      questionnaire and underwent dual X-ray absorptiometry (DXA) to assess total and
      regional body fat. Linear regression models were used to assess cross-sectional
      associations with plasma CRP. RESULTS: In multivariable models, factors
      associated with a higher CRP included a greater BMI, urinary catheter use, a
      respiratory illness in the past week and non-white race. Mean CRP also increased
      with decreasing mobility (motorized wheelchair >hand-propelled wheelchair >walk
      with an assistive device >walk independently). Results were similar when
      adjusting for percentage android, gynoid, trunk or total fat mass in place of
      BMI. Level and completeness of SCI was not associated with CRP in multivariable
      models. CONCLUSIONS: Clinical characteristics common in chronic SCI are
      associated with plasma CRP. These factors are more important than the level and
      completeness of SCI and some are potentially modifiable.

PMID- 28762386
TI  - Genetics: Taking single-cell transcriptomics to the bedside.

PMID- 28762387
TI  - Haematological cancer: After ibrutinib, CAR T cells induce responses.

PMID- 28762384
TI  - HER2-positive breast cancer is lost in translation: time for patient-centered
      research.
AB  - No biomarker beyond HER2 itself, which suffers from a low positive predictive
      value, has demonstrated clinical utility in breast cancer, despite numerous
      attempts to improve treatment tailoring for the growing number of anti-HER2
      targeted therapies. This prompted us to examine the body of evidence, using a
      systematic approach, to identify putative predictive biomarkers in HER2-positive
      breast cancer, and discuss the hitherto failure to address the needs of patients.
      In the future, it is hoped immune-based biomarkers will predict benefit from anti
      HER2 treatments in the neoadjuvant and adjuvant settings. In advanced-stage
      disease, the quantification of tumour heterogeneity using molecular-imaging
      technology has generated informative data on the success or failure of the
      antibody-drug conjugate T-DM1. Treatment tailoring remains a high priority, in
      cost-constrained health-care systems, but such tailoring will require a dramatic
      shift in the way translational research is being conducted, with the
      establishment of large, easily accessible, and well-annotated databases of
      candidate predictive biomarkers. Single-centre biomarker research should become a
      thing of the past.

PMID- 28762389
TI  - Incontinence: Patients prefer combination therapy.

PMID- 28762388
TI  - Improving outcomes in high-risk, nonmetastatic renal cancer: new data and ongoing
      trials.
AB  - High-risk, localized renal cancer is associated with recurrence rates of up to
      75% at 10 years. The outcomes of patients at this disease stage depend on optimal
      patient stratification, surgical management and systemic therapy selection.
      Current evidence does not support the use of adjuvant therapy in patients with
      high-risk, localized disease. During the past 12 months, the results of large,
      randomized-controlled trials of adjuvant tyrosine kinase inhibitor (TKI)
      treatment, such as ASSURE and S-TRAC, have been published, but their findings are
      conflicting. Whether TKIs will become standard of care in the adjuvant setting
      depends on the long-term data from ongoing trials. In addition, several new
      trials that evaluate the utility of novel immune checkpoint inhibitors in this
      patient group are currently recruiting. The management of renal cancer is likely
      to evolve at a rapid pace over the next few years and matching patients with the
      appropriate therapeutic regimen is likely to be a focus of future research.

PMID- 28762390
TI  - Prostate cancer: A weighty issue: changes in chromatin regulation.

PMID- 28762391
TI  - Kidney cancer: Deciphering sarcomatoid RCC.

PMID- 28762392
TI  - Ionic interaction-induced assemblies of bimolecular "chessboard" structures.
AB  - Here we applied ionic interactions as the driving force to fabricate well-ordered
      bicomponent assemblies by using two porphyrin ions equipped with oppositely
      charged groups. Two kinds of bimolecular chessboard structures were successfully
      constructed on Au(111) and investigated by scanning tunneling microscopy (STM).

PMID- 28762398
TI  - Effect of elimination on antifouling and pH-responsive properties of
      carboxybetaine materials.
AB  - Carboxybetaine (CB)-based zwitterionic materials have attracted considerable
      attention due to their dual antifouling and functionalizable properties. In this
      communication, the elimination effect on the antifouling and pH-responsive
      properties of CB materials was investigated. We synthesize beta- and alpha
      substituted methyl CB materials to investigate the occurrence of elimination in
      the ethylene intercharge arm in a harsh basic solution. This work provides
      molecular understanding of a structure-property relationship of the CB moiety for
      material development.

PMID- 28762399
TI  - Hydrogenated carbon nanotube-based spin caloritronics.
AB  - Spin caloritronics has drawn much attention as it combines thermoelectrics and
      spintronics together. Carbon-based structures, such as graphene, have been found
      to exhibit different kinds of spin caloritronic features. However, a study of
      spin caloritronics in carbon nanotubes (CNTs) is still lacking. Using first
      principles calculations, we investigate the spin-Seebeck effect (SSE) in
      partially hydrogenated CNTs. It is found that linear hydrogenation could make
      CNTs acquire magnetism and exhibit the spin-Seebeck effect. Moreover, an odd-even
      effect of the SSE is observed, where the even cases could be used as spin-Seebeck
      diodes. Further analysis shows that, it is induced by the difference of band
      structures, where the band structure of a tube is a combination of that of
      graphene-nanoribbon parts "divided" by hydrogenation. This mechanism could be
      extended to nanotubes with different diameters, showing great application
      potential. We believe that our results are very useful for the development of
      nanotube-based spin caloritronic devices.

PMID- 28762400
TI  - Interpretation of the A <- X[combining tilde] transition of hydrated protons in
      aqueous solutions observed in the far-UV region with quantum chemical
      calculations.
AB  - Far-ultraviolet spectra (wavelength: 140-200 nm) of group I, II, and XIII cation
      nitrate electrolyte aqueous solutions show that the first electronic transition
      (A <- X[combining tilde]) energies of water hydrating the cations are linearly
      dependent on the hydration energies of the cations. However, deviations from
      these linear relations have been observed only for electrolyte solutions of small
      cations, i.e., H+, Li+, and Be2+ (T. Goto, A. Ikehata, Y. Morisawa, N. Higashi
      and Y. Ozaki, Phys. Chem. Chem. Phys., 2012, 14, 8097-8104). In this study, the A
      <- X[combining tilde] transitions of group I cation-water clusters holding the
      first and second shell water molecules around the cations (M+(H2O)6, M+: H+, Li+,
      Na+, and K+) were studied with quantum chemical calculations to elucidate the
      cation size effects on the electronic states of each shell water molecule. The
      calculation results show that the A <- X[combining tilde] transitions of the
      small cation clusters, especially H+, are more intensely split than those of the
      larger cation clusters, because of the difference in the A <- X[combining tilde]
      transition of each shell and the asymmetric structure of H+(H2O)6. Specifically,
      the A <- X[combining tilde] transitions of the first shell water molecules are
      mostly ascribed to the charge transfer transition of the nonbonding electrons to
      the central cations, while those of the second shell water molecules are ascribed
      to the transition to the sigma* orbitals of the second shell water molecules.
      Moreover, the condensed and distorted structure of H+(H2O)6 causes an
      asymmetrically delocalized electronic distribution in the excited state, as well
      as the ground state, because the electronic interference from the second shell
      water molecules weakens the exciton-hole interaction of the first shell. These
      interpretations based on calculations provide a detailed explanation concerning
      the substantial blue-shift of the A <- X[combining tilde] band of aqueous
      sulfuric acid solutions.

PMID- 28762401
TI  - A one-pot tandem chemoselective allylation/cross-coupling via temperature control
      of a multi-nucleophile/electrophile system.
AB  - A chemoselective tandem reaction of a multi-reactive, two electrophile + two
      nucleophile, system is reported. An allylation/cross-coupling process of a
      haloaryl aldehyde, an aryl BPin, and an allyl BPin can be controlled using a
      temperature gradient to overcome natural reactivity profiles and allow two
      sequential chemoselective C-C bond formations without intervention. This process
      offers efficient access to an array of functionalised products including
      pharmaceutical and natural product scaffolds.

PMID- 28762402
TI  - Selective alpha-arylation of alpha,beta-unsaturated imides mediated by a visible
      light photoredox catalyst.
AB  - Visible light-mediated alpha-arylation of alpha,beta-unsaturated imides is
      achieved via aminium radicals generated from diarylalkylamines using a photoredox
      catalyst. On the basis of emission quenching experiments, a plausible pathway of
      the reaction is discussed.

PMID- 28762403
TI  - Catalysis by solvation rather than the desolvation effect: exploring the
      catalytic efficiency of SAM-dependent chlorinase.
AB  - Chlorinase SalL halogenate S-adenosyl-l-methionine (SAM) reacts with chloride to
      generate 5'-chloro-5'-deoxyadenosine and l-methionine through a nucleophilic
      substitution mechanism. Although it is known that chlorinase enhances the rate of
      reaction by a factor of 1.2 * 1017 fold, it is not entirely clear how this is
      accomplished. The search for the origin of the catalysis of chlorinase and other
      enzymes has led to a desolvation hypothesis. In the present work, we have used
      well defined computational simulations in order to evaluate the origin of the
      catalytic efficiency of chlorinase. The results demonstrate that the catalytic
      effect of chlorinase is associated with the fact that Cl- is "solvated" by the
      protein more than by the reference solution reaction, which is not in accordance
      with proposed catalysis by desolvation. It is found that chlorinase SalL active
      sites provide electrostatic stabilization of the transition state which is the
      origin of its catalytic effect.

PMID- 28762404
TI  - Coherent quantum scattering of CH4 from Ni(111).
AB  - We have measured high-resolution angular distributions of methane scattered from
      a Ni(111) surface at incident energies between 68.9 meV and 108.6 meV. A sharp
      and intense specular peak has been observed, in addition to sharp features
      corresponding to rotationally inelastic diffraction (RID) peaks along the two
      main symmetry directions of Ni(111). The intensity of the most intense RID peaks
      is ca. 50% of the specular one. The observation of sharp, coherent elastic peaks
      at such low incident energies suggests that single scattering dominates over
      trapping at these energies, and that the depth of the van der Waals well should
      be lower than 60 meV. In contrast, a broad angular distribution shifted from the
      specular position is observed from a graphene-covered Ni(111) surface under
      identical incident conditions. These results open up the possibility of studying
      the physisorption well between CH4 and a transition metal surface using high
      resolution molecular beams.

PMID- 28762405
TI  - Directing group assisted copper-mediated aroylation of phenols using 2
      bromoacetophenones.
AB  - A new directing group assisted method for the synthesis of aryl esters is
      described. In this Cu(ii)-mediated reaction, 2-formylphenols and 2-acetylphenols
      are easily converted into aryl esters via treatment with a new aroylating agent 2
      bromoacetophenone. In addition, a new external bromine free method for the
      synthesis of important synthons 2,2-dibromoacetophenones from 2
      bromoacetophenones is described.

PMID- 28762406
TI  - Active colloids with collective mobility status and research opportunities.
AB  - The collective mobility of active matter (self-propelled objects that transduce
      energy into mechanical work to drive their motion, most commonly through fluids)
      constitutes a new frontier in science and achievable technology. This review
      surveys the current status of the research field, what kinds of new scientific
      problems can be tackled in the short term, and what long-term directions are
      envisioned. We focus on: (1) attempts to formulate design principles to tailor
      active particles; (2) attempts to design principles according to which active
      particles interact under circumstances where particle-particle interactions of
      traditional colloid science are augmented by a family of nonequilibrium effects
      discussed here; (3) attempts to design intended patterns of collective behavior
      and dynamic assembly; (4) speculative links to equilibrium thermodynamics. In
      each aspect, we assess achievements, limitations, and research opportunities.

PMID- 28762407
TI  - Probing T1-T2 interactions and their imaging implications through a thermally
      responsive nanoprobe.
AB  - The complex and specialised diagnostic process through magnetic resonance imaging
      (MRI) could be simplified with the implementation of dual T1-T2 contrast agents.
      T1- and T2-weighted MR are compatible modalities, and co-acquisition of contrast
      enhanced images in both T1 and T2 will drastically reduce artefacts and provide
      double-checked results. To date, efforts in the development of dual MRI probes
      have provided inconsistent results. Here we present the preparation and
      relaxometric study of a dual T1-T2 MRI probe based on superparamagnetic
      nanoparticles, paramagnetic Gd3+ chelates and pNIPAM (poly(N
      isopropylacrylamide)), in which the distance between paramagnetic and
      superparamagnetic species can be modulated externally via temperature variations.
      Such a probe alleviates traditional nanotechnology limitations (e.g. batch to
      batch variability) as comparisons can be established within a single probe.

PMID- 28762408
TI  - Synthesis and fluorescence spectroscopy of tris(pyrenyl)pnictogen compounds.
AB  - The synthesis, characterization, and fluorescence spectroscopy of E(C16H9)3
      complexes (E = P, As, Sb, and Bi), as well as OP(C16H9)3, OAs(C16H9)3, and
      SP(C16H9)3, is reported. These compounds exhibit fluorescence quantum yields that
      span two orders of magnitude, from well below 1% to ca. 14%.

PMID- 28762409
TI  - Organic-free synthesis of zincoaluminosilicate zeolites from homogeneous gels
      prepared by a co-precipitation method.
AB  - Zeolites containing Zn in their frameworks are promising materials for ion
      exchange and catalysis because of their unique ion-exchange capabilities and
      characteristic Lewis acidity. However, expensive organic compounds often required
      in their synthesis can prevent their practical uses. Here, a facile organic-free
      synthesis route for new zincoaluminosilicate zeolites having MOR topology, in
      which both Zn and Al are substituted in the framework, is demonstrated for the
      first time. The use of homogeneous zincoaluminosilicate gels prepared by a co
      precipitation technique as raw materials is vital for the successful
      incorporation of both Zn and Al into the zeolite frameworks as revealed by
      several characterization techniques including solid-state NMR and UV-vis
      spectroscopy, and ion-exchange experiments. The obtained zincoaluminosilicate
      zeolites had high Zn contents comparable to those in the initial
      zincoaluminosilicate gels. In contrast, the uses of conventional sources of Si,
      Al, and Zn resulted in zeolites with very low contents of framework Zn or
      zeolites with extra-framework zinc oxide-species. FT-IR measurements using probe
      molecules and ion-exchange experiments suggested that there are two different
      environments of Zn in the zeolite frameworks. The obtained zincoaluminosilicate
      zeolites showed a higher ion-exchange efficiency for divalent cations such as
      nickel compared to the aluminosilicate analog. It is expected that the present co
      precipitation technique is efficient for the incorporation of Zn (and other
      metals) into a variety of zeolite frameworks. To show its extended applicable
      scope, the synthesis of zincoaluminosilicate *BEA zeolite is also demonstrated.

PMID- 28762411
TI  - Structural and mechanistic studies of the base-induced Sommelet-Hauser
      rearrangement of N-alpha-branched benzylic azetidine-2-carboxylic acid-derived
      ammonium salts.
AB  - The base-induced Sommelet-Hauser rearrangement of N-alpha-branched benzylic
      azetidine-2-carboxylic acid ester-derived ammonium salts to obtain alpha
      arylazetidine-2-carboxylic acid esters was investigated. The substrates, two
      diastereomeric salts (1S,2S,1'S)- and (1R,2R,1'S)-2, showed different
      reactivities. The rearrangement of (1S,2S,1'S)-2a proceeded with a perfect N-to-C
      chirality transfer to provide (R)-3a in 74% yield with 99% ee. However, the
      rearrangement of (1R,2R,1'S)-2a under the same conditions afforded (S)-3a in only
      15% yield with a lower 66% ee, along with the competitive [1,2] Stevens
      rearrangement product 4a. Structural and mechanistic studies of this
      rearrangement were carried out to clarify the exact reason. Our results define
      the scope and limitations of the Sommelet-Hauser rearrangement and provide unique
      synthetic access to alpha-aryl amino acid derivatives.

PMID- 28762410
TI  - Accurate nanoscale flexibility measurement of DNA and DNA-protein complexes by
      atomic force microscopy in liquid.
AB  - The elasticity of double-stranded DNA (dsDNA), as described by its persistence
      length, is critical for many biological processes, including genomic regulation.
      A persistence length value can be obtained using atomic force microscopy (AFM)
      imaging. However, most AFM studies have been done by depositing the sample on a
      surface using adhesive ligands and fitting the contour to a two-dimensional (2D)
      wormlike chain (WLC) model. This often results in a persistence length
      measurement that is different from the value determined using bulk and single
      molecule methods. We describe a method for obtaining accurate three-dimensional
      (3D) persistence length measurements for DNA and DNA-protein complexes by using a
      previously developed liquid AFM imaging method and then applying the 3D WLC
      model. To demonstrate the method, we image in both air and liquid several
      different dsDNA constructs and DNA-protein complexes that both increase (HIV-1
      Vpr) and decrease (yeast HMO1) dsDNA persistence length. Fitting the liquid AFM
      imaging contour to the 3D WLC model results in a value in agreement with
      measurements obtained in optical tweezers experiments. Because AFM also allows
      characterization of local DNA properties, the ability to correctly measure global
      flexibility will strongly increase the impact of measurements that use AFM
      imaging.

PMID- 28762412
TI  - Rendering cross-conjugated azophenine derivatives emissive to probe the silent
      photophysical properties of emeraldine.
AB  - An azophenine derivative was synthesized by coupling truxene and azophenine via
      the copper-free Sonagashira reaction using Pd2(dba)3 and As(PPh)3 as catalysts.
      The crystal structure of this heavy azophenine model (~4000) was made and the
      identity of the structure was confirmed. By introducing truxene groups into this
      cross-conjugated structure, the deactivating rotations around the NH-C6H4 bonds
      were slowed down, which rendered this derivative near-IR emissive at 298 K. This
      species provided then the appropriate spectral and kinetic signatures for knowing
      where and what to look for in emeraldine, which was called non-emissive. Besides,
      two other compounds were also synthesized as models for this azophenine
      derivative for comparison and interpretation purposes.

PMID- 28762413
TI  - Two dimensional covalent organic framework materials for chemical fixation of
      carbon dioxide: excellent repeatability and high selectivity.
AB  - Two dimensional (2D) metalloporphyrin-based covalent organic framework (COF)
      composites were synthesized and employed to catalyze the coupling of CO2 and
      epoxides to form cyclic carbonates. With the aid of a co-catalyst, a satisfactory
      selectivity (~100%) and activity (99.2%) for the synthesis of 1,2-butylene
      carbonate were obtained on COF-366-Zn under mild reaction conditions. Their great
      recyclability and adaptability for various substrates were also demonstrated. The
      excellent performance may be benefited from their unique 2D COF structure and the
      facilitation effects on central metalloporphyrin sites from the internal
      environment of COFs.

PMID- 28762414
TI  - Synthesis of a Ni2P/Ni12P5 bi-phase nanocomposite for the efficient catalytic
      reduction of 4-nitrophenol based on the unique n-n heterojunction effects.
AB  - A novel heterostructure catalyst of Ni2P/Ni12P5 has been fabricated through a
      simple solvothermal method by modifying the molar ratio of the initial raw
      materials. The products are characterized by X-ray powder diffraction (XRD),
      field emission scanning electron microscopy (FE-SEM), high-resolution
      transmission electron microscopy (HRTEM), nitrogen adsorption and X-ray
      photoelectron spectroscopy (XPS). It is found that the two phases, Ni2P and
      Ni12P5, are interlaced with one another in the as-formed nanocomposite, resulting
      in more interfaces. The bi-phase catalyst exhibits a markedly enhanced catalytic
      activity in the reduction of 4-nitrophenol, as compared to that of single Ni2P or
      Ni12P5. The enhanced catalytic activity can be attributed to the unique n-n
      series effects, which result in the increased ease of electron transfer over the
      Ni2P/Ni12P5 bi-phase catalyst.

PMID- 28762415
TI  - Biocompatible 3D printed polymers via fused deposition modelling direct C2C12
      cellular phenotype in vitro.
AB  - The capability to 3D print bespoke biologically receptive parts within short time
      periods has driven the growing prevalence of additive manufacture (AM) technology
      within biological settings, however limited research concerning cellular
      interaction with 3D printed polymers has been undertaken. In this work, we used
      skeletal muscle C2C12 cell line in order to ascertain critical evidence of
      cellular behaviour in response to multiple bio-receptive candidate polymers;
      polylactic acid (PLA), acrylonitrile butadiene styrene (ABS), polyethylene
      terephthalate (PET) and polycarbonate (PC) 3D printed via fused deposition
      modelling (FDM). The extrusion based nature of FDM elicited polymer specific
      topographies, within which C2C12 cells exhibited reduced metabolic activity when
      compared to optimised surfaces of tissue culture plastic, however assay viability
      readings remained high across polymers outlining viable phenotypes. C2C12 cells
      exhibited consistently high levels of morphological alignment across polymers,
      however differential myotube widths and levels of transcriptional myogenin
      expression appeared to demonstrate response specific thresholds at which varying
      polymer selection potentiates cellular differentiation, elicits pre-mature early
      myotube formation and directs subsequent morphological phenotype. Here we
      observed biocompatible AM polymers manufactured via FDM, which also appear to
      hold the potential to simultaneously manipulate the desired biological phenotype
      and enhance the biomimicry of skeletal muscle cells in vitro via AM polymer
      choice and careful selection of machine processing parameters. When considered in
      combination with the associated design freedom of AM, this may provide the
      opportunity to not only enhance the efficiency of creating biomimetic models, but
      also to precisely control the biological output within such scaffolds.

PMID- 28762416
TI  - Correlations between preparation methods, structural features and electrochemical
      Li-storage behavior of reduced graphene oxide.
AB  - Wide differences in the structural features of graphenic carbon, especially in
      the case of reduced graphene oxides (rGO), are expected to have considerable
      impacts on the properties, thus leading to significant scatter and poor
      understanding/prediction of their performances for various applications,
      including as electrode materials for electrochemical Li-storage. In this context,
      the present work develops a comprehensive understanding (via thorough
      experimentation, including in situ X-ray diffraction studies, and analysis) on
      the effects of graphene oxide (GO) reduction methods/conditions on the structural
      features (mainly 'graphenic' ordering) and concomitant influences of the same on
      electrochemical Li-storage behavior. 'Moderately oxidized' GO (O/C ~0.41) was
      reduced via three different methods, viz., (i) using hydrazine hydrate vapor at
      room temperature (rGO-H; O/C ~0.23), (ii) thermal reduction by annealing at just
      500  degrees C (rGO-A; O/C ~0.20) and (iii) hydrazine treatment, followed by the
      same annealing treatment (rGO-HA; O/C ~0.17). Raman spectroscopy, in situ X-ray
      diffraction recorded during annealing and high resolution TEM imaging indicate
      that while GO and rGO-H had considerable defect contents [I(D)/I(G) ~1.4 for rGO
      H], including a very non-uniform interlayer spacing (varying between 3.1 and 3.6
      A), the 500  degrees C annealed rGO-A and rGO-HA had significantly reduced defect
      contents [I(D)/I(G) ~0.6] and near-perfect 'graphenic' ordering with a uniform
      interlayer spacing of ~3.35 A. Despite the nanoscaled dimensions, defect
      structures, especially the non-uniform interlayer spacing, resulted in relatively
      poor reversible Li-capacity and rate capability for the non-annealed rGO-H, even
      in comparison to the bulk graphitic carbon. By contrast, the annealed rGOs,
      especially the rGO-HA, not only possessed a superior reversible Li-capacity of
      ~450 mA h g-1 (at C/20), but also exhibited a significantly improved rate
      capability (even compared to most rGOs reported in the literature), retaining
      ~120 mA h g-1 along with flat potential profile (below ~0.2 V against Li/Li+)
      even at 10C (as possibly never reported before with graphitic/graphenic carbons).

PMID- 28762417
TI  - The recent achievements of redox-neutral radical C-C cross-coupling enabled by
      visible-light.
AB  - Visible-light photoredox catalysis has been esteemed as one sustainable and
      attractive synthetic tool. In the past four years, a new yet challenging trend,
      visible-light-driven redox-neutral radical C-C cross-coupling involving putative
      radical intermediates, has been booming rapidly. Its advent brings a powerful
      platform to achieve non-classical C-C connections, and should lead to fundamental
      changes in retrosynthetic analysis. In this tutorial review, we highlight the
      recent achievements of visible-light-mediated redox-neutral radical C(sp3)
      C(sp2), C(sp3)-C(sp), and C(sp3)-C(sp3) bond formation, opening a new window for
      C-C cross-coupling through the photoredox electron shuttling cycle between two
      coupling partners. While radical-radical coupling steered by the persistent
      radical effect was proposed as a rational explanation for the redox-neutral
      photoredox events, alternative kinetically driven chain propagation and radical
      addition pathways cannot be ruled out. This tutorial review aims to highlight the
      recent achievements of photoredox-neutral radical C-C coupling in synthetic
      chemistry.

PMID- 28762418
TI  - Correction: Analysis of local molecular motions of aromatic sidechains in
      proteins by 2D and 3D fast MAS NMR spectroscopy and quantum mechanical
      calculations.
AB  - Correction for 'Analysis of local molecular motions of aromatic sidechains in
      proteins by 2D and 3D fast MAS NMR spectroscopy and quantum mechanical
      calculations' by Piotr Paluch et al., Phys. Chem. Chem. Phys., 2015, 17, 28789
      28801.

PMID- 28762419
TI  - Efficient 3He/4He separation in a nanoporous graphenylene membrane.
AB  - Helium-3 is a precious noble gas, which is essential in many advanced
      technologies such as cryogenics, isotope labeling and nuclear weapons. The
      current imbalance of 3He demand and supply shortage leads to the search for an
      efficient membrane with high performance for 3He separation. In this study, based
      on first-principles calculations, we demonstrated that highly efficient 3He
      harvesting can be achieved in a nanoporous graphenylene membrane with
      industrially-acceptable selectivity and permeance. The quantum tunneling effect
      leads to 3He harvesting with high efficiency via kinetic sieving. Both the
      quantum tunneling effect and zero-point energy (ZPE) determine the 3He/4He
      separation via thermally-driven equilibrium sieving, where the ZPE effect
      dominates efficient 3He/4He separation between two reservoirs. The quantum
      effects revealed in this work suggest that the nanoporous graphenylene membrane
      is promising for efficient 3He harvesting that can be exploited for industrial
      applications.

PMID- 28762420
TI  - A novel alb metalloring organic framework with a {Ni12Gd24} cage exhibiting a
      significant magnetocaloric effect.
AB  - With the aid of a bifunctional 6-mercaptonicotinic acid ligand, a novel
      {Ni12Gd24} cage-based (6, 12)-c alb-MROF that is assembled from a
      {Gd4(OH)4(COO)6} trigonal-prism building unit and a {Ni6S12} hexagonal-prism
      molecular building block has been synthesized for the first time. It exhibits a
      large MCE value of 29.86 J kg-1 K-1 for DeltaH = 8 T at 2 K.

PMID- 28762421
TI  - Development of optimum p-nc-Si window layers for nc-Si solar cells.
AB  - p-Type nc-Si (p-nc-Si) films have been optimized under low growth temperature
      (~180  degrees C) and low power (~30 W) parametric conditions in 13.56 MHz RF
      PECVD. At elevated gas pressure (p), the growth rate enhances; however, the
      optical band gap reduces. At optimum p = 2.5 Torr, a p-nc-Si window-layer
      possessing high crystallinity, large grain size, high electrical conductivity,
      wide optical band gap and a preferred <220> crystallographic orientation of the
      nanocrystallites is obtained. Single p-i-n junction nc-Si solar cells in
      superstrate configuration have been realized with reasonably acceptable
      conversion efficiency, eta ~ 7.05%. The preferred <220> oriented (I<220>/I<111> ~
      1.68) highly crystalline (XC ~ 86%) p-nc-Si window-layer minimizes the lattice
      mismatch at the p/i-junction, facilitates the growth of proper crystallinity in
      the i-nc-Si absorber layer from its incubation stage during its sequential growth
      over the window layer and ensures low recombination losses for conduction of
      charge carriers along the vertical direction at the p/i-interface. Further
      improvement in cell efficiency sensitively depends on proper optimization and
      future ungradation of the i-nc-Si absorber layer, and the single junction nc-Si
      cell could play a significant role as an integral part of premium all-Si tandem
      structure solar cells.

PMID- 28762422
TI  - The gas-phase structure of dimethyl peroxide.
AB  - There has been a disagreement amongst experimentalists and between
      experimentalists and theoreticians as to the gas-phase structure of dimethyl
      peroxide. We have investigated this problem with high-level CCSD(T)-F12 and MRCI
      procedures. There can be no doubt anymore that, at the minimum of the potential
      energy surface, the COOC fragment has a trans-structure. The dynamical structure
      of the molecule can, however, be different and be explained by the very slow
      torsional motion. We have analysed the dynamical structure using numerical
      wavefunctions of the torsional motion and a fully optimized potential curve of
      MP2/aug-cc-pVTZ quality. Computational and all experimental results are shown to
      be in complete agreement. The problem that has persisted for more than thirty
      years, highlighted in a recent review article by Oberhammer titled "Gas phase
      structures of peroxides: experiments and computational problems", has been
      resolved.

PMID- 28762423
TI  - Approaching complexity of alkyl hydrogenation on Pd via density-functional
      modelling.
AB  - Pd is widely used to catalyse hydrogenation and dehydrogenation reactions. One of
      them is the hydrogenation of ethylene, which includes the transformation of ethyl
      species to ethane. Herein, by means of density-functional calculations we address
      several still insufficiently understood factors affecting the latter process. In
      particular, we shed light on the following aspects of hydrogenation of alkyls on
      Pd: (i) the mechanistic details of how subsurface H accelerates the reaction on a
      (111) surface; (ii) the role of nanoparticle edges; and (iii) the influence of a
      common spectator ethylidyne, [triple bond, length as m-dash]C-CH3. These factors
      are identified as significant for the height of the ethyl hydrogenation barrier
      on Pd. Moreover, we show that butyl hydrogenation on Pd is also governed by very
      similar interactions, which suggests a broader applicability of our conclusions.
      This study highlights the complexity of alkyl hydrogenation and analyses the
      factors that need to be taken into account for a more realistic description of
      the hydrogenation processes on metal surfaces.

PMID- 28762424
TI  - Low temperature conductivity and ion dynamics in silver iodide-silver
      metaphosphate glasses.
AB  - Silver iodide-silver metaphosphate glasses xAgI.(1 - x)AgPO3 (x = 0.3, 0.4, and
      0.5) have been prepared using the usual melt quenching method. Differential
      scanning calorimetry has been used to determine the glass transition temperature
      of the samples. Impedance spectroscopy spanning wide temperature (20 K to 200 K)
      and frequency (10-1 Hz to 106 Hz) ranges has been employed to investigate the ion
      dynamics. At high temperatures, below the glass transition temperature and down
      to around 120 K, the dynamics show the usual behavior of dc and dispersed
      conductivity due to the random and correlated motion of the ions. The dc
      conductivity of the glasses varies dramatically and it increases with the AgI
      content as expected. At the lowest temperatures investigated, however, the
      conductivity of the glasses was indistinguishable. Hence, the low temperature
      dynamics are identical irrespective of the amount of AgI and the structure of the
      glass. In addition, a nearly constant loss behavior, independent of the
      temperature and composition, was attained at the lowest temperatures.

PMID- 28762426
TI  - Considerable humidity response of a well-aligned SOMS micro-wire flexible sensor
      by moisture-induced releasing of trapped electrons.
AB  - Sandia Octahedral Molecular Sieves micro-wires (SOMS MWs) that exhibit ultra-high
      response to moisture and a short response time can be produced easily in an
      environmentally friendly mass production process. They are excellent candidate
      materials for use in humidity sensors. SOMS MWs were synthesized using niobium
      pentoxide as a precursor in concentrated sodium hydroxide solution. To fabricate
      humidity-sensing devices, electrophoresis was utilized to align the SOMS MWs on a
      polyethylene terephthalate (PET) substrate. The degree of alignment of SOMS MWs
      can be tuned by controlling the electric field during electrophoresis. Both well
      aligned SOMS MWs (S-1.00) and randomly distributed SOMS MWs (S-0.00) exhibit
      maximum sensitivities to humidity (RRH/RDRY) of almost 104 and 107 respectively,
      and both exhibit short response times (34 and 38 s) and recovery times (7 and 10
      s); these MWs outperform metal oxide ceramic-based materials in sensing humidity.
      Furthermore, the humidity response of S-1.00 exceeds that of S-0.00 by three
      orders of magnitude, and this result cannot be explained with reference to the
      Grotthuss mechanism. Therefore, the moisture-induced carriers from trapped
      electrons contribute significantly to the humidity response of SOMS MWs. In
      addition, with outstanding humidity sensing-performance under extreme bending
      conditions and superior durability after being bent hundreds of times, the well
      aligned SOMS MW sensor is a favorable candidate for emerging multifunctional
      electronic-skin.

PMID- 28762425
TI  - Comparison of air samplers for determination of isocyanic acid and applicability
      for work environment exposure assessment.
AB  - Isocyanic acid (ICA) is one of the most abundant isocyanates formed during
      thermal decomposition of polyurethane (PUR), and other nitrogen containing
      polymers. Hot-work, such as flame cutting, forging, grinding, turning and welding
      may give rise to thermal decomposition of said polymers potentially forming
      significant amounts of ICA. A newly launched dry denuder sampler for airborne
      isocyanates using di-n-butylamine (DBA) demonstrated build-up of background ICA
      DBA over time. Build-up of background ICA-DBA was not observed when stored at
      inert conditions (Ar atmosphere) for 84 days. Thus, freshly prepared denuders
      were used. The sampling efficiency of ICA using freshly prepared denuder samplers
      (0.2 L min-1), impinger + filter samplers (0.5 L min-1) using DBA and 1-(2
      methoxyphenyl) piperazine (2MP)-impregnated filter cassette samplers (1 L min-1)
      was investigated. PTR-MS measurements of ICA were used as a quantitative
      reference. Dynamically generated standard ICA atmospheres covered the range 5.6
      to 640 ppb at absolute humidities (AH) 4.0 and 16 g m-3. Recovered ICA was found
      to be 73-115% (denuder), 89-115% (impinger + filter) and 62-100% (2MP filter
      cassette). The method limit of detection (LOD) was equal to an amount of ICA of
      24 ng (denuder), 8.9 ng (impinger + filter) and 9.4 ng (2MP filter cassette). The
      PTR-MS LOD for ICA was 1.8 and 2.8 ppb in atmospheres with an AH of 4 and 16 g m
      3. Denuder samplers were used for personal (n = 176) and stationary (n = 31) air
      sampling during hot-work at six industrial sites (n = 23 workers). ICA was
      detected above method LOD in 66% and 58% of the personal and stationary samples,
      respectively. ICA workroom air concentrations were determined to be 1.8-320 ppb
      (median 12 ppb) (personal samples), and 1.5-44 ppb (median 6.6 ppb) (stationary
      samples).

PMID- 28762427
TI  - Effect of lipid shape on toroidal pore formation and peptide orientation in lipid
      bilayers.
AB  - Amphiphilic peptides of different lengths were simulated with lipid bilayers
      composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1-myristoyl-2
      hydroxy-sn-glycero-3-phosphocholine (lysoMPC) in different ratios. Simulations of
      lipid bilayers without peptides show that the bilayers with more lysoMPC become
      more disordered and thinner. Amphiphilic peptides added to this simulation do not
      insert into the DMPC bilayer at a low peptide/lipid ratio (P/L <= 1/50), while
      they do insert into the DMPC/lysoMPC bilayer and form a toroidal pore even at
      such a low P/L ratio, where the pore edge is surrounded by lysoMPC rather than by
      DMPC. In particular, upon pore formation, peptides migrate toward the edge of a
      pore and become tilted, showing transmembrane alignment regardless of the peptide
      length, in qualitative agreement with experiments. This pore formation occurs
      more frequently in larger bilayers that allow greater curvature, indicating that
      bilayer curvature is important for pore formation. These results indicate that
      the addition of lysoMPC induces a thinner bilayer with greater curvature, and
      thus the bilayer with lysoMPC can be more easily penetrated by peptides, leading
      to the formation of a toroidal pore stabilized by peptides and lysoMPC. These
      findings help explain experimental observations of the effect of the inverted
      cone-shaped lyso-lipid on pore formation and peptide orientation, and also
      support the experimental suggestion regarding the formation of an iris-like ring
      of helices lining a toroidal pore.

PMID- 28762428
TI  - Health empowerment and health rights in Saudi Arabia.
AB  - [No Abstract Available].

PMID- 28762429
TI  - Level of evidence of abdominal surgery clinical research in Saudi Arabia.
AB  - OBJECTIVES: To quantify and evaluate the level of evidence (LOE) of Saudi
      publications in abdominal surgery and correlate the obtained results with that of
      other similar national and international studies. Methods: Study design was a
      systemic review. Literature search strategy was developed to retrieve available
      articles between January 2000 and  December 2016 that are related to abdominal
      surgery utilizing PubMed and Google Scholar. Retrieved articles were analyzed in
      depth with several parameters, then evaluated using (OEBM) level of evidence
      scale. Results: One hundred and ninety-eight articles met the inclusion criteria.
      Of these, 50.5% were level III evidence studies. The most common study design was
      case reports (47%), and academic institutions had the highest rate of
      publications (47%). Conclusion: Saudi research in abdominal surgery published
      between 2000-2016 are of lower quality and of III and IV LOE, which is in the
      consistency with other specialties. We emphasize the need for promotion of a
      national and institutional research studies of I and II LOE with collaboration
      between different health care institutions.

PMID- 28762430
TI  - Determination of lumbosacral transitional vertebrae in kidney urinary bladder x
      ray films in the Saudi population.
AB  - OBJECTIVES: To investigated the rate of occurrence of lumbosacral transitional
      vertebrae (LSTV), spinal variant, in kidney urinary bladder (KUB) plain
      radiographs in a Saudi population.  Methods: Between January 2012 to January
      2015, KUB plain films obtained from patients at King Abdulaziz University
      Hospital, Jeddah, Saudi Arabia, were reviewed, and the presence or absence of
      LSTV was documented and classified as incomplete or complete. Patients who had
      evidence of spinal surgery that would obscure the view were excluded.  Results: A
      total of 2078 patients underwent KUB examinations during the study period; LSTV
      anomalies were detected in 158 of these. Sacralization was present in 153 (96.8%)
      of this cohort, while lumbarization was present in 5 (3.2%). A total of 136
      (86.1%) of the sacralized segments were of the incomplete type, whereas 17
      (10.7%) were complete. Of the lumbarized vertebrae, 3 (1.8%) were incomplete, and
      2 (1.2%) were complete. The most frequent type in men was type Ib (28.5%) for
      sacralized segments, and type IIb for lumbarized segments (0.6%). In women, type
      Ia was the most common form of sacralized segments (11.3%) and type IIb was the
      most common form of lumbarized segments (2.8%). Conclusion: The prevalence of
      LSTV in Saudi patients is 7.6%, with a higher incidence of sacralization than
      lumbarization. Further studies with larger sample sizes and longer follow-up time
      are needed to demonstrate the clinical significance thereof.

PMID- 28762431
TI  - The accuracy of Broselow pediatric emergency tape in estimating body weight of
      pediatric patients.
AB  - OBJECTIVES: To determine the accuracy of the Broselow tape on estimating body
      weights of selected Saudi children. Methods: This is prospective study of
      children aged 7 days to 13 years who attended the Emergency Department of King
      Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Saudi
      Arabia, from June 2015 to September 2015. Only children less than 34 kg were
      enrolled for the study and children with triage categories I and II were
      eliminated to avoid delay in providing appropriate treatment in these
      circumstances.  Results: The relationship between the actual and tape estimated
      body weights showed a correlation coefficient of 0.945 (p less than 0.001) for
      all children. When adjusting the correlation coefficient related to weight
      groups, the correlation coefficient was 0.911 (p less than 0.001) for children
      with body weights between 10 to 25 kg. Conclusion: The Broselow tape measurements
      do not provide satisfactory results for all children in the selected population,
      but do provide highly correlated measurements for those children with body
      weights between 10 and 25 kg.

PMID- 28762432
TI  - Prevalence of uncorrected refractive errors among children aged 3-10 years in
      western Saudi Arabia.
AB  - OBJECTIVES: To determine the prevalence of uncorrected refractive errors (URE)
      among children 3-10 years and to affirm the necessity of a national school-based
      visual screening program for school-aged children. Methods: This retrospective
      cross-sectional study was conducted in Medina, Saudi Arabia in 2015. Children
      were selected through a multistage stratified random sampling from 8 kindergarten
      and 8 primary schools. Those included were screened to diagnose UREs using a
      visual acuity chart and an auto refractometer according to American guidelines.
      The prevalence and types of UREs were estimated. Results: Of the 2121 children
      enumerated, 1893 were examined, yielding a response rate of 89.3%. The prevalence
      of UREs was 34.9% (95% CI = 32.8%-37.1%), with significant differences in
      different age groups. The prevalence of astigmatism (25.3%) was higher compared
      to that of anisometropia (7.4%), hypermetropia (1.5%), and myopia (0.7%). Risk of
      uncorrected refractive error was positively associated with age, and this was
      noted in astigmatism, myopia, and anisometropia. In addition, the risk of
      hypermetropia was associated with boys and that of myopia was associated with
      girls. Conclusions: The prevalence of UREs, particularly astigmatism, was high
      among children aged 3-10 years in Medina, with significant age differences.
      Vision screening programs targeting kindergarten and primary schoolchildren are
      crucial to lessen the risk of preventable visual impairment due to UREs.

PMID- 28762433
TI  - Incidence and molecular characterization of the extended spectrum beta lactamase
      producing Escherichia coli isolated from urinary tract infections in Eastern
      Saudi Arabia.
AB  - OBJECTIVES: To find the prevalence of uropathogenic Escherichia coli (E. coli)
      producing extended spectrum beta lactamase (ESBL) at King Fahd Military Medical
      Complex in Dhahran (KFMMC) and to detect the genes responsible for its
      production. In addition, we determined the pattern of multi-drug resistance among
      isolates. Methods: A total of 117 uropathogenic E. coli isolates were collected
      from KFMMC over a period of 4 months from March 2014 to June 2014. These were
      received in the Microbiology Laboratory at Prince Sultan Military College of
      Health Sciences (PSMCHS), Dhahran, Saudi Arabia for analysis. The isolates were
      screened for ESBL using VITEK(r) 2 Compact. Polymerase chain reaction (PCR) 
      examination was used to determine TEM, SHV, and CTX-M genes.  Results: Our
      findings indicated that there is a high incidence of ESBLs among the E. coli
      isolated from UTI (23.1%). Our study also indicated that CTX-M genes are the most
      prevalent among the isolates at KFMMC followed by TEM class (6%), but there was
      also a higher percentage E. coli (3.4%) simultaneously harboring TEM and CTX
      genes. None of our isolates harbored the SHV genes. Conclusion: The findings
      document the threat of ESBL among E. coli isolates from UTI especially the CTX-M
      class in our hospital with the occurrence of these strains as etiologic agents of
      infection in the hospital and community.

PMID- 28762434
TI  - Identification of risk factors for enteral feeding intolerance screening in
      critically ill patients.
AB  - OBJECTIVES: To identify risk factors for enteral feeding intolerance screening in
      critically ill patients, thereby, provide some reference for healthcare staff to
      assess the risk of feeding intolerance, and lay the foundation for future scale
      development.  Methods: This study used a mixed methodology, including a
      literature review, semi-structured interviews, the Delphi technique, and the
      analytic hierarchy process. We used the literature review and semi-structured
      interviews (n=22) to draft a preliminarily item pool for feeding intolerance,
      Delphi technique (n=30) to screen and determine the items, and the analytic
      hierarchy process to calculate the weight of each item. The study was conducted
      between June 2014 and September 2015 in Daping Hospital, Third Military Medical
      University, Chongqing, China.  Results. Twenty-three risk factors were selected
      for the scale, including 5 dimensions. We assigned a weight to each item
      according to their impact on the feeding intolerance, with a higher score
      indicating a greater impact. The weight of each dimension was decreasing as
      follows: patient conditions, weight score equals 42; general conditions, weight
      score equals 23; gastrointestinal functions, weight score equals 15; biochemical
      indexes, weight score equals 14; and treatment measures, weight score equals 6.
      Conclusion. Developed list of risk factors based on literature review, survey
      among health care professionals and expert consensus should provide a basis for
      future studies assessing the risk of feeding intolerance in critically ill
      patients.

PMID- 28762435
TI  - Awareness of holistic care practices by intensive care nurses in north-western
      Saudi Arabia.
AB  - OBJECTIVES: To examine awareness of holistic patient care by staff nurses in the
      intensive care units of hospitals in the city of Hail, Saudi Arabia.  Methods: A
      quantitative correlational study design was used to investigate relationships
      between intensive care nurse's awareness of holistic practices and nurses' latest
      performance review. Intensive care staff nurses (n=99) from 4 public sector
      hospitals in Hail were surveyed on their awareness of variables across 5 holistic
      domains: physiological, sociocultural, psychological, developmental, and
      spiritual. Data were collected between October and December 2015 using written
      survey, and performance evaluations obtained from the hospital administrations.
      Results were statistically analyzed and compared (numerical, percentage,
      Pearson's correlation, Chronbach's alpha). Results: The ICU staff nurses in Hail
      City were aware of the secular aspects of holistic care, and the majority had
      very good performance evaluations. There were no demographic trends regarding
      holistic awareness and nurse performance. Further, awareness of holistic care was
      not associated with nurse performance.  Conclusion: A caring-enhancement workshop
      and a mentoring program for non-Saudi nurses may increase holistic care awareness
      and enhance its practice in the ICUs.

PMID- 28762436
TI  - Burnout among plastic surgery residents. National survey in Saudi Arabia.
AB  - OBJECTIVES: To develop a more comprehensive explanation and understanding of the
      prevalence of and factors associated with burnout for residents of the Saudi
      Plastic Surgery Residency Program.  Methods: This is a cross sectional study.
      Data was gathered using a survey, which was distributed during April 2015, among
      all 57 plastic surgery residents enrolled in training programs across all regions
      of Saudi Arabia, 38 of whom responded (60% response rate). The dependent variable
      was professional burnout, which was measured by 3 subscales of the validated
      Maslach Burnout Inventory (MBI). High scores on emotional exhaustion (EE) or
      depersonalization (DP) or low scores on personal accomplishment (PA) were taken
      to be indicative of professional burnout. Variables evaluating possible
      predictors of burnout, such as sociodemographic and professional characteristics,
      were also included. Results: The validated rate of high burnout status was 18%.
      Nearly three quarters (71%) of residents scored high in emotional exhaustion, and
      half (50%) scored high in depersonalization. A third (34%) scored low in personal
      accomplishment. However, only 5% were dissatisfied with the plastic surgery
      specialty as a career, and 69% would choose the same specialty again. Workload
      was not found to play a significant role in the development of burnout (mean 70
      hours per week).  Conclusion: Approximately half of plastic surgery trainees in
      the Kingdom of Saudi Arabia have signs of professional burnout.

PMID- 28762437
TI  - A randomized controlled trial of a 12-week intensive lifestyle intervention
      program at a primary care obesity clinic for adults in western Saudi Arabia.
AB  - OBJECTIVES: To assess the ability of a 12-week primary care-based intensive
      lifestyle intervention (ILI), to facilitate a 5% reduction in baseline weight
      compared with an education-only active comparator (AC).  Methods: A randomized
      clinical trial was conducted in a primary health care setting in Jeddah, Saudi
      Arabia between December 2014 and June 2015. Arab participants with obesity, but
      who were otherwise healthy (n=140), were randomized to the ILI (n=70) or AC
      (n=70) group. The ILI group received 8 clinical visits throughout the study. The
      AC group received only an initial health education session. The primary outcome
      was the proportion of participants who achieved clinically significant weight
      loss (>=5% of their baseline weight).  Results: Participants in the ILI group
      were significantly more likely than those in the AC group to achieve the primary
      outcome (p=0.008, relative risk: 1.8 [95% confidence interval [CI]: 1.15 to
      2.93). At week 12, the ILI group exhibited a mean weight decrease of 5.58 +/-
      5.60 kg (-5.37 +/- 5.31%), significantly greater than that observed in the AC
      group (-2.8 +/- 4.96 kg, -2.62 +/- 4.34%, p=0.002), and corresponding to a weight
      loss advantage of 2.77 kg (95% CI: 1.01 to 4.54 kg) or 2.75% (95% CI: 1.13% to
      4.37%).  Conclusion: The 12-week primary care-based ILI program was effective in
      achieving a clinically meaningful weight reduction (>=5%) among Saudi and Arab
      patients with obesity.

PMID- 28762438
TI  - Impact of shift work on sleep and daytime performance among health care
      professionals.
AB  - OBJECTIVES: To evaluate sleep quality and daytime sleepiness in health care
      professionals who are performing shift work. Methods: This cross-sectional study
      was conducted on 510 health care professionals at Prince Sultan Military Medical
      City and King Khalid University Hospital, King Saud University, Riyadh, Kingdom
      of Saudi Arabia between December 2015 and April 2016. Data were collected using
      the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS).
      Participants were divided into 2 groups: shift workers and non-shift workers.
      Results: We compared both groups regarding the effect of shift work on the total
      score of PSQI and ESS. We found that the PSQI global score (p less than 0.001)
      and the total ESS score (p=0.003) were significantly higher in shift work health
      care professionals.  Conclusion: Shift work among health care professionals is
      associated with poor sleep quality but not excessive daytime sleepiness. Health
      care professionals performing shift work have PSQI and ESS scores slightly higher
      than non-shift work health professionals.

PMID- 28762439
TI  - Antibiotic abuse during endodontic treatment in private dental centers.
AB  - OBJECTIVES: We evaluated antibiotic prescription practices during root canal
      treatments among general dentists in private dental clinics in Al-Madinah Al
      Munawarah, Saudi Arabia. Methods: A self-administered, questionnaire about
      antibiotic used during root canal treatment was distributed to 75 randomly
      selected general dental practitioners working in private dental clinics in Al
      Madinah Al-Munawarah, Saudi Arabia, between March and April 2016. The
      questionnaires were collected one week later. To compare results of the collected
      data, Chi-square test was used.  Results: The results revealed that 60% of the
      dentists prescribed amoxicillin with clavulanic acid as the first choice
      treatment for endodontic pathosis. Clindamycin (51.6%) was the first choice for
      patients who were allergic to penicillin. Forty-five percent of the general
      practitioners prescribed antibiotics for 5 days. Approximately 83.3% of general
      practitioners prescribed antibiotics for acute apical abscesses. Prophylactic
      antibiotics were prescribed for cases with a history of infective endocarditis
      (65.5%), non-controlled diabetes (60.3%), placement of a prosthetic joint in the
      previous 2 years (46.6%), congenital heart disease (36.2%), and kidney dialysis
      shunts (34.5%). Conclusion: This study reveals antibiotic abuse in endodontic
      treatment practice in private dental clinics in Al-Madinah Al Munawarah, Saudi
      Arabia. General dental practitioners are lacking knowledge regarding the
      prescription of antibiotics in endodontic  treatment and situations requiring
      prophylactic antibiotics.

PMID- 28762440
TI  - The use of oral and maxillofacial pathology services by general pathologists and
      their attitude towards it in Saudi Arabia.
AB  - OBJECTIVES: To investigate the awareness and usage of oral and maxillofacial
      pathology (OMFP)  subspecialty services among pathologists in Saudi Arabia.
      Methods: In this cross-sectional study, we conducted an electronic questionnaire
      survey of pathologists in all regions of Saudi Arabia. The study was conducted
      between July 2015 and August 2016.  The questionnaire comprised 19 questions to
      evaluate the knowledge of pathologists regarding microscopic OMFP and their
      perceptions towards this subspecialty. Results: Most of the pathologists surveyed
      (94.6%) were aware of the OMFP subspecialty and its scope of practice. Although
      most of the pathologists recognized the importance and need of this subspecialty,
      70% of them never referred or consulted an oral pathologist as they either
      diagnosed the cases themselves or  did not know any oral pathologist (57.7%). The
      pathologists had the greatest difficulty in identifying and diagnosing
      odontogenic tumors, salivary gland tumors, and odontogenic cysts.  Conclusion:
      Pathologists are aware of the OMFP subspecialty, but their utilization of the
      services offered by OMFP specialists in Saudi Arabia is quite low despite the
      strong demand for OMFP services.

PMID- 28762441
TI  - Severe aortic regurgitation complicating Takayasu's arteritis.
AB  - We present an uncommon case of a 48-year-old female patient with symptomatic
      presentation of a severe aortic regurgitation with aneurysm of the ascending
      aorta and progressive dyspnea. Detailed investigation of laboratory tests and
      imaging identified Takayasu's arteritis (TA) as the underlying etiology. Computed
      tomography scan revealed complete occlusion of the right carotid artery as well
      as stenosis at the origins of left subclavian and vertebral arteries. In
      addition, cardiac magnetic resonance angiogram showed aneurysm at the proximal
      segment of right subclavian artery. Intervention with corticosteroids effectively
      diminished the need for immediate surgical intervention. Treating physicians
      should always consider differential diagnosis of TA in the presence of atypical
      clinical findings in all patients with cardiac problems especially when there is
      valve involvement.

PMID- 28762442
TI  - Umrah. An opportunity for mass gatherings health research.
AB  - [No Abstract Available].

PMID- 28762443
TI  - Atypical femoral fractures and biphosphonates.
AB  - [No Abstract Available].

PMID- 28762445
TI  - Abstracts from the 17th Congress of the European Society for Dermatology and
      Psychiatry.

PMID- 28762444
TI  - Long-term use of bisphosphonates in osteoporosis.
AB  - [No Abstract Available].

PMID- 28762446
TI  - Depressive symptoms among older adults with long-term spinal cord injury:
      Associations with secondary health conditions, sense of coherence, coping
      strategies and physical activity.
AB  - OBJECTIVES: To assess the presence of depressive symptoms among older adults with
      long-term spinal cord injury and investigate the association with
      sociodemographic and injury characteristics; and to determine how potentially
      modifiable factors, i.e. secondary health conditions, sense of coherence, coping
      strategies and leisure-time physical activity, are associated with depressive
      symptoms. DESIGN: Cross-sectional study. SUBJECTS: A total of 122 individuals
      (70% men, injury levels C1-L5, American Spinal Injury Association Impairment
      Scale A-D), mean age 63 years, mean time since injury 24 years. METHODS: Data
      from the Swedish Aging with Spinal Cord Injury Study, collected using the
      Geriatric Depression Scale-15, the 13-item Sense of Coherence Scale, the Spinal
      Cord Lesion-related Coping Strategies Questionnaire and the Physical Activity
      Recall Assessment for people with Spinal Cord Injury. Associations were analysed
      using multivariable linear regression. RESULTS: A total of 29% reported
      clinically relevant depressive symptoms and 5% reported probable depression.
      Sense of coherence, the coping strategy Acceptance, neuropathic pain and leisure
      time physical activity explained 53% of the variance in depressive symptoms.
      CONCLUSION: Older adults with long-term spinal cord injury report a low presence
      of probable depression. Mental health may be supported through rehabilitation
      that strengthens the ability to understand and confront life stressors, promotes
      acceptance of the injury, provides pain management and encourages participation
      in leisure-time physical activity.

PMID- 28762447
TI  - Protective effects of dexmedetomidine and remote ischemic preconditioning on
      renal ischemia reperfusion injury in rats.
AB  - BACKGROUND: The aim of this study was to evaluate the effects of remote ischemic
      preconditioning (RIPC) and dexmedetomidine as pharmacological conditioning in a
      rat renal ischemia/reperfusion (IR) injury model. METHODS: Total of 28 male
      Wistar Albino rats weighing 250 to 300 g were divided into 4 equal groups. Group
      I (Sham; n=7): Laparotomy and renal pedicle dissection were performed, and the
      rats were observed under anesthesia without any intervention. Group II (IR; n=7):
      Following laparotomy and 45 minutes of left renal pedicle occlusion, 4 hours of
      reperfusion was performed. Group III (IR+D; n=7): Following laparotomy and
      ischemia, dexmedetomidine was administrated intraperitoneally (100 ug/kg) at
      fifth minute of reperfusion. Group IV (RIPC+IR; n=7): Under anesthesia, 3 cycles
      of ischemic preconditioning were applied to the left hind leg, and after 5
      minutes, renal IR was performed. All rats were sacrificed after the left kidney
      was processed for conventional histomorphology. RESULTS: Total histomorphological
      renal injury score was significantly lower in the Sham group compared with the
      other groups (p<0.01). Total renal injury score of IR group was significantly
      higher than IR+D and RIPC+IR groups (p<0.01). There was no significant difference
      in the total renal injury score between the dexmedetomidine and RIPC groups
      (p=0.89). CONCLUSION: In the present study, it was demonstrated
      histomorphologically that both dexmedetomidine and RIPC decreased renal IR injury
      significantly. In addition, no significant difference was found between
      dexmedetomidine and RIPC groups.

PMID- 28762448
TI  - Comparison of warm fluid and cold fluid resuscitation during uncontrolled
      hemorrhagic shock model in rats.
AB  - BACKGROUND: This study was designed to compare the effects of resuscitation with
      cold and warm fluid on survival time, rate and volume of hemorrhage,
      hemodynamics, hypothermia, coagulopathy, acid-base balance, hematocrit, lactate,
      and base deficit during uncontrolled hemorrhagic shock (HS) model in rats.
      METHODS: HS model was created with splenic vascular and parenchymal injury in 29
      rats under ketamine and xylazine anesthesia. Thirty minutes after the hemorrhage,
      the rats were randomized to receive 14.5 mL/kg 0.9% sodium chloride solution at
      either 24oC (Group 1; n=9) or 4oC (Group 2; n=10) for 20 minutes. Groups 1 and 2
      were compared with group that did not receive fluid (Group 3; n=10). Statistical
      data were represented as mean+/-SD. SPSS for Windows, Version 15.0 (SPSS, Inc.,
      Chicago, IL, USA) software, Bonferroni-adjusted Mann-Whitney U test and Kaplan
      Meier procedure were used to perform statistical data analysis. P value of <=0.05
      was considered statistically significant. RESULTS: Cold fluid resuscitation
      decreased survival time due to increased rate and volume of hemorrhage, acidosis,
      hypothermia, lactate, and base deficit and decreased blood pressure and
      hematocrit. CONCLUSION: There is a great need for further experimental and
      clinical trials on fluid resuscitation in trauma in order to define which fluid
      should be administered, temperature of the fluid, quantity to be delivered, and
      duration.

PMID- 28762449
TI  - The value of internal jugular vein collapsibility index in sepsis.
AB  - BACKGROUND: Rapid, accurate, and reproducible assessment of intravascular volume
      status is crucial in order to predict the efficacy of volume expansion in septic
      patients. The aim of this study was to verify the feasibility and usefulness of
      the internal jugular vein collapsibility index (IJV-CI) as an adjunct to the
      inferior vena cava collapsibility index (IVC-CI) to predict fluid responsiveness
      in spontaneously-breathing patients with sepsis. METHODS: Three stages of
      sonographic scanning were performed. Hemodynamic data were collected using the
      Ultrasonic Cardiac Output Monitor 1A system (Uscom, Ltd., Sydney, NSW, Australia)
      coupled with paired assessments of IVC-CI and IJV-CI at baseline, after passive
      leg raise (PLR), and again in semi-recumbent position. Fluid responsiveness was
      assessed according to changes in the cardiac index (CI) induced by PLR. Patients
      were retrospectively divided into 2 groups: fluid responder if an increase in CI
      (DeltaCI) >=15% was obtained after PLR maneuver, and non-responder if DeltaCI was
      <15%. RESULTS: Total of 132 paired scans of IJV and IVC were completed in 44
      patients who presented with sepsis and who were not receiving mechanical
      ventilation (mean age: 54.6+/-16.1 years). Of these, 23 (52.2%) were considered
      to be responders. Responders had higher IJV-CI and IVC-CI before PLR maneuver
      than non-responders (p<0.001). IJV-CI of more than 36% before PLR maneuver had
      78% sensitivity and 85% specificity to predict responder. Furthermore, less time
      was needed to measure venous diameters for IJV-CI (30 seconds) compared with IVC
      CI (77.5 seconds; p<0.001). CONCLUSION: IJV-CI is a precise, easily acquired, non
      invasive parameter of fluid responsiveness in patients with sepsis who are not
      mechanically ventilated, and it appears to be a reasonable adjunct to IVC-CI.

PMID- 28762450
TI  - Prognostic factors in acute mesenteric ischemia and evaluation with Mannheim
      Peritonitis Index and platelet-to-lymphocyte ratio.
AB  - BACKGROUND: Acute mesenteric ischemia (AMI) is a disease that has a very high
      mortality rate and for which the diagnosis is frequently delayed. The aim of the
      present study was to assess the predictive value of the Mannheim Peritonitis
      Index (MPI) and platelet-to-lymphocyte (P/L) ratio in the prognosis of AMI.
      METHODS: The files of 34 patients diagnosed with AMI between September 2014 and
      April 2016 were retrospectively examined. The patients were divided into 2 groups
      based on survival. The parameters of MPI and P/L ratio, demographic data, and
      duration of hospitalization were recorded and compared. RESULTS: In all, 19
      (55.9%) patients were male, and 15 (44.1%) were female. Total of 19 patients
      (55.9%) were discharged with a complete recovery, while 15 (44.1%) died. MPI mean
      value was 21.13+/-7.55 and 16.00+/-5.24 in those who died and survived,
      respectively (p=0.026). P/L ratio was 288.48+/-233.01 and 373.82+/-389.62 in
      those who survived and died, respectively (p=0.045). CONCLUSION: MPI and P/L
      ratio are simple and reliable methods to predict the prognosis of AMI.

PMID- 28762451
TI  - Esophageal button battery ingestion in children.
AB  - BACKGROUND: Button battery lodged in the esophagus carries a high risk of
      morbidity and mortality. The purpose of this study was to present cases of
      patients with esophageal button battery ingestion treated at our clinic and to
      emphasize the importance of early diagnosis and treatment. METHODS: Records of
      patients admitted to our hospital for foreign body ingestion between January 2010
      and May 2015 were retrospectively reviewed. Cases with button battery lodged in
      the esophagus were included in the study. Patient data regarding age, sex, length
      of time after ingestion until admission, presenting clinical symptoms, type and
      localization of the battery, management, and prognosis were analyzed. RESULTS:
      Among 1891 foreign body ingestions, 71 were localized in the esophagus, and 8 of
      those (11.2%) were cases of button battery ingestion. Mean age was 1.7 years.
      Admission was within 6 hours of ingestion in 5 cases, after 24 hours had elapsed
      in 2, and 1 month after ingestion in 1 case. All patients but 1 knew the history
      of ingestion. Prompt endoscopic removal was performed for all patients. Three
      patients developed esophageal stricture, which responded to dilatation.
      CONCLUSION: Early recognition and timely endoscopic removal is mandatory in
      esophageal button battery ingestion. It should be suspected in the differential
      diagnosis of patients with persistent respiratory and gastrointestinal symptoms.

PMID- 28762452
TI  - Eight years of clinical experience with digit replantation: Demographic
      characteristics and outcomes.
AB  - BACKGROUND: Despite surgical and technical advances in microsurgery, it is still
      difficult to obtain satisfactory results after replantation of finger amputation.
      The aim of the present study was to discuss some of the many factors that can
      affect the success rate of replantation. METHODS: A retrospective analysis of 60
      patients with 85 finger replantations was performed. Revascularizations and
      replantations proximal to the metacarpophalangeal joint were excluded.
      Demographic characteristics of the patients, place of injury, mechanism of
      injury, level of amputation, and success rate were examined. RESULTS: A total of
      53 male and 7 female patients with mean age of 31 years were included in the
      study. Index finger (27%) was the most commonly replanted digit. Left side was
      the more affected, with 62%. Mechanism of injury was crush in 56%, guillotine in
      23%, and avulsion in 21% of replanted digits. Success rate was 81%, 53%, and 36%
      in guillotine, crush, and avulsion injuries, respectively. CONCLUSION: In
      conclusion, the injury type and personal variables are very important in the rate
      of replantation success. Knowledge about the effects of different factors on the
      results of replantation surgery will provide guidance to hand surgeons in order
      to inform patients and their relatives properly.

PMID- 28762453
TI  - Damage control surgery: 6 years of experience at a level I trauma center.
AB  - BACKGROUND: Damage control surgery (DCS) has been a well-established practice in
      the management of trauma victims for more than 2 decades now. The primary aim of
      this study was to review and analyze the presentation and outcome of patients
      with torso trauma who underwent DCS at Level I trauma center. METHODS:
      Retrospective study was conducted using database records prospectively maintained
      over period of 6 years from 2008 through 2013 at an urban Level I trauma center.
      Data available from hospital medical records were analyzed to study presentation,
      mechanism of injury, organs injured, associated injuries, and outcome in patients
      who underwent DCS following torso trauma. Primary outcome measure was survival.
      RESULTS: Total of 61 patients were identified who had undergone DCS during the
      study period. Majority of these patients were males (n=59), had sustained blunt
      trauma as result of road traffic injury, and had presented with shock (n=49). The
      30-day mortality rate was 54%. Mortality was significantly associated with shock
      (63% cases died; p=0.008), and with Glasgow Coma scale <=8 (85% died; p=0.001).
      Injuries significantly associated with high mortality were hepatic injury (n=15;
      11 died), major vascular injury (n=10; 3 died), cardiac injury (n=5; 3 died), and
      pelvic fracture (n=17; 10 died). Re-exploration was required in 28 cases with 13
      deaths. Mesh laparostomy was performed in 24 cases, with mortality in 58%.
      CONCLUSION: In the absence of more effective alternative, especially at
      facilities with limited resources, DCS may be appropriate in critically injured
      patients; however, it continues to be associated with significant morbidity and
      high mortality, even at tertiary care centers.

PMID- 28762454
TI  - Use of trauma scoring systems to determine the physician's responsibility in
      cases of traumatic death with medical malpractice claim.
AB  - BACKGROUND: Traumatic injury is near the top of World Health Organization list of
      leading causes of death, and one of the major factors affecting mortality is the
      severity of the trauma. During medical intervention for trauma patients, some
      injuries may be overlooked, and this misstep may be the basis of a malpractice
      claim. The objective of this study was to provide a new approach to evaluating
      medical malpractice cases by discussing the benefits of the use of trauma scores.
      METHODS: Cases of alleged malpractice that were discussed and concluded between
      2010 and 2013 were selected from the case archive of the General Committee of the
      Council of Forensic Medicine (GC of CFM). Injury severity scores were calculated
      from the medical records of accused physicians and from the autopsy or final
      clinical evaluation records and compared. RESULTS: Between the years 2010 and
      2013, 263 cases of alleged medical malpractice were discussed and concluded by
      the general committee. Of these, in 25 cases of patient death, the reason for
      admission to the hospital was traumatic injury. Various surgical specialties were
      involved. In these 25 cases, 34 physicians were accused of medical malpractice,
      and the General Committee classified the interventions of 14 physicians in 12
      cases as "malpractice." Missed injuries and unrecognized diagnoses can be
      established by comparing the Injury Severity Score and New Injury Severity Score
      values in the findings of accused physicians with the subsequent findings of last
      evaluation or autopsy. CONCLUSION: In a medical malpractice case, calculating
      injury severity scores may assist an expert witness or judge to detect any unseen
      injuries and to determine the likely survival potential of the patient, but these
      values do not provide enough information to evaluate all of the evidence or draw
      conclusions about the entire case. All contributing factors to trauma severity
      should be considered along with the trauma score and other case factors.

PMID- 28762455
TI  - Ischemia-modified albumin and other inflammatory markers in the diagnosis of
      appendicitis in children.
AB  - BACKGROUND: The aim of the present study was to determine relationship of
      ischemia-modified albumin (IMA) level, C-reactive protein (CRP) level,
      erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, neutrophil-to
      lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet
      volume (MPV) to appendicitis in children. METHODS: Study included total of 63
      patients who presented at hospital between May 2015 and November 2015. Of these,
      30 were cases of appendicitis, and 33 were healthy control subjects. The groups
      were statistically similar in age and gender. RESULTS: Receiver operating
      characteristic curve was evaluated for IMA, CRP, ESR, WBC, MPV, NLR, and PLR
      values in patients with appendicitis, and IMA was determined to have highest area
      under the curve value (0.991), followed by NLR (0.946), CRP (0.808), PLR (0.779),
      ESR (0.767), WBC (0.749), and MPV (0.583). CONCLUSION: Use of NLR, PLR, IMA, and
      ESR values may be helpful in diagnosis of appendicitis, in addition to WBC and
      CRP values, lower right quadrant abdominal pain, and ultrasonography signs
      commonly used.

PMID- 28762456
TI  - Total hip arthroplasty for acetabular fractures: "Early Application".
AB  - BACKGROUND: The aim of this study was to evaluate the functional and clinical
      results of early total hip arthroplasty performed to treat acetabulum fracture.
      METHODS: Evaluation of 17 patients who were diagnosed with acetabulum fracture
      and treated with early total hip arthroplasty between January 2008 and October
      2013 was performed. In all, 14 patients were male, and 3 were female, with mean
      age of 52 years (range: 29-80 years). Time elapsed between trauma and operation
      was mean of 13 days (range: 2-21 days). Observation period was average of 48.2
      months (range: 24-70 months). Mean Harris Hip Score was 89.6 (range: 70-100).
      RESULTS: In 13 patients, score was good or excellent. Total of 7 of 10 patients
      had returned to their pre-trauma jobs. Mean length of time for return to work was
      determined to be 7.2 months (range: 1.5-24 months). Of the total, 9 (52.9%)
      patients were diagnosed with heterotopic ossification according to Brooker
      Classification. CONCLUSION: After acetabulum fracture, early total hip
      arthroplasty with the correct indications and appropriate patient can result in
      functional, pain-free hip joint with the advantages of early mobilization, early
      return to work, and decrease in reoperation risk. Heterotopic ossification
      prophylaxis should be considered in the presence of 1 or more risk factors, such
      as a head injury, high-energy trauma, or associated musculoskeletal injuries.

PMID- 28762457
TI  - Is intact fibula a disadvantage in treatment of tibial diaphysis fracture with
      intramedullary nailing?
AB  - BACKGROUND: The aim of this study was to compare solitary tibial diaphysis
      fractures and tibial diaphysis fractures associated with fibula fracture treated
      with the intramedullary nailing method. METHODS: Records of 254 patients
      diagnosed with tibial diaphysis fracture and treated with intramedullary nailing
      between 2010 and 2013 were examined and 30 patients were included in the study.
      Group 1 comprised patients with solitary tibial diaphysis fracture, and Group 2
      was made up of patients with tibial diaphysis fractures associated with fibula
      fracture. Patients in both groups were compared in terms of time to surgery,
      duration of surgical tourniquet, time to union, and varus, valgus, recurvatum,
      and antecurvatum deformities of the tibia at final follow-up. RESULTS: No
      statistically significant difference was found between the 2 groups in time to
      surgery, duration of surgical tourniquet, time to union, or varus, valgus,
      recurvatum, and antecurvatum deformities. CONCLUSION: Results indicated that
      intact fibula in tibial diaphysis fracture treated with intramedullary nailing
      was not a disadvantage; it did not affect rate of union or lead to loss of
      reduction, non-union, or malunion.

PMID- 28762458
TI  - Removal of cardiothoracic war-related shrapnel using video-assisted thoracoscopic
      surgery.
AB  - This is the first report in the literature to describe removing war-related
      cardiothoracic shrapnel using video-assisted thoracoscopic surgery (VATS). War
      blast caused penetrating thoracic and extremity injuries in 30-year-old man. He
      was referred to our hospital after stabilization. Magnetic resonance imaging was
      required to evaluate brachial plexus injury. Large, penetrating shrapnel fragment
      in the right posterior chest wall, retained shrapnel in apex of the right lung,
      and another fragment in the pericardium were removed using VATS in staged
      approach. Postoperative period was uneventful. VATS is useful in managing
      complex, war-related cardiothoracic injuries.

PMID- 28762459
TI  - A rare cause of hemoperitoneum: A case report of ruptured ileocolic artery
      aneurysm.
AB  - Visceral artery aneurysm (VAA) is very rare among vascular pathologies. Incidence
      reported in autopsy series and angiographic studies varies between 0.1% and 0.2%.
      Most cases are asymptomatic and are diagnosed as result of complications, or
      incidentally, when imaging is performed for another reason. Three percent of VAAs
      are superior mesenteric artery (SMA) terminal branch aneurysms. Intra- and/or
      extraperitoneal bleeding due to ruptured aneurysm is life-threatening condition
      and requires emergent intervention. Therefore, surgical or endovascular
      interventional treatment must be performed rapidly after diagnosis. Presently
      described is case of ileocolic artery aneurysm in a patient admitted with
      abdominal pain, nausea, and vomiting. Endovascular intervention had been planned;
      however, during hospitalization, aneurysm ruptured and emergent surgery was
      performed. Review of the literature is also presented.

PMID- 28762460
TI  - Successful endoscopic treatment of an unusual foreign body in the stomach: A
      package of heroin.
AB  - Drug addiction is an important medical and social problem. "Body packing" is
      frequently used for concealed transportation of illegal drugs. The drug is packed
      in small plastic packages and swallowed or placed into body cavities, such as the
      rectum or the vagina. Another aspect is "body stuffing," in which the drug
      package is usually hastily swallowed in order to avoid arrest. Presently
      described is case of a body stuffer who ingested a package of heroin and was
      successfully treated with upper gastrointestinal endoscopy. Upper
      gastrointestinal endoscopy is a safe alternative therapeutic option in body
      stuffers in selected cases.

PMID- 28762461
TI  - Cordycepin prevents postoperative formation of intra-abdominal adhesion in a rat
      model: An experimental study.
AB  - BACKGROUND: The aim of the present study was to investigate whether cordycepin
      prevented adhesion formation in a rat model. METHODS: Rats were randomly assigned
      to 3 groups of 10 rats. CONTROL GROUP: The absence of adhesion was confirmed via
      laparotomy. Adhesion group: The cecum was removed from the abdomen and scraped
      with a dry gauze bandage until petechial hemorrhagic foci developed. Cordycepin
      group: The same surgical procedure was performed as in the adhesion group, and 10
      mg/kg cordycepin was administered intraperitoneally. After 15 days, the rats were
      sacrificed humanely via cardiac blood withdrawal under anesthesia. The rats were
      then analyzed morphologically and histopathologically, and hydroxyproline (OH-p)
      and malondialdehyde (MDA) levels were measured. RESULTS: Macroscopic analysis
      revealed significantly less adhesion in the cordycepin group than in the adhesion
      group (p<0.01). Furthermore, significant histopathological improvement was also
      evident in the cordycepin group compared to the adhesion group (p<0.05). The
      levels of OH-p and MDA in blood and tissue were higher in the adhesion group than
      in the control group, and lower in the cordycepin group than the adhesion group.
      Interestingly, MDA level was significantly lower (blood: p<0.05; tissue: p<0.01)
      in the cordycepin group than in the adhesion group, whereas only tissue OH-p was
      significantly lower in the cordycepin group compared with the adhesion group
      (p<0.05). One rat in both adhesion group and cordycepin group died
      postoperatively. CONCLUSION: Results indicated that cordycepin effectively
      reduced adhesion in a rat abrasion model. Thus, this agent may be valuable to
      prevent postoperative adhesion.

PMID- 28762462
TI  - Radiation-induced neurocognitive dysfunction in head and neck cancer patients.
AB  - It might seem odd that a special issue about Gianni Bonadonna would publish a
      review on radiation-induced neurocognitive dysfunction. Dr. Gianni Bonadonna is
      considered a pioneer in medical oncology history, mainly due to new and
      revolutionary treatment approaches proposed in breast cancer and Hodgkin
      lymphoma. He had an active role in the field of medical oncology, especially
      through lectures and textbooks. He shared his considerable insight of
      understanding cancer behavior and evaluating research advances over the years to
      prevent tumor recurrence and preserve patients from unnecessary toxicity. From a
      theoretical point of view, this complex vision is valid for all malignancies and
      can be indirectly shifted to every primary cancer, including head and neck cancer
      (HNC). During the last decades, multidisciplinary treatment for HNC has improved
      clinical outcomes but makes acute and late toxicity challenging. This article
      highlights the main central nervous structures that have a major impact on the
      development of neurocognitive dysfunction after radiotherapy for HNC. We briefly
      summarize the specific structure contouring instructions and the dose-volume
      histogram parameters. The aim is to raise awareness in clinicians in defining
      normal tissues to optimize radiotherapy regimens.

PMID- 28762463
TI  - Crystalglobulinaemia: Multiple myeloma presenting with cutaneous and neurological
      manifestations.

PMID- 28762464
TI  - The mid-point transverse process to pleura (MTP) block: a new end-point for
      thoracic paravertebral block.
AB  - Current descriptions of thoracic paravertebral block techniques require the
      needle tip to be anterior to the superior costotransverse ligament. We
      hypothesised that an injection point midway between the posterior border of the
      transverse process and the pleura would result in spread to the paravertebral
      space. We completed bilateral injections of 5 ml methylene blue 0.2% midway
      between the posterior border of the transverse process and the pleura at T2, T4,
      T6, T8 and T10 in three unembalmed cadavers. The presence of methylene blue dye
      at the nerve root in the paravertebral space, the corresponding intercostal nerve
      and sympathetic chain at the level of injection, and at additional levels, was
      examined. We identified the superior costotransverse ligament, pleural
      displacement and spread to the erector spinae plane. We describe two case reports
      using this technique in patients. Our cadaver results and clinical cases
      demonstrate that, with the exception of cadaver 1, an injection point midway
      between the posterior border of the transverse process and pleura consistently
      achieved spread of dye at least to the paravertebral space at the level of
      injection, and frequently to adjacent levels. This may be a plausible explanation
      for the landmark technique's inability to reliably achieve a multilevel block. We
      describe a new ultrasound-guided technique for a single level paravertebral
      block.

PMID- 28762465
TI  - Linagliptin-induced bullous pemphigoid.

PMID- 28762466
TI  - Using immune checkpoint inhibitors without exacerbation in a melanoma patient
      with pemphigus foliaceus.

PMID- 28762468
TI  - Comparison of three embedding media for preparation of frozen sections for Mohs
      micrographic surgery.

PMID- 28762467
TI  - Sulfasalazine-Induced Agranulocytosis Is Associated With the Human Leukocyte
      Antigen Locus.
AB  - Agranulocytosis is a serious, although rare, adverse reaction to sulfasalazine,
      which is used to treat inflammatory joint and bowel disease. We performed a
      genome-wide association study comprising 9,380,034 polymorphisms and 180 HLA
      alleles in 36 cases of sulfasalazine-induced agranulocytosis and 5,170 population
      controls. Sulfasalazine-induced agranulocytosis was significantly associated with
      the HLA region on chromosome 6. The top hit (rs9266634) was located close to HLA
      B, odds ratio (OR) 5.36 (95% confidence interval (CI) (2.97, 9.69) P = 2.55 * 10
      8 ). We HLA-sequenced a second cohort consisting of 40 cases and 142 treated
      controls, and confirmed significant associations with HLA-B*08:01, OR = 2.25 (95%
      CI (1.02, 4.97) P = 0.0439), in particular the HLA-B*08:01 haplotype HLA
      DQB1*02:01-DRB1*03:01-B*08:01-C*07:01, OR = 3.79 (95% CI (1.63, 8.80) P =
      0.0019), and with HLA-A*31:01, OR = 4.81 (95% CI (1.52, 15.26) P = 0.0077). The
      number needed to test for HLA-B*08:01 and HLA-A*31:01 to avoid one case was
      estimated to be 1,500. We suggest that intensified monitoring or alternative
      treatment should be considered for known carriers of HLA-B*08:01 or HLA-A*31:01.

PMID- 28762470
TI  - Cutaneous lymphangiectasia in a patient with primary intestinal lymphangiectasia.

PMID- 28762469
TI  - Impairment of GABAergic system contributes to epileptogenesis in glutaric
      acidemia type I.
AB  - OBJECTIVES: Glutaric acidemia type I (GA-I) is an inherited neurometabolic
      disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCDH) and
      characterized by increased levels of glutaric, 3-OH-glutaric, and glutaconic
      acids in the brain parenchyma. The increment of these organic acids inhibits
      glutamate decarboxylase (GAD) and consequently lowers the gamma-aminobutyric acid
      (GABA) synthesis. Untreated patients exhibit severe neurologic deficits during
      development, including epilepsy, especially following an acute encephalopathy
      outbreak. In this work, we evaluated the role of the GABAergic system on
      epileptogenesis in GA-I using the Gcdh-/- mice exposed to a high lysine diet
      (Gcdh-/- -Lys). METHODS: Spontaneous recurrent seizures (SRS), seizure
      susceptibility, and changes in brain oscillations were evaluated by video
      electroencephalography (EEG). Cortical GABAergic synaptic transmission was
      evaluated using electrophysiologic and neurochemical approaches. RESULTS: SRS
      were observed in 72% of Gcdh-/- -Lys mice, whereas no seizures were detected in
      age-matched controls (Gcdh+/+ or Gcdh-/- receiving normal diet). The severity and
      number of PTZ-induced seizures were higher in Gcdh-/- -Lys mice. EEG spectral
      analysis showed a significant decrease in theta and gamma oscillations and
      predominant delta waves in Gcdh-/- -Lys mice, associated with increased EEG left
      index. Analysis of cortical synaptosomes revealed a significantly increased
      percentage of glutamate release and decreased GABA release in Gcdh-/- -Lys mice
      that were associated with a decrease in cortical GAD immunocontent and activity
      and confirmed by reduced frequency of inhibitory events in cortical pyramidal
      cells. SIGNIFICANCE: Using an experimental model with a phenotype similar to that
      of GA-I in humans-the Gcdh-/- mice under high lysine diet (Gcdh-/- -Lys)-we
      provide evidence that a reduction in cortical inhibition of Gcdh-/- -Lys mice,
      probably induced by GAD dysfunction, leads to hyperexcitability and increased
      slow oscillations associated with neurologic abnormalities in GA-I. Our findings
      offer a new perspective on the pathophysiology of brain damage in GA-I.

PMID- 28762471
TI  - Clinical presentation of terbinafine-induced severe liver injury and the value of
      laboratory monitoring: a Critically Appraised Topic.
AB  - CONTEXT: Many physicians monitor liver function tests during terbinafine therapy.
      OBJECTIVES: To evaluate the symptoms of published cases of terbinafine-associated
      severe drug-induced liver injury (DILI) to assess the utility of laboratory
      monitoring. DATA SOURCES: We based our search on the LiverTox database of the
      National Institutes of Health, but we also searched both PubMed and Embase. In
      addition, we hand searched the references of the papers we found. STUDY
      SELECTION: All reports of patients with DILI on terbinafine and with reported
      clinical symptoms, or absence thereof, were evaluated. DATA EXTRACTION: Two
      independent reviewers (J.A. and O.N.K.) assessed articles for eligibility of
      inclusion, and collected and evaluated the data. DATA SYNTHESIS: Thirty-eight
      papers fulfilled the inclusion criteria, with reports of 69 symptomatic patients.
      The mean duration of terbinafine treatment until onset of symptoms was 30.2 days
      (range 5-84). Symptoms in order of frequency were jaundice, flu-like symptoms,
      dark urine and pruritus. Patients experienced symptoms for a mean and median of
      14.8 and 16 days, respectively (range 0-42) until seeking medical attention.
      CONCLUSIONS: Patients who had DILI were symptomatic, usually with jaundice,
      abdominal pain and general malaise, but also with severe pruritus. No
      asymptomatic patient was identified through laboratory screening. The timeline of
      DILI onset varies significantly, but most cases occur between 4 and 6 weeks.
      There was no time point at which monitoring was meaningful, and we do not
      recommend monitoring of liver function tests on terbinafine; however, patients
      should be advised to discontinue treatment and look for medical care when
      symptoms of DILI occur.

PMID- 28762472
TI  - Absence of Notch1 in murine myeloid cells attenuates the development of
      experimental autoimmune encephalomyelitis by affecting Th1 and Th17 priming.
AB  - Inhibition of Notch signalling in T cells attenuates the development of
      experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple
      sclerosis. Growing evidence indicates that myeloid cells are also key players in
      autoimmune processes. Thus, the present study evaluates the role of the Notch1
      receptor in myeloid cells on the progression of myelin oligodendrocyte
      glycoprotein (MOG)35-55 -induced EAE, using mice with a myeloid-specific deletion
      of the Notch1 gene (MyeNotch1KO). We found that EAE progression was less severe
      in the absence of Notch1 in myeloid cells. Thus, histopathological analysis
      revealed reduced pathology in the spinal cord of MyeNotch1KO mice, with decreased
      microglia/astrocyte activation, demyelination and infiltration of CD4+ T cells.
      Moreover, these mice showed lower Th1 and Th17 cell infiltration and expression
      of IFN-gamma and IL-17 mRNA in the spinal cord. Accordingly, splenocytes from
      MyeNotch1KO mice reactivated in vitro presented reduced Th1 and Th17 activation,
      and lower expression of IL-12, IL-23, TNF-alpha, IL-6, and CD86. Moreover,
      reactivated wild-type splenocytes showed increased Notch1 expression, arguing for
      a specific involvement of this receptor in autoimmune T cell activation in
      secondary lymphoid tissues. In summary, our results reveal a key role of the
      Notch1 receptor in myeloid cells for the initiation and progression of EAE.

PMID- 28762473
TI  - Late diagnosis and atypical brain imaging of Aicardi-Goutieres syndrome: are we
      failing to diagnose Aicardi-Goutieres syndrome-2?
AB  - : Aicardi-Goutieres syndrome (AGS) is a rare disorder with in utero or postnatal
      onset of encephalopathy and progressive neurological deterioration. The seven
      genetic subtypes of AGS are associated with abnormal type I interferon-mediated
      innate immune response. Most patients with AGS present with progressive
      microcephaly, spasticity, and cognitive impairment. Some, especially those with
      type 2 (AGS2), manifest milder phenotypes, reduced childhood mortality, and
      relative preservation of physical and cognitive abilities. In this report, we
      describe two siblings (sister and brother) diagnosed with AGS2 in their second
      decade, who exhibited static encephalopathy since 1 year of age with spastic
      quadriplegia and anarthria but preserved intellect. Both were homozygous for the
      common pathogenic RNASEH2B allele (c.529G>A, p.Ala177Thr). Rather than
      manifesting calcifications and leukoencephalopathy, both had increased iron
      signal in the basal ganglia. Our report broadens the clinical and imaging
      spectrum of AGS2 and emphasizes the importance of including AGS2 in the
      differential diagnosis of idiopathic spastic cerebral palsy. WHAT THIS PAPER
      ADDS: We identified two siblings (sister and brother) with atypical Aicardi
      Goutieres syndrome type 2 due to RNASEH2B mutation. Manifestations included
      spastic quadriplegia and anarthria but preserved intellect and increased iron
      signal in the basal ganglia. RNASEH2B-related Aicardi-Goutieres syndrome type 2
      can have present with a variable phenotype, including idiopathic spastic cerebral
      palsy.

PMID- 28762474
TI  - Adipokines, psoriasis, systemic inflammation, and endothelial dysfunction.
AB  - Adipokines are secreted by white adipose tissue, an active endocrine organ, and
      play a role in the regulation of metabolic functions such as lipid metabolism,
      inflammation, and vascular homeostasis. Adipokines are secreted in excess in
      obesity and contribute to the development of associated comorbidities such as
      metabolic syndrome and atherosclerosis. Psoriasis, a chronic immune-mediated skin
      disease, is associated with obesity and increased cardiovascular risk.
      Understanding the role of adipokines in psoriasis may in part explain the
      association between psoriasis and cardiovascular disease. This review summarizes
      the data regarding key adipokines in patients with psoriasis and the change in
      adipokine profiles with psoriasis therapy. Adipokines may be mediators of
      cutaneous inflammation suggesting a role in the pathophysiology of psoriasis and
      the development of comorbidities.

PMID- 28762476
TI  - Use of Early Clinical Trial Data to Support Thorough QT Study Waiver for
      Upadacitinib and Utility of Food Effect to Demonstrate ECG Assay Sensitivity.
AB  - Exposure-response analyses of QT data from early-stage clinical studies represent
      a valuable tool to assess the QT prolongation potential for drugs in development
      in lieu of standalone thorough QT (TQT) studies. However, demonstrating adequate
      electrocardiogram assay sensitivity can be challenging in the absence of a
      positive pharmacological control. Upadacitinib is a Janus kinase 1 inhibitor
      currently being evaluated in phase III rheumatoid arthritis trials. Exposure
      response analyses to evaluate the QT prolongation potential for upadacitinib from
      phase I trials and the utility of the effect of food on QTcF to demonstrate ECG
      assay sensitivity are presented. The analyses demonstrated no effect of
      upadacitinib on QT interval and confirmed the sensitivity of the ECG assay to
      detect the small QT shortening effect caused by food. Lack of bias from manual
      ECG adjudication was also demonstrated. These analyses supported requesting a
      waiver for the regulatory requirement for a dedicated thorough QT study for
      upadacitinib.

PMID- 28762475
TI  - Behavioral and fMRI responses to fearful faces are altered in benign childhood
      epilepsy with centrotemporal spikes (BCECTS).
AB  - OBJECTIVE: We hypothesized that children with benign childhood epilepsy with
      centrotemporal spikes (BCECTS) might have altered social cognitive skills and
      underlying neural networks. METHODS: We studied 13 patients with BCECTS and 11
      age-matched controls using event-related functional magnetic resonance imaging
      (fMRI) with an emotional discrimination task consisting of viewing happy,
      fearful, scrambled, and neutral faces. Behavioral performance measured during the
      task was correlated with clinical variables and behavioral ratings. RESULTS: In
      comparison with age-matched controls, children with BCECTS performing a fearful
      faces detection task showed significantly reduced bilateral fMRI activation in
      the insular cortex, caudate, and lentiform nuclei, as well as increased response
      time. The percentage of errors made by children with BCECTS correlated negatively
      with age, a finding not observed in controls. In patients, accuracy positively
      correlated with time since the last seizure. The above abnormalities were not
      observed during happy faces detection task, except for a slower response in
      children with BCECTS as compared to controls. SIGNIFICANCE: Our study suggests
      that BCECTS is associated with altered social cognition network and function,
      particularly for the identification of fearful faces. The age dependency of some
      of these findings supports the view that a delayed maturation of spiking cortical
      regions might underlie the cognitive dysfunction observed in BCECTS.

PMID- 28762477
TI  - Mosaic intragenic deletion of FBN2 and severe congenital contractural
      arachnodactyly.

PMID- 28762478
TI  - Is the prevalence of hidradenitis suppurativa being overestimated in Europe? Or
      is the disease underdiagnosed? Evidence from a nationwide study across Portuguese
      public hospitals.

PMID- 28762480
TI  - Do pictures say a thousand words: Email referrals for dermatology advice at
      Waikato Hospital.

PMID- 28762479
TI  - Brentuximab vedotin in CD30+ primary cutaneous T-cell lymphomas: a review and
      analysis of existing data.
AB  - BACKGROUND: The utility of brentuximab vedotin (BV) in CD30+ systemic lymphomas
      is established, however evidence for treating primary cutaneous lymphoma remains
      limited. This study aimed to evaluate BV in treating CD30+ transformed mycosis
      fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (PC-ALCL).
      METHODS: A literature review was conducted, and we analyzed data from published
      trials and case reports obtained via search of Ovid-MEDLINE(r) and PubMed
      databases. The search yielded 372 reports, and 10 publications met inclusion
      criteria. Sixty-one patients with CD30+ transformed MF and seven with PC-ALCL
      were included. RESULTS: Mean age at BV initiation was 60.8 years (67 - PC-ALCL;
      60.1 - MF), and 4.1 therapies were attempted prior to BV (3.1 - PC-ALCL; 4.2 -
      MF). The overall response rate was 67.7% (100% - PC-ALCL; 63.9% - MF), with 16.2%
      of patients experiencing complete response (100% - PC-ALCL; 6.6% - MF). Mean time
      to clinical response was 5.3 and 9.3 weeks for PC-ALCL and MF, respectively. Mean
      response duration for patients with PC-ALCL was 7.6 and 7.8 months for MF.
      Peripheral neuropathy (57.2%) and fatigue (35.6%) were the most commonly reported
      adverse effects. CONCLUSIONS: This analysis summates the current evidence
      regarding the use of BV in treating CD30+ MF and PC-ALCL. Preliminary results
      indicate that BV is effective for CD30+ CTCL, however additional studies with
      larger sample sizes are necessary. The study provides clinicians with the
      clinical context in which BV may be appropriate as well as information regarding
      therapeutic expectations and outcomes.

PMID- 28762481
TI  - Unwanted lentigines after topical tacrolimus for vitiligo.

PMID- 28762482
TI  - Medication adherence among patients with psoriasis on traditional systemic and
      biologics treatment.

PMID- 28762483
TI  - High-Dimensional Single-Cell Analysis with Mass Cytometry.
AB  - Mass cytometry is an analytical technology that combines the sample preparation
      workflow typical of flow cytometry and the detection capacity of atomic mass
      spectroscopy, allowing for highly multiplexed measurements of protein or nucleic
      acid targets on single cells. In 2014, the mass cytometer was adapted for the
      acquisition of samples from microscopy slides (termed imaging mass cytometry),
      greatly increasing the applicability of this technology. By using antibodies (or
      other probes) labeled with purified metal isotopes, the mass cytometer is able to
      detect up to 50 different parameters (current practical limit) at the single-cell
      level, enabling a deep and thorough profiling of individual cells in terms of
      their cell surface protein phenotype, physiological state, proliferation
      potential, and many other cell states or features. (c) 2017 by John Wiley & Sons,
      Inc.

PMID- 28762484
TI  - Venipuncture Procedures: Sources of Human Peripheral Blood Cells, Serum, and
      Plasma.
AB  - Peripheral blood is the chief source of mononuclear cells (lymphocytes and
      monocytes) for immunologic studies of humans. This appendix presents protocols
      for obtaining blood by simple venipuncture when relatively small amounts of blood
      (10 to 100 ml) are necessary or by lymphapheresis when large amounts (300 to 5000
      ml) are necessary. Cells collected by these procedures can be further separated
      by techniques described in Chapter 7. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28762485
TI  - Characterization of Human Blood Monocytes and Intestinal Macrophages.
AB  - Monocytes and macrophages play fundamental roles in defense against microbes,
      clearance of senescent and dead cells, and immunoregulation. Although blood
      monocytes are the source of intestinal macrophages in the developed mucosal
      immune system, blood monocytes and intestinal macrophages from healthy human
      subjects display distinct phenotypic and functional differences. Blood monocytes
      can be induced to polarize into M1 and M2 macrophages, whereas intestinal
      macrophages appear to be terminally differentiated and are unable to undergo such
      inducible polarization. Nevertheless, in response to local conditions, monocytes
      differentiated into intestinal macrophages display phenotypic and functional
      characteristics that enhance their capacity to provide non-inflammatory host
      defense and participate in local immunoregulation. Using the protocols described
      here, this unit presents the key phenotypic and functional differences between
      human blood monocytes and intestinal macrophages, as well as between mouse and
      human intestinal macrophages. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28762486
TI  - Universal Precautions: Necessary Safety Procedures When Handling Human Blood,
      Body Fluids, and Specimens.
AB  - Universal precautions are observed whenever handling human blood, body fluids, or
      specimens as a means of preventing exposure to blood-borne pathogens. This
      appendix outlines safety procedures to follow whenever undertaking research
      activities that involve human blood, body fluids, and specimens. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 28762487
TI  - Nomenclature and Serology of HLA Class I and Class II Alleles.
AB  - This overview presents nomenclature and serology information on human leucocyte
      antigens, or HLA molecules, which are encoded by a cluster of genes linked on the
      short arm of chromosome 6. This region is known as the major histocompatibility
      complex and codes for class I and class II molecules, which are distinguished
      from each other based upon their structure, tissue distribution, and source of
      peptide antigen, as well as upon their interactions with T cell subsets. (c) 2017
      by John Wiley & Sons, Inc.

PMID- 28762488
TI  - A Real-Time Cytotoxicity Assay as an Alternative to the Standard Chromium-51
      Release Assay for Measurement of Human NK and T Cell Cytotoxic Activity.
AB  - This unit describes the monitoring and quantification of cellular cytotoxicity
      using a non-radioactive and real-time cytotoxic assay. The extent of target-cell
      lysis is monitored over time by imaging and quantifying live fluorescent target
      cells using a cell-imaging multimode reader. This assay is performed in a 96 well
      plate in optimized culture conditions at 37 degrees C in the presence of 5% CO2 .
      The basic protocol describes natural killer cell-mediated cytotoxic assay that
      can be adapted to include antibodies blocking inhibitory NK receptors or
      triggering antibody-dependent cell-mediated cytotoxicity (ADCC). The assay is
      also suitable for antigen specific T-cell cytotoxic assays. Until now, the
      standard chromium 51 (51 Cr)-release assay has remained the sole sensitive assay
      but its major drawbacks include cost and hazard of handling radioactivity. The
      real-time cytotoxic assay is therefore an effective alternative providing a
      robust and sensitive assay that accurately monitors lysis of target cells over
      time. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28762489
TI  - The Universally Unrecognized Assumption in Predicting Drug Clearance and Organ
      Extraction Ratio.
AB  - For almost a half-century clearance concepts have been utilized in
      pharmacokinetics to understand the relationship between the dose administered and
      the time course of systemic concentrations to predict efficacy and safety, as
      well as how dosing should be modified in disease states. Various models of organ
      clearance/elimination have been proposed and tested. Surprisingly, however, the
      theoretical basis for the appropriate data collection to test these models has
      never been evaluated. Here we show that in vivo data collection limitations and
      the extraction ratio concept itself are only consistent with the well-stirred
      model of hepatic elimination. Evaluating measures of drug concentrations entering
      and leaving an organ will appear to best fit the well-stirred model, since
      driving force concentrations within the organ of elimination cannot be measured.

PMID- 28762491
TI  - Generation of Recombinant Vaccinia Viruses.
AB  - This unit describes how to infect cells with vaccinia virus and then transfect
      them with a plasmid-transfer vector or PCR fragment to generate a recombinant
      virus. Selection and screening methods used to isolate recombinant viruses and a
      method for the amplification of recombinant viruses are described. Finally, a
      method for live immunostaining that has been used primarily for detection of
      recombinant modified vaccinia virus Ankara (MVA) is presented. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 28762490
TI  - Site-Specific Protein Labeling via Sortase-Mediated Transpeptidation.
AB  - Strategies for site-specific protein modification are highly desirable for the
      construction of conjugates containing non-genetically-encoded functional groups.
      Ideally, these strategies should proceed under mild conditions, and be compatible
      with a wide range of protein targets and non-natural moieties. The
      transpeptidation reaction catalyzed by bacterial sortases is a prominent strategy
      for protein derivatization that possesses these features. Naturally occurring or
      engineered variants of sortase A from Staphylococcus aureus catalyze a ligation
      reaction between a five-amino-acid substrate motif (LPXTG) and oligoglycine
      nucleophiles. By pairing proteins and synthetic peptides that possess these
      ligation handles, it is possible to install modifications onto the protein N- or
      C-terminus in site-specific fashion. As described in this unit, the successful
      implementation of sortase-mediated labeling involves straightforward solid-phase
      synthesis and molecular biology techniques, and this method is compatible with
      proteins in solution or on the surface of live cells. (c) 2017 by John Wiley &
      Sons, Inc.

PMID- 28762492
TI  - Purification of Recombinant Human Tyrosinase from Insect Larvae Infected with the
      Baculovirus Vector.
AB  - The purification of an enzyme from insect larvae infected with a baculovirus
      vector is described. The enzyme tyrosinase is of biomedical importance and
      catalyzes the first rate-limiting steps in melanin production. Tyrosinase
      mutations can result in oculocutaneous albinism type 1 (OCA1), an inherited eye
      disease associated with decreased melanin pigment production and vision defects.
      To simplify expression and subsequent purification, the extracellular domain is
      expressed in insect cells, produced in Trichoplusia ni larvae, and purified using
      affinity and size-exclusion chromatography. The purified recombinant human
      tyrosinase is a soluble monomeric glycoprotein with an activity that mirrors the
      tyrosinase in vivo function. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28762493
TI  - Mass-Tag Labeling Using Acyl-PEG Exchange for the Determination of Endogenous
      Protein S-Fatty Acylation.
AB  - The covalent coupling of fatty acids to proteins provides an important mechanism
      of regulation in cells. In eukaryotes, cysteine fatty acylation (S-fatty
      acylation) has been shown to be critical for protein function in a variety of
      cellular pathways as well as microbial pathogenesis. While methods developed over
      the past decade have improved the detection and profiling of S-fatty acylation,
      these are hampered in their ability to characterize endogenous protein S-fatty
      acylation levels under physiological conditions. Furthermore, understanding the
      contribution of specific sites and levels of S-fatty acylation remains a major
      challenge. To evaluate S-fatty acylation of endogenous proteins as well as to
      determine the number of S-fatty acylation events, we developed the acyl-PEG
      exchange (APE) that utilizes cysteine-specific chemistry to exchange S-fatty
      acylation sites with mass-tags of defined size, which can be readily observed by
      western blotting. APE provides a readily accessible approach to investigate
      endogenous S-fatty acylation from any sample source, with high sensitivity and
      broad applicability that complements the current toolbox of methods for thioester
      based post-translational modifications. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28762494
TI  - Protein-Lipid Interaction by Fluorescence (PLIF) to Characterize and Screen for
      Inhibitors of Protein-Phosphoinositide Interactions.
AB  - Phosphoinositides are key signaling and regulatory phospholipids that mediate
      important pathophysiological processes. This is achieved through the interaction
      of their phosphorylated inositol head group with a wide range of protein domains.
      Therefore, being able to determine the phosphoinositide specificity for effector
      protein is essential to the understanding of its cellular function. This unit
      describes a novel method named Protein-Lipid Interaction by Fluorescence, or
      PLIF. PLIF is a fast, reliable and high throughput assay that allows
      determination of the phosphoinositide specificity of proteins, simultaneously
      providing relative affinities. In addition, PLIF is suitable for screening
      inhibitors of protein- phosphoinositide interaction, allowing identification of
      potential pharmacological compounds. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28762495
TI  - Preparation of Cell Cultures and Vaccinia Virus Stocks.
AB  - The culturing of cell lines used with vaccinia virus, both as monolayer and in
      suspension, is described. The preparation of chick embryo fibroblasts (CEF) is
      presented for use in the production of the highly attenuated and host range
      restricted modified vaccinia virus Ankara (MVA) strain of vaccinia virus.
      Protocols for the preparation, titration, and trypsinization of vaccinia virus
      stocks, as well as viral DNA preparation and virus purification methods are also
      included. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28762497
TI  - T cell-dependent antigen adjuvanted with DOTAP-CpG-B but not DOTAP-CpG-A induces
      robust germinal center responses and high affinity antibodies in mice.
AB  - The development of vaccines for infectious diseases for which we currently have
      none, including HIV, will likely require the use of adjuvants that strongly
      promote germinal center responses and somatic hypermutation to produce broadly
      neutralizing antibodies. Here we compared the outcome of immunization with the T
      cell dependent antigen, NP-conjugated to chicken gamma globulin (NP-CGG)
      adjuvanted with the toll-like receptor 9 (TLR9) ligands, CpG-A or CpG-B, alone or
      conjugated with the cationic lipid carrier, DOTAP. We provide evidence that only
      NP-CGG adjuvanted with DOTAP-CpG-B was an effective vaccine in mice resulting in
      robust germinal center responses, isotype switching and high affinity NP-specific
      antibodies. The effectiveness of DOTAP-CpG-B as an adjuvant was dependent on the
      expression of the TLR9 signaling adaptor MyD88 in immunized mice. These results
      indicate DOTAP-CpG-B but not DOTAP-CpG-A is an effective adjuvant for T cell
      dependent protein antigen-based vaccines.

PMID- 28762498
TI  - Accuracy of on-site tests to detect anemia during prenatal care.
AB  - BACKGROUND: Anemia is a substantial contributor to poor pregnancy outcomes in low
      and middle-income countries. Access to laboratory facilities is limited;
      therefore, on-site testing warrants attention. OBJECTIVES: To determine the
      accuracy of on-site tests to detect anemia in pregnancy. SEARCH STRATEGY:
      MEDLINE, Embase, Scopus, CINAHL, and Web of Science were searched from inception
      until March 2016, with no language restrictions, using the terms "pregnancy,"
      "an(a)emia," and "h(a)emoglobin." SELECTION CRITERIA: Studies that evaluated the
      diagnostic accuracy of on-site hemoglobin tests versus laboratory-based reference
      tests during pregnancy were included. DATA COLLECTION AND ANALYSIS: Study
      characteristics and true positive, true negative, false positive, and false
      negative rates were extracted. Sensitivity, specificity, likelihood ratios, and
      post-test probabilities were calculated. Anemia was defined as a hemoglobin level
      of less than 110 g/L. MAIN RESULTS: Ten studies (4239 participants) were
      assessed. Copper sulfate provided 97% sensitivity (95% confidence interval [CI]
      88%-100%) and 71% specificity (95% CI 55%-85%); the Sahli method provided 86%
      sensitivity (95% CI 75%-94%) and 83% specificity (95% CI 68%-93%); and HemoCue
      provided 85% sensitivity (95% CI 79%-90%) and 80% specificity (95% CI 76%-83%).
      CONCLUSIONS: Some on-site tests are accurate and should be made widely available
      to improve detection of anemia in pregnancy.

PMID- 28762499
TI  - Prospective study of the feasibility and effectiveness of a second-trimester
      quadruple test for Down syndrome in Thailand.
AB  - OBJECTIVE: To evaluate the feasibility and effectiveness of a quadruple test for
      Down syndrome in the second trimester of pregnancy in clinical settings in
      Thailand. METHODS: From October 2015 to September 2016, a prospective study was
      undertaken in 19 hospitals in Songkhla province, Thailand. Women with a singleton
      pregnancy of 14-18 weeks were enrolled and underwent the quadruple test. The risk
      cutoff value was set at 1:250. All women with a positive test (risk >=1:250) were
      offered amniocentesis. Women were followed up until delivery. RESULTS: Among 2375
      women, 206 (8.7%) had a positive quadruple test; 98 (47.6%) of these women
      voluntarily underwent amniocentesis. Overall, seven pregnancies were complicated
      with chromosomal abnormalities (2.9 cases in 1000), including four cases of Down
      syndrome (1.7 in 1000) and three of other abnormalities. The detection, false
      positive, and accuracy rates of the quadruple test for Down syndrome were 75.0%,
      8.6%, and 91.4%, respectively. CONCLUSION: The quadruple test was found to be a
      feasible and efficient method for screening for Down syndrome in the second
      trimester of pregnancy in a Thai clinical setting. The test should be performed
      for pregnant women before an invasive test for Down syndrome.

PMID- 28762500
TI  - Myology of the forelimb of Majungasaurus crenatissimus (Theropoda, Abelisauridae)
      and the morphological consequences of extreme limb reduction.
AB  - Forelimb reduction occurred independently in multiple lineages of theropod
      dinosaurs. Although tyrannosaurs are renowned for their tiny, two-fingered
      forelimbs, the degree of their reduction in length is surpassed by abelisaurids,
      which possess an unusual morphology distinct from that of other theropods. The
      forelimbs of abelisaurids are short but robust and exhibit numerous crests,
      tubercles, and scars that allow for inferences of muscle attachment sites.
      Phylogenetically based reconstructions of the musculature were used in
      combination with close examination of the osteology in the Malagasy abelisaurid
      Majungasaurus to create detailed muscle maps of the forelimbs, and patterns of
      the muscular and bony morphology were compared with those of extant tetrapods
      with reduced or vestigial limbs. The lever arms of muscles crossing the
      glenohumeral joint are shortened relative to the basal condition, reducing the
      torque of these muscles but increasing the excursion of the humerus. Fusion of
      the antebrachial muscles into a set of flexors and extensors is common in other
      tetrapods and occurred to some extent in Majungasaurus. However, the presence of
      tubercles on the antebrachial and manual elements of abelisaurids indicates that
      many of the individual distal muscles acting on the wrist and digits were
      retained. Majungasaurus shows some signs of the advanced stages of forelimb
      reduction preceding limb loss, while also exhibiting features suggesting that the
      forelimb was not completely functionless. The conformation of abelisaurid
      forelimb musculature was unique among theropods and further emphasizes the
      unusual morphology of the forelimbs in this clade.

PMID- 28762501
TI  - Award for distinguished contributions to psychophysiology: J. Richard Jennings.

PMID- 28762502
TI  - The incidence of surgical site dehiscence following full-thickness
      gastrointestinal biopsy in dogs and cats and associated risk factors.
AB  - OBJECTIVES: The objectives of this study were to: (1) document the incidence of
      surgical site dehiscence after full-thickness gastrointestinal biopsy in dogs and
      cats and (2) identify potential risk factors. METHODS: Data relating to dogs and
      cats undergoing full-thickness gastrointestinal biopsy were reviewed
      retrospectively following submission of a completed questionnaire by 12 referral
      institutions. Outcome measures were definite dehiscence, possible dehiscence
      (clinical records suggestive of dehiscence but not confirmed), suspected
      dehiscence (definite and possible combined) and death within 14 days. Logistic
      regression was planned for analysis of association of dehiscence with low
      preoperative serum albumin, biopsy through neoplastic tissue, biopsy alongside
      another major abdominal surgical procedure and biopsy of the colon. RESULTS: Of
      172 cats, two (1.2%) had definite dehiscence, and four (2.3%) had possible
      dehiscence. Low preoperative serum albumin was significantly associated with
      definite dehiscence in univariable analysis and with suspected dehiscence and
      death within 14 days in univariable analysis, but all odds ratios had wide 95%
      confidence intervals. A histopathological diagnosis of neoplasia was
      significantly associated with death within 14 days in univariable analysis. Of
      195 dogs, two (1.0%) had definite dehiscence, and three (1.5%) had possible
      dehiscence. In dogs, there was no association between any outcome measure and the
      putative risk factors. CLINICAL SIGNIFICANCE: Incidence of dehiscence following
      full-thickness gastrointestinal biopsy was low in this study. When determining
      the appropriateness of biopsy in individual cases, this information should be
      balanced against the potentially life-threatening consequences of dehiscence.

PMID- 28762503
TI  - Mechanomyography-Based Wearable Monitor of Quasi-Isometric Muscle Fatigue for
      Motor Neural Prostheses.
AB  - A motor neural prosthesis based on surface functional electrical stimulation
      (sFES) can restore functional movement (e.g., standing, walking) in patients with
      a spinal cord injury (SCI). sFES generates muscle contractions in antigravity
      muscles and allows balance-assisted standing. This induced standing has several
      benefits, such as improved cardiovascular function, decreased incidence of
      urinary infections, reduced joint contractures, and muscle atrophy. The duration
      of sFES assisted standing is limited due to the quick onset of muscle fatigue.
      Currently, there is no method available to reliably estimate real-time muscle
      fatigue during sFES. Simply monitoring the M-wave changes is not suitable due to
      the high signal disturbances that arise during multi-channel electrical
      stimulation. Mechanomyography (MMG) is immune to electrical stimulation artifacts
      and can be used to detect subtle vibrations on the surface of the skin related to
      activation of the underlying muscle's motor units (MU). The aim of this study was
      to develop a method for detecting muscle fatigue brought on by sFES. The method
      was tested in three different heads of the quadriceps muscle in SCI patients
      during electrically elicited quasi-isometric contraction. Six spinal cord-injured
      male volunteers, with no voluntary control of the quadriceps muscle participated
      in the study. Electrical bursts of voltage-controlled monophasic square pulses at
      frequencies of 1 kHz (50% duty cycle) at 50 Hz (15% duty cycle) were used to
      generate thigh muscle contractions that controlled the knee joint in the sagittal
      plane. The pulse amplitudes were set to position the knee joint at a 5 degrees 
      angle from the horizontal plane and when the knee angle dropped to 20 degrees 
      (e.g., the quadriceps were unable to hold the lower leg in the desired position),
      the test was terminated. Two data segments lasting 10 s each, at the beginning
      and end of each test, were analyzed. The muscle contraction was assessed by MMG
      sensors positioned on the rectus femoris, vastus lateralis, and vastus medialis
      muscles. Data segments were decomposed into 11 frequency bands using a Cauchy
      wavelet transform. In the initial time interval (non-fatigued muscle), the power
      peak was concentrated in the 11.31 Hz frequency band. In the final interval
      (muscle fatigued) this peak shifted to lower frequencies (2 and 6 Hz frequency
      bands). The decreased frequency was most prominent during the last 4 s of the
      recordings. It was shown that MMG could be used as a real-time indicator of
      muscle fatigue during FES-induced isometric contraction of quadriceps; hence, MMG
      could be used in closed-loop control as a fatigue detector. Subsequent studies
      for non-isometric contractions could possibly lead to prediction of muscle
      fatigue before contractile failure during functional use of the muscle.

PMID- 28762504
TI  - Computed tomographic findings in 12 cases of canine multi-centric lymphoma with
      splenic and hepatic involvement.
AB  - OBJECTIVES: To describe the CT findings in a population of dogs with multi
      centric lymphoma that involved the spleen and liver. MATERIALS AND METHODS:
      Clinical records between January 2008 and June 2015 were reviewed. Thoracic and
      abdominal CT examinations of patients diagnosed with multi-centric lymphoma were
      evaluated by a board-certified radiologist. A diagnosis of multi-centric lymphoma
      with splenic and hepatic involvement was based upon cytological identification
      and immunophenotyping of neoplastic lymphocytes in cellular samples harvested
      from a peripheral lymph node, the spleen and the liver. RESULTS: Twelve dogs were
      included in this study, of which 11 had B-cell lymphoma; immunophenotyping was
      inconclusive in one dog. The spleen appeared normal in seven dogs and nodules
      were identified in five dogs. Splenic nodules were hypoattenuating in four of
      five dogs and isoattenuating in one of five. After contrast administration, three
      of five appeared hypoattenuating and two of five isoattenuating. The liver
      appeared normal in 10 dogs and hepatic nodules were identified in two dogs. All
      hepatic nodules were isoattenuating before contrast and hypoattenuating following
      contrast administration. CLINICAL SIGNIFICANCE: The CT appearance of the spleen
      and liver was normal in the majority of dogs with multi-centric lymphoma. Fine
      needle aspiration of the spleen and liver is recommended when using CT to stage
      dogs with multi-centric lymphoma.

PMID- 28762505
TI  - Harnessing transcription for bioproduction in cyanobacteria.
AB  - Sustainable production of biofuels and other valuable compounds is one of our
      future challenges. One tempting possibility is to use photosynthetic
      cyanobacteria as production factories. Currently, tools for genetic engineering
      of cyanobacteria are not good enough to exploit the full potential of
      cyanobacteria. A wide variety of expression systems will be required to adjust
      both the expression of heterologous enzyme(s) and metabolic routes to the best
      possible balance, allowing the optimal production of a particular substance. In
      bacteria, transcription, especially the initiation of transcription, has a
      central role in adjusting gene expression and thus also metabolic fluxes of cells
      according to environmental cues. Here we summarize the recent progress in
      developing tools for efficient cyanofactories, focusing especially on
      transcriptional regulation.

PMID- 28762506
TI  - Towards CRISPR/Cas crops - bringing together genomics and genome editing.
AB  - Contents 682 I. 682 II. 683 III. 684 IV. 685 V. 685 VI. 688 VII. 690 VIII. 694
      694 References 694 SUMMARY: With the rapid increase in the global population and
      the impact of climate change on agriculture, there is a need for crops with
      higher yields and greater tolerance to abiotic stress. However, traditional crop
      improvement via genetic recombination or random mutagenesis is a laborious
      process and cannot keep pace with increasing crop demand. Genome editing
      technologies such as clustered regularly interspaced short palindromic repeat
      (CRISPR)/CRISPR-associated protein (CRISPR/Cas) allow targeted modification of
      almost any crop genome sequence to generate novel variation and accelerate
      breeding efforts. We expect a gradual shift in crop improvement away from
      traditional breeding towards cycles of targeted genome editing. Crop improvement
      using genome editing is not constrained by limited existing variation or the
      requirement to select alleles over multiple breeding generations. However,
      current applications of crop genome editing are limited by the lack of complete
      reference genomes, the sparse knowledge of potential modification targets, and
      the unclear legal status of edited crops. We argue that overcoming technical and
      social barriers to the application of genome editing will allow this technology
      to produce a new generation of high-yielding, climate ready crops.

PMID- 28762507
TI  - Increasing physical activity for veterans in the Mental Health Intensive Case
      Management Program: A community-based intervention.
AB  - AIMS AND OBJECTIVES: Individuals with severe mental illness (SMI), experience
      increased mortality-20 years greater disparity for men and 15 years greater
      disparity for women-compared to the general population (Thornicroft G. Physical
      health disparities and mental illness: The scandal of premature mortality. Br J
      Psychiatr. 2011;199:441-442). Numerous factors contribute to premature mortality
      in persons with SMI, including suicide and accidental death (Richardson RC,
      Faulkner G, McDevitt J, Skrinar GS, Hutchinson D, Piette JD. Integrating physical
      activity into mental health services for persons with serious mental illness.
      Psychiatr Serv. 2005;56(3):324-331; Thornicroft G. Physical health disparities
      and mental illness: The scandal of premature mortality. Br J Psychiatr.
      2011;199:441-442), but research has shown that adverse health behaviors-including
      smoking, low rate of physical activity, poor diet, and high alcohol consumption
      also significantly contribute to premature deaths (Jones J. Life expectancy in
      mental illness. Psychiatry Services. 2010. Retrieved from
      http://psychcentral.com/news/2010/07/13/life-expectancy-in-mental-illness). This
      quality improvement (QI) project sought to improve health and wellness for
      veterans in the Mental Health Intensive Case Management Program (MHICM), which is
      a community-based intensive program for veterans with SMI at risk for
      decompensation and frequent hospitalizations. At the time of this QI project, the
      program had 69 veterans who were assessed and treated weekly in their homes. The
      project introduced a pedometer steps intervention adapted from the VA MOVE!
      Program-a physical activity and weight management program-with the addition of
      personalized assistance from trained mental health professionals in the veteran's
      home environment. Because a large percentage of the veterans in the MHICM program
      had high blood pressure and increased weight, these outcomes were the focus of
      this project. Through mental health case management involvement and the comfort
      of their familiar living environment, veterans were assisted to meet their
      physical and mental health goals with a program that could easily be integrated
      into their daily lives. BACKGROUND: Healthy People 2020 developed goals to
      improve levels of physical activity and has ranked physical activity as a leading
      health indicator (US DHHS. Office of Disease Prevention and Health Promotion.
      Physical activity topic overview. In Healthy People 2020. 2016. Retrieved from
      https://www.healthypeople.gov/2020/topics-objectives/topic/physical-activity).
      Individuals with SMI are significantly less active than the general population
      (Shor and Shalev, 2014). It is sometimes difficult for the average individual to
      obtain the recommended 10,000 steps and even more difficult for those with SMI.
      Lifestyle modifications, in particular diet and exercise, are recommended for
      improvement of chronic disease outcomes (US Preventive Services Counseling Task
      Force, 2016). The health benefits of physical activity for people with SMI are
      mixed (Pearsall R, Smith D, Pelosi A, Geddes J. Exercise therapy in adults with
      serious mental illness: A systematic review and meta-analysis. BMC Psychiatr.
      2014;14:117). Some studies found significant physical health benefits, while
      others did not. However, according to a review by Soundy et al., physical
      exercise is shown to not only have physical benefits but also psychosocial
      benefits. One of the barriers that hinder participation in physical activities is
      accessibility (Shor and Shalev, 2014). Integrating a more personalized supported,
      and in-home pedometer program into mental healthcare should ensure better access
      to interventions that could possibly reverse the causes of premature death.
      METHODS: The program was offered to 69 veterans in the MHICM. Forty-nine agreed
      to start the program and 20 declined. Twenty-five clients actually started the
      program with 17 veterans completing it. Preimplementation data included
      collecting blood pressure and weight measures for all veterans in the MHICM
      program. Additionally, a focus group was held with case managers to obtain a
      group perspective on motivating veterans to participate in this program. Further,
      a teaching session was held to review pedometers use, the client video, the
      client booklet, methods for getting veterans started, and the progression of the
      walking intervention. The pedometer physical activity intervention continued for
      2 months. At the end of the 2 months, aggregate de-identified data on number of
      steps, blood pressure, and weight were collected. At the end of the program, the
      data were reviewed, synthesized, and analyzed, being careful to account for
      potentially intervening conditions and other chronic illnesses. RESULTS: The
      postimplementation data revealed that the mean weight decreased by 9 lbs. The
      percentage of controlled blood pressure increased from 60 to 84, while the
      percentage of uncontrolled blood pressure decreased from 40 to 16. CONCLUSION:
      Implementation of a multiple component personalized exercise intervention program
      for veterans with SMI contributed to reduction in weight and blood pressure.

PMID- 28762508
TI  - Mortality due to trauma in cats attending veterinary practices in central and
      south-east England.
AB  - OBJECTIVES: To identify important demographic and spatial factors associated with
      the risk of trauma and, more specifically, road traffic accident-related
      mortality, relative to other diagnoses in cats. METHODS: A sample of 2738 cats
      with mortality data derived from the VetCompass primary-care veterinary database
      was selected for detailed study. Generalised linear models investigated risk
      factors for mortality due to trauma and due to road traffic accidents versus
      other causes. RESULTS: A greater proportion of younger cats died through
      traumatic and road traffic accident-attributed causes relative to other causes of
      mortality. There was no apparent association of trauma- or road traffic accident
      related death with urban environments or areas where there is increased human
      population density. CLINICAL SIGNIFICANCE: These findings highlight that
      veterinary advice which aims to reduce the likelihood of death through trauma,
      and specifically road traffic accidents, should focus on demographic attributes
      including age. All geographical locations should be considered as of equal risk.

PMID- 28762509
TI  - Vertebral column regionalisation in Chinook salmon, Oncorhynchus tshawytscha.
AB  - Teleost vertebral centra are often similar in size and shape, but vertebral
      associated elements, i.e. neural arches, haemal arches and ribs, show regional
      differences. Here we examine how the presence, absence and specific anatomical
      and histological characters of vertebral centra-associated elements can be used
      to define vertebral column regions in juvenile Chinook salmon (Oncorhynchus
      tshawytscha). To investigate if the presence of regions within the vertebral
      column is independent of temperature, animals raised at 8 and 12  degrees C were
      studied at 1400 and 1530 degreedays, in the freshwater phase of the life cycle.
      Anatomy and composition of the skeletal tissues of the vertebral column were
      analysed using Alizarin red S whole-mount staining and histological sections. Six
      regions, termed I-VI, are recognised in the vertebral column of specimens of both
      temperature groups. Postcranial vertebrae (region I) carry neural arches and
      parapophyses but lack ribs. Abdominal vertebrae (region II) carry neural arches
      and ribs that articulate with parapophyses. Elastic- and fibrohyaline cartilage
      and Sharpey's fibres connect the bone of the parapophyses to the bone of the
      ribs. In the transitional region (III) vertebrae carry neural arches and
      parapophyses change stepwise into haemal arches. Ribs decrease in size, anterior
      to posterior. Vestigial ribs remain attached to the haemal arches with Sharpey's
      fibres. Caudal vertebrae (region IV) carry neural and haemal arches and spines.
      Basidorsals and basiventrals are small and surrounded by cancellous bone. Preural
      vertebrae (region V) carry neural and haemal arches with modified neural and
      haemal spines to support the caudal fin. Ural vertebrae (region VI) carry
      hypurals and epurals that represent modified haemal and neural arches and spines,
      respectively. The postcranial and transitional vertebrae and their respective
      characters are usually recognised, but should be considered as regions within the
      vertebral column of teleosts because of their distinctive morphological
      characters. While the number of vertebrae within each region can vary, each of
      the six regions is recognised in specimens of both temperature groups. This
      refined identification of regionalisation in the vertebral column of Chinook
      salmon can help to address evolutionary developmental and functional questions,
      and to support applied research into this farmed species.

PMID- 28762510
TI  - Chronic thoracoabdominal penetrating foreign body in a dog - a tranquiliser dart.

PMID- 28762512
TI  - Stress during pregnancy and its life-long consequences for the infant.

PMID- 28762511
TI  - Efficacy of Distal Perfusion Cannulae in Preventing Limb Ischemia During
      Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.
AB  - To date, no consensus exists regarding indication, technique, or efficacy of
      distal perfusion cannulae (DPC) in preventing limb ischemia among patients
      receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). We aim to
      examine the available literature and report association between DPC and risk of
      limb ischemia. PubMed/Medline, Scopus, Cochrane Central Register of Controlled
      Trials, Google Scholar, and bibliographies of included studies were searched from
      database inception until August 2016. Original studies describing the DPC
      placement technique and incidence of limb ischemia following DPC placement among
      VA-ECMO patients were included for systematic review. Studies with a comparison
      group of patients without DPC were included for meta-analysis. Two authors
      independently screened title/abstracts, reviewed full texts, and extracted data
      from the eligible studies. Meta-analysis was performed using the Mantel-Haenszel
      method under a random-effects model. Statistical heterogeneity was examined with
      the I2 statistic (RevMan Version 5.3). Of 542 title/abstracts screened, 62 full
      text articles were selected for review, yielding 22 retrospective observational
      studies, for a total of 779 patients with 132 limb ischemia events. There was
      significant variation in DPC indication, cannula type, and placement technique
      among the studies. Compared to no DPC, the presence of a DPC was associated with
      at least a 15.7% absolute reduction in the incidence of limb ischemia (9.74 vs.
      25.42%; risk ratio 0.41; 95% confidence interval 0.26-0.65, P < 0.01;
      heterogeneity statistic I2 = 28%). There was no statistically significant
      difference in mortality in the pooled dataset comparing DPC versus no DPC. In
      adults treated with VA-ECMO, DPC placement was associated with a lower incidence
      of limb ischemia. Currently no consensus guidelines exist regarding indication
      for DPC placement. Given the association described in this analysis, future
      prospective trials are warranted to establish a causal relationship and optimal
      technique for the use of DPC in patients treated with VA-ECMO.

PMID- 28762513
TI  - Differential expression of two genes Oct-4 and MUC5AC associates with poor
      outcome in patients with gastric cancer.
AB  - Gastric cancer (GC) is the most frequent leading cause of cancer-associated
      mortality worldwide that is linked to poor prognosis due to the lack of
      appropriate biomarkers. Our aim was to evaluate the MUC5AC and Oct-4 expression
      levels in GC and to assess their association with clinical factors.
      Immunohistochemical analysis (IHC) and qRT-PCR were performed in GC patients to
      examine the MUC5AC and Oct-4 expression levels. The mRNA level of MUC5AC was
      significantly decreased in tumour tissues compared with non-cancerous tissues
      (1.11 +/- 0.69 vs 3.7 +/- 0.71; P = .024). On the other hand, Oct-4 mRNA level
      was upregulated in tumour tissues as compared to normal tissues (2. 86 +/- 0.78
      vs 0.87 +/- 0.54; P = .0015). Decreased expression of MUC5AC was detected in 27
      patients (67.5%), while high to moderate expression levels were observed in 13
      cases (32.5%), but in normal tissues the expression levels of MUC5AC were
      increased (P = .001). The decreased expression of MUC5AC was associated with
      aggressive tumour characteristics, such as TNM stage (P = .023), histologic type
      (P = .012) and lymph node metastasis (P = .001). High expression of Oct-4 was
      detected in 24 tumour tissues (60%), while 16 cases (40%) showed low expression
      level. Increased Oct-4 expression was correlated with clinicopathological
      characteristics such TNM stage (P = .002), histologic type (P = .008) and lymph
      node metastasis (P = .001). Our results showed that high Oct-4 expression and the
      reduction of MUC5AC expression may be involved in the progression and an
      unfavorable prognosis of GC.

PMID- 28762514
TI  - Differential expression of microRNAs in luteinising hormone-treated mouse TM3
      Leydig cells.
AB  - Testosterone is primarily produced by Leydig cells of the mammalian male gonads.
      The cellular functions of Leydig cells are regulated by the hypothalamus
      pituitary-gonad axis, whereas the microRNA (miRNA) changes of LH-treated Leydig
      cells are unknown. Mouse TM3 Leydig cells were treated with LH, and deep
      sequencing showed that 29 miRNAs were significantly different between two groups
      (fold change of >1.5 or <0.5, p < .05), of which 27 were upregulated and two were
      downregulated. The differential expression of miR-29b-3p, miR-378b, miR-193b and
      miR-3695 was confirmed by quantitative real-time polymerase chain reaction.
      Bioinformatic analysis revealed that miRNAs regulated a large number of genes
      with different functions. Pathway analysis indicated that miRNAs were involved in
      the Wingless and INT-1, adenosine 5'-monophosphate-activated protein kinase, NF
      kappa B and Toll-like receptor signalling pathways. Results showed that miRNAs
      might be involved in the regulation of LH to Leydig cells.

PMID- 28762515
TI  - ELR+ chemokine-mediated neutrophil recruitment is involved in 2,4,6
      trinitrochlorobenzene-induced contact hypersensitivity.
AB  - Contact dermatitis is a form of delayed-type hypersensitivity characterized by
      localized thickening, papules, redness and vesicles of the skin. A model of
      contact dermatitis involving repeated challenge of a hapten is adapted to assess
      dermatitis as characterized by skin thickening. Recently, it was reported that
      neutrophils have crucial roles in contact hypersensitivity. We thus examined the
      involvement of CXC chemokines bearing the glutamic acid-leucine-arginine (ELR)
      motif ("ELR+ chemokines") and neutrophils in the ear swelling induced by 2,4,6
      trinitrochlorobenzene (TNCB) challenges in the present study. Mice were
      sensitized by application of TNCB on their abdominal skin. They were then
      challenged thrice with TNCB to the ear. The CXCR2 antagonist SB225002 (9 mg/kg,
      i.p.) was administered before each TNCB challenge. Gene expressions and protein
      levels of the ELR+ chemokines CXCL1, 2 and 5 was increased markedly in mouse ear
      after the final TNCB challenge. In addition, we indicated that gene expression of
      CXCL1 was enhanced in the epidermis and dermis upon TNCB challenge. Expression of
      the CXCL2 gene was enhanced in the epidermis, and that of the CXCL5 gene was
      enhanced in the dermis. The swelling induced by TNCB challenges was significantly
      attenuated by SB225002. Furthermore, the increases in myeloperoxidase activity,
      and expression of myeloperoxidase and neutrophil elastase induced by TNCB
      challenge in mouse ear were inhibited by SB225002. These data suggest that ear
      swelling resulting from TNCB challenges might be concerned by upregulated ELR+
      chemokine-induced neutrophil recruitment.

PMID- 28762516
TI  - Fluorescence in situ hybridisation sperm examination is significantly impaired in
      all categories of male infertility.
AB  - To study the outcome of FISH sperm examination in cases with sperm pathology and
      outline the potential correlation with certain chromosomal defects. A
      retrospective study of prospectively collected data was performed in IAKENTRO,
      Infertility Treatment Center. Rates of abnormal FISH semen examination were
      compared between male infertility patients and fertile controls. Detection of
      abnormal FISH semen examination as well as each chromosomal abnormality detected
      was correlated with each sperm deficiency (asthenozoospermia, oligozoospermia and
      teratozoospermia) in a univariate regression model. There were 72 male partners
      included, of which 52 male infertility patients and 20 controls. The rate of
      abnormal sperm FISH examination was significantly higher in patients' group
      (55.8% vs. 15.0% for controls, p = .002). Asthenozoospermia, oligozoospermia and
      teratozoospermia were significantly correlated with detection of abnormal FISH
      examination (p = .004, p = .01 and p < .001 respectively). Teratospermia was
      significantly correlated with increased aneuploidy rate for chromosome 17 (p =
      .005), chromosome X (p = .05) and Y (p = .03). FISH examination reveals pathology
      in a significant proportion of patients with sperm defects and should be
      recommended to achieve early detection of chromosomal defects that may postpone
      favourable reproductive outcome.

PMID- 28762517
TI  - Immunoaffinity based methods are superior to kits for purification of prostate
      derived extracellular vesicles from plasma samples.
AB  - BACKGROUND: The ability to isolate extracellular vesicles (EVs) such as exosomes
      or microparticles is an important method that is currently not standardized.
      While commercially available kits offer purification of EVs from biofluids, such
      purified EV samples will also contain non-EV entities such as soluble protein and
      nucleic acids that could confound subsequent experimentation. Ideally, only EVs
      would be isolated and no soluble protein would be present in the final EV
      preparation. METHODS: We compared commercially available EV isolation kits with
      immunoaffinity purification techniques and evaluated our final EV preparations
      using atomic force microscopy (AFM) and nanoscale flow cytometry (NFC). AFM is
      the only modality capable of detecting distinguishing soluble protein from EVs
      which is important for downstream proteomics approaches. NFC is the only
      technique capable of quantitating the proportion of target EVs to non-target EVs
      in the final EV preparation. RESULTS: To determine enrichment of prostate derived
      EVs relative to non-target MPs, anti-PSMA (Prostate Specific Membrane Antigen)
      antibodies were used in NFC. Antibody-based immunoaffinity purification generated
      the highest quality of prostate derived EV preparations due to the lack of
      protein and RNA present in the samples. All kits produced poor purity EV
      preparations that failed to deplete the sample of plasma protein. CONCLUSIONS:
      While attractive due to their ease of use, EV purification kits do not provide
      substantial improvements in isolation of EVs from biofluids such as plasma.
      Immunoaffinity approaches are more efficient and economical and will also
      eliminate a significant portion of plasma proteins which is necessary for
      downstream approaches.

PMID- 28762518
TI  - Preparation and characterization of a Cu (II)-IDA poly HEMA monolith syringe for
      proteomic applications.
AB  - Herein, we report the preparation of a metal-chelate immobilized hydrophilic poly
      hydroxyethylmethacrylate-based monolith of 100 MUL volume in a plastic syringe.
      The monolith is elastic in nature, contains well interconnected pores with a
      permeability (k) of 1.3 * 10-12  m2 . Immobilization of iminodiacetic acid (IDA)
      is performed via schiff base reaction. Adsortion of IgG on this copper-IDA
      monolith is of langmuir isotherm with a maximum adsorption capacity of ~25 mg IgG
      per g monolith. IgG adsorption capacity of this affinity monolith remained
      unaffected with increase of flow rate. This proposed metal-chelate monolith in
      syringe format has the potential for application in proteomics.

PMID- 28762519
TI  - Pathological changes in Sertoli cells and dysregulation of divalent metal
      transporter 1 with iron responsive element in the testes of idiopathic
      azoospermia patients.
AB  - Iron is essential for rapidly dividing spermatocytes during normal mammalian
      spermatogenesis. Decreased transferrin and transferrin receptor levels were
      observed in seminal plasma from idiopathic azoospermia (IA) patients, suggesting
      disturbed iron metabolism in IA testes. However, how Sertoli cells (SCs)
      contribute to the iron homoeostasis in IA is still unclear. In this study, we
      analysed 30 IA and 30 age-matched obstructive azoospermia (OA) patients
      undergoing testicular sperm aspiration (TESA). SCs hyperplasia was indicated by
      higher SC density and Ki-67 labelling index in the IA TESA specimens. The
      attenuated expression of superoxide dismutase (SOD) suggested an impaired
      antioxidative capacity in IA testes. We further detected increased levels of iron
      importer divalent metal transporter 1 with iron responsive element (DMT1 + IRE)
      in IA testes, whereas the increasing trend of iron exporter ferroportin 1 (FPN1)
      was not statistically significant. Next, we demonstrated that iron regulatory
      protein 1 (IRP1) and hypoxia-inducible factor-1alpha (HIF-1alpha), which can
      potentially bind to the IRE and hypoxia-responsive element in the DMT1 + IRE
      mRNA, were both up-regulated in IA testes. Unexpectedly, HIF-2alpha was down
      regulated in IA testes. These results indicate that there is a dysregulation of
      DMT1 + IRE in IA testes, which might due to the up-regulation of IRP1 and HIF
      1alpha.

PMID- 28762520
TI  - Nanomaterials as stationary phases and supports in liquid chromatography.
AB  - The development of various nanomaterials over the last few decades has led to
      many applications for these materials in liquid chromatography (LC). This review
      will look at the types of nanomaterials that have been incorporated into LC
      systems and the applications that have been explored for such systems. A number
      of carbon-based nanomaterials and inorganic nanomaterials have been considered
      for use in LC, ranging from carbon nanotubes, fullerenes and nanodiamonds to
      metal nanoparticles and nanostructures based on silica, alumina, zirconia and
      titanium dioxide. Many ways have been described for incorporating these
      nanomaterials into LC systems. These methods have included covalent
      immobilization, adsorption, entrapment, and the synthesis or direct development
      of nanomaterials as part of a chromatographic support. Nanomaterials have been
      used in many types of LC. These applications have included the reversed-phase,
      normal-phase, ion-exchange, and affinity modes of LC, as well as related methods
      such as chiral separations, ion-pair chromatography and hydrophilic interaction
      liquid chromatography. Both small and large analytes (e.g., dyes, drugs, amino
      acids, peptides and proteins) have been used to evaluate possible applications
      for these nanomaterial-based methods. The use of nanomaterials in columns,
      capillaries and planar chromatography has been considered as part of these
      efforts. Potential advantages of nanomaterials in these applications have
      included their good chemical and physical stabilities, the variety of
      interactions many nanomaterials can have with analytes, and their unique
      retention properties in some separation formats.

PMID- 28762521
TI  - Sperm cystic fibrosis transmembrane conductance regulator expression level is
      relevant to fecundity of healthy couples.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is relevant to sperm
      quality, sperm capacitation and male fertility. However, it is still unknown
      whether CFTR can be a potential parameter for fecundity prediction in healthy
      couples. In this study, 135 healthy couples were divided into groups according to
      their fertility. We demonstrated that the sperm CFTR expression level of healthy
      males who never impregnated their partners (49 cases, 38.68 +/- 2.71%) was
      significantly lower than that of fertile men (86 cases, 46.35 +/- 2.32%). Sperm
      CFTR expression level accurately corresponded with fertility through the logistic
      regression model. Receiver operating characteristic (ROC) curve analysis showed
      that the cut-off value of sperm CFTR expression level for fecundity prediction
      was 43.75%. Furthermore, cumulative pregnancy rates (CPRs) of CFTR > 43.75% group
      and CFTR <= 43.75% group during the follow-up periods were 80.6% and 49.3%
      respectively. Meanwhile, the mean time to pregnancy (TTP) of CFTR <= 43.75% group
      (26.79 +/- 2.35) was significantly longer than that of CFTR > 43.75% group (16.46
      +/- 2.42). Therefore, sperm CFTR expression level is relevant to fecundity of
      healthy couples and shows potential predictive capacity of fecundity.

PMID- 28762523
TI  - Prediction accuracy and variable selection for penalized cause-specific hazards
      models.
AB  - We consider modeling competing risks data in high dimensions using a penalized
      cause-specific hazards (CSHs) approach. CSHs have conceptual advantages that are
      useful for analyzing molecular data. First, working on hazards level can further
      understanding of the underlying biological mechanisms that drive transition
      hazards. Second, CSH models can be used to extend the multistate framework for
      high-dimensional data. The CSH approach is implemented by fitting separate
      proportional hazards models for each event type (iCS). In the high-dimensional
      setting, this might seem too complex and possibly prone to overfitting.
      Therefore, we consider an extension, namely "linking" the separate models by
      choosing penalty tuning parameters that in combination yield best prediction of
      the incidence of the event of interest (penCR). We investigate whether this
      extension is useful with respect to prediction accuracy and variable selection.
      The two approaches are compared to the subdistribution hazards (SDH) model, which
      is an established method that naturally achieves "linking" by working on
      incidence level, but loses interpretability of the covariate effects. Our
      simulation studies indicate that in many aspects, iCS is competitive to penCR and
      the SDH approach. There are some instances that speak in favor of linking the CSH
      models, for example, in the presence of opposing effects on the CSHs. We conclude
      that penalized CSH models are a viable solution for competing risks models in
      high dimensions. Linking the CSHs can be useful in some particular cases;
      however, simple models using separately penalized CSH are often justified.

PMID- 28762522
TI  - Hepatitis B cure: From discovery to regulatory approval.
AB  - The majority of persons currently treated for chronic hepatitis B require long
      term or lifelong therapy. New inhibitors of hepatitis B virus entry, replication,
      assembly, or secretion and immune modulatory therapies are in development. The
      introduction of these novel compounds for chronic hepatitis B necessitates a
      standardized appraisal of the efficacy and safety of these treatments and
      definitions of new or additional endpoints to inform clinical trials. To move the
      field forward and to expedite the pathway from discovery to regulatory approval,
      a workshop with key stakeholders was held in September 2016 to develop a
      consensus on treatment endpoints to guide the design of clinical trials aimed at
      hepatitis B cure. The consensus reached was that a complete sterilizing cure,
      i.e., viral eradication from the host, is unlikely to be feasible. Instead, a
      functional cure characterized by sustained loss of hepatitis B surface antigen
      with or without hepatitis B surface antibody seroconversion, which is associated
      with improved clinical outcomes, in a higher proportion of patients than is
      currently achieved with existing treatments is a feasible goal. Development of
      standardized assays for novel biomarkers toward better defining hepatitis B virus
      cure should occur in parallel with development of novel antiviral and immune
      modulatory therapies such that approval of new treatments can be linked to the
      approval of new diagnostic assays used to measure efficacy or to predict
      response. Combination of antiviral and immune modulatory therapies will likely be
      needed to achieve functional hepatitis B virus cure. Limited proof-of-concept
      monotherapy studies to evaluate safety and antiviral activity should be conducted
      prior to proceeding to combination therapies. The safety of any new curative
      therapies will be paramount given the excellent safety of currently approved
      nucleos(t)ide analogues. (Hepatology 2017).

PMID- 28762524
TI  - Resilience of experimentally seeded dietary traditions in wild vervets: Evidence
      from group fissions.
AB  - Controlled laboratory experiments have delivered extensive and compelling
      evidence for the diffusion and maintenance of socially learned behavior in
      primates and other animals. Such evidence is rarer in the wild, but we show that
      a behavior seeded in a majority of individuals within vervet monkey (Chlorocebus
      pygerythus) groups may be sustained across several years. Here, we report results
      of two natural fission events in such groups that offer novel evidence of the
      resilience of socially transmitted group norms of behavior. Before fission, high
      ranked females exhibited an almost exclusive adherence to a group preference
      among two food options, originally introduced through a distasteful additive in
      one option, but no longer present in repeated later tests. Because of rank
      dependent competition, low-ranked females ate more of the formerly distasteful
      food and so discovered it was now as palatable as the alternative. Despite this
      experience, low ranked females who formed the splinter groups then expressed a
      100% bias for the preferred option of their original parent group, revealing
      these preferences to be resilient. We interpret this effect as conformity to
      either the preferences of high rankers or of a majority in the parent group, or
      both. However, given fissioned individuals' familiarity with their habitat and
      experimental options, we question the adequacy of the informational function
      usually ascribed to conformity and discuss alternatives under a concept of
      "social conformity".

PMID- 28762525
TI  - Multiplicity considerations in subgroup analysis.
AB  - This paper deals with the general topic of subgroup analysis in late-stage
      clinical trials with emphasis on multiplicity considerations. The discussion
      begins with multiplicity issues arising in the context of exploratory subgroup
      analysis, including principled approaches to subgroup search that are applied as
      part of subgroup exploration exercises as well as in adaptive biomarker-driven
      designs. Key considerations in confirmatory subgroup analysis based on one or
      more pre-specified patient populations are reviewed, including a survey of
      multiplicity adjustment methods recommended in multi-population phase III
      clinical trials. Guidelines for interpretation of significant findings in several
      patient populations are introduced to facilitate the decision-making process and
      achieve consistent labeling across development programs. Copyright (c) 2017 John
      Wiley & Sons, Ltd.

PMID- 28762526
TI  - Thrombotic and hemorrhagic complications in idiopathic erythrocytosis.

PMID- 28762528
TI  - 19 F NMR isotropic chemical shift for efficient screening of fluorinated
      fragments which are racemates and/or display multiple conformers.
AB  - Fluorine ligand-based NMR spectroscopy is now an established method for
      performing binding screening against a macromolecular target. Typically, the
      transverse relaxation rate of the fluorine signals is monitored in the absence
      and presence of the target. However, useful structural information can sometimes
      be obtained from the analysis of the fluorine isotropic chemical shift. This is
      particularly relevant for molecules that are racemates and/or display multiple
      conformers. The large difference in fluorine isotropic chemical shift between
      free and bound state deriving mainly from the breaking and/or making of
      intramolecular and/or intermolecular hydrogen bonds allows the detection of very
      weak affinity ligands. According to our experimental results, racemates should
      always be included in the generation of the fluorinated fragment libraries. The
      selection or the availability of only one of the enantiomers for the fluorinated
      screening library could result in missing relevant chemical scaffold motifs.

PMID- 28762527
TI  - Outcomes after 18 months of eliglustat therapy in treatment-naive adults with
      Gaucher disease type 1: The phase 3 ENGAGE trial.
AB  - Eliglustat, an oral substrate reduction therapy, is a first-line treatment for
      adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive
      CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3
      ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in
      significant reductions in spleen and liver volumes and increases in hemoglobin
      concentration and platelet count compared with placebo. We report 18-month
      outcomes of patients who entered the trial extension period, in which all
      patients received eliglustat. Of 40 trial patients, 39 entered the extension
      period, and 38 completed 18 months. Absolute values and percent change over time
      were determined for spleen and liver volume, hemoglobin concentration, platelet
      count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers.
      For patients randomized to eliglustat in the double-blind period, continuing
      treatment with eliglustat for 9 more months resulted in incremental improvement
      of all disease parameters. For patients randomized to placebo in the double-blind
      period, eliglustat treatment during the 9-month, open-label period resulted in
      significant decrease of spleen and liver volumes and significant increase of
      hemoglobin and platelets, with a similar rate of change to patients who had
      received eliglustat in the double-blind period. Eliglustat treatment was also
      associated with improvement in bone marrow burden score, bone mineral density,
      and established biomarkers of Gaucher disease, including reduction of the
      bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of
      eliglustat in treatment-naive patients. Eliglustat was well-tolerated, and there
      were no new safety concerns with longer-term exposure.

PMID- 28762529
TI  - The impact of statin use on the efficacy of abiraterone acetate in patients with
      castration-resistant prostate cancer.
AB  - BACKGROUND: Statins compete with DHEAS for influx through the SLCO2B1
      transporter, which may prolong time to progression (TTP) on androgen deprivation
      therapy. Abiraterone acetate (AA) may also undergo SLCO-mediated transport. Based
      on preclinical findings showing antagonism, we hypothesized that statins may
      compete with AA for influx via SLCO2B1 and could negatively impact drug efficacy.
      METHODS: We queried two institutional clinical databases (Dana-Farber Cancer
      Institute [DFCI], Johns Hopkins University [JHU]) for CRPC patients treated with
      AA. Treatment duration was a surrogate for TTP. Associations between statin use
      and AA duration were estimated using the Kaplan-Meier method. Multivariable Cox
      regression modeling adjusted for known prognostic factors. RESULTS: Of the 224
      DFCI and 270 JHU patients included, the majority (96%) had metastatic disease.
      Nearly half (41% and 45%) were statin users. In the DFCI cohort, there was a
      trend toward longer AA duration in statin users: 14.2 versus 9.2 months (HR 0.79,
      95%CI: 0.57-1.09, P = 0.14). There was no association between statin use and AA
      duration in the JHU cohort: 8.3 versus 8.0 months (HR 0.89, 95%CI: 0.69-1.16, P =
      0.38) in the statin users versus non-users, except for a trend in patients that
      had not previously received docetaxel or enzalutamide (HR 0.79; 95%CI: 0.57
      1.10). CONCLUSIONS: Contrary to our initial hypothesis, there was a trend toward
      longer (rather than shorter) AA duration in statin users in the entire DFCI
      cohort and in the enzalutamide- and docetaxel-naive JHU patients. Together, these
      results do not support the hypothesis that statins interfere with AA efficacy.

PMID- 28762531
TI  - Purification and characterization of trypsin produced by gut bacteria from
      Anticarsia gemmatalis.
AB  - Purification of active trypsin in the digestive process of insects is essential
      for the development of potent protease inhibitors (PIs) as an emerging pest
      control technology and research into insect adaptations to dietary PIs. An
      important aspect is the presence of proteolytic microorganisms, which contribute
      to host nutrition. Here, we purified trypsins produced by bacteria Bacillus
      cereus, Enterococcus mundtii, Enterococcus gallinarum, and Staphylococcus xylosus
      isolated from the midgut of Anticarsia gemmatalis. The trypsins had a molecular
      mass of approximately 25 kDa. The enzymes showed increased activity at 40 degrees
      C, and they were active at pH values 7.5-10. Aprotinin, bis-benzamidine, and
      soybean Kunitz inhibitor (SKTI) significantly inhibited trypsin activity. The l-1
      tosyl-amido-2-phenylethylchloromethyl ketone (TPCK), pepstatin A, E-64,
      ethylenediamine tetraacetic acid, and calcium ions did not affect the enzyme
      activity at the concentrations tested. We infer the purified trypsins do not
      require calcium ions, by which they differ from the trypsins of other
      microorganisms and the soluble and insoluble trypsins characterized from A.
      gemmatalis. These data suggest the existence of different isoforms of trypsin in
      the velvetbean caterpillar midguts.

PMID- 28762530
TI  - High proportion of PD-1-expressing CD4+ T cells in adipose tissue constitutes an
      immunomodulatory microenvironment that may support HIV persistence.
AB  - We and others have demonstrated that adipose tissue is a reservoir for HIV.
      Evaluation of the mechanisms responsible for viral persistence may lead to ways
      of reducing these reservoirs. Here, we evaluated the immune characteristics of
      adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART)
      and in non-HIV-infected patients. We notably sought to determine whether adipose
      tissue's intrinsic properties and/or HIV induced alteration of the tissue
      environment may favour viral persistence. ART-controlled HIV infection was
      associated with a difference in the CD4/CD8 T-cell ratio and an elevated
      proportion of Treg cells in subcutaneous adipose tissue. No changes in Th1, Th2
      and Th17 cell proportions or activation markers expression on T cell (Ki-67, HLA
      DR) could be detected, and the percentage of CD69-expressing resident memory CD4+
      T cells was not affected. Overall, our results indicate that adipose-tissue
      resident CD4+ T cells are not extensively activated during HIV infection. PD-1
      was expressed by a high proportion of tissue-resident memory CD4+ T cells in both
      HIV-infected patients and non-HIV-infected patients. Our findings suggest that
      adipose tissue's intrinsic immunomodulatory properties may limit immune
      activation and thus may strongly contribute to viral persistence.

PMID- 28762532
TI  - Addressing small sample size bias in multiple-biomarker trials: Inclusion of
      biomarker-negative patients and Firth correction.
AB  - In recent years, numerous approaches for biomarker-based clinical trials have
      been developed. One of these developments are multiple-biomarker trials, which
      aim to investigate multiple biomarkers simultaneously in independent subtrials.
      For low-prevalence biomarkers, small sample sizes within the subtrials have to be
      expected, as well as many biomarker-negative patients at the screening stage. The
      small sample sizes may make it unfeasible to analyze the subtrials individually.
      This imposes the need to develop new approaches for the analysis of such trials.
      With an expected large group of biomarker-negative patients, it seems reasonable
      to explore options to benefit from including them in such trials. We consider
      advantages and disadvantages of the inclusion of biomarker-negative patients in a
      multiple-biomarker trial with a survival endpoint. We discuss design options that
      include biomarker-negative patients in the study and address the issue of small
      sample size bias in such trials. We carry out a simulation study for a design
      where biomarker-negative patients are kept in the study and are treated with
      standard of care. We compare three different analysis approaches based on the Cox
      model to examine if the inclusion of biomarker-negative patients can provide a
      benefit with respect to bias and variance of the treatment effect estimates. We
      apply the Firth correction to reduce the small sample size bias. The results of
      the simulation study suggest that for small sample situations, the Firth
      correction should be applied to adjust for the small sample size bias. Additional
      to the Firth penalty, the inclusion of biomarker-negative patients in the
      analysis can lead to further but small improvements in bias and standard
      deviation of the estimates.

PMID- 28762533
TI  - e-Health and new moms: Contextual factors associated with sources of health
      information.
AB  - OBJECTIVE: Guided by the Uses and Gratifications approach, to examine mothers'
      use and preference of e-Health media, and associated contextual factors. DESIGN
      AND SAMPLE: Cross-sectional survey of 165 mothers (White, African-American, and
      Hispanic) from a stratified random sample. MEASURES: Use of online media about
      mother-baby care; favorite websites about motherhood and best-liked features of
      Web sites; channel preferences (Web site, postal mail, text) for receiving three
      types of health information; and contextual factors, e.g., education. RESULTS:
      Media use ranged from 96% for health information searches about babies to 46% for
      YouTube viewing about mother-baby topics. Contextual factors, such as education,
      were associated with media use. Babycenter was the most frequently reported
      favorite Web site and rich, relevant information was the best-liked feature.
      Across three health topics (weight, stress/depression, parenting) mothers
      preferred receiving information by Web site, followed by postal mail and least by
      text messaging (chi2 statistics, p < .001). Stress and race/ethnicity were among
      factors associated with preferences. CONCLUSIONS: Mothers widely used e-Health
      related media, but use was associated with contextual factors. In public health
      efforts to reach new mothers, partnering with mother-favored Web sites, focusing
      on audience-relevant media, and adopting attributes of successful sites are
      recommended strategies.

PMID- 28762534
TI  - Perceptions of voluntary consent among jail diverted veterans with co-occurring
      disorders.
AB  - This study assessed perceptions of voluntary consent among 69 veterans who
      enrolled in a "jail diversion" program for co-occurring disorders. Perceptions
      were measured using modified items from the MacArthur Perceived Coercion and
      Negative Pressure Scales. A majority reported that they "chose to" (88.4%) or
      "felt free to" (85.5%) enroll. Most reported having "control over" (69.6%) and
      "more influence than anyone else" regarding (60.9%) their participation. About
      half reported that enrollment was "their idea" (49.3%). Fewer reported
      perceptions of negative pressure, including the feeling that someone "talked them
      into" enrolling (24.6%), "threatened them with the maximum criminal punishment"
      (13.0%), "offered or promised them something" (5.8%), or "forced" them to enroll
      (5.8%). Nobody felt "tricked, lied to, or fooled into" participating. Total
      negative pressure scores were higher in those with combat experience, U = 406.50,
      p = .016. Although potentially inappropriate pressures were reported, these data
      suggest that the majority perceived enrollment as voluntary.

PMID- 28762535
TI  - Anatomical complications of hysterectomy: A review.
AB  - Hysterectomy is the most commonly performed gynecological procedure in the United
      States with three possible surgical approaches; vaginal, abdominal and
      laparoscopic. As with any surgical procedure, various anatomical complications
      can arise. These include injuries to anatomical structures such as the urinary
      bladder, ureter, intestines, rectum, anus, and a multitude of nervous structures.
      Other complications include sexual dysfunction, vaginal cuff dehiscence, and
      urinary incontinence. Using standard search engines, the anatomical complications
      of hysterectomies are reviewed. In conclusion, surgeons who perform
      hysterectomies or are involved with postoperative hysterectomy patients should be
      familiar with the possible complications of this common procedure and the steps
      that can be taken to help reduce the risk of those complications. Clinicians
      should also inform their patients of the potential complications as they can
      affect lifestyle and comfort. Clin. Anat. 30:946-952, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28762536
TI  - A novel mr-based method for detection of cartilage delamination in
      femoroacetabular impingement patients.
AB  - In this study, quantitative magnetic resonance based measurements were used to
      evaluate T1rho and T2 mapping and heterogeneity in femoroacetabular impingement
      (FAI) patients with acetabular cartilage delamination and to determine the
      ability of these quantitative MR-based measurements in detecting delamination.
      Unilateral hip joint MR-scans of 36 FAI patients with arthroscopically-confirmed
      acetabular cartilage delamination and 36 age, gender, and BMI matched controls
      were obtained. T1rho and T2 mapping and heterogeneity of the hip joint articular
      cartilage were assessed in both groups using voxel-based relaxometry (VBR).
      Quantitative MR-based measurements were compared using statistical parametric
      mapping (SPM). Receiver operating characteristic (ROC) analysis was used to
      assess the ability of these quantitative measurements in detecting delamination
      by calculating the area under the curve (AUC). Pearson partial correlations (r)
      were used to assess for associations between T1rho and T2 radial heterogeneity
      with the alpha angle in FAI patients. T1rho and T2 global acetabular values were
      significantly higher in FAI patients with a focal increase within the posterior
      acetabular cartilage. FAI patients exhibited increased anterior superior
      acetabular T1rho and T2 heterogeneity and both of these measures demonstrated a
      strong ability to detect acetabular cartilage delamination (T1rho AUC: 0.96, p <
      0.001; T2 AUC: 0.93, p < 0.001). FAI patients with a larger alpha angle exhibited
      increased anterior superior acetabular T1rho (r = 0.48, p = 0.02) and T2 (r =
      0.42, p = 0.03) heterogeneity. T1rho and T2 heterogeneity within the anterior
      superior acetabular cartilage was shown to be a sensitive measure in detecting
      delamination and may prove beneficial to clinicians in determining optimal
      interventions for FAI patients. (c) 2017 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res 36:971-978, 2018.

PMID- 28762537
TI  - Affordability of Fertility Treatments and Multiple Births in the United States.
AB  - BACKGROUND: Affordability plays an important role in the utilisation of in vitro
      fertilisation (IVF) and non-IVF fertility treatments. Fertility treatments are
      associated with increased risk of multiple births. The objective of this study
      was to investigate the association between the affordability of fertility
      treatments across US states and the percentage of multiple births due to natural
      conception, non-IVF treatments, and IVF, and the association between these
      percentages and state-specific multiple birth rates. METHODS: State-specific per
      capita disposable personal income and state-specific infertility insurance
      mandates were used as measures of affordability. Maternal age-adjusted
      percentages of multiple births due to natural conception, non-IVF treatments, and
      IVF were estimated for each state using birth certificate and IVF data. Scatter
      plots and regression analysis were used to explore associations between state
      level measures of affordability, the percentage of multiple births due to natural
      conception and fertility treatments, and state-specific multiple birth rates.
      RESULTS: In 2013, age-adjusted contributions of natural conception, non-IVF
      fertility treatments, and IVF to multiple births in US were 58.2, 22.8, and 19.0%
      respectively. States with greater affordability of fertility treatments had
      higher percentages of multiples due to IVF and lower percentages due to natural
      conception. Higher percentages of multiples due to IVF and lower percentages due
      to natural conception were associated with higher state-specific multiple birth
      rates. CONCLUSION: Increasing affordability of fertility treatments may increase
      state-specific multiple birth rates. Policies and treatment practices encouraging
      single-gestation pregnancies may help reduce multiple births resulting from these
      treatments.

PMID- 28762538
TI  - Assessing patient-centred communication in teaching: a systematic review of
      instruments.
AB  - CONTEXT: Patient-centred communication is a key component of patient centredness
      in medical care. Therefore, adequate education in and assessment of patient
      centred communication skills are necessary. In general, feedback on communication
      skills is most effective when it is provided directly and is systematic. This
      calls for adequate measurement instruments. OBJECTIVES: The aim of this study was
      to provide a systematic review of existing instruments that measure patient
      centredness in doctor-patient communication and can be used to provide direct
      feedback. METHODS: A systematic review was conducted using an extensive validated
      search strategy for measurement instruments in PubMed, EMBASE, PsycINFO and
      CINAHL. The databases were searched from their inception to 1 July 2016. Articles
      describing the development or evaluation of the measurement properties of
      instruments that measure patient centredness (by applying three or more of the
      six dimensions of a published definition of patient centredness) in doctor
      patient communication and that can be used for the provision of direct feedback
      were included. The methodological quality of measurement properties was evaluated
      using the COSMIN checklist. RESULTS: Thirteen articles describing 14 instruments
      measuring patient centredness in doctor-patient communication were identified.
      These studies cover a wide range of settings and patient populations, and vary in
      the dimensions of patient centredness applied and in methodological quality on
      aspects of reliability and validity. CONCLUSIONS: This review gives a
      comprehensive overview of all instruments available for the measurement of
      patient centredness in doctor-patient communication that can be used for the
      provision of direct feedback and are described in the literature. Despite the
      widely felt need for valid and reliable instruments for the measurement of
      patient-centred communication, most of the instruments currently available have
      not been thoroughly investigated. Therefore, we recommend further research into
      and enhancement of existing instruments in terms of validity and reliability,
      along with enhancement of their generalisability, responsiveness and aspects of
      interpretability in different contexts (real patients, simulated patients,
      doctors in different specialties, etc.). Comprehensibility and feasibility should
      also be taken into account.

PMID- 28762539
TI  - The impact of antibody profile in thrombosis associated with primary
      antiphospholipid syndrome.
AB  - Triple positivity (TP) for antiphospholipid antibodies(aPL) may identify aPL
      carriers with poorer prognosis. The clinical impact of TP in primary
      antiphospholipid syndrome(PAPS) remains unclear and further clinical evidences
      are needed to validate TP as a marker of severity. The aim of this study was to
      evaluate the impact of TP on the clinical course of PAPS with thrombosis(t-PAPS).
      We performed a retrospective analysis of a cohort of t-PAPS patients, comparing
      groups of patients with TP and non-TP profiles according to their demographic,
      clinical and laboratory features. We included 105 patients with t-PAPS, the
      median follow-up time of 3.7 years. Twenty-two patients(21%) had TP; the
      demographic distribution, the presence of cardiovascular risk factors and the
      site of thrombosis were similar between TP and non-TP patients. The frequency of
      thrombotic events did not differ between TP and non-TP patients during the study
      period. Pregnancy morbidities were more frequent in women with t-PAPS and TP than
      in those with non-TP profile (80% vs. 52.8%, P = 0.05). Patients with t-PAPS and
      TP presented, at diagnosis, higher dRVVT ratio (median R = 2.44 vs. 1.57, P <
      0.0001), higher aCL titer (median = 50UI vs. 35 UI, P < 0.0001), lower C3 levels
      (median = 1.08 vs. 1.30 mg dL-1 , P = 0.001), lower C4 levels (median = 0.22 vs.
      0.25 mg dL-1 , P = 0.05) and higher frequency of positive ANA test (50% vs. 20%,
      P = 0.008) than patients with t-PAPS and non-TP. Lower-than-normal levels of C3
      was independently associated with TP (OR = 5.1, P = 0.02). The presence of TP in
      patients with t-PAPS was associated with immune derangement, with no effect on
      the clinical course of the disease.

PMID- 28762540
TI  - Three dimensional ultrasound and hdlive technology as possible tools in teaching
      embryology.
AB  - Embryology is an important subject in order to gain an understanding of medicine
      and surgery; however, sometimes students find the subject difficult to grasp and
      apply to clinical practice. Modern imaging techniques can be useful aids in
      teaching and understanding embryology. Imaging techniques have very rapidly
      evolved over the last few years, advancing from two- to three-dimensional (3D)
      ultrasound. HDlive is an innovative ultrasound technique that generates near
      realistic images of the human fetus. In order to evince the capabilities of 3D
      ultrasound and HDlive technology in teaching embryology, we evaluated using this
      technique the normal evolution of the embryo and fetus from the fifth to eleventh
      week of amenorrhea. Our conclusion is that by yielding clear and impressive
      images, 3D ultrasound and HDlive could be useful tools in teaching embryology to
      medical students. Clin. Anat. 30:953-957, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28762541
TI  - Real-world effectiveness and safety of paritaprevir/ritonavir, ombitasvir, and
      dasabuvir with or without ribavirin for patients with chronic hepatitis C virus
      genotype 1b infection in Taiwan.
AB  - BACKGROUND AND AIM: The real-world effectiveness and safety of
      paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) remain limited for East
      Asian hepatitis C virus genotype 1b (HCV-1b) patients. The study aimed to
      evaluate the antiviral responses of PrOD-based regimens for HCV-1b patients in
      Taiwan. METHODS: The study performed a retrospective analysis of 103 HCV-1b
      patients receiving PrOD with or without ribavirin (RBV) for 12 weeks. Data were
      analyzed to assess the on-treatment and off-therapy HCV viral load and on
      treatment adverse events. The pre-specified characteristics related to sustained
      virologic response 12 weeks off therapy (SVR12 ) were compared. RESULTS: At
      treatment week 4, 100 of 102 patients (98.0%) had serum HCV RNA level < 25 IU/mL.
      The SVR12 was achieved in 101 of 103 patients (98.1%, [95% confidence interval:
      93.2-99.5%]). All except one (99.0%) patients tolerated treatment well without
      treatment interruption. One cirrhotic patient discontinued treatment at week 1
      due to hepatic decompensation. Twenty-four patients (23.3%) had >= grade 2
      elevation in total bilirubin levels, and 21 of them (87.5%) had indirect type
      hyperbilirubinemia. The stratified SVR12 rates were comparable in terms of sex,
      age, body mass index, prior treatment experience, hepatitis B virus surface
      antigen status, RBV usage, baseline and week 2 viral load, renal function, and
      hepatic fibrosis stage. CONCLUSIONS: Paritaprevir/ritonavir, ombitasvir, and
      dasabuvir with or without RBV are efficacious and generally well tolerated for
      treatment of HCV-1b patients in Taiwan.

PMID- 28762543
TI  - Engineered red blood cells as therapeutic agents.

PMID- 28762542
TI  - Response to comment on the IUGA/ICS joint report on the terminology for the
      conservative and nonpharmacological management of female pelvic floor
      dysfunction.

PMID- 28762544
TI  - Coexisting depressive symptoms do not limit the benefits of chronic
      neuromodulation: A study of over 200 patients.
AB  - AIMS: To examine the relationship between coexisting depressive symptoms and
      outcomes after staged neuromodulation procedures for refractory urological
      symptoms. METHODS: Adults who enrolled in a prospective database and completed a
      Personal Health Questionnaire Depression Scale (PHQ-8) at baseline were reviewed.
      The PHQ-8 and Generalized Anxiety Disorder (GAD-7) assessed depressive/anxiety
      symptoms pre and 6 months post device implant. Urological symptoms were assessed
      with The Interstitial Cystitis Symptom Index/Problem Index (ICSI-PI) and
      Overactive Bladder Questionnaire (OAB-q) at baseline, 3 and 6 months, and Global
      Response Assessments (GRA) post implant. Subjects, grouped by PHQ <10 and PHQ
      >=10, were compared with Pearson's Chi-square, Fisher's Exact or Wilcoxon rank
      test, and Spearman's correlations. RESULTS: In 117 PHQ <10 and 84 PHQ >=10
      patients, age differed (mean 59 vs 52 years; P = 0.001), and PHQ <10 had lower
      GAD-7, ICSI-PI, and OAB-q scores at baseline (P < 0.0001, P = 0.0003, and P <
      0.0008, respectively). Implantation rates were similar between groups.
      Reoperation and complication rates within the first 6 months did not differ,
      similar proportions (majority) were improved on the GRA at each time point, and
      ICSI-PI and OAB-q scores improved significantly. PHQ scores only improved
      significantly for those with baseline PHQ >=10. Baseline PHQ strongly correlated
      with GAD-7 at baseline and 6 months, and baseline ICSI-PI. Change in PHQ
      positively correlated with the change in GAD-7, 6 month ICSI-PI, and change in
      ICSI-PI from baseline to 6 months. CONCLUSIONS: Coexisting depressive symptoms do
      not limit the efficacy of neuromodulation and PHQ improvements correlate with
      improved anxiety and bladder symptoms.

PMID- 28762545
TI  - Epigenetic risk score improves prostate cancer risk assessment.
AB  - BACKGROUND: Early detection of aggressive prostate cancer (PCa) remains crucial
      for effective treatment of patients. However, PCa screening remains controversial
      due to a high rate of overdiagnosis and overtreatment. To better reconcile both
      objectives, more effective methods for assessing disease severity at the time of
      diagnosis are needed. METHODS: The relationship between DNA-methylation and high
      grade PCa was examined in a cohort of 102 prospectively enrolled men who received
      standard 12-core prostate biopsies. EpiScore, an algorithm that quantifies the
      relative DNA methylation intensities of GSTP1, RASSF1, and APC in prostate biopsy
      tissue, was evaluated as a method to compensate for biopsy under-sampling and
      improve risk stratification at the time of diagnosis. RESULTS: DNA-methylation
      intensities of GSTP1, RASSF1, and APC were higher in biopsy cores from men
      diagnosed with GS >= 7 cancer compared to men with diagnosed GS 6 disease. This
      was confirmed by EpiScore, which was significantly higher for subjects with high
      grade biopsies and higher NCCN risk categories (both P < 0.001). In patients
      diagnosed with GS >= 7, increased levels of DNA-methylation were present, not
      only in the high-grade biopsy cores, but also in other cores with no or low-grade
      disease (P < 0.001). By combining EpiScore with traditional clinical risk factors
      into a logistic regression model, the prediction of high GS reached an AUC of
      0.82 (95%CI: 0.73-0.91) with EpiScore, DRE, and atypical histological findings as
      most important contributors. CONCLUSIONS: In men diagnosed with PCa, DNA
      methylation profiling can detect under-sampled high-risk PCa in prostate biopsy
      specimens through a field effect. Predictive accuracy increased when EpiScore was
      combined with other clinical risk factors. These results suggest that EpiScore
      could aid in the detection of occult high-grade disease at the time of diagnosis,
      thereby improving the selection of candidates for Active Surveillance.

PMID- 28762546
TI  - Dynamic classification using credible intervals in longitudinal discriminant
      analysis.
AB  - Recently developed methods of longitudinal discriminant analysis allow for
      classification of subjects into prespecified prognostic groups using longitudinal
      history of both continuous and discrete biomarkers. The classification uses
      Bayesian estimates of the group membership probabilities for each prognostic
      group. These estimates are derived from a multivariate generalised linear mixed
      model of the biomarker's longitudinal evolution in each of the groups and can be
      updated each time new data is available for a patient, providing a dynamic (over
      time) allocation scheme. However, the precision of the estimated group
      probabilities differs for each patient and also over time. This precision can be
      assessed by looking at credible intervals for the group membership probabilities.
      In this paper, we propose a new allocation rule that incorporates credible
      intervals for use in context of a dynamic longitudinal discriminant analysis and
      show that this can decrease the number of false positives in a prognostic test,
      improving the positive predictive value. We also establish that by leaving some
      patients unclassified for a certain period, the classification accuracy of those
      patients who are classified can be improved, giving increased confidence to
      clinicians in their decision making. Finally, we show that determining a stopping
      rule dynamically can be more accurate than specifying a set time point at which
      to decide on a patient's status. We illustrate our methodology using data from
      patients with epilepsy and show how patients who fail to achieve adequate seizure
      control are more accurately identified using credible intervals compared to
      existing methods.

PMID- 28762547
TI  - Correlation of inflammatory mediators in prostatic secretion with chronic
      prostatitis and chronic pelvic pain syndrome.
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common clinical
      syndrome, and the mechanisms underlying the relationship between CP/CPPS and ED
      are still unclear. This study aimed to investigate the differential expression of
      40 inflammatory mediators in patients with CP/CPPS and to demonstrate whether
      these mediators related to the severity of erectile function. Eighty cases of
      patients with CP/CPPS were selected, including 40 cases of IIIA and 40 cases of
      IIIB, with 20 cases of healthy men as controls. After collecting their expressed
      prostatic secretion, cytokines levels in EPS were determined by ELISA using ELISA
      kits. The IIEF-5 questionnaire was used to evaluate erectile function. IIEF-5
      scores were significantly lower in the IIIA and IIIB groups than those in the
      control group. The expression of IL-8, IL-1beta and ICAM-1 was markedly higher in
      the IIIA and IIIB groups than in the control group. The expression of IL-8, IL
      1beta and ICAM-1 in the IIIA group was higher than that in the IIIB group. The
      expression of IL-8, IL-1beta and ICAM-1 was negatively correlated with IIEF-5
      scores in both IIIA and IIIB patients. In conclusion, IL-8, IL-1beta and ICAM-1
      are possible indicators for the clinical diagnosis of CP/CPPS and evaluation of
      erectile function on patients with CP/CPPS.

PMID- 28762549
TI  - Patient-targeted websites on overactive bladder: What are our patients reading?
AB  - AIMS: Patients often turn to the Internet for information on medical conditions.
      We sought to evaluate the quality and readability of highly visible websites on
      overactive bladder (OAB). METHODS: A survey of 42 consecutive patients attending
      outpatient urogynecology clinics was performed to identify the most commonly used
      Internet search engines and search terms for information on OAB. The three most
      commonly used search engines (Google, Bing, and Yahoo!) were then queried using
      the three most commonly used search terms. The first 20 relevant websites from
      each search were reviewed. After excluding duplicates, 35 websites were analyzed.
      Website quality of information on OAB was evaluated using the DISCERN score, JAMA
      benchmark criteria, and Health on the Net code (HONcode) accreditation status.
      Readability was assessed using the Simplified Measure of Gobbledygook (SMOG) and
      Dale-Chall indices. RESULTS: Websites were classified as advertisement/commercial
      (31%), health portal (29%), professional (26%), patient group (6%), and other
      (9%). The overall mean DISCERN score was 44 +/- 18 (maximum possible score of
      80). Three websites (9%) met all four JAMA benchmark criteria. Seventeen percent
      of websites provided adequate information on content authorship and
      contributions. Median SMOG and Dale-Chall indices were 9.9 (IQR 9.3-11.2) and 9.0
      (IQR 8.1-9.4), respectively. Nine websites (26%) were HONcode certified.
      CONCLUSIONS: Popular websites on OAB are of low quality, written for a high
      school to college-level readership, and often lack adequate information to assess
      the potential for commercial bias. Patients should be cautioned that incomplete
      and potentially biased information on OAB is prevalent online.

PMID- 28762548
TI  - Health literacy, cognition, and urinary incontinence among geriatric inpatients
      discharged to skilled nursing facilities.
AB  - AIMS: To investigate the association between health literacy and cognition and
      nursing and patient-reported incontinence in a geriatric inpatient population
      transitioning to skilled nursing facilities (SNF). METHODS: Health literacy,
      depression, and cognition were assessed via the Brief Health Literacy Screen
      (BHLS), Geriatric Depression Scale 5-item (GDS) and Brief Interview for Mental
      Status (BIMS), respectively. Multivariable logistic regression assessed the
      association between BHLS score and incontinence by: (1) nursing-reported urinary
      incontinence during hospitalization; and (2) patient self-reported "bladder
      accidents" in the post-enrollment study interview. RESULTS: A total of 1556
      hospitalized patients aged 65 and older met inclusion criteria, of whom 922
      (59.3%) were women and 1480 had available BHLS scores. A total of 464 (29.8%) and
      515 (33.1%) patients had nursing-reported and self-reported urinary incontinence,
      respectively. Nursing-reported incontinence was significantly associated with
      lower BHLS (ie, poorer health literacy) (aOR 0.93, 95%CI 0.89-0.99) and BIMS (ie,
      poorer cognition) (aOR 0.90, 95%CI 0.83-0.97) scores and need for assistance with
      toileting (aOR 7.08, 95%CI 2.16-23.21). Patient-reported incontinence was
      significantly associated with female sex (aOR 1.62, 95%CI 1.19-2.21), increased
      GDS score (ie, greater likelihood of depression) (aOR 1.22, 95%CI 1.10-1.36) and
      need for assistance with toileting (aOR 2.46, 95%CI 1.26-4.79). CONCLUSIONS:
      Poorer health literacy and cognition are independently associated with an
      increased likelihood of nursing-reported urinary incontinence among geriatric
      inpatients transitioning to SNF. Practitioners should consider assessment of
      health literacy and cognition in frail patients at risk for urinary incontinence
      and that patient and nursing assessment may be required to capture the diagnosis.

PMID- 28762550
TI  - Exploring collaboration in a community-academic partnership.
AB  - OBJECTIVE: Community-academic relationships characterized by collaboration can
      contribute to the preparation of public health nursing students, sustainability
      of partnerships over time, and innovative solutions to pressing health problems.
      The purpose of this study was to describe and understand relationship
      characteristics in a community-academic partnership over time and how the
      relationship could be improved. DESIGN AND SAMPLE: A descriptive case study was
      conducted. Study participants included partnership staff, organizational leaders,
      community residents, and student nurses involved in the partnership between 2011
      and 2015. MEASURES: Methods included focus groups, documents, interviews, and
      surveys. RESULTS: Four main themes emerged and include analysis findings that
      capture the relationship characteristics between partners and how the
      relationship could be improved: Time, Communication, Goals, and Sharing.
      CONCLUSIONS: Findings on how to improve relationship characteristics offer clear
      suggestions for academic and community partners on ways to move toward
      collaborative partnerships that can address health inequities and develop a
      competent and advanced public health nursing workforce in the 21st century.

PMID- 28762551
TI  - Monocarboxylate transporter 1 is a key player in glioma-endothelial cell
      crosstalk.
AB  - Glioblastoma (GBM) is one of the most glycolytic and angiogenic human tumors,
      characteristics that contribute to the poor prognosis associated with this type
      of tumor. A lactate shuttle has been described between tumor cells and
      endothelial cells (ECs), with the monocarboxylate transporters (MCTs) acting as
      important players in this tumor-EC communication. In this study, we aimed to
      understand how the tumor microenvironment modulates EC metabolism, and to
      characterize the role of MCTs in the glioma-brain EC crosstalk. Exposure of human
      brain microvascular ECs (HBMEC) to GBM cell-conditioned media increased the
      expression of MCT1, which corresponded to activation of oxidative metabolism and
      an increase in angiogenic capacity, as determined by increased proliferation,
      migration, and vessel assembly. Lactate depletion from the microenvironment or
      inhibition of lactate uptake in HBMEC induced an increase in lactate production
      and a decrease in proliferation, migration, and vessel assembly. Moreover,
      addition of lactate to HBMEC media promoted activation of AKT and AMPK pathways
      and increased expression in NFkappaB, HIF-1alpha, and the lactate receptor GPR81.
      Here, we demonstrate a role for MCT1 as a mediator of lactate signaling between
      glioma cells and brain ECs. Our results suggest that MCT1 can mediate EC
      metabolic reprograming, proliferation, and vessel sprouting in response to tumor
      signaling. Thus, targeting MCT1 in both tumor cells and brain EC may be a
      promising therapeutic strategy for the treatment of GBM.

PMID- 28762552
TI  - Application of Computer-Aided Diagnosis on Breast Ultrasonography: Evaluation of
      Diagnostic Performances and Agreement of Radiologists According to Different
      Levels of Experience.
AB  - OBJECTIVES: To investigate the feasibility of a computer-aided diagnosis (CAD)
      system (S-Detect; Samsung Medison, Co, Ltd, Seoul, Korea) for breast
      ultrasonography (US), according to radiologists with various degrees of
      experience in breast imaging. METHODS: From December 2015 to March 2016, 119
      breast masses in 116 women were included. Ultrasonographic images of the breast
      masses were retrospectively reviewed and analyzed by 2 radiologists specializing
      in breast imaging (7 and 1 years of experience, respectively) and S-Detect,
      according to the individual ultrasonographic descriptors from the fifth edition
      of the American College of Radiology Breast Imaging Reporting and Data System and
      final assessment categories. Diagnostic performance and the interobserver
      agreement among the radiologists and S-Detect was calculated and compared.
      RESULTS: Among the 119 breast masses, 54 (45.4%) were malignant, and 65 (54.6%)
      were benign. Compared to the radiologists, S-Detect had higher specificity (90.8%
      compared to 49.2% and 55.4%) and positive predictive value (PPV; 86.7% compared
      to 60.7% and 63.8%) (all P < .001). Both radiologists had significantly improved
      specificity, PPV, and accuracy when using S-Detect compared to US alone (all P <
      .001). The area under the receiving operating characteristic curves of the both
      radiologists did not show a significant improvement when applying S-Detect
      compared to US alone (all P > .05). Moderate agreement was seen in final
      assessments made by each radiologist and S-Detect (kappa = 0.40 and 0.45,
      respectively). CONCLUSIONS: S-Detect is a clinically feasible diagnostic tool
      that can be used to improve the specificity, PPV, and accuracy of breast US, with
      a moderate degree of agreement in final assessments, regardless of the experience
      of the radiologist.

PMID- 28762553
TI  - Evaluation of pelvic floor muscle strength and its correlation with sexual
      function in primigravid and non-pregnant women: A cross-sectional study.
AB  - AIMS: We aimed to compare pelvic floor muscle (PFM) strength and sexual function
      in primigravid and non-pregnant women and compare PFM strength between those who
      exhibited and did not exhibit sexual dysfunction. METHODS: A cross-sectional
      observational study was conducted. The sample consisted of 154 women, including
      76 primigravid and 78 non-pregnant women. The inclusion criteria were as follows:
      non-pregnant nulliparous women or primigravid women who were pregnant with a
      single foetus at least 14 weeks of gestational age and reported having sexual
      intercourse at least once during the last 4 weeks. The exclusion criteria were as
      follows: inability to contract the PFMs and prior urogynaecologic surgery. PFM
      strength was assessed via vaginal palpation (using the Modified Oxford Scale) and
      vaginal squeeze pressure (using the PeritronTM manometer). Sexual function was
      assessedusing the Female Sexual Function Index (FSFI) questionnaire. Sexual
      dysfunction was identified based on low FSFI scores.The data were analyzed using
      the Mann-Whiney and Spearman correlation tests. RESULTS: To discussion,
      primigravid women had lower FSFI scores and lower PFM strength than non-pregnant
      women. Women with sexual dysfunction had lower PFM strength than women without
      sexual dysfunction, as indicated by vaginal palpation (scores of 2 out of 5 and 4
      out of 5, respectively; P < 0.001) and vaginal squeeze pressure (17.5 and 36.8 cm
      H2 O, P < 0.001, respectively)regardless of whether they were non-pregnant
      nulliparous women and primigravid. CONCLUSIONS: Primigravid women exhibited worse
      sexual function and lower PFM strength than non-pregnant women. Women who had
      higher FSFI scores demonstrated greater PFM strength.

PMID- 28762554
TI  - Meaning and death-thought accessibility.
AB  - Meaning is a central feature in human life, but death can disrupt a sense of
      meaning. Two experiments tested the hypothesis that meaning in life and meaning
      in death are distinct types of meaning when mortality is salient and
      differentially affect death-thought accessibility (DTA). In Experiment 1,
      imagining a specific scenario in which meaning is preserved beyond death reduced
      DTA relative to a standard mortality salience prime; moreover, these effects were
      not due to changes in self-esteem. In Experiment 2, imagining a meaningful life
      when mortality is salient elicited greater DTA, whereas imagining meaning in
      death elicited less DTA. Imbuing death with meaning attenuates DTA, whereas
      meaning in life increases DTA.

PMID- 28762555
TI  - Elucidation of the Conformation of Polyglycine Organo-Polyoxotungstates: Evidence
      for Zipper Folding.
AB  - The conformation of a family of alpha1 and alpha2 polyglycine-containing organo
      polyoxometalates was determined through a mixed experimental/molecular dynamics
      approach. The flexible peptide arm folds around the metal oxide surface in a
      rigid arrangement in low to average polarity solvents. The topology of the hybrid
      is the main factor that determines which oxos from the metal-oxide surface accept
      a H-bond from the closest amino acid. The rest of the peptide follows in a zipper
      mechanism that establishes a H-bond network that locks the system. The covalent
      constraint leads to a new type of H-bond where two consecutive amino acids clamp
      down terminal oxo ligands.

PMID- 28762557
TI  - Insights from Cowichan: A Hybrid Approach to Understanding Suicide in One First
      Nations' Collective.
AB  - Explanations for suicide are theorized primarily in terms of the individual,
      seldom considering the interdependent orientation of Indigenous communities.
      Drawing on the interpersonal theory of suicide and settler colonial theory, this
      study addresses Indigenous suicide on two levels: the individual and the
      collective. Twenty-one interviews were conducted with members of the Cowichan
      Tribes to understand reasons for suicide in one community. Qualitative analysis
      identified explanatory constructs proposed by the interpersonal theory as well as
      negative conditions stemming from colonialism, as proposed by settler colonial
      theory. These results argue that Indigenous suicidal behavior is best understood
      from an interdependent standpoint.

PMID- 28762558
TI  - Mycoplasma genitalium, an agent of reemerging sexually transmitted infections.
AB  - M. genitalium is a reemerging microorganism, responsible for sexually
      transmissible infections (STIs), with prevalence which varies depending on the
      country and population group studied. We report here M. genitalium prevalence
      among the specimens received for STI diagnosis in our routine microbiological
      laboratory in the university hospital in Marseille, France. We tested 4 624
      samples from 3 793 patients using qPCR for M. genitalium, C. trachomatis, N.
      gonorrheae, T. pallidum. Of these samples, 528 (13.6%) patients were tested
      positive for at least one pathogen and 126 (3.3%) were positive for M.
      genitalium. M. genitalium is the second most prevalent micro-organism detected in
      women after C. trachomatis (10.4%) and the third most prevalent in men after C.
      trachomatis (5.1%) and N. gonorrhoeae (4.4%). We observed no significant
      differences between the prevalence of M. genitalium in vaginal, urethral and
      urine specimens (p = 0.9). Prevalence of M. genitalium is significantly higher in
      patients aged between 10-30 years (4.1%) compared to those aged between 30 and 50
      years (2.7%) (p = 0.02, RR = 1.54 [1.06-2.24]) and patients over 50 years of age
      (1.1%) (p = 0.003, RR= 3.98 [1.47-10.8]). M. genitalium is a common agent of STI,
      therefore we suggest that this micro-organism should be systematically tested
      during chronic, recurrent, or antibiotic resistant genital infections and in
      populations at high-risk of STIs.

PMID- 28762559
TI  - Improvement of amphotericin B production by a newly isolated Streptomyces nodosus
      mutant.
AB  - Amphotericin B is an effective antifungal antibiotic. However, its production in
      the wild-type strain of Streptomyces nodosus is relatively low. In this study, a
      strain of ZJB 20130827, capable of producing amphotericin B, was isolated and
      identified as S. nodosus based on its physiological and biochemical
      characteristics as well as its 16S rRNA gene sequence analysis. With N-methyl-N
      nitroso-N'-nitroguanidine (NTG) and ultraviolet (UV) treatment, this wild-type
      strain was mutated for improving the yield of amphotericin B. After NTG and UV
      treatment, the best mutant N3 was obtained for optimization of fermentation
      conditions. The production of amphotericin B with N3 was 5,260 mg/L, while the
      wild-type strain ZJB 20130827 was about 580 mg/L, an increase of 906.9%. A
      genetically stable mutant strain with high yield of amphotericin B was obtained
      using NTG and UV. The mutant obtained in this work could potentially be utilized
      in industrial production of amphotericin B.

PMID- 28762556
TI  - NADPH oxidase 5 (NOX5)-induced reactive oxygen signaling modulates normoxic HIF
      1alpha and p27Kip1 expression in malignant melanoma and other human tumors.
AB  - NADPH oxidase 5 (NOX5) generated reactive oxygen species (ROS) have been
      implicated in signaling cascades that regulate cancer cell proliferation. To
      evaluate and validate NOX5 expression in human tumors, we screened a broad range
      of tissue microarrays (TMAs), and report substantial overexpression of NOX5 in
      malignant melanoma and cancers of the prostate, breast, and ovary. In human UACC
      257 melanoma cells that possesses high levels of functional endogenous NOX5,
      overexpression of NOX5 resulted in enhanced cell growth, increased numbers of
      BrdU positive cells, and increased gamma-H2AX levels. Additionally, NOX5
      overexpressing (stable and inducible) UACC-257 cells demonstrated increased
      normoxic HIF-1alpha expression and decreased p27Kip1 expression. Similarly,
      increased normoxic HIF-1alpha expression and decreased p27Kip1 expression were
      observed in stable NOX5-overexpressing clones of KARPAS 299 human lymphoma cells
      and in the human prostate cancer cell line, PC-3. Conversely, knockdown of
      endogenous NOX5 in UACC-257 cells resulted in decreased cell growth, decreased
      HIF-1alpha expression, and increased p27Kip1 expression. Likewise, in an
      additional human melanoma cell line, WM852, and in PC-3 cells, transient
      knockdown of endogenous NOX5 resulted in increased p27Kip1 and decreased HIF
      1alpha expression. Knockdown of endogenous NOX5 in UACC-257 cells resulted in
      decreased Akt and GSK3beta phosphorylation, signaling pathways known to modulate
      p27Kip1 levels. In summary, our findings suggest that NOX5 expression in human
      UACC-257 melanoma cells could contribute to cell proliferation due, in part, to
      the generation of high local concentrations of extracellular ROS that modulate
      multiple pathways that regulate HIF-1alpha and networks that signal through
      Akt/GSK3beta/p27Kip1 .

PMID- 28762560
TI  - Ambient mass spectrometry: Direct analysis of dimethoate, tebuconazole, and
      trifloxystrobin on olive and vine leaves by desorption electrospray ionization
      interface.
AB  - A new field of application for a relatively new mass-spectrometric interface such
      as desorption electrospray ionization was evaluated. For this purpose, its
      behavior was tested versus quantitative analysis of dimethoate, trifloxystrobin,
      and tebuconazole directly on olive and vine leaves surface. The goal was workers
      exposure assessment during field re-entry operations since evidence suggests an
      association between chronic occupational exposure to some agrochemicals and
      severe adverse effects. Desorption electrospray ionization gave good response
      working in positive ionization mode, while numerous test were necessary for the
      choice of a unique blend of spray solvents suitable for all 3 substances. The
      best compromise, in terms of signal to noise ratios, was obtained with the CH3
      OH/H2 O (80:20) mixture. The obvious difficulties related to the impossibility to
      use the internal standard were overcome through an accurate validation. Limits of
      detection and quantitation, dynamic ranges, matrix effects, and intraday
      precisions were calculated, and a small monitoring campaign was arranged to test
      method applicability and to evaluate potential dermal exposure. This protocol was
      developed in work safety field, but after a brief investigation, it was find to
      be suitable also for food residue evaluation.

PMID- 28762562
TI  - Co-expression of alpha-1 antitrypsin with cytoplasmic domain of v-SNARE in Pichia
      pastoris: Preserving biological activity of alpha-1 antitrypsin.
AB  - Alpha-1-antitrypsin (A1AT) is a major serum protein in human with protease
      inhibitory activity. Because of its extensive application in medicine,
      recombinant DNA technology has been considered for its production. The current
      study examines coexpression of A1AT and soluble domain of v-SNARE in Pichia
      pastoris, which can prevent the secretion of A1AT after thoroughly passing the
      secretory pathway. This was done mainly to preserve the biological activity of
      A1AT, which in the secretory mode might be impaired in the fermentation and early
      clarification conditions. SNARE proteins are the driving force for vesicle
      docking and membrane fusion in the exocytosis. Intracellular expression of the
      cytoplasmic domain of v-SNARE and its subsequent interaction to form SNARE
      complex can intensify the competition for A1AT secretory vesicles to be fused and
      released to the media. Our investigation shows successful coexpression of A1AT in
      the form of post-Golgi vesicles and the cytoplasmic domain of v-SNARE. Our
      findings confirmed the reduction of A1AT secretion by 45% caused accumulation of
      post-Golgi secretory vesicles filled with A1AT inside the yeast cell. A1AT
      trapped in secretory vesicles were biologically more active than secretory A1AT.
      These results indicate that the inhibition of A1AT secretion can protect its
      biological activity in fermentation and clarification processes.

PMID- 28762563
TI  - Femoral fracture type can be predicted from femoral structure: A finite element
      study validated by digital volume correlation experiments.
AB  - Proximal femoral fractures can be categorized into two main types: Neck and
      intertrochanteric fractures accounting for 53% and 43% of all proximal femoral
      fractures, respectively. The possibility to predict the type of fracture a
      specific patient is predisposed to would allow drug and exercise therapies, hip
      protector design, and prophylactic surgery to be better targeted for this patient
      rendering fracture preventing strategies more effective. This study hypothesized
      that the type of fracture is closely related to the patient-specific femoral
      structure and predictable by finite element (FE) methods. Fourteen femora were
      DXA scanned, CT scanned, and mechanically tested to fracture. FE-predicted
      fracture patterns were compared to experimentally observed fracture patterns.
      Measurements of strain patterns to explain neck and intertrochanteric fracture
      patterns were performed using a digital volume correlation (DVC) technique and
      compared to FE-predicted strains and experimentally observed fracture patterns.
      Although loaded identically, the femora exhibited different fracture types (six
      neck and eight intertrochanteric fractures). CT-based FE models matched the
      experimental observations well (86%) demonstrating that the fracture type can be
      predicted. DVC-measured and FE-predicted strains showed obvious consistency.
      Neither DXA-based BMD nor any morphologic characteristics such as neck diameter,
      femoral neck length, or neck shaft angle were associated with fracture type. In
      conclusion, patient-specific femoral structure correlates with fracture type and
      FE analyses were able to predict these fracture types. Also, the demonstration of
      FE and DVC as metrics of the strains in bones may be of substantial clinical
      value, informing treatment strategies and device selection and design. (c) 2017
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      36:993-1001, 2018.

PMID- 28762561
TI  - Diet-induced obesity causes visceral, but not subcutaneous, lymph node
      hyperplasia via increases in specific immune cell populations.
AB  - OBJECTIVES: The spatial proximity of adipose depots to secondary lymph nodes
      allows a unique relation between the two systems. Obesity, predominately visceral
      adiposity, links to numerous diseases; hence, we postulate that secondary
      lymphatics within this region contributes to disease risk. MATERIAL AND METHODS:
      Male C57BL/6 mice were fed standard CHOW (18% kcal fat) or Western diet (45% kcal
      fat) for 7 weeks. Visceral and subcutaneous lymph nodes and associated adipose
      depots they occupy were excised. Lymph node morphology and resident immune cell
      populations were characterized via histopathology, immunofluorescence and flow
      cytometry. Adipose tissue immune cell populations were also characterized.
      RESULTS: Obesity caused lymph node expansion, increased viable cell number and
      deviations in immune cell populations. These alterations were exclusive to
      visceral lymph nodes. Notably, pro-inflammatory antigen presenting cells and
      regulatory T cells increased in number in the visceral lymph node. Obesity,
      however, reduced T regulatory cells in visceral lymph nodes. The visceral adipose
      depot also had greater reactivity towards HFD than subcutaneous, with a greater
      percent of macrophages, dendritic and CD8+ T cells. Immune cell number, in both
      the visceral and subcutaneous, however decreased as adipose depots enlarged.
      CONCLUSION: Overall, HFD has a greater influence on visceral cavity than the
      subcutaneous. In the visceral lymph node, but not subcutaneous, HFD-induced
      obesity decreased cell populations that suppressed immune function while
      increasing those that regulate/activate immune response.

PMID- 28762564
TI  - Capsaicin-induced rapid neutrophil leukocyte activation in the rat urinary
      bladder microcirculatory bed.
AB  - AIMS: This study was initiated to investigate the involvement of neutrophil
      leukocyte activation in neurogenic inflammation, a process also involved in human
      urinary pathologies, elicited in the rat urinary bladder by the local
      administration of capsaicin, the archetypal TRPV1 agonist. The contribution of
      afferent nerves and sensory neuropeptides to leukocyte activation in the urinary
      bladder microcirculatory bed was examined. METHODS: Following a 15-min topical
      application of capsaicin (50 MUM), leukocyte-endothelial interactions were
      examined for an observation period of 45 min with intravital microscopy.
      Expression of adhesion molecules E-selectin and ICAM-1 implicated in these
      interactions was assessed by immunohistochemistry. Selective sensory denervation
      was performed by neonatal treatment with capsaicin. The role of the TRPV1
      receptor and two sensory neuropeptides (CGRP and substance P [SP]) were studied
      using the selective antagonists capsazepine, CGRP8-37 and RP67580, respectively.
      RESULTS: Capsaicin induced rapid increases in leukocyte rolling and adhesion and
      increased the expression of E-selectin and ICAM-1 in the postcapillary venules.
      Sensory chemodenervation via capsaicin and also TRPV1 receptor antagonism
      effectively prevented these changes. A similar reduction was observed in
      leukocyte adhesion after topical application of CGRP8-34 or RP67580, but only
      CGRP8-34 reduced the capsaicin-evoked leukocyte rolling. CONCLUSIONS: Topical
      application of capsaicin induces early neurogenically mediated cellular
      microcirculatory inflammatory reactions via the activation of the TRPV1 receptor
      and the release of CGRP and SP from sensory nerves in the bladder. Co
      administration of SP and CGRP receptor antagonists may ameliorate
      microcirculatory inflammatory changes elicited by capsaicin in the urinary
      bladder.

PMID- 28762565
TI  - Influence of lung volume on the interaction between cardiac output and
      cerebrovascular regulation during extreme apnoea.
AB  - NEW FINDINGS: What is the central question of this study? Does the reduction in
      cardiac output observed during extreme voluntary apnoea, secondary to high lung
      volume, result in a reduction in cerebral blood flow, perfusion pressure and
      oxygen delivery in a group of elite free divers? What is the main finding and its
      importance? High lung volumes reduce cardiac output and ventricular filling
      during extreme apnoea, but changes in cerebral blood flow are observed only
      transiently during the early stages of apnoea. This reveals that whilst cardiac
      output is important in regulating cerebral haemodynamics, the role of mean
      arterial pressure in restoring cerebral perfusion pressure is of greater
      significance to the regulation of cerebral blood flow. We investigated the role
      of lung volume-induced changes in cardiac output (Q) on cerebrovascular
      regulation during prolonged apnoea. Fifteen elite apnoea divers (one female; 185
      +/- 7 cm, 82 +/- 12 kg, 29 +/- 7 years old) attended the laboratory on two
      separate occasions and completed maximal breath-holds at total lung capacity
      (TLC) and functional residual capacity (FRC) to elicit disparate cardiovascular
      responses. Mean arterial pressure (MAP), internal jugular venous pressure and
      arterial blood gases were measured via cannulation. Global cerebral blood flow
      was quantified by ultrasound and cardiac output was quantified by via
      photoplethysmography. At FRC, stroke volume and Q did not change from baseline (P
      > 0.05). In contrast, during the TLC trial stroke volume and Q were decreased
      until 80 and 40% of apnoea, respectively (P < 0.05). During the TLC trial, global
      cerebral blood flow was significantly lower at 20%, but subsequently increased so
      that cerebral oxygen delivery was comparable to that during the FRC trial.
      Internal jugular venous pressure was significantly higher throughout the TLC
      trial in comparison to FRC. The MAP increased progressively in both trials but to
      a greater extent at TLC, resulting in a comparable cerebral perfusion pressure
      between trials by the end of apnoea. In summary, although lung volume has a
      profound effect on Q during prolonged breath-holding, these changes do not
      translate to the cerebrovasculature owing to the greater sensitivity of cerebral
      blood flow to arterial blood gases and MAP; regulatory mechanisms that facilitate
      the maintenance of cerebral oxygen delivery.

PMID- 28762566
TI  - Urodynamics in patients with spinal cord injury: A clinical review and best
      practice paper by a working group of The International Continence Society
      Urodynamics Committee.
AB  - AIMS: Urodynamics have been recommended and utilized in the evaluation of spinal
      cord injury (SCI) patients for many years, but there is no consensus on the
      optimal use and follow-up strategy for these patients. In the present manuscript,
      after reporting the available evidence, a working group of the Urodynamics
      Committee of the International Continence Society (ICS) provides the current
      knowledge and recommendations on patients' assessment, indications, role,
      technical aspects, and follow-up of urodynamic studies in SCI patients. METHODS:
      The working group has analyzed the current available evidence-based literature
      leading to a Delphi consensus formation by the members of the working group. A
      set of questions derived from the search were answered online on several
      occasions by an international panel of specialists. A 1-day face-to-face meeting
      of the experts finalized the discussion. Recommendations and expert opinions were
      finally reviewed by all the members of the ICS Urodynamics Committee on SCI core
      panel. RESULTS: Six experts participated in the four phases of the consensus
      process. Evidence was reviewed. There was substantial variability in the level
      and quality of detail reported across the literature yield. Several papers
      reported insufficient detail to allow synthesis of outcomes across studies. The
      findings of this preliminary review have been used to generate guidelines for
      best practice of urodynamics in SCI patients. The working group included
      recommendations for patients' pre-testing and urodynamic tests execution. Best
      practices were given as expert opinions where evidence was lacking. CONCLUSION:
      Urodynamic is highly recommended for patients with SCI after a proper initial
      assessment. Regular urodynamic follow-up is recommended to avoid upper urinary
      tract damage. However, until now, there is limited evidence on how frequently
      urodynamic control should be performed.

PMID- 28762567
TI  - Rotator cuff repair with a novel mesh suture: An ex vivo assessment of mechanical
      properties.
AB  - Surgical repair is a common treatment for rotator cuff tear; however, the retear
      rate is high. A high degree of suture repair strength is important to ensure
      rotator cuff integrity for healing. The purpose of this study was to compare the
      mechanical performance of rotator cuffs repaired with a mesh suture versus
      traditional polydioxanone suture II and FiberWire sutures in a canine in vitro
      model. Seventy-two canine shoulders were harvested. An infraspinatus tendon tear
      was created in each shoulder. Two suture techniques-simple interrupted sutures
      and two-row suture bridge-were used to reconnect the infraspinatus tendon to the
      greater tuberosity, using three different suture types: Mesh suture,
      polydioxanone suture II, or FiberWire. Shoulders were loaded to failure under
      displacement control at a rate of 20 mm/min. Failure load was compared between
      suture types and techniques. Ultimate failure load was significantly higher in
      the specimens repaired with mesh suture than with polydioxanone suture II or
      FiberWire, regardless of suture technique. There was no significant difference in
      stiffness among the six groups, with the exception that FiberWire repairs were
      stiffer than polydioxanone suture II repairs with the simple interrupted
      technique. All specimens failed by suture pull-out from the tendon. Based on our
      biomechanical findings, rotator cuff repair with the mesh suture might provide
      superior initial strength against failure compared with the traditional
      polydioxanone suture II or FiberWire sutures. Use of the mesh suture may provide
      increased initial fixation strength and decrease gap formation, which could
      result in improved healing and lower re-tear rates following rotator cuff repair.
      (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J
      Orthop Res 36:987-992, 2018.

PMID- 28762568
TI  - A new space of the face: The bucco-mandibular space.
AB  - Our previous studies based on intraoral dissection of fresh cadavers demonstrated
      the fissure and loose connective tissues behind the mucosa between the incisivus
      labii inferioris (ILI) and buccinator (BM) muscles. However, this raised new
      questions about the relationship among these muscles, the fissure and the buccal
      space. To our knowledge, no pathway to the oral cavity from the buccal space has
      been previously demonstrated, although such a pathway would better explain some
      routes of infection. Therefore, the aim of this study was to clarify the
      relationship among the mimetic muscles attached to the mandible, the fissure, and
      the buccal space. Twenty sides from 10 fresh frozen adult cadaveric Caucasian
      heads were used. The relationships among the ILI, BM, mandible, and buccal space
      were investigated with dissection and fluoroscopy. In all specimens, the fissure
      between the lateral border of the ILI and the anterior border of the BM formed
      the entrance of a space (here termed the bucco-mandibular space), which
      corresponded to the buccal mucosa in the premolar region. The superior border of
      this space was formed by the platysma and associated fascia, which was continuous
      with the masseteric fascia. This fascia clearly separated this space from the
      buccal space, which was located lateral to the BM and superior to this space.
      Clin. Anat. 30:958-962, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28762569
TI  - GA-Binding Protein Alpha Is Involved in the Survival of Mouse Embryonic Stem
      Cells.
AB  - Ets-related transcription factor GA-binding protein alpha (GABPalpha), which is
      encoded by Gabpa, is expressed in a variety of cell types and is involved in
      cellular functions such as cell cycle regulation, apoptosis, and differentiation.
      Here, we generated Gabpa conditional knockout embryonic stem cells (ESCs) and
      characterized its cellular phenotypes. Disruption of Gabpa revealed that the
      proliferation of Gabpa-null ESCs was drastically repressed and cells started to
      die within 2 days. The repressed proliferation of Gabpa-null ESCs was recovered
      by artificially forced expression of GABPalpha. Expression analysis showed that
      p53 mRNA levels were comparable; however, p53 target genes, including Cdkn1a/p21,
      Mdm2, and Gadd45a, were upregulated and cell cycle-related genes, including
      Cyclin D1/D2 and Cyclin E1/E2, were downregulated in Gabpa-null ESCs.
      Interestingly, p53 and cleaved Caspase3 expressions were enhanced in the cells
      and reduced proliferation as well as cell death of Gabpa-null ESCs were rescued
      by either transfection of p53 RNAi or treatment of the p53 inhibitor pifithrin
      alpha. These results suggest that GABPalpha inhibits the accumulation of p53 and
      is involved in the proliferation and survival of ESCs. Stem Cells 2017;35:2229
      2238.

PMID- 28762570
TI  - Streptococcal toxic shock syndrome occurring in the third trimester of pregnancy:
      A case report.
AB  - Group A streptococcal (GAS) toxic shock syndrome (TSS) is a rare life-threatening
      illness. Most reported cases have occurred in the post-partum period. Here, we
      report a rare case of a primigravid who developed GAS TSS in the third trimester.
      We also review the potential preventive measures and treatment modalities for
      this syndrome. A 29-year-old primigravid presented at 36 weeks' gestation with
      diarrhea, abdominal pain, fever, and fetal bradycardia. She underwent an
      emergency cesarean section and was subsequently diagnosed with GAS TSS. She had a
      complicated post-partum course marked by a 3-month hospital stay and major
      sequelae. Her infant died on post-partum day 4. GAS TSS should be considered in
      the differential diagnosis of pregnant patients presenting with fever and rapid
      onset of septic shock. A consideration to treat GAS that is detected incidentally
      during routine screening for group B streptococcus is suggested.

PMID- 28762571
TI  - Sex-specific differences in cardiovascular and metabolic hormones with integrated
      signalling in the paraventricular nucleus of the hypothalamus.
AB  - NEW FINDINGS: What is the topic of this review? We describe roles of crucial
      signalling molecules in the paraventricular nucleus of the hypothalamus and
      highlight recent data suggesting sex-specific changes in the expression of
      crucial signalling molecules and their receptors, which may underlie sex
      differences in both cardiovascular and metabolic function. What advances does it
      highlight? This review highlights the integrative capacity of the paraventricular
      nucleus in mediating cardiovascular and metabolic effects by integrating
      information from multiple signalling molecules. It also proposes that these
      signalling molecules have sex-specific differential gene expression, indicating
      the importance of considering these differences in our ongoing search to
      understand the female-male differences in the regulation of crucial autonomic
      systems. Many traditional cardiovascular hormones have been implicated in
      metabolic function. Conversely, many hormones traditionally involved in metabolic
      regulation have an effect on cardiovascular function. Many of these signalling
      molecules exert such effects through specific actions in the paraventricular
      nucleus, an integrative autonomic control centre located in the hypothalamus.
      Here, we focus on four cardiovascular/metabolic peptide hormones that signal
      within the paraventricular nucleus, namely angiotensin II, orexin, adiponectin
      and nesfatin-1. Each of these hormones has specific electrophysiological effects
      on paraventricular nucleus neurons that can be related to its physiological
      actions. In addition, we introduce preliminary transcriptomic data indicating
      that the genes for some of these hormones and their receptors have sex-specific
      differential expression.

PMID- 28762572
TI  - Promoting Effect of Ni(OH)2 on Palladium Nanocrystals Leads to Greatly Improved
      Operation Durability for Electrocatalytic Ethanol Oxidation in Alkaline Solution.
AB  - Most electrocatalysts for the ethanol oxidation reaction suffer from extremely
      limited operational durability and poor selectivity toward the C?C bond cleavage.
      In spite of tremendous efforts over the past several decades, little progress has
      been made in this regard. This study reports the remarkable promoting effect of
      Ni(OH)2 on Pd nanocrystals for electrocatalytic ethanol oxidation reaction in
      alkaline solution. A hybrid electrocatalyst consisting of intimately mixed
      nanosized Pd particles, defective Ni(OH)2 nanoflakes, and a graphene support is
      prepared via a two-step solution method. The optimal product exhibits a high mass
      specific peak current of >1500 mA mg-1Pd , and excellent operational durability
      forms both cycling and chronoamperometric measurements in alkaline solution. Most
      impressively, this hybrid catalyst retains a mass-specific current of 440 mA mg-1
      even after 20 000 s of chronoamperometric testing, and its original activity can
      be regenerated via simple cyclic voltammetry cycles in clean KOH. This great
      catalyst durability is understood based on both CO stripping and in situ
      attenuated total reflection infrared experiments suggesting that the presence of
      Ni(OH)2 alleviates the poisoning of Pd nanocrystals by carbonaceous
      intermediates. The incorporation of Ni(OH)2 also markedly shifts the reaction
      selectivity from the originally predominant C2 pathway toward the more desirable
      C1 pathway, even at room temperature.

PMID- 28762573
TI  - Evolution of defence cocktails: Antimicrobial peptide combinations reduce
      mortality and persistent infection.
AB  - The simultaneous expression of costly immune effectors such as multiple
      antimicrobial peptides is a hallmark of innate immunity of multicellular
      organisms, yet the adaptive advantage remains unresolved. Here, we test current
      hypotheses on the evolution of such defence cocktails. We use RNAi gene knock
      down to explore, the effects of three highly expressed antimicrobial peptides,
      displaying different degrees of activity in vitro against Staphylococcus aureus,
      during an infection in the beetle Tenebrio molitor. We find that a defensin
      confers no survival benefit but reduces bacterial loads. A coleoptericin
      contributes to host survival without affecting bacterial loads. An attacin has no
      individual effect. Simultaneous knock-down of the defensin with the other AMPs
      results in increased mortality and elevated bacterial loads. Contrary to common
      expectations, the effects on host survival and bacterial load can be independent.
      The expression of multiple AMPs increases host survival and contributes to the
      control of persisting infections and tolerance. This is an emerging property that
      explains the adaptive benefit of defence cocktails.

PMID- 28762574
TI  - A comparative study of brachial plexus sonography and magnetic resonance imaging
      in chronic inflammatory demyelinating neuropathy and multifocal motor neuropathy.
AB  - BACKGROUND AND PURPOSE: To compare the performance of neuroimaging techniques,
      i.e. high-resolution ultrasound (HRUS) and magnetic resonance imaging (MRI), when
      applied to the brachial plexus, as part of the diagnostic work-up of chronic
      inflammatory demyelinating neuropathy (CIDP) and multifocal motor neuropathy
      (MMN). METHODS: Fifty-one incident, treatment-naive patients with CIDP (n = 23)
      or MMN (n = 28) underwent imaging of the brachial plexus using (i) a standardized
      MRI protocol to assess enlargement or T2 hyperintensity and (ii) bilateral HRUS
      to determine the extent of nerve (root) enlargement. RESULTS: We found
      enlargement of the brachial plexus in 19/51 (37%) and T2 hyperintensity in 29/51
      (57%) patients with MRI and enlargement in 37/51 (73%) patients with HRUS.
      Abnormal results were only found in 6/51 (12%) patients with MRI and 12/51 (24%)
      patients with HRUS. A combination of the two imaging techniques identified 42/51
      (83%) patients. We found no association between age, disease duration or Medical
      Research Council sum-score and sonographic nerve size, MRI enlargement or
      presence of T2 hyperintensity. CONCLUSIONS: Brachial plexus sonography could
      complement MRI in the diagnostic work-up of patients with suspected CIDP and MMN.
      Our results indicate that combined imaging studies may add value to the current
      diagnostic consensus criteria for chronic inflammatory neuropathies.

PMID- 28762575
TI  - Changing trends in the etiology and management of vesicovaginal fistula.
AB  - Vesicovaginal fistula has remained a scourge and of public health importance,
      causing significant morbidity, and psychological and social problems to the
      patient. Continuous wetness, odor and discomfort cause serious social issues. The
      diagnosis has been traditionally based on clinical evaluation, dye testing,
      cystoscopic examination and contrast studies. A successful repair of such
      fistulas requires an accurate diagnosis and timely surgical intervention using
      techniques that are based on basic surgical principles with or without the use of
      interpositional flaps. The method of repair depends on the type and location of
      the fistula, and the surgeon's training and expertise. The main complications are
      recurrence and stress/urge incontinence. Prevention must include universal
      education, improvement in the social and nutritional status of women,
      discouraging early marriages, and the provision of improved accessible healthcare
      services.

PMID- 28762576
TI  - Mediastinal hydatidosis: Fine needle aspiration and liquid-based cytology.

PMID- 28762578
TI  - Identification and functionality prediction of pathogenesis-related protein 1
      from legume family.
AB  - The production and accumulation of pathogenesis-related (PR) proteins in plants
      is one of the important responses to biotic and abiotic stress. Large number of
      identified PR proteins has been categorized into 17 functional families based on
      their structure, phylogenetics, and biological activities. However, they are not
      widely studied in legume crops. Using 29 PR1 proteins from Arabidopsis thaliana,
      as query, here we have predicted 92 candidate PR1 proteins through the PSI-BLAST
      and HMMER programs. These candidate proteins were comprehensively analyzed with,
      multiple sequence alignment, domain architecture studies, signal peptide, and
      motif extraction followed by phylogenetic analysis. Further, response of two
      candidate PR1 proteins from chickpea against Fusarium oxysporum f.sp.ciceri
      attack was validated using qRT-PCR followed by their 3D structure prediction. To
      decipher mode of action for PR1s, docking of pathogen extracellular matrix
      components along with fungal elicitors was performed with two chickpea PR1
      proteins. Based on these findings, we propose carbohydrate to be the unique
      pathogen-recognition feature for PR1 proteins and beta-glucanase activity via
      beta-glucan binding or modification.

PMID- 28762577
TI  - Assessing barriers to adherence in routine clinical care for pediatric kidney
      transplant patients.
AB  - Patient-identified barriers to immunosuppressive medications are associated with
      poor adherence and negative clinical outcomes in transplant patients. Assessment
      of adherence barriers is not part of routine post-transplant care, and studies
      regarding implementing such a process in a reliable way are lacking. Using the
      Model for Improvement and PDSA cycles, we implemented a system to identify
      adherence barriers, including patient-centered design of a barriers assessment
      tool, identification of eligible patients, clear roles for clinic staff, and
      creating a culture of non-judgmental discussion around adherence. We performed
      time-series analysis of our process measure. Secondary analyses examined the
      endorsement and concordance of adherence barriers between patient-caregiver
      dyads. After three methods of testing, the most reliable delivery system was an
      EHR-integrated tablet that alerted staff of patient eligibility for assessment.
      Barriers were endorsed by 35% of caregivers (n=85) and 43% of patients (n=60).
      The most frequently patient-endorsed barriers were forgetting, poor taste, and
      side effects. Caregivers endorsed forgetting and side effects. Concordance
      between patient-caregiver dyads was fair (k=0.299). Standardized adherence
      barriers assessment is feasible in the clinical care of pediatric kidney
      transplant patients. Features necessary for success included automation,
      redundant systems with designated staff to identify and mitigate failures,
      aligned reporting structures, and reliable measurement approaches. Future studies
      will examine whether barriers predict clinical outcomes (eg, organ rejection,
      graft loss).

PMID- 28762579
TI  - Structure-Property Relationship Study of Donor and Acceptor 2,6-Disubstituted
      BODIPY Derivatives for High Performance Dye-Sensitized Solar Cells.
AB  - Seven donor and acceptor 2,6-disubstituted 4,4-difluoro-4-bora-3a,4a-diaza-s
      indacene (BODIPY) dyes have been synthesized and characterized. Including MPBTCA,
      which is a known compound, the seven BODIPY dyes have been characterized by
      varied physical methods, such as UV/Visible absorption spectroscopy, low energy
      photo-electron spectroscopy (AC-2), and HOMO-LUMO DFT/TDDFT calculation. All
      seven BODIPY dyes have absorption lambdamax around 535-545 nm, which is
      significantly longer than 499 nm of 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora
      3a,4a-diaza-s-indacene (PM 546). Having structural variation on donor group,
      acceptor group, donor pi-spacer, acceptor pi-spacer, and the substituent on
      boron, some BODIPY dyes exhibit small extinction coefficients or spectral
      integrals in solution (MPCtBTCA, MPBT-pyO, MPBTT-pyO, MTBTCA), broadening
      absorption spectral profile (MTBTCA), weak intramolecular charge transfer
      characteristics (MPBT-pyO, MPBTT-pyO, MTBTCA), too low LUMO energy level
      (PPBTCA), or insufficient dye-uptake by TiO2 FTO (MPBT-pyO, MPBTT-pyO, MTBTCA).
      Two of the seven BODIPY dyes, MPBTCA and MPBTTCA, do not show the adverse
      properties like other BODIPY dyes. With our improved TiO2 FTO (fluorine doped tin
      oxide) dyeing method, namely a solution dropping method, high performance dye
      sensitized solar cells (DSCs) have been realized by MPBTCA and MPBTTCA
      photosensitizers. Power conversion efficiencies of 6.3 and 6.4 % have been
      achieved by MPBTCA and MPBTTCA DSCs, respectively. To the best of our knowledge,
      MPBTCA and MPBTTCA are the most efficient dyes for the donor and acceptor 2,6
      disubstituted BODIPY DSCs so far.

PMID- 28762580
TI  - MnAl Layered Double Hydroxide Nanoparticles as a Dual-Functional Platform for
      Magnetic Resonance Imaging and siRNA Delivery.
AB  - Multifunctional nanoparticles for cancer theranosis have been widely explored for
      effective cancer detection and therapy. In this work, dually functionalised
      manganese-based layered double hydroxide nanoparticles (Mn-LDH) were examined as
      an effective anticancer drug/gene delivery system and for T1 -weighted magnetic
      resonance imaging (MRI) in brain cancer theranostics. Such Mn-LDH have been shown
      to accommodate dsDNA/siRNAs and efficiently deliver them to Neuro-2a cells (N2a).
      Mn-LDH have also shown high biocompatibility with low cytotoxicity. Importantly,
      the cell-death siRNA (CD-siRNA) delivered with Mn-LDH more efficiently kills
      brain cancer cells than the free CD-siRNA. Moreover, Mn-LDH can act as excellent
      contrast agents for MRI, with an r1 value of 4.47 mm-1  s-1 , which is even
      higher than that of commercial contrast agents based on Gd complexes (r1 =3.4 mm
      1  s-1 ). Altogether, the high delivery efficacy and MRI contrast capability make
      dual-functional Mn-LDH potential bimodal agents for simultaneous cancer diagnosis
      and therapy.

PMID- 28762581
TI  - Remote detection of explosives using field asymmetric ion mobility spectrometer
      installed on multicopter.
AB  - The detection of explosives and drugs in hard-to-reach places is a considerable
      challenge. We report the development and initial experimental characterization of
      the air analysis system that includes Field Asymmetric Ion Mobility Spectrometer,
      array of the semiconductor gas sensors and is installed on multicopter. The
      system was developed based on the commercially available DJI Matrix 100 platform.
      For data collection and communication with operator, the special compact computer
      (Intel Compute Stick) was installed onboard. The total weight of the system was
      3.3 kg. The system allows the 15-minute flight and provides the remote access to
      the obtained data. The developed system can be effectively used for the detection
      of impurities in the air, ecology monitoring, detection of chemical warfare
      agents, and explosives, what is especially important in light of recent
      terroristic attacks. The capabilities of the system were tested on the several
      explosives such as trinitrotoluene and nitro powder.

PMID- 28762582
TI  - Detection of homozygous deletions in tumor-suppressor genes ranging from dozen to
      hundreds nucleotides in cancer models.
AB  - Tumor-suppressor genes can be inactivated by several mechanisms and, in a
      majority of cases, both alleles need to be affected. One of the mechanisms of
      inactivation is due to deletions ranging from dozen to hundreds of nucleotides;
      such deletions are often missed by variant callers. HomDelDetect is a method to
      detect such homozygous deletions in cancer models, such as cancer cell lines and
      potentially patient tumor-derived xenografts. This method can be applied to
      partial exome, whole-exome sequencing, whole-genome sequencing, and RNA-seq data.
      We applied our method across a panel of CCLE cancer cell lines and observed good
      concordance with SNP array-based analysis and also detected deletions that have
      been missed by variant callers and by SNP arrays, demonstrating the ability of
      HomDelDetect to improve the annotations of tumor-suppressor genes in cancer
      models.

PMID- 28762583
TI  - Case of spontaneous splenic rupture caused by ectopic pregnancy in the spleen.
AB  - Splenic ectopic pregnancy refers to the implantation of the oosperm in the
      spleen. If not diagnosed early, the results of this phenomenon would almost
      certainly be splenic rupture, which is equivalent to the spontaneous rupture of
      the spleen. If the patient has no history of trauma, it is difficult to diagnose
      this condition early and an explicit diagnosis is often obtained by exploratory
      laparotomy. We report the case of a 27-year-old woman who was admitted to the
      hospital due to abdominal pain and hemorrhagic shock. Under emergency general
      anesthesia, gynecologist and hepatobiliary surgeons worked together to conduct an
      exploratory laparotomy. It was confirmed during surgery that this was ectopic
      pregnancy in the spleen, which caused rupture of the spleen. Hence, splenectomy
      was conducted. Postoperative recovery was good.

PMID- 28762584
TI  - Drug-related stigma and access to care among people who inject drugs in Vietnam.
AB  - INTRODUCTION AND AIMS: There are considerable challenges faced by people with a
      history of injecting drug use (PWID) in Vietnam, including drug-related stigma
      and lack of access to healthcare. Seeking and utilising healthcare, as well as
      harm reduction programs for PWID, are often hampered by drug-related stigma. This
      study aimed to examine the impacts of drug-related stigma on access to care and
      utilisation of harm reduction programs among PWID in Vietnam. DESIGN AND METHODS:
      A cross-sectional study was conducted in two provinces in Vietnam, Phu Tho and
      Vinh Phuc. The study participants completed the survey by using Audio Computer
      Assisted Self-Interview between late 2014 and early 2015. Linear multiple
      regression models and logistic regression models were used to assess the
      relationship among drug-related stigma, access to care and utilisation of harm
      reduction programs, including methadone maintenance treatment (MMT) and needle
      exchange programs (NEP). RESULTS: A total of 900 PWID participated in this study.
      Drug-related stigma was significantly associated with lower level of access to
      care, but not with utilisation of MMT or NEP. Older age was positively associated
      with higher levels of access to care. Levels of education were positively
      correlated with access to care, as well as utilisation of MMT and NEP. DISCUSSION
      AND CONCLUSIONS: This study underscores the need for future interventions to
      reduce drug-related stigma in society and in health-care settings to improve
      PWID's utilisation of care services. Special attention should be paid to younger
      PWID and those with lower levels of education.

PMID- 28762585
TI  - Therapeutic Effects of 6-Gingerol, 8-Gingerol, and 10-Gingerol on Dextran Sulfate
      Sodium-Induced Acute Ulcerative Colitis in Rats.
AB  - Ulcerative colitis is one of the most common types of inflammatory bowel disease
      and is multifactorial and relapsing. 6-Gingerol, a component of gingerols
      extracted from ginger (Zingiber officinale), has been reported to improve
      ulcerative colitis. The present study aims to investigate the therapeutic
      efficacy of two analogous forms of 6-gingerol, 8-gingerol, and 10-gingerol, on
      ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v)
      dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8
      gingerol, and 10-gingerol were then given intraperitoneally at doses of 30 mg kg
      1  d-1 for another 7 days, respectively. Body weight change, disease activity
      index, inflammatory cytokines, and oxidative stress indices were measured, and
      the colonic tissue injuries were assessed macroscopically and
      histopathologically. Results showed that all three gingerols attenuated colitic
      symptoms evoked by dextran sulfate sodium, significantly elevated superoxide
      dismutase activity, decreased malondialdehyde levels and myeloperoxidase activity
      in the colon tissue, and markedly reduced the content of tumor necrosis factor
      alpha and Interleukin 1 beta in the serum. Histological observations showed that
      all three gingerols obviously accelerated mucosal damage healing. It is concluded
      that 6-gingerol, 8-gingerol, and 10-gingerol, the three analogues, have a strong
      and relatively equal efficacy in the treatment of colitis. Copyright (c) 2017
      John Wiley & Sons, Ltd.

PMID- 28762586
TI  - Complete auxotrophy for unsaturated fatty acids requires deletion of two sets of
      genes in Mycobacterium smegmatis.
AB  - The synthesis of unsaturated fatty acids in Mycobacterium smegmatis is poorly
      characterized. Bioinformatic analysis revealed four putative fatty acid
      desaturases in its genome, one of which, MSMEG_1886, is highly homologous to
      desA3, the only palmitoyl/stearoyl desaturase present in the Mycobacterium
      tuberculosis genome. A MSMEG_1886 deletion mutant was partially auxotrophic for
      oleic acid and viable at 37 degrees C and 25 degrees C, although with a long lag
      phase in liquid medium. Fatty acid analysis suggested that MSMEG_1886 is a
      palmitoyl/stearoyl desaturase, as the synthesis of palmitoleic acid was
      abrogated, while oleic acid contents dropped by half in the mutant. Deletion of
      the operon MSMEG_1741-1743 (highly homologous to a Pseudomonas aeruginosa acyl
      CoA desaturase) had little effect on growth of the parental strain; however the
      double mutant MSMEG_1886-MSMEG_1741-1743 strictly required oleic acid for growth.
      The DeltaMSMEG_1886-DeltaMSMEG_1741 double mutant was able to grow (poorly but
      better than the DeltaMSMEG_1886 single mutant) in solid and liquid media devoid
      of oleic acid, suggesting a repressor role for DeltaMSMEG_1741. Fatty acid
      analysis of the described mutants suggested that MSMEG_1742-43 desaturates C18:0
      and C24:0 fatty acids. Thus, although the M. smegmatis desA3 homologue is the
      major player in unsaturated fatty acid synthesis, a second set of genes is also
      involved.

PMID- 28762587
TI  - Synthesis, Isolation, and Trifluoromethylation of Two Isomers of C84 -Based
      Monometallic Cyanide Clusterfullerenes: Interplay between the Endohedral Cluster
      and the Exohedral Addends.
AB  - As an emerging member of endohedral fullerenes, metal cyanide clusterfullerenes
      (CYCF) are unique in terms of the encapsulation of a monometallic cluster. To
      date the reported carbon cages of CYCFs are limited to C82 and C76 , and little
      is known about the chemical reactivity of CYCFs. Herein, two isomers of the first
      C84 -based CYCFs, YCN@C84 , were isolated as trifluoromethyl derivatives,
      including YCN@C84 (23)(CF3 )18 and three isomers of YCN@C84 (13)(CF3 )16 , which
      are based on a unique chiral C2 -C84 (13) cage. As a common feature of the CF3
      addition patterns, the YCN@C84 (CF3 )16/18 compounds are stabilized by the
      formation of isolated C=C bonds and benzenoid rings on the carbon cages. The
      interplay between the endohedral YCN cluster and the exhohedral CF3 addends was
      unveiled according to single-crystal X-ray diffraction studies, thus offering new
      insight into the chemical reactivity of CYCFs.

PMID- 28762588
TI  - An investigation of shock wave therapy and low-intensity pulsed ultrasound on
      fracture healing under reduced loading conditions in an ovine model.
AB  - The use of shock wave therapy (SWT) and low-intensity pulsed ultrasound (LIPUS)
      as countermeasures to the inhibited fracture healing experienced during
      mechanical unloading was investigated by administering treatment to the fracture
      sites of mature, female, Rambouillet Columbian ewes exposed to partial mechanical
      unloading or full gravitational loading. The amount of fracture healing
      experienced by the treatment groups was compared to controls in which identical
      surgical and testing protocols were administered except for SWT or LIPUS
      treatment. All groups were euthanized after a 28-day healing period. In vivo
      mechanical measurements demonstrated no significant alteration in fixation plate
      strains between treatments within either partial unloading group. Similarly, DXA
      BMD and 4-point bending stiffness were not significantly altered following either
      treatment. MUCT analyses demonstrated lower callus bone volume for treated
      animals (SWT and LIPUS, p < 0.01) in the full gravity group but not between
      reduced loading groups. Callus osteoblast numbers as well as mineralized surface
      and bone formation rate were significantly elevated to the level of the full
      gravity groups in the reduced loading groups following both SWT and LIPUS.
      Although no increase in 4-week mechanical strength was observed, it is possible
      that an increase in the overall rate of fracture healing (i.e., callus strength)
      may be experienced at longer time points under partial loading conditions given
      the increase in osteoblast numbers and bone formation parameters following SWT
      and LIPUS. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals,
      Inc. J Orthop Res 36:921-929, 2018.

PMID- 28762589
TI  - Factors influencing parenting efficacy of Asian immigrant, first-time mothers: A
      cross-sectional, correlational survey.
AB  - In this study, we determined the factors influencing parenting efficacy of Asian
      immigrant, first-time mothers. The research design was a cross-sectional,
      correlational study. The study included 125 first-time mothers who immigrated and
      married Korean men, and were living in Korea. Data were collected using
      translated questionnaires, and analyzed for descriptive statistics, Pearson
      correlation, and multiple regression analysis. The major finding was that the
      parenting efficacy of immigrant women was influenced by childcare support from
      their husbands, maternal identity, and original nationality. The findings suggest
      that customized programs be developed and used to enhance parenting efficacy for
      Asian immigrant, first-time mothers. In developing such programs, the advantages
      of maternal identity, social support from the husband, and women's cultural
      context should be considered.

PMID- 28762590
TI  - Contributions of insects and droughts to growth decline of trembling aspen mixed
      boreal forest of western Canada.
AB  - Insects, diseases, fire and drought and other disturbances associated with global
      climate change contribute to forest decline and mortality in many parts of the
      world. Forest decline and mortality related to drought or insect outbreaks have
      been observed in North American aspen forests. However, little research has been
      done to partition and estimate their relative contributions to growth declines.
      In this study, we combined tree-ring width and basal area increment series from
      40 trembling aspen (Populus tremuloides Michx.) sites along a latitudinal
      gradient (from 52 degrees  to 58 degrees N) in western Canada and attempted to
      investigate the effect of drought and insect outbreaks on growth decline, and
      simultaneously partition and quantify their relative contributions. Results
      indicated that the influence of drought on forest decline was stronger than
      insect outbreaks, although both had significant effects. Furthermore, the
      influence of drought and insect outbreaks showed spatiotemporal variability. In
      addition, our data suggest that insect outbreaks could be triggered by warmer
      early spring temperature instead of drought, implicating that potentially
      increased insect outbreaks are expected with continued warming springs, which may
      further exacerbate growth decline and death in North America aspen mixed forests.

PMID- 28762591
TI  - EAN consensus review on prevention, diagnosis and management of tick-borne
      encephalitis.
AB  - BACKGROUND AND PURPOSE: Tick-borne encephalitis (TBE) is an infection of the
      central nervous system (CNS) caused by tick-borne encephalitis virus (TBEV) and
      transmitted by ticks, with a variety of clinical manifestations. The incidence of
      TBE in Europe is increasing due to an extended season of the infection and the
      enlargement of endemic areas. Our objectives are to provide recommendations on
      the prevention, diagnosis and management of TBE, based on evidence or consensus
      decisions. METHODS: For systematic evaluation, the literature was searched from
      1970 to 2015 (including early online publications of 2016), and recommendations
      were based on evidence or consensus decisions of the Task Force when evidence
      based data were not available. RECOMMENDATIONS: Vaccination against TBE is
      recommended for all age groups above 1 year in highly endemic areas (>=5
      cases/100 000/year), but also for individuals at risk in areas with a lower
      incidence. Travellers to endemic areas should be vaccinated if their visits will
      include extensive outdoor activities. Post-exposure prophylaxis after a tick bite
      is not recommended. A case of TBE is defined by the presence of clinical signs of
      meningitis, meningoencephalitis or meningoencephalomyelitis with cerebrospinal
      fluid (CSF) pleocytosis (>5 * 106 cells/l) and the presence of specific TBEV
      serum immunoglobulin M (IgM) and IgG antibodies, CSF IgM antibodies or TBEV IgG
      seroconversion. TBEV-specific polymerase chain reaction in blood is diagnostic in
      the first viremic phase but it is not sensitive in the second phase of TBE with
      clinical manifestations of CNS inflammation. Lumbar puncture should be performed
      in all patients with suspected CNS infection unless there are contraindications.
      Imaging of the brain and spinal cord has a low sensitivity and a low specificity,
      but it is useful for differential diagnosis. No effective antiviral or
      immunomodulating therapy is available for TBE; therefore the treatment is
      symptomatic. Patients with a potentially life threatening meningoencephalitis or
      meningoencephalomyelitis should be admitted to an intensive care unit. In the
      case of brain oedema, analgosedation should be deepened; osmotherapy and
      corticosteroids are not routinely recommended. If intracranial pressure is
      increased, therapeutic hypothermia or decompressive craniectomy might be
      considered. Seizures should be treated as any other symptomatic epileptic
      seizures. CONCLUSIONS: Tick-borne encephalitis is a viral CNS infection that may
      result in long-term neurological sequelae. Since its incidence in Europe is
      increasing due to broadening of endemic areas and prolongation of the tick
      activity season, the health burden of TBE is enlarging. There is no effective
      antiviral treatment for TBE, but the disease may be effectively prevented by
      vaccination.

PMID- 28762592
TI  - Effect of intragastric FODMAP infusion on upper gastrointestinal motility,
      gastrointestinal, and psychological symptoms in irritable bowel syndrome vs
      healthy controls.
AB  - BACKGROUND: The low fermentable oligo-, di-, mono-saccharides and polyol (FODMAP)
      diet is a treatment strategy to reduce symptoms of irritable bowel syndrome
      (IBS). Acute effects of FODMAPs on upper gastrointestinal motility are
      incompletely understood. Our objectives were to assess the acute effects of
      intragastric FODMAP infusions on upper gastrointestinal motility and
      gastrointestinal and psychological symptoms in healthy controls (HC) and IBS
      patients. METHODS: A high-resolution solid-state manometry probe and an infusion
      tube were positioned into the stomach. Fructans, fructose, FODMAP mix, or glucose
      was intragastrically administered to HC, and fructans or glucose was administered
      to IBS patients until full satiation (score 0-5), in a randomized crossover
      fashion. Manometric measurements continued for 3 hours. Gastrointestinal and
      psychological symptoms were assessed by questionnaires at predefined time points.
      The study was registered on www.clinicaltrials.gov (NCT02980406). KEY RESULTS:
      Twenty HC and 20 IBS patients were included. Fructans induced higher postprandial
      gastric pressures compared with glucose over both groups (P<.001). Bloating,
      belching, and pain increased more in IBS over both carbohydrates (P<.041). In
      addition, IBS patients reported more flatulence and cramps compared with HC
      following fructans (P<.001). Glucose induced more fatigue and dominance compared
      with fructans (P=.028, P=.001). Irritable bowel syndrome patients reported a
      higher increase in anger (P=.030) and a stronger decrease in positive affect
      (P=.021). CONCLUSIONS & INFERENCES: The upper gastrointestinal motility response
      varies between carbohydrates. Irritable bowel syndrome patients are more
      sensitive to fructan infusion, reflected in their higher gastrointestinal symptom
      scores. Acute carbohydrate infusion can have differential psychological effects
      in IBS and HC.

PMID- 28762593
TI  - Influencing everyday activities in a nursing home setting: A call for ethical and
      responsive engagement.
AB  - This study focuses on influence that older adults, living in nursing homes, have
      over everyday activities. Everyday activities are key to sustain a sense of
      stability, predictability, and enjoyment in the local world of people's everyday
      and therefore a critical dimension of the person-centeredness framework applied
      within gerontology. This narrative ethnographic study aimed to shed light on how
      influence can be situated contextually, and how it can emerge through activities
      as well as how it is negotiated in everyday by frail older adults living in a
      nursing home. Residents, staff members, and significant others from one nursing
      home in an urban area of Sweden participated in this study. Data were gathered
      through fieldwork, including participant observation and formal and informal
      conversations during a period of 6 months. Data were analyzed through a narrative
      interpretative approach. The findings are presented in narrative form as
      exemplars. The exemplars-Craquelures as justification, Seeking a place for other
      life worlds and An almost perfect trip-reveal a gap between the client
      centeredness framework and lived experiences regarding older adults' influence in
      everyday activities. The role of everyday activities in the context of frailty is
      discussed in terms of ethical and responsive engagement, and implications for
      health-care practices are considered.

PMID- 28762594
TI  - Evaluation of outpatient therapeutic programme (OTP) for treatment of severe
      acute malnutrition in Yemen: a focus on treatment default and its risk factors.
AB  - OBJECTIVES: This study aimed to measure the treatment default rate among children
      with severe acute malnutrition (SAM) who were admitted to the outpatient
      therapeutic programme (OTP) in Yemen and determine its risk factors. METHODS: A
      prospective study was conducted among children with SAM who were newly admitted
      to the 11 OTPs in primary health centres of Sana'a city. A pretested
      semistructured questionnaire was used for data collection at admission and at
      after 2 months of admission to the OTP. Univariate and multivariate analysis
      using binary logistic regression were used to analyse the risk factors of
      treatment default. RESULTS: This study included 339 SAM children. Of those, 186
      (55%) children discharged as defaulters, 141 (42%) were cured, and 12 (3%) were
      transferred to other treatment sites. Many factors related to poor accessibility,
      poor satisfaction with staff and system, and treatment and acceptability of OTP
      services factors were significantly associated with treatment default. Having
      difficulty to attend OTP every week (OR 8.4), unavailability of medication during
      follow-up visits (OR 5.0), not liking to eat Plumpy'Nut (OR 5.8), and not gaining
      weight since the start of treatment (OR 9.3) were the strongest predictors of
      treatment default. CONCLUSIONS: This study showed a high default rate among SAM
      children in Sana'a city. Factors related to poor accessibility, poor satisfaction
      with staff and system, and factors related to treatment and acceptability of OTP
      services were significantly associated with high default rate. Expansion of OTP
      services and training OTPs staff on SAM treatment protocols are highly
      recommended.

PMID- 28762596
TI  - Effectiveness of home-based exercise in older patients with advanced chronic
      obstructive pulmonary disease: A 3-year cohort study.
AB  - AIM: To determine whether home-based exercise can improve clinical outcomes in
      older patients with advanced chronic obstructive pulmonary disease using long
      term oxygen therapy. METHODS: Information was provided to improve chronic
      obstructive pulmonary disease self-management before the onset of the present
      prospective 3-year cohort study. Patients selected either home-based exercise
      using a lower-limb cycle machine (ergo-bicycle; group E), or usual exercise
      (group U). To assess self-management, the Lung Information Needs Questionnaire
      was evaluated every 6 months. Clinical outcomes included the 6-min walk test,
      pulmonary function tests, the body mass index, airflow obstruction, dyspnea and
      exercise index, St. George's respiratory questionnaire, and the number of
      exacerbations and hospitalizations. RESULTS: A total of 136 patients (group E =
      72; group U = 64), with a mean age of 74.2 years were enrolled. Total Lung
      Information Needs Questionnaire scores improved over 3 years for group E (P =
      0.003). The distance of the 6-min walk test was well maintained in group E, but
      significantly decreased in group U (P < 0.001). The percentage of forced
      expiratory volume in 1 s at baseline was lower in group E (P = 0.016), but was
      maintained over 3 years, whereas a significant reduction was seen in group U (P =
      0.001). The body mass index, airflow obstruction, dyspnea and exercise index
      significantly worsened in both groups over 3 years (group E: P = 0.011; group U:
      P < 0.001), whereas a significant decrease in the number of exacerbations was
      noted in group E (P = 0.009). CONCLUSIONS: Patients who undertook home-based
      exercise using an ergo-bicycle were able to maintain clinical outcomes including
      6-min walk test distance and percentage of forced expiratory volume in 1 s
      predicted, and recorded fewer exacerbations over 3 years. Geriatr Gerontol Int
      2018; 18: 42-49.

PMID- 28762595
TI  - Perinatal high fat diet increases inhibition of dorsal motor nucleus of the vagus
      neurons regulating gastric functions.
AB  - BACKGROUND: Previous studies suggest an increased inhibition of dorsal motor
      nucleus of the vagus (DMV) neurons following exposure to a perinatal high fat
      diet (PNHFD); the underlying neural mechanisms, however, remain unknown. This
      study assessed the effects of PNHFD on inhibitory synaptic inputs to DMV neurons
      and the vagally dependent control of gastric tone and motility. METHODS: Whole
      cell patch clamp recordings were made from DMV neurons in thin brainstem slices
      from Sprague-Dawley rats fed either a control diet or HFD (14 or 60% kcal from
      fat, respectively) from embryonic day 13 onwards; gastric tone and motility were
      recorded in in vivo anesthetized rats. KEY RESULTS: The non-selective GABAA
      antagonist, BIC (10 MUmol L-1 ), induced comparable inward currents in PNHFD and
      control DMV neurons, but a larger current in PNHFD neurons at higher
      concentrations (50 MUmol L-1 ). Differences were not apparent in neuronal
      responses to the phasic GABAA antagonist, gabazine (GBZ), the extrasynaptic GABAA
      agonist, THIP, the GABA transport blocker, nipecotic acid, or the gliotoxin,
      fluoroacetate, suggesting that PNHFD altered inhibitory transmission but not
      GABAA receptor density or function, GABA uptake or glial modulation of synaptic
      strength. Similarly, the increase in gastric motility and tone following
      brainstem microinjection of low doses of BIC (1-10 pmoles) and GBZ (0.01-0.1
      pmoles) were unchanged in PNHFD rats while higher doses of BIC (25 pmoles)
      induced a significantly larger increase in gastric tone compared to control.
      CONCLUSIONS AND INFERENCES: These studies suggest that exposure to PNHFD
      increases the tonic inhibition of DMV neurons, possibly contributing to
      dysregulated vagal control of gastric functions.

PMID- 28762597
TI  - Visfatin mediates doxorubicin resistance in human non-small-cell lung cancer via
      Akt-mediated up-regulation of ABCC1.
AB  - OBJECTIVES: Non-small-cell lung cancer (NSCLC) is one of the leading causes of
      cancer deaths worldwide. Increasing levels of visfatin are correlated with worse
      clinical prognosis of NSCLC. However, the effects of visfatin on drug resistant
      are still not well illustrated. MATERIALS AND METHODS: Effects of visfatin on
      drug resistant cells were checked by CCK-8 kit. Gene and protein variations were
      measured by real-time PCR and western blot analysis, respectively. RESULTS: Our
      present data confirmed that expression of visfatin was significantly increased in
      NSCLC cells and tissues. In addition, protein and mRNA expression of visfatin
      were significantly elevated in doxorubicin (Dox) resistance of NSCLC cells when
      compared with their corresponding sensitivity parental cells. Overexpression of
      visfatin can down-regulate the Dox sensitivity of NSCLC cells and up-regulate the
      mRNA and protein expression of ABCC1, while has no effect on ABCB1. Knockdown of
      visfatin can down-regulate the expression of ABCC1 in Dox-resistant NSCLC cells.
      Visfatin can increase the phosphorylation and nuclear localization of Akt in
      NSCLC cells. LY294002 can decrease the expression of multidrug resistance protein
      1 (MRP1) in NSCLC Dox-resistant cells. Chromatin immunoprecipitation assays
      showed that overexpression of visfatin can significantly increase the binding of
      Akt with the promoter of ABCC1 in both A549 and H1793 cells. CONCLUSIONS: These
      data showed that visfatin can decrease Dox sensitivity of NSCLC cells via
      activation of Akt/MRP1. It indicated that inhibition of visfatin signals might be
      a promising therapeutic strategy for the management of chemoresistance of NSCLC
      patients.

PMID- 28762598
TI  - Heteranthery as a solution to the demand for pollen as food and for pollination -
      Legitimate flower visitors reject flowers without feeding anthers.
AB  - Heteranthery, the presence of feeding and pollinating anthers in the same flower,
      seems to mediate the evolutionary dilemma for plants to protect their gametes and
      yet provide food for pollinators. This study aims to elucidate the role of
      heteranthery in the buzz-pollinated Senna reniformis. The fecundity of pollen
      from long-, medium- and short-sized anthers was determined by hand cross
      pollination experiments, and the quantity, size, ornamentation and viability of
      pollen of different anthers were compared. Rates of flower rejection by bees were
      measured in anther removal experiments to assess the preferences of flower
      visitors for feeding or pollinating anthers. Large bees, which were the effective
      pollinators of self-incompatible S. reniformis, avoided flowers without short
      feeding anthers, but not those without medium or long anthers. Illegitimate small
      and medium-sized bees were unresponsive to anther exclusion experiments. Long
      anthers deposited pollen on the back and short anthers on the venter of large
      bees. Pollen from long anthers had higher in vitro viability and higher fruit and
      seed set after cross-pollination than pollen from other sized anthers. Short
      anthers produce feeding pollen to effective pollinators and long anthers are
      related to pollination of S. reniformis. Bee behaviour and size was found to
      directly influence the role of anthers in the 'division of labour'. Only large
      bee pollinators that carry the pollinating pollen from long anthers in 'safe
      sites' associated short anthers with the presence of food. In the absence of
      these larger bee pollinators, the role of heteranthery in S. reniformis would be
      strongly compromised and its function would be lost.

PMID- 28762599
TI  - Diversity of progesterone action on lipopolysaccharide-induced expression changes
      in cultured human cervical fibroblasts according to inflammation and treatment
      timing.
AB  - PROBLEM: The effectiveness of progesterone (P4) treatment for preventing preterm
      births is unclear. Its effects on the uterine cervix were tested using cultured
      human uterine cervical fibroblasts (UCFs). METHOD OF STUDY: UCFs were incubated
      with lipopolysaccharide (LPS) in the presence or absence of P4 under various
      conditions. mRNA was subjected to PCR arrays and real-time RT-PCR to assess IL-6,
      IL-8, IL-1beta, PTGS2, MMP-1, and CXCL10 expression. RESULTS: When exposed to a
      high-LPS concentration (2.0 MUg/mL), expression of these genes was not suppressed
      by simultaneous P4 (1.0 MUmol/L) treatment, but it was significantly inhibited
      when P4 was administered 1 hour prior to LPS, with the exception of the
      chemokines IL-8 and CXCL10. Expression of all genes was restricted by P4 under
      low-level LPS (0.2 MUg/mL) stimulation, especially when administered prior to LPS
      treatment. CONCLUSION: These data suggest that early or prophylactic P4
      administration is an effective and important measure for reducing preterm birth
      risk.

PMID- 28762600
TI  - Assessing the practice of palliative care doctors: what driving advice do they
      give patients with advanced disease?
AB  - BACKGROUND: There is little research and no clear guidelines for clinicians to
      follow when instructing patients with advanced disease about driving. AIMS: To
      investigate current practice in providing advice to patients with advanced
      disease and identify areas of consensus or variation with the Australian driving
      guidelines. METHODS: An online survey was distributed to Australian members of
      the Australian and New Zealand Society of Palliative Medicine. Responses were
      analysed using descriptive statistics. RESULTS: The survey was distributed to 322
      Australian and New Zealand Society of Palliative Medicine members and received 92
      responses (29% response rate). Most respondents were aware of the driving
      guidelines (76%) and about half of the respondents had read the driving
      guidelines (55%). The majority of respondents had been asked to provide advice
      about driving to their patient or patient's caregiver (91%). Most respondents had
      asked a patient to stop driving (94%), but only 27% had reported a patient to the
      Driver Licensing Authority. Only 14% of respondents were in consensus with the
      guidelines in providing driving advice to a patient with asymptomatic brain
      metastases. Most doctors (64%) advise patients to refrain temporarily from
      driving post-short-acting oral morphine, with 4 h (36%) being the most common
      time period for not driving. CONCLUSIONS: This is the first survey investigating
      the practice of Australian doctors in assessing fitness to drive of patients with
      advanced disease. The survey found wide variability in practice and substantial
      discordance with current driving guidelines.

PMID- 28762601
TI  - Natural acidification changes the timing and rate of succession, alters community
      structure, and increases homogeneity in marine biofouling communities.
AB  - Ocean acidification may have far-reaching consequences for marine community and
      ecosystem dynamics, but its full impacts remain poorly understood due to the
      difficulty of manipulating pCO2 at the ecosystem level to mimic realistic
      fluctuations that occur on a number of different timescales. It is especially
      unclear how quickly communities at various stages of development respond to
      intermediate-scale pCO2 change and, if high pCO2 is relieved mid-succession,
      whether past acidification effects persist, are reversed by alleviation of pCO2
      stress, or are worsened by departures from prior high pCO2 conditions to which
      organisms had acclimatized. Here, we used reciprocal transplant experiments along
      a shallow water volcanic pCO2 gradient to assess the importance of the timing and
      duration of high pCO2 exposure (i.e., discrete events at different stages of
      successional development vs. continuous exposure) on patterns of colonization and
      succession in a benthic fouling community. We show that succession at the
      acidified site was initially delayed (less community change by 8 weeks) but then
      caught up over the next 4 weeks. These changes in succession led to
      homogenization of communities maintained in or transplanted to acidified
      conditions, and altered community structure in ways that reflected both short-
      and longer-term acidification history. These community shifts are likely a result
      of interspecific variability in response to increased pCO2 and changes in species
      interactions. High pCO2 altered biofilm development, allowing serpulids to do
      best at the acidified site by the end of the experiment, although early
      (pretransplant) negative effects of pCO2 on recruitment of these worms were still
      detectable. The ascidians Diplosoma sp. and Botryllus sp. settled later and were
      more tolerant to acidification. Overall, transient and persistent acidification
      driven changes in the biofouling community, via both past and more recent
      exposure, could have important implications for ecosystem function and food web
      dynamics.

PMID- 28762602
TI  - Hematopoietic stem cell transplantation in pediatric patients with acute myeloid
      leukemia without favorable cytogenetics.
AB  - Intensified chemotherapy, HSCT, and supportive care improve the survival of
      pediatric patients with AML. However, no consensus has been reached regarding the
      role of HSCT in patients without favorable cytogenetics. We evaluated OS and EFS
      according to prognostic factors that affect clinical outcomes, including
      cytogenetics risk group, conditioning regimen, donor type, disease status at the
      time of HSCT, and number of chemotherapy cycles prior to HSCT in 65 pediatric
      patients with AML without favorable cytogenetics who underwent HSCT. Fifteen of
      the 65 patients died: three of TRM and 12 of disease-related mortality. The 5
      year OS and EFS were 78.0% and 72.0%, respectively, and the 5-year cumulative
      relapse and TRM rates were 26.9% and 5.1%, respectively. Survival rates were not
      influenced by cytogenetic group (intermediated vs. poor), donor type (related vs.
      unrelated), transplant type (myeloablative vs. reduced-intensity conditioning),
      or number of pretransplant chemotherapy cycles (<=3 vs. >3 cycles). The low TRM
      rate and encouraging outcomes suggest that HSCT may be a feasible treatment for
      pediatric patients with AML without favorable cytogenetics.

PMID- 28762603
TI  - Combining informal care and paid work: The use of work arrangements by working
      adult-child caregivers in the Netherlands.
AB  - An increasing number of people combine paid work with the provision of informal
      care for a loved one. This combination of work and care may cause difficulties,
      necessitating adaptations at work, i.e. work arrangements. The present study
      explores what types of work arrangements are used by working caregivers, and
      which caregiver, care and work characteristics are associated with the use of
      these work arrangements. Within the Lifelines Informal Care Add-on Study
      (Lifelines ICAS), data on 965 Dutch informal caregivers in the North of the
      Netherlands were collected between May 2013 and July 2014 (response rate 48%),
      and data on 333 working adult-child caregivers (aged 26-68 years, 82% female)
      were used in this study. A small majority (56%) of the working caregivers used
      one or more work arrangement(s): taking time off (41%), individual agreements
      with supervisor (30%), formal care leave arrangement (13%), and reduction in paid
      work hours (6%). Logistic regression analyses showed that long working hours (OR
      1.06, 95% CI 1.01-1.08), and the experience of more health problems (OR 2.54, 95%
      CI 1.56-4.05) or a disrupted schedule due to caregiving (OR 2.50, 95% CI 1.66
      3.78) increased the chance to have used one or more work arrangements. Lower
      educated working caregivers were less likely to have used a formal care leave
      arrangement (tertiary vs. primary education OR 2.75, 95% CI 1.13-6.67; tertiary
      vs. secondary education OR 1.27, 95% CI 1.27-5.09). Policy makers should inform
      working caregivers about the availability of the different work arrangements,
      with specific attention for low educated working caregivers. Employers need to
      consider a more caregiver-friendly policy, as almost half of the working adult
      child caregivers did not use any work arrangement.

PMID- 28762605
TI  - Ensemblator v3: Robust atom-level comparative analyses and classification of
      protein structure ensembles.
AB  - Ensembles of protein structures are increasingly used to represent the
      conformational variation of a protein as determined by experiment and/or by
      molecular simulations, as well as uncertainties that may be associated with
      structure determinations or predictions. Making the best use of such information
      requires the ability to quantitatively compare entire ensembles. For this reason,
      we recently introduced the Ensemblator (Clark et al., Protein Sci 2015; 24:1528),
      a novel approach to compare user-defined groups of models, in residue level
      detail. Here we describe Ensemblator v3, an open-source program that employs the
      same basic ensemble comparison strategy but includes major advances that make it
      more robust, powerful, and user-friendly. Ensemblator v3 carries out multiple
      sequence alignments to facilitate the generation of ensembles from non-identical
      input structures, automatically optimizes the key global overlay parameter,
      optionally performs "ensemble clustering" to classify the models into subgroups,
      and calculates a novel "discrimination index" that quantifies similarities and
      differences, at residue or atom level, between each pair of subgroups. The
      clustering and automatic options mean that no pre-knowledge about an ensemble is
      required for its analysis. After describing the novel features of Ensemblator v3,
      we demonstrate its utility using three case studies that illustrate the ease with
      which complex analyses are accomplished, and the kinds of insights derived from
      clustering into subgroups and from the detailed information that locates
      significant differences. The Ensemblator v3 enhances the structural biology
      toolbox by greatly expanding the kinds of problems to which this ensemble
      comparison strategy can be applied.

PMID- 28762604
TI  - TMEFF2 shedding is regulated by oxidative stress and mediated by ADAMs and
      transmembrane serine proteases implicated in prostate cancer.
AB  - TMEFF2 is a type I transmembrane protein with two follistatin (FS) and one EGF
      like domain over-expressed in prostate cancer; however its biological role in
      prostate cancer development and progression remains unclear, which may, at least
      in part, be explained by its proteolytic processing. The extracellular part of
      TMEFF2 (TMEFF2-ECD) is cleaved by ADAM17 and the membrane-retained fragment is
      further processed by the gamma-secretase complex. TMEFF2 shedding is increased
      with cell crowding, a condition associated with the tumour microenvironment,
      which was mediated by oxidative stress signalling, requiring jun-kinase (JNK)
      activation. Moreover, we have identified that TMEFF2 is also a novel substrate
      for other proteases implicated in prostate cancer, including two ADAMs (ADAM9 and
      ADAM12) and the type II transmembrane serine proteinases (TTSPs) matriptase-1 and
      hepsin. Whereas cleavage by ADAM9 and ADAM12 generates previously identified
      TMEFF2-ECD, proteolytic processing by matriptase-1 and hepsin produced TMEFF2
      fragments, composed of TMEFF2-ECD or FS and/or EGF-like domains as well as novel
      membrane retained fragments. Differential TMEFF2 processing from a single
      transmembrane protein may be a general mechanism to modulate transmembrane
      protein levels and domains, dependent on the repertoire of ADAMs or TTSPs
      expressed by the target cell.

PMID- 28762606
TI  - D-dimer to guide the intensity of anticoagulation in Chinese patients after
      mechanical heart valve replacement: a randomized controlled trial.
AB  - : Essentials Low anticoagulation intensity reduces bleeding but increases
      thrombosis during warfarin therapy. Elevated D-dimer level is associated with
      increased thrombosis events. D-dimer can be used to find potential thrombosis in
      those receiving low intensity therapy. D-dimer-guided therapy may be the optimal
      strategy for those with mechanical heart valve replacement. SUMMARY: Background
      Controversies remain regarding the optimal anticoagulation intensity for Chinese
      patients after mechanical heart valve replacement despite guidelines having
      recommended a standard anticoagulation intensity. Objectives To investigate
      whether D-dimer could be used to determine the optimal anticoagulation intensity
      in Chinese patients after mechanical heart valve replacement. Patients/Methods
      This was a prospective, randomized controlled clinical study. A total of 748
      patients following mechanical heart valve replacement in Wuhan Asia Heart
      Hospital were randomized to three groups at a ratio of 1 : 1 : 1. Patients in two
      control groups received warfarin therapy based on constant standard intensity
      (international normalized ratio [INR], 2.5-3.5; n = 250) and low intensity (INR,
      1.8-2.6; n = 248), respectively. In the experimental group (n = 250), warfarin
      therapy was initiated at low intensity, then those with elevated D-dimer levels
      were adjusted to standard intensity. All patients were followed-up for 24 months
      until the occurrence of endpoints, including bleeding events, thrombotic events
      and all-cause mortality. Results A total of 718 patients were included in the
      analysis. Fifty-three events occurred during follow-up. There was less hemorrhage
      (3/240 vs. 16/241; hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.07
      0.45) and all-cause mortality (4/240 vs. 12/241; HR, 0.33; 95% CI, 0.12-0.87)
      observed in the D-dimer-guided group than in the standard-intensity group. A
      lower incidence of thrombotic events was also observed in the D-dimer-guided
      group when compared with the low-intensity group (5/240 vs. 14/237; HR, 0.35; 95%
      CI, 0.14-0.85). Overall, the total events were less in the D-dimer-guided group
      (9/240) when compared with the other two control groups (24/241, 20/237; HR,
      0.37, 0.44; 95% CI, 0.19-0.72, 0.21-0.90 Conclusions The D-dimer-guided
      adjustment of anticoagulation intensity could reduce adverse events in Chinese
      patients after mechanical heart valve replacement. TRIAL REGISTRY: NCT01996657;
      ClinicalTrials.gov.

PMID- 28762608
TI  - Truncating mutation in CSNK2B and myoclonic epilepsy.

PMID- 28762609
TI  - Postural change in convulsive seizures: a retrospective review of video
      electroencephalographic recordings.
AB  - BACKGROUND: Prone position has been identified as an important risk factor for
      sudden unexpected death in epilepsy raising the possibility of avoidance of this
      posture in sleep as a preventative measure. AIMS: To evaluate the potential
      utility of prone posture position, we studied patterns of postural change during
      generalised tonic clonic seizures. METHODS: Video-electroencephalographic
      recordings of patients undergoing investigations at the Royal Brisbane and
      Women's Hospital between 2005 and 2013 were reviewed independently by two raters.
      Head and truncal positions (left and right lateral, supine, sitting, prone) at
      seizure onset and offset, before and after nurse interventions were recorded.
      Post-ictal postural changes and evidence of stertorous respirations were also
      recorded. RESULTS: Thirty-one seizures from 27 patients were included in the
      study. One seizure began with the patient asleep in the prone position. One
      patient became prone during a seizure, having previously been asleep in the left
      lateral position. Nine patients changed position during a seizure. Seven of these
      patients were sitting or in a lateral position at the time of seizure onset, two
      patients were supine at seizure onset. No patient rolled by more than 90 degrees 
      during a seizure. Post-ictal stertorous respirations were observed in 14
      patients, one of whom was prone. CONCLUSION: The incidence of patients attaining
      a prone position during a seizure was low. Given that no patient rolled more than
      90 degrees , patients are least likely to attain a prone position if they are
      supine at the beginning of a seizure.

PMID- 28762610
TI  - Petrichor.

PMID- 28762607
TI  - Measures of fidelity of delivery of, and engagement with, complex, face-to-face
      health behaviour change interventions: A systematic review of measure quality.
AB  - PURPOSE: Understanding the effectiveness of complex, face-to-face health
      behaviour change interventions requires high-quality measures to assess fidelity
      of delivery and engagement. This systematic review aimed to (1) identify the
      types of measures used to monitor fidelity of delivery of, and engagement with,
      complex, face-to-face health behaviour change interventions and (2) describe the
      reporting of psychometric and implementation qualities. METHODS: Electronic
      databases were searched, systematic reviews and reference lists were hand
      searched, and 21 experts were contacted to identify articles. Studies that
      quantitatively measured fidelity of delivery of, and/or engagement with, a
      complex, face-to-face health behaviour change intervention for adults were
      included. Data on interventions, measures, and psychometric and implementation
      qualities were extracted and synthesized using narrative analysis. RESULTS: Sixty
      six studies were included: 24 measured both fidelity of delivery and engagement,
      20 measured fidelity of delivery, and 22 measured engagement. Measures of
      fidelity of delivery included observation (n = 17; 38.6%), self-report (n = 15;
      34%), quantitatively rated qualitative interviews (n = 1; 2.3%), or multiple
      measures (n = 11; 25%). Measures of engagement included self-report (n = 18;
      39.1%), intervention records (n = 11; 24%), or multiple measures (n = 17; 37%).
      Fifty-one studies (77%) reported at least one psychometric or implementation
      quality; 49 studies (74.2%) reported at least one psychometric quality, and 17
      studies (25.8%) reported at least one implementation quality. CONCLUSION: Fewer
      than half of the reviewed studies measured both fidelity of delivery of, and
      engagement with complex, face-to-face health behaviour change interventions. More
      studies reported psychometric qualities than implementation qualities.
      Interpretation of intervention outcomes from fidelity of delivery and engagement
      measurements may be limited due to a lack of reporting of psychometric and
      implementation qualities. Statement of contribution What is already known on this
      subject? Evidence of fidelity and engagement is needed to understand
      effectiveness of complex interventions Evidence of fidelity and engagement are
      rarely reported High-quality measures are needed to measure fidelity and
      engagement What does this study add? Evidence that indicators of quality of
      measures are reported in some studies Evidence that psychometric qualities are
      reported more frequently than implementation qualities A recommendation for
      intervention evaluations to report indicators of quality of fidelity and
      engagement measures.

PMID- 28762611
TI  - Pregnancy on short-daily home hemodialysis using low dialysate flow rate: A new
      hope for the end-stage renal disease patients.
AB  - INTRODUCTION: In France in 2014, there were approximately 1500 patients of
      reproductive age treated by dialysis. Pregnancy in these patients remains rare,
      however, the incidence has increased since the 2000s, with a parallel increase in
      the fetal survival rate. We report 2 cases of pregnancy in short-daily home
      hemodialysis using low dialysate flow rate. METHODS: Short-daily hemodialysis was
      continued at the request of the patients. The treatment consisted in an increase
      of frequency and duration of hemodialysis sessions, an independent blood pressure
      and dry weight control supervised by nephrological monitoring twice a month and a
      regular obstetrics follow-up. FINDINGS: Both patients continued hemodialysis at
      home until delivery and gave birth to 2 moderately premature babies, without
      other complication and resumed short-daily home hemodialysis fastly after
      delivery. CONCLUSION: Short-daily hemodialysis using low dialysate flow rate
      during pregnancy seems to allow a good control of uremia and blood pressure
      without requiring a major increase of weekly dialysis duration. Therefore, it
      could become an alternative to other hemodialysis programs while allowing the
      patients to continue their treatment at home. However, other studies are
      necessary in order to define the position of this procedure during pregnancy.

PMID- 28762612
TI  - Dissecting seed dormancy and germination in Aquilegia barbaricina, through
      thermal kinetics of embryo growth.
AB  - Threshold-based thermal time models provide insight into the physiological switch
      from the dormant to the non-dormant germinating seed. This approach was used to
      quantify the different growth responses of the embryo of seeds purported to have
      morphophysiological dormancy (MPD) through the complex phases of dormancy release
      and germination. Aquilegia barbaricina seeds were incubated at constant
      temperatures (10-25  degrees C) and 25/10  degrees C, without pre-treatment,
      after warm+cold stratification (W+C) and GA3 treatment. Embryo growth was
      assessed and the time of testa and endosperm rupture scored. Base temperatures
      (Tb ) and thermal times for 50% (theta50 ) of embryo growth and seed germination
      were calculated. W+C enabled slow embryo growth. W+C and GA3 promoted rapid
      embryo growth and subsequent radicle emergence. The embryo internal growth base
      temperature (Tbe ) was ca. 5  degrees C for W+C and GA3 -treated seeds. GA3
      treatment also resulted in similar Tb estimates for radicle emergence. The
      thermal times for embryo growth (thetae50 ) and germination (thetag50 ) were four
      to six-fold longer in the presence of GA3 compared to W+C. A. barbaricina is
      characterised by a multi-step seed germination. The slow embryo growth during W+C
      reflects continuation of the maternal programme of development, whilst the
      thermal kinetics of both embryo and radicle growth after the removal of
      physiological dormancy are distinctly different. The effects of W+C on the
      multiphasic germination response in MPD seeds are only partially mimicked by 250
      mg.l-1 GA3 . The thermal time approach could be a valid tool to model thermal
      kinetics of embryo growth and radicle protrusion.

PMID- 28762613
TI  - Visual Attention to Ambiguous Emotional Faces in Eating Disorders: Role of
      Alexithymia.
AB  - Eating disorders (EDs) are often accompanied by social-emotional problems.
      Recently, alexithymia has been suggested to explain objective emotion processing
      deficits in EDs. We tested if elevated levels of alexithymia may explain
      emotional face-processing problems in a mixed ED group (N = 24, 19 with anorexia
      and five with bulimia), comparing them with high-alexithymic (N = 25) and low
      alexithymic healthy controls (N = 25). Participants judged the mixture ratio of
      clear and ambiguous facial emotion blends while eye movements were recorded. The
      ED group was less accurate judging ambiguous blends containing anger or disgust
      and attended less to the faces compared with low-alexithymic controls. Reduced
      attention to faces, in particular the eye region, was linked to confusion with
      ambiguous anger and disgust in the ED group only. Although significant group
      differences only emerged compared with low-alexithymic controls, the visual
      attention patterns underlying the ED group's problems with subtle anger and
      disgust expressions were not driven by alexithymia. Copyright (c) 2017 John Wiley
      & Sons, Ltd and Eating Disorders Association.

PMID- 28762614
TI  - Distance to screening site and older adults' participation in cognitive
      impairment screening.
AB  - AIM: To develop intervention strategies that promote screening for cognitive
      impairment, it is essential to identify the modifiable predictors for
      participation in screening. The present study aimed to examine whether a shorter
      distance to the screening site predicted participation in screening for cognitive
      impairment, and whether interactive effects of the distance and psychological
      factors on the participation would be observed among community-dwelling older
      adults. METHODS: The study used a prospective design. After a baseline
      questionnaire survey, participation in screening for cognitive impairment was
      followed for 6 months (n = 9616). The distance to the screening site was measured
      by road distance from each residential address and categorized into four groups
      (<1 km, 1-1.99 km, 2-2.99 km, >=3 km). The questionnaire measured psychological
      factors (behavioral intention and perceived benefits of screening), driving
      status and demographic factors. RESULTS: A logistic regression analysis showed
      that compared with the <1 km group, the 2-2.99 km (adjusted odds ratio 0.62, P =
      0.040) and >=3 km (adjusted odds ratio 0.54, P = 0.015) groups did not
      participate in screening after adjusting for psychological and demographic
      factors, and driving status. The interaction of the distances and psychological
      factors on participation were not significant. CONCLUSIONS: The distance to the
      screening site predicted participation in cognitive impairment screening among
      older adults regardless of their psychological status. This finding shows that
      improving access to screening sites would be effective for promoting screening
      for cognitive impairments among both low and highly motivated older adults.
      Geriatr Gerontol Int 2018; 18: 146-153.

PMID- 28762615
TI  - Plasma cell neoplasm as a risk factor for early thrombosis of arteriovenous
      fistula.
AB  - INTRODUCTION: We hypothesized that presence of plasma cell neoplasms might be a
      risk for thrombosis of arteriovenous fistulas (AVFs) as well as other well-known
      factors including age, sex, race, and presence of diabetes mellitus or certain
      vascular disorders. METHODS: In this single-center, retrospective study based on
      medical record data, we investigated the influence of plasma cell neoplasms and
      the above-mentioned factors on the occurrence of complete occlusive thrombosis of
      the AVF within 30 days after surgery for creation of the AVF. Thrombosis was
      defined as the absence of bruit or thrill on auscultation and palpation,
      throughout systole and diastole. FINDINGS: We retrospectively assessed the
      medical records of 91 patients with end-stage renal failure, including 8 patients
      with plasma cell neoplasm (5 with multiple myeloma and 3 with amyloid light-chain
      amyloidosis), who underwent surgical creation of an AVF at the wrist or
      anatomical snuff box for the first time between April 2014 and December 2016.
      Early thrombosis (i.e., within 30 days of surgery) occurred in 50.0% (4/8) and
      10.8% (9/83) of patients with and without plasma cell neoplasm, respectively (P =
      0.013). Multivariate analysis revealed that, after adjusting for baseline
      characteristics, plasma cell neoplasm was the only significant risk factor for
      early AVF thrombosis (odds ratio, 38.8; 95% confidence interval, 4.0-378.9; P =
      0.0017). DISCUSSION: Considering the poor prognosis of plasma cell neoplasm and
      its association with higher risk for AVF thrombosis, another type of vascular
      access is likely to be more suitable than AVF in such patients.

PMID- 28762616
TI  - Policy choices in dementia care-An exploratory analysis of the Alberta continuing
      care system (ACCS) using system dynamics.
AB  - BACKGROUND: The increase in the incidence of dementia in the aging population and
      the decrease in the availability of informal caregivers put pressure on
      continuing care systems to care for a growing number of people with disabilities.
      Policy changes in the continuing care system need to address this shift in the
      population structure. One of the most effective tools for assessing policies in
      complex systems is system dynamics. Nevertheless, this method is underused in
      continuing care capacity planning. METHODS: A system dynamics model of the
      Alberta Continuing Care System was developed using stylized data. Sensitivity
      analyses and policy evaluations were conducted to demonstrate the use of system
      dynamics modelling in this area of public health planning. We focused our policy
      exploration on introducing staff/resident benchmarks in both supportive living
      and long-term care (LTC). RESULTS: The sensitivity analyses presented in this
      paper help identify leverage points in the system that need to be acknowledged
      when policy decisions are made. Our policy explorations showed that the deficits
      of staff increase dramatically when benchmarks are introduced, as expected, but
      at the end of the simulation period, the difference in deficits of both nurses
      and health care aids are similar between the 2 scenarios tested. Modifying the
      benchmarks in LTC only versus in both supportive living and LTC has similar
      effects on staff deficits in long term, under the assumptions of this particular
      model. CONCLUSION: The continuing care system dynamics model can be used to test
      various policy scenarios, allowing decision makers to visualize the effect of a
      certain policy choice on different system variables and to compare different
      policy options. Our exploration illustrates the use of system dynamics models for
      policy making in complex health care systems.

PMID- 28762617
TI  - Effect of extended-duration thromboprophylaxis on venous thromboembolism and
      major bleeding among acutely ill hospitalized medical patients: a bivariate
      analysis.
AB  - : Essentials Anticoagulants prevent venous thromboembolism but may be associated
      with greater bleeding risks. Bivariate analysis assumes a non-linear relationship
      between efficacy and safety outcomes. Extended full-dose betrixaban is favorable
      over standard enoxaparin in bivariate endpoint. Clinicians must weigh efficacy
      and safety outcomes in decision-making on thromboprophylaxis. SUMMARY: Background
      Among acutely ill hospitalized medical patients, extended-duration
      thromboprophylaxis reduces the risk of venous thromboembolism (VTE), but some
      pharmacologic strategies have been associated with greater risks of major
      bleeding, thereby offsetting the net clinical benefit (NCB). Methods To assess
      the risk-benefit profile of anticoagulation regimens, a previously described
      bivariate method that does not assume a linear risk-benefit tradeoff and can
      accommodate different margins for efficacy and safety was performed to
      simultaneously assess efficacy (symptomatic VTE) and safety (major bleeding) on
      the basis of data from four randomized controlled trials of extended-duration (30
      46 days) versus standard-duration (6-14 days) thromboprophylaxis among 28 227
      patients (EXCLAIM, ADOPT, MAGELLAN and APEX trials). Results Extended
      thromboprophylaxis with full-dose betrixaban (80 mg once daily) was superior in
      efficacy and non-inferior in safety to standard-duration enoxaparin, and showed a
      significantly favorable NCB, with a risk difference of - 0.51% (- 0.89% to -
      0.10%) in the bivariate outcome. Extended enoxaparin was superior in efficacy and
      inferior in safety (bivariate outcome: 0.03% [- 0.37% to 0.43%]), whereas
      apixaban and rivaroxaban were non-inferior in efficacy and inferior in safety (-
      0.20% [- 0.49% to 0.17%] and 0.23% [- 0.16% to 0.69%], respectively). Reduced
      dose betrixaban did not show a significant difference in either efficacy or
      safety (0.41% [- 0.85% to 1.94%]). Conclusions In a bivariate analysis that
      assumes non-linear risk-benefit tradeoffs, extended prophylaxis with full-dose
      betrixaban was superior to standard-duration enoxaparin, whereas other regimens
      failed to simultaneously achieve both superiority and non-inferiority with
      respect to symptomatic VTE and major bleeding in the management of acutely ill
      hospitalized medical patients.

PMID- 28762618
TI  - Exploring disparities in receipt of adjuvant chemotherapy in culturally and
      linguistically diverse groups: an Australian centre's experience.
AB  - BACKGROUND: Globally, racial and ethnic disparities exist in treatments and
      outcomes for cancer patients. In Australia, there are few published data related
      to cancer patients from culturally and linguistically diverse (CALD) backgrounds.
      AIM: To explore disparities in adjuvant chemotherapy utilisation in cancer
      patients from CALD groups. METHODS: Retrospective analysis of patients who were
      recommended adjuvant chemotherapy for early stage breast cancer or early stage
      colorectal cancer between July 2011 and October 2014 was performed. Rates of
      adjuvant chemotherapy uptake were analysed between those who identified English
      as their first-preferred language, versus those who did not, as well as between
      patients who were born in a country where English is the main language (non
      CALD), versus those born in a country where English is not the main language
      (CALD). RESULTS: Two hundred and eleven patients were identified. One hundred and
      forty-three (67.7%) patients had early stage breast cancer and 68 (32.2%)
      patients had early stage colorectal cancer. No difference was detected in the
      acceptance of adjuvant chemotherapy between non-CALD (80.9%) and CALD patients
      (81.3%, P = 0.984) or between patients who identified English as their first
      preferred language (80.8%) and those who did not (81.8%, P = 0.870). There was no
      difference in the rate of chemotherapy completion, with 75.6% completion in the
      non-English-speaking group and 81.1% in the English-speaking group (P = 0.426).
      CONCLUSION: No difference was observed in adjuvant chemotherapy utilisation in
      patients who identified English as their first-preferred language compared to
      those who did not, as well as between non-CALD and CALD groups. This is the first
      study to assess these differences in Australia.

PMID- 28762620
TI  - A case of Chediak-Higashi syndrome presented with accelerated phase could be
      treated effectively by unrelated cord blood transplantation.
AB  - CHS is a rare immunodeficiency syndrome with defects in the functions of
      cytotoxic cells and neutrophils. Approximately 85% of patients with CHS undergo
      an AP within the first decade, which is similar to FHLH. Chemotherapy could
      induce transient remission, but only allogeneic HCT could correct the underlying
      genetic defect and prevent relapse. We reported a case of CHS diagnosed at 19
      months, who had an elder brother who had previously succumbed to the same
      disease. The little girl presented with severe AP manifestations including
      recurrent high fever, enlarged superficial lymph nodes, and extraordinary
      hepatosplenomegaly occupying the whole abdominal and pelvic cavity. Comprehensive
      therapies including HLH 2004 protocol, supportive care, and antibiotics,
      especially antituberculous agents, were given to her to induce remission. After
      remission, the patient received fully HLA-matched UCBT. The transplantation
      course was uneventful, except for fluctuation of donor chimerism. The patient has
      been alive for 36 months without infection and neurologic manifestations and is
      under further follow-up. Our result provides another case that UCBT can be
      effective for treating patients with CHS and remission before HCT is important
      for good prognosis.

PMID- 28762619
TI  - Crowd sourcing difficult problems in protein science.
AB  - Dedicated computing resources are expensive to develop, maintain, and
      administrate. Frequently, research groups require bursts of computing power,
      during which progress is still limited by available computing resources. One way
      to alleviate this bottleneck would be to use additional computing resources.
      Today, many computing devices remain idle most of the time. Passive volunteer
      computing exploits this unemployed reserve of computing power by allowing device
      owners to donate computing time on their own devices. Another complementary way
      to alleviate bottlenecks in computing resources is to use more efficient
      algorithms. Engaging volunteer computing employs human intuition to help solve
      challenging problems for which efficient algorithms are difficult to develop or
      unavailable. Designing engaging volunteer computing projects is challenging but
      can result in high-quality solutions. Here, we highlight four examples.

PMID- 28762621
TI  - Repair of damaged ligaments with tissue fixation system minisling is sufficient
      to cure major prolapse in all three compartments: 5-year data.
AB  - AIM: The ageing population in Japan brings problems of pelvic organ prolapse
      (POP), bladder and bowel incontinence, and fragility as regards major pelvic
      surgery. Existing data from tissue fixation system (TFS) surgery show high cure
      rates for these conditions, but long-term data are lacking. We aimed to elucidate
      the usefulness of TFS by assessing 5-year postoperative outcomes. METHODS: A
      total of 68 patients, mean age 70 years, underwent total pelvic floor repair.
      Cystocele, apical prolapse, and rectocele were variously addressed by TFS repair
      of pubourethral, arcus tendineus fasciae pelvis, cardinal, uterosacral, and
      perineal body ligaments using a mean 3.2 tapes per patient (n = 216). Patients
      were followed up at 12 months then yearly. We included patients with third- or
      fourth-degree uterine/vaginal prolapse (POP Quantification classification). We
      excluded patients with serious comorbid conditions. RESULTS: The mean operating
      time was 88 min and the mean blood loss was 78 mL. There was minimal
      postoperative pain and urinary retention, as evidenced by a mean hospital stay of
      0.8 days and early return to normal activities. The 5-year cure rates for urinary
      stress incontinence, urgency, nocturia, and frequency were 82%, 91.7%, 58%, and
      52%, respectively. The surgical cure rate for POP was 87.1% at 12 months, falling
      to 79.0 at 60 months. The cumulative 5-year erosion rate was 0% and 1.7% for all
      ligaments except the perineal body (25.7%), reducing to 2.6% by year 5 following
      anchor placement into deep transversus perinei. Two cases of ileus were
      attributed to incorrect technique. CONCLUSION: Reinforcing up to four ligaments
      with the TFS was sufficient for cure of third- and fourth-degree POP. The
      technique is minimally invasive, suitable for elderly women, and effective at 5
      years for both anatomical and symptom cure.

PMID- 28762622
TI  - Quantitative structure-activity relationship (QSAR) directed the discovery of 3
      (pyridin-2-yl)benzenesulfonamide derivatives as novel herbicidal agents.
AB  - BACKGROUND: Agrochemicals have been crucial to the production of food, and the
      need for the development of novel agrochemicals continues unceasing owing to the
      loss of existing produces via the growth of resistance and the desire for
      products with more propitious environmental and toxicological patterns. RESULTS:
      The results of both CoMFA and CoMSIA models indicated that biological activity
      can effectively be improved through the structural optimisation and molecular
      design of these synthetic compounds from the aspects of steric, electrostatic,
      hydrophobic, hydrogen bond donor and acceptor fields. Data of postemergence
      herbicidal activity in the greenhouse explained that most new 3-(pyridin-2
      yl)benzenesulfonamide derivatives (4c-4 t) could control highly effectively
      against barnyardgrass, foxtail, vetleaf, and youth and old age (herbicidal
      activity >=90%); for example, compounds 4q-4 t exhibit excellent biological
      activity equivalent/superior to commercial saflufenacil/sulcotrione at the low
      concentration of 37.5 g a.i./ha, and in particular, the herbicidal activity of
      compound 4 t for four experimental plant species is found to be notably greater
      than saflufenacil (3.75 g a.i./ha). Meanwhile, compound 4 t also has good crop
      selectivity for weed control in maize. CONCLUSION: The novel compounds such as 4
      t have remarkable biological activity after the structural optimisation utilising
      the constructed 3D-QSAR models, i.e. such QSAR models have great accuracy. (c)
      2017 Society of Chemical Industry.

PMID- 28762623
TI  - Clinical and economic evaluation of a Case Management Service for patients with
      back pain.
AB  - AIM: To evaluate the clinical-effectiveness and resource use associated with Case
      Management Services in a UK private sector DESIGN: An observational cohort study
      based on prospective data collection of patient reported outcome measures and
      data collection from an existing administrative health database. SETTING: A
      United Kingdom (UK) private healthcare provider PARTICIPANTS: Consecutive
      referrals into the Case Management Service over a three-month period.
      INTERVENTIONS: Participants were managed within the Case Management Service in
      accordance with usual pathways. MAIN OUTCOME MEASURES: Outcome measures included
      EQ-5D-5L and PSFS. Measurements were taken at baseline, and repeated at the point
      at which the client's case was closed. The CARE measure examined patient reported
      experience. Cost Consequence analysis was completed using existing data for the
      same period of time in two separate years: 2014, two years after CMS
      implementation, and 2011, prior Case Management Service development RESULTS:
      There was a statistically significant improvement in quality of life (EQ-5D-5L p
      < 0.0001; EQ-VAS p < 0.001) and functional ability (p < 0.001) following the
      Physiotherapy Case Management. The CARE measure showed high levels of patient
      satisfaction with 96% of clients rating their individual case manager as good to
      excellent. The cost consequences analysis showed a cost reduction in therapy
      resource utilisation by L252 842 (from L10 772 875 to L10 520 034). CONCLUSIONS:
      The Case Management Service showed the provision to be providing significant
      improvement in quality of life and functional outcomes within efficient use of
      resources, and service users are highly satisfied with their experience.

PMID- 28762624
TI  - Chronic complications of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a common disease (~700 per 100 000) that is
      associated with significant risk of recurrence, chronic complications, and
      substantial mortality, with reported death rates of up to 40% at 10 years. The
      development of novel anticoagulants has revolutionized the treatment of acute
      VTE, while strategies for prevention and treatment of chronic complications still
      seek for such a landmark change. Impaired thrombus resolution is the common
      denominator behind VTE complications, which are postthrombotic syndrome (PTS) and
      chronic thromboembolic pulmonary hypertension (CTEPH). PTS and CTEPH are
      associated with substantial morbidity and high healthcare expenses. While PTS
      occurs in up to 50% of patients after symptomatic deep vein thrombosis, only a
      small and poorly defined number of patients are diagnosed with CTEPH after
      pulmonary embolism. This review is a comprehensive summary of VTE-related chronic
      complications, their epidemiology, diagnosis, and treatment.

PMID- 28762625
TI  - Don't look back.

PMID- 28762626
TI  - Adjustment of target weight based on absolute blood volume reduces the frequency
      of intradialytic morbid events.
AB  - INTRODUCTION: Adequate volume management removing excess volume and at the same
      time avoiding intradialytic morbid events (IME) remains a core problem in current
      hemodialysis (HD) therapy. Recently, we developed a feasible method to determine
      absolute blood volume (Vs, in mL/kg) in patients on HD. The aim of this study was
      to investigate the suitability of Vs measurements for volume management. METHODS:
      Following a 4 week baseline phase to quantify the frequency of IME, volume status
      was determined in a single specified HD session during which Vs was measured
      using dialysate dilution, volume overload (Vo, L) was measured using bioimpedance
      spectroscopy, and the occurrence of IME was recorded. Target weight was then
      adjusted and the frequency of IME was recorded during 4 weeks of follow-up.
      FINDINGS: Forty-five patients participated in this study. Twenty-two (49%)
      patients experienced 66 IME in 12% of HD treatments during baseline. In 15 (33%)
      patients who experienced IME during volume assessment both Vs (60.7 +/- 4.0 vs.
      73.7 +/- 11.3 mL/kg, P < 0.001) and Vo (1.1 +/- 0.9 vs. 2.5 +/- 1.8 L, P < 0.01)
      were significantly lower than in stable patients, respectively. The sensitivity,
      specificity, and accuracy of the <=65 mL/kg Vs threshold to predict IME was 87%,
      100%, and 91%, respectively. Target weight was increased (+1.5 kg) or decreased (
      5 kg) in 32 patients. The frequency of IME fell to 0.9% of all HD sessions in the
      following 4 weeks (P < 0.001). DISCUSSION: Adjustment of target weight based on
      information of Vs, Vo, and IME appears as a feasible approach to reduce the
      frequency of IME.

PMID- 28762627
TI  - Clinician provision of oncofertility support in cancer patients of a reproductive
      age: A systematic review.
AB  - OBJECTIVE: The emerging discipline of oncofertility advocates for the timely
      provision of fertility information and referral for fertility preservation to all
      cancer patients of reproductive age (<45 years). A systematic review was
      undertaken on the clinician provision of oncofertility support to determine
      whether cancer patients are having their support needs adequately met by staff.
      METHODS: An initial search conducted in May 2016 identified 351 potentially
      relevant studies. The papers were divided into 2 categories: Papers on the
      clinician provision of oncofertility support were reviewed for this study, and
      papers on patient oncofertility support needs were reviewed for a separate
      systematic review. RESULTS: A total of 23 studies were included within the final
      review of this manuscript. Although many clinicians are broadly informed about
      the risk to their patients' fertility brought about by cancer treatment, there
      are many factors which hinder the appropriate discussion, referral, or service
      utilisation needed to provide adequate oncofertility support to patients of
      reproductive age. CONCLUSIONS: Oncofertility support is often not delivered to
      the standard of current guidelines, with many clinicians not providing the
      recommended care to all eligible patients, and as such many patients may lack the
      oncofertility support that they require. The implementation of a clear procedural
      process would assist clinicians in the provision of oncofertility support for
      cancer patients of reproductive age.

PMID- 28762628
TI  - Prognostic value of physical function tests and muscle mass in elderly
      hospitalized patients. A prospective observational study.
AB  - AIM: To determine the prognostic value for mortality of physical function tests,
      muscle mass loss, disability and frailty in elderly hospitalized patients.
      METHODS: We prospectively included 298 hospitalized patients aged >60 years (152
      men and 146 women). We assessed comorbidity using the Charlson Comorbidity Index;
      nutrition by body mass index, midarm muscle area and subjective nutritional
      score; physical muscle function by handgrip strength, gait speed, standing
      balance and stand up test; disability using the Barthel test and activities of
      daily living; frailty by the clinical frailty scale and Fried frailty index; and
      cognitive impairment by the Pfeiffer test. We assessed 100-day and long-term
      mortality. RESULTS: We found a high prevalence of malnutrition, comorbidity,
      cognitive impairment, physical function impairment, disability and frailty.
      Mortality at 100 days was 15.1%, with a long-term median survival of 989 days.
      Mortality was significantly related to age, comorbidity, nutritional status,
      physical function, disability and frailty. Serum vitamin D3 levels were not
      related to mortality. Independent prognostic value for long-term mortality was
      shown by: (i) incapacity to carry out any of the walking, stand up and standing
      balance tests; (ii) male sex; (iii) aged >80 years; (iv) impaired handgrip
      strength or gait speed; (v) Charlson Comorbidity Index >=1; and (6) impaired
      muscle mass of subjective nutritional score. CONCLUSIONS: In elderly hospitalized
      patients, there is an important role of muscle regarding prognosis, mainly
      related to physical function, but also and independently regarding muscle mass.
      Geriatr Gerontol Int 2018; 18: 57-64.

PMID- 28762629
TI  - Evaluation of blowfly larvae (Diptera: Calliphoridae) as possible reservoirs and
      mechanical vectors of African swine fever virus.
AB  - In 2014, highly virulent African swine fever virus (ASFV) was introduced into the
      Baltic States and Poland, with new cases being reported almost every week from
      wild boar and also from domestic pigs. Contrary to initial predictions that the
      disease would either die out due to the high virulence of the virus strain or
      spread rapidly in westerly direction, the infection became endemic and spread
      slowly. The unexpected disease epidemiology led to the hypothesis that hitherto
      unconsidered factors might contribute to virus persistence and dispersal. To
      check whether arthropod species feeding and developing on infected carcasses
      might be involved, larvae of two commonly found blowfly species, Lucilia sericata
      and Calliphora vicina, were experimentally bred on ASFV-infected spleen tissue.
      After different time intervals, developing larvae and pupae were tested for
      infectious virus and viral DNA. By qPCR, contamination of the blowfly larvae and
      pupae with ASFV-DNA could be demonstrated even after several washing steps,
      proving the uptake of virus during feeding in the larval stage. However,
      infectious virus could never be isolated. By contrast, the larvae appeared to
      have inactivated ASFV in the offered tissue, which might be explained by the
      known anti-biotic effect of salivary secretions. It is concluded that immature
      blowfly stages do not play a relevant role as reservoirs or mechanical vectors of
      ASFV.

PMID- 28762631
TI  - Prevalence and Risk Factors of Urinary Incontinence and Overactive Bladder in
      Japanese Women.
AB  - OBJECTIVES: The prevalence of storage symptoms, including stress urinary
      incontinence (SUI) and overactive bladder (OAB), is high in women worldwide. In
      Japan, there have been few large-scale epidemiological surveys of lower urinary
      tract symptoms (LUTS), and the risk factors for these symptoms are unclear. The
      aim of this study was to explore the prevalence and risk factors of storage
      symptoms in Japanese women. METHODS: A cross-sectional Internet survey was
      conducted in Japan. Five thousand women aged 20-79 years were selected to answer
      demographic questionnaires, Japanese version of International Consultation on
      Incontinence Questionnaire-Short Form, and the Overactive Bladder Symptom Score
      (OABSS) pertaining to their symptoms in the previous month. Descriptive
      statistics were used to evaluate the prevalence of storage symptoms. Logistic
      regression analysis was performed to determine risk factors for SUI and OAB.
      RESULTS: The answers from 4804 women (average age, 40.4 years) were analyzed. The
      prevalence of SUI was 16.7% (SUI, 13.0%; mixed urinary incontinence, 3.7%). The
      prevalence of OAB diagnosed on OABSS was 8.1%. The prevalence of SUI and OAB
      symptoms increased with age, and 68.0% of women had one or more storage symptoms.
      Age >=40 years, body mass index >=25 kg/m2 , and constipation were common risk
      factors for SUI and OAB. Childbirth was an additional risk factor for SUI.
      CONCLUSIONS: The prevalence of storage symptoms in Japanese women was high, and
      risk factors associated with these symptoms were similar to those reported in
      studies in other countries.

PMID- 28762630
TI  - Comparison of multiple electrode aggregometry with lumi-aggregometry for the
      diagnosis of patients with mild bleeding disorders.
AB  - : Essentials There is a clinical need for new technologies to measure platelet
      function in whole blood. Mild bleeding disorders were evaluated using multiple
      electrode aggregometry (MEA). MEA is insensitive at detecting patients with mild
      platelet function and secretion defects. More studies are required to investigate
      MEA in patients with a defined set of platelet disorders. SUMMARY: Background
      Multiple electrode aggregometry (MEA) measures changes in electrical impedance
      caused by platelet aggregation in whole blood. This approach is faster, more
      convenient and offers the advantage over light transmission aggregometry (LTA) of
      assessing platelet function in whole blood and reducing preanalytical errors
      associated with preparation of platelet-rich plasma (PRP). Several studies
      indicate the utility of this method in assessing platelet inhibition in
      individuals taking antiplatelet agents (e.g. aspirin and clopidogrel). Objective
      Our current study sought to evaluate the ability of MEA in diagnosing patients
      with mild bleeding disorders by comparison with light transmission lumi
      aggregometry (lumi-LTA). Methods Forty healthy subjects and 109 patients with a
      clinical diagnosis of a mild bleeding disorder were recruited into the UK
      Genotyping and Phenotyping of Platelets study (GAPP, ISRCTN 77951167). MEA was
      performed on whole blood using one or two concentrations of ADP, PAR-1 peptide,
      arachidonic acid and collagen. Lumi-LTA was performed in PRP using several
      concentrations of ADP, adrenaline, arachidonic acid, collagen, PAR-1 peptide and
      ristocetin. Results Of 109 patients tested, 54 (49%) patients gave abnormal
      responses by lumi-LTA to one or more agonists. In contrast, only 16 (15%)
      patients were shown to have abnormal responses to one or more agonists by MEA.
      Conclusions In this study we showed that MEA is less sensitive in identifying
      patients with abnormal platelet function relative to lumi-LTA.

PMID- 28762632
TI  - Complexity perspectives on clinical decision making in an intensive care unit.
AB  - RATIONALE, AIMS, AND OBJECTIVES: How to clarify the implications of complexity
      thinking for decision making in the intensive care unit (ICU)? METHOD:
      Retrospective qualitative empirical research. Practitioners in an ICU were
      interviewed on how their decisions were made regarding a particular patient in a
      difficult, clinical situation. Transcriptions of these interviews were coded and
      retrieved in Maxqda, a software program. Assisted by complexity thinking,
      researchers focused on the decision-making process and the shift from analytic
      approaches to complex approaches. RESULTS: Originally, practitioners took their
      decisions with negligible transdisciplinary interactivity, drawing on analytical
      knowledge. Later on, they shifted to transdisciplinary practices, paying
      attention to more participation in their decision-making processes within their
      complex environment. CONCLUSIONS: Complexity thinking demonstrates that this is a
      better model towards understanding transdisciplinary decision making then most
      analytical methodologies.

PMID- 28762633
TI  - Platelet activation and clotting cascade activation by dialyzers designed for
      high volume online hemodiafiltration.
AB  - INTRODUCTION: Hemodialysis patients are pro-thrombotic. Higher volume online
      postdilutional hemodiafiltration (OL-HDF), with increasing hematocrit increases
      the risk of clotting in the extracorporeal circuit (ECC). We wished to determine
      whether OL-HDF increased platelet activation and ECC clotting. METHODS:
      Coagulation parameters, platelet, white cell, and endothelial activation markers
      were measured at the start and end of dialysis sessions in 10 patients and also
      pre- and post-dialyzer after 15 minutes using two different dialyzers designed
      for high volume OL-HDF; cellulose triacetate (TAGP) and polysulphone (PS), and
      polyvinylpyrrolidone (PVP). Patients were anticoagulated with a heparin bolus.
      FINDINGS: At the start of OL-HDF, D dimers, thrombin antithrombin complexes
      (TATs), and soluble adhesions molecules (sICAM-1 and sVCAM-1) were increased.
      Post-treatment soluble P selectin (PS/PVP 26.7 +/- 7.1 versus 36.6 +/- 9.9; TAGP
      28.7 +/- 7.2 versus 43.5 +/- 8.4 ng/ml, P < 0.001), and soluble CD40 ligand
      (PS/PVP 297 +/- 228 versus 552 +/- 272, TAGP 245 +/- 187 versus 390 +/- 205
      ng/ml, P < 0.05) increased. Post-dialyzer concentrations increased versus pre
      dialyzer for tissue factor (PS/PVP 117 +/- 12 versus 136 +/- 16, TAGP 100 +/- 25
      versus 128 +/- 40 ng/ml, P < 0.05), factor VIIIc (PS/PVP 174 +/- 54 versus 237 +/
      83, TAGP 163 +/- 60 versus 247 +/- 102 IU/ml, P < 0.01), sVCAM-1 (PS/PVP 782 +/-
      64 versus 918 +/- 140, TAGP 722 +/- 121 versus 889 +/- 168 ng/ml, P < 0.01), and
      D-dimers (PS/PVP 292 +/- 132 versus 355 +/- 167, TAGP 300 +/- 129 versus 391 +/-
      171 ng/ml, P < 0.001). There was no macroscopic thrombus noted in the ECC, and no
      increase in microparticles, platelet factor-4, or TATs. DISCUSSION: Despite being
      pro-thrombotic, with activation of platelets, and lymphocytes during passage
      through ECC, no macroscopic clotting, or increased TATs were noted during OL-HDF,
      and no major differences between cellulosic and polysulphone dialyzers.

PMID- 28762634
TI  - Ultrathin Bi Nanosheets with Superior Photoluminescence.
AB  - Despite substantial progress in the science and technology of 2D nanomaterials,
      facile fabrication of ultrathin 2D metals remains challenging. Herein, an
      efficient hot-pressing method is developed to fabricate free-standing ultrathin
      Bi nanosheets from Bi nanoparticles. Highly crystalline Bi nanosheets with
      thickness as low as ~2 nm and area of more than several micrometers are
      successfully fabricated on silicon substrates. The ultrathin Bi nanosheets
      exhibit morphology and structural dependent enhanced broad range photoemission in
      visible region of spectrum. Our cost-effective hot-pressing strategy may open an
      insight for production, application, and deficient fundamental understanding of
      other 2D semimetals/metalloids and noble metals.

PMID- 28762635
TI  - A comparison of operative outcomes between standard and robotic laparoscopic
      surgery for endometrial cancer: A systematic review and meta-analysis.
AB  - BACKGROUND: Evidence has been systematically assessed comparing robotic with
      standard laparoscopy for treatment of endometrial cancer. METHODS: A search of
      Medline, Embase and Cochrane databases was performed until 30th October 2016.
      RESULTS: Thirty-six papers including 33 retrospective studies, two matched case
      control studies and one randomized controlled study were used in a meta-analysis.
      Information from a further seven registry/database studies were assessed
      descriptively. There were no differences in the duration of surgery but days stay
      in hospital were shorter in the robotic arm (0.46 days, 95%CI 0.26 to 0.66). A
      robotic approach had less blood loss (57.74 mL, 95%CI 38.29 to 77.20), less
      conversions to laparotomy (RR = 0.41, 95%CI 0.29 to 0.59), and less overall
      complications (RR = 0.82, 95%CI 0.72 to 0.93). A robotic approach had higher
      costs ($1746.20, 95%CI $63.37 to $3429.03). CONCLUSION: A robotic approach has
      favourable clinical outcomes but is more expensive.

PMID- 28762636
TI  - Blockage of Wnt/beta-Catenin Signaling by Nanoparticles Reduces Survival and
      Proliferation of CLL Cells In Vitro-Preliminary Study.
AB  - The Wnt/beta-catenin signaling pathway is shown to play a significant role in the
      control of the survival, proliferation, and differentiation of hematopoietic
      cells. Studies have confirmed that aberrant activation of canonical Wnt signaling
      occurs in various forms of leukemia, and is crucial for chronic lymphocytic
      leukemia (CLL) pathogenesis. The aim of the study is to evaluate the influence of
      maltotriose (M3) modified fourth generation poly(propylene imine) dendrimers (PPI
      G4) on Wnt/beta-catenin pathway gene expression in CLL (MEC-1) cells and to
      compare these findings with those obtained with fludarabine (FA). Microarray data
      analysis reveals seven of 19 Wnt/beta-catenin pathway genes whose expression
      changes significantly during dendrimer and FA treatment: WNT10A, WNT6, and CDH1
      among others. PPI-G4-M3 is already known to influence MEC-1 cell apoptosis and
      proliferation. The obtained results suggest that the reduction in cell survival
      under the influence of glycodendrimers and FA may be due to loss of Wnt
      signaling.

PMID- 28762638
TI  - Principles of treating enlarging pseudoaneurysm in a dialysis arteriovenous
      graft.
AB  - The arteriovenous graft (AVG) is one of the major types of permanent vascular
      access used to provide hemodialysis. Complications encountered with AVG use
      include stenosis, infection, thrombosis, and pseudoaneurysm formation. Venous
      outflow stenosis along with frequent needle cannulation at the same site can lead
      to breakdown of the graft material, resulting in pseudoaneurysm formation. In the
      following case, we illustrate common management principles used to treat
      pseudoaneurysms. While stent-grafts have been utilized for pseudoaneurysm repair,
      stent-graft usage is not always optimal. Surgical management may be an ideal
      choice of treatment. The role of educating the dialysis staff and patients is
      essential to identify and minimize the risk of pseudoaneurysm formation.

PMID- 28762637
TI  - Suppressing aflatoxin biosynthesis is not a breakthrough if not useful.
AB  - Liver-affecting, carcinogenic aflatoxins produced by Aspergillus spp. are a major
      problem, especially in the humid developing world where storage conditions are
      often optimal for the fungi. Peanuts and maize have been transformed with RNAi
      constructs targeting Aspergillus flavus polyketide-synthase, an early key enzyme
      in aflatoxin biosynthesis. Aflatoxin biosynthesis was suppressed in developing
      immature grain, less so in late maturing grain, and it is doubtful that the
      technology will be effective in near dry mature grain. The infected grain was
      still mouldy. As Aspergillus that infects grain preharvest can continue to grow
      and produce aflatoxin in poorly stored grain, and grain storage insects vector
      further infections, this technology seems to have little potential utility in the
      humid tropics. The biotechnological approaches of RNAi directly targeting
      Aspergillus, coupled with transgenic insecticidal proteins should be far more
      effective. These biotechnological approaches can be used in tandem with the RNAi
      against polyketide-synthase, as well as with irradiation, biocontrol and better
      grain drying and hermetic dry storage in a controlled atmosphere. (c) 2017
      Society of Chemical Industry.

PMID- 28762639
TI  - Zinc Imidazolate Metal-Organic Frameworks (ZIF-8) for Electrochemical Reduction
      of CO2 to CO.
AB  - Metal-organic frameworks (MOFs) are regarded as promising materials for CO2
      adsorption, which is an important step in CO2 electrochemical reduction. In this
      work, zeolitic imidazolate framework (ZIF-8) nanomaterials were synthesized with
      various zinc sources and used as electrocatalysts for CO2 reduction to CO. Among
      them, ZIF-8, prepared using ZnSO4 , delivers the best catalytic activity towards
      CO2 electroreduction, with 65 % CO yield. The main catalytic center can be
      attributed to the discrete Zn nodes in ZIF-8. Electrolytes are important in
      increasing the CO selectivity, and NaCl is the best suitable electrolyte due to
      facile anion exchange.

PMID- 28762641
TI  - MRI measurements of the thoracic aorta and pulmonary artery.
AB  - INTRODUCTION: The purpose of this study was to obtain a range of normal
      measurements of the adult thoracic aorta and main pulmonary artery using cardiac
      MRI, and to assess agreement between measurements made on ECG-gated two
      dimensional (2D) breath held steady-state-free precession (SSFP), and three
      dimensional (3D) breath held SSFP image acquisitions. METHODS: Forty-nine normal
      volunteers underwent cardiac MRI using a 1.5T system. Two independent examiners
      measured the ascending aorta, aortic arch, descending thoracic aorta and main
      pulmonary artery in pre-defined locations. RESULTS: Overall, inter-observer
      agreement for all measurements was excellent. Close agreement was observed in
      aortic diameters obtained from the 2D and 3D SSFP methods in six of the nine
      aortic measurement sites. There was a tendency for the 3D measurements to be
      smaller than the 2D measurements but this was only significant at two sites, the
      aortic annulus, and the ascending aorta. There was a significance difference in
      aortic measurements between the left carotid artery (LC) and the left subclavian
      artery (LSC). CONCLUSION: Normal values for transverse diameters of the thoracic
      aorta and main pulmonary artery were established using 2D and 3D non-contrast MR
      sequences in healthy adults. Overall both inter-observer agreement, and agreement
      between 2D and 3D techniques was good. Mean diameter differences demonstrated at
      the aortic annulus, ascending aorta and aortic arch between LC and LSC although
      significant were less than one millimetre and unlikely to be important in
      clinical practice.

PMID- 28762640
TI  - Exploring Bacterial Carboxylate Reductases for the Reduction of Bifunctional
      Carboxylic Acids.
AB  - Carboxylic acid reductases (CARs) selectively reduce carboxylic acids to
      aldehydes using ATP and NADPH as cofactors under mild conditions. Although CARs
      attracts significant interest, only a few enzymes have been characterized to
      date, whereas the vast majority of CARs have yet to be examined. Herein the
      authors report that 12 bacterial CARs reduces a broad range of bifunctional
      carboxylic acids containing oxo-, hydroxy-, amino-, or second carboxyl groups
      with several enzymes showing activity toward 4-hydroxybutanoic (4-HB) and adipic
      acids. These CARs exhibits significant reductase activity against substrates
      whose second functional group is separated from the carboxylate by at least three
      carbons with both carboxylate groups being reduced in dicarboxylic acids.
      Purified CARs supplemented with cofactor regenerating systems (for ATP and
      NADPH), an inorganic pyrophosphatase, and an aldo-keto reductase catalyzes a high
      conversion (50-76%) of 4-HB to 1,4-butanediol (1,4-BDO) and adipic acid to 1,6
      hexanediol (1,6-HDO). Likewise, Escherichia coli strains expressing eight
      different CARs efficiently reduces 4-HB to 1,4-BDO with 50-95% conversion,
      whereas adipic acid is reduced to a mixture of 6-hydroxyhexanoic acid (6-HHA) and
      1,6-HDO. Thus, our results illustrate the broad biochemical diversity of
      bacterial CARs and their compatibility with other enzymes for applications in
      biocatalysis.

PMID- 28762642
TI  - Genomic, Transcriptional, and Phenotypic Analysis of the Glucose Derepressed
      Clostridium beijerinckii Mutant Exhibiting Acid Crash Phenotype.
AB  - Clostridium beijerinckii is a predominant solventogenic bacterium that is used
      for the ABE fermentation. Various C. beijerinckii mutants are constructed for
      desirable phenotypes. The C. beijerinckii mutant BA105 harboring a glucose
      derepression phenotype was previously isolated and demonstrated the enhanced
      amylolytic activity in the presence of glucose. Despite its potential use, BA105
      is not further characterized and utilized. Therefore, the authors investigate
      fermentation phenotypes of BA105 in this study. Under the typical batch
      fermentation conditions, BA105 consistently exhibits acid crash phenotype
      resulting in limited glucose uptake and cell growth. However, when the culture pH
      is maintained above 5.5, BA105 exhibits the increased glucose uptake and butanol
      production than did the wild-type. To further analyze BA105, the authors perform
      genome sequencing and RNA sequencing. Genome analysis identifies two SNPs unique
      to BA105, in the upstream region of AbrB regulator (Cbei_4885) and the ROK family
      glucokinase (Cbei_4895) which are involved in catabolite repression and
      regulation of sugar metabolism. Transcriptional analysis of BA105 reveals
      significant differential expression of the genes associated with the PTS sugar
      transport system and acid production. This study improves understanding of the
      acid crash phenomenon and provides the genetic basis underlying the catabolite
      derepression phenotype of C. beijericnkii.

PMID- 28762643
TI  - Potential secondary poisoning risks to non-targets from a sodium nitrite toxic
      bait for invasive wild pigs.
AB  - BACKGROUND: An acute and orally delivered toxic bait containing micro
      encapsulated sodium nitrite (MESN), is under development to provide a novel and
      humane technology to help curtail damage caused by invasive wild pigs (Sus
      scrofa). We evaluated potential secondary risks for non-target species by:
      testing whether four different types of micro-encapsulation coatings could reduce
      vomiting by invasive wild pigs, testing the levels of residual sodium nitrite
      (SN) in tissues of invasive wild pigs, testing the environmental persistence of
      SN in vomitus, and conducting a risk assessment for scavengers. RESULTS: Micro
      encapsulation coatings did not affect the frequency of vomiting. We identified no
      risk of secondary poisoning for non-target scavengers that consume muscle, eyes,
      and livers of invasive wild pig carcasses because residual SN from the toxic bait
      was not detected in those tissues. The risk of secondary poisoning from consuming
      vomitus appeared low because ~90% of the SN was metabolized or broken down prior
      to vomiting, and continued to degrade after being exposed to the environment.
      Secondary poisoning could occur for common scavengers that consume approximately
      >=15% of their daily dietary requirements of digestive tract tissues or
      undigested bait from carcasses of invasive wild pigs in a rapid, single-feeding
      event. The likelihood of this occurring in a natural setting is unknown. The
      digestive tracts of poisoned invasive wild pigs contained an average of ~4.35
      mg/g of residual SN. CONCLUSION: Data from this study suggest no risks of
      secondary poisoning for non-target species (including humans) that consume
      muscle, liver, or eyes of invasive wild pigs poisoned with a MESN toxic bait.
      More species-specific testing for scavengers that consume digestive tract tissues
      and undigested bait is needed to reduce uncertainty about these potential risks.
      (c) 2017 Society of Chemical Industry.

PMID- 28762644
TI  - Hindered Amine Light Stabilizers Increase the Stability of Methylammonium Lead
      Iodide Perovskite Against Light and Oxygen.
AB  - Methylammonium lead iodide perovskite (MAPI) is a promising material for highly
      efficient photovoltaic devices. However, it suffers from photooxidation, which
      imposes strict requirements for its protection from oxygen during processing and
      operation. A hindered amine light stabilizer (HALS) has been found to exert a
      stabilization effect on methylammonium iodide (MAI) and MAPI against
      photooxidation. The HALS prevents the degradation of MAI by inhibiting the
      oxidation of iodide to iodine. Chemical modification of HALS allows its
      incorporation in MAPI films, which extends the resistivity of MAPI against
      photodegradation in ambient air from a couple of hours to several days, while
      causing no significant changes in key properties, such as optical absorption and
      charge transport. These results represent an important advance in the
      stabilization of MAPI against decomposition and demonstrate for the first time
      that antioxidants improve the stability of MAPI.

PMID- 28762645
TI  - Efficacy and tolerability of a double-conjugated retinoid cream vs 1.0% retinol
      cream or 0.025% tretinoin cream in subjects with mild to severe photoaging.
AB  - BACKGROUND: Topical retinoids are used to treat the visible signs of photoaging.
      While efficacious, they are irritating. OBJECTIVE: Evaluate the effectiveness and
      tolerability of a double-conjugate retinoid cream (AlphaRet Overnight Cream; AHA
      Ret) in improving visible signs of photoaging vs 1.0% retinol or 0.025%
      tretinoin. METHODS: A 12-week, split-face, randomized trial was conducted in 48
      female subjects, aged 30-65 years with mild to severe photodamage. AHA-Ret was
      applied to one side of the face and either retinol (n=24) or tretinoin (n=24) to
      the other side (PM). Expert blinded evaluation of images and Nova measurements
      occurred at 4, 8, and 12 weeks. Tolerability was assessed throughout the study.
      RESULTS: Forty-seven subjects completed the study. AHA-Ret demonstrated
      significant reductions in average severity from baseline: Fine Lines/Wrinkles
      (P<.001; all time points); Erythema (P=.004, P<.0001; 8 and 12 weeks,
      respectively); Dyschromia (P<.0001; all time points); Skin Tone (P<.0001; all
      time points), and Pore Size (P=.035, P<.0001; 8 and 12 weeks, respectively). AHA
      Ret induced less Erythema vs retinol at 8 (P=.008) and 12 (P<.02) weeks. AHA-Ret
      was noninferior to prescription tretinoin in all categories at 4 and 8 weeks, and
      for Fine Lines/Wrinkles, Erythema, Dyschromia, and Skin Tone at 12 weeks.
      Improvements in Hydration occurred at every time point with AHA-Ret only (P<.04,
      P<.03, P<.01). Less irritation was reported with AHA-Ret vs retinol or tretinoin.
      CONCLUSIONS: Treatment with a double-conjugate retinoid cream demonstrated early
      reductions in photodamage and improvements in Hydration. AHA-Ret induced less
      Erythema vs retinol and was more tolerable vs retinol and tretinoin.

PMID- 28762646
TI  - Predicting unplanned readmissions to a pediatric cardiac intensive care unit
      using predischarge Pediatric Early Warning Scores.
AB  - OBJECTIVE: Unplanned readmission to the pediatric cardiac intensive care unit
      (CICU) is associated with significant morbidity and mortality. The Pediatric
      Early Warning Score (PEWS) predicts ward patients at risk for decompensation but
      has not been previously reported to identify at-risk patients with cardiac
      disease prior to ward transfer. This study aimed to determine whether PEWS prior
      to transfer may serve as a predictor of unplanned readmission to the CICU.
      DESIGN: All patients discharged from a tertiary children's hospital CICU from
      September 2012 through August 2015 were included for analysis. PEWS assessment
      was performed following transfer to the cardiac ward, and starting in January
      2014, PEWS scores were also assigned by bedside CICU nurse prior to transfer from
      the CICU. Scores exceeding a predetermined threshold prompted further stability
      assessment by provider team prior to transfer. RESULTS: Among 1320 discharges of
      1082 patients during the study period, there were 130 unplanned readmissions
      during their hospitalization. Following implementation of pretransfer PEWS
      scoring, there was no significant reduction in unplanned readmission frequency
      (10.2% vs 9.2%, P = .39). A secondary analysis of PEWS scores revealed cardiac
      scoring as a strong discriminator of those likely to experience an unplanned
      readmission, independent of other significant clinical predictors of readmission
      (OR 1.78, 95% CI 1.17-2.71, P = .007). The resultant multivariate model was a
      good predictor of unplanned readmission (AUC 0.77, 95% CI 0.71-0.83, P < .001).
      CONCLUSION: While implementation of a pretransfer PEWS assessment did not reduce
      the frequency of unplanned readmissions in this small single-center cohort, a
      multivariate model including pretransfer elements of an early warning scoring
      system, along with other patient characteristics serves as a good discriminator
      of patients likely to experience an unplanned readmission following CICU
      discharge. Further prospective investigation is needed to define objective
      measures of pretransfer discharge readiness to potentially reduce the likelihood
      of unplanned readmissions.

PMID- 28762647
TI  - Renal histology in Indigenous Australians with lupus nephritis.
AB  - BACKGROUND: Lupus nephritis (LN) is a feared complication of systemic lupus
      erythematosus (SLE). Renal biopsy is valuable to assess disease severity and
      prognosis, but no histological data are available for Indigenous Australians
      (IA). We compared histopathology between IA and non-IA patients (NI) with LN in
      northern Australia and describe main outcomes. METHODS: Retrospective cohort
      study of all patients with biopsy evidence of LN at Royal Darwin Hospital over a
      10-year period. Biopsies were classified by International Society of Nephrology
      criteria with clinical finding and vital status obtained from electronic health
      records. Data analyses used Australian Bureau of Statistics 2011 census
      population, nonparametric testing and lifetable estimates. RESULTS: The study
      cohort contained 42 patients (mean age 30 years,86% female and 74% IA). The
      estimated annual incidence of biopsy-proven LN was 7/100 000 for IA versus
      0.7/100 000 for NI (P < 0.01). More IA patients had full-house immune complex
      deposition (79% vs. 21%, P < 0.05), but fewer IA patients had proliferative LN
      (classes III + IV) (42% vs. 72%) (P < 0.01). Five and 10-year patient (69% and
      50%) and renal survival (87% and 53%) in IA were much worse than for NI patients.
      The reported causes of death were infections (38.6%), end-stage renal disease
      (23%), cardiovascular events (15.4%). CONCLUSION: Indigenous Australians more
      frequently have histological evidence of LN with a broader spectrum of immune
      complex deposition but less severe renal inflammation compared to non-Indigenous
      patients. The relative contribution of LN to reduced patient and renal survival
      for Indigenous Australians thus requires further study.

PMID- 28762648
TI  - Directed Differentiation of Human Embryonic Stem Cells to Neural Crest Stem
      Cells, Functional Peripheral Neurons, and Corneal Keratocytes.
AB  - Neural crest stem cells (NCSCs) are a transient and multipotent cell population
      giving rise to various cell types with clinical importance. Isolation of human
      NCSCs is extremely challenging that limits our knowledge about neural crest
      development and application. Here, a defined protocol to efficiently direct human
      embryonic stem cells (hESCs) to NCSCs and multiple neural crest lineages is
      presented. A unique combination of small molecule inhibitors and growth factors
      is employed to generate NCSCs from hESCs through a neuroectoderm stage. The self
      renewal and multipotent capacities of hESC-derived NCSCs are assessed
      subsequently. In the feeder-free system, hESC-derived NCSCs (P75+ /HNK1+
      /AP2alpha+ /PAX6- ) in high purity are efficiently generated following
      neuroectodermal restriction. They can be propagated and differentiated toward
      multiple neural crest lineages in vitro, such as functional peripheral neurons
      (beta-tubulin III+ /peripherin+ ), mesenchymal stem cells (CD73+ CD90+ CD105+ ),
      and corneal keratocytes (keratocan+ ). The in vivo developmental potential of
      hESC-derived NCSCs is confirmed using zebrafish embryos. This report is the first
      demonstration of efficient differentiation of hESCs into corneal keratocytes as a
      monolayer in a feeder-free system. Considering the high efficacy of NCSC
      generation, this new method will be a useful tool for future clinical organ
      repair and regeneration, such as peripheral nerve regeneration and corneal
      repair.

PMID- 28762649
TI  - Associations between systemic bone mineral density, knee cartilage defects and
      bone marrow lesions in patients with knee osteoarthritis.
AB  - AIM: The relationship between bone mineral density (BMD) and osteoarthritis (OA)
      remains controversial. This study aimed to explore the cross-sectional
      associations between BMD at the total body, hip and spine and joint structural
      abnormalities including cartilage defects and bone marrow lesions (BMLs) in
      patients with knee OA. METHOD: One hundred and eight-five subjects with
      symptomatic knee OA were included in this study. T2-weighted fast spin echo
      magnetic resonance imaging was used to assess knee cartilage defects and BMLs.
      Total body, hip and spine BMD were measured using dual-energy X-ray
      absorptiometry. RESULTS: After adjustment for potential confounders, total hip
      BMD was negatively associated with medial tibial cartilage defects, lateral
      femoral cartilage defects, medial tibial BMLs and lateral tibial BMLs. Spine and
      total body BMD were negatively associated with lateral femoral cartilage defects,
      but not with BMLs. CONCLUSION: We concluded that BMD particularly at the hip was
      negatively associated with knee cartilage defects and BMLs.

PMID- 28762650
TI  - Ancient and modern: hints of a core post-transcriptional network driving
      chemotherapy resistance in ovarian cancer.
AB  - RNA-binding proteins (RBPs) and noncoding (nc)RNAs (such as microRNAs, long
      ncRNAs, and others) cooperate within a post-transcriptional network to regulate
      the expression of genes required for many aspects of cancer behavior including
      its sensitivity to chemotherapy. Here, using an RBP-centric approach, we explore
      the current knowledge surrounding contributers to post-transcriptional gene
      regulation (PTGR) in ovarian cancer and identify commonalities that hint at the
      existence of an evolutionarily conserved core PTGR network. This network
      regulates survival and chemotherapy resistance in the contemporary context of the
      cancer cell. There is emerging evidence that cancers become dependent on PTGR
      factors for their survival. Further understanding of this network may identify
      innovative therapeutic targets as well as yield crucial insights into the hard
      wiring of many malignancies, including ovarian cancer. WIREs RNA 2018, 9:e1432.
      doi: 10.1002/wrna.1432 This article is categorized under: RNA Interactions with
      Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications
      Translation > Translation Mechanisms RNA in Disease and Development > RNA in
      Disease.

PMID- 28762651
TI  - Provision of pharmaceutical care by community pharmacists across Europe: Is it
      developing and spreading?
AB  - RATIONALE, AIMS, AND OBJECTIVES: Pharmaceutical care involves patient-centred
      pharmacist activity to improve medicines management by patients. The
      implementation of this service in a comprehensive manner, however, requires
      considerable organisation and effort, and indeed, it is often not fully
      implemented in care settings. The main objective was to assess how pharmaceutical
      care provision within community pharmacy has evolved over time in Europe. METHOD:
      A cross-sectional questionnaire-based survey of community pharmacies, using a
      modified version of the Behavioural Pharmaceutical Care Scale (BPCS) was
      conducted in late 2012/early 2013 within 16 European countries and compared with
      an earlier assessment conducted in 2006. RESULTS: The provision of comprehensive
      pharmaceutical care has slightly improved in all European countries that
      participated in both editions of this survey (n = 8) with progress being made
      particularly in Denmark and Switzerland. Moreover, there was a wider country
      uptake, indicating spread of the concept. However, due to a number of
      limitations, the results should be interpreted with caution. Using combined data
      from participating countries, the provision of pharmaceutical care was positively
      correlated with the participation of the community pharmacists in patient-centred
      activities, routine use of pharmacy software with access to clinical data,
      participation in multidisciplinary team meetings, and having specialized
      education. CONCLUSIONS: The present study demonstrated a slight evolution in self
      reported provision of pharmaceutical care by community pharmacists across Europe,
      as measured by the BPCS. The slow progress suggests a range of barriers, which
      are preventing pharmacists moving beyond traditional roles. Support from
      professional bodies and more patient-centred community pharmacy contracts,
      including remuneration for pharmaceutical care services, are likely to be
      required if quicker progress is to be made in the future.

PMID- 28762654
TI  - Development of a high-performance liquid chromatography procedure to identify
      known and detect novel C-13 oligosaccharide moieties in diterpene glycosides from
      Stevia rebaudiana (Bertoni) Bertoni (Asteraceae): Structure elucidation of
      rebaudiosides V and W.
AB  - As an aid for structure elucidation of new steviol glycosides, reversed-phase C18
      high-performance liquid chromatography method was developed with several
      previously characterized diterpene glycosides, to identify known and detect novel
      aglycone-C13 oligosaccharide moieties and indirectly identify C-19 interlinkages.
      Elution order of several diterpene glycosides and their aglycone-C13
      oligosaccharide substituted with different sugar arrangements were also
      summarized. Comparison of the retention time of a product obtained after alkaline
      hydrolysis with the aglycone-C-13 portions of known compounds reported herein
      allowed us to deduce the exact positions of the sugars in the C-13
      oligosaccharide portion. The elution position of several steviol glycosides with
      an ent-kaurene skeleton was helpful to describe an identification key. Two
      previously uncharacterized diterpene glycosides together with two known compounds
      were isolated from a commercial Stevia rebaudiana leaf extract. One was found to
      be 13-[(2-O-beta-d-xylopyranosyl-3-O-beta-d-glucopyranosyl-beta-d
      glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid-(2-O-beta-d-glucopyranosyl-beta-d
      glucopyranosyl) ester (rebaudioside V), whereas the other was determined to be 13
      [(2-O-beta-d-xylopyranosyl-3-O-beta-d-glucopyranosyl-beta-d
      glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid-(2-O-alpha-l-rhamnopyranosyl-3-O
      beta-d-glucopyranosyl-beta-d-glucopyranosyl) ester (rebaudioside W). Previously
      reported compounds were isolated in gram quantities and identified as
      rebaudioside J and rebaudioside H. In addition, a C-19 sugar-free derivative was
      also prepared from rebaudioside H to afford rebaudioside H1 . Chemical structures
      were partially determined by the high-performance liquid chromatography method
      and unambiguously characterized by using one-dimensional and two-dimensional
      nuclear magnetic resonance experiments.

PMID- 28762653
TI  - Single cell transcriptomics of noncoding RNAs and their cell-specificity.
AB  - Recent developments of single cell transcriptome profiling methods have led to
      the realization that many seemingly homogeneous cells have surprising levels of
      expression variability. The biological implications of the high degree of
      variability is unclear but one possibility is that many genes are restricted in
      expression to small lineages of cells, suggesting the existence of many more cell
      types than previously estimated. Noncoding RNA (ncRNA) are thought to be key
      parts of gene regulatory processes and their single cell expression patterns may
      help to dissect the biological function of single cell variability. Technology
      for measuring ncRNA in single cell is still in development and most of the
      current single cell datasets have reliable measurements for only long noncoding
      RNA (lncRNA). Most works report that lncRNAs show lineage-specific restricted
      expression patterns, which suggest that they might determine, at least in part,
      lineage fates and cell subtypes. However, evidence is still inconclusive as to
      whether lncRNAs and other ncRNAs are more lineage-specific than protein-coding
      genes. Nevertheless, measurement of ncRNAs in single cells will be important for
      studies of cell types and single cell function. WIREs RNA 2017, 8:e1433. doi:
      10.1002/wrna.1433 For further resources related to this article, please visit the
      WIREs website.

PMID- 28762655
TI  - Knowledge and practice of, and attitudes toward, pulp therapy in deciduous teeth
      among pediatric dentists in India.
AB  - AIM: The aim of the present study was to assess the knowledge and practice of,
      and attitudes toward, pulp therapy in deciduous dentition among pediatric
      dentists. METHODS: A cross-sectional, observational survey was conducted using a
      closed-ended, multiple-choice questionnaire evaluating the knowledge and practice
      of, and attitudes toward, pulp therapy in deciduous dentition, which was
      formulated and sent to 360 pediatric dentists across India. Descriptive
      statistics were done, followed by chi2 -test to test the association between
      years of experience and the questionnaire items. RESULTS: A total of 3.5% of
      pediatric dentists performed their treatment using a rubber dam in all cases; 30%
      preferred to use local anesthesia prior to indirect pulp therapy (IPT).
      Traditional indirect pulp capping was preferred to IPT, and only 48% of them
      believed in not removing it completely. Pulpotomy was preferred over IPT (70%)
      when there was a probability of pulp exposure following complete caries
      excavation. Calcium hydroxide, along with iodoform, was the material of choice
      for the obturation of primary teeth (73.5%). A stainless steel crown was placed
      after pulp therapy in the primary tooth (86.3%). Most dentists believed requested
      immediate and 3-month follow up. CONCLUSION: The survey helps in assessing
      whether our views or approaches are in line with recent trends.

PMID- 28762656
TI  - Dub3 controls DNA damage signalling by direct deubiquitination of H2AX.

PMID- 28762657
TI  - Significant re-emergence and recirculation of Schmallenberg virus in previously
      exposed dairy herds in Ireland in 2016.
AB  - Schmallenberg virus (SBV) circulation was investigated in 25 previously exposed
      dairy herds in Ireland in 2016. A population of 1,550 spring-2014-born animals,
      which had been monitored for SBV infection in 2014 and 2015 as part of a previous
      SBV surveillance study, were resampled for evidence of SBV infection during 2016.
      A total of 366 blood samples were collected in the 25 study herds (15 samples per
      herd) between 3 March 2017 and 10 March 2017 (before the 2017 vector-active
      season) and analysed for SBV antibodies using a competitive ELISA kit (IDVet). A
      total of 256 animals tested seropositive, an AP of 69.9% (95% CI: 65.1-74.4) and
      TP of 77.7% (95% CI: 72.3%-82.8%) when correcting for imperfect test
      characteristics. These results demonstrate that a new epidemic of SBV circulation
      occurred in these previously exposed herds in Ireland in 2016.

PMID- 28762652
TI  - HIV incidence in the Estonian population in 2013 determined using the HIV-1
      limiting antigen avidity assay.
AB  - OBJECTIVES: Estonia has one the highest number of new HIV diagnoses in the
      European Union, mainly among injecting drug users and heterosexuals. Little is
      known of HIV incidence, which is crucial for limiting the epidemic. Using a
      recent HIV infection testing algorithm (RITA) assay, we aimed to estimate HIV
      incidence in 2013. METHODS: All individuals aged >=18 years newly-diagnosed with
      HIV in Estonia January- December 2013, except blood donors and those undergoing
      antenatal screening, were included. Demographic and clinical data were obtained
      from the Estonian Health Board and the Estonian HIV-positive patient database.
      Serum samples were tested for recent infection using the LAg-avidity EIA assay.
      HIV incidence was estimated based on previously published methods. RESULTS: Of
      69,115 tested subjects, 286 (0.41%) were newly-diagnosed with HIV with median age
      of 33 years (IQR: 28-42) and 65% male. Self-reported routes of HIV transmission
      were mostly heterosexual contact (n = 157, 53%) and injecting drug use (n = 62,
      21%); 64 (22%) were with unknown risk group. Eighty two (36%) were assigned
      recent, resulting in estimated HIV incidence of 0.06%, corresponding to 642 new
      infections in 2013 among the non-screened population. Incidence was highest
      (1.48%) among people who inject drugs. CONCLUSIONS: These high HIV incidence
      estimates in Estonia call for urgent action of renewed targeted public health
      promotion and HIV testing campaigns.

PMID- 28762658
TI  - Do antiemetic drugs benefit adult emergency department patients with nausea? The
      literature says no, but is it right?
AB  - Nausea is a common problem in ED patients. Antiemetic drugs have been used in the
      ED for decades, but a recent Cochrane review found no convincing evidence for the
      benefit of antiemetic drugs over placebo. This was largely based on three placebo
      controlled trials, which found mean Visual Analog Scale (VAS) changes for various
      drugs and placebo, to be similar. However, reliance on mean VAS change as the
      primary outcome measure has probably been a mistake. It does not give information
      on the number of improved patients, so these cannot be compared between groups.
      Alternative primary outcome measures warrant further exploration. Use of a VAS
      cut-off level indicative of clinically significant symptom improvement would
      allow comparison of numbers of patients with improved nausea ratings. This is
      proposed as the best option currently available. Preliminary testing of this
      outcome measure suggests that the conclusions of past studies may be misleading,
      and that the question of antiemetic efficacy for ED patients is not yet answered.

PMID- 28762659
TI  - Timing of surgical intervention for fungal infective endocarditis.

PMID- 28762660
TI  - Effect of pre existing respiratory conditions on survival of lung cancer
      patients: A nationwide population-based cohort study.
AB  - BACKGROUND: Common diseases with potential to increase the risk of death from
      lung cancer have so far not been studied in large populations. METHODS: We did a
      population-based retrospective cohort study using nationwide health insurance
      claims data from 2005 to 2012 in Korea including 205 403 lung cancer patients.
      Multivariate-adjusted hazard ratios (aHRs) of lung cancer mortality by presence,
      time intervals with lung cancer diagnosis and combinations of pre-existing
      chronic obstructive pulmonary disease (COPD), pneumonia, asthma and tuberculosis
      were calculated using the Cox-proportional hazards model. RESULTS: The total
      number of person-years of follow-up was 397 780 and 60.2% of patients died (mean
      survival 23.2 months after lung cancer diagnosis). Lung cancer patients with
      previous respiratory disease had increased aHR for mortality (COPD, hazard ratio
      [HR] = 1.32, CI 1.29-1.35; pneumonia, HR = 1.14, CI 1.08-1.19; and asthma, HR =
      1.11, CI 1.06-1.16). Risks were positively associated with longer duration of pre
      existing disease diagnosis; cases with >5 years since diagnosis compared to <2
      years: COPD, HR = 2.91, CI 2.82-3.00; pneumonia, HR = 1.67, CI 1.51-1.85; asthma,
      HR = 1.56, CI 1.45-1.68; and tuberculosis, HR = 2.03, CI 1.90-2.17. Furthermore,
      elevated HRs of death were found among patients with multiple pre-existing co
      morbidities. CONCLUSION: Hazards of death from lung cancer are significantly
      increased in cases with pre-existing lung disease, and worse with longer
      durations, and with multiple combinations before cancer diagnosis. Patients and
      physicians should be aware of these meaningful risk/prognostic factors for lung
      cancer when identifying high-risk patient groups.

PMID- 28762661
TI  - Morning dosing for dolutegravir-related insomnia and sleep disorders.

PMID- 28762663
TI  - Impact of Monopolar TURP, Bipolar TURP and Photoselective Vaporization of
      Prostate for Enlarged Prostate on Erectile Function.
AB  - OBJECTIVES: To compare monopolar transurethral resection of the prostate (TURP),
      bipolar TURP and photoselective vaporization of the prostate (PVP) by 120-W
      GreenLight laser with regard to the impact on International Index of Erectile
      Function (IIEF)-5 score in patients presenting with lower urinary tract symptoms
      (LUTS) secondary to prostate >80 mL. METHODS: Between April 2012 and March 2015,
      110 patients who satisfied eligibility criteria were divided into three groups
      according to surgical modality adopted to treat benign prostatic enlargement.
      Preoperative, perioperative, and follow-up data were collected. The three groups
      were as follows: group A, monopolar TURP; group B, bipolar TURP; and group C,
      PVP. RESULTS: The baseline characteristics of the three groups were similar. All
      the perioperative parameters were significantly favorable in group C compared
      with the other two groups, except for mean operative time, which was
      significantly higher in group C. International Prostate Symptom Score, postvoid
      residual urine, maximum flow rate and quality of life score had significant and
      similar improvement during follow up in all three groups. Also, prostate volume
      reduced significantly in all three groups following surgery, but it remained
      significantly higher in group C patients compared with groups A and B. Mean IIEF
      5 score was similar between the three groups at baseline and during each of the
      follow-up visits. Groups A, B and C had declines of 3.27% (P = 0.34), 2.68% (P =
      0.40) and 3.36% (P = 0.35), respectively, in mean IIEF-5 score at 12-month follow
      up compared with baseline. CONCLUSIONS: Monopolar TURP, bipolar TURP and PVP by
      120-W GreenLight laser for prostate size >80 mL do not have a significant impact
      on IIEF-5 score at 12-month follow up.

PMID- 28762662
TI  - Social motivation and implicit theory of mind in children with autism spectrum
      disorder.
AB  - : According to the social motivation theory of autism, children who develop
      Autism Spectrum Disorder (ASD) have early deficits in social motivation, which is
      expressed by decreased attention to social information. These deficits are said
      to lead to impaired socio-cognitive development, such as theory of mind (ToM).
      There is little research focused on the relation between social motivation and
      ToM in this population. The goal of the present study was to investigate the link
      between one aspect of social motivation, social orienting, and ToM in
      preschoolers with ASD. It was expected that, in contrast to typically developing
      (TD) children, children with ASD would show impaired performance on tasks
      measuring social orienting and ToM. It was also expected that children's
      performance on the social orienting tasks would be correlated with their
      performance on the ToM task. A total of 17 children with ASD and 16 TD children
      participated in this study. Participants completed two social orienting tasks, a
      face preference task and a biological motion preference task, as well an implicit
      false belief task. Results reveal that TD children, but not children with ASD,
      exhibited social preference as measured by a preference for faces and biological
      motion. Furthermore, children with ASD tended to perform worse on the ToM task
      compared to their TD counterparts. Performance on the social motivation tasks and
      the ToM task tended to be related but only for the TD children. These findings
      suggest that ToM is multifaceted and that motivational deficits might have
      downstream effects even on implicit ToM. Autism Res 2017, 10: 1834-1844. (c) 2017
      International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY:
      The goal of the present study was to examine the link between poor attention to
      social information and mindreading abilities in children with autism spectrum
      disorder (ASD). Results demonstrated that children with ASD tended to perform
      worse than neurotypical children on both social orienting and theory of mind
      tasks. Preference for human faces and motion tended to be related but only for
      the neurotypical children. These findings provide partial support for the social
      motivation theory.

PMID- 28762664
TI  - Selective Semihydrogenation of Alkynes Catalyzed by Pd Nanoparticles Immobilized
      on Heteroatom-Doped Hierarchical Porous Carbon Derived from Bamboo Shoots.
AB  - Highly dispersed palladium nanoparticles (Pd NPs) immobilized on heteroatom-doped
      hierarchical porous carbon supports (N,O-carbon) with large specific surface
      areas are synthesized by a wet chemical reduction method. The N,O-carbon derived
      from naturally abundant bamboo shoots is fabricated by a tandem hydrothermal
      carbonization process without assistance of any templates, chemical activation
      reagents, or exogenous N or O sources in a simple and ecofriendly manner. The
      prepared Pd/N,O-carbon catalyst shows extremely high activity and excellent
      chemoselectivity for semihydrogenation of a broad range of alkynes to versatile
      and valuable alkenes under ambient conditions. The catalyst can be readily
      recovered for successive reuse with negligible loss in activity and selectivity,
      and is also applicable for practical gram-scale reactions.

PMID- 28762666
TI  - Developmental toxicity evaluation of Pimenta pseudocaryophyllus (Gomes) Landrum,
      (E)-methyl isoeugenol chemotype, in Wistar rats.
AB  - BACKGROUND: Pimenta pseudocaryophyllus (Gomes) Landrum (Myrtaceae) has been
      traditionally used in Brazilian folk medicine. Studies have established the
      botanical characterization, phytochemistry profile, and pharmacological potential
      of this species, including antibiotic, anxiolytic, antidepressant, antioxidant,
      antinociceptive, and anti-inflammatory properties. Despite its widespread use, no
      previous study has been conducted regarding its toxicological profile, especially
      during pregnancy. Thus, this study investigated the developmental toxicity of the
      dry leaf extract of the P. pseudocaryophyllus, (E)-methyl isoeugenol chemotype,
      in rats. METHODS: First, the dry leaf extract was prepared by a spray-drying
      technique. Then, pregnant Wistar rats were orally treated with dry extract at
      doses of 0, 2000, 2500, or 3000 mg/kg from gestational day 6 through 15
      (organogenesis period). On gestational day 21, the rats underwent cesarean
      sections and the reproductive outcomes and biochemistry parameters related to
      hepatic and renal markers were evaluated. Additionally, the fetuses were examined
      for external and skeletal variations and malformations. RESULTS: The spray-drying
      technique preserved the phytocomplex components and showed a satisfactory yield.
      No relevant differences were seen in the food consumption, reproductive
      performances, and hepatic and renal biochemical parameters between groups.
      However, there was a decrease in body weight gain of the dams during the
      organogenesis period and an increase of minor skeletal variations in the
      offspring (increased fetal incidences only of delayed ossification of the
      metacarpals, metatarsals, phalanges, sternebra, and rudimentary ribs) treated
      with the dry extract. CONCLUSION: The extract of P. pseudocaryophyllus, (E)
      methyl isoeugenol chemotype, showed low maternal toxicity and induced minor
      skeletal variations in the offspring. Birth Defects Research 109:1292-1300, 2017.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 28762665
TI  - External validation of the DASH prediction rule: a retrospective cohort study.
AB  - : Essentials Predicting recurrences may guide therapy after unprovoked venous
      thromboembolism (VTE). We evaluated the DASH score in 827 patients with
      unprovoked VTE to verify prediction accuracy. A DASH score <= 1 had a cumulative
      recurrence risk at 1 year of 3.6%, as predicted by the model. The DASH score
      performed better in younger (< 65 years old) subjects. SUMMARY: Background The
      DASH prediction model has been proposed as a guide to identify patients at low
      risk of recurrence of venous thromboembolism (VTE), but has never been validated
      in an independent cohort. Aims To validate the calibration and discrimination of
      the DASH prediction model, and to evaluate the DASH score in a predefined patient
      subgroup aged > 65 years. Methods Patients with a proximal unprovoked deep vein
      thrombosis (DVT) or pulmonary embolism (PE) who received a full course of vitamin
      K antagonist or direct oral anticoagulant (> 3 months) and had D-dimer measured
      after treatment withdrawal were eligible. The DASH score was computed on the
      basis of the D-dimer level after therapy withdrawal and personal characteristics
      at the time of the event. Recurrent VTE events were symptomatic proximal or
      distal DVT/PE, and were analyzed with a time-dependent analysis. Observed 12
      month and 24-month recurrence rates were compared with recurrence rates predicted
      by the DASH model. Results We analyzed a total of 827 patients, of whom 100
      (12.1%) had an objectively documented recurrence. As compared with the original
      DASH cohort, there was a greater proportion of subjects with a 'low-risk' (<= 1)
      DASH score (66.3% versus 51.6%, P < 0.001). The slope of the observed versus
      expected cumulative incidence at 2 years was 0.71 (95% confidence interval 0.51
      1.45). The c-statistic was lower for subjects aged > 65 years (0.54) than for
      younger subjects (0.72). Conclusions These results confirm the validity of DASH
      prediction model, particularly in young subjects. The recurrence risk in elderly
      patients (> 65 years) was, however, > 5% even in those with the lowest DASH
      scores.

PMID- 28762667
TI  - Reproductive and Neurobehavioral Effects of Ethiprole Administered to Mice in the
      Diet.
AB  - BACKGROUND: Few studies were found for neurobehavioral toxicity of the
      phenylpyrazole insecticide ethiprole in mammals. This study was designed to
      evaluate the reproductive and neurobehavioral effects of ethiprole exposure in
      mice. METHODS: Ethiprole was given in the diet to provide levels of 0 (control),
      0.0003, 0.0009, and 0.0027% from 5 weeks of age of the F0 generation to 11 weeks
      of age of the F1 generation in mice. Selected reproductive and neurobehavioral
      parameters were measured. RESULTS: Movement time increased with a significant
      dose-related trend, and frequencies of mice with urination increased in the high
      dose group of adult males in the F0 generation. The average body weight of male
      and female offspring increased significantly in treatment groups at postnatal
      days (PNDs) 7, 14, and 21. Surface righting on PND 7 of male offspring was
      accelerated in a significant dose-related trend. In female offspring, olfactory
      orientation on PND 14 was accelerated significantly on the route of higher-dose
      groups, and time of all treatment groups. Total distance, movement time, average
      speed, and average time of movement significantly decreased, and frequencies of
      mice with urination increased in a significant dose-related trend in male
      offspring in the F1 generation. Longitudinal patterns of spontaneous behavior
      differed in the number of horizontal activities, movement time, and average speed
      in treatment groups in males. The number of horizontal activities of females
      decreased in a significant dose-related trend through 120 min. CONCLUSION: The
      dose levels of ethiprole in the present study produced several adverse effects in
      neurobehavioral parameters in mice. Birth Defects Research 109:1568-1585, 2017.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 28762668
TI  - Luminescent properties of single-phase Ba2-x-1.5y-1.5z P2 O7 :xEu2+ ,yCe3+ ,
      zTb3+ phosphors for white light-emitting diode.
AB  - A series of Ba2 P2 O7 :xEu2+ ,yCe3+ ,zTb3+ phosphors was synthesized via a co
      precipitation method, then their crystal structure, quantum efficiency and
      luminescent properties were analyzed by XRD and FL, respectively. The results
      showed that these phosphors not only presented the excitation characteristics of
      Ba2 P2 O7 :xEu2+ ,zTb3+ , but also exhibited that of the Ba2 P2 O7 :yCe3+ ,zTb3+
      phosphor. Meanwhile, the tri-doped phosphor showed a stronger absorption around
      320 nm in contrast with the Eu2+ /Ce3+ :Tb3+ co-doped phosphor. Not only can
      energy transfer from Ce3+ ->Eu2+ be observed; the energy transfer mechanism from
      Eu2+ to Tb3+ is discussed in the tri-doped system. Ce3+ affects the luminescence
      properties of Ba2 P2 O7 :xEu2+ ,yCe3+ ,zTb3+ phosphors just as the sensitizer
      whereas Eu2+ is considered both as the sensitizer and the activator. The
      chromaticity coordinates of tri-doped phosphors excited at 320 nm stayed steadily
      in the bluish-white light region,and the emitted color and color temperature
      (CCT) of these phosphors could be tuned by adjusting the relative contents of
      Eu2+ , Ce3+ and Tb3+ . Hence, the single phase Ba2 P2 O7 :xEu2+ ,yCe3+ ,zTb3+
      phosphors may be considered as potential candidates for white light-emitting
      diodes.

PMID- 28762669
TI  - White spot lesions: Does etching really matter?
AB  - AIM: The clinical significance of acid etching prior to orthodontic bonding is
      controversial. In the present study, we evaluated the effect of 15 seconds of
      acid etching on enamel demineralization. METHODS: Twenty-seven human molars were
      sectioned and assigned to two groups. Under standardized conditions, the enamel
      surfaces were imaged using FluoreCam to obtain baseline data. Group 1 was etched
      using 37% phosphoric acid for 15 seconds, rinsed with water, and then imaged
      again; group 2 was only rinsed with water. Water rinse was collected for calcium
      chemical analysis using inductively-coupled plasma auger electron spectrometry.
      Both groups were subjected to 9 days of pH cycling, after which final FluoreCam
      images were obtained. RESULTS: Group 1 showed a significant increase in lesion
      area (P=.012), decrease in light intensity (P=.009), and decrease in impact
      (P=.007) after acid etching. The amount of calcium that leached out over the 15
      seconds was 14 ppm +/-2.4 (0.35 mmol/L+/-0.06). Following pH cycling, there was
      no statistically-significant between-group difference in overall enamel
      demineralization. CONCLUSION: Initial demineralization caused by 15 seconds of
      acid etching does not increase enamel susceptibility to further demineralization.
      This suggests that acid etching does not increase the risk of developing white
      spot lesions during orthodontics.

PMID- 28762670
TI  - Radiological Tenckhoff catheter insertion for peritoneal dialysis: A cost
      effective approach.
AB  - INTRODUCTION: Radiological insertion of Tenckhoff catheters can be an alternative
      option for peritoneal dialysis access creation, as compared to surgical catheter
      insertion. This study will review the outcomes and complications of radiological
      Tenckhoff catheter insertion in a metropolitan renal service and compare costs
      between surgical and radiological insertion. METHODS: Data were collected
      prospectively for all patients who had a Tenckhoff catheter insertion for
      peritoneal dialysis (PD) under radiological guidance at our hospital from May
      2014 to November 2016. The type of catheter used and complications, including
      peri-catheter leak, exit site infection and peritonitis were reviewed. Follow-up
      data were also collected at points 3, 6 and 12 months from catheter insertion.
      Costing data were obtained from Queensland Health Electronic Reporting System
      (QHERS) data, average staff salaries and consumable contract price lists.
      RESULTS: In the 30-month evaluation period, 70 catheters were inserted. Two
      patients had an unsuccessful procedure due to the presence of abdominal
      adhesions. Seven patients had an episode of peri-catheter leak, and four patients
      had an exit site infection following catheter insertion. Peritonitis was observed
      in nine patients during the study period. The majority of patients (90%) remained
      on peritoneal dialysis at 3-month follow-up. The average costs of surgical and
      radiological insertion were noted to be AUD$7788.34 and AUD$1597.35,
      respectively. CONCLUSION: Radiological Tenckhoff catheter insertion for
      peritoneal dialysis appears to be an attractive and cost-effective option given
      less waiting periods for the procedure, the relatively low cost of insertion and
      comparable rates of complications.

PMID- 28762671
TI  - Comparison of different polishing methods on the surface roughness of
      microhybrid, microfill, and nanofill composite resins.
AB  - AIM: The aim of the present study was to evaluate the effect of different
      polishing methods on the surface roughness of resin-based composites subjected to
      a thermocycling procedure. METHODS: A total of 192 specimens were divided into 24
      groups, according to composite materials (Filtek Z250, Point 4, Renamel Nanofill,
      Filtek Supreme Plus, Renamel Microfill, and Premise) and finishing and polishing
      systems (Sof-Lex Pop On, Super Snap, Flexidisc, and Flexidisc+Enamelize). The
      specimens were subjected to thermocycling (5000 cycles). RESULTS: Filtek Supreme
      Plus showed the lowest surface roughness values before thermocycling. After
      thermocycling, Filtek Supreme Plus continued to have the lowest surface
      roughness, with a statistically-significant difference for the other materials.
      After thermocycling, there was no statistically-significant difference among all
      the polishing techniques studied. CONCLUSIONS: The thermocycling was concluded as
      being able to change composite resins' surface roughness, whereas different
      finishing and polishing methods did not result in surface roughness changes after
      thermocycling.

PMID- 28762672
TI  - Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for
      Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a
      Japanese Post-Marketing Surveillance Study.
AB  - OBJECTIVES: To report interim 1-year results from a 3-year surveillance study
      evaluating safety, efficacy, and persistence of long-term mirabegron for
      overactive bladder (OAB). METHODS: Patients starting treatment with mirabegron
      for urinary urgency, daytime frequency, and urgency incontinence associated with
      OAB were registered and followed up for 3 years. Data were collected on adverse
      drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder
      Symptom Score (OABSS), and treatment discontinuations. Treatment persistence
      rates were calculated by Kaplan-Meier analysis. RESULTS: Eighty-one ADR were
      observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with
      the incidence highest during the first month. No significant change in residual
      urine volume was observed at any observation point up to 1 year of mirabegron
      treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1
      year/discontinuation. Total OABSS was decreased with statistical significance at
      3 months, 6 months, and 1 year, or at discontinuation (P < 0.001 at each time
      point). Kaplan-Meier treatment persistence rates were 84.8% at 3 months, 77.6% at
      6 months, and 66.0% at 1 year. Treatment persistence rates were similar for male
      and female patients but significantly higher for patients aged >=65 years (67.3%;
      n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P =
      0.032). CONCLUSIONS: Long-term OAB treatment with mirabegron was well-tolerated,
      with effectiveness maintained through 1 year. Mirabegron treatment persistence
      was higher than has been previously reported, and was greater in patients aged
      >=65 years compared with those aged <65 years.

PMID- 28762673
TI  - Interaction between Maternal and Paternal SHMT1 C1420T Predisposes to Neural Tube
      Defects in the Fetus: Evidence from Case-Control and Family-Based Triad
      Approaches.
AB  - BACKGROUND: Neural tube defects (NTDs) are caused by the failure of neural tube
      formation which occurs during early embryonic development. NTDs are the most
      severe and leading cause of fetal mortality. Serine hydroxymethyl transferase
      (SHMT1) provides one-carbon units necessary for embryogenesis and defects in one
      carbon production result in specific pathological conditions during pregnancy.
      The present study is aimed to evaluate the association of SHMT1 C1420T with NTD
      risk in the fetus using fetal, maternal and paternal groups by applying both case
      control and family-based triad approaches. METHODS: A total of 924 subjects
      including 124 NTD case-parent trios (n = 124 * 3 = 372) and 184 healthy control
      parent trios (n = 184 * 3 = 552) from Telangana State, South India were analyzed.
      DNA from umbilical cord tissues and parental blood samples were extracted, and
      genotyped by polymerase chain reaction-restriction fragment length polymorphism.
      Statistical analysis used were SPSS, parent-of-origin effect (POE) analysis.
      RESULTS: Case-control study design demonstrated fetuses with homozygous variant
      genotype (TT) to be at risk toward spina bifida subtype (p = 0.022). Among
      parents, fathers with TT genotype were associated with anencephaly (p = 0.018)
      and spina bifida subtypes (p = 0.027) in the offspring. Of interest, maternal
      paternal-offspring genotype incompatibility revealed maternal CT genotype in
      combination with paternal TT genotype increased risk for NTDs in the fetus (CTxTT
      = TT; p = 0.021). Family-based parent-of-origin effect linkage analysis revealed
      significant maternal over-transmission of variant allele to NTD fetuses (p <
      0.01). CONCLUSION: The present study, using both case-control and family-based
      triad approach is the first report to demonstrate parental association of SHMT1
      C1420T variant in conferring NTD risk in the fetus. Birth Defects Research
      109:1020-1029, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28762675
TI  - Major Birth Defects after Vaccination Reported to the Vaccine Adverse Event
      Reporting System (VAERS), 1990 to 2014.
AB  - BACKGROUND: Major birth defects are important infant outcomes that have not been
      well studied in the postmarketing surveillance of vaccines given to pregnant
      women. We assessed the presence of major birth defects following vaccination in
      the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous
      reporting system used to monitor the safety of vaccines in the United States.
      METHODS: We searched VAERS for reports of major birth defects during January 1,
      1990, through December 31, 2014. We excluded birth defects from vaccines that had
      been studied in pregnancy registries or other epidemiological studies (e.g.,
      human papilloma virus, varicella, measles/mumps/rubella, and anthrax vaccines).
      Birth defects were categorized into trimester of vaccination and classified based
      on the organs and/or systems affected. If several birth defects affecting
      different systems were described, we classified those as multiple body systems.
      Empirical Bayesian data mining was used to assess for disproportionate reporting.
      RESULTS: We identified 50 reports of major birth defects; in 28 reports, the
      vaccine was given during the first trimester; 25 were reports with single
      vaccines administered. Birth defects accounted for 0.03% of all reports received
      by VAERS during the study period and 3.2% of pregnancy reports; reported defects
      affected predominately the musculoskeletal (N = 10) or nervous (N = 10) systems.
      No unusual clusters or specific birth defects were identified. CONCLUSION: This
      review of the VAERS database found that major birth defects were infrequently
      reported, with no particular condition reported disproportionally. Birth defects
      after routine maternal vaccination will continue to be monitored in VAERS for
      signals to prompt future studies. Birth Defects Research 109:1057-1062, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28762674
TI  - Identifying Genetic Sources of Phenotypic Heterogeneity in Orofacial Clefts by
      Targeted Sequencing.
AB  - BACKGROUND: Orofacial clefts (OFCs), including nonsyndromic cleft lip with or
      without cleft palate (NSCL/P), are common birth defects. NSCL/P is highly
      heterogeneous with multiple phenotypic presentations. Two common subtypes of
      NSCL/P are cleft lip (CL) and cleft lip with cleft palate (CLP) which have
      different population prevalence. Similarly, NSCL/P can be divided into bilateral
      and unilateral clefts, with unilateral being the most common. Individuals with
      unilateral NSCL/P are more likely to be affected on the left side of the upper
      lip, but right side affection also occurs. Moreover, NSCL/P is twice as common in
      males as in females. The goal of this study is to discover genetic variants that
      have different effects in case subgroups. METHODS: We conducted both common
      variant and rare variant analyses in 1034 individuals of Asian ancestry with
      NSCL/P, examining four sources of heterogeneity within CL/P: cleft type, sex,
      laterality, and side. RESULTS: We identified several regions associated with
      subtype differentiation: cleft type differences in 8q24 (p = 1.00 * 10-4 ),
      laterality differences in IRF6, a gene previously implicated with wound healing
      (p = 2.166 * 10-4 ), sex differences and side of unilateral CL differences in
      FGFR2 (p = 3.00 * 10-4 ; p = 6.00 * 10-4 ), and sex differences in VAX1 (p < 1.00
      * 10-4 ) among others. CONCLUSION: Many of the regions associated with phenotypic
      modification were either adjacent to or overlapping functional elements based on
      ENCODE chromatin marks and published craniofacial enhancers. We have identified
      multiple common and rare variants as potential phenotypic modifiers of NSCL/P,
      and suggest plausible elements responsible for phenotypic heterogeneity, further
      elucidating the complex genetic architecture of OFCs. Birth Defects Research
      109:1030-1038, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28762676
TI  - Human-vehicle embodiment when predictability is violated.
AB  - Embodiment in human-vehicle interaction is higher for perceived safety than for
      perceived risk. When operational anticipations are violated, experiencing a
      vehicle as body-extension is negatively correlated with operational effort as
      indicated by neural activation in the motor system.

PMID- 28762677
TI  - Are the privacy rules on organ donation causing unnecessary grief?

PMID- 28762678
TI  - [Anticorruption in Syracuse, Italy].

PMID- 28762679
TI  - [Medicine and Nephrology from Social Networks].

PMID- 28762680
TI  - [Update on proteomic use in hemodialysis].
AB  - Application of proteomics has become one of the leading experimental disciplines
      for increased understanding of the key role played by proteins and protein
      protein interactions in all aspects of cell function. There is an increasing use
      of proteomic technologies for investigation into renal replacement therapy such
      as hemodialysis. In the last 10 years, the application of shotgun bottom-up
      liquid chromatography-mass spectrometry/mass spectrometry approaches has been
      successfully applied to research in uremic toxicity, with the discovery of novel
      uremic toxins and the potential to delineate a precise molecular approach to
      defining the biochemical nature of uremia. Major investigations of proteomics in
      hemodialysis therapy include molecular definition of uremic toxicity,
      identification of prognostic biomarkers, blood purification efficiency testing,
      and biocompatibility assessment of the dialyzer membrane materials. In this
      article, we review the results of recent proteoic investigations in the setting
      of chronic hemodialysis therapy.

PMID- 28762681
TI  - [Novel antiviral agents for the treatment of HCV among renal transplant
      recipients].
AB  - The frequency of hepatitis C virus infection remains high in renal transplant
      recipients and plays a detrimental role on survival in this population. According
      to the latest evidence, the adjusted relative risk of mortality and graft loss
      for anti-HCV seropositive versus anti-HCV negative renal transplant recipients
      was 1.85 with a 95% confidence interval (CI) of 1.49 ; 2.31 (P < 0.0001) and 1.76
      (95% CI, 1.46 ; 2.11) (P < 0.0001), respectively. Interferon-based regimens have
      been recommended for the treatment of hepatitis C after renal transplantation
      only in selected circumstances because of an increased risk of acute rejection
      due to the immuno-stimulatory properties of interferon. Limited data exist on the
      treatment of HCV with direct-acting antiviral agents among kidney transplant
      recipients. To date, the most important evidence comes from the European
      multicenter study where a large cohort (n=114) of patients with glomerular
      filtration rate of 40 mL/min/1.73m2 received an interferon-free, ribavirin-free
      combination of direct-acting antivirals (Ledipasvir/Sofosbuvir) for 12 or 24
      weeks. A high efficacy [SVR12 rate, 100% (114/114) ] was found even if three
      serious adverse were observed ; all were determined to be treatment related, one
      patient interrupted permanently treatment. Also, single-center single-arm
      observational studies have reported high efficacy and safety of sofosbuvir-based
      combinations for the treatment of HCV after renal transplant. A decline in
      through levels of calcineurin inhibitors after completion of antiviral therapy
      has been found in many patients; an enhanced metabolism of calcineurin inhibitors
      associated with resolution of liver injury has been suggested. An effective and
      safe therapy for HCV in kidney transplant recipients might improve the current
      suboptimal utilization of HCV-positive kidney donors and provide many patients
      with end-stage renal disease access to HCV-infected donor kidneys.

PMID- 28762682
TI  - [Use of citrate in patients with nephrolithiasis].
AB  - Citrate is a tricarboxylic acid and an intermediate metabolite of Krebs cycle. It
      contributes to oxidative metabolism of both kidney and liver. Alkaline sodium or
      potassium salts have the potential to increase alkaline reserve. In the kidney
      citrate is completely filtered at the glomerulus, undergoing to 10-40% tubular
      resorption. Renal insufficiency, even early, metabolic acidosis, potassium
      depletion induce hypocitraturia. Its importance in nephrolithiasis stems from its
      ability to form soluble complexes with calcium and to interfere with crystal
      formation, thus exerting a dual inhibition, thermodynamic and kinetic. Moreover,
      its alkalizing property has shown benefits of bone mineralization. The alkalizing
      effect is also useful in uric acid and cystine stone disease. Hypocitraturia has
      a significant incidence in the course of calcium nephrolithiasis, either
      secondary to aforementioned causes, or in idiopathic and/or familial forms.
      Citrate is used in the prevention of stone recurrences and given as tripotassic
      or potassium-magnesium salt, 0.1 mmol/kg/day in 2-3 dosages. In uric acid
      disease, in addition to prevention, it can induce dissolution of renal stones,
      provided urine pH is maintained at higher than 6.5 values. As concerns its
      effects on bone, it was shown to induce both decreases in marker of bone
      resorption and increases in bone mineral density.

PMID- 28762683
TI  - [Gross Hematuria after kidney biopsy. A case report].
AB  - We describe the clinical case of a patient experiencing severe gross hematuria
      causing clotting in the renal pelvis, after undergoing a kidney biopsy.The
      ecocolordopper and CT angiography performed did not reveal the cause of
      hematuria.The kidney arteriography allowed the diagnosis, revealing an
      arteriovenous fistula responsible for bleeding together with a small false
      aneurysm in the lower pole of the biopsied kidney. Both lesions were successfully
      treated with superselective embolization with microcoils. We discuss about the
      diagnostic and therapeutic approach of these rare post-biopsy complications
      briefly focusing on the technical aspects and on possible risks that the
      transcatheter embolotherapy may result.

PMID- 28762684
TI  - [The Retroperitoneal space].
AB  - We describe the case of a 45-year-old woman with a clinical history of breast
      cancer presenting with anuric renal failure, metabolic acidosis and bilateral
      grade 2-3 hydronephrosis. Following insertion of bilateral ureteral stents,
      urinary output was 5000 ml in the subsequent 24 hours with frankly bloody urine,
      after which anuria recurred. A new ultrasound examination showed hydronephrotic
      kidneys with properly positioned stents, a distended bladder free of clots and a
      hypo-anechoic, well-demarcated mass enveloping the aorta. With the echo color
      Doppler, injection of saline solution through a Foley catheter showed fluid flow
      similar to a ureteral jet within the bladder. Since the catheter balloon could
      not be sonographically visualized in the bladder we decided to re-examine this
      organ. Scans over what we thought was the bladder detected the balloon in a
      depleted bladder and fluid underlying it. CT urography revealed bilateral
      hydronephrosis secondary to a reperitoneal fibrous plaque surrounding the ureters
      and extending to the pelvic floor that had produced an encapsulated fluid
      collection. The clinical and imaging findings were strongly suggestive of acute
      obstructive renal failure secondary to retroperitoneal fibrosis. The
      retroperitoneal fluid collection, which had been mistaken for the bladder, may be
      due to a hematoma, aurinoma, an inflammatory process or a lymphocele.

PMID- 28762685
TI  - Fabry Disease in Southern Sardinia: epidemiological results from screening in an
      extensive area.
AB  - Introduction: Epidemiological data relating to the prevalence and incidence of
      Fabry disease (FD) and other Lysosomal Storage diseases (LSDs) are largely
      underestimated and not yet well known. Distribution of the disease varies
      according to geographical area and to ethnic origin. Heterozygous females are
      also at risk of contracting severe and multi-symptomatic forms of FD. Aim: To
      demonstrate the results obtained in outpatient surgeries situated in an area
      comprising 319,340 inhabitants. Methods: Out of a total of 2710 nephrologist
      visits, 150 patients with suspected FD (73 undergoing dialysis and 77
      conservative management) were selected. The relatives of one female patient on
      dialysis who had tested positive were investigated and a further 11 patients thus
      identified (total: 4 males and 7 females) within a micro-area of 21,822
      inhabitants, i.e. a prevalence rate of one positive case every 1,818 inhabitants.
      These data relate to the first 18 months of screening. Conclusions: In the field
      of nephrology, patients with high levels of proteinuria or microalbuminuria (150
      200 mg/day) should be screened for FD, particularly in areas with a high
      incidence and/or prevalence of kidney disease. Once positive patients of both
      sexes have been identified, they should immediately be referred for cardiologic
      and neurological assessment.

PMID- 28762687
TI  - Developmental Dysplasia of the Hip in Infants: A Clinical Report from the AAP on
      Evaluation and Referral.

PMID- 28762686
TI  - [Law on 'Informed Consent and Living Will': a critical review of latest approved
      text by Italian House of Representatives on 20 April 2017].

PMID- 28762688
TI  - Antipsychotics for Fibromyalgia in Adults.

PMID- 28762690
TI  - Antiplatelet vs. Anticoagulation Therapy for Patients with Heart Failure in Sinus
      Rhythm.

PMID- 28762689
TI  - Painless Nodular Rash in a Young Man.

PMID- 28762691
TI  - HIV-Associated Complications: A Systems-Based Approach.
AB  - Persons with human immunodeficiency virus (HIV) infection often develop
      complications related directly to the infection, as well as to treatment. Aging,
      lifestyle factors, and comorbidities increase the risk of developing chronic
      conditions such as diabetes mellitus and chronic kidney disease. HIV-associated
      neurologic complications encompass a wide spectrum of pathophysiology and
      symptomatology. Cardiovascular and pulmonary conditions are common among persons
      with HIV infection. Although some specific antiretroviral medications have been
      linked to disease development, traditional risk factors (e.g., smoking) have
      major roles. Prevention and management of viral hepatitis coinfection are
      important to reduce morbidity and mortality, and new anti-hepatitis C agents
      produce high rates of sustained virologic response. Antiretroviral-associated
      metabolic complications include dyslipidemia, hyperglycemia, and loss of bone
      mineral density. Newer options generally pose less risk of significant systemic
      toxicity and are better tolerated. Family physicians who care for patients with
      HIV infection have a key role in identifying and managing many of these chronic
      complications.

PMID- 28762693
TI  - Patients with Disabilities: Avoiding Unconscious Bias When Discussing Goals of
      Care.

PMID- 28762694
TI  - Pelvic Organ Prolapse.
AB  - Pelvic organ prolapse is the descent of one or more of the anterior vaginal wall,
      posterior vaginal wall, the uterus (cervix), or the apex of the vagina (vaginal
      vault or cuff scar after hysterectomy). Prevalence increases with age. The cause
      of prolapse is multifactorial but is primarily associated with pregnancy and
      vaginal delivery, which lead to direct pelvic floor muscle and connective tissue
      injury. Hysterectomy, pelvic surgery, and conditions associated with sustained
      episodes of increased intra-abdominal pressure, including obesity, chronic cough,
      constipation, and repeated heavy lifting, also contribute to prolapse. Most
      patients with pelvic organ prolapse are asymptomatic. Symptoms become more
      bothersome as the bulge protrudes past the vaginal opening. Initial evaluation
      includes a history and systematic pelvic examination including assessment for
      urinary incontinence, bladder outlet obstruction, and fecal incontinence.
      Treatment options include observation, vaginal pessaries, and surgery. Most women
      can be successfully fit with a vaginal pessary. Available surgical options are
      reconstructive pelvic surgery with or without mesh augmentation and obliterative
      surgery.

PMID- 28762695
TI  - Which Probiotics Should I Take? A Practical Guide for Family Physicians.

PMID- 28762696
TI  - Probiotics for Gastrointestinal Conditions: A Summary of the Evidence.
AB  - Probiotics contain microorganisms, most of which are bacteria similar to the
      beneficial bacteria that occur naturally in the human gut. Probiotics have been
      widely studied in a variety of gastrointestinal diseases. The most-studied
      species include Lactobacillus, Bifidobacterium, and Saccharomyces. However, a
      lack of clear guidelines on when to use probiotics and the most effective
      probiotic for different gastrointestinal conditions may be confusing for family
      physicians and their patients. Probiotics have an important role in the
      maintenance of immunologic equilibrium in the gastrointestinal tract through the
      direct interaction with immune cells. Probiotic effectiveness can be species-,
      dose-, and disease-specific, and the duration of therapy depends on the clinical
      indication. There is high-quality evidence that probiotics are effective for
      acute infectious diarrhea, antibiotic-associated diarrhea, Clostridium difficile-
      associated diarrhea, hepatic encephalopathy, ulcerative colitis, irritable bowel
      syndrome, functional gastrointestinal disorders, and necrotizing enterocolitis.
      Conversely, there is evidence that probiotics are not effective for acute
      pancreatitis and Crohn disease. Probiotics are safe for infants, children,
      adults, and older patients, but caution is advised in immunologically vulnerable
      populations.

PMID- 28762697
TI  - Effects of Yoga in Patients with Asthma.

PMID- 28762698
TI  - Common Side Effects of HIV Medicines.

PMID- 28762699
TI  - Pelvic Organ Prolapse.

PMID- 28762700
TI  - What are Probiotics?

PMID- 28762701
TI  - Epilepsy: Treatment Options.
AB  - The occurrence of a single seizure does not always require initiation of
      antiepileptic drugs. Risk of recurrent seizures should guide their use. In
      adults, key risk factors for recurrence are two unprovoked seizures occurring
      more than 24 hours apart, epileptiform abnormalities on electroencephalography,
      abnormal brain imaging, nocturnal seizures, or an epileptic syndrome associated
      with seizures. In children, key risk factors are abnormal electroencephalography
      results, an epileptic syndrome associated with seizures, severe head trauma, and
      cerebral palsy. The risk of adverse effects from antiepileptic drugs is
      considerable and includes potential cognitive and behavioral effects. In the
      absence of risk factors, and because many patients do not experience recurrence
      of a seizure, physicians should consider delaying use of antiepileptic drugs
      until a second seizure occurs. Delaying therapy until a second seizure does not
      affect one- to two-year remission rates. Treatment should begin with monotherapy.
      The appropriate choice of medication varies depending on seizure type. Routine
      monitoring of drug levels is not correlated with reduction in adverse effects or
      improvement in effectiveness and is not recommended. When patients have been
      seizure free for two to five years, discontinuation of antiepileptic drugs may be
      considered. For patients with seizures that are not controlled with these agents,
      alternative treatments include surgical resection of the seizure focus, ketogenic
      diets, vagus nerve stimulators, and implantable brain neurostimulators. Patients
      who have had a recent seizure within the past three months or whose seizures are
      poorly controlled should refrain from driving and certain high-risk physical
      activities. Patients planning for pregnancy should know that antiepileptic drugs
      are possibly teratogenic.

PMID- 28762702
TI  - High False-Positive Rate with Lung Cancer Screening.

PMID- 28762704
TI  - Niacin Does Not Decrease Mortality in Patients with Coronary Artery Disease or
      Low HDL.

PMID- 28762705
TI  - Peanut Allergy Prevention: Guidelines from the NIAID.

PMID- 28762706
TI  - Hypoxemia and Nonproductive Cough.

PMID- 28762707
TI  - Primary Care for Refugees: Challenges and Opportunities.
AB  - Since 1975, more than 3 million refugees have settled in the United States,
      fleeing unrest, conflict, and persecution. Refugees represent diverse ethnic,
      cultural, religious, socioeconomic, and educational backgrounds. Despite this
      heterogeneity, there are commonalities in the refugee experience. Before
      resettlement, all refugees must undergo an overseas medical screening to detect
      conditions that pose a potential health threat in the United States. On arrival,
      they should undergo an examination to detect diseases with high prevalence in
      their country of origin or departure. Refugees have higher rates of chronic pain
      compared with the general population, and their mental health and wellbeing are
      strongly influenced by their migration history. Refugees have higher rates of
      mood disorders, posttraumatic stress disorder, and anxiety than the general
      population. Some refugees have been tortured, which contributes to poorer health.
      Chronic noncommunicable diseases, such as diabetes mellitus and hypertension, are
      also prevalent among refugees. Many refugees may be missing routine immunizations
      and screenings for cancer and chronic diseases. Attention to reproductive health,
      oral health, and vision care will help identify and address previously unmet
      needs. Refugees face barriers to care as a result of cultural, language, and
      socioeconomic factors.

PMID- 28762708
TI  - Refugee Mental Health: A Primary Care Approach.

PMID- 28762709
TI  - Treatment for Calcaneal Apophysitis.

PMID- 28762710
TI  - Screening for Obstructive Sleep Apnea in Adults.

PMID- 28762711
TI  - Screening for Obstructive Sleep Apnea in Adults: Recommendation Statement.

PMID- 28762713
TI  - Greater Benefit with Rivaroxaban Than Aspirin for Extended Treatment of VTE.

PMID- 28762712
TI  - Common Herbal Dietary Supplement-Drug Interactions.
AB  - Nearly 25% of U.S. adults report concurrently taking a prescription medication
      with a dietary supplement. Some supplements, such as St. John's wort and
      goldenseal, are known to cause clinically important drug interactions and should
      be avoided by most patients receiving any pharmacologic therapy. However, many
      other supplements are predicted to cause interactions based only on in vitro
      studies that have not been confirmed or have been refuted in human clinical
      trials. Some supplements may cause interactions with a few medications but are
      likely to be safe with other medications (e.g., curcumin, echinacea, garlic,
      Asian ginseng, green tea extract, kava kava). Some supplements have a low
      likelihood of drug interactions and, with certain caveats, can safely be taken
      with most medications (e.g., black cohosh, cranberry, ginkgo, milk thistle,
      American ginseng, saw palmetto, valerian). Clinicians should consult reliable
      dietary supplement resources, or clinical pharmacists or pharmacologists, to help
      assess the safety of specific herbal supplement-drug combinations. Because most
      patients do not disclose supplement use to clinicians, the most important
      strategy for detecting herb-drug interactions is to develop a trusting
      relationship that encourages patients to discuss their dietary supplement use.

PMID- 28762714
TI  - What Should I Know About Seizures and Epilepsy?

PMID- 28762715
TI  - Understanding Interfacial Alignment in Solution Coated Conjugated Polymer Thin
      Films.
AB  - Domain alignment in conjugated polymer thin films can significantly enhance
      charge carrier mobility. However, the alignment mechanism during meniscus-guided
      solution coating remains unclear. Furthermore, interfacial alignment has been
      rarely studied despite its direct relevance and critical importance to charge
      transport. In this study, we uncover a significantly higher degree of alignment
      at the top interface of solution coated thin films, using a donor-acceptor
      conjugated polymer, poly(diketopyrrolopyrrole-co-thiophene-co-thieno[3,2
      b]thiophene-co-thiophene) (DPP2T-TT), as the model system. At the molecular
      level, we observe in-plane pi-pi stacking anisotropy of up to 4.8 near the top
      interface with the polymer backbone aligned parallel to the coating direction.
      The bulk of the film is only weakly aligned with the backbone oriented transverse
      to coating. At the mesoscale, we observe a well-defined fibril-like morphology at
      the top interface with the fibril long axis pointing toward the coating
      direction. Significantly smaller fibrils with poor orientational order are found
      on the bottom interface, weakly aligned orthogonal to the fibrils on the top
      interface. The high degree of alignment at the top interface leads to a charge
      transport anisotropy of up to 5.4 compared to an anisotropy close to 1 on the
      bottom interface. We attribute the formation of distinct interfacial morphology
      to the skin-layer formation associated with high Peclet number, which promotes
      crystallization on the top interface while suppressing it in the bulk. We further
      infer that the interfacial fibril alignment is driven by the extensional flow on
      the top interface arisen from increasing solvent evaporation rate closer to the
      meniscus front.

PMID- 28762716
TI  - Review of Electrochemically Triggered Macromolecular Film Buildup Processes and
      Their Biomedical Applications.
AB  - Macromolecular coatings play an important role in many technological areas,
      ranging from the car industry to biosensors. Among the different coating
      technologies, electrochemically triggered processes are extremely powerful
      because they allow in particular spatial confinement of the film buildup up to
      the micrometer scale on microelectrodes. Here, we review the latest advances in
      the field of electrochemically triggered macromolecular film buildup processes
      performed in aqueous solutions. All these processes will be discussed and related
      to their several applications such as corrosion prevention, biosensors,
      antimicrobial coatings, drug-release, barrier properties and cell encapsulation.
      Special emphasis will be put on applications in the rapidly growing field of
      biosensors. Using polymers or proteins, the electrochemical buildup of the films
      can result from a local change of macromolecules solubility, self-assembly of
      polyelectrolytes through electrostatic/ionic interactions or covalent cross
      linking between different macromolecules. The assembly process can be in one step
      or performed step-by-step based on an electrical trigger affecting directly the
      interacting macromolecules or generating ionic species.

PMID- 28762717
TI  - Toward Efficient and Metal-Free Emissive Devices: A Solution-Processed Host-Guest
      Light-Emitting Electrochemical Cell Featuring Thermally Activated Delayed
      Fluorescence.
AB  - The next generation of emissive devices should preferably be efficient, low-cost,
      and environmentally sustainable, and as such utilize all electrically generated
      excitons (both singlets and triplets) for the light emission, while being free
      from rare metals such as iridium. Here, we report on a step toward this vision
      through the design, fabrication, and operation of a host-guest light-emitting
      electrochemical cell (LEC) featuring an organic thermally activated delayed
      fluorescence (TADF) guest that harvests both singlet and triplet excitons for the
      emission. The rare-metal-free active material also consists of a polymeric
      electrolyte and a polymeric compatibilizer for the facilitation of a cost
      efficient and scalable solution-based fabrication, and for the use of air-stable
      electrodes. We report that such TADF-LEC devices can deliver uniform green light
      emission with a maximum luminance of 228 cd m-2 when driven by a constant-current
      density of 770 A m-2, and 760 cd m-2 during a voltage ramp, which represents a
      one-order-of-magnitude improvement in comparison to previous TADF-emitting LECs.

PMID- 28762718
TI  - 3D Printing Polymers with Supramolecular Functionality for Biological
      Applications.
AB  - Supramolecular chemistry continues to experience widespread growth, as fine-tuned
      chemical structures lead to well-defined bulk materials. Previous literature
      described the roles of hydrogen bonding, ionic aggregation, guest/host
      interactions, and pi-pi stacking to tune mechanical, viscoelastic, and processing
      performance. The versatility of reversible interactions enables the more facile
      manufacturing of molded parts with tailored hierarchical structures such as
      tissue engineered scaffolds for biological applications. Recently, supramolecular
      polymers and additive manufacturing processes merged to provide parts with
      control of the molecular, macromolecular, and feature length scales. Additive
      manufacturing, or 3D printing, generates customizable constructs desirable for
      many applications, and the introduction of supramolecular interactions will
      potentially increase production speed, offer a tunable surface structure for
      controlling cell/scaffold interactions, and impart desired mechanical properties
      through reinforcing interlayer adhesion and introducing gradients or self
      assembled structures. This review details the synthesis and characterization of
      supramolecular polymers suitable for additive manufacture and biomedical
      applications as well as the use of supramolecular polymers in additive
      manufacturing for drug delivery and complex tissue scaffold formation. The effect
      of supramolecular assembly and its dynamic behavior offers potential for
      controlling the anisotropy of the printed objects with exquisite geometrical
      control. The potential for supramolecular polymers to generate well-defined
      parts, hierarchical structures, and scaffolds with gradient properties/tuned
      surfaces provides an avenue for developing next-generation biomedical devices and
      tissue scaffolds.

PMID- 28762719
TI  - Octagonal Wetting Interface Evolution of Evaporating Saline Droplets on a
      Micropyramid Patterned Surface.
AB  - Textured surfaces have been extensively employed to investigate the dynamics,
      wetting phenomena, and shape of liquid droplets. Droplet shape can be controlled
      via the manipulation of topographic or chemical heterogeneity of a solid surface
      by anchoring the three-phase line at specific sites. In this study, we
      demonstrate that droplet shape on a topographically patterned surface can be
      modified by varying the concentration of salt potassium chloride (KCl) in the
      droplet solution. It is found that at the beginning of evaporation the octagonal
      shape of the solid-liquid interface is changed to a rectangle with corners cut
      upon increasing the salt concentration. Such a variation in the solid-liquid
      interface versus the salt concentration is explained by the analysis of free
      energy difference. It indicates that the increases in solid-liquid and liquid
      vapor surface tensions by raising the salt concentration result in a favored
      extension of the three-phase line intersecting the micropyramid bottom sides than
      the counterpart intersecting the micropyramid diagonal edges. The saline droplets
      experience a pinning stage at first and a depinning one afterward. The onset of
      depinning is delayed, and at which the instantaneous contact angle is larger upon
      raising the salt concentration. The three-phase line which intersects the
      micropyramid diagonal edges recedes ahead of the one along the micropyramid
      bottom sides, making the octagonal wetting interface evolve toward a circle. A
      close view at the droplet edge indicates that the three-phase line repeats "slow
      slip-rapid slip" across row by row of micropyramids during the depinning stage.

PMID- 28762720
TI  - Rationally Incorporated MoS2/SnS2 Nanoparticles on Graphene Sheets for Lithium
      Ion and Sodium-Ion Batteries.
AB  - Herein, we have designed and first synthesized a unique ternary hybrid structure
      by simultaneously growing SnS2 and MoS2 particles on graphene sheets (denoted as
      MoS2/SnS2-GS) via one-pot hydrothermal route. The charge incompatibility between
      MoO42- and graphene oxide with negative charged functional groups on surface can
      be compromised with the aid of Sn4+ cations, which renders the final formation of
      SnS2 and MoS2 on GS surface. This is the first report of the cohybridization of
      MoS2 and SnS2 with GS matrix from anionic and cationic precursors in the absence
      of premedication of graphene surface. When MoS2/SnS2-GS acts as anodes for
      lithium-ion batteries, the hybrids exhibit much better cycling stability than
      MoS2-GS and SnS2-GS counterparts. The compact adhesion of MoS2/SnS2 nanoparticles
      helps offset the undesired result of destruction of electrode materials resulting
      from volume expansion during repeated cycles. Furthermore, by combination with
      their synergetic effect on interface and the presence of discrepant asynchronous
      electrochemical reactions for SnS2 and MoS2, MoS2/SnS2-GS hybrids are endowed
      with improvement of electrochemical capabilities. Besides, they also showed
      outstanding Na-storage ability.

PMID- 28762721
TI  - Supramolecular Corrals on Surfaces Resulting from Aromatic Interactions of
      Nonplanar Triazoles.
AB  - Interaction forces between aromatic moieties, often referred to as pi-pi
      interactions, are an important element in stabilizing complex supramolecular
      structures. For supramolecular self-assembly occurring on surfaces, where
      aromatic moieties are typically forced to adsorb coplanar with the surface, the
      possible role of intermolecular aromatic interactions is much less explored.
      Here, we report on unusual, ring-shaped supramolecular corral surface structures
      resulting from adsorption of a molecule with nonplanar structure, allowing for
      intermolecular aromatic interactions. The discrete corral structures are observed
      using high-resolution scanning tunneling microscopy, and the energetic driving
      forces for their formation are elucidated using density functional theory
      calculations and Monte Carlo simulations. The individual corrals involve between
      11 and 18 molecules bound through triazole moieties to a ring-shaped ensemble of
      bridge site positions on (111) surfaces of copper, silver, or gold. The curvature
      required to form the corrals is identified to result from the angle dependence of
      aromatic interactions between molecular phenanthrene moieties. The study provides
      detailed quantitative insights into triazole-surface and aromatic interactions
      and illustrates how they may be used to drive surface supramolecular self
      assembly.

PMID- 28762722
TI  - Posttranslational Modification of Heme b in a Bacterial Peroxidase: The Role of
      Heme to Protein Ester Bonds in Ligand Binding and Catalysis.
AB  - The existence of covalent heme to protein bonds is the most striking structural
      feature of mammalian peroxidases, including myeloperoxidase and lactoperoxidase
      (LPO). These autocatalytic posttranslational modifications (PTMs) were shown to
      strongly influence the biophysical and biochemical properties of these
      oxidoreductases. Recently, we reported the occurrence of stable LPO-like
      counterparts with two heme to protein ester linkages in bacteria. This study
      focuses on the model wild-type peroxidase from the cyanobacterium Lyngbya sp. PCC
      8106 (LspPOX) and the mutants D109A, E238A, and D109A/E238A that could be
      recombinantly produced as apoproteins in Escherichia coli, fully reconstituted to
      the respective heme b proteins, and posttranslationally modified by hydrogen
      peroxide. This for the first time allows not only a direct comparison of the
      catalytic properties of the heme b and PTM forms but also a study of the impact
      of D109 and E238 on PTM and catalysis, including Compound I formation and the two
      electron reduction of Compound I by bromide, iodide, and thiocyanate. It is
      demonstrated that both heme to protein ester bonds can form independently and
      that elimination of E238, in contrast to exchange of D109, does not cause
      significant structural rearrangements or changes in the catalytic properties
      neither in heme b nor in the PTM form. The obtained findings are discussed with
      respect to published structural and functional data of human peroxidases.

PMID- 28762724
TI  - Transparent Bipolar Membrane for Water Splitting Applications.
AB  - This study describes the use of a benzimidazolium-based anion exchange membrane
      for creating bipolar membranes and the assessment of their suitability for solar
      driven water splitting. Bipolar membranes were prepared by laminating anion
      exchange membrane with Nafion NR-211 membrane without modification of the
      interface. Under acidic and basic conditions, proton and hydroxide ion
      conductivities of 103 and 102 mS cm-1 were obtained for Nafion and
      benzimidazolium-based membranes, respectively. The fabricated bipolar membranes
      have an average thickness of 90 MUm and show high transmittance, up to 75% of the
      visible light. The findings suggest that the two membranes create a sharp
      hydrophilic interface with a space charge region of only a few nanometers,
      thereby generating a large electric field at the interface that enhances water
      dissociation.

PMID- 28762725
TI  - Methane and CO2 Adsorption Capacities of Kerogen in the Eagle Ford Shale from
      Molecular Simulation.
AB  - Over the past decade, the United States has become a world leader in natural gas
      production, thanks in part to a large-fold increase in recovery from
      unconventional resources, i.e., shale rock and tight oil reservoirs. In an
      attempt to help mitigate climate change, these depleted formations are being
      considered for their long-term CO2 storage potential. Because of the variability
      in mineral and structural composition from one formation to the next (even within
      the same region), it is imperative to understand the adsorption behavior of CH4
      and CO2 in the context of specific conditions and pore surface chemistry, i.e.,
      relative total organic content (TOC), clay, and surface functionality. This study
      examines two Eagle Ford shale samples, both recovered from shale that was
      extracted at depths of approximately 3800 m and having low clay content (i.e.,
      less than 5%) and similar mineral compositions but distinct TOCs (i.e., 2% and
      5%, respectively). Experimentally validated models of kerogen were used to the
      estimate CH4 and CO2 adsorption capacities. The pore size distributions modeled
      were derived from low-pressure adsorption isotherm data using CO2 and N2 as probe
      gases for micropores and mesopores, respectively. Given the presence of water in
      these natural systems, the role of surface chemistry on modeled kerogen pore
      surfaces was investigated. Several functional groups associated with surface
      dissociated water were considered. Pressure conditions from 10 to 50 bar were
      investigated using grand canonical Monte Carlo simulations along with typical
      outgassing temperatures used in many shale characterization and adsorption
      studies (i.e., 60 and 250  degrees C). Both CO2 and N2 were used as probe gases
      to determine the total pore volume available for gas adsorption spanning pore
      diameters ranging from 0.3 to 30 nm. The impacts of surface chemistry, outgassing
      temperature, and the inclusion of nanopores with diameters of less than 1.5 nm
      were determined for applications of CH4 and CO2 storage from samples of the gas
      producing region of the Eagle Ford Shale. At 50 bar and temperatures of 60 and
      250  degrees C, CH4 adsorption increased across all surface chemistries
      considered by 60% and 2-fold, respectively. In the case of CO2, the surface
      chemistry played a role at both 10 and 50 bar. For instance, at temperatures of
      60 and 250  degrees C, CO2 adsorption increased across all surface chemistries by
      6-fold and just over 2-fold, respectively. It was also found that at both 10 and
      50 bar, if too low an outgassing temperature is used, this may lead to a 2-fold
      underestimation of gas in place. Finally, neglecting to include pores with
      diameters of less than 1.5 nm has the potential to underestimate pore volume by
      up to 28%. Taking into consideration these aspects of kerogen and shale
      characterization in general will lead to improvements in estimating the CH4 and
      CO2 storage potential of gas shales.

PMID- 28762723
TI  - Single-Molecule Plasmon Sensing: Current Status and Future Prospects.
AB  - Single-molecule detection has long relied on fluorescent labeling with high
      quantum-yield fluorophores. Plasmon-enhanced detection circumvents the need for
      labeling by allowing direct optical detection of weakly emitting and completely
      nonfluorescent species. This review focuses on recent advances in single molecule
      detection using plasmonic metal nanostructures as a sensing platform,
      particularly using a single particle-single molecule approach. In the past decade
      two mechanisms for plasmon-enhanced single-molecule detection have been
      demonstrated: (1) by plasmonically enhancing the emission of weakly fluorescent
      biomolecules, or (2) by monitoring shifts of the plasmon resonance induced by
      single-molecule interactions. We begin with a motivation regarding the importance
      of single molecule detection, and advantages plasmonic detection offers. We
      describe both detection mechanisms and discuss challenges and potential
      solutions. We finalize by highlighting the exciting possibilities in analytical
      chemistry and medical diagnostics.

PMID- 28762727
TI  - Assembly of Multifunctional Ni2P/NiS0.66 Heterostructures and Their
      Superstructure for High Lithium and Sodium Anodic Performance.
AB  - The combination of structure designs at the microscopic and macroscopic level can
      efficiently enable electrode materials with greatly enhanced lithium and sodium
      storage. In this paper, the construction of Ni2P/NiS0.66 heterostructures and
      their assembly into a superstructure at the nanoscale were successfully achieved
      by a facile and effective strategy. In the obtained superstructure, the
      Ni2P/NiS0.66 heterostructures are homogeneously coated with ultrathin carbon
      layers (HT-NPS@C) and, at the same time, assembled into a yolk-shell nanosphere.
      Upon evaluation as the anode materials for Li-ion batteries, the HT-NPS@C
      delivers a high reversible capacity of 430 mA h g-1 after 200 cycles at 200 mA g
      1 and ultrastable cyclability with negligible capacity loss over 500 cycles.
      Furthermore, the coin-type full cell with the LiNi1/3Co1/3Mn1/3O2 (LNCMO) cathode
      and HT-NPS@C anode deliver a high specific capacity of 323.5 mA h g-1 after 50
      cycles at 0.3 A g-1. Apart from an excellent performance as promising anode
      materials for LIBs (Li-ion batteries), the Na-ion batteries with HT-NPS@C sphere
      electrodes also manifest a remarkable electrochemical performance.

PMID- 28762726
TI  - Intracellular Uncaging of cGMP with Blue Light.
AB  - We have made a new caged cGMP that is photolyzed with blue light. Using our
      recently developed derivative of 7-diethylaminocourmarin (DEAC) called DEAC450,
      we synthesized coumarin phosphoester derivatives of cGMP with two negative
      charges appended to the DEAC450 moiety. DEAC450-cGMP is freely soluble in
      physiological buffer without the need for any organic cosolvents. With a
      photolysis quantum yield of 0.18 and an extinction coefficient of 43 000 M-1 cm-1
      at 453 nm, DEAC450-cGMP is the most photosensitive caged cGMP made to date. In
      patch-clamped neurons in acutely isolated brain slices, blue light effectively
      uncaged cGMP from DEAC450 and facilitated activation of hyperpolarization and
      cyclic nucleotide gated cation (HCN) channels in cholinergic interneurons. Thus,
      DEAC450-cGMP has a unique set of optical and chemical properties that make it a
      useful addition to the optical arsenal available to neurobiologists.

PMID- 28762728
TI  - High Performing Ternary Solar Cells through Forster Resonance Energy Transfer
      between Nonfullerene Acceptors.
AB  - Nonradiative Forster resonance energy transfer (FRET) is an important mechanism
      of organic solar cells, which can improve the exciton migration over a long
      distance, resulting in improvement of efficiency of solar cells. However, the
      current observations of FRET are very limited, and the efficiencies are less than
      9%. In this study, FRET effect was first observed between two nonfullerene
      acceptors in ternary solar cells, which improved both the absorption range and
      exciton harvesting, leading to the dramatic enhancement in the short circuit
      current and power conversion efficiency. Moreover, this strategy is proved to be
      a versatile platform for conjugated polymers with different bandgaps, resulting
      in a remarkable efficiency of 10.4%. These results demonstrated a novel method to
      enhance the efficiency of organic soar cells.

PMID- 28762729
TI  - Activation and Loading of the Starter Unit during Thiocoraline Biosynthesis.
AB  - The initiation of the nonribosomal peptide synthetase (NRPS) assembly of the
      bisintercalator natural product thiocoraline involves key enzymatic steps for AMP
      activation and carrier protein loading of the starter unit 3-hydroxyquinaldic
      acid (3HQA). Gene cluster data combined with protein sequence homology analysis
      originally led us to propose that TioJ could be responsible for the AMP
      activation step, whereas TioO could act as the thiolation (T) domain,
      facilitating the transfer of 3HQA to the next NRPS module, TioR. Herein, we
      confirmed the involvement of TioJ in thiocoraline biosynthesis by tioJ knockout
      and in vitro activation of 3HQA studies. However, we demonstrated that TioJ
      activated 3HQA is not loaded onto the T domain TioO, as originally believed, but
      instead onto a fatty acid synthase (FAS) acyl carrier protein (ACP) domain FabC,
      which is located outside of the thiocoraline gene cluster. We showed a strong
      interaction between TioJ and FabC. By generating TioJ point mutants mimicking the
      active site of highly homologous enzymes activating different molecules, we
      showed that the identity of the substrate activated by adenylation domains such
      as TioJ is not determined by only the active site residues that directly interact
      with the substrate. The insights gained from these enzymatic transformations are
      valuable in the efforts toward deciphering the complete biosynthetic pathway of
      thiocoraline and bisintercalators in general.

PMID- 28762731
TI  - New Synthetic Approach to Molecular Rods Using Cyclophosphazene-Based
      Oligospiranes.
AB  - A synthetic approach was developed to prepare a new type of highly functionalized
      inorganic-organic heterocyclic molecular rod (3a and 3b) consisting of
      cyclophosphazene and carbocyclic units. Single-crystal X-ray diffraction analysis
      of 3a revealed that the molecular length was ca. 2.5 nm. The products of this
      high-yield process have the potential for derivatization via known phosphazene
      reactions.

PMID- 28762730
TI  - Dual Quantification of MicroRNAs and Telomerase in Living Cells.
AB  - The development of a unique and universal strategy for the simultaneous
      quantification of different types of biomolecules (i.e., nucleic acids and
      proteins) in living cells is extremely challenging. Herein, a two-signal
      platform, based upon surface-enhanced Raman scattering and upconversion, for the
      ultrasensitive and quantitative in situ detection of microRNA (miR)-21 and
      telomerase in living cells is reported. In the presence of miR-21 and telomerase,
      the hybridization of miR-21 with a molecular beacon leads to the separation of
      3,3'-diethylthiocarbamyl cyanine iodide-modified Au NR dimers, resulting in a
      decrease in Raman signal. Also, the target telomerase triggers elongation of the
      telomerase primer strands, followed by substitutional hybridization and release
      of upconversion nanoparticles, leading to an increase in luminescence. A linear
      relationship between the Raman intensities and logarithmic concentration of
      intracellular miR-21 between 0.021 and 22.36 amol/ngRNA is observed, and the
      limit of detection (LOD) was determined to be 0.011 amol/ngRNA. The luminescence
      data show a linear response between 0.6 * 10-12 and 31 * 10-12 IU for logarithmic
      concentration of intracellular telomerase with a LOD of 3.2 * 10-13 IU. These
      results are in good agreement with Raman and confocal imaging. Importantly, the
      ultrasensitive detection of miR-21 was possible due to strong plasmonic "hot
      spots". This innovative two-signal approach can be utilized for the quantitative
      and precise detection of many types of signaling molecules in living cells and to
      understand the chemistry within cellular systems and its application in the
      diagnosis of disease.

PMID- 28762732
TI  - Plasmonic ELISA Based on Nanospherical Brush-Induced Signal Amplification for the
      Ultrasensitive Naked-Eye Simultaneous Detection of the Typical
      Tetrabromobisphenol A Derivative and Byproduct.
AB  - On the basis of H2O2-mediated growth of gold nanoparticle (AuNPs), a novel
      plasmonic enzyme-linked immunosorbent assay (pELISA) was developed with a
      polyclonal antibody for the ultrasensitive simultaneous naked-eye detection of
      tetrabromobisphenol A bis(2-hydroxyetyl) ether (TBBPA DHEE) and
      tetrabromobisphenol A mono(hydroxyethyl) ether (TBBPA MHEE), one of the major
      derivatives and byproducts of tetrabromobisphenol A (TBBPA), respectively. In
      this modified indirect competitive pELISA, glucose oxidase (GOx) played an
      important role leading to the growth of AuNPs through a reaction between GOx and
      glucose to produce hydrogen peroxide (H2O2). In addition, further signal
      amplification was achieved via a large number of GOx molecules, which were
      immobilized on silica nanoparticles carrying poly brushes (SiO2@PAA) to increase
      the enzyme load, and the whole complex was conjugated on the second antibody.
      Under the optimized conditions, 10-3 MUg/L TBBPA DHEE can be distinguished via
      the observation of a colored solution, and the limit of detection (LOD) of the
      method using a microplate reader reaches 3.3 * 10-4 MUg/L. In contrast, the
      sensitivity of the method was 3 orders of magnitude higher than that using
      conventional colorimetric ELISA with the same antibody. Furthermore, the proposed
      approach showed good repeatability and reliability after a recovery test
      fortified with a variety of targets was performed (recoveries, 78.00-102.79%;
      coefficient of variation (CV), 4.38-9.87%). To our knowledge, this is the first
      case in which pELISA was applied for the detection of small molecules via the
      production of H2O2 from GOx and glucose. The method will be widely used for the
      investigation of TBBPA DHEE and TBBPA MHEE in real environments.

PMID- 28762733
TI  - Chern Insulator and Chern Half-Metal States in the Two-Dimensional Spin-Gapless
      Semiconductor Mn2C6S12.
AB  - Two-dimensional metal-organic frameworks (2D-MOFs) with exotic electronic
      structures are drawing increasing attention. Here, using first-principles
      calculations, we demonstrate a spin-gapless MOF, namely, Mn2C6S12, with the
      coexistence of a spin-polarized Dirac cone and parabolic degenerate points. The
      Curie temperature evaluated from Monte Carlo simulations implies Mn2C6S12
      possessing stable ferromagnetism at room temperature. Taking the spin-orbit
      coupling into account, the Dirac cone is gapped and the degenerate points are
      lifted, giving rise to multiple topologically nontrivial states with nonzero
      Chern number, which imply the possibility of Mn2C6S12 to be a Chern insulator and
      a Chern half-metal. Our results offer versatile platforms for achieving spin
      filtering or a quantum anomalous Hall effect with promising application in
      spintronics devices.

PMID- 28762734
TI  - Interfacial Electron Injection Probed by a Substrate-Specific Excitonic
      Signature.
AB  - Ultrafast interfacial electron transfer in sensitized solar cells has mostly been
      probed by visible-to-terahertz radiation, which is sensitive to the free carriers
      in the conduction band of the semiconductor substrate. Here, we demonstrate the
      use of deep-ultraviolet continuum pulses to probe the interfacial electron
      transfer, by detecting a specific excitonic transition in both N719-sensitized
      anatase TiO2 and wurtzite ZnO nanoparticles. Our results are compared to those
      obtained on bare nanoparticles upon above-gap excitation. We show that the signal
      upon electron injection from the N719 dye into TiO2 is dominated by long-range
      Coulomb screening of the final states of the excitonic transitions, whereas in
      sensitized ZnO it is dominated by phase-space filling. The present approach
      offers a possible route to detecting interfacial electron transfer in a broad
      class of systems, including other transition metal oxides or sensitizers.

PMID- 28762735
TI  - In Situ Generation of Quinolinium Ylides from Diazo Compounds: Copper-Catalyzed
      Synthesis of Indolizine.
AB  - The Cu-catalyzed three-component reaction between quinolines, diazo compounds,
      and alkenes has been established for direct construction of indolizine
      derivatives via quinolinium ylides. This methodology is distinguished by the use
      of a commercially inexpensive catalyst and readily available starting materials,
      wide substrate scope, and operational simplicity.

PMID- 28762736
TI  - High-Resolution Solid-State NMR Characterization of Ligand Binding to a Protein
      Immobilized in a Silica Matrix.
AB  - Solid-state NMR is becoming a powerful tool to detect atomic-level structural
      features of biomolecules even when they are bound to (or trapped in) solid
      systems that lack long-range three-dimensional order. We here demonstrate that it
      is possible to probe protein-ligand interactions from a protein-based perspective
      also when the protein is entrapped in silica, thus translating into biomolecular
      solid-state NMR all of the considerations that are usually made to understand the
      chemical nature of the interaction of a protein with its ligands. This work
      provides a proof of concept that also immobilized enzymes can be used for protein
      based NMR protein-ligand interactions for drug discovery.

PMID- 28762737
TI  - MNgCCH (M = Cu, Ag, Au; Ng = Xe, Rn): The First Set of Compounds with M-Ng-C
      Bonding Motif.
AB  - Although Ng-M (M = Cu, Ag, Au; Ng = noble gas) and Ng-C bonds are known to exist
      in different viable species, we report here a series of systems with formula
      MNgCCH (Ng = Xe, Rn) in which both bonds coexist. These compounds possess
      reasonably high kinetic stability (free energy barrier, DeltaG? of 14.0-34.8
      kcal/mol) along an exergonic isomerization channel, MNgCCH -> NgMCCH. For a given
      M, the DeltaG? associated with this channel increases from Xe to Rn, whereas for
      a given Ng, it increases along Ag < Cu < Au. No other possible dissociation
      channel is feasible at standard condition, except for the Ag-Xe analogue, where
      one three-body neutral dissociation channel, AgXeCCH -> Ag + Xe + CCH, is
      slightly exergonic by 2.4 kcal/mol. Examination of the thermochemical stability
      of the Ng-M bonds in noninserted compounds against the dissociation, NgMCCH -> Ng
      + MCCH reveals that Kr-Rn bound Cu and Au analogues, and Xe and Rn bound Ag
      analogues would be viable at 298 K. The natural bond order analysis indicates the
      formation of M-Ng covalent bond and Ng-C ionic bonds in these compounds having an
      ionic representation of (MNg)+(CCH)-. Energy decomposition analysis reveals a
      significant contribution of the electrostatic term in the M-Ng covalent bonds.

PMID- 28762738
TI  - Enzyme-Mediated Directional Transport of a Small-Molecule Walker With Chemically
      Identical Feet.
AB  - We describe a small-molecule "walker" that uses enzyme catalysis to discriminate
      between the relative positions of its "feet" on a track and thereby move with net
      directionality. The bipedal walker has identical carboxylic acid feet, and
      "steps" along an isotactic hydroxyl-group-derivatized polyether track by the
      formation/breakage of ester linkages. Lipase AS catalyzes the selective
      hydrolysis of the rear foot of macrocyclized walkers (an information ratchet
      mechanism), the rear foot producing an (R)-stereocenter at its point of
      attachment to the track. If the hydrolyzed foot reattaches to the track in front
      of the bound foot it forms an (S)-stereocenter, which is resistant to enzymatic
      hydrolysis. Only macrocyclic walker-track conjugates are efficiently hydrolyzed
      by the enzyme, leading to high processivity of the walker movement along the
      track. Conventional chemical reagents promote formation of the ester bonds
      between the walker and the track. Iterative macrocyclization and hydrolysis
      reactions lead to 68% of walkers taking two steps directionally along a three
      foothold track.

PMID- 28762739
TI  - Ultrafast Spectroscopic Dynamics of Quinacrine-Riboflavin Binding Protein
      Interactions.
AB  - Redox active cofactors play a dynamic role inside protein binding active sites
      because the amino acids responsible for binding participate in electron transfer
      (ET) reactions. Here, we use femtosecond transient absorption (FsTA) spectroscopy
      to examine the ultrafast ET between quinacrine (Qc), an antimalarial drug with
      potential anticancer activity, and riboflavin binding protein (RfBP) with a known
      Kd = 264 nM. Steady-state absorption reveals a ~ 10 nm red-shift in the ground
      state when QcH32+ is titrated with RfBP, and a Stern-Volmer analysis shows ~84%
      quenching and a blue-shift of the QcH32+ photoluminescence to form a 1:1 binding
      ratio of the QcH32+-RfBP complex. Upon selective photoexcitation of QcH32+ in the
      QcH32+-RfBP complex, we observe charge separation in 7 ps to form 1[QcH3_red*+
      RfBP*+], which persists for 138 ps. The FsTA spectra show the spectroscopic
      identification of QcH3_red*+, determined from spectroelectrochemical measurements
      in DMSO. We correlate our results to literature and report lifetimes that are 10
      20* slower than the natural riboflavin, Rf-RfBP, complex and are oxygen
      independent. Driving force (DeltaG) calculations, corrected for estimated
      dielectric constants for protein hydrophobic pockets, and Marcus theory depict a
      favorable one-electron ET process between QcH32+ and nearby redox active tyrosine
      (Tyr) or tryptophan (Trp) residues.

PMID- 28762741
TI  - Suppressive Effect of Ginsenoside Rg3 against Lipopolysaccharide-Induced
      Depression-Like Behavior and Neuroinflammation in Mice.
AB  - Ginsenoside Rg3 (Rg3), a major active ingredient enriched in red ginseng,
      possesses well-confirmed immunoregulatory effects. Immune disturbance is a common
      trigger and aggravating factor of depression. The aim of this study was to
      explore the effects of Rg3 on lipopolysaccharide (LPS)-induced depression-like
      behavior in mice and the involvement of immune regulation. Pretreatment with Rg3
      (i.g., 20 and 40 mg/kg) effectively ameliorated LPS (i.p., 0.83 mg/kg) induced
      body weight loss, anorexia, and immobility time in both the tail suspension test
      and the forced swimming test. Rg3 attenuated the disturbed turnover of tryptophan
      and serotonin in the hippocampus, accompanied by decreased mRNA expression of pro
      inflammatory cytokines and indoleamine-2,3-dioxygenase (IDO). These central
      benefits were partially linked to the regulation of microglia activation and
      nuclear factor kappa B (NF-kappaB) pathway. In addition, Rg3 significantly
      reduced LPS-induced elevation of interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha) in plasma, and restored the systemic balance of tryptophan
      kynurenine metabolism. Taken together, our results demonstrated that Rg3 was
      effective in ameliorating depressive-like behavior induced by immune activation,
      adding new evidence to support its health benefits by immunoregulation.

PMID- 28762742
TI  - Probing Transient Release of Membrane-Sequestered Tyrosine-Based Signaling Motif
      by Solution NMR Spectroscopy.
AB  - Membrane sequestration of tyrosine-based signaling motifs of antigen receptors
      effectively restricts the signaling activities in resting lymphocytes. However,
      low level of basal signaling in resting cells is required for lymphocyte survival
      and antigen responsiveness, of which the molecular mechanism remains obscure.
      Here we probe the transient release of the cytoplasmic domain of the membrane
      bound IgG heavy chain (mIgG-tail) by hydrogen exchange NMR spectroscopy,
      illustrating a dynamic molecular basis for its basal signaling activity. To solve
      the severe resonance overlap problem in the 2D spectra of mIgG-tail, a non
      uniformly sampled pseudo-4D hydrogen exchange NMR experiment has been exploited
      to quantitatively measure site-specific hydrogen exchange rates. Our solution NMR
      study reveals transient solvent exposure of the ITT signaling motif that can be
      further enhanced by calcium ion, and provides insight into the mechanism of
      lymphocyte basal signaling.

PMID- 28762740
TI  - In Situ Characterization of Pharmaceutical Formulations by Dynamic Nuclear
      Polarization Enhanced MAS NMR.
AB  - A principal advantage of magic angle spinning (MAS) NMR spectroscopy lies in its
      ability to determine molecular structure in a noninvasive and quantitative
      manner. Accordingly, MAS should be widely applicable to studies of the structure
      of active pharmaceutical ingredients (API) and formulations. However, the low
      sensitivity encountered in spectroscopy of natural abundance APIs present at low
      concentration has limited the success of MAS experiments. Dynamic nuclear
      polarization (DNP) enhances NMR sensitivity and can be used to circumvent this
      problem provided that suitable paramagnetic polarizing agent can be incorporated
      into the system without altering the integrity of solid dosages. Here, we
      demonstrate that DNP polarizing agents can be added in situ during the
      preparation of amorphous solid dispersions (ASDs) via spray drying and hot-melt
      extrusion so that ASDs can be examined during drug development. Specifically, the
      dependence of DNP enhancement on sample composition, radical concentration,
      relaxation properties of the API and excipients, types of polarizing agents and
      proton density, has been thoroughly investigated. Optimal enhancement values are
      obtained from ASDs containing 1% w/w radical concentration. Both polarizing
      agents TOTAPOL and AMUPol provided reasonable enhancements. Partial deuteration
      of the excipient produced 3* higher enhancement values. With these parameters, an
      ASD containing posaconazole and vinyl acetate yields a 32-fold enhancement which
      presumably results in a reduction of NMR measurement time by ~1000. This boost in
      signal intensity enables the full assignment of the natural abundance
      pharmaceutical formulation through multidimensional correlation experiments.

PMID- 28762743
TI  - Fast Atom Beam- and Vacuum-Ultraviolet-Activated Sites for Low-Temperature Hybrid
      Integration.
AB  - The evolution of surface chemical structures of polyimide induced by Ar fast atom
      beam (Ar-FAB) bombardment and vacuum ultraviolet (VUV) irradiation was
      investigated using X-ray photoelectron spectroscopy (XPS) to clarify the
      activated sites for low-temperature hybrid bonding. These sites in molecular
      chains are considered corresponding to the bonding sites. They affect interfacial
      properties. Therefore, such analyses are necessary to optimize the processing
      parameters in different surface-modification methods. The XPS results
      demonstrated that Ar-FAB physical bombardment transformed the polyimide surface
      into benzene-dominant structures, whereas the effect of VUV irradiation was
      located at side chain groups such as ether and carbonyl, resulting in much longer
      molecular fragments (i.e., less matrix damage). Moreover, the calculated
      thickness of the VUV-induced modification layer grew to around 0.6 nm at its
      maximum.

PMID- 28762744
TI  - 2-Hydroxyindoline-3-triethylammonium Bromide: A Reagent for Formal C3
      Electrophilic Reactions of Indoles.
AB  - A novel indole-2,3-epoxide equivalent, 2-hydroxyindoline-3-triethylammonium
      bromide, was found to be a convenient reagent for formal C3-electrophilic
      reactions of indoles with various nucleophiles. By taking advantage of the
      nucleophilic character of the oxygen of the 2-hydroxyindoline, the interrupted
      retro-Claisen and interrupted Feist-Benary reactions with 1,3-dicarbonyl
      compounds were efficiently achieved.

PMID- 28762745
TI  - Total Synthesis and Stereochemical Revision of 4,8-Dihydroxy-3,4
      dihydrovernoniyne.
AB  - The first asymmetric total synthesis of two possible diastereomers (4S,5R)-4,8
      dihydroxy-3,4-dihydrovernoniyne 5 and (4S,5S)-4,8-dihydroxy-3,4-dihydrovernoniyne
      5a is accomplished. Salient features of the synthesis involve Cadiot-Chodkiewicz
      coupling and Sonogashira cross-coupling of terminal acetylenes. Detailed
      comparison of the 1H and 13C NMR data and specific rotation with that of the
      natural product led to the revision of the absolute stereochemistry of the
      natural product as (4S,5S)-4,8-dihydroxy-3,4-dihydrovernoniyne 5a.

PMID- 28762746
TI  - Xishacorenes A-C, Diterpenes with Bicyclo[3.3.1]nonane Nucleus from the Xisha
      Soft Coral Sinularia polydactyla.
AB  - Three new diterpenes, xishacorenes A-C, featuring an undescribed
      bicyclo[3.3.1]nonane nucleus bearing 1-vinyl and 13-[(E)-4-methylpenta-1,3-dien-1
      yl] alkyl chains, and a related monocyclic known compound, were isolated from the
      Xisha soft coral Sinularia polydactyla. The structures of xishacorenes A-C,
      including their absolute configurations, were elucidated by extensive
      spectroscopic analysis and TDDFT ECD calculations. The new compounds exhibit an
      interesting dose-dependent promotion effect on the ConA-induced T lymphocyte
      proliferation. A plausible biosynthetic pathway of xishacorenes A-C is proposed.

PMID- 28762747
TI  - Enantioselective Direct Synthesis of Free Cyclic Amines via Intramolecular
      Reductive Amination.
AB  - Chiral cyclic amines can be prepared via intramolecular reductive amination of N
      Boc-protected amino ketones in a one-pot process. With the complex of iridium and
      f-spiroPhos as the catalyst, a range of N-Boc-protected amino ketones are
      smoothly transformed into chiral cyclic free amines in high yields and excellent
      enantioselectivities (up to 97% ee). Moreover, this method can also be
      successfully applied to the synthesis of a kappa-opioid receptor selective
      antagonist, (S)-1.

PMID- 28762748
TI  - Adhesion, Stiffness, and Instability in Atomically Thin MoS2 Bubbles.
AB  - We measured the work of separation of single and few-layer MoS2 membranes from a
      SiOx substrate using a mechanical blister test and found a value of 220 +/- 35
      mJ/m2. Our measurements were also used to determine the 2D Young's modulus (E2D)
      of a single MoS2 layer to be 160 +/- 40 N/m. We then studied the delamination
      mechanics of pressurized MoS2 bubbles, demonstrating both stable and unstable
      transitions between the bubbles' laminated and delaminated states as the bubbles
      were inflated. When they were deflated, we observed edge pinning and a snap-in
      transition that are not accounted for by the previously reported models. We
      attribute this result to adhesion hysteresis and use our results to estimate the
      work of adhesion of our membranes to be 42 +/- 20 mJ/m2.

PMID- 28762750
TI  - Genome-Scale Modeling of NADPH-Driven beta-Lapachone Sensitization in Head and
      Neck Squamous Cell Carcinoma.
AB  - AIMS: The purpose of this study was to investigate differential nicotinamide
      adenine dinucleotide phosphate, reduced (NADPH) production between radiation
      sensitive and -resistant head and neck squamous cell carcinoma (HNSCC) cell lines
      and whether these differences are predictive of sensitivity to the
      chemotherapeutic beta-lapachone. RESULTS: We have developed a novel human genome
      scale metabolic modeling platform that combines transcriptomic, kinetic,
      thermodynamic, and metabolite concentration data. Upon incorporation of this
      information into cell line-specific models, we observed that the radiation
      resistant HNSCC model redistributed flux through several major NADPH-producing
      reactions. Upon RNA interference of canonical NADPH-producing genes, the
      metabolic network can further reroute flux through alternate NADPH biosynthesis
      pathways in a cell line-specific manner. Model predictions of perturbations in
      cellular NADPH production after gene knockdown match well with experimentally
      verified effects of beta-lapachone treatment on NADPH/NADP+ ratio and cell
      viability. This computational approach accurately predicts HNSCC-specific
      oxidoreductase genes that differentially affect cell viability between radiation
      responsive and radiation-resistant cancer cells upon beta-lapachone treatment.
      INNOVATION: Quantitative genome-scale metabolic models that incorporate multiple
      levels of biological data are applied to provide accurate predictions of
      responses to a NADPH-dependent redox cycling chemotherapeutic drug under a
      variety of perturbations. CONCLUSION: Our modeling approach suggests differences
      in metabolism and beta-lapachone redox cycling that underlie phenotypic
      differences in radiation-sensitive and -resistant cancer cells. This approach can
      be extended to investigate the synergistic action of NAD(P)H: quinone
      oxidoreductase 1 bioactivatable drugs and radiation therapy. Antioxid. Redox
      Signal. 29, 937-952.

PMID- 28762751
TI  - Associations between alcohol consumption and cardio-metabolic risk factors in
      young adults.
AB  - Introduction The benefits of alcohol consumption for cardiovascular and metabolic
      health may have been overstated due to inappropriate comparisons with abstainers
      and inadequate control for confounding factors including physical activity and
      mental health. We examined alcohol consumption and cardio-metabolic health in a
      cohort of young Australian adults overcoming these limitations. Methods Cross
      sectional data of a cohort of 2200 participants (age range 25-36 years) from the
      2004-06 Childhood Determinants of Adult Health were used. Alcohol consumption was
      assessed from questionnaire and cardio-metabolic risk factors were measured in
      clinics. Linear and log binomial regression were used to examine total alcohol
      consumption (categories: none 0 g/day; light >0-10 g/day [reference]; moderate
      >10-20 g/day; heavy >20-30 g/day; very heavy >30 g/day) against dichotomous
      metabolic syndrome and its components: waist circumference, triglycerides, high
      density lipoprotein cholesterol, blood pressure and glucose. Covariates included
      socio-demographics, smoking, diet, physical activity, fitness, depression and
      anxiety. Results Of the 2220 participants (48% males, mean (standard deviation)
      age 29.5 (2.5) years), most were classified in the 'light drinking' group
      (54.2%), less were in the 'non-drinking' (13.2%), 'heavy' (5.2%) or 'very heavy'
      (5.5%) drinking groups. Only moderate drinking was associated with a
      significantly lower prevalence of metabolic syndrome (prevalence ratio = 0.64, p
      < 0.05) compared with light drinking. Higher levels of alcohol consumption were
      associated with higher high-density lipoprotein cholesterol (beta = 0.05, ptrend
      < 0.001). Very heavy compared to light drinkers had higher systolic (beta = 3.01
      mm Hg, p < 0.01) and diastolic (beta = 2.07 mm Hg, p < 0.05) blood pressure.
      Conclusion Moderate alcohol consumption was associated with a lower prevalence of
      MetS, and more favourable levels of lipids but not glucose or blood pressure even
      when compared to light consumption and with account for a range of confounding
      factors.

PMID- 28762749
TI  - Thrombospondin-1, Free Radicals, and the Coronary Microcirculation: The Aging
      Conundrum.
AB  - SIGNIFICANCE: Successful matching of cardiac metabolism to perfusion is
      accomplished primarily through vasodilation of the coronary resistance
      arterioles, but the mechanism that achieves this effect changes significantly as
      aging progresses and involves the contribution of reactive oxygen species (ROS).
      Recent Advances: A matricellular protein, thrombospondin-1 (Thbs-1), has been
      shown to be a prolific contributor to the production and modulation of ROS in
      large conductance vessels and in the peripheral circulation. Recently, the
      presence of physiologically relevant circulating Thbs-1 levels was proven to also
      disrupt vasodilation to nitric oxide (NO) in coronary arterioles from aged
      animals, negatively impacting coronary blood flow reserve. CRITICAL ISSUES: This
      review seeks to reconcile how ROS can be successfully utilized as a substrate to
      mediate vasoreactivity in the coronary microcirculation as "normal" aging
      progresses, but will also examine how Thbs-1-induced ROS production leads to
      dysfunctional perfusion and eventual ischemia and why this is more of a concern
      in advancing age. FUTURE DIRECTIONS: Current therapies that may effectively
      disrupt Thbs-1 and its receptor CD47 in the vascular wall and areas for future
      exploration will be discussed. Antioxid. Redox Signal. 27, 785-801.

PMID- 28762753
TI  - Migraine in mitochondrial disorders: Prevalence and characteristics.
AB  - Background Migraine is a well-known feature of mitochondrial disorders (MDs).
      However, no systematic epidemiological data are available in large populations of
      patients. Aims The aim of this cross-sectional cohort study was to describe the
      prevalence and migraine characteristics in a large cohort of patients with
      mitochondrial encephalomyopathies. Methods We studied 93 consecutive patients
      with characterised MDs referred to our Neuromuscular Unit during a 12-month
      period. All patients (age range = 16-78 years; 31 men; 58 progressive external
      ophthalmoplegia [PEO], 12 myoclonic epilepsy with ragged red fibres [MERRF],
      eight mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
      [MELAS], two mitochondrial neurogastrointestinal encephalomyopathy [MNGIE] and 13
      other MDs) underwent a structured diagnostic headache interview using an
      operational diagnostic tool following the IHS criteria. If they met the criteria
      for migraine, they were included in the 'Migraine Group'. The other patients were
      counted in the 'No Migraine Group'. Patient demographic and migraine
      characteristics were examined. Clinical, neuroradiological and neurophysiological
      data were compared between groups. Results Migraine was reported in 35.5% of
      patients. Migraine without aura was the most common headache (81.8%). The
      migraine group showed younger age ( P < 0.01), increased prevalence of epilepsy (
      P = 0.01), myoclonus ( P = 0.03), stroke-like episodes ( P = 0.03) and decreased
      prevalence of muscle weakness ( P < 0.01). Multivariate analysis showed that
      migraine was positively associated with absence of muscle weakness ( P = 0.04)
      and presence of EEG abnormalities ( P = 0.02). Conclusion Migraine has a higher
      prevalence in MDs compared with general population-based data, independently from
      genotype or phenotype. Migraine is not merely a phenotypic aspect of specific MDs
      but is rather the expression of vulnerability of the central nervous system,
      probably directly related with defects of the respiratory chain.

PMID- 28762752
TI  - Oxidative Stress in Mesenchymal Stem Cell Senescence: Regulation by Coding and
      Noncoding RNAs.
AB  - SIGNIFICANCE: Mesenchymal stem cells (MSCs), adult stem cells with the potential
      of differentiation into mesodermal lineages, play an important role in tissue
      homeostasis and regeneration. In different organs, a subpopulation of MSCs is
      located near the vasculature and possibly represents the original source of
      lineage-committed mesenchymal progenitors. Recent Advances: The plasticity and
      immune characteristics of MSCs render them a preferential tool for regenerative
      cell therapy. CRITICAL ISSUES: The culture expansion needed before MSC
      transplantation is associated with cellular senescence. Moreover, accelerated
      senescence of the total and perivascular MSC pool has been observed in humans and
      mouse models of premature aging disorders. MSC dysfunction is acknowledged as a
      culprit for the aging-associated degeneration of mesodermal tissues, but the
      underlying epigenetic pathways remain elusive. This article reviews current
      understanding of mechanisms impinging on MSC health, including oxidative stress,
      Nrf2-antioxidant responsive element activity, sirtuins, noncoding RNAs, and PKCs.
      FUTURE DIRECTIONS: We provide evidence that epigenetic profiling of MSCs is
      utilitarian to the prediction of therapeutic outcomes. In addition, strategies
      that target oxidative stress-associated mechanisms represent promising approaches
      to counteract the detrimental effect of age and senescence in MSCs.-Antioxid.
      Redox Signal. 29, 864-879.

PMID- 28762754
TI  - Flow-Responsive Vascular Endothelial Growth Factor Receptor-Protein Kinase C
      Isoform Epsilon Signaling Mediates Glycolytic Metabolites for Vascular Repair.
AB  - AIMS: Hemodynamic shear stress participates in maintaining vascular redox status.
      Elucidating flow-mediated endothelial metabolites enables us to discover
      metabolic biomarkers and therapeutic targets. We posited that flow-responsive
      vascular endothelial growth factor receptor (VEGFR)-protein kinase C isoform
      epsilon (PKCE)-6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3)
      signaling modulates glycolytic metabolites for vascular repair. RESULTS:
      Bidirectional oscillatory flow (oscillatory shear stress [OSS]: 0.1 +/- 3 dyne.cm
      2 at 1 Hz) upregulated VEGFR-dependent PKCE expression to a greater degree than
      did unidirectional pulsatile flow (pulsatile shear stress [PSS]: 23 +/- 8 dyne.cm
      2 at 1 Hz) in human aortic endothelial cells (p < 0.05, n = 3). PSS and OSS
      further upregulated PKCE-dependent PFKFB3 expression for glycolysis (p < 0.05, n
      = 4). Constitutively active PKCE increased, whereas dominant-negative PKCE
      reduced both basal and maximal extracellular acidification rates for glycolytic
      flux (p < 0.01, n = 4). Metabolomic analysis demonstrated an increase in PKCE
      dependent glycolytic metabolite, dihydroxyacetone (DHA), but a decrease in
      gluconeogenic metabolite, aspartic acid (p < 0.05 vs. control, n = 6). In a New
      Zealand White rabbit model, both PKCE and PFKFB3 immunostaining was prominent in
      the PSS- and OSS-exposed aortic arch and descending aorta. In a transgenic Tg(flk
      1:EGFP) zebrafish model, GATA-1a morpholino oligonucleotide injection (to reduce
      viscosity-dependent shear stress) impaired vascular regeneration after tail
      amputation (p < 0.01, n = 20), which was restored with PKCE messenger RNA (mRNA)
      rescue (p < 0.05, n = 5). As a corollary, siPKCE inhibited tube formation and
      vascular repair, which were restored by DHA treatment in our Matrigel and
      zebrafish models. Innovation and Conclusion: Flow-sensitive VEGFR-PKCE-PFKFB3
      signaling increases the glycolytic metabolite, dihydroxyacetone, to promote
      vascular repair. Antioxid. Redox Signal. 28, 31-43.

PMID- 28762755
TI  - AstraZeneca and Covance Laboratories Clinical Bioanalysis Alliance: an
      evolutionary outsourcing model.
AB  - The AstraZeneca and Covance Laboratories Clinical Bioanalysis Alliance (CBioA)
      was launched in 2011 after a period of global economic recession. In this
      challenging environment, AstraZeneca elected to move to a full and centralized
      outsourcing model that could optimize the number of people supporting
      bioanalytical work and reduce the analytical cost. This paper describes the key
      aspects of CBioA, the innovative operational model implemented, and our ways of
      ensuring this was much more than simply a cost reduction exercise. As we have
      recently passed the first 5-year cycle, this paper also summarizes some of the
      concluding benefits, wins and lessons learned, and how we now plan to extend and
      develop the relationship even further moving into a new clinical laboratory
      partnership.

PMID- 28762757
TI  - Molecular characterization and phylogenetic analysis of a virulent Marek's
      disease virus field strain in broiler chickens in Japan.
AB  - Marek's disease is a lymphoproliferative disease causing a serious threat in
      poultry production. Field strains of Marek's disease virus (MDVs) are
      continuously re-emerging, causing great economical losses to the poultry industry
      worldwide in spite of the intensive vaccination and restrictive management policy
      used. Histopathological and molecular characterizations of MDVs are essential for
      monitoring the changes of viruses and evaluating the effectiveness of existing
      vaccines. During 2016, 190 visceral tumour tissues representing 30 vaccinated
      chicken flocks from the Gifu prefecture, Japan, were analysed. A pathological
      examination revealed the presence of lymphoproliferative lesions in the visceral
      organs. Polymerase chain reaction screening of tissue specimens using specific
      primers for avian leucosis virus, reticuloendotheliosis virus, and MDV was
      positive only for MDV. The polymerase chain reaction products of meq, pp38, virus
      induced IL-8 homology, and glycoprotein MDV genes were sequenced and used for
      homology, phylogenetic, and similarity level analysis with the published
      reference of MDVs in the database. The results revealed high similarity between
      the field isolates, vv and vv+ strains of MDV from the USA and China. Several
      point mutations in the nucleotide sequence of the field isolates and their
      deduced amino acid sequences were detected in those genes. The present molecular
      analyses indicated that nucleotide and amino acid changes could be valuable
      criteria for differentiation and determination of the pathogenicity and
      oncogenicity of MDVs according to the Avian Disease and Oncology Laboratory
      pathotyping in vivo studies. Furthermore, the results suggest that development of
      a new vaccine must be considered to overcome this devastating avian oncogenic
      viral disease.

PMID- 28762756
TI  - Intranasal Oxytocin Selectively Modulates Large-Scale Brain Networks in Humans.
AB  - A growing body of evidence indicates that the neuropeptide oxytocin (OT) alters
      the neural correlates of socioemotional and salience processing. Yet the effects
      of OT over important large-scale networks involved in these processes, such as
      the default mode (DM), ventral attention (VA), and cingulo-opercular (CO)
      networks, remain unknown. Therefore, we conducted a placebo-controlled crossover
      study with intranasal 24 IU OT in 38 healthy male subjects using a resting-state
      functional magnetic resonance imaging paradigm to investigate its impact over
      these three networks candidates. To understand the underlying mechanisms of the
      neuropeptide, we compared the intranetwork connectivity for each network
      candidate and also the internetwork connectivity across all networks between both
      treatment conditions. Based on the relevance of interindividual factors for OT
      effects, we correlated individual network changes with behavioral performance in
      a decision-making task and with impulsivity scores. Our results show that OT
      mainly alters connectivity in the VA, on one side reducing the coupling to
      regions that typically form the nodes of DM, an introspective and self
      referential network, and on the other side increasing the coupling to the edges
      of the CO, which is involved in salience processing. The results of the
      internetwork analyses confirmed the specificity of the OT effects. Indeed, we
      observed significant correlations with the erroneous performance during decision
      making but not with the obtained impulsivity scores. Overall, our data support
      that the modulation of functional connectivity within the VA is a basic mechanism
      by which OT directs attentional resources from internal to external cues,
      preparing the brain for context-dependent salience processing.

PMID- 28762758
TI  - Outsourcing bioanalytical services at Janssen Research and Development: the
      sequel anno 2017.
AB  - The strategy of outsourcing bioanalytical services at Janssen has been evolving
      over the last years and an update will be given on the recent changes in our
      processes. In 2016, all internal GLP-related activities were phased out and this
      decision lead to the re-orientation of the in-house bioanalytical activities. As
      a consequence, in-depth experience with the validated bioanalytical assays for
      new drug candidates is currently gained together with the external partner, since
      development and validation of the assay and execution of GLP preclinical studies
      are now transferred to the CRO. The evolution to externalize more bioanalytical
      support has created opportunities to build even stronger partnerships with the
      CROs and to refocus internal resources. Case studies are presented illustrating
      challenges encountered during method development and validation at preferred
      partners when limited internal experience is obtained or with introduction of new
      technology.

PMID- 28762759
TI  - Adenosine-to-Inosine RNA Editing in Health and Disease.
AB  - SIGNIFICANCE: Adenosine deamination in transcriptome results in the formation of
      inosine, a process that is called A-to-I RNA editing. Adenosine deamination is
      one of the more than 140 described RNA modifications. A-to-I RNA editing is
      catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes and is essential
      for life. Recent Advances: Accumulating evidence supports a critical role of RNA
      editing in all aspects of RNA metabolism, including mRNA stability, splicing,
      nuclear export, and localization, as well as in recoding of proteins. These
      advances have significantly enhanced the understanding of mechanisms involved in
      development and in homeostasis. Furthermore, recent studies have indicated that
      RNA editing may be critically involved in cancer, aging, neurological,
      autoimmune, or cardiovascular diseases. CRITICAL ISSUES: This review summarizes
      recent and significant achievements in the field of A-to-I RNA editing and
      discusses the importance and translational value of this RNA modification for
      gene expression, cellular, and organ function, as well as for disease
      development. FUTURE DIRECTIONS: Elucidation of the exact RNA editing-dependent
      mechanisms in a single-nucleotide level may pave the path toward the development
      of novel therapeutic strategies focusing on modulation of ADAR function in the
      disease context. Antioxid. Redox Signal. 29, 846-863.

PMID- 28762760
TI  - Outsourcing of bioanalysis at GSK: a hybrid approach with a robust support model.

PMID- 28762761
TI  - A systematic review of cardiac rehabilitation registries.
AB  - Introduction Despite cardiac rehabilitation being recommended in clinical
      practice guidelines internationally these services are underutilised, programmes
      are not standardised and quality improvement methods and outcomes are rarely
      published. National registries are an important strategy to characterise service
      delivery, quality and outcomes, yet the number, type and components of national
      cardiac rehabilitation registries have not been reported. Aims To identify and
      describe national and international cardiac rehabilitation registries, and
      summarise their key features. Methods We systematically reviewed the literature
      reporting on cardiac rehabilitation registries at a national and international
      level. A search of four databases was conducted in July 2016, with two reviewers
      independently screening titles/abstracts and full texts for inclusion. Data were
      extracted from included studies, independently checked by a second reviewer and
      synthesised qualitatively. Results Eleven articles were included in the review
      comprising seven national registries and one international registry (of 12
      European countries) for a total sample of 265,608 patients. Data were most
      commonly provided to the registry by a web-based application, and included
      individual-level data (i.e. sociodemographic characteristics, medical history,
      and clinical measurements). When reported, service-level data most commonly
      included wait times, programme enrolment and completion. The overarching
      governance, funding modes (e.g. industry ( n = 2), government ( n = 1)), and
      incentives for registry participation (e.g. benchmarking, financial
      reimbursement, or mandatory requirement) varied widely. Conclusion The use of
      national and international registries for characterising cardiac rehabilitation
      and providing a benchmark for quality improvement is in its early stages but
      shows promise for national and global benchmarking.

PMID- 28762762
TI  - GDF-15 and TRAIL-R2 are powerful predictors of long-term mortality in patients
      with acute myocardial infarction.
AB  - Background The Proximity Extension Assay proteomics chip provides a large-scale
      analysis of 92 biomarkers linked to cardiovascular disease or inflammation. We
      aimed to identify the biomarkers that best predicted long-term all-cause
      mortality in patients with acute myocardial infarction. Methods In this
      prospective cohort study, 92 biomarkers were analysed in 847 consecutive patients
      from the Vastmanland Myocardial Infarction Study with a median follow-up of 6.9
      years. Results The mean (+/- standard deviation) age of the patients was 70
      (11.8) years and 32.7% were female. Two hundred and seven patients had died after
      follow-up. The biomarkers most strongly linked to all-cause mortality were growth
      differentiation factor 15 (GDF-15) and tumour necrosis factor-related apoptosis
      inducing ligand receptor 2 (TRAIL-R2). Cox regression analysis showed that GDF-15
      (hazard ratio 1.25 per unit change, 95% confidence interval, 1.02-1.53, p =
      0.031) and TRAIL-R2 (hazard ratio 1.37 per unit change, 95% confidence interval
      1.12-1.67, p = 0.002) were independent predictors of long-term all-cause
      mortality after adjusting for age, gender, diabetes, previous myocardial
      infarction, stroke, heart failure, hypertension, smoking, hypercholesterolaemia,
      body mass index, ST-elevation myocardial infarction, left ventricular ejection
      fraction, troponin I, estimated glomerular filtration rate, N-terminal pro-brain
      natriuretic peptide and C-reactive protein. The combination of GDF-15 and TRAIL
      R2 with established risk factors and biomarkers showed a discriminating accuracy
      of separating survivors from non-survivors with a cross-validated area under the
      receiving operating characteristics curve of 0.88 within five years. Conclusion
      GDF-15 and TRAIL-R2 were the most powerful Proximity Extension Assay chip
      biomarkers in predicting long-term all-cause mortality in patients with acute
      myocardial infarction.

PMID- 28762763
TI  - Opening the Regulatory T Cell Toolbox.

PMID- 28762764
TI  - Stretching to Understand How Proteostasis and the Unfolded Protein Response
      Regulate Lung Injury.

PMID- 28762765
TI  - Erratum: Deficiency in Nrf2-GSH Signaling Impairs Type II Cell Growth and
      Enhances Sensitivity to Oxidants.

PMID- 28762767
TI  - Erratum: Modified High-Molecular-Weight Hyaluronan Promotes Allergen-Specific
      Immune Tolerance.

PMID- 28762768
TI  - Lung Cell-Specific Cre Deleter Mouse Strains: Going Back to Move Forward.

PMID- 28762769
TI  - The Runt of the Litter-Stronger than We Thought?

PMID- 28762770
TI  - Groundhog Day for Rodent Models of Acute Lung Injury: Clear Relevance or Renewed
      Debate?

PMID- 28762771
TI  - Lung Interstitial Macrophages Redefined: It Is Not That Simple Anymore.

PMID- 28762772
TI  - The -Omic Approach to Understanding Glucocorticoid Effects in Smooth Muscle:
      Diving for Pearls.

PMID- 28762773
TI  - Partners in Crime: Epithelial Priming of Macrophages during Viral Infection.

PMID- 28762775
TI  - Diagnostic experience of patients with fibromyalgia - A meta-ethnography.
AB  - Objective To examine how individuals experience the process and consequences of
      receiving a diagnosis of fibromyalgia syndrome. Methods A systematic literature
      search of qualitative studies up to May 2016 was performed. Twenty-eight reports
      including information on patients' diagnostic experiences were subjected to an
      interpretive analysis in accordance with the principles of meta-ethnography.
      Results Years were normally spent consulting specialists in an attempt to confirm
      the reality of symptoms and make sense of the illness. Great relief was felt at
      finally achieving the fibromyalgia syndrome diagnosis. However, relief waned when
      therapies proved ineffective. Health professionals and others questioned whether
      individuals were genuinely ill, that the illness had a psychological nature, and
      whether they were doing their best to recover. The diagnosis did not provide a
      meaningful explanation of individuals' suffering and had limited power to
      legitimate illness. Patients felt blamed for their failure to recover,
      threatening their personal credibility and moral identity. Conclusion The
      fibromyalgia syndrome diagnosis has limitations in validating and making sense of
      patients' illness experiences and in providing social legitimation of their
      illness. Social relationships are strained during the diagnostic process and in
      the course of ineffective therapies.

PMID- 28762774
TI  - Hyperoxidation of Peroxiredoxins: Gain or Loss of Function?
AB  - SIGNIFICANCE: In 2003, structural studies revealed that eukaryotic 2-Cys
      peroxiredoxins (Prx) have evolved to be sensitive to inactivation of their
      thioredoxin peroxidase activity by hyperoxidation (sulfinylation) of their
      peroxide-reacting catalytic cysteine. This was accompanied by the unexpected
      discovery, that the sulfinylation of this cysteine was reversible in vivo and the
      identification of a new enzyme, sulfiredoxin, that had apparently co-evolved
      specifically to reduce hyperoxidized 2-Cys Prx, restoring their peroxidase
      activity. Together, these findings have provided the impetus for multiple studies
      investigating the purpose of this reversible, Prx hyperoxidation. Recent
      Advances: It has been suggested that inhibition of the thioredoxin peroxidase
      activity by hyperoxidation can both promote and inhibit peroxide signal
      transduction, depending on the context. Prx hyperoxidation has also been proposed
      to protect cells against reactive oxygen species (ROS)-induced damage, by
      preserving reduced thioredoxin and/or by increasing non-peroxidase chaperone or
      signaling activities of Prx. CRITICAL ISSUES: Here, we will review the evidence
      in support of each of these proposed functions, in view of the in vivo contexts
      in which Prx hyperoxidation occurs, and the role of sulfiredoxin. Thus, we will
      attempt to explain the basis for seemingly contradictory roles for Prx
      hyperoxidation in redox signaling. FUTURE DIRECTIONS: We provide a rationale,
      based on modeling and experimental studies, for why Prx hyperoxidation should be
      considered a suitable, early biomarker for damaging levels of ROS. We discuss the
      implications that this has for the role of Prx in aging and the detection of
      hyperoxidized Prx as a conserved feature of circadian rhythms. Antioxid. Redox
      Signal. 28, 574-590.

PMID- 28762776
TI  - Diabetes management in Senegalese families: A dyadic-narrative illustration.
AB  - Objectives In many Sub-Saharan African cultures, diabetes self-management
      behaviors such as dietary adherence do not occur in isolation but are carried out
      in the context of local culture, a significant factor in shaping those health
      behaviors. Methods Using a family-based narrative approach, we explore how
      Senegalese families manage diabetes. We interviewed twenty people living with
      diabetes and selected family caregivers from MBour, Senegal. Results We found
      that people living with diabetes experienced physical, emotional, and financial
      stressors as a result of managing their condition. In addition, family caregivers
      play an important role in managing their family member's diabetes. Discussion The
      act of caregiving affects caregiver diabetes prevention behaviors. In some cases,
      this caregiving role leads to an increase of healthy behaviors such as reducing
      dietary sugar; however, in some cases, caregivers do not see the need to engage
      in healthy behaviors. Diabetes prevention and management interventions that
      support both Senegalese people living with diabetes and their family caregivers
      are warranted.

PMID- 28762777
TI  - Occurrence and Health Risk of Patulin and Pyrethroids in Fruit Juices Consumed in
      Bangkok, Thailand.
AB  - The mycotoxin patulin (PAT) is well known as a natural contaminant of apple- and
      other fruit-based products. Pesticides are a group of chemicals abundantly used
      in agriculture to maximize productivity by protecting crops from pests and weeds.
      Because of their harmful health effects, PAT and pesticides are strictly
      monitored. The current study was undertaken to investigate the significance of
      PAT and pyrethroid insecticide contamination in a variety of fruit juices in
      Bangkok. To do this, a total of 200 fruit juice samples, consisting of 40 samples
      each of apple, apricot, peach, pineapple, and grape juice, were collected from
      supermarkets in Bangkok, Thailand. PAT contamination in a variety of fruit juices
      was detected using validated liquid chromatography-tandem mass spectrometry, and
      pyrethroid insecticides (cypermethrin, cyfluthrin, and flumethrin) were analyzed
      using a gas chromatography equipped with micro-electron capture detector. The
      survey found that PAT concentrations were lower than the maximum residue limit
      established by European Union. The results of the present study suggest that the
      risk of exposure to harmful levels of PAT, cypermethrin, cyfluthrin, and
      flumethrin in fruit juices is very low in urban areas of Thailand.

PMID- 28762778
TI  - Epigenomic analysis in a cell-based model reveals the roles of H3K9me3 in breast
      cancer transformation.
AB  - AIM: Epigenetic marks are critical regulators of chromatin and gene activity.
      Their roles in normal physiology and disease states, including cancer
      development, still remain elusive. Herein, the epigenomic change of H3K9me3, as
      well as its potential impacts on gene activity and genome stability, was
      investigated in an in vitro breast cancer transformation model. METHODS: The
      global H3K9me3 level was studied with western blotting. The distribution of
      H3K9me3 on chromatin and gene expression was studied with ChIP-Seq and RNA-Seq,
      respectively. RESULTS: The global H3K9me3 level decreases during transformation
      and its distribution on chromatin is reprogrammed. By combining with TCGA data,
      we identified 67 candidate oncogenes, among which five genes are totally novel.
      Our analysis further links H3K9me3 with transposon activity, and suggests H3K9me3
      reduction increases the cell's sensitivity to DNA damage reagents. CONCLUSION:
      H3K9me3 reduction is possibly related with breast cancer transformation by
      regulating gene expression and chromatin stability during transformation.

PMID- 28762779
TI  - Editorial Comment on: Induction and Maintenance Adjuvant Mitomycin C Topical
      Therapy for Upper Tract Urothelial Carcinoma: Tolerability and Intermediate Term
      Outcomes by Metcalfe et al.

PMID- 28762780
TI  - Applications of prebiotics in food industry: A review.
AB  - Benefits of prebiotics for stimulating a healthy intestinal tract are well known.
      From suppression of pathogens to proliferation of indigenous bacteria of
      intestines, prebiotics have it all. Since the research on the scope of prebiotics
      is expanding, new applications are coming up every day thus upgrading the choices
      consumer has for a healthy living. Incorporation of prebiotics in a wide range of
      products that food industry offers on shelf is an innovative way to replace fat
      and sugars along with enhancing the mouthfeel by providing better tongue
      lubrication. In some cases, the thermal stability of the product is improved
      along with other sensory, textural and physiological benefits. This paper gives
      an overview of the various prebiotics available from different sources and their
      applications in various segments of food industry, notably dairy, beverage,
      processed fruit-vegetable, bakery, confectionary, extruded snack, sweetener,
      infant formula, pet food and livestock industry. The effects observed on addition
      of various prebiotics are also elaborated.

PMID- 28762781
TI  - Application of the Hands-On Donkey Tool for Assessing the Welfare of Working
      Equids at Tuliman, Mexico.
AB  - Equids are still used for diverse chores in Mexico and are essential for the
      livelihoods of numerous families. Appropriate health and behavior are
      prerequisites for performing work without affecting welfare. This study aimed to
      assess the welfare of working equids in Tuliman, applying the hands-on donkey
      tool. This tool evaluates five dimensions (behavior, body condition score [BCS],
      wounds, lameness, and other health issues) and was applied to 438 working equids
      (horses, mules, and donkeys). The Kruskall-Wallis test was applied to investigate
      differences between species and sex. Donkeys were more common; they also
      presented more positive behaviors and less lameness (p < 0.05). No differences
      were found for BCS among species on a scale ranging from 1 to 5 (mean BCS for
      donkeys = 1.9; mules = 2; and horses = 1.8). Mares had significantly lower BCS
      (mean = 1.5) than stallions (p < 0.05) and geldings (mean = 1.9). Overall mules
      had better welfare evaluations. The tool allowed detection of welfare issues in
      working equids; a practical outcome would be implementing local welfare
      strategies according to its results.

PMID- 28762782
TI  - PAP Therapy-Tips for Troubleshooting to Address Problems with Use.

PMID- 28762783
TI  - One-off Spirometry Is Insufficient to Rule In or Rule Out Mild to Moderate
      Chronic Obstructive Pulmonary Disease.

PMID- 28762785
TI  - Preterm Birth, Bronchopulmonary Dysplasia, and Long-Term Respiratory Disease.

PMID- 28762784
TI  - Next-Generation Sequencing of Endobronchial Ultrasound Transbronchial Needle
      Aspiration Specimens in Lung Cancer.

PMID- 28762786
TI  - More Than Meets the Eye: Cigarette Smoke Induces Genomic Changes in the Small
      Airway Epithelium Independent of Histologic Changes.

PMID- 28762787
TI  - On the "TRAIL" of a Killer: MMP12 in Lung Cancer.

PMID- 28762789
TI  - Myeloid-derived Suppressor Cells in Sepsis.

PMID- 28762788
TI  - Leveraging Transcriptomics to Disentangle Sepsis Heterogeneity.

PMID- 28762790
TI  - Erratum: Carbon Monoxide Poisoning: Pathogenesis, Management, and Future
      Directions of Therapy.

PMID- 28762791
TI  - An NLRP3, IL-1beta, Neutrophil Axis in the Respiratory Tract Leaves You
      Breathless.

PMID- 28762793
TI  - Madness and Society in Eighteenth-Century Scotland R. A. HoustonMadness and
      Society in Eighteenth-Century Scotland R. A. Houston Oxford: Clarendon Press,
      2000, xi + 450 p., L55.00.

PMID- 28762794
TI  - Ibn Zuhr (Avenzoar)'s Description of a Verrucous Malignancy of the Colon (with an
      English Translation from the Arabic and notes on its Hebrew and Latin Versions).
AB  - Ibn Zuhr (ca. 1091-1161) is the most important physician of Muslim Spain. His
      Kitab al-Taysir, translated into Hebrew and Latin, is principally a manual of
      therapeutics containing descriptions of clinical cases. His description "On
      Verrucae (thaalil) that Occur in the Stomach [sic]," which deals with an
      emaciated Berber who evacuates a tumour the size of an apple in his stools,
      represents the first detailed report of a cancer of the colon. Latin and Hebrew
      translations of this report are close to the Arabic, but it is doubtful that the
      Latin text is based on the Hebrew. The possibility of an intermediate Judeo
      Arabic text should be considered.

PMID- 28762795
TI  - "Filling the Gaps": Canadian Voluntary Nurses, the 1917 Halifax Explosion, and
      the Influenza Epidemic of 1918.
AB  - During the Great War, St. John Ambulance established a reserve of approximately
      2,000 casually trained nursing volunteers as Voluntary Aid Detachment nurses, or
      VADs, who assisted in military hospitals at home and overseas. During the 1917
      Halifax explosion, and the 1918 influenza epidemic, VADs also provided
      substantial assistance to qualified medical and nursing personnel. This paper
      considers their record during these specific events, arguing that despite the
      potential for VADs to undermine the status and job security of qualified graduate
      nurses, they proved instead both a valuable asset and a positive influence for
      the future development of Canadian nursing.

PMID- 28762796
TI  - Special Supplement: "Creative/Artistic Narratives of Illness".

PMID- 28762798
TI  - Love, Sex and Marriage Julie Coleman and edited by C.C. Barfoot, Hans Bertens,
      Theo D'haen and Erik KooperLove, Sex and Marriage Julie Coleman and edited by
      C.C. Barfoot, Hans Bertens, Theo D'haen and Erik Kooper Costerus New Series 118
      Amsterdam-Atlanta, Rodopi 1999,599 p., US $133.00.

PMID- 28762802
TI  - Dissertations.

PMID- 28762801
TI  - Medical Geography in Historical Perspective Medical History, Supplement No. 20
      Nicolaas A. Rupke, ed.Medical Geography in Historical Perspective Medical
      History, Supplement No. 20 Nicolaas A. Rupke, ed. London: The Wellcome Trust
      Centre for the History of Medicine at UCL, 2000, xii + 227 p., US $50.

PMID- 28762803
TI  - A Short History of Neurology: The British Contribution 1660-1910 E. Clifford
      Rose, ed.A Short History of Neurology: The British Contribution 1660-1910 E
      Clifford Rose, ed. Oxford: Butterworth-Hainemarm, 1999,282 p., L25.00.

PMID- 28762809
TI  - John Hutchinson.

PMID- 28762810
TI  - Abulcasis, Avicenne et Galien. La savoir d'un medecin juif au miroir d'une
      expertise medico-legale de la fin du XIVe siecle.

PMID- 28762812
TI  - Singular Selves. Historical Issues and Contemporary Debates in Immunology. A. M.
      Moulin and A. Cambrosio, eds.Singular Selves. Historical Issues and Contemporary
      Debates in Immunology. A. M. Moulin and A. Cambrosio, eds. Amsterdam: Elsevier,
      2001,303 p., Euro 49.

PMID- 28762815
TI  - Note de la Redacteur.

PMID- 28762813
TI  - CSHM/SCHM Presidential Address, Discours Presidentiel, 26 May 2001: The Quota:
      "An Equally Serious Problem" for Us All.
AB  - The author explores the question-was a quota applied to the admission of women to
      the medical school of the University of Toronto? She uses a variety of sources,
      including class photographs, archives, statistics, personal recollections, and
      oral history. The existence of a quota from 1944 to 1968 is inferred from
      statistical patterns and confirmed by a surprising source. In closing, the
      historiographie implications of this project for research on other politically
      charged topics are considered.

PMID- 28762817
TI  - Queen Victoria's Gene: Haemophilia and the Royal Family D. M. Potts and W. T. W.
      PottsQueen Victoria's Gene: Haemophilia and the Royal Family D. M. Potts and W.
      T. W. Potts Phoenix Mill, Thrupp, Stroud, Gloucestershire: Sutton, 1995, viii +
      183 p., US $17.95.

PMID- 28762819
TI  - The Historiography of Psychoanalysis Paul RoazenThe Historiography of
      Psychoanalysis Paul Roazen New Brunswick, N.J.: Transaction, 2001, xiii + 480 p.,
      US $49.95.

PMID- 28762821
TI  - Roy Porter (1946-2002).

PMID- 28762822
TI  - Connecting Healthcare. Sydney 11-12 February 2009.

PMID- 28762823
TI  - Cassandra Jordan: NSW State Liaison Officer, HIMJ.

PMID- 28762824
TI  - The Role of the Health Information Manager in a Research-Based Information
      Technology Project.
AB  - Information technology advances in healthcare provide many and varied
      opportunities for the Health Information Manager. Here is one example involving a
      Melbourne-based research project and an innovative approach to patient
      information delivery. The research project area of study is multimedia content
      delivery in the following applications: as an adjunct to the surgical informed
      consent process, patient information or instruction presentation and clinical
      education. The objective is to develop evidence-based, effective and accessible
      information and knowledge resources for patients and health care providers.

PMID- 28762825
TI  - Julie Smalley: Adventures of a Health Information Manager in the United Kingdom.

PMID- 28762826
TI  - Managing Change Proactively within the Current HIM Professional Domain.

PMID- 28762827
TI  - A New Era in Clinical Communications: A Report on the Past Year's Work at NEHTA.
AB  - Across Australia there is a groundswell of support for a better more connected
      healthcare system. More than 80 per cent of Australians are in favour of
      electronic health records and the sector is increasingly aware of the safety and
      quality benefits that e-health can deliver. On behalf of the governments of
      Australia, the National E-Health Transition Authority (NEHTA) is developing a
      national e-health infrastructure that will underpin the success of a connected
      healthcare system. This involves a body of work that includes clinical
      terminologies, unique healthcare identification and the development and
      recommendation of standards for the safe transmission and access of healthcare
      information. Read an update of NEHTA's work and progress in 2008.

PMID- 28762828
TI  - Ist IFHRO SEAR Conference: Consolidation and Strengthening in Health Information
      Management for the Benefit of Health Safety Environment to Support the Millenium
      Development Goals among IFHRO SEAR Countries in the 21st Century.

PMID- 28762829
TI  - Professional Practice: Enterprise Architecture in the Information Services
      Division, Ministry of Health Holdings, Singapore.

PMID- 28762830
TI  - Project Manager, Health Care Safety and Quality Unit, Australian Institute of
      Health and Welfare Junior Vice-President, HIMAA Board of Directors.

PMID- 28762831
TI  - Barbara Armstrong: National Administrator, Australian Homoeopathic Association.

PMID- 28762832
TI  - A World First in Cancer Data Collection Trial.
AB  - An innovative study to collect comprehensive cancer data is underway in the
      Barwon Southwestern region of Victoria. The Evaluation of Cancer Outcomes (ECO)
      Trial involves the collection of a nationally developed and agreed set of
      clinical cancer data items across the region. Cancer is the leading cause of
      death in Australia and cancer surveillance relies heavily on accurate incidence
      and mortality data collection. The Victorian Government and Victorian Department
      of Human Services recently identified a lack of useful data surrounding patients
      diagnosed with cancer, their treatment, clinical course and outcomes. This
      article discusses the need for an improved and extended cancer data collection
      model and highlights the importance of timely population data on processes and
      outcomes of cancer.

PMID- 28762833
TI  - Changing Roles of Health Information Managers: An Education Perspective.
AB  - Health information management graduates are employed across health, education,
      corporate and other sectors. Common to all health information management
      professionals are foundational skills and knowledge in health sciences,
      information and management. Unique to each individual is their ongoing education
      and professional development; professional growth motivated by interest, change
      and/or opportunity. This presents both challenge and opportunity in the design
      and content of educational programs. The establishment of the Australian Health
      Informatics Education Council (AHIEC) (formerly the National Health Informatics
      Education Committee) provides both framework and opportunity for new ways and
      approaches to health informatics education in Australia. There are however
      process matters that proposed changes to education programs need to acknowledge.

PMID- 28762834
TI  - Duty of Confidentiality and HIV/AIDS: PD v Harvey.
AB  - The issue of doctor-patient confidentiality in situations where the doctor can
      reasonably foresee that third parties associated with the patient could be put at
      risk by the patient's medical status is a continuing conundrum. In a case heard
      in the New South Wales Supreme Court in 1999, BT v Oei (1999) NSWSC 1082, the
      court held that a medical practitioner owed a duty of care to the sexual
      partner/s of a patient. Where there were signs/symptoms consistent with a
      diagnosis of HIV infection, the doctor had a duty to strongly advise the patient
      to be tested. Where the patient's results were positive, the doctor could not
      inform the partner/s directly; however, there was an obligation to counsel the
      patient to inform their partner/s of their HIV status, and to instruct the
      patient regarding the patient's own statutory responsibility to inform partner/s
      before engaging in sexual intercourse with them. A second case revolving around
      the issue of risk to third parties is the case of PD v Dr Nicholas Harvey & I Ors
      (2003) NSWSC 487, heard in the Supreme Court of NSW in 2003. The facts and the
      law discussed in this report are drawn from and summarised from the judgment of
      Cripps AJ.

PMID- 28762836
TI  - Post eLetter Solutions: Healthy Results for Improving Patient Communication
      Processes at the Royal Hobart Hospital.
AB  - The primary objective of the Australia Post eLetter project1 was to determine the
      feasibility of using the eLetter service with the Patient Administration System
      Appointment Scheduling Module to provide a fully automated mailing function that
      would eliminate the need for manual processing of mail delivery. Issues with
      timely delivery of letters throughout all outpatient sites at the Royal Hobart
      Hospital (RHH) have been identified as being mainly due to limited human
      resources being available to perform mailing duties and the like. This new
      desktop service enables staff to transmit data electronically in conjunction with
      the appointment software for large quantity mail postings to Australia Post via a
      secure line. Australia Post then validates the address, appends a barcode, prints
      the letter, envelopes it and inserts it into the mail distribution network in the
      state of the recipient. This article depicts the process that has eliminated the
      manual processing of a letter via the traditional Microsoft application,
      Wordmate, a system at RHH that was always difficult to use. With the introduction
      of eLetter, the RHH's Specialist Clinics have significantly improved the
      timeliness and quality of communication with patients as well as reducing
      administration tasks for staff.

PMID- 28762835
TI  - Semantic Interoperability, E-Health and Australian Health Statistics.
AB  - E-health implementation in Australia will depend upon interoperable computer
      systems to share information and data across the health sector. Semantic
      interoperability, which preserves the meaning of information and data when it is
      shared or re-purposed, is critical for safe clinical care, and also for any re
      use of the information or data for other purposes. One such re-use is for
      national health statistics. Usable statistics rely on comparable and consistent
      data, and current practice is to use agreed national data standards to achieve
      this. The standardisation and interoperability needed to support e-health should
      also provide strong support for national health statistics. This report discusses
      some of the semantic interoperability issues involved in moving from the current
      data supply process for national health statistics to an e-health-enabled future.

PMID- 28762837
TI  - The Royal Flying Doctor Service Flies to New Heights: The Journey of Health
      Information Management.
AB  - The Royal Flying Doctor Service (RFDS) of Australia was founded in 1928 by the
      Reverend John Flynn to deliver health services to the people of the Australian
      Outback. In this unique environment the RFDS Queensland Section provides both
      Primary Health Care and Aeromedical services to rural and remote communities
      throughout Queensland. It provides health services from a hub and spoke model and
      its clinicians work very closely with other health service providers, such as
      Queensland Heath, within the communities it visits. Currently, the RFDS' health
      records are both paper and electronic and clinicians duplicate much of patient
      information and data between RFDS and non-RFDS health records. Introduction of an
      off-the-shelf electronic medical record (EMR) would not meet the RFDS' clinical
      and organisational needs because of complexity, the multidisciplinary nature of
      the teams and the lack of communication technology in the communities the RFDS
      visits. This article defines the vision for a health information system designed
      to meet the requirements of the RFDS, and describes its implementation throughout
      RFDS Queensland using the PRINCE2 project management methodology.

PMID- 28762838
TI  - Healthcare Strategic Planning as Part of National and Regional Development in the
      Israeli Galilee: A Case Study of the Planning Process.
AB  - This article describes a systematic process of geographic and strategic planning
      for healthcare services as a part of a regional development plan in the Israeli
      Galilee. The planning process consisted of three stages: (a) assessment of needs,
      demand and existing resources; (b) prioritisation of initiatives; and (c)
      scheduling of theoretical priorities. For many years the region has suffered from
      inequities and inequalities regarding the availability and accessibility of a
      regional healthcare system, resulting in high mortality and morbidity rates and
      low quality of life. The aim of the healthcare strategic plan was to suggest
      initiatives and actions to be taken in order to improve healthcare provision and
      the health and wellbeing of local residents.

PMID- 28762839
TI  - New treatment options for lower respiratory tract infections.
AB  - INTRODUCTION: Community-acquired pneumonia (CAP) and acute exacerbation of
      chronic obstructive pulmonary disease (AECOPD) are among the most frequent lower
      respiratory tract infections (LRTIs). They represent an increased morbidity and
      mortality rate in adults. Areas covered: This review describes recent advances
      regarding solithromycin, zabofloxacin and delafoxacin antibacterial agents that
      have been recently developed for treatment of CAP and in AECOPD. All of them have
      been introduced into phase III clinical trials. We will be summarising chemical
      structures, pharmacokinetics, antibacterial efficacy and toxicity of these
      agents. The manuscript has been prepared based on available scientific
      publications. Expert opinion: Novel agents of known antimicrobial classes have
      been developed that demonstrate treatment options in CAP and in AECOPD.
      Antimicrobials discussed in this review showed bactericide effect against major
      respiratory tract pathogens. Each has multiple targets in bacteria, thus enabling
      them for more potency, even against strains exhibiting resistance to commonly
      used antibiotics. Solithromycin, delafloxacin and zabofloxcian demonstrate broad
      spectrum antibacterial activity together with other beneficial features like
      intracellular accumulation, anti-inflammatory effect and inhibition of biofilm
      production. These agents showed moderately severe or mild adverse events and
      demonstrated favourable tissue penetration. These features can make
      solithromycin, zabofloxacin and delafloxacin treatment options in LRTIs.

PMID- 28762840
TI  - Prevention in the elderly: A necessary priority for general practitioners.
AB  - Prevention is viewed as a key issue for general practice, yet there is a lack of
      evidence regarding general practitioners' interventions in both middle-aged and
      elderly people. This is despite the fact that recommendations and key indicators
      for monitoring the use of clinical preventive strategies aimed at these groups
      are available and that both the World Health Organization and European Commission
      endorse the importance of interventions for healthy and active ageing. This paper
      draws on two keynote presentations given at the 2015 autumn meeting of the
      European General Practice Research Network (EGPRN) in Edirne, Turkey (17-20
      October 2015). According to the EU2020 strategy, general practitioners should
      design and implement prevention services and programmes to promote healthy and
      active ageing. Their primary focus should be on interventions on multimorbid
      patients, either by improving prescribing and adherence to medical plans or by
      targeting to fall and frailty prevention and vaccination uptake.

PMID- 28762841
TI  - Haematuria is a marker for the severity of acute kidney injury but does not
      associate with thrombocytopenia in acute Puumala hantavirus infection.
AB  - BACKGROUND: Puumala hantavirus (PUUV) causes haemorrhagic fever with renal
      syndrome characterized by thrombocytopenia, capillary leakage and acute kidney
      injury (AKI) with proteinuria and haematuria. Although the typical histologic
      lesion is acute tubulointerstitial nephritis, the amount of glomerular
      proteinuria predicts the severity of upcoming AKI. Here, we studied the
      associations of haematuria and proteinuria with the severity of emerging AKI,
      thrombocytopenia and markers of coagulation and fibrinolysis in PUUV infection.
      METHODS: We examined 205 consecutive patients treated for serologically confirmed
      acute PUUV infection at Tampere University Hospital during 1997-2014. The
      patients were divided into three groups according to the combined positive result
      in urine haemoglobin and albumin dipstick tests: 0-2 + (n = 58), 3-4 + (n = 100)
      and 5-6 + (n = 47). RESULTS: The medians of maximum creatinine concentrations in
      the three groups were: 0-2 + 100 MUmol/L (range 52-1499), 3-4 + 204 MUmol/L
      (range 65-1071) and 5-6 + 361 MUmol/l (range 51-1285) (p < .001). The number of
      blood platelets (p = .069), and the levels of fibrinogen, prothrombin fragments
      F1 + 2 and d-dimer (p = .602, p = .113, p = .289, respectively) were not
      significantly different between the groups. When the amount of haematuria in the
      dipstick test was examined separately, no association with thrombocytopenia was
      detected (p = .307 between groups 0, 1+ and 2-3+). CONCLUSIONS: Combined positive
      result of haematuria and proteinuria in the dipstick test at hospital admission
      predicted the severity of upcoming AKI in acute PUUV infection. As haematuria was
      not associated with the severity of thrombocytopenia, it did not indicate
      increased bleeding tendency, but was rather a marker of acute kidney injury.

PMID- 28762842
TI  - Molecular bases of anorexia nervosa, bulimia nervosa and binge eating disorder:
      shedding light on the darkness.
AB  - Eating-disorders (EDs) consequences to human health are devastating, involving
      social, mental, emotional, physical and life-threatening aspects, concluding on
      impairment and death in cases of extreme anorexia nervosa. It also implies that
      people suffering an ED need to find psychiatric and psychological help as soon as
      possible to achieve a fully physical and emotional recovery. Unfortunately, to
      date, there is a crucial lack of efficient clinical treatment to these disorders.
      In this review, we present an overview concerning the actual pharmacological and
      psychological treatments, the knowledge of cells, circuits, neuropeptides,
      neuromodulators and hormones in the human brain- and other organs- underlying
      these disorders, the studies in animal models and, finally, the genetic
      approaches devoted to face this challenge. We will also discuss the need for new
      perspectives, avenues and strategies to be developed in order to pave the way to
      novel and more efficient therapeutics.

PMID- 28762843
TI  - Cost-effectiveness of 3-month paliperidone therapy for chronic schizophrenia in
      the Netherlands.
AB  - BACKGROUND: A new depot formulation of paliperidone has been developed that
      provides effective treatment for schizophrenia for 3 months (PP3M). It has been
      tested in phase-3 trials, but no data on its cost-effectiveness have been
      published. PURPOSE: To determine the cost-effectiveness of PP3M compared with
      once-monthly paliperidone (PP1M), haloperidol long-acting therapy (HAL-LAT),
      risperidone microspheres (RIS-LAT), and oral olanzapine (oral-OLZ) for treating
      chronic schizophrenia in The Netherlands. METHODS: A previous 1-year decision
      tree was adapted, based on local inputs supplemented with data from published
      literature. The primary analysis used DRG costs in 2016 euros from the insurer
      perspective, as derived from official lists. A micro-costing analysis was also
      conducted. For the costing scenario, official list prices were used. Clinical
      outcomes included relapses (treated as outpatients, requiring hospitalization,
      total), and quality-adjusted life-years (QALYs). Rates and utility scores were
      derived from the literature. Economic outcomes were the incremental cost/QALY
      gained or relapse-avoided. Model robustness was examined in scenario, 1-way, and
      probability sensitivity analyses. RESULTS: The expected cost was lowest with PP3M
      (8,781?), followed by PP1M (10,325?), HAL-LAT (11,278?), RIS-LAT (11,307?), and
      oral-OLZ (13,556?). PP3M had the fewest total relapses/patient (0.36, 0.94, 1.39,
      1.21, and 1.70, respectively), hospitalizations (0.11, 0.46, 0.40, 0.56, and
      0.57, respectively), emergency room visits (0.25, 0.48. 0.99, 0.65, and 1.14,
      respectively) and the most QALYs (0.847, 0.735, 0.709, 0.719, and 0.656,
      respectively). In both cost-effectiveness and cost-utility analyses, PP3M
      dominated all other drugs. Sensitivity analyses confirmed base case findings. In
      the costing analysis, total costs were, on average, 31.9% higher than DRGs.
      CONCLUSIONS: PP3M dominated all commonly used drugs. It is cost-effective for
      treating chronic schizophrenia in the Netherlands. Results were robust over a
      wide range of sensitivity analyses. For patients requiring a depot medication,
      such as those with adherence problems, PP3M appears to be a good alternative anti
      psychotic treatment.

PMID- 28762844
TI  - Correlation of Pancreatic Iron Overload Measured by T2*-Weighted Magnetic
      Resonance Imaging in Diabetic Patients with beta-Thalassemia Major.
AB  - Diabetes mellitus (DM) is one of the potential complications in patients with
      transfusion-dependent beta-thalassemia major (beta-TM). In this case-controlled
      study, we examined the pancreatic iron levels in outpatients with beta-TM. In
      this study, cases of patients with beta-TM and DM were gender- and age-matched
      with control subjects, who were non-diabetic and had normal blood glucose on
      standard oral glucose tolerance (OGTT) tests. One of four diagnoses [normal, pre
      diabetes, impaired glucose tolerance (IGT), DM] was made according to the
      American Diabetes Association (ADA) criteria. The T2*-weighted magnetic resonance
      imaging (T2*-weighted MRI) of the heart, liver, and pancreas was performed using
      a 1.5 Tesla scanner. The study enrolled 26 diabetic cases, 17 non-diabetic cases,
      and eight cases of IGT or pre-diabetes cases. The severity of pancreatic and
      cardiac iron siderosis was significantly different between the groups. We found a
      statistically significant difference at 5.6 ms in the T2*-weighted MRI values for
      the pancreas between patients with normal vs. abnormal glucose metabolism [p <
      0.009; odds ratio (OR): 11.2; 95% confidence interval (95% CI): 1.32-94.4)]. The
      receiver operating characteristic (ROC) curve for the 5.6 ms cutoff led to an
      area under the curve (AUC) of 0.69 (95% CI: 55.0-84.0; p < 0.02), with
      sensitivity and specificity of 94.0 and 42.0%, respectively. There was a moderate
      positive correlation between pancreatic and cardiac T2*-weighted MRI (r = 0.4; p
      < 0.001), and a weak correlation between the pancreas and the liver (r = 0.38; p
      < 0.005). To conclude, we have introduced a cutoff of 5.6 ms on T2*-weighted MRI
      of the pancreas for prediction of abnormal glucose metabolism in beta-TM
      patients.

PMID- 28762845
TI  - Decreased expression of interleukin-37 in the ectopic and eutopic endometria of
      patients with adenomyosis.
AB  - Previous studies have shown that alterations of cytokines might play a role in
      the pathogenesis of adenomyosis. This study aims to investigate the expression of
      interleukin-37 (IL-37), an anti-inflammatory cytokine, in the eutopic and ectopic
      endometria of patients with adenomyosis. Endometrial specimens were collected
      from 30 women with adenomyosis and 20 without adenomyosis. The gene and protein
      expression of IL-37 was measured using a quantitative real-time polymerase chain
      reaction and immunohistochemistry, respectively. Compared with the control
      endometria, the protein expression level and gene level of IL-37 was
      significantly lower in both the ectopic and eutopic endometria of patients with
      adenomyosis. The gene and protein expressions of IL-37 in ectopic endometria were
      lower than those in eutopic endometria of patients with adenomyosis. Our results
      suggest that there was a low level of IL-37 in the eutopic and ectopic endometria
      of patients with adenomyosis, and an abnormal inflammatory response might occur
      in the endometria of patients with adenomyosis.

PMID- 28762846
TI  - Biomimetic synthesis of proline-derivative templated mesoporous silica for
      increasing the brain distribution of diazepam and improving the pharmacodynamics
      of nimesulide.
AB  - Herein a new kind of proline-derivative templated mesoporous silica with curved
      channels (CMS) was biomimetically synthesized and applied as carrier to improve
      the drug dissolution and bioavailability of hydrophobic diazepam (DZP) and
      nimesulide (NMS). Drugs can be incorporated into CMS with high efficiency; during
      this process, they successfully transformed to amorphous phase. As a result, the
      dissolution rate of DZP and NMS was significantly improved. Biodistribution study
      confirmed that CMS converted DZP distribution in mice with the tendency of lung
      targeting and brain targeting. At 45 min postadministration, the concentrations
      of DZP in plasma, lung and brain were 8.57-fold, 124.94-fold and 19.55-fold
      higher from 1:3 DZP/CMS sample than that of pure DZP sample, respectively. At 90
      min postadministration, the content of DZP in brain was 62.31-fold higher for 1:3
      DZP/CMS sample than that of pure DZP. Besides, the anti-inflammatory and
      analgesic effects of 1:3 NMS/CMS were systematic evaluated using mouse ankle
      swelling test (MAST), mouse ear swelling test (MEST) and mouse writhing test
      (MWT). The results indicated that after incorporating into CMS, the therapeutic
      effects of NMS were obviously improved, and the inhibition rates of 1:3 NMS/CMS
      in all pharmacodynamics tests varied from 102.2% to 904.3%.

PMID- 28762847
TI  - Inhibition of NLRP3 inflammasome: a new protective mechanism of cinnamaldehyde in
      endotoxin poisoning of mice.
AB  - CONTEXT: Cinnamaldehyde (CA) has a protective effect in endotoxin poisoning of
      mice, but there is no direct evidence for the protective effect of CA through
      inhibition of NLRP3 inflammasome activation in endotoxin poisoning of mice.
      OBJECTIVE: We aimed to investigate the protective mechanism of CA in endotoxin
      poisoned mice through NLRP3 inflammasome. MATERIALS AND METHODS: First, we
      evaluated the anti-inflammatory effect of CA in phorbol-12-myristate acetate
      differentiated THP-1 cells through the NLRP3 inflammasome. Second, in a mouse
      model of lipopolysaccharide (LPS)-induced endotoxin poisoning, CA was
      administrated for 5 d (once a day) before the 15 mg/kg LPS challenge. Then, the
      levels of IL-1beta in serum were measured, and the effect of CA on the NLRP3
      inflammasome activation and the expression of cathepsin B and P2X7R proteins in
      lung were explored. RESULTS: In vitro, CA decreased the levels of p20, pro-IL
      1beta and IL-1beta in cell culture supernatants, as well as the expression of
      NLRP3 and IL-1beta mRNA in cells. In vivo, CA decreased IL-1beta production in
      serum. Furthermore, CA suppressed LPS-induced NLRP3, p20, Pro-IL-1beta, P2X7
      receptor (P2X7R) and cathepsin B protein expression in lung, as well as the
      expression of NLRP3 and IL-1beta mRNA. CONCLUSIONS: CA has a protective effect in
      the endotoxin poisoned mice through the inhibition of NLRP3 inflammasome
      activation. Furthermore, CA suppresses the NLRP3 inflammasome activation by
      inhibiting the expression of cathepsin B and P2X7R protein expression. CA can be
      considered as a potential therapeutic candidate for diseases involved in
      endotoxin poisoning such as sepsis.

PMID- 28762848
TI  - Healthcare resource utilization and costs for patients with pulmonary arterial
      hypertension: real-world documentation of functional class.
AB  - BACKGROUND AND AIMS: Pulmonary arterial hypertension (PAH) is a rare medical
      disease in which patients experience increased pulmonary vascular resistance
      (PVR) and pulmonary arterial pressure that can result in remodeling of the
      pulmonary vasculature and heart, and eventually lead to right heart failure and
      death. As PAH progresses, patients become unable to perform even routine daily
      tasks without severe shortness of breath (dyspnea), fatigue, dizziness, and
      fainting (syncope). Treatment strategies largely depend on assessment of an
      individual patient's WHO Functional Class. The aim of the present study was to
      determine whether PAH functional decline, as described by the WHO Functional
      class (FC), is associated with increased healthcare costs for patients. METHODS:
      Patients with a prescription for a FDA-approved treatment for PAH and a medical
      claim indicating chronic pulmonary heart disease or right heart catheterization
      were identified from an administrative claims database. Provider-reported data
      from prior authorization forms required for advanced PAH therapies and medical
      charts were examined for reported FC. Healthcare resource utilization and costs
      were the primary outcomes of interest. Costs were accounted in 2014 US dollars
      ($) from a healthcare payer perspective. RESULTS: Patients with a reported FC-IV
      were observed to have the worst outcomes; averaging significantly more inpatient
      admissions, longer average lengths of stay, and more emergency department visits
      than the other FC sub-groups, resulting in higher medical costs. CONCLUSIONS:
      Using administrative data to document disease severity, this study replicates and
      expands on findings obtained from the registry study; disease severity was
      associated with higher healthcare resource utilization and costs. Stakeholders'
      implications for patient management are discussed.

PMID- 28762850
TI  - NEHTA Terminology Analysts.

PMID- 28762849
TI  - First-Line Carboplatin, Pemetrexed, and Panitumumab in Patients with Advanced Non
      Squamous KRAS Wild Type (WT) Non-Small-Cell Lung Cancer (NSCLC).
AB  - BACKGROUND: We added panitumumab to standard combination chemotherapy as first
      line treatment for patients with advanced KRAS WT non-squamous NSCLC. METHODS:
      Patients received panitumumab 9 mg/kg IV, pemetrexed 500 mg/m2 IV, and
      carboplatin AUC = 6 IV every 21 days. After 6 cycles, maintenance therapy with
      panitumumab and pemetrexed was administered every 21 days until progressive
      disease or unacceptable toxicity. RESULTS: 29 of 66 patients (44%) had objective
      responses. The median TTP was 6 months; median overall survival (OS) was 17
      months. Panitumumab increased treatment-related toxicity, notably skin rash.
      CONCLUSIONS: The addition of panitumumab increased toxicity, and had no
      discernible impact on efficacy.

PMID- 28762851
TI  - Concentration of sulfated glycosaminoglycans in the mammary tissue of female rats
      with the aging and about hormonal influence.
AB  - It was to evaluate the concentration of sulfate glycosaminoglycans (GAG) in
      mammary tissue of the young and adult female rats and ovariectomized females rats
      after hormonal stimulation. For this purpose, 60 female rats were divided into
      six groups with 10 animals/each: nonovariectomized groups: G1 (5 months), and G2
      (15 months) and ovariectomized groups: OG (vehicle); EG: (estradiol, 7 days of
      treatment), PG (progesterone acetate, 23 days of treatment) and EPG: (estradiol
      (7 days of treatment) and next progesterone acetate (23 days of treatment).
      Twenty-four hours after the last treatment, all animals were euthanized, the
      mammary tissue removed, processed for biochemical evaluation and quantification
      of the GAG. The comparison between groups showed that the concentration dermatan
      sulfate (DS) G1 was lower compared to G2, OG, EG (p < .05) and G2 was lower
      compared to OG (p < .05), and OG was higher compared to EG, GP, EPG (p < .05);
      and heparan sulfate (HS) G1 was higher compared to G2 (p < .05), and G2 was
      higher compared to OG, EP, PG and EPG (p < .05). These changes in the
      extracellular matrix might explain, at least in part, hormonal influence about
      sulfated glycosaminoglycans in response to physiological state/age, and in
      response to hormonal treatment in the mammary tissues.

PMID- 28762852
TI  - Primary Management of Squamous Cell Carcinoma of the Anal Canal: A 30-year
      Community Hospital Experience.
AB  - We reviewed outcomes of 41 patients treated with curative-intent radiotherapy for
      anal canal carcinoma at a community hospital between 1985 and 2015. Twenty-six
      (63%) presented with stage I or II disease while 15 (37%) had stage III. Thirty
      seven received definitive chemoradiation and 4 radiotherapy alone. Thirteen
      (31.7%) received <=59.4Gy. Thirty-two (78%) were treated with 3-dimensional
      conformal radiotherapy while 9 (22%) received intensity-modulated radiotherapy.
      At 5 years, local control, regional control, freedom from distant metastasis,
      cause-specific survival, and overall survival were 80%, 98%, 88%, 77%, and 51%.
      Of those who received >59.4Gy, local control and overall survival were not
      improved.

PMID- 28762853
TI  - Carmel Cheney: Health Information Management Consultant.

PMID- 28762855
TI  - Marianne Carter: A Varied HIM Career in Retrospect.

PMID- 28762854
TI  - Lethal concentration of perfluoroisobutylene induces acute lung injury in mice
      mediated via cytokine storm, oxidative stress and apoptosis.
AB  - Perfluoroisobutylene (PFIB) is a highly toxic gas that targets the lungs. Low
      level inhalation of the gas can lead to acute lung injury (ALI), pulmonary edema
      and even death. No specific anti-PFIB drugs are currently available and the
      pathogenesis of PFIB-induced ALI is not fully understood. Early direct oxidative
      injury and a secondary hyper-inflammatory response are recognized as the primary
      mechanisms of PFIB-induced ALI. In the present study, our data demonstrate for
      the first time that a cytokine storm is associated with PFIB-induced ALI. Levels
      of 10 pro-inflammatory cytokines and one anti-inflammatory cytokine were
      significantly increased in lung tissues of PFIB-exposed mice. PFIB inhalation
      additionally led to significant oxidative stress in lung tissue. Inflammation
      associated CD11b+Ly6G+Ly6Cint neutrophils and CD11b+Ly6G-Ly6Chi monocytes were
      significantly increased in blood in association with PFIB-induced ALI. Bcl-2/Bax
      mediated lung cell apoptosis was significantly increased at 1 h, followed by a
      sustained decrease after 1 h, which was significant at 4-8 h in PFIB-exposed
      mice. This suppression of apoptosis is possibly associated with the Akt-signaling
      pathway.

PMID- 28762856
TI  - Exploring the diagnosis delay and ALS functional impairment at diagnosis as
      relevant criteria for clinical trial enrolment.
AB  - : Objectives were: i) to describe the phenotypic heterogeneity of incident
      amyotrophic lateral sclerosis (ALS) patients diagnosed in 2012 in French ALS
      centres; ii) to look at the associations between ALSFRS-R score and ALSFRS-R
      slope (DeltaFS) at time of diagnosis with diagnosis delay, ALS phenotypes and
      Airlie House diagnosis criteria (AHDC); iii) to describe the rate of progression
      on DeltaFS, according to diagnosis delay. METHODS: Incident ALS cases diagnosed
      in French ALS centres were included. The rate of progression was evaluated as
      follows: DeltaFS = (48 - ALSFRS-R at time of diagnosis)/duration from onset to
      diagnosis (months). Fast and slow progressors were defined by DeltaFS >1 and
      <0.5, respectively. RESULTS: At time of diagnosis, 476 patients were classified
      into eight phenotypes: bulbar (33.0%), spinal lumbar (28.2%), spinal cervical
      (23.1%), flail leg (4.4%), ALS/FTD (4.2%), possible flail arm (4.0%), respiratory
      (2.1%), dropped-head (1.0%). Median DeltaFS (n = 358/476) was 1.0 [0.5-2.0].
      DeltaFS was associated with AHDC (p = 0.009), but not with clinical phenotype (p
      = 0.902). Stratification on diagnosis delay (<12 months or >=18 months) allowed
      to differentiate fast progressors from slow progressors. CONCLUSION: At time of
      inclusion in therapeutic trial closed to diagnosis, DeltaFS or diagnosis delay
      may discriminate the rate of progression.

PMID- 28762857
TI  - The Changing Health Information Service (HIS) Work Environment.

PMID- 28762858
TI  - Influence of polyvinylpyrrolidone, microcrystalline cellulose and colloidal
      silicon dioxide on technological characteristics of a high-dose Petiveria
      alliacea tablet.
AB  - PURPOSE: Petiveria alliacea L. (Phytolaccaceae) is a perennial shrub used by its
      immunomodulatory, anticancerogenic and anti-inflammatory properties. This study
      determined the influence of polyvinylpyrrolidone (PVP), colloidal silicon dioxide
      (CSD) and microcrystalline cellulose (MC) on the technological characteristic of
      a high-dose P. alliacea tablet prepared by the wet granulation method.
      METHODOLOGY: The botanical and pharmacognostic analysis of the plant material was
      firstly performed, followed by a 23 factorial design considering three factors at
      two levels: (a) the binder (PVP) incorporated in formulation at 10% and 15%
      (w/w); (b) the compacting agent (CSD) added at 10% and 15% (w/w) and; (c) the
      diluent (MC) included at 7.33% and 12.46% (w/w). The analysis of pharmaceutical
      performance and the accelerated and long-term stability of the best prototype
      were also completed. RESULT AND DISCUSSION: The binder, compacting agent and the
      interaction binder/diluent had a significant impact on breaking force of high
      dose P. alliacea tablet. The optimum formula was found to contain 15% (w/w) of
      CSD, 7.33% (w/w) of MC and 10% (w/w) of PVP. At these conditions, the tablet
      shows a breaking force of 77.96 N, a friability of 0.39%, a total phenol content
      of 1.30 mg/tablet and a maximum disintegration time of 6 min. CONCLUSIONS: The
      use of adequate amounts of PVP, MC and CSD as per the factorial design allowed
      the preparation of a tablet suitable for administration, despite the
      inappropriate flow and compressibility properties of the P. alliacea powder.

PMID- 28762860
TI  - Intensive strength and balance training with the Kinect console (Xbox 360) in a
      patient with CMT1A.
AB  - BACKGROUND: Effective drugs for type 1A Charcot-Marie-Tooth (CMT1A) disease are
      not available. Various forms of moderate exercise are beneficial, but few data
      are available on the effectiveness of exercise in CMT1A children. AIM: To
      investigate the feasibility and effectiveness of exercises to improve ankle
      strength and limb function in a child with CMT1A. SETTING: Outpatient clinic.
      POPULATION: Nine-year-old boy with CMT1A. METHODS: The rehabilitation program
      consisted of ankle exercises and Kinect videogame-directed physical activities
      (using an Xbox 360 console/movement sensor) that aimed to improve balance and
      limb strength. The program was given 3 times a week for 5 weeks. The child was
      assessed at baseline, after 5 weeks, and 3 and 6 months after. RESULTS: By the
      end of follow-up, child balance and endurance had improved, but ankle strength
      did not. CONCLUSIONS: The encouraging results for balance and endurance justify
      further studies on videogame-directed activities in CMT1A children/adolescents.

PMID- 28762859
TI  - Social Participation and Navigation (SPAN): Description and usability of app
      based coaching intervention for adolescents with TBI.
AB  - BACKGROUND: Adolescents with brain injury (BI) often experience impairment in
      participation, which is an important predictor of outcomes. OBJECTIVE: Describe
      the Social Participation and Navigation (SPAN) program, and report participant
      feedback and preliminary outcomes. METHOD: Four adolescents and four coaches
      participated. SPAN included a mobile app, online didactic information, and peer
      coaching. Adolescents met weekly with coaches via video-conference, developed
      participation goals, and plans to achieve goals. Social and behavioral
      functioning before and after was assessed, and feedback about SPAN was collected.
      RESULTS: SPAN was well received. Participants used the app to define and achieve
      goals. Medium to large effect sizes were found on adolescent self-reported
      measures, with negligible effects on parent-report measures. Positive and
      critical feedback is described. CONCLUSIONS: Findings support the usability of
      SPAN, which has the potential to improve social participation of adolescents with
      a history of TBI through an innovative use of technology and peer coaching.

PMID- 28762861
TI  - MiR-1298 affects cell proliferation and apoptosis in C6 cells by targeting SET
      domain containing 7.
AB  - Our previous high-throughput sequencing indicated that rno-miR-1298 was down
      regulated in ischemia-reperfusion model of rat. However, little is known about
      the function and molecular mechanism of rno-miR-1298 in rat tumor cell. In this
      study, rno-miR-1298 was detected to be significantly down-regulated in rat tumor
      C6 cells. Moreover, overexpression of rno-miR-1298 obviously inhibited the
      proliferation and induced apoptosis in C6 cells. SET domain containing 7 (SETD 7)
      was identified to be a target of rno-miR-1298 using bioinformatics and luciferase
      reporter assays. Overexpression of rno-miR-1298 markedly reduced the expression
      of SETD 7 at protein level. Knockdown of SETD 7 also suppressed proliferation and
      promoted apoptosis in C6 cells. It was indicated that rno-miR-1298 affected cell
      proliferation and apoptosis of rat tumor cells by targeting SETD 7. Thus, the
      newly identified miR-1298/SETD 7 expands the elaboration of the mechanisms of the
      development and progression of tumors and may provide therapeutic target for
      tumors of nervous system.

PMID- 28762862
TI  - A clinician's guide to ADHD treatment options.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental
      condition of children and adolescents that often persists into adulthood. Primary
      care physicians are commonly the first to diagnosis ADHD and initiate a treatment
      plan with the patient. Guidelines recommend psychostimulant treatment as a first
      line therapy in the management plan because it has a substantial impact on
      alleviating the core symptoms of ADHD. The recent development of a variety of
      methylphenidate and amphetamine formulations provides many options to meet
      individual patient lifestyle needs. Liquid, chewable, sprinkled capsule, wearable
      patch, and orally disintegrating tablet formulations are currently available for
      patients who may be noncompliant with or have difficulty swallowing traditional
      pills. This review provides a resource for physicians to identify the stimulant
      delivery formulation that best suits the patient. Formulations in development are
      also discussed.

PMID- 28762864
TI  - Progesterone hydroxylation by cytochromes P450 2C and 3A enzymes in marmoset
      liver microsomes.
AB  - 1. Common marmosets (Callithrix jacchus) are potentially useful nonhuman primate
      models for preclinical drug metabolism studies. However, the roles of marmoset
      cytochrome P450 (P450) isoforms in the oxidation of endobiotic progesterone have
      not been fully investigated. In this study, the roles of marmoset P450 isoforms
      in progesterone hydroxylation were extensively determined. 2. The activities of
      liver microsomes from individual marmosets with respect to progesterone
      21/17alpha- and 16alpha/6beta-hydroxylation were significantly correlated with
      those for flurbiprofen 4-hydroxylation and midazolam 1'-hydroxylation,
      respectively, as similar correlations have been found in humans. Anti-P450 2 C
      and 3 A antibodies suppressed progesterone 21/17alpha- and 16alpha/6beta
      hydroxylation, respectively, in marmoset liver microsomes. 3. Recombinant
      marmoset P450 2C58 and 2C19 catalyzed progesterone to form 21-hydroxyprogesterone
      and 16alpha-hydroxyprogesterone, respectively, as major products with high
      maximum velocity/Km values of 0.53 and 0.089 mL/min/nmol, respectively.
      Recombinant marmoset P450 3A4/90 oxidized progesterone to form 6beta
      hydroxyprogesterone as a major product with homotropic cooperativity (>1 of Hill
      coefficients). 4. These results indicate that the overall activities and roles of
      liver microsomal P450 enzymes in marmoset livers are similar to those in humans,
      especially for progesterone 21/17alpha- and 16alpha/6beta-hydroxylation by
      marmoset P450 2 C and 3 A enzymes, respectively, suggesting important roles for
      these P450 enzymes in the metabolism of endobiotics in marmosets.

PMID- 28762863
TI  - Dendritic cells maturated by co-culturing with HIV-1 latently infected Jurkat T
      cells or stimulating with AIDS-associated pathogens secrete TNF-alpha to
      reactivate HIV-1 from latency.
AB  - Elucidation of mechanisms underlying the establishment, maintenance of and
      reactivation from HIV-1 latency is essential for the development of therapeutic
      strategies aimed at eliminating HIV-1 reservoirs. Microbial translocation, as a
      consequence of HIV-1-induced deterioration of host immune system, is known to
      result in a systemic immune activation and transient outbursts of HIV-1 viremia
      in chronic HIV-1 infection. How these microbes cause the robust HIV-1
      reactivation remains elusive. Dendritic cells (DCs) have previously been shown to
      reactivate HIV-1 from latency; however, the precise role of DCs in reactivating
      HIV-1 from latently infected T-cell remains obscure. In this study, by using HIV
      1 latently infected Jurkat T cells, we demonstrated that AIDS-associated
      pathogens as represented by Mycobacterium bovis (M. bovis) Bacillus Calmette
      Guerin (BCG) and bacterial component lipopolysaccharide (LPS) were unable to
      directly reactivate HIV-1 from Jurkat T cells; instead, they mature DCs to
      secrete TNF-alpha to accomplish this goal. Moreover, we found that HIV-1 latently
      infected Jurkat T cells could also mature DCs and enhance their TNF-alpha
      production during co-culture in a CD40-CD40L-signaling-dependent manner. This in
      turn led to viral reactivation from Jurkat T cells. Our results reveal how DCs
      help AIDS-associated pathogens to trigger HIV-1 reactivation from latency.

PMID- 28762865
TI  - Chronic wasting disease prion infection of differentiated neurospheres.
AB  - A possible strategy to develop more diverse cell culture systems permissive to
      infection with naturally occurring prions is to exploit culture of neurospheres
      from transgenic mice expressing the normal prion protein (PrP) of the native host
      species. Accordingly, we developed differentiated neurosphere cultures from the
      cervid PrP-expressing mice to investigate whether this in vitro system would
      support replication of non-adapted cervid-origin chronic wasting disease (CWD)
      prions. Here we report the successful amplification of disease-associated PrP in
      differentiated neurosphere cultures within 3 weeks after exposure to CWD prions
      from both white-tailed deer or elk. This neurosphere culture system provides a
      new in vitro tool that can be used to assess non-adapted CWD prion propagation
      and transmission.

PMID- 28762866
TI  - In Vitro Bioactivity of One- and Two-Dimensional Nanoparticle-Incorporated Bone
      Tissue Engineering Scaffolds.
AB  - This study investigates the effect of incorporation of one- or two-dimensional
      nanoparticles with distinct composition and morphology on the bioactivity of
      biodegradable, biocompatible polymer matrices. 0.2 wt% multiwalled carbon
      nanotubes, multiwalled graphene nanoribbons, graphene oxide nanoplatelets
      (GONPs), molybdenum disulfide nanoplatelets (MSNPs), or tungsten disulfide
      nanotubes (WSNTs) were uniformly dispersed in poly(lactic-co-glycolic acid)
      (PLGA) polymer. PLGA or nanoparticle-incorporated PLGA were then incubated with
      simulated body fluid (SBF) under physiological conditions for 1, 3, 7, or 14
      days. Apatite collection on control and incorporated scaffolds was assessed. All
      groups showed apatite precipitate on the surface after 1 day of SBF incubation.
      After 14 days of SBF incubation, scaffolds incorporated with GONPs, MSNPs, or
      WSNTs showed significantly higher phosphate accumulation compared to PLGA
      scaffolds. Scaffolds incorporated with GONPs, MSNPs, or WSNTs should be studied
      in vivo to further investigate potential bioactivity, leading to enhanced
      integration and tissue repair at the bone-implant interface.

PMID- 28762867
TI  - Deficient Data Dissemination Does Damage.

PMID- 28762869
TI  - * Endocultivation of Scaffolds with Recombinant Human Bone Morphogenetic Protein
      2 and VEGF165 in the Omentum Majus in a Rabbit Model.
AB  - The reconstruction of defects in the mandible are still challenging. Despite
      several adequate microvascular bone reconstruction techniques, there is a need
      for ectopic bone endocultivation without drawbacks by donor-site morbidity. The
      omentum majus is described as a good vascularized fleece with undifferentiated
      cells with potential for bone culturing. In the omentum majus of six rabbits, two
      hydroxyapatite blocks were incorporated for 12 weeks each. The blocks were
      prepared with recombinant human bone morphogenetic protein-2 (rhBMP-2) or VEGF165
      + rhBMP-2 and wrapped into the omentum. For ectopic bone endocultivation
      observation computed tomography (CT) scans were performed, and fluorescence
      markers were applied. After harvesting the block, histological sections were
      performed with hematoxylin and eosin and toluidine blue staining. In the CT
      scans, the Hounsfield units of the blocks increased within the trail. In some
      sections, new bone formation was observed within the hydroxyapatite blocks,
      however, the histological staining showed soft-tissue invasion only, no gross
      bone formation was observed. The ectopic bone endocultivation in the omentum
      majus is technically a good approach. An adequate mixture of osteoinductive
      proteins is still missing.

PMID- 28762870
TI  - Increased Sleep Need and Reduction of Tuberomammillary Histamine Neurons after
      Rodent Traumatic Brain Injury.
AB  - Although sleep-wake disturbances are prevalent and well described after traumatic
      brain injury, their pathophysiology remains unclear, most likely because human
      traumatic brain injury is a highly heterogeneous entity that makes the systematic
      study of sleep-wake disturbances in relation to trauma-induced histological
      changes a challenging task. Despite increasing interest, specific and effective
      treatment strategies for post-traumatic sleep-wake disturbances are still
      missing. With the present work, therefore, we aimed at studying acute and chronic
      sleep-wake disturbances by electrophysiological means, and at assessing their
      histological correlates after closed diffuse traumatic brain injury in rats with
      the ultimate goal of generating a model of post-traumatic sleep-wake disturbances
      and associated histopathological findings that accurately represents the human
      condition. We assessed sleep-wake behavior by means of standard
      electrophysiological recordings before and 1, 7, and 28 days after sham or
      traumatic brain injury procedures. Sleep-wake findings were then correlated to
      immunohistochemically labeled and stereologically quantified neuronal arousal
      systems. Compared with control animals, we found that closed diffuse traumatic
      brain injury caused increased sleep need one month after trauma, and sleep was
      more consolidated. As histological correlate, we found a reduced number of
      histamine immunoreactive cells in the tuberomammillary nucleus, potentially
      related to increased neuroinflammation. Monoaminergic and hypocretinergic
      neurotransmitter systems in the hypothalamus and rostral brainstem were not
      affected, however. These results suggest that our rat traumatic brain injury
      model reflects human post-traumatic sleep-wake disturbances and associated
      histopathological findings very accurately, thus providing a study platform for
      novel treatment strategies for affected patients.

PMID- 28762871
TI  - Differences between leisure-time physical activity, health-related quality of
      life and life satisfaction: Al Ritmo de las Comunidades, a natural experiment
      from Colombia.
AB  - Physical inactivity is one of the major public health problems worldwide.
      Community-based interventions have been pointed out as a promising strategy to
      increase physical activity (PA) levels and impact population health. Recreovia is
      a community program with a potential to promote PA. There is growing evidence for
      two benefits derived from the practice of PA: an increased perception of health
      related quality of life (HRQoL) and life satisfaction (LS). The purpose of this
      study was to assess differences between leisure-time PA and perceptions of both
      HRQoL and LS, as well as to assess differences between perceptions of both HRQoL
      and LS for Recreovia and non-Recreovia participants. Data were obtained using the
      baseline cross-sectional survey of 1533 participants (501 belonged to the
      intervention group) as part of the natural experiment Al Ritmo de las
      Comunidades. HRQoL was measured with the European Organization for Research and
      Treatment of Cancer 30-item questionnaire, LS was measured with Questions on Life
      Satisfaction Scale, and self-reported minutes of leisure-time PA were measured
      with the long version of the International Physical Activity Questionnaire. The
      mean age of participants was 41.7 years (standard deviation (SD) = 16.3). The
      participants had a good overall HRQoL and LS. The mean minutes of leisure-time PA
      were 158.1 min (SD = 230.2) a week. Results showed that those participants who
      reported higher leisure-time PA levels also reported a significantly higher LS (M
      = 41.9, SD = 35.0) relative to participants with lower levels (M = 37.6, SD =
      34.2, t(1532) = -2.36, p < 0.01). There were no statistical differences in the
      perception of HRQoL and leisure-time PA ( t(1532) = -1.03, p = 0.30), although
      active people had higher scores. Both HRQoL and LS scores were higher in
      individuals who were participating in Recreovia ( p < 0.001). Higher LS scores
      were found in the group with higher leisure-time PA, while HRQoL showed no
      differences. Better psychological well-being indices were found in the Recreovia
      group.

PMID- 28762868
TI  - Investigating intracellular persistence of Staphylococcus aureus within a murine
      alveolar macrophage cell line.
AB  - OBJECTIVE: Staphylococcus aureus is a particularly difficult pathogen to
      eradicate from the respiratory tract. Previous studies have highlighted the
      intracellular capacity of S.aureus in several phagocytic and non-phagocytic
      cells. The aim of this study was to define S.aureus interaction within a murine
      alveolar macrophage cell line. METHODS: Cell line MH-S was infected with Newman
      strain. Molecular mechanisms involved in phagocytosis were explored. To assess
      whether S.aureus survives intracellularly quantitative (gentamicin protection
      assays and bacterial plating) and qualitative analysis (immunofluorescence
      microscopy) were performed. Bacterial colocalization with different markers of
      the endocytic pathway was examined to characterize its intracellular trafficking.
      RESULTS: We found that S.aureus uptake requires host actin polymerization,
      microtubule assembly and activation of phosphatidylinositol 3-kinase signaling.
      Time course experiments showed that Newman strain was able to persist within
      macrophages at least until 28.5 h post infection. We observed that intracellular
      bacteria are located inside an acidic subcellular compartment, which co-localizes
      with the late endosome/lysosome markers Lamp-1, Rab7 and RILP. Colocalization
      counts with TMR-dextran might reflect a balance between bacterial killing and
      intracellular survival. CONCLUSIONS: This study indicates that S.aureus persists
      and replicates inside murine alveolar macrophages, representing a privileged
      niche that can potentially offer protection from antimicrobial activity and
      immunological host defense mechanisms.

PMID- 28762872
TI  - The role of the SMART and WHIM in behavioural assessment of disorders of
      consciousness: clinical utility and scope for a symbiotic relationship.
AB  - As the prevalence and incidence of disorders of consciousness (DoC) increase,
      researchers and clinicians are tasked with developing best practice assessment
      techniques. Neurobehavioural assessment remains the most clinically available
      method of measuring consciousness. Neuroimaging and other physiological
      measurements are demonstrating promise in supporting this assessment but many of
      these techniques require further research and are not widely available in sub
      acute and long-term care settings. No study to date has explored in-depth
      complementary use of multiple neurobehavioural assessments in aiding beside
      assessment of consciousness. This paper describes and proposes complementary use
      of two commonly used standardised neurobehavioural assessments. The Sensory
      Modality Assessment and Rehabilitation Technique (SMART) and the Wessex Head
      Injury Matrix (WHIM) both have specific aims and play an important role in
      behavioural assessment across the care continuum. This paper proposes that when
      used together appropriately these two assessments promote best practice and
      strengthen behavioural assessment of consciousness by providing increased
      opportunities to capture awareness. Further research into use of more than one
      neurobehavioural tool is highlighted as an important area of inquiry for this
      heterogeneous population not only in clinical practice but also in research.

PMID- 28762873
TI  - Management of hot flushes in UK breast cancer patients: clinician and patient
      perspectives.
AB  - INTRODUCTION: Menopausal problems are among the most prevalent and distressing
      problems following breast cancer treatment, with 70% women experiencing hot
      flushes and night sweats (HFNS). A working party was set up to support the
      development of new research into the management of these problems. METHODS: We
      conducted surveys to explore the need as perceived by women with breast cancer
      and establish current UK management practices. A patient survey was conducted
      through a charity, Breast Cancer Care, and a health professional survey via the
      UK Breast Intergroup. The HFNS Problem Rating Scale was used, as well as specific
      questions addressing the aims of the study. RESULTS: Six hundred and sixty-five
      patients responded and 185 health professionals. Twenty-eight percent women had
      considered stopping adjuvant endocrine treatment because of HFNS, yet 34% had
      never been asked about HFNS by any health professional. The most commonly offered
      interventions were SSRIs, such as venlafaxine, yet only 25% patients had been
      offered these drugs. Cognitive behavioural therapy was rarely suggested (2%)
      despite good evidence. DISCUSSION: This study shows a lack of coherence in the
      management of HFNS in breast cancer survivors, which may lead to reduced
      adherence to adjuvant therapy. There is an urgent need to develop guidelines to
      support management of HFNS after breast cancer.

PMID- 28762874
TI  - Reactivation of hyperglycemia-induced hypocretin (HCRT) gene silencing by N
      acetyl-d-mannosamine in the orexin neurons derived from human iPS cells.
AB  - Orexin neurons regulate critical brain activities for controlling sleep, eating,
      emotions, and metabolism, and impaired orexin neuron function results in several
      neurologic disorders. Therefore, restoring normal orexin function and
      understanding the mechanisms of loss or impairment of orexin neurons represent
      important goals. As a step toward that end, we generated human orexin neurons
      from induced pluripotent stem cells (hiPSCs) by treatment with N-acetyl-d
      mannosamine (ManNAc) and its derivatives. The generation of orexin neurons was
      associated with DNA hypomethylation, histone H3/H4 hyperacetylation, and hypo-O
      GlcNAcylation on the HCRT gene locus, and, thereby, the treatment of inhibitors
      of SIRT1 and OGT were effective at inducing orexin neurons from hiPSCs. The
      prolonged exposure of orexin neurons to high glucose in culture caused
      irreversible silencing of the HCRT gene, which was characterized by H3/H4
      hypoacetylation and hyper-O-GlcNAcylation. The DNA hypomethylation status, once
      established in orexin neurogenesis, was maintained in the HCRT-silenced orexin
      neurons, indicating that histone modifications, but not DNA methylation, were
      responsible for the HCRT silencing. Thus, the epigenetic status of the HCRT gene
      is unique to the hyperglycemia-induced silencing. Intriguingly, treatment of
      ManNAc and its derivatives reactivated HCRT gene expression, while inhibitors
      SIRT1 and the OGT did not. The present study revealed that the HCRT gene was
      silenced by the hyperglycemia condition, and ManNAc and its derivatives were
      useful for restoring the orexin neurons.

PMID- 28762875
TI  - Edwardsiella tarda-induced miRNAs in a teleost host: Global profile and role in
      bacterial infection as revealed by integrative miRNA-mRNA analysis.

PMID- 28762876
TI  - Constraints on Stance-Phase Force Production during Overground Walking in Persons
      with Chronic Incomplete Spinal Cord Injury.
AB  - Persons with incomplete spinal cord injury (iSCI) face ongoing struggles with
      walking, including reduced speed and increased reliance on assistive devices
      (ADs). The forces underlying body weight support and gait, as measured by ground
      reaction forces (GRFs), are likely altered after iSCI because of weakness and AD
      dependence but have not been studied. The purpose of this study was to examine
      GRF production during overground walking after iSCI, because greater insight into
      GRF constraints is important for refining therapeutic interventions. Because of
      reduced and discoordinated motor output after iSCI, we hypothesized that persons
      with iSCI would exert smaller GRFs and altered GRF modifications to increased
      cadence compared with able-bodied (AB) persons, especially when using an AD.
      Fifteen persons with chronic iSCI, stratified into no AD (n = 7) and AD (n = 8)
      groups, walked across an instrumented walkway at self-selected and fast (115%
      self-selected) cadences. Fifteen age-matched AB controls walked at their own
      cadences and iSCI-matched conditions (cadence and AD). Results showed fore-aft
      GRFs are reduced in persons with iSCI compared with AB controls, with reductions
      greatest in persons dependent on an AD. When controlling for cadence and AD,
      propulsive forces were still lower in persons with iSCI. Compared with AB
      controls, persons with iSCI demonstrated altered GRF modifications to increased
      cadence. Persons with iSCI exhibit different stance-phase forces compared with AB
      controls, which are impacted further by AD use and slower walking speed.
      Minimizing AD use and/or providing propulsive biofeedback during walking could
      enhance GRF production after iSCI.

PMID- 28762877
TI  - Rituximab in multiple sclerosis: Frequency and clinical relevance of anti-drug
      antibodies.
AB  - BACKGROUND: Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting
      antibody increasingly used off-label in multiple sclerosis (MS). The clinical
      relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown.
      OBJECTIVE: To determine frequency of ADA in relation to B-cell counts, allergic
      reactions and clinical efficacy in a large cohort of MS-treated patients.
      METHODS: Cross-sectional study with collection of serum samples from 339 MS
      patients immediately before a scheduled rituximab infusion. ADAs were detected
      using an in-house-validated electrochemiluminescent immunoassay and a commercial
      enzyme-linked immunosorbent assay (ELISA) to compare methods. Data on patient
      demographics and clinical outcomes were retrieved from the Swedish MS Registry
      and patient records. RESULTS: ADAs were detected in 37% of relapsing-remitting MS
      and 26% in progressive forms of MS. Presence of ADAs decreased with increasing
      number of rituximab infusions. There was a significant association between both
      presence and titres of ADAs and incomplete B-cell depletion, but not with
      infusion/adverse reactions or clinical outcomes at the group level. Only five
      patients terminated rituximab during follow-up, four of which were ADA positive.
      CONCLUSION: Rituximab treatment is associated with a high degree of ADAs, which
      correlates with efficacy of B-cell depletion; however, the clinical relevance of
      ADAs remains uncertain.

PMID- 28762878
TI  - Long-acting statin for aneurysmal subarachnoid hemorrhage: A randomized, double
      blind, placebo-controlled trial.
AB  - Statins have pleiotropic effects that are considered beneficial in preventing
      cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid
      hemorrhage (aSAH). Many studies using statins have been performed but failed to
      show remarkable effects. We hypothesized that a long-acting statin would be more
      effective, due to a longer half-life and stronger pleiotropic effects. Patients
      with aSAH were randomly assigned to a pitavastatin group (4 mg daily; n = 54) and
      a placebo group ( n = 54) after repair of a ruptured aneurysm. The primary
      efficacy end point was vasospasm-related delayed ischemic neurological deficits
      (DIND), and the secondary end points were cerebral vasospasm evaluated by digital
      subtraction angiography (DSA), vasospasm-related new cerebral infarctions, and
      outcome at three months. Severe cerebral vasospasms on DSA were statistically
      fewer in the pitavastatin group than in the placebo group (14.8% vs. 33.3%; odds
      ratio, 0.32; 95% confidence interval, 0.11-0.87, p = 0.042); however, the
      occurrence of DIND and new infarctions and outcome showed no statistically
      significant differences between the groups. The present study is the first to
      prove the definite, statin-induced amelioration of cerebral vasospasm on DSA.
      However, administration of any type of statin at the acute phase of aSAH is not
      recommended.

PMID- 28762879
TI  - Successful Goal-Directed Memory Suppression is Associated With Increased Inter
      Hemispheric Coordination Between Right and Left Frontoparietal Control Networks.
AB  - The neural basis of suppressing conscious access to one's own memories has
      recently received considerable attention, with several studies suggesting this
      process engages frontal-parietal cognitive control regions. However, researchers
      to date have not examined the way right and left hemisphere cognitive control
      networks coordinate with one another to accomplish this. We had 48 participants
      (25 female) complete a Think/No Think (T/NT) task for memories of emotionally
      unpleasant visual scenes while undergoing functional magnetic resonance imaging.
      We used generalized psychophysiologic interaction analyses to examine functional
      connectivity between right and left hemisphere frontal-parietal regions during
      memory suppression. Participants who were better at memory suppression, as
      assessed by greater numbers of forgotten memories in the NT than T conditions,
      also showed greater functional connectivity between multiple right and left
      hemisphere control regions. This suggests that individual differences in memory
      suppression ability may be partially explained by differences in task-specific
      inter-hemispheric coordination.

PMID- 28762880
TI  - The Structure of Intelligence in Childhood: Age and Socio-Familiar Impact on
      Cognitive Differentiation.
AB  - The Cattell-Horn-Carroll theory is the principal model at present to define and
      assess intelligence. However, several authors have suggested that the structure
      of intelligence is not stable throughout life. For example, children tend to
      present a general ability, which is invested in the development of specific and
      differentiated abilities during adolescence, reflecting the effect of schooling,
      experiences, and interests. In this study, an intelligence nine subtests battery
      was applied to a sample of 470 5-, 7-, and 9-year-old Portuguese children, from
      public and private basic schools. Two structure models have been tested, one
      assuming a global general factor loading by the nine subtests, and a second one
      formed by two factors integrating the verbal and non-verbal subtests. The results
      provide evidence of better fit of the second model where intelligence performance
      is organized in traditional verbal and non-verbal factors. This structure model
      is confirmed taking 5-, 7-, and 9-year-old children subgroups. A posterior path
      analysis verifies the impact of socio-familial variables in both factors. More
      than parents' educational levels and professional status, the results suggest the
      sibship size appears as more relevant on explanation of children cognitive
      performance.

PMID- 28762881
TI  - Porcine Ischemic Wound-Healing Model for Preclinical Testing of Degradable
      Biomaterials.
AB  - Impaired wound healing that mimics chronic human skin pathologies is difficult to
      achieve in current animal models, hindering testing and development of new
      therapeutic biomaterials that promote wound healing. In this article, we describe
      a refinement and simplification of the porcine ischemic wound model that
      increases the size and number of experimental sites per animal. By comparing
      three flap geometries, we adopted a superior configuration (15 * 10 cm) that
      enabled testing of twenty 1 cm2 wounds in each animal: 8 total ischemic wounds
      within 4 bipedicle flaps and 12 nonischemic wounds. The ischemic wounds exhibited
      impaired skin perfusion for ~1 week. To demonstrate the utility of the model for
      comparative testing of tissue regenerative biomaterials, we evaluated the healing
      process in wounds implanted with highly porous poly (thioketal) urethane (PTK-UR)
      scaffolds that were fabricated through reaction of reactive oxygen species (ROS)
      cleavable PTK macrodiols with isocyanates. PTK-lysine triisocyanate (LTI)
      scaffolds degraded significantly in vitro under both oxidative and hydrolytic
      conditions whereas PTK-hexamethylene diisocyanate trimer (HDIt) scaffolds were
      resistant to hydrolytic breakdown and degraded exclusively through an ROS
      dependent mechanism. Upon placement into porcine wounds, both types of PTK-UR
      materials fostered new tissue ingrowth over 10 days in both ischemic and
      nonischemic tissue. However, wound perfusion, tissue infiltration and the
      abundance of pro-regenerative, M2-polarized macrophages were markedly lower in
      ischemic wounds independent of scaffold type. The PTK-LTI implants significantly
      improved tissue infiltration and perfusion compared with analogous PTK-HDIt
      scaffolds in ischemic wounds. Both LTI and HDIt-based PTK-UR implants enhanced M2
      macrophage activity, and these cells were selectively localized at the
      scaffold/tissue interface. In sum, this modified porcine wound-healing model
      decreased animal usage, simplified procedures, and permitted a more robust
      evaluation of tissue engineering materials in preclinical wound healing research.
      Deployment of the model for a relevant biomaterial comparison yielded results
      that support the use of the PTK-LTI over the PTK-HDIt scaffold formulation for
      future advanced therapeutic studies.

PMID- 28762883
TI  - * A Paradigm for the Evaluation of Tissue-Engineering Biomaterials and Templates.
AB  - Procedures for the evaluation of tissue-engineering processes, including those
      used for the testing of the relevant biomaterials, have not been developed in a
      logical manner. This perspectives paper discusses the limitations of testing
      regimes and recommends a very different approach. The main emphasis is on the
      existing methods for assessing the biological safety of these biomaterials,
      which, it is suggested, are irrelevant for evaluating materials that are intended
      to facilitate the generation of new tissue. An algorithm is proposed that sets
      out the pathway from materials design and characterization through to the
      production of a file that sets out full biocompatibility, functionality, and
      tissue incorporation data that are suitable for regulatory consideration for
      first-in-man experiences. Central to this algorithm is the choice of animal
      models and the real-time monitoring of the implanted construct performance.

PMID- 28762882
TI  - Acute Pesticide-Related Illness Among Farmworkers: Barriers to Reporting to
      Public Health Authorities.
AB  - Farmworkers are at high risk of acute occupational pesticide-related illness
      (AOPI) and AOPI surveillance is vital to preventing these illnesses. Data on such
      illnesses are collected and analyzed to identify high-risk groups, high-risk
      pesticides, and root causes. Interventions to address these risks and root causes
      include farmworker outreach, education, and regulation. Unfortunately, it is well
      known that AOPI is underreported, meaning that the true burden of this condition
      remains unknown. This article reviews the barriers to reporting of farmworker
      AOPI to public health authorities and provides some practical solutions.
      Information is presented using the social-ecological model spheres of influence.
      Factors that contribute to farmworker AOPI underreporting include fear of job
      loss or deportation, limited English proficiency (LEP), limited access to health
      care, lack of clinician recognition of AOPI, farmworker ineligibility for
      workers' compensation (WC) benefits in many states, insufficient resources to
      conduct AOPI surveillance, and constraints in coordinating AOPI investigations
      across state agencies. Solutions to address these barriers include: emphasizing
      that employers encourage farmworkers to report safety concerns; raising
      farmworker awareness of federally qualified health centers (FQHCs) and increasing
      the availability of these clinics; improving environmental toxicology training to
      health-care students and professionals; encouraging government agencies to
      investigate pesticide complaints and provide easy-to-read reports of
      investigation findings; fostering public health reporting from electronic medical
      records, poison control centers (PCCs), and WC; expanding and strengthening AOPI
      state-based surveillance programs; and developing interagency agreements to
      outline the roles and responsibilities of each state agency involved with
      pesticide safety.

PMID- 28762884
TI  - The effect of advocacy for overcoming stigma on posttraumatic growth: Focusing on
      childhood cancer survivors.
AB  - The aim of this study was to investigate both strategies for coping with stigma
      and the effects of participating in advocacy. The participants were childhood
      cancer survivors who had been diagnosed before the age of 18 years who had
      completed treatment. An embedded-design mixed-methods approach was used with 30
      interview scripts, and 145 survey results were collected. Coping strategies for
      the stigma of cancer were "secrecy, avoid stereotypes, and discrimination" and
      "disclosure of medical history." Participation in advocacy confirmed self-worth,
      helped in achievement, and promoted social skills. Quantitative analysis showed
      that greater advocacy participation was associated with higher levels of
      posttraumatic growth. This study could provide support for advocacy among
      childhood cancer survivors by demonstrating its positive effects.

PMID- 28762885
TI  - Spring and early summer species of Cortinarius, subgenus Telamonia, section
      Colymbadini and /Flavobasilis, in the mountains of western North America.
AB  - Seven species of Cortinarius, subgenus Telamonia, section Colymbadini and
      /Flavobasilis, are reported from conifer forests in the mountains of western
      North America. They typically produce basidiomes in the spring and summer. Only
      one species, C. colymbadinus, is widespread, occurring in Europe and western
      North America, but to date not reported from California. Cortinarius bridgei, C.
      flavobasilis, C. rumoribrunsi, C. vernalishastensis, and C. vernalisierraensis
      are new species. The first two are found throughout the western mountains,
      whereas the latter three thus far are known only from California. Cortinarius
      ahsii, a common species in the Rocky Mountains and Pacific Northwest, also has
      not been recorded from California.

PMID- 28762886
TI  - Using the Socio-Ecological Model to Frame Agricultural Safety and Health
      Interventions.
AB  - The Socio-Ecological Model (SEM) is a conceptual framework depicting spheres of
      influence over human behavior that has been applied in public health settings for
      nearly five decades. Core principles of all variations of the SEM are the
      multiple influences over an individual's behaviors, the interactions of those
      influences, and the multilevel approaches that can be applied to interventions
      intended to modify behaviors. A project team modified the standard SEM to address
      interventions for protecting children from agricultural disease and injury. The
      modified SEM placed the "child in the farm environment" at the core with five
      interrelated levels (spheres) of influence over the child. This framework
      provides guidance on how a multifaceted, multilevel intervention can maximize the
      potential for impact on behaviors and decisions made by parents/adults
      responsible for the safety of children on farms. An example of how this model
      could work to safeguard youth operating tractors is provided.

PMID- 28762887
TI  - Racial and Ethnic Differences in Tobacco Information Seeking and Information
      Sources: Findings From the 2015 Health Information National Trends Survey.
AB  - This article describes sources of health information, types of tobacco
      information sought, and trust in sources of tobacco information among U.S.
      racial/ethnic groups (Whites, Blacks, Hispanics, Asian and Pacific Islanders, and
      Other). Cross-sectional data (N = 3,788) from a nationally representative survey,
      HINTS-FDA 2015, were analyzed to examine unadjusted and adjusted associations
      between race/ethnicity and (a) first source of health information, (b) tobacco
      information seeking, and (c) trust in sources of tobacco information. Adjusted
      associations controlled for current tobacco product use and sociodemographic
      variables. Findings indicated that the Internet was the most common first source
      of health information while health care providers were the second most common
      source for all racial/ethnic groups. Tobacco-related health information seeking
      was more prevalent than other tobacco product information seeking. Unadjusted
      analyses indicated that a higher proportion of Whites sought other tobacco
      product information compared to Asians and Pacific Islanders. Trust was rated
      highest for doctors while trust for health organizations was rated second
      highest. Asians and Pacific Islanders had higher trust in the government compared
      to all other groups. Blacks had higher trust in religious organizations compared
      to all other groups besides Hispanics. Blacks had higher trust for tobacco
      companies compared to Whites and Other. Many of these differences were attenuated
      in adjusted analyses. This research has implications for tobacco control practice
      and policymaking by identifying potential dissemination strategies.

PMID- 28762888
TI  - Ten years of implementing screening, brief intervention, and referral to
      treatment (SBIRT): Lessons learned.
AB  - The US Surgeon General recently issued a comprehensive report indicating that
      substance use is a major public health concern that must be addressed using a
      number of strategies. Screening, brief intervention, and referral to treatment
      (SBIRT) is one such strategy. SBIRT Colorado, funded by the Substance Abuse and
      Mental Health Services Administration (SAMHSA), has implemented a statewide
      initiative for the past 10 years that has provided ample opportunities to
      identify key components for successful implementation. Successful implementation
      requires (1) strong clinical and management advocates; (2) full integration of
      services into practices' workflow utilizing technology whenever possible; (3)
      interprofessional team approaches; (4) appropriate options for the small
      proportion of patients screening positive for a possible substance use disorder;
      (5) cannabis screening that accounts for legalization, and interventions that
      acknowledge differences between alcohol and cannabis use; (6) incorporating SBIRT
      into standard health care professionals' training; and (7) addressing the
      significant issues regarding reimbursement through private and public payers for
      SBIRT services. Implementing and sustaining SBI as a standard of integrated care
      is essential to reduce the burden of substance use. Interdisciplinary approaches,
      technology, and training to increase practitioner confidence and skill are
      fundamental.

PMID- 28762889
TI  - Orthodontic management of a dental concrescence: a case report.
AB  - Dental concrescence is a rare dental abnormality resulting in the joining of two
      teeth at the level of the cementum. This is the first reported case of the
      orthodontic management of a dental concrescence and the options for patient
      treatment are discussed. In this case, a compromised occlusal result was accepted
      with restorative masking of the affected teeth.

PMID- 28762890
TI  - The latency of the light response is modulated by the phosphorylation state of
      Drosophila TRP at a specific site.
AB  - Drosophila photoreceptors respond to oscillating light of high frequency (~100
      Hz), while increasing the oscillating light intensity raises the maximally
      detected frequency. Recently, we reported that dephosphorylation of the light
      activated TRP ion channel at S936 is a fast, graded, light-, and Ca2+-dependent
      process. We further found that this process affects the detection limit of high
      frequency oscillating light. Accordingly, transgenic Drosophila, which do not
      undergo phosphorylation at the S936-TRP site (trpS936A), revealed a short time
      interval before following the high stimulus frequency (oscillation-lock response)
      in both dark- and light-adapted flies. In contrast, the trpS936D transgenic
      flies, which mimic constant phosphorylation, showed a long-time interval to
      oscillation-lock response in both dark- and light-adapted flies. Here we extend
      these findings by showing that dark-adapted trpS936A flies reveal light-induced
      current (LIC) with short latency relative to trpWT or trpS936D flies, indicating
      that the channels are a limiting factor of response kinetics. The results
      indicate that properties of the light-activated channels together with the
      dynamic light-dependent process of TRP phosphorylation at the S936 site determine
      response kinetics.

PMID- 28762891
TI  - Coping strategies used by parents of children with traumatic brain injury: A
      cross-sectional study of Palestinians and Israelis.
AB  - This study examined the use and helpfulness of coping strategies and patterns
      among parents of children with traumatic brain injury (TBI). Participants were
      122 Arab-Israeli, Jewish-Israeli, and Palestinian parents of 65 children with TBI
      following their discharge from pediatric rehabilitation hospital. Family-focused
      strategies were highly prevalent and most helpful among both mothers and fathers.
      Jewish mothers reported that support coping pattern (but not medical or family)
      was more helpful than did Arab-Israeli and Palestinian mothers. The findings
      highlight the need to promote effective coping among mothers of children with TBI
      with low levels of income and education and underscore the need for continuous
      long-term professional support to parents of children with TBI after hospital
      discharge.

PMID- 28762892
TI  - Physiological response to firefighting activities of various work cycles using
      extended duration and prototype SCBA.
AB  - Firefighters' self-contained breathing apparatus (SCBA) protects the respiratory
      system during firefighting but increases the physiological burden. Extended
      duration SCBA (>30 min) have increased air supply, potentially increasing the
      duration of firefighting work cycles. To examine the effects of SCBA
      configuration and work cycle (length and rest), 30 firefighters completed seven
      trials using different SCBA and one or two bouts of simulated firefighting
      following work cycles common in the United States. Heart rate, core temperature,
      oxygen consumption, work output and self-reported perceptions were recorded
      during all activities. Varying SCBA resulted in few differences in these
      parameters. However, during a second bout, work output significantly declined
      while heart rates and core temperatures were elevated relative to a single bout.
      Thirty seven per cent of the subjects were unable to complete the second bout in
      at least one of the two-bout conditions. These firefighters had lower fitness and
      higher body mass than those who completed all assigned tasks. Practitioner
      Summary: The effects of extended duration SCBA and work/rest cycles on
      physiological parameters and work output have not been examined. Cylinder size
      had minimal effects, but extended work cycles with no rest resulted in increased
      physiological strain and decreased work output. This effect was more pronounced
      in firefighters with lower fitness.

PMID- 28762893
TI  - Overlapping MicroRNA Expression in Saliva and Cerebrospinal Fluid Accurately
      Identifies Pediatric Traumatic Brain Injury.
AB  - To assess the accuracy and physiological relevance of circulating microRNA
      (miRNA) as a biomarker of pediatric concussion, we compared changes in salivary
      miRNA and cerebrospinal fluid (CSF) miRNA concentrations after childhood
      traumatic brain injury (TBI). A case-cohort design was used to compare
      longitudinal miRNA concentrations in CSF of seven children with severe TBI
      against three controls without TBI. The miRNAs "altered" in CSF were interrogated
      in saliva of 60 children with mild TBI and compared with 18 age- and sex-matched
      controls. The miRNAs with parallel changes (Wilcoxon rank sum test) in CSF and
      saliva were interrogated for predictive accuracy of TBI status using a
      multivariate regression technique. Spearman rank correlation identified
      relationships between miRNAs of interest and clinical features. Functional
      analysis with DIANA mirPath identified related mRNA pathways. There were 214
      miRNAs detected in CSF, and 135 (63%) were also present in saliva. Six miRNAs had
      parallel changes in both CSF and saliva (miR-182-5p, miR-221-3p, mir-26b-5p, miR
      320c, miR-29c-3p, miR-30e-5p). These miRNAs demonstrated an area under the curve
      of 0.852 for identifying mild TBI status. Three of the miRNAs exhibited
      longitudinal trends in CSF and/or saliva after TBI, and all three targeted mRNAs
      related to neuronal development. Concentrations of miR-320c were directly
      correlated with child and parent reports of attention difficulty. Salivary miRNA
      represents an easily measured, physiologically relevant, and accurate potential
      biomarker for TBI. Further studies assessing the influence of orthopedic injury
      and exercise on peripheral miRNA patterns are needed.

PMID- 28762894
TI  - How patients navigate the diagnostic ecosystem in a fragmented health system: a
      qualitative study from India.
AB  - BACKGROUND: Depending on a country's diagnostic infrastructure, patients and
      providers play different roles in ensuring that correct and timely diagnosis is
      made. However, little is known about the work done by patients in accessing
      diagnostic services and completing the 'test and treat' loop. OBJECTIVE: To
      address this knowledge gap, we traced the diagnostic journeys of patients with
      tuberculosis, diabetes, hypertension and typhoid, and examined the work they had
      to do to arrive at a diagnosis. METHODS: This paper draws on a qualitative study,
      which included 78 semi-structured interviews and 13 focus group discussions with
      patients, public and private healthcare providers, community health workers, test
      manufacturers, laboratory technicians, program managers and policymakers. Data
      were collected between January and June 2013 in rural and urban Karnataka, South
      India, as part of a larger project on barriers to point-of-care testing. We
      reconstructed patient diagnostic processes retrospectively and analyzed emerging
      themes and patterns. RESULTS: The journey to access diagnostic services requires
      a high level of involvement and immense work from patients and/or their
      caretakers. This process entails overcoming cost and distance, negotiating social
      relations, continuously making sense of their illness and diagnosis, producing
      and transporting samples, dealing with the social consequences of diagnosis, and
      returning results to the treating provider. The quality and content of
      interactions with providers were crucial for completion of test and treat loops.
      If the tasks became overwhelming, patients opted out, delayed being tested,
      switched providers and/or reverted to self-testing or self-treatment practices.
      CONCLUSION: Our study demonstrated how difficult it can be for patients to
      complete diagnostic journeys and how the health system works as far as
      diagnostics are concerned. If new point-of-care tests are to be implemented
      successfully, policymakers, program officers and test developers need to find
      ways to ease patient navigation through diagnostic services.

PMID- 28762895
TI  - Encapsulation of Equine Endothelial Colony Forming Cells in Highly Uniform,
      Injectable Hydrogel Microspheres for Local Cell Delivery.
AB  - A common challenge in cell therapy is the inability to routinely maintain
      survival and localization of injected therapeutic cells. Delivering cells by
      direct injection increases the flexibility of clinical applications, but may
      cause low cell viability and retention rates due to the high shear forces in the
      needle and mechanical wash out. In this study, we encapsulated endothelial colony
      forming cells (ECFCs) in poly(ethylene glycol)-fibrinogen (PF) hydrogel
      microspheres using a custom-built microfluidic device; this system supports rapid
      encapsulation of high cell concentrations (10 million cells per mL) and resulting
      cell-laden microspheres are highly uniform in shape and size. The encapsulated
      ECFCs were shown to have >95% viability and continued to rapidly proliferate.
      Expression of cell markers (von Willebrand factor, CD105, and CD14), the ability
      to form tubules on basement membrane matrix, and the ability to take up low
      density lipoprotein were similar between pre- and post-encapsulated cells.
      Viability of encapsulated ECFCs was maintained after shear through 18-23-gauge
      needles. Ex vivo and in vivo cell delivery studies were performed by
      encapsulating and injecting autologous equine ECFCs subcutaneously into distal
      limb full-thickness wounds of adult horses. Injected ECFCs were visualized by
      labeling with fluorescent nanodots before encapsulation. One week after
      injection, confocal microscopy analysis of biopsies of the leading edges of the
      wounds showed that the encapsulated ECFCs migrated into the surrounding host
      tissue indicating successful retention and survival of the delivered ECFCs.
      Rapid, scalable cell encapsulation into PF microspheres was demonstrated to be
      practical for use in large animal cell therapy and is a clinically relevant
      method to maintain cell retention and survival after local injection.

PMID- 28762896
TI  - Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute
      stroke: Rationale, design and protocol for the Rapid Intervention with Glyceryl
      trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053).
AB  - Rationale Vascular nitric oxide levels are low in acute stroke and donors such as
      glyceryl trinitrate have shown promise when administered very early after stroke.
      Potential mechanisms of action include augmentation of cerebral reperfusion,
      thrombolysis and thrombectomy, lowering blood pressure, and cytoprotection. Aim
      To test the safety and efficacy of four days of transdermal glyceryl trinitrate
      (5 mg/day) versus sham in patients with ultra-acute presumed stroke who are
      recruited by paramedics prior to hospital presentation. Sample size estimates The
      sample size of 850 patients will allow a shift in the modified Rankin Scale with
      odds ratio 0.70 (glyceryl trinitrate versus sham, ordinal logistic regression) to
      be detected with 90% power at 5% significance (two-sided). Design The Rapid
      Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) is
      a multicentre UK prospective randomized sham-controlled outcome-blinded parallel
      group trial in 850 patients with ultra-acute (<=4 h of onset) FAST-positive
      presumed stroke and systolic blood pressure >=120 mmHg who present to the
      ambulance service following a 999 emergency call. Data collection is performed
      via a secure internet site with real-time data validation. Study outcomes The
      primary outcome is the modified Rankin Scale measured centrally by telephone at
      90 days and masked to treatment. Secondary outcomes include: blood pressure,
      impairment, recurrence, dysphagia, neuroimaging markers of the acute lesion
      including vessel patency, discharge disposition, length of stay, death,
      cognition, quality of life, and mood. Neuroimaging and serious adverse events are
      adjudicated blinded to treatment. Discussion RIGHT-2 has recruited more than 500
      participants from seven UK ambulance services. Status Trial is ongoing. Funding
      British Heart Foundation. Registration ISRCTN26986053.

PMID- 28762897
TI  - Sudden unexpected death caused by stroke: A nationwide study among children and
      young adults in Denmark.
AB  - Background Stroke is the fifth leading cause of death in young individuals
      globally. Data on the burden of sudden death by stroke are sparse in the young.
      Aims The aim of this study was to report mortality rates, cause of death, stroke
      subtype, and symptoms in children and young adults who suffered sudden death by
      stroke. Methods We conducted a retrospective, nationwide study including all
      deaths within Danish borders between 2000-2009 and 2007-2009 in persons aged 1-35
      years and 36-49 years, respectively. Two physicians identified all sudden death
      cases through review of all death certificates. All available autopsy reports and
      records from hospitals and general practitioners were retrieved and a neurologist
      identified all sudden death by stroke cases. Results Of the 14,567 deaths in the
      10-year period, there were 1,698 sudden death cases, of which 52 (3%) were sudden
      death by stroke. There was a male predominance (56%) and the median age was 33
      years. The incidence of sudden death by stroke in individuals aged 1-49 years was
      0.19 deaths per 100,000 person-years. Stroke was hemorrhagic in 94% of cases,
      whereof subarachnoid hemorrhage was the cause of death in 63% of cases. Seventeen
      (33%) cases contacted the healthcare system because of neurological symptoms,
      whereof one was suspected of having a stroke (6%). Conclusions Sudden death by
      stroke in children and young adults occurs primarily due to hemorrhagic stroke.
      We report a high frequency of neurological symptoms prior to sudden death by
      stroke. Increased awareness among healthcare professionals towards stroke
      symptoms in children and young adults may lead to earlier detection of stroke,
      and thereby potentially lowering the incidence of sudden death by stroke.

PMID- 28762898
TI  - A score for paroxysmal atrial fibrillation in acute ischemic stroke.
AB  - Aim Many patients with ischemic stroke have paroxysmal atrial fibrillation that
      may be difficult to detect. We sought to identify markers of paroxysmal atrial
      fibrillation and construct a score that may help the clinician to select patients
      for anticoagulation even if investigations do not disclose atrial fibrillation.
      Methods A group of patients with acute ischemic stroke and TIA and documented
      paroxysmal atrial fibrillation was compared to a group of patients with ischemic
      stroke and TIA and no known paroxysmal atrial fibrillation and sinus rhythm on
      Holter monitoring. Clinical features, blood tests, ECG, and MRI findings were
      compared. Sensitivity and specificity of significant markers for paroxysmal
      atrial fibrillation were calculated. A simple score based on independent markers
      for paroxysmal atrial fibrillation was constructed. Results Out of 3480 patients
      with TIA or ischemic stroke, 237 (19%) had paroxysmal atrial fibrillation and
      1002 (81%) had sinus rhythm. On univariate analyses, significant markers for
      paroxysmal atrial fibrillation included increasing age, females, prior ischemic
      stroke, myocardial infarction, other heart diseases, pathologic troponin, embolic
      stroke and stroke in different arterial territories (all P < .01). A score
      including age dichotomized at 75 years, cardiac disease and troponin was
      constructed. Conclusion We identified many markers for paroxysmal atrial
      fibrillation and constructed a score that may help the clinician to select
      patients for anticoagulation even if investigations do not disclose paroxysmal
      atrial fibrillation.

PMID- 28762899
TI  - [Predictors of Cardiorespiratory Complications in Patients With Ischemic Heart
      Disease After Coronary Artery Bypass Grafting].
AB  - PURPOSE: to elucidate predictors of cardiorespiratory complications during the
      early postoperative period after coronary artery bypass grafting (CABG) in
      patients with ischemic heart disease (IHD). MATERIAL AND METHODS: We examined 180
      patients with IHD (mean age 59.3+/-1.23years). Prior to surgery we assessed their
      clinical and functional status including state of respiratory function.
      Predictors of complications were determined by univariate logistic regression
      analysis. RESULT AND CONCLUSIONS: Early postoperative complications in this group
      of patients were atrial fibrillation, prolonged mechanical ventilation, and
      cognitive disorders. Main predictors of these complications were preoperative
      abnormalities of respiratory function (presence of chronic obstructive pulmonary
      disease, decreased efficiency of pulmonary ventilation), and concomitant diseases
      such as type 2 diabetes and multifocal atherosclerosis.

PMID- 28762900
TI  - [The Problem of Minimally Changed Coronary Arteries at Elective Coronary
      Angiography].
AB  - AIM: to study rates and possible causes of detecting "clean" coronary arteries at
      elective coronary angiography. MATERIAL AND METHODS: Medical records of 711
      patients who had undergone elective coronary angiography (ECAG) between 01/04 and
      31/05 2014 were retrospectively reviewed. Four groups were distinguished: group 1
      - patients with normal coronary arteries (n=234), group 2 - patients with
      coronary artery stenoses (CAS) <60% (n=94), group 3 - patients with 60-69% CAS
      (n=22), group 4 - patients with CAS more or equal 70% (n=361). RESULTS: Most
      patients were men (p<0.001), except group 1, where women prevailed (p<0.05).
      Patients in groups 3 and 4 were older than in groups 1 and 2 (p=0.019). Symptoms
      of angina were less likely to be found in group 1 (p<0.001). History of
      myocardial infarction (MI) prevailed in group 4 (p<0.001). Arrhythmias were
      detected more frequently in group 1 (p<0.001); there were less diabetics in this
      group (p=0.010). Group 1 contained more patients examined before cardiac valve
      surgery (p<0.001). Typical angina was more often found in group 4, whereas
      atypical angina - in group 1 (p<0.001). Cardialgia prevailed in groups 1 and 2
      (p<0.001). Holter ECG monitoring was used more frequently in group 1 (p<0.001).
      Symptoms of latent coronary insufficiency were mainly reported in group 1
      (p=0.006). The pretest probability of ischemic heart disease (IHD) was higher in
      groups 2 and 4 compared to group 1 (p<0.001). CONCLUSION: Among patients who had
      undergone ECAG 32.9% had no CAS. Younger females without history of MI and
      diabetes as well as patients with atypical angina or cardialgia prevailed in this
      group. This group of patients had the lowest pretest probability of IHD (58%).
      Patients without CAS were more often scheduled for EGAG before valvular heart
      surgery and because of cardiac arrhythmias.

PMID- 28762901
TI  - [The First Experience of Using Very Long Stents Covered With Sirolimus (4060 mm)
      in the Treatment of Patients With Extensive and Diffuse Lesions of the Coronary
      Arteries].
AB  - OBJECTIVES: To assess the clinical outcome of one year follow-up in patients with
      diffuse long lesions treated with extra-long sirolimus-eluting stents. METHODS
      AND RESULTS: 85 patients underwent implantation of very long BioMime stents
      during the period from March 2014 to February 2016. RESULTS: The angiographic
      success rate was 100%, clinical success was observed in 98.8% cases (one patient
      developed periprocedural MI). The additional back-up support for stent delivery
      was used in 11 (12.9%) patients (the "buddy wire" technique in 6 pts and
      Guidzilla catheter in 2 pts.). Cumulative MACE rate at 12 months was 9.4% with
      1.1% myocardial infarction and 5.9% TLR. One patient died 6 month after stent
      implantation from massive pulmonary thromboembolism. None of the patients had
      subacute or late stent thrombosis. Follow-up angiography was performed in 48
      (68.5%) patients, 5 (10.4%) patients demonstrated restenoses. CONCLUSION: The use
      of extra-long sirolimus-eluting stents is associated with good procedural and one
      year clinical outcomes in complex patients with long and diffuse lesions.

PMID- 28762902
TI  - [Outcomes of Various Revascularisation Strategies in the Elderly STEMI Patients
      With Multi-Vessel Coronary Pathology].
AB  - AIM: to assess safety and efficacy of single stage complete revascularization by
      multivessel stenting as primary percutaneous coronary intervention (pPCI) in
      elderly and middle aged patients with acute ST-elevation myocardial infarction
      (STEMI). MATERIAL AND METHODS: We included in this analysis data on 327 of 1690
      STEMI patients who had undergone pPCI from 2009 to 2013. Age of 103 patients was
      more or equal 65 and of 224 less or equal 64 years. Multivessel stenting (MS)
      during pPCI was carried out in 26 and 65, while strategy of staged
      revascularization (SR) was implemented in 77 and 129 individuals among older and
      younger patients, respectively. During follow-up for 12 months we registered
      deaths, myocardial infarctions, and unplanned target vessel revascularizations.
      RESULTS: In each age group ( more or equal 65 and less or equal 64 years) there
      were no significant differences in clinical and demographic characteristics
      between subgroups of patients subjected to MS and SR. MS appeared to be safe and
      effective irrespective of age. Mortality during first 30-days was higher among
      patients aged more or equal 65 years. However, within each age group there were
      no significant differences in 1 year results between MS and SR subgroups.

PMID- 28762904
TI  - [Comparative Efficacy and Safety of Two Medicine Forms of Lappaconitin
      Hydrobromide in Patients With Ventricular Extrasystole Without Organic Pathology
      of the Heart].

PMID- 28762903
TI  - [Adherence of Patients to Antihypertensive Therapy With Combination of
      Perindopril and Indapamide According to Data of the FORSAGE Program].
AB  - AIM: to assess adherence of patients to antihypertensive therapy with fixed
      perindopril and indapamide combination (FPIC) as well as to elucidate causes of
      changes of therapy after 6 months. MATERIAL AND METHODS: In 6 months after
      termination of the FORSAGE observational program we interviewed over telephone
      148 of 1299 patients who achieved target blood pressure (BP) values. RESULTS:
      Adherence to treatment was high - 67.5% of patients continued to take the drug.
      In 87.9% of patients BP was kept on target level (<140 and 90 mm Hg), in 12.1% BP
      was above this level. Most patients were satisfied by results of treatment.
      Infrequent hypertensive crises persisted in 6.1% of patients; 3% of patients
      sought emergency service. Among 48 patients who stopped taking FPIC 22 (45.8%)
      made this decision themselves, 11 - on physicians advice. Main causes of
      cancellation of treatment were high cost of the drug, its absence in the list of
      concessional mediciations, physicians statement "course treatment completed,
      condition improved". Among those who stopped treatment 10 patients could not
      report values of their BP; in 28 (58.3%) BP was at and in 10 (20.8%) above target
      level; crises were registered in 8.3% of patients, 4.2% of patients called
      ambulances, 1 patient suffered stroke. Of 48 patients who stopped treatment with
      FLIC 19 consented to self report assessment health status; 84% of reported scores
      were above 5, but no score was equal to 9 or 10.

PMID- 28762905
TI  - [Atrial Fibrillation After Coronary Artery Bypass Grafting].
AB  - PURPOSE: to identify the role of factors of inflammation and myocardial ischemia
      in the development of atrial fibrillation (AF) in the early postoperative period
      after coronary artery bypass grafting (CABG). METHODS: We enrolled in this study
      96 patients with ischemic heart disease who had undergone CABG. Patients were
      divided into 2 groups: (1) without postoperative AF (n=67, 80.6% men, mean age
      57.9+/-7.3 years), (2) with early new-onset AF after CABG (n=29, 86% men, mean
      age 64.0+/-8.4 years). RESULTS: AF occurred on average 4.9+/-3.8 days after
      surgery. Concentrations of interleukin-10, C-reactive protein, fibrinogen,
      troponin were not significantly different between two groups both before and
      after CABG. At multivariate analysis the following parameters were related to
      development of AF in postoperative period: left atrial dimension >41 mm (odds
      ratio [OR] 3.6 (95% confidence interval [CI] 1.2-5.8, p=0.0002), interleukin-6
      level >68 pg/ml (OR 3.2, 95%CI 1.8-4.7, p=0.009), interleukin-8 level >9.5 pg/ml
      (OR 2.9, 95% CI 1.4-6.7, p=0.009). CONCLUSION: Our research shows significant
      increase of interleukin-6 and interleukin-8 in patients with AF after CABG what
      confirms the role of inflammation factors in development of this complication.

PMID- 28762906
TI  - [Efficacy of Short-Term Therapy With Meldonium in Patients With Chronic Heart
      Failure of Ischemic Etiology and Type 2 Diabetes Mellitus].
AB  - PURPOSE: to assess efficacy and endotheliotropic properties of short-term
      addition of meldonium to basic therapy of patients with chronic ischemic heart
      failure and type 2 diabetes. RESULTS AND CONCLUSION: The study demonstrated the
      ability of meldonium to significantly improve endothelial function and the state
      of microcirculatory vascular bed, as well as to influence beneficially heart rate
      variability.

PMID- 28762907
TI  - [Subpopulation Composition of CD4+ T-lymphocytes as Factor Contributing to the
      Progression of Atherosclerosis of Carotid Arteries].
AB  - AIM: to assess prognostic significance of blood content of regulatory and
      effector T-lymphocytes for progression of atherosclerosis (AS) of carotid
      arteries. MATERIAL AND METHODS: We enrolled in this study 33 men with various
      severity of carotid AS. Carotid artery duplex scan was done at admission and in 1
      year after enrollment. AS progression was defined as appearance of novel stenosis
      in common or internal carotid artery or more or equal 5% increase of preexisting
      stenosis. Peripheral blood lymphocyte phenotyping was performed by direct
      immunofluorescence and flow cytometry at the enrollment. T-helpers (Th) 1 were
      identified as CD4+IFNgamma+ cells, Th2 - CD4+IL4+, activated T-cells (T-act) -
      D4+CD25lowCD127high, regulatory T-cells (T-reg) - D4+CD25highCD127 low and
      CD4+FoxP3+, Th17 - CD4+IL17a+ cells. RESULTS: Progression of carotid AS was
      observed in 18 patients. Basal values of Th17 were higher while ratio T-reg/Th17
      was lower in patients with compared with those without AS progression. ROC
      analysis showed high sensitivity and specificity of blood levels of Th17, T-act
      and T-reg/Th17 ratio for carotid AS progression during one year in patients with
      low density lipoprotein cholesterol (LDLCH) level below 3.5 mmol/l. CONCLUSION:
      The imbalance between circulating levels of regulatory T-cells and T-helpers 17
      with the prevalence of proinflammatory T-helpers 17 may reflect a predisposition
      for carotid AS progression, what also refers to patients with relatively low
      LDLCH.

PMID- 28762908
TI  - [Blood Levels of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Men
      from Different Population Groups and Its Relation to Unfavorable Long-Term
      Prognosis].
AB  - AIM: of the study was to investigate blood levels of proprotein convertase
      subtilisin/kexin type 9 (PCSK9) in men from different population subgroups, their
      associations with cardiovascular risk factors and with unfavorable 7-years long
      term prognosis. MATERIAL AND METHODS: The study included three subgroups of men
      from a population sample of residents of Novosibirsk, 44-73 years old, not
      receiving lipid-lowering drugs: subgroup of population proper (183 men), subgroup
      with hypercholesterolemia (46 men), and subgroup with hypocholesterolemia (18
      men). Blood level of PCSK9 was determined by ELISA using the test-systems "Human
      Proprotein Convertase 9/PCSK9 Immunoassay". Study endpoints (myocardial
      infarction, cardiovascular death) were registered during 7 years after baseline
      examination of subgroups using the data of the Registers of myocardial infarction
      and cardiovascular mortality. RESULTS: Distribution of PCSK9 protein in subgroups
      with hyper- and hypocholesterolemia was normal. In the subgroup of population
      proper it was abnormal with leftward shift. PCSK9 protein concentration in the
      subgroup with hypercholesterolemia was 1.2 times higher than in the population
      subgroup. PCSK9 protein level correlated significantly with blood levels of total
      cholesterol (CH), low density lipoprotein (LDL) CH, and glucose. Only 15% of
      PCSK9 variability was due to the influence of other factors (R Square=0.155,
      p<0.001). Factors with significant influence on blood level of PCSK9 protein were
      levels of high density lipoprotein CH (=0.238, p=0.023), triglycerides (=0.253,
      p=0.049) and LDL CH (=0.751, p=0.009). Multivariate regression analysis revealed
      significant independent association of PCSK9 protein levels with cardiovascular
      death during period of registration (7-years) (p=0.048, OR=1.01). This result
      indicates that in men increase of blood level of PCSK9 protein by 1ng/ml
      independently of other parameters increases relative risk of cardiovascular death
      during following 7 years by 1%.

PMID- 28762909
TI  - [Changes of Concentration of Irisin in Blood of Patients With Hypertensive
      Disease After Physical Effort].

PMID- 28762910
TI  - [Fixed-Drug Combination Amlodipine, Indapamide and Perindopril: New Horizons of
      Antihypertensive Therapy].
AB  - High prevalence of arterial hypertension and low rate of blood pressure (BP)
      control in patients with arterial hypertension require more intensive approaches
      to antihypertensive therapy. Every patient with arterial hypertension is
      characterized by different predominant pathophysiologic mechanisms in different
      periods of his life. Because of impact on different pathophysiologic mechanisms
      combined antihypertensive therapy allows to achieve more pronounced BP reduction,
      decrease heterogeneity of response and alleviate side effects of each component.
      Use of fixed drug combinations improves adherence to treatment and thus its
      efficacy. Novel fixed-dose combination of amlodipine, indapamide and perindopril
      fully realizes principles underlying modern antihypertensive therapy.
      Antihypertensive effectiveness of components of this combination has been
      confirmed by the results of international trials.

PMID- 28762911
TI  - [Clinico-Pathogenetic Relationship of Cardiovascular Diseases and Chronic
      Obstructive Pulmonary Disease].
AB  - Close relationship between cardiovascular diseases and chronic obstructive
      pulmonary disease (COPD) has attracted attention over the past 15 years as one of
      the aspects of systemic manifestations of COPD. The high prevalence of
      cardiovascular diseases in patients with COPD is explained within the concept of
      low-level persistent systemic inflammation. This review presents current data on
      the prevalence of cardiovascular diseases and mortality in the population of
      patients with COPD.

PMID- 28762912
TI  - [The Experience of Use Triple Antithrombotic Therapy in Patients With Acute
      Coronary Syndrome and Atrial Fibrillation].
AB  - AIM: In real life to evaluate the effectiveness and safety of apixaban with
      double antiplatelet therapy for prevention of stroke and systemic embolism in
      patients with non-valvular atrial fibrillation and the recent episode of acute
      coronary syndrome without ST segment elevation. MATERIALS AND METHODS: 8 patients
      with atrial fibrillation and the recent (8-14 days after the onset of symptoms of
      ACS) episode of acute coronary syndrome without ST segment elevation were
      involved into the research. The effectiveness (deaths, stroke and systemic
      embolism) and the safety (major clinically significant and not significant
      bleeding) were investigated within 3 months. RESULTS: There were no any strokes,
      systemic embolism, deaths during observational period. Nasal and mild gingival
      hemorrhages (not requiring medical intervention) were noted in 2 patients during
      the first month of treatment and two patients experienced non-permanent
      petechiae. Major and clinically significant bleeding was not registered.
      onclusions: the use of oral anticoagulant apixaban 5 mg BID or 2.5 mg BID with
      double antiplatelet therapy in patients with non-valvular atrial fibrillation and
      the recent episode of acute coronary syndrome without ST segment elevation is
      effective and safe for the prevention of stroke and systemic embolism during 3
      months of treatment. Future researches are required.

PMID- 28762913
TI  - [Prevention of Cardiovascular Events: Are All Recommendations Applicable to
      Elderly Patients With Senile Asthenia?]
AB  - Primary prevention of cardiovascular events is based on achievement of optimal
      control of risk factors - arterial hypertension, dyslipidemia, glycemia - in
      accordance with current recommendations of scientific societies. But most rapidly
      growing segment of population - elderly and old individuals - have been
      underrepresented in randomized clinical trials underlying recommendations on
      primary and secondary prevention. That is why it is problematic to directly apply
      recommendations to patients from this group of population. In addition, old
      patients are characterized by accumulation of functional deficits, development of
      syndrome of senile asthenia ("frailty"), and multimorbidity. Effect of these
      characteristics on prognosis often exceeds that of risk factors. Other important
      factor is high susceptibility of old patients to risk of development of
      unfavorable effects because of both changes of pharmacokinetics and
      pharmacodynamics of drugs and the need for multiple medicines (polypragmasy).
      While applying existing recommendations to old people one should recognize
      limitations of current knowledge on best ways of realization of approaches to
      prevention of cardiovascular prevention which effectiveness has been proved in
      younger individuals. Improvement of awareness and development of special skills
      of physicians involved in management of old patients is required for timely
      detection of the syndrome of senile asthenia. Special geriatric approaches should
      be implemented in cooperation with specialists in geriatric medicine.

PMID- 28762914
TI  - [Adaptation to Intermittent Hypoxia-Hyperoxia in the Rehabilitation of Patients
      With Ischemic Heart Disease: Exercise Tolerance and Quality of Life].
AB  - AIM: to assess effect of interval hypoxic-hyperoxic training (IT) on exercise
      tolerance and quality of life of patients with ischemic heart disease (IHD)
      receiving optimal medical therapy, as well as the safety of IHHT use. METHODS:
      Patients with stable IHD with functional class II and III angina (n=46) were
      randomized into two groups: IHHT (n=27, 15 treatments in 3 weeks), and IHHT
      imitation (n=19). Cardiopulmonary stress test was performed to evaluate the
      following parameters of exercise tolerance: peak oxygen consumption (VO2peak,
      VO2peak/kg), % of predicted peak oxygen consumption (%VO2 peak) and anaerobic
      threshold (VO2AT). MOS SF-36, SAQ, HADS questionnaires were used for assessment
      of quality of life (QL). RESULTS: Exercise tolerance (VO2peak/kg) after course of
      IHHT significantly increased (p=0.03) and remained significantly elevated during
      subsequent month (p=0.036). Marked improvement was also observed in patients
      subjective perception of QL. This was evidenced by dynamics of characteristics of
      physical functioning as well as of psychological state, significant increase of
      values on all scales of disease-specific questionnaire SAQ, reduction of
      depression and anxiety according to dynamics of HADS scores. These effects
      persisted in 1 month after IHHT. IHHT was safe and well tolerated. Side effects
      were minimal (transient slight dizziness, feeling of shortage of air) and did not
      require IHHT termination. CONCLUSION: We received clinical confirmation of safety
      and effectiveness in of IHHT in medically treated patients with stable angina.
      IHHT was associated with significant improvement of exercise tolerance,
      subjective perception of QL, reduction of number of angina attacks. Thus, IHHT
      has significant potential as component of complex treatment and rehabilitation of
      patients with stable angina.

PMID- 28762915
TI  - [Association of Serum Levels and Gene Polymorphism of Vascular Endothelium Growth
      Factor With Ischemic Heart Disease in Type 2 Diabetic Patients].
AB  - AIM: to study serum levels of vascular endothelium growth factor family peptides
      (VEGF-A, VEGF-C and VEGF-D) and functional gene polymorphisms of VEGFA gene
      (rs699947 and rs3025039) in patients with type 2 diabetes (T2D) depending on the
      presence of ischemic heart disease (IHD). MATERIALS AND METHODS: The study
      involved 196 Caucasian patients with T2D (age 43-70 years, 76 with IHD). The
      concentrations of VEGF-A, VEGF-C and VEGF-D in blood serum were determined by
      Multiplex assay. Twenty-four persons without diabetes and IHD served as controls.
      The genotyping of VEGFA polymorphism -2578A/C (rs699947) and +936C/ (rs3025039)
      was performed by TaqMan. RESULTS: Concentrations of VEGF-A and VEGF-C in patients
      with T2D were significantly lower than those in controls (p=0.03 and p=0.006,
      respectively). The level of VEGF-D showed a tendency to decrease (p=0.14).
      Patients with IHD, as compared to other patients, had higher levels of VEGF-A
      (p=0.04) and a tendency to VEGF-D increase (p=0.06). The concentration of VEGF-C
      was not different between groups. No relationships were found between VEGF-A,
      VEGF-C and VEGF-D levels, HbA1c or glucose variability parameters. C-allele and
      CC-genotype at +936 position of VEGFA were more frequent among patients with IHD
      (odds ratio 2.14 and 2.41, respectively, p=0.02). The rs699947 polymorphism was
      not related to IHD and VEGF-A levels. CONCLUSION: Patients with T2D have
      decreased serum levels of angiogenic factors VEGF-A and VEGF-C. VEGFA rs3025039
      polymorphism is associated with presence of IHD and levels of circulating VEGF-A
      in these patients.

PMID- 28762916
TI  - [Predictors of Electrical Myocardial Instability in Men With Arterial
      Hypertension and Obstructive Sleep Apnea-Hypopnea Syndrome].
AB  - OBJECTIVE: To access the detectability of corrected QT interval (QTc)
      prolongation ( more or equal 450 ms) and increased QT dispersion (QTd more or
      equal 60 ms) in men with obstructive sleep apnea-hypopnea syndrome (OSAS) and
      newly diagnosed arterial hypertension (AH). MATERIAL AND METHODS: We included in
      this study 138 men (mean age 40.5+/-6.9 years, body mass index 34.5+/-4.7 kg/m2,
      all with more or equal 3 risk factors of AH development, 34% with subclinical
      target organs damage). According to office systolic and diastolic blood pressure
      level (SBP and DBP), AH of 1st degree was diagnosed in 103 (74.6%), 2nd - in 26
      (18.9%) and 3rd - in 9 (6.5%) patients. All patients underwent 24-h
      multifunctional monitoring. According to the apnea-hypopnea index (AHI) patients
      were divided into 4 groups: I (control, n=34) with AHI less than 5/h, II (n=36)
      with AHI 5-14/h, III (n=32) with AHI 15-29/h, IV (n=36) with AHI more or equal
      30/h. RESULTS: There were no significant intergroup differences in age, body mass
      index, sleep duration, mean daytime SBP, QT and JT dispersion in the diurnal,
      daytime and nighttime periods. However, in group IV values of mean heart rate (in
      normal range), daytime DBP, nighttime SBP and DBP, QTc and JTc intervals were
      higher than in other groups. Portions of patients with prolonged QTc and
      increased QTd were 38.2 and 35.3%, 44.4 and 33.3%, 34.4 and 40.6%; 50.0 and 38.9%
      in groups I, II, III, IV, respectively. Multiple regression analysis revealed
      associations between mean diurnal QTc interval prolongation and reduction of mean
      oxygen saturation (SpO2) during sleep, and between mean diurnal JTc interval
      prolongation and increase of AHI. CONCLUSIONS: Rates of detection of QTc interval
      prolongation and QTd increase in men with newly diagnosed AH and OSAS of
      different severity were almost similar. However, there was a trend to higher
      detectability of QTc interval prolongation (50.0%) among patients with AHI more
      or equal 30/h. Reduction of mean SpO2 and AHI increase during sleep were found to
      be predictors of diurnal QTc and JTc intervals prolongation, respectively.

PMID- 28762917
TI  - [The Course of Acute Myocardial Infarction According to Date of a Retrospective
      Study].

PMID- 28762918
TI  - [Noninvasive Electrophysiological Mapping in Patients With Complete Left Bundle
      Branch Block and Different Modes of Biventricular Pacing].
AB  - OBJECTIVE: to investigate possibilities of noninvasive electrophysiological
      mapping (NEM) during biventricular (BiV) pacing and to compare the results with
      data of 12 lead ECG and tissue Doppler echocardiography (TDI). MATERIAL AND
      METHODS: The study included 25 patients with complete left bundle branch block
      (LBBB) and implanted cardiac resynchronization therapy (CRT) system. Twenty-two
      patients were CRT responders, three other patients did not demonstrate a clear
      effect. NEM was performed with "Amycard 01C EP LAB" system and multi slice
      computed tomography. RESULTS: Qualitative analysis of isochronous maps at NEM
      showed that the most homogenous color coding of the left ventricle (LV) may
      correspond to the optimal BiV pacing mode. A statistically significant positive
      correlation between the width of the QRS complex during a set BiV pacing mode and
      the standard activation deviation time, measured at NEM, for 12 segments (SD12)
      LV (r= 0,88, p<0,0001) was observed. With the minimum value of SD12 and
      biventricular QRS width at the same time, three patients had intraventricular
      dyssynchrony. A comparative analysis of NEM and TDI methods in terms of
      interventricular dyssynchrony (IVD) at LBBB revealed statistically significant
      positive correlation (r=0,58, p=0,005). CONCLUSION: These data show that both
      minimal values of QRS and SD12 at BiV pacing are not accompanied by the effect of
      CRT in all patients. The lack of response from this type of therapy is associated
      with a non-optimal position of the LV electrode. Qualitative assessment of
      isochronous maps at NEM demonstrates intraventricular dyssynchrony and can help
      in selecting the optimal mode of BiV pacing.

PMID- 28762919
TI  - [Effectiveness of Extended Myectomy in Patients With Hypertrophic Cardiomyopathy
      With Midventricular Obstruction].
AB  - PURPOSE: to assess effectiveness and safety of extended myectomy performed in
      patients with hypertrophic obstructive cardiomyopathy (HOCM) with midventricular
      obstruction. MATERIAL AND METHODS: Between 2010 and 2013 185 HOCM patients were
      operated for left ventricular outflow tract (LVOT) obstruction. Among these
      patients 32 had midventricular obstruction. Their age was 22-74 (mean 51.9+/
      14.2) years. Mean peak gradient across LVOT was 89.1+/-20.4 mm Hg, thickness of
      interventricular septum was 26.9+/-4.3 mm. Operations were guided by
      intraoperative transesophageal echocardiography (TEE). RESULTS: There were no
      early deaths. Gradient at LVOT according to TEE decreased to 15.4+/-5.7 mm Hg.
      There were no complications specific for extended myectomy (such as ventricular
      septal defect, left ventricular wall rupture, or aortic regurgitation). In 2
      (6.9%) patients permanent pacemaker was implanted because of complete atrio
      ventricular block. Mean follow-up was 18.7 (95% confidence interval [CI] 17.2 to
      20.3) months. Kaplan-Meier estimate of survival was 100% at 12 and 94.2% (95% CI
      65.8-99.1%) at 22 months. CONCLUSION: Extended myectomy can be safely and
      effectively performed in HOCM patients with midventricular obstruction and should
      be considered individually in each patient.

PMID- 28762920
TI  - [Radial Approach for Percutaneous Coronary Interventions in Patients With
      Ischemic Heart Disease: Advantages and Disadvantages, Complications Rate in
      Comparison With Femoral Approach].
AB  - During recent 10-15 years, percutaneous coronary interventions (PCI) have reached
      a new level of efficacy and safety. Rate of serious coronary complications has
      decreased. That to a greater degree exposes the problem of peripheral
      complications at the site of arterial approach. At the same time portion of
      patients older than 75 years in the total pool of PCI constantly increases.
      Number of patients with pronounced obesity also grows each year. Radial approach
      for PCI allows to substantially decrease rate of peripheral complications at the
      account of lowered rate of bleedings, and to shorten duration of hospitalization.
      In this literature review we present results of a number of relevant clinical
      studies including those which contained groups of elderly patients and of
      patients with obesity. We also have summarized main advantages and disadvantages
      of radial approach as compared with femoral approach for coronary angiography and
      PCI.

PMID- 28762921
TI  - [ECG Predictors of Prognostically Unfavorable Coronary Artery Lesions].
AB  - Medical treatment of most patients with ischemic heart disease is comparable to
      revascularization by the effect on major adverse cardiovascular events
      (myocardial infarction, cardiovascular and overall mortality), and in the long
      term, on quality of life. However, revascularization of the left main coronary
      artery lesion and lesions in the proximal segment of the anterior descending
      artery leads to a significant increase in life expectancy. ECG methods of
      detection of such prognostically unfavorable lesions of the coronary arteries can
      significantly optimize the management, hasten revascularization of the
      myocardium. In this review we have analyzed ECG methods of diagnosis of
      prognostically unfavorable lesions of the coronary arteries.

PMID- 28762922
TI  - [Prospects of Application of Remote Preconditioning at Heart Revascularization].
AB  - Remote ischemic preconditioning of the heart exerts anti-necrotic,
      antiarrhythmic, inotropic effects that have been demonstrated in clinical trials
      in cardiac surgery both in adults and children. However, so far there is no
      consensus between cardiologists regarding the impact of remote preconditioning on
      the incidence of intraoperative myocardial infarctions and mortality in the
      postoperative period. Until now there is no unanimity concerning choice of remote
      preconditioning protocol and timing of its application before cardiac surgery.

PMID- 28762923
TI  - [Candesartan is the Basis of Therapy for Arterial Hypertension in Middle-Aged
      Women].

PMID- 28762924
TI  - [The Role of non-Statin Therapy for Lowering the Concentration of low-Density
      Lipoprotein Cholesterol and Reducing the Risk of Developing Atherosclerotic
      Cardiovascular Complications].
AB  - The article provides comments on 2016 American College of Cardiology Expert
      Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL
      Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease
      Risk. The reasons for publishing this document are discussed, in particular
      appearance of results of conducted during last 3 years clinical trials of new
      highly effective non-statin medications. The article contains descriptions of
      indications, contraindications to the use of these agents as of their possible
      side effects. The preferred order of their administration in combination with
      statins in different categories of patients is also presented.

PMID- 28762925
TI  - [Angina Recurrence After Coronary Artery Bypass Grafting Caused by the Coronary
      Subclavian Steal Syndrome].
AB  - We present two cases of surgical treatment of patients with coronary artery steal
      syndrom and multifocal atherosclerosis, who previously underwent coronary artery
      bypass grafting using left internal mammary artery. In both cases carotid
      subclavian bypass was performed through supraclavicular access using synthetic
      prosthesis. This method allowed to restore blood flow in the left internal
      mammary artery, eliminate recurrent angina pectoris, and improve patients quality
      of life. The article also contains descriptions of possible methods of surgical
      correction of this pathology, their advantages and disadvantages.

PMID- 28762926
TI  - [Giant Aneurisms of Coronary Arteries in the Kawasaki Syndrome].
AB  - BACKGROUND: Kawasaki disease is an acute systemic vasculitis of childhood with
      possible coronary artery involvement which can cause acute coronary syndrome in
      children and young adults. PURPOSE: to study clinical and demographic
      characteristics of patients with Kawasaki disease with giant coronary aneurysms,
      to assess long-term prognosis in these patients. MATERIAL AND METHODS: In 2003
      2015 262 children with Kawasaki disease were examined in the University Children
      Hospital of the I.M. Sechenov Moscow State Medical University. The following
      methods of visualization of coronary arteries were used: echocardiography in all,
      multispiral computer tomography in 29, invasive coronary angiography in 11
      patients. RESULTS: Aneurysms of coronary arteries were found in 84 patients
      (32.1%), in 15 of them aneurisms were giant (internal diameter >8 mm). During
      follow-up (from 0.67 to 12, median 5.8 years) intracoronary thrombi were found in
      11 patients. Two of them had occlusions of the right coronary artery, 5 had
      coronary artery stenosis which required surgical intervention. One patient
      developed myocardial infarction before coronary surgery. CONCLUSION: Patients
      with Kawasaki disease with giant aneurysms of coronary arteries are predisposed
      to coronary thrombosis and stenosis. Long-term management of patients with
      regular examination, prevention of coronary thrombosis, and timely surgical
      intervention are necessary for lowering the risk of life-threatening
      complications.

PMID- 28762927
TI  - [Experience of Treatment of Spontaneous Rupture of Left Ventricular Posterior
      Wall After Mitral Valve Replacement].
AB  - Spontaneous rupture of the left ventricular posterior wall after mitral valve
      replacement is a severe complication and is associated with high mortality rate.
      This complication was first described in 1967 by Roberts and Morrow, which
      describe the results of autopsy of two patients. In leading clinics around the
      world left ventricular wall ruptures after mitral valve replacement account for
      up to 20% of causes of hospital mortality. Currently there is no clear-cut
      strategy of treatment of this complication. In this article we present analysis
      of both traditional and non-traditional methods of treatment of this complication
      as well as own small positive and negative experience.

PMID- 28762928
TI  - [Eosinophilic Necrotizing Myocarditis Complicated by Myocardial Rupture].
AB  - In this female patient eosinophilic myocarditis was complicated by myocardial
      rupture and hemopericardium with cardiac tamponade. Special features of this case
      were old age of the patient, fulminant course of the disease, myocardial
      infarction-like ECG changes, absence of peripheral blood eosinophilia.
      Presentation is accompanied by discussion of issues of epidemiology, clinical
      course, diagnostics, and possible causes of eosinophilic myocarditis.

PMID- 28762929
TI  - [Risk Factors of Cardiovascular Complications After Beating-Heart Coronary Artery
      Bypass Grafting in Patients With Type Two Diabetes].
AB  - AIM: to determine risk factors of early cardiovascular complications after
      beating-heart coronary artery bypass grafting (CABG) in patients with ischemic
      coronary disease (IHD) and type two diabetes (D2). MATERIALS AND METHODS: We
      included into this study 188 patients (mean age 59 years, 85.1% men) with IHD and
      D2 who underwent off-pump CABG. The following cardiovascular complications (CVC)
      registered within 7 days after surgery were analyzed: myocardial infarction (MI),
      stroke/transient ischemic attack (S/TIA), atrial fibrillation (AF). The control
      group of patients without CVC was formed by case-control method. In the study
      groups we compared IHD severity, coronary angiography, brachiocephalic and
      peripheral arteries duplex ultrasonography data, blood pressure level, glomerular
      filtration rate, EuroSCORE II risk, preoperative glycemic parameters and
      hypoglycemic therapy, as well as CABG volume and severity. Factors associated
      with postoperative CVC were determined by multiple stepwise logistic regression.
      RESULTS AND CONCLUSIONS: CVC were registered in 47 patients (MI - in 18, S/TIA -
      in 2, AF - in 27). As compared with the control group patients with CVC had
      higher Canadian Cardiovascular Society angina class and EuroSCORE II risk, lower
      left ventricular ejection fraction and glomerular filtration rate; they more
      frequently had left main coronary artery involvement, total coronary artery
      occlusions, carotid and peripheral artery disease. Group of patients with CVC had
      higher levels of glycosylated hemoglobin, serum glucose and its diurnal
      variability, as well as higher proportion of patients switched preoperatively
      from oral hypoglycemic agents to rapid-acting insulin. According to logistic
      regression most informative predictors of CVC were peripheral artery disease
      (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.7-7.1), diurnal serum
      glucose variability on admission day (OR 13.2, 95% CI 5.9-30.0 per 0.1 mmol/l)
      and the day before surgery (OR 1.3, 95%CI 1.2-2.4 per 0.1 mmol/l), and switching
      from oral hypoglycemic agents to insulin (OR 2.5, 95%CI 1.2-5.5).

PMID- 28762930
TI  - [The Complex Program of Rehabilitation of Patients With Ischemic Heart Disease
      After Coronary Artery Bypass Surgery in Ambulatory Cardiorehabilitational
      Department: Clinical Effects of Third Stage of Rehabilitation].
AB  - PURPOSE: to assess clinical efficacy of early post discharge rehabilitation of
      patients with ischemic heart disease (IHD) after coronary artery bypass grafting
      (CABG) in conditions of a polyclinical department of cardiological rehabilitation
      (stage III of cardiorehabilitation). MATERIAL AND METHODS: We included in this
      study 36 men with IHD in 3-8 weeks (mean 7.8+/-1.6 weeks) after CABG. Patients
      were randomized in 2groups: patients of the main group attended special "School
      for patients recovering after CABG" [School] (60-80 min sessions once a week for
      5 weeks) and participated in a program of monitored (up to 60 min 3 times a week
      for 4 months) and unmonitored (home based) exercise training. Patients of the
      control group attended School and were given advice to do physical exercises at
      home. Follow up duration was 1 year. RESULTS: Main group. Compared with baseline
      values after 4 months exercise duration increased 32.6% (p<0.05), this effect
      persisted at 12 month; threshold exercise load increased 35.2% (p<0.05) after 4,
      53.9% after 6, and 49.5% after 12 month. After 4 and 12 months of training some
      increases of left ventricular (LV) ejection fraction and stroke volume, and
      decrease of LV end systolic volume occurred. Physical training in this group was
      associated with improvement of parameters of quality of life. During 12 months of
      follow up there were no significant changes of concentrations of total and low
      density lipoprotein cholesterol (TC, LDLC). In the control group slight increase
      of exercise duration was observed only at 12 months (9.8%, p<0.05), and it was
      not accompanied by dynamics of exercise tolerance. Increases of concentrations of
      TC (10.2%, p<0.05) and LDLC (15.6%, p<0.05) were registered at 12 months. Serious
      cardiovascular complications in the main group (physical training + educational
      School) were three times less frequent than in the control group (attendance of
      School only) (11.1 vs. 39.2%, respectively.

PMID- 28762931
TI  - [Effect of Bisoprolol on Heart Rate Variability in Patients With Coronary
      Atherosclerosis: Dependence on Polymorphisms of -1 Adrenergic Receptor Gene].
AB  - PURPOSE: To assess effectiveness of a -blocker bisoprolol basing on a study of
      variability of cardiac rhythm and polymorphism of -1 adrenergic receptor gene
      (ADRB1). MATERIAL AND METHODS: We examined 99 patients with coronary
      atherosclerosis either with stable angina without history of vascular events or
      more than 6 month after myocardial infarction and/or coronary intervention.
      RESULTS AND CONCLUSION: Patients with coronary atherosclerosis including those
      after myocardial infarction had signs of autonomic dysfunction regardless of the
      presence of genetic polymorphism Gly389Arg ADRB1. Sympathetic influences at
      orthostatic test performed during taking bisoprolol were more pronounced in
      patients with Gly389Gly ADRB1 genotype than in patients with Gly389Arg ADRB1
      genotype. Basing on this observation we conclude that the control by bisoprolol
      of heart rate regulation in patients with Gly389Gly ADRB1 genotype should be
      considered inadequate.

PMID- 28762932
TI  - [Results of a Randomized Study: Multivessel Stenting and Staged Revascularization
      in Patients With ST-Elevation Myocardial Infarction Using Second Generation Drug
      Covered Stents].
AB  - Lack of evidence base on the use of 2-nd generation drug covered stents in
      patients with ST-elevation myocardial infarction (STEMI) with multivessel lesions
      in coronary vascular bed makes it important to conduct studies of new devices in
      a framework of multivessel stenting in primary percutaneous coronary intervention
      (PPCI) and staged revascularization. Controversial data on outcomes of the
      strategy of multiple revascularization in STEMI might be related to the use of
      previous generation coronary stents in this category of patients. Aim of this
      study was assessment of one year outcomes of multivessel stenting in a framework
      of PPCI and staged revascularization (8.6+/-4.2 days between stages) with the use
      of 2-nd generation drug covered stents. We showed that both multivessel stenting
      and staged revascularuzation might be effective options of revascularization in
      STEMI with the use of 2-nd generation drug covered stents and maintenance of
      limited time interval between PCI on infarct related artery and PCI on other
      coronary vessels with significant stenotic lesions. This strategy was associated
      with low rate of adverse cardiovascular events.

PMID- 28762933
TI  - [Optimization of BP Control and Arterial Elasticity With Fixed Combination
      Therapy Perindopril and Amlodipine In Patients With Arterial Hypertension and
      Increased Pulse Wave Velocity].
AB  - : The aim of the study was to assess the possibility of fixed combination
      perindopril+amlodipine to improve arterial elesticity in patients with
      hypertension and high pulse wave velocity, despite previous combination
      antihypertensive therapy. In an open, multicenter, observational study duration
      of 24 weeks 80 patients were included, divided into 4 equal-sized groups,
      depending on initial antihypertensive therapy: Group 1 - the combination of ACE
      inhibitor and diuretic, Group 2 - the combination of ACE inhibitor and calcium
      channel blocker, Group 3 - the combination of diuretic and angiotensin receptor
      blocker, Group 4 - the combination of angiotensin receptor blocker and calcium
      antagonist. All patients underwent ambulatory BP monitoring, applanation
      tonometry (assessment of augmentation index and central blood pressure), pulse
      wave velocity measurement. According to the office BP measurements fixed
      combination perindopril+amlodipine provided the SBP reduction by 17.5%, 15.6%,
      15, 6%, 15.5% and 17.7%, DBP reduction by 14.6%, 12.9%, 13.8%, respectively, in
      groups ACEI+D initial combination therapy, ACEI+AC initial combination therapy,
      ARB+D initial combination therapy, ARB+AC initial combination therapy. According
      ABPM data SBP has been decreased by 12.2%, 12.4%, 11.3%, 12.6% and DBP by 14.3%,
      11.1%, 8.9%, 12.6%. The fixed combination perindopril+amlodipine reduced PWV by
      25.2%, 21.6%, 23.1%, 23.0%, augmentation index by 43.4%, 48.9%, 41.5%, 38.3%,
      central SBP by 16.1%, 15.5%, 14.4%, 15.2%, the central DBP by 15.1%, 13.8%,
      13.8%, 18.0% (p<0.01 vs. baseline). CONCLUSIONS: Fixed combination
      perindopril+amlodipine provides goal blood pressure control, improves arterial
      elasticity indexes (augmentation index, PWV, central blood pressure). Additional
      properties include reduction of BMI and lipid metabolism improving in patients
      initially treated with a combination antihypertensive therapy.

PMID- 28762934
TI  - [Diagnostic Value of Biochemical Markers in Patients With Chronic Heart Failure
      With Reduced, Borderline and Preserved Left Ventricular Ejection Fraction].
AB  - PURPOSE OF THE STUDY: The study of the diagnostic value of biochemical markers of
      myocardial stress and inflammation in chronic heart failure (CHF) with different
      values of the ejection fraction (EF) of the left ventricle (LV). MATERIAL AND
      METHODS: The cross-sectional study included 105 patients aged 24 to 84 years
      (mean 58+/-14 years) with stable chronic heart failure I-II NYHA functional class
      classification. The causes of CHF were ischemic heart disease (IHD) in 33% of
      patients and arterial hypertension (AH) - 67%. All patients received medical
      treatment: angiotensin-converting enzyme (ACE) - 76%, -blockers - 72%, diuretics 
      100%, statins - 80%. The control group consisted of 35 healthy volunteers. All
      subjects identified blood natriuretic peptide (NT-proBNP, ANP), adiponectin,
      galectin-3, pentraxins-3 and growth differentiation factor-15 (GDF-15) by enzyme
      immunoassay (ELISA). All surveyed performed transthoracic echocardiography
      (Echo). RESULTS: The blood NT-proBNP, ANP, galectin-3, pentraxins and GDF-3-15 in
      patients with chronic heart failure was significantly higher than in the control
      group (p<0.001 in all cases). In contrast, the level of adiponectin was
      significantly higher than in healthy individuals - 11.90 (11.39; 12.65) vs 7.73
      (3.58; 8.86) ng/ml in patients with chronic heart failure (p<0.001). LVEF ranged
      from 30 to 55%, in 33% of patients it was >50%. Correlation analysis Spearman
      found strong correlations (p<0.001 for all markers) between LVEF and the content
      of all the biomarkers, while between the PV and the level of adiponectin is a
      positive correlation was found (r=0.862), and between the PV and the other
      biomarkers - reverse (r from -0.858 to -0.901). Multivariate linear regression
      analysis found the strongest correlation with the value of LVEF at pentraxin 3
      and adiponectin. Subsequent ROC-analysis confirmed the diagnostic value of
      adiponectin in patients with heart failure and preserved ejection fraction. Thus,
      the level of adiponectin more than 8.3 ng/ml served as a prognostic factor for
      the presence of heart failure in patients with LVEF >50% with a sensitivity of
      94.3% and a specificity of 92.9% (area under the curve 0.977; 95% confidence
      interval from 0.954 to 0.999; p<0.001). CONCLUSIONS: Among the 6 studied
      biomarkers of myocardial stress and inflammation only adiponectin has diagnostic
      significance in patients with heart failure and preserved ejection fraction.

PMID- 28762935
TI  - [Galectin-3, Markers of Oxidative Stress and Renal Dysfunction in Patients With
      Chronic Heart Failure].
AB  - OBJECTIVE: to determine levels of galectin-3, markers of renal dysfunction, and
      plasma oxidative stress; to assess their correlation in patients with chronic
      heart failure (CHF) of various severity. MATERIAL AND METHODS: We included in
      this study 157 CHF patients (with documented prior myocardial infarction.
      Patients were divided into 3 groups according to their NYHA functional class
      (group 1 - class II n=60, group 2 - class III n=52, group 3 - class IV n=45). All
      patients underwent clinical examination, echocardiography. Laboratory parameters
      included measurement of plasma levels of galectin-3, NT-proBNP, as well as
      markers of oxidative stress (oxidized low density lipoprotein cholesterol
      [oxLDLC], SH-groups) and renal dysfunction (creatinine, uric acid, cystatin-C).
      RESULTS: The level of galectin-3 (median) in groups 1, 2, and 3 was 10, 19 and 38
      ng/ml respectively. There were significant differences between groups (p<0,001).
      In all groups levels of galectin-3 significantly (p<0.01) correlated with those
      of oxLDL (positively) and SH-groups (negatively): r1=0.52, r2=0.59, r3=0.63,
      p<0.01, and r1=-0.58, r2=-0.65, r3=-0.71, respectively. Correlation analysis also
      revealed close and moderate correlations between galectin-3 and cystatin-C,
      glomerular filtration rate, and uric acid. CONCLUSIONS: In patients with CHF and
      prior myocardial infarction plasma concentration of galectin-3 was associated
      with severity of CHF and significantly correlated with markers of renal
      dysfunction and plasma oxidative stress.

PMID- 28762936
TI  - [The Phenotype of Chronic Obstructive Pulmonary Disease With Frequent
      Exacerbations in the Aspect of Long-term Percutaneous Coronary Intervention
      Results].
AB  - OBJECTIVE: To evaluate the results of percutaneous coronary interventions (PCI)
      in patients with coronary heart disease (CHD) and chronic obstructive pulmonary
      disease (COPD), depending on the frequency of exacerbations of COPD. MATERIALS
      AND METHODS: We enrolled in this prospective study 103 patients with CHD and COPD
      who underwent PCI (n=103) including 25 who satisfied criteria of COPD phenotype
      with frequent exacerbations (main group). Analysis included comparison of rates
      and times to major adverse cardiac events (MACE - myocardial infarction, stroke,
      cardiac death, repeat revascularization) in the main group and other patients.
      Clinical and functional features of patients with major adverse cardiac events
      were also analyzed. RESULTS: Study groups did not differ significantly on
      demographic characteristics and the presence of comorbidity. MACE frequency was
      almost 2 times higher in the main group (relative risk 1.87; 95% confidence
      interval (CI) 1.1-3.3). There was a tendency to higher rate of MACE among
      patients with history of more or equal 1 COPD exacerbations in a year (40% vs.
      24%, p=0.09). The following clinical and functional characteristics of COPD, were
      associated with MACE in remote period after PCI: frequency of exacerbations,
      results of the COPD Assessment Test, exercise capacity, forced expiratory volume
      in 1 sec. Conclusion/ COPD phenotype with frequent exacerbations in patients with
      CHD undergoing PCI is associated with increased risk and earlier occurrence of
      MACE.

PMID- 28762938
TI  - [In memory of Alexey Petrovich Golikov].

PMID- 28762937
TI  - [Risk of Cardiovascular Complications and Geriatric Syndromes Among Elderly
      Women].
AB  - AIM: to assess the prevalence of some geriatric syndromes and their association
      with high risk of cardiovascular complications (RCVC) among elderly women.
      MATERIAL AND METHODS: We examined 72 women aged 69-77 years with cardiovascular
      diseases. Examination included laboratory and echocardiography assessment, dual
      energy X-ray absorptiometry, 6-min walk test, assessment of psycho-emotional
      status using Mini-mental State Examination (MMSE) questionnaire. Frailty was
      defined as three or more of the following: weight loss, low physical activity
      levels, MMSE less or equal 23 points, weakness (chair stand test>10 sec), history
      of multiple falls. Follow up was 7.3 (5.5-7.8) months. RESULTS: High CVR was
      found in 70.8% women: in 59.1% women aged 65-74 years and in 89.3% - aged more or
      equal 75 years, =0.006. Osteoporosis (OP) was found in 51.3% women aged 65-74 and
      in 90.5% - aged more or equal 75 years, =0.024; MMSE was 27 (24-28) vs 24 (20-26)
      points, respectively, =0.008. The geriatric syndrome of frailty was found in
      13.6% women aged 65-74 and in 64.3% - aged more or equal 75 years. Frailty was
      associated with high CVR (odds ratio [R] 7.2, 95% confidence interval [CI] 1.5
      34.2, =0.013), chronic kidney disease (CKD, R 18.9, 95%CI 5.2-20.2, <0.001), P (R
      4.5, 95%CI 1.3-15.8, =0.019), history of myocardial infarction (MI, R 6.8, 95%CI
      2.2-20.8, =0.001), greater age (R 6.0, 95%CI 2.1-17.5, =0.001). CONCLUSION: High
      CVR was prevalent among greater age women what could be explained by prevalence
      of chronic heart failure, atrial fibrillation, CKD. Prevalence of frailty was
      13.6 and 64.3% among women aged 65-74 and more or equal 75years, respectively. It
      was significantly associated with high CVR, OP, PMI, CKD.

PMID- 28762940
TI  - [Mitral Regurgitation: Etiopathogenic Mechanisms and Review of Diagnostic
      Methods].

PMID- 28762939
TI  - [A New Insight on Anti-Ischemic Action of Ivabradine in Patients With Stable
      Angina].
AB  - Increase in heart rate triggers most ischemic episodes due to disbalance between
      myocardial oxygen delivery and consumption. Furthermore, increased heart rate is
      a modifiable risk factor in patients with chronic heart failure. Ivabradine
      reduces heart rate by selectively inhibiting the If current of sinoatrial node
      cells. Recent studies have shown that ivabradine may reduce myocardial ischaemia
      and its consequences not only through heart rate reduction, but also because of
      additional pleiotropic effects. This review summarizes last findings that
      demonstrate variety of ivabradine actions on coronary blood flow and left
      ventricular function in patients with ischemic heart disease.

PMID- 28762941
TI  - [Rational Choice of Anticoagulant Therapy in Patients With Idiopathic and
      Provoked Venous Thromboembolism].

PMID- 28762942
TI  - [Recommendations of the European Society of Cardiology and the European
      Atherosclerosis Society on Cardiovascular Disease Prevention and Management of
      Dyslipidemias. for the Diagnosis of Atherosclerosis and Dyslipidemia Treatment
      (2016): Basic S.G.]
AB  - This review summarizes the main provisions of the new, issued in 2016,
      recommendations of the European Society of Cardiology and Atherosclerosis Society
      in cooperation with the European Association on Cardiovascular Prevention and
      Rehabilitation on Cardiovascular disease prevention and Management of
      dyslipidemia. In these recommendations, the following trends can be traced
      distinctly: priority in primary prevention is given to non-drug methods of
      influence; targets of hypolipidemic therapy are identified not only for low
      density lipoprotein (LDL) cholesterol (CH), but also for non-high density
      lipoprotein (HDL) CH, especially in cases of concomitant hypertriglyceridemia. In
      the field of therapy, in which statins remain the main tool of correction of
      hyperlipidemia, it is recommended to more widely resort to the use of combination
      therapy, especially in cases of familial hypercholesterolemia or intolerance to
      statins; introduction of a new class of drugs- inhibitors of proprotein
      convertase subtilisin/kexin type 9 makes it possible to further reduce the level
      of LDLCH, lipoprotein(a) more than 60%. Regarding the wider application of these
      drugs there are issues related to the relatively limited experience of their use
      and the lack of data on long-term results and the incidence of side effects. Much
      attention is paid to more active correction of dyslipidemia in elderly patients,
      patients with chronic renal failure, diabetes, and several other diseases. The
      emergence of new European recommendations will undoubtedly serve as a stimulus to
      the revision of the Russian recommendations, which remain unchanged from 2012.

PMID- 28762943
TI  - [Review of International Clinical Trials in the Field of Cardiology Reported in
      2016].
AB  - We present in this article the review of 6 scientific Hot Line sessions of the
      2016 European Congress of Cardiology devoted to novel approaches to treatment of
      heart failure, strategies of prevention of complications of cardiovascular
      diseases, dyslipidemia, imaging methods of investigation, and stenting in
      coronary heart disease.

PMID- 28762944
TI  - Synaptic plasticity through activation of GluA3-containing AMPA-receptors.
AB  - Excitatory synaptic transmission is mediated by AMPA-type glutamate receptors
      (AMPARs). In CA1 pyramidal neurons of the hippocampus two types of AMPARs
      predominate: those that contain subunits GluA1 and GluA2 (GluA1/2), and those
      that contain GluA2 and GluA3 (GluA2/3). Whereas subunits GluA1 and GluA2 have
      been extensively studied, the contribution of GluA3 to synapse physiology has
      remained unclear. Here we show in mice that GluA2/3s are in a low-conductance
      state under basal conditions, and although present at synapses they contribute
      little to synaptic currents. When intracellular cyclic AMP (cAMP) levels rise,
      GluA2/3 channels shift to a high-conductance state, leading to synaptic
      potentiation. This cAMP-driven synaptic potentiation requires the activation of
      both protein kinase A (PKA) and the GTPase Ras, and is induced upon the
      activation of beta-adrenergic receptors. Together, these experiments reveal a
      novel type of plasticity at CA1 hippocampal synapses that is expressed by the
      activation of GluA3-containing AMPARs.

PMID- 28762945
TI  - Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms.
AB  - Biofilm formation is critical for the infection cycle of Vibrio cholerae. Vibrio
      exopolysaccharides (VPS) and the matrix proteins RbmA, Bap1 and RbmC are required
      for the development of biofilm architecture. We demonstrate that RbmA binds VPS
      directly and uses a binary structural switch within its first fibronectin type
      III (FnIII-1) domain to control RbmA structural dynamics and the formation of VPS
      dependent higher-order structures. The structural switch in FnIII-1 regulates
      interactions in trans with the FnIII-2 domain, leading to open (monomeric) or
      closed (dimeric) interfaces. The ability of RbmA to switch between open and
      closed states is important for V. cholerae biofilm formation, as RbmA variants
      with switches that are locked in either of the two states lead to biofilms with
      altered architecture and structural integrity.

PMID- 28762948
TI  - Previous Atorvastatin Treatment and Risk of Diabetic Foot Infection in Adult
      Patients: A Case-control Study.
AB  - OBJECTIVE: In addition to their lipid-lowering abilities, statins have anti
      inflammatory and immunomodulatory properties. Increasing recent evidence suggests
      the possible role of pretreatment with statins in preventing or decreasing
      morbidity and mortality from infection. Diabetic foot infection (DFI) is a common
      complication of diabetes mellitus. The aim of this study was to determine whether
      previous atorvastatin use is associated with reduced risk of DFI and better
      outcomes of these infections. MATERIALS AND METHODS: One hundred ten adult
      patients admitted with a diagnosis of DFI were enrolled in the experimental
      group. For the control group, 123 adult patients with diabetes mellitus in an
      outpatient setting and without a history of DFIs were accepted. Participants in
      both groups were classified as statin users or non-statin users depending on
      history of atorvastatin treatment. For all individuals, the demographic,
      clinical, and laboratory findings were registered. RESULTS: Atorvastatin was used
      in 49.1% of the experimental group cases and in 66.7% of the control, and it
      showed a statistically significant difference (P = .007). Logistic regression
      analysis also showed that previous atorvastatin use significantly reduces the
      risk of DFI (odds ratio = 0.36; 95% confidence interval, 0.19-0.71; P = .003).
      Severe DFI, bone involvement, and the need for surgical intervention was lower in
      the experimental group, but this difference was not statistically significant.
      CONCLUSION: Prior therapy with atorvastatin considerably reduces the onset of
      DFIs. In addition to other effects, statins may be useful in preventing DFIs.

PMID- 28762946
TI  - Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin
      neurons.
AB  - POMC neurons integrate metabolic signals from the periphery. Here, we show in
      mice that food deprivation induces a linear current-voltage relationship of AMPAR
      mediated excitatory postsynaptic currents (EPSCs) in POMC neurons. Inhibition of
      EPSCs by IEM-1460, an antagonist of calcium-permeable (Cp) AMPARs, diminished
      EPSC amplitude in the fed but not in the fasted state, suggesting entry of GluR2
      subunits into the AMPA receptor complex during food deprivation. Accordingly,
      removal of extracellular calcium from ACSF decreased the amplitude of mEPSCs in
      the fed but not the fasted state. Ten days of high-fat diet exposure, which was
      accompanied by elevated leptin levels and increased POMC neuronal activity,
      resulted in increased expression of Cp-AMPARs on POMC neurons. Altogether, our
      results show that entry of calcium via Cp-AMPARs is inherent to activation of
      POMC neurons, which may underlie a vulnerability of these neurons to calcium
      overload while activated in a sustained manner during over-nutrition.

PMID- 28762949
TI  - Laser Doppler Flowmetry and Transcutaneous Oximetry in Chronic Skin Ulcers: A
      Comparative Evaluation.
AB  - INTRODUCTION/OBJECTIVE: Laser Doppler Flowmetry (LDF) and transcutaneous oximetry
      (TcpO2) are established methods for investigating cutaneous perfusion. To date,
      no study previously performed has compared data obtained from these 2
      methodologies in cases of chronic cutaneous ulcers. MATERIALS AND METHODS: Laser
      Doppler Flowmetry and TcpO2 were performed in 25 consecutive outpatients with
      chronic lower limb ulcers (group A, experimental; 9 women and 16 men; mean age 67
      years [range, 52-81 years]) and 25 age- and sex-matched healthy control subjects
      (group B, control) enrolled for the study. Ulcer aetiologies included 12
      peripheral arterial occlusive disease, 9 chronic venous insufficiencies, and 4
      pressure ulcers. Data were analyzed with Shapiro-Wilk and Wilcoxon-Mann-Whitney
      tests. RESULTS: A statistically significant difference (P < .05) was found
      between LDF values of the 2 groups. No statistically significant differences were
      found between the 2 groups regarding the TcpO2 measurements. CONCLUSION: The data
      confirmed the soundness of LDF while investigating local perfusion in patients
      with chronic cutaneous ulcers. The same diagnostic accuracy was not obtained by
      means of TcpO2.

PMID- 28762955
TI  - Perpendicularly magnetized Co20Fe60B20 layer sandwiched between Au with low
      Gilbert damping.
AB  - Nowadays, the CoFeB thin layered film is intensively studied because of its
      potential applications in spintronic devices, especially devices based on spin
      transfer torque phenomena. Hitherto, it has been shown that CoFeB may possess
      perpendicular magnetic anisotropy (PMA) when it is sandwiched between different
      layers (e.g. MgO, Pt, Pd, Ta, W). However, there is no experimental evidence that
      CoFeB, sandwiched between Au layers, has strong PMA. Moreover, in comparison with
      other noble metals, Au-based film systems exhibit the smallest spin pumping
      effect, which provides the main contribution to the damping in thin films in
      contact with heavy metals. Therefore, Au/CoFeB/Au may be a good candidate for
      future applications, where perpendicular magnetic anisotropy and low damping are
      required. Here, we show that PMA and low damping can be achieved in a Au/CoFeB/Au
      system without annealing.

PMID- 28762947
TI  - Energy imbalance alters Ca2+ handling and excitability of POMC neurons.
AB  - Satiety-signaling, pro-opiomelanocortin (POMC)-expressing neurons in the arcuate
      nucleus of the hypothalamus play a pivotal role in the regulation of energy
      homeostasis. Recent studies reported altered mitochondrial dynamics and decreased
      mitochondria- endoplasmic reticulum contacts in POMC neurons during diet-induced
      obesity. Since mitochondria play a crucial role in Ca2+ signaling, we
      investigated whether obesity alters Ca2+ handling of these neurons in mice. In
      diet-induced obesity, cellular Ca2+ handling properties including mitochondrial
      Ca2+ uptake capacity are impaired, and an increased resting level of free
      intracellular Ca2+ is accompanied by a marked decrease in neuronal excitability.
      Experimentally increasing or decreasing intracellular Ca2+ concentrations
      reproduced electrophysiological properties observed in diet-induced obesity.
      Taken together, we provide the first direct evidence for a diet-dependent
      deterioration of Ca2+ homeostasis in POMC neurons during obesity development
      resulting in impaired function of these critical energy homeostasis-regulating
      neurons.

PMID- 28762956
TI  - Non-conservative optical forces.
AB  - Undoubtedly, laser tweezers are the most recognized application of optically
      induced mechanical action. Their operation is usually described in terms of
      conservative forces originating from intensity gradients. However, the
      fundamental optical action on matter is non-conservative. We will review
      different manifestations of non-conservative optical forces (NCF) and discuss
      their dependence on the specific spatial properties of optical fields that
      generate them. New developments relevant to the NCF such as tractor beams and
      transversal forces are also discussed.

PMID- 28762958
TI  - Photo-electrochemical properties of graphene wrapped hierarchically branched
      nanostructures obtained through hydrothermally transformed TiO2 nanotubes.
AB  - Hierarchically structured nanomaterials play an important role in both light
      absorption and separation of photo-generated charges. In the present study,
      hierarchically branched TiO2 nanostructures (HB-MLNTs) are obtained through
      hydrothermal transformation of electrochemically anodized TiO2 multi-leg
      nanotubes (MLNT) arrays. Photo-anodes based on HB-MLNTs demonstrated 5 fold
      increase in applied bias to photo-conversion efficiency (%ABPE) over that of TiO2
      MLNTs without branches. Further, such nanostructures are wrapped with reduced
      graphene oxide (rGO) films to enhance the charge separation, which resulted in
      ~6.5 times enhancement in %ABPE over that of bare MLNTs. We estimated charge
      transport (eta tr) and charge transfer (eta ct) efficiencies by analyzing the
      photo-current data. The ultra-fine nano branches grown on the MLNTs are effective
      in increasing light absorption through multiple scattering and improving charge
      transport/transfer efficiencies by enlarging semiconductor/electrolyte interface
      area. The charge transfer resistance, interfacial capacitance and electron decay
      time have been estimated through electrochemical impedance measurements which
      correlate with the results obtained from photocurrent measurements.

PMID- 28762959
TI  - Mechanical properties and cell-culture characteristics of a polycaprolactone
      kagome-structure scaffold fabricated by a precision extruding deposition system.
AB  - To enhance the mechanical properties of three-dimensional (3D) scaffolds used for
      bone regeneration in tissue engineering, many researchers have studied their
      structure and chemistry. In the structural engineering field, the kagome
      structure has been known to have an excellent relative strength. In this study,
      to enhance the mechanical properties of a synthetic polymer scaffold used for
      tissue engineering, we applied the 3D kagome structure to a porous scaffold for
      bone regeneration. Prior to fabricating the biocompatible-polymer scaffold, the
      ideal kagome structure, which was manufactured by a 3D printer of the digital
      light processing type, was compared with a grid-structure, which was used as the
      control group, using a compressive experiment. A polycaprolactone (PCL) kagome
      structure scaffold was successfully fabricated by additive manufacturing using a
      3D printer with a precision extruding deposition head. To assess the physical
      characteristics of the fabricated PCL-kagome-structure scaffold, we analyzed its
      porosity, pore size, morphological structure, surface roughness, compressive
      stiffness, and mechanical bending properties. The results showed that, the
      mechanical properties of proposed kagome-structure scaffold were superior to
      those of a grid-structure scaffold. Moreover, Sarcoma osteogenic (Saos-2) cells
      were used to evaluate the characteristics of in vitro cell proliferation. We
      carried out cell counting kit-8 (CCK-8) and DNA contents assays. Consequently,
      the cell proliferation of the kagome-structure scaffold was increased; this could
      be because the surface roughness of the kagome-structure scaffold enhances
      initial cell attachment.

PMID- 28762957
TI  - Integrating three-dimensional printing and nanotechnology for musculoskeletal
      regeneration.
AB  - The field of tissue engineering is advancing steadily, partly due to advancements
      in rapid prototyping technology. Even with increasing focus, successful complex
      tissue regeneration of vascularized bone, cartilage and the osteochondral
      interface remains largely illusive. This review examines current three
      dimensional printing techniques and their application towards bone, cartilage and
      osteochondral regeneration. The importance of, and benefit to, nanomaterial
      integration is also highlighted with recent published examples. Early-stage
      successes and challenges of recent studies are discussed, with an outlook to
      future research in the related areas.

PMID- 28762960
TI  - Zinc and strontium based phosphate glass beads: a novel material for bone tissue
      engineering.
AB  - Degradable phosphate-based glasses that contain strontium, zinc and calcium were
      investigated to examine their function as an osteoconductive material. Glass
      beads of the general formula of (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) or (ZnO) were
      prepared by a melt quench technique followed by milling and spheroidisation.
      After performing x-ray diffraction on all the samples for glass structure
      evaluation, glass bead size distribution was initially measured by a scanning
      electron microscope (SEM). Then, some of these samples were immersed in deionised
      water to evaluate both the surface changes and measure the ion release rate,
      whereas other samples of glass beads were incubated in culture media to determine
      pH changes. Furthermore, human osteoblast-like osteosarcoma cells MG63 and human
      mesenchymal stem cells were seeded on the glass beads to determine their
      cytocompatibility via applying CCK assay, ALP assay and Ca assay. SEM images and
      fluorescence images of confocal microscopy were performed for the cellular
      studies. While mass degradation and ion release results displayed a significant
      increase with zinc and strontium incorporation within time, pH results showed an
      initial increase in pH followed by a decrease. Cellular studies emphasised that
      all formulations enhanced cellular proliferation. Phosphate glass beads with zinc
      content 5 mol% and strontium content of 17.5 mol%, (ZnO5) and (SrO17.5)
      respectively displayed more promising results although they were insignificantly
      different from that of control (p > 0.05). This may suggest their applicability
      in hard tissue engineering.

PMID- 28762961
TI  - Endothelial cell responses to castor oil-based polyurethane substrates
      functionalized by direct laser ablation.
AB  - Surface-induced thrombosis and lack of endothelialization are major drawbacks
      that hamper the widespread application of polyurethanes for the fabrication of
      implantable cardiovascular devices. Endothelialization of the blood-contacting
      surfaces of these devices may avoid thrombus formation and may be implemented by
      strategies that introduce micro and submicron patterns that favor adhesion and
      growth of endothelial cells. In this study, we used laser radiation to directly
      introduce topographical patterns in the low micrometer range on castor oil-based
      polyurethane, which is currently employed to fabricate cardiovascular devices. We
      have investigated cell adhesion, proliferation, morphology and alignment in
      response to these topographies. Reported results show that line-like and pillar
      like patterns improved adhesion and proliferation rate of cultured endothelial
      cells. The line-like pattern with 1 MUm groove periodicity was the most efficient
      to enhance cell adhesion and induced marked polarization and alignment. Our study
      suggests the viability of using laser radiation to functionalize PU-based
      implants by the introduction of specific microtopography to facilitate the
      development of a functional endothelium on target surfaces.

PMID- 28762964
TI  - Accurate charge densities from powder X-ray diffraction - a new version of the
      Aarhus vacuum imaging-plate diffractometer.
AB  - In recent years powder X-ray diffraction has proven to be a valuable alternative
      to single-crystal X-ray diffraction for determining electron-density
      distributions in high-symmetry inorganic materials, including subtle deformation
      in the core electron density. This was made possible by performing diffraction
      measurements in vacuum using high-energy X-rays at a synchrotron-radiation
      facility. Here we present a new version of our custom-built in-vacuum powder
      diffractometer with the sample-to-detector distance increased by a factor of
      four. In practice this is found to give a reduction in instrumental peak
      broadening by approximately a factor of three and a large improvement in signal
      to-background ratio compared to the previous instrument. Structure factors of
      silicon at room temperature are extracted using a combined multipole-Rietveld
      procedure and compared with ab initio calculations and the results from the
      previous diffractometer. Despite some remaining issues regarding peak asymmetry,
      the new diffractometer yields structure factors of comparable accuracy to the
      previous diffractometer at low angles and improved accuracy at high angles. The
      high quality of the structure factors is further assessed by modelling of core
      electron deformation with results in good agreement with previous investigations.

PMID- 28762965
TI  - Experimental charge-density studies: data reduction and model quality: the more
      the better?
AB  - In this review, recent developments concerning data and model quality in
      experimental charge-density investigations from a personal view-point are
      described. Data quality is not only achieved by the high resolution, high
      I/sigma(I) values, low merging R values and high multiplicity. The quality of the
      innermost reflections especially is crucial for mapping the density distribution
      of the outermost valence electrons and can be monitored by (I/sigma)asymptotic.
      New detector technologies seem to be promising improvements. Empirical
      corrections to correct for low-energy contamination of mirror-focused X-ray data
      and for resolution- and temperature-dependent errors caused by factors such as
      thermal diffuse scattering are described. Shashlik-like residual density patterns
      can indicate the need for an anharmonic description of the thermal motion of
      individual atoms. The physical reliability of the derived model must be
      thoroughly analysed. The derived probability density functions for the mean
      squared atomic vibrational displacements especially should have only small
      negative values. The treatment of H atoms has been improved by methods to
      estimate anisotropic thermal motion. For very high resolution data, the
      polarization of the core density cannot be neglected. Several tools to detect
      systematic errors are described. A validation tool is presented that easily
      detects when the refinement of additional parameters yields a real improvement in
      the model or simply overfits the given data. In all investigated structures, it
      is proved that the multipole parameters of atoms with a comparable chemical
      environment should be constrained to be identical. The use of restraints could be
      a promising alternative.

PMID- 28762966
TI  - When combined X-ray and polarized neutron diffraction data challenge high-level
      calculations: spin-resolved electron density of an organic radical.
AB  - Joint refinement of X-ray and polarized neutron diffraction data has been carried
      out in order to determine charge and spin density distributions simultaneously in
      the nitronyl nitroxide (NN) free radical Nit(SMe)Ph. For comparison purposes,
      density functional theory (DFT) and complete active-space self-consistent field
      (CASSCF) theoretical calculations were also performed. Experimentally derived
      charge and spin densities show significant differences between the two NO groups
      of the NN function that are not observed from DFT theoretical calculations. On
      the contrary, CASSCF calculations exhibit the same fine details as observed in
      spin-resolved joint refinement and a clear asymmetry between the two NO groups.

PMID- 28762967
TI  - Multi-temperature study of potassium uridine-5'-monophosphate: electron density
      distribution and anharmonic motion modelling.
AB  - Uridine, a nucleoside formed of a uracil fragment attached to a ribose ring via a
      beta-N1-glycosidic bond, is one of the four basic components of ribonucleic acid.
      Here a new anhydrous structure and experimental charge density distribution
      analysis of a uridine-5'-monophosphate potassium salt, K(UMPH), is reported. The
      studied case constitutes the very first structure of a 5'-nucleotide potassium
      salt according to the Cambridge Structural Database. The excellent crystal
      quality allowed the collection of charge density data at various temperatures,
      i.e. 10, 100, 200 and 300 K on one single crystal. Crystal structure and charge
      density data were analysed thoroughly in the context of related literature
      reported examples. Detailed analysis of the charge density distribution revealed
      elevated anharmonic motion of part of the uracil ring moiety relatively weakly
      interacting with the neighbouring species. The effect was manifested by alternate
      positive and negative residual density patterns observed for these atoms, which
      'disappear' at low temperature. It also occurred that the potassium cation, quite
      uniformly coordinated by seven O atoms from all molecular fragments of the UMPH-
      anion, including the O atom from the ribofuranose ring, can be treated as
      spherical in the charge density model which was supported by theoretical
      calculations. Apart from the predominant electrostatic interactions, four
      relatively strong hydrogen bond types further support the stability of the
      crystal structure. This results in a compact and quite uniform structure (in all
      directions) of the studied crystal, as opposed to similar cases with layered
      architecture reported in the literature.

PMID- 28762968
TI  - Insights on spin delocalization and spin polarization mechanisms in crystals of
      azido copper(II) dinuclear complexes through the electron spin density Source
      Function.
AB  - The Source Function (SF) tool was applied to the analysis of the theoretical spin
      density in azido CuII dinuclear complexes, where the azido group, acting as a
      coupler between the CuII cations, is linked to the metal centres either in an end
      on or in an end-end fashion. Results for only the former structural arrangement
      are reported in the present paper. The SF highlights to which extent the magnetic
      centres contribute to determine the local spin delocalization and polarization at
      any point in the dimetallic complex and whether an atom or group of atoms of the
      ligands act in favour or against a given local spin delocalization/polarization.
      Ball-and-stick atomic SF percentage representations allow for a visualization of
      the magnetic pathways and of the specific role played by each atom along these
      paths, at given reference points. Decomposition of SF contributions in terms of a
      magnetic and of a relaxation component provides further insight. Reconstruction
      of partial spin densities by means of the Source Function has for the first time
      been introduced. At variance with the standard SF percentage representations,
      such reconstructions offer a simultaneous view of the sources originating from
      specific subsets of contributing atoms, in a selected molecular plane or in the
      whole space, and are therefore particularly informative. The SF tool is also used
      to evaluate the accuracy of the analysed spin densities. It is found that those
      obtained at the unrestricted B3LYP DFT level, relative to those computed at the
      CASSCF(6,6) level, greatly overestimate spin delocalization to the ligands, but
      comparatively underestimate magnetic connection (spin transmission) among atoms,
      along the magnetic pathways. As a consequence of its excessive spin
      delocalization, the UB3LYP method also overestimates spin polarization mechanisms
      between the paramagnetic centres and the ligands. Spin delocalization measures
      derived from the refinement of Polarized Neutron Diffraction data seem in general
      superior to those obtained through the DFT UB3LYP approach and closer to the far
      more accurate CASSCF results. It is also shown that a visual agreement on the
      spin-resolved electron densities rhoalpha and rhobeta derived from different
      approaches does not warrant a corresponding agreement between their associated
      spin densities.

PMID- 28762969
TI  - Exploring charge density analysis in crystals at high pressure: data collection,
      data analysis and advanced modelling.
AB  - The possibility to determine electron-density distribution in crystals has been
      an enormous breakthrough, stimulated by a favourable combination of equipment for
      X-ray and neutron diffraction at low temperature, by the development of
      simplified, though accurate, electron-density models refined from the
      experimental data and by the progress in charge density analysis often in
      combination with theoretical work. Many years after the first successful charge
      density determination and analysis, scientists face new challenges, for example:
      (i) determination of the finer details of the electron-density distribution in
      the atomic cores, (ii) simultaneous refinement of electron charge and spin
      density or (iii) measuring crystals under perturbation. In this context, the
      possibility of obtaining experimental charge density at high pressure has
      recently been demonstrated [Casati et al. (2016). Nat. Commun. 7, 10901]. This
      paper reports on the necessities and pitfalls of this new challenge, focusing on
      the species syn-1,6:8,13-biscarbonyl[14]annulene. The experimental requirements,
      the expected data quality and data corrections are discussed in detail, including
      warnings about possible shortcomings. At the same time, new modelling techniques
      are proposed, which could enable specific information to be extracted, from the
      limited and less accurate observations, like the degree of localization of double
      bonds, which is fundamental to the scientific case under examination.

PMID- 28762970
TI  - Interplay of point multipole moments and charge penetration for intermolecular
      electrostatic interaction energies from the University at Buffalo pseudoatom
      databank model of electron density.
AB  - The strength of the University at Buffalo DataBank (UBDB) in Ees estimation is
      mainly due to charge overlap effects because the UBDB offers continuous
      representation of charge density which allows for a direct account of charge
      penetration in the derivation of electrostatic energies. In the UBDB model, these
      effects begin to play an important role at distances below twice the equilibrium
      distance and significantly increase as distances decrease. At equilibrium
      distances they are responsible for 30-50% of Ees for polar molecules and around
      90% of Ees for nonpolar molecules. When the energy estimation from the UBDB is
      reduced to point multipoles, the results are comparable to point charges fitted
      to electrostatic potentials. On the other hand, particular components of energy
      from point multipole moments from the UBDB model are sensitive to the type of
      interaction and might be helpful in the characterization of interactions.

PMID- 28762971
TI  - A theoretical-electron-density databank using a model of real and virtual
      spherical atoms.
AB  - A database describing the electron density of common chemical groups using
      combinations of real and virtual spherical atoms is proposed, as an alternative
      to the multipolar atom modelling of the molecular charge density. Theoretical
      structure factors were computed from periodic density functional theory
      calculations on 38 crystal structures of small molecules and the charge density
      was subsequently refined using a density model based on real spherical atoms and
      additional dummy charges on the covalent bonds and on electron lone-pair sites.
      The electron-density parameters of real and dummy atoms present in a similar
      chemical environment were averaged on all the molecules studied to build a
      database of transferable spherical atoms. Compared with the now-popular databases
      of transferable multipolar parameters, the spherical charge modelling needs fewer
      parameters to describe the molecular electron density and can be more easily
      incorporated in molecular modelling software for the computation of electrostatic
      properties. The construction method of the database is described. In order to
      analyse to what extent this modelling method can be used to derive meaningful
      molecular properties, it has been applied to the urea molecule and to
      biotin/streptavidin, a protein/ligand complex.

PMID- 28762972
TI  - Exploring the rare S-H...S hydrogen bond using charge density analysis in isomers
      of mercaptobenzoic acid.
AB  - Experimental and theoretical charge density analyses on isomers of
      mercaptobenzoic acid have been carried out to quantify the hydrogen bonding of
      the hitherto less explored thiols, to assess the strength of the interactions
      using the topological features of the electron density. The electron density
      study offers interesting insights into the nature of the S-H...S interaction. The
      interaction energy is comparable with that of a weak hydrogen bond. The strength
      and directionality of the S-H...S hydrogen bond is demonstrated to be mainly due
      to the conformation locking potential of the intramolecular S...O chalcogen bond
      in 2-mercaptobenzoic acid and is stronger than in 3-mercaptobenzoic acid, which
      lacks the intramolecular S...O bond. The para-substituted mercaptobenzoic acid
      depicts a type I S...S interaction.

PMID- 28762973
TI  - Charge density studies of 3d metal (Ni/Cu) complexes with a non-innocent ligand.
AB  - High-resolution X-ray diffraction experiments and atom-specific X-ray absorption
      experiments are applied to investigate a series of square planar complexes with
      the non-innocent ligand of maleonitriledithiolate (mnt), [S2C2(CN)2]z-,
      containing M-S bonds. Four complexes of (PyH)z[M(mnt)2]z-, where M = Ni or Cu, z
      = 2 or 1 and PyH+ = C5NH6+, were studied in order to clarify whether such one
      electron oxidation-reduction, [M(mnt)2]2-/[M(mnt)2]1-, is taking place at the
      metal or the ligand site. Combining the techniques of metal K-, L-edge and S K
      edge X-ray absorption spectroscopy with high-resolution X-ray charge density
      studies, it is unambiguously demonstrated that the electron redox reaction is
      ligand based and metal based for Ni and Cu pairs, respectively. The bonding
      characters in terms of topological properties associated with the bond critical
      points are compared between the oxidized form [ML]- and the reduced form [ML]2-.
      In the case of Ni complexes, the formal oxidation state of Ni remains as Ni2+ and
      each mnt ligand carries a 2- charge in [Ni(mnt)2]2-, but only one of the ligands
      is formally oxidized in [Ni(mnt)2]1-. In contrast, in the case of Cu complexes,
      the mnt remains as 2- in both complexes, but the formal oxidation states of the
      metal are Cu2+ and Cu3+. Bond characterizations and d-orbital populations will be
      presented. The complementary results of XAS, XRD and DFT calculations will be
      discussed. The conclusion on the redox reactions in these complexes can be firmly
      established.

PMID- 28762974
TI  - Experimental observation of charge-shift bond in fluorite CaF2.
AB  - On the basis of a multipole refinement of single-crystal X-ray diffraction data
      collected using an Ag source at 90 K to a resolution of 1.63 A-1, a quantitative
      experimental charge density distribution has been obtained for fluorite (CaF2).
      The atoms-in-molecules integrated experimental charges for Ca2+ and F- ions are
      +1.40 e and -0.70 e, respectively. The derived electron-density distribution,
      maximum electron-density paths, interaction lines and bond critical points along
      Ca2+...F- and F-...F- contacts revealed the character of these interactions. The
      Ca2+...F- interaction is clearly a closed shell and ionic in character. However,
      the F-...F- interaction has properties associated with the recently recognized
      type of interaction referred to as 'charge-shift' bonding. This conclusion is
      supported by the topology of the electron localization function and analysis of
      the quantum theory of atoms in molecules and crystals topological parameters. The
      Ca2+...F- bonded radii - measured as distances from the centre of the ion to the
      critical point - are 1.21 A for the Ca2+ cation and 1.15 A for the F- anion.
      These values are in a good agreement with the corresponding Shannon ionic radii.
      The F-...F- bond path and bond critical point is also found in the CaF2 crystal
      structure. According to the quantum theory of atoms in molecules and crystals,
      this interaction is attractive in character. This is additionally supported by
      the topology of non-covalent interactions based on the reduced density gradient.

PMID- 28762975
TI  - Revisiting the charge density analysis of 2,5-dichloro-1,4-benzoquinone at 20 K.
AB  - A high-resolution X-ray diffraction measurement of 2,5-dichloro-1,4-benzoquinone
      (DCBQ) at 20 K was carried out. The experimental charge density was modeled using
      the Hansen-Coppens multipolar expansion and the topology of the electron density
      was analyzed in terms of the quantum theory of atoms in molecules (QTAIM). Two
      different multipole models, predominantly differentiated by the treatment of the
      chlorine atom, were obtained. The experimental results have been compared to
      theoretical results in the form of a multipolar refinement against theoretical
      structure factors and through direct topological analysis of the electron density
      obtained from the optimized periodic wavefunction. The similarity of the
      properties of the total electron density in all cases demonstrates the robustness
      of the Hansen-Coppens formalism. All intra- and intermolecular interactions have
      been characterized.

PMID- 28762976
TI  - Formation of local spin-state concentration waves during the relaxation from a
      photoinduced state in a spin-crossover polymer.
AB  - The complex relaxation from the photoinduced high-spin phase (PIHS) to the low
      spin phase of the bimetallic two-dimensional coordination spin-crossover polymer
      [Fe[(Hg(SCN)3)2](4,4'-bipy)2]n is reported. During the thermal relaxation,
      commensurate and incommensurate spin-state concentration waves (SSCWs) form.
      However, contrary to the steps forming at thermal equilibrium, associated with
      long-range SSCW order, the SSCWs forming during the relaxation from the PIHS
      phase correspond to short-range order, revealed by diffuse X-ray scattering. This
      is interpreted as resulting from the competition between the two types of SSCW
      order and another structural symmetry breaking, due to ligand ordering, occurring
      at low temperature and precluding long-range SSCW order.

PMID- 28762977
TI  - Solvent exchange in a metal-organic framework single crystal monitored by dynamic
      in situ X-ray diffraction.
AB  - Understanding the processes by which porous solid-state materials adsorb and
      release guest molecules would represent a significant step towards developing
      rational design principles for functional porous materials. To elucidate the
      process of liquid exchange in these materials, dynamic in situ X-ray diffraction
      techniques have been developed which utilize liquid-phase chemical stimuli. Using
      these time-resolved diffraction techniques, the ethanol solvation process in a
      flexible metal-organic framework [Co(AIP)(bpy)0.5(H2O)].2H2O was examined. The
      measurements provide important insight into the nature of the chemical
      transformation in this system including the presence of a previously unreported
      neat ethanol solvate structure.

PMID- 28762978
TI  - The index of dispersion as a metric of quanta - unravelling the Fano factor.
AB  - In statistics, the index of dispersion (or variance-to-mean ratio) is unity
      (sigma2/<x> = 1) for a Poisson-distributed process with variance sigma2 for a
      variable x that manifests as unit increments. Where x is a measure of some
      phenomenon, the index takes on a value proportional to the quanta that constitute
      the phenomenon. That outcome might thus be anticipated to apply for an enormously
      wide variety of applied measurements of quantum phenomena. However, in a photon
      energy proportional radiation detector, a set of M witnessed Poisson-distributed
      measurements {W1, W2,... WM} scaled so that the ideal expectation value of the
      quantum is unity, is generally observed to give sigma2/<W> < 1 because of
      detector losses as broadly indicated by Fano [Phys. Rev. (1947), 72, 26]. In
      other cases where there is spectral dispersion, sigma2/<W> > 1. Here these
      situations are examined analytically, in Monte Carlo simulations, and
      experimentally. The efforts reveal a powerful metric of quanta broadly associated
      with such measurements, where the extension has been made to polychromatic and
      lossy situations. In doing so, the index of dispersion's variously established
      yet curiously overlooked role as a metric of underlying quanta is indicated. The
      work's X-ray aspects have very diverse utility and have begun to find
      applications in radiography and tomography, where the ability to extract spectral
      information from conventional intensity detectors enables a superior level of
      material and source characterization.

PMID- 28762979
TI  - In-house time-resolved photocrystallography on the millisecond timescale using a
      gated X-ray hybrid pixel area detector.
AB  - With the remarkable progress of accelerator-based X-ray sources in terms of
      intensity and brightness, the investigation of structural dynamics from time
      resolved X-ray diffraction methods is becoming widespread in chemistry,
      biochemistry and materials science applications. Diffraction patterns can now be
      measured down to the femtosecond time-scale using X-ray free electron lasers or
      table-top laser plasma X-ray sources. On the other hand, the recent developments
      in photon counting X-ray area detectors offer new opportunities for time-resolved
      crystallography. Taking advantage of the fast read-out, the internal stacking of
      recorded images, and the gating possibilities (electronic shutter) of the XPAD
      hybrid pixel detector, we implemented a laboratory X-ray diffractometer for time
      resolved single-crystal X-ray diffraction after pulsed laser excitation, combined
      with transient optical absorption measurement. The experimental method and
      instrumental setup are described in detail, and validated using the photoinduced
      nitrosyl linkage isomerism of sodium nitroprusside, Na2[Fe(CN)5NO].2H2O, as proof
      of principle. Light-induced Bragg intensity relative variations
      DeltaI(hkl)/I(hkl) of the order of 1%, due to the photoswitching of the NO
      ligand, could be detected with a 6 ms acquisition window. The capabilities of
      such a laboratory time-resolved experiment are critically evaluated.

PMID- 28762980
TI  - Nanoscale symmetry fluctuations in ferroelectric barium titanate, BaTiO3.
AB  - Crystal charge density is a ground-state electronic property. In ferroelectrics,
      charge is strongly influenced by lattice and vice versa, leading to a range of
      interesting temperature-dependent physical properties. However, experimental
      determination of charge in ferroelectrics is challenging because of the formation
      of ferroelectric domains. Demonstrated here is the scanning convergent-beam
      electron diffraction (SCBED) technique that can be simultaneously used for
      imaging ferroelectric domains and identifying crystal symmetry and its
      fluctuations. Results from SCBED confirm the acentric tetragonal, orthorhombic
      and rhombohedral symmetry for the ferroelectric phases of BaTiO3. However, the
      symmetry is not homogeneous; regions of a few tens of nanometres retaining almost
      perfect symmetry are interspersed in regions of lower symmetry. While the
      observed highest symmetry is consistent with the displacive model of
      ferroelectric phase transitions in BaTiO3, the observed nanoscale symmetry
      fluctuations are consistent with the predictions of the order-disorder phase
      transition mechanism.

PMID- 28762981
TI  - Crystal structure and luminescent properties of novel coordination polymers
      constructed with bifurandicarboxylic acid.
AB  - Four novel coordination polymers (CPs) assembled with [2,2'-bifuran]-5,5'
      dicarboxylic acid (H2L) and metal ions ZnII, CdII or CoII have been successfully
      synthesized. Their molecular structures have been determined to be Zn(L)(H2O)2
      (1), [Zn(L)(DMF)]2 (2), [Cd(L)(EtOH)(DMF)2]2 (3) and Co(L)(H2O)4.(H2O)2 (4) by
      crystallographic analysis. It is found that (2) exhibits a two-dimensional
      infinite framework, whereas the others exhibit a one-dimensional framework. Both
      (2) and (3) exhibit ligand-based emission which is blue-shifted compared with the
      emission from the H2L ligand. Time-resolved spectroscopic measurement reveals
      that the complexes exhibit a similar lifetime with that of the ligand, which
      confirms that the emission of the complexes originates from the ligand.

PMID- 28762982
TI  - Anharmonic motions versus dynamic disorder at the Mg ion from the charge
      densities in pyrope (Mg3Al2Si3O12) crystals at 30 K: six of one, half a dozen of
      the other.
AB  - The possible occurrence of static/dynamic disorder at the Mg site in pyrope
      (Mg3Al2Si3O12), with or without anharmonic contribution to the thermal vibrations
      even at low temperatures, has been largely debated but conclusions were
      contrasting. Here a report is given on the experimental charge density
      distribution, rhoEXP, of synthetic pyrope at T = 30 K, built through a Stewart
      multipolar expansion up to l = 5 and based on a very precise and accurate set of
      in-home measured single-crystal X-ray diffraction amplitudes with a maximum
      resolution of 0.44 A. Local and integral topological properties of rhoEXP are in
      substantial agreement with those of rhoTHEO, the corresponding DFT-grade quantum
      charge density of an ideal pyrope crystal, and those derived from synchrotron
      investigations of chemical bonding in olivines. Relevant thermal atomic
      displacements, probably anharmonic in nature, clearly affect the whole structure
      down to 30 K. No significant (> 2.5sigma) residual Fourier peaks are detectable
      from the rhoEXP distribution around Mg, after least-squares refinement of a
      multipole model with anharmonic thermal motion at the Mg site. Experimental
      findings were confirmed by a full analysis of normal vibration modes of the DFT
      optimized structure of the perfect pyrope crystal. Mg undergoes wide
      displacements from its equilibrium position even at very low temperatures, as it
      is allocated in a ~ 4.5 A large dodecahedral cavity and involved in several soft
      phonon modes. Implications on the interplay among static/dynamic disorder of Mg
      and lattice vibrational degrees of freedom are discussed.

PMID- 28762983
TI  - Synthesis, structure and non-linear optical properties of new isostructural beta
      D-fructopyranose alkaline halide metal-organic frameworks: a theoretical and an
      experimental study.
AB  - In this work four metal-organic framework isomorphs, based on fructose and alkali
      earth halogenides, were investigated to better understand the effect of the size
      of the cation and the different polarizability of the anion on the calculated
      hyperpolarizability and optical susceptibility, which are correlated to non
      linear optical properties. The compounds were characterized by X-ray diffraction
      and the first hyperpolarizability and the second-order susceptibility were
      obtained from theoretical calculations. Furthermore, a new method to measure the
      second-harmonic (SH) efficiency on a small quantity of powder at different
      wavelengths of excitation was optimized and an attempt was made to assess the
      reduction of the SH intensity for small quantities of nano-crystals, in order to
      ascertain the possibility of applications in biological systems. The results of
      this work show that both the intrinsic nature of the anion and the induced
      dissociation of cations and anions by fructose play a role in the second-harmonic
      generating properties of such compounds.

PMID- 28762984
TI  - Local structure and stacking disorder of chloro(phthalocyaninato)aluminium.
AB  - Chloro(phthalocyaninato)aluminium [(C32H16N8)AlCl, Pigment Blue 79] is a
      molecular compound which crystallizes in a layer structure with stacking
      disorder. Order-disorder theory was applied to analyse and explain the stacking
      disorder and to determine the symmetry operations, which generate subsequent
      layers from a given one. Corresponding ordered structural models were constructed
      and optimized by force field and dispersion-corrected density functional theory
      methods. The superposition of the four lowest-energy stackings lead to a
      structure in which every second double layer looks to be ordered; in the other
      double layers the molecules occupy one of two lateral positions. This calculated
      superposition structure agrees excellently with an (incomplete) experimental
      structure determined from single-crystal data. From the optimized ordered models,
      the stacking probabilities and the preferred local arrangements were derived.
      Packing effects such as the distortion of the molecules depending on the
      arrangement of neighbouring molecules could also be determined.

PMID- 28762985
TI  - Validation of missed space-group symmetry in X-ray powder diffraction structures
      with dispersion-corrected density functional theory.
AB  - More than 600 molecular crystal structures with correct, incorrect and uncertain
      space-group symmetry were energy-minimized with dispersion-corrected density
      functional theory (DFT-D, PBE-D3). For the purpose of determining the correct
      space-group symmetry the required tolerance on the atomic coordinates of all non
      H atoms is established to be 0.2 A. For 98.5% of 200 molecular crystal structures
      published with missed symmetry, the correct space group is identified; there are
      no false positives. Very small, very symmetrical molecules can end up in
      artificially high space groups upon energy minimization, although this is easily
      detected through visual inspection. If the space group of a crystal structure
      determined from powder diffraction data is ambiguous, energy minimization with
      DFT-D provides a fast and reliable method to select the correct space group.

PMID- 28762986
TI  - Crystal structures of eta''-Cu3+xSi and eta'''-Cu3+xSi.
AB  - The binary phase diagram of Cu-Si is unexpectedly complex in the vicinity of
      Cu3+xSi. The low-temperature region contains three closely related
      incommensurately modulated phases denoted, in order of increasing temperature of
      stability, eta''', eta'' and eta'. The structure analysis of eta' has been
      reported previously [Palatinus et al. (2011). Inorg. Chem. 50, 3743]. Here the
      structure model for the phases eta'' and eta''' is reported. The structures could
      be solved in superspace, but no superspace structure model could be constructed
      due to the complexity of the modulation functions. Therefore, the structures were
      described in a supercell approximation, which involved a 4 * 4 * 3 supercell for
      the eta'' phase and a 14 * 14 * 3 supercell for the eta''' phase. Both structures
      are very similar and differ only by a subtle symmetry lowering from eta'' to
      eta'''. A comparison of the structure models of eta'' and eta''' with the
      reported structure of eta' suggests that the reported structure model of eta'
      contains an incorrect assignment of atomic types.

PMID- 28762988
TI  - Defining Scholarship in Physician Assistant Education.
AB  - The goal of educational scholarship is to establish evidence that identifies
      excellence in teaching, curriculum design, student assessment, mentoring,
      advising, leadership, and administration. Our challenge as faculty is to
      determine what best defines this within our profession. Responsibilities of
      physician assistant (PA) educators include not only increasing evidence
      supporting quality in PA education but also outlining strategies that lead us to
      this success. As innovative scholars, we should focus on expanding the definition
      of educational scholarship by reevaluating criteria that define it. We then can
      explore new opportunities for faculty to develop a portfolio that endorses their
      academic advancement. The outcomes of this scholarship can be used to further
      advance PA education and clinical practice. Educational scholarship should
      satisfy the following: address a need, expand existing research, and be
      provocative, measurable, and reproducible. As innovative scholars, we should also
      consider analyzing existing evidence and determine whether what has been defined
      as best practices in the general areas of health care education are also
      effective in PA education. The outcomes of this research can be used to establish
      best practices within PA education. Cultivating a collaborative environment among
      programs will enable our profession to gather robust evidence supporting a
      quality education.

PMID- 28762989
TI  - Investigational Overview of Supervised Clinical Practice Experiences.
AB  - PURPOSE: While the Accreditation Review Commission on Education for the Physician
      Assistant (ARC-PA) provides standards, there is variation allowed in design and
      implementation of supervised clinical practice experiences (SCPEs). Limited
      research has assessed for a correlation between SCPE design and program outcomes,
      including PANCE "First-Time Taker Pass Rate." The objective of this research is
      to evaluate for trends and best practices in clinical education design, as well
      as any correlation to PANCE pass rate. METHODS: Data were gathered through an
      online survey with 14 multiple-choice questions referring to "core" clinical
      rotations and then anonymously tabulated. Participants were identified by ARC
      PA's listing of PA programs as of May 2014, excluding those programs with
      "Accreditation-Provisional" or "Accreditation-Probation" statuses. Contact was
      initiated with one faculty member at each program. A post hoc analysis was
      performed to evaluate for correlations between SCPE design and PANCE pass rates.
      RESULTS: Our research quantifies variation in many aspects of the administration
      and design of the clinical education curriculum. During post hoc analysis, the
      groups were divided into "above average" and "average or below" in relation to
      PANCE pass rates compared with the national average, with several significant
      differences identified. These differences include the average length of rotation,
      programs that require a minimum end-of-rotation passing score, and programs that
      require a minimum score on the preceptor evaluation. CONCLUSIONS: This research
      demonstrated many viable options and approaches to various components of clinical
      education, as well as some correlations between supervised clinical practice
      experience (SCPE) design and PANCE first-time taker pass rates.

PMID- 28762990
TI  - Factors that Influence a Physician Assistant/Associate Student Career Choice: An
      Exploratory Study of Students from the United States and United Kingdom.

PMID- 28762992
TI  - Individualized Patient-Centered Care: A Physician Assistant Curriculum in
      Information Mastery, Clinical Reasoning, and Shared Decision Making.

PMID- 28762991
TI  - Evaluating Motivational Interviewing in the Physician Assistant Curriculum.
AB  - PURPOSE: Motivational interviewing (MI) is an evidence-based technique that
      enables clinicians to help patients modify health behaviors. Although MI is an
      essential tool for physician assistants (PAs), the extent to which it is
      addressed in PA curricula in the United States is unknown. This study is a
      comprehensive description of MI education in PA programs in the United States.
      METHODS: Data are from the 2014 Physician Assistant Education Association Annual
      Program Survey. Descriptive statistics were conducted on de-identified data from
      all 186 PA programs in the United States. RESULTS: Of the 186 PA programs
      surveyed, 72.58% (n = 135) reported at least one course providing MI training.
      Availability of courses providing training in skills essential to the MI process
      varied. Having a course with verbal communication training was most frequently
      endorsed, and having a course with training in developing discrepancy was least
      frequently endorsed. The most popular teaching modality was lecture (84.95%, n =
      158), whereas only 41.40% (n = 77) and 58.60% (n = 109) reported role play with
      evaluation and standardized patient exercises with evaluation, respectively.
      CONCLUSIONS: More than 70% of programs included at least one course in their
      curriculum that provided training in MI, suggesting that PA programs recognize
      the importance of MI. Instruction in change talk was not provided in nearly half
      of the programs. Role-play and standardized patient exercises with evaluation
      were underused methods despite their proven efficacy in MI education. As the
      first comprehensive benchmark of MI education for PAs, this study shows that
      although most programs address MI, opportunities exist to improve MI training in
      PA programs in the United States.

PMID- 28762993
TI  - Should Lifestyle Medicine Be a Core Curricular Component for Physician Assistant
      Students?

PMID- 28762987
TI  - Autoreactive T cells in type 1 diabetes.
AB  - Type 1 diabetes (T1D) is a chronic autoimmune disease that causes severe loss of
      pancreatic beta cells. Autoreactive T cells are key mediators of beta cell
      destruction. Studies of organ donors with T1D that have examined T cells in
      pancreas, the diabetogenic insulitis lesion, and lymphoid tissues have revealed a
      broad repertoire of target antigens and T cell receptor (TCR) usage, with initial
      evidence of public TCR sequences that are shared by individuals with T1D.
      Neoepitopes derived from post-translational modifications of native antigens are
      emerging as novel targets that are more likely to evade self-tolerance. Further
      studies will determine whether T cell responses to neoepitopes are major disease
      drivers that could impact prediction, prevention, and therapy. This Review
      provides an overview of recent progress in our knowledge of autoreactive T cells
      that has emerged from experimental and clinical research as well as pathology
      investigations.

PMID- 28762994
TI  - Tomorrow You Will Be Allowed to... Diagnose the Patient!

PMID- 28762995
TI  - Using Mobile Apps in Physician Assistant Education.

PMID- 28762996
TI  - The Americans With Disabilities Act and Test Anxiety: When Accommodations Are
      Appropriate.

PMID- 28762998
TI  - Highly Sensitive Hot-Wire Anemometry Based on Macro-Sized Double-Walled Carbon
      Nanotube Strands.
AB  - This paper presents a highly sensitive flow-rate sensor with carbon nanotubes
      (CNTs) as sensing elements. The sensor uses micro-size centimeters long double
      walled CNT (DWCNT) strands as hot-wires to sense fluid velocity. In the
      theoretical analysis, the sensitivity of the sensor is demonstrated to be
      positively related to the ratio of its surface. We assemble the flow sensor by
      suspending the DWCNT strand directly on two tungsten prongs and dripping a small
      amount of silver glue onto each contact between the DWCNT and the prongs. The
      DWCNT exhibits a positive TCR of 1980 ppm/K. The self-heating effect on the DWCNT
      was observed while constant current was applied between the two prongs. This
      sensor can evidently respond to flow rate, and requires only several milliwatts
      to operate. We have, thus far, demonstrated that the CNT-based flow sensor has
      better sensitivity than the Pt-coated DWCNT sensor.

PMID- 28762997
TI  - Investigating the Biosynthesis of Natural Products from Marine Proteobacteria: A
      Survey of Molecules and Strategies.
AB  - The phylum proteobacteria contains a wide array of Gram-negative marine bacteria.
      With recent advances in genomic sequencing, genome analysis, and analytical
      chemistry techniques, a whole host of information is being revealed about the
      primary and secondary metabolism of marine proteobacteria. This has led to the
      discovery of a growing number of medically relevant natural products, including
      novel leads for the treatment of multidrug-resistant Staphylococcus aureus (MRSA)
      and cancer. Of equal interest, marine proteobacteria produce natural products
      whose structure and biosynthetic mechanisms differ from those of their
      terrestrial and actinobacterial counterparts. Notable features of secondary
      metabolites produced by marine proteobacteria include halogenation, sulfur
      containing heterocycles, non-ribosomal peptides, and polyketides with unusual
      biosynthetic logic. As advances are made in the technology associated with
      functional genomics, such as computational sequence analysis, targeted DNA
      manipulation, and heterologous expression, it has become easier to probe the
      mechanisms for natural product biosynthesis. This review will focus on genomics
      driven approaches to understanding the biosynthetic mechanisms for natural
      products produced by marine proteobacteria.

PMID- 28762999
TI  - Immunological Responses to Total Hip Arthroplasty.
AB  - The use of total hip arthroplasties (THA) has been continuously rising to meet
      the demands of the increasingly ageing population. To date, this procedure has
      been highly successful in relieving pain and restoring the functionality of
      patients' joints, and has significantly improved their quality of life. However,
      these implants are expected to eventually fail after 15-25 years in situ due to
      slow progressive inflammatory responses at the bone-implant interface. Such
      inflammatory responses are primarily mediated by immune cells such as
      macrophages, triggered by implant wear particles. As a result, aseptic loosening
      is the main cause for revision surgery over the mid and long-term and is
      responsible for more than 70% of hip revisions. In some patients with a metal-on
      metal (MoM) implant, metallic implant wear particles can give rise to metal
      sensitivity. Therefore, engineering biomaterials, which are immunologically inert
      or support the healing process, require an in-depth understanding of the host
      inflammatory and wound-healing response to implanted materials. This review
      discusses the immunological response initiated by biomaterials extensively used
      in THA, ultra-high-molecular-weight polyethylene (UHMWPE), cobalt chromium
      (CoCr), and alumina ceramics. The biological responses of these biomaterials in
      bulk and particulate forms are also discussed. In conclusion, the immunological
      responses to bulk and particulate biomaterials vary greatly depending on the
      implant material types, the size of particulate and its volume, and where the
      response to bulk forms of differing biomaterials are relatively acute and
      similar, while wear particles can initiate a variety of responses such as
      osteolysis, metal sensitivity, and so on.

PMID- 28763000
TI  - Conditioned Medium from Malignant Breast Cancer Cells Induces an EMT-Like
      Phenotype and an Altered N-Glycan Profile in Normal Epithelial MCF10A Cells.
AB  - Epithelial-mesenchymal transition (EMT) is a key process in cancer development
      and progression. Communication (crosstalk) between cancer cells and normal
      (nonmalignant) cells may facilitate cancer progression. Conditioned medium (CM)
      obtained from cultured cancer cells contains secreted factors capable of
      affecting phenotypes and the behaviors of normal cells. In this study, a culture
      of normal breast epithelial MCF10A cells with CM from malignant breast cancer
      cells (termed 231-CM and 453-CM) resulted in an alteration of morphology. CM
      treated MCF10A, in comparison with control cells, showed a reduced expression of
      the epithelial marker E-cadherin, increased expression of the mesenchymal markers
      fibronectin, vimentin, N-cadherin, and TWIST1, meanwhile cell proliferation and
      migration were enhanced while cell apoptosis was decreased. N-glycan profiles of
      231-CM-treated and control MCF10A cells were compared by MALDI-TOF/TOF-MS (Matrix
      Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry) and a
      lectin microarray analysis. The treated cells showed lower levels of high-mannose
      type N-glycan structures, and higher levels of complex-type and hybrid-type
      structures. Altered N-glycan profiles were also detected in 453-CM-treated and
      non-treated MCF10A cells by MALDI-TOF/TOF-MS, and we found that the expression of
      five fucosylated N-glycan structures (m/z 1406.663, 1590.471, 1668.782, 2421.141,
      and 2988.342) and one high-mannose structure m/z 1743.722 have the same pattern
      as 231-CM-treated MCF10A cells. Our findings, taken together, show that CM
      derived from breast cancer cells induced an EMT-like process in normal epithelial
      cells and altered their N-glycan profile.

PMID- 28763001
TI  - Functional and Promoter Analysis of ChiIV3, a Chitinase of Pepper Plant, in
      Response to Phytophthora capsici Infection.
AB  - Despite the involvement of many members of the chitinase family in plant
      immunity, the precise functions of the majority of the members remain poorly
      understood. Herein, the gene ChiIV3 in Capsicum annuum encoding a chitinase
      protein containing a chitin binding domain and targeting to the plasma membrane
      was found to be induced by Phytophthora capsici inoculation (PCI) and applied
      chitin treatment. Besides its direct inhibitory effect on growth of Phytophthora
      capsici (P. capsici), ChiIV3 was also found by virus-induced gene silencing
      (VIGS) and transient overexpression (TOE) in pepper plants to act as a positive
      regulator of plant cell death and in triggering defense signaling and
      upregulation of PR (pathogenesis related) genes against PCI. A 5' deletion assay
      revealed that pChiIV3-712 to -459 bp was found to be sufficient for ChiIV3'
      response to PCI. Furthermore, a mutation assay indicated that W-box-466 to -461
      bp in pChiIV3-712 to -459 bp was noted to be the PCI-responsible element. These
      results collectively suggest that ChiIV3 acts as a likely antifungal protein and
      as a receptor for unidentified chitin in planta to trigger cell death and defense
      signaling against PCI.

PMID- 28763002
TI  - Toll-Like Receptor-4 Inhibitor TAK-242 Attenuates Motor Dysfunction and Spinal
      Cord Pathology in an Amyotrophic Lateral Sclerosis Mouse Model.
AB  - Neuroinflammation contributes to amyotrophic lateral sclerosis (ALS) progression.
      TLR4, a transmembrane protein that plays a central role in activation of the
      innate immune system, has been shown to induce microglial activation in ALS
      models. TLR4 is up-regulated in the spinal cords of hSOD1G93A mice. We aimed to
      examine the effects of specific TLR4 inhibition on disease progression and
      survival in the hSOD1G93A mouse model of ALS. Immunologic effect of TLR4
      inhibition in vitro was measured by the effect of TAK-242 treatment on LPS
      induced splenocytes proliferation. hSOD1G93A transgenic mice were treated with
      TAK-242, a selective TLR4 inhibitor, or vehicle. Survival, body weight, and motor
      behavior were monitored. To evaluate in vivo immunologic modifications associated
      with TAK-242 treatment, we measured serum IL-1beta in the plasma, as well as IL
      1beta and TNF-alpha mRNAs in the spinal cord in wild-type mice and in TAK-242
      treated and vehicle-treated early symptomatic hSOD1G93A mice. Immunohistochemical
      analysis of motor neurons, astrocytes, and microglial reactivity in the spinal
      cords were performed on symptomatic (100 days old) TAK-242-treated and vehicle
      treated hSOD1G93A mice. In vitro, splenocytes taken from 100 days old hSOD1G93A
      mice showed significantly increased proliferation when exposed to LPS (p =
      0.0002), a phenomenon that was reduced by TAK-242 (p = 0.0179). TAK-242 treatment
      did not attenuate body weight loss or significantly affect survival. However, TAK
      242-treated hSOD1G93A mice showed temporary clinical delay in disease progression
      evident in the ladder test and hindlimb reflex measurements. Plasma IL-1beta
      levels were significantly reduced in TAK-242-treated compared to vehicle-treated
      hSOD1G93A mice (p = 0.0023). TAK-242 treatment reduced spinal cord astrogliosis
      and microglial activation and significantly attenuated spinal cord motor neuron
      loss at early disease stage (p = 0.0259). Compared to wild-type animals, both IL
      1beta and TNF-alpha mRNAs were significantly upregulated in the spinal cords of
      hSOD1G93A mice. Spinal cord analysis in TAK-242-treated hSOD1G93A mice revealed
      significant attenuation of TNF-alpha mRNA (p = 0.0431), but no change in IL-1beta
      mRNA. TLR4 inhibition delayed disease progression, attenuated spinal cord
      astroglial and microglial reaction, and reduced spinal motor neuron loss in the
      ALS hSOD1G93A mouse model. However, this effect did not result in increased
      survival. To our knowledge, this is the first report on TAK-242 treatment in a
      neurodegenerative disease model. Further studies are warranted to assess TLR4 as
      a therapeutic target in ALS.

PMID- 28763003
TI  - Short-Term Effects of a Ready-to-Drink Pre-Workout Beverage on Exercise
      Performance and Recovery.
AB  - In a double-blind, randomized and crossover manner, 25 resistance-trained
      participants ingested a placebo (PLA) beverage containing 12 g of dextrose and a
      beverage (RTD) containing caffeine (200 mg), beta-alanine (2.1 g), arginine
      nitrate (1.3 g), niacin (65 mg), folic acid (325 mcg), and Vitamin B12 (45 mcg)
      for 7-days, separated by a 7-10-day. On day 1 and 6, participants donated a
      fasting blood sample and completed a side-effects questionnaire (SEQ),
      hemodynamic challenge test, 1-RM and muscular endurance tests (3 * 10 repetitions
      at 70% of 1-RM with the last set to failure on the bench press (BP) and leg press
      (LP)) followed by ingesting the assigned beverage. After 15 min, participants
      repeated the hemodynamic test, 1-RM tests, and performed a repetition to fatigue
      (RtF) test at 70% of 1-RM, followed by completing the SEQ. On day 2 and 7,
      participants donated a fasting blood sample, completed the SEQ, ingested the
      assigned beverage, rested 30 min, and performed a 4 km cycling time-trial (TT).
      Data were analyzed by univariate, multivariate, and repeated measures general
      linear models (GLM), adjusted for gender and relative caffeine intake. Data are
      presented as mean change (95% CI). An overall multivariate time * treatment
      interaction was observed on strength performance variables (p = 0.01). Acute RTD
      ingestion better maintained LP 1-RM (PLA: -0.285 (-0.49, -0.08); RTD: 0.23 (
      0.50, 0.18) kg/kgFFM, p = 0.30); increased LP RtF (PLA: -2.60 (-6.8, 1.6); RTD:
      4.00 (-0.2, 8.2) repetitions, p = 0.031); increased BP lifting volume (PLA: 0.001
      (-0.13, 0.16); RTD: 0.03 (0.02, 0.04) kg/kgFFM, p = 0.007); and, increased total
      lifting volume (PLA: -13.12 (-36.9, 10.5); RTD: 21.06 (-2.7, 44.8) kg/kgFFM, p =
      0.046). Short-term RTD ingestion maintained baseline LP 1-RM (PLA: -0.412 (-0.08,
      -0.07); RTD: 0.16 (-0.50, 0.18) kg/kgFFM, p = 0.30); LP RtF (PLA: 0.12 (-3.0,
      3.2); RTD: 3.6 (0.5, 6.7) repetitions, p = 0.116); and, LP lifting volume (PLA:
      3.64 (-8.8, 16.1); RTD: 16.25 (3.8, 28.7) kg/kgFFM, p = 0.157) to a greater
      degree than PLA. No significant differences were observed between treatments in
      cycling TT performance, hemodynamic assessment, fasting blood panels, or self
      reported side effects.

PMID- 28763004
TI  - The Linoleic Acid: Dihomo-gamma-Linolenic Acid Ratio (LA:DGLA)-An Emerging
      Biomarker of Zn Status.
AB  - Zinc (Zn) deficiency is a common aliment predicted to affect 17% of the world's
      population. Zinc is a vital micronutrient used for over 300 enzymatic reactions
      and multiple biochemical and structural processes in the body. Although whole
      blood, plasma, and urine zinc decrease in severe zinc deficiency, accurate
      assessment of zinc status, especially in mild to moderate deficiency, is
      difficult as studies with these biomarkers are often contradictory and
      inconsistent. Hence, as suggested by the World Health Organization, sensitive and
      specific biological markers of zinc status are still needed. In this review, we
      provide evidence to demonstrate that the LA:DGLA ratio (linoleic acid:dihomo
      gamma-linolenic acid ratio) may be a useful additional indicator for assessing Zn
      status more precisely. However, this biomarker needs to be tested further in
      order to determine its full potential.

PMID- 28763005
TI  - Seasonal Variation in Fat Quality and Conjugated Linoleic Acid Content of Dairy
      Products from the Tropics: Evidence of Potential Impact on Human Health.
AB  - Seasonal variation in conjugated linoleic acid (CLA) content and atherogenicity
      index (AI) of retail dairy products (whole milk, butter, and prato, a soft yellow
      cheese) from Brazil was investigated. CLA content of dairy products ranged from
      0.55 to 1.53 g CLA/100 g fatty acids and was on average 25% higher during the
      rainy season compared to the dry season. Dairy products from the rainy season
      also had lower AI levels, indicating a lower risk of causing cardiovascular
      disease in consumers. This seasonality led to estimated seasonal variations of
      milk fat quality consumed by the population of southeastern Brazil, meaning 15%
      and 19% variation in daily intake of CLA and AI values, respectively. Dietary
      consumption of CLA (g/day) was greater in the rainy season, despite higher intake
      of dairy products during the dry season. We show that dairy products produced
      during the rainy season in Brazil are expected to be more beneficial to human
      health than are those produced during the dry season.

PMID- 28763007
TI  - Variation within Variation: Comparison of 24-h Rhythm in Rodent Infarct Size
      between Ischemia Reperfusion and Permanent Ligation.
AB  - The detrimental effects of myocardial infarction in humans and rodents have a 24
      h rhythm. In some human cohorts however, rhythmicity was absent, while the time
      of maximum damage differs between cohorts. We hypothesized that the type of
      damage influences the 24-h rhythm in infarct size. Myocardial infarction was
      induced in 12-week-old C57BL/six mice at four different time-points during the
      day using either permanent ligation (PL) or 30-min of ischemia followed by
      reperfusion (IR), with a control group wherein no ligation was applied. Infarct
      size was measured by echocardiography and histology at a 1-month follow-up.
      Rhythmicity in infarct size was present in the PL group at the functional and
      histological level, with maximal damage occurring when the infarct was induced at
      noon. In the IR group, no circadian rhythm was found. The time of the coronary
      artery ligation determines the outcome of myocardial infarction. Our data showed
      that in rodents, the presence of circadian rhythmicity and time of peak infarct
      size varies between experimental setups.

PMID- 28763006
TI  - Proteins Recognizing DNA: Structural Uniqueness and Versatility of DNA-Binding
      Domains in Stem Cell Transcription Factors.
AB  - Proteins in the form of transcription factors (TFs) bind to specific DNA sites
      that regulate cell growth, differentiation, and cell development. The
      interactions between proteins and DNA are important toward maintaining and
      expressing genetic information. Without knowing TFs structures and DNA-binding
      properties, it is difficult to completely understand the mechanisms by which
      genetic information is transferred between DNA and proteins. The increasing
      availability of structural data on protein-DNA complexes and recognition
      mechanisms provides deeper insights into the nature of protein-DNA interactions
      and therefore, allows their manipulation. TFs utilize different mechanisms to
      recognize their cognate DNA (direct and indirect readouts). In this review, we
      focus on these recognition mechanisms as well as on the analysis of the DNA
      binding domains of stem cell TFs, discussing the relative role of various amino
      acids toward facilitating such interactions. Unveiling such mechanisms will
      improve our understanding of the molecular pathways through which TFs are
      involved in repressing and activating gene expression.

PMID- 28763008
TI  - Omega-3 Fatty Acids Supplementation Differentially Modulates the SDF-1/CXCR-4
      Cell Homing Axis in Hypertensive and Normotensive Rats.
AB  - BACKGROUND: We assessed the effect of acute and chronic dietary supplementation
      of omega-3 on lipid metabolism and cardiac regeneration, through its influence on
      the Stromal Derived Factor-1 (SDF-1) and its receptor (CXCR4) axis in
      normotensive and hypertensive rats. METHODS: Male Wistar Kyoto (WKY) and
      spontaneously hypertensive rats (SHR) were allocated in eight groups (of eight
      animals each), which received daily orogastric administration of omega-3 (1 g)
      for 24 h, 72 h or 2 weeks. Blood samples were collected for the analysis of the
      lipid profile and SDF-1 systemic levels (ELISA). At the end of the treatment
      period, cardiac tissue was collected for CXCR4 expression analysis (Western
      blot). RESULTS: The use of omega-3 caused a reduction in total cholesterol levels
      (p = 0.044), and acutely activated the SDF-1/CXCR4 axis in normotensive animals
      (p = 0.037). In the presence of the omega-3, after 72 h, SDF-1 levels decreased
      in WKY and increased in SHR (p = 0.017), and tissue expression of the receptor
      CXCR4 was higher in WKY than in SHR (p = 0.001). CONCLUSION: The omega-3 fatty
      acid supplementation differentially modulates cell homing mediators in
      normotensive and hypertensive animals. While WKY rats respond acutely to omega-3
      supplementation, showing increased release of SDF-1 and CXCR4, SHR exhibit a
      weaker, delayed response.

PMID- 28763009
TI  - Metal Binding Properties of the N-Terminus of the Functional Amyloid Orb2.
AB  - The cytoplasmic polyadenylation element binding protein (CPEB) homologue Orb2 is
      a functional amyloid that plays a key regulatory role for long-term memory in
      Drosophila. Orb2 has a glutamine, histidine-rich (Q/H-rich) domain that resembles
      the Q/H-rich, metal binding domain of the Hpn-like protein (Hpnl) found in
      Helicobacter pylori. In the present study, we used chromatography and isothermal
      titration calorimetry (ITC) to show that the Q/H-rich domain of Orb2 binds Ni2+
      and other transition metals ions with MUM affinity. Using site directed
      mutagenesis, we show that several histidine residues are important for binding.
      In particular, the H61Y mutation, which was previously shown to affect the
      aggregation of Orb2 in cell culture, completely inhibited metal binding of Orb2.
      Finally, we used thioflavin T fluorescence and electron microscopy images to show
      that Ni2+ binding induces the aggregating of Orb2 into structures that are
      distinct from the amyloid fibrils formed in the absence of Ni2+. These data
      suggest that transition metal binding might be important for the function of Orb2
      and potentially long-term memory in Drosophila.

PMID- 28763010
TI  - Chronic Respiratory Disorders and Their Treatment among Older People with
      Intellectual Disability and/or Autism Spectrum Disorder in Comparison with the
      General Population.
AB  - Respiratory disorders are common among people with intellectual disabilities
      (ID). However, few studies have investigated these disorders among older people
      with ID. We identified 7936 people, aged 55+ years, with ID and a reference
      cohort from the general population. Data on diagnoses of chronic respiratory
      disorders, with a focus on asthma and chronic obstructive pulmonary disease
      (COPD), were collected, as was information on health care visits due to such
      disorders. We also added data on the prescription of drugs for obstructive airway
      diseases. Whereas the risk of having at least one diagnosis of asthma during the
      study period was similar in the two cohorts, people with ID were less likely than
      the general population to have been diagnosed with COPD. The same was found for
      health care visits due to asthma and COPD, respectively. The patterns of drug
      prescription were similar among people with ID and the general population, with
      the exception of adrenergics for systemic use, which were more commonly
      prescribed to people with ID. Thus, older people with ID do not seem to have an
      increased risk of asthma or COPD. Moreover, the indications are that when
      diagnosed with any of these disorders, they receive treatment adapted to their
      particular needs.

PMID- 28763011
TI  - An Adaptive Impedance Matching Network with Closed Loop Control Algorithm for
      Inductive Wireless Power Transfer.
AB  - For an inductive wireless power transfer (IWPT) system, maintaining a reasonable
      power transfer efficiency and a stable output power are two most challenging
      design issues, especially when coil distance varies. To solve these issues, this
      paper presents a novel adaptive impedance matching network (IMN) for IWPT system.
      In our adaptive IMN IWPT system, the IMN is automatically reconfigured to keep
      matching with the coils and to adjust the output power adapting to coil distance
      variation. A closed loop control algorithm is used to change the capacitors
      continually, which can compensate mismatches and adjust output power
      simultaneously. The proposed adaptive IMN IWPT system is working at 125 kHz for 2
      W power delivered to load. Comparing with the series resonant IWPT system and
      fixed IMN IWPT system, the power transfer efficiency of our system increases up
      to 31.79% and 60% when the coupling coefficient varies in a large range from 0.05
      to 0.8 for 2 W output power.

PMID- 28763013
TI  - Context- and Template-Based Compression for Efficient Management of Data Models
      in Resource-Constrained Systems.
AB  - The Cyber Physical Systems (CPS) paradigm is based on the deployment of
      interconnected heterogeneous devices and systems, so interoperability is at the
      heart of any CPS architecture design. In this sense, the adoption of standard and
      generic data formats for data representation and communication, e.g., XML or
      JSON, effectively addresses the interoperability problem among heterogeneous
      systems. Nevertheless, the verbosity of those standard data formats usually
      demands system resources that might suppose an overload for the resource
      constrained devices that are typically deployed in CPS. In this work we present
      Context- and Template-based Compression (CTC), a data compression approach
      targeted to resource-constrained devices, which allows reducing the resources
      needed to transmit, store and process data models. Additionally, we provide a
      benchmark evaluation and comparison with current implementations of the Efficient
      XML Interchange (EXI) processor, which is promoted by the World Wide Web
      Consortium (W3C), and it is the most prominent XML compression mechanism
      nowadays. Interestingly, the results from the evaluation show that CTC
      outperforms EXI implementations in terms of memory usage and speed, keeping
      similar compression rates. As a conclusion, CTC is shown to be a good candidate
      for managing standard data model representation formats in CPS composed of
      resource-constrained devices.

PMID- 28763012
TI  - Performance of a RT-PCR Assay in Comparison to FISH and Immunohistochemistry for
      the Detection of ALK in Non-Small Cell Lung Cancer.
AB  - Patients with lung cancers harboring an activating anaplastic lymphoma kinase
      (ALK) rearrangement respond favorably to ALK inhibitor therapy. Fluorescence in
      situ hybridization (FISH) and immunohistochemistry (IHC) are validated and widely
      used screening tests for ALK rearrangements but both methods have limitations.
      The ALK RGQ RT-PCR Kit (RT-PCR) is a single tube quantitative real-time PCR assay
      for high throughput and automated interpretation of ALK expression. In this
      study, we performed a direct comparison of formalin-fixed paraffin-embedded
      (FFPE) lung cancer specimens using all three ALK detection methods. The RT-PCR
      test (diagnostic cut-off DeltaCt of <=8) was shown to be highly sensitive (100%)
      when compared to FISH and IHC. Sequencing of RNA detected full-length ALK
      transcripts or EML4-ALK and KIF5B-ALK fusion variants in discordant cases in
      which ALK expression was detected by the ALK RT-PCR test but negative by FISH and
      IHC. The overall specificity of the RT-PCR test for the detection of ALK in cases
      without full-length ALK expression was 94% in comparison to FISH and sequencing.
      These data support the ALK RT-PCR test as a highly efficient and reliable
      diagnostic screening approach to identify patients with non-small cell lung
      cancer whose tumors are driven by oncogenic ALK.

PMID- 28763014
TI  - Two Hop Adaptive Vector Based Quality Forwarding for Void Hole Avoidance in
      Underwater WSNs.
AB  - Underwater wireless sensor networks (UWSNs) facilitate a wide range of aquatic
      applications in various domains. However, the harsh underwater environment poses
      challenges like low bandwidth, long propagation delay, high bit error rate, high
      deployment cost, irregular topological structure, etc. Node mobility and the
      uneven distribution of sensor nodes create void holes in UWSNs. Void hole
      creation has become a critical issue in UWSNs, as it severely affects the network
      performance. Avoiding void hole creation benefits better coverage over an area,
      less energy consumption in the network and high throughput. For this purpose,
      minimization of void hole probability particularly in local sparse regions is
      focused on in this paper. The two-hop adaptive hop by hop vector-based forwarding
      (2hop-AHH-VBF) protocol aims to avoid the void hole with the help of two-hop
      neighbor node information. The other protocol, quality forwarding adaptive hop by
      hop vector-based forwarding (QF-AHH-VBF), selects an optimal forwarder based on
      the composite priority function. QF-AHH-VBF improves network good-put because of
      optimal forwarder selection. QF-AHH-VBF aims to reduce void hole probability by
      optimally selecting next hop forwarders. To attain better network performance,
      mathematical problem formulation based on linear programming is performed.
      Simulation results show that by opting these mechanisms, significant reduction in
      end-to-end delay and better throughput are achieved in the network.

PMID- 28763015
TI  - Effect of Non-Dairy Food Matrices on the Survival of Probiotic Bacteria during
      Storage.
AB  - The viability of probiotics in non-dairy food products during storage is required
      to meet content criteria for probiotic products. This study investigated whether
      non-dairy foods could be matrices for probiotics. Selected probiotic bacteria
      were coated on non-dairy foods under two storage conditions, and viabilities were
      assessed. The non-dairy foods were coated with 5-7 log cfu g-1 of Lactobacillus
      acidophilus ATCC4356T, Lactobacillus plantarum RC30, and Bifidobacterium longum
      ATCC15707T. The coated non-dairy foods were stored at 20  degrees C and 20%
      relative humidity (RH) or 30  degrees C and 50% RH. Viability of probiotic
      bacteria was determined after 0, 2, and 4 weeks of storage. B. longum showed the
      highest survival at week 4 of 6.5-6.7 log cfu g-1 on wheat bran and oat, compared
      with 3.7-3.9 log cfu g-1 of L. acidophilus and 4.2-4.8 log cfu g-1 of L.
      plantarum at 20  degrees C 20% RH. Under the storage conditions of 30  degrees C
      50% RH, survival of 4.5 log cfu g-1 of B. longum was also found on oat and
      peanut. This was two and four times higher than the population of L. acidophilus
      and L. plantarum, respectively. The results suggest that probiotics can survive
      on non-dairy foods under ambient storage conditions. However, the storage
      conditions, food matrices, and probiotic strains should be carefully chosen to
      maximize probiotic bacteria survival.

PMID- 28763016
TI  - A Multiplex RT-PCR Assay to Detect and Discriminate Porcine Reproductive and
      Respiratory Syndrome Viruses in Clinical Specimens.
AB  - Outbreaks of highly pathogenic porcine reproductive and respiratory syndrome
      virus (HP-PRRSV) have led to large economic losses in China. The attenuated
      vaccine (HP-PRRSV JXA1-R) was used to control HP-PRRSV. However, in recent years,
      co-infection with classical PRRSV (C-PRRSV), HP-PRRSV, and/or HP-PRRSV JXA1-R has
      been increasing in China, resulting in a significant impact on PRRSV diagnostics
      and management. To facilitate rapid discrimination of HP-PRRSV JXA1-R from HP
      PRRSV and C-PRRSV, a multiplex RT-PCR assay for the visual detection of HP-PRRSV
      JXA1-R, HP-PRRSV, and C-PRRSV was established and evaluated with reference PRRSV
      strains and clinical samples. Primer specificities were evaluated with RNA/DNA
      extracted from 10 viral strains, and our results revealed that the primers had a
      high specificity for PRRSV. The assay sensitivity was 24 copies/MUL for PRRSVs. A
      total of 516 serum samples were identified, of which 12.21% (63/516) were HP
      PRRSV-positive, 2.33% (12/516) were HP-PRRSV JXA1-R-positive, and 1.16% (6/516)
      were C-PRRSV-positive, respectively, which was completely consistent with the
      sequencing method. The high specificity, sensitivity, and reliability of the
      multiplex RT-PCR assay described in this study indicate that it is useful for the
      rapid and differential diagnosis of HP-PRRSV JXA1-R, HP-PRRSV, and C-PRRSV.

PMID- 28763017
TI  - Positive and Negative Affect More Concurrent among Blacks than Whites.
AB  - BACKGROUND: While positive and negative affect are inversely linked, people may
      experience and report both positive and negative emotions simultaneously.
      However, it is unknown if race alters the magnitude of the association between
      positive and negative affect. The current study compared Black and White
      Americans for the association between positive and negative affect. METHODS: We
      used data from MIDUS (Midlife in the United States), a national study of
      Americans with an age range of 25 to 75. A total number of 7108 individuals were
      followed for 10 years from 1995 to 2004. Positive and negative affect was
      measured at baseline (1995) and follow-up (2004). Demographic (age and gender),
      socioeconomic (education and income) as well as health (self-rated health,
      chronic medical conditions, and body mass index) factors measured at baseline
      were covariates. A series of linear regressions were used to test the moderating
      effect of race on the reciprocal association between positive and negative affect
      at baseline and over time, net of covariates. RESULTS: In the pooled sample,
      positive and negative affect showed inverse correlation at baseline and over
      time, net of covariates. Blacks and Whites differed in the magnitude of the
      association between positive and negative affect, with weaker inverse
      associations among Blacks compared to Whites, beyond all covariates. CONCLUSION:
      Weaker reciprocal association between positive and negative affect in Blacks
      compared to Whites has implications for cross-racial measurement of affect and
      mood, including depression. Depression screening programs should be aware that
      race alters the concordance between positive and negative affect domains and that
      Blacks endorse higher levels of positive affect compared to Whites in the
      presence of high negative affect.

PMID- 28763019
TI  - Use of Antibiotics for Maintenance of Axenic Cultures of Amphidinium carterae for
      the Analysis of Translation.
AB  - Most dinoflagellates in culture are bacterized, complicating the quantification
      of protein synthesis, as well as the analysis of its regulation. In bacterized
      cultures of Amphidinium carterae Hulbert, up to 80% of protein synthetic activity
      appears to be predominantly bacterial based on responses to inhibitors of protein
      synthesis. To circumvent this, axenic cultures of A. carterae were obtained and
      shown to respond to inhibitors of protein synthesis in a manner characteristic of
      eukaryotes. However, these responses changed with time in culture correlating
      with the reappearance of bacteria. Here we show that culture with kanamycin (50
      MUg/mL), carbenicillin (100 MUg/mL), and streptomycin sulfate (50 MUg/mL) (KCS),
      but not 100 units/mL of penicillin and streptomycin (PS), prevents the
      reappearance of bacteria and allows A. carterae protein synthesis to be
      quantified without the contribution of an associated bacterial community. We
      demonstrate that A. carterae can grow in the absence of a bacterial community.
      Furthermore, maintenance in KCS does not inhibit the growth of A. carterae
      cultures but slightly extends the growth phase and allows accumulation to
      somewhat higher saturation densities. We also show that cultures of A. carterae
      maintained in KCS respond to the eukaryotic protein synthesis inhibitors
      cycloheximide, emetine, and harringtonine. Establishment of these culture
      conditions will facilitate our ability to use polysome fractionation and ribosome
      profiling to study mRNA recruitment. Furthermore, this study shows that a simple
      and fast appraisal of the presence of a bacterial community in A. carterae
      cultures can be made by comparing responses to cycloheximide and chloramphenicol
      rather than depending on lengthier culture-based assessments.

PMID- 28763018
TI  - Maternal Immunization: New Perspectives on Its Application Against Non-Infectious
      Related Diseases in Newborns.
AB  - The continuous evolution in preventive medicine has anointed vaccination a
      versatile, human-health improving tool, which has led to a steady decline in
      deaths in the developing world. Maternal immunization represents an incisive step
      forward for the field of vaccination as it provides protection against various
      life-threatening diseases in pregnant women and their children. A number of
      studies to improve prevention rates and expand protection against the largest
      possible number of infections are still in progress. The complex unicity of the
      mother-infant interaction, both during and after pregnancy and which involves
      immune system cells and molecules, is an able partner in the success of maternal
      immunization, as intended thus far. Interestingly, new studies have shed light on
      the versatility of maternal immunization in protecting infants from non
      infectious related diseases, such as allergy, asthma and congenital metabolic
      disorders. However, barely any attempt at applying maternal immunization to the
      prevention of childhood cancer has been made. The most promising study reported
      in this new field is a recent proof of concept on the efficacy of maternal
      immunization in protecting cancer-prone offspring against mammary tumor
      progression. New investigations into the possibility of exploiting maternal
      immunization to prevent the onset and/or progression of neuroblastoma, one of the
      most common childhood malignancies, are therefore justified. Maternal
      immunization is presented in a new guise in this review. Attention will be
      focused on its versatility and potential applications in preventing tumor
      progression in neuroblastoma-prone offspring.

PMID- 28763020
TI  - Influenza A Virus-Host Protein Interactions Control Viral Pathogenesis.
AB  - The influenza A virus (IAV), a member of the Orthomyxoviridae family, is a highly
      transmissible respiratory pathogen and represents a continued threat to global
      health with considerable economic and social impact. IAV is a zoonotic virus that
      comprises a plethora of strains with different pathogenic profiles. The different
      outcomes of viral pathogenesis are dependent on the engagement between the virus
      and the host cellular protein interaction network. The interactions may
      facilitate virus hijacking of host molecular machinery to fulfill the viral life
      cycle or trigger host immune defense to eliminate the virus. In recent years,
      much effort has been made to discover the virus-host protein interactions and
      understand the underlying mechanisms. In this paper, we review the recent
      advances in our understanding of IAV-host interactions and how these interactions
      contribute to host defense and viral pathogenesis.

PMID- 28763022
TI  - Characterization and Expression Profiling of Camellia sinensis Cinnamate 4
      hydroxylase Genes in Phenylpropanoid Pathways.
AB  - Cinnamate 4-hydroxylase (C4H), a cytochrome P450-dependent monooxygenase,
      participates in the synthesis of numerous polyphenoid compounds, such as
      flavonoids and lignins. However, the C4H gene number and function in tea plants
      are not clear. We screened all available transcriptome and genome databases of
      tea plants and three C4H genes were identified and named CsC4Ha, CsC4Hb, and
      CsC4Hc, respectively. Both CsC4Ha and CsC4Hb have 1518-bp open reading frames
      that encode 505-amino acid proteins. CsC4Hc has a 1635-bp open reading frame that
      encodes a 544-amino acid protein. Enzymatic analysis of recombinant proteins
      expressed in yeast showed that the three enzymes catalyzed the formation of p
      coumaric acid (4-hydroxy trans-cinnamic acid) from trans-cinnamic acid.
      Quantitative real-time PCR (qRT-PCR) analysis showed that CsC4Ha was highly
      expressed in the 4th leaf, CsC4Hb was highly expressed in tender leaves, while
      CsC4Hc was highly expressed in the young stems. The three CsC4Hs were induced
      with varying degrees by abiotic stress treatments. These results suggest they may
      have different subcellular localization and different physiological functions.

PMID- 28763024
TI  - Microwave-Assisted Pillaring of a Montmorillonite with Al-Polycations in
      Concentrated Media.
AB  - A montmorillonite has been intercalated with Al3+ polycations, using concentrated
      solutions and clay mineral dispersions. The reaction has been assisted by
      microwave radiation, yielding new intercalated solids and leading to Al-pillared
      solids after their calcination at 500  degrees C. The solids were characterized
      by elemental chemical analysis, X-ray diffraction, FTIR spectroscopy, thermal
      analyses, and nitrogen adsorption. The evolution of the properties of the
      materials was discussed as a function of the preparation conditions. Microwave
      treatment for 2.5 min provided correctly pillared solids.

PMID- 28763021
TI  - A Review of the Benefits of Nature Experiences: More Than Meets the Eye.
AB  - Evidence that experiences of nature can benefit people has accumulated rapidly.
      Yet perhaps because of the domination of the visual sense in humans, most
      research has focused on the visual aspects of nature experiences. However, humans
      are multisensory, and it seems likely that many benefits are delivered through
      the non-visual senses and these are potentially avenues through which a
      physiological mechanism could occur. Here we review the evidence around these
      lesser studied sensory pathways-through sound, smell, taste, touch, and three non
      sensory pathways. Natural sounds and smells underpin experiences of nature for
      many people, and this may well be rooted in evolutionary psychology. Tactile
      experiences of nature, particularly beyond animal petting, are understudied yet
      potentially fundamentally important. Tastes of nature, through growing and
      consuming natural foods, have been linked with a range of health and well-being
      benefits. Beyond the five senses, evidence is emerging for other non-visual
      pathways for nature experiences to be effective. These include ingestion or
      inhalation of phytoncides, negative air ions and microbes. We conclude that (i)
      these non-visual avenues are potentially important for delivering benefits from
      nature experiences; (ii) the evidence base is relatively weak and often based on
      correlational studies; and (iii) deeper exploration of these sensory and non
      sensory avenues is needed.

PMID- 28763023
TI  - Gastro-Esophageal Reflux in Children.
AB  - Gastro-esophageal reflux (GER) is common in infants and children and has a varied
      clinical presentation: from infants with innocent regurgitation to infants and
      children with severe esophageal and extra-esophageal complications that define
      pathological gastro-esophageal reflux disease (GERD). Although the
      pathophysiology is similar to that of adults, symptoms of GERD in infants and
      children are often distinct from classic ones such as heartburn. The passage of
      gastric contents into the esophagus is a normal phenomenon occurring many times a
      day both in adults and children, but, in infants, several factors contribute to
      exacerbate this phenomenon, including a liquid milk-based diet, recumbent
      position and both structural and functional immaturity of the gastro-esophageal
      junction. This article focuses on the presentation, diagnosis and treatment of
      GERD that occurs in infants and children, based on available and current
      guidelines.

PMID- 28763025
TI  - Effect of Sunlight Radiation on the Growth and Chemical Constituents of Salvia
      plebeia R.Br.
AB  - This study investigated the chemical composition changes of Salvia plebeia R.Br.
      cultivated under different light sources, including florescent light and
      sunlight. The plants were exposed to fluorescent light for four months and
      sunlight and then examined for the next 5-7 months. Plants were harvested monthly
      during the seven months, and we examined whether the difference in light source
      affected the phenolic and flavonoid contents and antioxidant activity. A simple
      and reliable HPLC method using a PAH C18 column was applied for the quantitative
      analysis of two triterpenoids from the S. plebeia groups. Oleanolic acid (OA) and
      ursolic acid (UA) showed good linearity (R2 > 0.9999) within the test ranges
      (0.005-0.05 mg/mL), and the average percentage recoveries of the OA and UA were
      95.1-104.8% and 97.2-107.1%, respectively. The intra- and inter-day relative
      standard deviations (RSDs) were less than 2.0%. After exposure to sunlight, the
      phenolic contents, including rosmarinic acid, showed a reduced tendency, whereas
      the flavonoid contents, including homoplantaginin and luteolin 7-glucoside, were
      increased. The content of the triterpenoids also showed an increased tendency
      under sunlight irradiation, but the variance was not larger than those of the
      phenolic and flavonoid contents. Among experimental groups, the group harvested
      at six months, having been exposed to sunlight for two months, showed the most
      potent antioxidant activity. Therefore, these results showed that the chemical
      composition and antioxidant activities of S. plebeia R.Br. was affected from
      environmental culture conditions, such as light source. Our studies will be
      useful for the development of functional materials using S. plebeia R.Br.

PMID- 28763027
TI  - Experimental Investigation on the Joining of Aluminum Alloy Sheets Using Improved
      Clinching Process.
AB  - Aluminum alloy sheets have been widely used to build the thin-walled structures
      by mechanical clinching technology in recent years. However, there is an exterior
      protrusion located on the lower sheet and a pit on the upper sheet, which may
      restrict the application of the clinching technology in visible areas. In the
      present study, an improved clinched joint used to join aluminum alloy sheets was
      investigated by experimental method. The improved clinching process used for
      joining aluminum alloy evolves through four phases: (a) localized deformation;
      (b) drawing; (c) backward extrusion; and (d) mechanical interlock forming. A flat
      surface can be produced using the improved clinching process. Shearing strength,
      tensile strength, material flow, main geometrical parameters, and failure mode of
      the improved clinched joint were investigated. The sheet material was compressed
      to flow radially and upward using a punch, which generated a mechanical interlock
      by producing severe localized plastic deformation. The neck thickness and
      interlock of the improved clinched joint were increased by increasing the forming
      force, which also contributed to increase the strength of the clinched joint. The
      improved clinched joint can get high shearing strength and tensile strength.
      Three main failure modes were observed in the failure process, which were neck
      fracture mode, button separation mode, and mixed failure mode. The improved
      clinched joint has better joining quality to join aluminum alloy sheets on the
      thin-walled structures.

PMID- 28763026
TI  - Genome-Wide Analysis Reveals Extensive Changes in LncRNAs during Skeletal Muscle
      Development in Hu Sheep.
AB  - As an important type of noncoding RNA molecules, long non-coding RNAs (lncRNAs)
      act as versatile players in various biological processes. However, little is
      known about lncRNA regulators during sheep muscle growth. To explore functional
      lncRNAs during sheep muscle growth, we systematically investigated lncRNAs using
      strand-specific Ribo-Zero RNA sequencing at three key developmental stages in Hu
      sheep. A total of 6924 lncRNAs were obtained, and the differentially expressed
      lncRNAs and genes were screened from (control vs. experiment) fetus vs. lamb,
      lamb vs. adult, and fetus vs. adult comparisons, respectively. The quantitative
      real-time polymerase chain reaction (qRT-PCR) analysis results correlated well
      with the sequencing data. Moreover, functional annotation analysis based on the
      Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases
      showed that the target genes of the differentially expressed lncRNAs were
      significantly enriched in organ morphogenesis, skeletal system development as
      well as response to stimulus and some other terms related to muscle. Furthermore,
      a co-expression network of the differentially expressed target genes and lncRNAs
      was constructed and well-known muscle growth regulators such as retrotransposon
      like 1 and Junctophilin-2 were included. Finally, we investigated the expression
      profiles of seven lncRNAs and their target genes, and found that they played
      vital roles in muscle growth. This study extends the sheep muscle lncRNA database
      and provides novel candidate regulators for future genetic and molecular studies
      on sheep muscle growth, which is helpful for optimizing the production of mutton.

PMID- 28763028
TI  - Rous Sarcoma Virus RNA Stability Element Inhibits Deadenylation of mRNAs with
      Long 3'UTRs.
AB  - All retroviruses use their full-length primary transcript as the major mRNA for
      Group-specific antigen (Gag) capsid proteins. This results in a long 3'
      untranslated region (UTR) downstream of the termination codon. In the case of
      Rous sarcoma virus (RSV), there is a 7 kb 3'UTR downstream of the gag terminator,
      containing the pol, env, and src genes. mRNAs containing long 3'UTRs, like those
      with premature termination codons, are frequently recognized by the cellular
      nonsense-mediated mRNA decay (NMD) machinery and targeted for degradation. To
      prevent this, RSV has evolved an RNA stability element (RSE) in the RNA
      immediately downstream of the gag termination codon. This 400-nt RNA sequence
      stabilizes premature termination codons (PTCs) in gag. It also stabilizes globin
      mRNAs with long 3'UTRs, when placed downstream of the termination codon. It is
      not clear how the RSE stabilizes the mRNA and prevents decay. We show here that
      the presence of RSE inhibits deadenylation severely. In addition, the RSE also
      impairs decapping (DCP2) and 5'-3' exonucleolytic (XRN1) function in knockdown
      experiments in human cells.

PMID- 28763029
TI  - An Opto-Electronic Sensor for Detecting Soil Microarthropods and Estimating Their
      Size in Field Conditions.
AB  - Methods to estimate density of soil-dwelling arthropods efficiently, accurately
      and continuously are critical for investigating soil biological activity and
      evaluating soil management practices. Soil-dwelling arthropods are currently
      monitored manually. This method is invasive, and time- and labor-consuming. Here
      we describe an infrared opto-electronic sensor for detection of soil
      microarthropods in the size range of 0.4-10 mm. The sensor is built in a novel
      microarthropod trap designed for field conditions. It allows automated, on-line,
      in situ detection and body length estimation of soil microarthropods. In the opto
      electronic sensor the light source is an infrared LED. Two plano-convex optical
      lenses are placed along the virtual optical axis. One lens on the receiver side
      is placed between the observation space at 0.5-1 times its focal length from the
      sensor, and another emitter side lens is placed between the observation space and
      the light source in the same way. This paper describes the setup and operating
      mechanism of the sensor and the control unit, and through basic tests it
      demonstrates its potential in automated detection of soil microarthropods. The
      sensor may be used for monitoring activities, especially for remote observation
      activities in soil and insect ecology or pest control.

PMID- 28763030
TI  - The Binding Effect of Proteins on Medications and Its Impact on Electrochemical
      Sensing: Antipsychotic Clozapine as a Case Study.
AB  - Clozapine (CLZ), a dibenzodiazepine, is demonstrated as the optimal antipsychotic
      for patients suffering from treatment-resistant schizophrenia. Like many other
      drugs, understanding the concentration of CLZ in a patient's blood is critical
      for managing the patients' symptoms, side effects, and overall treatment
      efficacy. To that end, various electrochemical techniques have been adapted due
      to their capabilities in concentration-dependent sensing. An open question
      associated with electrochemical CLZ monitoring is whether drug-protein complexes
      (i.e., CLZ bound to native blood proteins, such as serum albumin (SA) or alpha-1
      acid-glycoprotein (AAG)) contribute to electrochemical redox signals. Here, we
      investigate CLZ-sensing performance using fundamental electrochemical methods
      with respect to the impact of protein binding. Specifically, we test the activity
      of bound and free fractions of a mixture of CLZ and either bovine SA or human
      AAG. Results suggest that bound complexes do not significantly contribute to the
      electrochemical signal for mixtures of CLZ with AAG or SA. Moreover, the fraction
      of CLZ bound to protein is relatively constant at 31% (AAG) and 73% (SA) in
      isolation with varying concentrations of CLZ. Thus, electrochemical sensing can
      enable direct monitoring of only the unbound CLZ, previously only accessible via
      equilibrium dialysis. The methods utilized in this work offer potential as a
      blueprint in developing electrochemical sensors for application to other redox
      active medications with high protein binding more generally. This demonstrates
      that electrochemical sensing can be a new tool in accessing information not
      easily available previously, useful toward optimizing treatment regimens.

PMID- 28763031
TI  - Removal Efficiency and Risk Assessment of Polycyclic Aromatic Hydrocarbons in a
      Typical Municipal Wastewater Treatment Facility in Guangzhou, China.
AB  - The loading and removal efficiency of 16 US EPA polycyclic aromatic hydrocarbons
      (PAHs) were examined in an inverted A2/O wastewater treatment plant (WWTP)
      located in an urban area in China. The total PAH concentrations were 554.3 to
      723.2 ng/L in the influent and 189.6 to 262.7 ng/L in the effluent. The removal
      efficiencies of ?PAHs in the dissolved phase ranged from 63 to 69%, with the
      highest observed in naphthalene (80% removal). Concentration and distribution of
      PAHs revealed that the higher molecular weight PAHs became more concentrated with
      treatment in both the dissolved phase and the dewatered sludge. The sharpest
      reduction was observed during the pretreatment and the biological phase.
      Noncarcinogenic risk, carcinogenic risk, and total health risk of PAHs found in
      the effluent and sewage sludge were also assessed. The effluent BaP toxic
      equivalent quantities (TEQBaP) were above, or far above, standards in countries.
      The potential toxicities of PAHs in sewage effluent were approximately 10 to 15
      times higher than the acceptable risk level in China. The health risk associated
      with the sewage sludge also exceeded international recommended levels and was
      mainly contributed from seven carcinogenic PAHs. Given that WWTP effluent is a
      major PAH contributor to surface water bodies in China and better reduction
      efficiencies are achievable, the present study highlights the possibility of
      utilizing WWTPs for restoring water quality in riverine and coastal regions
      heavily impacted by PAHs contamination.

PMID- 28763032
TI  - A Chip for Estrogen Receptor Action: Detection of Biomarkers Released by MCF-7
      Cells through Estrogenic and Anti-Estrogenic Effects.
AB  - The fluorescence-based multi-analyte chip platform for the analysis of estrogenic
      and anti-estrogenic substances is a new in vitro tool for the high throughput
      screening of environmental samples. In contrast to existing tools, the chip
      investigates the complex action of xenoestrogens in a human cell model by
      characterizing protein expression. It allows for the quantification of 10
      proteins secreted by MCF-7 cells, representing various biological and
      pathological endpoints of endocrine action and distinguishing between estrogen-
      and anti-estrogen-dependent secretion of proteins. Distinct protein secretion
      patterns of the cancer cell line after exposure to known estrogen receptor
      agonists beta-estradiol, bisphenol A, genistein, and nonylphenol as well as
      antagonists fulvestrant and tamoxifen demonstrate the potential of the chip.
      Stimulation of cells with Interleukin-1beta shifts concentrations of low abundant
      biomarkers towards the working range of the chip. In the non-stimulated cell
      culture, Matrix Metalloproteinase 9 (MMP-9) and Vascular Endothelial Growth
      Factor (VEGF) show differences upon treatment with antagonists and agonists of
      the estrogen receptor. In stimulated MCF-7 cells challenged with receptor
      agonists secretion of Monocyte Chemoattractant Protein (MCP-1), Interleukin-6 (IL
      6), Rantes, and Interleukin-8 (IL-8) significantly decreases. In parallel, the
      proliferating effect of endocrine-disrupting substances in MCF-7 cells is
      assessed in a proliferation assay based on resazurin. Using ethanol as a solvent
      for test substances increases the background of proliferation and secretion
      experiments, while using dimethyl sulfoxide (DMSO) does not show any adverse
      effects. The role of the selected biomarkers in different physiological processes
      such as cell development, reproduction, cancer, and metabolic syndrome makes the
      chip an excellent tool for either indicating endocrine-disrupting effects in food
      and environmental samples, or for screening the effect of xenoestrogens on a
      cellular and molecular level.

PMID- 28763033
TI  - Chirality on Amorphous High-Tg Polymeric Nanofilms: Optical Activity
      Amplification by Thermal Annealing.
AB  - The chiroptical properties of amorphous chiral polymers functionalized with
      conjugated trans-azoaromatic chromophore linked to the backbone through a chiral
      cyclic pyrrolidine moiety of one single configuration at the solid state, as thin
      films, were investigated. For the first time nanometric thin films of amorphous
      polymers (not liquid crystals) showed a remarkable chiral amplification upon
      thermal treatment at a temperature close to their Tg. The side-chain azobenzene
      chromophores rearrangement driven by the enhanced chain mobility seems to favor
      the formation of nanodomains of conformationally ordered macromolecular chains
      with one prevailing helical handedness whose optical activity depends on the
      configuration of the intrinsic chirality of the monomeric units and which as a
      result are stable at room temperature for a long time.

PMID- 28763034
TI  - Deformation Monitoring of Metro Tunnel with a New Ultrasonic-Based System.
AB  - With the rapid construction of metro tunnels in many metropolises, a fast and
      convenient solution to capture tunnel deformation is desired by civil engineers.
      This contribution reports an automatic and wireless tunnel deformation monitoring
      system using ultrasonic transducers. A processing algorithm of the redundant
      ultrasonic information (RUI) approach is proposed to improve measurement
      accuracy. The feasibility of this tunnel deformation monitoring method is
      carefully examined with various probe angles, distances, and surrounding
      temperature variations. The results indicate that high accuracy can be achieved
      with different coefficients for various probe angles and sensor distances, as
      well as temperatures. In addition, a physical tunnel model was fabricated to
      verify the new processing algorithm of the RUI approach for a wireless tunnel
      deformation sensing system. The test results reveal that average measurement
      errors decreased from 7% to 3.75% using the RUI approach. Therefore, it can be
      concluded that the proposed approach is well suited to the automatic detection of
      critical conditions such as large deformation events in metro tunnels.

PMID- 28763035
TI  - A Motif in the F Homomorph of Rabbit Haemorrhagic Disease Virus Polymerase Is
      Important for the Subcellular Localisation of the Protein and Its Ability to
      Induce Redistribution of Golgi Membranes.
AB  - Rabbit haemorrhagic disease virus (RHDV) is a calicivirus that infects and
      frequently kills rabbits. Previously, we showed that the RHDV RNA-dependent RNA
      polymerase (RdRp) is associated with distinct, but yet uncharacterised
      subcellular structures and is capable of inducing a redistribution of Golgi
      membranes. In this study, we identified a partially hidden hydrophobic motif that
      determines the subcellular localisation of recombinant RHDV RdRp in transfected
      cells. This novel motif, 189LLWGCDVGVAVCAAAVFHNICY210, is located within the F
      homomorph, between the conserved F3 and A motifs of the core RdRp domain. Amino
      acid substitutions that decrease the hydrophobicity of this motif reduced the
      ability of the protein to accumulate in multiple subcellular foci and to induce a
      rearrangement of the Golgi network. Furthermore, preliminary molecular dynamics
      simulations suggest that the RHDV RdRp could align with the negatively charged
      surfaces of biological membranes and undergo a conformational change involving
      the F homomorph. These changes would expose the newly identified hydrophobic
      motif so it could immerse itself into the outer leaflet of intracellular
      membranes.

PMID- 28763037
TI  - Isolation and Tissue Distribution of an Insulin-Like Androgenic Gland Hormone
      (IAG) of the Male Red Deep-Sea Crab, Chaceon quinquedens.
AB  - The insulin-like androgenic gland hormone (IAG) found in decapod crustaceans is
      known to regulate sexual development in males. IAG is produced in the male
      specific endocrine tissue, the androgenic gland (AG); however, IAG expression has
      been also observed in other tissues of decapod crustacean species including
      Callinectes sapidus and Scylla paramamosain. This study aimed to isolate the full
      length cDNA sequence of IAG from the AG of male red deep-sea crabs, Chaceon
      quinquedens (ChqIAG), and to examine its tissue distribution. To this end, we
      employed polymerase chain reaction cloning with degenerate primers and 5' and 3'
      rapid amplification of cDNA ends (RACE). The full-length ChqIAG cDNA sequence
      (1555 nt) includes a 366 nt 5' untranslated region a 453 nt open reading frame
      encoding 151 amino acids, and a relatively long 3' UTR of 733 nt. The ORF
      consists of a 19 aa signal peptide, 32 aa B chain, 56 aa C chain, and 44 aa A
      chain. The putative ChqIAG amino acid sequence is most similar to those found in
      other crab species, including C. sapidus and S. paramamosain, which are clustered
      together phylogenetically.

PMID- 28763036
TI  - Evaluation of Taterapox Virus in Small Animals.
AB  - Taterapox virus (TATV), which was isolated from an African gerbil (Tatera kempi)
      in 1975, is the most closely related virus to variola; however, only the original
      report has examined its virology. We have evaluated the tropism of TATV in vivo
      in small animals. We found that TATV does not infect Graphiurus kelleni, a
      species of African dormouse, but does induce seroconversion in the Mongolian
      gerbil (Meriones unguiculatus) and in mice; however, in wild-type mice and
      gerbils, the virus produces an unapparent infection. Following intranasal and
      footpad inoculations with 1 * 106 plaque forming units (PFU) of TATV,
      immunocompromised stat1-/- mice showed signs of disease but did not die; however,
      SCID mice were susceptible to intranasal and footpad infections with 100%
      mortality observed by Day 35 and Day 54, respectively. We show that death is
      unlikely to be a result of the virus mutating to have increased virulence and
      that SCID mice are capable of transmitting TATV to C57BL/6 and C57BL/6 stat1-/-
      animals; however, transmission did not occur from TATV inoculated wild-type or
      stat1-/- mice. Comparisons with ectromelia (the etiological agent of mousepox)
      suggest that TATV behaves differently both at the site of inoculation and in the
      immune response that it triggers.

PMID- 28763038
TI  - Understanding Barriers to Participation in Cost-Share Programs For Pollinator
      Conservation by Wisconsin (USA) Cranberry Growers.
AB  - The expansion of modern agriculture has led to the loss and fragmentation of
      natural habitat, resulting in a global decline in biodiversity, including bees.
      In many countries, farmers can participate in cost-share programs to create
      natural habitat on their farms for the conservation of beneficial insects, such
      as bees. Despite their dependence on bee pollinators and the demonstrated
      commitment to environmental stewardship, participation in such programs by
      Wisconsin cranberry growers has been low. The objective of this study was to
      understand the barriers that prevent participation by Wisconsin cranberry growers
      in cost-share programs for on-farm conservation of native bees. We conducted a
      survey of cranberry growers (n = 250) regarding farming practices, pollinators,
      and conservation. Although only 10% of growers were aware of federal pollinator
      cost-share programs, one third of them were managing habitat for pollinators
      without federal aid. Once informed of the programs, 50% of growers expressed
      interest in participating. Fifty-seven percent of growers manage habitat for
      other wildlife, although none receive cost-share funding to do so. Participation
      in cost-share programs could benefit from outreach activities that promote the
      programs, a reduction of bureaucratic hurdles to participate, and technical
      support for growers on how to manage habitat for wild bees.

PMID- 28763039
TI  - Optimization Techniques for Design Problems in Selected Areas in WSNs: A
      Tutorial.
AB  - This paper is intended to serve as an overview of, and mostly a tutorial to
      illustrate, the optimization techniques used in several different key design
      aspects that have been considered in the literature of wireless sensor networks
      (WSNs). It targets the researchers who are new to the mathematical optimization
      tool, and wish to apply it to WSN design problems. We hence divide the paper into
      two main parts. One part is dedicated to introduce optimization theory and an
      overview on some of its techniques that could be helpful in design problem in
      WSNs. In the second part, we present a number of design aspects that we came
      across in the WSN literature in which mathematical optimization methods have been
      used in the design. For each design aspect, a key paper is selected, and for each
      we explain the formulation techniques and the solution methods implemented. We
      also provide in-depth analyses and assessments of the problem formulations, the
      corresponding solution techniques and experimental procedures in some of these
      papers. The analyses and assessments, which are provided in the form of comments,
      are meant to reflect the points that we believe should be taken into account when
      using optimization as a tool for design purposes.

PMID- 28763040
TI  - Strategies towards Improved Feed Efficiency in Pigs Comprise Molecular Shifts in
      Hepatic Lipid and Carbohydrate Metabolism.
AB  - Due to the central role of liver tissue in partitioning and metabolizing of
      nutrients, molecular liver-specific alterations are of considerable interest to
      characterize an efficient conversion and usage of feed in livestock. To deduce
      tissue-specific and systemic effects on nutrient metabolism and feed efficiency
      (FE) twenty-four animals with extreme phenotypes regarding residual feed intake
      (RFI) were analyzed. Transcriptome and fatty acid profiles of liver tissue were
      complemented with measurements on blood parameters and thyroid hormone levels.
      Based on 803 differentially-abundant probe sets between low- and high-FE animals,
      canonical pathways like integrin signaling and lipid and carbohydrate metabolism,
      were shown to be affected. Molecular alterations of lipid metabolism show a
      pattern of a reduced hepatic usage of fatty acids in high-FE animals.
      Complementary analyses at the systemic level exclusively pointed to increased
      circulating triglycerides which were, however, accompanied by considerably lower
      concentrations of saturated and polyunsaturated fatty acids in the liver of high
      FE pigs. These results are in accordance with altered muscle-to-fat ratios
      usually ascribed to FE animals. It is concluded that strategies to improve FE
      might favor a metabolic shift from energy storage towards energy utilization and
      mobilization.

PMID- 28763041
TI  - Using a Co-Creational Approach to Develop, Implement and Evaluate an Intervention
      to Promote Physical Activity in Adolescent Girls from Vocational and Technical
      Schools: A Case Control Study.
AB  - Background: As physical inactivity is particularly prevalent amongst lower
      educated adolescent girls, interventions are needed. Using a co-creational
      approach increases their engagement and might be effective. This study aimed to:
      (1) describe the co-creation process, (2) evaluate how girls experienced co
      creation, and (3) evaluate the effect of the co-creational interventions on
      physical activity, individual, sociocultural and school-based factors. Methods:
      Three intervention schools (n = 91) and three control schools (n = 105) across
      Flanders participated. A questionnaire was completed pre (September-October 2014)
      and post (April-May 2015). In between, sessions with a co-creation group were
      organised to develop and implement the intervention in each intervention school.
      Focus groups were conducted to evaluate the co-creational process. Results:
      School 1 organised sport sessions for girls, school 2 organised a fitness
      activity and set up a Facebook page, school 3 organised a lunch walk. Girls were
      positive about having a voice in developing an intervention. No significant
      effects were found, except for small effects on extracurricular sports
      participation and self-efficacy. Conclusions: Using a co-creational approach
      amongst adolescent girls might be a feasible approach. However, as interventions
      were minimal, effects were limited or undetectable. Future co-creation projects
      could consider the most optimal co-creation process, evaluation design and
      intensively test this approach.

PMID- 28763042
TI  - Optimization of a VOC Sensor with a Bilayered Diaphragm Using FBAR as Strain
      Sensing Elements.
AB  - Film bulk acoustic resonators (FBARs) are widely applied in mass bio-sensing and
      pressure sensors, owing to their extreme sensitivity and integration ability, and
      ability to miniaturize circuits. A volatile organic compound (VOC) sensor with a
      polymer-coated diaphragm, using FBARs as a strain sensing element is proposed and
      optimized. This vapor sensor is based on organic vapor-induced changes of
      mechanical deformation of the micro-diaphragm. The four FBARs are located at the
      edge of the bi-layer diaphragm comprising silicon nitride and silicon oxide for
      strain extraction. In this work, the strain distribution of the FBAR area under
      vapor loads is obtained using the finite element analysis (FEA) and the response
      frequency changes of the FBARs under vapor loads are obtained based on both the
      first-principle methods to deduce the elastic coefficient variation of aluminum
      nitride film in FBARs under the bending stresses and the Mason equivalent circuit
      model of the sensor using ADS software. Finally, optimizations are performed on
      both the bilayered diaphragm structure and sensing film. The diaphragm with a 0.7
      MUm silicon nitride layer and a 0.5 MUm silicon oxide layer are considered to be
      the optimized design. The optimal coverage area of the sensing film for the
      diaphragm is around 0.8.

PMID- 28763043
TI  - Impedance Matching Antenna-Integrated High-Efficiency Energy Harvesting Circuit.
AB  - This paper describes the design of a high-efficiency energy harvesting circuit
      with an integrated antenna. The circuit is composed of series resonance and boost
      rectifier circuits for converting radio frequency power into boosted direct
      current (DC) voltage. The measured output DC voltage is 5.67 V for an input of
      100 mV at 900 MHz. Antenna input impedance matching is optimized for greater
      efficiency and miniaturization. The measured efficiency of this antenna
      integrated energy harvester is 60% for -4.85 dBm input power and a load
      resistance equal to 20 kOmega at 905 MHz.

PMID- 28763045
TI  - mzStudio: A Dynamic Digital Canvas for User-Driven Interrogation of Mass
      Spectrometry Data.
AB  - Although not yet truly 'comprehensive', modern mass spectrometry-based
      experiments can generate quantitative data for a meaningful fraction of the human
      proteome. Importantly for large-scale protein expression analysis, robust data
      pipelines are in place for identification of un-modified peptide sequences and
      aggregation of these data to protein-level quantification. However, interoperable
      software tools that enable scientists to computationally explore and document
      novel hypotheses for peptide sequence, modification status, or fragmentation
      behavior are not well-developed. Here, we introduce mzStudio, an open-source
      Python module built on our multiplierz project. This desktop application provides
      a highly-interactive graphical user interface (GUI) through which scientists can
      examine and annotate spectral features, re-search existing PSMs to test different
      modifications or new spectral matching algorithms, share results with colleagues,
      integrate other domain-specific software tools, and finally create publication
      quality graphics. mzStudio leverages our common application programming interface
      (mzAPI) for access to native data files from multiple instrument platforms,
      including ion trap, quadrupole time-of-flight, Orbitrap, matrix-assisted laser
      desorption ionization, and triple quadrupole mass spectrometers and is compatible
      with several popular search engines including Mascot, Proteome Discoverer,
      X!Tandem, and Comet. The mzStudio toolkit enables researchers to create a digital
      provenance of data analytics and other evidence that support specific peptide
      sequence assignments.

PMID- 28763044
TI  - Tubulin Inhibitor-Based Antibody-Drug Conjugates for Cancer Therapy.
AB  - Antibody-drug conjugates (ADCs) are a class of highly potent biopharmaceutical
      drugs generated by conjugating cytotoxic drugs with specific monoclonal
      antibodies through appropriate linkers. Specific antibodies used to guide potent
      warheads to tumor tissues can effectively reduce undesired side effects of the
      cytotoxic drugs. An in-depth understanding of antibodies, linkers, conjugation
      strategies, cytotoxic drugs, and their molecular targets has led to the
      successful development of several approved ADCs. These ADCs are powerful
      therapeutics for cancer treatment, enabling wider therapeutic windows, improved
      pharmacokinetic/pharmacodynamic properties, and enhanced efficacy. Since tubulin
      inhibitors are one of the most successful cytotoxic drugs in the ADC
      armamentarium, this review focuses on the progress in tubulin inhibitor-based
      ADCs, as well as lessons learned from the unsuccessful ADCs containing tubulin
      inhibitors. This review should be helpful to facilitate future development of new
      generations of tubulin inhibitor-based ADCs for cancer therapy.

PMID- 28763047
TI  - Trending Longitudinal Agreement between Parent and Child Perceptions of Quality
      of Life for Pediatric Palliative Care Patients.
AB  - Pediatric palliative care studies often rely on proxy-reported instead of direct
      child-reported quality of life metrics. The purpose of this study was to
      longitudinally evaluate quality of life for pediatric patients receiving
      palliative care consultations and to compare patient-reported quality of life
      with parent perception of the child's quality of life across wellness domains.
      The 23-item PedsQLTM V4.0 Measurement Model was utilized for ten child and parent
      dyads at time of initial palliative care consultation, Month 6, and Month 12 to
      assess for physical, emotional, social, and cognitive dimensions of quality of
      life as reported independently by the child and by the parent for the child.
      Findings were analyzed using Bland-Altman plots to compare observed differences
      to limits of agreement. This study revealed overall consistency between parent-
      and child-reported quality of life across domains. Physical health was noted to
      be in closest agreement. At the time of initial palliative care consult, children
      collectively scored their social quality of life higher than parental perception
      of the child's social quality of life; whereas, emotional and cognitive quality
      of life domains were scored lower by children than by the parental report. At the
      one year survey time point, the physical, emotional, and social domains trended
      toward more positive patient perception than proxy perception with congruence
      between quality of life scores for the cognitive domain. Findings reveal the
      importance of eliciting a child report in addition to a parent report when
      measuring and longitudinally trending perceptions on quality of life.

PMID- 28763046
TI  - Increased Frequency of Rheumatoid Arthritis and Allergic Rhinitis among Pesticide
      Sprayers and Associations with Pesticide Use.
AB  - Objective: The aim of this study was to identify diseases linked with the
      pesticide sprayer occupation and explore possible associations with exposure
      history data. Methods: Alpha cross sectional study was conducted among pesticide
      sprayers (n = 80) and the general population (n = 90) in Thessaly (Greece).
      Medical history, demographic characteristics and detailed exposure history were
      recorded by conducting personal interviews. Lifetime exposure indicators were
      calculated for several pesticide chemical subclasses. Moreover, organophosphate
      metabolite levels were quantified in urine samples of all participants by using
      gas chromatography -mass spectrometry (GC-MS). Multinomial analysis was used to
      determine associations between occupational pesticide exposure and diseases or
      disorders. Results: In the pesticide sprayers group, significantly higher
      frequencies for rheumatoid arthritis (RA) and allergic rhinitis were observed
      compared with the control group (p = 0.002 and p = 0.024 respectively). Within
      the pesticide sprayers group, high lifetime pesticide exposure was associated
      with increased risk for reporting RA (OR: 43.07 95% CI: 3.09-600.67) and allergic
      rhinitis (OR: 9.72 95% CI: 2.31-40.89), compared with low pesticide exposure.
      Exposure to organophsphate, guanidine and quinone pesticides were associated with
      RA while organophosphates, pyrethroids and paraquat were associated with allergic
      rhinitis. Despite the higher levels of certain pesticide metabolites observed
      among participants with rheumatoid arthritis, the differences were not
      statistically significant. One metabolite (diethylthiophosphate) was found to be
      significantly increased in allergic rhinitis cases (p = 0.037). Conclusions: The
      results from the current study suggest a possible association of occupational
      pesticide exposure with RA and allergic rhinitis that should be further
      investigated.

PMID- 28763048
TI  - Outdoor Performance Analysis of a Photovoltaic Thermal (PVT) Collector with Jet
      Impingement and Compound Parabolic Concentrator (CPC).
AB  - This paper discusses the effect of jet impingement of water on a photovoltaic
      thermal (PVT) collector and compound parabolic concentrators (CPC) on electrical
      efficiency, thermal efficiency and power production of a PVT system. A prototype
      of a PVT solar water collector installed with a jet impingement and CPC has been
      designed, fabricated and experimentally investigated. The efficiency of the
      system can be improved by using jet impingement of water to decrease the
      temperature of the solar cells. The electrical efficiency and power output are
      directly correlated with the mass flow rate. The results show that electrical
      efficiency was improved by 7% when using CPC and jet impingement cooling in a PVT
      solar collector at 1:00 p.m. (solar irradiance of 1050 W/m2 and an ambient
      temperature of 33.5  degrees C). It can also be seen that the power output
      improved by 36% when using jet impingement cooling with CPC, and 20% without CPC
      in the photovoltaic (PV) module at 1:30 p.m. The short-circuit current ISC of the
      PV module experienced an improvement of ~28% when using jet impingement cooling
      with CPC, and 11.7% without CPC. The output of the PV module was enhanced by 31%
      when using jet impingement cooling with CPC, and 16% without CPC.

PMID- 28763049
TI  - Tetrabutylammonium Iodide-Promoted Thiolation of Oxindoles Using Sulfonyl
      Chlorides as Sulfenylation Reagents.
AB  - 3-Sulfanyloxindoles were synthesised by triphenylphosphine-mediated transition
      metal-free thiolation of oxindoles using sulfonyl chlorides as sulfenylation
      reagents. The above reaction was promoted by iodide anions, which was ascribed to
      the in situ conversion of sulfenyl chlorides into the more reactive sulfenyl
      iodides. Moreover, the thiolation of 3-aryloxindoles was facilitated by bases.
      The use of a transition-metal-free protocol, readily available reagents, and mild
      reaction conditions make this protocol more practical for preparing 3
      sulfanyloxindoles than traditional methods.

PMID- 28763050
TI  - 3D-Hydrogel Based Polymeric Nanoreactors for Silver Nano-Antimicrobial Composites
      Generation.
AB  - This study underscores the development of Ag hydrogel nanocomposites, as smart
      substrates for antibacterial uses, via innovative in situ reactive and reduction
      pathways. To this end, two different synthetic strategies were used. Firstly
      thiol-acrylate (PSA) based hydrogels were attained via thiol-ene and radical
      polymerization of polyethylene glycol (PEG) and polycaprolactone (PCL). As a
      second approach, polyurethane (PU) based hydrogels were achieved by condensation
      polymerization from diisocyanates and PCL and PEG diols. In fact, these syntheses
      rendered active three-dimensional (3D) hydrogel matrices which were used as
      nanoreactors for in situ reduction of AgNO3 to silver nanoparticles. A redox
      chemistry of stannous catalyst in PU hydrogel yielded spherical AgNPs formation,
      even at 4  degrees C in the absence of external reductant; and an appropriate
      thiol-functionalized polymeric network promoted spherical AgNPs well dispersed
      through PSA hydrogel network, after heating up the swollen hydrogel at 103 
      degrees C in the presence of citrate-reductant. Optical and swelling behaviors of
      both series of hydrogel nanocomposites were investigated as key factors involved
      in their antimicrobial efficacy over time. Lastly, in vitro antibacterial
      activity of Ag loaded hydrogels exposed to Pseudomona aeruginosa and Escherichia
      coli strains indicated a noticeable sustained inhibitory effect, especially for
      Ag-PU hydrogel nanocomposites with bacterial inhibition growth capabilities up to
      120 h cultivation.

PMID- 28763052
TI  - Corrigendum: Multimodal chest surface motion data for respiratory and
      cardiovascular monitoring applications.
AB  - This corrects the article DOI: 10.1038/sdata.2017.52.

PMID- 28763051
TI  - The ancestral flower of angiosperms and its early diversification.
AB  - Recent advances in molecular phylogenetics and a series of important
      palaeobotanical discoveries have revolutionized our understanding of angiosperm
      diversification. Yet, the origin and early evolution of their most characteristic
      feature, the flower, remains poorly understood. In particular, the structure of
      the ancestral flower of all living angiosperms is still uncertain. Here we report
      model-based reconstructions for ancestral flowers at the deepest nodes in the
      phylogeny of angiosperms, using the largest data set of floral traits ever
      assembled. We reconstruct the ancestral angiosperm flower as bisexual and
      radially symmetric, with more than two whorls of three separate perianth organs
      each (undifferentiated tepals), more than two whorls of three separate stamens
      each, and more than five spirally arranged separate carpels. Although uncertainty
      remains for some of the characters, our reconstruction allows us to propose a new
      plausible scenario for the early diversification of flowers, leading to new
      testable hypotheses for future research on angiosperms.

PMID- 28763053
TI  - Morphology of Dbx1 respiratory neurons in the preBotzinger complex and reticular
      formation of neonatal mice.
AB  - The relationship between neuron morphology and function is a perennial issue in
      neuroscience. Information about synaptic integration, network connectivity, and
      the specific roles of neuronal subpopulations can be obtained through
      morphological analysis of key neurons within a microcircuit. Here we present
      morphologies of two classes of brainstem respiratory neurons. First, interneurons
      derived from Dbx1-expressing precursors (Dbx1 neurons) in the preBotzinger
      complex (preBotC) of the ventral medulla that generate the rhythm for inspiratory
      breathing movements. Second, Dbx1 neurons of the intermediate reticular formation
      that influence the motor pattern of pharyngeal and lingual movements during the
      inspiratory phase of the breathing cycle. We describe the image acquisition and
      subsequent digitization of morphologies of respiratory Dbx1 neurons from the
      preBotC and the intermediate reticular formation that were first recorded in
      vitro. These data can be analyzed comparatively to examine how morphology
      influences the roles of Dbx1 preBotC and Dbx1 reticular interneurons in
      respiration and can also be utilized to create morphologically accurate
      compartmental models for simulation and modeling of respiratory circuits.

PMID- 28763054
TI  - An improved database of coastal flooding in the United Kingdom from 1915 to 2016.
AB  - Coastal flooding caused by extreme sea levels can produce devastating and wide
      ranging consequences. The 'SurgeWatch' v1.0 database systematically documents and
      assesses the consequences of historical coastal flood events around the UK. The
      original database was inevitably biased due to the inconsistent spatial and
      temporal coverage of sea-level observations utilised. Therefore, we present an
      improved version integrating a variety of 'soft' data such as journal papers,
      newspapers, weather reports, and social media. SurgeWatch2.0 identifies 329
      coastal flooding events from 1915 to 2016, a more than fivefold increase compared
      to the 59 events in v1.0. Moreover, each flood event is now ranked using a multi
      level categorisation based on inundation, transport disruption, costs, and
      fatalities: from 1 (Nuisance) to 6 (Disaster). For the 53 most severe events
      ranked Category 3 and above, an accompanying event description based upon the
      Source-Pathway-Receptor-Consequence framework was produced. Thus, SurgeWatch v2.0
      provides the most comprehensive and coherent historical record of UK coastal
      flooding. It is designed to be a resource for research, planning, management and
      education.

PMID- 28763056
TI  - Methanethiol-dependent dimethylsulfide production in soil environments.
AB  - Dimethylsulfide (DMS) is an environmentally important trace gas with roles in
      sulfur cycling, signalling to higher organisms and in atmospheric chemistry. DMS
      is believed to be predominantly produced in marine environments via microbial
      degradation of the osmolyte dimethylsulfoniopropionate (DMSP). However,
      significant amounts of DMS are also generated from terrestrial environments, for
      example, peat bogs can emit ~6 MUmol DMS m-2 per day, likely via the methylation
      of methanethiol (MeSH). A methyltransferase enzyme termed 'MddA', which catalyses
      the methylation of MeSH, generating DMS, in a wide range of bacteria and some
      cyanobacteria, may mediate this process, as the mddA gene is abundant in
      terrestrial metagenomes. This is the first study investigating the functionality
      of MeSH-dependent DMS production (Mdd) in a wide range of aerobic environments.
      All soils and marine sediment samples tested produced DMS when incubated with
      MeSH. Cultivation-dependent and cultivation-independent methods were used to
      assess microbial community changes in response to MeSH addition in a grassland
      soil where 35.9% of the bacteria were predicted to contain mddA. Bacteria of the
      genus Methylotenera were enriched in the presence of MeSH. Furthermore, many
      novel Mdd+ bacterial strains were isolated. Despite the abundance of mddA in the
      grassland soil, the Mdd pathway may not be a significant source of DMS in this
      environment as MeSH addition was required to detect DMS at only very low
      conversion rates.

PMID- 28763057
TI  - BECon: a tool for interpreting DNA methylation findings from blood in the context
      of brain.
AB  - Tissue differences are one of the largest contributors to variability in the
      human DNA methylome. Despite the tissue-specific nature of DNA methylation, the
      inaccessibility of human brain samples necessitates the frequent use of surrogate
      tissues such as blood, in studies of associations between DNA methylation and
      brain function and health. Results from studies of surrogate tissues in humans
      are difficult to interpret in this context, as the connection between blood-brain
      DNA methylation is tenuous and not well-documented. Here, we aimed to provide a
      resource to the community to aid interpretation of blood-based DNA methylation
      results in the context of brain tissue. We used paired samples from 16
      individuals from three brain regions and whole blood, run on the Illumina 450 K
      Human Methylation Array to quantify the concordance of DNA methylation between
      tissues. From these data, we have made available metrics on: the variability of
      cytosine-phosphate-guanine dinucleotides (CpGs) in our blood and brain samples,
      the concordance of CpGs between blood and brain, and estimations of how strongly
      a CpG is affected by cell composition in both blood and brain through the web
      application BECon (Blood-Brain Epigenetic Concordance;
      https://redgar598.shinyapps.io/BECon/). We anticipate that BECon will enable
      biological interpretation of blood-based human DNA methylation results, in the
      context of brain.

PMID- 28763055
TI  - Viral to metazoan marine plankton nucleotide sequences from the Tara Oceans
      expedition.
AB  - A unique collection of oceanic samples was gathered by the Tara Oceans
      expeditions (2009-2013), targeting plankton organisms ranging from viruses to
      metazoans, and providing rich environmental context measurements. Thanks to
      recent advances in the field of genomics, extensive sequencing has been performed
      for a deep genomic analysis of this huge collection of samples. A strategy based
      on different approaches, such as metabarcoding, metagenomics, single-cell
      genomics and metatranscriptomics, has been chosen for analysis of size
      fractionated plankton communities. Here, we provide detailed procedures applied
      for genomic data generation, from nucleic acids extraction to sequence
      production, and we describe registries of genomics datasets available at the
      European Nucleotide Archive (ENA, www.ebi.ac.uk/ena). The association of these
      metadata to the experimental procedures applied for their generation will help
      the scientific community to access these data and facilitate their analysis. This
      paper complements other efforts to provide a full description of experiments and
      open science resources generated from the Tara Oceans project, further extending
      their value for the study of the world's planktonic ecosystems.

PMID- 28763058
TI  - A novel preventive therapy for paclitaxel-induced cognitive deficits: preclinical
      evidence from C57BL/6 mice.
AB  - Chemotherapy-induced central nervous system (CNS) neurotoxicity presents an unmet
      medical need. Patients often report a cognitive decline in temporal correlation
      to chemotherapy, particularly for hippocampus-dependent verbal and visuo-spatial
      abilities. We treated adult C57Bl/6 mice with 12 * 20 mg kg-1 paclitaxel (PTX),
      mimicking clinical conditions of dose-dense chemotherapy, followed by a pulse of
      bromodesoxyuridine (BrdU) to label dividing cells. In this model, mice developed
      visuo-spatial memory impairments, and we measured peak PTX concentrations in the
      hippocampus of 230 nm l-1, which was sevenfold higher compared with the
      neocortex. Histologic analysis revealed a reduced hippocampal cell proliferation.
      In vitro, we observed severe toxicity in slowly proliferating neural stem cells
      (NSC) as well as human neuronal progenitor cells after 2 h exposure to low
      nanomolar concentrations of PTX. In comparison, mature post-mitotic hippocampal
      neurons and cell lines of malignant cells were less vulnerable. In PTX-treated
      NSC, we observed an increase of intracellular calcium levels, as well as an
      increased activity of calpain- and caspase 3/7, suggesting a calcium-dependent
      mechanism. This cell death pathway could be specifically inhibited with lithium,
      but not glycogen synthase kinase 3 inhibitors, which protected NSC in vitro. In
      vivo, preemptive treatment of mice with lithium prevented PTX-induced memory
      deficits and abnormal adult hippocampal neurogenesis. In summary, we identified a
      molecular pathomechanism, which invokes PTX-induced cytotoxicity in NSC
      independent of cell cycle status. This pathway could be pharmacologically
      inhibited with lithium without impairing paclitaxel's tubulin-dependent
      cytostatic mode of action, enabling a potential translational clinical approach.

PMID- 28763061
TI  - Interleukin33 deficiency causes tau abnormality and neurodegeneration with
      Alzheimer-like symptoms in aged mice.
AB  - This corrects the article DOI: 10.1038/tp.2017.142.

PMID- 28763059
TI  - Rare genetic variants in CX3CR1 and their contribution to the increased risk of
      schizophrenia and autism spectrum disorders.
AB  - CX3CR1, a G protein-coupled receptor solely expressed by microglia in the brain,
      has been repeatedly reported to be associated with neurodevelopmental disorders
      including schizophrenia (SCZ) and autism spectrum disorders (ASD) in
      transcriptomic and animal studies but not in genetic studies. To address the
      impacts of variants in CX3CR1 on neurodevelopmental disorders, we conducted
      coding exon-targeted resequencing of CX3CR1 in 370 Japanese SCZ and 192 ASD
      patients using next-generation sequencing technology, followed by a genetic
      association study in a sample comprising 7054 unrelated individuals (2653 SCZ,
      574 ASD and 3827 controls). We then performed in silico three-dimensional (3D)
      structural modeling and in vivo disruption of Akt phosphorylation to determine
      the impact of the detected variant on CX3CR1-dependent signal transduction. We
      detected a statistically significant association between the variant Ala55Thr in
      CX3CR1 with SCZ and ASD phenotypes (odds ratio=8.3, P=0.020). A 3D structural
      model indicated that Ala55Thr could destabilize the conformation of the CX3CR1
      helix 8 and affect its interaction with a heterotrimeric G protein. In vitro
      functional analysis showed that the CX3CR1-Ala55Thr mutation inhibited cell
      signaling induced by fractalkine, the ligand for CX3CR1. The combined data
      suggested that the variant Ala55Thr in CX3CR1 might result in the disruption of
      CX3CR1 signaling. Our results strengthen the association between microglia
      specific genes and neurodevelopmental disorders.

PMID- 28763060
TI  - BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and
      early stage amyloid neuropathology.
AB  - Lithium is first-line therapy for bipolar affective disorder and has recently
      been shown to have protective effects in populations at risk for Alzheimer's
      disease (AD). However, the mechanism underlying this protection is poorly
      understood and consequently limits its possible therapeutic application in AD.
      Moreover, conventional lithium formulations have a narrow therapeutic window and
      are associated with a severe side effect profile. Here we evaluated a novel
      microdose formulation of lithium, coded NP03, in a well-characterized rat model
      of progressive AD-like amyloid pathology. This formulation allows microdose
      lithium delivery to the brain in the absence of negative side effects. We found
      that NP03 rescued key initiating components of AD pathology, including
      inactivating GSK-3beta, reducing BACE1 expression and activity, and reducing
      amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter
      binding of synaptic plasticity genes and hippocampal neurogenesis. These results
      raise the possibility that NP03 be of therapeutic value in the early or
      preclinical stages of AD.

PMID- 28763062
TI  - Pathogen-mediated NMDA receptor autoimmunity and cellular barrier dysfunction in
      schizophrenia.
AB  - Autoantibodies that bind the N-methyl-D-aspartate receptor (NMDAR) may underlie
      glutamate receptor hypofunction and related cognitive impairment found in
      schizophrenia. Exposure to neurotropic pathogens can foster an autoimmune-prone
      environment and drive systemic inflammation leading to endothelial barrier
      defects. In mouse model cohorts, we demonstrate that infection with the protozoan
      parasite, Toxoplasma gondii, caused sustained elevations of IgG class antibodies
      to the NMDAR in conjunction with compromised blood-gut and blood-brain barriers.
      In human cohorts, NMDAR IgG and markers of barrier permeability were
      significantly associated with T. gondii exposure in schizophrenia compared with
      controls and independently of antipsychotic medication. Combined T. gondii and
      NMDAR antibody seropositivity in schizophrenia resulted in higher degrees of
      cognitive impairment as measured by tests of delayed memory. These data
      underscore the necessity of disentangling the heterogeneous pathophysiology of
      schizophrenia so that relevant subsets eligible for NMDAR-related treatment can
      be identified. Our data aid to reconcile conflicting reports regarding a role of
      pathological NMDAR autoantibodies in this disorder.

PMID- 28763063
TI  - Aripiprazole and Riluzole treatment alters behavior and neurometabolites in young
      ADHD rats: a longitudinal 1H-NMR spectroscopy study at 11.7T.
AB  - Attention deficit hyperactivity disorder (ADHD), Tourette syndrome (TS) as well
      as obsessive compulsive disorder (OCD) are co-occurring neurodevelopmental
      diseases that share alterations of frontocortical neurometabolites. In this
      longitudinal study we investigated the behavioral and neurochemical effects of
      aripiprazole and riluzole treatment in juvenile spontaneously hypertensive rats
      (SHR), a model for ADHD. For neurochemical analysis we employed in vivo magnetic
      resonance spectroscopy (MRS). Spectra from voxels located at the central striatum
      and prefrontal cortex were acquired postnatally from day 35 to 50. In the SHR
      strain only, treatments reduced repetitive grooming and climbing behavior. The
      absolute quantification of cerebral metabolites in vivo using localized 1H-MRS at
      11.7T showed significant alterations in SHR rats compared to controls (including
      glutamine, aspartate and total NAA). In addition, drug treatment reduced the
      majority of the detected metabolites (glutamate and glutamine) in the SHR brain.
      Our results indicate that the drug treatments might influence the hypothesized
      'hyperactive' state of the cortico-striatal-thalamo-cortical circuitries of the
      SHR strain. Furthermore, we could show that behavioral changes correlate with
      brain region-specific alterations in neurometabolite levels in vivo. These
      findings should serve as reference for animal studies and for the analysis of
      neurometabolites in selected human brain regions to further define neurochemical
      alterations in neuropsychiatric diseases.

PMID- 28763064
TI  - Strong seduction: impulsivity and the impact of contextual cues on instrumental
      behavior in alcohol dependence.
AB  - Alcohol-related cues acquire incentive salience through Pavlovian conditioning
      and then can markedly affect instrumental behavior of alcohol-dependent patients
      to promote relapse. However, it is unclear whether similar effects occur with
      alcohol-unrelated cues. We tested 116 early-abstinent alcohol-dependent patients
      and 91 healthy controls who completed a delay discounting task to assess choice
      impulsivity, and a Pavlovian-to-instrumental transfer (PIT) paradigm employing
      both alcohol-unrelated and alcohol-related stimuli. To modify instrumental choice
      behavior, we tiled the background of the computer screen either with conditioned
      stimuli (CS) previously generated by pairing abstract pictures with pictures
      indicating monetary gains or losses, or with pictures displaying alcohol or water
      beverages. CS paired to money gains and losses affected instrumental choices
      differently. This PIT effect was significantly more pronounced in patients
      compared to controls, and the group difference was mainly driven by highly
      impulsive patients. The PIT effect was particularly strong in trials in which the
      instrumental stimulus required inhibition of instrumental response behavior and
      the background CS was associated to monetary gains. Under that condition,
      patients performed inappropriate approach behavior, contrary to their previously
      formed behavioral intention. Surprisingly, the effect of alcohol and water
      pictures as background stimuli resembled that of aversive and appetitive CS,
      respectively. These findings suggest that positively valenced background CS can
      provoke dysfunctional instrumental approach behavior in impulsive alcohol
      dependent patients. Consequently, in real life they might be easily seduced by
      environmental cues to engage in actions thwarting their long-term goals. Such
      behaviors may include, but are not limited to, approaching alcohol.

PMID- 28763066
TI  - [The quality of a scientific publication is the product of a sum of efforts and
      attributes].
AB  - Todo editor de una publicacion medica cientifica busca que la revista que edita
      tenga o se reconozca con calidad. La calidad se logra mediante la participacion
      de un conjunto de profesionales (editores, autores, revisores, impresores,
      disenadores e incluso lectores) y los resultados de su participacion profesional
      agregan, durante el proceso, propiedades con la finalidad de que el producto, una
      publicacion medica cientifica, sea valorada por su calidad.

PMID- 28763065
TI  - Genome-wide association analysis identifies common variants influencing infant
      brain volumes.
AB  - Genome-wide association studies (GWAS) of adolescents and adults are transforming
      our understanding of how genetic variants impact brain structure and psychiatric
      risk, but cannot address the reality that psychiatric disorders are unfolding
      developmental processes with origins in fetal life. To investigate how genetic
      variation impacts prenatal brain development, we conducted a GWAS of global brain
      tissue volumes in 561 infants. An intronic single-nucleotide polymorphism (SNP)
      in IGFBP7 (rs114518130) achieved genome-wide significance for gray matter volume
      (P=4.15 * 10-10). An intronic SNP in WWOX (rs10514437) neared genome-wide
      significance for white matter volume (P=1.56 * 10-8). Additional loci with small
      P-values included psychiatric GWAS associations and transcription factors
      expressed in developing brain. Genetic predisposition scores for schizophrenia
      and ASD, and the number of genes impacted by rare copy number variants (CNV
      burden) did not predict global brain tissue volumes. Integration of these results
      with large-scale neuroimaging GWAS in adolescents (PNC) and adults (ENIGMA2)
      suggests minimal overlap between common variants impacting brain volumes at
      different ages. Ultimately, by identifying genes contributing to adverse
      developmental phenotypes, it may be possible to adjust adverse trajectories,
      preventing or ameliorating psychiatric and developmental disorders.

PMID- 28763067
TI  - [Myocardial infarction in young mexicans associated to metabolic syndrome].
AB  - BACKGROUND: Acute coronary diseases are catastrophic, especially in young
      patients. OBJECTIVE: To determine the risk of metabolic syndrome (MS) for
      premature acute myocardial infarction (AMI), combined with familial, behavioral,
      and nutritional factors in the northeast of Mexico. MATERIAL AND METHODS: This is
      a case control study of patients less than 47 years of age with no personal
      history of angina, AMI, or cerebrovascular disease. Cases corresponded to
      patients with AMI (incident and primary cases; n = 55) and controls were blood
      donors located at the same hospital (n = 55). Behavioral, nutritional, and
      cardiometabolic risk factors were measured. Multivariate logistic regression was
      used for estimating odds ratios (OR) and 95% confidence intervals (95% CI).
      RESULTS: MS increased the risk for premature AMI (95% CI: 1.73-39.5) eightfold,
      followed by smoking (OR: 7.76; 95% CI: 1.27-47.3), family history of AMI or
      sudden death (OR: 11.0; 95% CI: 2.03-60.4), and sedentary lifestyle (OR: 2.26;
      95% CI: 2.52-9.80), independent of potential confounders. CONCLUSIONS: The study
      highlights the magnitude of the risk of MS for AMI in Mexican young adults. The
      phenomenon of coronary diseases among young adults needs essential attention from
      the health sector.

PMID- 28763068
TI  - Experience in the corrective treatment of patients with atrioventricular septum.
AB  - INTRODUCTION: Atrioventricular septal defects are a wide spectrum of cardiac
      malformations, from partial until complete with one unique atrioventricular
      valve, atrioventricular valve communication, and leaky left heart valve. Its fast
      evolution to pulmonary vascular disease calls for early surgical management.
      Corrective treatment has a high percentage of re-operations and 8.6% mortality.
      OBJECTIVES: To describe the results of corrective treatments of atrioventricular
      septum defects in our institution's patients. MATERIALS AND METHODS:
      Observational, cross-sectional, analytical, and retrospective study of the
      atrioventricular septum defect patients during the period from March 2013 until
      March 2015. RESULTS: 51 atrioventricular septum defect patients were operated,
      nine with incomplete defect and 42 with complete defect, predominance type A of
      Rastell (35, 81.3%). Age at diagnosis was from 2.9 to 7.4 months; 82.3% of the
      patients have Down's syndrome. The cardiopathy with more association was the
      patient ductus arteriosus in 61.9% of cases. Average stay in intensive care was
      3.8-9.9 days. Eight (15.6%) patients died. CONCLUSION: Diagnosis and surgical
      treatment of atrioventricular septum defects in our institution it is made early.
      Results from surgical correction are comparable to that reported in the
      international literature.

PMID- 28763069
TI  - [Risk factors associated with the development of early neurological complications
      in purulent meningitis in a pediatric population].
AB  - OBJECTIVE: To determine the risk factors associated with the development of early
      neurological complications in purulent meningitis in a pediatric population.
      METHODS: This was a case-control study including 78 children aged one month to 16
      years with purulent meningitis divided into two groups: cases, with early
      neurological complications (defined as those presenting < 72 hours from
      initiation of clinical manifestation), and controls, without early neurological
      complications. Clinical, serum laboratory, and cerebrospinal fluid (CSF).
      RESULTS: Seventy-eight patients were included: cases, n = 33, and controls, n =
      45. Masculine gender, 19 (57%) vs. feminine gender, 28 (62%) (p = 0.679). Median
      age in months, 36 months (range, 1-180) vs. 12 months (range, 1-168) (p = 0.377).
      Factors associated with neurological complications: convulsive crises on
      admission, p = 0.038, OR, 2.65 (range, 1.04-6.74); meningeal signs, p = 0.032,
      OR, 2.73 (range, 1.07-6.96); alteration of the alert state, p = 0.003, OR, 13.0
      (range, 1.64-105.3); orotracheal intubation, p = 0.000, OR, 14.47 (range, 4.76
      44.01); neurological deterioration, p = 0.000, OR, 9.60 (range, 3.02-30.46);
      turbid CSF, p = 0.003, OR, 4.20 (range, 1.57-11.20); hypoglycorrhachia, < 30
      mg/dl, p = 0.001, OR, 9.2 (range, 3.24-26.06); and positive CSF culture, p =
      0.001, OR, 16.5 (range, 1.97-138.1). CONCLUSIONS: The factors associated with
      early neurological complications included convulsive crises on admission,
      meningeal signs, alteration of the alert state, need for orotracheal intubation,
      turbid CSF, hypoglycorrhachia, and positive CSF culture.

PMID- 28763070
TI  - [Knowledge of vector-borne diseases (dengue, rickettsiosis and Chagas disease) in
      physicians].
AB  - BACKGROUND: The ecological conditions of Yucatan made it a suitable region for
      the acquisition of vector-borne diseases such as dengue, rickettsiosis, and
      Chagas disease. As the epidemiological burden of these diseases shows an alarming
      increase of severe cases, the early establishment of diagnosis and therapeutics
      by first-contact physicians is a critical step that is not being fulfilled due to
      several reasons, including poor knowledge. OBJECTIVE: To determine the level of
      knowledge related to dengue, Chagas disease, and rickettsiosis among rural first
      contact physicians of Yucatan. METHODS: A survey was applied to 90 first-contact
      physicians from rural clinics of Yucatan, which included 32 items related to the
      diagnosis, treatment, and prevention of dengue, rickettsiosis, and Chagas
      disease. Answers were analyzed by central tendency statistics. RESULTS:
      Differences were observed among every category, however; diagnosis and
      therapeutics showed the lower values. Globally, 62.5% of respondents showed
      moderate knowledge, 37.5% poor knowledge, and 0% adequate knowledge. DISCUSSION:
      Results suggest that a strong campaign for a continuous diffusion of knowledge
      regarding these diseases is needed. In regions with high prevalence of these
      kinds of diseases, like Yucatan, the impact of these results on the
      epidemiological burden of these diseases must be evaluated.

PMID- 28763071
TI  - Prevalence of respiratory viruses in wheezing children not older than 24 months
      of age.
AB  - INTRODUCTION: Wheezing in children not older than 24 months of age is a frequent
      event, and viruses are usually the causative agents. The aim of the study was to
      estimate the prevalence of respiratory viruses in wheezing children who were not
      older than 24 months of age and who had no history of asthma. METHODS: Fifty-five
      Mexican children were included in an analytical cross-sectional study. Nasal
      secretions were obtained by using sterile rayon-tipped applicators to identify
      the virus by polymerase chain reaction or reverse transcription-polymerase chain
      reaction: adenovirus, bocavirus, human rhinovirus, influenza virus type A, human
      metapneumovirus, parainfluenza, rhinovirus, and respiratory syncytial virus. The
      prevalence of viral etiology was estimated by dividing the frequency of the
      identified virus by the number of participants. Ninety-five percent confidence
      intervals for proportions were calculated. RESULTS: Most of the patients were
      male (35/55, 63.6%). The average time of evolution of wheezing episode was 3
      days. The third part of enrolled population were receiving antibiotics.
      Respiratory viruses were detected in 33 (60%; 95% CI: 46.8-71.9%) out of 55
      cases, and viral coinfection was detected in five cases (9.1%; 95% CI: 3.5
      19.9%). Human metapneumovirus was the most frequently identified virus (23.6%),
      followed by bocavirus (14.5%), respiratory syncytial virus and rhinovirus (12.7%
      each), and to a lesser extent influenza virus type A and parainfluenza.
      Rhinovirus was the predominant virus in outpatient children (28.6%). In the
      inpatient emergency room and inhalotherapy room, human metapneumovirus
      predominated (41.2 and 16.1%, respectively). CONCLUSION: bocavirus and human
      metapneumovirus were the most frequently identified viruses in Mexican children
      who were < 2 years of age, suffered from wheezing, and had no history of asthma.

PMID- 28763073
TI  - [Construction and validation of the "La Salle Instrument" to evaluate the ethical
      aspects in biomedical research on human beings].
AB  - INTRODUCTION: Research projects must demonstrate not only a rigorous scientific
      methodology, but also the ethical aspects that require profound reflection of the
      reviewers. Current regulations establish criteria for research projects on human
      health, but many of these aspects are subjective. How can the evaluation of such
      projects be standardized? This is the main subject of the current project.
      MATERIALS AND METHODS: This project comprises two phases. First, the design and
      construction of an instrument of evaluation based on the fundamental principles
      of bioethics, which are autonomy, beneficence, non-maleficence, and justice, and
      other aspects. The second phase consists of content validation through expert.
      RESULTS: During the phase of reviewing the instrument, it was necessary to make
      changes by adding, removing, or changing the concepts or criteria, which lead to
      the construction of the second version of the format. This new instrument was
      reviewed and analyzed by using the AGREE II instrument, and this version was
      validated by experts by greater than 95%. CONCLUSIONS: There are some
      recommendations to analyze the ethical aspects in research protocols involving
      human subjects, but they define the concepts and criteria to be evaluated. By
      presenting the criteria to be evaluated individually, the "La Salle instrument"
      allows the evaluation to be more objective and standardized.

PMID- 28763072
TI  - [Diagnostico tardio de psoriasis: motivos y consecuencias].
AB  - BACKGROUND: Psoriasis is an autoimmune skin disease that may be associated with
      articular manifestations, and the most common clinical presentation is the
      variety "in plaques". In Mexico, in the Centro Dermatologico Pascua, it is the
      eighth leading cause of consultation. The aim of this study was to determine the
      diagnostic process of patients in a reference center for diseases of the skin.
      METHODS: Performing an analytical cross-sectional study that included 100
      patients where the diagnostic process was questioned, clinimetric scales were
      applied and evaluated anthropometric. RESULTS: It was found that 70% of patients
      had taken over a month to get medical care (median: 3 months; IQR: 11 months),
      having consulted in 61% to a general physician as a doctor of first contact and
      89% being diagnosed by a dermatologist. Eighty-eight percent of the patients were
      overweight or obese. We found as a factor of delay, a partnership with the
      variable of having an Institutional Medical Service (p = 0.019; U = 695.5).
      CONCLUSION: it is necessary to design a system to shorten the diagnostic process,
      not only in psoriasis, in addition to emphasizing dermatological education.

PMID- 28763074
TI  - Nanodevices that acts as nanocarriers for controlled and directed drug delivery
      to select cells, organs or tissues in cardiovascular diseases.
AB  - Cardiovascular disease, which today represents the main cause of death worldwide,
      is a likely candidate for the application of nanotechnology in the near future.
      Nanocarriers are currently being developed to deliver medicine (smart drugs) to
      selected targets in cells and tissues of blood vessels and the heart, as well as
      to aid in diagnosis and screening for early detection and individualized
      treatment. Other applications of nanotechnology hold promise for the long run,
      such as using nanodevices for drug delivery or correcting the misfolding of
      proteins. With super-potent effects, nanoparticles should be able to evoke
      therapeutic effects at a lower dose and for longer periods. The development of
      nanodevices and nanocarriers must take an integral approach that considers many
      properties-physical, chemical, biological, biochemical, anatomical,
      morphological, physiological, pharmacological, toxicological, mechanical,
      electrical, magnetic, thermodynamic, and optical-in order to evaluate
      biocompatibility and therefore avoid toxicological and/or other adverse effects.
      Intensified research in relation to nanocarriers and other nanotechnology could
      help reduce morbidity and mortality in cardiovascular disease.

PMID- 28763075
TI  - [Group B streptococcal perinatal infection: A Global, Latin American and Mexican
      Overview].
AB  - Group B streptococci (Streptococcus agalactiae) cause a number of infections in
      women during pregnancy and postpartum, such as urinary tract infection,
      chorioamnionitis and endometritis, consequently may affect the newborn. Group B
      streptococci is the most common cause of severe infections in newborns in
      developed countries. Studies on the epidemiology of group B streptococci
      infections in Latin America are still limited. This information is also unknown
      in Mexico, but studies carried out in the center of the country have found high
      rates of vaginal colonization in pregnant women and there are case series and
      case reports of newborns. Microbiological and molecular epidemiology studies in
      Mexico have shown that populations of group B streptococci have a clonal
      distribution and that there are clones with genetic and phenotypic
      characteristics of high virulence that appear to be responsible for most of
      perinatal pathology. However, the actual role of group B streptococci in
      perinatal pathology in Mexico is unknown. Consequently, whether to perform or not
      the screening for determining the group B streptococci colonization status in
      pregnant women, and the indication or not for intrapartum antibiotic prophylaxis
      to prevent neonatal group B streptococci infection in Mexico, are still
      controversial.

PMID- 28763076
TI  - [Study Plan 2016 of the licentiate of medical surgery of the faculty of higher
      studies iztacala].
AB  - The 2016 undergraduate medical degree curriculum at the Facultad de Estudios
      Superiores Iztacala of the Universidad Nacional Autonoma de Mexico (UNAM) is
      presented. It is the result of a long institutional reflection and academic
      dialog process of approximately three years, which culminated in its approval by
      UNAM's Academic Council for the Biology, Chemistry, and Health Sciences areas on
      January 25, 2016. Its most relevant characteristics are: modular organization,
      four knowledge areas (biomedical, methodological, socio-psychological, and
      humanistic and medical practice), and new modules such as Seminar of socio-psycho
      biological integration; Genetics and molecular biology; Biochemistry and cellular
      biology; Pharmacological basis of therapeutics; Infectious diseases, microbiology
      and parasitology; Medical ethics; Public health; and Evidence-based medicine -
      clinical epidemiology. To achieve a more flexible curriculum, optional modules
      were included. To make possible the curricular change, improving the teaching
      strategies, innovating the learning assessment methods, supporting the training
      and updating of the teaching staff, and establishing a curriculum development
      committee for following up and evaluating the program, are necessary. Curricular
      changes are difficult and complex processes; they suppose challenges and
      opportunities. It is mandatory to plan them carefully and sensitively to allow a
      successful transition and avoid conflicts for the students, the teachers and the
      institution.

PMID- 28763077
TI  - [National Academy of Medicine, one hundred and fifty-four academic year].
AB  - El incalculable valor que atesora la Academia Nacional de Medicina, su enorme
      influencia y repercusion sobre la toma de decisiones medico-cientifico
      epidemiologicas, radica unica y exclusivamente en el dominio del conocimiento, la
      mente cientifica y el talento de todos y cada uno de sus miembros, desde su
      fundacion en 1864 hasta nuestros dias.

PMID- 28763078
TI  - [Conference Dr. Ignacio Chavez. Moving towards molecular medicine].
AB  - El solo nombre del Dr. Ignacio Chavez y la calidad academica de los que me han
      precedido me hacen sentir emocionado, consciente de que me encuentro sobre los
      hombros de grandes aportadores a nuestra medicina.

PMID- 28763080
TI  - [Leadership and CETREMI].
AB  - Segun la Real Academia Espanola, el termino "lider" significa "persona que dirige
      u orienta a un grupo, que reconoce su autoridad". Es importante este termino ya
      que es muy ambiguo, porque no reconoce el nivel moral o la empatia que puede
      ejercer una persona en determinado grupo al reconocerlo como lider, y no solo con
      la autoridad que este puede ejercer en el mismo, siendo este ultimo concepto algo
      muy comun en el mundo anglosajon, denominandose lider a alguien que tiene un
      puesto de autoridad, lo cual se puede confundir con lo que conocemos como "jefe".

PMID- 28763079
TI  - [Medical movement in Mexico. To 50 years. Open file].
AB  - Gutierrez-Samperio hace una excelente narrativa del movimiento denominado
      "blanco" hace medio siglo, encabezado por medicos y otros trabajadores de salud,
      principalmente enfermeras. Es importante revisar los logros y limitaciones que
      dicho fenomeno alcanzo. Por ejemplo, actualmente el residente que cursa una
      especialidad cuenta con un reconocimiento institucional, universitario y de
      profesiones al termino de su formacion, ademas de tener una beca economica
      (probablemente insuficiente) y dias de vacaciones programados.

PMID- 28763081
TI  - [Internal Medicine in the curriculum of General Medicine at Universities of
      Mexico, 2014].
AB  - The aim of this study was to analyze Internal Medicine as a subject and its
      requirement in each of the Universities curriculum in Mexico that offers a degree
      in General Medicine. By the end of the first quarter of 2014, the research was
      closed and 81 campuses were studied. This research was quantitative, using an
      analytical technique, written discourse, exploratory and purposive sampling not
      random and homogeneous type. The Likert questionnaire was used in this study to
      analyse the following variables: the record of Internal Medicine as a subject,
      the burden of credit, and the location of the program. The procedure consisted of
      three phases. First obtaining an official list of all the Universities in the
      Mexican Association of Colleges and Schools of Medicine. Second, obtaining an
      analysis of each of the Universities' curriculums, and lastly gathering each
      variable of the study. The results of the Universities were 63% were public and
      37% private. Internal Medicine as a subject in the curriculum was 37.1%, and 20%
      of the universities include it for six months and 9% offer it the whole year.
      However, the undergraduate internship in Internal Medicine offers it 100%. In
      conclusion, Internal Medicine as a subject could disappear from the curriculum in
      General Medicine before coming to the undergraduate internship, even though the
      latter is declared required in hospital shifts.

PMID- 28763082
TI  - [Effectiveness of dexamethasone as an adjuvant in preemptive analgesia for
      postoperative pain in patients undergoing abdominal surgery].
AB  - OBJECTIVE: To determine the effectiveness of adjuvant dexamethasone in preemptive
      analgesia for postoperative pain in patients undergoing abdominal surgery.
      MATERIALS AND METHODS: This was an experimental, comparative, prospective and
      longitudinal study. It included 92 patients scheduled for elective abdominal
      surgery, who participated with prior informed consent. They were divided in two
      groups of 46 patients. For statistical analysis of results, we used descriptive
      statistics and Chi square and Student t. RESULTS: 92 patients were evaluated with
      an average age of 47 years; 15% corresponded to ASA I, 56% ASA II, and 21% ASA
      III. With the visual analog scale (VAS), it was possible to observe that the mean
      difference between the groups was 0.91; both groups showed a minimum of zero and
      a maximum eight points. In comparison, we obtained p < 0.05 at the first hour,
      second hour, and at 24 hours of VAS assessment. CONCLUSION: Dexamethasone better
      controlled postsurgical pain and had adequate hemodynamic stability.

PMID- 28763083
TI  - [Squamous cell carcinoma in situ of the cervix and placental site nodule: Case
      report].
AB  - An asymptomatic 24-year-old woman underwent a colposcopy, cervical biopsy, and
      subsequently, a conization for a cervical squamous cell carcinoma in situ with
      glandular extension. Simultaneously, an endometrial biopsy was carried out in
      which, incidentally, a placental site nodule was diagnosed, a rare non-neoplastic
      lesion originating in the intermediate trophoblast. Given the coexistence of
      these two entities, it was necessary to make a differential diagnosis between
      them and also with other pathologies of the trophoblast such as an exaggerated
      placental site, placental site trophoblastic tumor, and epithelioid trophoblastic
      tumor.

PMID- 28763084
TI  - [Tuberculous abscess of the thoracic wall secondary to nodular tuberculosis:
      Atypical presentation in an older adult].
AB  - Tuberculosis (tb) of the chest wall is uncommon and it represents less than 5% of
      all cases of musculoskeletal tb and only 1-2% of tb. We present the case of an
      elderly woman with tb of the chest wall secondary to a nodal tb with an unusual
      presentation. The diagnosis of this entity is difficult because the disease often
      mimics other diseases such as pyogenic abscess, chest wall.

PMID- 28763085
TI  - [Dr. Raul Gonzalez Enriquez and the Establishment of the Latin American
      Psychiatric Association].
AB  - At the first World Psychiatry Congress (Paris, 1950), the Mexican doctor Raul
      Gonzalez Enriquez (1906-1952), at his own proposal and motion, created the Latin
      American Psychiatric Association (APAL), and the next year, between December 8th
      and 11th, 1951, with two branch offices already established in Mexico City and
      Jalapa, Veracruz, held the first APAL Congress, attended by delegates from 14
      countries. That first Congress and the efforts of the founder have been
      maliciously dismissed in the annals of Hispanic American psychiatric history;
      thus, it is necessary to account for the events that passed, with the purpose of
      reclaiming the commendable work of such a distinguished, internationally renown
      psychiatrist.

PMID- 28763092
TI  - ?

PMID- 28763086
TI  - [Chemistry and Pharmacy in the Journal of the Academy of Medical Medicine (1836
      1843)].
AB  - This paper analyzes the articles published on chemicals and pharmaceuticals in
      the Periodico de la Academia de Medicina de Megico. Through these publications it
      is possible to illustrate the transformation in the study of medical material of
      the era. At the same time, it shows discussions held by doctors and pharmacists
      about scientific news and analysis of local therapeutic resources.

PMID- 28763093
TI  - ?

PMID- 28763094
TI  - ?

PMID- 28763095
TI  - ?

PMID- 28763096
TI  - ?
AB  - Access to rapid laboratory analytical services in cases of acute poisoning
      provides better and safer patient care The Swedish Poisons Information Centre, a
      nationwide 24/7 service to healthcare providers and the public, answers many
      questions about serious cases of acute poisoning. In some of these, prompt and
      proper treatment recommendations can be crucial for the clinical outcome. In
      cases where self-reported information is missing or considered unreliable, more
      emphasis is placed on the clinical symptoms and results of toxicological
      analyses. However, rapid access to toxicological analysis for the most common set
      of poisoning agents varies between hospitals and laboratories. A priority list of
      toxic agents for which improved analytical techniques could offer a more
      widespread availability and rapid access to clinically important test results is
      presented.

PMID- 28763098
TI  - Cross-species comparison of behavioral neurodevelopmental milestones in the
      common marmoset monkey and human child.
AB  - The common marmoset (Callithrix jacchus) is an increasingly popular non-human
      primate species for developing transgenic and genomic edited models of
      neurological disorders. These models present an opportunity to assess from birth
      the impact of genetic mutations and to identify candidate predictive biomarkers
      of early disease onset. In order to apply findings from marmosets to humans, a
      cross-species comparison of typical development is essential. Aiming to identify
      similarities, differences, and gaps in knowledge of neurodevelopment, we
      evaluated peer-reviewed literature focused on the first 6 months of life of
      marmosets and compared to humans. Five major developmental constructs, including
      reflexes and reactions, motor, feeding, self-help, and social, were compared.
      Numerous similarities were identified in the developmental sequences with
      differences often influenced by the purpose of the behavior, specifically for
      marmoset survival. The lack of detailed knowledge of marmoset development was
      exposed as related to the vast resources for humans.

PMID- 28763099
TI  - Autologous tolerogenic dendritic cells derived from monocytes of systemic lupus
      erythematosus patients and healthy donors show a stable and immunosuppressive
      phenotype.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease with unrestrained T
      cell and B-cell activity towards self-antigens. Evidence shows that apoptotic
      cells (ApoCells) trigger an autoreactive response against nuclear antigens in
      susceptible individuals. In this study, we focus on generating and characterizing
      tolerogenic dendritic cells (tolDCs) to restore tolerance to ApoCells. Monocyte
      derived dendritic cells (DCs) from healthy controls and patients with SLE were
      treated with dexamethasone and rosiglitazone to induce tolDCs. Autologous
      apoptotic lymphocytes generated by UV irradiation were given to tolDCs as a
      source of self-antigens. Lipopolysaccharide (LPS) was used as a maturation
      stimulus to induce the expression of co-stimulatory molecules and secretion of
      cytokines. TolDCs generated from patients with SLE showed a reduced expression of
      co-stimulatory molecules after LPS stimulation compared with mature DCs. The same
      phenomenon was observed in tolDCs treated with ApoCells and LPS. In addition,
      ApoCell-loaded tolDCs stimulated with LPS secreted lower levels of interleukin-6
      (IL-6) and IL-12p70 than mature DCs without differences in IL-10 secretion. The
      functionality of tolDCs was assessed by their capacity to prime allogeneic T
      cells. TolDCs displayed suppressor properties as demonstrated by a significantly
      reduced capacity to induce allogeneic T-cell proliferation and activation.
      ApoCell-loaded tolDCs generated from SLE monocytes have a stable
      immature/tolerogenic phenotype that can modulate CD4+ T-cell activation. These
      properties make them suitable for an antigen-specific immunotherapy for SLE.

PMID- 28763097
TI  - Obesity and adverse breast cancer risk and outcome: Mechanistic insights and
      strategies for intervention.
AB  - Answer questions and earn CME/CNE Recent decades have seen an unprecedented rise
      in obesity, and the health impact thereof is increasingly evident. In 2014,
      worldwide, more than 1.9 billion adults were overweight (body mass index [BMI],
      25-29.9 kg/m2 ), and of these, over 600 million were obese (BMI >=30 kg/m2 ).
      Although the association between obesity and the risk of diabetes and coronary
      artery disease is widely known, the impact of obesity on cancer incidence,
      morbidity, and mortality is not fully appreciated. Obesity is associated both
      with a higher risk of developing breast cancer, particularly in postmenopausal
      women, and with worse disease outcome for women of all ages. The first part of
      this review summarizes the relationships between obesity and breast cancer
      development and outcomes in premenopausal and postmenopausal women and in those
      with hormone receptor-positive and -negative disease. The second part of this
      review addresses hypothesized molecular mechanistic insights that may underlie
      the effects of obesity to increase local and circulating proinflammatory
      cytokines, promote tumor angiogenesis and stimulate the most malignant cancer
      stem cell population to drive cancer growth, invasion, and metastasis. Finally, a
      review of observational studies demonstrates that increased physical activity is
      associated with lower breast cancer risk and better outcomes. The effects of
      recent lifestyle interventions to decrease sex steroids, insulin/insulin-like
      growth factor-1 pathway activation, and inflammatory biomarkers associated with
      worse breast cancer outcomes in obesity also are discussed. Although many
      observational studies indicate that exercise with weight loss is associated with
      improved breast cancer outcome, further prospective studies are needed to
      determine whether weight reduction will lead to improved patient outcomes. It is
      hoped that several ongoing lifestyle intervention trials, which are reviewed
      herein, will support the systematic incorporation of weight loss intervention
      strategies into care for patients with breast cancer. CA Cancer J Clin
      2017;67:378-397. (c) 2017 American Cancer Society.

PMID- 28763102
TI  - Resistance to Hydrogen Peroxide Highlights Gymnodinium catenatum (Dinophyceae)
      Sensitivity to Geomagnetic Activity.
AB  - The chain-forming dinoflagellate Gymnodinium catenatum was exposed to hydrogen
      peroxide. Microscopical examination revealed striking dose-response alterations
      in chain formation above 245 MUm: singlets replaced the dominance of long chain
      formations. These observations were valid for cells acclimated to halogen light.
      Under fluorescent light, cells were more resistant to modifications in chain
      length after H2 O2 exposure. Growth along 9 h in the presence of extracellular H2
      O2 followed an hormesis response in both light regimes. Under halogen light
      conditions, alterations in chain formation and net growth were related to culture
      time, inocula concentration and geomagnetic activity (GMA) in the proceeding
      hours. Below a 16 nT threshold in GMA average growth was 0%, while above 16 nT it
      was circa +9%, independently if the local static magnetic field was altered by a
      permanent magnet or not. Mycosporine-like amino acids that can have an
      antioxidant role and are easily oxidized decreased from 7.1 to 6.5 pg cell-1 (P <
      0.05) under halogen light and exposure to 245 MUm H2 O2 . GMA, as well as UV-A,
      increased stress responsiveness that can momentarily protect cells from
      extracellular H2 O2 addition. However, stress response is dependent on bio
      availability of several micronutrients and macronutrients, many found at limiting
      concentrations in oceanic waters.

PMID- 28763100
TI  - Fungal-derived cues promote ocular autoimmunity through a Dectin-2/Card9-mediated
      mechanism.
AB  - Uveitis (intraocular inflammation) is a leading cause of loss of vision. Although
      its aetiology is largely speculative, it is thought to arise from complex genetic
      environmental interactions that break immune tolerance to generate eye-specific
      autoreactive T cells. Experimental autoimmune uveitis (EAU), induced by
      immunization with the ocular antigen, interphotoreceptor retinoid binding protein
      (IRBP), in combination with mycobacteria-containing complete Freund's adjuvant
      (CFA), has many clinical and histopathological features of human posterior
      uveitis. Studies in EAU have focused on defining pathogenic CD4+ T cell effector
      responses, such as those of T helper type 17 (Th17) cells, but the innate
      receptor pathways precipitating development of autoreactive, eye-specific T cells
      remain poorly defined. In this study, we found that fungal-derived antigens
      possess autoimmune uveitis-promoting function akin to CFA in conventional EAU.
      The capacity of commensal fungi such as Candida albicans or Saccharomyces
      cerevisae to promote IRBP-triggered EAU was mediated by Card9. Because Card9 is
      an essential signalling molecule of a subgroup of C-type lectin receptors (CLRs)
      important in host defence, we evaluated further the proximal Card9-activating
      CLRs. Using single receptor-deficient mice we identified Dectin-2, but not Mincle
      or Dectin-1, as a predominant mediator of fungal-promoted uveitis. Conversely,
      Dectin-2 activation by alpha-mannan reproduced the uveitic phenotype of EAU
      sufficiently, in a process mediated by the Card9-coupled signalling axis and
      interleukin (IL)-17 production. Taken together, this report relates the potential
      of the Dectin-2/Card9-coupled pathway in ocular autoimmunity. Not only does it
      contribute to understanding of how innate immune receptors orchestrate T cell
      mediated autoimmunity, it also reveals a previously unappreciated ability of
      fungal-derived signals to promote autoimmunity.

PMID- 28763101
TI  - Relevant genetic polymorphisms and kidney expression of Toll-like receptor (TLR)
      5 and TLR-9 in lupus nephritis.
AB  - Toll-like receptor (TLR) genetic polymorphisms may modify their expression
      causing inflammatory disorders and influencing both susceptibility and severity
      of lupus erythematosus. We aim to determine whether TLR-5 and TLR-9 gene
      polymorphisms are implicated in the susceptibility to systemic lupus
      erythematosus (SLE) and lupus nephritis (LN) and to evaluate their expressions
      and distributions in renal LN patients' biopsies. The frequencies of two SNP in
      the TLR-9 gene and one in the TLR-5 gene was examined in 106 SLE patients (among
      them 37 LN patients) and in 200 matched controls by polymerase chain reaction
      restriction fragment-length polymorphisms (PCR-RFLP) analysis. TLR-9 and TLR-5
      expressions were assessed by reverse transcription (RT)-PCR and
      immunohistochemistry carried on LN renal biopsies compared to healthy renal
      tissue. A significant genotypic and allelic association was revealed between TLR
      9-rs352140 and both SLE and LN (P < 0.05). The TLR-9 transcript level was
      significantly higher in LN biopsies compared to control (P < 0.05). This increase
      was observed histochemically in the tubulointerstitial compartment. TLR-9 was
      detectable in LN glomeruli patients but not in normal control glomeruli. No
      allelic nor genotype association was found with TLR-5-rs5744168 in SLE. but the T
      allele and the TT genotype were raised significantly in the LN group (P < 0.05).
      A significant increase in TLR-5 gene expression in LN biopsies, which contrasted
      with normal kidneys (P < 0.05), was confirmed by an intense and diffuse staining
      for TLR-5 only in LN tubules (P < 0.05). Our data show that TLR-5 and TLR-9 are
      susceptible genes to LN and that their expression is dysregulated in LN patients'
      kidneys, supporting a role of these mediators in the pathogenesis of LN.

PMID- 28763103
TI  - The lack of analgesic use (oligoanalgesia) in small animal practice.
AB  - Oligoanalgesia is defined as failure to provide analgesia in patients with acute
      pain. Treatment of pain in emergencies, critical care and perioperatively may
      influence patient outcomes: the harmful practice of withholding analgesics occurs
      in teaching hospitals and private practices and results in severe physiological
      consequences. This article discusses the prevalence, primary causes, species and
      regional differences and ways to avoid oligoanalgesia in small animal practice.
      Oligoanalgesia may be addressed by improving education on pain management in the
      veterinary curriculum, providing continuing education to veterinarians and
      implementing pain scales.

PMID- 28763105
TI  - Physiological Doses of Red Light Induce IL-4 Release in Cocultures between Human
      Keratinocytes and Immune Cells.
AB  - Phototherapy is routinely used for the treatment of various skin conditions and
      targeted therapy of superficial cancers. However, the molecular mechanisms behind
      their biological effects and the need for efficacy enhancing photosensitizers are
      not well addressed. Particularly, not much is known about the inherent effect of
      light from the visible spectrum on cytokine release and its downstream effects in
      keratinocytes and immune cells located in skin and therefore exposed to light. To
      address this, we delivered calibrated doses of well-defined light qualities (380
      to 660 nm) to cocultures of human keratinocytes and macrophage/dendritic cells in
      the absence or presence of the commonly used photosensitizer 8-methoxypsoralen (8
      MOP). The experiments identified IL-4 as a key effector cytokine released by this
      coculture model with need for 8-MOP in the UVA1 /blue (380 nm) and no requirement
      for photosensitizer in the red light spectrum (627 nm). 3D organotypic skin
      cultures treated with IL-4 showed thickening of the epidermal layer and delayed
      differentiation. However unlike IL-4 and UVA1 /blue light treatment, red light
      did not reduce the expression of keratinocyte differentiation markers or increase
      signs of photo-oxidative damage. This supports the application of isolated red
      light as a possible alternative for photo-immunotherapy without need for
      additional photosensitizers.

PMID- 28763104
TI  - LED Phototherapy with Gelatin Sponge Promotes Wound Healing in Mice.
AB  - Tiny but highly efficient, a light-emitting diode (LED) can power a therapy
      device, such as a phototherapy device, and, at the same time, decrease the
      device's size requirements. In this study, a LED phototherapy device was designed
      to investigate the possible impact on wound healing using a mouse model and a
      cell line exposed to red and blue light. To enhance wound phototherapy, a gelatin
      sponge was fabricated. Results showed that the red and blue lights promoted cell
      growth and wound healing, while the blue light with a gelatin sponge protected
      the wound from infection in the early stages of wound healing. The LED
      phototherapy device combined with the gelatin sponge, therefore, has potential
      significance in clinical application for wound healing.

PMID- 28763107
TI  - Membership analysis of the American Society of Primatologists through 2015 and
      planning for future.

PMID- 28763106
TI  - Identification of proteome, antigen protein and antigen membrane protein from
      Spiroplasma eriocheiris.
AB  - : Spiroplasma eriocheiris, which causes tremor disease in Chinese mitten crab
      Eriocheir sinensis, has led to huge economic losses in aquaculture.
      Immunoproteomics, a new scientific technique combining proteomics and
      immunological analytical methods, provided the direction of our research on S.
      eriocheiris. The aim of our study was to identify the proteome, antigen proteins
      and antigen membrane proteins of S. eriocheiris. A total of 780 S. eriocheiris
      proteins were identified by the LC-MS/MS technique. Based on immunoproteomics, 51
      proteins and 7 proteins in S. eriocheiris were identified by anti-S. eriocheiris
      serum and negative serum respectively (six proteins in common). Thus, 45
      antigenic proteins in S. eriocheiris were identified; among them, molecular
      chaperone DnaK, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ATP synthase
      subunit beta and enolase can be considered as immunogenic proteins. Similarly, 32
      membrane proteins and 6 membrane proteins were identified by anti-S. eriocheiris
      serum and negative serum respectively (two proteins in common). Thus, 30
      antigenic membrane proteins in S. eriocheiris were identified; three of them have
      been reported as surface proteins including pyruvate kinase, enolase and GAPDH.
      All of these proteins may play key roles in the pathogeny and can be used in the
      future for diagnoses and prevention. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Spiroplasma eriocheiris is a novel pathogen causing the tremor disease in Chinese
      mitten crab Eriocheir sinensis. This is the first time LC-MS/MS was used to
      identify the proteome, antigen protein and antigen membrane protein of S.
      eriocheiris. The results can certainly provide valuable information towards the
      identification of virulent proteins or diagnosis of pathogenic mechanisms.

PMID- 28763108
TI  - Biodegradation of anthracene by a newly isolated bacterial strain, Bacillus
      thuringiensis AT.ISM.1, isolated from a fly ash deposition site.
AB  - : The current study is aimed to evaluate the mechanism of anthracene degradation
      by a bacterial strain isolated from fly ash deposition site near Jamadoba Coal
      Preparation Plant, Jharkhand, India. The Bushnell-Haas media cultured (containing
      anthracene as sole carbon source) bacterial isolate was identified by 16S rRNA
      gene sequence coding as the Bacillus thuringiensis strain, which showed the
      efficiency to degrade anthracene. The degradation efficiency of the strain has
      been estimated to be around 91% (for 40 mg l-1 of anthracene concentration) after
      2 weeks of incubation at 33-36 degrees C and initial pH of 6.8-7. The growth
      kinetics of the isolated strain has been described well by the Haldane-Andrews
      model of microbial growth pattern for inhibitory substrate, with a correlation
      factor (R2 value) of 0.9790. The maximum specific growth rate (MUmax ) was
      0.01053 h-1 and the value of inhibition coefficient for Haldane model was
      specified as 18.2448 mg l-1 . In the present study, some diphenol metabolites
      were identified besides the known possible biodegradation products. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Polycyclic aromatic hydrocarbons (PAHs) are recognized
      as significant health risks and consequently listed as priority pollutants by
      environmental protection agencies across the globe. The aim of the present study
      was to degrade one of the important PAHs, anthracene, by a newly isolated
      Bacillus thuringiensis strain. This is the first report of anthracene degradation
      by B. thuringiensis. This is also the very first growth kinetic study of a
      bacteria in an anthracene-containing medium. Some diphenol metabolites were found
      for the first time as anthracene biodegradation by-products, which can be an
      indication towards a new pathway.

PMID- 28763109
TI  - Synthesis of 14 C- and 2 H-labelled CHF6001: A new potent PDE4 inhibitor.
AB  - An 8-step preparation of 14 C-labelled CHF6001, a potent phosphodiesterase 4
      inhibitor in the treatment of respiratory diseases, is described. An overall
      yield of approximately 9% was obtained starting from copper[14 C]cyanide. The
      synthesis of a stable labelled version of CHF6001 is also reported using the
      commercially available trideuterated bromomethylcyclopropane as starting
      material.

PMID- 28763110
TI  - Co-expression of lipase isozymes for enhanced expression in Pichia pastoris.
AB  - : To enhance the overall expression level of lipase isozymes which catalyse the
      same reaction in Pichia pastoris through co-expression of isozymes from different
      sources; several types of co-expression ways were constructed to determine the co
      expression efficiencies of lipase isozymes in P. pastoris. The results showed
      that the Kex2-mediated co-expression of lipase isozymes could express Rhizomucor
      miehei lipase (RML) and Thermomyces lanuginosus lipase (TLL) simultaneously, and
      GS-RMk-kTL displayed an average lipase activity of 306.91 U ml-1 , higher than GS
      RML and GS-kTL (2.89 and 300.59 U ml-1 ) expressed independently in P. pastoris,
      and the sum of both (303.48 U ml-1 ), implying the potential of isozyme co
      expression mediated by Kex2 in increasing the overall recombinant expression, but
      the low recombinant expression of RML in P. pastoris weakened the overall
      increasing effect on lipase expression in the isozyme co-expression strains. In
      addition, the fusion isozymes were successfully expressed, but with low lipase
      activities. Furthermore, 2A peptide could successfully mediate the co-expression
      and secretion of lipase isozymes, but it seriously affected the expression of TLL
      downstream of 2A peptide. SIGNIFICANCE AND IMPACT OF THE STUDY: The low
      production level is one of the limitation factors for decreasing the prices of
      enzymes and expanding their application in industry as the biocatalysts. This
      research focuses on developing lipase isozyme co-expression strategies in Pichia
      pastoris to enhance the expression level of overall lipase isozymes which
      catalyse the same reaction. The Kex2-mediated co-expression strategy of lipase
      isozymes could potentially enhance the overall isozyme expression, and isozyme co
      expression might provide a new direction for improving the recombinant isozyme
      expression, and decreasing the production and application prices of these mixed
      enzymes as biocatalysts.

PMID- 28763111
TI  - Left-Corner Parsing With Distributed Associative Memory Produces Surprisal and
      Locality Effects.
AB  - This article describes a left-corner parser implemented within a cognitively and
      neurologically motivated distributed model of memory. This parser's approach to
      syntactic ambiguity points toward a tidy account both of surprisal effects and of
      locality effects, such as the parsing breakdowns caused by center embedding. The
      model provides an algorithmic-level (Marr, 1982) account of these breakdowns: The
      structure of the parser's memory and the nature of incremental parsing produce a
      smooth degradation of processing accuracy for longer center embeddings, and a
      steeper degradation when they are nested, in line with recall observations by
      Miller and Isard (1964) and speed-accuracy trade-off observations by McElree et
      al. (2003). Modeling results show that this effect is distinct from the effects
      of ambiguity and exceeds the effect of mere sentence length.

PMID- 28763112
TI  - Systematic literature review of clinical trials evaluating pharmacotherapy for
      overactive bladder in elderly patients: An assessment of trial quality.
AB  - AIMS: Overactive bladder (OAB) disproportionately affects older-aged adults, yet
      most randomized controlled trials (RCTs) underrepresent patients >=65. This
      systematic literature review (SLR) identified RCTs evaluating beta-3 adrenergic
      agonists or muscarinic antagonists in elderly patients with OAB, and compared
      study quality across trials. METHODS: MEDLINE(r) , Embase(r) , and Cochrane
      Collaboration Central Register of Clinical Trials databases were searched from
      inception through April 28, 2015 to identify published, peer-reviewed RCT reports
      evaluating beta-3 adrenergic agonists or muscarinic antagonists in elderly OAB
      patients (either >=65 years or study-described as "elderly"). To assess study
      quality of RCT reports, we focused on internal/external validity, assessed via
      two scales: the validated Effective Public Health Practice Project [EPHPP]):
      Quality Assessment Tool for Quantitative Studies, and a tool commissioned by the
      Agency for Healthcare Research and Quality (AHRQ). RESULTS: Database searches
      yielded 1380 records that were then screened according to predefined
      inclusion/exclusion criteria. We included eight papers meeting study criteria.
      Despite scientific community efforts to improve RCT reporting standards,
      published reports still include incomplete and inconsistent reporting-of subject
      attrition, baseline patient characteristics, inclusion/exclusion criteria, and
      other important details. Only three of the eight OAB RCTs in this review received
      quality ratings of Strong (EPHPP) or Fair (AHRQ) and were multicenter with large
      samples. CONCLUSIONS: Despite the prevalence of OAB among older age individuals,
      relatively few RCTs evaluate OAB treatments explicitly among elderly subjects.
      The findings from this quality assessment suggest some areas for improvement in
      both conduct and reporting of future RCTs assessing OAB treatment in elderly.

PMID- 28763113
TI  - Distribution of cardiac troponin I in the Japanese general population and factors
      influencing its concentrations.
AB  - BACKGROUND: The 99th percentile of cardiac troponin I level in the general
      population is accepted as the cut-off for the diagnosis of acute myocardial
      infarction (AMI). However, it is not clear whether the cut-offs derived in
      racially and geographically different populations are applicable in Japan.
      METHODS: Troponin I was determined using the Abbott ARCHITECT STAT high-sensitive
      troponin I immunoassay in 698 apparently healthy individuals who visited the
      Japanese Red Cross Medical Center for a health checkup. RESULTS: The 99th
      percentile of the hsTnI in the overall population was 22.5 (95% confidence
      interval (CI), 16.8-36.6) pg/mL, 17.7 (95% CI 12.0-22.8) pg/mL for females and
      30.6 (95% CI 17.1-53.4) pg/mL for males. The median of the hsTnI in the overall
      population was 3.2 (95% CI, 3.0-3.3) pg/mL, 2.6 (95% CI 2.4-2.8) pg/mL for
      females and 4.0 (95% CI 3.8-4.3) pg/mL for males. The age and gender had a
      significant influence on these values. The troponin I level also showed
      significant associations with the body mass index (BMI), the gamma glutamyl
      transferase (GGT), lactate dehydrogenase (LDH), estimated glomerular filtration
      rate (eGFR), and cardiac abnormalities by electrocardiography (ECG) but not with
      the high-sensitive C-reactive protein (hsCRP) level. CONCLUSIONS: The 99th
      percentiles of the troponin I measured in the general population in Japan were
      comparable as the ones derived in the US, Germany, and Singapore. The troponin I
      level was dependent on the gender, age, BMI, and cardiac abnormalities found by
      ECG but not by the hsCRP level.

PMID- 28763114
TI  - Assimilation efficiency of sediment-bound PCBs ingested by fish impacted by
      strong sorption.
AB  - Uptake of polychlorinated biphenyls (PCBs) by fish is controlled by the
      bioavailability of ingested PCBs in the gut and the freely dissolved
      concentration in the water moving across the gills. The prediction of
      bioaccumulation in fish relies on models that account for these exposure routes;
      however, these models typically do not account for incidental ingestion of
      sediment by fish, which is not well studied. The literature values for the PCB
      assimilation efficiency in the gut have been reported for compounds in food
      matrices and not associated with sediment particles. It is also unclear how
      mitigation strategies that alter PCB bioavailability in sediments affect
      predictions made by the bioaccumulation models when sediment ingestion is
      involved. To test the bioavailability of PCBs from treated and untreated
      sediments, dietary assimilation efficiencies were measured for 16 PCB congeners
      in mummichogs (Fundulus heteroclitus) that were fed 4 experimental diets. Diets
      consisted of PCB-spiked earthworms, spiked untreated sediment mixed with
      earthworms, spiked activated carbon-treated sediment mixed with earthworms, and
      spiked activated carbon mixed with earthworms. Assimilation efficiencies were
      determined by calculating the ratio of PCB mass in the fish tissue to the PCB
      mass in the food after a pulse feeding experiment. Assimilation efficiencies of
      PCBs associated with earthworm diet were similar to the values reported in the
      literature. Fish that were fed the PCB-spiked untreated sediment and activated
      carbon particles exhibited the highest and lowest assimilation efficiencies,
      respectively, over a wide KOW range. Assimilation efficiencies of sediment-bound
      PCBs were significantly reduced (31-93% reduction for different congeners) after
      amendment with activated carbon. The present study indicates that assimilation of
      PCBs can be reduced by sorption to black carbon. Environ Toxicol Chem
      2017;36:3480-3488. (c) 2017 SETAC.

PMID- 28763115
TI  - Design, Synthesis, and the Biological Evaluation of a New Series of Acyclic 1,2,3
      Triazole Nucleosides.
AB  - A new strategy for the synthesis of N3 -benzoylated- and N3 -benzylated N1 
      propargylquinazoline-2,4-diones 30a-d and 31a-d from isatoic anhydride 41 is
      reported. The alkynes 30a-d and 31a-d were applied in the 1,3-dipolar
      cycloadditions with azides 27 and 28 to synthesize acyclic 1,2,3-triazole
      nucleosides. The obtained alkynes and 1,2,3-triazole were evaluated for antiviral
      activity against a broad range of DNA and RNA viruses. The alkyne 30d showed
      activity against adenovirus-2 (EC50  = 8.3 MUM), while compounds 37a and 37d were
      also active toward herpes simplex virus-1 wild-type and thymidine kinase
      deficient (HSV-1 TK- ) strains (EC50 values in the range of 4.6-13.8 MUM). In
      addition, compounds 30a, 30b, 37b, and 37c exhibited activity toward varicella
      zoster virus (VZV) TK+ and TK- strains (EC50  = 2.1-9.5 MUM). The compound 30b
      proved to be the most selective against VZV and displayed marginal activity
      against human cytomegalovirus (HCMV). Although the compound 30a had improved anti
      HCMV activity, the increase in anti-HCMV activity was accompanied by significant
      toxicity. Compounds 37a and 37d showed inhibitory effects toward the human T
      lymphocyte (CEM) cell line (IC50  = 21 +/- 7 and 22 +/- 1 MUM, respectively),
      while compound 35 exhibited cytostatic activity toward HMEC-1 cells (IC50  = 28
      +/- 2 MUM).

PMID- 28763116
TI  - Urodynamic characteristics of pelvic lipomatosis with glandular cystitis patients
      correlate with morphologic alterations of the urinary system and disease
      severity.
AB  - AIMS: To explore urodynamic characteristics and their clinical value in pelvic
      lipomatosis (PL) patients. METHODS: We reviewed the clinical information of 84 PL
      patients. A voiding pressure-flow study was used to classify patients into
      nonoutlet obstruction (NOO), latter-half-section obstruction (LHSO), or whole
      section bladder outlet obstruction (BOO) groups. Urinary morphologic features
      were measured by imaging examination and cystoscopy. RESULTS: A unique LHSO that
      presented as sudden increasing detrusor pressure (Pdet) and decreasing flow rate
      in the latter half of voiding was observed for 52.4% (44 of 84) patients.
      Overall, 27.4% (23 of 84 patients) were diagnosed with BOO with whole-section
      increasing Pdet and decreasing flow rate. According to the morphologic feature
      analyses, the NOO patients had the largest angle of anteroposterior vesical walls
      (P < 0.001) and the least severe thickened bladder trigone (P = 0.015). The
      external compression at the bladder neck and thickened bladder trigone caused a
      prolonged and strictured bladder outlet tract (see the Supplementary video).
      There were 0, 5, and 4 urinary diversions performed in the NOO, LHSO, and BOO
      groups at diagnosis (P = 0.055). No patients in the NOO group, seven in the LHSO
      group, and two patients in the BOO group had disease progression at follow-up.
      Two LHSO patients and one BOO patients without hydronephrosis at diagnosis
      developed to hydronephrosis during follow-up. CONCLUSIONS: Morphologic
      alterations of the urinary system of PL patients lead to unique LHSO or BOO on
      UDS. The presences of LHSO and BOO are associated with disease severity and
      progression.

PMID- 28763117
TI  - Foetal growth restriction is associated with poor reading and spelling skills at
      eight years to 10 years of age.
AB  - AIM: Foetal growth restriction (FGR) is associated with communication problems,
      which might lead to poor literacy skills. The reading and spelling skills of
      eight- to 10-year-old FGR children born at 24-40 gestational weeks were compared
      with those of their gestational age-matched, appropriately grown (AGA) peers.
      METHODS: A prospectively collected cohort of 37 FGR and 31 AGA children was
      recruited prenatally at a Finnish tertiary care centre during 1998-2001. The
      children's reading and spelling skills were assessed using standardised tests for
      Finnish-speaking second and third graders. RESULTS: Significantly more children
      performed below the 10th percentile normal values for reading and spelling skills
      in the FGR group than in the AGA group. At nine years of age, the FGR children
      had significantly poorer performance in word reading skills and reading fluency,
      reading accuracy and reading comprehension than the AGA controls. No between
      group differences were detected at eight years of age. CONCLUSION: FGR is
      associated with poor performance in reading and spelling skills. A third of the
      FGR children performed below the 10th percentile normal values at nine years of
      age. These results indicate a need to continuously evaluate linguistic and
      literacy skills as FGR children age to ensure optimal support.

PMID- 28763118
TI  - Mechanical stimulation of mesenchymal stem cells: Implications for cartilage
      tissue engineering.
AB  - Articular cartilage is a load-bearing tissue playing a crucial mechanical role in
      diarthrodial joints, facilitating joint articulation, and minimizing wear. The
      significance of biomechanical stimuli in the development of cartilage and
      maintenance of chondrocyte phenotype in adult tissues has been well documented.
      Furthermore, dysregulated loading is associated with cartilage pathology
      highlighting the importance of mechanical cues in cartilage homeostasis. The
      repair of damaged articular cartilage resulting from trauma or degenerative joint
      disease poses a major challenge due to a low intrinsic capacity of cartilage for
      self-renewal, attributable to its avascular nature. Bone marrow-derived
      mesenchymal stem cells (MSCs) are considered a promising cell type for cartilage
      replacement strategies due to their chondrogenic differentiation potential.
      Chondrogenesis of MSCs is influenced not only by biological factors but also by
      the environment itself, and various efforts to date have focused on harnessing
      biomechanics to enhance chondrogenic differentiation of MSCs. Furthermore,
      recapitulating mechanical cues associated with cartilage development and
      homeostasis in vivo, may facilitate the development of a cellular phenotype
      resembling native articular cartilage. The goal of this review is to summarize
      current literature examining the effect of mechanical cues on cartilage
      homeostasis, disease, and MSC chondrogenesis. The role of biological factors
      produced by MSCs in response to mechanical loading will also be examined. An in
      depth understanding of the impact of mechanical stimulation on the chondrogenic
      differentiation of MSCs in terms of endogenous bioactive factor production and
      signaling pathways involved, may identify therapeutic targets and facilitate the
      development of more robust strategies for cartilage replacement using MSCs. (c)
      2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
      Res 36:52-63, 2018.

PMID- 28763120
TI  - Synthesis of Terminal Ethynyl Aryl Selenides and Sulfides Based on the Retro
      Favorskii Reaction of Hydroxypropargyl Precursors.
AB  - The retro-Favorskii reaction is an excellent way to achieve terminal alkynes.
      Methodologies that connect the synthesis of terminal alkynes and organochalcogen
      motifs are important for the construction of novel compounds. Fourteen new
      terminal alkynes containing either Csp -S or Csp -Se bonds were selectively
      prepared through the retro-Favorskii reaction from the respective carbinol
      precursors. It was discovered that terminal chalcogen alkynes were stable for
      weeks if stored as a solution in hexanes.

PMID- 28763119
TI  - The prevalence and molecular characterization of (deltabeta)0 -thalassemia and
      hereditary persistence of fetal hemoglobin in the Chinese Zhuang population.
AB  - OBJECTIVE: To reveal the prevalence and molecular characterization of
      (deltabeta)0 -thalassemia [(deltabeta)0 -thal] and hereditary persistence of
      fetal hemoglobin (HPFH) in the Chinese Zhuang population. METHODS: A total of 105
      subjects with fetal hemoglobin (Hb F) level >=5% from 14 204 unrelated ones were
      selected for the study. Multiplex ligation dependent probe amplification was
      firstly used to analyze dosage changes of the beta-globin gene cluster for
      associated with (deltabeta)0 -thal and HPFH mutations. The gap polymerase chain
      reaction was then performed to identify the deletions using the respective
      flanking primers. Hematologic data were recorded and correlated with the
      molecular findings. RESULTS: Twenty-one (0.15%) subjects were diagnosed with
      Chinese G gamma(A gammadeltabeta)0 -thal. Nine (0.06%) were diagnosed with
      Southeast Asia HPFH (SEA-HPFH) deletion. Seventy-five (0.53%) cases remained
      uncharacterized. Three genotypes for Chinese G gamma(A gammadeltabeta)0 -thal and
      SEA-HPFH deletion were identified, respectively. The genotype-phenotype
      relationships were discussed. CONCLUSION: Our study for the first time
      demonstrated that (deltabeta)0 and HPFH were not rare events, and molecular
      characterized G gamma(A gammadeltabeta)0 -thal and HFPH mutations in the Chinese
      Zhuang population. The findings in our study will be useful in genetic counseling
      and prenatal diagnostic service of beta-thalassemia in this populations.

PMID- 28763121
TI  - Proportion of daily capillary blood glucose readings required in the target range
      for target glycaemic control: shift of focus from target range to proportion in
      range.
AB  - AIM: Most guidelines provide people with Type 1 diabetes with pre- and post-meal
      capillary blood glucose (CBG) targets to achieve optimal glycaemic control. We
      evaluated the proportion of daily CBG readings between 4 and 10 mmol/l in people
      achieving different HbA1c levels. METHOD: We analysed CBG data from routine
      pump/meter downloads from 201 adults treated with continuous subcutaneous insulin
      infusion (CSII) at a single hospital clinic. Exclusion criteria were CSII < 6
      months, < 3 CBG/day, pregnancy, haemoglobinopathy and continuous sensor use.
      People were categorized into three groups based on HbA1c : < 58 mmol/mol, < 7.5%
      (n = 58); 58-74 mmol/mol, 7.5-8.9% (n = 107); and >= 75 mmol/mol, >= 9.0% (n =
      36). RESULTS: Participants had a mean age of 43 +/- 13 years and mean HBA1c of 64
      mmol/mol (8.0 +/- 1.1%). 47% of people started CSII for raised HbA1c , 25% due to
      hypoglycaemia and the rest during pregnancy. Downloads contained a mean of 22 +/-
      6.8 days of data per participant. CBG frequency was similar between the three
      groups (5.6 +/- 2.0, 5.6 +/- 1.9 and 5.4 +/- 1.2 CBG/day; P = 0.468). The
      proportion of CBG readings between 4 and 10 mmol/l (72-180 mg/dl) was 57.3 +/-
      25.4%, 50.6 +/- 11.1% and 39.9 +/- 16.5% (P < 0.0001); < 4 mmol was 13.8%, 8.8%
      and 4.4% (P < 0.0001) and > 10 mmol/l was 28.9 +/- 16.5%, 40.6 +/- 12.1% and 55.6
      +/- 17.9% (P < 0.0001) in the three groups respectively. CONCLUSIONS:
      Participants achieving HBA1c < 58 mmol/mol (< 7.5%) had ~ 60% of CBG readings in
      range (4-10 mmol/l), with up to 30% of readings > 10 mmol/l. This target of
      achieving 60% or more readings within target, and being permissive with up to 30%
      readings > 10 mmol/l may be a novel target for people with diabetes, and may
      reduce anxiety associated with readings out of range.

PMID- 28763122
TI  - Experimental and Theoretical Investigation of the Light-Driven Hydrogen Evolution
      by Polyoxometalate-Photosensitizer Dyads.
AB  - The visible-light-driven hydrogen evolution reaction (HER) by covalent
      photosensitizer-catalyst dyads is one of the most elegant concepts in
      supramolecular homogeneous solar energy conversion. The intricacies of catalyst
      reactivity and photosensitizer-catalyst interactions require a detailed
      fundamental understanding of the system to rationalize the observed reactivities.
      Here, we report three dyads based on the covalent imine-bond linkage of an
      iridium photosensitizer and an organo-functionalized Anderson polyoxometalate
      anion [MMo6 O18 {(OCH2 )3 CNH2 }2 ]3- (M=Mn3+ , Fe3+ , Co3+ ). Modification of
      the central metal ion M is used to modulate the HER activity. Detailed
      theoretical and experimental studies examine the role of the central metal ion M
      and provide critical understanding of the redox activity and light-driven HER
      activity of the novel dyads. Thus, the study enables a knowledge-based
      optimization of HER dyads by chemical modification of the reactive metal oxide
      components.

PMID- 28763124
TI  - Anti-Electrostatic CH-Ion Bonding in Decorated Graphanes.
AB  - State-of-the-art computations combined with Ziegler-Rauk energy decomposition
      analyses are employed to introduce a new class of anti-electrostatic ion-sigma
      bonds with considerable stability and a substantial contribution from charge
      transfer and dispersion between ions and finite-size functionalized graphane
      flakes, G-XYs. G-XYs have diverse electric multipolar moments that are comparable
      with those of newly synthesized all-cis-hexa-halocyclohexanes. The strong, long
      range electrostatic and Pauli repulsions between some G-XYs and certain ions
      induce a gas-phase energy barrier to the physisorption of ions on the surface of
      G-XYs. However, the repulsive interactions can be overbalanced by the strong
      orbital interactions operating in the formation of ion-sigma complexes at short
      range, leading to covalent-type intermolecular bonds as strong as -34 kcal mol-1
      .

PMID- 28763125
TI  - Small-Molecule-Induced Soluble Oligomers of alpha-Synuclein with Helical
      Structure.
AB  - Accumulation of alpha-synuclein (alphaSyn) aggregates constitutes the hallmark of
      synucleinopathies including Parkinson's disease. However, many steps from the
      innocuous, monomeric alphaSyn toward misfolded oligomers and fibrillar species
      remain unclear. Here, we show that alphaSyn can form in solution alpha-helical
      oligomers, which are off-pathway to fibrillization, through interaction with the
      tetrapyrrole phthalocyanine tetrasulfonate. Chemical cross-linking combined with
      mass spectrometry reveals a large number of intermolecular cross-links along the
      entire alphaSyn sequence in the phthalocyanine tetrasulfonate-stabilized alphaSyn
      oligomers. Our study suggests that stabilization of structured oligomers by small
      molecules provides a viable strategy to interfere with alphaSyn fibrillization.

PMID- 28763123
TI  - Laying Waste to Mercury: Inexpensive Sorbents Made from Sulfur and Recycled
      Cooking Oils.
AB  - Mercury pollution threatens the environment and human health across the globe.
      This neurotoxic substance is encountered in artisanal gold mining, coal
      combustion, oil and gas refining, waste incineration, chloralkali plant
      operation, metallurgy, and areas of agriculture in which mercury-rich fungicides
      are used. Thousands of tonnes of mercury are emitted annually through these
      activities. With the Minamata Convention on Mercury entering force this year,
      increasing regulation of mercury pollution is imminent. It is therefore critical
      to provide inexpensive and scalable mercury sorbents. The research herein
      addresses this need by introducing low-cost mercury sorbents made solely from
      sulfur and unsaturated cooking oils. A porous version of the polymer was prepared
      by simply synthesising the polymer in the presence of a sodium chloride porogen.
      The resulting material is a rubber that captures liquid mercury metal, mercury
      vapour, inorganic mercury bound to organic matter, and highly toxic alkylmercury
      compounds. Mercury removal from air, water and soil was demonstrated. Because
      sulfur is a by-product of petroleum refining and spent cooking oils from the food
      industry are suitable starting materials, these mercury-capturing polymers can be
      synthesised entirely from waste and supplied on multi-kilogram scales. This study
      is therefore an advance in waste valorisation and environmental chemistry.

PMID- 28763126
TI  - Porphyrins Conjugated with Peripheral Thiolato Gold(I) Complexes for Enhanced
      Photodynamic Therapy.
AB  - Porphyrins fused to imidazolium salts across two neighboring beta-pyrrolic
      positions were used as N-heterocyclic carbene (NHC) precursors to anchor AuI -Cl
      complexes at their periphery. Synthesis of several thiolato-AuI complexes was
      then achieved by substituting chloride for thiolates. Photodynamic properties of
      these complexes were investigated: the data obtained show that the Au-S bonds
      could be cleaved upon irradiation. The proposed mechanism to explain the release
      of thiolate moiety involves the S atom oxidation by singlet oxygen generated in
      the course of irradiation. In view of photodynamic therapy (PDT) applications,
      these porphyrins fused to NHC-AuI complexes were tested as photosensitizers to
      kill MCF-7 breast cancer cells. Results show the important role played by the
      ancillary ligands (chloride versus thiolates) on the photodynamic effect.

PMID- 28763128
TI  - Chemical Tagging with tert-Butyl and Trimethylsilyl Groups for Measuring
      Intermolecular Nuclear Overhauser Effects in a Large Protein-Ligand Complex.
AB  - Intermolecular 1 H-1 H nuclear Overhauser effects (NOE) present a powerful tool
      to assess contacts between proteins and binding partners, but are difficult to
      identify for complexes of high molecular weight. This report shows that
      intermolecular NOEs can readily be observed following chemical labeling with tert
      butyl or trimethylsilyl (TMS) groups. Proteins can be furnished with tert-butyl
      or TMS groups site-specifically using genetically encoded unnatural amino acids
      or by chemical modification of single cysteine residues. No isotope labeling is
      required. The approach is demonstrated with the 95 kDa complex between tetrameric
      E. coli single-stranded DNA binding protein (SSB) and single-stranded DNA.

PMID- 28763127
TI  - European Veterinary Renal Pathology Service: A Survey Over a 7-Year Period (2008
      2015).
AB  - BACKGROUND: The European Veterinary Renal Pathology Service (EVRPS) is the first
      Web-based registry for canine renal biopsy specimens in Europe.
      HYPOTHESIS/OBJECTIVES: The aim was to verify whether differences exist between
      the clinical and laboratory presentation of dogs with nephropathy according to
      renal pathological findings, as defined by light and electron microscopy of renal
      biopsy specimens submitted to EVRPS. ANIMALS: Renal biopsy specimens of dogs were
      collected from the archive of the service (n = 254). Cases were included if both
      light and electron microscopy were available (n = 162). METHODS: Renal biopsy
      specimens were classified based on the morphological diagnoses. Thereafter, they
      were grouped into 3 disease categories, including immune-complex-mediated
      glomerulonephritis (ICGN), non-immune-complex-mediated GN (non-ICGN), and renal
      lesions not otherwise specified (RL-NOS). Differences among morphological
      diagnoses and among disease categories were investigated for clinical and
      laboratory variables. RESULTS: Serum albumin concentration was lower in dogs with
      ICGN than in those with non-ICGN (P = 0.006) or RL-NOS (P = 0.000), and the urine
      protein-to-creatinine ratio (UPC) was significantly higher in ICGN than in the
      other 2 disease categories. Regarding morphological diagnoses, albumin was
      significantly lower in amyloidosis (AMY) and membranous (MGN),
      membranoproliferative (MPGN) or mixed glomerulonephritis (MixGN) than in minimal
      change disease, primary (FSGS I) or secondary (FSGS II) focal and segmental
      glomerulosclerosis and juvenile nephropathies (JN). The UPC was higher in MPGN
      than in FSGS I and FSGS II. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with ICGN,
      in particular MPGN, had higher protein loss than those with non-ICGN or RL-NOS,
      leading to more severe hypoalbuminemia. Clinical and laboratory differentiation
      among dogs with the different morphological diagnoses and among dogs with
      different disease categories was difficult due to overlapping results.

PMID- 28763129
TI  - Profiling sedentary behavior in breast cancer survivors: Links with depression
      symptoms during the early survivorship period.
AB  - OBJECTIVE: Depression symptoms are prevalent among breast cancer survivors (BCS).
      Reducing sedentary behavior (SED) may be a non-pharmaceutical strategy for
      alleviating depression symptoms. However, little is known about SED among BCS.
      The present study aimed to: (i) describe SED behaviors among BCS and identify
      unique SED groups based on different SED dimensions; (ii) identify personal and
      cancer-specific factors that discriminate SED clusters; and (iii) examine the
      association between SED clusters and depression symptoms. METHODS: Baseline self
      report demographic and medical information was collected from 187 BCS. SED and
      physical activity were assessed over seven days using an accelerometer. Self
      reported depression symptoms were reported three months later. Multiple
      dimensions of SED were identified and examined in cluster analysis. The clusters
      were examined for differences using multivariate analysis of variance and chi
      square analyses. The difference in depression symptoms among SED groups was
      assessed using an analysis of covariance. RESULTS: High and low SED groups were
      identified. Survivors in the high SED cluster were significantly older, heavier,
      less physically active, reported less education, and were more likely to have
      undergone lymph/axial node dissection. Women in the high SED cluster reported
      significantly higher depression symptoms prospectively (M = 9.50, SD = 6.07)
      compared to women in the low SED group (M = 6.89, SD = 5.18), F(8,179) = 4.97, p
      = 0.03, R2  = 0.34. CONCLUSIONS: The importance of understanding multiple
      dimensions of SED among BCS was highlighted. Reducing SED during the early
      survivorship period may alleviate depression symptoms.

PMID- 28763130
TI  - A critical analysis of the utility of component tests in the diagnosis of pollen
      related peanut and hazelnut allergy in the context of the BSACI guideline.

PMID- 28763131
TI  - The effect of allergen-induced bronchoconstriction on concentration of 5-oxo-ETE
      in exhaled breath condensate of house dust mite-allergic patients.
AB  - BACKGROUND: Arachidonic acid metabolites regulate several aspects of airway
      function including inflammation, muscle contraction and mucous secretion.
      OBJECTIVE: The aim of this study was to evaluate concentration of selected 5
      lipoxygenase- and cyclooxygenase-derived eicosanoids in exhaled breath condensate
      (EBC) during allergen-induced bronchoconstriction. METHODS: The study was
      performed on 24 allergic rhinitis/asthma patients sensitized to a house dust mite
      (HDM) Dermatophagoides pteronyssinus (Dp) and 13 healthy controls (HCs).
      Bronchial challenge with Dp extract was performed only in the allergic patients.
      EBC samples were collected before (T0 ) and during Dp-induced bronchoconstriction
      (TEAR ). Eicosanoid concentration was measured using HPLC-tandem mass
      spectrometry. RESULTS: Significant bronchoconstriction after Dp challenge was
      demonstrated in 15 patients (Rs), while in 9 patients (NRs) no asthmatic response
      could be detected. At T0 the most abundant eicosanoids in EBC of HDM-allergic
      patients were LTB4 and 5-oxo-ETE, while in HCs EBC concentration of LTB4 was
      significantly greater than that of 5-oxo-ETE. Allergen challenge resulted in
      significant increase in EBC concentration of 5-oxo-ETE, LTD4 and 8-iso-PGE2 only
      in Rs. At TEAR , the relative change of 5-oxo-ETE concentration in EBC correlated
      with decrease of peripheral blood eosinophilia (R = -0.774; P = .0012). Moreover,
      the relative increase of 5-oxo-ETE in EBC at TEAR significantly correlated with
      the severity of the subsequent late asthmatic response (R = 0.683, P = .007).
      CONCLUSION: Our study demonstrates significant up-regulation of 5-oxo-ETE
      synthesis in HDM-allergic patients and indicates possible involvement of that
      mediator in the pathogenesis of allergic asthma.

PMID- 28763132
TI  - Hydrolysed ovalbumin offers more effective preventive and therapeutic protection
      against egg allergy than the intact protein.
AB  - BACKGROUND: The application of specific immunotherapy to stimulate oral tolerance
      towards food allergens is hampered by the high frequency of adverse side-effects
      and the excessive duration of the treatments. OBJECTIVE: In this work, a
      hydrolysate of ovalbumin with pepsin (OP), selected for its low IgE reactivity
      and Th2-stimulating capacity, was assayed for its ability to prevent and treat
      allergy to egg white (EW). METHODS: As a first step, the safety of OP, in terms
      of the absence of sensitizing and eliciting potential, was evaluated in BALB/c
      mice. Then, its suitability for prophylactic and therapeutic applications was
      compared with that of the intact allergen, paying attention to the molecular and
      cellular mechanisms involved in the control of the allergic process. To this aim,
      IgE, IgG1, IgG2a and IgA levels, allergic reactions, expression of genes related
      to Th1, Th2, Th17 and Treg responses, dendritic and T cell populations were
      assessed in intestinal tissues and spleens of EW-allergic mice, either untreated
      or treated with intact ovalbumin (OVA) or OP. RESULTS: The hydrolysate of OVA
      with pepsin was hypoallergenic, lacked sensitizing potential and offered
      preventive and therapeutic protection against allergy to EW through the induction
      of Treg cells and the up-regulation of TGF-beta, IL-10, IL-17, Foxp3 and
      RORgammat in intestinal tissues. This restrained the expression of GATA3 and the
      differentiation of Th2 cells, leading to low cytokine responses following ex vivo
      spleen cell stimulation. As compared with intact OVA, OP was more effective
      against sensitization. In addition, in the therapeutic setting, OP provided
      quicker desensitization that lasted for at least 3 weeks after discontinuation of
      the therapy. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides evidence for
      the superior role of hydrolysed, as compared to intact allergens, in the
      prevention of allergy development and in the promotion of long-term
      desensitization, as well as of intermolecular tolerance.

PMID- 28763133
TI  - Physical activity and exercise self-regulation in cancer survivors: A qualitative
      study.
AB  - OBJECTIVE: Despite the benefits of physical activity, many cancer survivors do
      not adhere to clinically recommended levels. This qualitative study investigated
      factors of self-regulation contributing to survivor physical activity patterns.
      METHODS: Participants attended focus groups with prompts on exercise habits and
      self-regulation on the basis of social cognitive theory, self-determination
      theory, and self-regulation theory. Content analysis with a priori codes was
      conducted to identify emergent themes. RESULTS: Participants (n = 35) were
      predominately older (63.7 y +/- 10.8), female (69%), white (71%), and breast
      cancer (60%) survivors, with 41% not meeting activity guidelines. Emergent themes
      included exercise goal development, selection, and attainment; exercise planning;
      and self-reward. Participants tended to develop values-based, general goals
      rather than action-based, measurable goals. Goal attainment success emerged as a
      facilitator of future goal performance; completing a current goal facilitated
      subsequent goal attainment, while failure hindered future goal completion. Rather
      than having deliberate intentions to schedule exercise, participants exercised if
      expedient in the context of normal daily activities. Food consumption emerged as
      a major mechanism for self-reward. CONCLUSIONS: Our findings suggest that values
      based goals, unplanned activity, influence from previous goal attempts, and self
      reward were important factors related to self-regulation. Interventions designed
      to improve self-regulation may consider facilitating development of autonomous,
      value-based goals, assisting in development of strategies for future goals if
      current goals are not met, endorsing exercise as a scheduled activity, and
      introducing healthy self-reward alternatives.

PMID- 28763134
TI  - Response of microbial community and catabolic genes to simulated petroleum
      hydrocarbon spills in soils/sediments from different geographic locations.
AB  - AIMS: Study the response of microbial communities and selected petroleum
      hydrocarbon (PH)-degrading genes on simulated PH spills in soils/sediments from
      different geographic locations. METHODS AND RESULTS: A microcosm experiment was
      conducted by spiking mixtures of petroleum hydrocarbons (PHs) to soils/sediments
      collected from four different regions of China, including the Dagang Oilfield
      (DG), Sand of Bohai Sea (SS), Northeast China (NE) and Xiamen (XM). Changes in
      bacterial community and the abundance of PH-degrading genes (alkB, nah and phe)
      were analysed by denaturing gradient electrophoresis (DGGE) and qPCR,
      respectively. Degradation of alkanes and PAHs in SS and NE materials were greater
      (P < 0.05) than those in DG and XM. Clay content was negatively correlated with
      the degradation of total alkanes by 112 days and PAHs by 56 days, while total
      organic carbon content was negatively correlated with initial degradation of
      total alkanes as well as PAHs. Abundances of alkB, nah and phe genes increased 10
      to 100-fold and varied by soil type over the incubation period. DGGE
      fingerprints identified the dominance of alpha-, beta- and gamma-Proteobacteria
      (Gram -ve) and Actinobacteria (Gram +ve) bacteria associated with degradation of
      PHs in the materials studied. CONCLUSION: The geographic divergence resulting
      from the heterogeneity of physicochemical properties of soils/sediments appeared
      to influence the abundance of metabolic genes and community structure of microbes
      capable of degrading PHs. SIGNIFICANCE AND IMPACT OF THE STUDY: When developing
      practical in-situ bioremediation approaches for PHs contamination of
      soils/sediment, appropriate microbial community structures and the abundance of
      PH-degrading genes appear to be influenced by geographic location.

PMID- 28763135
TI  - Nonlinear electrokinetic effects in insulator-based dielectrophoretic systems.
AB  - Insulator-based dielectrophoresis (iDEP) has emerged as a powerful tool for
      multiple biomicrofluidic operations, such as cell separation and concentration.
      The key feature for iDEP systems is the alteration of insulating microchannel
      geometries to create strong electric field gradients. Under AC electric fields,
      this strong electric field gradient can affect fluid flow by (at least) two
      nonlinear electrokinetic phenomena; (a) electrothermal flow due to Joule heating
      and (b) induced charge electroosmosis (ICEO) near the microchannel constrictions
      of small (but finite) permittivity and conductivity. This paper presents an
      experimental and theoretical study on the interplay of electrothermal and ICEO
      flows near microchannel constrictions with various geometries and fluid ionic
      strengths, which are crucial design factors for iDEP systems. Temperature rise
      and fluid velocities in 2D Gaussian-shaped constrictions were studied
      experimentally with supporting analytical estimations and numerical simulations.
      Additionally, we show qualitatively distinct recirculating flow patterns in 2D
      and 3D microchannel constrictions used for iDEP systems. Approximate analytical
      expressions for electrothermal and ICEO velocity scales are provided as a
      function of constriction geometry, bulk electrolyte concentration, and the
      applied electric field. Insights from this study will be useful in designing
      microfluidic systems for electrokinetic particle manipulation.

PMID- 28763136
TI  - The effects of stress and sex on selection, genetic covariance, and the
      evolutionary response.
AB  - The capacity of a population to adapt to selection (evolvability) depends on
      whether the structure of genetic variation permits the evolution of fitter trait
      combinations. Selection, genetic variance and genetic covariance can change under
      environmental stress, and males and females are not genetically independent, yet
      the combined effects of stress and dioecy on evolvability are not well
      understood. Here, we estimate selection, genetic (co)variance and evolvability in
      both sexes of Tribolium castaneum flour beetles under stressful and benign
      conditions, using a half-sib breeding design. Although stress uncovered
      substantial latent heritability, stress also affected genetic covariance, such
      that evolvability remained low under stress. Sexual selection on males and
      natural selection on females favoured a similar phenotype, and there was positive
      intersex genetic covariance. Consequently, sexual selection on males augmented
      adaptation in females, and intralocus sexual conflict was weak or absent. This
      study highlights that increased heritability does not necessarily increase
      evolvability, suggests that selection can deplete genetic variance for
      multivariate trait combinations with strong effects on fitness, and tests the
      recent hypothesis that sexual conflict is weaker in stressful or novel
      environments.

PMID- 28763138
TI  - Mini grasping basket forceps for endobronchial foreign body removal in pediatric
      patients.
AB  - BACKGROUND: Appropriate device selection is crucial for endobronchial foreign
      body removal using a bronchoscope. In pediatric patients, bronchoscopy requires
      the use of a thin device due to the narrow access to the airway, limiting the
      range of useful endobronchial devices. We herein review our experience in
      endobronchial foreign body removal with a focus on the type of bronchoscope and
      the instruments used in comparison with the literature, and investigate the
      utility of mini grasping basket forceps (FG-55D, Olympus(r) ; and Zero TipTM ,
      Airway Retrieval Basket, Boston Scientific). METHODS: Between April 2008 and
      April 2016, foreign bodies were removed from the airway of 12 pediatric patients
      by bronchoscopy. These cases are reviewed in this study. The clinical
      presentation, location and characteristics of the foreign bodies, and the type of
      bronchoscope and instruments used were analyzed. RESULTS: A consecutive series of
      12 pediatric patients was retrospectively reviewed, and the therapeutic
      characteristics investigated. Nuts were the most frequently observed foreign
      body. Seven of the 12 pediatric patients required an ultrathin bronchoscope
      (diameter, 2.8 mm) for foreign body removal. Only one patient required a rigid
      scope in addition to flexible bronchoscopy. The most frequently used instrument
      was a mini grasping basket forceps (n = 7; 58%), which was used with a 1.2 mm
      instrument channel (n = 4; 33%). CONCLUSIONS: The use of a mini grasping basket
      forceps in combination with an ultrathin flexible bronchoscope was useful for
      removing smooth, soft materials such as a nuts or beans in pediatric cases.

PMID- 28763137
TI  - Cognitive function and patient-reported memory problems after radiotherapy for
      cancers at the skull base: A cross-sectional survivorship study using the
      Telephone Interview for Cognitive Status and the MD Anderson Symptom Inventory
      Head and Neck Module.
AB  - BACKGROUND: Using patient-reported and objective assessment tools, we sought to
      quantify cognitive symptoms and objective cognitive dysfunction in patients
      irradiated for skull base cancer. METHODS: Participants were assessed using the
      Telephone Interview for Cognitive Status (TICS) and the MD Anderson Symptom
      Inventory-Head and Neck module (MDASI-HN), with subsequent analysis. RESULTS: Of
      the 122 participants analyzed, the majority (63%) had no frank detectable
      cognitive impairment by TICS, with frank impairment in 6%. Overall, mean patient
      reported problems with memory (MDASImemory ) was 3.3 (SD +/-2.66). On recursive
      partition analysis, the MDASImemory cutoff point of >=5 was associated with
      detectable cognitive impairment by TICS (logworth 1.69; P = .02), yet no
      MDASImemory threshold was associated with unambiguous absence of impairment by
      TICS. CONCLUSION: Approximately one third of patients had ambiguous results by
      TICS assessment, for whom more rigorous testing may be warranted. Moderate to
      severe levels of patient-reported memory complaints on the MDASI-HN module may
      have utility as a screening tool for cognitive dysfunction in this population.

PMID- 28763140
TI  - Necroptosis in the periodontal homeostasis: Signals emanating from dying cells.
AB  - Periodontal tissues are constantly exposed to microbial stimuli. The equilibrium
      between microbes and host defense system helps maintain the homeostasis in the
      periodontal microenvironment. Growth of pathogenic bacteria in dental biofilms
      may induce proinflammatory cytokine production to recruit sentinel cells, mainly
      neutrophils and monocytes into the gingival sulcus or the periodontal pocket.
      Moreover, dysbiosis with overgrowth of anaerobic pathogens, such as Porphyromonas
      gingivalis and Tannerella forsythia, may induce death of both immune cells and
      host resident cells. Necroptosis is one newly characterized programmed cell death
      mediated by receptor-interacting protein kinase (RIPK)-1, RIPK3, and mixed
      lineage kinase like (MLKL). With its release of death-associated molecular
      patterns (DAMPs) into extracellular environment, necroptosis may help transmit
      the danger signal and amplify the inflammatory responses. In this review, we
      present recent advances on how necroptosis influences bacterial infection
      progression and what a role necroptosis plays in maintaining the homeostasis in
      the periodontal niche. Until we fully decipher the signals emanated from dying
      cells, we cannot completely understand the mechanism of disease progression.

PMID- 28763139
TI  - Tumor endothelial cells accelerate tumor metastasis.
AB  - Tumor metastasis is the main cause of cancer-related death. Understanding the
      molecular mechanisms underlying tumor metastasis is crucial to control this fatal
      disease. Several molecular pathways orchestrate the complex biological cell
      events during a metastatic cascade. It is now well known that bidirectional
      interaction between tumor cells and their microenvironment, including tumor
      stroma, is important for tumor progression and metastasis. Tumor stromal cells,
      which acquire their specific characteristics in the tumor microenvironment,
      accelerate tumor malignancy. The formation of new blood vessels, termed as tumor
      angiogenesis, is a requirement for tumor progression. Tumor blood vessels supply
      nutrients and oxygen and also provide the route for metastasis. Tumor endothelial
      cells, which line tumor blood vessels, also exhibit several altered phenotypes
      compared with those of their normal counterparts. Recent studies have emphasized
      "angiocrine factors" that are released from tumor endothelial cells and promote
      tumor progression. During intravasation, tumor cells physically contact tumor
      endothelial cells and interact with them by juxtacrine and paracrine signaling.
      Recently, we observed that in highly metastatic tumors, tumor endothelial cells
      interact with tumor cells by secretion of a small leucine-rich repeat
      proteoglycan known as biglycan. Biglycan from tumor endothelial cells stimulates
      the tumor cells to metastasize. In the present review, we highlight the role of
      tumor stromal cells, particularly endothelial cells, in the initial steps of
      tumor metastasis.

PMID- 28763141
TI  - Charge transfer excitations in TDDFT: A ghost-hunter index.
AB  - This work presents a new index, MAC , enabling the on-the-fly detection of ghost
      charge transfer (CT) states, a major problem in time-dependent density-functional
      theory calculations. This computationally inexpensive index, derived as a
      modification of the Mulliken estimation of transition energy for CT excitations,
      relies on two basic ingredients: an effective CT distance, computed using our
      density-based index (DCT ), and an orbital weighted estimation of the Ionization
      Potential and Electron Affinity. Some model systems, representative of both
      intermolecular and intramolecular CT excitations, were chosen as test cases. The
      robustness of our approach was verified by analyzing the behavior of functionals
      belonging to different classes (GGA, global hybrids and range separated hybrids).
      The results obtained show that ghost states are correctly spotted, also in the
      delicate case of intramolecular excitations displaying substantial donor-bridge
      acceptor delocalization, in a regime for which the standard Mulliken formulation
      attends its limits. (c) 2017 Wiley Periodicals, Inc.

PMID- 28763142
TI  - Neodymium(III) Complexes Capable of Multi-Electron Redox Chemistry.
AB  - A family of neodymium complexes featuring a redox-active ligand in three
      different oxidation states has been synthesized, including the iminoquinone (L0 )
      derivative, (dipp iq)2 NdI3 (1-iq), the iminosemiquinone (L1- ) compound, (dipp
      isq)2 NdI(THF) (1-isq), and the amidophenolate (L2- ) [K(THF)2 ][(dipp ap)2
      Nd(THF)2 ] (1-ap) and [K(18-crown-6)][(dipp ap)2 Nd(THF)2 ] (1-ap crown) species.
      Full spectroscopic and structural characterization of each derivative established
      the +3 neodymium oxidation state with redox chemistry occurring at the ligand
      rather than the neodymium center. Oxidation with elemental chalcogens showed the
      reversible nature of the ligand-mediated reduction process, forming the
      iminosemiquinone metallocycles, [K(18-crown-6)][(dipp isq)2 Nd(S5 )] (2-isq
      crown) and [K(18-crown-6)(THF)][(dipp isq)2 Nd(Se5 )] (3-isq crown), which are
      characterized to contain a 6-membered twist-boat ring.

PMID- 28763143
TI  - Single Graphene Layer on Pt(111) Creates Confined Electrochemical Environment via
      Selective Ion Transport.
AB  - Graphene is a promising candidate for an ideal membrane material. Its ultralow
      (one-atomic) thickness potentially provides high permeation and at the same time
      high selectivity. Here, it is shown that these properties can be used to create a
      confined, two-dimensional electrochemical environment between a graphene layer
      and a single-crystal Pt(111) surface. The well-defined fingerprint voltammetric
      characteristics of Pt(111) provide an immediate information about the penetration
      and intercalation of ions into the confined space. These processes are shown to
      be highly selective.

PMID- 28763144
TI  - A 2-O-Methylriboside Unknown Outside the RNA World Contains Arsenic.
AB  - Lipid-soluble arsenic compounds, also called arsenolipids, are ubiquitous marine
      natural products of currently unknown origin and function. In our search for
      clues about the possible biological roles of these compounds, we investigated
      arsenic metabolism in the unicellular green alga Dunaliella tertiolecta, and
      discovered an arsenolipid fundamentally different from all those previously
      identified; namely, a phytyl 5-dimethylarsinoyl-2-O-methyl-ribofuranoside. The
      discovery is of particular interest because 2-O-methylribosides have, until now,
      only been found in RNA. We briefly discuss the significance of the new lipid in
      biosynthesis and arsenic biogeochemical cycling.

PMID- 28763146
TI  - A Metallosupramolecular Shape-Memory Polymer with Gradient Thermal Plasticity.
AB  - Solid-state plasticity by dynamic covalent bond exchange in a shape-memory
      polymer network bestows a permanent shape reconfiguration ability. Spatio
      selective control of thermally induced plasticity may further extend the
      capabilities of materials into unexplored domains. However, this is difficult to
      achieve because of the lack of spatio-control in typical polymer network
      synthesis. Metal-ligand interactions possess the high strength of covalent bonds
      while maintaining the dynamic reversibility of supramolecular bonds.
      Metallosupramolecular shape-memory polymer networks were designed and prepared,
      which demonstrated solid-state plasticity. The metallo-coordination bonds within
      these networks permit facile tuning of the plasticity behavior across a wide
      temperature range, simply by changing the metal ion. By controlling the diffusion
      of two different metal ions during preparation of a polymer film, a plasticity
      behavior with a spatial gradient was achieved, providing a unique shape-morphing
      versatility with potential in shape-memory devices.

PMID- 28763145
TI  - Phase II study of S-1 plus leucovorin in patients with metastatic colorectal
      cancer: Regimen of 1 week on, 1 week off.
AB  - A phase II study of S-1 plus leucovorin (LV) given in a 4-week schedule (2 weeks'
      administration followed by 2 weeks' rest) for patients with untreated metastatic
      colorectal cancer (mCRC) showed that the combination was effective, but grade 3
      toxicities (diarrhea, stomatitis and anorexia) occurred at a relatively high
      rate. In this phase II study, we evaluated the efficacy and safety of a 2-week
      schedule of S-1 plus LV. Patients with mCRC received oral S-1 (40-60 mg) and LV
      (25 mg) twice daily for 1 week, followed by 1 week's rest. Treatment was repeated
      until disease progression or unacceptable toxicity. The primary endpoint was
      response rate. The pharmacokinetics of S-1 and LV in Chinese patients were
      evaluated on day 1 of the first cycle. Seventy-three patients were enrolled in
      Japan and China. Of 71 eligible patients, the response rate was 53.5%, and the
      disease control rate was 83.1%. Median progression-free survival and median
      overall survival were 6.5 and 24.3 months, respectively. The incidences of grade
      3 toxicities were diarrhea 8.3%, stomatitis 8.3%, anorexia 2.8% and neutropenia
      9.7%. There were no treatment-related deaths. The pharmacokinetics profiles of S
      1 plus LV in Chinese patients were similar to those in Japanese patients. This 2
      week schedule of S-1 plus LV showed good efficacy and better tolerability than
      the 4-week schedule. This therapy will be the base regimen for mCRC to be added
      by other cytotoxic or molecular-targeted drugs. The optimized treatment schedule
      for S-1 plus LV was 1 week on and 1 week off.

PMID- 28763147
TI  - 4,5,9,10-Pyrene Diimides: A Family of Aromatic Diimides Exhibiting High Electron
      Mobility and Two-Photon Excited Emission.
AB  - The design and synthesis of high-performance n-type organic semiconductors are
      important for the development of future organic optoelectronics. Facile synthetic
      routes to reach the K-region of pyrene and produce 4,5,9,10-pyrene diimide (PyDI)
      derivatives are reported. The PyDI derivatives exhibited efficient electron
      transport properties, with the highest electron mobility of up to 3.08 cm2  V-1 
      s-1 . The tert-butyl-substituted compounds (t-PyDI) also showed good one- and two
      photon excited fluorescence properties. The PyDI derivatives are a new family of
      aromatic diimides that may exhibit both high electron mobility and good light
      emitting properties, thus making them excellent candidates for future
      optoelectronics.

PMID- 28763148
TI  - Contribution of diffusion-weighted imaging to dynamic contrast-enhanced MRI in
      the characterization of papillary breast lesions.
AB  - Papillary lesions have a broad spectrum of appearances on magnetic resonance
      imaging (MRI). The purpose of this study was to evaluate whether apparent
      diffusion coefficient (ADC) values of papillary lesions can be used to
      characterize lesion as benign or malignant. This retrospective study included 29
      papillary lesions. Diagnostic values of dynamic contrast-enhanced MRI (DCE-MRI),
      DWI-ADC, and DCE-MRI plus DWI-ADC were separately calculated. The malignant
      papillary lesions (0.744*10-3  mm2 /s) exhibited significantly lower mean ADC
      values than the benign lesions (1.339*10-3  mm2 /s). Addition of DWI to standard
      DCE-MRI provided 100% sensitivity. We hypothesized that this combination may
      prevent unnecessary excisional biopsies.

PMID- 28763149
TI  - Three cases of multi-generational Pompe disease: Are current practices missing
      diagnostic and treatment opportunities?
AB  - Pompe disease (Glycogen storage disease type II, GSDII, or acid maltase
      deficiency) is an autosomal recessive metabolic myopathy with a broad clinical
      spectrum, ranging from infantile to late-onset presentations. In 2015, Pompe
      disease was added as a core condition to the Recommended Uniform Screening Panel
      for state newborn screening (NBS). The clinical importance of Pompe disease is
      evolving with the use of NBS, increasing awareness of the disease, and higher
      than previously reported disease prevalence; however, current practices miss
      additional diagnostic and potential treatment opportunities in close relatives of
      the family proband. In this report, we describe three families with multiple
      individuals in multiple generations affected by both infantile and late-onset
      clinical presentations of Pompe disease. The presence of multi-generational
      disease within these families highlights the importance of subsequent risk
      assessment through medical history and physical examination, with a low threshold
      for the screening of a proband's family members. We recommend enzymology (GAA
      activity assay) as the first screening method, as opposed to targeted mutation
      analysis, for at-risk family members. Given that the initial symptoms of the
      slowly progressive late-onset presentation of Pompe disease may be mild or non
      specific, enzymatic testing of all parents of affected infants should be
      considered.

PMID- 28763150
TI  - Pneumonia in the tropics.
AB  - Pneumonia in the tropics poses a heavy disease burden. The complex interplay of
      climate change, human migration influences and socio-economic factors lead to
      changing patterns of respiratory infections in tropical climate but also
      increasingly in temperate countries. Tropical and poorer countries, especially
      South East Asia, also bear the brunt of the global tuberculosis (TB) pandemic,
      accounting for almost one-third of the burden. But, as human migration patterns
      evolve, we expect to see more TB cases in higher income as well as temperate
      countries, and rise in infections like scrub typhus from ecotourism activities.
      Fuelled by the ease of air travel, novel zoonotic infections originating from the
      tropics have led to global respiratory pandemics. As such, clinicians worldwide
      should be aware of these new conditions as well as classical tropical bacterial
      pneumonias such as melioidosis. Rarer entities such as co-infections of
      leptospirosis and chikungunya or dengue will need careful consideration as well.
      In this review, we highlight aetiologies of pneumonia seen more commonly in the
      tropics compared with temperate regions, their disease burden, variable clinical
      presentations as well as impact on healthcare delivery.

PMID- 28763151
TI  - Supramolecular Architecture of Substituted Tetraphenyl-carbo-benzenes from the
      Energetic Viewpoint.
AB  - The use of DFT-calculated energy-vector diagrams (EVDs) featuring the topology of
      pairwise intermolecular interaction energies is applied to crystals of carbo
      benzenes. A homogeneous set of six ideally centrosymmetric tetraphenyl-carbo
      benzenes is selected, with various substituents R in para positions: R=4-anisyl,
      1-ethyl-2-phenyl-1H-indol-3-yl, 2-chloro-2-(1-ethyl-2-phenyl-1H-indol-3
      yl)ethenyl, tetradecyl, and 9,9-dihexyl-9H-fluoren-2-yl, 2-(9,9-dihexyl-9H
      fluoren-2-yl)ethynyl. The basic structural motifs (BSMs) of the crystals vary
      from layers to columns, depending on the size and shape of the substituents R.
      The BSM cohesion is shown to rely on pi-stacking, CH-pi and dispersive
      interactions. Solvate molecules are shown to have a negligible role in the
      formation of the BSM, whereas they loosen the interaction between neighbouring
      BSMs.

PMID- 28763152
TI  - Beyond Bleaney's Theory: Experimental and Theoretical Analysis of Periodic Trends
      in Lanthanide-Induced Chemical Shift.
AB  - A detailed analysis of paramagnetic NMR shifts in a series of isostructural
      lanthanide complexes relavant to PARASHIFT contrast agents reveals unexpected
      trends in the magnetic susceptibility anisotropy that cannot be explained by the
      commonly used Bleaney's theory. Ab initio calculations reveal that the primary
      assumption of Bleaney's theory-that thermal energy is larger than the ligand
      field splitting-does not hold for the lanthanide complexes in question, and
      likely for a large fraction of lanthanide complexes in general. This makes the
      orientation of the magnetic susceptibility tensor differ significantly between
      complexes of different lanthanides with the same ligand: one of the most popular
      assumptions about isostructural lanthanide series is wrong.

PMID- 28763153
TI  - Prepectoral implant-based breast reconstruction; complete acellular dermal matrix
      wrap or anterior circumferential cover.

PMID- 28763154
TI  - Best practices in peri-operative management of patients with skeletal dysplasias.
AB  - Patients with skeletal dysplasia frequently require surgery. This patient
      population has an increased risk for peri-operative complications related to the
      anatomy of their upper airway, abnormalities of tracheal-bronchial morphology and
      function; deformity of their chest wall; abnormal mobility of their upper
      cervical spine; and associated issues with general health and body habitus.
      Utilizing evidence analysis and expert opinion, this study aims to describe best
      practices regarding the peri-operative management of patients with skeletal
      dysplasia. A panel of 13 multidisciplinary international experts participated in
      a Delphi process that included a thorough literature review; a list of 22
      possible care recommendations; two rounds of anonymous voting; and a face to face
      meeting. Those recommendations with more than 80% agreement were considered as
      consensual. Consensus was reached to support 19 recommendations for best pre
      operative management of patients with skeletal dysplasia. These recommendations
      include pre-operative pulmonary, polysomnography; cardiac, and neurological
      evaluations; imaging of the cervical spine; and anesthetic management of patients
      with a difficult airway for intubation and extubation. The goals of this
      consensus based best practice guideline are to provide a minimum of standardized
      care, reduce perioperative complications, and improve clinical outcomes for
      patients with skeletal dysplasia.

PMID- 28763155
TI  - Multigenerational analyses in perinatal epidemiology.

PMID- 28763156
TI  - Distribution of muscle fibre conduction velocity for representative samples of
      motor units in the full recruitment range of the tibialis anterior muscle.
AB  - AIM: Motor units are recruited in an orderly manner according to the size of
      motor neurones. Moreover, because larger motor neurones innervate fibres with
      larger diameters than smaller motor neurones, motor units should be recruited
      orderly according to their conduction velocity (MUCV). Because of technical
      limitations, these relations have been previously tested either indirectly or in
      small motor unit samples that revealed weak associations between motor unit
      recruitment threshold (RT) and MUCV. Here, we analyse the relation between MUCV
      and RT for large samples of motor units. METHODS: Ten healthy volunteers
      completed a series of isometric ankle dorsiflexions at forces up to 70% of the
      maximum. Multi-channel surface electromyographic signals recorded from the
      tibialis anterior muscle were decomposed into single motor unit action
      potentials, from which the corresponding motor unit RT, MUCV and action potential
      amplitude were estimated. Established relations between muscle fibre diameter and
      CV were used to estimate the fibre size. RESULTS: Within individual subjects, the
      distributions of MUCV and fibre diameters were unimodal and did not show distinct
      populations. MUCV was strongly correlated with RT (mean (SD) R2  = 0.7 (0.09), P
      < 0.001; 406 motor units), which supported the hypothesis that fibre diameter is
      associated with RT. CONCLUSION: The results provide further evidence for the
      relations between motor neurone and muscle fibre properties for large samples of
      motor units. The proposed methodology for motor unit analysis has also the
      potential to open new perspectives in the study of chronic and acute
      neuromuscular adaptations to ageing, training and pathology.

PMID- 28763157
TI  - A unifying mathematical model of lipid droplet metabolism reveals key molecular
      players in the development of hepatic steatosis.
AB  - The liver responds to elevated plasma concentrations of free fatty acids (FFAs)
      with an enhanced uptake of FFAs and their esterification to triacylglycerol
      (TAG). On the long term, this may result in massive hepatic TAG accumulation
      called steatosis hepatitis. In hepatocytes, the poor water-soluble TAG is packed
      in specialized organelles: Lipid droplets (LDs) serving as transient cellular
      deposit and lipoproteins (LPs) transporting TAG and cholesterol esters to extra
      hepatic tissues. The dynamics of these organelles is controlled by a variety of
      regulatory surface proteins (RSPs). Assembly and export of VLDLs are mainly
      regulated by the microsomal transfer protein (MTP) and apoprotein B100. Formation
      and lipolysis of LDs are regulated by several RSPs. The best studied regulators
      belong to the PAT (Perilipin/Adipophilin/TIP47) and CIDE families. Knockdown or
      overexpression of SRPs may significantly affect the total number and size
      distribution of LDs. Intriguingly, a large cell-to-cell heterogeneity with
      respect to the number and size of LDs has been found in various cell types
      including hepatocytes. These findings suggest that the extent of cellular lipid
      accumulation is determined not only by the imbalance between lipid supply and
      utilization but also by variations in the expression of RSPs and metabolic
      enzymes. To better understand the relative regulatory impact of individual
      processes involved in the cellular TAG turnover, we developed a comprehensive
      kinetic model encompassing the pathways of the fatty acid and triglyceride
      metabolism and the main molecular processes governing the dynamics of LDs. The
      model was parametrized such that a large number of experimental in vitro and in
      vivo findings are correctly recapitulated. A control analysis of the model
      revealed that variations in the activity of FFA uptake, diacylglycerol
      acyltransferase (DGAT) 2, and adipose triglyceride lipase (ATGL) have the
      strongest influence on the cellular TAG level. We used the model to simulate LD
      size distributions in human hepatoma cells and hepatocytes exposed to a challenge
      with FFAs. A random fold change by a factor of about two in the activity of RSPs
      was sufficient to reproduce the large diversity of droplet size distributions
      observed in individual cells. Under the premise that the same extent of
      variability of RSPs holds for the intact organ, our model predicts variations in
      the TAG content of individual hepatocytes by a factor of about 3-6 depending on
      the nutritional regime. Taken together, our modeling approach integrates numerous
      experimental findings on individual processes in the cellular TAG metabolism and
      LD dynamics metabolism to a consistent state-of-the-art dynamic network model
      that can be used to study how changes in the external conditions or systemic
      parameters will affect the TAG content of hepatocytes.

PMID- 28763158
TI  - Frequency and number of B-lines using a regionally based lung ultrasound
      examination in cats with radiographically normal lungs compared to cats with left
      sided congestive heart failure.
AB  - OBJECTIVE: To establish a baseline lung ultrasound (LUS) artifact profile using a
      regionally based protocol in cats without clinical signs of respiratory disease
      and with radiographically normal lungs compared to a cohort of cats with left
      sided congestive heart failure (CHF). DESIGN: Prospective case series. ANIMALS:
      Forty-nine cats without clinical signs of respiratory disease and with
      radiographically normal lungs and 7 cats with radiographic evidence of left-sided
      CHF. INTERVENTIONS: Application of a previously published LUS protocol. Frequency
      of B-lines was compared based on signalment, body condition score, investigator,
      and reasons for radiography and between 49 cats with radiographically normal
      lungs to 7 cats with radiographic evidence of left-sided CHF. RESULTS: Overall
      frequency of B-lines was 12% (95% confidence interval, 5-24%) in cats without
      respiratory disease versus 100% (95% confidence interval, 65-100%) in those with
      left-sided CHF. Six cats (6/49) had B-lines with 5/6 having B-lines at a single
      site; and 4/5 having a single B-line at 1 site, 1/5 having 2 B-lines at 1 site;
      and the sixth cat having 2 positive sites with a single B-line at each. In the
      cohort of cats with left-sided CHF, all cats (7/7) had >3 B-lines detected at
      every site. CONCLUSIONS: The lack of B-lines in cats without respiratory disease
      (with radiographically normal lungs) and the predominance of B-lines in cats with
      left-sided CHF suggest that a regionally based LUS protocol may be clinically
      useful for the identification and evaluation of feline respiratory conditions.

PMID- 28763159
TI  - Examining the diagnostic utility of the DSM-5 PTSD symptoms among male and female
      returning veterans.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) diagnostic criteria have been
      criticized for including symptoms that overlap with commonly comorbid disorders,
      which critics argue undermines the validity of the diagnosis and inflates
      psychiatric comorbidity rates. In response, the upcoming 11th edition of the
      International Classification of Diseases (ICD-11) will offer PTSD diagnostic
      criteria that are intended to promote diagnostic accuracy. However, diagnostic
      utility analyses have not yet assessed whether these criteria minimize diagnostic
      errors. The present study examined the diagnostic utility of each PTSD symptom in
      the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders
      (DSM-5) for males and females. METHODS: Participants were 1,347 individuals
      enrolled in a longitudinal national registry of returning veterans receiving care
      at a Department of Veterans Affairs (VA) facility. Doctoral level clinicians
      assessed all participants using the PTSD module of the Structured Clinical
      Interview for DSM. RESULTS: Of the 20 symptoms examined, the majority performed
      in the fair to poor range on test quality indices. Although a few items did
      perform in the good (or better) range, only half were ICD-11 symptoms. None of
      the 20 symptoms demonstrated good quality of efficiency. Results demonstrated few
      sex differences across indices. There were no differences in the proportion of
      comorbid psychiatric disorders or functional impairment between DSM-5 and ICD-11
      criteria. CONCLUSIONS: ICD-11 PTSD criteria demonstrate neither greater
      diagnostic specificity nor reduced rates of comorbidity relative to DSM-5
      criteria and, as such, do not perform as intended. Modifications to existing
      symptoms or new symptoms may improve differential diagnosis.

PMID- 28763160
TI  - CRISPR/Cas9-mediated targeting of the Rosa26 locus produces Cre reporter rat
      strains for monitoring Cre-loxP-mediated lineage tracing.
AB  - The rat is an important laboratory animal for physiological, toxicological and
      pharmacological studies. Clustered regularly interspaced short palindromic
      repeats (CRISPR)/CRISPR-associated 9 (Cas9) is a simple and efficient tool to
      generate precise genetic modifications in rats, which will promote the
      accumulation of genetic resources and enable more precise studies of gene
      function. To monitor Cre-loxP-mediated excision in vivo, we generated a Cre
      reporter rat strain (Rosa26-imCherry) by knockin of a Cre reporter cassette at
      the Rosa26 locus using CRISPR/Cas9. Rosa26-imCherry rats exhibited inducible
      expression of the mCherry cassette (imCherry) using the Cre-loxP system, whereas
      normal rats exhibited ubiquitous expression of eGFP but not mCherry in the whole
      body. Injection of adeno-associated virus serotype 9-Cre into the hippocampus and
      skeletal muscle resulted in mCherry expression in virus-infected cells. Cre-loxP
      mediated mCherry expression was then evaluated by crossing Rosa26-imCherry rats
      with transgenic rats ubiquitously expressing CAG-Cre, heart-specific alpha-MHC
      Cre transgenic rats and liver-specific Alb-Cre knockin rats. Finally, using the
      established system the expression pattern of Cre driven by two endogenous gene
      promoters (Wfs1-Cre knockin rat, FabP2-Cre knockin rat) was traced. In summary,
      we demonstrated excision of the loxP-flanked allele in Rosa26-imCherry rats via
      activation of mCherry expression in the presence of Cre recombinase. This newly
      established Rosa26-imCherry rat strain represents a useful tool to facilitate Cre
      expression pattern determination and tracing experiments.

PMID- 28763161
TI  - Monoallelic FGFR3 and Biallelic ALPL mutations in a Thai girl with
      hypochondroplasia and hypophosphatasia.
AB  - Skeletal dysplasias are a complex group of more than 350 disorders with
      phenotypic and genotypic heterogeneity affecting bone and cartilage growth. We
      studied a 2-year-old girl and her 21-year-old mother with disproportionate short
      stature. In addition to typical features of hypochondroplasia found in both
      patients, the child had deformities of the extremity bones, metaphyseal flares,
      and bilateral transverse (Bowdler) fibular spurs with overlying skin dimples
      detected at birth. Intravenous pamidronate was started in the child since the age
      of 17 days, and then every two months. Exome sequencing revealed that the girl
      was heterozygous for a missense mutation (c.1651A>G, p.Ile538Val) in exon 13 of
      FGFR3, a known mutation for hypochondroplasia, inherited from her mother.
      Interestingly, the child also harbored compound heterozygous missense mutations
      in exon 12 of ALPL, c.1460C>T (p.Ala487Val) inherited from her mother and
      c.1479C>A (p.Asn493Lys) inherited from her healthy father. The former mutation
      was previously reported in perinatal hypophosphatasia while the latter was novel.
      Constantly reduced serum alkaline phosphatase levels including the one before the
      pamidronate administration and a substantially elevated level of plasma pyridoxal
      5'-phosphate detected at age 28 months supported the diagnosis of
      hypophosphatasia. After a definite diagnosis was achieved, pamidronate was
      withdrawn at the age of 28 months. No adverse events were observed during
      pamidronate therapy. In conclusion, we describe a unique case with monoallelic
      FGFR3 and biallelic ALPL mutations leading to features of both hypochondroplasia
      and hypophosphatasia.

PMID- 28763162
TI  - Cobalt-Manganese Mixed-Sulfide Nanocages Encapsulated by Reduced Graphene Oxide:
      In Situ Sacrificial Template Synthesis and Superior Lithium Storage Properties.
AB  - This work demonstrates a facile in situ synthesis of cobalt-manganese mixed
      sulfide (CoMn-S) nanocages on reduced graphene oxide (RGO) sheets by using a
      crystalline Co-Mn precursor as the sacrificial template. The CoMn-S/RGO hybrid
      was applied as the anode for Li-ion storage and exhibited superior specific
      capacity, excellent cycling performance, and great rate capability. In
      particular, lithium storage testing revealed that the hybrid delivered high
      discharge-charge capacities of 670 mA h g-1 at 1.0 A g-1 after 400 cycles and 925
      mA h g-1 at 0.1 A g-1 after 300 cycles. The outstanding electrochemical
      performance of CoMn-S/RGO is attributed to the close entanglement of nanocages
      with RGO nanosheets achieved by the synthetic method, which greatly improves
      ion/electron transport along the interfaces and efficiently mitigates volume
      dilation during lithium reactions. This rational design of both the composition
      and architecture of mixed metal sulfides can be expanded to other composite
      systems for high-capacity Li-ion batteries and provides a unique insight into the
      development of advanced hybrid electrode materials.

PMID- 28763163
TI  - Professor Bezhan Chankvetadze turns 60.

PMID- 28763166
TI  - Comparison of three methods for the methylation of aliphatic and aromatic
      compounds.
AB  - RATIONALE: Methylation protocols commonly call for acidic, hot conditions that
      are known to promote organic 1 H/2 H exchange in aromatic and aliphatic C-H
      bonds. Here we tested two such commonly used methods and compared a third that
      avoids these acidic conditions, to quantify isotope effects with each method and
      to directly determine acidic-exchange rates relevant to experimental conditions.
      METHODS: We compared acidic and non-acidic methylation approaches catalyzed by
      hydrochloric acid, acetyl chloride and EDCI (1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide)/DMAP (4-dimethylaminopyridine), respectively.
      These were applied to two analytes: phthalic acid (an aromatic) and octacosanoic
      acid (an aliphatic). We analyzed yield by gas chromatography/flame ionization
      (GC/FID) and hydrogen and carbon isotopic compositions by isotope ratio mass
      spectrometry (GC/IRMS). We quantified the 1 H/2 H exchange rate on dimethyl
      phthalate under acidic conditions with proton nuclear magnetic resonance (1 H
      NMR) measurements. RESULTS: The delta2 H and delta13 C values and yield were
      equivalent among the three methods for methyl octacosanoate. The two acidic
      methods resulted in comparable yield and isotopic composition of dimethyl
      phthalate; however, the non-acidic method resulted in lower delta2 H and delta13
      C values perhaps due to low yields. Concerns over acid-catalyzed 1 H/2 H exchange
      are unwarranted as the effect was trivial over a 12-h reaction time. CONCLUSIONS:
      We find product isolation yield and evaporation to be the main concerns in the
      accurate determination of isotopic composition. 1 H/2 H exchange reactions are
      too slow to cause measurable isotope fractionation over the typical duration and
      reaction conditions used in methylation. Thus, we are able to recommend continued
      use of acidic catalysts in such methylation reactions for both aliphatic and
      aromatic compounds.

PMID- 28763165
TI  - A pesticide paradox: fungicides indirectly increase fungal infections.
AB  - There are many examples where the use of chemicals have had profound unintended
      consequences, such as fertilizers reducing crop yields (paradox of enrichment)
      and insecticides increasing insect pests (by reducing natural biocontrol).
      Recently, the application of agrochemicals, such as agricultural disinfectants
      and fungicides, has been explored as an approach to curb the pathogenic fungus,
      Batrachochytrium dendrobatidis (Bd), which is associated with worldwide amphibian
      declines. However, the long-term, net effects of early-life exposure to these
      chemicals on amphibian disease risk have not been thoroughly investigated. Using
      a combination of laboratory experiments and analysis of data from the literature,
      we explored the effects of fungicide exposure on Bd infections in two frog
      species. Extremely low concentrations of the fungicides azoxystrobin,
      chlorothalonil, and mancozeb were directly toxic to Bd in culture. However,
      estimated environmental concentrations of the fungicides did not reduce Bd on
      Cuban tree frog (Osteopilus septentrionalis) tadpoles exposed simultaneously to
      any of these fungicides and Bd, and fungicide exposure actually increased Bd
      induced mortality. Additionally, exposure to any of these fungicides as tadpoles
      resulted in higher Bd abundance and greater Bd-induced mortality when challenged
      with Bd post-metamorphosis, an average of 71 d after their last fungicide
      exposure. Analysis of data from the literature revealed that previous exposure to
      the fungicide itraconazole, which is commonly used to clear Bd infections, made
      the critically endangered booroolong frog (Litoria booroolongensis) more
      susceptible to Bd. Finally, a field survey revealed that Bd prevalence was
      positively associated with concentrations of fungicides in ponds. Although
      fungicides show promise for controlling Bd, these results suggest that, if
      fungicides do not completely eliminate Bd or if Bd recolonizes, exposure to
      fungicides has the potential to do more harm than good. To ensure that fungicide
      applications have the intended consequence of curbing amphibian declines,
      researchers must identify which fungicides do not compromise the pathogen
      resistance mechanisms of amphibians.

PMID- 28763167
TI  - Experiences of Antenatal Care Among Women Who Are Socioeconomically Deprived in
      High-Income Industrialized Countries: An Integrative Review.
AB  - INTRODUCTION: Socioeconomic deprivation in high-income industrialized countries
      is a key factor in poor perinatal outcomes. Limited access, utilization, and
      quality of antenatal care seem to play an important role in poor perinatal
      outcomes. METHODS: This integrative review aimed to explore experiences of
      antenatal care among women who are socioeconomically deprived in high-income
      industrialized countries. A search was conducted using 5 databases for articles
      published from 2004 to 2014. Six qualitative and 3 quantitative articles were
      selected. These were systematically appraised for quality independently by 3
      researchers. Relevant themes were identified and organized into categories.
      RESULTS: The disadvantages experienced in antenatal care by women who are
      socioeconomically deprived start before the first contact with health care
      services and are notable throughout the entire pregnancy. There is disparity in
      choice of medical or midwifery service provision models. Six categories emerged
      during review: choice of service provision model, feeling valued, various types
      of discrimination, structural and interpersonal accessibility, comprehensibility
      and trustworthiness of information, and engagement and sense of responsibility.
      Categories underscored the importance of the woman's relationship with the
      antenatal care provider. DISCUSSION: Antenatal care models with women-centered
      approaches and continuity of care, such as midwifery models, have potential to
      increase the satisfaction of women with low socioeconomic status with care; this
      may increase antenatal care utilization and improve perinatal outcomes.

PMID- 28763168
TI  - The Effect of Nonnutritive Sweeteners Added to a Liquid Diet on Volume and
      Caloric Intake and Weight Gain in Rats.
AB  - OBJECTIVE: Long-term effects of diet beverage consumption on the regulation of
      caloric intake is unclear. The goal of this study was to investigate whether the
      chronic intake of a liquid diet with nonnutritive sweeteners (NNS) would lead to
      greater appetite and weight gain. METHODS: Wistar rats were fed a liquid diet
      (Osmolite) sweetened with nutritive sweetener (NS; sucrose) and NNS (stevia and
      saccharin) or a nonsweetened control. Intakes and weight gain were measured.
      Phases 1 and 2 investigated sweetness preference, phase 3 used diets with or
      without sweeteners, and phase 4 measured the effect on volume of food and caloric
      intake of alternating between NNS, NS, and control diets. RESULTS: In phase 1,
      rats preferred: stevia, 0.10%; saccharin, 0.20%; and sucrose, 15%. In phase 2,
      rats preferred the sweetened diet over the control. In phase 3, rats fed the NS
      diet consumed less volume and more calories but gained less weight. In phase 4,
      when altering diet from NNS to NS, no differences were observed in appetite or
      weight gain. CONCLUSIONS: Using sucrose-sweetened diet as a control, increased
      weight gain with the ingestion of NNS was observed. However, using a nonsweetened
      control, neither increased caloric intake nor weight gain occurred with NNS
      intake. Alternating diets between NNS, NS, and control did not affect the
      appetite.

PMID- 28763169
TI  - Evaluating the risk of decompression sickness for a yo-yo dive using a rat model.
AB  - PURPOSE: The frequent ascents made during yo-yo diving may contribute to gas
      bubble clearance but paradoxically may also increase the risk of central nervous
      system decompression illness (DCI). We evaluated the risk of DCI due to yo-yo
      dives with very short surface intervals, using a controlled animal model.
      METHODS: Dives were conducted on air to a depth of 90 meters (10 atmospheres
      absolute) for 32 minutes of bottom time, at a descent/ascent rate of 10 meters/
      minute. Sprague-Dawley rats weighing ~ 300 grams were divided randomly into three
      groups. Group A performed a square dive protocol without any surface intervals,
      Group B conducted a protocol that included two surface intervals during the dive,
      and Group C performed a protocol with three surface intervals. Ascent/descent
      rate for surface intervals, each lasting one minute, was also 10 meters/minute.
      RESULTS: Manifestations of DCI were observed in 13 of 16 animals in Group A
      (81.3%), six of 12 in Group B (58.3%), and two of 12 in Group C (16.7%).
      Mortality rates were similar in all groups. CONCLUSIONS: Surface intervals during
      dives breathing air significantly reduced DCI risk in the rat. Further studies
      are required using a larger animal model to reinforce the results of the present
      investigation.

PMID- 28763170
TI  - Decreasing carbon monoxide in the diving air of artisanal fishermen in the
      Yucatan peninsula by separation of engine exhaust from compressor intake.
AB  - Artisanal fishermen in the Yucatan Peninsula utilize hookah dive systems (HDS).
      The air compressors in these HDS are not filtered, and the intake is near the
      engine exhaust. This proximity allows carbon monoxide (CO) from the exhaust to
      directly enter the HDS volume tank and contaminate the fishermen diver's air
      supply. Conservative safety standards permit a diver's air supply to contain 10
      parts per million (ppm) of CO. This study quantified the levels of CO in the
      diver's air supply both before and after physical separation of the engine
      exhaust from the compressor intake. CO levels in seven volume tanks were analyzed
      before and after a 1-inch hose was attached to the compressor intake and elevated
      5 feet above the engine exhaust. The tanks were drained and refilled before
      collecting each set of pre- and post-intervention gas samples. Four CO
      measurements were collected before and after the intervention from each volume
      tank. A C-Squared(c) CO Analyzer (+/- 1 ppm), calibrated with a Praxair 70 ppm
      CON2 gas (+/- 5%), was used to analyze the gas samples. A paired samples t-test
      shows a statistically significant difference in average CO values before and
      after the intervention (t = 6.8674, df: 27; p?0.0001). The physical separation of
      the engine exhaust from the compressor intake reduced the CO contamination of the
      diver air supply by 72%. This intervention could be applied to the hookah systems
      in the rest of the fishing cooperative to reduce the divers' risk of CO
      poisoning.

PMID- 28763171
TI  - Effects of rapid decompression on HUVECs in vitro.
AB  - OBJECTIVE: To explore the possible effects of rapid decompression on the activity
      and function of vascular endothelial cells in vitro. METHODS: Human umbilical
      vein endothelial cell (HUVEC) cultures were exposed at 7 atmospheres absolute
      (atm abs) air for two hours before decompression. Two decompression profiles were
      used at the rate of 30 atm abs min-1 (rapid decompression) or 1 atm abs min-1
      (normal decompression). Three hours after decompression, cell activity was
      detected by cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH)
      activity assay; cell permeability was measured by electrical resistance
      determinations. Twelve hours after decompression, cell apoptosis was detected by
      flow cytometry with Annexin V FITC/PI double staining. RESULTS: There was no
      significant statistical difference between rapid and normal decompression groups
      in all the determined parameters (P=0.59, 0.87, 0.86 and 0.81, respectively).
      CONCLUSIONS: HUVECs endure rapid decompression well from 7 atm abs at the rate of
      30 atm abs min-1, or the current determinations are not sensitive enough to
      reveal the possible injuries. Further research with more sensitive indexes is
      warranted to reveal the possible effects and mechanisms.

PMID- 28763172
TI  - Applying quality improvement methods in a hyperbaric oxygen program: reducing
      unnecessary glucose testing.
AB  - OBJECTIVE: To describe the implementation of a quality improvement (QI) project
      that aimed at improving and standardizing glucose checks on patients with
      diabetes undergoing hyperbaric oxygen (HBO2) therapy. METHODS: This is a
      prospective cohort study. Following the Model for Improvement, nurses and
      physicians ran several Plan-Do-Study-Act (PDSA) cycles over a four-month period,
      with multiple iteration and testing changes. They developed and implemented a
      nurse-led protocol that was tested prospectively. RESULTS: Compared to the pre
      protocol baseline (N = 332), glucose checks per session guided by the protocol
      decreased by 37.7% (2.84 vs. 1.77 per session, P?0.001). Compliance with the new
      protocol was higher than compliance with the existing protocol (97.3% to 84.2%,
      P?0.001). There were no cases of a symptomatic hypoglycemic event after the
      implementation of the protocol. CONCLUSIONS: A quality improvement project
      implemented by a multidisciplinary team in a hyperbaric practice was feasible and
      has improved the management of diabetic patients undergoing HBO2 therapy.
      Considering how the hyperbaric community values the culture of safety and
      considering the feasibility of this project, more QI training and projects in
      hyperbaric programs should be performed.

PMID- 28763173
TI  - Treatment of hyperoxic acute lung injury with stem cell transplantation in murine
      models: a brief review.
AB  - Hyperoxia has been a prominent clinical concern with the emergence of the
      intensive care unit and prolonged mechanical ventilation, along with the
      increasing use of hyperbaric oxygen therapy. Indeed, prolonged breathing of a
      high oxygen partial pressure may cause hyperoxic acute lung injury (HALI). To
      date, HALI has been a focus in the fields of pediatric and pulmonary medicine.
      However, no effective strategies have been developed for therapy for HALI due to
      the complicated mechanisms underlying the pathogenesis of HALI. In recent years,
      increasing studies have employed cell-based therapy for HALI. In this review, we
      summarize findings from available studies on therapy for HALI using stem cells in
      murine models and, based on concerns in this field, present our findings on cell
      based therapy for HALI.

PMID- 28763174
TI  - Detection of venous gas emboli after repetitive breath-hold dives: case report.
AB  - INTRODUCTION: Neurological symptoms after breathhold (BH) diving are often
      referred to as "Taravana" and considered a form of decompression sickness.
      However, the presence of "high" gas embolism after BH diving has never been
      clearly shown. This study showed high bubble formation after BH diving. MATERIALS
      and METHODS: We performed transthoracic echocardiography on a 53-year-old male
      spearfishing diver (180 cm; 80 kg; BMI 24.7) 15 minutes before diving and at 15
      minute intervals for 90 minutes after diving in a 42-meter-deep pool. Number of
      dives, bottom time and surface intervals were freely determined by the diver.
      Dive profiles were digitally recorded for depth, time and surface interval, using
      a freediving computer. Relative surface interval (surface interval/diving time)
      and gradient factor were calculated. REULTS: High bubble grades were found in all
      the recorded echocardiograms. From the first to third recording (45 minutes),
      Grade 4 Eftedal-Brubakk (EB) bubbles were observed. The 60-, 75- and 90-minute
      recordings showed a reduction to Grades 3, 2 and 1 EB. Mean calculated GF for
      every BH dive was 0.22; maximum GF after the last dive was 0.33. CONCLUSIONS:
      High bubble grades can occur in BH diving, as confirmed by echocardiographic
      investigation. Ordinary methods to predict inert gas supersaturation may not able
      to predict Taravana cases.

PMID- 28763175
TI  - A favorable outcome despite a 39-hour treatment delay for arterial gas embolism:
      case report.
AB  - Cerebral arterial gas embolism (CAGE) occurs when gas enters the cerebral
      arterial vasculature. CAGE can occur during sitting craniotomies, cranial trauma
      or secondary to gas embolism from the heart. A far less common cause of CAGE is
      vascular entrainment of gas during endoscopic procedures. We present the case of
      a 49-year-old male who developed a CAGE following an esophagoduodenoscopy (EGD)
      biopsy. Due to a delay in diagnosis, the patient was not treated with hyperbaric
      oxygen (HBO2) therapy until 39 hours after the inciting event. Despite presenting
      to our institution non-responsive and with decorticate posturing, the patient was
      eventually discharged to a rehabilitation facility, with only mild left upper
      extremity weakness. This delay in HBO2 treatment represents the longest delay in
      treatment to our knowledge for a patient suffering from CAGE secondary to EGD. In
      addition to the clinical case report, we discuss the etiology of CAGE and the
      evidence supporting early HBO2 treatment, as well as the data demonstrating
      efficacy even after considerable treatment delay.

PMID- 28763176
TI  - Patient diagnosed with chronic erectile dysfunction refractory to PDE 5 Inhibitor
      therapy reports improvement in function after hyperbaric oxygen therapy.
AB  - Erectile dysfunction (ED), defined as the inability to achieve or sustain an
      erection firm enough for sexual intercourse, is common in men older than 50 years
      of age whose medical history includes diabetes mellitus. This case report
      describes a male patient treated with hyperbaric oxygen (HBO2) therapy as part of
      a comprehensive wound treatment plan for an open right foot wound. The patient's
      medical history included Type 1 diabetes mellitus and chronic ED refractory to
      previous trials of phosphodiesterase type 5 inhibitors. The patient completed a
      total of 60 HBO2 treatments over a 15-week period. He reported an improvement in
      his ED symptoms after the first 20 hyperbaric treatments, with morning tumescence
      being the first sign of a change. Patient continued to report morning tumescence
      24 weeks after final HBO2 treatment.

PMID- 28763177
TI  - Pain improvement in rheumatoid arthritis with hyperbaric oxygen: report of three
      cases.
AB  - Rheumatoid arthritis (RA) is a chronic, erosive, symmetrical inflammatory disease
      that can progress to synovial destruction, severe disability and premature
      mortality. Immunotherapies, while beneficial, can cause significant adverse
      events. Three patients with RA treated in our facility with hyperbaric oxygen
      (HBO2) for unrelated diagnoses all reported significant but unanticipated
      improvement in RA-related pain, increased activity and improved sleeping
      patterns. Two improved while continuing traditional RA medications; the other
      patient had all RA meds held due to cancer and postoperative wound healing
      problems. The significant symptomatic improvement in these three patients led us
      to hypothesize that HBO2 for patients with RA may result in decreased joint pain,
      increased activity level, improvement in sleeping patterns and possibly a
      decreased need for standard rheumatologic medications, effectively reducing or
      avoiding the effects of immunosuppression. A clinical trial is planned to
      objectively assess these findings.

PMID- 28763178
TI  - HBO2 in snake envenomation (atrox albinus rattlesnake): a case report in a human.
AB  - A patient suffered from an envenomation that, at his hospitalization, was judged
      severe: Grade 3 out of 3, as defined in clinical studies for CroFabTM antidote
      [Crotalidae Polyvalent Immune Fab (Ovine)]. In addition to the usual antivenom
      treatment we applied adjunctive hyperbaric oxygen (HBO2) therapy. Our aim was to
      facilitate better control of the lesions, already presenting as problematic
      wounds and at high risk of necrotizing soft tissue infection with compartment
      aspects. The regimen consisted of six treatments, one daily at 2.4 atmospheres
      absolute at 25 minutes x3 (75 minutes) at FiO2=1, with two five-minute air breaks
      interposed. The therapy was well tolerated in spite of the patient's declared
      trait of claustrophobia. Our findings at a long-term follow up suggest that HBO2
      therapy may be reasonably and effectively administered at least in the post-acute
      phase of such occurrences.

PMID- 28763179
TI  - [Editorial.Italian Code of Ethics for Nurses and ICN International Nursing Day
      2017.]

PMID- 28763180
TI  - [Improving operating room efficiency: an observational and multidimensional
      approach in the San Camillo-Forlanini Hospital, Rome].
AB  - AIM: The management of operating rooms (ORs) is a complex process which requires
      an effective organizational scheme. In order to amore convinient allocation of
      resources a rigorous monitoring plan is needed to ensure operating rooms
      performances. All the necessary actions should be taken to improve the quality of
      the planning and scheduling procedure. METHODS: Between April-December, 2016 an
      organizational analysis has been carried out on the performances of the A.O. S.
      Camillo-Forlanini Hospital Operating Block applying the "process management"
      approach to the ORs efficiency. The project involved two different surgical areas
      of the same operating block the multi-specialist and elective surgery and cardio
      vascular surgery . The analyses of the processes was made through the product,
      patient and safety approach and from different points of view: the "asis",
      process and stakeholder perspectives. Descriptive statistics was used to process
      raw data and Student's t-distribution was used to assess the difference between
      the two means (significant p value ?0,05). The Coefficient of Variation (CV) was
      used to describe the variabilityamong data. RESULTS: The asis approach allowed us
      to describe the ORs inbound activities. For both operating block the most
      demanding weekly commitments in terms of time turned out to be the inventory
      management procedures of controlling and stocking medicines, general medical
      supplies and instruments (130[DS=+/-14] for BOE and 30[DS=+/-18] for CCH. The
      average time spent on preparing the operating room, separately calculated
      starting from the first surgical case, was of 27 minutes (SD=+/- 17) while for
      the following surgical procedures preparation time decreased to 15 minutes (SD=
      +/- 10), which highlighted a meaningful difference of 12 minutes. A great
      variability was registered in CCH due to the unpredictability of these operations
      (CV 82%). The stakeholders' perspective revealed a reasonable level of
      satisfaction among nurses and surgeons (2.9 vs 2.3, respectively) and in
      anesthesiologist (2.8-BOE vs 2.4 CCH).Being brought to the surgical suite from an
      "external Unit" seems to have negatively influenced the patient's perception:
      preparation time turned out to be significantly lower for CCH patients rather
      than BOE ones (p?0,001).The results of the safety procedure approach highlighted
      a moderate criticality in terms of cleaning up time and delay in the starting
      time of the first surgical case. CONCLUSION: More effort should be made to avoid
      any slowdown during the whole process. It is advisable to implement a lean system
      that may improve efficiency and quality of the service to reduce wastes and
      unproductive times. This would inevitably generate a more positive outcomes.

PMID- 28763181
TI  - Distribution and predictive accuracy of the Index of Caring Complexity in a semi
      intensive care unit
AB  - OBJECTIVE: To analyze nursing complexity level and its relationship with
      mortality and length of stay. METHOD: Observational study carried out between
      1/06/2014 to 21/06/2015 at High Dependency Unit of an Italian University
      Hospital. The nursing needs and the Index of Caring Complexity (Indice di
      Complessita Assistenziale, ICA) were collected following the "Modello delle
      Prestazioni Infermieristiche". RESULTS: Data from 506 patients were collected for
      a maximum of 4 days of hospital stay (1,436 data collection). Nursing needs with
      the higher score were mostly related to cardio-circulatory function. Average ICA
      was 38.4. Only 17.2% of patients were classified as "high complexity" at
      admission. During the hospital stay, the ICA showed a progressive decrease in
      survivors while increased in those who died. Overall, the ICA showed high
      predictive accuracy regarding the risk of death (90.3%; p=0.006); the best ICA
      cut-off point was 41.5. DISCUSSION: The risk of death increased with the
      increasing complexity of nursing care. Exceeding the ICA cut-off value, as well
      as an increasing trend in the ICA daily monitoring, may be adopted as criteria to
      identify patients at higher risk, for which increasing, for example, the nurse
      patients ratio. Identification of the patient's complexity level may enable the
      delivery of more personalized nursing activities or interventions based on the
      intensity of care needed, as well as the proper allocation of patients during
      hospitalization. This strategy may allow the rationalization of available
      resources and better planning and implementation of nursing care.

PMID- 28763183
TI  - [The most cited themes in the research in the field of Mental Health: analyses of
      six international nursing and medical journals].
AB  - INTRODUCTION: The review aimed to identify and analyse the future development on
      the topic by analysing the main themes discussed in number of scientific journal
      focused on Mental Health both by nurses and physicians.. METHOD: 4 international
      journals focused on Mental health and psychiatry International Journal of Mental
      Health Nursing, Archives of Psychiatric Nursing, American Journal of Psychiatry,
      Australian and New Zeland Journal of Psychiatry as well as two journal focused
      generically on health, Journal of Advanced Nursing and Lancet were scrutinized.
      We have analysed the papers of 2012-2015 for the specialised journals and last
      and first 6 months of 2012 and 2013 and 2014-2015 for the generic. Editorials,
      comments and contributions regarding theoretical models were exluded. From the
      analysis we identified 9 themes and for each theme the pertinent category. For
      the diagnostic grouping we used the International Statistical Classification of
      Diseases and Related Health Problems 10th Revision. RESULTS: A trend in research
      about mood disorders, schizophrenia and addictions and comorbidity emerged
      according to the 2099 abstracts analysed. Within medical research antidepressants
      were the most studied psychotropic medication and cognitive behaviour therapy was
      the most studied psychotherapy. Within nursing research: the nurse-patient
      relationship, adherence and monitoring of pharmacological therapy, the treatment
      planning and the working environment, the nursing training and its efficacy. The
      clinical research trials were twice as frequent in the medical versus nursing
      research where qualitative research prevails. CONCLUSION: The research challenge
      will be to find a new paradigm fit for the future psychiatry having at its
      disposition the patient's genoma, and needing to routinely use biomarkers for a
      personalised therapy. A further challenge might be the promotion of
      interprofessional research between doctors and nurses and the acquisition of new
      competences of health professionals needed to tackle the reduced life expectancy
      of psychiatric patients and to address not only their mental illnesses but also
      their physical ailments.

PMID- 28763182
TI  - [Multicenter validation of an evaluation tool for clinical training activities
      (SVAT) of the nursing students].
AB  - OBJECTIVE: To evaluate the psychometric characteristics of the Scheda di
      Valutazione delle Attivita di Tirocinio (SVAT). METHOD: The degree courses in
      Nursing of the University of Modena and Reggio Emilia, site of Reggio Emilia, the
      University of Bologna Formative Section BO1, Imola and training center of Cesena,
      the University of Ferrara training centers of Ferrara and Codigoro were all
      enrolled in the research. For the content validation the reactive Delphi method
      was chosen. The panel of experts expressed a qualitative-intuitive judgment on
      the adequacy of language and on the stimulus material (SVAT). For internal
      consistency Cronbach's alpha was calculated the. The test-retest method was used
      for the reliability of stability. RESULTS: all indicators of the SVAT have
      achieved a degree of consensus not less than 80% demonstrating its content
      validity. The face validity is demonstrated by an average score equal to or
      greater than 7 obtained by all indicators. The reliability of internal
      consistency of the SVAT was appraised by Cronbach's alpha that was 0.987 for the
      entire instrument. The reliability of the stability has been calculated through
      the correlation's coefficient expressed by Pearson's r that was 0.983 (p = 1.3E
      198). DISCUSSION: in Italy there is no a "gold standard" tool to evaluate the
      clinical performance of nursing students during and at the end of their clinical
      training. The SVAT proves to be a valuable and reliable tool it furthermore could
      stimulate the discussion and the debate among educators and nurses, so that also
      in our country, it may be possible develop and refine tools that support the
      evaluation of clinical skills of nursing students.

PMID- 28763184
TI  - [Smartphone use in nursing population: a narrative review].
AB  - INTRODUCTION: In healthcare, smartphone is becoming an important tool among
      nursing population. With the smartphones, it was possible to implement new care
      models. However, if used incorrectly, it could be the cause of nurses'
      distraction and nosocomial infection. AIM: To analyze the various apps used by
      the nursing population and describe the smartphones' positive and negative
      aspects on health care by review the literature. METHOD: PubMed, CINAHL, SCOPUS e
      Web of Knowledge, Google Schoolar, databases were used to perform this study. The
      following keywords were used: ((nurse* NOT (student* OR physician*)) AND
      (smartphone* OR phone* OR mobile* OR cellphone) AND (app OR use* OR benefit OR
      distraction OR stress OR abuse OR work-related). RESULTS: A total of 34 articles
      were included in the review. Medical calculation, heart measurement and chronic
      patient-nurse communication apps were described. While smartphones may cause
      distraction, nosocomial infection or interference with other medical devices, on
      the other hand they could improve the well-being, job satisfaction, productivity
      and decrease stress in nurse population. CONCLUSIONS: There are potential
      benefits of the smartphone use, but the smartphone misuse could have negative
      consequences on the quality care and patient' safety due to nurses' distraction
      and interruptions. For this reason, nurses should be careful when they use their
      smartphone for no work-related activities.

PMID- 28763185
TI  - The role of locally-designed organizational artifacts in supporting nurses' work:
      an ethnographic study on the wards
AB  - INTRODUCTION: This paper aims to describe how nurses' planning and coordination
      work is performed through the use of locally designed tools (i.e., diaries,
      planners, reminders, and organizers). These tools are investigated as the
      materialization of organizational work, thus offering a complementary perspective
      on nursing practice to that proposed by the professional mandate and supported by
      official artifacts in use. METHOD: Ethnographic study. RESULTS: By analyzing
      locally designed artifacts, the rationale that enables nurses to make the flow of
      activities work is highlighted and explained. Evidence is provided by a
      description of how nurses' tacit knowledge is reified and embedded into objects
      produced by the nurses themselves. Implications for the design of digital systems
      supporting nursing practice are discussed. CONCLUSION: The analysis of these
      artifacts has allowed an understanding of practices used by the nurses to manage
      the workflow in the wards.

PMID- 28763187
TI  - Nanoparticle Shape Influences the Magnetic Response of Ferro-Colloids.
AB  - The interesting magnetic response of conventional ferro-colloid has proved
      extremely useful in a wide range of technical applications. Furthermore, the use
      of nano/micro- sized magnetic particles has proliferated cutting-edge medical
      research, such as drug targeting and hyperthermia. In order to diversify and
      improve the application of such systems, new avenues of functionality must be
      explored. Current efforts focus on incorporating directional interactions that
      are surplus to the intrinsic magnetic one. This additional directionality can be
      conveniently introduced by considering systems composed of magnetic particles of
      different shapes. Here we present a combined analytical and simulation study of
      permanently magnetized dipolar superball particles; a geometry that closely
      resembles magnetic cubes synthesized in experiments. We have focused on
      determining the initial magnetic susceptibility of these particles in dilute
      suspensions, seeking to quantify the effect of the superball shape parameter on
      the system response. In turn, we linked the computed susceptibilities to the
      system microstructure by analyzing cluster composition using a connectivity
      network analysis. Our study has shown that by increasing the shape parameter of
      these superball particles, one can alter the outcome of self-assembly processes,
      leading to the observation of an unanticipated decrease in the initial static
      magnetic susceptibility.

PMID- 28763188
TI  - A Tug-of-War Mechanism for Pattern Formation in a Genetic Network.
AB  - Synthesizing spatial patterns with genetic networks is an ongoing challenge in
      synthetic biology. A successful demonstration of pattern formation would imply a
      better understanding of systems in the natural world and advance applications in
      synthetic biology. In developmental systems, transient patterning may suffice in
      order to imprint instructions for long-term development. In this paper we show
      that transient but persistent patterns can emerge from a realizable synthetic
      gene network based on a toggle switch. We show that a bistable system
      incorporating diffusible molecules can generate patterns that resemble Turing
      patterns but are distinctly different in the underlying mechanism: diffusion of
      mutually inhibiting molecules creates a prolonged "tug-of-war" between patches of
      cells at opposing bistable states. The patterns are transient but longer
      wavelength patterns persist for extended periods of time. Analysis of a
      representative small scale model implies the eigenvalues of the persistent modes
      are just above the threshold of stability. The results are verified through
      simulation of biologically relevant models.

PMID- 28763189
TI  - Understanding Variations in Circularly Polarized Photoluminescence in Monolayer
      Transition Metal Dichalcogenides.
AB  - Monolayer transition metal dichalcogenides are promising materials for
      valleytronic operations. They exhibit two inequivalent valleys in the Brillouin
      zone, and the valley populations can be directly controlled and determined using
      circularly polarized optical excitation and emission. The photoluminescence
      polarization reflects the ratio of the two valley populations. A wide range of
      values for the degree of circularly polarized emission, Pcirc, has been reported
      for monolayer WS2, although the reasons for the disparity are unclear. Here, we
      optically populate one valley and measure Pcirc to explore the valley population
      dynamics at room temperature in a large number of monolayer WS2 samples
      synthesized via chemical vapor deposition. Under resonant excitation, Pcirc
      ranges from 2 to 32%, and we observe a pronounced inverse relationship between
      photoluminescence (PL) intensity and Pcirc. High-quality samples exhibiting
      strong PL and long exciton relaxation time exhibit a low degree of valley
      polarization, and vice versa. This behavior is also demonstrated in monolayer
      WSe2 samples and transferred WS2, indicating that this correlation may be more
      generally observed and account for the wide variations reported for Pcirc. Time
      resolved PL provides insight into the role of radiative and nonradiative
      contributions to the observed polarization. Short nonradiative lifetimes result
      in a higher measured polarization by limiting opportunity for depolarizing
      scattering events.

PMID- 28763190
TI  - An Interlaboratory Evaluation of Drift Tube Ion Mobility-Mass Spectrometry
      Collision Cross Section Measurements.
AB  - Collision cross section (CCS) measurements resulting from ion mobility-mass
      spectrometry (IM-MS) experiments provide a promising orthogonal dimension of
      structural information in MS-based analytical separations. As with any molecular
      identifier, interlaboratory standardization must precede broad range integration
      into analytical workflows. In this study, we present a reference drift tube ion
      mobility mass spectrometer (DTIM-MS) where improvements on the measurement
      accuracy of experimental parameters influencing IM separations provide
      standardized drift tube, nitrogen CCS values (DTCCSN2) for over 120 unique ion
      species with the lowest measurement uncertainty to date. The reproducibility of
      these DTCCSN2 values are evaluated across three additional laboratories on a
      commercially available DTIM-MS instrument. The traditional stepped field CCS
      method performs with a relative standard deviation (RSD) of 0.29% for all ion
      species across the three additional laboratories. The calibrated single field CCS
      method, which is compatible with a wide range of chromatographic inlet systems,
      performs with an average, absolute bias of 0.54% to the standardized stepped
      field DTCCSN2 values on the reference system. The low RSD and biases observed in
      this interlaboratory study illustrate the potential of DTIM-MS for providing a
      molecular identifier for a broad range of discovery based analyses.

PMID- 28763192
TI  - Enhancing the Affinity of Anti-Human alpha-Thrombin 15-mer DNA Aptamer and Anti
      Immunoglobulin E Aptamer by PolyT Extension.
AB  - Aptamer affinity capillary electrophoresis-laser-induced fluorescence (CE-LIF)
      for protein detection takes advantage of aptamers for their ease of synthesis and
      labeling, small size, and having many negative charges. Its success relies on the
      high binding affinity of aptamers. One 15-mer DNA aptamer (5'-GGT TGG TGT GGT TGG
      3', Apt15) shows desirable specificity for human alpha-thrombin, an important
      enzyme with multiple functions in blood. However, Apt15 has weak binding
      affinity, and the use of Apt15 in affinity CE-LIF analysis remains challenging.
      Here we reported that extension of Apt15 at the 3'-end with a polyT tail having
      length of 18 T or longer significantly enhanced its affinity and enabled a well
      isolated and stable peak for thrombin-aptamer complex in affinity CE. It was
      likely that the improvement of binding affinity resulted from double binding, an
      additional interaction of the polyT tail with thrombin in addition to the Apt15
      section binding to thrombin. With dye-labeled Apt15 having a T25 tail, we
      achieved detection of thrombin at concentrations as low as 0.1 nM by affinity CE
      LIF. This aptamer probe specifically bound to human alpha-thrombin, showing
      negligible affinity for human beta- and gamma-thrombin, which are proteolyzed
      derivatives of human alpha alpha-thrombin and share similar structure. This
      strategy of adding a polyT extension also enhanced the binding affinity of anti
      immunoglobulin E aptamer in CE-LIF analysis, showing that the affinity
      enhancement approach is not limited to the thrombin-binding aptamer and has
      potential for more applications in bioanalysis.

PMID- 28763191
TI  - Nanoporous Immunoprotective Device for Stem-Cell-Derived beta-Cell Replacement
      Therapy.
AB  - Encapsulation of human embryonic stem-cell-differentiated beta cell clusters (hES
      betaC) holds great promise for cell replacement therapy for the treatment of
      diabetics without the need for chronic systemic immune suppression. Here, we
      demonstrate a nanoporous immunoprotective polymer thin film cell encapsulation
      device that can exclude immune molecules while allowing exchange of oxygen and
      nutrients necessary for in vitro and in vivo stem cell viability and function.
      Biocompatibility studies show the device promotes neovascular formation with
      limited foreign body response in vivo. The device also successfully prevented
      teratoma escape into the peritoneal cavity of mice. Long-term animal studies
      demonstrate evidence of engraftment, viability, and function of cells
      encapsulated in the device after 6 months. Finally, in vivo study confirms that
      the device was able to effectively immuno-isolate cells from the host immune
      system.

PMID- 28763193
TI  - Peptide-Membrane Interaction between Targeting and Lysis.
AB  - Certain cationic peptides interact with biological membranes. These often-complex
      interactions can result in peptide targeting to the membrane, or in membrane
      permeation, rupture, and cell lysis. We investigated the relationship between the
      structural features of membrane-active peptides and these effects, to better
      understand these processes. To this end, we employed a computational method for
      morphing a membranolytic antimicrobial peptide into a nonmembranolytic
      mitochondrial targeting peptide by "directed simulated evolution." The results
      obtained demonstrate that superficially subtle sequence modifications can
      strongly affect the peptides' membranolytic and membrane-targeting abilities.
      Spectroscopic and computational analyses suggest that N- and C-terminal
      structural flexibility plays a crucial role in determining the mode of peptide
      membrane interaction.

PMID- 28763194
TI  - Enhanced Visualization of Hematoxylin and Eosin Stained Pathological
      Characteristics by Phasor Approach.
AB  - The phasor approach to fluorescence lifetime imaging microscopy (FLIM) is used to
      identify different types of tissues from hematoxylin and eosin (H&E) stained
      basal cell carcinoma (BCC) sections. The results suggest that working directly on
      the phasor space with the clustering assignment achieves immunofluorescence like
      simultaneous five or six-color imaging by using multiplexed fluorescence
      lifetimes of H&E. The phase approach is of particular effectiveness for enhanced
      visualization of the abnormal morphology of a suspected nidus. Moreover, the
      phasor approach to H&E FLIM data can determine the actual paths or the
      infiltrating trajectories of basophils and immune cells associated with the
      preneoplastic or neoplastic skin lesions. The integration of the phasor approach
      with routine histology proved its available value for skin cancer prevention and
      early detection. We therefore believe that the phasor analysis of H&E tissue
      sections is an enhanced visualization tool with the potential to simplify the
      preparation process of special staining and serve as color contrast aided imaging
      in clinical pathological examination.

PMID- 28763195
TI  - Immunohistochemistry Microarrays.
AB  - Immunohistochemistry (IHC) on tissue sections is widely used for quantifying the
      expression patterns of proteins and is part of the standard of care for cancer
      diagnosis and prognosis, but is limited to staining a single protein per tissue.
      Tissue microarray and microfluidics staining methods have emerged as powerful
      high throughput techniques, but they either only permit the analysis of a single
      protein per slide or require complex instrumentation and expertise while only
      staining isolated areas. Here, we introduce IHC microarrays (IHCMUA) for
      multiplexed staining of intact tissues with preserved histological and spatial
      information. Droplets of a dextran solution containing antibodies were prespotted
      on a slide and snapped onto a preprocessed formalin-fixed, paraffin-embedded
      (FFPE) tissue section soaked in a polyethylene glycol solution. The antibodies
      are confined within the dextran droplets and locally stain the tissue below with
      a contrast similar to the one obtained by conventional IHC. The microarray of
      antibody droplets can be prespotted on a slide and stored, thus neither the
      preparation of the antibody solutions nor a sophisticated microarray spotter is
      needed. Sampling considerations with IHCMUA were evaluated by taking three
      tissues with varying levels of cancer cells. A multiplex IHCMUA with 180 spots
      targeting 8 cancer proteins was performed on a breast cancer tissue section to
      illustrate the potential of this method. This work opens the avenue of applying
      microarray technologies for conducting IHC on intact tissue slices and has great
      potential to be used in the discovery and validation of tissue biomarkers in
      human tumors.

PMID- 28763196
TI  - Lithium-Ion Insertion Properties of Solution-Exfoliated Germanane.
AB  - The high theoretical energy density of alloyed lithium and germanium (Li15Ge4),
      1384 mAh/g, makes germanium a promising anode material for lithium-ion batteries.
      However, common alloy anode architectures suffer from long-term instability upon
      repetitive charge-discharge cycles that arise from stress-induced degradation
      upon lithiation (volume expansion >300%). Here, we explore the use of the two
      dimensional nanosheet structure of germanane to mitigate stress from high volume
      expansion and present a facile method for producing stable single-to-multisheet
      dispersions of pure germanane. Purity and degree of exfoliation were assessed
      with scanning electron microscopy, transmission electron microscopy, and Raman
      spectroscopy. We measured representative germanane battery electrodes to have a
      reversible Li-ion capacity of 1108 mAh/g when cycled between 0.1 and 2 V vs
      Li/Li+. These results indicate germanane anodes are capable of near-theoretical
      maximum energy storage, perform well at high cycling rates, and can maintain
      capacity over 100 cycles.

PMID- 28763197
TI  - Cyclodextrin/Paclitaxel Dimer Assembling Vesicles: Reversible Morphology
      Transition and Cargo Delivery.
AB  - Here, we developed stable supramolecular binary vesicles on the basis of the host
      guest interaction between beta-cyclodextrins (beta-CDs) and paclitaxel (PTX)
      dimer. The inclusion complexation between PTX dimer and beta-CDs in water was
      studied by proton nuclear magnetic resonance spectroscopy and two-dimensional
      rotating-frame Overhauser effect spectroscopy. The resulting inclusion complex
      was amphiphilic and could self-assemble into vesicles with average diameter of
      230 nm. The vesicles could evolve to nanoparticles (NPs) by adding competitive
      binding guest amantadine hydrochloride or by digesting beta-CDs through alpha
      amylase. Moreover, this process was reversible, and the NPs could also transform
      to vesicles by adding enough beta-CDs again. The obtained hollow supramolecular
      vesicles were further explored to load hydrophilic dye indocyanine green molecule
      or hydrophobic anticancer drug doxorobicin for their controlled release under
      external stimulus. This work provides a new strategy for the design of
      supramolecular systems by using prodrug as building blocks.

PMID- 28763198
TI  - Fundamental Design Principles for Transcription-Factor-Based Metabolite
      Biosensors.
AB  - Metabolite biosensors are central to current efforts toward precision engineering
      of metabolism. Although most research has focused on building new biosensors,
      their tunability remains poorly understood and is fundamental for their broad
      applicability. Here we asked how genetic modifications shape the dose-response
      curve of biosensors based on metabolite-responsive transcription factors. Using
      the lac system in Escherichia coli as a model system, we built promoter libraries
      with variable operator sites that reveal interdependencies between biosensor
      dynamic range and response threshold. We developed a phenomenological theory to
      quantify such design constraints in biosensors with various architectures and
      tunable parameters. Our theory reveals a maximal achievable dynamic range and
      exposes tunable parameters for orthogonal control of dynamic range and response
      threshold. Our work sheds light on fundamental limits of synthetic biology
      designs and provides quantitative guidelines for biosensor design in applications
      such as dynamic pathway control, strain optimization, and real-time monitoring of
      metabolism.

PMID- 28763200
TI  - Electrochemical Approach for Analyzing Electrolyte Transport Properties and Their
      Effect on Protonic Ceramic Fuel Cell Performance.
AB  - The design and development of highly conductive materials with wide electrolytic
      domain boundaries are among the most promising means of enabling solid oxide fuel
      cells (SOFCs) to demonstrate outstanding performance across low- and intermediate
      temperature ranges. While reducing the thickness of the electrolyte is an
      extensively studied means for diminishing the total resistance of SOFCs,
      approaches involving an improvement in the transport behavior of the electrolyte
      membranes have been less-investigated. In the present work, a strategy for
      analyzing the electrolyte properties and their effect on SOFC output
      characteristics is proposed. To this purpose, a SOFC based on a recently
      developed BaCe0.5Zr0.3Dy0.2O3-delta proton-conducting ceramic material was
      fabricated and tested. The basis of the strategy consists of the use of
      traditional SOFC testing techniques combined with the current interruption method
      and electromotive force measurements with a modified polarization-correction
      assessment. This allows one to determine simultaneously such important parameters
      as maximal power density; ohmic and polarization resistances; average ion
      transport numbers; and total, ionic, and electronic film conductivities and their
      activation energies. The proposed experimental procedure is expected to expand
      both fundamental and applied basics that could be further adopted to improve the
      technology of electrochemical devices based on proton-conducting electrolytes.

PMID- 28763199
TI  - Specific Histidine Residues Confer Histatin Peptides with Copper-Dependent
      Activity against Candida albicans.
AB  - The histidine-rich salivary peptides of the histatin family are known to bind
      copper (Cu) and other metal ions in vitro; however, the details of these
      interactions are poorly understood, and their implications for in vivo antifungal
      activity have not been established. Here, we show that the availability of Cu
      during exposure of Candida albicans to histatin-5 (Hist-5) modulates its
      antifungal activity. Antifungal susceptibility testing revealed that co-treatment
      of Hist-5 with Cu improved the EC50 from ~5 to ~1 MUM, whereas co-treatment with
      a high-affinity Cu-specific chelator abrogated antifungal activity.
      Spectrophotometric titrations revealed two previously unrecognized Cu(I)-binding
      sites with apparent Kd values at pH 7.4, ~20 nM, and confirmed a high-affinity
      Cu(II)-binding site at the Hist-5 N-terminus with an apparent Kd of ~8 pM.
      Evaluation of a series of His-to-Ala full-length and truncated Hist-5 peptides
      identified adjacent His residues (bis-His) as critical anchors for Cu(I) binding,
      with the presence of a third ligand revealed by X-ray absorption spectroscopy. On
      their own, the truncated peptides were ineffective at inhibiting the growth of C.
      albicans, but treatment with supplemental Cu resulted in EC50 values down to ~5
      MUM, approaching that of full-length Hist-5. The efficacy of the peptides
      depended on an intact bis-His site and correlated with Cu(I) affinity. Together,
      these results establish new structure-function relationships linking specific
      histidine residues with Cu binding affinity and antifungal activity and provide
      further evidence of the involvement of metals in modulating the biological
      activity of these antifungal peptides.

PMID- 28763201
TI  - Tracking Reactive Water and Hydrogen-Bonding Networks in Photosynthetic Oxygen
      Evolution.
AB  - In oxygenic photosynthesis, photosystem II (PSII) converts water to molecular
      oxygen through four photodriven oxidation events at a Mn4CaO5 cluster. A
      tyrosine, YZ (Y161 in the D1 polypeptide), transfers oxidizing equivalents from
      an oxidized, primary chlorophyll donor to the metal center. Calcium or its
      analogue, strontium, is required for activity. The Mn4CaO5 cluster and YZ are
      predicted to be hydrogen bonded in a water-containing network, which involves
      amide carbonyl groups, amino acid side chains, and water. This hydrogen-bonded
      network includes amino acid residues in intrinsic and extrinsic subunits. One of
      the extrinsic subunits, PsbO, is intrinsically disordered. This extensive (35 A)
      network may be essential in facilitating proton release from substrate water.
      While it is known that some proteins employ internal water molecules to catalyze
      reactions, there are relatively few methods that can be used to study the role of
      water. In this Account, we review spectroscopic evidence from our group
      supporting the conclusion that the PSII hydrogen-bonding network is dynamic and
      that water in the network plays a direct role in catalysis. Two approaches,
      transient electron paramagnetic resonance (EPR) and reaction-induced FT-IR (RIFT
      IR) spectroscopies, were used. The EPR experiments focused on the decay kinetics
      of YZ* via recombination at 190 K and the solvent isotope, pH, and calcium
      dependence of these kinetics. The RIFT-IR experiments focused on shifts in amide
      carbonyl frequencies, induced by photo-oxidation of the metal cluster, and on the
      isotope-based assignment of bands to internal, small protonated water clusters at
      190, 263, and 283 K. To conduct these experiments, PSII was prepared in selected
      steps along the catalytic pathway, the Sn state cycle (n = 0-4). This cycle
      ultimately generates oxygen. In the EPR studies, S-state dependent changes were
      observed in the YZ* lifetime and in its solvent isotope effect. The YZ* lifetime
      depended on the presence of calcium at pH 7.5, but not at pH 6.0, suggesting a
      two-donor model for PCET. At pH 6.0 or 7.5, barium and ammonia both slowed the
      rate of YZ* recombination, consistent with disruption of the hydrogen-bonding
      network. In the RIFT-IR studies of the S state transitions, infrared bands
      associated with the transient protonation and deprotonation of internal waters
      were identified by D2O and H218O labeling. The infrared bands of these protonated
      water clusters, Wn+ (or nH2O(H3O)+, n = 5-6), exhibited flash dependence and were
      produced during the S1 to S2 and S3 to S0 transitions. Calcium dependence was
      observed at pH 7.5, but not at pH 6.0. S-state induced shifts were observed in
      amide C?O frequencies during the S1 to S2 transition and attributed to
      alterations in hydrogen bonding, based on ammonia sensitivity. In addition,
      isotope editing of the extrinsic subunit, PsbO, established that amide
      vibrational bands of this lumenal subunit respond to the S state transitions and
      that PsbO is a structural template for the reaction center. Taken together, these
      spectroscopic results support the hypothesis that proton transfer networks,
      extending from YZ to PsbO, play a functional and dynamic role in photosynthetic
      oxygen evolution.

PMID- 28763202
TI  - Paleo-ecotoxicology: What Can Lake Sediments Tell Us about Ecosystem Responses to
      Environmental Pollutants?
AB  - The development of effective risk reduction strategies for aquatic pollutants
      requires a comprehensive understanding of toxic impacts on ecosystems. Classical
      toxicological studies are effective for characterizing pollutant impacts on biota
      in a controlled, simplified environment. Nonetheless, it is well-acknowledged
      that predictions based on the results of these studies must be tested over the
      long-term in a natural ecosystem setting to account for increased complexity and
      multiple stressors. Paleolimnology (the study of lake sediment cores to
      reconstruct environmental change) can address many key knowledge gaps. When used
      as part of a weight-of-evidence framework with more traditional approaches in
      ecotoxicology, it can facilitate rapid advances in our understanding of the
      chronic effects of pollutants on ecosystems in an environmentally realistic,
      multistressor context. Paleolimnology played a central role in the Acid Rain
      debates, as it was instrumental in demonstrating industrial emissions caused
      acidification of lakes and associated ecosystem-wide impacts. "Resurrection
      Ecology" (hatching dormant resting eggs deposited in the past) records
      evolutionary responses of populations to chronic pollutant exposure. With recent
      technological advances (e.g., geochemistry, genomic approaches), combined with an
      emerging paleo-ecotoxicological framework that leverages strengths across
      multiple disciplines, paleolimnology will continue to provide valuable insights
      into the most pressing questions in ecotoxicology.

PMID- 28763203
TI  - Shallow Gas Migration along Hydrocarbon Wells-An Unconsidered, Anthropogenic
      Source of Biogenic Methane in the North Sea.
AB  - Shallow gas migration along hydrocarbon wells constitutes a potential methane
      emission pathway that currently is not recognized in any regulatory framework or
      greenhouse gas inventory. Recently, the first methane emission measurements at
      three abandoned offshore wells in the Central North Sea (CNS) were conducted
      showing that considerable amounts of biogenic methane originating from shallow
      gas accumulations in the overburden of deep reservoirs were released by the
      boreholes. Here, we identify numerous wells poking through shallow gas pockets in
      3-D seismic data of the CNS indicating that about one-third of the wells may
      leak, potentially releasing a total of 3-17 kt of methane per year into the North
      Sea. This poses a significant contribution to the North Sea methane budget. A
      large fraction of this gas (~42%) may reach the atmosphere via direct bubble
      transport (0-2 kt yr-1) and via diffusive exchange of methane dissolving in the
      surface mixed layer (1-5 kt yr-1), as indicated by numerical modeling. In the
      North Sea and in other hydrocarbon-prolific provinces of the world shallow gas
      pockets are frequently observed in the sedimentary overburden and aggregate
      leakages along the numerous wells drilled in those areas may be significant.

PMID- 28763204
TI  - Effect of Kumatakenin Isolated From Cloves on the Apoptosis of Cancer Cells and
      the Alternative Activation of Tumor-Associated Macrophages.
AB  - The flower bud of Syzygium aromaticum (clove) has been used for centuries as a
      spice and herbal medicine. The biological activities of kumatakenin, a flavonoid
      that has recently been isolated from cloves, are poorly characterized. In the
      present study, the anticancer effects of kumatakenin in human ovarian cancer
      cells and tumor-associated macrophages (TAMs) were investigated. We found that
      kumatakenin exhibited significant cytotoxic activity in human ovarian cancer
      cells, SKOV3 and A2780. A propidium iodide and Annexin V-FITC staining assay
      showed that kumatakenin induces apoptosis in ovarian cancer cells. Kumatakenin
      treatment increased the activity of caspase-3, -8, and -9, and caspase inhibitors
      attenuated kumatakenin-induced SKOV3 cell death. In addition, kumatakenin was
      found to reduce the expressions of MCP-1 and RANTES, which are major determinants
      of macrophage recruitment at tumor sites in ovarian cancer cells. Moreover,
      kumatakenin inhibited the expression of M2 markers and cancer-promoting factors,
      including IL-10, MMP-2/-9, and VEGF, in macrophages stimulated by the ovarian
      cancer cells. In conclusion, these results suggest that kumatakenin shows
      anticancer activities by inducing apoptosis of ovarian cancer cells and
      inhibiting the alternative activation of TAM.

PMID- 28763206
TI  - Symmetry-Adapted Ro-vibrational Basis Functions for Variational Nuclear Motion
      Calculations: TROVE Approach.
AB  - We present a general, numerically motivated approach to the construction of
      symmetry-adapted basis functions for solving ro-vibrational Schrodinger
      equations. The approach is based on the property of the Hamiltonian operator to
      commute with the complete set of symmetry operators and, hence, to reflect the
      symmetry of the system. The symmetry-adapted ro-vibrational basis set is
      constructed numerically by solving a set of reduced vibrational eigenvalue
      problems. In order to assign the irreducible representations associated with
      these eigenfunctions, their symmetry properties are probed on a grid of molecular
      geometries with the corresponding symmetry operations. The transformation
      matrices are reconstructed by solving overdetermined systems of linear equations
      related to the transformation properties of the corresponding wave functions on
      the grid. Our method is implemented in the variational approach TROVE and has
      been successfully applied to many problems covering the most important molecular
      symmetry groups. Several examples are used to illustrate the procedure, which can
      be easily applied to different types of coordinates, basis sets, and molecular
      systems.

PMID- 28763205
TI  - Tandem Palladium and Isothiourea Relay Catalysis: Enantioselective Synthesis of
      alpha-Amino Acid Derivatives via Allylic Amination and [2,3]-Sigmatropic
      Rearrangement.
AB  - A tandem relay catalytic protocol using both Pd and isothiourea catalysis has
      been developed for the enantioselective synthesis of alpha-amino acid derivatives
      containing two stereogenic centers from readily accessible N,N-disubstituted
      glycine aryl esters and allylic phosphates. The optimized process uses a bench
      stable succinimide-based Pd precatalyst (FurCat) to promote Pd-catalyzed allylic
      ammonium salt generation from the allylic phosphate and the glycine aryl ester.
      Subsequent in situ enantioselective [2,3]-sigmatropic rearrangement catalyzed by
      the isothiourea benzotetramisole forms syn-alpha-amino acid derivatives with high
      diastereo- and enantioselectivity. This methodology is most effective using 4
      nitrophenylglycine esters and tolerates a variety of substituted cinnamic and
      styrenyl allylic ethyl phosphates. The use of challenging unsymmetrical N-allyl-N
      methylglycine esters is also tolerated under the catalytic relay conditions
      without compromising stereoselectivity.

PMID- 28763207
TI  - Inhibition of Human Enhancer of Zeste Homolog 2 with Tambjamine Analogs.
AB  - Combining computational modeling, de novo compound synthesis, and in vitro and
      cellular assays, we have performed an inhibition study against the enhancer of
      zeste homolog 2 (EZH2) histone-lysine N-methyltransferase. This enzyme is an
      important catalytic component of the PRC2 complex whose alterations have been
      associated with different cancers. We introduce here several tambjamine-inspired
      derivatives with low micromolar in vitro activity that produce a significant
      decrease in histone 3 trimethylation levels in cancer cells. We demonstrate
      binding at the methyl transfer active site, showing, in addition, that the EZH2
      isolated crystal structure is capable of being used in molecular screening
      studies. Altogether, this work provides a successful molecular model that will
      help in the identification of new specific EZH2 inhibitors and identify a novel
      class of tambjamine-derived EZH2 inhibitors with promising activities for their
      use in cancer treatment.

PMID- 28763208
TI  - Theoretical Study and Design of Phosphorescent Cyclometalated (C?C*)PtII(acac)
      Complexes: The Substituent Effect Controls the Radiative and Nonradiative Decay
      Processes.
AB  - Density functional theory (DFT) and time-dependent DFT calculations were
      performed to evaluate the influence of substituent effect of (1) R = 4-Me, (2) R
      = 4-OMe, and (3) R = 2,3-OC6H4 on the phenyl ring of (C?C*)PtII(acac) (C?C* =
      phenylimidazole, acac = acetylacetone), respectively, on absorption and
      phosphorescent spectra properties, as well as the radiative and nonradiative
      processes. We found that emissions of complexes 2 and 3 originate from the Kasha
      like T1 state, whereas that of complex 1 originates from non-Kasha T2 state.
      Compared with the emission of complex 1, the emission peaks of 2 and 3 are red
      shifted, which is attributed to p-pi and pi-pi conjugation effects resulting from
      the electron-donating groups -OCH3 and -OC6H4 with ligand C?C*, respectively. The
      radiative rate constants (kappar) of 2 and 3 are larger than that of 1, namely,
      kappar(1) < kappar(2) < kappar(3), indicating that kappar can be efficiently
      increased by enlarging pi-conjugation at the main ligand of (C?C*)PtII(acac),
      which can cause the increase of spin-orbit coupling (SOC) matrix elements. At the
      same time, the activation energy barriers for the rate-limiting step can be
      largely raised accompanied by enlarging the ability of electron-donation of the
      substituent group at the main ligand of (C?C*)PtII(acac), which can cause the
      decrease of the nonradiative rate constant (kappanr), namely, kappanr(1) >
      kappanr(2) > kappanr(3). According to PhiP = kappar/(kappar + kappanr), the
      quantum yields should have the sequence PhiP(1) < PhiP(2) < PhiP(3), which is in
      accordance with the experiment. In addition, to guide experimental synthesis of
      highly efficient (C?C*)PtII(acac), a new complex 4 through extending the pi
      conjugation in the C?C* ligand of (C?C*)PtII(acac) was theoretically designed,
      which has a larger quantum yield than 1-3.

PMID- 28763209
TI  - Hydrolysis of Ammonia-Borane over Ni/ZIF-8 Nanocatalyst: High Efficiency,
      Mechanism, and Controlled Hydrogen Release.
AB  - Non-noble metal nanoparticles are notoriously difficult to prepare and stabilize
      with appropriate dispersion, which in turn severely limits their catalytic
      functions. Here, using zeolitic imidazolate framework (ZIF-8) as MOF template,
      catalytically remarkably efficient ligand-free first-row late transition-metal
      nanoparticles are prepared and compared. Upon scrutiny of the catalytic
      principles in the hydrolysis of ammonia-borane, the highest total turnover
      frequency among these first-row late transition metals is achieved for the
      templated Ni nanoparticles with 85.7 molH2 molcat-1 min-1 at room temperature,
      which overtakes performances of previous non-noble metal nanoparticles systems,
      and is even better than some noble metal nanoparticles systems. Mechanistic
      studies especially using kinetic isotope effects show that cleavage by oxidative
      addition of an O-H bond in H2O is the rate-determining step in this reaction.
      Inspired by these mechanistic studies, an attractive and effective "on-off"
      control of hydrogen production is further proposed.

PMID- 28763210
TI  - Effects of Static Correlation between Spin Centers in Multicenter Transition
      Metal Complexes.
AB  - Multicenter transition metal complexes are the key moieties of many processes in
      chemistry, biochemistry, and materials science such as in the active sites of
      enzymes, molecular catalysts, and biological electron carriers. Their electronic
      structure, often characterized by high-spin-polarized metal sites, is a challenge
      for theoretical chemists because of their high degree of dynamical and static
      correlation. Static correlation is necessary both for the appropriate description
      of the metal-ligand bonding and for a correct description of the multideterminant
      character arising from the magnetic interactions between spin centers. Density
      functional theory (DFT) is usually applied using a single-determinant broken
      symmetry state that is lacking the correct spin symmetry when the ground state
      has total low-spin character. To alleviate this drawback, we use the extended
      broken-symmetry (EBS) approach to derive approximate ground-state energies and,
      for the first time, forces for the correctly symmetric ground state of an
      arbitrary number of spin centers within the framework of the Heisenberg-Dirac-van
      Vleck Hamiltonian. Remarkably, the proposed procedure supplies relaxed geometries
      that are fully consistent with the calculated J-coupling constants. We apply the
      method to investigate the relaxed geometrical structure of the low-spin ground
      state of iron-sulfur clusters with two, three, and four iron centers. We observed
      significant differences in both geometrical parameters and coupling constant J
      between the symmetrized ground state, the high-spin, and the broken-symmetry
      optimized structures. These changes are often comparable with the differences
      observed by using different functionals, and the use of EBS always improves the
      description of the studied systems. It will be therefore important to include it
      in any DFT attempt to quantitatively describe multicenter transition metal
      complexes in the future.

PMID- 28763211
TI  - Ligand Design toward Multifunctional Substrate Reductive Transformations.
AB  - The synthesis of bis(N1-phenyl-5-hydroxypyrazol-3-yl)pyridines ("L") is
      described, and these are silylated to achieve analogues ("Si2L") without the
      variable of the hydroxyl proton mobility. One hydroxyl example is characterized
      in its bis-pincer iron(II) complex, which shows every OH proton involved in
      hydrogen bonding. The steric bulk of the silylated N-phenyl-substituted ligands
      allows the synthesis and characterization of paramagnetic (Si2L)FeCl2 complexes,
      and one of these is reduced, under CO, to give the diamagnetic (Si2L)Fe(CO)2
      species. Structural comparison and density functional theory calculations of the
      dichloride and dicarbonyl species show that much, but not all, of the reduction
      occurs at both the ligand pyridine and pyrazole rings, and thus this ligand type
      is more resistant to reduction than the simpler bis(iminopyridines). The OSiR3
      substituent offers a useful diagnostic of reduction at pyrazole via the degree of
      pi-donation to pyrazole by the oxygen lone pairs, and the stereoelectronic
      features of the NPh moiety are analyzed. The X-ray photoelectron spectroscopy
      binding energies of both iron and nitrogen are analyzed to show details of the
      locus of reduction.

PMID- 28763212
TI  - Cafestol, a Bioactive Substance in Coffee, Has Antidiabetic Properties in KKAy
      Mice.
AB  - Daily coffee consumption is inversely associated with risk of type-2 diabetes
      (T2D). Cafestol, a bioactive substance in coffee, increases glucose-stimulated
      insulin secretion in vitro and increases glucose uptake in human skeletal muscle
      cells. We hypothesized that cafestol can postpone development of T2D in KKAy
      mice. Forty-seven male KKAy mice were randomized to consume chow supplemented
      daily with either 1.1 (high), 0.4 (low), or 0 (control) mg of cafestol for 10
      weeks. We collected blood samples for fasting glucose, glucagon, and insulin as
      well as liver, muscle, and fat tissues for gene expression analysis. We isolated
      islets of Langerhans and measured insulin secretory capacity. After 10 weeks of
      intervention, fasting plasma glucose was 28-30% lower in cafestol groups compared
      with the control group (p < 0.01). Fasting glucagon was 20% lower and insulin
      sensitivity improved by 42% in the high-cafestol group (p < 0.05). Cafestol
      increased insulin secretion from isolated islets by 75-87% compared to the
      control group (p < 0.001). Our results show that cafestol possesses antidiabetic
      properties in KKAy mice. Consequently, cafestol may contribute to the reduced
      risk of developing T2D in coffee consumers and has a potential role as an
      antidiabetic drug.

PMID- 28763213
TI  - Novel 3-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indole-Based Multifunctional Ligands
      with Antipsychotic-Like, Mood-Modulating, and Procognitive Activity.
AB  - The most troublesome aspects of behavioral and psychological symptoms of dementia
      (BPSD) are nowadays addressed by antidepressant, anxiolytic, and antipsychotic
      drugs, often administered off-label. Considering their modest effectiveness in
      dementia patients, the increased risk of adverse events and cognitive decline,
      there is an unmet need for well-tolerated and effective therapy of BPSD. We
      designed and synthesized multifunctional ligands characterized in vitro as high
      affinity partial agonists of D2R, antagonists of 5-HT6R, and blockers of SERT.
      Moreover, the molecules activated 5-HT1AR and blocked 5-HT7R while having no
      relevant affinity for off-target M1R and hERG channel. Compound 16 (N-{2-[4-(5
      chloro-1H-indol-3-yl)-1,2,3,6-tetrahydropyridin-1-yl]ethyl}-3-methylbenzene-1
      sulfonamide) exhibited a broad antipsychotic-, antidepressant-, and anxiolytic
      like activity, not eliciting motor impairments in mice. Most importantly, 16
      showed memory-enhancing properties and it ameliorated memory deficits induced by
      scopolamine. The molecule outperformed most important comparators in selected
      tests, indicating its potential in the treatment of both cognitive and
      noncognitive (behavioral and psychological) symptoms of dementia.

PMID- 28763214
TI  - {[Si(SiMe3)3]2Ge9-SiMe2-(C6H4)-SiMe2-Ge9[Si(SiMe3)3]2K}-: The Connection of
      Metalloid Clusters via an Organic Linker.
AB  - The reaction of [(Hyp)2Ge9]2- (Hyp = Si(SiMe3)3) with ClSiMe2-C6H4-SiMe2Cl gives
      [K(THF)][(Hyp)2Ge9-SiMe2-C6H4-SiMe2-Ge9(Hyp)2K] K1 in 45% yield in the form of
      orange-red crystals. 1 is thereby the first compound where two Ge9(Hyp)2 clusters
      are bound together via a bridging ligand. 1 is stable in solution but cannot be
      transferred intact into the gas phase via electrospray ionization indicating a
      higher reactivity with respect to other metalloid Ge9R3 clusters. The arrangement
      of the nine germanium atoms within the two Ge9 units in 1 is unique for metalloid
      Ge9R3 clusters. Quantum chemical calculations further reveal an electronic
      interaction of the two Ge9 units in 1 via the bridging phenylene group.

PMID- 28763215
TI  - Tensor-Train Split-Operator Fourier Transform (TT-SOFT) Method: Multidimensional
      Nonadiabatic Quantum Dynamics.
AB  - We introduce the "tensor-train split-operator Fourier transform" (TT-SOFT) method
      for simulations of multidimensional nonadiabatic quantum dynamics. TT-SOFT is
      essentially the grid-based SOFT method implemented in dynamically adaptive tensor
      train representations. In the same spirit of all matrix product states, the
      tensor-train format enables the representation, propagation, and computation of
      observables of multidimensional wave functions in terms of the grid-based
      wavepacket tensor components, bypassing the need of actually computing the wave
      function in its full-rank tensor product grid space. We demonstrate the accuracy
      and efficiency of the TT-SOFT method as applied to propagation of 24-dimensional
      wave packets, describing the S1/S2 interconversion dynamics of pyrazine after UV
      photoexcitation to the S2 state. Our results show that the TT-SOFT method is a
      powerful computational approach for simulations of quantum dynamics of polyatomic
      systems since it avoids the exponential scaling problem of full-rank grid-based
      representations.

PMID- 28763216
TI  - Glucose and Mannose: A Link between Hydration and Sweetness.
AB  - Glucose and mannose have a different degree of sweetness, implying different
      affinity to the sweet taste receptor. While the receptor structure is still
      undefined, there are several geometrical models for their binding mechanism. A
      detailed study of the hydration structure of sugars with known degree of
      sweetness is bound to provide information on the accuracy of such models. Our
      neutron diffraction study on the hydration of glucose and mannose show that both
      alpha- and beta-glucose form strong hydrogen bonds with water, and that the
      steric hindrance of their first hydration shell matches the receptor geometrical
      model. The alpha-anomer of mannose has a similar, well-defined first hydration
      shell, but with fewer and weaker hydrogen bonds compared to glucose. Conversely,
      the hydration shell of beta-mannose (reported as bitter) does not match the
      receptor geometrical model. These findings suggest a link between the hydration
      shell of sugars and their degree of sweetness.

PMID- 28763217
TI  - Characterization of G4-G4 Crosstalk in the c-KIT Promoter Region.
AB  - The proximal promoter of c-KIT contains a peculiar domain that consists of three
      short G-rich sequences that are close together and can fold into noncanonical DNA
      secondary structures called G-quadruplexes (G4). Here, we focused on a sequence
      containing two consecutive G4 (kit2 and kit*). By electrophoretic, surface
      plasmon resonance, and spectroscopic techniques, we demonstrated that they retain
      the ability to fold into G4 upon being inserted into the extended sequence. Here,
      we highlighted the occurrence of crosstalk between the two forming units. This
      previously unexplored G4-G4 interaction modulates both the conformation and the
      stability of the overall arrangement of the c-KIT promoter. It is not supported
      by stacking of single nucleotides but refers to a G4-G4 interaction surface
      surrounded by a two-nucleotides loop that might represent a reliable
      unprecedented target for anticancer therapy.

PMID- 28763218
TI  - Total Synthesis of Terpenoids Employing a "Benzannulation of Carvone" Strategy:
      Synthesis of (-)-Crotogoudin.
AB  - Carvone is a sustainable and readily available starting material for organic
      synthesis. Herein, we present the syntheses of various natural product scaffolds
      that rely on a novel benzannulation involving the alpha-methyl group (C-10) of
      carvone to afford a versatile tetralin. The utility of our synthetic approach is
      highlighted by its application to a short synthesis of the ent-3,4-seco-atisane
      diterpenoid (-)-crotogoudin. The 13-step enantiospecific synthesis features a
      regioselective double oxidative dearomatization, a Diels-Alder cycloaddition with
      ethylene gas (to construct the bicyclo[2.2.2]octane framework), and a final acid
      mediated lactonization. The versatility of this benzannulation strategy is
      demonstrated by its utility in the preparation of the carbon skeleton of ent-3,4
      seco-abietane diterpenoids using an intramolecular oxidative dearomatization.

PMID- 28763219
TI  - Synthesis and Characterization of a Series of Bis-homoleptic Cycloruthenates with
      Terdentate Ligands as a Family of Panchromatic Dyes.
AB  - A series of six homoleptic bis-cyclometalated ruthenium complexes, Ru(N^N^C)2, is
      reported where N^N^C is a 6-(2,4-difluoro-3-R3-phenyl)-4-R2-4'-R1-2,2'-bipyridine
      with R3 = -H or -CF3 and R2 and R1 = -COOEt or -CF3. An effective synthesis of
      the ligands and the complexes is described. The UV-visible absorption studies
      demonstrate that these complexes are panchromatic dyes absorbing up to 900 nm.
      Importantly, the onset of absorption depends only on the substitution on the
      metalated phenyl, whereas the intensity of absorption throughout the spectra is a
      function of substituents on both the phenyl and the bipyridine moieties. The same
      trend is observed in electrochemistry as the redox gap depends only on the
      substitution on the metalated phenyl, whereas the oxidation and reduction
      potentials are a function of substituents on both the phenyl and the bipyridine
      moieties. Preliminary tests as sensitizer for dye-sensitized solar cells
      demonstrate that the number of anchoring groups on the dye has a major influence
      on the device efficiency.

PMID- 28763220
TI  - Time-Dependent Double-Hybrid Density Functionals with Spin-Component and Spin
      Opposite Scaling.
AB  - For the first time, we combine time-dependent double-hybrid density functional
      approximations (TD-DHDFAs) for the calculation of electronic excitation energies
      with the concepts of spin-component and spin-opposite scaling (SCS/SOS) of
      electron-pair contributions to their nonlocal correlation components. Different
      flavors of this idea, ranging from standard SCS parameters to fully fitted
      parameter sets, are presented and tested on six different parent DHDFAs. For
      cross-validation, we assess those methods on three benchmark sets that cover
      small- to medium-sized chromophores (up to 78 atoms) and different excitation
      types. For this purpose, we also introduce new CC3 reference values for the
      popular Gordon benchmark set that we recommend using in future studies. Our
      results confirm that already the (unscaled) parent TD-DHDFAs are accurate and
      outperform some wave function methods. Further introduction of SCS/SOS eliminates
      extreme outliers, reduces deviation spans from reference values by up to 0.5 eV,
      aligns the performance of the Tamm-Dancoff approximation (TDA) to that of full TD
      calculations, and also enables a more balanced description of different
      excitation types. The best-performing TD-based methods in our cross validation
      have mean absolute deviations as low as 0.14 eV compared to the time- and
      resource-intensive CC3 approach. A very important finding is that we also
      obtained SOS variants with excellent performance, contrary to wave function based
      methods. This opens a future pathway to highly efficient methods for the
      optimization of excited-state geometries, particularly when paired with computing
      strategies such as the Laplace transform. We recommend our SCS- and SOS-based
      variants for further testing and subsequent applications.

PMID- 28763222
TI  - Attraction between Opposing Planar Dipolar Polymer Brushes.
AB  - We use a field theory approach to study the effects of permanent dipoles on
      interpenetration and free energy changes as a function of distance between two
      identical planar polymer brushes. Melts (i.e., solvent-free) and solvated brushes
      made up of polymers grafted on nonadsorbing substrates are studied. In
      particular, the weak coupling limit of the dipolar interactions is considered,
      which leads to concentration-dependent pairwise interactions, and the effects of
      orientational order are neglected. It is predicted that a gradual increase in the
      dipole moment of the polymer segments can lead to attractive interactions between
      the brushes at intermediate separation distances. Because classical theory of
      polymer brushes based on the strong stretching limit (SSL) and the standard self
      consistent field theory (SCFT) simulations using the Flory's chi parameter always
      predicts repulsive interactions at all separations, our work highlights the
      importance of dipolar interactions in tailoring and accurately predicting forces
      between polar polymeric interfaces in contact with each other.

PMID- 28763223
TI  - Determination of the Absolute Configuration of Cyclic Amines with Bode's Chiral
      Hydroxamic Esters Using the Competing Enantioselective Conversion Method.
AB  - The competing enantioselective conversion (CEC) strategy has been extended to
      cyclic amines. The basis for the CEC approach is the use of two complementary,
      enantioselective reactions to determine the configuration of the enantiopure
      substrate. Bode's chiral acylated hydroxamic acids are very effective
      enantioselective acylating agents for a variety of amines. Pseudoenantiomers of
      these acyl-transfer reagents were prepared and demonstrated to react with
      enantiopure cyclic amines with modest to high selectivity. The products were
      analyzed by ESI-MS to determine selectivity, and the results were used to assign
      the configuration of the amine substrate. The method was applicable to a variety
      of cyclic amines as well as primary amines and acyclic secondary amines. The
      method is limited to amines that are unhindered enough to react with the
      reagents, and not all amine substitution patters lead to high selectivity.

PMID- 28763224
TI  - Development of a Video-Microscopic Tool To Evaluate the Precipitation Kinetics of
      Poorly Water Soluble Drugs: A Case Study with Tadalafil and HPMC.
AB  - Many drug candidates today have a low aqueous solubility and, hence, may show a
      low oral bioavailability, presenting a major formulation and drug delivery
      challenge. One way to increase the bioavailability of these drugs is to use a
      supersaturating drug delivery strategy. The aim of this study was to develop a
      video-microscopic method, to evaluate the effect of a precipitation inhibitor on
      supersaturated solutions of the poorly soluble drug tadalafil, using a novel
      video-microscopic small scale setup. Based on preliminary studies, a degree of
      supersaturation of 29 was chosen for the supersaturation studies with tadalafil
      in FaSSIF. Different amounts of hydroxypropyl methyl cellulose (HPMC) were
      predissolved in FaSSIF to give four different concentrations, and the
      supersaturated system was then created using a solvent shift method.
      Precipitation of tadalafil from the supersaturated solutions was monitored by
      video-microscopy as a function of time. Single-particle analysis was possible
      using commercially available software; however, to investigate the entire
      population of precipitating particles (i.e., their number and area covered in the
      field of view), an image analysis algorithm was developed (multiparticle
      analysis). The induction time for precipitation of tadalafil in FaSSIF was
      significantly prolonged by adding 0.01% (w/v) HPMC to FaSSIF, and the maximum
      inhibition was reached at 0.1% (w/v) HPMC, after which additional HPMC did not
      further increase the induction time. The single-particle and multiparticle
      analyses yielded the same ranking of the HPMC concentrations, regarding the
      inhibitory effect on precipitation. The developed small scale method to assess
      the effect of precipitation inhibitors can speed up the process of choosing the
      right precipitation inhibitor and the concentration to be used.

PMID- 28763225
TI  - Strong and Broadly Tunable Plasmon Resonances in Thick Films of Aligned Carbon
      Nanotubes.
AB  - Low-dimensional plasmonic materials can function as high quality terahertz and
      infrared antennas at deep subwavelength scales. Despite these antennas' strong
      coupling to electromagnetic fields, there is a pressing need to further
      strengthen their absorption. We address this problem by fabricating thick films
      of aligned, uniformly sized semiconducting carbon nanotubes and showing that
      their plasmon resonances are strong, narrow, and broadly tunable. With
      thicknesses ranging from 25 to 250 nm, our films exhibit peak attenuation
      reaching 70%, ensemble quality factors reaching 9, and electrostatically tunable
      peak frequencies by a factor of 2.3. Excellent nanotube alignment leads to the
      attenuation being 99% linearly polarized along the nanotube axis. Increasing the
      film thickness blueshifts the plasmon resonators down to peak wavelengths as low
      as 1.4 MUm, a new near-infrared regime in which they can both overlap the S11
      nanotube exciton energy and access the technologically important infrared telecom
      band.

PMID- 28763227
TI  - Strong Dependence of Quantum-Dot Delayed Luminescence on Excitation Pulse Width.
AB  - Delayed luminescence involving charge-carrier trapping and detrapping has
      recently been identified as a widespread and possibly universal phenomenon in
      colloidal quantum dots. Its near-power-law decay suggests a relationship with
      blinking. Here, using colloidal CuInS2 and CdSe quantum dots as model systems, we
      show that short (nanosecond) excitation pulses yield less delayed luminescence
      intensity and faster delayed luminescence decay than observed with long
      (millisecond) square-wave excitation pulses. Increasing the excitation power also
      affects the delayed luminescence intensity, but the delayed luminescence decay
      kinetics appear much less sensitive to excitation power than to excitation pulse
      width. An idealized four-state kinetic model reproduces the major experimental
      trends and highlights the very slow approach to steady state during
      photoexcitation, stemming from extremely slow detrapping of the metastable charge
      separated state responsible for delayed luminescence. The impacts of these
      findings on proposed relationships between delayed luminescence and blinking are
      discussed.

PMID- 28763228
TI  - Building Blocks for High Performance in Electrocatalytic CO2 Reduction:
      Materials, Optimization Strategies, and Device Engineering.
AB  - In recent years, screening of materials has yielded large gains in catalytic
      performance for the electroreduction of CO2. However, the diversity of approaches
      and a still immature mechanistic understanding make it challenging to assess the
      real potential of each concept. In addition, achieving high performance in CO2
      (photo)electrolyzers requires not only favorable electrokinetics but also precise
      device engineering. In this Perspective, we analyze a broad set of literature
      reports to construct a set of design-performance maps that suggest patterns
      between performance figures and different classes of materials and optimization
      strategies. These maps facilitate the screening of different approaches to
      electrocatalyst design and the identification of promising avenues for future
      developments. At the device level, analysis of the network of limiting phenomena
      in (photo)electrochemical cells leads us to propose a straightforward performance
      metric based on the concepts of maximum energy efficiency and maximum product
      formation rate, enabling the comparison of different technologies.

PMID- 28763226
TI  - Enhanced Brain Delivery of 2-(Phosphonomethyl)pentanedioic Acid Following
      Intranasal Administration of Its gamma-Substituted Ester Prodrugs.
AB  - 2-(Phosphonomethyl)pentanedioic acid (2-PMPA) is a potent and selective inhibitor
      of glutamate carboxypeptidase-II (GCPII) with efficacy in multiple neurological
      and psychiatric disease models, but its clinical utility is hampered by low brain
      penetration due to the inclusion of multiple acidic functionalities. We recently
      reported an improvement in the brain-to-plasma ratio of 2-PMPA after intranasal
      (IN) dosing in both rodents and primates. Herein, we describe the synthesis of
      several 2-PMPA prodrugs with further improved brain delivery of 2-PMPA after IN
      administration by masking of the gamma-carboxylate. When compared to IN 2-PMPA in
      rats at 1 h post dose, gamma-(4-acetoxybenzyl)-2-PMPA (compound 1) resulted in
      significantly higher 2-PMPA delivery to both plasma (4.1-fold) and brain (11
      fold). Subsequent time-dependent evaluation of 1 also showed high brain as well
      as plasma 2-PMPA exposures with brain-to-plasma ratios of 2.2, 0.48, and 0.26 for
      olfactory bulb, cortex, and cerebellum, respectively, as well as an improved
      sciatic nerve to plasma ratio of 0.84. In contrast, IV administration of compound
      1 resulted in similar plasma exposure of 2-PMPA versus the IN route (AUCIV: 76 +/
      9 h.nmol/mL versus AUCIN: 99 +/- 24 h.nmol/mL); but significantly lower nerve
      and brain tissue exposures with tissue-to-plasma ratios of 0.21, 0.03, 0.04, and
      0.04 in nerve, olfactory bulb, cortex, and cerebellum, respectively. In primates,
      IN administration of 1 more than doubled 2-PMPA concentrations in the
      cerebrospinal fluid relative to previously reported levels following IN 2-PMPA.
      The results of these experiments provide a promising strategy for testing GCPII
      inhibition in neurological and psychiatric disorders.

PMID- 28763229
TI  - Simulating Chemical Kinetics Without Differential Equations: A Quantitative
      Theory Based on Chemical Pathways.
AB  - A new approach is presented for simulating the time-evolution of chemically
      reactive systems. This method provides an alternative to conventional modeling of
      mass-action kinetics that involves solving differential equations for the species
      concentrations. The method presented here avoids the need to solve the rate
      equations by switching to a representation based on chemical pathways. In the Sum
      Over Histories Representation (or SOHR) method, any time-dependent kinetic
      observable, such as concentration, is written as a linear combination of
      probabilities for chemical pathways leading to a desired outcome. In this work,
      an iterative method is introduced that allows the time-dependent pathway
      probabilities to be generated from a knowledge of the elementary rate
      coefficients, thus avoiding the pitfalls involved in solving the differential
      equations of kinetics. The method is successfully applied to the model Lotka
      Volterra system and to a realistic H2 combustion model.

PMID- 28763231
TI  - In Situ STM and Vibrational Study of Nanometer-Scale Reorganization of a
      Phospholipid Monolayer Accompanied by Potential-Driven Headgroup Digestion.
AB  - In situ dynamic observation of model biological cell membranes, formed on a
      water/gold substrate interface, has been performed by the combination of
      electrochemical scanning tunneling microscopy and reflection infrared absorption
      vibrational spectroscopy. Monolayers of 1,2-dihexanoyl-sn-glycero-3
      phosphocholine (DHPC) were formed on alkanethiol-modified gold surfaces in a
      buffer solution, and the microscopic phase transitions driven by electrochemical
      potential control were observed more in detail than our previous study on the
      same system [Electrochem. Commun. 2007, 9, 645-650]. This time the transitions
      were associated with the chemistry of DHPC by the aid of vibrational spectroscopy
      and the utilization of deuterium-labeled DHPC molecules. A negative potential
      shift solidifies the fluidic lipid layers into static striped or grainy features
      without notable chemical reactions. The first positive potential shift over the
      virginal DHPC monolayer breaks DHPC into choline and the corresponding
      phosphatidic acid (DHPA). This is the first case of a phospholipid
      electrochemical reaction microscopically detected at the solid surface.

PMID- 28763230
TI  - Skin Delivery of Hydrophilic Biomacromolecules Using Marine Sponge Spicules.
AB  - We report the development of sponge Haliclona sp. spicules, referred to as SHS,
      and its topical application in skin delivery of hydrophilic biomacromolecules, a
      series of fluorescein isothiocyanate-dextrans (FDs). SHS are silicious oxeas
      which are sharp-edged and rod-shaped (~120 MUm in length and ~7 MUm in diameter).
      SHS can physically disrupt skin in a dose-dependent manner and retain within the
      skin over at least 72 h, which allows sustained skin penetration of hydrophilic
      biomacromolecules. The magnitude of enhancement of FD delivery into skin induced
      by SHS treatment was dependent on its molecular weight. Specifically, SHS topical
      application enhanced FD-10 (MW: 10 kDa) penetration into porcine skin in vitro by
      33.09 +/- 7.16-fold compared to control group (p < 0.01). SHS dramatically
      increased the accumulation of FD-10 into and across the dermis by 62.32 +/- 13.48
      fold compared to the control group (p < 0.01). In vivo experiments performed
      using BALB/c mice also confirmed the effectiveness of SHS topical application;
      the skin absorption of FD-10 with SHS topical application was 72.14 +/- 48.75
      fold (p < 0.05) and 15.39 +/- 9.91-fold (p < 0.05) higher than those from the PBS
      and Dermaroller microneedling, respectively. Further, skin irritation study and
      transepidermal water loss (TEWL) measurement using guinea pig skin in vivo
      indicated that skin disruption induced by SHS treatment is self-limited and can
      be recovered with time and efficiently. SHS can offer a safe, effective, and
      sustained skin delivery of hydrophilic biomacromolecules and presents a promising
      platform technology for a wide range of cosmetic and medical applications.

PMID- 28763232
TI  - Metal-Free Multiple Carbon-Carbon and Carbon-Hydrogen Bond Activations via Charge
      Switching Mechanism in Unstrained Diindolylmethanes.
AB  - A transformation of the unstrained phenol substituted 3,3'-diindolylmethanes
      (DIPMs) to 2,3'-diindolylketones (DIKs) by double C-C single bond cleavage with
      associated rearrangements, triggered by phenyliodine(III) diacetate (PIDA), is
      reported. Density functional theory studies reveal a mechanism involving multiple
      "charge-switching" steps by synergistic involvement of the two indole units with
      overall low activation energy. The indole 'charge-switching' mechanism in DIPMs
      was further extended toward synthesis of a natural product motif
      cyclohepta[b]indole from biaryl appended DIBM.

PMID- 28763233
TI  - Palladium-Catalyzed Multicomponent Reactions of o-Alkynylanilines, Aryl Iodides,
      and CO2 toward 3,3-Diaryl 2,4-Quinolinediones.
AB  - Palladium-catalyzed multicomponent reactions (MCRs) between o-alkynylanlines,
      aryl iodides, and atmospheric pressure of CO2 are developed, affording a series
      of 3,3-diaryl 2,4-quinolinediones bearing a newly constructed quaternary carbon
      center in moderate to excellent yields. The reaction proceeded with a sequential
      carboxylation, trans-oxopalladation of C=C bond by ArPdX species, and reductive
      elimination procedure leading to benzoxazine-2-ones bearing tetrasubstituted
      vinyl fragments. Then, rearrangement of benzoxazine-2-ones took place toward 3,3
      diaryl 2,4-quinolinediones. This procedure features simultaneous formation of
      four bonds in one pot.

PMID- 28763234
TI  - Palladium-Catalyzed Incorporation of Two C1 Building Blocks: The Reaction of
      Atmospheric CO2 and Isocyanides with 2-Iodoanilines Leading to the Synthesis of
      Quinazoline-2,4(1H,3H)-diones.
AB  - A Pd-catalyzed insertion and cycloaddition of CO2 and isocyanide into 2
      iodoanilines under atmospheric pressure has been developed and affords
      quinazoline-2,4(1H,3H)-diones through the formation of new C-C, C-O, and C-N
      bonds under mild conditions. This reaction provides a new and practical method
      not only for the construction of quinazoline-2,4(1H,3H)-diones but also for the
      efficient utilization of carbon dioxide.

PMID- 28763235
TI  - Total Synthesis and Structural Assignment of Curvicollide C.
AB  - The first total synthesis of (+)-curvicollide C has been accomplished. Cross
      metathesis and Julia-Kocienski olefination were instrumental in the synthesis of
      1,3-diene segments and allowed for a ternary-convergent synthetic design. A full
      structural assignment is proposed for (-)-curvicollide C, a uniquely structured
      polyketide of fungal origin.

PMID- 28763236
TI  - Hinge-Deficient IgG1 Fc Fusion: Application to Human Lactoferrin.
AB  - Fusion of therapeutic proteins with the antibody Fc domain is a strategy widely
      applied to increase protein half-life in plasma. In our previous study, we
      generated a recombinant human lactoferrin (hLF)-immunoglobulin G1 Fc fusion
      protein (hLF-hinge-CH2-CH3) with improved stability, biological activity, and
      pharmacokinetics ( Shiga , Y. et al. Eur J Pharm Sci. , 2015 , 67 , 136 - -143 ).
      However, the Fc domain in fusion proteins can potentially induce antibody
      dependent and complement-dependent cytotoxicity and serious side effects. To
      overcome these drawbacks, we engineered an hLF-Fc fusion protein (hLF-CH2-CH3)
      without the Fc hinge region which is essential for engaging Fc receptors on
      immune cells and inducing complement-mediated cell lysis. The hLF-CH2-CH3 protein
      was stably expressed in Chinese hamster ovary (CHO) DG44 cells and compared for
      in vitro activities, thermal stability, pharmacokinetics, and attenuation of Fc
      mediated immune effector functions with the conventional hinge-containing Fc
      fusion protein. Both hLF-hinge-CH2-CH3 and hLF-CH2-CH3 exhibited iron-binding
      activity, superior uptake by Caco-2 cells, similar thermal stability, and longer
      plasma half-life compared to recombinant hLF. However, in contrast to
      conventional hLF-hinge-CH2-CH3, hinge-deficient hLF-CH2-CH3 did not elicit Fc
      mediated effector response potentially damaging for the target cells. Our
      findings demonstrate that conjugation of hinge-deficient Fc to therapeutic
      proteins is a promising strategy for improving their pharmacokinetic properties
      without enhancing effector functions. Cell-expressed hinge-deficient hLF-CH2-CH3
      is a potential drug candidate with improved plasma half-life for parenteral
      administration.

PMID- 28763237
TI  - Changing shape: evolving an outsourced bioanalytical strategy to support the
      changing needs of drug development.

PMID- 28763238
TI  - Method transfer: a CRO perspective.

PMID- 28763239
TI  - Detecting New Mycobacterium tuberculosis Infection. Time for a More Nuanced
      Interpretation of QuantiFERON Conversions.

PMID- 28763240
TI  - Dead biomass of Amazon yeast: A new insight into bioremediation and recovery of
      silver by intracellular synthesis of nanoparticles.
AB  - This investigation was undertaken to describe a natural process for the removal
      of silver and the simultaneous recovery of Ag/Ag2O nanoparticles by dead biomass
      of the yeast Rhodotorula mucilaginosa. The removal of silver ions from aqueous
      solution and the synthesis of Ag/Ag2O nanoparticles were analyzed based on
      physicochemical factors and equilibrium concentration, combined with transmission
      electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive
      X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and infrared
      spectroscopy (FTIR). A successful process for the synthesis of Ag/Ag2O
      nanoparticles was obtained, following the Langmuir isotherm model, showing a high
      biosorption capacity of silver (49.0 mg g-1). The nanoparticles were spherical,
      had an average size of 11.0 nm, were synthesized intracellularly and capped by
      yeast proteins. This sustainable protocol is an attractive platform for the
      industrial-scale production of silver nanoparticles and of a silver
      nanobiosorbent.

PMID- 28763242
TI  - Correction to: Sisto et al., Abnormal distribution of AQP4 in minor salivary
      glands of primary Sjogren's syndrome patients.

PMID- 28763241
TI  - The changing world of bioanalysis: summary of panel discussions.

PMID- 28763243
TI  - Randomized, double-blind trial evaluating the efficacy and safety of fluticasone
      propionate and fluticasone propionate/salmeterol delivered via multidose dry
      powder inhalers in patients with persistent asthma aged 12 years and older.
AB  - OBJECTIVE: To assess the efficacy and safety of fluticasone propionate (Fp) and
      Fp/salmeterol (FS) administered via a novel multidose dry powder inhaler (MDPI)
      that is easy to use correctly in asthma patients. METHODS: This phase-3,
      multicenter, double-blind, parallel-group study evaluated asthmatic patients
      (>=12 years of age) previously treated with either low- or mid-dose inhaled
      corticosteroids (ICSs) or ICS/long-acting beta agonists. After a 14- to 21-day
      run-in, patients were randomized to Fp MDPI 50 mcg, Fp MDPI 100 mcg, FS MDPI
      50/12.5 mcg, FS MDPI 100/12.5 mcg, or placebo twice daily for 12 weeks. Change
      from baseline in forced expiratory volume in 1 second (FEV1; primary endpoint)
      was evaluated at week 12, and serial spirometry was collected at day 1 and week
      12 (subset of patients). Safety was assessed by adverse events (AEs). RESULTS:
      The full analysis and serial spirometry subset included 640 and 312 patients,
      respectively. At week 12, FS MDPI significantly improved FEV1 from baseline at
      each dose vs corresponding Fp MDPI doses (p < 0.05). Change from baseline in FEV1
      for active treatment groups was significantly greater vs placebo (p < 0.05).
      After 12 weeks, serial spirometry was significantly greater at all time points in
      the FS MDPI groups vs corresponding Fp MDPI groups (p < 0.05). Improvements in
      serial spirometry on day 1 were maintained through week 12. AEs were similar
      across groups. CONCLUSIONS: Pulmonary function was significantly improved with Fp
      MDPI and FS MDPI vs placebo and FS MDPI vs Fp MDPI. Active treatments had a
      safety profile comparable to placebo.

PMID- 28763244
TI  - More Breathing, Less Fitness: Lessons from Exercise Physiology in Chronic
      Obstructive Pulmonary Disease-Heart Failure Overlap.

PMID- 28763245
TI  - Bioanalytical outsourcing strategy in China.

PMID- 28763246
TI  - Autofluorescence and Nonspecific Immunofluorescent Labeling in Frozen Bovine
      Intestinal Tissue Sections: Solutions for Multicolor Immunofluorescence
      Experiments.
AB  - Autofluorescent compounds present in intestinal tissue often hinder the ability
      to utilize multiple, spectrally different, fluorophores. In addition, fixatives
      and blocking solutions may contribute to background autofluorescence or
      nonspecific immunofluorescent labeling. During immunofluorescence protocol
      development, autofluorescent pigments were observed in frozen bovine mid-ileal
      intestinal tissue sections. Coagulant fixatives, normal serum blocking,
      histochemical stains Sudan Black B (SBB) and 3,3'-diaminobenzidine (DAB), and
      spectral separation using imaging software were compared for their ability to
      reduce autofluorescence, as well as their effect on immunofluorescent labeling.
      Fluorescent pigments of frozen bovine mid-ileal intestinal tissue sections, most
      likely caused by eosinophils and lipofuscin, were masked successfully with a
      combination of DAB and SBB. Little to no statistical differences were observed
      for all other methods investigated; however, tissue fixed with 1:1 acetone
      methanol and 10% horse serum diluted in 0.05 M Tris buffer demonstrated lower
      mean fluorescence intensities. Spectral separation of specific immunofluorescent
      labeling from background autofluorescence is a simple method for removing
      unwanted fluorescence; however, successful separation is dependent on tissue and
      labeling quality.

PMID- 28763247
TI  - Capillary blood for point-of-care testing.
AB  - Clinically, blood sample analysis has been widely used for health monitoring. In
      hospitals, arterial and venous blood are utilized to detect various disease
      biomarkers. However, collection methods are invasive, painful, may result in
      injury and contamination, and skilled workers are required, making these methods
      unsuitable for use in a resource-limited setting. In contrast, capillary blood is
      easily collected by a minimally invasive procedure and has excellent potential
      for use in point-of-care (POC) health monitoring. In this review, we first
      discuss the differences among arterial blood, venous blood, and capillary blood
      in terms of the puncture sites, components, sample volume, collection methods,
      and application areas. Additionally, we review the most recent advances in
      capillary blood-based commercial products and microfluidic instruments for
      various applications. We also compare the accuracy of microfluidic-based testing
      with that of laboratory-based testing for capillary blood-based disease diagnosis
      at the POC. Finally, we discuss the challenges and future perspectives for
      developing capillary blood-based POC instruments.

PMID- 28763248
TI  - Evaluating Commercially Available Antibodies for Rat alpha7 Nicotinic
      Acetylcholine Receptors.
AB  - Alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) are important drug
      targets in neurological disorders and inflammation, making their detection and
      localization by validated antibodies highly desirable. However, tests in knockout
      animals raised questions about specificity of antibodies to mouse alpha7 nAChRs.
      To date, methods for validating antibodies for rat or human alpha7 nAChR have not
      been reported. We developed a gel-shift assay for western blots using GH4C1 cells
      expressing either native rat receptors or alpha7 nAChR-green fluorescent protein
      (GFP) chimeras to evaluate seven commercially available alpha7 nAChR antibodies.
      Blots with anti-GFP antibody detected GFP or alpha7 nAChR-GFP expressed in GH4C1
      cells, and 125I-alpha-bungarotoxin binding and RNA analysis demonstrated alpha7
      nAChR expression. Validated samples were used to evaluate alpha7 nAChR antibodies
      by western blot and immunofluorescence studies. These methods confirmed that two
      of seven alpha7 nAChR antibodies identify gel-shifts for alpha7 nAChR/nAChR-GFP
      but only one antibody demonstrated low background and significant
      immunofluorescence differences between wild-type and alpha7 nAChR expressing
      GH4C1 cells. However, that polyclonal antibody displayed lot-to-lot variability.
      Our findings suggest that careful validation methods are required for all alpha7
      nAChR receptor species and antibody lots and that the gel-shift assay may allow
      for relatively rapid antibody screening.

PMID- 28763249
TI  - Interactions between clients and outsourced CROs: mind the gap.

PMID- 28763250
TI  - Bioanalytical outsourcing models in pharmaceutical companies.

PMID- 28763252
TI  - The Book Corner.

PMID- 28763251
TI  - Meetings & Symposia.

PMID- 28763254
TI  - Decolorization of textile dyes in an air-lift bioreactor inoculated with
      Bjerkandera adusta OBR105.
AB  - A new decolorizing white-rot fungus, OBR105, was isolated from Mount Odae in
      South Korea and identified by the morphological characterization of its fruit
      body and spores and partial 18s rDNA sequences. The ligninolytic enzyme activity
      of OBR105 was studied to characterize their decolorizing mechanism using a
      spectrophotometric enzyme assay. For the evaluation of the decolorization
      capacity of OBR105, the isolate was incubated in an erlenmeyer flask and in an
      airlifte bioreator with potato dextrose broth (PDB) medium supplemented with each
      dye. In addition, the decolorization efficiency of real textile wastewater was
      evaluated in an airlift bioreactor inoculated with the isolate. The isolate was
      identified as Bjerkandera adusta and had ligninolytic enzymes such as laccase,
      lignin peroxidase (LiP), and Mn-dependent peroxidase (MnP). Its LiP activity was
      higher than its MnP and laccase activities. B. adusta OBR105 successfully
      decolorized reactive dyes (red 120, blue 4, orange 16, and black 5) and acid dyes
      (red 114, blue 62, orange 7, and black 172). B. adusta OBR105 decolorized 91-99%
      of 200 mg L-1 of each dye (except acid orange 7) within 3 days in a PDB medium at
      28 degrees C, pH 5, and 150 rpm. This fungus decolorized only 45% of 200 mg L-1
      acid orange 7 (single azo-type dye) within 3 days, and the decolorization
      efficiency did not increase by prolonging the cultivation time. In the air-lift
      bioreactor, B. adusta OBR105 displayed a high decolorization capacity, greater
      than 90%, for 3 acid dyes (red 114, blue 62, and black 172) and 1 reactive dye
      (blue 4) within 10-15 h of treatment. B. adusta OBR105 could decolorize real
      textile wastewater in the air-lift bioreactor. This result suggests that an air
      lift reactor employing B. adusta OBR105 is a promising bioreactor for the
      treatment of dye wastewater.

PMID- 28763253
TI  - Alda-1 Protects Against Acrolein-Induced Acute Lung Injury and Endothelial
      Barrier Dysfunction.
AB  - Inhalation of acrolein, a highly reactive aldehyde, causes lung edema. The
      underlying mechanism is poorly understood and there is no effective treatment. In
      this study, we demonstrated that acrolein not only dose-dependently induced lung
      edema but also promoted LPS-induced acute lung injury. Importantly, acrolein
      induced lung injury was prevented and rescued by Alda-1, an activator of
      mitochondrial aldehyde dehydrogenase 2. Acrolein also dose-dependently increased
      monolayer permeability, disrupted adherens junctions and focal adhesion
      complexes, and caused intercellular gap formation in primary cultured lung
      microvascular endothelial cells (LMVECs). These effects were attenuated by Alda-1
      and the antioxidant N-acetylcysteine, but not by the NADPH inhibitor apocynin.
      Furthermore, acrolein inhibited AMP-activated protein kinase (AMPK) and increased
      mitochondrial reactive oxygen species levels in LMVECs-effects that were
      associated with impaired mitochondrial respiration. AMPK total protein levels
      were also reduced in lung tissue of mice and LMVECs exposed to acrolein.
      Activation of AMPK with 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside
      blunted an acrolein-induced increase in endothelial monolayer permeability, but
      not mitochondrial oxidative stress or inhibition of mitochondrial respiration.
      Our results suggest that acrolein-induced mitochondrial dysfunction may not
      contribute to endothelial barrier dysfunction. We speculate that detoxification
      of acrolein by Alda-1 and activation of AMPK may be novel approaches to prevent
      and treat acrolein-associated acute lung injury, which may occur after smoke
      inhalation.

PMID- 28763255
TI  - Transurethral resection of the prostate achieves favorable outcomes in stroke
      patients with symptomatic benign prostate hyperplasia.
AB  - OBJECTIVES: To evaluate the surgical outcomes of stroke patients with symptomatic
      benign prostatic hyperplasia (BPH) who underwent transurethral resection of the
      prostate (TURP) and compare the clinical outcomes between patients with stroke
      and those without stroke receiving this procedure. METHODS: This retrospective
      cohort study analyzed claims data collected during the period of 1997-2012 from
      Taiwan National Health Insurance Research Database. We enrolled 6625 patients who
      had persistent lower urinary tract symptoms and underwent TURP for BPH. They were
      categorized into a stroke (n = 577) and nonstroke (n = 6048) group. Patient
      characteristics, postoperative clinical outcomes, medication records, and medical
      expenses were compared. RESULTS: Compared with the stroke group patients, those
      in the nonstroke group were younger, had fewer comorbidities, and more favorable
      postoperative clinical outcomes. Nevertheless, TURP achieved favorable outcomes
      in stroke patients with symptomatic BPH. In the stroke group, the rate of urinary
      tract infection (UTI) decreased from 34.7% during 1 year preoperatively to 29.8%
      during 1 year postoperatively (p = .05). The rate of urinary retention (UR) also
      decreased from 55.5% during 1 year preoperatively to 22.5% during 1 year
      postoperatively (p = .05). TURP reduced the overall medical expenses of patients
      with stroke. Annual patient medical expense during 1 year preoperatively, 1 year
      postoperatively, 2 years postoperatively, and 3 years postoperatively was
      NT$659,000, NT$646,000, NT$560,000, and NT$599,000, respectively. CONCLUSIONS: In
      patients with stroke, TURP reduces the risks of UTI and UR and annual total
      medical expense.

PMID- 28763257
TI  - Bioanalytical outsourcing: transitioning from Pharma to CRO.

PMID- 28763256
TI  - Cytokine profile of breast cell lines after different radiation doses.
AB  - PURPOSE: Ionizing radiation (IR) treatment activates inflammatory processes
      causing the release of a great amount of molecules able to affect the cell
      survival. The aim of this study was to analyze the cytokine signature of
      conditioned medium produced by non-tumorigenic mammary epithelial cell line
      MCF10A, as well as MCF7 and MDA-MB-231 breast cancer cell lines, after single
      high doses of IR in order to understand their role in high radiation response.
      MATERIALS AND METHODS: We performed a cytokine profile of irradiated conditioned
      media of MCF10A, MCF7 and MDA-MB-231 cell lines treated with 9 or 23 Gy, by
      Luminex and ELISA analyses. RESULTS: Overall, our results show that both 9 Gy and
      23 Gy of IR induce the release within the first 72 h of cytokines and growth
      factors potentially able to influence the tumor outcome, with a dose-independent
      and cell-line dependent signature. Moreover, our results show that the cell
      senescence phenomenon does not correlate with the amount of 'senescence
      associated secretory phenotype' (SASP) molecules released in media. Thus,
      additional mechanisms are probably involved in this process. CONCLUSIONS: These
      data open the possibility to evaluate cytokine profile as useful marker in
      modulating the personalized radiotherapy in breast cancer care.

PMID- 28763258
TI  - Cyclin D2 is sufficient to drive beta cell self-renewal and regeneration.
AB  - Diabetes results from an inadequate mass of functional beta cells, due to either
      beta cell loss caused by autoimmune destruction (type I diabetes) or beta cell
      failure in response to insulin resistance (type II diabetes). Elucidating the
      mechanisms that regulate beta cell mass may be key to developing new techniques
      that foster beta cell regeneration as a cellular therapy to treat diabetes. While
      previous studies concluded that cyclin D2 is required for postnatal beta cell
      self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive beta
      cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically
      in beta cells, we show that cyclin D2 overexpression increases beta cell self
      renewal post-weaning and results in increased beta cell mass. beta cells that
      overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are
      functionally mature. beta cells that overexpress cyclin D2 demonstrate an
      enhanced regenerative capacity after injury induced by streptozotocin toxicity.
      To understand if cyclin D2 overexpression is sufficient to drive beta cell self
      renewal, we generated a novel mouse model where cyclin D2 is only expressed in
      beta cells of cyclin D2-/- mice. Transgenic overexpression of cyclin D2 in cyclin
      D2-/- beta cells was sufficient to restore beta cell mass, maintain
      normoglycaemia, and improve regenerative capacity when compared with cyclin D2-/-
      littermates. Taken together, our results indicate that cyclin D2 is sufficient to
      regulate beta cell self-renewal and that manipulation of its expression could be
      used to enhance beta cell regeneration.

PMID- 28763259
TI  - Strategies for Introducing Outpatient Specialty Palliative Care in Gynecologic
      Oncology.
AB  - PURPOSE: Concern that patients will react negatively to the idea of palliative
      care is cited as a barrier to timely referral. Strategies to successfully
      introduce specialty palliative care to patients have not been well described. We
      sought to understand how gynecologic oncologists introduce outpatient specialty
      palliative care. METHODS: We conducted a national qualitative interview study at
      six geographically diverse academic cancer centers with well-established
      palliative care clinics between September 2015 and March 2016. Thirty-four
      gynecologic oncologists participated in semistructured telephone interviews
      focusing on attitudes, experiences, and practices related to outpatient
      palliative care. A multidisciplinary team analyzed interview transcripts using
      constant comparative methods to inductively develop and refine a coding
      framework. This analysis focuses on practices for introducing palliative care.
      RESULTS: Mean participant age was 47 years (standard deviation, 10 years). Mean
      interview length was 25 minutes (standard deviation, 7 minutes). Gynecologic
      oncologists described the following three main strategies for introducing
      outpatient specialty palliative care: focus initial palliative care referral on
      symptom management to dissociate palliative care from end-of-life care and
      facilitate early relationship building with palliative care clinicians; use a
      strong physician-patient relationship and patient trust to increase acceptance of
      referral; and explain and normalize palliative care referral to address negative
      associations and decrease patient fear of abandonment. These strategies aim to
      decrease negative patient associations and encourage acceptance of early referral
      to palliative care specialists. CONCLUSION: Gynecologic oncologists have
      developed strategies for introducing palliative care services to alleviate
      patient concerns. These strategies provide groundwork for developing system-wide
      best practice approaches to the presentation of palliative care referral.

PMID- 28763261
TI  - Yoga Therapy in Japan.
AB  - This perspective piece gives an overview of the current situation of yoga therapy
      in Japan today. Traditional yoga in Japan suffered a serious setback in 1995 with
      a nerve gas terrorist attack on the Tokyo subway, which was carried out by a cult
      that recruited members through yoga classes. But with the increase in popularity
      with modern forms of yoga such as Iyengar yoga, Ashtanga yoga and hot yoga in the
      West, the general public in Japan today is forgetting its aversion to yoga and
      considers it to be something that can contribute to good health. In 2012, the
      Japan Yoga Therapy Society (JYTS) conducted a study on adverse events in yoga
      classes throughout Japan with the University of Kyushu School of Medicine, with
      support from the Ministry of Health, Labour and Welfare. This study indicated
      that more than half of people attending yoga classes have some form of chronic
      illness, with 42.3% receiving outpatient care. This survey was the beginning of
      growing interest from both the government and universities in yoga therapy. JYTS
      is beginning to make inroads into bringing yoga therapy into cancer and
      palliative care, senior citizen homes, alcohol and drug addiction rehabilitation,
      cardiovascular rehabilitation, and research on trauma and schizophrenia. While
      there are still limited opportunities for yoga therapists to work in mainstream
      healthcare services, there is growing interest among medical professionals in
      both physical and mental health. JYTS is beginning to make inroads into bringing
      yoga therapy into cancer and palliative care, senior citizen homes, alcohol and
      drug addiction rehabilitation, cardiovascular rehabilitation, and research on
      trauma and schizophrenia. While there are still limited opportunities for yoga
      therapists to work in mainstream healthcare services, there is growing interest
      among medical professionals in both physical and mental health. This perspective
      piece introduces some of the developments in yoga therapy research and practice
      in Japan.

PMID- 28763260
TI  - Patterns of Resuscitation Care and Survival After In-Hospital Cardiac Arrest in
      Patients With Advanced Cancer.
AB  - PURPOSE: Little is known regarding patterns of resuscitation care in patients
      with advanced cancer who suffer in-hospital cardiac arrest (IHCA). METHODS: In
      the Get With The Guidelines - Resuscitation registry, 47,157 adults with IHCA
      with and without advanced cancer (defined as the presence of metastatic or
      hematologic malignancy) were identified at 369 hospitals from April 2006 through
      June 2010. We compared rates of return of spontaneous circulation (ROSC) and
      survival to discharge between groups using multivariable models. We also compared
      duration of resuscitation effort and resuscitation quality measures. RESULTS:
      Overall, 6,585 patients with IHCA (14.0%) had advanced cancer. Patients with
      advanced cancer had lower multivariable-adjusted rates of ROSC (52.3% [95% CI,
      49.5% to 55.3%] v 56.6% [95% CI, 53.8% to 59.5%]; P < .001) and survival to
      discharge (7.4% [95% CI, 6.6% to 8.4%] v 13.4% [95% CI, 12.1% to 14.8%]; P <
      .001). Among nonsurvivors who died during resuscitation, patients with advanced
      cancer had better performance on most resuscitation quality measures. Among
      patients with ROSC, patients with advanced cancer were made Do Not Attempt
      Resuscitation (DNAR) more frequently within 48 hours (adjusted relative risk,
      1.30 [95% CI, 1.24 to 1.37]; P < .001). Adjustment for DNAR status explained some
      of the immediate effect of advanced cancer on survival; however, survival
      remained significantly lower in patients with cancer. CONCLUSION: Patients with
      advanced cancer can expect lower survival rates after IHCA compared with those
      without advanced cancer, and they are more frequently made DNAR within 48 hours
      of ROSC. These findings have important implications for discussions of
      resuscitation care wishes with patients and can better inform end-of-life
      discussions.

PMID- 28763262
TI  - Guidelines for teaching yoga to women with breast cancer-related lymphoedema: an
      evidence-based approach.
AB  - Breast cancer-related lymphoedema (BCRL) is a chronic condition that requires
      lifelong management to prevent the condition worsening and to reduce the threat
      of infection. Women are affected in all domains of their life. As a holistic
      practice, yoga may be of benefit by reducing both the physical and psychosocial
      effects of lymphoedema. Women with BCRL are attending yoga classes in increasing
      numbers, so it is essential that yoga be based on principles that ensure
      lymphoedema is controlled and not exacerbated. Two Randomised Controlled Trials
      with a yoga intervention have had positive results after an 8-week intervention
      (n=28) and 6-months after a 4-week intervention (n=18). The first study had
      several significant results and women reported increased biopsychosocial
      improvements. Both studies showed trends to improved lymphoedema status. The yoga
      interventions compromised breathing, physical postures, meditation and relaxation
      practices based on Satyananda Yoga(r), with modifications to promote lymphatic
      drainage and following principles of best current care for those with BCRL.
      Individual needs were considered. The yoga protocol that was used in the 8-week
      trial is presented. Our aim is to provide principles for yoga teachers/therapists
      working with this clientele that can be adapted to other yoga styles. Further,
      these principles may provide a basis for the development of yoga programs for
      people with secondary lymphoedema in other areas of their body as the population
      requiring cancer treatment continues to increase. Whilst the style of yoga
      presented here has had positive outcomes, further application and research is
      needed to fully demonstrate its effectiveness.

PMID- 28763263
TI  - Interpretive phenomenological analysis of a lawsuit contending that school-based
      yoga is religion: A study of school personnel.
AB  - This study focused on the perspectives of school personnel affiliated with the
      Encinitas Union School District in California following a lawsuit arguing that
      their yoga-based program included religion and therefore was unsuitable for
      implementation in public schools and was unconstitutional. Participants (N = 32)
      were interviewed using a semistructured interview, and data were analyzed
      according to Interpretative Phenomenological Analysis. Five super-ordinate themes
      (including sub-themes) were identified in an iterative process, including:
      participants' perspectives on the roots of yoga and the type of yoga taught in
      their district; the process of introducing a yoga-in-the-schools program in light
      of this contention (including challenges and obstacles, and how these were met);
      perspectives on the lawsuit and how the process unfolded; effects of the lawsuit
      on school climate and beyond; and perspectives on yoga as, and as not, religious.
      The study attempts to shed light on the impact of an ongoing lawsuit on a school
      district at the time of implementation of a program for students' well being.

PMID- 28763264
TI  - Measures of Frailty in Chronic Lung Diseases.

PMID- 28763265
TI  - Acute Hypoxemic Respiratory Failure Presenting with Centrilobular Nodules on
      Computed Tomographic Pulmonary Angiography.

PMID- 28763266
TI  - Insights into the Treatment of Severe Pulmonary Alveolar Proteinosis.

PMID- 28763267
TI  - An Official American Thoracic Society Workshop Report: Translational Research in
      Rare Respiratory Diseases.
AB  - Rare respiratory diseases (RRDs) are a heterogeneous group of disorders that
      collectively represent a significant health care burden. In recent years, strong
      advocacy and policy initiatives have led to advances in the implementation of
      research and clinical care for rare diseases. The development of specialized
      centers and research networks has facilitated support for affected individuals as
      well as emerging programs in basic, translational, and clinical research. In
      selected RRDs, subsequent gains in knowledge have informed the development of
      targeted therapies and effective diagnostic tests, but many gaps persist. There
      was therefore a desire to identify the elements contributing to an effective
      translational research program in RRDs. To this end, a workshop was convened in
      October 2015 with a focus on the implementation of effective transnational
      research networks and collaborations aimed at developing novel diagnostic and
      therapeutic tools. Key elements included an emphasis on molecular pathogenesis,
      the continuing engagement of patient advocacy groups and policy makers, the
      effective use of preclinical models in the translational research pipeline, and
      the detailed phenotyping of patient cohorts. During the course of the workshop,
      current logistical and knowledge gaps were identified, and new solutions or
      opportunities were highlighted.

PMID- 28763268
TI  - Chronic Hypoxemia in a 2-Year-Old Boy.

PMID- 28763269
TI  - Summary for Clinicians: Mechanical Ventilation in Adult Patients with Acute
      Respiratory Distress Syndrome Clinical Practice Guideline.

PMID- 28763270
TI  - What Is Your Diagnosis? Tooth root abscess.

PMID- 28763272
TI  - What Is Your Neurologic Diagnosis?

PMID- 28763274
TI  - Letters to the Editor.

PMID- 28763273
TI  - Diagnosis and treatment of esophageal foreign body or stricture in three ferrets
      (Mustela putorius furo).
AB  - CASE DESCRIPTION 3 ferrets (Mustela putorius furo), aged 1 to 2 years, were
      referred for evaluation of a 4-day to 2-week history of gastrointestinal signs,
      including anorexia, regurgitation, and vomiting. CLINICAL FINDINGS All 3 ferrets
      had clinical signs suggestive of dysphagia or esophagitis on initial examination.
      Esophagoscopy, barium-contrast esophagography, or both revealed foreign bodies
      with mucosal inflammation in 1 patient and an esophageal foreign body with
      stricture in 2 patients. One of the latter ferrets had a recent history of
      gastrotomy to remove a foreign body. TREATMENT AND OUTCOME 1 ferret was treated
      with endoscopic retrieval of the foreign bodies. Esophageal stricture was treated
      in 2 ferrets by means of endoscopic balloon dilation accompanied by placement of
      an esophageal stent in 1 ferret. After resolution of clinical signs and
      completion of all prescribed treatments, 2 of 3 ferrets successfully transitioned
      to a regular hard kibble diet; 1 ferret remained on a soft diet for 2 years. All
      owners were satisfied with the outcome of treatment. CLINICAL RELEVANCE Ferrets
      are prone to foreign body ingestion. Results of this small series of cases
      suggested that minimally invasive techniques may be useful for the management of
      esophageal disease in this species.

PMID- 28763275
TI  - Cytologic comparison of the percentage of mast cells in lymph node aspirate
      samples from clinically normal dogs versus dogs with allergic dermatologic
      disease and dogs with cutaneous mast cell tumors.
AB  - OBJECTIVE To compare percentages of mast cells in lymph node (LN) aspirate
      samples from clinically normal dogs, dogs with allergic dermatologic disease
      (ADD), and dogs with cutaneous mast cell tumors (MCTs). DESIGN Prospective cross
      sectional study. ANIMALS 20 healthy dogs (group 1), 20 dogs with ADD (group 2),
      and 20 dogs with an MCT on the head or limbs (group 3). PROCEDURES LN aspirate
      samples were obtained from easily accessible LNs in group 1, affected skin
      regions in group 2, and the likely draining LN or LNs of the MCT in group 3; the
      percentage of mast cells was manually determined for each LN. For group 3, LNs
      were cytologically categorized with a modified version of a published metastasis
      categorization scheme. RESULTS Median (range) percentage of mast cells in
      aspirate samples was 0% (0% to 0.1%) for group 1, 0.05% (0% to 0.55%) for group
      2, and 0.4% (0% to 77.4%) for group 3. In group 3, 16 LNs (13 dogs) were palpably
      normal in size; 6 of these had evidence of possible or certain metastasis. Seven
      LNs (7 dogs) in group 3 were palpably enlarged, and 5 of these had evidence of
      certain metastasis. CONCLUSIONS AND CLINICAL RELEVANCE This study provided
      evidence to support the use of a uniform cytologic grading system to further
      define nodal metastasis in dogs with MCTs as well as estimates of the percentage
      of mast cells in LN aspirate samples for healthy dogs and dogs with ADD. Palpably
      normal LNs in dogs with cutaneous MCT may contain metastasis.

PMID- 28763276
TI  - Outcome of laparoscopic ovariectomy and laparoscopic-assisted ovariohysterectomy
      in dogs: 278 cases (2003-2013).
AB  - OBJECTIVE To compare outcomes for laparoscopic ovariectomy (LapOVE) and
      laparoscopic-assisted ovariohysterectomy (LapOVH) in dogs. DESIGN Retrospective
      case series. ANIMALS 278 female dogs. PROCEDURES Medical records of female dogs
      that underwent laparoscopic sterilization between 2003 and 2013 were reviewed.
      History, signalment, results of physical examination, results of preoperative
      diagnostic testing, details of the surgical procedure, durations of anesthesia
      and surgery, intraoperative and immediate postoperative (ie, during
      hospitalization) complications, and short- (<= 14 days after surgery) and long
      term (> 14 days after surgery) outcomes were recorded. Data for patients
      undergoing LapOVE versus LapOVH were compared. RESULTS Intraoperative and
      immediate postoperative complications were infrequent, and incidence did not
      differ between groups. Duration of surgery for LapOVE was significantly less than
      that for LapOVH; however, potential confounders were not assessed. Surgical site
      infection was identified in 3 of 224 (1.3%) dogs. At the time of long-term follow
      up, postoperative urinary incontinence was reported in 7 of 125 (5.6%) dogs that
      underwent LapOVE and 12 of 82 (14.6%) dogs that underwent LapOVH. None of the
      dogs had reportedly developed estrus or pyometra by the time of final follow-up.
      Overall, 205 of 207 (99%) owners were satisfied with the surgery, and 196 of 207
      (95%) would consider laparoscopic sterilization for their dogs in the future.
      CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that short- and long-term
      outcomes were similar for female dogs undergoing sterilization by means of LapOVE
      or LapOVH; however, surgery time may have been shorter for dogs that underwent
      LapOVE. Most owners were satisfied with the outcome of laparoscopic
      sterilization.

PMID- 28763278
TI  - In This Issue * August 15, 2017.

PMID- 28763277
TI  - Anesthesia Case of the Month.

PMID- 28763279
TI  - Effect of a synthetic feline facial pheromone product on stress scores and
      incidence of upper respiratory tract infection in shelter cats.
AB  - OBJECTIVE To determine whether a synthetic feline facial pheromone product would
      decrease stress scores and upper respiratory tract infection (URI) incidence in
      shelter-housed cats. DESIGN Randomized controlled clinical trial. ANIMALS 336
      stray, feral, owner-relinquished, or legally impounded cats at 2 animal shelters
      in northern California. PROCEDURES 5 cat holding rooms (3 at shelter A and 2 at
      shelter B) were used. A diffuser containing either synthetic pheromone or placebo
      was randomly assigned to each room, and cats were exposed for a 21-day period.
      Data collected on each cat included signalment, daily stress scores, and daily
      URI incidence. After 21 days, diffusers were removed for a 7-day washout period.
      The type of diffuser in each room was switched, and data were collected for
      another 21 days. Findings were statistically compared between exposure types and
      other groupings. RESULTS Cox proportional hazard analysis revealed no significant
      difference between exposure (pheromone or placebo) and URI incidence. Mixed
      effects ordinal logistic regression revealed no significant relationship between
      exposure and daily stress scores. Three covariates had significant ORs: number of
      days in holding (OR, 0.80; 95% confidence interval [CI], 0.76 to 0.84), owner
      relinquished versus stray (OR, 3.25; 95% CI, 1.18 to 8.94), and feral versus
      adult cat room at shelter A (OR, 11.10; 95% CI, 4.47 to 27.60). CONCLUSIONS AND
      CLINICAL RELEVANCE No evidence was found that the evaluated synthetic feline
      facial pheromone product had any effect on stress scores or URI incidence in
      shelter-housed cats. Therefore, other established methods for stress and URI
      reduction should be used in shelter settings.

PMID- 28763280
TI  - Multicenter evaluation of signalment and comorbid conditions associated with
      aortic thrombotic disease in dogs.
AB  - OBJECTIVE To assess signalment and concurrent disease processes in dogs with
      aortic thrombotic disease (ATD). DESIGN Retrospective case-control study. ANIMALS
      Dogs examined at North American veterinary teaching hospitals from 1985 through
      2011 with medical records submitted to the Veterinary Medical Database.
      PROCEDURES Medical records were reviewed to identify dogs with a diagnosis of ATD
      (case dogs). Five control dogs without a diagnosis of ATD were then identified
      for every case dog. Data were collected regarding dog age, sex, breed, body
      weight, and concurrent disease processes. RESULTS ATD was diagnosed in 291 of the
      984,973 (0.03%) dogs included in the database. The odds of a dog having ATD did
      not differ significantly by sex, age, or body weight. Compared with mixed-breed
      dogs, Shetland Sheepdogs had a significantly higher odds of ATD (OR, 2.59).
      Protein-losing nephropathy (64/291 [22%]) was the most commonly recorded
      concurrent disease in dogs with ATD. CONCLUSIONS AND CLINICAL RELEVANCE Dogs with
      ATD did not differ significantly from dogs without ATD in most signalment
      variables. Contrary to previous reports, cardiac disease was not a common
      concurrent diagnosis in dogs with ATD.

PMID- 28763281
TI  - Pathology in Practice. Systemic bibersteiniosis .

PMID- 28763282
TI  - Comparison between double-pigtail ureteral stents and ureteral bypass devices for
      treatment of ureterolithiasis in cats.
AB  - OBJECTIVE To compare the complication rates and outcomes in cats with ureteral
      obstruction treated by placement of double-pigtail ureteral stents or ureteral
      bypass (UB) devices. DESIGN Retrospective cohort study. ANIMALS Cats with
      unilateral or bilateral ureterolithiasis that received double-pigtail ureteral
      stents (30 stents in 27 cats; stent group) or UB devices (30 devices in 23 cats;
      UB group). PROCEDURES Medical records were reviewed to collect data on
      signalment, clinical signs, serum biochemical data, surgical procedure, duration
      of hospitalization, complications, and follow-up (>= 6 months after placement)
      information. Outcomes were compared between device types. RESULTS Median
      durations of surgery and hospitalization were significantly longer in the stent
      versus UB group. Perioperative mortality rate was 18% (5/27) in the stent group
      and 13% (3/23) in the UB group. Median survival time was shorter in the stent
      versus UB group. Stent placement was associated with a greater risk of lower
      urinary tract-related signs, such as hematuria (52% [14/27]) and pollakiuria or
      stranguria (48% [13/27]). The risk of device occlusion was also greater in the
      stent (26% [7/27]) versus UB (4% [1/23]) group. The percentage of cats requiring
      additional procedures to treat complications was greater in the stent (44%;
      complications included uroabdomen, stent occlusion, and refractory cystitis)
      versus UB (9%; complications included UB occlusion and urethral obstruction)
      group. CONCLUSIONS AND CLINICAL RELEVANCE Although the benefits of stent
      placement in the treatment of ureteral obstruction in cats have been established,
      results suggested that cats treated with UB devices had a lower risk of
      complications and a longer survival time than those treated with double-pigtail
      ureteral stents.

PMID- 28763284
TI  - Comment from the Editor-in-Chief on the Letter to the Editor from Larry Janssen
      and Roy Mckay representing the AIHA Respiratory Protection Committee.

PMID- 28763283
TI  - Pathology in Practice. Aspiration pneumonia.

PMID- 28763285
TI  - Respirator performance terminology.

PMID- 28763286
TI  - Ionizing Radiation Enhances Breast Tumor Cell Migration In Vitro.
AB  - In preclinical studies, several tumor cell lines have demonstrated an epithelial
      to-mesenchymal (EMT)-dependent enhancement in migration when exposed to ionizing
      radiation at doses of 10 Gy or higher. The goal of this study was to determine
      whether a lower dose (2.3 Gy) of radiation enhances breast tumor cell migration,
      and to elucidate the potential contribution of EMT and pro-migratory secreted
      factors in radiation-induced tumor cell migration. Three human breast cancer cell
      lines were irradiated and imaged in real-time over 72 h to quantify changes in
      single cell migration, chemotactic migration and invasion. EMT markers were
      assessed and conditioned media from irradiated cells was used to determine
      whether cellular migration was influenced by secreted factors. We observed that a
      2.3 Gy dose of radiation did not induce EMT in epithelial-like MCF-7 cells and
      did not increase the ability of MCF-7 cells or highly motile MDA-MB-231 LM2-4
      cells to migrate. In addition, a 2.3 Gy dose significantly increased MDA-MB-231
      migration, as detected by single cell tracking and transwell migration assays,
      but did not increase invasion of MDA-MB-231 cells through reconstituted basement
      membrane. Cells from all three cell lines migrated further from their point of
      origin after irradiation, suggesting the cells may be responding to soluble
      factors produced by other irradiated cells. Consistently, conditioned media
      derived from 2.3 Gy irradiated MDA-MB-231 cells contained increased levels of
      several pro-migratory chemokines, and conditioned media from irradiated cells
      enhanced the migration of nonirradiated MDA-MB-231 cells. These findings indicate
      that 2.3 Gy dose of radiation is sufficient to increase migration of MDA-MB-231
      cells and to alter the single cell migration behavior of three human breast
      cancer cell lines. Our data suggest the involvement of soluble factors released
      by 2.3 Gy irradiated cells, and support further in vitro and in vivo studies to
      identify potential therapeutic targets to prevent tumor cell migration after
      irradiation.

PMID- 28763287
TI  - Role of NADPH Oxidase as a Mediator of Oxidative Damage in Low-Dose Irradiated
      and Hindlimb-Unloaded Mice.
AB  - The purpose of this study was to determine whether nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase-derived stress can account for unloading-
      and radiation-induced endothelial damage and neurovascular remodeling in a mouse
      model. Wild-type (WT, Nox2+/+) C57BL/6 mice or Nox2-/- (B6.129S6-CYBBM) knockout
      (KO) mice were placed into one of the following groups: age-matched control;
      hindlimb unloading (HLU); low-dose/low-dose-rate radiation (LDR); or HLU with LDR
      simultaneously for 21 days. The mice were then sacrificed one month later. Anti
      orthostatic tail suspension was used to model the unloading, fluid shift and
      physiological stress aspects of microgravity. The LDR was delivered using 57Co
      plates (0.04 Gy at 0.01 cGy/h) to the simulate whole-body irradiation, similar to
      that experienced while in space. Brains were isolated for characterization of
      various oxidative stress markers and vascular topology. The level of 4
      hydroxynonenal (4-HNE) protein, a specific marker for lipid peroxidation, was
      measured. Expression of aquaporin-4 (AQP4), a water channel protein expressed in
      astrocyte end-feet, was quantified. Thirty days after simulated spaceflight, KO
      mice showed decreased apoptosis (P < 0.05) in the brain compared to WT
      counterparts. The HLU-dependent increase in apoptosis in WT mice was not observed
      in KO mice. The level of 4-HNE protein was significantly elevated in the
      hippocampus of the LDR with HLU treatment group compared to WT controls (P <
      0.05). However, there were no significant differences among groups of Nox2-KO
      mice at the one-month time point. In contrast to findings in the WT animals,
      superoxide dismutase (SOD) level and expression of AQP4 were similar among all KO
      groups. In summary, for most of the parameters, the oxidative response to HLU and
      LDR was suppressed in Nox2-KO mice. This suggests that Nox2-containing NADPH
      oxidase may contribute to spaceflight environment-induced oxidative stress.

PMID- 28763288
TI  - Particle size distribution: A key factor in estimating powder dustiness.
AB  - A wide variety of raw materials, involving more than 20 samples of quartzes,
      feldspars, nephelines, carbonates, dolomites, sands, zircons, and alumina, were
      selected and characterised. Dustiness, i.e., a materials' tendency to generate
      dust on handling, was determined using the continuous drop method. These raw
      materials were selected to encompass a wide range of particle sizes (1.6-294 um)
      and true densities (2650-4680 kg/m3). The dustiness of the raw materials, i.e.,
      their tendency to generate dust on handling, was determined using the continuous
      drop method. The influence of some key material parameters (particle size
      distribution, flowability, and specific surface area) on dustiness was assessed.
      In this regard, dustiness was found to be significantly affected by particle size
      distribution. Data analysis enabled development of a model for predicting the
      dustiness of the studied materials, assuming that dustiness depended on the
      particle fraction susceptible to emission and on the bulk material's
      susceptibility to release these particles. On the one hand, the developed model
      allows the dustiness mechanisms to be better understood. In this regard, it may
      be noted that relative emission increased with mean particle size. However, this
      did not necessarily imply that dustiness did, because dustiness also depended on
      the fraction of particles susceptible to be emitted. On the other hand, the
      developed model enables dustiness to be estimated using just the particle size
      distribution data. The quality of the fits was quite good and the fact that only
      particle size distribution data are needed facilitates industrial application,
      since these data are usually known by raw materials managers, thus making
      additional tests unnecessary. This model may therefore be deemed a key tool in
      drawing up efficient preventive and/or corrective measures to reduce dust
      emissions during bulk powder processing, both inside and outside industrial
      facilities. It is recommended, however, to use the developed model only if
      particle size, true density, moisture content, and shape lie within the studied
      ranges.

PMID- 28763289
TI  - Improved hearing protector attenuation through the use of a lubricant.
AB  - A study of 40 novice hearing protection users was conducted to determine if the
      use of a lubricant with hearing protective plugs would enhance their attenuation.
      Three types of hearing protection devices (i.e., earplugs) were evaluated: roll
      down PVC foam, mushroom-style polyurethane foam, and elastomeric flanged. For
      each earplug type, the right and left ear (dry and lubricated, respectively)
      personal attenuation rating was determined using a commercially available
      microphone in real-ear apparatus. Earplug efficacy was observed to increase in
      the presence of a lubricant for all 3 plug types, with average mean elevations by
      earplug type ranging from 1.5-5.1 dB. Two of three earplug types saw
      statistically significant improvements when used with lubrication, demonstrating
      heightened mean personal attenuation ratings of 2.8 dB and 5.1 dB. The issues of
      handedness and gender differences (vis a vis ear canal size) are explored, and
      the importance of proper fitting is discussed in detail. Several specific
      questions yet to be answered are posed, and directions for further research
      indicated.

PMID- 28763290
TI  - Powered air-purifying respirator use in healthcare: Effects on thermal sensations
      and comfort.
AB  - Twelve subjects wore an N95 filtering facepiece respirator (N95 FFR), one tight
      fitting full facepiece powered air-purifying respirator (PAPR), two loose-fitting
      PAPRs, and one elastomeric/PAPR hybrid for 1 hr each during treadmill walking at
      5.6 km/hr while undergoing physiological and subjective response monitoring. No
      significant interaction (p >= .05) was noted between the five respirators in
      heart rate, respiratory rate, oxygen saturation, transcutaneous carbon dioxide,
      and perceptions of breathing effort or discomfort, exertion, facial heat, and
      overall body heat. Respirator deadspace heat/humidity were significantly greater
      for the N95 FFR, whereas tympanic forehead skin temperatures were significantly
      greater for the hybrid PAPR. Temperature of the facial skin covered by the
      respirator was equivalent for the N95 FFR and hybrid PAPR, and both were
      significantly higher than for the other three PAPRs. Perception of eye dryness
      was significantly greater for a tight-fitting full facepiece PAPR than the N95
      FFR and hybrid PAPR. At a low-moderate work rate over 1 hr, effects on
      cardiopulmonary variables, breathing perceptions, and facial and overall body
      heat perceptions did not differ significantly between the four PAPRs and a N95
      FFR, but the tight-fitting, full facepiece PAPR increased perceptions of eye
      dryness. The two loose-fitting PAPRs and the full facepiece tight-fitting PAPR
      ameliorated exercise-induced increases in facial temperature, but this did not
      translate to improved perception of facial heat and overall body heat.

PMID- 28763291
TI  - Manikin-based size-resolved penetrations of CE-marked filtering facepiece
      respirators.
AB  - The purpose of this manikin-based study was to determine the percentage
      penetrations of nine CE-marked filtering facepiece respirator models (two samples
      from each) from filtering classes FFP1, FFP2, and FFP3 and to demonstrate by an
      independent measurement method the disadvantages and shortcomings of the
      currently valid European Norm (EN 149:2001) for filtering facepieces. All of the
      filtering facepieces were evaluated size-selectively in an experimental chamber
      using charge-neutralized monodisperse ammonium sulfate in 9 sizes ranging from 20
      400 nm of count median diameter (CMD) under flowrate of 95 L/min. The results
      were then compared to the previous study concerning penetrations of 47-mm
      diameter filters cut from the filtering material of identical filtering
      facepieces. Although these two experimental methods for measuring penetrations of
      filtering materials from filtering facepieces are in good agreement (R2 = 0.91),
      the results show within-respirator variations in all three filtering classes (5.5
      19.3% for all FFRs in FFP1, 2.8-8.5% in FFP2, and 0.1-2.8% in FFP3). The most
      penetrating particle size (MPPS) in this study was found to be in the range of 25
      65 nm (CMD), which is in agreement with the range of 30-60 nm found in the
      previous study. Moreover, 7 out of 9 FFR models reached higher penetrations from
      manikin-based respirator measurements than during measurements of filters from
      the respective respirators. Furthermore, penetration levels increased up to ~50%
      when the respirator was not sealed around the face of the manikin, indicating
      that the real protection level provided by these filtering facepieces may be even
      lower if the respirator does not fit perfectly. Considering that poor filtration
      efficiency and poor fit may increase under real work conditions, the particle
      penetration is even higher than was found in this study. Therefore, the CE-marked
      respirators examined in this study may not be efficient in providing the expected
      level of protection for workers exposed to nanoparticles.

PMID- 28763292
TI  - Quantifying the dynamics of electroencephalographic (EEG) signals to distinguish
      alcoholic and non-alcoholic subjects using an MSE based K-d tree algorithm.
AB  - In this paper, we have employed K-d tree algorithmic based multiscale entropy
      analysis (MSE) to distinguish alcoholic subjects from non-alcoholic ones.
      Traditional MSE techniques have been used in many applications to quantify the
      dynamics of physiological time series at multiple temporal scales. However, this
      algorithm requires O(N2), i.e. exponential time and space complexity which is
      inefficient for long-term correlations and online application purposes. In the
      current study, we have employed a recently developed K-d tree approach to compute
      the entropy at multiple temporal scales. The probability function in the entropy
      term was converted into an orthogonal range. This study aims to quantify the
      dynamics of the electroencephalogram (EEG) signals to distinguish the alcoholic
      subjects from control subjects, by inspecting various coarse grained sequences
      formed at different time scales, using traditional MSE and comparing the results
      with fast MSE (fMSE). The performance was also measured in terms of specificity,
      sensitivity, total accuracy and receiver operating characteristics (ROC). Our
      findings show that fMSE, with a K-d tree algorithmic approach, improves the
      reliability of the entropy estimation in comparison with the traditional MSE.
      Moreover, this new technique is more promising to characterize the physiological
      changes having an affect at multiple time scales.

PMID- 28763293
TI  - Next generation sequencing and immuno-histochemistry profiling identify numerous
      biomarkers for personalized therapy of endometrioid endometrial carcinoma.

PMID- 28763294
TI  - Prevalence and causes of abnormal PSA recovery.
AB  - BACKGROUND: Prostate-specific antigen (PSA) test is of paramount importance as a
      diagnostic tool for the detection and monitoring of patients with prostate
      cancer. In the presence of interfering factors such as heterophilic antibodies or
      anti-PSA antibodies the PSA test can yield significantly falsified results. The
      prevalence of these factors is unknown. METHODS: We determined the recovery of
      PSA concentrations diluting patient samples with a standard serum of known PSA
      concentration. Based on the frequency distribution of recoveries in a pre-study
      on 268 samples, samples with recoveries <80% or >120% were defined as suspect, re
      tested and further characterized to identify the cause of interference. RESULTS:
      A total of 1158 consecutive serum samples were analyzed. Four samples (0.3%)
      showed reproducibly disturbed recoveries of 10%, 68%, 166% and 4441%. In three
      samples heterophilic antibodies were identified as the probable cause, in the
      fourth anti-PSA-autoantibodies. The very low recovery caused by the latter
      interference was confirmed in serum, as well as heparin- and EDTA plasma of blood
      samples obtained 6 months later. Analysis by eight different immunoassays showed
      recoveries ranging between <10% and 80%. In a follow-up study of 212 random
      plasma samples we found seven samples with autoantibodies against PSA which
      however did not show any disturbed PSA recovery. CONCLUSIONS: About 0.3% of PSA
      determinations by the electrochemiluminescence assay (ECLIA) of Roche diagnostics
      are disturbed by heterophilic or anti-PSA autoantibodies. Although they are rare,
      these interferences can cause relevant misinterpretations of a PSA test result.

PMID- 28763295
TI  - Contamination of dried blood spots - an underestimated risk in newborn screening.
AB  - BACKGROUND: Newborn screening (NBS) is an established screening procedure in many
      countries worldwide, aiming at the early detection of inborn errors of
      metabolism. For decades, dried blood spots have been the standard specimen for
      NBS. The procedure of blood collection is well described and standardized and
      includes many critical pre-analytical steps. We examined the impact of
      contamination of some anticipated common substances on NBS results obtained from
      dry spot samples. This possible pre-analytical source of uncertainty has been
      poorly examined in the past. METHODS: Capillary blood was obtained from 15 adult
      volunteers and applied to 10 screening filter papers per volunteer. Nine filter
      papers were contaminated without visible trace. The contaminants were baby diaper
      rash cream, baby wet wipes, disinfectant, liquid infant formula, liquid infant
      formula hypoallergenic (HA), ultrasonic gel, breast milk, feces, and urine. The
      differences between control and contaminated samples were evaluated for 45 NBS
      quantities. We estimated if the contaminations might lead to false-positive NBS
      results. RESULTS: Eight of nine investigated contaminants significantly altered
      NBS analyte concentrations and potentially caused false-positive screening
      outcomes. A contamination with feces was most influential, affecting 24 of 45
      tested analytes followed by liquid infant formula (HA) and urine, affecting 19
      and 13 of 45 analytes, respectively. CONCLUSIONS: A contamination of filter paper
      samples can have a substantial effect on the NBS results. Our results underline
      the importance of good pre-analytical training to make the staff aware of the
      threat and ensure reliable screening results.

PMID- 28763296
TI  - Hair testing of GHB: an everlasting issue in forensic toxicology.
AB  - BACKGROUND: In this paper, the authors present a critical review of different
      studies regarding hair testing of endogenous gamma-hydroxybutyrate (GHB),
      concentrations in chronic users, and values measured after a single GHB exposure
      in drug facilitated sexual assault (DFSA) cases together with the role of a
      recently identified GHB metabolite, GHB-glucuronide. CONTENT: The following
      databases (up to March 2017) PubMed, Scopus and Web of Science were used,
      searching the following key words: gamma-hydroxybutyrate, GHB, GHB glucuronide,
      hair. The main key words "GHB" and "gamma-hydroxybutyrate" were searched
      singularly and then associated individually to each of the other keywords.
      SUMMARY: Of the 2304 sources found, only 20 were considered appropriate for the
      purpose of this paper. Summing up all the studies investigating endogenous GHB
      concentration in hair, a very broad concentration range from 0 to 12 ng/mg was
      found. In order to detect a single GHB dose in hair it is necessary to commonly
      wait 1 month for collecting hair and a segmental analysis of 3 or 5 mm fragments
      and the calculation of a ratio between the targeted segment and the others
      represent a reliable method to detect a single GHB intake considering that the
      ratios presently proposed vary from 3 and 10. The only two studies so far
      performed, investigating GHB-Glucuronide in hair, show that the latter does not
      seem to provide any diagnostic information regarding GHB exposure. OUTLOOK: A
      practical operative protocol is proposed to be applied in all suspected cases of
      GHB-facilitated sexual assault (GHB-FSA).

PMID- 28763297
TI  - Adiponectin and leptin as first trimester markers for gestational diabetes
      mellitus: a cohort study.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is increasing partly due to the
      obesity epidemic. Adipocytokines have thus been suggested as first trimester
      screening markers for GDM. In this study we explore the associations between body
      mass index (BMI) and serum concentrations of adiponectin, leptin, and the
      adiponectin/leptin ratio. Furthermore, we investigate whether these markers can
      improve the ability to screen for GDM in the first trimester. METHODS: A cohort
      study in which serum adiponectin and leptin were measured between gestational
      weeks 6+0 and 14+0 in 2590 pregnant women, categorized into normal weight,
      moderately obese, or severely obese. RESULTS: Lower concentrations of adiponectin
      were associated with GDM in all BMI groups; the association was more pronounced
      in BMI<35 kg/m2 (p=0.30 for interaction). Leptin was inversely associated with
      GDM in severely obese (p=0.033), but showed no association in women with BMI<35
      kg/m2. The adiponectin/leptin ratio was associated with GDM in women with BMI<35
      kg/m2 but not in severely obese women (p=0.79). In regard to predicting GDM,
      maternal characteristics combined with adiponectin alone, adiponcetin and leptin,
      and adiponcetin/leptin ratio had the strongest associations in women with BMI<35
      kg/m2. These models had a detection rate of 77.3%-80.3% when the false positive
      rate was fixed at 25%. CONCLUSIONS: Low adiponectin measured in the first
      trimester is associated with the development of GDM; higher BMI was associated
      with lower performance of adiponectin, though this was insignificant. Leptin had
      an inverse relationship with GDM in severely obese women and did not improve the
      ability to predict GDM.

PMID- 28763298
TI  - Interference between ethosuximide and barbiturates in an immunochromatographic
      method.

PMID- 28763299
TI  - False negative results caused by erroneous automated result interpretation
      algorithm on the FilmArray 2.0 instrument.

PMID- 28763300
TI  - Ablation of adipose-HO-1 expression increases white fat over beige fat through
      inhibition of mitochondrial fusion and of PGC1alpha in female mice.
AB  - Background Hmox1 plays an important role in the regulation of mitochondrial
      bioenergetics and function by regulating cellular heme-derived CO and bilirubin.
      Previous studies have demonstrated that global disruption of HO-1 in humans and
      mice resulted in severe organ dysfunction. Methods We investigated the potential
      role of adipose-specific-HO-1 genetic ablation on adipose tissue function,
      mitochondrial quality control and energy expenditure by generating an adipo-HO-1
      knockout mouse model (Adipo-HO-1-/-) and, in vitro, adipocyte cells in which HO
      activity was inhibited. Adiposity, signaling proteins, fasting glucose and oxygen
      consumption were determined and compared to adipocyte cultures with depressed
      levels of both HO-1/HO-2. Results Adipo-HO-1-/- female mice exhibited increased
      adipocyte size, and decreases in the mitochondrial fusion to fission ratio, PGC1,
      and SIRT3. Importantly, ablation of HO-1 in adipose tissue resulted in fat
      acquiring many properties of visceral fat such as decreases in thermogenic genes
      including pAMPK and PRDM16. Deletion of HO-1 in mouse adipose tissue led to
      complete metabolic dysfunction, an increase in white adipose tissue, a reduction
      of beige fat and associated increases in FAS, aP2 and hyperglycemia.
      Mechanistically, genetic deletion of HO-1 in adipose tissues decreased the
      mitochondrial fusion to fission ratio; disrupted the activity of the PGC1
      transcriptional axis and thermogenic genes both in vitro and in vivo. Conclusion
      Ablation of adipose tissue-HO-1 abridged PGC1 expression promoted mitochondrial
      dysfunction and contributed to an increase of pro-inflammatory visceral fat and
      abrogated beige-cell like phenotype.

PMID- 28763301
TI  - Application of povidone-iodine at delivery significantly increases maternal
      urinary iodine but not neonatal thyrotropin in an area with iodine sufficiency.
AB  - BACKGROUND: The aim of the present study was to investigate the effect of
      povidone-iodine (PVP-I) application at delivery on maternal urinary iodine
      concentration (UIC) and neonatal thyrotropin concentration. METHODS: In this
      cross-sectional study, urine samples were collected from each pregnant woman
      after admission to the hospital and before routine application of the PVP-I for
      delivery preparation and after delivery at time of screening for congenital
      hypothyroidism. A heel-prick blood sample was taken from all newborns. RESULTS: A
      total of 394 pregnant women at time of delivery participated in this study.
      Median (interquartile range [IQR]) maternal UIC values were 120 (105-157) and 253
      (126-470) MUg/L before and after delivery, respectively (p<0.001). No significant
      correlations were observed between maternal UIC before and after delivery and
      neonatal thyrotropin levels. CONCLUSIONS: Application of PVP-I significantly
      increased UIC in postpartum mothers; however, thyrotropin concentration in
      neonates, whose mothers had adequate UIC, was within the normal range.

PMID- 28763302
TI  - Intramuscularly injected neurotropin reduced muscular mechanical hyperalgesia
      induced by repeated cold stress in rats.
AB  - An extract of rabbit skin inflamed by inoculation with the vaccinia virus,
      neurotropin [by intravenous, oral, and intramuscular (i.m.) administration], has
      been used in China and Japan for the treatment of chronic pain. In this study, we
      investigated the analgesic mechanism of i.m. neurotropin. Rats were exposed to
      repeated cold stress, and muscular mechanical hyperalgesia was evaluated by
      measuring the withdrawal threshold of the gastrocnemius muscle using Randall
      Selitto apparatus. I.m. but not subcutaneous, neurotropin dose dependently
      reduced the repeated cold stress-induced muscular mechanical hyperalgesia for 3
      h, but it had no effect in normal rats. Injections of neurotropin into the right
      gastrocnemius, quadriceps femoris, biceps brachii, and trapezius muscles reduced
      the muscular mechanical hyperalgesia of the gastrocnemius muscle bilaterally.
      Intrathecal administration of antagonists to GABAergic, serotonergic, and
      cholinergic receptors, but not alpha2-adrenergic receptors, and intraperitoneal
      administration of opioid receptor antagonist inhibited the analgesic effect of
      neurotropin. These results indicated that an i.m. injection of neurotropin
      induced long-lasting wide-spread bilateral muscular analgesia by activating
      spinal serotonergic and GABAergic receptors. As distinct from analgesia by
      systemic administration, spinal cholinergic and opioidergic, but not adrenergic
      receptors, are also involved. The present study supports the effectiveness of
      neurotropin treatment for muscular mechanical hyperalgesia.

PMID- 28763303
TI  - Insights into the potential antidepressant mechanisms of cilostazol in
      chronically restraint rats: impact on the Nrf2 pathway.
AB  - Ample evidence has pointed to a close link between oxidative stress,
      mitochondrial dysfunction, and depression. Nuclear factor-erythroid 2-related
      factor-2 (Nrf2) is a master regulator of cellular redox homeostasis and affects
      mitochondrial function. Nrf2 holds promise for depression prevention and
      treatment. This study aimed to investigate the potential prophylactic
      antidepressant effect of cilostazol and the contribution of the Nrf2 pathway
      toward the putative neuroprotection. The behavioral and neurochemical effects of
      concomitant treatment of oral cilostazol at doses of 7.5, 15, and 30 mg/kg/day in
      Wistar rats exposed to chronic restraint stress (CRS) for 4 weeks were assayed.
      Cilostazol prevented CRS-induced depressive-like behavior shown in sucrose
      preference, forced-swimming, and open-field tests, and hypothalamus-pituitary
      adrenal axis hyperactivity (adrenal gland weight and serum corticosterone).
      Cilostazol prevented CRS-induced increase in hippocampal lipid peroxidation and 8
      hydroxy-2'-deoxyguanosine, and a decrease in antioxidant activities (glutathione
      level, superoxide dismutase, and catalase). Western blot and PCR showed that
      cilostazol favorably modulated the Nrf2 protein and heme oxygenase-1 and NAD(P)H:
      quinone oxidoreductase-1 gene expression in the hippocampus of CRS rats.
      Cilostazol also prevented the decrease in the hippocampal activities of
      mitochondrial respiratory enzyme complexes I-IV. These behavioral and biochemical
      findings indicated the potential prophylactic antidepressant effect and mechanism
      of cilostazol by preventing oxidative stress by activation of redox defense
      mechanisms mediated through the Nrf2 pathway and restoring mitochondrial
      dysfunction.

PMID- 28763304
TI  - Chronic inflammatory demyelinating polyneuropathy.
AB  - PURPOSE OF REVIEW: As a syndrome with typical and atypical cases, chronic
      inflammatory demyelinating polyneuropathy (CIDP) has been a difficult disorder to
      diagnose and treat. The pathophysiologic basis for CIDP has not been established,
      contributing to the challenges in dealing with these patients. However, as one of
      only a handful of treatable peripheral neuropathies, there has been a tendency to
      diagnose CIDP to attempt a therapeutic intervention. We are also aware that there
      has also been overtreatment of some patients. This combination of overdiagnosis
      and prolonged treatment has been a concern. This chapter will review these
      challenges and discuss recent findings that will lead to improved diagnosis and
      treatment. RECENT FINDINGS: The factors leading to misdiagnosis of CIDP were
      explored in a cohort of patients referred to a neuromuscular center. On a more
      positive note, the identification of two disorders with antibodies directed at
      paranodal constituents has excited the field. Treatment options have increased
      and been clarified. Pulse corticosteroids have been compared with oral prednisone
      and with intravenous immunoglobulin. The clinical trial of subcutaneous
      immunoglobulin in CIDP has shown both efficacy and a very low side effect profile
      adding to our therapeutic options. SUMMARY: The current review will identify
      recent developments that show both the challenges and the exciting growth in our
      ability to diagnose and treat CIDP.

PMID- 28763305
TI  - Update on diagnostics of metabolic myopathies.
AB  - PURPOSE OF REVIEW: This review aims to highlight the most relevant clinical and
      laboratory findings, regarding acute and progressive metabolic myopathies, and to
      develop an algorithm addressing clinicians to clinical practice. RECENT FINDINGS:
      Although diagnosis of metabolic myopathies remains still challenging, the recent
      identification of new disorders has increased the number of patients requiring
      specific investigations. Nowadays, a more detailed characterization of the
      clinical spectrum of metabolic myopathies improved awareness as well as a deeper
      knowledge on their natural history or multisystem involvement. Diagnostic
      procedures, as first-line screening tests are necessary for an earlier and more
      accurate diagnostic work up, not only in infantile cases, but also in adults with
      suspected metabolic myopathies. New generation diagnostic techniques such as NGS
      (Next Generation Sequencing) and whole exome/genome sequencing have emerged as
      innovative tools to extensively evaluate either known genes variants or new
      candidate genes as possible causes of metabolic myopathies. SUMMARY: Diagnosis of
      metabolic myopathies is still challenging for clinicians because of rarity and
      clinical heterogeneity which is often overlapping with other neuromuscular
      disorders. Detailed algorithms supported by advanced laboratory investigations
      may be helpful to timely reach a diagnosis, so allowing an earlier therapeutic
      decision.

PMID- 28763306
TI  - Efficacy and Safety of Proton Pump Inhibitors in the Long-Term Aspirin Users: A
      Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Long-term aspirin use in cardiovascular disease prevention may result
      in gastrointestinal bleeding. Although proton pump inhibitors (PPI) have been
      shown to reduce the risks of peptic ulcers and dyspeptic symptoms in long-term
      aspirin users in the randomized controlled trials, there are safety concerns
      about the long-term use of PPI. STUDY QUESTION: What is the safety and efficacy
      of PPI in patients using aspirin in long term for prevention of cardiovascular
      diseases and stroke? METHODS: We searched MEDLINE, EMBASE, CENTRAL, CINAHL,
      ProQuest, and relevant references from inception through February 2015, and used
      random-effects model for meta-analysis. RESULTS: A total of 10 publications from
      9 studies (n = 6382) were included in the meta-analysis. Compared with control,
      PPI reduced the risks of peptic ulcers [risk ratio (RR): 0.19; 95% confidence
      interval: 0.13-0.26; P < 0.00001], gastric ulcers [0.24 (0.16-0.35); P <
      0.00001], duodenal ulcers [0.12 (0.05-0.29); P < 0.00001], bleeding ulcers [0.22
      (0.10-0.51); P = 0.0004], and erosive esophagitis [0.14 (0.07-0.28); P <
      0.00001]. PPI increased the resolution of epigastric pain [1.13 (1.03-1.25); P =
      0.01], heartburn [1.24 (1.18-1.31); P < 0.00001], and regurgitation [1.26 (1.13
      1.40); P < 0.0001], but did not increase the risks of all-cause mortality [1.72
      (0.61-4.87); P = 0.31], cardiovascular mortality [1.80 (0.59-5.44); P = 0.30],
      nonfatal myocardial infarction/ischemia [0.56 (0.22-1.41); P = 0.22], ischemic
      stroke/transient ischemic attack [1.09 (0.34-3.53); P = 0.89] and other adverse
      events. CONCLUSIONS: The PPI seems to be effective in preventing peptic ulcers
      and erosive esophagitis and in resolution of dyspeptic symptoms without
      increasing adverse events, cardiac risks or mortality in long-term aspirin users.

PMID- 28763308
TI  - Revascularization strategies and in-hospital management in acute coronary
      syndromes complicated by hemophilia A or hemophilia B.
AB  - : Among adult patients with hemophilia A and hemophilia B the emergent management
      of acute coronary syndromes (ACSs) is challenging, and exposure to antithrombotic
      agents and/or revascularization procedures may confer an enhanced risk of
      bleeding. We sought to identify clinical characteristics and in-hospital outcomes
      among ACS patients with hemophilia A/hemophilia B, compared with matched
      noncoagulopathic ACS controls. Case discharges from the Nationwide Inpatient
      Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research
      and Quality (1998-2011) had International Classification of Diseases, 9th
      Revision codes for hemophilia A/hemophilia B and ACS. Control discharges were
      matched to cases by year of discharge and hospital. Discharges in both groups
      were assessed for cardiovascular risk factors, type of ACS, use of coronary
      artery bypass grafting, percutaneous coronary intervention (PCI), bare-metal
      stent and/or drug-eluting stent, bleeding, and death. In total, 237 cases and 148
      848 matched controls were identified. Among cases, HIV/Hepatitis C positivity was
      more common and obesity/hyperlipidemia less common. ST-elevation myocardial
      infarction (STEMI) occurred less frequently among hemophilia A cases than
      controls. hemophilia A and hemophilia B cases were more likely to be managed
      medically. Cases treated with coronary stent placement were more likely to
      receive a bare-metal stent than controls. Among PCI, bleeding was more common
      among hemophilia A cases. The death rates were comparable between groups. ACS
      hemophilia A/hemophilia B cases were more often treated noninvasively compared
      with controls, suggesting an avoidance of PCI/coronary artery bypass grafting in
      this population, and bleeding (among hemophilia A) was more common. These
      findings support further study of the management of ACS and in-hospital outcomes
      among individuals with hemophilia.

PMID- 28763307
TI  - Comparison of 3-Factor Versus 4-Factor Prothrombin Complex Concentrate With
      Regard to Warfarin Reversal, Blood Product Use, and Costs.
AB  - BACKGROUND: Prothrombin complex concentrates (PCCs) are drug products containing
      varying amounts of vitamin K-dependent coagulation factors II, VII, IX, and X.
      The evidence comparing 3-factor PCC (3-PCC) versus 4-factor PCC (4-PCC) for
      warfarin reversal is conflicting. It has been hypothesized that 3-PCC may be less
      effective than 4-PCC because of relatively lower factor VII content. STUDY
      QUESTION: The primary objective of this study was to compare international
      normalized ratio (INR) reversal between 3-PCC and 4-factor PCC (4-PCC) in
      warfarin-treated patients. The secondary objectives include comparing blood
      product use, total reversal costs, and cost-effectiveness between the groups.
      STUDY DESIGN: This was a retrospective cohort study conducted in 2 affiliated,
      academic institutions in the United States. Consecutive adult patients who
      received 3-PCC or 4-PCC for warfarin reversal were included. MEASURES AND
      OUTCOMES: The primary outcome was adequate INR reversal defined as a final INR
      <=1.5. Secondary outcomes were the utilization of plasma, red blood cells and
      platelets, reversal costs, and the cost-effectiveness ratio. RESULTS: There were
      89 patients who were included in the overall cohort (3-PCC = 57, 4-PCC = 32).
      Adequate INR reversal occurred less commonly with 3-PCC (45.6%) compared with 4
      PCC (87.5%) (P < 0.001). There was no significant difference in the proportion of
      patients who received plasma (32% vs. 28%, P = 0.813), red blood cells (37% vs.
      47%, P = 0.377), or platelets (16% vs. 28%, P = 0.180) between the 3-PCC and 4
      PCC groups, respectively. The median reversal cost of 3-PCC ($3663) was lower
      than 4-PCC ($5105) (P = 0.001). The cost-effective ratio favored 4-PCC
      ($5105/87.5% = $5834) compared with 3-PCC ($3663/45.6% = $8033). CONCLUSIONS:
      Four-PCC was more effective than 3-PCC with regard to INR reversal in patients
      taking warfarin, but blood product use was similar. Although 4-PCC is associated
      with increased reversal costs, it may be cost-effective in terms of INR reversal.

PMID- 28763309
TI  - Clinical characteristics, risk factors, and outcomes of usual and unusual site
      venous thromboembolism.
AB  - : The primary objective was to demonstrate the different risk factors among
      patients presenting with usual and unusual site venous thromboembolism (VTE). The
      secondary objectives were to compare clinical characteristics and outcomes in
      each group. This was a retrospective observational cohort study. Patients
      admitted in Chiang Mai University Hospital who were diagnosed with VTE during
      January 2010 through December 2012 were included and classified into two groups:
      the usual and unusual site VTE. The usual sites of VTE included pulmonary
      embolism and lower extremity deep vein thrombosis. Clinical characteristics, risk
      factors, treatment, recurrence, bleeding rates, and deaths were collected. There
      were 165 patients included in the study, 82 in usual site group and 83 in unusual
      site group. Patients in usual site group were older than unusual site group (mean
      58 vs. 50 years, P = 0.003) and were more symptomatic (89 vs. 49.4%, P < 0.001).
      The higher proportion of patients in usual site group had prolonged
      immobilization (22.0 vs. 2.4%, P < 0.001), prior surgery (12.2 vs. 1.2%, P =
      0.005), and a history of chemotherapy (25.6 vs. 3.6%, P < 0.001). Local
      inflammation was significantly more common in unusual site group (0 vs. 8.5%, P <
      0.001). The recurrent VTE and major bleeding rates were not statistically
      different between groups. The 3-year mortality rate was significantly higher in
      usual site VTE group (73.1 vs. 57.8%, P = 0.049). The study revealed the
      different risk factors and clinical characteristics between usual and unusual VTE
      sites.

PMID- 28763310
TI  - Elderly patients with multiple myeloma: towards a frailty approach?
AB  - PURPOSE OF REVIEW: To describe how to better identify frail multiple myeloma
      patients and to treat them appropriately. RECENT FINDINGS: Proteasome inhibitors,
      such as bortezomib, carfilzomib, and ixazomib, and immunomodulatory agents
      (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, have significantly
      improved the outcome of multiple myeloma patients in the last decade. However,
      both in clinical trials and in daily clinical practice, elderly multiple myeloma
      patients have shown lesser benefit. This is mainly due to less stringent use of
      proteasome inhibitors and IMiDs, increased toxicity, and subsequent early
      discontinuation of therapy in elderly. SUMMARY: Multiple myeloma typically
      affects elderly patients. Approximately one-third of patients are older than 75
      years at diagnosis. Moreover, at least 30% are frail, both due to disease-related
      symptoms and (age-related) decline in physical capacity, presence of
      comorbidities, frailty, polypharmacy, nutritional status, and cognitive
      impairment. Treatment regimens that are investigated in clinical trials for
      transplant-ineligible patients have largely been investigated in fit, rather than
      frail patients, the latter being typically excluded or highly underrepresented
      therein. Data on the feasibility and efficacy of current standards of care are
      therefore lacking in frail patients. Preliminary data suggest a higher toxicity
      and discontinuation rate, loss of efficacy, and impaired quality of life in frail
      patients. Geriatric assessment helps to identify frail patients according to
      their functional and cognitive status. Both the International Myeloma Working
      Group (IMWG)-frailty index and Revised Myeloma Comorbidity Index constitute
      recently proposed algorithms that easily identify intermediate-fit and frail
      patients. Ongoing and future clinical trials, specifically designed for frail
      patients, will hopefully define frailty-directed treatment selection.

PMID- 28763311
TI  - Inter-rater reliability of two paediatric early warning score tools.
AB  - BACKGROUND: Paediatric early warning score (PEWS) assessment tools can assist
      healthcare providers in the timely detection and recognition of subtle patient
      condition changes signalling clinical deterioration. However, PEWS tools
      instrument data are only as reliable and accurate as the caregivers who obtain
      and document the parameters. OBJECTIVE: The aim of this study is to evaluate
      inter-rater reliability among nurses using PEWS systems. DESIGN: The study was
      carried out in five paediatrics departments in the Central Denmark Region. Inter
      rater reliability was investigated through parallel observations. A total of 108
      children and 69 nurses participated. Two nurses simultaneously performed a PEWS
      assessment on the same patient. Before the assessment, the two participating
      nurses drew lots to decide who would be the active observer. Intraclass
      correlation coefficient, Fleiss' kappa and Bland-Altman limits of agreement were
      used to determine inter-rater reliability. RESULTS: The intraclass correlation
      coefficients for the aggregated PEWS score of the two PEWS models were 0.98 and
      0.95, respectively. The kappa value on the individual PEWS measurements ranged
      from 0.70 to 1.0, indicating good to very good agreement. The nurses assigned the
      exact same aggregated score for both PEWS models in 76% of the cases. In 98% of
      the PEWS assessments, the aggregated PEWS scores assigned by the nurses were
      equal to or below 1 point in both models. CONCLUSION: The study showed good to
      very good inter-rater reliability in the two PEWS models used in the Central
      Denmark Region.

PMID- 28763312
TI  - 3q29 Chromosomal duplication in a neonate with associated myelomeningocele and
      midline cranial defects.

PMID- 28763314
TI  - Anaesthesiology and ethics: Presumed consent with real consequences.

PMID- 28763313
TI  - Generalizability of EXCEL and NOBLE results to a large registry population with
      unprotected left main coronary artery disease.
AB  - OBJECTIVE: The aim of this study was to determine how trial-based findings of
      EXCEL and NOBLE might be interpreted and generalizable in 'real-world' settings
      with comparison of data from the large-scaled, all-comer Interventional Research
      Incorporation Society-Left MAIN Revascularization (IRIS-MAIN) registry. PATIENTS
      AND METHODS: We compared baseline clinical and procedural characteristics and
      also determined how the relative treatment effect of percutaneous coronary
      intervention (PCI) and coronary artery bypass grafting (CABG) was different in
      EXCEL and NOBLE, compared with those of the multicenter, IRIS-MAIN registry
      (n=2481). The primary outcome for between-study comparison was a composite of
      death, myocardial infarction (MI), or stroke. RESULTS: There were between-study
      differences in patient risk profiles (age, BMI, diabetes, and clinical
      presentation), lesion complexities, and procedural characteristics (stent type,
      the use of off-pump surgery, and radial artery); the proportion of diabetes and
      acute coronary syndrome was particularly lower in NOBLE than in other studies.
      Although there was interstudy heterogeneity for the protocol definition of MI,
      the risks for serious composite outcome of death, MI, or stroke were similar
      between PCI and CABG in EXCEL [hazard ratio (HR): 1.00; 95% confidence interval
      (CI): 0.79-1.26; P=0.98] and in the matched cohort of IRIS-MAIN (HR: 1.08; 95%CI:
      0.85-1.38; P=0.53), whereas it was significantly higher after PCI than after CABG
      in NOBLE (HR: 1.47; 95%CI: 1.06-2.05; P=0.02), which was driven by more common MI
      and stroke after PCI. CONCLUSION: In the comparison of a large-sized, all-comer
      registry, the EXCEL trial might represent better generalizability with respect to
      baseline characteristics and observed clinical outcomes compared with the NOBLE
      trial.

PMID- 28763315
TI  - Efficacy and safety of buprenorphine in peripheral nerve blocks: A meta-analysis
      of randomised controlled trials.
AB  - BACKGROUND: The duration of analgesia provided by nerve blocks is limited if
      local anaesthetics are administered alone. Therefore, a variety of additives to
      local anaesthetics have been investigated to prolong postoperative analgesia
      following single-shot nerve blocks. OBJECTIVE(S): The aims of the current meta
      analysis were to assess the efficacy and safety of the addition of perineural
      buprenorphine to local anaesthetic compared with local anaesthetic alone, or
      combined with systemic administration of buprenorphine, or other perineural
      opioids for peripheral nerve blocks. DESIGN: Systematic review and meta-analysis
      of randomised controlled trials (RCTs). DATA SOURCES: The following data sources
      were systematically searched: MEDLINE, CENTRAL and EMBASE (till 03/2016).
      ELIGIBILITY CRITERIA: All RCTs focusing on the efficacy and safety of perineural
      buprenorphine combined with local anaesthetic compared with local anaesthetic
      alone, or in combination with systemic buprenorphine, or other perineural opioids
      for peripheral nerve blocks were included. RESULTS: We included 13 RCTs (685
      patients). Participants treated with perineural buprenorphine combined with local
      anaesthetic showed a longer duration of analgesia compared with those receiving
      local anaesthetic alone [mean difference 8.64 h, 95% confidence interval (CI)
      (6.44 to 10.85); P < 0.01]. However, the buprenorphine group had a significantly
      higher relative risk (RR) for postoperative nausea and vomiting (PONV) [RR 5.0,
      95% CI (1.12 to 22.27); P = 0.03]. The perineural administration of buprenorphine
      provided a longer duration of analgesia than an intramuscular application [mean
      difference 6.87 h, 95% CI (4.02 to 9.71); P < 0.01] without evidence of a
      difference in the incidence of PONV between the modes of administration [RR 0.76,
      95% CI (0.28 to 2.03); P = 0.58]. CONCLUSION: This meta-analysis revealed that
      the addition of buprenorphine to a local anaesthetic peripheral nerve block
      prolongs postoperative analgesia for about 8 h but significantly increases the
      risk for PONV. Perineural administration is more effective than systemic
      application but is associated with a similar risk of PONV. However, these results
      were influenced by heterogeneity so that further trials (especially head-to-head
      comparisons) are needed in the future. TRIAL REGISTRATION:
      PROSPERO(www.crd.york.ac.uk) identifier: CRD42016036054.

PMID- 28763316
TI  - Effects of calcium chloride coadministered with neostigmine on neuromuscular
      blockade recovery: A double-blind randomised study.
AB  - BACKGROUND: Ionised calcium plays an important role in neuromuscular
      transmission, but its effects on the reversal of nondepolarising neuromuscular
      blockade have not been fully evaluated. OBJECTIVE: We examined whether calcium
      chloride coadministered with neostigmine could enhance the rate of neuromuscular
      recovery. DESIGN: Randomised double-blind trial. SETTING: A tertiary teaching
      hospital. PATIENTS: In total, 53 patients undergoing elective surgery under
      general anaesthesia with neuromuscular monitoring by acceleromyography using a
      TOF-Watch SX monitor. INTERVENTIONS: Patients were randomly allocated to receive
      either 5 mg kg of calcium chloride (calcium group, n = 26) or the same volume of
      normal saline (control group, n = 27) coadministered with 25 MUg kg of
      neostigmine and 15 MUg kg of atropine at the end of surgery. MAIN OUTCOME
      MEASURES: The primary end point was the neuromuscular recovery time [time from
      neostigmine administration to recovery of the TOF ratio (TOFr) to 0.9]. Secondary
      end points included the TOFr at 5, 10 and 20 min after neostigmine administration
      and the incidence of postoperative residual curarisation (PORC), defined as a
      TOFr less than 0.9 at each time point. RESULTS: The neuromuscular recovery time
      was significantly faster in the calcium group than in the control group (median
      [Q1 to Q3]; 5.0 [3.0 to 7.0] vs. 6.7 [5.7 to 10.0] min, respectively; P = 0.007).
      At 5 min after neostigmine administration, the TOFr was higher [87 (74 to 100)
      vs. 68 (51 to 81)%, respectively; P = 0.002] and the incidence of PORC was lower
      (50.0 vs. 81.5%, respectively; P = 0.016) in the calcium group than in the
      control group. There were no differences between the two groups with respect to
      the TOFr or incidence of PORC at 10 and 20 min after neostigmine administration.
      CONCLUSION: Calcium chloride coadministered with neostigmine enhanced
      neuromuscular recovery in the early period of nondepolarising neuromuscular
      blockade reversal.

PMID- 28763317
TI  - Rocuronium is more hepatotoxic than succinylcholine in vitro.
AB  - BACKGROUND: The development of liver failure is a major problem in critically ill
      patients. The hepatotoxicity of many drugs, as one important reason for liver
      failure, is poorly screened for in human models. Rocuronium and succinylcholine
      are neuromuscular blocking agents used for tracheal intubation and for rapid
      sequence induction. OBJECTIVE: We used an in-vitro test with a permanent cell
      line and compared rocuronium and succinylcholine for hepatotoxicity. DESIGN: In
      vitro study. SETTING: A basic science laboratory, University Hospital Rostock,
      Germany. MATERIAL/(PATIENTS): The basic test compound is the permanent human
      liver cell line HepG2/C3A. In a standardised microtitre plate assay the toxicity
      of different concentrations of rocuronium, succinylcholine and plasma control was
      tested. INTERVENTIONS: After two incubation periods of 3 days, the viability of
      cells (XTT test, lactate dehydrogenase release and trypan blue staining), micro
      albumin synthesis and the cytochrome 1A2 activity (metabolism of ethoxyresorufin)
      were measured. MAIN OUTCOME MEASURES: Differences between rocuronium and
      succinylcholine were assessed using the Kruskal-Wallis one-way test and two
      tailed Mann-Whitney U test. RESULTS: Rocuronium, but not succinylcholine, led to
      a significant dose-dependent decrease of viability, albumin synthesis and
      cytochrome 1A2 activity of test cells. CONCLUSION: An in-vitro test with a cell
      line showed hepatotoxicity of rocuronium that was dose-dependent. Further studies
      are needed to investigate the underlying mechanisms of the effects of rocuronium
      on hepatic cellular integrity. TRIAL REGISTRATION: Not suitable.

PMID- 28763318
TI  - Plasma levels of local anaesthetic following supraclavicular block.

PMID- 28763319
TI  - Compressed air injection technique for Shamrock lumbar plexus block.

PMID- 28763320
TI  - Should the transversus abdominis plane block be performed for laparoscopic
      colorectal surgery?

PMID- 28763321
TI  - Postoperative nausea and vomiting: solutions and questions.

PMID- 28763322
TI  - Reply to: postoperative nausea and vomiting: solutions and questions.

PMID- 28763323
TI  - Risk prediction instruments in geriatric surgery are available but often ignored.

PMID- 28763324
TI  - Reply to: risk prediction instruments in geriatric surgery are available but
      often ignored.

PMID- 28763325
TI  - Could Activity Modifications Indicate Physical Decline Among Adults With
      Symptomatic Knee Osteoarthritis?
AB  - OBJECTIVES: Mobility activity modifications indicate early functional losses that
      act as precursors to future declines among community-dwelling older adults.
      However, there is scarce evidence on whether activity modifications indicate
      poorer physical health among adults with symptomatic osteoarthritis, a major
      cause of disability. Our purpose was to investigate whether patient-reported
      mobility activity modifications indicated poorer physical health among adults
      with symptomatic knee osteoarthritis. DESIGN: Secondary cross-sectional analysis
      of randomized trial data was performed. Preclinical Disability Questionnaire was
      used to group participants into the following three categories: difficulty,
      modified, and no difficulty walking/stair climbing. Kruskal Wallis and chi tests
      were used to compare clinical factors across groups. RESULTS: Among 121
      participants (median age = 60 yrs; 73% female; 60% white), less than 10% had
      modified walking/stair climbing. Compared with those with no walking difficulty,
      participants with modified walking had significantly less balance (P = 0.01) and
      global health (P = 0.01) as well as greater knee pain (P = 0.05) and physical
      disability (P = 0.04). Those with modified stair climbing had significantly
      smaller walking distances (P = 0.03) compared with those with no difficulty stair
      climbing. CONCLUSIONS: Activity modifications may signal early impairments in
      physical health among people with symptomatic knee osteoarthritis. If confirmed,
      patient-reported activity modifications may enhance symptom evaluation in
      osteoarthritis and enable a better understanding of the disablement process.

PMID- 28763326
TI  - Point-of-Care Ultrasonography Findings and Care Use Among Patients Undergoing
      Ultrasound-Guided Shoulder Injections.
AB  - OBJECTIVE: The aims of the study were to assess the overall reduction of pain in
      patients undergoing ultrasound-guided shoulder injections and to characterize the
      preinjection point-of-care ultrasound findings and use of clinical services
      postinjection including the use of magnetic resonance imaging and surgeries.
      DESIGN: Data of 172 patients who underwent ultrasound-guided subacromial
      subdeltoid injection or glenohumeral joint injection were reviewed for
      preinjection point-of-care ultrasound findings, change in pain intensity at 2 mos
      from baseline, and use of care at 6 mos' postinjection. Pain intensity was
      measured by the numeric rating scale and a dichotomous report of global
      impression of significant improvement in pain. Responders were defined as those
      with 50% or more reduction in numeric rating scale or those with global
      impression of 50% or more improvement. RESULTS: There were 141 responders among
      the 172 patients analyzed. Full-thickness rotator cuff tears were higher in the
      ultrasound-guided subacromial subdeltoid injection group when compared with the
      glenohumeral joint injection group (P = 0.038) and abnormal bicipital tendon
      findings higher in the glenohumeral joint injection group (P = 0.016). There were
      no significant differences in specific abnormal U findings between responders
      versus nonresponders. Twelve patients had a shoulder magnetic resonance imaging
      and four patients underwent operative interventions after the injection.
      CONCLUSIONS: Overall pain reduction after ultrasound-guided shoulder injections
      was favorable in the short term. There was no specific preinjection point-of-care
      ultrasound findings associated with clinical pain reduction after injection.
      Additional imaging and operative intervention after ultrasound-guided shoulder
      injections seemed to be relatively low.

PMID- 28763327
TI  - Advanced Age is Not a Contraindication for Treatment With Curative Intent in
      Esophageal Cancer.
AB  - OBJECTIVES: The objective of this study is to compare long-term outcomes between
      younger and older (70 y and above) esophageal cancer patients treated with
      curative intent. MATERIALS AND METHODS: Overall survival (OS), disease-free
      survival (DFS), and locoregional recurrence-free interval were compared between
      older (70 y and above) and younger (below 70 y) esophageal cancer patients
      treated between 1998 and 2013. Treatment consisted of neoadjuvant
      chemoradiotherapy with surgery or definitive chemoradiotherapy: 36 to 50.4 Gy in
      18 to 28 fractions combined with 5-fluorouracil/cisplatin or
      carboplatin/paclitaxel. RESULTS: The study comprised 253 patients, of whom 76
      were 70 years and older. Median age was 64 years (range, 41 to 83). Most patients
      had stage II-IIIA disease (83%). Planned treatment was neoadjuvant
      chemoradiotherapy with surgery for 169 patients (41 patients aged 70 y and older)
      and definitive chemoradiotherapy for 84 patients (31 patients aged 70 y and
      older). The compliance to radiotherapy was 92%, with no difference between older
      and younger patients. In 33 patients (13 patients aged 70 y and older) planned
      surgery was not performed. Median follow-up was 4.9 years. Three-year OS was 42%.
      The multivariable analysis showed no statistical difference in OS or in DFS
      comparing older and younger patients: OS (hazard ratio [HR], 0.88; 95% confidence
      interval [CI], 0.61-1.28), DFS (HR, 0.87; 95% CI, 0.60-1.25). Elderly showed a
      longer locoregional recurrence-free interval; HR, 0.53 (95% CI, 0.30-0.92;
      P=0.02) and a higher pathologic complete response rate (50% vs. 25%; P=0.02).
      CONCLUSIONS: Long-term outcomes of older esophageal cancer patients (70 y and
      above) selected for treatment with neoadjuvant chemoradiotherapy followed by
      surgery or definitive chemoradiotherapy were comparable with the outcomes of
      their younger counterparts. Advanced age alone should not be a contraindication
      for potentially curative chemoradiotherapy-based treatment in esophageal cancer
      patients.

PMID- 28763328
TI  - Surgical Intervention in Gastric Carcinoid is Associated With Improved Survival
      in Local and Regional Disease.
AB  - INTRODUCTION: Gastric carcinoid is a rare entity with complex management options.
      This study aims to determine if surgical intervention in patients with local,
      regional, and metastatic gastric carcinoid is associated with prolonged survival.
      MATERIALS AND METHODS: The California Cancer Registry merged with the California
      Office of Statewide Health Planning and Development was queried for patients with
      a diagnosis of gastric carcinoid (2000 to 2011). Clinicopathologic
      characteristics, management, and outcomes were evaluated. RESULTS: There were
      1012 patients with a diagnosis of gastric carcinoid identified. The median age
      was 63 (range, 18 to 99) and the majority of patients were women (615, 60.7%).
      Most patients had localized disease (644, 64%), whereas 9.4% (95) had regional
      and 13.4% (133) had distant metastases at diagnosis. The majority of patients
      underwent gastric surgery (56.7%, n=574 vs. 43.2%, n=438). Prolonged survival was
      associated with gastric surgery in patients with both local (median survival not
      reached; P<0.0001) and regional disease (27 mo with surgery vs. 5 mo with no
      surgery; P=0.0007). In patients who underwent gastrectomy and resection of
      hepatic metastasis, the survival approached those patients who had surgery for
      only regional disease (26 vs. 27 mo, P=0.8721). CONCLUSIONS: Although the biology
      of the disease is the most significant predictor of overall outcome, when
      technically feasible and where comorbidities allow, aggressive endoscopic or
      surgical intervention should be offered for local and locoregional diseases,
      respectively.

PMID- 28763329
TI  - Efficacy of Modified Dose-dense Paclitaxel in Recurrent Cervical Cancer.
AB  - OBJECTIVE: To examine survival outcomes of women with recurrent cervical cancer
      who received salvage chemotherapy with modified dose-dense paclitaxel (MDDP)
      monotherapy (paclitaxel 80 mg/m, administered on day 1, 8, and 15 without day
      22). MATERIALS AND METHODS: A retrospective study was conducted to evaluate cause
      specific survival after the first recurrence (SAR) of women with recurrent
      cervical cancer diagnosed between 2006 and 2014. Pooled analyses were performed
      to examine SAR in women who received MDDP monotherapy (n=17) for any treatment
      line, compared with those who received salvage chemotherapy with paclitaxel
      doublet (n=18) and nonpaclitaxel regimens (n=52). RESULTS: In the whole cohort,
      median SAR was 13.7 months including 63 (72.4%) events. MDDP monotherapy regimen
      was most commonly used in the second-line setting (35.3%) followed by the
      third/fourth lines (both, 23.5%). Among the women who received MDDP regimen,
      there were 6 (35.3%) women who received >=6 cycles; there was 1 (5.9%) women who
      discontinued the regimen due to adverse effects (grade 3 transaminitis); regimen
      postponement was seen in 2 (1.4%) of 140 total cycles; and the response rate
      after the sixth cycle of this regimen was 29.4% (1 complete and 4 partial
      responses). On univariate analysis, MDDP usage had the highest 2-year SAR rate
      (MDDP 54.1%, paclitaxel-doublet 43.6%, and nonpaclitaxel regimens 28.1%;
      Ptrend=0.044). On multivariate analysis, MDDP monotherapy remained an independent
      prognostic factor for improved SAR compared with the nonpaclitaxel regimen
      (adjusted-hazard ratio, 0.50; 95% confidence interval, 0.26-0.95; P=0.036).
      CONCLUSION: Our results suggested that MDDP monotherapy is a tolerable and
      relatively effective regimen for recurrent cervical cancer.

PMID- 28763330
TI  - A Phase I Clinical Trial of the Phosphatidylserine-targeting Antibody Bavituximab
      in Combination With Radiation Therapy and Capecitabine in the Preoperative
      Treatment of Rectal Adenocarcinoma.
AB  - OBJECTIVES: There is interest in improving the tumoricidal effects of
      preoperative radiotherapy for rectal carcinoma by studying new radiosensitizers.
      The safety and toxicity profile of these combination regimens needs rigorous
      clinical evaluation. The primary objective of this study was to evaluate the
      toxicity of combining bavituximab, an antibody that targets exposed
      phosphatidylserine, with capecitabine and radiation therapy. MATERIALS AND
      METHODS: Patients with stage II or III rectal adenocarcinoma were enrolled on a
      phase I study combining radiation therapy, capecitabine, and bavituximab. A
      standard 3+3 trial designed was used. RESULTS: In general, bavituximab was safe
      and well tolerated in combination with radiation therapy and capecitabine in the
      treatment of rectal adenocarcinoma. One patient at the highest dose level
      experienced a grade III infusion reaction related to the bavituximab. One tumor
      demonstrated a complete pathologic response to the combination treatment.
      CONCLUSIONS: Bavituximab is safe in combination with capecitabine and radiation
      therapy at the doses selected for the study. Further clinical investigation would
      be necessary to better define the efficacy of this combination.

PMID- 28763331
TI  - Correlation between the trajectory of systolic blood pressure and new renal
      damage in a nonhypertensive population.
AB  - OBJECTIVE: This study aims to investigate the correlation between the trajectory
      of systolic blood pressure (SBP) and new renal damage in a nonhypertensive
      population. PATIENTS AND METHODS: This prospective cohort study included a total
      of 14 382 nonhypertensive individuals, employees of Kailuan Group of Companies,
      who took part in five healthy examinations in 2006-2007, 2008-2009, 2010-2011,
      2012-2013, and 2014-2015, and had complete data. These individuals were divided
      into four groups according to the different trajectories of SBP: low-low, low
      stable, middle-high, and high-high groups. The correlation between the trajectory
      of SBP and new renal damage in a nonhypertensive population was analyzed using a
      multivariate Cox's proportional hazard regression model. RESULTS: (a) A total of
      14 382 individuals had complete data and the average age of these individuals was
      44.6+/-10.8 years. Among these, 10 888 (75.7%) individuals were men and 3494
      (24.3%) individuals were women. (b) These individuals were divided into four
      groups according to different trajectories of blood pressure: low-low group,
      accounting for 13.15% (blood pressure was <106 mmHg); low-stable group,
      accounting for 53.91% (blood pressure was between 115 and 116 mmHg); middle-high
      group, accounting for 28.77% (blood pressure was between 125 and 131 mmHg); and
      high-high group, accounting for 4.6% (blood pressure was between 126 and 151
      mmHg). (c) With the increase in the trajectory of SBP, the detection rate of
      renal damage increased gradually. From the low-low group to the high-high group,
      the detection rates of estimated glomerular filtration rate (eGFR) less than 60
      ml/min/1.73 m were 2.3, 2.4, 3.6, and 4.3%, respectively; the positive rates of
      urinary protein were 1.7, 2.9, 3.8, and 5.5%, respectively; and the detection
      rates of eGFR less than 60 ml/min/1.73 m or positive urinary protein were 4, 5.2,
      7.3, and 9.3%, respectively (P<0.05). (d) After adjustment for other confounding
      factors, multivariate Cox's proportional hazard regression analysis showed that
      compared with the low-low group, the risk of eGFR less than 60 ml/min/1.73 m
      increased by nearly 1.5 times in the high-high group and in the low-stable,
      middle-high, and high-high groups, the risks of positive urinary protein, eGFR
      less than 60 ml/min/1.73 m, or positive urinary protein increased by 1.48-2.34
      and 1.20-1.70 times, respectively. CONCLUSION: In a nonhypertensive population,
      the high trajectory of SBP is a risk factor for kidney damage.

PMID- 28763332
TI  - Simultaneous validation of the SunTech CT40 automated blood pressure measurement
      device by the 1993 British Hypertension Society protocol and the Association for
      the Advancement of Medical Instrumentation/International Organization for
      Standardization 81060-2: 2013 standard.
AB  - OBJECTIVE: This study aimed to perform a simultaneous, third-party, independent
      validation of the oscillometric SunTech CT40 device for blood pressure (BP)
      measurement, according to the 1993 protocol of the British Hypertension Society
      and the standard of the Association for the Advancement of Medical
      Instrumentation (AAMI)/the International Organization for Standardization (ISO)
      81060-2:2013. PARTICIPANTS AND METHODS: Patient recruitment, study procedures,
      and data analysis followed the recommendations stated by the protocols. The study
      was approved by the institutional review board. RESULTS: A total of 94
      participants were included, 52 (55.3%) women, mean+/-SD age: 63.1+/-18.0 years,
      mean+/-SD arm circumference: 35.0+/-9.0 cm. The average of observers' entry BPs
      was 146.9+/-37.2 mmHg for systolic blood pressure (SBP) and 82.2+/-22.1 mmHg for
      diastolic blood pressure (DBP). Differences between the standard measurement and
      the test device within 5, 10, and 15 mmHg, for the better observer, were 79.4,
      96.5, and 100.0% for SBP and 82.6, 97.5, and 100.0% for DBP, respectively. The
      mean+/-SD differences between the readings obtained using the test device and
      those obtained by the observers (AAMI/ISO 81060-2:2013 standard criterion 1) were
      0.3+/-5.0 mmHg (SBP) and -0.8+/-4.3 mmHg (DBP), and the mean+/-SD differences
      between average of reference readings and average of test device readings in each
      patient (criterion 2) were 0.3+/-3.9 and -0.8+/-3.5 mmHg for SBP and DBP,
      respectively. CONCLUSION: The CT40 BP device achieved A/A grade of the British
      Hypertension Society protocol and fulfilled the requirements (criteria 1 and 2)
      of the AAMI/ISO standard. CT40 can be recommended for BP measurement in adults.

PMID- 28763333
TI  - Recent clinical trials in idiopathic inflammatory myopathies.
AB  - PURPOSE OF REVIEW: Idiopathic inflammatory myopathies (IIMs) are complex
      multisystemic autoimmune diseases. Glucocorticoids remain the cornerstone of
      treatment in IIM, and the benefit of additional immunosuppressors is still
      debated. A limited number of controlled clinical trials have been available to
      support treatment guidelines, but in the last year, several clinical trials have
      been published. In this review, the highlights of recently published and on-going
      clinical trials in IIM will be summarized and discussed. RECENT FINDINGS: Post
      hoc analyses of a large randomized controlled trial (RCT) suggested new
      predictive factors of response to rituximab in refractory IIM individuals. An
      international collaboration enabled the completion of a large RCT in early
      juvenile dermatomyositis that will orient first-line treatment in that
      population. New approaches are showing encouraging results in inclusion body
      myositis. SUMMARY: Recent advances in molecular mechanisms underlying IIM
      pathogenesis and the development of novel targeted therapies have influenced
      recent and on-going clinical research.

PMID- 28763334
TI  - Pseudomelanomas Following Stevens-Johnson Syndrome.
AB  - In this report, we present a novel case of pseudomelanoma, similar to that seen
      in a recurrent/traumatized nevus, in pre-existing nevi in a 36-year-old man a few
      months after recovering from an episode of severe Stevens-Johnson syndrome. The
      mechanism responsible for the atypical transformation of these nevi is likely the
      release of cytokines and growth factors in the microenvironment during the
      repair/regeneration process. It is important to be aware of this phenomenon, and
      specific inquiry about potential recent blistering skin disorder in addition to
      the other causes of trauma should be made when dealing with cases of
      pseudomelanoma to avoid misdiagnosis.

PMID- 28763335
TI  - Validation of Digital Pathology for Primary Histopathological Diagnosis of
      Routine, Inflammatory Dermatopathology Cases.
AB  - BACKGROUND: Digital pathology (DP) systems have been validated for routine,
      histopathological diagnosis by several investigators. The diagnostic matter in
      previous studies is composed mostly of neoplasms. However, in dermatopathology,
      inflammatory diseases constitute a greater proportion of cases and have been
      under-represented in this literature. Herein, we report the results of a
      prospective, DP side-by-side validation study comparing the histologic assessment
      of routine, clinical inflammatory dermatopathology cases by whole slide imaging
      (WSI) and traditional light microscopy (LM). METHODS: Glass slides were digitized
      at *40 magnification. Two dermatopathologists rendered diagnoses digitally and
      immediately thereafter by light microscopy. Additional recuts, special, and
      immunohistochemical stains obtained during workup were scanned and evaluated
      similarly. Morphological features used to make diagnoses and appreciable
      differences in histology were recorded. RESULTS: A total of 332 slides
      representing 93 cases were examined, including 157 hematoxylin & eosin sections,
      132 special stains, and 43 immunohistochemical slides. In total, 333 microscopic
      features important for rendering inflammatory diagnoses were identified. Two
      discrepant instances were noted wherein Gram-positive cocci were identified using
      traditional microscopy but not by DP (*40 scan). Eosinophils, melanin granules,
      and mucin were identified on both modalities but were noted to have different
      appearances. CONCLUSIONS: Our findings indicate that DP is sufficient for primary
      diagnosis in inflammatory dermatopathology. Higher magnification scanning may be
      required to identify submicron features, such as microorganisms. Subtle
      differences in image quality between these 2 modalities may contribute to varied
      histologic interpretations of which pathologists should be aware when validating
      clinical DP systems.

PMID- 28763336
TI  - Metastatic Cutaneous Paraganglioma: A Case Report and Review of the Literature.
AB  - Paragangliomas are rare neoplasms that arise from chromaffin cells of the
      sympathetic and parasympathetic nervous system. These tumors are often cured by
      surgical resection but the risk for metastatic disease exists, particularly for
      extra-adrenal paragangliomas. The behavior of these tumors is unpredictable, and
      clinical and histopathological features associated with malignancy have not been
      determined. The most common sites of metastases include local and distant lymph
      nodes, bone, liver, and lung. Cutaneous metastases are exceedingly rare with only
      2 reported cases, both of which presented on the scalp. Here we describe a 78
      year-old woman with cutaneous metastatic paraganglioma presenting as a forehead
      nodule, which developed 15 years after her initial diagnosis of paraganglioma.

PMID- 28763337
TI  - Folliculotropic Metastatic Melanoma: A Case Report and Review of the Literature.
AB  - Folliculotropic metastasis of cutaneous melanoma is rare, with only 5 published
      case reports in the English language literature since it was first described in
      2009. We report a 41-year-old man with a primary cutaneous melanoma of the right
      upper preauricular region with metastatic spread to the parotid gland and
      pulmonary lymph nodes. Excision of the primary lesion was performed and
      immunotherapy was initiated. Sixteen months later, the patient presented with 2
      new lesions of the left forehead and left neck. Histopathological examination was
      consistent with folliculotropic dermal deposits of metastatic melanoma. Deeper
      sectioning into the blocks revealed only sparse perifollicular pigment deposition
      and rare dermal melanocytes-a potential diagnostic pitfall had this been seen in
      the initial sections. This case represents the sixth and youngest patient to date
      with folliculotropic metastatic melanoma. This entity often presents in patients
      with advanced disease, including increased Breslow thickness and/or multiple
      metastases to lymph nodes, internal organs, or both. The folliculotropic
      metastases tend to be small and are often multiple. The precise relationship
      between folliculotropic primary melanoma and folliculotropic metastasis is
      unclear. In one reported case and in our patient, the primary tumor was noted to
      have a "folliculocentric" pattern. Because of the latter finding, the
      differential diagnosis includes multiple primary folliculotropic melanomas. Thus,
      clinical correlation and knowledge concerning the evolution of disease in the
      patient are critical. This case highlights a rare and unusual pattern of
      metastatic melanoma and potential problems in differential diagnosis.

PMID- 28763338
TI  - Bullous Erythema Nodosum Leprosum as the First Manifestation of Multibacillary
      Leprosy: A Rare Phenomenon.
AB  - Erythema nodosum leprosum (ENL) may uncommonly present before treatment in
      patients with multibacillary leprosy. Atypical manifestations are known in ENL
      and may be clinically misleading. Such wide variations in the clinical
      presentation of leprosy in reaction make histopathology an important tool for
      supporting clinical diagnosis. We report bullous ENL presenting as the first
      manifestation of leprosy in a 30-year-old Indian man diagnosed using
      histopathology.

PMID- 28763339
TI  - Long-term outcomes of transjugular intrahepatic portosystemic shunt in Indian
      patients with Budd-Chiari syndrome.
AB  - BACKGROUND/AIM: Transjugular intrahepatic portosystemic shunt (TIPS) is the
      treatment of choice in Budd-Chiari syndrome (BCS) based on current data. Our
      objective was to evaluate outcomes and assess prognostic factors in BCS patients
      undergoing TIPS. PATIENTS AND METHODS: In this retrospective analysis of a
      propectively maintained database, all consecutive BCS patients undergoing TIPS
      from September 2010 to February 2017 were included. Complete response after TIPS
      was defined as resolution of symptoms (ascites/pedal edema) with no requirement
      of diuretics at the end of 4 weeks. The Cox proportional hazard regression model
      was used to assess predictors of outcome and complications. RESULTS: Eighty
      patients with BCS who underwent TIPS were included; 40 (50%) were male. The mean
      age at onset of symptoms was 24.2+/-8.7 years. The median (range) follow-up was
      660 (2-2400) days. The 1-, 3-, and 5-year rates for TIPS stent patency were 89,
      81, and 81%, respectively. Cumulative encephalopathy-free rates were 91, 86, and
      86%, respectively, and survival rates were 93, 89, and 84%, respectively. Eight
      (10.0%) patients died during follow-up, five within the first year (three of
      these five had incomplete response). On univariate analysis, serum bilirubin,
      response to intervention, serum creatinine, Child class, model for end-stage
      liver disease, and All India Institute of Medical Sciences-hepatic venous outflow
      tract obstruction score were significantly different between survivors and
      nonsurvivors. On multivariate analysis, response to therapy after TIPS (hazard
      ratio: 8.37; 95% confidence interval: 1.60-43.82) was independently associated
      with mortality. The 1-year survival was 97% in patients with complete response,
      compared with 59% in those with incomplete response (P<0.004). CONCLUSION:
      Incomplete symptom response after TIPS is associated with poor outcome and can be
      used for selection of patients for liver transplantation.

PMID- 28763340
TI  - Rifaximin for the prevention of spontaneous bacterial peritonitis and hepatorenal
      syndrome in cirrhosis: a systematic review and meta-analysis.
AB  - Prophylactic antibiotics have been recommended in patients with a previous
      history of spontaneous bacterial peritonitis (SBP). Recently, there has been
      interest in the use of rifaximin for the prevention of SBP and hepatorenal
      syndrome (HRS). We conducted a meta-analysis to evaluate this association of
      rifaximin. We searched several databases from inception through 24 January 2017,
      to identify comparative studies evaluating the effect of rifaximin on the
      occurrence of SBP and HRS. We performed predetermined subgroup analyses based on
      the type of control group, design of the study, and type of prophylaxis. Pooled
      odds ratios (ORs) were calculated using a random effects model. We included 13
      studies with 1703 patients in the meta-analysis of SBP prevention. Pooled OR [95%
      confidence interval (CI)] was 0.40 (95% CI: 0.22-0.73) (I=58%). On sensitivity
      analysis, adjusted OR was 0.29 (95% CI: 0.20-0.44) (I=0%). The results of the
      subgroup analysis based on type of control was as follows: in the quinolone
      group, pooled OR was 0.42 (95% CI: 0.14-1.25) (I=55%), and in the no antibiotic
      group, pooled OR was 0.40 (95% CI: 0.18-0.86) (I=64%). However, with sensitivity
      analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (95% CI:
      0.17-0.63) (I=0%) and 0.28 (95% CI: 0.17-0.45) (I=0%) for the comparison with
      quinolones and no antibiotics, respectively. Pooled OR based on randomized
      controlled trials was 0.41 (95% CI: 0.22-0.75) (I=13%). For the prevention of
      HRS, the pooled OR was 0.25 (95% CI: 0.13-0.50) (I=0%). Rifaximin has a
      protective effect against the development of SBP in cirrhosis. However, the
      quality of the evidence as per the GRADE framework was very low. Rifaximin
      appeared effective for the prevention of HRS.

PMID- 28763341
TI  - Monitoring platelet reactivity during prasugrel or ticagrelor washout before
      urgent coronary artery bypass grafting.
AB  - OBJECTIVES: Patients with acute myocardial infarction pretreated with prasugrel
      or ticagrelor may require urgent coronary artery bypass grafting (CABG). However,
      prasugrel and ticagrelor withdrawal period is recommended for 5-7 days before
      planned CABG to enable full platelet recovery. We hypothesized that monitoring
      sequential platelet reactivity (PR) could identify patients with early platelet
      recovery who may benefit from earlier surgery before the guideline-recommended 5
      7 day delay. PATIENTS AND METHODS: We performed preoperative PR assays in 35
      patients with acute myocardial infarction who received prasugrel (60%) or
      ticagrelor (40%) and required an urgent CABG. When platelet inhibition levels
      were favorable, on the basis of the VerifyNow assay, surgery was endorsed. CABG
      related bleeding parameters were collected and compared with two matched control
      groups composed of patients who received fewer potent antiplatelet regimens.
      RESULTS: On the basis of platelet function monitoring, we identified 21 (56.7%)
      patients with a relatively earlier platelet recovery who underwent CABG before
      the end of the conventional washout period (5-7 days). For these patients, the
      washout periods were shortened to an average time of 2.6+/-1.0 days for
      ticagrelor and 3.8+/-1.5 days for prasugrel. CABG-related bleeding parameters
      were comparable with the two matched control groups. CONCLUSION: A strategy of
      performing preoperative PR assays can identify patients who recover platelet
      function in less than 5-7 days after ticagrelor or prasugrel discontinuation.
      This strategy may provide the basis for performing urgent CABGs earlier than the
      currently recommended delay. Future, larger studies are required to establish
      these preliminary findings.

PMID- 28763342
TI  - Apparent resistant hypertension and the risk of vascular events and mortality in
      patients with manifest vascular disease.
AB  - OBJECTIVE: Patients with apparent resistant hypertension (aRH) are at increased
      risk for developing cardiovascular disease. It is unknown if this condition is
      related to increased cardiovascular risk in patients with clinically manifest
      vascular disease. METHODS: In 6191 hypertensive patients with clinically manifest
      vascular disease, we evaluated the risk of subsequent vascular events and
      mortality between patients with controlled hypertension, uncontrolled
      hypertension, controlled aRH, and uncontrolled aRH. Controlled aRH was defined as
      office blood pressure less than 140/90 mmHg while using at least four
      antihypertensive drugs. Uncontrolled aRH was defined as office blood pressure at
      least 140/90 mmHg while using three antihypertensive drugs including a diuretic,
      or at least four antihypertensive drugs. Outcomes of interest were myocardial
      infarction, stroke, cardiovascular mortality, the composite outcome of
      cardiovascular events, and all-cause mortality. RESULTS: In total 2564 patients
      (41%) had controlled hypertension, 3063 patients (49%) had uncontrolled
      hypertension, 123 patients (2%) had controlled aRH, and 411 patients (7%) had
      uncontrolled aRH. During 7.1 years of follow-up patients with controlled aRH were
      at a higher risk of cardiovascular mortality [hazard ratios 1.86; 95% confidence
      interval (CI) 1.10-3.15], and all-cause mortality (hazard ratios 1.64; 95% CI
      1.07-2.52) compared with patients with controlled hypertension. Patients with
      uncontrolled aRH were at a higher risk of cardiovascular mortality (hazard ratios
      1.36; 95% CI 1.01-1.83), and higher risk of all-cause mortality (hazard ratios
      1.27; 95% CI 1.01-1.60) compared with patients with controlled hypertension.
      CONCLUSION: In hypertensive patients with clinically manifest vascular disease,
      presence of controlled and uncontrolled aRH is related to an increased risk of
      cardiovascular mortality and all-cause mortality.

PMID- 28763343
TI  - Home blood pressure normalcy in non-European adolescents.
AB  - OBJECTIVE: Evidence on normal range of home blood pressure (BP) in adolescents
      relies on only one European study. This study aims to investigate the normal
      range of home BP in a healthy non-European population of adolescents. METHODS:
      Cross-sectional study with a representative sample of secondary school students
      (12-17 years) from a Brazilian state capital. Adolescents' heights were
      classified in percentiles according to age and sex. Height percentiles were
      divided in 50th or less or more than 50th percentile. The home BP protocol
      included two day-time and two evening-time measurements over 6 days. Exams were
      considered valid with at least 12 measurements. RESULTS: A total of 1024
      adolescents were included, mean age 15.21 +/- 1.61 years, mostly women (52.4%),
      from public schools (68.4%) and nonwhite (51.3%). The 50th (midpoint of
      distribution) and the 95th percentile (upper normal limit) for home SBP and DBP
      in adolescents are provided by sex, age and height percentiles. There was a
      marked increase in the estimated 95th percentile for home SBP with increasing age
      in men for both height percentiles examined (16 mmHg for <=50th percentile and
      14.5 mmHg for >50th percentile) and less so for home DBP (1 and 5 mmHg,
      respectively). In women, the 95th percentile increase with age was less
      significant for SBP and similar for DBP when compared with men in the two height
      percentiles evaluated (6/2 mmHg for <=50th percentile and 4/4 mmHg for >50th
      percentile). CONCLUSION: Reference values for home BP by height percentiles for
      age and sex in a non-European population of adolescents are provided.

PMID- 28763344
TI  - The impact of fatigue and energy on work functioning and impairment in patients
      with major depressive disorder treated with desvenlafaxine.
AB  - Fatigue and low energy are cardinal symptoms of major depressive disorder (MDD)
      that have an impact on work functioning. Antidepressants with noradrenergic
      activity have been hypothesized to improve symptoms of fatigue and low energy. We
      examined the impact of these symptoms on work functioning in patients with MDD
      treated with the serotonin and noradrenaline reuptake inhibitor, desvenlafaxine.
      A secondary analysis was carried out from a study of employed adult outpatients
      (n=35) with MDD and subjective cognitive complaints treated with desvenlafaxine
      50-100 mg/day for 8 weeks. Multiple regression analyses modeled improvement in
      work functioning measures (Lam Employment Absence and Productivity Scale, Health
      and Work Performance Questionnaire, Sheehan Disability Scale) with measures of
      fatigue (Patient-Reported Outcomes Measurement Information System Fatigue scale
      and 20-item Hopkins Symptom Check List Energy scale). Patients showed a
      significant improvement in Montgomery-Asberg Depression Rating Scale scores as
      well as in fatigue and work functioning measures following treatment. Fatigue
      measures were significantly associated with improvement in some (Lam Employment
      Absence and Productivity Scale, Sheehan Disability Scale), but not all (Health
      and Work Performance Questionnaire) work functioning measures, independent of
      improvement in overall depressive symptoms. The limitations of this study include
      the small sample size and the lack of a placebo or a comparison group. Fatigue
      and low energy are important symptoms that are associated with occupational
      impairment in MDD. Treatments that improve these symptoms are likely to improve
      work functioning.

PMID- 28763345
TI  - Risk of hair loss with different antidepressants: a comparative retrospective
      cohort study.
AB  - The aim of this study was to quantify the risk of hair loss with different
      antidepressants. A retrospective cohort study design using a large health claims
      database in the USA from 2006 to 2014 was utilized. A cohort of new user and
      mutually exclusive users of fluoxetine, fluvoxamine, sertraline, citalopram,
      escitalopram, paroxetine, duloxetine, venlafaxine, desvenlafaxine, and bupropion
      were followed to the first diagnosis of alopecia. The cohort was comprised of 1
      025 140 new users of fluoxetine, fluvoxamine, sertraline, citalopram,
      escitalopram, paroxetine, duloxetine, venlafaxine, desvenlafaxine, and bupropion,
      with sertraline the most commonly prescribed (N=190 227) and fluvoxamine (N=3010)
      the least prescribed. Compared with bupropion, all other antidepressants had a
      lower risk of hair loss, with fluoxetine and paroxetine having the lowest risk
      [hazard ratio (HR)=0.68, 95% confidence interval (CI): 0.63-0.74, HR=0.68, 95%
      CI: 0.62-0.74, respectively] and fluvoxamine having the highest risk (HR=0.93,
      95% CI: 0.64-1.37). Compared with fluoxetine, bupropion had the highest risk of
      hair loss (HR=1.46, 95% CI: 1.35-1.58, number needed to harm=242 for 2 years) and
      paroxetine had the lowest risk (HR=0.99, 95% CI: 0.90-1.09). The results of this
      large population-based cohort study suggest an increase in the risk of hair loss
      with bupropion compared with selective serotonin reuptake inhibitors and
      selective norepinephrine reuptake inhibitors, whereas paroxetine had the lowest
      risk.

PMID- 28763346
TI  - The Authors Respond.

PMID- 28763347
TI  - Ex Vivo Induction of Multiple Myeloma-specific Immune Responses by Monocyte
      derived Dendritic Cells Following Stimulation by Whole-tumor Antigen of
      Autologous Myeloma Cells.
AB  - The introduction of novel agents has significantly expanded treatment options for
      multiple myeloma (MM), albeit long-term disease control cannot be achieved in the
      majority of patients. Vaccination with MM antigen-loaded dendritic cells (DCs)
      represents an alternative strategy that is currently being explored. The aim of
      this study was to assess the immunogenic potential of ex vivo-generated monocyte
      derived DCs (moDCs), following stimulation with the whole-antigen array of
      autologous myeloma cells (AMC). MoDCs were loaded with antigens of myeloma cells
      by 2 different methods: phagocytosis of apoptotic bodies from gamma-irradiated
      AMC, or transfection with AMC total RNA by square-wave electroporation. Twenty
      patients with MM were enrolled in the study. Following stimulation and
      maturation, moDCs were tested for their capacity to induce T-helper 1 and
      cytotoxic T lymphocyte responses in vitro. Both strategies were effective in the
      induction of myeloma-specific cytotoxic T lymphocyte and T-helper 1 cells, as
      demonstrated by cytotoxicity and ELISpot assays. On the whole, T-cell responses
      were observed in 18 cases by either method of DC pulsing. We conclude that both
      whole-tumor antigen approaches are efficient in priming autologous antimyeloma T
      cell responses and warrant further study aiming at the development of
      individualized DC vaccines for MM patients.

PMID- 28763349
TI  - Late respiratory effects of cancer treatment.
AB  - PURPOSE OF REVIEW: The aim of this article is to examine significant advances in
      our understanding of the late respiratory effects of cancer treatment, including
      surgery, radiotherapy, chemotherapy, biological therapies and haematopoietic stem
      cell transplant, and to provide a framework for assessing such patients. RECENT
      FINDINGS: Oncology therapies have advanced considerably over recent years but
      pulmonary toxicity remains a concern. Advances have been made in our
      understanding of the risk factors, including genetic ones that lead to toxicity
      from radiotherapy and chemotherapy and risk stratification models are being
      developed to aid treatment planning. Targeted biological treatments are
      continuously being developed and consequently the Pneumotox database of pulmonary
      toxicity continues to be an essential resource. Early detection of bronchiolitis
      obliterans in haematopoietic stem cell transplant patients has been found to be
      critical, with some positive results from intervention trials. SUMMARY: Pulmonary
      toxicity is a common unwanted consequence of life enhancing or saving cancer
      treatments which remain difficult to treat. Developments in these fields are
      mainly in the areas of prevention, early detection and monitoring of unwanted
      side effects. We discuss some of these developments within this review.

PMID- 28763350
TI  - A Prospective Randomized Study of Endoscopic Versus Conventional Harvesting of
      the Radial Artery.
AB  - OBJECTIVE: The aims of the study were to determine whether endoscopic harvesting
      of the radial artery (RA) reduces morbidity due to pain, infection, and
      disability with improvement in satisfaction and cosmesis compared to the
      conventional technique and (2) to compare the 6-month angiographic patency of the
      RA harvested conventionally and endoscopically. METHODS: In a prospective
      randomized study, 119 patients undergoing coronary artery bypass grafting using
      the RA were randomized to have RA harvested either conventionally (n = 59) or
      endoscopically (n = 60). RESULTS: Radial artery harvest time (open wound time)
      was significantly reduced in the endoscopic group (36.5 +/- 9.4 vs 57.7 +/- 9.4
      minutes, P < 0.001). Only one patient developed wound infection (1.6%) in the
      endoscopic group compared with six patients (10.2%), P = 0.061, in the
      conventional group. Although this was not statistically significant, clinically
      this was relevant in terms of reduction in postoperative morbidity. Postoperative
      pain in the arm incision was significantly lower in the endoscopic group at
      postoperative day 2 (P < 0.001) and at discharge (P < 0.001) and similar to the
      conventional open group at 6 weeks' follow-up (P = 0.103). Overall patient
      satisfaction and cosmesis were significantly better in the endoscopic group at
      postoperative day 2 (P < 0.001), at discharge (P < 0.001), and at 6 weeks' follow
      up (P < 0.001). There was no difference in the arm disability postoperatively (P
      = 0.505) between the two groups. Six-month angiographic assessment of 23 patients
      (12 endoscopic and 11 open) revealed no difference in the patency rate (10/12 in
      endoscopic and 9/11 in open group). CONCLUSIONS: Endoscopic RA harvesting reduced
      the incidence of postoperative wound infection and wound pain and improved
      patient satisfaction and cosmesis compared with conventional harvesting
      technique. There was no difference in the 6-month angiographic patency of the RA
      harvested conventionally and endoscopically.

PMID- 28763352
TI  - Vitamin D in Orthopaedics.

PMID- 28763351
TI  - Microlobectomy: A Novel Form of Endoscopic Lobectomy.
AB  - OBJECTIVE: Microlobectomy is a novel form of videoscopic-assisted thoracic
      surgery lobectomy. Strict inclusion criteria consist of the following: no
      intercostal incisions greater than 5 mm, 12 mm subxiphoid port, subxiphoid
      removal of the specimen, total endoscopic technique with CO2 insufflation, vision
      through a 5-mm camera, stapling via the subxiphoid port, or with 5-mm stapling
      devices. METHODS: The combined early experiences of six hospitals from three
      countries were combined from September 2014 to May 2016. During that time, the
      study represents a consecutive cohort study of this technique. RESULTS: Seventy
      two patients underwent microlobectomy. The median (range) age was 66 (27-82).
      Half of the patients were female. There were 48 right-sided resections and 24 on
      the left. There were four segmental resections and there was one right
      pneumonectomy. Four operations were performed robotically (with 8-mm intercostal
      incisions). The median (range) operative time was 180 (94-285) minutes and the
      blood loss was 118 (5-800) mL. There were three conversions to thoracotomy and
      two conversions to videoscopic-assisted thoracic surgery by means of an
      intercostal utility incision to complete the operation. The median (range) length
      of stay was 3 (1-44) days and 30 patients (42%) when home by day 2 and 16
      patients (22%) were discharged on day 1. There were no deaths. Five patients (7%)
      had a prolonged airleak. There were no wound infections and there was one
      incisional hernia. CONCLUSIONS: We believe that microlobectomy is an interesting
      novel form of videoscopic-assisted thoracic surgery lobectomy and has several
      theoretical advantages. We have presented our early results and hope that this
      will stimulate others to investigate this type of videoscopic-assisted thoracic
      surgery lobectomy further.

PMID- 28763353
TI  - Team Approach: Combined Orthopaedic and Vascular Injury.

PMID- 28763354
TI  - Stemless Shoulder Arthroplasty: Review of Early Clinical and Radiographic
      Results.

PMID- 28763355
TI  - Regulatory Considerations for Physiological Closed-Loop Controlled Medical
      Devices Used for Automated Critical Care: Food and Drug Administration Workshop
      Discussion Topics.
AB  - Part of the mission of the Center for Devices and Radiological Health (CDRH) at
      the US Food and Drug Administration is to facilitate medical device innovation.
      Therefore, CDRH plays an important role in helping its stakeholders such as
      manufacturers, health care professionals, patients, patient advocates, academia,
      and other government agencies navigate the regulatory landscape for medical
      devices. This is particularly important for innovative physiological closed-loop
      controlled (PCLC) devices used in critical care environments, such as intensive
      care units, emergency settings, and battlefield environments. CDRH's current
      working definition of a PCLC medical device is a medical device that incorporates
      physiological sensor(s) for automatic manipulation of a physiological variable
      through actuation of therapy that is conventionally made by a clinician. These
      emerging devices enable automatic therapy delivery and may have the potential to
      revolutionize the standard of care by ensuring adequate and timely therapy
      delivery with improved performance in high workload and high-stress environments.
      For emergency response and military applications, automatic PCLC devices may play
      an important role in reducing cognitive overload, minimizing human error, and
      enhancing medical care during surge scenarios (ie, events that exceed the
      capability of the normal medical infrastructure). CDRH held an open public
      workshop on October 13 and 14, 2015 with the aim of fostering an open discussion
      on design, implementation, and evaluation considerations associated with PCLC
      devices used in critical care environments. CDRH is currently developing
      regulatory recommendations and guidelines that will facilitate innovation for
      PCLC devices. This article highlights the contents of the white paper that was
      central to the workshop and focuses on the ensuing discussions regarding the
      engineering, clinical, and human factors considerations.

PMID- 28763356
TI  - Randomized Controlled Trial of the Clinical Efficacy of Multiport Versus Uniport
      Wire-Reinforced Flexible Catheters for Labor Epidural Analgesia.
AB  - BACKGROUND: The purpose of this prospective, randomized, controlled trial was to
      determine whether multiple ports improve the analgesic efficacy of wire
      reinforced flexible catheters used for labor epidural analgesia (LEA). METHODS:
      Six hundred fifty laboring patients were randomized to receive epidural analgesia
      using either a multiport or uniport wire-reinforced flexible catheter. The
      primary outcome was analgesic success, defined as the incidence of adequate
      analgesia following the initial bolus given to initiate LEA. Secondary outcomes
      included the number of patients requiring clinician interventions during
      maintenance of LEA; anesthetic success, defined as the incidence of adequate
      anesthesia following the initial bolus given to establish surgical anesthesia for
      cesarean delivery; and maternal satisfaction with the overall quality of LEA.
      RESULTS: There was no significant difference in analgesic success at initiation
      of LEA between the uniport and the multiport wire-reinforced flexible catheter
      (93.6% vs 89.5%, respectively; difference of 4.1% [95% confidence interval, -0.4%
      to 8.5%]; P = .077). There was also no difference in the number of patients
      requiring clinician interventions during maintenance of LEA and in anesthetic
      success at the establishment of surgical anesthesia for cesarean delivery between
      the 2 catheter types. CONCLUSIONS: Multiple ports do not appear to improve the
      analgesic efficacy of wire-reinforced flexible catheters used for LEA.

PMID- 28763357
TI  - Variability in the Use of Protective Mechanical Ventilation During General
      Anesthesia.
AB  - BACKGROUND: The purpose of this study was to determine whether significant
      variation exists in the use of protective ventilation across individual
      anesthesia providers and whether this difference can be explained by patient,
      procedure, and provider-related characteristics. METHODS: The cohort consisted of
      262 anesthesia providers treating 57,372 patients at a tertiary care hospital
      between 2007 and 2014. Protective ventilation was defined as a median positive
      end-expiratory pressure of 5 cm H2O or more, tidal volume of <10 mL/kg of
      predicted body weight and plateau pressure of <30 cm H2O. Analysis was performed
      using mixed-effects logistic regression models with propensity scores to adjust
      for covariates. The definition of protective ventilation was modified in
      sensitivity analyses. RESULTS: In unadjusted analysis, the mean probability of
      administering protective ventilation was 53.8% (2.5th percentile of provider
      19.9%, 97.5th percentile 80.8%). After adjustment for a large number of
      covariates, there was little change in the results with a mean probability of
      51.1% (2.5th percentile 24.7%, 97.5th percentile 77.2%). The variations persisted
      when the thresholds for protective ventilation were changed. CONCLUSIONS: There
      was significant variability across individual anesthesia providers in the use of
      intraoperative protective mechanical ventilation. Our data suggest that this
      variability is highly driven by individual preference, rather than patient,
      procedure, or provider-related characteristics.

PMID- 28763358
TI  - Effects of Esmolol on the Esophagogastric Junction: A Double-Blind, Randomized,
      Crossover Study on 14 Healthy Volunteers.
AB  - BACKGROUND: Passive regurgitation may occur throughout the perioperative period,
      increasing the risk for pulmonary aspiration and postoperative pulmonary
      complications. Hypnotics and opioids, especially remifentanil, that are used
      during anesthesia have been shown to decrease the pressure in the esophagogastric
      junction (EGJ), that otherwise acts as a barrier against passive regurgitation of
      gastric contents. Esmolol, usually used to counteract tachycardia and
      hypertension, has been shown to possess properties useful during general
      anesthesia. Like remifentanil, the beta-1-adrenoreceptor antagonist may be used
      to attenuate the stress reaction to tracheal intubation and to modify
      perioperative anesthetic requirements. It may also reduce the need for opioids in
      the postoperative period. Its action on the EGJ is however unknown.The aim of
      this trial was to compare the effects of esmolol and remifentanil on EGJ
      pressures in healthy volunteers, when administrated as single drugs. METHODS:
      Measurements of EGJ pressures were made in 14 healthy volunteers using high
      resolution solid-state manometry. Interventions were administered in a randomized
      sequence and consisted of esmolol that was given IV as a bolus dose of 1 mg/kg
      followed by an infusion of 10 MUg.kg.minute over 15 minutes, and remifentanil
      with target-controlled infusion of 4 ng/mL over 15 minutes. Interventions were
      separated by a 20-minute washout period. Analyses of EGJ pressures were performed
      at baseline, and during drug administration at 2 (T2) and 15 minutes (T15). The
      primary outcome was the inspiratory EGJ augmentation, while the inspiratory and
      expiratory EGJ pressures were secondary outcomes. RESULTS: There was no effect on
      inspiratory EGJ augmentation when comparing remifentanil and esmolol (mean
      difference -4.0 mm Hg [-9.7 to 1.7]; P= .15). In contrast, remifentanil
      significantly decreased both inspiratory and expiratory pressures compared to
      esmolol (-12.2 [-18.6 to -5.7]; P= .003 and -8.0 [-13.3 to -2.8]; P= .006).
      CONCLUSIONS: Esmolol, compared with remifentanil, does not affect EGJ function.
      This may be an advantage regarding passive regurgitation and esmolol may thus
      have a role to play in anesthesia where maintenance of EGJ barrier function is of
      outmost importance.

PMID- 28763359
TI  - More Than a Tick Box: Medical Checklist Development, Design, and Use.
AB  - Despite improving patient safety in some perioperative settings, some checklists
      are not living up to their potential and complaints of "checklist fatigue" and
      outright rejection of checklists are growing. Problems reported often concern
      human factors: poor design, inadequate introduction and training, duplication
      with other safety checks, poor integration with existing workflow, and cultural
      barriers. Each medical setting-such as an operating room or a critical care unit
      and different clinical needs-such as a shift handover or critical event response
      require a different checklist design. One size will not fit all, and checklists
      must be built around the structure of medical teams and the flow of their work in
      those settings. Useful guidance can be found in the literature; however, to date,
      no integrated and comprehensive framework exists to guide development and design
      of checklists to be effective and harmonious with the flow of medical and
      perioperative tasks. We propose such a framework organized around the 5 stages of
      the checklist life cycle: (1) conception, (2) determination of content and
      design, (3) testing and validation, (4) induction, training, and implementation,
      and (5) ongoing evaluation, revision, and possible retirement. We also illustrate
      one way in which the design of checklists can better match user needs in specific
      perioperative settings (in this case, the operating room during critical events).
      Medical checklists will only live up to their potential to improve the quality of
      patient care if their development is improved and their designs are tailored to
      the specific needs of the users and the environments in which they are used.

PMID- 28763361
TI  - Dexmedetomidine-Associated Hyperthermia: A Series of 9 Cases and a Review of the
      Literature.
AB  - Dexmedetomidine, an alpha2-adrenergic agonist, can be used to perform mild to
      moderate sedation in critically ill patients. In this case series, 9
      cardiovascular intensive care unit patients with hyperthermia during
      dexmedetomidine administration, suggestive of drug fever, are presented.
      Hyperthermia (>38.5 degrees C) occurred 6 (4-10) hours (median [interquartile
      range]) after dexmedetomidine initiation at a dose of 1.0 (0.8-1.3) MUg/kg/h and
      was resolved 3 (1-8) hours after discontinuation of dexmedetomidine. All patients
      were screened for infectious and noninfectious causes of hyperthermia, and the
      findings were analyzed by 2 adverse drug reaction (ADR) assessment methods-the
      World Health Organization-Uppsala Monitoring Centre (WHO-UMC) Causality
      Assessment and the Naranjo ADR scale. This resulted in a "probable" ADR in all 9
      patients (WHO) and a "probable" and "possible" ADR in 1 and 8 patients (Naranjo),
      respectively. This case series supports published case reports, suggesting that
      dexmedetomidine administration may be associated with the occurrence of
      clinically relevant hyperthermia. The underlying mechanisms and risk factors are
      uncertain and require further research.

PMID- 28763362
TI  - Survival After Primary Debulking Surgery Compared With Neoadjuvant Chemotherapy
      in Advanced Ovarian Cancer: A National Cancer Database Study.
AB  - OBJECTIVE: The aim of this study was to compare overall survival (OS) of women
      with advanced ovarian cancer treated with primary debulking surgery (PDS) or
      neoadjuvant chemotherapy (NAC) using a large national cohort. METHODS: The 1998
      2011 National Cancer Database was queried to identify women with stage III or IV
      ovarian cancer treated with multiagent chemotherapy and stage-appropriate
      surgery. Overall survival was estimated and compared using Kaplan-Meier analysis
      between women who received PDS followed by multiagent chemotherapy or NAC
      followed by interval surgery. Multivariable Cox proportional hazards regression
      model tested for associations of potential explanatory variables with OS.
      Analyzed confounders included age, composite comorbidity scores, stage, grade,
      histology, insurance status, income quartile, and race. RESULTS: Overall, 44,907
      women (85.9%) underwent PDS, and 7348 women (14.1%) received NAC. Women who
      received NAC were older (64 vs 61 years, P < 0.001), had higher comorbidity
      scores (P < 0.001), and more often had stage IV disease (44.1% vs 26.1%, P <
      0.001). Median OS was 41.1 (40.5-41.7) months among women who underwent PDS
      compared with 30.3 (29.3-31.1) months among women who received NAC (log-rank, P <
      0.001). Among women with stage III disease, PDS was associated with increased OS
      compared with NAC (median OS, 44.9 [44.2-45.7] vs 31.4 [30.2-33.0] months; hazard
      ratio [95% confidence interval], 0.70 [0.66-0.76]; P < 0.001). Among women with
      stage IV disease, there was no OS difference between PDS and NAC cohorts (median
      OS, 31.2 [30.4-32.3] vs 28.4 [27.2-30.2] months; hazard ratio [95% confidence
      interval], 0.93 [0.85-1.02]; P = 0.12). CONCLUSIONS: Primary debulking surgery
      was associated with increased OS among women with stage III but not stage IV
      ovarian cancer in a nationally representative cohort with low NAC use. If this
      finding reflects treatment assignment bias, it suggests that providers often well
      select candidates for PDS rather than NAC, although median OS times remain low.

PMID- 28763363
TI  - Ovarian Cancer in Elderly Patients: Patterns of Care and Treatment Outcomes
      According to Age and Modified Frailty Index.
AB  - OBJECTIVE: The present study assessed the predictive value of age and Modified
      Frailty Index (mFI) on the management of primary epithelial ovarian cancer (EOC)
      patients aged 70 years or older (elderly). METHODS: A retrospective multicenter
      study selected elderly EOC patients treated between 2006 and 2014. Treatments
      were analyzed according to the following age group categories: (1) 70 to 75 years
      versus (2) older than 75 years, and mFI of less than 4 (low frailty) versus
      greater than or equal to 4 (high frailty). RESULTS: Seventy-eight patients were
      identified (40 in age group 1 and 38 in age group 2). The mFI was greater than or
      equal to 4 in 23 women. Median age of low frailty and high frailty was not
      significantly different (75.6 vs 75.3). Comorbidities were equally distributed
      according to age, whereas diabetes, hypertension, obesity, and chronic renal
      failure were more frequent in the high-frailty group. Performance status was
      different only according to mFI. Twenty percent of age group 1 versus 55.3% of
      age group 2 underwent none or only explorative surgical approach (P = 0.003),
      whereas surgical approaches were similar in the 2 frailty groups. The rate of
      postoperative complications was higher in high-frailty patients compared with low
      frailty patients (23.5% vs 4.3%; P = 0.03). Chemotherapy was administered to all
      the patients, a monotherapy regimen to 50% of them. No differences in toxicity
      were registered, except more hospital recovery in the high-frailty cohort. Median
      survival time was in favor of younger patients (98 versus 30 months) and less
      frailty patients (56 vs 27 months). CONCLUSIONS: Elderly EOC patients can receive
      an adequate treatment, but patients who are older than 75 years can be
      undertreated, if not adequately selected. The pretreatment assessment of frailty
      through mFI could be suggested in the surgical and medical management.

PMID- 28763364
TI  - Adjuvant Therapy Use and Survival in Stage II Endometrial Cancer.
AB  - OBJECTIVE: Radiotherapy (RT) is an established adjuvant treatment for stage II
      endometrioid endometrial carcinoma (EEC). The role of chemotherapy (CT) in stage
      II EEC is less proven. We used the National Cancer Data Base to identify factors
      associated with adjuvant CT in stage II EEC and to explore whether receipt of CT
      was associated with improved overall survival (OS). METHODS/MATERIALS: Women
      diagnosed in 2010 to 2013 with International Federation of Obstetrics and
      Gynecology stage II EEC (grades 1-3) after hysterectomy and bilateral salpingo
      oophorectomy were identified in the National Cancer Data Base. Multivariable
      logistic regression was used to identify covariates associated with receipt of
      CT. Overall survival among patients receiving RT, CT, or chemoradiotherapy (CRT)
      after surgery was compared using Kaplan-Meier estimates, the log-rank test, Cox
      proportional hazards regression, and propensity score matching. RESULTS: We
      identified 6102 stage II EEC patients. There were 358 patients (6%) who received
      adjuvant CT alone and 525 (9%) who received CRT; the remainder received RT alone
      (n = 1906; 31%) or no adjuvant treatment (n = 3313; 54%). The presence of
      lymphovascular invasion (odds ratio, 3.58; P < 0.001) and grade 3 disease (odds
      ratio, 3.40; P < 0.001) was strongly associated with receipt of CT or CRT. The OS
      at 3 years for the entire cohort was 89%. On multivariable analysis, CT versus RT
      was associated with worse OS (hazard ratio [HR], 2.12 [95% confidence interval,
      1.46-3.06]; P < 0.001), whereas CRT versus RT was not associated with improved OS
      (HR, 1.07 [95% confidence interval, 0.71-1.62]; P = 0.781). After propensity
      score matching, there remained no difference in OS between RT and CRT (HR, 1.14;
      P = 0.614). CONCLUSIONS: Patients with stage II EEC have an excellent prognosis,
      and most undergo observation or receive adjuvant RT in the United States. Receipt
      of CT (alone or with RT) was not associated with an OS advantage compared with RT
      alone in this observational cohort. Randomized trials will help clarify the role
      of CT in stage II patients.

PMID- 28763365
TI  - Ultrasound-Guided Laparoscopic Ovarian Wedge Resection in Recurrent Serous
      Borderline Ovarian Tumours.
AB  - OBJECTIVE: The aim of this study was to demonstrate the use of intraoperative
      ultrasound-guided ovarian wedge resection in the treatment of recurrent serous
      borderline ovarian tumors (sBOTs) that are too small to be visualized
      laparoscopically. METHODS: This was a prospective analysis of all women with
      recurrent sBOTs that were not visible laparoscopically, who underwent
      intraoperative ultrasound-guided ovarian wedge resection between January 2015 and
      December 2016 at the West London Gynaecological Cancer Centre, Imperial College
      NHS Trust, London, United Kingdom. RESULTS: We evaluated 7 patients, with a
      median age of 35 years (range, 28-39 years). Six women were nulliparous, whereas
      1 woman had a single child. Previous surgical intervention left 5 women with a
      single ovary, whereas the remaining 2 had previous ovarian-sparing surgery. The
      median size of recurrence was 18 mm (range, 12-37 mm). All women underwent
      uncomplicated intraoperative guided ovarian wedge resections. Histological
      assessment confirmed sBOT in all 7 cases. Six of the women remain disease-free.
      One woman recurred postoperatively with her third recurrence, who previously had
      bilateral disease and noninvasive implants with microinvasive disease and
      micropapillary pattern. No cases progressed to invasive disease. The median
      follow-up time was 12 months (range, 1-20 months). One pregnancy has been
      achieved postoperatively but resulted in miscarriage. CONCLUSIONS: Continuous
      intraoperative ultrasound can be used to facilitate complete tumor excision in
      recurrent sBOT while minimizing the removal of ovarian tissue in women with
      recurrent sBOT. It is essential that surgical techniques evolve simultaneously
      with diagnostic imaging modalities to enable surgeons to treat such pathology.

PMID- 28763366
TI  - Does BLOODCARE Powder Prevent Postoperative Chylous Ascites After Lymphadenectomy
      for Gynecological Malignancies?
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of an intraoperative
      hemostatic cellulose agent (BLOODCARE powder [Life Line, Brno, Czech Republic])
      on reducing the incidence of postoperative chylous ascites (PCA) after complete
      pelvic and para-aortic lymphadenectomy (PPALN) in patients with gynecological
      cancers treated with laparotomy. METHODS: This case control study reviewed 150
      patients with gynecological cancer who underwent PPALN. In the study group (n =
      75), BLOODCARE powder was applied below the left renal vein and bilateral
      obturator fossa. In the control group (n = 75), no sealant agent was used after
      the procedure, such as fibrin glue or a hemostatic cellulose agent. RESULTS: The
      demographic and surgical characteristics of the patients in both groups were
      similar. Chylous ascites occurred in 9 cases (6%). The incidence of PCA was lower
      in the study group (1 [1.3%] vs 8 [10.7%]; P = 0.03). Logistic regression
      analysis indicated that using BLOODCARE powder during the surgery independently
      protected against the development of PCA. CONCLUSIONS: Using BLOODCARE powder
      during retroperitoneal surgery may prevent PCA. This simple, effective agent
      should be used after PPALN for gynecological cancers.

PMID- 28763367
TI  - Preoperative Vaginal Metronidazole Decreases the Risk of Pelvic Infections After
      Radical Robotic Hysterectomy.
AB  - OBJECTIVES: Risk factors and infection rates of radical robotic procedures have
      yet to be described in gynecology. A practice improvement strategy using a
      solitary dose of vaginal metronidazole the night before surgery was initiated to
      determine if it decreased the risk of pelvic infection. METHODS: A retrospective
      chart review of robotic radical hysterectomies for gynecologic malignancy at our
      institution from April 2010 through April 2016 was performed. Demographic data,
      operative data, and data on use of metronidazole before surgery were collected.
      chi Statistical analysis, Student t test, and multivariate analysis were
      performed to analyze the data. RESULTS: Ninety-four patients met the inclusion
      criteria, and 46 patients received vaginal metronidazole. Demographic and
      clinical factors were similar between the 2 groups. The pelvic infection rate was
      significantly higher in nonusers at 13% (6/46) compared with users at 0% (0/42)
      (P <= 0.05). The genitourinary infection rate was also significantly higher in
      nonusers at 20% as compared with users at 2.2% (P = 0.02). Operative risk factors
      found to be associated with pelvic infection included hospital length of stay,
      blood loss, and metronidazole use. Multivariate regression analysis determined
      that only vaginal metronidazole had a clinically significant reduction of pelvic
      and genitourinary infection. DISCUSSION: A single dose of preoperative vaginal
      metronidazole reduces the risk of pelvic and genitourinary infection after
      robotic radical hysterectomy.

PMID- 28763368
TI  - Veliparib Monotherapy to Patients With BRCA Germ Line Mutation and Platinum
      Resistant or Partially Platinum-Sensitive Relapse of Epithelial Ovarian Cancer: A
      Phase I/II Study.
AB  - OBJECTIVE: A new treatment principle, which seems to radically change the
      treatment approach in ovarian cancer (OC), has developed over the past few years.
      Poly(ADP-ribose) polymerase inhibitors work by interfering with mechanisms
      important to DNA damage repair. Cancer cells that already have defects in the
      BRCA genes are particularly sensitive to treatment with poly(ADP-ribose)
      polymerase inhibitors. The main purpose of this study was to investigate the
      effect of veliparib in patients with known BRCA1/2 mutations and with a platinum
      resistant or intermediate sensitive relapse of OC. METHODS: Major eligibility
      criteria were primary epithelial ovarian/fallopian/peritoneal cancer patients
      with a platinum-resistant or intermediate sensitive relapse of OC and with
      evaluable disease by either Response Evaluation Criteria In Solid Tumors or
      Gynecological Cancer Intergroup CA-125 criteria. Patients were treated with oral
      veliparib twice daily on days 1 to 28. RESULTS: Sixteen patients were enrolled in
      the phase I part, and a maximum tolerable dose of 300 mg twice daily was
      established. The phase II part enrolled 32 patients with a median of 4 previous
      treatment regimens. The overall response rate combining Response Evaluation
      Criteria In Solid Tumors and CA-125 response was 65% (6% complete response and
      59% partial response). Progression-free and overall survival rates of the
      intention-to-treat population were 5.6 months (95% confidence interval, 5.2-7.3
      months) and 13.7 months (95% confidence interval, 10.2-17.3 months),
      respectively. The most common phase II treatment-related grade 2 toxicities
      included fatigue (22%), nausea (22%), and vomiting (9%). CONCLUSIONS: Treatment
      with veliparib in heavily pretreated patients with relapse of OC demonstrates a
      considerable efficacy with an acceptable toxicity profile.

PMID- 28763369
TI  - Sentinel Lymph Node Biopsy in the Management of Vulvar Carcinoma: An Evidence
      Based Insight.
AB  - OBJECTIVE: Lymph node metastasis has been shown to represent the most significant
      prognostic factor in vulvar carcinoma. Because only 25% to 35% of patients with
      early stage disease have lymph node metastases, a significant 65% to 75% possibly
      do not benefit from elective inguinofemoral lymphadenectomy considering the
      related morbidities of wound infection, breakdown, and lower limb lymphedema.
      This review article aims to present and summarize the evidence available with
      regard to sentinel lymph node (SLN)-guided management of vulvar carcinoma.
      MATERIALS AND METHODS: A literature search was performed in MEDLINE resources
      using the subject headings "vulvar neoplasms," "sentinel lymph node," "sentinel
      lymph node biopsy," and "lymphatic metastasis." This search returned 886 articles
      that were published through January 2017. Prospective studies investigating
      sentinel node identification techniques and their impact on vulvar cancer
      management and prognosis were considered. Case reports were excluded from the
      review. RESULTS: Technetium-99-m-labeled nanocolloid with or without blue dye and
      more recently indocyanine green fluorescence have been the main techniques used
      for SLN identification in vulvar carcinoma. Radioisotope and near-infrared
      techniques have been shown to be superior to blue dye particularly with midline
      lesions that drain bilaterally or that drain directly to a deep pelvic node.
      Patients with a small unifocal primary tumor (<4 cm) and no obvious preoperative
      metastasis have been shown to have low groin recurrence rates and excellent
      disease-specific survival rates with minimal treatment-related morbidity when
      undergoing SLN biopsy-guided management. CONCLUSIONS: Sentinel lymph node biopsy
      guided management seems to be safe when restricted to International Federation of
      Gynecology and Obstetrics IB to II cases where tumors are unifocal, less than 4
      cm in size, and when there is no evidence of lymph node metastasis on
      clinical/radiological assessment. This reduces operative morbidity in this cohort
      of patients.

PMID- 28763372
TI  - Xinxuekang Regulates Reverse Cholesterol Transport by Improving High-density
      Lipoprotein Synthesis, Maturation, and Catabolism.
AB  - Di'ao Xinxuekang (XXK) is an herbal product in China and the Netherlands that has
      been clinically shown to attenuate atherosclerosis; however, the underlying
      antiatherosclerotic mechanism remains unclear. Because of its role in cholesterol
      homeostasis, reverse cholesterol transport (RCT) is a potential target for these
      beneficial effects. This study investigated the effects of XXK on RCT and related
      proteins. After treating ApoE-deficient mice with XXK for 8 weeks, we observed an
      increase in the expression level of ATP-binding cassette transporter A1 and ATP
      binding cassette transporter G1, which in turn stimulated cholesterol efflux and
      reduced aortic atherosclerotic lesion area. XXK also increased high-density
      lipoprotein (HDL) synthesis by modulating the peroxisome proliferator-activated
      receptor gamma/liver X receptor alpha/ATP-binding cassette transporter A1 pathway
      and promoted HDL maturity by increasing serum lecithin-cholesterol
      acyltransferase. In addition, XXK improved the selective uptake of HDL
      cholesteryl ester by increasing the expression of scavenger receptor class B type
      I. This is the first study to show that XXK confers a regulation of RCT, at least
      in part, by improving HDL synthesis, maturation, and catabolism.

PMID- 28763373
TI  - Comparison of two radiological methods in the determination of skeletal maturity
      in the Indian pediatric population.
AB  - To determine a more precise and reliable method between Greulich-Pyle (GP) and
      MacKay's (MK) method for the determination of skeletal age in an Indian pediatric
      population. We carried out a cross sectional study for the assessment of skeletal
      age on the basis of examination of hand and wrist radiographs of 106 patients (1
      15 years of age) who presented with soft tissue injury to hand by the GP and the
      MK method. These radiographs were evaluated by a radiologist and an orthopedic
      surgeon independently. In girls, the mean age difference between chronological
      and skeletal age was 8 months by the GP method, whereas it was 17 months by MK
      method. For boys, the mean age difference was 10 months by the GP method and by
      MKs method, it was 20 months. By the GP method, 44% of the boys showed a more
      reliable estimate of age whereas it was 10% by the MK method. However, the same
      for girls was 25% by the GP method and 16% by the MK method. The inter-rater
      reliability for the raters was found to be kappa=0.68 and this was statistically
      significant (P<0.001), 95% confidence interval (0.504-0.848). We concluded that
      the GP method appeared to be more reliable in the determination of skeletal age
      in the Indian pediatric population.

PMID- 28763375
TI  - Integrating Measures of Social Determinants of Health Into Health Care
      Encounters: Opportunities and Challenges.

PMID- 28763376
TI  - Effects of task language and second-language proficiency on the neural correlates
      of phonemic fluency in native Japanese speakers: a functional near-infrared
      spectroscopy study.
AB  - Data collected during a phonemic fluency task (or 'FAS test'), a standard
      component of neuropsychological batteries for assessment of cognitive deficits,
      may be language-dependent and may differ depending on second-language
      proficiency. The unique orthographic/phonological system of the task language,
      and the reported cognitive advantages inherent to bilinguals, may each influence
      the task's neural correlates. However, language background is not currently
      assessed in most studies testing phonemic fluency. Here, we used 52-channel
      functional near-infrared spectroscopy in college-aged native-Japanese subjects to
      examine functional changes in oxygenated hemoglobin elicited during a phonemic
      fluency task performed in Japanese and in English. We found activity differences
      that were related to task language and second-language proficiency. Besides loci
      activated in the Japanese test, bilateral precentral channels were specifically
      recruited in the English test. Furthermore, the higher-proficiency group showed
      almost no increase in oxygenated hemoglobin in either language context, whereas
      participants with lower proficiency showed widespread increases for both
      contexts. We interpret precentral increases as the consequence of additional
      articulatory resource recruitment in a second-language context. As for the lack
      of such variation in the higher-proficiency group, it may reflect an advantage in
      nonverbal executive control in this group. Together, our results point to
      language background and proficiency as confounding variables in neuroimaging
      studies of phonemic fluency and that the adequacy of such measures in populations
      with varying language backgrounds needs to be considered in future studies.

PMID- 28763374
TI  - The Veterans Affairs Cardiac Risk Score: Recalibrating the Atherosclerotic
      Cardiovascular Disease Score for Applied Use.
AB  - BACKGROUND: Accurately estimating cardiovascular risk is fundamental to good
      decision-making in cardiovascular disease (CVD) prevention, but risk scores
      developed in one population often perform poorly in dissimilar populations. We
      sought to examine whether a large integrated health system can use their
      electronic health data to better predict individual patients' risk of developing
      CVD. METHODS: We created a cohort using all patients ages 45-80 who used
      Department of Veterans Affairs (VA) ambulatory care services in 2006 with no
      history of CVD, heart failure, or loop diuretics. Our outcome variable was new
      onset CVD in 2007-2011. We then developed a series of recalibrated scores,
      including a fully refit "VA Risk Score-CVD (VARS-CVD)." We tested the different
      scores using standard measures of prediction quality. RESULTS: For the 1,512,092
      patients in the study, the Atherosclerotic cardiovascular disease risk score had
      similar discrimination as the VARS-CVD (c-statistic of 0.66 in men and 0.73 in
      women), but the Atherosclerotic cardiovascular disease model had poor
      calibration, predicting 63% more events than observed. Calibration was excellent
      in the fully recalibrated VARS-CVD tool, but simpler techniques tested proved
      less reliable. CONCLUSIONS: We found that local electronic health record data can
      be used to estimate CVD better than an established risk score based on research
      populations. Recalibration improved estimates dramatically, and the type of
      recalibration was important. Such tools can also easily be integrated into health
      system's electronic health record and can be more readily updated.

PMID- 28763371
TI  - Proinflammatory Cytokines Mediate GPCR Dysfunction.
AB  - Proinflammatory reaction by the body occurs acutely in response to injury that is
      considered primarily beneficial. However, sustained proinflammatory cytokines
      observed with chronic pathologies such as metabolic syndrome, cancer, and
      arthritis are detrimental and in many cases is a major cardiovascular risk
      factor. Proinflammatory cytokines such as interleukin-1, interleukin-6, and tumor
      necrosis factor alpha (TNFalpha) have long been implicated in cardiovascular risk
      and considered to be a major underlying cause for heart failure (HF). The failure
      of the anti-TNFalpha therapy for HF indicates our elusive understanding on the
      dichotomous role of proinflammatory cytokines on acutely beneficial effects
      versus long-term deleterious effects. Despite these well-described observations,
      less is known about the mechanistic underpinnings of proinflammatory cytokines
      especially TNFalpha in pathogenesis of HF. Increasing evidence suggests the
      existence of an active cross-talk between the TNFalpha receptor signaling and G
      protein-coupled receptors such as beta-adrenergic receptor (betaAR). Given that
      betaARs are the key regulators of cardiac function, the review will discuss the
      current state of understanding on the role of proinflammatory cytokine TNFalpha
      in regulating betaAR function.

PMID- 28763377
TI  - Unfamiliar faces in recognition memory: spaced learning enhances subsequent
      recognition memory by reducing repetition priming.
AB  - Although the spacing effect is one of most robust effects in learning, its
      cognitive and neural mechanisms are still under investigation. Whether the
      spacing effect is achieved by reducing neural repetition priming or depends on
      learning experience is still unclear. In this event-related potential study,
      participants were asked to memorize 140 novel faces, half under the massed
      learning condition and the other half under the spaced learning condition. The
      afterwards recognition tests indicated that participants recognized more items
      under the spaced learning condition than under the massed learning condition. The
      electroencephalography data suggested that spaced learning was associated with a
      reduced familiarity effect in frontal N400. Remembered faces showed smaller
      repetition priming than forgotten faces under both learning conditions and spaced
      learning significantly reduced repetition suppression. Although no direct
      association was found between repetition priming and episodic memory, the
      difference in quantity between spaced learning and massed learning in the
      repetition priming can predict the different quantities in the recognition
      memory. These results suggest that the neural mechanism of the spacing effect is
      influenced by experience; however, the impact is mainly repetition priming and
      the spacing effect is still very robust.

PMID- 28763378
TI  - Facial emotion recognition deficits in children with and without attention
      deficit hyperactivity disorder: a behavioral and neurophysiological approach.
AB  - The current study examined the facial emotion recognition ability with a
      simultaneous assessment of behavioral and neurophysiological data in children
      with and without attention deficit hyperactivity disorder (ADHD) aged 7-17 years
      using a facial emotion matching task and event-related potential measurements
      (event-related potential components N170 and N250 at T5 and T6) in an emotional
      continuous performance task. Group differences and interaction effects of
      children's performance (both behavioral and neurophysiological) were evaluated
      between children with ADHD and children without ADHD as well as between younger
      and older children. No deficit in facial emotion recognition was found for
      children with ADHD compared with children without ADHD even with
      neurophysiological parameters. However, in terms of developmental differences,
      the younger children differentiated in their behavioral and neurophysiological
      performance from the older children. No interaction was detected between the
      experimental groups and the age groups, indicating that developmental progression
      in terms of emotional processes did not differ between children with and without
      ADHD. This study indicates that the facial emotion recognition is above all an
      age-dependent function with later processing of facial emotion expressions in
      younger compared with older children and suggests that a facial emotion
      recognition deficit is secondary in children with ADHD and might occur only with
      specific emotions or ADHD subtypes, but not in the whole ADHD population.

PMID- 28763379
TI  - Environmental Public Health Tracking: From Data to Action.

PMID- 28763380
TI  - Environmental Public Health Tracking Program Advances and Successes: Highlights
      From the First 15 Years.
AB  - Over the past 15 years, the National Environmental Public Health Tracking Program
      (Tracking Program) has advanced technologically and programmatically, evolving
      from an abstract concept to a mature program. The Tracking Program, in
      collaboration with national, state, and local partners, uses data and expertise
      to identify and address environmental public health needs and improve public
      health capacity across the United States. Examples of the successful application
      of environmental public health tracking include informing health impact
      assessments and filling data gaps. The Tracking Program plans to continue working
      to direct innovative programs and solutions that protect and improve community
      health in years to come. With support from the Tracking Program, health
      departments can enhance their abilities to plan and conduct environmental public
      health activities.

PMID- 28763381
TI  - CDC's National Environmental Public Health Tracking Program in Action: Case
      Studies From State and Local Health Departments.
AB  - The Centers for Disease Control and Prevention's (CDC's) National Environmental
      Public Health Tracking Program (Tracking Program) is a multidisciplinary
      collaboration that involves the ongoing collection, integration, analysis,
      interpretation, and dissemination of data from environmental hazard monitoring,
      human exposure surveillance, and health effects surveillance. With a renewed
      focus on data-driven decision-making, the CDC's Tracking Program emphasizes
      dissemination of actionable data to public health practitioners, policy makers,
      and communities. The CDC's National Environmental Public Health Tracking Network
      (Tracking Network), a Web-based system with components at the national, state,
      and local levels, houses environmental public health data used to inform public
      health actions (PHAs) to improve community health. This article serves as a
      detailed landscape on the Tracking Program and Tracking Network and the Tracking
      Program's leading performance measure, "public health actions." Tracking PHAs are
      qualitative statements addressing a local problem or situation, the role of the
      state or local Tracking Program, how the problem or situation was addressed, and
      the action taken. More than 400 PHAs have been reported by funded state and local
      health departments since the Tracking Program began collecting PHAs in 2005.
      Three case studies are provided to illustrate the use of the Tracking Program
      resources and data on the Tracking Network, and the diversity of actions taken.
      Through a collaborative network of experts, data, and tools, the Tracking Program
      and its Tracking Network are actively informing state and local PHAs. In a time
      of competing priorities and limited funding, PHAs can serve as a powerful tool to
      advance environmental public health practice.

PMID- 28763382
TI  - Economic Valuation of Selected Illnesses in Environmental Public Health Tracking.
AB  - BACKGROUND: In benefit-cost analysis of public health programs, health outcomes
      need to be assigned monetary values so that different health endpoints can be
      compared and improvement in health can be compared with cost of the program.
      There are 2 major approaches for estimating economic value of illnesses:
      willingness to pay (WTP) and cost of illness (COI). In this study, we compared
      these 2 approaches and summarized valuation estimates for 3 health endpoints
      included in the Centers for Disease Control and Prevention's National
      Environmental Public Health Tracking Network-asthma, carbon monoxide (CO)
      poisoning, and lead poisoning. METHOD: First, we compared results of WTP and COI
      estimates reported in the peer-reviewed literature when these 2 methods were
      applied to the same study participants. Second, we reviewed the availability and
      summarized valuations using these 2 approaches for 3 health endpoints. RESULT:
      For the same study participants, WTP estimates in the literature were higher than
      COI estimates for minor and moderate cases. For more severe cases, with
      substantial portion of the costs paid by the third party, COI could exceed WTP.
      Annual medical cost of asthma based on COI approach ranged from $800 to $3300 and
      indirect costs ranged from $90 to $1700. WTP to have no asthma symptoms ranged
      from $580 to $4200 annually. We found no studies estimating WTP to avoid CO or
      lead poisoning. Cost of a CO poisoning hospitalization ranged from $14 000 to $17
      000. For patients who sustained long-term cognitive sequela, lifetime earnings
      and quality-of-life losses can significantly exceed hospitalization costs. For
      lead poisoning, most studies focused on lead exposure and cognitive ability, and
      its impact on lifetime earnings. CONCLUSION: For asthma, more WTP studies are
      needed, particularly studies designed for conditions that involve third-party
      payers. For CO poisoning and lead poisoning, WTP studies need to be conducted so
      that more comprehensive economic valuation estimates can be provided. When COI
      estimates are used alone, it should be clearly stated that COI does not fully
      capture the nonmarket cost of illness, such as pain and suffering, which
      highlights the need for WTP estimates.

PMID- 28763383
TI  - Addressing Data Inequities in American Indian Communities Through an
      Environmental Public Health Tracking Pilot Project.
AB  - National and state surveillance systems identify American Indians/Alaska Natives
      inconsistently and often inaccurately within their data sets. Consequently,
      communities may not be represented with data at the level of geography needed.
      Collecting and presenting environmental and health-related data to the public are
      done by state Tracking Networks. Great Lakes Inter-Tribal Epidemiology Center
      (GLITEC) conducted a groundbreaking 2014 Tribal Environmental Health Tracking
      pilot project that engaged tribes, an urban Indian community, 3 state health
      departments, a Tribal Epidemiology Center (TEC), and a federal agency. Two other
      TECs-the Albuquerque Area Southwest Tribal Epidemiology Center (AASTEC) and
      Northwest Tribal Epidemiology Center (NW EpiCenter)-are now modeling GLITEC's
      project. They will forge active partnerships with at least one tribe and build
      relationships with state Tracking programs, explore environmental priorities,
      identify health outcomes of greatest concern for each community, and determine
      whether environmental or health inquiries can be addressed through state Tracking
      data. The Tribal Environmental Health Tracking pilot project provides an example
      of how state public health Tracking programs can be responsive to data
      inequities, build relationships between tribes/urban Indian communities, and
      increase their competency for working with indigenous communities.

PMID- 28763384
TI  - Using Tracking Data to Promote Environmental Public Health Through Regulatory and
      Legislative Processes in New York City.
AB  - Legislation and regulation are powerful tools for decreasing health risks from
      environmental hazards. Legislation is enacted by an elected body, and regulations
      are issued by an agency in the executive branch delegated authority by the
      legislature to carry out enacted laws. The New York City (NYC) Environmental
      Public Health Tracking Program makes data and analytic findings available to
      policy makers to inform development of sound and effective environmental health
      legislation and regulation. Tracking data and associated science create awareness
      of environmental hazards and health impacts, guide strategies for mitigating
      hazards, and sustain support for effective law by documenting beneficial impacts
      on the environment and health. We describe how environmental and health
      surveillance data and analytic findings have informed legislation and regulations
      related to restaurant food safety and air pollution control in NYC. Using data to
      guide legislative and regulatory processes helps ensure that policy decisions and
      directions are based on objective evidence.

PMID- 28763385
TI  - A Spatial Analysis of Acute Myocardial Infarction Rates in New York State in
      Relation to Hospitals Along State Jurisdictional Borders.
AB  - INTRODUCTION: Patients experiencing acute myocardial infarction (AMI) are likely
      to visit the nearest hospital providing appropriate services since timely care is
      a critical determinant in the treatment and progression of AMI. We comparatively
      examined AMI rates in border and nonborder census tracts. The New York State
      (NYS) Environmental Public Health Tracking (EPHT) program, in conjunction with
      the Statewide Planning and Research Cooperative System, will work on developing
      memoranda of understanding with neighboring states to be able to more
      comprehensively access NYS residents' out-of-state health records. OBJECTIVE: To
      determine whether AMI rates in the NYS border census tracts differ from AMI rates
      in nonborder census tracts as a preliminary exploration of the utilization of out
      of-state care for acute health conditions by NYS border residents. DESIGN: We
      reviewed data on inpatient and emergency department visits in NYS with discharge
      dates from 2005 to 2014 retrospectively. We used the NYS EPHT tier 1 system
      database to locate hospitals. We geocoded all cases to NYS 2010 census tracts. We
      mapped differences between border and nonborder tracts and analyzed resulting
      spatial patterns. We computed tract-level AMI rates and differences between
      border and nonborder AMI rates. RESULTS: The age-adjusted AMI rates differed by
      8.2 cases per 10 000 people (95% confidence interval, 6.94-12.60). Maps showed
      patterns of differences in AMI rates, especially along the NYS border with New
      England and other geographically closer out-of-state hospitals. CONCLUSIONS: AMI
      rates that were geographically closer to out-of-state hospitals were lower,
      suggesting that people residing in border census tracts are utilizing out-of
      state care. Our study adds to literature on the geographical component of health
      care accessibility and utilization in the context of acute conditions such as AMI
      and lends impetus to access out-of-state health records to better understand
      health care facility access and utilization for NYS residents.

PMID- 28763386
TI  - Estimating the Public Health Impact of Air Pollution for Informing Policy in the
      Twin Cities: A Minnesota Tracking Collaboration.
AB  - OBJECTIVE: The Minnesota Department of Health and the Minnesota Pollution Control
      Agency used local air pollution and public health data to estimate the impacts of
      particulate matter and ozone on population health, to identify disparities, and
      to inform decisions that will improve health. SETTING: While air quality in
      Minnesota currently meets federal standards, urban communities are concerned
      about the impact of air pollution on their health. The Twin Cities (Minneapolis
      St Paul) metropolitan area includes 7 counties where fine particulate levels and
      rates of asthma exacerbations are elevated in some communities. DESIGN: We used
      the Environmental Protection Agency's BenMAP (Environmental Benefits Mapping and
      Analysis Program) software, along with local PM2.5 (fine particulate) and ozone
      ambient concentrations, census and population health data, to calculate impacts
      for 2008 at the zip code level. The impacts were summed across all zip codes for
      area-wide estimates. American Community Survey data were used to stratify zip
      codes by poverty and race for assessment of disparities. MAIN OUTCOME MEASURES:
      Attributable fraction, attributable rate and counts for all-cause mortality,
      asthma and chronic obstructive pulmonary disease hospitalizations, asthma
      emergency department (ED) visits, and cardiovascular disease hospitalizations.
      RESULTS: In the Twin Cities (2008), air pollution was a contributing cause for an
      estimated 2% to 5% of respiratory and cardiovascular hospitalizations and ED
      visits and between 6% and 13% of premature deaths. The elderly (aged 65+ years)
      experienced the highest air pollution-attributable rates of death and respiratory
      hospitalizations; children experienced the highest asthma ED visit rates.
      Geographical and demographic differences in air pollution-attributable health
      impacts across the region reflected the differences in the underlying morbidity
      and mortality rates. CONCLUSIONS: Method was effective in demonstrating that
      changes in air quality can have quantifiable health impacts across the Twin
      Cities. Key messages and implications from this work were shared with the media,
      community groups, legislators and the public. The results are being used to
      inform initiatives aimed at reducing sources of air pollution and to address
      health disparities in urban communities.

PMID- 28763387
TI  - The South Carolina Environmental Public Health Tracking Program's Role in
      Monitoring and Reducing Occupational Exposure to Lead: Public Health Actions in
      Collaboration with the South Carolina Occupational Safety and Health
      Administration.
AB  - Per South Carolina (SC) Law S44-29-10, all blood lead test records are
      reportable. The SC Environmental Public Health Tracking (SC EPHT) program is
      directly involved in blood lead surveillance in SC, as it maintains the blood
      lead record database. Although Adult Blood Lead Epidemiology and Surveillance
      funding from the Centers for Disease Control and Prevention was discontinued in
      2013, SC EPHT has continued to monitor and record adult blood lead test
      records.In 2012, SC EPHT signed a memorandum of understanding with the SC
      Occupational Safety and Health Administration (SC OSHA). Per this agreement,
      quarterly reports of elevated adult blood lead concentrations (>=25 MUg/dL) are
      supplied to SC OSHA, along with North American Industry Classification System
      codes of employers. This information is used for industrial inspections,
      mitigation, and abatement related to lead. The SC EPHT program's collaboration
      with SC OSHA has resulted in a number of public health actions that have improved
      the health and well-being of workers in SC. Of the 3 nationally accepted SC
      public health actions related to occupational lead exposure, 2 detail
      investigations and citations by SC OSHA. The other describes internal analyses
      conducted by the SC EPHT program regarding elevated blood lead levels in adults
      and associations with specific North American Industry Classification System
      codes.In this review, we outlined the role of SC EPHT related to adult blood lead
      surveillance in SC, including implementation of the memorandum of understanding
      with SC OSHA. We also examined demographics of adult blood lead records in SC for
      2010-2015 and summarized public health actions related to occupational lead
      exposure in SC. Since federal funding for the SC EPHT program was initiated in
      2009, the program has played an important part in lead surveillance in SC. The
      resulting health benefits to those with the potential for occupational exposure
      to lead are extremely important.

PMID- 28763388
TI  - Health Impact Assessments and Extreme Weather-Challenges for Environmental
      Health.
AB  - BACKGROUND: The Florida Department of Health, Environmental Public Health
      Tracking Program, in collaboration with the Escambia County Health Department and
      the University of West Florida, used the Health Impact Assessment Framework to
      examine adverse health outcomes that may be related to an extreme flood event in
      Pensacola, Florida (Escambia County) during April 29 to May 3, 2014. In this 2014
      flood event, portions of Pensacola received more than 15.5 in of rain in a single
      day. Infrastructure impacts from this extreme event included destroyed bridges
      and roads and the failure of many sewage lift stations. OBJECTIVE: To determine
      whether there were associated increases in injury, illness, and death, data on
      reportable diseases, hospitalizations, emergency department (ED) visits, and
      deaths that occurred during the impact period in 2014 were compared with a
      control period in 2008. DESIGN: We used an ecological design to compare impact
      and control periods and examined the proportion of hospitalizations, ED visits,
      and deaths potentially attributable to the extreme flood event. RESULTS: The
      results of this comparison were mixed, with some Escambia County zip codes
      showing increased hospitalizations and ED visits, and some zip codes showing a
      decrease. However, countywide, there were increases in the proportion of both
      injury- and respiratory-related hospitalizations and ED visits during the impact
      period. CONCLUSIONS: It is challenging to characterize human health impacts from
      natural disasters such as extreme floods. Still, it is believed that specific
      policy changes could result in fewer health impacts during future flood events.
      For example, this study recommended raising the electric panels on lift stations
      above the flood elevation to keep them operational during extreme rainfall
      events. For more maps and tables, consult the complete project report available
      online at
      http://www.floridatracking.com/HealthTrackFL/document/Escambia_HIA_Report.pdf.

PMID- 28763389
TI  - Improving Outreach and Surveillance Efforts Following a Large-Scale Carbon
      Monoxide Poisoning in Wisconsin.
AB  - OBJECTIVE: In December 2014, the largest carbon monoxide (CO) poisoning in
      Wisconsin's history occurred at an ice arena. Following this event, the Wisconsin
      Environmental Public Health Tracking (WI EPHT) Program sought to improve outreach
      and surveillance efforts. METHODS: WI EPHT designed and distributed educational
      materials on CO poisoning prevention and surveyed stakeholders to gauge the
      effectiveness of outreach efforts. To enhance surveillance, WI EPHT utilized data
      from the Wisconsin Poison Center (WPC) to generate real-time alerts of anomalous
      numbers of CO-related calls. RESULTS: WI EPHT found that 42% of stakeholders
      reviewed the outreach materials, and 1 ice arena had installed a CO detector as a
      result. CO alerts were developed using WPC data and are now routinely used in
      statewide public health surveillance. CONCLUSION: WI EPHT staff improved CO
      poisoning prevention outreach and saw a positive response among stakeholders.
      This work demonstrates ways that health agencies can improve outreach and
      surveillance for CO poisoning. Improvements in these areas can bolster public
      health response and may prevent CO-related illness and injury.

PMID- 28763390
TI  - Taking Action With Data: Improving Environmental Public Health at the Community
      Level.
AB  - CONTEXT: The Wisconsin Environmental Public Health Tracking Program (Wisconsin
      Tracking) compiles and provides data on health endpoints and related
      environmental exposures as a resource to local health departments, tribes,
      academia, and other stakeholders. The goal of providing these data is that
      stakeholders use them to develop projects that improve environmental health in
      their communities-that is, moving from "data to action." OBJECTIVE: To encourage
      use of Wisconsin Tracking data, we developed a minigrants program and issued a
      funding opportunity to local health departments and tribes. The opportunity
      requested proposals for small projects using our data, with the goal of making
      public health improvements in those communities. Wisconsin Tracking evaluated the
      minigrants program after its completion. DESIGN/SETTING: Eight local health
      departments in Wisconsin were awarded up to $10 500 to develop and implement
      projects over a 9-month period. METHODS: Wisconsin Tracking created a funding
      opportunity announcement requiring utilization of our data to develop projects by
      local health departments in Wisconsin. We reviewed and scored applications,
      evaluating proposals on a range of criteria. During the 9-month project period,
      Wisconsin Tracking staff members provided a variety of technical assistance to
      grantees. An evaluation of the overall program followed. RESULTS: Funded
      communities used Wisconsin Tracking data to improve public health infrastructure,
      leverage partnerships, establish new initiatives, respond to emergencies, improve
      communication with stakeholders and residents, and make a variety of public
      health improvements in their communities. CONCLUSIONS: Efforts to increase use of
      our data catalyzed development of small-scale environmental health projects. This
      minigrants program was successful at building relationships between local health
      departments and Wisconsin Tracking, increasing awareness of Wisconsin Tracking
      data and resources, and contributing to numerous documented public health
      improvements throughout Wisconsin.

PMID- 28763391
TI  - Spatial Surveillance of Childhood Lead Exposure in a Targeted Screening State: An
      Application of Generalized Additive Models in Denver, Colorado.
AB  - CONTEXT: The targeted nature of Colorado's childhood lead screening program
      presents several analytical issues that complicate routine epidemiologic
      surveillance. OBJECTIVES: To analyze spatial patterns of childhood lead exposure
      among children younger than 6 years, identifying areas of increased risk along
      with associated covariates. METHODS: We analyzed a spatial case-control data set
      of childhood lead poisoning using generalized additive models. Incident cases
      were represented by the residential locations of children younger than 6 years
      with confirmed elevated blood lead levels (EBLL) of 5 MUg/dL or more recorded
      between calendar years 2010 and 2014, and controls were sampled from the
      population at risk. We modeled the effect of spatial location, adjusting for
      potential spatial confounders. We also adjusted for a number of covariates
      previously identified in the childhood lead poisoning literature to understand
      the ecologic-level drivers of spatial variation in risk. MAIN OUTCOME MEASURE(S):
      Crude and adjusted spatial odds ratios describing the relative frequency of lead
      poisoning among different locations in Denver, Colorado. RESULTS: We found
      evidence of statistically significant spatial clustering in incident cases of
      lead poisoning even after adjustment for age, sex, year, season, and spatially
      smoothed screening rate. Spatial confounder-adjusted odds ratios in the Denver
      study area ranged from 0.22 to 2.7. Adjusting for additional ecologic-level
      covariates effectively accounted for the observed spatial variation. We found
      that ecologic-level indicators of low socioeconomic status, Hispanic ethnicity,
      Asian race, and older housing age were all positively and significantly
      associated with an increased EBLL risk. CONCLUSION: Housing and socioeconomic
      factors continue to be the primary ecologic risk factors associated with
      childhood lead exposure and can be used to predict risk at a fine spatial
      resolution in the Denver study area. Our analysis demonstrates how other targeted
      screening states can be proactive about childhood lead surveillance within their
      major population centers and enhance the spatial specificity of lead mitigation
      efforts.

PMID- 28763392
TI  - Four Corners States Biomonitoring Consortium: Lessons Learned During
      Implementation.
AB  - Building on a history of collaboration in environmental public health and
      biomonitoring activities, laboratory and environmental epidemiology leaders in
      Arizona, Colorado, New Mexico, and Utah created the Four Corners States
      Biomonitoring Consortium, which is now in its third year of activities. In this
      article, we briefly highlight some lessons learned during the implementation
      phases of the consortium, including the processes of collaborating to identify
      common environmental exposure concerns, prioritizing those concerns, identifying
      cohorts and communities with potential risks of excessive exposure, developing a
      model for conducting exposure investigations, and the challenges presented during
      the implementation phases and early fieldwork activities. Detailed information on
      these topics can be found at www.4csbc.org. The advantages of collaborating with,
      and leveraging the resources of, state Environmental Public Health Tracking
      Networks and Public Health Emergency Preparedness programs are discussed. Using
      one example from the early stages of this work, we also discuss the potential of
      biomonitoring as a vehicle for empowering the public to make informed choices to
      control their exposures and to influence public health decisions, support science
      based environmental health policy and program development, and respond to
      emerging environmental exposure concerns.

PMID- 28763393
TI  - Environmental Health Tracking Improves Pesticide Use Data to Enable Research and
      Inform Public Health Actions in California.
AB  - Pesticides have adverse impacts on the environment and public health. In response
      to growing public concern over these impacts, California implemented the
      Pesticide Use Reporting (PUR) program in 1990. The PUR program is widely
      recognized as the world's most comprehensive pesticide reporting system, and its
      pesticide application records are highly detailed. However, the complexity and
      volume of PUR data require a level of data skills and resources beyond many
      government agencies, public health professionals, and community stakeholders.
      Over the past decade, the California Environmental Health Tracking Program has
      undertaken multiple strategies to make PUR data more accessible, understandable,
      and useful to a diversity of data users. Three specific efforts are described in
      detail-the Pesticide Linkage Service, the Pesticide Mapping Tool, and a policy
      relevant analysis on pesticide use near schools-as are their impacts on
      environmental and public health research, community outreach and education, and
      policy change.

PMID- 28763395
TI  - The time has come for a safe, effective way to relieve menopausal symptoms.

PMID- 28763394
TI  - Changing the conversation about hormone therapy.

PMID- 28763396
TI  - Is outpatient hysteroscopy accurate for the diagnosis of endometrial pathology
      among perimenopausal and postmenopausal women?
AB  - OBJECTIVE: To assess the histological and visual accuracy of outpatient
      hysteroscopy. METHODS: This was a retrospective analysis of all women referred to
      a tertiary center outpatient hysteroscopy clinic between March 2011 and October
      2016 for the following indications: postmenopausal bleeding, suspected polyp,
      and/or thick endometrium. Histological accuracy was evaluated by comparing
      specimens obtained in hysteroscopy with those obtained by hysterectomy, and
      visual accuracy was evaluated by comparing visual findings with those obtained by
      biopsies. Sensitivity, specificity, positive predictive value, negative
      predictive value, and likelihood ratio were calculated to assess visual accuracy.
      RESULTS: The mean age of participants was 54.14 (interquartile range 43.0-64.0).
      A total of 408 pathological specimens were obtained from outpatient
      hysteroscopies during the 712 visits recorded in the clinic log. Histological
      accuracy was evaluated in 15 participants who eventually underwent hysterectomy.
      Total percent of agreement between hysteroscopy biopsies and final pathology
      obtained by hysterectomy was 73% (kappa = 0.47). Overall visual accuracy was
      calculated with a 93.1% sensitivity, 52.1% specificity, 90.4% positive predictive
      value, and 61.0% negative predictive value. Visual accuracy for benign pathology
      was generally higher compared with that for pre and malignant lesions. Visual
      accuracy was satisfactory for the diagnosis of endometrial carcinoma with
      sensitivity and specificity of 71.4% and 98.9%, respectively, but poor for
      diagnosing hyperplasia with sensitivity and specificity of 25.0% and 96.6%,
      respectively. CONCLUSIONS: Outpatient hysteroscopy is an adequate and reliable
      tool for the evaluation of benign pathology in the uterine cavity. Visual
      findings may not suffice, and directed biopsies may be required to improve
      diagnostic accuracy.

PMID- 28763397
TI  - Application of the 21-item Vulvovaginal Symptoms Questionnaire in postmenopausal
      Spanish women.
AB  - OBJECTIVE: To assess vulvovaginal symptoms and urinary incontinence in
      postmenopausal women. Secondarily to evaluate factors related to the severity of
      vulvovaginal symptoms and the internal consistency of the used tools. METHODS: In
      this cross-sectional study, the Spanish language version of the 21-item
      Vulvovaginal Symptoms Questionnaire (VSQ) and the 3-item International
      Consultation on Incontinence Questionnaire (ICIQ-SF) were applied to 122
      postmenopausal Spanish women aged 45 to 75 years. RESULTS: Mean age of the whole
      sample was 59.5 +/- 4.9 years; 89.3% had natural menopause, 77.9% reported
      vulvovaginal symptoms, 54.9% had urinary incontinence, 54.1% were sexually
      active, and 77.0% currently had a partner. Calculated Cronbach's alpha
      coefficients were 0.87 and 0.88 for the VSQ and the ICIQ-SF, respectively.
      Multiple linear regression analysis determined that total VSQ scores (more severe
      vulvovaginal symptoms) were positively correlated with female age, parity,
      surgical menopause, being sexually active, economic problems, phytoestrogen use,
      and more severe urinary incontinence. An inverse correlation was found with urban
      residency and time since menopause onset. CONCLUSIONS: Internal consistency of
      the VSQ and the ICIQ-SF was good in this postmenopausal sample in which age,
      sexual activity, urinary incontinence, drug use, and other personal aspects were
      important covariates determining the severity of vulvovaginal symptoms.

PMID- 28763398
TI  - Cardiovascular fat in women at midlife: effects of race, overall adiposity, and
      central adiposity. The SWAN Cardiovascular Fat Study.
AB  - OBJECTIVES: Cardiovascular fat (CF) is associated with greater coronary heart
      disease (CHD) risk. Postmenopausal women have greater CF volumes than
      premenopausal women, and the association between specific CF depot volumes and
      CHD risk is more pronounced after menopause. Race, central adiposity, and
      visceral adiposity are important factors that could impact CF volumes. Whether
      racial differences in CF volumes and in their associations with central (visceral
      fat [VAT]) and general adiposity (body mass index [BMI]) exist in midlife women
      have not been addressed before. METHODS: In all, 524 participants from the Study
      of Women's Health Across the Nation (mean age: 50.9 +/- 2.9 years; 62% White and
      38% Black) who had data on CF volumes (epicardial fat [EAT], paracardial fat
      [PAT], total heart fat, and aortic perivascular fat), VAT, and BMI were studied.
      RESULTS: In models adjusted for age, study site, menopausal status, comorbid
      conditions, alcohol consumption, and physical activity, Black women had 19.8%
      less EAT, 24.5% less PAT, 20.4% less total heart fat, and 13.2% less perivascular
      fat than White women (all P < 0.001). These racial differences remained
      significant after additional adjustment for BMI or VAT. Race significantly
      modified associations between adiposity measures and CF volumes. Every 1-SD
      higher BMI was associated with 66.7% greater PAT volume in White compared with
      42.4% greater PAT volume in Black women (P = 0.004), whereas every 1-SD higher
      VAT was associated with 32.3% greater EAT volume in Black compared with 25.3%
      greater EAT volume in White women (P = 0.039). CONCLUSIONS: Racial differences
      were found in CF volumes and in their associations with adiposity measures among
      midlife women. Future research should determine how race-specific changes in CF
      volumes impact CHD risk in women.

PMID- 28763399
TI  - Factors associated with reasons incontinent midlife women report for not seeking
      urinary incontinence treatment over 9 years across the menopausal transition.
AB  - OBJECTIVE: We explored factors associated with reasons that women with urinary
      incontinence (UI) reported for not seeking treatment for their UI from a
      healthcare professional and whether reasons differed by race/ethnicity,
      socioeconomic status, or education. METHODS: We analyzed questionnaire data
      collected from 1995 to 2005 in the Study of Women's Health Across the Nation. In
      visits 7 to 9, we elicited reasons that women with UI reported for not seeking
      treatment and condensed them into: UI not bad enough, beliefs about UI causes (UI
      is a normal consequence of aging or childbirth), and motivational barriers (such
      as feeling too embarrassed). We used Generalized Estimating Equations and ordinal
      logistic regression to evaluate factors associated with these reported reasons
      and number of reasons. RESULTS: Of the 1,339 women reporting UI, 814 (61.0%)
      reported they did not seek treatment for UI. The most frequently reported reasons
      were as follows: "UI not bad enough" (73%), "UI is a normal part of aging" (53%),
      and "healthcare provider never asked" (55%). Women reporting daily UI had higher
      odds of reporting beliefs about UI causes (adjusted odds ratio UI 3.16, 95% CI
      1.64-6.11) or motivational barriers (adjusted odds ratio UI 2.36, 95% CI 1.21
      4.63) compared with women reporting less than monthly UI. We found no
      interactions by race/ethnicity, socioeconomic status, or education and UI
      characteristics in reasons that women reported for not seeking UI treatment.
      CONCLUSIONS: Over half of women who did not seek treatment for their UI reported
      reasons that could be addressed by public health and clinical efforts to make UI
      a discussion point during midlife well-women visits.

PMID- 28763400
TI  - Body composition, cardiometabolic risk factors, physical activity, and
      inflammatory markers in premenopausal women after a 10-year follow-up: a MONET
      study.
AB  - OBJECTIVE: Menopausal transition and postmenopause are usually associated with
      changes in body composition and a decrease in physical activity energy
      expenditure (PAEE). This study investigated body composition, cardiometabolic
      risk factors, PAEE, and inflammatory markers in premenopausal women after a 10
      year follow-up. METHODS: In all, 102 premenopausal women participated in the 5
      year observational longitudinal Montreal Ottawa New Emerging Team (MONET) study.
      This present substudy included 48 participants (age: 60.0 +/- 1.7 years; body
      mass index: 23.2 +/- 2.2 kg/m) 6.0 +/- 0.3 years after completion of the initial
      MONET study. Measures included body composition, waist circumference (WC),
      fasting glucose and insulin levels, insulin sensitivity (QUICKI model), plasma
      lipid levels, PAEE, and inflammatory markers. RESULTS: Compared with baseline
      measures of the MONET study, analyses revealed no significant increase in body
      weight, although there were significant increases in WC, fat mass (FM), % FM,
      total cholesterol, low-density lipoprotein cholesterol and high-density
      lipoprotein cholesterol, haptoglobin, apolipoprotein B, ferritin, adiponectin,
      and soluble cluster of differentiation 14 (all P < 0.001) after the 10-year
      follow-up. However, significant decreases were observed for fat-free mass, PAEE,
      fasting glucose levels, interleukin-8 levels, and soluble tumor necrosis factor
      receptors 1 and 2 (sTNFR-1 and sTNFR-2) levels (all P < 0.05). To determine the
      effect of postmenopausal years, data were restructured based on final menstrual
      period (FMP), and one-way analyses of variance were performed.Waist
      circumference, % FM, total cholesterol, high-density lipoprotein cholesterol,
      apolipoprotein B, ferritin, adiponectin, and soluble cluster of differentiation
      14 were higher in early and late postmenopausal periods in these women. sTNFR-1
      and sTNFR-2 levels were higher at the FMP and early postmenopausal years as
      compared with the late postmenopausal periods. Finally, interleukin-8 levels were
      lower in years after FMP. CONCLUSION: The number of years elapsed since the FMP
      can affect body composition, cardiometabolic risk factors, and inflammatory
      markers in healthy premenopausal women going through menopausal transition and
      postmenopausal periods.

PMID- 28763401
TI  - Randomized, double-blind, placebo-controlled clinical trial for evaluating the
      efficacy of fractional CO2 laser compared with topical estriol in the treatment
      of vaginal atrophy in postmenopausal women.
AB  - OBJECTIVE: The aim of the study was to evaluate efficacy of fractional CO2
      vaginal laser treatment (Laser, L) and compare it to local estrogen therapy
      (Estriol, E) and the combination of both treatments (Laser + Estriol, LE) in the
      treatment of vulvovaginal atrophy (VVA). METHODS: A total of 45 postmenopausal
      women meeting inclusion criteria were randomized in L, E, or LE groups.
      Assessments at baseline, 8 and 20 weeks, were conducted using Vaginal Health
      Index (VHI), Visual Analog Scale for VVA symptoms (dyspareunia, dryness, and
      burning), Female Sexual Function Index, and maturation value (MV) of Meisels.
      RESULTS: Forty-five women were included and 3 women were lost to follow-up. VHI
      average score was significantly higher at weeks 8 and 20 in all study arms. At
      week 20, the LE arm also showed incremental improvement of VHI score (P = 0.01).
      L and LE groups showed a significant improvement of dyspareunia, burning, and
      dryness, and the E arm only of dryness (P < 0.001). LE group presented
      significant improvement of total Female Sex Function Index (FSFI) score (P =
      0.02) and individual domains of pain, desire, and lubrication. In contrast, the L
      group showed significant worsening of pain domain in FSFI (P = 0.04), but FSFI
      total scores were comparable in all treatment arms at week 20. CONCLUSIONS: CO2
      vaginal laser alone or in combination with topical estriol is a good treatment
      option for VVA symptoms. Sexual-related pain with vaginal laser treatment might
      be of concern.

PMID- 28763403
TI  - Relative contribution of obesity and menopause to the association between serum
      adiponectin and incident metabolic syndrome.
AB  - OBJECTIVE: Metabolic syndrome is closely linked to obesity. Menopause may play a
      critical role in understanding the pathophysiology of metabolic syndrome in
      women. We investigated the relative contribution of obesity and menopause to the
      association between serum adiponectin levels and the development of metabolic
      syndrome. METHODS: A prospective cohort study was conducted in which a total of
      1,219 women without metabolic syndrome were examined at baseline (2005-2008) and
      followed up (2008-2011). Women were divided according to tertiles of serum
      adiponectin levels and menopause status, and then stratified into four groups:
      the nonobese with high adiponectin; the nonobese with low adiponectin; the obese
      with high adiponectin; and the obese with low adiponectin. RESULTS: During an
      average 2.5-year follow-up, 44 premenopausal women (9.8%) and 161 postmenopausal
      women (20.9%) developed metabolic syndrome. The obese group with low serum
      adiponectin demonstrated an increased risk for developing metabolic syndrome in
      both premenopausal (odds ratio [OR] 5.92, 95% confidence interval [CI] 2.24
      15.66) and postmenopausal women (OR 4.22, 95% CI 2.41-7.36). However, the inverse
      association between serum adiponectin levels and incidence of metabolic syndrome
      was observed in premenopausal women with obesity (OR 0.16, 95% CI 0.03-0.81), but
      not in postmenopausal women with obesity (OR 0.55, 95% CI 0.27-1.14).
      CONCLUSIONS: High serum adiponectin levels showed no inverse association with
      metabolic syndrome in postmenopausal women with obesity. These findings may
      suggest a need for closer management of metabolic risk in postmenopausal women.

PMID- 28763402
TI  - Understanding the complex relationships underlying hot flashes: a Bayesian
      network approach.
AB  - OBJECTIVE: The mechanism underlying hot flashes is not well-understood, primarily
      because of complex relationships between and among hot flashes and their risk
      factors. METHODS: We explored those relationships using a Bayesian network
      approach based on a 2006 to 2015 cohort study of hot flashes among 776 female
      residents, 45 to 54 years old, in the Baltimore area. Bayesian networks were fit
      for each outcome (current hot flashes, hot flashes before the end of the study,
      hot flash severity, hot flash frequency, and age at first hot flashes) separately
      and together with a list of risk factors (estrogen, progesterone, testosterone,
      body mass index and obesity, race, income level, education level, smoking
      history, drinking history, and activity level). Each fitting was conducted
      separately on all women and only perimenopausal women, at enrollment and 4 years
      after enrollment. RESULTS: Hormone levels, almost always interrelated, were the
      most common variable linked to hot flashes; hormone levels were sometimes related
      to body mass index, but were not directly related to any other risk factors.
      Smoking was also frequently associated with increased likelihood of severe
      symptoms, but not through an antiestrogenic pathway. The age at first hot flashes
      was related only to race. All other factors were either not related to outcomes
      or were mediated entirely by race, hormone levels, or smoking. CONCLUSIONS: These
      models can serve as a guide for design of studies into the causal network
      underlying hot flashes.

PMID- 28763404
TI  - Depression in Kidney Transplant Recipients: Prevalence, Risk Factors, and
      Association With Functional Disabilities.
AB  - This study examined the prevalence, risk factors, and disability associated with
      depression. We conducted a cross-sectional, observational study in 217
      consecutive kidney transplant (KT) recipients routinely followed-up at a Kidney
      Transplantation Clinic in Northern Thailand. Participants were assessed using the
      Charlson Comorbidity Index (CCI), the nine-item Patient Health Questionnaire (PHQ
      9), and the 12-item self-report of World Health Organization Disability
      Assessment Scale, Version 2.0 (WHODAS). Twenty-eight (12.9%) patients had
      depression (PHQ-9 score, >=10). A binary logistic regression analysis found that
      the CCI score was significantly higher in KT recipients with depression (beta =
      0.54, p < 0.01). After the adjustment of education and glomerular filter rates,
      an ordinal logistic regression analysis revealed that the PHQ-9 scores were
      positively correlated with the WHODAS scores (beta = 0.39, p < 0.01). In KT
      recipients, physical comorbidity is associated with depression, and depression is
      correlated with functional disability.

PMID- 28763405
TI  - Suspected Pediatric Influenza Risk-Stratification Algorithm: A Clinical Decision
      Tool.
AB  - BACKGROUND AND OBJECTIVES: Influenza causes significant annual burden among
      children. Current guidelines recommend empiric treatment for a broadly defined
      group of children at high risk for influenza complications, resulting in
      overtreatment or costly viral testing. This study creates an algorithm for
      clinicians to risk stratify children with influenza-like illness (ILI) according
      to likelihood of influenza infection. METHODS: A retrospective analysis was
      performed on 818 children seen in the emergency department from November 2012 to
      April 2013 for ILI. We reviewed medical records for symptoms, influenza risk
      factors, and viral assay results. Classification and regression tree analyses
      were performed separately for children older and younger than 2 years. RESULTS:
      In children younger than 2 years, populations likely to test positive were those
      with an influenza-positive contact, unimmunized children, and those presenting in
      high-incidence influenza periods. In this subgroup, immunized patients in low
      incidence seasons and those with absence of cough are low risk for influenza
      infection. For children 2 years and older, high-risk populations were unimmunized
      children, those presenting in high-incidence influenza periods and those with
      myalgia or absence of diarrhea. CONCLUSIONS: These risk-stratification analyses
      were summarized into Suspected Pediatric Influenza Risk-Stratification Algorithm
      (SPIRA). For those in whom influenza infection is likely, clinicians may consider
      empiric treatment. Conversely, patients whom SPIRA identifies as unlikely to be
      infected with influenza are candidates for viral testing and targeted treatment.
      In assessing children with ILI, SPIRA aids clinicians in determining who to test
      versus treat empirically, saving children from costly viral testing or
      unnecessary antiviral exposure.

PMID- 28763406
TI  - Massive Pericardial Effusion and Tamponade Can Be a First Sign of Familial
      Mediterranean Fever.
AB  - Cardiac involvement is a rare initial presentation of familial Mediterranean
      fever (FMF). We described 2 children with massive pericardial effusion and
      cardiac tamponade, who were later diagnosed as having FMF based on clinical and
      laboratory findings. Therefore, in children presenting with massive pericardial
      effusion, FMF should be considered as one of the differential diagnoses. In
      addition, massive pericardial effusion is a serious clinical condition that
      requires emergency therapeutic approach including pericardiocenthesis. For
      medical treatment, colchicine is the first line therapy, but in resistant cases,
      other anti-inflammatory drugs can be used for extra anti-inflammatory effect.

PMID- 28763407
TI  - Point-of-Care Ultrasound Diagnosis of Multiple Mandibular Fractures in an
      Adolescent Presenting to the Pediatric Emergency Department.
AB  - We present a case of an adolescent patient with multiple mandibular fractures
      diagnosed by point-of-care ultrasound in the pediatric emergency department.
      Sonographic findings consistent with fracture were identified in our patient, and
      early consultation expedited interdepartmental coordination and disposition. The
      role of ultrasound in identifying various traumatic orthopedic and maxillofacial
      injuries is discussed.

PMID- 28763408
TI  - Cost and Return on Investment of a Work-Family Intervention in the Extended Care
      Industry: Evidence From the Work, Family, and Health Network.
AB  - OBJECTIVE: To estimate the cost and return on investment (ROI) of an intervention
      targeting work-family conflict (WFC) in the extended care industry. METHODS:
      Costs to deliver the intervention during a group-randomized controlled trial were
      estimated, and data on organizational costs-presenteeism, health care costs,
      voluntary termination, and sick time-were collected from interviews and
      administrative data. Generalized linear models were used to estimate the
      intervention's impact on organizational costs. Combined, these results produced
      ROI estimates. A cluster-robust confidence interval (CI) was estimated around the
      ROI estimate. RESULTS: The per-participant cost of the intervention was $767. The
      ROI was -1.54 (95% CI: -4.31 to 2.18). The intervention was associated with a
      $668 reduction in health care costs (P < 0.05). CONCLUSIONS: This paper builds
      upon and expands prior ROI estimation methods to a new setting.

PMID- 28763409
TI  - Functional and Clinical Outcomes of Nonsurgically Managed Tibial Plateau
      Fractures.

PMID- 28763410
TI  - Risk Factors for Prolonged Opioid Use Following Spine Surgery, and the
      Association with Surgical Intensity, Among Opioid-Naive Patients.
AB  - BACKGROUND: There is a growing concern that the use of prescription opioids
      following surgical interventions, including spine surgery, may predispose
      patients to chronic opioid use and abuse. We sought to estimate the proportion of
      patients using opioids up to 1 year after discharge following common spinal
      surgical procedures and to identify factors associated with sustained opioid use.
      METHODS: This study utilized 2006 to 2014 data from TRICARE insurance claims
      obtained from the Military Health System Data Repository. Adults who underwent 1
      of 4 common spinal surgical procedures (discectomy, decompression, lumbar
      posterolateral arthrodesis, or lumbar interbody arthrodesis) were identified.
      Patients with a history of opioid use in the 6 months preceding surgery were
      excluded. Posterolateral arthrodesis and interbody arthrodesis were considered
      procedures of high intensity, and discectomy and decompression, low intensity.
      Covariates included demographic factors, preoperative diagnoses, comorbidities,
      postoperative complications, and mental health disorders. Risk-adjusted Cox
      proportional hazard models were used to evaluate the time to opioid
      discontinuation. RESULTS: This study included 9,991 patients. Eighty-four percent
      filled at least 1 opioid prescription on discharge. At 30 days following
      discharge, 8% continued opioid use; at 3 months, 1% continued use; and at 6
      months, 0.1%. In the adjusted analysis, the low-intensity surgical procedures
      were associated with a higher likelihood of discontinuing opioid use (discectomy:
      hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.36 to 1.50; and
      decompression: HR = 1.34, 95% CI = 1.25 to 1.43). Depression (HR = 0.84, 95% CI =
      0.77 to 0.90) was significantly associated with a decreased likelihood of
      discontinuing opioid use (p < 0.001). CONCLUSIONS: By 6 months following
      discharge, nearly all patients had discontinued opioid use after spine surgery.
      As only 0.1% of the patients continued opioid use at 6 months following surgery,
      these results indicate that spine surgery among opioid-naive patients is not a
      major driver of long-term prescription opioid use. Socioeconomic status and pre
      existing mental health disorders may be factors associated with sustained opioid
      use following spine surgery. LEVEL OF EVIDENCE: Therapeutic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 28763411
TI  - Patient Decision Aids Improve Decision Quality and Patient Experience and Reduce
      Surgical Rates in Routine Orthopaedic Care: A Prospective Cohort Study.
AB  - BACKGROUND: Patient decision aids are effective in randomized controlled trials,
      yet little is known about their impact in routine care. The purpose of this study
      was to examine whether decision aids increase shared decision-making when used in
      routine care. METHODS: A prospective study was designed to evaluate the impact of
      a quality improvement project to increase the use of decision aids for patients
      with hip or knee osteoarthritis, lumbar disc herniation, or lumbar spinal
      stenosis. A usual care cohort was enrolled before the quality improvement project
      and an intervention cohort was enrolled after the project. Participants were
      surveyed 1 week after a specialist visit, and surgical status was collected at 6
      months. Regression analyses adjusted for clustering of patients within clinicians
      and examined the impact on knowledge, patient reports of shared decision-making
      in the visit, and surgical rates. With 550 surveys, the study had 80% to 90%
      power to detect a difference in these key outcomes. RESULTS: The response rates
      to the 1-week survey were 70.6% (324 of 459) for the usual care cohort and 70.2%
      (328 of 467) for the intervention cohort. There was no significant difference (p
      > 0.05) in any patient characteristic between the 2 cohorts. More patients
      received decision aids in the intervention cohort at 63.6% compared with the
      usual care cohort at 27.3% (p = 0.007). Decision aid use was associated with
      higher knowledge scores, with a mean difference of 18.7 points (95% confidence
      interval [CI], 11.4 to 26.1 points; p < 0.001) for the usual care cohort and 15.3
      points (95% CI, 7.5 to 23.0 points; p = 0.002) for the intervention cohort.
      Patients reported more shared decision-making (p = 0.009) in the visit with their
      surgeon in the intervention cohort, with a mean Shared Decision-Making Process
      score (and standard deviation) of 66.9 +/- 27.5 points, compared with the usual
      care cohort at 62.5 +/- 28.6 points. The majority of patients received their
      preferred treatment, and this did not differ by cohort or decision aid use.
      Surgical rates were lower in the intervention cohort for those who received the
      decision aids at 42.3% compared with 58.8% for those who did not receive decision
      aids (p = 0.023) and in the usual care cohort at 44.3% for those who received
      decision aids compared with 55.7% for those who did not receive them (p = 0.45).
      CONCLUSIONS: The quality improvement project successfully integrated patient
      decision aids into a busy orthopaedic clinic. When used in routine care, decision
      aids are associated with increased knowledge, more shared decision-making, and
      lower surgical rates. CLINICAL RELEVANCE: There is increasing pressure to design
      systems of care that inform and involve patients in decisions about elective
      surgery. In this study, the authors found that patient decision aids, when used
      as part of routine orthopaedic care, were associated with increased knowledge,
      more shared decision-making, higher patient experience ratings, and lower
      surgical rates.

PMID- 28763412
TI  - Plate Versus Tension-Band Wire Fixation for Olecranon Fractures: A Prospective
      Randomized Trial.
AB  - BACKGROUND: The aim of this single-center, single-blinded, prospective randomized
      trial was to compare the outcomes of tension-band wire (TBW) and plate fixation
      for simple isolated, displaced fractures of the olecranon. METHODS: We performed
      a prospective randomized trial involving 67 patients who were >=16 to <75 years
      of age and had an acute isolated, displaced fracture of the olecranon. Patients
      were randomized to either TBW (n = 34) or plate fixation (n = 33) and were
      evaluated at 6 weeks, 3 months, 6 months, and 1 year following surgery. The
      primary outcome measure was the Disabilities of the Arm, Shoulder and Hand (DASH)
      score at 1 year. RESULTS: The baseline demographic and fracture characteristics
      of the 2 groups were comparable, except for age, which was lower in the TBW
      group. The 1-year follow-up rate was 85% (n = 57), with 84% (n = 56) completing
      the DASH. There was a significant improvement in the DASH score over the 1-year
      period following surgery (p < 0.001). At 1 year, the DASH score for the TBW group
      (12.8) did not differ significantly from that of the plate group (8.5) (p =
      0.315). The groups also did not differ significantly in terms of range of motion,
      the Broberg and Morrey score, the Mayo Elbow Score, or the DASH at all assessment
      points over the 1 year (all p >= 0.05). Complication rates were significantly
      higher in the TBW group (63% compared with 38%; p = 0.042), predominantly because
      of a significantly higher rate of metalwork removal in symptomatic patients
      (50.0% compared with 22%; p = 0.021). Four infections occurred, all in the plate
      group (0% versus 13%; p = 0.114), as did 3 revision surgeries (0% versus 9.4%; p
      = 0.238). CONCLUSIONS: Among active patients with a simple isolated, displaced
      fracture of the olecranon, no difference was found between TBW and plate fixation
      in the patient-reported outcome at 1 year following surgery. The complication
      rate was higher following TBW fixation and was due to a higher rate of implant
      removal in symptomatic patients. However, the more serious complications of
      infection and the need for revision surgery occurred exclusively following plate
      fixation in this trial. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 28763413
TI  - Ultrasound-Guided Motor-Sparing Knee Blocks for Postoperative Analgesia Following
      Total Knee Arthroplasty: A Randomized Blinded Study.
AB  - BACKGROUND: Pain following total knee arthroplasty (TKA) is often severe and can
      inhibit rehabilitation. Motor-sparing analgesic techniques such as periarticular
      infiltrations and adductor canal blocks have been popularized for knee analgesia
      since they preserve motor strength and permit early mobilization. Our primary
      objective was to compare the duration of analgesia from motor-sparing blocks with
      that of a standard periarticular infiltration. We used the time to first rescue
      analgesia as the end point. METHODS: We randomized 82 patients scheduled for
      elective TKA to receive either the preoperative motor-sparing block (0.5%
      ropivacaine, 2.5 MUg/mL of epinephrine, 10 mg of morphine, and 30 mg of
      ketorolac) or intraoperative periarticular infiltration (0.3% ropivacaine, 2.5
      MUg/mL of epinephrine, 10 mg of morphine, and 30 mg of ketorolac). For the motor
      sparing block, we modified the ultrasound-guided adductor canal block by
      combining it with a lateral femoral cutaneous nerve block and posterior knee
      infiltration. The patients, surgeons, anesthetists administering the blocks, and
      outcome assessors all remained blinded to group allocation. Our primary outcome
      was duration of analgesia (time to first rescue analgesia). Secondary outcomes
      included quadriceps strength, function, side effects, satisfaction, and length of
      hospital stay. RESULTS: The duration of analgesia was significantly longer (mean
      difference, 8.8 hours [95% confidence interval = 3.98 to 13.62], p < 0.01) for
      the motor-sparing-block group (mean [and standard error], 18.1 +/- 1.7 hours)
      compared with the periarticular infiltration group (mean, 9.25 +/- 1.7 hours).
      The infiltration group had significantly higher scores for pain at rest for the
      first 2 postoperative hours and for pain with knee movement at 2 and 4 hours.
      There were no significant differences between groups with regard to any other
      secondary outcomes. CONCLUSIONS: In patients undergoing a TKA, a motor-sparing
      block provides longer analgesia than periarticular infiltration with retention of
      quadriceps muscle strength, function, patient satisfaction, and a short hospital
      stay. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 28763414
TI  - Capitellar Fractures in Children and Adolescents: Classification and Early
      Results of Treatment.
AB  - BACKGROUND: There has been limited published information regarding capitellar
      fractures in the pediatric population. The purpose of this investigation was to
      characterize capitellar fracture patterns in children and adolescents and to
      assess early clinical and radiographic treatment outcomes. METHODS: A
      retrospective analysis of 37 children and adolescents with capitellar fractures
      presenting to a tertiary pediatric hospital from 2004 to 2014 was performed. The
      mean patient age at the time of injury was 11.8 years. Medical records and
      radiographs were evaluated for fracture pattern, treatment, healing, and
      complications. Fractures were categorized on the basis of prevailing patterns of
      injury, and a classification system is proposed that aids in treatment decision
      making. Thirty-two patients had follow-up of at least 6 weeks and were included
      for assessment of treatment outcomes. The mean follow-up was 12.3 months.
      RESULTS: Three predominant capitellar fracture patterns were identified. Type-I
      fractures (n = 25) were anterior shear injuries. Nondisplaced anterior shear
      fractures were successfully treated with cast immobilization. Displaced anterior
      shear fractures were treated with open reduction and internal fixation, with good
      results in a majority of patients. Of the 21 patients with Type-Ib fractures
      eligible for analysis, 6 (29%) required a secondary surgical procedure for loss
      of motion related to soft-tissue contracture, osteonecrosis, implant prominence,
      and/or intra-articular loose bodies. Type-II fractures (n = 9) were
      posterolateral shear injuries, typically associated with ulnohumeral
      dislocations. Among 5 patients with displaced fractures and adequate follow-up, 3
      patients were treated nonoperatively and had poor results, with loss of elbow
      motion or mechanical symptoms, and 2 patients were treated surgically and
      achieved good functional restoration. Type-III fractures (n = 3) were acute
      chondral shear injuries, which achieved full restoration of motion after surgical
      treatment. CONCLUSIONS: A classification of pediatric capitellar fractures is
      proposed, guiding treatment and prognosis. Nondisplaced fractures heal
      successfully with cast immobilization. Good results may be expected with surgical
      fixation of displaced Type-I fractures (anterior shear). Type-II fractures
      (posterolateral shear) and Type-III fractures (chondral shear) are more subtle;
      advanced imaging and timely surgical management for displaced injuries are
      recommended to optimize clinical results. LEVEL OF EVIDENCE: Therapeutic Level
      IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 28763415
TI  - Clinical and Radiographic Outcomes of the Ream-and-Run Procedure for Primary
      Glenohumeral Arthritis.
AB  - BACKGROUND: The ream-and-run procedure can provide improvement in shoulder
      function and comfort for selected patients with primary glenohumeral arthritis
      who wish to avoid a prosthetic glenoid component. The purpose of this study was
      to evaluate factors associated with medialization of the humeral head after this
      procedure as well as the relationship of medialization to the clinical outcome.
      METHODS: We collected patient, shoulder, and procedure characteristics along with
      Simple Shoulder Test (SST) scores before surgery and at the time of follow-up.
      Medialization was determined by comparing the position of the humeral head
      prosthesis in relation to the scapula on postoperative baseline radiographs made
      within 6 weeks after surgery with that on comparable follow-up radiographs made
      >=18 months after surgery. RESULTS: Two-year clinical outcomes were available for
      101 patients (95% were male). Comparable radiographs at postoperative baseline
      and follow-up evaluations were available for 50 shoulders. For all patients, the
      mean SST score (and standard deviation) increased from 4.9 +/- 2.8 preoperatively
      to 10.3 +/- 2.4 at the latest follow-up (p < 0.001). Significant clinical
      improvement was observed for glenoid types A2 and B2. Shoulders with a type-A2
      glenoid morphology, with larger preoperative scapular body-glenoid angles, and
      with lower preoperative SST scores, were associated with the greatest clinical
      improvement. Clinical outcome was not significantly associated with the amount of
      medialization. CONCLUSIONS: The ream-and-run procedure can be an effective
      treatment for advanced primary glenohumeral osteoarthritis in active patients.
      Further study will be necessary to determine whether medialization affects the
      clinical outcome with follow-up of >2 years. LEVEL OF EVIDENCE: Therapeutic Level
      IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 28763417
TI  - Sport and Sex-Specific Reporting Trends in the Epidemiology of Concussions
      Sustained by High School Athletes.
AB  - BACKGROUND: Approximately 300,000 U.S. adolescents sustain concussions annually
      while participating in organized athletics. This study aimed to track sex and
      sport-specific trends among high school sports-related concussions over time, to
      identify whether a particular sport predisposes athletes to a higher risk, and to
      assess whether traumatic brain injury law enactments have been successful in
      improving recognition. METHODS: Injury data for academic years 2005 to 2014 were
      collected from annual reports generated by High School RIO (Reporting Information
      Online). The relative proportions of total estimated concussions to total
      estimated injuries were compared using an injury proportion ratio. The concussion
      rate was defined as the number of concussions per 10,000 athlete exposures (1
      athlete participating in 1 practice or competition), with rates compared using a
      rate ratio. To evaluate the impact of legislation on sports-related concussions
      in this population, trends in concussion rates and proportions were analyzed
      before enactment (academic years 2005-2009) and after enactment (academic years
      2010-2014). RESULTS: Between 2005-2006 and 2014-2015, a significant increase (p <
      0.0001) in the overall number of concussions for all sports combined, the overall
      concussion rate (rate ratio, 2.30 [95% confidence interval, 2.04 to 2.59]), and
      the overall proportion of concussions (injury proportion ratio, 2.68 [95%
      confidence interval, 2.66 to 2.70]) was seen. Based on the injury proportion
      ratio, during the 2014-2015 academic year, concussions were more common in girls'
      soccer than in any other sport (p < 0.0001). CONCLUSIONS: Because of potentially
      devastating consequences, concussion prevention and recognition measures continue
      to be emphasized in high school contact sports. The data in our study suggest
      that significant increases in the overall rate and proportion of reported
      concussions during the past decade could have been affected by traumatic brain
      injury legislation. To our knowledge, this is the first study to show that girls'
      soccer players may have an even greater risk of sustaining a concussion than all
      other sports. CLINICAL RELEVANCE: Sports-related concussions in adolescent
      athletes can have devastating consequences, and we now know that female athletes,
      especially girls' soccer players, may be at an even greater risk for sustaining
      this injury than all other athletes. Knowledge of the trends identified by this
      study may help lead to policy and prevention measures that can accommodate each
      sport effectively and potentially halt these trends.

PMID- 28763416
TI  - The CD45lowCD271high Cell Prevalence in Bone Marrow Samples May Provide a Useful
      Measurement of the Bone Marrow Quality for Cartilage and Bone Regenerative
      Therapy.
AB  - BACKGROUND: Bone marrow aspirates and concentrates are increasingly being used
      for musculoskeletal regenerative therapies, providing bone and cartilage
      progenitors. However, the quality of these bone marrow samples remains imprecise
      within clinical settings. As there is a need for the development of these
      therapies, a method of counting CD45CD271 cells was optimized and tested as an
      indicator of bone marrow sample quality. METHODS: Bone marrow aspirates were
      collected from 54 donors (28 male and 26 female; median age of 48 years). The
      reagent concentrations were optimized for fast staining, and an acoustic-focusing
      flow cytometer (Attune) was used to enable automated CD45CD271 cell counting in
      bone marrow aspirates, bone marrow concentrates, and samples loaded onto a
      collagen scaffold. The CD45CD271 cell counts were compared with those obtained
      using another flow-cytometry-based method (LSR II) and with connective tissue
      progenitor (CTP) counts quantified using a colony forming unit-fibroblast (CFU-F)
      assay. RESULTS: The optimized method enabled the counting of CD45CD271 cells
      within only 15 minutes. The quantified cell counts (median, 1,520; range, 96 to
      20,992 cells/mL of bone marrow) were positively correlated with the CTP counts (p
      < 0.0001; r = 0.7237). In agreement with CFU-F and LSR II-based assays, the
      CD45CD271 cell counts quantified using the Attune-based method decreased with age
      in the samples from female but not male donors (p = 0.0015 and p = 0.3877,
      respectively). A significant increase in CD45CD271 cell counts was detected
      following bone marrow concentration (mean, 5-fold; 95% confidence interval [CI],
      3.6 to 7.2-fold). Additionally, the number of CD45CD271 cells attached to the
      collagen scaffold was positively correlated with the number of progenitor cells
      that survived on the scaffold after 2-week culture (p = 0.0348). CONCLUSIONS: An
      assay for counting CD45CD271 cells may provide a useful measurement of bone
      marrow quality. While the specificity of this measurement of CD45CD271 cells
      remained low in our experimental conditions, CD45CD271 cell counts were
      positively and modestly correlated with the prevalence of CTPs. CLINICAL
      RELEVANCE: A fast and automated assessment of bone marrow aspirate/concentrate
      quality using CD45CD271 cell counting may be a useful tool for improving the
      quality of regenerative therapy.

PMID- 28763419
TI  - What's Important: Giving Back.

PMID- 28763418
TI  - Tracking Cumulative Radiation Exposure in Orthopaedic Surgeons and Residents:
      What Dose Are We Getting?
AB  - BACKGROUND: The purpose of this study was to determine the amount of cumulative
      radiation exposure received by orthopaedic surgeons and residents in various
      subspecialties. We obtained dosimeter measures over 12 months on 24 residents and
      16 attending surgeons. METHODS: Monthly radiation exposure was measured over a 12
      month period for 24 orthopaedic residents and 16 orthopaedic attending surgeons.
      The participants wore a Landauer Luxel dosimeter on the breast pocket of their
      lead apron. The dosimeters were exchanged every rotation (5 to 7 weeks) for the
      resident participants and every month for the attending surgeon participants.
      Radiation exposure was compared by orthopaedic subspecialty, level of training,
      and type of fluoroscopy used (regular C-arm compared with mini C-arm). RESULTS:
      Orthopaedic residents participating in this study received monthly mean radiation
      exposures of 0.2 to 79 mrem/month, lower than the dose limits of 5,000 mrem/year
      recommended by the United States Nuclear Regulatory Commission (U.S. NRC). Senior
      residents rotating on trauma were exposed to the highest monthly radiation (79
      mrem/month [range, 15 to 243 mrem/month]) compared with all other specialty
      rotations (p < 0.001). Similarly, attending orthopaedic surgeons who specialize
      in trauma or deformity surgery received the highest radiation exposure of their
      peers, and the mean exposure was 53 mrem/month (range, 0 to 355 mrem/month).
      CONCLUSIONS: Residents and attending surgeons performing trauma or deformity
      surgical procedures are exposed to significantly higher doses of radiation
      compared with all other subspecialties within orthopaedic surgery, but the doses
      are still within the recommended limits. CLINICAL RELEVANCE: The use of ionizing
      radiation in the operating room has become an indispensable part of orthopaedic
      surgery. Although all surgeons in our study received lower than the yearly
      recommended dose limit, it is important to be aware of how much radiation we are
      exposed to as surgeons and to take measures to further limit that exposure.

PMID- 28763420
TI  - Patients with Staged Bilateral Total Joint Arthroplasty in Registries: Immortal
      Time Bias and Methodological Options.
AB  - BACKGROUND: In arthroplasty data, patients with staged bilateral total joint
      arthroplasty (TJA) pose a problem in statistical analysis. Subgroup analysis, in
      which patients with unilateral and bilateral TJA are studied separately, is
      sometimes considered an appropriate solution to the problem; we aim to show that
      this is not true because of immortal time bias. METHODS: We reviewed patients who
      underwent staged (at any time) bilateral TJA. The logical fallacy leading to
      immortal time bias is explained through a simple artificial data example. The
      cumulative incidences of revision and death are computed by subgroup analysis and
      by landmark analysis based on hip replacement data from the Dutch Arthroplasty
      Register and on simulated data sets. RESULTS: For patients who underwent
      unilateral TJA, subgroup analysis can lead to an overestimate of the cumulative
      incidence of death and an underestimate of the cumulative incidence of revision.
      The reverse conclusion holds for patients who underwent staged bilateral TJA.
      Analysis of these patients can lead to an underestimate of the cumulative
      incidence of death and an overestimate of the cumulative incidence of revision.
      Immortal time bias can be prevented by using landmark analysis. CONCLUSIONS: When
      examining arthroplasty registry data, patients who underwent staged bilateral TJA
      should be analyzed with caution. An appropriate statistical method to address the
      research question should be selected.

PMID- 28763422
TI  - In Spite of Limited Generalizability, New Findings Reinforce the Lesson That Long
      Term Opioid Use Is Not Attributable to Surgical Pain: Commentary on an article by
      Andrew J. Schoenfeld, MD, MSc, et al.: "Risk Factors for Prolonged Opioid Use
      Following Spine Surgery, and the Association with Surgical Intensity, Among
      Opioid-Naive Patients".

PMID- 28763421
TI  - Filling the Pipeline: AOA Critical Issues.
AB  - This is the Presidential Address, "Filling the Pipeline," that was given by
      Sanford E. Emery, MD, MBA, at the Annual Meeting of the American Orthopaedic
      Association in June 2016.

PMID- 28763423
TI  - Revisiting the Socket: Commentary on an article by Jeremy S. Somerson, MD, et
      al.: "Clinical and Radiographic Outcomes of the Ream-and-Run Procedure for
      Primary Glenohumeral Arthritis".

PMID- 28763424
TI  - Congenital Cytomegalovirus Infection After a Multiple Birth Pregnancy.
AB  - BACKGROUND: Congenital cytomegalovirus (cCMV) infection is an important cause of
      hearing loss and neurodevelopment delay. While data on vertical transmission and
      neonatal outcome after singleton pregnancy with cCMV are well established, only
      scarce reports have addressed cCMV in multiple birth pregnancies. Furthermore, no
      studies have yet compared the outcome after birth and long-term follow-up of
      children with cCMV born after a singleton versus multiple pregnancies. METHODS:
      Infant outcome after birth of symptomatic versus asymptomatic infection was
      compared for infants born with cCMV after multiple (study group) and singleton
      (control group) pregnancies in a 1:2 ratio. RESULTS: Of 508 infants diagnosed
      with cCMV, 25 (4.9%) were born after a multiple pregnancy. Children in the study
      and control groups did not differ in terms of specific prenatal CMV
      investigations including amniocentesis and brain magnetic resonance imaging
      studies. However, prematurity rates were significantly higher in the study
      compared with control group (52% vs. 4%, P < 0.001). There was a higher rate of
      symptomatic cCMV infection in the study group than in the controls (48% vs. 14%,
      P < 0.001). Hearing impairment at birth was also more frequent in the study group
      (32% vs. 8%, P = 0.016). A long-term follow-up demonstrated that children in the
      study group had higher rates of neurologic sequelae (hearing impairment or
      neurodevelopmental delay) compared with children in the control group (20% vs.
      4%, P = 0.016). CONCLUSIONS: Infants with cCMV born after multiple birth
      pregnancies are born earlier and have a higher risk of symptomatic disease at
      birth and worse long-term neurologic outcome than those born after a singleton
      pregnancy. This important group of children warrants meticulous prenatal and
      postnatal care.

PMID- 28763425
TI  - Frequency of Acute Otitis Media in Children Under 24 Months of Age Before and
      After the Introduction of the 10-valent Pneumococcal Conjugate Vaccine Into the
      National Immunization Program in Chile.
AB  - BACKGROUND: Streptococcus pneumoniae is the leading cause of acute otitis media
      (AOM). Ten-valent pneumococcal conjugated vaccine (PCV-10) was introduced to the
      Chilean National Immunization Program (NIP) in 2011. The aim of this study was to
      estimate the frequency of AOM in children <24 months of age attending the
      emergency department (ED) of Hospital Sotero del Rio (HSR) 4 years before and 4
      years after the introduction of PCV-10 in the Chilean NIP. METHODS: Register
      based nested case-control study. Cases (n = 1907) were all children <24 months of
      age with a clinical diagnosis discharge of AOM at the ED of HSR, and controls (n
      = 244,334) were all other children <24 months of age attended at the same ED in
      the same time period, with any other discharge diagnosis. The data were obtained
      through HSR Statistical Service. RESULTS: In the study period, there was a mean
      of 30,695 children <24 months managed each year at the ED of HSR. The percentage
      with AOM in the prevaccine period was 0.94% and in the postvaccine period was
      0.62%, respectively (P = 0.026). Exposure to the PCV-10 was associated with a
      decreased risk to develop AOM in children <24 months, with an odds ratio of 0.659
      (95% confidence interval: 0.60-0.72). CONCLUSIONS: Our study showed a significant
      decrease in the percentage and risk of AOM in children <24 months of age who
      visited the ED of HSR after implementation of PCV-10 in the NIP in Chile.

PMID- 28763426
TI  - Epidemiology of Sepsis-like Illness in Young Infants: Major Role of Enterovirus
      and Human Parechovirus.
AB  - BACKGROUND: Sepsis-like illness is a main cause for hospital admission in young
      infants. Our aim was to investigate incidence, epidemiology and clinical
      characteristics of enterovirus (EV) and human parechovirus (HPeV) infections in
      young infants with sepsis-like illness. METHODS: This is a prospective
      observational cohort study in which infants younger than 90 days of age,
      presenting with sepsis-like symptoms in a secondary care children's hospital,
      underwent a full sepsis work-up. Clinical signs and infectious indices were
      recorded. EV or HPeV RNA was detected by polymerase chain reaction in plasma
      and/or cerebrospinal fluid (CSF). RESULTS: Infants were diagnosed with EV, HPeV,
      fever of unknown origin or severe infection. EV and HPeV were detected in 132 of
      353 (37%) and 52 of 353 (15%) of cases, respectively. EV and HPeV have distinct
      seasonability. Some differences in clinical signs and symptoms occurred between
      children with EV and HPeV infection but were of limited clinical value. CSF
      pleocytosis occurred in 44% of EV positive infants, and only in 13% of those with
      HPeV infection. CONCLUSIONS: EV and HPeV infections are major causes of sepsis
      like illness in infants < 90 days of age. Neither clinical characteristics nor
      laboratory indices were predictive for EV/HPeV infection. CSF pleocytosis occurs,
      but not in all patients. Testing for EV and HPeV in all young infants with sepsis
      like illness is strongly advised.

PMID- 28763427
TI  - Safety of Outpatient Parenteral Antimicrobial Therapy in Children.
AB  - BACKGROUND AND OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT)
      provides numerous benefits but may pose unique risks in children. We aimed to
      determine rates of OPAT antimicrobial- and intravenous access-related
      complications and their associations with specific antimicrobials and type of
      intravenous access in pediatric patients. METHODS: Observational cohort study of
      patients receiving OPAT from August 2008 to May 2015 cared for by the Infectious
      Diseases service at a tertiary children's hospital. Primary outcome was
      antimicrobial discontinuation (AD) because of OPAT-associated complications.
      Secondary outcomes were unplanned outpatient healthcare visits and readmissions
      from OPAT-associated complications. RESULTS: Seven hundred and seven intravenous
      antimicrobials were prescribed in 540 cases. Nondevice-associated musculoskeletal
      infection was the most common diagnosis (39%). Ceftriaxone (30%), cefazolin (27%)
      and vancomycin (22%) were the most commonly used antimicrobials. Complications
      led to AD, >=1 unplanned outpatient healthcare visit and >=1 readmission in 23%,
      30% and 17% of cases, respectively. Compared with use of ceftriaxone, use of
      oxacillin was associated with a significantly higher risk of AD because of any
      antimicrobial-related complication [hazard ratio (HR), 3.3; 95% confidence
      interval (CI): 1.2-9.7) and because of hepatic transaminitis (HR, 32.8; 95% CI:
      4.02-268.2). Subjects treated with intravenous clindamycin (HR, 2.6; 95% CI: 1.1
      5.8) and with a peripherally inserted central catheter (HR, 2.6; 95% CI: 1.04
      6.3) were more likely to have unplanned outpatient visits. CONCLUSIONS: Use of
      oxacillin during OPAT was associated with higher rate of AD. Patients treated
      with clindamycin and those with a peripherally inserted central catheter had
      higher rates of unplanned outpatient visits. Providers should strongly consider
      alternative treatment options when possible.

PMID- 28763428
TI  - CMV Infection in Pediatric Severe Ulcerative Colitis - A Multicenter Study from
      the Pediatric IBD Porto Group of ESPGHAN.
AB  - BACKGROUND: Data on the clinical course and outcomes of pediatric patients with
      cytomegalovirus (CMV) infection complicating acute severe ulcerative colitis
      (ASC) are very limited. The aim of our study was to compare outcomes of children
      with ASC who were CMV-positive or CMV-negative. METHODS: This was a multicenter
      retrospective case-controlled study, from centers affiliated with the Pediatric
      IBD Porto Group of ESPGHAN. We included CMV -positive children hospitalized for
      ASC and compared their colectomy rate during hospitalization and up to 1 year
      thereafter, matched with CMV-negative controls. RESULTS: A total of 56 children
      were included; 15 CMV-positive and 41 CMV-negative. More CMV-positive patients
      were resistant to intravenous corticosteroids as compare to CMV negative (93% and
      56% respectively, p=0.009). Fourteen of the CMV-positive children (93%) were
      treated with ganciclovir (5/14 (36%) with 5mg/kg and 9/14 (64%) with 10mg/kg).
      During hospitalization, 3 (20%) CMV-positive and 3 (7.8%) CMV-negative patients
      required colectomy (p=0.17). By 12 months, 5 (33%) and 5 (13%) CMV-positive and
      negative patients required colectomy, respectively (p=0.049); the significance
      was not retained on multivariate analysis. CONCLUSIONS: A higher prevalence of
      CMV-positivity was found in pediatric UC patients who required colectomy within
      12 months of hospitalization for ASC. Further studies are needed to clarify the
      impact of CMV infection on the outcome of acute severe colitis in pediatric
      patients.

PMID- 28763429
TI  - Genome-wide association study of cardiotoxicity in the NCCTG N9831 (Alliance)
      adjuvant trastuzumab trial.
AB  - OBJECTIVES: The major clinical side effect of the ERBB2-targeted breast cancer
      therapy, trastuzumab, is a decline in the left ventricular ejection fraction
      (LVEF). Improved markers are needed to better identify patients susceptible to
      cardiotoxicity. METHODS: The NCCTG N9831 trial compared adjuvant doxorubicin and
      cyclophosphamide followed by either weekly paclitaxel (arm A); paclitaxel then
      trastuzumab (arm B); or concurrent paclitaxel and trastuzumab (arm C) in patients
      with HER2-positive breast cancer. A genome-wide association study was performed
      on all patients with available DNA (N=1446). We used linear regression to
      identify single nucleotide polymorphisms (SNPs) associated with decline in LVEF,
      adjusting for age, baseline LVEF, antihypertensive medications, and the first two
      principle components. RESULTS: In total, 618 863 SNPs passed quality control and
      DNA from 1191 patients passed genotyping quality control and were identified as
      Whites of non-Hispanic origin. SNPs at six loci were associated with a decline in
      LVEF (P=7.73*10 to 8.93*10), LDB2, BRINP1, chr6 intergenic, RAB22A, TRPC6, and
      LINC01060, in patients who received chemotherapy plus trastuzumab (arms BC,
      N=800). None of these loci were significant in patients who received chemotherapy
      only (arm A, N=391) and did not increase in significance in the combined analysis
      of all patients. We did not observe association, P<0.05, with SNPs previously
      associated with trastuzumab-induced cardiotoxicity at ERBB2, I655V, and P1170A.
      We replicated association, P<0.05, with SNPs previously associated with
      anthracycline-induced cardiotoxicity at CBR3 and ABCB1. CONCLUSION: Our study
      identified six putative novel cardiotoxicity loci in patients treated with
      combination chemotherapy and trastuzumab that require further investigation and
      confirmed known associations of anthracycline-induced cardiotoxicity.

PMID- 28763430
TI  - The Usefulness of Individual-Level HIV Surveillance Data to Initiate Statewide
      HIV Partner Services: Experiences From Hawaii and New Mexico.
AB  - CONTEXT: Partner services are a broad array of services that should be offered to
      persons with human immunodeficiency virus (HIV) and that are based on a process
      through which HIV-infected persons are interviewed to elicit information about
      their sex and needle-sharing partners. Human immunodeficiency virus testing of
      partners can result in a high yield of newly diagnosed HIV positivity, but
      despite this yield and the benefits of partners knowing their exposures and HIV
      status, partner services are often not conducted. OBJECTIVE: We sought to
      determine the newly diagnosed HIV positivity and benefits to 2 health departments
      that conducted demonstration projects that focused on statewide HIV partner
      services. DESIGN: The main sources of information used for this case study
      analysis included the health department funding applications, progress reports
      and final reports submitted to the Centers for Disease Control and Prevention,
      and records of communications between Centers for Disease Control and Prevention
      and the health departments. Required quantitative reporting included the number
      of partners tested and the number of partners with newly diagnosed confirmed HIV
      infection. Required qualitative reporting included how health departments
      benefited from their demonstration project activities. SETTING: Hawaii and New
      Mexico. PARTICIPANTS: Sex and needle-sharing partners of persons who were newly
      diagnosed with HIV infection. INTERVENTION: The use of HIV surveillance data to
      initiate statewide HIV partner services. MAIN OUTCOME MEASURE: Newly diagnosed
      HIV positivity. RESULTS: During 2012-2015, the newly diagnosed HIV positivity
      among partners was 18% (78/427): 16% (17/108) in Hawaii and 19% (61/319) in New
      Mexico. The health departments benefited from improved collaborations among HIV
      prevention program and surveillance staff and among the health departments,
      providers, and AIDS service organizations. CONCLUSIONS: Hawaii and New Mexico
      each achieved a high newly diagnosed HIV positivity and benefited from improved
      local collaborations. As a result of the success of these projects, both health
      departments have continued the activities since the end of category C funding by
      securing alternative funding sources.

PMID- 28763431
TI  - E-Media Use and Preferences for Physical Activity and Public Health Information:
      Results of a Web-Based Survey.
AB  - CONTEXT: As social media (eg, Twitter) continues to gain widespread popularity,
      health research and practice organizations may consider combining it with other
      electronic media (e-media) channels (eg, Web sites, e-newsletters) within their
      communication plans. However, little is known about added benefits of using
      social media when trying to reach public health audiences about physical
      activity. OBJECTIVE: Learn about current use and preference for e-media
      communication channels among physical activity researchers and practitioners.
      DESIGN: A Web-based survey was used, open for responses from August 20, 2015,
      through January 5, 2016. Survey participation was voluntary and anonymous. The
      survey was advertised through multiple channels targeting physical activity
      researchers and practitioners, including announcements on professional listservs
      and in e-newsletters, Twitter, and posts on Facebook pages of public health
      organizations. SETTING AND PARTICIPANTS: A total of 284 survey respondents had
      complete data. MAIN OUTCOME MEASURES: Typical use of e-media to receive, seek
      out, and share information about physical activity and health and what appeals to
      researchers and practitioners for professional use. RESULTS: Most respondents
      preferred non-social media channels to social media and these preferences did not
      differ widely when examining subgroups such as researchers versus practitioners
      or social media users versus nonusers. There were few differences by respondent
      demographics, though younger respondents reported using social media more than
      older respondents. However, limiting analyses to respondents who identified as
      social media users, only about 1% of respondents ranked social media sources as
      their preferred channels for information; thus, most people would continue to be
      reached if communication remained largely via non-social media e-media channels.
      CONCLUSIONS: The present study supports growing evidence that careful surveying
      of a target audience should be undertaken when considering new communication
      channels, as preference and use may not support the effort required to create and
      maintain resource-intensive strategies like social media.

PMID- 28763432
TI  - Endovascular Treatment of Acute Ischemic Stroke Under General Anesthesia:
      Predictors of Good Outcome.
AB  - BACKGROUND: The choice of anesthetic technique, general anesthesia (GA) versus
      Monitored Anesthesia Care, may impact the outcome of patients undergoing
      endovascular treatment of acute ischemic stroke (AIS). The aim of this study was
      to identify the factors associated with good discharge outcome in patients
      receiving GA for AIS. MATERIALS AND METHODS: Electronic medical records of
      patients above 18 years old who underwent endovascular treatment of AIS under GA
      at a Comprehensive Stroke Center from 2010 to 2014 were reviewed. Good outcome
      was defined as discharge modified Rankin Score 0 to 2 and poor outcome as
      modified Rankin Score 3 to 6; logistic regression analysis was performed to
      examine the association between the clinical characteristics and the outcome.
      RESULTS: In total, 88 patients (56 males), aged 63+/-15 years with median
      National Institute of Health Stroke Scale (NIHSS) score 16 (range, 4 to 38) were
      included. Nineteen (22%) patients had good outcome and 78 (88%) had systolic
      blood pressure below the guideline recommended 140 mm Hg under GA. After
      adjusting for age and NIHSS score, the independent predictors of good discharge
      outcomes were higher maximum end-tidal carbon dioxide (odds ratio [OR], 1.14;
      confidence interval [CI], 1.02-1.28; P=0.02) and extubation after endovascular
      treatment (OR, 26.31; CI, 4.80-144.12; P<0.0001). A secondary analysis was
      performed after excluding 25 patients emergently intubated in the Emergency
      Department for airway protection. In the logistic regression analysis controlling
      for age and NIHSS score, postprocedure extubation was still associated with
      higher odds of good outcomes (OR, 13.35; CI, 2.58-68.90; P=0.002). CONCLUSIONS:
      These findings indicate the importance of ventilation management and extubation
      after endovascular intervention under GA in patients with AIS.

PMID- 28763433
TI  - Injury and Liability Associated With Spine Surgery.
AB  - BACKGROUND: Although spine surgery is associated with significant morbidity, the
      anesthesia liability profile for spine surgery is not known. We examined claims
      for spine procedures in the Anesthesia Closed Claims Project database to evaluate
      patterns of injury and liability. MATERIALS AND METHODS: A retrospective cohort
      study was performed. Inclusion criteria were anesthesia claims provided for
      surgical procedures in 2000 to 2014. We compared mechanisms of injury for
      cervical spine to thoracic or lumbar spine procedures using chi and the Fisher
      exact test. Univariate and multivariate logistic regression analyses were used to
      determine factors associated with permanent disabling injury in spine surgery
      claims. RESULTS: The 207 spine procedure (73% thoracic/lumbar; 27% cervical)
      claims comprised >10% of claims. Permanent disabling injuries to nerves, the
      spinal cord, and the eyes or visual pathways were more common with spine
      procedures than in nonspine procedures. Hemorrhage and positioning injuries were
      more common in thoracic/lumbar spine claims, whereas difficult intubation was
      more common in cervical spine claims. Multiple logistic regression demonstrated
      prone positioning (odds ratio=3.50; 95% confidence interval, 1.30-9.43) and
      surgical duration of >=4 hours increased the odds of severe permanent injury in
      spine claims (odds ratio=2.73; 95% confidence interval, 1.11-6.72). CONCLUSIONS:
      Anesthesia claims related to spine surgery were associated with severe permanent
      disability primarily from nerve and eye injuries. Prone positioning and surgical
      duration of >=4 hours were associated with permanent disabling injuries.
      Attention to positioning, resuscitation during blood loss, and reducing length of
      surgery may reduce these complications.

PMID- 28763434
TI  - Comparison of 3% Hypertonic Saline and 20% Mannitol for Reducing Intracranial
      Pressure in Patients Undergoing Supratentorial Brain Tumor Surgery: A Randomized,
      Double-blind Clinical Trial.
AB  - BACKGROUND: In the present study, we hypothesized that 3% hypertonic saline (HS)
      is more effective than 20% mannitol to reduce intracranial pressure (ICP) and to
      modify brain bulk in patients undergoing an elective supratentorial craniotomy.
      MATERIALS AND METHODS: After institutional review board approval, patients
      scheduled to undergo supratentorial craniotomy were enrolled into this
      prospective, randomized, double-blind study. The patients were monitored for
      routine hemodynamic parameters, depth of anesthesia, and ICP. They received 5
      mL/kg 20% mannitol (n=20) or 3% HS (n=19) as infusion for 15 minutes. The
      patients' ICP values were monitored during hypertonic fluid infusion and
      throughout 30 minutes after infusion as a primary outcome. Secondary outcomes
      were hemodynamic variables, serum sodium value, blood gases, and surgeon brain
      relaxation assessment score (1=relaxed, 2=satisfactory, 3=firm, 4=bulging). In
      addition, the length of intensive care unit and hospital stay were recorded.
      RESULTS: Demographic and tumor characteristics were similar between groups. The
      basal (before hypertonic infusion, ICPT0) and last (30 min after hypertonic
      infusion finished, ICPT45) ICP values were 13.7+/-3.0 and 9.5+/-1.9 mm Hg,
      respectively, for the M group, which were comparable with the corresponding
      levels of 14.2+/-2.8 and 8.7+/-1.1 mm Hg in the HS group (P>0.05). The median
      amount of ICP reduction between T0 and T45 timepoints were 4 (1 to 7) and 5 (1 to
      9) mm Hg for group M and group HS, respectively (P=0.035). Baseline central
      venous pressure, pulse pressure variation, and serum sodium and lactate values
      were similar between groups, but the last measured pulse pressure variation and
      lactate value were lower, and sodium value was higher in group HS than in group M
      (P<0.05). Duration of hospital and intensive care unit stay were similar between
      groups. CONCLUSIONS: Our results suggest that 3% HS provided more effective ICP
      reduction than 20% mannitol during supratentorial brain tumor surgery.

PMID- 28763435
TI  - Therapeutic Effect of Sodium Glucose Co-Transporter 2 Inhibitor Dapagliflozin on
      Renal Cell Carcinoma.
AB  - BACKGROUND Patients with type 2 diabetes mellitus (T2DM) have a high incidence of
      renal cell carcinoma (RCC) and high sodium glucose co-transporters 2 (SGLT2)
      expressions. The purpose of this study was to evaluate the anticancer activity of
      dapagliflozin as an SGLT2 inhibitor on RCC cell lines in vitro and in vivo.
      MATERIAL AND METHODS qRT-PCR and Western blot were used to detect SGLT2
      expression on different human renal cells. Then, flow cytometry and
      immunofluorescence were used to investigate the effects of dapagliflozin on cell
      cycle, apoptosis, and SGLT2 expression of CaKi-1 cells. Finally, a xenograft
      model and immunohistochemical staining were used to investigate the function of
      dapagliflozin in nude mice. RESULTS We proved that SGLT2 is highly expressed in
      RCC cell lines. We found that dapagliflozin exerts a higher cytotoxic effect on
      human RCC than on normal human renal cells, regulates the cell cycle and
      apoptosis, and reduces the glucose uptake and SGLT2 expression of CaKi-1 cells.
      Moreover, dapagliflozin inhibits tumor growth and reduces SGLT2 expression in
      vivo. CONCLUSIONS Our results indicate that dapagliflozin has high efficiency and
      low toxicity and could be a new therapeutic target for RCC.

PMID- 28763436
TI  - The beneficial effects of dietary restriction on learning are distinct from its
      effects on longevity and mediated by depletion of a neuroinhibitory metabolite.
AB  - In species ranging from humans to Caenorhabditis elegans, dietary restriction
      (DR) grants numerous benefits, including enhanced learning. The precise
      mechanisms by which DR engenders benefits on processes related to learning remain
      poorly understood. As a result, it is unclear whether the learning benefits of DR
      are due to myriad improvements in mechanisms that collectively confer improved
      cellular health and extension of organismal lifespan or due to specific neural
      mechanisms. Using an associative learning paradigm in C. elegans, we investigated
      the effects of DR as well as manipulations of insulin, mechanistic target of
      rapamycin (mTOR), AMP-activated protein kinase (AMPK), and autophagy pathways
      processes implicated in longevity-on learning. Despite their effects on a vast
      number of molecular effectors, we found that the beneficial effects on learning
      elicited by each of these manipulations are fully dependent on depletion of
      kynurenic acid (KYNA), a neuroinhibitory metabolite. KYNA depletion then leads,
      in an N-methyl D-aspartate receptor (NMDAR)-dependent manner, to activation of a
      specific pair of interneurons with a critical role in learning. Thus,
      fluctuations in KYNA levels emerge as a previously unidentified molecular
      mechanism linking longevity and metabolic pathways to neural mechanisms of
      learning. Importantly, KYNA levels did not alter lifespan in any of the
      conditions tested. As such, the beneficial effects of DR on learning can be
      attributed to changes in a nutritionally sensitive metabolite with
      neuromodulatory activity rather than indirect or secondary consequences of
      improved health and extended longevity.

PMID- 28763437
TI  - Variation of the meiotic recombination landscape and properties over a broad
      evolutionary distance in yeasts.
AB  - Meiotic recombination is a major factor of genome evolution, deeply characterized
      in only a few model species, notably the yeast Saccharomyces cerevisiae.
      Consequently, little is known about variations of its properties across species.
      In this respect, we explored the recombination landscape of Lachancea kluyveri, a
      protoploid yeast species that diverged from the Saccharomyces genus more than 100
      million years ago and we found striking differences with S. cerevisiae. These
      variations include a lower recombination rate, a higher frequency of chromosomes
      segregating without any crossover and the absence of recombination on the
      chromosome arm containing the sex locus. In addition, although well conserved
      within the Saccharomyces clade, the S. cerevisiae recombination hotspots are not
      conserved over a broader evolutionary distance. Finally and strikingly, we found
      evidence of frequent reversal of commitment to meiosis, resulting in return to
      mitotic growth after allele shuffling. Identification of this major but
      underestimated evolutionary phenomenon illustrates the relevance of exploring non
      model species.

PMID- 28763438
TI  - Dynamic transcriptome changes during adipose tissue energy expenditure reveal
      critical roles for long noncoding RNA regulators.
AB  - Enhancing brown fat activity and promoting white fat browning are attractive
      therapeutic strategies for treating obesity and associated metabolic disorders.
      To provide a comprehensive picture of the gene regulatory network in these
      processes, we conducted a series of transcriptome studies by RNA sequencing (RNA
      seq) and quantified the mRNA and long noncoding RNA (lncRNA) changes during white
      fat browning (chronic cold exposure, beta-adrenergic agonist treatment, and
      intense exercise) and brown fat activation or inactivation (acute cold exposure
      or thermoneutrality, respectively). mRNA-lncRNA coexpression networks revealed
      dynamically regulated lncRNAs to be largely embedded in nutrient and energy
      metabolism pathways. We identified a brown adipose tissue-enriched lncRNA,
      lncBATE10, that was governed by the cAMP-cAMP response element-binding protein
      (Creb) axis and required for a full brown fat differentiation and white fat
      browning program. Mechanistically, lncBATE10 can decoy Celf1 from Pgc1alpha,
      thereby protecting Pgc1alpha mRNA from repression by Celf1. Together, these
      studies provide a comprehensive data framework to interrogate the transcriptomic
      changes accompanying energy homeostasis transition in adipose tissue.

PMID- 28763439
TI  - Rearrangement moves on rooted phylogenetic networks.
AB  - Phylogenetic tree reconstruction is usually done by local search heuristics that
      explore the space of the possible tree topologies via simple rearrangements of
      their structure. Tree rearrangement heuristics have been used in combination with
      practically all optimization criteria in use, from maximum likelihood and
      parsimony to distance-based principles, and in a Bayesian context. Their basic
      components are rearrangement moves that specify all possible ways of generating
      alternative phylogenies from a given one, and whose fundamental property is to be
      able to transform, by repeated application, any phylogeny into any other
      phylogeny. Despite their long tradition in tree-based phylogenetics, very little
      research has gone into studying similar rearrangement operations for phylogenetic
      network-that is, phylogenies explicitly representing scenarios that include
      reticulate events such as hybridization, horizontal gene transfer, population
      admixture, and recombination. To fill this gap, we propose "horizontal" moves
      that ensure that every network of a certain complexity can be reached from any
      other network of the same complexity, and "vertical" moves that ensure
      reachability between networks of different complexities. When applied to
      phylogenetic trees, our horizontal moves-named rNNI and rSPR-reduce to the best
      known moves on rooted phylogenetic trees, nearest-neighbor interchange and rooted
      subtree pruning and regrafting. Besides a number of reachability results
      separating the contributions of horizontal and vertical moves-we prove that rNNI
      moves are local versions of rSPR moves, and provide bounds on the sizes of the
      rNNI neighborhoods. The paper focuses on the most biologically meaningful
      versions of phylogenetic networks, where edges are oriented and reticulation
      events clearly identified. Moreover, our rearrangement moves are robust to the
      fact that networks with higher complexity usually allow a better fit with the
      data. Our goal is to provide a solid basis for practical phylogenetic network
      reconstruction.

PMID- 28763440
TI  - Developing international open science collaborations: Funder reflections on the
      Open Science Prize.
AB  - The Open Science Prize was established with the following objectives: first, to
      encourage the crowdsourcing of open data to make breakthroughs that are of
      biomedical significance; second, to illustrate that funders can indeed work
      together when scientific interests are aligned; and finally, to encourage
      international collaboration between investigators with the intent of achieving
      important innovations that would not be possible otherwise. The process for
      running the competition and the successes and challenges that arose are
      presented.

PMID- 28763441
TI  - Correction: Human mutations in integrator complex subunits link transcriptome
      integrity to brain development.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1006809.].

PMID- 28763442
TI  - Counting stillbirths and achieving accountability: A global health priority.
AB  - In a Perspective, Zulfiqar Bhutta discusses the importance of regular and timely
      reporting on stillbirths.

PMID- 28763443
TI  - Intermittent hypoxic training improves anaerobic performance in competitive
      swimmers when implemented into a direct competition mesocycle.
AB  - The main objective of this research was to evaluate the efficacy of intermittent
      hypoxic training (IHT) on anaerobic and aerobic capacity and swimming performance
      in well-trained swimmers. Sixteen male swimmers were randomly divided into a
      hypoxia (H) group (n = 8), which trained in a normobaric hypoxia environment, and
      a control (C) group (n = 8), which exercised under normoxic conditions. However,
      one participant left the study without explanation. During the experiment group H
      trained on land twice per week in simulated hypoxia (FiO2 = 15.5%, corresponding
      to 2,500 m a.s.l); however, they conducted swim training in normoxic conditions.
      Group C performed the same training program under normoxic conditions. The
      training program included four weekly microcyles, followed by three days of
      recovery. During practice sessions on land, the swimmers performed 30 second
      sprints on an arm-ergometer, alternating with two minute high intensity intervals
      on a lower limb cycle ergometer. The results showed that the training on land
      caused a significant (p<0.05) increase in absolute maximal workload (WRmax) by
      7.4% in group H and by 3.2% in group C and relative values of VO2max by 6.9% in
      group H and 3.7% in group C. However, absolute values of VO2max were not
      significantly changed. Additionally, a significant (p<0.05) increase in mean
      power (Pmean) during the first (11.7%) and second (11.9%) Wingate tests was only
      observed in group H. The delta values of lactate concentration (DeltaLA) after
      both Wingate tests were significantly (p<0.05) higher in comparison to baseline
      levels by 28.8% in group H. Opposite changes were observed in delta values of
      blood pH (DeltapH) after both Wingate tests in group H, with a significant
      decrease in values of DeltapH by 33.3%. The IHT caused a significant (p<0.05)
      improvement in 100m and 200m swimming performance, by 2.1% and 1.8%, respectively
      in group H. Training in normoxia (group C), resulted in a significant (p<0.05)
      improvement of swimming performance at 100m and 200m, by 1.1% and 0.8%,
      respectively. In conclusion, the most important finding of this study includes a
      significant improvement in anaerobic capacity and swimming performance after high
      intensity IHT. However, this training protocol had no effect on absolute values
      of VO2max and hematological variables.

PMID- 28763444
TI  - Childhood adiposity and risk of type 1 diabetes: A Mendelian randomization study.
AB  - BACKGROUND: The incidence of type 1 diabetes (T1D) is increasing globally. One
      hypothesis is that increasing childhood obesity rates may explain part of this
      increase, but, as T1D is rare, intervention studies are challenging to perform.
      The aim of this study was to assess this hypothesis with a Mendelian
      randomization approach that uses genetic variants as instrumental variables to
      test for causal associations. METHODS AND FINDINGS: We created a genetic
      instrument of 23 single nucleotide polymorphisms (SNPs) associated with childhood
      adiposity in children aged 2-10 years. Summary-level association results for
      these 23 SNPs with childhood-onset (<17 years) T1D were extracted from a meta
      analysis of genome-wide association study with 5,913 T1D cases and 8,828
      reference samples. Using inverse-variance weighted Mendelian randomization
      analysis, we found support for an effect of childhood adiposity on T1D risk (odds
      ratio 1.32, 95% CI 1.06-1.64 per standard deviation score in body mass index [SDS
      BMI]). A sensitivity analysis provided evidence of horizontal pleiotropy bias (p
      = 0.04) diluting the estimates towards the null. We therefore applied Egger
      regression and multivariable Mendelian randomization methods to control for this
      type of bias and found evidence in support of a role of childhood adiposity in
      T1D (odds ratio in Egger regression, 2.76, 95% CI 1.40-5.44). Limitations of our
      study include that underlying genes and their mechanisms for most of the genetic
      variants included in the score are not known. Mendelian randomization requires
      large sample sizes, and power was limited to provide precise estimates. This
      research has been conducted using data from the Early Growth Genetics (EGG)
      Consortium, the Genetic Investigation of Anthropometric Traits (GIANT)
      Consortium, the Tobacco and Genetics (TAG) Consortium, and the Social Science
      Genetic Association Consortium (SSGAC), as well as meta-analysis results from a
      T1D genome-wide association study. CONCLUSIONS: This study provides genetic
      support for a link between childhood adiposity and T1D risk. Together with
      evidence from observational studies, our findings further emphasize the
      importance of measures to reduce the global epidemic of childhood obesity and
      encourage mechanistic studies.

PMID- 28763445
TI  - Communicating with people living with dementia who are nonverbal: The creation of
      Adaptive Interaction.
AB  - Loss of verbal language production makes people with dementia appear unreachable.
      We previously presented a case study applying nonverbal communication techniques
      with a lady with dementia who could no longer speak, which we termed Adaptive
      Interaction. The current small-n study examines the applicability of Adaptive
      Interaction as a general tool for uncovering the communication repertoires of non
      verbal individuals living with dementia. Communicative responses of 30
      interaction sessions were coded and analysed in two conditions: Standard
      (Baseline) and Adaptive Interaction (Intervention). All participants retained the
      ability to interact plus a unique communication repertoire comprising a variety
      of nonverbal components, spanning eye gaze, emotion expression, and movement. In
      comparison to Baseline sessions, Intervention sessions were characterised by more
      smiling, looking at ME and imitation behaviour from the people with dementia.
      These findings allude to the potential of Adaptive Interaction as the basis for
      interacting with people living with dementia who can no longer speak.

PMID- 28763446
TI  - Gestational diabetes mellitus and interpregnancy weight change: A population
      based cohort study.
AB  - BACKGROUND: Being overweight is an important risk factor for Gestational Diabetes
      Mellitus (GDM), but the underlying mechanisms are not understood. Weight change
      between pregnancies has been suggested to be an independent mechanism behind GDM.
      We assessed the risk for GDM in second pregnancy by change in Body Mass Index
      (BMI) from first to second pregnancy and whether BMI and gestational weight gain
      modified the risk. METHODS AND FINDINGS: In this observational cohort, we
      included 24,198 mothers and their 2 first pregnancies in data from the Medical
      Birth Registry of Norway (2006-2014). Weight change, defined as prepregnant BMI
      in second pregnancy minus prepregnant BMI in first pregnancy, was divided into 6
      categories by units BMI (kilo/square meter). Relative risk (RR) estimates were
      obtained by general linear models for the binary family and adjusted for maternal
      age at second delivery, country of birth, education, smoking in pregnancy,
      interpregnancy interval, and year of second birth. Analyses were stratified by
      BMI (first pregnancy) and gestational weight gain (second pregnancy). Compared to
      women with stable BMI (-1 to 1), women who gained weight between pregnancies had
      higher risk of GDM-gaining 1 to 2 units: adjusted RR 2.0 (95% CI 1.5 to 2.7), 2
      to 4 units: RR 2.6 (2.0 to 3.5), and >=4 units: RR 5.4 (4.0 to 7.4). Risk
      increased significantly both for women with BMI below and above 25 at first
      pregnancy, although it increased more for the former group. A limitation in our
      study was the limited data on BMI in 2 pregnancies. CONCLUSIONS: The risk of GDM
      increased with increasing weight gain from first to second pregnancy, and more
      strongly among women with BMI < 25 in first pregnancy. Our results suggest weight
      change as a metabolic mechanism behind the increased risk of GDM, thus weight
      change should be acknowledged as an independent factor for screening GDM in
      clinical guidelines. Promoting healthy weight from preconception through the
      postpartum period should be a target.

PMID- 28763447
TI  - BRAPH: A graph theory software for the analysis of brain connectivity.
AB  - The brain is a large-scale complex network whose workings rely on the interaction
      between its various regions. In the past few years, the organization of the human
      brain network has been studied extensively using concepts from graph theory,
      where the brain is represented as a set of nodes connected by edges. This
      representation of the brain as a connectome can be used to assess important
      measures that reflect its topological architecture. We have developed a freeware
      MatLab-based software (BRAPH-BRain Analysis using graPH theory) for connectivity
      analysis of brain networks derived from structural magnetic resonance imaging
      (MRI), functional MRI (fMRI), positron emission tomography (PET) and
      electroencephalogram (EEG) data. BRAPH allows building connectivity matrices,
      calculating global and local network measures, performing non-parametric
      permutations for group comparisons, assessing the modules in the network, and
      comparing the results to random networks. By contrast to other toolboxes, it
      allows performing longitudinal comparisons of the same patients across different
      points in time. Furthermore, even though a user-friendly interface is provided,
      the architecture of the program is modular (object-oriented) so that it can be
      easily expanded and customized. To demonstrate the abilities of BRAPH, we
      performed structural and functional graph theory analyses in two separate
      studies. In the first study, using MRI data, we assessed the differences in
      global and nodal network topology in healthy controls, patients with amnestic
      mild cognitive impairment, and patients with Alzheimer's disease. In the second
      study, using resting-state fMRI data, we compared healthy controls and
      Parkinson's patients with mild cognitive impairment.

PMID- 28763448
TI  - Frequency sensitive mechanism in low-intensity ultrasound enhanced bioeffects.
AB  - This study presents two novel theoretical models to elucidate frequency sensitive
      nuclear mechanisms in low-intensity ultrasound enhanced bioeffects. In contrast
      to the typical 1.5 MHz pulsed ultrasound regime, our group previously
      experimentally confirmed that ultrasound stimulation of anchored chondrocytes at
      resonant frequency maximized gene expression of load inducible genes which are
      regulatory markers for cellular response to external stimuli. However, ERK
      phosphorylation displayed no frequency dependency, suggesting that the
      biochemical mechanisms involved in enhanced gene expression is downstream of ERK
      phosphorylation. To elucidate such underlying mechanisms, this study presents a
      theoretical model of an anchored cell, representing an in vitro chondrocyte, in
      an ultrasound field. The model results showed that the mechanical energy storage
      is maximized at the chondrocyte's resonant frequency and the energy density in
      the nucleus is almost twice as high as in the cytoplasm. Next, a mechanochemical
      model was developed to link the mechanical stimulation of ultrasound and the
      increased mechanical energy density in the nucleus to the downstream targets of
      the ERK pathway. This study showed for the first time that ultrasound stimulation
      induces frequency dependent gene expression as a result of altered rates of
      transcription factors binding to chromatin.

PMID- 28763449
TI  - Identification of factors associated with stillbirth in the Indian state of Bihar
      using verbal autopsy: A population-based study.
AB  - BACKGROUND: India was estimated to have the largest numbers of stillbirths
      globally in 2015, and the Indian government has adopted a target of <10
      stillbirths per 1,000 births by 2030 through the India Newborn Action Plan
      (INAP). The objective of this study was to use verbal autopsy interviews to
      examine factors associated with stillbirth in the Indian state of Bihar and make
      recommendations for the INAP to better inform the setting of priorities and
      actions to reduce stillbirths. METHODS AND FINDINGS: Verbal autopsy interviews
      were conducted for deaths including stillbirths that occurred from January 2011
      to March 2014 in a sample of 109,689 households (87.1% participation) in 1,017
      clusters representative of the state of Bihar. The Population Health Metrics
      Research Consortium shortened verbal autopsy questionnaire was used for each
      interview, and cause of death was assigned using the SmartVA automated algorithm.
      A stillbirth was defined as a foetal death with a gestation period of >=28 weeks
      wherein the foetus did not show any sign of life. We report on the stillbirth
      epidemiology and present case studies from the qualitative data on the health
      provider interface that can be used to improve success of improved, skilled care
      at birth and delivery interventions. The annualised stillbirth incidence was 21.2
      (95% CI 19.7 to 22.6) per 1,000 births, with it being higher in the rural areas.
      A total of 1,132 stillbirths were identified; 686 (62.2%) were boys, 327 (29.7%)
      were firstborn, and 760 (68.9%) were delivered at a health facility. Of all the
      stillbirths, 54.5% were estimated to be antepartum. Only 6,161 (55.9%) of the
      women reported at least 1 antenatal care visit, and 33% of the women reported not
      consuming the iron folic acid tablets during pregnancy. Significant differences
      were seen in delivery-related variables and associated maternal conditions based
      on the place of delivery and type of stillbirth. Only 6.1% of the women reported
      having undergone a test to rule out syphilis. For 34.2% of the stillbirths, the
      possible risk factor for stillbirth was unexplained. For the remaining 65.8% of
      the women who reported at least 1 complication during the last 3 months of
      pregnancy, maternal conditions including anaemia, fever during labour, and
      hypertension accounted for most of the complications. Of importance to note is
      that the maternal conditions overlapped quite significantly with the other
      possible underlying risk factors for stillbirth. Obstetrics complications and
      excessive bleeding during delivery contributed to nearly 30% of the cases as a
      possible risk factor for stillbirth, highlighting the need for better skilled
      care during delivery. Of the 5 major themes identified in open narratives, 3 were
      related to healthcare providers-lack of timely attention, poor skills (knowledge
      or implementation), and reluctance to deliver a dead baby. The case studies
      document the circumstances that highlight breakdowns in clinical care around the
      delivery or missed opportunities that can be used for improving the provision of
      quality skilled care. The main limitation of these data is that stillbirth is
      defined based on the gestation period and not based on birth weight; however,
      this is done in several studies from developing country settings in which
      birthweight is either not available or accurate. CONCLUSIONS: To our knowledge,
      this study is among the few large, population-based assessments of stillbirths
      using verbal autopsy at the state level in India. These findings provide detailed
      insight into investigating the possible risk factors for stillbirths, as well as
      insight into the ground-level changes that are needed within the health system to
      design and implement effective preventive and intervention policies to reduce the
      burden of stillbirths. As most of the stillbirths are preventable with high
      quality, evidence-based interventions delivered before and during pregnancy and
      during labour and childbirth, it is imperative that with INAP in place, India
      aspires to document stillbirths in a systematic and standardised manner to bridge
      the knowledge gap for appropriate actions to reduce stillbirths. We have made
      several recommendations based on our study that could further strengthen the INAP
      approach to improve the quality and quantity of stillbirth data to avoid this
      needless loss of lives.

PMID- 28763450
TI  - A mathematical model describes the malignant transformation of low grade gliomas:
      Prognostic implications.
AB  - Gliomas are the most frequent type of primary brain tumours. Low grade gliomas
      (LGGs, WHO grade II gliomas) may grow very slowly for the long periods of time,
      however they inevitably cause death due to the phenomenon known as the malignant
      transformation. This refers to the transition of LGGs to more aggressive forms of
      high grade gliomas (HGGs, WHO grade III and IV gliomas). In this paper we propose
      a mathematical model describing the spatio-temporal transition of LGGs into HGGs.
      Our modelling approach is based on two cellular populations with transitions
      between them being driven by the tumour microenvironment transformation occurring
      when the tumour cell density grows beyond a critical level. We show that the
      proposed model describes real patient data well. We discuss the relationship
      between patient prognosis and model parameters. We approximate tumour radius and
      velocity before malignant transformation as well as estimate the onset of this
      process.

PMID- 28763451
TI  - Effectiveness of a stepped-care intervention to prevent major depression in
      patients with type 2 diabetes mellitus and/or coronary heart disease and
      subthreshold depression: A pragmatic cluster randomized controlled trial.
AB  - PURPOSE: Given the public health significance of poorly treatable co-morbid major
      depressive disorders (MDD) among patients with type 2 diabetes mellitus (DM2) and
      coronary heart disease (CHD), we need to investigate whether strategies to
      prevent the development of major depression could reduce its burden of disease.
      We therefore evaluated the effectiveness of a stepped-care program for
      subthreshold depression in comparison with usual care in patients with DM2 and/or
      CHD. METHODS: A cluster randomized controlled trial, with 27 primary care centers
      serving as clusters. A total of 236 DM2 and/or CHD patients with subthreshold
      depression (nine item Patient Health Questionnaire (PHQ-9) score >= 6, no current
      MDD according to DSM-IV criteria) were allocated to the intervention group (N =
      96) or usual care group (n = 140). The stepped-care program was delivered by
      trained practice nurses during one year and consisted of four sequential
      treatment steps: watchful waiting, guided self-help, problem solving treatment
      and referral to the general practitioner. The primary outcome was the 12-month
      cumulative incidence of MDD as measured with the Mini International
      Neuropsychiatric Interview (MINI). Secondary outcomes included severity of
      depression (measured by PHQ-9) at 3, 6, 9 and 12 months. RESULTS: Of 236 patients
      (mean age, 67,5 (SD 10) years; 54.7% men), 210 (89%) completed the MINI at 12
      months. The cumulative incidence of MDD was 9 of 89 (10.1%) participants in the
      intervention group and 12 of 121 (9.9%) participants in the usual care group. We
      found no statistically significant overall effect of the intervention (OR = 1.21;
      95% confidence interval (0.12 to 12.41)) and there were no statistically
      significant differences in the course or severity of depressive symptoms between
      the two groups. CONCLUSIONS: This study suggest that Step-Dep was not more
      effective in preventing MDD than usual care in a primary care population with DM2
      and/or CHD and subthreshold depression.

PMID- 28763452
TI  - Pathogen reduction through additive-free short-wave UV light irradiation retains
      the optimal efficacy of human platelet lysate for the expansion of human bone
      marrow mesenchymal stem cells.
AB  - BACKGROUND: We recently developed and characterized a standardized and clinical
      grade human Platelet Lysate (hPL) that constitutes an advantageous substitute for
      fetal bovine serum (FBS) for human mesenchymal stem cell (hMSC) expansion
      required in cell therapy procedures, avoiding xenogenic risks (virological and
      immunological) and ethical issues. Because of the progressive use of pathogen
      reduced (PR) labile blood components, and the requirement of ensuring the viral
      safety of raw materials for cell therapy products, we evaluated the impact of the
      novel procedure known as THERAFLEX UV-Platelets for pathogen reduction on hPL
      quality (growth factors content) and efficacy (as a medium supplement for hMSC
      expansion). This technology is based on short-wave ultraviolet light (UV-C) that
      induces non-reversible damages in DNA and RNA of pathogens while preserving
      protein structures and functions, and has the main advantage of not needing the
      addition of any photosensitizing additives (that might secondarily interfere with
      hMSCs). METHODOLOGY / PRINCIPAL FINDINGS: We applied the THERAFLEX UV-Platelets
      procedure on fresh platelet concentrates (PCs) suspended in platelet additive
      solution and prepared hPL from these treated PCs. We compared the quality and
      efficacy of PR-hPL with the corresponding non-PR ones. We found no impact on the
      content of five cytokines tested (EGF, bFGF, PDGF-AB, VEGF and IGF-1) but a
      significant decrease in TGF-beta1 (-21%, n = 11, p<0.01). We performed large
      scale culture of hMSCs from bone marrow (BM) during three passages and showed
      that hPL or PR-hPL at 8% triggered comparable BM-hMSC proliferation as FBS at 10%
      plus bFGF. Moreover, after proliferation of hMSCs in an hPL- or PR-hPL-containing
      medium, their profile of membrane marker expression, their clonogenic potential
      and immunosuppressive properties were maintained, in comparison with BM-hMSCs
      cultured under FBS conditions. The potential to differentiate towards the
      adipogenic and osteogenic lineages of hMSCs cultured in parallel in the three
      conditions also remained identical. CONCLUSION / SIGNIFICANCE: We demonstrated
      the feasibility of using UV-C-treated platelets to subsequently obtain pathogen
      reduced hPL, while preserving its optimal quality and efficacy for hMSC expansion
      in cell therapy applications.

PMID- 28763453
TI  - Trophic niches, diversity and community composition of invertebrate top predators
      (Chilopoda) as affected by conversion of tropical lowland rainforest in Sumatra
      (Indonesia).
AB  - Conversion of tropical rainforests into plantations fundamentally alters
      ecological niches of animal species. Generalist predators such as centipedes
      (Chilopoda) may be able to persist in converted ecosystems due to their ability
      to adapt and switch to alternative prey populations. We investigated variations
      in community composition and trophic niches of soil and litter living centipedes
      in a range of ecosystems including rainforests, jungle rubber agroforests, and
      rubber and oil palm monocultures in two landscapes in Sumatra, Indonesia.
      Including information on environmental factors in the soil and litter habitat, we
      explored drivers shaping ecological niches of soil living invertebrate predators
      in one of the world's hotspots of rainforest conversion. Conversion of
      rainforests into agroforests and plantations was associated with a marked change
      in the composition of centipede communities. However, irrespective of major
      differences in habitat characteristics, changes in total abundances were small
      and the overall diversity and biomass of centipedes was similar in each of the
      systems investigated, suggesting that the number of ecological niches for this
      group of predators remains unchanged. By using stable isotope analysis (15N and
      13C), we investigated trophic niche shifts of the centipede community; lower
      delta13C values of centipedes in oil palm plantations as compared to other
      ecosystems suggests that centipedes switch from decomposer prey to other prey,
      presumably understory associated herbivores, due to reduced availability of
      litter associated prey species. The results suggest that the ability to utilize
      alternative prey is a key feature enabling invertebrate predators to persist in
      ecosystems undergoing major structural changes due to anthropogenic land use
      change.

PMID- 28763454
TI  - The introduction of new policies and strategies to reduce inequities and improve
      child health in Kenya: A country case study on progress in child survival, 2000
      2013.
AB  - As of 2015, only 12 countries in the World Health Organization's AFRO region had
      met Millennium Development Goal #4 (MDG#4) to reduce under-five mortality by two
      thirds by 2015. Given the variability across the African region, a four-country
      study was undertaken to examine barriers and facilitators of child survival prior
      to 2015. Kenya was one of the countries selected for an in-depth case study due
      to its insufficient progress in reducing under-five mortality, with only a 28%
      reduction between 1990 and 2013. This paper presents indicators, national
      documents, and qualitative data describing the factors that have both facilitated
      and hindered Kenya's efforts in reducing child mortality. Key barriers identified
      in the data were widespread socioeconomic and geographic inequities in access and
      utilization of maternal, neonatal, and child health (MNCH) care. To reduce these
      inequities, Kenya implemented three major policies/strategies during the study
      period: removal of user fees, the Kenya Essential Package for Health, and the
      Community Health Strategy. This paper uses qualitative data and a policy review
      to explore the early impacts of these efforts. The removal of user fees has been
      unevenly implemented as patients still face hidden expenses. The Kenya Essential
      Package for Health has enabled construction and/or expansion of healthcare
      facilities in many areas, but facilities struggle to provide Emergency Obstetric
      and Neonatal Care (EmONC), neonatal care, and many essential medicines and
      commodities. The Community Health Strategy appears to have had the most impact,
      improving referrals from the community and provision of immunizations, malaria
      prevention, and Prevention of Mother-to-Child Transmission of HIV. However, the
      Community Health Strategy is limited by resources and thus also unevenly
      implemented in many areas. Although insufficient progress was made pre-2015, with
      additional resources and further scale-up of new policies and strategies Kenya
      can make further progress in child survival.

PMID- 28763455
TI  - Identifying relevant biomarkers of brain injury from structural MRI: Validation
      using automated approaches in children with unilateral cerebral palsy.
AB  - Previous studies have proposed that the early elucidation of brain injury from
      structural Magnetic Resonance Images (sMRI) is critical for the clinical
      assessment of children with cerebral palsy (CP). Although distinct aetiologies,
      including cortical maldevelopments, white and grey matter lesions and ventricular
      enlargement, have been categorised, these injuries are commonly only assessed in
      a qualitative fashion. As a result, sMRI remains relatively underexploited for
      clinical assessments, despite its widespread use. In this study, several
      automated and validated techniques to automatically quantify these three classes
      of injury were generated in a large cohort of children (n = 139) aged 5-17,
      including 95 children diagnosed with unilateral CP. Using a feature selection
      approach on a training data set (n = 97) to find severity of injury biomarkers
      predictive of clinical function (motor, cognitive, communicative and visual
      function), cortical shape and regional lesion burden were most often chosen
      associated with clinical function. Validating the best models on the unseen test
      data (n = 42), correlation values ranged between 0.545 and 0.795 (p<0.008),
      indicating significant associations with clinical function. The measured
      prevalence of injury, including ventricular enlargement (70%), white and grey
      matter lesions (55%) and cortical malformations (30%), were similar to the
      prevalence observed in other cohorts of children with unilateral CP. These
      findings support the early characterisation of injury from sMRI into previously
      defined aetiologies as part of standard clinical assessment. Furthermore, the
      strong and significant association between quantifications of injury observed on
      structural MRI and multiple clinical scores accord with empirically established
      structure-function relationships.

PMID- 28763456
TI  - Is directly observed tuberculosis treatment strategy patient-centered? A mixed
      method study in Addis Ababa, Ethiopia.
AB  - INTRODUCTION: The directly observed treatment, short course (DOTS) strategy has
      been considered as an efficacious approach for better tuberculosis (TB) treatment
      adherence and outcome. However, its level of patient centerdness has not been
      studied and documented well. Hence, the study aimed to determine the level of
      patient centeredness' of the DOTS. METHOD: The study used explanatory sequential
      mixed method design in Addis Ababa, Ethiopia. The study employed an interviewer
      administered questionnaire with 601 patients with TB, focus group discussions
      with 23 TB experts, and telephonic-interview with 25 persons lost to follow-up
      from TB treatment. Descriptive and multivariable analyses carried out for the
      quantitative data while thematic analysis was used for the qualitative data.
      RESULT: Forty percent of patients with TB had not received patient-centered TB
      care (PC-TB care) with DOTS. Male gender (AOR = 0.45, 95% CI 0.3, 0.7), good
      communication (AOR = 3.2, 95%CI 1.6, 6.1), and health care providers as a
      treatment supporter (AOR = 3.4, 95% CI 2.1, 5.48) had significant associations
      with PC-TB care. All persons lost to follow-up and TB experts perceived that DOTS
      is merely patient-centered. The identified categories were patient preferences,
      treatment supporter choice, integration of DOTS with nutritional support, mental
      health, and transport services, provider's commitment and communication skills.
      CONCLUSION: DOTS is limited to provide patient-centered TB care. Hence, DOTS
      needs a model that enhances effectiveness towards patient centeredness of TB
      care.

PMID- 28763457
TI  - RORgammat and RORalpha signature genes in human Th17 cells.
AB  - RORgammat and RORalpha are transcription factors of the RAR-related orphan
      nuclear receptor (ROR) family. They are expressed in Th17 cells and have been
      suggested to play a role in Th17 differentiation. Although RORgammat signature
      genes have been characterized in mouse Th17 cells, detailed information on its
      transcriptional control in human Th17 cells is limited and even less is known
      about RORalpha signature genes which have not been reported in either human or
      mouse T cells. In this study, global gene expression of human CD4 T cells
      activated under Th17 skewing conditions was profiled by RNA sequencing. RORgammat
      and RORalpha signature genes were identified in these Th17 cells treated with
      specific siRNAs to knock down RORgammat or RORalpha expression. We have generated
      selective small molecule RORgammat modulators and they were also utilized as
      pharmacological tools in RORgammat signature gene identification. Our results
      showed that RORgammat controlled the expression of a very selective number of
      genes in Th17 cells and most of them were regulated by RORalpha as well albeit a
      weaker influence. Key Th17 genes including IL-17A, IL-17F, IL-23R, CCL20 and CCR6
      were shown to be regulated by both RORgammat and RORalpha. Our results
      demonstrated an overlapping role of RORgammat and RORalpha in human Th17 cell
      differentiation through regulation of a defined common set of Th17 genes.
      RORgammat as a drug target for treatment of Th17 mediated autoimmune diseases
      such as psoriasis has been demonstrated recently in clinical trials. Our results
      suggest that RORalpha could be involved in same disease mechanisms and gene
      signatures identified in this report could be valuable biomarkers for tracking
      the pharmacodynamic effects of compounds that modulate RORgammat or RORalpha
      activities in patients.

PMID- 28763458
TI  - Synthesis of novel coumarin nucleus-based DPA drug-like molecular entity: In
      vitro DNA/Cu(II) binding, DNA cleavage and pro-oxidant mechanism for anticancer
      action.
AB  - Despite substantial research on cancer therapeutics, systemic toxicity and drug
      resistance limits the clinical application of many drugs like cisplatin.
      Therefore, new chemotherapeutic strategies against different malignancies are
      needed. Targeted cancer therapy is a new paradigm for cancer therapeutics which
      targets pathways or chemical entities specific to cancer cells than normal ones.
      Unlike normal cells, cancer cells contain elevated copper which plays an integral
      role in angiogenesis. Copper is an important metal ion associated with chromatin
      DNA, particularly with guanine. Thus, targeting copper via copper-specific
      chelators in cancer cells can serve as an effective anticancer strategy. New
      pharmacophore di(2-picolyl)amine (DPA)-3(bromoacetyl) coumarin (ligand-L) was
      synthesized and characterized by IR, ESI-MS, 1H- and 13C-NMR. Binding ability of
      ligand-L to DNA/Cu(II) was evaluated using a plethora of biophysical techniques
      which revealed ligand-L-DNA and ligand-L-Cu(II) interaction. Competitive
      displacement assay and docking confirmed non-intercalative binding mode of ligand
      L with ctDNA. Cyclic voltammetry confirmed ligand-L causes quasi reversible
      Cu(II)/Cu(I) conversion. Further, acute toxicity studies revealed no toxic
      effects of ligand-L on mice. To evaluate the chemotherapeutic potential and
      anticancer mechanism of ligand-L, DNA damage via pBR322 cleavage assay and
      reactive oxygen species (ROS) generation were studied. Results demonstrate that
      ligand-L causes DNA cleavage involving ROS generation in the presence of Cu(II).
      In conclusion, ligand-L causes redox cycling of Cu(II) to generate ROS which
      leads to oxidative DNA damage and pro-oxidant cancer cell death. These findings
      will establish ligand-L as a lead molecule to synthesize new molecules with
      better copper chelating and pro-oxidant properties against different
      malignancies.

PMID- 28763459
TI  - Metabolic engineering of CHO cells for the development of a robust protein
      production platform.
AB  - Chinese hamster ovary (CHO) cells are the most preferred mammalian host used for
      the bio-pharmaceutical production. A major challenge in metabolic engineering is
      to balance the flux of the tuned heterogonous metabolic pathway and achieve
      efficient metabolic response in a mammalian cellular system. Pyruvate carboxylase
      is an important network element for the cytoplasmic and mitochondrial metabolic
      pathway and efficiently contributes in enhancing the energy metabolism. The
      lactate accumulation in cell culture can be reduced by re-wiring of the pyruvate
      flux in engineered cells. In the present work, we over-expressed the yeast
      cytosolic pyruvate carboxylase (PYC2) enzyme in CHO cells to augment pyruvate
      flux towards the TCA cycle. The dual selection strategy is adopted for the
      screening and isolation of CHO clones containing varying number of PYC2 gene load
      and studied their cellular kinetics. The enhanced PYC2 expression has led to
      enhanced pyruvate flux which, thus, allowed reduced lactate accumulation up to 4
      folds and significant increase in the cell density and culture longevity. With
      this result, engineered cells have shown a significant enhanced antibody
      expression up to 70% with improved product quality (~3 fold) as compared to the
      parental cells. The PYC2 engineering allowed overall improved cell performance
      with various advantages over parent cells in terms of pyruvate, glucose, lactate
      and cellular energy metabolism. This study provides a potential expression
      platform for a bio-therapeutic protein production in a controlled culture
      environment.

PMID- 28763460
TI  - Inhibitory effects and mechanism of dihydroberberine on hERG channels expressed
      in HEK293 cells.
AB  - The human ether-a-go-go-related gene (hERG) potassium channel conducts rapid
      delayed rectifier potassium currents (IKr) and contributes to phase III cardiac
      action potential repolarization. Drugs inhibit hERG channels by binding to
      aromatic residues in hERG helixes. Berberine (BBR) has multiple actions, and its
      hydrogenated derivative dihydroberberine (DHB) is a potential candidate for
      developing new drugs. Previous studies have demonstrated that BBR blocks hERG
      channels and prolongs action potential duration (APD). Our present study aimed to
      investigate the effects and mechanism of DHB on hERG channels. Protein expression
      and the hERG current were analyzed using western blotting and patch-clamp,
      respectively. DHB inhibited the hERG current concentration-dependently after
      instantaneous perfusion, accelerated channel inactivation by directly binding
      tyrosine (Tyr652) and phenylalanine (Phe656), and decreased mature (155-kDa) and
      simultaneously increased immature (135-kDa) hERG expression, respectively. This
      suggests disruption of forward trafficking of hERG channels. Besides, DHB
      remarkably reduced heat shock protein 90 (Hsp90) expression and its interaction
      with hERG, indicating that DHB disrupted hERG trafficking by impairing channel
      folding. Meanwhie, DHB enhanced the expression of cleaved activating
      transcription factor-6 (ATF-6), a biomarker of unfolded protein response (UPR).
      Expression of calnexin and calreticulin, chaperones activated by ATF-6 to
      facilitate channel folding, were also increased, which indicating UPR activation.
      Additionally, the degradation rate of mature 155-kDa hERG increased following DHB
      exposure. In conclusion, we demonstrated that DHB acutely blocked hERG channels
      by binding the aromatic Tyr652 and Phe656. DHB may decrease hERG plasma membrane
      expression through two pathways involving disruption of forward trafficking of
      immature hERG channels and enhanced degradation of mature hERG channels.
      Furthermore, forward trafficking was disrupted by impaired channel folding
      associated with altered interactions between hERG proteins and chaperones.
      Finally, trafficking inhibition activated UPR, and mature hERG channel
      degradation was increased by DHB.

PMID- 28763461
TI  - Effect of ultrasound frequency on the Nakagami statistics of human liver tissues.
AB  - The analysis of the backscattered statistics using the Nakagami parameter is an
      emerging ultrasound technique for assessing hepatic steatosis and fibrosis.
      Previous studies indicated that the echo amplitude distribution of a normal liver
      follows the Rayleigh distribution (the Nakagami parameter m is close to 1).
      However, using different frequencies may change the backscattered statistics of
      normal livers. This study explored the frequency dependence of the backscattered
      statistics in human livers and then discussed the sources of ultrasound
      scattering in the liver. A total of 30 healthy participants were enrolled to
      undergo a standard care ultrasound examination on the liver, which is a natural
      model containing diffuse and coherent scatterers. The liver of each volunteer was
      scanned from the right intercostal view to obtain image raw data at different
      central frequencies ranging from 2 to 3.5 MHz. Phantoms with diffuse scatterers
      only were also made to perform ultrasound scanning using the same protocol for
      comparisons with clinical data. The Nakagami parameter-frequency correlation was
      evaluated using Pearson correlation analysis. The median and interquartile range
      of the Nakagami parameter obtained from livers was 1.00 (0.98-1.05) for 2 MHz,
      0.93 (0.89-0.98) for 2.3 MHz, 0.87 (0.84-0.92) for 2.5 MHz, 0.82 (0.77-0.88) for
      3.3 MHz, and 0.81 (0.76-0.88) for 3.5 MHz. The Nakagami parameter decreased with
      the increasing central frequency (r = -0.67, p < 0.0001). However, the effect of
      ultrasound frequency on the statistical distribution of the backscattered
      envelopes was not found in the phantom results (r = -0.147, p = 0.0727). The
      current results demonstrated that the backscattered statistics of normal livers
      is frequency-dependent. Moreover, the coherent scatterers may be the primary
      factor to dominate the frequency dependence of the backscattered statistics in a
      liver.

PMID- 28763462
TI  - Sativex in resistant multiple sclerosis spasticity: Discontinuation study in a
      large population of Italian patients (SA.FE. study).
AB  - BACKGROUND: The approval of Sativex for the management of multiple sclerosis (MS)
      spasticity opened a new opportunity to many patients. In Italy, the healthcare
      payer can be fully reimbursed by the involved pharma company with the cost of
      treatment for patients not responding after a 4 week (28 days) trial period
      (Payment by Results, PbR), and 50% reimbursed with the cost of 6 weeks (42 days)
      treatment for other patients discontinuing (Cost Sharing, CS). The aim of our
      study was to describe the Sativex discontinuation profile from a large population
      of spasticity treated Italian MS patients. METHODS: We collected data of patients
      from 30 MS centres across the country starting Sativex between January 2014 and
      February 2015. Data were collected from the mandatory Italian Medicines Agency
      (AIFA) web-registry. Predictors of treatment discontinuation were assessed using
      a multivariate Cox proportional regression analysis. RESULTS: During the
      observation period 631 out of 1597 (39.5%) patients discontinued Sativex. The
      Kaplan-Meier estimates curve showed that 333 patients (20.8%) discontinued
      treatment at 4 weeks while 422 patients (26.4%) discontinued at 6 weeks. We found
      after adjusted modeling that a higher NRS score at T1 (adjHR 2.23, 95% 2.07-2.41,
      p<0.001) and a lower baseline NRS score (adjHR 0.51 95% CI 0.46-0.56, p<0.001)
      were predictive of treatment discontinuation. CONCLUSION: These data show that
      the first 6 weeks are useful in identifying those patients in which Sativex could
      be effective, thus avoiding the cost of longer term evaluation.

PMID- 28763463
TI  - Recellularization of a novel off-the-shelf valve following xenogenic implantation
      into the right ventricular outflow tract.
AB  - Current research on valvular heart repair has focused on tissue-engineered heart
      valves (TEHV) because of its potential to grow similarly to native heart valves.
      Decellularized xenografts are a promising solution; however, host
      recellularization remains challenging. In this study, decellularized porcine
      aortic valves were implanted into the right ventricular outflow tract (RVOT) of
      sheep to investigate recellularization potential. Porcine aortic valves,
      decellularized with sodium dodecyl sulfate (SDS), were sterilized by
      supercritical carbon dioxide (scCO2) and implanted into the RVOT of five juvenile
      polypay sheep for 5 months (n = 5). During implantation, functionality of the
      valves was assessed by serial echocardiography, blood tests, and right heart
      pulmonary artery catheterization measurements. The explanted valves were
      characterized through gross examination, mechanical characterization, and
      immunohistochemical analysis including cell viability, phenotype, proliferation,
      and extracellular matrix generation. Gross examination of the valve cusps
      demonstrated the absence of thrombosis. Bacterial and fungal stains were negative
      for pathogenic microbes. Immunohistochemical analysis showed the presence of
      myofibroblast-like cell infiltration with formation of new collagen fibrils and
      the existence of an endothelial layer at the surface of the explant. Analysis of
      cell phenotype and morphology showed no lymphoplasmacytic infiltration. Tensile
      mechanical testing of valve cusps revealed an increase in stiffness while
      strength was maintained during implantation. The increased tensile stiffness
      confirms the recellularization of the cusps by collagen synthesizing cells. The
      current study demonstrated the feasibility of the trans-species implantation of a
      non-fixed decellularized porcine aortic valve into the RVOT of sheep. The
      implantation resulted in recellularization of the valve with sufficient
      hemodynamic function for the 5-month study. Thus, the study supports a potential
      role for use of a TEHV for the treatment of valve disease in humans.

PMID- 28763464
TI  - Efficacy of antibiotherapy for treating flatus incontinence associated with small
      intestinal bacterial overgrowth: A pilot randomized trial.
AB  - AIM: An increase in intestinal gas production due to small intestinal bowel
      overgrowth (SIBO) is a contributing factor for flatus incontinence. The aims of
      our study were to assess the efficacy of metronidazole in a select population of
      patients with flatus incontinence associated with SIBO and to compare its
      efficacy with that of a combination of simethicone and activated charcoal (SC;
      Carbosylane) in randomized experimental arms. METHODS: Adult patients suffering
      from flatus incontinence associated with SIBO diagnosed by a glucose breath test
      were enrolled in the study. They were given metronidazole or Carbosylane (SC) for
      10 days. The reduction in the mean daily number of gas leakages reported in a 3
      day diary before and at the end of the treatment was used as the primary
      endpoint. RESULTS: Of 52 consecutive subjects with flatus incontinence, 23 (44%)
      had SIBO, 16 (33%) of whom were included in and completed the study. The relative
      reduction in flatus incontinence episodes was significantly higher in the
      metronidazole than in the SC group (66.8+/-34.8% vs. 25+/-50%, P = 0.03),
      decreasing by more than 50% in 7 (87.5%) of the subjects in the metronidazole
      group compared with only 1 (12.5%) in the SC group (odds ratio 1.9, 95%
      confidence interval 0.9-56.9, P = 0.06). CONCLUSION: Our results show a promising
      trend indicating that metronidazole might significantly improve flatus
      incontinence associated with SIBO and might be more successful in treating flatus
      incontinence than gas absorbents.

PMID- 28763465
TI  - Antiretroviral resistance following immunological monitoring in a resource
      limited setting of western India: A cross-sectional study.
AB  - BACKGROUND: The free antiretroviral therapy (ART) program in India still relies
      on the clinico-immunological monitoring for diagnosis of treatment failure. As
      the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first
      and second-line regimens, accumulation of drug resistant mutations (DRMs) can
      compromise the efficacy of NRTI. This study was undertaken to describe the
      pattern of HIV DRMs following immunological monitoring and investigate its impact
      on the cycling of NRTI between first- and second-line ART. METHODS AND FINDINGS:
      This cross-sectional study was performed at a state-sponsored ART clinic of Pune
      city in western India between January and June 2016. Consecutive adults receiving
      first-line ART with immunological failure (IF) were recruited for plasma viral
      load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL
      underwent HIV drug resistance genotyping. Of these, 75 plasma sample were
      successfully genotyped. The median CD4 count and duration of ART at the time of
      failure were 98 (IQR: 61.60-153.50) cells/MUL and 4.62 (IQR: 3.17-6.15) years,
      respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor
      resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first
      line failure, sequences from 56.67% of individuals indicated low- to high-level
      resistance to all available NRTI. The proportion of sequences with >=2 thymidine
      analogue mutations (TAMs) and >=3 TAMs were 62.12% and 39.39%, respectively. An
      average of 1.98 TAMs per sequence were observed following IF as compared to 0.37
      TAMs per sequence following targeted PVL monitoring at 12 months of ART from a
      prior study; this difference was significant (p<0.001). CONCLUSION: The option of
      cycling of NRTI analogues between first- and second-line regimens would no longer
      be effective if individuals are followed-up by immunological monitoring due to
      accumulation of mutations. Introduction of routine PVL monitoring is a priority
      for the long-term sustainability of free ART program in India.

PMID- 28763466
TI  - Risk factors for seizure reoccurrence after withdrawal from antiepileptic drugs
      in individuals who have been seizure-free for over 2 years.
AB  - PURPOSE: To observe risk factors for recurrence after withdrawal from
      antiepileptic drugs. METHODS: We assessed 1282 patients with a definite diagnosis
      of epilepsy. RESULTS: In total, 292 patients between 14 and 80 years of age were
      grouped according to risk factors for recurrence. Of these individuals, 119
      discontinued AED(s) and relapsed. The relapse rate was 34.4 per 100 person-years.
      We used a Cox regression for multivariate analysis to investigate the influence
      of the following on seizure recurrence: receiving more than one type of AED (HR =
      2.53, 95% CI 1.24-5.16) and more than 6 months prior to initiation of AED
      treatment (HR 1.47, 95% CI = 1.004-2.15). CONCLUSIONS: Although the decision to
      discontinue AED treatment necessitates an individual evaluation of each patient,
      our study suggests that there may be a high risk of recurrence in individuals
      who: were receiving more than one AEDs and had initiated their AED treatment more
      than 6 months after the initial appearance of epilepsy symptoms.

PMID- 28763467
TI  - Effects of TNF-alpha on penile structure alteration in rats with
      hyperprolactinemia.
AB  - This study aimed to investigate the effects of anti-tumor necrosis factor (TNF)
      alpha antibody (Ab) on alteration of penile structure in the hyperprolactinemia
      (hyperPRL) rat model. HyperPRL was induced in 8-week-old male Sprague-Dawley rats
      by allografting anterior pituitary (AP) glands under the renal capsule (+AP
      rats). Rats implanted with cerebral cortex (CX) were used as sham control (+CX
      rats). At 6 weeks post implantation, rats received either a single intra
      testicular dose of TNF-alpha Ab (12.5 MUg/kg) or testosterone replacement (2
      doses of testosterone enanthate [TE], 3 mg/kg), and they were sacrificed 1 week
      later. Blood and penile tissue was collected for analysis. Compared to +CX rats,
      the +AP group had lower serum testosterone concentration and neuronal nitric
      oxide synthase (nNOS) expression, but exhibited a higher ratio of collagen III/I
      in the corpus cavernosum. Smooth muscle content exhibited no significant changes.
      At 1 week post TNF-alpha Ab injection, the collagen III/I ratio in the +AP group
      was decreased, and the smooth muscle content and nNOS expression increased
      significantly. These findings were comparable to those observed in +AP rats
      receiving TE. Testicular TNF-alpha suppresses testosterone release, which in turn
      results in the erectile dysfunction (ED) seen in hyperPRL. Intra-testicular TNF
      alpha Ab treatment is as effective as testosterone supplementation on penile
      structure normalization in the hyperPRL model.

PMID- 28763468
TI  - Predictors of lung function test severity and outcome in systemic sclerosis
      associated interstitial lung disease.
AB  - Systemic sclerosis-related interstitial lung disease (SSc-ILD) is the leading
      cause of death in SSc. In this study, we aimed to describe the baseline severity
      and evolution of forced vital capacity (FVC) and diffusing capacity for carbon
      monoxide (DLCO) in patients with SSc-ILD and to assess the baseline clinical,
      biological and high-resolution CT scan (HRCT) predictors of this evolution.
      Baseline and serial FVC and DLCO were collected in 75 SSc-ILD patients followed
      during 6.4+/-4.2 years (n = 557 individual data). FVC and DLCO evolution was
      modelled using a linear mixed model with random effect. During follow-up, FVC was
      stable while DLCO significantly decreased (-1.5+/-0.3%/year (p<0.0001). Baseline
      NYHA functional class III/IV, extensive SSc-ILD on HRCT and DLCO<80% were
      associated with a lower baseline FVC. Absence of digital ulcers extensive SSc
      ILD, and FVC<80% and were associated with a lower baseline DLCO. Presence or
      history of digital ulcers and presence of pulmonary hypertension at baseline or
      during follow-up were associated with a faster decline of DLCO overtime. Neither
      age, gender, subtype of SSc nor specificity of autoantibodies were associated
      with baseline severity or outcome of lung function tests. In this SSc-ILD
      population, FVC was therefore stable while DLCO significantly declined over time.
      ILD extension was associated with baseline FVC and DLCO but not with their
      evolution. Presence or history of digital ulcers and pulmonary hypertension were
      predictors of a faster decline of DLCO over time.

PMID- 28763469
TI  - End-of-life care for immigrants in Germany. An epidemiological appraisal of
      Berlin.
AB  - BACKGROUND: Since the late 1950's, a steadily increasing immigrant population in
      Germany is resulting in a subpopulation of aging immigrants. The German health
      care system needs to adjust its services-linguistically, culturally, and
      medically-for this subpopulation of patients. Immigrants make up over 20% of the
      population in Germany, yet the majority receive inadequate medical care. As many
      of the labor immigrants of the 1960s and 1970s are in need of hospice and
      palliative care (HPC), little is known about this specialized care for
      immigrants. This epidemiological study presents utilization of HPC facilities in
      Berlin with a focus on different immigrant groups. METHODS: A validated
      questionnaire was used to collect data from patients at 34 HPC institutions in
      Berlin over 20 months. All newly admitted patients were recruited. Anonymized
      data were coded and analyzed by using SPSS and compared with the population
      statistics of Berlin. RESULTS: 4118 questionnaires were completed and included in
      the analysis. At 11.4% the proportion of immigrants accessing HPC was
      significantly (p<0,001) below their proportion in the general Berlin population.
      This difference was especially seen in the age groups of 51-60 (21.46% immigrants
      in Berlin population, 17.7% immigrants in HPC population) and 61-70 years (16,9%
      vs. 13,1%). The largest ethnic groups are Turks, Russians, and Poles, with a
      different weighting than in the general population: Turkish immigrants were 24%
      of all Berlin immigrants, but only 13.6% of the study immigrant population (OR:
      0.23, 95%CI: 0.18-0.29, p<0.001). Russian and Polish immigrants account for 5.6%
      and 9.2% in the population, but 11.5% and 24.8% in the study population
      respectively (Russian: OR 0.88, 95%CI: 0.66-1.16; Polish: OR 1.17, 95%CI: 0.97
      1.42). Palliative care wards (PC) were used most often (16.7% immigrants of all
      PC patients); outpatient hospice services were used least often by immigrants
      (11.4%). Median age at first admission to HPC was younger in immigrants than non
      immigrants: 61-70 vs. 71-80, p = 0.03. CONCLUSIONS: Immigrants are
      underrepresented in Berlin's HPC and immigrants on average make use of care at a
      younger age than non-immigrants. In this regard, Turkish immigrants in particular
      have the poorest utilization of HPC. These results should prompt research on
      Turkish immigrants, regarding access barriers, since they represent the largest
      immigrant group. This may be due to a lack of cultural sensitivity of the care
      providers and a lack of knowledge about HPC among immigrants. In the comparison
      of the kinds of institutions, immigrants are less likely to access outpatient
      hospice services compared to PC. Apparently, PC appear to be a smaller hurdle for
      utilization. These results show a non-existent, but oft-cited "healthy immigrant
      effect" of the first generation of work immigrants, now entering old age. These
      findings correspond with studies suggesting increased health concerns in
      immigrants. Focused research is needed to promote efforts in providing adequate
      and fair access to HPC for all people in Berlin.

PMID- 28763470
TI  - UNR/CDSE1 expression as prognosis biomarker in resectable pancreatic ductal
      adenocarcinoma patients: A proof-of-concept.
AB  - Pancreatic ductal adenocarcinoma is an aggressive form of pancreatic cancer and
      the fourth leading cause of cancer-related death. When possible, curative
      approaches are based on surgical resection, though not every patient is a
      candidate for surgery. There are clinical guidelines for the management of these
      patients that offer different treatment options depending on the clinical and
      pathologic characteristics. However, the survival rates seen in this kind of
      patients are still low. The CDSE1 gene is located upstream of NRAS and encodes an
      RNA-binding protein termed UNR. The aim of this study was to analyze UNR
      expression and its correlation with outcome in patients with resectable
      pancreatic ductal adenocarcinoma (PDAC). For this, samples from resectable PDAC
      patients who underwent duodenopancreatectomy were used to evaluate UNR protein
      expression by immunohistochemistry using a tissue microarray. Here, we observed
      that low UNR expression was significantly associated with shorter progression
      free survival after surgery (P = 0.010). Moreover, this prognostic marker
      remained significant after Cox proportional hazards model (P = 0.036). We further
      studied the role of CDSE1 expression in patient's prognosis using data from
      public repositories (GEO and TGCA), confirming our results. Interestingly, CDSE1
      expression correlated with that of genes characteristic of an immunogenic
      molecular subtype of pancreatic cancer. Based on these findings, UNR may be
      considered a potential prognostic biomarker for resectable PDAC and may serve to
      guide subsequent adjuvant treatment decisions.

PMID- 28763471
TI  - Modeling perceptions of climatic risk in crop production.
AB  - In agricultural production, land-use decisions are components of economic
      planning that result in the strategic allocation of fields. Climate variability
      represents an uncertainty factor in crop production. Considering yield impact,
      climatic influence is perceived during and evaluated at the end of crop
      production cycles. In practice, this information is then incorporated into
      planning for the upcoming season. This process contributes to attitudes toward
      climate-induced risk in crop production. In the literature, however, the
      subjective valuation of risk is modeled as a risk attitude toward variations in
      (monetary) outcomes. Consequently, climatic influence may be obscured by
      political and market influences so that risk perceptions during the production
      process are neglected. We present a utility concept that allows the inclusion of
      annual risk scores based on mid-season risk perceptions that are incorporated
      into field-planning decisions. This approach is exemplified and implemented for
      winter wheat production in the Kraichgau, a region in Southwest Germany, using
      the integrated bio-economic simulation model FarmActor and empirical data from
      the region. Survey results indicate that a profitability threshold for this crop,
      the level of "still-good yield" (sgy), is 69 dt ha-1 (regional mean Kraichgau
      sample) for a given season. This threshold governs the monitoring process and
      risk estimators. We tested the modeled estimators against simulation results
      using ten projected future weather time series for winter wheat production. The
      mid-season estimators generally proved to be effective. This approach can be used
      to improve the modeling of planning decisions by providing a more comprehensive
      evaluation of field-crop response to climatic changes from an economic risk point
      of view. The methodology further provides economic insight in an
      agrometeorological context where prices for crops or inputs are lacking, but
      farmer attitudes toward risk should still be included in the analysis.

PMID- 28763472
TI  - Infectious bronchitis corona virus establishes productive infection in avian
      macrophages interfering with selected antimicrobial functions.
AB  - Infectious bronchitis virus (IBV) causes respiratory disease leading to loss of
      egg and meat production in chickens. Although it is known that macrophage numbers
      are elevated in the respiratory tract of IBV infected chickens, the role played
      by macrophages in IBV infection, particularly as a target cell for viral
      replication, is unknown. In this study, first, we investigated the ability of IBV
      to establish productive replication in macrophages in lungs and trachea in vivo
      and in macrophage cell cultures in vitro using two pathogenic IBV strains. Using
      a double immunofluorescent technique, we observed that both IBV Massachusetts
      type 41 (M41) and Connecticut A5968 (Conn A5968) strains replicate in avian
      macrophages at a low level in vivo. This in vivo observation was substantiated by
      demonstrating IBV antigens in macrophages following in vitro IBV infection.
      Further, IBV productive infection in macrophages was confirmed by demonstrating
      corona viral particles in macrophages and IBV ribonucleic acid (RNA) in culture
      supernatants. Evaluation of the functions of macrophages following infection of
      macrophages with IBV M41 and Conn A5968 strains revealed that the production of
      antimicrobial molecule, nitric oxide (NO) is inhibited. It was also noted that
      replication of IBV M41 and Conn A5968 strains in macrophages does not interfere
      with the induction of type 1 IFN activity by macrophages. In conclusion, both M41
      and Con A5968 IBV strains infect macrophages in vivo and in vitro resulting
      productive replications. During the replication of IBV in macrophages, their
      ability to produce NO can be affected without affecting the ability to induce
      type 1 IFN activity. Further studies are warranted to uncover the significance of
      macrophage infection of IBV in the pathogenesis of IBV infection in chickens.

PMID- 28763473
TI  - Efficacy and safety of switching from branded to generic antiretrovirals in
      virologically suppressed HIV-infected patients.
AB  - BACKGROUND: Aim of this study was to evaluate the efficacy and the safety of
      switching from branded to generic antiretrovirals in patients with HIV-RNA <50
      copies/mL. METHODS: Matched-cohort study of patients followed at a single
      clinical center. Since September 2014, all patients with HIV-RNA <50 copies/mL
      who were receiving branded lamivudine or zidovudine/lamivudine or efavirenz were
      switched to the generic compound (switchers) and matched, in a ratio 1:1, for age
      (+/-5 years), gender, anti-HCV antibodies, nadir and (+/-50 cells/MUL) baseline
      CD4+ count (+/-100 cells/MUL), duration of antiretroviral therapy (+/-1 year),
      with patients with HIV-RNA <50 copies/mL, on treatment with unavailable generic
      compounds (non-switchers). Incidence rates (IR) of different outcomes were
      calculated and compared by Poisson regression model. A confirmed HIV-RNA >=50
      copies/mL defined virological failure; any change in the antiretroviral regimen
      was defined as treatment discontinuation. RESULTS: Four hundred forty patients
      were switched to generic compounds (268 [61%] on lamivudine, 65 [15%] on
      zidovudine/lamivudine, 87 [20%] on efavirenz and 20 [4%] on efavirenz and either
      lamivudine or zidovudine/lamivudine). Over a median follow-up of 15.0 (12.1-15.7)
      months, virological failure occurred in four switchers (IR: 0.07 [0.02-0.18]/100
      person months of follow-up [PMFU]) and in ten non-switchers (IR: 0.20 [0.10
      0.35]/100-PMFU) (p = 0.0003), while treatment discontinuation occurred in 118
      switchers (IR: 2.05 [1.70-2.44]/100-PMFU) and in 128 non-switchers (IR: 2.37
      [1.99-2.81]/100-PMFU) (p = 0.699). CONCLUSIONS: After more than one year of
      follow-up, we found no evidence of increased risk of reduced efficacy or
      increased toxicity after switching from branded to generic lamivudine or
      zidovudine/lamivudine or efavirenz.

PMID- 28763474
TI  - Effects of individualized electrical impedance tomography and image
      reconstruction settings upon the assessment of regional ventilation distribution:
      Comparison to 4-dimensional computed tomography in a porcine model.
AB  - Electrical impedance tomography (EIT) is a promising imaging technique for
      bedside monitoring of lung function. It is easily applicable, cheap and requires
      no ionizing radiation, but clinical interpretation of EIT-images is still not
      standardized. One of the reasons for this is the ill-posed nature of EIT,
      allowing a range of possible images to be produced-rather than a single explicit
      solution. Thus, to further advance the EIT technology for clinical application,
      thorough examinations of EIT-image reconstruction settings-i.e., mathematical
      parameters and addition of a priori (e.g., anatomical) information-is essential.
      In the present work, regional ventilation distribution profiles derived from
      different EIT finite-element reconstruction models and settings (for GREIT and
      Gauss Newton) were compared to regional aeration profiles assessed by the gold
      standard of 4-dimensional computed tomography (4DCT) by calculating the root mean
      squared error (RMSE). Specifically, non-individualized reconstruction models
      (based on circular and averaged thoracic contours) and individualized
      reconstruction models (based on true thoracic contours) were compared. Our
      results suggest that GREIT with noise figure of 0.15 and non-uniform background
      works best for the assessment of regional ventilation distribution by EIT, as
      verified versus 4DCT. Furthermore, the RMSE of anteroposterior ventilation
      profiles decreased from 2.53+/-0.62% to 1.67+/-0.49% while correlation increased
      from 0.77 to 0.89 after embedding anatomical information into the reconstruction
      models. In conclusion, the present work reveals that anatomically enhanced EIT
      image reconstruction is superior to non-individualized reconstruction models, but
      further investigations in humans, so as to standardize reconstruction settings,
      is warranted.

PMID- 28763475
TI  - The Bos taurus-Bos indicus balance in fertility and milk related genes.
AB  - Numerical approaches to high-density single nucleotide polymorphism (SNP) data
      are often employed independently to address individual questions. We linked
      independent approaches in a bioinformatics pipeline for further insight. The
      pipeline driven by heterozygosity and Hardy-Weinberg equilibrium (HWE) analyses
      was applied to characterize Bos taurus and Bos indicus ancestry. We infer a gene
      co-heterozygosity network that regulates bovine fertility, from data on 18,363
      cattle with genotypes for 729,068 SNP. Hierarchical clustering separated
      populations according to Bos taurus and Bos indicus ancestry. The weights of the
      first principal component were subjected to Normal mixture modelling allowing the
      estimation of a gene's contribution to the Bos taurus-Bos indicus axis. We used
      deviation from HWE, contribution to Bos indicus content and association to
      fertility traits to select 1,284 genes. With this set, we developed a co
      heterozygosity network where the group of genes annotated as fertility-related
      had significantly higher Bos indicus content compared to other functional classes
      of genes, while the group of genes associated with milk production had
      significantly higher Bos taurus content. The network analysis resulted in
      capturing novel gene associations of relevance to bovine domestication events. We
      report transcription factors that are likely to regulate genes associated with
      cattle domestication and tropical adaptation. Our pipeline can be generalized to
      any scenarios where population structure requires scrutiny at the molecular
      level, particularly in the presence of a priori set of genes known to impact a
      phenotype of evolutionary interest such as fertility.

PMID- 28763476
TI  - Climate change-induced water stress suppresses the regeneration of the critically
      endangered forest tree Nyssa yunnanensis.
AB  - Climatic change-induced water stress has been found to threaten the viability of
      trees, especially endangered species, through inhibiting their recruitment. Nyssa
      yunnanensis, a plant species with extremely small populations (PSESP), consists
      of only two small populations of eight mature individuals remaining in
      southwestern China. In order to determine the barriers to regeneration, both in
      situ and laboratory experiments were performed to examine the critical factors
      hindering seed germination and seedling establishment. The results of in situ
      field experiments demonstrated that soil water potentials lower than -5.40 MPa
      (experienced in December) had significantly inhibitory effects on seedling
      survival, and all seedlings perished at a soil water potential of -5.60 MPa
      (January). Laboratory experiments verified that N. yunnanensis seedlings could
      not survive at a 20% PEG 6000 concentration (-5.34 MPa) or 1/5 water-holding
      capacity (WHC; -5.64 MPa), and seed germination was inhibited in the field from
      September (-1.10 MPa) to November (-4.30 MPa). Our results suggested that soil
      water potentials between -5.34 and -5.64 MPa constituted the range of soil water
      potentials in which N. yunnanensis seedlings could not survive. In addition to
      water deficit, intensified autotoxicity, which is concentration-dependent,
      resulted in lower seed germination and seedling survival. Thus, seed
      establishment was probably simultaneously impacted by water deficit and
      aggravated autotoxicity. Meteorological records from the natural distribution
      areas of N. yunnanensis indicated that mean annual rainfall and relative humidity
      have declined by 21.7% and 6.3% respectively over past 55 years, while the
      temperature has increased by 6.0%. Climate change-induced drought, along with a
      poor resistance and adaptability to drought stress, has severely impacted the
      natural regeneration of N. yunnanensis. In conclusion, climate change-induced
      drought has been implicated as a regulating factor in the natural regeneration of
      N. yunnanensis through suppressing seed germination and screening out seedlings
      in the dry season. Based on the experimental findings, habitat restoration and
      microclimate improvement should both be highlighted in the conservation of this
      particular plant species.

PMID- 28763477
TI  - Spatially localized phosphorous metabolism of skeletal muscle in Duchenne
      muscular dystrophy patients: 24-month follow-up.
AB  - OBJECTIVES: To assess the changes in phosphodiester (PDE)-levels, detected by 31P
      magnetic resonance spectroscopy (MRS), over 24-months to determine the potential
      of PDE as marker for muscle tissue changes in Duchenne Muscular Dystrophy (DMD)
      patients. METHODS: Spatially resolved phosphorous datasets were acquired in the
      right lower leg of 18 DMD patients (range: 5-15.4 years) and 12 age-matched
      healthy controls (range: 5-14 years) at three time-points (baseline, 12-months,
      and 24-months) using a 7T MR-System (Philips Achieva). 3-point Dixon images were
      acquired at 3T (Philips Ingenia) to determine muscle fat fraction. Analyses were
      done for six muscles that represent different stages of muscle wasting.
      Differences between groups and time-points were assessed with non-parametric
      tests with correction for multiple comparisons. Coefficient of variance (CV) were
      determined for PDE in four healthy adult volunteers in high and low signal-to
      noise ratio (SNR) datasets. RESULTS: PDE-levels were significantly higher (two
      fold) in DMD patients compared to controls in all analyzed muscles at almost
      every time point and did not change over the study period. Fat fraction was
      significantly elevated in all muscles at all time points compared to healthy
      controls, and increased significantly over time, except in the tibialis posterior
      muscle. The mean within subject CV for PDE-levels was 4.3% in datasets with high
      SNR (>10:1) and 5.7% in datasets with low SNR. DISCUSSION AND CONCLUSION: The
      stable two-fold increase in PDE-levels found in DMD patients in muscles with
      different levels of muscle wasting over 2-year time, including DMD patients as
      young as 5.5 years-old, suggests that PDE-levels may increase very rapidly early
      in the disease process and remain elevated thereafter. The low CV values in high
      and low SNR datasets show that PDE-levels can be accurately and reproducibly
      quantified in all conditions. Our data confirms the great potential of PDE as a
      marker for muscle tissue changes in DMD patients.

PMID- 28763479
TI  - Expression of Merkelcell polyomavirus (MCPyV) large T-antigen in Merkel cell
      carcinoma lymph node metastases predicts poor outcome.
AB  - BACKGROUND: The aim of this study was to determine the prevalence of MCPyV in
      Merkel cell carcinoma (MCC) primaries versus lymph node metastasis and to
      evaluate possible prognostic factors. METHODS: Samples of MCC primaries and lymph
      node metastases were stained immunohistochemically for the MCPyV large T-antigen
      and expression was compared to patients' clinical outcome. RESULTS: 41 MCC
      patients were included. 33 (61%) out of 54 specimens were MCPyV-positive in the
      immunohistochemistry. 15 (47%) out of 32 primary tumors were positive compared to
      18 (82%) out of 22 lymph node metastases. Eleven patients with positive
      polyomavirus expression died from the carcinoma compared to 4 patients without
      virus expression. Cox regression analysis showed worse disease-free survival in
      patients with MCPyV compared to virus-negative lymph nodes (p = 0.002).
      CONCLUSIONS: To our knowledge this is the first study to describe a negative
      prognostic effect of the MCPyV expression in lymph node metastasis in MCC
      patients.

PMID- 28763478
TI  - Individual differences in circadian locomotor parameters correlate with anxiety-
      and depression-like behavior.
AB  - Disrupted circadian rhythms are a core feature of mood and anxiety disorders.
      Circadian rhythms are coordinated by a light-entrainable master clock located in
      the suprachiasmatic nucleus. Animal models of mood and anxiety disorders often
      exhibit blunted rhythms in locomotor activity and clock gene expression.
      Interestingly, the changes in circadian rhythms correlate with mood-related
      behaviours. Although animal models of depression and anxiety exhibit aberrant
      circadian rhythms in physiology and behavior, it is possible that the methodology
      being used to induce the behavioral phenotype (e.g., brain lesions, chronic
      stress, global gene deletion) affect behavior independently of circadian system.
      This study investigates the relationship between individual differences in
      circadian locomotor parameters and mood-related behaviors in healthy rats. The
      circadian phenotype of male Lewis rats was characterized by analyzing wheel
      running behavior under standard 12h:12h LD conditions, constant dark, constant
      light, and rate of re-entrainment to a phase advance. Rats were then tested on a
      battery of behavioral tests: activity box, restricted feeding, elevated plus
      maze, forced swim test, and fear conditioning. Under 12h:12h LD conditions,
      percent of daily activity in the light phase and variability in activity onset
      were associated with longer latency to immobility in the forced swim test.
      Variability in onset also correlated positively with anxiety-like behavior in the
      elevated plus maze. Rate of re-entrainment correlated positively with measures of
      anxiety in the activity box and elevated plus maze. Lastly, we found that free
      running period under constant dark was associated with anxiety-like behaviors in
      the activity box and elevated plus maze. Our results provide a previously
      uncharacterized relationship between circadian locomotor parameters and mood
      related behaviors in healthy rats and provide a basis for future examination into
      circadian clock functioning and mood.

PMID- 28763480
TI  - Effects of irradiance and prey deprivation on growth, cell carbon and
      photosynthetic activity of the freshwater kleptoplastidic dinoflagellate
      Nusuttodinium (= Gymnodinium) aeruginosum (Dinophyceae).
AB  - The freshwater dinoflagellate Nusuttodinium aeruginosum lacks permanent
      chloroplasts. Rather it sequesters chloroplasts as well as other cell organelles,
      like mitochondria and nuclei, from ingested cryptophyte prey. In the present
      study, growth rates, cell production and photosynthesis were measured at seven
      irradiances, ranging from 10 to 140 MUmol photons m-2s-1, when fed the
      cryptophyte Chroomonas sp. Growth rates were positively influenced by irradiance
      and increased from 0.025 d-1 at 10 MUmol photons m-2s-1 to maximum growth rates
      of ~0.3 d-1 at irradiances >= 40 MUmol photons m-2s-1. Similarly, photosynthesis
      ranged from 1.84 to 36.9 pg C cell-1 h-1 at 10 and 140 MUmol photons m-2s-1,
      respectively. The highest rates of photosynthesis in N. aeruginosum only
      corresponded to ~25% of its own cell carbon content and estimated biomass
      production. The measured rates of photosynthesis could not explain the observed
      growth rates at high irradiances. Cultures of N. aeruginosum subjected to prey
      starvation were able to survive for at least 27 days in the light. The
      sequestered chloroplasts maintained their photosynthetic activity during the
      entire period of starvation, during which the population underwent 4 cell
      divisions. This indicates that N. aeruginosum has some control of the
      chloroplasts, which may be able to replicate. In conclusion, N. aeruginosum seems
      to be in an early stage of chloroplast acquisition with some control of its
      ingested chloroplasts.

PMID- 28763481
TI  - Osteoclastic differentiation and resorption is modulated by bioactive metal ions
      Co2+, Cu2+ and Cr3+ incorporated into calcium phosphate bone cements.
AB  - Biologically active metal ions in low doses have the potential to accelerate bone
      defect healing. For successful remodelling the interaction of bone graft
      materials with both bone-forming osteoblasts and bone resorbing osteoclasts is
      crucial. In the present study brushite forming calcium phosphate cements (CPC)
      were doped with Co2+, Cu2+ and Cr3+ and the influence of these materials on
      osteoclast differentiation and activity was examined. Human osteoclasts were
      differentiated from human peripheral blood mononuclear cells (PBMC) both on the
      surface and in indirect contact to the materials on dentin discs. Release of
      calcium, phosphate and bioactive metal ions was determined using ICP-MS both in
      the presence and absence of the cells. While Co2+ and Cu2+ showed a burst
      release, Cr3+ was released steadily at very low concentrations (below 1 MUM) and
      both calcium and phosphate release of the cements was considerably changed in the
      Cr3+ modified samples. Direct cultivation of PBMC/osteoclasts on Co2+ cements
      showed lower attached cell number compared to the reference but high activity of
      osteoclast specific enzymes tartrate resistant acid phosphatase (TRAP), carbonic
      anhydrase II (CAII) and cathepsin K (CTSK) and significantly increased gene
      expression of vitronectin receptor. Indirect cultivation with diluted Co2+ cement
      extracts revealed highest resorbed area compared to all other modifications and
      the reference. Cu2+ cements had cytotoxic effect on PBMC/osteoclasts during
      direct cultivation, while indirect cultivation with diluted extracts from Cu2+
      cements did not provoke cytotoxic effects but a strictly inhibited resorption.
      Cr3+ doped cements did not show cytotoxic effects at all. Gene expression and
      enzyme activity of CTSK was significantly increased in direct culture. Indirect
      cultivation with Cr3+ doped cements revealed significantly higher resorbed area
      compared to the reference. In conclusion Cr3+ doped calcium phosphate cements are
      an innovative cement modification because of their high cytocompatibility and
      support of active resorption by osteoclasts.

PMID- 28763482
TI  - Attention impairments and ADHD symptoms in adult narcoleptic patients with and
      without hypocretin deficiency.
AB  - BACKGROUND: Attentional complaints are common in narcolepsy patients and can
      overlap with daytime sleepiness features. Few studies attempted to characterize
      attentional domains in narcolepsy leading to controversial results. We aimed to
      assess the impact of hypocretin deficiency on attentional functioning by
      comparing performances on the attention network test (ANT) of narcoleptic
      patients with hypocretin deficiency (narcolepsy type 1-NT1) versus patients
      without hypocretin deficiency (narcolepsy type 2-NT2) and healthy controls. We
      also addressed frequency and severity of psychopathological symptoms and their
      influence on performances on ANT. METHODS: Twenty-one NT1 patients, fifteen NT2
      patients and twenty-two healthy controls underwent the ANT, which allows
      assessing three separate attentional processes (alerting, orienting and executive
      control), and a psychometric assessment including questionnaires on attention
      deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, anxiety and
      depression symptoms. RESULTS: NT1 and NT2 patients presented with slower reaction
      times compared to controls. NT1 patients exhibited an impairment of alerting
      network relative to NT2 and healthy controls, while orienting and executive
      control networks efficiency were comparable between groups. NT1 and NT2 displayed
      higher severity of ADHD inattentive domain than controls, NT1 patients also
      displayed higher severity of ADHD hyperactive domain and depressive symptoms. In
      NT1, ADHD and depressive symptoms were positively correlated. CONCLUSIONS:
      Despite a shared slowing of reaction times in both NT1 and NT2, a selective
      impairment of alerting network was present only in hypocretin deficient patients.
      Clinicians should carefully consider attentional deficits and psychopathological
      symptoms, including ADHD symptoms, in the clinical assessment and management of
      patients with narcolepsy.

PMID- 28763483
TI  - Isolation and characterization of a Bacillus amyloliquefaciens strain with
      zearalenone removal ability and its probiotic potential.
AB  - Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by Fusarium
      species, which has been shown to be associated with reproductive disorders in
      livestock, and to a lesser extent with hyperoestrogenic syndromes in humans. The
      aim of this study was to characterize a Bacillus amyloliquefaciens strain with
      ZEN removal ability. A pure culture of a strain designated LN isolated from moldy
      corn samples showed a high ZEN removal capability. Based on microscopic
      observations, biochemical characteristics, and phylogenetic analysis of the 16S
      rRNA gene sequence, LN was identified as B. amyloliquefaciens. After incubation
      of B. amyloliquefaciens LN in Luria-Bertani (LB) medium containing 3.5 ppm of
      ZEN, the ZEN concentration fell below the detection limit within 24 h. In ZEN
      contaminated corn meal medium, B. amyloliquefaciens LN decreased ZEN
      concentration by 92% after 36 h of incubation. In phosphate-buffered saline (PBS)
      containing 5 ppm of ZEN, B. amyloliquefaciens LN reduced the ZEN concentration
      from 5 ppm to 3.28 ppm immediately after coming into contact with ZEN, and
      further reduced the ZEN concentration to 0.36 ppm after 4 h of incubation. The
      amounts of ZEN adsorbed by the cells of B. amyloliquefaciens LN did not increase
      with the extension of incubation time, indicating that B. amyloliquefaciens LN
      not only possessed ZEN adsorption ability, but also exhibited the ability to
      degrade ZEN. In addition, B. amyloliquefaciens LN was non-hemolytic, non
      enterotoxin producing, and displayed probiotic characteristics including acidic
      tolerance, bile salt tolerance, and anti-pathogenic activities. These findings
      suggest that B. amyloliquefaciens LN has a potential to be used as a feed
      additive to reduce the concentrations of ZEN in feedstuffs.

PMID- 28763484
TI  - Evidence for a shape-based recognition of odorants in vivo in the human nose from
      an analysis of the molecular mechanism of lily-of-the-valley odorants detection
      in the Lilial and Bourgeonal family using the C/Si/Ge/Sn switch strategy.
AB  - We performed an analysis of possible mechanisms of ligand recognition in the
      human nose. The analysis is based on in vivo odor threshold determination and in
      vitro Ca2+ imaging assays with a C/Si/Ge/Sn switch strategy applied to the
      compounds Lilial and Bourgeonal, to differentiate between different molecular
      mechanisms of odorant detection. Our results suggest that odorant detection under
      threshold conditions is mainly based on the molecular shape, i.e. the van der
      Waals surface, and electrostatics of the odorants. Furthermore, we show that a
      single olfactory receptor type is responsible for odor detection of Bourgeonal at
      the threshold level in humans in vivo. Carrying out a QM analysis of vibrational
      energies contained in the odorants, there is no evidence for a vibration-based
      recognition.

PMID- 28763485
TI  - Cxcr2 signaling and the microbiome suppress inflammation, bile duct injury, and
      the phenotype of experimental biliary atresia.
AB  - Biliary atresia is progressive fibro-inflammatory cholangiopathy of young
      children. Central to pathogenic mechanisms of injury is the tissue targeting by
      the innate and adaptive immune cells. Among these cells, neutrophils and the IL
      8/Cxcl-8 signaling via its Cxcr2 receptor have been linked to bile duct injury.
      Here, we aimed to investigate whether the intestinal microbiome modulates Cxcr2
      dependent bile duct injury and obstruction. Adult wild-type (WT) and Cxcr2-/-
      mice were fed a diet supplemented with sulfamethoxazole/trimethoprim (SMZ/TMP)
      during pregnancy and lactation, and their pups were injected intraperitoneally
      with rhesus rotavirus (RRV) within 24 hours of life to induce experimental
      biliary atresia. The maternal exposure to SMZ/TMP significantly lowered the
      incidence of jaundice and bile duct obstruction and resulted in improved
      survival, especially in Cxcr2-/- mice. Analyses of the microbiome by deep
      sequencing of 16S rRNA of the neonatal colon showed a delay in bacterial
      colonization of WT mice induced by SMZ/TMP, with a notable switch from
      Proteobacteria to Firmicutes. Interestingly, the genetic inactivation of Cxcr2
      alone produced a similar bacterial shift. When treated with SMZ/TMP, Cxcr2-/-
      mice infected with RRV to induce experimental biliary atresia showed further
      enrichment of Corynebacterium, Anaerococcus and Streptococcus. Among these,
      Anaerococcus lactolyticus was significantly associated with a suppression of
      biliary injury, cholestasis, and survivability. These results suggest that the
      postnatal development of the intestinal microbiota is an important susceptibility
      factor for experimental biliary atresia.

PMID- 28763487
TI  - Nationally representative prevalence estimates of gay, bisexual, and other men
      who have sex with men who have served in the U.S. military.
AB  - OBJECTIVES: To estimate the number of men in the U.S. military who are gay,
      bisexual, or other men who have sex with men (MSM) to inform the development of
      military and other federal policies. STUDY DESIGN: We analyzed data from the
      National Surveys of Family Growth to estimate the number of U.S. men who were
      gay, bisexual, or MSM, and who had served in the military, compared to those who
      did not serve. We stratified using hierarchical categories of gay, bisexual, and
      other MSM to compare proportions in the military and general population. RESULTS:
      We found that 4.23% of men self-reported as gay, bisexual, or other MSM among men
      who served in the military, compared to 4.14% among men who had not served (p =
      0.93). When stratified, we found that 0.78% self-reported as gay among men who
      served in the military, compared to 2.12% among men who had not served (p<0.001).
      CONCLUSIONS: The proportion of men who identified as a gay was lower in the
      military than in the general population. This finding might have been influenced
      by historical military policies related to sexual orientation.

PMID- 28763486
TI  - Comparative analysis of complete plastid genomes from wild soybean (Glycine soja)
      and nine other Glycine species.
AB  - The plastid genomes of different plant species exhibit significant variation,
      thereby providing valuable markers for exploring evolutionary relationships and
      population genetics. Glycine soja (wild soybean) is recognized as the wild
      ancestor of cultivated soybean (G. max), representing a valuable genetic resource
      for soybean breeding programmes. In the present study, the complete plastid
      genome of G. soja was sequenced using Illumina paired-end sequencing and then
      compared it for the first time with previously reported plastid genome sequences
      from nine other Glycine species. The G. soja plastid genome was 152,224 bp in
      length and possessed a typical quadripartite structure, consisting of a pair of
      inverted repeats (IRa/IRb; 25,574 bp) separated by small (178,963 bp) and large
      (83,181 bp) single-copy regions, with a 51-kb inversion in the large single-copy
      region. The genome encoded 134 genes, including 87 protein-coding genes, eight
      ribosomal RNA genes, and 39 transfer RNA genes, and possessed 204 randomly
      distributed microsatellites, including 15 forward, 25 tandem, and 34 palindromic
      repeats. Whole-plastid genome comparisons revealed an overall high degree of
      sequence similarity between G. max and G. gracilis and some divergence in the
      intergenic spacers of other species. Greater numbers of indels and SNP
      substitutions were observed compared with G. cyrtoloba. The sequence of the accD
      gene from G. soja was highly divergent from those of the other species except for
      G. max and G. gracilis. Phylogenomic analyses of the complete plastid genomes and
      76 shared genes yielded an identical topology and indicated that G. soja is
      closely related to G. max and G. gracilis. The complete G. soja genome sequenced
      in the present study is a valuable resource for investigating the population and
      evolutionary genetics of Glycine species and can be used to identify related
      species.

PMID- 28763488
TI  - Anthocyanin rich extract of Brassica oleracea L. alleviates experimentally
      induced myocardial infarction.
AB  - Cardioprotective potential of anthocyanin rich red cabbage extract (ARCE) was
      assessed in H2O2 treated rat neonatal cardiomyoblasts (H9c2 cells) and
      isoproterenol (ISO) induced rodent model of myocardial infarction. H2O2 treated
      H9c2 cells recorded cytotoxicity (48-50%) and apoptosis (57.3%), the same were
      reduced in presence of ARCE (7-10% & 12.3% respectively). Rats pretreated with
      ARCE for 30 days followed by ISO treatment recorded favourable heart: body weight
      ratio as compared to ISO treated group. Also, the mRNA levels of enzymatic
      antioxidants (sod and catalase) and apoptotic genes (bax and bcl-2) in ARCE+ISO
      treated group were similar to the control group suggesting that ARCE pretreatment
      prevents ISO induced depletion of enzymatic antioxidants and apoptosis.
      Histoarchitecture of ventricular tissue of ISO treated group was marked by
      infracted areas (10%) and derangement of myocardium whereas, ARCE+ISO treated
      group (4.5%) recorded results comparable to control (0%). ARCE+ISO treated group
      accounted for upregulation of caveolin-3 and SERCA2a expression as compared to
      the ISO treated group implying towards ARCE mediated reduction in membrane damage
      and calcium imbalance. Molecular docking scores and LigPlot analysis of cyanidin
      3-glucoside (-8.7 Kcal/mol) and delphinidin-3-glucoside (-8.5 Kcal/mol) showed
      stable hydrophobic and electrostatic interactions with beta1 adrenergic receptor.
      Overall this study elucidates the mechanism of ARCE mediated prevention of
      experimentally induced myocardial damage.

PMID- 28763489
TI  - Temporal dynamics of in-situ fiber-adherent bacterial community under ruminal
      acidotic conditions determined by 16S rRNA gene profiling.
AB  - Subacute rumen acidotic (SARA) conditions are a consequence of high grain
      feeding. Recent work has shown that the pattern of grain feeding can
      significantly impact the rumen epimural microbiota. In a continuation of these
      works, the objective of this study was to determine the role of grain feeding
      patterns on the colonization and associated changes in predicted functional
      properties of the fiber-adherent microbial community over a 48 h period. Eight
      rumen-cannulated Holstein cows were randomly assigned to interrupted or
      continuous 60%-grain challenge model (n = 4 per model) to induce SARA conditions.
      Cows in the continuous model were challenged for 4 weeks, whereas cows of
      interrupted model had a 1-wk break in between challenges. To determine dynamics
      of rumen fiber-adherent microbial community we incubated the same hay from the
      diet samples for 24 and 48 h in situ during the baseline (no grain fed), week 1
      and 4 of the continuous grain feeding model as well as during the week 1
      following the break in the interrupted model. Microbial DNA was extracted and
      16SrRNA amplicon (V3-V5 region) sequencing was done with the Illumina MiSeq
      platform. A significant decrease (P < 0.001) in fiber-adherent rumen bacterial
      species richness and diversity was observed at the end of a 4 week continuous
      SARA challenge in comparison to the baseline. A total of 159 operational
      taxonominc units (OTUs) were identified from the microbial population
      representing > 0.1% relative abundance in the rumen, 18 of which were
      significantly impacted by the feeding challenge model. Correlation analysis of
      the significant OTUs to rumen pH as an indicator of SARA showed genus
      Succiniclasticum had a positive correlation to SARA conditions regardless of
      treatment. Predictive analysis of functional microbial properties suggested that
      the glyoxylate/dicarboxylate pathway was increased in response to SARA
      conditions, decreased between 24h to 48h of incubation, negatively correlated
      with propanoate metabolism and positively correlated to members of the
      Veillonellaceae family including Succiniclasticum spp. This may indicate an
      adaptive response in bacterial metabolism under SARA conditions. This research
      clearly indicates that changes to the colonizing fiber-adherent rumen microbial
      population and their predicted functional genes occur in both the short (48 h)
      and long term (4 wk) under both continuous and interrupted SARA challenge models.

PMID- 28763490
TI  - Conformational risk factors of brachycephalic obstructive airway syndrome (BOAS)
      in pugs, French bulldogs, and bulldogs.
AB  - Extremely brachycephalic, or short-muzzled, dog breeds such as pugs, French
      bulldogs, and bulldogs are prone to the conformation-related respiratory disorder
      brachycephalic obstructive airway syndrome (BOAS). Affected dogs present with a
      wide range of clinical signs from snoring and exercise intolerance, to life
      threatening events such as syncope. In this study, conformational risk factors
      for BOAS that could potentially aid in breeding away from BOAS were sought. Six
      hundred and four pugs, French bulldogs, and bulldogs were included in the study.
      Soft tape measurements of the head and body were used and the inter-observer
      reproducibility was evaluated. Breed-specific models were developed to assess the
      associations between the conformational factors and BOAS status based on
      functional grading. The models were further validated by means of a BOAS index,
      which is an objective measurement of respiratory function using whole-body
      barometric plethysmography. The final models have good predictive power for
      discriminating BOAS (-) and BOAS (+) phenotypes indicated by the area under the
      curve values of >80% on the receiver operating curves. When other factors were
      controlled, stenotic nostrils were associated with BOAS in all three breeds; pugs
      and bulldogs with higher body condition scores (BCS) had a higher risk of
      developing BOAS. Among the standardized conformational measurements (i.e.
      craniofacial ratio (CFR), eye width ratio (EWR), skull index (SI), neck girth
      ratio (NGR), and neck length ratio (NLR)), for pugs EWR and SI, for French
      bulldogs NGR and NLR, and for bulldogs SI and NGR showed significant associations
      with BOAS status. However, the NGR in bulldogs was the only significant predictor
      that also had satisfactory inter-observer reproducibility. A NGR higher than 0.71
      in male bulldogs was predictive of BOAS with approximately 70% sensitivity and
      specificity. In conclusion, stenotic nostrils, BCS, and NGR were found to be
      valid, easily applicable predictors for BOAS (+).

PMID- 28763491
TI  - Endoscopic features of lymphoid follicles using blue laser imaging (BLI)
      endoscopy in the colorectum and its association with chronic bowel symptoms.
AB  - BACKGROUND/AIM: In the colorectum, lymphoid follicles hyperplasia (LH) is
      sometimes observed as small, round, yellowish-white nodules. The novel image
      enhanced endoscopy system named blue laser imaging (BLI) provides enhanced the
      contrast of surface vessels using lasers for light illumination. We investigated
      the endoscopic features of LH observed by using BLI endoscopy and its association
      with chronic bowel symptoms. PATIENTS/METHODS: 300 participants undergoing
      colonoscopy for various indications were enrolled. Entire colorectum was observed
      by using BLI-bright mode with non-magnification view. LH was defined as well
      demarcated white nodules. Elevated LH with erythema was distinguished as LH
      severe. RESULTS: LHs were observed more clearly by using BLI-bright mode compared
      to conventional white light colonoscopy and were also histologically confirmed as
      intense infiltration of lymphocytes or plasmacytes. LH was observed in 134
      subjects (44.6%) and 67 (22.3%) were LH severe. LH was associated younger age
      (Odds ratio (OR) = 1.05, 95%Confidence Interval (95%CI) = 1.03-1.07, P<0.0001)
      and chronic bowel symptoms including constipation, hard stools, diarrhea and
      loose stools (all LH: OR = 4.03, 95%CI = 2.36-6.89, P<0.0001, LH severe: OR =
      5.31, 95%CI = 2.64-10.71, P<0.0001). LH severe was closely associated with both
      constipation associated symptoms (OR = 3.94, 95%CI = 1.79-8.66, P = 0.0007) and
      diarrhea associated symptoms (OR = 5.22, 95%CI = 2.09-13.05, P = 0.0004). In
      particular, LH severe in the ascending colon was strongly associated with bowel
      symptoms (P<0.0001). CONCLUSION: LH, visualized by using BLI endoscopy was
      associated with bowel symptom, raising the possibility of pathogenic role of this
      endoscopic finding in the functional lower gastrointestinal disorders.

PMID- 28763492
TI  - Pancreatic atrophy caused by dietary selenium deficiency induces hypoinsulinemic
      hyperglycemia via global down-regulation of selenoprotein encoding genes in
      broilers.
AB  - This study was envisaged to comprehensively profile genes in selected tissues
      along with a few biochemical indicators and integrate resulting information with
      dietary selenium (Se) deficiency symptoms in broilers. A total of 120 one-day-old
      Cobb male broilers were equally divided into two groups and fed a Se deficient
      corn-soybean-based basal diet supplemented with 0.3 mg/kg sodium selenite
      (Control, Se adequate) or without selenite (Se deficiency) for five weeks.
      Effects of Se deficiency on mRNA abundance of twenty-three selenoprotein encoding
      genes and seventeen insulin signaling related genes were studied at day 35 in
      pancreas, liver and muscle along with plasma biochemical constituents and enzyme
      activities. Compared to healthy birds in control diet, Se deficient diet induced
      deficiency symptoms in 90% birds and classic nutritional pancreatic atrophy,
      depressed growth performance of broilers, and decreased (P < 0.01 to P < 0.05)
      total antioxidant capacity and activities of superoxide dismutase and glutathione
      peroxidase in plasma and three other tissues. Se deficiency resulted in 58%
      higher mortality than control birds. Dietary Se deficiency down-regulated (P <
      0.01-0.05) eighteen selenoprotein encoding genes in pancreas, fourteen genes in
      muscle and nine genes in liver, and up-regulated (P < 0.05) Txnrd1 and Selx in
      liver. Meanwhile, six, thirteen and five insulin signaling related genes were
      down-regulated (P < 0.01-0.05) in pancreas, muscle and liver, respectively, and
      three genes were up-regulated (P < 0.01) in liver. The decrease (P < 0.05) in
      levels of plasma insulin, total triglyceride and total cholesterol, and
      concurrent elevated (P < 0.05) levels of plasma glucose and inflammatory
      cytokines accompanied the global down-regulation of selenoprotein encoding- and
      insulin signaling related- genes in Se deficient birds. It was concluded that
      dietary Se deficiency induces nutritional pancreatic atrophy and metabolic
      disorder of glucose and lipid in broilers via down-regulation of selenoprotein
      encoding- and insulin signaling related- genes, indicating potential roles of
      these genes in metabolic regulation.

PMID- 28763493
TI  - Biological evaluation of both enantiomers of fluoro-thalidomide using human
      myeloma cell line H929 and others.
AB  - Over the last few years, thalidomide has become one of the most important anti
      tumour drugs for the treatment of relapsed-refractory multiple myeloma. However,
      besides its undesirable teratogenic side effect, its configurational instability
      critically limits any further therapeutic improvements of this drug. In 1999, we
      developed fluoro-thalidomide which is a bioisostere of thalidomide, but, in sharp
      contrast to the latter, it is configurationally stable and readily available in
      both enantiomeric forms. The biological activity of fluoro-thalidomide however,
      still remains virtually unstudied, with the exception that fluoro-thalidomide is
      not teratogenic. Herein, we report the first biological evaluation of fluoro
      thalidomide in racemic and in both (R)- and (S)-enantiomerically pure forms
      against (in vitro) H929 cells of multiple myeloma (MM) using an annexin V assay.
      We demonstrate that all fluoro-thalidomides inhibited the growth of H929 MM cells
      without any in-vivo activation. Furthermore, we report that the enantiomeric
      forms of fluoro-thalidomide display different anti-tumour activities, with the
      (S)-enantiomer being noticeably more potent. The angiogenesis of fluoro
      thalidomides is also investigated and compared to thalidomide. The data obtained
      in this study paves the way towards novel pharmaceutical research on fluoro
      thalidomides.

PMID- 28763495
TI  - DNA barcoding of odonates from the Upper Plata basin: Database creation and
      genetic diversity estimation.
AB  - We present a DNA barcoding study of Neotropical odonates from the Upper Plata
      basin, Brazil. A total of 38 species were collected in a transition region of
      "Cerrado" and Atlantic Forest, both regarded as biological hotspots, and 130
      cytochrome c oxidase subunit I (COI) barcodes were generated for the collected
      specimens. The distinct gap between intraspecific (0-2%) and interspecific
      variation (15% and above) in COI, and resulting separation of Barcode Index
      Numbers (BIN), allowed for successful identification of specimens in 94% of
      cases. The 6% fail rate was due to a shared BIN between two separate nominal
      species. DNA barcoding, based on COI, thus seems to be a reliable and efficient
      tool for identifying Neotropical odonate specimens down to the species level.
      These results underscore the utility of DNA barcoding to aid specimen
      identification in diverse biological hotspots, areas that require urgent action
      regarding taxonomic surveys and biodiversity conservation.

PMID- 28763494
TI  - Global assessment of small RNAs reveals a non-coding transcript involved in
      biofilm formation and attachment in Acinetobacter baumannii ATCC 17978.
AB  - Many strains of Acinetobacter baumannii have been described as being able to form
      biofilm. Small non-coding RNAs (sRNAs) control gene expression in many regulatory
      circuits in bacteria. The aim of the present work was to provide a global
      description of the sRNAs produced both by planktonic and biofilm-associated
      (sessile) cells of A. baumannii ATCC 17978, and to compare the corresponding gene
      expression profiles to identify sRNAs molecules associated to biofilm formation
      and virulence. sRNA was extracted from both planktonic and sessile cells and
      reverse transcribed. cDNA was subjected to 454-pyrosequencing using the GS-FLX
      Titanium chemistry. The global analysis of the small RNA transcriptome revealed
      different sRNA expression patterns in planktonic and biofilm associated cells,
      with some of the transcripts only expressed or repressed in sessile bacteria. A
      total of 255 sRNAs were detected, with 185 of them differentially expressed in
      the different types of cells. A total of 9 sRNAs were expressed only in biofilm
      cells, while the expression of other 21 coding regions were repressed only in
      biofilm cells. Strikingly, the expression level of the sRNA 13573 was 120 times
      higher in biofilms than in planktonic cells, an observation that prompted us to
      further investigate the biological role of this non-coding transcript. Analyses
      of an isogenic mutant and over-expressing strains revealed that the sRNA 13573
      gene is involved in biofilm formation and attachment to A549 human alveolar
      epithelial cells. The present work serves as a basis for future studies examining
      the complex regulatory network that regulate biofilm biogenesis and attachment to
      eukaryotic cells in A. baumannii ATCC 17978.

PMID- 28763496
TI  - Regional co-location pattern scoping on a street network considering distance
      decay effects of spatial interaction.
AB  - Regional co-location scoping intends to identify local regions where spatial
      features of interest are frequently located together. Most of the previous
      researches in this domain are conducted on a global scale and they assume that
      spatial objects are embedded in a 2-D space, but the movement in urban space is
      actually constrained by the street network. In this paper we refine the scope of
      co-location patterns to 1-D paths consisting of nodes and segments. Furthermore,
      since the relations between spatial events are usually inversely proportional to
      their separation distance, the proposed method introduces the "Distance Decay
      Effects" to improve the result. Specifically, our approach first subdivides the
      street edges into continuous small linear segments. Then a value representing the
      local distribution intensity of events is estimated for each linear segment using
      the distance-decay function. Each kind of geographic feature can lead to a
      tessellated network with density attribute, and the generated multiple networks
      for the pattern of interest will be finally combined into a composite network by
      calculating the co-location prevalence measure values, which are based on the
      density variation between different features. Our experiments verify that the
      proposed approach is effective in urban analysis.

PMID- 28763497
TI  - Diagnosis of coinfection by schistosomiasis and viral hepatitis B or C using 1H
      NMR-based metabonomics.
AB  - BACKGROUND: Diagnosis of liver involvement due to schistosomiasis in asymptomatic
      patients from endemic areas previously diagnosed with chronic hepatitis B (HBV)
      or C (HCV) and periportal fibrosis is challenging. H-1 Nuclear Magnetic Resonance
      (NMR)-based metabonomics strategy is a powerful tool for providing a profile of
      endogenous metabolites of low molecular weight in biofluids in a non-invasive
      way. The aim of this study was to diagnose periportal fibrosis due to
      schistosomiasis mansoni in patients with chronic HBV or HCV infection through NMR
      based metabonomics models. METHODOLOGY/PRINCIPAL FINDINGS: The study included 40
      patients divided into two groups: (i) 18 coinfected patients with schistosomiasis
      mansoni and HBV or HCV; and (ii) 22 HBV or HCV monoinfected patients. The serum
      samples were analyzed through H-1 NMR spectroscopy and the models were based on
      Principal Component Analysis (PCA) and Partial Least Squares-Discriminant
      Analysis (PLS-DA). Ultrasonography examination was used to ascertain the
      diagnosis of periportal fibrosis. Exploratory analysis showed a clear separation
      between coinfected and monoinfected samples. The supervised model built from PLS
      DA showed accuracy, R2 and Q2 values equal to 100%, 98.1% and 97.5%,
      respectively. According to the variable importance in the projection plot,
      lactate serum levels were higher in the coinfected group, while the signals
      attributed to HDL serum cholesterol were more intense in the monoinfected group.
      CONCLUSIONS/SIGNIFICANCE: The metabonomics models constructed in this study are
      promising as an alternative tool for diagnosis of periportal fibrosis by
      schistosomiasis in patients with chronic HBV or HCV infection from endemic areas
      for Schistosoma mansoni.

PMID- 28763498
TI  - Formation flight and collision avoidance for multiple UAVs based on modified
      tentacle algorithm in unstructured environments.
AB  - This paper presents a method for formation flight and collision avoidance of
      multiple UAVs. Due to the shortcomings such as collision avoidance caused by
      UAV's high-speed and unstructured environments, this paper proposes a modified
      tentacle algorithm to ensure the high performance of collision avoidance.
      Different from the conventional tentacle algorithm which uses inverse derivation,
      the modified tentacle algorithm rapidly matches the radius of each tentacle and
      the steering command, ensuring that the data calculation problem in the
      conventional tentacle algorithm is solved. Meanwhile, both the speed sets and
      tentacles in one speed set are reduced and reconstructed so as to be applied to
      multiple UAVs. Instead of path iterative optimization, the paper selects the best
      tentacle to obtain the UAV collision avoidance path quickly. The simulation
      results show that the method presented in the paper effectively enhances the
      performance of flight formation and collision avoidance for multiple high-speed
      UAVs in unstructured environments.

PMID- 28763499
TI  - Risk factors for adverse drug reactions in pediatric inpatients: A cohort study.
AB  - PURPOSE: The present study aims to identify the risk factors for adverse drug
      reactions (ADR) in pediatric inpatients. METHODS: A prospective cohort study in
      one general pediatric ward in a hospital in Northeast Brazil was conducted in two
      stages: the first stage was conducted between August 17th and November 6th, 2015,
      and the second one between March 1st and August 25th, 2016. We included children
      aged 0-14 years 11 months hospitalized with a minimum stay of 48 hours. Observed
      outcomes were the ADR occurrence and the time until the first ADR observed. In
      the univariate analysis, the time to the first ADR was compared among groups
      using a log-rank test. For the multivariate analysis, the Cox regression model
      was used. RESULTS: A total of 173 children (208 admissions) and 66 ADR classified
      as "definite" and "probable" were identified. The incidence rate was 3/100
      patient days. The gastro-intestinal system disorders were the main ADR observed
      (28.8%). In addition, 22.7% of the ADR were related to antibacterials for
      systemic use and 15.2% to general anesthesia. Prior history of ADR of the child
      [hazard ratio (HR) 2.44; 95% confidence interval (CI) 1.19-5.00], the use of
      meglumine antimonate (HR 4.98; 95% CI 1.21-20.54), antibacterial for systemic use
      (HR 2.75; 95% CI 1.08-6.98) and antiepileptic drugs (HR 3.84; 95% CI 1.40-10.56)
      were identified risk factors for ADR. CONCLUSIONS: We identified as risk factors
      the prior history of ADR of the child and the use of meglumine antimonate,
      antibacterial for systemic use and antiepileptic drugs.

PMID- 28763500
TI  - Child contact management in high tuberculosis burden countries: A mixed-methods
      systematic review.
AB  - Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide.
      Considering the World Health Organization recommendation to implement child
      contact management (CCM) for TB, we conducted a mixed-methods systematic review
      to summarize CCM implementation, challenges, predictors, and recommendations. We
      searched the electronic databases of PubMed/MEDLINE, Scopus, and Web of Science
      for studies published between 1996-2017 that reported CCM data from high TB
      burden countries. Protocol details for this systematic review were registered on
      PROSPERO: International prospective register of systematic reviews
      (#CRD42016038105). We formulated a search strategy to identify all available
      studies, published in English that specifically targeted a) population: child
      contacts (<15 years) exposed to TB in the household from programmatic settings in
      high burden countries (HBCs), b) interventions: CCM strategies implemented within
      the CCM cascade, c) comparisons: CCM strategies studied and compared in HBCs, and
      d) outcomes: monitoring and evaluation of CCM outcomes reported in the literature
      for each CCM cascade step. We included any quantitative, qualitative, mixed
      methods study design except for randomized-controlled trials, editorials or
      commentaries. Thirty-seven studies were reviewed. Child contact losses varied
      greatly for screening, isoniazid preventive therapy initiation, and completion.
      CCM challenges included: infrastructure, knowledge, attitudes, stigma, access,
      competing priorities, and treatment. CCM recommendations included: health system
      strengthening, health education, and improved preventive therapy. Identified
      predictors included: index case and clinic characteristics, perceptions of
      barriers and risk, costs, and treatment characteristics. CCM lacks
      standardization resulting in common challenges and losses throughout the CCM
      cascade. Prioritization of a CCM-friendly healthcare environment with improved
      CCM processes and tools; health education; and active, evidence-based strategies
      can decrease barriers. A focused approach toward every aspect of the CCM cascade
      will likely diminish losses throughout the CCM cascade and ultimately decrease TB
      related morbidity and mortality in children.

PMID- 28763501
TI  - Single stranded adeno-associated virus achieves efficient gene transfer to
      anterior segment in the mouse eye.
AB  - Adeno-associated viruses (AAVs) are used extensively as a gene delivery vehicle
      for retinal gene therapy, yet its ability to target the anterior segment of the
      eye, critical to unlocking therapeutic opportunities, is less characterized.
      Previously, self-complimentary (sc) AAV was shown to be necessary for
      transduction of the cornea and trabecular meshwork (TM), limiting the size of the
      gene transfer cassette, likely due to a block in second strand synthesis thought
      to be required for functional transduction. Here, we evaluated several AAV
      capsids in a single stranded (ss) genome conformation for their ability to
      overcome the need for scAAV for targeting corneal endothelium and TM. AAV2, 8,
      and a recently synthetically developed AAV called Anc80L65 were evaluated in
      vitro and in vivo by intracameral injection in mice. Results show that although
      scAAV2 demonstrated superior infectivity in vitro including Human Trabecular
      meshwork (HTM) immortalized cell lines; Anc80L65 transduced following a single
      intracameral injection efficiently all components of the mouse anterior segment,
      including the TM, corneal stroma, and endothelial cells. These results suggest
      that Anc80L65 is able to overcome the requirement for scAAV genomes to enable TM
      and corneal targeting, expanding the potential experimental and therapeutic use
      of AAV gene transfer in the anterior segment of the eye.

PMID- 28763502
TI  - Onset of microglial entry into developing quail retina coincides with increased
      expression of active caspase-3 and is mediated by extracellular ATP and UDP.
AB  - Microglial cell precursors located in the area of the base of the pecten and the
      optic nerve head (BP/ONH) start to enter the retina of quail embryos at the 7th
      day of incubation (E7), subsequently colonizing the entire retina by central-to
      peripheral tangential migration, as previously shown by our group. The present
      study demonstrates a precise chronological coincidence of the onset of microglial
      cell entry into the retina with a striking increase in death of retinal cells, as
      revealed by their active caspase-3 expression and TUNEL staining, in regions
      dorsal to the BP/ONH area, suggesting that dying retinal cells would contribute
      to the microglial cell inflow into the retina. However, the molecular mechanisms
      involved in this inflow are currently unclear. Extracellular nucleotides, such as
      ATP and UDP, have previously been shown to favor migration of microglia towards
      brain injuries because they are released by apoptotic cells and stimulate both
      chemotaxis and chemokinesis in microglial cells via signaling through purinergic
      receptors. Hence, we tested here the hypothesis that ATP and UDP play a role in
      the entry and migration of microglial precursors into the developing retina. For
      this purpose, we used an experimental model system based on organotypic cultures
      of E6.5 quail embryo retina explants, which mimics the entry and migration of
      microglial precursors in the in situ developing retina. Inhibition of purinergic
      signaling by treating retina explants with either apyrase, a nucleotide
      hydrolyzing enzyme, or suramin, a broad spectrum antagonist of purinergic
      receptors, significantly prevents the entry of microglial cells into the retina.
      In addition, treatment of retina explants with either exogenous ATP or UDP
      results in significantly increased numbers of microglial cells entering the
      retina. In light of these findings, we conclude that purinergic signaling by
      extracellular ATP and UDP is necessary for the entry and migration of microglial
      cells into the embryonic retina by inducing chemokinesis in these cells.

PMID- 28763503
TI  - Increased heterogeneity of brain perfusion is an early marker of central nervous
      system involvement in antiphospholipid antibody carriers.
AB  - OBJECTIVE: The non-criteria neuropsychiatric manifestations of antiphospholipid
      syndrome include headache, dizziness, vertigo, seizure, depression and psychosis.
      There were still no objective methods qualified to detect the early central
      nervous system involvement in non-criteria antiphospholipid syndrome. We
      evaluated the effectiveness of Tc-99m ECD SPECT in assessing circulatory
      insufficiency in the brains of patients with antiphospholipid antibodies and
      neuropsychiatric symptoms but without thromboembolism. MATERIALS AND METHODS:
      Patients with a history of positive antiphospholipid antibodies and
      neuropsychiatric symptoms composed the case group; patients without
      antiphospholipid antibody served as the control group. Subjects with a history of
      thromboembolism or autoantibodies to extractable nuclear antigens were excluded.
      All patients received Tc-99m ECD SPECT studies and were classified by the number
      of positive antiphospholipid antibodies they carried. The heterogeneity of brain
      perfusion was defined as the coefficient of variation of the SPECT signals.
      Analysis of variance (ANOVA) was applied to evaluate the differences between the
      groups. RESULTS: Total 60 adult patients were included in this study. There were
      54 patients in the case group and 6 patients in the control group. The mean age
      was 38.3 +/- 11.5 years. There were 52 women and 8 men. There was no significant
      difference in the mean brain perfusion between groups (P = 0.69). However, Tc-99m
      ECD SPECT demonstrated significant heterogeneity of brain perfusion in relation
      to the number of antiphospholipid antibodies (P = 0.01). CONCLUSIONS: This is the
      first study demonstrating that Tc-99m ECD SPECT can early detect the increased
      heterogeneity of brain circulation in non-criteria antiphospholipid antibody
      carriers.

PMID- 28763504
TI  - Full course macro-kinematic analysis of a 10 km classical cross-country skiing
      competition.
AB  - In this study micro-sensors were employed to analyse macro-kinematic parameters
      during a classical cross-country skiing competition (10 km, 2-lap). Data were
      collected from eight male participants during the Australian championship
      competition wearing a single micro-sensor unit (MinimaxXTM, S4) positioned on
      their upper back. Algorithms and visual classification were used to identify
      skiing sub-techniques and calculate velocities, cycle lengths (CL) and cycle
      rates (CR) over the entire course. Double poling (DP) was the predominant
      cyclical sub-technique utilised (43 +/- 5% of total distance), followed by
      diagonal stride (DS, 16 +/- 4%) and kick double poling (KDP, 5 +/- 4%), with the
      non-propulsive Tuck technique accounting for 24 +/- 4% of the course. Large
      within-athlete variances in CL and CR occurred, particularly for DS (CV% = 25 +/-
      2% and CV% = 15 +/- 2%, respectively). For all sub-techniques the mean CR on both
      laps and for the slower and faster skiers were similar, while there was a trend
      for the mean velocities in all sub-techniques by the faster athletes to be
      higher. Overall velocity and mean DP-CL were significantly higher on Lap 1, with
      no significant change in KDP-CL or DS-CL between laps. Distinct individual
      velocity thresholds for transitions between sub-techniques were observed.
      Clearly, valuable insights into cross-country skiing performance can be gained
      through continuous macro-kinematic monitoring during competition.

PMID- 28763505
TI  - Impact of a district-wide health center strengthening intervention on healthcare
      utilization in rural Rwanda: Use of interrupted time series analysis.
AB  - BACKGROUND: Evaluations of health systems strengthening (HSS) interventions using
      observational data are rarely used for causal inference due to limited data
      availability. Routinely collected national data allow use of quasi-experimental
      designs such as interrupted time series (ITS). Rwanda has invested in a robust
      electronic health management information system (HMIS) that captures monthly
      healthcare utilization data. We used ITS to evaluate impact of an HSS
      intervention to improve primary health care facility readiness on health service
      utilization in two rural districts of Rwanda. METHODS: We used controlled ITS
      analysis to compare changes in healthcare utilization at health centers (HC) that
      received the intervention (n = 13) to propensity score matched non-intervention
      health centers in Rwanda (n = 86) from January 2008 to December 2012. HC support
      included infrastructure renovation, salary support, medical equipment, referral
      network strengthening, and clinical training. Baseline quarterly mean outpatient
      visit rates and population density were used to model propensity scores. The
      intervention began in May 2010 and was implemented over a twelve-month period. We
      used monthly healthcare utilization data from the national Rwandan HMIS to study
      changes in the (1) number of facility deliveries per 10,000 women, (2) number of
      referrals for high risk pregnancy per 100,000 women, and (3) the number of
      outpatient visits performed per 1,000 catchment population. RESULTS: PHIT HC
      experienced significantly higher monthly delivery rates post-HSS during the April
      June season than comparison (3.19/10,000, 95% CI: [0.27, 6.10]). In 2010, this
      represented a 13% relative increase, and in 2011, this represented a 23% relative
      increase. The post-HSS change in monthly rate of high-risk pregnancies referred
      increased slightly in intervention compared to control HC (0.03/10,000, 95% CI: [
      0.007, 0.06]). There was a small immediate post-HSS increase in outpatient visit
      rates in intervention compared to control HC (6.64/1,000, 95% CI: [-13.52,
      26.81]). CONCLUSION: We failed to find strong evidence of post-HSS increases in
      outpatient visit rates or referral rates at health centers, which could be
      explained by small sample size and high baseline nation-wide health service
      coverage. However, our findings demonstrate that high quality routinely collected
      health facility data combined with ITS can be used for rigorous policy evaluation
      in resource-limited settings.

PMID- 28763506
TI  - The delta neutrophil index is a prognostic factor for postoperative mortality in
      patients with sepsis caused by peritonitis.
AB  - INTRODUCTION: The delta neutrophil index (DNI) represents the fraction of
      circulating immature granulocytes and is a marker of infection and sepsis. Our
      objective was to evaluate the usefulness of DNI for predicting in-hospital
      mortality within 30 days after surgery in patients with sepsis caused by
      peritonitis by means of comparing DNI, white blood cell (WBC) count, neutrophil
      percentage, and C-reactive protein (CRP) before and after surgery. MATERIALS AND
      METHODS: We performed a retrospective analysis of demographic, clinical, and
      laboratory data. DNI, WBC count, neutrophil percentage, and CRP were measured
      before surgery, and at 12-36 h (day 1) and 60-84 h (day 3) after surgery.
      RESULTS: There were 116 (73.7%) survivors and 44 (26.3%) non-survivors. The rates
      of septic shock, norepinephrine administration, renal replacement, mechanical
      ventilator therapy, and reoperation, the Simplified Acute Physiology Score-3
      (SAPS3), and the Sepsis-related Organ Failure Assessment (SOFA) score were
      greater in non-survivors. DNI on day 3 was better than the other laboratory
      variables for predicting mortality. DNI was correlated with the SAPS3 (r = .46, p
      = .00) and SOFA score (r = .45, p = .00). The optimal cut-off DNI for predicting
      mortality was 7.8% (sensitivity: 77.3%; specificity: 95.9%). In receiver
      operating characteristic curve analysis, DNI on day 3 was the best indicator of
      mortality (area under the curve: .880; 95% confidence interval: .80-.96).
      CONCLUSIONS: Our results indicate that DNI is better than other laboratory
      variables for predicting postoperative mortality in patients with sepsis caused
      by peritonitis. DNI > 7.8% on day 3 was a reliable predictor of postoperative
      mortality.

PMID- 28763507
TI  - Influence of muscle fiber type composition on early fat accumulation under high
      fat diet challenge.
AB  - OBJECTIVE: To investigate whether differences in muscle fiber types affect early
      stage fat accumulation, under high fat diet challenge in mice. METHODS: Twelve
      healthy male C57BL/6 mice experienced with short-term (6 weeks) diet treatment
      for the evaluation of early pattern changes in muscular fat. The mice were
      randomly divided into two groups: high fat diet (n = 8) and normal control diet
      (n = 4). Extra- and intra-myocellular lipid (EMCL and IMCL) in lumbar muscles
      (type I fiber predominant) and tibialis anterior (TA) muscle (type II fiber
      predominant) were determined using magnetic resonance spectroscopy (MRS).
      Correlation of EMCL, IMCL and their ratio between TA and lumbar muscles was
      evaluated. RESULTS: EMCL increased greatly in both muscle types after high fat
      diet. IMCL in TA and lumbar muscles increased to a much lower extent, with a
      slightly greater increase in TA muscles. EMCLs in the 2 muscles were positively
      correlated (r = 0.84, p = 0.01), but IMCLs showed a negative relationship (r = 
      0.84, p = 0.01). In lumbar muscles, high fat diet significantly decreased type I
      fiber while it increased type II fiber (all p<=0.001). In TA muscle, there was no
      significant fiber type shifting (p>0.05). CONCLUSIONS: Under short-time high fat
      diet challenge, lipid tends to initially accumulate extra-cellularly. In
      addition, compared to type II dominant muscle, Type I dominant muscle was less
      susceptible to IMCL accumulation but more to fiber type shifting. These phenomena
      might reflect compensative responses of skeletal muscle to dietary lipid overload
      in order to regulate metabolic homeostasis.

PMID- 28763508
TI  - Invasions but not extinctions change phylogenetic diversity of angiosperm
      assemblage on southeastern Pacific Oceanic islands.
AB  - We assessed changes in phylogenetic diversity of angiosperm flora on six oceanic
      islands located in the southeastern Pacific Ocean, by comparing flora from two
      periods: the pre-European colonization of islands and current times. We
      hypothesize that, in the time between these periods, extinction of local plant
      species and addition of exotic plants modified phylogenetic-alpha-diversity at
      different levels (deeper and terminal phylogeny) and increased phylo-beta
      diversity among islands. Based on floristic studies, we assembled a phylogenetic
      tree from occurrence data that includes 921 species, of which 165 and 756 were
      native or exotic in origin, respectively. Then, we studied change in the phylo
      alpha-diversity and phylo-beta-diversity (1 -Phylosor) by comparing pre-European
      and current times. Despite extinction of 18 native angiosperm species, an
      increase in species richness and phylo-alpha-diversity was observed for all
      islands studied, attributed to introduction of exotic plants (between 6 to 477
      species per island). We did not observe significant variation of mean
      phylogenetic distance (MPD), a measure of the 'deeper' phylogenetic diversity of
      assemblages (e.g., orders, families), suggesting that neither extinctions nor
      introductions altered phylogenetic structure of the angiosperms of these islands.
      In regard to phylo-beta-diversity, we detected temporal turnover (variation in
      phylogenetic composition) between periods to flora (0.38 +/- 0.11). However, when
      analyses were performed only considering native plants, we did not observe
      significant temporal turnover between periods (0.07 +/- 0.06). These results
      indicate that introduction of exotic angiosperms has contributed more notably
      than extinctions to the configuration of plant assemblages and phylogenetic
      diversity on the studied islands. Because phylogenetic diversity is closely
      related to functional diversity (species trait variations and roles performed by
      organisms), our results suggests that the introduction of exotic plants to these
      islands could have detrimental impacts for ecosystem functions and ecosystem
      services that islands provide (e.g. productivity).

PMID- 28763509
TI  - Mediterranean diet and cognitive health: Initial results from the Hellenic
      Longitudinal Investigation of Ageing and Diet.
AB  - BACKGROUND: The Mediterranean dietary pattern has been associated with a
      decreased risk of many degenerative diseases and cognitive function in
      particular; however, relevant information from Mediterranean regions, where the
      prototype Mediterranean diet is typically adhered to, have been very limited.
      Additionally, predefined Mediterranean diet (MeDi) scores with use of a priori
      cut-offs have been used very rarely, limiting comparisons between different
      populations and thus external validity of the associations. Finally, associations
      between individual components of MeDi (i.e., food groups, macronutrients) and
      particular aspects of cognitive performance have rarely been explored. We
      evaluated the association of adherence to an a priori defined Mediterranean
      dietary pattern and its components with dementia and specific aspects of
      cognitive function in a representative population cohort in Greece. METHODS:
      Participants from the Hellenic Longitudinal Investigation of Ageing and Diet
      (HELIAD), an on-going population-based study, exploring potential associations
      between diet and cognitive performance in a representative sample from Greek
      regions, were included in this analysis. Diagnosis of dementia was made by a full
      clinical and neuropsychological evaluation, while cognitive performance was
      assessed according to five cognitive domains (memory, language, attention-speed,
      executive functioning, visuospatial perception) and a composite cognitive score.
      Adherence to MeDi was evaluated by an a priori score (range 0-55), derived from a
      detailed food frequency questionnaire. RESULTS: Among 1,865 individuals (mean age
      73+/-6 years, 41% male), 90 were diagnosed with dementia and 223 with mild
      cognitive impairment. Each unit increase in the Mediterranean dietary score
      (MedDietScore) was associated with a 10% decrease in the odds for dementia.
      Adherence to the MeDi was also associated with better performance in memory,
      language, visuospatial perception and the composite cognitive score; the
      associations were strongest for memory. Fish consumption was negatively
      associated with dementia and cognitive performance positively associated with non
      refined cereal consumption. CONCLUSIONS: Our results suggest that adherence to
      the MeDi is associated with better cognitive performance and lower dementia rates
      in Greek elders. Thus, the MeDi in its a priori constructed prototype form may
      have cognitive benefits in traditional Mediterranean populations.

PMID- 28763511
TI  - Correction: The Malagarasi River Does Not Form an Absolute Barrier to Chimpanzee
      Movement in Western Tanzania.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0058965.].

PMID- 28763510
TI  - Chromosomal diversity and molecular divergence among three undescribed species of
      Neacomys (Rodentia, Sigmodontinae) separated by Amazonian rivers.
AB  - The Neacomys genus (Rodentia, Sigmodontinae) is distributed in the Amazon region,
      with some species limited to a single endemic area, while others may occur more
      widely. The number of species within the genus and their geographical boundaries
      are not known accurately, due to their high genetic diversity and difficulties in
      taxonomic identification. In this work we collected Neacomys specimens from both
      banks of the Tapajos River in eastern Amazon, and studied them using chromosome
      painting with whole chromosome probes of Hylaeamys megacephalus (HME; Rodentia,
      Sigmodontinae), and molecular analysis using haplotypes of mitochondrial genes
      COI and Cytb. Chromosome painting shows that Neacomys sp. A (NSP-A, 2n = 58/FN =
      68) and Neacomys sp. B (NSP-B, 2n = 54/FN = 66) differ by 11 fusion/fission
      events, one translocation, four pericentric inversions and four heterochromatin
      amplification events. Using haplotypes of the concatenated mitochondrial genes
      COI and Cyt b, Neacomys sp. (2n = 58/FN = 64 and 70) shows a mean divergence of
      6.2% for Neacomys sp. A and 9.1% for Neacomys sp. B, while Neacomys sp. A and
      Neacomys sp. B presents a medium nucleotide divergence of 7.4%. Comparisons were
      made with other published Neacomys data. The Tapajos and Xingu Rivers act as
      geographic barriers that define the distribution of these Neacomys species.
      Furthermore, our HME probes reveal four synapomorphies for the Neacomys genus
      (associations HME 20/[13,22]/4, 6a/21, [9,10]/7b/[9,10] and 12/[16,17]) and
      demonstrate ancestral traits of the Oryzomyini tribe (HME 8a and 8b, 18 and 25)
      and Sigmodontinae subfamily (HME 15 and 24), which can be used as taxonomic
      markers for these groups.

PMID- 28763513
TI  - Correction: EBV induces persistent NF-kappaB activation and contributes to
      survival of EBV-positive neoplastic T- or NK-cells.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0174136.].

PMID- 28763512
TI  - A glycan-based approach to therapeutic angiogenesis.
AB  - Angiogenesis, the sprouting of new blood vessels from existing vasculature,
      involves multiple complex biological processes, and it is an essential step for
      hemostasis, tissue healing and regeneration. Angiogenesis stimulants can
      ameliorate human disease conditions including limb ischemia, chronic wounds,
      heart disease, and stroke. The current strategies to improve the bioavailability
      of pro-angiogenic growth factors, including VEGF and FGF2, have remained largely
      unsuccessful. This study demonstrates that small molecules, termed click
      xylosides, can promote angiogenesis in the in vitro matrigel tube formation assay
      and the ex ovo chick chorioallantoic membrane assay, depending on their aglycone
      moieties. Xyloside treatment enhances network connectivity and cell
      survivability, thereby, maintaining the network structures on matrigel culture
      for an extended period of time. These effects were achieved via the secreted
      xyloside-primed glycosaminoglycans (GAG) chains that in part, act through an
      ERK1/2 mediated signaling pathway. Through the remodeling of GAGs in the
      extracellular matrix of endothelial cells, the glycan approach, involving
      xylosides, offers great potential to effectively promote therapeutic
      angiogenesis.

PMID- 28763514
TI  - Correction: An evolutionarily stable strategy and the critical point of hog
      futures trading entities based on replicator dynamic theory: 2006-2015 data for
      China's 22 provinces.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0172009.].

PMID- 28763515
TI  - Retrospective study of long-term outcomes of enzyme replacement therapy in Fabry
      disease: Analysis of prognostic factors.
AB  - Despite enzyme replacement therapy, disease progression is observed in patients
      with Fabry disease. Identification of factors that predict disease progression is
      needed to refine guidelines on initiation and cessation of enzyme replacement
      therapy. To study the association of potential biochemical and clinical
      prognostic factors with the disease course (clinical events, progression of
      cardiac and renal disease) we retrospectively evaluated 293 treated patients from
      three international centers of excellence. As expected, age, sex and phenotype
      were important predictors of event rate. Clinical events before enzyme
      replacement therapy, cardiac mass and eGFR at baseline predicted an increased
      event rate. eGFR was the most important predictor: hazard ratios increased from 2
      at eGFR <90 ml/min/1.73m2 to 4 at eGFR <30, compared to patients with an eGFR
      >90. In addition, men with classical disease and a baseline eGFR <60
      ml/min/1.73m2 had a faster yearly decline (-2.0 ml/min/1.73m2) than those with a
      baseline eGFR of >60. Proteinuria was a further independent risk factor for
      decline in eGFR. Increased cardiac mass at baseline was associated with the most
      robust decrease in cardiac mass during treatment, while presence of cardiac
      fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of
      other cardiovascular risk factors, hypertension significantly predicted the risk
      for clinical events. In conclusion, besides increasing age, male sex and
      classical phenotype, faster disease progression while on enzyme replacement
      therapy is predicted by renal function, proteinuria and to a lesser extent
      cardiac fibrosis and hypertension.

PMID- 28763516
TI  - Crystal structure of mimivirus uracil-DNA glycosylase.
AB  - Cytosine deamination induced by stresses or enzymatic catalysis converts
      deoxycytidine into deoxyuridine, thereby introducing a G to A mutation after DNA
      replication. Base-excision repair to correct uracil to cytosine is initiated by
      uracil-DNA glycosylase (UDG), which recognizes and eliminates uracil from DNA.
      Mimivirus, one of the largest known viruses, also encodes a distinctive UDG gene
      containing a long N-terminal domain (N-domain; residues 1-130) and a motif-I
      (residues 327-343), in addition to the canonical catalytic domain of family I
      UDGs (also called UNGs). To understand the structural and functional features of
      the additional segments, we have determined the crystal structure of UNG from
      Acanthamoeba polyphaga mimivirus (mvUNG). In the crystal structure of mvUNG,
      residues 95-130 in the N-domain bind to a hydrophobic groove in the catalytic
      domain, and motif-I forms a short beta-sheet with a positively charged surface
      near the active site. Circular dichroism spectra showed that residues 1-94 are in
      a random coil conformation. Deletion of the three additional fragments reduced
      the activity and thermal stability, compared to full-length mvUNG. The results
      suggested that the mvUNG N-domain and motif-I are required for its structural and
      functional integrity.

PMID- 28763517
TI  - Higher risk of gastrointestinal parasite infection at lower elevation suggests
      possible constraints in the distributional niche of Alpine marmots.
AB  - Alpine marmots Marmota marmota occupy a narrow altitudinal niche within high
      elevation alpine environments. For animals living at such high elevations where
      resources are limited, parasitism represents a potential major cost in life
      history. Using occupancy models, we tested if marmots living at higher elevation
      have a reduced risk of being infected with gastro-intestinal helminths, possibly
      compensating the lower availability of resources (shorter feeding season, longer
      snow cover and lower temperature) than marmots inhabiting lower elevations.
      Detection probability of eggs and oncospheres of two gastro-intestinal helminthic
      parasites, Ascaris laevis and Ctenotaenia marmotae, sampled in marmot feces, was
      used as a proxy of parasite abundance. As predicted, the models showed a negative
      relationship between elevation and parasite detectability (i.e. abundance) for
      both species, while there appeared to be a negative effect of solar radiance only
      for C. marmotae. Site-occupancy models are used here for the first time to model
      the constrains of gastrointestinal parasitism on a wild species and the
      relationship existing between endoparasites and environmental factors in a
      population of free-living animals. The results of this study suggest the future
      use of site-occupancy models as a viable tool to account for parasite imperfect
      detection in eco-parasitological studies, and give useful insights to further
      investigate the hypothesis of the contribution of parasite infection in
      constraining the altitudinal niche of Alpine marmots.

PMID- 28763518
TI  - Biomechanical comparison of pin and nitinol bone staple fixation to pin and
      tension band wire fixation for the stabilization of canine olecranon osteotomies.
AB  - OBJECTIVE: To compare the initial biomechanical properties of olecranon
      osteotomies stabilized with intramedullary pins and a Nitinol bone staple to
      osteotomies stabilized with pin and tension band wire fixation. STUDY DESIGN: Ex
      vivo mechanical evaluation on cadaveric bones. MATERIAL AND METHODS: Ten pairs of
      cadaveric forelimbs from skeletally mature Greyhounds with an olecranon osteotomy
      stabilized with either a pin and Nitinol bone staple or a pin and tension band
      wire. A single load to failure was applied to each specimen through the triceps
      tendon. Biomechanical properties were compared based on stiffness, yield load,
      and maximum load to failure and load at 2 mm of axial displacement. RESULTS:
      Specimens stabilized with the bone staple were biomechanically superior in all
      the variables tested. There was significantly greater stiffness (118.0 +/- 25.9
      N/mm versus 70.1 +/- 40.4 N/mm; p = 0.005), yield load (319.0 +/- 99.8 N versus
      238.0 +/- 42.5 N; p = 0.03), maximum load sustained (385.0 +/- 99.2 N versus
      287.0 +/- 37.4 N; p = 0.009), and load at 2 mm of axial displacement (218.0 +/-
      51.5 N versus 138.0 +/- 48.7 N; p = 0.002) in specimens stabilized with pins and
      a Nitinol bone staple than specimens stabilized with pin and tension band wire
      fixation. CLINICAL SIGNIFICANCE: The pin and Nitinol bone staple construct
      provides a biomechanically superior alternative to pin and tension band wire
      fixation for stabilization of olecranon osteotomies, and its use warrants further
      clinical investigation.

PMID- 28763519
TI  - Effects of nandrolone decanoate on time to consolidation of bone defects
      resulting from osteotomy for tibial tuberosity advancement.
AB  - STUDY DESIGN: Experimental study. OBJECTIVE: The aim of this study was to
      evaluate the effect of nandrolone decanoate (ND) on the time taken for bone
      consolidation in dogs undergoing tibial tuberosity advancement surgery (TTA).
      MATERIALS AND METHODS: Seventeen dogs that underwent TTA surgery were randomly
      divided into two groups: group C (TTA; 9 stifles), and group TTA+ND (TTA and
      systemic administration of ND; 8 stifles). Three observers (two radiologists and
      an orthopaedic surgeon), assessed bone consolidation by visual inspection of
      serial radiographs at intervals of 21 days following surgery. RESULTS: There were
      no differences in median weight and age between groups, nor between the medians
      of the variables right and left stifle. Only weight and age values were normally
      distributed. The other variables, right and left stifle and time to
      consolidation, showed non-normal distribution. Meniscal injury was present in all
      animals in group C and all animals in group TTA+ND. There was a significant
      difference between time to consolidation in groups C and TTA+ND (p <0.05). One
      animal in the group TTA+ND showed increased libido. Kappa agreement among
      observers on radiographs was 0.87. CONCLUSION: Administration of ND reduces time
      to bone consolidation in dogs undergoing TTA.

PMID- 28763520
TI  - Effect of a calcaneo-tibial screw on medial and lateral stability of the canine
      tarsocrural joint ex vivo.
AB  - OBJECTIVE: To evaluate the use of a temporary calcaneo-tibial screw for
      stabilization of the tarsocrural joint in dogs with surgically treated collateral
      ligament injury. METHODS: The degree of varus and valgus laxity of the
      tarsocrural joint in various states of injury and stabilization was measured in
      paired cadaveric limbs of Greyhound dogs. The angle of varus or valgus laxity was
      calculated following simulated collateral ligament injury (long collateral
      ligament only, long and short collateral ligaments, and bilateral long and short
      collateral ligaments) and stabilization with a calcaneo-tibial screw. RESULTS:
      The joint was significantly more stable after placement of a calcaneo-tibial
      screw compared to limbs with any combination of injured collateral ligaments.
      There was not a significant difference between stability of the intact limb
      compared to the injured limb with calcaneo-tibial screw fixation. CLINICAL
      SIGNIFICANCE: Calcaneo-tibial screw fixation appears to be an adequate method of
      stabilizing the tarsocrural joint following collateral ligament injury, and
      warrants clinical evaluation as a less expensive alternative to external skeletal
      fixation application. It is likely that this method would need to be supplemented
      with a cranial half cast to prevent screw failure during weight bearing.

PMID- 28763521
TI  - Correlation of dickkopf-1 concentrations in plasma and synovial fluid to the
      severity of radiographic signs of equine osteoarthritis.
AB  - OBJECTIVE: The purpose of this study was to determine whether there was a
      correlation between circulating and intra-synovial Dkk-1 and radiographic signs
      of equine osteoarthritis. METHODS: Circulating and intra-synovial Dkk-1 levels
      were measured in clinical cases using a commercially available human Dkk-1 ELISA.
      Radiographs were performed of the joints from which fluid was collected and these
      were assessed and scored by a boarded radiologist for joint narrowing,
      subchondral bone sclerosis, subchondral bone lysis, and periarticular modelling.
      Comparisons were made between radiographic scores and the concentrations of Dkk-1
      using a Kruskal-Wallis one-way ANOVA. Correlations were calculated using
      Kendall's statistic. RESULTS: A total of 42 synovial fluid samples from 21 horses
      were collected and used in the analysis. No significant correlation was
      identified between Dkk-1 concentrations and radiographic signs of osteoarthritis.
      Intra-synovial Dkk-1 concentrations were significantly greater (p <0.001) in low
      motion joints (mean concentration, 232.68 pg/mL; range, 109.07-317.17) when
      compared to high-motion joints (28.78 pg/mL; 0.05-186.44 pg/mL) (p <0.001).
      CLINICAL SIGNIFICANCE: Low motion joints have significantly higher concentrations
      of Dkk-1 compared to high motion joints. Further research is needed to establish
      the importance of this finding and whether potential diagnostic or therapeutic
      applications of Dkk-1 exist in the horse.

PMID- 28763522
TI  - Bone haemophilic pseudotumour of the ulna: A rare complication of haemophilia in
      a dog.
AB  - OBJECTIVES: This case report describes for the first time a bone haemophilic
      pseudotumour in a dog. CASE DESCRIPTION: A seven-month-old German Shepherd male
      dog was presented with the complaint of a forelimb weight-bearing lameness with
      major swelling that expanded dramatically after fine needle aspiration.
      Radiographs showed a large, well-defined ulnar diaphyseal cystic-like osteolytic
      lesion. Based on prolonged activated partial thromboplastin time (aPTT) and low
      factor VIII activity, haemophilia A was diagnosed. Bone scintigraphy, computed
      tomography, magnetic resonance imaging, and histological findings definitely
      ruled out malignant neoplasia or inflammation and strongly supported a bone
      haemophilic pseudotumour over an aneurysmal bone cyst. Segmental ulnar resection 
      and replacement by a polymethylmethacrylate spacer combined with perioperative
      bleeding management resulted in a successful outcome. DISCUSSION: This case
      provided evidence that a bone haemophilic pseudotumour may be the sole presenting
      clinical sign of haemophilia A in dogs. Early diagnosis, based on history and
      magnetic resonance imaging findings, is imperative for prompt treatment leading
      to successful outcome. It is challenging as fine needle aspiration or biopsy is
      contraindicated. As described in humans, surgical excision of the lesion combined
      with management of severe postoperative bleeding was associated with successful
      outcome in the present case. CLINICAL SIGNIFICANCE: A bone haemophilic
      pseudotumour should be considered in the differential diagnosis of expanding mass
      associated with osteolysis, especially in young male dogs. Perioperative
      monitoring of the bleeding disorder and subsequent FVIII replacement therapy was
      of paramount importance in the present case.

PMID- 28763523
TI  - Efficacy of an oral nutraceutical for the treatment of canine osteoarthritis. A
      double-blind, randomized, placebo-controlled prospective clinical trial.
AB  - OBJECTIVES: To assess the safety and efficacy of an orally administered
      nutraceutical (Glu/CS+; + for additional ingredient) for the treatment of
      clinical osteoarthritis (OA) in dogs. METHODS: In this double-blind, randomized,
      placebo-controlled clinical trial, client-owned dogs with clinical signs of OA in
      one or more joints were assigned to a Glu/CS+ (n = 30) or placebo (n = 30) group.
      Dogs were administered Glu/CS+ or placebo orally and wore an activity monitor
      (AM) continuously throughout a 97 day study period. Prior to the initiation of
      the treatment, seven days of baseline activity was collected. On days -7, 30, 60
      and 90 of the study, owners completed a patient assessment form (Canine Brief
      Pain Inventory). Data between groups were compared. RESULTS: No serious adverse
      events were reported. No difference was found between groups when evaluating
      daily activity counts during the seven-day pre-treatment period and the 90-day
      treatment period. Owner assessment (pain interference and pain severity scores)
      improved over the 90-day treatment period for both groups, however no difference
      was found between treatment groups. CONCLUSIONS: Treatment with oral Glu/CS+ for
      a 90 day treatment period when compared to placebo treatment did not result in a
      significant increase in activity counts in dogs with clinical OA. However, owner
      assessment scores similarly improved throughout the study period for dogs in both
      groups, suggesting a caregiver placebo effect in this outcome measure.

PMID- 28763524
TI  - The influence of aluminium, steel and polyurethane shoeing systems and of the
      unshod hoof on the injury risk of a horse kick. An ex vivo experimental study.
AB  - OBJECTIVES: To evaluate the damage inflicted by an unshod hoof and by the various
      horseshoe materials (steel, aluminium and polyurethane) on the long bones of
      horses after a simulated kick. METHODS: Sixty-four equine radii and tibiae were
      evaluated using a drop impact test setup. An impactor with a steel, aluminium,
      polyurethane, or hoof horn head was dropped onto prepared bones. An impactor
      velocity of 8 m/s was initially used with all four materials and then testing was
      repeated with a velocity of 12 m/s with the polyurethane and hoof horn heads. The
      impact process was analysed using a high-speed camera, and physical parameters,
      including peak contact force and impact duration, were calculated. RESULTS: At 8
      m/s, the probability of a fracture was 75% for steel and 81% for aluminium,
      whereas polyurethane and hoof horn did not damage the bones. At 12 m/s, the
      probability of a fracture was 25% for polyurethane and 12.5% for hoof horn. The
      peak contact force and impact duration differed significantly between 'hard
      materials' (aluminium and steel) and 'soft materials' (polyurethane and hoof
      horn). CLINICAL SIGNIFICANCE: The observed bone injuries were similar to those
      seen in analogous experimental studies carried out previously and comparable to
      clinical fracture cases suggesting that the simulated kick was realistic. The
      probability of fracture was significantly higher for steel and aluminium than for
      polyurethane and hoof horn, which suggests that the horseshoe material has a
      significant influence on the risk of injury for humans or horses kicked by a
      horse.

PMID- 28763525
TI  - Prevalence, treatment and outcome of patellar luxation in dogs in Italy. A
      retrospective multicentric study (2009-2014).
AB  - OBJECTIVE: To determine the prevalence of patellar luxation in dogs in Italy and
      its relation to signalment, the frequency and the type of postoperative
      complications and the outcome of treatment, and to compare the findings with
      those of other studies. MATERIALS AND METHODS: The medical records from four
      referral clinics were searched for dogs with orthopaedic disorders referred from
      2009 to 2014. From these data, the records of dogs with patellar luxation were
      identified, and the signalment, age and body weight, grade, side and direction of
      patellar luxation, treatment, postoperative complications, and outcome were
      retrieved. Univariate and multivariate statistical analyses were used to evaluate
      the data. RESULTS: Of 8,694 canine orthopaedic cases, fractures not included,
      patellar luxation was diagnosed in 559 dogs (801 stifles). Mixed breed dogs were
      most commonly affected (18%), 85% of the luxations were medial, and 52% of the
      dogs were female. Of the 559 dogs examined, 400 (574 stifles) met the inclusion
      criteria for treatment evaluation. Minor complications occurred in five percent
      of the dogs, and major complications in 16%, including recurrence of patellar
      luxation in seven percent of the dogs. The outcome was good in 88% of stifles,
      fair in two percent, and poor in 10%. CLINICAL SIGNIFICANCE: Although patellar
      luxation was more common in small breed dogs, it also was diagnosed in a
      significant number of large breed dogs, which included medial patellar luxation
      in 73% and lateral patellar luxation in 27% of stifles. Body weight and grade of
      luxation were the only variables statistically correlated with surgical
      complications.

PMID- 28763526
TI  - Bacterial recovery using sonication versus swabbing of titanium and stainless
      steel implants inoculated with Staphylococcus pseudintermedius or Pseudomonas
      aeruginosa.
AB  - OBJECTIVE: To evaluate the use of sonication to improve recovery of bacteria from
      metal discs infected with bacteria commonly associated with implant infections in
      veterinary medicine. METHODS: In vitro study in which sterile titanium (Ti6Al4V)
      and stainless steel (AIS1316-L) discs were incubated with either Staphylococcus
      pseudintermedius or Pseudomonas aeruginosa for 24 hours. The following three
      groups were compared: 1) the sonication group involved immersing the discs in
      sterile saline and sonicating for five minutes; 2) the sham group was considered
      a negative control in which the discs were immersed in saline for five minutes
      without sonication; and 3) the swab group involved systematically swabbing the
      implant with a sterile culturette. All samples were plated on blood agar and
      incubated for 24 hours. Colonies were then counted and compared. RESULTS: For
      both species of bacteria, there was a significant increase in bacterial colonies
      isolated using sonication compared to the other two study groups (p = 0.0001). No
      differences in bacterial growth were found between the two types of metal
      implants. There was a significant increase in bacterial colony counts for S.
      pseudintermedius when comparing the swab group versus the sham group, but this
      was not significant for P. aeruginosa. CLINICAL SIGNIFICANCE: Sonication
      significantly improves recovery of bacteria commonly associated with veterinary
      implant-associated surgical site infections compared to swabbing of implants in
      vitro. A prospective clinical evaluation is indicated to determine the in vivo
      efficacy of sonication in veterinary patients.

PMID- 28763527
TI  - Speed-size illusion correlates with retinal-level motion statistics.
AB  - It is a common perceptual experience that smaller objects appear to move faster
      than larger ones when their physical speeds are the same in either the laboratory
      or daily life. In this study, we show that the speed-size illusion is correlated
      with retinal image speed distribution bias. The illusion was quantified with a
      two-alternative, forced choice speed comparison paradigm, and retinal image speed
      distributions for different image sizes were obtained by simulation. Simulation
      results show that smaller retinal images tend to have slower projected speed, and
      the retinal image speed distribution bias correlates with the strength of the
      speed-size illusion. Furthermore, exposure to a training movie containing
      unnatural motion statistics tended to modulate the illusion in a way that was
      consistent with the speed distribution bias. We discuss how the data could be
      explained by empirical ranking theory, Bayesian theory, and motion adaptation.

PMID- 28763528
TI  - CRISPR-Based System Uncovers Key Regulators of Disease-Related Genes.

PMID- 28763529
TI  - 24-Hour Urine Calcium in the Evaluation and Management of Nephrolithiasis.

PMID- 28763530
TI  - Corticosteroids for IgA Nephropathy: TESTING for Benefit, Discovering Harm.

PMID- 28763531
TI  - New Hereditary Angioedema Therapy.

PMID- 28763532
TI  - Another Fluoroquinolone Approved.

PMID- 28763533
TI  - Extended-Release ADHD Drug.

PMID- 28763535
TI  - Costs and Outcomes of Mental Health and Substance Use Disorders in the US.

PMID- 28763534
TI  - Viral Testing for Pediatric Respiratory Infections: Why Precise Diagnoses Do Not
      Always Translate to Patient Benefit.

PMID- 28763537
TI  - State Flexibility for Medicaid: How Much?

PMID- 28763538
TI  - Medical News: London Letter.

PMID- 28763539
TI  - Fees for Certification and Finances of Medical Specialty Boards.

PMID- 28763540
TI  - Dexmedetomidine in Patients With Sepsis Requiring Mechanical Ventilation.

PMID- 28763541
TI  - Exercise for Patients With Hypertrophic Cardiomyopathy.

PMID- 28763542
TI  - Risks of Medical Metaphors.

PMID- 28763543
TI  - Time to Diagnostic Testing After a Positive Colorectal Cancer Screening Test.

PMID- 28763544
TI  - Dexmedetomidine in Patients With Sepsis Requiring Mechanical Ventilation-Reply.

PMID- 28763545
TI  - Exercise for Patients With Hypertrophic Cardiomyopathy-Reply.

PMID- 28763546
TI  - Risks of Medical Metaphors-Reply.

PMID- 28763547
TI  - Time to Diagnostic Testing After a Positive Colorectal Cancer Screening Test
      Reply.

PMID- 28763549
TI  - Association of Practice-Level Social and Medical Risk With Performance in the
      Medicare Physician Value-Based Payment Modifier Program.
AB  - Importance: Medicare recently launched the Physician Value-Based Payment Modifier
      (PVBM) Program, a mandatory pay-for-performance program for physician practices.
      Little is known about performance by practices that serve socially or medically
      high-risk patients. Objective: To compare performance in the PVBM Program by
      practice characteristics. Design, Setting, and Participants: Cross-sectional
      observational study using PVBM Program data for payments made in 2015 based on
      performance of large US physician practices caring for fee-for-service Medicare
      beneficiaries in 2013. Exposures: High social risk (defined as practices in the
      top quartile of proportion of patients dually eligible for Medicare and Medicaid)
      and high medical risk (defined as practices in the top quartile of mean
      Hierarchical Condition Category risk score among fee-for-service beneficiaries).
      Main Outcomes and Measures: Quality and cost z scores based on a composite of
      individual measures. Higher z scores reflect better performance on quality; lower
      scores, better performance on costs. Results: Among 899 physician practices with
      5 189 880 beneficiaries, 547 practices were categorized as low risk (neither high
      social nor high medical risk) (mean, 7909 beneficiaries; mean, 320 clinicians),
      128 were high medical risk only (mean, 3675 beneficiaries; mean, 370 clinicians),
      102 were high social risk only (mean, 1635 beneficiaries; mean, 284 clinicians),
      and 122 were high medical and social risk (mean, 1858 beneficiaries; mean, 269
      clinicians). Practices categorized as low risk performed the best on the
      composite quality score (z score, 0.18 [95% CI, 0.09 to 0.28]) compared with each
      of the practices categorized as high risk (high medical risk only: z score, -0.55
      [95% CI, -0.77 to -0.32]; high social risk only: z score, -0.86 [95% CI, -1.17 to
      -0.54]; and high medical and social risk: -0.78 [95% CI, -1.04 to -0.51]) (P <
      .001 across groups). Practices categorized as high social risk only performed the
      best on the composite cost score (z score, -0.52 [95% CI, -0.71 to -0.33]), low
      risk had the next best cost score (z score, -0.18 [95% CI, -0.25 to -0.10]), then
      high medical and social risk (z score, 0.40 [95% CI, 0.23 to 0.57]), and then
      high medical risk only (z score, 0.82 [95% CI, 0.65 to 0.99]) (P < .001 across
      groups). Total per capita costs were $9506 for practices categorized as low risk,
      $13 683 for high medical risk only, $8214 for high social risk only, and $11 692
      for high medical and social risk. These patterns were associated with fewer
      bonuses and more penalties for high-risk practices. Conclusions and Relevance:
      During the first year of the Medicare Physician Value-Based Payment Modifier
      Program, physician practices that served more socially high-risk patients had
      lower quality and lower costs, and practices that served more medically high-risk
      patients had lower quality and higher costs.

PMID- 28763548
TI  - Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA
      Nephropathy: The TESTING Randomized Clinical Trial.
AB  - Importance: Guidelines recommend corticosteroids in patients with IgA nephropathy
      and persistent proteinuria, but the effects remain uncertain. Objective: To
      evaluate the efficacy and safety of corticosteroids in patients with IgA
      nephropathy at risk of progression. Design, Setting, and Participants: The
      Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was
      a multicenter, double-blind, randomized clinical trial designed to recruit 750
      participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated
      glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m2 after at least 3
      months of blood pressure control with renin-angiotensin system blockade] and to
      provide follow-up until 335 primary outcomes occurred. Interventions: Patients
      were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48
      mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent
      weaning over 4 to 6 months. Main Outcomes and Measures: The primary composite
      outcome was end-stage kidney disease, death due to kidney failure, or a 40%
      decrease in eGFR. Predefined safety outcomes were serious infection, new
      diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular
      events. The mean required follow-up was estimated to be 5 years. Results: After
      randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%]
      women; eGFR, 59.4 mL/min/1.73 m2; urine protein excretion, 2.40 g/d) and 2.1
      years' median follow-up, recruitment was discontinued because of excess serious
      adverse events. Serious events occurred in 20 participants (14.7%) in the
      methylprednisolone group vs 4 (3.2%) in the placebo group (P = .001; risk
      difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections
      (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P < .001), including
      2 deaths. The primary renal outcome occurred in 8 participants (5.9%) in the
      methylprednisolone group vs 20 (15.9%) in the placebo group (hazard ratio, 0.37
      [95% CI, 0.17-0.85]; risk difference, 10.0% [95% CI, 2.5%-17.9%]; P = .02).
      Conclusions and Relevance: Among patients with IgA nephropathy and proteinuria of
      1 g/d or greater, oral methylprednisolone was associated with an increased risk
      of serious adverse events, primarily infections. Although the results were
      consistent with potential renal benefit, definitive conclusions about treatment
      benefit cannot be made, owing to early termination of the trial. Trial
      Registration: clinicaltrials.gov Identifier: NCT01560052.

PMID- 28763551
TI  - Childhood Pneumonia.

PMID- 28763550
TI  - Effect of Endovascular Contact Aspiration vs Stent Retriever on Revascularization
      in Patients With Acute Ischemic Stroke and Large Vessel Occlusion: The ASTER
      Randomized Clinical Trial.
AB  - Importance: The benefits of endovascular revascularization using the contact
      aspiration technique vs the stent retriever technique in patients with acute
      ischemic stroke remain uncertain because of lack of evidence from randomized
      trials. Objective: To compare efficacy and adverse events using the contact
      aspiration technique vs the standard stent retriever technique as a first-line
      endovascular treatment for successful revascularization among patients with acute
      ischemic stroke and large vessel occlusion. Design, Setting, and Participants:
      The Contact Aspiration vs Stent Retriever for Successful Revascularization
      (ASTER) study was a randomized, open-label, blinded end-point clinical trial
      conducted in 8 comprehensive stroke centers in France (October 2015-October
      2016). Patients who presented with acute ischemic stroke and a large vessel
      occlusion in the anterior circulation within 6 hours of symptom onset were
      included. Interventions: Patients were randomly assigned to first-line contact
      aspiration (n = 192) or first-line stent retriever (n = 189) immediately prior to
      mechanical thrombectomy. Main Outcomes and Measures: The primary outcome was the
      proportion of patients with successful revascularization defined as a modified
      Thrombolysis in Cerebral Infarction score of 2b or 3 at the end of all
      endovascular procedures. Secondary outcomes included degree of disability
      assessed by overall distribution of the modified Rankin Scale (mRS) score at 90
      days, change in National Institutes of Health Stroke Scale (NIHSS) score at 24
      hours, all-cause mortality at 90 days, and procedure-related serious adverse
      events. Results: Among 381 patients randomized (mean age, 69.9 years; 174 women
      [45.7%]), 363 (95.3%) completed the trial. Median time from symptom onset to
      arterial puncture was 227 minutes (interquartile range, 180-280 minutes). For the
      primary outcome, the proportion of patients with successful revascularization was
      85.4% (n = 164) in the contact aspiration group vs 83.1% (n = 157) in the stent
      retriever group (odds ratio, 1.20 [95% CI, 0.68-2.10]; P = .53; difference, 2.4%
      [95% CI, -5.4% to 9.7%]). For the clinical efficacy outcomes (change in NIHSS
      score at 24 hours, mRS score at 90 days) and adverse events, there were no
      significant differences between groups. Conclusions and Relevance: Among patients
      with ischemic stroke in the anterior circulation undergoing thrombectomy, first
      line thrombectomy with contact aspiration compared with stent retriever did not
      result in an increased successful revascularization rate at the end of the
      procedure. Trial Registration: clinicaltrials.gov Identifier: NCT02523261.

PMID- 28763553
TI  - The Paradox of Mindfulness: Seamus Heaney's "St Kevin and the Blackbird".

PMID- 28763554
TI  - Does This Child Have Pneumonia?: The Rational Clinical Examination Systematic
      Review.
AB  - Importance: Pneumonia is a leading cause of morbidity and mortality in children.
      It is important to identify the clinical symptoms and physical examination
      findings associated with pneumonia to improve timely diagnosis, prevent
      significant morbidity, and limit antibiotic overuse. Objective: To systematically
      review the accuracy of symptoms and physical examination findings in identifying
      children with radiographic pneumonia. Data Sources and Study Selection: MEDLINE
      and Embase (1956 to May 2017) were searched, along with reference lists from
      retrieved articles, to identify diagnostic studies of pediatric pneumonia across
      a broad age range that had to include children younger than age 5 years (although
      some studies enrolled children up to age 19 years); 3644 unique articles were
      identified, of which 23 met inclusion criteria. Data Extraction and Synthesis:
      Two authors independently abstracted raw data and assessed methodological
      quality. A third author resolved disputes. Main Outcomes and Measures: Likelihood
      ratios (LRs), sensitivity, and specificity were calculated for individual
      symptoms and physical examination findings for the diagnosis of pneumonia. An
      infiltrate on chest radiograph was considered the reference standard for the
      diagnosis of pneumonia. Results: Twenty-three prospective cohort studies of
      children (N = 13 833) with possible pneumonia were included (8 from North
      America), with a range of 78 to 2829 patients per study. The prevalence of
      radiographic pneumonia in North American studies was 19% (95% CI, 11%-31%) and
      37% (95% CI, 26%-50%) outside of North America. No single symptom was strongly
      associated with pneumonia; however, the presence of chest pain in 2 studies that
      included adolescents was associated with pneumonia (LR, 1.5-5.5; sensitivity, 8%
      14%; specificity, 94%-97%). Vital sign abnormalities such as fever (temperature
      >37.5 degrees C [LR range, 1.7-1.8]; sensitivity, 80%-92%; specificity, 47%-54%)
      and tachypnea (respiratory rate >40 breaths/min; LR, 1.5 [95% CI, 1.3-1.7];
      sensitivity, 79%; specificity, 51%) were not strongly associated with pneumonia
      diagnosis. Similarly, auscultatory findings were not associated with pneumonia
      diagnosis. The presence of moderate hypoxemia (oxygen saturation <=96%; LR, 2.8
      [95% CI, 2.1-3.6]; sensitivity, 64%; specificity, 77%) and increased work of
      breathing (grunting, flaring, and retractions; positive LR, 2.1 [95% CI, 1.6
      2.7]) were signs most associated with pneumonia. The presence of normal
      oxygenation (oxygen saturation >96%) decreased the likelihood of pneumonia (LR,
      0.47 [95% CI, 0.32-0.67]). Conclusions and Relevance: Although no single finding
      reliably differentiates pneumonia from other causes of childhood respiratory
      illness, hypoxia and increased work of breathing are more important than
      tachypnea and auscultatory findings.

PMID- 28763556
TI  - Modifications in Retinal Mitochondrial Respiration Precede Type 2 Diabetes and
      Protracted Microvascular Retinopathy.
AB  - Purpose: To characterize retinal mitochondrial respiration associated with type 2
      diabetes (T2D) progression in a cone-rich diurnal rodent, the Nile rat (genus
      Arvicanthis, species niloticus). Methods: Nile rats were fed a standard rodent
      diet that resulted in rising glucose levels from 6 months. Age-matched control
      animals were fed a high-fiber diet that prevented diabetes up to 18 months. The
      functional status of specific retinal mitochondrial components and mitochondrial
      outer membrane integrity were studied by using high-resolution respirometry.
      Ocular complications were documented with funduscopy, electroretinography (ERG),
      and trypsin digestion of retinal vasculature. Results: Mitochondrial functional
      changes were detected during hyperinsulinemia with maintained normoglycemia (2
      months), corresponding to stage 1 of human T2D. Our data showed increased
      contribution of mitochondrial respiration through the NADH pathway relative to
      maximal oxidative phosphorylation capacity, with simultaneous electron entry into
      NADH (Complex I and related dehydrogenases) and succinate (Complex II) pathways.
      These compensatory events coincided with compromised mitochondrial outer membrane
      integrity. The first clinical sign of retinopathy (pericyte loss) was only
      detected at 12 months (after 6 months of sustained hyperglycemia) alongside a
      common ocular complication of diabetes, cataractogenesis. Further prolongation of
      hyperglycemia (from 12 to 18 months) led to capillary degeneration and delayed
      photopic ERG oscillatory potentials. Conclusions: Oxidative phosphorylation
      compensatory changes in the retina can be detected as early as 2 months, before
      development of hyperglycemia, and are associated with reduced mitochondrial outer
      membrane integrity.

PMID- 28763557
TI  - C2orf71 Mutations as a Frequent Cause of Autosomal-Recessive Retinitis
      Pigmentosa: Clinical Analysis and Presentation of 8 Novel Mutations.
AB  - Purpose: To define the phenotype of C2orf71 associated retinopathy and to present
      novel mutations in this gene. Methods: A retrospective multicenter study of
      patients with retinopathy and identified C2orf71 mutations was performed. Ocular
      function (visual acuity, visual fields, electroretinogram [ERG] responses);
      retinal morphology (fundus, optical coherence tomography); and underlying
      mutations were analyzed. Results: Thirteen patients from 11 families, who were
      aged 7 to 63 years (mean: 32.1 years) at their first examination with presumed
      compound heterozygous (6/13 patients) or homozygous (7/13 patients) C2orf71
      mutations were identified. Eight of the mutations were novel. Truncation
      mutations were responsible in all cases. Nyctalopia was observed in less than 50%
      of patients. Visual acuity ranged from 20/20 to light perception. Severe visual
      loss was associated with atrophic maculopathy. Full-field ERG responses showed
      severe progressive cone-rod or rod-cone dysfunction. Typical fundus changes were
      progressive symmetrical retinopathy with an early mild maculopathy and patchy
      circular midperipheral RPE atrophy. Normal retinal lamination was preserved
      despite early disruption of the ellipsoid zone and RPE irregularities. Outer
      retinal tubulations were associated with better-preserved visual acuity.
      Conclusions: On the basis of our multicenter analysis, C2orf71 might represent a
      more frequently mutated gene in autosomal recessive retinitis pigmentosa in some
      populations. The phenotype analysis over a wide age range showed a variable and
      progressive retinal degeneration with early onset maculopathy and a better visual
      potential before the age of 30 years.

PMID- 28763558
TI  - Radiation Maculopathy After Proton Beam Therapy for Uveal Melanoma: Optical
      Coherence Tomography Angiography Alterations Influencing Visual Acuity.
AB  - Purpose: To analyze microvascular and structural changes in radiation maculopathy
      and their influence on visual acuity (VA), using optical coherence tomography
      (OCT) and OCT angiography (OCTA). Methods: This was a retrospective analysis of
      consecutive patients with radiation maculopathy, 12 months or more after proton
      beam irradiation for uveal melanoma, imaged with fluorescein angiography, OCT,
      and OCTA. Clinical parameters potentially affecting VA were recorded, including
      OCTA-derived metrics: foveal avascular zone (FAZ) area, vascular density, and
      local fractal dimension of the superficial (SCP) and deep capillary plexuses
      (DCP). Nonirradiated fellow eyes served as controls. Results: Ninety-three
      patients were included. FAZ was larger, while SCP/DCP capillary density and local
      fractal dimension were lower in the 35 irradiated than in the 35 fellow eyes (P <
      0.0001). Microvascular alterations graded on fluorescein angiography (minimally
      damaged/disrupted/disorganized) were correlated to FAZ area and SCP/DCP density
      on OCTA (P < 0.01). By univariate analysis, worse VA was associated to macular
      detachment at presentation (P = 0.024), total macular irradiation (P = 0.0008),
      higher central macular thickness (CMT) (P = 0.019), higher absolute CMT variation
      (P < 0.0001), cystoid edema (P = 0.030), ellipsoid zone disruption (P = 0.002),
      larger FAZ (P < 0.0001), lower SCP (P = 0.001) and DCP capillary density (P <
      0.0001), and lower SCP (P = 0.009) and DCP local fractal dimension (P < 0.0001).
      Two multivariate models with either capillary density or fractal dimension as
      covariate showed that younger age (P = 0.014/0.017), ellipsoid zone disruption (P
      = 0.034/0.019), larger FAZ (P = 0.0006/0.002), and lower DCP density (P = 0.008)
      or DCP fractal dimension (P = 0.012), respectively, were associated with worse
      VA. Conclusions: VA of eyes with radiation maculopathy is influenced by
      structural and microvascular factors identified with OCTA, including FAZ area and
      DCP integrity.

PMID- 28763560
TI  - Choroidal Vasculature in Bietti Crystalline Dystrophy With CYP4V2 Mutations and
      in Retinitis Pigmentosa With EYS Mutations.
AB  - Purpose: We compare the choroidal vascular area between Bietti crystalline
      dystrophy (BCD) patients with CYP4V2 mutations, retinitis pigmentosa (RP)
      patients with EYS mutations, and normal controls, and investigate the correlation
      between choroidal vascular area and associated parameters. Methods: This
      prospective case-series study included consecutive nine eyes of nine BCD patients
      with CYP4V2 mutations (BCD group), 16 eyes of 16 RP patients with EYS mutations
      (EYS-RP group), and 16 eyes of 16 normal volunteers matched for age and axial
      length (control group). Using swept-source optical coherence tomography, we
      obtained en face images of the choroidal vasculature at the midpoint of the
      choriocapillaris layer-Sattler's layer (inner choroid) and Haller's layer (outer
      choroid). After binarization, we compared the inner and outer choroidal vascular
      areas among the three groups and identified associated factors. Results: The
      outer choroidal vascular area was 43.34 +/- 5.76%, 53.73 +/- 4.92%, and 52.80 +/-
      4.10% in the BCD, EYS-RP, and control groups, respectively. This value was
      significantly smaller in the BCD group than in the EYS-RP and control groups (P <
      0.001 in both; no significant difference between the EYS-RP and control groups).
      In the BCD group, the outer choroidal vascular area was correlated strongly with
      the subfoveal inner choroidal thickness (P = 0.001, r = 0.91, respectively). The
      inner choroidal vasculature could not be identified in eight of nine eyes in the
      BCD group. Conclusions: The outer choroidal vascular narrowing might progress
      with the inner choroidal thinning in BCD, and the inner choroidal vasculature
      might be extinguished in advanced-stage BCD. Our findings may help to clarify the
      etiology of BCD.

PMID- 28763559
TI  - Adiponectin Mediates Dietary Omega-3 Long-Chain Polyunsaturated Fatty Acid
      Protection Against Choroidal Neovascularization in Mice.
AB  - Purpose: Neovascular age-related macular degeneration (AMD) is a major cause of
      legal blindness in the elderly. Diets with omega3-long-chain-polyunsaturated
      fatty-acid (omega3-LCPUFA) correlate with a decreased risk of AMD. Dietary omega3
      LCPUFA versus omega6-LCPUFA inhibits mouse ocular neovascularization, but the
      underlying mechanism needs further exploration. The aim of this study was to
      investigate if adiponectin (APN) mediated omega3-LCPUFA suppression of neovessels
      in AMD. Methods: The mouse laser-induced choroidal neovascularization (CNV) model
      was used to mimic some of the inflammatory aspect of AMD. CNV was compared
      between wild-type (WT) and Apn-/- mice fed either otherwise matched diets with 2%
      omega3 or 2% omega6-LCPUFAs. Vldlr-/- mice were used to mimic some of the
      metabolic aspects of AMD. Choroid assay ex vivo and human retinal microvascular
      endothelial cell (HRMEC) proliferation assay in vitro was used to investigate the
      APN pathway in angiogenesis. Western blot for p-AMPKalpha/AMPKalpha and qPCR for
      Apn, Mmps, and IL-10 were used to define mechanism. Results: omega3-LCPUFA intake
      suppressed laser-induced CNV in WT mice; suppression was abolished with APN
      deficiency. omega3-LCPUFA, mediated by APN, decreased mouse Mmps expression. APN
      deficiency decreased AMPKalpha phosphorylation in vivo and exacerbated choroid
      sprouting ex vivo. APN pathway activation inhibited HRMEC proliferation and
      decreased Mmps. In Vldlr-/- mice, omega3-LCPUFA increased retinal AdipoR1 and
      inhibited NV. omega3-LCPUFA decreased IL-10 but did not affect Mmps in Vldlr-/-
      retinas. Conclusions: APN in part mediated omega3-LCPUFA inhibition of
      neovascularization in two mouse models of AMD. Modulating the APN pathway in
      conjunction with a omega3-LCPUFA-enriched-diet may augment the beneficial effects
      of omega3-LCPUFA in AMD patients.

PMID- 28763561
TI  - Establishment and Characterization of an Acute Model of Ocular Hypertension by
      Laser-Induced Occlusion of Episcleral Veins.
AB  - Purpose: This study was designed to develop and characterize a laser-induced
      model of acute intraocular hypertension that permits the study of the anterior
      segment of the eye. Methods: CD1 mice aged 5 and 8 weeks were examined for
      elevation of IOP induced by laser photocoagulation. We compared between occlusion
      of episcleral veins alone and when combined with 270 degrees  limbal vessel
      occlusion. Anterior chamber angle, corneal thickness, and retinal nerve fiber
      layer (RNFL) thickness were evaluated by anterior- and posterior-segment optical
      coherence tomography (OCT). Additionally, at day 7 post-procedure, the anterior
      segment was evaluated for inflammatory cellular presentation by histologic
      analysis and OCT, and limbal vessels and whole-mount retina were immunostained
      for CD31 and Brn3a, respectively. Brn3a-positive retinal ganglion cells (RGCs)
      were quantified with ImageJ software. Results: After single or combined laser
      treatment in mice aged 5 or 8 weeks, IOP was significantly elevated for 5 to 6
      days before returning to the baseline by day 7 post-procedure. Anterior segment
      assessment indicated less synechiae in the anterior chamber angle and better
      preserved limbal vessels with single versus combined laser treatment. Corneal
      thickness was significantly increased after single or combined treatment. No
      inflammatory cells were detected in the anterior chamber. The thickness of the
      RNFL and the density of RGCs were both significantly reduced after single or
      combined treatment. Conclusions: Laser photocoagulation of episcleral veins alone
      in CD1 mice aged 5 to 8 weeks may be used to induce ocular hypertension resulting
      in RNFL thinning and ganglion cell loss. This model permits the study of the
      anterior as well as the posterior segment of the eye.

PMID- 28763562
TI  - Chondroitin Sulfate-Based Biocompatible Crosslinker Restores Corneal Mechanics
      and Collagen Alignment.
AB  - Purpose: To evaluate the crosslinking effect of functionalized chondroitin
      sulfate (CS) in an ex vivo rabbit cornea model. Methods: Chondroitin sulfate
      molecules were chemically modified with the N-hydroxysuccinimide (NHS) group.
      Enucleated rabbit eyes were crosslinked with 2, 5, or 10 mg/mL CS-NHS solution
      for 30 or 60 minutes. The CS-NHS penetration, corneal swelling ratio, Young's
      modulus, and ultrastructure of the crosslinked corneas were characterized. In
      addition, rabbit corneas were further treated with a collagenase-chondroitinase
      solution to create an ex vivo keratoconus (KC)-like model. The KC model corneas
      were crosslinked with a standard riboflavin-ultraviolet (UV) method or
      alternatively with CS-NHS. Corneal mechanics, ultrastructure, and keratocyte gene
      expression were evaluated after UV and CS-NHS crosslinking. Results: CS-NHS
      effectively penetrated into the corneal stroma within 60 minutes of treatment
      initiation. CS-NHS crosslinking reduced the swelling ratio by 35%, increased
      Young's modulus by 20%, and increased collagen fibril diameter and density. CS
      NHS crosslinking improved corneal mechanics of KC model corneas to levels
      comparable to those with UV crosslinking. Moreover, CS-NHS crosslinking
      demonstrated significant downregulation of proinflammatory gene expression of
      keratocytes, indicating a potential protective effect imparted by CS-NHS during
      crosslinking. Conclusions: Our results demonstrated that CS-NHS can reinforce
      normal and KC model corneal mechanics, and restore collagen density and alignment
      in KC model corneas without causing extensive keratocyte apoptosis and
      proinflammatory gene upregulation. Therefore, CS-NHS crosslinking can potentially
      provide an effective, safe, and biocompatible means of corneal reinforcement.

PMID- 28763563
TI  - A Proposed Method to Estimate In Situ Dissolved Gas Concentrations in Gas
      Saturated Groundwater.
AB  - Gas-saturated groundwater forms bubbles when brought to atmospheric pressure,
      preventing precise determination of its in situ dissolved gas concentrations. To
      overcome this problem, a modeling approach called the atmospheric sampling method
      is suggested here to recover the in situ dissolved gas concentrations of
      groundwater collected ex situ under atmospheric conditions at the Horonobe
      Underground Research Laboratory, Japan. The results from this method were
      compared with results measured at the same locations using two special
      techniques, the sealed sampler and pre-evacuated vial methods, that have been
      developed to collect groundwater under its in situ conditions. In gas-saturated
      groundwater cases, dissolved methane and inorganic carbon concentrations derived
      using the atmospheric sampling method were mostly within +/-4 and +/-10%,
      respectively, of values from the sealed sampler and pre-evacuated vial methods.
      In gas-unsaturated groundwater, however, the atmospheric sampling method
      overestimated the in situ dissolved methane concentrations, because the
      groundwater pressure at which bubbles appear (Pcritical ) was overestimated. The
      atmospheric sampling method is recommended for use where gas-saturated
      groundwater can be collected only ex situ under atmospheric conditions.

PMID- 28763564
TI  - The accuracy of static pressure measurement with water-filled urodynamic systems.
AB  - AIMS: To quantify the inaccuracy of pressure measurement by water-filled systems,
      with a view to recommending better practice. METHODS: Papers examining quality of
      measurements were reviewed, and standards documents examined. Technical data from
      manufacturers were gathered and summarized. Measurements were made on two
      different urodynamic systems. Individual inaccuracies were combined using the
      root sum of squares method. RESULTS: The total inaccuracy in measurement may
      reach up to 9.6 cmH2 O on pdet , but with good practice this may be mitigated to
      1.3 cmH2 O. CONCLUSIONS: Water-filled systems, while being the recommended method
      for urodynamic measurements, are subject to a potential inaccuracy during poor
      use of up to approximately 10 cmH2 O on pdet . Good practice can reduce this
      inaccuracy to a tolerable level, that is, approximately 1 cmH2 O.

PMID- 28763565
TI  - Resilience and Posttraumatic Stress Disorder Symptoms in National Guard Soldiers
      Deployed to Iraq: A Prospective Study of Latent Class Trajectories and Their
      Predictors.
AB  - This study examined the prospective course of posttraumatic stress disorder
      (PTSD) symptoms in a cohort of National Guard soldiers (N = 522) deployed to
      combat operations in Iraq. Participants were assessed 4 times: 1 month before
      deployment, 2-3 months after returning from deployment, 1 year later, and 2 years
      postdeployment. Growth mixture modeling revealed 3 distinct trajectories: low
      stable symptoms, resilient, 76.4%; new-onset symptoms, 14.2%; and chronic
      distress, 9.4%. Relative to the resilient class, membership in both the new-onset
      symptoms and chronic distress trajectory classes was predicted by negative
      emotionality/neuroticism, odds ratios (ORs) = 1.09, 95% CI [1.02, 1.17], and OR =
      1.22, 95% CI [1.09,1.35], respectively; and combat exposure, OR = 1.07, 95% CI
      [1.02, 1.12], and OR = 1.12, 95% CI [1.02, 1.24], respectively. Membership in the
      new-onset trajectory class was predicted by predeployment military preparedness,
      OR = 0.95, 95% CI [0.91, 0.98], perceived threat during deployment, OR = 1.07,
      95% CI [1.03, 1.10], and stressful life events following deployment, OR = 1.44,
      95% CI [1.05, 1.96]. Prior deployment to Iraq or Afghanistan, OR = 3.85, 95% CI
      [1.72, 8.69], predeployment depression, OR = 1.27, 95% CI [1.20, 1.36], and
      predeployment concerns about a deployment's impact on civilian/family life, OR =
      1.09, 95% CI [1.02, 1.16], distinguished the chronic distress group relative to
      the resilient group. Identifying predeployment vulnerability and postdeployment
      contextual factors provides insight for future efforts to bolster resilience,
      prevent, and treat posttraumatic symptoms.

PMID- 28763566
TI  - Metabolites and microbial composition of stool of women with fecal incontinence:
      Study design and methods.
AB  - AIMS: This paper aims to report the rationale, design, and the specific
      methodology of an ongoing nested observational study that will determine the
      association of the metabolite and microbial composition of stool with fecal
      incontinence (FI). METHODS: Eligible cases are participants with FI enrolled in
      the Controlling Anal Incontinence in women by Performing Anal Exercises with
      Biofeedback or Loperamide (CAPABLe) trial, a Pelvic Floor Disorders Network trial
      across eight clinical centers in the United States. Women of similar age without
      FI in the last year served as controls. All subject collected stool samples at
      the baseline and 24-week visit at home using a standardized collection method.
      Samples were shipped to and stored at centralized laboratories. RESULTS: Specimen
      collection commenced December 2014 and was completed in May 2016. Fecal water and
      DNA has been extracted and is currently being analyzed by targeted metabolic
      profiling for stool metabolites and 16S rRNA gene sequencing for stool
      microbiota. CONCLUSIONS: This article describes the rationale and design of a
      study that could provide a paradigm shift for the treatment of FI in women.

PMID- 28763567
TI  - Low-intensity extracorporeal shock wave therapy promotes myogenesis through
      PERK/ATF4 pathway.
AB  - AIM: Stress urinary incontinence (SUI) is a significant health problem for women.
      Treatments employing muscle derived stem cells (MDSCs) may be a promising
      approach to this prevalent, bothersome condition, but these treatments are
      invasive and require collection of cells from one site for injection into
      another. It is also unknown whether or not these cells establish themselves and
      function as muscle cells in the target tissues. Alternatively, low-intensity
      extracorporeal shock wave therapy (Li-ESWT) is non-invasive and has shown
      positive outcomes in the treatment of multiple musculoskeletal disorders, but the
      biological effects responsible for clinical success are not yet well understood.
      The aim of this study is to explore the possibility of employing Li-ESWT for
      activation of MDSCs in situ and to further elucidate the underlying biological
      effects and mechanisms of action in urethral muscle. METHODS: Urethral muscle
      derived stem cells (uMDSCs) were harvest from Zucker Lean (ZUC-LEAN) (ZUC-Leprfa
      186) rats and characterized with flow cytometry. Li-ESWT (0.02 mJ/mm2 , 3 Hz, 200
      pulses) and GSK2656157, an inhibitor of PERK pathway, were applied to L6 rat
      myoblast cells. To assess for myotube formation, we used immunofluorescence
      staining and western blot analysis in uMDSCs and L6 cells. RESULTS: The results
      indicate that uMDSCs could form myotubes. Myotube formation was significantly
      increased by the Li-ESWT as was the expression of muscle heavy chain (MHC) and
      myogenic factor 5 (Myf5) in L6 cells in vitro. Li-ESWT activated protein kinase
      RNA-like ER kinase (PERK) pathway by increasing the phosphorylation levels of
      PERK and eukaryotic initiation factor 2a (eIF2alpha) and by increasing activating
      transcription factor 4 (ATF4). In addition, GSK2656157, an inhibitor of PERK,
      effectively inhibited the myotube formation in L6 rat myoblast cells.
      Furthermore, GSK2656157 also attenuated myotube formation induced by Li-ESWT.
      CONCLUSION: In conclusion, this experiment reveals that rat uMDSCs can be
      isolated successfully and can form myotubes in vitro. PERK/ATF4 pathway was
      involved in myotube formation, and L6 rat myoblast cells were activated by Li
      ESWT to form myotubes. These findings suggest that PERK/ATF4 pathway is activated
      by Li-ESWT. This study elucidates one of the biochemical pathways responsible for
      the clinical improvements seen after Li-ESWT. It is possible that this
      information will help to establish Li-ESWT as an acceptable treatment modality
      and may help to further refine the use of Li-ESWT in the clinical practice of
      medicine.

PMID- 28763568
TI  - Comorbidity of Posttraumatic Stress Disorder and Depression in Tortured,
      Treatment-Seeking Refugees.
AB  - Comorbid posttraumatic stress disorder (PTSD) and depression is common in refugee
      groups; however, little is known about the predictors and correlates of
      comorbidity in treatment-seeking refugees. Participants in this study were 134
      refugees resettled in Switzerland. Most participants were from Turkey, Iran, and
      Sri Lanka, and 92.7% had been exposed to torture. Self-report measures were
      implemented to assess PTSD, depression, mental and physical health-related
      quality of life (QoL), as well as pre- and postmigration experiences. Findings
      indicated that approximately half the sample met criteria for PTSD and
      depression, 33.6% met criteria for depression only, and only 2.2% met criteria
      for PTSD only. Several variables emerged as predictors of comorbidity in contrast
      to no diagnosis: female gender, odds ratio (OR) = 0.17; age, OR = 0.93; time in
      Switzerland, OR = 1.16; and trauma exposure, OR = 1.19. Postmigration stress was
      also associated with greater likelihood of comorbidity compared with no
      diagnosis, OR = 1.32, and a single diagnosis, OR = 1.14. Further, dual diagnosis
      was associated with significantly poorer mental health-related and physical
      health-related QoL (mental health-related QoL: dual diagnosis vs. single
      diagnosis, d = -0.52 and dual diagnosis vs. no diagnosis, d = -1.30; physical
      health-related QoL: dual diagnosis vs. single diagnosis, d = -0.73 and dual
      diagnosis vs. no diagnosis: d = -1.04). Findings indicated that comorbidity was
      highly prevalent in this sample of treatment-seeking refugees and was associated
      with a substantial impairment burden. Psychological interventions for refugees
      should consider the dual impact of PTSD and depression symptoms to optimally
      decrease distress and improve QoL in this vulnerable group.

PMID- 28763569
TI  - Fragmentation patterns of 4(5)-nitroimidazole and 1-methyl-5-nitroimidazole-The
      effect of the methylation.
AB  - We present here the photofragmentation patterns of doubly ionized 4(5)
      nitroimidazole and 1-methyl-5-nitroimidazole. The doubly ionized state was
      created by core ionizing the C 1s orbitals of the samples, rapidly followed by
      Auger decay. Due to the recent development of nitroimidazole-based
      radiosensitizing drugs, core ionization was selected as it represents the very
      same processes taking place under the irradiation with medical X-rays. In
      addition to the fragmentation patterns of the sample, we study the effects of
      methylation on the fragmentation patterns of nitroimidazoles. We found that
      methylation alters the fragmentation significantly, especially the charge
      distribution between the final fragments. The most characteristic feature of the
      methylation is that it effectively quenches the production of NO and NO+ , widely
      regarded as key radicals in the chemistry of radiosensitization by the
      nitroimidazoles.

PMID- 28763570
TI  - Iron and Manganese in Groundwater: Using Kriging and GIS to Locate High
      Concentrations in Buncombe County, North Carolina.
AB  - For health, economic, and aesthetic reasons, allowable concentrations (as
      suggested by the United States Environmental Protection Agency) of the secondary
      contaminants iron (Fe) and manganese (Mn) found present in drinking water are 0.3
      and 0.05 mg/L, respectively. Water samples taken from private drinking wells in
      rural communities within Buncombe County, North Carolina contain concentrations
      of these metals that exceed secondary water quality criteria. This study
      predicted the spatial distribution of Fe and Mn in the county, and evaluated the
      effect of site environmental factors (bedrock geology, ground elevation,
      saprolite thickness, and drinking water well depth) in controlling the
      variability of Fe and Mn in groundwater. A statistically significant correlation
      between Fe and Mn concentrations, attributable to bedrock geology, was
      identified. Prediction models were created using ordinary kriging and cokriging
      interpolation techniques to estimate the presence of Fe and Mn in groundwater
      where direct measurements are not possible. This same procedure can be used to
      estimate the trend of other contaminants in the groundwater in different areas
      with similar hydrogeological settings.

PMID- 28763571
TI  - Enzymatic Synthesis of Psilocybin.
AB  - Psilocybin is the psychotropic tryptamine-derived natural product of Psilocybe
      carpophores, the so-called "magic mushrooms". Although its structure has been
      known for 60 years, the enzymatic basis of its biosynthesis has remained obscure.
      We characterized four psilocybin biosynthesis enzymes, namely i) PsiD, which
      represents a new class of fungal l-tryptophan decarboxylases, ii) PsiK, which
      catalyzes the phosphotransfer step, iii) the methyltransferase PsiM, catalyzing
      iterative N-methyl transfer as the terminal biosynthetic step, and iv) PsiH, a
      monooxygenase. In a combined PsiD/PsiK/PsiM reaction, psilocybin was synthesized
      enzymatically in a step-economic route from 4-hydroxy-l-tryptophan. Given the
      renewed pharmaceutical interest in psilocybin, our results may lay the foundation
      for its biotechnological production.

PMID- 28763572
TI  - Voronoi-Tessellated Graphite Produced by Low-Temperature Catalytic Graphitization
      from Renewable Resources.
AB  - A highly crystalline graphite powder was prepared from the low temperature (800
      1000  degrees C) graphitization of renewable hard carbon precursors using a
      magnesium catalyst. The resulting graphite particles are composed of Voronoi
      tessellated regions comprising irregular sheets; each Voronoi-tessellated region
      having a small "seed" particle located near their centroid on the surface. This
      suggests nucleated outward growth of graphitic carbon, which has not been
      previously observed. Each seed particle consists of a spheroidal graphite shell
      on the inside of which hexagonal graphite platelets are perpendicularly affixed.
      This results in a unique high surface area graphite with a high degree of
      graphitization that is made with renewable feedstocks at temperatures far below
      that conventionally used for artificial graphites.

PMID- 28763573
TI  - Parallel DNA Synthesis on Poly(ethylene terephthalate).
AB  - The fabrication of DNA arrays directly on aminolyzed sheets of poly(ethylene
      terephthalate) (PET) is described. Array surfaces typically employ bifunctional
      linkers or layers of covalently attached polymers to provide substrate hydroxy
      groups as synthesis attachment points. An amine treatment is used here to expose
      hydroxy groups on films of PET. These hydroxy groups can then be used to couple
      phosphoramidites and initiate the array synthesis without further
      functionalization steps. Arrays fabricated on these substrates with a maskless
      array synthesizer are tolerant of the high number of chemical exposure steps
      required to synthesize relatively long oligonucleotides. The results might be of
      the greatest use to the synthetic biology community, for whom a flexible and
      robust substrate could enable new strategies to enhance the throughput of
      oligonucleotide synthesis.

PMID- 28763574
TI  - Social status and housing factors affect reproductive performance of pregnant
      sows in groups.
AB  - Group-housing systems for pregnant sows are considered a welfare-promoting
      alternative to the individual stall. A major concern associated with pregnant
      sows housed in group pens is increased aggression at mixing and at feeding, which
      may cause chronic stress among some of the sows in the group due to low feed
      intake and social stress. Prolonged activation of the stress axis, based on
      elevated cortisol levels, may inhibit or impair reproductive success via
      disruption of the reproductive axis. Mixing sows into groups shortly after
      insemination evokes a stress response, which may affect fertilization and
      implantation due to sustained, elevated cortisol levels that disrupt reproductive
      processes. Yet, most studies reported minimal effects of group housing sows
      during pregnancy on reproduction or cortisol-related stress response. Differences
      between housing systems-in terms of group size, floor-space allowance, feeding
      system, and genetics-could account for these unexpected results. Indeed,
      interrupted feed intake, especially in early pregnancy, and sustained aggression
      in late pregnancy are two unfavorable social stresses that deserve special
      attention in order to achieve good reproductive performance. Unfortunately, most
      studies do not consider other factors, such as social rank and parity, which may
      interactively affect reproductive success and aggressive behavior of sows,
      especially in group-pen systems.

PMID- 28763575
TI  - Cardiac Safety of Rupatadine in a Single-Ascending-Dose and Multiple-Ascending
      Dose Study in Healthy Japanese Subjects, Using Intensive Electrocardiogram
      Assessments-Comparison With the Previous White Caucasian Thorough QT Study.
AB  - A thorough QT/QTc study in healthy white Caucasian subjects demonstrated that
      rupatadine has no proarrhythmic potential and raised no cardiac safety concerns.
      The present phase 1 study aimed to confirm the cardiac safety of rupatadine in
      healthy Japanese subjects. In this randomized, double-blind, placebo-controlled
      study, 27 healthy Japanese subjects were administered single and multiple
      escalating rupatadine doses of 10, 20, and 40 mg or placebo. Triplicate
      electrocardiogram (ECG) recordings were performed on days -1, 1, and 5 at several
      points, and time-matched pharmacokinetic samples were also collected.
      Concentration-effect analysis based on the change in the QT interval corrected
      using Fridericia's formula (QTcF) from average baseline was performed. Data from
      the formal TQT study in white Caucasian subjects was used for a comparison
      analysis. The ECG data for rupatadine at doses up to 40 mg did not show an effect
      on the QTc interval of regulatory concern. The sensitivity of this study to
      detect small changes in the QTc interval was confirmed by demonstrating a
      significant shortening of QTcF on days 1 and 5 four hours after a standardized
      meal. The data from this study exhibited no statistically significant differences
      in the QTc effect between Japanese and white Caucasian subjects.

PMID- 28763576
TI  - Methodological considerations regarding online extraction of water from soils for
      stable isotope determination.

PMID- 28763577
TI  - Bioreactors with hydrostatic pressures imitating physiological environments in
      intervertebral discs.
AB  - Intervertebral discs are normally exposed to a variety of loads and stresses but
      hydrostatic pressure (HP) could be the main biosignal for chondrogenic cell
      differentiation and maintenance of this tissue. Although there are simple
      approaches to intermittently expose cell cultures to HP in separate material
      testing devices, utilization of biomimetic bioreactors aiming to provide in vitro
      conditions mimicking those found in vivo, attracts special attention. However,
      design of such bioreactors is complex due to the requirement of high HP
      magnitudes (up to 3 MPa) applied in different regimes mimicking pressures arising
      in intervertebral disc during normal daily activities. Furthermore, efficient
      mass transfer has to be facilitated to cells within 3D scaffolds, and the
      engineering challenges include avoidance or removal of gas bubbles in the culture
      medium before pressurization as well as selection of appropriate, biocompatible
      construction materials and maintenance of sterility during cultivation. Here, we
      review approaches to induce HP in 2D and 3D cell cultures categorized into 5
      groups: (I) discontinuous systems with direct pressurization of the cultivation
      medium by a piston, (II) discontinuous systems with indirect pressurization by a
      compression fluid, (III) continuous systems with direct pressurization of the
      cultivation medium, static culture, (IV) continuous systems with culture
      perfusion, and (V) systems applying HP in conjunction with other physical
      signals. Although the complexity is increasing as additional features are added
      to the systems, the need to understand HP effects on cells and tissues in a
      physiologically relevant, yet precisely controlled, environment together with
      current technological advancements are leading towards innovative bioreactor
      solutions.

PMID- 28763578
TI  - Symmetry-Directed Self-Assembly of a Tetrahedral Protein Cage Mediated by de Novo
      Designed Coiled Coils.
AB  - The organization of proteins into new hierarchical forms is an important
      challenge in synthetic biology. However, engineering new interactions between
      protein subunits is technically challenging and typically requires extensive
      redesign of protein-protein interfaces. We have developed a conceptually simple
      approach, based on symmetry principles, that uses short coiled-coil domains to
      assemble proteins into higher-order structures. Here, we demonstrate the assembly
      of a trimeric enzyme into a well-defined tetrahedral cage. This was achieved by
      genetically fusing a trimeric coiled-coil domain to its C terminus through a
      flexible polyglycine linker sequence. The linker length and coiled-coil strength
      were the only parameters that needed to be optimized to obtain a high yield of
      correctly assembled protein cages.

PMID- 28763579
TI  - Sleeping above the enemy: Sleeping site choice by black-fronted titi monkeys
      (Callicebus nigrifrons).
AB  - The costs imposed by predation may result in behavioral adaptations to reduce
      mortality risk, including the choice and use of sleeping sites. The threat of
      predation, however, is rarely the sole force shaping sleeping site choice, which
      is likely to reflect other factors such as foraging needs as well. Here we
      describe the use of sleeping sites by three groups of small Neotropical monkeys,
      the black-fronted titi monkeys (Callicebus nigrifrons), and evaluate the role of
      predation pressure and foraging optimization in their choice of sleeping sites.
      We monitored each group for 9-20 months at two Atlantic Forest sites in
      southeastern Brazil. The titi monkeys used taller and larger trees to sleep than
      the average trees at each study site and chose branches with high vegetation
      coverage and located in higher forest strata than those used during diurnal
      activity. Sleeping sites were randomly distributed within each group's home
      range, and the groups avoided using the same site on consecutive nights. The
      characteristics of the sleeping sites and the behavior of the titi monkeys
      suggest that predation avoidance, especially of scansorial carnivores, is an
      important factor driving sleeping site choice. We conclude that titi monkeys'
      strategy to avoid predation while sleeping depends on the presence of a
      heterogeneous forest stratum with large emergent trees and liana tangles, which
      offer a physical barrier against predators.

PMID- 28763580
TI  - Enhancement of bone regeneration with the accordion technique via HIF-1alpha/VEGF
      activation in a rat distraction osteogenesis model.
AB  - Axial micromotion of bone fragments promotes callus formation and bone healing
      during the process of distraction osteogenesis (DO). This study investigated the
      effects of the combined axial compression and distraction (accordion) technique
      on bone regeneration in rat DO model. Male Sprague-Dawley rats (n = 62) underwent
      right tibial transverse osteotomy and were randomly divided into four groups
      after lengthening: control (no manipulation) and three experimental groups
      assigned on the basis of the period of accordion manoeuvres in the consolidation
      phase (Groups 1, 2, and 3 with accordion technique applied at Weeks 1, 3, and 5,
      respectively). Animals were terminated at 1 week after each accordion phase
      (i.e., Weeks 2, 4, and 6). Callus formation was monitored by X-ray radiography;
      new bone quality was evaluated by microcomputed tomography, histological
      analysis, and mechanical testing. Serum levels of hypoxia-inducible factor (HIF)
      1alpha and vascular endothelial growth factor (VEGF) were measured. Callus
      formation after accordion manoeuvre at Week 3 (Group 2) increased significantly
      over time of consolidation. The microcomputed tomography and mechanical analysis
      revealed Group 2 had more newly formed bone and superior mechanical properties in
      contrast to the other groups at termination. Histomorphological and
      immunohistochemical analyses confirmed a greater degree of osteogenesis and
      angiogenesis corresponding to increased serum levels of HIF-1alpha and VEGF in
      Group 2. The accordion technique was effective in promoting bone consolidation
      via activation of HIF-1alpha/VEGF during DO. The accordion technique may be used
      in the middle phase of bone consolidation to promote bone formation in patients
      undergoing DO treatment.

PMID- 28763581
TI  - Surfactant-Assisted Phase-Selective Synthesis of New Cobalt MOFs and Their
      Efficient Electrocatalytic Hydrogen Evolution Reaction.
AB  - Reported herein are two new polymorphic Co-MOFs (CTGU-5 and -6) that can be
      selectively crystallized into the pure 2D or 3D net using an anionic or neutral
      surfactant, respectively. Each polymorph contains a H2 O molecule, but differs
      dramatically in its bonding to the framework, which in turn affects the crystal
      structure and electrocatalytic performance for hydrogen evolution reaction (HER).
      Both experimental and computational studies find that 2D CTGU-5 which has
      coordinates water and more open access to the cobalt site has higher
      electrocatalytic activity than CTGU-6 with the lattice water. The integration
      with co-catalysts, such as acetylene black (AB) leads to a composite material,
      AB&CTGU-5 (1:4) with very efficient HER catalytic properties among reported MOFs.
      It exhibits superior HER properties including a very positive onset potential of
      18 mV, low Tafel slope of 45 mV dec-1 , higher exchange current density of 8.6*10
      4  A cm-2 , and long-term stability.

PMID- 28763582
TI  - Fifty years of continuous precipitation and stream chemistry data from the
      Hubbard Brook ecosystem study (1963-2013).
AB  - The Hubbard Brook Ecosystem Study officially began on 1 June 1963. This archive
      contains the results of 50 yr of collection and analysis of (at least) weekly
      stream water and precipitation samples obtained during the period 1963-2014 (from
      1 June 1963 to 30 May 2013). Stream chemistry for the nine gauged watersheds and
      precipitation chemistry for precipitation gauges distributed throughout the
      Hubbard Brook Experimental Forest are reported as concentrations in (mg/L).

PMID- 28763583
TI  - Model for the Functional Active State of the TS Ribozyme from Molecular
      Simulation.
AB  - Recently, a crystal structure has been reported of a new catalytic RNA, the TS
      ribozyme, that has been identified through comparative genomics and is believed
      to be a metalloribozyme having novel mechanistic features. Although this data
      provides invaluable structural information, analysis suggests a conformational
      change is required to arrive at a catalytically relevant state. We report results
      of molecular simulations that predict a spontaneous local rearrangement of the
      active site, leading to solution structures consistent with available functional
      data and providing competing mechanistic hypotheses that can be experimentally
      tested. The two competing hypotheses differ in the proposed identity of the
      catalytic general acid: either a water molecule coordinating a Mg2+ ion bound at
      the Watson-Crick edge of residue C7, or the N3 position of residue C7 itself.

PMID- 28763585
TI  - 44. Jahrestagung der ADF in Gottingen.

PMID- 28763584
TI  - S2k Guidelines for the diagnosis and treatment of chronic pruritus - update -
      short version.
AB  - Associated with a host of different diseases, pruritus is a cardinal symptom that
      poses an interdisciplinary diagnostic and therapeutic challenge. Over time, that
      symptom may progress independently of the initial cause, thus losing its function
      as a warning sign and turning into a clinically relevant disease of its own. In
      Germany, approximately 13.5 % of the general population are affected by chronic
      pruritus, with an incidence of 7 %. All forms of chronic pruritus require
      targeted treatment consisting of (a) diagnosis and management of the underlying
      disease, (b) dermatological treatment of primary or secondary (for example, dry
      skin, scratch lesions) symptoms, (c) symptomatic antipruritic treatment, and (d)
      psychological/psychotherapeutic treatment in case of an underlying or associated
      psychological or psychosomatic condition. Medical care of patients with chronic
      pruritus should therefore include an interdisciplinary approach, in particular
      with respect to diagnosis and therapy of the underlying disease as well as in
      terms of the management of treatment and adverse events. The objective of the
      present interdisciplinary guidelines is to define and standardize diagnostic and
      therapeutic procedures in patients with chronic pruritus. This is a short version
      of the current S2 guidelines on chronic pruritus. The long version may be found
      at www.awmf.org.

PMID- 28763586
TI  - Als Melanommetastase diagnostizierter Riesenzelltumor: Sondengefuhrte Operation
      einer mittels PET/CT identifizierten Lasion.

PMID- 28763587
TI  - Asymptomatic erythematous-violaceous scrotal vesicles in a 78-year-old man.

PMID- 28763588
TI  - Ein solitarer rotlicher Knoten am oberen Rucken einer Frau mittleren Alters.

PMID- 28763589
TI  - Wissenschaftspreis der Berliner Stiftung fur Dermatologie.

PMID- 28763590
TI  - Tue Gutes und rede daruber!

PMID- 28763591
TI  - Der anulare atrophische Lichen ruber planus: eine seltene klinische Entitat.

PMID- 28763593
TI  - Asymptomatische erythematos-livide skrotale Vesiculae bei einem 78-jahrigen
      Patienten.

PMID- 28763594
TI  - Forschung zu Genodermatosen durch neue Genom-Editing-Methoden.

PMID- 28763596
TI  - Kongresskalender 2017.

PMID- 28763595
TI  - Psychosocial distress and desire for support among inpatients with skin cancer.
AB  - BACKGROUND: Regular assessment of psychosocial distress is an important component
      of adequate psycho-oncological and social support in cancer patients. To date,
      relevant studies on skin cancer patients have primarily included individuals with
      melanoma. OBJECTIVES: (1) Does the need for psychosocial support vary with the
      type of skin cancer? (2) Do mentally distressed patients desire support? (3) From
      the various individuals in the treatment team, whom do patients choose as
      potential contact person? PATIENTS UND METHODS: Inpatients with skin cancer were
      asked to self-assess their psychosocial situation using the Hornheide
      questionnaire. In addition, they were asked about their desire for psychosocial
      support and the preferred potential contact person. RESULTS: The need for support
      among the 116 patients surveyed varied significantly depending on the diagnosis
      (p = 0.007). However, the direct comparison between patients with melanoma (n =
      38; 32.8 %) and squamous cell carcinoma (n = 9; 7.8 %) (p = 0.724) or other types
      of skin cancer (n = 20; 17.2 %) (p = 0.366) revealed no such difference. The
      prevalence of psychosocial distress (n = 49; 42.2 %) and the desire for support
      (n = 20; 17.4 %) showed considerable differences. Patients primarily chose a
      physician (n = 14/35) or a psychologist (n = 13/35) as potential "go-to" person
      for their mental distress. CONCLUSIONS: Apart from psychosocial distress, the
      desire for support should be assessed, and patients should be provided access to
      additional psychosocial care options. With respect to the need for psychosocial
      support, it does not seem to be justified to preferentially - or even exclusively
      - consider melanoma patients in clinical practice and research.

PMID- 28763597
TI  - Dermales Melanom in grobetaem kongenitalen, plaqueartigen blauen Naevus.

PMID- 28763598
TI  - Dermatoskopie bei Papillomatosis confluens et reticularis (Gougerot-Carteaud
      Syndrom).

PMID- 28763599
TI  - Erythematose Plaques in der vulvo-perinealen Region: Die diagnostische Bedeutung
      der Dermatoskopie.

PMID- 28763600
TI  - Lepra - Ein Uberblick uber Klinik, Diagnose und Therapie.

PMID- 28763601
TI  - Leprosy - an overview of clinical features, diagnosis, and treatment.
AB  - Leprosy is a chronic infectious disease caused by Mycobacterium (M.) leprae.
      Worldwide, 210,758 new cases were diagnosed in 2015. The highest incidence is
      found in India, Brazil, and Indonesia. While the exact route of transmission
      remains unknown, nasal droplet infection is thought to be most likely. The
      pathogen primarily affects the skin and peripheral nervous system. The disease
      course is determined by individual host immunity. Clinically, multibacillary
      lepromatous variants are distinguished from paucibacillary tuberculoid forms.
      Apart from the various characteristic skin lesions, the condition is marked by
      damage to the peripheral nervous system. Advanced disease is characterized by
      disfiguring mutilations. Current treatment options are based on WHO
      recommendations. Early treatment frequently results in complete remission without
      sequelae. While paucibacillary forms are treated with rifampicin and dapsone for
      at least six months, multibacillary leprosy is treated for at least twelve
      months, additionally requiring clofazimine. Leprosy reactions during therapy may
      considerably aggravate the disease course. Besides individual treatment, WHO
      supported preventive measures and strategies play a key role in endemic areas.

PMID- 28763602
TI  - Stationare Hauttumorpatienten - Psychosoziale Belastung und Unterstutzungswunsch.

PMID- 28763603
TI  - Preistrager der OGDV Fibroblasten-Heterogenitat in der Hautkrebsentstehung.

PMID- 28763604
TI  - Pruriginose follikulare Porokeratose.

PMID- 28763606
TI  - Ausschreibung der Deutschen Stiftung Allergie - Klaus-Kalveram-Preis.

PMID- 28763605
TI  - Primary cutaneous aspergillosis - an uncommon opportunistic infection Review of
      the literature and case presentation.

PMID- 28763607
TI  - Primar kutane Aspergillose - eine seltene opportunistische Infektion Ein
      Fallbericht mit Literaturubersicht.

PMID- 28763608
TI  - S2k-Leitlinie zur Diagnostik und Therapie des chronischen Pruritus - Update -
      Kurzversion.

PMID- 28763609
TI  - Erythema exsudativum multiforme als Impfkomplikation (Folge eines
      Arbeitsunfalles).

PMID- 28763610
TI  - Bone regeneration by means of a three-dimensional printed scaffold in a rat
      cranial defect.
AB  - Recently, computer-designed three-dimensional (3D) printing techniques have
      emerged as an active research area with almost unlimited possibilities. In this
      study, we used a computer-designed 3D scaffold to drive new bone formation in a
      bone defect. Poly-L-lactide (PLLA) and bioactive beta-tricalcium phosphate (TCP)
      were simply mixed to prepare ink. PLLA + TCP showed good printability from the
      micronozzle and solidification within few seconds, indicating that it was indeed
      printable ink for layer-by-layer printing. In the images, TCP on the surface of
      (and/or inside) PLLA in the printed PLLA + TCP scaffold looked dispersed. MG-63
      cells (human osteoblastoma) adhered to and proliferated well on the printed PLLA
      + TCP scaffold. To assess new bone formation in vivo, the printed PLLA + TCP
      scaffold was implanted into a full-thickness cranial bone defect in rats. The new
      bone formation was monitored by microcomputed tomography and histological
      analysis of the in vivo PLLA + TCP scaffold with or without MG-63 cells. The bone
      defect was gradually spontaneously replaced with new bone tissues when we used
      both bioactive TCP and MG-63 cells in the PLLA scaffold. Bone formation driven by
      the PLLA + TCP30 scaffold with MG-63 cells was significantly greater than that in
      other experimental groups. Furthermore, the PLLA + TCP scaffold gradually
      degraded and matched well the extent of the gradual new bone formation on
      microcomputed tomography. In conclusion, the printed PLLA + TCP scaffold
      effectively supports new bone formation in a cranial bone defect.

PMID- 28763611
TI  - Triplet Separation Drives Singlet Fission after Femtosecond Correlated Triplet
      Pair Production in Rubrene.
AB  - Singlet fission, a multistep molecular process in which one photon generates two
      triplet excitons, holds great technological promise. Here, by applying a
      combination of transient transmittance and two-dimensional electronic
      spectroscopy with 5 fs laser pulses, we resolve the full set of fission steps
      before the onset of spin dephasing. In addition to its role as a viable singlet
      fission material, single-crystalline rubrene is selected because its energetics
      and transition dipole alignment uniquely allow for the unambiguous identification
      of the various fission steps through their contributions to distinct
      spectroscopic features. The measurements reveal that the neighboring correlated
      triplet pair achieves its maximum population within 20 fs. Subsequent growth of
      the triplet signal on picosecond time scales is attributable to spatial
      separation of the triplets, proceeding nonadiabatically through weakly coupled
      but near-resonant states. As such, we provide evidence in crystalline rubrene for
      a singlet fission step that, until now, has not been convincingly observed.

PMID- 28763612
TI  - Cyclic Peptoids as Mycotoxin Mimics: An Exploration of Their Structural and
      Biological Properties.
AB  - Cyclic peptoids have recently emerged as important examples of peptidomimetics
      for their interesting complexing properties and innate ability to permeate
      biological barriers. In the present contribution, experimental and theoretical
      data evidence the intricate conformational and stereochemical properties of five
      novel hexameric peptoids decorated with N-isopropyl, N-isobutyl, and N-benzyl
      substituents. Complexation studies by NMR, in the presence of sodium tetrakis[3,5
      bis(trifluoromethyl)phenyl]borate (NaTFPB), theoretical calculations, and single
      crystal X-ray analyses indicate that the conformationally stable host/guest metal
      adducts display architectural ordering comparable to that of the enniatins and
      beauvericin mycotoxins. Similarly to the natural depsipeptides, the synthetic
      oligolactam analogues show a correlation between ion transport abilities in
      artificial liposomes and cytotoxic activity on human cancer cell lines. The
      reported results demonstrate that the versatile cyclic peptoid scaffold, for its
      remarkable conformational and complexing properties, can morphologically mimic
      related natural products and elicit powerful biological activities.

PMID- 28763613
TI  - The Importance of Mitophagy in Maintaining Mitochondrial Function in U373MG
      Cells. Bafilomycin A1 Restores Aminochrome-Induced Mitochondrial Damage.
AB  - Aminochrome, an orthoquinone formed during the dopamine oxidation of
      neuromelanin, is neurotoxic because it induces mitochondria dysfunction, protein
      degradation dysfunction (both autophagy and proteasomal systems), alpha-synuclein
      aggregation to neurotoxic oligomers, neuroinflammation, and oxidative and
      endoplasmic reticulum stress. In this study, we investigated the relationship
      between aminochrome-induced autophagy/lysosome dysfunction and mitochondrial
      dysfunction in U373MGsiGST6 cells. Aminochrome (75 MUM) induces mitochondrial
      dysfunction as determined by (i) a significant decrease in ATP levels (70%; P <
      0.001) and (ii) a significant decrease in mitochondrial membrane potential (P <
      0.001). Interestingly, the pretreatment of U373MGsiGST6 cells with 100 nM
      bafilomycin-A1, an inhibitor of lysosomal vacuolar-type H+-ATPase, restores ATP
      levels, mitochondrial membrane potential, and mitophagy, and decreases cell
      death. These results reveal (i) the importance of macroautophagy/the lysosomal
      degradation system for the normal functioning of mitochondria and for cell
      survival, and (ii) aminochrome-induced lysosomal dysfunction depends on the
      aminochrome-dependent inactivation of the vacuolar-type H+-ATPase, which pumps
      protons into the lysosomes. This study also supports the proposed protective role
      of glutathione transferase mu2-2 (GSTM2) in astrocytes against aminochrome
      toxicity, mediated by mitochondrial and lysosomal dysfunction.

PMID- 28763614
TI  - Development of Novel Peptide-Based Michael Acceptors Targeting Rhodesain and
      Falcipain-2 for the Treatment of Neglected Tropical Diseases (NTDs).
AB  - This paper describes the development of a class of peptide-based inhibitors as
      novel antitrypanosomal and antimalarial agents. The inhibitors are based on a
      characteristic peptide sequence for the inhibition of the cysteine proteases
      rhodesain of Trypanosoma brucei rhodesiense and falcipain-2 of Plasmodium
      falciparum. We exploited the reactivity of novel unsaturated electrophilic
      functions such as vinyl-sulfones, -ketones, -esters, and -nitriles. The Michael
      acceptors inhibited both rhodesain and falcipain-2, at nanomolar and micromolar
      levels, respectively. In particular, the vinyl ketone 3b has emerged as a potent
      rhodesain inhibitor (k2nd = 67 * 106 M-1 min-1), endowed with a picomolar binding
      affinity (Ki = 38 pM), coupled with a single-digit micromolar activity against
      Trypanosoma brucei brucei (EC50 = 2.97 MUM), thus being considered as a novel
      lead compound for the discovery of novel effective antitrypanosomal agents.

PMID- 28763615
TI  - Out-of-Plane Electromechanical Response of Monolayer Molybdenum Disulfide
      Measured by Piezoresponse Force Microscopy.
AB  - Two-dimensional (2D) materials have recently been theoretically predicted and
      experimentally confirmed to exhibit electromechanical coupling. Specifically,
      monolayer and few-layer molybdenum disulfide (MoS2) have been measured to be
      piezoelectric within the plane of their atoms. This work demonstrates and
      quantifies a nonzero out-of-plane electromechanical response of monolayer MoS2
      and discusses its possible origins. A piezoresponse force microscope was used to
      measure the out-of-plane deformation of monolayer MoS2 on Au/Si and Al2O3/Si
      substrates. Using a vectorial background subtraction technique, we estimate the
      effective out-of-plane piezoelectric coefficient, d33eff, for monolayer MoS2 to
      be 1.03 +/- 0.22 pm/V when measured on the Au/Si substrate and 1.35 +/- 0.24 pm/V
      when measured on Al2O3/Si. This is on the same order as the in-plane coefficient
      d11 reported for monolayer MoS2. Interpreting the out-of-plane response as a
      flexoelectric response, the effective flexoelectric coefficient, MUeff*, is
      estimated to be 0.10 nC/m. Analysis has ruled out the possibility of elastic and
      electrostatic forces contributing to the measured electromechanical response. X
      ray photoelectron spectroscopy detected some contaminants on both MoS2 and its
      substrate, but the background subtraction technique is expected to remove major
      contributions from the unwanted contaminants. These measurements provide evidence
      that monolayer MoS2 exhibits an out-of-plane electromechanical response and our
      analysis offers estimates of the effective piezoelectric and flexoelectric
      coefficients.

PMID- 28763616
TI  - Highly Efficient Flexible Quantum Dot Solar Cells with Improved Electron
      Extraction Using MgZnO Nanocrystals.
AB  - Colloidal quantum dot (CQD) solar cells have high potential for realizing an
      efficient and lightweight energy supply for flexible or wearable electronic
      devices. To achieve highly efficient and flexible CQD solar cells, the electron
      transport layer (ETL), extracting electrons from the CQD solid layer, needs to be
      processed at a low-temperature and should also suppress interfacial
      recombination. Herein, a highly stable MgZnO nanocrystal (MZO-NC) layer is
      reported for efficient flexible PbS CQD solar cells. Solar cells fabricated with
      MZO-NC ETL give a high power conversion efficiency (PCE) of 10.4% and 9.4%, on
      glass and flexible plastic substrates, respectively. The reported flexible CQD
      solar cell has the record efficiency to date of flexible CQD solar cells.
      Detailed theoretical simulations and extensive characterizations reveal that the
      MZO-NCs significantly enhance charge extraction from CQD solids and diminish the
      charge accumulation at the ETL/CQD interface, suppressing charge interfacial
      recombination. These important results suggest that the low-temperature processed
      MZO-NCs are very promising for use in efficient flexible solar cells or other
      flexible optoelectronic devices.

PMID- 28763617
TI  - Direct Laser Writing of delta- to alpha-Phase Transformation in Formamidinium
      Lead Iodide.
AB  - Organolead halide perovskites are increasingly considered for applications well
      beyond photovoltaics, for example, as the active regions within photonic devices.
      Herein, we report the direct laser writing (DLW: 458 nm cw-laser) of the
      formamidinium lead iodide (FAPbI3) yellow delta-phase into its high-temperature
      luminescent black alpha-phase, a remarkably easy and scalable approach that takes
      advantage of the material's susceptibility to transition under ambient
      conditions. Through the DLW of alpha-FAPbI3 tracks on delta-FAPbI3 single-crystal
      surfaces, the controlled and rapid microfabrication of highly luminescent
      structures exhibiting long-term phase stability is detailed, offering an avenue
      toward the prototyping of complex perovskite-based optical devices. The dynamics
      and kinetics of laser-induced delta- to alpha-phase transformations are
      investigated in situ by Raman microprobe analysis, as a function of irradiation
      power, time, temperature, and atmospheric conditions, revealing an interesting
      connection between oxygen intercalation at the surface and the delta- to alpha
      phase transformation dynamics, an insight that will find application within the
      wider context of FAPbI3 thermal phase relations.

PMID- 28763618
TI  - Mechanistic Studies of Hafnium-Pyridyl Amido-Catalyzed 1-Octene Polymerization
      and Chain Transfer Using Quench-Labeling Methods.
AB  - Chromophore quench-labeling applied to 1-octene polymerization as catalyzed by
      hafnium-pyridyl amido precursors enables quantification of the amount of active
      catalyst and observation of the molecular weight distribution (MWD) of Hf-bound
      polymers via UV-GPC analysis. Comparison of the UV-detected MWD with the MWD of
      the "bulk" (all polymers, from RI-GPC analysis) provides important mechanistic
      information. The time evolution of the dual-detection GPC data, concentration of
      active catalyst, and monomer consumption suggests optimal activation conditions
      for the Hf pre-catalyst in the presence of the activator [Ph3C][B(C6F5)4]. The
      chromophore quench-labeling agents do not react with the chain-transfer agent
      ZnEt2 under the reaction conditions. Thus, Hf-bound polymeryls are selectively
      labeled in the presence of zinc-polymeryls. Quench-labeling studies in the
      presence of ZnEt2 reveal that ZnEt2 does not influence the rate of propagation at
      the Hf center, and chain transfer of Hf-bound polymers to ZnEt2 is fast and quasi
      irreversible. The quench-label techniques represent a means to study commercial
      polymerization catalysts that operate with high efficiency at low catalyst
      concentrations without the need for specialized equipment.

PMID- 28763619
TI  - Chirality-Driven Parallel and Antiparallel beta-Sheet Secondary Structures of Phe
      Ala Lipodipeptides.
AB  - Four Phe-Ala lipodipeptides with different stereochemical structures are observed
      to self-assemble into twisted nanoribbons in water. The handedness of the twisted
      nanoribbons is controlled by the chirality of the phenylalanine near the alkyl
      chain, while the stacking handedness of the phenyl and carbonyl groups is
      determined by the alanine at the C-terminal. The homochiral and heterochiral
      lipodipeptides self-assemble into parallel and antiparallel beta-sheet
      structures, respectively. The 1H NMR, FTIR, X-ray diffraction, and circular
      dichroism characterizations indicate that these phenomena are mainly driven by
      the interaction between neighboring phenyl groups and H-bonding among the amide
      groups.

PMID- 28763620
TI  - Acute effects of exercise intensity on subsequent substrate utilisation,
      appetite, and energy balance in men and women.
AB  - Exercise is capable of influencing the regulation of energy balance by acutely
      modulating appetite and energy intake coupled to effects on substrate
      utilization. Yet, few studies have examined acute effects of exercise intensity
      on aspects of both energy intake and energy metabolism, independently of energy
      cost of exercise. Furthermore, little is known as to the gender differences of
      these effects. One hour after a standardised breakfast, 40 (19 female), healthy
      participants (BMI 23.6 +/- 3.6 kg.m-2, VO2peak 34.4 +/- 6.8 mL.kg-1.min-1)
      undertook either high-intensity intermittent cycling (HIIC) consisting of 8
      repeated 60 s bouts of cycling at 95% VO2peak or low-intensity continuous cycling
      (LICC), equivalent to 50% VO2peak, matched for energy cost (~950 kJ) followed by
      90 mins of rest, in a randomised crossover design. Throughout each study visit,
      satiety was assessed subjectively using visual analogue scales alongside blood
      metabolites and GLP-1. Energy expenditure and substrate utilization were measured
      over 75 min postexercise via indirect calorimetry. Energy intake was assessed for
      48 h postintervention. No differences in appetite, GLP-1, or energy intakes were
      observed between HIIC and LICC, with or without stratifying for gender.
      Significant differences in postexercise nonesterified fatty acid concentrations
      were observed between intensities in both genders, coupled to a significantly
      lower respiratory exchange ratio following HIIC (P = 0.0028), with a trend
      towards greater reductions in respiratory exchange ratioin males (P = 0.079). In
      conclusion, high-intensity exercise, if energy matched, does not lead to greater
      appetite or energy intake, but may exert additional beneficial metabolic effects
      that may be more pronounced in males.

PMID- 28763621
TI  - Age-related testosterone declines can be detected in men's fingernails.
AB  - Testosterone plays multiple roles in the regulation of development, physiology,
      reproduction, and behavior. Age-related testosterone declines are expected in the
      population. However, measuring circulating testosterone is especially challenging
      because concentrations are labile, responding to social situations and
      challenges. Matrices that integrate long-term testosterone levels are therefore
      valuable as biomarkers of endogenous levels as well as chronic exposures. Here,
      we report on a simple method to extract and measure accumulated testosterone from
      human fingernails using commercial enzyme immunoassay kits. Furthermore, we
      demonstrate known human testosterone sex and age trends. Our method is especially
      useful for quantifying testosterone in men's nails, where a small amount of
      matrix is required. Thus, this approach is a potential tool for biomonitoring
      endogenous as well as exogenous testosterone exposure. We suggest considering
      nails as an alternative matrix for quantifying other steroids as well.

PMID- 28763622
TI  - Label-Free, LC-MS-Based Assays to Quantitate Small-Molecule Antagonist Binding to
      the Mammalian BLT1 Receptor.
AB  - We have developed and validated label-free, liquid chromatography-mass
      spectrometry (LC-MS)-based equilibrium direct and competition binding assays to
      quantitate small-molecule antagonist binding to recombinant human and mouse BLT1
      receptors expressed in HEK 293 cell membranes. Procedurally, these binding assays
      involve (1) equilibration of the BLT1 receptor and probe ligand, with or without
      a competitor; (2) vacuum filtration through cationic glass fiber filters to
      separate receptor-bound from free probe ligand; and (3) LC-MS analysis in
      selected reaction monitoring mode for bound probe ligand quantitation. Two novel,
      optimized probe ligands, compounds 1 and 2, were identified by screening 20
      unlabeled BLT1 antagonists for direct binding. Saturation direct binding studies
      confirmed the high affinity, and dissociation studies established the rapid
      binding kinetics of probe ligands 1 and 2. Competition binding assays were
      established using both probe ligands, and the affinities of structurally diverse
      BLT1 antagonists were measured. Both binding assay formats can be executed with
      high specificity and sensitivity and moderate throughput (96-well plate format)
      using these approaches. This highly versatile, label-free method for studying
      ligand binding to membrane-associated receptors should find broad application as
      an alternative to traditional methods using labeled ligands.

PMID- 28763623
TI  - The Effects of Anterolateral Tenodesis on Tibiofemoral Contact Pressures and
      Kinematics.
AB  - BACKGROUND: Anterolateral tenodeses are increasingly popular in combination with
      intra-articular anterior cruciate ligament reconstructions. Despite the
      perception of risk of overconstraint and lateral osteoarthritis, evidence is
      lacking regarding the effect of graft tensioning on knee kinematics and intra
      articular compartmental joint pressures. PURPOSE: To investigate tibiofemoral
      joint contact pressures and kinematics related to an anterolateral lesion and the
      effectiveness of a MacIntosh tenodesis in restoring these when varying (1) graft
      tension and (2) tibial rotation during graft fixation. STUDY DESIGN: Controlled
      laboratory study. METHODS: Eight fresh-frozen cadaveric knees were tested in a
      customized rig with femur fixed and tibia free to move from 0 degrees  to 90
      degrees  of flexion. The quadriceps and iliotibial band were loaded by means of a
      weighted pulley system. At 30 degrees  intervals of knee flexion, tibiofemoral
      contact pressures were measured with a Tekscan sensor and tibiofemoral kinematics
      were recorded by use of an optical tracking system. The knee was tested intact
      and then with an anterolateral soft tissue transection. MacIntosh tenodeses were
      then tested in a randomized order with 20 N or 80 N of graft tension, each with
      the tibia held in neutral intact alignment or free to rotate. RESULTS: Tibial
      anterior translation and internal rotation were significantly increased and
      lateral contact pressures significantly reduced compared with the intact knee
      following anterolateral soft tissue cutting ( P < .05). Contact pressures were
      restored with fixed neutral tibial rotation combined with 20 N or 80 N of graft
      tension or by a free-hanging tibia with 20 N of graft tension (all P values >
      .5). Grafts tensioned with 80 N caused significant overconstraint both when the
      tibia was fixed and free hanging (all P values < .05). Increases in the lateral
      tibiofemoral contact pressures were also seen when the tibia was free hanging and
      80 N was used for graft tension ( P < .05). CONCLUSION: Anterolateral soft tissue
      injury caused reduced lateral tibiofemoral contact pressures and altered
      tibiofemoral kinematics; these were restored with a MacIntosh procedure performed
      with 20 N of graft tension. If 80 N of graft tension was used, increased lateral
      contact pressures and overconstraint in internal rotation were seen. With the
      tibia free hanging, intact contact biomechanics were restored when 20 N of graft
      tension was applied, but 80 N of graft tension significantly increased lateral
      tibiofemoral pressures and overconstrained internal rotation. The kinematic and
      contact pressure effects were significantly correlated: Changes in tibial
      rotation caused by increased graft tension correlated with elevated lateral
      articular contact pressure. CLINICAL RELEVANCE: Controlling tibial position
      appears important when tensioning anterolateral tenodeses. However, the
      identified changes were subtle and may not be clinically significant in a fully
      loaded knee.

PMID- 28763624
TI  - Comparative transcriptomic analysis of porcine peripheral blood reveals
      differentially expressed genes from the cytokine-cytokine receptor interaction
      pathway related to health status.
AB  - While some research has looked into the host genetic response in pigs challenged
      with specific viruses or bacteria, few studies have explored the expression
      changes of transcripts in the peripheral blood of sick pigs that may be infected
      with multiple pathogens on farms. In this study, the architecture of the
      peripheral blood transcriptome of 64 Duroc sired commercial pigs, including 18
      healthy animals at entry to a growing facility (set as a control) and 23 pairs of
      samples from healthy and sick pen mates, was generated using RNA-Seq technology.
      In total, 246 differentially expressed genes were identified to be specific to
      the sick animals. Functional enrichment analysis for those genes revealed that
      the over-represented gene ontology terms for the biological processes category
      were exclusively immune activity related. The cytokine-cytokine receptor
      interaction pathway was significantly enriched. Nine functional genes from this
      pathway encoding members (as well as their receptors) of the interleukins,
      chemokines, tumor necrosis factors, colony stimulating factors, activins, and
      interferons exhibited significant transcriptional alteration in sick animals. Our
      results suggest a subset of novel marker genes that may be useful candidate genes
      in the evaluation and prediction of health status in pigs under commercial
      production conditions.

PMID- 28763625
TI  - MicroRNA-1-3p inhibits the proliferation and migration of oral squamous cell
      carcinoma cells by targeting DKK1.
AB  - We investigated the functional role and mechanism of miR-1-3p and DKK1 in oral
      squamous cell carcinoma (OSCC) cells. The level of miR-1-3p and DKK1 expression
      were detected in OSCC tissues and cells using reverse-transcription -
      quantitative PCR and Western blot. A dual luciferase reporter gene assay was
      applied to confirm the targeting relationship between miR-1-3p and DKK1.
      Functional assays, including MTT, Transwell, colony formation, and flow cytometry
      analysis were conducted to verify their effect on cell progressions. MTT, colony
      formation, and Transwell assays indicated that the proliferation, migration, and
      invasion of SCC-4 cells was impaired with high miR-1-3p expression but promoted
      with high DKK1 expression. The results from cell cycle analysis and annexin-V-PI
      assays for apoptosis suggested that miR-1-3p suppressed the transit of SCC-4
      cells from G0/G1 to S and induced apoptosis. In summary, miR-1-3p suppressed the
      progression of OSCC by inhibiting DKK1 expression.

PMID- 28763626
TI  - Virtual Morris task responses in individuals in an abstinence phase from alcohol.
AB  - The present study was aimed at examining spatial learning and memory, in 33 men
      and 12 women with alcohol use disorder (AUD) undergoing ethanol detoxification,
      by using a virtual Morris task. As controls, we recruited 29 men and 10 women
      among episodic drinkers without a history of alcohol addiction or alcohol-related
      diseases. Elevated latency to the first movement in all trials was observed only
      in AUD persons; furthermore, control women had longer latencies compared with
      control men. Increased time spent to reach the hidden platform in the learning
      phase was found for women of both groups compared with men, in particular during
      trial 3. As predicted, AUD persons (more evident in men) spent less time in the
      target quadrant during the probe trial; however, AUD women had longer latencies
      to reach the platform in the visible condition during trials 6 and 7 that
      resulted in a greater distance moved. As for the probe trial, men of both groups
      showed increased virtual locomotion compared with the women of both groups. The
      present investigation confirms and extends previous studies showing (i) different
      gender responses in spatial learning tasks, (ii) some alterations due to alcohol
      addiction in virtual spatial learning, and (iii) differences between AUD men and
      AUD women in spatial-behaviour-related paradigms.

PMID- 28763627
TI  - Limb remote ischemia per-conditioning protects the heart against ischemia
      reperfusion injury through the opioid system in rats.
AB  - Remote ischemia per-conditioning (RPerC) has been demonstrated to have cardiac
      protection, but the underlying mechanism remains unclear. This study aimed to
      investigate the mechanism underlying cardiac protection of RPerC. Adult male
      Sprague-Dawley rats were used in this study. Cardiac ischemia/reperfusion (I/R)
      was induced by 30 min of occlusion and 3 h of reperfusion of the left anterior
      descending coronary artery. RPerC were performed by 5 min of occlusion of the
      right femoral artery followed by 5 min of reperfusion for three times during
      cardiac ischemia. The hemodynamics, left ventricular function, arrhythmia, and
      infarct area were measured. Protein expression levels of endothelial nitric oxide
      synthase (eNOS), inducible NOS (iNOS), protein kinase C-epsilon (PKCepsilon), and
      PKCdelta in the myocardium were assayed. During I/R, systolic artery pressure and
      left ventricular function were decreased, infarct area was increased, and
      arrhythmia score was increased (P < 0.05). However, changes of the above
      parameters were significantly attenuated in RPerC-treated rats compared with
      control rats (P < 0.05). The cardiac protective effects of RPerC were prevented
      by naloxone or glibenclamide. Also, RPerC increased the protein expression levels
      of eNOS, iNOS, PKCepsilon, and PKCdelta in the myocardium compared with control
      rats. These effects were blocked by naloxone, an opioid receptor antagonist, and
      glibenclamide, an ATP-sensitive K+ channel blocker (KATP). In summary, this study
      suggests that RPerC protects the heart against I/R injury through activation of
      opioid receptors and the NO-PKC-KATP channel signaling pathways.

PMID- 28763629
TI  - The contribution of p53 and Y chromosome long arm genes to regulation of
      apoptosis in mouse testis.
AB  - Apoptosis of excessive or defective germ cells is a natural process occurring in
      mammalian testes. Tumour suppressor protein p53 is involved in this process both
      in developing and adult male gonads. Its contribution to testicular physiology is
      known to be modified by genetic background. The aim of this study was to evaluate
      the combined influence of the p53 and Y chromosome long arm genes on male germ
      cell apoptosis. Knockout of the transformation related protein 53 (Trp53) gene
      was introduced into congenic strains: B10.BR (intact Y chromosome) and B10.BR
      Ydel (Y chromosome with a deletion in the long arm). The level of apoptosis in
      the testes of 19-day-old and 3-month-old male mice was determined using the
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ
      nick-end labelling (TUNEL) method. The study revealed that although p53 is
      involved in germ cell apoptosis in peripubertal testes, this process can also be
      mediated by p53-independent mechanisms. However, activation of p53-independent
      apoptotic pathways in the absence of the p53 protein requires engagement of the
      multicopy Yq genes and was not observed in gonads of B10.BR-Ydel-p53-/- males.
      The role of Yq genes in the regulation of testicular apoptosis seems to be
      restricted to the initial wave of spermatogenesis and is not evident in adult
      gonads. The study confirmed, instead, that p53 does participate in spontaneous
      apoptosis in mature testes.

PMID- 28763628
TI  - The value of 18F-FDG PET/CT imaging in breast cancer staging.
AB  - The National Comprehensive Cancer Network (NCCN) guidelines recommend assessment
      with positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose
      integrated with computed tomography (18F-FDG PET/CT) in staging of breast cancer,
      starting from the stage IIIA. Previously, PET/CT contributed to the accurate
      staging from the stage IIB. Our aim is to evaluate the contribution of 18F-FDG
      PET/CT in staging of breast cancer patients. A total of 234 patients were
      retrospectively evaluated. PET/CT was performed preoperatively in 114/234 and
      postoperatively in 120/234 patients. Initial staging was performed based on
      histopathological results in 125/234 and clinical results in 109/234 patients,
      according to the American Joint Committee on Cancer (AJCC) classification. All
      patients had a normal abdominal ultrasound and chest x-ray. Following PET/CT
      imaging, modification in the staging was performed in patients with the
      metastatic findings. In 42/234 (17.9%) patients hypermetabolic extra-axillary
      regional lymph nodes and in 65/234 patients (27.7%) distant metastatic
      involvement were detected with PET/CT. Modification in the staging was applied in
      82/234 (35%) patients. Patient management was changed in 69/234 (29.4%) cases.
      The percentage of patients with upstaging, according to each stage, was as
      follows: IIA: 18.6%, IIB: 30%, IIIA: 46.3%, IIIB: 68.8%, and IIIC: 20.8%. In
      43/43 patients, 99mTc-methylene diphosphonate (MDP) bone scan did not show
      additional bone metastasis. In 5/32 patients, metastatic involvement was detected
      with sentinel lymph node biopsy (SLNB), but preoperative PET/CT scan did not
      reveal hypermetabolic lymph nodes. Although our study was limited by the referral
      bias and lack of homogeneity in the referral group, PET/CT still significantly
      contributed to the accurate staging and management of our breast cancer patients,
      starting from the stage IIA.

PMID- 28763630
TI  - Growth of hollow cell spheroids in microbead templated chambers.
AB  - Cells form hollow, spheroidal structures during the development of many tissues,
      including the ocular lens, inner ear, and many glands. Therefore, techniques for
      in vitro formation of hollow spheroids are valued for studying developmental and
      disease processes. Current in vitro methods require cells to self-organize into
      hollow morphologies; we explored an alternative strategy based on cell growth in
      predefined, spherical scaffolds. Our method uses sacrificial, gelatin microbeads
      to simultaneously template spherical chambers within a hydrogel and deliver cells
      into the chambers. We use mouse lens epithelial cells to demonstrate that cells
      can populate the internal surfaces of the chambers within a week to create
      numerous hollow spheroids. The platform supports manipulation of matrix
      mechanics, curvature, and biochemical composition to mimic in vivo
      microenvironments. It also provides a starting point for engineering organoids of
      tissues that develop from hollow spheroids.

PMID- 28763631
TI  - An ultra-effective method of generating extramultipotent cells from human
      fibroblasts by ultrasound.
AB  - Multipotent cells have similar basic features of all stem cells but limitation in
      ability of self-renewal and differentiation compared with pluripotent cells.
      Here, we have developed an ultra effective, gene- and chemical-free method of
      generating extra multipotent (xpotent) cells which have differentiation potential
      more than limited cell types, by the mechanism of ultrasound-directed permeation
      of environmental transition-guided cellular reprogramming (Entr). Ultrasound
      stimulus generated a massive number of Entr-mediated xpotent (x/Entr) spheroids
      from human dermal fibroblasts (HDFs) 6 days after treatment. The emergence of
      x/Entr was first initiated by the introduction of human embryonic stem cell (ESC)
      environments into the HDFs to start fast cellular reprogramming including
      activation of stress-related kinase signaling pathways, subsequent chromatin
      remodeling, and expression of pluripotent-related genes via transient membrane
      damage caused by ultrasound-induced cavitation. And then, pluripotent markers
      were transported into their adjacent HDFs via direct cell-to-cell connections in
      order to generate xpotent clusters. The features of x/Entr cells were
      intermediate between pluripotency and multipotency in terms of pluripotency with
      three germ layer markers, multi-lineage differentiation potential, and no
      teratoma formation. This physical stimulus-mediated reprogramming strategy was
      cost-effective, simple, quick, produced significant yields, and was safe, and can
      therefore provide a new paradigm for clinical application.

PMID- 28763632
TI  - NiS and MoS2 nanosheet co-modified graphitic C3N4 ternary heterostructure for
      high efficient visible light photodegradation of antibiotic.
AB  - The development of efficient solar driven catalytic system for the degradation of
      antibiotics has become increasingly important in environmental protection and
      remediation. Non-noble-metal NiS and MoS2 nanosheet co-modified graphitic C3N4
      ternary heterostructure has been synthesized via a facile combination of
      hydrothermal and ultrasound method, and the ternary heterostructure has been
      utilized for photocatalytic degradation of antibiotic agents. The antibiotics of
      ciprofloxacin (CIP) and tetracycline hydrochloride (TC) were photodegraded by the
      hybrid under the visible light. The optimal photodegradation rate of the ternary
      heterostructure reaches about 96% after 2h irradiation, which is 2.1 times higher
      than that of pure g-C3N4 for TC degradation. The photocatalytic degradation rates
      of the ternary heterostructure for both CIP and TC obey the pseudo-first-order
      kinetic model. The enhanced visible light adsorption and charge separation
      efficiency contribute to the photocatalytic performance of the ternary
      heterostructure. This work provides new insights and pathways by which efficient
      degradation of antibiotics can be achieved and will stimulate further studies in
      this important field.

PMID- 28763633
TI  - Application of water@silica core-shell particles for suppressing gasoline pool
      fires.
AB  - A new type of dry powders with capsular structure was fabricated for fire
      suppression, in which the content of water approached 60%. The capsules with the
      size of 3-5MUm consisted of liquid core and solid shell, where the core was water
      droplet and the shell was assembled silicon dioxide particles with surface
      hydrophobic modification. The shell of close-packed silica particles surrounding
      each water droplet provided the structural rigidity of the capsules and enabled
      their application as powder fire suppressants. Two different scaled real fire
      tests showed that thus-prepared solid powders could extinguish 0.21MW gasoline
      pool fire in 2.0s with agent mass of 0.055kg, and 1.0MW gasoline pool fire in
      5.0s with agent mass of 0.49kg. Such fire extinguishing performance greatly
      outperformed the conventional monoammonium phosphate (ABC) powders, neat silica
      powders and water mist, with significantly reduced fire extinguishing time and
      mass of agent consumed. Mechanism of the core-shell particles in fire suppression
      was discussed based on established theories and experimental results.

PMID- 28763634
TI  - Impact of delayed insemination on pregnancy rates to gender selected semen in a
      fixed-time AI system.
AB  - The objectives of the current experiment were to determine if delaying
      insemination by 8 h in a FTAI protocol would alter estrus expression and
      pregnancy rates in cows inseminated with sex-sorted semen, characterize bull
      variation in pregnancy rates to sex-sorted semen and examine the impact of
      repeated years of FTAI to sex-sorted semen on calving distribution. Over three
      breeding seasons, postpartum cows (n = 839) were estrous synchronized using the 5
      day CO-Synch + CIDR system. Cows were given GnRH (100 MUg i.m., Factrel) at time
      of insertion of a controlled internal drug releasing device (CIDR; Eazi-Breed
      CIDR). Five d later CIDR was removed and PGF2alpha (25 mg i.m., Lutalyse) was
      given at removal and 8 h later. Estrus detection aids were applied at CIDR
      removal. Cows were inseminated with X-sorted or Y-sorted sex-sorted semen at 72 h
      (NORM) or 80 h (DELAY) after CIDR removal, and GnRH was administered at AI. At
      insemination, estrus status was categorized as positive (YES), partial (QUES),
      unknown (NR) or negative (NO). Bulls were introduced to cows at 14 d and removed
      at 60 d after FTAI. Pregnancy diagnosis was performed by ultrasound at d 60 after
      FTAI and via palpation at 60 d after bull removal. There was no difference (P >
      0.05) in pregnancy rates to sex-sorted semen or final pregnancy rates between
      NORM and DELAY cows. Pregnancy to sex-sorted semen averaged 35.2% whereas final
      pregnancy rates were 90.6%. More cows (P < 0.05) in the DELAY group expressed
      estrus before FTAI, but this increase did not alter pregnancy rates to sex-sorted
      semen. Expression of estrus before FTAI increased (P < 0.02) pregnancy rates to
      sex-sorted semen across treatments with differences being YES > QUES or NR > NO.
      There was considerable variation in pregnancy rate by bull (P < 0.05) with
      pregnancy rates ranging from 55.6% to 19.3%. Whole herd calving distribution was
      altered (P < 0.05) after 3 y of use of sex-sorted semen compared to the previous
      3 y when conventional semen was used. We conclude that delaying insemination by 8
      h in an FTAI protocol did not improve pregnancy rates to sex-sorted semen despite
      more cows exhibiting estrus before FTAI. In addition, a high bull to bull
      variation in pregnancy rates to sex-sorted semen is a limitation in FTAI systems.
      Further research into FTAI strategies for use with sex-sorted semen is warranted.

PMID- 28763635
TI  - Effect of corrosion inhibitor benzotriazole on the uptake and translocation of Cd
      in rice (Oryza sativa L.) under different exposure conditions.
AB  - Emerging contaminants that can complex with heavy metals might affect the
      speciation of coexisting metals and result in different ecological risks. As a
      widely used metal corrosion inhibitor, 1H-benzotriazole (BTR) is frequently
      detected in the environments, sometimes at very high levels. In this study, rice
      (Oryza sativa L.) was used to assess the ecological risk of combined exposure to
      cadmium (Cd) and BTR in plants and discuss the potential effects of exposure
      sequence on the uptake and translocation of Cd under hydroponic culture. In the
      combined exposure treatments, Cd concentration in rice significantly decreased
      when the molar ratio of BTR to Cd exceeded 1, while the oxidative damage of root
      was alleviated. In the sequential exposure treatments, an exposure to BTR
      accelerated the release of preabsorbed Cd from seedlings to the environment and
      increased the transport of Cd from the roots to shoots at high BTR
      concentrations. This demonstrates that the combined pollution effect of Cd and
      BTR is present not only in the environment but also in plants. With the decrease
      in Cd concentration in the roots, the electrolytic leakages from the roots also
      decreased, indicating that root damage repair was induced by the subsequent BTR
      exposure. BTR was mainly accumulated in the seedling roots. Preabsorbed BTR
      significantly increased Cd concentration in the roots of rice seedlings but
      inhibited Cd translocation from the roots to shoots of the rice seedlings.

PMID- 28763636
TI  - Importance of lithology in defining natural background concentrations of Cr, Cu,
      Ni, Pb and Zn in sedimentary soils, northeastern Brazil.
AB  - The sedimentary basins of Reconcavo and Tucano, Bahia, represent the most
      important Brazilian Phanerozoic continental basin system, formed during
      fracturing of Gondwana. The northern basin of Tucano has a semiarid climate (Bsh)
      while the southern basin of Reconcavo has a tropical rainforest climate (Af). The
      aim of this study was to determine the distribution of trace metals in soils
      derived from various sedimentary rocks and climates. Soils were collected at 30
      sites in 5 geological units at 0-20 cm and 60-80 cm deep under native vegetation.
      Physical and chemical attributes (particle size distribution, pH, Al,
      exchangeable bases, organic matter) were determined, as well as the pseudo-total
      concentrations (EPA 3050 b) and the total concentrations (X-ray fluorescence) of
      Cr, Cu, Ni, Pb and Zn. The concentrations of metals were overall correlated to
      soil texture, according to lithologic origin. Shales resulted in Vertisols 30.4
      (Zn), 27.2 (Ni), 16.9 (Cu), 7.5 (Cr) and 2.5 (Pb) times more concentrated than
      Arenosols derived from the sandstones. High Cr and Ni values in clay soils from
      shales were attributed to diffuse contamination by erosion of mafic rocks of the
      Greenstone Belt River Itapicuru (from 3 km northwest of the study area) during
      the late Jurassic. Tropical rainforest climate resulted in a slight enrichment of
      Pb and Cr, and Ni had the higher mobility during soil formation (enrichment
      factor up to 6.01). In conclusion, the geological environment is a much more
      controlling factor than pedogenesis in the concentration of metals in sedimentary
      soils.

PMID- 28763637
TI  - Sodium fluoride adversely affects ovarian development and reproduction in
      Drosophila melanogaster.
AB  - The study demonstrates the effects of chronic sub-lethal exposure of sodium
      fluoride (NaF) on reproductive structure and function of female Drosophila
      melanogaster. As a part of treatment, flies were maintained in food supplemented
      with sub-lethal concentrations of NaF (10-100 MUg/mL). Fecundity, ovarian
      morphology, presence and profusion of viable cells from ovary and fat body were
      taken into consideration for evaluating changes in reproductive homeostasis. Wing
      length (a factor demonstrating body size and reproductive fitness) was also
      monitored after NaF exposure. Significant reduction in fecundity, alteration in
      ovarian morphology along with an increase in apoptosis was observed in treated
      females. Simultaneous decline in viable cell number and larval weight validates
      the result of MTT assay. Furthermore, altered ovarian Glucose-6-phosphate
      dehydrogenase and catalase activities together with increased rate of lipid
      peroxidation after 20 and 40 MUg/mL NaF exposure confirmed the changes in
      reproduction related metabolism. Enhanced lipid peroxidation known for ROS
      generation might have induced genotoxicity which is confirmed through Comet
      assay. The enzyme activities were not dose dependent, rather manifested a bimodal
      response, which suggests a well-knit interaction among the players inducing
      stress and the ones that help establish physiological homeostasis.

PMID- 28763639
TI  - Surface pattern by nanoimprint for membrane fouling mitigation: Design,
      performance and mechanisms.
AB  - Imparting water treatment membrane with surface pattern by nanoimprint offered a
      novel approach to fouling resistance. We employed nanoimprint to fabricate line
      shape nanostructure on membrane distillation (MD) membrane surface. Patterned MD
      membrane exhibited strong antifouling property to Bovine Serum Albumin (BSA)
      protein during MD separation. Water flux decline and protein deposition were
      substantially minimized on the patterned MD membrane in comparison with the
      pristine one. Such lower fouling propensity on the patterned MD membrane was
      mainly driven by the weak hydrophobic interaction between BSA protein and
      patterned MD membrane surface. Weaker adhesion force mapping of the patterned MD
      membrane was quantified. Representative force-distance curve of pristine MD
      membrane showed a strong attractive depletion force comparing with that of
      patterned one. The simple, chemical-free, and scalable nanofabrication approach
      enables varying designs on membrane surface for special membrane properties.

PMID- 28763638
TI  - A systematic review of growth curve mixture modelling literature investigating
      trajectories of perinatal depressive symptoms and associated risk factors.
AB  - BACKGROUND: The aim of this study was to review the growth curve mixture
      modelling (GCMM) literature investigating trajectories of perinatal maternal
      depressive symptoms and associated risk factors. METHODS: A systematic search of
      peer-reviewed articles published until November 2015 was conducted in seven
      databases. Articles using GCMM to identify trajectories of perinatal depressive
      symptoms were considered. Symptoms had to be assessed at least three times,
      anytime from pregnancy to two years postpartum (PROSPERO; 2016:CRD42016032600).
      RESULTS: Eleven studies met inclusion criteria. All reported a low risk
      trajectory, characterised by stable low depressive symptoms throughout the
      perinatal period. A stable moderate-high or high symptom trajectory was reported
      in eight of 11 studies, suggesting a high-risk group with persistent depressive
      symptoms. Six studies also reported transient trajectories, with either
      increasing, decreasing or episodic depressive symptoms. None of the demographic,
      personality or clinical characteristics investigated systematically
      differentiated groups of women with different symptom trajectories, within or
      across studies. Thus, it is difficult to differentiate women at high or low risk
      of specific perinatal depression trajectories. LIMITATIONS: A meta-analysis was
      not possible. The studies' settings and inclusion criteria limit the
      generalisability of the findings to low-risk, middle- to high-income women.
      CONCLUSIONS: Relatively similar trajectories of perinatal depressive symptoms
      were identified across studies. Evidence on factors differentiating women
      assigned to different trajectories was inconsistent. Research with larger samples
      and in more diverse settings is needed to inform services and policies on how and
      when to effectively identify subgroups of women at high risk of perinatal
      depression.

PMID- 28763640
TI  - Transformation and fate of natural estrogens and their conjugates in wastewater
      treatment plants: Influence of operational parameters and removal pathways.
AB  - Natural estrogens (NEs) discharged from wastewater treatment plants (WWTPs) have
      drawn great attention because of their potential risks to aquatic ecosystems.
      However, neglect of the conjugated natural estrogens (C-NEs) has caused large
      discrepancies among different studies on the removal of NEs in WWTPs. The present
      work investigated the transformation and fate of three NEs and six corresponding
      C-NEs along wastewater treatment processes. The removal efficiencies of the
      target estrogens (i.e., NEs and C-NEs) and their correlations with the
      operational parameters were determined over a twelve-month monitoring period at a
      typical WWTP adopting a combined bio-treatment process (i.e.,
      anaerobic/anoxic/oxic process followed by a moving-bed biofilm reactor). The
      concentration variations of the target estrogens along the treatment processes
      were examined to differentiate the transformation and fate of NEs and C-NEs.
      Moreover, lab-scale experiments were conducted to clarify the removal pathways of
      C-NEs in the bio-treatment process. Results indicate that both NEs and C-NEs
      could pass through the treatment processes, thus being frequently detected in the
      effluent and excess sludge. The aqueous removal efficiencies of NEs and C-NEs
      were significantly correlated with the sludge retention time and temperature,
      respectively. C-NEs were more persistent than NEs, so considerably high
      conjugated ratios (13.5-100.0%) were detected in the effluent. Sulfate conjugates
      presented a lower adsorption affinity to sludge and a slower hydrolysis rate than
      glucuronide conjugates, which makes the former more recalcitrant to
      biodegradation. This study highlights the challenge on the elimination of NEs,
      particularly their conjugates, by wastewater treatment processes.

PMID- 28763641
TI  - Degradation of natural organic matter by UV/chlorine oxidation: Molecular
      decomposition, formation of oxidation byproducts and cytotoxicity.
AB  - The degradation of natural organic matters (NOMs) by the combination of UV and
      chlorine (UV/chlorine) was investigated in this study. UV/chlorine oxidation can
      effectively degrade NOMs, with the degradation of chromophores (~80%) and
      fluorophores (76.4-80.8%) being more efficient than that of DOC (15.1-18.6%).
      This effect was attributed to the chromophores and fluorophores (double bonds,
      aromatic groups and phenolic groups) being preferentially degraded by UV/chlorine
      oxidation, particularly reactive groups with high electron donating capacity.
      Radical species *OH and *Cl were generated during UV/chlorine oxidation, with the
      contribution of *OH 1.4 times as high as that of *Cl. The degradation kinetics of
      different molecular weight (MW) fractions suggests that UV/chlorine oxidation
      degrades high MW fractions into low MW fractions, with the degradation rates of
      high MW fractions (>3000 Da) 4.5 times of those of medium MW fractions (1000-3000
      Da). In comparison with chlorination alone, UV/chlorine oxidation did not
      increase the formation (30 min) and formation potential (24 h) of
      trihalomethanes, but instead promoted the formation and formation potential of
      haloacetic acids and chloral hydrate. Adsorbable organic halogen (AOX) formed
      from UV/chlorine oxidation of NOM were 0.8 times higher than those formed from
      chlorination. Cytotoxicity studies indicated that the cytotoxicity of NOM
      increased after both chlorination and UV/chlorine oxidation, which may be due to
      the formation of AOX.

PMID- 28763642
TI  - Fate of antibiotic resistance genes and their associations with bacterial
      community in livestock breeding wastewater and its receiving river water.
AB  - Large amounts of antibiotics are currently used in livestock breeding, which is
      the main driving factor contributing to the occurrence, spread and proliferation
      of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in
      the environment. In this study, high-throughput sequencing based metagenomic
      approaches were employed to characterize the tempo-spacial changes of antibiotic
      resistome, bacterial community and their correlations in pig farming wastewater
      and its receiving river. A total of 194 ARG subtypes within 14 ARG types were
      detectable in all the samples, and their total relative abundance increased in
      the river water after receiving wastewater discharge, while decreased in the
      downstream river water. Network analysis showed that 25.26% ARGs within the same
      type or among the different types showed higher incidences of non-random co
      occurrence. The wastewater discharge evidently increased bacterial diversity and
      induced bacterial community shift in the receiving river water. The genera of
      Treponema, Prevotella, Pseudomonas, Bacteroides, Oscillibacter and Acholeplasma
      dominated in the wastewater samples and almost disappeared in the receiving river
      water, but bacterial pathogens Clostridium difficile and Arcobacter butzleri
      still occurred in the receiving water. Correlation analysis and host analysis
      consistently showed that the changes in the abundances of several key genera like
      Prevotella and Treponema were significantly and positively correlated with the
      antibiotic resistome alteration. Variation partitioning analysis indicated that
      bacterial community played a more important role in the resistome alteration than
      mobile genetic elements. This study may help to understand the correlations among
      antibiotic resistome, microbiota and environmental conditions in the wastewater
      receiving river water.

PMID- 28763644
TI  - Norepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and
      insight into the structure-activity relationships of its analogues as
      antiplasmodial agents.
AB  - Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum
      syncarpum (Rutaceae) exhibited promising antiplasmodial activities against
      Plasmodium falciparum with reported IC50 values of 2.04 MUM (D6 clone), 3.06 MUM
      (W2 clone) and observed by us 3.90 MUM (3D7 clone) and 2.56 MUM (K1 clone). In
      continuation of our work on naturally occurring antimalarial compounds, synthesis
      of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric
      dihydroxylation as a key step has been accomplished. In order to study structure
      activity-relationship (SAR) in detail, a library of 55 compounds (3-57), which
      are analogues/homologues of syncarpamide 1 were synthesized by varying the
      substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or
      by varying the acid groups in the ester and/or amide side chain based on the
      natural product lead molecule and further assayed in vitro against 3D7 and K1
      strains of P. falciparum to evaluate their antiplasmodial activities. In order to
      study the effect of position of functional groups on antiplasmodial activity
      profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it
      turned out to be inactive against both the strains. Two compounds, (S)-41 and its
      enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed
      better antiplasmodial activity with IC50 values of 3.16, 2.28 MUM (3D7) and 1.78,
      2.07 MUM (K1), respectively than the natural product, syncarpamide 1. Three
      compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC50
      values of 6.39, 6.82, 6.41 MUM against 3D7 strain, 4.27, 7.26, 2.71 MUM against
      K1 strain and with CC50 values of 147.72, 153.0, >200 MUM respectively. The in
      vitro antiplasmodial activity data of synthesized library suggests that the
      electron density and possibility of resonance in both the ester and amide side
      chains increases the antiplasmodial activity as compared to the parent natural
      product 1. The natural product syncarpamide 1 and four analogues/homologues out
      of the synthesized library of 55, (S)-41, (R)-42, (S)-55 and (S)-57 were assayed
      in vivo assay against chloroquine-resistant P. yoelii (N-67) strain of
      Plasmodium. However, none of the five molecules, 1, (S)-41, (R)-42, (S)-55 and
      (S)-57 exhibited any promising in vivo antimalarial activity against P. yoelii (N
      67) strain. Compounds 4, 6, 7 and 11 showed high cytotoxicities with CC50 values
      of 5.87, 5.08, 6.44 and 14.04 MUM, respectively. Compound 6 was found to be the
      most cytotoxic as compared to the standard drug, podophyllotoxin whereas
      compounds 4 and 7 showed comparable cytotoxicities to podophyllotoxin.

PMID- 28763643
TI  - Discovery of 5,6-diaryl-1,2,4-triazines hybrids as potential apoptosis inducers.
AB  - A series of 5,6-diaryl-1,2,4-triazines hybrids bearing a 1,2,3-triazole linker
      were synthesized by molecular hybridization strategy and evaluated for
      antiproliferative activity against three selected cancer cell lines (MGC-803, EC
      109 and PC-3). The first structure-activity relationship (SAR) for these 5,6
      diaryl-1,2,4-triazines is explored in this report with evaluation of 15 variants
      of the structural class. Among these chemical derivatives, 3-(((1-(4
      fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5,6-diphenyl-1,2,4-triazine
      (11E) showed the more potent inhibitory effect against three cell lines than 5
      Fu. Cellular mechanism studies in MGC-803 cells elucidated 11E inhibited colony
      formation and arrested cell cycle at G2/M phase. Furthermore, compound 11E caused
      morphological changes, decreased mitochondrial membrane potential, and induced
      apoptosis through the apoptosis-related proteins in MGC-803 cells. It was the
      first time, to our knowledge, that 5,6-diaryl-1,2,4-triazines bearing a 1,2,3
      triazole linker were used as potential apoptosis inducers.

PMID- 28763645
TI  - The antitrypanosomal and antitubercular activity of some
      nitro(triazole/imidazole)-based aromatic amines.
AB  - A limited number of novel 3-nitrotriazole- and 2-nitroimidazole-linked quinolines
      and quinazolines were synthesized and screened for in vitro antitrypanosomal and
      antitubercular activities as well as cytotoxicity in normal cells. All compounds
      were active against T. cruzi amastigotes, while all but one were active or
      moderately active against T. b. rhodesiense. However, only two chloroquinolines
      exhibited satisfactory selectivity indices (SI) against T. cruzi and only one of
      them demonstrated a satisfactory SI against T. b. rhodesiense. All tested
      compounds demonstrated a Minimum Inhibitory Concentration (MIC) >= 200 MUM
      against aerobic Mtb. However, the 2-nitroimidazole-based analogs were active
      against hypoxic Mtb with MIC values 2.89-9.18 MUM. The present data support our
      previous observations that 2-nitroimidazole-based aromatic amines are selectively
      active against nonreplicating Mtb, while 3-nitrotriazole-based aromatic amines
      are potent antichagasic agents.

PMID- 28763646
TI  - Design, synthesis and biological evaluation of 4-anilinoquinoline derivatives as
      novel potent tubulin depolymerization agents.
AB  - A series of novel 4-anilinoquinoline derivatives were synthesized and evaluated
      for their antiproliferative activities. Among them, 14h exhibited the most potent
      cytotoxic activity with IC50 values ranging from 1.5 to 3.9 nM against all tested
      cancer cell lines, and showed promising efficacy in multidrug resistant cancer
      cells. Flow cytometry assay, immune-fluorescence staining, microtubule dynamics
      assays and competition assays with EBI identified that 14h was a novel tubulin
      depolymerization agent by binding to the colchicine site. Importantly, in vivo
      efficacy evaluation of HCT116 xenograft model, 14h showed efficient antitumor
      activity without significant loss in body weight. All the results indicated that
      14h could be a promising candidate for the treatment of cancer.

PMID- 28763647
TI  - Discovery of 9H-purins as potential tubulin polymerization inhibitors: Synthesis,
      biological evaluation and structure-activity relationships.
AB  - Two series of N-(4-methoxyphenyl)-N-methyl-9H-purin-6-amines (9a-d and 10a-h) and
      9-substituted benzyl-6-chloro-9H-purines (11a-h) were designed and synthesized.
      Their antiproliferative activities against human myelogenous leukemia (K562),
      human neuroblastoma (SH-SY5Y) and gastric cancer (AGS) cell lines were evaluated
      using the MTT assay. The preliminary results indicated that compounds 9d and 11e
      h displayed low-micromole GI50 values against all tested cell lines. In addition,
      compounds 10b and 10d showed wonderful antiproliferative activities towards SH
      SY5Y cells with selectivity of >230-fold over K562 and AGS cells. Among them,
      compounds 9d, 10b, 10d and 11g with good antitumor activities exhibited high
      selectivity for tumor cell lines over immortalized mouse hippocampal (HT22) cell
      line. Moreover, compound 9d with sub-micromole GI50 values toward AGS cells
      exhibited moderate tubulin polymerization inhibitory activity, and induced
      apoptosis at G2/M phase arrest with a dose-dependent manner in the human AGS
      cells.

PMID- 28763648
TI  - Design, synthesis and biological evaluation of 4-amidobenzimidazole acridine
      derivatives as dual PARP and Topo inhibitors for cancer therapy.
AB  - PARP-1 could repair the DNA damages induced by Topo inhibitors, therefore
      inhibiting Topo and PARP-1 simultaneously might be able to overcome resistance
      and improve outcomes. In this study a series of 4-amidobenzimidazole acridines
      were designed and synthesized as dual Topo and PARP-1 inhibitors. Compound 11l
      displayed good inhibitory activities against Topo and PARP-1, as well as
      significantly inhibited cancer cells proliferation. Further mechanistic
      evaluations indicated that 11l treatment in MCF-7 cells induced accumulated DNA
      double-strand breaks, prompted remarkable apoptosis, and caused prominent G0/G1
      cell cycle arrest. Moreover, 11l greatly suppressed tumor growth in mice, and
      displayed favorable metabolic properties in liver microsomes. Our study suggested
      that single agents inhibiting Topo and PARP concurrently might be an alternative
      for cancer therapy and 11l represented a potential lead compound for development
      of antitumor agents.

PMID- 28763649
TI  - Biomarkers of arsenic exposure in arsenic-affected areas of the Hetao Basin,
      Inner Mongolia.
AB  - Seventy saliva samples, seventy urine samples, seventy nail samples, seventy hair
      samples, eight drinking water samples and ninety-three crop samples were
      collected from four villages of the Hetao Basin in Inner Mongolia to determine
      arsenic (As) exposure biomarkers and evaluate relationship between As uptake and
      human health risk. Trivalent As (As(III)), pentavalent As (As(V)),
      dimethylarsinic acid (DMA), arsenobetaine (AsB) and monomethylarsonic acid (MMA)
      were found in all urine samples. Only As(III) and As(V) were detected in saliva
      samples. In nail and hair samples, DMA, MMA, As(III) and As(V) were observed.
      Based on total As contents in crops and drinking water, the local residents'
      daily intake of total arsenic (TDIAs), the hazard quotient (HQ), and the cancer
      risk (R) were assessed. Male, older and cases of skin lesion participants
      generally had higher As contents in saliva, urine, nail and hair samples in
      relative to others. Salivary, urinary, nail and hair As were not significantly
      affected by body mass index (BMI) and smoking. Good correlations were observed
      between TDIAs and salivary, urinary, nail and hair As, showing that saliva,
      urine, nail and hair samples can be used as biomarkers of As exposure.
      Individually, levels of arsenicosis were positively correlated with TDIAs. The
      relationship between TDIAs and prevalence of arsenicosis concluded that, although
      As levels in crops and drinking water did not exceed national standards, they
      still pose a potential threat to human health. It was suggested that the maximum
      permissible levels of crop As and drinking water As should be re-evaluated for
      protecting human health.

PMID- 28763650
TI  - The effects of weather on pediatric seizure: A single-center retrospective study
      (2005-2015).
AB  - BACKGROUND: Several studies have reported an association between seizure and the
      weather. However, reports are conflicting. Thus, we investigated whether
      emergency department visits due to seizure are affected by weather. METHODS: We
      retrospectively analyzed 108,628 emergency department visits to Samsung Changwon
      Hospital by pediatric patients from January 2005 to December 2015. Among them,
      there were 3484 (3.2%) visits for any type of seizure. Seizures were categorized
      as febrile seizure, afebrile seizure, epilepsy, or status epilepticus. We used a
      distributed lag non-linear model with quasi-Poisson distribution to investigate
      the association between weather and pediatric seizure. RESULTS: During this 11
      year study period, over the half of total pediatric seizure patients were febrile
      seizure (53.5%) and the proportion for status epilepticus were the lowest (5.9%).
      Mean of mean temperature and diurnal temperature range were 14.7 degrees C and
      8.3 degrees C. Mean humidity was 62.1%, mean of atmospheric pressure was
      1015.5hPa and mean of sunshine was 6.3Hr. When considering the overall 0-15days
      lagged effect of weather, only mean temperature was significantly associated with
      emergency department visits. At lower temperatures, the number of emergency
      department visits increases and decreases at higher temperatures. All 4 types of
      seizure also showed similar patterns. In particular, only visits of febrile
      seizure were significantly associated with mean temperature. CONCLUSION: We
      investigated the association weather and pediatric seizure by considering 0-15day
      lags. In particular, low mean temperature increase the emergency department
      visits for pediatric seizure and high mean temperature decrease the pediatric
      seizure. In addition, only febrile seizure of 4 seizure types was affected by
      mean average temperature.

PMID- 28763651
TI  - Flame retardants on the surface of phones and personal computers.
AB  - Mobile phones and personal computers (PCs) are essential products that are
      frequently contacted in daily life. Thus, phones and computers containing flame
      retardants (FRs) may play vital roles in human exposure to FRs. We measured
      several FRs, including polybrominated diphenyl ethers (PBDEs), 1,2-bis(2,4,6
      tribromophenoxy) ethane (BTBPE), decabromodiphenyl ethane (DBDPE),
      tetrabromobisphenol (TBBPA), and phosphate flame retardants (PFRs), on the
      surfaces of phones and PCs (laptop keyboards and mice). Triphenyl phosphate
      (TPHP, 228pg/cm2) and tris(chloroisopropyl) phosphate (TCIPP, 43pg/cm2) were the
      most abundant chemicals on the surfaces of phones, while TPHP (65pg/cm2), TCIPP
      (48pg/cm2), and DBDPE (22pg/cm2) were dominant on the surfaces of PCs. The usage
      time and time after the production of the electronics were not significantly
      correlated with the FR concentrations, except for that of BDE 209. The
      concentrations of FRs differed on the surfaces of different brands of
      electronics. Dermal contact with the surface of electronics may contribute to
      human exposure to FRs, which should be of concern.

PMID- 28763652
TI  - NOx, NH3, N2O and PN real driving emissions from a Euro VI heavy-duty vehicle.
      Impact of regulatory on-road test conditions on emissions.
AB  - Euro VI emission standards for heavy-duty vehicles (HDVs) introduced for the
      first time limits for solid particle number (PN) and NH3 emissions. EU regulation
      also includes a Portable Emissions Measurement System (PEMS) based test at type
      approval, followed by in-service conformity (ISC) testing. A comprehensive study
      on the real-time on-road emissions of NOx, NH3, N2O and PN from a Euro VI HDV
      equipped with a Diesel Oxidation Catalyst (DOC), a Diesel Particle Filter (DPF),
      a Selective Catalytic Reduction (SCR) system and an Ammonia Oxidation Catalyst
      (AMOX) is presented. Our analyses revealed that up to 85% of the NOx emissions
      measured during the tests performed are not taken into consideration if the
      boundary conditions for data exclusion set in the current legislation are
      applied. Moreover, it was found that the highest NOx emissions were measured
      during urban operation. Analyses show that a large fraction urban of operation is
      not considered when 20% power threshold as boundary condition is applied. They
      also show that cold start emissions account for a large fraction of the total NOx
      emitted. Low emissions of PN (2.8*1010 to 6.5*1010#/kWh) and NH3 (1.0 to 2.2ppm)
      were obtained during the on-road tests, suggesting effectiveness of the vehicle's
      after-treatment (DPF and AMOX). Finally, a comparison between speed-based (as
      currently defined by Euro VI legislation) and land-use-based (using Geographic
      Information System (GIS)) calculation of shares of operation was performed.
      Results suggest that using GIS to categorize the shares of operation could result
      in different interpretations depending on the criteria adopted for their
      definition.

PMID- 28763653
TI  - Land use change effects on ecosystem carbon budget in the Sichuan Basin of
      Southwest China: Conversion of cropland to forest ecosystem.
AB  - In the humid subtropics, conversion of cropland to forest has been recognized to
      influence carbon cycling (e.g., soil CO2 emissions) and the associated ecosystem
      carbon balance. A three-year field study was conducted in situ to quantitatively
      evaluate effects of land use change on carbon budget in a cropland (under winter
      wheat-summer maize rotation) comparison with the adjacent forest ecosystem.
      During the three-year experimental period, on average, soil heterotrophic
      respirations were 35.19mgC.m-2.h-1 for the cropland and 40.02mgC.m-2.h-1 for the
      adjacent forest ecosystem. The quantified net primary production (NPP) were
      8724.78kgC.ha-1.year-1 for the cropland (3218.14kgC.ha-1 for winter wheat season
      and 5506.64kgC.ha-1 for summer maize season) and 6478.99kgC.ha-1.year-1 for the
      adjacent forest ecosystem. Thus, the average positive net ecosystem production
      (NEP) of 5139.33kgC.ha-1.year-1 and 2790.43kgC.ha-1.year-1 were gained in the
      cropland and the adjacent forest ecosystem, respectively. Nonetheless, if take
      into consideration of crop grain harvest (i.e., removal), the mean NEP was only
      976.69kgC.ha-1.year-1 for cropland which were over three-fold lower than for the
      adjacent forest ecosystem. The practice of conversion of cropland (maize-wheat
      rotation system) to forest consequently resulted in an average annual net carbon
      sequestration of 1813.74kgC.ha-1.year-1 in the study. Therefore, our findings
      highlight that practices of conversion of subtropical cropland to forest commonly
      conducted in the last decades act as sinks of atmospheric CO2 in southwest China.

PMID- 28763654
TI  - Evaluating the risk of phosphorus loss with a distributed watershed model
      featuring zero-order mobilization and first-order delivery.
AB  - Many semi-distributed models that simulate pollutants' losses from watersheds do
      not handle well detailed spatially distributed and temporal data with which to
      identify accurate and cost-effective strategies for controlling pollutants
      issuing from non-point sources. Such models commonly overlook the flow pathways
      of pollutants across the landscape. This work aims at closing such knowledge gap
      by developing a Spatially and Temporally Distributed Empirical model for
      Phosphorus Management (STEM-P) that simulates the daily phosphorus loss from
      source areas to receiving waters on a spatially-distributed grid-cell basis. STEM
      P bypasses the use of complex mechanistic algorithms by representing the
      phosphorus mobilization and delivery processes with zero-order mobilization and
      first-order delivery, respectively. STEM-P was applied to a 217km2 watershed with
      mixed forest and agricultural land uses situated in southwestern China. The STEM
      P simulation of phosphorus concentration at the watershed outlet approximated the
      observed data closely: the percent bias (Pbias) was -7.1%, with a Nash-Sutcliffe
      coefficient (ENS) of 0.80 on a monthly scale for the calibration period. The
      Pbias was 18.1%, with a monthly ENS equal to 0.72 for validation. The simulation
      results showed that 76% of the phosphorus load was transported with surface
      runoff, 25.2% of which came from 3.4% of the watershed area (classified as
      standard A critical source areas), and 55.3% of which originated from 17.1% of
      the watershed area (classified as standard B critical source areas). The standard
      A critical source areas were composed of 51% residences, 27% orchards, 18% dry
      fields, and 4% paddy fields. The standard B critical source areas were mainly
      paddy fields (81%). The calculated spatial and temporal patterns of phosphorus
      loss and recorded flow pathways identified with the STEM-P simulations revealed
      the field-scale critical source areas and guides the design and placement of
      effective practices for non-point source pollution control and water quality
      conservation.

PMID- 28763655
TI  - Improved source apportionment of PAHs and Pb by integrating Pb stable isotopes
      and positive matrix factorization application (PAHs): A historical record case
      study from the northern South China Sea.
AB  - To obtain the historical changes of pyrogenic sources, integrated source
      apportionment methods, which include PAH compositions, diagnostic ratios (DRs),
      Pb isotopic ratios, and positive matrix factorization (PMF) model, were developed
      and applied in sediments of the northern South China Sea. These methods provided
      a gradually clear picture of energy structural change. Spatially, Sigma15PAH
      (11.3 to 95.5ng/g) and Pb (10.2 to 74.6MUg/g) generally exhibited decreasing
      concentration gradient offshore; while the highest levels of PAHs and Pb were
      observed near the southern Taiwan Strait, which may be induced by accumulation of
      different fluvial input. Historical records of pollutants followed closely with
      the economic development of China, with fast growth of Sigma15PAH and Pb
      occurring since the 1980s and 1990s, respectively. The phasing-out of leaded
      gasoline in China was captured with a sharp decrease of Pb after the mid-1990s.
      PAHs and Pb correlated well with TOC and clay content for core sediments, which
      was not observed for surface sediments. There was an up-core increase of high
      molecular PAH proportions. Coal and biomass burning were then qualitatively
      identified as the major sources of PAHs with DRs. Furthermore, shift toward less
      radiogenic signatures of Pb isotopic ratios after 1900 revealed the start and
      growing importance of industrial sources. Finally, a greater separation and
      quantification of various input was achieved by a three-factor PMF model, which
      made it clear that biomass burning, coal combustion, and vehicle emissions
      accounted for 40+/-20%, 41+/-13%, and 19+/-12% of PAHs through the core. Biomass
      and coal combustion acted as major sources before 2000, while contributions from
      vehicle emission soared thereafter. The integrated multi-methodologies here
      improved the source apportionment by reducing biases with a step-down and cross
      validation perspective, which could be similarly applied to other aquatic
      systems.

PMID- 28763656
TI  - Assessing water scarcity in agricultural production system based on the
      generalized water resources and water footprint framework.
AB  - An indicator, agricultural water stress index (AWSI), was established based blue
      green water resources and water footprint framework for regional water scarcity
      in agricultural production industry evaluation. AWSI is defined as the ratio of
      the total agricultural water footprint (AWF) to water resources availability
      (AWR) in a single year. Then, the temporal and spatial patterns of AWSI in China
      during 1999-2014 were analyzed based on the provincial AWR and AWF
      quantification. The results show that the annual AWR in China has been maintained
      at approximately 2540Gm3, of which blue water accounted for >70%. The national
      annual AWF was approximately 1040Gm3 during the study period and comprised 65.6%
      green, 12.7% blue and 21.7% grey WFs The space difference in both the AWF for per
      unit arable land (AWFI) and its composition was significant. National AWSI was
      calculated as 0.413 and showed an increasing trend in the observed period. This
      index increased from 0.320 (mid-water stress level) in 2000 to 0.490 (high water
      stress level) in the present due to the expansion of the agricultural production
      scale. The Northern provinces, autonomous regions and municipalities (PAMs) have
      been facing high water stress, particularly the Huang-Huai-Hai Plain, which was
      at a very high water stress level (AWSI>0.800). Humid South China faces
      increasingly severe water scarcity, and most of the PAMs in the region have
      converted from low water stress level (AWSI=0.100-0.200) to mid water stress
      level (AWSI=0.200-0.400). The AWSI is more appropriate for reflecting the
      regional water scarcity than the existing water stress index (WSI) or the blue
      water scarcity (BWS) indicator, particularly for the arid agricultural production
      regions due to the revealed environmental impacts of agricultural production.
      China should guarantee the sustainable use of agricultural water resources by
      reducing its crop water footprint.

PMID- 28763657
TI  - Organochlorine pesticides in the indoor air of a theatre and museum in the Czech
      Republic: Inhalation exposure and cancer risk.
AB  - Organochlorine pesticides (OCPs) have been used to preserve the integrity of
      historical buildings or to protect collections of artefacts at potentially large
      volumes and often without detailed application records. Previous research has
      focused on the efficiency of remediation at contaminated sites (where
      identified), as well as improvement of preservation techniques and workplace
      health and safety. Few studies have assessed the human health risks from
      occupational exposure to OCPs in buildings of cultural and historical importance.
      Thus, potential risks may remain unidentified. In the present study, OCPs in
      indoor air were measured in a baroque theatre and a natural history museum in the
      Czech Republic, both of which had suspected past indoor application. In the
      theatre attic p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) levels in air were
      up to 190ngm-3, confirming past indoor use of p,p'
      dichlorodiphenyltrichloroethane (p,p'-DDT). There was also evidence of gamma
      hexachlorocyclohexane (gamma-HCH) use in the theatre (max gamma-HCH in air of
      56ngm-3). Yet, the cancer risk (CR) from occupational exposure via inhalation
      (Expi) to OCPs in the theatre was low (CR<4.0*10-6). gamma-HCH was found at
      elevated levels in air of the museum (max gamma-HCH in air of 15,000ngm-3). CR
      from Expi in the museum was moderate to high (>1*10-4). Our results show the CR
      through Expi to OCPs in buildings, such as museums can still be significant
      enough to warrant mitigation measures, e.g., remediation.

PMID- 28763658
TI  - Relationship between land-use and sources and fate of nitrate in groundwater in a
      typical recharge area of the North China Plain.
AB  - Identification of different nitrate sources in groundwater is challenging in
      areas with diverse land use and multiple potential inputs. An area with mixed
      land-uses, typical of the piedmont-plain recharge area of the North China Plain,
      was selected to investigate different nitrate sources and the impact of land use
      on nitrate distribution in groundwater. Multiple environmental tracers were
      examined, including major ions, stable isotopes of water (delta2H-H2O, delta18O
      H2O) and nitrate (delta15N-NO3- and delta18O-NO3-). Groundwater was sampled from
      four land-use types; natural vegetation (NV), farmland (FL), economic forestland
      (EF) and residential areas (RA). A mixing model using delta18O and Cl-
      concentrations showed that groundwater recharge predominantly comprises
      precipitation and lateral groundwater flow from areas of natural vegetation in
      the upper catchment, while irrigation return water and wastewater from septic
      tanks were major inputs in farmland and residential areas, respectively. Land use
      variation is the major contributing factor to different nitrate concentrations.
      In total, 80%, 49% and 86% of samples from RA, FL and EF, respectively exceeded
      the WHO standard (50mg/L NO3-), compared to 6.9% of samples from NV. Isotopes of
      delta15N-NO3- and delta18O-NO3- verified that nitrate in groundwater of the NV
      (with delta15N ranging from 1.70/00 to 4.70/00) was sourced from soil and
      precipitation. Examination of delta15N-NO3- vs delta18O-NO3- values along with
      multivariate statistical analysis (principle component and cluster analysis)
      helped identify sources with overlapping isotopic values in other land-use areas
      (where delta15N values range from 2.50/00 to 10.20/00). Manure and septic waste
      were dominant sources for most groundwater with high NO3- and Cl- concentrations
      in both farmland and residential areas. The lack of de-nitrification and fact
      that the area is a recharge zone for the North China Plain highlight the
      importance of controlling nitrate sources through careful application of manure
      and fertilizers, and control of septic leakage.

PMID- 28763659
TI  - Evaluating a Bayesian modelling approach (INLA-SPDE) for environmental mapping.
AB  - Understanding the uncertainty in spatial modelling of environmental variables is
      important because it provides the end-users with the reliability of the maps.
      Over the past decades, Bayesian statistics has been successfully used. However,
      the conventional simulation-based Markov Chain Monte Carlo (MCMC) approaches are
      often computationally intensive. In this study, the performance of a novel
      Bayesian inference approach called Integrated Nested Laplace Approximation with
      Stochastic Partial Differential Equation (INLA-SPDE) was evaluated using
      independent calibration and validation datasets of various skewed and non-skewed
      soil properties and was compared with a linear mixed model estimated by residual
      maximum likelihood (REML-LMM). It was found that INLA-SPDE was equivalent to REML
      LMM in terms of the model performance and was similarly robust with sparse
      datasets (i.e. 40-60 samples). In comparison, INLA-SPDE was able to estimate the
      posterior marginal distributions of the model parameters without extensive
      simulations. It was concluded that INLA-SPDE had the potential to map the spatial
      distribution of environmental variables along with their posterior marginal
      distributions for environmental management. Some drawbacks were identified with
      INLA-SPDE, including artefacts of model response due to the use of triangle
      meshes and a longer computational time when dealing with non-Gaussian likelihood
      families.

PMID- 28763660
TI  - Vancomycin-resistant enterococci with vanA gene in treated municipal wastewater
      and their association with human hospital strains.
AB  - Vancomycin-resistant enterococci (VRE) are pathogens of increasing medical
      importance. In Brno, Czech Republic, we collected 37 samples from the effluent of
      a wastewater treatment plant (WWTP), 21 surface swabs from hospital settings, and
      59 fecal samples from hospitalized patients and staff. Moreover, we collected 284
      gull cloacal swabs from the colony situated 35km downstream the WWTP. Samples
      were cultured selectively. Enterococci were identified using MALDI-TOF MS,
      phenotypically tested for susceptibility to antibiotics, and by PCR for
      occurrence of resistance and virulence genes. Pulsed-field gel electrophoresis
      (PFGE) and multi-locus sequence typing (MLST) were used to examine genotypic
      diversity. VRE carrying the vanA gene were found in 32 (86%, n=37) wastewater
      samples, from which we obtained 49 isolates: Enterococcus faecium (44) and
      Enterococcus gallinarum (2), Enterococcus casseliflavus (2), and Enterococcus
      raffinosus (1). From 33 (69%) of 48 inpatient stool samples, we obtained 39 vanA
      carrying VRE, which belonged to E. faecium (33 isolates), Enterococcus faecalis
      (4), and Enterococcus raffinosus (2). Nearly one-third of the samples from
      hospital surfaces contained VRE with the vanA gene. VRE were not detected among
      gulls. Sixty-seven (84%, n=80) E. faecium isolates carried virulence genes hyl
      and/or esp. Virulence of E. faecalis was encoded by gelE, asa1, and cylA genes. A
      majority of the E. faecium isolates belonged to the clinically important sequence
      types ST17 (WWTP: 10 isolates; hospital: 4 isolates), ST18 (9;8), and ST78 (5;0).
      The remaining isolates belonged to ST555 (2;0), ST262 (1;6), ST273 (3;0), ST275
      (1;0), ST549 (2;0), ST19 (0;1), ST323 (3;0), and ST884 (7;17). Clinically
      important enterococci carrying the vanA gene were almost continually detectable
      in the effluent of the WWTP, indicating insufficient removal of VRE during
      wastewater treatment and permanent shedding of these antibiotic resistant
      pathogens into the environment from this source. This represents a risk of their
      transmission to the environment.

PMID- 28763661
TI  - The mechanism and efficiency of MnO2 activated persulfate process coupled with
      electrolysis.
AB  - Pure three-dimensional manganese oxides (MnO2) were successfully synthesized by a
      simple one-step hydrothermal process. The obtained particles were characterized
      via XRD, BET, SEM, XPS and FTIR techniques. To enhance the efficiency of
      heterogeneous catalytic process, a facile and effective electrochemical method
      was introduced. The degradation of C. I. Acid Orange 7 (AO7) as the target
      pollutant in aqueous solution by an oxidation system involving MnO2 activated
      peroxydisulfate (PDS) coupled with electrochemical method is reported herein.
      Influences of some key reaction parameters such as initial pH (pH0), current
      density, initial AO7 concentration, dosage of MnO2 and anions (Cl-, NO3-, HCO3-
      and H2PO4-) were investigated. The cyclic voltammetry (CV) was performed to
      investigate the charge transfer process occurred at the surface of catalyst. LC
      MS/MS analysis was applied to identify degradation intermediates and a plausible
      degradation mechanism is proposed accordingly. Activated sludge inhibition tests
      were carried out to evaluate the change of toxicity of the dye solution in the
      oxidation process. The inorganic by-products such as NO2-, NO3-, and NH4+ along
      with AO7 degradation were also identified. The stability of MnO2 catalyst was
      evaluated by recycling experiments and the electrical energy consumption was also
      investigated. Radical quenching tests with several scavengers (methanol, tert
      butyl alcohol, 1,4-benzoquinone and phenol) were performed to clarify the
      dominating reactive species participating in this oxidation process and the
      underlying mechanisms involving the generation of radical from the proposed
      electro-assisted heterogeneous activated PDS system were identified.

PMID- 28763662
TI  - Effects of hexaconazole application on soil microbes community and nitrogen
      transformations in paddy soils.
AB  - The ecological risks of widely used hexaconazole on soil microbes remain obscure.
      Thus, a 3-month-long experiment using two typical paddy soils in China (red soil
      and black soil) was conducted to assess the effects of hexaconazole (0.6 (T1) and
      6 (T10) mgkg-1 soil) on the overall microbial biomass, respiratory activity,
      bacterial abundance and community structure, and nitrogen transformations. Soil
      was sampled after 7, 15, 30, 60, and 90days of incubation. The half-lives of the
      two doses of hexaconazole varied from 122 to 135d in the black soil and from 270
      to 845d in the red soil. Both dosages of hexaconazole did not affect NH+4-N
      content, N2-fixing bacterial populations, total bacterial diversity, and
      community structure, but transitorily decreased the populations of total bacteria
      in both soil types. In the black soil, T10 negatively affected microbial biomass
      carbon (MBC) and soil basal respiration (RB), but transitorily increased NO-3-N
      concentration and ammonia-oxidizing bacteria populations, while T1 had almost no
      effect on most of the indicators. As for red soil, both concentrations of
      fungicide significantly, but transitorily, inhibited MBC and RB, while only T10
      had a relatively long stimulatory effect on NO-3-N concentration and ammonia
      oxidizing archaea populations. This study showed that over application of
      hexaconazole is indeed harmful to soil microorganisms and may reduce soil quality
      and increase the risk of nitrogen loss in paddy soils.

PMID- 28763663
TI  - Prediction of fish catch in the Danube River based on long-term variability in
      environmental parameters and catch statistics.
AB  - The effects of physical factors on fish catch in the Serbian part of the Danube
      River were studied for period of six decades. The data on total catch for the
      Danube River from river kilometre 845 to river kilometre 1433 were collected from
      Statistical Office of the Republic of Serbia, while water level and water
      temperature data were collected from 16 water gauge stations along the
      investigated part of the Danube River for the period 1948-2009. Cross-correlation
      functions have been used to analyse the functional connection between Danube
      water level, water temperature and fish catch while ARMA model which combines
      cyclic (deterministic) and random (stochastic) components of the analysed
      sequences was used for the forecasts. The cross-correlation function showed
      negative correlation between water level and temperature as well as between water
      temperature and catch and positive correlation between water level and catch. The
      Danube water level and catch were coherent at the periods of 2.06, 4.13, 6.2,
      10.33, 20.66years, while the cross correlation function between these time series
      did not show phase lag. The results of reconstruction and forecast of water
      level, temperature, and catch of fish in the Danube River, obtained by summing
      the cyclic and stochastic components, was used for the forecast till 2029. In
      2016, seven years after, the initial forecasts were made, validity of the model
      was checked by obtaining data for water temperature, water level and fish catch
      in the Danube River for the period 2010-2015. Model gave the best prediction for
      water temperature; average standard error was 1.6 times higher for predicted
      value than for model value while for fish catch and water level they were 1.96
      and 4.97, respectively. Methods used in this work could be powerful tool for
      prediction of fish catch and serve as the basis for better fisheries management.

PMID- 28763664
TI  - Coastal stormwater wet pond sediment nitrogen dynamics.
AB  - Wet ponds are a common type of stormwater control measure (SCM) in coastal areas
      of the southeastern US, but their internal nitrogen dynamics have not been
      extensively studied. Using flow-through intact sediment core incubations, net
      sediment N2 fluxes before and after a nitrate addition from five wet ponds
      spanning a range of ages (3.25-10years old) were quantified through membrane
      inlet mass spectrometry during early summer. Multiple locations within a single
      wet pond (6.16years old) were also sampled during ambient conditions in late
      summer to determine the combined effects of depth, vegetation, and flow path
      position on net N2 fluxes at the sediment-water interface. All pond sediments had
      considerable rates of net nitrogen fixation during ambient conditions, and net N2
      fluxes during nitrate-enriched conditions were significantly correlated with pond
      age. Following a nitrate addition to simulate storm conditions, younger pond
      sediments shifted towards net denitrification, but older ponds exhibited even
      higher rates of net nitrogen fixation. The pond forebay had significantly higher
      rates of net nitrogen fixation compared to the main basin, and rates throughout
      the pond were an order of magnitude higher than the early summer experiment.
      These results identify less than optimal nitrogen processing in this common SCM,
      however, data presented here suggest that water column mixing and pond sediment
      excavation could improve the capacity of wet ponds to enhance water quality by
      permanently removing nitrogen.

PMID- 28763665
TI  - Review on characteristics of PAHs in atmosphere, anthropogenic sources and
      control technologies.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounds composed
      of multiple aromatic rings. PAHs are ubiquitous atmospheric pollutants which are
      well-recognized as carcinogenic, teratogenic and genotoxic compounds. PAHs are
      released from incomplete combustion or pyrolysis of materials containing carbon
      and hydrogen, such as coal, oil, wood and petroleum products. Understanding the
      characteristics of PAHs in atmosphere, source profiles and technologies available
      for controlling PAHs emission is essential to reduce the impacts of PAHs. This
      paper offers an overview on concentration and distribution of atmospheric PAHs,
      emission factors and distribution of PAHs in different sources, and available
      control technologies. Characteristics of atmospheric PAHs vary with
      meteorological conditions and emission sources, while characteristics of PAHs
      emission depend on burned material and combustion condition. Combination of some
      technologies may be necessary for effective removal of both low-ring and high
      ring PAHs.

PMID- 28763666
TI  - Are concentrations of alkaline earth elements in maternal hair associated with
      risk of neural tube defects?
AB  - The relationship between maternal intake of alkaline earth elements (AEEs) during
      the period of neural tube closure and the risk of neural tube defects (NTDs) is
      still unclear. We propose that AEE deficiency during the early period of
      pregnancy is associated with an elevated risk of NTDs in the offspring. In this
      study, we recruited 191 women with NTD-affected pregnancies (cases) and 261 women
      who delivered healthy infants (controls). The concentrations of four AEEs (Ca,
      Mg, Sr, Ba) in maternal hair sections that grew during early pregnancy were
      analyzed. Information on the dietary habits of the mothers was also collected by
      questionnaire. Higher concentrations of the four AEEs in hair had protective
      effects against the risk of total NTDs, with odds ratios with 95% confidence
      interval (comparing groups separated by each median level) of 0.44 (0.28-0.68)
      for Mg, 0.56 (0.36-0.87) for Ca, 0.45 (0.28-0.70) for Sr, and 0.41 (0.26-0.65)
      for Ba. Significant negative dose-response trends were identified for the
      relationships between the four AEE concentrations in maternal hair and the risks
      of anencephaly and spina bifida, but not for encephalocele. The frequencies of
      maternal consumption of fresh green vegetables, fresh fruit, and meat or fish
      were positively correlated with the concentrations of AEEs in hair. We concluded
      that the maternal intake of AEEs may play an important role in preventing NTD
      formation in offspring, and that this intake is related to maternal dietary
      habits of consuming fresh green vegetables, fresh fruit, and fish or meat.

PMID- 28763667
TI  - Characterization of a managed aquifer recharge system using multiple tracers.
AB  - Knowledge about the residence times of artificially infiltrated water into an
      aquifer and the resulting flow paths is essential to developing groundwater
      management schemes. To obtain this knowledge, a variety of tracers can be used to
      study residence times and gain information about subsurface processes. Although a
      variety of tracers exists, their interpretation can differ considerably due to
      subsurface heterogeneity, underlying assumptions, and sampling and analysis
      limitations. The current study systematically assesses information gained from
      seven different tracers during a pumping experiment at a site where drinking
      water is extracted from an aquifer close to contaminated areas and where
      groundwater is artificially recharged by infiltrating surface water. We
      demonstrate that the groundwater residence times estimated using dye and heat
      tracers are comparable when the thermal retardation for the heat tracer is
      considered. Furthermore, major ions, acesulfame, and stable isotopes (delta2H and
      delta18O) show that mixing of infiltrated water and groundwater coming from the
      regional flow path occurred and a vertical stratification of the flow system
      exist. Based on the concentration patterns of dissolved gases (He, Ar, Kr, N2,
      and O2) and chlorinated solvents (e.g., tetrachloroethene), three temporal phases
      are observed in the ratio between infiltrated water and regional groundwater
      during the pumping experiment. Variability in this ratio is significantly related
      to changes in the pumping and infiltration rates. During constant pumping rates,
      more infiltrated water was extracted, which led to a higher dilution of the
      regional groundwater. An infiltration interruption caused however, the ratio to
      change and more regional groundwater is extracted, which led to an increase in
      all concentrations. The obtained results are discussed for each tracer considered
      and its strengths and limitations are illustrated. Overall, it is demonstrated
      that aquifer heterogeneity and various subsurface processes necessitate
      application of multiple tracers to quantify uncertainty when identifying flow
      processes.

PMID- 28763668
TI  - Effects of exposure to pharmaceuticals (diclofenac and carbamazepine) spiked
      sediments in the midge, Chironomus riparius (Diptera, Chironomidae).
AB  - Human and veterinary pharmaceuticals and degradation products are continuously
      introduced into the environment. To date, there is a lack of information about
      the effects of pharmaceuticals in spiked toxicity tests with non-target
      organisms. In this study, we have evaluated the effects of exposure to two common
      pharmaceuticals in the midge Chironomus riparius in spiked sediment experiments.
      The selected pharmaceuticals are the nonsteroidal anti-inflammatory drug (NSAID):
      diclofenac (DF) and the anti-depressant drug carbamazepine (CBZ). In order to
      assess the effects of the pharmaceuticals, a chronic toxicity test with the midge
      was carried out. The endpoints survival, growth and developmental stage by means
      of biomass, were measured after 10days, and emergence rates and sex-ratio
      (male/female) were measured after 21days of exposure. Significant mortality was
      observed in organisms at day 10 with a 40% of larvae surviving in the highest
      exposure concentration of CBZ. DF decreased the emergence ratio with respect to
      the controls in organisms exposed at concentrations of 34.0MUg.g-1 whereas CBZ
      reduced the growth of the midges (30,6% with respect to the control) and induced
      a significant change in sex-ratio at concentrations of 31.4MUg.g-1. The results
      obtained in the present study indicate possible adverse effects on aquatic
      invertebrates, which should be taken into account for environmental risk
      assessment of pharmaceutical compounds in sediments.

PMID- 28763669
TI  - Effects of local land-use on riparian vegetation, water quality, and the
      functional organization of macroinvertebrate assemblages.
AB  - Land-use change is a principal factor affecting riparian vegetation and river
      biodiversity. In Chile, land-use change has drastically intensified over the last
      decade, with native forests converted to exotic forest plantations and
      agricultural land. However, the effects thereof on aquatic ecosystems are not
      well understood. Closing this knowledge gap first requires understanding how
      human perturbations affect riparian and stream biota. Identified biological
      indicators could then be applied to determine the health of fluvial ecosystems.
      Therefore, this study investigated the effects of land-use change on the health
      of riparian and aquatic ecosystems by assessing riparian vegetation, water
      quality, benthic macroinvertebrate assemblages, and functional feeding groups.
      Twenty-one sites in catchment areas with different land-uses (i.e. pristine
      forests, native forests, exotic forest plantations, and agricultural land) were
      selected and sampled during the 2010 to 2012 dry seasons. Riparian vegetation
      quality was highest in pristine forests. Per the modified Macroinvertebrate
      Family Biotic Index for Chilean species, the best conditions existed in native
      forests and the worst in agricultural catchments. Water quality and
      macroinvertebrate assemblages significantly varied across land-use areas, with
      forest plantations and agricultural land having high nutrient concentrations,
      conductivity, suspended solids, and apparent color. Macroinvertebrate assemblage
      diversity was lowest for agricultural and exotic forest plantation catchments,
      with notable non-insect representation. Collector-gatherers were the most
      abundant functional feeding group, suggesting importance independent of land-use.
      Land-use areas showed no significant differences in functional feeding groups. In
      conclusion, anthropogenic land-use changes were detectable through riparian
      quality, water quality, and macroinvertebrate assemblages, but not through
      functional feeding groups. These data, particularly the riparian vegetation and
      macroinvertebrate assemblage parameters, could be applied towards the
      conservation and management of riparian ecosystems through land-use change
      studies.

PMID- 28763670
TI  - Association between chronic exposure to different water iodine and thyroid
      cancer: A retrospective study from 1995 to 2014.
AB  - The controversy that iodine intake may increase the risk of thyroid cancer has
      heightened over the past twenty years. In this retrospective study, we mainly
      analyzed the association between water iodine and thyroid cancer and discussed
      the possible cause of the increase in thyroid cancer. This study was supported by
      three hospitals in areas with different water iodine concentration. 5574 patients
      with thyroid disease were recruited, of which 1429 patients had been diagnosed
      with thyroid cancer. These samples collectively were used to analyze the
      relationship of incidence and prevalence associated with water iodine. In
      addition, the ratio of maximum tumor diameter was analyzed. By analyzing the
      proportion of patients with thyroid cancer in thyroid diseases, we found a
      decrease in the proportion of thyroid cancer with increasing water iodine
      (P<0.0001). In addition, there was no significant correlation between the median
      water iodine and the prevalence of thyroid cancer, including papillary thyroid
      cancer (P>0.05). Meanwhile, the 5years' cumulative incidence of thyroid cancer
      increased with years (P<0.01). Comparing Cao county and Shan county, which are
      areas with high water iodine, to adequate iodine area such as in Mudan district,
      an increasing incidence is observed in 2010-2014 in Mudan district. Again, we
      observed a significant increase in the proportion of thyroid cancer with tumor
      size <1cm (P<0.01). Therefore, we concluded that cause(s) of increase in thyroid
      cancer may be ascribed to the sensitive diagnostic techniques and the improvement
      of living condition, but not water iodine.

PMID- 28763671
TI  - Temporal trends of surface urban heat islands and associated determinants in
      major Chinese cities.
AB  - There are many studies focusing on spatial variations of surface urban heat
      islands (SUHIs) in literature. In this study, MODIS land surface temperature
      (LST) data and China's Land Use/Cover Datasets (CLUDs) were used to examine the
      temporal trends of SUHIs in 31 major Chinese cities during 2001-2015 using three
      indicators: SUHI intensity (SUHII), area of the SUHI (AreaSUHI) and percentage of
      area with increasing SUHII (PAISUHII). Correlation analyses between SUHII and
      background (rural) LST (extracted from MODIS LST), vegetation coverage (reflected
      by MODIS EVI data) and anthropogenic heat release (reflected by nighttime light
      data) were performed from temporal rather than spatial perspectives. Our findings
      showed that the SUHII and AreaSUHI in urbanized areas increased significantly in
      most cities in summer days, whereas they increased significantly in approximately
      half and more than half of the cities in summer and winter nights, respectively.
      In summer days, summer nights and winter nights, the PAISUHII was approximately
      80% and over 50% in union areas and the 20km buffer, respectively. Correlation
      analyses indicated that the SUHII in stable urban areas was negatively correlated
      with the background LST in summer and winter days for most cities, especially in
      northern China. A reduction in vegetation contributed to the increasing SUHII in
      urbanized areas in summer days and nights. The increasing anthropogenic heat
      release was an important factor for increases in the SUHII in urbanized areas.

PMID- 28763672
TI  - Application of thermography for monitoring stomatal conductance of Coffea arabica
      under different shading systems.
AB  - Stomatal regulation is a key process in the physiology of Coffea arabica (C.
      arabica). Intrinsically linked to photosynthesis and water relations, it provides
      insights into the plant's adaptive capacity, survival and growth. The ability to
      rapidly quantify this parameter for C. arabica under different agroecological
      systems would be an indispensable tool. Using a Flir E6 MIR Camera, an index that
      is equivalent to stomatal conductance (Ig) was compared with stomatal conductance
      measurements (gs) in a mature coffee plantation. In order to account for varying
      meteorological conditions between days, the methods were also compared under
      stable meteorological conditions in a laboratory and Ig was also converted to
      absolute stomatal conductance values (g1). In contrast to typical plant
      thermography methods which measure indices once per day over an extended time
      period, we used high resolution hourly measurements over daily time series with 9
      sun and 9 shade replicates. Eight daily time series showed a strong correlation
      between methods, while the remaining 10 were not significant. Including several
      other meteorological parameters in the calculation of g1 did not contribute to
      any stronger correlation between methods. Total pooled data (combined daily
      series) resulted in a correlation of rho=0.66 (P<=2.2e-16), indicating that our
      approach is particularly useful for situations where absolute values of stomatal
      conductance are not required, such as for comparative purposes, screening or
      trend analysis. We use the findings to advance the protocol for a more accurate
      methodology which may assist in quantifying advantageous microenvironment designs
      for coffee, considering the current and future climates of coffee growing
      regions.

PMID- 28763673
TI  - Performance assessment of individual and ensemble data-mining techniques for
      gully erosion modeling.
AB  - Gully erosion is identified as an important sediment source in a range of
      environments and plays a conclusive role in redistribution of eroded soils on a
      slope. Hence, addressing spatial occurrence pattern of this phenomenon is very
      important. Different ensemble models and their single counterparts, mostly data
      mining methods, have been used for gully erosion susceptibility mapping; however,
      their calibration and validation procedures need to be thoroughly addressed. The
      current study presents a series of individual and ensemble data mining methods
      including artificial neural network (ANN), support vector machine (SVM), maximum
      entropy (ME), ANN-SVM, ANN-ME, and SVM-ME to map gully erosion susceptibility in
      Aghemam watershed, Iran. To this aim, a gully inventory map along with sixteen
      gully conditioning factors was used. A 70:30% randomly partitioned sets were used
      to assess goodness-of-fit and prediction power of the models. The robustness, as
      the stability of models' performance in response to changes in the dataset, was
      assessed through three training/test replicates. As a result, conducted
      preliminary statistical tests showed that ANN has the highest concordance and
      spatial differentiation with a chi-square value of 36,656 at 95% confidence
      level, while the ME appeared to have the lowest concordance (1772). The ME model
      showed an impractical result where 45% of the study area was introduced as highly
      susceptible to gullying, in contrast, ANN-SVM indicated a practical result with
      focusing only on 34% of the study area. Through all three replicates, the ANN-SVM
      ensemble showed the highest goodness-of-fit and predictive power with a
      respective values of 0.897 (area under the success rate curve) and 0.879 (area
      under the prediction rate curve), on average, and correspondingly the highest
      robustness. This attests the important role of ensemble modeling in congruently
      building accurate and generalized models which emphasizes the necessity to
      examine different models integrations. The result of this study can prepare an
      outline for further biophysical designs on gullies scattered in the study area.

PMID- 28763674
TI  - High-spatiotemporal-resolution ship emission inventory of China based on AIS data
      in 2014.
AB  - Ship exhaust emissions have been considered a significant source of air
      pollution, with adverse impacts on the global climate and human health. China, as
      one of the largest shipping countries, has long been in great need of in-depth
      analysis of ship emissions. This study for the first time developed a
      comprehensive national-scale ship emission inventory with 0.005 degrees *0.005
      degrees  resolution in China for 2014, using the bottom-up method based on
      Automatic Identification System (AIS) data of the full year of 2014. The emission
      estimation involved 166,546 unique vessels observed from over 15billion AIS
      reports, covering OGVs (ocean-going vessels), CVs (coastal vessels) and RVs
      (river vessels). Results show that the total estimated ship emissions for China
      in 2014 were 1.1937*106t (SO2), 2.2084*106t (NOX), 1.807*105t (PM10), 1.665*105t
      (PM2.5), 1.116*105t (HC), 2.419*105t (CO), and 7.843*107t (CO2, excluding RVs),
      respectively. OGVs were the main emission contributors, with proportions of 47%
      74% of the emission totals for different species. Vessel type with the most
      emissions was container (~43.6%), followed by bulk carrier (~17.5%), oil tanker
      (~5.7%) and fishing ship (~4.9%). Monthly variations showed that emissions from
      transport vessels had a low point in February, while fishing ship presented two
      emission peaks in May and September. In terms of port clusters, ship emissions in
      BSA (Bohai Sea Area), YRD (Yangtze River Delta) and PRD (Pearl River Delta)
      accounted for ~13%, ~28% and ~17%, respectively, of the total emissions in China.
      On the contrast, the average emission intensities in PRD were the highest,
      followed by the YRD and BSA regions. The establishment of this high
      spatiotemporal-resolution ship emission inventory fills the gap of national-scale
      ship emission inventory of China, and the corresponding ship emission
      characteristics are expected to provide certain reference significance for the
      management and control of the ship emissions.

PMID- 28763675
TI  - Transcriptional and epigenetic control in mouse pluripotency: lessons from in
      vivo and in vitro studies.
AB  - Pluripotent cells were first derived from mouse blastocysts several decades ago.
      Since then, our knowledge of the molecular events that occur in the pre
      implantation embryo has been vastly progressing. The emergence of epigenetics has
      revolutionized stem cell and developmental biology and further deepened our
      understanding of the underlying molecular mechanisms controlling the early embryo
      development. In particular, the emergence of massive parallel sequencing
      technologies has opened new avenues and became indispensable tools in modern
      biology. Additionally, development of new and exciting techniques for genome
      manipulation (TALEN and CRISPR/Cas9) and in vivo imaging provide unique
      opportunities to perturb and trace biological systems at very high resolution.
      Finally, recent single-cell - omics combined with sophisticated computational
      methodologies allow accurate, quantitative measurements for deconvolution of
      cellular variation in complex cell populations. Collectively, these achievements
      enabled the detailed characterization and monitoring of various cell states and
      trajectories during early stages of embryonic development. Here we review recent
      studies of the transcriptional and epigenetic changes during very early stages of
      mouse embryo development and compare these with pluripotent cells grown in vitro
      under different culture conditions. We discuss whether the in vitro cell states
      have an 'epi-phenocopy' in the embryo and refine our understanding of the
      circuitries controlling pluripotency and lineage commitment during early stages
      of mouse development.

PMID- 28763676
TI  - Impact of intervention on metabolic outcomes among dropouts with type 2 diabetes.
AB  - PURPOSE: The aim of this study was to evaluate the effect of an individual
      intervention given by health care professionals to dropouts with type 2 diabetes
      (T2D) on their metabolic profile. MATERIALS/METHODS: In 2010, we identified 356
      T2D dropouts in Vantaa Health Centre, Finland. At the baseline visit the
      participants' status was assessed including laboratory tests. Diabetes counseling
      was given, and drug treatment was enhanced when needed. The follow-up visit was
      performed 13 to 30 months later including the same assessments as performed at
      the baseline visit. The dropouts who attended the follow-up visit formed the
      study group. One third (n=115) of the dropouts participated in the follow-up
      visit. RESULTS: The study participants (mean age 61.4 years) were older than the
      non-participants (mean age 58.5 years) (p=0.009). After the intervention the
      proportion of participants with hemoglobin A1c>=9% (75mmol/mol) decreased from
      15.5% to 5.2% (p=0.004). Improvements were also observed in general in hemoglobin
      A1c, from 6.6% (49mmol/mol) to 6.3% (45mmol/mol) (p=0.001), in total cholesterol,
      from 4.9mmol/l to 4.5mmol/l (p=0.011), in low-density lipoprotein cholesterol,
      from 2.9mmol/l to 2.6mmol/l (p=0.015) and in diastolic blood pressure, from
      90mmHg to 84mmHg (p=0.001). CONCLUSIONS: Dropouts with T2D were difficult to
      bring back to the public health care system, especially men under the age of 60
      years. Dropouts who participated in the intervention showed improvements in
      several metabolic outcomes.

PMID- 28763677
TI  - Genetic basis of enzymatic resistance of E. coli to aminoglycosides.
AB  - PURPOSE: Over the past years, an increase in resistance to aminoglycosides has
      been observed among Enterobacteriaceae rods. This resistance development reduces
      therapeutic options for infections caused by multidrug-resistance organisms.
      Because of the changing epidemiology of extended-spectrum beta-lactamases (ESBLs)
      and resistance to aminoglycosides, we investigated the prevalence of the aac(3)
      Ia, aac(6')-Ib, ant(4')-IIa, ant(2")-Ia, and aph(3")-Ib genes encoding
      aminoglycoside-modifying enzymes (AMEs) in ESBL-producing Escherichia coli as
      well as ESBL-non-producing isolates. To understand bacterial resistance to
      aminoglycoside antibiotics, we estimated resistance phenotypes and the presence
      of genes responsible for this resistance. MATERIALS AND METHODS: The study was
      conducted on 44 E.coli strains originated from patients hospitalized at
      University Hospital of Bialystok. MIC values were obtained for gentamicin,
      amikacin, netilmicin, and tobramycin. Isolates were tested for the presence of
      the aac(3)-Ia, aac(6')-Ib, ant(4')-IIa, ant(2")-Ia, and aph(3")-Ib genes with the
      use of the PCR technique. RESULTS: Resistance to aminoglycosides was found in
      79.5% of the isolates. The highest percentages of resistance were observed for
      tobramycin (70,5%) and gentamicin (59%), followed by netilmicin (43.2%) and
      amikacin (11.4%). PCR assays revealed the presence of aac(6')-Ib among 26 (59.2%)
      strains, aph(3")-Ib among 16 (36.2%), aac(3)-Ia among 7 (15.9%), and ant(2")-Ia
      among 2 (4.6%) strains. CONCLUSIONS: The enzymatic resistance against
      aminoglycosides in northeastern Poland among clinical isolates of E. coli is
      predominantly caused by aac(6')-Ib and aph(3")-Ib. Amikacin may be used for
      therapy of infections caused by ESBL-producing E. coli, because of the low rates
      of resistance.

PMID- 28763678
TI  - Detecting temporal changes in acoustic scenes: The variable benefit of selective
      attention.
AB  - Four experiments investigated change detection in acoustic scenes consisting of a
      sum of five amplitude-modulated pure tones. As the tones were about 0.7 octave
      apart and were amplitude-modulated with different frequencies (in the range 2-32
      Hz), they were perceived as separate streams. Listeners had to detect a change in
      the frequency (experiments 1 and 2) or the shape (experiments 3 and 4) of the
      modulation of one of the five tones, in the presence of an informative cue
      orienting selective attention either before the scene (pre-cue) or after it (post
      cue). The changes left intensity unchanged and were not detectable in the
      spectral (tonotopic) domain. Performance was much better with pre-cues than with
      post-cues. Thus, change deafness was manifest in the absence of an appropriate
      focusing of attention when the change occurred, even though the streams and the
      changes to be detected were acoustically very simple (in contrast to the
      conditions used in previous demonstrations of change deafness). In one case, the
      results were consistent with a model based on the assumption that change
      detection was possible if and only if attention was endogenously focused on a
      single tone. However, it was also found that changes resulting in a steepening of
      amplitude rises were to some extent able to draw attention exogenously. Change
      detection was not markedly facilitated when the change produced a discontinuity
      in the modulation domain, contrary to what could be expected from the perspective
      of predictive coding.

PMID- 28763679
TI  - Multivariate pattern analysis of event-related potentials predicts the subjective
      relevance of everyday objects.
AB  - Potentially decision-relevant stimuli have been proposed to undergo immediate
      semantic processing. The current study investigated whether information regarding
      the general desirability ('Wanting') of visually presented 'everyday' objects was
      rapidly and automatically processed. Participants completed a foreground task
      while their electroencephalogram (EEG) was recorded, and task-irrelevant images
      were presented in the background. Following this, participants rated the images
      with regards to Wanting and the potentially related attributes of Relevance,
      Familiarity, Aesthetic Pleasantness and Time Reference. Multivariate pattern
      classification was used to predict the ratings from patterns of EEG data.
      Prediction of Wanting and Relevance was possible between 100 and 150ms following
      stimulus presentation. The other dimensions could not be predicted. Wanting and
      Relevance ratings were highly correlated and displayed similar feature weight
      maps. The current results suggest that the general desirability and subjective
      relevance of everyday objects is rapidly and automatically processed for a wide
      range of visual stimuli.

PMID- 28763680
TI  - Dysfunctional metacognition across psychopathologies: A meta-analytic review.
AB  - BACKGROUND: Dysfunctions in metacognition have been reported in individuals with
      anxiety disorders. Although recent studies have examined metacognition in other
      disorders, how dysfunctional metacognition compares across disorders is not
      clear. This review aimed to ascertain the importance of dysfunctional
      metacognition in various psychopathologies, and to identify similarities and
      differences in metacognitive profiles across disorders. METHODS: Forty-seven
      studies were selected from 586 articles published between 1990 and August 2015,
      including a total sample of 3772 patients and 3376 healthy individuals. Studies
      that measured metacognition using the Meta-Cognitions Questionnaire (MCQ) and its
      variants were included. We conducted five meta-analyses including 49 to 55 effect
      sizes, comparing psychiatric patients to healthy individuals on respective
      metacognitive dimensions of the MCQ. RESULTS: We found elevated metacognitive
      dysfunctions in patients, as a group, on all MCQ dimensions. Group effects were
      large and robust for the two negative beliefs (i.e., beliefs about the
      uncontrollability and danger of thoughts, and beliefs about the need to control
      thoughts), and moderate and unstable for the positive beliefs. Patients showed
      decreased cognitive confidence and heightened cognitive self-consciousness on
      moderate to large levels. Moderator analyses revealed that negative beliefs about
      uncontrollability and danger of thoughts were most prevalent in generalized
      anxiety disorder, whereas heightened cognitive self-consciousness was more
      characteristic in obsessive-compulsive disorder. Generalized anxiety disorder,
      obsessive-compulsive disorder and eating disorders manifested more similar
      metacognitive profiles than other disorders. CONCLUSIONS: Our findings supported
      dysfunctional metacognition as common processes across psychopathologies, with
      certain dimensions being more prevalent in particular disorders.

PMID- 28763681
TI  - Association between home-visit nursing utilization and all-cause hospitalization
      among long-term care insurance beneficiaries: A retrospective cohort study.
AB  - BACKGROUND: Ensuring and improving long-term care services that use limited
      healthcare resources more efficiently is a major concern for many aging
      societies. OBJECTIVES: The aim of this study was to investigate the relationship
      between use of home-visit nursing services and all-cause hospitalization in a
      home-visit nursing-recommended group. DESIGN: A retrospective cohort study.
      SETTING: Population-based sample of long-term care insurance beneficiaries from
      the long-term care insurance 2002-2013 claims database in South Korea.
      PARTICIPANTS: Long-term care insurance beneficiaries who need one or more types
      of nursing care were defined as the home-visit nursing -recommended group
      (n=4173). MEASUREMENTS: The dependent variable in this study was all-cause
      hospitalization in the home-visit nursing-recommended population. Multivariate
      Cox proportional hazards regression analysis was used to identify the association
      between home-visit nursing service use and all-cause hospitalization. RESULTS: A
      total of 3.8% of the subjects used home-visit nursing services. When participants
      who used home-visit nursing services were set as the reference group,
      participants who did not use home-visit nursing services had a higher risk of
      hospitalization (hazard ratio [HR]=1.25, 95% confidence interval [CI]=1.07-1.47).
      Additionally, participants who did not use home-visit nursing services and who
      did not have a caregiver showed a marked increase in the risk of hospitalization
      (HR=6.81, 95% CI=1.17-39.66). Participants who did not use home-visit nursing
      services with greater comorbidity showed a considerable increase in risk of
      hospitalization (HR=1.36, 95% CI=1.09-1.70). CONCLUSIONS: Non-use of home-visit
      nursing services was associated with an increased risk of all-cause
      hospitalization in the home-visit nursing-recommended population. The present
      results suggest that the use of home-visit nursing services reduced the risk of
      hospitalization. Moreover, home-visit nursing may play an essential role in
      reducing hospitalization risk in the absence of caregiver support.

PMID- 28763682
TI  - Normal contractile algorithm of swallowing related muscles revealed by needle EMG
      and its comparison to videofluoroscopic swallowing study and high resolution
      manometry studies: A preliminary study.
AB  - The purpose of this study was to investigate the function and importance of
      infrahyoid muscles with the suprahyoid muscles during swallowing, and to
      investigate swallowing sequences using kinematic analysis, high-resolution
      manometry (HRM) and electromyography (EMG). As a preliminary study, ten healthy
      subjects were prospectively enrolled. A needle EMG evaluated the onset latency,
      peak latency and duration of the suprahyoid and infrahyoid muscles. HRM measured
      the time intervals among the velopharynx, tongue base, and upper esophageal
      sphincter. We also evaluated hyoid motion using an automated kinematic analysis
      software(r) (AKAS). All of these parameters were synchronized with a tilting
      motion of the epiglottis. In the EMG analysis, the activations of the suprahyoid
      muscles developed about 300ms earlier than that of the infrahyoid muscles. There
      was a significant relationship between the differences of suprahyoid and
      infrahyoid muscles' latency and total duration of the hyoid motion (p<0.05). The
      interval time of anterior hyoid motion has a significant correlation in the upper
      esophageal sphincter (UES) opening time. In conclusions, the functions of the
      infrahyoid muscles are also as important as that of the suprahyoid muscles for
      prolonged laryngeal elevation and UES opening. Moreover, kinematic analysis of
      videofluoroscopic swallowing study (VFSS) and HRM studies could reflect results
      of needle EMG study and replace EMG study.

PMID- 28763683
TI  - Semiquantitative screening of trace combustion-derived volatile substances in the
      blood of fire victims using NeedlEx(r) headspace gas chromatography/mass
      spectrometry.
AB  - BACKGROUND: Various autopsy findings are used for the diagnosis of burning death,
      including inhalation injury, soot in the respiratory tract, vital reaction, blood
      carboxyhemoglobin (COHb), and blood cyanide. However, not all findings are
      necessarily complete, and autopsy diagnosis can be difficult in cases where there
      are few findings. In this study, we analyzed combustion-derived volatile
      substances (CVSs) in post-mortem blood in fire-related cases, focusing on those
      that occur when buildings and furniture thermally decompose during a fire, and
      evaluated these as potential new autopsy findings. METHODS: The blood CVSs of 61
      fire-related cases from 2013 to 2015 were analyzed by a rapid and operationally
      simple method that employed a gas chromatograph-mass spectrometer coupled to a
      NeedlEx(r), an extraction needle packed with a medium that selectively adsorbs
      volatile organic compounds. RESULTS: A total of 39 types of aliphatic and
      aromatic hydrocarbons were detected in the blood of fire victims. They could be
      detected even in post-mortem blood with COHb <10%, cyanide concentration
      <0.25MUg/ml, and no soot in the respiratory tract. Styrene was detected in all
      cases except for one case of burning suicide with kerosene. The blood CVSs could
      be readily differentiated between the victims of building fires, self-immolation
      with kerosene, and self-immolation with gasoline: the presence of alpha
      methylstyrene with a large amount styrene indicated a building fire; the
      detection of C9-C12 aliphatic hydrocarbons and C3 alkylbenzenes suggested a
      kerosene-related fire; and the detection of large amount of toluene and C3
      alkylbenzenes indicated a gasoline-related fire. The number of blood CVSs
      detected for the building fire victims showed correlations with COHb level,
      cyanide concentration, and the amount of soot. With self-immolation, the number
      of blood CVSs detected showed weak correlation with COHb level, cyanide
      concentration, or amount of soot. CONCLUSION: Analysis of blood CVSs enabled the
      identification of the type of fire-related death, which is impossible by
      conventional autopsy findings.

PMID- 28763684
TI  - Bloodstains on woven fabric: Simulations and experiments for quantifying the
      uncertainty on the impact and directional angles.
AB  - Bloodstain pattern analysis considers stains on various porous and non-porous
      surfaces, for the purpose of crime scene reconstruction. On non-porous surfaces,
      several studies relate the impact conditions of drops to the inspection of stain
      shapes. Stains on porous surfaces like fabrics have been relatively less
      explored. The phenomenon of imbibition of blood into the fabric after impact adds
      further complexity in retrieving information on the impacting conditions. The
      present work studies experimentally and numerically the formation of drip stains
      on a woven fabric. The proposed methodology first relies on Darcy's law to
      measure the imbibition characteristics of the fabric through a set of simple
      imbibition experiments. Next, the fabric properties are fed into a numerical
      model to predict the growth of the bloodstain after impact of a droplet.
      Experiments at different drop release heights and impact angles are compared with
      the numerical simulations. The uncertainties induced by the fabric on the
      determination of the impact and directional angles are explained and quantified.

PMID- 28763685
TI  - Viscoelasticity of articular cartilage: Analysing the effect of induced stress
      and the restraint of bone in a dynamic environment.
AB  - The aim of this study was to determine the effect of the induced stress and
      restraint provided by the underlying bone on the frequency-dependent storage and
      loss stiffness (for bone restraint) or modulus (for induced stress) of articular
      cartilage, which characterise its viscoelasticity. Dynamic mechanical analysis
      has been used to determine the frequency-dependent viscoelastic properties of
      bovine femoral and humeral head articular cartilage. A sinusoidal load was
      applied to the specimens and out-of-phase displacement response was measured to
      determine the phase angle, the storage and loss stiffness or modulus. As induced
      stress increased, the storage modulus significantly increased (p < 0.05). The
      phase angle decreased significantly (p < 0.05) as the induced stress increased;
      reducing from 13.1 degrees  to 3.5 degrees . The median storage stiffness ranged
      from 548N/mm to 707N/mm for cartilage tested on-bone and 544N/mm to 732N/mm for
      cartilage tested off-bone. On-bone articular cartilage loss stiffness was
      frequency independent (p > 0.05); however, off-bone, articular cartilage loss
      stiffness demonstrated a logarithmic frequency-dependency (p < 0.05). In
      conclusion, the frequency-dependent trends of storage and loss moduli of
      articular cartilage are dependent on the induced stress, while the restraint
      provided by the underlying bone removes the frequency-dependency of the loss
      stiffness.

PMID- 28763686
TI  - In silico molecular docking studies of new potential 4-phthalazinyl-hydrazones on
      selected Trypanosoma cruzi and Leishmania enzyme targets.
AB  - Recently, a series of 4-phthalazinyl-hydrazones under its E-configuration have
      exhibited excellent in vitro antichagasic and antileishmanial profiles.
      Preliminary assays on both parasites suggested that the most active derivatives
      act through oxidative and nitrosative stress mechanisms; however, their exact
      mode of actions as anti-trypanosomal and anti-leishmanial agents have not been
      completely elucidated. This motivated to perform a molecular docking study on
      essential trypanosomatid enzymes such as superoxide dismutase (SOD),
      trypanothione reductase (TryR), cysteine-protease (CP) and pteridine reductase 1
      (PTR1). In addition, to understand the experimental results of nitric oxide
      production obtained for infected macrophages with Leishmania parasite, a
      molecular docking was evaluated on nitric oxide synthase (iNOS) enzyme of Rattus
      norvegicus. Both diastereomers (E and Z) of the 4-phthalazinyl-hydrazones were
      docked on the mentioned targets. In general, molecular docking on T. cruzi
      enzymes revealed that the E-diastereomers exhibited lower binding energies than Z
      diastereomers on the Fe-SOD and CP enzymes, while Z-diastereomers showed lower
      docking energies than E-isomers on TryR enzyme. For the Leishmania docking
      studies, the Z-isomers exhibited the best binding affinities on the PTR1 and iNOS
      enzymes, while the TryR enzyme showed a minor dependence with the
      stereoselectivity of the tested phthalazines. However, either the structural
      information of the ligand-enzyme complexes or the experimental data suggest that
      the significant antitrypanosomatid activity of the most active derivatives is not
      associated to the inhibition of the SOD, CP and PTR1 enzymes, while the TryR
      inhibition and nitric oxide generation in host cells emerge as interesting
      antitrypanosomatid therapeutic targets.

PMID- 28763687
TI  - Similarity/dissimilarity calculation methods of DNA sequences: A survey.
AB  - DNA sequence similarity/dissimilarity analysis is a fundamental task in
      computational biology, which is used to analyze the similarity of different DNA
      sequences for learning their evolutionary relationships. In past decades, a large
      number of similarity analysis methods for DNA sequence have been proposed due to
      the ever-growing demands. In order to learn the advances of DNA sequence
      similarity analysis, we make a survey and try to promote the development of this
      field. In this paper, we first introduce the related knowledge of DNA
      similarities analysis, including the data sets, similarities distance and output
      data. Then, we review recent algorithmic developments for DNA similarity analysis
      to represent a survey of the art in this field. At last, we summarize the
      corresponding tendencies and challenges in this research field. This survey
      concludes that although various DNA similarity analysis methods have been
      proposed, there still exist several further improvements or potential research
      directions in this field.

PMID- 28763688
TI  - Prediction of lysine propionylation sites using biased SVM and incorporating four
      different sequence features into Chou's PseAAC.
AB  - Lysine propionylation is an important and common protein acylation modification
      in both prokaryotes and eukaryotes. To better understand the molecular mechanism
      of propionylation, it is important to identify propionylated substrates and their
      corresponding propionylation sites accurately. In this study, a novel
      bioinformatics tool named PropPred is developed to predict propionylation sites
      by using multiple feature extraction and biased support vector machine. On the
      one hand, various features are incorporated, including amino acid composition,
      amino acid factors, binary encoding, and the composition of k-spaced amino acid
      pairs. And the F-score feature method and the incremental feature selection
      algorithm are adopted to remove the redundant features. On the other hand, the
      biased support vector machine algorithm is used to handle the imbalanced problem
      in propionylation sites training dataset. As illustrated by 10-fold cross
      validation, the performance of PropPred achieves a satisfactory performance with
      a Sensitivity of 70.03%, a Specificity of 75.61%, an accuracy of 75.02% and a
      Matthew's correlation coefficient of 0.3085. Feature analysis shows that some
      amino acid factors play the most important roles in the prediction of
      propionylation sites. These analysis and prediction results might provide some
      clues for understanding the molecular mechanisms of propionylation. A user
      friendly web-server for PropPred is established at 123.206.31.171/PropPred/.

PMID- 28763689
TI  - Investigation of novel pharmacological chaperones for Gaucher Disease.
AB  - Beta-Glucocerebrosidase (GBA) is a lysosomal protein that is responsible for the
      hydrolysis of glycosylceramide into glucose and ceramide. Mutations in GBA lead
      to the accumulation of glycosylceramide in the lysosome causing an enlargement of
      the spleen and the liver and skeletal deformations. This disease is called
      Gaucher Disease. Enzyme replacement therapies and substrate reduction methods
      that are used to treat Gaucher Disease fail when the disease is neuropathic
      because they fail to pass the blood brain barrier. In this work, QSAR, virtual
      screening, docking and molecular dynamics simulations were performed to obtain a
      set of compounds that might be pharmacological chaperones for GBA. ZINC Database
      was screened using ligand-based and structure-based pharmacophore hypotheses.
      After docking of these molecules and filtration based on druglikeness, top
      ranking ligands were identified and their binding stabilities were examined using
      MD simulations. As a result, seven new compounds that can potentially cross the
      blood brain barrier were proposed as GBA inhibitors. Three of the seven compounds
      have a tricyclic pyrido-thieno-pyrimidine scaffold and one has the dioxino
      quinolone scaffold. Derivatives of these scaffolds have been reported as
      antiallergic agents, antibiotic and anticancer compounds. These results offer a
      new approach for the development of new drugs against neuropathic Gaucher Disease
      Type 2 and Type 3.

PMID- 28763690
TI  - Protein secondary structure prediction: A survey of the state of the art.
AB  - Protein secondary structure prediction (PSSP) is a fundamental task in protein
      science and computational biology, and it can be used to understand protein 3
      dimensional (3-D) structures, further, to learn their biological functions. In
      the past decade, a large number of methods have been proposed for PSSP. In order
      to learn the latest progress of PSSP, this paper provides a survey on the
      development of this field. It first introduces the background and related
      knowledge of PSSP, including basic concepts, data sets, input data features and
      prediction accuracy assessment. Then, it reviews the recent algorithmic
      developments of PSSP, which mainly focus on the latest decade. Finally, it
      summarizes the corresponding tendencies and challenges in this field. This survey
      concludes that although various PSSP methods have been proposed, there still
      exist several further improvements or potential research directions. We hope that
      the presented guidelines will help nonspecialists and specialists to learn the
      critical progress in PSSP in recent years.

PMID- 28763691
TI  - Treatment of elderly patients or patients who are performance status 2 (PS2) with
      advanced Non-Small Cell Lung Cancer without epidermal growth factor receptor
      (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations - Still a
      daily challenge.
AB  - Cytotoxic chemotherapy remains the core treatment strategy for patients with
      advanced non-small cell lung cancer (NSCLC) with tumours that do not have
      actionable molecular alterations, such as epidermal growth factor receptor (EGFR)
      sensitising mutations, anaplastic lymphoma kinase (ALK) translocations or ROS1
      translocations. Age and performance status (PS) are two pivotal factors to guide
      treatment decisions regarding the use of chemotherapy in lung cancer patients.
      Lung cancer is predominantly a disease of the elderly, with more than two-thirds
      of patients aged >=65 years, the current definition of 'elderly'. The prevalence
      of poor PS, as estimated by patients themselves, can be as high as 50%. Both the
      elderly and PS2 patients are underrepresented in clinical trials. Therefore,
      optimising treatment strategy for the subgroup of elderly or PS2 patients with
      advanced NSCLC remains challenging as a result of a paucity of clinical trial
      data. The current review focusses on the elderly or PS2 patients without
      actionable oncogenic drivers and attempts to summarise current available data on
      recent treatments trials including angiogenesis inhibitors and immune-checkpoint
      inhibitors.

PMID- 28763692
TI  - Association of the oestrogen receptor beta with hormone status and prognosis in a
      cohort of female patients with colorectal cancer.
AB  - BACKGROUND: The oestrogen receptor beta (ERbeta) is the predominant oestrogen
      receptor in the normal colon mucosa and has been reported to exert anti
      proliferative and pro-apoptotic effects. However, the role of ERbeta in
      colorectal cancer (CRC) progression remains unclear. AIM: To investigate the role
      of ERbeta and its association with hormone status and lifestyle indicators in a
      female cohort of patients with CRC. METHODS: Tissue microarrays of primary CRC
      tumour samples from 320 female patients were conducted with a monoclonal anti
      ERbeta antibody. The staining intensity was evaluated using immunohistochemistry.
      The association of ERbeta expression with overall survival, disease-free
      survival, hormone status and lifestyle was evaluated, and effect estimators with
      95% confidence intervals (CIs) were reported. RESULTS: Among the 314 samples with
      successfully detected ERbeta, 182 (58%) had low expression and 132 (42%) had high
      expression. The Cox multivariate analysis indicated that patients with high
      ERbeta expression had a decreased risk of overall mortality by 50% (hazard ratio
      [HR], 0.50; CI, 0.30-0.83) and of cancer recurrence by 76% (HR, 0.24; CI, 0.11
      0.52) after adjusting for age, tumour-node-metastasis stage and tumour
      intravascular invasion. Furthermore, high ERbeta expression was significantly
      correlated with shorter breastfeeding time and longer use of hormone replacement
      therapy. No association was found between ERbeta expression and lifestyle
      indicators. CONCLUSION: Elevated ERbeta expression is independently associated
      with a better prognosis and hormone status but not lifestyle indicators in female
      CRC patients.

PMID- 28763693
TI  - Validation of simplified FABS scale to predict stroke mimics in a Chinese
      population undergoing intravenous thrombolysis.
AB  - OBJECTIVES: A large number of suspected stroke patients undergoing intravenous
      thrombolysis are stroke mimics (SMs). In this study, we sought to revise the FABS
      scale for screening and stratifying SMs from acute ischemic stroke (AIS) in a
      Chinese stroke population receiving fibrinolytic therapy. PATIENTS AND METHODS:
      The simplified FABS (sFABS) scale includes 4 items with 1 point for each item
      present: absence of facial droop, negative history of atrial fibrillation, age
      <50years, systolic blood pressure <150mm Hg at presentation. We evaluated
      consecutive suspected stroke patients undergoing intravenous thrombolysis in our
      stroke center for validation of sFABS scale. Diagnosis of SMs was based on
      absence of acute ischemic lesions on first and second diffusion weight imaging
      sequence in addition to an alternate diagnosis at discharge. RESULTS: A total of
      190 AIS patients and 28 SMs were included in this study from December 2015 to
      February 2017. The sFABS scale showed excellent discrimination (C statistic:
      0.928, 95% CI: 0.887-0.969, P<0.001). The Hosmer and Lemeshow goodness of fit
      test showed that the sFABS scale also had a good calibration (Cox and Snell
      R2=0.294, Nagelkerke R2=0.549). The plot of observed versus predicted risk of SMs
      showed high correlation (Pearson correlation coefficient: 0.983) between observed
      and predicted risk in our registered stroke population. CONCLUSION: The sFABS
      scale had excellent discrimination and good calibration abilities to predict SMs
      among a Chinese stroke population receiving tPA therapy. Further imaging
      evaluation may be necessary before the use of tPA if the sFABS score is higher.

PMID- 28763694
TI  - Changing messages about place of birth in Mother and Baby magazine between 1956
      and 1992.
AB  - OBJECTIVE: this paper explores changing messages about place of birth offered to
      women by Mother and Baby magazine, a UK publication aimed at a general readership
      DESIGN: the research uses an historical perspective to explore changing messages
      about place of birth in Mother and Baby magazine between 1956-1992. It analyses
      the content and medium of the magazine through a narrative and semiotic approach.
      SETTING: the UK between the mid-1950s and 1990s. The period was a time of
      significant change in the maternity services, at both a philosophical and
      organisational level with a move towards hospital rather than home birth and a
      dominant discourse which privileged medical models of care over social ones.
      PARTICIPANTS: producers and consumers of Mother and Baby magazine FINDINGS:
      Mother and Baby moved from an assumption of home birth to a focus on hospital
      birth, reflecting national changes in policy. The magazine moved from a social to
      a risk focused medical view of birth, with an emphasis on the safety of the baby
      and the sacrifice of the mother. These changes can be traced through both the
      organisation and the language of content between 1956 and 1992. However, home
      birth was always offered to readers as a viable, if increasingly niche, option.
      This reflected the magazine's need to appeal to its readers as consumers; both in
      consumption of the magazine and of maternity care. CONCLUSIONS: the evidence
      suggests that Mother and Baby magazine mirrored elements of the prevailing policy
      discourse around place of birth. However, it always gave space to other
      narratives. In doing so it reminds us of the complexity about how messages about
      labour and birth are told and received. It gives insight into ways in which the
      media lead and reflect change and the impact this might have on decision making
      by women.

PMID- 28763695
TI  - Anterior mediastinal solitary fibrous tumor resection by da Vinci(r) Surgical
      System in obese patient.
AB  - INTRODUCTION: Solitary fibrous tumors are uncommon soft tissue tumors initially
      reported only in the pleura but, in recent years, they have been described at
      many extra pleural sites, such as mediastinum. The treatment of choice is the
      extensive surgical resection that is curative for most benign lesions.
      PRESENTATION OF THE CASE: We present the case of solitary fibrous tumor of the
      anterior mediastinum in obese patient (BMI: 34.3) undergoing complete surgical
      resection by robotic-assisted thoracoscopic surgery with da Vinci(r) Surgical
      System. DISCUSSION/CONCLUSION: Robotic-assisted thoracoscopic surgery with da
      Vinci(r) Surgical System is an interesting option for obese patient, at higher
      risk for deep sternal wound infection.

PMID- 28763696
TI  - Long-term observation and treatment of a widespread intraductal papillary
      neoplasm of the bile duct extending from the intrapancreatic bile duct to the
      bilateral intrahepatic bile duct: A case report.
AB  - INTRODUCTION: Few studies have reported the long-term outcomes of surgical
      resected intraductal papillary neoplasm of the bile duct (IPNB). Here, we
      describe the long-term observation and treatment of a case of widespread IPNB.
      PRESENTATION OF CASE: A 57-year-old male was referred to our hospital due to
      jaundice and dilation of the intrahepatic bile duct. Computed tomography showed
      dilation and irregularities of the right intrahepatic and extrahepatic bile ducts
      together with a 3cm nodule in the common hepatic duct. Peroral cholangioscopy
      revealed mucinous discharge from the ampulla of Vater, which resulted in a
      diagnosis of IPNB. A biopsy of the nodule and the bile duct revealed papillary
      adenoma in all of them. Right hepatectomy, caudate lobectomy, extrahepatic bile
      duct resection, and left hepaticojejunostomy were performed. The nodule was
      histologically diagnosed as papillary carcinoma in situ, and R0 resection was
      performed. However, mucus production from the papillary adenoma in the B3 and B4
      was observed. We carefully managed the patient's biliary tract by inserting a
      biliary drainage tube into the segment 2, and he has survived for more than 7
      years since the initial treatment. DISCUSSION: Mucus might be produced after the
      surgical resection of IPNB even if s surgical margin was benign. Five-year
      survival rate of benign IPNB was reported from 85% to 100%. That might be caused
      by difference of the postoperative management of the biliary tract. CONCLUSIONS:
      Careful management of the biliary tract should be performed after surgical
      resection of IPNB.

PMID- 28763697
TI  - Chronic inguinal pain after laparoscopic intraperitoneal onlay mesh (IPOM) repair
      for inguinal hernia treated successfully with laparoscopic selective neurectomy:
      A case report.
AB  - INTRODUCTION: Laparoscopic intraperitoneal onlay mesh (IPOM) repair is
      occasionally used for inguinal hernia repair. Here, we report a case of chronic
      neuropathic pain after laparoscopic IPOM repair for inguinal hernia, which was
      treated successfully with laparoscopic selective neurectomy. PRESENTATION OF
      CASE: A 59-year-old man with bilateral inguinal hernia underwent laparoscopic
      repair. Transabdominal preperitoneal repair was performed on the left side,
      whereas IPOM repair was performed on the right side due to a peritoneal defect.
      At postoperative month 1, he presented with severe pain and numbness distributed
      from the right inguinal region to the inner thigh region. The symptoms had
      persisted for 1year despite medical treatment. We diagnosed that the symptoms
      might be due to the entrapment of nerves in the contracted mesh, and performed a
      second surgery via laparoscopic approach 13 months after the first surgery. On
      laparoscopic exploration, the lateral side of the mesh was contracted and
      involved nerve branches. We ligated and cut off these nerve branches. His
      symptoms resolved immediately after the surgery. At postoperative month 12, he
      has passed without any pain, numbness, and hernia recurrence. DISCUSSION:
      Laparoscopic exploration would be useful to figure out chronic neuropathic pain
      after laparoscopic inguinal hernia repair. CONCLUSION: Laparoscopic IPOM repair
      for inguinal hernia should be avoided as much as possible because it may cause
      chronic neuropathic pain. Laparoscopic selective neurectomy is an option for
      patients with chronic neuropathic pain after laparoscopic hernia repair.

PMID- 28763698
TI  - Reducing effect of artichoke extract on heterocyclic aromatic amine formation in
      beef and chicken breast meat.
AB  - The aim of this study was to investigate the inhibitory effect of different
      levels of artichoke extract (0, 0.5, and 1.0%) on the formation of heterocyclic
      aromatic amines (HAAs) in beef and chicken breast meat cooked by either pan
      frying or oven-roasting. All meat samples were cooked at three different
      temperatures (150, 200, and 250 degrees C) and the levels of 12 HAAs (IQ, IQx,
      MeIQ, MeIQx, 4,8-DiMeIQx, 7,8-DiMeIQx, PhIP, harman, norharman, AalphaC,
      MeAalphaC, and Trp-P-2) were assessed. The total HAA content in beef and chicken
      breast ranged from not detectable to 49.26ng/g, and not detectable to 83.06ng/g,
      respectively. The inhibitory effects of 0.5 and 1.0% artichoke extracts on total
      HAAs levels were found to be 6-46% and 25-98% in beef, and 5-97% and 14-95% in
      chicken breast, respectively. The present study showed that artichoke extracts
      could mitigate HAA formation especially in oven-roasted beef and chicken breast
      meat.

PMID- 28763699
TI  - The use and control of nitrites in Serbian meat industry and the influence of
      mandatory HACCP implementation.

PMID- 28763700
TI  - Effect of dietary Tartary buckwheat extract supplementation on growth
      performance, meat quality and antioxidant activity in ewe lambs.
AB  - The objective of this study was to investigate the effect of dietary Tartary
      buckwheat extract (TBE) supplementation on animal growth performance, meat
      quality and antioxidative activity in the Longissimus thoracis et lumborum muscle
      of lambs. The results showed that dietary TBE increased body weight, average
      daily gain, carcass weight, dry matter intake, and digestive organ weight.
      Dietary TBE had no effect on the pH, color, shear force or intramuscular fat of
      Longissimus muscle examined, whereas the cooking loss was decreased. The total
      antioxidative capacity and glutathione peroxidase 4 (GPx4) activity of
      Longissimus muscle were increased in lambs fed TBE. The mRNA contents of
      superoxide dismutase, catalase, GPx4 and nuclear factor-like-2 factor (Nrf2) did
      not vary among the groups, and greater protein levels of GPx4 and Nrf2 were
      observed. Taken together, these results suggest that TBE can be used as a feed
      ingredient in lamb production to improve its growth performance, and relieve
      oxidative stress and increase water holding capacity of meat.

PMID- 28763701
TI  - Can family structure and social support reduce the impact of child victimization
      on health-related quality of life?
AB  - This study aims at providing a profile of the association between different types
      of child victimization and polyvictimization and health-related quality of life
      (HRQoL) among school-aged children, and examining the impact of family structure
      and social support on the negative health consequences associated with violent
      victimization. We conducted a cross-sectional school survey in Hong Kong using a
      two-stage stratified sampling procedure. The final sample comprised 4139
      children's self-reports and proxy-reports (boys=51.5%; mean age=6.3). The main
      outcome was HRQoL measured with the Pediatric Quality of Life Inventory (PedsQL).
      Family structure was represented by parents' marital status, major caregivers,
      number of siblings and the living arrangement of children. Child victimization,
      social support, and demographic characteristics were also measured. All types of
      child victimization were associated with compromised HRQoL, and the strength of
      association varied across different types of child victimization. Family
      structure (in particular the number of siblings and whether additional childcare
      was received from grandparents) and social support were associated with better
      HRQoL. The negative associations between child victimization and
      polyvictimization and HRQoL were reduced when there was an adjustment made for
      family structure and social support. Findings show that family structure and
      social support are related to a reduction in negative health consequences for
      child victimization. The varying strengths of negative associations between
      victimization and HRQoL highlight the possibility that the effects of child
      victimization on health might not be homogeneous.

PMID- 28763702
TI  - A wearable vibrotactile biofeedback system improves balance control of healthy
      young adults following perturbations from quiet stance.
AB  - Maintaining postural equilibrium requires fast reactions and constant adjustments
      of the center of mass (CoM) position to prevent falls, especially when there is a
      sudden perturbation of the support surface. During this study, a newly developed
      wearable feedback system provided immediate vibrotactile clues to users based on
      plantar force measurement, in an attempt to reduce reaction time and CoM
      displacement in response to a perturbation of the floor. Ten healthy young adults
      participated in this study. They stood on a support surface, which suddenly moved
      in one of four horizontal directions (forward, backward, left and right), with
      the biofeedback system turned on or off. The testing sequence of the four
      perturbation directions and the two system conditions (turned on or off) was
      randomized. The resulting reaction time and CoM displacement were analysed.
      Results showed that the vibrotactile feedback system significantly improved
      balance control during translational perturbations. The positive results of this
      preliminary study highlight the potential of a plantar force measurement based
      biofeedback system in improving balance under perturbations of the support
      surface. Future system optimizations could facilitate its application in fall
      prevention in real life conditions, such as standing in buses or trains that
      suddenly decelerate or accelerate.

PMID- 28763703
TI  - Multifractal foundations of visually-guided aiming and adaptation to prismatic
      perturbation.
AB  - Visually-guided action of tossing to a target allows examining coordination
      between mechanical information for maintaining posture while throwing and visual
      information for aiming. Previous research indicates that relationships between
      visual and mechanical information persist in tossing behavior long enough for
      mechanical cues to prompt recall of past visual impressions. Multifractal
      analysis might model the long-term coordinations among movement components as
      visual information changes. We asked 32 adult participants (6 female, 25 male,
      one not conforming to gender binary; aged M=19.77, SD=0.88) to complete an aimed
      tossing task in three blocks of ten trials each. Block 1 oriented participants to
      the task. Participants wore right-shifting goggles in Block 2 and removed them
      for Block 3. Motion-capture suits collected movement data of the head, hips, and
      hands. According to regression modeling of tossing performance, multifractality
      at hand and at hips together supported use of visual information, and adaptation
      to wearing/removing of goggles depended on multifractality across the hips, head,
      and hands. Vector-autoregression modeling shows that hip multifractality promoted
      head multifractality but that hand fluctuations drew on head and hip
      multifractality. We propose that multifractality could be an information
      substrate whose spread across the movements systems supports the perceptual
      coordination for the development of dexterity.

PMID- 28763704
TI  - Lifetime suicidal attempts and current suicidal risk in aging survivors of the
      Jeju April 3 incident.
AB  - BACKGROUND: The Jeju April 3 incident refer to a series of armed uprisings and
      counterinsurgency that occurred between 1948 and 1954 on Jeju Island, South
      Korea. These events resulted not only in an estimated 15,000-30,000 deaths but
      also in numerous casualties and the destruction of many villages on the island.
      We investigated the relationship between lifetime suicidal attempts, current
      suicidal risk, and exposure to the traumatic experiences associated with the Jeju
      April 3 incident. METHODS: The present study assessed the lifetime suicidal
      behaviors of 110 aging survivors of the Jeju April 3 incident and 492 community
      dwelling older adults who had not personally experienced this incident.
      Participants completed a questionnaire gathering demographic information and the
      Mini International Neuropsychiatric Interview (M.I.N.I.) items on suicidal
      ideation, suicide plans, and suicide attempts. To obtain information regarding
      depressive symptoms, we administered the Center for Epidemiologic Studies
      Depression Scale (CES-D). RESULTS: The prevalence rate for suicidal ideation
      within the past month in survivors was 42.7%, 95%CI [33.88, 52.07], and that in
      the comparison group was 15.4%, 95%CI [12.53, 18.91]. The survivor group reported
      higher rates of lifetime suicide attempts (8.2%, 95%CI [4.36, 14.82]) than the
      comparison group (2.0%, 95%CI [1.11, 3.70]). LIMITATIONS: The cross-sectional
      nature of the study design limits the interpretation of results. CONCLUSION:
      These findings suggest that the psychological consequences of the Jeju April 3
      incident, which occurred almost 70 years ago, may be long lasting. Our data can
      also contribute to interventions designed to prevent the development of serious
      psychological sequelae following traumatic events.

PMID- 28763705
TI  - Proteomic analysis of broccoli sprouts by iTRAQ in response to jasmonic acid.
AB  - Jasmonic acid (JA) is well known as a linolenic acid-derived signal molecule
      related to the plant response to biotic and abiotic stresses. JA can regulate
      various plant metabolisms, such as glucosinolate metabolism. In this study, the
      proteome profiles of broccoli sprouts under JA treatment were analyzed using the
      iTRAQ-based quantitative proteome approach. A total of 122 differentially
      expressed proteins participating in a wide range of physiological processes were
      confidently identified in broccoli sprouts treated with JA. Functional
      classification analysis showed that photosynthesis and protein synthesis were
      inhibited by JA treatment, thereby inhibiting sprout growth, while proteins
      related to carbohydrate catabolism and amino acid metabolism showed an increased
      expression. Additionally, proteins involved in defense and secondary metabolism
      were also up-regulated. Proteins related to glucosinolate biosynthesis and
      degradation were mediated by JA, leading to the accumulation of glucosinolates
      and sulforaphane. These results indicate that JA stimulated a defense response at
      the proteome level by redirecting metabolism of growth and physiology in broccoli
      sprouts.

PMID- 28763706
TI  - Variation in relative water content, proline accumulation and stress gene
      expression in two cowpea landraces under drought.
AB  - Many landraces of cowpea [Vigna unguiculata (L.) Walp.] are adapted to particular
      geographical and climatic conditions. Here we describe two landraces grown
      respectively in arid and temperate areas of Algeria and assess their
      physiological and molecular responses to drought stress. As expected, when
      deprived of water cowpea plants lose water over time with a gradual reduction in
      transpiration rate. The landraces differed in their relative water content (RWC)
      and whole plant transpiration rate. The landrace from Menia, an arid area,
      retained more water in adult leaves. Both landraces responded to drought stress
      at the molecular level by increasing expression of stress-related genes in aerial
      parts, including proline metabolism genes. Expression of gene(s) encoding proline
      synthesis enzyme P5CS was up regulated and gene expression of ProDH, a proline
      catabolism enzyme, was down regulated. Relatively low amounts of proline
      accumulated in adult leaves with slight differences between the two landraces.
      During drought stress the most apical part of plants stayed relatively turgid
      with a high RWC compared to distal parts that wilted. Expression of key stress
      genes was higher and more proline accumulated at the apex than in distal leaves
      indicating that cowpea has a non-uniform stress response at the whole plant
      level. Our study reveals a developmental control of water stress through
      preferential proline accumulation in the upper tier of the cowpea plant. We also
      conclude that cowpea landraces display physiological adaptations to water stress
      suited to the arid and temperate climates in which they are cultivated.

PMID- 28763707
TI  - Molecular cloning and functional characterization of a monoterpene synthase
      isolated from the aromatic wild shrub Thymus albicans.
AB  - The essential oil of Thymus albicans Hoffmanns. & Link, a native shrub from the
      Iberian Peninsula, is mainly composed of monoterpenes. In this study, a 1,8
      cineole synthase was isolated from the 1,8-cineole chemotype. A partial sequence
      that lacked the complete plastid transit peptide but contained an extended C
      terminal when compared to other related terpene synthases was generated by PCR
      and Rapid Amplification of cDNA Ends (RACE). The predicted mature polypeptide was
      593 amino acids in length and shared 78% and 77% sequence similarity with the
      homologue 1,8-cineole synthase from Rosmarinus officinalis and Salvia
      officinalis, respectively. The putative protein possessed the characteristic
      conserved motifs of plant monoterpene synthases including the RRx8W and DDxxD
      motifs and phylogenetic analysis indicated that the amplified 1,8-cineole
      synthase bears greater sequence similarity with other 1,8-cineole synthases from
      Lamiaceae family relative to the terpene synthases from the genus Thymus.
      Functional expression of the recombinant protein in Escherichia coli revealed
      that in the presence of geranyl diphosphate (GPP) 1,8-cineole was the major
      product but that its production was too low for robust quantification. Other
      minor conversion products included alpha-pinene, beta-pinene, sabinene and beta
      myrcene suggesting the isolated 1,8-cineole synthase may be a multi-product
      enzyme. To our knowledge, this is the first report of a functionally
      characterized monoterpene synthase from Thymus albicans.

PMID- 28763708
TI  - Sensory role of actin in auxin-dependent responses of tobacco BY-2.
AB  - Polar auxin transport depends on the polar localization of auxin-efflux carriers.
      The cycling of these carriers between cell interior and plasma membrane depends
      on actin. The dynamic of actin not only affects auxin transport, but also changes
      the auxin-responsiveness. To study the potential link between auxin
      responsiveness and actin dynamics, we investigated developmental responses of the
      non-transformed BY-2 (Nicotiana tabacum L. cv Bright Yellow 2) cell line and the
      transgenic BY-2 strain GF11 (stably transformed BY-2 cells with a GFP-fimbrin
      actin-binding domain 2 construct). The developmental process was divided into
      three distinct stages: cell cycling, cell elongation and file disintegration.
      Several phenotypes were measured to monitor the cellular responses to different
      concentrations of exogenous natural auxin (Indole-3-acetic acid, IAA). We found
      that auxin stimulated and prolonged the mitotic activity, and delayed the exit
      from the proliferation phase. However, both responses were suppressed in the GF11
      line. At the stationary phase of the cultivation cycle, auxin strongly
      accelerated the cell file disintegration. Interestingly, it was not suppressed
      but progressed to a more complete disintegration in the GF11 line. During the
      cultivation cycle, we also followed the organization of actin in the GF11 line
      and did not detect any significant difference in actin organization from
      untreated control or exogenous IAA treatment. Therefore, our findings indicate
      that the specific differences observed in the GF11 line must be linked with a
      function of actin that is not structural. It means that there is a sensory role
      of actin for auxin signaling.

PMID- 28763709
TI  - Similar mechanisms of traumatic rectal injuries in patients who had anal sex with
      animals to those who were butt-fisted by human sexual partner.
AB  - Sexual pleasure comes in various forms of physical play, for many it involves
      stimulation of the vagina, while the anus for others; some enjoy both. A recent
      report by Cappelletti et al.1 shows a meta-analysis of cases describing anal
      trauma due to sexual fisting in human partners. This clinical article reports
      four cases of males diagnosed with zoophilia, and who received anal sex from
      animals, resulting in injuries. Surgical and psychiatric evaluations are
      summarized. Unusual etiology of sexual activity with animals caused peri-anal
      trauma in men who engaged in anal sex with dogs and farm animals. Injuries to
      patients who receive anal sex from animals are mechanistically similar to fisting
      induced rectal damage. Among zoophiles, the mode of harm occurs through blood
      engorged, interlocked penis that causes tissue lacerations upon retraction from
      an anus. In people experimenting with fisting, repetitive stretching within anal
      canal and of external sphincter causes the internal injuries. The mode of
      physical stimulation explains the extent of injuries in fisters vs. zoophiles: in
      fisting, the pressure applied by hand is controllable proximally around and
      within anal sphincter, while penetration by the animal penis is unpredictable and
      occurs within the proximal anal canal. Forensically, the findings presented in
      this article describe a significant mechanism of injury in fisters versus passive
      zoophiles. These descriptions may aid in clinically differentiating pleasurable
      and pathological rectal stimulation.

PMID- 28763710
TI  - Osteoarchaeological evidence of an unknown medieval battle in Northern Italy. A
      case of Forensic Anthropology.

PMID- 28763711
TI  - What do clinicians understand about deaths reportable to the Coroner?
AB  - SETTING: The study setting is a tertiary referral hospital of over 980 beds, in
      Victoria, Australia. The hospital is a long established major academic public
      health service providing healthcare, health professional education and health
      research. The hospital has 103,756 in-patient admissions, 190,756 outpatient
      attendances and over 82,000 presentations to the Emergency Department annually.
      PARTICIPANTS: 22 clinicians completed an in-depth, audio-recorded interview: 12
      medical and 10 nursing staff, with a variety of clinical experience.
      INTERVENTION(S): Each audio recorded interview was transcribed verbatim for
      thematic analysis. The semi structured questions were designed to explore the
      clinician's understanding of deaths that meet the criteria to be reported to
      Coroners Court of Victoria (CCOV), and why such reporting was required. There was
      also the opportunity to identify any barriers or enablers to the reporting
      process, whether internal or external to the organisation. RESULTS: Two main
      themes emerged from the interviews: 1. lack of awareness of which deaths are
      reportable to the coroner and 2. the need for educational support. Several
      subthemes were also identified such as accountability, the need for feedback and
      blame. DISCUSSION: The understanding of clinicians as to which deaths meet the
      reportable criteria in healthcare is quite variable and this indicates that there
      might be a level of under reporting. Apart from the potential of not meeting
      legal obligations, there may also be the loss of a valuable opportunity for
      lessons to inform clinical practice and enhance the delivery of safe patient
      care.

PMID- 28763712
TI  - Crossover study of amputee stair ascent and descent biomechanics using Genium and
      C-Leg prostheses with comparison to non-amputee control.
AB  - This study was a randomized crossover of stair ambulation of Transfemoral
      Amputees (TFAs) using the Genium and C-Leg prosthetic knees. TFAs typically have
      difficulty ascending and descending stairs, limiting community mobility. The
      objective of this study was to determine the relative efficacy of the Genium and
      C-Leg prostheses for stair ascent and descent, and their absolute efficacy
      relative to non-amputees. Twenty TFAs, and five non-amputees participated in the
      study. TFAs were randomized to begin the study with the Genium or C-Leg
      prosthesis. Informed consent was obtained from all participants prior to data
      collection and the study was listed on clinicaltrials.gov (#NCT01473662). After
      fitting, accommodation, and training, participants were asked to demonstrate
      their preferred gait pattern for stair ascent and descent and a step-over-step
      pattern if able. TFAs then switched prosthetic legs and repeated fitting,
      accommodation, training, and testing. An eight camera Vicon optical motion
      analysis system, and two AMTI force plates were used to track and analyze the
      participants' gait patterns, knee flexion angles, knee moment normalized by body
      weight, and swing time. For stair descent, no significant differences were found
      between prostheses. For stair ascent, Genium use resulted in: increased ability
      to use a step-over-step gait pattern (p=0.03), increased prosthetic side peak
      knee flexion (p<0.01), and increased swing duration (p<0.01). Changes in
      contralateral side outcomes and in knee moment were not significant. Overall the
      Genium knee decreased deficiency in gait patterns for stair ascent relative to
      the C-Leg, by enabling gait patterns that more closely resembled non-amputees.

PMID- 28763713
TI  - Spatiotemporal and plantar pressure patterns of 1000 healthy individuals aged 3
      101 years.
AB  - OBJECTIVE: The purpose of this study was to establish normative reference values
      for spatiotemporal and plantar pressure parameters, and to investigate the
      influence of demographic, anthropometric and physical characteristics. METHODS:
      In 1000 healthy males and females aged 3-101 years, spatiotemporal and plantar
      pressure data were collected barefoot with the ZenoTM walkway and Emed(r)
      platform. Correlograms were developed to visualise the relationships between
      widely reported spatiotemporal and pressure variables with demographic (age,
      gender), anthropometric (height, mass, waist circumference) and physical
      characteristics (ankle strength, ankle range of motion, vibration perception) in
      children aged 3-9 years, adolescents aged 10-19 years, adults aged 20-59 years
      and older adults aged over 60 years. RESULTS: A comprehensive catalogue of 31
      spatiotemporal and pressure variables were generated from 1000 healthy
      individuals. The key findings were that gait velocity was stable during
      adolescence and adulthood, while children and older adults walked at a comparable
      slower speed. Peak pressures increased during childhood to older adulthood.
      Children demonstrated highest peak pressures beneath the rearfoot whilst
      adolescents, adults and older adults demonstrated highest pressures at the
      forefoot. Main factors influencing spatiotemporal and pressure parameters were:
      increased age, height, body mass and waist circumference, as well as ankle
      dorsiflexion and plantarflexion strength. CONCLUSION: This study has established
      whole of life normative reference values of widely used spatiotemporal and
      plantar pressure parameters, and revealed changes to be expected across the
      lifespan.

PMID- 28763714
TI  - Muscle contributions to knee extension in the early stance phase in patients with
      knee osteoarthritis.
AB  - The aim of this study was to analyze individual muscle contributions to knee
      angular acceleration using a musculoskeletal simulation analysis and evaluate
      knee extension mechanics in the early stance phase in patients with knee
      osteoarthritis (OA). The subjects comprised 15 patients with medial knee OA and
      14 healthy elderly individuals. All participants underwent gait performance test
      using 8 infrared cameras and two force plates to measure the kinetic and
      kinematic data. The simulation was driven by 92 Hill-type muscle-tendon units of
      the lower extremities and a trunk with 23 degrees  of freedom. We analyzed each
      muscle contribution to knee angular acceleration in the 5%-15% and 15%-25%
      periods of the stance phase (% SP) using an induced acceleration analysis. We
      compared accelerations by individual muscles between the two groups using an
      analysis of covariance for controlling gait speed. Patients with knee OA had a
      significantly lesser knee extension acceleration by the vasti muscles and higher
      knee acceleration by hip adductors than those in controls in 5-15% SP. In
      addition, knee OA resulted in significantly lesser knee extension acceleration by
      the vasti muscles in 15-25% SP. These results indicate that patients with knee OA
      have decreased dependency on the vasti muscles to control knee movements during
      early stance phase. Hip adductor muscles, which mainly control mediolateral
      motion, partly compensate for the weak knee extension by the vasti muscles in
      patients with knee OA.

PMID- 28763715
TI  - Adding an arch support to a heel lift improves stability and comfort during gait.
AB  - Heel lifts have been widely used as a conservative treatment for some
      musculoskeletal problems and complaints. However, the heel rise caused by heel
      lifts may also affect the plantar pressure distribution and stability during
      walking. This study aimed to test whether adding an arch support to a heel lift
      would improve its stability and comfort through comparing the center of pressure
      (COP) during walking and subjective ratings between heel lifts with and without
      an arch support. Fifteen healthy male participants were asked to walk along an 8m
      walkway while wearing high-cut footwear with the control heel lifts and the heel
      lifts with an arch support. A Footscan pressure plate was used to measure the COP
      during walking. Subjective ratings including medial-lateral control, dynamic
      foot/shoe fitting and overall comfort were assessed for each participant. The
      results showed that compared to the control condition, the COP trajectory was
      medially shifted during stance phase of gait in the arch support condition. The
      maximum displacements and velocity of medial-lateral COP in the forefoot contact
      phase were smaller in the arch support condition than in the control condition.
      Adding an arch support to a heel lift also significantly improved the subjective
      ratings in terms of the medial-lateral control, dynamic foot/shoe fitting and
      overall comfort. The findings of this study suggest that adding an arch support
      to a heel lift could improve its stability and comfort during walking.

PMID- 28763716
TI  - In-situ force plate calibration: 12 years' experience with an approach for
      correcting the point of force application.
AB  - Force plates are common assessment tools used in biomechanics to measure ground
      reaction forces during motion capture or strength exercises. While the accuracy
      of the resulting kinetic data is critical for accurate gait analysis, factors
      such as plate mounting are thought to influence the measured point of force
      application (PFA) of the ground reaction forces. The aim of this study was
      therefore to present an accurate in-situ PFA calibration method. In addition, the
      approach was evaluated by examining the required PFA corrections over a period of
      ten years, which included plate remounting and a change of foundation. The in
      situ PFA calibration was performed on six plates by assessing the locations of up
      to 98 points of force application per plate using an instrumented pole.
      Application of the in-situ PFA calibration approach reduced the root mean square
      errors by up to approximately 60% compared to the manufacturers calculation.
      Correction coefficients were strongly dependent on the individual platform as
      well as the location of the applied force on the plate. Remounting of the plates
      altered the plate coefficient corrections considerably, while changes over time
      were notable but not as extensive. We therefore recommend that plates should be
      recalibrated after remounting, but also at least every 5 years, in order to
      ensure the preservation of an accurate PFA.

PMID- 28763717
TI  - Regional decrease in gray matter volume is related to body dissatisfaction in
      anorexia nervosa.
AB  - Anorexia nervosa (AN) is a psychiatric disorder, in which the prognosis for some
      patients is poor. The etiology and effective treatments for AN have not been
      established. We examined morphometric changes in the brain of AN and clarified
      how the changes were associated with symptoms and pathophysiology. We enrolled 52
      participants: 7 with the restrictive type of AN, 13 with the binge-eating/purging
      type, 3 with eating disorder not otherwise specified, and 29 healthy controls.
      Participants underwent T1-weighted MRI. Group differences between patients and
      controls in gray matter volume (GMV) were analyzed using voxel-based morphometry.
      Age and body mass index (BMI) were considered covariates. Correlations between
      regional GMVs and drive for thinness and body dissatisfaction were examined.
      Patients had decreased GMV in the superior/middle temporal gyrus (STG/MTG),
      pulvinar, and superior frontal gyrus after correction for age and BMI, and in the
      STG/MTG, middle frontal gyrus, and cingulate after correction for age. A
      correlational group difference was detected for body dissatisfaction and GMV in
      the STG. Our findings suggest that decreased GMV in the STG is related to body
      dissatisfaction that could come from impaired visuospatial perception, together
      with GMV decreases in several regions, which may be involved in development of
      AN.

PMID- 28763718
TI  - Lifetime PTSD and geriatric depression symptomatology relate to altered
      dorsomedial frontal and amygdala morphometry.
AB  - Posttraumatic stress disorder (PTSD) affects a large portion of combat deployed
      Veterans. Moreover, many individuals also suffer from comorbid late life
      depression (geriatric depression; GD). While a great deal of research has begun
      to characterize the morphometric features of PTSD and depression individually,
      few studies have investigated the interacting effect of these two disorders,
      specifically in a Veteran population. The current study used cortical and
      subcortical surface-based morphometry (SBM) in combination with psychological
      assessments of PTSD and GD symptom severity to examine morphometric alterations
      in Vietnam War Veterans. Our results indicated that increased GD severity, PTSD
      symptomatology, and their interaction, was related to decreased grey matter
      volume (GMV) in the left dorsomedial prefrontal cortex (dmPFC). Furthermore,
      increased symptomatology in the PTSD subscales of reexperiencing and hyperarousal
      were additionally found to be related to decreased GMV in this same dmPFC region.
      Subcortically, the interacting effect between PTSD and GD was also significantly
      related to regional shape variation in the left amygdala. These results suggest
      that morphometry of cortical (dmPFC) and non-neocortical regions (amygdala)
      putatively underlying emotional reactivity and the emotional components of memory
      is altered in PTSD and GD.

PMID- 28763719
TI  - Dynamic responses of antioxidant enzymes in pearl oyster Pinctada martensii
      exposed to di(2-ethylhexyl) phthalate (DEHP).
AB  - Di(2-ethylhexyl) phthalate (DEHP) is recognized as one of the most ubiquitous
      contaminants in marine environments and causes adverse effects on the health of
      marine organisms. The purpose of this study was to investigate the toxic effects
      of DEHP on the pearl oyster Pinctada martensii. The Pinctada martensii was
      exposed to 0.0, 0.5, 2, 8, or 32mgL-1 DEHP for 7 and 10days using parameters of
      antioxidant. Antioxidant indicators included levels of superoxide dismutase
      (SOD), catalase (CAT), glutathione (GSH), peroxidase (POD), and total antioxidant
      capacity (T-AOC) in the gills and hepatopancreas of Pinctada martensii for 7 and
      10days. Besides, we used the lowest observed effect concentration (LOEC) of five
      enzyme activities in different tissues of Pinctada martensii for 7 and 10days to
      compare sensitivity. The results showed that the gills were more sensitive than
      the hepatopancreas of Pinctada martensii and that GSH activity in the gills and
      CAT activity in the hepatopancreas might be suitable biomarkers after 7days of
      DEHP exposure. After 10days of DEHP exposure, the GSH activity and CAT activity
      in the gills and SOD activity in the hepatopancreas could be regarded as
      biomarkers. Compared to the LOEC, GSH activity in the gills and CAT activity in
      the hepatopancreas after 7days of DEHP exposure were more sensitive than any
      other biomarkers. In addition, after 10days of DEHP exposure, GSH activity in the
      gills and hepatopancreas were much more sensitive than other activities. In
      conclusion, GSH activity demonstrated its potential to be used as a biomarker for
      the monitoring of DEHP pollution in the marine environment.

PMID- 28763720
TI  - Increasing the uptake of long-acting and permanent methods of family planning: A
      qualitative study with village midwives in East Java and Nusa Tenggara Barat
      Provinces, Indonesia.
AB  - OBJECTIVE: this analysis aims to explore midwives' insights into the provision of
      long-acting and permanent methods of contraception (LAPMs) in the selected areas
      of East Java and Nusa Tenggara Barat (NTB) Provinces, Indonesia. DESIGN: a
      qualitative study using in-depth interviews was conducted with 12 village
      midwives from 12 villages, to explore their perceptions and experiences in
      delivering family planning services. SETTING: the study was carried out in May
      June 2013, as part of the baseline assessment in the Improving Contraceptive
      Method Mix (ICMM) study. We interviewed 12 village midwives working in 12
      villages in six study districts: Tuban, Kediri, and Lumajang Districts in East
      Java Province; and Lombok Barat, Lombok Timur, and Sumbawa Districts in NTB
      Province. MEASUREMENT: an interview guideline was used in all interviews. It
      covered several topics, such as community perceptions of LAPMs, availability of
      contraception and related equipment, availability of human resources, and
      midwives' efforts to improve LAPM coverage. All interviews were recorded and
      transcribed. Content and thematic analyses were carried out by grouping and
      coding the information based on the identified themes and topics. FINDINGS:
      according to village midwives interviewed in this study, community-level
      acceptance of LAPMs has increased over time; however, some still prefer using
      short-acting methods for a long period. The reasons include lack of awareness
      about the benefits and side effects of LAPMs, fear of surgical procedures,
      rumored consequences (for example, that LAPMs would limit women's ability to
      perform hard physical labor), and religious beliefs. There were several
      challenges reported by village midwives in delivering LAPM services, such as
      confusion about midwives' eligibility to provide LAPM services, lack of
      Contraceptive Technology Update (CTU) and counseling trainings, and shortage of
      supporting equipment (such as exam tables and IUD and implant insertion kits).
      There were several strategies implemented by village midwives to improve LAPM
      use, including strengthening the counseling services, accompanying clients to
      higher health facilities to obtain LAPM services, and providing services for
      groups of clients. All village midwives emphasized the importance of
      strengthening collaboration among stakeholders to increase the uptake of LAPM
      services. KEY CONCLUSIONS: as midwives are the main family planning providers in
      Indonesia, efforts to address their challenges is essential. Enabling a
      supportive policy environment, strengthening promotional activities, increasing
      the number of training programs designed for village midwives-in addition to
      enhancing inter-sectoral collaboration-are some recommendations to improve LAPM
      uptake in study areas.

PMID- 28763721
TI  - Women's experiences of routine care during labour and childbirth and the
      influence of medicalisation: A qualitative study from Iran.
AB  - OBJECTIVE: to understand women's experiences of routine care during labor and
      childbirth in a medicalised context. DESIGN: twenty-six in-depth interviews were
      conducted during the late postpartum period and thematic analysis was applied.
      SETTING: four public hospitals in Tehran with a high rate of births, providing
      services to low and middle income families. PARTICIPANTS: women who had a low
      risk pregnancies and gave a birth to a healthy infant by normal vaginal delivery.
      FINDINGS: two main themes emerged: 'An ethos of medicalisation' which indicates
      that women's perception of childbirth was influenced by the medicalised context
      of childbirth. And 'The reality of fostered medicalisation' which illustrates the
      process by which interventions during labor affected women's pathway through
      childbirth, and how the medicalisation resulted in a birth experience which often
      included a preference for Caesarean Section rather than vaginal birth with
      multiple interventions. IMPLICATIONS FOR PRACTICE: contextual factors such as
      legal issues, state's regulations and the organisational framework of maternity
      services foster medicalised childbirth in Tehran public hospitals. These factors
      influence the quality of care and should be considered in any intervention for
      change. The aim should be a high quality birth experience with minimal
      interventions during normal vaginal delivery. A midwifery model of care combining
      scientific evidence with empathy may address this need for change.

PMID- 28763722
TI  - Glutamate metabolism in temporal lobe epilepsy as revealed by dynamic proton MRS
      following the infusion of [U13-C] glucose.
AB  - Focal metabolic dysfunction commonly observed in temporal lobe epilepsy (TLE),
      and is associated with the development of medical intractability and
      neurocognitive deficits. It has not been established if this dysfunction is due
      to cell loss or biochemical dysfunction in metabolic pathways. To explore this
      question, dynamic 1H MRS following an infusion of [U13- C] glucose was performed
      to measure glutamate (Glu) metabolism. Subjects (n=6) showed reduced Glu levels
      (p<0.01) in the ipsilateral mesial temporal lobe (MTL) compared with controls
      (n=4). However, the rate of 13C incorporation into Glu did not differ between
      those with epilepsy and controls (p=0.77). This suggests that reduced Glu
      concentrations in the region of the seizure focus are not due to disruptions in
      metabolic pathways, but may instead be due to neuronal loss or simplification.

PMID- 28763723
TI  - Validity of self-reported cancer history in the health examinees (HEXA) study: A
      comparison of self-report and cancer registry records.
AB  - PURPOSE: To assess the validity of the cohort study participants' self-reported
      cancer history via data linkage to a cancer registry database. METHODS: We
      included 143,965 participants from the Health Examinees (HEXA) study recruited
      between 2004 and 2013 who gave informed consent for record linkage to the Korean
      Central Cancer Registry (KCCR). The sensitivity and the positive predictive value
      of self-reported histories of cancer were calculated and 95% confidence intervals
      were estimated. RESULTS: A total of 4,860 participants who had at least one
      record in the KCCR were included in the calculation of sensitivity. In addition,
      3,671 participants who reported a cancer history at enrollment were included in
      the calculation of positive predictive value. The overall sensitivity of self
      reported cancer history was 72.0%. Breast cancer history among women showed the
      highest sensitivity (81.2%), whereas the lowest sensitivity was observed for
      liver cancer (53.7%) and cervical cancer (52.1%). The overall positive predictive
      value was 81.9%. The highest positive predictive value was observed for thyroid
      cancer (96.1%) and prostate cancer (96.1%), and the lowest was observed for
      cervical cancer (43.7%). CONCLUSION: The accuracy of self-reported cancer history
      varied by cancer site and may not be sufficient to ascertain cancer incidence,
      especially for cervical and bladder cancers.

PMID- 28763724
TI  - Ovarian dynamics and estrous cycle length in the donkey (Equus asinus).
AB  - Nine jennies were monitored daily by ultrasonography during three complete
      ovarian cycles in order to evaluate if the timing of luteolysis and the growth
      pattern of the ovulatory follicle (OVF) before, during and after luteolysis are
      related to the length of the interovulatory interval (IOI). Blood samples for
      progesterone determination were obtained daily during one of the cycles of each
      jenny. The cycles were classified according to the length of the IOI into three
      groups: Short IOI (21.2 +/- 0.3 d, n = 10), medium IOI (23.9 +/- 0.4 d, n = 7),
      and long IOI (26.2 +/- 0.3 d, n = 10). Neither the time of luteolysis onset nor
      the time of luteolysis completion were significantly different between groups.
      The length of the IOI was mainly determined by the duration of the follicular
      phase, as the intervals from luteolysis onset to ovulation and from luteolysis
      completion to ovulation were directly correlated with the length of the IOI (p <
      0.001 and p < 0.01 respectively). Multiple regression analysis revealed that the
      length of the IOI was negatively correlated with the size of the OVF at day 13 (p
      < 0.01), with its growth rate from day 13 to day 15 (p < 0.05) and with its
      growth rate from day 15 to day 18 (p < 0.01), and positively correlated with the
      final diameter of the OVF (p < 0.01). The correlation between the observed IOIs
      and those predicted by the multiple regression equation was highly significant (r
      = 0.91, p < 0.001), but the predictive ability of a simplified equation using
      only the diameter of the OVF at day 18 was almost as good (r = 0.89, p < 0.001).
      Estrus signs lasted longer and were more intense as the length of the IOI
      increased, and this was associated with a longer period of low progesterone
      concentrations during the follicular phase of jennies with longer cycles. It is
      concluded that the length of the luteal phase in jennies is relatively constant,
      and that most of the variation in the length of the IOI is associated with
      differences in the size of the OVF at the time of luteolysis onset and with its
      growth rate during the following five days.

PMID- 28763725
TI  - Peroxidized mineral oil increases the oxidant status of culture media and
      inhibits in vitro porcine embryo development.
AB  - The use of oils with undetected alterations is a long-recognized problem for in
      vitro embryo production systems. Since peroxides in oils have been associated
      with reduced embryo production outcomes, our goals were (1) to evaluate the
      effects of a batch of mineral oil (MO) that was suspected to be altered on the in
      vitro production of pig embryos and (2) to determine oil peroxide values
      throughout culture and the transfer of oxidant agents from oil to culture media.
      Sunflower oil, which has a completely different chemical composition than MO but
      a higher oxidative status, and unaltered MO were used as controls. Oocyte
      maturation, fertilization and embryo development were affected differently
      depending on the oil overlay used. While the suspected MO was not able to sustain
      in vitro maturation and fertilization, the oocytes incubated in the presence of
      sunflower oil were matured and fertilized similarly to those of the unaltered MO
      group. Moreover, the cleavage rate of presumed zygotes cultured under the
      suspected MO was severely reduced compared with those cultured under the other
      oils, and none of the cleaved embryos developed to the blastocyst stage. Although
      the cleavage rates in the sunflower oil and unaltered MO groups were similar,
      embryos cultured under sunflower oil also failed to develop to the blastocyst
      stage. Our results revealed that the suspected MO and sunflower oil had similar
      levels of peroxides and that these levels were much higher than those of the
      unaltered MO. The total oxidant status was higher in media incubated under
      peroxidized oils than in fresh media or media incubated without an oil overlay or
      under unaltered MO, indicating that oxidant agents were transferred to the
      incubation media. However, unlike the sunflower oil group, the culture media
      incubated under the suspected MO had high levels of total oxidant status and low
      levels of hydrogen peroxide and reactive oxygen species, suggesting the presence
      of other unknown oxidant agents in that oil. These results indicate that a
      peroxidized MO overlay dramatically decreases embryo production outcomes. This
      decrease could be associated with the higher peroxide values of the oil but
      cannot be explained by the levels of hydrogen peroxide and reactive oxygen
      species transferred from the oil to the culture media. It is likely that
      different oxidant agent(s) and/or other toxic compounds present in the
      peroxidized MO are responsible for its damaging effects on oocytes and embryos.

PMID- 28763727
TI  - The effect of stillbirth on reproductive and productive performance of pure
      Egyptian buffaloes and their crosses with Italian buffaloes.
AB  - High rates of stillbirth in buffaloes are not only emotionally and economically
      undesirable but also contrary to animal welfare practices. Thus, this study was
      aimed to investigate risk factors for stillbirth and analyze its effects on the
      productive and reproductive performance of pure Egyptian buffaloes (PE) and their
      crossing with the Italian buffaloes (F1 crosses 50%PE and 50%Italian buffaloes
      and Back cross (BC) 75%PE and 25%Italian buffaloes) under subtropical
      environmental conditions. Records of a total of 8388 (5169PE, 1494F1 and 1725BC)
      were used in this study with 1965 actual first parity records (489, 621 and 855,
      respectively). The incidence of stillbirth in the farms was 12.4% and 9.2% for
      primiparous and multiparous cows, respectively. It did not vary among seasons or
      due to gestation length, calf sex and conception after first insemination in BC
      buffaloes. BC buffaloes with stillbirths had shorter gestation length, first
      service post-partum and longer dry period (300.32, 33.67 and 207.05days,
      respectively) compared to those live births (311.28, 33.90 and 140.22days,
      respectively), implying that these animals could better adapt to the tough
      circumstances following stillbirth as reproductive indices were only slightly
      affected due to stillbirths. Contrarily, the productivity and reproductive
      performance of PE buffaloes were markedly decreased after stillbirth. Their milk
      yield, average daily milk yield and lactation length were decreased by 6.27,
      10.29 and 6.36%, respectively after stillbirth, while days open, dry period and
      first service post-partum were increased after stillbirth by 14.28, 13.54 and
      12.78%, respectively. The results from this study suggest that producers should
      be promoted to increase the BC animals in their farms with the intention of
      increasing milk production and ensure superior reproduction efficiencies with
      lower stillbirth incidence.

PMID- 28763726
TI  - Effect of different hormonal combinations on follicular wave emergence and
      superovulatory response in sheep.
AB  - The aim of the present study was to compare hormonal treatments to induce and
      synchronize follicular wave emergence to improve the results of superovulatory
      (SOV) treatments in ewes. In Experiment 1 (n = 66), ewes were treated with a
      progesterone intravaginal implant plus a PGF2alpha analogue (group GP4), or with
      the same treatment plus estradiol benzoate (GP4+EB), a GnRH agonist (GP4+GnRH),
      or both, estradiol benzoate and a GnRH agonist (GP4+EB+GnRH) in a 2 * 2 factorial
      arrangement. Follicular wave emergence was determined by ultrasound. Follicular
      wave did not emerge during the studied period in 10 females (one from GP4, six
      from GP4+EB and three from GP4+EB+GnRH). Follicular emergence was less
      synchronized (P = 0.007) when estradiol was administered (GP4+EB: 103.6 +/- 22.0
      h), without any interaction with GnRH treatment (GP4+EB+GnRH: 80.1 +/- 21.4 h,
      GP4+GnRH: 52.5 +/- 8.7 h, GP4: 56.6 +/- 10.4 h). Estradiol administration delayed
      the moment of follicular emergence (P = 0.007) and the follicular wave emergence
      moment in which follicular dominance was achieved (P = 0.009), without
      interactions between estradiol and GnRH in the moment of follicular wave
      emergence or dominance. In Experiment 2 (n = 22), two SOV protocols were
      compared: the best treatment of Experiment 1 (GP4) was used to synchronize
      follicular wave emergence, initiating the SOV treatment 2.5 days later; in the
      control treatment, SOV treatment started 80 h after a short-term protocol to
      synchronize ovulation (Gcontrol). The number of corpora lutea (CL) and the
      evaluation of the collected embryos were performed six days after estrus. Blood
      samples were collected daily for plasma progesterone determination. Although the
      number of CL was similar in Gcontrol (7.1 +/- 1.0) and GP4 (6.9 +/- 5.1), the
      number of structures and viable embryos recovered were greater in Gcontrol (P <
      0.05). The occurrence of luteal premature regression was significantly greater in
      GP4 (60%) than in Gcontrol (8.3%). The use of GnRH agonist alone did not improve
      synchronization of follicular wave emergence. When EB was used (alone or
      associated) follicular wave emergence was less synchronized. The SOV protocol
      proposed had a similar ovarian response; however, it resulted in less
      transferable embryos.

PMID- 28763728
TI  - Crural Index and extensive atherosclerosis of crural vessels are associated with
      long-term cardiovascular mortality in patients with symptomatic peripheral artery
      disease.
AB  - BACKGROUND AND AIMS: Limited data exist on the association of the anatomical
      distribution of atherosclerotic lesions and the extent of atherosclerosis at
      defined arterial segments with life expectancy. We recently presented a new
      classification of the extent of atherosclerosis in crural vessels and showed that
      Crural Index (CIx) was associated with mid-term survival of symptomatic
      peripheral artery disease (PAD) patients. This study evaluates the significance
      of the extent of crural atherosclerosis on long-term cardiovascular mortality.
      METHODS: 887 consecutive patients with PAD, admitted for digital subtraction
      angiography (DSA) at Turku University Hospital Department of Vascular Surgery
      (Turku, Finland) between January 1st, 2009 and July 30th, 2011, were
      retrospectively analysed. Each crural angiographic image was graded according to
      CIx criteria. Aorto-iliac and femoro-popliteal arterial segments were similarly
      graded according to modified TASC II criteria. CIx was used as the categorical
      variable for the extent of atherosclerosis in crural vessels for survival
      analysis. Survival was also evaluated with respect to which arterial segment was
      most severely affected. Causes of death were provided by the Cause of Death
      Registry of Statistics Finland, updated on January 23rd, 2017. RESULTS:
      Altogether, 408 (46%) patients died during follow-up. The majority of deaths were
      due to cardiovascular causes (n = 246, 60%). Cardiovascular mortality was
      strongly associated with a high CIx (CIx III (Hazard ratio (HR) 2.16, Confidence
      interval (CI) 95% 1.23-3.80, p = 0.007)) and CIx IV (HR 3.513, 95% CI 1.93-4.565,
      p < 0.001), as compared to CIx 0. In patients having the crural segment as the
      most severely affected arterial segment, cardiovascular mortality was
      significantly increased (HR 2.321, 95% CI 1.45-3.73, p < 0.001), as was overall
      mortality (HR 2.177, 95% CI 1.53-3.10, p < 0.001). CONCLUSIONS: High Crural Index
      and extensive crural vessel atherosclerosis are associated with long-term
      cardiovascular mortality, and both may serve as useful indicators of survival
      among patients with symptomatic PAD.

PMID- 28763729
TI  - An evaluation of clinical performance of FTA cards for HPV 16/18 detection using
      cobas 4800 HPV Test compared to dry swab and liquid medium.
AB  - BACKGROUNDS: Effective dry storage and transport media as an alternative to
      conventional liquid-based medium would facilitate the accessibility of women in
      the low-resource settings to human papillomavirus (HPV)- based cervical cancer
      screening. OBJECTIVE: To evaluate analytical and clinical performance of
      indicating FTATM Elute Cartridge (FTA card) for the detection of HPV16/18 and
      cervical precancerous lesions and cancer compared to dry swab and liquid medium.
      STUDY DESIGN: Ninety patients with abnormal cytology and/or HPV infection were
      included for analysis. Three specimens of cervical exfoliated cells from each
      woman were randomly collected by FTA card, dry swab or liquid-based medium prior
      to colposcopy examination. The subsequent HPV DNA tests were performed on cobas
      4800 HPV platform. RESULTS AND CONCLUSIONS: High-risk HPV (hrHPV) positivity rate
      was 63.3%, 62.2% and 65.6% for samples collected by FTA card, dry swab and liquid
      medium, respectively. The overall agreements and kappa values for the detection
      of hrHPV, HPV 16 and HPV 18 between FTA card and liquid-based medium were 88.9%
      (kappa=0.76), 97.8% (kappa=0.94) and 100% (kappa=1.0),respectively; between FTA
      card and dry swab were 92.1% (kappa=0.83), 94.5% (kappa=0.87) and 100%
      (kappa=1.0), respectively. The performances of hrHPV tested by FTA card, dry
      swab, and liquid-based medium for detecting CIN2+ were comparable in terms of the
      sensitivity and specificity. The specificity of detection of CIN2+ by HPV16/18
      increased by approximately 40% compared to hrHPV for any medium albeit at cost of
      a moderate loss of sensitivity. Dry medium might offer an alternative to
      conventional liquid-based medium in the HPV-based cervical cancer screening
      program especially in low-resource settings but still needs further evaluation.

PMID- 28763731
TI  - Natural Assurance Scheme: A level playing field framework for Green-Grey
      infrastructure development.
AB  - This paper proposes a conceptual framework to systematize the use of Nature-based
      solutions (NBS) by integrating their resilience potential into Natural Assurance
      Scheme (NAS), focusing on insurance value as corner stone for both awareness
      raising and valuation. As such one of its core goal is to align research and
      pilot projects with infrastructure development constraints and priorities. Under
      NAS, the integrated contribution of natural infrastructure to Disaster Risk
      Reduction is valued in the context of an identified growing need for climate
      robust infrastructure. The potential of NAS benefits and trade-off are explored
      by through the alternative lens of Disaster Resilience Enhancement (DRE). Such a
      system requires a joint effort of specific knowledge transfer from research
      groups and stakeholders to potential future NAS developers and investors. We
      therefore match the knowledge gaps with operational stages of the development of
      NAS from a project designer perspective. We start by highlighting the key role of
      the insurance industry in incentivizing and assessing disaster and slow onset
      resilience enhancement strategies. In parallel we place the public sector as
      potential kick-starters in DRE initiatives through the existing initiatives and
      constraints of infrastructure procurement. Under this perspective the paper
      explores the required alignment of Integrated Water resources planning and Public
      investment systems. Ultimately this will provide the possibility for both
      planners and investors to design no regret NBS and mixed Grey-Green
      infrastructures systems. As resources and constraints are widely different
      between infrastructure development contexts, the framework does not provide
      explicit methodological choices but presents current limits of knowledge and know
      how. In conclusion the paper underlines the potential of NAS to ease the
      infrastructure gap in water globally by stressing the advantages of investment in
      the protection, enhancement and restoration of natural capital as an effective
      climate change adaptation investment.

PMID- 28763732
TI  - Exposure to air pollution and noise from road traffic and risk of congenital
      anomalies in the Danish National Birth Cohort.
AB  - BACKGROUND: Ambient air pollution has been associated with certain congenital
      anomalies, but few studies rely on assessment of fine-scale variation in air
      quality and associations with noise from road traffic are unexplored. METHODS:
      Among 84,218 liveborn singletons (1997-2002) from the Danish National Birth
      Cohort with complete covariate data and residential address history from
      conception until birth, we identified major congenital anomalies in 4018
      children. Nitrogen dioxide (NO2) and noise from road traffic (Lden) burden during
      fetal life was modeled. Outcome and covariate data were derived from registries,
      hospital records and questionnaires. Odds ratios (ORs) for eleven major anomaly
      groups associated with road traffic pollution during first trimester were
      estimated using logistic regression with generalized estimating equation (GEE)
      approach. RESULTS: Most of the associations tested did not suggest increased
      risks. A 10-ug/m3 increase in NO2 exposure during first trimester was associated
      with an adjusted ORs of 1.22 (95% confidence interval: 0.98-1.52) for ear, face
      and neck anomalies; 1.14 0.98-1.33) for urinary anomalies. A 10-dB increase in
      road traffic noise was also associated with these subgroups of anomalies as well
      as with an increased OR for orofacial cleft anomalies (1.17, 0.94-1.47). Inverse
      associations for several both air pollution and noise were observed for atrial
      septal defects (0.85, 0.68-1.04 and 0.81, 0.65-0.99, respectively). CONCLUSIONS:
      Residential road traffic exposure to noise or air pollution during pregnancy did
      not seem to pose a risk for development of congenital anomalies.

PMID- 28763730
TI  - Fine particulate matter and cardiovascular disease: Comparison of assessment
      methods for long-term exposure.
AB  - BACKGROUND: Adverse cardiovascular events have been linked with PM2.5 exposure
      obtained primarily from air quality monitors, which rarely co-locate with
      participant residences. Modeled PM2.5 predictions at finer resolution may more
      accurately predict residential exposure; however few studies have compared
      results across different exposure assessment methods. METHODS: We utilized a
      cohort of 5679 patients who had undergone a cardiac catheterization between 2002
      2009 and resided in NC. Exposure to PM2.5 for the year prior to catheterization
      was estimated using data from air quality monitors (AQS), Community Multiscale
      Air Quality (CMAQ) fused models at the census tract and 12km spatial resolutions,
      and satellite-based models at 10km and 1km resolutions. Case status was either a
      coronary artery disease (CAD) index >23 or a recent myocardial infarction (MI).
      Logistic regression was used to model odds of having CAD or an MI with each 1
      unit (MUg/m3) increase in PM2.5, adjusting for sex, race, smoking status,
      socioeconomic status, and urban/rural status. RESULTS: We found that the elevated
      odds for CAD>23 and MI were nearly equivalent for all exposure assessment
      methods. One difference was that data from AQS and the census tract CMAQ showed a
      rural/urban difference in relative risk, which was not apparent with the
      satellite or 12km-CMAQ models. CONCLUSIONS: Long-term air pollution exposure was
      associated with coronary artery disease for both modeled and monitored data.

PMID- 28763733
TI  - Finding the sweet spot: Developing, implementing and evaluating a burn out and
      compassion fatigue intervention for third year medical trainees.
AB  - Medical trainees are at high risk for developing burnout. Introducing trainees to
      the risks of burnout and supporting identification and proactive responses to
      their 'warning' signs of compassion fatigue (CF) is critical in building
      resiliency. The authors developed and evaluated a burnout and CF program for
      third year trainees at a Canadian Medical School. Of 165 medical trainees who
      participated in the burnout and CF program, 59 (36%) provided evaluation and
      feedback of the program and its impact throughout their year. Participation
      included self-utilization of a validated CF and burnout tool (ProQOL) across
      three time-points, workshop feedback, and focus group participation. Results
      highlighted the importance of 1) Recognizing Individual Signs & Symptoms of
      Stress, CF and Burnout; 2) Normalizing Stress, CF and Burnout for Students and
      Physicians; 3) Learning to Manage One's Own Stress. A decrease in compassion
      satisfaction and increase in burnout between beginning and end of third year were
      found. Further outcomes highlighted the importance of learning, living and
      surviving CF and burnout in clerkship. Emergent theory reveals the important
      responsibility educators have to integrate CF and burnout programs into 'the
      sweet spot' that third year offers, as trainees shift from theoretical to
      experiential practice as future clinicians.

PMID- 28763734
TI  - Interfacial microstructure and mechanical properties of Cf/AZ91D composites with
      TiO2 and PyC fiber coatings.
AB  - In spite of the effectiveness of the fiber coatings on interface modification of
      carbon fiber reinforced magnesium matrix composites, the cost and exclusive
      equipment for the coatings preparation are usually ignored during research work.
      In this paper, pyrolytic carbon (PyC) and TiO2 were coated on carbon fiber
      surface to study the effects of fiber coatings on interfacial microstructure and
      mechanical properties of carbon fiber reinforced AZ91D composites (Cf/AZ91D
      composites). It was indicated that both the two coatings could modify the
      interface and improve the mechanical properties of the composites. The ultimate
      tensile strength of the TiO2-Cf/AZ91D and the PyC-Cf/AZ91D composite were 333MPa
      and 400MPa, which were improved by 41.7% and 70.2% respectively, compared with
      the untreated-Cf/AZ91D composite. The microstructure observation revealed that
      the strengthening of the composites relied on fiber integrity and moderate
      interfacial bonding. MgO nano-particles were generated at the interface due to
      the reaction of TiO2 with Mg in the TiO2-Cf/AZ91D composite. The volume expansion
      resulting from the reaction let to disordered intergranular films and crystal
      defects at the interface. The fibers were protected and the interfacial reaction
      was restrained by PyC coating in the PyC-Cf/AZ91D composite. The principle to
      select the coating of fiber was proposed by comparing the effectiveness and cost
      of the coatings.

PMID- 28763735
TI  - A new scanning mode to improve scanning ion conductance microscopy imaging rate
      with pipette predicted movement.
AB  - Scanning ion conductance microscopy (SICM) is a non-contact surface topography
      measurement technique that has been increasingly used for soft surfaces such as
      living biological samples. An approach-retract scanning (ARS) mode is widely used
      to avoid collision between the SICM probe (i.e., pipette) and an abrupt increase
      in sample profile. However, the redundant pipette trajectory in the ARS mode
      lengthens the scan time, thus reducing SICM efficiency and time resolution. To
      avoid this problem, a new scanning mode is discussed that adds horizontal
      movement at each measurement point to predict the upcoming sample topography via
      variation in ion current. The pipette then retracts in response to raised
      topography, while it raster scans flat or downhill topography. The feasibility
      was verified by finite element analysis and experimental tests on three kinds of
      soft samples: polydimethylsiloxane, mice cardiac fibroblasts, and breast cancer
      cells. The pixel detection frequency during imaging and the mean square error of
      the sample topography were compared for the two modes. The new scanning mode
      enhances the SICM imaging rate without loss of imaging quality or scanning
      stability, while it increases efficiency and time resolution. It thus has an
      improved performance for characterizing biological samples.

PMID- 28763736
TI  - Schizophrenia dissection by five anxiety and depressive subtype comorbidities:
      Clinical implications and evolutionary perspective.
AB  - Twenty patients with DSM5 schizophrenia were comprehensively and formally
      assessed by an experienced psychiatrist. All subjects were assessed for: positive
      and negative psychotic symptoms; social anxiety; panic anxiety; obsessive
      compulsive disorder, atypical depression; major depression; suicide risk; and
      global assessment of functioning. Different profiles of clinical presentation and
      symptom evolution emerged for patients with schizophrenia who had co-morbid
      depression (15%), OCD (15%), panic or limited symptom attacks (55%) and social
      anxiety (5%). At least eighty percent of the sample had one or more of these co
      morbidities. Summing up, the data support our previous finding that panic is
      highly prevalent in Schizophrenia with Auditory Hallucinations (>73% here, versus
      100% before), and panic was paroxysmally concurrent with voice onset. Moreover,
      characteristic clinical findings may help point clinicians to five specific co
      morbidity psychosis subtypes. Moreover, co-morbidity dissection of psychotic
      diagnoses recalls and parallels the historical psychopharmacologic dissection of
      non-psychotic anxiety and depressive subtypes diagnoses. Larger studies should
      further test and explore these preliminary findings.

PMID- 28763737
TI  - Attentional avoidance increases voice hearing in an analogue task in people with
      psychosis: An experimental study.
AB  - Cognitive models of psychosis suggest that unhelpful ways of responding to
      experiences can maintain such experiences and the associated distress. The
      response styles of attentional avoidance and attentional focusing were
      manipulated in an analogue voice-hearing task. Predictions were that both would
      increase detection of words in response to an ambiguous audio-recording but that
      attentional avoidance would lead to a greater increase than focusing. We also
      predicted that there would be a greater increase in anxiety and distress in the
      avoidance group. Predictions were tested in a sample of 44 participants with a
      diagnosis of schizophrenia. Participants were randomly assigned to either
      attentional avoidance or focusing while listening to an ambiguous auditory task.
      Number of words identified and anxiety and distress were recorded. As predicted,
      there was an increase in the number of words identified in both groups; however,
      this increase was greater in the avoidance group. The prediction that there would
      also be an increase in distress that would be greater in the avoidance group was
      not supported. It is possible that emotional reactions relate more closely to
      appraisals of the voice. The results suggest that avoidance of experiences is
      particularly counterproductive and can result in greater detection of
      experiences.

PMID- 28763738
TI  - Cost-effectiveness of simulation-based team training in obstetric emergencies
      (TOSTI study).
AB  - OBJECTIVE: Team training is frequently applied in obstetrics. We aimed to
      evaluate the cost-effectiveness of obstetric multi-professional team training in
      a medical simulation centre. STUDY DESIGN: We performed a model-based cost
      effectiveness analysis to evaluate four strategies for obstetric team training
      from a hospital perspective (no training, training without on-site repetition and
      training with 6 month or 3-6-9 month repetition). Data were retrieved from the
      TOSTI study, a randomised controlled trial evaluating team training in a medical
      simulation centre. We calculated the incremental cost-effectiveness ratio (ICER),
      which represent the costs to prevent the adverse outcome, here (1) the composite
      outcome of obstetric complications and (2) specifically neonatal trauma due to
      shoulder dystocia. RESULTS: Mean costs of a one-day multi-professional team
      training in a medical simulation centre were ?25,546 to train all personnel of
      one hospital. A single training in a medical simulation centre was less effective
      and more costly compared to strategies that included repetition training.
      Compared to no training, the ICERs to prevent a composite outcome of obstetric
      complications were ?3432 for a single repetition training course on-site six
      months after the initial training and ?5115 for a three monthly repetition
      training course on-site after the initial training during one year. When we
      considered neonatal trauma due to shoulder dystocia, a three monthly repetition
      training course on-site after the initial training had an ICER of ?22,878.
      CONCLUSION: Multi-professional team training in a medical simulation centre is
      cost-effective in a scenario where repetition training sessions are performed on
      site.

PMID- 28763739
TI  - Risk of malignancy on suspicion of polyps in menopausal women.
AB  - : Improved performances in gynaecological ultrasonography have enabled an
      increasing number of often asymptomatic endometrial polyps to be detected. Most
      of these polyps are removed surgically, as a precautionary measure, so as not to
      miss a case of endometrial cancer. Nonetheless, this management strategy is based
      solely on the sonographer's judgement and a number of these operations, which are
      probably of no benefit, could be avoided. In order to do so, risk factors for
      malignancy need to be identified. OBJECTIVE: Estimate the prevalence of lesions
      in menopausal patients with a pre-operative diagnosis of endometrial polyp.
      Establish risk factors for malignancy. STUDY DESIGN: This is a single-centre
      retrospective study. Enrolment criteria were menopausal patients aged over 45 who
      had undergone hysteroscopic resection of a polyp. Pre-op diagnosis was made
      either by ultrasonography or diagnostic hysteroscopy. Malignant lesions included
      cancers and atypical hyperplasia. Benign lesions consisted of simple polyps, non
      atypical simple hyperplasia and non-atypical complex hyperplasia. Risk factors
      studied were existing abnormal uterine bleeding, endometrial thickness, personal
      or first-degree family history of gynaecological cancer (breast, cervix,
      endometrium, ovary) and age on diagnosis. RESULTS: 631 patients were enrolled of
      whom 30 presented a malignant disorder (4.75%); 579 patients (91.76%) presented a
      simple polyp, 11 a non-atypical simple hyperplasia (1.74%) and 11 a non-atypical
      complex hyperplasia (1.74%). On univariate analysis age alone proved to be
      statistically significant (OR 1.05; 95%CI=[1.02-1.09] p<0.01), with a threshold
      of 59 years of age on the ROC curve. On multivariate analysis, factors predictive
      of a malignant lesion were age (OR=1.06; 95%CI [1.02-1.10]), existence of AUB
      (OR=2.4; 95% CI [1.07-5.42]) and family history (OR=2.88; 95%CI [1.08-7.67]).
      Neither the univariate nor multivariate model was able to demonstrate a
      statistically significant relationship with respect to endometrial thickness. The
      risk of malignancy was 12.3% in patients aged over 59 presenting AUB. For all
      other subgroups, the risk varied between 2.31 and 3.78%. CONCLUSION: The risk of
      a malignant lesion appears to be high (12%) in menopausal patients aged over 59
      presenting an endometrial polyp detected when there is pre-existing AUB. In this
      situation, hysteroscopic resection of endometrial polyps should therefore be
      routinely proposed. For other patients, the risk of a malignant lesion is low but
      not insignificant, standing at about 3%. Each patient record should therefore be
      discussed on an individual case basis, taking into consideration the patient's
      pre-existing conditions, after providing clear and appropriate information.

PMID- 28763740
TI  - What European gynaecologists need to master: Consensus on medical expertise
      outcomes of pan-European postgraduate training in obstetrics & gynaecology.
AB  - OBJECTIVE: European harmonisation of training standards in postgraduate medical
      education in Obstetrics and Gynaecology is needed because of the increasing
      mobility of medical specialists. Harmonisation of training will provide quality
      assurance of training and promote high quality care throughout Europe. Pan
      European training standards should describe medical expertise outcomes that are
      required from the European gynaecologist. This paper reports on consensus
      development on the medical expertise outcomes of pan-European training in
      Obstetrics and Gynaecology. STUDY DESIGN: A Delphi procedure was performed
      amongst European gynaecologists and trainees in Obstetrics & Gynaecology, to
      develop consensus on outcomes of training. The consensus procedure consisted of
      two questionnaire rounds, followed by a consensus meeting. To ensure
      reasonability and feasibility for implementation of the training standards in
      Europe, implications of the outcomes were considered in a working group
      thereafter. We invited 142 gynaecologists and trainees in Obstetrics &
      Gynaecology for participation representing a wide range of European countries.
      They were selected through the European Board & College of Obstetrics and
      Gynaecology and the European Network of Trainees in Obstetrics & Gynaecology.
      RESULTS: Sixty people participated in round 1 and 2 of the consensus procedure,
      38 (63.3%) of whom were gynaecologists and 22 (36.7%) were trainees in Obstetrics
      & Gynaecology. Twenty-eight European countries were represented in this response.
      Round 3 of the consensus procedure was performed in a consensus meeting with six
      experts. Implications of the training outcomes were discussed in a working group
      meeting, to ensure reasonability and feasibility of the material for
      implementation in Europe. The entire consensus procedure resulted in a core
      content of training standards of 188 outcomes, categorised in ten topics.
      CONCLUSION: European consensus was developed regarding the medical expertise
      outcomes of pan-European training in Obstetrics and Gynaecology. The outcomes
      will be described in core trainings standards, aimed at harmonising training in
      Obstetrics and Gynaecology in Europe to promote high quality care.

PMID- 28763741
TI  - Expression stability and selection of optimal reference genes for gene expression
      normalization in early life stage rainbow trout exposed to cadmium and copper.
AB  - Gene expression analysis represents a powerful approach to characterize the
      specific mechanisms by which contaminants interact with organisms. One of the key
      considerations when conducting gene expression analyses using quantitative real
      time reverse transcription-polymerase chain reaction (qPCR) is the selection of
      appropriate reference genes, which is often overlooked. Specifically, to reach
      meaningful conclusions when using relative quantification approaches, expression
      levels of reference genes must be highly stable and cannot vary as a function of
      experimental conditions. However, to date, information on the stability of
      commonly used reference genes across developmental stages, tissues and after
      exposure to contaminants such as metals is lacking for many vertebrate species
      including teleost fish. Therefore, in this study, we assessed the stability of
      expression of 8 reference gene candidates in the gills and skin of three
      different early life-stages of rainbow trout after acute exposure (24h) to two
      metals, cadmium (Cd) and copper (Cu) using qPCR. Candidate housekeeping genes
      were: beta actin (b-actin), DNA directed RNA polymerase II subunit I (DRP2),
      elongation factor-1 alpha (EF1a), glyceraldehyde 3-phosphate dehydrogenase
      (GAPDH), glucose-6-phosphate dehydrogenase (G6PD), hypoxanthine
      phosphoribosyltransferase (HPRT), ribosomal protein L8 (RPL8), and 18S ribosomal
      RNA (18S). Four algorithms, geNorm, NormFinder, BestKeeper, and the comparative
      DeltaCt method were employed to systematically evaluate the expression stability
      of these candidate genes under control and exposed conditions as well as across
      three different life-stages. Finally, stability of genes was ranked by taking
      geometric means of the ranks established by the different methods. Stability of
      reference genes was ranked in the following order (from lower to higher
      stability): HPRT<GAPDH<EF1a<G6PD<RPL8<DRP2<b-actin in gills of fish exposed to
      Cd; b-actin<GAPDH<G6PD<DRP2<RPL8<HPRT<EF1a in gills of fish exposed to Cu;
      RPL8<HPRT<GAPDH<G6PD<EF1a<DRP2<b-actin in the skin of fish exposed to Cd; and
      EF1a<GAPDH<RPL8<HPRT<G6PD<b-actin<DRP2 in the skin of fish exposed to Cu. The
      results demonstrated that the stability of reference genes depended on the metal,
      life-stage and/or organ in question. Thus, attention should be paid to these
      factors before selection of reference gene for relative quantification of the
      gene expressions.

PMID- 28763742
TI  - The increased toxicity of UV-degraded nitroguanidine and IMX-101 to zebrafish
      larvae: Evidence implicating oxidative stress.
AB  - Insensitive munitions (IMs) improve soldier safety by decreasing sympathetic
      detonation during training and use in theatre. IMs are being increasingly
      deployed, although the environmental effects of IM constituents such as
      nitroguanidine (NQ) and IM mixture formulations such as IMX-101 remain largely
      unknown. In the present study, we investigated the acute (96h) toxicity of NQ and
      IMX-101 to zebrafish larvae (21d post-fertilization), both in the parent
      materials and after the materials had been irradiated with environmentally
      relevant levels of ultraviolet (UV) light. The UV-treatment increased the
      toxicity of NQ by 17-fold (LC50 decreased from 1323mg/L to 77.2mg/L). Similarly,
      UV-treatment increased the toxicity of IMX-101 by nearly two fold (LC50 decreased
      from 131.3 to 67.6mg/L). To gain insight into the cause(s) of the observed UV
      enhanced toxicity of the IMs, comparative molecular responses to parent and UV
      treated IMs were assessed using microarray-based global transcript expression
      assays. Both gene set enrichment analysis (GSEA) and differential transcript
      expression analysis coupled with pathway and annotation cluster enrichment were
      conducted to provide functional interpretations of expression results and
      hypothetical modes of toxicity. The parent NQ exposure caused significant
      enrichment of functions related to immune responses and proteasome-mediated
      protein metabolism occurring primarily at low, sublethal exposure levels (5.5 and
      45.6mg/L). Enriched functions in the IMX-101 exposure were indicative of
      increased xenobiotic metabolism, oxidative stress mitigation, protein
      degradation, and anti-inflammatory responses, each of which displayed
      predominantly positive concentration-response relationships. UV-treated NQ had a
      fundamentally different transcriptomic expression profile relative to parent NQ
      causing positive concentration-response relationships for genes involved in
      oxidative-stress mitigation pathways and inhibited expression of multiple
      cadherins that facilitate zebrafish neurological and retinal development.
      Transcriptomic profiles were similar between UV-treated versus parent IMX-101
      exposures. However, more significant and diverse enrichment as well as greater
      magnitudes of differential expression for oxidative stress responses were
      observed in UV-treated IMX-101 exposures. Further, transcriptomics indicated
      potential for cytokine signaling suppression providing potential connections
      between oxidative stress and anti-inflammatory responses. Given the overall
      results, we hypothesize that the increased toxicity of UV-irradiated NQ and the
      IMX-101 mixture result from breakdown products with elevated potential to elicit
      oxidative stress.

PMID- 28763743
TI  - Synergistic effects of some essential oils against fungal spoilage on pear fruit.
AB  - The development of natural protective agents as alternatives to chemical
      fungicides is currently in the spotlight. In the present investigation, chemical
      composition and antifungal activities of thyme, cinnamon, rosemary and marjoram
      essential oils (EO), as well as synergism of their possible double and triple
      combinations were investigated. The compositions of the oils were determined by
      GC/MS. For determination of antifungal activity against Penicillium expansum and
      Botrytis cinerea, a broth microdilution method was used. The possible
      interactions of some essential oil combinations were performed by the two and
      three-dimensional checkerboard assay and isobologram construction. An in vivo
      antifungal assay was performed by artificial wounding of pear fruits. The maximum
      antifungal activity was demonstrated by thyme and cinnamon oils which displayed
      lower MIC values whereas rosemary and marjoram oils with MIC range between 2500
      and 10,000MUg/mL exhibited weak antifungal activities against tested fungi. In
      synergy testing, some double combinations (thyme/cinnamon, thyme/rosemary,
      cinnamon/rosemary) were found to be synergistic (FICi<=0.5). The triple
      combination of thyme, cinnamon and rosemary was synergistic for B. cinerea and P.
      expansum (FICi values of 0.5 and 0.375, respectively); while combination of
      cinnamon, marjoram and thyme exhibited additive and synergistic effect against P.
      expansum (FIC=0.625) and B. cinerea (FIC=0.375) respectively. The usage of a
      mathematical Gompertz model in relation to fungal kinetics, showed that the model
      could be used to predict growth curves (R2=0.993+/-0.05). For B. cinerea,
      Gompertz parameters for double and triple combination treatments showed
      significant increase in lag phase (1.92 and 2.92days, respectively) compared to
      single treatments. Increase lag time up to 2.82days (P<0.05) also observed in P.
      expansum treated by triple combination of EOs. Base on the results, the lowest
      maximum growth rate (0.37mm/day) was observed in B. cinerea treated by triple
      combination of thyme, cinnamon and rosemary. The in vivo test also demonstrated
      considerable inhibitory effects of EO combination treatments. Average lesion
      diameter of pears treated with triple combination of cinnamon/rosemary/thyme (78,
      1250, 39MUg/mL) was 6mm and 8mm against B. cinerea and P. expansum respectively,
      in 10days at 25 degrees C. Results also showed that double combination of
      thyme/cinnamon (78, 156MUg/mL) has more inhibitory effect than single EO
      treatments.

PMID- 28763744
TI  - Genetic polymorphisms and valproic acid plasma concentration in children with
      epilepsy on valproic acid monotherapy.
AB  - PURPOSE: The aim of the study is to evaluate the association between genetic
      polymorphisms and valproic acid (VPA) concentration to dose ratio in children
      with epilepsy on VPA monotherapy. METHODS: A total of 137 children, aged 3.5-18
      years, (89 males and 48 females) with epilepsy on sustained-release VPA
      monotherapy were enrolled. Trough plasma concentrations of VPA at steady-state
      were measured using an AXSYM automatic immunity analyzer. The values were divided
      by body weight and total daily dose to calculate concentration to dose ratio of
      VPA (CDRV). Forty-eight single nucleotide polymorphisms involved in the
      pharmacokinetics of VPA were identified by MassARRAY system. The logarithmic
      transformed CDRV (lnCDRV) was normally distributed, and PLINK software was used
      to evaluate the association between genetic polymorphisms and lnCDRV using linear
      regression adjusted for gender and seizure type. RESULTS: rs28898617
      (UGT1A3/4/5/6/7/8/9/10, BETA=0.32, P=0.0089) was significantly associated with
      higher lnCDRV. No other associations were found. CONCLUSIONS: In pediatric
      patients taking VPA monotherapy, rs28898617 was associated with a higher
      normalized VPA plasma concentration. Further studies are warranted to confirm the
      results.

PMID- 28763745
TI  - Carbenoxolone reduces cyclic nucleotides level, destabilizes maturation promoting
      factor and induces meiotic exit from diplotene arrest in rat cumulus oocytes
      complexes cultured in vitro.
AB  - BACKGROUND: Disruption of gap junction and transfer of cyclic nucleotides to the
      oocyte lead to meiotic exit from diplotene arrest (EDA) in mammals. In the
      present study, we examined whether a gap junction blocker, carbenoxolone (CBX)
      could induce EDA by reducing cyclic nucleotides level and destabilizing
      maturation promoting factor (MPF) in rat oocytes cultured in vitro. METHODS:
      Diplotene-arrested cumulus oocyte complexes (COCs) were collected from ovary of
      immature female rats after 20 IU pregnant mare's serum gonadotropins (PMSG) for
      48h. These diplotene-arrested COCs were incubated with various concentration of
      CBX for 3h in vitro. The morphological changes, meiotic status of oocyte,
      inducible nitric oxide synthase (iNOS), total nitric oxide (NO), adenosine 3',5'
      cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), cell
      division cycle 25B (Cdc25B), changes in specific phosphorylation status of cyclin
      dependent kinase 1 (Cdk1) and cyclin B1 levels were analyzed. RESULTS: CBX
      induced EDA in a concentration-dependent manner. The iNOS expression, total NO
      and cyclic nucleotides level were significantly decreased. The reduced cyclic
      nucleotides level resulted in the decrease of Cdc25B expression level. The
      decreased Cdc25B was associated with the increased Thr14/Tyr15 phosphorylated
      Cdk1 level. However, Thr161 phosphorylated Cdk1 as well as cyclin B1 levels were
      significantly reduced leading to MPF destabilization. The destabilized MPF
      finally induced EDA in rat COCs cultured in vitro. CONCLUSIONS: Our results
      suggest that CBX blocked gap junctions interrupted the transfer of cyclic
      nucleotides to the oocyte. Reduction of cyclic nucleotides level destabilized MPF
      and induced EDA in vitro. Thus, CBX could be used to induce meiotic maturation
      under in vitro culture conditions during assisted reproductive technology (ART)
      programs.

PMID- 28763746
TI  - Rhein ameliorates adenomyosis by inhibiting NF-kappaB and beta-Catenin signaling
      pathway.
AB  - In the present study, we examined the effects of rhein on pituitary gland
      implantation-induced adenomyosis, an animal model which mimics human adenomyosis.
      Oral administration of rhein dose-dependently attenuated hyperplastic and
      hypertrophic myometrium and improved adenomyosis. The activation of NF-kappaB and
      beta-catenin signaling pathway was observed in the ectopic endometria. While,
      rhein dose dependently inhibited the expressions of p-p65, p-AKT and actived
      Rac1. As Rac1 activation controlled nuclear localization of beta-catenin during
      canonical Wnt signaling, we found that the degradation complex of beta-catenin
      was improved by rhein. In addition, beta-catenin nuclear translocation and its
      downstream genes were markedly suppressed by different doses of rhein. At the
      same time, decreased activation of epithelial-mesenchymal transition (EMT)
      associated proteins including Snail and ZEB1 was detected in rhein-treated mice,
      indicating that the activation of Wnt signaling pathway was suppressed by rhein.
      The in vitro study verified a negative regulation of rhein on beta-catenin in
      stromal cells. Stimulation of IL-1beta significantly increased the nuclear
      translocation of beta-catenin and improved its target genes expressions. While,
      rhein remarkably abolished the enhancement in a dose dependent manner. Taken
      together, our results demonstrated the ability of rhein to inhibit Wnt/beta
      catenin activation and its potential use in the treatment of adenomyosis and
      other abnormal activation of beta-catenin -associated diseases.

PMID- 28763747
TI  - Long intergenic noncoding RNA 00305 sponges miR-136 to regulate the hypoxia
      induced apoptosis of vascular endothelial cells.
AB  - BACKGROUND: Apoptosis in vascular endothelial cells (VECs) are closely correlated
      to multiple endotheliocyte-related cardiovascular diseases, for example
      atherosclerosis. Long non-coding RNAs (lncRNAs) have been testified to play
      important role in regulation of VECs. The purpose of this study is to investigate
      the potential regulation of lncRNA long intergenic noncoding RNA 00305
      (LINC00305) on hypoxia induced VECs. METHODS: Human umbilical vein endothelial
      cells (HUVECs) were respectively induced with normoxia or hypoxia (1%).
      Expression levels of lncRNA and miRNA were detected using RT-PCR. Proliferation
      ability was tested by CCK-8 assay. Apoptosis assay were performed using flow
      cytometry and TUNEL staining. Target miRNAs prediction was performed using
      bioinformatics analysis. RESULTS: LINC00305 expression was significantly up
      regulated in hypoxia induce HUVECs. Gain- and loss-of-function experiments showed
      that LINC00305 enhanced expression suppressed the proliferation and enhanced the
      apoptosis of HUVECs, while LINC00305 lower-expression exerted the opposite
      effect. Bioinformatics analysis revealed that miR-136 targeted LINC00305 art 3'
      UTR. Moreover, rescue experiment confirmed the reversing function of miR-136 to
      LINC00305 on HUVECs proliferation and apoptosis. CONCLUSION: Our study revealed
      the apoptosis-promoting role of LINC00305 in hypoxia-induced HUVECs via acting as
      miR-136 sponge, suggesting the vital function of lncRNAs on VECs apoptosis.

PMID- 28763749
TI  - Protective effects of ethanolic peel and pulp extracts of Citrus macroptera fruit
      against isoproterenol-induced myocardial infarction in rats.
AB  - Increases in the incidence of cardiovascular disease (CVD) have aroused strong
      interest in identifying antioxidants from natural sources for use in preventive
      medicine. Citrus macroptera (C. macroptera), commonly known as "Satkara", is an
      important herbal and medicinal plant reputed for its antioxidant, nutritious and
      therapeutic uses. The aim of the present study was to investigate the cardio
      protective effects of ethanol extracts of C. macroptera peel and pulp against
      isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino
      Wistar rats (n=36) were pre-treated with peel and pulp extracts (500mg/kg) for
      45days. They received a challenge with ISO (85mg/kg) on the 44th and 45th days.
      Our findings indicated that subcutaneous injection of ISO induced severe
      myocardial injuries associated with oxidative stress, as confirmed by elevated
      lipid peroxidation (LPO) and decreased cellular reduced glutathione (GSH) and
      anti-peroxidative enzymes, including glutathione peroxidase, glutathione
      reductase and glutathione-S-transferase, compared with levels observed in control
      animals. Pre-treatment with C. macroptera peel and pulp extracts prior to ISO
      administration however, significantly improved many of the investigated
      biochemical parameters, i.e., cardiac troponin I, cardiac marker enzymes, lipid
      profile and oxidative stress markers. The fruit peel extract showed stronger
      cardio-protective effects than the pulp extract. The biochemical findings were
      further confirmed by histopathological examinations. Overall, the increased
      endogenous antioxidant enzyme activity against heightened oxidative stress in the
      myocardium is strongly suggestive of the cardio-protective potential of C.
      macroptera.

PMID- 28763748
TI  - The therapeutic effects of Yongdamsagan-tang on autoimmune hepatitis models.
AB  - Autoimmune hepatitis (AIH) is an immunity disorder that is the result of
      antibodies in the liver tissue of the patient that are attacked by activated
      immune cells due to an unknown cause. In this study, we aimed to investigate the
      anti-inflammatory effect of Yongdamsagan-tang (YST) extracts and confirm effects
      on autoimmune hepatitis models as the therapeutic agent using the YST extracted
      by various solvents. YST, a mixture of 11 herbal extracts, is known in
      traditional Korean medicine as a widely used treatment for inflammatory diseases.
      We proposed the AIH-condition in vitro model by the addition of recombinant IL
      17A and then observed several markers linked to AIH symptoms, including an
      increase of IL-6 expression, lipid accumulation, and fibrosis. In AIH-condition
      hepatic cell model, YST reduced IL-6 expression and lipid accumulation caused by
      treatment of IL-17 combination in hepatocyte cells. Also, YST blocked several
      activated fibrosis factors including transforming growth factor-beta (TGF-
      beta1), collagen type 1 (Col-alpha1(I)), and alpha-smooth muscle actin (alpha
      SMA) in liver stellate cells. Furthermore, pretreatment with YST protected
      hepatic damage and reduces histological injury by suppressing apoptosis mediator
      and inflammatory cytokines expression in concanavalin A (Con A)-induced
      autoimmune hepatitis mice model. The findings here improve our understanding of
      YST extracted by 80% ethanol, suggesting that YST can be used as a therapeutic
      treatment for AIH.

PMID- 28763750
TI  - New insights into the antioxidant and apoptotic potential of Glycyrrhiza glabra
      L. during hydrogen peroxide mediated oxidative stress: An in vitro and in silico
      evaluation.
AB  - Plant-derived substances (phytochemicals) are well recognized as sources of
      pharmacologically potent drugs in the treatment of several oxidative stress
      related disorders. Our study aims to evaluate the antioxidant and apoptotic
      effects of Glycyrrhiza glabra L. in both cell free and cell culture system. Plant
      fractions have been prepared with hexane, chloroform, ethyl acetate, methanol and
      water and their antioxidant properties are reviewed. Potent antioxidant activity
      has been well established in both in vitro and in silico studies which is
      believed to be responsible for the anticancerous nature of the plant. Results
      obtained indicate that methanol fraction of G. glabra L. exhibited maximum
      scavenging activity against DPPH and nitric oxide free radicals comparable to
      standard antioxidant L-AA. Administration of methanol fraction also considerably
      reduced the malondialdehyde produced due to lipid peroxidation in mammalian liver
      tissues. Moreover, the levels of antioxidant enzymes SOD, CAT, GST, GPx and GR in
      the oxidative stress induced tissues were refurbished significantly after
      treatment with plant's methanol fraction. Moreover, methanol fraction was found
      to be nontoxic to normal human cell line whereas it inhibited cancer cells HeLa
      and HepG2 considerably. Apoptosis was established by DAPI fluorescent staining
      and western blot analysis of pro apoptotic protein caspase-8, caspase-3 and anti
      apoptotic protein Bcl-2.There is an up regulation in the levels of pro apoptotic
      caspase-8 and caspase-3 and down regulation of anti-apoptotic Bcl-2. Furthermore,
      GC-MS analysis of the methanol fraction revealed the presence of many compounds.
      In silico experiments using Autodock 4.2 tools showed strong affinity of plant
      compounds towards antioxidant enzymes (proteins) thus validating with the
      conclusions of antioxidant enzyme assays and establishing a role in cancer
      pathogenesis.

PMID- 28763751
TI  - Berberine ameliorates methotrexate-induced liver injury by activating Nrf2/HO-1
      pathway and PPARgamma, and suppressing oxidative stress and apoptosis in rats.
AB  - Berberine (BBR) is a natural isoquinoline alkaloid with very impressive health
      benefits. It is one of the most effective natural supplements available; however,
      its ameliorative mechanism against methotrexate (MTX)-induced liver injury is not
      well defined. This study investigated the protective effect of BBR against MTX
      hepatotoxicity, focusing on its ability to attenuate oxidative stress and
      apoptosis and to activate nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme
      oxygenase-1 (HO-1) signaling and peroxisome proliferator activated receptor gamma
      (PPARgamma). Rats received BBR (25 and 50mg/kg) orally for 7days before MTX
      injection. Other groups received MTX followed by BBR (25 and 50mg/kg) orally for
      7 days. MTX-induced rats showed significant body weight loss, increased serum
      liver function marker enzymes, bilirubin and tumor necrosis factor alpha (TNF
      alpha). Liver lipid peroxidation, nitric oxide (NO) and caspase-3 were
      significantly increased following MTX administration. BBR supplemented either
      before or after MTX significantly ameliorated body weight, liver function
      markers, TNF-alpha, lipid peroxidation, NO and caspase-3. BBR increased serum
      albumin and liver antioxidant defenses in MTX-induced rats. Histological and
      immunohistochemical examination showed improved histological structure and
      decreased expression of Bax in liver of MTX-induced rats treated with BBR. In
      addition, BBR up-regulated Nrf2, HO-1 and PPARgamma expression in the liver of
      MTX-induced rats. In conclusion, BBR attenuated MTX-induced oxidative stress and
      apoptosis, possibly through up-regulating Nrf2/HO-1 pathway and PPARgamma.
      Therefore, BBR can protect against MTX-induced liver injury.

PMID- 28763752
TI  - Chemical characterization, toxicology and mechanism of gastric antiulcer action
      of essential oil from Gallesia integrifolia (Spreng.) Harms in the in vitro and
      in vivo experimental models.
AB  - Gallesia integrifolia is a Brazilian Amazon tree whose bark decoction is
      popularly used to treat peptic ulcer. The essential oil from the inner stem bark
      of G. integrifolia (EOGi) was chemically characterized by GC/MS. The in vitro
      cytotoxicity and genotoxicity were evaluated in CHO-K1 cells, while the in vivo
      oral acute toxicity was performed in mice. The gastroprotective effect of EOGi
      was assessed in acidified ethanol and piroxicam and ulcer healing on acetic acid 
      induced ulcer models in rodents. Anti-secretory, mucus, K+-ATP channels,
      prostaglandins (PGs), nitric oxide (NO), TNF-alpha, IL-1beta, IL-10, catalase
      (CAT) and myeloperoxidase (MPO) activities and in vitro Helicobacter pylori
      action by EOGi were evaluated. EOGi exhibited cytotoxic effects only at 72h and
      no acute toxicity. EOGi showed gastroprotective and ulcer healing effects. EOGi
      gastroprotection was attenuated by indomethacin pre-treatment. Gastric volume and
      total acidity were reduced, while gastric pH was elevated. EOGi increased mucus
      and NO productions and CAT activity, and inhibited MPO activity, TNF-alpha and IL
      1beta concentrations and augmented IL-10. EOGi was not active against H. pylori.
      These results indicated that EOGi is safe and exerts preventive and curative
      gastric ulcer effects by multitarget actions. Twenty compounds were identified
      and (-)-alpha-santalene was the main compound.

PMID- 28763753
TI  - The anti-proliferative and apoptotic effects of crocin on chemosensitive and
      chemoresistant cervical cancer cells.
AB  - Cervical cancer is the fourth cause of cancer-related mortality among females
      worldwide. Although current therapies reduce disease symptoms, resistance of
      tumor cells to chemotherapy agents after a while is a serious problem. Therefore,
      utilization of novel adjuvant agents to increase efficiency of chemotherapy is
      essential. In the last two decades, botanicals with effective anticancer
      activities have been studied. Among them, the anticancer properties of crocin
      have been more attended. In this study, the molecular mechanism of crocin action
      was investigated in sensitive human cervical cancer cell line (OV2008) in
      comparison with the resistant one (C13). A 3-(4,5-dimethylthiazol-2-yl)-2,5-
      diphenyltetrazolium bromide (MTT) assay showed that crocin inhibits proliferation
      of sensitive cells (OV2008) at a time- and dose-dependent manner at 48 and 72h.
      Also, this inhibitory effect has been shown on resistant cells (C13) at 72h.
      Hoechst staining and flow cytometry assay also confirmed these results and
      revealed that antiproliferative effect of crocin might be due to the induction of
      apoptosis. Moreover, the genetic mechanism of crocin-induced apoptosis was
      accomplished by studying the relative expressions of P53, Bax, Bcl2 and miR-365,
      an upstream regulator of the last two ones. Real-time PCR analysis indicated that
      1.5 and 3mg/ml crocin led to up-regulation of Bax and P53 and down-regulation of
      Bcl2 and miR-365 at all time intervals in both two cell lines. However, OV2008
      cell line was more sensitive to crocin, and alternation of gene expretion was
      more obvious in this cell line. In this regard, the present study demonstrated
      the anti-proliferative and apoptotic activities of crocin against both sensitive
      and resistant cervical cancer cells that may benefit cervical cancer treatment as
      an adjuvant agent to decrease chemoresistance and increase the efficiency of
      therapy.

PMID- 28763754
TI  - Effects of prostaglandin E2 on clonogenicity, proliferation and expression of
      pluripotent markers in human periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Based on our earlier work on the response of
      periodontal ligament (PDL) cells to mechanical stress by induction of
      cyclooxygenase expression and production of prostaglandin PGE2 that could
      regulate mineralization of PDL cells, it was hypothesized that PGE2 had potential
      effects on PDL stemness. In this study, we aimed to investigate clonogenicity,
      proliferation and expression of certain pluripotent markers, considered to be
      characteristics of PDL stemness, in response to treatment with exogenously-added
      PGE2. MATERIAL AND METHODS: Human PDL cells were cultured and treated with
      various doses of PGE2, and the aforementioned characteristics of PDL stemness
      were analyzed. RESULTS: The clonogenicity and proliferation were significantly
      enhanced by PGE2 at low concentrations (0.01, 0.1 and 1ng/ml; P<0.05), but only
      the proliferation was significantly diminished by PGE2 at a high concentration
      (100ng/ml; P<0.05). Expression of NANOG and OCT4 mRNA and protein was increased
      by PGE2 treatment at 0.1 and 1ng/ml. Consistently, expression of stage-specific
      embryonic antigen 4, a putative stem cell marker, was significantly augmented by
      PGE2 treatment at 1ng/ml (P<0.05). CONCLUSION: Our findings suggest that although
      a high dose of PGE2 (100ng/ml) inhibits proliferation of PDL cells, PGE2 at low
      doses appears to play a role in the maintenance of PDL stemness.

PMID- 28763755
TI  - Investigating quality of life and self-stigma in Hong Kong children with specific
      learning disabilities.
AB  - BACKGROUND: Children with specific learning disabilities (SpLD) are likely to
      develop self-stigma and have a poor quality of life (QoL) because of their poor
      academic performance. Although both self-stigma and poor QoL issues are likely to
      be found in low academic achievers without SpLD, children with SpLD have worse
      situation because their diagnosis of SpLD suggests that their learning struggles
      are biological and permanent. Specifically, students' perception of own
      capabilities may be affected more by the diagnosis of SpLD than their own actual
      performance. AIMS: We examined the self-stigma and QoL of children with SpLD in
      Hong Kong, a region with an academics-focused culture. METHODS AND PROCEDURES:
      Children with SpLD (n=49,Mage+/-SD=9.55+/-1.21; SpLD group) and typically
      developing children (n=32,Mage+/-SD=9.81+/-1.40; TD group) completed a Kid-KINDL
      to measure QoL and a Modified Self-Stigma Scale to measure self-stigma. All
      parents completed a parallel Kid-KINDL to measure QoL of their children. OUTCOMES
      AND RESULTS: Compared with the TD group, the SpLD group had a higher level of
      self-stigma (p=0.027) and lower QoL (child-reported Kid-KINDL: p=0.001; parent
      reported Kid-KINDL: p<0.001). CONCLUSIONS AND IMPLICATIONS: In the academics
      focused environment in Hong Kong, SpLD was associated with impaired QoL and
      higher self-stigma. Treatments targeting the learning process of children with
      SpLD may be designed to overcome self-stigma and to improve QoL. In addition, the
      program may involve parents of the children with SpLD or other people (e.g., the
      peer of the children with SpLD) for improving their understanding and perceptions
      of SpLD.

PMID- 28763756
TI  - Activity, biomass and composition of microbial communities and their degradation
      pathways in exposed propazine soil.
AB  - Propazine is a s-triazine herbicide widely used for controlling weeds for crop
      production. Its persistence and contamination in environment nagatively affect
      crop growth and food safety. Elimination of propazine residues in the environment
      is critical for safe crop production. This study identified a microbial community
      able to degrade propazine in a farmland soil. About 94% of the applied propazine
      was degraded within 11 days of incubation when soil was treated with 10mgkg-1
      propazine as the initial concentration. The process was accompanied by increased
      microbial biomass and activities of soil enzymes. Denaturing gradient gel
      electrophoresis (DGGE) revealed multiple bacterial strains in the community as
      well as dynamic change of the composition of microbial community with a reduced
      microbial diversity (H' from 3.325 to 2.78). Tracking the transcript level of
      degradative genes AtzB, AtzC and TrzN showed that these genes were induced by
      propazine and played important roles in the degradation process. The activities
      of catalase, dehydrogenase and phenol oxidase were stimulated by propazine
      exposure. Five degradation products (hydroxyl-, methylated-, dimeric-propazine,
      ammeline and ammelide) were characterized by UPLC-MS2, revealing a biodegradation
      of propazine in soil. Several novel methylated and dimeric products of propazine
      were characterized in thepropazine-exposed soil. These data help understand the
      pathway, detailed mechanism and efficiency of propazine biodegradation in soil
      under realistic field condition.

PMID- 28763757
TI  - Short-term influence of Cu, Zn, Ni and Cd excess on metabolism, ultrastructure
      and distribution of elements in lichen Xanthoria parietina (L.) Th. Fr.
AB  - Lichens are symbiotic organisms that are very sensitive to heavy metal pollution.
      However, there is little evidence of how heavy metal pollution affects the
      physiological status, ultrastructural changes and distribution of elements in the
      layers of lichen thalli. For this purpose we simulated metal pollution to lichens
      and studied its impact on Xanthoria parietina. Thalli were treated with the heavy
      metals Cu, Zn, Ni, Cd in the form of sulfates at concentrations of 100uM and
      500uM during 24, 48 and 72h. Untreated lichens served as controls. We assessed
      the status of physiological parameters (fluorescence and integrity of chlorophyll
      a, content of soluble proteins and ergosterol), ultrastructural changes,
      especially to the photobiont, and the distribution of elements in the layers of
      thalli in relation to treatment with heavy metals. We found positive correlations
      between the content of all tested heavy metals and the physiological response. We
      assessed the toxicity of the selected metals as follows: Cd >= Cu >= Ni > Zn,
      based on the effects on the photobiont layer in the lichen thallus and
      physiological measurements.

PMID- 28763758
TI  - Simultaneous determination of three di-caffeoylquinic acids by UHPLC-MS/MS in rat
      plasma and its application to a comparative pharmacokinetic study in normal and
      acute lung injury rat.
AB  - Acute lung injury (ALI) is a severe inflammatory disease with high mortality
      rates. Di-caffeoylquinic acids (DCQAs), the bioactive components of reduning
      injection (RDN), may play important roles in the protective effect on acute lung
      injury (ALI). A selective and rapid ultra high performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS/MS) method has been developed and validated
      for the simultaneous determination of 3,4-, 3,5- and 4,5-DCQA in rat plasma. The
      DCQAs were extracted by liquid-liquid extraction with ethyl acetate-isopropyl
      alcohol (7:3, v/v). Chromatographic separation was accomplished on a C18 column
      using gradient elution. Detection was performed in the multiple reaction
      monitoring (MRM) mode. The lower limits of quantification were all 2.0ng/mL for
      the three analytes. Intra-day and inter-day precision were less than 15% and
      accuracy ranged from -13.8% to 10.0%, and the mean extraction recoveries of
      analytes from rat plasma were all more than 72.9%. Meanwhile, this method had
      been successfully applied to compare the pharmacokinetics of the three DCQAs in
      normal and ALI model rat after RDN was given intravenously administration. The
      pharmacokinetic parameters of the 3,4-, 3,5- and 4,5- DCQA were remarkably
      different from those in normal rats. It might result from the effects of the
      pathological status of ALI. This study presented a meaningful basis for the
      clinical applications of RDN when used in the treatment of ALI.

PMID- 28763759
TI  - Metabolomics analysis of Danggui Sini decoction on treatment of collagen-induced
      arthritis in rats.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by
      persistent joint inflammation leading to bone and cartilage damage and even
      disability. However, the pathogenesis of RA is multi-factorial and to a large
      degree, remains unknown. Danggui Sini decoction (DSD), a traditional Chinese
      medicine (TCM) formula, has been widely used as a remedy for rheumatoid arthritis
      (RA) in recent years. In our study, 1H-nuclear magnetic resonance (1H NMR) based
      metabolomics analysis of 7 potential biomarkers, including taurine (1), urea (2),
      betaine (3), pyruvate (4), hippurate (5), succinate (6) and acetone (7) was
      performed to investigate the progression of RA and assess the efficacy of DSD in
      collagen-induced arthritis (CIA) rats. According to pathway analysis using
      identified metabolites and correlation construction, taurine and hypotaurine
      metabolism, gut microbiota metabolism, pyruvate metabolism,
      glycolysis/gluconeogenesis, the citrate cycle (TCA cycle) and lipid metabolism
      were recognized as being the most influenced metabolic pathways associated with
      RA. As a result, deviations of metabolites 1, 3, 4, 5, 6 and 7 in CIA rats were
      improved by DSD, which suggested that DSD mediated the abnormal metabolic
      pathways synergistically. In summary, the efficacy and its underlying therapeutic
      mechanisms of DSD on RA were systematically investigated and expect to provide a
      new insight in relevant studies of other TCM formulas.

PMID- 28763760
TI  - Mineralogy and textures of riebeckitic asbestos (crocidolite): The role of single
      versus agglomerated fibres in toxicological experiments.
AB  - Asbestos may cause adverse effects, but relationship between mineralogy and
      texture of fibres versus toxicity is still lacking. Toxicological studies can be
      interpreted and compared only if quantitative features of fibres are determined.
      Here, riebeckitic ("crocidolite") amphibole fibres were analysed by XRPD, FTIR,
      SEM-EDS and EMP-WDS; only crystals with stochiometry
      A?BNa2C(Fe2+2.5Mg0.5)CFe3+2TSi8O22W(OH)2 are present in the starting material
      used for the experiments. Fibres deposited from solutions of 0.1, 1, 10, 25, 50,
      75 and 100mg/L were counted by image analysis using SEM images. At 0.1 and 1mg/L
      the fibres are well separated, whereas between 1 and 10mg/L they start to
      agglomerate. In-vitro tests performed on fibres deposited at the same mg/L
      concentrations show that the toxic potential follows a curvilinear increasing
      trend with a decreasing rate. Since the range of sizes of single fibres and their
      mineralogy are constant, this decreasing rate can be only attributed to the
      increasing amount of agglomerated fibres. Hence, single versus agglomerated fibre
      population is a factor that cannot be neglected in defining the final adverse
      effects of asbestos. The analytical protocol proposed here is valuable for any
      aero-dispersed dust, in polluted environments, as well as in the interpretation
      of experimental studies.

PMID- 28763761
TI  - Feedforward neural network methodology to characterize thin films by
      Electrostatic Force Microscopy.
AB  - The contribution of the present paper is in introducing a numerical method to
      improve the automatic characterization of thin films by increasing the
      effectiveness of numerical methods that take into account the macroscopic shape
      of the tip. To achieve this objective, we propose the combination of different
      feedforward neural networks architectures adapted to the specific requirements of
      the physical system under study. First, an Adaline architecture is redefined as a
      linear combination of Green functions obtained from the Laplace equation. The
      learning process is also redefined to accurately calculate the electrostatic
      charges inside the tip. We demonstrate that a complete training set for the
      characterization of thin films can be easily obtained by this methodology. The
      characterization of the sample is developed in a second stage where a multilayer
      perceptron is adapted to work efficiently in experimental conditions where some
      experimental data can be lost. We demonstrate that a very efficient strategy is
      to use evolutionary algorithms as training method. By the modulation of the fit
      function, we can improve the network performance in the characterization of thin
      films where some information is missing or altered by experimental noise due to
      the small tip-sample working distances. By doing so, we can discriminate the
      conductive properties of thin films from force curves that have been altered
      explicitly to simulate realistic experimental conditions.

PMID- 28763762
TI  - Selective detection of pyrophosphate anion by a simple Cd(II) based terpyridine
      complex.
AB  - A simple ratiometric terpyridine-Cd(ll) complex was synthesized by the treatment
      of CdCl2 with terpyridine ligand 4'-(4-N,N'-dimethylaminophenyl)-2,2':6',2"
      terpyridine. The synthesized complex was found to act as a selective fluorescent
      chemosensor for pyrophosphate P2O74- (PPi) over other anions like F-, Cl-, Br-,
      CO32-, SO32-, AcO-, NO2-, and H2PO4-. Furthermore, the receptor probe was also
      successfully employed in HeLa cell for PPi detection, which indicates this can be
      used as a chemosensor for cells.

PMID- 28763763
TI  - Fluorescence enhancement via varied long-chain thiol stabilized gold
      nanoparticles: A study of far-field effect.
AB  - Metal enhanced fluorescence of carbon dots has been reported in aqueous solution.
      Moderately fluorescing carbon dots (lambdaex=360nm and lambdaem=440nm) of 6-8nm
      diameters (CDA) have been synthesized from freshly prepared aqueous ascorbic acid
      solution under modified hydrothermal treatment. The CDA fluorescence is quenched
      at the close proximity with gold nanoparticles (AuNPs). Here, a substrate
      specific near-field electric field distribution is pronounced. Anticipating
      distance dependent fluorescence enhancement phenomenon, long-chain aliphatic
      thiol capped AuNPs are introduced to improve fluorescence of moderately
      fluorescing CDAs. The long-chain aliphatic thiols act as spacers between CDA and
      AuNP. Interestingly, the fluorescence of CDA is observed to be enhanced
      successively as the chain lengths of aliphatic thiols are increased. Fluorescing
      CDA, upon excitation, transfers energy to the nearby AuNP and a plasmon is
      induced. This plasmon radiates in the far-field resulting in fluorescence
      enhancement of CDAs. Such an interesting enhancement in emission with metallic
      gold is termed as gold enhanced fluorescence. This far-field effect for
      fluorescence enhancement of CDA particles becomes a general consensus in solution
      with varied long-chain aliphatic amine ligand capped silver nanoparticles
      (AgNPs). Finally, consequence of far-field effect of fluorescence enhancement has
      been observed while derivatized AuNP and AgNP are introduced into the CDA
      solution simultaneously which is described as reinforced fluorescence enhancement
      due to coupled plasmonic radiation.

PMID- 28763765
TI  - Manganese dioxide nanorods intercalated reduced graphene oxide nanocomposite
      toward high performance electrochemical supercapacitive electrode materials.
AB  - The development of manganese dioxide-based nanocomposites as materials for energy
      storage applications is advantageous because of its polymorphism behavior and
      structural flexibility. In this study, manganese dioxide (MnO2) nanorod
      intercalated reduced graphene oxide (rGO) nanocomposite was obtained through a
      simple hydrothermal method and their electrochemical supercapacitance was studied
      in a three electrode half-assembly electrochemical cell. The basic spectroscopic
      and diffraction data including Raman spectroscopy, scanning electron microscopy,
      and transmission electron microscopy were employed to characterize the resulting
      nanocomposite. Cyclic voltammetry and galvanostatic charge-discharge measurements
      were conducted to evaluate the electrochemical supercapacitance of the rGO-MnO2
      nanocomposite electrode. The rGO-MnO2 nanocomposite delivered significantly
      higher capacitance than the P-MnO2 under similar measurement conditions. This
      enhanced supercapacitive performance of the rGO-MnO2 nanocomposite was attributed
      to chemical interactions and the synergistic effect between rGO and MnO2, which
      was helpful in enhancing the electrical conductivity and providing sufficient
      space for electrode/electrolyte contact during the electrochemical reaction.

PMID- 28763766
TI  - Influence of carbon nanoparticle modification on the mechanical and electrical
      properties of epoxy in small volumes.
AB  - The influence of nanoparticle morphology and filler content on the mechanical and
      electrical properties of carbon nanoparticle modified epoxy is investigated
      regarding small volumes. Three types of particles, representing spherical,
      tubular and layered morphologies are used. A clear size effect of increasing true
      failure strength with decreasing volume is found for neat and carbon black
      modified epoxy. Carbon nanotube (CNT) modified epoxy exhibits high potential for
      strength increase, but dispersion and purity are critical. In few layer graphene
      modified epoxy, particles are larger than statistically distributed defects and
      initiate cracks, counteracting any size effect. Different toughness increasing
      mechanisms on the nano- and micro-scale depending on particle morphology are
      discussed based on scanning electron microscopy images. Electrical percolation
      thresholds in the small volume fibres are significantly higher compared to bulk
      volume, with CNT being found to be the most suitable morphology to form
      electrical conductive paths. Good correlation between electrical resistance
      change and stress strain behaviour under tensile loads is observed. The results
      show the possibility to detect internal damage in small volumes by measuring
      electrical resistance and therefore indicate to the high potential for using CNT
      modified polymers in fibre reinforced plastics as a multifunctional, self
      monitoring material with improved mechanical properties.

PMID- 28763767
TI  - Zero-valent iron nanoparticles embedded into reduced graphene oxide-alginate
      beads for efficient chromium (VI) removal.
AB  - Zero-valent iron nanoparticles (Fe0 NPs) technologies are often challenged by
      poor dispersibility, chemical instability to oxidation, and mobility during
      processing, storage and use. This work reports a facile approach to synthesize
      Fe0 NPs embedded reduced graphene oxide-alginate beads (Fe@GA beads) via the
      immobilization of pre-synthesized Fe0 NPs into graphene oxide modified alginate
      gel followed by a modelling and in-situ reduction process. The
      structure/composition characterization of the beads finds that the graphene
      sheets and the Fe0 NPs (a shape of ellipsoid and a size of <100nm) are uniformly
      dispersed within the alginate beads. We demonstrate that these Fe@GA beads show a
      robust performance in aqueous Cr(VI) removal. With a optimized Fe and alginate
      content, Fe@GA bead can achieve a high Cr(VI) removal efficiency and an excellent
      mechanical strength. The initial Cr(VI) concentration, ionic strength,
      temperature and especially solution pH are all critical factors to control the
      Fe@GA beads performance in Cr(VI) removal. Fitness of the pseudo second-order
      adsorption model with data suggests adsorption is the rate-controlling step, and
      both Langmuir and Freundlich adsorption isotherm are suitable to describe the
      removal behavior. The possible Cr(VI) removal path by Fe@GA beads is put forward,
      and the synergistic effect in this ternary system implies the potentials of Fe@GA
      beads in pollutant removal from water body.

PMID- 28763764
TI  - Proteostasis, oxidative stress and aging.
AB  - The production of reactive species is an inevitable by-product of metabolism and
      thus, life itself. Since reactive species are able to damage cellular structures,
      especially proteins, as the most abundant macromolecule of mammalian cells,
      systems are necessary which regulate and preserve a functional cellular protein
      pool, in a process termed "proteostasis". Not only the mammalian protein pool is
      subject of a constant turnover, organelles are also degraded and rebuild. The
      most important systems for these removal processes are the "ubiquitin-proteasomal
      system" (UPS), the central proteolytic machinery of mammalian cells, mainly
      responsible for proteostasis, as well as the "autophagy-lysosomal system", which
      mediates the turnover of organelles and large aggregates. Many age-related
      pathologies and the aging process itself are accompanied by a dysregulation of
      UPS, autophagy and the cross-talk between both systems. This review will describe
      the sources and effects of oxidative stress, preservation of cellular protein-
      and organelle-homeostasis and the effects of aging on proteostasis in mammalian
      cells.

PMID- 28763768
TI  - Electrochemical selective ion separation in capacitive deionization with sodium
      manganese oxide.
AB  - Electrochemical selective ion separation via capacitive deionization, for
      example, separation of lithium resource from brine, using lithium ion batteries
      is proposed and demonstrated to have the potential for separating specific ions
      selectively from a solution containing diverse ions. This separation method is of
      great industrial concern because of applicability in various fields such as
      deionization, water softening, purification, heavy metal removal, and resource
      recovery. Nevertheless, besides the selectivity of materials for lithium ion
      batteries toward Li+, there is very little investigation on the selectivity of
      the materials for sodium ion batteries toward Na+. Here, the electrochemical
      selectivity of sodium manganese oxide (Na0.44MnO2), one of the most widely used
      material in sodium ion batteries, for Na+ and other cations (K+, Mg2+, and Ca2+)
      is investigated. Selective Na+ separation using the system consisting of
      Na0.44MnO2 and a Ag/AgCl electrode is successfully demonstrated from a solution
      containing diverse cations (Na+, K+, Mg2+, and Ca2+) via a two-step process that
      involves a capturing step (charging process) and a releasing step (discharging
      process). The results showed that Na0.44-xMnO2 has over 13 times higher
      selectivity for Na+ than for K+ and 6-8times higher selectivity for Na+ than for
      Mg2+ and Ca2+ in the electrolyte containing equal concentrations of the
      respective ions. Additionally, as a practical demonstration, Na+ was successfully
      separated from an industrial raw material used for pure KOH production (estimated
      ratio of Na+:K+=1:200).

PMID- 28763769
TI  - Robust, heat-resistant and multifunctional superhydrophobic coating of carbon
      microflowers with molybdenum trioxide nanoparticles.
AB  - Superhydrophobic materials have triggered large interest due to their widespread
      applications, such as self-cleaning, corrosion resistance, anti-icing, and
      oil/water separation. However, suffering from weak mechanical strength, plenty of
      superhydrophobic materials are limited in practical application. Herein, we
      prepared hierarchical carbon microflowers (CMF) dispersed with molybdenum
      trioxide (MoO3) nanoparticles (MoO3/CMF) via a two-step preparation method.
      Taking advantage of high-adhesion epoxy resin and the modification with
      1H,1H,2H,2H-perfluorodecyltriethoxysilane (PDES), the modified MoO3/CMF (PDES
      MoO3/CMF) coating on various substrates shows great waterproof ability, excellent
      chemical stability, good mechanical durability, and self-cleaning property. More
      significantly, the prepared PDES-MoO3/CMF powder with high thermal stability (250
      degrees C) can be used for oil/water separation due to its special flower-like
      structure and superhydrophobicity/superoleophilicity. All of these advantages
      endow the superhydrophobic powders with huge potential in the practical
      applications.

PMID- 28763770
TI  - Facile synthesis of a two-tier hierarchical structured superhydrophobic
      superoleophilic melamine sponge for rapid and efficient oil/water separation.
AB  - Oil leakages often cause fatal disasters for environmental pollution but an
      efficient treatment of the oil spills is still very challenging. Sponge
      substrates with superhydrophobicity and superoleophilicity have been attracted
      much attention for oil/water separation. In this study, an inexpensive commercial
      melamine sponge was chemically modified for the uses of oil spills treatment by
      oil/water separation. Inspiring from the superhydrophobic property of lotus leaf,
      pyrrole was polymerized by a simple vapor-phase deposition to encapsulate the raw
      melamine-formaldehyde (MF) sponge. The as-formed thin polypyrrole walls were
      utilized as reducing reagent to generate Ag nanoparticles on the capsuled sponge.
      Accordingly, a superhydrophobic melamine sponge with a two-tier hierarchical
      structure was achieved after fluorination, and this material was applied to
      absorb oil from water. The absorption capacity, absorption rate and recyclability
      were investigated. This superhydrophobic sponge exhibited an efficient and fast
      oil/water separation performance in complicated environment and could be applied
      in industrial production because of its low cost and simple fabrication
      procedure. This study presents a facile strategy for the fabrication of efficient
      oil sorbents based on a two-tier hierarchical structure, providing a novel means
      for the upgrading of engineered sorption materials.

PMID- 28763771
TI  - Taurine grafting and collagen adsorption on PLLA films improve human primary
      chondrocyte adhesion and growth.
AB  - Biocompatible and degradable poly(alpha-hydroxy acids) are one of the most widely
      used materials in scaffolds for tissue engineering. Nevertheless, they often need
      surface modification to improve interaction with cells. Aminolysis is a common
      method to increase the polymer hydrophilicity and to introduce surface functional
      groups, able to covalently link or absorb, through electrostatic interaction,
      bioactive molecules or macromolecules. For this purpose, multi-functional amines,
      such as diethylenediamine or hexamethylenediamine are used. However, common
      drawbacks are their toxicity and the introduction of positive charges on the
      surface. Thus, these kind of modified surfaces are unable to link directly
      proteins, such as collagens, a promising substrate for many cell types, in
      particular chondrocytes and osteoblasts. In this work, poly(L-lactide) (PLLA)
      film surface was labelled with negatively charged sulfonate groups by grafting
      taurine (TAU) through an aminolysis reaction. The novel modified PLLA film (PLLA
      TAU) was able to interact directly with collagen. The reaction was carried out in
      mild conditions by using a solution of tetrabutylammonium salt of TAU in
      methanol. ATR-FTIR, XPS and contact angle measurements were used to verify the
      outcome of the reaction. After the exchange of tetrabutylamonium cation with Na+,
      collagen was absorbed on the TAU grafted PLLA film (PLLA-TAU-COLL). In vitro
      biological tests with human primary chondrocytes showed that PLLA-TAU and PLLA
      TAU-COLL improved cell viability and adhesion, compared to the unmodified
      polymer, suggesting that these modifications make PLLA substrate suitable for
      cartilage repair.

PMID- 28763772
TI  - pH-responsive chitosan nanoparticles from a novel twin-chain anionic amphiphile
      for controlled and targeted delivery of vancomycin.
AB  - The design and synthesis of novel pH-responsive nanoantibiotics is an emerging
      research area to address the antibiotic resistance crisis. The purpose of this
      study was therefore to synthesize a new anionic gemini surfactant (AGS) that
      could result in the formulation of pH-responsive chitosan nanoparticles (CSNPs)
      to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. The
      coupling of oleic acid with 2,2-dimethyl-5,5-bis(hydroxymethyl)-1,3-dioxane and
      subsequent deprotection followed by a reaction with succinic anhydride and sodium
      bicarbonate yielded AGS. Critical micelle concentration (CMC) was determined
      using conductometry and in vitro cytotoxicity was performed using a MTT assay.
      Vancomycin loaded CSNPs containing AGS (DL_CSSNPs) were prepared by ionotropic
      gelation of chitosan with pentasodium tripolyphosphate. CSNPs were characterized
      for size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency,
      surface morphology, in vitro drug release and in vitro antibacterial activity (at
      pH 6.5 and 7.4). Results from the in vitro antibacterial activity were further
      supported by an in vivo study using a mice skin infection model. The CMC of AGS
      was found to be 1.3mM/L and it was non-toxic. The DL_CSSNPs were spherical with
      size, PDI and ZP of 220.57+/-5.9nm, 0.299+/-0.004 and 21.9+/-0.9mV respectively.
      An increase in the vancomycin release from the DL_CSSNPs was observed at pH 6.5
      compared to pH 7.4. The minimum inhibitory concentration values at pH 6.5 and 7.4
      against MRSA were 7.81 and 62.5MUg/ml respectively. In vivo antibacterial
      activity showed that the MRSA burden in mice treated with DL_CSSNPs was reduced
      by almost 8-fold compared to those treated with pure vancomycin.

PMID- 28763773
TI  - Polyion complex vesicles (PICsomes) from strong copolyelectrolytes. Stability and
      in vitro studies.
AB  - Polymer vesicles formed by a pair of oppositely charged diblock
      copolyelectrolytes (PICsomes) are considered as a good alternative to
      polymersomes formed by amphiphilic copolymers. Here, we report on inherent
      stability and in vitro biocompatibility of PICsomes prepared from a pair of
      oppositely charged zwitterionic-ionic copolymers, in which the ionic block is a
      strong polyelectrolyte. Our results demonstrated that the PICsomes are highly
      stable over a wide range of pH and temperatures. Direct microscopic observations
      revealed that the PICsomes retain their morphology in the presence of human
      serum. In vitro studies using human skin fibroblasts (HSFs) showed that the
      polymer vesicles are not cytotoxic and do not affect cell proliferation and
      adhesion. A model hydrophilic dye was effectively incorporated into the PICsomes
      by simple mixing. Using confocal microscopy observations, we demonstrated that
      the dye-loaded PICsomes are efficiently internalized by the cells and are located
      predominantly in endo/lysosomal compartments. Thus, the PICsomes have promising
      potential for use as nanocontainers for substances of biomedical interest.

PMID- 28763774
TI  - Properties of POPC/POPE supported lipid bilayers modified with hydrophobic
      quantum dots on polyelectrolyte cushions.
AB  - The formation and properties of supported lipid bilayers (SLB) containing
      hydrophobic nanoparticles (NP) was studied in relation to underlying cushion
      obtained from selected polyelectrolyte multilayers. Lipid vesicles were formed
      from zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and
      negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE)
      in phosphate buffer (PBS). As hydrophobic nanoparticles - quantum dots (QD) with
      size of 3.8nm (emission wavelength of 420nm) were used. Polyelectrolyte
      multilayers (PEM) were constructed by the sequential, i.e., layer-by-layer (LbL)
      adsorption of alternately charged polyelectrolytes from their solutions.
      Liposomes and Liposome-QDs complexes were studied with Transmission Cryo-Electron
      Microscopy (Cryo-TEM) to verify the quality of vesicles and the position of QD
      within lipid bilayer. Deposition of liposomes and liposomes with quantum dots on
      polyelectrolyte films was studied in situ using quartz crystal microbalance with
      dissipation (QCM-D) technique. The fluorescence emission spectra were analyzed
      for both: suspension of liposomes with nanoparticles and for supported lipid
      bilayers containing QD on PEM. It was demonstrated that quantum dots are located
      in the hydrophobic part of lipid bilayer. Moreover, we proved that such QD
      modified liposomes formed supported lipid bilayers and their final structure
      depended on the type of underlying cushion.

PMID- 28763775
TI  - Heat indicators of oxidative stress, inflammation and metal transport show
      dependence of cadmium pollution history in the liver of female zebrafish.
AB  - Environmental stressors such as high temperature and metal exposure may occur
      sequentially, simultaneously, previously in aquatic ecosystems. However,
      information about whether responses to high temperature depend on Cd exposure
      history is still unknown in fish. Zebrafish were exposed to 0 (group 1), 2.5
      (group 2) and 5MUg/L (group 3) cadmium (Cd) for 10 weeks, and then each group was
      subjected to Cd-free water maintained at 26 degrees C and 32 degrees C for 7days
      respectively. 26 indicators were used to compare differences between 26 degrees C
      and 32 degrees C in the liver of female zebrafish, including 5 biochemical
      indicators (activity of Cu/Zn-SOD, CAT and iNOS; LPO; MT protein), 8 molecular
      indicators of oxidative stress (mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2,
      HSP70, MTF-1 and MT), 5 molecular indicators of inflammation (mRNA levels of IL
      6, IL-1beta, TNF-alpha, iNOS and NF-kappaB), 8 molecular indicators of metal
      transport (mRNA levels of, ZnT1, ZnT5, ZIP8, ZIP10, ATP7A, ATP7B and CTR1). All
      biochemical indicators were unchanged in group 1 and changed in group 2 and 3.
      Contrarily, differences were observed in almost all of molecular indicators of
      inflammation and metal transport in group 1, about half in group 2, and few in
      group 3. We also found that all molecular indicators of oxidative stress in group
      2 and fewer in group 1 and 3 were significantly affected by heat. Our data
      indicated that heat indicators of oxidative stress, inflammation and metal
      transport showed dependence of previous cadmium exposure in the liver of
      zebrafish, emphasizing metal pollution history should be carefully considered
      when evaluating heat stress in fish.

PMID- 28763776
TI  - A comparative experimental approach to ecotoxicology in shallow-water and deep
      sea holothurians suggests similar behavioural responses.
AB  - Exploration of deep-sea mineral resources is burgeoning, raising concerns
      regarding ecotoxicological impacts on deep-sea fauna. Assessing toxicity in deep
      sea species is technologically challenging, which promotes interest in
      establishing shallow-water ecotoxicological proxy species. However, the effects
      of temperature and hydrostatic pressure on toxicity, and how adaptation to deep
      sea environmental conditions might moderate these effects, are unknown. To
      address these uncertainties we assessed behavioural and physiological
      (antioxidant enzyme activity) responses to exposure to copper-spiked artificial
      sediments in a laboratory experiment using a shallow-water holothurian
      (Holothuria forskali), and in an in situ experiment using a deep-sea holothurian
      (Amperima sp.). Both species demonstrated sustained avoidance behaviour, evading
      contact with contaminated artificial sediment. However, A. sp. demonstrated
      sustained avoidance of 5mgl-1 copper-contaminated artificial sediment whereas H.
      forskali demonstrated only temporary avoidance of 5mgl-1 copper-contaminated
      artificial sediment, suggesting that H. forskali may be more tolerant of metal
      exposure over 96h. Nonetheless, the acute behavioural response appears consistent
      between the shallow-water species and the deep-sea species, suggesting that H.
      forskali may be a suitable ecotoxicological proxy for A. sp. in acute (<=24h)
      exposures, which may be representative of deep-sea mining impacts. No antioxidant
      response was observed in either species, which was interpreted to be the
      consequence of avoiding copper exposure. Although these data suggest that shallow
      water taxa may be suitable ecotoxicological proxies for deep-sea taxa,
      differences in methodological and analytical approaches, and in sex and
      reproductive stage of experimental subjects, require caution in assessing the
      suitability of H. forskali as an ecotoxicological proxy for A. sp. Nonetheless,
      avoidance behaviour may have bioenergetic consequences that affect growth and/or
      reproductive output, potentially impacting fecundity and/or offspring fitness,
      and thus influencing source-sink dynamics and persistence of wider deep-sea
      populations.

PMID- 28763777
TI  - Structural deficits in salience network regions are associated with increased
      impulsivity and compulsivity in alcohol dependence.
AB  - BACKGROUND: Convergent preclinical and clinical evidence has linked the anterior
      insula to impulsivity and alcohol-associated compulsivity. The anterior insula is
      functionally connected to the anterior cingulate cortex, together comprising the
      major nodes of the salience network, which serves to signal salient events,
      including negative consequences. Clinical studies have found structural and
      functional alterations in the anterior insula and anterior cingulate cortices of
      alcohol dependent individuals. No studies have yet investigated the association
      between morphometric abnormalities in salience network regions and the phenotype
      of high levels of impulsivity and compulsivity seen in alcohol dependent
      individuals. METHODS: In the current study, we compared self-report impulsivity,
      decisional impulsivity, self-report compulsivity, and structural neuroimaging
      measures in a sample of alcohol dependent individuals (n=60) and a comparison
      group of healthy controls (n=49). From the structural magnetic resonance images,
      we calculated volume and cortical thickness for 6 regions of interest: left and
      right anterior insula, posterior insula, and anterior cingulate. RESULTS: We
      found that alcohol dependent individuals had smaller anterior insula and anterior
      cingulate volumes, as well as thinner anterior insula cortices. There were no
      group differences in posterior insula morphometry. Anterior insula and anterior
      cingulate structural measures were negatively associated with self-report
      impulsivity, decisional impulsivity, and compulsivity measures. CONCLUSIONS: Our
      results suggest that addiction endophenotypes are associated with salience
      network morphometry in alcohol addiction. These relationships indicate that
      salience network hubs represent potential treatment targets for impulse control
      disorders, including alcohol addiction.

PMID- 28763779
TI  - Prefrontal Glx and GABA concentrations and impulsivity in cigarette smokers and
      smoking polysubstance users.
AB  - Glutamate and GABA play an important role in substance dependence. However, it
      remains unclear whether this holds true for different substance use disorders and
      how this is related to risk-related traits such as impulsivity. We, therefore,
      compared Glx (as a proxy measure for glutamate) and GABA concentrations in the
      dorsal anterior cingulate cortex (dACC) of 48 male cigarette smokers, 61 male
      smoking polysubstance users, and 90 male healthy controls, and investigated the
      relationship with self-reported impulsivity and substance use. Glx and GABA
      concentrations were measured using proton Magnetic Resonance Spectroscopy.
      Impulsivity, smoking, alcohol and cocaine use severity and cannabis use were
      measured using self-report instruments. Results indicate a trend towards group
      differences in Glx. Post-hoc analyses showed a difference between smokers and
      healthy controls (p=0.04) and a trend towards higher concentrations in smoking
      polysubstance users and healthy controls (p=0.09), but no differences between
      smokers and smoking polysubstance users. dACC GABA concentrations were not
      significantly different between groups. Smoking polysubstance users were more
      impulsive than smokers, and both groups were more impulsive than controls. No
      significant associations were observed between dACC neurotransmitter
      concentrations and impulsivity and level and severity of smoking, alcohol or
      cocaine use or the presence of cannabis use. The results indicate that
      differences in dACC Glx are unrelated to type and level of substance use. No
      final conclusion can be drawn on the lack of GABA differences due to assessment
      difficulties. The relationship between dACC neurotransmitter concentrations and
      cognitive impairments other than self-reported impulsivity should be further
      investigated.

PMID- 28763780
TI  - Treatment use, sources of payment, and financial barriers to treatment among
      individuals with opioid use disorder following the national implementation of the
      ACA.
AB  - INTRODUCTION: Despite increasing rates of opioid misuse and hospitalizations,
      rates of treatment for those with opioid use disorder (OUD) are very low. This
      study examined the impact of the Patient Protection and Affordable Care Act's
      (ACA) insurance expansion on improving rates of insurance, health care access,
      and treatment for those with OUD. METHODS: Data on individuals ages 18-64 with
      OUD come from the 2008-2014 National Survey on Drug Use and Health (N=4100).
      Multivariable logistic regression analyses were performed to estimate the trends
      of health care insurance, treatment and barriers to care across the stages of ACA
      implementation: pre-ACA (2008-2009), partial-ACA (2010-2013), and national
      implementation (2014). All models were adjusted for predisposing, enabling, and
      need factors. RESULTS: In both adjusted and unadjusted comparisons, national
      implementation of the ACA was associated with significant improvements in outcome
      measures for those with OUD. Multivariable analyses indicate that, after national
      implementation, those with OUD were significantly less likely to be uninsured and
      were less likely to report financial barriers as a reason for not receiving
      substance use treatment, relative to the pre-ACA period. Individuals were also
      more likely to receive substance use treatment and were more likely to report
      that insurance paid for treatment after national implementation of the ACA
      relative to the pre-ACA period. These results persisted when national
      implementation was compared relative to partial-implementation. CONCLUSIONS:
      National implementation of the ACA has helped to reduce rates of uninsurance,
      barriers to care, and improve rates of substance use treatment for those with
      OUD.

PMID- 28763778
TI  - The association between regular marijuana use and adult mental health outcomes.
AB  - OBJECTIVE: The present study is a prospective examination of the relationship
      between regular marijuana use from adolescence through young adulthood and mental
      health outcomes at age 33. METHODS: Data came from a gender-balanced, ethnically
      diverse longitudinal panel of 808 participants from Seattle, Washington. Outcomes
      included symptom counts for six mental health disorders. Regular marijuana use
      was tracked during adolescence and young adulthood. Regression analyses
      controlled for demographics and early environment, behaviors, and individual risk
      factors. RESULTS: Nonusers of marijuana reported fewer symptoms of alcohol use
      disorder, nicotine dependence, and generalized anxiety disorder than any category
      of marijuana users. More persistent regular marijuana use in young adulthood was
      positively related to more symptoms of cannabis use disorder, alcohol use
      disorder, and nicotine dependence at age 33. CONCLUSIONS: Findings highlight the
      importance of avoiding regular marijuana use, especially chronic use in young
      adulthood. Comprehensive prevention and intervention efforts focusing on
      marijuana and other substance use might be particularly important in the context
      of recent legalization of recreational marijuana use in Washington and other U.S.
      states.

PMID- 28763781
TI  - Past year cannabis use and problematic cannabis use among adults by ethnicity in
      Ontario.
AB  - BACKGROUND: Rates of cannabis use differ around the world; in Ontario, the rate
      of use has been stable since about 2005. Understanding which population groups
      are at greater risk for problematic cannabis use can help reduce long-term health
      effects and service expenses. The aim of this study was to explore differences in
      cannabis use among Canadian adults of different ethnic origins living in Ontario.
      METHODS: Data are based on telephone interviews with 11,560 respondents and are
      derived from multiple cycles (2005-2011) of the Centre for Addiction and Mental
      Health's (CAMH) Monitor survey, an ongoing cross-sectional survey of adults in
      Ontario, Canada, aged 18 years and older. Data were analyzed using bivariate
      cross-tabulations and logistic regression. Problematic cannabis use was
      determined with a score of 8+ on the ASSIST-CIS to identify moderate/high
      problematic users. RESULTS: Lifetime, past year and problematic cannabis use (in
      the past 3 months) occurs among all ethnic groups: Canadian, East Asian, South
      East Asian, South Asian, Caribbean, African, East European, South European, North
      European, and Central West European. When compared to the Canadian group the odds
      of past year cannabis use was significantly lower for East Asians and South
      Asians, but higher for the Caribbean group. Significantly higher odds of
      problematic cannabis use were found for Caribbeans and Northern Europeans
      compared to Canadians. CONCLUSIONS: These results of this study provide an
      important basis for considering the possible impact of the impending legalization
      of cannabis in Canada among different ethnic groups.

PMID- 28763782
TI  - Molecular imprinting coupled with electrochemical analysis for plasma samples
      classification in acute myocardial infarction diagnostic.
AB  - Electroanalysis of myoglobin (Mb) in 10 plasma samples of healthy donors (HDs)
      and 14 plasma samples of patients with acute myocardial infarction (AMI) was
      carried out with screen-printed electrodes modified first with multi-walled
      carbon nanotubes (MWCNT) and then with a molecularly imprinted polymer film
      (MIP), viz., myoglobin-imprinted electropolymerized poly(o-phenylenediamine). The
      differential pulse voltammetry (DPV) parameters, such as a maximum amplitude of
      reduction peak current (A, nA), a reduction peak area (S, nA * V), and a peak
      potential (P, V), were measured for the MWCNT/MIP-sensors after their incubation
      with non-diluted plasma. The relevance of the multi-parameter electrochemical
      data for accurate discrimination between HDs and patients with AMI was assessed
      on the basis of electrochemical threshold values (this requires the reference
      standard method (RAMP(r) immunoassay)) or alternatively on the basis of the
      computational cluster assay (this does not require any reference standard
      method). The multi-parameter electrochemical analysis of biosamples combined with
      computational cluster assay was found to provide better accuracy in
      classification of plasma samples to the groups of HDs or AMI patients.

PMID- 28763783
TI  - A highly stable acetylcholinesterase biosensor based on chitosan-TiO2-graphene
      nanocomposites for detection of organophosphate pesticides.
AB  - A highly stable electrochemical acetylcholinesterase (AChE) biosensor for
      detection of organophosphorus pesticides (OPs) was developed simply by adsorption
      of AChE on chitosan (CS), TiO2 sol-gel, and reduced graphene oxide (rGO) based
      multi-layered immobilization matrix (denoted as CS@TiO2-CS/rGO). The biosensor
      fabrication conditions were optimized, and the fabrication process was probed and
      confirmed by scanning electron microscopy and electrochemical techniques. The
      matrix has a mesoporous nanostructure. Incorporation of CS and electrodeposition
      of a CS layer into/on the TiO2 sol-gel makes the gel become mechanically strong.
      The catalytic activity of the AChE immobilized CS@TiO2-CS/rGO/glassy carbon
      electrode to acetylthiocholine is significantly higher than those missing any one
      of the component in the matrix. The detection linear range of the biosensor to
      dichlorvos, a model OP compound, is from 0.036MUM (7.9 ppb) to 22.6MUM, with a
      limit of detection of 29nM (6.4 ppb) and a total detection time of about 25min.
      The biosensor is very reproducibly and stable both in detection and in storage,
      and can accurately detect the dichlorvos levels in cabbage juice samples,
      providing an efficient platform for immobilization of AChE, and a promisingly
      applicable OPs biosensor with high reliability, simplicity, and rapidness.

PMID- 28763784
TI  - Liposome-amplified photoelectrochemical immunoassay for highly sensitive
      monitoring of disease biomarkers based on a split-type strategy.
AB  - Liposomes are an excellent candidate component for biosensors to transduce and
      amplify detection signals due to their outstanding ability in encapsulating
      signal marker compounds. However, the use of liposomes for photoelectrochemical
      (PEC) signal transduction has not yet been achieved due the lack of appropriate
      sensing strategy. Herein, we report on a novel liposomes-amplified PEC
      immunoassay (LAPIA) method for sensitive HIV-p24 antigen (p24) detection based on
      a split-type strategy. Initially, liposomes were encapsulated with alkaline
      phosphatase (ALP) in their hydrophilic chamber and conjugated with secondary
      antibody on the surface to form the ALP-encapsulated liposomes (ALP-Ls) based PEC
      signal label. Sandwiched immunoassay based on the ALP-Ls label was then carried
      out in microwell plate. Upon addition of tween 20, the ALP molecules were
      released and catalyzed the hydrolysis of ascorbic acid 2-phosphate (AA-p) to
      produce ascorbic acid (AA). The latter then donated electron to the graphene/g
      C3N4 nanohybrids based photoelectrode, arousing an increased photocurrent signal.
      The separation of immunoreaction step and PEC signal excitation (i.e. split-type)
      not only enabled the realization of liposomes based amplification strategy, but
      also could eliminate the PEC-caused biomolecules damage. The developed PEC method
      possessed a wide calibration range from 1.0pgmL-1 to 50ngmL-1 and a low detection
      limit of 0.63pgmL-1. Its practicability was demonstrated by assaying human serum
      samples. Moreover, the universality of the liposomes-amplified PEC sensing
      strategy was also demonstrated by developing it into a sensitive microRNA
      detection method.

PMID- 28763785
TI  - Analytical, thermodynamical and kinetic characteristics of photoluminescence
      immunosensor for the determination of Ochratoxin A.
AB  - Ochratoxin A (OTA) is one of the most widespread and dangerous food contaminants.
      Therefore, rapid, label-free and precise detection of low OTA concentrations
      requires novel sensing elements with advanced bio-analytical properties. In the
      present paper we report photoluminescence (PL) based immunosensor for the
      detection of OTA. During the development of immunosensor photoluminescent ZnO
      nanorods (ZnO-NRs) were deposited on glass substrate. Then the ZnO-NRs were
      silanized and covalently modified by Protein-A (Glass/ZnO-NRs/Protein-A). The
      latest structure was modified by antibodies against OTA (Anti-OTA) in order to
      form OTA-selective layer (Glass/ZnO-NRs/Protein-A/Anti-OTA). In order to improve
      immunosensors selectivity the surface of Glass/ZnO-NRs/Protein-A/Anti-OTA was
      additionally blocked by BSA. Formed Glass/ZnO-NRs/Protein-A/BSA&Anti-OTA
      structures were integrated within portable fiber optic detection system, what is
      important for the development of low cost and portable immunosensors. The
      immunosensor has been tested in a wide range of OTA concentrations from 10-4ng/ml
      until 20ng/ml. Interaction isotherms were derived from analytical signals of
      immunosensor. Association constant and Gibbs free energy for the interaction of
      Glass/ZnO-NRs/Protein-A/Anti-OTA with OTA were calculated, analyzed and compared
      with some other related results. Sensitivity range and limit of detection were
      determined as 0.1-1ng/ml and 10-2ng/ml, respectively. Interaction kinetics of ZnO
      NRs with OTA was evaluated. Response time of the immunosensor toward OTA was in
      the range of 500-800s. Some insights related to the mechanism of PL-signal
      generation are proposed and discussed.

PMID- 28763786
TI  - Child maltreatment in Nepal: prevalence and associated factors.
AB  - OBJECTIVES: Child maltreatment is a global public health problem. There is
      limited information about this problem in low-income countries. We aimed to
      document the prevalence and factors associated with physical punishment of
      children less than 14 years of age in Nepal. STUDY DESIGN: Population-based cross
      sectional study. METHODS: We conducted an in-depth analysis using data from the
      Nepal Multiple Indicator Cluster Survey, a nationally representative multi-stage
      stratified cluster sampling survey. Data were collected from 13,000 households in
      520 sample enumeration areas. We assessed prevalence of physical punishment and
      different child violence related acts on 5081 children aged 3-14 years for whom
      complete information on all acts and attitude towards violence was available.
      Logistic regression was used to investigate the association between physical
      punishment of child and factors such as household and maternal demographics.
      RESULTS: Our results suggested violence is common across Nepal, with data showing
      one in every second child is physically punished. One in every third (33%) of
      children were spanked, hit or slapped on the bottom, 25% were hit or slapped on
      the face and approximately 3% were beaten up hard. Odds of facing physical
      punishment were higher among children aged 3-5 years (odds ratio [OR] 2.9, 95%
      confidence interval [CI]: 2.0-4.3), aged 6-8 years (OR 2.8, 95% CI: 2.2-3.7),
      engaged in child labour activities (OR 1.4, 95% CI: 1.1-1.7), with mother that
      accepted wife beating by husband is justified (OR 1.2, 95% CI: 1.1-1.4), whose
      father is currently abroad (OR 1.5, 95% CI: 1.2-1.9) and whose father is away
      from home but in the same country (OR 1.60, 95% CI: 1.1-2.3). The risk was also
      higher among children living in households that believe physical punishment of
      children is necessary (OR 3.5, 95% CI: 2.9-4.3) and from lower caste/indigenous
      (dalit/janajati) ethnicity (OR 1.3, 95% CI: 1.1-1.7). Those less likely to
      experience physical punishment included female children (OR 0.7, 95% CI: 0.6-0.9)
      and children with an older mother (34-49 years; OR 0.5, 95% CI: 0.3-0.9).
      CONCLUSIONS: Our results suggest that physical punishment of children is common
      across Nepal with varying severity. Prevention efforts should focus on designing
      and promoting interventions that support parents to adapt alternative forms of
      parenting practices.

PMID- 28763787
TI  - Replacement of Bonner spheres with polyethylene cylinders for the unfolding of an
      241Am-Be neutron energy spectrum.
AB  - In this study, a conventional Bonner sphere spectrometer, together with 6LiI(Eu)
      inorganic scintillator used as the central detector, was used to obtain the
      neutron energy spectrum of an 241Am-Be source. To achieve this, we calculated the
      response matrices corresponding to eight different sizes of polyethylene spheres
      for the neutron energies ranging from about 10-7 to 15MeV in 54 energy groups by
      using the MCNPX2.6 code, and the 241Am-Be neutron spectrum was obtained using a
      modified version of the neutron spectrum unfolding code, AFITBUNKI. In a
      feasibility study, similar calculations were performed with different sizes of
      polyethylene cylinders. A comparison between the unfolded spectra of a typical
      241Am-Be neutron source with those of Bonner spheres, cylinders of similar sizes,
      and standard 241Am-Be neutron energy spectra shows that the spectrometer with
      polyethylene cylinders can be used as a potential alternative for conventional
      Bonner spheres.

PMID- 28763788
TI  - Measurement of activation cross-section of long-lived products in deuteron
      induced nuclear reactions on palladium in the 30-50MeV energy range.
AB  - Excitation functions were measured in the 31-49.2MeV energy range for the
      natPd(d,xn)111,110m,106m,105,104g,103Ag, natPd(d,x) 111m,109,101,100Pd,
      natPd(d,x), 105,102m,102g,101m,101g,100,99m,99gRh and natPd(d,x)103,97Ru nuclear
      reactions by using the stacked foil irradiation technique. The experimental
      results are compared with our previous results and with the theoretical
      predictions calculated with the ALICE-D, EMPIRE-D and TALYS (TENDL libraries)
      codes.

PMID- 28763789
TI  - Ubiquitination of STING at lysine 224 controls IRF3 activation.
AB  - Cytosolic DNA species derived from invading microbes or leaked from the nuclear
      or mitochondrial compartments of the cell can trigger the induction of host
      defense genes by activating the endoplasmic reticulum-associated protein STING
      (stimulator of interferon genes). Using a mass spectrometry-based approach, we
      show that after association with cyclic dinucleotides, delivery of Tank-binding
      kinase 1 to interferon regulatory factors (IRFs), such as IRF3, relies on K63
      linked ubiquitination of K224 on STING. Blocking K224 ubiquitination specifically
      prevented IRF3 but not nuclear factor kappaB activation, additionally indicating
      that STING trafficking is not required to stimulate the latter signaling pathway.
      By carrying out a limited small interfering RNA screen, we have identified MUL1
      (mitochondrial E3 ubiquitin protein ligase 1) as an E3 ligase that catalyzes the
      ubiquitination of STING on K224. These data demonstrate the critical role of K224
      ubiquitination in STING function and provide molecular insight into the
      mechanisms governing host defense responses.

PMID- 28763791
TI  - Beyond spell checking: Adding function to precision medicine.
AB  - Immunoprofiling signaling pathways in rare immunodeficiencies aid design of
      targeted therapies.

PMID- 28763792
TI  - A Flicr of hope for autoimmunity.
AB  - The long noncoding RNA Flicr modifies Foxp3 chromatin accessibility to reduce T
      regulatory cell differentiation and function.

PMID- 28763790
TI  - Platelets subvert T cell immunity against cancer via GARP-TGFbeta axis.
AB  - Cancer-associated thrombocytosis has long been linked to poor clinical outcome,
      but the underlying mechanism is enigmatic. We hypothesized that platelets promote
      malignancy and resistance to therapy by dampening host immunity. We show that
      genetic targeting of platelets enhances adoptive T cell therapy of cancer. An
      unbiased biochemical and structural biology approach established transforming
      growth factor beta (TGFbeta) and lactate as major platelet-derived soluble
      factors to obliterate CD4+ and CD8+ T cell functions. Moreover, we found that
      platelets are the dominant source of functional TGFbeta systemically as well as
      in the tumor microenvironment through constitutive expression of the TGFbeta
      docking receptor glycoprotein A repetitions predominant (GARP) rather than
      secretion of TGFbeta per se. Platelet-specific deletion of the GARP-encoding gene
      Lrrc32 blunted TGFbeta activity at the tumor site and potentiated protective
      immunity against both melanoma and colon cancer. Last, this study shows that T
      cell therapy of cancer can be substantially improved by concurrent treatment with
      readily available antiplatelet agents. We conclude that platelets constrain T
      cell immunity through a GARP-TGFbeta axis and suggest a combination of
      immunotherapy and platelet inhibitors as a therapeutic strategy against cancer.

PMID- 28763793
TI  - Virion incorporation of integrin alpha4beta7 facilitates HIV-1 infection and
      intestinal homing.
AB  - The intestinal mucosa is a key anatomical site for HIV-1 replication and CD4+ T
      cell depletion. Accordingly, in vivo treatment with an antibody to the gut-homing
      integrin alpha4beta7 was shown to reduce viral transmission, delay disease
      progression, and induce persistent virus control in macaques challenged with
      simian immunodeficiency virus (SIV). We show that integrin alpha4beta7 is
      efficiently incorporated into the envelope of HIV-1 virions. Incorporated
      alpha4beta7 is functionally active as it binds mucosal addressin cell adhesion
      molecule-1 (MAdCAM-1), promoting HIV-1 capture by and infection of MAdCAM
      expressing cells, which in turn mediate trans-infection of bystander cells.
      Functional alpha4beta7 is present in circulating virions from HIV-infected
      patients and SIV-infected macaques, with peak levels during the early stages of
      infection. In vivo homing experiments documented selective and specific uptake of
      alpha4beta7+ HIV-1 virions by high endothelial venules in the intestinal mucosa.
      These results extend the paradigm of tissue homing to a retrovirus and are
      relevant for the pathogenesis, treatment, and prevention of HIV-1 infection.

PMID- 28763794
TI  - Targeting latency-associated peptide promotes antitumor immunity.
AB  - Regulatory T cells (Tregs) promote cancer by suppressing antitumor immune
      responses. We found that anti-LAP antibody, which targets the latency-associated
      peptide (LAP)/transforming growth factor-beta (TGF-beta) complex on Tregs and
      other cells, enhances antitumor immune responses and reduces tumor growth in
      models of melanoma, colorectal carcinoma, and glioblastoma. Anti-LAP decreases
      LAP+ Tregs, tolerogenic dendritic cells, and TGF-beta secretion and is associated
      with CD8+ T cell activation. Anti-LAP increases infiltration of tumors by
      cytotoxic CD8+ T cells and reduces CD103+ CD8 T cells in draining lymph nodes and
      the spleen. We identified a role for CD103+ CD8 T cells in cancer. Tumor
      associated CD103+ CD8 T cells have a tolerogenic phenotype with increased
      expression of CTLA-4 and interleukin-10 and decreased expression of interferon
      gamma, tumor necrosis factor-alpha, and granzymes. Adoptive transfer of CD103+
      CD8 T cells promotes tumor growth, whereas CD103 blockade limits tumorigenesis.
      Thus, anti-LAP targets multiple immunoregulatory pathways and represents a
      potential approach for cancer immunotherapy.

PMID- 28763795
TI  - Intratumoral delivery of inactivated modified vaccinia virus Ankara (iMVA)
      induces systemic antitumor immunity via STING and Batf3-dependent dendritic
      cells.
AB  - Advanced cancers remain a therapeutic challenge despite recent progress in
      targeted therapy and immunotherapy. Novel approaches are needed to alter the
      tumor immunosuppressive microenvironment and to facilitate the recognition of
      tumor antigens that leads to antitumor immunity. Poxviruses, such as modified
      vaccinia virus Ankara (MVA), have potential as immunotherapeutic agents. We show
      that infection of conventional dendritic cells (DCs) with heat- or ultraviolet
      inactivated MVA leads to higher levels of interferon induction than MVA alone
      through the cGAS (cyclic guanosine monophosphate-adenosine monophosphate
      synthase)-STING cytosolic DNA-sensing pathway. Intratumoral injection of
      inactivated MVA (iMVA) was effective and generated adaptive antitumor immunity in
      murine melanoma and colon cancer models. iMVA-induced antitumor therapy was less
      effective in STING- or Batf3-deficient mice than in wild-type mice, indicating
      that both cytosolic DNA sensing and Batf3-dependent CD103+/CD8alpha+ DCs are
      essential for iMVA immunotherapy. The combination of intratumoral delivery of
      iMVA and systemic delivery of immune checkpoint blockade generated synergistic
      antitumor effects in bilateral tumor implantation models as well as in a
      unilateral large established tumor model. Our results suggest that inactivated
      vaccinia virus could be used as an immunotherapeutic agent for human cancers.

PMID- 28763796
TI  - The metabolic regulator mTORC1 controls terminal myeloid differentiation.
AB  - Monocytes are derived from hematopoietic stem cells through a series of
      intermediate progenitor stages, but the factors that regulate this process are
      incompletely defined. Using a Ccr2/Cx3cr1 dual-reporter system to model murine
      monocyte ontogeny, we conducted a small-molecule screen that identified an
      essential role of mechanistic target of rapamycin complex 1 (mTORC1) in the
      development of monocytes and other myeloid cells. Confirmatory studies using mice
      with inducible deletion of the mTORC1 component Raptor demonstrated absence of
      mature circulating monocytes, as well as disruption in neutrophil and dendritic
      cell development, reflecting arrest of terminal differentiation at the
      granulocyte-monocyte progenitor stage. Conversely, excess activation of mTORC1
      through deletion of the mTORC1 inhibitor tuberous sclerosis complex 2 promoted
      spontaneous myeloid cell development and maturation. Inhibitor studies and stage
      specific expression profiling identified failure to down-regulate the
      transcription factor Myc by the mTORC1 target ribosomal S6 kinase 1 (S6K1) as the
      mechanistic basis for disrupted myelopoiesis. Together, these findings define the
      mTORC1-S6K1-Myc pathway as a key checkpoint in terminal myeloid development.

PMID- 28763803
TI  - Executive Functions Impact the Relation Between Respiratory Sinus Arrhythmia and
      Frequency of Stuttering in Young Children Who Do and Do Not Stutter.
AB  - Purpose: This study sought to determine whether respiratory sinus arrhythmia
      (RSA) and executive functions are associated with stuttered speech disfluencies
      of young children who do (CWS) and do not stutter (CWNS). Method: Thirty-six
      young CWS and 36 CWNS were exposed to neutral, negative, and positive emotion
      inducing video clips, followed by their participation in speaking tasks. During
      the neutral video, we measured baseline RSA, a physiological index of emotion
      regulation, and during video viewing and speaking, we measured RSA change from
      baseline, a physiological index of regulatory responses during challenge.
      Participants' caregivers completed the Children's Behavior Questionnaire from
      which a composite score of the inhibitory control and attentional focusing
      subscales served to index executive functioning. Results: For both CWS and CWNS,
      greater decrease of RSA during both video viewing and speaking was associated
      with more stuttering. During speaking, CWS with lower executive functioning
      exhibited a negative association between RSA change and stuttering; conversely,
      CWNS with higher executive functioning exhibited a negative association between
      RSA change and stuttering. Conclusion: Findings suggest that decreased RSA during
      video viewing and speaking is associated with increased stuttering and young CWS
      differ from CWNS in terms of how their executive functions moderate the relation
      between RSA change and stuttered disfluencies.

PMID- 28763804
TI  - Neurogenic Orofacial Weakness and Speech in Adults With Dysarthria.
AB  - Purpose: This study compared orofacial strength between adults with dysarthria
      and neurologically normal (NN) matched controls. In addition, orofacial muscle
      weakness was examined for potential relationships to speech impairments in adults
      with dysarthria. Method: Matched groups of 55 adults with dysarthria and 55 NN
      adults generated maximum pressure (Pmax) against an air-filled bulb during
      lingual elevation, protrusion and lateralization, and buccodental and labial
      compressions. These orofacial strength measures were compared with speech
      intelligibility, perceptual ratings of speech, articulation rate, and fast
      syllable-repetition rate. Results: The dysarthria group demonstrated
      significantly lower orofacial strength than the NN group on all tasks. Lingual
      strength correlated moderately and buccal strength correlated weakly with most
      ratings of speech deficits. Speech intelligibility was not sensitive to
      dysarthria severity. Individuals with severely reduced anterior lingual elevation
      Pmax (< 18 kPa) had normal to profoundly impaired sentence intelligibility (99%
      6%) and moderately to severely impaired speech (26%-94% articulatory imprecision;
      33%-94% overall severity). Conclusions: Results support the presence of orofacial
      muscle weakness in adults with dysarthrias of varying etiologies but reinforce
      tenuous links between orofacial strength and speech production disorders. By
      examining individual data, preliminary evidence emerges to suggest that speech,
      but not necessarily intelligibility, is likely to be impaired when lingual
      weakness is severe.

PMID- 28763806
TI  - Noise Equally Degrades Central Auditory Processing in 2- and 4-Year-Old Children.
AB  - Purpose: The aim of this study was to investigate developmental and noise-induced
      changes in central auditory processing indexed by event-related potentials in
      typically developing children. Method: P1, N2, and N4 responses as well as
      mismatch negativities (MMNs) were recorded for standard syllables and consonants,
      frequency, intensity, vowel, and vowel duration changes in silent and noisy
      conditions in the same 14 children at the ages of 2 and 4 years. Results: The P1
      and N2 latencies decreased and the N2, N4, and MMN amplitudes increased with
      development of the children. The amplitude changes were strongest at frontal
      electrodes. At both ages, background noise decreased the P1 amplitude, increased
      the N2 amplitude, and shortened the N4 latency. The noise-induced amplitude
      changes of P1, N2, and N4 were strongest frontally. Furthermore, background noise
      degraded the MMN. At both ages, MMN was significantly elicited only by the
      consonant change, and at the age of 4 years, also by the vowel duration change
      during noise. Conclusions: Developmental changes indexing maturation of central
      auditory processing were found from every response studied. Noise degraded sound
      encoding and echoic memory and impaired auditory discrimination at both ages. The
      older children were as vulnerable to the impact of noise as the younger children.
      Supplemental materials: https://doi.org/10.23641/asha.5233939.

PMID- 28763807
TI  - [Therapy of Advanced Basal Cell Carcinoma by Hedgehog Inhibition].

PMID- 28763808
TI  - Endocuff-assisted colonoscopy is associated with a lower adenoma miss rate: a
      multicenter randomized tandem study.
AB  - Background and study aims The Endocuff (ARC Medical Design, Leeds, UK) is a
      device that, when mounted on the tip of an endoscope, may assist with inspection
      of a greater surface of the colonic mucosa by pulling backwards, flattening, and
      stretching the colonic folds as the endoscope is gradually withdrawn. We aimed to
      compare the adenoma miss rates of Endocuff-assisted colonoscopy with those of
      conventional colonoscopy. Patients and methods The included patients underwent
      same-day, back-to-back, (Endocuff-assisted colonoscopy as the index procedure
      followed by conventional colonoscopy or vice versa, randomly assigned 1:1)
      colonoscopies, performed by six endoscopists with documented adenoma detection
      rates > 35 %, in four tertiary endoscopy facilities. Results We randomized 200
      patients (mean age 61.2 years [standard deviation 9.8]; 86.5 % colorectal cancer
      screening surveillance cases). Overall, there were seven incomplete examinations
      using Endocuff and one with conventional colonoscopy (P = 0.03). Times for
      endoscope insertion (5.0 minutes [0.8 - 21.0] vs. 5.0 minutes [1.0 - 16.0]; P =
      0.49) and withdrawal (6.0 minutes [3.2 - 29.0] vs. 6.0 minutes [3.1 - 17.0]; P =
      0.06) were similar for Endocuff-assisted and conventional colonoscopy. We
      detected one cancer and 195 adenomas; 84 in the proximal colon. Endocuff-assisted
      colonoscopy showed significantly lower overall and proximal colon adenoma miss
      rates compared with conventional colonoscopy (14.7 % [8.0 % - 21.0 %] vs. 38.4 %
      [28.1 % - 48.6 %] and 10.4 % [1.8 % - 19.1 %] vs. 38.9 % [23.0 % - 54.8 %],
      respectively). No difference between the two arms was shown regarding advanced
      adenoma miss rates, either overall or in the proximal colon. There were no
      serious adverse events related to the procedures. Conclusions In comparison with
      conventional colonoscopy, Endocuff-assisted colonoscopy has a significantly lower
      adenoma miss rate when performed by high-detector endoscopists. However, the
      incomplete colonoscopy rate with Endocuff is higher.ClinicalTrials.gov
      Identifier: NCT02340065.

PMID- 28763805
TI  - beta1-Integrin Deletion From the Lens Activates Cellular Stress Responses Leading
      to Apoptosis and Fibrosis.
AB  - Purpose: Previous research showed that the absence of beta1-integrin from the
      mouse lens after embryonic day (E) 13.5 (beta1MLR10) leads to the perinatal
      apoptosis of lens epithelial cells (LECs) resulting in severe microphthalmia.
      This study focuses on elucidating the molecular connections between beta1
      integrin deletion and this phenotype. Methods: RNA sequencing was performed to
      identify differentially regulated genes (DRGs) in beta1MLR10 lenses at E15.5. By
      using bioinformatics analysis and literature searching, Egr1 (early growth
      response 1) was selected for further study. The activation status of certain
      signaling pathways (focal adhesion kinase [FAK]/Erk, TGF-beta, and Akt signaling)
      was studied via Western blot and immunohistochemistry. Mice lacking both beta1
      integrin and Egr1 genes from the lenses were created (beta1MLR10/Egr1-/-) to
      study their relationship. Results: RNA sequencing identified 120 DRGs that
      include candidates involved in the cellular stress response, fibrosis, and/or
      apoptosis. Egr1 was investigated in detail, as it mediates cellular stress
      responses in various cell types, and is recognized as an upstream regulator of
      numerous other beta1MLR10 lens DRGs. In beta1MLR10 mice, Egr1 levels are elevated
      shortly after beta1-integrin loss from the lens. Further, pErk1/2 and pAkt are
      elevated in beta1MLR10 LECs, thus providing the potential signaling mechanism
      that causes Egr1 upregulation in the mutant. Indeed, deletion of Egr1 from
      beta1MLR10 lenses partially rescues the microphthalmia phenotype. Conclusions:
      beta1-integrin regulates the appropriate levels of Erk1/2 and Akt phosphorylation
      in LECs, whereas its deficiency results in the overexpression of Egr1,
      culminating in reduced cell survival. These findings provide insight into the
      molecular mechanism underlying the microphthalmia observed in beta1MLR10 mice.

PMID- 28763809
TI  - [Correction: Innovative Ultrasound: Contrast-Enhanced Ultrasound of the Kidneys].

PMID- 28763810
TI  - [Correction: Bacteriuria after Radical Prostatectomy: Importance of Bacterial
      Count].

PMID- 28763811
TI  - [Ribeiro-Technique in Gigantomastia - Review of 294 Reduction Mammaplasties in 8
      Years].
AB  - INTRODUCTION: Reduction mammaplasty in patients with gigantomastia is challenging
      even to very experienced plastic surgeons. Extremely elongated pedicles impair
      the vascular supply of the nipple-areola complex. Breast shaping and effective
      reduction are difficult due to the severely stretched skin envelope. The Ribeiro
      technique is the standard technique for reduction mammaplasty in our clinic. The
      aim of this study is to review our approach in patients with gigantomastia in
      comparison to the current literature. PATIENTS UND METHODS: From 01/2009 to
      12/2016, we performed 1247 reduction mammaplasties in 760 patients. In 294
      reduction mammoplasties (23.6 %), resection weight was more than 1000 g per
      breast corresponding to the definition of gigantomastia. The Ribeiro technique
      with a superomedial pedicle and inferior dermoglandular flap for autologous
      augmentation of the upper pole was implemented as standard procedure. In cases
      with a sternal notch-nipple distance > 40 cm, free nipple grafting was performed.
      The outcome parameters complication rate, patient satisfaction with the aesthetic
      result, nipple sensitivity and surgical revision rate were obtained and
      retrospectively analysed. RESULTS: In 174 patients, 294 reduction mammaplasties
      were performed with a resection weight of more than 1000 g per breast. Average
      resection weight was 1389.6 g (range, 1000-4580 g). Average age was 43.5 years
      (range, 18-76 years), average body mass index (BMI) was 29.2 kg/m2 (range, 19-40
      kg/m2), average sternal notch-nipple distance was 34.8 cm (range, 27-52 cm),
      average operation time was 117 minutes (range, 72-213 minutes). A free nipple
      graft was necessary in 30 breasts. Overall complication rate was 7.8 %; secondary
      surgical revision rate was 16 %. 93 % of the patients were "very satisfied" and
      "satisfied" with the aesthetic result. Nipple sensitivity was rated "very good"
      and "good" in 88 %. CONCLUSION: The Ribeiro technique is a well established,
      versatile standard technique for reduction mammaplasty, which helps to create
      high-quality reproducible results with longterm formstable shape. In
      gigantomastia, this procedure is also very effective to achieve volume reduction
      and aesthetically pleasing results with a low complication rate.

PMID- 28763812
TI  - [Mastopexy in Massive Weight Loss Patients - Extended Ribeiro Technique and Usage
      of the Lateral Intercostal Artery Perforator Flap (LICAP Flap) for
      Autoaugmentation].
AB  - INTRODUCTION: Mastopexy in massive weight loss patients is challenging. The
      breast mound is often unstable and deflated, with a loose inelastic skin
      envelope. It has become apparent that mammaplasty techniques in these cases
      should rely more on glandular recontouring rather than on the skin envelope for
      shaping. Published methods include plication, suspension and autoaugmentation.
      The residual local tissue (glandular breast tissue, fat tissue, dermoglandular
      fat flap) is utilised to its full extent in order to reshape a form-stable breast
      with full upper pole projection. The evolution of a technique is presented.
      PATIENTS AND METHODS: In this study we retrospectively analysed 68 massive weight
      loss patients who underwent an extended Ribeiro technique with a superomedial
      pedicle mastopexy and suspension by an inferior dermoglandular flap. The current
      procedure involves incorporating the lateral intercostal artery perforator flap
      (LICAP flap) and medial breast pillar additionally to the inferior dermoglandular
      Ribeiro flap. This essentially autoaugments the upper pole by creating an
      "autoprosthesis", narrows the widened breast, and redefines the inframammary
      fold. The outcome parameters complication rate, patient satisfaction with the
      aesthetic result, nipple sensibility and surgical revision rate were obtained.
      RESULTS: From 01/2011 to 12/2016, we performed 136 autoaugmentation mastopexies.
      The average age was 41.2 years, average body mass index (BMI) was 27,1 kg/m2,
      average weight loss was 54.3 kg, average sternal notch-NAC distance was 32.3 cm,
      average operation time was 109 minutes. In 12 breasts, a free-nipple graft was
      necessary. The complication rate was 5.1 %, surgical revision rate was 17.6 %. 95
      % of the patients were "very satisfied" or "satisfied" with the aesthetic result.
      Nipple sensibility was rated as "very good" or "good" by 85 % of patients.
      CONCLUSION: Modification of the Ribeiro technique by using the medial and lateral
      breast pillar (LICAP flap) allows autoaugmentation of the upper pole. Parenchymal
      shaping through plication and suspension of the breast mound should improve
      breast shape over time, with the aim of reducing the incidence of recurrent
      ptosis. The presented technique is a reproducible and reliable method with a low
      complication rate.

PMID- 28763813
TI  - [The Body Dysmorphic Disorder in Plastic Surgery - A Systematic Review of
      Screening Methods].
AB  - BACKGROUND: The body dysmorphic disorder (BDD) is considered to be a sub-form of
      somatoform disorders. BDD can express itself in a delirious experience, an
      excessive evaluation and employment of the external appearance, in particular the
      face. Preliminary results suggest that individuals with BDD do not benefit from
      plastic surgery, so that aesthetic surgery often results in aggravation of their
      symptoms. Thus, the identification of signs for a BDD is crucial, whether a
      patient should be operated plastically-aesthetically. This overview explains the
      often difficult diagnostics of the BDD by summarizing the current literature on
      its screening. STUDY DESIGN: Systematic overview METHODS: An electronic search
      was conducted in the German and English-language literature in order to identify
      all screening instruments for the BDD. The specific development and validation
      processes are assessed whether the screening instruments have a positive
      predictive value for the BDD. RESULTS: Six different screening instruments were
      identified for the BDD. Only two of these were evaluated in a cosmetic setting:
      the "Body Dysmorphic Disorder Questionnaire Dermatology Version" (BDDQ-DV) and
      the "Dysmorphic Concern Questionnaire" (DCQ). The influence on the subjective
      results after a plastic-aesthetic procedure was measured only for the DCQ.
      CONCLUSION: The limited availability of validated screening instruments for BDD
      in plastic surgery is markedly in contrast to the supposedly high prevalence of
      the disease of 2.4 %. Among the currently used screening tools, the BDDQ-DV and
      the DCQ appear to be most suitable. Further research efforts are needed to
      establish better screening methods for the BDD in the plastic surgical patient
      population and to examine the effects of BDD on treatment results.

PMID- 28763814
TI  - Three modalities on common bile duct exploration.
AB  - Background Choledocholithiasis can be managed by transcystic (TC) and transduct
      (TD) stone extraction or using cholangioscopy through the left hepatic duct
      orifice (LHD). Objective The aim of this study is to evaluate the safety and
      effectiveness of common bile duct exploration through the TC approach, TD
      approach, and LHD approach for choledocholithiasis, with a specific emphasis on
      the TC and LHD approaches versus the TD approach. Methods Between January 2011
      and June 2014, a total of 172 choledocholithiasis patients accompanied by
      cholecystitis and/or left intrahepatic gallstones were scheduled for laparoscopic
      or open common bile duct (CBD) exploration using cholangioscopy through the CBD
      (TD group: n = 72), cystic duct (TC group: n = 63), or LHD orifice (LHD group: n
      = 37). T-tube insertion was performed in selected patients. Patients were
      regularly followed up at bimonthly intervals or more frequently in presence of
      any symptom. Primary outcomes measures included overall operative time, length of
      hospital stay, and postoperative bile leaks. Results Successful bile duct
      clearance was 100 % in the TD group, 93.6 % in the TC group, and 90.9 % in the
      LHD group. Sixteen cases in the TD group had T-tube placement in contrast to no
      cases in the TC and LHD groups. There were more bile leaks after TD stone
      extraction (12.5 %) than TC (3.2 %) and LHD stone extraction (0 %), which
      prolonged hospitalization in the TD group more than in the TC and LHD groups. For
      choledocholithiasis patients accompanied by cholecystitis, 2 groups (TC and TD
      groups) were comparable in operative time. However, for choledocholithiasis
      patients accompanied by left intrahepatic gallstones, the LHD group had a
      significantly shorter operative time than the TD group (121.1 +/- 16.9 minutes
      vs. 149.3 +/- 42.8 minutes, p < 0.05). Conclusion The TD group had a higher stone
      clearance rate but was associated with a higher risk of bile leaks. TC and LHD
      stone extraction, which seems to be the more effective approach with lower
      complication rates, is an accessible technique that simplifies the operation
      procedure by avoiding choledochotomy and subsequent T-tube insertion.

PMID- 28763815
TI  - [1+1+1 = Multimorbidity is More than the Addition of Monopathologies].

PMID- 28763816
TI  - [Drug-Coated Balloons and Stents for the Treatment of Femoro-Popliteal Lesions].

PMID- 28763817
TI  - [Current Diagnostics and Treatment of Thyroid Nodules].

PMID- 28763819
TI  - [Diagnosis and Treatment of Echinococcal Diseases].

PMID- 28763818
TI  - [Testosterone deficiency and dementia].

PMID- 28763820
TI  - [Tachycardic Arrhythmias in the Emergency Room - State of the Art].

PMID- 28763821
TI  - [ESC Guidelines 2016 - Heart Failure].

PMID- 28763822
TI  - [Arterial Hypertension - Update 2017].

PMID- 28763823
TI  - [ANCA-associated vasculitides, an update 2017].

PMID- 28763824
TI  - [Endoscopic Therapy of Gastrointestinal Neoplasia].

PMID- 28763825
TI  - [Representation of Internal Medicine in G-DRG System - Analysis of Reasons for
      Prolonged Length of Stay].
AB  - Background There is an ongoing discussion within the German Society of Internal
      Medicine (DGIM) and the Professional Association of German Internists (BDI) about
      the appropriate depiction and remuneration of internal medicine in the G-DRG.
      Method Therefore, cases with a significantly prolonged length of stay were
      analyzed in a multicenter study. 124 cases from 6 hospitals were collected for
      evaluation. Results The results show that the observed prolongation of
      hospitalization was mainly due to medical reasons. Discussion Thus, patients with
      unclear symptoms and consequently need for a thorough workup could not be
      identified to cause longer inpatient stay. Instead, treatment complications and
      comorbidities led to extended hospitalization. The results also reveal prolonged
      hospitalization as a consequence of unsettled or delayed postdischarge care e. g.
      in rehabilitation facilities.

PMID- 28763826
TI  - [25-Year-Old Male with Fatigue, Shortness of Breath and Abdominal Distension].

PMID- 28763827
TI  - [Management of a Port Catheter-Related Superior Vena Cava Thrombosis in the
      Setting of Active Crohn's Disease: A Case Report].
AB  - History and clinical findings A 56 year-old woman was admitted to our hospital
      for treatment of a severe exacerbation of Crohn's disease. During the stay a port
      catheter was implanted, safeguarding nutrition. A few days later the patient
      developed symptoms of a severe superior vena cava (SVC) syndrome with dyspnea,
      cyanosis, headaches and swelling of face and upper extremities. Examination A CT
      scan showed port catheter-associated SVC thrombosis with complete occlusion of
      the SVC. Diagnosis There was a coexistence of a port catheter-associated SVC
      thrombosis with complete occlusion of the SVC and a severe exacerbation of
      Crohn's disease with haematochezia. Therapy and clinical course Local prolonged
      thrombolysis through the port catheter analogous to the regimen used in the 2012
      CaVenT Study was started. Subsequently, symptoms of SVC obstruction as well as
      thrombus extent improved markedly, with only minor increase in gastrointestinal
      bleeding. Conclusion Local thrombolysis appears to be a safe and effective
      therapy for port catheter-associated thrombosis that may be considered in the
      setting of increased risk of hemorrhage.

PMID- 28763828
TI  - Muscle-bone interactions: movement in the field of mechano-humoral coupling of
      muscle and bone.
AB  - Cyclical, mechanical loading of bone by skeletal muscle is widely recognized as a
      critical determinant of bone structure and mass. A growing body of evidence
      indicates that substances released from skeletal muscle into the bloodstream also
      regulate bone mass and metabolism. In this commentary, we discuss the status of
      research in the area of humoral regulation of bone mass by the skeletal muscle
      secretome, with an emphasis on the roles of myostatin, irisin, interleukin-6, and
      exosomes. The interplay between muscle, bone, and other modulators of bone mass,
      including circadian rhythm and sympathetic tone, is also discussed.

PMID- 28763829
TI  - F-group bZIPs in barley-a role in Zn deficiency.
AB  - Zinc (Zn) deficiency negatively impacts the development and health of plants and
      affects crop yield. When experiencing low Zn, plants undergo an adaptive response
      to maintain Zn homeostasis. We provide further evidence for the role of F-group
      transcription factors, AtbZIP19 and AtbZIP23, in responding to Zn deficiency in
      Arabidopsis and demonstrate the sensitivity and specificity of this response.
      Despite their economic importance, the role of F-group bZIPs in cereal crops is
      largely unknown. Here, we provide new insights by functionally characterizing
      these in barley (Hordeum vulgare), demonstrating an expanded number of F-group
      bZIPs (seven) compared to Arabidopsis. The F-group barley bZIPs, HvbZIP56 and
      HvbZIP62, partially rescue the Zn-dependent growth phenotype and ZIP-transporter
      gene regulation of an Arabidopsis bzip19-4 bzip23-2 mutant. This supports a
      conserved mechanism of action in adapting to Zn deficiency. HvbZIP56 localizes to
      the cytoplasm and nucleus when expressed in Arabidopsis and tobacco. Promoter
      analysis demonstrates that the barley ZIP transporters that are upregulated under
      Zn deficiency contain cis Zn-deficiency response elements (ZDREs). ZDREs are also
      found in particular barley bZIP promoters. This study represents a significant
      step forward in understanding the mechanisms controlling Zn responses in cereal
      crops, and will aid in developing strategies for crop improvement.

PMID- 28763830
TI  - Apical cytoskeletons and junctional complexes as a combined system in epithelial
      cell sheets.
AB  - Epithelial cell sheet formation is central to many aspects of vertebrate
      development and function. For example, it is a major principle of differentiation
      in embryogenesis and regeneration, enables the compartmentalization of tissues,
      and is the basis for the maintenance of homeostasis throughout the body. A key
      characteristic of biologically functional epithelial cell sheets is a clear
      difference between the top and bottom sides owing to the apicobasal polarity of
      the cells in the sheet, as seen in the simple polar epithelia. Epithelial cell
      sheets are formed by cell-cell adhesion conferred by junctional complexes, in
      particular via tight junctions (TJs), which thus create a paracellular barrier.
      This review focuses on the apical side of the sheet, which serves as the front
      line. The apical membranes and TJs of the various tissues have specific
      characteristics that enable them to function and adapt to their biological
      context: each system must be robust, but also dynamic and flexible to maintain
      homeostasis. Here, we describe various apical cytoskeletal structures that are
      critical to the integrity of epithelial cell sheets. We also discuss the
      association of apical cytoskeletal networks with TJs, which thus forms a combined
      system, tentatively termed the TJ-apical complex.

PMID- 28763831
TI  - Preparation-related structural diversity and medical potential in the treatment
      of diabetes mellitus with ginseng pectins.
AB  - Pectins isolated from Panax ginseng C.A. Meyer are potential therapeutic agents
      for the treatment of diabetes mellitus, a global health challenge. Soil-to-bench
      procedures of ginseng pectin preparation significantly affect the polysaccharide
      structures. Various forms of ginseng pectins rich in homogalacturonan,
      rhamnogalacturonan-I, rhamnogalacturonan-II, and arabinogalactan have
      demonstrated independent or collaborative effects on hyperglycemia, oxidative
      stress, immunological dysfunction, and neoplasms. Monosaccharide compositions,
      peptide contents, degrees of esterification and methylation, and inter- and
      intramolecular linkages all influence pectin bioactivity. Understanding the
      preparation-structure and structure-function relationships of ginseng pectins can
      lead to safer and more pertinent treatment of diabetes with efficacy-oriented
      modifications of the pectins. To reach this goal, standardization of preparation
      procedures, understanding of intricate structures, and exploration of complex
      interactions with receptors are crucial steps to take full advantage of the
      medical potential of ginseng pectins.

PMID- 28763832
TI  - Are we overestimating intraocular pressure in overweight patients?

PMID- 28763834
TI  - [Hepatocellular carcinoma: co - evolution of hepatocytes and hepatitis B virus].
AB  - Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular
      carcinoma (HCC). In the process from chronic HBV infection to the development of
      HCC, there is a phenomenon of co-evolution of hepatocytes and HBV. The evolution
      of hepatocytes includes dedifferentiation and reverse evolution, while the
      evolution of HBV is mainly "telemorphosis" . Since HBV evolution occurs earlier
      than the development of HCC, the interaction between them is mainly reflected in
      the promotion of HCC evolution by HBV mutation. This article briefly summarizes
      the novel theory termed as cancer evolution and development and elucidates the
      molecular mechanism of HCC caused by HBV from the perspective of evolution.

PMID- 28763835
TI  - [Molecular markers for the monitoring of malignant transformation of hepatocytes
      and early diagnosis of liver cancer].
AB  - The monitoring of malignant transformation of hepatocytes or early diagnosis of
      primary hepatocellular carcinoma (PHC) remains a challenge in the medical world.
      Routine examinations including serum alpha-fetoprotein level and ultrasound
      examination have a limited value in the diagnosis of small hepatocellular
      carcinoma; however, the effective treatment of PHC depends on its early
      diagnosis. In recent years, molecular markers including important signaling
      molecules in PHC-related pathways, carcinoembryonic proteins, and non-coding RNA
      help with the monitoring of malignant transformation of hepatocytes or early
      diagnosis of liver cancer. This article reviews the valuable molecular markers in
      the monitoring of malignant transformation of hepatocytes or early diagnosis of
      liver cancer.

PMID- 28763836
TI  - [Early imaging diagnosis of primary liver cancer].
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the
      liver, and in the process of HCC development, early identification and timely
      treatment can significantly improve patient survival rate. Imaging techniques
      play an important role in the monitoring of chronic liver diseases, evolution of
      cirrhotic nodules, and early diagnosis of HCC. Multi-phase or dynamic contrast
      enhanced computed tomography and magnetic resonance imaging (MRI) reflect the
      changes in blood supply during the evolution of liver cirrhotic nodules.
      Functional MRI can reflect the structure and function of living organisms at the
      molecular level. The application of liver-specific contrast agents can improve
      the detection rate and identification of early-stage HCC. With the development of
      MRI techniques and the accumulation of clinical experience in functional imaging
      will further improve the diagnostic rate of early-stage HCC.

PMID- 28763833
TI  - Deciphering adipose tissue heterogeneity.
AB  - Obesity is an excess accumulation of adipose tissue mass, and, together with its
      sequelae, in particular type II diabetes and metabolic syndrome, obesity presents
      a major health crisis. Although obesity is simply caused by increased adipose
      mass, the heterogeneity of adipose tissue in humans means that the response to
      increased energy balance is highly complex. Individual subjects with similar
      phenotypes may respond very differently to the same treatments; therefore,
      obesity may benefit from a personalized precision medicine approach. The
      variability in the development of obesity is indeed driven by differences in sex,
      genetics, and environment, but also by the various types of adipose tissue as
      well as the different cell types that compose it. By describing the distinct cell
      populations that reside in different fat depots, we can interpret the complex
      effect of these various players in the maintenance of whole-body energy
      homeostasis. To further understand adipose tissue, adipogenic differentiation and
      the transcriptional program of lipid accumulation must be investigated. As the
      cell- and depot-specific functions are described, they can be placed in the
      context of energy excess to understand how the heterogeneity of adipose tissue
      shapes individual metabolic status and condition.

PMID- 28763837
TI  - [The treatment of early-stage liver cancer].
AB  - Although the diagnostic rate of early-stage liver cancer is low, only these
      patients have a chance of radical treatment, and thus related treatment
      modalities deserve attention. Surgical resection is the preferred choice for the
      treatment of early-stage liver cancer. For patients with high selectivity, local
      treatment including radiofrequency ablation can achieve satisfactory outcomes.
      Liver transplantation is the preferred choice for patients with decompensated
      liver cirrhosis. Early-stage liver cancer has a high postoperative recurrence
      rate, and the research and development of postoperative adjuvant therapy should
      be taken seriously.

PMID- 28763838
TI  - [Modern knowledge and development trend of intrahepatic cholangiocellular
      carcinoma].
AB  - Although intrahepatic cholangiocellular carcinoma (ICC) has a relatively low
      incidence rate, it ranks the second in the most common primary malignant liver
      tumors, with hepatocellular carcinoma ranking the first. Meanwhile, its incidence
      and mortality rates tend to increase significantly in the past decades. On the
      one hand, due to a lack of characteristic clinical symptoms, specific tumor
      markers, and imaging findings, early diagnosis of ICC is extremely difficult; on
      the other hand, ICC has highly malignant biological behaviors and early
      extrahepatic metastasis, so patients often experience early recurrence even if
      surgical resection is performed, which leads to the poor prognosis of such
      patients. Unfortunately, since ICC has a low incidence rate and relatively few
      patients, it is not taken seriously in clinical practice. Since there is a lack
      of clinical data, specimens, and in-depth studies on ICC, its pathogenesis
      remains unclear. This article discusses recent advances in ICC, including risk
      factors, molecular mechanism, new diagnostic markers, and therapies (including
      molecular targeted drugs).

PMID- 28763839
TI  - [Expression of ATAD2 in different liver lesions and its clinical significance].
AB  - Objective: To examine the expression of ATAD2 in different liver lesions and its
      clinical significance. Methods: ATAD2 expression in 60 hepatocellular carcinoma
      (HCC) surgical specimens (49 of which have concurrent liver cirrhosis), 43 HCC
      biopsy specimens, 2 high-grade liver dysplastic nodule specimens, 3 low-grade
      liver dysplastic nodule specimens, 50 liver cirrhosis tissue samples, and 20
      normal liver tissue samples were measured using immunohistochemistry. The F-test,
      q-test, t-test, and chi-square test were used for statistical analysis of data.
      Results: ATAD2 was expressed in 56 HCC surgical specimens (93.33%), 35 HCC biopsy
      specimens (81.40%), and 2 high-grade liver dysplastic nodule specimens (2/2), but
      not in the low-grade liver dysplastic nodule, liver cirrhosis tissue, and normal
      liver tissue samples. The mean expression of ATAD2 was significantly higher in
      HCC tissues than in high-grade and low-grade liver dysplastic nodule tissues,
      liver cirrhosis tissue, and normal liver tissue (F = 22.96, q = 3.138, 3.972,
      12.272, and 9.101, respectively, all P < 0.01). There were no significant
      differences in the mean expression and positive expression rate of ATAD2 between
      HCC surgical and biopsy specimens (t = 1.40, P > 0.05; chi2 = 3.47, P >0.05). Of
      the 35 HCC biopsy specimens that expressed ATAD2, the mean ATAD2 expression was
      >=1% in 35 specimens (100%), >=3% in 27 specimens (77.14%), and >=5 % in 23
      specimens (65.71%). In addition, among the pathological grade I-II HCC biopsy
      specimens, the mean ATAD2 expression was >=1% in 28 specimens (100%), >=3% in 22
      specimens (62.86%), and >=5% in 19 specimens (54.29%). Moreover, ATAD2 expression
      in HCC was associated with serum alpha-fetoprotein level, presence of hepatitis B
      virus surface antigen (HBsAg), and presence of concurrent liver cirrhosis (t =
      2.09, 2.30, and 2.18, respectively, all P < 0.05). Conclusion: ATAD2 may play an
      important role in HCC tumorigenesis, and may be involved in malignant
      transformation of cells. ATAD2 expression can be a valuable marker for
      differentiating the nature of lesions in liver biopsy tissues during clinical
      practice.

PMID- 28763840
TI  - [Efficacy of microwave ablation in treatment of hepatocellular carcinoma within
      the Milan criteria: a report of 696 cases].
AB  - Objective: To investigate the efficacy of microwave ablation in the treatment of
      hepatocellular carcinoma (HCC) within the Milan criteria and to investigate the
      differences in clinical efficacy of microwave ablation in tumors with different
      sizes. Methods: A retrospective analysis was performed on the clinical data of
      the patients with HCC within the Milan criteria who received microwave ablation
      in our hospital from January 2011 to January 2013. The complete ablation rate,
      incidence rate of major complications, recurrence rate, and overall survival rate
      were analyzed and the treatment outcomes were compared between two groups with
      different tumors sizes. The patients were followed up for 3.4-61.8 months. The
      Kaplan-Meier method was used to calculate overall survival rate, local recurrence
      rate, and distant recurrence rate. Comparison of rates between groups was made by
      the chi-square test and comparison of survival rates between groups was made by
      the log-rank test. Results: A total of 696 patients with HCC within the Milan
      criteria involving 801 tumors were included in this study. The complete ablation
      rate was 93.8% (653/696) and the incidence rate of major complications was 1.7%
      (12/696). The median survival time was 59.6 months and the 1-, 2-, and 3-year
      overall survival rates were 94.8%, 82.2%, and 71.7%, respectively. The local
      recurrence rate was 13.4% (93/696) and the rate of intrahepatic distant
      metastasis was 40.1% (279/696). The overall intrahepatic recurrence rate was
      48.1% (335/696), and the 1-, 2-, and 3-year recurrence rates were 22.9%, 38.4%,
      and 46.8%, respectively. There were no significant differences in complete
      ablation rate, incidence rate of major complications, and overall survival rate
      between the two groups with different tumor sizes (diameters<=3 cm and 3-5 cm) (P
      = 0.12; P = 0.61; P = 0.61). Conclusion: Microwave ablation is a safe and
      effective treatment modality for HCC within the Milan criteria. And there are no
      significant differences in safety, effectiveness, and long-term efficacy of
      microwave ablation between the two groups with different tumor sizes (diameters
      <=3 cm and 3-5 cm). However, if the operator's experience is not rich and cannot
      accurately use conformal ablation and make an individualized treatment, the
      tumors with a diameter of 3-5 cm should be carefully treated using microwave
      ablation to avoid residual tumor after treatment.

PMID- 28763841
TI  - [Copy number aberrations of genes related to extrohepatic metastasis-free
      survival after operation for hepatocellular carcinoma].
AB  - Objective: To investigate the molecular markers of copy number aberrations (CNAs)
      of genes related to extrohepatic metastasis-free survival after the operation for
      hepatocellular carcinoma (HCC). Methods: The CNA status of 20 candidate genes in
      66 HCC samples was detected by microarray comparative genomic hybridization. The
      associations between gene CNAs and extrohepatic metastasis-free survival were
      evaluated using the Cox regression model, Log-rank test, and Kaplan-Meier
      survival analysis. Results: Multivariate Cox analysis revealed that the
      independent risk factors for metastasis-free survival were MDM4 gain (hazard
      ratio [HR] = 2.74, 95% confidence interval [CI] = 1.18-6.37, P < 0.05), APC loss
      (HR = 8.43, 95% CI = 2.48-28.66, P < 0.01), and BCL2L1 gain (HR = 3.45, 95% CI =
      1.13-10.52, P < 0.05) and the independent protective factor was FBXW7 loss (HR =
      0.32, 95% CI = 0.12-0.89, P < 0.05). By stepwise Cox regression analysis, three
      CNAs related to metastasis-free survival were screened out: MDM4 gain (HR = 2.71,
      95% CI = 1.11-6.64, P < 0.05), APC loss (HR = 7.19, 95% CI = 1.88-27.60, P <
      0.005), and FBXW7 loss (HR = 0.16, 95% CI = 0.05-0.46, P < 0.01). There were
      significant differences in metastasis-free survival rate between the HCC patients
      with FBXW7 loss and without MDM4 gain or APC loss, those with MDM4 gain and/or
      APC loss and without FBXW7 loss, and those with other CNA combinations (log-rank
      test, P < 0.01). Conclusion: MDM4 gain, APC loss, and FBXW7 loss are the
      independent prognostic factors for extrohepatic metastasis-free survival after
      the operation for HCC and can be used to predict the risk of extrohepatic
      metastasis after the operation for HCC.

PMID- 28763842
TI  - [Effect of CCR1 gene overexpression on the migration of bone marrow - derived
      mesenchymal stem cells towards hepatocellular carcinoma].
AB  - Objective: To evaluate the effect of human CCR1 (hCCR1) gene overexpression on
      the migration of human bone marrow-derived mesenchymal stem cells (hMSCs) towards
      hepatocellular carcinoma (HCC), and to examine the application prospects of MSCs
      as gene delivery vectors in the treatment of HCC. Methods: The hCCR1 gene was
      subcloned into a lentiviral vector to generate the recombinant plasmid pLV-hCCR1.
      The pLV-hCCR1 plasmid and two other packaging plasmids were co-transfected into
      293T cells using calcium phosphate, and the virus-containing supernatant was
      collected. hMSCs were then infected with the recombinant lentivirus, and the
      expression of hCCR1 mRNA and protein was analyzed by RT-PCR and Western blot,
      respectively. The effect of CCR1 gene overexpression on the in vitro migration of
      hMSCs was examined using the Transwell migration assay. Orthotopic nude mice
      models of HCC were established using the MHCC-97H-GFP cell line, and the mice
      were divided into two groups (n = 8 per group). hMSCs were then intravenously
      injected via the tail vein into the tumor-bearing nude mice to examine the effect
      of hCCR1 overexpression on the in vivo migration of hMSCs towards HCC. Unpaired
      Student's t-test was used for two-group comparisons, and one-way ANOVA was used
      for multi-group comparisons. Results: Restriction enzyme digestion and DNA
      sequencing demonstrated that the recombinant plasmid pLV-hCCR1 was constructed
      successfully. The LV-hCCR1 lentivirus packaged by 293T cells has high infection
      efficiency in hMSCs, and hCCR1 was overexpressed in hMSCs after LV-hCCR1
      infection. Transwell migration assay showed that hCCR1-transfected hMSCs had
      significantly enhanced migration towards HCC cell line-derived condition medium
      (CM) compared with the control RFP-hMSCs [(134.8+/-15.7)/LPF vs (83.5+/
      10.9)/LPF, t = 10.40, P < 0.01]. In vivo migration experiment also demonstrated
      that there was significantly higher number of hCCR1-hMSCs localized within the
      MHCC-97H-GFP xenografts than hMSCs-RFP on day 14 following intravenous injection
      of hMSCs in mice [(86.7+/-14.1)/HPF vs (54.5+/-9.6)/HPF, t = -7.32, P < 0.01].
      Conclusion: Overexpression of CCR1 gene can significantly enhance the migration
      capacity of hMSCs towards HCC cells in vitro and in vivo. This study provides
      evidence for potential clinical application of MSCs as more effective delivery
      vehicles in cancer gene therapy.

PMID- 28763843
TI  - [Diagnostic value of serum cystatin C for acute kidney injury in patients with
      liver cirrhosis].
AB  - Objective: To determine the diagnostic value of serum cystatin C (Cys C) for
      acute kidney injury (AKI) in patients with liver cirrhosis. Methods: Serum Cys C
      levels in 150 liver cirrhosis patients (88 AKI and 62 non-AKI patients) were
      measured by the Particle-Enhanced Nephelometric Immuno-Assay. The accuracy of
      serum Cys C for the diagnosis of AKI in liver cirrhosis was evaluated by the ROC
      curve. Results: Liver cirrhosis patients with AKI had significantly higher serum
      Cys C levels [2.37 (1.75-2.83) mg/L] than those without AKI [0.97 (0.85-1.09)
      g/L] (P <0.001). Serum Cys C level was highest in the acute tubular necrosis
      group [5.41 (2.77-6.19) mg/L], followed by the hepatorenal syndrome group [2.55
      (2.28-3.59) mg/L] and prerenal azotemia group [2.07 (1.70-2.41) mg/L], and the
      serum Cys C level was significantly different between the three groups (P
      <0.001). In addition, patients with AKI were further divided into infection group
      and non-infection group. Serum Cys C level was significantly higher in the
      infection group than in the non-infection group (P <0.05). The area under the ROC
      curve of serum Cys C for the diagnosis of AKI in liver cirrhosis was 0.99 (0.98
      1.00) at a cut-off value of 1.36 mg/L, and the sensitivity and specificity were
      97% and 95%, respectively. Conclusion: Serum Cys C is a good marker for detecting
      AKI in liver cirrhosis, and the different levels of increase in Cys C may be
      useful in differentiating the different types of AKI.

PMID- 28763844
TI  - [Mechanism of action of Yiqi Huoxue Recipe in regulating autophagy and reversing
      liver fibrosis].
AB  - Objective: To investigate the role and mechanism of action of Yiqi Huoxue Recipe
      (YQHXR) in regulating autophagy and reversing liver fibrosis in rats with carbon
      tetrachloride (CCl4)-induced liver fibrosis. Methods: Healthy male Wistar rats
      were intraperitoneally injected with a mixture of CCl4 (30%) and olive oil (70%)
      twice a week for 8 weeks to establish a rat model of liver fibrosis. The rats
      administered normal diet were used as control group. Furthermore, YQHXR or
      Fuzheng Huayu Recipe (FZHYR) was intragastrically administered to the rats. The
      serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) were measured using an automatic biochemical analyzer. Hematoxylin-eosin
      (HE) staining and Masson staining were performed to observe the degree of
      fibrosis in rat liver. The protein expression of alpha-smooth muscle actin (alpha
      SMA) and type I collagen alpha1 chain (Col1A1) in liver tissue was measured by
      immunohistochemistry. Furthermore, the mRNA and protein expression of alpha-SMA,
      Col1A1, autophagy-related protein 7 (Atg7), microtubule-associated protein 1
      light chain 3 (LC3), and ubiquitin-binding protein (SQSTM1/p62) were determined
      using qRT-PCR and Western blotting, respectively. Comparison between multiple
      groups was made by one-way analysis of variance, and comparison between any two
      groups was made using the LSD test. P < 0.05 was considered as statistically
      significant. Results: The YQHXR group and FZHYR group had significantly lower
      serum levels of ALT and AST than the model group (ALT: 66.8+/-10.42 U/L and
      73.2+/-10.33 U/L vs 106.80+/-18.24 U/L, F = 31.672, P < 0.001; AST: 122.6+/-16.65
      U/L and 125.4+/-16.92 U/L vs 278.4+/-66.14 U/L, F = 25.539, P < 0.001). The
      pathological grades of hepatic fibrosis were S5.64+/-0.22, S3.70+/-0.35, and
      S3.90+/-0.34 in the model group, YQHXR group, and FZHYR group, respectively (F =
      362.188, P < 0.001). Compared with the control group, the YQHXR group and FZHYR
      group had significantly reduced mRNA and protein expression of alpha-SMA, Col1A1,
      Atg7, and LC3B and significantly increased expression of p62 (all P < 0.05), and
      the differences were greatest in the YQHXR group. Conclusion: YQHXR and FZHYR can
      prevent or reverse liver fibrosis by regulating hepatocyte autophagy and
      inhibiting hepatic stellate cell activation and collagen deposition.

PMID- 28763846
TI  - [Correlation between viral load and expression of programmed death-1 on the
      surface of T follicular helper cells in patients with chronic hepatitis C].

PMID- 28763845
TI  - [Sivelestat alleviates nonalcoholic steatohepatitis in mice through inhibiting
      activation of Kupffer cells].
AB  - Objective: To investigate the role of neutrophil elastase inhibitor, sivelestat,
      in preventing and treating nonalcoholic steatohepatitis (NASH) and its underling
      mechanisms. Methods: A total of forty 4-week-old male C57BL/6J ApoE-/-mice were
      equally divided into the following four groups: standard chow (SC)+isotonic
      saline; SC+sivelestat; high-fat, high-cholesterol (HFHC) diet+isotonic saline;
      and HFHC+sivelestat. These mice were treated with above methods for 12 weeks.
      Blood and liver tissue samples were collected to measure biochemical parameters,
      hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) activity score
      (inflammation) were evaluated by oil red O staining and HE staining,
      respectively. The mRNA and protein expression levels of hepatic inflammatory
      cytokines, CD68, and F4/80 were determined by quantitative RT-PCR and
      immunohistochemistry, respectively. Comparison of means between the four groups
      was made by one-way analysis of variance, and comparison between any two groups
      was made by the LSD or SNK method (for data with homogeneity of variance) or the
      Tamhane or Dunnett method (for data with heterogeneity of variance). Results:
      Mice fed with an HFHC diet for 12 weeks developed typical pathological features
      of NASH compared with those fed with SC. Compared with mice fed with HFHC diet
      without sivelestat, those treated with HFHC and sivelestat exhibited the
      following features: (1) significantly reduced fast blood glucose, blood
      cholesterol, and hepatic biochemical parameters, as well as increased insulin
      sensitivity; (2) significantly reduced NAFLD activity score (5.71+/-1.11 vs
      3.16+/-1.16, P < 0.05); (3) reduced monocyte chemoattractant protein-1 and tumor
      necrosis factor -alpha; (4) significantly reduced mRNA levels of CD68 and F4/80;
      and (5) reduced expression of CD68 in the liver. Conclusion: Sivelestat
      alleviates the hepatic steatosis and inflammation of NASH in mice by inhibiting
      the activation of Kupffer cells.

PMID- 28763847
TI  - [Clinical features and prognosis of hepatitis E-related liver failure: an
      analysis of 127 cases].

PMID- 28763848
TI  - [Clinical significance of peripheral cortisol level in patients with hepatitis B
      virus-related acute-on-chronic liver failure].

PMID- 28763849
TI  - [Changes in the expression of high-mobility group box 1 and hepatocyte nuclear
      factor 1alpha during the formation of liver fibrosis and their correlation with
      liver fibrosis score: an experimental study].

PMID- 28763850
TI  - [Research advances in epithelial - mesenchymal transition in hepatocellular
      carcinoma].
AB  - Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells
      lose their own features and become mesenchymal cells, and more and more studies
      have shown that EMT plays an important role in the invasion and metastasis of
      hepatocellular carcinoma (HCC). This article reviews the signaling pathways
      involved in the progression of HCC and molecules involved in the regulation of
      EMT, in order to provide a new direction for the treatment of HCC.

PMID- 28763851
TI  - [Influence of long non - coding RNA on liver diseases and related mechanisms].
AB  - Non-coding RNAs include microRNAs and long non-coding RNAs (lncRNAs) and are a
      group of RNAs in the product of genome transcription which do not encode
      proteins. In recent years, with the development of screening technology, more and
      more lncRNAs have been identified. Related studies show that these lncRNAs play
      an important role in the development and progression of liver diseases. This
      article reviews the research advances in the influence of lncRNAs on liver
      diseases and related mechanisms.

PMID- 28763852
TI  - [Research advances in risk factors for alcoholic liver disease].
AB  - Only a small number of people may develop severe alcoholic liver disease after
      continuous or excessive drinking, which is different from the harm caused by
      smoking, and some people may even develop alcoholic liver disease associated with
      inflammation, liver cirrhosis, or primary liver cancer. There are complex risk
      factors for liver injury in these people; besides ethnic and genetic factors,
      drinking volume, and drinking duration, more important factors are involved in
      the pathophysiological changes of the liver, such as the type and quality of
      alcohol, drinking pattern, socioeconomic status, and government public policy,
      which may be the determining factors for the development of alcoholic liver
      disease. On the basis of literature review, this article proposes the concept
      that "liquor does not equal to alcohol" , which has important guiding
      significance for healthy drinking and the prevention of alcoholic liver disease.

PMID- 28763853
TI  - [Focusing on the diagnosis and management of portal hypertension in cirrhosis].
AB  - Portal hypertension is one common complication with a high mortality in end-stage
      liver diseases. However, poor outcome has been shown with present therapeutic
      strategy, and the diagnosis and treatment of portal hypertension and its
      complications are research focuses. Therefore, it is necessary for clinicians and
      expert to regard diagnosis and treatment of portal hypertension patients, and to
      improve their clinical outcomes.

PMID- 28763854
TI  - [Transjugular intrahepatic portosystemic shunt for esophagogastric variceal
      bleeding in liver cirrhosis: intended population and timing].
AB  - Esophagogastric variceal bleeding is a life-threatening complication of cirrhotic
      portal hypertension. Transjugular intrahepatic portosystemic shunt (TIPS) is an
      effective method for the treatment and prevention of esophagogastric variceal
      bleeding; however, right timing of TIPS and selection of appropriate candidates
      for TIPS are of vital importance in improving patients' survival rate and
      reducing mortality rate. This article reviews the intended population and right
      timing of TIPS for the treatment and prevention of esophagogastric variceal
      bleeding in liver cirrhosis.

PMID- 28763855
TI  - [Pathophysiological basis of portal hypertension and the new concept of acute
      kidney injury in patients with liver cirrhosis].
AB  - Recently, the International Club of Ascites (ICA) has developed a new expert
      consensus on the diagnosis and treatment of acute kidney injury (AKI) in patients
      with liver cirrhosis, which reflects the new concept of AKI management in
      patients with liver cirrhosis. This consensus emphasizes the increase in the
      absolute value of serum creatinine (SCr) and establishes a new staging system for
      AKI, which may help to evaluate disease progression and recovery. In addition,
      the new management concept also emphasizes that when AKI progresses to stage 2/3
      or still progresses after comprehensive treatment, a diagnosis can be made and
      vasoconstrictors and albumin can be used as long as the patient meets the other
      diagnostic criteria for hepatorenal syndrome, regardless of SCr level.

PMID- 28763856
TI  - [Endoscopic ultrasonography: a new method for evaluation, diagnosis, and
      treatment of portal hypertension].
AB  - Through a comprehensive scan of collateral circulation establishment in portal
      hypertension, endoscopic ultrasonography (EUS) can predict the risks of
      esophageal and gastric varices, variceal bleeding, recurrence after treatment,
      and rebleeding and guide and participate in the treatment of varices. With the
      help of these advantages, EUS provides an important reference for individualized
      treatment in patients with liver cirrhosis complicated by portal hypertension and
      can improve response rate and safety. As a new method for systematic evaluation,
      diagnosis, and treatment of portal hypertension, EUS has become a new research
      hotspot in recent years.

PMID- 28763857
TI  - [Interpretations of EASL 2017 clinical practice guidelines on the management of
      hepatitis B virus infection].
AB  - The European Association for the Study of the Liver recently released the updated
      Clinical Practice Guidelines on the management of hepatitis B virus infection at
      the International Liver Congress(TM) 2017 in Amsterdam. The latest clinical
      practice guideline integrated the latest scientific advances on diagnosis and
      therapy of hepatitis B, thereby providing optimize the management of patients
      with either acute or chronic HBV. The latest clinical practice guideline includes
      new definitions of disease phases, expanded indications for initiating treatment,
      prevention of mother-to-child transmission, new stopping rules for antiviral
      therapy. Future treatment strategies to achieve 'cure' of disease and new
      biomarkers are discussed.

PMID- 28763858
TI  - [The comparison of liver inflammation and fibrosis between chronic HBV and HCV
      infection].
AB  - Objective: To explore the difference of liver inflammation and fibrosis in
      patients with chronic hepatitis B virus (HBV) infection and chronic hepatitis C
      virus (HCV) infection, and to investigate the relationship between hepatic
      pathology and alanine aminotransferase (ALT). Methods: 57 patients with chronic
      HCV infection and 346 patients with chronic HBV infection who were hospitalized
      at Shengjing Hospital of China Medical University from January 2012 to September
      2016 were enrolled. In chronic HBV infection, including 88 cases whose ALT were
      more than two times of upper limited of normal (ALT>=2*ULN) and 258 cases whose
      ALT were less than two times of upper limited of normal (ALT < 2*ULN).All the
      patients were underwent liver biopsy. Chronic HBV infection (ALT>=2*ULN and ALT <
      2*ULN) and chronic HCV infection were compared respectively. Statistical analyses
      were performed using a Univariate chi2-test and Mann-Whitney U test for
      comparison. Correlations between variables were analyzed using Spearman's rank
      correlation. Results: In chronic HBV infection group, 169 cases (48.8%) had
      inflammation grade>=2 (G>=2), 98 cases (28.3%) had fibrosis stage>=2 (S>=2), 81
      cases (23.4%) with G>=2 and S>=2.In the ALT < 2*ULN group, there were 109 cases
      (42.2%) with G>=2, 62 cases (24%) with S>=2, 49 cases (19%) with G>=2 and S>=2.
      In the ALT>=2*ULN group, 60 cases (68.2%) with G>=2, 35 cases (39.8%) with S>=2,
      31 cases (35.2%) with G>=2 and S>=2. The grade of inflammation and fibrosis have
      significantly different between ALT>=2*ULN group and ALT < 2*ULN group (chi2 =
      17.66, chi2 = 8.06, P < 0.01). In chronic HCV infection group, 47 cases (82.5%)
      with G>=2, 20 cases (35.1%) with S>=2, 20 cases (35.1%) with G>=2 and S>=2. ALT
      had no correlation with inflammation and fibrosis (P > 0.05). The grade of
      inflammation was significantly different between chronic HCV infection and
      chronic HBV infection whose ALT < 2*ULN (chi2 = 30.19, P < 0.01) but the fibrosis
      have no difference (chi2 = 2.96, P > 0.05). Compared with chronic HBV infection
      whose ALT>=2*ULN, both inflammation and fibrosis had no significantly different
      (chi2 = 3.65, chi2 = 0.32, P > 0.05 respectively). Conclusion: In chronic HBV
      infection whose ALT < 2*ULN, about 30%-40% liver tissue with significant
      necroinflammation and /or fibrosis. About 80% chronic HCV infection with
      significant necroinflammation, and the grade of inflammation has no correlation
      with ALT. The grade of inflammation has significantly different between chronic
      HCV infection group and chronic HBV infection group whose ALT < 2*ULN.

PMID- 28763859
TI  - [Influence of hepatitis B virus X gene on apoptosis of hepatic cells mediated by
      Fas].
AB  - Objective: To investigate the influence of hepatitis B virus X gene (HBx) on
      apoptosis of hepatic cells mediated by Fas in HePG2 cells. Methods: HBx
      eukaryotic vector pcDNA3.1(+)-X was transfected into HEPG2 cells with
      lipofectamine, and the null vector pcDNA3.1(+) and untransfected HEPG2 were used
      as normal controls. The cells were collected 72 h after transfection, and the
      expression of HBx mRNA and protein was determined using RT-PCR and Western blot,
      respectively. The mRNA expression of apoptosis-related genes Bcl-2 and Bax mRNA
      was also determined using RT-PCR. Cytotoxicity and apoptosis were evaluated using
      CCK-8 and flow cytometry, respectively, after HepG2-HBx and HepG2-3.1 cells were
      treated with stimulatory monoclonal antibody anti-Fas CH11. The t test was used
      for pairwise comparison. Results: The cell line HepG2-HBx was successfully
      established, as confirmed by RT-PCR and Western blot, and RT-PCR results showed
      that HepG2-HBx cells had significantly higher expression of Bcl-2 mRNA than HepG2
      3.1 and HepG2 cells (P < 0.05), but had significantly lower expression of Bax
      mRNA than HepG2-3.1 and HepG2 cells (P < 0.05); CCK-8 and flow cytometry showed
      that anti-Fas CH11 had a lower cytotoxicity to HepG2-HBx cells and allowed for a
      lower apoptosis rate of HepG2-HBx cells compared with HepG2-3.1 and HepG2 cells.
      Conclusions: HBx can inhibit apoptosis of hepatic cells mediated by the Fas
      pathway.

PMID- 28763860
TI  - [Role of enolase 1 in hepatocellular carcinoma and possible mechanism].
AB  - Objective: To investigate the role of enolase 1 (ENO1) in hepatocellular
      carcinoma (HCC) and possible mechanism. Methods: Real-time PCR and Western blot
      were used to measure the expression of ENO1 in HCC tissue, adjacent tissue,
      hepatoma cells, and normal hepatocytes. The siRNA interference technique was used
      for ENO1 knockout in HepG2 cells, and then CCK-8, colony formation assay, and
      transwell assay were used to measure the proliferation, migration, and invasion
      abilities of HepG2 cells. Real-time PCR and Western blot were used to measure the
      expression of proteins and genes involved in the activation of the Notch
      signaling pathway. The two-independent-samples t test and a one-way analysis of
      variance were used for comparison. Results: HCC tissue and HepG2 cells had
      significantly higher expression of ENO1 than adjacent tissue and normal
      hepatocytes (P < 0.05). There were significant reductions in the proliferation,
      migration, and invasion abilities of HepG2 cells after siRNA interference (P <
      0.05). There were also significant reductions in the expression of N1ICD, snail,
      slug, HEY1, HES1, and HES5 (P < 0.05). Conclusion: ENO1 may promote the
      development of HCC, possibly by participating in the regulation of the Notch
      signaling pathway.

PMID- 28763861
TI  - [A bioinformatics analysis of differentially expressed genes associated with
      liver cancer].
AB  - Objective: To investigate differentially expressed genes associated with liver
      cancer using bioinformatics methods, and to screen out molecular markers for
      early diagnosis of liver cancer and potential molecular targets for
      immunotherapy. Methods: The microarray data associated with liver cancer were
      downloaded from Gene Expression Omnibus. JMP software was used for correlation
      analysis of GSE datasets, Limma program in R language was used to screen out
      differentially expressed genes, and the Gene Ontology (GO) enrichment analysis
      and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were performed
      for differentially expressed genes. A protein-protein interaction (PPI) network
      was also established for analysis. An analysis of specific expression associated
      with liver cancer was performed with reference to RNA-seq transcriptome data for
      other tumors obtained from TCGA to further identify specific differentially
      expressed genes in liver cancer, and a survival curve analysis was performed for
      patients with liver cancer. Results: A total of 92 differentially expressed genes
      were identified, with 21 upregulated genes and 71 downregulated genes. Through
      the GO, KEGG, and PPI analyses, RNA-seq data verified that only glypican 3 (GPC3)
      was upregulated in liver cancer, and MBL2, SDS, SLCO1B3, TDO2, SAA4, and SPP2
      were downregulated. Conclusions: GPC3 might act as a target for immunotherapy,
      and other molecular markers may become molecular markers for early detection of
      liver cancer and potential targets for immunotherapy.

PMID- 28763862
TI  - [A screening system for anti-metastatic small-molecule compounds based on
      perinucleolar compartment prevalence in liver cancer cells].
AB  - Objective: To establish a screening system for anti-metastatic small-molecule
      compounds based on perinucleolar compartment (PNC) prevalence in liver cancer
      cells and to investigate its validity. Methods: Polypyrimidine tract-binding
      protein (PTB) monoclonal antibody was used to measure the PNC prevalence in
      HepG2, HepG2M, and Huh7 cells, and wound healing assay and transwell assay were
      used to analyze the migration and invasion abilities of hepatoma cells. HepG2M
      cells were used as the model for the screening of anti-metastatic small-molecule
      compounds, and after the treatment with the compounds A1, A4, and E696, qPCR was
      used to measure the expression of metastasis-related miRNAs (miR-141 and miR
      200c). A one-way analysis of variance was used for comparison of data between
      multiple groups. Results: PTB immunofluorescence assay showed that HepG2M cells
      had the highest PNC prevalence, followed by Huh7 and HepG2 cells, and PNC
      prevalence was positively correlated with the metastasis and invasion abilities
      of hepatoma cells. The PNC prevalence of HepG2M cells was reduced to 22.88% +/
      4.61% by A1, 14.22% +/- 3.05% by A4, and 26.12% +/- 4.94% by E696. Wound healing
      assay showed that the 48-hour scratch ratio increased from 17.70% +/- 3.34% to
      64.50% +/- 2.65%, 83.40% +/- 5.10%, and 57.20% +/- 3.06% (F = 171.1, P < 0.01),
      respectively. Transwell assay showed that the number of invasive cells was
      reduced from 264.33 +/- 30.50 to 104.33 +/- 13.50, 58.00 +/- 11.00, and 111.33 +/
      19.50 (F = 59.87, P < 0.01), respectively. The anti-metastatic effect of these
      three compounds was positively correlated with their ability to destroy PNC. A4
      upregulated the expression of miR-141 and miR-200c in a dose-dependent manner,
      and after HepG2M cells were treated with A4 at a concentration of 5 MUM, 10 MUM,
      or 20 MUM, the level of miR-141 was increased to 3.61 +/- 0.78, 8.12 +/- 1.15,
      and 18.24 +/- 2.44 folds (F = 88.01, P < 0.01), respectively, and that of miR
      200c was increased to 2.82 +/- 0.43, 4.82 +/- 0.89, and 10.74 +/- 1.22 folds (F =
      87.94, P < 0.01), respectively. Conclusion: The screening system for anti
      metastatic small-molecule compounds based on PNC prevalence can provide an
      effective technical platform for research and development of anti-metastatic
      drugs for liver cancer.

PMID- 28763863
TI  - [Influence of phosphoglycerate kinase 1 on metastasis and invasion of hepatoma
      cells and prognosis of liver cancer].
AB  - Objective: To investigate the association between expression of phosphoglycerate
      kinase 1 (PGK1) in liver cancer tissue and prognosis, as well as its influence on
      metastasis and invasion of hepatocellular carcinoma (HCC) cells. Methods:
      Overexpression and downregulated expression of PGK1 in HCC cells were mediated by
      lentivirus to establish hepatoma cell lines with different expression levels of
      PGK1. The Transwell chamber invasion assay, wound healing assay, and colony
      forming assay were used to investigate the influence of PGK1 on metastasis,
      invasion, and proliferation of HCC cells. Immunohistochemistry was used to
      measure the expression of PGK1 in liver cancer tissue samples from 116 patients
      with hepatocellular carcinoma who underwent radical surgery, and the Kaplan-Meier
      method and the log-rank test were used to determine the association between PGK1
      expression and prognosis of patients with liver cancer. Results: HCCLM3 and
      MHCC97H HCC cells with high metastatic potential had significantly higher
      expression of PGK1 than Hep3B and Huh7 HCC cells with low metastatic potential.
      Downregulation of PGK1 expression significantly inhibited the migration (31.2% +/
      2.4% vs 12.0% +/- 1.3%, t = 21.57, P < 0.01), invasion (58 +/- 11 vs 21 +/- 8, t
      = 4.687, P < 0.05), and colony-forming ability (168.6 +/- 15.1 vs 118.4 +/- 8.1,
      t = 6.650, P < 0.05) of MHCC97H cells, while overexpression of PGK1 enhanced the
      migration (62.8% +/- 4.4% vs 83.6% +/- 6.1%, t = 20.56, P < 0.01), invasion (80
      +/- 12 vs 121 +/- 15, t = 4.603, P < 0.05), and colony-forming ability (52.3 +/-
      8.6 vs 84.7 +/- 9.0, t = 27.18, P < 0.01) of Hep3B cells. The high PGK1
      expression group had significantly shorter median disease-free survival time and
      mean survival time than the low PGK1 expression group (22.00 +/- 8.51 vs not
      reached, P < 0.05; 46.00 +/- 16.87 vs not reached, P < 0.01). Conclusions: PGK1
      is involved in the regulation of metastasis and invasion of HCC cells and can
      promote the migration and invasion of HCC cells. Therefore, PGK1 may be an
      important predictor of prognosis and postoperative recurrence in patients with
      liver cancer.

PMID- 28763864
TI  - [High expression of hnRNPAB/Kap1 together promote poor prognosis in HCC].
AB  - Objective: To further understand the interaction protein spectrum of
      heterogeneous ribonucleoprotein AB (hnRNP AB), and to investigate their clinical
      significance in hepatocellular carcinoma (HCC). Methods: We carried out mass
      spectrometry to reveal the specific peptides of KRAB-associated protein 1 (Kap1)
      and hnRNPAB, and verified their interaction by immunocoprecipitation and western
      blotting. Expression of hnRNPAB/Kap1 proteins were detected by
      immunohistochemical staining in the tissue microarrays. Categorical data were
      analyzed by the chi square test or Fisher exact test; enumeration data between
      groups were compared using Student t-test or Wilcocon signed rank test; the
      cumulative recurrence and survival rates were evaluated using the Kaplan-Meier
      method and the differences were assessed using the log-rank test. Results: We
      identified Kap1 as a molecular partner for hnRNPAB in HCCLM3 cells and HepG2
      cells as well. We found that the 5-year survival rate of the Kap1high patients
      was significantly lower than the survival rate of those of the Kap1low group (36%
      vs 59% , HR = 1.67, P < 0.001). Similarly, Kap1high HCC patients had the poorest
      prognosis at 5-years, with higher cumulative recurrence rate than Kap1low
      patients (72% vs 54%, HR = 1.66, P = 0.001). Univariate and Multivariate analyses
      revealed that hnRNPAB /Kap1 alone (HR = 1.35 /1.28, P = 0.001) or in combination
      with Kap1 (HR =1.24 /1.27, P < 0.05) were independent prognostic indicators for
      overall survival and time to recurrence. Conclusion: In HCC cells, hnRNPAB and
      Kap1 form protein complexes. The expression levels of hnRNPAB alone or in
      combination with Kap1 in HCC patients are important because they provide not only
      a predictor for HCC prognosis but also a therapeutic target for future studies.

PMID- 28763865
TI  - [Effect of platycodin D on radiosensitivity of human hepatoma cell line and
      related mechanisms of action].
AB  - Objective: To investigate the effect of platycodin D on the radiosensitivity of
      human hepatoma cell lines HepG2 and SMMC-7721 and related mechanisms of action.
      Methods: MTT assay was used to analyze the effect of different concentrations of
      platycodin D with different treatment times on cell viability. The cells were
      pretreated with 5 MUg/ml platycodin D for 24 hours followed by X-ray irradiation
      at different radiation doses. Colony-forming assay was used to measure the
      radiosensitizing effect of platycodin D on cells. The quasi-threshold dose (Dq),
      mean lethal dose (Do), extrapolation number (N), sensitizer enhancement ratio
      (SER), and survival fraction (SF) at different radiation doses were calculated,
      and the multi-target single-hit model was used to fit the cell survival curve
      according to the formula SF = l-(l-e(-D/D0))N. Flow cytometry was used to
      investigate the distribution of cell cycle, and Western blotting was used to
      measure the changes in the protein expression of phosphorylated
      phosphatidylinositol 3'-kinase (pPI3K), phosphorylated protein kinase (pAkt),
      nuclear factor-kappaB (NF-kappaB), and phosphorylated nuclear factor inhibiting
      protein (pIkappaBalpha). A one-way analysis of variance, the t-test, or the least
      significant difference test was used for statistical analysis based on the type
      of data. Results: Platycodin D reduced the viability of HepG2 and SMMC-7721 cells
      in a dose-dependent manner; the IC50 value for HepG2 cells was 24.2 +/- 0.61
      MUg/ml at 24 hours and 7.68 +/- 0.46 MUg/ml at 48 hours, and that for SMMC-7721
      cells was 23.8 +/- 0.57 MUg/ml at 24 hours and 8.63 +/- 0.86 MUg/mL at 48 hours.
      After the combined treatment with platycodin D and irradiation, there were
      significant reductions in Dq (P = 0.002), Do (P = 0.002), and N value (P =
      0.003), the survival curve markedly shifted to the left, and SER was 1.347 +/-
      0.04 in HepG2 cells and 1.418 +/- 0.05 in SMMC-7721 cells. In addition,
      platycodin D significantly inhibited the increase in the proportion of cells in
      G2/M phase, the increases in the protein expression of pPI3k (P = 0.002), pAkt (P
      = 0.003), and NF-kappaB (P = 0.002), and the reduction in the protein expression
      of pIkappaBalpha (P = 0.003). Conclusion: Platycodin D can increase the
      radiosensitivity of HepG2 or SMMC-7721 cells, possibly by enhancing the growth
      inhibition effect of irradiation and inhibiting the activation of the PI3k/Akt
      and NF-kappaB pathways.

PMID- 28763866
TI  - [Effect of sclerotherapy on esophageal varices in cirrhotic patients with
      diabetes: a prognostic analysis].

PMID- 28763867
TI  - [Clinical and predictive effects of alpha-2a-pegylated interferon in inactive
      HBsAg carriers].

PMID- 28763868
TI  - [A case of HBV reactivation after chemotherapy for non-Hodgkin's lymphoma in an
      anti-HBs/anti-HBc-positive patient].

PMID- 28763869
TI  - [A case of renal artery stenosis induced by sorafenib].

PMID- 28763870
TI  - [Effect of liraglutide in treatment of non-alcoholic fatty liver disease:
      mechanism of action and research advances].
AB  - Non-alcoholic fatty liver disease is a common chronic liver disease closely
      associated with obesity, hyperlipidemia, and diabetes. It can gradually progress
      to liver cirrhosis or even hepatocellular carcinoma; however, there are still no
      specific therapeutic agents for this disease. Liraglutide is a human glucagon
      like peptide-1 analogue and has a marked effect in the treatment of type 2
      diabetes. At present, many studies indicate that liraglutide also has a certain
      therapeutic effect on non-alcoholic fatty liver disease during the treatment of
      type 2 diabetes, but its mechanism of action remains unknown. This article
      reviews the known mechanisms of action of liraglutide in the treatment of non
      alcoholic fatty liver disease.

PMID- 28763871
TI  - [The function of Aurora A and its role in the development of liver cancer].
AB  - Aurora A plays a key role in cellular mitosis. It is located in the centrosome
      and spindle, and is mainly involved in the processes of centrosome maturation and
      separation, bipolar spindle assembly, and the regulation of mitotic progression.
      Recent studies have suggested that Aurora A is involved in tumorigenesis and
      tumor development through multiple mechanisms. Overexpression of Aurora A could
      cause abnormal centrosome amplification, aneuploidy formation, and G2/M
      checkpoint defects, which result in chromosome instability and imbalance between
      cell division and apoptosis, and eventually leads to abnormal cell proliferation.
      Aurora A also participates in the regulation of the p53 and BRCA1 pathways,
      leading to suppressor gene dysfunction and changes in cell viability, and it
      induces telomerase activity by upregulating c-Myc, resulting in tumorigenesis. In
      addition, Aurora A also induces drug resistance in liver cancer cells. Thus,
      Aurora A has gradually become a new target for cancer therapy in recent years.
      This paper has summarized the recent studies on Aurora A, and reviewed its
      biological functions in cell mitosis and roles in liver tumorigenesis.

PMID- 28763872
TI  - [Research of the biomarkers in pulmonary and extrapulmonary acute respiratory
      distress syndrome].
AB  - Objective: To explore the biomarkers that applied to pulmonary acute respiratory
      distress syndrome (ARDS) and extrapulmonary ARDS respectively. Methods: A total
      of 49 eligible patients with ARDS were selected from Department of Respiratory
      intensive care unite (ICU) , Department of General ICU and Department of
      Emergency ICU, the Second Affiliated Hospital of Nanchang University, during
      April 2015 and February 2016, and divided into pulmonary ARDS group (n=26) and
      extrapulmonary ARDS group (n=23) according to primary causes. Totally 19 cases
      from healthy examination personnel were served as control. Acute physiology and
      chronic health evaluation III (APACHE III) score and lung injury score of all
      hospitalized patients were completed within 24 hours after the diagnosis of ARDS
      and the serum levels of angiogenin2 (Ang-2) , surfactant protein D (SP-D),
      soluble receptor for advanced glycation end products (sRAGE), Krebs von den
      Lungen-6 (KL-6) were measured. Then the 28-day outcomes were observed. The serum
      levels of the biomarkers were compared between each group and correlation
      analysis was conducted between different indexes. Finally, The relationship
      between the four biomarkers and the outcome of each group was analyzed. Results:
      The serum level of Ang-2 in pulmonary ARDS group and extrapulmonary ARDS group
      was significantly higher than that in control group[1 462 (569, 3 638) and 4 568
      (2 236, 8 457) vs 460 (389, 578) ng/L, all P<0.05], and the serum level of Ang-2
      was significantly higher in extrapulmonary ARDS group than that in pulmonary ARDS
      group (P<0.05). The serum level of SP-D in pulmonary ARDS group and
      extrapulmonary ARDS group was significantly higher than that in control group[5.9
      (2.5, 22.7) mg/L and 3.7 (1.7, 6.5) vs 1.9 (0.6, 4.4) mg/L, all P<0.05], and the
      serum level of SP-D was significantly higher in pulmonary ARDS group than that in
      extrapulmonary ARDS group (P<0.05). The serum level of sRAGE in pulmonary ARDS
      group and extrapulmonary ARDS group was significantly higher than that in control
      group[238 (101, 583) and 229 (114, 443) vs 117 (88, 176) ng/L, all P<0.05]. The
      serum level of KL-6 in pulmonary ARDS group was significantly higher than that in
      control group[10 435 (3 401, 17 607) vs 4 780 (3 962, 5 320) U/L, P<0.05].
      Increased serum levels of SP-D (OR=1.089, 95% CI: 1.001-1.085) and KL-6
      (OR=1.206, 95% CI: 1.016-1.432) at the early stage were the independent
      prognostic factors for the 28-day mortality for pulmonary ARDS. Advanced age
      (OR=2.622, 95% CI: 1.046-6.574) was the independent prognostic factor for the 28
      day mortality for extrapulmonary ARDS. Conclusion: SP-D and KL-6 may be the serum
      biomarkers of pulmonary ARDS and Ang-2 may be the serum biomarker of
      extrapulmonary ARDS.

PMID- 28763873
TI  - [Long-term oncologic outcomes of localized high-risk prostate cancer undergoing
      brachytherapy combined with external-beam radiation therapy and maximal androgen
      blockade].
AB  - Objective: To investigate the oncologic outcome and PSA kinetics of localized
      high-risk prostate cancer (PCa) patients treated with combination strategy of
      radiation therapy (RT) and maximal androgen blockade (MAB). Methods: We
      retrospectively reviewed the clinical data of 320 localized PCa patients
      undergoing RT+ MAB from 2001 to 2015. And radiation treatment protocol consisted
      of permanent prostate brachytherapy (PPB) at 110 Gy and EBRT at 45 Gy/23
      fractions. Results: The median follow-up time was 90 (range: 12-186) months. And
      117 (36.6%) cases underwent MAB + external-beam radiotherapy (EBRT), and other
      203 (63.4%) cases received MAB+ EBRT+ PPB. Multivariate Cox regression analyses
      showed that PSA kinetics were positive indicators of oncologic outcomes.
      Furthermore, PSA kinetics were aberrantly improved by supplemental PPB to MAB+
      EBRT as following, PSA nadir (1.3+/-0.7)MUg/L vs(0.11+/-0.06)MUg/L, time of PSA
      decrease to nadir (7.5+/-1.8)months vs (3.2+/-2.1)months, PSA doubling time
      (15.6+/-4.2)months vs (22.6+/-6.1)months, PSA decreasing amplitude (84.6+/
      6.2)%vs(95.8+/-3.4)%. Additionally, the median time of several important
      oncologic events in MAB+ EBRT+ PPB group were also prolonged than that in MAB+
      EBRT group as following, overall survival (12.3 years vs 9.1 years, P<0.001),
      biochemical recurrence-free survival (9.8 years vs 6.5 years, P<0.001), skeletal
      related event (10.4years vs 8.2 years, P<0.001), and cytotoxic chemotherapy (11.6
      years vs 8.8 years, P=0.007). Conclusion: MAB+ EBRT+ PPB is extremely effective
      combination strategy for localized high-risk PCa patients, and PPB plays the
      important synergistic role in improving PSA kinetics, which are independent
      predictor for oncologic outcomes.

PMID- 28763874
TI  - [Correlation between serum uric acid level and acute renal injury after coronary
      artery bypass grafting].
AB  - Objective: To evaluate whether early postoperative serum uric acid level can
      predict postoperative acute renal injury (AKI) among patients undergoing coronary
      artery bypass grafting (CABG). Methods: The study retrospectively enrolled 1 306
      patients undergoing CABG in Fuwai Hospital between September 2012 and December
      2013. The patients were divided into 5 groups by the concentrations of serum uric
      acid measured on the morning of the first postoperative day, and uric acid
      categories were as follow: less than 195 MUmol/L (Q1 group, 262 cases), 195-236
      MUmol/L (Q2 group, 263 cases), 237-280 MUmol/L (Q3 group, 260 cases), 281-336
      MUmol/L (Q4 group, 261 cases), more than 336 MUmol/L (Q5 group, 260 cases). The
      primary end points were AKI (RIFLE criteria), severe AKI (AKI>=stage I),
      postoperative continuous renal replacement therapy (CRRT) requirement, in
      hospital death, length of stay in hospital and intensive care unit(ICU). The area
      under the receiver-operating characteristic (ROC) curve (AUC) was used to
      determine the ability of the early postoperative serum uric acid level as a risk
      factor for postoperative AKI prediction. Results: Among the 1 306 patients
      enrolled in the study, AKI was found in 335 patients (25.65%). After adjusting
      for variables that were different between the 5 groups, the Q5 group had
      significantly higher risk of AKI, AKI>= stage I and the requirement of CRRT
      (P<0.01). The ROC for the outcome of postoperative AKI had an AUC of 0.648 (95%
      CI: 0.612-0.683) when serum creatinine levels alone were used and 0.722 (95% CI:
      0.688-0.755) when serum uric acid levels alone were used (both P<0.001). Early
      postoperative serum uric acid was a better predictor than serum
      creatinine(P<0.001). Conclusion: The serum uric acid concentration within 12
      hours after operation is an independent predictor of postoperative AKI in
      patients undergoing CABG, which could be used to identify patients at high risk
      for AKI.

PMID- 28763875
TI  - [A clinical study on the effect of nattokinase on carotid artery atherosclerosis
      and hyperlipidaemia].
AB  - Objective: To evaluate the efficacy of oral nattokinase (NK) in the reduction of
      common carotid artery intimal medial thickness (CCA-IMT) and carotid artery
      plaque size and in lowering blood lipids, and to explore the underlying mechanism
      of actions of NK and its potential clinical use. Methods: All enrolled patients
      were from the Out-Patient Clinic of the Department of TCM at the 3(rd) Affiliated
      Hospital of Sun Yat-sen University. Using randomised picking method, all patients
      were randomly assigned to one of two groups, NK and Statin (ST) group. NK Group
      patients were given NK at a daily dose of 6 000 FU and ST Group-patients were
      treated with statin (simvastatin 20 mg) daily. The treatment course was 26 weeks.
      CCA-IMT, carotid plaque size and blood lipid profile of the patients were
      measured before and after treatment. Results: A total of 82 patients were
      enrolled in the study and 76 patients (NK 39, ST 37) completed the study.
      Following the treatments for 26 weeks, there was a significant reduction in CCA
      IMT and carotid plaque size in both groups compared with the baseline before
      treatment. The carotid plaque size and CCA-IMT reduced from(0.25+/-0.12)cm(2) to
      (0.16+/-0.10)cm(2) and from (1.13+/-0.12)mm to (1.01+/-0.11)mm, repectively. The
      reduction in the NK group was significantly profound (P<0.01, 36.6% reduction in
      plaque size in NK group versus 11.5% change in ST group). Both treatments reduced
      total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and
      triglyceride (TG). While the reduction in both groups was shown to be
      statistically significant (P<0.01), the reduction of TC, LDL-C and TG in ST group
      was significantly greater (P<0.05). In addition, NK significantly increased the
      level of high-density lipoprotein cholesterol (HDL-C) (P<0.05), in contrast, HDL
      C in the ST group did not change. The lipid lowering effect observed in the NK
      group was not correlated to the reduction of CCA-IMT and carotid artery plaque
      size (r=0.35, P=0.09). Conclusions: Our findings from this pioneer clinical study
      suggests that daily NK supplementation is an effective way to manage the
      progression of atherosclerosis and potentially may be a better alternative to
      statins which are commonly used to reduce atherosclerosis and further to prevent
      cardiovascular attack and stroke in patients. The mechanism underlying the
      reduction of carotid atherosclerosis by NK may be independent from its lipid
      lowering effect, which is different from that of statins.

PMID- 28763876
TI  - [Quantitative measurement of oxalic acid in urine by liquid chromatography
      combined with tandem mass spectrometry].
AB  - Objective: To find a suitable method for the determination of oxalic acid in the
      urine of patients with stones, in order to provide a new method and basis for the
      prevention and treatment of stone. Methods: Liquid chromatography combined with
      tandem mass spectrometry was used to analyze oxalic acid in urine directly.The
      accuracy, stability, repeatability and other indicators of the results were
      tested. Results: The results showed a good linear relationship with the
      concentration of oxalic acid in urine. y=58.524x-15.246 (R(2)=0.979 02). The
      results were stable, reproducible (the intra-day and inter-day coefficient of
      variation was less than 10% and 15%, respectively), and the accuracy was
      comparable with that of the enzyme method (N=20, R=0.93). Conclusion: Using the
      method of this study to detect the content of oxalic acid in urine has the
      advantages of simple operation, good repeatability, accurate results, and low
      price. It is worth to be popularized and applied in clinical practice.

PMID- 28763877
TI  - [Efficacy of PVD regimen combined with IMRT for early-stage extranodal nasal NK/T
      cell lymphoma].
AB  - Objective: To evaluate the efficacy of PVD chemo-regimen (Pegaspargase,
      vincristine and dexamethasone) combined with intensity-modulated radiotherapy
      (IMRT) for patients with early-stage extranodal nasal NK/T-cell lymphoma (ENKL).
      Methods: Clinical data of 52 patients with early-stage ENKL were collected during
      May 2010 and June 2015 in Department of Lymphoma, Cancer Hospital of Guizhou
      Medical University, and these patients firstly received a concurrent
      chemoradiotherapy of two-cycle of PVD and IMRT (gross tumor volume primary: 12.6
      59.4 Gy) and then 2 to 4 cycles of PVD as subsequent chemotherapy, the efficacy
      and adverse responses were retrospectively analyzed and observed. Results: Follow
      up stopped until December 2015, complete remission was seen in 44 cases (84.6%)
      and partial remission 7 cases (13.5%), out of 52 cases. A total of 1 case died of
      progression disease during treatment and within 1 year after treatment, 1 case
      died of pulmonary infection within 1 week after treatment, 2 cases survived with
      tumor; so the objective response rate and clinical benefit rate were both 98.1%,
      1-year, 2-year and 3-year overall survival rates and progression free survival
      rates were all 93.6%, 1-year and 2-year disease free survival rates were both
      90.3%; the correlation analysis showed that the radiotherapy dose was related to
      the curative effect (P<0.05). Short term adverse responses were observed in 6
      cases (11.5%) with grade 3 leucocytopenia, in 5 cases (9.6%) with grade 3-4
      dyslipidemia and in 2 cases (3.8%) with grade 3 hypoalbuminemia during
      chemoradiotherapy. All the patients had different degrees of radiation oral
      mucositis and radiation dermatitis. Conclusion: For early-stage ENKL, a
      concurrent chemoradiotherapy of PVD regimen and IMRT have a good therapeutic
      effect and adverse response can be tolerated.

PMID- 28763878
TI  - [Glabridin attenuates MPTP-induced parkinson disease by inhibiting extracellular
      regulated protein kinases signaling pathway].
AB  - Objective: To investigate whether Glabridin had a beneficial effect on 1-methyl-4
      phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) induced parkinson disease (PD) in
      mice, and explore the possible underlying mechanisms. Methods: Forty C57BL/6N
      mice were randomly assigned into control group, MPTP group, Glabridin
      therapy(MPTP+ GLA)group, Levodopa therapy(MPTP+ LD)group, with 10 in each group.
      PD model was induced by intraperitoneal administration of MPTP(20 mg/kg). The
      mice in MPTP+ GLA group, MPTP+ LD group and control group were gavaged by
      glabridin (50 mg/kg), levodopa (40 mg/kg), and equal volume of normal saline,
      respectively. The behavioral changes of each group were observed and Y-type
      electric maze test was performed. The levels of tumor necrosis factor-alpha (TNF
      alpha) and interleukin-18 (IL-18) were assayed by enzyme-linked immunosorbent
      assay (ELISA). Malondialdehyde (MDA), and superoxide dismutase (SOD) were
      analyzed. The protein expression of tyrosine hydroxylase (TH) and extracellular
      signal regulated protein kinase (ERK) protein expression of hippocampus tissue
      was detected using immunohistochemical techniques. TH and pERK protein expression
      of hippocampus tissue were detected by Western blotting. Results: Mice in MPTP
      group showed typical behavior of PD, and the ability of learning and memory was
      significantly lower than those in the control group. Compared with MPTP group,
      the expressions of TNF-alpha and IL-18 were suppressed by GLA in hippocampus[TNF
      alpha(MUg/L): 84.04+/-18.66 vs 106.53+/-28.54; IL-18(MUg/L): 42.34+/-6.01 vs
      58.42+/-8.39]. The levels of MDA in hippocampus were down-regulated significantly
      in groups administrated with GLA[MDA(nmol/mgprot): 2.64+/-0.52vs 3.78+/-0.31],
      while the SOD level increased after GLA administration[SOD(U/mgprot): 93.45+/
      9.59 vs 77.83+/-8.98]. The results of immunohistochemistry showed the expression
      of TH protein in MPTP group was significantly decreased compared with that in
      control group, while the p-ERK protein in MPTP group was significantly increased.
      In MPTP+ GLA group and MPTP+ LD group, the expression of TH protein was
      significantly higher than that in MPTP group, and the expression of p-ERK protein
      was significantly lower than that in MPTP group. Western blot results showed that
      compared with control group, the expression of TH was significantly decreased,
      and p-ERK protein in hippocampus was significantly higherin MPTP group. The
      expression of TH protein was significantly higher in MPTP+ GLA group than that in
      MPTP group, while the expression of p-ERK protein were inhibited by GLA in MPTP
      induced PD mice. Conclusion: Traditional Chinese medicine glabridin can protect
      the learning and memory ability of PD mice induced by MPTP by inhibition of the
      ERK signal pathway, antioxidation and reduction of inflammation.

PMID- 28763879
TI  - [Study of fraction amplitude of low frequency fluctuation on resting-state
      functional magnetic resonance imaging in adultperipheral facial paralysis].
AB  - Objective: To analysis the change of brain functional activity in the left and
      right peripheral facial paralysis by using resting-state functional magnetic
      resonance imaging (R-fMRI) of fraction amplitude of low frequency
      fluctuation(fALFF) measurement technique, and research the abnormal brain region
      with different side patients whether there are differences. Methods: A total of
      43 patients with peripheral facial paralysis patients (patient groups, divided
      into left / right two subgroups) and 21 healthy volunteers (control group) in
      this study.Resting-state fMRI were acquired for each volunteer and patient. The
      fALFF approach was used to compare the peripheral facial paralysis groups to
      healthy group.Functional analysis was performed with brain function analysis
      software REST and DPARSFA , and then analysis the difference of two groups of
      patients and control group in two sample t test.At the same time, the correlation
      analysis between fALFF parameters map of the left and right side of two groups of
      patients and corresponding facial nerve grading TFGS score.Ultimately obtain a
      statistically significant brain regions. Results: Compared to healthy group, the
      decreased fALFF areas in the left side facial paralysis were showed in the right
      superior temporal gyrus , the pole of the right temporal, right middle temporal
      gyrus, the left occipital gyrus, and left medial cingulate gyrus, left
      paracentral lobule, and the left supplementary motor area; while the increased
      brain regions have the right superior frontal gyrus, right middle frontal gyrus,
      the right precentral gyrus, bilateral inferior temporal gyrus and middle temporal
      gyrus.Compared to healthy group, the decreased fALFF areas in the right side
      facial paralysis were showed in the right inferior temporal gyrus and fusiform
      gyrus, the left inferior occipital gyrus, the left superior parietalgyrus, the
      left inferior parietalgyrus, left precuneus, left paracentral lobule, the left
      supplementary motor area; while the increased brain regions have the left
      Calcarine, right lingual gyrus, corpus callosum, right medial cingulum gyrus.In
      the left facial paralysis group TFGS score was positively correlated with brain
      regions have left middle frontal gyrus, left precuneus and left cuneus, while the
      negatively related brain area on the right lingual gyrus.In the right facial
      paralysis groups TFGS score was positively correlated with brain areas have right
      inferior temporal gyrus and middle temporal gyrus, left inferior parietalgyrus;
      while the negatively correlated brain area on the left superior temporal gyrus,
      the right medial frontal gyrus. Conclusion: The left and right side facial
      paralysis patient's mood and motor function integration mechanism may be
      different, and the patient's emotional and psychological changes may be
      associated with disease severity.

PMID- 28763880
TI  - [Clinical significance of serum resistin in patients with generalized myasthenia
      gravis].
AB  - Objective: To detect the serum resistin levels in patients with generalized
      myasthenia gravis (GMG) and evaluate the clinical values of resistin. Methods: We
      detected the serum resistin levels in 58 patients with GMG and 58 healthy
      controls (HC) from January 2013 to December 2015 in Tianjin medical university
      general hospital.Then we analyzed the correlation of the serum resistin levels
      with the clinical features. Results: The serum resistin levels in patients with
      GMG, (8.26+/-4.27) ng/ml, was significantly higher than in HC, (4.12+/-1.36)
      ng/ml, (P<0.001). There was no statistical difference of the serum resistin
      levels between female or male patients with GMG (P=0.589). The serum resistin
      levels in patients with GMG was positively correlated with the quantitative MG
      score for disease severity (QMG) (r=0.446, P<0.001), but not correlated with age
      (r=0.168, P=0.206). The patients with higher resistin levels took higher risk of
      combining with thymoma (P=0.002), 56.5%, and these patients had higher QMG, 11(5)
      (P=0.001); and the ratio and QMG in the patients with lower resistin levels were
      17.1%, 7(5), respectively.The GMG patients with thymoma (TGMG+ ) had remarkably
      higher serum resistin levels, (10.7+/-5.3) ng/ml (P=0.010) and the QMG score,
      11(5) (P<0.001) than the GMG patients without thymoma (TGMG-) with (7.0+/-3.1)
      ng/ml and 8(5). Conclusion: Resistin is probably associated with the severity of
      the disease of MG, and maybe a potential biomarker of MG combined with thymoma.

PMID- 28763881
TI  - [Efficacy and tolerance of Memantine monotherapy and combination therapy with
      Reinhartdt And Sea Cucumber Capsule on agitation in moderate to severe Alzheimer
      disease].
AB  - Objective: To explore the efficacy and tolerance of Memantine combined Reinhartdt
      And Sea Cucumber Capsule (R.S.C) on treating agitation in patients with moderate
      severe Alzheimer disease (AD). Methods: One hundred and fifty-eight moderate
      sever AD patients from Sep.2013 to Sep.2014 in Zhejiang Provincial People's
      Hospital were randomly divided into two groups: group of Memantine combined R.
      S.C and group of single Memantine. Then Mini-Mental Sate Examination (MMSE) and
      Neuropsychiatric Inventory (NPI) were used to evaluate cognition symptom,
      behavioral and psychological symptoms of dementia (BPSD) and agitation symptom at
      the baseline and the end of 24 weeks.The Treatment Emergent Symptom Scale (TESS)
      was used to assess adverse reaction and tolerance.At last, the data was analyzed
      by chi-square test, t-test and covariance test. Result: At the terminal of
      experience, the total NPI scores and agitation factor decreased markedly in both
      of the two groups (P<0.05). Among the patients who had agitation symptom at the
      baseline, the total NPI scores and agitation factor (18+/-5, 3.7+/-2.6) in group
      of Memantine combined R. S.C were notably lower than those in the group of single
      Memantine (21+/-6, 5.3+/-2.5) (P<0.05). The incidence of adverse reaction between
      the two groups had no significant difference (combined treatment group was 27.7%,
      single treatment group was 23.2%). One patient dropped out because of skin
      allergy, and most adverse reactions were tolerant. Conclusions: Both two groups
      are effective in agitation and BPSD, and Memantine combined R. S.C is better than
      single treatment.R.S.C dose not aggravate adverse reaction and can be well
      tolerated.

PMID- 28763882
TI  - [Analysis of a Chinese Charcot-Marie-Tooth disease type 2D pedigree].
AB  - Objective: To achieve definite diagnosis in a clinically diagnosed Charcot-Marie
      Tooth disease (CMT) pedigree and broaden the mutational diversity of CMT-related
      mutations in Chinese Han population. Methods: Patients clinically diagnosed with
      CMT were recruited from Department of Neurology, Chinese PLA General Hospital
      between December, 2012 to June, 2016. Clinical examination, laboratory tests,
      nerve conduction studies, and molecular and bioinformatics analyses were
      performed on a clinically diagnosed CMT pedigree. Results: In the pedigree, a
      GARS mutation (c.794C>T, p. S265F) was identified and CMT2D was diagnosed.
      Conclusion: The newly identified GARS mutation has broaden the mutational
      diversity of CMT2D in Chinese Han population.

PMID- 28763883
TI  - [Association between the ApoB/A1 ratio and the vulnerability of LMCA plaque in
      the patients with stable angina pectoris].
AB  - Objective: To investigate the relationship between ApoB/A1 ratio and the
      characteristics of tissue components of their left main coronary
      artery(LMCA)plaque. Methods: A total of 98 patients with stable angina pectoris
      who received chronic statin treatment underwentpercutaneous coronary intervention
      in the People's Hospital of Henan Province from June 2010 to June 2016 were
      included.We prospectively performed intravascular ultrasound virtualhistology
      (IVUS-VH) to their LMCA and evaluated the tissue characteristics, and the blood
      level of total cholesterol (TC) and low-density lipoprotein cholesterol(LDL-C),
      high-density lipoprotein cholesterol(HDL-C), triglyceride(TG), LDL-C/HDL-C ratio,
      ApoB, ApoA1, ApoB/A1 ratio were measured, then the association of the tissue
      characteristics with the aboved lipids values were analyzed. Results: According
      to the median value of their ApoB/A1ratios (0.80), they were divided into 2
      groups [high ApoB/A1 ratio (>0.80) (n=49) and low ApoB/A1 ratio (<=0.80) (n=49)].
      The patients with a high ApoB/A1 ratio had alarger fibrolipid volume and a
      smaller fibrous volume compared to patients with a low ApoB/A1 ratio ( 17.5%+/
      1.2% vs 9.0%+/-1.0%, P=0.03 and 55.1%+/-2.1% vs 63.9%+/-1.8%, P<0.01). Using
      multivariate linear regression analysis after adjustment for the above-mentioned
      confounding factors, the ApoB/A1 ratio had a significantly positive correlation
      with fibrolipid volume (r=0.445, beta=0.29, P=0.010)and had a negative
      correlation with fibrous volume (r=-0.567, beta=-0.32, P=0.011), suggesting that
      the ApoB/A1 ratio was associated with the vulnerability of the LMCA plaque.
      Conclusion: For the patients with stable angina pectoris and chronic treatment of
      statins, a high ApoB/A1 ratio is associated with a high percentage of fibrolipid
      volume and a low percentage of fibrous volume in LMCA lesions, suggesting that
      the ApoB/A1 ratios could predict the vulnerability of the LMCA plaque.

PMID- 28763884
TI  - [Application study of qualitatively diagnosing prostate cancer using ultrahigh b
      value DWI].
AB  - Objective: To explore the value of ultrahigh b-value DWI in diagnosis of prostate
      cancer. Methods: From October 2015 to October 2016, a total of 84 cases from
      Affiliated Changshu Hospital of Soochow University(39 cases of prostate cancer
      with a total of 57 lesions, 45 cases of benign prostate hyperplasia) were
      examined with T(2)WI, high b-value DWI (b=1 000 s/mm(2)) and ultrahigh b-value
      DWI (b=2 000 s/mm(2)) .Three image sets were rated respectively based on PI-RADS
      V2 by two radiologists and the scores were compared with biopsy results.The
      differences of the area under the ROC curve (AUC) among the three groups of each
      observer were compared by Z test. Results: The difference of AUC between
      ultrahigh b-value DWI and T(2)WI in the diagnosis of peripheral and transitional
      zone cancer was statistically significant between the two observers (P=0.009 9,
      0.008 2, 0.010 8 and 0.004 5 respectively), and there was no significant
      difference of AUC between ultrahigh b-value DWI and high b-value DWI in the
      diagnosis of peripheral and transitional zone cancer.The inter-reader agreement
      was found to be perfect for all lesions, peripheral zone lesions and transition
      zone lesions at ultrahigh b-value DWI (kappa values were 0.738, 0.709 and 0.768
      respectively). Conclusion: The diagnostic performance of ultrahigh b-value DWI is
      superior to high b-value DWI and T(2)WI in both peripheral zone and transition
      zone cancers.

PMID- 28763885
TI  - [The diagnostic value of ultrasonic elastography and ultrasonography
      comprehensive score in cervical lesions].
AB  - Objective: To evaluate the clinical value of ultrasonic elastography and
      ultrasonography comprehensive scoring method in the diagnosis of cervical
      lesions. Methods: A total of 116 patients were selected from the Department of
      Gynecology of the first hospital affiliated with Central South University from
      March 2014 to September 2015.All of the lesions were preoperatively examined by
      Doppler Ultrasound and elastography.The elasticity score was determined by a 5
      point scoring method. Calculation of the strain ratio was based on a comparison
      of the average strain measured in the lesion with the adjacent tissue of the same
      depth, size, and shape.All these ultrasonic parameters were quantified, added,
      and arrived at ultrasonography comprehensive scores.To use surgical pathology as
      the gold standard, the sensitivity, specificity, accuracy of Doppler Ultrasound,
      elasticity score and strain ratio methods and ultrasonography comprehensive
      scoring method were comparatively analyzed. Results: (1) The sensitivity,
      specificity, and accuracy of Doppler Ultrasound in diagnosing cervical lesions
      were 82.89% (63/76), 85.0% (34/40), and 83.62% (97/116), respectively.(2) The
      sensitivity, specificity, and accuracy of the elasticity score method were 77.63%
      (59/76), 82.5% (33/40), and 79.31% (92/116), respectively; the sensitivity,
      specificity, and accuracy of the strain ratio measure method were 84.21% (64/76),
      87.5% (35/40), and 85.34% (99/116), respectively.(3) The sensitivity,
      specificity, and accuracy of ultrasonography comprehensive scoring method were
      90.79% (69/76), 92.5% (37/40), and 91.38% (106/116), respectively. Conclusion:
      (1) It was obvious that ultrasonic elastography had certain diagnostic value in
      cervical lesions. Strain ratio measurement can be more objective than elasticity
      score method.(2) The combined application of ultrasonography comprehensive
      scoring method, ultrasonic elastography and conventional sonography was more
      accurate than single parameter.

PMID- 28763886
TI  - [Application of neuroendoscope combined with minimal-access for elderly patients
      with idiopathic trigeminal neuralgia in enhanced recovery after surgery of
      microvascular decompression].
AB  - Objective: To explore the value of neuroendoscope and minimal-access in enhanced
      recovery after surgery of microvascular decompression (MVD) for treatment elderly
      patients with idiopathic trigeminal neuralgia (ITN). Methods: The clinical data
      of 62 elderly patients with ITN who undergoing neuroendoscope-assisted minimal
      access microvascular decompression were analyzed retrospectively, including
      operative data and follow-up results. Results: In 62 cases, the effective rate
      was 96.8%, with 88.7% complete cure and 8.1% little residual pain. Sixty
      successful cases were followed-up for an average of 61 months.Three cases
      recurred within 3 years after operation.Eight cases had complications after MVD.
      Conclusions: There was no serious complications that could be ascribed to old age
      and the operative result was satisfactory compared with younger age
      cases.Endoscope and minimal-access can help shorten operation time, raise the
      effectiveness of MVD, reduce postoperative recurrence rate, and enhanced recovery
      after surgery for elderly patients.

PMID- 28763887
TI  - [The diagnosis and treatment of systemic lupus erythematosus complicated with
      hydrocephalus].
AB  - Objective: To investigate the pathogenesis and management of the hydrocephalus in
      patients with systemic lupus erythematosus (SLE). Methods: Eight cases of
      hospitalized lupus patients with hydrocephalus in Peking Union Medical College
      Hospital from Jan 1990 to Mar 2017 were analyzed retrospectively.We collected the
      patients' medical records including medical history, CT and/or MRI images and
      analysis of cerebrospinal fluid via lumbar puncture in order to investigate the
      pathogenesis of the hydrocephalus in patients with SLE and summarize treatment
      experience. Results: All the 8 patients with SLE complicated with hydrocephalus
      were treated with steroids or immunosuppressive agents, and 5 cases were
      diagnosed with the central nervous system infection. Three cases received
      ventriculoperitoneal shunt, 5 cases received treatment of medicine.They all were
      followed up for 2-12 months, of which 3 cases were markedly effective, 1 case
      effective and 4 cases dead. Conclusion: The pathogenesis of lupus combined with
      hydrocephalus may have a certain relationship with the central infection, should
      take effective anti-infection treatment.We recommend cerebrospinal fluid shunt
      surgery intervention.

PMID- 28763888
TI  - [Sinus pericranii in adults: clinical features and therapeutic management (13
      cases report)].
AB  - Objective: To study the character of sinus pericranii in the adults and enhance
      the levels of the diagnosis and treatment of sinus pericranii. Methods: The
      clinical data of 13 adult patients with sinuses pericranii undergoing surgery in
      Beijing Hospital from 1992 to 2016 were analyzed retrospectively, including
      clinical manifestations, imaging data, surgical results. Results: Each of the
      patients presented with a nonpulsatile and soft tissue mass in their heads.Their
      ages ranged from 18 to 48 years (mean, 26 years). The diagnosis of the sinus
      pericranii was made by the clinical manifestations combined with CT and/or MRI
      examinations.The sinus pericranii did not play the main role in the drainage of
      the cerebral vein blood.All the patients were cured.The follow up time was from 6
      months to 20 years with no sinus pericranii recurrence in all the patients.
      Conclusions: The analysis of the drainage pattern of sinus pericranii was
      necessary before surgery in order to get a safe and good operation.The curative
      effect of the surgery on the sinus pericranii in adult was reliable.

PMID- 28763889
TI  - [Study of neuron-protective effect and mechanism of neuregulin1beta against
      cerebral ischemia reperfusion-induced injury in rats].
AB  - Objective: Thecurrent study is to explore the neuron-protective mechanism of
      neuregulin1beta (NRG1beta) in a rat model of middle cerebral artery
      occlusion/reperfusion (MCAO/R) through inhibiting the c-Jun phosphorylation.
      Methods: After 24 h of MCAO/R (referring to Longa's method), neurobehavioral
      function was measured by modified neurological severity score (mNSS) test; the
      cerebral infarction volume was detected by triphenyltetrazolium chloride (TTC)
      staining; the blood brain barrier (BBB) permeability was measured by Evans Blue
      (EB); the neuron morphology of brain tissue was observed by Nissl stain; the
      ultra-structures of the neurons were observed by transmission electron microscopy
      (TEM); the apoptotic neurons were counted by in situ cell death detection kit
      colocalized with NeuN; the expressions of phospho-c-Jun was determined by
      immunofluorescent labeling and Western blot analysis. Results: Compared with the
      sham-operation rats, the rats receiving MCAO/R showed increased mNSS (9.7+/-1.2),
      cerebral infarction volume (41.4+/-3.0)%, permeability of BBB, deformation of
      neurons, ischemia-induced apoptosis (0.63+/-0.04), and enhanced expression of
      phospho-c-Jun protein (0.90+/-0.07) (all P<0.05). Our data indicated that
      NRG1beta attenuated neurologic deficits (6.4+/-0.9), decreased the cerebral
      infarction volume (10.4+/-0.5), reduced EB extravasation (1.55+/-0.13) and the
      deformation of neurons, protected the ultra-structure of neurons, blocked
      ischemia-induced apoptosis (0.23+/-0.02), through down-regulated phospho-c-Jun
      expression (0.40+/-0.03) in MCAO/R rats (P<0.05). Conclusion: NRG1beta exerts
      neuron-protective effects against ischemia reperfusion-induced injury in rats
      through inhibiting the c-Jun phosphorylation.

PMID- 28763890
TI  - [Oncolytic property of HSV-1 recombinant viruses carrying the human IL-12].
AB  - Objective: Constructed the recombinant HSV-1 deleted ICP47 and inserted human IL
      12, and investigate the virus' replication ability and oncolytic property in
      vitro and vivo. Methods: The recombinant HSV-1 deleting ICP47 (MH1005) and then
      inserting human IL-12 (MH1006) were obtained with bacterial artificial chromosome
      technology.The replication ability and the efficiency of inhibiting tumor were
      detected in several nerve tumor cell lines infected with HSV-wt, MH1005 and
      MH1006 respectively.The murine tumor model was established by subcutaneous
      inoculation Neuro-2a cells on both sides of mice back respectively.A dosage of
      2*10(6) PFU of HSV-wt, MH1001(recombinant HSV-1 deleted IR), MH1005, MH1006 and
      Mock were injected 3 times intratumorally on one side of mice back in every 3
      days, the tumor volume and survival rate of the mice were measured. Results: The
      replication abilities of MH1005, MH1006 and HSV-wt in 293FT cells were
      insignificant (P>0.05); the replication abilities of recombinant HSV-1 in G422
      and Neuro-2a were higher than that in SK-N-SH; and the nerve tumor cells could be
      inhibited significantly by recombinant HSV-1.After 15 days of treatment, on the
      mouse backside with injection treatment, the tumor volumes of group HSV-wt (6
      267+/-484), MH1001 (5 730+/-1 071), MH1005 (4 537+/-538)and MH1006 (4 150+/
      476)mm(3) were smaller than that of group Mock (6 957+/-722) mm(3) significantly
      (all P<0.01); on the mouse backside without injection treatment, the tumor
      volumes of group MH1005 (5 952+/-607) and MH1006 (5 473+/-661) mm(3) were smaller
      than those of HSV-wt (6 785+/-1 063), MH1001 (6 774+/-808) and Mock (6 957+/-190)
      mm(3) significantly (all P<0.05); after 35 days of treatment, the mice survival
      rates of group MH1005 (100%) and MH1006 (100%) were higher than those of MH1001
      (67%), HSV-wt (50%) and Mock (33%) significantly (all P<0.05). Conclusion: MH1005
      and MH1006 can infect nerve tumor cells and replicate at high level, the viruses
      not only kill tumor cells directly but also induce immunological rejection to
      tumor, and prolong the survival of mice bearing tumor.

PMID- 28763891
TI  - [Autophagy regulated by JWA influenced sensitivity of esophageal cancer to
      cisplatin].
AB  - Objective: To explore the effect of JWA on cisplatin sensitivity and its
      potential molecular mechanism in esophageal cancer. Methods: The siRNA was used
      to inhibit the JWA expression, then cisplatin sensitivity and LC3 (autophagy
      related protein) expression levels were observed in TE1 cells.Further, the effect
      of autophagy inhibitor tamoxifen (3-MA) on above process was determined.Cisplatin
      sensitivity of 20 fresh esophageal cancer samples was evaluated by histoculture
      drug response assay (HDRA). Result: Silencing JWA gene increased the sensitivity
      of TE1 cells to cisplatin (P<0.05), and decreased the LC3-I and LC3-II proteins
      induced by cisplatin.Furthermore, combined with 3-MA increased the inhibition
      rate of cisplatin in JWA silencing group (P<0.05). Additionally, the inhibition
      rate of cisplatin on tissues with low JWA expression were higher than those with
      high expression (45.6% vs 25.6%, P=0.005). Conclusions: JWA could influence the
      cisplatin sensitivity by regulating autophagy in esophageal cancer.

PMID- 28763892
TI  - [Efficacy and safety of drainage after total knee arthroplasty].
AB  - Objective: To determine whether suction drainage is safe and effective compared
      with no-drainage in total knee arthroplasty. Methods: The literature search was
      based on PubMed, MEDLINE, EMBASE, Highwire, the Cochrane Library, CBM, CNKI, VIP
      and WFSD.The data were analysed using RevMan 5.3.Fourteen randomised controlled
      trials involving 1 009 knees were included in our analysis. Results: Suction
      drainage increases the rate and volume of blood transfusion.No-drainage group
      increases the rate of wound problems (OR=1.92, 95%CI 1.21-3.04, P<0.05). No
      significant difference was observed in the incidence of periprosthetic infection
      (OR=0.68, 95%CI 0.20-2.30, P=0.54), VAS (OR=-0.09, 95%CI -0.32-0.14, P=0.46) and
      the length of stay (OR=0.41, 95%CI -0.21-1.03; P=0.19) when the drainage group
      was compared with the no-drainage group (P>0.05). Conclusions: No-drainage for
      easy total knee arthroplasty may be a better choice. However, orthopedic surgeon
      need to weigh the pros and cons of no-drainage in some complicated TKAs such as
      extra-articular deformity .

PMID- 28763893
TI  - [Pay close attention to fulminant type 1 diabetes].

PMID- 28763894
TI  - [Cardiovascular benefits and underlying mechanisms of GLP-1 receptor agonists in
      patients with type 2 diabetes].

PMID- 28763895
TI  - [Utility of hemoglobin A1c for diagnosing metabolic syndrome in Chinese subjects
      over 50 years old].
AB  - Objective: To evaluate glycated hemoglobing A1c (HbA1c) in diagnosing metabolic
      syndrome (MS) in Chinese subjects aged over 50 years. Methods: A community-based
      cross-sectional survey was conducted between October 2010 and January 2011 in
      Shipai community, Guangzhou. A total of 1 494 subjects aged over 50 years were
      investigated. Questionnaire survey and physical examination were performed among
      all participants. Fasting blood samples were obtained to measure plasma glucose
      (FPG), blood lipids and HbA1c. MS was defined by the criteria of International
      Diabetes Federation (IDF), National Cholesterol Education Program-Adult Treatment
      Panel III (ATP III)(2005) and Chinese Diabetes Society (CDS), respectively.
      Receiver operating characteristic (ROC) curves were plotted to explore the
      accuracy of HbA1c for diagnosing MS. Results: After excluding subjects with
      missing data, the remaining 1 473 subjects had a median age of 61 years (55-68
      years). An HbA1c threshold of 6.1% yielded the highest combination of sensitivity
      (52.1%) and specificity (84.3%) for diagnosing MS. Using HbA1c>=5.7% as
      definition of dysglycemia, the prevalence of MS (IDF), MS (ATP III) and MS (CDS)
      were 48.7%, 57.1% and 50.8%, respectively. The kappa coefficients were 0.853,
      0.768 and 0.730, respectively. Using HbA1c>=6.1% as definition of dysglycemia,
      the prevalences of MS (IDF), MS (ATP III) and MS (CDS) were 41.2%, 45.8% and
      39.1%, respectively. The kappa coefficients were 0.923, 0.880 and 0.881,
      respectively. The optimal HbA1c threshold with the highest level of agreement
      according to IDF, ATP III and CDS criteria were 6.1%, 6.3% and 6.3%,
      respectively. Conclusions: An HbA1c threshold of 6.1% showed a high specificity
      for diagnosing MS in Chinese subjects aged over 50 years in community-based
      setting. The optimal HbA1c threshold may vary according to different criteria and
      populations.

PMID- 28763896
TI  - [Association between serum uric acid levels and high sensitive C-reactive protein
      in patients with type 2 diabetes].
AB  - Objective: To investigate the relationship between serum uric acid (SUA) levels
      and high sensitive C-reactive protein (hs-CRP) in patients with type 2 diabetes
      mellitus (T2DM). Methods: A total of 400 patients who were hospitalized in the
      Department of Endocrinology and Metabolism of Jinshan Branch, Shanghai Sixth
      People's Hospital between April 2014 and December 2015 were divided into
      normouricemia (NUA, n=319) group and hyperuricemia (HUA, n=81) group according to
      the presence of HUA. Clinical features of the two groups were compared. Patients
      were further stratified into quartiles based on SUA levels, and then association
      between hs-CRP and SUA was analyzed. Results: Compared to the NUA group, the
      patients with HUA had higher hs-CRP concentration [2.12 (1.15, 6.73) mg/L vs 1.14
      (0.52, 3.44) mg/L, P<0.001], erythrocyte sedimentation rate (ESR) [19.0 (10.5,
      29.5) mm/h vs 12.0 (8.0, 17.0) mm/h, P<0.001], body mass index (BMI) [(25.2+/
      3.6) kg/m(2) vs (23.6+/-3.6) kg/m(2,) P<0.001], and homeostasis model assessment
      2 of insulin resistance (HOMA2-IR) index [1.88 (1.11, 2.94) vs 1.27 (0.77, 2.00),
      P<0.001]. After adjusting for age, the median level of hs-CRP of female with HUA
      was higher than that of male, female with NUA, and male with NUA (2.59, 1.94,
      1.25 and 1.09 mg/L, respectively, P<0.001). There was significant difference in
      the prevalence of HUA among the patients with underweight, normal weight,
      overweight, and obesity (0, 12.3%, 21.6% and 25.8%, respectively, P=0.002). After
      adjusting for age and gender, duration of diabetes, BMI, serum lipids, level of
      SUA was still correlated with hs-CRP, HOMA2-IR, fasting C-peptide, blood urea
      nitrogen, serum creatinine, Cystatin C, microalbuminuria, respectively(all
      P<0.05). The level of SUA was positively associated with the increase of hs-CRP
      level (P=0.001). Multiple linear regression analysis showed that there was an
      independent and positive association between SUA and hs-CRP levels. Conclusion:
      SUA was independently associated with hs-CRP in T2DM patients, which suggested
      that chronic inflammation exists in HUA patients.

PMID- 28763897
TI  - [Effect of Alloxan-induced diabetes mellitus on the functions of bone marrow
      derived and circulating endothelial progenitor cells].
AB  - Objective: To explore whether diabetes mellitus (DM) impairs functions of bone
      marrow-derived endothelial progenitor cells (BM-EPC) and circulating EPC.
      Methods: Diabetic model of rabbit was induced by Alloxan injection and the
      rabbits were then randomly divided into three groups: BM-EPC group, circulating
      EPC group, and DM group, with six rabbits in each group. Another 6 normal rabbits
      were enrolled as normal control group as well. 8 weeks later, BM-EPC and
      circulating EPC from diabetic and healthy rabbits were isolated and cultured.
      Colony number, proliferation, adhesion and tube formation function were detected.
      Exogenous diabetic BM-EPC and circulating EPC were analyzed for therapeutic
      efficacy in acute ischemia model of diabetic rabbits. Left ventricular (LV)
      function was assessed using Echocardiography. Capillary density and fibrosis area
      were evaluated by confocal laser scanning microscope (CLSM) and Masson-trichrome
      staining. The mRNA expression of vascular endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF) was analyzed using real-time quantitive
      PCR. Results: Colony number, proliferation, adhesion and tube formation function
      of diabetic circulating EPC were significantly reduced compared with healthy
      rabbits. DM impaired tube-forming ability of BM-EPC, but did not influence colony
      number, proliferation and adhesion function. Compared with circulating EPC and
      control group, BM-EPC group had fewer fibrosis area (6.98%+/-0.94% vs 13.03%+/
      2.97% and 15.84%+/-4.74%, both P=0.001), higher capillary density [(792+/-87) vs
      (528+/-71) and (372+/-77) vessels/mm(2,) both P<0.001], higher mRNA expression of
      VEGF (6.25+/-2.33 vs 2.19+/-1.01 and 1.55+/-0.52, both P<0.001) and bFGF (6.38+/
      2.65 vs 1.24+/-0.76 and 1.18+/-0.82, both P<0.001), higher left ventricular
      ejection fraction (LVEF) (61%+/-4% vs 47%+/-5% and 50%+/-10%, both P<0.05).
      Conclusions: DM not only impaired functions of circulating EPC, but also
      influenced tube formation function of BM-EPC. Auto transplantation of BM-EPC may
      rescue the ischemic myocardium by neovascularization and paracrine effect in
      diabetic rabbits.

PMID- 28763898
TI  - [Effect of single lumen endobronchial tube and double lumen endobronchial tube on
      ventilation and lung injury in patients with esophageal cancer undergoing
      combined thoracoscopic and laparoscopic esophagectomy].
AB  - Objective: To investigate the effect of the single lumen endobronchial tube and
      the double lumen endobronchial tube on ventilation and lung injury in patients
      with esophageal cancer undergoing combined thoracoscopic and laparoscopic
      esophagectomy. Methods: Sixty patients with esophageal cancer undergoing combined
      thoracoscopic and laparoscopic esophagectomy were divided into single lumen
      endobronchial tube group (D group, n=30) and double lumen endobronchial tube
      group (S, n=30) according to the random number table. Blood samples were
      harvested at the moment of tracheal intubation (T(0)), after artificial
      pneumothorax (one lung ventilation) 30 min (T(1)), after artificial pneumothorax
      (one lung ventilation) 90 min (T(2)), artificial pneumothorax over (double lung
      ventilation) 30 min (T(3)) and after extubation 30 min (T(4)) for arterial blood
      gas analysis. Heart rate (HR), mean arterial pressure (MAP), pulse oxygen
      saturation (SpO(2)), oxygen tension (PaO(2)), carbon dioxide partial pressure
      (PaCO(2)) and airway pressure (PAW) were recorded at T(0)-T(4). The incidences of
      pneumonia of two groups were record at 3 days after operation. Results: There
      were no obvious differences in HR, MAP, SpO(2), PaO(2), PaCO(2) between two
      groups at T(0)-T(4) (P>0.05). Compared with T(0), the levels of HR and PaO(2)
      were increased remarkably at T(1)-T(3) (P<0.05), the levels of PaCO(2) were
      increased remarkably at T(1)-T(4) (P<0.01), and the levels of Paw were increased
      remarkably at T(1)-T(3) (P<0.01). Compared with S group, the levels of Paw were
      decreased remarkably at T(1)-T(2) (29.5+/-3.7 vs 21.3+/-2.1, P=0.001; 30.7+/-4.8
      vs 20.3+/-2.3, P=0.001). There were no obvious differences in the levels of TNF
      alpha, IL-6, IL-8 in Bronchoalveolar Lavage Fluid (BALF) between two groups at
      T(0) (P>0.05). Compared with T(0), the levels of TNF-alpha, IL-6, IL-8 in BALF
      were increased remarkably at T(3), T(5) (P<0.05). Compared with S group, the
      levels of TNF-alpha, IL-6, IL-8 in D group in BALF were decreased remarkably at
      T(3), T(5) (P<0.05). Compared with S group, the incidence of pneumonia in D group
      were decreased remarkably at 3 days after operation (4(13.3%) vs 11(36.7%),
      P=0.017). Conclusion: The ventilation effect of the single lumen endobronchial
      tube on lung injury for patients with esophageal cancer undergoing combined
      thoracoscopic and laparoscopic esophagectomy is the same as that of the double
      lumen endobronchial tube, however the single lumen endobronchial tube has less
      injury on the lung.

PMID- 28763899
TI  - [Impact of antifungal therapy in mechanically ventilated patients with Candida
      spp. colonization in lower respiratory tract].
AB  - Objective: To explore the impact of antifungal therapy in mechanically ventilated
      patients with Candida spp. colonization in lower respiratory tract. Methods: In
      this retrospective study, patients required mechanical ventilation with pulmonary
      Candida spp. colonization admitted into the intensive care unit (ICU) between
      July 2012 and June 2016 were included. The patients were divided into the
      treatment group and control group according to whether or not they received
      antifungal therapy. The isolation rate of multidrug-resistant (MDR) bacteria, the
      incidence of ventilator-associated pneumonia (VAP), duration of mechanical
      ventilation, length of ICU stay, total length of hospital stay, the 28-day
      mortality and the overall mortality were compared between the two groups.
      Results: Totally, 101 patients were studied. The number of cases in treatment
      group was 56 and the control group was 45. The treatment group had a lower
      incidence of MDR bacteria isolation rate and VAP compared with the control group
      (16.1% vs 33.3%, 5.4% vs 17.8% respectively, both P<0.05). There were significant
      differences in the duration of mechanical ventilation [(17.3+/-5.7) days vs
      (22.5+/-7.2) days, P<0.05], length of ICU stay [(23.3+/-5.6) days vs (28.7 +/
      4.8) days, P<0.05] and the average length of hospital stay [(36.2+/-8.7) days vs
      (43.6+/-9.0) days, P<0.05)] in the treatment group compared with the control
      group. There were no statistical difference between the two groups in the 28-day
      mortality and the overall mortality. Conclusion: Treatment of respiratory Candida
      spp. colonization in mechanically ventilated patients may reduce isolation rate
      of MDR bacteria, the incidence of VAP, duration of mechanical ventilation, length
      of ICU stay and total length of hospital stay.

PMID- 28763900
TI  - [Application of mini-flank open nephron sparing surgery via retroperitoneal route
      for centrally located renal tumor treatment: a single center experience].
AB  - Objective: To investigate the safety and feasibility of mini-flank open nephron
      sparing surgery (MI-OPN) via retroperitoneal route for the treatment of centrally
      located renal tumor. Methods: From May 2013 to April 2015, twenty-four cases of
      centrally located renal tumor were treated with MI-OPN via retroperitoneal route
      in Zhongshan Hospital. All cases were included in this study with whose clinical
      data and long term follow-up information retrospectively analyzed. Results: With
      the assistance of intraoperative ultrasonography to confirm tumor location and
      boundary, MI-OPN was successfully performed in all cases. Mean tumor maximum
      diameter was 3.3+/-0.6 cm, mean operation time was 113+/-16 minutes, mean
      ischemia time was 31+/-6 min, and mean estimated blood loss was 102+/-46 ml. Mean
      postoperative hospital stay was 5.0+/-0.8 days, postoperative complication was
      found in one patient (4%). The mean pre- and postoperative serum creatinine were
      77.1+/-20.1 MUmol/L and 90.3+/-20.0 MUmol/L. Pathological examination confirmed
      negative surgical margin in all cases, with 18 cases of clear cell renal cell
      carcinoma, 2 cases of papillary renal cell carcinoma, 2 cases of chromophobe
      renal carcinoma, 1 case of renal oncocytoma and 1 case of renal angiomyolipoma.
      In up to 12-36 months postoperative follow-up, no local recurrence or systemic
      progression was witnessed. Conclusions: For the treatment of centrally localized
      renal tumor, MI-OPN via retroperitoneal route is a safe and feasible operation
      method. Importantly, rupture of the tumor capsule was effectively avoided during
      tumor resection with the assistance of ultrasonic position-setting. Furthermore,
      incidence of severe postoperative complications such as bleeding and damage of
      collection system were not found since surgical wound of kidney sewn tightly and
      finely. The last but not the least, by placing ice slush in retroperitoneal
      cavity, impairment of renal function caused by renal artery clamping can be
      alleviated due to decreased metabolism.

PMID- 28763901
TI  - [Diagnosis and treatment experience of transurethral resection for paraganglioma
      of urinary bladder in 8 cases].
AB  - Objective: To discuss the experience of diagnosis and treatment of transurethral
      resection of paraganglioma in urinary bladder. Methods: This retrospective study
      included 8 patients who underwent transurethral resection of paraganglioma in
      bladder from October 2009 to April 2015. Four males and 4 females were enrolled.
      The age ranged from 33 to 77 years (mean: 50.4 years), with a clinical course
      from 1 month to 8 years. Five cases presented with hypertension and 4 had high
      level of noradrenaline in blood. Preoperative ultrasound, CT and MRI were
      performed on every patient and the results showed all tumors were solitary and
      limited in bladder wall. Six patients received conventional transurethral
      electroresection and the other 2 patients received transurethral resection with
      thulium laser.Postoperative follow-up of each case was recorded. Results: All
      tumors were excised successfully without converting to open surgery. The maximum
      diameter of tumors ranged from 1.0 to 4.5 cm (mean: 2.3 cm), operative time
      varied from 15 to 35 min (mean: 28.1 min) and intraoperative blood loss ranged
      from 20 to 50 ml (mean: 31.9 ml). The variation of blood pressure during
      operation was 10 to 160 mmHg (mean: 66.3 mmHg). The loss of follow-up occurred in
      1 case, tumor recurrence occurred in 1 case at 3 months after surgery and the
      follow-up data of other patients was normal. Conclusions: The diagnosis of
      paraganglioma in bladder should be combined with clinical symptoms, biochemical
      and imaging examination for some cases. Transurethral resection of tumors is a
      safe and reliable surgical manner.

PMID- 28763902
TI  - [Role of Yes-associated protein 1 in angiotensinII-induced pulmonary fibrosis in
      rats].
AB  - Objective: To explore the mechanism of Yes-associated protein 1 (Yap1) in
      angiotensinII(AngII)-induced pulmonary fibrosis. Methods:In vivo, 18 male Wistar
      rats were randomly divided into three equal groups with 6 rats in each group,
      including control group, bleomycin-treated group (BLM), and BLM+ AngII group. 28
      days later, the lung tissues in all groups were harvested for the HE and Masson
      staining as well as the immunohistochemical (IHC) staining for Yap1. In vitro,
      the isolated fibroblasts were treated with 10(-7) mmol/L AngIIor the AngII
      targeted inhibitor irbesartan for the scheduled time for mRNA and protein
      expressions of Yap1, PDZ-binding motif (TAZ), and collagen Iusing PCR and Western
      blot, as well as the translocation test from the nucleus to the cytoplasm of Yap1
      and TAZ. Subsequently, the fibroblasts were assigned into 4 groups: the empty
      plasmid (vector) group, the vector+ AngII group, the Yap1 shRNA group, and the
      Yap1 shRNA+ AngII group. Western blot was used to detect the relative expressions
      of Yap1, TAZ, Smad3 and collagen I. The CCK-8 and EdU assays were performed to
      determine the proliferative capacity. Results:In vivo, severe lung fibrosis and
      increased Yap1 expression of IHC staining were found in BLM group. Additionally,
      more severe lung fibrosis and higher Yap1 expression were detected in the BLM+
      AngII group than the BLM group (both P<0.05). In vitro, both the mRNA and protein
      relative expressions of Yap1, TAZ and collagenI were markedly higher in AngII
      treated groups than the control group (all P<0.05). Meanwhile, the relative
      expression of phosphorylated Yap1 reached its peak at 2 h after AngII
      stimulation. In the protein translocation tests, after treated with AngII for 24
      h, the relative protein levels of Yap1 and TAZ in the nucleus of the AngII group
      were significantly higher than those in the control group (0.382+/-0.007 vs
      0.031+/-0.001, 1.097+/-0.030 vs 0.357+/-0.015). However, the relative protein
      expressions in the cytoplasm of the AngII group were obviously less than that in
      the control group (0.323+/-0.058 vs 0.418+/-0.044, 0.858+/-0.059 vs 1.201+/
      0.015). Compared with the AngII group, the expressions of Yap1 and TAZ in the
      AngII+ irbesartan group were higher in cytoplasm (0.598+/-0.060 vs 0.323+/-0.058,
      1.495+/-0.052 vs 0.858+/-0.059), while lower in the nucleus (0.323+/-0.058 vs
      0.418+/-0.044, 0.858+/-0.059 vs 1.201+/-0.015) (all P<0.05). Furthermore, the
      relative protein expressions of Yap1, TAZ, Smad3 and collagenIin Yap1 shRNA+
      AngII group were distinctly lower than the vector+ AngII group (all P<0.05). In
      the cell proliferation tests, the absorbance and the percentage of EdU positive
      cells of vector+ AngII group exceeded that of vector group (both P<0.05).
      However, the absorbance and the percentage of EdU positive cells in the Yap1
      shRNA+ AngIIgroup were less than the vector+ AngII group (both P<0.05).
      Conclusion: AngiotensinII promoted the collagen synthesis and cell proliferation
      in primary lung fibroblasts by increasing the Yap1 activity, leading to the
      progress of fibrosis.

PMID- 28763903
TI  - [Role of roxithromycin on glucocorticoid resistance of human bronchial epithelial
      cells and its mechanism].
AB  - Objective: To explore the effects of roxithromycin (RXM) on glucocorticoid
      resistance of human bronchial epithelial cells exposed to smoke and its
      mechanism. Methods: Beas-2B cells as the research object were grouped into:
      control group, 10%cigarette smoke extract (CSE) group, roxithromycin (RXM)+
      10%CSE group. With 10%CSE intervention in the 10%CSE group, 10%CSE and RXM
      intervention in the RXM+ 10%CSE group, complete culture solution intervention in
      the control group. Interleukin-8 (IL-8) levels were measured by enzyme linked
      immunosorbent assay (ELISA) and IL-8 inhibition rate and dexamethasone half
      inhibitory concentration (IC50-Dex) were calculated; the expression of histone
      deacetylase 2 (HDAC2) protein was detected by immunofluorescence (IF) and Western
      blotting (WB). Results: In response to dexamethasone at the concentration of 10(
      9,) 10(-8,) 10(-7) and 10(-6) mol/L successively, the IL-8 inhibition rates of
      RXM+ 10%CSE group [(27.55+/-3.81)%, (49.60+/-1.45)%, (55.36+/-3.36)%, (60.32+/
      3.13)%, respectively] were lower than those of control group [(32.85+/-2.56)%,
      (57.12+/-2.81)%, (60.81+/-2.08)%, (67.24+/-3.50)%, respectively], but higher than
      those of 10%CSE group [(19.15+/-1.69)%, (37.02+/-2.30)%, (47.15+/-2.01)%,
      (52.09+/-1.57)%, respectively] (all P<0.05). In contrast, the IC50-Dex of RXM+
      10%CSE group [(4.94+/-1.62)*10(-8)] was significantly higher than that of control
      group [(1.75+/-0.77)*10(-8)], but lower than that of 10%CSE group [(2.92+/
      0.78)*10(-7)] (both P<0.01). The expression of HDAC2 protein of 10%CSE group
      (0.011+/-0.004 from IF and 0.46+/-0.10 from WB) was lower than that of control
      group (0.037+/-0.005 and 0.91+/-0.06, correspondingly), while RXM+ 10%CSE group
      (0.025+/-0.005 and 0.77+/-0.09, correspondingly) was lower than that of control
      group but higher than that of 10%CSE group (all P<0.05). Conclusion:
      Roxithromycin may restrain tobacco smoke exposure-induced glucocorticoid
      resistance in human bronchial epithelial cells through upregulating HDAC2
      expression.

PMID- 28763904
TI  - [Discussion on the related problems of pediatric burn treatment].
AB  - The incidence of pediatric burn is high currently. Many clinical problems in the
      treatment of pediatric burn are composed of fluid replacement during shock stage,
      wound treatment, nutrition and metabolism etc, which urgently need to be sorted
      out and updated again to make corresponding clinical guidelines, criteria, or
      consensus for standardizing the clinical diagnosis and treatment, so as to
      improve the clinical treatment level of pediatric burn.

PMID- 28763905
TI  - [Analysis of drug resistance of Acinetobacter baumannii in wound of children with
      traffic injury and its relationship with antibiotic use].
AB  - Objective: To know the drug resistance of Acinetobacter baumannii (AB) in wound
      of children with traffic injury and its relationship with antibiotic use.
      Methods: Wound exudate of 226 children with traffic injury admitted to our unit
      from January 2010 to December 2015 were collected. API bacteria identification
      panels and fully automatic microbiological identification system were used to
      identify pathogens. Kirby-Bauer paper disk diffusion method was used to detect
      the drug resistance of pathogens to 18 antibiotics including
      amoxycillin/clavulanic acid, piperacillin/tazobactam, and imipenem. The detection
      situation of pathogen of children's wounds and drug resistance of detected AB to
      18 antibiotics in each year were collected. Forty-six AB positive children (2
      children excluded) were divided into imipenem-resistant group (IR, n=19) and non
      imipenem-resistant group (NIR, n=25) according to whether AB was 100% resistant
      to imipenem. Drug resistance of AB in wounds of children to 18 antibiotics in two
      groups was compared. The antibiotic use of AB positive children was collected,
      and the antibiotic use intensity of children in two groups was compared. Data
      were processed with Fisher's exact test, independent sample t test, and corrected
      t test. Results: (1) The detection rates of pathogen in wounds of children in
      2010-2015 were 95.6% (43/45), 89.8% (53/59), 81.3% (148/182), 81.1% (107/132),
      81.6% (120/147), and 77.5% (62/80), respectively, showing a trend of decreasing
      year by year. A total of 665 strains and 75 pathogens were detected, and the top
      5 pathogens with detection rate from high to low were AB, Pseudomonas aeruginosa,
      Enterobacter cloacae, Staphylococcus epidermidis, and Escherichia coli,
      respectively. (2) Drug resistance rates of AB to amoxycillin/clavulanic acid,
      cefazolin, aztreonam, and piperacillin were all 100%, while AB was 100% sensitive
      to polymyxin, and the total drug resistance rates of AB to the other 13
      antibiotics were all above 50%. The drug resistance rate of AB in wounds of
      children to piperacillin was higher than that to piperacillin/tazobactam in 2010
      2015. (3) Except for imipenem, amoxycillin/clavulanic acid, cefazolin, aztreonam,
      piperacillin, and polymyxin, the drug resistance rates of AB in wounds of
      children in group IR to the other 12 antibiotics were higher than those in group
      NIR (with P values below 0.01). Besides, AB strains in wounds of children in
      group IR were completely resistant to at least 3 kinds of antibiotics including
      carbapenems, aminoglycosides, and quinolones, so that they were multidrug
      resistant AB. (4) A total of 32 antibiotics were used in 46 AB positive children,
      and the 10-top-used antibiotics with use intensity from high to low were
      cefoperazone/sulbactam, piperacillin/tazobactam, cefazolin, imipenem,
      ceftizoxime, amoxycillin/clavulanate, ceftazidime, cefepime,
      amoxycillin/sulbactam, and cefmetazole, respectively. (5) Twenty-one antibiotics
      were not included in the comparison because of their small amount of usage. For
      the other 11 antibiotics, only the use intensity of metronidazole of children in
      two groups was statistically different (t=-3.104, P<0.05). There was no
      statistically significant difference in total antibiotic use of children in two
      groups (t=0.368, P>0.05). Conclusions: AB is one of the main pathogens in wounds
      of children with traffic injury, with high drug resistant rate. The high
      intensity of antibiotic use may lead to its drug resistance. In this study, the
      top-used antibiotics were in accord with AB resistant drugs, indicating a lack of
      normative use of antibiotics.

PMID- 28763906
TI  - [Effects of scar excision combined with negative-pressure on repair of
      hypertrophic scar in burn children].
AB  - Objective: To explore the effects of scar excision combined with negative
      pressure on repair of hypertrophic scar in burn children. Methods: From October
      2010 to August 2016, 25 children with hypertrophic scar after deep burn were
      hospitalized, with scar course ranging from 3 months to 11 years and scar area
      ranging from 35 to 427 [83(51, 98)]cm(2). A total of 35 scars of 25 children were
      located in trunk (11 scars), upper limb (11 scars), and lower limb (13 scars).
      All children received scar excision operation and negative-pressure treatment
      (negative-pressure value ranged from -40 to -20 kPa), among which 6 cases
      received scar excision operation and negative-pressure treatment for two times
      for further removal of scars. After scar excision, electronic spring scale was
      used to measure the tension of the incision. The tension value of children ranged
      from 3.43 to 23.84 [7.16 (5.59, 9.12)] N, and then the incision was closed with
      appropriate suture according to the value of the tension. The incision with
      smaller tension was firstly opened on post operation day (POD) 8. After removing
      the suture, negative-pressure was conducted to POD 14. The incision with larger
      tension was firstly opened on POD 12. After removing the suture, biological semi
      membrane was used to reduce tension to POD 16. All healed incisions were
      performed with anti-scar treatment for 1 year and relaxation and fixation for 3
      months. General condition of the incision was observed after operation. The
      reduction percentage of scar area was calculated half-year after operation. The
      Patient and Observer Scar Assessment Scale was used to record the overall score
      of scar and scar score of trunk, upper limb, and lower limb before operation and
      half-year after operation. Data were processed with paired t test and Wilcoxon
      rank sum test. Results: After removing the suture, all incisions of children
      healed well without redness, effusion, and rupture. Half-year after operation,
      the appearance and deformity of incision were obviously improved, and the
      symptoms including pruritus and pain were basically relieved. Half-year after
      operation, the scar area of children ranged from 0 to 174 [21(9, 47)]cm(2,) which
      was significantly decreased as compared with that before operation (Z=-5.16,
      P<0.05). The reduction percentage of scar area ranged from 36% to 100% [(73+/
      19)%]. Half-year after operation, the overall score of scar and scar score of
      trunk, upper limb, and lower limb of children were obviously decreased as
      compared with those before operation (with t values from 6.42 to 17.37, P values
      below 0.05). Conclusions: Scar excision combined with negative-pressure treatment
      has a good clinical effect on repair of hypertrophic scar in burn children, which
      is suitable for clinical application.

PMID- 28763907
TI  - [Epidemiological investigation of hospitalized children with burn injury in a
      hospital of Qingdao].
AB  - Objective: To investigate epidemiological characteristics of hospitalized
      children with burn injury in the author's affiliation, so as to provide
      theoretical basis for developing prevention strategies of children with burn
      injury. Methods: Medical records of 384 and 596 hospitalized children with burn
      injury, aged 0 to 12-year-old, were collected respectively from January 2001 to
      December 2005 and January 2011 to December 2015. Percentage of children with burn
      injury to total hospitalized patients with burn injury in the same period of
      time, age, causes of injury, gender, injury month, residence, condition of first
      aid measures conforming to medical standard, time of admission post injury, burn
      degree, and operation condition of children with burn injury were analyzed. Data
      were processed with Mann-Whitney U test and Chi-square test. Results: From
      January 2001 to December 2005 and January 2011 to December 2015, percentages of
      children with burn injury to total hospitalized patients with burn injury in the
      same period of time were respectively 23.6% (384/1 626) and 25.4% (596/2 346) ,
      with no statistically significant difference (chi(2)=1.653, P>0.05). Age of all
      children with burn injury was 1.0 (1.0, 2.0) year old from January 2011 to
      December 2015, obviously lower than that from January 2001 to December 2005[1.0
      (1.0, 3.0) year old, Z=-3.257, P<0.01]. Ages of children with burn caused by hot
      liquid and electrical burn from January 2011 to December 2015 were obviously
      lower than those from January 2001 to December 2005 (with Z values respectively 
      4.248 and -2.040, P<0.05 or P<0.01). Compared with that from January 2001 to
      December 2005, age of children with burn caused by flame from January 2011 to
      December 2015 increased, with no statistically significant difference (Z=1.852,
      P>0.05). There was no statistically significant difference in gender of children
      with burn injury between the two periods of time (chi(2)=1.374, P>0.05). Burn
      injury of children in the two periods of time mainly occurred in Spring, and
      season of burn injury between the two periods of time was similar (chi(2)=1.177,
      P>0.05). There was statistically significant difference in residence of children
      with burn injury between the two periods of time (chi(2)=15.513, P<0.01). The
      number of children with burn injury of first aid measures conforming to medical
      standard and admission within 6 h post injury from January 2011 to December 2015
      was obviously more than that from January 2001 to December 2005 (with chi(2)
      values respectively 7.434 and 43.961, P values below 0.01). Burn degrees of
      children with burn injury mainly were moderate in the two periods of time, and
      there was no statistically significant difference in burn degree and condition of
      operation between the two periods of time (with chi(2) values respectively 5.731
      and 1.583, P values above 0.05). Conclusions: Burn of children is a social
      problem. We should make great efforts on popularization of prevention and
      treatment about burn of children, especially children with younger age in rural
      areas. We should publicize standard first aid measures of burn of children and
      advocate admission of burn of children within 6 h post burn injury for treatment.

PMID- 28763908
TI  - [Effects of flow-through descending branch of lateral circumflex femoral artery
      flap on repairing high-voltage electrical burn wounds of wrist of patients].
AB  - Objective: To investigate the effects of flow-through descending branch of
      lateral circumflex femoral artery flap on repairing high-voltage electrical burn
      wounds of wrist of patients. Methods: From January 2014 to June 2016, 5 patients
      with high-voltage electrical burn of unilateral wrist were hospitalized in our
      burn ward, with extensive necrosis of skin soft tissue of burn wrist. Five
      patients were transferred to our burn ward 6 to 12 days post injury after
      undergoing emergency dermotomy of wrist to reduce tension in other hospitals. In
      2 to 3 days after admission, operation was performed by two surgeon group at the
      same time, when patients' general condition were stable. One group underwent
      debridement and the other group designed and dissected flap according to the
      range of skin soft tissue defect of wrist. Wrist wounds after debridement ranged
      from 15 cm*10 cm to 24 cm*15 cm. Three patients were treated with flow-through
      descending branch of lateral circumflex femoral artery flap and great saphenous
      vein for repairing wounds of wrist and reconstruction of ulnar and radial artery.
      Two patients were treated with flow-through descending branch of lateral
      circumflex femoral artery flap for repairing wounds of wrist and reconstruction
      of ulnar artery. The dissected flaps ranged from 16 cm*12 cm to 26 cm*16 cm and
      the length of bridging vessel ranged from 15 to 21 cm. Results: The flow-through
      descending branch of lateral circumflex femoral artery flaps of five patients
      survived well. Wounds of 4 patients healed and wounds of 1 patient with infection
      under the flap on 3 days after operation healed after changing wound dressing and
      undergoing debridement for 2 weeks. After the operation, wrists and hands of 5
      patients had adequate blood supply and ulnar and radial artery recovered patency.
      Follow-up of patients for 6 months to 1 year showed good flap appearance and
      adequate blood supply of burn hands. Conclusions: The flow-through descending
      branch of lateral circumflex femoral artery flap can repair wrist wounds and
      recover blood supply of hands and it is a good method for repairing high-voltage
      electrical burns of wrist.

PMID- 28763909
TI  - [Effects of functional training combined with self-made hand flexing training
      band in treatment of scar contracture after burn injury of dorsal hand].
AB  - Objective: To observe the effects of functional training combined with self-made
      hand flexing training band in treatment of scar contracture after burn injury of
      dorsal hand. Methods: Forty-six patients with scar contracture after deep partial
      thickness or full-thickness burn injury of dorsal hand hospitalized in our
      department from March 2013 to February 2015 were divided into routine training
      group (RT, n=18) and comprehensive training group (CT, n=28) according to their
      willingness. Two weeks after the wounds were healed, patients in group RT were
      treated with functional training of hands and self-made pressure gloves, while
      patients in group CT were treated with self-made hand flexing training band
      (consisting of nylon strap, flexing band, and velcro) on the basis of those in
      group RT. All patients were treated for 3 months. Before and after treatment,
      scar condition of affected hands was assessed with Vancouver Scar Scale (VSS).
      The range of motion of joints of affected hands was measured by Total Active
      Movement (TAM) Scale. The function of affected hands was evaluated by Carroll
      Upper Extremity Function Test. Data were processed with t test, chi-square test,
      and Mann-Whitney U test. Results: (1) The score of VSS in patients of group RT
      was (10.0+/-1.9) points before treatment and (4.4+/-1.4) points after treatment,
      with the improved score of (5.6+/-1.0) points. The score of VSS in patients of
      group CT was (10.5+/-1.8) points before treatment and (4.6+/-1.4) points after
      treatment, with the improved score of (5.9+/-1.2) points. There was no
      statistically significant difference in the improved score of patients between
      the two groups (t=0.834, P>0.05). The score of VSS in patients of groups RT and
      CT after treatment was significantly lower than that before treatment (with t
      values respectively 14.014 and 10.003, P values below 0.01). (2) Before
      treatment, the ratios of excellent and good results according to TAM were 2/9 in
      patients of group RT and 3/14 in group CT, with no statistical differences
      between them (chi(2)=2.140, P>0.05). After treatment, the ratio of excellent and
      good results according to TAM in patients of group CT (6/7) was higher than that
      in group RT (5/9, chi(2)=0.023, P=0.038). The ratios of excellent and good
      results according to TAM in patients of groups RT and CT after treatment were
      significantly higher than those before treatment (with Z values respectively 
      2.023 and -4.780, P values below 0.05). (3) The improved score of hand function
      in patients of group CT was (26+/-12) points, which was higher than (15+/-7)
      points in group RT (t=3.278, P=0.002). The score of hand function in patients of
      groups RT and CT after treatment was significantly higher than that before
      treatment (with t values respectively 2.628 and 6.125, P values below 0.05).
      There were no significant differences in grades of hand function of patients
      between the two groups before treatment (Z=-0.286, P>0.05). After treatment, the
      grade of hand function in patients of group CT was higher than that in group
      RT(Z=-1.993, P=0.046). The grades of hand function in patients of groups RT and
      CT after treatment were significantly higher than those before treatment (with Z
      values respectively -2.717 and -4.998, P values below 0.01). Conclusions: For
      patients with scar contracture after burn injury of dorsal hand, early functional
      training combined with hand flexing training band can improve the range of motion
      of hand joints and functional recovery of hand, and the result was better than
      functional training alone.

PMID- 28763911
TI  - [Cancer comprehensive prevention and control under the new era].

PMID- 28763910
TI  - [Influence of different inner dressings in negative-pressure wound therapy on
      escharectomy wound of full-thickness burn rabbits].
AB  - Objective: To explore the influence of different inner dressings in negative
      pressure wound therapy (NPWT) on escharectomy wound of full-thickness burn
      rabbits. Methods: Eighteen Japanese white rabbits were inflicted with full
      thickness burn on unilateral back. They were divided into polymer dressing group
      (PD), biological dressing group (BD), and silver biological dressing group (SBD),
      according to the random number table, with 6 rabbits in each group. On 3 days
      post burn, the wounds were performed with escharectomy, and then wounds of
      rabbits in group PD were covered with polyurethane foam. Wounds of rabbits in
      group BD were covered with porcine acellular dermal matrix (ADM) and wounds of
      rabbits in group SBD were covered with silver porcine ADM. Then continuous NPWT
      was performed on rabbits of the three groups for 7 days. Immediately after
      surgery and on post surgery day (PSD) 7, general observation of wound was
      conducted and tissue around the wound was harvested for determination of dry to
      wet weight ratio. The content of bacteria was counted and the content of tumor
      necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in
      wound was determined by enzyme-linked immunosorbent assay. Fibroblasts in wound
      were counted after Masson staining and number of microvessels was counted after
      CD31 antibody immunohistochemical staining. Data were processed with analysis of
      variance for repeated measurement, LSD-t test, paired samples t test, and
      Bonferroni correction. Results: (1) Immediately after surgery, there was no
      granulation tissue in basal wound of rabbits in the three groups, with rich blood
      supply and obvious edema. On PSD 7, much granulation tissue was found in basal
      wound of rabbits in the three groups, with no or mild edema and no obvious
      redness and swelling in wound edge. (2) There were no significant differences in
      dry to wet weight ratios of tissue around the wound among and within the three
      groups immediately after surgery and on PSD 7 (with F values respectively 0.70
      and 0.09, t values from 0.17 to 0.52, P values above 0.05). (3) Immediately after
      surgery, the content of bacteria in wounds of rabbits in groups PD, BD, and SBD
      was respectively (603.0+/-146.0) *10(4,) (573.0+/-63.0) *10(4,) and (590.0+/
      100.0)*10(4) colony-forming unit (CFU)/g, with no significant difference among
      them (F=0.13, P>0.05). On PSD 7, the content of bacteria in wounds of rabbits in
      groups PD, BD, and SBD were respectively (5.4+/-0.8) *10(4,) (4.6+/-0.9) *10(4,)
      and (3.5+/-0.9)*10(4) CFU/g. Among them, the content of bacteria in wounds of
      rabbits in group SBD was lower than that in groups PD and BD, respectively (with
      t values respectively 3.78 and 2.29, P<0.05 or P<0.01). The content of bacteria
      in wounds of rabbits in the three groups on PSD 7 was decreased compared with
      that immediately after surgery (with t values from 10.05 to 21.81, P values below
      0.01). (4) There was no significant difference in content of TNF-alpha, IL-1beta,
      and IL-6 in wounds of rabbits in the three groups immediately after surgery and
      on PSD 7 (with F values from 0.10 to 1.89, P values above 0.05). The content of
      TNF-alpha in wounds of rabbits in the three groups on PSD 7 was significantly
      higher than that immediately after surgery (with t values from 2.93 to 5.01,
      P<0.05 or P<0.01). (5) There was no significant difference in amount of
      fibroblasts in wounds of rabbits in the three groups immediately after surgery
      and on PSD 7 (with F values respectively 0.01 and 0.81, P values above 0.05). The
      amount of fibroblasts in wounds of rabbits in the three groups on PSD 7 was
      larger than that immediately after surgery (with t values from 4.78 to 11.58, P
      values below 0.01). (6) There was no significant difference in number of
      microvessels in wounds of rabbits in the three groups immediately after surgery
      and on PSD 7 (with F values respectively 2.42 and 2.49, P values above 0.05). The
      number of microvessels in wounds of rabbits in the three groups on PSD 7 was
      larger than that immediately after surgery (with t values from 7.17 to 11.14, P
      values below 0.01). Conclusions: SBD is better at inhibiting the growth of
      bacteria. PD, BD, and SBD have almost the same effects on reducing tissue edema
      and inflammatory reaction, and on promoting the accumulation of collagen fibers
      and tissue vascularization.

PMID- 28763912
TI  - [A new chapter in noncommunicable diseases prevention and control in China: a
      comment on"National Medium and Long-term Plan on Prevention and Control of
      Noncommunicable Diseases (2017-2025)"].

PMID- 28763913
TI  - [Analysis of psychological status and relevant factors of patients with
      esophageal and gastric cardia precancerous lesions in Linzhou of Henan].
AB  - Objective: To explore the psychological status and related factors in patients
      with precancerous of esophageal and gastric cardia in Linzhou of Henan. Methods:
      Clinical psycho-rating scale of Social Support Rating Scale (SSRS), Self-Rating
      Anxiety Scale (SAS, score >=50 points with symptoms of anxiety) and Self-Rating
      Depression Scale (SDS, score >=53 points with the symptoms of depression) were
      applied to survey life events and psychological status of subjects who aged 40-69
      years old and participated in"The Early diagnosis and Early Treatment"program in
      Linzhou cancer hospital from July 2015 to Jan 2016. Patients with lower
      intraepithelial neoplasia or high-grade intraepithelial neoplasia were selected
      as precancerous lesions (n=118), and patients with normal grade were selected as
      healthy controls (n=210). Compare the differences of the scores between the two
      groups, and the logistic regression model was used to analyze the related factors
      of precancerous lesions and psychological status of the study subjects. Results:
      Precancerous lesions included esophageal (72 cases), gastric cardia (40 cases),
      esophageal and cardia dual source (6 cases); Precancerous lesions and healthy
      controls aged (57.17+/-7.71) and (53.12+/-7.99) years old, the difference was
      statistically significant (P<0.001). The anxiety and depression scale showed that
      the scores of SAS and SDS scores in the precancerous lesions were (37.18+/
      10.01), (40.44+/-8.37) points, and (34.02+/-6.63), (38.49+/-8.73) points in
      control group, the difference was statistically significant (P=0.002, 0.032).
      While the social support total score (38.26+/-5.26), and subjective support score
      (24.08+/-3.83) and objective support score (7.50+/-1.89) in control group were
      all higher than those of precancerous group (36.80+/-6.18, 23.01+/-3.93, 6.93+/
      1.57), and the difference were statistically significant (P=0.024, 0.016, 0.004).
      In addition, the Logistic analysis showed that subjects with low objective social
      support, subjective social support and anxiety symptoms were more likely to
      develop precancerous lesions, and the OR were 0.81, 0.72 and 1.05, respectively
      (P=0.028, 0.005, 0.009). Conclusion: Social support, anxiety and depression
      status may be related to the occurrence and development of esophageal and gastric
      cardia precancerous lesions.

PMID- 28763914
TI  - [A case-control study: association between oral hygiene and oral cancer in non
      smoking and non-drinking women].
AB  - Objective: To evaluate the influence of oral hygiene on risk of oral cancer in
      non-smoking and non-drinking women. Methods: From September 2010 to February
      2016, 242 non-smoking and non-drinking female patients with pathologically
      confirmed oral cancer were recruited in a hospital of Fuzhou, and another 856 non
      smoking and non-drinking healthy women from health examination center in the same
      hospital were selected as control group. Five oral hygiene related variables
      including the frequency of teeth brushing, number of teeth lost, poor prosthesis,
      regular dental visits and recurrent dental ulceration were used to develop oral
      hygiene index model. Unconditional logistic regression was used to calculate odds
      ratios (OR) and 95% confidence intervals (95%CI). The area under the receiver
      operating characteristic curve (AUROC) was used to evaluate the predictability of
      the oral hygiene index model. Multivariate logistic regression model was used to
      analyze the association between oral hygiene index and the incidence of oral
      cancer. Results: Teeth brushing <2 twice daily, teeth lost >=5, poor prosthesis,
      no regular dental visits, recurrent dental ulceration were risk factors for the
      incidence of oral cancer in non-smoking and non-drinking women, the corresponding
      OR (95%CI) were 1.50 (1.08-2.09), 1.81 (1.15-2.85), 1.51 (1.03-2.23), 1.73 (1.15
      2.59), 7.30 (4.00-13.30), respectively. The AUROC of the oral hygiene index model
      was 0.705 9, indicating a high predictability. Multivariate logistic regression
      showed that the oral hygiene index was associated with risk of oral cancer. The
      higher the score, the higher risk was observed. The corresponding OR (95%CI) of
      oral hygiene index scores (score 1, score 2, score 3, score 4-5) were 2.51 (0.84
      7.53), 4.68 (1.59-13.71), 6.47 (2.18-19.25), 15.29 (5.08-45.99), respectively.
      Conclusion: Oral hygiene could influence the incidence of oral cancer in non
      smoking and non-drinking women, and oral hygiene index has a certain significance
      in assessing the combined effects of oral hygiene.

PMID- 28763915
TI  - [Pickled food, fish, seafood intakes and oral squamous cell carcinoma: a case
      control study].
AB  - Objective: To investigate the effects between fish, seafood and pickled food
      intakes on oral squamous cell carcinoma (OSCC). Methods: A case-control study was
      carried out in Fujian area during September 2010 to December 2016, in which 604
      newly diagnosed primary OSCC cases confirmed by pathological diagnosis were
      collected from hospital and 1 343 control subjects were enrolled from community
      and healthy hospital population. Demographic data, history of smoking drinking
      and tea drinking, oral hygiene status and dietary behaviors (fish, seafood and
      pickled food intakes) were collected by in-person interviews using a standard
      questionnaire.Using unconditional logistic regression to estimate adjusted odds
      ratios (ORs) and corresponding 95% confidence intervals (CIs) to assess the
      effects of fish, seafood and pickled food intakes on OSCC. Analysis stratified by
      smoking, alcohol drinking and bad prosthesis to explore the possible difference
      in association between subgroups. Multiplicative interactions and additive
      interactions between fish and bad prosthesis, seafood and alcohol drinking,
      pickled food and bad prosthesis were assessed by unconditional logistic
      regression, relative excess risk due to interaction (RERI), attributable
      proportion due to interaction (AP) and synergy index (S). Results: The average
      age of case group and control group were separately (58.69+/-13.92) years old and
      (59.27+/-11.37) years old (chi(2)=4.75, P=0.191). The people whose fish and
      seafood intakes >=3 times/week had the lower risk of OSCC, the adjusted OR
      (95%CI) values were 0.63 (0.52-0.77) and 0.51 (0.41-0.64); The stratified
      analysis indicated that the people having bad prosthesis had the lower risk of
      OSCC if they eating fish >=3 times/week, and the adjusted OR (95%CI) values was
      0.53 (0.39-0.71); the people having bad prosthesis had the higher risk of OSCC if
      they eating pickled food >=3 times/week, the adjusted OR (95%CI) values was 1.37
      (1.02-1.88). Regularly eating seafood can decrease the risk of OSCC for non
      smokers, smokers, non-drinkers, drinkers, people without bad prosthesis and had
      bad prosthesis, the adjusted OR (95%CI) values were 0.49 (0.36-0.68), 0.52 (0.37
      0.73), 0.41 (0.31-0.55), 0.77 (0.51-0.96), 0.49 (0.36-0.67), 0.59 (0.42-0.83).
      Crossover analysis showed fish and bad prosthesis exist multiplication
      interaction relationship (adjusted OR=0.66, 95%CI: 0.44-0.97) and additional
      interaction relationship (RERI=-0.81, 95%CI:-1.43--0.19; AP=-0.76, 95%CI:-1.35-
      0.17; S=0.08, 95%CI: 0.01-0.98); pickled food and bad prosthesis exist
      multiplication interaction relationship (adjusted OR=1.63, 95%CI: 1.06-2.51) and
      addition interaction relationship (RERI=0.65, 95%CI:0.08-1.22; AP=0.36,
      95%CI:0.10-0.62; S=5.19, 95%CI:1.32-54.49). Conclusion: Reducing the consumption
      of pickled food, quitting smoking and limiting alcohol consumption, and regularly
      eating fish and seafood can prevent the occurrence of OSCC.

PMID- 28763916
TI  - [The coping styles and its relationship with quality of life among 1 968 female
      breast cancer patients in Shanghai in 2014].
AB  - Objective: To study the coping styles and its relationship with quality of life
      among part of the female breast cancer patients in Shanghai in 2014. Methods: In
      August of 2014, 1-3 block groups affiliated to Shanghai Cancer Rehabilitation
      Club were selected from each of the 17 districts of Shanghai by convenient
      sampling method. Respondents were recruited from these block groups via putting
      up posters in the community or top three hospitals nearby. The inclusion criteria
      were as follows: female, aged from 18 to 80 years old; the initial diagnosis or
      primary tumor was breast cancer, and active treatments including surgery,
      radiotherapy and chemotherapy were finished; capable of basic reading and
      comprehension, and there was no communication disorder; daily activities were not
      limited, and with no mental disorder or dysgnosia. Totally 2 205 respondents were
      included. Questionnaire survey was conducted to collect the information of
      demographic characteristics, disease characteristics, result of European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      (EORTC QLQ-C30), and result of the Ways of Coping Inventory-Cancer Version (WOC
      CA). 1 968 valid questionnaires were withdrawn. The results of respondent
      characteristics and WOC-CA were under descriptive analysis, and the differences
      of coping styles among groups of different demographic characteristics were
      compared using t test. In addition, we analyzed the correlation between
      respondents' coping styles and quality of life using partial correlation
      analysis. Results: The average age of the 1 968 respondents was (58.7+/-7.4)
      years old, and BMI was (24.4+/-5.4) kg/m(2). The score of positive coping styles
      was 2.04+/-0.41, and the score of negative coping styles was 1.79+/-0.33. The
      scores of Physical Functioning (PF), Role Functioning (RF), Cognitive Functioning
      (CF), Emotional Functioning (EF), Social Functioning (SF), and Global Health (GH)
      were 83.40+/-12.18, 90.80+/-15.92, 80.72+/-16.29, 84.67+/-15.19, 80.99+/-20.91,
      65.27+/-21.21, respectively. Positive coping styles correlated with PF, EF, and
      GH positively, and the correlation coefficients were separately 0.581 (P=0.046),
      0.593 (P=0.045), 0.770 (P<0.001). Negative coping styles correlated with RF, CF,
      EF, and SF negatively, and the correlation coefficients were separately-0.672
      (P=0.021),-0.815 (P=0.005),-0.121 (P<0.001),-0.123 (P<0.001). Conclusion: Part of
      the female breast cancer patients in Shanghai in 2014 mainly adopted positive
      coping styles, and in general the positive coping styles correlated with quality
      of life positively and negative coping styles correlated with quality of life
      negatively.

PMID- 28763917
TI  - [Analysis of the patterns of female breast cancer incidence in Shanghai, 2003
      2012].
AB  - Objective: To analyze the patterns of female breast cancer and their incidence in
      Shanghai during 2003-2012, and to compare them with international data. Methods:
      The data of female breast cancer cases diagnosed between 2003 and 2012 were
      collected from the Shanghai Cancer Registry. The record of cancer cases included
      the patient's name, gender, date of birth, permanent and residential address,
      diagnosis site or name, histological type, date of first diagnosis, diagnostic
      basis and diagnostic stage, etc. Data source of cancer incidence of World,
      Developed Countries, Developing Countries, East Asia and China in 2012 sourced
      from GLOBOCAN 2012 database of the WHO International Agency for Research on
      Cancer (IARC); and the data of USA during 2008-2012 was collected from SEER 18
      database from Surveillance, Epidemiology, and End Results Program of the National
      Cancer Institute (NCI). Incidence indicators of Shanghai female breast cancer
      were calculated, including the average cases, median age, average age,
      proportion, crude rate, age-specific rate and age-standardized rate. Results:
      During 2003-2012, 41 991 new cases of female breast cancer were diagnosed in
      Shanghai, with an average of 4 199 cases per year, accounting for 17.23% among
      total new female cancer cases, ranking first in female cancer incidence in
      Shanghai during 2003-2012, with a crude incidence rate of 60.90 per 100 000 and
      an age-standardized incidence rate of 33.90 per 100 000. During 2008-2012, an
      average 4 528 new cases of female breast cancer was diagnosed per year in
      Shanghai, with 16.97% among total female cancer cases. The median age was 56
      years old and the mean age was 57.73 years old. The crude rate was 64.23 per 100
      000 and the age-standardized rate was 35.00 per 100 0000, which was higher than
      those of China (22.1 per 100 000), Eastern Areas (27.0 per 100 000) and
      Developing Counties (31.3 per 100 000), and lower than that of World (43.1 per
      100 000), and Yellow Race Population of USA (68.77 per 100 000). During 2003
      2007, on average, 3 869 new cases of female breast cancer were diagnosed per year
      in Shanghai, accounting for 17.54% of total female cancer cases. The median age
      was 53 years old and the mean age was 56.44 years old. The crude rate was 57.42
      per 100 000 and the age-standardized rate was 32.69 per 100 000. There was a
      continuing peak stage spanned 25 years old from 50 to 74 years old, during 2008
      2012. Compared with those of 2003-2007, the beginning age group of the continuing
      peak stage was delayed for 5 years old and the ending age group was delayed for
      10 years old. Conclusion: The age-standardized incidence rate in Shanghai was
      higher than those of China, Eastern Areas and Developing Counties, and lower than
      that of World, and that of Yellow Race Population of USA; Compared with 2003
      2007, the crude rate and age-standardized rate increased, the median age, mean
      age and the beginning and ending age group of the continuing peak stage were
      delayed.

PMID- 28763919
TI  - [Report of cancer incidence and mortality in Jiangsu Province in 2013].
AB  - Objective: To estimate the cancer incidence and mortality in Jiangsu, 2013.
      Methods: Up to June 2016, registration data in 2013 from 35 cancer registries in
      Jiangsu was collected by Jiangsu Provincial Central Cancer Registry. All data
      were checked and evaluated by the method and criteria of data quality control
      making by the National Central Cancer Registry, data from 34 registries' data
      were eligible and accepted as pooled data. Stratified by urban and rural, gender,
      age and cancer site, crude incidence/mortality rate, age-specific
      incidence/mortality rate, age-standardized incidence/mortality rate by Chinese
      standard population, age-standardized incidence/mortality rate by world standard
      population, composition, cumulative incidence/mortality rate (0-74 age years old)
      and the 10 leading cancers were calculated. Cancer incidence and mortality were
      estimated by using provincial population of Jiangsu in 2013. Chinese population
      census in 2000 and World Segi's population were used to age-standardize incidence
      and mortality. Results: All 34 cancer registries (10 in urban and 24 in rural
      areas) covered a total of 38 938 470 population (19 682 921 in males and 19 255
      549 in females), accounted for 51.12% of whole provincial population in 2013. It
      was estimated that new cancer cases and cancer deaths were 232.6 thousands (136.7
      thousands in males and 95.9 thousands in females) and 155.3 thousands (99.7
      thousands in males and 55.6 thousands in females), respectively. The crude
      incidence rate in Jiangsu in 2013 was 305.22/100 000, age-standardized incidence
      rate by Chinese standard population and by world standard population were
      184.04/100 000 and 181.16/100 000, respectively, with cumulative incidence rate
      (0-74 age years old) of 21.38%. The crude mortality rate was 203.94/100 000, age
      standardized mortality rate by Chinese standard population and by world standard
      population were 116.28/100 000 and 115.12/100 000, respectively, with cumulative
      mortality rate (0-74 age years old) of 13.11%. Cancers of lung, esophagus,
      stomach, liver, colorectum and female breast were the most common cancers in
      Jiangsu, accounting for about 71% of all new cancer cases in 2013. Lung cancer,
      esophageal cancer, stomach cancer, liver cancer and colorectal cancer were the
      leading cause of cancer death, accounting for about 74% of all cancer deaths.
      Conclusion: The crude incidence and mortality rate of cancer in Jiangsu Province
      were at a high level. For the most common cancers such as lung, esophagus,
      stomach, liver, colorectum and female breast cancer, effective prevention and
      control activities should be strengthened.

PMID- 28763918
TI  - [The association between single-nucleotide polymorphisms in IL6, IL10 genes and
      the susceptibility to primary hepatic carcinoma in Shunde District of Foshan
      City].
AB  - Objective: To investigate the association between single nucleotide polymorphisms
      (SNP) in cytokine IL6, IL10 genes and the susceptibility to primary hepatic
      carcinoma(PHC) of Shunde district in Guangdong Province. Methods: Patients from
      two hospitals in Shunde District of Foshan City were selected from October 2010
      to October 2012. Case group inclusion criteria includedprimary liver cancer;
      local residents of Shunde or living in Shunde for more than 10 years. The control
      group inclusion criteria included: patients visited ENT, general surgery and
      physical examination department in the same hospital during the same period;
      Local residents or living in Shunde for 10 years and above. The control group was
      matched 1?1 by gender, and age (+/-3 years old) with case group. A total of 306
      subjects were collected. Questionnaires were used to investigate the information
      including demographic characteristics, PHC status survey and so on. The venous
      blood was collected from each subject to extract DNA, and to detect label SNP
      site and genotype. Hardy-Weinberg equilibrium was detected in the control group
      by the goodness-of-fit chi(2) test. Multivariate conditional logistic regression
      was used to estimate the relationship between IL6 (rs1800796), IL10 (rs1800871,
      rs1800872)genes polymorphisms and susceptibility to PHC. Results: There were 264
      males and 42 females both in the case group and the control group, with an
      average age of (55.84+/-11.49) and (55.83+/-11.67) years old respectively
      (t=0.011, P=0.992). The frequencies of IL6 (rs1800796), IL10 (rs1800871) and IL10
      (rs1800872) genotypes in the control group were in accordance with the Hardy
      Weinberg equilibrium, which indicated the population was representative (all P
      values>0.05). Conditional logistic regression analysis showed that compared with
      the AA genotype and AA+AC genotype of IL10(rs1800872), CC genotype increased the
      risk of PHC by 2.02 times (OR=3.02, 95%CI:1.21-7.56)and 1.89 times (OR=2.89,
      95%CI:1.19-7.04)respectively after the smoking history, eating fish history,
      drinking history, chronic hepatitis B infection, and family history of liver
      cancer adjusted. No statistical association was found between SNP in cytokine IL6
      (rs1800796) and the susceptibility to PHC (P>0.05). Conclusion: The results
      indicated that people who carried CC genotype in rs1800872 of IL10 gene have an
      increasing risk of PHC.

PMID- 28763920
TI  - [An analysis of factors associated with timeliness of antiretroviral therapy
      initiation among newly diagnosed HIV/AIDS from 2010 to 2014 in China].
AB  - Objective: To analyze timeline of antiretroviral therapy (ART) initiation among
      newly diagnosed HIV/AIDS from 2010 to 2014, as well as influencing factors.
      Methods: Data from the Chinese HIV/AIDS Comprehensive Response Information
      Management System was used to collect newly diagnosed HIV/AIDS cases from January
      1, 2010 to December 31, 2014. Inclusion criteria of HIV/AIDS were confirmed cases
      and clinically diagnosed HIV positive, Chinese mainland cases, 14 years old and
      above, the first CD4(+)T lymphocyte <=350 cells/MUl in the follow up period. A
      total of 177 971 HIV/AIDS cases were included in this study. The general
      demographic characteristics (gender, age, ethnicity, education, occupation,
      etc.), infection routes, sample sources, CD4(+)T lymphocyte level and other
      information were collected from the database. Chi square test was used to analyze
      univariate factor of the timeliness of ART initiation. Multivariate logistic
      regressions were used to analyze potential factors associated with timeliness of
      ART initiation. Results: Out of the 17 7971 cases, 130 679 (73.4%) were males.
      The proportion of the timeliness of ART initiation was 55% (97 915). The
      proportion of timeline of ART within 15 d increased from 26.4% (4 319/16 388) in
      2010 to 39.7% (20 212/50 889) in 2014. The highest proportion was in the group of
      patients infected by illegal blood (plasma) donation, which was 38% (945). The
      proportion of timeline of ART within 30 d increased from 43.2% (7 077/16 388) in
      2010 to 63% (32 070/50 889) in 2014.The highest proportion was in the group of
      patients infected by heterosexual transmission, which was 58.3% (73 098).
      Multivariate logistic regression analysis on timeliness of ART showed that the
      factors of timeliness of ART initiation of HIV/AIDS as follow. The possibility of
      timeliness of ART among patients who were female, education of junior high school
      and above, ethnic group of Han, farmers, married were higher, with OR values at
      1.08, 1.09, 1.13, 1.05 and 1.12. The possibilities of timeliness of ART in group
      of patients aging 25-34, 35-44, 45-54 and >=55 years old were higher than that of
      the group of patients aging 15-24 years old, with OR values at 1.13, 1.31, 1.46
      and 1.51, respectively. The possibilities of timeliness of ART among the
      homosexuals, injection drug use and sexual contact plus injection drug use cases
      were lower than that of the heterosexuals, with OR values at 0.86, 0.59 and 0.72,
      respectively. The possibilities of timeliness of ART among patients whose HIV
      diagnosis from hospitals and detention centers were lower than that of patients
      whose HIV diagnosis from volunteer testing and counseling, with OR values at
      separately 0.90 and 0.29. The possibilities of timeliness of ART among patients
      whose CD4(+)T lymphocyte at 50-99, 100-199, 200-350 cells/MUl were lower than
      that of the patients whose CD4(+)T lymphocyte count at 0-49 cells/MUl, with OR
      values at 0.84, 0.64 and 0.40, respectively. All the P values above was<0.05.
      Conclusion: The proportion of timeliness of ART increased annually from 2010 to
      2014. Those who were men, unmarried or divorced, at younger age, injection drug
      use, diagnosis from hospitals and detention centers and high CD4(+)T lymphocyte
      levels were related to the timeliness of ART.

PMID- 28763921
TI  - [A survey on high-risk behaviors and HIV infection among men having sex with men
      who use drugs in Tianjin in 2016].
AB  - Objective: To analyze the characteristics of high risk sexual behaviors and HIV
      infectious status among men who have sex with men (MSM) who use drugs in Tianjin
      in 2016. Methods: From April to December in 2016, MSM who use drugs in Tianjin
      were targetedly and extensively mobilized to receive testing by snowball sampling
      method. The inclusion criteria were as follows: men aged 18 years old and above;
      have had oral or anal sex with men in the last 6 months; have had drug abuse
      history in the last 6 months, including the use of rush poppers, 5-Methoxy
      diisopropyltryptamine (5-MeO-DiPT), and Methamphetamine Synthesis substances; and
      with no mental disorder or mental deficiency. In this study, 302 MSMs were
      recruited to collect information of social demographic characteristics, drug
      abuse situation, sexual behavior after drug use, HIV test and the infectious
      status was collected through the online questionnaire, and the descriptive
      analysis was conducted. Results: From January to December 2016, a total of 302
      subjects were recruited, among whom 194 (64.2%) aged 21-30 years old, 223 (73.8%)
      were unmarried and 28 (9.3%) were students. In the past 6 months, 297 (98.3%)
      used rush poppers, 31 (10.3%) used 5-MeO-DiPT, and 14(4.6%) used Methamphetamine
      Synthesis substances. The proportion of having sex after using the three types of
      drugs were 87.9% (n=261), 83.9% (n=26) and 92.9% (n=13), 85.5% (n=254), 87.1%
      (n=27) and 92.9% (n=13) of the subjects reported the sexual pleasure and sexual
      desire increased after using drugs, respectively. After using the three types of
      the drugs,58.6% (n=174), 83.9% (n=26) and 92.9% (n=13) of the subjects reported
      the duration of each sexual activity prolonged. In the past 3 months,48.3%
      (n=146) had stable sexual partners, 72.5% (n=219) had temporary sexual partners
      and 12.3% (n=37) had group sexual behaviors. 41 out of 302 subjects were HIV
      positive with the HIV positive rate at 13.6%. Conclusion: Most of the MSM who use
      drugs were young, and always had sex when they use drugs. There is a relatively
      high HIV prevalence in this population.

PMID- 28763922
TI  - [Analysis on death from adverse event following immunization surveillance system
      of Shandong Province during 2011-2016].
AB  - Objective: To analyze the occurrence and death of Adverse Event Following
      Immunization (AEFI) in Shandong province. Methods: Collecting the information of
      AEFI cases from 2011 to 2016, which were reported through the National AEFI
      Management System in Shandong province up to January 15, 2017. The autopsy
      reports of death following immunization were issued by the qualified
      institutions. The inoculation data from 2011 to 2016 was obtained through
      Immunization Information Management System of Shandong province. Chi-square test
      was used to compare the incidence rate of AEFI and mortality related to
      immunization among different time and age groups. Results: A total of 189 864 512
      doses of vaccine were administered in Shandong province during 2011-2016, the
      total number of AEFI cases was 89 973 and the incidence rate of AEFI was 473.88/1
      000 000. The number of death cases was 52 and the mortality rate was 0.27/1 000
      000. The incidence rate of AEFI from 2011 to 2016 respectively was 273.63/1 000
      000, 405.22/1 000 000, 479.88/1 000 000, 545.13/1 000 000, 500.66/1 000 000, and
      627.09/1 000 000 (P<0.001), respectively. The mortality rate from 2011 to 2016
      was 0.17/1 000 000, 0.16/1 000 000, 0.25/1 000 000, 0.39/1 000 000, 0.26/1 000
      000, and 0.40/1 000 000 (P=0.285), respectively.The mortality rates of HepB, BCG
      and IPV were the top three. There was statistical significance of the mortality
      rate among different month-old children (P<0.001). The highest mortality rate
      was<2 month-old (1.09/1 000 000), and the next was 4-5 month-old (0.54/1 000
      000), and the lowest was >=10 month-old (0.06/1 000 000). The mortality rate of
      spring (from February to April), summer (from May to July), autumn (from August
      to October) and winter (from November to January of next year) was 0.41/1 000
      000, 0.16/1 000 000, 0.08/1 000 000 and 0.48/1 000 000 (P<0.001), respectively.
      Among 52 death cases, 26 cases were anatomized, including 3 rare vaccine reaction
      following immunization and 23 coincidental events; 26 cases were not anatomized,
      including 17 coincidental events and 9 unknown causes. Conclusion: The AEFI
      mortality rate of<2 month-old, spring and winter, and the second dose was higher
      than else, which was similar to normal child mortality. Immunization did not
      increase the risk of death, and the most deaths following immunization were
      coincidental events.

PMID- 28763923
TI  - [Effect of menopausal status on onset of impaired fasting glucose and type 2
      diabetes mellitus].
AB  - Objective: To investigate the relationship between menopausal status at different
      FPG levels and the risk of new onset of impaired fasting glucose (IFG) and type 2
      diabetes mellitus (T2DM). Methods: Female subjects were selected from the females
      who joined in the epidemiological survey between May and September in 2009 in six
      counties of Guanlin Village and Xushe Village in Yixing City in Jiangsu Province
      by cluster sampling method. Subjects with diabetes at baseline or pre-menopause
      with age above 65 years old or surgical menopause were excluded. Finally there
      were 2 084 eligible subjects included in this study. According to FPG at
      baseline, subjects were categorized into two groups as normal FPG group (FPG<5.6
      mmol/L) and IFG group (5.6<=FPG<=6.9 mmol/L). Follow-up study was conducted from
      May in 2014 to January in 2016. Cox regression model was used to investigate the
      association between menopausal factors and IFG and T2DM among groups based on
      FPG. Results: The average age of subjects at baseline was 58.08 (51.74-65.82)
      years old, and the number of post-menopausal women was 1 631 (78.3%). The number
      of subjects in normal FPG group was 1 569 (75.3%), and in IFG group was 515
      (24.7%). There were 104 subjects with new onset T2DM among which 34 subjects from
      normal FPG group and 70 subjects from IFG group. And there were 199 subjects with
      new onset IFG in normal FPG group. Among subjects with normal FPG, the incidence
      density of IFG in post-menopausal women (2 752/100 000 person-years) was
      statistically higher than that in premenopausal women (1 670/100 000 person
      years) (P<0.001). After age and BMI adjusted, post-menopausal women had a higher
      risk of having IFG in normal FPG subjects with hazard ratio (HR) at 2.60
      (P<0.001). Among subjects with normal FPG, the risk of new onset IFG decreased in
      post-menopausal women with menopause age increasing after age and BMI adjusted,
      with HR at 0.96 (P=0.046). No statistical association was found between
      menopausal factors and risk of T2DM either in the overall subjects or in the
      subgroups(P>0.05). Conclusion: Menopause can increase the risk of IFG incidence
      in subjects with normal FPG. The incidence of IFG decreases with the menopause
      age increasing.

PMID- 28763924
TI  - [Association between the time of sedentary behaviors and risk of type 2
      diabetes].
AB  - Objective: To explore the relationship between the time of sedentary behaviors
      and the risk of type 2 diabetes mellitus (T2DM) among rural adults in Henan
      Province. Methods: A total of 1 227 adults from Houzhai village in Zhengzhou City
      and Qiaomiao village in Jiaozuo City in Henan Province were randomly selected to
      participate in the survey; each of them finished a questionnaire and accepted
      physical examination and test of biochemical indicators. The participants were
      divided into case and control groups according to whether suffering from T2DM. A
      Pearson linear correlation and linear regression model analysis were used to
      investigate the relevance between the time of sedentary behaviors and fasting
      plasma glucose (FPG); meanwhile, a multi factor logistic regression model was
      used to analyze the relationship between the time of sedentary behaviors and
      T2DM. Results: The average FPG level among the participants was (5.4+/-2.5)
      mmol/L, and the average time of sedentary behaviors was (234.5+/-156.5) min per
      day. The prevalence rate of T2DM in subgroups whose time of sedentary behaviors
      were separately 0-<2.5, 2.5-<4.5, 4.5-<6.5 and >=6.5 h/day were 15.8% (72/457),
      19.3% (73/379), 16.7% (35/210) and 20.4% (37/181), respectively. There was a
      linear regression relationship between the time of sedentary behaviors(x) and
      FPG(y), the regression equation was: y=5.081+0.001x (t=3.01, P=0.003). Logistic
      regression model analysis showed that participants whose time of sedentary
      behaviors >=6.5 h/day had significantly higher risk of T2DM than those whose time
      of sedentary behaviors between 0-2.4 h/day (OR=1.77, 95%CI: 1.11-2.81) after age
      and gender adjusted. However, the associations only exist in males and adults
      >=50 years old according to sex and age stratification. It showed that
      participants with sedentary time >=6.5 h/day had significantly higher risk of
      T2DM than those with sedentary time between 0-<2.5 h/d, with the corresponding OR
      (95%CI) at 2.34 (1.21-4.52) and 2.22 (1.19-4.16), respectively. Conclusion: The
      prolonged sedentary time is a risk factor of type 2 diabetes. After
      stratification by gender and age, the correlation only found in males and adults
      aged >=50 years old.

PMID- 28763925
TI  - [The situation of social support and its relationship with antenatal depression
      among 1 075 Zhejiang primiparas in their third trimesters].
AB  - Objective: To investigate the situation of social support (SS), and explore its
      relationship with antenatal depression (AD) among Zhejiang primiparas in their
      third trimesters. Methods: From March to August 2016, a cross-sectional study was
      conducted and the questionnaire was used at the outpatient consulting room of one
      maternity hospital in Hangzhou. Inclusion criteria includes the primiparas over
      18 years old, gestation from 30 to 36 weeks, been able to understand and complete
      the questionnaires independently, no family history and history of mental
      disorders and no use of psychotropic drugs, without serious illness and so on.
      Exclusion criteria was that the primiparas were unable to complete all the
      contents of the questionnaire and of poor compliance. 1 150 questionnaires were
      actually given out, and 1 075 questionnaires were valid, so the valid rate was
      93.48%. AD was evaluated by the Edinburgh Postnatal Depression Scale (EPDS) and
      SS was evaluated by the Perceived Social Support Scale (PSSS). SS between the non
      AD group and the AD group was compared. The correlation between SS and AD was
      analyzed. Binary logistic regression model was used to assess the relationship
      between SS and AD. The level of SS was divided by average scores, groups lower
      than the average score was defined as the low-score group, groups higher than the
      average score was defined as the high-score group. Results: The prevalence of AD
      (score>=9) was 27.3% (293/1 075) among Zhejiang primiparas in their third
      trimesters. The scores of family support, friend support and other support, and
      the total score of SS among the non-AD group were 24.80+/-2.83, 23.40+/-3.00,
      21.91+/-3.54 and 70.11+/-7.92, respectively, which were higher than those in the
      AD group (22.71+/-3.88, 21.45+/-3.59, 19.95+/-3.97, 64.10+/-10.01), (t values
      were 8.43, 8.29, 7.83 and 9.25, respectively, P<0.001 for all). The scores of
      family support, friend support and other support, and the total score of SS were
      negatively correlated with AD (rs values were-0.26,-0.25,-0.22 and-0.28,
      respectively, P<0.001 for all). Compared with low-score group, the scores of
      family support, friend support and other support, and the total score of SS among
      the high-score group had a lower risk of antenata depression among primiparas in
      their third trimesters, OR(95%CI) values were 0.56 (0.41-0.77), 0.66(0.47-0.92),
      0.57(0.41-0.79) and 0.36(0.27-0.48), respectively. Conclusion: The prevalence of
      AD among Zhejiang primiparas was relatively high, and AD was negatively
      associated with SS level. We suggest adding SS in community pregnancy health
      management service in the future.

PMID- 28763926
TI  - [Analysis of association between appendicular skeletal muscle mass index and main
      anthropometric parameters among overweight and obese adults in China].
AB  - Objective: To investigate the associations between the appendicular skeletal
      muscle mass index and main anthropometric parameters, and to provide clues for
      preventing the reduction of skeletal muscle mass among overweight and obese
      adults in China. Methods: 1 488 volunteered participants who resided in Beijing
      longer than one year, between 22 and 55 years old, with self-report BMI >=24
      kg/m(2) were recruited from April to May 2014. 171 participants whose BMI <=24
      kg/m(2) or with organic diseases at the first physical examination were excluded,
      finally 1 317 overweight/obese participants (male and female were 507, and 810,
      respectively) were enrolled into the present study. After measuring the
      anthropometric parameters and body composition by the DXA, Pearson correlation
      analysis and multiple linear regression models were used to analyze the
      associations between the appendicular skeletal muscle mass index and main
      anthropometric parameters. Results: The average age of males and females was
      (35.6+/-8.4) and (38.2+/-9.4) years old, respectively. The females' mean levels
      of body fat percentage, BMI, waist circumference, hip circumference, and bone
      mineral density were (41.59+/-4.14)%, (29.00+/-3.75) kg/m(2), (92.56+/-9.00) cm,
      (101.74+/-6.75) cm, and (1.20+/-0.10) g/cm(2), respectively; and the males' mean
      levels were (34.22+/-4.61)%, (30.07+/-4.12) kg/m(2), (99.63+/-9.49) cm, (102.93+/
      7.28) cm, and (1.28+/-0.11) g/cm(2), respectively. The mean level of appendicular
      skeletal muscle mass and skeletal muscle mass index in males were (26.98+/-3.88),
      and (8.96+/-1.02) kg, respectively, which were significantly higher than it in
      females ((18.57+/-2.61), and (7.26+/-0.83) kg, respectively) (P<0.001). For male,
      the correlation coefficients of skeletal muscle mass index with BMI, waist
      circumference, hip circumference, body fat percentage and bone mineral density
      were 0.814, 0.601, 0.637, 0.558, and 0.434, respectively; for female, the
      correlation coefficients of skeletal muscle mass index with BMI, waist
      circumference, hip circumference, body fat rate and bone mineral density were
      0.761, 0.534, 0.585, 0.610, and 0.304, respectively. The correlations were
      statistically significant (P<0.001). Multiple linear regression analysis showed
      that the skeletal muscle mass index of male decreased with the increase of age
      (beta=-0.01, 95%CI:-0.01-0.00) and body fat percentage (beta=-0.13, 95%CI:-0.15-
      0.12) (P<0.05), while increased with the increase of BMI (beta=0.31, 95%CI: 0.29
      0.32) and bone mineral density (beta=0.54, 95%CI: 0.10-1.01) (P<0.05). The
      skeletal muscle mass index of female decreased with the increase of age (beta=
      0.01, 95%CI:-0.01-0.00) and body fat percentage (beta=-0.12, 95%CI:-0.14--0.12)
      (P<0.05), while increased with the increase of BMI (beta=0.26, 95%CI: 0.25-0.28)
      and hip circumference (beta=0.01, 95%CI: 0.00-0.02) (P<0.05). Conclusion: The
      skeletal muscle mass index of male was higher than it of female. For male, the
      skeletal muscle mass index might be associated with age, BMI, body fat percentage
      and bone mineral density. While for female, the skeletal muscle mass index might
      be associated with age, BMI, body fat percentage and hip circumference.

PMID- 28763927
TI  - [Factors associated with malnutrition among infants and young children aged 6-23
      months in poor rural areas in Hunan Province, China].
AB  - Objective: To describe the situation and identify factors associated with
      malnutrition among infants and young children aged 6-23 months in poor rural
      areas in Hunan Province in 2015. Methods: 8 735 rural infants and young children
      aged 6-23 months in 30 poor counties of Wuling Mountains and Luoxiao Mountains in
      Hu'nan province were selected by township-level probability proportional to size
      sampling (PPS) in August 2015, infants' body length and weight were measured, and
      questionnaires were used to collect infants' information on personal and family,
      and feeding status in the past 24 h. The prevalence of stunting, underweight and
      wasting were calculated according to the Growth Standards of Child Aged Under 7
      in China which was established in 2009 by Community Health Department of National
      Health and Family Planning Commission, China (formerly Chinese MOH), and the
      prevalence of malnutrition was calculated according to the classification of
      children with anthropometric failure. Multi non-conditional logistic regression
      model were used to analyze factors associated with malnutrition among infants and
      young children aged 6-23 months. Results: The prevalence of malnutrition among
      infants and young children aged 6-23 months was 13.7% (1 198/8 735), the
      prevalence of stunting, underweight and wasting among infants and young children
      aged 6-23 months were 4.8% (419/8 735), 9.7% (849/8 735) and 6.1% (531/8 735)
      respectively. Compared with male group, the OR value of malnutrition for the
      female group was 1.16; Compared with Han ethnic group, the OR value of
      malnutrition for the Miao and Tujia ethnic group were 0.83 and 0.66,
      respectively; Compared with mother with an education level of primary school or
      below, the OR value of malnutrition for the mother with junior high school,
      senior high school and university or above education were 0.65, 0.61 and 0.56,
      respectively; Compared with father with an education level of primary school or
      below, the OR value of malnutrition for the father with senior high school and
      university or above education were 0.71 and 0.61 respectively; Compared with
      normal birth weight group, the OR value of malnutrition for the low birth weight
      group and high birth weight group were 2.85 and 0.27 respectively; Compared with
      normal delivery group, the OR value of malnutrition for the premature delivery
      group was 1.37; all P values<0.05. Conclusion: The prevalence of malnutrition
      among infants and young children aged 6-23 months in poor rural areas in Hunan
      province in 2015 was high; Infants and young children who were female, Han
      ethnic, parents with low education, low birth weight and premature delivery had
      higher risk of malnutrition.

PMID- 28763928
TI  - [Economic burden of stomach cancer in China during 1996-2015: a systematic
      review].
AB  - Objective: To clarify the research status of economic burden of stomach cancer in
      China from 1996 to 2015. Methods: Based on three electronic literature databases
      (China Knowledge Resource Integrated Database, Wanfang Database and PubMed), a
      total of 2 873, 1 244 and 84 articles published during 1996 to 2015 were found,
      respectively, using keywords of"cancer","neoplasms","malignant
      tumor","tumor","economic burden","health expenditure","cost","cost of illness",
      and"China". According to the inclusion and exclusion criteria, 30 literatures
      were included in the final analysis. Then the basic information and study
      subjects, indicators and main results of economic burden were abstracted and
      analyzed. All the expenditure data were discounted to the values in 2013 by using
      China's percapita consumer price index. Results: Totally, 30 articles were
      included, covering 14 provinces and of which 16 were published during 2011-2015.
      One article was based on population-level and the remaining studies were all
      based on individual-level. The number of individual-level articles that reported
      direct medical, non-medical and indirectly economic burden was 29, 1 and 2,
      respectively. The main indicators of direct medical expenditure were expenditure
      per patient (22), per clinical visit (9) and per diem (11), respectively. The
      median expenditure per patient was 7 387-28 743 RMB (CNY), with average annual
      growth rate (AAGR) of 1.7% (1996-2013). The median expenditure per clinical visit
      was 18 504-41 871 RMB (2003-2013), with AAGR of 5.5%. The median expenditure per
      diem was 313-1 445 RMB (1996-2012), with AAGR of 3.7%. Difference was found among
      provinces. Conclusions: The evidence for economic burden of stomach cancer was
      still limited over the past two decades and mainly focused on individual and
      regional levels. An increase and differences in provinces were observed in direct
      medical expenditure. Evaluation on direct non-medical and indirect medical
      expenditure needs to be addressed.

PMID- 28763929
TI  - [A case-control study on consumption of fired food and esophageal cancer].

PMID- 28763930
TI  - [Study of dietary patterns and their influence factors among singleton pregnant
      women in Shaanxi Province of China].

PMID- 28763931
TI  - [Bayesian statistics application in the food safety assessment of dietary
      exposure].

PMID- 28763932
TI  - [The progress and prospect of application of genetic testing technology-based
      gene detection technology in the diagnosis and treatment of hereditary cancer].
AB  - Hereditary cancer is caused by specific pathogenic gene mutations. Early
      detection and early intervention are the most effective ways to prevent and
      control hereditary cancer. High-throughput sequencing based genetic testing
      technology (NGS) breaks through the restrictions of pedigree analysis, provide a
      convenient and efficient method to detect and diagnose hereditary cancer. Here,
      we introduce the mechanism of hereditary cancer, summarize, discuss and prospect
      the application of NGS and other genetic tests in the diagnosis of hereditary
      retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary
      colorectal cancer and other complex and rare hereditary tumors.

PMID- 28763933
TI  - Short-term association between ambient air pollution and pneumonia in children: A
      systematic review and meta-analysis of time-series and case-crossover studies.
AB  - Ambient air pollution has been associated with respiratory diseases in children.
      However, its effects on pediatric pneumonia have not been meta-analyzed. We
      conducted a systematic review and meta-analysis of the short-term association
      between ambient air pollution and hospitalization of children due to pneumonia.
      We searched the Web of Science and PubMed for indexed publications up to January
      2017. Pollutant-specific excess risk percentage (ER%) and confidence intervals
      (CI) were estimated using random effect models for particulate matter (PM) with
      diameter <= 10 (PM10) and <=2.5 MUm (PM2.5), sulfur dioxide (SO2), ozone (O3),
      nitrogen dioxide (NO2), and carbon monoxide (CO). Results were further stratified
      by subgroups (children under five, emergency visits versus hospital admissions,
      income level of study location, and exposure period). Seventeen studies were
      included in the meta-analysis. The ER% per 10 MUg/m3 increase of pollutants was
      1.5% (95% CI: 0.6%-2.4%) for PM10 and 1.8% (95% CI: 0.5%-3.1%) for PM2.5. The
      corresponding values per 10 ppb increment of gaseous pollutants were 2.9% (95%
      CI: 0.4%-5.3%) for SO2, 1.7% (95% CI: 0.5%-2.8%) for O3, and 1.4% (95% CI: 0.4%
      2.4%) for NO2. ER% per 1000 ppb increment of CO was 0.9% (95% CI: 0.0%-1.9%).
      Associations were not substantially different between subgroups. This meta
      analysis shows a positive association between daily levels of ambient air
      pollution markers and hospitalization of children due to pneumonia. However, lack
      of studies from low-and middle-income countries limits the quantitative
      generalizability given that susceptibilities to the adverse effects of air
      pollution may be different in those populations. The meta-regression in our
      analysis further demonstrated a strong effect of country income level on
      heterogeneity.

PMID- 28763934
TI  - Community response to construction noise in three central cities of Zhejiang
      province, China.
AB  - As a common source of environmental noise in China and many developing countries
      worldwide, construction work provokes many complaints and deterioration in
      acoustic climate quality. This paper describes research to obtain an improved
      understanding of people's community response to, and evaluation of, construction
      noise in three central cities of Zhejiang province, China. This involved carrying
      out a social survey using standard questionnaires developed by the International
      Commission on Biological Effects of Noise (ICBEN). A dose-response relationship
      model is established using a quadratic polynomial regression analysis based on
      construction noise exposure measurements from 40 construction sites in Hangzhou,
      Ningbo and Wenzhou. The results of the study indicate that the majority of people
      have a negative attitude to construction noise; the noise ranges between 60 dB
      and 80 dB (compared with 50 dB-70 dB traffic noise in Tianjin), with the
      percentage of highly annoyed people affected increasing from 15%-20% to 30%-40%
      over the range. There also different levels of annoyance depending on the time of
      day, and the location and activities of those affected. Other cultural
      differences are also apparent both between Ningbo/Wenzhou and the more urbane
      citizens of Hangzhou, and the Chinese people and their more noise-tolerant EU and
      Vietnam counterparts. The findings of this study provide a new perspective for
      the study of construction noise that can help local governments have an improved
      understanding of how residents react to construction noise for the purpose of
      selecting construction noise-mitigation projects and introducing construction
      noise-control regulations.

PMID- 28763935
TI  - Parental exposure to microcystin-LR induced thyroid endocrine disruption in
      zebrafish offspring, a transgenerational toxicity.
AB  - Microcystin-LR is the most poisonous and commonly encountered hepatotoxin
      produced by cyanobacteria in an aquatic ecosystem, and it may cause thyroid
      dysfunction in fish. The present study aimed to reveal the effects of
      transgenerational toxicity of MCLR on the thyroid endocrine system under sub
      chronic exposure conditions. Adult zebrafish (F0) were exposed to environmentally
      relevant concentrations (1, 5 and 25 MUg/L) of MCLR for 45 days. The produced F1
      embryos were then tested without further MCLR treatment. In the F0 generation,
      exposure to 25 MUg/L MCLR reduced thyroxine (T4) but not 3, 5, 3'
      triiodothyronine (T3) levels in females, while the T4 and T3 levels were
      unchanged in males. After parental exposure to MCLR, we observed a decreased
      hatching and growth retardation correlated with reduced thyroid hormone levels in
      the F1 offspring. The gene transcription and protein expression along the
      hypothalamic-pituitary-thyroid axis were detected to further investigate the
      possible mechanisms of MCLR-induced thyroid disruption. Our results indicated
      MCLR could disturb the thyroid endocrine system under environmentally relevant
      concentrations and the disrupting effects could be remarkably transmitted to its
      F1 offspring. We regard these adverse effects as a parental transgenerational
      toxicity of MCLR.

PMID- 28763936
TI  - Effect modification of the association between temperature variability and daily
      cardiovascular mortality by air pollutants in three Chinese cities.
AB  - There is limited evidence showing the mortality effects of temperature
      variability (TV) on cardiovascular diseases. The joint effects between TV and air
      pollutants are also less well-established. This study aims to assess the effect
      modification of TV-cardiovascular mortality by air pollutants in three Chinese
      cities (Beijing, Nanjing and Chengdu). Data of daily mortality, air pollutants
      and meteorological factors from 2008 to 2011 was collected from each city. TV was
      calculated as the standard deviation of daily maximum and minimum temperatures
      over exposure days. The city-specific effect estimates of TV on cardiovascular
      mortality were calculated using a quasi-Poisson regression model, adjusting for
      potential confounders (e.g., seasonality and temperature). An interaction term of
      TV and a three-level air pollutants stratum indicator was included in the models.
      Effect modifications by air pollutants were assessed by comparing the estimates
      of TV's effect between pollutant stratums and calculating the corresponding 95%
      confidential interval of the differences. Multivariate meta-analysis was
      conducted to obtain the pooled estimates. The data showed that TV was associated
      with increased risk of cardiovascular mortality, especially for longer TV
      exposure days (0-8 days, TV08). This association was still observed after
      adjusting for air pollutants on current day or the previous two days. Stronger
      estimates were observed in females, but no significant difference between males
      and females was detected, indicating the absence of evidence of effect
      modification by gender. Estimates of TV-cardiovascular mortality varied across
      two season periods (warm and cool season) and age groups, but the evidence of
      effect modification by age and seasons was absent. Regarding the effect
      modification of TV-cardiovascular mortality association by air pollutants, a
      significant effect modification was identified for PM10, but not for NO2 and SO2
      in the whole population for all TV exposure days. This finding also persisted in
      subgroups, specifically in females and the elderly.

PMID- 28763937
TI  - Lethal and sub-lethal effects of commonly used anti-sea lice formulations on non
      target crab Metacarcinus edwardsii larvae.
AB  - The pesticides used by the salmon industry to treat sea lice, are applied in situ
      via a bath solution and are subsequently discharged into the surrounding medium.
      The effects of cypermethrin, deltamethrin, azamethiphos and hydrogen peroxide
      were assessed on the performance of Metacarcinus edwardsii larvae, an important
      crab for Chilean fishery. All larvae were dead or dying after 30 min of exposure
      to cypermethrin and after 40 min to deltamethrin at concentrations 100 and 20
      times lower (0.15 and 0.1 MUg L-1, respectively) than the concentrations and
      exposure times recommended by the manufacturers (CRM) to treat sea lice.
      Azamethiphos affected all larvae at a concentration 10 times lower than CRM.
      Hydrogen peroxide had the lowest detrimental effects, but at the CRM, 100% of the
      larvae were affected. Sub-lethal effects, i.e prolonged developmental time, were
      observed at concentrations lower than CRM. Repeated exposure to azamethiphos
      (0.0625-0.5 MUg L-1) and hydrogen peroxide (188-1500 mg L-1) had effects on
      survival. In conclusion, the pesticides used against parasitic copepod tested
      here, negatively affect non-target crustacean larvae. Due to the product's
      characteristics, the lethal effects of the pyrethroids probably are restricted to
      the time and area of application, while the action of azamethiphos may extend to
      a wider area. Current data are insufficient to accurately dimension the effects
      of these compounds in the field. More research is required to evaluate the
      consequences of prolonged developmental times and/or reduction in appendage
      mobility, so as the effects of these compounds on the pelagic and benthic
      communities.

PMID- 28763938
TI  - Discovery of novel per- and polyfluoroalkyl substances (PFASs) at a fire fighting
      training ground and preliminary investigation of their fate and mobility.
AB  - Aqueous film forming foams (AFFFs) have been released at fire training facilities
      for several decades resulting in the contamination of soil and groundwater by per
      and polyfluoroalkyl substances (PFASs). AFFF compositions are proprietary and
      may contain a broad range of PFASs for which the chemical structures and
      degradation products are not known. In this study, high resolution quadrupole
      time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS) in combination with data
      processing using filtering strategies was applied to characterize and elucidate
      the PFASs present in concrete extracts collected at a fire training ground after
      the historical use of various AFFF formulations. Twelve different fluorochemical
      classes, representing more than 60 chemicals, were detected and identified in the
      concrete extracts. Novel PFASs homologues, unmonitored before in environmental
      samples such as chlorinated PFSAs, ketone PFSAs, dichlorinated PFSAs and
      perfluoroalkane sulphonamides (FASAs) were detected in soil samples collected in
      the vicinity of the fire training ground. Their detection in the soil cores (from
      0 to 2 m) give an insight on the potential mobility of these newly identified
      PFASs.

PMID- 28763940
TI  - Arsenic, manganese and aluminum contamination in groundwater resources of Western
      Amazonia (Peru).
AB  - This paper presents a first integrated survey on the occurrence and distribution
      of geogenic contaminants in groundwater resources of Western Amazonia in Peru. An
      increasing number of groundwater wells have been constructed for drinking water
      purposes in the last decades; however, the chemical quality of the groundwater
      resources in the Amazon region is poorly studied. We collected groundwater from
      the regions of Iquitos and Pucallpa to analyze the hydrochemical characteristics,
      including trace elements. The source aquifer of each well was determined by
      interpretation of the available geological information, which identified four
      different aquifer types with distinct hydrochemical properties. The majority of
      the wells in two of the aquifer types tap groundwater enriched in aluminum,
      arsenic, or manganese at levels harmful to human health. Holocene alluvial
      aquifers along the main Amazon tributaries with anoxic, near pH-neutral
      groundwater contained high concentrations of arsenic (up to 700MUg/L) and
      manganese (up to 4mg/L). Around Iquitos, the acidic groundwater (4.2<=pH<=5.5)
      from unconfined aquifers composed of pure sand had dissolved aluminum
      concentrations of up to 3.3mg/L. Groundwater from older or deeper aquifers
      generally was of good chemical quality. The high concentrations of toxic elements
      highlight the urgent need to assess the groundwater quality throughout Western
      Amazonia.

PMID- 28763939
TI  - Demographic and dietary risk factors in relation to urinary metabolites of
      organophosphate flame retardants in toddlers.
AB  - Organophosphate flame retardants (OPFRs), including Tris (1,3-dichloro-isopropyl)
      phosphate (TDCPP), triphenyl phosphate (TPP), and isopropylated triphenyl
      phosphate (ITP), are increasingly used in consumer products because of the recent
      phase out of polybrominated diphenyl ether (PBDE) flame retardants. OPFRs have
      been widely detected in adults and have been linked to reproductive and endocrine
      changes in adult males. Carcinogenicity and damage to immunologic, neurologic and
      developmental systems have been observed in human cell lines. Young children are
      especially vulnerable to OPFR exposure, but little is known about exposure levels
      or exposure risk factors in this population. We examined parent-reported
      demographic and dietary survey data in relation to OPFR urinary metabolite
      concentrations in 15- to 18-month old toddlers (n = 41). OPFR metabolites were
      detected in 100% of subjects. The metabolite of TPP, diphenyl phosphate (DPP) was
      detected most commonly (100%), with TDCPP metabolite, bis(1,3-dichloro-2-propyl)
      phosphate (BDCPP), detected in 85-95% of samples, and ITP metabolite,
      monoisopropylphenyl phenyl phosphate (ip-DPP), detected in 81% of samples (n =
      21). Toddlers of mothers earning <$10,000 annually had geometric mean DPP
      concentrations 66% higher (p = 0.05) than toddlers of mothers earning
      >$10,000/year (7.8 ng/mL, 95% CI 5.03, 12.11 and 4.69 ng/mL, 95% CI 3.65-6.04,
      respectively). While no dietary factors were significantly associated with OPFR
      metabolite concentrations, results suggested meat and fish consumption may be
      associated with higher DPP and BDCPP levels while increased dairy and fresh food
      consumption may be associated with lower DPP, BDCPP, and ip-DPP levels. Research
      with larger sample sizes and more detailed dietary data is required to confirm
      these preliminary findings.

PMID- 28763941
TI  - Assessment of biodegradation potential at a site contaminated by a mixture of
      BTEX, chlorinated pollutants and pharmaceuticals using passive sampling methods -
      Case study.
AB  - The present study describes a pilot remediation test of a co-mingled plume
      containing BTEX, chlorinated pollutants and pharmaceuticals. Remediation was
      attempted using a combination of various approaches, including a pump and treat
      system applying an advanced oxidation process and targeted direct push injections
      of calcium peroxide. The remediation process was monitored intensively and
      extensively throughout the pilot test using various conventional and passive
      sampling methods, including next-generation amplicon sequencing. The results
      showed that the injection of oxygen-saturated treated water with residual
      hydrogen peroxide and elevated temperature enhanced the in situ removal of
      monoaromatics and chlorinated pollutants. In particular, in combination with the
      injection of calcium peroxide, the conditions facilitated the in situ bacterial
      biodegradation of the pollutants. The mean groundwater concentration of benzene
      decreased from 1349MUg.L-1 prior to the test to 3MUg.L-1 within 3months after the
      calcium peroxide injections; additionally, monochlorobenzene decreased from
      1545MUg.L-1 to 36MUg.L-1, and toluene decreased from 143MUg.L-1 to 2MUg.L-1.
      Furthermore, significant degradation of the contaminants bound to the soil matrix
      in less permeable zones was observed. Based on a developed 3D model, 90% of
      toluene and 88% of chlorobenzene bound to the soil were removed during the pilot
      test, and benzene was removed almost completely. On the other hand, the
      psychopharmaceuticals were effectively removed by the employed advanced oxidation
      process only from the treated water, and their concentration in groundwater
      remained stagnant due to inflow from the surroundings and their absence of in
      situ degradation. The employment of passive sampling techniques, including
      passive diffusion bags (PDB) for volatile organic pollutants and their respective
      transformation products, polar organic compound integrative samplers (POCIS) for
      the pharmaceuticals and in situ soil microcosms for microbial community analysis,
      was proven to be suitable for monitoring remediation in saturated zones.

PMID- 28763942
TI  - Solid sampling ETV-ICPOES coupled to a nebulization/pre-evaporation system for
      direct elemental analysis of glutinous rice by external calibration with standard
      solutions.
AB  - Because glutinous rice flour is consumed by millions of individuals around the
      world, its analysis is essential to ensure its safety. Solid sampling
      electrothermal vaporization (ETV) coupled to inductively coupled plasma optical
      emission spectrometry (ICPOES) allows for a quick analysis, precluding the need
      for time-consuming acid digestion that may also lead to analyte loss or
      contamination. However, the amount of sample that can be introduced without
      extinguishing the plasma is limited to about 4mg. The increase in plasma
      robustness resulting from the concurrent introduction of pre-evaporated water
      aerosol allows the introduction of 8mg of solid sample without extinguishing the
      plasma. This modified set-up was compared to conventional ETV for the
      determination of several elements in three different brands of glutinous rice
      flour. Not only are detection limits improved, but dried aqueous standard
      solutions can be used for external calibration, thereby significantly increasing
      the applicability of solid sampling ETV-ICPOES.

PMID- 28763943
TI  - Sugarcane cells as origin of acid beverage floc in cane sugar.
AB  - Brazil stands out as the largest producer of crystal sugar in the world,
      exporting much of its production to the soft drinks industry. However, the
      chemical composition of sugar may contain numerous compounds that promote the
      formation of acid beverage flocs (ABF), reducing product acceptance. This study
      aimed to identify the chemical composition of ABF using different analytical
      techniques. We could observe the ABF are formed by several chemical classes.
      Regarding the histochemical analysis, we observed the presence of cellular
      sugarcane tissues, which are not fully removed in sugarcane processing. Mineral
      compounds, such as silicon, were found in great amounts by the Scanning electron
      microscopy and energy dispersive system (SEM/EDS) analysis. The mass
      spectrometry, high resolution mass by Q-ToF analysis and MALDI-MS allowed
      identification of compounds, such as p-hydroxybenzaldehyde, vanillin,
      triacontanoic acid, hexadecanoic acid, octadecanoic acid and n-octacosanoic acid,
      in the ABF composition. These compounds are widely found in vegetable tissues,
      confirming that the ABF are formed by tiny particles of plant cells of sugar
      cane.

PMID- 28763944
TI  - Determination of steroid hormones in fish tissues by microwave-assisted
      extraction coupled to ultra-high performance liquid chromatography tandem mass
      spectrometry.
AB  - Steroid hormones produce adverse effects on biota as well as bioaccumulation in
      fish and seafood, making it necessary to develop methodologies to evaluate these
      compounds in samples related to the food chain. This work presents an analytical
      method for evaluating 15 steroid hormones in fish tissue. It is based on
      microwave-assisted extraction and solid-phase extraction coupled to ultra-high
      performance liquid chromatography tandem mass spectrometry (MAE-SPE-UHPLC-MS/MS).
      The proposed method shows appropriate detection limits (0.14-49.0ngg-1),
      recoveries in the range of 50% and good repeatability. After optimization, the
      method was applied to different tissues from two small fishes of the Canary
      Islands that constitute an important level of the food web (Boops boops and
      Sphoeroides marmoratus) and were exposed to the outfall of the Las Palmas de Gran
      Canaria wastewater treatment plant. The concentrations of eight detected
      compounds ranged from below the quantification limits to 3.95MUgg-1.

PMID- 28763945
TI  - Oxidative stability of iron fortified goat and cow milk and their peptide
      isolates.
AB  - The oxidation potential of iron fortified goat and cow milks and casein
      phosphopeptides obtained from each species of milk was determined using
      malondialdehyde as an oxidation product marker. There was a reduction in
      oxidation when iron was 'bound' to milk or peptides compared to free ferrous
      sulphate in solution. However, goat milk produced significantly lower amounts of
      malondialdehyde of 0.46+/-0.04MUgMDA/ml after 3days at 30 degrees C compared to
      the blank of 1.25+/-0.16MUgMDA/ml. The goat peptides produced non-significantly
      different levels of malondialdehyde compared to the blank containing no ferrous
      sulphate.

PMID- 28763946
TI  - Synthesis and in vitro evaluation of peracetyl and deacetyl glycosides of
      eugenol, isoeugenol and dihydroeugenol acting against food-contaminating
      bacteria.
AB  - Essential oils, as well as their separate components, have shown promise as
      alternatives to synthetic preservatives. Therefore, it would be interesting to
      optimize the effect of these compounds and to evaluate their applicability as
      additives in food. To this end, six peracetyl and deacetyl glycosides were
      synthesized from eugenol, isoeugenol and dihydroeugenol. All of the glycosides
      were characterized by IR and NMR. The synthesized compounds and their aglycones
      were evaluated to determine their minimal bactericidal concentrations (MBC)
      against the spoilage food bacteria Escherichia coli, Listeria monocytogenes,
      Staphylococcus aureus and Salmonella enteritidis. All deacetyl glycosides were
      about twice as active as aglycones, and the peracetyl glycosides were, in most
      cases, equipotent with aglycones. The deacetyl glycoside of dihydroeugenol proved
      to be the most active compound against the bacteria tested, with a 0.37% MBC v/v
      for E. coli and 0.18% v/v for the other bacteria.

PMID- 28763947
TI  - Changes in sparkling wine aroma during the second fermentation under CO2 pressure
      in sealed bottle.
AB  - High quality sparkling wine made by the traditional method requires a second
      alcoholic fermentation of a base wine in sealed bottles, followed by an aging
      time in contact with yeast lees. The CO2 overpressure released during this second
      fermentation has an important effect on the yeast metabolism and therefore on the
      wine aroma composition. This study focuses on the changes in chemical composition
      and 43 aroma compounds released by yeast during this fermentation carried out
      under two pressure conditions. The data were subjected to statistical analysis
      allowing differentiating between the base wine and the wine samples taken in the
      middle and at the end of fermentation. The differentiation among wines obtained
      to the end of fermentation with or without CO2 pressure is only achieved by a
      principal component analysis of 15 selected minor compounds (mainly ethyl
      dodecanoate, ethyl tetradecanoate, hexyl acetate, ethyl butanoate and ethyl
      isobutanoate).

PMID- 28763948
TI  - Increased torulene accumulation in red yeast Sporidiobolus pararoseus NGR as
      stress response to high salt conditions.
AB  - Carotenoids represent a class of molecules valuable for food, chemical and
      pharmaceutical industries. As a microbial carotenoid, torulene possesses
      potential health-promoting effects in human. However, few studies have been
      conducted to investigate optimal condition for its large-scale commercial
      production to date. Sporidiobolus pararoseus NGR, a pigmented yeast, was shown
      previously to accumulate considerable amounts of torulene, beta-carotene, and
      torularhodin. In this study, the effect of salt stress on the production of
      carotenoids in S. pararoseus NGR was investigated. After 5days of cultivation,
      the total amount of carotenoids was significantly higher in 0.75M (3.952mg/L) and
      1M (2.89mg/L) NaCl treatments than control (1.636mg/L), respectively. Among them,
      the increase in torulene accumulation is the main contributor to the improvement
      in total amount of carotenoids under 0.75 and 1M NaCl treatments. Together, our
      results should advance the development of metabolic engineering for the
      commercial production of torulene.

PMID- 28763949
TI  - Physical and oxidative stability of fish oil-in-water emulsions fortified with
      enzymatic hydrolysates from common carp (Cyprinus carpio) roe.
AB  - Physical and oxidative stability of 5% (by weight) cod liver oil-in-water
      emulsions fortified with common carp (C. carpio) roe protein hydrolysate (CRPH)
      were examined. CRPH was obtained by enzymatic hydrolysis of discarded roe by
      using Alcalase 2.4L for 30, 60, 90, and 120min to yield different degrees of
      hydrolysis (DH). All the hydrolysates showed in vitro antioxidant activity in
      terms of radical scavenging and chelating properties. CRPH-containing emulsions
      had significantly smaller droplets than control (p<0.05). Besides, CRPH rendered
      rheological stability to the emulsions. It also prevented the loss of tocopherol
      and polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA). CRPH retarded primary and secondary oxidation in
      emulsions as evidenced by peroxide values (PVs) and secondary volatile oxidation
      products, respectively. All the mentioned effects were compared among CRPHs with
      varying DH (7.6-10.2%). However, CRPH-containing emulsions had high levels of 2
      methyl-1-butanol, 3-methyl-1-butanol, and 2-butanone after storage.

PMID- 28763950
TI  - Paper spray mass spectrometry and chemometric tools for a fast and reliable
      identification of counterfeit blended Scottish whiskies.
AB  - A direct method based on the application of paper spray mass spectrometry (PS-MS)
      combined with a chemometric supervised method (partial least square discriminant
      analysis, PLS-DA) was developed and applied to the discrimination of authentic
      and counterfeit samples of blended Scottish whiskies. The developed methodology
      employed the negative ion mode MS, included 44 authentic whiskies from diverse
      brands and batches and 44 counterfeit samples of the same brands seized during
      operations of the Brazilian Federal Police, totalizing 88 samples. An exploratory
      principal component analysis (PCA) model showed a reasonable discrimination of
      the counterfeit whiskies in PC2. In spite of the samples heterogeneity, a robust,
      reliable and accurate PLS-DA model was generated and validated, which was able to
      correctly classify the samples with nearly 100% success rate. The use of PS-MS
      also allowed the identification of the main marker compounds associated with each
      type of sample analyzed: authentic or counterfeit.

PMID- 28763952
TI  - In vitro gastric digestion of cooked white and brown rice using a dynamic rat
      stomach model.
AB  - The changes in physical, rheological and enzyme-digestive behaviours of cooked
      white and brown rice, with similar amylose content, were investigated using a
      dynamic in vitro rat stomach (DIVRS) model and a static soaking method. The brown
      rice had a higher resistance on disintegration and lower gastric emptying rate
      with 53% of the brown rice particles retained in the stomach at the end compared
      to 32% for the white rice. Furthermore, the release rate of maltose from the
      starch hydrolysis was higher in the white rice throughout the digestion
      suggesting the lower glycemic potency of the brown rice. These differences could
      be contributed from the rigid bran layer in the brown rice which would inhibit
      the moisture absorption into rice kernels, limit textural degradation, and
      generate higher gastric digesta viscosity leading to lower mixing and mass
      transfer efficiency. This study suggests that the structural difference could
      affect physiochemical properties during gastric digestion.

PMID- 28763953
TI  - Qualitative and quantitative changes in polyphenol composition and bioactivity of
      Ribes magellanicum and R. punctatum after in vitro gastrointestinal digestion.
AB  - The wild Chilean currants Ribes magellanicum and R. punctatum are a good source
      of polyphenolic compounds. The effect of simulated gastrointestinal digestion
      (GID) on phenolic content, composition and antioxidant capacity was determined.
      The inhibitory activity of the non-digested and digested samples towards
      metabolic syndrome-associated enzymes (alpha-amylase, alpha-glucosidase and
      lipase) was evaluated. The total phenolic (TP) and flavonoid contents (TF)
      decreased by about 50% at the end of the in vitro GID. Main anthocyanins and
      hydroxycinnamic acids were strongly affected by this process, with a loss of
      about 80%. A decrease in the antioxidant activity was observed throughout the
      digestion steps, which was correlated with the reduction in the TP and TF
      content. After the in vitro GID of the samples, only the inhibition of alpha
      glucosidase was preserved. Our results show that the simulated GID modified the
      health-promoting properties of the studied currants.

PMID- 28763951
TI  - Sulfites and the wine metabolome.
AB  - In a context of societal concern about food preservation, the reduction of
      sulfite input plays a major role in the wine industry. To improve the
      understanding of the chemistry involved in the SO2 protection, a series of bottle
      aged Chardonnay wines made from the same must, but with different concentrations
      of SO2 added at pressing were analyzed by ultrahigh resolution mass spectrometry
      (FT-ICR-MS) and excitation emission matrix fluorescence (EEMF). Metabolic
      fingerprints from FT-ICR-MS data could discriminate wines according to the added
      concentration to the must but they also revealed chemistry-related differences
      according to the type of stopper, providing a wine metabolomics picture of the
      impact of distinct stopping strategies. Spearman rank correlation was applied to
      link the statistically modeled EEMF components (parallel factor analysis
      (PARAFAC)) and the exact mass information from FT-ICR-MS, and thus revealing the
      extent of sulfur-containing compounds which could show some correlation with
      fluorescence fingerprints.

PMID- 28763954
TI  - Soymilk-Cow's milk ACE-inhibiting enzyme modified cheese.
AB  - In present study, we developed and optimized soymilk-cow's milk enzyme-modified
      cheese with angiotensin-I converting enzyme inhibitory activity. Bioactive
      peptide production was found to be a multivariable-dependent process. Maximum
      bioactivity of hydrolysates was obtained with prolonged curd proteolysis at an
      increased enzyme concentration. This bioactive cheese paste was subsequently
      spray-dried under different drying conditions to determine the powder sorption
      isotherm properties. Higher drying temperatures resulted in cheese powder with
      weak thermal stability and lower browning indices. Experiments aimed at
      optimizing thermal stability and physical properties revealed that optimal
      conditions for producing cheese powder were an inlet air temperature of 150
      degrees C, a feeding rate of 10%, and an air flow rate of 600Lh-1. Moreover, in
      addition to flavour, the bioactive cheese powders produced from a combination of
      soymilk-cow's milk are of potential source and can be used in the dietary
      management of hypertension.

PMID- 28763955
TI  - Label-free quantification of meat proteins for evaluation of species composition
      of processed meat products.
AB  - This study evaluated the application of label-free, relative quantification of
      highly processed meat proteins to authenticate processed meat products.
      Quantitation was based on proteins for which heat-stable and species-specific
      peptide markers had been detected. Using nano-LC-QTOF-MS/MS, 20 new, heat-stable
      peptide markers unique to chicken, duck and goose were identified, with
      significant scores. The method enabled detection of 1%(w/w) of chicken and
      1%(w/w) pork in a mixture of the meat of three species, as well as 0.8%(w/w) beef
      proteins in commercial poultry frankfurters. The proteins' abundance was computed
      using a spectral matching technique, termed the absolute protein expression
      (APEX) proteomics tool. This method includes a correction factor for each
      protein, based on the peptide MS detection probabilities, which are influenced by
      the physicochemical properties of the peptide. Considerable differences in
      abundance of myofibrillar and sarcoplasmic proteins were observed between samples
      and illegal proportions of ingredients were discovered.

PMID- 28763956
TI  - Mechanism of isomers and analogues of resveratrol dimers selectively quenching
      singlet oxygen by UHPLC-ESI-MS2.
AB  - Stilbenoids, in particular, resveratrol and its dimers are abundantly present in
      Vitis vinifera and proved to be quenchers with selective singlet oxygen. However,
      only a few mechanisms are reported for their complex molecular architectures.
      Hence, UHPLC combined with accurate MS is employed to investigate the photo
      radiation mechanism of resveratrol dimers systematically. I: Resorcinol ring
      exists in Scirpusin A 1, Trans-epsilon-viniferin 2 and Trans-sigma-viniferin 3.
      The photochemical products were 14Da or 16Da higher than reagents and underwent
      an endoperoxide intermediate to quinones; II: [2+2] cyclization of intra
      molecular trans-double bond. The products were 18Da greater than substrates
      thereby cycloaddited to oxygen heterocyclic; III : [4+1], [4+2] cyclization of
      oxetane formed products were 28Da and 44Da higher than 3, 2 and 1. IV : 5-phenol
      2,3-dihydrobenzofuran ring exists in 2 been oxidized, causing the products at
      16Da, 32Da higher than 2. This is the first to reveal the generally regular
      mechanism of stilbenoids quenching singlet oxygen.

PMID- 28763957
TI  - Preconcentration and determination of lead ions in fish and mollusk tissues by
      nanocomposite of Fe3O4@graphene oxide@polyimide as a solid phase extraction
      sorbent.
AB  - The separation and pre-concentration of pb2+ ions from mollusk and fish samples
      were performed by nanocomposite of magnetic graphene oxide-polyimide, as an
      efficient solid-phase extraction sorbent. The nanocomposite was characterized by
      field emission scanning electron microscopy, Fourier transform infrared
      spectroscopy and energy-dispersive X-ray spectroscopy. The parameters affecting
      the extraction processes including: amount of adsorbent, adsorption and
      desorption times, type and volume of the eluent solvent and interfering ions of
      the sample were investigated and optimized. The calibration curve was linear in
      the concentration ranges of 0.8-400MUgL-1 (R2=0.998). The limit of detection and
      quantification were obtained as 0.25MUgL-1 and 0.80MUgL-1, respectively. The
      relative standard deviation was 7.3% and the pre-concentration factor was 141. A
      gastropod, Trochus erithreus, and a muscle tissue of fish, Otolithes ruber, were
      analyzed as real samples and good relative spiked recoveries (95-106%) were
      obtained.

PMID- 28763958
TI  - Electroanalysis and laccase-based biosensor on the determination of phenolic
      content and antioxidant power of honey samples.
AB  - Honey is a functional food widely consumed. Thus, the evaluation of honey samples
      to determine its phenolic content and antioxidant capacity (AOC) is relevant to
      determine its quality. Usually AOC is performed by spectrophotometric methods,
      which lacks reproducibility and practicality. In this context, the
      electroanalytical methods offer higher simplicity and accuracy. Hence, the aim of
      this work was to use of electroanalytical tools and laccase based biosensor on
      the evaluation of AOC and total phenol content (TPC) of honey samples from
      different countries. The antioxidant power established by electrochemical index
      presented good correlation with the spectrophotometric FRAP (Ferric Reducing
      Ability of Plasma) and DPPH (2,2-Diphenyl-1-Picrylhydrazyl) radical scavenging
      assays. Also, TPC results obtained by the biosensor agreed with the Folin
      Ciocalteu (FC) assay. In addition to the semi quantitative results, the
      electroanalysis offered qualitative parameters, which were useful to indicate the
      nature of major phenolic compounds.

PMID- 28763959
TI  - Physico-functional and antioxidant properties of sand-roasted chickpea (Cicer
      arietinum).
AB  - The effect of roasting on the physical, color, thermal, functional and
      antioxidant properties of chickpea was investigated. Chickpea grains were roasted
      in sand at three temperatures (180, 200 and 220 degrees C) for different times
      (5, 10 and 15min). Highest surface area and lowest bulk density were obtained for
      grains roasted at 220 degrees C for 15min. The lightness 'L' of flour decreased
      from 88.48 (unroasted) to 78.73 (220 degrees C, 15min) while significant increase
      in 'a' and 'b' color values was observed from -0.73 to 2.25 and 22.43 to 24.83,
      respectively on roasting. Significant decrease in enthalpy of gelatinization (
      0.14 to -0.46J/g), enthalpy of amylase-lipid complex (4329-2293J/g), total
      flavonoid content (22.89-16.64mg quercetin equivalents/100g) and antioxidant
      activity (22.85-7.36%) was observed upon roasting. However, roasting led to an
      increase in water absorption capacity (0.89-3.64g/g), water absorption index
      (1.97-3.52) and oil absorption capacity (1.60-3.54g/g).

PMID- 28763960
TI  - Water activity in liquid food systems: A molecular scale interpretation.
AB  - Water activity has historically been and continues to be recognised as a key
      concept in the area of food science. Despite its ubiquitous utilisation, it still
      appears as though there is confusion concerning its molecular basis, even within
      simple, single component solutions. Here, by close examination of the well-known
      Norrish equation and subsequent application of a rigorous statistical theory, we
      are able to shed light on such an origin. Our findings highlight the importance
      of solute-solute interactions thus questioning traditional, empirically based
      "free water" and "water structure" hypotheses. Conversely, they support the
      theory of "solute hydration and clustering" which advocates the interplay of
      solute-solute and solute-water interactions but crucially, they do so in a manner
      which is free of any estimations and approximations.

PMID- 28763961
TI  - Impact of extraction techniques on antioxidant capacities and phytochemical
      composition of polyphenol-rich extracts.
AB  - In this work, impact of extraction methods (maceration, decoction, MAE, and UAE)
      on TPC, antioxidant activity, and the mass fraction of phenolics in several plant
      extracts (Punica granatum, Juglans regia, Moringa oleifera, and Cassia fistula)
      was investigated. The results showed that, despite the nature of matrix, the
      highest values of TPC in all samples were obtained by MAE as follows: PP (18.92+/
      0.11), ML (15.19+/-0.11), HL (12.69+/-0.16), and WS (12.80+/-0.11) mg GAEg-1
      respectively, and exhibited potent antioxidant activity (from 0.28+/-0.01 to
      5.34+/-0.02mgGAEg-1), representing sources of powerful antioxidants. The LC-MS2
      analysis revealed a wide range of phenolics, highlighting their content in
      phenolic acids, flavonoids and lignans. The presence of different phenol
      molecules demonstrated that the extraction method had influence on phytochemical
      profile. Finally, due to its high extraction efficiency, MAE was the more
      effective extraction technique.

PMID- 28763962
TI  - Extraction of bioactive compounds from sesame (Sesamum indicum L.) defatted seeds
      using water and ethanol under sub-critical conditions.
AB  - Sesame seeds contain a vast array of lignans and phenolic compounds having
      important biological properties. An optimized method to obtain these seed
      components was designed by using water and ethanol at high pressure and
      temperature conditions. The maximum concentrations of lignans, total phenolics,
      flavonoids and flavonols compounds were achieved at 220 degrees C extraction
      temperature and 8MPa pressure, using 63.5% ethanol as co-solvent. Under these
      conditions, the obtained sesame extracts gave the best radical scavenging
      capacity. Kinetic studies showed a high extraction rate of phenolic compounds
      until the first 50min of extraction, and it was in parallel with the highest
      scavenging capacity. The comparison of our results with those obtained under
      conventional extraction conditions (normal pressure, ambient temperature)
      suggests that recovery of sesame bioactive compounds may be markedly enhanced
      using water/ethanol mixtures at sub-critical conditions.

PMID- 28763963
TI  - Thermoanalytical study of sweetener myo-inositol: alpha and beta polymorphs.
AB  - This work investigates the thermal behavior of alpha and beta myo-inositol
      polymorphs. The inositol is a natural compound widely used in the food industry
      due to its presence in carbohydrate metabolism and its sweet taste. The
      occurrence of polymorphism could change some physico-chemical properties, such as
      melting and sublimation temperatures, and solubility. Therefore, the thermal
      study of polymorphism is important to ensure better conditions for synthesis,
      storage, and transportation of food that contains the myo-inositol. Simultaneous
      Termogravimetry-Differential Thermal Analysis, Photovisual Differential Scanning
      Calorimetry, Polarized Light Thermomicroscopy, and Powder X-ray Diffraction were
      used in investigation. The data show a new thermal event associated to beta myo
      inositol melting at 221.43 degrees C, suggesting that the solid-solid transition
      at 185.68 degrees C was incomplete. The kinetics data made it possible to
      determine the transition lifetime of myo-inositol to occur 5% of solid-solid
      transition at 20 degrees C and 37 degrees C: 126 and 8years, respectively.

PMID- 28763964
TI  - Relationships between surface energy analysis and functional characteristics of
      dairy powders.
AB  - Surface energetics of demineralised whey (DMW), skimmed milk (SMP), phosphocasein
      (PCN) and infant milk formula (IMF) powders were determined by inverse gas
      chromatography (IGC). All four milk powders were amphoteric in nature with the
      dispersive (apolar) component of surface energy dominating the specific (polar)
      contribution. PCN and IMF had the highest and lowest extent of surface
      heterogeneity, respectively. PCN also demonstrated the poorest functional
      properties of the powders examined. In contrast, IMF had excellent flow and
      rehydration properties. Thermodynamic work of cohesion was highest in PCN and may
      have contributed to inadequate rehydration behaviour. Glass transition
      temperature of IMF powder, determined by IGC, suggested a surface dominated by
      lactose. Surface heterogeneity provided a better indicator of functional
      behaviour than total surface energy. IGC is a useful complementary technique for
      chemical and structural analysis of milk powders and allows improved insight into
      the contribution of surface and bulk factors to functionality.

PMID- 28763965
TI  - Structural characterization, formation mechanism and stability of curcumin in
      zein-lecithin composite nanoparticles fabricated by antisolvent co-precipitation.
AB  - Curcumin (Cur) exhibits a range of bioactive properties, but its application is
      restrained due to its poor water solubility and sensitivity to environmental
      stresses. In this study, zein-lecithin composite nanoparticles were fabricated by
      antisolvent co-precipitation technique for delivery of Cur. The result showed
      that the encapsulation efficiency of Cur was significantly enhanced from 42.03%
      in zein nanoparticles to 99.83% in zein-lecithin composite nanoparticles. The Cur
      entrapped in the nanoparticles was in an amorphous state confirmed by
      differential scanning calorimetry and X-ray diffraction. Fourier transform
      infrared analysis revealed that hydrogen bonding, electrostatic interaction and
      hydrophobic attraction were the main interactions among zein, lecithin, and Cur.
      Compared with single zein and lecithin nanoparticles, zein-lecithin composite
      nanoparticles significantly improved the stability of Cur against thermal
      treatment, UV irradiation and high ionic strength. Therefore, zein-lecithin
      composite nanoparticles could be a potential delivery system for water-insoluble
      bioactive compounds with enhanced encapsulation efficiency and chemical
      stability.

PMID- 28763966
TI  - Novel acetylcholinesterase inhibitors from Zijuan tea and biosynthetic pathway of
      caffeoylated catechin in tea plant.
AB  - Zijuan tea is a special cultivar of Yunnan broad-leaf tea (Camellia sinensis var.
      assamica) with purple buds, leaves, and stems. Phytochemical study on this tea
      led to the discovery of three hydroxycinnamoylated catechins (HCCs) (1-3), seven
      other catechins (4-10), three proanthocyanidins (11-13), five flavones and
      flavone glycosides (14-18), two alkaloids (19, 20), one steroid (21), and one
      phenylpropanoid glycoside (22). The isolation and structural elucidation of the
      caffeoylated catechin (1) by means of spectroscopic techniques were described. We
      also provide the first evidence that 1 is synthesized via a two-step pathway in
      tea plant. The three HCCs (1-3) were investigated on their bioactivity through
      molecular modeling simulation and biochemical experiments. Our results show that
      they bind acetylcholinesterase (AChE) tightly and have strong AChE inhibitory
      activity with IC50 value at 2.49, 11.41, 62.26MUM, respectively.

PMID- 28763967
TI  - A feasibility quantification study of total volatile basic nitrogen (TVB-N)
      content in duck meat for freshness evaluation.
AB  - Total volatile basic nitrogen (TVB-N) content is one of the core indicators for
      evaluating freshness of duck meat. Visible and near-infrared (Vis/NIR)
      reflectance spectroscopy was implemented in this study to determine the TVB-N
      content in duck breast meat. Quantitative calibration models were built by
      partial least square regression (PLSR) between the spectral data and the measured
      TVB-N values. The different spectral pre-processing methods were employed and
      synergy interval partial least squares and principal component analysis methods
      were used to select important wavelengths. In comparison, the prediction model
      with full spectra after multiplicative scatter correction pre-processing yielded
      optimum results with a root mean squared error for the prediction set (RMSEP) of
      1.060mg/100g and a correlation coefficient (RP) of 0.859. The results of this
      study demonstrated the feasibility of the quantification method for total
      volatile basic nitrogen (TVB-N) content in duck meat based on Vis/NIR
      spectroscopy technique as an objective tool.

PMID- 28763968
TI  - Variation of strontium stable isotope ratios and origins of strontium in Japanese
      vegetables and comparison with Chinese vegetables.
AB  - To evaluate the utility of 87Sr/86Sr ratio for determining the geographical
      provenance of vegetables, we compared 87Sr/86Sr ratios and Sr concentrations in
      five vegetable species grown in Japan and China, and we also examined the
      relationships between 87Sr/86Sr ratios in vegetables, the soil-exchangeable pool,
      irrigation water, and fertilizer from 20 Japanese agricultural areas. The
      vegetable 87Sr/86Sr ratios in Japan were similar for all species within a given
      agricultural area, but tended to be low in northeast Japan and high in southwest
      Japan. The median 87Sr/86Sr ratio in Japanese vegetables was similar to that in
      fertilizer, suggesting that in addition to rock-derived Sr, vegetables contain Sr
      derived from fertilizers. In most cases, the 87Sr/86Sr ratios for the Japanese
      and Chinese vegetables differed by approximately 0.710. Linear discriminant
      analysis using both 87Sr/86Sr and the Sr concentration allowed more accurate
      discrimination between vegetables from the two countries.

PMID- 28763969
TI  - Identification and determination of selenohomolanthionine - The major selenium
      compound in Torula yeast.
AB  - Torula yeast (Candida utilis) was found to metabolize selenium in a totally
      different way to Brewer's yeast (S. cerevisiae) leading to the biosynthesis of
      selenohomolanthionine (SeHLan), a major selenium compound accounting for 60-80%
      of the total selenium. The identity of SeHLan was confirmed by retention time
      matching in hydrophilic ion interaction chromatography (HILIC) with inductively
      coupled plasma mass spectrometric detection (ICP MS) using a custom synthesized
      standard molecule and by HILIC - Orbitrap MS and MS-MS fragmentation.
      Selenohomolanthionine escapes the current assays for the organic character of Se
      rich yeast based on the protein-bound selenomethionine determination. A HILIC -
      ICP MS method was developed for the quantitative determination of
      selenohomolanthionine in yeast supplements with a detection limit of 146ng/g.

PMID- 28763970
TI  - Residual detection of buparvaquone, nystatin, and etomidate in animal-derived
      food products in a single chromatographic run using liquid chromatography-tandem
      mass spectrometry.
AB  - A reliable and highly sensitive screening method based on liquid chromatography
      coupled withtriple-quadrupoleelectrospray tandemmass spectrometry (LC-MS/MS)
      analysis has been developed for the detection and quantification of three
      veterinary drugs, including buparvaquone, nystatin, and etomidate impurity B CRS.
      The tested drugs were extracted from samples of porcine muscle, pasteurized whole
      milk, and eggs using 10mM ammonium formate in acetonitrile followed by liquid
      liquid purification with n-hexane. Chromatographic separation was achieved on a
      Phenomenex Luna C18 analytical column using 0.1% formic acid in ultrapure water
      (A) and acetonitrile (B) as mobile phases. All the matrix-matched calibration
      curves were linear (R2>=0.9756) over the concentration levels of the drugs
      tested. Recovery at two spiking levels (equivalent to the limit of quantification
      (LOQ)=5ng/g and 2*LOQ) ranged from 72.88% to 92.59% with intra- and inter-day
      precisions <17%, except for porcine muscle spiked with 5ng/g nystatin
      (RSD=25.15%). Samples collected from markets located in Seoul, Republic of Korea,
      tested negative for all the drugs analyzed. In summary, this method is suitable
      for screening and quantifying the selected drugs in a single chromatographic run
      and with high selectivity in animal-derived food products meant for human
      consumption.

PMID- 28763971
TI  - Impact of trehalose on the activity of sodium and potassium chloride in aqueous
      solutions: Why trehalose is worth its salt.
AB  - Trehalose is revered for its multiple unique impacts on solution properties,
      including the ability to modulate the salty and bitter tastes of sodium and
      potassium salts. However, the molecular mechanisms underlying trehalose's effect
      on taste perception are unknown. Here we focus on the physico-chemical effect of
      trehalose to alter the activity of monovalent salts in aqueous solution. Using a
      modified isopiestic methodology that relies on contemporary vapor pressure
      osmometry, we elucidate how trehalose modifies the thermodynamic chemical
      activity of sodium and potassium chloride, as well as the effect of the salts on
      the sugar's activity. We find that trehalose has a specific impact on potassium
      chloride that is unlike that of other sugars or polyols. Remarkably, especially
      at low salt concentrations, trehalose considerably elevates the activity (or
      chemical potential) of KCl, raising the salt activity coefficient as high as ~1.5
      its value in the absence of the sugar. Moreover, in contrast to their action on
      other known carbohydrates, both KCl and NaCl act as salting-out agents towards
      trehalose, as seen in the elevated activity coefficient compared with its value
      in pure water (up to ~1.5 higher at low sugar and salt concentrations). We
      discuss the possible relevance of our findings to the mechanism of trehalose
      taste perception modification, and point to necessary future directed sensory
      experiments needed to resolve the possible link between our findings and the
      emerging biochemical or physiological mechanisms involved.

PMID- 28763972
TI  - Next generation nutraceutical from shrimp waste: The convergence of applications
      with extraction methods.
AB  - In recent years considerable progress in health therapy makes a significant
      improvement in natural nutraceuticals. Shrimp is a valuable natural sea food and
      is processed by removing head, tail and carapace as waste. The large amounts of
      waste produced by sea food industries capitulate, recoverable nutraceutical
      compound astaxanthin. This review emphasizes the chemistry and role of
      astaxanthin in pigmentation. The study highlights progress in applications and
      describes the current extraction methods starting with chemical to the best eco
      friendly microbial processes. Relevant literature on the methods giving summary
      of results obtained using each approach has been reviewed and critically
      discussed. Intense research in advancing extraction methods to enhance
      productivity and to meet the demands of the consumer was discussed in future
      challenges. Further, aimed at collating valuable information about applications
      and recent extraction methodologies will promote a concept of intake of "a
      nutraceutical a day may keep the doctor away".

PMID- 28763973
TI  - Cold storage of 'Manzanilla de Sevilla' and 'Manzanilla Cacerena' mill olives
      from super-high density orchards.
AB  - The suitability of the cold storage (2 degrees C) of fruit to maintain the
      quality of 'Manzanilla de Sevilla' and 'Manzanilla Cacerena' intended for virgin
      olive oil extraction was investigated. This temperature was effective in keeping
      the best commercial category of oil quality in both manually harvested olives and
      in mechanically harvested 'Manzanilla Cacerena' fruits for 11days. Mechanical
      harvesting induced significant decreases in oxidative stability and in the main
      phenolic compounds contents in the oils during cold storage and, only initially,
      in the total volatiles, regardless of the cultivar considered. However, the
      contents of volatile esters, associated to fruity flavor, were always higher in
      the oils from mechanically harvested fruits. 'Manzanilla de Sevilla' oils
      exhibited higher total volatiles during fruit cold storage, regardless of the
      harvesting system used.

PMID- 28763974
TI  - Development of low calorie jams with increased content of natural dietary fibre
      made from tomato pomace.
AB  - In this study, four jam formulations were developed, starting with the basic
      formulation (Jam 1) containing sucrose and without added pectin. Sucrose was
      partially (50%) replaced by stevioside in formulations of Jam 2 and 3, while in
      Jam 4 sucrose was completely replaced by fructose and stevioside, making this
      formulation suitable for diabetic patients. Jam formulations 1 and 2, prepared
      without added pectin, were thermally stable in the temperature range of 25-90
      degrees C, which indicate their potential use as fruit fillings. Jam formulations
      3 and 4 were assessed by the sensory panel as more spreadable since tomato pomace
      particles are incorporated in pectin network which acts as a lubricant. Jam
      formulations were characterized by a lower total carbohydrate content (17.23
      43.81%) and lower energy value (87.1-193.7kcal/100g) when compared to commercial
      products. Tomato pomace jams contained 15-20 times more dietary fibre than
      commercial apricot jam.

PMID- 28763975
TI  - Corrigendum to "Identification of bitter compounds in whole wheat bread crumb"
      [Food Chem. 203 (2016) 8-15].

PMID- 28763976
TI  - Corrigendum to "Development and validation of a LC-MS/MS method for the
      determination of isoeugenol in finfish" [Food Chemistry 228 (2017) 70-76].

PMID- 28763977
TI  - Corrigendum to "Thermal degradation kinetics of anthocyanins extracted from
      jucara (Euterpe edulis Martius) and "Italia" grapes (Vitis vinifera L.), and the
      effect of heating on the antioxidant capacity" [Food Chem. 232 (2017) 836-840].

PMID- 28763978
TI  - Biochemical and histological contributions to textural changes in watermelon
      fruit modulated by grafting.
AB  - Increased watermelon fruit flesh firmness is systematically incurred with
      grafting on Cucurbita hybrid rootstocks (heterografting). Possible differences in
      mesocarp cell wall constitution and histology between heterografted, homeografted
      (self-grafted) and non-grafted watermelon were examined, as well as their
      contributions to fruit texture. Firmness correlated positively (r=0.78, p<0.001)
      with cell density (cellsmm-2) which was higher in heterografts (5.83) than
      homeografts (4.64) and non-grafted controls (4.69). Mean cell size was smallest
      in heterografts and correlated negatively (r=-0.75, p<0.001) with firmness. Cell
      wall material, particularly the water-insoluble pectin fractions associated with
      firmness, were highest in heterografts. No associations with firmness were found
      for cell wall neutral sugars and membrane permeability. Higher parenchymatic cell
      density with higher content of alcohol insoluble residue and more abundant water
      insoluble pectin fractions underscore enhanced firmness in heterografts. Possible
      implication of osmolytes in rootstock-mediated cell pressure regulation warrants
      further investigation.

PMID- 28763979
TI  - Preparation of milk protein-vitamin A complexes and their evaluation for vitamin
      A binding ability.
AB  - The recent trends for consumption of low fat and fat free foods have led to an
      increase in deficiencies of vitamin A. Vitamin A is susceptible to light and heat
      and thus require stabilization in aqueous medium. Stability can be improved by
      binding of vitamin A to milk protein. In the present research work, succinylated
      milk proteins were also prepared. 3.2 mol of succinic anhydride/mole of lysine
      content gave maximum degree of succinylation for both sodium caseinate and milk
      protein concentrate. Native, reassembled and succinylated milk proteins were used
      for the preparation of milk protein-Vitamin A (Vit A) complexes. These complexes
      were further evaluated for unbound vitamin A, ability of milk protein to bind
      vitamin A and solubility of protein and vitamin A as affected by complexation.
      Estimation of unbound vitamin A in milk protein-Vit A complexes was carried out
      using ammonium sulphate for precipitation.

PMID- 28763980
TI  - Nutritional composition of mungbean and soybean sprouts compared to their adult
      growth stage.
AB  - This study determined the level of phytonutrients in mungbean and soybean sprouts
      compared to mature mungbean grain and vegetable soybean. The comparison included
      landraces and improved mungbean and soybean varieties to assess the effect of
      breeding on the phytonutrient content of both crops. Sprouting mungbean enhanced
      vitamin C content 2.7-fold compared to mature mungbean grain. Relatively old
      mungbean accessions were superior in protein, calcium (Ca), iron (Fe), zinc (Zn),
      carotenoid and vitamin C content compared to improved mungbean lines at the fully
      mature stage. With regard to nutritional value, the vegetable soybean stage was
      superior to soybean sprouts in terms of content of protein (14% increase), Zn
      (45%), Ca (72%), and Fe (151%). Isoflavones, reported to have beneficial effects
      on human health, are found at high concentrations in soybean sprouts and could
      easily provide the recommended anticarcinogenic dose range from 1.5 to 2.0mg/kg
      of body weight per day.

PMID- 28763981
TI  - Technological properties of milk gels produced by chymosin and wild cardoon
      rennet optimized by response surface methodology.
AB  - The aim of this paper was to optimize extraction conditions of C. cardunculus
      rennet by response surface methodology, in order to maximize its milk-clotting
      activity (MCA). The second objective was to examine the effect of different
      amounts of the optimized extract and the type of milk, on technological
      characteristics of the obtained gels. Results of the central composite design
      showed that the optimum extraction conditions, corresponding to maximum MCA
      (9.550CAU/mL), were selected as follows: Grinding time 30s, pH 3, extraction time
      50min and solid to liquid ratio 15g/100mL. According to technological properties,
      it can be concluded that C. cardunculus extract exhibited an excellent efficiency
      on raw milk, in term of dynamic moduli and gel firmness, as compared to chymosin.
      A good gelation time and WHC were also obtained. Consequently, the optimized C.
      cardunculus rennet has the potential to be employed as an efficient milk-clotting
      agent.

PMID- 28763982
TI  - Microbial cell-free extracts affect the biochemical characteristics and sensorial
      quality of sourdough bread.
AB  - This study aimed to improve the sensorial quality of sourdough wheat bread by the
      addition of cell-free enzyme extracts (CFEs) from Lactobacillus sanfranciscensis
      (SF), Hafnia alvei (HF) and Debaryomyces hansenii (DH). CFEs were suitable
      sources of peptidases, glutamate dehydrogenase and cystathionine gamma-lyase. The
      concentration of free amino acids (FAA) in the sourdoughs containing CFEs was
      higher than the control sourdough, produced without addition of CFEs. The
      community-level catabolic profiles showed that the highest number of
      carbohydrates, polymers and carboxylic acids were consumed in the SF sourdough.
      Breads produced with CFEs were characterized by higher specific volume than the
      control. The use of CFEs impacted on the profile of volatile organic compounds.
      Overall, positive correlations were found between some key-aroma compounds and
      enzyme activities/precursor FAA. The SF bread, characterized by highest level of
      alcohols, received the highest score for aroma and sweetness in the sensory
      analysis.

PMID- 28763983
TI  - Biogenic antioxidative and anti-inflammatory aryl polyketides from the venerid
      bivalve clam Paphia malabarica.
AB  - Chemical investigation of ethyl acetate-methanol extract of the venerid bivalve
      clam Paphia malabarica led to isolation of three unprecedented aryl polyketide
      derivatives, characterized as (E)-12-(17-ethyl-tetrahydro-16-hydroxy-15-(methyl
      pentanoate)-14-oxo-2H-pyran-13-yl)-9-methyl-but-11-enyl benzoate (1), isobutyl-13
      (6-(benzoyloxy)-10-methylpentyl)-tetrahydro-13-methyl-2H-pyran-17-carboxylate (2)
      and (13-(methoxycarbonyl)-11-((E)-18-ethylhexa-16,19-dienyl)-12-propyl-cyclohex
      10-enyl)-methyl-3-hydroxy benzoate (3). The structures of the polyketides were
      assigned by extensive spectroscopic experiments. Compound 1 displayed
      comparatively greater 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical quenching
      potential (50% inhibitory concentration, IC50 ~0.59mg/mL) than commercially
      available alpha-tocopherol (IC50 0.63mg/mL). Potential pro-inflammatory 5
      lipoxygenase (5-LOX) inhibition potential (IC50 0.76-0.92mg/mL) of the
      polyketides in consonant with significantly greater anti-inflammatory selectivity
      indices (anti-cyclooxygense-1IC50/anti-cyclooxygense-2IC50>1) than non-steroidal
      anti-inflammatory agent ibuprofen (0.44) described the safety profile of the
      title compounds. Putative biosynthetic route by means of polyketide synthatase
      biocatalyzed pathways unambiguously established the structural assignments of the
      previously undescribed polyketide analogues. The potential of hitherto
      undescribed polyketides from P. malabarica as natural antioxidative and anti
      inflammatory functional food ingredients was demonstrated in the present study.

PMID- 28763984
TI  - Solvation behavior and sweetness response of carbohydrates, their derivatives and
      sugar alcohols in thiamine HCl (vitamin B1) and pyridoxine HCl (vitamin B6) at
      different temperatures.
AB  - Volumetric properties are important tools to study the solvation behavior of
      solutes and reveal valuable information about solute-solute/cosolute
      interactions. Therefore, standard partial molar volumes at infinite dilution have
      been calculated from density measurements for monosaccharides, their methoxy and
      deoxy derivatives, disaccharides and sugar alcohols in (0.05, 0.15, 0.25 and
      0.35)molkg-1 thiamine HCl(aq) and pyridoxine HCl(aq) solutions over temperature
      range (288.15-318.15)K at pressure, p=0.1MPa. The corresponding transfer volumes,
      expansibilities and apparent massic volumes have been evaluated to examine the
      solvation behavior and the basic taste quality of studied solutes. UV-Vis
      absorption study of these solutes has also been carried out in 1.0*10-4molkg-1
      thiamine HCl and pyridoxine HCl solutions. Results have been compared with our
      previously reported studies carried out in l-ascorbic acid (vitamin C).
      Stereochemical effects on hydration controlled by dominant conformations of
      studied solutes have also been discussed.

PMID- 28763985
TI  - Increase in nitrite content and functionality of ethanolic extracts of Perilla
      frutescens following treatment with atmospheric pressure plasma.
AB  - This study investigated the effect of atmospheric pressure plasma (APP) treatment
      on nitrite content and functionality of plant extracts. Ethanolic extracts of
      Perilla frutescens (EEP) were prepared and treated with APP for 60min. Nitrite
      content increased from 0 to 45.8mg/l in EEP after APP treatment for 60min.
      Antimicrobial activity of EEP against Clostridium perfringens and Salmonella
      Typhimurium was increased by APP with no influence on antioxidative activity
      (p<0.05). Lyophilized EEP (LEEP) treated with APP for 60min contained 3.74mg/g
      nitrite. The control (LEEP without APP) contained no nitrite. The minimum
      inhibitory concentration (MIC) of LEEP for C. perfringens was 200ug/ml. The
      control did not inhibit C. perfringens growth between 25 and 1000ug/ml. MICs of
      LEEP and the control against S. Typhimurium were 25 and 50ug/ml, respectively.
      New nitrite sources with increased antimicrobial activity can be produced from
      natural plants by APP treatment.

PMID- 28763986
TI  - Effective synthesis of magnetic porous molecularly imprinted polymers for
      efficient and selective extraction of cinnamic acid from apple juices.
AB  - An effective strategy was proposed to prepare novel magnetic porous molecularly
      imprinted polymers (MPMIPs) for highly selective extraction of cinnamic acid
      (CMA) from complex matrices. Characterization and various parameters affecting
      adsorption and desorption behaviors were investigated. Results revealed
      adsorption behavior between CMA and MPMIPs followed Freundlich equation
      adsorption isotherm with a maximum adsorption capacity at 4.35mg/g and pseudo
      second-order reaction kinetics with equilibrium time at 60min. Subsequently,
      MPMIPs were successfully used to selectively extract CMA from apple juice with a
      relatively satisfactory recovery (92.7-101.4%). Coupling with high-performance
      liquid chromatography and ultraviolet detection (HPLC-UV), the limit of detection
      (LOD) for CMA was 0.006ug/mL, and the linear range (0.02-10MUg/mL) was wide with
      correlation coefficient at 0.9995. Finally, the contents of CMA in two kinds of
      apple juices were determined as 0.132 and 0.120MUg/mL. Results indicated the
      superiority of MPMIPs in the selective extraction field.

PMID- 28763987
TI  - Changes in ROS production and antioxidant capacity during tuber sprouting in
      potato.
AB  - Potato dormancy is a complex process with an extensive release phase. This study
      investigated involvement of reactive oxygen species during tuber dormancy
      release. We found that tuber sprouting was delayed by treatment with diphenylene
      iodonium chloride, an NADPH oxidase inhibitor; NADPH oxidase catalyze the
      production of ROS. In situ ROS localization and ROS content estimation revealed
      that dormancy release was associated with an accumulation of superoxide anion and
      hydrogen peroxide in tuber buds. The antioxidant compounds and enzymes display
      important changes during the progression of dormancy. The application of Ca2+
      induced superoxide anion production and promoted in vitro tuber bud sprouting.
      Among the seven homologues of NADPH oxidases in potato, the expression of StrbohA
      and StrbohB were detected in particular when dormancy break. In addition, the
      expression of key genes that function in the potato dormancy release are
      discussed in relation to ROS metabolism in other plants.

PMID- 28763988
TI  - Screening bioactivity and bioactive constituents of Nordic unifloral honeys.
AB  - The objective of this study was to screen the antibacterial and antioxidant
      activity of thirty nine honey samples from Finland, Sweden, Norway and Denmark.
      Their physicochemical properties were analysed, antioxidant activity was
      evaluated by DPPH assay and antibacterial activity against Pseudomonas aeruginosa
      and Staphylococcus aureus was assessed by microdilution assay. The honey samples
      obtained were buckwheat, caraway, clover, dandelion, fireweed, heather, lime
      tree, lingonberry, rape, raspberry, sweet clover, willow, mire, honeydew and
      polyfloral. Eleven honey samples showed high antioxidant activity. With 15% honey
      dilution, three unifloral honeys had over 85% inhibition against growth of P.
      aeruginosa and ten honey samples against S. aureus. The buckwheat, raspberry and
      honeydew honeys showed the highest antibacterial and antioxidant activity. An
      unexpectedly high amount of methylglyoxal was found in mire and forest honeys.
      Some phenolic compounds are shown to be plant species-specific floral markers due
      to their appearance in specific unifloral honey samples.

PMID- 28763989
TI  - A modified FOX-1 method for Micro-determination of hydrogen peroxide in honey
      samples.
AB  - Hydrogen peroxide (H2O2) is a major antibacterial activity-associated biomarker
      in honey. Measurement of endogenous H2O2 in honey is of great value in prediction
      of the H2O2-depended antibacterial activity and characterization or selection of
      honey samples for their use as an antibacterial agent or natural food
      preservative. Considering current methods for H2O2 determination are either time
      consuming or complicated with their high-cost, a study was conducted to modify
      and validate the spectrophotometry-based ferrous oxidation-xylenol orange (FOX-1)
      method for micro-determination of H2O2 in honey samples. The result suggested
      that the proposed FOX-1 method is fast, sensitive, precise and repeatable. The
      method was successfully applied for the analysis of a total of 35 honey samples
      from 5 floral origins and 33 geographical origins. The proposed method is low
      cost and easy-to-run, and it can be considered by researchers and industry for
      routine analysis.

PMID- 28763990
TI  - Functional and in vitro gastric digestibility of the whey protein hydrogel loaded
      with nanostructured lipid carriers and gelled via citric acid-mediated
      crosslinking.
AB  - Nanostructured lipid carriers (NLCs) with mean size of 347nm were fabricated and
      added into a heat-denatured whey protein solution. The subsequent crosslinking of
      proteins by citric acid or CaCl2 resulted in the formation of cold-set hydrogels.
      Fourier transform infrared spectroscopy (FTIR) proposed formation of more
      hydrogen bonds in gel due to NLC loading or citric acid-mediated gelation. It was
      also found based on FITR spectroscopy that citric acid crosslinking disordered
      whey proteins. Scanning electron microscopy (SEM) imaging showed a non-porous and
      finely meshed microstructure for the crosslinked gels compared to non-crosslinked
      counterparts. Crosslinking also increased the firmness and water-holding capacity
      of gels. In pepsin-free fluid, a strong correlation existed between reduction in
      gel swellability and digestibility over periods up to 60min due to NLC loading
      and citric acid gelation. However, in peptic fluid, NLC loading and citric acid
      crosslinking brought about much higher decrease in digestibility than
      swellability.

PMID- 28763991
TI  - Combined effects of gamma radiation doses and sodium nitrite content on the lipid
      oxidation and color of mortadella.
AB  - The effects of different doses of gamma radiation (0-20kGy) on the color and
      lipid oxidation of mortadella prepared with increasing nitrite levels (0-300ppm)
      were evaluated using a central composite rotatable design. Higher radiation doses
      increased the redox potential, promoted the lipid oxidation and elevating the hue
      color of the mortadellas. Nevertheless, higher addition of sodium nitrite
      elevated the residual nitrite content, reduced the lipid oxidation and promoted
      the increase of redness and the reduce of hue color of the mortadellas,
      regardless of the radiation dose applied. Nitrite addition had a greater effect
      than irradiation on the quality parameters evaluated, and even at low levels
      (~75ppm), its use decreased the deleterious effects of irradiation at doses as
      high as 20kGy.

PMID- 28763992
TI  - Nutraceutical potential of Byrsonima cydoniifolia fruits based on chemical
      composition, anti-inflammatory, and antihyperalgesic activities.
AB  - In recent years, the fruits of native Brazilian plant species with anti
      inflammatory property have gained prominence due to their properties comparable
      to traditional medicines. This study aimed to chemically characterize and
      evaluate the anti-inflammatory and antihyperalgesic activity of Byrsonima
      cydoniifolia fruit, which is widely used to manufacture ice cream and jellies.
      Our results revealed that the fruit exhibits flavonoid derivatives and stilbenes,
      as trans-piceatannol and resveratrol, as main secondary metabolites. In mice, the
      hydroethanolic extract of fruit reduced the edema, migration of polymorphonuclear
      leukocytes into the peritoneal cavity, as well as abdominal writhings. The
      results demonstrated, for the first time, the presence of stilbenoids in the
      Byrsonima genus and the anti-inflammatory and antihyperalgesic effect of
      Byrsonima cydoniifolia fruits, supporting its potential as a nutraceutical food.

PMID- 28763993
TI  - Phenolic composition and antioxidant properties of koose, a deep-fat fried cowpea
      cake.
AB  - Koose, a West African delicacy, is a side dish prepared by deep frying thick
      cowpea paste. The current research determined the effect of deep-fat frying of
      cowpea paste on its total phenolic content (TPC), phenolic composition and
      antioxidant properties. Four cowpea cultivars comprising two reddish-brown, a
      brownish-cream and cream phenotypes were used. Liquid chromatography-mass
      spectrometry was used to determine phenolic composition of the samples. TPC was
      determined using Folin-Ciocalteu method while radical scavenging capacities were
      by Trolox equivalent antioxidant capacity, oxygen radical absorbance capacity and
      nitric oxide scavenging assays. The phenolic acids identified included benzoic
      and cinnamic acid derivatives. The predominant flavonoid classes were flavan-3
      ols and flavonols. Deep-fat frying of the cowpea pastes decreased their TPC,
      radical scavenging capacities and total quantified flavonoids. The koose
      inhibited radical-induced oxidative cellular and DNA damage. It is concluded that
      koose is a potential functional food that can contribute to alleviating radical
      induced oxidative stress.

PMID- 28763994
TI  - Covering the different steps of the coffee processing: Can headspace VOC
      emissions be exploited to successfully distinguish between Arabica and Robusta?
AB  - This work was performed to evaluate the possible application of PTR-ToF-MS
      technique in distinguishing between Coffea arabica (Arabica) and Coffea canephora
      var. robusta (Robusta) commercial stocks in each step of the processing chain
      (green beans, roasted beans, ground coffee, brews). volatile organic compounds
      (VOC) spectra from coffee samples of 7 Arabica and 6 Robusta commercial stocks
      were recorded and submitted to multivariate statistical analysis. Results clearly
      showed that, in each stage of the coffee processing, the volatile composition of
      coffee is highly influenced by the species. Actually, with the exception of green
      beans, PTR-ToF-MS technique was able to correctly recognize Arabica and Robusta
      samples. Particularly, among 134 tentatively identified VOCs, some masses (16 for
      roasted coffee, 12 for ground coffee and 12 for brewed coffee) were found to
      significantly discriminate the two species. Therefore, headspace VOC analyses was
      showed to represent a valuable tool to distinguish between Arabica and Robusta.

PMID- 28763995
TI  - Extraction, identification and assessment of antioxidative compounds of bran
      extracts of traditional rice cultivars: An analytical approach.
AB  - The antioxidative compounds were extracted by ultrasonic treatment of bran
      extracts of seven pigmented (completely) and non pigmented (sparsely) colored
      rice cultivars followed by assessment of their in vitro antioxidative capacity by
      LC-MS and oxidation/reduction assay based methods. A total of 40-compounds, 7
      phenolic, 9-flavonoids, 9-hydroxycinammic acid derivatives, 3-hydroxybenzoic acid
      derivatives and other glucosides specifically, pro-anthocyanidin trimer and
      procyanidin-B1 (dimer) were indentified in completely colored rice cultivars.
      Higher DPPH radical scavenging activity of pigmented cultivars was due to higher
      percentage of phenolics like thymol, quinicquinic-caffeicacid ester and polar
      dicaffeoylquinic acid; whereas higher lipid peroxidation inhibition was
      attributed to the presence of polar substances such as p-hydroxybenzoicacid,
      procyanidin B1 and quercetin-3-O-rutinoside. The phosphomolybdenum reduction
      capacity was attributed to luteolin-7-O-glucoside, apigenin-7-O-glucoside,
      caffeicacid, myrecitin and phloreticacid. Whereas, grater reducing power of
      pigmented bran was attributed to presence of multiple-OH groups containing
      phenols, flavonoid and hydracinammicacid depicting potential health and
      nutritional effects of these rice cultivars.

PMID- 28763996
TI  - A novel magnetic ion imprinted polymer as a selective magnetic solid phase for
      separation of trace lead(II) ions from agricultural products, and optimization
      using a Box-Behnken design.
AB  - In this work, a magnetic ion-imprinted polymer (Fe3O4@SiO2@IIP) as a novel and
      selective nanosorbent for selective extraction of Pb(II) ions from various
      agricultural products is presented. The novel lead magnetic ion-imprinted polymer
      was synthesized by imidazole as a new ligand and grafted onto the surface of
      Fe3O4@SiO2 NPs. A Box-Behnken (BBD) design was used for optimization of the
      extraction and elution steps. In the selected conditions, the limit of detection
      was 0.48ngmL-1, preconcentration factor was 300, the sorption capacity of this
      new magnetic ion-imprinted polymer was 105mgg-1, and the precision of the method
      (RSD%) for six replicate measurements was found 3.2%. Finally, the feasibility of
      the new magnetic ion-imprinted polymer was evaluated by extraction and
      determination of trace Pb2+ ions in different agricultural products including
      (orange, mango, apple, kiwi, lettuce, broccoli, carrot, squash, eggplant, radish,
      mushroom, cucumber, and tomato).

PMID- 28763997
TI  - Aroma enhancement of cherry juice and wine using exogenous glycosidases from
      mould, yeast and lactic acid bacteria.
AB  - This study investigates the collateral activity of glycosidases in commercial
      pectinase preparations, and the release of aromas from their glycosidic
      counterparts in model cherry juices. It also examines possibilities for further
      enzymatic flavor modifications to cherry wine. The volatile aglycones released
      varied depending on the substrate specificities of the pectinolytic preparation,
      strain of yeast and bacteria used. Considerably larger amounts of monoterpenes,
      aliphatic alcohols and benzene derivatives, were released using pectinolytic
      preparations. The highest concentration of free aglycones was observed following
      hydrolysis with Pektopol PT. This was 93.9% of the total of volatiles detected in
      raw cherry juice. Many aglycones reached or exceeded their odor thresholds,
      enriching the flavor of the juice. The bacteria-derived glicosidases showed 3.4
      times higher activity for free terpenoic and benzenoic aglycones than the yeast
      glycosidases. However, the total aroma in model wines inoculated with bacteria
      was still 88.6% lower than that in natural cherry juice.

PMID- 28763998
TI  - An immunoaffinity column for the selective purification of 3-methyl-quinoxaline-2
      carboxylic acid from swine tissues and its determination by high-performance
      liquid chromatography with ultraviolet detection and a colloidal gold-based
      immunochromatographic assay.
AB  - An immunoaffinity column (IAC) for the selective purification of 3-methyl
      quinoxaline-2-carboxylic acid (MQCA) from porcine muscle and the liver as well as
      the methods for its determination by high-performance liquid chromatography with
      ultraviolet detection (HPLC-UV) and a colloidal gold-based immunochromatographic
      assay (GICA) were developed. This is the first study that describes a clean-up
      method that employs an IAC for the determination of MQCA. Using the HPLC-UV
      method, the limits of detection and limits of quantification for MQCA in
      different samples were 1.0-3.0MUgkg-1 and 4.0-10.0MUgkg-1, respectively. The
      average recoveries of MQCA that was spiked into samples at concentrations of 4.0
      100MUgkg-1 were 80.1-87.7%, with relative standard deviations of less than 8.5%.
      Using the GICA method, the limits of detection for MQCA in different samples were
      10MUgkg-1 and 50MUgkg-1. No false negatives or false positives were observed.

PMID- 28763999
TI  - Antioxidant effects of extra virgin olive oil enriched by myrtle phenolic
      extracts on iron-mediated lipid peroxidation under intestinal conditions model.
AB  - Chelating and free radicals scavenging activities of extra virgin olive oil
      (EVOO) enriched by Myrtus communis phenolic compounds (McPCs), alpha-tocopherol
      and Butylated hydroxytoluene (BHT) were evaluated using chemical assays, 2,2
      diphenyl-1-picrylhydrazyl (DPPH) and Oxygen radical absorbance capacity (ORAC),
      and biological model as 2,2'-azobis (2-aminopropane) dihydrochloride (AAPH) or
      Fe+3/Ascorbic acid (Fe+3/AsA) system mediated peroxidation of l-alpha
      phosphatidylcholine aqueous dispersions stabilized by bile salts (BS) under
      simulated intestinal conditions (pH 7.4). McPC-EEVOO increased significantly the
      neutralization of DPPH radical and AAPH-derived radicals in ORAC assay more than
      alpha-tocopherol and BHT. The phospholipid stability increased by a factor of
      33.6%, 34.8%, 19.3% and 10.7% for myrtle microwave assisted extraction (MAE) and
      conventional extraction (CE) extracts, alpha-tocopherol and BHT, respectively, as
      compared to the control (EVOO without enrichment) in Fe+3/AsA system. But a
      slightly additive effect was observed when AAPH system was used. Our observation
      showed that McPCs may interact positively with EVOO to inhibit phospholipid
      peroxidation, and thus, McPC-EEVOO could be a potential functional food.

PMID- 28764000
TI  - Direct immersion single drop micro-extraction method for multi-class pesticides
      analysis in mango using GC-MS.
AB  - Due the negative effects of pesticides on environment and human health, more
      efficient and environmentally friendly methods are needed. In this sense, a
      simple, fast, free from memory effects and economical direct-immersion single
      drop micro-extraction (SDME) method and GC-MS for multi-class pesticides
      determination in mango samples was developed. Sample pre-treatment using
      ultrasound-assisted solvent extraction and factors affecting the SDME procedure
      (extractant solvent, drop volume, stirring rate, ionic strength, time, pH and
      temperature) were optimized using factorial experimental design. This method
      presented high sensitive (LOD: 0.14-169.20MUgkg-1), acceptable precision (RSD:
      0.7-19.1%), satisfactory recovery (69-119%) and high enrichment factors (20-722).
      Several obtained LOQs are below the MRLs established by the European Commission;
      therefore, the method could be applied for pesticides determination in routing
      analysis and custom laboratories. Moreover, this method has shown to be suitable
      for determination of some of the studied pesticides in lime, melon, papaya,
      banana, tomato, and lettuce.

PMID- 28764001
TI  - Investigation of degradation and penetration behaviors of dimethoate on and in
      spinach leaves using in situ SERS and LC-MS.
AB  - To investigate the degradation and penetration behaviors of the organophosphate
      insecticide dimethoate applied on spinach leaves, in situ SERS and LC-MS methods
      were used to detect dimethoate residue on&in spinach leaves picked on different
      days after treatment (DAT). The SERS and LC-MS methods determined that the
      dimethoate degradation rate followed first-order kinetics, with a half-life of
      3.56 or 4.13days, depending on the respective method. The correlation coefficient
      of quantification value of these two methods was 0.9562. With the SERS method, we
      detected most of the penetrated dimethoate in the depth of 60-110MUm. With the LC
      MS method, we detected dimethoate up to 0.17ng in leaves and that the dimethoate
      on:in ratio of spinach leaves ranged from 562.25 on 0 DAT to 5.23 on 14 DAT. The
      combination of these two methods facilitated a better understanding of the
      behavior and biological fate of pesticides in a complex biological system.

PMID- 28764002
TI  - Purification of phlorotannins from Macrocystis pyrifera using macroporous resins.
AB  - Phlorotannins are secondary metabolites produced by brown seaweed, which are
      known for their nutraceutical and pharmacological properties. The aim of this
      work was to determine the type of macroporous resin and the conditions of
      operation that improve the purification of phlorotannins extracted from brown
      seaweed, Macrocystis pyrifera. For the purification of phlorotannins, six resins
      (HP-20, SP-850, XAD-7, XAD-16N, XAD-4 and XAD-2) were assessed. The kinetic
      adsorption allowed determination of an average adsorption time for the resins of
      9h. The highest level of purification of phlorotannins was obtained with XAD-16N,
      42%, with an adsorption capacity of 183+/-18mgPGE/g resin, and a desorption ratio
      of 38.2+/-7.7%. According to the adsorption isotherm the best temperature of
      operation was 25 degrees C, and the model that best described the adsorption
      properties was the Freundlich model. The purification of phlorotannins might
      expand their use as a bioactive substance in the food, nutraceutical and
      pharmaceutical industries.

PMID- 28764003
TI  - Fundamental study on reactivities of gluten protein types from wheat, rye and
      barley with five sandwich ELISA test kits.
AB  - Monitoring the compliance of gluten-free foods to the regulatory threshold of
      20mg/kg of gluten is essential for celiac disease patients. The different enzyme
      linked immunosorbent assays (ELISAs) for gluten detection each have specific
      characteristics, but there are only a few systematic comparisons. This
      fundamental study compared the specificities and sensitivities of the R5, G12 and
      Skerritt monoclonal and two polyclonal antibodies to well-defined gluten protein
      types (GPT) isolated from wheat, rye and barley flours. Quantitation of protein
      concentrations by reversed-phase high-performance liquid chromatography provided
      independent reference values. The ELISA responses showed high variability
      depending on the type of cereal, the GPT and the antibody used. Overall, omega1,2
      gliadins and gamma-75k-secalins were most reactive, whereas omega5-gliadins and
      gamma-, B- and D-hordeins were detected with the lowest sensitivities. These
      results revealed which GPT each antibody is most sensitive to and provided novel
      insights that will be helpful for appropriate calibration of ELISAs.

PMID- 28764004
TI  - The Gauss-Eyring model: A new thermodynamic model for biochemical and microbial
      inactivation kinetics.
AB  - A new primary model has been developed, using Gaussian distributed populations
      and Eyrings rate constant for the transition state, to describe inactivation
      kinetics of enzymes and micro-organisms subjected to heat and chemical treatment.
      The inactivation of both enzymes and micro-organisms could be associated with the
      irreversible transition to an inactivated state, as suggested by the Lumry-Eyring
      model for protein denaturation and enzyme inactivation. The characteristic
      inactivation model parameters, standard activation enthalpy and entropy, are
      directly related to the reference temperature and Z-value commonly used for
      kinetic analysis in food microbiology. An essential feature of the kinetic model
      is that its parameters, and hence the transition temperature, are treated as
      stochastic variables. The characteristic line shape of the primary model is the
      log-normal distribution. The performance of the model was validated, using
      literature data for enzyme and microbial inactivation over a wide range of
      temperature and pH.

PMID- 28764005
TI  - A novel FT-IR spectroscopic method based on lipid characteristics for qualitative
      and quantitative analysis of animal-derived feedstuff adulterated with ruminant
      ingredients.
AB  - The objective of this study was to explore the ability of Fourier transform
      infrared (FT-IR) spectroscopy to authenticate adulterated animal-derived
      feedstuff. A total of 18 raw meat and bone meals (MBMs), including 9 non-ruminant
      MBMs and 9 ruminant MBMs, were mixed to obtain 81 binary mixtures with specific
      proportions (1-35%). Lipid spectral characteristics were analyzed by FT-IR
      spectroscopy combined with chemometrics. Changes in FT-IR spectra were observed
      as adulterant concentration was varied. The results illustrate ruminant
      adulteration can be successfully distinguished based on lipid characteristics.
      PLS model was established to quantify ruminant adulteration, which was shown to
      be valid (R2P>0.90). Furthermore, the ratios of CC/CO and CC/CH(CH2), as well as
      the number of CH(CH2) in the fatty acids of adulterated lipids, were calculated,
      which showed that differences in the trans fatty acid content and the degree of
      unsaturation were the main contributors to determination of adulteration based on
      FT-IR spectroscopy.

PMID- 28764006
TI  - Potential antioxidant peptides produced from whey hydrolysis with an immobilized
      aspartic protease from Salpichroa origanifolia fruits.
AB  - An aspartic protease from Salpichroa origanifolia fruits was successfully
      immobilized onto an activated support of glutaraldehyde agarose. The immobilized
      enzyme presented higher thermal stability than the free enzyme from 40 degrees C
      to 50 degrees C and high reusability, retaining 54% of the initial activity after
      ten cycles of the process. Whey protein concentrates (WPC) were hydrolyzed with
      both free and immobilized enzyme, reaching a similar degree of hydrolysis of
      approximately 6-8% after 20h. In addition, the immobilized derivate hydrolyzed
      alpha-lactalbumin protein with a higher affinity than beta-lactoglobulin. The
      hydrolysate was ultra-filtrated, and the fractions were evaluated for antioxidant
      activities with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging
      activity method. The fraction containing peptides with a molecular mass below
      3kDa demonstrated a strong radical quenching effect (IC50: 0.48mg/ml). These
      results suggest that hydrolyzed WPC could be considered as a promising source of
      natural food antioxidants for the development of functional food.

PMID- 28764007
TI  - Formation and emission of linalool in tea (Camellia sinensis) leaves infested by
      tea green leafhopper (Empoasca (Matsumurasca) onukii Matsuda).
AB  - Famous oolong tea (Oriental Beauty), which is manufactured by tea leaves
      (Camellia sinensis) infected with tea green leafhoppers, contains characteristic
      volatile monoterpenes derived from linalool. This study aimed to determine the
      formation mechanism of linalool in tea exposed to tea green leafhopper attack.
      The tea green leafhopper responsible for inducing the production of
      characteristic volatiles was identified as Empoasca (Matsumurasca) onukii
      Matsuda. E. (M.) onukii attack significantly induced the emission of linalool
      from tea leaves (p<0.05) as a result of the up-regulation of the linalool
      synthases (CsLIS1 and CsLIS2) (p<0.05). Continuous mechanical damage
      significantly enhanced CsLIS1 and CsLIS2 expression levels and linalool emission
      (p<0.05). Therefore, continuous wounding was a key factor causing the formation
      and emission of linalool from tea leaves exposed to E. (M.) onukii attack. This
      information should prove helpful for the future use of stress responses of plant
      secondary metabolism to improve quality components of agricultural products.

PMID- 28764008
TI  - 2-Methylbutyl acetate in wines: Enantiomeric distribution and sensory impact on
      red wine fruity aroma.
AB  - Enantiomers of 2-methylbutyl acetate were assayed in red and white commercial
      wines from various vintages and origins, using chiral gas chromatography (gamma
      cyclodextrin), revealing the exclusive presence of the S-enantiomeric form.
      Results also confirmed that (S)-2-methylbutyl acetate levels were generally
      higher in red than white wines of the same age, and that acetate levels increased
      gradually during ageing. Olfactory threshold of (S)-2-methylbutyl acetate was
      evaluated at 313ug/L in dilute alcohol solution (12% v/v) and 1083ug/L in a
      fruity aromatic reconstitution, reflecting its presence in wines at subthreshold
      concentrations. At concentrations considerably lower than its olfactory
      threshold, 2-methylbutyl acetate was associated with blackberry-fruit and banana
      notes. It was also revealed that, even at subthreshold concentrations, this
      compound had a modification on the perception of fruity aromas in the matrices
      studied. Sensory profiles highlighted, for the first time, its specific
      contribution to black-, fresh-, and jammy-fruit notes, despite its subthreshold
      concentrations.

PMID- 28764009
TI  - The chitosan affects severely the carbon metabolism in mango (Mangifera indica L.
      cv. Palmer) fruit during storage.
AB  - Mango is a highly perishable fruit with a short post-harvest time due to the
      intense metabolic activity after harvesting. In attempt to evaluate the effects
      of chitosan in mango fruits, it was treated with 0%, 1%, 2% or 3% of chitosan
      solutions, placed into plastic trays, and stored at room temperature. Changes in
      physical and chemical parameters were evaluated. Chitosan delayed the climacteric
      peak, water loss and firmness. Further, few changes in soluble solid content,
      titratable acidity, pH of the pulp as well as in sugar content and decreased
      starch degradation were observed. Altogether, our results suggest chitosan edible
      coating effectively prolongs the quality attributes, affecting basic
      mitochondrial respiration and starch degradation rate.

PMID- 28764010
TI  - Effects of sunlight exclusion on the profiles of monoterpene biosynthesis and
      accumulation in grape exocarp and mesocarp.
AB  - Terpenes are important aroma compounds in table Muscat grape and wine, and their
      content in the berry can be affected by sunlight. The effects of sunlight
      exclusion on monoterpene profiles and relevant gene expression profiles in the
      exocarp and mesocarp of table Muscat grape 'Jingxiangyu' at different development
      stages were thoroughly surveyed by bagging pre-veraison clusters in special
      opaque boxes. The responses of monoterpenes to sunlight treatments varied in
      three types, representatively linalool, ocimene and geraniol. Linalool was the
      most sensitive compound to sunlight, whose biosynthesis was severely inhibited by
      sunlight exclusion and then was elevated by re-exposure. Ocimene and glycosylated
      geraniol showed a certain suppressive and stimulative responses to sunlight
      exclusion respectively. Further transcription analysis revealed that VvPNLinNer1,
      VvCSbOci, VvGT7 and VvGT14 genes were mainly responsible for monoterpene
      accumulation and sensitivity to sunlight. VvDXS2 and VvDXR genes were partially
      related to the differential accumulation of total terpenes under different
      sunlight treatments.

PMID- 28764011
TI  - Galloyl moieties enhance the binding of (-)-epigallocatechin-3-gallate to beta
      lactoglobulin: A spectroscopic analysis.
AB  - The current study was designed to examine the role of galloyl moieties in the
      interaction of beta-lactoglobulin (beta-Lg) with (-)-epigallocatechin-3-gallate
      (EGCG) using fluorescence and CD spectroscopic methods. The interactions with
      beta-Lg were investigated for EGCG, (-)-epigallocatechin (EGC), and the phenolic
      compound methyl gallate (MeG) at pH values 3.0, 5.0 and 7.4. The spectroscopic
      data indicated the binding constants for polyphenol complexes with beta-Lg in
      phosphate buffer pH 7.4 to be in the order of MeG>EGCG>EGC. MeG exhibited the
      strongest quenching efficiency compared to EGCG and EGC, and EGC exhibited the
      weakest quenching efficiency. The quenching efficiency of EGCG on beta-Lg
      fluorescence decreased with increasing pH. Polyphenols binding results in a
      slight secondary structural change of beta-Lg, consistent with the fluorescence
      analysis. This study confirmed that the high binding affinity of EGCG to beta-Lg
      is due to the galloyl functional group.

PMID- 28764012
TI  - Antioxidative mechanisms in chlorogenic acid.
AB  - Although chlorogenic acid (5CQA) is an important ingredient of various foods and
      beverages, mechanisms of its antioxidative action have not been fully clarified.
      Besides electron spin resonance experiment, this study includes thermodynamic and
      mechanistic investigations of the hydrogen atom transfer (HAT), radical adduct
      formation (RAF), sequential proton loss electron transfer (SPLET), and single
      electron transfer - proton transfer (SET-PT) mechanisms of 5CQA in benzene,
      ethanol, and water solutions. The calculations were performed using the M06-2X/6
      311++G(d,p) level of theory and CPCM solvation model. It was found that SET-PT is
      not a plausible antioxidative mechanism of 5CQA. RAF pathways are faster, but HAT
      yields thermodynamically more stable radical products, indicating that in acidic
      and neutral media 5CQA can take either HAT or RAF pathways. In basic environment
      (e.g. at physiological pH) SPLET is the likely antioxidative mechanism of 5CQA
      with extremely high rate.

PMID- 28764013
TI  - Stable isotope labeling-solid phase extraction-mass spectrometry analysis for
      profiling of thiols and aldehydes in beer.
AB  - In this study, we developed a strategy for profiling of thiols and aldehydes in
      beer samples by stable isotope labeling-solid phase extraction-liquid
      chromatography-double precursor ion scan/double neutral loss scan-mass
      spectrometry analysis (SIL-SPE-LC-DPIS/DNLS-MS). A pair of isotope reagents
      (omega-bromoacetonylquinolinium bromide, BQB; omega-bromoacetonylquinolinium-d7
      bromide, BQB-d7) were used to label thiols; while for the aldehydes, a pair of
      isotope reagents (4-(2-(trimethylammonio) ethoxy) benzenaminium halide, 4-APC; 4
      (2-(trimethylammonio) ethoxy) benzenaminium halide-d4, 4-APC-d4) were used. The
      labeled thiols and aldehydes were extracted and purified with solid-phase
      extraction, respectively, followed by LC-MS analysis. Using the proposed SIL-SPE
      LC-DPIS/DNLS-MS methods, 76 thiol and 25 aldehyde candidates were found in beer.
      Furthermore, we established SIL-SPE-LC-MRM-MS methods for the relative
      quantitation of thiols and aldehydes in different beer samples. The results
      showed that the contents of thiols and aldehydes are closely related to the
      brands and origins of beers.

PMID- 28764014
TI  - Generation of bioactive peptides from duck meat during post-mortem aging.
AB  - The objective of this study was to investigate the endogenous release of
      bioactive peptides in duck meat during 7days of post-mortem aging. The
      degradation of muscle proteins led to release of small peptides (<5kDa). The
      peptides formed in the samples after 3days post-mortem exhibited highest DPPH
      radical scavenging, oxygen radical scavenging (ORAC) and ferric reducing
      antioxidant power (FRAP). By using size-exclusion chromatography, the initial
      extract was purified into three fractions (A-C) in which fraction C exhibited the
      highest antioxidant activity. In total 18 peptides were sequenced and identified
      in the fractions by nano LC-MS/MS. Among these peptides, the peptides of fraction
      C possessed the lowest molecular weight and consisted of the highest amount of
      hydrophobic amino acid, which might be responsible for the antioxidant property
      of aged duck meat. The present findings provide an insight into the release of
      bioactive peptides in duck meat during post-mortem aging.

PMID- 28764015
TI  - Elicitation with methyl jasmonate supported by precursor feeding with
      phenylalanine: Effect on Garnacha grape phenolic content.
AB  - Recent works showed that elicitation, supported by precursor feeding, could be a
      strategy to increase phenolic content. However, these studies have never been
      conducted in viticulture. This strategy could be of greater interest in Garnacha,
      a grape variety characterized by its low phenolic content. Therefore, this work
      studied elicitation with methyl jasmonate (MeJ), supported by precursor feeding
      with phenylalanine (Phe), in order to improve Garnacha grape phenolic content.
      Results showed that Phe+MeJ treatment did not improve phenolic content to a
      greater extent than the corresponding individual treatments. Overall, the
      greatest improvement was obtained with MeJ application, followed by Phe+MeJ;
      while Phe treatment barely increased phenolic compounds. Consequently, it was not
      possible to confirm the hypothesis that elicitation by MeJ could be supported by
      precursor feeding with Phe, when both applied together. This is the first study
      dealing with this matter under field conditions serving as basis for future
      works.

PMID- 28764016
TI  - Electrodeposition of gold nanoparticles and reduced graphene oxide on an
      electrode for fast and sensitive determination of methylmercury in fish.
AB  - Fish consumption is the main source of methylmercury (CH3Hg+) exposure for
      humans. In this study, gold nanoparticles and reduced graphene oxide (AuNPs-RGO)
      modified electrode was fabricated for determination of CH3Hg+ in fish. The AuNPs
      RGO composite was synthesized by electroreduction method. The composite was
      characterized by scanning electron microscopy and energy dispersive spectra, X
      ray diffraction and Raman spectroscopy. Electrochemical performance of the
      proposed sensor was studied by cyclic voltammetry, electrochemical impedance
      spectroscopy and differential pulse stripping voltammetry. The excellent
      conductivity and large surface of graphene contributed to an improvement in the
      voltammetric stripping signal. Under the optimized conditions, the methylmercury
      concentration in the range from 3 to 24MUgL-1 had a good linear relation with the
      peak current. The detection limit of AuNPs-RGO modified electrode was 0.12MUgL-1.
      Finally, the developed electrode was applied to detect methylmercury in fish
      samples, and the obtained results were in good agreement with certified values.

PMID- 28764017
TI  - Chemical composition and biological activity of staghorn sumac (Rhus typhina).
AB  - Staghorn sumac (Rhus typhina) is native to North America, and has been used by
      indigenous peoples for food and non-food applications for a long time. It has
      been adapted to the other parts of the world for cultivation as a potential
      source of functional food ingredients. This review summarises the updated
      information on the chemical composition and diverse biological activities of
      staghorn sumac. Various factors affect the chemical composition, function
      retention during processing, and nutritional properties of staghorn sumac-derived
      products. These factors include botanical characteristics and environmental
      conditions, extraction and quantification methods, and processing parameters.
      Various innovative and potential uses of staghorn sumac in food, nutraceutical
      and cosmetic industries are suggested on the basis of the chemical constituents.
      This review provides a scientific basis for the development of staghorn sumac as
      a sustainable economic plant for food and other industries.

PMID- 28764018
TI  - Epoxyalkenal-trapping ability of phenolic compounds.
AB  - Lipid oxidation products have been shown to produce changes in food quality and
      safety as a consequence of carbonyl-amine reactions. Some of these reactions can
      be prevented by the use of phenolics, although the lipid-derived carbonyl
      trapping ability of phenolics is still poorly understood. In an attempt to fill
      this gap, the reactions of 4,5-epoxy-2-hexenal, 4,5-epoxy-2-heptenal, and 4,5
      epoxy-2-decenal, with 2-methylresorcinol and 2,5-dimethylresorcinol were studied.
      These reactions produced diverse 1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-2,7
      diols and 3,4,4a,9a-tetrahydro-1H-pyrano[3,4-b]benzofuran-3,7-diols, which were
      isolated and characterized by 1D and 2D nuclear magnetic resonance (NMR) and mass
      spectrometry (MS). The produced epoxyalkenal-phenol reaction was characterized
      and carbonyl-phenol adducts were produced firstly by epoxide-ring opening
      initiated by the attack of one phenolic hydroxyl group and, then, by addition of
      one aromatic phenol carbon to the carbon-carbon double bond of the epoxyalkenal.
      This reaction rapidly deactivated the most important reactive groups of
      epoxyalkenals, decreasing in this way their ability to modify amino compounds.

PMID- 28764019
TI  - Effects of in vitro digestion and in vitro colonic fermentation on stability and
      functional properties of yerba mate (Ilex paraguariensis A. St. Hil.) beverages.
AB  - Yerba mate (Ilex paraguariensis) is a plant that grows naturally in South
      America. From its leaves and thin stems different kinds of beverages are prepared
      (chimarrao, terere and tea mate), all of them rich in bioactive substances. The
      aim of this study was to evaluate the influence of in vitro gastrointestinal
      digestion and colonic fermentation on the stability of the polyphenols and on the
      antioxidant, antimicrobial and antitumoral activities of the yerba mate
      beverages. The phenolic chromatographic profile revealed that both the in vitro
      digestion and the colonic fermentation caused a pronounced decrease in 3,5-O
      dicaffeoylquinic acid and 5-O-caffeoylquinic acid in the preparations. However, 3
      O-caffeoylquinic acid, 4-O-caffeoylquinic acid and salvianolic acid I were only
      barely affected in all preparations. Despite the decrease in the phytochemicals
      content, yerba mate beverages maintain their functional properties such as
      antioxidant, antibacterial and antitumoral activities.

PMID- 28764020
TI  - Study of the repartition of phthalate esters during distillation of wine for
      spirit production.
AB  - Due to health concerns and legal matters, an investigation to limit phthalates
      esters (PEAs) in spirits is necessary. A lab still was used to perform pilot
      distillations according to the official method for brandy production in order to
      explore the repartition into the distilled fractions of each PAE. The process was
      divided in two steps: a premiere chauffe and a bonne chauffe. The former step
      included the cut into heads, heart and tails, while the latter into heads,
      brandy, secondes, and tails. The behaviour of each PAE during distillation was
      affected by its own chemical nature. Dibutyl phthalate (DBP) was entirely carried
      over into the distillate, while bis(2-ethylhexyl) phthalate (DEHP) only
      partially, and diisononyl phthalate (DINP) accumulated in the stillage. During
      the bonne chauffe, DBP and DEHP accumulated in the secondes more than in the
      brandy. A rectification step of the secondes was demonstrated to considerably
      reduce PAEs concentration.

PMID- 28764021
TI  - Optimization of anthocyanins extraction from black carrot pomace with
      thermosonication.
AB  - A study was conducted to identify optimal ultrasound processing conditions
      (ultrasound energy density and temperature) to maximize the extraction of
      anthocyanin colorants from black carrot pomace. The treatment maximized the yield
      of five different anthocyanin compounds from black carrot pomace with cyanidin-3
      xyloside-galactoside-glucoside-ferrulic acid (C3XGGF, 60.85-74.22mg/L) as the
      most abundant anthocyanin compound, followed by cyanidin-3-xyloside-galactoside
      (C3XG, 49.56-70.12mg/L). The response surface models predicted that if extraction
      conditions were conducted at 183.1J/g energy density and 50 degrees C, the yield
      of various anthocyanin compounds would be maximized from the black carrot pomace.
      Response surface models were developed correlating anthocyanin yield with
      ultrasonication treatment parameters. The study showed the synergy of combining
      ultrasonication and temperature for the extraction of anthocyanin pigments from
      black carrot pomace. Results of the study also further demonstrate the potential
      of ultrasonication technology as a tool for the extraction of valuable components
      waste products from fruits and vegetables juice industry.

PMID- 28764022
TI  - Fast gradient HPLC/MS separation of phenolics in green tea to monitor their
      degradation.
AB  - The degradation of catechins and other phenolics in green tea infusions were
      monitored using fast HPLC/MS separation. The final separation was performed
      within 2.5min using Ascentis Express C18 column (50mm*2.1mm i.d.) packed with
      2MUm porous shell particles. Degradation was studied in relation to the
      temperature of water (70, 80, 90 degrees C) and the standing time of the infusion
      (up to 6h). Along with chromatographic separation, the antioxidant properties of
      the infusions were monitored using two spectrophotometric methods. During staying
      of green tea infusion, the degradation of some catechins probably to gallic acid
      was observed. Finally, the influence of tea bag storage on antioxidant properties
      of green tea was evaluated. Rapid degradation of antioxidants after 3weeks was
      observed. The principal component analysis, factor analysis and discriminant
      analysis were used for the statistical evaluation of obtained experimental data.

PMID- 28764023
TI  - Preparation, antioxidant and antimicrobial evaluation of hydroxamated degraded
      polysaccharides from Enteromorpha prolifera.
AB  - In order to improve the antioxidant and antimicrobial abilities, hydroxamated
      degraded polysaccharides from Enteromorpha prolifera (HCDPE) were prepared from
      the corresponding carboxymethylated degraded polysaccharides (CDPE). HCDPE was
      characterized by FT-IR. The weight-average molecular weight of HCDPE was
      determined as 55.4kDa. The in vitro antioxidant activity of HCDPE was evaluated
      by determining the radical (1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl and
      superoxide anion radicals) scavenging abilities and total antioxidant activity.
      It was found that DPPH radical scavenging ability and total antioxidant activity
      of HCDPE were significantly improved compared to those of CDPE. The inhibitory
      effects of polysaccharides against the five bacterial strains (Bacillus subtilis,
      Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella spp.)
      were also evaluated by bacterial inhibition zone and minimum inhibitory
      concentration (MIC) assays. The results indicated that CDPE and HCDPE possess
      marked antimicrobial ability, while such an effect was not observed for the crude
      polysaccharides (PE) and the degraded polysaccharides (DPE).

PMID- 28764024
TI  - Does oolong tea (Camellia sinensis) made from a combination of leaf and stem
      smell more aromatic than leaf-only tea? Contribution of the stem to oolong tea
      aroma.
AB  - The raw materials used to make oolong tea (Camellia sinensis) are a combination
      of leaf and stem. Oolong tea made from leaf and stem is thought to have a more
      aromatic smell than leaf-only tea. However, there is no available evidence to
      support the viewpoint. In this study, sensory evaluation and detailed
      characterization of emitted and internal volatiles (not readily emitted, but
      stored in samples) of dry oolong teas and infusions indicated that the presence
      of stem did not significantly improve the total aroma characteristics. During the
      enzyme-active processes, volatile monoterpenes and theanine were accumulated more
      abundantly in stem than in leaf, while jasmine lactone, indole, and trans
      nerolidol were lower in stem than in leaf. Tissue-specific aroma-related gene
      expression and availability of precursors of aroma compounds resulted in
      different aroma distributions in leaf and stem. This study presents the first
      determination of the contribution of stem to oolong tea aroma.

PMID- 28764025
TI  - Variability in iron, zinc and phytic acid content in a worldwide collection of
      commercial durum wheat cultivars and the effect of reduced irrigation on these
      traits.
AB  - Diets very rich in cereals have been associated with micronutrient malnutrition,
      and the biofortification of them, has been proposed as one of the best approaches
      to alleviate the problem. Durum wheat is one of the main sources of calories and
      protein in many developing countries. In this study, 46 durum varieties grown
      under full and reduced irrigation, were analyzed for micronutrients and phytate
      content to determine the potential bioavailability of the micronutrients. The
      variation was 25.7-40.5mg/kg for iron and of 24.8-48.8mg/kg for zinc. For phytate
      determination (0.462-0.952 %), a modified methodology was validated in order to
      reduce testing costs while speeding up testing time. Variation was detected for
      phytate:iron and zinc molar ratios (12.1-29.6 and 16.9-23.6, respectively). The
      results could be useful to generate varieties with appropriate levels of phytate
      and micronutrients, which can lead to the development of varieties rich in
      micronutrients to overcome malnutrition.

PMID- 28764026
TI  - A simple and new reverse liquid-liquid microextraction for the automated
      spectrometric determination of doxycycline in chicken fat.
AB  - This work presents a new, simple and inexpensive reverse liquid-liquid
      microextraction of doxycycline (DOC) from chicken fat. In this just 13min
      extraction methodology, acidulated water, as extraction solvent (400uL), was
      used. A monochannel flow injection system was designed for the spectrometric
      determination of the analyte (y=344nm). The extracted solution containing DOC was
      loaded into the injection valve of the continuous flow manifold. A lineal range
      between 100 and 700ugDOCkg-1 sample was obtained. The LOD and LOQ were 33ugkg-1
      and 100ugkg-1 respectively. The relative standard deviation was 4.87% and the
      sample throughput for the entire process was 4.5h-1. As recovery values when the
      method was applied to real samples showed variability, the expanded uncertainties
      were calculated. Their values indicated that the new method is independent of the
      concentration of the analyte and the origin of the sample.

PMID- 28764027
TI  - Chain conformation, rheological and charge properties of fucoidan extracted from
      sea cucumber Thelenota ananas: A semi-flexible coil negative polyelectrolyte.
AB  - As a bioactive and functional polysaccharide, sea cucumber fucoidan has received
      increasing attention. Chain conformation and physicochemical properties of
      fucoidan extracted from Thelenota ananas (Ta-FUC) was investigated by utilizing
      HPSEC-MALLS-Visc-RI, microelectrophoresis and steady shear measurements. The
      conformation parameter alphas (0.61+/-0.02), the Mark-Houwink-Kuhn-Sakurada
      exponent alphaeta (0.92+/-0.01), alphah (0.64+/-0.01) and the Smidsrod-Haug
      stiffness parameter B (0.036+/-0.010) consistently manifested that Ta-FUC adopted
      a semi-flexible coil conformation in NaCl solution. Based on a wormlike cylinder
      model, stiffness parameters, including persistence length q (13.27+/-0.80nm) and
      cylinder diameter d (0.79nm), were calculated. This polysaccharide demonstrated
      shear-thinning rheological behaviour, and critical concentration from dilute to
      semidilute concentration regime was determined as 3.6mg/ml. Ta-FUC exhibited as a
      negative polyelectrolyte in wide pH and ionic strength ranges. These molecular
      characteristics and physicochemical properties would facilitate further
      application of Ta-FUC as a functional ingredient in food.

PMID- 28764028
TI  - Sensory evaluation of boar meat products by trained experts.
AB  - Rearing entire male pigs, one of the alternatives for surgical castration,
      entails the possible occurrence of boar taint. This study aimed at the
      investigation of the acceptability of meat from entire male pigs in 8 different
      meat products (cutlets, bacon, blade loin, tenderloin, dry fermented sausage,
      cooked ham, dry-cured ham and minced meat) by trained assessors. Generally, the
      sensory evaluation of meat samples was affected the most in the androstenone
      (AEON) group, indicating that AEON is the most offensive boar taint compound for
      sensitive assessors. Differences between the meat products showed the highest
      potential for processing tainted meat in cold meat products, which was most
      likely due to the serving temperature on the one hand and production-related
      influences on the other. However, more insights regarding reducing and masking
      effects of production-related factors on boar taint are necessary.

PMID- 28764029
TI  - Interaction of cinnamic acid and methyl cinnamate with bovine serum albumin: A
      thermodynamic approach.
AB  - Cinnamic acid (CA) and methyl cinnamate (MC) have attracted interest of
      researchers because of their broad therapeutic functions. Here, we investigated
      the interaction of CA and MC with bovine serum albumin (BSA) at pH 3.5, 5.0, and
      7.4 using fluorescence spectroscopy, differential scanning nanocalorimetry, and
      measurements of interfacial tension, size, and zeta potential. BSA formed a
      complex with the ligands with stoichiometry of approximately 1.0. At pH 7.4, CA
      BSA complex formation was entropically driven. The interaction between MC and BSA
      was more favorable than with CA and was enthalpically driven under the same
      conditions. The pH played an important role in BSA conformation, which altered
      the manner in which it interacts with the ligands. Interestingly, both CA and MC
      had no effect on the surface tension of BSA/air interfaces. These data contribute
      to the knowledge of CA/MC-BSA interactions and provide important data for
      application in the food industry.

PMID- 28764030
TI  - Experimental and computational study of guanidinoacetic acid self-aggregation in
      aqueous solution.
AB  - In this work for the first time the physicochemical and thermal properties of
      guanidinoacetic acid (GAA) and its aqueous solutions have been performed to test
      for its viability as a potential dietary supplement. Thermal stability,
      viscosity, solubility and experimental density are determined. From measured
      densities the volumetric properties were estimated and discussed in the scope of
      GAA self-aggregation in aqueous solutions using experimental and computational
      results. Based on thermal stability and solubility measurements, it is found that
      GAA is more thermally stable but less soluble comparing to creatine due to a self
      aggregation process that occurs at GAA concentrations higher than 0.013mol.dm-3.
      Existence of self-aggregation influences the macroscopic properties of aqueous
      GAA solutions, but also its bioavailability.

PMID- 28764031
TI  - Encapsulation of ferulic acid ethyl ester in caseinate to suppress off-flavor
      formation in UHT milk.
AB  - Phenolic compounds can principally suppress the off-flavor development in
      ultrahigh temperature (UHT) treated milk, but little has been studied for
      lipophilic phenolic compounds that are to be encapsulated for even distribution
      in milk. The objective of this work was to study physicochemical properties of
      ferulic acid ethyl ester (FAEE) encapsulated in sodium caseinate and the
      inhibition of volatile formation after UHT processing. The capsules had an
      average hydrodynamic diameter of 246.2+/-10.9nm, a polydispersity index of 0.26+/
      0.01, and a zeta-potential of -31.72+/-0.74mV. The capsules and the encapsulated
      FAEE were stable after heating at 138 degrees C for 16min and UV radiation at
      365nm for 32h. The encapsulated FAEE at a level of 0.18-1.42mg/mL suppressed the
      formation of 2-acetyl-2-thiazoline in model UHT milk by 32.8-63.2% after 30-day
      storage at 30 degrees C. Therefore, FAEE encapsulated in caseinate can be
      potentially used to improve the quality of UHT milk.

PMID- 28764032
TI  - Phenolic acids and flavonoids of peanut by-products: Antioxidant capacity and
      antimicrobial effects.
AB  - Peanut skin (PS) and meal from dry-blanched peanuts (MDBP) were evaluated as
      sources of phenolic compounds. PS rendered the highest total phenolic content,
      antioxidant capacity towards ABTS radical cation, DPPH and hydroxyl radicals as
      well as reducing power. Phenolic acids were present in PS and MDBP whereas
      proanthocyanidins and monomeric flavonoids were found only in PS as identified by
      HPLC-DAD-ESI-MSn. Procyanidin-rich extracts prevented oxidation in non-irradiated
      and gamma-irradiated fish model system. Both extracts inhibited the growth of
      gram-positive (Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes,
      Geobacillus stearothermophilus) and gram-negative bacteria (Pseudomonas
      aeruginosa, Pseudomonas fluorescens, Salmonella Enteritidis, Salmonella
      Typhimurium, Escherichia coli). Regardless of the strain, phenolic acid-rich
      extracts showed the lowest minimum inhibitory capacity (MIC); therefore
      presenting higher antibacterial effect. The MIC of phenolic acid-rich extracts
      (24-49MUgphenolics/mL) was higher but comparable to Ampicillin (10MUg/mL). Thus,
      phenolics in PS and MDBP may serve as antioxidants and antimicrobial compounds.

PMID- 28764033
TI  - Genetic and geochemical signatures to prevent frauds and counterfeit of high
      quality asparagus and pistachio.
AB  - A fingerprinting strategy based on genetic (simple sequence repeat) and
      geochemical (multielement and 87Sr/86Sr ratio) analysis was tested to prove the
      geographical origin of high-quality Italian products "White Asparagus from
      Bassano del Grappa" and "Green Pistachio from Bronte". Genetic analysis generated
      many polymorphic alleles and different specific amplified fragments in both
      agriproducts. In addition, a core set of markers was defined. According to
      variability within production soils and products, potential candidate elements
      linking asparagus (Zn, P, Cr, Mg, B, K) and pistachio (Mn, P, Cr, Mg, Ti, B, K,
      Sc, S) to the production areas were identified. The Sr isotopic signature was an
      excellent marker when Italian asparagus was compared with literature data for
      Hungarian and Peruvian asparagus. This work reinforces the use of Sr isotope
      composition in the soil bioavailable fraction, as assessed by 1mol/L NH4NO3, to
      distinguish white asparagus and pistachio originating from different geographical
      areas.

PMID- 28764034
TI  - Shelf-life extension of semi-dried buckwheat noodles by the combination of
      aqueous ozone treatment and modified atmosphere packaging.
AB  - The present study investigated the combined effects of aqueous ozone treatment
      and modified atmosphere packaging (MAP) on prolonging the shelf-life of semi
      dried buckwheat noodles [SBWN; moisture content (22.5+/-0.5%)] at 25 degrees C.
      Firstly, the different concentrations of ozonated water were used to make SBWN.
      Subsequently, SBWN prepared with ozonated water were packaged under six different
      conditions and stored for 11days. Changes in microbial, chemical-physical,
      textural properties and sensorial qualities of SWBN were monitored during
      storage. Microbiological results indicated that adopting 2.21mg/L of ozonated
      water resulted in a 1.8 log10 CFU/g reduction of the initial microbial loads in
      SBWN. In addition, MAP suppressed the microbial growth with a concomitant
      reduction in the rates of acidification and quality deteriorations of SBWN.
      Finally, the shelf-life of sample packed under N2:CO2=30:70 was extended to
      9days, meanwhile textural and sensorial characteristics were maintained during
      the whole storage period.

PMID- 28764035
TI  - Resveratrol: A thermoanalytical study.
AB  - Resveratrol is a natural polyphenol found in various plants, mainly in the bark
      of the red grapes. It has been widely studied due to its antioxidant, anti
      inflammatory, anticancer and anti-aging properties. The thermal behavior of
      resveratrol was investigated by using simultaneous thermogravimetry and
      differential scanning calorimetry (TG-DSC), evolved gas analysis (TG-DSC-FTIR)
      and High-resolution mass spectra (HRMS). The results provided information
      concerning the thermal stability, thermal decomposition, identification of the
      main gaseous products evolved and intermediate compounds formed during the
      thermal decomposition.

PMID- 28764036
TI  - High resolution mass spectrometry studies of sulforaphane and indole-3-carbinol
      in broccoli.
AB  - Broccoli is a rich source of bioactive compounds. Among them, sulforaphane and
      indole-3-carbinol have attracted a lot of attention, since their consumption is
      associated with reduced risk of cancer. In this work, the development of an
      efficient and direct method for the simultaneous determination of sulforaphane
      and indole-3-carbinol in broccoli using UPLC-HRMS/MS is described. The
      correlation coefficient, and limits of detection (LOD) and quantification (LOQ)
      were 0.993, 0.77mg/L and 2.35mg/L for sulforaphane and 0.997, 0.42mg/L, 1.29mg/L
      for indole-3-carbinol, respectively. The content of sulforaphane and indole-3
      carbinol varied between 72+/-9-304+/-2mg and 77+/-1-117+/-3mg per 100g of fresh
      florets, respectively. Taking into consideration the differences in cultivar,
      geography, season and environmental factors, the results agreed with values
      published in the literature using other techniques.

PMID- 28764037
TI  - Antioxidant action of fermented grain food supplement: Scavenging of peroxyl
      radicals and inhibition of plasma lipid oxidation induced by multiple oxidants.
AB  - Unregulated oxidative modification of biological molecules induced by multiple
      oxidants in vivo has been implicated in the pathogenesis of various diseases.
      Accordingly, the role of antioxidants contained in foods in the maintenance of
      health and prevention of diseases has received much attention. The efficacy of
      antioxidants against oxidative stress depends on the nature of oxidants. In the
      present study, the antioxidant action of fermented grain food supplement,
      Antioxidant Biofactor (AOB), for scavenging peroxyl radical and inhibition of
      plasma lipid oxidation induced by multiple oxidants was measured. The antioxidant
      efficacy against lipid oxidation was assessed by the level of lipid
      hydroperoxides produced using diphenyl-1-pyrenylphosphine, which is not
      fluorescent per se but reacts with lipid hydroperoxides stoichiometrically to
      yield highly fluorescent diphenyl-1-pyrenylphosphine oxide. AOB acted as a potent
      peroxyl radical scavenger and suppressed lipid oxidation induced by peroxyl
      radical, peroxynitrite, hypochlorite, and singlet oxygen, but not by 15
      lipoxygenase.

PMID- 28764038
TI  - Dietary acrylamide: What happens during digestion.
AB  - Acrylamide is a well-known potentially carcinogen compound formed during thermal
      processing as an intermediate of Maillard reactions. Three objectives were
      addressed: the impact of gastric digestion on acrylamide content of French Fries,
      chips, chicken nuggets, onions rings, breakfast cereals, biscuits, crackers,
      instant coffee and coffee substitute; the acrylamide content evolution during
      gastrointestinal digestion of French fries and chips; and the effectiveness of
      blanching and air-frying on acrylamide mitigation after gastrointestinal
      digestion. A significant increase (p-value <0.05) in acrylamide content was
      observed for most of the products after gastric digestion (maximum registered for
      sweet biscuits, from 30+/-8 to 150+/-48ug/kg). However, at the end of the
      intestinal stage, acrylamide values were statistically similar (p-value=0.132)
      for French fries and lower than the initial values (before digestion) in potato
      chips (p-value=0.027). Finally, the low acrylamide content found in blanched and
      air-fried samples, remained still lower than for deep fried samples even after
      gastrointestinal digestion.

PMID- 28764039
TI  - Physicochemical properties of oils extracted from gamma-irradiated Sacha Inchi
      (Plukenetia volubilis L.) seeds.
AB  - This study evaluated the physicochemical properties of oils extracted from gamma
      irradiated Sacha Inchi (Plukenetia volubilis L.) seeds (SIS) at four different
      doses (0, 1, 5 and 8kGy). Fatty acid composition, tocopherol content, FTIR
      spectra, density, refractive index, acidity, peroxide value (PV), p-anisidine
      index (p-An), oxidation induction period (IP), and color were chosen as test
      parameters. Overall, the irradiation treatment did not significantly affect the
      physicochemical properties of the Sacha Inchi oils, although slight increases
      were found in the PV and p-An, as the irradiation dose increased. gamma
      Irradiation led to a decrease in the concentration of gamma- and delta
      tocopherol, as well as in the IP. However, according to the FTIR analyses, the
      functional groups of the oils were not significantly affected by the gamma
      irradiation. These results suggest that gamma-irradiation at 1-5kGy, might be
      recommended as a suitable eco-friendly technology for the preservation of SIS
      used for oil production.

PMID- 28764040
TI  - Quantitative analysis of species specificity of two anti-parvalbumin antibodies
      for detecting southern hemisphere fish species demonstrating strong phylogenetic
      association.
AB  - This study aimed to develop a novel approach to determine the correlation between
      the parvalbumin (PAV) contents and their corresponding immunoreactivity
      (detectability) in southern hemisphere fish species. The immuno-detected PAV
      contents of the test fish species were estimated by a quantitative SDS-PAGE. A
      quantitative Enzyme-Linked ImmunoSorbent Assay (ELISA) was formatted to assess
      relative immunoreactivity of PAV. Sixteen species (forty-three percent) displayed
      a positive correlation with the anti-cod PAV polyclonal antibody, but no
      correlation with the anti-carp PAV monoclonal antibody. There was a strong
      phylogenetic association of the PAV immunoreactivity. Species from the order of
      Perciformes showed strong binding with both antibodies; whereas species from
      Salmoniformes, Ophidiiformes, Scombriformes, Scorpaeniformes, and
      Tetraodontiformes showed weak or no binding. This approach showed for the first
      time a statistical correlation between the PAV content and the immunoreactivity
      and allowed to rank the relative species/order specificity of the two antibodies
      for the southern hemisphere fish PAV.

PMID- 28764041
TI  - Monitoring the progression of calcium and protein solubilisation as affected by
      calcium chelators during small-scale manufacture of casein-based food matrices.
AB  - Calcium and protein solubilisation during small-scale manufacture of semi-solid
      casein-based food matrices was investigated and found to be very different in the
      presence or absence of calcium chelating salts. Calcium concentrations in the
      dispersed phase increased and calcium-ion activity (ACa++) decreased during
      manufacture of the matrices containing calcium chelating salts; with ~23% of
      total calcium solubilised by the end of manufacture. In the absence of calcium
      chelating salts, these concentrations were significantly lower at equivalent
      processing times and remained unchanged as did ACa++, throughout manufacture. The
      protein content of the dispersed phase was low (<=3% of total protein), but was
      significantly higher for matrices containing calcium chelating salts. This study
      elucidates the critical role of calcium chelating salts in modulating casein
      hydration and dispersion and gives an indication of the levels of soluble calcium
      and protein required to allow matrix formation during manufacture of casein-based
      food structures e.g. processed and analogue cheese.

PMID- 28764042
TI  - Enzymatic production of dietary nucleotides from low-soluble purine bases by an
      efficient, thermostable and alkali-tolerant biocatalyst.
AB  - Traditionally, enzymatic synthesis of nucleoside-5'-monophosphates (5'-NMPs)
      using low water-soluble purine bases has been described as less efficient due to
      their low solubility in aqueous media. The use of enzymes from extremophiles,
      such as thermophiles or alkaliphiles, offers the potential to increase
      solubilisation of these bases by employing high temperatures or alkaline pH. This
      study describes the cloning, expression and purification of hypoxanthine-guanine
      xanthine phosphoribosyltransferase from Thermus thermophilus (TtHGXPRT).
      Biochemical characterization indicates TtHGXPRT as a homotetramer with excellent
      activity and stability across a broad range of temperatures (50-90 degrees C) and
      ionic strengths (0-500mMNaCl), but it also reveals an unusually high activity and
      stability under alkaline conditions (pH range 8-11). In order to explore the
      potential of TtHGXPRT as an industrial biocatalyst, enzymatic production of
      several dietary 5'-NMPs, such as 5'-GMP and 5'-IMP, was carried out at high
      concentrations of guanine and hypoxanthine.

PMID- 28764043
TI  - Characterization of carotenoid profile of Spanish Sanguinos and Verdal prickly
      pear (Opuntia ficus-indica, spp.) tissues.
AB  - Carotenoid profiles of different tissues (peel, pulp and whole fruit) of Spanish
      Sanguinos (red) and Verdal (orange) prickly pears (Opuntia ficus-indica spp.)
      have been characterized in detail and quantified for the first time. Carotenoids
      were determined by HPLC-PDA-MS (APCI+), using a reverse phase C30 column. A total
      of 9 xantophylls and 4 hydrocarbon carotenes were identified. Also, minor amounts
      of chlorophyll a, a' and b can be observed in Opuntia peel extracts. All
      carotenoids were found to be present in their free form (no carotenoid esters
      were detected). The RAE was highest in Opuntia peels, showing values from 19.20
      to 16.48ug/100g fresh weigth, for Sanguinos and Verdal Opuntia fruits,
      respectively. The main carotenoid in Opuntia peel extracts was (all-E)-lutein
      with 1132.51 and 767.98ug/100g fresh weigth, followed by (all-E)-beta-carotene
      with 200.40 and 173.50ug/100g fresh weigth for Sanguinos and Verdal varieties of
      Opuntia fruits, respectively.

PMID- 28764044
TI  - Encapsulation of antioxidant phenolic compounds extracted from spent coffee
      grounds by freeze-drying and spray-drying using different coating materials.
AB  - Freeze-drying and spray-drying techniques were evaluated for encapsulation of
      phenolic compounds (PC) extracted from spent coffee grounds. Additionally, the
      use of maltodextrin, gum arabic and a mixture of these components (ratio 1:1) as
      wall material to retain the PC and preserve their antioxidant activity was also
      assessed. The contents of PC and flavonoids (FLA), as well as the antioxidant
      activity of the encapsulated samples were determined in order to verify the
      efficiency of each studied condition. Additional analyses for characterization of
      the samples were also performed. Both the technique and the coating material
      greatly influenced the encapsulation of antioxidant PC. The best results were
      achieved when PC were encapsulated by freeze-drying using maltodextrin as wall
      material. Under these conditions, the amount of PC and FLA retained in the
      encapsulated sample corresponded to 62% and 73%, respectively, and 73-86% of the
      antioxidant activity present in the original extract was preserved.

PMID- 28764045
TI  - Pulsed light inactivation of horseradish peroxidase and associated structural
      changes.
AB  - Pulsed light (PL) is a non-thermal preservation method in which foods are
      subjected to one or several intense pulses of wide-spectrum light. Peroxidase
      (POD) is an enzyme that needs to be inactivated or inhibited because of its
      deleterious effects on the quality of fruits and vegetables. The feasibility of
      using PL to inactivate POD was tested and results explained based on measurements
      of UV-vis spectrum, far-UV circular dichroism and tryptophan fluorescence, and
      the phase-diagram method. PL reduced the activity of POD by more than 95% after
      applying 128Jcm-2. There was observed a decrease in the Reinheitzahl value and
      ellipticity and an increase in tryptophan fluorescence at incremental fluences,
      as well as linear phase diagrams. The study indicates that the inactivation of
      POD by PL is an all-or-none process related to loss of helical structure, weak
      unfolding and ejection of the prostetic group.

PMID- 28764046
TI  - Stability of bioactive compounds in butia (Butia odorata) fruit pulp and nectar.
AB  - Butia odorata is a palm tree native to southern Brazil whose fruit (known as
      butia) and leaves are used to make many food products and crafts. Butia contain
      several biologically active compounds with potential health benefits. However,
      processing conditions can alter quality attributes including bioactive compound
      content. This study evaluated the stability of bioactive compounds in butia pulp
      upon pasteurization, during 12months of frozen storage, and in butia nectar after
      a 3-month storage period. Pulp pasteurization resulted in a reduction in
      phenolic, flavonoid, carotenoid, and ascorbic acid contents. After a 12-month
      frozen storage period, flavonoid, phenolic, and ascorbic acid contents decreased
      while carotenoid content remained unaltered. Carotenoid, ascorbic acid, and
      phenolic contents were unaffected by the 3-month storage of butia nectar;
      however, flavonoid content and antioxidant potential were reduced. Despite
      bioactive compound degradation upon heat treatment and storage, butia nectar
      remained rich in phenolics, especially (-)-epicatechin, rutin, and (+)-catechin.

PMID- 28764047
TI  - An integrated antioxidant activity fingerprint for commercial teas based on their
      capacities to scavenge reactive oxygen species.
AB  - An integrated antioxidant activity fingerprint, based on on-line screening
      methods for three reactive oxygen species (ROS: superoxide anion radical,
      hydrogen peroxide, and hydroxyl radical) was developed to comprehensively
      evaluate the quality of 12 batches of commercial tea. High-performance liquid
      chromatography (HPLC) coupled with a chemiluminescent detector was used to
      determine the antioxidant characteristics of a selection of teas as bioactivity
      fingerprints. An HPLC-electrospray ionization-mass spectrometry analysis was used
      to determine the chemical profiles of the teas in the chromatographic
      fingerprints. All of the green teas (S01-S08) were better scavengers of the three
      ROS compared to the oolong teas (S09-S12). The main scavengers of the three ROS
      in green tea were 5-galloylquinic acid, (-)-epigallocatechin-3-O-gallate, and (-)
      epicatechin-3-O-gallate, whereas in oolong tea, they were (-)-epigallocatechin-3
      O-gallate and (-)-epigallocatechin. This study demonstrates that comprehensive
      fingerprinting is a potentially meaningful method for evaluating the quality of
      food products.

PMID- 28764048
TI  - Effect of lentil proteins isolate concentration on the formation, stability and
      rheological behavior of oil-in-water nanoemulsions.
AB  - The formation, stability and rheology of 5wt% oil-in-water nanoemulsions as a
      function of lentil protein isolate concentration (0.5-5wt%) at pH 3.0 was
      investigated for 28days. All nanoemulsions, except 1wt% protein, showed bimodal
      droplet size distribution where the larger diameter peak was ascribed to protein
      aggregates and entrapped oil droplets. The average droplet size for all
      nanoemulsions measured from the lower diameter peak ranged from 161 to 357nm,
      which did not change over 28days. Stable flowable nanoemulsions were formed at 1
      2wt% protein concentrations. Nanoemulsions with 3 and 5wt% protein formed strong
      non-flowable gels which showed a two-step yielding behavior during strain-sweep
      rheology, indicating gel formation by interconnected clusters of proteins and oil
      droplets. This study demonstrated that lentil protein has a potential to be
      utilized as an emulsifier in nanoemulsions, as well as in the formation of
      emulsion gels at higher protein concentrations.

PMID- 28764049
TI  - Synthesis of alpha-linolenic acid-rich triacylglycerol using a newly prepared
      immobilized lipase.
AB  - An alpha-linolenic acid (ALA)-rich triacylglycerol (TAG) was synthesized from an
      ALA-rich fatty acid (FA) from perilla oil and glycerol, using a newly prepared
      immobilized lipase under vacuum. The ALA-rich FA (purity >90wt%) used as the
      substrate was prepared by urea complexation from perilla oil FAs. Liquid Lipozyme
      TL 100L lipase from Thermomyces lanuginosus was used for immobilization. Nine
      different hydrophilic and hydrophobic carriers for immobilization were tested,
      and Duolite A568, which is a hydrophilic resin, was selected as the best carrier.
      This immobilized lipase was used to synthesize TAG by direct esterification under
      vacuum. The parameters investigated were temperature, enzyme loading, and vacuum
      level. The optimum reaction conditions were a temperature of 60 degrees C, an
      enzyme loading of 15% (based on the total weight of the substrate), and a vacuum
      of 0.7kPa, respectively. The maximum conversion to TAG of ca. 88wt% was obtained
      in 12h under the optimum conditions.

PMID- 28764050
TI  - Profiling and quantification of regioisomeric caffeoyl glucoses in Solanaceae
      vegetables.
AB  - Based on the recently developed tandem MS based hierarchical scheme for the
      identification of regioisomeric caffeoyl glucoses, selected vegetables were
      profiled with respect to their caffeoyl glucose content. The dietary plants
      profiled were tomato, pepper, chilli and aubergine, all members of the Solanaceae
      family. 6-O-caffeoyl glucose was found to be the predominant isomer. In processed
      food such as tomato puree and ketchup a larger number of caffeoyl-glucose isomers
      formed through acyl migration reactions were observed. A LC-MS based quantitative
      method was developed, validated and caffeoyl glucose regioisomers quantified for
      the first time in dietary plants with quantitative data obtained from
      representative 30 food samples.

PMID- 28764051
TI  - Investigation of solubility of carbon dioxide in anhydrous milk fat by lab-scale
      manometric method.
AB  - This study aims to examine the solubility of CO2 in anhydrous milk fat (AMF) as
      functions of partial pressure, temperature, chemical composition and physical
      state of AMF. AMF was fractionated at 21 degrees C to obtain stearin and olein
      fractions. The CO2 solubility was measured using a home-made experimental
      apparatus based on changes of CO2 partial pressures. The apparatus was found to
      be reliable as the measured and theoretical values based on the ideal gas law
      were comparable. The dissolved CO2 concentration in AMF increased with an
      increase in CO2 partial pressure (0-101kPa). The apparent CO2 solubility
      coefficients (molkg-1Pa-1) in the AMF were 5.75+/-0.16*10-7, 3.9+/-0.19*10-7 and
      1.19+/-0.14*10-7 at 35, 24 and 4 degrees C, respectively. Higher liquid oil
      proportions resulted in higher CO2 solubility in the AMF. There was insignificant
      difference in the dissolved CO2 concentration among the AMF, stearin and olein
      fractions in their liquid state at 40 degrees C.

PMID- 28764052
TI  - Flavour production by Saprochaete and Geotrichum yeasts and their close
      relatives.
AB  - In this study, a total of 30 yeast strains belonging to the genera Dipodascus,
      Galactomyces, Geotrichum, Magnusiomyces and Saprochaete were investigated for
      volatile organic compound production using HS-SPME-GC/MS analysis. The resulting
      flavour profiles, including 36 esters and 6 alcohols compounds, were
      statistically evaluated by cluster and PCA analysis. Two main groups of strains
      were extracted from this analysis, namely a group with a low ability to produce
      flavour and a group producing mainly alcohols. Two other minor groups of strains
      including Saprochaete suaveolens, Geotrichum marinum and Saprochaete gigas were
      diverging significantly from the main groups precisely because they showed a good
      ability to produce a large diversity of esters. In particular, we found that the
      Saprochaete genus (and their closed relatives) was characterized by a high
      production of unsaturated esters arising from partial catabolism of branched
      chain amino-acids. These esters were produced by eight phylogenetically related
      strains of Saprochaete genus.

PMID- 28764053
TI  - Modulating conversion of isoflavone glycosides to aglycones using crude beta
      glycosidase extracts from almonds and processed soy.
AB  - Food processing alters the physicochemical state of soy which can enhance
      chemical and enzymatic conversion of isoflavones to their aglycone forms. This
      study investigated the role of beta-glycosidase from processed soy-ingredient
      mixture (SIM) or almonds, and examined the impact of isoflavone composition in
      mediating conversion to aglycones. beta-Glycosidase activity was quantified using
      p-nitrophenol-beta-d-glucopyranoside and SIM isoflavone extracts. Almond beta
      glycosidase activity was significantly (p<0.001) reduced after roasting (99%
      reduction) or steaming (97% reduction) compared to raw almonds. SIM beta
      glycosidase activity, however, increased, with steaming by 66% (p<0.001) and with
      roasting by 52% (p=0.022), compared to raw SIM. After incubation with beta
      glycosidase, percentage of aglycone (total aglycone/total isoflavones) in SIM
      isoflavone extracts increased significantly in raw (35%), fermented (48%),
      roasted (88%) and steamed (91%) SIM, compared to their initial (~5%)
      compositions. Manipulation of beta-glycosidase activity and isoflavone
      composition can be used to modulate aglycone content in soy food products.

PMID- 28764054
TI  - Seed incorporation during vinification and its impact on chemical and
      organoleptic properties in Syzygium cumini wine.
AB  - Syzgium cumini (Jamun) is an evergreen tropical tree, its various parts are known
      for many therapeutic properties. The present work represents the production of
      wines from jamun fruits using two different native isolates (Saccharomyces
      cerevisiae - KF551990 and Pichia gummiguttae - MCC 1273) and influence of jamun
      seeds on the physico-chemical parameters, chromatic properties, phenolic
      components and sensory attributes of wine. Wine produced was bottle aged for one
      year. On aging there was a reduction in bitterness and astringency. Aging lead to
      reduction in monomeric anthocyanin with an increase in co-pigmented and polymeric
      anthocynins thus affecting the wine color. Anthocyanin analysis in jamun wine
      indicated petunidin 3,5-diglucoside as the principal anthocyanin. PCA analysis of
      wine revealed association of young jamun wine with anthocyanin components. PLS
      analysis exhibited both positive and negative correlation between various
      attributes indicating sensory perception of jamun wine is affected by overall
      composition of the wine.

PMID- 28764055
TI  - Anthocyanin biosynthesis and accumulation in blood oranges during postharvest
      storage at different low temperatures.
AB  - Blood oranges require low temperature for anthocyanin production. We have
      investigated the activation of anthocyanin biosynthesis and accumulation in the
      pulp of Moro blood and Pera blond oranges (Citrus sinensis L. Osbeck) stored at
      either 4 or 9 degrees C after harvesting. Both temperatures stimulated
      anthocyanin accumulation in blood but not in blond oranges. Nonetheless, blood
      orange fruits stored at 9 degrees C reached a darker purple coloration, higher
      anthocyanin contents and enhanced upregulation of genes from the flavonoid
      pathway in the pulp and juice than those kept at 4 degrees C. Our results
      indicated that dihydroflavonol channeling toward anthocyanin production was
      boosted during the storage at 9 degrees C compared to 4 degrees C, providing more
      leucoanthocyanidins to enzymes downstream in the pathway. Finally, despite both
      low temperatures stimulated the expression of key transcription factors likely
      regulating the pathway, their expression profiles could not explain the
      differences observed at 9 and 4 degrees C.

PMID- 28764056
TI  - Species identification in meat products: A new screening method based on high
      resolution melting analysis of cyt b gene.
AB  - Meat adulteration by substitution with lower value products and/or mislabeling
      involves economic, health, quality and socio-religious issues. Therefore,
      identification and traceability of meat species has become an important subject
      to detect possible fraudulent practices. In the present study the development of
      a high resolution melt (HRM) screening method for the identification of eight
      common meat species is reported. Samples from Bos taurus, Ovis aries, Sus scrofa
      domestica, Equus caballus, Oryctolagus cuniculus, Gallus gallus domesticus,
      Meleagris gallopavo and Coturnix coturnix were analyzed through the amplification
      of a 148 bp fragment from the cyt b gene with a universal primer pair in HRM
      analyses. Melting profiles from each species, as well as from several DNA
      mixtures of these species and blind samples, allowed a successful species
      differentiation. The results demonstrated that the HRM method here proposed is a
      fast, reliable, and low-cost screening technique.

PMID- 28764057
TI  - Zirconium-based highly porous metal-organic framework (MOF-545) as an efficient
      adsorbent for vortex assisted-solid phase extraction of lead from cereal,
      beverage and water samples.
AB  - In this study, zirconium-based highly porous metal-organic framework, MOF-545,
      was synthesized and characterized. The surface area of MOF-545 was found to be
      2192m2/g. This adsorbent was used for the first time as an adsorbent for the
      vortex assisted-solid phase extraction of Pb(II) from cereal, beverage and water
      samples. Lead in solutions was determined by FAAS. The optimal experimental
      conditions were as follows: the amount of MOF-545, 10mg; pH of sample, 7;
      adsorption and elution time, 15min; and elution solvent, 2mL of 1molL-1HCl. Under
      the optimal conditions of the method, the limit of detection, preconcentration
      factor and precision as RSD% were found to be 1.78MUgL-1, 125 and 2.6%,
      respectively. The adsorption capacity of the adsorbent for lead was found to be
      73mgg-1. The method was successfully verified by analyzing two certified
      reference materials (BCR-482 Lichen and SPS-WW1 Batch 114) and spiked chickpea,
      bean, wheat, lentil, cherry juice, mineral water, well water and wastewater
      samples.

PMID- 28764058
TI  - Effect of polishing on glycemic index and antioxidant properties of red and white
      basmati rice.
AB  - Four different pigmented dark-red (red) and non-pigmented white basmati rice
      varieties were tested for their nutrient composition, glycemic index (GI), total
      phenolic content (TPC), total anthocyanin content (TAC) and antioxidant activity
      (AOA) at 10% and 100% polished levels. The red basmati had higher content of ash,
      protein, fat, TPC, TAC and AOA than white basmati. Red and white basmati
      varieties can be classified as low GI and medium GI rice, respectively. The
      degree of polishing had no effect on the GI. However, there was a significant
      negative correlation (r>-0.81; P<0.01) between GI value with amylose, crude
      fiber, crude fat, crude protein, ash, AOA, TPC and TAC contents of basmati.
      Relatively higher levels of TPC, TAC and AOA were found in red basmati than white
      basmati varieties. Therefore, red basmati varieties can serve as low GI sources
      of functional food.

PMID- 28764059
TI  - A two-step enzymatic modification method to reduce immuno-reactivity of milk
      proteins.
AB  - A two-step enzymatic approach to reduce immuno-reactivity of whey protein isolate
      and casein has been studied. The method involves partial hydrolysis of proteins
      with proteases, followed by repolymerization with microbial transglutaminase.
      Whey protein isolate partially hydrolyzed with chymotrypsin, trypsin, or
      thermolysin retained about 80%, 30%, and 20% of the original immuno-reactivity,
      respectively. Upon repolymerization the immuno-reactivity decreased to 45%, 35%,
      and 5%, respectively. The immuno-reactivity of hydrolyzed and repolymerized
      casein was negligible compared to native casein. The repolymerized products were
      partially resistant to in vitro digestion. Peptides released during digestion of
      repolymerized thermolysin-whey protein hydrolysate had less than 5% immuno
      reactivity, whereas those of whey protein control exhibited a sinusoidal immuno
      reactivity ranging from 5 to 20%. Peptides released during digestion of
      repolymerized thermolysin-casein hydrolysates had no immuno-reactivity. These
      results indicated that it is possible to produce hypoallergenic milk protein
      products using the two-step enzymatic modification method involving thermolysin
      and transglutaminase.

PMID- 28764060
TI  - Determination of starting materials, intermediates, and subsidiary colors in the
      color additive Food Red No. 106 (Sulforhodamine B) using high-performance liquid
      chromatography.
AB  - The main subsidiary color of structure in Food Red No. 106 (R106) was identified
      to be a desethyl derivative (R106-SubA). High-performance liquid chromatography
      (HPLC) was performed for the quantitative determination of benzaldehyde-2,4
      disulfonic acid, N,N-diethyl-m-aminophenol, leuco acid, pyrone acid, R106-SubA,
      etc. in R106. An ammonium acetate solution (20mM) and acetonitrile:water (7:3)
      were used to stabilize the retention time of the HPLC analytes. The linearity of
      the calibration curves was in the range of 0.05-10MUg/mL, with good correlation
      coefficients (R2>0.9983). The recoveries of impurities at levels 0.1%, 0.5% and
      1% ranged from 94.2% to 106.6% with relative standard deviations of 0.1%-1.0%.
      While surveying commercial R106, the amounts obtained by area% determination were
      similar to those obtained by the calibration-curve determination. The area%
      determination by HPLC for the determinations of impurities in R106 is a simple
      and reliable method and can be applied in routine analysis.

PMID- 28764061
TI  - Geographical origin discrimination of lentils (Lens culinaris Medik.) using 1H
      NMR fingerprinting and multivariate statistical analyses.
AB  - Lentil samples coming from two different countries, i.e. Italy and Canada, were
      analysed using untargeted 1H NMR fingerprinting in combination with chemometrics
      in order to build models able to classify them according to their geographical
      origin. For such aim, Soft Independent Modelling of Class Analogy (SIMCA), k
      Nearest Neighbor (k-NN), Principal Component Analysis followed by Linear
      Discriminant Analysis (PCA-LDA) and Partial Least Squares-Discriminant Analysis
      (PLS-DA) were applied to the NMR data and the results were compared. The best
      combination of average recognition (100%) and cross-validation prediction
      abilities (96.7%) was obtained for the PCA-LDA. All the statistical models were
      validated both by using a test set and by carrying out a Monte Carlo Cross
      Validation: the obtained performances were found to be satisfying for all the
      models, with prediction abilities higher than 95% demonstrating the suitability
      of the developed methods. Finally, the metabolites that mostly contributed to the
      lentil discrimination were indicated.

PMID- 28764062
TI  - Effect of reactive oxygen species on quality maintenance of broccoli florets with
      electrostatic atomized water particle treatment.
AB  - The effect of electrostatic atomized water particle (EAWP) treatment on quality
      maintenance during postharvest storage was determined to clarify a physiological
      role of reactive oxygen species in broccoli florets. The EAWP treatment
      suppressed the floret yellowing of broccoli during storage. The hydrogen peroxide
      content increased immediately after EAWP treatment but then remained at a low
      level during storage. Catalase (CAT) activity increased rapidly with EAWP
      treatment and was higher than that in the control for the first 4days of storage.
      The BoCAT gene expression level with EAWP treatment also showed a high trend as
      compared to the control. The gene expressions of BoRboh, BoCu/ZnSOD, and BoAPX
      showed almost the same tendency with or without EAWP treatment. These findings
      suggested that hydrogen peroxide formed by EAWP treatment and regulated by CAT
      could be relevant to maintaining the quality of broccoli.

PMID- 28764063
TI  - Hard cap espresso extraction and liquid chromatography determination of bioactive
      compounds in vegetables and spices.
AB  - A new analytical procedure, based on liquid chromatography with diode array and
      fluorescence detection, has been proposed for the determination of bioactive
      compounds in vegetables and spices after hard cap espresso extraction. This novel
      extraction system has been tested for the determination of capsaicin and
      dihydrocapsaicin from fresh chilli and sweet pepper, piperine from ground pepper,
      curcumin from turmeric and curry, and myristicin from nutmeg. Extraction
      efficiency was evaluated by using acetonitrile:water and ethanol:water mixtures.
      The proposed method allows the extraction of samples with 100mL of 60% (v/v)
      ethanol in water. The obtained limits of quantification for the proposed
      procedure ranged from 0.07 to 0.30mgg-1 and results were statistically comparable
      with those obtained by ultrasound assisted extraction. Hard cap espresso machines
      offer a fast, effective and quantitative tool for the extraction of bioactive
      compounds from food samples with an extraction time lower than 30s, using a
      global available and low cost equipment.

PMID- 28764064
TI  - Application of enzyme preparations for extraction of berry skin phenolics in
      withered winegrapes.
AB  - Postharvest withering of grapes strongly affects the content and extractability
      of phenolic compounds in the production of sfursat, fortified and passito wines.
      This work evaluated the effectiveness of enzymes applied individually and/or in
      multi-enzyme blends, on the extraction of anthocyanins, oligomeric flavanols and
      polymeric flavanols from withered grape skins during simulated maceration. The
      study was performed on Vitis vinifera L. cv. Nebbiolo and Barbera because of
      their different skin phenolic profile and cell wall composition. Our findings
      highlight that the relationship between skin mechanical properties (berry skin
      break force and energy) and extraction yield of phenolic compounds is variety
      dependent. Significant correlations were found between the skin softening
      associated with cell wall degradation and the extraction of anthocyanins and
      flavanols in Nebbiolo, for which polygalacturonase, individually or in multi
      enzyme blends, plays an important role. In Barbera, the extractability of
      phenolic compounds was not affected by the presence of exogenous enzymes.

PMID- 28764065
TI  - The use of two-dimensional NMR relaxometry in bread staling: a valuable tool?
AB  - Staling of bread was investigated in terms of physico-chemical parameters and one
      (1D) and two dimensional (2D) 1H Nuclear Magnetic Resonance (NMR) relaxometry.
      Physico-chemical properties were consistent with those generally reported for
      bread staling (crumb moisture loss, decrease in frozen water content, formation
      of amylopectin crystals, crumb hardening). One dimensional 1H NMR investigation
      suggested the presence of only one T1 protons population, while T2 was
      representative of multiple proton populations, that well related to the observed
      physico-chemical changes. 1H Two dimensional NMR provided an interesting insight
      of 1H T1 dynamics, as it allowed to discriminate the contribution of five protons
      pools within the 1H T1 relaxation.

PMID- 28764066
TI  - Novel multiplex qualitative detection using universal primer-multiplex-PCR
      combined with pyrosequencing.
AB  - This study described a novel multiplex qualitative detection method using
      pyrosequencing. Based on the principle of the universal primer-multiplex-PCR,
      only one sequencing primer was employed to realize the detection of the multiple
      targets. Samples containing three genetically modified (GM) crops in different
      proportions were used to validate the method. The dNTP dispensing order was
      designed based on the product sequences. Only 12 rounds (ATCTGATCGACT) of dNTPs
      addition and, often, as few as three rounds (CAT) under ideal conditions, were
      required to detect the GM events qualitatively, and sensitivity was as low as 1%
      of a mixture. However, when considering a mixture, calculating signal values
      allowed the proportion of each GM to be estimated. Based on these results, we
      concluded that our novel method not only realized detection but also allowed semi
      quantitative detection of individual events.

PMID- 28764067
TI  - Effect of Flavourzyme on proteolysis, antioxidant activity and sensory qualities
      of Cantonese bacon.
AB  - The aim of this study was to investigate the influence of Flavourzyme on protein
      degradation, antioxidant activity and sensory qualities of Cantonese bacon made
      at 60 degrees C for 28h. Flavourzyme was used at doses of 8, 16, 24, 32 and
      40LAUP/kg of raw meat. Results indicated that Flavourzyme addition in Cantonese
      bacon promoted proteolysis, which was reflected by the increase of various free
      amino acids and SDS-PAGE-detected changes in the myogen and myofibrillar
      proteins. Sensory qualities were improved while TPA (texture profile analysis)
      was decreased significantly (P<0.05). The best sensory scores were obtained at
      between 24 and 32LAPU/kg. Besides, Flavourzyme addition improved antioxidant
      activity, and decreased water activity and protein carbonyl content of Cantonese
      bacon. This study indicated that the addition of Flavourzyme improved eating
      attributes and storage stability of Cantonese bacon.

PMID- 28764068
TI  - The transfer of natural Rhodamine B contamination from raw paprika fruit to
      capsicum oleoresin during the extraction process.
AB  - Occurrence of Rhodamine B (RhB) contamination in paprika caused by agricultural
      materials during the vegetation process has been reported. It may transfer during
      the process of active compounds extraction, and eventually exist in final
      products. Herein, the re-distribution of RhB during the extraction process was
      assessed in terms of RhB contents, as well as mass, color value and capsaicinoids
      yield of each process. Results revealed that natural RhB contamination at 0.55
      1.11ug/kg originated from raw paprika fruit then transferred with the extraction
      proceeded. About 95.5% of RhB was found in red oleoresin. After separation of red
      oleoresin, 91.6% of RhB was remained in capsicum oleoresin, only 3.7% in paprika
      red. These results were consistent with total capsaicinoids recovery of each
      product. The RhB levels in edible capsicum oleoresin in our present study at 0.01
      0.34ug/kg did not exceed the legal limits established by the European Union.

PMID- 28764069
TI  - Effects of pulsed electric field on intracellular antioxidant activity and
      antioxidant enzyme regulating capacities of pine nut (Pinus koraiensis) peptide
      QDHCH in HepG2 cells.
AB  - Effects of pulse electric field (PEF) on antioxidant activity of pine nut (Pinus
      koraiensis) peptide were discussed using H2O2-induced HepG2 cells and changes of
      peptide structures were measured by MIR, NMR and CD spectra. Using HPLC-MS/MS, a
      novel peptide was identified as QDHCH. After PEF treatment the DPPH and ABTS
      radical inhibition, and CAA values of QDHCH were increased to 85.13%+/-0.17%,
      95.45%+/-0.12%, and 4670.10MUmol of quercetin equivalents/100g. The PEF-treated
      QDHCH has better protective oxidative stress inhibitory of 74.22+/-3.70%, and the
      T-SOD, CAT, GSH-Px and GSH-Rx activities in cells were significantly increased by
      91.92, 7.98, 18.5 and 18.79U/mg prot, while the MDA content was decreased to
      8.45+/-0.71U/mg prot compared with H2O2 damaged group. In addition, the hydroxyl
      radical scavenging activity of QDHCH was increased by 10.53%; the basic structure
      was not changed by PEF, while the influenced secondary structures may induce the
      antioxidant activity improvement in HepG2 cells.

PMID- 28764070
TI  - Folate-targeted nanostructured lipid carriers for enhanced oral delivery of
      epigallocatechin-3-gallate.
AB  - The well-known pleiotropic health benefits of green tea are mainly attributed to
      epigallocatechin-3-gallate (EGCG), a polyphenolic compound from the group of
      catechins. EGCG's poor stability and intestinal permeability, however, can
      strongly impair its biological activities. In this work, EGCG-loaded
      nanostructured lipid carriers (NLC) functionalized with folic acid were optimized
      through a Box-Behnken design intended to provide an enhanced oral absorption and
      increased bioavailability of EGCG. Size, zeta potential and encapsulation
      efficiency (EE) of the produced spherical nanoparticles were evaluated. NLC were
      further characterized by Differential Scanning Calorimetry (DSC). An in vitro
      release study in simulated gastric and intestinal fluids was conducted and the
      storage stability of the nanoparticles was evaluated over a period of 8weeks. The
      overall results demonstrated the suitability of the developed formulation for the
      oral delivery of EGCG and its potential for applications in food industry.

PMID- 28764071
TI  - Determination of total iron-reactive phenolics, anthocyanins and tannins in wine
      grapes of skins and seeds based on near-infrared hyperspectral imaging.
AB  - Phenolics contents in wine grapes are key indicators for assessing ripeness. Near
      infrared hyperspectral images during ripening have been explored to achieve an
      effective method for predicting phenolics contents. Principal component
      regression (PCR), partial least squares regression (PLSR) and support vector
      regression (SVR) models were built, respectively. The results show that SVR
      behaves globally better than PLSR and PCR, except in predicting tannins content
      of seeds. For the best prediction results, the squared correlation coefficient
      and root mean square error reached 0.8960 and 0.1069g/L (+)-catechin equivalents
      (CE), respectively, for tannins in skins, 0.9065 and 0.1776 (g/L CE) for total
      iron-reactive phenolics (TIRP) in skins, 0.8789 and 0.1442 (g/L M3G) for
      anthocyanins in skins, 0.9243 and 0.2401 (g/L CE) for tannins in seeds, and
      0.8790 and 0.5190 (g/L CE) for TIRP in seeds. Our results indicated that NIR
      hyperspectral imaging has good prospects for evaluation of phenolics in wine
      grapes.

PMID- 28764072
TI  - Chitosan as a novel clarifying agent on clear apple juice production:
      Optimization of process conditions and changes on quality characteristics.
AB  - In this study, the use of chitosan as a clarification agent in the production of
      clear apple juice (AJ) was investigated, the optimum conditions were determined
      using RSM, and the effects on the quality of AJ were analyzed during storage at 4
      degrees C and 20 degrees C for 4months. Optimum conditions for clarifying the AJ
      were chitosan concentration of 191.6mg/100ml juice, the process temperature of 20
      degrees C and process time of 30min. Changes in quality characteristics such as
      turbidity, pH, acidity, color, total monomeric anthocyanin, total phenolic, and
      protein contents were evaluated and compared to traditional clarification.
      Alicyclobacillus acidoterrestris causes significant safety issues in fruit juice
      industry; therefore also the antimicrobial effect of chitosan on A.
      acidoterrestris during the clarification process was examined. The results showed
      that clear AJ production can be achieved by the clarification step with direct
      chitosan addition, without the need for enzymatic treatment. However, the
      microbial reduction of A. acidoterrestris during the clarification process was
      not found to be significant.

PMID- 28764073
TI  - An improved process for the production of highly purified recombinant thaumatin
      tagged-variants.
AB  - The sweetest tasting molecule known is the protein thaumatin, first isolated from
      the katemfe fruit, Thaumatococcus daniellii. Thaumatin is used in the food and
      beverage industry as a low-calorie sugar substitute. Thaumatin interacts with
      taste receptors in the oral cavity eliciting a persistent sweet taste and a
      bitter, liquorice flavor. Recombinant thaumatin was expressed in Pichia pastoris
      and through a co-expression strategy with a molecular chaperone, yields of one
      engineered thaumatin variant increased by greater than two-fold. A detailed
      purification strategy for thaumatin is reported resulting in a homogenous sample
      recovered at a yield of 42%. The recombinant thaumatins were extensively
      characterised using size exclusion chromatography for homogeneity, reversed-phase
      HPLC for purity (99%), peptide digest LC-MS/MS for sequence determination, and
      circular dichroism and tryptophan fluorescence spectroscopies for conformational
      characterisation. These new thaumatin variants are amenable for bioconjugation,
      providing chemical biology tools for thaumatin:taste receptor interaction
      studies.

PMID- 28764074
TI  - Successive harvesting affects yield, chemical composition and antioxidant
      activity of Cichorium spinosum L.
AB  - In the present study, the effect of successive harvesting on yield, chemical
      composition and antioxidant activity of Cichorium spinosum plants was examined.
      C. spinosum plants were grown from seeds sown in seed trays containing peat and
      young seedlings were transplanted in 2L pots containing peat and perlite
      (1:1v/v). Plants were harvested two or three times during two consecutive growing
      periods. Total fresh weight and number of leaves were higher for successive
      harvests in both growing periods comparing to a single harvest. The application
      of more than two harvests resulted in quality loss during the 1st growing period,
      while in the 2nd growing period the overall chemical composition, antioxidant
      properties and phenolic compounds content was higher than the 1st period. In
      conclusion, cultivation practices such as sowing date and successive harvesting
      may be useful tools towards the production of high quality end-product with
      increased bioactive properties without compromising total yield.

PMID- 28764075
TI  - Size-exclusion chromatography (HPLC-SEC) technique optimization by simplex method
      to estimate molecular weight distribution of agave fructans.
AB  - Agave fructans are increasingly important in food industry and nutrition sciences
      as a potential ingredient of functional food, thus practical analysis tools to
      characterize them are needed. In view of the importance of the molecular weight
      on the functional properties of agave fructans, this study has the purpose to
      optimize a method to determine their molecular weight distribution by HPLC-SEC
      for industrial application. The optimization was carried out using a simplex
      method. The optimum conditions obtained were at column temperature of 61.7
      degrees C using tri-distilled water without salt, adjusted pH of 5.4 and a flow
      rate of 0.36mL/min. The exclusion range is from 1 to 49 of polymerization degree
      (180-7966Da). This proposed method represents an accurate and fast alternative to
      standard methods involving multiple-detection or hydrolysis of fructans. The
      industrial applications of this technique might be for quality control, study of
      fractionation processes and determination of purity.

PMID- 28764076
TI  - A sensitive HPLC-MS/MS method for the simultaneous detection of microbial
      transglutaminase, and bovine and porcine fibrinogen/thrombin in restructured
      meat.
AB  - A sensitive HPLC-MS/MS method for the simultaneous detection of microbial
      transglutaminase (TG) from Streptomyces mobaraensis, and bovine and porcine
      fibrinogen/thrombin in restructured meat was developed using tryptic marker
      peptides of TG (five markers), and bovine and porcine fibrinogen (six markers
      each). Meat binding experiments with beef and pork were performed using a
      technical TG mixture (Activa, Ajinomoto), and bovine and porcine plasmapowder FG
      (PPFG; Sonac B.V.). The method developed allows the simultaneous detection of the
      use of these cold-set binders in raw and heated samples. The peak areas of the
      fibrinogen marker peptides were increased by a factor of about 100, compared to
      blank values originating from the occurrence of residual blood in meat, using a
      concentration of 0.6% bovine and porcine PPFG. A differentiation between the use
      of blood plasma powder and PPFG using the ratios of fibrinogen to serotransferrin
      peptide peak areas seems to be possible.

PMID- 28764077
TI  - Levels of lead in foods from the first French total diet study on infants and
      toddlers.
AB  - Infants and toddlers are highly vulnerable to exposure to lead due to its higher
      absorption in small children than in adults. This study describes the
      optimisation and validation of a very sensitive method for the determination of
      low levels of lead in foods mostly consumed by infants and toddlers. This method,
      based on inductively coupled plasma-mass spectrometry with a programmable
      temperature cyclonic spray chamber, attained a limit of quantification (LOQ) of
      0.6 or 0.9ugPbkg-1 for a liquid or a solid sample, that was improved by a factor
      5.6-8.3 compared to the previous method (LOQ: 5ugkg-1). The analytical method was
      then applied to 291 food samples from the first French total diet study on
      infants and toddlers. Lead was detected in most samples at relatively low
      concentrations (range 0.0-16ugkg-1). The highest lead concentrations were mainly
      found in processed food products (e.g. products containing chocolate).

PMID- 28764078
TI  - Application of chemometrics in quality control of Turmeric (Curcuma longa) based
      on Ultra-violet, Fourier transform-infrared and 1H NMR spectroscopy.
AB  - Turmeric (Curcuma longa L.) belongs to the family Zingiberaceae that is widely
      used as a spice in food preparations in addition to its biological activities.
      UV, FT-IR, 1H NMR in addition to HPLC were applied to construct a metabolic
      fingerprint for Turmeric in an attempt to assess its quality. 30 samples were
      analyzed, and then principal component analysis (PCA) and hierarchical clustering
      analysis (HCA) were utilized to assess the differences and similarities between
      collected samples. PCA score plot based on both HPLC and UV spectroscopy showed
      the same discriminatory pattern, where the samples were segregated into four main
      groups depending on their total curcuminoids content. The results revealed that
      UV could be utilized as a simple and rapid alternative for HPLC. However, FT-IR
      failed to discriminate between the same species. By applying 1H NMR, the
      metabolic variability between samples was more evident in the essential
      oils/fatty acid region.

PMID- 28764079
TI  - Seasonal variation of polar lipid content in bovine milk.
AB  - Seasonal change of milk composition could offer opportunities for dairy
      manufacturers. A systematic survey on seasonal variation of six classes of polar
      lipids was conducted with 19 Holstein cows over the entire milking season using
      liquid chromatography-mass spectrometry technique. This study revealed that most
      polar lipid classes were positively correlated with the total fat content, but
      negatively correlated with fat globule size. All polar lipid classes displayed a
      large cow-to-cow variation as well as seasonal variation. All of the six classes
      showed a gradual increase over the milking season with the highest concentration
      observed in May (autumn). However, the proportion of different polar lipid
      classes remained constant during the entire milking season. This finding suggests
      that the production of polar lipids is highly regulated in the mammary gland. The
      implication of such a seasonal variation of polar lipids in the nutritional and
      technological aspects of milk is discussed.

PMID- 28764080
TI  - Supramolecular solvents combined with layered double hydroxide-coated magnetic
      nanoparticles for extraction of bisphenols and 4-tert-octylphenol from fruit
      juices.
AB  - A magnesium-aluminum layered double hydroxides coated on magnetic nanoparticles
      (Fe3O4@MgAl-LDHs NPs) combined with the supramolecular solvents (SUPRASs) as the
      magnetic supramolecular fluids were successfully applied to the extraction and
      determination of four phenolic compounds (Bisphenol-A (BPA), bisphenol-AF (BPAF),
      tetrabromobisphenol-A (TBBPA) and 4-tert-octylphenol (4-TOP)). Magnetic
      supramolecular fluids (ferrofluids) composites were prepared through adding the
      mixture of n-octanol and tetrahydrofuran in distilled water as the supramolecular
      solvents into the solution containing magnetic Fe3O4@MgAl-LDHs NPs. Under the
      optimized conditions, the calibration curve was obtained in range of 5-1000MUgL
      1. The limits of detection (S/N=3) for BPA, BPAF, TBBPA and 4-TOP, were obtained
      for 0.54, 0.48, 0.37 and 0.63MUgL-1, respectively. The intra-day and inter-day
      precision (RSDs %) for bisphenols (BPs) and 4-TOP at 100 and 300MUgL-1 were in
      the range of 4.0-7.8. The enrichment factors were between 16 and 24.

PMID- 28764081
TI  - First identification and quantification of S-3-(hexan-1-ol)-gamma-glutamyl
      cysteine in grape must as a potential thiol precursor, using UPLC-MS/MS analysis
      and stable isotope dilution assay.
AB  - Varietal thiols are key aroma compounds in wine issued from multiple and complex
      origins. Several precursor families have been identified in grapes and must and
      have been widely studied. But a large part of thiol origin still remains unknown.
      Thus, we only have an incomplete picture of thiol precursors and there is a lack
      of knowledge on pre-fermentative mechanisms that can impact their levels. Our
      study focused on the formal identification and the quantification of new varietal
      thiol precursors in must. First of all, we synthesized natural and labeled
      standards using an original multi-step strategy, then we developed and validated
      a UPLC-MS/MS method that allowed us to identify and quantify for the first time a
      dipeptide S-conjugate to 3MH, the gammaGluCys-3MH, in Sauvignon B. We observed
      the S-4-mercapto-4-methylpentan-2-one-l-cysteinyl-glycine (CysGly-4MMP) and S-4
      mercapto-4-methylpentan-2-one-N-(l-gamma-glutamyl)-l-cysteine (gammaGluCys-4MMP)
      but at too low concentration to be quantified.

PMID- 28764082
TI  - Biotransformation and metabolism of three mulberry anthocyanin monomers by rat
      gut microflora.
AB  - Anthocyanins (ACNs) are naturally occurring components of human diet. Evidence
      has accumulated regarding the positive association of their intake with chronic
      disease. Because microbiota has been considered as a metabolic organ, the
      bacterial-dependent metabolisms of three types of ACNs from mulberry fruits
      (cyanidin-3-glucoside (C3G), cyanidin-3-rutinoside (C3R), delphinidin-3
      rutinoside (D3R)) during a simulation of large intestine conditions were
      investigated. ACNs and metabolites were analysed and characterized by high
      performance liquid chromatography-electrospray ionization-mass spectrum (HPLC-ESI
      MS/MS). C3G disappeared after 6h of metabolism, while C3R and D3R were no longer
      detected after 8h. The metabolism of C3G and C3R mainly resulted in the formation
      of protocatechuic, vanillic, and p-coumaric acids, as well as 2,4,6
      trihydroxybenzaldehyde, while the main metabolites of D3R were gallic acid,
      syringic acid and 2,4,6-trihydroxybenzaldehyde. This research indicated that the
      intake of ACNs may result in the appearance of specific metabolites that exert a
      protective effect in the host physiology.

PMID- 28764083
TI  - In silico and in vitro inhibition of cytochrome P450 3A by synthetic stilbenoids.
AB  - Inhibition of cytochrome P450 3A4 (CYP3A4), the major drug metabolizing enzyme,
      by dietary compounds has recently attracted increased attention. Evaluating the
      potency of the many known inhibitory compounds is a tedious and time consuming
      task, yet it can be achieved using computing tools. Here, CDOCKER and Glide
      served to design model inhibitors in order to characterize molecular features of
      an inhibitor. Assessing nitro-stilbenoids, both approaches suggested
      nitrostilbene to be a weaker inhibitor of CYP3A4 than resveratrol, and stronger
      than dimethoxy-nitrostilbene. Nitrostilbene and resveratrol, but not dimethoxy
      nitrostilbene, engage electrostatic interactions in the enzyme cavity, and with
      the haem. In vitro assessment of the inhibitory capacity supported the in silico
      predictions, suggesting that evaluating the electrostatic interactions of a
      compound with the prosthetic group allows the prediction of inhibitory potency.
      Since both programs yielded related results, it is suggested that for CYP3A4,
      computing tools may allow rapid identification of potent dietary inhibitors.

PMID- 28764084
TI  - Determination of antimony and tin in beverages using inductively coupled plasma
      optical emission spectrometry after ultrasound-assisted ionic liquid dispersive
      liquid-liquid phase microextraction.
AB  - The aim of this study was to develop a simple and fast ultrasound-assisted ionic
      liquid dispersive liquid-liquid phase microextraction (UA-IL-DLLME) method for
      preconcetration of trace antimony and tin in beverage samples. The novelty of
      this study was based on the application of ligandless UA-IL-DLLME using low
      density ionic liquid and organic solvents for preconcentration of Sb and Sn. The
      concentration of Sb and Sn were quantified using ICP-OES. Under the optimum
      conditions, the calibration graph was found to be LOQ-250ugL-1 (r2=0.9987) for Sb
      and LOQ-350ugL-1 for Sn. The LOD and LOQ of Sb and Sn ranged from 1.2to 2.5ngL-1
      and 4.0 to 8.3ngL-1, respectively, with high preconcentration factors. The
      precisions (%RSD) of the proposed method ranged from 2.1% to 2.5% and 3.9% to
      4.7% for Sb and Sn, respectively. The proposed method was successfully applied
      for determination of Sb and Sn in beverages.

PMID- 28764085
TI  - Effect of light irradiation on the antioxidant stability of oleuropein.
AB  - The stability of oleuropein, a natural antioxidant from Olea europaea, has been
      often studied in connection with thermal or enzymatic treatments, but very little
      is known about the effects of UV light. This work aimed at studying the UV-C
      effects on oleuropein standard solutions once dissolved in ethanol or water.
      During irradiation, aliquots were taken and analyzed by a flow injection system
      equipped with a multi-channel coulometric detector and a high-resolution mass
      spectrometer. The effects of irradiation were also studied by UV spectroscopy.
      The results show that oleuropein is relatively stable in water or ethanol, but
      that under UV-C light undergoes a series of fast decomposition reactions leading
      to hydroxytyrosol and elenolic acid. Overall, this study provides evidences that
      the degradation of oleuropein by UV-C light follows a mechanism dependent on the
      solvent used. Moreover, the solvent affects the resulting redox properties of the
      solution.

PMID- 28764086
TI  - Graphite nanocomposites sensor for multiplex detection of antioxidants in food.
AB  - Butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and tert
      butylhydroquinone (TBHQ) are synthetic antioxidants used in the food industry.
      Herein, we describe the development of a novel graphite nanocomposite-based
      electrochemical sensor for the multiplex detection and measurement of BHA, BHT,
      and TBHQ levels in complex food samples using a linear sweep voltammetry
      technique. Moreover, our newly established analytical method exhibited good
      sensitivity, limit of detection, limit of quantitation, and selectivity. The
      accuracy and reliability of analytical results were challenged by method
      validation and comparison with the results of the liquid chromatography method,
      where a linear correlation of more than 0.99 was achieved. The addition of sodium
      dodecyl sulfate as supporting additive further enhanced the LSV response (anodic
      peak current, Ipa) of BHA and BHT by 2- and 20-times, respectively.

PMID- 28764087
TI  - Synthesis, characterization, and application of a Zn (II)-imprinted polymer
      grafted on graphene oxide/magnetic chitosan nanocomposite for selective
      extraction of zinc ions from different food samples.
AB  - A novel Zn(II) imprinted polymer was synthesized via a co-precipitation method
      using graphene oxide/magnetic chitosan nanocomposite as supporting material. The
      synthesized imprinted polymer was characterized by Fourier transform infrared
      spectrometry (FTIR) and scanning electron microscopy (SEM) and applied as a
      sorbent for selective magnetic solid phase extraction of zinc followed by its
      determination by flame atomic absorption spectrometry. The kinetic and isothermal
      adsorption experiments were carried out and all parameters affecting the
      extraction process was optimized. Under the optimal experimental conditions, the
      developed procedure exhibits a linear dynamic range of 0.5-5.0ugL-1 with a
      detection limit of 0.09ugL-1 and quantification limit of 0.3ugL-1. The maximum
      sorption capacity of the sorbent was found to be 71.4mgg-1. The developed
      procedure was successfully applied to the selective extraction and determination
      of zinc in various samples including well water, drinking water, black tea, rice,
      and milk.

PMID- 28764088
TI  - A novel flow injection chemiluminescence method for automated and miniaturized
      determination of phenols in smoked food samples.
AB  - An easily performed fully automated and miniaturized flow injection
      chemiluminescence (CL) method for determination of phenols in smoked food samples
      has been proposed. This method includes the ultrasound assisted solid-liquid
      extraction coupled with gas-diffusion separation of phenols from smoked food
      sample and analytes absorption into a NaOH solution in a specially designed gas
      diffusion cell. The flow system was designed to focus on automation and
      miniaturization with minimal sample and reagent consumption by inexpensive
      instrumentation. The luminol - N-bromosuccinimide system in an alkaline medium
      was used for the CL determination of phenols. The limit of detection of the
      proposed procedure was 3.10-8.molL-1 (0.01mgkg-1) in terms of phenol. The
      presented method demonstrated to be a good tool for easy, rapid and cost
      effective point-of-need screening phenols in smoked food samples.

PMID- 28764089
TI  - The effects of chilling stress after anthesis on the physicochemical properties
      of rice (Oryza sativa L) starch.
AB  - This study investigates the effect of chilling stress, over a period of three
      days after anthesis, on the physicochemical properties of starches derived from
      six rice cultivars. Chilling stress significantly affected the grain
      characteristics and physicochemical properties of rice starches, except for those
      of two varieties, NJ 9108 and ZD 18. In the other four rice cultivars subjected
      to chilling stress, the content of medium, and large sized granules showed a
      decrease, and an increase, respectively. Amylose content increased as a result of
      chilling stress, thereby resulting in starch with a lower swelling power, water
      solubility, and higher retrogradation enthalpy and gelatinization temperature.
      Chilling stress led to deterioration of cooked rice quality as determined by the
      pasting properties of starch. This study indicated that among the cultivars
      studied, the two rice varieties most resistant to chilling stress after rice
      anthesis were NJ 9108 and ZD 18.

PMID- 28764090
TI  - Synthesis, characterization and application of a new fluorescence reagent for the
      determination of aluminum in food samples.
AB  - A new sensitive fluorimetry method for the simple and rapid measurement of
      aluminum in some food samples, which used 3',6'-bis(diethylamino)-2-{[(1E)-(4
      ethoxyphenyl) methylene] amino}spiro[isoindole-1,9'-xanthen]-3(2H)-one (DEMAX)
      for Al(III) chelation is described herein. The fluorescence intensity of the
      aluminum-DEMAX complex remains unaltered for over 24h at room temperature and is
      a linear function of the concentration of aluminum in the 0-1000mg/L range with a
      detection limit (LOD, defined as 3s/b) of 3.02ugL-1 and quantification limit
      (LOQ, defined as 10Sb/m) of 30ugL-1. The relative standard deviation (RSD) was
      0.1% for a 1ugL-1 aluminum level. The influences of the analytical parameters
      such as pH, waiting time of aluminum-DEMAX complex, amount of reagent, effect of
      temperature etc. were investigated. The developed method was successfully used
      for assaying aluminum in some food samples and dialysis solution, measured by the
      new home-made fluorimetric system. The results of analysis of the certified
      reference material (INCT-TL-1) are in good agreement with the certified value.

PMID- 28764091
TI  - Development of functional yogurt containing free and encapsulated echium oil,
      phytosterol and sinapic acid.
AB  - The consumption of omega-3 fatty acids and phytosterol promotes the reduction of
      cholesterol and triacylglycerol levels. However, such compounds are susceptible
      to oxidation, which hampers their application. The objective of this work was to
      coencapsulate echium oil, phytosterols and sinapic acid
      (crosslinker/antioxidant), and incorporate the obtained microcapsules into
      yogurt. The microcapsules were evaluated for particle size, accelerated oxidation
      by Rancimat, and simulation of gastric/intestinal release. The yogurts were
      assessed for morphology, pH, titratable acidity, color, rheology and sensory
      analysis. The microcapsules (13-42MUm) promoted protection against oil oxidation
      (induction time of 54.96h). The yogurt containing microcapsules, presented a pH
      range from 3.89 to 4.17 and titratable acidity range from 0.798 to 0.826%, with
      good sensorial acceptance. It was possible to apply the microcapsules in yogurt,
      without compromising the rheological properties and physicochemical stability of
      the product.

PMID- 28764092
TI  - Starch digestibility and predicted glycemic index in the bread fortified with
      pomelo (Citrus maxima) fruit segments.
AB  - The aim of this study was to evaluate the starch digestibility and predicted
      glycemic index in breads incorporated with pomelo fruit (Citrus maxima) segments.
      Volume of the white and brown breads supplemented with pomelo fresh segments
      increased, while the crumb firmness decreased. Bread with 20% fresh and 5% dry
      pomelo segments were sensorily acceptable. Bioactive components such as
      phenolics, flavonoids, naringin and carotenoids were retained to a greater extent
      in bread containing dry pomelo segments. The pomelo incorporated bread had higher
      levels of resistant starch fractions (3.87-10.96%) with low predicted glycemic
      index (62.97-53.13%), despite their higher total starch (69.87-75.47%) content
      compared to control bread. Thus pomelo segments in the product formulations
      lowered the glycemic index probably by inhibiting carbohydrate hydrolyzing enzyme
      activity which could be attributed to naringin. Hence fortified bread prepared
      from pomelo fruit segment is recommended to gain nutritional value and to
      decrease the risk of diabetes.

PMID- 28764093
TI  - Acriflavine-immobilized eggshell membrane as a new solid-state biosensor for
      Sudan I-IV detection based on fluorescence resonance energy transfer.
AB  - A novel solid-surface fluorescence biosensor for rapid detection of Sudan I-IV
      was proposed based on fluorescence resonance energy transfer (FRET). The
      biosensor was fabricated by immobilizing acriflavine (AY) on the eggshell
      membrane (ESM) with glutaraldehyde as cross-linking agent. FRET mechanism was
      demonstrated by using AY and Sudan dyes as donor and acceptor respectively, an
      efficient energy transfer in the present system was indicated by the sufficient
      spectral overlap integral (J) and proper Forster critical distance (R0). Under
      optimum conditions, the fluorescence of the AY-ESM could be efficiently quenched
      by Sudan I-IV and the corresponding linear range was 0.5-60MUM with the detection
      limits (3sigma/slope) of 0.16, 0.26, 0.21 and 0.17MUM respectively. Compared to
      the detection of Sudan dyes in solution-state, the membrane biosensor exhibited
      advantages of low detection limits, high sensitivity and selectivity, as well as
      excellent stability. Recovery tests in spiked real samples also achieved
      satisfactory results.

PMID- 28764094
TI  - Design of a silver nanoparticle for sensitive surface enhanced Raman spectroscopy
      detection of carmine dye.
AB  - Flower-shaped silver nanoparticles have been successfully synthesized by a simple
      aqueous phase silver nitrate reduction by ascorbic acid in the presence of
      polyvinylpyrrolidone (PVP) surfactant. The nanoparticles diameters were adjusted
      from 450 to 1000nm with surface protrusions up to 10-25nm. The growth direction
      of silver nuclei is controlled by their degree of coating by PVP. The flower
      shaped silver nanostructures obtained were used as stable Surface Enhanced Raman
      Scattering (SERS) substrates with high SERS activity for detecting Rhodamine 6G
      (R6G), at a concentration of only 10-9M, where the SERS signal is still clear.
      SERS spectra of the dye carmine was analysed and the characteristic bands were
      identified. An improved principle component analysis (PCA) was used for carmine
      detection, at concentrations down to 10-8M. The characteristic peaks of the
      carmine (1019, 1360, and 1573cm-1) remained at 10-8M. This indicated that the
      minimum detection limit of AgNP-based substrate for carmine is about 10-8M.

PMID- 28764095
TI  - Effects of frying oils' fatty acids profile on the formation of polar lipids
      components and their retention in French fries over deep-frying process.
AB  - The effects of frying oils' fatty acids profile on the formation of polar
      components and their retention in French fries and corresponding deep-fried oils
      were investigated in the present study, using oils with different fatty acids
      composition. Our analysis showed that the total polar compounds (TPCs) content in
      French fries was only slightly lower than that in deep-fried oils, indicating
      that there was no significant difference considering the amounts of TPCs in
      French fries and deep-fried oils. Our further analysis showed that different
      polar components in TPCs distributed differently in deep-fried oils and oils
      extracted from French fries. Specifically, the level of oligomeric and dimeric
      triacylglycerols was higher in French fries while oxidized triacylglycerols and
      diacylglycerols content was higher in deep-fried oils. The different retention of
      TPCs components in French fries may be explained by their interactions with
      carbohydrates, which are shown to enhance with the increase of hydrophobic
      property. Chemometric analysis showed that no correlation between the polar
      compounds level and saturated fatty acids profile was observed. Meanwhile, the
      polar compounds content was highly correlated with the formation of trans-C18:1,
      and a highly positive association between polar compounds and C18:2 content was
      also observed in palm oil.

PMID- 28764096
TI  - Changes in anthocyanidin levels during the maturation of color-fleshed potato
      (Solanum tuberosum L.) tubers.
AB  - Certain potato cultivars are capable of producing anthocyanin pigments in the
      potato skin and flesh and those pigments have been shown, together with other
      phytochemicals, to promote good health. Six common anthocyanidins (cyanidin,
      delphinidin, petunidin, pelargonidin, malvidin and peonidin) were analyzed weekly
      for 15weeks in red- and purple-fleshed potato cultivars (Red Emma, Konigspurpur,
      Valfi and Blaue de la Mancha) grown in field conditions using a validated LC
      (+ESI)MS/MS method. Pelargonidin was the major type detected in red-fleshed
      cultivars whereas petunidin was the major type detected in the purple ones.
      Neither cyanidin nor delphinidin were found in any of the cultivars. The
      anthocyanidin levels observed were as high as 78mg/100g FW during tuber growth;
      however, fully matured tubers contained only 10-39mg anthocyanidins/100gFW.
      Anthocyanidin levels were moderately correlated with global solar irradiation
      (r<0.6252) but not with rainfall or daily temperature.

PMID- 28764097
TI  - Interactions between macromolecule-bound antioxidants and Trolox during liposome
      autoxidation: A multivariate approach.
AB  - The interactions between free and macromolecule-bound antioxidants were
      investigated in order to evaluate their combined effects on the antioxidant
      environment. Dietary fiber (DF), protein and lipid-bound antioxidants, obtained
      from whole wheat, soybean and olive oil products, respectively and Trolox were
      used for this purpose. Experimental studies were carried out in autoxidizing
      liposome medium by monitoring the development of fluorescent products formed by
      lipid oxidation. Chemometric methods were used both at experimental design and
      multivariate data analysis stages. Comparison of the simple addition effects of
      Trolox and bound antioxidants with measured values on lipid oxidation revealed
      synergetic interactions for DF and refined olive oil-bound antioxidants, and
      antagonistic interactions for protein and extra virgin olive oil-bound
      antioxidants with Trolox. A generalized version of logistic function was
      successfully used for modelling the oxidation curve of liposomes. Principal
      component analysis revealed two separate phases of liposome autoxidation.

PMID- 28764098
TI  - Two acidic, thermophilic GH28 polygalacturonases from Talaromyces leycettanus JCM
      12802 with application potentials for grape juice clarification.
AB  - Efficient hydrolysis of pectic materials to sugars requires the synergistic
      action of endo- and exo-polygalacturonases. Two novel polygalacturonases (exo
      TePG28a and endo-TePG28b) were identified in Talaromyces leycettanus JCM12802,
      overexpressed in Pichia pastoris, and characterized in this report. The specific
      activities of TePG28a and TePG28b towards polygalacturonic acid were 280+/-9 and
      25,900+/-502U/mg, respectively. Both enzymes exhibited optimal activities at pH
      3.5 and retained highly stable over a broad pH range of 2.0-7.0. Distinct from
      most fungal polygalacturonases that have low temperature optima, TePG28a and
      TePG28b were optimally active at 70 degrees C. When treated the grape juice with
      the enzyme combination (the unit ratio of TePG28a:TePG28b was 1:4), higher pectin
      degrading efficiency (up to 140%) was achieved, and light transmittance was
      improved from 14% to 82%. These favorable enzymatic properties make TePG28a and
      TePG28b attractive for the applications in the juice industry.

PMID- 28764099
TI  - Degradation mechanisms of Microcystin-LR during UV-B photolysis and UV/H2O2
      processes: Byproducts and pathways.
AB  - The removal and degradation pathways of microcystin-LR (MC-LR, [M+H]+ = 995.6) in
      UV-B photolysis and UV-B/H2O2 processes were examined using liquid chromatography
      tandem mass spectrometry. The UV/H2O2 process was more efficient than UV-B
      photolysis for MC-LR removal. Eight by-products were newly identified in the UV-B
      photolysis ([M+H]+ = 414.3, 417.3, 709.6, 428.9, 608.6, 847.5, 807.4, and 823.6),
      and eleven by-products were identified in the UV-B/H2O2 process ([M+H]+ = 707.4,
      414.7, 429.3, 445.3, 608.6, 1052.0, 313.4, 823.6, 357.3, 245.2, and 805.7). Most
      of the MC-LR by-products had lower [M+H]+ values than the MC-LR itself during
      both processes, except for the [M+H]+ value of 1052.0 during UV-B photolysis.
      Based on identified by-products and peak area patterns, we proposed potential
      degradation pathways during the two processes. Bond cleavage and intramolecular
      electron rearrangement by electron pair in the nitrogen atom were the major
      reactions during UV-B photolysis and UV-B/H2O2 processes, and hydroxylation by OH
      radical and the adduct formation reaction between the produced by-products were
      identified as additional pathways during the UV-B/H2O2 process. Meanwhile, the
      degradation by-products identified from MC-LR during UV-B/H2O2 process can be
      further degraded by increasing H2O2 dose.

PMID- 28764100
TI  - Identifying sources of metal exposure in organic and conventional dairy farming.
AB  - In humans the main route of exposure to toxic metals is through the diet, and
      there is therefore a clear need for this source of contamination to be minimized,
      particularly in food of animal origin. For this purpose, the various sources of
      toxic metals in livestock farming (which vary depending on the production system)
      must be taken into account. The objectives of the present study were to establish
      the profile of metal exposure in dairy cattle in Spain and to determine, by
      chemometric (multivariate statistical) analysis, any differences between organic
      and conventional systems. Blood samples from 522 cows (341 from organic farms and
      181 from conventional farms) were analysed by inductively coupled plasma mass
      spectrometry to determine the concentrations of 14 elements: As, Cd, Co, Cr, Cu,
      Fe, Hg, I, Mn, Mo, Ni, Pb, Se and Zn. In conventional systems the generally high
      and balanced trace element concentrations in the mineral-supplemented concentrate
      feed strongly determined the metal status of the cattle. However, in organic
      systems, soil ingestion was an important contributing factor. Our results
      demonstrate that general information about the effects of mineral supplementation
      in conventional farming cannot be directly extrapolated to organic farming and
      special attention should be given to the contribution of ingestion of soil during
      grazing and/or ingestion of soil contaminated forage.

PMID- 28764101
TI  - Probing the binding properties of dicyandiamide with pepsin by spectroscopy and
      docking methods.
AB  - Dicyandiamide (DCD), considered to be a nitrification inhibitor, poses threat to
      human's health with exposure from milk, infant formula and other food products.
      In this work, DCD was investigated for its binding reaction with pepsin using
      spectroscopy and docking methods. Fluorescence experiments indicated DCD quenched
      the fluorescence of pepsin through a static process. Thermodynamic analysis of
      the binding data (DeltaH0 = -21.72 kJ mol-1 and DeltaS0 = 17.61 J mol-1 K-1)
      suggested the involvement of hydrophobic and hydrogen bonding in the complex
      formation. The pepsin interacted with DCD at a hydrophobic cavity, leading to a
      conformational changes in the pepsin, as revealed from UV-vis absorption, Fourier
      transform infrared, the time-resolved fluorescence, three-dimensional
      fluorescence and circular dichroism spectral results.

PMID- 28764102
TI  - Assessment of metal ion concentration in water with structured feature selection.
AB  - We propose a cost-effective system for the determination of metal ion
      concentration in water, addressing a central issue in water resources management.
      The system combines novel luminometric label array technology with a machine
      learning algorithm that selects a minimal number of array reagents (modulators)
      and liquid sample dilutions, such that enable accurate quantification. The
      algorithm is able to identify the optimal modulators and sample dilutions leading
      to cost reductions since less manual labour and resources are needed. Inferring
      the ion detector involves a unique type of a structured feature selection
      problem, which we formalize in this paper. We propose a novel Cartesian greedy
      forward feature selection algorithm for solving the problem. The novel algorithm
      was evaluated in the concentration assessment of five metal ions and the
      performance was compared to two known feature selection approaches. The results
      demonstrate that the proposed system can assist in lowering the costs with
      minimal loss in accuracy.

PMID- 28764103
TI  - Xylanase production from Thermomyces lanuginosus VAPS-24 using low cost agro
      industrial residues via hybrid optimization tools and its potential use for
      saccharification.
AB  - The xylanase production from Thermomyces lanuginosus VAPS-24 has been optimized
      using OFAT (One factor at a time) approach using agro-industrial substrates.
      Further, central composite design (CCD) has been employed to optimize various
      process parameters such as temperature (45-55 degrees C), carbon source
      concentration (1.5-2.5%), fermentation time (72-120h) and production medium pH (6
      8). Maximum xylanase yield after RSM optimization was approximately double
      (119.91+/-2.53UmL-1) than un-optimized conditions (61.09+/-0.91UmL-1). Several
      hybrid statistical tools such as Genetic Algorithm-Response Surface Methodology
      (GA-RSM), Artificial Neural Network (ANN), Genetic Algorithm-Artificial Neural
      Network (GA-ANN) were employed to obtain more optimized process parameters to
      maximize the xylanase production and observed an increase of 10.50% xylanase
      production (132.51+/-3.27UmL-1) as compared to RSM response (119.91+/-2.53UmL-1).
      The various pretreated and untreated agricultural residues were subjected to
      saccharification by using crude xylanase in which the pretreated rice straw
      yielded maximum fermentable sugars 126.89mgg-1.

PMID- 28764104
TI  - Co-fermentation of sewage sludge with ryegrass for enhancing hydrogen production:
      Performance evaluation and kinetic analysis.
AB  - The low C/N ratio and low carbohydrate content of sewage sludge limit its
      application for fermentative hydrogen production. In this study, perennial
      ryegrass was added as the co-substrate into sludge hydrogen fermentation with
      different mixing ratios for enhancing hydrogen production. The results showed
      that the highest hydrogen yield of 60mL/g-volatile solids (VS)added was achieved
      when sludge/perennial ryegrass ratio was 30:70, which was 5 times higher than
      that from sole sludge. The highest VS removal of 21.8% was also achieved when
      sludge/perennial ryegrass ratio was 30:70, whereas VS removal from sole sludge
      was only 0.7%. Meanwhile, the co-fermentation system simultaneously improved
      hydrogen production efficiency and organics utilization of ryegrass. Kinetic
      analysis showed that the Cone model fitted hydrogen evolution better than the
      modified Gompertz model. Furthermore, hydrogen yield and VS removal increased
      with the increase of dehydrogenase activity.

PMID- 28764105
TI  - Biosynthesis of keto acids by fed-batch culture of Yarrowia lipolytica WSH-Z06.
AB  - Both alpha-ketoglutarate (alpha-KG) and pyruvate (PYR) are important organic
      acids with promising applications in the food, pharmaceutical and chemical
      industries. During the production of alpha-KG by different microorganisms, PYR is
      always present as a by-product. Strategies have been applied to eliminate PYR
      accumulation since it can bring difficulties to the downstream separation
      process. However, modern separation technologies have already conquered this
      problem. Therefore, this study was aimed at simultaneously enhancing alpha-KG and
      PYR production by Yarrowia lipolytica WSH-Z06. Using a fed-batch strategy, in
      which the initial glycerol concentration was 50g.L-1, the residual glycerol
      concentration was maintained 20-30g.L-1 by constant feeding at a rate of 1.25g.L
      1.h-1. The titers of alpha-KG and PYR were increased by 9.6% and 176.8%, and
      reached 67.4g.L-1 and 39.1g.L-1, respectively. The final yield of keto acids was
      0.71g.g-1 glycerol, which is 42.0% higher than that of the optimal batch
      fermentation.

PMID- 28764106
TI  - Modelling aerobic biodegradation of atrazine and 2,4-dichlorophenoxy acetic acid
      by mixed-cultures.
AB  - The aim of this work was to study and to model the biodegradation of atrazine and
      2,4-dichlorophenoxy acetic acid by aerobic mixed cultures. Slow removal rates
      were observed when biodegrading atrazine, in spite of the initial concentrations.
      However, high removal rates were obtained when biodegrading 2,4-D, removing up to
      100mg/L in about 2months. Regarding the 2,4-D it must be highlighted that a lag
      phase appears, being its length proportional to the initial 2,4-D concentration.
      The biodegradation trends were fitted to a Monod based model and the value of the
      main parameters determined. In the case of atrazine they were umax: 0.011 1/d and
      Y: 0.53g/g and in the case of 2,4-D umax: 0.071 1/d and Y: 0.44g/g, indicating
      the higher persistence of atrazine. Once finished the experiments the microbial
      population was characterized being the major genus Pseudomonas when treating
      atrazine and Rhodococcus when treating 2,4-D.

PMID- 28764107
TI  - Membrane fouling mitigation in a moving bed membrane bioreactor combined with
      anoxic biofilter for treatment of saline wastewater from mariculture.
AB  - Membrane fouling mitigation in a novel AF-MBMBR system (moving bed membrane
      bioreactor (10L) coupled with anoxic biofilter (4L)) under high salinity
      condition (350/00) was systematically investigated. Pre-positioned AF served as a
      pretreatment induced significant decrease of suspended biomass by 85% and
      dissolved organic matters by 51.7% in subsequent MBR, which resulted in a
      reduction of cake layer formation. Based on this, sponge bio-carriers in MBMBR
      further alleviated the fouling propensity by modifying extracellular polymeric
      substances (EPS) properties. The protein component in EPS decreased from 181.4 to
      116.5mg/g MLSS, with a decline of protein/carbohydrate ratio from 4.6 to 3.4. In
      particular, elimination of hydrophobic groups like aromatic protein-like
      substance in EPS was detected. These caused the less biomass deposition on
      membrane surface, thereby alleviating membrane fouling. In summary, mitigation of
      membrane fouling in AF-MBMBR should be attributed to contributions from both pre
      positioned AF and sponge bio-carriers.

PMID- 28764108
TI  - Cellulase and xylanase production at pilot scale by solid-state fermentation from
      coffee husk using specialized consortia: The consistency of the process and the
      microbial communities involved.
AB  - Solid state fermentation is a promising technology however rising concerns
      related to scale up and reproducibility in a productive process. Coffee husk and
      a specialized inoculum were used in a 4.5L and then in 50L reactors to assess the
      reproducibility of a cellulase and hemicellulase production system. Fermentations
      were consistent in terms of cellulase production and microbial communities. The
      higher temperatures achieved when operating at 50L generated a shift on the
      microbial communities and a reduction of nearly 50% on cellulase production at
      pilot scale. In spite, an overall enzymatic production of 3.1+/-0.5FPUg-1DM and
      48+/-4Ug-1DM for FPase and Xyl activities was obtained, respectively, with low
      deviation coefficients of 16 and 19% for FPase and Xyl production. Gaseous
      emissions assessment revealed an emission factor of 2.6.10-3kg volatile organic
      compounds per Mg of coffee husk and negligible NH3, CH4 and N2O emissions.

PMID- 28764110
TI  - Urban environments alter parasite fauna, weight and reproductive activity in the
      quenda (Isoodon obesulus).
AB  - Some wildlife species are capable of surviving in urbanised environments.
      However, the implications of urbanisation on wildlife health, and public health
      regarding zoonoses, are often unknown. Quenda (syn. southern brown bandicoots,
      Isoodon obesulus) survive in many areas of Perth, Australia, despite
      urbanisation. This study investigated differences in gastrointestinal and
      macroscopic ecto-parasitic infections, morphometrics and reproductive status
      between bushland and urban dwelling quenda. 287 quenda in the greater Perth
      region were captured and sampled for faeces (to detect gastrointestinal
      parasites), blood (to detect Toxoplasma gondii antibodies), ectoparasites, and
      morphometrics. Data were analysed using multivariable logistic and linear
      regression. Most parasitic infections identified in quenda were of native
      parasite taxa that are either not known to, or considered highly unlikely to,
      infect humans or domestic animals. However, stickfast fleas (Echidnophaga spp.)
      were present at low prevalences and intensities, and Giardia spp.,
      Cryptosporidium spp. and Amblyomma spp. infections require further investigation
      to clarify their anthropozoonotic significance. Quenda captured in urbanised
      environments had differing odds of or intensity of certain parasitic infections,
      compared to those in bushland - likely attributable to quenda population density,
      and in some cases the availability of other host species or anthropogenic sources
      of infection. Urbanised environments were associated with an increase in net
      weight of adult male quenda by 189.0g (95% CI 68.6-309.5g; p=0.002; adjusted
      R2=0.06) and adult female quenda by 140.1g (95% CI 3.9-276.3g; p=0.044; adjusted
      R2=0.07), with study findings suggesting a tendency towards obesity in urbanised
      environments. Adult female quenda in bushland had increased odds of an active
      pouch (adjusted OR=4.89, 95% CI 1.7-14.5), suggesting decreased reproductive
      activity in quenda from urbanised environments. These results highlight the
      subtle, yet extensive impacts that urbanised environments may have on wildlife
      ecology, even for those species which apparently adjust well to urbanisation.

PMID- 28764109
TI  - Determining potential adverse effects in marine fish exposed to pharmaceuticals
      and personal care products with the fish plasma model and whole-body tissue
      concentrations.
AB  - The Fish Plasma Model (FPM) was applied to water exposure and tissue
      concentrations in fish collected from two wastewater treatment plant impacted
      estuarine sites. In this study we compared predicted fish plasma concentrations
      to Cmax values for humans, which represents the maximum plasma concentration for
      the minimum therapeutic dose. The results of this study show that predictions of
      plasma concentrations for a variety of pharmaceutical and personal care products
      (PPCPs) from effluent concentrations resulted in 37 compounds (54%) exceeding the
      response ratio (RR = Fish [Plasma]/1%Cmaxtotal) of 1 compared to 3 compounds
      (14%) detected with values generated with estuarine receiving water
      concentrations. When plasma concentrations were modeled from observed whole-body
      tissue residues, 16 compounds out of 24 detected for Chinook (67%) and 7 of 14
      (50%) for sculpin resulted in an RRtissue value greater than 1, which highlights
      the importance of this dose metric over that using estuarine water. Because the
      tissue residue approach resulted in a high percentage of compounds with
      calculated response ratios exceeding a value of unity, we believe this is a more
      accurate representation for exposure in the field. Predicting plasma
      concentrations from tissue residues improves our ability to assess the potential
      for adverse effects in fish because exposure from all sources is captured. Tissue
      residues are also more likely to represent steady-state conditions compared to
      those from water exposure because of the inherent reduction in variability
      usually observed for field data and the time course for bioaccumulation. We also
      examined the RR in a toxic unit approach to highlight the importance of
      considering multiple compounds exhibiting a similar mechanism of action.

PMID- 28764111
TI  - Spatial distribution, ecological and health risk assessment of heavy metals in
      marine surface sediments and coastal seawaters of fringing coral reefs of the
      Persian Gulf, Iran.
AB  - Concentrations of 13 heavy metals (Al, Fe, Mn, Zn, Cu, Cr, Co, Ni, V, As, Cd, Hg,
      Pb) in 360 reef surface sediments (0-5 cm) and coastal seawater samples from ten
      coral Islands in the Persian Gulf were analyzed to determine their spatial
      distribution and potential ecological risks. Different sediment quality indices
      were applied to assess the surface sediment quality. The mean concentrations of
      metals in studied sediments followed the order: Al > Fe > Ni > V > Mn > Zn > Cu >
      Cr > Co > As > Cd > Pb > As. Average Cd and Hg exceeded coastal background levels
      at most sampling sites. With the exception of As, concentrations of heavy metals
      decreased progressively from the west to the east of the Persian Gulf. Based on
      the Enrichment Factor (EF) and Potential Ecological Risk Index (RI),
      concentrations of V, Ni, Hg and Cd indicated moderate contamination and is of
      some concern. The mean values of heavy metals Toxic Units (TUs) were calculated
      in the following order: Hg (0.75)> Cr (0.41)> Cd (0.27)> As (0.23)> Cu (0.12)> Zn
      (0.05)> Pb (0.009). Furthermore, the mean contributing ratios of six heavy metals
      to Toxic Risk Index (TRI) values were 79% for Hg, 11.48% for Cd, 6.16% for Cr,
      3.27% for Cu, 0.07% for Zn and 0.01% for Pb. Calculated values of potential
      ecological risk factor, revealed that the risk of the heavy metals followed the
      order Cd > Pb > Ni > Cr > V > Cu > Zn. The results reflected that the level of
      heavy metals, especially Hg and Cd, are on rise due to emerging oil exploration,
      industrial development, and oil refineries along the entire Gulf. Fe, Mn, Cu, Zn,
      V and Ni concentrations in seawater were significantly higher (p < 0.05) than the
      other detected dissolved heavy metals in the sampling sites. A health risk
      assessment using the hazard quotient index (HQ) recommended by the USEPA suggests
      that there is no adverse health effect through dermal exposure, and there is no
      carcinogenic and non-carcinogenic harm to human health.

PMID- 28764112
TI  - Effects of bamboo charcoal on fouling and microbial diversity in a flat-sheet
      ceramic membrane bioreactor.
AB  - Membrane fouling is a problem in full-scale membrane bioreactors. In this study,
      bamboo charcoal (BC) was evaluated for its efficacy in alleviating membrane
      fouling in flat-sheet membrane bioreactors treating municipal wastewater. The
      results showed that BC addition markedly improved treatment performance based on
      COD, NH4+-N, total nitrogen, and total phosphorus levels. Adding BC slowed the
      increase in the trans-membrane pressure rate and resulted in lower levels of
      soluble microbial products and extracellular polymeric substances detected in the
      flat-sheet membrane bioreactor. BC has a porous structure, and a large quantity
      of biomass was detected using scanning electron microscopy. The microbial
      community analysis results indicated that BC increased the microbial diversity
      and Aminomonas, Anaerofustis, uncultured Anaerolineaceae, Anaerolinea, and
      Anaerotruncus were found in higher abundances in the reactor with BC. BC addition
      is an effective method for reducing membrane fouling, and can be applied to full
      scale flat-sheet membrane bioreactors to improve their function.

PMID- 28764113
TI  - Sugars and char formation on subcritical water hydrolysis of sugarcane straw.
AB  - Subcritical water has potential as an environmentally friendly solvent for
      applications including hydrolysis, liquefaction, extraction, and carbonization.
      Here, we report hydrolysis of sugarcane straw, an abundant byproduct of sugar
      production, in a semi-continuous reactor at reaction temperatures ranging from
      190 to 260 degrees C and at operating pressures of 9 and 16MPa. The target
      hydrolysis products were total reducing sugars. The main products of sugarcane
      straw hydrolysis were glucose, xylose, arabinose, and galactose in addition to 5-
      hydroxymethylfurfural and furfural as minor byproducts. Fourier transform
      infrared spectroscopy and thermogravimetric analysis provided additional
      information on the surface and bulk composition of the residual biomass. Char was
      present on samples treated at temperatures equal to and greater than 190 degrees
      C. Samples treated at 260 degrees C contained approximately 20wt% char, yet
      retained substantial hemicellulose and cellulose content. Hydrolysis temperature
      of 200 degrees C provided the greatest TRS yield while minimizing char formation.

PMID- 28764114
TI  - Fuzzy intelligence for investigating the correlation between growth performance
      and metabolic yields of a Chlorella sp. exposed to various flue gas schemes.
AB  - A Chlorella sp. was cultivated in a photobioreactor under different experimental
      conditions to investigate its acclimation to high-CO2 exposures. When the
      microalgae was grown under controlled flue gas sparging and optimised nutrients,
      the biomass concentration increased to 3.415+/-0.145gL-1 and the maximum protein
      yield was obtained (57.500+/-0.351% ww-1). However, when the culture was exposed
      to continuous flue gas, the lowest biomass growth (1.665+/-0.129gL-1) was noted.
      Under these conditions, high carbohydrate and lipid values were recorded
      (38.600+/-1.320% ww-1 and 30.200+/-0.150% ww-1), respectively. A Sugeno-type
      fuzzy model was employed to understand the correlation between peak biomass
      concentration (Bmax), CO2 uptake rate (qCO2), and maximum relative electron
      transport rate (rETRmax) as inputs and carbohydrate, protein, and lipid yields as
      outputs. Results of the model were in agreement with the experimental data (r2
      value >0.985).

PMID- 28764115
TI  - Study on ammonium and organics removal combined with electricity generation in a
      continuous flow microbial fuel cell.
AB  - A continuous microbial fuel cell system was constructed treating
      ammonium/organics rich wastewater. Operational performance of MFC system,
      mechanisms of ammonium removal, effect of ammonium on organics removal and energy
      output, C and N balance of anode chamber and microbial community analysis of
      anode chamber were studied. It was concluded that 0.0914kg/m3d NH4+-N and
      5.739kg/m3d COD were removed from anode chamber and simultaneous nitrification
      and denitrification (SND) occurred in cathode chamber resulting in COD, TN
      removal rate of 88.53%, 71.35% respectively. Excess ammonium affected energy
      output and the MFC system reached maximum energy output of 816.8mV and
      62.94mW/m3. In anode chamber, Spirochaetes bacterium sp., Methanobacterium
      formicicum sp. was predominant in bacteria, archaea communities respectively
      which contributed to wastewater treatment and electricity generation. This study
      showed the potential for practical application of continuous flow MFC system
      treating ammonium/organics rich wastewater and achieving electricity generation
      simultaneously.

PMID- 28764116
TI  - Amelioration and degradation of pressmud and bagasse wastes using
      vermitechnology.
AB  - This study evaluated the amelioration of pressmud (PM) and bagasse (BG) wastes by
      the vermiremediation process. The wastes were spiked with cattle dung (CD) in
      different concentrations to find out the best proportion supporting maximum
      earthworm growth and nutrients availability. The highest growth rate was observed
      in PMBG50 (282.2mg/d/worm) feed mixture. Response surface design of earthworm
      growth parameters enumerated best concentration of wastes in CD with maximum
      value of 21.81% for earthworm number, 30.86% for earthworm weight, 27.09% for
      cocoons, 29.71% for hatchlings and 34.0% for hatchlings weight. Vermicomposting
      enhanced nutrient parameters like pH (6-8%), total kjeldahl nitrogen (19-48%),
      total phosphorus (9-67%), total calcium (13-111%), while decrease in total
      organic carbon (14-32%), electrical conductivity (21-30%), C:N ratio (36-51%),
      total potassium (9-19%) and total sodium (3-21%). Heavy metals in the final
      products were found to be under safe limits. SEM micrographs were more fragmented
      which indicated maturity and stability.

PMID- 28764117
TI  - Biphasic 2-methyltetrahydrofuran/oxalic acid/water pretreatment to enhance
      cellulose enzymatic hydrolysis and lignin valorization.
AB  - A biphasic pretreatment was adopted to disturb the recalcitrant structure of
      bamboo for further enzymatic hydrolysis and to obtain easily valorized lignin by
      product. The biphasic system consisted of biomass-derived chemicals-2
      methyltetrahydrofuran and oxalic acid as well as water, and the reactions were
      conducted at 120-180 degrees C for 20min. The treatment resulted in notable
      removal of hemicelluloses and lignin. After the pretreatment, the cellulose
      conversion rate during enzymatic hydrolysis was enhanced by 6.7-fold as compared
      to the unpretreated raw material. Comprehensive analysis of the lignin product
      indicated that it exhibited representative structure (such as beta-O-4, beta-beta
      linkages) as compared to native lignin, contained a very low amount of
      contaminated sugars (0.67-2.39%), and had a relatively medium molecular weight
      (Mw 2240-3730g/mol) and good solubility in many organic solvents. This indicated
      that the lignin showed great potential application in conversion into materials
      and liquid fuels.

PMID- 28764118
TI  - Influence of biochemical composition during hydrothermal liquefaction of algae on
      product yields and fuel properties.
AB  - Hydrothermal liquefaction (HTL) of nine algae species were performed at two
      reaction temperatures (280 and 320 degrees C) to compare the effect of their
      biomass composition on product yields and properties. Results obtained after HTL
      indicate large variations in terms of bio-oil yields and its properties. The
      maximum bio-oil yield (66wt%) was obtained at 320 degrees C with a high lipid
      containing algae Nannochloropsis. The higher heating value of bio-oils ranged
      from 31 to 36MJ/kg and around 50% of the bio-oils was in the vacuum gas oil range
      while high lipid containing algae Nannochloropsis contained a significant portion
      (33-42%) in the diesel range. A predictive relationship between bio-oil yields
      and biochemical compositions was developed and showed a broad agreement between
      predictive and experimental yields. The aqueous phases obtained had high amount
      of TOC (12-43g/L), COD (35-160g/L), TN (1-18g/L), ammonium (0.34-12g/L) and
      phosphate (0.7-12g/L).

PMID- 28764119
TI  - Trans-Pacific transport of dust aerosols from East Asia: Insights gained from
      multiple observations and modeling.
AB  - East Asia is one of the world's largest sources of dust and anthropogenic
      pollution. Dust particles originating from East Asia have been recognized to
      travel across the Pacific to North America and beyond, thereby affecting the
      radiation incident on the surface as well as clouds aloft in the atmosphere. In
      this study, integrated analyses are performed focusing on one trans-Pacific dust
      episode during 12-22 March 2015, based on space-borne, ground-based observations,
      reanalysis data combined with Hybrid Single Particle Lagrangian Integrated
      Trajectory Model (HYSPLIT), and the Weather Research and Forecasting Model
      coupled with Chemistry (WRF-Chem). From the perspective of synoptic patterns, the
      location and strength of Aleutian low pressure system largely determined the
      eastward transport of dust plumes towards western North America. Multi-sensor
      satellite observations reveal that dust aerosols in this episode originated from
      the Taklimakan and Gobi Deserts. Moreover, the satellite observations suggest
      that the dust particles can be transformed to polluted particles over the East
      Asian regions after encountering high concentration of anthropogenic pollutants.
      In terms of the vertical distribution of polluted dust particles, at the very
      beginning, they were mainly located in the altitudes ranging from 1 km to 7 km
      over the source region, then ascended to 2 km-9 km over the Pacific Ocean. The
      simulations confirm that these elevated dust particles in the lower free
      troposphere were largely transported along the prevailing westerly jet stream.
      Overall, observations and modeling demonstrate how a typical springtime dust
      episode develops and how the dust particles travel over the North Pacific Ocean
      all the way to North America.

PMID- 28764120
TI  - Modelling carbon dioxide emissions from agricultural soils in Canada.
AB  - Agricultural soils are a leading source of atmospheric greenhouse gas (GHG)
      emissions and are major contributors to global climate change. Carbon dioxide
      (CO2) makes up 20% of the total GHG emitted from agricultural soil. Therefore, an
      evaluation of CO2 emissions from agricultural soil is necessary in order to make
      mitigation strategies for environmental efficiency and economic planning
      possible. However, quantification of CO2 emissions through experimental methods
      is constrained due to the large time and labour requirements for analysis.
      Therefore, a modelling approach is needed to achieve this objective. In this
      paper, the DeNitrification-DeComposition (DNDC), a process-based model, was
      modified to predict CO2 emissions for Canada from regional conditions. The
      modified DNDC model was applied at three experimental sites in the province of
      Saskatchewan. The results indicate that the simulations of the modified DNDC
      model are in good agreement with observations. The agricultural management of
      fertilization and irrigation were evaluated using scenario analysis. The
      simulated total annual CO2 flux changed on average by +/-13% and +/-1% following
      a +/-50% variance of the total amount of N applied by fertilising and the total
      amount of water through irrigation applications, respectively. Therefore, careful
      management of irrigation and applications of fertiliser can help to reduce CO2
      emissions from the agricultural sector.

PMID- 28764121
TI  - AHR and CYP1A expression link historical contamination events to modern day
      developmental effects in the American alligator.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      that initiates a transcriptional pathway responsible for the expression of CYP1A
      subfamily members, key to the metabolism of xenobiotic compounds. Toxic planar
      halogenated aromatic hydrocarbons, including dioxin and PCBs, are capable of
      activating the AHR, and while dioxin and PCB inputs into the environment have
      been dramatically curbed following strict regulatory efforts in the United
      States, they persist in the environment and exposures remain relevant today.
      Little is known regarding the effects that long-term chronic exposures to dioxin
      or dioxin-like compounds might have on the development and subsequent health of
      offspring from exposed individuals, nor is much known regarding AHR expression in
      reptilians. Here, we characterize AHR and CYP1A gene expression in embryonic and
      juvenile specimen of a long-lived, apex predator, the American alligator
      (Alligator mississippiensis), and investigate variation in gene expression
      profiles in offspring collected from sites conveying differential exposures to
      environmental contaminants. Both age- and tissue-dependent patterning of AHR
      isoform expression are detected. We characterize two downstream transcriptional
      targets of the AHR, CYP1A1 and CYP1A2, and describe conserved elements of their
      genomic architecture. When comparisons across different sites are made, hepatic
      expression of CYP1A2, a direct target of the AHR, appears elevated in embryos
      from a site associated with a dioxin point source and previously characterized
      PCB contamination. Elevated CYP1A2 expression is not persistent, as site-specific
      variation was absent in juveniles originating from field-collected eggs but
      reared under lab conditions. Our results illustrate the patterning of AHR gene
      expression in a long-lived environmental model species, and indicate a potential
      contemporary influence of historical contamination. This research presents a
      novel opportunity to link contamination events to critical genetic pathways
      during embryonic development, and carries significant potential to inform our
      understanding of potential health effects in wildlife and humans.

PMID- 28764122
TI  - Depth-distribution, possible sources, and toxic risk assessment of organochlorine
      pesticides (OCPs) in different river sediment cores affected by urbanization and
      reclamation in a Chinese delta.
AB  - Sediment cores were collected in urban (0-50 cm), rural (0-40 cm) and reclamation
      affected river (0-40 cm) environments in the Pearl River Delta. Concentrations of
      16 organochlorine pesticides (OCPs) were determined in all collected samples to
      identify the depth-distribution, possible sources and ecotoxicological risks of
      OCPs in river sediments affected by urbanization and reclamation in a Chinese
      delta. The results showed that the top 10 cm of rural river sediments had
      slightly lower concentrations of the 16 OCPs compared to urban and reclamation
      affected rivers, whereas the 30-40 cm sediment layers in the rural river showed
      higher levels of the 16 OCPs. However, higher OCPs levels were observed in the 20
      30 cm sediment layers in the urban river than in the rural and reclamation
      affected rivers. The principal OCPs in most deeper sediment layers were
      hexachlorobezene (HCB), the combination of aldrin, endrin and dieldrin
      (SigmaDRINs) and the combination of alpha-HCH, beta-HCH and gamma-HCH
      (SigmaHCHs). The predominant OCPs in surface sediments were HCB, SigmaDRINs and
      the combination of p,p'-DDD, o,p'-DDT, p,p'-DDT and p,p'-DDE (SigmaDDTs).
      Generally, OCP concentrations decreased with depth along sediment profiles at
      most sampling sites in the three types of rivers. The source analyses indicated
      that some sampling sites were still suffering from the recent use of
      hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs) and
      aldrin. According to the soil quality thresholds of China, the levels of HCHs and
      DDTs at most sampling sites were below class I criteria. Based on the sediment
      quality guideline quotient (SQGQ), the combined ecotoxicological risk of OCPs
      (gamma-HCH, dieldrin, p,p'-DDD, p,p'-DDE and p,p'-DDT) in surface sediments (0-10
      cm) was higher than deeper sediments, and the rural river sediments exhibited a
      higher combined ecotoxicological risk than the sediments in urban and reclamation
      affected rivers.

PMID- 28764123
TI  - Burden of mortality and years of life lost due to ambient PM10 pollution in
      Wuhan, China.
AB  - Ambient particulate matter (PM) has been mainly linked with mortality and
      morbidity when assessing PM-associated health effects. Up-to-date epidemiologic
      evidence is very sparse regarding the relation between PM and years of life lost
      (YLL). The present study aimed to estimate the burden of YLL and mortality due to
      ambient PM pollution. Individual records of all registered deaths and daily data
      on PM10 and meteorology during 2009-2012 were obtained in Wuhan, central China.
      Using a time-series study design, we applied generalized additive model to assess
      the short-term association of 10-MUg/m3 increase in PM10 with daily YLL and
      mortality, adjusting for long-term trend and seasonality, mean temperature,
      relative humidity, public holiday, and day of the week. A linear-no-threshold
      dose-response association was observed between daily ambient PM10 and mortality
      outcomes. PM10 pollution along lag 0-1 days was found to be mostly strongly
      associated with mortality and YLL. The effects of PM10 on cause-specific
      mortality and YLL showed generally similar seasonal patterns, with stronger
      associations consistently occurring in winter and/or autumn. Compared with males
      and younger persons, females and the elderly suffered more significantly from
      both increased YLL and mortality due to ambient PM10 pollution. Stratified
      analyses by education level (0-6 and 7 + years) demonstrated great mortality
      impact on both subgroups, whereas only low-educated persons were strongly
      affected by PM10-associated burden of YLL. Our study confirmed that short-term
      PM10 exposure was linearly associated with significant increases in both
      mortality incidence and years of life lost. Given the non-threshold adverse
      effects on mortality burden, the on-going efforts to reduce particulate air
      pollution would substantially benefit public health in China.

PMID- 28764124
TI  - Arsenic mobilization in spent nZVI waste residue: Effect of Pantoea sp. IMH.
AB  - Nanoscale zero-valent iron (nZVI) is an effective arsenic (As) scavenger.
      However, spent nZVI may pose a higher environmental risk than our initial thought
      in the presence of As-reducing bacteria. Therefore, our motivation was to explore
      the As redox transformation and release in spent nZVI waste residue in contact
      with Pantoea sp. IMH, an arsC gene container adopting the As detoxification
      pathway. Our incubation results showed that IMH preferentially reduce soluble
      As(V), not solid-bound As(V), and was innocent in elevating total dissolved As
      concentrations. MU-XRF and As MU-XANES spectra clearly revealed the heterogeneity
      and complexity of the inoculated and control samples. Nevertheless, the surface
      As local coordination was not affected by the presence of IMH as evidenced by
      similar As-Fe atomic distance (3.32-3.36 A) and coordination number (1.9) in
      control and inoculated samples. The Fe XANES results suggested that magnetite in
      nZVI residue was partly transformed to ferrihydrite, and the IMH activity slowed
      down the nZVI aging process. IMH distorted Fe local coordination without change
      its As adsorption capacity as suggested by Mossbauer spectroscopy. Arsenic
      retention is not inevitably enhanced by in situ formed secondary Fe minerals, but
      depends on the relative As affinity between the primary and secondary iron
      minerals.

PMID- 28764125
TI  - Vertical distribution and temporal dynamics of dissolved 137Cs concentrations in
      soil water after the Fukushima Dai-ichi Nuclear Power Plant accident.
AB  - Radiocesium (137Cs) migration from headwater forested areas to downstream rivers
      has been investigated in many studies since the Fukushima Dai-ichi Nuclear Power
      Plant (FDNPP) accident, which was triggered by a catastrophic earthquake and
      tsunami on 11 March 2011. The accident resulted in the release of a huge amount
      of radioactivity and its subsequent deposition in the environment. A large part
      of the radiocesium released has been shown to remain in the forest. The dissolved
      137Cs concentration and its temporal dynamics in river water, stream water, and
      groundwater have been reported, but reports of dissolved 137Cs concentration in
      soil water remain sparse. In this study, soil water was sampled, and the
      dissolved 137Cs concentrations were measured at five locations with different
      land-use types (mature/young cedar forest, broadleaf forest, meadow land, and
      pasture land) in Yamakiya District, located 35 km northwest of FDNPP from July
      2011 to October 2012. Soil water samples were collected by suction lysimeters
      installed at three different depths at each site. Dissolved 137Cs concentrations
      were analyzed using a germanium gamma ray detector. The dissolved 137Cs
      concentrations in soil water were high, with a maximum value of 2.5 Bq/L in July
      2011, and declined to less than 0.32 Bq/L by 2012. The declining trend of
      dissolved 137Cs concentrations in soil water was fitted to a two-component
      exponential model. The rate of decline in dissolved 137Cs concentrations in soil
      water (k1) showed a good correlation with the radiocesium interception potential
      (RIP) of topsoil (0-5 cm) at the same site. Accounting for the difference of
      137Cs deposition density, we found that normalized dissolved 137Cs concentrations
      of soil water in forest (mature/young cedar forest and broadleaf forest) were
      higher than those in grassland (meadow land and pasture land).

PMID- 28764126
TI  - Membrane fouling in a submerged membrane bioreactor: An unified approach to
      construct topography and to evaluate interaction energy between two randomly
      rough surfaces.
AB  - Quantitatively evaluating interaction energy between two randomly rough surfaces
      is the prerequisite to quantitatively understand and control membrane fouling in
      membrane bioreactors (MBRs). In this study, a new unified approach to construct
      rough topographies and to quantify interaction energy between a randomly rough
      particle and a randomly rough membrane was proposed. It was found that, natural
      rough topographies of both foulants and membrane could be well constructed by a
      modified two-variable Weierstrass-Mandelbrot (WM) function included in fractal
      theory. Spatial differential relationships between two constructed surfaces were
      accordingly established. Thereafter, a new approach combining these
      relationships, surface element integration (SEI) approach and composite Simpson's
      rule was deduced to calculate the interaction energy between two randomly rough
      surfaces in a submerged MBR. The obtained results indicate the profound effects
      of surface morphology on interaction energy and membrane fouling. This study
      provided a basic approach to investigate membrane fouling and interface
      behaviors.

PMID- 28764127
TI  - Ex-situ catalytic fast pyrolysis of biomass over HZSM-5 in a two-stage fluidized
      bed/fixed-bed combination reactor.
AB  - Ex-situ and in-situ catalytic fast pyrolysis (CFP) of biomass over HZSM-5 were
      compared in a two-stage fluidized-bed/fixed-bed combination reactor. Ex-situ CFP
      gave a similar carbon yield of aromatics+olefins (~20%) with in-situ CFP but
      produced much more olefins (10.3% vs. 5.8%) and less char+coke (42.7% vs. 48.4%).
      The effects of weight hourly space velocity (WHSV), carrier gas flow rate,
      pyrolysis temperature and catalysis temperature on product distribution in ex
      situ CFP were further studied. The maximum carbon yield of aromatics+olefins
      (21.7%) was obtained at pyrolysis temperature of 550 degrees C and catalysis
      temperature of 600 degrees C with the highest carrier gas flow rate (1.2L/min)
      and WHSV of 1.33h-1. Obviously less coke was generated at higher pyrolysis
      temperature. When catalysis temperature increased to 700 degrees C, ethylene and
      benzene carbon selectivities boosted to 79.4% and 60.5%, respectively.

PMID- 28764128
TI  - Using temperature-responsive zwitterionic surfactant to enhance the enzymatic
      hydrolysis of lignocelluloses and recover cellulase by cooling.
AB  - Some zwitterionic surfactants exhibit upper critical solution temperature (UCST)
      in aqueous solutions. For the zwitterionic surfactant solution mixed with
      cellulase, when its temperature is below UCST, the cellulase can be recovered by
      coprecipitation with zwitterionic surfactant. In this work, 3
      (Hexadecyldimethylammonio) propanesulfonate (SB3-16) was selected to enhance the
      enzymatic hydrolysis of lignocelluloses and recover the cellulase. After adding
      2mmol/L of SB3-16, the enzymatic digestibility of eucalyptus pretreated by dilute
      acid (Eu-DA) and by sulfite (Eu-SPORL) increased from 27.9% and 35.1% to 72.6%
      and 89.7%, respectively. The results showed that SB3-16 could reduce the non
      productive adsorption of cellulase on hydrophobic interface, while it did not
      significantly inhibit the activity of cellulase. For the solution contained 1wt%
      SB3-16 and 200mg protein/L CTec2 cellulase, 55.2% of protein could be recovered
      by cooling. The filter paper activity of the recovered cellulase was 1.93FPU/mg
      protein, which was 95.8% of its initial activity.

PMID- 28764129
TI  - Anaerobic ammonium oxidation-denitrification synergistic interaction of mature
      landfill leachate in aged refuse bioreactor: Variations and effects of microbial
      community structures.
AB  - In this work, anammox-denitrification process was verified by 15N stable isotopic
      tracing methods and variations and effects of microbial community structures were
      studied using Illumina MiSeq sequencing and Quantitative Polymerase Chain
      Reaction (qPCR). The results showed that higher nitrogen removal efficiency and
      richer microbial consortia was observed at hydraulic loading rate (HLR) of
      15L/m3.d, BOD5/TN ratio of 0.4:1, respectively. Proteobacteria, Chloroflexi,
      Acidobacteria and Firmicutes were the dominant phyla in the anamox
      denitrification biomass. The number of amx gene changed significantly during the
      HLR downshift and BOD5/TN ratio upshift period. The obtained results enhance
      understanding regarding the microbial community structures of anammox
      denitrification bacteria in aged refuse, leading to a more effective controlling
      of anammox-denitrification process.

PMID- 28764130
TI  - Sludge treatment: Current research trends.
AB  - Sludge is produced during wastewater treatment as a residue containing most
      insoluble and adsorbed soluble impurities in wastewaters. This paper summarized
      the currently available review papers on sludge treatments and proposed the
      research trends based on the points raised therein. On partition aspect, sludge
      production rate and the reduction of production rate and the fate and
      transformation of involved emergent contaminants including endocrine disrupting
      chemicals and pharmaceuticals and personal care products are widely studied. On
      release aspect, development of thermal processes on sludge with migration and
      transformation of heavy metals in sludge during treatment is a research focus.
      The use of detailed fluid and biological reaction models and advanced
      instrumentation and control systems is studied to optimize treatment
      performances. On recovery part, co-digestion of sludge with co-substrates at
      mesophilic and hyperthermophilic conditions and the recovery of phosphorus at low
      costs are research highlights.

PMID- 28764131
TI  - Effects of selected tricyclic antidepressants on early-life stages of common carp
      (Cyprinus carpio).
AB  - Despite the fact that pharmaceuticals occur in surface water in low
      concentrations, they can still have adverse effect on aquatic biota, because
      these substances are designed to have a specific mode of action even at low
      concentrations. To our knowledge, only little is known about the long-term effect
      of tricyclic antidepressant residues on non-target animals, especially fish.
      Hence, the aim of this study was to assess the effect of subchronic exposure to
      selected tricyclic antidepressants - namely, amitriptyline, nortriptyline, and
      clomipramine and their mixture - on early-life stages of common carp (Cyprinus
      carpio). Two embryo-larval toxicity tests with common carp were performed, each
      taking 30 days. For the experiment, three tricyclic antidepressants as well as
      their mixtures were tested at three different concentrations - 10, 100 and 500
      MUg/L. Hatching and mortality were recorded twice a day. In addition, samples
      were taken at regular intervals in order to record developmental stage,
      morphometric and condition characteristics and morphological anomalies. At the
      end of the test, additional samples were taken for histopathological examination
      and also for the determination of antioxidant and biotransformation enzyme
      activity and lipid peroxidation and protein carbonylation. Long-term exposure
      resulted in a significant increase in mortality, developmental retardation,
      morphological anomalies, and pathological changes in brain, heart, and cranial
      and caudal kidney. In addition, changes in antioxidant enzyme activity as well as
      increased lipid peroxidation were observed, even at the lowest tested
      concentrations. Hence, environmentally relevant concentrations of TCAs have the
      potential to cause harmful effects on early-life stages of fish.

PMID- 28764132
TI  - Use of a simple pharmacokinetic model to study the impact of breast-feeding on
      infant and toddler body burdens of PCB 153, BDE 47, and DDE.
AB  - Several studies have examined the role of breast milk consumption in the buildup
      of environmental chemicals in infants, and have concluded that this pathway
      elevates infant body burdens above what would occur in a formula-only diet.
      Unique data from Australia provide an opportunity to study this finding using
      simple pharmacokinetic (PK) models. Pooled serum samples from infants in the
      general population provided data on PCB 153, BDE 47, and DDE at 6-month
      increments from birth until 4 years of age. General population breast-feeding
      scenarios for Australian conditions were crafted and input into a simple PK model
      which predicted infant serum concentrations over time. Comparison scenarios of
      background exposures to characterize formula-feeding were also crafted. It was
      found that the models were able to replicate the rise in measured infant body
      burdens for PCB 153 and DDE in the breast-feeding scenarios, while the background
      scenarios resulted in infant body burdens substantially below the measurements.
      The same was not true for BDE 47, however. Both the breast-feeding and background
      scenarios substantially underpredicted body burden measurements. Two possible
      explanations were offered: that exposure to higher BDE congeners would
      debrominate and form BDE 47 in the body, and/or, a second overlooked exposure
      pathway for PBDEs might be the cause of high infant and toddler body burdens.
      This pathway was inhalation due to the use of PBDEs as flame retardants in
      bedding materials. More research to better understand and quantify this pathway,
      or other unknown pathways, to describe infant and toddler exposures to PBDEs is
      needed.

PMID- 28764133
TI  - Distribution of Cd, Pb and Cu between dissolved fraction, inorganic particulate
      and phytoplankton in seawater of Terra Nova Bay (Ross Sea, Antarctica) during
      austral summer 2011-12.
AB  - During the austral summer 2011-2012, the metal quotas of Cd, Pb and Cu in the
      phytoplankton of Terra Nova Bay (TNB, Antarctica) were measured for the first
      time. Evolution of all the three metal distributions between dissolved and
      particulate fractions during the season was also evaluated. Metal concentrations
      were mainly affected by the dynamic of the pack ice melting and phytoplankton
      activity. In mid-December when TNB area was covered by a thick pack ice layer and
      phytoplankton activity was very low, all the three metals were present mainly in
      their dissolved species. When the pack ice started to melt and the water column
      characteristics became ideal (i.e. moderate stratification, ice free area), the
      phytoplankton bloom occurred. Cd showed a nutrient-type behaviour with dissolved
      and particulate fractions mainly influenced by phytoplankton activity. Cd quota
      showed a mean value of 0.12 +/- 0.07 nmol L-1 (30-100% of the total particulate).
      Also Cu showed a nutrient-type behaviour, with its quota in phytoplankton varying
      between 0.08 and 2.1 nmol L-1 (20-100% of the total particulate). Pb features the
      typical distribution of a scavenged element with very low algal content (0.03 +/-
      0.02 nmol L-1, representing 20-50% of the total particulate). The vertical
      distribution of this element was influenced by several factors (e.g. pack ice
      melting, atmospheric inputs), the phytoplankton activity affecting Pb behaviour
      only partially. Metal:C ratios provide valuable information on the biological
      requirements for Cd, Pb and Cu, leading us to better understand their
      biogeochemical cycles.

PMID- 28764134
TI  - Exposure to polycyclic aromatic hydrocarbons and central obesity enhanced risk
      for diabetes among individuals with poor lung function.
AB  - Some studies have shown an association between obesity or exposure to polycyclic
      aromatic hydrocarbons (PAHs) and the risk of diabetes. This study aimed to
      investigate the interaction of obesity and urinary monohydroxy-PAHs (OH-PAHs) on
      diabetes. Individuals (n = 2716) were drawn from the baseline survey of the Wuhan
      Zhuhai Cohort Study. They completed the physical examination, measurements of
      lung function, biochemical indices and urinary OH-PAHs levels. Additive effect of
      obesity and urinary SigmaOH-PAHs levels on diabetes was assessed by calculating
      the relative excess risk due to interaction (RERI) and the attributable
      proportion (AP) due to interaction. Several urinary OH-PAHs were positively
      associated with diabetes in individuals with central obesity or normal weight (p
      < 0.05 for all). Among individuals with poor lung function, the RERI between
      urinary SigmaOH-PAHs and waist circumstance (WC, RERI: 0.866, 95% CI: -0.431,
      2.164, p = 0.192) or waist-to-height ratio (WHtR, RERI: 1.091, 95% CI: -0.124,
      2.305, p = 0.078) was found; the AP due to the interaction between urinary
      SigmaOH-PAHs and WC or WHtR was 0.383 (95% CI: -0.07, 0.80, p = 0.086) or 0.465
      (95% CI: 0.019, 0.912, p = 0.04). The results indicated that central obesity may
      enhance the effect of exposure to background PAHs on diabetes in individuals with
      poor lung function.

PMID- 28764135
TI  - Potential of miscanthus biochar to improve sandy soil health, in situ nickel
      immobilization in soil and nutritional quality of spinach.
AB  - The complex interaction of biochar (BC) with soil health reflecting properties,
      the feedstock used to prepare BC and application rate of BC in sandy soil is
      still a question for the researchers. An incubation study was conducted where
      nine different sorts of BC, each prepared from the different feedstock, were
      applied at 2% rate to evaluate their relative suitability to improve sandy soil
      health. Results revealed that BC prepared from miscanthus (MIB) significantly
      increased soil medium and fine pores, available water content (AWC), electrical
      conductivity (EC), and cation exchange capacity (CEC) while decreased soil wide
      pores, pH, bulk density (BD) and particle density (PD) compared to the rest sorts
      of BC. Later, spinach was grown in pots containing same soil but spiked with 50
      ppm nickel (Ni) and amended with 1, 2, 3, 4 and 5% rates of MIB. The results
      showed a significant increment in spinach biomass, reduction in the
      concentrations of Ni in spinach tissues and DTPA-extractable Ni with the
      increasing rate of MIB till 3% and later, no significant changes with 4 and 5%
      rates thereafter. However, significant improvement in the activities of
      antioxidant enzymes, chemical and biochemical attributes of spinach were observed
      at 5% MIB when compared to lower rates. Similarly, post-harvest soil
      physicochemical and enzymatic parameters were also significantly (P < 0.05)
      improved with increasing rates of MIB. This study implies that application of MIB
      at 5% rate can improve the nutritional quality of spinach, sandy soil health and
      can reduce Ni concentrations in spinach tissues.

PMID- 28764136
TI  - An eco-friendly approach for heavy metal adsorbent regeneration using CO2
      responsive molecular octopus.
AB  - Perennial problems of adsorption in wastewater treatment include adsorbent
      recycling, generation of waste sludge and secondary pollution because harmful
      concentrated acids, bases or strong chelators are often used for adsorbent
      regeneration and adsorbate recovery. We report, for the first time, an eco
      friendly regeneration concept demonstrated with a CO2-responsive octopus-like
      polymeric adsorbent. Various heavy metals can be scavenged at very high Qe by
      such adsorbent through coordination. Most importantly, the rapid and complete
      regeneration of the adsorbent and recovery of the heavy metal ions can be readily
      achieved by CO2 bubbling within a few minutes under mild conditions, i.e., room
      temperature and atmospheric pressure. The adsorbent can then be restored to its
      adsorptive state and reused upon removal of CO2 by simply bubbling another gas.
      This eco-friendly, effective, ultra-fast and repeatable CO2-triggered
      regeneration process using CO2-responsive adsorbent with versatile structure,
      morphology or form can be incorporated into a sustainable closed-loop wastewater
      treatment process to solve the perennial problems.

PMID- 28764137
TI  - Modeling the aqueous phase reactivity of hydroxyl radical towards diverse organic
      micropollutants: An aid to water decontamination processes.
AB  - The rate constants of the hydroxyl radical reactions (kOH) with organic
      micropollutants (OMPs) in aqueous medium are important in designing the advanced
      oxidation processes (AOPs) for their removal. In this study, a quantitative
      structure-property relationship (QSPR) model for the prediction of kOH of diverse
      and emerging OMPs was developed in accordance with the OECD guidelines. A large
      experimental data set (n = 995) comprised of compounds with kOH values ranging
      from 7.9 * 105 to 6.8 * 1010 M-1 s-1 was considered and several molecular
      descriptors were calculated. As a result, five descriptors were found to be
      important in predicting the kOH values which related to the electronegativity,
      topological polar surface area, double bonds, average molecular weight, and
      halogen atoms in the molecule. The optimal model was validated internally and
      externally and several statistical stringent parameters were derived. High values
      of the coefficient of determination (R2) and small root mean squared error (RMSE)
      in the training (0.954; 0.17) and validation (0.925; 0.14) sets indicated high
      generalization and predictivity of the developed model. Other statistical
      parameters derived from the training and validation data also supported the
      robustness of the model. The proposed model outperformed the earlier QSARs
      reported for kOH prediction. Overall, the developed QSPR model provides a
      valuable tool for an initial assessment of the susceptibility of organic
      micropollutants to AOPs.

PMID- 28764138
TI  - Coating carbon nanotubes with humic acid using an eco-friendly mechanochemical
      method: Application for Cu(II) ions removal from water and aquatic ecotoxicity.
AB  - In this work, industrial grade multi-walled carbon nanotubes (MWCNT) were coated
      with humic acid (HA) for the first time by means of a milling process, which can
      be considered an eco-friendly mechanochemical method to prepare materials and
      composites. The HA-MWCNT hybrid material was characterized by atomic force
      microscopy (AFM), scanning electron microscopies (SEM and STEM), X-ray
      photoelectron spectroscopy (XPS), termogravimetric analysis (TGA), and Raman
      spectroscopy. STEM and AFM images demonstrated that the MWCNTs were efficiently
      coated by the humic acid, thus leading to an increase of 20% in the oxygen
      content at the nanotube surface as observed by the XPS data. After the milling
      process, the carbon nanotubes were shortened as unveiled by SEM images and the
      values of ID/IG intensity ratio increased due to shortening of the nanotubes and
      increasing in the number defects at the graphitic structure of carbon nanotubes
      walls. The analysis of TGA data showed that the quantity of the organic matter of
      HA on the nanotube surface was 25%. The HA coating was responsible to favor the
      dispersion of MWCNTs in ultrapure water (i.e. -42mV, zeta-potential value) and to
      improve their capacity for copper removal. HA-MWCNTs hybrid material adsorbed 2.5
      times more Cu(II) ions than oxidized MWCNTs with HNO3, thus evidencing that it is
      a very efficient adsorbent material for removing copper ions from reconstituted
      water. The HA-MWCNTs hybrid material did not show acute ecotoxicity to the tested
      aquatic model organisms (Hydra attenuata, Daphnia magna, and Danio rerio embryos)
      up to the highest concentration evaluated (10mgL-1). The results allowed
      concluding that the mechanochemical method is effective to coat carbon nanotubes
      with humic acid, thus generating a functional hybrid material with low aquatic
      toxicity and great potential to be applied in environmental nanotechnologies such
      as the removal of heavy metal ions from water.

PMID- 28764139
TI  - Atlantooccipital Fusion: Prevalence and its Developmental and Clinical
      Correlation.
AB  - INTRODUCTION: Atlantooccipital fusion or occipitalization of atlas or
      assimilation of atlas is a rare or uncommon abnormality recorded in anatomical,
      morphological and radiological studies. It is usually associated with reduction
      in dimensions of foramen magnum leading to acute or chronic neurovascular
      compression and clinical manifestations of varying severity. Though,
      atlantooccipital fusion is rare but it is important and significant for the
      physicians and surgeons for their diagnostic and therapeutic approach. AIM: To
      know the prevalence of atlantooccipital fusion in South Asian population
      predominantly in Central India and its embryological and clinical correlation by
      reviewing literature and earlier studies. MATERIALS AND METHODS: This study
      included careful examination for the atlantooccipital fusion on total 192 human
      skulls of both genders, available in the Department of Anatomy AIIMS Raipur,
      Chhattisgarh, India, Department of Anatomy and Forensic Medicine of Gandhi
      Medical Colledge, Bhopal, Madhya Pradesh, India and Pt. Jawahar Lal Nehru
      Memorial Medical College, Raipur. Morphometric measurements of the abnormal
      skulls were done, analysed and recorded. Observations and findings of this study
      were correlated embryologically and clinically with the results and claims of
      previous studies and literature, and accordingly the conclusions were drawn.
      RESULTS: We found only two skulls with atlantooccipital fusion, in overall study
      of 192 skulls. The first skull showed incomplete atlantooccipital fusion on the
      left side with little right lateral inclination and missing posterior
      tubercle/spinous process and adjoining part of posterior arch of atlas, whereas
      the second skull showed complete atlantooccipital fusion. CONCLUSION: We conclude
      that the prevalence of atlantooccipital fusion including complete and incomplete
      fusion was 1.04%, which is higher than the proclaimed prevalence rate of 0.12% to
      0.72%, by the previous studies. In accordance with the fact that the
      atlantooccipital fusion represents a synostosis between the atlas and the
      occipital bone due to developmental abnormal segmentation of cranial part of
      paraxial mesoderm and abnormal fusion between segments of caudal occipital and
      cranial cervical sclerotomes, we would like to thereby assert that the fusion
      associated with the reduction in dimensions of foramen magnum (reduction also
      seen in our study) is definitely significant for diagnostic and therapeutic
      purposes to clinicians.

PMID- 28764140
TI  - Computed Tomographic Estimation of Relationship between Renal Volume and Body
      Weight of an Individual.
AB  - INTRODUCTION: Knowledge of normal range of size and volume of abdominal organs
      plays a vital role in clinical practices as various medical conditions affects
      the abdominal organs causing alteration in their dimensions. AIM: The present
      retrospective study was done to establish the normal range of renal volume in
      study population and to see the correlation between renal volume and body weight
      of an individual. MATERIALS AND METHODS: Computed tomographic evaluations of
      kidneys were performed on 140 kidneys of 70 individuals who had undergone
      abdominal CT scan for indications other than renal disease. We also excluded the
      patients diagnosed to have renal cysts, hydronephrosis or other renal diseases on
      CT examination. Renal length, width and depth were measured. Renal volume of both
      the kidneys was calculated by formula Kidney Volume (KV) =L/6 x Renal length (L)
      x Renal width (W) x Renal depth (D). Various body parameters like age, weight,
      sex were also recorded in the data sheet. RESULTS: Mean renal volume for the
      right kidney was 83.26+/-18.33 cm3 for females (33 females out of 70) and
      103.92+/-23.27 cm3 for males (37 males out of 70). However, mean renal volume for
      the left kidney was 89.17+/-19.41 cm3 in females and 106+/-26.79 cm3 in males.
      Left renal volume was apparently more than right renal volume, though
      statistically insignificant. In males, mean kidney volume was found to be 104.96
      cm3 whereas in females, it was found to be 86.21 cm3. Kidney volume was found to
      be significantly greater in males than females among study population (t=3.79,
      p=0.0001). Renal volume significantly correlated with age and body weight of an
      individual. CONCLUSION: This study is a sincere attempt to establish a normograms
      of renal volume in study population. For the clinical assessment of renal
      pathologies, knowledge of renal volume is a vital parameter. In study group, most
      significant parameter associated with renal volume is body weight which can be
      used as an adjunct while evaluating renal pathological conditions. Of all the
      radiological imaging techniques, abdominal coronal computed tomography scan
      provides most accurate renal measurements.

PMID- 28764142
TI  - Sex Determination by Biometry of Anterior Features of Human Hip Bones in South
      Indian Population.
AB  - INTRODUCTION: Sex determination is the first step in establishing the identity of
      skeletal remains. Many studies included biometry of posterior features of hip
      bone. Very few studies are reported involving the biometry of anterior features
      of the hip bone. Anterior features of hip bone are important especially, if there
      is damage to the posterior features of hip bone in cases involving deliberate
      disfigurement of the body to resist identification of the crime in medicolegal
      cases. AIM: The present study was done to evaluate the effectiveness of anterior
      border parameters of the hip bone for prediction of sex using discriminant
      function analysis in South Indian population. MATERIALS AND METHODS: A total of
      206 dry bones were used (121 male and 85 female) and parameters like the distance
      between pubic tubercle and anterior rim of acetabulum, vertical acetabular
      diameter, transverse acetabular diameter, and the distance between pubic tubercle
      to highest point on the iliopubic eminence were measured using Vernier calipers.
      Normally distributed variables were compared using Students t-test to analyse the
      significance. RESULTS: There was significant difference between the male and
      female hip bones of the observed variables with p-value less than 0.05. In
      parameters like the distance between pubic tubercle to anterior rim of acetabulum
      and distance between the highest points on iliopubic eminence to pubic tubercle;
      the values were more in female when compared to males. In parameters like
      vertical and transverse acetabular diameters; the values in males were more when
      compared to females. CONCLUSION: These parameters of hip bone can be utilised for
      sex determination in South Indian population.

PMID- 28764141
TI  - Morphological Study of Human Liver and Its Surgical Importance.
AB  - INTRODUCTION: Liver is the largest abdominal organ located in right
      hypochondrium, epigastrium and left hypochondrium in upper abdominal cavity.
      Although the segmental anatomy of the liver has been extensively researched, very
      few studies have dealt with surface variations of the liver. The major fissures
      are important landmarks for interpreting the lobar anatomy and locating the liver
      lesions. AIM: To determine gross anatomical variations of liver and their
      clinical and surgical implications. MATERIALS AND METHODS: Present morphological
      study was conducted on 80 formalin-fixed livers which were observed for the study
      in the Department of Anatomy, Baroda Medical College, Vadodara, Gujarat, India.
      Different variations in lobes, fissures and accessory lobes, decrease in size of
      lobes, lobar atrophy and any other variations on the surface of the livers were
      observed. The liver specimens were also classified according to netter's six
      types of liver variations. RESULTS: Total 80 cadaveric livers were studied. Out
      of which 14(17.5%) livers were normal and 66(82.5%) were abnormal. Out of 66,
      abnormal fissures were in 28(35%), abnormal lobes were in 29(36.25%), large
      papillary process in 1(1.25%), Pons hepatis joining the left lobe with quadrate
      lobe in 1(1.25%) liver, deep renal impression and corset constriction observed in
      1(1.25%) and deep diaphragmatic groove were observed in 6(7.5%). CONCLUSION: The
      findings of our study may be helpful for surgeons and radiologists to avoid
      possible errors in interpretations and subsequent misdiagnosis, and to assist in
      planning appropriate surgical approaches.

PMID- 28764143
TI  - Prevalence of Flexible Flat Foot in Adults: A Cross-sectional Study.
AB  - INTRODUCTION: Flat foot (pes planus) is a commonly observed disorder in clinical
      practice. The height of Medial Longitudinal Arch (MLA) determines the degree of
      pes planus. Majority of the previous studies on prevalence of flexible flat foot
      were done among children. AIM: The present study was undertaken to determine the
      prevalence of flexible flat foot among 18-21-year-old Indian adults using
      Navicular Drop Test (NDT) which is regarded as reliable and valid method to
      characterise MLA. MATERIALS AND METHODS: The present study was a cross-sectional
      study in which Brody's Navicular Drop Test was performed in five hundred healthy
      subjects (250 males and 250 females) aged 18-21-year-old. Navicular Drop (ND) of
      >= 10 mm was regarded as flexible flat foot. Statistical analysis was done using
      SPSS version 23.0. RESULTS: The prevalence of flexible flat foot was 13.6% (for
      males-12.8%; for females-14.4%). The median with Inter Quartile Range (IQR) for
      ND among males was 6 mm (4-8) and 6 mm (4-9) for right and left foot
      respectively. The median with IQR for ND among females was 6mm (4-10) and 7mm (3
      8) for right & left respectively. The correlation of Right Side Navicular Drop
      (RND) with height and weight was significant, but insignificant correlation was
      found between RND and BMI. The correlation of Left Side Navicular Drop (LND) with
      height, weight and BMI of individuals was statistically not significant. The
      difference between the ND of males and female group was statistically not
      significant. CONCLUSION: The present study quantified the prevalence of flexible
      flat foot and gender wise normative values of ND among 18-21-year-old Indian
      adults. The information obtained by this study will be useful in the field of
      orthopaedics.

PMID- 28764144
TI  - Variant Anatomy of the Hepatic Vasculature: Importance in Hepatobiliary
      Resections.
AB  - A variant anatomy of the hepatic vasculature has a clinically significant role in
      hepatobiliary transplantation, resection, tumour embolisation as well as in
      extrahepatic abdominal surgeries involving the stomach, pancreas or gall bladder.
      During routine cadaveric dissection, we observed a case of unusually small
      calibre hepatic artery proper. An accessory hepatic artery was seen emerging from
      the superior mesenteric artery to the right hepatic lobe along with an accessory
      hepatic vein from the right hepatic lobe that drained directly into the inferior
      vena cava. Such accessory hepatic vessels complicate and necessitate an
      alteration of surgical methodology during resection of hepatic lobes.
      Preoperative knowledge of variant hepatic vasculature is crucial for minimising
      the iatrogenic injury and facilitating successful abdominal surgeries.

PMID- 28764145
TI  - Effect of Fluoxetine on the Hippocampus of Wistar Albino Rats in Cold Restraint
      Stress Model.
AB  - INTRODUCTION: Stress has been known to be a potential modulator of learning and
      memory. Long term stress can lead to depression. Fluoxetine is a selective
      serotonin reuptake inhibitor group of drug used in the treatment of depression.
      AIM: The present study was conducted to evaluate the potential of Fluoxetine on
      cold restraint induced stress in the hippocampus of Wistar rats. MATERIALS AND
      METHODS: A total of 18 male wistar albino rats were divided randomly into three
      groups (n=6). Group 1 was the control group which were kept in normal laboratory
      conditions. Group 2 was the negative control group which were given cold
      restraint stress for period of four weeks. Group 3 was the experimental group,
      where the animals were pretreated with fluoxetine 10 mg/kg for a period of one
      week followed by cold restraint stress for 30 minutes and cotreated with
      fluoxetine 10 mg/kg for a period of four weeks. The whole study was done for a
      period of five weeks followed by behavioural studies and subsequently sacrificed
      with removal of brain for various histological, Immunohistochemical (IHC),
      neurochemical and antioxidant analysis. The values were expressed as Mean+/-SEM.
      One-way analysis of variance followed by Tukey's multiple comparisons test was
      used for the comparison of means. A probability of 0.05 and less was taken as
      statistically significant using Prism Graphpad software version 6.01. RESULTS:
      The results show there was significant improvement in the Morris water maze test
      after treatment with fluoxetine in Group 2. Similar results were also noted in
      the levels of neurotransmitters and antioxidant levels in brain and also in the
      number of cells counted in IHC and histological studies by H&E when Group 3 was
      compared with Group 2. The treatment reversed the damage in Group 2 which was
      comparable with the control group. CONCLUSION: The results revealed that
      administration of fluoxetine 10 mg/kg given orally has a potential antistressor
      effect by improving the neurogenic and neuroprotective effect on the cold
      restraint stress induced hippocampal damage.

PMID- 28764146
TI  - Role of Anaemia and Magnesium Levels at the Initiation of Tuberculosis Therapy
      with Sputum Conversion among Pulmonary Tuberculosis Patients.
AB  - INTRODUCTION: Both pulmonary Tuberculosis (TB) and anaemia are prevalent in
      India. Magnesium levels also influence TB. There is limited and inconsistent
      literature on the association among anaemia, serum magnesium levels and sputum
      conversion during tuberculosis treatment. AIM: To study the effect of anaemia and
      serum magnesium levels on sputum conversion in pulmonary TB patients. MATERIALS
      AND METHODS: One hundred each of newly diagnosed sputum smear positive Pulmonary
      Tuberculosis (PTB), sputum smear negative PTB patients initiated on Directly
      Observed Treatment Short Course chemotherapy (DOTS) and healthy age and sex
      matched controls were recruited in the study. Patients were followed up
      prospectively until completion of first two months of intensive phase. Patients
      were evaluated before initiation of TB treatment by performing the complete blood
      counts with peripheral blood smear, serum biochemistry, serum iron, serum
      magnesium, serum ferritin and microscopic examination of sputum. After giving two
      months of Antitubercular Therapy (ATT), sputum smears were re-examined for
      presence of acid fast bacilli. Haemoglobin values less than 13 g/dl in males or
      12 g/dl in females was defined as anaemia. Mean and Standard deviations were
      calculated. Independent t-test was used to compare between the groups. RESULTS:
      Serum iron and serum ferritin was significantly lower in sputum positive PTB as
      compared to sputum negative PTB and controls. Anaemia was present in 162 (81%)
      patients of the study PTB cases. About 60% of anaemia in sputum positive cases
      was iron deficiency anaemia. Serum magnesium level was significantly lower in
      sputum positive PTB as compared to sputum negative PTB and controls though not in
      hypomagnesemic range. Delayed sputum smear conversion occurred in 12 (12%) sputum
      positive PTB patients. Of these, eight had severe iron deficiency anaemia, four
      with moderate anaemia. All 12 delayed sputum smear conversion had serum magnesium
      levels < 1.7 mg/dl (below normal reference range) (mean 1.42 +/-0.22 mg/dl).
      CONCLUSION: Sputum was found to be positive even after two months of ATT course
      because of baseline anaemia and lower levels of serum magnesium. Further
      multicentric studies are warranted to study mechanisms for TB associated anaemia
      and possible role of intervention for anaemia in TB patients. One needs to find
      out the mechanisms behind the role of anaemia and lower magnesium levels in
      delaying the sputum smear conversion in order to lay the foundation of effective
      interventions. Randomized controlled trials are warranted to generate higher
      levels of evidences to support our findings.

PMID- 28764147
TI  - Study of Vitamin D Receptor Gene Polymorphism (FokI, TaqI and ApaI) Among
      Prostate Cancer Patients in North India.
AB  - INTRODUCTION: Incidence of prostate cancer is rising worldwide. Multiple factors
      have been suggested for the aetiology of prostate cancer including ethnic,
      genetic and diet. Vitamin D (calcitriol) has been shown to have role in cell
      growth and differentiation and its deficiency is implicated as one of the
      aetiological factors in prostate cancer. Prostatic epithelial cells express
      Vitamin D Receptor (VDR) as well as 1alpha- hydroxylase enzyme that are required
      for the synthesis of calcitriol and its action. Polymorphism in VDR gene has been
      associated with prostate cancer in some epidemiological studies; but, there is
      paucity of information in the Indian context. AIM: The present study was aimed to
      explore the association of VDR gene polymorphism with the development of prostate
      cancer. MATERIALS AND METHODS: Three Single Nucleotide Polymorphisms (SNP) sites
      viz., FokI, TaqI and ApaI were analysed in 120 cases of prostate cancer which
      were compared with their 120 healthy first degree relatives and 120 non-related
      controls in the Department of Biochemistry in collaboration with the Department
      of Urology. RESULTS: Analysis showed significantly decreased incidence of Tt and
      Aa genotype in prostate cancer patients as compared to healthy non-relative
      controls (p=0.016 and 0.043 respectively). As compared to first degree relatives,
      incidence of Tt genotype is significantly lower in cases (p=0.005). No
      significant association was found with FokI polymorphism. CONCLUSION: This study
      suggests the protective role of heterozygous genotypes of TaqI and ApaI
      polymorphism against the development of prostate cancer.

PMID- 28764148
TI  - The Anthropometric Correlates for the Physiological Demand of Strength and
      Flexibility: A study in Young Indian Field Hockey Players.
AB  - INTRODUCTION: Optimal strength and flexibility are essential for performance
      enhancement and injury prevention in hockey, and anthropometry is known to
      influence these parameters. AIM: To find anthropometric correlates for strength
      and flexibility score in young Indian field hockey players. MATERIALS AND
      METHODS: Thirteen female and 19 male subjects volunteered for the study. Selected
      anthropometric variables: lengths, breadths, girths and body composition;
      strength and sit and reach score were measured for each subject. RESULTS: Males
      were taller, leaner and stronger with longer upper limbs and broader chests. With
      few exceptions, taller, heavier and leaner players with longer trunks and limbs,
      broader chest and hip, and bulkier arms and lower limbs had stronger grip, back,
      upper and lower limbs. Heavier and taller players with longer trunk and more
      percentage of body fat were more flexible. Also, the stronger players had more
      percentage body fat and body mass index, which might be due to the strong
      positive correlation of percentage body fat and body mass index with fat free
      mass. CONCLUSION: Anthropometric variables, especially heights, breadths and body
      composition, show significant correlation with strength and flexibility, and
      hence may serve as monitoring tool and for talent identification.

PMID- 28764149
TI  - Need for Changes in the Practical Physiology Curriculum of Medical
      Undergraduates.
AB  - INTRODUCTION: Physiology is one of the foundation sciences for the medical
      curriculum. It forms the basis of all life sciences. Physiology practical classes
      in India are divided into three sections: exercises in haematology, exercises on
      humans and experiments on amphibians. Faculty and students of medical schools in
      India are of the opinion that animal experiments should be discontinued, that the
      curriculum in experimental physiology and pharmacology needs to be updated, that
      the same understanding of topics could be obtained by using alternative methods
      and that there is an urgent need to introduce alternatives of animal experiments.
      AIM: To assess the need for changes in the practical physiology curriculum of
      medical undergraduates. MATERIALS AND METHODS: The study was conducted among 300
      MBBS, second and third professional students using a semi-structured
      questionnaire. The questionnaire consisted of two sections: the first section was
      based on the current experimental physiology curriculum regarding the relevance
      of topics taught in haematology, amphibian and human practical classes. In the
      second section, the opinion was also sought regarding introduction of new topics
      related to recent advances in clinical physiology and basic clinical skills.
      RESULTS: More than 60% of the students marked most of the haematology experiments
      useful. All the amphibian practicals were considered irrelevant/not useful by
      more than 75% of the students. Regarding the human experiments, more than 70% of
      the students marked useful. More than 65% students were of the opinion that basic
      clinical skills should be introduced at undergraduate level. More than 50%
      students favoured introduction of topics from recent advances in physiology.
      CONCLUSION: The present study concludes that there is an imperative need to
      implement radical changes in the experimental physiology curriculum which should
      be in consonance with patient care for the doctors of tomorrow to render better
      health service.

PMID- 28764150
TI  - Modulation of Lung Function by Increased Nitric Oxide Production.
AB  - INTRODUCTION: Cigarette smoking reduces endogenous Nitric Oxide (NO) production
      by reducing Nitric Oxide Synthase (NOS) activity, which is one of the probable
      reason for increased rate of pulmonary diseases in smokers. Nitric oxide/oxygen
      blends are used in critical care to promote capillary and pulmonary dilation to
      treat several pulmonary vascular diseases. Among several supplements, the highest
      NOS activation has been proved for garlic with its unique mechanism of action.
      AIM: To investigate the effect of dietary supplementation of NO producing garlic
      on pulmonary function of smokers. MATERIALS AND METHODS: The study was conducted
      on 40 healthy non-smoker (Group A) and 40 chronic smoker (Group B) males with
      matched age, height and weight. The pulmonary function tests- Forced Vital
      Capacity (FVC), Forced Expiratory Volume in one second (FEV1), FEV1/FVC ratio and
      Peak Expiratory Flow Rate (PEFR) were performed in non-smokers (Group A), smokers
      (Group B) and smokers after supplementation of approximately 4 gm of raw garlic
      (2 garlic cloves) per day for three months (Group C). Endogenous NO production
      was studied in smokers before and after garlic supplementation and in non-smokers
      without supplementation. The data obtained were compared between the groups using
      unpaired student's t-test. The p-value considered significant at <0.05. RESULTS:
      Our results showed that FVC, FEV1, FEV1/FVC ratio and PEFR were reduced
      significantly along with a significant decreased NOS activity among smokers
      (Group B) when compared with non-smokers (Group A). Garlic supplementation
      significantly improved the pulmonary function tests in Group C in comparison to
      Group B by increasing NOS activity. CONCLUSION: Dietary supplementation of
      garlic, which might be by increasing NOS activity, has significantly improved
      pulmonary functions in smokers.

PMID- 28764151
TI  - Evaluation of the Female Patients with Subclinical Hypothyroidism by Brainstem
      Auditory Evoked Potentials: Case-Control Study.
AB  - INTRODUCTION: Hypothyroidism, a common endocrinological disorder is quite
      prevalent in its subclinical state in the adult population. Nervous system
      involvement is frequent in hypothyroidism with documentation of peripheral and
      central conduction delays as abnormal latency prolongations in Brainstem Auditory
      Evoked Potential (BAEP) records. Subclinical hypothyroidism however, has been
      less extensively studied for investigating the involvement of the auditory
      functions. AIM: To assess the auditory functions and Central Nervous System (CNS)
      involvement in the patients with subclinical hypothyroidism by recording BAEP.
      MATERIALS AND METHODS: The study comprised of 50 females (25 females with
      subclinical hypothyroidism and 25 age-matched healthy females) in the age-group
      of 30-50 years. BAEP absolute and Interpeak Latencies (IPLs) (I, III and V, I
      III, III-V and I-V) were compared between the two groups by unpaired t-test. The
      p<0.05 was considered as statistically significant. RESULTS: Mean BAEP absolute
      latencies (III and V) increased in the subjects with subclinical hypothyroidism
      as compared to controls (p<0.001) (both the ears) and wave I absolute latency
      also increased with p<0.001 (both the ears) by unpaired t-test. Among IPLs
      (interpeak latencies), III-V and I-V IPLs exhibited increase (p<0.01), while I
      III IPL did not vary with statistical significance (both the ears) in the two
      groups. CONCLUSION: Patients with subclinical hypothyroidism were found to
      demonstrate central as well as peripheral auditory pathway affections. BAEPs can
      prove valuable and sensitive tests to detect involvement of the CNS and auditory
      dysfunctions earlier in hypothyroidism.

PMID- 28764152
TI  - Effect of BMI, Body Fat Percentage and Fat Free Mass on Maximal Oxygen
      Consumption in Healthy Young Adults.
AB  - INTRODUCTION: Maximal oxygen consumption (VO2max) is an important measure of
      cardiorespiratory capacity of an individual at a given degree of fitness and
      oxygen availability. Risk of cardiovascular diseases increases with increasing
      degree of obesity and a low level of VO2max has been established as an
      independent risk factor for cardiovascular mortality. AIM: To determine VO2max in
      young adults and to find its correlation with Body Mass Index (BMI), Body Fat%
      and Fat Free Mass (FFM). MATERIALS AND METHODS: Fifty four (male=30, female=24)
      healthy young adults of age group18-25 years after screening by Physical Activity
      Readiness Questionnaire (PAR-Q) participated in the study. Height was measured by
      stadiometer. Weight was measured by digital weighing scale with 0.1 kg
      sensitivity. Body fat% was measured by Bioelectrical Impedance Analysis (BIA)
      method. FFM was calculated by subtracting fat mass from the body weight. VO2max
      (mL.kg-1.min-1) was obtained by Submaximal Exercise Test (SET) by first two
      stages of Bruce Protocol with the basis of linear relationship between Heart Rate
      (HR) and oxygen consumption (VO2). Data were analysed statistically in GraphPad
      Prism software version 6.01 for windows. RESULTS: VO2max (mL.kg-1.min-1) of male
      (43.25+/-7.25) was significantly (p<0.001) higher than female (31.65+/-2.10). BMI
      showed weak negative correlation (r= -0.3232, p=0.0171) with VO2max but Body Fat%
      showed strong negative correlation (r= -0.7505, p<0.001) with VO2max. FFM
      positively correlated (r=0.3727, p=0.0055) with VO2max. CONCLUSION: Increased
      body fat is associated with decreased level of VO2max in young adults. Obesity in
      terms of Fat% is a better parameter than BMI for prediction of low VO2max.

PMID- 28764153
TI  - Correlation of Adiposity Indices with Electrocardiographic Ventricular Variables
      and Vascular Stiffness in Young Adults.
AB  - INTRODUCTION: Excess adiposity constitute an important public health problem
      because of the associated increased risk of hypertension, coronary heart disease,
      type 2 diabetes and other disorders. Not only the contribution of general
      measures of adiposity but also central measures of adiposity have been observed.
      AIM: To compare and correlate the central and general adiposity indices with
      ventricular electrocardiographic variables and vascular stiffness indices in
      normal, overweight and obese young adults. MATERIALS AND METHODS: This was a
      cross-sectional study. Nearly ninety subjects were enrolled and were divided into
      30 normal weight, 30 overweight and 30 obese group based on the BMI
      classification of WHO for Asian population with their age ranging from 18-25
      years. Waist and hip circumferences were measured using stretchable tape. Two
      novel indices-conicity index and abdominal volume index were calculated using
      standard formula. ECG and pulse wave were recorded using the Physiopac - Medicaid
      systems. Statistical analysis was done using SPSS version 19.0 software. ANOVA
      test was done to compare the variables among three groups. Pearson's correlation
      coefficients were applied to establish the correlations between variables.
      RESULTS: In our study Body Mass Index (BMI) and Conicity Index (CI) was
      significantly and strongly correlated with the ventricular electrocardiographic
      variables especially with QRS duration, QTc interval and with vascular stiffness
      indices. These indices can be used to assess the electrocardiographic
      abnormalities and vascular stiffness status. CONCLUSION: Excess adipose tissue in
      young adults was closely linked to ventricular depolarization and repolarization
      abnormalities and also to increased vascular stiffness. Adiposity indices in
      particular (BMI, CI) provide a simple and non invasive approach to assess these
      abnormalities at the earliest in order to prevent future complications.

PMID- 28764154
TI  - Effect of Agonist and Antagonist on the In Vitro Contractility of Inflamed
      Vermiform Appendix.
AB  - INTRODUCTION: Appendicitis poses a great health problem worldwide. Previous
      studies demonstrated structural damage to neuronal network and interstitial cell
      of Cajal in appendicitis. Above observations suggest for the alterations in
      appendicular motility/contractility in appendicitis. But the mechanisms involved
      in mediating the contractility in inflamed vermiform appendix is not known till
      date. AIM: The present in vitro study was performed to find out the mechanisms
      responsible for contractility in the inflamed human vermiform appendix. MATERIALS
      AND METHODS: Contractions of the longitudinal muscle strips of inflamed appendix
      were recorded in vitro at 37+/-0.5 degrees C. Control contractions were recorded
      for 30 min after an initial tension of 0.5 gram. Initially dose-response
      experiments of agonists (acetylcholine, serotonin and histamine) were performed
      separately and the dose that produced maximum contraction was determined with
      each agonist. This maximal dose of agonist was used to elicit contractions in
      next series of experiments before and after pre-treatment with appropriate
      antagonists like atropine, ondansetron (5-HT3 antagonist) and chlorpheniramine
      maleate respectively. RESULTS: Acetylcholine (ACh) and serotonin (5-HT) elicited
      maximum amplitude of contraction at 10 uM and 1 uM concentration respectively.
      These contractions were significantly blocked by prior exposure of muscle strips
      with atropine (100 uM) and ondansetron (10 uM). Histamine produced very low
      amplitude of contractions in comparison to ACh or 5-HT and did not exhibit dose
      response relations. The histamine induced contractions were blocked by H1
      antagonist chlorpheniramine maleate (100 uM). CONCLUSION: The observations
      suggested that the contractility of longitudinal muscle strips of inflamed
      vermiform appendix in human beings was predominantly mediated by muscarinic and
      serotonergic (5-HT3) mechanisms, whereas, histaminergic mechanisms played a minor
      role in mediating the contractility.

PMID- 28764155
TI  - Role of Endocannabinoids on Neuroinflammation in Autism Spectrum Disorder
      Prevention.
AB  - Autism Spectrum Disorder (ASD) disease has become a mounting socio-economical
      alarm around the world. Neuroinflammtion had been shown in postmortem brain
      specimens from ASD patients. The Endocannabinoids System (ES) consists of a
      family of locally produced, short-lived, endogenous, phospholipid-derived
      agonists (endocannabinoids) that control energy balance and body composition. The
      growing number of medical benefits of ES, such as their ability to regulate
      processes like neuroinflammation, neurogenesis and memory, raise the question of
      their potential role as a preventive treatment of ASD. To test this hypothesis,
      basic and clinical studies allow us a thorough investigation of the role of ES in
      the pathogenesis of ASD. This hypothesis will help to understand the mechanism of
      ES and its role in ASD.

PMID- 28764156
TI  - Improved Serodiagnostic Sensitivity of Strip Test for Latent Tuberculosis.
AB  - INTRODUCTION: Diagnosis of Latent Tuberculosis Infection (LTBI) is difficult due
      to no clinical manifestations. Cases of LTBI are mostly sputum negative. The
      World Health Organization recommends the Tuberculin Skin Test (TST) as the
      current diagnostic standard for LTBI. Our previously developed serologic strip
      test for LTBI detection had suboptimal sensitivity. Additional
      Mycobacteriumtuberculosis (MTB) latency-associated antigens may improve the
      detection rate of LTBI. AIM: The present study aimed to optimize sensitivity of
      existing strip test. MATERIALS AND METHODS: A combination of recombinant latency
      proteins Rv2029c, Rv2031c, Rv2032, Rv2627c, Rv3133c, and Rv3716c was used to
      prepare the strips and evaluate the performance with the sera of patients in four
      well-classified categories: LTBI, active pulmonary TB, healthy TB contacts and
      other non-TB diseases. RESULTS: A total of 91 serum samples from various clinical
      categories were screened with the strips. Among clinically diagnosed LTBI
      patients, strip test yielded a sensitivity of 75.0%. Among clinically diagnosed
      non-LTBI subjects, strip test yielded 88.1% specificity. The diagnostic positive
      and negative predictive values for strip test in reference to various clinical
      contexts were 77.4% and 86.7%, respectively. CONCLUSION: Addition of the six
      potential latency proteins could improve the diagnostic performance of existing
      strip test for LTBI. The use of suitable immunodominant antigens could maximize
      sensitivity in the diagnosis and differentiate MTB infection status.

PMID- 28764157
TI  - Seroepidemiology of Spotted Fever Rickettsiosis in Uttar Pradesh: A Prospective
      Study.
AB  - INTRODUCTION: Spotted Fever Rickettsiosis (SFR), an acute febrile illness caused
      by Rickettsia rickettsii, R. conorii and R. akari which is associated with
      considerable morbidity and mortality. SFR is one of the most covert emerging
      infections of the present time which is prevalent in various parts of India as
      shown by the increase in the number of clinically diagnosed patients in various
      states except Uttar Pradesh. AIM: To diagnose SFR in clinically suspected
      patients using serological tests and recognition of common epidemiologic
      situations and clinical manifestations of SFR in the state of Uttar Pradesh.
      MATERIALS AND METHODS: Patients of all age groups presented with a diagnosis of
      Pyrexia of Unknown Origin (PUO) from May 2013 to February 2015 were evaluated.
      Testing was done using a nonspecific Weil felix test followed by more specific
      Enzyme Linked Immunosorbent Assay (ELISA) and a gold standard Immunofluorescence
      Assay (IFA) test for specific IgM antibodies against Rickettsia conorii. The data
      was statistically analysed on Graph Pad Prism (5.0) software by using Chi-square
      test. RESULTS: Of the 432 patient samples tested by non specific Weil felix test,
      200 (46.29 %) samples showed titre 1:80 or more and were taken as positive.
      Similarly out of the 432 blood samples tested by both ELISA and IFA based test
      against Rickettsiaconorii IgM antibody, only 115 (26.62%) samples were found to
      be positive and these samples were also positive by Weil felix. The common
      symptoms noted were fever, hepatomegaly, thrombocytopenia, lymphadenopathy and
      rashes, nausea followed by icterus, cyanosis, headache, oedema and abdominal
      pain. Eschar was found in only four (3.4%) patients. We also found that 31
      patients with SFR also had associated co-infections like typhoid, malaria, dengue
      and hepatitis. CONCLUSION: Our findings demonstrated that Weil Felix test can
      fill in as an underlying yet not sole strategy to perceive and analyse
      rickettsial ailments, as it needs specificity. So, it may be used to assess the
      burden in the area and later on other tests like ELISA or IFA can be added, as
      these are more specific diagnostic tests. Further, our results also showed that
      if a patient tests positive for the more common endemic infections, we must test
      for rickettsiosis so that appropriate treatment could be administered.

PMID- 28764158
TI  - Salivary Anti-50 kDa Antibodies as a Useful Biomarker for Diagnosis of Typhoid
      Fever.
AB  - INTRODUCTION: Typhoid fever remains a scourge of humanity, especially in
      developing and under-developed countries due to poor sanitation and food hygiene.
      Diagnostic methods available for detection of this disease are not satisfactory
      due to a lack of sensitive, specific, rapid and convenient diagnostic test kits
      available in the market. AIM: To evaluate the feasibility of a Dot-EIA method for
      Ig-class specific salivary antibody detection for diagnosis of typhoid fever.
      MATERIALS AND METHODS: Paired saliva and serum samples were collected in the year
      2010 from patients and normal volunteers in Hospital Universiti Sains Malaysia,
      Kelantan, Malaysia, which is endemic for typhoid fever. A total of 11 culture
      confirmed typhoid fever patients, 43 non-typhoid fever patients and 53 normal
      human control subjects were evaluated for antibodies against a 50 kDa antigen
      specific for Salmonella Typhi using Dot-EIA. RESULTS: Ig class-specific screening
      of the test samples showed a higher sensitivity for IgA (90.9%) compared to
      either IgG (72.7%) or IgM (72.7%) antibodies in saliva, but for serum, IgG
      (90.9%) had a higher degree of sensitivity compared to IgA (36.4%) and IgM
      (63.6%). Combining all isotypes (IgA, IgG or IgM), serum showed a higher
      sensitivity (100.0%) compared to saliva (90.9%). Also, the specificity for serum
      (100.0%) was much higher than saliva (85.4%). CONCLUSION: Salivary IgA anti-50kDa
      antibody was found to be more suitable biomarker for routine screening, whereas
      serum IgG was more suitable for confirmatory test as it has higher specificity.
      Nevertheless, salivary IgA Dot-EIA is a convenient method for rapid testing, such
      as for Point-of-Care Diagnostics (POCD) and field epidemiological studies, due to
      its non-invasive nature and ease of use.

PMID- 28764159
TI  - Otomycosis in a Rural Community Attending a Tertiary Care Hospital: Assessment of
      Risk Factors and Identification of Fungal and Bacterial Agents.
AB  - INTRODUCTION: Otomycosis is one of the frequently encountered fungal infections
      of external auditory canal, commonly seen in tropical and subtropical regions of
      the world. Various host (local, systemic) and environmental factors can
      predispose a person to otomycosis. Although clinical presentations along with
      otoscopic findings of the patients are well suggestive of fungal infection,
      proper identification of causative agents is mandatory in order to prevent
      recurrences and complications. AIM: To define the aetiology of clinically
      diagnosed otomycosis in rural population, to derive association of risk factors
      with otomycosis, to isolate and identify fungal and bacterial agents and to
      analyze the association between them. MATERIALS AND METHODS: A prospective study
      was conducted in the Department of Microbiology and Department of Ear, Nose and
      Throat (ENT), SGT hospital over eight months period. A total of 350 consecutive
      patients of more than five years of age with clinical diagnosis of otomycosis
      were included in the study. Demographic profile, predisposing factors, presenting
      complaints and clinical findings of clinically diagnosed patients were evaluated
      and analyzed. Samples were collected, transported and evaluated by both direct
      examination and culture method for bacteriological and mycological examination.
      RESULTS: Male to female ratio in study participants was 1.3:1. Mycological
      examination yielded 346 fungal isolates in 310 samples from a total of 350
      clinically diagnosed cases of otomycosis. Self cleaning, instillation of mustard
      oil and use of ear drops appeared to be common predisposing factors in
      otomycosis. Significant association was observed between these practices and
      otomycosis. Aspergillus species was the predominant fungi followed by Candida
      spp., Penicillium, Mucor and Trichophyton mentagrophyte. 11% of the cases were
      found to have mixed fungal and bacterial infections. CONCLUSION: The present
      study highlights the highest isolation of Aspergillus complex in cases of
      clinically diagnosed otomycosis in a rural community with higher practice of self
      cleaning and using home remedies and eardrops to get relief from sensation of
      blocked ear and itching.

PMID- 28764160
TI  - Revisiting Nitrofurantoin for Vancomycin Resistant Enterococci.
AB  - INTRODUCTION: Enterococcal infection has emerged as a major therapeutic
      challenge. Emergence of High Level Aminoglycoside Resistance (HLAR) and
      Vancomycin-Resistant Enterococcus (VRE) has further limited the drug therapy in
      enterococcal infections. However, nitrofuratoin being an old drug reported to
      have less resistance in comparison to the other classes of antimicrobial agents.
      AIM: To detect susceptibility of nitrofurantoin against VRE isolates from Urinary
      Tract Infection (UTI) of outdoor and indoor patient departments. MATERIALS AND
      METHODS: An observational study was carried out at a tertiary care hospital in
      New Delhi over a period of six months (from November 2015 to April 2016). A total
      of 14,714 urine samples were collected and processed from the patients
      symptomatic for UTI. The enterococcal isolates were identified and confirmed by
      standard phenotypic tests. The antimicrobial susceptibility tests of isolated
      organisms were performed by Kirby-Bauer Disc Diffusion Method as per Clinical and
      Laboratory Standards Institute (CLSI) 2015 guidelines. The Wilcoxon rank-sum
      (Mann-Whitney) test was used to compare continuous variables. Chi-square or
      Fisher's exact tests were used to compare categorical variables. p<0.05 was
      considered as significant. RESULTS: A total of 70 enterococci species
      {Enterococcus faecalis (n=9), Enterococcus faecium, (n=61)} were isolated. Twenty
      six out of 70 isolates were observed resistant to vancomycin. Among 26 VRE,
      21(80.76%) were susceptible to nitrofurantoin. Both the species {E. faecalis
      (80.32%) and E. faecium (88.8%)} were uniformly susceptible to nitrofurantoin.
      CONCLUSION: Nitrofurantoin has retained antimicrobial efficacy against emerging
      VRE in vitro and can be used for treatment of enterococcal urinary tract
      infections.

PMID- 28764161
TI  - Providencia Rettgeri: An Emerging Nosocomial Uropathogen in an Indwelling Urinary
      Catheterised Patient.
AB  - Providencia rettgeri (P. rettgeri) is an ubiquitous organism but is seldom
      associated with human disease. We report the isolation of P. rettgeri from the
      urine sample of a 39-year-old male patient on prolonged Foley's catheterisation
      following a severe head injury. Identification of this organism was done by
      Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry
      (MALDI-TOF) based systems. P. rettgeri is an emerging pathogen among long term
      catheterised patients. It reflects its ability to form biofilm on the surface of
      the indwelling catheter as well as the inherent urease producing property of the
      pathogen in question as a possible mechanism of pathogenesis.

PMID- 28764162
TI  - Taeniasis: An Unusual Presentation.
AB  - We report a case of 45-year-old male presenting with the history of nasal
      expulsion of segments of Taenia saginata. This route of expulsion is a rare
      occurrence. The report stresses this unusual presentation of taeniasis in endemic
      region.

PMID- 28764163
TI  - Native Valve Endocarditis Caused by Escherichia Coli.
AB  - Escherichia coli is a rare cause of infective endocarditis. This report describes
      a case of native valve endocarditis caused by Escherichia coli in a 58-year-old
      male renal transplant patient who had a concurrent urinary tract infection caused
      by the same organism. The patient was successfully treated with antibiotics and
      recovered without surgical intervention.

PMID- 28764164
TI  - Chryseobacterium Indologenes Pneumonitis in an Infant: A Case Report.
AB  - Chryseobacterium indologenes, a non-fermentative Gram-negative bacilli
      distributed widely in nature, is an emerging nosocomial pathogen, inherently
      resistant to a wide range of antibiotics. There is limited number of C.
      indologenes infections reported from India. We report a case of C. indologenes
      associated pneumonia in a three-month-old infant with congenital heart disease.
      This case highlights the importance of prompt diagnostic workup and targeted
      antibiotic therapy for its effective management.

PMID- 28764165
TI  - Ocular Dirofilariasis: A Rare case from Mumbai, India.
AB  - Dirofilariasis is a worldwide zoonotic filariasis. Human dirofilariasis is a
      zoonotic infection most commonly caused by Dirofilariarepens. Dirofilariasis,
      caused by Dirofilaria repens, has been reported to occur widely throughout Asia,
      Europe, and Africa. It has not been widely recognized in India; however, several
      cases have been reported in the last few years. Ease and frequency of
      international travel has probably contributed to the increase in the number of
      cases. There is probably a focus of human infection with D. repens in Kerala,
      India. We report a case of ocular dirofilariasis, from the Western part of India.
      Among the Indian case reports of human dirofilariasis caused by D. repens,
      majority had ocular infections and few had subcutaneous involvement of the face.

PMID- 28764166
TI  - Phytotherapy in Streptococcusagalactiae: An Overview of the Medicinal Plants
      Effective against Streptococcus agalactiae.
AB  - Streptococcus agalactiae is a spherical and Gram-positive bacterium that causes
      postpartum sepsis, endometritis, chorioamnionitis and premature delivery in
      pregnant women. The use of herbs and natural ingredients for the treatment of
      various disorders has been common. The present review is a report on the
      medicinal plants with anti-Streptococcus agalactiae effects. In this review, the
      search was carried out in Web of Science, PubMed, Scopus, Google Scholar and
      Science direct by keywords such as bacteria, Streptococcus agalactiae and
      medicinal plants. According to the search results, 10 medicinal plants are used
      as anti-bacterial against Streptococcus agalactiae. Results of this study suggest
      that the active ingredients listed in this review paper used for pharmacological
      studies on Streptococcus agalactiae so it can produce effective natural
      antibiotic for the future.

PMID- 28764167
TI  - Comment on "Serological Evidence of Scrub Typhus among Cases of PUO in the
      Kashmir Valley- A Hospital Based Study".

PMID- 28764169
TI  - Histomorphological Spectrum of Duodenal Pathology in Functional Dyspepsia
      Patients.
AB  - INTRODUCTION: Functional Dyspepsia (FD) is one of the most common causes of
      gastrointestinal symptoms aetiology of which is poorly understood. AIM: To study
      duodenal histomorphological features and their relationship with Helicobacter
      pylori (H Pylori) infection in patients of FD. MATERIALS AND METHODS: This case
      control study included 50 cases of FD patients selected according to Rome III
      criteria and 30 age and sex matched controls. These were subjected to oesophago
      gastro-duodenoscopy, rapid urease test for detection of H. pylori on gastric
      antral biopsy and duodenal biopsy from second part of duodenum for
      histopathological evaluation by light microscopy. Ten antral urease positive
      cases of FD with highest Intraepithelial Lymphocyte Count (IEL) were subjected to
      Immunohistochemistry (IHC). RESULTS: Duodenal inflammation was an invariable
      feature noted in FD. Morphological spectrum consisted of increased IEL in 72%,
      increased duodenal eosinophils in 92%, presence of focal villous atrophy in 16%,
      lymphoid aggregates, colonic metaplasia, and duodenal H. pylori infection in 4%
      each. Gastric H. pylori positivity was noted in 48% cases of FD. Increased
      duodenal IEL count and duodenal eosinophilia was noted in 75%, 87.5% such cases.
      Same was noted respectively, with 61.5% and 95.15% cases with gastric H. pylori
      negativity. In cases of FD, duodenal IEL and eosinophil count in lamina propria
      showed statistically significant rise when compared with control and had positive
      correlation with gastric H pylori infection. On IHC, increased expression of CD 8
      was noted in duodenal IEL and lymphocytes in lamina propria as compared to CD4.
      CONCLUSION: Our study provided some insight in pathogenesis of FD and role of H.
      pylori in its aetiology.

PMID- 28764168
TI  - Drug Resistance Pattern in the Recent Isolates of Salmonella Typhi with Special
      Reference to Cephalosporins and Azithromycin in the Gangetic Plain.
AB  - INTRODUCTION: Typhoid fever is an endemic disease in India against which many
      antibiotics are available. In the recent times, emerging resistance to
      traditional antibiotics, such as Ampicillin, Chloramphenicol and
      Trimethoprim/sulfamethoxazole, Azithro-mycin and third generation Cephalosporins
      are being reported and increasingly being used in the treatment of invasive
      Salmonella infections. However, the latter two drugs have been reported with
      occasional clinical failures. Currently, we do not have data regarding their drug
      resistance levels in the recent isolates of Salmonella enterica subspecies
      enterica serotype Typhi. AIM: To determine the current levels of drug resistance
      of the two drugs (i.e., cephalosporins and azithromycin) against S. Typhi
      isolates. MATERIALS AND METHODS: It is a prospective case study. A total of 47
      recent strains of S. Typhi were isolated from blood and stool specimens. These
      isolates were subjected to identification and confirmation by biochemical,
      serological tests followed by genotypic methods. The antimicrobial testing was
      done by disc diffusion and Minimum Inhibitory Concentration (MIC) methods for
      various in use antibiotics including ceftriaxone and azithromycin from February
      2011 to March 2013 in the Department of Microbiology, Institute of Medical
      Sciences, Banaras Hindu University, Varanasi, India. RESULTS: It was intriguing
      to see the return of conventional drugs such as chloramphenicol, amoxicillin and
      co-trimoxazole. The drugs like quinolones, ceftriaxone and azithromycin were
      found to be ineffective against >20% of the isolates. However, nalidixic acid was
      found to have maximum resistance (36/47,76.6%) while highest sensitivity was
      observed for chloramphenicol (1/47,2.1%). Moreover, co-trimoxazole (9/47,19.1%)
      has displayed with significant come back. CONCLUSION: It could be concluded that
      combination of amoxicillin and co-trimoxazole would prove as good as azithromycin
      or ceftriaxone alone for empirical therapy of S. Typhi infection. However,
      detection of an isolate (1/47, 2.1%), sensitive only to chloramphenicol, a drug
      known for causing bone marrow suppression, is an alarming sign.

PMID- 28764170
TI  - Histopathological Analysis of Brain Tumours- A Seven Year Study from a Tertiary
      Care Centre in South India.
AB  - INTRODUCTION: Tumours of central nervous system constitute 1%-2% of tumours in
      adults. The incidence of brain tumours has been reported to be around 3.9 and
      3.0/one lac/year in males and females respectively. A few studies are available
      from India which show a lower incidence of brain tumours compared to the
      developed countries. Not much is known about the epidemiology of brain tumours in
      the population from South India. AIM: To identify the age groups, gender
      distribution, topography and different histological types of brain tumours.
      MATERIALS AND METHODS: A total of 510 cases of brain tumours were identified over
      a period of seven years which were included in the present study. We retrieved
      the slides of these cases and reviewed them. Immunohistochemistry in required
      cases were done. Age and gender distribution, clinical presentation, site of
      tumour and histopathologic patterns with grade were noted and the data was
      analysed with SPSS software version 17.0. RESULTS: Our analysis showed that most
      of the brain tumours occur between 40-60 years of age, with a male to female
      ratio of 0.9:1. Majority of cases involved dura and cerebral lobes except for the
      occipital lobe, and meningioma and glial tumours were the most common broad
      histological types. WHO grade IV tumours and metastasis were common in males
      compared to females. CONCLUSION: This study revealed the distribution of brain
      tumours in patients attending our institution. The results obtained were
      comparable with available worldwide data.

PMID- 28764172
TI  - Clinico-Haematological Profile of Hereditary Haemolytic Anaemias in a Tertiary
      Health Care Hospital in South India.
AB  - INTRODUCTION: Hereditary haemolytic anaemia is a common inherited disorder
      causing varying degree of morbidity and mortality. This includes disorders due to
      haemoglobin defect, membrane defect, and enzyme defect. Among them
      haemoglobinopathies, a single gene disorder, constitutes the major part of the
      disorder and is distributed worldwide with an incidence of 5%. These inherited
      disorders pose a major public health problem and increase the burden both on the
      patient and the society. Presently, these disorders are not curable but can only
      be prevented. Improved awareness about these diseases among medical fraternity
      leading to diagnosis of carrier state, genetic counselling, and antenatal
      diagnosis may help in decreasing the prevalence of the disease. AIM: To determine
      the prevalence of hereditary haemolytic anaemia and to correlate clinical and
      haematological features. MATERIALS AND METHODS: The study was carried for
      duration five and half years (four years of retrospective and one and a half
      years prospective). All the patients diagnosed as hereditary haemolytic anaemia
      based on peripheral smear and special haematological investigation were included
      in the study. The clinical parameters and haematological parameters of all these
      patients were studied. RESULTS: A total of 322 cases of hereditary haemolytic
      anaemia were diagnosed over a period of five and a half years. Of them
      thalassaemia syndrome constituted 165 cases (51.24%), sickle cell disorders 78
      cases (24%), hereditary spherocytosis 43 cases (13.3%), G6PD deficiency 20 cases
      (6.29%) and HbE disorder 12 cases (3.7%). One case of hereditary elliptocytosis
      and one case of HbD Punjab was detected. Among thalassaemia syndromes beta
      thalassaemia was commonest clinically presenting disorder with a high morbidity.
      Sickle cell anaemia showed a higher level of HbF and a relatively milder clinical
      course. Hereditary spherocytosis had varied age at presentation. In G6PD
      deficiency drug induced haemolysis was the commonest clinical presentation. HbE
      disorders were from the north eastern states. CONCLUSION: Haemoglobinopathies
      constitute the major group of hereditary haemolytic anaemia (74%). Genetic
      counselling is an important step in reducing the incidence of thalassaemia major.

PMID- 28764171
TI  - Evaluation of Hypoxia Inducible Factor-1alpha and Glucose Transporter-1
      Expression in Non Melanoma Skin Cancer: An Immunohistochemical Study.
AB  - INTRODUCTION: Hypoxia Inducible Factor-1 (HIF-1) is a mediator enabling cell
      adaptation to hypoxia. It plays its role mainly through transcription of many
      target genes including Glucose Transporter-1 (GLUT-1) gene. AIM: The present work
      aimed at evaluating the pattern and distribution of HIF-1alpha and GLUT-1 in each
      case and control. MATERIALS AND METHODS: A case-control and retrospective study
      was conducted on archival blocks diagnosed from pathology department as, Basal
      Cell Carcinoma (BCC, 20 cases), cutaneous Squamous Cell Carcinoma (SCC, 20 cases)
      and 20 normal site-matched skin biopsies from age and gender-matched healthy
      subjects as a control. Evaluation of both HIF-1alpha and GLUT1 expression using
      standard immunohistochemical techniques was performed on cut sections from
      selected paraffin embedded blocks. RESULTS: HIF-1alpha was expressed in 90%, 35%
      and 100% of normal skin, BCC and SCC tumour islands respectively. It was up
      regulated in both BCC and SCC compared with normal skin (p= 0.001, p<0.001
      respectively). GLUT-1 was expressed in 100%, 70% and 100% of normal skin, BCC and
      SCC tumour islands respectively. It was down regulated in Non Melanoma Skin
      Cancer (NMSC) cases compared with normal skin (p=0.004). HIF-1alpha and GLUT-1
      localization in tumour nests was central, peripheral or central and peripheral.
      Both HIF-1alpha and GLUT-1 showed variable expression in stroma, adnexa and
      inflammatory cells. No significant correlation was found between Histo (H) score
      or expression percentage values of HIF-1alpha and those of GLUT-1 in tumour
      islands or in overlying epidermis either in BCC or SCC. CONCLUSION: HIF-1alpha
      may have a role in NMSC pathogenesis through adaptation to hypoxia which results
      from excessive proliferation. GLUT-1 down regulation in NMSC may be explained by
      its consumption by proliferating tumour cells. The expression of HIF-1alpha and
      GLUT-1 in normal epidermis, stromal and adnexal structures needs further
      research.

PMID- 28764173
TI  - Clinical and Laboratory Predictors of Frequency of Painful Crises among Sickle
      Cell Anaemia Patients in Nigeria.
AB  - INTRODUCTION: The severity of Sickle Cell Anaemia (SCA) in terms of frequency of
      painful Vaso-Occlusive Crises (VOC) may be affected by clinical and
      haematological parameters amongst others. Elucidation of these factors in a given
      disease prevalent environment is necessary for prompt and effective management of
      patients with frequent painful VOC. AIM: This study aimed at determining the
      clinical and laboratory predictors of frequency of painful VOC among SCA patients
      in Enugu, Southeastern Nigeria. MATERIALS AND METHODS: It was a cross-sectional
      study of 100 consecutive SCA patients receiving care at the University of Nigeria
      Teaching Hospital, Enugu, Nigeria between May 2012 and February 2014. The
      eligible patients were categorized into two groups namely; Group A and Group B.
      Group A/study group (severe disease) comprised SCA patients who had experienced
      three or more painful crises (>=3 crises) in the last one year preceding the
      study but, currently in steady state, while Group B/control group (mild-moderate
      disease), comprised SCA patients matched for age, sex, highest educational
      status, and occupation but who have had no painful crisis or had only one or two
      painful crises (0-2 crises) in the last one year preceding the study and
      currently in steady state. RESULTS: The overall mean age of the patients was
      18.4+/-12.2 (range=2-52) years. The mean values of the haematological parameters
      including haemoglobin concentration, white cell count, platelet count, and
      neutrophil count were significantly higher in those with severe crises than mild
      moderate crises (p<0.05). Sickle cell related complications including Avascular
      Necrosis (AVN) and leg ulcers were significantly higher in the study group than
      the control group (p<0.05). CONCLUSION: There was significant association between
      the frequency of crises and haemogblobin level, platelet and neutrophil counts
      and some clinical parameters: AVN, nephropathy and stroke. Future preventive
      interventions for reduction in frequency of crisis amongst patients with SCA
      could be targeted at controlling the blood levels of the identified
      haematological parameters.

PMID- 28764174
TI  - An Indian Tertiary Care Hospital Scenario of Papillary Carcinoma of Thyroid.
AB  - INTRODUCTION: Thyroid carcinoma is the most common endocrine malignancy and its
      Papillary Histotype {Papillary Carcinoma of Thyroid (PTC)} is the most common
      type of Thyroid cancer. The clinicopathological features of PTC vary with
      geographical location. AIM: To describe the clinicopathological profile of PTC in
      a Tertiary Care Hospital located in Chennai, Tamil Nadu, India. MATERIALS AND
      METHODS: Data on age, sex, centricity of the tumour, presence of calcifications,
      infiltration, metastasis, associated non malignant conditions and frequency of
      histological subtypes of all cases of PTC diagnosed in Department of Pathology,
      Madras Medical College Chennai, Tamil Nadu, India between January 2007 and
      December 2011 were obtained from clinicopathological documents and analysed
      statistically. RESULTS: Statistically significant correlations were found between
      age and sex, age and metastasis, sex and centricity, sex and metastasis, size of
      lesion and sex, size of lesion and age, size and presence of calcifications and
      presence of calcifications and metastasis. CONCLUSION: Scenario of PTC in our
      tertiary care setup which warrants attention is male preponderance of
      multicentric lesions. Further, a high association with colloid nodular goitre,
      while low incidence of tall cell variant is notable clinico pathological
      scenarios in this study.

PMID- 28764175
TI  - Aggressive Angiomyxoma in Males.
AB  - Paratesticular aggressive angiomyxoma is a very rare tumour in males. Most of
      documented cases of aggressive angiomyxomas have been seen in genital, perineal
      and pelvic regions in women of child bearing age. We report two cases of
      aggressive angiomyxomas in males who presented with inguinal swellings. A
      globular mass with greyish white, glistening cut surface was received after
      excision of the mass. Microscopic examination revealed a paucicellular tumour
      comprising of spindle shaped cells along with vessels of varying calibre. The
      accompanying stroma was myxocollagenous. In addition there was evidence of fat
      infiltration in one of the cases. Immunohistochemical staining showed CD34,
      desmin, vimetin positivity and negative staining for S100, actin, Estrogen
      Receptors (ER) and Progesterone Receptors (PR). The microscopic and
      immunohistochemical features favoured the diagnosis of aggressive angiomyxoma.
      This report of angiomyxoma in two cases of males assumes great significance in
      view of the extreme rarity of the tumour in males and its locally infiltrative
      nature.

PMID- 28764176
TI  - Infiltrating Ductal Carcinoma Co-Existing with Intraductal Papillary Carcinoma of
      Male Breast: A Rare Case Report.
AB  - Male breast carcinomas are rare tumours, accounting for less than 1% of all
      malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very
      rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the
      classical clinical, radiological and cytological features of malignancy and
      usually presents as a benign-appearing lump. We report a case of Infiltrating
      Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53
      year-old male who presented with lump in the right breast.

PMID- 28764177
TI  - Idiopathic Tumoral Calcinosis - Rare Clinico Pathological Entity: A Report of Two
      Cases.
AB  - Tumoral calcinosis is a rare disease reported mainly in blacks of tropical and
      subtropical African regions. It is characterized by tumour-like periarticular
      deposits of calcium that are found in the regions of the hip, shoulder, elbow and
      small joints of hands and feet. The involvement of this disease in a healthy
      patient is extremely rare in young and middle aged individuals. We are presenting
      two cases with large, painless periarticular swellings in subscapular joint and
      feet. First case presented with recurrent swelling in different anatomical
      locations at different time intervals involving the hip and followed by shoulder
      joint. Second case presented with swelling around the ankle joint. These two
      cases were diagnosed as Idiopathic tumoral calcinosis based on biochemical,
      radiological and histopathological findings.

PMID- 28764178
TI  - Aneurysmal Variant of Fibrous Histiocytoma- A Rare Entity Known for Recurrence.
AB  - Aneurysmal Fibrous Histiocytoma (AFH) is a distinct and a rare
      clinicopathological variant of Cutaneous Fibrous Histiocytoma (CFH). It differs
      from the usual benign fibrous histiocytoma clinically and morphologically with
      high rate of recurrence. Here, we report a case of AFH with history of recurrence
      which presented as a polypoid swelling and showed vascular spaces with no
      endothelial lining which was proved negative by CD34 immunostaining. The spaces
      were bordered by tumour cells.

PMID- 28764179
TI  - Bilateral Giant Juvenile Fibroadenoma of Breast.
AB  - Fibroadenomas are benign lesions of breast commonly found in young age group.
      These focal tumours contain both mesenchymal and glandular tissue. Giant juvenile
      fibroma of breast is rare variant of fibroadenoma found usually in less than 20
      years of age. They present with rapid enlargement of single or multiple,
      discrete, painless large nodule of breast. A 14-years-old premenarche girl
      presented with large bilateral breast lumps for two months. FNAC showed features
      of juvenile fibroadenoma. Breast conserving surgical excision of lumps was
      performed and histopathology confirmed the diagnosis of juvenile fibroadenoma.
      Giant juvenile fibroadenomas are characterised by rapid enlargement of
      encapsulated mass. The aetiology is unknown, although end-organ hypersensitivity
      to normal level of estrogen is postulated. We present a case of bilateral giant
      juvenile fibroadenoma for its rarity.

PMID- 28764180
TI  - High Grade Serous Cystadenocarcinoma of Testis-Case Report of a Rare Ovarian
      Epithelial Type Tumour.
AB  - Ovarian epithelial type tumour of testis are extremely rare tumours that resemble
      ovarian surface epithelial tumours. They usually present as testicular or
      paratesticular tumours and can be serous, mucinous, endometrioid or Brenner
      tumour. Serous and mucinous types account for the majority of tumours. The
      tumours are benign, borderline or malignant, commonly borderline. Here, we report
      a case of high grade serous cyst adenocarcinoma of testis which manifested as
      extensive metastasis in supraclavicular, mediastinal and abdominopelvic groups of
      lymph nodes, lung and adrenal gland without clinical evidence of an overt primary
      tumour. We report this case so as to make clinicians and pathologists aware of
      this rare entity and to stress on the fact that this rare entity should be kept
      in mind when evaluating cases of metastatic adenocarcinoma in male patients.

PMID- 28764181
TI  - Invasive Cystic Hypersecretory Carcinoma of Breast: A Rare and Under Diagnosed
      Variant of Ductal Carcinoma.
AB  - Handful cases of invasive Cystic Hypersecretory Ductal Carcinoma (CHC) have been
      reported so far in literature. Cystic hypersecretory lesions of breast have a
      spectrum of morphological features ranging from Cystic Hypersecretory Hyperplasia
      (CHH), CHH with atypia, in situ to invasive CHC. We are reporting a case of a 32
      year-old female who had nipple discharge and lump in her right breast for one
      month. A modified radical mastectomy was done and morphological diagnosis of
      invasive CHC with axillary node metastasis was made. The postoperative events
      were uneventful. Invasive CHC being a rare entity, our understanding of its
      biological behavior, prognostic factors and genetic basis is limited. The authors
      are aware of only 15 similar cases being reported in the English literature.

PMID- 28764182
TI  - Pigmented Villonodular Synovitis of Thumb-A Cytological Diagnosis.
AB  - Pigmented Villonodular Synovitis (PVNS) is a unique benign proliferative process
      of unknown aetiology involving the synovial lined joints diffusely or focally.
      The entity remains a diagnostic challenge. This condition is attributed to an
      increased synovial proliferation causing villous or nodular changes of synovial
      lined joints leading to PVNS, Pigmented Villonodular Bursitis (PVNB) when arising
      from bursae or Pigmented Villonodular Tenosynovitis (PVNTS) originating from the
      tendon sheath. We present a case of a young female with nodular masses on right
      thumb with cytomorphological features on FNAC suggestive of PVNS which was
      finally confirmed by histopathology.

PMID- 28764183
TI  - Acquired Inhibitor of Factor VIII Presenting as Delayed Wound Healing.
AB  - Acquired coagulation factor VIII inhibitor leads to a rare disease i.e., acquired
      haemophilia which is idiopathic in majority of cases and is seen with autoimmune
      diseases, haematologic and solid tumours, infections, in the post-partum period
      and also with certain long-term use of drugs like penicillin and its derivatives,
      phenytoin, sulfa antibiotics, chloramphenicol, methyldopa, chlorpromazine,
      levodopa, interferon-alpha, fludarabine, clopidogrel. We report a case here, with
      acquired Factor VIII (FVIII) inhibitor acquisition which presented with delayed
      wound healing as a result of protracted bleeding into the wound. The inhibitor
      was acquired due to prolonged chlorpromazine use.

PMID- 28764184
TI  - Ichthyosis Uteri Associated with Endometrial Adenocarcinoma: A Case Report.
AB  - The replacement of the entire or extensive parts of endometrial lining by
      stratified squamous epithelium is a rare entity known as ichthyosis uteri. It is
      considered to be a benign condition but may be associated with dysplastic changes
      and primary squamous cell carcinoma of the endometrium. Its association with
      endometrial adenocarcinoma is very rare. The aetiology of this condition is not
      clearly understood till date. We report a case of ichthyosis uteri associated
      with endometrial adenocarcinoma in a 70-year-old female who presented with
      complaint of per-vaginal bleeding for six months and underwent hysterectomy after
      being diagnosed with endometrial carcinoma. Microscopic examination of sections
      revealed endometrioid adenocarcinoma International Federation of Gynaecology and
      Obstetrics (FIGO) Grade 3 along with extensive replacement of the endometrial
      lining by stratified squamous epithelium, consistent with ichthyosis uteri.
      Although ichthyosis uteri is considered benign and its malignant potential is yet
      to be established, its association with endometrial malignancies, both squamous
      and adenocarcinoma, necessitates extensive sampling of the uterus if any focus of
      squamous metaplasia is identified in a hysterectomy specimen, to rule out a co
      existing carcinoma.

PMID- 28764185
TI  - Kikuchi-Fujimoto Disease Masquerading as Acute Appendicitis.
AB  - Kikuchi-Fujimoto Disease (KFD) is a self-limiting necrotizing lymphadenitis that
      usually presents with fever and cervical lymphadenopathy. Recognition of this
      condition is crucial, because it can be mistaken for tuberculosis, lymphoma and
      connective tissue disorders. When present at an unusual location the diagnosis
      can be challenging. We present an unusual case of Kikuchi-Fujimoto disease
      involving mesenteric lymph node masquerading as acute appendicitis along with its
      differential diagnosis. A 30-year-old female presented with complaints of acute
      abdominal pain, vomiting and fever. Physical examination revealed rebound
      tenderness in the right iliac fossa. The abdominal sonography was suspicious of
      acute appendicitis. The patient underwent appendectomy with excision of an
      enlarged mesenteric lymph node. On histopathology mesenteric node showed features
      of KFD which was confirmed on immunohistochemistry. Appendix was unremarkable.
      Although rare KFD should be added to the differential diagnosis of acute
      appendicitis in patients with enlarged mesenteric lymph nodes, Awareness of this
      disorder helps to prevent misdiagnosis and inappropriate treatment.

PMID- 28764186
TI  - Intraosseous Epidermal Inclusion Cyst of the Great Toe: Masquerading as Bone
      Tumour.

PMID- 28764187
TI  - Visceral Leishmaniasis in an Immunocompromised Patient: Diagnostic Bone Marrow
      Cytomorphology.

PMID- 28764188
TI  - Cytology of Collagenous Spherulosis: A Case Series.
AB  - Collagenous Spherulosis (CS) is an uncommon benign entity characterized by the
      presence of pink hyaline globules composed of basement membrane like material.
      Although they are known to occur independently, they are more often found as
      incidental findings in association with benign pro iferative breast lesions. As
      morphologically similar hyaline globules also occur in certain malignant lesions
      such as Adenoid Cystic Carcinoma (ACC) and adenomyoepithelial carcinoma, their
      presence may pose diagnostic problems. The present series is a retrospective
      analysis of six cases of CS reported cytologically over a period of three years
      from 2013 to 2016 at Chettinad Hospital and Research, Tamil Nadu, India. The
      cytopathologist should be aware of this benign entity to distinguish it from
      similar looking malignant lesions to avoid inappropriate management.

PMID- 28764189
TI  - Comparison of Efficacy and Safety of Cefpodoxime and Amoxicillin-Clavulanate
      Potassium in Paediatric Acute Otitis Media in Children below Two Years: A
      Prospective Longitudinal Study.
AB  - INTRODUCTION: Acute Otitis Media (AOM) is one of the frequently diagnosed
      diseases in children below two years. Amoxicillin-clavulanate potassium is the
      first line drug in treatment of Paediatric AOM (PAOM). Cefpodoxime has good
      antimicrobial activity against various types of microorganisms that include
      causative microorganisms of PAOM. AIM: To compare the efficacy and safety of
      cefpodoxime and amoxicillin-clavulanate potassium for the treatment of PAOM in
      children below two years. MATERIALS AND METHODS: A prospective longitudinal study
      was conducted on children diagnosed with PAOM. Thirty-six children were included
      in the study: 17 in the Group A (amoxicillin-clavulanate potassium) and 19 in the
      Group B (cefpodoxime). Primary outcome of this study was clinical success rate at
      day 10 visit and secondary outcome was incidence of Adverse Events (AEs).
      RESULTS: The clinical success rates were 93.8% in Group A and 88.2 % in Group B.
      These rates are comparable and no statistically significant difference was
      observed between the groups. Few mild and self-limiting AEs were observed and
      both the drugs were well tolerated. CONCLUSION: The results of this prospective
      study showed that a 10-day course of cefpodoxime is therapeutically comparable to
      amoxicillin-clavulanate potassium in terms of both efficacy and safety for the
      treatment of PAOM in children below two years.

PMID- 28764190
TI  - Comparison of Plasma Levels of Renin, Vasopressin and Atrial Natriuretic Peptide
      in Hypertensive Amlodipine Induced Pedal Oedema, Non-Oedema and Cilnidipine
      Treated Patients.
AB  - INTRODUCTION: Amlodipine is a third generation dihydropyridine group of calcium
      channel blocker and having an excellent antihypertensive profile. Pedal Oedema
      (PE) is the major drawback of amlodipine therapy and the incidence of Amlodipine
      Induced Pedal Oedema (AIPE) has been found significantly high. Several
      neurohumoral factors influence the incidence of oedema. AIM: We aimed to compare
      the plasma levels of renin, vasopressin and atrial natriuretic peptide in
      hypertensive AIPE, non-oedema and cilnidipine treated patients. MATERIALS AND
      METHODS: The present prospective, interventional study was conducted on 104 mild
      to moderate hypertensive patients (52 patients in each group), after due
      consideration of eligibility criteria. Plasma Renin (PR), Vasopressin (VAS), and
      the Atrial Natriuretic Peptide (ANP) was estimated by ELISA test and compared
      between the AIPE, Amlodipine Treated Non-Oedema (ATNE) in Phase I, and AIPE and
      Cilnidipine Treated (CT) Groups in Phase II. RESULTS: The clinical and
      demographic parameters were matched. PR was significantly high in AIPE group than
      the ATNE, and it was significantly reduced after one month follow up with the
      substitution of cilnidipine. The median (IQR) value of PR was 4.87 (3.58, 6.63),
      3.50 (1.44, 5.47) and 2.66 (1.02, 5.66) ng/ml in AIPE, ATNE, CT group
      respectively. VAS was significantly high in AIPE group than ATNE, and it
      significantly reduced after one month follow up with CT group. The median (IQR)
      value of vasopressin was 6.78 (2.55, 9.16), 2.58 (1.61, 5.73) and 2.50 (1.23,
      5.00) ng/ml in AIPE, ATNE and CT groups respectively. There was no significant
      difference seen in plasma ANP levels between the groups. The p-value was <0.05
      which is statistically significant. CONCLUSION: The AIPE may not be volume
      overload or fluid retention; it may be due to persistent raise in adrenergic
      activity followed chronic amlodipine therapy. Cilnidipine relatively suppresses
      the sympathetic activity, and completely resolves the AIPE by significantly
      reducing PR and VAS levels. ANP did not show a difference between groups.
      Cilnidipine is the suitable alternative antihypertensive drug for AIPE patients.

PMID- 28764191
TI  - Knowledge and Perception about Pharmacovigilance among Pharmacy Students of
      Universities in Sana'a Yemen.
AB  - INTRODUCTION: Pharmacists in community or hospital setting play a key role in
      reporting Adverse Drug Reaction (ADRs) during practice. Under reporting is
      considered as a profession malpractice worldwide. AIM: To determine the level of
      knowledge and perception about phramacovigilance and ADRs reporting among final
      year pharmacy students of Universities in Sana'a Yemen. MATERIALS AND METHODS: A
      cross-sectional study design was conducted among 385 final year pharmacy
      students. One public and four private universities were selected randomly using a
      validated self-administered questionnaire. The questionnaire contained data about
      student demographic data, knowledge and perception about the ADRs. The data was
      analysed by SPSS program and Chi-square tests were used to assess the
      significance of association. RESULTS: The male students were more knowledgeable
      than female (p=0.035), as well as private university students had better ideas on
      how to report ADRs than public university students (p=0.009). Private university
      students reported that pharmacovigilance topic is well covered in their
      curriculum compared to public university students (p<=0.001). A significant
      difference was seen amongst the students of public and private universities when
      asked about reporting ADRs in future, former found more confident (p<=0.001).
      Furthermore, the private university students also had more command on the concept
      of post-marketing surveillance than public university students (p<=0.001). The
      private university students in Yemen were more known to causality assessment of
      ADRs as compared to the students of public universities (p<=0.001). The results
      of perception revealed regarding perception toward ADRs and pharmacovigilance.
      Female students (p<=0.018) and private universities students (p<=0.001) had
      positive perception than male and public university students respectively.
      CONCLUSION: The findings showed poor knowledge among students in Sana'a
      Universities and positive perception towards pharmacovigilance and ADRs
      reporting. A poor knowledge among the future pharmacists suggests need for
      educational interventions and improvement of strategies to ease the reporting
      mechanisms. Steps can be taken to improve pharmacovigilance tools and methods in
      Yemen as well as incorporating subjects of pharmacovigilance in the health
      faculty's curriculum in Yemen.

PMID- 28764192
TI  - Evaluation of Antiulcer Activity of Peltophorum Pterocarpum.
AB  - INTRODUCTION: Peltophorum pterocarpum is a rich source for phenols and the wood,
      leaves, and flowers of the plant are used as medicinal agents in traditional
      medicine. Peptic ulcer is a major disease of gastrointestinal tract, affecting
      nearly 40 lac people each year worldwide and affects 10% of world population with
      different aetiologies. Peltophorum pterocarpum consists of phenols and
      flavonoids, tannins which have potential antioxidant and cytoprotective activity.
      AIM: To evaluate the antiulcer activity of methanolic extract of the leaves of
      Peltophorum pterocarpum (MEPP) on albino rats. MATERIALS AND METHODS: The rats
      were divided into four groups as control, standard, test 1 (extract: 100 mg/kg)
      and test 2 (extract: 200 mg/kg) with six rats in each group. Gastric lesions were
      induced by oral administration of indomethacin (20 mg/kg) followed by pylorus
      ligation. Standard group of animals were treated with misoprostol and test group
      of animals were treated with MEPP at doses of 100 and 200 mg/kg. To determine the
      antiulcer activity of extract, mean ulcer index, free acidity and total acidity
      were evaluated. RESULTS: Ulcer index was significantly decreased at p<0.01 in
      MEPP treated groups as compared to control group. Total and free acidity was
      significantly decreased at p<0.01 in MEPP treated groups as compared to control
      group. Histological analysis also supported the gastro protective effect of MEPP
      treated groups when compared with control groups. CONCLUSION: The study revealed
      that MEPP exhibited potential antiulcer activity and showed dose dependent
      antiulcer effect.

PMID- 28764193
TI  - Effect of Ethyl Acetate Extract of Melothria Perpusilla on Oral Glucose Tolerance
      Test in Albino Rats.
AB  - INTRODUCTION: Diabetes mellitus is a group of common metabolic disorders sharing
      the phenotype of hyperglycaemia. Certain disadvantages like side effects or less
      efficacy limit the optimal use of antidiabetic drugs. AIM: To evaluate the effect
      of Ethyl Acetate Extract of MelothriaPerpusilla (EAEMP) on oral glucose tolerance
      test in albino rats. MATERIALS AND METHODS: Six healthy albino rats weighing
      between 100-150 g were selected. The same set of six animals were used for the
      experiment throughout and successive tests were conducted after a drug wash out
      period of 10 days. Fasting blood glucose samples were measured using glucometer.
      A 2% gum acacia suspension {10 ml/kg per oral (p.o.)} was given in all six albino
      rats followed by the oral glucose load of 3g/kg. Glucose concentrations were
      estimated at one hour and two hour after the glucose load. Using the same set of
      animals, similar tests were repeated with the test dose of 250 mg/kg and 500
      mg/kg of EAEMP and glibenclamide (0.5 mg/kg p.o.). In this experiment, glucose
      was given immediately at the dose of 3 g/kg p.o. after the treatments. Drug wash
      out period of 10 days was maintained in between the successive tests to avoid the
      interference of action of the drug with the other. The non parametric data were
      analysed by Kruskal Wallis test. RESULTS: EAEMP produced a significant increase
      in the oral glucose tolerance test when compared with control and standard.
      CONCLUSION: Treatment with Melothria perpusilla lowers the blood glucose level
      due to higher oral glucose tolerance possibly due to release of insulin from the
      pancreas.

PMID- 28764194
TI  - Association between Single Nucleotide Polymorphisms of SMAD3 and BMP5 with the
      Risk of Knee Osteoarthritis.
AB  - INTRODUCTION: The role of genetic factors influencing osteoarthritis (OA)
      susceptibility is well documented and several candidate genes have been
      identified to be associated with it. Among these genes are Bone Morphogenetic
      Protein 5 (BMP5) and Smad family member 3 (SMAD3), all involved in Transforming
      Growth Factor (TGF) signaling pathway. The knee is the commonly affected joint,
      and knee OA has an especially high prevalence in Asian population. AIM: To
      investigate associations between Single Nucleotide Polymorphisms (SNPs)
      rs12901499 in SMAD3 and rs921126 in the BMP5 gene with knee OA susceptibility in
      and around Lucknow, Uttar Pradesh, India. MATERIALS AND METHODS: SNPs rs12901499
      in SMAD3 and rs921126 in BMP5 were genotyped in patients with knee OA and age-
      sex matched OA-free controls from our population. A total of 450 patients with
      knee OA and 458 controls were enrolled in the study. Venous blood samples were
      obtained from all cases as well as controls for PCR-RFLP (Polymerase Chain
      Reaction- Restriction Fragment Length Polymorphism). Data was collected and
      entered in excel sheets. Statistical analyses of the data were performed using
      statistical software package SPSS version 16.0. Chi-square, Student's t-test and
      logistic regression tests were used to analyse the data. RESULTS: GA and GG
      genotypes of both SNPs (rs12901499 and rs921126), and variant G, were associated
      with a significantly increased risk of knee OA. A significantly increased risk of
      knee OA was associated with the genotype GG and GA of rs12901499 (p < 0.03 and p
      <0.004 respectively) and rs921126 (p< 0.0001 and p<0.001 respectively) compared
      with the AA genotype. In addition, those bearing at least one G allele (GG + GA)
      had a significantly increased risk of knee OA compared with those without the G
      allele (AA) in rs921126 (p< 0.0001). However, in rs12901499, significant
      association with the risk of knee OA was not found (p<0.4). On age and gender
      based stratification, the association between the risk of OA and rs921126 GG
      mutant compared with AA homozygotes was strong in both gender (adjusted OR= 2.93
      for male and 2.25 for female) and in those aged >55 years (adjusted OR= 3.4),
      similarly in rs12901499, GG mutant compared with AA homozygote was strong in
      female (adjusted OR= 1.5) and in those aged >55 years (adjusted OR= 1.5).
      CONCLUSION: The results showed that both in SMAD3 rs12901499 and BMP5 921126, G
      allele is significantly associated with knee OA. A to G change and variant G
      genotype may contribute to knee OA risk in our study population of Lucknow.

PMID- 28764195
TI  - Whole-Exomes Sequencing Delineates Gene Variants Profile in a Young Saudi Male
      with Familial Hypercholesterolemia: Case Report.
AB  - Familial hypercholesterolemia is an autosomal dominant genetic disease
      characterized by earlier elevated Low-Density Lipoprotein (LDL) cholesterol
      levels and increased risk for premature Myocardial Infarction (MI). Albeit the
      diagnosis of some medical Familial Hypercholesterolemia (FH) cases are due to
      mutations in PCSK9, APOB, or LDLR, detection of mutation rate and profiles relies
      heavily on different gene pools and ethnicity. We ran exome sequencing on blood
      genomic DNA (gDNA) from a 26-year-old Saudi patient on Ion Proton Platform (Ion
      Torrent, Guilford, Connecticut, USA) as part of a pilot study preluding the
      establishment of the Saudi Human Genome project. The sequencing results were
      analysed using Ion suit Bioinformatics system. The patient was matched with a
      lady of lean body mass and Welsh descent, who suffered from hypercholesterolemia.
      The first analysis of known FH genes identified five mutations in APOB, 25
      mutations of known genes linked to FH, six mutations in LPR2, one mutation in
      LDLR, and three mutations in PCSK9. Finally, using disease filter algorithms, we
      filtered out more than 2000 intronic synonymous variants with likely no
      biological functions. No major new locus was found in FH. However, via variant
      reduction and TVC protocols we detected 15 new variants, among which 14 genes are
      linked to hypercholesterolemia, type-I, and type-II diabetes. We also detected
      three mutations in PCSK9 and confirmed one by Sanger. Taken together, this report
      suggests that the genetic determinant of FH in this Saudi patient is likely to be
      heterogeneous, complicating the diagnostic and novel gene discovery process.

PMID- 28764196
TI  - Adequate Resources as Essential Component in the Nursing Practice Environment: A
      Qualitative Study.
AB  - INTRODUCTION: Attracting and retaining well qualified nurses to develop
      healthcare systems and ensure patient safety is a global concern. In this regard,
      the quality of the practice environment plays a crucial role. AIM: To explore
      Iranian nurses perception on the key constituents of the nursing practice
      environment. MATERIALS AND METHODS: This study was conducted using a qualitative
      approach. Twelve participants were purposively selected from five teaching
      hospitals in Shiraz, Iran. Data was collected through semi structured interviews,
      and analysed using qualitative content analysis. RESULTS: Data analysis led to
      the extraction of two categories of 'adequate staff', with two subcategories of
      balanced workload and well qualified nurses, and 'adequacy of physical
      resources', with subcategories of equipment adequacy and appropriate physical
      structure as key elements of the nursing practice environment. CONCLUSION:
      Imbalanced workloads, inappropriate nurse-patient ratios, and inadequate physical
      resources negatively affected nurse's perceptions of the quality of the nursing
      practice environment. The findings provide baseline data for health policymakers
      in different national and global areas to remodel the practice environment. The
      improvement of the practice environment, with adequate staffing levels and
      appropriate allocation of physical resources, is achievable to resolve this
      challenge and thus improve outcomes.

PMID- 28764197
TI  - Peripheral Smear Review and Bone Marrow Biopsy Correlation.
AB  - INTRODUCTION: Peripheral Blood Smear (PBS) interpretation is a useful skill for
      Haematology/Oncology Clinicians (HOC). AIM: To explore practice patterns of PBS
      utilization for all benign haematology diagnosis in a non-simulated environment
      and to evaluate how it may guide the HOC in determining further work up and
      whether or not to perform a Bone Marrow Biopsy (BMB). MATERIALS AND METHODS: A
      retrospective review was conducted on 451 outpatient referrals for benign
      haematology diagnosis. Patient demographics and diagnostic tests were recorded.
      We further analysed cases in which a blood smear was ordered or reviewed. In
      cases with PBS review, we recorded testing ordered by the HOC. RESULTS: Records
      of 451 patients met inclusion criteria. The median age was 55 with males
      representing 51.9% of the cohort. Distribution of disorders were 50.6% (n = 228)
      erythrocyte (RBC), 25.5% (n = 114) leukocyte (WBC), 11.3% (n = 51) platelet
      (PLT), and 12.8% (n = 58) "other." A CBC was ordered in 82.7% of cases (373/451).
      A PBS was ordered in 47.4% of CBCs obtained (177/373, p<0.001). Of these,
      documentation occurred in 49.2% (87/177) which led to further testing 41.4% of
      cases (36/87). A BMB was performed in 11.5% (10/87) of cases in which a PBS was
      reviewed compared to 4.3% (16/373) of cases where BMB was performed without PBS
      review (p=.019). Of the 36 cases in which PBS review led to testing, 10 BMBs
      (27.8%) were performed-all of which led to specific haematologic diagnosis. A
      specific diagnosis was found in 43.8% (7/16) BMBs performed without prior PBS
      review. CONCLUSION: PBS interpretation is an important skill for HOCs.
      Haematology/Oncology (H/O) training programs should continue to teach this skill
      to increase proficiency in order to help guide diagnostic evaluation of various
      haematologic disorders.

PMID- 28764198
TI  - Investigating the Influence of Teachers' Characteristics on the Teacher-Student
      Relations from Students' Perspective at Ilam University of Medical Sciences.
AB  - INTRODUCTION: Establishing an effective teacher-student relationship may affect
      the quality of learning. Such a complex human relationship may be influenced by
      various factors in addition to teacher and student. AIM: The present study aimed
      at investigating the influence of teacher characteristics on the Teacher-student
      relationship from students' perspective. MATERIALS AND METHODS: In this
      descriptive-survey research, statistical population included 1500 students at
      Ilam University of Medical Sciences Ilam, Iran. Out of which 281 students were
      selected by simple random sampling, they received and completed series of
      questionnaires. Data was collected using a researcher-made questionnaire
      containing 37 Likert type items from which five items measured demographic
      profile of participants and 32 items measured impact of teacher's characteristics
      upon the teacher-student relationship. Data was analysed by SPSS software version
      16 using descriptive statistics, t-test and One way ANOVA. RESULTS: The current
      study included 281 students (117 (41.6%) male, 164 (58.4%) female) studying at
      Ilam University of Medical Sciences. The effect of teachers' characteristics on
      the teacher-student relationship from the students' perspective in three areas
      (personal, professional and scientific) scored 4.37+/-0.54, 4.05+/-0.27, and
      3.91+/-0.44, respectively. The highest score was related to "respect for
      students" (Mean=4.74, SD=0.55) and the lowest score was dedicated to 'gender'
      (Mean=2.40, SD= 0.64). Effect of other studied parameters was also higher than
      the average level. CONCLUSION: The findings indicated that teacher-student
      relationship and consequently the quality of education was overshadowed by the
      overall characteristics of teacher (namely-personal, professional and
      scientific). Notably, coupled with the professional and scientific properties of
      the teacher, his/ her communication skills may also help to provide a favourable
      learning condition for the students. Therefore, attention to the education of
      scientific as well as professional skills of the teachers in interaction with
      students through appropriate workshops and training courses is a matter of great
      necessity.

PMID- 28764199
TI  - Evaluation of Competencies Related to Personal Attributes of Resident Doctors by
      360 Degree.
AB  - INTRODUCTION: Postgraduate teaching involves training the residents in all
      spheres including professionalism, communication and interpersonal skills in
      addition to the basic clinical skills. Therefore, 360 degree evaluation has
      gained focus due to increased standards of medical care as shown in this study.
      AIM: To evaluate interpersonal and communication skills and professionalism in
      residents doctors using 360 degree evaluation method. MATERIALS AND METHODS: The
      present study was a descriptive study conducted at a tertiary care hospital
      affiliated with a medical college. Taking up as a pilot project, 26 residents
      from four departments were recruited in this study. A five point likert scale (1
      to 5,1 meaning poor, 5 meaning excellent) was used for scoring them on for their
      interpersonal and communication skills and professionalism by the persons working
      around their sphere like teachers, peers, nursing staff, undergraduate students
      and patients/or relatives (360 degree). RESULTS: Though the ratings by the peers
      and consultants were found to be slightly lower compared with nursing staff,
      undergraduate students and patients, there was good agreement between all of
      them. The mean score of all traits showed an increasing trend over the years of
      residency. CONCLUSION: Regular orientation programs for professionalism with 360
      degree evaluation and subsequent feedback to the resident doctor about their
      strength and weaknesses can definitely bring out behavioural change in the
      resident doctor in practice.

PMID- 28764200
TI  - Perception and Attitude of Medical Students towards Communication Skills Lab and
      Teaching Module.
AB  - INTRODUCTION: The knowledge of proper communication skills with the patients
      plays a pivotal role in success of medical professionals. A practical approach
      would be to initiate its training at an early stage of education period of
      undergraduate medical students. AIM: To assess perception and attitude of medical
      students towards Communication Skills Lab (CSL) and teaching module in Central
      India. MATERIALS AND METHODS: This cross-sectional study was conducted in
      Department of General Surgery at Index Medical College, Indore, India.
      Undergraduate medical students were trained as per a systematic teaching module
      in a well equipped 'CSL'. Feedback was obtained via Likert scale and analysed
      after completion of the training course of eight days. RESULTS: A majority of the
      students (96.43%) opined that the training had improved their communication with
      the patients. They also felt that such training should be integrated in regular
      teaching curriculum of our country. CONCLUSION: The training of basic
      communication skills can be introduced at an early stage of undergraduate medical
      curriculum in form of an effective, interesting and acceptable teaching module.

PMID- 28764201
TI  - The Need and Importance of Incorporating Academic Research Results in to the
      Curricula of Ayurveda in India.
AB  - Every year a noticeable number of MD and PhD students pass out from various
      Ayurveda colleges across the country. Each of these Post Graduate (PG) and
      doctoral students do submit a research thesis as a part of fulfillment of their
      respective degrees. As on 01/04/2015 there were 98 PG Ayurveda colleges in India
      with an admission capacity of 2441 seats each year. Moreover many of the post
      graduate institutes provide doctoral level (PhD) education which is primarily
      involved with research thesis. Such meticulous research carried out under the
      supervision of an academic expert should not go in vein and hence the research
      findings need to be slotted in to the respective areas and disciplines of
      Ayurveda syllabus. This will help in bringing in the latest scientific trends of
      Ayurveda to graduate students. Distressingly such practices are not in vogue in
      Ayurveda education system and most of the colleges follow the same stereotypic
      pedagogy using the classical texts of Ayurveda or their respective commentaries
      written decades back. Use of classical treatises and their respective
      commentaries offers very limited access to the recent scientific developments of
      Ayurveda as these commentaries are mostly one time efforts and do not undergo
      repeated revisions thus limiting the inclusion of present day innovations. In
      this commentary an effort has been made to understand the source, output, need
      and importance of such academic research finding with reference to their
      incorporation in to curricula of Ayurveda.

PMID- 28764202
TI  - Antimicrobial Effect of Leaves of Phyllanthus niruri and Solanum nigrum on Caries
      Causing Bacteria: An In vitro Study.
AB  - INTRODUCTION: Solanum nigrum and Phyllanthus niruri are common herbs which are
      indigeneous to India. Solanum nigrum commonly called 'manathakkali Keerai' in
      Tamil, forms an indispensable part of South Indian diet. Phyllanthus niruri
      (keezhanelli in Tamil) is a widely used medicinal plant, the leaves of which have
      been used extensively in Ayurveda and native medicine to cure various liver
      ailments. The herbs Solanumnigrum and Phyllanthus niruri have been found to be
      effective against numerous enteropathogens in various in vitro studies. AIM: To
      assess and compare the antibacterial efficacy of the crude alcoholic extract of
      the leaves of Solanum nigrum and Phyllanthus niruri against five cariogenic
      organisms. MATERIALS AND METHODS: Standard strains of the micro-organisms were
      obtained from ATCC (American Type Culture Collection) and MTCC (Microbial Type
      Culture Collection) which comprised of Streptococcus mutans MTCC no. 890,
      Streptococcus oralis MTCC no 2696, Lactobacillus acidophillus MTCC no. 10307,
      Streptococcus sanguis ATCC no. 10556 and Streptococcus salivarius ATCC no. 13419.
      The organisms obtained were revived and lawn cultured on Trypticase Soy Agar
      Blood Agar (TSA-BA) and de Man, Rogosa and Sharpe (MRS) agar media. The
      antibacterial effect of the dried and powdered leaves of Solanum nigrum and
      Phyllanthus niruri was tested using agar well diffusion method. The zones of
      inhibition obtained after incubation were measured and tabulated. The
      antibacterial activity for the two herbs was compared using the Mann-Whitney
      test. RESULTS: The antibacterial zones of inhibition obtained for the herb
      Solanum nigrum was in the range of 12.3-14.6 mm and ranged from 9.7-11.6 mm for
      the herb Phyllanthus niruri. When the zones of inhibition were compared for the
      herbs, Solanum nigrum showed significantly greater zones of inhibition compared
      to Phyllanthus niruri for the organisms Streptococcussanguis, Streptococcus
      salivarius, Streptococcus oralis and Streptococcus mutans (p-value<0.05).
      CONCLUSION: The alcoholic extract of leaves of Solanum nigrum and Phyllanthus
      niruri showed significant antibacterial activity against cariogenic organisms,
      with Solanum nigrum being more anti-cariogenic than Phyllanthus niruri.

PMID- 28764203
TI  - Use of Healthcare Services by Patients with Non-Communicable Diseases in Nepal: A
      Qualitative Study with Healthcare Providers.
AB  - INTRODUCTION: The healthcare systems in many Low-and Middle-Income Countries
      (LMICs) like Nepal have long focused on preventing and treating infectious
      diseases. Little is known about their preparedness to address the increasing
      prevalence of Non-Communicable Diseases (NCDs). AIM: This study aimed to
      investigate the use of healthcare services by patients with NCDs in Nepal.
      MATERIALS AND METHODS: Nine healthcare providers (including health assistants,
      pharmacy assistants, nurse, specialised nurse, practicing pharmacists, chief
      hospital pharmacist, doctors and specialised doctor) from Pokhara, Nepal, were
      recruited using purposive sampling. In depth interviews about the magnitude of
      NCDs, first point of care, screening and diagnosis, prevention and management,
      follow-up, and healthcare system responses to NCD burden were conducted. Data
      were thematically analysed with a deductive approach. RESULTS: Although the
      healthcare system in Nepal is still primarily focused on communicable infectious
      diseases, healthcare providers are aware of the increasing burden of NCDs and NCD
      risk factors. The first points of care for patients with NCDs are government
      primary healthcare facilities and private pharmacies. NCDs are often diagnosed
      late and opportunistically. NCD prevention and treatment is unaffordable for many
      people. There are no government sponsored NCD screening programs. CONCLUSION:
      There are problems associated with screening, diagnosis, treatment and follow-up
      of patients with NCDs in Nepal. Healthcare providers believe that the current
      healthcare system in Nepal is inadequate to address the growing problem of NCDs.
      The health system of Nepal will face challenges to incorporate programs to
      prevent and treat NCDs in addition to the pre-existing communicable diseases.

PMID- 28764204
TI  - Buccal Mucosa Carcinoma: A Comparative Relative Risk Analysis between Tobacco and
      Non Tobacco Users.
AB  - INTRODUCTION: In South India, buccal mucosa carcinoma is common cancer due to
      widespread use of tobacco in different form. Recently, areca nut (non tobacco)
      chewing habits have increased among young adults resulting in high morbidity and
      mortality. Thus, there is need to understand role of aetiology and risk of
      disease. AIM: To analyse relative risk of tobacco users and non tobacco users in
      buccal mucosa carcinoma. MATERIALS AND METHODS: This prospective comparative
      study was conducted in Regional Cancer Centre, Kanchipuram, between 2013 and
      2016. The subjects were divided as tobacco users and non tobacco users in order
      to evaluate the Relative Risk (RR) in these groups based on demographic and
      clinical characteristics by Chi-square analysis and Kaplan-Meier (log-rank test)
      applied for survival difference. All statistics considered at 95 % CI, p<0.05.
      RESULTS: A total of 117 subjects were included in the study which constituted 87
      (74.3%) tobacco users and 30 (25.7%) non tobacco users. In the study, demographic
      characteristics of gender [RR=0.365 (0.150-0.886), p=0.023] and age groups
      {RR=2.026 (0.905-4.996), p=0.04} showed significant difference in both study
      groups. Similarly, clinical characteristics of TNM (tumour node and metastasis)
      stage {RR=1.57 (0.338-3.31), p=0.024}, nodal status {RR=2.014 (0.412-4.454),
      p=0.017}, Grade of tumour {RR=1.293 (0.581-2.878), p=0.015}, perineural invasion
      {RR=2.601 (0.806-5.32), p=0.012} and extracapsular invasion {RR=1.627 (0.533
      2.824), p=0.045} showed significant association. The estimated overall survival
      was 50%; tobacco users (44%) showed lower survival than non tobacco users (57%)
      with significant difference (p=0.042, p<0.05). CONCLUSION: The study revealed
      adverse affect of aetiology on survival and showed lower survival of tobacco
      users than non tobacco users. Hence, the study concluded that the tobacco
      consumption in different form is more aggressive than non tobacco consumption.

PMID- 28764205
TI  - Prevalence and Patterns of Multimorbidity among Human Immunodeficiency Virus
      Positive People in Odisha, India: An Exploratory Study.
AB  - INTRODUCTION: Improved and efficient Anti-Retroviral Therapy (ART) has turned HIV
      positive into a chronic disorder. The increase in life expectancy and quality of
      life comes with an increased risk of multimorbidity from the traditional risk
      factors. AIM: To explore the prevalence of multimorbidity among People Living
      with HIV (PLHIV). MATERIALS AND METHODS: An exploratory cross-sectional study was
      carried out in an ART center of Odisha, India, from November 2013 to December
      2013. A systematic random sampling was done to include 197 adult HIV positive
      patients receiving ART at least for one year or more. A structured questionnaire
      was used to collect data on socio-demographic profile, ART status, multimorbidity
      and opportunistic infections. RESULTS: The prevalence of multimorbidity was 47.7%
      (95% CI 41% to 55%). Among them, the most common chronic conditions were
      pulmonary tuberculosis (28.4%), gastro-intestinal conditions (7.1%), neural
      disorders (5.1%) and hypertension (2.5%). In total, 48.7% had opportunistic
      infections; with 36% bacterial, 25% fungal and 21% viral infections. CONCLUSION:
      The prevalence of multimorbidity was high among HIV positive patients. Further
      research should explore the epidemiology of multimorbidity among HIV positive
      patients to formulate proper clinical practice guidelines to enhance long-term
      outcomes of PLHIV in the current treatment era.

PMID- 28764206
TI  - Analysis of Survival Data: Challenges and Algorithm-Based Model Selection.
AB  - Survival data is a special form of time to event data that is often encountered
      while modelling risk. The classical Cox proportional hazard model, that is
      popularly used to analyse survival data, cannot be used for modelling risk when
      the proportional hazard assumption is violated or when there is recurrent time to
      event data. In this context we conducted this narrative review to develop an
      algorithm for selection of advanced methods of analysing survival data in the
      above-mentioned situations. Findings were synthesized from literature retrieved
      from searches of Pubmed, Embase, and Google Scholar. Existing literature suggest
      that for non-proportionality, especially due to categorical predictors stratified
      Cox model may be useful. An accelerated failure time model is applicable in case
      of different follow-up time among different experimental groups and the median
      time to event is the outcome of interest instead of hazard. Extended Cox models
      and marginal models are used in case of multivariate ordered failure events and
      the type of model depends upon the presence of clustering and nature of ordering.
      In the presence of heterogeneity, a shared frailty model is used that is
      analogous to mixed models. More advanced models, including competing risk and
      multistate models are required for modelling competing risk, multiple states and
      multiple transitions. Joint models are used for multiple time dependent outcomes
      with different attributes. We have developed an algorithm based on the review for
      appropriate model selection to curb the challenge of modeling survival data and
      the algorithm is expected to help the naive researchers in analysing survival
      data.

PMID- 28764207
TI  - Correspondence: Comparative Efficacy of Oil Pulling and Chlorhexidine on Oral
      Malodor: A Randomized Controlled Trial.

PMID- 28764208
TI  - Assessing the Viability of Hadad Flap by Postoperative Contrast-Enhanced Magnetic
      Resonance Imaging.
AB  - INTRODUCTION: The Expanded Endonasal Approaches (EEAs) have been widely used for
      various skull base lesions. The reconstruction of the skull base defects is of
      vital importance to prevent postoperative complications. The vascular pedicled
      nasoseptal flap (Hadad-Bassagasteguy flap) is used as a workhorse in
      reconstruction of majority of the defects. AIM: The purpose of this study was:
      (a) To assess the postoperative MRI appearance of vascularised pedicled
      nasoseptal flap for its viability; (b) To determine the variations in MRI that
      may suggest potential flap failure. MATERIALS AND METHODS: A prospective study of
      13 patients was done, who underwent endoscopic skull base surgery with
      reconstruction using the Hadad-Bassagasteguy flap. Pre-operative MRI was done to
      assess the size, extent and location of the lesion and a postoperative MRI was
      done to evaluate flap configuration, enhancement patterns, location, flap
      thickness and signal intensity characteristics. RESULTS: The postoperative MRI of
      all patients showed a detectable flap covering over the skull base defects
      forming an "open cup" appearance. They were uniformly isointense on T1-weighted/
      fat suppressed images to the adjacent nasal mucosa and hyperintense on T2
      weighted images. On the MRI scans done after four weeks, all 13 of our patients
      had enhancing flaps. One flap migrated slightly to the left side; however, there
      was no Cerebrospinal Fluid (CSF) leak. CONCLUSION: Vascular pedicle nasoseptal
      (Hadad) flaps are being widely used. MRI is a very useful tool in assessing the
      viability of the flap postoperatively and to evaluate for variations that may
      suggest potential flap failure.

PMID- 28764209
TI  - Mastoid Osteoma of Temporal Bone - A Rare Case Report.
AB  - Osteomas of the temporal bone are rare entity with incidence of 0.1% - 1% of all
      benign tumours of skull. They are slow growing benign lesion of temporal bone. We
      report a rare case of mastoid osteoma of size more than 5 cm. A 40-year-old
      female patient presented to us with left post auricular bony swelling of size
      greater than 5 cm. Diagnosis of mastoid osteoma was made after relevant
      investigations including High Resolution Computed Tomography (HRCT) temporal
      bone. Complete surgical excision was done with good cosmetic outcome without
      recurrence.

PMID- 28764210
TI  - Kimura's Disease without Peripheral Eosinophilia: An Unusual and Challenging Case
      Simulating Venous Malformation on Imaging Studies-Case Report and Review of
      literature.
AB  - Kimura's Disease (KD) is a rare chronic inflammatory disorder presenting as
      multiple painless solitary subcutaneous nodules, predominantly in the head and
      neck region and frequently associated with regional lymphadenopathy and/or
      salivary gland involvement. Because of painless nature and indolent course, there
      is usually a delay in the patient's presentation. KD may radiologically mimic
      other chronic inflammatory conditions like tuberculosis, vascular malformations
      and neoplasms. Clinical correlation and histological evaluation along with
      elevated peripheral eosinophil and serum IgE level are considered important for
      confirmatory diagnosis. We report a case of painless swelling over right
      submandibular region extending to the right superficial parotid. The
      haematological reports were within normal limits. Ultrasound (USG), Magnetic
      Resonance Imaging (MRI) and Magnetic Resonance Angiogram (MRA) favoured a
      diagnosis of venous malformation. However, histopathological examination of
      excised lesion confirmed a diagnosis of KD. This case proves the possibility of
      the KD even in the absence of peripheral eosinophilia and/ or elevated serum IgE
      level, and may mimic venous malformation on imaging studies. Therefore, KD must
      find a place in the differentials of solitary painless neck swelling even in the
      absence of peripheral eosinophilia and/or elevated IgE level.

PMID- 28764211
TI  - A Rare Case of Topiramate Induced Secondary Acute Angle Closure Glaucoma.
AB  - Secondary Acute Angle Closure Glaucoma (AACG) is a known side effect of
      Topiramate (TPM). Here, we present a case report of a 47-year-old male who was
      started on TPM 25 mg/day for migraine. He presented to the ophthalmology
      department of our hospital with sudden blurring of vision and colored halos after
      one day of starting TPM. A high index of suspicion, followed by appropriate
      investigations and prompt management that helped to manage TPM induced bilateral
      AACG with quick and complete visual recovery.

PMID- 28764212
TI  - Congenital Ectropion Uveae with Glaucoma: A Case Report.
AB  - Congenital Ectropion Uveae (CEU) is a rare anomaly characterised by ectropion
      uveae, iris hypoplasia, iridotrabecular dysgenesis and glaucoma. Hyperplasia of
      the iris pigment epithelium and its apparent spread over the anterior surface of
      the iris is supposed to cause the classic ectropion uveae in CEU. Almost all
      patients develop open angle glaucoma due to angle dysgenesis, so they should be
      carefully examined periodically for its early detection. We hereby report a case
      of isolated unilateral CEU without any systemic association which is quite
      uncommon. Loss of vision went unnoticed while the facial asymmetry secondary to
      progressive enlargement of one eye became the presenting complain due to this
      rare unilateral affliction.

PMID- 28764213
TI  - An Unusual Presentation of Conjunctival Infection.

PMID- 28764214
TI  - Study of Retinal Nerve Fibre Layer Thickness and Visual Contrast Sensitivity in
      HIV Positive Individuals.
AB  - INTRODUCTION: Measurement of Retinal Nerve Fibre Layer Thickness (RNFLT) by
      Optical Coherence Tomography (OCT) is a sensitive, non invasive and cheap method
      of detecting early retinal changes in a variety of diseases. In HIV infection,
      RNFLT is altered and this may have effect on other visual functions like Contrast
      Sensitivity (CS) and visual acuity. Such ocular pathology can affect the daily
      life and profession (especially driving) of HIV infected individuals. However,
      studies on this topic in HIV infected population are rare from India. AIM: To
      study RNFLT, CS and their correlation in a sample of HIV positive Indian
      population. MATERIALS AND METHODS: The present cross-sectional study was done in
      a tertiary care medical college hospital of Eastern India between May 2016 and
      September 2016. We did this study on HIV positive subjects with no clinically
      apparent ocular infection or other pathology. In this study, we have measured the
      RNFLT using the HRA-OCT Spectralis machine. The CS was tested using a smartphone
      version of the Pellie-Robson chart. CD4 count, visual acuity and colour vision
      were also tested. The data was analysed using SPSS version 20.0 for any
      correlation between these parameters. Pearson coefficient was used for continuous
      data and Spearman rank correlation was used for categorical data. A p-value <0.05
      was considered significant. RESULTS: We had 17 patients, that is 34 eyes. RNFLT
      loss was found in 21% of the eyes and borderline thinning was found in a further
      26%. Predominantly, the temporal quadrant was involved. The mean of log CS was
      1.33+/-0.38. Taking 1.5 as the cut-off value for normalcy, 47% of the eyes tested
      showed decreased CS. Log CS showed significant correlation with RNFLT of the
      temporal quadrant only (r=0.37; 95% C.I. 0.041 to 0.631; p=0.02). Temporal RNFLT
      also showed statistical correlation with the CD4 count. The low CS was also
      significantly correlated with low visual acuity (r=0.5). CONCLUSION: In HIV
      infected persons, subtle ocular changes may occur and this may affect visual
      functions quite early. Hence, a comprehensive eye check-up should include
      parameters like CS and OCT.

PMID- 28764216
TI  - Association Between Left Ventricle Diastolic Dysfunction and Unfavorable
      Prognostic Markers in Patients with Aortic Insufficiency.
AB  - INTRODUCTION: The presence of symptoms, systolic dysfunction and Left Ventricle
      (LV) dilation are considered unfavourable prognostic markers in Aortic Valve
      Insufficiency (AVI). The role of diastolic dysfunction, which is considered
      unfavourable outcome marker in cardiac pathologies, is not well established in
      AVI. AIM: To evaluate if the presence of diastolic dysfunction may be associated
      with unfavourable prognostic markers in AVI patients. MATERIALS AND METHODS: A
      cross-sectional prospective study was performed on 22 patients with moderate or
      severe AVI. They underwent clinical evaluation and transthoracic
      echocardiography. Associations between clinical, epidemiological and
      echocardiographic were evaluated by Student t-test for normally distributed
      variables or Mann-Whitney test for non-normal distribution. Comparison between
      proportions was performed by Chi-square test. RESULTS: There was an association
      between increased LV filling pressure, assessed by E' and E/E' of Mitral Tissue
      Doppler, and impaired LV systolic function, respectively: R = 0.563, R2 = 0.281;
      p = 0.008 and R = 0.639, R2 = 0.378; p = 0.002. The LV indexed mass also was
      inversely associated with the LV ejection fraction (R = 0.62, R2 = 0.35 and p =
      0.003). CONCLUSION: There was an association of LV diastolic dysfunction and
      ventricular hypertrophy with impaired left ventricle systolic function. Increased
      LV filling pressure and LV indexed mass should be considered in the management of
      AVI patients.

PMID- 28764215
TI  - Comparative Evaluation of Accuracy of Pulse Oximeters and Factors Affecting Their
      Performance in a Tertiary Intensive Care Unit.
AB  - INTRODUCTION: Pulse oximetry is a widely used tool, unfortunately there is a
      paucity of data investigating its accuracy in Intensive Care Units (ICU) and if
      they are able to meet mandated FDA criteria as claimed by them in critically ill
      patients. AIM: To assess bias, precision and accuracy of pulse oximeters used in
      ICU and factors affecting them. MATERIALS AND METHODS: A prospective cohort
      study, including 129 patients admitted to the ICU of a tertiary referral centre.
      Pulse oximetry and blood gas were done simultaneously. Pulse oximetry was done
      using two pulse oximetres: Nonin and Philips. All physiological variables like
      haemoglobin, lactate, use of vasopressors and blood pressure were recorded. Bland
      Altman curves were constructed to determine bias and limits of agreement. Effect
      of physiological variables on bias and difference between performance
      characteristics of bias was determined using SPSS. RESULTS: Pulse oximetry
      overestimated arterial oxygen saturation (SaO2) by 1.44%. There was negative
      correlation between bias and SaO2 (r=-0.32) and positive correlation with lactate
      (r=0.16). The Philips pulse oximeter had significant higher bias and variability
      than Nonin pulse oximeter. (2.49+/-2.99 versus 0.46+/-1.68, mean difference =
      1.98, 95% C.I. = 1.53 - 2.43, p-value <0.001). CONCLUSION: Pulse oximetry
      overestimates SaO2. Bias tends to increase with rising lactate and hypoxia. There
      is heterogeneity in performance of various pulse oximetry devices in ICU.

PMID- 28764217
TI  - Performance of Disease-Specific Scoring Models in Intensive Care Patients with
      Severe Liver Diseases.
AB  - INTRODUCTION: Egypt has the highest prevalence of Hepatitis C Virus (HCV) in the
      world, estimated nationally at 14.7%. HCV treatment consumes 20% ($80 million) of
      Egypt's annual health budget. Outcomes of cirrhotic patients admitted to the ICU
      may, in fact, largely depend on differences in the state of the disease, criteria
      and indications for admission, resource utilization, and intensity of treatment.
      AIM: The aim of the present study was to evaluate the efficacy of liver specific
      scoring models in predicting the outcome of critically ill cirrhotic patients in
      the ICU as it may help in prioritization of high risk patients and preservation
      of ICU resources. MATERIALS AND METHODS: Over one year, a total of 777 patients
      with End Stage Liver Disease (ESLD) due to HCV infection were included in this
      retrospective non-randomized human study. All statistical analyses were performed
      by the statistical software SPSS version 22.0 (SPSS, Chicago, IL, USA). Child
      Turcotte Pugh (CTP) score, MELD score, MELD-Na, MESO, iMELD, Refit MELD and Refit
      MELD-Na were calculated on ICU admission. RESULTS: ICU admission was mainly due
      to Gastrointestinal (GI) bleeding and Hepatic Encephalopathy (HE). Overall
      mortality was 27%. Age and sex showed no statistical difference between survivors
      and non survivors. Significantly higher mean values were observed for all models
      among individuals who died compared to survivors. MELD-Na was the most specific
      compared to the other scores. MELD-Na was highly predictive of mortality at an
      optimized cut-off value of 20.4 (AURC=0.789+/-0.03-CI 95%=0.711-0.865) while
      original MELD was highly predictive of mortality at an optimized cut-off value of
      17.4 (AURC=0.678+/-0.01-CI 95%=0.613-0.682) denoting the importance of adding
      serum sodium to the original MELD. INR, serum creatinine, bilirubin, white blood
      cells count and hyponatremia were significantly higher in non survivors compared
      to survivors, while hypoalbuminemia showed no statistical difference. The advent
      of Hepatorenal Syndrome (HRS) and Spontaneous Bacterial Peritonitis (SBP) carried
      worse prognosis. Hyponatremia and number of transfused blood bags were additional
      independent predictors of mortality. CONCLUSION: In cirrhosis of liver, due to
      HCV infection, patients who died during their ICU stay displayed significantly
      higher values on all prognostic scores at admission. The addition of sodium to
      MELD score greatly improves the predictive accuracy of mortality. MELD-Na showed
      the highest predictive value of all scores.

PMID- 28764218
TI  - Sepsis Mortality in Critical Care and Prior Statin Therapy: A Retrospective
      Cohort Study in Central Argentina.
AB  - INTRODUCTION: Sepsis is a major public health problem, frequent, costly, and
      often fatal. Despite of improvements in supportive treatments the incidence of
      sepsis and the number of deaths related to sepsis is increasing. Statins have
      been recently proposed as adjuvants in the treatment of sepsis, but its effects
      on mortality show conflicting results worldwide. AIM: The purpose of this study
      was to describe the clinical outcome of patients diagnosed with sepsis in a
      university-affiliated hospital in central Argentina and to evaluate it in
      relation to a group of septic patients with previous use of statins before the
      onset of sepsis. MATERIALS AND METHODS: The present study was conducted as an
      observational retrospective research from April 2010 to December 2014 with
      patients over 18 years of age which were assigned to statins or control groups.
      Out of 2906 patients, 231 matched study and diagnostic criteria for sepsis and
      among them 33 (14.3%) belonged to the group of statins. The mean age was 64.2 +/-
      14.3 years. RESULTS: The severity of sepsis on admission was as follows: Sepsis,
      n=147 (63.6%), Severe sepsis, n=26 (11.3%) and Septic shock, n=58 (25.1%). The
      mean length of stay in Intensive Care Unit (ICU) was10.8 +/- 9.6 days and 21.2 +/
      17 days in general hospital ward settings, without differences between groups of
      statin users and controls, p=0.873 and p=0.766, respectively. The in-hospital
      mortality rate was 31.2% (n=72). Previous statin use did not affect in-hospital
      or 30-day mortality (OR 0.978; 95% CI 0.339 to 2.274; p=0.789). Creatinine levels
      on days 3 and 14 were substantially higher in statins group (1.80 +/-1.39 vs.
      1.45 +/- 1.47 mg/dl) (p=0.010) and (1.42 +/- 1.14 vs. 1.09 +/- 1.05 mg/dl)
      (p=0.009), respectively. CONCLUSION: Prior use of statins did not reduce in
      hospital or 30-day mortality in septic patients and it may be associated with
      impaired renal function in this group of Argentinian participants.

PMID- 28764219
TI  - Teneligliptin in Early Diabetic Kidney Disease: An Observation in Asian Indian
      Patients with Type 2 Diabetes Mellitus in Real-Life Scenario.
AB  - INTRODUCTION: Teneligliptin is a recently developed Dipeptidyl Peptidase 4 (DPP4)
      inhibitor. Teneligliptin is suitable for glycaemic control with renal impairment
      including end stage renal disease. AIM: To assess the efficacy and safety of
      teneligliptin in Asian Indian patients of Type 2 Diabetes Mellitus (T2DM) with
      early Diabetic Kidney Disease (DKD). MATERIALS AND METHODS: This was a single
      centre, retrospective analysis of patients with early DKD, who received
      teneligliptin 20 mg once daily for 24 weeks. Data related to glycaemic
      parameters, kidney function, lipid levels, retinopathy, neuropathy and safety
      variables available at 12 and 24 weeks were analysed. Descriptive statistical
      analysis was carried out. Statistical significance was assessed at a 5% level.
      RESULTS: Total 37 patients (21 males; 16 females) were analysed. Compared to
      baseline, significant reduction in Fasting Plasma Glucose (FPG) (mg/dl) (143.89+/
      28.26 vs. 125.78+/-20.52, p=0.001); Postprandial Glucose (PPG) (mg/dl) (200.62+/
      41.88 vs. 165.76+/-26.02, p=0.001); Glycated Haemoglobin (HbA1c) (%)(8.65+/-0.58
      vs. 8.17+/-0.54, p=0.001) was noted at 12 weeks. This trend was further continued
      for 24 weeks with significant reduction in mean FPG, PPG and HbA1c to 113.73+/
      16.82 mg/ dl (p=0.008); 142.95+/-20.76 mg/dl (p=0.001); and 7.65+/-0.45%
      (p=0.001) respectively. Significant improvement in serum creatinine (mg/dl)
      (2.45+/-0.27 vs. 2.26+/-0.23, p=0.001) and eGFR (CKD-EPI), (ml/min/1.73 m2)
      (53.35+/-4.24 vs. 55.08+/-4.19, p=0.001) was noted at 12 weeks and continued for
      24 weeks with reduction in serum creatinine of 0.37+/-0.18 mg/ dl (p=0.001) and
      increase of eGFR of 4.60+/-1.59 ml/min/1.73 m2 (p=0.001). At baseline,
      proteinuria was noted in all patients while at 24 weeks, 40.5% (p=0.001) patients
      did not report proteinuria. Significant improvements in lipid parameters with no
      deterioration in retinopathy and subjective improvement in peripheral neuropathy
      was also noted. No adverse events were noted. CONCLUSION: Teneligliptin reported
      significant and sustained improvement in glycaemic control in Asian Indian
      Patients of T2DM with early DKD and was well tolerated. Additionally,
      Teneligliptin reported significant improvement in renal function.

PMID- 28764220
TI  - To Evaluate the Change in Brain Natriuretic Peptide Levels in Outpatients with
      Ischemic Cardiomyopathy and Its Association with Functional Capacity: A Pilot
      Study.
AB  - INTRODUCTION: Literature is sparse on the clinical correlation of six minute walk
      test (6MWT) and Brain Natriuretic Peptide (BNP) levels in ischemic Cardiomyopathy
      (Ischemic CMP) patients. New York Heart Association (NYHA) classification is most
      commonly used for functional assessment of Heart Failure (HF), which is very
      subjective. This limitation is overcome by 6MWT which has prognostic significance
      in addition to assessment of level of functional impairment. Serum BNP correlate
      with clinical severity of HF as assessed by NYHA class. AIM: To evaluate the
      change in BNP levels in outpatients with ischemic CMP and its association with
      functional capacity. MATERIAL AND METHODS: Sixty seven patients of established
      ischemic CMP by coronary angiography With Left Ventricular Ejection Fraction
      (LVEF) <40%, were recruited on an Outpatients Department (OPD) basis and assessed
      for baseline BNP levels and functional capacity (NYHA class and 6MWT). These
      patients were managed on OPD basis and the treatment was optimised and all the
      aggravating factors like uncontrolled diabetes, hypertension and anaemia were
      corrected. Patients were also advised life style modifications and cessation of
      smoking and alcohol consumption. All these patients were followed up for six
      months with optimum medical treatment and repeat 6MWT and BNP levels. Primary end
      point was change in the functional class and the BNP levels at six months.
      Statistical analysis was done with paired t-test and Pearson correlation for BNP
      levels and 6MWT/NYHA class. RESULTS: A total of 67 patients were enrolled, out of
      which 48 patients had six months follow up. Thirty two patients were in NYHA
      Class II and remaining was in NYHA Class III at the time of enrollment. At six
      months, 37 were in NYHA Class II and 11 in Class III. At enrollment, 37 cases
      were able to walk >300 m in six minutes and 11 cases walked < 300 m where as at
      six months 43 walked >300 m and five walked <300 m. As compared to baseline the
      mean distance covered in 6MWT showed significant improvement and with reduction
      in BNP levels at six months (p<0.001). Mean BNP levels correlated better with
      6MWT (p <0.001) than NYHA class (p<0.67). CONCLUSION: In patients with
      established ischemic CMP with LVEF <40%, there is a significant reduction in BNP
      levels and improvement in 6MWT at six months with optimum medical therapy. A 6MWT
      correlated better with BNP levels than with NYHA class with a significant p
      value. However, larger such studies and a longer duration of follow up is
      desirable to prove this association.

PMID- 28764221
TI  - Maximal Aortic Valve Cusp Separation and Severity of Aortic Stenosis.
AB  - INTRODUCTION: An integrated approach that incorporates two dimensional, M mode
      and Doppler echocardiographic evaluation has become the standard means for
      accurate quantification of severity of valvular aortic stenosis. Maximal
      separation of the aortic valve cusps during systole has been shown to correlate
      well with the severity of aortic stenosis measured by other echocardiographic
      parameters. AIM: To study the correlation between Maximal Aortic valve Cusp
      Separation (MACS) and severity of aortic valve stenosis and to find cut-off
      values of MACS for detecting severe and mild aortic stenosis. MATERIALS AND
      METHODS: In the present prospective observational study, we have compared the
      accuracy of MACS distance and the aortic valve area calculated by continuity
      equation in 59 patients with varying degrees of aortic valve stenosis. Aortic
      leaflet separation in M mode was identified as the distance between the inner
      edges of the tips of these structures at mid systole in the parasternal long axis
      view. Cuspal separation was also measured in 2D echocardiography from the
      parasternal long axis view and the average of the two values was taken as the
      MACS. Patients were grouped into mild, moderate and severe aortic stenosis based
      on the aortic valve area calculated by continuity equation. The resultant data
      regarding maximal leaflet separation on cross-sectional echocardiogram was then
      subjected to linear regression analysis in regard to correlation with the peak
      transvalvular aortic gradient as well as the calculated aortic valve area. A cut
      off value for each group was derived using ROC curve. RESULTS: There was a strong
      correlation between MACS and aortic valve area measured by continuity equation
      and the peak and mean transvalvular aortic gradients. Mean MACS was 6.89 mm in
      severe aortic stenosis, 9.97 mm in moderate aortic stenosis and 12.36 mm in mild
      aortic stenosis. MACS below 8.25 mm reliably predicted severe aortic stenosis,
      with high sensitivity, specificity and positive predictive value. MACS above
      11.25 mm practically ruled out significant aortic stenosis. CONCLUSION:
      Measurement of MACS is a simple echocardio-graphic method to assess the severity
      of valvular aortic stenosis, with high sensitivity and specificity. MACS can be
      extremely useful in two clinical situations as a simple screening tool for
      assessment of stenosis severity and also helps in decision making non invasively
      when there is discordance between the other echocardiographic parameters of
      severity of aortic stenosis.

PMID- 28764223
TI  - Frequency of Polyneuropathy in Patients on Long Term Peritoneal Dialysis
      Treatment.
AB  - INTRODUCTION: Uremic polyneuropathy is very common among patients with Chronic
      Kidney Disease (CKD). The patients have electrophysiologic signs of impaired
      nerve function, although a lower percentage of patients are symptomatic.
      Electrophysiological parameters are quantitative indices of Polyneuropathy (PNP)
      severity. AIM: To assess the frequency of PNP in patients on long term Peritoneal
      Dialysis (PD) treatment. MATERIALS AND METHODS: Twenty three PD patients were
      analysed, who were receiving dialysis for at least five years and the study
      population divided into two groups according to duration of PD treatment. Group 1
      consisted of the patients who were dialysed for at least 10 years and Group 2
      consisted of patients who were dialysed for five to nine years. Patients who
      switched from Haemodialysis (HD) to PD and patients with coexisting diseases that
      could lead to disturbances in nerve conduction were excluded from the study. PNP
      was diagnosed when slowing of Nerve Conduction Velocity (NCV) and/or lengthening
      of distal latencies and/or decrease in amplitude of muscle action potential were
      present in two or more nerves and longer F wave response was present in one or
      two nerves. Carpal Tunnel Syndrome (CTS) was diagnosed if slowing of NCV and/or
      decrease in amplitude of muscle action potential and/or lenghening of distal
      latency of either sensory or motor median nerve present. RESULTS: PNP was
      observed in 17 of the patients {73.9%; Group 1 (n=10) and Group 2 (n=7)}. Mixed
      type sensory motor neuropathy was diagnosed in nine patients from Group 1 and
      five patients from Group 2; one patient from Group 1 had demyelinating PNP
      affecting motor and sensory nerves; one patient from Group 2 had axonal PNP
      affecting motor and sensory nerves. From Group 1, two patients had CTS related to
      PNP and one patient had CTS without PNP. The results of motor conductivity
      testing showed lower conduction velocity for left popliteal nerve in Group 1 and
      Group 2 patients (13.85+/-2.17 ms, 4.80+/-1.11 ms, p=0.01). In both groups, mean
      motor and sensory latency, amplitude and velocity of other nerves were not found
      to be significantly different (p>0.05). CONCLUSION: PNP is a common complication
      in long term PD patients. Over five years of treatment, frequency of PNP and CTS
      do not increase with duration of dialysis.

PMID- 28764222
TI  - Evaluation of Myocardial Injury using Standard Diagnostic Tools and Tissue
      Doppler Imaging in Blunt Trauma Chest.
AB  - INTRODUCTION: Myocardial contusion is an entity in chest trauma which is
      difficult to diagnose. Current practice relies more on cardiac-specific
      biochemical markers and standard echocardiography, but no gold standard test
      exists. The application of Tissue Doppler imaging is yet unexplored. AIM: The
      present study was designed to evaluate cardiac injury in patients with blunt
      trauma chest using conventional trans-thoracic echocardiography parameters and
      Tissue Doppler imaging. MATERIALS AND METHODS: After ethical approval was taken
      from the Hospital and University and a written informed consent from all
      patients/attendants, this prospective study was conducted on a total of 30
      patients in range of 15-60 years of age with blunt trauma chest. Patients with
      positive Trop-T and raised CPK (> 308 IU/L), raised CK-MB (> 24 IU/L) levels were
      suspected to have myocardial injury and were enrolled in the study. All patients
      fulfilling the inclusion criteria then underwent 2D-Echo and Tissue Doppler
      Imaging. Results of the observations were analysed using chi-square test.
      RESULTS: Out of the total of 30 patients, 63.3% showed ECG changes suggestive of
      cardiac injury. A 76.7% patients suffered systolic dysfunction and 36.6% patients
      suffered diastolic dysfunction irrespective of ECG changes. On comparison of
      early filling velocity wave i.e., E wave (measured by transthoracic
      echocardiography) and tricuspid annular velocity Em wave (measured by tissue
      Doppler echocardiography) at tricuspid valve, we found statistically significant
      difference among two techniques. (p = 0.04). CONCLUSION: Echocardiography is very
      sensitive parameter for evaluation of myocardial contusion. Tissue Doppler
      imaging provides additional and reliable information.

PMID- 28764224
TI  - Paroxysmal Atrial Fibrillation due to Venomous Snake Bite.
AB  - Snake bites are common all around the world with a great prevalence in South Asia
      and the Indian subcontinent. Although they are associated with common
      complications such as local swelling, bleeding at site of bite, coagulopathy,
      etc., few rare cardiac complications such as myocardial infarctions and
      arrhythmias have also been described in literature. The following is a case
      report of a patient who had a snake bite with a Russell's viper which resulted in
      atrial fibrillation, which resolved on treatment with anti snake venom.

PMID- 28764225
TI  - An Unusual Cause of Organizing Pneumonia: Hydrocarbon Pneumonitis.
AB  - Hydrocarbon pneumonitis is a type of acute exogenous lipoid pneumonia due to the
      aspiration of petroleum products. The clinical and radiological features of this
      condition are non-specific and the diagnosis is usually missed if a careful
      history is not taken. Herein, we describe a 24-year-old male who was referred to
      us with a diagnosis of Interstitial Lung Disease (ILD) and was later found to
      have hydrocarbon pneumonitis.

PMID- 28764226
TI  - Cisplatin Induced Acute Myocardial Infarction and Dyslipidemia.
AB  - Myocardial infarction commonly occurs due to rupture of atherosclerotic plaque in
      the coronary arteries and is manifested on coronary angiography. Myocardial
      infarction with angiographically normal coronary arteries can occur due to
      hypercoagulable state, coronary spasm, embolism, arteritis, congenital condition
      and drugs. Illicit drugs such as cocaine, amphetamines and marijuana are known to
      cause myocardial infarction. Of the many medications that are associated with
      cardiovascular toxicity, chemotherapeutic agents form a large group with both
      acute and delayed cardiotoxicity. We present a case of acute myocardial
      infarction in a patient with no organic coronary artery disease on the Bleomycin,
      Etoposide and Cisplatin (BEP) regimen for treatment of testicular seminoma.
      Patient developed symptoms of Acute Coronary Syndrome (ACS) after his third cycle
      of the regimen. This case highlights the need for prior careful cardiovascular
      evaluation, close monitoring and use of strategies to prevent cardiovascular
      morbidity in patients on cisplatin therapy.

PMID- 28764227
TI  - Portal Venous Thrombosis-Disseminated Tuberculosis in Rheumatoid Arthritis.
AB  - Vascular thrombosis is one of the complications of tuberculosis. Deep vein
      thrombosis and pulmonary thrombosis have been reported with pulmonary and
      extrapulmonary tuberculosis. Splenic involvement in abdominal tuberculosis is
      among the rarest manifestations. Disseminated tuberculosis is predominantly
      reported in rheumatoid arthritis following ingestion of biological agents. Here,
      we report a case of disseminated tuberculosis in a rheumatoid arthritis patient
      who was on steroids and methotrexate for a long period, presenting with multiple
      splenic lesion and portal vein thrombosis, which was not reported earlier. She
      was treated with antitubercular drugs, anticoagulants and showed improvement.

PMID- 28764228
TI  - Idiopathic Brachial Neuritis in a Patient with Multiple Myeloma.
AB  - Idiopathic Brachial Neuritis (IBN), is a rare brachial plexopathy with an unknown
      aetiology. Multiple myeloma is a neoplastic plasma cell disease characterised by
      bone lesions. In this article, we present the case of a 59-year-old male patient
      with IBN associated with multiple myeloma, who was admitted to our clinic with
      right shoulder pain and right arm weakness. He experienced muscle weakness and
      atrophy in his right arm after a sudden onset of pain attack in the shoulder.
      Plexus and cervical vertebral MRI showed no pathology. Electrodiagnostic studies
      showed upper and middle trunk plexopathies. Laboratory analysis revealed anaemia,
      hypercalcaemia, renal dysfunction and monoclonal gammopathy in immunoglobulin
      electrophoresis. A bone marrow biopsy established the diagnosis of IgG kappa
      multiple myeloma. This is the first case report that presents the association of
      multiple myeloma and IBN.

PMID- 28764229
TI  - Upper Gastrointestinal Bleed as a Manifestation of Poorly Differentiated
      Metastatic Squamous Cell Carcinoma of the Lung.
AB  - Gastrointestinal (GI) metastasis from primary lung cancer is a rare clinical
      finding. Lung cancer most often metastasizes to the brain, bone, liver, and
      adrenal glands; with gastrointestinal involvement being very rare. We report a
      case of a 39-year-old female with a diagnosis of poorly differentiated Squamous
      Cell Carcinoma (SCC) of the lung presenting with dizziness and melena.
      Esophagogastroduodenoscopy (EGD) showed a bleeding mass in the stomach. Final
      biopsy report and Immunohistochemistry (IHC) of the specimen were consistent with
      SCC lung metastasis. While it is imperative to have a high clinical suspicion for
      GI metastasis in patients with primary lung cancer presenting with GI symptoms,
      it may be challenging to establish diagnosis. Endoscopy along with pathology and
      immunohistochemistry play a crucial role in differentiating primary GI
      malignancies from metastasis.

PMID- 28764230
TI  - Pulmonary Actinomycosis in a Patient with AIDS/HCV.
AB  - Pulmonary actinomycosis is a rare bacterial lung infection which is caused mainly
      by Actinomyces israelii. This non contagious infection can destroy parts of the
      lungs. There are variable presentations of pulmonary actinomycosis with
      similarity in manifestations to other infectious diseases of the lungs. Pulmonary
      actinomycosis is diagnosed by fine needle aspiration, bronchoscopy and finding of
      typical sulfur granules. We present a case of pulmonary actinomycosis in a middle
      aged (AIDS/HCV) man with massive hemoptysis and progressive dyspnoea. The
      bronchoscopy findings showed endobronchial mass with luminal occlusion in right
      upper lobe. Because of massive hemoptysis and poor response to conservative
      treatment and penicillin therapy, right upper lobectomy was needed to stop the
      bleeding. Histopathologic examination revealed the aggregations of filamentous
      Gram-positive organisms with characteristic pattern "sulfur granules", indicating
      actinomycosis. The patient was followed by six months of oral amoxicillin and has
      no recurrent hemoptysis.

PMID- 28764231
TI  - Large Isolated Major Aortopulmonary Collateral Artery Causing Severe Pulmonary
      Hypertension in an Infant: A Rare and Challenging Diagnosis.
AB  - Major Aortopulmonary Collateral Artery (MAPCA) as an isolated congenital anomaly,
      without evidence of any structural heart disease, is a very rare observation.
      Previously published reports indicate that symptomatic infants with large
      isolated MAPCA usually present with congestive heart failure or recurrent
      respiratory tract infections. To the best of our knowledge, the present case of
      an infant with large isolated MAPCA is a unique case with a diagnostic dilemma
      due to presentation with severe pulmonary hypertension as a predominant sign. The
      infant was managed successfully by percutaneous obliteration with amplatzer
      vascular plugs, along with perioperative and postoperative sildenafil.

PMID- 28764232
TI  - Co-Inheritance of Haemoglobin D-Punjab and Beta Thalassemia - A Rare Variant.
AB  - Haemoglobinopathies are a frequent cause of anaemia in Northwestern India due to
      traditional practices of consanguineous marriages. Haemoglobin D-Punjab is one of
      the most common subvariants (55%) of haemoglobin D, which can be inherited as a
      homozygous or a heterozygous trait with other haemoglobinopathies. Though,
      haemoglobin D-Punjab is commonly seen, a heterozygous trait with beta thalassemia
      is a very rare presentation. Here, we present a rare case of co-inheritance of
      haemoglobin D-Punjab and beta thalassemia in a 19-year-old male of Indian origin.
      He came with gradually progressive generalised weakness with easy fatigability
      for the past two months. No history of similar complaints in the past. On
      examination, he was pale and icteric with splenomegaly and Grade I hemorrhoids on
      systemic examination. On investigation, there was severe anaemia, pancytopenia
      (mixed picture on smear), vitamin B12 deficiency and raised Lactate Dehydrogenase
      (LDH). Haemoglobin electrophoresis showed co-inheritance of haemoglobin D-Punjab
      and beta thalassemia. After Pack Cell Volume (PCV) and B12 supplements,
      haemoglobin improved. He was counseled about his disease and advised regular
      follow-up.

PMID- 28764233
TI  - Multifocal Tubercular Dactylitis: A Rare Presentation of Skeletal Tuberculosis in
      an Adult.
AB  - Tubercular dactylitis is an uncommon form of osteo-articular tuberculosis seen in
      children. Multifocal involvement, simultaneously involving hands and feet is
      extremely uncommon. Here we report an adult patient with tubercular dactylitis
      involving multiple digits of both hands and second digit of right foot in absence
      of any risk factors like immunodeficiency or any debilitating condition. The
      patient was successfully treated with anti-tubercular drugs for six months.
      Mycobacterium tuberculosis infection of bones and joints can present in an
      unusual way but early diagnosis and treatment caries a good prognosis.

PMID- 28764234
TI  - Basic Concepts and Clinical Outcomes of Drug-Eluting Balloons for Treatment of
      Coronary Artery Disease: An Overview.
AB  - The technology of percutaneous coronary intervention for atherosclerotic coronary
      artery disease has evolved considerably since its inception. Though Drug-Eluting
      Stent (DES) reduces the rate of restenosis, long-term safety outcomes and
      persistent restenosis in complex lesion subset remain area of concern. Recently,
      Drug-Eluting Balloon (DEB) represents a novel treatment strategy for
      atherosclerotic coronary artery disease. DEB demonstrated its added value in
      preclinical studies. Inspired by these results, several clinical trials
      particularly in complex lesion subsets have been started to explore the value of
      this novel treatment strategy in a broader range of lesions. This review would
      summarise material compositions and different characteristics and clinical
      outcomes of currently available DEB.

PMID- 28764235
TI  - Immunodiagnosis of Human Fascioliasis: An Update of Concepts and Performances of
      the Serological Assays.
AB  - Human Fascioliasis (HF) is a foodborne neglected parasitic disease caused by
      Fasciola hepatica and Fasciola gigantica. New epidemiological data suggest that
      the endemic areas of the disease are expanding and HF is being reported from
      areas where it was previously not observed. Diagnosis of HF is challenging.
      Performances of parasitological approaches, based on the detection of parasite's
      egg in the stool, are not satisfactory. Currently serological methods for the
      diagnosis of HF are mainly based on detection of anti-Fasciola antibodies in
      serum. Although, there have been some improvement in the development of
      immunological diagnostic tests for the diagnosis of HF, yet these tests suffer
      from insufficiency in sensitivity or/and specificity. Detection of antigens,
      rather than antibodies, seems to be a suitable approach in the diagnosis of HF.
      Antigen can be detected in sera or stool of the fascioliasis patients.
      Circulating antigen in serum disappears within a short time and most of the
      circulating antigens are in immune complex forms which are not freely available
      to be detected. Therefore, antigenemia might not be an appropriate method for the
      diagnosis of HF. Detection of antigen in stool (coproantigens) seems to be a
      suitable alternative method for the diagnosis of HF. Recent data provided
      convincing evidence that detection of coproantigen improved and simplified the
      diagnosis of HF. The present review highlights the new achievements in designing
      and improvement of diagnostic approaches for the immunodiagnosis of HF. Moreover,
      current status of the available immunodiagnostic techniques for the diagnosis of
      HF, their strengths and weaknesses has been discussed.

PMID- 28764236
TI  - Clinical Significance of the Forsaken aVR in Evaluation of Tachyarrhythmias: A
      Reminder.
AB  - INTRODUCTION: Mechanism of a regular, monomorphic Wide QRS Complex Tachycardia
      (WCT) is an important diagnostic challenge in day to day practice for the
      clinicians and affects further management and prognosis. Many of the WCT and
      Narrow Complex Tachycardia (NCT) produce certain characteristic changes in lead
      aVR by which we can differentiate between them. AIM: The present study was aimed
      to evaluate tachyarrhythmias in relation to lead aVR and to highlight the
      clinical significance of lead aVR, "The Neglected Lead". MATERIALS AND METHODS:
      This is prospective study in which 55 consecutive cases of tachyarrhythmias
      excluding sinus tachycardia, atrial fibrillation and atrial flutter were taken
      for the study admitted in from ICCU of Department of Medicine at S.S. Medical
      College and S.G.M. Hospital Rewa (M.P.), India, during July 2014 to September
      2015, fulfilling the required study protocol. The data was collected regarding
      detailed history, physical examination; necessary investigations (including ECG
      and echocardiography) were done. RESULTS: Among 55 patients, 30 were of WCT and
      25 were of NCT. The most common cause of WCT was Ventricular Tachycardia (VT)
      (83.3%) and rest were Supra Ventricular Tachycardia (SVT) with aberrancy (16.7%).
      The most common cause of NCT was Atrioventricular Nodal Tachycardia (AVNRT) (84%)
      followed by Atrioventricular Reciprocating Tachycardia (AVRT) (16%). The present
      study observed that 38.1% of the AVNRT cases and 50% of AVRT cases showed
      positive 'p' wave in lead aVR. The present study observed that 75% cases of AVRT
      showed ST segment elevation in lead aVR while only 33.3% cases of AVNRT showed ST
      elevation. In the present study 80% of the patients with WCT were diagnosed to
      have VT using Brugada algorithm while using Vereckei's new aVR algorithm, 83.3%
      were diagnosed to have VT. CONCLUSION: Lead aVR, one of the most neglected leads
      on 12 lead ECG, is a very important diagnostic tool for identification and
      categorization of different type of tachyarrhythmias. The presence of ST
      elevation in lead aVR on ECG showing NCT is relatively sensitive for diagnosing
      AVRT. New aVR algorithm by Vereckei is more sensitive for differential diagnosis
      of WCT. One should pay careful attention to lead aVR which provides essential
      diagnostic information.

PMID- 28764237
TI  - Local Injection of Triamcinolone Acetonide: A Forgotten Aetiology of Cushing's
      Syndrome.
AB  - Many different non systemic corticosteroid administrations can cause iatrogenic
      Cushing's Syndrome (CS). We herein report a case series of iatrogenic CS from
      keloid scars treatment and aesthetic regimen called mesotherapy. Our first
      patient developed CS after having exceeded recommended dose of intralesional
      injection of Triamcinolone Acetonide (TAC). Second case presented with CS
      followed by unidentified mesotherapy treatment for local fat reduction.
      Subcutaneous injections of dexamethasone were found to be the part of mesotherapy
      regimen in one case. Physicians should be insightful in prescribing TAC
      especially in those patients who have high predisposing factors for developing
      CS. In the same way, off-label mesotherapy combine with corticosteroid can lead
      to iatrogenic CS and Hypothalamic-Pituitary-Adrenal (HPA) axis suppression.
      Currently, there are no standard guidelines for mesotherapy treatment. Therefore,
      further clinical trials on dosage, duration and effective combination of
      mesotherapy regimens are needed to increase safety uses.

PMID- 28764238
TI  - Plasma Cell Disorders in HIV Infected Patients: A Case Series.
AB  - People Living with HIV (PLHIV) are at an increased risk of developing
      malignancies. Plasma cell disorders are also reported with increased incidence in
      PLHIV compared to the general population. Here, we describe three different
      plasma cell disorders among PLHIV and highlight their atypical presentations and
      outcomes in these subjects.

PMID- 28764239
TI  - Single Layered Versus Double Layered Intestinal Anastomosis: A Randomized
      Controlled Trial.
AB  - INTRODUCTION: Gastrointestinal anastomosis is one of the most common procedures
      being performed in oesophagogastric, hepatobiliary, bariatric, small bowel and
      colorectal surgery; however, the safety and efficacy of single layer or double
      layer anastomotic technique is still unclear. AIM: To assess and compare the
      efficacy, safety and cost effectiveness of single layered versus double layered
      intestinal anastomosis. MATERIALS AND METHODS: This prospective, double-blind,
      randomized controlled comparative study comprised of patients who underwent
      intestinal resection and anastomosis. They were randomly assigned to undergo
      either single layered extra-mucosal anastomosis (Group-A) or double layered
      intestinal anastomosis (Group-B). Primary outcome measures included average time
      taken for anastomosis, postoperative complications, mean duration of hospital
      stay and cost of suture material used; secondary outcome measures assessed the
      postoperative return of bowel function. Statistical analysis was done by Chi
      square test and student t-test. RESULTS: A total of 97 participants were
      randomized. Fifty patients were allocated to single layered extramucosal
      continuous anastomosis (Group-A) and 47 patients to double layered anastomosis
      (Group-B). The patients in each group were well matched for age, sex and
      diagnosis. The mean time taken for anastomosis (15.12+/-2.27 minutes in Group-A
      versus 24.38+/-2.26 minutes in Group-B) and the length of hospital stay (5.90+/
      1.43 days in Group-A versus 7.29+/-1.89 days in Group-B) was significantly
      shorter in Group-A {p-value <0.001}. The postoperative return of bowel function
      was quicker in the single layer group (2.42+/-1.11 days) as compared to the
      double layer group (3.1+/-1.34 days). The cost of suture material used was
      relatively more in the single layered group (564 INR vs. 480 INR) which might be
      the only factor favoring a double layered anastomosis. However, there was no
      significant difference in the complication rates between the two groups.
      CONCLUSION: It can be concluded that single layered extramucosal continuous
      intestinal anastomosis is equally safe and perhaps more cost effective than the
      conventional double layered method and may represent the optimal choice for
      routine surgical practice.

PMID- 28764240
TI  - Factors Hindering Practice of Day Care Surgery in a Tertiary Care Centre in
      Southern India: A Patient's Perspective.
AB  - INTRODUCTION: Day care surgery offers cost containment, effective usage of
      hospital beds, reduced incidence of nosocomial infection and early recovery in
      home environment. In developing countries like India, there are various factors
      that influence the success of day care surgery. AIM: To assess the factors
      hindering the practice of day care surgery in a tertiary care centre in South
      India. MATERIALS AND METHODS: This observational study was conducted in the
      Department of General Surgery, JIPMER, Puducherry, India, from January 2013 to
      March 2014. All male patients with uncomplicated inguinal hernia who were
      admitted for elective surgery under one particular surgery unit and who were
      found fit for discharge on Postoperative Day 1 (POD1) based on clinical fitness
      were included in the study. A questionnaire containing the patient's acceptance
      decision, VAS (Visual Analogue Scale) pain score and the reason for non
      acceptance if any was used for assessment. RESULTS: Among the 89 patients who
      were fit for discharge on POD1, the decision for discharge was accepted by 57
      patients. 32 patients were not satisfied of the decision for discharge on POD1.
      The common reasons for dissatisfaction with the decision were persistent pain at
      operated site (13 patients with mean VAS score 8.3), non availability of health
      care resources in their locality (12 patients) and unwillingness to travel on
      POD1 (four patients). CONCLUSION: A comprehensive and well presented preoperative
      counselling along with an effective primary health service would help in
      promoting day care surgery in developing countries.

PMID- 28764241
TI  - Small Intestinal Lymphangioma Presenting as an Acute Abdomen with Relevant Review
      of Literature.
AB  - Cystic lymphangioma of small bowel mesentery is rare with clinical features
      ranging from an asymptomatic abdominal lump to acute intestinal obstruction. We
      discuss two cases of lymphangioma of small bowel mesentery who presented to us as
      acute intestinal obstruction. In the first case exploratory laparotomy revealed a
      large multicystic lesion arising from small bowel mesentery just distal to the
      duodenojejunal junction having multiple small cysts filled with milky white
      fluid. The involved region of the bowel was excised. The second case had a large
      multicystic lesion involving the mesentery of proximal jejunum, dudenojejunal
      junction, encasing the entire superior mesenteric vessels. For this patient,
      debulking was done.

PMID- 28764242
TI  - Page Kidney in Wunderlich Syndrome Causing Acute Renal Failure and Urosepsis:
      Successful Timely Minimally Invasive Management of a Devastating Clinical Entity.
AB  - Wunderlich Syndrome (WS) is an uncommon condition where acute onset of
      spontaneous bleeding occurs into the subcapsular and perirenal spaces. It can
      prove fatal if not recognized and treated aggressively at the appropriate time. A
      32-year-old male diagnosed elsewhere as acute renal failure presented with tender
      left loin mass, fever and hypovolemic shock with serum creatinine 8.4 mg/dl. He
      was started on higher antibiotics and initiated on haemodialysis. Ultrasonogram
      (USG), Non-Contrast Computed Tomography (NCCT) and Magnetic Resonance Imaging
      (MRI) showed bilateral perirenal subcapsular haematomas - right 3.6 x 3.1 cm and
      left 10.3 x 10.3 cm compressing and displacing left kidney, fed by capsular
      branch of left renal artery on CT angiogram. Initial aspirate was bloody but he
      persisted to have febrile spikes, renal failure and urosepsis and he was managed
      conservatively. Repeat NCCT 10 days later revealed left perinephric abscess and
      Percutaneous Drainage (PCD) was done. Patient improved, serum creatinine
      stabilized at 2 mg/dl without haemodialysis and PCD was removed after two weeks.
      To conclude, bilateral idiopathic spontaneous retroperitoneal haemorrhage with
      renal failure is a rare presentation. This case highlights the need for high
      index of suspicion, the role of repeated imaging and successful minimally
      invasive management with timely PCD and supportive care.

PMID- 28764243
TI  - Necrotizing Fasciitis: A Rare Complication of Acute Necrotizing Pancreatitis.
AB  - Necrotizing pancreatitis occurs in 10 to 25% of patients requiring hospital
      admission for acute pancreatitis and carries a high mortality rate. Necrotizing
      pancreatitis can cause a spectrum of complications. However, we report an
      extremely rare complication of necrotizing pancreatitis: necrotizing fasciitis of
      the abdominal wall. A 56-year-old male patient presented to our center with
      discoloration of skin over left flank of 15 days duration and pus discharge from
      it since three days. Two months back he was managed at a private hospital as a
      case of acute necrotizing pancreatitis and was discharged after one week of
      inpatient treatment. After discharge patient continued to have malaise and
      weakness but was able to do his routine day to day activity. On presentation at
      our hospital, patient was in septic shock and was taken emergently to operating
      theatre for debridement. However, later, the patient succumbed to his illness.
      Necrotizing fasciitis is an extremely uncommon complication of necrotizing
      pancreatitis and has a fulminant course. Timely detection and debridement can
      avert a potential mortality.

PMID- 28764244
TI  - A Rare Case of Intestinal Malrotation and Volvulus of Jejunum with Coexisting
      Carcinoid Tumour of Appendix.
AB  - Malrotation of the midgut is generally regarded as a paediatric pathology. It is
      rare in adults. Patients may present with symptoms of acute bowel obstruction or
      chronic abdominal pain. Barium study, Contrast Enhanced Computed Tomography
      (CECT), Magnetic Resonance Imaging (MRI), diagnostic laparoscopy and sometimes
      explorative laparotomy are used for diagnosis. Ladd's procedure through the open
      approach has been the treatment of choice for complete malrotation of midgut,
      however there are reports on successful outcome for both complete and incomplete
      malrotation after laparoscopic approach as well. We report a case of a 25-year
      old female who presented with a history of severe pain in abdomen for one week.
      CECT abdomen showed incomplete malrotation and volvulus in midgut. Laparoscopic
      detorsion of bowel loops, adhesiolysis, caecopexy and appendectomy was done.
      Patient's symptoms subsided immediately after surgery. Histological analysis of
      the appendix specimen showed small appendiceal carcinoid, which was purely
      incidental. At three months follow up, patient was symptom free.

PMID- 28764245
TI  - Bilateral Staghorn Calculus with Forgotten Double J Stent in Ileal Conduit
      Patient - A Rare Urological Challenge.
AB  - Forgotten DJ stent associated stone formation is not an uncommon entity. Here we
      are reporting the uncommon case of bilateral staghorn calculus due to forgotten
      DJ stent who had undergone radical cystectomy with ileal conduit diversion six
      years back. Management of these cases is a challenging urological situation due
      to inaccessible ureteric orifices. Patient was successfully treated with
      minimally invasive therapy in the form of combined bilateral PCNL (Percutaneous
      Nephrolithotomy) and ESWL (Extracorporeal Shock Wave Lithotripsy) therapy. The
      purpose of reporting this case is to highlight the grave consequences of a
      forgotten DJ stent and to discuss the difficulties encountered during the
      surgical steps of stone removal.

PMID- 28764246
TI  - A Report of Two Cases of "Giant Bartholin Gland Cysts" Successfully Treated by
      Excision with Review of Literature.
AB  - Bartholin's gland cysts are one of the common vulval masses that may start as
      asymptomatic cysts but if left untreated, may become large and infected requiring
      medical attention. We are presenting two interesting and rare cases of giant
      Bartholin cyst and their treatment in this case report. Two female patients of
      perimenopausal age presented with giant vulval cysts to the outpatient department
      of Obstetrics and Gynaecology. They reached a size of 10 cm and 20 cm diameter
      respectively, presenting with some diagnostic and later reconstruction of the
      labia majus. MRI pelvis provided good information regarding the size, shape and
      extent of the cyst, which was very useful during surgery. Both these cases were
      successfully treated by excision of the cyst and histopathological examination
      after complete excision. One of the cases presented as dumb-bell shaped swelling
      with large cyst superiorly and smaller cyst extending into the buttock connected
      by narrow neck and showed cross fluctuation. This type of dumb-bell shaped
      presentation of Bartholin's cyst is rather unusual and has not been reported in
      the available literature.

PMID- 28764247
TI  - Idiopathic Granulomatous Mastitis: A Clinical Puzzle in Breast Lump Cases.
AB  - Idiopathic granulomatous mastitis (IGM) is a rare benign disease, characterized
      by chronic inflammation and granulomatous disease process. A middle aged lady
      with breast lump for six months with equivocal mammographic and ultrasound
      results underwent lumpectomy and biopsy. Ruling out all other possible
      granulomatous diseases and malignancy, a diagnosis of IGM was made. IGM becomes
      clinically significant as it closely mimics carcinoma breast and some
      inflammatory and infectious pathology.

PMID- 28764248
TI  - Wunderlich Syndrome due to Ruptured Pseudoaneurysm of Angiomyolipoma in First
      Trimester: A Rare Case Report.
AB  - Angiomyolipoma (AML) is a rare benign tumour of kidney which demonstrates rapid
      growth during pregnancy due to hormonal stimulation, leading to rupture. Majority
      of reported ruptured AMLs are in third trimester. We report a case of ruptured
      angiomyolipoma at 10th week of gestation, the earliest rupture known in singleton
      pregnancy. The AML had pseudo-aneurysm formation with extra-tumoural rupture
      during pregnancy, a finding never reported in literature yet. The patient had
      active bleeding with expanding peri-nephric haematoma during initial two days of
      conservative management. Hence, after counselling and taking prior informed
      written consent for Medical Termination of Pregnancy (MTP), computed tomography
      scan of abdomen with angiography followed by emergency coil embolization of the
      bleeding right upper polar segmental artery was done. After stabilization, MTP
      was done at 12th week of gestation. Counselling and consent for continuing or
      aborting the pregnancy is of utmost importance for best possible outcome for
      patient and foetus.

PMID- 28764249
TI  - Bile Duct Adenocarcinoma with Acute on Chronic Pancreatitis: A Rare Complication
      of Long Standing Choledochal Cyst.

PMID- 28764250
TI  - Microtia in All the Siblings of a Family: A Rare Case.

PMID- 28764251
TI  - Rickettsial Fever Presenting with Gangrene: A Case Series.
AB  - Rickettsial diseases comprise a wide spectrum of diseases which are reported from
      different parts of India quiet long ago. Many cases of rickettsial diseases go
      undiagnos due to lack of diagnostic techniques and the reported incidence and
      prevalence may be an underestimation of the actual burden of the disease. A
      higher index of suspicion, clinical awareness and proper use of available
      diagnostic tools would increase the frequency of diagnosis. Gangrene is an
      uncommon complication in cases of rickettsial fever. Extensive gangrene of the
      digits or whole limb, even requiring amputation has been more commonly reported
      with Rocky Mountain spotted fever. These cases are being reported to highlight
      the occurrence of gangrene in rickettsial fever and the importance of appropriate
      management at the earliest.

PMID- 28764252
TI  - Effects of Counselling and Sole Reflexology on Fatigue in Pregnant Women: A
      Randomized Clinical Trial.
AB  - INTRODUCTION: Increase of fatigue may lead to problems during pregnancy, delivery
      and post delivery. Sole reflexology is the application of pressure to areas on
      the feet. Reflexology is generally relaxing and may be an effective way to
      alleviate fatigue and stress. AIM: To investigate the effect of counselling and
      sole reflexology on fatigue in pregnant women, referred to the medical centers of
      Hamadan city, Iran. MATERIALS AND METHODS: This study was a randomized clinical
      trial with three groups - Group A (counselling and reflexology), Group B
      (reflexology) and Group C (control) with pre and post intervention. A total of
      forty two pregnant women were selected for each group. Measurement tool was a 30
      question standard checklist for fatigue assessment. For all three groups, an
      explanatory session was held to get their written consents and conduct a pretest.
      The intervention included five education sessions, twice a week about reflexology
      in the form of counselling and sole reflexology. The groups were assessed
      immediately after intervention. Data were analysed using IBM SPSS Statistics
      20.0. To analyse the data, descriptive statistics, t test and ANOVA with repeated
      measures were used. RESULTS: In group A and group B, the mean score of fatigue
      severity after the intervention demonstrated a significant decrease (p<0.05);
      furthermore, after intervention, a significant difference was observed between
      the control and experimental groups in terms of fatigue severity (p<0.01).
      CONCLUSION: Based on the results of this study, counselling and sole reflexology
      significantly decreased fatigue in pregnant women. It is hoped that the results
      of this study can be used by all treatment groups and midwives for controlling
      and providing midwifery cares for pregnant women.

PMID- 28764253
TI  - Enhanced Expression of FRA16B using AT-Rich DNA Binding Chemicals in a Woman with
      Secondary Amenorrhoea.
AB  - Fragile sites represent regions of chromatin that fail to compact during mitosis.
      Based on the prevalence and pattern of inheritance they are classified as rare
      fragile sites or common fragile sites. Rare fragile sites either occur
      spontaneously or can be induced by certain AT-specific binding chemicals namely
      distamycin, Hoechst 33258, Berenil and others. The most common of all rare
      autosomal fragile sites is fra(16)(q22) with a heterozygote frequency of ~5%.
      FRA16B results from an expansion of a 33 bp AT-rich Minisatellite repeat. These
      rare forms are usually heritable and segregate in a Mendelian fashion. The
      proband who was referred for secondary amenorrhoea, revealed
      46,XX,fra(16)(q22.1)pat karyotype. Her father and younger sibling were also found
      to be carriers. This study aimed to delineate the genotypic and phenotypic
      features exhibited by these carriers and to evaluate FRA16B expression using AT
      specific binding chemicals. The additives employed were Berenil, BrdU and Hoechst
      33258. Berenil at a concentration of 150 ug/ml showed the highest expression of
      FRA16B. Although the recent breakthrough in molecular characterization of fragile
      sites plays a critical role in comprehending their association with various
      diseases, the physiological link between them and amenorrhoea is not clearly
      understood.

PMID- 28764254
TI  - Role of Provisional Fixation of Fracture Fragments By Steinmann-Pin and Technical
      Tips in Proximal Femoral Nailing for Intertrochanteric Fracture.
AB  - INTRODUCTION: Proximal Femoral Nailing (PFN) in Intertrochanteric Fractures (IF)
      is becoming the choice of implant due to better biomechanics and prevention of
      varus collapse associated with Dynamic Hip Screw (DHS). Technical difficulties
      and implant related complications are yet to be addressed. AIM: To understand the
      technical difficulties involved in PFN and role of provisional fixation of
      fracture by Steinmann-pin. MATERIALS AND METHODS: In this study, 55 patients
      presented to a tertiary trauma center in India with trochanteric fractures from
      April 2010 to March 2012 were included and treated with PFN. All patients were
      followed-up for two years and final outcome assessment included shortening, neck
      shaft angle and Harris Hip Score was done. RESULTS: In all except one, neck shaft
      angle greater than 130 degrees  was achieved and also maintained in the final
      follow up (Mean 131.1 degrees ). All fractures were united with mean shortening
      of 3.6 mm and average Harris Hip Score of 91 after two years. There were five
      complications which included one shortening, two varus collapses, one backed out
      screws and one reverse Z effect. CONCLUSION: Though PFN is technically
      challenging, with proper technique, gives excellent results with negligible varus
      collapse even in unstable fractures. Three most important technical aspects are
      achieving good non-varus reduction, inserting nail correctly and accurate
      placement of lag screws. The technique of provisional fixation of fracture
      fragments by Steinmann-pin significantly helps in achieving these and reduces the
      risk of implant failure.

PMID- 28764255
TI  - Atraumatic Acute Compartment Syndrome of Forearm Following Artificial Mehndi
      (Henna) Dermatitis - A Rare Case Report.
AB  - Atraumatic compartment syndrome of the forearm is a rare entity. There are
      several papers available in the literature on the adverse effects of mehndi
      application; however Acute Compartment Syndrome (ACS) following mehndi
      application has never been reported. We present the case of a 25-year-old female,
      who presented with sudden onset swelling and pain in the left forearm. The
      patient had applied mehndi all over her left palm and forearm just two days prior
      to presentation. The patient had stretch pain and other clinical features
      suggestive of compartment syndrome of forearm and was hence taken up for an
      emergency fasciotomy. The fasciotomy wound healed without skin grafting and the
      patient achieved near normal range of movement of the affected elbow, wrist and
      fingers.

PMID- 28764256
TI  - Lead Level in Umbilical Cord Blood and its Effects on Newborns Anthropometry.
AB  - INTRODUCTION: High concentration of blood lead is accompanied by adverse health
      effects on growth of foetus and the newborn. AIM: The aim of this study was to
      determine umbilical cord blood lead level and its relationship with birth weight,
      length and head circumference of the newborns in Abadan, Iran. MATERIALS AND
      METHODS: In this cross-sectional study, 3 ml blood was collected from the
      umbilical cord vein in 147 newborns, immediately after the birth. Blood lead was
      measured using atomic absorption spectrophotometry. Data collection instruments
      included demographic questionnaire (age of mother, gestational age, newborn
      gender, job and education of mother) and also data registration form (umbilical
      cord blood lead concentration, weight, length, and head circumference of
      newborn). Data was analyzed with SPSS software version 16.0. RESULTS: The mean of
      umbilical cord blood lead was determined 0.65+/-0.32 ug/dl (0.3-1.35 ug/dl). The
      decrease of birth weight with increased blood lead level was small and was not
      statistically significant. There was reverse significant correlation between
      umbilical cord blood lead level and birth length and head circumference. There
      was no significant correlation between blood lead and other variables such as
      age, weight, education and job of mother and gestational age. CONCLUSION:
      Umbilical blood lead level was determined <5 ug/ dl. Excess of umbilical cord
      blood lead caused decreasing birth weight, length and head circumference of the
      newborns.

PMID- 28764257
TI  - A Randomized Comparison between Video Demonstration and Verbal Instruction in
      Improving Rota Haler Technique in Children with Persistent Asthma: A Pilot Study.
AB  - INTRODUCTION: Inhalation therapy is the cornerstone in management of asthma.
      Failure to use the device properly is one of the factors incriminated in poor
      control of asthma. AIM: To compare the technique of rota haler use in children
      with persistent asthma immediately after receiving either verbal instruction or a
      video based demonstration and again at one month following intervention.
      MATERIALS AND METHODS: A total of 28 children, older than six years attending the
      childhood asthma clinic of our hospital, who were prescribed rota halers for the
      first time and who were technique naive were enrolled into the study, after
      obtaining informed consent from the parents after meeting inclusion and exclusion
      criteria. They were then randomly assigned to either verbal instructions (group
      of 14) or video demonstration group (group of 14), for teaching them the rota
      haler technique. Their technique was then assessed using a modified version of
      the inhaler device assessment tool immediately after education and one month
      after the intervention. The proportions of children with good technique in both
      groups at both time points were compared. RESULTS: There was no significant
      difference in the baseline variables like age, gender, location, socio-economic
      status and disease duration between both groups. The proportion of children
      achieving good technique was significantly more in the video group than the oral
      instruction group at immediate assessment and also at one month post intervention
      with an odds of 8 and 23.40 respectively (p=0.0262 and 0.0075 respectively).
      CONCLUSION: Video demonstration is effective in improving the technique of rota
      haler use at immediate assessment and at one month post intervention. Further
      studies are needed to validate this study and to assess factors that predict
      successful device use.

PMID- 28764258
TI  - Apple-Peel Intestinal Atresia Along with Isolated Jejunal Duplication Cyst in a
      Newborn - An Extremely Rare Case Report and Brief Review.
AB  - Apple-peel type of intestinal atresia and non-communicating jejunal duplication
      cyst are rare congenital malformations. The coexistence is not reported in
      English literature. A five-day-old female neonate having intestinal obstruction
      and was found to have both the anomalies during laparotomy and was successfully
      managed. Being an extremely uncommon association between two congenital anomalies
      of gastrointestinal tract and surgical emergencies, it is reported with review of
      relevant literature.

PMID- 28764259
TI  - Survey of Diagnostic Criteria for Fetal Distress in Latin American and African
      Countries: Over Diagnosis or Under Diagnosis?

PMID- 28764260
TI  - Significance of Foetal Transcerebellar Diameter in Foetal Biometry: A Pilot
      Study.
AB  - INTRODUCTION: The most important parameter needed for appropriate management of
      pregnant women is accurate Gestational Age (GA). Routine sonographic estimation
      of GA by using Biparietal Diameter (BPD), Femur Length (FL), Abdominal
      Circumference (AC) and Head Circumference (HC) assumed important role in
      management of pregnancy. However, these parameters have limitations. BPD and HC
      are not reliable in case of moulding of foetal head in third trimester.
      Similarly, femur length is shortened in cases of achondroplasia. Transcerebellar
      Diameter (TCD) was developed as an alternative parameter of foetal brain growth
      and for estimation of GA. AIM: To evaluate accuracy of predicting GA using Foetal
      Transcerebellar Diameter (TCD) and to compare between TCD and other existing
      parameters in evaluating GA in 15 to 40 weeks of gestation. MATERIALS AND
      METHODS: A prospective study was carried out in 100 pregnant women between 15 to
      40 weeks of gestation, who came for routine antenatal sonography. Transcerebellar
      diameter was measured along with routine parameters. Subjects were divided into
      two groups based on GA (15-28 and 29-40 weeks). Gestational age using TCD and
      other parameters was calculated and compared with gestational age based on Last
      Menstrual Period (LMP). Correlation between the GA by LMP with GA by other
      ultrasound parameters was done by using Karl Pearson's Correlation(r). RESULTS:
      In 15-28 weeks, all parameters had nearly equal r-values. Among all parameters,
      TCD revealed highest correlation with value of 0.997. In 29-40 weeks, there was
      considerable difference in r-values. An r-value of 0.982 was noted, when the GA
      by TCD and LMP was compared, r-value of which is more than the other parameters.
      The least correlation was seen with BPD, r=0.951. The second most accurate
      correlation was seen with the FL with r-value of 0.981. CONCLUSION: TCD is an
      accurate parameter in estimation of gestational age in second and third
      trimesters as its values are in close relation with that of GA by LMP. It is also
      better predictor of the gestational age when compared to other parameters
      especially in third trimester.

PMID- 28764261
TI  - Role of Multivoxel Intermediate TE 2D CSI MR Spectroscopy and 2D Echoplanar
      Diffusion Imaging in Grading of Primary Glial Brain Tumours.
AB  - INTRODUCTION: Preoperative tumour grading is imperative owing to difference in
      invasive, aggressive tendencies of different grades of glial tumours implying
      varied prognosis, therapeutic options. Histopathological examination has inherent
      sampling errors. Magnetic Resonance Spectroscopy (MRS) and Diffusion Weighted
      Imaging (DWI) can provide non invasive information about internal mileu hence,
      aiding in tumour grading by adding to information provided by conventional MRI
      sequences. AIM: To evaluate the role of multivoxel intermediate TE 2D CSI MRS and
      2D echoplanar diffusion imaging in grading of primary glial brain tumours.
      MATERIAL AND METHODS: A prospective study was conducted in Department of
      Radiology, Teerthanker Mahaveer Medical College and Research Centre, Uttar
      Pradesh, India, from April 2015 to August 2016 after obtaining necessary
      approvals from Institutional Ethical Committee and written informed consent from
      all participants on histopathological proven cases of glial brain tumours that
      underwent multivoxel MRS using intermediate TE 2D chemical shift imaging and DWI
      using 2D echoplanar imaging. Tumour grade calculated on MRI using MRS and DWI was
      compared with histopathological grading. Positive Predictive Value (PPV),
      Negative Predictive Value (NPV), Sensitivity, specificity and accuracy were
      calculated for each parameter and statistical significance was evaluated using
      two tailed Pearson test. RESULTS: Choline: N Acetyl aspartate (Cho: NAA) and
      Choline: creatinine (Cho: Cr) ratios from MRS as well as Apparent Diffusion
      Coffecient (ADC) values from DWI were significantly higher with increasing
      severity of tumour grade. Accuracy of 58.6% was obtained with DWI while it was
      83% with MRS. MRS and DWI used together provided 88.4% accuracy. All parameters
      evaluated showed statistical significance. CONCLUSION: Both DWI as well as MRS
      were found to have statistically significant roles in grading of glial brain
      tumours. MRS was found to be more useful than DWI.

PMID- 28764262
TI  - Relationship between Automated Coronary Calcium Volumes and a Set of Manual
      Coronary Lumen Volume, Vessel Volume and Atheroma Volume in Japanese Diabetic
      Cohort.
AB  - INTRODUCTION: A high degree of correlation exists between Coronary Artery
      Diseases (CAD) and calcification of the vessel wall. For Percutaneous Coronary
      Interventional (PCI) planning, it is essential to have an exact understanding of
      the extent to which calcium volume is correlated to the lumen, vessel, and
      atheroma volume regions in the coronary artery, which is unclear in recent
      studies. AIM: Four automated Coronary Calcium Volume (aCCV) measurement methods
      {threshold, Fuzzy c-Means (FCM), K-means, and Hidden Markov Random Field (HMRF)}
      and its correlation with three manual (experts) coronary parameters namely:
      Coronary Vessel Volume (mCVV), Coronary Lumen Volume (mCLV), and Coronary
      Atheroma Volume (mCAV), was determined in a Japanese diabetic cohort. MATERIALS
      AND METHODS: Intravascular Ultrasound (IVUS) image dataset from 19 patients
      (around 40,090 frames) was collected using 40 MHz IVUS catheter (Atlantis(r) SR
      Pro, Boston Scientific(r), pullback speed of 0.5 mm/sec). The methodology
      consisted of automatically computing the calcium volume in the entire IVUS
      coronary videos using FCM, K-means, and HMRF based pixel classification and
      comparing it against the previously published threshold-based method. The
      Coefficient of Correlation (CC) was then established between the four aCCV and
      three manually (experts) coronary parameters: mCVV, mCLV, and mCAV computed using
      iMAP software Boston Scientific(r). Statistical tests (Two-tailed paired Student
      t-test, Wilcoxon signed rank test, Mann-Whitney test, Chi-square test, and
      Kolmogorov-Smirnov KS-test) were performed to demonstrate consistency,
      reliability, and accuracy of the proposed work. RESULTS: Correlation coefficient
      of: (a) automated threshold-based volume; (b) automated FCM based volume; (c)
      automated K-means based volume; and (d) automated HMRF based volume and
      corresponding three manually (expert's) coronary parameters (mCLV, mCVV, mCAV)
      were: (0.51, 0.40, 0.48), (0.52, 0.38, 0.49), (0.56, 0.45, 0.52), and (0.57,
      0.42, 0.56), respectively. The CC between age and haemoglobin was 0.50.
      CONCLUSION: Automated coronary volume measurement using HMRF method is more
      accurate compared to threshold, FCM, and K-means-based method, since it is more
      strongly correlated with three expert's readings.

PMID- 28764264
TI  - Atypical Imaging Features of a Simple Intramuscular Lipoma.
AB  - Lipoma is a benign tumour of mesenchymal tissue which closely resembles normal
      fat even histologically but for its biochemical and ultrastructural differences.
      Simple lipoma presents as a mass which resembles fat on all the imaging
      modalities. Atypical lipoma, lipoma variants and liposarcoma show specific
      imaging features. We report this case due to the varied imaging appearance of a
      simple lipoma. A 52-year-old lady presented with history of swelling along the
      anterior aspect of thigh. Sonography, CT and MRI had done which revealed an
      atypical lipoma; however excision biopsy proved to be a simple lipoma.

PMID- 28764263
TI  - Acute Pyelonephritis - Correlation of Clinical Parameter with Radiological
      Imaging Abnormalities.
AB  - INTRODUCTION: Pyelonephritis (PN) is a suppurative infection of the kidney, most
      commonly due to bacterial infection and may be either acute or chronic. Acute PN
      (APN) subdivided into uncomplicated and complicated. Severity of PN cannot be
      assessed by clinical or laboratorial parameters alone, radiological imaging such
      as Ultrasound (USG) abdomen, Computed Tomography (CT) is required to know the
      nature, extent and severity of disease and for planning interventions. AIM: The
      aim of this study was to compare clinical and biochemical parameters with
      radiological findings (USG/CT) among patients diagnosed to have PN. MATERIALS AND
      METHODS: The medical records of all patients admitted with PN at the Institute of
      Nephrourology, Bangalore from January 2016 to December 2016 were reviewed. Their
      clinical and biochemical parameter were compared with radiological findings.
      Statistical analysis was performed with Statistical Package for the Social
      Sciences (SPSS) Version 15.0. RESULTS: There were 100 patients diagnosed with PN
      in the study period. Mean age of patient was 48.7 years and PN was common among
      females (62%). Classical triad of PN was present in 87% of patients. Acute kidney
      injury was present in 47% of patients. Diabetes (69%) was the most common
      comorbid condition. Positive urine culture was found in 24% of patients. USG
      abdomen was performed in all patients and it was suggestive of APN in 66% cases.
      CT abdomen was available for 74% and it revealed PN in 70%, of patients. Among
      these Emphysematous PN (EPN) was found in 4% and renal abscess in 3% of patients.
      In this study, USG findings of PN were correlated with triad of PN symptoms and
      those who had PN for the first time. CONCLUSION: In this study, majority of the
      patients presented with clinical triad of PN-fever, flank pain and dysuria. Urine
      culture was positive only in few cases. USG was able to diagnose large number of
      PN cases except emphysematous change and renal abscess which was detected by CT.
      The detection of PN was better with CT when compared to USG.

PMID- 28764265
TI  - Semilobarholoprosencephaly - A Dreading Congenital Anomaly.
AB  - Holoprosencephaly (HPE) is a group of structural abnormalities of brain that is
      an important cause of childhood mortality and morbidity. They usually occur due
      to impaired midline cleavage of embryonic forebrain i.e., failure of
      differentiation of the prosencephalon into the telecephalon and diencephalon. De
      Myer classified this anomaly ranging from alobar to semilobar and lobar type. It
      can be associated with microcephaly and midline facial anomalies. We present a
      case of semilobar holoprosencephaly with corpus callosal agenesis.

PMID- 28764266
TI  - MRI findings of Persistent Mullerian Duct Syndrome: A Rare Case Report.
AB  - Embryologically mullerian duct derivatives lead to formation of female genitalia
      and wolffian duct derivatives to male genitalia. Presence of mullerian duct
      derivatives in a chromosomally normal male (XY) leads to male
      pseudohermaphroditism and is referred to as Persistent Mullerian Duct Syndrome
      (PMDS). A young male patient with bilateral cryptorchidism presented to our
      hospital who was subsequently imaged. There are many case reports of persistent
      mullerian duct syndrome but they focus mainly on surgical aspects. In this
      article, MRI features of persistent mullerian duct syndrome are presented.

PMID- 28764267
TI  - Pneumatosis Cystoides Intestinalis.

PMID- 28764268
TI  - Comparison between Two Endotracheal Tube Cuff Inflation Methods; Just-Seal Vs.
      Stethoscope-Guided.
AB  - INTRODUCTION: The Endotracheal Tube (ETT) cuff performs a critical function of
      sealing the airway during positive pressure ventilation. There is a narrow range
      of cuff pressure required to maintain a functionally safe seal without exceeding
      capillary blood pressure. AIM: We aimed to compare Just-Seal (JS) and Stethoscope
      Guided (SG) method of ETT cuff inflation with respect to the volume of air
      required to inflate the cuff, the manometric cuff pressure achieved and also to
      assess for the occurrence of postoperative sore throat after extubation in both
      the groups. MATERIALS AND METHODS: It was a prospective observational study done
      in a Tertiary Teaching Public Hospital over a period of 11/2 years on 100
      patients with 50 each in two groups; JS or SG method of cuff inflation. SPSS
      Version 17 was used for data analysis. RESULTS: Statistically significant
      difference (p-value of less than 0.05) was noted between the two methods based on
      the volume of air injected into the cuff {the mean volume injected in JS was 6.79
      ml and in the SG was 4.95 ml with p=5.71E-16 (< 0.05)} and cuff pressure achieved
      {mean cuff pressure achieved was 38.80 cm H2O in the JS and 29.64 cm H2O in SG
      with p=2.29E-14 (< 0.05)}. The incidence of post extubation sore throat was 54%
      (27 in 50) in the JS group and only 12% (6 in 50) in the SG; p= 0.00000797.
      CONCLUSION: ETT cuff inflation guided by a stethoscope is an effective technique
      for ensuring appropriate cuff pressures thus accomplishing the objective of
      providing safe and superior quality care of the patient both during and after
      anaesthesia and reducing the likelihood of even minimal risk complications that
      may still have legal implications.

PMID- 28764269
TI  - Analysis of Clinical Indicators of Quality in Patients with Endotracheal
      intubation.
AB  - INTRODUCTION: Quality and safety in anaesthesia is usually monitored by analysis
      of perioperative mortality-morbidity and are influenced by anaesthetic and non
      anaesthetic factors. AIM: This study was conducted to analyse the incidence of
      clinical indicators of quality in endotracheally intubated patients undergoing
      general abdominal surgeries and obstetric and gynaecological procedures under
      general anaesthesia and to determine contributing factors for the same. MATERIALS
      AND METHODS: This retrospective study was conducted at our institute over a
      period of 12 months and 709 case records of patients were reviewed. Patients aged
      14 years and more belonging to all ASA groups undergoing abdominal surgeries for
      general and obstetric and gynaecological causes under General Anaesthesia (GA)
      with endotracheal intubation posted for both elective and emergency surgeries
      were included in the study. Demographic details including name, age, sex,
      hospital number, height, weight, body mass index, type of surgery, nature of
      surgery, duration, American Society of Anaesthesiologists (ASA) physical status
      were recorded and presence or absence of clinical indicators of quality (presence
      of cannot intubate cannot ventilate scenario, occurrence of dental injury,
      episode of non cardiogenic pulmonary oedema, incidents of residual neuromuscular
      blockade, existence of aspiration pneumonia, unplanned ICU/HDU admissions,
      interventions for respiratory/ cardiac arrest, occasions of respiratory distress
      in the recovery period, occurrence of respiratory arrest within 48 hours and re
      intubation) were noted and analysed for all 709 patients. RESULTS: Total 709
      patients were analysed in our study. We found that incidence of ICU admission was
      1.83% and that of respiratory distress which needed intervention were 0.56%. A
      total of 0.28% patients needed reintubation. Residual neuromuscular blockade was
      seen in 0.28% patients. We did not find any case of respiratory and cardiac
      arrest and also there was no Cannot Ventilate and Cannot Intubate (CVCI)
      situation encountered in our study. SPSS for windows (version 17.0) was used as
      statistical software. Chi-square test was the statistical test for significance.
      A p-value < 0.05 was considered significant. CONCLUSION: Proper optimization of
      patients prior to surgery and optimal perioperative care will result in better
      quality of care and safety in anaesthesia. Documentation of events and its
      management during perioperative period will help to know the fields of
      inappropriate management and thereby improve the quality of care and detect the
      incidence rates with accuracy and help to formulate protocol for institution.

PMID- 28764270
TI  - Feasibility and Complications of Spinal Anaesthesia in Percutaneous
      Nephrolithotomy: Our Experience.
AB  - INTRODUCTION: Percutaneous Nephrolithotomy (PCNL) is the treatment modality used
      for the extraction of large renal stones, or multiple calculi or stones resistant
      to shock wave lithotripsy. The General Anaesthesia (GA) is the standard modality
      for PCNL. However, few studies conclude that Spinal Anaesthesia (SA) can be an
      alternative method of anaesthesia with similar incidence of complications. AIM:
      In our study we evaluated the feasibility of spinal anaesthesia in terms of
      intraoperative and postoperative results in patients undergoing PCNL. MATERIALS
      AND METHODS: The total 1298 PCNL operations were done for kidney stone from
      January 2013 to December 2016, out of which 1160 patients underwent PCNL under SA
      while remaining 138 operations were carried out under GA in the prone position.
      We retrospectively collected data from the patient's documents. The
      intraoperative haemodynamic stability was primary objective, and average fall of
      haemoglobin, postoperative anaesthetic outcome like total tramadol used in first
      24 hours, surgical outcome like total clearance of stone burden, patient
      satisfaction, surgeon satisfaction, need of blood transfusion, conversion to
      general anaesthesia and pleural puncture were the secondary objectives. RESULTS:
      The mean age of the patients was 38.0+/-17.1 years, and the mean operative time
      was 80.0+/-25.9 minutes. The mean calculus size was 30.2+/-11.8 mm. Return of
      sensory and motor activity in our study was 150.0+/-29.2 minutes and 111.0+/-18.8
      minutes, respectively. In first 10 minutes of anaesthesia, 148 (12.75%) patients
      developed hypotension, which was managed by ephedrine 6 mg intravenously (IV).
      Total seventy two patients (6.2%) needed blood transfusion and 32 (2.75%)
      complained of headache, dizziness and low back pain for two to four days after
      the operation, which improved with analgesics and bed rest. Ninety percent of the
      patients had complete clearance of calculus or there were no significant residual
      calculi larger than 5 mm on follow up ultrasonography. CONCLUSION: It can be
      concluded from our study that spinal anaesthesia is the safe and effective method
      of anaesthesia for PCNL in adult patients.

PMID- 28764271
TI  - An Experience: An Oropharyngeal Airway with an Unique Feature.

PMID- 28764272
TI  - The Effect of Individual Factors, Socioeconomic and Social Participation on
      Individual Happiness: A Cross-Sectional Study.
AB  - INTRODUCTION: Happiness and exhilaration are the most essential demands of human
      innate psychological needs that affect both physical and mental health. AIM: The
      present study aimed to investigate the effect of individual factors,
      socioeconomic and social participation on individual happiness. MATERIALS AND
      METHODS: In this study, we evaluated 15 to 54-year-old individuals to find the
      effects of individual factors, socioeconomic and social partnership (formal or
      informal) on human happiness. A random sampling method was used in the present
      study. The Oxford Happiness Questionnaire (OHQ) was used. Data analysis was
      performed using descriptive statistics including; frequency, percentage, Mean+/
      SD. Correlation coefficient, one way ANOVA and logistic regression were also used
      as analytical statistics. RESULTS: There was a significant relationship between
      gender (p=0.001, r=0.144), marital status (p=0.001, r=0.174), happy parents
      (p=0.001, r=0.194), educational grade (p=0.001, r=0.189), employment status
      (p=0.001, r=0.180), income (p=0.001, r=0.264), car ownership (p=0.001, r=0.173),
      informal social participation (p=0.001, r=0.3) and formal social participation
      (p=0.001, r=0.231) with happiness. However, the relationship between home
      ownership (p=0.346, r=-0.015), and happiness was not significant. CONCLUSION: It
      seems that good and cordial relations with others, including family, relatives
      and friends (informal social participation) are the main sources and the most
      important factors of life satisfaction and human happiness. Higher income can
      increase happiness by enhancing the possibility to access the needs, desires,
      problems solving, enhancing the social support and self esteem and opportunities
      to perform one's favourite activities.

PMID- 28764273
TI  - Prevalence of Metabolic Syndrome among Psychiatric Inpatients: A Hospital Based
      Study from Kashmir.
AB  - INTRODUCTION: Over the last fifty years there has been dramatic change in the
      human environment, behaviours and way-of-life. These changes have resulted in
      escalating rates of metabolic syndrome not only in general population but also
      among people with mental illness. Various factors, like the lack of exercise, use
      of psychotropic medications and inadequate medical care leads to the increased
      risk of metabolic changes among people with mental illness. Hence, there is a
      greater need to evaluate metabolic syndrome in this population. AIM: To find the
      prevalence of metabolic syndrome among psychiatric inpatients in Tertiary Care
      Hospital in Kashmir region of North India. MATERIALS AND METHODS: It was a cross
      sectional study conducted at the Institute of Mental Health and Neurosciences,
      Kashmir, India. A total of 213 in-patients with a primary psychiatric diagnosis
      as per The International Classification of Diseases, Tenth Revision (ICD 10)
      Classification of Mental and Behavioural Disorders criteria were evaluated for
      the presence of metabolic syndrome. A modified National Cholesterol Education
      Program Adult Treatment Panel III (NCEP ATP III) criterion for the diagnosis of
      metabolic syndrome was used. All the intergroup comparisons for parametric data
      were done by Student's t-test, whereas non-parametric data were analysed by Chi
      square tests. A p-value <0.05 was considered statistically significant. RESULTS:
      The overall prevalence of metabolic syndrome was 34.74%. The prevalence was
      higher in females (43.3%) than males (28.5%) (p<0.05) and it increased with age,
      with the highest prevalence in the age group >50 years (p<0.05). Among the
      diagnostic subgroups, the prevalence was highest among patients with unipolar
      depression (45.0%), while it was lesser in patients with bipolar disorders
      (37.88%) and psychotic disorders (30.95%). Prevalence of metabolic syndrome was
      significantly higher (63.64%) among patients taking second generation
      antipsychotics (p<0.05). CONCLUSION: Our study shows that metabolic syndrome is
      highly prevalent among psychiatric inpatients and needs to be addressed to
      prevent the risk for cardiovascular diseases.

PMID- 28764274
TI  - Comparison of Neurological Soft Signs between Psychotic and Non Psychotic
      Patients.
AB  - INTRODUCTION: Neurological Soft Signs (NSS) are a group of non-specific signs
      manifested in some psychiatric patients. Till date, most studies have focused on
      NSS in schizophrenic patients. AIM: In the current study, the mean NSS score was
      compared between psychotic and non psychotic patients. MATERIALS AND METHODS:
      This descriptive analytical study was conducted on 96 hospitalized patients
      having psychotic disorders. The patients were first examined by a psychiatrist
      and their axis I diagnoses (according to DSM-IV-TR) were made. Accordingly, the
      patients were divided into three groups of psychotic (schizophrenic and
      schizoaffective) and bipolar disorder patients with and without psychotic
      symptoms. Using a 28-item questionnaire, the patients were neurologically
      examined and their NNS scores were calculated. The mean scores were compared
      among the groups. RESULTS: Based on the results, the mean NSS score in psychotic
      patients (schizophrenic and schizoaffective) was higher as compared to that in
      non-psychotic patients (bipolar disorder patients without psychotic symptoms) and
      this difference was statistically significant (p<0.0001). CONCLUSION: It seems
      that calculation of NSS score in psychotic patients can help predict the response
      to pharmaceutical treatment, risk of drug reactions/side effects and prognosis of
      disease. Drawing a definite conclusion in this regard requires further
      investigations.

PMID- 28764275
TI  - Study of Association of Substance Use Disorders with Family Members'
      Psychological Disorders.
AB  - INTRODUCTION: Substance Use Disorders (SUDs) represents a serious problem in
      Iranian community that may lead to psychological disorders in families. AIM: This
      study was conducted to investigate the association of SUDs with family members'
      psychological disorders. MATERIALS AND METHODS: The sample size of the study
      consisted of 724 people referred to a counseling and psychology clinic in
      Shahrekord, southwest Iran. For data gathering, random method was adopted. After
      the relationship was established with the patients during the counseling and
      their confidence was gained, development of SUDs and related effect on the
      referred patient's family members were investigated by a pre-developed checklist.
      The statistical tests used to analyse the data were chi-square, Fisher's exact
      test, and odds ratio. RESULTS: The most frequent disorder noted was depression
      (40.5%) followed by generalized anxiety disorder (21%), minor interpersonal and
      children's behavioural problems (15%), and hysteria (8%). Depression, hysteria,
      and minor interpersonal and children's behavioural problems in the women and men
      were reported 48% vs. 20%, 9% vs. 5%, and 10% vs. 27%, respectively. A
      significant association was seen between SUDs in the patients' spouses and
      children as well as in their families, and gender, marital status, and
      occupation, but not place of residence and education. CONCLUSION: An association
      was seen between the psychiatric disorders in the people referring the studied
      center and SUDs in their families. Addiction in family plays an important role in
      developing or recurring psychiatric disorders in other family members.

PMID- 28764276
TI  - Can Unilateral Pityriasis Rosea be Considered a Form of Superimposed Lateralized
      Exanthem?

PMID- 28764277
TI  - Evaluation of the Efficacy of Clinical Breast Examination Gloves in the Diagnosis
      of Breast Lumps.
AB  - INTRODUCTION: Recent studies have questioned the efficacy of mammography in
      reducing breast cancer-related mortality. Additionally, the efficacies of
      commercially available gloves marketed as aiding the detection of breast lumps
      have not been independently verified. AIM: To evaluate the efficacy of clinical
      breast examination gloves in the detection of breast lumps. MATERIALS AND
      METHODS: During the period from October 2011 to June 2012, patients were
      submitted to clinical examination with and without gloves. This prospective study
      involved 202 patients who underwent conventional clinical breast examination
      (test 1) or clinical breast examination with Sensifemme(r) gloves (test 2). All
      patients underwent subsequent bilateral ultrasonography (test 3) to confirm the
      findings of the physical examinations. The Chi-square test was used to compare
      values, while the kappa concordance index was used to determine the concordance
      between the diagnostic tests. RESULTS: The mean age of the patients was 43 years;
      298 breast lumps were detected. In the clinical examination group (test 1),
      sensitivity was 54%, specificity was 78%, and accuracy was 57%. These rates for
      clinical breast examinations with gloves (test 2) were 68%, 58%, and 66%,
      respectively. The glove increased the diagnosis of breast nodules by 14%; the
      rate of false-positives was also higher (42% for test 2 compared to 22% for test
      1). The accuracy of the glove was found to be superior to clinical examination
      after 100 patients had been examined. The kappa indices for test 1 vs. test 3 and
      for test 2 vs. test 3 were 0.15 and 0.16, respectively. CONCLUSION: Clinical
      examination using the glove was more effective than clinical examination with
      bare hands for the diagnosis of breast lumps, as it increased the sensitivity and
      accuracy of lump detection. However, this was at the expense of a higher false
      positive rate, which can lead to further tests, unnecessary biopsies, and patient
      anxiety. The concordance of clinical examination results (whether performed with
      or without the glove) with those of ultrasonography is weak. Moreover, the glove
      has a steep learning curve that may discourage its use in certain circumstances.

PMID- 28764278
TI  - Comparison of Polymerase Chain Reaction and Immunohistochemistry Assays for
      Analysing Human Papillomavirus Infection in Oral Squamous Cell Carcinoma.
AB  - INTRODUCTION: Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC) are
      two well-known techniques used for the diagnoses of genetic diseases, tumours and
      different pathogens. PCR basically amplify regions of DNA within a single
      molecule which may have etiologic significance, it is a method for in vitro
      amplification of specific DNA or RNA sequences, whereas IHC is used to verify
      tissue constituents (the antigens) with the utilization of specific antibodies
      that can be visualized through staining. AIM: To compare and analyse PCR and IHC
      for their sensitivity to detect Human Papillomavirus (HPV) in Oral Squamous Cell
      Carcinoma (OSCC). MATERIALS AND METHODS: This study was based on samples
      retrospectively collected from 47 patients with primary OSCC who were diagnosed
      and treated at The Aga Khan University Hospital, Karachi, Pakistan, during the
      period of January 2010 to December 2013. Inclusion criteria were complete
      clinicopathologic data, adequate clinical follow up and availability of
      sufficient paraffin- embedded tumour material. HPV general and type specific 16
      and 18 were investigated by means of PCR. HPV immunoreactivity was further
      investigated by means of IHC. RESULTS: Among the 47 evaluated patients, 32
      (68.1%) were male and 15 (31.9%) were female, PCR detected the presence of HPV in
      32 (68.1%) patients while IHC showed no positive test results. p53 was positive
      in 32 (68.1%) patients and negative in 15 (31.9%). HPV type 16 being most
      prevalent showing positivity in 27 (57.4%) patients whereas, type 18 was positive
      in only 1 (2.1%) patient. CONCLUSION: We concluded that PCR is more sensitive and
      reliable when diagnosing and detecting HPV for OSCC rather than IHC as results
      from IHC were all negative and insignificant, hence PCR should be the first
      initial diagnostic test for detecting HPV due to its better sensitivity and
      successful detection of HPV.

PMID- 28764279
TI  - To Evaluate the Effectiveness of TBTS - A Novel Device to do Self-Stretching of
      Gastroc-Soleus Muscle in Patients with Equinus Deformity.
AB  - INTRODUCTION: Various methods have been used for management of equinus deformity.
      However, stretching gastroc-soleus muscle and achilles tendon is a difficult
      task. It is labour intensive, which makes the provision of treatment difficult
      for many patients. AIM: To study the effectiveness of Tension Bar Tendon Stretch
      (TBTS) compared to conventional stretching in patients with equinus deformity in
      terms of improvement in equinus angle and spasticity. MATERIALS AND METHODS: A
      prospective randomised case control study was done on 16 patients of both the
      sexes in the age group four years to 56 years. Patients were stratified based on
      presence or absence of spasticity. Patients were further randomly allotted to the
      study or control group. Study group received stretching with TBTS in addition to
      the conventional rehabilitation programme. Patients were assessed in terms of
      improvement in equinus deformity and spasticity (modified Ashworth scale). These
      indices were measured at 0 month (pre-treatment), 1 month (post-treatment), and 6
      months (follow up). RESULTS: Equinus deformity in patients with spastic equinus
      changed from 22.4 degrees  to 12 degrees  in study group while in control group
      change was from 21 degrees  to 17 degrees . The difference was statistically
      significant with p-value of 0.001. Non-spastic (post accidental) changed from 30
      degrees  to 15 degrees  in study group while in control group change was from 31
      degrees  to 23 degrees  with p-value of 0.001. Modified Ashworth Score (MAS) was
      assessed only in spastic equinus, while in study group MAS changed from 2.8 to
      1.5 and MAS change was 2.6 to 2 in control group; this difference after six
      months of therapy was statistically significant with a p-value of 0.001.
      CONCLUSION: TBTS can be an effective tool in rehabilitation of patients having
      equinus deformity; it provides an effective and patient controlled stretching and
      no need for a physical therapist. TBTS is a novel but simple instrument that can
      be made locally by the patient or the family.

PMID- 28764280
TI  - Content Validation of Total Knee Replacement Rehabilitation Protocol in Indian
      Population.
AB  - INTRODUCTION: Total knee replacement (TKR) surgery has become the most successful
      surgery for patients with severe debilitating arthritis. The guidelines for
      rehabilitation progression should be tailored respecting the tissue healing
      parameters. Hence, the current literature states a need for protocol to mitigate
      these impairments and ultimately result in improved functional outcomes.
      OBJECTIVE: The present study aimed to validate the content of TKR rehabilitation
      protocol in Indian population. MATERIALS AND METHODS: The process of content
      validation involves development stage and expert judgment stage. The protocol was
      designed into three stages with extensive review of literature. After designing
      the protocol, nine experts in field of musculoskeletal Physiotherapy performed
      the judgemental process. The process of validation includes rating of experts in
      a 5 point likert grading on two parameters namely relevance and ease of
      performance. Based on expert's inputs on TKR protocol, the level of agreement,
      content validation index and kappa value was calculated. RESULTS: The three
      staged TKR protocol almost exhibited an excellent agreement on all stages.
      However, muscle activation exercises (except Vastus medialis obliques
      activation), stretching, strengthening program and functional training showed
      100% agreement than other stages. CONCLUSION: The structured TKR protocol
      exhibited excellent content validity to its use in Indian population.

PMID- 28764281
TI  - Immediate Effects of Paraspinal Dry Needling in Patients with Acute Facet Joint
      Lock Induced Wry Neck.
AB  - INTRODUCTION: Acute facet joint lock induced wry neck (AFJL-WN) is common among
      adult population and it is primarily managed by medications and physiotherapy.
      However, the immediate recovery from pain and movements restriction caused by
      AFJL-WN is not documented in favour of existing interventions. AIM: To evaluate
      the immediate effects of paraspinal dry needling (PSDN) on acute neck pain and
      movement deficit in patients with AFJL-WN. MATERIALS AND METHODS: A total of 21
      patients with AFJL-WN were treated with single session of PSDN for 12-15 minutes.
      The Visual Analog Scale (0-100mm) and Hand Held Goniometer were used to assess
      the immediate, 24 hours and 1 week follow-up neck pain and cervical spine's range
      of motion respectively. The mean and standard deviation was used to make
      inferences. RESULTS: Immediately after PSDN the pain score was reduced and
      cervical spine range of motion have improved. The 24 hours and 1 week follow-up
      pain and range of motion scores have shown the sustained improvement without
      deteriorations. CONCLUSION: PSDN is effective method to achieve pain free neck
      movements in patients with AFJL-WN.

PMID- 28764282
TI  - Nature's Benefaction as a Life Saver for an Avulsed Tooth: An In vitro Study.
AB  - INTRODUCTION: Dentoalveolar trauma is a very common and avulsion is the most
      frequent injury. Treatment of choice following avulsion is immediate
      reimplantation. However, in cases where this might not be possible the prognosis
      of reimplanted teeth can be improved by the selection of an appropriate storage
      media. Prevention of ankylosis and replacement resorption depends more on the
      potential of storage media to maintain cell viability rather than the
      extraalveolar time period. AIM: To compare and evaluate the efficacy of different
      storage media in maintaining the viability of Periodontal Ligament (PDL) cells in
      an avulsed tooth. MATERIALS AND METHODS: A total of 58 freshly extracted human
      premolar teeth were divided into four experimental groups and two control groups.
      The positive and negative controls corresponded to 0 minute and an eight hours
      dry time, respectively. The experimental teeth were stored dry for 30 minutes and
      then immersed in one of the four media: Hank's Balanced Salt Solution (HBSS),
      coconut water, aloe vera and saline for 45 minutes. The teeth were then treated
      with Collagenase Type II and Dispase for 30 minutes. The number of viable PDL
      cells were counted with a haemocytometer and analysed. The statistical analysis
      was done using SPSS version 15.0. The Analysis of Variance (ANOVA) and Post-hoc
      tests (Tukey-HSD) were performed to reveal the statistical significance. The
      values were represented in number (%) and mean+/-SD. RESULTS: Statistical
      analysis demonstrated that among the experimental groups maximum percentage of
      viable cells were seen in HBSS (87.33%) followed by coconut water (79.87%), aloe
      vera (70.59%) and saline (50.56%). CONCLUSION: Within the parameters of this
      study, it can be concluded that the HBSS is the most effective storage media in
      maintaining the viability of PDL cells. However, in Indian scenario where
      availability of HBSS is questionable, coconut water can be considered as the best
      natural storage media for an avulsed tooth followed by aloe vera.

PMID- 28764283
TI  - Fabrication and Appraisal of Poly (Lactic-Co-Glycolic Acid) - Moxifloxacin
      Nanoparticles using Vitamin E-TPGS: A Potential Intracanal Drug Delivery Agent.
AB  - INTRODUCTION: Nanotechnology is gaining momentum in the search for ideal
      biomaterials by dental researchers. The expansible nature of Endodontology deems
      exploration, learning and scrutinizing newer avenues which have the potential to
      be applied and investigated. The popularity of polymers as drug delivery vehicles
      has opened avenues for their application in the root canal system. This study
      utilized application of biodegradable polymers as potential drug delivery
      vehicles against Enterococcus faecalis, one of the main reasons for post
      treatment disease. AIM: This study aimed at fabricating Poly (Lactic-co-Glycolic
      Acid) (PLGA)-moxifloxacin nanoparticles and assessing its sustained antimicrobial
      efficacy with calcium hydroxide and chitosan-moxifloxacin hydrogel against
      Enterococcus faecalis. MATERIALS AND METHODS: PLGA (50:50) in a quantity of 100
      mg was dissolved in 1 ml ethyl acetate and 45 ml of 0.3% w/v Vitamin-E
      Polyethylene Glycol 1000 Succinate (vitamin E-TPGS) was kept for magnetic
      stirring in separate beaker. Moxifloxacin (50 MUl) was added to polymer PLGA
      following which vitamin E-TPGS was added to the polymer. Nanoparticles were
      fabricated using ultrasonication and collected by centrifugation. Surface
      characterization was assessed using scanning electron microscope. Results were
      obtained in the form of zone of inhibition by the nanoparticles against
      Enterococcus faecalis and comparisons were made with chitosan-moxifloxacin
      hydrogel and calcium hydroxide using Analysis of Variance (ANOVA) followed by
      Student t-test. RESULTS: Upon statistical analysis, the zone of inhibition
      against E. faecalis remained constant with PLGA-moxifloxacin nanoparticles for 14
      days while it decreased with chitosan-moxifloxacin hydrogel and remained nil for
      calcium hydroxide (p<0.01). CONCLUSION: The study posits that PLGA encapsulated
      moxifloxacin nanoparticles showcased sustained antibacterial effect in low doses
      against the test pathogen. Its sustained and programmed release makes them unique
      contenders for further evaluation in Endodontics as potential intracanal
      medicaments.

PMID- 28764284
TI  - Efficacy of Bromelain along with Trypsin, Rutoside Trihydrate Enzymes and
      Diclofenac Sodium Combination Therapy for the treatment of TMJ Osteoarthritis - A
      Randomised Clinical Trial.
AB  - INTRODUCTION: Osteoarthritis (OA) is a degenerative disorder characterized by
      chronic inflammatory response of cartilage and articular surface involving
      Temporomandibular Joint (TMJ). Pain as one of the major symptom of osteoarthritis
      affects the quality of life and is usually managed by Non Steroidal Anti
      Inflammatory Drugs (NSAIDs) such as diclofenac sodium. Bromelain, trypsin and
      rutoside trihydrate formulation can be used to treat this disease because of anti
      inflammatory and anti-oxidant effects. AIM: To assess the effectiveness of oral
      bromelain, trypsin, rutoside trihydrate enzymes and diclofenac sodium combination
      therapy over diclofenac sodium for the treatment of TMJ osteoarthritis. MATERIALS
      AND METHODS: Thirty Patients with symptomatic TMJ osteoarthritis were randomly
      divided into three groups. 10 patients were treated with diclofenac sodium (Group
      1), 10 were given oral enzymes (bromelain, trypsin, rutoside trihydrate) and
      diclofenac sodium combination (Group 2), and 10 were treated with oral enzyme
      preparation (bromelain, trypsin, rutoside trihydrate) (Group 3). Patients were
      evaluated on day 1, day 4, day 7 and day 10. Comparison of pain rating within
      three groups was assessed using numeric rating scale. The efficacy criteria were
      analysed applying ANOVA followed by post-hoc test. RESULTS: Inter group
      comparison of the effectiveness of management of pain, resulted in a value p <
      0.05 between Group 2 and other two groups, which indicated that Group 2 patients
      responded better than Group 1 and Group 3, while p > 0.05 between Group 1 and
      Group 3 showed both groups responded equally to the treatment. CONCLUSION: The
      trial showed significant improvement in reducing pain in patients treated with
      oral enzymes and diclofenac sodium combination therapy.

PMID- 28764285
TI  - A Comparative Evaluation of the Influence of Command Set Methods on Microleakage
      of Glass Ionomer Cement: An In Vitro Study.
AB  - INTRODUCTION: A major challenge when using glass ionomer cement in clinical
      situation particularly in paediatric dentistry is to overcome the problem of
      microleakage. Fast or command setting of Type IX glass ionomer cement using
      external energy source enhances the setting reaction and results in improved
      initial physical and mechanical properties. AIM: To compare and evaluate the
      influence of ultrasonic activation, halogen light irradiation and combined effect
      of both on microleakage of enamel adjacent to Type IX glass ionomer restorations.
      MATERIALS AND METHODS: For forty premolar teeth, standard Class V cavities
      prepared were restored with GC Gold Label Type IX glass ionomer cement in vitro.
      The specimens were randomly divided into four groups: 1) Control group; 2)
      halogen group; 3) ultrasonic group; 4) ultrasonic with halogen group. The teeth
      were kept in distilled water for 24 hours. Teeth were exposed to 1500
      thermocycles at temperature of 12 degrees C +/-2 and 60 degrees C +/-2 with
      alternate immersion in hot and cold water for one minute. First teeth were
      immersed in dye solution for four hours and then in developing solution for four
      hours. The samples were sectioned buccolingually through centre of the
      restorations and degree of dye penetration was assessed under stereomicroscope
      and scored. One-Way ANOVA model was constructed followed by post-hoc Tukey's test
      for multiple pair wise comparison of mean values. RESULTS: Statistically
      significant differences were found in microleakage among the four groups
      (p<0.001) with respect to dye penetration. Halogen group showed least
      microleakage followed by control but differences between them were statistically
      not significant (p>0.05). Similarly the differences between Ultrasonic plus
      halogen group and ultrasonic group were not significant (p>0.05). The differences
      between ultrasonic and halogen group were statistically significant (p<0.05).
      CONCLUSION: Halogen light decreases the microleakage of enamel adjacent to GC
      Type IX glass ionomer restorations, when used to accelerate the setting reaction
      of glass ionomers and can be used as command set method in paediatric dentistry.

PMID- 28764286
TI  - Applicability of Tanaka Jhonston Method and Prediction of Mesiodistal Width of
      Canines and Premolars in Children.
AB  - INTRODUCTION: Essential part of diagnostic procedures in mixed dentition analysis
      is to determine adequate space available for the erupting permanent teeth.
      Various methods of analysis for mixed dentition are available; among them Tanaka
      Johnston method of space analysis for children was developed for North American
      children and is widely used. Its reliability among different racial and ethnic
      groups is yet to be determined. AIM: To check the applicability of Tanaka
      Jhonston method and to derive the mesiodistal width of unerupted canines and
      premolars and also derive new regression equations for Bangalore population.
      MATERIALS AND METHODS: Considering the selection criteria, 400 subjects of
      Bangalore aged 13-16 years were randomly selected and study models were prepared.
      Mesiodistal widths of permanent lower incisors, canines and premolars were
      measured. Estimated width of upper, lower canines and premolars were also derived
      using Tanaka Jhonston method. Data was utilized to predict mesiodistal widths of
      erupting permanent canines and premolars. Descriptive analysis, independent
      student t-test, correlation and regression analysis were carried out. RESULTS:
      Measured and estimated widths of upper and lower canines and premolars were
      compared and the results showed that estimated widths of upper and lower canines
      and premolars over estimated as to the actual measurements. A new regression
      equation was developed by using the formula Y=a+b(X) where Y= predicted width of
      canine and premolars, "a" and "b" are the constants and X= lower incisal width.
      Regression equations for males and females were derived separately. CONCLUSION:
      The original Tanaka Jhonston method over estimated for local Bangalore
      population. New regression equations and prediction tables were derived for males
      and females separately, which should be more conveniently used chairside by the
      clinician.

PMID- 28764287
TI  - Aloe vera for Dry Mouth Denture Patients - Palliative Therapy.
AB  - INTRODUCTION: Xerostomia (dry mouth) is dryness of the mouth which is due to
      reduced salivary flow. Lack of adequate saliva causes discomfort in denture
      wearing patients and decreases retention of dentures. The ability of saliva to
      wet the tissue surface is one of the most important properties for oral comfort
      and retention of complete denture in dry mouth patients. AIM: This study was
      conducted to evaluate and compare the wetting ability of therapeutic Aloe vera
      saliva substitute and commercially available Aqwet saliva substitute on heat
      polymerized acrylic resin. Contact angle of liquid saliva substitute was
      considered as an indicator of wettability. MATERIALS AND METHODS: Aloe vera
      liquid (Aloe vera - Group I) and Aqwet saliva substitute (Aqwet - Group II) were
      compared in terms of their wetting ability. Forty samples of heat-polymerized
      acrylic resin were fabricated and divided into two groups with 20 samples in
      each. Advancing, receding contact angles and angle of hysteresis were measured
      using contact angle goniometer and DSA4 software analysis. Mann-Whitney U test
      was applied for statistical analysis of the study. RESULTS: The mean advancing
      angle and receding angle of Group I (Aloe vera) was smaller than Group II
      (Aqwet). Mean angle of hysteresis of Group I (Aloe vera) was higher than Group II
      (Aqwet). Mann-Whitney U test revealed that there is no significant difference in
      contact angles between the two groups. CONCLUSION: Wetting ability of Group I
      (Aloe vera) saliva substitute was found to be better compared to Group II (Aqwet)
      on heat-polymerized acrylic resin.

PMID- 28764288
TI  - Evaluating the Marginal Integrity of Bulk Fill Fibre Reinforced Composites in Bio
      mimetically Restored Tooth.
AB  - INTRODUCTION: Over the past years, composites in aesthetic dentistry are showing
      a considerable progress, but mechanical strength and polymerization shrinkage are
      the two main drawbacks, which limit their use in high stress bearing areas. AIM:
      To evaluate the marginal integrity of short glass fibre reinforced composite
      restorations, fibre reinforced composites with composite superficial layer, and
      fibre reinforced composites with underlying flowable composite layer. MATERIALS
      AND METHODS: This study was done on twenty eight sound premolar teeth with
      standardized class V cavities restored under four groups as Group I: Particulate
      filler composite (Filtek Z 250 XT, 3M ESPE); Group II: Short glass fibre
      reinforced composite (everX Posterior, GC); Group III: Short glass fibre
      reinforced composite with an overlying layer of particulate filler composite;
      Group IV: Short glass fibre reinforced composite with an underlying layer of
      flowable composite (Filtek Z 250 XT, 3M ESPE). Test samples were immersed in a 2%
      methylene blue dye for 24 hours at 37 degrees C and each tooth was sectioned
      bucco-lingually. Staining along the tooth restoration interface was recorded and
      results were analysed statistically using Independent sample t-test and Tukey's
      post-hoc one-way ANOVA. RESULTS: The results showed significant difference in the
      dye penetration between the restorative materials in the occlusal and gingival
      margins (p=0.02). Short fibre reinforced composites showed a statistically
      significant difference in the microleakage scores when compared with the
      particulate filler composites (p=0.01). CONCLUSION: Short glass fibre reinforced
      composite restorations showed an improved marginal integrity when compared to the
      traditional particulate filler composite restorations.

PMID- 28764289
TI  - Evaluation of Donor Site Morbidity Associated with Iliac Crest Bone Harvest in
      Oral and Maxillofacial, Reconstructive Surgery.
AB  - INTRODUCTION: Iliac crest is the most common donor site for autogenous bone
      grafting as cortical bone, cancellous bone or combination of both can be
      harvested in abundance depending upon the need. Ilium provides highest
      concentration of osteo-component cells and greater quality of bone with less
      morbidity. AIM: The study was conducted to evaluate the donor site morbidity
      associated with autogenous iliac crest bone grafting for reconstruction in
      maxillofacial surgery. MATERIALS AND METHODS: Around 12 patients, who had
      undergone iliac crest bone harvesting for various maxillofacial and
      reconstructive surgical procedures like cleft alveolus repair, malar
      augmentation, mandibular reconstruction following tumour resection and cyst
      enucleation and other surgical procedures performed in the Department of Oral and
      Maxillofacial Surgery, over a span of two years. The donor site was evaluated for
      the following factors: pain, neuropraxia, abnormal gait and scar evaluation.
      RESULTS: None of the 12 patients had intraoperative complications like
      haemorrhage, damage to the muscles/ligaments, fracture of the ilium and damage to
      the acetabular fossa/femur head. Any major postoperative complications were also
      not recorded. Minor postoperative complications like pain, contour defect,
      walking difficulty were present, which gradually got resolved by the time of
      discharge. CONCLUSION: Anterior iliac crest provides an adequate harvest of
      cancellous, corticocancellous or bicortical grafts for reconstruction of various
      osseous defects in the maxillofacial region with least morbidity and should be
      considered as a major reservoir of bone for bony reconstructive procedures.

PMID- 28764290
TI  - Wheatgrass: Green Blood can Help to Fight Cancer.
AB  - INTRODUCTION: Oral squamous cell carcinoma is the sixth most common cancer
      worldwide and is one of the leading causes of death especially in developing
      countries like India. It is usually managed with the help of chemotherapeutic
      agents that are toxic not only to the tumor cells but also to normal cells in
      many ways. Whereas the traditional herbal medicines which are used from ancient
      days in India are generally known to be free of toxic effects and are effective.
      Wheatgrass is the young grass of the wheat plant 'Tritcumaestivum Linn', family
      Poaceae (Gramineae). It contains a number of vitamins, mineral, amino acids and
      vital enzymes, these play an important role in the anticancer approach of this
      herbal product. It is also called as 'green blood' because of its high content of
      chlorophyll, which bears a structural similarity to haemoglobin and this result
      in high oxygen supply to all the body tissues. AIM: To analyse the effect of the
      aqueous wheat grass extract on Oral Squamous Cell Carcinoma (OSCC) cell line by
      MTT assay. MATERIALS AND METHODS: 'KB cell line' (Mouth Epidermal Carcinoma
      Cells) was used for the present study. Aqueous extract of wheat grass was
      prepared in the institution. The aim of the study was to assess the effect of the
      aqueous wheat grass extract on KB cell line(OSCC) by MTT assay. RESULTS: A 41.4%
      of OSCC cell inhibition was observed at 1000 ug/ml dilution of aqueous wheatgrass
      extract in 24 hours. CONCLUSION: The aqueous extract of wheatgrass has an
      inhibitory effect on the oral cancer cell line proliferation.

PMID- 28764291
TI  - Impact of Alcohol Dependency on Oral Health - A Cross-sectional Comparative
      Study.
AB  - INTRODUCTION: Alcoholism is a chronic and progressive psychiatric illness
      characterised by a loss of control over alcohol consumption. Consumption of
      alcohol inevitably affects the oral cavity, oral mucosa and teeth. Literature
      indicates that alcohol dependents may have increased risk of dental caries,
      probing pocket depth and mucosal lesions. AIM: To assess the impact of alcohol
      dependency on oral health status among alcoholics in comparison with non
      alcoholics. MATERIALS AND METHODS: A total 76 alcoholic patients visiting
      Psychiatric Department were compared with matched non alcoholics. Subjects were
      categorised as alcohol dependents based on American Psychiatric Association
      Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic
      criteria. Non alcoholic subjects were selected by controlling for potentially
      confounding variables such as for cigarette, smoking and age. Data was collected
      by interview and clinical examination. Oral health status of subjects was
      assessed using a modified WHO proforma and salivary pH and plaque pH were
      assessed. Chi-square test was used for assessing socio demographic details and
      Mann-whitney U test was used for prevalence of dental caries and periodontal
      diseases, Unpaired t-test was used for plaque and salivary pH. RESULTS: There was
      no statistically significant difference noted among alcoholic and nonalcoholic
      control group with respect to socio demographic details. Prevalence of dental
      caries was higher in alcohol dependent subjects with a mean DMFT of 5.92 compared
      to nonalcoholic subjects (4.51). Prevalence of periodontitis was higher (89.61%)
      in alcohol dependent subjects compared to controls (78.67%). Prevalence of
      mucosal lesions among alcohol dependent subjects was 31.5% which was higher than
      the controls (25%). Subjects who were categorised as alcoholics showed a lower
      plaque and salivary pH compared to non alcoholics. CONCLUSION: Subjects
      categorised as alcohol dependent subjects had slightly lower mean plaque and
      salivary pH and a higher prevalence of dental caries, periodontitis and mucosal
      lesions compared with non alcoholic subjects.

PMID- 28764292
TI  - Focal Adhesion Kinase Expression in Ameloblastoma: A Preliminary Observational
      Study.
AB  - INTRODUCTION: Focal Adhesion Kinase (FAK) is a membrane-associated molecule,
      which plays a major role in tumourigenesis by promoting cell survival,
      proliferation, migration, and invasion. Hence, FAK is a well known molecule that
      has been targeted therapeutically for the treatment of various malignancies.
      Ameloblastoma (AB) is a locally invasive, destructive and recurrent benign
      odontogenic lesion. Based on these properties, we have hypothesized that
      odontogenic epithelium of AB could show increased expression of FAK. AIM: To
      study the expression of FAK in odontogenic epithelium of AB using
      immunohistochemistry. MATERIALS AND METHODS: Thirty four paraffin embedded AB and
      17 Dental Follicle (DF) tissues were retrieved from archives. Immunohistochemical
      staining was performed using FAK antibody on 5 MUm thick formalin fixed paraffin
      embedded sections. The expression of FAK was studied in ameloblast like cells and
      stellate reticulum-like cells and was graded as negative, weak and strong. The
      data was analysed using chi-square test and Fisher's-exact test. RESULTS: In AB,
      both ameloblast like and stellate reticulum like cells showed positive expression
      of FAK in the cytoplasm in all the cases (34). The epithelial islands from all
      the DFs (17) were negative for FAK expression. The difference in the expression
      of FAK in ameloblast like and stellate reticulum like cells was statistically
      significant (p<0.0001). Statistically significant difference was observed in the
      expression of FAK in stellate reticulum like cells of AB and odontogenic
      epithelial islands of DF (p = 0.0017). All the AB cases showed strong expression
      of FAK in ameloblast like cells and negative expression was seen in all the cases
      of DF. CONCLUSION: FAK was strongly expressed in AB as compared to epithelial
      islands of DF. FAK could be responsible for the neoplastic nature of AB and
      possibly play a role in tumour invasiveness.

PMID- 28764293
TI  - The Serological Evidence of Cytomegalovirus Infection as a Potent Aetiological
      Factor for Cleft Lip/Palate, Mental Retardation and Deafness.
AB  - INTRODUCTION: Congenital Cytomegalovirus (CCMV) infection is estimated to occur
      in 0.5% to 2% of all deliveries across the world. According to the available
      literature about Human Cytomegalovirus (HCMV) infected children, 0.5% to 1%
      acquire Cytomegalovirus (CMV) in utero, 40% acquire the infection within the
      first decade of life, between 15% to 70% acquire CMV infection in group day care
      settings and continue to shed the virus for 6 to 48 months after primary
      infection. Although, 90% of the infected infants are clinically asymptomatic at
      birth, shreds of evidence show that these infants are at risk for audiological,
      neurological, and developmental sequelae. Despite this, HCMV still remains
      undetected due to silent or asymptomatic nature of the virus. AIM: The present
      study was aimed to test the hypothesis that HCMV can be a potential aetiologic
      factor in the development of cleft lip/palate, mental retardation and deafness.
      MATERIALS AND METHODS: The study was carried out in a controlled setting under
      strict aseptic conditions. Blood samples were collected from 80 children, who
      were selected strictly adhering to the inclusion criteria and were divided into
      four groups containing 20 children each. Group 1: 20 children with cleft
      lip/palate, Group 2: 20 mentally retarded children, Group 3: 20 completely deaf
      children and Group 4: 20 normal Children (control). The samples were tested for
      HCMV-specific Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies by
      using solid phase enzyme-linked immunosorbent assay and the obtained data were
      analysed statistically using ANOVA and Post-Hoc Tukey's tests. RESULTS: In the
      study group (Group1, 2 and 3) children, the overall positivity for HCMV- specific
      IgG was 100% and 5% borderline to IgM antibodies whereas in the control group
      (Group 4) it was 80% negative to HCMV- specific IgG and 100% negative to IgM
      antibodies. CONCLUSION: From the observations noted in the present study, HCMV
      could be suggested as the potent aetiologic factor in the development of cleft
      lip/palate, mental retardation and deafness.

PMID- 28764294
TI  - Retrospective Study of Root Canal Configurations of Mandibular Third Molars Using
      CBCT- Part-II.
AB  - INTRODUCTION: Abnormal root canal morphologies of third molars can be
      diagnostically and technically challenging during root canal treatment. AIM: The
      aim of this retrospective study was to investigate the root and canal morphology
      of mandibular third molars in Central India population by using Cone Beam
      Computed Tomography (CBCT) analysis. MATERIALS AND METHODS: CBCT images of 171
      mandibular third molars were observed and data regarding number of roots, number
      of canals, Vertucci's classification in each root, prevalence of C shaped canal,
      gender and topographical relation of morphology in mandibular third molar was
      statistically evaluated. RESULTS: Majority of mandibular third molars had two
      roots (84.2%) and three canals (64.3%). Most mesial root had Vertucci Type II
      (55.6%) and Vertucci Type IV (22.2%), distal root had Type I canals (87.5%). Over
      all prevalence of C shaped canals in mandibular third molars was 9.4%.
      CONCLUSION: There was a high prevalence of two rooted mandibular third molars
      with three canals.

PMID- 28764295
TI  - Photographic Assessment of Cephalometric Measurements in Skeletal Class II Cases:
      A Comparative Study.
AB  - INTRODUCTION: Cephalometry has many limitations of which radiation exposure is
      most important. Hence, there is a need to resort to other safer methods which
      could give equal if not better results. AIM: The purpose of this study was to
      compare and correlate the craniofacial measurements obtained from cephalometric
      radiographs and analogous measurements from standardized facial profile
      photographs in skeletal class II cases. MATERIALS AND METHODS: A total of 30
      lateral cephalograms and profile photographs of patients exhibiting skeletal
      class II malocclusion, in the age group of 19-25 years of age, were examined in
      this study using Dolphin software (version 11.8). A standardized protocol was
      followed for all the lateral cephalograms and photographs. A total of 15
      parameters were studied in this study out of which seven were angular and eight
      were linear parameters. Angular parameters included Frankfort Mandibular Plane
      Angle (FMA), Mandibular Plane-Occlusal Plane (MP-OP) angle, Occlusal Plane (OP)
      angle, gonial angle, ANB angle, facial angle and convexity whereas linear
      parameters included Anterior Facial Height (AFH), Ramal height, Posterior Facial
      Height: Anterior Facial Height (PFH/ AFH), convexity (in mm), Nasion
      perpendicular- Point A, Nasion perpendicular- Pogonion, Witts and Mandibular body
      length. All these parameters were digitised on both the cephalogram and
      photographs and were compared using one sample-2 tailed t-test, Pearson
      correlation coefficient. Bland-Altman Plot was considered to find comparison
      between the measurements from photographs and cephalograms in skeletal class II
      patients. RESULTS: On comparing the angular cephalometric and photographic
      variables for the skeletal class II subjects we found the cephalometric
      parameters like FMA, MP-OP angle, OP, gonial angle, convexity (in degrees) to
      have an insignificant difference compared to the analogous photographic
      measurements. On comparing the linear cephalometric and photographic variables,
      it was found that all the cephalometric parameters like AFH, ramal height,
      PFH/AFH, N perp-Point A, N perp-Poghad a good relationship with the analogous
      photographic measurements. CONCLUSION: The photographic method can be considered
      as a repeatable and reproducible method if a homogeneous protocol is followed.
      Thus, photographic measurements may reflect to be a rational and practical
      diagnostic substitute to measurements obtained from cephalograms in Class II
      malocclusion subjects.

PMID- 28764296
TI  - Stereomicroscopic Dye Leakage Measurement of Six Different Root Canal Sealers.
AB  - INTRODUCTION: Hermetic sealing of the root canal is the most desirable outcome of
      any root canal treatment, but almost always the filling of the root canal is
      defective, which is a multifactorial outcome. One such factor majorly influencing
      the obturation is the root canal sealer used. AIM: The present study was done for
      evaluating microleakage in different root canal sealers. MATERIALS AND METHODS:
      Sixty extracted human single rooted teeeth were used in this in-vitro study.
      Sealers tested for microleakage in this study were zinc oxide eugenol based
      sealer, Sealapex, AH Plus, MTA Plus, EndoRez, Endosequence BC. All the specimens
      were examined under stereomicroscope for microleakage and the obtained data were
      statistically analysed using One-way ANOVA test and Tukey's multiple comparision
      tests using the software GraphPad Prism 7.02. RESULTS: The Endosequence BC group
      showed the least dye leakage and the highest leakage was seen in Zinc oxide
      Eugenol based sealer. CONCLUSION: Bio ceramic salers being hydrophilic show
      better sealing ability compared to resin based and eugenol based sealers.

PMID- 28764297
TI  - Comparative Assessment of Conventional Composites and Coloured Compomers in
      Permanent Molars of Children with Mixed Dentition: A Pilot Study.
AB  - INTRODUCTION: Early treatment of carious lesions in children is important for the
      maintenance of oral health. Multicoloured restorations could be the impetus for
      an extremely nervous or defiant child to take dental treatment. AIM: The aim of
      this study was to assess and compare the clinical success of conventional
      composites and coloured compomer material in first permanent molars of children
      with mixed dentition. MATERIALS AND METHODS: A total of sixty sites, divided into
      two groups, with thirty subjects in each group using split mouth design were
      chosen amongst patients reporting to Department of Pedodontics and Preventive
      Dentistry. In control group conventional composites were placed, similarly
      coloured compomers were placed in experimental group under standard operating
      protocol. Patients were recalled for assessment of clinical success amongst
      control as well as experimental group at regular intervals of one; three and six
      months follow up based on Modified Ryge's Criteria. Statistical analysis was done
      using Chi-square test using SPSS version 20.0 (Chicago, USA). RESULTS: Both
      conventional composites and coloured compomers had comparable retention rates in
      terms of anatomical form, marginal integrity, secondary caries and marginal
      discolouration. CONCLUSION: The coloured compomer material showed promising
      results in this six month follow up study in permanent molars and had properties
      comparable to that of conventional composites.

PMID- 28764298
TI  - Index/Ring Finger Ratio, Hand and Foot Index: Gender Estimation Tools.
AB  - INTRODUCTION: Gender estimation from dismembered human body parts and skeletal
      remains in cases of mass disasters, explosions, and assaults cases is an
      imperative element of any medico-legal investigations and has been a major
      challenge for forensic scientists. AIM: The aim of the present study was to
      estimate the gender by using index and ring finger length ratio, hand and foot
      index along with the correlation of both the hand and foot index to determine the
      vital role of all the indices in establishing gender identity. MATERIALS AND
      METHODS: A descriptive cross-sectional study was done on 300 subjects (150 males
      and 150 females). Various anthropometric measurements like hand length, hand
      breadth and hand index, Index Finger Length (IFL), Ring Finger Length (RFL) and
      IFL/RFL ratio as well as foot length, foot breadth and foot index were estimated
      in millimeters (mm) with the help of sliding-anthropometric caliper. The data was
      analysed using independent t-test and Pearson correlation coefficient test. A
      probability value (p) of <= 0.05 was considered statistically significant.
      RESULTS: The index and ring finger ratio was found to be higher in females as
      compared to males. The hand and foot index was more in males than in females. The
      index and ring finger length ratio, hand and foot index between males and females
      was found to be statistically significant for both hands and feet. A
      statistically significant correlation was determined between hand indexes versus
      foot index. CONCLUSION: This study can be useful to establish the gender of a
      dismembered hand or foot when subjected for medicolegal examination.

PMID- 28764300
TI  - Effect of Pranayama on Ppar-gamma, Nf-kappaB Expressions and Red Complex
      Microorganisms in Patients with Chronic Periodontitis - A Clinical Trial.
AB  - INTRODUCTION: Sudarshankriya pranayama is the control of breathing movements to
      regulate the energy flow throughout the body, which has shown to positively
      affect immune function, autonomic nervous system and psychologic-neuro pathways.
      The practice of pranayama has been proven to show several benefits such as
      reduction in stress levels, relieves anxiety and depression, increase in
      antioxidant levels, reduces insulin resistance and improves respiratory function.
      AIM: The objective of the study was to evaluate the levels of Peroxisome
      Proliferator-Activated Receptor Gamma (PPAR-gamma), Nuclear Factor-Kappa B (NF
      kappaB) and the presence of Red Complex Microorganisms (RCM) such as Treponema
      denticola, Porphyromonas gingivalis and Tannerella forsythia in the subgingivalpl
      aque samples of chronic periodontitis subjects before and after intervention with
      pranayama as an adjunct to Scaling and Root Planing (SRP). MATERIALS AND METHODS:
      A total of 30 subjects (control group) were treated with SRP and 30 subjects
      (pranayama group) underwent SRP and pranayama for three months. Probing Pocket
      Depth (PPD), Clinical Attachment Level (CAL), Bleeding Index (BI) and Plaque
      Index (PI) were recorded and the presence of PPAR-gamma, NF-kappaB and RCM were
      assessed at baseline and after three months using polymerase chain reaction.
      ANCOVA test was done to compare the clinical parameters between the groups.
      Fisher's Exact test was done to identify RCM and Mann-Whitney and Wilcoxon-signed
      test was used to identify the expression of NF-kappaB and PPAR-gamma in the
      plaque samples. RESULTS: The change in the mean CAL from baseline to third month
      was significantly higher in pranayama group compared to control group (p<=0.05).
      There was a statistically significant reduction in the expression of NF-kappaB
      and increase in PPAR-gamma expression levels in pranayama group on comparison
      with the control group (p<0.001). The reduction in number of positive samples
      with T.denticola, P.gingivalis and T.forsythia at third month post-intervention
      did not affect the change in the expression levels of NF-kappaB and PPAR-gamma.
      CONCLUSION: The CAL showed significant improvement with reduction in the RCM, NF
      kappaB and increase in PPAR-gamma levels in subjects who underwent pranayama as
      an adjunct to SRP. In future, pranayama can be used as an additional treatment
      modality to provide a new dimension in treatment of periodontitis.

PMID- 28764299
TI  - Assessment of Dental Caries Spectrum among 11 to 14-Year-Old School Going
      Children in India.
AB  - INTRODUCTION: The quantification of dental caries is usually done by DMFT index
      but efforts are being made to find an alternative. Caries Assessment Spectrum and
      Treatment (CAST) is a recent, innovative caries assessment tool which can be used
      in epidemiological surveys. AIM: To assess dental caries using CAST index among
      11-14-year-old school children in Rohtak city, Haryana, India. MATERIALS AND
      METHODS: A cross-sectional study was carried out among 11-14-year-old children in
      schools of Rohtak City using multi stage cluster sampling technique. Rohtak city
      was divided in to nine clusters. In the 2nd stage, one school was randomly
      selected from each cluster with lottery method. Finally from each selected
      school, every odd roll number child between age group 11-14 years, were enrolled
      to reach a sample of 586. Caries was recorded using the CAST index. Each child
      was clinically examined by a trained examiner using CAST index. Descriptive and
      inferential statistics were done and Chi-square test was used to find association
      between caries prevalence and gender. Mann-Whitney U test was used to find any
      difference of mean DMFT between different age groups. RESULTS: A total of 586
      children were examined. Prevalence of dental caries was 28.6%. Highest caries was
      observed in lower right first molar and lower left first molar (13.8% and 11.6%)
      respectively. Pulpal involvement in lower molars was found more than the upper
      molars. CONCLUSION: CAST index presents a simple hierarchical structure of caries
      spectrum and is a promising index for epidemiological studies with complex
      quantifiability.

PMID- 28764301
TI  - Pulpal Response to Ferric Sulfate and Diode Laser When Used as Pulpotomy Agent:
      An In vivo Study.
AB  - INTRODUCTION: Ferric sulfate and Laser has been used for conventional pulpotomy
      therapy. Clinical and radiographic evaluation of pulpotomies using these have
      been done in numerous studies but there exists few studies analysing the
      histologic response of pulp to laser and ferric sulfate. AIM: The aim of the
      study was to evaluate and compare histological changes seen in the pulp following
      ferric sulfate and laser pulpotomy and compare these effects. MATERIALS AND
      METHODS: This was a single blind in vivo study, consisting of 24 primary teeth.
      The teeth were randomly divided into two groups based on the material to be used
      and subgrouped based on the time period (30 and 45 days) of evaluation. The teeth
      were extracted after the study period and tissue processing done and subjected to
      Haematoxylin and Eosin staining procedure. The tissues were evaluated for dentin
      bridge formation, quality of dentin formation in the bridges, location of dentin
      bridges, tissue reaction to the material, inflammatory cell response and
      necrosis. The statistical analysis was done using SPSS 20.0 software. Intragroup
      comparisons of the observed values were analysed using Chi-square test. RESULTS:
      Statistical analysis revealed non-significant difference between the two
      materials to produce reparative dentin and also the quality of dentin bridges
      formed in both the groups during both the observational periods. Majority of the
      samples in both ferric sulfate and laser group exhibited dentin bridge at the
      interface of the exposed pulp, bridging or attempting to bridge the site exposed
      to the pulpotomy material. The ability of the materials to evoke a foreign body
      and inflammatory cell responses in the pulpal tissue was not significant. All the
      samples of both the groups showed signs of necrosis with two samples of laser
      group showing severe necrosis in 45 days period. The difference between the
      groups in 30 days group was statistically significant. CONCLUSION: Laser and
      ferric sulfate are found to be able to initiate dentin bridge at the interface
      between the pulp and the material but the quality of bridge formed was better in
      laser group. Laser group showed more macrophage infiltration, inflammatory cell
      infiltration and areas of necrosis compared to ferric sulfate group though not
      statistically significant.

PMID- 28764302
TI  - Effect of Crown Angulation of Maxillary Incisor on Effective Arch Perimeter.
AB  - INTRODUCTION: It has been postulated that crown angulation and inclination has
      potential space implication within the arch. With the insight of space
      implication of the axial relations of teeth, cases of genuine tooth size
      discrepancies can be dealt with improved stability. AIM: This in vitro study was
      designed to investigate and quantify the influence of angulation and inclination
      of maxillary incisors on the effective arch perimeter. MATERIALS AND METHODS:
      Acrylic teeth were arranged over typhodont frame with spaced maxillary anterior
      segment. Known value of tip and torque in increments were incorporated to
      maxillary incisors through bracket positioning and corresponding consumption of
      the interdental spaces were measured using coordinate measuring machine. RESULTS:
      Study revealed that increase in maxillary incisor crown angulation by 1o results
      in consumption of approximately 0.012 mm of arch perimeter. Similarly, there is a
      consumption of 0.021 mm of arch perimeter with each degree increase in labial
      crown inclination. CONCLUSION: The knowledge of the space implication can be
      included in the space analysis during the orthodontic treatment planning.
      Depending upon the amount of space discrepancy, an accurate degree of required
      alteration in the axial relation of one or more teeth can be planned.

PMID- 28764303
TI  - Surgical Management of a Separated Endodontic Instrument using Second Generation
      Platelet Concentrate and Hydroxyapatite.
AB  - Fractured endodontic instrument is an unfortunate endodontic mishap which may
      obstruct thorough cleaning and shaping of the root canals with potential impact
      on the endodontic prognosis and treatment outcome. When the fractured segment
      lies apical to canal curvature, overzealous removal of tooth structure is
      required to gain access to the separated segment which in turn increases the
      likelihood of root fracture. In infected cases, the stage at which instrument
      separation occurs is crucial as root canal disinfection is jeopardized. This case
      report describes the surgical retrieval of a fractured endodontic file from the
      mesiobuccal canal of mandibular first molar by limited resection of mesial root.
      Second generation platelet concentrate called Platelet Rich Fibrin (PRF) and
      nanocrystalline hydroxyapatite and beta-tricalcium phosphate bone graft was
      placed to fill the surgical defect as the combination enhances the regenerative
      effect of PRF by exerting an osteoconductive effect in the bony defect area. The
      clinical and radiographic examination after eighteen months revealed complete
      periapical healing.

PMID- 28764304
TI  - Large Solitary Neurofibroma of Face in a Paediatric Patient.
AB  - Neurofibroma is a rare, benign, neurogenic tumour which may present as multiple
      lesions as a part of neurofibromatosis syndrome or as a solitary mass. This paper
      reports a case of large solitary neurofibroma of face in a young female patient.
      Clinical presentation, imaging characteristics and management of the pathology
      has been described in detail. The paper also reviews English literature for
      similar cases.

PMID- 28764305
TI  - A Wide Spread Red Lesion on the Surface of the Tongue-A Case Report and Review of
      Differential Diagnosis.
AB  - The tongue is considered to be the strongest muscular organ in the body and a
      very important structure in the oral cavity. It is involved in various critical
      functions such as taste, speech, chewing and deglutition. It has been known to be
      a harbinger of systemic health and disease. Lesions occurring on the tongue vary
      widely in colour and consistency. Widespread red lesions on the tongue need to be
      differentiated carefully from each other for a proper diagnosis and treatment and
      must be followed up for recurrence. The present case report demonstrates a
      widespread longstanding recurrent red lesion occurring on the surface of the
      tongue, its diagnosis and management.

PMID- 28764306
TI  - Radix Distolingualis: A Case Report, Review and Endodontic Treatment Guidelines.
AB  - Variation in the root and canal morphology of maxillary second molars is quite
      common. The most common configuration is three roots and three or four canals.
      But the presence of an additional palatal root is rather uncommon and has been
      reported to have an incidence of 1.4%. The extra root is located mesiolingual or
      distolingual to the primary palatal root. This is a unique case report that
      describes the successful endodontic management of a maxillary second molar with
      Radix Distolingualis (RDL). Identification of this variation was done through
      clinical examination, multi-angled radiographs, surgical operating microscope and
      an accurate assessment of this morphology was made with the help of Cone Beam
      Computed Tomography (CBCT) imaging. In addition, this article also discusses the
      literature review, guidelines for diagnosis and treatment of RDL.

PMID- 28764307
TI  - Infantile Alexander Disease: Case Report and Review of Literature.
AB  - Alexander Disease (AD) is an autosomal dominant leukodystrophy and occurs
      predominantly in infants and children. It usually results in death within ten
      years after onset. Among the four subtypes, infantile form comprises the most of
      affected individuals. It presents in the first two years of life, typically with
      progressive psychomotor deficiency, loss of developmental milestones, seizures,
      and pyramidal signs. Clinical and magnetic resonance image findings usually
      establish diagnosis of AD. Here, we present a case of Infantile AD with
      characteristic clinical and radiological features.

PMID- 28764308
TI  - Familial Cancers of Head and Neck Region.
AB  - Cancers that occur in families more often than would be expected by chance are
      termed as familial cancers. They occur due to an inherited genetic mutation and
      account for 5%-10% of all cancers. This review article presents some of the
      common Familial Cancer Syndromes (FCS) such as MEN 2B, hyperparathyroidism-jaw
      tumour syndrome, familial oral squamous cell carcinoma, melanoma, nasopharyngeal
      carcinoma, paraganglioma, neurofibroma and other syndromes associated with head
      and neck region.

PMID- 28764309
TI  - Death Rate of Dental Anaesthesia.
AB  - Death was the most important side effect of anaesthesia in dentistry. In this
      article we reviewed more than 20 studies with adequate data focusing on death
      associated with dental procedures since 1955 and found 218 deaths out of
      71,435,282 patients (3 deaths per 1,000,000 persons) with the mortality rate of
      1:327,684. In addition, mortality rate per million has dropped to half (6.2 per
      1,000,000 vs. 3 per 1,000,000) since 1955 till the last report in 2012 without
      any sex predilection. In children, most cases died in the age of two to five
      years. Hypoxia was the most common cause of death, and cardiovascular,
      respiratory, and endocrine disorders, hepatic cirrhosis, septicaemia, and
      bacterial endocarditis were the most frequent underlying systemic disease in
      deceased patients. Although rare death following general anaesthesia in
      dentistry, is a critical side effect mostly seen in patients with compromised
      health condition. Therefore, appropriate case selection in regard with patients'
      general health status as well as standard technical and equipment conditions are
      mandatory to diminish the risk of death during dental anaesthesia.

PMID- 28764310
TI  - Microleakage at the Different Implant Abutment Interface: A Systematic Review.
AB  - INTRODUCTION: Presence of gap at the implant-abutment interface, leads to
      microleakage and accumulation of bacteria which can affect the success of dental
      implants. AIM: To evaluate the sealing capability of different implant
      connections against microleakage. MATERIALS AND METHODS: In January 2017 an
      electronic search of literature was performed, in Medline, EBSCO host and Pubmed
      data base. The search was focused on ability of different implant connections in
      preventing microleakage. The related titles and abstracts available in English
      were screened, and the articles that fulfilled the inclusion criteria were
      selected for full text reading. RESULTS: In this systematic review, literature
      search initially resulted in 78 articles among which 30 articles only fulfilled
      the criteria for inclusion and were finally included in the review. Almost all
      the studies showed that there was some amount of microleakage at abutment implant
      interface. Microleakage was very less in Morse taper implants in comparison to
      other implant connections. Majority of studies showed less microleakage in static
      loading conditions and microleakage increases in dynamic loading conditions.
      CONCLUSION: In this systematic review maximum studies showed that there was some
      amount of microleakage at abutment implant interface. External hexagon implants
      failed completely to prevent microleakage in both static and dynamic loading
      conditions of implants. Internal hexagon implants mainly internal conical (Morse
      taper) implants are very promising in case of static loading and also showed less
      microleakage in dynamic loading conditions. Torque recommended by manufacturer
      should be followed strictly to get a better seal at abutment implant interface.
      Zirconia abutments are more to microleakage than Titanium abutments and there use
      should be discouraged. Zirconia abutments should be only restricted to cases
      where there was very high demand of aesthetics.

PMID- 28764311
TI  - Altmetrics - A Collated Adjunct Beyond Citations for Scholarly Impact: A
      Systematic Review.
AB  - INTRODUCTION: In emerging Figures, scholars are unifying social media tools like
      blogs, Twitter, and Mendeley into their professional communications. The online,
      open nature of these tools reveals the scholarly action to be clear and
      unambiguous. Metrics which is set on these activities could enlighten broader,
      faster measures of impact, supplementing traditional citation metrics. AIM: The
      present review aims to analyse the correlation of altmetrics with the traditional
      citations in medical research. MATERIALS AND METHODS: The search strategy used a
      combination of controlled vocabulary and free text terms. The main database
      searched were PubMed, PubMed Central, Cochrane Review, Embase and Google Scholar
      from 2010 to 2016. Out of the total 78 titles appeared seven articles fulfilled
      the criteria and were selected for the review. RESULTS: The positive correlation
      between altmetrics and traditional citations indicates that the two are not
      entirely different from each other and are familiar with each other. Altmetrics
      are usually accessible earlier and enable us to evaluate the social impact of
      scholarly research, almost at the actual time. CONCLUSION: Much work is needed to
      develop this research which will focus on the clarity of the impact signal. Thus
      newer dimensions, such as altmetrics and article-level metrics are an effort to
      explore the influence of research across the worldwide population.

PMID- 28764312
TI  - Oral Health and Quality of Life: Current Concepts.
AB  - The recognition of health related quality of life began ever since WHO expanded
      the definition of health in 1948. This has resulted in the paradigm shift of
      health and disease from a medical model to a biopsychosocial model. Oral health
      too denotes not merely the absence of disease but the general well being so that
      the person can perform functions like eating, talking and smiling and also can
      contribute creatively to the society. Health related quality of life is a trade
      off between how long and how well people live. To explain the concept various
      theoretical models have been proposed, of which the conceptual model of Wilson
      and Cleary 1995 is a comprehensive one. Even after much research and thousands of
      publications the definition of oral health related quality of life is still
      vague. But the patient's self perception about his oral health and related life
      quality are significant in clinical dental practice, dental education and
      research. It is widely shown that oral conditions can have varied impacts on
      daily living. To assess this, many measures or scales are available. They differ
      depending on the response format, number of items, context of use and the
      population in which it is applied. Patient reported outcome assessment is a less
      developed area in clinical dentistry and research and in future it has the
      potential to become the primary or secondary outcome measure in clinical
      interventional research.

PMID- 28764313
TI  - Clinician Corner- A Simple and Efficient Modified Goshgarian Arch ("T" Arch)
      Appliance for Correcting Single Tooth Scissor Bite.
AB  - Scissor bite is a rare form of malocclusion that is often accompanied by varying
      degrees of facial asymmetry. Correction and treatment of scissor bite in
      posterior teeth is a challenging job for an orthodontist. There are several
      treatment options for correction of scissor bite in posterior teeth but some have
      their own ill-effects on the dentition thus contributing further to the problem
      and some require patient compliance which compromises the outcome of the
      treatment. Therefore to overcome these drawbacks we have designed a new appliance
      to correct the molar scissor bite.

PMID- 28764314
TI  - Granular Cell Tumour of the Tongue: Report of a Case.

PMID- 28764315
TI  - A Rare Case of Bi-rooted Deciduous Canine.

PMID- 28764316
TI  - Novel Technique for Precise Juxta-Crestal Periimplant Placement and Retention of
      Platelet Rich Fibrin (PRF) Membrane.

PMID- 28764317
TI  - Retraction.
AB  - [This retracts the article DOI: 10.7860/JCDR/2015/10240.5463.].

PMID- 28764318
TI  - Correction.
AB  - [This corrects the article DOI: 10.7860/JCDR/2016/20873.8831.].

PMID- 28764319
TI  - The Intraoperative Immunohistochemical Staining of CD56 and CK19 Improves
      Surgical Decision for Thyroid Follicular Lesions.
AB  - BACKGROUND: When differential diagnosis is difficult in thyroid follicular
      lesions with overlapping histological features, the immunohistochemical staining
      can help confirm the diagnosis. We aimed to evaluate the effectiveness of rapid
      immunohistochemical stains of CD56 and cytokeratin 19 on frozen sections of
      thyroid follicular lesion and explore the possible gains and limitations of the
      practice. METHODS: Eighty-six nodules of 79 patients whose intraoperative frozen
      sections were selected as the control group, and 53 nodules of 48 patients whose
      intraoperative frozen sections were subject to rapid immunohistochemistry were
      selected as the study group. RESULTS: Five nodules (6%) in the control group were
      diagnosed as follicular neoplasm and six nodules (7%) were deferred. In the study
      group, six nodules (11%) were follicular neoplasm and none were deferred. Three
      nodules (4%) in the control group showed diagnostic discrepancy between the
      frozen and permanent diagnoses, but none in the study group. The average
      turnaround time for the frozen diagnosis of the control group was 24 minutes,
      whereas it was 54 minutes for the study group. CONCLUSIONS: Intraoperative rapid
      immunohistochemical stains significantly decreased the diagnostic discrepancy in
      this study. Considering the adverse effects of indefinite frozen diagnosis or
      discrepancy with permanent diagnoses, the intraoperative rapid
      immunohistochemical stain can help to accurately diagnose and hence provide
      guidance to surgical treatment.

PMID- 28764320
TI  - Lipoteichoic Acid Isolated from Staphylococcus aureus Induces Both Epithelial
      Mesenchymal Transition and Wound Healing in HaCaT Cells.
AB  - Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is
      recognized by Toll-like receptor 2, expressed on certain mammalian cell surfaces,
      initiating signaling cascades that include nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) and mitogen-activated protein kinase.
      There are many structural and functional varieties of LTA, which vary according
      to the different species of gram-positive bacteria that produce them. In this
      study, we examined whether LTA isolated from Staphylococcus aureus (aLTA) affects
      the expression of junction proteins in keratinocytes. In HaCaT cells, tight
      junction-related gene expression was not affected by aLTA, whereas adherens
      junction-related gene expression was modified. High doses of aLTA induced the
      phosphorylation of extracellular signal-regulated protein kinases 1 and 2, which
      in turn induced the epithelial-mesenchymal transition (EMT) of HaCaT cells. When
      cells were given a low dose of aLTA, however, NF-kappaB was activated and the
      total cell population increased. Taken together, our study suggests that LTA from
      S. aureus infections in the skin may contribute both to the outbreak of EMT
      mediated carcinogenesis and to the genesis of wound healing in a dose-dependent
      manner.

PMID- 28764321
TI  - Differentiation in Nitrogen-Converting Activity and Microbial Community Structure
      between Granular Size Fractions in a Continuous Autotrophic Nitrogen Removal
      Reactor.
AB  - The differentiations in nitrogen-converting activity and microbial community
      structure between granular size fractions in a continuous completely autotrophic
      nitrogen removal over nitrite (CANON) reactor, having a superior specific
      nitrogen removal rate of 0.24 g/(g VSS.d), were investigated by batch tests and
      high-throughput pyrosequencing analysis, respectively. Results revealed that a
      high dissolved oxygen concentration (>1.8 mg/l) could result in efficient nitrite
      accumulation with small granules (0.2-0.6 mm in diameter), because aerobic
      ammonium-oxidizing bacteria (genus Nitrosomonas) predominated therein. Meanwhile,
      intermediate size granules (1.4-2.0 mm in diameter) showed the highest nitrogen
      removal activity of 40.4 mg/(g VSS.h) under sufficient oxygen supply,
      corresponding to the relative abundance ratio of aerobic to anaerobic ammonium
      oxidizing bacteria (genus Candidatus Kuenenia) of 5.7. Additionally, a dual
      substrate competition for oxygen and nitrite would be considered as the main
      mechanism for repression of nitrite-oxidizing bacteria, and the few Nitrospira
      spp. did not remarkably affect the overall performance of the reactor. Because
      all the granular size fractions could accomplish the CANON process independently
      under oxygen limiting conditions, maintaining a diversity of granular size would
      facilitate the stability of the suspended growth CANON system.

PMID- 28764322
TI  - Phase Behavior of Magnetic Nanocolloids of Different Sizes Suspended in an Apolar
      Solvent.
AB  - We employ classical density functional theory (DFT) to investigate the phase
      behavior and composition of binary mixtures; each compound consists of hard
      spheres of different sizes with superimposed dispersion attraction. In addition
      to the dispersion attraction, molecules of one component carry an additional
      three-dimensional magnetic "spin" where the orientation-dependent spin-spin
      interaction is accounted for by the Heisenberg model. We are treating the excess
      free energy using a modified mean-field approximation (second virial coefficient)
      for the orientation-dependent pair correlation function. Depending on the
      concentration of the magnetic particles, the strength of the spin-spin coupling,
      and the size ratio of the particles, the model predicts the formation of ordered
      (polar) phases in addition to the more conventional gas and isotropic liquid
      phases. Key features of our model are a particle-size dependent shift of the gas
      liquid critical point (critical temperature and density) and a change in the
      width of the phase diagram. In the near-critical region, the latter can be
      analyzed quantitativly in terms of an effective critical exponent betaeff that
      may differ from the classical critical exponent [Formula: see text]; the
      classical value is attained in the immediate vicinity of the critical point as it
      must. The deviation between betaeff and beta can be linked to nontrivial
      composition effects along the phase boundaries.

PMID- 28764323
TI  - LipidCCS: Prediction of Collision Cross-Section Values for Lipids with High
      Precision To Support Ion Mobility-Mass Spectrometry-Based Lipidomics.
AB  - The use of collision cross-section (CCS) values derived from ion mobility-mass
      spectrometry (IM-MS) has been proven to facilitate lipid identifications. Its
      utility is restricted by the limited availability of CCS values. Recently, the
      machine-learning algorithm-based prediction (e.g., MetCCS) is reported to
      generate CCS values in a large-scale. However, the prediction precision is not
      sufficient to differentiate lipids due to their high structural similarities and
      subtle differences on CCS values. To address this challenge, we developed a new
      approach, namely, LipidCCS, to precisely predict lipid CCS values. In LipidCCS, a
      set of molecular descriptors were optimized using bioinformatic approaches to
      comprehensively describe the subtle structure differences for lipids. The use of
      optimized molecular descriptors together with a large set of standard CCS values
      for lipids (458 in total) to build the prediction model significantly improved
      the precision. The prediction precision of LipidCCS was externally validated with
      median relative errors (MRE) of ~1% using independent data sets across different
      instruments (Agilent DTIM-MS and Waters TWIM-MS) and laboratories. We also
      demonstrated that the improved precision in the predicted LipidCCS database (15
      646 lipids and 63 434 CCS values in total) could effectively reduce false
      positive identifications of lipids. Common users can freely access our LipidCCS
      web server for the following: (1) the prediction of lipid CCS values directly
      from SMILES structure; (2) database search; and (3) lipid match and
      identification. We believe LipidCCS will be a valuable tool to support IM-MS
      based lipidomics. The web server is freely available on the Internet (
      http://www.metabolomics-shanghai.org/LipidCCS/ ).

PMID- 28764325
TI  - Anion-Exchange Fibers for Improved Sample Loading in Ultra-Trace Analysis of
      Plutonium by Thermal Ionization Mass Spectrometry.
AB  - A new sample loading procedure was developed for isotope ratio measurements of
      ultratrace amounts of plutonium with thermal ionization mass spectrometry (TIMS).
      The goal was to determine the efficacy of a polymer fiber architecture for TIMS
      sample loading by following similar sample loading procedures as those used in
      bead loading. Fibers with diameter of approximately 100 MUm were prepared from
      triethylamine-quaternized-poly(vinylbenzyl chloride) cross-linked with
      diazabicyclo[2.2.2]octane. Fiber sections (2.5 mm) were loaded with 10 pg of New
      Brunswick Laboratory certified reference material (NBL CRM) 128 from an 8 M HNO3
      matrix and affixed to rhenium filaments with collodion. A single filament
      assembly was used for these analyses. Total ion counts (239Pu + 242Pu) and
      isotope ratios obtained from fiber-loaded filaments were compared to those
      measured by depositing Pu amended resin beads on the filament. Fiber loading was
      found to improve sensitivity, accuracy, and precision of isotope ratio
      measurements of plutonium when compared to the established resin bead loading
      method, while maintaining its simplicity. The average number of detected Pu+
      counts was 180% greater, and there was a 72% reduction in standard deviation of
      ratio measurements when using fiber loading. An average deviation of 0.0012
      (0.117%) from the certified isotope ratio value of NBL CRM Pu128 was measured
      when fiber loading versus a deviation of 0.0028 (0.284%) when bead loading. The
      fiber formation method presented in this study can be extended to other anion
      exchange polymer chemistries and, therefore, offers a convenient platform to
      investigate the efficacy of novel polymer chemistries in sample loading for TIMS.

PMID- 28764324
TI  - Large-Scale Structural Characterization of Drug and Drug-Like Compounds by High
      Throughput Ion Mobility-Mass Spectrometry.
AB  - Ion mobility-mass spectrometry (IM-MS) can provide orthogonal information, i.e.,
      m/z and collision cross section (CCS), for the identification of drugs and drug
      metabolites. However, only a small number of CCS values are available for drugs,
      which limits the use of CCS as an identification parameter and the assessment of
      structure-function relationships of drugs using IM-MS. Here, we report the
      development of a rapid workflow for the measurement of CCS values of a large
      number of drug or drug-like molecules in nitrogen on the widely available
      traveling wave IM-MS (TWIM-MS) platform. Using a combination of small molecule
      and polypeptide CCS calibrants, we successfully determined the nitrogen CCS
      values of 1425 drug or drug-like molecules in the MicroSource Discovery Systems'
      Spectrum Collection using flow injection analysis of 384-well plates. Software
      was developed to streamline data extraction, processing, and calibration. We
      found that the overall drug collection covers a wide CCS range for the same mass,
      suggesting a large structural diversity of these drugs. However, individual drug
      classes appear to occupy a narrow and unique space in the CCS-mass 2D spectrum,
      suggesting a tight structure-function relationship for each class of drugs with a
      specific target. We observed bimodal distributions for several antibiotic species
      due to multiple protomers, including the known fluoroquinolone protomers and the
      new finding of cephalosporin protomers. Lastly, we demonstrated the utility of
      the high-throughput method and drug CCS database by quickly and confidently
      confirming the active component in a pharmaceutical product.

PMID- 28764326
TI  - Comprehensive Study of the Flow Control Strategy in a Wirelessly Charged
      Centrifugal Microfluidic Platform with Two Rotation Axes.
AB  - Centrifugal microfluidics has been widely applied in the sample-in-answer-out
      systems for the analyses of nucleic acids, proteins, and small molecules.
      However, the inherent characteristic of unidirectional fluid propulsion limits
      the flexibility of these fluidic chips. Providing an extra degree of freedom to
      allow the unconstrained and reversible pumping of liquid is an effective strategy
      to address this limitation. In this study, a wirelessly charged centrifugal
      microfluidic platform with two rotation axes has been constructed and the flow
      control strategy in such platform with two degrees of freedom was comprehensively
      studied for the first time. Inductively coupled coils are installed on the
      platform to achieve wireless power transfer to the spinning stage. A micro servo
      motor is mounted on both sides of the stage to alter the orientation of the
      device around a secondary rotation axis on demand during stage rotation. The
      basic liquid operations on this platform, including directional transport of
      liquid, valving, metering, and mixing, are comprehensively studied and realized.
      Finally, a chip for the simultaneous determination of hexavalent chromium
      [Cr(VI)] and methanal in water samples is designed and tested based on the
      strategy presented in this paper, demonstrating the potential use of this
      platform for on-site environmental monitoring, food safety testing, and other
      life science applications.

PMID- 28764327
TI  - Enhanced Photoluminescence Emission and Thermal Stability from Introduced Cation
      Disorder in Phosphors.
AB  - Optimizing properties of phosphors for use in white-light-emitting diodes (WLEDs)
      is an important materials challenge. Most phosphors have a low level of lattice
      disorder due to mismatch between the host and activator cations. Here we show
      that deliberate introduction of high levels of cation disorder leads to
      significant improvements in quantum efficiency, stability to thermal quenching,
      and emission lifetime in Sr1.98-x(Ca0.55Ba0.45)xSi5N8:Eu0.02 (x = 0-1.5)
      phosphors. Replacing Sr by a (Ca0.55Ba0.45) mixture with the same average radius
      increases cation size variance, resulting in photoluminescence emission increases
      of 20-26% for the x = 1.5 sample relative to the x = 0 parent across the 25-200 
      degrees C range that spans WLED working temperatures. Cation disorder suppresses
      nonradiative processes through disruption of lattice vibrations and creates deep
      traps that release electrons to compensate for thermal quenching. Introduction of
      high levels of cation disorder may thus be a very useful general approach for
      improving the efficiency of luminescent materials.

PMID- 28764328
TI  - Protospacer Adjacent Motif-Induced Allostery Activates CRISPR-Cas9.
AB  - CRISPR-Cas9 is a genome editing technology with major impact in life sciences. In
      this system, the endonuclease Cas9 generates double strand breaks in DNA upon RNA
      guided recognition of a complementary DNA sequence, which strictly requires the
      presence of a protospacer adjacent motif (PAM) next to the target site. Although
      PAM recognition is essential for cleavage, it is unknown whether and how PAM
      binding activates Cas9 for DNA cleavage at spatially distant sites. Here, we find
      evidence of a PAM-induced allosteric mechanism revealed by microsecond molecular
      dynamics simulations. PAM acts as an allosteric effector and triggers the
      interdependent conformational dynamics of the Cas9 catalytic domains (HNH and
      RuvC), responsible for concerted cleavage of the two DNA strands. Targeting such
      an allosteric mechanism should enable control of CRISPR-Cas9 functionality.

PMID- 28764329
TI  - Molecular Simulation of Ionic Polyimides and Composites with Ionic Liquids as Gas
      Separation Membranes.
AB  - Polyimides are at the forefront of advanced membrane materials for CO2 capture
      and gas-purification processes. Recently, ionic polyimides (i-PIs) have been
      reported as a new class of condensation polymers that combine structural
      components of both ionic liquids (ILs) and polyimides through covalent linkages.
      In this study, we report CO2 and CH4 adsorption and structural analyses of an i
      PI and an i-PI + IL composite containing [C4mim][Tf2N]. The combination of
      molecular dynamics (MD) and grand canonical Monte Carlo (GCMC) simulations is
      used to compute the gas solubility and the adsorption performance with respect to
      the density, fractional free volume (FFV), and surface area of the materials. Our
      results highlight the polymer relaxation process and its correlation to the gas
      solubility. In particular, the surface area can provide meaningful guidance with
      respect to the gas solubility, and it tends to be a more sensitive indicator of
      the adsorption behavior versus only considering the system density and FFV. For
      instance, as the polymer continues to relax, the density, FFV, and pore-size
      distribution remain constant while the surface area can continue to increase,
      enabling more adsorption. Structural analyses are also conducted to identify the
      nature of the gas adsorption once the ionic liquid is added to the polymer. The
      presence of the IL significantly displaces the CO2 molecules from the ligand
      nitrogen sites in the neat i-PI to the imidazolium rings in the i-PI + IL
      composite. However, the CH4 molecules move from the imidazolium ring sites in the
      neat i-PI to the ligand nitrogen atoms in the i-PI + IL composite. These
      molecular details can provide critical information for the experimental design of
      highly selective i-PI materials as well as provide additional guidance for the
      interpretation of the simulated adsorption systems.

PMID- 28764330
TI  - Multicomponent Synthesis of Diverse o-Arylated Benzamides via o-Aminophenol (OAP)
      Directed C(sp2)-H Arylation.
AB  - o-Aminophenol (OAP) has been discovered as practical precursor of directing group
      (DG) in the palladium-catalyzed aromatic C-H arylation of benzamides. This newly
      identified, simple, and low cost DG has exhibited broad substrate tolerance in
      the rapid synthesis of various o-arylated benzamides via direct assemblies of
      benzoyl chlorides, aryl iodides, and different o-aminophenols in the form of step
      economical multicomponent reaction.

PMID- 28764331
TI  - Poly(ethylene glycol) (PEG) in a Polyethylene (PE) Framework: A Simple Model for
      Simulation Studies of a Soluble Polymer in an Open Framework.
AB  - Canonical molecular dynamics simulations are performed to investigate the
      behavior of single-chain and multiple-chain poly(ethylene glycol) (PEG) contained
      within a cubic framework spanned by polyethylene (PE) chains. This simple model
      is the first of its kind to study the chemical physics of polymer-threaded
      organic frameworks, which are materials with potential applications in catalysis
      and separation processes. For a single-chain 9-mer, 14-mer, and 18-mer in a small
      framework, the PEG will interact strongly with the framework and assume a more
      linear geometry chain with an increased radius of gyration Rg compared to that of
      a large framework. The interaction between PEG and the framework decreases with
      increasing mesh size in both vacuum and water. In the limit of a framework with
      an infinitely large cavity (infinitely long linkers), PEG behavior approaches
      simulation results without a framework. The solvation of PEG is simulated by
      adding explicit TIP3P water molecules to a 6-chain PEG 14-mer aggregate confined
      in a framework. The 14-mer chains are readily solvated and leach out of a large
      2.6 nm mesh framework. There are fewer water-PEG interactions in a small 1.0 nm
      mesh framework, as indicated by a smaller number of hydrogen bonds. The PEG
      aggregate, however, still partially dissolves but is retained within the 1.0 nm
      framework. The preliminary results illustrate the effectiveness of the simple
      model in studying polymer-threaded framework materials and in optimizing polymer
      or framework parameters for high performance.

PMID- 28764332
TI  - Pharmaceutical Removal from Water Effluents by Adsorption on Activated Carbons: A
      Monte Carlo Simulation Study.
AB  - Adsorption on activated carbons of five pharmaceutical molecules (ibuprofen,
      diclofenac, naproxen, paracetamol, and amoxicillin) in aqueous mixtures has been
      investigated by molecular simulations using the Grand Canonical Monte Carlo
      (GCMC) method. A virtual nanoporous carbon model based on polyaromatic units with
      defects and polar-oxygenated sites was used for this purpose. The simulation
      results show excellent agreement with available experimental data. The adsorption
      capacities of the carbons for the five drugs were quite different and were
      linked, essentially, to their molecular dimensions and atom affinities. The
      uptake behavior follows the trend PRM > DCF, NPX > IBP > AMX in all the studied
      structures. This work is a further step in order to describe macroscopic
      adsorption performance of activated carbons in drug removal applications.

PMID- 28764333
TI  - Trimethylation Enhancement Using 13C-Diazomethane: Gas-Phase Charge Inversion of
      Modified Phospholipid Cations for Enhanced Structural Characterization.
AB  - Methylation of phospholipids (PL) leads to increased uniformity in positive
      electrospray ionization (ESI) efficiencies across the various PL subclasses. This
      effect is realized in the approach referred to as "trimethylation enhancement
      using 13C-diazomethane" (13C-TrEnDi), which results in the methyl esterification
      of all acidic sites and the conversion of amines to quaternary ammonium sites.
      Collision-induced dissociation (CID) of these cationic modified lipids enables
      class identification by forming distinctive headgroup fragments based on the
      number of 13C atoms incorporated during derivatization. However, there are no
      distinctive fragment ions in positive mode that provide fatty acyl information
      for any of the modified lipids. Gas-phase ion/ion reactions of 13C-TrEnDi
      modified phosphatidylethanolamine (PE), phosphatidylserine (PS),
      phosphatidylcholine (PC), and sphingomyelin (SM) cations with dicarboxylate
      anions are shown to charge-invert the positively charged phospholipids to the
      negative mode. An electrostatically bound complex anion is shown to fragment
      predominantly via a novel headgroup dication transfer to the reagent anion.
      Fragmentation of the resulting anionic product yields fatty acyl information, in
      the case of the glycerophospholipids (PE, PS, and PC), via ester bond cleavage.
      Analogous information is obtained from modified SM lipid anions via amide bond
      cleavage. Fragmentation of the anions generated from charge inversion of the 13C
      TrEnDi-modified phospholipids was also found to yield lipid class information
      without having to perform CID in positive mode. The combination of 13C-TrEnDi
      modification of lipid mixtures with charge inversion to the negative-ion mode
      retains the advantages of uniform ionization efficiency in the positive-ion mode
      with the additional structural information available in the negative-ion mode
      without requiring the lipids to be ionized directly in both ionization modes.

PMID- 28764334
TI  - Dimers of formic acid: Structures, stability, and double proton transfer.
AB  - A stochastic search of the potential energy surface for the formic acid dimers
      results in 21 well-defined minima. A number of structures are reported here for
      the first time, others have already been experimentally detected or
      computationally predicted. Four types of different hydrogen bonds (HBs) are at
      play stabilizing the clusters: primary C=O? H-O and H-O? H-O and secondary C=O? H
      C and H-O? H-C HBs corresponding to well-characterized bonding paths are
      identified. A novel C=O? C stabilizing interaction is also reported. The double
      proton transfer reaction is calculated to occur in a synchronous fashion, with an
      energy barrier smaller than the energy needed to break up the dimers.

PMID- 28764335
TI  - Effects of a "bound" substrate layer on the dynamics of supported polymer films.
AB  - It is widely appreciated that an attractive polymer-substrate interaction can
      slow relaxation in thin supported polymer films and polymer nanocomposites.
      Recent measurements and simulations on nancomposites have indicated that this
      slowing of polymer dynamics occurs more strongly near a highly attractive
      particle surface where a "bound" layer having a much lower mobility can form,
      strongly influencing the thermodynamics and dynamics of the film. Here we use
      molecular simulations to show that a bound interfacial layer having a very
      similar nature arises in thin supported polymer films when the polymer-polymer
      attraction is stronger than the polymer-polymer interaction strength. This bound
      polymer layer effectively insulates the remainder of the film from the strong
      interfacial interactions, and the resulting thermodynamically determined Tg is
      relatively insensitive to the polymer-substrate interaction strength when it
      exceeds that of the polymer-polymer interactions. The presence of this layer
      gives rise to an additional relaxation process in the self-intermediate
      scattering function that is not observed in the bulk material and leads to a
      slowing down of the average relaxation time of the film as a whole. On the other
      hand, the average relaxation time of the film outside the bound layer does not
      grow in proportion to the strength of the substrate attraction due to the weak
      coupling of the substrate relaxation to the relaxation in the interior of the
      film. At large substrate attraction, the bound layer effectively "cloaks" the
      substrate, reducing the effect of the polymer-surface interaction on Tg.

PMID- 28764336
TI  - Erratum: "Ultrafast vibrational spectroscopy (2D-IR) of CO2 in ionic liquids:
      Carbon capture from carbon dioxide's point of view" [J. Chem. Phys. 142, 212425
      (2015)].

PMID- 28764337
TI  - Dynamical pruning of the multiconfiguration time-dependent Hartree (DP-MCTDH)
      method: An efficient approach for multidimensional quantum dynamics.
AB  - We present two strategies for combining dynamical pruning with the
      multiconfiguration time-dependent Hartree (DP-MCTDH) method, where dynamical
      pruning means on-the-fly selection of relevant basis functions. The first
      strategy prunes the primitive basis that represents the single-particle functions
      (SPFs). This is useful for smaller systems that require many primitive basis
      functions per degree of freedom, as we will illustrate for NO2. Furthermore, this
      allows for higher-dimensional mode combination and partially lifts the sum-of
      product-form requirement onto the structure of the Hamiltonian, as we illustrate
      for nonadiabatic 24-dimensional pyrazine. The second strategy prunes the set of
      configurations of SPF at each time step. We show that this strategy yields
      significant speed-ups with factors between 5 and 50 in computing time, making it
      competitive with the multilayer MCTDH method.

PMID- 28764338
TI  - Explicit correlation treatment of the six-dimensional potential energy surface
      and predicted infrared spectra for OCS-H2.
AB  - An effective six-dimensional ab initio potential energy surface (PES) for H2-OCS
      which explicitly includes the intramolecular stretch normal modes of carbonyl
      sulfide (OCS) is presented. The electronic structure computations are carried out
      using the explicitly correlated coupled cluster [CCSD(T)-F12] method with the
      augmented correlation-consistent aug-cc-pVTZ basis set, and the accuracy is
      critically tested by performing a series of benchmark calculations. Analytic four
      dimensional PESs are obtained by least-squares fitting vibrationally averaged
      interaction energies to the Morse/long-range potential model. These fits to 13
      485 points have a root-mean-square deviation (RMSD) of 0.16 cm-1. The combined
      radial discrete variable representation/angular finite basis representation
      method and the Lanczos algorithm were employed to evaluate the rovibrational
      energy levels for five isotopic species of the OCS-hydrogen complexes. The
      predicted transition frequencies and intensities based on the resulting
      vibrationally averaged PESs are in good agreement with the available experimental
      values, whose RMSDs are smaller than 0.004 cm-1 for five different species of OCS
      hydrogen complexes. The calculated infrared band origin shifts for all five
      species of OCS-hydrogen complexes are only 0.03 cm-1 smaller than the
      corresponding experimental values. These validate the high quality of our PESs
      which can be used for modeling OCS doped in hydrogen clusters to further study
      quantum solution and microscopic superfluidity. In addition, the analytic
      coordinate transformation functions between isotopologues are also derived due to
      the center of mass shifting of different isotope substitutes.

PMID- 28764339
TI  - An adaptive solution to the chemical master equation using tensors.
AB  - Solving the chemical master equation directly is difficult due to the curse of
      dimensionality. We tackle that challenge by a numerical scheme based on the
      quantized tensor train (QTT) format, which enables us to represent the solution
      in a compressed form that scales linearly with the dimension. We recast the
      finite state projection in this QTT framework and allow it to expand adaptively
      based on proven error criteria. The end result is a QTT-formatted matrix
      exponential that we evaluate through a combination of the inexact uniformization
      technique and the alternating minimal energy algorithm. Our method can detect
      when the equilibrium distribution is reached with an inexpensive test that
      exploits the structure of the tensor format. We successfully perform numerical
      tests on high-dimensional problems that had been out of reach for classical
      approaches.

PMID- 28764340
TI  - A matrix isolation ESR and theoretical study of MgN.
AB  - Matrix isolation experiments have been conducted on the Mg14N, 25Mg14N, Mg15N,
      and 25Mg15N radicals which were formed by the reaction of a plume of magnesium
      metal produced with laser ablation and either acetonitrile vapour or nitrogen
      atoms. The radicals were isolated in an inert neon matrix at 4.3 K and studied
      with electron spin resonance spectroscopy. The ground electronic state of MgN was
      determined to be 4Sigma-. The following magnetic parameters were determined
      experimentally for MgN: g? = 2.004 78 (2), g? = 2.001 72 (4), |D| = 9797 (6) MHz,
      A?(14N) = 19.7 (2) MHz, A? (14N) = -4.0 (3) MHz, A?(15N) = 27.5 (3) MHz, A? (15N)
      = -5.7 (3) MHz, A? (25Mg) = -60.7 (5) MHz, and A?(25Mg) = -65 (3) MHz. The low
      lying electronic states of MgN were also investigated using the complete active
      space multiconfigurational self-consistent field technique. By plotting the
      potential energy surface, theoretical parameters for the ground state with a
      configuration of 5sigma26sigma27sigma12pi12pi1 were able to be determined,
      including re = 2.090 A and De = 11.28 kcal/mol.

PMID- 28764341
TI  - Including surface ligand effects in continuum elastic models of nanocrystal
      vibrations.
AB  - The measured low frequency vibrational energies of some quantum dots (QDs)
      deviate from the predictions of traditional elastic continuum models. Recent
      experiments have revealed that these deviations can be tuned by changing the
      ligands that passivate the QD surface. This observation has led to speculation
      that these deviations are due to a mass-loading effect of the surface ligands. In
      this article, we address this speculation by formulating a continuum elastic
      theory that includes the dynamical loading by elastic surface ligands. We
      demonstrate that this model is capable of accurately reproducing the l = 0 phonon
      energy across a variety of different QD samples, including cores with different
      ligand identities and epitaxially grown CdSe/CdS core/shell heterostructures. We
      highlight that our model performs well even in the small QD regime, where
      traditional elastic continuum models are especially prone to failure.
      Furthermore, we show that our model combined with Raman measurements can be used
      to infer the elastic properties of surface bound ligands, such as sound
      velocities and elastic moduli, that are otherwise challenging to measure.

PMID- 28764342
TI  - Drying and wetting transitions of a Lennard-Jones fluid: Simulations and density
      functional theory.
AB  - We report a theoretical and simulation study of the drying and wetting phase
      transitions of a truncated Lennard-Jones fluid at a flat structureless wall.
      Binding potential calculations predict that the nature of these transitions
      depends on whether the wall-fluid attraction has a long ranged (LR) power law
      decay or is instead truncated, rendering it short ranged (SR). Using grand
      canonical Monte Carlo simulation and classical density functional theory, we
      examine both cases in detail. We find that for the LR case wetting is first
      order, while drying is continuous (critical) and occurs exactly at zero
      attractive wall strength, i.e., in the limit of a hard wall. In the SR case,
      drying is also critical but the order of the wetting transition depends on the
      truncation range of the wall-fluid potential. We characterize the approach to
      critical drying and wetting in terms of the density and local compressibility
      profiles and via the finite-size scaling properties of the probability
      distribution of the overall density. For the LR case, where the drying point is
      known exactly, this analysis allows us to estimate the exponent nu?, which
      controls the parallel correlation length, i.e., the extent of vapor bubbles at
      the wall. Surprisingly, the value we obtain is over twice that predicted by mean
      field and renormalization group calculations, despite the fact that our three
      dimensional system is at the upper critical dimension where mean field theory for
      critical exponents is expected to hold. Possible reasons for this discrepancy are
      discussed in the light of fresh insights into the nature of near critical finite
      size effects.

PMID- 28764343
TI  - Generalized model for the diffusion of solvents in glassy polymers: From Fickian
      to Super Case II.
AB  - The diffusion of small solvent molecules in glassy polymers may take on a variety
      of different forms. Fickian, anomalous, Case II and Super Case II diffusion have
      all been observed, and theoretical models exist that describe each specific type
      of behavior. Here we present a single generalized kinetic model capable of
      yielding all these different types of diffusion on the basis of just two
      parameters. The principal determinant of the type of diffusion is observed to be
      a dimensionless parameter, gamma, that describes the influence of solvent-induced
      swelling in lowering the potential barriers separating available solvent sites. A
      second parameter, eta, which characterizes the effect of the solvent in reducing
      the potential energy of a solvent molecule when at rest at an available site,
      only influences the type of diffusion to a lesser extent. The theoretical
      analysis does not include any effects that are explicitly non-local in time, an
      example of which is the inclusion of polymer viscosity in the Thomas-Windle
      model; it thus represents a variant of Fick's second law utilizing a
      concentration-dependent diffusivity when eta is small. To check the significance
      of time-delayed swelling, a simulation of a modified model was performed that
      contained a history-dependent term. The results were found to be very similar to
      those in the time-local model.

PMID- 28764344
TI  - Time domain simulation of Gd3+-Gd3+ distance measurements by EPR.
AB  - Gd3+-based spin labels are useful as an alternative to nitroxides for
      intramolecular distance measurements at high fields in biological systems.
      However, double electron-electron resonance (DEER) measurements using model Gd3+
      complexes featured a low modulation depth and an unexpected broadening of the
      distance distribution for short Gd3+-Gd3+ distances, when analysed using the
      software designed for S = 1/2 pairs. It appears that these effects result from
      the different spectroscopic characteristics of Gd3+-the high spin, the zero field
      splitting (ZFS), and the flip-flop terms in the dipolar Hamiltonian that are
      often ignored for spin-1/2 systems. An understanding of the factors affecting the
      modulation frequency and amplitude is essential for the correct analysis of Gd3+
      Gd3+ DEER data and for the educated choice of experimental settings, such as Gd3+
      spin label type and the pulse parameters. This work uses time-domain simulations
      of Gd3+-Gd3+ DEER by explicit density matrix propagation to elucidate the factors
      shaping Gd3+ DEER traces. The simulations show that mixing between the |+1/2, 
      1/2> and |-1/2, +1/2> states of the two spins, caused by the flip-flop term in
      the dipolar Hamiltonian, leads to dampening of the dipolar modulation. This
      effect may be mitigated by a large ZFS or by pulse frequency settings allowing
      for a decreased contribution of the central transition and the one adjacent to
      it. The simulations reproduce both the experimental line shapes of the Fourier
      transforms of the DEER time domain traces and the trends in the behaviour of the
      modulation depth, thus enabling a more systematic design and analysis of Gd3+
      DEER experiments.

PMID- 28764345
TI  - Analytic energy gradients for the coupled-cluster singles and doubles with
      perturbative triples method with the density-fitting approximation.
AB  - An efficient implementation of analytic gradients for the coupled-cluster singles
      and doubles with perturbative triples [CCSD(T)] method with the density-fitting
      (DF) approximation, denoted as DF-CCSD(T), is reported. For the molecules
      considered, the DF approach substantially accelerates conventional CCSD(T)
      analytic gradients due to the reduced input/output time and the acceleration of
      the so-called "gradient terms": formation of particle density matrices (PDMs),
      computation of the generalized Fock-matrix (GFM), solution of the Z-vector
      equation, formation of the effective PDMs and GFM, back-transformation of the
      PDMs and GFM, from the molecular orbital to the atomic orbital (AO) basis, and
      computation of gradients in the AO basis. For the largest member of the molecular
      test set considered (C6H14), the computational times for analytic gradients (with
      the correlation-consistent polarized valence triple-zeta basis set in serial) are
      106.2 [CCSD(T)] and 49.8 [DF-CCSD(T)] h, a speedup of more than 2-fold. In the
      evaluation of gradient terms, the DF approach completely avoids the use of four
      index two-electron integrals. Similar to our previous studies on DF-second-order
      Moller-Plesset perturbation theory and DF-CCSD gradients, our formalism employs 2
      and 3-index two-particle density matrices (TPDMs) instead of 4-index TPDMs.
      Errors introduced by the DF approximation are negligible for equilibrium
      geometries and harmonic vibrational frequencies.

PMID- 28764346
TI  - Resonant inelastic x-ray scattering and photoemission measurement of O2: Direct
      evidence for dependence of Rydberg-valence mixing on vibrational states in O 1s 
      > Rydberg states.
AB  - High-resolution resonant inelastic x-ray scattering (RIXS) and low-energy
      photoemission spectra of oxygen molecules have been measured for investigating
      the electronic structure of Rydberg states in the O 1s -> sigma* energy region.
      The electronic characteristics of each Rydberg state have been successfully
      observed, and new assignments are made for several states. The RIXS spectra
      clearly show that vibrational excitation is very sensitive to the electronic
      characteristics because of Rydberg-valence mixing and vibronic coupling in O2.
      This observation constitutes direct experimental evidence that the Rydberg
      valence mixing characteristic depends on the vibrational excitation near the
      avoided crossing of potential surfaces. We also measured the photoemission
      spectra of metastable oxygen atoms (O*) from O2 excited to 1s -> Rydberg states.
      The broadening of the 4p Rydberg states of O* has been found with isotropic
      behavior, implying that excited oxygen molecules undergo dissociation with a
      lifetime of the order of 10 fs in 1s -> Rydberg states.

PMID- 28764347
TI  - One-particle many-body Green's function theory: Algebraic recursive definitions,
      linked-diagram theorem, irreducible-diagram theorem, and general-order
      algorithms.
AB  - A thorough analytical and numerical characterization of the whole perturbation
      series of one-particle many-body Green's function (MBGF) theory is presented in a
      pedagogical manner. Three distinct but equivalent algebraic (first-quantized)
      recursive definitions of the perturbation series of the Green's function are
      derived, which can be combined with the well-known recursion for the self-energy.
      Six general-order algorithms of MBGF are developed, each implementing one of the
      three recursions, the DeltaMPn method (where n is the perturbation order) [S.
      Hirata et al., J. Chem. Theory Comput. 11, 1595 (2015)], the automatic generation
      and interpretation of diagrams, or the numerical differentiation of the exact
      Green's function with a perturbation-scaled Hamiltonian. They all display the
      identical, nondivergent perturbation series except DeltaMPn, which agrees with
      MBGF in the diagonal and frequency-independent approximations at 1<=n<=3 but
      converges at the full-configuration-interaction (FCI) limit at n=infinity (unless
      it diverges). Numerical data of the perturbation series are presented for
      Koopmans and non-Koopmans states to quantify the rate of convergence towards the
      FCI limit and the impact of the diagonal, frequency-independent, or DeltaMPn
      approximation. The diagrammatic linkedness and thus size-consistency of the one
      particle Green's function and self-energy are demonstrated at any perturbation
      order on the basis of the algebraic recursions in an entirely time-independent
      (frequency-domain) framework. The trimming of external lines in a one-particle
      Green's function to expose a self-energy diagram and the removal of reducible
      diagrams are also justified mathematically using the factorization theorem of
      Frantz and Mills. Equivalence of DeltaMPn and MBGF in the diagonal and frequency
      independent approximations at 1<=n<=3 is algebraically proven, also ascribing the
      differences at n = 4 to the so-called semi-reducible and linked-disconnected
      diagrams.

PMID- 28764348
TI  - Fluctuation correction for the critical transition of symmetric homopolymer
      blends.
AB  - Monte Carlo simulations are performed on structurally symmetric binary
      homopolymer blends over a wide range of invariant polymerization indices, N-. A
      finite-size scaling analysis reveals that certain critical exponents deviate from
      the expected 3D-Ising values as N- increases. However, the deviations are
      consistent with previous simulations and can be attributed to the fact that the
      system crosses over to mean-field behavior when the molecules become too large
      relative to the size of the simulation box. Nevertheless, the finite-size scaling
      techniques provide precise predictions for the position of the critical
      transition. Using a previous calibration of the Flory-Huggins interaction
      parameter, chi, we confirm that the critical point scales as (chiN)c=2+cN--1/2
      for large N-, and more importantly we are able to extract a reliable estimate,
      c~1.5, for the universal constant.

PMID- 28764349
TI  - Efficient local-orbitals based method for ultrafast dynamics.
AB  - Computer simulations are invaluable for the study of ultrafast phenomena, as they
      allow us to directly access the electron dynamics. We present an efficient method
      for simulating the evolution of electrons in molecules under the influence of
      time-dependent electric fields, based on the Gaussian tight binding model. This
      model improves upon standard self-charge-consistent tight binding by the
      inclusion of polarizable orbitals and a self-consistent description of charge
      multipoles. Using the examples of bithiophene, terthiophene, and tetrathiophene,
      we show that this model produces electrostatic, electrodynamic, and explicitly
      time-dependent properties in strong agreement with density-functional theory, but
      at a small fraction of the cost.

PMID- 28764350
TI  - Dynamic mapping of conical intersection seams: A general method for incorporating
      the geometric phase in adiabatic dynamics in polyatomic systems.
AB  - The incorporation of the geometric phase in single-state adiabatic dynamics near
      a conical intersection (CI) seam has so far been restricted to molecular systems
      with high symmetry or simple model Hamiltonians. This is due to the fact that the
      ab initio determined derivative coupling (DC) in a multi-dimensional space is not
      curl-free, thus making its line integral path dependent. In a recent work [C. L.
      Malbon et al., J. Chem. Phys. 145, 234111 (2016)], we proposed a new and general
      approach based on an ab initio determined diabatic representation consisting of
      only two electronic states, in which the DC is completely removable, so that its
      line integral is path independent in the simply connected domains that exclude
      the CI seam. Then with the CIs included, the line integral of the single-valued
      DC can be used to construct the complex geometry-dependent phase needed to
      exactly eliminate the double-valued character of the real-valued adiabatic
      electronic wavefunction. This geometry-dependent phase gives rise to a vector
      potential which, when included in the adiabatic representation, rigorously
      accounts for the geometric phase in a system with an arbitrary locus of the CI
      seam and an arbitrary number of internal coordinates. In this work, we
      demonstrate this approach in a three-dimensional treatment of the tunneling
      facilitated dissociation of the S1 state of phenol, which is affected by a Cs
      symmetry allowed but otherwise accidental seam of CI. Here, since the space is
      three-dimensional rather than two-dimensional, the seam is a curve rather than a
      point. The nodal structure of the ground state vibronic wavefunction is shown to
      map out the seam of CI.

PMID- 28764351
TI  - Using strain to control molecule chemisorption on silicene.
AB  - The strain dependence of benzene chemisorption on a silicene freestanding layer
      has been studied by means of density functional theory calculations. It appears
      that the molecule, which is adsorbed via a [4+2] pseudo-cycloaddition on the
      substrate, is more stable when adsorbed on strained than on unstrained silicene
      since the adsorption energy increases (in absolute value) with tensile or
      compressive strain. These results, which were not easily predictable, are
      interpreted in terms of strain-induced reinforcement of the Si-C bonds, formation
      of a pz-like atomic orbital at the silicene atoms, which augments the silicene
      reactivity and, for compressive or large tensile strains, increasing of the sp3
      character of the Si-Si bonds.

PMID- 28764352
TI  - Nanolayering around and thermal resistivity of the water-hexagonal boron nitride
      interface.
AB  - The water-hexagonal boron nitride interface was investigated by molecular
      dynamics simulations. Since the properties of the interface change significantly
      with the interatomic potential, a new method for calibrating the solid-liquid
      interatomic potential is proposed based on the experimental energy of the
      interface. The result is markedly different from that given by Lorentz-Berthelot
      mixing for the Lennard-Jones parameters commonly used in the literature.
      Specifically, the extent of nanolayering and interfacial thermal resistivity is
      measured for several interatomic potentials, and the one calibrated by the
      proposed method gives the least thermal resistivity.

PMID- 28764353
TI  - A fully tetrahedral and highly corner-sharing network model of ZnCl2 glass and
      its comparison to SiO2 glass.
AB  - Zinc chloride, ZnCl2, is intermediate between a strong and a fragile glass
      former. During computational simulations, it is therefore important to account
      for ion polarizability. This, together with the lack of suitable interatomic
      potential parameters, is the likely cause for the lack of modeling studies on
      ZnCl2 glass which contain a high degree of ZnCl4 tetrahedral units. Through using
      accurate interatomic potential parameters and applying the adiabatic core-shell
      model, the first fully tetrahedral model of ZnCl2 glass was obtained. The Cl-Zn
      Cl bond angle of 109 degrees  reproduced the ideal tetrahedral bond angle, and
      the calculated total neutron and x-ray structure factors closely replicated
      experimental findings. While 86% of the ZnCl4 tetrahedral units were corner
      sharing, 14% were found to be edge-sharing. This led to two distinct
      contributions in both the Zn-Cl-Zn bond angle distribution and in the Zn?Zn
      nearest neighbour peaks being seen. These are not apparent in studies based on
      neutron diffraction. By comparing the intermediate glass former ZnCl2 to the
      strong glass former SiO2, marked differences in ring statistics became apparent.
      The Zn-Cl-Zn bond angle of around 110 degrees  enabled 3-membered rings to form
      in significant proportions. In contrast, 3-membered rings were only present in
      SiO2 glass as defects. By calculating the ZnCl2 and SiO2 partial structure
      factors, strong similarities became visible after scaling according to nearest
      neighbour distances. Although it was apparent that the main contributions to the
      first sharp diffraction peak (FSDP) came from cation-anion correlations, the
      relative scaling of the FSDP positions in ZnCl2 and SiO2 glass was not
      understood.

PMID- 28764354
TI  - Efficient steady-state solver for hierarchical quantum master equations.
AB  - Steady states play pivotal roles in many equilibrium and non-equilibrium open
      system studies. Their accurate evaluations call for exact theories with rigorous
      treatment of system-bath interactions. Therein, the hierarchical equations-of
      motion (HEOM) formalism is a nonperturbative and non-Markovian quantum
      dissipation theory, which can faithfully describe the dissipative dynamics and
      nonlinear response of open systems. Nevertheless, solving the steady states of
      open quantum systems via HEOM is often a challenging task, due to the vast number
      of dynamical quantities involved. In this work, we propose a self-consistent
      iteration approach that quickly solves the HEOM steady states. We demonstrate its
      high efficiency with accurate and fast evaluations of low-temperature thermal
      equilibrium of a model Fenna-Matthews-Olson pigment-protein complex. Numerically
      exact evaluation of thermal equilibrium Renyi entropies and stationary emission
      line shapes is presented with detailed discussion.

PMID- 28764355
TI  - Understanding the catalytic activity of nanoporous gold: Role of twinning in fcc
      lattice.
AB  - Nanoporous gold (NPG) prepared by de-alloying Al2Au exhibits correlation between
      the high catalytic reactivity towards CO oxidation and the density of twinning
      defects in the fcc lattice of NPG. It was also discovered that on the internal
      surface of NPG, quite common twinning defects can create close-packed rows of six
      coordinated catalytically active Au atoms denoted as W-chains. In this work,
      using density functional theory methods, we investigate energy conditions for
      formation, thermal stability, and chemical reactivity of these active sites. The
      possibility of dioxygen chemisorption on various surface sites is studied in
      detail. A contribution from the dispersion interactions is also considered. The
      calculated surface density of the active six-coordinated atoms in NPG comparable
      with that of supported gold nanoparticle catalysts, exothermic chemisorption of
      dioxygen, and the energy profiles of reaction pathways for CO oxidation indicate
      that the six-coordinated sites created by twinning can significantly contribute
      to the catalytic activity of NPG.

PMID- 28764356
TI  - Arm retraction dynamics of entangled star polymers: A forward flux sampling
      method study.
AB  - The study of dynamics and rheology of well-entangled branched polymers remains a
      challenge for computer simulations due to the exponentially growing terminal
      relaxation times of these polymers with increasing molecular weights. We present
      an efficient simulation algorithm for studying the arm retraction dynamics of
      entangled star polymers by combining the coarse-grained slip-spring (SS) model
      with the forward flux sampling (FFS) method. This algorithm is first applied to
      simulate symmetric star polymers in the absence of constraint release (CR). The
      reaction coordinate for the FFS method is determined by finding good agreement of
      the simulation results on the terminal relaxation times of mildly entangled stars
      with those obtained from direct shooting SS model simulations with the relative
      difference between them less than 5%. The FFS simulations are then carried out
      for strongly entangled stars with arm lengths up to 16 entanglements that are far
      beyond the accessibility of brute force simulations in the non-CR condition.
      Apart from the terminal relaxation times, the same method can also be applied to
      generate the relaxation spectra of all entanglements along the arms which are
      desired for the development of quantitative theories of entangled branched
      polymers. Furthermore, we propose a numerical route to construct the
      experimentally measurable relaxation correlation functions by effectively linking
      the data stored at each interface during the FFS runs. The obtained star arm end
      to-end vector relaxation functions Phi(t) and the stress relaxation function G(t)
      are found to be in reasonably good agreement with standard SS simulation results
      in the terminal regime. Finally, we demonstrate that this simulation method can
      be conveniently extended to study the arm-retraction problem in entangled star
      polymer melts with CR by modifying the definition of the reaction coordinate,
      while the computational efficiency will depend on the particular slip-spring or
      slip-link model employed.

PMID- 28764357
TI  - Solution properties of star polyelectrolytes having a moderate number of arms.
AB  - We investigate polyelectrolyte stars having a moderate number of arms by
      molecular dynamics simulations of a coarse-grained model over a range of
      polyelectrolyte concentrations, where both the counter-ions and solvent are
      treated explicitly. This class of polymeric materials is found to exhibit rather
      distinct static and dynamic properties from linear and highly branched star
      polyelectrolyte solutions emphasized in past studies. Moderately branched
      polymers are particle-like in many of their properties, while at the same time
      they exhibit large fluctuations in size and shape as in the case of linear chain
      polymers. Correspondingly, these fluctuations suppress crystallization at high
      polymer concentrations, leading apparently to an amorphous rather than
      crystalline solid state at high polyelectrolyte concentrations. We quantify the
      onset of this transition by measuring the polymer size and shape fluctuations of
      our model star polyelectrolytes and the static and dynamic structure factor of
      these solutions over a wide range of polyelectrolyte concentration. Our findings
      for star polyelectrolytes are similar to those of polymer-grafted nanoparticles
      having a moderate grafting density, which is natural given the soft and highly
      deformable nature of both of these "particles."

PMID- 28764358
TI  - Image potential states from the van der Waals density functional.
AB  - The image potential state is one of the fundamental surface electronic states and
      has a great relevance to many surface phenomena, but its accurate description is
      a great challenge for the semilocal density functional. Here, we use the nonlocal
      van der Waals density functional to describe the image potential states of
      graphene, graphite, and carbon nanotubes. We found that although it does not
      yield the correct image potential outside the surface, the van der Waals density
      functional improves the description of image potential states because of the
      nonlocal correlation potential. Our study demonstrates the usefulness of the van
      der Waals density functional to study the surface electronic properties.

PMID- 28764359
TI  - The dissociation and recombination rates of CH4 through the Ni(111) surface: The
      effect of lattice motion.
AB  - Methane dissociation is a prototypical system for the study of surface reaction
      dynamics. The dissociation and recombination rates of CH4 through the Ni(111)
      surface are calculated by using the quantum instanton method with an analytical
      potential energy surface. The Ni(111) lattice is treated rigidly, classically,
      and quantum mechanically so as to reveal the effect of lattice motion. The
      results demonstrate that it is the lateral displacements rather than the upward
      and downward movements of the surface nickel atoms that affect the rates a lot.
      Compared with the rigid lattice, the classical relaxation of the lattice can
      increase the rates by lowering the free energy barriers. For instance, at 300 K,
      the dissociation and recombination rates with the classical lattice exceed the
      ones with the rigid lattice by 6 and 10 orders of magnitude, respectively.
      Compared with the classical lattice, the quantum delocalization rather than the
      zero-point energy of the Ni atoms further enhances the rates by widening the
      reaction path. For instance, the dissociation rate with the quantum lattice is
      about 10 times larger than that with the classical lattice at 300 K. On the rigid
      lattice, due to the zero-point energy difference between CH4 and CD4, the kinetic
      isotope effects are larger than 1 for the dissociation process, while they are
      smaller than 1 for the recombination process. The increasing kinetic isotope
      effect with decreasing temperature demonstrates that the quantum tunneling effect
      is remarkable for the dissociation process.

PMID- 28764360
TI  - From isolated diamondoids to a van-der-Waals crystal: A theoretical and
      experimental analysis of a trishomocubane and a diamantane dimer in the gas and
      solid phase.
AB  - The electronic properties of sp2/sp3 diamondoids in the crystalline state and in
      the gas phase are presented. Apparent differences in electronic properties
      experimentally observed by resonance Raman spectroscopy in the crystalline/gas
      phase and absorption measurements in the gas phase were investigated by density
      functional theory computations. Due to a reorganization of the molecular orbitals
      in the crystalline phase, the HOMO (highest occupied molecular orbital) and LUMO
      (lowest unoccupied molecular orbital) energy gaps are lowered significantly by
      0.5 eV-1 eV. The pi -> pi* transition is responsible for large absorption in both
      gas and crystalline phases. It further causes a large increase in the Raman
      intensity of the C=C stretch vibration when excited resonantly. By resonance
      Raman spectroscopy we were able to determine the C=C bond length of the
      trishomocubane dimer to exhibit 1.33 A in the ground and 1.41 A in the excited
      state.

PMID- 28764361
TI  - Effective interactions between a pair of particles modified with tethered chains.
AB  - Using molecular dynamics, we evaluate the potential of mean force for two models
      of hybrid nanoparticles, namely, for the models with fixed and movable chain
      ligands. We also investigate the structure of segments of chains around
      nanoparticles and its change when one nanoparticle approaches the other. In the
      case of an isolated particle, we also employ a density functional theory to
      compute the segment density profiles. Moreover, to determine the structure of
      segments around a core, we have employed the concept of the so-called mass
      dipoles.

PMID- 28764363
TI  - Nearest-neighbour distribution of distances in crystals from extended X-ray
      absorption fine structure.
AB  - Extended X-ray absorption fine structure (EXAFS) is a powerful probe of the
      distribution of nearest-neighbour distances around selected atomic species. We
      consider here the effect of vibrational disorder in crystals. The potential of
      EXAFS for the accurate evaluation of the coefficient of bond thermal expansion
      and its temperature dependence is discussed, with the aim of stimulating and
      facilitating the comparison with the results from total scattering experiments.
      The meaning of the distribution asymmetry in crystals and its connection with the
      effective potential anharmonicity and the bond expansion is quantitatively
      explored by comparing the results for a number of different systems. The extent
      of the relative atomic vibrations perpendicular to the bond direction and the
      perpendicular to parallel anisotropy are correlated with the extent of lattice
      negative thermal expansion as well as with the ionic mobility in superionic
      crystals.

PMID- 28764362
TI  - The mesoscopic membrane with proteins (MesM-P) model.
AB  - We present the Mesoscopic Membrane with Proteins (MesM-P) model, an extension of
      a previously developed elastic membrane model for mesoscale simulations of lipid
      membranes. MesM-P employs a discrete mesoscopic quasi-particle approach to model
      protein-facilitated shape and topology changes of the lipid membrane on length
      and time scales inaccessible to all-atom and quasimolecular coarse-grained
      molecular dynamics simulations. We investigate the ability of MesM-P to model the
      behavior of large lipid vesicles as a function of bound protein density. We find
      four distinct mechanisms for protein aggregation on the surface of the membrane,
      depending on membrane stiffness and protein spontaneous curvature. We also
      establish a connection between MesM-P and the results of higher resolution coarse
      grained molecular dynamics simulations.

PMID- 28764364
TI  - Vibrational self-consistent field theory using optimized curvilinear coordinates.
AB  - A vibrational SCF model is presented in which the functions forming the single
      mode functions in the product wavefunction are expressed in terms of internal
      coordinates and the coordinates used for each mode are optimized variationally.
      This model involves no approximations to the kinetic energy operator and does not
      require a Taylor-series expansion of the potential. The non-linear optimization
      of coordinates is found to give much better product wavefunctions than the
      limited variations considered in most previous applications of SCF methods to
      vibrational problems. The approach is tested using published potential energy
      surfaces for water, ammonia, and formaldehyde. Variational flexibility allowed in
      the current ansatze results in excellent zero-point energies expressed through
      single-product states and accurate fundamental transition frequencies realized by
      short configuration-interaction expansions. Fully variational optimization of
      single-product states for excited vibrational levels also is discussed. The
      highlighted methodology constitutes an excellent starting point for more
      sophisticated treatments, as the bulk characteristics of many-mode coupling are
      accounted for efficiently in terms of compact wavefunctions (as evident from the
      accurate prediction of transition frequencies).

PMID- 28764365
TI  - Perspective: A controversial benchmark system for water-oxide interfaces:
      H2O/TiO2(110).
AB  - The interaction of water with the single-crystalline rutile TiO2(110) surface has
      been the object of intense investigations with both experimental and
      computational methods. Not only is TiO2(110) widely considered the prototypical
      oxide surface, its interaction with water is also important in many applications
      where this material is used. At first, experimental measurements were hampered by
      the fact that preparation recipes for well-controlled surfaces had yet to be
      developed, but clear experimental evidence that water dissociation at defects
      including oxygen vacancies and steps emerged. For a perfect TiO2(110) surface,
      however, an intense debate has evolved whether or not water adsorbs as an intact
      molecule or if it dissociates by donating a proton to a so-called bridge-bonded
      surface oxygen atom. Computational studies agree that the energy difference
      between these two states is very small and thus depends sensitively on the
      computational setup and on the approximations used in density functional theory
      (DFT). While a recent molecular beam/STM experiment [Z.-T. Wang et al., Proc.
      Natl. Acad. Sci. U. S. A. 114(8), 1801-1805 (2017)] gives conclusive evidence for
      a slight preference (0.035 eV) for molecular water and a small activation energy
      of (0.36 eV) for dissociation, understanding the interface between liquid water
      and TiO2(110) arises as the next controversial frontier.

PMID- 28764366
TI  - Surface structures and compositions of Au-Rh bimetallic nanoclusters supported on
      thin-film Al2O3/NiAl(100) probed with CO.
AB  - The surface structures and compositions of Au-Rh bimetallic nanoclusters on an
      ordered thin film of Al2O3/NiAl(100) were investigated, primarily with infrared
      reflection absorption spectra and temperature-programmed desorption of CO as a
      probe molecule under ultrahigh-vacuum conditions and calculations based on
      density-functional theory. The bimetallic clusters were formed by sequential
      deposition of vapors of Au and Rh onto Al2O3/NiAl(100) at 300 K. Alloying in the
      clusters was active and proceeded toward a specific structure-a fcc phase, (100)
      orientation, and Rh core-Au shell structure, regardless of the order of metal
      deposition. For Au clusters incorporating deposited Rh, the Au atoms remained at
      the cluster surface through position exchange and became less coordinated; for
      deposition in reverse order, deposited Au simply decorated the surfaces of Rh
      clusters. Both adsorption energy and infrared absorption intensity were enhanced
      for CO on Au sites of the bimetallic clusters; both of them are associated with
      the bonding to Rh and also a decreased coordination number of CO-binding Au.
      These enhancements can thus serve as a fingerprint for alloying and atomic inter
      diffusion in similar bimetallic systems.

PMID- 28764367
TI  - Full-dimensional multi-state simulation of the photodissociation of thioanisole.
AB  - The photodissociation of thioanisole is very interesting because the experiments
      of Lim and Kim provide evidence for mode-specific effects on the product
      distribution. They showed that, with a specific S-CH3 stretching mode being
      excited as the reagent is excited to the S1 electronic state, there is a sharp
      increase in the proportion of the ground-state product to the excited-state
      product. In the present work, we report 78 011 full-dimensional semiclassical
      multi-state trajectories of the photodissociation process using the coherent
      switching with decay of mixing dynamics method. The potential surfaces and
      couplings are based on electronic structure calculations that include dynamic
      correlation through second order perturbation theory. We report results for four
      sets of initial conditions, one corresponding roughly to 0-0 excitation and three
      corresponding to exciting one vibrational mode, to look for mode-specific
      effects. The simulations show no significant mode-specific effect on the product
      energy distributions, but they do show an effect on the distribution of minimum
      energy gaps in the trajectories and on the lifetime for dissociation. In
      particular, excitation of the S-CH3 stretching mode leads to trajectories passing
      closer to the S1-S2 conical intersection and to shorter lifetimes. This provides
      a possible explanation of why experimental results are different for excitation
      of this vibration.

PMID- 28764368
TI  - 2D-3D transition in Cu-TiS2 system.
AB  - The phase diagram of the quasi-binary Cu-TiS2 system has been studied in situ in
      the temperature-concentration plane for the first time. Phase transitions between
      2D (layered) and 3D (cubic) phases in CuxTiS2 (x = 0-0.5) intercalation compounds
      have been studied by the X-ray diffraction technique in the temperature range 20
      1000  degrees C. It has been found that the stability of the layered phase is
      determined by the distribution of copper atoms between the octahedral and
      tetrahedral crystallographic sites. The occupation of octahedral sites dominates
      at low temperatures. Upon heating, tetrahedral site occupation is limited due to
      elastic lattice distortion and the layered phase becomes unstable and transforms
      to the spinel. Further heating allows the distribution of copper between
      octahedral and tetrahedral sites; the layered phase becomes stable again.

PMID- 28764369
TI  - Structural and dynamic characteristics in monolayer square ice.
AB  - When water is constrained between two sheets of graphene, it becomes an
      intriguing monolayer solid with a square pattern due to the ultrahigh van der
      Waals pressure. However, the square ice phase has become a matter of debate due
      to the insufficient experimental interpretation and the slightly rhomboidal
      feature in simulated monolayer square-like structures. Here, we performed
      classical molecular dynamics simulations to reveal monolayer square ice in
      graphene nanocapillaries from the perspective of structure and dynamic
      characteristics. Monolayer square-like ice (instantaneous snapshot), assembled
      square-rhombic units with stacking faults, is a long-range ordered structure, in
      which the square and rhombic units are assembled in an order of alternative
      distribution, and the other rhombic unit forms stacking faults (polarized water
      chains). Spontaneous flipping of water molecules in monolayer square-like ice is
      intrinsic and induces transformations among different elementary units, resulting
      in the structural evolution of monolayer square ice in dynamics. The existence of
      stacking faults should be attributed to the spontaneous flipping behavior of
      water molecules under ambient temperature. Statistical averaging results (thermal
      average positions) demonstrate the inherent square characteristic of monolayer
      square ice. The simulated data and insight obtained here might be significant for
      understanding the topological structure and dynamic behavior of monolayer square
      ice.

PMID- 28764370
TI  - Hydrogen bonding and vibrational energy relaxation of interfacial water: A full
      DFT molecular dynamics simulation.
AB  - The air-water interface has been a subject of extensive theoretical and
      experimental studies due to its ubiquity in nature and its importance as a model
      system for aqueous hydrophobic interfaces. We report on the structure and
      vibrational energy transfer dynamics of this interfacial water system studied
      with equilibrium and non-equilibrium molecular dynamics simulations employing a
      density functional theory -based description of the system and the kinetic energy
      spectral density analysis. The interfacial water molecules are found to make
      fewer and weaker hydrogen (H)-bonds on average compared to those in the bulk. We
      also find that (i) the H-bonded OH groups conjugate to the free OH exhibit rather
      low vibrational frequencies (3000-3500 cm-1); (ii) the presence of a significant
      fraction (>10%) of free and randomly oriented water molecules at the interface
      ("labile water"), neither of whose OH groups are strong H-bond donors; (iii) the
      inertial rotation of free OH groups, especially from the labile water, contribute
      to the population decay of excited free OH groups with comparable rate and
      magnitude as intramolecular energy transfer between the OH groups. These results
      suggest that the labile water, which might not be easily detectable by the
      conventional vibrational sum frequency generation method, plays an important role
      in the surface water dynamics.

PMID- 28764371
TI  - Toward reliable modeling of S-nitrosothiol chemistry: Structure and properties of
      methyl thionitrite (CH3SNO), an S-nitrosocysteine model.
AB  - Methyl thionitrite CH3SNO is an important model of S-nitrosated cysteine
      aminoacid residue (CysNO), a ubiquitous biological S-nitrosothiol (RSNO) involved
      in numerous physiological processes. As such, CH3SNO can provide insights into
      the intrinsic properties of the -SNO group in CysNO, in particular, its weak and
      labile S-N bond. Here, we report an ab initio computational investigation of the
      structure and properties of CH3SNO using a composite Feller-Peterson-Dixon scheme
      based on the explicitly correlated coupled cluster with single, double, and
      perturbative triple excitations calculations extrapolated to the complete basis
      set limit, CCSD(T)-F12/CBS, with a number of additive corrections for the effects
      of quadruple excitations, core-valence correlation, scalar-relativistic and spin
      orbit effects, as well as harmonic zero-point vibrational energy with an
      anharmonicity correction. These calculations suggest that the S-N bond in CH3SNO
      is significantly elongated (1.814 A) and has low stretching frequency and
      dissociation energy values, nuS-N = 387 cm-1 and D0 = 32.4 kcal/mol. At the same
      time, the S-N bond has a sizable rotation barrier, ?E0? = 12.7 kcal/mol, so
      CH3SNO exists as a cis- or trans-conformer, the latter slightly higher in energy,
      ?E0 = 1.2 kcal/mol. The S-N bond properties are consistent with the antagonistic
      nature of CH3SNO, whose resonance representation requires two chemically opposite
      (antagonistic) resonance structures, CH3-S+=N-O- and CH3-S-/NO+, which can be
      probed using external electric fields and quantified using the natural resonance
      theory approach (NRT). The calculated S-N bond properties slowly converge with
      the level of correlation treatment, with the recently developed distinguished
      cluster with single and double excitations approximation (DCSD-F12) performing
      significantly better than the coupled cluster with single and double excitations
      (CCSD-F12), although still inferior to the CCSD(T)-F12 method that includes
      perturbative triple excitations. Double-hybrid density functional theory (DFT)
      calculations with mPW2PLYPD/def2-TZVPPD reproduce well the geometry, vibrational
      frequencies, and the S-N bond rotational barrier in CH3SNO, while hybrid DFT
      calculations with PBE0/def2-TZVPPD give a better S-N bond dissociation energy.

PMID- 28764372
TI  - Influence of sample preparation on the transformation of low-density to high
      density amorphous ice: An explanation based on the potential energy landscape.
AB  - Experiments and computer simulations of the transformations of amorphous ices
      display different behaviors depending on sample preparation methods and on the
      rates of change of temperature and pressure to which samples are subjected. In
      addition to these factors, simulation results also depend strongly on the chosen
      water model. Using computer simulations of the ST2 water model, we study how the
      sharpness of the compression-induced transition from low-density amorphous ice
      (LDA) to high-density amorphous ice (HDA) is influenced by the preparation of
      LDA. By studying LDA samples prepared using widely different procedures, we find
      that the sharpness of the LDA-to-HDA transformation is correlated with the depth
      of the initial LDA sample in the potential energy landscape (PEL), as
      characterized by the inherent structure energy. Our results show that the complex
      phenomenology of the amorphous ices reported in experiments and computer
      simulations can be understood and predicted in a unified way from knowledge of
      the PEL of the system.

PMID- 28764373
TI  - An extended E?e Jahn-Teller Hamiltonian for large-amplitude motion: Application
      to vibrational conical intersections in CH3SH and CH3OH.
AB  - An extended E?e Jahn-Teller Hamiltonian is presented for the case where the
      (slow) nuclear motion extends far from the symmetry point and may be described
      approximately as motion on a sphere. Rather than the traditional power series
      expansion in the displacement from the C3v symmetry point, an expansion in the
      spherical harmonics is employed. Application is made to the vibrational Jahn
      Teller effect in CH3XH, with X = S, O, where the equilibrium CXH angles are 83
      degrees  and 72 degrees , respectively. In addition to the symmetry-required
      conical intersection (CI) at the C3v symmetry point, ab initio calculations
      reveal sets of six symmetry-allowed vibrational CIs in each molecule. The CIs for
      each molecule are arranged differently in the large-amplitude space, and that
      difference is reflected in the infrared spectra. The CIs in CH3SH are found in
      both eclipsed and staggered geometries, whereas those for CH3OH are found only in
      the eclipsed geometry near the torsional saddle point. This difference between
      the two molecules is reflected in the respective high-resolution spectra in the
      CH stretch fundamental region.

PMID- 28764374
TI  - Properties of the water to boron nitride interaction: From zero to two dimensions
      with benchmark accuracy.
AB  - Molecular adsorption on surfaces plays an important part in catalysis, corrosion,
      desalination, and various other processes that are relevant to industry and in
      nature. As a complement to experiments, accurate adsorption energies can be
      obtained using various sophisticated electronic structure methods that can now be
      applied to periodic systems. The adsorption energy of water on boron nitride
      substrates, going from zero to 2-dimensional periodicity, is particularly
      interesting as it calls for an accurate treatment of polarizable electrostatics
      and dispersion interactions, as well as posing a practical challenge to
      experiments and electronic structure methods. Here, we present reference
      adsorption energies, static polarizabilities, and dynamic polarizabilities, for
      water on BN substrates of varying size and dimension. Adsorption energies are
      computed with coupled cluster theory, fixed-node quantum Monte Carlo (FNQMC), the
      random phase approximation, and second order Moller-Plesset theory. These
      wavefunction based correlated methods are found to agree in molecular as well as
      periodic systems. The best estimate of the water/h-BN adsorption energy is -107+/
      7 meV from FNQMC. In addition, the water adsorption energy on the BN substrates
      could be expected to grow monotonically with the size of the substrate due to
      increased dispersion interactions, but interestingly, this is not the case here.
      This peculiar finding is explained using the static polarizabilities and
      molecular dispersion coefficients of the systems, as computed from time-dependent
      density functional theory (DFT). Dynamic as well as static polarizabilities are
      found to be highly anisotropic in these systems. In addition, the many-body
      dispersion method in DFT emerges as a particularly useful estimation of finite
      size effects for other expensive, many-body wavefunction based methods.

PMID- 28764375
TI  - Real-time visualization of the vibrational wavepacket dynamics in electronically
      excited pyrimidine via femtosecond time-resolved photoelectron imaging.
AB  - The vibrational wavepacket dynamics at the very early stages of the S1-T1
      intersystem crossing in photoexcited pyrimidine is visualized in real time by
      femtosecond time-resolved photoelectron imaging and time-resolved mass
      spectroscopy. A coherent superposition of the vibrational states is prepared by
      the femtosecond pump pulse at 315.3 nm, resulting in a vibrational wavepacket.
      The composition of the prepared wavepacket is directly identified by a sustained
      quantum beat superimposed on the parent-ion transient, possessing a frequency in
      accord with the energy separation between the 6a1 and 6b2 states. The dephasing
      time of the vibrational wavepacket is determined to be 82 ps. More importantly,
      the variable Franck-Condon factors between the wavepacket components and the
      dispersed cation vibrational levels are experimentally illustrated to identify
      the dark state and follow the energy-flow dynamics on the femtosecond time scale.
      The time-dependent intensities of the photoelectron peaks originated from the 6a1
      vibrational state exhibit a clear quantum beating pattern with similar
      periodicity but a phase shift of pi rad with respect to those from the 6b2 state,
      offering an unambiguous picture of the restricted intramolecular vibrational
      energy redistribution dynamics in the 6a1/6b2 Fermi resonance.

PMID- 28764376
TI  - Characteristic features of the Shannon information entropy of dipolar Bose
      Einstein condensates.
AB  - Calculation of the Shannon information entropy (S) and its connection with the
      order-disorder transition and with inter-particle interaction provide a
      challenging research area in the field of quantum information. Experimental
      progress with cold trapped atoms has corroborated this interest. In the present
      work, S is calculated for the Bose-Einstein condensate (BEC) with dominant
      dipolar interaction for different dipole strengths, trap aspect ratios, and
      number of particles (N). Trapped dipolar bosons in an anisotropic trap provide an
      example of a system where the effective interaction is strongly determined by the
      trap geometry. The main conclusion of the present calculation is that the
      anisotropic trap reduces the number of degrees of freedom, resulting in more
      ordered configurations. Landsberg's order parameter exhibits quick saturation
      with the increase in scattering length in both prolate and oblate traps. We also
      define the threshold scattering length which makes the system completely
      disordered. Unlike non-dipolar BEC in a spherical trap, we do not find a
      universal linear relation between S and lnN, and we, therefore, introduce a
      general quintic polynomial fit rather well working for a wide range of particle
      numbers.

PMID- 28764377
TI  - Entropic elasticity and dynamics of the bacterial chromosome: A simulation study.
AB  - We study the compression and extension dynamics of a DNA-like polymer interacting
      with non-DNA binding and DNA-binding proteins, by means of computer simulations.
      The geometry we consider is inspired by recent experiments probing the
      compressional elasticity of the bacterial nucleoid (DNA plus associated
      proteins), where DNA is confined into a cylindrical container and subjected to
      the action of a "piston"-a spherical bead to which an external force is applied.
      We quantify the effect of steric interactions (excluded volume) on the force
      extension curves as the polymer is compressed. We find that non-DNA-binding
      proteins, even at low densities, exert an osmotic force which can be a lot larger
      than the entropic force exerted by the compressed DNA. The trends we observe are
      qualitatively robust with respect to changes in protein sizes and are similar for
      neutral and charged proteins (and DNA). We also quantify the dynamics of DNA
      expansion following removal of the "piston": while the expansion is well fitted
      by power laws, the apparent exponent depends on protein concentration and protein
      DNA interaction in a significant way. We further highlight an interesting kinetic
      process which we observe during the expansion of DNA interacting with DNA-binding
      proteins when the interaction strength is intermediate: the proteins bind while
      the DNA is packaged by the compression force, but they "pop-off" one-by-one as
      the force is removed, leading to a slow unzipping kinetics. Finally, we quantify
      the importance of supercoiling, which is an important feature of bacterial DNA in
      vivo.

PMID- 28764378
TI  - Molecular simulations of self-assembly processes in metal-organic frameworks:
      Model dependence.
AB  - Molecular simulation is a powerful tool for investigating microscopic behavior in
      various chemical systems, where the use of suitable models is critical to
      successfully reproduce the structural and dynamic properties of the real systems
      of interest. In this context, molecular dynamics simulation studies of self
      assembly processes in metal-organic frameworks (MOFs), a well-known class of
      porous materials with interesting chemical and physical properties, are
      relatively challenging, where a reasonably accurate representation of metal
      ligand interactions is anticipated to play an important role. In the current
      study, we both investigate the performance of some existing models and introduce
      and test new models to help explore the self-assembly in an archetypal Zn
      carboxylate MOF system. To this end, the behavior of six different Zn-ion models,
      three solvent models, and two ligand models was examined and validated against
      key experimental structural parameters. To explore longer time scale ordering
      events during MOF self-assembly via explicit solvent simulations, it is necessary
      to identify a suitable combination of simplified model components representing
      metal ions, organic ligands, and solvent molecules. It was observed that an
      extended cationic dummy atom (ECDA) Zn-ion model combined with an all-atom
      carboxylate ligand model and a simple dipolar solvent model can reproduce
      characteristic experimental structures for the archetypal MOF system. The
      successful use of these models in extensive sets of molecular simulations, which
      provide key insights into the self-assembly mechanism of this archetypal MOF
      system occurring during the early stages of this process, has been very recently
      reported.

PMID- 28764379
TI  - Communication: Development of standing evanescent-wave fluorescence correlation
      spectroscopy and its application to the lateral diffusion of lipids in a
      supported lipid bilayer.
AB  - We present standing evanescent-wave fluorescence correlation spectroscopy (SEW
      FCS). This technique utilizes the interference of two evanescent waves which
      generates a standing evanescent-wave. Fringe-pattern illumination created by a
      standing evanescent-wave enables us to measure the diffusion coefficients of
      molecules with a super-resolution corresponding to one fringe width. Because the
      fringe width can be reliably estimated by a simple procedure, utilization of
      fringes is beneficial to quantitatively analyze the slow diffusion of molecules
      in a supported lipid bilayer (SLB), a model biomembrane formed on a solid
      substrate, with the timescale relevant for reliable FCS analysis. Furthermore,
      comparison of the data between SEW-FCS and conventional total-internal reflection
      FCS, which can also be performed by the SEW-FCS instrument, effectively
      eliminates the artifact due to afterpulsing of the photodiode detector. The
      versatility of SEW-FCS is demonstrated by its application to various SLBs.

PMID- 28764381
TI  - Publisher's Note: "Pure-rotational H2 thermometry by ultrabroadband coherent anti
      Stokes Raman spectroscopy" [J. Chem. Phys. 146, 224202 (2017)].

PMID- 28764380
TI  - Extending the range and physical accuracy of coarse-grained models: Order
      parameter dependent interactions.
AB  - Order parameters (i.e., collective variables) are often used to describe the
      behavior of systems as they capture different features of the free energy
      surface. Yet, most coarse-grained (CG) models only employ two- or three-body non
      bonded interactions between the CG particles. In situations where these
      interactions are insufficient for the CG model to reproduce the structural
      distributions of the underlying fine-grained (FG) model, additional interactions
      must be included. In this paper, we introduce an approach to expand the basis
      sets available in the multiscale coarse-graining (MS-CG) methodology by including
      order parameters. Then, we investigate the ability of an additive local order
      parameter (e.g., density) and an additive global order parameter (i.e., distance
      from a hard wall) to improve the description of CG models in interfacial systems.
      Specifically, we study methanol liquid-vapor coexistence, acetonitrile liquid
      vapor coexistence, and acetonitrile liquid confined by hard-wall plates, all
      using single site CG models. We find that the use of order parameters
      dramatically improves the reproduction of structural properties of interfacial CG
      systems relative to the FG reference as compared with pairwise CG interactions
      alone.

PMID- 28764382
TI  - Multi-state trajectory approach to non-adiabatic dynamics: General formalism and
      the active state trajectory approximation.
AB  - A general theoretical framework is derived for the recently developed multi-state
      trajectory (MST) approach from the time dependent Schrodinger equation, resulting
      in equations of motion for coupled nuclear-electronic dynamics equivalent to
      Hamilton dynamics or Heisenberg equation based on a new multistate Meyer-Miller
      (MM) model. The derived MST formalism incorporates both diabatic and adiabatic
      representations as limiting cases and reduces to Ehrenfest or Born-Oppenheimer
      dynamics in the mean-field or the single-state limits, respectively. In the
      general multistate formalism, nuclear dynamics is represented in terms of a set
      of individual state-specific trajectories, while in the active state trajectory
      (AST) approximation, only one single nuclear trajectory on the active state is
      propagated with its augmented images running on all other states. The AST
      approximation combines the advantages of consistent nuclear-coupled electronic
      dynamics in the MM model and the single nuclear trajectory in the trajectory
      surface hopping (TSH) treatment and therefore may provide a potential alternative
      to both Ehrenfest and TSH methods. The resulting algorithm features in a
      consistent description of coupled electronic-nuclear dynamics and excellent
      numerical stability. The implementation of the MST approach to several benchmark
      systems involving multiple nonadiabatic transitions and conical intersection
      shows reasonably good agreement with exact quantum calculations, and the results
      in both representations are similar in accuracy. The AST treatment also
      reproduces the exact results reasonably, sometimes even quantitatively well, with
      a better performance in the adiabatic representation.

PMID- 28764383
TI  - A unified ab initio approach to the correlated quantum dynamics of ultracold
      fermionic and bosonic mixtures.
AB  - We extent the recently developed Multi-Layer Multi-Configuration Time-Dependent
      Hartree method for Bosons for simulating the correlated quantum dynamics of
      bosonic mixtures to the fermionic sector and establish a unifying approach for
      the investigation of the correlated quantum dynamics of a mixture of
      indistinguishable particles, be it fermions or bosons. Relying on a multi-layer
      wave-function expansion, the resulting Multi-Layer Multi-Configuration Time
      Dependent Hartree method for Mixtures (ML-MCTDHX) can be adapted to efficiently
      resolve system-specific intra- and inter-species correlations. The versatility
      and efficiency of ML-MCTDHX are demonstrated by applying it to the problem of
      colliding few-atom mixtures of both Bose-Fermi and Fermi-Fermi types. Thereby, we
      elucidate the role of correlations in the transmission and reflection properties
      of the collisional events. In particular, we present examples where the
      reflection (transmission) at the other atomic species is a correlation-dominated
      effect, i.e., it is suppressed in the mean-field approximation.

PMID- 28764384
TI  - Identification of crystalline structures in jet-cooled acetylene large clusters
      studied by two-dimensional correlation infrared spectroscopy.
AB  - We investigated the crystalline structures of jet-cooled acetylene (C2H2) large
      clusters by laser spectroscopy and chemometrics. The CH stretching vibrations of
      the C2H2 large clusters were observed by infrared (IR) cavity ringdown
      spectroscopy. The IR spectra of C2H2 clusters were measured under the conditions
      of various concentrations of C2H2/He mixture gas for supersonic jets. Upon
      increasing the gas concentration from 1% to 10%, we observed a rapid intensity
      enhancement for a band in the IR spectra. The strong dependence of the intensity
      on the gas concentration indicates that the band was assigned to CH stretching
      vibrations of the large clusters. An analysis of the IR spectra by two
      dimensional correlation spectroscopy revealed that the IR absorption due to the
      C2H2 large cluster is decomposed into two CH stretching vibrations. The
      vibrational frequencies of the two bands are almost equivalent to the IR
      absorption of the pure- and poly-crystalline orthorhombic structures in the
      aerosol particles. The characteristic temperature behavior of the IR spectra
      implies the existence of the other large cluster, which is discussed in terms of
      the phase transition of a bulk crystal.

PMID- 28764385
TI  - Impact of dispersion forces on the atomic structure of a prototypical network
      forming disordered system: The case of liquid GeSe2.
AB  - A set of structural properties of liquid GeSe2 are calculated by using first
      principles molecular dynamics and including, for the first time, van der Waals
      dispersion forces. None of the numerous atomic-scale simulations performed in the
      past on this prototypical disordered network-forming material had ever accounted
      for dispersion forces in the expression of the total energy. For this purpose, we
      employed either the Grimme-D2 or the maximally localized Wannier function scheme.
      We assessed the impact of dispersion forces on properties such as partial
      structure factors, pair correlation functions, bond angle distribution, and
      number of corner vs edge sharing connections. The maximally localized Wannier
      function scheme is more reliable than the Grimme-D2 scheme in reproducing
      existing first-principles results. In particular, the Grimme-D2 scheme worsens
      the agreement with experiments in the case of the Ge-Ge pair correlation
      function. Our study shows that the impact of dispersion forces on disordered
      chalcogenides has to be considered with great care since it cannot be necessarily
      the same when adopting different recipes.

PMID- 28764386
TI  - The long persistence length of model tubules.
AB  - Young's elastic modulus and the persistence length are calculated for a coarse
      grained model of tubule forming polymers. The model uses a wedge shaped composite
      of particles that previously has been shown to self-assemble into tubules. These
      calculations demonstrate that the model yields very large persistence lengths
      (corresponding to 78-126 MUm) that are comparable to that observed in experiments
      for the microtubule lengths accessible to the calculations. The source for the
      stiffness is the restricted rotation of the monomer due to the excluded volume
      interactions between bonded macromolecular monomers as well as the binding
      between monomers. For this reason, large persistence lengths are common in tubule
      systems with a macromolecule as the monomer. The persistence length increases
      linearly with increased binding strength in the filament direction. No dependence
      in the persistence length is found for varying the tubule pitch for geometries
      with the protofilaments remaining straight.

PMID- 28764387
TI  - Valence electronic structure of cobalt phthalocyanine from an optimally tuned
      range-separated hybrid functional.
AB  - We analyse the valence electronic structure of cobalt phthalocyanine (CoPc) by
      means of optimally tuning a range-separated hybrid functional. The tuning is
      performed by modifying both the amount of short-range exact exchange (alpha)
      included in the hybrid functional and the range-separation parameter (gamma),
      with two strategies employed for finding the optimal gamma for each alpha. The
      influence of these two parameters on the structural, electronic, and magnetic
      properties of CoPc is thoroughly investigated. The electronic structure is found
      to be very sensitive to the amount and range in which the exact exchange is
      included. The electronic structure obtained using the optimal parameters is
      compared to gas-phase photo-electron data and GW calculations, with the
      unoccupied states additionally compared with inverse photo-electron spectroscopy
      measurements. The calculated spectrum with tuned gamma, determined for the
      optimal value of alpha = 0.1, yields a very good agreement with both experimental
      results and with GW calculations that well-reproduce the experimental data.

PMID- 28764389
TI  - Erratum: "Reaction rates and kinetic isotope effects of H2 + OH -> H2O + H" [J.
      Chem. Phys. 144, 174303 (2016)].

PMID- 28764388
TI  - Path lumping: An efficient algorithm to identify metastable path channels for
      conformational dynamics of multi-body systems.
AB  - Constructing Markov state models from large-scale molecular dynamics simulation
      trajectories is a promising approach to dissect the kinetic mechanisms of complex
      chemical and biological processes. Combined with transition path theory, Markov
      state models can be applied to identify all pathways connecting any
      conformational states of interest. However, the identified pathways can be too
      complex to comprehend, especially for multi-body processes where numerous
      parallel pathways with comparable flux probability often coexist. Here, we have
      developed a path lumping method to group these parallel pathways into metastable
      path channels for analysis. We define the similarity between two pathways as the
      intercrossing flux between them and then apply the spectral clustering algorithm
      to lump these pathways into groups. We demonstrate the power of our method by
      applying it to two systems: a 2D-potential consisting of four metastable energy
      channels and the hydrophobic collapse process of two hydrophobic molecules. In
      both cases, our algorithm successfully reveals the metastable path channels. We
      expect this path lumping algorithm to be a promising tool for revealing
      unprecedented insights into the kinetic mechanisms of complex multi-body
      processes.

PMID- 28764390
TI  - Ab initio multiple spawning dynamics study of dimethylnitramine and
      dimethylnitramine-Fe complex to model their ultrafast nonadiabatic chemistry.
AB  - Conical intersections are now firmly established to be the key features in the
      excited electronic state processes of polyatomic energetic molecules. In the
      present work, we have explored conical intersection-mediated nonadiabatic
      chemical dynamics of a simple analogue nitramine molecule, dimethylnitramine
      (DMNA, containing one N-NO2 energetic group), and its complex with an iron atom
      (DMNA-Fe). For this task, we have used the ab initio multiple spawning (AIMS)
      dynamics simulation at the state averaged-complete active space self-consistent
      field(8,5)/6-31G(d) level of theory. We have found that DMNA relaxes back to the
      ground (S0) state following electronic excitation to the S1 excited state [which
      is an (n,pi*) excited state] with a time constant of approximately 40 fs. This
      AIMS result is in very good agreement with the previous surface hopping-result
      and femtosecond laser spectroscopy result. DMNA does not dissociate during this
      fast internal conversion from the S1 to the S0 state. DMNA-Fe also undergoes
      extremely fast relaxation from the upper S1 state to the S0 state; however, this
      relaxation pathway is dissociative in nature. DMNA-Fe undergoes initial Fe-O, N
      O, and N-N bond dissociations during relaxation from the upper S1 state to the
      ground S0 state through the respective conical intersection. The AIMS simulation
      reveals the branching ratio of these three channels as N-N:Fe-O:N-O = 6:3:1
      (based on 100 independent simulations). Furthermore, the AIMS simulation reveals
      that the Fe-O bond dissociation channel exhibits the fastest (time constant 24
      fs) relaxation, while the N-N bond dissociation pathway features the slowest
      (time constant 128 fs) relaxation. An intermediate time constant (30 fs) is found
      for the N-O bond dissociation channel. This is the first nonadiabatic chemical
      dynamics study of metal-contained energetic molecules through conical
      intersections.

PMID- 28764391
TI  - Efficient orientational averaging of nonlinear optical signals in multi
      chromophore systems.
AB  - The simulation of nonlinear optical signals measured in isotropic media requires
      averaging over the orientations of the chromophores. Herein, we discuss the
      evaluation of orientationally averaged four-wave-mixing, six-wave-mixing, etc.,
      signals in terms of contracted transition dipole moment operators, which were
      introduced earlier for the orientational averaging of linear absorption signals.
      We demonstrate that the contracted transition dipole moment operators
      substantially facilitate the orientational averaging of nonlinear signals in
      multi-chromophore systems. We consider both the perturbative evaluation of
      signals (through nonlinear response functions) as well as the nonperturbative
      evaluation (through the numerical calculation of the nonlinear polarization of
      driven systems).

PMID- 28764392
TI  - The pacemaker role of thalamic reticular nucleus in controlling spike-wave
      discharges and spindles.
AB  - Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be
      caused by pathological interactions within the thalamocortical system. Cortical
      spindling oscillations are also demonstrated to involve the oscillatory
      thalamocortical rhythms generated by the synaptic circuitry of the thalamus and
      cortex. This implies that SWDs and spindling oscillations can share the common
      thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is
      hypothesized to regulate the onsets and propagations of both the epileptic SWDs
      and sleep spindles. Based on the proposed single-compartment thalamocortical
      neural field model, we firstly investigate the stimulation effect of RE on the
      initiations, terminations, and transitions of SWDs. It is shown that the
      activations and deactivations of RE triggered by single-pulse stimuli can drive
      the cortical subsystem to behave as the experimentally observed onsets and self
      abatements of SWDs, as well as the transitions from 2-spike and wave discharges
      (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the
      specific relay nucleus (TC), rich transition behaviors in cortex can be obtained
      through the upstream projection path, RE->TC->Cortex. Although some of the
      complex dynamical patterns can be expected from the earlier single compartment
      thalamocortical model, the effect of brain network topology on the emergence of
      SWDs and spindles, as well as the transitions between them, has not been fully
      investigated. We thereby develop a spatially extended 3-compartment coupled
      network model with open-/closed-end connective configurations, to investigate the
      spatiotemporal effect of RE on the SWDs and spindles. Results show that the
      degrees of activations of RE1 can induce the rich spatiotemporal evolution
      properties including the propagations from SWDs to spindles within different
      compartments and the transitions between them, through the RE1->TC1->Cortex1 and
      Cortex1->Cortex2->Cortex3 projecting paths, respectively. Overall, those results
      imply that RE possesses the pacemaker function in controlling SWDs and spindling
      oscillations, which computationally provide causal support for the involvement of
      RE in absence seizures and sleep spindles.

PMID- 28764393
TI  - Constructing an autonomous system with infinitely many chaotic attractors.
AB  - Some classical chaotic systems such as the Lorenz system and Chua system have
      finite numbers of chaotic attractors. This letter develops a simple, effective
      method for constructing lower-dimensional autonomous systems with infinitely many
      chaotic attractors. As an application, a Lorenz-type system and a Rossler-type
      system with infinitely many chaotic attractors are constructed with bifurcation
      analysis, and with an extension to the fractional-order setting.

PMID- 28764394
TI  - On the effect of discreteness in the modulation instability for the Salerno
      model.
AB  - A Salerno model with first-and second-neighbor couplings is derived for the
      nonlinear transmission lines. We revisit the problem of modulation instability in
      the Salerno model. We derive the expression for the modulation instability gain
      and use them to explore the role of discreteness. We show that discreteness has
      an impact on the mechanism by which wave trains of soliton type can be generated
      in the Salerno model. We also show that second-neighbor couplings have an effect
      on the signal voltage.

PMID- 28764395
TI  - How close are time series to power tail Levy diffusions?
AB  - This article presents a new and easily implementable method to quantify the so
      called coupling distance between the law of a time series and the law of a
      differential equation driven by Markovian additive jump noise with heavy-tailed
      jumps, such as alpha-stable Levy flights. Coupling distances measure the
      proximity of the empirical law of the tails of the jump increments and a given
      power law distribution. In particular, they yield an upper bound for the distance
      of the respective laws on path space. We prove rates of convergence comparable to
      the rates of the central limit theorem which are confirmed by numerical
      simulations. Our method applied to a paleoclimate time series of glacial climate
      variability confirms its heavy tail behavior. In addition, this approach gives
      evidence for heavy tails in datasets of precipitable water vapor of the Western
      Tropical Pacific.

PMID- 28764396
TI  - Atypical transistor-based chaotic oscillators: Design, realization, and
      diversity.
AB  - In this paper, we show that novel autonomous chaotic oscillators based on one or
      two bipolar junction transistors and a limited number of passive components can
      be obtained via random search with suitable heuristics. Chaos is a pervasive
      occurrence in these circuits, particularly after manual adjustment of a variable
      resistor placed in series with the supply voltage source. Following this
      approach, 49 unique circuits generating chaotic signals when physically realized
      were designed, representing the largest collection of circuits of this kind to
      date. These circuits are atypical as they do not trivially map onto known
      topologies or variations thereof. They feature diverse spectra and predominantly
      anti-persistent monofractal dynamics. Notably, we recurrently found a circuit
      comprising one resistor, one transistor, two inductors, and one capacitor, which
      generates a range of attractors depending on the parameter values. We also found
      a circuit yielding an irregular quantized spike-train resembling some aspects of
      neural discharge and another one generating a double-scroll attractor, which
      represent the smallest known transistor-based embodiments of these behaviors.
      Through three representative examples, we additionally show that diffusive
      coupling of heterogeneous oscillators of this kind may give rise to complex
      entrainment, such as lag synchronization with directed information transfer and
      generalized synchronization. The replicability and reproducibility of the
      experimental findings are good.

PMID- 28764397
TI  - Achieving control and synchronization merely through a stochastically adaptive
      feedback coupling.
AB  - Techniques of deterministically adaptive feedback couplings have been
      successfully and extensively applied to realize control or/and synchronization in
      chaotic dynamical systems and even in complex dynamical networks. In this
      article, a technique of stochastically adaptive feedback coupling is novelly
      proposed to not only realize control in chaotic dynamical systems but also
      achieve synchronization in unidirectionally coupled systems. Compared with those
      deterministically adaptive couplings, the proposed stochastic technique
      interestingly shows some advantages from a physical viewpoint of time and energy
      consumptions. More significantly, the usefulness of the proposed stochastic
      technique is analytically validated by the theory of stochastic processes. It is
      anticipated that the proposed stochastic technique will be widely used in
      achieving system control and network synchronization.

PMID- 28764398
TI  - A universal order parameter for synchrony in networks of limit cycle oscillators.
AB  - We analyze the properties of order parameters measuring synchronization and phase
      locking in complex oscillator networks. First, we review network order parameters
      previously introduced and reveal several shortcomings: none of the introduced
      order parameters capture all transitions from incoherence over phase locking to
      full synchrony for arbitrary, finite networks. We then introduce an alternative,
      universal order parameter that accurately tracks the degree of partial phase
      locking and synchronization, adapting the traditional definition to account for
      the network topology and its influence on the phase coherence of the oscillators.
      We rigorously prove that this order parameter is strictly monotonously increasing
      with the coupling strength in the phase locked state, directly reflecting the
      dynamic stability of the network. Furthermore, it indicates the onset of full
      phase locking by a diverging slope at the critical coupling strength. The order
      parameter may find applications across systems where different types of synchrony
      are possible, including biological networks and power grids.

PMID- 28764399
TI  - Fire, ice, water, and dirt: A simple climate model.
AB  - A simple paleoclimate model was developed as a modeling exercise. The model is a
      lumped parameter system consisting of an ocean (water), land (dirt), glacier, and
      sea ice (ice) and driven by the sun (fire). In comparison with other such models,
      its uniqueness lies in its relative simplicity yet yielding good results. For
      nominal values of parameters, the system is very sensitive to small changes in
      the parameters, yielding equilibrium, steady oscillations, and catastrophes such
      as freezing or boiling oceans. However, stable solutions can be found, especially
      naturally oscillating solutions. For nominally realistic conditions, natural
      periods of order 100kyrs are obtained, and chaos ensues if the Milankovitch
      orbital forcing is applied. An analysis of a truncated system shows that the
      naturally oscillating solution is a limit cycle with the characteristics of a
      relaxation oscillation in the two major dependent variables, the ocean
      temperature and the glacier ice extent. The key to getting oscillations is having
      the effective emissivity decreasing with temperature and, at the same time, the
      effective ocean albedo decreases with increasing glacier extent. Results of the
      original model compare favorably to the proxy data for ice mass variation, but
      not for temperature variation. However, modifications to the effective emissivity
      and albedo can be made to yield much more realistic results. The primary
      conclusion is that the opinion of Saltzman [Clim. Dyn. 5, 67-78 (1990)] is
      plausible that the external Milankovitch orbital forcing is not sufficient to
      explain the dominant 100kyr period in the data.

PMID- 28764400
TI  - Chimera states in a multilayer network of coupled and uncoupled neurons.
AB  - We study the emergence of chimera states in a multilayer neuronal network, where
      one layer is composed of coupled and the other layer of uncoupled neurons.
      Through the multilayer structure, the layer with coupled neurons acts as the
      medium by means of which neurons in the uncoupled layer share information in
      spite of the absence of physical connections among them. Neurons in the coupled
      layer are connected with electrical synapses, while across the two layers,
      neurons are connected through chemical synapses. In both layers, the dynamics of
      each neuron is described by the Hindmarsh-Rose square wave bursting dynamics. We
      show that the presence of two different types of connecting synapses within and
      between the two layers, together with the multilayer network structure, plays a
      key role in the emergence of between-layer synchronous chimera states and
      patterns of synchronous clusters. In particular, we find that these chimera
      states can emerge in the coupled layer regardless of the range of electrical
      synapses. Even in all-to-all and nearest-neighbor coupling within the coupled
      layer, we observe qualitatively identical between-layer chimera states. Moreover,
      we show that the role of information transmission delay between the two layers
      must not be neglected, and we obtain precise parameter bounds at which chimera
      states can be observed. The expansion of the chimera region and annihilation of
      cluster and fully coherent states in the parameter plane for increasing values of
      inter-layer chemical synaptic time delay are illustrated using effective range
      measurements. These results are discussed in the light of neuronal evolution,
      where the coexistence of coherent and incoherent dynamics during the
      developmental stage is particularly likely.

PMID- 28764401
TI  - Analytical study of funnel type Rossler attractor.
AB  - We investigate the behavior of a typical trajectory in a funnel type Rossler
      attractor. Using a suitable averaging method, we propose to describe the
      originally more difficult time-continuous chaotic behavior of the system using an
      approximate four-parameter surrogate iteration scheme. This approach has the
      merits of helping one see more easily how the height of the peaks and the peak-to
      peak durations vary as one tunes the system parameters. Our analytical results
      compare favorably well with those obtained through the numerical integration of
      the system.

PMID- 28764403
TI  - Fractal stock markets: International evidence of dynamical (in)efficiency.
AB  - The last systemic financial crisis has reawakened the debate on the efficient
      nature of financial markets, traditionally described as semimartingales. The
      standard approaches to endow the general notion of efficiency of an empirical
      content turned out to be somewhat inconclusive and misleading. We propose a
      topological-based approach to quantify the informational efficiency of a
      financial time series. The idea is to measure the efficiency by means of the
      pointwise regularity of a (stochastic) function, given that the signature of a
      martingale is that its pointwise regularity equals 12. We provide estimates for
      real financial time series and investigate their (in)efficient behavior by
      comparing three main stock indexes.

PMID- 28764402
TI  - Development of structural correlations and synchronization from adaptive rewiring
      in networks of Kuramoto oscillators.
AB  - Synchronization of non-identical oscillators coupled through complex networks is
      an important example of collective behavior, and it is interesting to ask how the
      structural organization of network interactions influences this process. Several
      studies have explored and uncovered optimal topologies for synchronization by
      making purposeful alterations to a network. On the other hand, the connectivity
      patterns of many natural systems are often not static, but are rather modulated
      over time according to their dynamics. However, this co-evolution and the extent
      to which the dynamics of the individual units can shape the organization of the
      network itself are less well understood. Here, we study initially randomly
      connected but locally adaptive networks of Kuramoto oscillators. In particular,
      the system employs a co-evolutionary rewiring strategy that depends only on the
      instantaneous, pairwise phase differences of neighboring oscillators, and that
      conserves the total number of edges, allowing the effects of local reorganization
      to be isolated. We find that a simple rule-which preserves connections between
      more out-of-phase oscillators while rewiring connections between more in-phase
      oscillators-can cause initially disordered networks to organize into more
      structured topologies that support enhanced synchronization dynamics. We examine
      how this process unfolds over time, finding a dependence on the intrinsic
      frequencies of the oscillators, the global coupling, and the network density, in
      terms of how the adaptive mechanism reorganizes the network and influences the
      dynamics. Importantly, for large enough coupling and after sufficient adaptation,
      the resulting networks exhibit interesting characteristics, including degree
      frequency and frequency-neighbor frequency correlations. These properties have
      previously been associated with optimal synchronization or explosive transitions
      in which the networks were constructed using global information. On the contrary,
      by considering a time-dependent interplay between structure and dynamics, this
      work offers a mechanism through which emergent phenomena and organization can
      arise in complex systems utilizing local rules.

PMID- 28764404
TI  - Levy noise-induced phenomena in CO oxidation on Ir(111) surfaces.
AB  - The influences of external Levy noise in CO oxidation on the Ir(111) surfaces are
      numerically examined. Depending on the control parameters, such as the
      temperature T  and the CO fraction Y  in the total reactant input gas flux, the
      reaction exhibits one or two stable stationary states in the absence of noise.
      Levy noise is introduced in the reaction by randomly varying the quality of the
      influx mixture. We then observe a large variety of different types of behaviors
      depending on the initial CO fraction Y, in particular, the phenomenon of noise
      induced shifts of the steady state in the monostable regime is regarded. We also
      show how the stationary probability density changes in terms of stochastic
      bifurcation when Levy noise is applied in the bistable regime. The results
      provide a strong evidence for noise-induced transitions. We concentrate on the
      effects of the stability index alpha, the skewness parameter beta,  and the noise
      intensity D  that emphasize the differences with Gaussian fluctuations.

PMID- 28764405
TI  - Local complexity predicts global synchronization of hierarchically networked
      oscillators.
AB  - We study the global synchronization of hierarchically-organized Stuart-Landau
      oscillators, where each subsystem consists of three oscillators with activity
      dependent couplings. We considered all possible coupling signs between the three
      oscillators, and found that they can generate different numbers of phase
      attractors depending on the network motif. Here, the subsystems are coupled
      through mean activities of total oscillators. Under weak inter-subsystem
      couplings, we demonstrate that the synchronization between subsystems is highly
      correlated with the number of attractors in uncoupled subsystems. Among the
      network motifs, perfect anti-symmetric ones are unique to generate both single
      and multiple attractors depending on the activities of oscillators. The flexible
      local complexity can make global synchronization controllable.

PMID- 28764406
TI  - Binary Darboux transformation for the coupled Sasa-Satsuma equations.
AB  - The binary Darboux transformation method is applied to the coupled Sasa-Satsuma
      equations, which can be used to describe the propagation dynamics of femtosecond
      vector solitons in the birefringent fibers with third-order dispersion, self
      steepening, and stimulated Raman scattering higher-order effects. An N-fold
      iterative formula of the resulting binary Darboux transformation is presented in
      terms of the quasideterminants. Via the simplest case of this formula, a few of
      illustrative explicit solutions to the coupled Sasa-Satsuma equations are
      generated from vanishing and non-vanishing backgrounds, which include the
      breathers, single- and double-hump bright vector solitons, and anti-dark vector
      solitons.

PMID- 28764407
TI  - Coexisting synchronous and asynchronous states in locally coupled array of
      oscillators by partial self-feedback control.
AB  - We report the emergence of coexisting synchronous and asynchronous subpopulations
      of oscillators in one dimensional arrays of identical oscillators by applying a
      self-feedback control. When a self-feedback is applied to a subpopulation of the
      array, similar to chimera states, it splits into two/more sub-subpopulations
      coexisting in coherent and incoherent states for a range of self-feedback
      strength. By tuning the coupling between the nearest neighbors and the amount of
      self-feedback in the perturbed subpopulation, the size of the coherent and the
      incoherent sub-subpopulations in the array can be controlled, although the exact
      size of them is unpredictable. We present numerical evidence using the Landau
      Stuart system and the Kuramoto-Sakaguchi phase model.

PMID- 28764408
TI  - Information theory and robotics meet to study predator-prey interactions.
AB  - Transfer entropy holds promise to advance our understanding of animal behavior,
      by affording the identification of causal relationships that underlie animal
      interactions. A critical step toward the reliable implementation of this powerful
      information-theoretic concept entails the design of experiments in which causal
      relationships could be systematically controlled. Here, we put forward a robotics
      based experimental approach to test the validity of transfer entropy in the study
      of predator-prey interactions. We investigate the behavioral response of
      zebrafish to a fear-evoking robotic stimulus, designed after the morpho
      physiology of the red tiger oscar and actuated along preprogrammed trajectories.
      From the time series of the positions of the zebrafish and the robotic stimulus,
      we demonstrate that transfer entropy correctly identifies the influence of the
      stimulus on the focal subject. Building on this evidence, we apply transfer
      entropy to study the interactions between zebrafish and a live red tiger oscar.
      The analysis of transfer entropy reveals a change in the direction of the
      information flow, suggesting a mutual influence between the predator and the
      prey, where the predator adapts its strategy as a function of the movement of the
      prey, which, in turn, adjusts its escape as a function of the predator motion.
      Through the integration of information theory and robotics, this study posits a
      new approach to study predator-prey interactions in freshwater fish.

PMID- 28764409
TI  - Significance of non-normality-induced patterns: Transient growth versus
      asymptotic stability.
AB  - Reaction-diffusion models following the original idea of Turing are widely
      applied to study the propensity of a system to develop a pattern. To this end, an
      asymptotic analysis is typically performed via the so-called dispersion relation
      that relates the spectral properties of a spatial operator (diffusion) to the
      temporal behaviour of the whole initial-boundary value reaction-diffusion
      problem. Here, we amend this approach by studying the transient growth due to non
      normality that can also lead to a pattern development in non-linear systems. We
      conclude by identification of the significance of this transient growth and by
      assessing the plausibility of the standard spectral approach. Particularly, the
      non-normality-induced patterns are possible but require fine parameter tuning.

PMID- 28764410
TI  - Public goods games on adaptive coevolutionary networks.
AB  - Productive societies feature high levels of cooperation and strong connections
      between individuals. Public Goods Games (PGGs) are frequently used to study the
      development of social connections and cooperative behavior in model societies. In
      such games, contributions to the public good are made only by cooperators, while
      all players, including defectors, reap public goods benefits, which are shares of
      the contributions amplified by a synergy factor. Classic results of game theory
      show that mutual defection, as opposed to cooperation, is the Nash Equilibrium of
      PGGs in well-mixed populations, where each player interacts with all others. In
      this paper, we explore the coevolutionary dynamics of a low information public
      goods game on a complex network in which players adapt to their environment in
      order to increase individual payoffs relative to past payoffs parameterized by
      greediness. Players adapt by changing their strategies, either to cooperate or to
      defect, and by altering their social connections. We find that even if players do
      not know other players' strategies and connectivity, cooperation can arise and
      persist despite large short-term fluctuations.

PMID- 28764411
TI  - Adaptive filtering for hidden node detection and tracking in networks.
AB  - The identification of network connectivity from noisy time series is of great
      interest in the study of network dynamics. This connectivity estimation problem
      becomes more complicated when we consider the possibility of hidden nodes within
      the network. These hidden nodes act as unknown drivers on our network and their
      presence can lead to the identification of false connections, resulting in
      incorrect network inference. Detecting the parts of the network they are acting
      on is thus critical. Here, we propose a novel method for hidden node detection
      based on an adaptive filtering framework with specific application to neuronal
      networks. We consider the hidden node as a problem of missing variables when
      model fitting and show that the estimated system noise covariance provided by the
      adaptive filter can be used to localize the influence of the hidden nodes and
      distinguish the effects of different hidden nodes. Additionally, we show that the
      sequential nature of our algorithm allows for tracking changes in the hidden node
      influence over time.

PMID- 28764412
TI  - The nonlinear Schrodinger equation with generalized nonlinearities and PT
      symmetric potentials: Stable solitons, interactions, and excitations.
AB  - We investigate the nonlinear Schrodinger (NLS) equation with generalized
      nonlinearities and complex non-Hermitian potentials and present the novel parity
      time-( PT-) symmetric potentials for the NLS equation with power-law
      nonlinearities supporting some bright solitons. For distinct types of PT
      symmetric potentials including Scarf-II, Hermite-Gaussian, and asymptotically
      periodic potentials, we, respectively, explore the phase transitions for the
      linear Hamiltonian operators. Moreover, we analytically find stable bright
      solitons in the generalized NLS equations with several types of PT-symmetric
      potentials, and their stability is corroborated by the linear stability spectrum
      and direct wave-propagation simulations. Interactions of two solitons are also
      explored. More interestingly, we find that the nonlinearity can excite the
      unstable linear modes (i.e., possessing broken linear PT-symmetric phase) to
      stable nonlinear modes. The results may excite potential applications in
      nonlinear optics, Bose-Einstein condensates, and relevant fields.

PMID- 28764413
TI  - Fisher information and Renyi entropies in dynamical systems.
AB  - The link between the Fisher information and Renyi entropies is explored. The
      relationship is based on a thermodynamical formalism based on Fisher information
      with a parameter, beta, which is interpreted as the inverse temperature. The
      Fisher heat capacity is defined and found to be sensitive to changes of higher
      order than the analogous quantity in the conventional formulation.

PMID- 28764414
TI  - Effect of the static compressive load on vibration propagation in multistory
      buildings and resulting heavyweight floor impact sounds.
AB  - Experiments were performed to identify the mechanism of heavyweight floor impact
      sound transmission through floors in a high-rise apartment building. Vibration
      and sound levels on each floor of the multistory building were measured. The
      vibration generated at a given floor was transferred to multiple adjacent floors
      with decreasing amplitudes proportional to the distance from the excited floor.
      This vibration transfer introduced significant sound transmissions. The
      structural static load varied depending on the floor location due to differences
      in the weight of the structure above the floor, especially for wall construction
      buildings. The static load at the wall of the bottom floor was the largest among
      the different floors. The influence of this static load on the impact sound
      generation was investigated through tests in the actual building and the scale
      model, respectively. The results were numerically analyzed using the spectral
      element method. With the increasing static load, the resonance frequencies of the
      floor increased due to the change in the vibration modes of the structure. The
      modulated sound generation from the floor vibrations transmitted to multiple
      layers with larger magnitudes due to this static load.

PMID- 28764415
TI  - Sparse dictionary for synthetic transmit aperture medical ultrasound imaging.
AB  - It is possible to recover a signal below the Nyquist sampling limit using a
      compressive sensing technique in ultrasound imaging. However, the reconstruction
      enabled by common sparse transform approaches does not achieve satisfactory
      results. Considering the ultrasound echo signal's features of attenuation,
      repetition, and superposition, a sparse dictionary with the emission pulse signal
      is proposed. Sparse coefficients in the proposed dictionary have high sparsity.
      Images reconstructed with this dictionary were compared with those obtained with
      the three other common transforms, namely, discrete Fourier transform, discrete
      cosine transform, and discrete wavelet transform. The performance of the proposed
      dictionary was analyzed via a simulation and experimental data. The mean absolute
      error (MAE) was used to quantify the quality of the reconstructions. Experimental
      results indicate that the MAE associated with the proposed dictionary was always
      the smallest, the reconstruction time required was the shortest, and the lateral
      resolution and contrast of the reconstructed images were also the closest to the
      original images. The proposed sparse dictionary performed better than the other
      three sparse transforms. With the same sampling rate, the proposed dictionary
      achieved excellent reconstruction quality.

PMID- 28764416
TI  - Sound radiation from impact-driven raked piles.
AB  - Sound emissions from impact pile driving of raked piles present a significant
      azimuthal dependence in the radiated sound field due to the non-axisymmetric
      orientation of the pile. In this work the sound radiation from raked piles is
      modeled using a finite element method (FEM) model of the pile and near-field
      region. The near-field model of the sound field is then used as input into a
      normal mode model to predict the sound radiation in the far-field. The azimuthal
      dependence of the radiated sound field is shown to be accurately predicted using
      an equivalent axisymmetric FEM model of the pile configuration, thus negating the
      need to construct a fully three-dimensional model (3D) of the raked pile. This is
      achieved by matching the radiated field from the equivalent axisymmetric pile
      model to a vertical array of phased point sources, and then horizontally
      offsetting the source locations to match the incline of the raked pile. The
      resulting sound field closely matches the numerical predictions from a fully 3D
      FEM model of the raked pile. The results of numerical modeling are compared to
      corresponding acoustic measurements taken on the North West shelf of Western
      Australia.

PMID- 28764417
TI  - Matched shadow processing.
AB  - Traditional matched field processing is based on the comparison of the complex
      amplitudes of the measured and calculated wave fields at the aperture of the
      receiving antenna. This paper considers an alternative approach based on
      comparing the intensity distributions of these fields in the "depth - arrival
      angle" plane. To construct these intensities, the formalism of coherent states
      borrowed from quantum mechanics is used. The main advantage of the approach under
      consideration is its low sensitivity to the inevitable inaccuracy of an
      environmental model used in calculation.

PMID- 28764418
TI  - Localization and separation of acoustic sources by using a 2.5-dimensional
      circular microphone array.
AB  - Circular microphone arrays (CMAs) are sufficient in many immersive audio
      applications because azimuthal angles of sources are considered more important
      than the elevation angles in those occasions. However, the fact that CMAs do not
      resolve the elevation angle well can be a limitation for some applications which
      involves three-dimensional sound images. This paper proposes a 2.5-dimensional
      (2.5-D) CMA comprised of a CMA and a vertical logarithmic-spacing linear array
      (LLA) on the top. In the localization stage, two delay-and-sum beamformers are
      applied to the CMA and the LLA, respectively. The direction of arrival (DOA) is
      estimated from the product of two array output signals. In the separation stage,
      Tikhonov regularization and convex optimization are employed to extract the
      source amplitudes on the basis of the estimated DOA. The extracted signals from
      two arrays are further processed by the normalized least-mean-square algorithm
      with the internal iteration to yield the source signal with improved quality. To
      validate the 2.5-D CMA experimentally, a three-dimensionally printed circular
      array comprised of a 24-element CMA and an eight-element LLA is constructed.
      Objective perceptual evaluation of speech quality test and a subjective listening
      test are also undertaken.

PMID- 28764419
TI  - Linguistic masking release in young and older adults with age-appropriate hearing
      status.
AB  - Past studies of speech-on-speech masking in young adults (YA) indicate that the
      intelligibility of masked speech can improve if the target and masker speech are
      in different languages. Current work investigated whether a linguistic masking
      release is obtained in older adults (OA) with age-typical hearing abilities.
      Participants listened to English sentences in the presence of two-talker Spanish
      or English maskers. A similar masking release with Spanish-language maskers was
      obtained for OA and YA listeners, despite greater accuracy by YA listeners. In
      speech-on-speech masking, older listeners can thus improve speech intelligibility
      by utilizing nonenergetic linguistic differences between the target and masker
      speech.

PMID- 28764420
TI  - Fronting of Southern British English high-back vowels in articulation and
      acoustics.
AB  - The fronting of the two high-back vowels /u?/ and /upsilon/ in Southern British
      English is very well documented, but mainly in the acoustic domain. This paper
      presents articulatory (ultrasound) data, comparing the relative tongue position
      of these vowels in fronting and non-fronting consonantal contexts, i.e.,
      preceding a coronal consonant (food, foot) and preceding a coda /l/ (fool, full).
      Particular attention is paid to the comparison between articulatory results and
      corresponding acoustic measurements of F2 in both vowels. Results show that the
      average differences between food and foot and their dynamic profiles are similar
      in articulation and acoustics. In /u?l/ sequences (fool), tongue position is more
      advanced than could be inferred from its low F2. In addition, even though the
      tongue position in fool and full is clearly distinct, there is no comparable
      corresponding difference in F2. This suggests that the common articulatory
      metaphor that characterises F2 increase as fronting must be used cautiously. In
      the case of English high-back vowel fronting, special attention must be paid to
      the flanking consonants when estimating vowel distances. This paper also provides
      specific recommendations for recording and analysing ultrasound data in research
      on vowel variation and change.

PMID- 28764421
TI  - A variational data assimilation system for the range dependent acoustic model
      using the representer method: Theoretical derivations.
AB  - This study presents the theoretical framework for variational data assimilation
      of acoustic pressure observations into an acoustic propagation model, namely, the
      range dependent acoustic model (RAM). RAM uses the split-step Pade algorithm to
      solve the parabolic equation. The assimilation consists of minimizing a weighted
      least squares cost function that includes discrepancies between the model
      solution and the observations. The minimization process, which uses the principle
      of variations, requires the derivation of the tangent linear and adjoint models
      of the RAM. The mathematical derivations are presented here, and, for the sake of
      brevity, a companion study presents the numerical implementation and results from
      the assimilation simulated acoustic pressure observations.

PMID- 28764422
TI  - A sliding two-alternative forced-choice paradigm for pitch discrimination.
AB  - Studies that measure frequency discrimination often use 2, 3, or 4 tones per
      trial. This paper shows an investigation of a two-alternative forced choice
      (2AFC) task in which each tone of a series is judged relative to the previous
      tone ("sliding 2AFC"). Potential advantages are a greater yield (number of
      responses per unit time), and a more uniform history of stimulation for the study
      of context effects, or to relate time-varying performance to cortical activity.
      The new task was evaluated relative to a classic 2-tone-per-trial 2AFC task with
      similar stimulus parameters. For each task, conditions with different stimulus
      parameters were compared. The main results were as follows: (1) thresholds did
      not differ significantly between tasks when similar parameters were used. (2)
      Thresholds did differ between conditions for the new task, showing a deleterious
      effect of inserting relatively large steps in the frequency sequence. (3)
      Thresholds also differed between conditions for the classic task, showing an
      advantage for a fixed frequency standard. There was no indication that results
      were more variable with either task, and no reason was found not to use the new
      sliding 2AFC task in lieu of the classic 2-tone-per-trial 2AFC task.

PMID- 28764423
TI  - Introduction to the Special Issue on Advancing Methods for Analyzing Dialect
      Variation.
AB  - Documenting and analyzing dialect variation is traditionally the domain of
      dialectology and sociolinguistics. However, modern approaches to acoustic
      analysis of dialect variation have their roots in Peterson and Barney's [(1952).
      J. Acoust. Soc. Am. 24, 175-184] foundational work on the acoustic analysis of
      vowels that was published in the Journal of the Acoustical Society of America
      (JASA) over 6 decades ago. Although Peterson and Barney (1952) were not primarily
      concerned with dialect variation, their methods laid the groundwork for the
      acoustic methods that are still used by scholars today to analyze vowel variation
      within and across languages. In more recent decades, a number of methodological
      advances in the study of vowel variation have been published in JASA, including
      work on acoustic vowel overlap and vowel normalization. The goal of this special
      issue was to honor that tradition by bringing together a set of papers describing
      the application of emerging acoustic, articulatory, and computational methods to
      the analysis of dialect variation in vowels and beyond.

PMID- 28764424
TI  - Blind localization and segregation of two sources including a binaural head
      movement model.
AB  - This study investigates how virtual head rotations can improve a binaural model's
      ability to segregate speech signals. The model takes two mixed speech sources
      spatialized to unique azimuth positions and localizes them. The model virtually
      rotates its head to orient itself for the maximum signal-to-noise ratio for
      extracting the target. An equalization-cancellation approach is used to generate
      a binary mask for the target based on localization cues. The mask is then
      overlaid onto the mixed signal's spectrogram to extract the target from the
      mixture. Improvement in signal-to-noise ratios from head rotation approaches over
      30 dB.

PMID- 28764425
TI  - Modulation of high frequency noise by engine tones of small boats.
AB  - The effect of modulation of high frequency ship noise by propeller rotation
      frequencies is well known. This modulation is observed with the Detection of
      Envelope Modulation on Noise (DEMON) algorithm. Analysis of the DEMON spectrum
      allows the revolutions per minute and number of blades of the propeller to be
      determined. This work shows that the high frequency noise of a small boat can
      also be modulated by engine frequencies. Prior studies have not reported high
      frequency noise amplitude modulated at engine frequencies. This modulation is
      likely produced by bubbles from the engine exhaust system.

PMID- 28764426
TI  - Three-dimensional reconstruction of nonplanar ultrasound fields using Radon
      transform and the schlieren imaging method.
AB  - This paper introduces a numerical method of reconstructing three-dimensional (3D)
      ultrasound fields from their two-dimensional back-projections to understand the
      intensity distribution of nonplanar waves. The horizontal planes for line-focused
      ultrasound fields were roughly elliptical, whereas those for point-focused
      ultrasound fields were nearly circular. Experimental and simulated results
      indicated that the ultrasound intensity at the central axis can be calibrated
      from the light intensity by 3D reconstruction of the ultrasound field. The
      difference between the measured ultrasound intensity for nonplanar waves in
      schlieren imaging and the simulation results were discussed. From this work, the
      3D ultrasound field becomes possible to be reconstructed.

PMID- 28764427
TI  - Quantitative identification of dialect-specific articulatory settings.
AB  - The purpose of this study was to quantitatively contrast the articulatory
      settings of two Dutch dialects. Tongue movement data during speech were collected
      on site at two high schools (34 speakers) in the Netherlands using a portable
      electromagnetic articulography device. Comparing the tongue positions during
      pauses in speech between the two groups revealed a clear difference in the
      articulatory settings, with significantly more frontal tongue positions for the
      speakers from Ubbergen in the Southeast of the Netherlands compared to those from
      Ter Apel in the North of the Netherlands. These results provide quantitative
      evidence for differences in articulatory settings at the dialect level.

PMID- 28764428
TI  - Diffuse ultrasonic backscatter using a multi-Gaussian beam model.
AB  - Diffuse ultrasonic backscatter is widely used to evaluate microstructural
      parameters of heterogeneous materials. Recent singly scattered response (SSR)
      models utilize a single-Gaussian beam (SGB) assumption which is expected to have
      limitations. Following a similar formalism, a model is presented using a multi
      Gaussian beam (MGB) assumption to characterize the transducer beam for
      longitudinal-to-longitudinal scattering at normal incidence through an interface
      with arbitrary curvature. First, the Wigner transform of the transducer field is
      defined using conjugate double-layer MGB expressions. The theoretical analysis
      shows that ten groups of Gaussian beams are sufficient for convergence. Compared
      with the SGB-SSR curve, the shape of MGB-SSR curve is positive skewed.
      Differences between the MGB-SSR model and the SGB-SSR model are quantified and
      shown to be complex functions of frequency, sample curvature, transducer
      parameters, and focal depth in the material. Finally, both models are used to fit
      experimental spatial variance data from a 304 stainless steel pipe with planar,
      convex, and concave surfaces. The results show that the MGB-SSR has some
      characteristics suggesting a better fit to the experiments. However, both models
      result in grain size estimates within the uncertainty of the optical microscopy
      suggesting that the SGB is sufficient for normal incidence pulse-echo
      measurements.

PMID- 28764429
TI  - Non-negative intensity and back-calculated non-negative intensity for analysis of
      directional structure-borne sound.
AB  - Non-negative intensity (NNI) is an approach to identify the surface areas of a
      structure that contribute to sound power. NNI is evaluated in terms of the
      acoustic impedance matrix obtained directly at the structural surface and as such
      can only identify surface contributions to sound power at a far-field receiver
      surface that fully circumscribes the structure. In contrast, back-calculated NNI
      is evaluated in terms of the acoustic impedance matrix obtained at a far-field
      receiver surface, and hence can identify surface contributions to sound power at
      a far-field receiver surface that does not fully circumscribe the structure. In
      this work, NNI and acoustic intensity obtained numerically using the boundary
      element method and experimentally from near-field acoustic holography
      measurements are compared for different modes. Back-calculated NNI evaluated for
      full and partial receiver surfaces is also compared with acoustic intensity for
      the different modes. Results for back-calculated NNI show that different regions
      on the plate surface contribute sound to different receiver locations.

PMID- 28764430
TI  - Matched guise effects can be robust to speech style.
AB  - When investigating how listeners evaluate the social meaning of variability in
      speech, researchers using the Matched Guise Technique (MGT) must decide whether
      to use read speech or conversational speech stimuli. An MGT experiment comparing
      social evaluation of /in/ ~ /in/ variation in read and conversational speech
      styles found no evidence that the social evaluation of this variation differed
      across frame utterance styles. This suggests that use of read speech stimuli can
      be an appropriate methodological choice in MGT research.

PMID- 28764431
TI  - Bat Bioacoustics.

PMID- 28764432
TI  - Modeling consonant-context effects in a large database of spontaneous speech
      recordings.
AB  - Given recent interest in the analysis of naturally produced spontaneous speech, a
      large database of speech samples from the Canadian Maritimes was collected,
      processed, and analyzed with the primary aim of examining vowel-inherent spectral
      change in formant trajectories. Although it takes few resources to collect a
      large sample of audio recordings, the analysis of spontaneous speech introduces a
      number of difficulties compared to that of laboratory citation speech:
      Surrounding consonants may have a large influence on vowel formant frequencies
      and the distribution of consonant contexts is highly unbalanced. To overcome
      these problems, a statistical procedure inspired by that of Broad and Clermont
      [(2014). J. Phon. 47, 47-80] was developed to estimate the magnitude of both
      onset and coda effects on vowel formant frequencies. Estimates of vowel target
      formant frequencies and the parameters associated with consonant-context effects
      were allowed to vary freely across the duration of the vocalic portion of a
      syllable which facilitated the examination of vowel-inherent spectral change.
      Thirty-five hours of recorded speech samples from 223 speakers were automatically
      segmented and formant-frequency values were measured for all stressed vowels in
      the database. Consonant effects were accounted for to produce context-normalized
      vowel formant frequencies that varied across time.

PMID- 28764433
TI  - Tracking the phonological status of /l/ in Newfoundland English: Experiments in
      articulation and acoustics.
AB  - This paper investigates patterning of /l/ in Newfoundland English. Using acoustic
      and ultrasound methods, the reported displacement of the traditional Irish
      pattern of word-final light /l/ is assessed. Acoustic results show darker /l/'s
      in word-final position in both phrases and compounds. Although the standard
      allophonic pattern is widespread in Newfoundland English, dialectal variation
      arising from early settlement patterns continues to influence speech patterns
      with less distinction between initial and final /l/ in Irish-settled areas. Men
      show relatively less distinction between initial and final /l/, consistent with
      sociolinguistic patterns in which men retain local variants. Last, light /l/ in
      final position may be resurfacing among younger speakers. Ultrasound imaging also
      shows variable rates of distinction between word-final and initial /l/, but
      without significant main effects of region or gender. Articulatory analysis
      reveals a small effect of age, with older speakers being less likely to have
      significant differences in articulation across positions. An interaction between
      region and gender shows males from an Irish-settled community are less likely to
      employ distinct lingual shapes across positions. While some articulatory findings
      complement the acoustic results, it is suggested that differences between these
      domains result from lateralization or other aspects of articulation not captured
      in ultrasound imaging.

PMID- 28764434
TI  - Underwater sound radiation from an elastically coated infinite plate with
      periodic inhomogeneities of finite width.
AB  - The underwater sound radiation from a line-force-driven coated infinite plate
      with periodically attached distributed inhomogeneities is investigated. A typical
      example of a distributed inhomogeneity is a signal conditioning plate (SCP),
      which can be inserted between the coating and a hydrophone to increase the
      strength of the incoming signal. Using the wavenumber transform approach, the
      surface normal velocity and radiated sound power of the plate are determined by
      solving the indexed equations of the wavenumber components. This study
      demonstrates that the elastic coating between the base plate and periodic
      inhomogeneities may reduce the effect of band-passes and band-gaps on the
      radiated sound power caused by the inhomogeneities. This is explained in detail
      by the insulation effect of the coating as a decoupler. The effect of the SCP's
      width and spatial period on the radiated sound is also examined. Finally,
      recommendations are given for the application of SCPs for underwater sensing
      purposes.

PMID- 28764435
TI  - Design and demonstration of an acoustic right-angle bend.
AB  - In this paper, a broadband acoustic right-angle bend device in air is designed,
      fabricated and experimentally characterized. Perforated panels with various hole
      sizes are used to construct the bend structure. Both the simulated and
      experimental results verify that the acoustic beam can be rotated effectively
      through the acoustic bend in a wide frequency range. This model may have
      potential applications in some areas such as sound absorption and acoustic
      detection in elbow pipes.

PMID- 28764436
TI  - Extraction of scattering echo time by surf noise background subtracted
      autocorrelation.
AB  - Extracting echo time is an important step in scatterer detection by ambient
      noise, while in general the scattered signal is weak and submerged in the
      background. An experiment of a Polyvinyl chloride pipe in a coastline surf noise
      environment is designed to extract the pipe's echo time by noise autocorrelation.
      As expected, the scattered wave of the pipe is submerged in an autocorrelation
      signal. A method called background subtracted autocorrelation is proposed in this
      paper, which can retrieve scattered echo time from autocorrelation signal
      effectively. And the biggest relative error of extracted echo time is less than
      2% in the experiment.

PMID- 28764437
TI  - Generation of broadband surface acoustic waves using a dual temporal-spatial
      chirp method.
AB  - Wideband surface acoustic wave (SAW) generation with a spatial chirp-based
      interdigital transducer was optimized for non-destructive characterization and
      testing of coatings and thin layers. The use of impulse temporal excitation
      (Dirac-type negative pulse) leads to a wide band emitter excitation but with
      significantly limited SAW output amplitudes due to the piezoelectric crystal
      breakdown voltage. This limitation can be circumvented by applying a temporal
      chirp excitation corresponding in terms of frequency band and duration to the
      spatial chirp transducer configuration. This dual temporal-spatial chirp method
      was studied in the 20 to 125 MHz frequency range and allowed to obtain higher SAW
      displacement amplitudes with an excitation voltage lower than that of the impulse
      excitation.

PMID- 28764438
TI  - Sound source localization identification accuracy: Envelope dependencies.
AB  - Sound source localization accuracy as measured in an identification procedure in
      a front azimuth sound field was studied for click trains, modulated noises, and a
      modulated tonal carrier. Sound source localization accuracy was determined as a
      function of the number of clicks in a 64 Hz click train and click rate for a 500
      ms duration click train. The clicks were either broadband or high-pass filtered.
      Sound source localization accuracy was also measured for a single broadband
      filtered click and compared to a similar broadband filtered, short-duration
      noise. Sound source localization accuracy was determined as a function of
      sinusoidal amplitude modulation and the "transposed" process of modulation of
      filtered noises and a 4 kHz tone. Different rates (16 to 512 Hz) of modulation
      (including unmodulated conditions) were used. Providing modulation for filtered
      click stimuli, filtered noises, and the 4 kHz tone had, at most, a very small
      effect on sound source localization accuracy. These data suggest that amplitude
      modulation, while providing information about interaural time differences in
      headphone studies, does not have much influence on sound source localization
      accuracy in a sound field.

PMID- 28764439
TI  - Comparing malleability of phonetic category between [i] and [u].
AB  - This study reports differential category retuning effect between [i] and [u]. Two
      groups of American listeners were exposed to ambiguous vowels ([i/u]) within
      words that index a phoneme /i/ (e.g., athl[i/u]t) (i-group) or /u/ (e.g.,
      aftern[i/u]n) (u-group). Before and after the exposure these listeners
      categorized sounds from a [bip]-[bup] continuum. The i-group significantly
      increased /bip/ responses after exposure, but the u-group did not change their
      responses significantly. These results suggest that the way mental representation
      handles phonetic variation may influence malleability of each category,
      highlighting the complex relationship among distribution of sounds, their mental
      representation, and speech perception.

PMID- 28764440
TI  - The effect of transducer directivity on time reversal focusing.
AB  - This letter explores the effect of the directivity of a source on time reversal
      acoustic focusing of energy. A single loudspeaker produces an airborne focus of
      sound in a reverberation chamber and in a classroom. Individual foci are created
      at microphone positions that surround the loudspeaker. The primary axis of the
      loudspeaker is then rotated and experiments are repeated to average out the room
      response. Focal amplitude, temporal quality of the foci, and spatial focusing
      quality are compared to determine the optimal angle to aim a directional source
      axis relative to the desired focal position.

PMID- 28764441
TI  - Effects of reverberation, background talker number, and compression release time
      on signal-to-noise ratio.
AB  - Wide dynamic range compression (WDRC) processing in hearing aids alters the
      signal-to-noise ratio (SNR) of a speech-in-noise signal. This effect depends on
      the modulations of the speech and noise, input SNR, and WDRC speed. The purpose
      of the present experiment was to examine the change in output SNR caused by the
      interaction between modulation characteristics and WDRC speed. Two modulation
      manipulations were examined: (1) reverberation and (2) variation in background
      talker number. Results indicated that fast-acting WDRC altered SNR more than slow
      acting WDRC; however, reverberation reduced this difference. Additionally, less
      modulated maskers led to poorer output SNRs than modulated maskers.

PMID- 28764442
TI  - Inverse identification of the acoustic porous parameters of double-layered
      poroelastic structures by acoustic rigidity approximation.
AB  - A method to characterize the porous parameters (i.e., tortuosity, flow
      resistivity, viscous, and thermal lengths) of double-layered poroelastic
      structures is proposed and validated. The porosity, elastic coefficients
      (estimated), frame density, and thickness of each layer are assumed to be known.
      The way is to first identify the effective density and bulk modulus of each layer
      by a system of equations established based on the measured surface impedance of
      the structures backed by various air cavities, and then extract the porous
      parameters from the above identified parameters through the least square method
      at frequencies where the effect of vibration of frame is trivial. Because of the
      insensitivity to the surface impedance and the negligibility of the thermal loss
      compared to the viscous dissipation, the two acoustical bulk moduli are assumed
      to be identical. Two double-layered structures are constructed, which parameters
      are identified by the proposed method, and further verified by experiments.
      Simulations show that for double-layered structures constructed by materials with
      large frame density (viscous length) or small flow resistivity, the identified
      precision would be better. In addition, because of the identical assumption, the
      ratio of two thermal lengths should not exceed two or be less than one half.

PMID- 28764443
TI  - Wide-angle asymmetric acoustic absorber based on one-dimensional lossy Bragg
      stacks.
AB  - Based on one-dimensional lossy Bragg stacks, an asymmetric absorber is realized
      for low-frequency sound waves, that is, perfect absorption can be obtained when
      sound waves are normally incident from one side while a small absorption can be
      obtained from the opposite side. Moreover, the asymmetric absorption persists for
      a wide incident angle of sound waves in the range from 0 degrees  to 42 degrees 
      with the absorptive coefficient larger than 90% from one side while less than 20%
      from the other side. By changing the thickness of the top sublayer, a series of
      interesting absorption phenomena such as Fano-resonance type absorption are
      further investigated.

PMID- 28764444
TI  - Development of frequency discrimination at 250 Hz is similar for tone and /ba/
      stimuli.
AB  - Frequency discrimination was measured in 5- to 11-year-olds and adults with
      normal hearing. The standard stimulus was either a 250-Hz tone or the syllable
      /ba/ with a fundamental frequency (F0) of 250 Hz. Target stimuli were higher in
      frequency than the standard, and the threshold for frequency discrimination was
      determined adaptively for each of the two stimulus types separately. For both the
      tone and /ba/ stimuli, thresholds improved approximately linearly with the log of
      child age, reaching adult levels by 11.5 years of age. There was no evidence of
      an effect of stimulus type.

PMID- 28764445
TI  - Effect of F0 contours on top-down repair of interrupted speech.
AB  - Top-down repair of interrupted speech can be influenced by bottom-up acoustic
      cues such as voice pitch (F0). This study aims to investigate the role of the
      dynamic information of pitch, i.e., F0 contours, in top-down repair of speech.
      Intelligibility of sentences interrupted with silence or noise was measured in
      five F0 contour conditions (inverted, flat, original, exaggerated with a factor
      of 1.5 and 1.75). The main hypothesis was that manipulating F0 contours would
      impair linking successive segments of interrupted speech and thus negatively
      affect top-down repair. Intelligibility of interrupted speech was impaired only
      by misleading dynamic information (inverted F0 contours). The top-down repair of
      interrupted speech was not affected by any F0 contours manipulation.

PMID- 28764446
TI  - Sound-Power Flow-A Practitioner's Handbook for Sound Intensity.

PMID- 28764447
TI  - A comparison of acoustic and articulatory methods for analyzing vowel differences
      across dialects: Data from American and Australian English.
AB  - In studies of dialect variation, the articulatory nature of vowels is sometimes
      inferred from formant values using the following heuristic: F1 is inversely
      correlated with tongue height and F2 is inversely correlated with tongue
      backness. This study compared vowel formants and corresponding lingual
      articulation in two dialects of English, standard North American English, and
      Australian English. Five speakers of North American English and four speakers of
      Australian English were recorded producing multiple repetitions of ten
      monophthongs embedded in the /sVd/ context. Simultaneous articulatory data were
      collected using electromagnetic articulography. Results show that there are
      significant correlations between tongue position and formants in the direction
      predicted by the heuristic but also that the relations implied by the heuristic
      break down under specific conditions. Articulatory vowel spaces, based on tongue
      dorsum position, and acoustic vowel spaces, based on formants, show systematic
      misalignment due in part to the influence of other articulatory factors,
      including lip rounding and tongue curvature on formant values. Incorporating
      these dimensions into dialect comparison yields a richer description and a more
      robust understanding of how vowel formant patterns are reproduced within and
      across dialects.

PMID- 28764449
TI  - Intensimetric detection of distortion product otoacoustic emissions with ear
      canal calibration.
AB  - Distortion product otoacoustic emissions (DPOAEs) have been accurately measured
      with an intensimetric technique, involving simultaneous measure of pressure and
      velocity in the ear canal, which allows one to correctly calibrate both the input
      stimuli and the otoacoustic emission (OAE) level. Suitable combinations of
      standard intensimetric quantities, active intensity and power density [Stanzial,
      Shiffrer, and Sacchi, J. Acoust. Soc. Am. 131, 269-280 (2012)], are used to
      equalize the stimuli transmitted to the middle ear, and to estimate the DPOAE
      level emitted by the eardrum. The DPOAE intensimetric spectra are consistent with
      those recorded with a high-quality conventional otoacoustic probe with state-of
      the-art calibration of both stimulus and OAE response [Charaziak and Shera, J.
      Acoust. Soc. Am. 141, 515-525 (2017)], demonstrating the applicability of the
      intensimetric method to OAE measurements.

PMID- 28764448
TI  - Call divergence in three sympatric Rattus species.
AB  - To reduce errors in species recognition and the probability of interbreeding that
      lowers fitness, individuals within sympatric zones shift the signals to
      differentiate from those of other species. In the present study, the differences
      of the acoustic features of ultrasounds (courtship calls during heterosexual
      encounters) and audible calls (distress calls during tail-clamp stress) are
      compared among three sympatric Rattus species (Rattus andamanensis, R.
      norvegicus, and R. losea). Results showed that the three species have
      significantly different call parameters, including call duration, peak frequency,
      bandwidth, pitch, goodness of pitch, frequency modulation, and Wiener entropy.
      This study provides quantitative evidence for character displacement in the
      acoustic signals of closely related sympatric Rattus species. Results indicate
      that the divergence of acoustic signal has arrived at the quite meticulous degree
      of evolution. Therefore, the acoustic signal trait is likely involved in the
      evolution of species diversity in rodents.

PMID- 28764450
TI  - The articulatory dynamics of pre-velar and pre-nasal /ae/-raising in English: An
      ultrasound study.
AB  - Most dialects of North American English exhibit /ae/-raising in some phonological
      contexts. Both the conditioning environments and the temporal dynamics of the
      raising vary from region to region. To explore the articulatory basis of /ae/
      raising across North American English dialects, acoustic and articulatory data
      were collected from a regionally diverse group of 24 English speakers from the
      United States, Canada, and the United Kingdom. A method for examining the
      temporal dynamics of speech directly from ultrasound video using EigenTongues
      decomposition [Hueber, Aversano, Chollet, Denby, Dreyfus, Oussar, Roussel, and
      Stone (2007). in IEEE International Conference on Acoustics, Speech and Signal
      Processing (Cascadilla, Honolulu, HI)] was applied to extract principal
      components of filtered images and linear regression to relate articulatory
      variation to its acoustic consequences. This technique was used to investigate
      the tongue movements involved in /ae/ production, in order to compare the tongue
      gestures involved in the various /ae/-raising patterns, and to relate them to
      their apparent phonetic motivations (nasalization, voicing, and tongue position).

PMID- 28764451
TI  - Iterative range estimation in a sloping-bottom shallow-water waveguide using the
      generalized array invariant.
AB  - The array invariant theory was generalized by incorporating the waveguide
      invariant beta, referred to as the generalized array invariant. In this paper,
      the generalized array invariant is extended to mildly range-dependent
      environments with a sloping bottom where the waveguide invariant is variable in
      range. Assuming knowledge of the bottom slope, the array invariant can be applied
      iteratively to estimate the source range starting with beta = 1 (i.e., range
      independent), which converges toward the correct source range by updating beta at
      the previously estimated range. The iterative array invariant approach is
      demonstrated using a short-aperture vertical array (2.8-m) in a sloping-bottom
      shallow-water waveguide from the Random Array of Drifting Acoustic Receivers 2007
      experiment, where a high-frequency source (2-3.5 kHz) close to the surface (6-m)
      was towed between 0.5 and 5 km in range with the water depth varying from 80 to
      50 m.

PMID- 28764452
TI  - Modeling speech localization, talker identification, and word recognition in a
      multi-talker setting.
AB  - This study introduces a model for solving three different auditory tasks in a
      multi-talker setting: target localization, target identification, and word
      recognition. The model was used to simulate psychoacoustic data from a call-sign
      based listening test involving multiple spatially separated talkers [Brungart and
      Simpson (2007). Percept. Psychophys. 69(1), 79-91]. The main characteristics of
      the model are (i) the extraction of salient auditory features ("glimpses") from
      the multi-talker signal and (ii) the use of a classification method that finds
      the best target hypothesis by comparing feature templates from clean target
      signals to the glimpses derived from the multi-talker mixture. The four features
      used were periodicity, periodic energy, and periodicity-based interaural time and
      level differences. The model results widely exceeded probability of chance for
      all subtasks and conditions, and generally coincided strongly with the subject
      data. This indicates that, despite their sparsity, glimpses provide sufficient
      information about a complex auditory scene. This also suggests that complex
      source superposition models may not be needed for auditory scene analysis.
      Instead, simple models of clean speech may be sufficient to decode even complex
      multi-talker scenes.

PMID- 28764453
TI  - Concrete wave dispersion interpretation through Mindlin's strain gradient elastic
      theory.
AB  - Classical elastic wave features like pulse velocity and attenuation have been
      used for decades for concrete condition characterization. Relatively recently the
      effect of frequency has been studied showing no doubt over the dispersive
      behavior of the material. Despite the experimental evidence, there is no unified
      theory to model the material and explain this phase velocity change at
      frequencies below 200 kHz. Herein, the Mindlin's strain gradient elastic theory
      including the additional micro-stiffness and micro-inertia parameters is
      considered as an alternative of multiple scattering theory. Experimental results
      are produced from material with dictated microstructure using a specific diameter
      of glass beads in cement paste. Results show that Mindlin's theory provides
      conclusions on the microstructure of the material and is suitable for describing
      the observed dispersion in different length scales (from millimeters in the case
      of mortar to several centimeters in the case of concrete).

PMID- 28764455
TI  - Experimental estimation of in vacuo structural admittance using random sources in
      a non-anechoic room.
AB  - Identification of unexploded ordinance buried in the sediment in the littoral
      waters throughout the world is a problem of great concern. When illuminated by
      low-frequency sonar some of these targets exhibit an elastic response that can be
      used to identify them. This elastic behavior is embodied and identified by a
      quantity called the in vacuo structural admittance matrix Ys, a relationship
      between the sonar-induced forces and resulting vibration on its surface. When it
      is known it can be combined with surface impedances to predict the three
      dimensional bistatic scattering in any fluid-like media and for any burial state
      (depth and orientation). At the heart of this is the measurement of Ys and it is
      demonstrated in this paper that this can be accomplished by studying the target
      in a simple (acoustically unaltered) in-air laboratory environment. The target
      chosen in this study is a thick spherical shell that was illuminated by a nearly
      spatially isotropic array of remote loudspeakers. Ys is constructed from ensemble
      averages of the cross-correlations of eight collocated accelerometers and
      microphones placed on the surface of the object. The structural admittance
      determined from the data showed excellent agreement with theory.

PMID- 28764454
TI  - Simulating the Chan-Hudspeth experiment on an active excised cochlear segment.
AB  - Hearing relies on a series of coupled electrical, acoustical, and mechanical
      interactions inside the cochlea that enable sound processing. The local
      structural and electrical properties of the organ of Corti (OoC) and basilar
      membrane give rise to the global, coupled behavior of the cochlea. However, it is
      difficult to determine the root causes of important behavior, such as the
      mediator of active processes, in the fully coupled in vivo setting. An
      alternative experimental approach is to use an excised segment of the cochlea
      under controlled electrical and mechanical conditions. Using the excised cochlear
      segment experiment conducted by Chan and Hudspeth [Nat. Neurosci. 8, 149-155
      (2005); Biophys. J. 89, 4382-4395 (2005)] as the model problem, a quasilinear
      computational model for studying the active in vitro response of the OoC to
      acoustical stimulation was developed. The model of the electrical, mechanical,
      and acoustical conditions of the experimental configuration is able to replicate
      some of the experiment results, such as the shape of the frequency response of
      the sensory epithelium and the variation of the resonance frequency with the
      added fluid mass. As in the experiment, the model predicts a phase accumulation
      along the segment. However, it was found that the contribution of this phase
      accumulation to the dynamics is insignificant. Taking advantage of the relative
      simplicity of the fluid loading, the three-dimensional fluid dynamics was reduced
      into an added mass loading on the OoC thereby reducing the overall complexity of
      the model.

PMID- 28764456
TI  - Binaural masking release in symmetric listening conditions with spectro
      temporally modulated maskers.
AB  - Speech reception thresholds (SRTs) decrease as target and maskers are spatially
      separated (spatial release from masking, SRM). The current study systematically
      assessed how SRTs and SRM for a frontal target in a spatially symmetric masker
      configuration depend on spectro-temporal masker properties, the availability of
      short-time interaural level difference (ILD) and interaural time difference
      (ITD), and informational masking. Maskers ranged from stationary noise to single,
      interfering talkers and were modified by head-related transfer functions to
      provide: (i) different binaural cues (ILD, ITD, or both) and (ii) independent
      maskers in each ear ("infinite ILD"). Additionally, a condition was tested in
      which only information from short-time spectro-temporal segments of the ear with
      a favorable signal-to-noise ratio (better-ear glimpses) was presented. For noise
      based maskers, ILD, ITD, and spectral changes related to masker location
      contributed similarly to SRM, while ILD cues played a larger role if temporal
      modulation was introduced. For speech maskers, glimpsing and perceived location
      contributed roughly equally and ITD contributed less. The "infinite ILD"
      condition might suggest better-ear glimpsing limitations resulting in a maximal
      SRM of 12 dB for maskers with low or absent informational masking. Comparison to
      binaural model predictions highlighted the importance of short-time processing
      and helped to clarify the contribution of the different binaural cues and
      mechanisms.

PMID- 28764457
TI  - A hybrid deconvolution approach to separate acoustic sources in multiple motion
      modes.
AB  - Motion mode is defined as a characteristic motion that a group of sources follow.
      If there are multiple groups of sources moving in the corresponding multiple
      motion modes, the beamforming map for a certain group of sources will be
      contaminated by the leakages from the other groups of sources. The original
      beamforming or deconvolution approaches fail to interpret the acoustic maps, as
      the source leakages may be mistaken for actual sources. A hybrid deconvolution
      approach is proposed to restrain the source leakages, so as to separate the
      acoustic sources in multiple motion modes. This approach simultaneously considers
      all the sources in the potential motion modes, and introduces equivalent sources
      in the corresponding motion modes to represent the sources. The equivalence
      between the actual sources and the equivalent sources leads to the construction
      of an expanded linear matrix equation. The sources in the respective motion modes
      are simultaneously extracted by solving the equation. The approach is shown
      effective by two numerical simulations and a practical experiment on two counter
      rotating sources and one static source.

PMID- 28764458
TI  - Characterization of phased array-steered acoustic vortex beams.
AB  - Acoustic vortex (AV) beams generation is a subject of current interest. Even
      though different applications have been proposed using AV, their potential of use
      is still to be explored. Recent research works on particle manipulation use
      phased array systems for AV generation because it allows a flexible beam
      configuration, i.e., the beam can be easily focalized and modified in its shape.
      However, little attention has been paid to the fact that the AV can also be
      electronically steered. In view of this, this work presents a study of the
      steering capability of an AV. In particular, this paper gives an analysis of the
      effect of the applied delay law on the structure of AV beams steered at different
      angles using an array transducer of 32 equidistant elements, deployed on a
      triangular lattice, operating at 40 kHz. Special attention is paid to the
      appearance of grating vortices. The effect of the individual element directivity
      on the resultant beam is also studied. Experimental measurements were carried out
      in order to validate numerical estimations. Obtained results paves the way for
      the use of electronically steered vortices in different applications. Also, the
      potential of use of acoustic grating vortices is discussed.

PMID- 28764459
TI  - Electrically conductive synthetic vocal fold replicas for voice production
      research.
AB  - A method of fabricating electrically conductive synthetic vocal fold replicas and
      monitoring their vibration via resistance measurement is presented. Normally non
      conductive silicone replicas were coated with conductive graphite and subjected
      to long-term vibration tests. Synchronized resistance and imaging data using
      hemilarynx and full larynx configurations showed an inverse correlation between
      replica contact area and resistance during vibration, similar to clinical
      electroglottography (EGG) used to estimate vocal fold contact area. This method
      has potential for long-term replica vibration monitoring and studying basic
      physical relationships between resistance and contact area in vocal folds and
      vocal fold replicas.

PMID- 28764462
TI  - Radiation damping of, and scattering from, an arbitrarily shaped bubble.
AB  - The work by Strasberg on small volume oscillations of bubbles with arbitrary
      shape [J. Acoust. Soc. Am. 25, 536-537 (1953)] is here extended to include the
      effects of radiation damping. An expression for the far-field scattering
      amplitude from an arbitrarily shaped bubble is given in terms of a quantity that
      is mathematically equivalent to the electrostatic capacitance of the bubble
      shape. This general approach is then applied to prolate and oblate spheroidal
      geometries, for which simple analytic expressions are available for the
      electrostatic capacitance, and the resulting far-field scattering amplitudes are
      compared to previous work in the literature.

PMID- 28764460
TI  - Recognition of asynchronous auditory-visual speech by younger and older
      listeners: A preliminary study.
AB  - This study examined the effects of age and hearing loss on recognition of speech
      presented when the auditory and visual speech information was misaligned in time
      (i.e., asynchronous). Prior research suggests that older listeners are less
      sensitive than younger listeners in detecting the presence of asynchronous speech
      for auditory-lead conditions, but recognition of speech in auditory-lead
      conditions has not yet been examined. Recognition performance was assessed for
      sentences and words presented in the auditory-visual modalities with varying
      degrees of auditory lead and lag. Detection of auditory-visual asynchrony for
      sentences was assessed to verify that listeners detected these asynchronies. The
      listeners were younger and older normal-hearing adults and older hearing-impaired
      adults. Older listeners (regardless of hearing status) exhibited a significant
      decline in performance in auditory-lead conditions relative to visual lead,
      unlike younger listeners whose recognition performance was relatively stable
      across asynchronies. Recognition performance was not correlated with asynchrony
      detection. However, one of the two cognitive measures assessed, processing speed,
      was identified in multiple regression analyses as contributing significantly to
      the variance in auditory-visual speech recognition scores. The findings indicate
      that, particularly in auditory-lead conditions, listener age has an impact on the
      ability to recognize asynchronous auditory-visual speech signals.

PMID- 28764463
TI  - An evaluation of several methods for computing lingual coarticulatory resistance
      using ultrasound.
AB  - The paper evaluates the efficiency of six computation methods in distinguishing
      lingual coarticulatory resistance among consonants and vowels using ultrasound
      data. This research goal is tested on a corpus of symmetrical vowel-consonant
      vowel sequences composed of 10 consonants and five vowels produced by five
      Catalan speakers. Results show that, while the coarticulatory resistance
      hierarchies obtained by all methods conform largely to the predictions of the
      degree of articulatory constraint model of coarticulation, some (i.e., area of
      the articulatory zone, mean point-by-point coefficient of variation, and mean
      nearest neighbour distance) are somewhat more highly predictive than others
      (i.e., locus equation, mutual information, and highest point of the tongue
      dorsum). Methods differ mostly regarding the classification of consonants
      exhibiting intermediate degrees of coarticulatory resistance due to the way the
      methods have been designed. The implications of these findings for research on
      dialectal variation are discussed.

PMID- 28764464
TI  - The devil is in the detail: Quantifying vocal variation in a complex, multi
      levelled, and rapidly evolving display.
AB  - Identifying and quantifying variation in vocalizations is fundamental to
      advancing our understanding of processes such as speciation, sexual selection,
      and cultural evolution. The song of the humpback whale (Megaptera novaeangliae)
      presents an extreme example of complexity and cultural evolution. It is a long,
      hierarchically structured vocal display that undergoes constant evolutionary
      change. Obtaining robust metrics to quantify song variation at multiple scales
      (from a sound through to population variation across the seascape) is a
      substantial challenge. Here, the authors present a method to quantify song
      similarity at multiple levels within the hierarchy. To incorporate the complexity
      of these multiple levels, the calculation of similarity is weighted by
      measurements of sound units (lower levels within the display) to bridge the gap
      in information between upper and lower levels. Results demonstrate that the
      inclusion of weighting provides a more realistic and robust representation of
      song similarity at multiple levels within the display. This method permits robust
      quantification of cultural patterns and processes that will also contribute to
      the conservation management of endangered humpback whale populations, and is
      applicable to any hierarchically structured signal sequence.

PMID- 28764465
TI  - Enhancing monochromatic multipole emission by a subwavelength enclosure of
      degenerate Mie resonances.
AB  - Sound emission is inefficient at low frequencies as limited by source size. This
      letter presents enhancing emission of monochromatic monopole and multipole
      sources by enclosing the source with a subwavelength circular enclosure filled of
      an anisotropic material of a low radial sound speed. The anisotropy is associated
      with an infinite tangential density along the azimuth. Numerical simulations show
      that emission gain is produced at frequencies surrounding degenerate Mie resonant
      frequencies of the enclosure, and meanwhile the radiation directivity pattern is
      well preserved. The degeneracy is theoretically analyzed. A realization of the
      material is suggested by using a space-coiling structure.

PMID- 28764466
TI  - A multi-wave elastic metamaterial based on degenerate local resonances.
AB  - In this letter, an experimental and numerical study of the influence of symmetric
      resonators on Lamb waves that propagate in a thin metallic plate is reported. The
      resonators consist of a set of small, closely packed rods that pass through the
      plate from side to side to create a locally resonant metamaterial. Adjusting the
      symmetry of these rods creates degenerate flexural resonances that can be tuned
      to couple only with a given Lamb mode that is either symmetric (S0) or anti
      symmetric (A0). This approach offers promising perspectives in the development of
      metamaterials for elastic waves that involve non-scalar interactions.

PMID- 28764467
TI  - Spectral analysis of bistatic scattering from underwater elastic cylinders and
      spheres.
AB  - Far field sound scattering from underwater elastic spheres and finite cylinders
      is considered over the full range of scattering angles. Three models for the
      frequency response of the scattered field are evaluated: a hybrid finite
      element/propagation simulation for a finite cylinder with broadside illumination,
      an approximate solution for the finite cylinder, and the exact solution for a
      sphere. The cylinder models are shown to give comparable results, attesting to
      the strength of the finite cylinder approximate solution. Interference and
      resonance structure present in the frequency response of the targets is
      identified and discussed, and the bistatic spectra for a variety of elastic
      sphere materials are presented. A thorough understanding of the complicated angle
      and frequency dependence of the scattering from simple elastic targets is helpful
      for interpretation of backscattering data from targets at or near an interface,
      or for scattering data taken by moving automated underwater vehicles, acoustic
      arrays, or other forms of data collection involving bistatic scattering.

PMID- 28764468
TI  - Automatic sociophonetics: Exploring corpora with a forensic accent recognition
      system.
AB  - This paper demonstrates how the Y-ACCDIST system, the York ACCDIST-based
      automatic accent recognition system [Brown (2015). Proceedings of the
      International Congress of Phonetic Sciences, Glasgow, UK], can be used to inspect
      sociophonetic corpora as a preliminary "screening" tool. Although Y-ACCDIST's
      intended application is to assist with forensic casework, the system can also be
      exploited in sociophonetic research to begin unpacking variation. Using a subset
      of the PEBL (Panjabi-English in Bradford and Leicester) corpus, the outputs of Y
      ACCDIST are explored, which, it is argued, efficiently and objectively assess
      speaker similarities across different linguistic varieties. The ways these
      outputs corroborate with a phonetic analysis of the data are also discovered.
      First, Y-ACCDIST is used to classify speakers from the corpus based on language
      background and region. A Y-ACCDIST cluster analysis is then implemented, which
      groups speakers in ways consistent with more localised networks, providing a
      means of identifying potential communities of practice. Additionally, the results
      of a Y-ACCDIST feature selection task that indicates which specific phonemes are
      most valuable in distinguishing between speaker groups are presented. How Y
      ACCDIST outputs can be used to reinforce more traditional sociophonetic analyses
      and support qualitative interpretations of the data is demonstrated.

PMID- 28764469
TI  - Numerical simulation of wave-induced fluid flow seismic attenuation based on the
      Cole-Cole model.
AB  - The acoustic behavior of porous media can be simulated more realistically using a
      stress-strain relation based on the Cole-Cole model. In particular, seismic
      velocity dispersion and attenuation in porous rocks is well described by
      mesoscopic-loss models. Using the Zener model to simulate wave propagation is a
      rough approximation, while the Cole-Cole model provides an optimal description of
      the physics. Here, a time-domain algorithm is proposed based on the Grunwald
      Letnikov numerical approximation of the fractional derivative involved in the
      time-domain representation of the Cole-Cole model, while the spatial derivatives
      are computed with the Fourier pseudospectral method. The numerical solution is
      successfully tested against an analytical solution. The methodology is applied to
      a model of saline aquifer, where carbon dioxide (CO2) is injected. To follow the
      migration of the gas and detect possible leakages, seismic monitoring surveys
      should be carried out periodically. To this aim, the sensitivity of the seismic
      method must be carefully assessed for the specific case. The simulated test
      considers a possible leakage in the overburden, above the caprock, where the
      sandstone is partially saturated with gas and brine. The numerical examples
      illustrate the implementation of the theory.

PMID- 28764470
TI  - Global loudness of rising- and falling-intensity tones: How temporal profile
      characteristics shape overall judgments.
AB  - The mechanisms underlying global loudness judgments of rising- or falling
      intensity tones were further investigated in two magnitude estimation
      experiments. By manipulating the temporal characteristics of such stimuli, it was
      examined whether judgments could be accounted for by an integration of their
      loudest portion over a certain temporal window associated to a "decay mechanism"
      downsizing this integration over time for falling ramps. In experiment 1, 1-kHz
      intensity-ramps were stretched in time between 1 and 16 s keeping their dynamics
      (difference between maximum and minimum levels) unchanged. While global loudness
      of rising tones increased up to 6 s, evaluations of falling tones increased at a
      weaker rate and slightly decayed between 6 and 16 s, resulting in significant
      differences between the two patterns. In experiment 2, ramps were stretched in
      time between 2 and 12 s keeping their slopes (rate of change in dB/s) unchanged.
      In this context, the main effect of duration became non-significant and the
      interaction between the two profiles remained, although the decay of falling
      tones was not significant. These results qualitatively support the view that the
      global loudness computation of intensity-ramps involves an integration of their
      loudest portions; the presence of a decay mechanism could, however, not be
      attested.

PMID- 28764471
TI  - Corpus of deaf speech for acoustic and speech production research.
AB  - A corpus of recordings of deaf speech is introduced. Adults who were pre- or post
      lingually deafened as well as those with normal hearing read standardized speech
      passages totaling 11 h of .wav recordings. Preliminary acoustic analyses are
      included to provide a glimpse of the kinds of analyses that can be conducted with
      this corpus of recordings. Long term average speech spectra as well as spectral
      moment analyses provide considerable insight into differences observed in the
      speech of talkers judged to have low, medium, or high speech intelligibility.

PMID- 28764472
TI  - Spectral moments vs discrete cosine transformation coefficients: Evaluation of
      acoustic measures distinguishing two merging German fricatives.
AB  - The results of the quantification of the acoustic differences between German /c/
      and /?/ in three speaker groups with varying contrast realizations are presented.
      Data for two speaker groups were collected in Berlin and Kiel, where the contrast
      is still realized. Data for a third group were collected in Berlin from speakers
      of Hood German-a youth-style multiethnolect spoken by adolescents in multilingual
      and multicultural neighborhoods of Berlin-where the contrast has weakened or is
      even lost. A forced choice perception test showed that listeners reliably
      differentiate these two fricatives in minimal pairs produced by the speakers from
      Berlin and Kiel, but fail to do so for the productions of the Hood German
      speakers. The acoustic analysis reveals that spectrally, the fricatives are very
      similar in all varieties. The spectral moments (Center of Gravity, standard
      deviation, kurtosis, skewness) fail to reveal the differences between the
      fricatives that are apparent from visual inspection of the spectra and the
      perceived auditory differences. Analyses of the discrete cosine transformation
      coefficients, however, better quantify these differences. This study suggests
      that minute differences between fricatives that vary between speaker groups may
      be captured more reliably with discrete cosine transformations compared to
      spectral moments.

PMID- 28764473
TI  - Combining the remote microphone technique with head-tracking for local active
      sound control.
AB  - This paper describes practical integration of the remote microphone technique
      with a head-tracking device in a local active noise control system. The
      formulation is first reviewed for the optimized observation filter and nearfield
      pressure estimation. The attenuation performance and stability of an adaptive
      active headrest system combined with the remote microphone technique are then
      studied. The accuracy of the nearfield estimation and the effect of the head
      tracking on the control performance are investigated in real-time experiments.
      The regularization factor of the observation filter is selected as a trade-off
      between its accuracy and its robustness. The integrated active headrest system is
      used to estimate and attenuate disturbance signals at a listener's ears from a
      single tonal primary source, while a commercial head-tracking device detects and
      provides the real-time head position to the active headrest system whose
      responses are updated accordingly.

PMID- 28764474
TI  - The effect of permutations of time samples in the speech waveform on
      intelligibility.
AB  - This paper describes the effect of two types of temporal permutations of the
      speech waveform on speech intelligibility. Using an overlap-add procedure with
      triangular-shaped windows for frame lengths of 1/8 to 2048 ms, the temporal order
      of the speech samples within each frame was subjected to either of two types of
      permutations: time-reversal or randomization. For both permutations, speech
      intelligibility tests expectantly show 100% intelligibility for the very short
      frame lengths containing only a few speech samples. Intelligibility drops to
      essentially zero toward longer frame lengths of around 1 ms. Interestingly, only
      for the reverse condition, intelligibility recovers to essentially 100% for frame
      lengths in the 4-32 ms range, dropping again to zero for frame lengths exceeding
      about 100 ms. Tests for the Japanese and the English language show essentially
      similar results. The data are interpreted along the lines of a previous paper by
      Kazama and the present authors [J. Acoust. Soc. Am. 127(3), 1432-1439 (2010)]. As
      in that previous paper, the loss of temporal envelope correlation shows a pattern
      very similar to that of the intelligibility data, illustrating again the
      importance of the preservation of narrow-band envelopes for speech
      intelligibility.

PMID- 28764475
TI  - Optimization of natural frequencies of a plate structure by modifying boundary
      conditions.
AB  - A combined approach based on finite element method and genetic algorithm (FEM-GA)
      is proposed for optimizing the natural frequencies of plate structures. This
      approach can identify the optimal boundary conditions so that the plate's natural
      frequencies can be adjusted simultaneously to their corresponding target values.
      In this approach, the natural frequencies of plates with arbitrary boundary
      conditions are calculated by FEM, while GA is employed for searching the optimal
      solutions of the multiple-objective optimization problem. The FEM is validated by
      comparing with previous results. The proposed approach is illustrated by
      numerical examples. The results demonstrate the effectiveness of this approach.

PMID- 28764476
TI  - Durational compensation within a CV mora in spontaneous Japanese: Evidence from
      the Corpus of Spontaneous Japanese.
AB  - Previous experimental studies showed that in Japanese, vowels are longer after
      shorter onset consonants; there is durational compensation within a CV-mora. In
      order to address whether this compensation occurs in natural speech, this study
      re-examines this observation using the Corpus of Spontaneous Japanese. The
      results, which are based on more than 200 000 CV-mora tokens, show that there is
      a negative correlation between the onset consonant and the following vowel in
      terms of their duration. The statistical significance of this negative
      correlation is assessed by a traditional correlation analysis as well as a
      bootstrap resampling analysis, which both show that it is unlikely that the
      observed compensation effect occurred by chance. The compensation is not perfect,
      however, suggesting that it is a stochastic tendency rather than an absolute
      principle. This paper closes with a discussion of potential factors that may
      interact with the durational compensation effect.

PMID- 28764477
TI  - Incipient fault diagnosis in bearings under variable speed conditions using
      multiresolution analysis and a weighted committee machine.
AB  - Incipient defects in bearings are traditionally diagnosed either by developing
      discriminative models for features that are extracted from raw acoustic emission
      (AE) signals, or by detecting peaks at characteristic defect frequencies in the
      envelope power spectrum of the AE signals. Under variable speed conditions,
      however, such methods do not yield the best results. This letter proposes a
      technique for diagnosing incipient bearing defects under variable speed
      conditions, by extracting features from different sub-bands of the inherently non
      stationary AE signal, and then classifying bearing defects using a weighted
      committee machine, which is an ensemble of support vector machines and artificial
      neural networks. The proposed method also improves the generalization performance
      of the neural networks to enhance their classification accuracy, particularly
      with limited training data.

PMID- 28764478
TI  - Variation in echolocation call frequencies in two species of free-tailed bats
      according to temperature and humidity.
AB  - Bats can actively adjust their echolocation signals to specific habitats and
      tasks, yet it is not known if bats also modify their calls to decrease
      atmospheric attenuation. Here the authors test the hypothesis that individuals
      emit echolocation calls ideally suited to current conditions of temperature and
      humidity. The authors recorded two species, Molossus molossus and Molossops
      temminckii, in the field under different conditions of humidity and temperature.
      For each species, two calls were analyzed: the shorter frequency modulated (FM)
      signals that bats emitted as they approached the recording microphone, and the
      longer constant frequency (CF) calls emitted thereafter. For each signal, the
      authors extracted peak frequency and duration, and compared these parameters
      among species, call type, and environmental conditions. The authors' results show
      significant differences in peak frequency and duration among environmental
      conditions for both call types. Bats decreased the frequency and increased
      duration of CF calls as atmospheric attenuation increased; using a lower
      frequency call may increase the range of detection by a few meters as atmospheric
      attenuation increases. The same trend was not observed for FM calls, which may be
      explained by the primary role of these signals in short-range target
      localization.

PMID- 28764479
TI  - Analyzing dialect variation in historical speech corpora.
AB  - The Linguistic Atlas of the Gulf States is an extensive audio corpus of
      sociolinguistic interviews with 1121 speakers from eight southeastern U.S.
      states. Complete interviews have never been fully transcribed, leaving a wealth
      of phonetic information unexplored. This paper details methods for large-scale
      acoustic analysis of this historical speech corpus, providing a fuller picture of
      Southern speech than offered by previous impressionistic analyses. Interviews
      from 10 speakers (~36 h) in southeast Georgia were transcribed and analyzed for
      dialectal features associated with the Southern Vowel Shift and African American
      Vowel Shift, also considering the effects of age, gender, and race. Multiple
      tokens of common words were annotated (N = 6085), and formant values of their
      stressed vowels were extracted. The effects of shifting on relative vowel
      placement were evaluated via Pillai scores, and vowel dynamics were estimated via
      functional data analysis and modeled with linear mixed-effects regression.
      Results indicate that European American speakers show features of the Southern
      Vowel Shift, though certain speakers shift in more ways than others, and African
      American speakers' productions are consistent with the African American Vowel
      Shift. Wide variation is apparent, even within this small geographic region,
      contributing evidence of the complexity of Southern speech.

PMID- 28764480
TI  - High frequency ultrasound imaging and simulations of sea urchin oocytes.
AB  - High frequency ultrasound backscatter signals from sea urchin oocytes were
      measured using a 40 MHz transducer and compared to numerical simulations. The
      Faran scattering model was used to calculate the ultrasound scattered from single
      oocytes in suspension. The urchin oocytes are non-nucleated with uniform size and
      biomechanical properties; the backscatter from each cell is similar and easy to
      simulate, unlike typical nucleated mammalian cells. The time domain signal
      measured from single oocytes in suspension showed two distinct peaks, and the
      power spectrum was periodic with minima spaced approximately 10 MHz apart. Good
      agreement to the Faran scattering model was observed. Measurements from tightly
      packed oocyte cell pellets showed similar periodic features in the power spectra,
      which was a result of the uniform size and consistent biomechanical properties of
      the cells. Numerical simulations that calculated the ultrasound scattered from
      individual oocytes within a three dimensional volume showed good agreement to the
      measured signals and B-scan images. A cepstral analysis of the signal was used to
      calculate the size of the cells, which was 78.7 MUm (measured) and 81.4 MUm
      (simulated). This work supports the single scattering approximation, where
      ultrasound is discretely scattered from single cells within a bulk homogeneous
      sample, and that multiple scattering has a negligible effect. This technique can
      be applied towards understanding the complex scattering behaviour from
      heterogeneous tissues.

PMID- 28764481
TI  - Numerical investigation of cavity self-oscillation and noise radiation induced by
      turbulent flow at non-zero inclination angle.
AB  - A hybrid numerical approach was used on a three-dimensional cavity at a non-zero
      inclination angle of the upstream section to reveal the mechanism of self
      oscillation and the characteristics of far-field sound field. In this hybrid
      approach, the unsteady flow physics was captured by a compressible large eddy
      simulation, and the far-field sound field was calculated by the FW-H integral
      equation, with the noise source provided by near-field calculation. The mechanism
      of self-oscillation was revealed based on the instantaneous flow field structure
      and the pressure inside the cavity. The effects of the position of opening,
      inclination angle and neck thickness on the frequency and amplitude of the
      fluctuation pressure inside the cavity were examined. Results showed that the
      frequency and the amplitude were sensitive to the inclination angle but not to
      the position of the opening. Under varying neck thicknesses, the fundamental
      frequencies changed, but the amplitude remained almost constant. The influences
      of the boundary layer thickness on the amplitude of the fluctuation pressure was
      also investigated. Results revealed that the oscillation was suppressed once the
      boundary layer thickness reached a critical value. The findings could provide a
      reference for a quiet car with a low sunroof buffeting noise.

PMID- 28764483
TI  - Estimation of the roll angle in a triplet towed array using oceanic surface
      generated ambient noise.
AB  - This paper proposes a roll-angle estimation method for the triplet towed array
      using the oceanic ambient noise recorded in the mid-frequency range of 1 to 10
      kHz. Here, the dominance of oceanic surface-generated noises such as wind-driven
      and shipping noises is expected. The ratio between the approximated phase parts
      of the noise-coherence function regarding the triplet hydrophones is used for the
      roll estimation. Advantage of this technique is that explicit input regarding the
      oceanic environment is not required, especially for an ocean with an azimuthally
      uniform noise field or dominant noise sources at the end-fire direction of the
      horizontal array. In other cases, a roll-angle bias occurs depending on the
      horizontal directionality. This proposed technique is applied to ocean-ambient
      noise measurements that were collected in the East Sea of Korea during August
      2015. The roll angles of the triplet array are estimated from the measurements
      and compared with roll-sensor-measured data. The estimated roll angles agree with
      the measured ones within the root mean square error of 10 degrees , and their
      difference tends to decrease with increasing wind speed.

PMID- 28764482
TI  - Strength of onset and ongoing cues in judgments of lateral position.
AB  - This study describes the contributions to auditory image position of an
      interaural time delay (ITD) cue at onset relative to subsequent ITDs during the
      ongoing part of a stimulus. Test stimuli were trains of 1-ms binaural noise
      bursts; lateral position was measured with a wideband acoustic pointer that
      subjects adjusted to match the intracranial position of test stimuli. In
      different conditions the ongoing part of the stimulus (the bursts following the
      first one) either had a consistent ITD (the same ITD on each ongoing burst), or
      had alternating leading and lagging components with ITDs that opposed one
      another. As duration of the ongoing part was increased from 4 to 250 ms, with the
      initial ITD fixed, lateral position changed from being dominated by the onset ITD
      to being dominated by the ongoing consistent or leading ITD. With alternating
      ongoing ITDs equal contributions from onset and ongoing parts were obtained at an
      ongoing duration of about 40 ms; with consistent ongoing ITDs equal contributions
      were obtained at about 15 ms. The results point up the increased dominance of
      onset cues when ongoing cues are ambiguous, as they often are in real-world
      settings.

PMID- 28764484
TI  - Beyond lexical meaning: The effect of emotional prosody on spoken word
      recognition.
AB  - This study employs an auditory-visual associative priming paradigm to test
      whether non-emotional words uttered in emotional prosody (e.g., pineapple spoken
      in angry prosody or happy prosody) facilitate recognition of semantically
      emotional words (e.g., mad, upset or smile, joy). The results show an affective
      priming effect between emotional prosody and emotional words independent of
      lexical carriers of the prosody. Learned acoustic patterns in speech (e.g.,
      emotional prosody) map directly to social concepts and representations, and this
      social information influences the spoken word recognition process.

PMID- 28764485
TI  - Reconceptualizing the vowel space in analyzing regional dialect variation and
      sound change in American English.
AB  - Vowel space area (VSA) calculated on the basis of corner vowels has emerged as a
      metric for the study of regional variation, speech intelligibility and speech
      development. This paper gives an evaluation of the basic assumptions underlying
      both the concept of the vowel space and the utility of the VSA in making cross
      dialectal and sound change comparisons. Using cross-generational data from 135
      female speakers representing three distinct dialects of American English, the
      first step was to establish that the vowel quadrilateral fails as a metric in the
      context of dialect variation. The next step was to examine the efficacy of more
      complete assessments of VSA represented by the convex hull and the concave hull.
      Despite the improvement over the quadrilateral, both metrics yielded inconsistent
      estimates of VSA. This paper then explores the possibility that regional
      variation can be characterized more effectively if formant dynamics and the
      resulting spectral overlap were also considered in defining the space. The
      proposed formant density approach showed that the working space may be common to
      all dialects but the differences are in the internal distribution of spectral
      density regions that define dialect-specific "usage" of the acoustic space. The
      dialect-inherent distribution of high and low density regions is largely shaped
      by sound change.

PMID- 28764486
TI  - Robust reproduction of sound zones with local sound orientation.
AB  - Pressure matching (PM) and planarity control (PC) methods can be used to
      reproduce local sound with a certain orientation at the listening zone, while
      suppressing the sound energy at the quiet zone. In this letter, regularized PM
      and PC, incorporating coarse error estimation, are introduced to increase the
      robustness in non-ideal reproduction scenarios. Facilitated by this, the
      interaction between regularization, robustness, (tuned) personal audio
      optimization, and local directional performance is explored. Simulations show
      that under certain conditions, PC and weighted PM achieve comparable performance,
      while PC is more robust to a poorly selected regularization parameter.

PMID- 28764487
TI  - A technique based on droplet evaporation to recognize alcoholic drinks.
AB  - Chromatography is, at present, the most used technique to determine the purity of
      alcoholic drinks. This involves a careful separation of the components of the
      liquid elements. However, since this technique requires sophisticated
      instrumentation, there are alternative techniques such as conductivity
      measurements and UV-Vis and infrared spectrometries. We report here a method
      based on salt-induced crystallization patterns formed during the evaporation of
      alcoholic drops. We found that droplets of different samples form different
      structures upon drying, which we characterize by their radial density profiles.
      We prove that using the dried deposit of a spirit as a control sample, our method
      allows us to differentiate between pure and adulterated drinks. As a proof of
      concept, we study tequila.

PMID- 28764488
TI  - A compact dispersive refocusing Rowland circle X-ray emission spectrometer for
      laboratory, synchrotron, and XFEL applications.
AB  - X-ray emission spectroscopy is emerging as an important complement to x-ray
      absorption fine structure spectroscopy, providing a characterization of the
      occupied electronic density of states local to the species of interest. Here, we
      present details of the design and performance of a compact x-ray emission
      spectrometer that uses a dispersive refocusing Rowland (DRR) circle geometry to
      achieve excellent performance for the 2-2.5 keV range, i.e., especially for the K
      edge emission from sulfur and phosphorous. The DRR approach allows high energy
      resolution even for unfocused x-ray sources. This property enables high count
      rates in laboratory studies, approaching those of insertion-device beamlines at
      third-generation synchrotrons, despite use of only a low-powered, conventional x
      ray tube. The spectrometer, whose overall scale is set by use of a 10-cm diameter
      Rowland circle and a new small-pixel complementary metal-oxide-semiconductor x
      ray camera, is easily portable to synchrotron or x-ray free electron laser
      beamlines. Photometrics from measurements at the Advanced Light Source show
      excellent overall instrumental efficiency. In addition, the compact size of this
      instrument lends itself to future multiplexing to gain large factors in net
      collection efficiency or its implementation in controlled gas gloveboxes either
      in the lab or in an endstation.

PMID- 28764489
TI  - Hysteresis compensation of the Prandtl-Ishlinskii model for piezoelectric
      actuators using modified particle swarm optimization with chaotic map.
AB  - Piezoelectric actuators invariably exhibit hysteresis nonlinearities that tend to
      become significant under the open-loop condition and could cause oscillations and
      errors in nanometer-positioning tasks. Chaotic map modified particle swarm
      optimization (MPSO) is proposed and implemented to identify the Prandtl
      Ishlinskii model for piezoelectric actuators. Hysteresis compensation is attained
      through application of an inverse Prandtl-Ishlinskii model, in which the
      parameters are formulated based on the original model with chaotic map MPSO. To
      strengthen the diversity and improve the searching ergodicity of the swarm, an
      initial method of adaptive inertia weight based on a chaotic map is proposed. To
      compare and prove that the swarm's convergence occurs before stochastic
      initialization and to attain an optimal particle swarm optimization algorithm,
      the parameters of a proportional-integral-derivative controller are searched
      using self-tuning, and the simulated results are used to verify the search
      effectiveness of chaotic map MPSO. The results show that chaotic map MPSO is
      superior to its competitors for identifying the Prandtl-Ishlinskii model and that
      the inverse Prandtl-Ishlinskii model can provide hysteresis compensation under
      different conditions in a simple and effective manner.

PMID- 28764490
TI  - Note: Mechanical in situ exfoliation of van der Waals materials.
AB  - Exfoliation, namely, the peeling of layered materials down to a single unit-cell
      thin foil, opens promising avenues to fabricate novel electronic materials. New
      properties and original functionalities emerge in the single and few layer
      configurations of a number of layered compounds, in particular in transition
      metal dichalcogenides. However, many of these thin exfoliated materials are very
      sensitive to ambient conditions impeding the exploration of this new and
      fascinating parameter space. Here we describe a method of mechanical exfoliation
      in ultra-high vacuum (UHV). This technique is easily adaptable to any UHV system
      and allows preparing and studying air sensitive nanoflakes in situ. We present
      the basic design and proof-of-concept scanning tunneling microscopy imaging of
      VSe2 nanoflakes.

PMID- 28764491
TI  - Note: A high count rate real-time digital processing method for PGNAA data
      acquisition system.
AB  - The prompt gamma neutron activation analysis (PGNAA) technique is a real-time
      online method to analyze the composition of industrial materials. This paper
      presents a data acquisition system with a high count rate and real-time digital
      processing method for PGNAA. Limited by the decay time of the detector, the ORTEC
      multi-channel analyzer (MCA) can normally achieve an average count rate of 100
      kcps. However, this system uses an electrical technique to increase the average
      count rate and reduce dead time, and guarantees good accuracy. Since the
      measuring time is usually limited to about 120 s, in order to accelerate the
      accumulation rate of spectrum and reduce the statistical error, the average count
      rate is expected to reach more than 500 kcps.

PMID- 28764492
TI  - Low noise current preamplifier for qPlus sensor deflection signal detection in
      atomic force microscopy at room and low temperatures.
AB  - The resolution of frequency modulation atomic force microscopy is limited by
      instrumental noise. When using a qPlus sensor, the deflection detector noise is
      the dominant noise contribution. It can be reduced by improving the preamplifier
      used to amplify the sensor deflection signal. We present a simple single-stage
      differential preamplifier which outperforms previous designs known to us by at
      least a factor of two in the deflection noise density. We show specific versions
      of this preamplifier to use in ambient conditions, in ultra-high vacuum at room
      temperature, and at 4.2 K. Furthermore, we compare the thermal peak analysis and
      the frequency shift noise density method as a means to determine the deflection
      noise density. We note that this preamplifier can also be used for any current
      generating sensors such as other piezoelectric sensors and photodiodes, but, in
      this paper, we restrict our analysis to qPlus sensors.

PMID- 28764493
TI  - Diffractive refractometer for liquid characterization and transient processes
      monitoring.
AB  - A simple refractometer using a reflective diffraction grating immersed in the
      test liquid is developed and its performance is studied. Due to the dependence of
      the light wavelength on the refractive index, determining the angle of the
      diffracted beam provides the refractive index of the liquid. The glass cell
      containing the test liquid is cylindrical, and the grating plane is parallel to
      the cylinder symmetry axis. The light beam normally impinges on the cell front
      wall and reaches the center of the grating so that the diffracted beam leaves the
      cell without being deviated by refraction. It is demonstrated that this
      characteristic of the optical setup minimizes important error sources due to
      undesired beam deviations and enables real-time refractive index measurement of
      liquids in transient processes. Moreover, the performances of the diffractive
      refractometer and of a commercial Abbe refractometer are compared in the
      measurement of the refractive indexes of aqueous NaCl solutions. A He-Ne laser at
      632.8 nm is used as a light source, and the diffraction grating has 1200
      lines/mm. Measurement precisions of the order of 8 * 10-4 are achieved.

PMID- 28764494
TI  - Bio-inspired piezoelectric linear motor driven by a single-phase harmonic wave
      with an asymmetric stator.
AB  - A novel, bio-inspired, single-phase driven piezoelectric linear motor (PLM) using
      an asymmetric stator was designed, fabricated, and tested to avoid mode
      degeneracy and to simplify the drive mechanism of a piezoelectric motor. A
      piezoelectric transducer composed of two piezoelectric stacks and a displacement
      amplifier was used as the driving element of the PLM. Two simple and specially
      designed claws performed elliptical motion. A numerical simulation was performed
      to design the stator and determine the feasibility of the design mechanism of the
      PLM. Moreover, an experimental setup was built to validate the working
      principles, as well as to evaluate the performance, of the PLM. The prototype
      motor outputs a no-load speed of 233.7 mm/s at a voltage of 180 Vp-p and a
      maximum thrust force of 2.3 N under a preload of 10 N. This study verified the
      feasibility of the proposed design and provided a method to simplify the driving
      harmonic signal and structure of PLMs.

PMID- 28764495
TI  - Integral force feedback control with input shaping: Application to piezo-based
      scanning systems in ECDLs.
AB  - In this paper, a hybrid control system is developed by integrating the closed
      loop force feedback and input shaping method to overcome the problem of the
      hysteresis and dynamic behavior in piezo-based scanning systems and increase the
      scanning speed of tunable external cavity diode lasers. The flexible hinge and
      piezoelectric actuators are analyzed, and a dynamic model of the scanning systems
      is established. A force sensor and an integral controller are utilized in
      integral force feedback (IFF) to directly augment the damping of the
      piezoelectric scanning systems. Hysteresis has been effectively eliminated, but
      the mechanical resonance is still evident. Noticeable residual vibration occurred
      after the inflection points and then gradually disappeared. For the further
      control of mechanical resonance, based on the theory of minimum-acceleration
      trajectory planning, the time-domain input shaping method was developed. The
      turning sections of a scanning trajectory are replaced by smooth curves, while
      the linear sections are retained. The IFF method is combined with the input
      shaping method to control the non-linearity and mechanical resonance in high
      speed piezo-based scanning systems. Experiments are conducted, and the results
      demonstrate the effectiveness of the proposed control approach.

PMID- 28764496
TI  - Microcantilever array instrument based on optical fiber and performance analysis.
AB  - We developed a microcantilever array biosensor instrument based on optical
      readout from a microcantilever array in fluid environment. The microcantilever
      signals were read out sequentially by laser beams emitted from eight optical
      fibers. The optical fibers were coupled to lasers, while the other ends of the
      fibers were embedded in eight V-grooves with 250 MUm pitch microfabricated from a
      Si wafer. Aspherical lens was used to keep the distance between lasers. A
      programmable logic controller was used to make the system work stably. To make
      sure that the output of lasers was stable, a temperature controller was set up
      for each laser. When the deflection signal was collected, lasers used here were
      set to be on for at least 400 ms in each scanning cycle to get high signal-to
      noise ratio deflection curves. A test was performed by changing the temperature
      of the liquid cell holding a microcantilever array to verify the consistent
      response of the instrument to the cantilever deflections. The stability and
      conformance of the instrument were demonstrated by quantitative detection of
      mercury ions in aqueous solution and comparison detection of clenbuterol by
      setting test and reference cantilevers. This microcantilever array detection
      instrument can be applied to highly sensitive detection of chemical and
      biological molecules in fluid environment.

PMID- 28764497
TI  - Note: Infrared laser diagnostics for deuterium gas puff Z pinches.
AB  - Deuterium gas puff Z pinches have been used for generation of strong neutron
      fluxes on the MA class pulse power machines. Due to the low electron density of
      deuterium Z-pinch plasma, regular laser diagnostics in the visible range cannot
      be used for observation and study of the pinch. Laser probing at the wavelength
      of 1064 nm was used for visualization of deuterium plasma. Infrared schlieren and
      interferometry diagnostics showed the deuterium gas puff plasma dynamics,
      instabilities, and allowed for the reconstruction of the profile of the plasma
      density.

PMID- 28764498
TI  - Publisher's Note: "Preface: Focus on imaging methods in granular physics" [Rev.
      Sci. Instrum. 88, 051701 (2017)].

PMID- 28764499
TI  - Efficient procedure for the measurement of preresonant excitation profiles in UV
      Raman spectroscopy.
AB  - Resonance Raman spectroscopy (RRS) is a promising technique for investigating
      samples with low concentrations of single constituents or many different
      constituents. The wavelength dependent resonance enhancement (resonance profile)
      of the respective molecule yields information about the targeted species and
      reveals the optimal wavelength for high resolution RRS. A significant increase of
      the Raman scattered intensity can already be achieved in the vicinity of the
      molecules' absorption band (preresonance). Measuring such preresonance and
      resonance profiles requires precise control of excitation conditions and careful
      assessment of the spectral accuracy of the setup. We present a comprehensive
      procedure for the acquisition of preresonance profiles in Raman spectroscopy. An
      experimental setup for recording the single spectra is combined with an efficient
      algorithm for data postprocessing. The procedure is demonstrated on amino acids
      measured in the UV and can be applied to any molecule and wavelength range.

PMID- 28764500
TI  - Note: A four-pass acousto-optic modulator system for laser cooling of sodium
      atoms.
AB  - We present a four-pass acousto-optic modulator (AOM) system for providing the
      repumping light for laser cooling of sodium atoms. With only one 400 MHz AOM, we
      achieve a tunable laser frequency shift around 1.6 GHz with total efficiency up
      to 30%. This setup provides an alternative over conventional methods to generate
      a sodium repumping light using more expensive high frequency AOMs or electro
      optical modulators (EOMs) in the GHz domain. This compact and reliable setup can
      be easily adapted to other frequencies and may find applications in laser
      spectroscopy, laser cooling and trapping, and coherent manipulation of atomic
      quantum states.

PMID- 28764501
TI  - Note: Novel trigger pulse feed method for mega-volt gas switch.
AB  - It is difficult to feed the trigger pulse into an electrically triggered mega
      volt switch, and the present note presents a novel trigger pulse feed method. The
      trigger pulse is introduced via a damping resistor, which is mounted between the
      inner and outer cylindrical electrodes of the pulse transmission line. The mega
      volt pulse is damped because the voltage is resistively divided by the resistor
      and trigger cable arrangement. Both the complex breakdown processes of the switch
      and its insulation issues are experimentally studied. The function and the
      beneficial effects of the damping resistor, installed together with an additional
      inductor, are discussed. Finally, the parameters of these two damping components
      are set to 500 Omega and 2 MUH values for which the switch has been demonstrated
      to work successfully at over 2.3 MV.

PMID- 28764502
TI  - High gradient, high reliability, and low wakefield accelerating structures for
      the FERMI FEL.
AB  - The FERMI seeded free-electron laser (FEL), located at the Elettra laboratory in
      Trieste, is a 4th generation light source operating in the vacuum ultraviolet to
      soft X-rays range. The FEL design is based on an external seeding scheme which
      improves the output pulse coherence and the central wavelength control and
      reduces the spectral bandwidth. FERMI has achieved its original energy target by
      producing photon energies above 300 eV from a 1.50 GeV, 600 A peak current,
      electron beam. However, there is a strong scientific motivation to push the
      energy envelop further higher to photon energy up to 600 eV to cover both the x
      ray absorption edges of nitrogen K (400 eV) and oxygen K (532 eV). To achieve
      this goal, the electron beam energy will be increased from 1.50 GeV to 1.80 GeV
      and the peak beam current will be pushed towards 1 kA. This requires essentially
      the development of more reliable high gradient S-band accelerating structures,
      with low wakefields contribution up to 1 nC charge per bunch. Accordingly, in the
      following, we present the design of high gradient, high reliability, and low
      wakefield S-band accelerating structures for the upgrade program of the FERMI
      linac.

PMID- 28764503
TI  - Scintillator-based transverse proton beam profiler for laser-plasma ion sources.
AB  - A high repetition rate scintillator-based transverse beam profile diagnostic for
      laser-plasma accelerated proton beams has been designed and commissioned. The
      proton beam profiler uses differential filtering to provide coarse energy
      resolution and a flexible design to allow optimisation for expected beam energy
      range and trade-off between spatial and energy resolution depending on the
      application. A plastic scintillator detector, imaged with a standard 12-bit
      scientific camera, allows data to be taken at a high repetition rate. An
      algorithm encompassing the scintillator non-linearity is described to estimate
      the proton spectrum at different spatial locations.

PMID- 28764504
TI  - A high throughput instrument to measure mechanical losses in thin film coatings.
AB  - Brownian thermal noise generated by mechanical losses in thin film coatings
      limits the sensitivity of gravitational wave detectors, as well as several high
      precision metrology experiments. Improving the sensitivity of the next generation
      of gravitational wave detectors will require optical coatings with significantly
      reduced mechanical losses. In this paper, we describe a system that we developed
      to measure the mechanical loss angle of thin film coatings deposited on fused
      silica substrates. The novelty of this system resides in the capability of
      parallel measurement of up to four samples and the ability to simultaneously
      probe all the resonant modes of each sample. This high throughput measurement
      system allows the exploration of a large number of deposition and material
      parameters, which can be tuned to achieve low loss coatings.

PMID- 28764505
TI  - Velocity-space sensitivities of neutron emission spectrometers at the tokamaks
      JET and ASDEX Upgrade in deuterium plasmas.
AB  - Future fusion reactors are foreseen to be heated by the energetic alpha particles
      produced in fusion reactions. For this to happen, it is important that the
      energetic ions are sufficiently confined. In present day fusion experiments,
      energetic ions are primarily produced using external heating systems such as
      neutral beam injection and ion cyclotron resonance heating. In order to diagnose
      these fast ions, several different fast-ion diagnostics have been developed and
      implemented in the various experiments around the world. The velocity-space
      sensitivities of fast-ion diagnostics are given by so-called weight functions.
      Here instrument-specific weight functions are derived for neutron emission
      spectrometry detectors at the tokamaks JET and ASDEX Upgrade for the 2.45 MeV
      neutrons produced in deuterium-deuterium reactions in deuterium plasmas. Using
      these, it is possible to directly determine which part of velocity space each
      detector observes.

PMID- 28764506
TI  - Extended-bandwidth frequency sweeps of a distributed feedback laser using
      combined injection current and temperature modulation.
AB  - This article details the generation of an extended-bandwidth frequency sweep
      using a single, communication grade distributed feedback (DFB) laser. The
      frequency sweep is generated using a two-step technique. In the first step,
      injection current modulation is employed as a means of varying the output
      frequency of a DFB laser over a bandwidth of 99.26 GHz. A digital optical phase
      lock loop is used to lock the frequency sweep speed during current modulation,
      resulting in a linear frequency chirp. In the second step, the temperature of the
      DFB laser is modulated, resulting in a shifted starting laser output frequency. A
      laser frequency chirp is again generated beginning at this shifted starting
      frequency, resulting in a frequency-shifted spectrum relative to the first
      recorded data. This process is then repeated across a range of starting
      temperatures, resulting in a series of partially overlapping, frequency-shifted
      spectra. These spectra are then aligned using cross-correlation and combined
      using averaging to form a single, broadband spectrum with a total bandwidth of
      510.9 GHz. In order to investigate the utility of this technique, experimental
      testing was performed in which the approach was used as the swept-frequency
      source of a coherent optical frequency domain reflectometry system. This system
      was used to interrogate an optical fiber containing a 20 point, 1-mm pitch length
      fiber Bragg grating, corresponding to a period of 100 GHz. Using this technique,
      both the periodicity of the grating in the frequency domain and the individual
      reflector elements of the structure in the time domain were resolved,
      demonstrating the technique's potential as a method of extending the sweeping
      bandwidth of semiconductor lasers for frequency-based sensing applications.

PMID- 28764507
TI  - Broadband rectangular TEn0 mode exciter with H-plane power dividers for 100 GHz
      confocal gyro-devices.
AB  - A generic approach to excite TEn0 (n >= 1) modes in a rectangular waveguide for
      confocal gyro-devices is proposed. The exciter consists of a 3 dB H-plane power
      divider (n >= 3) and a mode-converting section. The injection power is split into
      two in-phase signals with equal amplitudes which simultaneously excite the
      secondary waveguide via two sets of multiple slots. Both the position and width
      of the slot are symmetrically distributed with respect to the center line for
      each set of slots. The slot width complies with a geometry sequence, with
      adjacent slots being spaced a quarter wavelength apart to cancel the backward
      wave out. A TE40 mode exciter at 100 GHz is numerically simulated and optimized,
      achieving a 1 dB and a 3 dB transmission bandwidth of 18.2 and 21 GHz,
      respectively. The prototype is fabricated and measured. The cold test is carried
      out utilizing two identical back-to-back connected mode exciters, and the
      measured performances are in good agreement with the numerical simulation results
      when taking into account the wall loss and assembly tolerance.

PMID- 28764508
TI  - Selective sensitivity in Kerr microscopy.
AB  - A new technique for contrast separation in wide-field magneto-optical Kerr
      microscopy is introduced. Utilizing the light from eight light emitting diodes,
      guided to the microscope by glass fibers and being switched synchronously with
      the camera exposure, domain images with orthogonal in-plane sensitivity can be
      displayed simultaneously at real-time, and images with pure in-plane or polar
      contrast can be obtained. The benefit of this new method of contrast separation
      is demonstrated for Permalloy films, a NdFeB sinter magnet, and a cobalt crystal.
      Moreover, the new technique is shown to strongly enhance the sensitivity of Kerr
      microscopy by eliminating parasitic contrast contributions occurring in
      conventional setups. A doubling of the in-plane domain contrast and a sensitivity
      to Kerr rotations as low as 0.6 mdeg is demonstrated.

PMID- 28764509
TI  - Note: Temperature effects in the modified Howland current source for electrical
      bioimpedance spectroscopy.
AB  - The aim of this study is to show how the modified Howland current source (MHCS)
      is affected by temperature changes. The source has been tested in a temperature
      range from 20 to 70  degrees C and frequency range from 100 Hz to 1 MHz.
      Parameters like output current, output impedance, total harmonic distortion, and
      oscillation have been measured. The measurements were made inside a temperature
      controlled environment. It was showed that the MHCS is stable at temperatures
      below 70  degrees C. Operational amplifiers with a low temperature drift and
      matching resistor should be carefully considered in order to prevent oscillations
      at high temperatures.

PMID- 28764510
TI  - Solid-state repetitive generator with a gyromagnetic nonlinear transmission line
      operating as a peak power amplifier.
AB  - In this work, experiments were made in which gyromagnetic nonlinear transmission
      line (NLTL) operates as a peak power amplifier of the input pulse. At such an
      operating regime, the duration of the input pulse is close to the period of
      generated oscillations, and the main part of the input pulse energy is
      transmitted only to the first peak of the oscillations. Power amplification is
      achieved due to the voltage amplitude of the first peak across the NLTL output
      exceeding the voltage amplitude of the input pulse. In the experiments, the input
      pulse with an amplitude of 500 kV and a half-height pulse duration of 7 ns is
      applied to the NLTL with a natural oscillation frequency of ~300 MHz. At the
      output of the NLTL in 40 Omega coaxial transmission line, the pulse amplitude is
      increased to 740 kV and the pulse duration is reduced to ~2 ns, which correspond
      to power amplification of the input pulse from ~6 to ~13 GW. As a source of input
      pulses, a solid-state semiconductor opening switch generator was used, which
      allowed carrying out experiments at pulse repetition frequency up to 1 kHz in the
      burst mode of operation.

PMID- 28764511
TI  - A small spacecraft for multipoint measurement of ionospheric plasma.
AB  - Measurement of ionospheric plasma is often performed by a single in situ device
      or remotely using cameras and radar. This article describes a small, low
      resource, deployed spacecraft used as part of a local, multipoint measurement
      network. A B-field aligned sounding rocket ejects four of these spin-stabilized
      spacecraft in a cross pattern. In this application, each spacecraft carries two
      retarding potential analyzers which are used to determine plasma density, flow,
      and ion temperature. An inertial measurement unit and a light-emitting diode
      array are used to determine the position and orientation of the devices after
      deployment. The design of this spacecraft is first described, and then results
      from a recent test flight are discussed. This flight demonstrated the successful
      operation of the deployment mechanism and telemetry systems, provided some
      preliminary plasma measurements in a simple mid-latitude environment, and
      revealed several design issues.

PMID- 28764512
TI  - Novel analysis technique for measuring edge density fluctuation profiles with
      reflectometry in the Large Helical Device.
AB  - A new method for measuring density fluctuation profiles near the edge of plasmas
      in the Large Helical Device (LHD) has been developed utilizing reflectometry
      combined with pellet-induced fast density scans. Reflectometer cutoff location
      was calculated by proportionally scaling the cutoff location calculated with fast
      far infrared laser interferometer (FIR) density profiles to match the slower time
      resolution results of the ray-tracing code LHD-GAUSS. Plasma velocity profile
      peaks generated with this reflectometer mapping were checked against velocity
      measurements made with charge exchange spectroscopy (CXS) and were found to agree
      within experimental uncertainty once diagnostic differences were accounted for.
      Measured density fluctuation profiles were found to peak strongly near the edge
      of the plasma, as is the case in most tokamaks. These measurements can be used in
      the future to inform inversion methods of phase contrast imaging (PCI)
      measurements. This result was confirmed with both a fixed frequency reflectometer
      and calibrated data from a multi-frequency comb reflectometer, and this method
      was applied successfully to a series of discharges. The full width at half
      maximum of the turbulence layer near the edge of the plasma was found to be only
      1.5-3 cm on a series of LHD discharges, less than 5% of the normalized minor
      radius.

PMID- 28764513
TI  - Note: Diagnostic deuterium beam with an ultra-small energy spread for plasma
      spectroscopy.
AB  - The DINA-5M diagnostic atomic beam has been upgraded to reduce the energy spread
      down to 50 eV. An active voltage stabilization system introduces a chain of
      varistors connected in series that can be switched with the time constant of 70
      MUs to minimize the deviation from the reference to the high-voltage level. Using
      deuterium, the enhanced diagnostic beam has the current of four atomic amperes
      and the energy of 50 keV +/- 50 eV. The primary considered application is a
      motional Stark effect diagnostic combined with laser-induced fluorescence, where
      the beam energy spread is an ultimate parameter determining the measurement
      performance.

PMID- 28764514
TI  - A small-volume PVTX system for broadband spectroscopic calibration of downhole
      optical sensors.
AB  - An instrument is presented that is capable of measuring the optical spectrum
      (long-wave ultraviolet through short-wave mid-infrared) of fluids under a range
      of temperature and pressure conditions from ambient pressure up to 138 MPa (20
      000 psi) and 422 K (300  degrees F) using ~5 ml of fluid. Temperature, pressure,
      and density are measured in situ in real-time, and composition is varied by
      adding volatile and nonvolatile components. The stability and accuracy of the
      conditions are reported for pure ethane, and the effects of temperature and
      pressure on characteristic regions of the optical spectrum of ethane are
      illustrated after correction for temperature and pressure effects on the optical
      cell path length, as well as normalization to the measured density. Molar
      absorption coefficients and integrated molar absorption coefficients for several
      vibrational combination bands are presented.

PMID- 28764515
TI  - Note: Lossless laser beam combiner employing a high-speed rotating half-wave
      plate.
AB  - We have developed a laser beam combiner employing a high-speed rotating half-wave
      plate based on the specific requirements of the Thomson scattering measurement
      systems in the ITER. The polarization extinction ratio of the output beam may
      exceed 1000 and was maintained for more than 1 h via feedback control of the half
      wave plate rotation speed. The pointing fluctuations introduced by rotating the
      half-wave plate were in the order of microradians. The high-speed rotating half
      wave plate provides a lossless means of combining laser beams together with
      stable beam pointing.

PMID- 28764516
TI  - Note: A wide temperature range MOKE system with annealing capability.
AB  - A novel sample stage integrated with a longitudinal MOKE system has been
      developed for wide temperature range measurements and annealing capabilities in
      the temperature range 65 K < T < 760 K. The sample stage incorporates a removable
      platen and copper block with inserted cartridge heater and two thermocouple
      sensors. It is supported and thermally coupled to a cold finger with two sapphire
      bars. The sapphire based thermal coupling enables the system to perform at higher
      temperatures without adversely affecting the cryostat and minimizes thermal drift
      in position. In this system the hysteresis loops of magnetic samples can be
      measured simultaneously while annealing the sample in a magnetic field.

PMID- 28764517
TI  - Quantifying non-contact tip-sample thermal exchange parameters for accurate
      scanning thermal microscopy with heated microprobes.
AB  - Simplified heat-transfer models are widely employed by heated probe scanning
      thermal microscopy techniques for determining thermal conductivity of test
      samples. These parameters have generally been assumed to be independent of sample
      properties; however, there has been little investigation of this assumption in
      non-contact mode, and the impact calibration procedures have on sample thermal
      conductivity results has not been explored. However, there has been little
      investigation of the commonly used assumption that thermal exchange parameters
      are sample independent in non-contact mode, or of the impact calibration
      procedures have on sample thermal conductivity results. This article establishes
      conditions under which quantitative, localized, non-contact measurements using
      scanning thermal microscopy with heated microprobes may be most accurately
      performed. The work employs a three-dimensional finite element (3DFE) model
      validated using experimental results and no fitting parameters, to determine the
      dependence of a heated microprobe thermal resistance as a function of sample
      thermal conductivity at several values of probe-to-sample clearance. The two
      unknown thermal exchange parameters were determined by fitting the 3DFE simulated
      probe thermal resistance with the predictions of a simplified probe heat transfer
      model, for two samples with different thermal conductivities. This calibration
      procedure known in experiments as the intersection method was simulated for
      sample thermal conductivities in the range of 0.1-50 W m-1 K-1 and clearance
      values in the 260-1010 nm range. For a typical Wollaston wire microprobe geometry
      as simulated here, both the thermal exchange radius and thermal contact
      resistance were found to increase with the sample thermal conductivity in the low
      thermal conductivity range while they remained approximately constant for thermal
      conductivities >1 W m-1 K-1, with similar trends reported for all clearance
      values investigated. It is shown that versatile sets of calibration samples for
      the intersection method should employ either medium range (1 W m-1 K-1) and (2 W
      m-1 K-1) thermal conductivities, or wide range (0.5 W m-1 K-1) and (50 W m-1 K
      1). The medium range yielded results within 1.5%-20.4% of the expected values of
      thermal conductivity for specimens with thermal conductivity within 0.1-10 W m-1
      K-1, while the wide range yielded values within 0.5%-19.4% in the same range.

PMID- 28764518
TI  - Absolute calibration of imaging plate detectors for electron kinetic energies
      between 150 keV and 1.75 MeV.
AB  - This paper presents the calibration of two different kinds of image plates (IPs)
      for detecting electrons with kinetic energy in the range of 150 keV-1.75 MeV. The
      calibration was performed using a 90Sr beta source. The paper also provides the
      measured fading response for the IPs in the time range from 12 min to 18 h.
      Calibration results are compared to Monte Carlo simulations of energy deposited
      by the electrons in the sensitive layer of the IPs. It was found that within this
      energy range a linear relation between simulated energy deposited by the electron
      in the phosphor layer and the measured photo stimulated luminescence in the IP is
      adequate to model the response of the IP.

PMID- 28764519
TI  - Stabilizing low-frequency oscillation with two-stage filter in Hall thrusters.
AB  - The use of a filter is the most common method to suppress low-frequency discharge
      current oscillation in Hall thrusters. The only form of filter in actual use
      involves RLC networks, which serve the purpose of reducing the level of conducted
      electromagnetic interference returning to the power processing unit, which is the
      function of a filter. Recently, the role of the filter in the oscillation control
      was introduced. It has been noted that the filter regulates the voltage across
      itself according to the variation of discharge current so as to decrease its
      fluctuation in the discharge circuit, which is the function of a controller.
      Therefore, a kind of two-stage filter is proposed to fulfill these two purposes,
      filtering and controlling, and the detailed design methods are discussed and
      verified. A current oscillation attenuation ratio of 10 was achieved by different
      capacitance and inductance combinations of the filter stage, and the standard
      deviation of low-frequency oscillations decreased from 3 A-1 A by the control
      stage in our experiment.

PMID- 28764520
TI  - Note: Electric field assisted megasonic atomization for size-controlled
      nanoparticles.
AB  - In this study, we report the use of megasonic atomization along with an electric
      field to reduce the aerosol particle size. The electric field assisted megasonic
      atomization (EMA) was achieved by implementing mesh and an induction charging
      ring at the output of a megasonic atomizer. The aim was to increase the number of
      particles generated and reduce the size of the particles to the nanoscale regime.
      In the present study, the megasonically generated NaCl and TiO2 aerosols were
      charged by applying an electric supply voltage up to +20 kV through the induction
      ring. The generated nanoparticles were evaluated by an electrical low-pressure
      impactor and scanning electron microscopy. It is observed that, for +15 kV, the
      number concentration of NaCl and TiO2 particles was found to have increased by up
      to five times, and the peak size of the particles was shifted from 40 nm to 15
      nm. The particle size reduction and increase in the number concentration might be
      due to Coulomb fission. Hence, the developed EMA system is suitable for many
      industrial applications where a large number of uniform-sized nanoparticles are
      required.

PMID- 28764521
TI  - A portable methane sampling system for radiocarbon-based bioportion measurements
      and environmental CH4 sourcing studies.
AB  - Radiocarbon measurements can be used to deduce the proportion of renewable to
      fossil carbon in materials. While these biofraction measurements are performed
      routinely on solid and liquid substances, measurements of gaseous samples, such
      as methane, are still scarce. As a pioneering effort, we have developed a field
      capable sampling system for the selective capture of CH4 for radiocarbon
      concentration measurements. The system allows for biofraction measurements of
      methane by accelerator mass spectrometry. In environmental research, radiocarbon
      measurements of methane can be used for fingerprinting different sources of
      methane emissions. In metrology and industry, biofraction measurements can be
      utilized to characterize biogas/natural gas mixtures within gas-line networks. In
      this work, the portable sampling system is described in detail and reference
      measurements of biofractions of gaseous fuel samples are presented. Low
      concentration (1-ppm-CH4) sampling for environmental applications appears
      feasible but has not been fully tested at present. This development allows for
      multitude of future applications ranging from Arctic methane emissions to biogas
      insertion to gas networks.

PMID- 28764522
TI  - Time-domain thermoreflectance (TDTR) measurements of anisotropic thermal
      conductivity using a variable spot size approach.
AB  - It is challenging to characterize thermal conductivity of materials with strong
      anisotropy. In this work, we extend the time-domain thermoreflectance (TDTR)
      method with a variable spot size approach to simultaneously measure the in-plane
      (Kr) and the through-plane (Kz) thermal conductivity of materials with strong
      anisotropy. We first determine Kz from the measurement using a larger spot size,
      when the heat flow is mainly one-dimensional along the through-plane direction,
      and the measured signals are only sensitive to Kz. We then extract the in-plane
      thermal conductivity Kr from a second measurement using the same modulation
      frequency but with a smaller spot size, when the heat flow becomes three
      dimensional, and the signal is sensitive to both Kr and Kz. By choosing the same
      modulation frequency for the two sets of measurements, we can avoid potential
      artifacts introduced by the frequency-dependent Kz, which we have found to be non
      negligible, especially for some two-dimensional layered materials like MoS2.
      After careful evaluation of the sensitivity of a series of hypothetical samples,
      we provided guidelines on choosing the most appropriate laser spot size and
      modulation frequency that yield the smallest uncertainty, and established a
      criterion for the range of thermal conductivity that can be measured reliably
      using our proposed variable spot size TDTR approach. We have demonstrated this
      variable spot size TDTR approach on samples with a wide range of in-plane thermal
      conductivity, including fused silica, rutile titania (TiO2 [001]), zinc oxide
      (ZnO [0001]), molybdenum disulfide (MoS2), hexagonal boron nitride (h-BN), and
      highly ordered pyrolytic graphite.

PMID- 28764523
TI  - Fabrication of large area flexible nanoplasmonic templates with flow coating.
AB  - We describe the development of a custom-built two-axis flow coater for the
      deposition of polymeric nanosphere monolayers that could be used in the
      fabrication of large area nanoplasmonic films. The technique described here has
      the capability of depositing large areas (up to 7 in. * 10 in.) of self-assembled
      monolayers of polymeric nanospheres onto polyethylene terephthalate (PET) films.
      Here, three sets of films consisting of different diameters (ranging from 100 to
      300 nm) of polymeric nanospheres were used to demonstrate the capabilities of
      this instrument. To improve the surface wettability of the PET substrates during
      wet-deposition, we enhanced the wettability by using a forced air blown-arc
      plasma treatment system. Both the local microstructure, as confirmed by scanning
      electron microscopy, describing monolayer and multilayer coverage, and the
      overall macroscopic uniformity of the resultant nanostructured film were
      optimized by controlling the relative stage to blade speed and nanosphere
      concentration. We also show using a smaller nanoparticle template that such
      monolayers can be used to form nanoplasmonic films. As this flow-coating approach
      is a scalable technique, large area films such as the ones described here have a
      variety of crucial emerging applications in areas such as energy, catalysis, and
      chemical sensing.

PMID- 28764524
TI  - Time-domain Brillouin scattering for the determination of laser-induced
      temperature gradients in liquids.
AB  - We present an optical technique based on ultrafast photoacoustics to determine
      the local temperature distribution profile in liquid samples in contact with a
      laser heated optical transducer. This ultrafast pump-probe experiment uses time
      domain Brillouin scattering (TDBS) to locally determine the light scattering
      frequency shift. As the temperature influences the Brillouin scattering
      frequency, the TDBS signal probes the local laser-induced temperature
      distribution in the liquid. We demonstrate the relevance and the sensitivity of
      this technique for the measurement of the absolute laser-induced temperature
      gradient of a glass forming liquid prototype, glycerol, at different laser pump
      powers-i.e., different steady state background temperatures. Complementarily, our
      experiments illustrate how this TDBS technique can be applied to measure thermal
      diffusion in complex multilayer systems in contact with a surrounding liquid.

PMID- 28764526
TI  - High-throughput heterodyne thermoreflectance: Application to thermal conductivity
      measurements of a Fe-Si-Ge thin film alloy library.
AB  - A High-Throughput Time-Domain ThermoReflectance (HT-TDTR) technique was developed
      to perform fast thermal conductivity measurements with minimum user actions
      required. This new setup is based on a heterodyne picosecond thermoreflectance
      system. The use of two different laser oscillators has been proven to reduce the
      acquisition time by two orders of magnitude and avoid the experimental artefacts
      usually induced by moving the elements present in TDTR systems. An amplitude
      modulation associated to a lock-in detection scheme is included to maintain a
      high sensitivity to thermal properties. We demonstrate the capabilities of the HT
      TDTR setup to perform high-throughput thermal analysis by mapping thermal
      conductivity and interface resistances of a ternary thin film silicide library
      FexSiyGe100-x-y (20<x,y<80) deposited by wedge-type multi-layer method on a 100
      mm diameter sapphire wafer offering more than 300 analysis areas of different
      ternary alloy compositions.

PMID- 28764527
TI  - An eight-channel Doppler backscattering system in the experimental advanced
      superconducting tokamak.
AB  - Doppler backscattering system can measure the perpendicular velocity and
      fluctuation amplitude of the density turbulence with intermediate wavenumber. An
      eight-channel Doppler backscattering system has been installed in the
      Experimental Advanced Superconducting Tokamak (EAST), which can probe eight
      different radial locations simultaneously by launching eight fixed frequencies
      (55, 57.5, 60, 62.5, 67.5, 70, 72.5, 75 GHz) into plasma. The quasi-optical
      system consists of circular corrugated waveguide transmission, a fixed parabolic
      mirror, and a rotatable parabolic mirror which are integrated with quasi-optics
      front-end of the profile reflectometer inside the vacuum vessel. The incidence
      angle can be chosen from 5 degrees  to 12 degrees , and the wavenumber range is 2
      15/cm with the wavenumber resolution Deltak/k<=0.21. Ray tracing simulations are
      used to calculate the scattering locations and the perpendicular wavenumber. The
      dynamic range of this new eight-channel Doppler backscattering system can be as
      large as 40 dB in the EAST. In this article, the hardware design, the ray
      tracing, and the preliminary experimental results in the EAST will be presented.

PMID- 28764528
TI  - Development of a high-speed vacuum ultraviolet (VUV) imaging system for the
      Experimental Advanced Superconducting Tokamak.
AB  - A high-speed vacuum ultraviolet (VUV) imaging system for edge plasma studies is
      being developed on the Experimental Advanced Superconducting Tokamak (EAST). Its
      key optics is composed of an inverse type of Schwarzschild telescope made of a
      set of Mo/Si multilayer mirrors, a micro-channel plate (MCP) equipped with a P47
      phosphor screen and a high-speed camera with CMOS sensors. In order to remove the
      contribution from low-energy photons, a Zr filter is installed in front of the
      MCP detector. With this optics, VUV photons with a wavelength of 13.5 nm, which
      mainly come from the line emission from intrinsic carbon (C vi: n = 4-2
      transition) or the Ly-alpha line emission from injected Li iii on the EAST, can
      be selectively measured two-dimensionally with both high temporal and spatial
      resolutions. At present, this system is installed to view the plasma from the low
      field side in a horizontal port in the EAST. It has been operated routinely
      during the 2016 EAST experiment campaign, and the first result is shown in this
      work. To roughly evaluate the system performance, synthetic images are created.
      And it indicates that this system mainly measures the edge localized emissions by
      comparing the synthetic images and experimental data.

PMID- 28764529
TI  - Manipulating motions of targeted single cells in solution by an integrated double
      ring magnetic tweezers imaging microscope.
AB  - Controlling and manipulating living cell motions in solution hold a high promise
      in developing new biotechnology and biological science. Here, we developed a
      magnetic tweezers device that employs a combination of two permanent magnets in
      up-down double-ring configuration axially fitting with a microscopic objective,
      allowing a picoNewton (pN) bidirectional force and motion control on the sample
      beyond a single upward pulling direction. The experimental force calibration and
      magnetic field simulation using finite element method magnetics demonstrate that
      the designed magnetic tweezers covers a linear-combined pN force with positive
      negative polarization changes in a tenability of sub-pN scale, which can be
      utilized to further achieve motion manipulation by shifting the force balance. We
      demonstrate an application of the up-down double-ring magnetic tweezers for
      single cell manipulation, showing that the cells with internalized paramagnetic
      beads can be selectively picked up and guided in a controlled fine motion.

PMID- 28764530
TI  - Oscillatory device for use with linear tribometer, for tribological evaluation of
      biomaterials.
AB  - Orthopedic implants still have limitations regarding their durability, despite
      being in use for over fifty years. Particles arising from wear due to the
      relative motion of their surfaces remain responsible for aseptic failure. This
      paper presents a device to be coupled with a reciprocal linear tribometer to
      reproduce the ex vivo wear of biomaterials, allowing the measurement of force and
      coefficient of friction. The device consists of a structure connected to the
      tribometer that transforms its reciprocal linear motion into one that is
      oscillatory for the mechanical assembly that contains the samples to test the
      desired biomaterials. The tribological pair used for testing consisted of Ultra
      High Molecular Weight Polyethylene (UHMWPE) in conjunction with the austenitic
      stainless steel AISI 316L in dry lubrication. The results showed that the values
      of the coefficient of friction in the linear mode and oscillatory mode and the
      UHMWPE life curve in the oscillatory mode were consistent with those cited in the
      literature for tests in a dry lubrication environment. Moreover, the UHMWPE
      sample life curve showed a reduction in the wear rate that can be explained by
      the preponderance of a wear mechanism over the others. The volumetric wear showed
      an increase with the number of cycles.

PMID- 28764532
TI  - Development of in situ two-coil mutual inductance technique in a multifunctional
      scanning tunneling microscope.
AB  - Superconducting thin films have been a focal point for intensive research efforts
      since their reduced dimension allows for a wide variety of quantum phenomena.
      Many of these films, fabricated in UHV chambers, are highly vulnerable to air
      exposure, making it difficult to measure intrinsic superconducting properties
      such as zero resistance and perfect diamagnetism with ex situ experimental
      techniques. Previously, we developed a multifunctional scanning tunneling
      microscope (MSTM) containing in situ four-point probe (4PP) electrical transport
      measurement capability in addition to the usual STM capabilities [Ge et al., Rev.
      Sci. Instrum. 86, 053903 (2015)]. Here we improve this MSTM via development of
      both transmission and reflection two-coil mutual inductance techniques for in
      situ measurement of the diamagnetic response of a superconductor. This addition
      does not alter the original STM and 4PP functions of the MSTM. We demonstrate the
      performance of the two-coil mutual inductance setup on a 10-nm-thick NbN thin
      film grown on a Nb-doped SrTiO3(111) substrate.

PMID- 28764533
TI  - Visualizing dispersive features in 2D image via minimum gradient method.
AB  - We developed a minimum gradient based method to track ridge features in a 2D
      image plot, which is a typical data representation in many momentum resolved
      spectroscopy experiments. Through both analytic formulation and numerical
      simulation, we compare this new method with existing DC (distribution curve)
      based and higher order derivative based analyses. We find that the new method has
      good noise resilience and enhanced contrast especially for weak intensity
      features and meanwhile preserves the quantitative local maxima information from
      the raw image. An algorithm is proposed to extract 1D ridge dispersion from the
      2D image plot, whose quantitative application to angle-resolved photoemission
      spectroscopy measurements on high temperature superconductors is demonstrated.

PMID- 28764534
TI  - Assessing infrared intensity using the evaporation rate of liquid hydrogen inside
      a cryogenic integrating sphere for laser fusion targets.
AB  - Infrared (IR) heating processes have been studied to form a deuterium layer in an
      inertial confinement fusion target. To understand the relationship between the IR
      intensity and the fuel layering time constant, we have developed a new method to
      assess the IR intensity during irradiation. In our method, a glass flask acting
      as a dummy target is filled with liquid hydrogen (LH2) and is then irradiated
      with 2-MUm light. The IR intensity is subsequently calculated from the time
      constant of the LH2 evaporation rate. Although LH2 evaporation is also caused by
      the heat inflow from the surroundings and by the background heat, the evaporation
      rate due to IR heating can be accurately determined by acquiring the time
      constant with and without irradiation. The experimentally measured IR intensity
      is 0.66 mW/cm2, which agrees well with a value estimated by considering the IR
      photon energy balance. Our results suggest that the present method can be used to
      measure the IR intensity inside a cryogenic system during IR irradiation of laser
      fusion targets.

PMID- 28764535
TI  - Note: A portable automatic capillary viscometer for transparent and opaque
      liquids.
AB  - A portable automatic capillary viscometer, equipped with an AVR microcontroller,
      was designed and developed. The viscometer was calibrated with Certified
      Reference Material (CRM) s200 and utilized for measurement of kinematic
      viscosity. A quadratic equation was developed for calibration of the instrument
      at various temperatures. Also, a model was developed for viscosity determination
      in terms of the viscometer dimensions. Development of the portable viscometer
      provides for on-site monitoring of engine oil viscosity.

PMID- 28764536
TI  - NanoRocks: Design and performance of an experiment studying planet formation on
      the International Space Station.
AB  - In an effort to better understand the early stages of planet formation, we have
      developed a 1.5U payload that flew on the International Space Station (ISS) in
      the NanoRacks NanoLab facility between September 2014 and March 2016. This
      payload, named NanoRocks, ran a particle collision experiment under long-term
      microgravity conditions. The objectives of the experiment were (a) to observe
      collisions between mm-sized particles at relative velocities of < 1 cm/s and (b)
      to study the formation and disruption of particle clusters for different particle
      types and collision velocities. Four types of particles were used: mm-sized
      acrylic, glass, and copper beads and 0.75 mm-sized JSC-1 lunar regolith simulant
      grains. The particles were placed in sample cells carved out of an aluminum tray.
      This tray was attached to one side of the payload casing with three springs.
      Every 60 s, the tray was agitated, and the resulting collisions between the
      particles in the sample cells were recorded by the experiment camera. During the
      18 months the payload stayed on ISS, we obtained 158 videos, thus recording a
      great number of collisions. The average particle velocities in the sample cells
      after each shaking event were around 1 cm/s. After shaking stopped, the inter
      particle collisions damped the particle kinetic energy in less than 20 s,
      reducing the average particle velocity to below 1 mm/s, and eventually slowing
      them to below our detection threshold. As the particle velocity decreased, we
      observed the transition from bouncing to sticking collisions. We recorded the
      formation of particle clusters at the end of each experiment run. This paper
      describes the design and performance of the NanoRocks ISS payload.

PMID- 28764537
TI  - A compact Class D RF power amplifier for mobile nuclear magnetic resonance
      systems.
AB  - A 20 MHz Class D amplifier with an output of 100 W of RF power has been
      developed. The compact size printed circuit board area of 50 cm2 and efficiency
      of 73% make it suitable for mobile nuclear magnetic resonance (NMR) systems. Test
      results show that the rise and ring down times of the amplifier are less than 0.2
      MUs, and it is capable of producing constant amplitude pulses as short as 2 MUs.
      Experiments using a Carr Purcell Meiboom Gill pulse sequence with a NMR MOUSE
      sensor confirm that the Class D amplifier is suitable for mobile NMR
      applications.

PMID- 28764538
TI  - A contactless positioning system for monitoring discontinuities in three
      dimensions with geological and geotechnical applications.
AB  - In this paper, a contactless positioning system is presented which has been
      designed to monitor the kinematic behavior of mechanical discontinuities in three
      dimensions. The positioning system comprises a neodymium magnet, fixed on one
      side of a discontinuity, and a magnetoresistive sensing array, fixed on the
      opposing side. Each of the anisotropic magnetoresistive sensors in the sensing
      array records the magnetic field along three orthogonal directions. The
      positioning system intrinsically generates compact data packages which are
      transmitted effectively using a range of standard wireless telecommunication
      technologies. These data are then modeled using a global least squares fitting
      procedure in which the adjustable parameters are represented by the position and
      orientation of the neodymium magnet. The instrumental resolution of the
      positioning system can be tuned depending on the strength of the magnetic field
      generated by the neodymium magnet and the distance between the neodymium magnet
      and the magnetoresistive sensing array. For a typical installation, the
      displacement resolution is shown to be circa 10 MUm while the rotation resolution
      is circa 0.1 degrees . The first permanently deployed positioning system was
      established in June 2016 to monitor the behavior of an N-S trending fault located
      at the contact between the eastern Alps and the Vienna Basin. The robust design
      of the positioning system is demonstrated by the fact that no interruptions in
      the broadcasted data streams have occurred since its installation. It has a range
      of potential applications in many areas of basic and applied research including
      geology, geotechnical engineering, and structural health monitoring.

PMID- 28764539
TI  - Magnetic induction of hyperthermia by a modified self-learning fuzzy temperature
      controller.
AB  - The aim of this study involved developing a temperature controller for magnetic
      induction hyperthermia (MIH). A closed-loop controller was applied to track a
      reference model to guarantee a desired temperature response. The MIH system
      generated an alternating magnetic field to heat a high magnetic permeability
      material. This wireless induction heating had few side effects when it was
      extensively applied to cancer treatment. The effects of hyperthermia strongly
      depend on the precise control of temperature. However, during the treatment
      process, the control performance is degraded due to severe perturbations and
      parameter variations. In this study, a modified self-learning fuzzy logic
      controller (SLFLC) with a gain tuning mechanism was implemented to obtain high
      control performance in a wide range of treatment situations. This implementation
      was performed by appropriately altering the output scaling factor of a fuzzy
      inverse model to adjust the control rules. In this study, the proposed SLFLC was
      compared to the classical self-tuning fuzzy logic controller and fuzzy model
      reference learning control. Additionally, the proposed SLFLC was verified by
      conducting in vitro experiments with porcine liver. The experimental results
      indicated that the proposed controller showed greater robustness and excellent
      adaptability with respect to the temperature control of the MIH system.

PMID- 28764540
TI  - Advances in liquid phase soft-x-ray photoemission spectroscopy: A new
      experimental setup at BESSY II.
AB  - A state-of-the-art experimental setup for soft X-ray photo- and Auger-electron
      spectroscopy from liquid phase has been built for operation at the synchrotron
      light facility BESSY II, Berlin. The experimental station is named SOL3, which is
      derived from solid, solution, and solar, and refers to the aim of studying solid
      liquid interfaces, optionally irradiated by photons in the solar spectrum. SOL3
      is equipped with a high-transmission hemispherical electron analyzer for
      detecting electrons emitted from small molecular aggregates, nanoparticles, or
      biochemical molecules and their components in (aqueous) solutions, either in
      vacuum or in an ambient pressure environment. In addition to conventional energy
      resolved electron detection, SOL3 enables detection of electron angular
      distributions by the combination of a +/-11 degrees  acceptance angle of the
      electron analyzer and a rotation of the analyzer in the polarization plane of the
      incoming synchrotron-light beam. The present manuscript describes the technical
      features of SOL3, and we also report the very first measurements of soft-X-ray
      photoemission spectra from a liquid microjet of neat liquid water and of TiO2
      nanoparticle aqueous solution obtained with this new setup, highlighting the
      necessity for state-of-the-art electron detection.

PMID- 28764542
TI  - Mini-beam modes on standard MX beamline BL17U at SSRF.
AB  - The macromolecular crystallography beamlines at third-generation synchrotron
      facilities play a central role in solving macromolecular crystal structures and
      also in understanding the biological function at molecular levels. The MX
      beamline BL17U at Shanghai Synchrotron Radiation Facility is a typical standard
      MX beamline with a focused beam size (H * V) of FWHM around 80 MUm * 45 MUm.
      However the protein samples brought to the beamline are down to 5-10 m from the
      important and challenging science project now. These samples require smaller size
      beam. In order to achieve the mini-size beamline, two mini-beam modes have been
      developed on BL17U: the pinhole-based mini-beam and the focused mini-beam by
      compound refractive lens (CRL). Compared to the pinhole-based mode, three times
      increase in flux is obtained by the CRL mode at a similar beam size. The flux
      gain obtained by the CRL needs to be considered for data collection strategies.
      It takes few minutes to switch the beamline from the normal to CRL mini-beam
      mode.

PMID- 28764541
TI  - A novel approach to estimating the Doppler shift frequency from quadrature mixer
      output.
AB  - Doppler backscattering systems (DBSs) have been widely used in magnetic
      confinement fusion devices to measure the density fluctuations and propagation
      velocity of turbulence. However, the received signals of a DBS usually include
      both zero-order reflection and backscattering components, which results in
      interference in calculating the Doppler shift frequency from the backscattering
      components. A novel method is introduced here for estimating the Doppler shift
      frequency by separating the zero-order reflection and backscattering components
      using the cross-phase spectrum between the I-signal and Q-signal from a
      quadrature mixer, based on the difference in symmetrical characteristics between
      the zero-order reflection and backscattering signal spectra. It is proven that
      this method is more effective than traditional approaches, such as multiple
      signal classification and fast Fourier transformation, for extracting Doppler
      shift information.

PMID- 28764543
TI  - Atomic layer deposition on porous powders with in situ gravimetric monitoring in
      a modular fixed bed reactor setup.
AB  - A modular setup for Atomic Layer Deposition (ALD) on high-surface powder
      substrates in fixed bed reactors with a gravimetric in situ monitoring was
      developed. The design and operation are described in detail. An integrated
      magnetically suspended balance records mass changes during ALD. The highly
      versatile setup consists of three modular main units: a dosing unit, a reactor
      unit, and a downstream unit. The reactor unit includes the balance, a large fixed
      bed reactor, and a quartz crystal microbalance. The dosing unit is equipped with
      a complex manifold to deliver gases and gaseous reagents including three
      different ALD precursors, five oxidizing or reducing agents, and two purge gas
      lines. The system employs reactor temperatures and pressures in the range of 25
      600  degrees C and 10-3 to 1 bar, respectively. Typically, powder batches between
      100 mg and 50 g can be coated. The capabilities of the setup are demonstrated by
      coating mesoporous SiO2 powder with a thin AlOx (submono) layer using three
      cycles with trimethylaluminium and H2O. The self-limiting nature of the
      deposition has been verified with the in situ gravimetric monitoring and full
      saturation curves are presented. The process parameters were used for a scale-up
      in a large fixed bed reactor. The samples were analyzed with established
      analytics such as X-ray diffraction, N2 adsorption, transmission electron
      microscopy, and inductively coupled plasma optical emission spectrometry.

PMID- 28764544
TI  - Pulsed high magnetic field measurement with a rubidium vapor sensor.
AB  - We present a new technique to measure pulsed magnetic fields based on the use of
      rubidium in gas phase as a metrological standard. We have therefore developed an
      instrument based on laser inducing transitions at about 780 nm (D2 line) in
      rubidium gas contained in a mini-cell of 3 mm * 3 mm cross section. To be able to
      insert such a cell in a standard high-field pulsed magnet, we have developed a
      fibred probe kept at a fixed temperature. Transition frequencies for both the pi
      (light polarization parallel to the magnetic field) and sigma (light polarization
      perpendicular to the magnetic field) configurations are measured by a commercial
      wavemeter. One innovation of our sensor is that in addition to the usual
      monitoring of the light transmitted by the Rb cell, we also monitor the
      fluorescence emission of the gas sample from a volume of 0.13 mm3. Our sensor has
      been tested up to about 58 T.

PMID- 28764545
TI  - Dynamic viscoelasticity measurement under alternative torque using
      electromagnetically spinning method with quadruple electromagnets.
AB  - In this study, we developed a novel type of rheological measurement system. Here,
      a spherical probe is driven to rotate periodically by applying torques using
      quadruple electromagnets in a noncontact manner. Moreover, this system is an
      enhancement of our electromagnetically spinning (EMS) viscometer, which is widely
      used for measuring rheological flow curves in various industrial fields. The
      quadruple EMS method provides the frequency spectrum of viscoelasticity, in
      addition to shear viscosity, in a steady flow by switching the operation modes of
      the driving torque. We show the results obtained for Newtonian fluids and
      viscoelastic materials and demonstrate the validity of the system.

PMID- 28764546
TI  - Double Hall sensor structure reducing voltage offset.
AB  - In this paper, we report on the double Hall sensor structure (DHSS) in which the
      voltage offset can be effectively reduced. The DHSS is composed of two standard
      Hall sensors that are activated with two currents from electrically independent
      current sources. The operation principle of the DHSS is explained in detail, and
      the concluded properties of the DHSS are confirmed in the experimental part of
      the paper. The measurements are performed on DHSSs based on InSb thin films. The
      offset is reduced by about three orders of magnitude. The minimum value of the
      reduced offset obtained is 10 MUV. It appears that the minimum reduced offset is
      limited by the electric noise. The advantage of DHSS is that it can be
      manufactured with the standard thin film technology enabling effective
      miniaturization of the system. The DHSS can effectively be used for the
      measurements of the Hall effect in ultra-thin layers containing the two
      dimensional electron gas, such as the epitaxial graphene.

PMID- 28764547
TI  - Extremely broadband single-shot cross-correlation frequency-resolved optical
      gating using a transient grating as gate and dispersive element.
AB  - A cross-correlation frequency-resolved optical gating (FROG) concept, potentially
      suitable for characterizing few or sub-cycle pulses in a single shot, is
      described in which a counter-propagating transient grating is used as both the
      gate and the dispersive element in a FROG spectrometer. An all-reflective setup,
      which can operate over the whole transmission range of the nonlinear medium,
      within the sensitivity range of the matrix sensor, is also proposed, and proof-of
      principle experiments for the ultraviolet and visible-to-near-infrared spectral
      ranges are reported.

PMID- 28764548
TI  - Cryopump development of the 5 MW neutral beam injector system on HL-2M tokamak.
AB  - In order to carry out the long pulse and high power neutral beam injector (NBI)
      heating experiment on the HL-2M tokamak and satisfy its high vacuum pumping speed
      in the NBI, two built-in cryopumps with large area and based on a three-stage
      adsorption structure have been developed. The design idea and size of the three
      stage structure, the manufacturing technique, and the test experiment for
      cryopumps have been described in this paper. The experimental result shows that
      the cooldown time of liquid nitrogen pipes and liquid helium pipes are 1.5 h and
      10 min, respectively. With activated charcoal bonded on the condensation plates,
      the pumping speed reaches 1.13 * 106 l/s, and the consumption of liquid helium is
      2.53 g/s and 3.11 g/s for the 4-component pump and the 5-component pump,
      respectively. The conductance probability of the pump inlet is 0.25 for hydrogen.

PMID- 28764549
TI  - Lightweight-compact variable-gap undulator with force cancellation system based
      on multipole monolithic magnets.
AB  - A lightweight-compact variable-gap undulator (LCVGU) having the force
      cancellation system based on the multipole monolithic magnets (MMMs) has been
      developed. The LCVGU is free from the heavy mechanical frames, which is a
      fundamental element specific to conventional variable-gap undulators (VGUs)
      because of a strong attractive force, and thus the cost and time for construction
      and installation are expected to be significantly reduced; the MMMs counteract
      the strong attractive force in a cost-effective manner. Results of mechanical
      tests and magnetic-field measurements of two prototype LCVGUs equipped with the
      proposed force cancellation system have revealed the comparable performance with
      the conventional VGUs.

PMID- 28764550
TI  - In situ multi-dimensional actuation measurement method for tensile actuation of
      paraffin-infiltrated multi-wall carbon nanotube yarns.
AB  - We introduce an experimental setup for the simultaneous measurement of axial and
      radial strain variations of a hybrid carbon nanotube (CNT) yarn actuator, where a
      paraffin wax is melt-infiltrated inside the CNT yarn. Such a hybrid yarn system
      has been known as a Joule-heating-driven tensile/torsional actuator due to a
      large volume expansion of the infiltrated paraffin upon a solid-to-liquid phase
      transition. During the operation of this actuator, however, the axial strain
      variations along the yarn axis and the diameter change of the yarn, which is the
      radial strain variations perpendicular to the yarn axis, had been measured
      separately, which prohibits the exact understanding of the whole actuation
      dynamics. In the new experimental configuration, a laser scan micrometer is
      employed for the in situ yarn's diameter measurement and is combined with the
      conventional tensile actuation measurement setup for real-time data-taking during
      the actuation. When the hybrid CNT yarn was tested, the synchronized strain
      variation data in the axial and radial directions were obtained, which helps the
      analysis of these actuation phenomena especially in the intermediate states.

PMID- 28764551
TI  - Linear servomotor probe drive system with real-time self-adaptive position
      control for the Alcator C-Mod tokamak.
AB  - A new servomotor drive system has been developed for the horizontal reciprocating
      probe on the Alcator C-Mod tokamak. Real-time measurements of plasma temperature
      and density-through use of a mirror Langmuir probe bias system-combined with a
      commercial linear servomotor and controller enable self-adaptive position
      control. Probe surface temperature and its rate of change are computed in real
      time and used to control probe insertion depth. It is found that a universal
      trigger threshold can be defined in terms of these two parameters; if the probe
      is triggered to retract when crossing the trigger threshold, it will reach the
      same ultimate surface temperature, independent of velocity, acceleration, or
      scrape-off layer heat flux scale length. In addition to controlling the probe
      motion, the controller is used to monitor and control all aspects of the
      integrated probe drive system.

PMID- 28764552
TI  - Extensions to the charge exchange recombination spectroscopy diagnostic suite at
      ASDEX Upgrade.
AB  - A new core charge exchange recombination spectroscopy diagnostic has been
      installed in the ASDEX Upgrade tokamak that is capable of measuring the impurity
      ion temperature, toroidal rotation, and density on both the low field side (LFS)
      and high field side (HFS) of the plasma. The new system features 48 lines-of
      sight (LOS) with a radial resolution that varies from +/-2 cm on the LFS down to
      +/-0.75 cm on the HFS and has sufficient signal to run routinely at 10 ms and for
      special circumstances down to 2.5 ms integration time. The LFS-HFS ion
      temperature profiles provide an additional constraint on the magnetic equilibrium
      reconstruction, and the toroidal rotation frequency profiles are of sufficiently
      high quality that information on the poloidal velocity can be extracted from the
      LFS-HFS asymmetry. The diagnostic LOS are coupled to two flexible-wavelength
      spectrometers such that complete LFS-HFS profiles from two separate impurities
      can be imaged simultaneously, albeit with reduced radial coverage. More
      frequently, the systems measure the same impurity providing very detailed
      information on the chosen species. Care has been taken to calibrate the systems
      as accurately as possible and to include in the data analysis any effects that
      could lead to spurious temperatures or rotations.

PMID- 28764553
TI  - Severe infections and subsequent delayed cardiovascular disease.
AB  - Background Severe infections in adulthood are associated with subsequent short
      term cardiovascular disease. Whether hospital admission for sepsis or pneumonia
      is associated with persistent increased risk (over a year after infection) is
      less well established. Design The design of this study was as a register-based
      cohort study. Methods Some 236,739 men born between 1952-1956 were followed from
      conscription assessments in adolescence to 2010. All-cause cardiovascular disease
      ( n = 46,754), including coronary heart disease ( n = 10,279) and stroke ( n =
      3438), was identified through national registers 1970-2010 (at ages 18-58 years).
      Results Sepsis or pneumonia in adulthood (resulting in hospital admission) are
      associated with increased risk of cardiovascular disease in the years following
      infection. The risk is highest during the first year after the infection, with an
      adjusted hazard ratio (and 95% confidence intervals) of 6.33 (5.65-7.09) and a
      notably increased risk persisted with hazard ratios of 2.47 (2.04-3.00) for the
      second and 2.12 (1.71-2.62) for the third year after infection. The risk
      attenuated with time, but remained raised for at least five years after
      infection; 1.87 (1.47-2.38). The results are adjusted for characteristics in
      childhood, cardiovascular risk factors and medical history in adolescence.
      Similar statistically significant associations were found for coronary heart
      disease and stroke. Conclusions Raised risks of cardiovascular disease following
      hospital admission for sepsis or pneumonia were increased for more than five
      years after the infection, but with the highest magnitude during the first three
      years following infection, suggesting a period of vulnerability when health
      professionals and patients should be aware of the heightened risk for
      cardiovascular disease.

PMID- 28764554
TI  - A new analog of pyrrolezanthine from the roots of Reynoutria ciliinervis (Nakai)
      Moldenke.
AB  - In the present study, a new analogue of pyrrolezanthine (1) was isolated from the
      roots of Reynoutria ciliinervis (Nakai) Moldenke. Its structure was elucidated
      mainly by NMR, HR-ESI-MS and the single-crystal X-ray diffraction spectroscopic
      data. Meanwhile, the antimicrobial activity of compound 1 was measured, it
      exhibited potent antifungal activity against Sclerotinia sclerotiorum with MIC
      value of 31.2 MUg/mL.

PMID- 28764556
TI  - Cumin scented leaf essential oil of Cinnamomum chemungianum: compositions and
      their in vitro antioxidant, alpha-amylase, alpha-glucosidase and lipase
      inhibitory activities.
AB  - As part of our work on prospecting of Cinnamomum of the Western Ghats, chemical
      compositions, antioxidant, alpha-amylase, alpha-glucosidase and lipase inhibitory
      activities of leaf essential oil (EO) of Cinnamomum chemungianum were evaluated.
      Chemical characterisation of the cumin scented leaf EO from five locations in the
      southern Western Ghats revealed that they were highly varied. EO from Kannikatti
      (CC2) exhibited good alpha-amylase inhibitory activity with IC50 value of 5.97
      MUg/mL, whereas the EOs from Chemungi (CC1) and Athirumala (CC5) showed better
      alpha-glucosidase inhibition with IC50 of 56.65 and 62.12 MUg/mL, respectively.
      The EOs from Chemungi, Kannikatti and Athirumala were found to inhibit lipase
      with IC50 of 919.75, 923.17 and 838.46 MUg/mL, respectively. The EO of C.
      chemungianum may be used in food products as it has cumin scent and mild
      inhibitory activities.

PMID- 28764557
TI  - Volatile and key odourant compounds of Turkish Berberis crataegina fruit using GC
      MS-Olfactometry.
AB  - This research was conducted to identify the aroma and aroma-active compounds of
      Berberis crataegina for the first time. Volatile profile of B. crataegina was
      obtained using the purge and trap extraction method with dichloromethane. Gas
      chromatography was coupled to mass spectrometry (GC-MS) allowed the quantitative
      and qualitative detection of 22 compounds in the sample. Aldehydes were the main
      chemical group in the sample and followed by aromatic alcohols and lactone. Aroma
      extract dilution analysis was implemented for the specification of key odourants
      of B. crataegina. In total, eight key odourants were detected in the extract of
      the sample, using GC-MS-Olfactometry and aldehydes were the leading chemical
      group. The key odourants, found to be contributing to the overall aroma in B.
      crataegina, were nonanal (FD = 1024; green, flowery), hexanal (FD = 512; green)
      and linalool (FD = 256; flowery, rose) because of high FD factors.

PMID- 28764555
TI  - Repeated measures dose-finding design with time-trend detection in the presence
      of correlated toxicity data.
AB  - BACKGROUND: Phase I trials are designed to determine the safety, tolerability,
      and recommended phase 2 dose of therapeutic agents for subsequent testing. The
      dose-finding paradigm has thus traditionally focused on identifying the maximum
      tolerable dose of an agent or combination therapy under the assumption that there
      is a non-decreasing relationship between dose-toxicity and dose-efficacy. The
      dose is typically determined based on the probability of severe toxicity observed
      during the first treatment cycle. A novel endpoint, the total toxicity profile,
      was previously developed to account for the multiple toxicity types and grades
      experienced in the first cycle. More recently, this was extended to a repeated
      measures design based on the total toxicity profile to account for longitudinal
      toxicities over multiple treatment cycles in the absence of within-patient
      correlation. METHODS: In this work, we propose to extend the design in the
      presence of within-patient correlation. Furthermore, we provide a framework to
      detect a toxicity time trend (toxicity increasing, decreasing, or stable) over
      multiple treatment cycles. We utilize a linear mixed model in the Bayesian
      framework, with the addition of Bayesian risk functions for decision-making in
      dose assignment. RESULTS: The performance of this design was evaluated using
      simulation studies and real data from a phase I trial. We demonstrated that using
      available toxicity data from all cycles of treatment improves the accuracy of
      maximum tolerated dose identification and allows for the detection of a time
      trend. The performance is consistent regardless of the strength of the within
      patient correlation. In addition, the use of a quasi-continuous total toxicity
      profile score significantly increased the power to detect time trends compared to
      when binary data only were used. CONCLUSION: The increased interest in
      molecularly targeted agents and immunotherapies in oncology necessitates
      innovative phase I study designs. Our proposed framework provides a tool to
      tackle some of the challenges presented by these novel agents, specifically
      through the ability to understand patterns of toxicity over time, which is
      important in the cases of cumulative or late toxicities.

PMID- 28764558
TI  - Commentary on Heath et al.

PMID- 28764559
TI  - Characterisation of phenolic compounds of the ethyl acetate fraction from
      Tabernaemontana catharinensis and its potential antidepressant-like effect.
AB  - This study evaluates the antidepressant-like effect and analysed the qualitative
      and quantitative 74 phenolic standards of ethyl acetate fraction from
      Tabernaemontana catharinensis leaves. Acute administration of fraction in mice
      reduced the immobility time in forced swimming and tail suspension tests
      confirming its antidepressant-like activity. The anti-immobility effect elicited
      by this fraction was prevented by the pretreatment of mice with PCPA (100 mg kg
      1), ketanserin (5 mg kg-1), SCH 23,390 (0.05 mg kg-1) or yohimbine (1 mg kg-1). A
      sub effective dose of the fraction produced a synergistic effect with fluoxetine
      (5 mg kg-1). Chromatographic analysis identified 4-hydroxybenzoic and p-coumaric
      acids in the ethyl acetate fraction from T. catharinensis. Capillary
      electrophoresis presented 7.34 +/- 0.02 mg g-1 of p-coumaric acid concentration
      in the fraction. Therefore, it is possible that antidepressant-like effect
      elicited by ethyl acetate fraction from T. catharinensis be dependent on the p
      coumaric acid.

PMID- 28764560
TI  - Serum collectrin levels in patients with early- and late-onset preeclampsia.
AB  - AIM: The aim of this study is to investigate the maternal levels of collectrin in
      early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE). To assess the
      correlation between serum collectrin levels and blood pressure in humans.
      MATERIAL AND METHODS: This cross-sectional study was conducted including 79
      pregnant women, 27 with normal pregnancy, 30 with EOPE and 22 with LOPE. Maternal
      serum levels of collectrin were measured by using enzyme-linked immunosorbent
      assay kits. RESULTS: The mean serum collectrin level was significantly lower in
      women with PE compared with the control group (8.49 +/- 3.12 ng/ml (EOPE), 9.69
      +/- 3.01 ng/ml (LOPE) versus 11.51 +/- 4.33 ng/ml) and was found to be the lowest
      in the EOPE group (8.49 +/- 3.12 ng/ml). The mean serum urea and uric acid levels
      were significantly higher in the PE group than the control group. Serum
      collectrin concentrations did not correlate with maternal age, BMI and serum
      creatinine levels. However, collectrin concentrations were negatively correlated
      with systolic blood pressure (r = -0.284, p = .011) and diastolic blood pressure
      (r = -0.275, p = .014) as well as with maternal serum urea (r = -0.269, p = .017)
      and uric acid (r = -0.219, p = .049) concentrations. CONCLUSION: Maternal serum
      collectrin levels are significantly lower in patients with preeclampsia than in
      the control group. There is an inverse correlation between serum collectrin
      levels and blood pressure.

PMID- 28764562
TI  - Does rapid HIV testing result in an early diagnosis and reduce the waiting time
      for patients to receive medical care?
AB  - The implementation of rapid HIV testing in Brazil began in 2006 for specific
      groups, and from 2009 was extended to the Counseling and Testing Centers (CTC) in
      certain Brazilian capitals. The aim of this study was to compare two groups of
      individuals: those diagnosed with HIV infection by conventional testing and those
      diagnosed with rapid testing, with respect to: the waiting time before receiving
      medical care, the time of the first laboratory tests and the virological, immune
      and clinical status. This is a cross-sectional study to compare a group with
      individuals diagnosed by conventional testing (2006-2008) and another with those
      diagnosed by rapid testing (2010-2011).The median time between blood collection
      and diagnosis of HIV in the conventional test group was 76 days, while in the
      rapid test group 94.2% of the subjects received their results on the same day of
      blood collection (p < 0.001). In the conventional test group, the median period
      of time before the first consultation with an infectious disease specialist was
      99 days, and for the rapid test group the time was 14 days (p < 0.001). The
      median time between the first blood sample and the first results of the CD4 count
      and viral load was approximately 2.5 times lower in the rapid test group (p <
      0.001 for both). The median CD4 count in the rapid test group (472) was higher
      than in the conventional test group (397) (p = 0.01). The introduction of rapid
      HIV testing as a diagnostic strategy has reduced the waiting times for medical
      care and laboratory tests and also allowed earlier diagnosis of HIV infection
      than with the conventional test.

PMID- 28764561
TI  - Canadian Guidelines for the Pharmacological Treatment of Schizophrenia Spectrum
      and Other Psychotic Disorders in Children and Youth.
AB  - OBJECTIVE: Schizophrenia spectrum and other psychotic disorders often have their
      onset in adolescence. The sequelae of these illnesses can negatively alter the
      trajectory of emotional, cognitive, and social development in children and youth
      if left untreated. Early and appropriate interventions can improve outcomes. This
      article aims to identify best practices in the pharmacotherapy management of
      children and youth with schizophrenia spectrum disorders. METHODS: A systematic
      search was conducted for published guidelines for schizophrenia and schizophrenia
      spectrum disorders in children and youth (under age 18 years). Recommendations
      were drawn from the National Institute for Health and Care Excellence guidelines
      on psychosis and schizophrenia in children and youth (2013 and 2015 updates).
      Current guidelines were adopted using the ADAPTE process, which includes
      consensus ratings by a panel of experts. RESULTS: Recommendations identified
      covered a range of issues in the pharmacotherapy management of children and youth
      with schizophrenia spectrum disorders. Further work in this area is warranted as
      we continue to further understand their presentation in the developing brain.
      CONCLUSIONS: Canadian guidelines for the pharmacotherapy management of children
      and youth with schizophrenia spectrum disorders are essential to assist
      clinicians in treating this vulnerable population. Ongoing work in this area is
      recommended.

PMID- 28764563
TI  - Patient profiles as organizing HIV clinicians' ART adherence management: a
      qualitative analysis.
AB  - The effectiveness of antiretroviral therapy (ART) depends on optimal clinical
      management and patient adherence. Little is known about patient characteristics
      that clinicians consider in the management of ART adherence. Exploring this
      issue, five focus groups were conducted with 31 HIV-clinicians from across
      France. A qualitative typological analysis suggests that clinician management of
      patient adherence is based on characteristics that coalesce into seven patient
      profiles. For the "passive" patient, described as taking ART exactly as
      prescribed without questioning their doctor's expertise, a directive and simple
      management style was preferred. The "misleading" patient is characterized as
      concerned with social desirability and as reporting no adherence difficulties for
      fear of displeasing their doctor. If clinical outcomes are suboptimal, the
      clinicians' strategy is to remind them of the importance of open patient
      clinician communication. The "stoic" patient is described as requesting and
      adequately taking the most potent ART available. Here, clinicians emphasize
      assessment of side effects, which the patient may minimize. The "hedonistic"
      patient's festive lifestyle and sexual risk-taking are seen as compromising
      adherence; with them, clinicians stress the patient's responsibility for their
      own health and that of their sexual partners. The "obsessive" patient is
      portrayed as having an irrational fear of ART failure and an inability to
      distinguish illusory from genuine adherence barriers. With this patient,
      clinicians seek to identify the latter. The "overburdened" patient is recognized
      as coping with life priorities that interfere with adherence and, with them, a
      forgiving ART is favored. The "underprivileged" patient is presented as having
      limited education, income and housing. In this case, clinicians seek to improve
      the patient's living conditions and access to care. These results shed light on
      HIV clinicians' ART adherence management. The value of these profiles for HIV
      care and patients should be investigated.

PMID- 28764564
TI  - Neonatal renal cystic diseases.
AB  - PURPOSE: Neonatal renal cystic diseases have a great impact on the morbidity and
      mortality of the affected neonates and infants. A good insight into the
      pathophysiology, diagnosis and treatment options of various neonatal renal cystic
      diseases aid in early diagnosis and intervention, thereby preventing
      complications. METHODS: PubMed search was done for articles on "neonatal renal
      cystic diseases" and relevant publications including reviews were considered for
      our article. RESULTS: Both hereditary and nonhereditary causes of cystic kidney
      diseases can result in severe morbidity and mortality. The main diagnostic
      modality is ultrasound imaging and most of the neonatal renal cystic diseases are
      detected during prenatal ultrasound screening. Commonly encountered neonatal
      renal cystic diseases are autosomal dominant polycystic kidney disease, autosomal
      recessive polycystic kidney disease and multicystic dysplastic kidney.
      CONCLUSIONS: A thorough knowledge of various renal cystic diseases can be of
      extreme prognostic value. Physicians should be aware of the impact of early
      diagnosis and intervention on the lives of those affected. Further research about
      treatment of these diseases is ongoing and can result in breakthrough therapies
      for these patients.

PMID- 28764565
TI  - Fluocinolone acetonide for the treatment of diabetic macular edema.
AB  - INTRODUCTION: Fluocinolone acetonide intravitreal implant is a non-erodible
      implant approved for the treatment of diabetic macular edema (DME) insufficiently
      responsive to available therapies. Areas covered: The injectable intravitreal
      implant releases fluocinolone acetonide at an average rate of 0.2 ug/day for at
      least 36 months. The two pooled pivotal FAME trials showed that, in patients with
      DME previously treated with laser photocoagulation, fluocinolone acetonide
      intravitreal implant was more beneficial than sham injection when looking at the
      proportion of patients with an improvement from baseline in visual acuity of more
      than 15 letters at 24 months and at 36 months. Cataract (82%) and intraocular
      pressure (IOP) elevation (37%) were the most common adverse events. Raised IOP
      was mostly treated with IOP-lowering medications, with <5% of eyes requiring
      incisional IOP-lowering surgery. FAME trial program results are confirmed by a
      series of real-world studies in eyes with chronic/recalcitrant DME. Expert
      opinion: data indicate that fluocinolone acetonide intravitreal implant is a
      useful second-line option for the treatment of DME.

PMID- 28764566
TI  - Practical insights on enzyme stabilization.
AB  - Enzymes are efficient catalysts designed by nature to work in physiological
      environments of living systems. The best operational conditions to access and
      convert substrates at the industrial level are different from nature and normally
      extreme. Strategies to isolate enzymes from extremophiles can redefine new
      operational conditions, however not always solving all industrial requirements.
      The stability of enzymes is therefore a key issue on the implementation of the
      catalysts in industrial processes which require the use of extreme environments
      that can undergo enzyme instability. Strategies for enzyme stabilization have
      been exhaustively reviewed, however they lack a practical approach. This review
      intends to compile and describe the most used approaches for enzyme stabilization
      highlighting case studies in a practical point of view.

PMID- 28764568
TI  - Thoracic aortic aneurysms: state of the art and current controversies.
AB  - INTRODUCTION: Complications of thoracic aortic aneurysms (TAA), including aortic
      rupture and dissection, are often catastrophic and prophylactic intervention can
      be lifesaving. Controversies exist regarding the standardization of aortic
      imaging techniques, the best metric for assessing aortic risk and the optimal
      threshold for intervention. Areas covered: This review summarizes recent temporal
      trends in TAA disease, provides an overview of the role of multi-modality imaging
      in diagnosis of the disease, and reviews controversies around surgical thresholds
      for intervention and medical therapies in the management of TAA disease. Expert
      commentary: While death from TAA appears to be declining, it remains an important
      cause of morbidity and mortality. Multi-modality imaging has revolutionized the
      diagnosis and follow up of TAAs but knowledge of the nuances of how images are
      acquired and measurements made are important. Emerging evidence suggests that the
      cross sectional area to height ratio may be a better measure of aortic risk,
      especially in those who do not meet current surgical thresholds. The use of
      medications to delay disease progression is controversial, but given the overall
      good safety profile of medications such as beta-blockers and angiotensin receptor
      blockers, they should be considered in all patients with TAA disease.

PMID- 28764567
TI  - Microalgae: a robust "green bio-bridge" between energy and environment.
AB  - Microalgae are a potential candidate for biofuel production and environmental
      treatment because of their specific characteristics (e.g. fast growth, carbon
      neutral, and rich lipid accumulations). However, several primary bottlenecks
      still exist in current technologies, including low biomass conversion efficiency,
      bio-invasion from the external environment, limited or costly nutrient sources,
      and high energy and capital input for harvest, and stalling its industrial
      progression. Coupling biofuel production with environmental treatment renders
      microalgae a more feasible feedstock. This review focuses on microalgae
      biotechnologies for both bioenergy generation and environmental treatment (e.g.
      CO2 sequestration and wastewater reclamation). Different intelligent technologies
      have been developed, especially during the last decade, to eliminate the
      bottlenecks, including mixotrophic/heterotrophic cultivation, immobilization, and
      co-cultivation. It has been realized that any single purpose for the cultivation
      of microalgae is not an economically feasible option. Combinations of
      applications in biorefineries are gradually reckoned to be necessary as it
      provides more economically feasible and environmentally sustainable operations.
      This presents microalgae as a special niche occupier linking the fields of energy
      and environmental sciences and technologies. The integrated application of
      microalgae is also proven by most of the life-cycle analysis studies. This study
      summarizes the latest development of primary microalgal biotechnologies in the
      two areas that will bring researchers a comprehensive view towards
      industrialization with an economic perspective.

PMID- 28764569
TI  - Screening for group B Streptococcus (GBS) at labour onset using PCR: accuracy and
      potential impact - a pilot study.
AB  - : This pilot study assessed the diagnostic accuracy and potential impact of a
      rapid PCR-based screening test for the detection of group B Streptococcus (GBS)
      at the onset of labour for the purpose of optimising intrapartum antibiotic
      prophylaxis (IAP). Vaginal and rectal swabs from a convenience sample of 158
      women were analysed by conventional broth-enriched culture and a rapid PCR test.
      Overall, GBS carriage was 18.98% by culture and 19.62% by PCR. PCR for the
      detection of GBS had a sensitivity of 93.1%, specificity of 96.67% and area under
      the curve (AUC) of 0.95. Only 19.3% GBS-positive women received IAP. Three
      fourths of babies born to GBS-positive mothers did not receive surveillance for
      early-onset GBS disease. Of the women who received IAP, only 32.5% were GBS
      carriers. Seventy-four percent of the GBS-positive mothers delivered more than 5
      h after recruitment, which gives adequate swab to delivery interval for
      appropriate antibiotic prophylaxis in labour. Impact statement What is already
      known about this subject: Appropriate intra-partum treatment of colonized mothers
      reduces the risk of GBS transmission to neonates. Universal ante partum screening
      of pregnant women or IAP based on risk factors in labour for GBS prevention fail
      to accurately identify and treat the woman who actually harbors GBS in the birth
      canal in labour. A PCR based rapid test, allows for real-time assessment of GBS
      carriage in labour. WHAT THIS STUDY ADDS: This study highlights the fact that a
      large number of GBS carriers in labour, who could potentially infect their
      babies, do not receive IAP, and most of their babies do not receive added
      surveillance in the neonatal period for EOGBS disease. It also confirms that PCR
      testing at onset of labour is a highly sensitive and reliable test that
      identifies the women who are GBS carriers in labour and hence need IAP. What the
      implications are of these findings for clinical practice and/or further research:
      Timely provision of IAP for the appropriate woman is possible by adopting
      universal GBS screening at the onset of labor using GBS-PCR. This would involve
      additional costs to health care facilities and added work to laboratory
      personnel.

PMID- 28764570
TI  - Short interpregnancy interval increases the risk of preterm premature rupture of
      membranes and early delivery.
AB  - OBJECTIVES: Preterm premature rupture of membranes (PPROM) is a major contributor
      to overall preterm birth (PTB) rates. A short interpregnancy interval (IPI) is a
      well-known risk factor for PTB. It is unknown if a short IPI specifically affects
      the risk of developing PPROM in a subsequent pregnancy. We sought to determine
      the association between IPI and the risk of PPROM in a subsequent pregnancy.
      METHODS: A retrospective cohort study using the Missouri birth certificate
      database of singleton births from 2003 to 2013 was conducted. A short IPI
      (delivery of the prior pregnancy to conception of the index pregnancy) was
      defined as <=6 months. IPI >6 months was categorized into two groups: IPI 7-23
      months and IPI >=24 months. PPROM was defined as premature rupture of membranes
      between 160 and 366 weeks. Multivariable logistic regression was conducted to
      determine the association between IPI and PPROM while controlling for maternal
      age, race, body mass index (BMI), education level, use of social services
      (Medicaid insurance, food stamps, or participation in the WIC [Women, Infants,
      and Children] program), tobacco use, and history of PTB. Secondary outcome
      included the gestational age at delivery, categorized into five subgroups (<=240,
      241-280, 281-320, 321-340, and 341-366 weeks). RESULTS: 474,957 subjects with
      singleton gestations had data available to calculate the IPI. Of these, 1.4% (n =
      6797) experienced PPROM. IPI <=6 months was significantly associated with an
      increased risk of developing PPROM compared with patients with IPI >=24 months
      (odds ratio (OR) 1.80, 95% CI 1.70-1.90, p < .001). A higher proportion of women
      with IPI <=6 months delivered between 281 and 320 weeks compared to the other two
      IPI groups (27.0 versus 15.0 and 16.4%, p < .001). Individual maternal factors
      associated with an increased risk of PPROM included advanced maternal age,
      African American race, BMI <18.5 kg/m2, BMI >=30 kg/m2, use of social services,
      tobacco use, and a prior PTB. CONCLUSION: Our data demonstrate that an IPI of <=6
      months is significantly associated with an increased risk of developing PPROM in
      the subsequent pregnancy. Of greater clinical relevance is that these women were
      more likely to deliver between 281 and 320 weeks as compared with women with a
      longer IPI. Novel to this study is the establishment of a specific link between a
      short IPI and PPROM with subsequent early delivery. Several maternal demographic
      factors known to be associated with PTB risk were also found to be associated
      with an increased risk of PPROM. Further studies are necessary to elucidate
      plausible biologic mechanisms ultimately leading to the development and
      implementation of preventive and therapeutic strategies for this high-risk
      cohort.

PMID- 28764571
TI  - Increased C4d and Bb immunoreactivity and decreased MBL immunoreactivity
      characterise first-time pathologic first-trimester miscarriage: a case-control
      study.
AB  - The role of the complement system in first-time pathologic first-trimester
      miscarriage was investigated. In this case-control study, tissue samples of 126
      women with pathologic miscarriage and termination of normal pregnancies were
      assessed. The pathologic pregnancy group consisted of 40 women with missed
      miscarriage, 13 women with incomplete miscarriage and 10 women with a blighted
      ovum. The control group consisted of 63 normal-appearing pregnancies.
      Immunoreactivity for C4d, Bb and MBL was evaluated in the deciduas and villous
      trophoblasts separately using a semi-quantitative histological scoring system (H
      score). C4d and Bb H-scores were higher and MBL H-score was reduced in the
      deciduas and villous tissues from pathologic miscarriage compared to termination
      of pregnancies (p = .003 and p = .001; p = .011 and p < .001; p < .001 and p <
      .001, respectively). C4d and Bb activities were increased and MBL activity was
      decreased in human first-time pathologic first-trimester miscarriage. We suggest
      that three complement pathways may play a role in human first-time pathologic
      first-trimester miscarriage. Impact statement Previous studies focussed on
      complement proteins related to a single complement pathway in cases often
      associated with antiphospholipid syndrome (APS) or recurrent miscarriage. In APS
      related cases, the classical pathway is activated. In antibody-dependent and in
      antibody-independent mouse models of foetal loss, classical and alternative
      pathways are activated, respectively. Lectin pathway deficiency has been reported
      in some recurrent miscarriage. The complement pathway or pathways, which have a
      role in human pathologic miscarriage was the starting point of this study. There
      has been no study done till now reporting the role of the three complement
      pathways in human pathologic miscarriage. In this study, we found increased
      classical and alternative complement pathway activities and decreased lectin
      pathway activity in tissues from first-time pathologic human miscarriage.

PMID- 28764572
TI  - Individualizing dual antiplatelet therapy duration after percutaneous coronary
      intervention: from randomized control trials to personalized medicine.
AB  - INTRODUCTION: Improved stent technologies have lead to reduced minimum durations
      of dual antiplatelet therapy (DAPT) to prevent stent thrombosis. However, the
      anti-ischemic benefits seen in extended DAPT in both stent and non-stent related
      lesions have called into question the optimum duration of DAPT after stent
      placement. Areas covered: We review the evidence for varying durations of DAPT
      after drug eluting stent placement including for patients on oral
      anticoagulation; decision tools available for clinicians to optimize patient
      selection for extended therapy and insight into application of these risk
      assessment tools in clinical practice. Expert commentary: The use of risk
      assessment tools in optimizing DAPT duration after stent placement provides an
      opportunity for improved outcomes by means of a personalized approach to care
      while allowing clinicians to engage with patients in shared-decision making.

PMID- 28764574
TI  - Designer drugs: Review and implications for emergency management.
AB  - In the past 10 years, "designer drugs" such as synthetic cannabinoids and
      cathinones have emerged and come into widespread use, resulting in more overdose
      cases involving these new drugs in the United States. Emergency departments
      regularly treat a diverse array of drug intoxications, and providers must be
      cognizant of novel drugs of abuse and the associated clinical presentations in
      order to provide the most appropriate care. This review aims to describe the
      epidemiology, mechanism of action, clinical presentation, and treatment of
      intoxication for both the common and newest drugs of abuse.

PMID- 28764573
TI  - Human periodontal ligament stem cells secretome from multiple sclerosis patients
      suppresses NALP3 inflammasome activation in experimental autoimmune
      encephalomyelitis.
AB  - Research in recent years has largely explored the immunomodulatory effects of
      mesenchymal stem cells (MSCs) and their secretory products, called "secretome,"
      in the treatment of neuroinflammatory diseases. Here, we examined whether such
      immunosuppressive effects might be elicited due to inflammasome inactivation. To
      this end, we treated experimental autoimmune encephalomyelitis (EAE) mice model
      of multiple sclerosis (MS) with the conditioned medium or purified
      exosomes/microvesicles (EMVs) obtained from relapsing-remitting-MS patients human
      periodontal ligament stem cells (hPDLSCs) and investigated the regulation of
      NALP3 inflammasome. We noticed enhanced expression of NALP3, Cleaved Caspase 1,
      interleukin (IL)-1beta, and IL-18 in EAE mouse spinal cord. Conversely, hPDLSCs
      conditioned medium and EMVs significantly blocked NALP3 inflammasome activation
      and provided protection from EAE. Reduction in NALP3, Cleaved Caspase 1, IL
      1beta, and IL-18 level was noticed in conditioned medium and EMVs-treated EAE
      mice. Pro-inflammatory Toll-like receptor (TLR)-4 and nuclear factor (NF)-kappaB
      were elevated in EAE, while hPDLSCs-conditioned medium and EMVs treatment reduced
      their expression and increased IkappaB-alpha expression. Characterization of
      hPDLSCs-conditioned medium showed substantial level of anti-inflammatory IL-10,
      transforming growth factor (TGF)-beta, and stromal cell-derived factor 1alpha
      (SDF-1alpha). We propose that the immunosuppressive role of hPDLSCs-derived
      conditioned medium and EMVs in EAE mice may partly attribute to the presence of
      soluble immunomodulatory factors, NALP3 inflammasome inactivation, and NF-kappaB
      reduction.

PMID- 28764575
TI  - An overview on biodegradation of polystyrene and modified polystyrene: the
      microbial approach.
AB  - Polystyrene is a widely used plastic in many aspects of human life and in
      industries due to its useful characteristics of low cost, light weight, ease of
      manufacture, versatility, thermal efficiency, durability, and moisture
      resistance. However, polystyrene is very stable and extremely hard to degrade in
      the environment after disposal. Polystyrene can be used as a carbon source for
      microorganisms similar to many other hydrocarbons. The ability of microorganisms
      to use polystyrene as a carbon source has been recently established. However, the
      high molecular weight of polystyrene limits its use as a substrate for enzymatic
      reactions to take place. In this paper, we review studies on biodegradation of
      polystyrene to give an overview and direction for future studies.

PMID- 28764576
TI  - Contemporary evaluation of mitral regurgitation - 3D echocardiography, cardiac
      magnetic resonance, and procedural planning.
AB  - INTRODUCTION: Mitral regurgitation is one of the more common forms of valvular
      heart disease. Given the expansion of therapies for structural heart disease, new
      therapies for mitral regurgitation are emerging. An accurate description and
      classification of mitral disease is important to understand pathology and provide
      recommendations for therapy. Areas covered: In the modern evaluation of mitral
      regurgitation, 3-dimensional echocardiography (3DE) and cardiac magnetic
      resonance imaging (CMR) play important roles which overcome the prior limitations
      of 2-dimensional echocardiography. Specifically, an advanced evaluation with
      these techniques allows accurate characterization of the anatomic etiology of
      mitral regurgitation and quantification of severity. Furthermore, the role of 3DE
      during intraprocedural guidance, 'interventional echocardiography,' is expanding.
      Expert commentary: In our review, we demonstrate a complete diagnostic evaluation
      of mitral valve dysfunction by 3DE and CMR and describe current implications for
      invasive therapy and procedural guidance.

PMID- 28764577
TI  - MELK: a potential novel therapeutic target for TNBC and other aggressive
      malignancies.
AB  - INTRODUCTION: There is an unmet need in triple-negative breast cancer (TNBC)
      patients for targeted therapies. Maternal embryonic leucine zipper kinase (MELK)
      is a promising target for inhibition based on the abundance of correlative and
      functional data supporting its role in various cancer types. Areas covered: This
      review endeavors to outline the role of MELK in cancer. Studies covering a range
      of biological functions including proliferation, apoptosis, cancer stem cell
      phenotypes, epithelial-to-mesenchymal transition, metastasis, and therapy
      resistance are discussed here in order to understand the potential of MELK as a
      clinically significant target for TNBC patients. Expert opinion: Targeting MELK
      may offer a novel therapeutic opportunity in TNBC and other cancers. Despite the
      abundance of correlative data, there is still much we do not know. There are a
      lack of potent, specific inhibitors against MELK, as well as an insufficient
      understanding of MELK's downstream substrates. Addressing these issues is the
      first step toward identifying a patient population that could benefit from MELK
      inhibition in combination with other therapies.

PMID- 28764578
TI  - Developments in early diagnosis and therapy of HIV infection in newborns.
AB  - INTRODUCTION: Infants who acquire HIV have an exceptionally high risk of
      morbidity and mortality if they do not receive antiretroviral therapy (ART).
      Areas covered: This review aims to summarize the currently available evidence on
      ART in HIV-infected neonates. Data were obtained from literature searches from
      PubMed, abstracts from International Conferences (2000-2017), and authors' files.
      Expert opinion: Current evidence favors early diagnosis and prompt ART of HIV
      infection in newborns. The precise timing of initiation of ART remains
      undetermined. Very early (close to birth) ART appears to limit the size of the
      viral reservoir and may restrict replication-competent virus, but the clinical
      benefit remains unproven. Among the current options for initial therapy, in full
      term neonates from 2 weeks of life onwards, a lopinavir/ritonavir-based three
      drug regimen is preferred. In term infants, younger than 2 weeks a nevirapine
      based regimen is recommended, although there are no clinical trial data
      supporting that initiating treatment before 2 weeks improves outcome compared to
      starting afterwards. Existing safety information is insufficient to recommend ART
      in preterm infants, with pharmacokinetic data available for zidovudine only. If
      ART is considered in this setting, an individual case assessment of the
      risk/benefit ratio of treatment should be made.

PMID- 28764579
TI  - Foley catheter versus intravaginal prostaglandins E2 for cervical ripening in
      women at term with an unfavorable cervix: a randomized controlled trial.
AB  - OBJECTIVE: The objective of this study is to compare the efficacy of labor
      induction by Foley catheter balloon (FCB) insertion to intravaginal dinoprostone
      tablet placement in women with an unfavorable cervix. MATERIALS AND METHODS: A
      prospective randomized controlled trial was conducted. Women were assigned to
      insertion of a FCB or placement of a vaginal dinoprostone tablets and their
      outcome were compared. RESULTS: The study comprised 300 women. The time to active
      labor was significantly shorter in the FCB compared with the dinoprostone group,
      but required more oxytocin administration. A lower rate of cesarean section was
      found only in nulliparous women in the FCB group. The neonatal outcome was
      favorable and similar in both groups. CONCLUSION: Both methods had similar
      results regarding achieving vaginal delivery within 24 h and cesarean section
      rate. For nulliparous women, the FCB induction method had the advantage of a
      shorter time to active labor and a lower rate of cesarean section.

PMID- 28764580
TI  - Cue Competition Influences Biconditional Discrimination.
AB  - When multiple cues are presented in compound and trained to predict an outcome,
      the cues may compete for association with an outcome. However, if both cues are
      necessary for solution of the discrimination then competition might be expected
      to interfere with solution of the discrimination. We consider how unequal
      stimulus salience influences learning in configural discriminations, where no
      individual stimulus predicts the outcome. We compared two hypotheses; (1)
      salience modulation minimises the initial imbalance in salience and (2) that
      unequal stimulus salience will impair acquisition of configural discriminations.
      We assessed the effect of varying stimulus salience in a biconditional
      discrimination (AX+, AY-, BX-, BY+). Across two experiments, we found stronger
      discrimination when stimuli had matched, rather than mismatched, salience,
      supporting our second hypothesis. We discuss the implications of this finding for
      Mackintosh's (1975) model of selective attention, modified elemental models
      (e.g., McLaren & Mackintosh, 2002) and configural models of learning.

PMID- 28764581
TI  - Skin diseases of the vulva: inflammatory, erosive-ulcerating and apocrine gland
      diseases, zinc and vitamin deficiency, vulvodynia and vestibulodynia.
AB  - Chronic, inflammatory and ulcerating mucocutaneous diseases that can affect the
      vulvar area are reviewed: lichen sclerosus, lichen planus, plasma cell vulvitis,
      complex aphthosis, Behcet's disease, pyoderma gangrenosum, metastatic Crohn's
      disease, dyskeratotic skin diseases (Hailey-Hailey disease and Darier's disease),
      autoimmune bullous diseases (mucous membrane pemphigoid and pemphigus vulgaris)
      and hidradenitis suppurativa. Also, vulvodynia and vestibulodynia, zinc and
      vitamin B deficiency are described.

PMID- 28764582
TI  - How Drone Strikes and a Fake Vaccination Program Have Inhibited Polio Eradication
      in Pakistan: An Analysis of National Level Data.
AB  - This article investigates whether the United States' counterinsurgency operations
      have inhibited polio eradication efforts in northwestern Pakistan, the world's
      last major reservoir of polio. Anecdotal evidence suggests that militants disrupt
      polio vaccination programs because of suspicions that campaigns are a cover for
      gathering intelligence on Central Intelligence Agency (CIA) drone targets. This
      paper analyzes national-level quantitative data to test this argument. Between
      2004 and 2012, the number of polio cases in Pakistan closely mirrored the number
      of drone strikes. But from 2013 onward, polio cases increased while drone strikes
      fell. This can be explained by the CIA's use of a fake immunization campaign in a
      failed attempt to obtain the DNA of Osama bin Laden's relatives prior to his
      assassination in 2011. This seemingly vindicated militants' suspicions that
      vaccination programs were a cover for espionage. Militants consequently
      intensified their disruption of immunization campaigns, resulting in an increase
      in polio cases in Pakistan, as well as in Afghanistan, Syria, and Iraq. For
      politicians and military planners, drones are attractive because they are said to
      harm fewer civilians than conventional methods of warfare. However, this paper
      demonstrates that drone strikes had negative effects on the well-being of
      civilians in Pakistan and further afield because they undermined global efforts
      to eradicate polio.

PMID- 28764583
TI  - Expression and significance of aquaporin-2 and serum hormones in placenta of
      patients with preeclampsia.
AB  - To evaluate the relationship between serum hormone or aquaporin-2 (AQP-2) and
      preeclampsia, patients with severe preeclampsia (A group), mild preeclampsia (B
      group), chronic hypertension (C group) and normal pregnant women (D group) were
      recruited and analysed. The AQP-2 level in placenta tissues was detected and the
      correlations of AQP-2 with serum hormone levels were analysed using linear
      correlation regression analysis. The differences of alpha foetal protein (AFP)
      and human chorionic gonadotropin (HCG) levels during mid-pregnancy, as well as
      the levels of AFP, HCG, unconjugated oestriol and progesterone during late
      pregnancy were significant among A, B, C and D groups (p < .05). The AQP-2 level
      in placenta tissues was higher in A group than that in other groups (p < .05).
      The AQP-2 was correlated with HCG (p < .05). In conclusion, AQP-2 may be involved
      in the development of severe preeclampsia, which may be related to serum HCG.

PMID- 28764584
TI  - Sonographic correlation of foetal neck circumference and area with gestational
      age among pregnant women in Port Harcourt, Nigeria.
AB  - The purpose of this study was to create a reference range nomogram of foetal neck
      circumference (FNC) and foetal neck area (FNA) in a Nigerian population using
      polynomial regression models. This cross-sectional study involved 723 pregnant
      women between 14 and 40 weeks of gestation. Axial measurements of the FNC and FNA
      were obtained in three measurements and the mean taken as the final value and the
      5th, 50th and 95th percentiles for each foetal gestational age (FGA) were
      calculated. FNC and FNA correlated strongly with FGA, biparietal diameter,
      abdominal circumference, head circumference, and femoral length. Cubic models
      fitted the FNC vs FGA, and FNA vs. FGA values, and the mathematical relationships
      are given as: [Formula: see text] [Formula: see text] [Formula: see text].
      Nomograms of FNC and FNA are thus generated. Impact statement The foetal neck
      circumference (FNC) and foetal neck area (FNA) can serve as predictors of foetal
      gestational age (FGA) since they correlate strongly and positively with FGA and
      known biometric parameters. The measurements obtained vary with the population
      studied. This study provides a nomogram of the FNA and FNC for an African
      population. The values correlate with that of the Caucasian population up to 32
      weeks FGA. Interestingly, FNA and FNC measurements demonstrate high correlation
      but poor agreement in measurements between sonographers. Even though FNA and FNC
      could be used as predictors of foetal gestational age, the measurements vary
      significantly between sonographers. This is attributable to the difficulty in
      obtaining a satisfactory axial view of foetal neck, which is dependent on foetal
      presentation.

PMID- 28764585
TI  - Sexual transactions between long distance truck drivers and female sex workers in
      South Africa.
AB  - BACKGROUND: Female sex workers (FSWs) and long distance truck drivers (LDTDs) are
      considered key populations at high risk for HIV transmission due to high
      prevalence. The intersection of these mobile populations presents unique
      challenges in the fight against HIV and the movement towards reducing new
      infections. OBJECTIVE: The purpose of this study was to explore the nature of sex
      trade along a particular transport route. Sexual transactions and the
      vulnerabilities that exist between these two groups with regards to HIV/AIDS are
      described, with the purpose of furthering the agenda for targeted interventions.
      METHODS: Qualitative in-depth interviews were conducted with 14 participants,
      seven FSWs and seven LDTDs. We recruited FSWs through snowballing, and LDTDs
      through intercepts at truck stops. Semi-structured interview guides were used for
      data collection, and thematic analysis was conducted. RESULTS: The sex trade in
      this study is characterized by competition, fuelled by money-driven and age
      disparate rivalry. Despite widespread HIV knowledge, FSWs contend with persistent
      challenges regarding condom use negotiation, induced by more money in the
      exchange for unsafe sex. Despite the placement of wellness centres in truck stops
      along the highway, LDTDs face stigma related challenges with regards to testing
      for HIV and personal acknowledgement of their involvement in the sex trade.
      CONCLUSION: The nature of the sex trade along the highway continues to be risky
      despite the availability of HIV testing and antiretroviral treatment (ART). The
      sex trade is perceived to be increasing along trucking routes, in spite of
      measures instituted to limit access to FSWs. FSWs struggle to cope with the
      pressure of unprotected sex because of the need to generate more income, as well
      as avoid incidents of violence and threats. Interventions along transport routes
      need to be inclusive of FSWs who could play a vital role in stigma reduction
      amongst LDTDs through peer education.

PMID- 28764586
TI  - Retrospective analysis of 4761 cases who underwent amniocentesis in southeast
      China.
AB  - The aim of this study was to examine the clinical and cytogenetic results of 4761
      amniocentesis (AS) cases retrospectively in our clinic in southeast China. The
      prenatal diagnosis indications, detected chromosomal anomalies and the detection
      rate of chromosomal abnormalities were studied in 4761 patients who underwent AS
      between June 2014 and July 2016 retrospectively. Chromosomal abnormality was
      detected in 137 (2.88%) of the 4761 samples (89.1% numerical, 10.9% structural).
      The most frequent numerical chromosomal abnormality was trisomy 21 (59.0%).
      Clinically insignificant polymorphisms were the most frequent structural changes
      (n = 284). In our study, the frequency and proportion of abnormal karyotypes
      varied substantially across different maternal AS indications. Impact statement
      What is already known on this subject: Several studies on amniocentesis
      indications and results have been reported from China and from other countries.
      It has been known that the most common indications were the increased risk at
      maternal serum screenings (MSS) and advanced maternal age (AMA). What the results
      of this study add: In our study we make a conclusion that the indications and
      results of AS cases from our centre indicated the significance of genetic
      screening. What the implications are of these findings for clinical practice
      and/or further research: Our data could offer informative data for proper
      prenatal genetic counselling of pregnant women and their partners in Wuxi, China.

PMID- 28764587
TI  - Corrigendum.

PMID- 28764588
TI  - N1, N14-diferuloylspermine as an antioxidative phytochemical contained in leaves
      of Cardamine fauriei.
AB  - Most Brassicaceae vegetables are ideal dietary sources of antioxidants beneficial
      for human health. Cardamine fauriei (Ezo-wasabi in Japanese) is a wild, edible
      Brassicaceae herb native to Hokkaido, Japan. To clarify the main antioxidative
      phytochemical, an 80% methanol extraction from the leaves was fractionated with
      Diaion(r) HP-20, Sephadex(r) LH-20, and Sep-Pak(r) C18 cartridges, and the
      fraction with strong antioxidant activity depending on DPPH method was purified
      by HPLC. Based on the analyses using HRESIMS and MS/MS, the compound might be N1,
      N14-diferuloylspermine. This rare phenol compound was chemically synthesized,
      whose data on HPLC, MS and 1H NMR were compared with those of naturally derived
      compound from C. fauriei. All results indicated they were the same compound. The
      radical-scavenging properties of diferuloylspermine were evaluated by ORAC and
      ESR spin trapping methods, with the diferuloylspermine showing high scavenging
      activities of the ROO., O2.-, and HO. radicals as was those of conventional
      antioxidants.

PMID- 28764590
TI  - Vasculitis causing massive infarction: a rare presentation of primary cerebral
      phaeohyphomycosis.

PMID- 28764589
TI  - Uncovering How Urban Regeneration Programs May Stimulate Leisure-time Walking
      Among Adults in Deprived Areas: A Realist Review.
AB  - Evidence suggests that urban regeneration programs can stimulate leisure-time
      walking (LTW) in deprived areas. However, underlying pathways remain unclear.
      This study explored how urban regeneration might stimulate LTW among adults in
      deprived areas. We conducted a realist review, a theory-driven approach to
      evidence synthesis that focuses on mechanisms. We searched three electronic
      databases for peer-reviewed literature that describes how the neighborhood
      environment or urban regeneration influences LTW among adults in deprived areas.
      Evidence from 13 qualitative studies was synthesized. All studies indicated that
      safety problems and poor physical neighborhood design make adults fearful of
      walking. Seven studies indicated that poor aesthetics makes walking less relaxing
      and stress releasing. Seven studies indicated that poor infrastructure makes it
      inconvenient for adults to walk. A limited number of studies indicated that a
      lack of LTW facilities creates a shortage of settings for walking and that low
      levels of social capital constrain social support for walking and social
      interaction while walking. Evidence from this study suggests that urban
      regeneration might stimulate LTW among adults in deprived areas by creating a
      neighborhood that is less frightening, more relaxing, and more convenient to walk
      in.

PMID- 28764592
TI  - Rifampicin-induced immune allergic reaction.

PMID- 28764591
TI  - Segmental colectomy for bleeding diverticular disease guided by the PEEP test.
AB  - Many patients with massive lower gastrointestinal (GI) haemorrhage from
      diverticulosis are subjected to total colectomy when preoperative localisation is
      unavailable. We dissected colectomy specimens and noted that there was limited
      retrograde reflux in most of these cases. Therefore, we sought to assess the
      value of a positive endoluminal erythrocyte presence (PEEP) test (presence of
      fresh blood in the caecum) to direct segmental colectomies in 14 patients who
      required emergency operations for massive lower GI haemorrhage. Overall, 13 (93%)
      patients who had segmental colectomy guided by the PEEP test had successful
      control of bleeding. There was no mortality and a 14% postoperative morbidity
      after segmental resections guided by the PEEP test. One patient had persistent
      bleeding and required a completion colectomy on the third postoperative day. We
      propose that the PEEP test be added to the surgical armamentarium to guide
      segmental resection in the absence of localisation by conventional means.
      However, we advocate blind total colectomy if the PEEP test is equivocal and
      early completion colectomy if there is significant re-bleeding.

PMID- 28764593
TI  - Right-ear precedence and vocal emotion contagion: The role of the left
      hemisphere.
AB  - Much evidence suggests that the processing of emotions is lateralized to the
      right hemisphere of the brain. However, under some circumstances the left
      hemisphere might play a role, particularly for positive emotions and emotional
      experiences. We explored whether emotion contagion was right-lateralized,
      lateralized valence-specifically, or potentially left-lateralized. In two
      experiments, right-handed female listeners rated to what extent emotionally
      intoned pseudo-sentences evoked target emotions in them. These sound stimuli had
      a 7 ms ear lead in the left or right channel, leading to stronger stimulation of
      the contralateral hemisphere. In both experiments, the results revealed that
      right ear lead stimuli received subtly but significantly higher evocation scores,
      suggesting a left hemisphere dominance for emotion contagion. A control
      experiment using an emotion identification task showed no effect of ear lead. The
      findings are discussed in relation to prior findings that have linked the
      processing of emotional prosody to left-hemisphere brain regions that regulate
      emotions, control orofacial musculature, are involved in affective empathy
      processing areas, or have an affinity for processing emotions socially. Future
      work is needed to eliminate alternative interpretations and understand the
      mechanisms involved. Our novel binaural asynchrony method may be useful in future
      work in auditory laterality.

PMID- 28764594
TI  - Intraoperative endoscopic ultrasound guidance for laparoscopic excision of
      invisible symptomatic deep intramural myomas.
AB  - The aim of this study was to evaluate the feasibility of intraoperative
      endoscopic ultrasound guidance for excision of symptomatic deep intramural myomas
      that are not otherwise visible at laparoscopy. Seventeen patients with
      symptomatic deep intramural myomas who underwent laparoscopic myomectomy with
      intraoperative endoscopic ultrasound guidance were followed up and reported. All
      myomas were removed successfully. The endometrium was breached in one patient.
      All patients were relieved of their symptoms and three patients presenting with
      infertility conceived. There were no short- or long-term complications associated
      with the procedure. One patient who had multiple myomas necessitated intravenous
      iron treatment prior to discharge. Laparoscopic removal of small symptomatic deep
      intramural myomas is facilitated by the use of intraoperative endoscopic
      ultrasound that enables exact localisation and correct placement of the serosal
      incision. Impact statement What is already known on this subject: When the myoma
      is symptomatic, compressing the endometrium, does not show serosal protrusion and
      is not amenable to hysteroscopic resection, laparoscopic surgery may become
      challenging. What do the results of this study add: The use of intraoperative
      endoscopic ultrasound under these circumstances may facilitate the procedure by
      accurate identification of the myoma and correct placement of the serosal
      incision. What are the implications of these findings for clinical practice
      and/or further research: Intraoperative ultrasound should be more oftenly used to
      accurately locate deep intramural myomas to the end of making laparoscopy
      feasible and possibly decreasing recurrence by facilitating removal of otherwise
      unidentifiable disease.

PMID- 28764595
TI  - A case of gestational central diabetes insipidus with oligohydramnios.

PMID- 28764596
TI  - Letter to Editor re: 'Mechanochemical endovenous ablation of saphenous veins
      using the ClariVein: A systematic review' - MOCA data reporting needs to be
      tighter and standardized!

PMID- 28764597
TI  - Letters about Published Papers.

PMID- 28764598
TI  - Two cases of combination therapy with cetuximab, paclitaxel, and cisplatin for
      advanced head and neck cancer.
AB  - Two patients diagnosed with advanced head and neck cancer were treated with
      cetuximab 400 mg/m2 intravenously for one loading dose followed by 250 mg/m2 IV
      on days 1, 8, and 15 along with paclitaxel 80 mg/m2 and cisplatin 30 mg/m2
      intravenously on days 1 and 8 repeated every 21 days for three cycles (CPP).
      Maintenance cetuximab 250 mg/m2 intravenously weekly was continued following the
      aforementioned regimen for one year or until disease progression. Patient A was
      diagnosed with squamous cell carcinoma of the parotid gland treated initially
      with parotidectomy and radiation therapy. After the detection of multiple lung
      metastases, he received three cycles of CPP and maintained a stable disease after
      one year. Patient B was diagnosed with metastatic laryngeal cancer and was
      initially treated with three cycles of docetaxel, cisplatin, and continuous
      infusion fluorouracil (TPF) followed by chemoradiation with cisplatin. After one
      year, recurrence was observed, and she was treated with laryngopharyngectomy.
      After another year, recurrence was observed , and CPP was initiated. Further
      progression was noted shortly after completion of cycle 3. There are limited data
      supporting the use of regimens similar to CPP in advanced head and neck cancer.
      Further study is needed to determine the relative efficacy and safety of CPP
      compared with other regimens containing monoclonal antibodies targeting the
      epidermal growth factor receptor, taxanes, platinum agents, and/or fluorouracil.

PMID- 28764599
TI  - Evolutionary learning processes as the foundation for behaviour change.
AB  - We argue that the active ingredients of behaviour change interventions, often
      called behaviour change methods (BCMs) or techniques (BCTs), can usefully be
      placed on a dimension of psychological aggregation. We introduce evolutionary
      learning processes (ELPs) as fundamental building blocks that are on a lower
      level of psychological aggregation than BCMs/BCTs. A better understanding of ELPs
      is useful to select the appropriate BCMs/BCTs to target determinants of
      behaviour, or vice versa, to identify potential determinants targeted by a given
      BCM/BCT, and to optimally translate them into practical applications. Using these
      insights during intervention development may increase the likelihood of
      developing effective interventions - both in terms of behaviour change as well as
      maintenance of behaviour change.

PMID- 28764600
TI  - Women's expectations and experiences regarding e-health treatment: A systematic
      review.
AB  - There is a gap in knowledge of women's perceptions of e-health treatment. This
      review aims to investigate women's expectations and experiences regarding e
      health. A search was conducted in MEDLINE, EMBASE, CINAHL and PsycInfo in March
      2016. We included articles published between 2000 and March 2016, reporting on e
      health interventions. The initial search yielded 2987 articles. Eventually, 16
      articles reporting on 16 studies were included. Barriers to e-health treatment
      were lower for women than barriers to face-to-face treatment, such as feelings of
      shame and time constraints. Women were able to develop an online therapeutic
      relationship. As reduced feelings of obligation and lack of motivation were
      women's greatest challenges in completing e-health treatment, they expressed a
      wish for more support during e-health treatment, preferably blended care. e
      Health lowers the threshold for women to seek healthcare. Combining e-health
      interventions with face-to-face sessions may enhance women's motivation to
      complete treatment.

PMID- 28764601
TI  - Improved water quality and reduction of odorous compounds in anaerobic lagoon
      columns receiving pre-treated pig wastewater.
AB  - Large volumes of wastewater from confined pig production are stored in anaerobic
      lagoons. Control methods are needed to reduce air pollution by foul odors
      released from these lagoons. In a pilot-scale experiment, we evaluated the effect
      of pig wastewater pre-treatment on reducing the concentration of selected malodor
      compounds in lagoons receiving liquid from: (1) flocculant enhanced solid-liquid
      separation (SS), and (2) solid-liquid separation plus biological N treatment
      using nitrification-denitrification (SS+NDN). A conventional anaerobic lagoon was
      included as a control. Concentrations of five selected malodorous compounds
      (phenol, p-cresol, 4-ethylphenol, indole, and skatole) and water quality
      parameters (ammonia-nitrogen and chemical oxygen demand) were determined in
      lagoon effluents. The SS+NDN pretreatment was more efficient than the SS in
      reducing odorous compounds in the lagoon liquid. The SS+NDN reduced by about 99%
      the liquid concentrations of all selected compounds. An odor panel test revealed
      that SS was ineffective to reduce the human sense of malodor with respect to the
      control. Whereas the SS+NDN had the significant lowest odor intensity and
      unpleasantness. These results are supported by the strong correlations found
      between the sum of odorous compound concentration with odor panel results and
      concentrations of both ammonium-nitrogen and chemical oxygen demand in lagoon
      liquid samples.

PMID- 28764602
TI  - Improved maternity care if midwives learn to perform ultrasound: a qualitative
      study of Rwandan midwives' experiences and views of obstetric ultrasound.
AB  - BACKGROUND: Obstetric ultrasound has become an indispensable part of antenatal
      care worldwide. Although the use of ultrasound has shown benefits in the
      reduction of maternal and foetal morbidity and mortality, it has also raised many
      ethical challenges. Because of insufficient numbers of midwives in Rwanda,
      uncomplicated pregnancy care is usually provided by nurses in local health
      centres. Obstetric ultrasound is generally performed by physicians at higher
      levels of healthcare, where midwives are also more likely to be employed.
      OBJECTIVES: To explore Rwandan midwives' experiences and views of the role of
      obstetric ultrasound in relation to clinical management, including ethical
      aspects. METHODS: A qualitative study design was employed. Six focus group
      discussions were held in 2015 with 23 midwives working in maternity care in rural
      and urban areas of Rwanda, as part of the CROss Country Ultrasound Study
      (CROCUS). RESULTS: Obstetric ultrasound was experienced as playing a very
      important role in clinical management of pregnant women, but participants
      emphasised that it should not overshadow other clinical examinations. The unequal
      distribution of ultrasound services throughout Rwanda was considered a challenge,
      and access was described as low, especially in rural areas. To increase the
      quality of maternity care, some advocated strongly for midwives to be trained in
      ultrasound and for physicians to receive additional training. In general,
      pregnant women were perceived both as requesting more ultrasound examinations
      than they received, and as not being satisfied with an antenatal consultation if
      ultrasound was not performed. CONCLUSIONS: Obstetric ultrasound plays a
      significant role in maternity care in Rwanda. Increasing demand for ultrasound
      examinations from pregnant women needs to be balanced with medical indication and
      health benefits. Training of midwives to perform obstetric ultrasound and further
      training for physicians would help to address access to ultrasound for greater
      numbers of women across Rwanda. RESPONSIBLE EDITOR Virgilio Mariano Salazar
      Torres, Karolinska Institute, Sweden.

PMID- 28764603
TI  - Luteininzing hormone releasing hormones analogs in combination with tamoxifen for
      the adjuvant treatment of premenopausal women with hormone receptor positive
      breast cancer.
AB  - INTRODUCTION: The role of ovarian function suppression (OFS) through luteinizing
      hormone-releasing hormone agonists (LHRHa) in addition to tamoxifen has been
      questioned until recently. In 2015, two large clinical trials led to a paradigm
      shift in the adjuvant endocrine treatment of premenopausal women, introducing the
      use of LHRHa plus tamoxifen (or aromatase inhibitor, AI) into current clinical
      practice. Areas covered: The present review aims to provide an in-depth overview
      of the role of LHRHa+tamoxifen for the adjuvant treatment of premenopausal women
      with hormone receptor positive breast cancer (HR+BC). Expert opinion: The
      addition of LHRHa to endocrine treatment (either tamoxifen or AI) is effective in
      premenopausal women who are at high risk of relapse. To date, no clear
      recommendations are available for the choice between LHRHa+tamoxifen and LHRH+AI.
      Although recent data showed better DFS with LHRHa+AI, other issues should be
      considered: 1) approximately 20 out of 100 women do not reach complete OFS with
      LHRHa+AI; 2) there is no extended endocrine therapy option that can be applied to
      women who received 5 years of LHRHa+AI and remained premenopausal at the end of
      the fifth year. Long-term results of the SOFT-TEXT study are needed to establish
      if LHRHa+AI is superior to LHRHa+tamoxifen.

PMID- 28764604
TI  - Optical coherence tomography to guide percutaneous treatment of coronary
      bifurcation disease.
AB  - INTRODUCTION: Cardiovascular disease remains the most common cause of death
      worldwide. Enormous progress in the technology and applicability of percutaneous
      techniques to treat obstructive coronary heart disease has been made, and the
      number of percutaneous coronary interventions (PCI) is increasing. Coronary
      bifurcations are involved in a substantial number of PCIs and despite recent
      advances, bifurcation PCI remains a challenge in terms of immediate success and
      long-term outcome. Angiography has a limited capacity for showing important
      features of the 3 dimensional coronary vessel anatomy, position of stent struts
      and exact wire positions and is therefore suboptimal for guiding bifurcation PCI.
      Intracoronary optical coherence tomography (OCT) provides high resolution and the
      information gained during PCI is unprecedented compared with angiography guidance
      and intravascular ultrasound. Areas covered: This review will provide an overview
      of the use of OCT to guide bifurcation-PCI. Expert commentary: OCT is a promising
      guide for bifurcation-PCI at each individual step: from planning the strategy
      (provisional versus two-stent strategy), to guidance during PCI, and finally
      checking the interventional result. Until dedicated randomized trails are
      complete, we recommend OCT guidance for interventions in complex coronary
      bifurcation disease and for imaging when unexpected procedural events occur.

PMID- 28764605
TI  - Impact of oestrogen and progesterone receptor expression in the cancer cells and
      myometrium on survival of patients with endometrial cancer.
AB  - Loss of oestrogen receptor (ER) and progesterone receptor (PR) expression in
      endometrial cancer cells indicates poor prognosis. The aim of this study was to
      determine the correlation of ER and PR expression in cancer cells and the
      surrounding myometrium with the disease progression. Immunohistochemical
      expression of ER and PR was detected in cancer and myometrial cells of patients
      with EC. ER was detected in 65.2% of cancer cells and in 88.4% of myometrial
      cells. PR was detected in 59.4% of cancer cells and in 84.1% of myometrial cells.
      The 5-year overall survival (OS) was 76.8%. Patients with ER and PR negative EC
      had a shorter period until recurrence (p = .013 and .043) and shorter OS (p =
      .011 and .066) than those with ER and PR positive cancer. Negative ER and PR
      status in EC has an impact on recurrence and poor OS. The status of hormone
      receptors in myometrium may be useful in disease prognosis. Impact Statement The
      status of hormone receptors in endometrial cancer has been the subject of
      numerous studies and loss of hormone receptors indicates higher tumor grade and
      higher clinical stage, lympho-vascular space invasion and deeper myometrial
      invasion. Although, the communication between the endometrium and myometrium is
      crucial under physiological conditions, the status of hormone receptors in the
      myometrium and its significance in cancer progression is poorly studied. Our
      results showed that loss of ER in the myometrium indicate poor prognosis. The
      assessment of hormone receptor status in myometrium might be useful in predicting
      the course of the disease. Results of our research support the theory that
      stromal and myometrial cells may contribute to tumorigenesis in endometrial
      cancer. Better understanding of ER/PR expression in myometrial cells is needed,
      and our research opens new possibilities for identification of key pathways and
      new potential target molecules in EC prognosis and treatment. It is probable that
      future classification of endometrial cancer will rely on molecular sub-typing,
      where the status of hormone receptors in the myometrium might play an important
      role.

PMID- 28764606
TI  - Low-dose radiation-induced risk in spermatogenesis.
AB  - PURPOSE: To discuss low-dose radiation-induced risks to male fertility focusing
      on potential mechanisms of low-dose radiation-induced damage on spermatogenesis,
      epidemiological studies of environmental radiation effects on sperm parameters
      and transgenerational effects following exposure of spermatogonial stem cells
      (SSCs). BACKGROUND: Spermatogenesis produces mature male gametes, spermatozoa,
      which fertilize their counterpart female gametes, oocytes. The robust maintenance
      system of spermatogenesis is essential for genomic conservation; however, male
      fertility can be readily impacted by exposure to environmental, chemical and
      physical factors including ionizing radiation. The mammalian testes are known to
      be radiosensitive yet the underlying molecular mechanisms of low-dose radiation
      induced risks for spermatogenesis remain unclear. Furthermore, evidence
      characterizing transgenerational effects following exposure of SSCs remain
      controversial. CONCLUSIONS: Current concerns over the possible effects of low
      dose radiation exposure on spermatogenesis requires further elucidation that may
      be resolved comparing and integrating observed experimental and epidemiological
      data.

PMID- 28764607
TI  - Recycling and Reinforcing Intimomedial Flap of the Infrarenal Aorta Using
      Anterior Longitudinal Ligament in Patients With Acute Trauma With Bowel Injuries.
AB  - We present a patient with blunt abdominal trauma with severe acute right limb
      ischemia and clinical signs of diffuse peritonitis. Computed tomography
      angiography showed circumferential dissection of the infrarenal aorta with
      occlusion of the right common iliac artery. We opted for simultaneous abdomen
      exploration and open repair of injured aorta. Critical weakening of the aortic
      wall with imminent rupture was identified intraoperatively. Aortotomy cranially
      from bifurcation showed circumferential intimomedial dissection. The fixation of
      fragile intimomedial flap of aortic dissection was achieved with reinforcement
      using an anterior longitudinal ligament. The long aortoiliac arteriotomy was
      repaired using a great saphenous vein patch. Patient had uneventful postoperative
      course and was discharged after 7 days. In patients with abdominal polytrauma
      with peritonitis, and no available endovascular tools, open surgery for
      circumferential aortic dissection is possible and successful. Described
      reinforcement of the posterior aortic wall to the anterior longitudinal ligament
      should be added to the armamentarium of aortic injury treatment.

PMID- 28764608
TI  - Rare Post-Tonsillectomy Internal Carotid Artery Pseudoaneurysm: Management by
      Parent Artery Occlusion Using Detachable Balloons.
AB  - Iatrogenic cervical internal carotid artery pseudoaneurysm is a rare and
      potentially lethal complication following tonsillectomy. It can be complicated by
      thromboembolism, mass effect and eventually may rupture leading to death. Various
      endovascular treatment options are available for the management of these
      pseudoaneurysms, including coil embolization, detachable balloon occlusion, or
      stent graft placement. Parent artery occlusion using detachable balloons can be a
      therapeutic option in a subset of patients. However, evaluation of cross
      circulation with preprocedure balloon test occlusion is imperative in such cases.

PMID- 28764609
TI  - Endovascular Management for Symptomatic Chronic Mesenteric Ischemia: A Single
      Center Experience.
AB  - BACKGROUND: Chronic mesenteric ischemia (CMI) is an uncommon condition
      encountered by clinicians. Presentation may vary from asymptomatic to classical
      intestinal ischemia, although a clear pathophysiology has yet to be elucidated.
      Here, we have presented our institution's experience in the management of
      symptomatic CMI. METHODS: From February 2007 to February 2016, a retrospective
      study was performed of all consecutive patients with symptomatic CMI managed by
      endovascular treatment (ET). We reviewed these patients' demographics,
      comorbidities, clinical presentations, and treatment modalities. Perioperative
      and midterm outcomes included technical success, clinical symptom relief,
      complications, symptomatic recurrence, mortality, restenosis, and reintervention.
      RESULTS: Thirty-five mesenteric arteries (74.3% stenotic/25.7% occluded)
      identified in 32 patients (12 females, 20 males) were treated with endovascular
      procedures. There were no 30-day deaths; the perioperative complication rate was
      12.5%. Overall, the median postprocedural time to symptom relief was 7.6 days
      (range: 1-30 days). Twenty-two (68.8%) had complete remission of symptom, whereas
      7 (21.9%) had partial improvement in symptom after ET. After a mean follow-up of
      35.4 (25.9) months, 5 (15.6%) patients developed recurrent symptoms, with 4
      requiring reinterventions. The primary patency was 93.7%, 82.6%, and 73.1% at 12,
      24, and 36 months, respectively, and the freedom from symptomatic recurrence was
      90.6%, 84.0%, 84.0%, and 84.0% at 6, 12, 24, and 36 months, respectively.
      CONCLUSIONS: Endovascular treatment for patients with CMI had a high technical
      success rate and satisfactory clinical outcomes. Symptomatic recurrence was not
      frequent but found mainly within 12 months following the initial procedure.

PMID- 28764610
TI  - Synovial Sarcoma Mimicking Pleomorphic Hyalinizing Angiectatic Tumor of Soft
      Parts: A Case Report.
AB  - Synovial sarcoma is a high-grade sarcoma commonly affecting young adults. The
      sites of involvement include soft tissue near joints, lung, pleura, mediastinum,
      larynx, kidney, and buttocks. Histologic types include monophasic, biphasic, and
      undifferentiated. We report a unique case of synovial sarcoma with low-grade
      histologic features mimicking pleomorphic hyalinizing angiectatic tumor (PHAT)
      with indolent behavior for a period of 10 years. The tumor showed angiectatic
      blood vessels with fibrinous cuffing, hypocellular and hypercellular spindle cell
      areas with rare mitoses, and focal atypia in a myxoid background. TLE1 was
      positive with SYT gene translocation detected on fluorescent in situ
      hybridization. Cases of myxoinflammatory fibroblastic sarcoma and
      myxofibrosarcoma have been reported as exhibiting histologic features of PHAT.
      However, to the best of our knowledge, cases of synovial sarcoma mimicking PHAT
      have not been reported.

PMID- 28764611
TI  - Incidence of renal Fanconi syndrome in patients taking antiretroviral therapy
      including tenofovir disoproxil fumarate.
AB  - The objective of this study was to determine the incidence and predictors of
      Fanconi Syndrome (FS) in a cohort of patients taking tenofovir disoproxil
      fumarate (TDF). Clinical records and laboratory investigations from patients
      receiving TDF between 2002 and 2016 were extracted. FS was defined as
      normoglycaemic glycosuria and proteinuria and at least one other marker of renal
      dysfunction. Regression analysis was performed with time to development of FS and
      the following covariates: ritonavir co-administration, age, gender, co
      morbidities (hypertension, hyperlipidaemia, diabetes, viral hepatitis), CD4 cell
      count nadir and baseline eGFR. One thousand and forty-four patients received TDF
      without ritonavir and 398 patients with ritonavir. Thirteen cases of FS were
      identified with a mean duration of exposure of 55 months. The incidence of FS was
      1.09/1000PY (0.54-1.63) of TDF exposure (without ritonavir) and 5.50/1000PY (3.66
      7.33) of TDF-ritonavir co-administration (p=0.0057). The adjusted hazards ratio
      for ritonavir co-administration was 4.71 (1.37-16.14, p=0.014). Known risk
      factors for chronic kidney disease were not associated with development of FS.
      Ritonavir co-administration, but not other factors, is associated with a greater
      risk of FS. FS developed late. Known risk factors for chronic kidney disease and
      length of treatment are not useful for identifying patients most at risk of
      developing FS in patients taking TDF.

PMID- 28764612
TI  - Influencing the importance of health, partners, and hygiene among Zambian women.
AB  - Intravaginal practices (IVPs) are common in Zambia and are usually practiced for
      hygiene, partner pleasure, and health. IVPs are associated with HIV acquisition,
      changes in the vaginal flora, and bacterial vaginosis (BV), making it important
      to understand the decision-making process behind IVP engagement. The Women's and
      Sexual Health (WASH) intervention decreased IVP engagement among HIV-infected
      Zambian women, though change in reasons for engagement has not been assessed. We
      used conjoint analysis (CA) to quantify the decision-making process of IVP
      engagement and evaluated how the WASH intervention impacted these factors.
      Participants were N = 84 women (37 +/- 8 years old) randomized to WASH (n = 46)
      or standard of care plus (SOC+; n = 38) who completed demographic measures and a
      CA questionnaire at baseline, six months, and 12 months to quantify the
      importance placed on hygiene, partner pleasure, and health. The importance placed
      on health increased from baseline to six months (15.5 versus 25.1; p < 0.001) and
      from baseline to 12 months (15.5 versus 50.5; p < 0.001), and was higher in SOC+
      at six months (19.9 versus 30.3; p = 0.003). Hygiene importance decreased from
      baseline (63.6) to six months (50.3), and from baseline to 12 months (26.1), and
      was higher in the experimental arm at six months (56.1) compared to SOC+ (44.6; p
      = 0.029). Importance placed on partner pleasure did not change over time in
      either group. Findings suggest that both groups exhibited an increase in the
      importance placed on health and a decrease on hygiene importance for IVP
      engagement, suggesting that SOC+ may be sufficient to promote attitude changes
      that may facilitate IVP discontinuation and may prove to be more cost effective
      by using fewer monetary resources. Findings highlight the potential of
      interventions to influence attitudes toward IVPs and provide novel avenues for
      research to improve the design and conduct of interventions aimed at reducing
      IVPs among Zambian women and contribute to HIV prevention efforts.

PMID- 28764613
TI  - Correlates of engagement in group sex events among men who have sex with men in
      London who use geosocial-networking smartphone applications.
AB  - Men who have sex with men (MSM) who attend group sex events (GSEs) tend to also
      engage in high-risk sexual behaviors and substance use that may place them at
      additional increased risk for becoming infected with HIV. These sorts of events
      may be facilitated by the use of geosocial-networking smartphone applications,
      where MSM may have access to a large virtual pool of potential partners. The
      purpose of the current study was to examine the prevalence of recent engagement
      in GSEs and its demographic and behavioral correlates among a sample of MSM ( n =
      202). Log-binomial models were fit to assess correlates of engagement in GSEs in
      the preceding three months. Overall, 42.6% had engaged in a GSE in the preceding
      three months. In multivariable models, the use of inhalant nitrites (PR: 2.239;
      95% CI: 1.119, 4.848; p = .024) and methamphetamine (PR: 7.601; 95% CI: 2.340,
      24.691; p = .001) were associated with recent engagement in GSEs. Given the high
      prevalence of these potentially high-risk behaviors, future research should be
      conducted to examine the concurrent use of substance use and condom use at the
      GSEs to develop appropriate risk reduction interventions.

PMID- 28764614
TI  - Quantitative evaluation of arteriovenous malformation hemodynamic changes after
      endovascular treatment using parametric color coding: A case series study.
AB  - Background Brain arteriovenous malformations (AVMs) are complex vascular lesions.
      Endovascular treatment results are usually measured by calculating the volume
      reduction of the lesions. Nevertheless, vascular flow quantification seems a more
      physiologically accurate way of measuring endovascular results. We evaluated the
      use of parametric color coding (PCC) with digital subtraction angiography (DSA),
      in order to determine the feasibility of PCC to detect and measure the impact of
      AVM endovascular treatment-induced changes using real-time hemodynamic
      parameters. Methods and results Supratentorial brain AVM treatment was evaluated
      in 29 patients over the course of 38 sessions. Using regions of interest (ROIs)
      at the carotid siphon, arterial feeder, drainage vein and venous sinus, we found
      significant increase in time to peak (TTP) values at the arterial feeder,
      drainage vein and venous sinus. We compared TTP in four different embolization
      volume groups: I (0-25%), II (26-50%), III (51-75%) and IV (76-100%). We found
      significant differences between groups and a moderate correlation between
      embolization percentages, as well as an increase in TTP at the main vein ROI; but
      not in the arterial side or sinus. Conclusions Brain AVM endovascular treatment
      results can be quantified in vivo with PCC. PCC is capable of detecting
      hemodynamic changes after brain AVM endovascular treatment, that may reflect flow
      drop, and it is correlated with volume embolization.

PMID- 28764615
TI  - Cerebral tuberculosis in a patient with systemic lupus erythematosus following
      cyclophosphamide treatment: a case report.
AB  - Central nervous system (CNS) tuberculosis (TB) is a rare but catastrophic event
      in patients with systemic lupus erythematosus (SLE). Here we report a case of
      cerebral TB in a patient with lupus myocarditis and nephritis, following
      cyclophosphamide immunosuppression. To our knowledge this is the first reported
      case of cerebral TB in SLE in a non-endemic country. A 31-year-old female with
      SLE and a history of regular travel to Kenya presented to our centre with
      clinical features of acute heart failure. She was diagnosed with severe lupus
      myocarditis, and a renal biopsy also confirmed lupus nephritis. Prior to
      admission, she had also had a cough, fever and weight loss and was under
      investigation for suspected TB infection. She was treated with ivabradine, beta
      blockers and diuretics together with methylprednisolone and cyclophosphamide
      immunosuppression. Subsequent sputum cultures confirmed TB and she was commenced
      on triple therapy. Despite this, she developed confusion, dizziness, blurred
      vision and fluctuating consciousness. Magnetic resonance imaging (MRI) and lumbar
      puncture revealed CNS TB infection resulting in meningitis. This was later
      complicated by obstructive hydrocephalus due to TB abscesses. A
      ventriculoperitoneal (VP) shunt was inserted and TB medications were given
      intravenously (IV) with dexamethasone. Following a prolonged hospital admission,
      the patient eventually recovered and rituximab treatment was used to control her
      SLE. TB infection has been associated with SLE flares. It is likely in this case
      that TB exacerbated a lupus flare and subsequent immunosuppression resulted in
      mycobacterial dissemination to the CNS. Systemic and CNS features of TB and SLE
      are difficult to distinguish and their contemporaneous management represents a
      diagnostic and therapeutic challenge.

PMID- 28764616
TI  - Effector T-cells are expanded in systemic lupus erythematosus patients with high
      disease activity and damage indexes.
AB  - Background and objectives T-cell activation may be one of the pathogenic
      mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic
      stimulation, T-cells undergo different modifications, leading to the
      differentiation into effector memory T-cells (CCR7-CD45RA-) and terminally
      differentiated effector memory (TDEM) T-cells (CCR7-CD45RA+). Similarly, down
      modulation of CD28 may lead to the expansion of the CD28- T-cells, a
      subpopulation with peculiar effector activities. The aim of this study was the
      characterization of T-cell phenotype in a cohort of patients with SLE according
      to disease activity and damage index. Materials and methods Phenotypic analysis
      of peripheral blood T lymphocytes of 51 SLE patients and 21 healthy controls was
      done by flow-cytometry. SLE disease activity was evaluated by SLE Disease
      Activity Index-2000 (SLEDAI-2K) and damage by the Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology damage index (SDI). The
      variations between different groups were evaluated by Mann-Whitney test.
      Bonferroni correction was applied to adjust for multiple comparisons ( padj).
      Spearman rank test was used to evaluate the correlations between quantitative
      variables. Results CD4+ lymphopenia was found among SLE patients. Patients showed
      a trend for a higher percentage of TDEM among the CD4+ T-cell subpopulation in
      comparison with healthy controls ( p = .04). SLE patients were divided into two
      groups according to disease activity: patients with SLEDAI-2K >= 6 ( n = 13) had
      a higher percentage of circulating CD4+ T-cells with CD28- phenotype ( padj =
      .005) as well as those with an effector memory ( padj = .004) and TDEM ( padj =
      .002) phenotype and a trend of decrease of regulatory T-cells (TREGs) ( p = .02),
      in comparison with patients with low disease activity ( n = 38). Patients with
      damage (SDI >= 1) tended to show an expansion of TDEM among CD4+ T-cells as
      compared with patients with no damage ( p = .01). In SLE patients an inverse
      correlation was found between the percentages of TREGs and those of TDEM ( p <
      .01) or CD4 + CD28- ( p < .01) T-cells. Conclusions CD4+ T-cell subpopulations
      displaying phenotype characteristics of effector lymphocytes are proportionally
      expanded in patients with active SLE and a higher damage index. These findings
      may suggest a role of effector T-cells in the pathogenesis of the disease and in
      the mechanisms of damage in SLE.

PMID- 28764617
TI  - Discordance of patient and physician health status concerns in systemic lupus
      erythematosus.
AB  - Objectives To compare the health status concerns of patients with systemic lupus
      erythematosus (SLE) and of their physicians. Methods Cross-sectional
      questionnaire study of SLE patients and their treating physicians at a tertiary
      disease-specific outpatient clinic. Patients and physicians completed a
      questionnaire regarding their concern about specific disease manifestations and
      impact on quality of life. For each item, degree of concern was rated on a five
      point Likert scale and summarized as median (interquartile range). Ratings
      between patients and physicians were compared using Mann-Whitney U tests. Results
      A total of 84 patients and 21 physicians participated. Patients' predominant
      concerns centred on function and fatigue, whereas physicians' concerns focused on
      SLE-related organ complications. Of the 10 highest ranked patient concerns, only
      two were common to the 10 highest ranked physician concerns, while physicians
      rated seven significantly differently; all 10 highest ranked physician concerns
      were rated significantly lower by patients. The three highest ranked patient
      concerns (fatigue, pain and feeling worn out) were routinely assessed by 47.6%,
      42.9% and 9.5% of physicians, respectively. Conclusion There was significant
      discordance between SLE patient and physician health status concerns. Items which
      were ranked highly by patients were not assessed consistently by physicians,
      highlighting a significant gap in healthcare communication.

PMID- 28764618
TI  - Hydroxychloroquine in the primary thrombosis prophylaxis of antiphospholipid
      antibody positive patients without systemic autoimmune disease.
AB  - Objective The objective of this study was to determine the efficacy of
      hydroxychloroquine (HCQ) in the primary thrombosis prevention of antiphospholipid
      antibody (aPL)-positive patients with no other systemic autoimmune diseases.
      Methods Under the auspices of Antiphospholipid Syndrome Alliance for Clinical
      Trials and International Networking, a multicenter, international, randomized
      controlled trial (RCT) was initiated, in which persistently aPL-positive but
      thrombosis-free patients without systemic autoimmune diseases were randomized to
      receive HCQ or no treatment in addition to their standard regimen. The primary
      objective was the efficacy of HCQ in preventing the first thrombosis. The
      secondary objectives were the thrombosis incidence rate, and the effects of HCQ
      on aPL profile and mortality rate. Patients were risk-stratified based on
      antiplatelet agent use. The goal was to follow patients every 6 months for 5
      years. Results We recruited 20 persistently aPL-positive patients (female: 19,
      mean age: 46.6 +/- 9.9 years, and baseline antiplatelet medication: 14); 9/20
      were randomized to HCQ. During the mean follow-up of 1.7 years, no patients
      developed thrombosis or a serious adverse event. The study was terminated early
      due to the low recruitment rate, exacerbated by the prolonged manufacturing
      shortage and significant price increase of HCQ in the United States. Conclusion
      Given that a small number of patients with a relatively short follow-up were
      enrolled in our RCT, and no patients developed thrombosis, we cannot accurately
      assess the effectiveness of HCQ for primary thrombosis prevention in persistently
      aPL-positive patients with no other systemic autoimmune diseases. Our experience
      suggests that conducting an international RCT, especially without pharmaceutical
      support, is an extremely challenging undertaking.

PMID- 28764619
TI  - Assisted reproductive technology in Australia and New Zealand: cumulative live
      birth rates as measures of success.
AB  - OBJECTIVES: To estimate cumulative live birth rates (CLBRs) following repeated
      assisted reproductive technology (ART) ovarian stimulation cycles, including all
      fresh and frozen/thaw embryo transfers (complete cycles). DESIGN, SETTING AND
      PARTICIPANTS: Prospective follow-up of 56 652 women commencing ART in Australian
      and New Zealand during 2009-2012, and followed until 2014 or the first treatment
      dependent live birth. MAIN OUTCOME MEASURES: CLBRs and cycle-specific live birth
      rates were calculated for up to eight cycles, stratified by the age of the women
      (< 30, 30-34, 35-39, 40-44, > 44 years). Conservative CLBRs assumed that women
      discontinuing treatment had no chance of achieving a live birth if had they
      continued treatment; optimal CLBRs assumed that they would have had the same
      chance as women who continued treatment. RESULTS: The overall CLBR was 32.7% (95%
      CI, 32.2-33.1%) in the first cycle, rising by the eighth cycle to 54.3% (95% CI,
      53.9-54.7%) (conservative) and 77.2% (95% CI, 76.5-77.9%) (optimal). The CLBR
      decreased with age and number of complete cycles. For women who commenced ART
      treatment before 30 years of age, the CLBR for the first complete cycle was 43.7%
      (95% CI, 42.6-44.7%), rising to 69.2% (95% CI, 68.2-70.1%) (conservative) and
      92.8% (95% CI, 91.6-94.0) (optimal) for the seventh cycle. For women aged 40-44
      years, the CLBR was 10.7% (95% CI, 10.1-11.3%) for the first complete cycle,
      rising to 21.0% (95% CI, 20.2-21.8%) (conservative) and 37.9% (95% CI, 35.9
      39.9%) (optimal) for the eighth cycle. CONCLUSION: CLBRs based on complete cycles
      are meaningful estimates of ART success, reflecting contemporary clinical
      practice and encouraging safe practice. These estimates can be used when
      counselling patients and to inform public policy on ART treatment.

PMID- 28764620
TI  - The Australian Snakebite Project, 2005-2015 (ASP-20).
AB  - OBJECTIVE: To describe the epidemiology, treatment and adverse events after
      snakebite in Australia. DESIGN: Prospective, multicentre study of data on
      patients with snakebites recruited to the Australian Snakebite Project (2005
      2015) and data from the National Coronial Information System. Setting,
      participants: Patients presenting to Australian hospitals with suspected or
      confirmed snakebites from July 2005 to June 2015 and consenting to participation.
      MAIN OUTCOME MEASURES: Demographic data, circumstances of bites, clinical effects
      of envenoming, results of laboratory investigations and snake venom detection kit
      (SVDK) testing, antivenom treatment and adverse reactions, time to discharge,
      deaths. RESULTS: 1548 patients with suspected snakebites were enrolled, including
      835 envenomed patients (median, 87 per year), for 718 of which the snake type was
      definitively established, most frequently brown snakes (41%), tiger snakes (17%)
      and red-bellied black snakes (16%). Clinical effects included venom-induced
      consumption coagulopathy (73%), myotoxicity (17%), and acute kidney injury (12%);
      severe complications included cardiac arrest (25 cases; 2.9%) and major
      haemorrhage (13 cases; 1.6%). There were 23 deaths (median, two per year),
      attributed to brown (17), tiger (four) and unknown (two) snakes; ten followed out
      of-hospital cardiac arrests and six followed intracranial haemorrhages. Of 597
      SVDK test results for envenomed patients with confirmed snake type, 29 (4.9%)
      were incorrect; 133 of 364 SVDK test results for non-envenomed patients (36%)
      were false positives. 755 patients received antivenom, including 49 non-envenomed
      patients; 178 (24%), including ten non-envenomed patients, had systemic
      hypersensitivity reactions, of which 45 (6%) were severe (hypotension,
      hypoxaemia). Median total antivenom dose declined from four vials to one, but
      median time to first antivenom was unchanged (4.3 hours; IQR, 2.7-6.3 hours).
      CONCLUSIONS: Snake envenoming is uncommon in Australia, but is often severe.
      SVDKs were unreliable for determining snake type. The median antivenom dose has
      declined without harming patients. Improved early diagnostic strategies are
      needed to reduce the frequently long delays before antivenom administration.

PMID- 28764622
TI  - Specialist outreach services in regional and remote Australia: key drivers and
      policy implications.

PMID- 28764623
TI  - Performance data and informed consent: a duty to disclose?

PMID- 28764624
TI  - Three-dimensional printing in medicine.

PMID- 28764625
TI  - Understanding statistical principles in correlation, causation and moderation in
      human disease.

PMID- 28764626
TI  - How to measure a QT interval.

PMID- 28764627
TI  - Assisted reproductive technologies: new guidance for women and doctors is
      welcome.

PMID- 28764628
TI  - Snakebites: reducing their international impact.

PMID- 28764629
TI  - Risks of using medical record and administrative data for prognostic models.

PMID- 28764630
TI  - Optimising assessment of kidney function when managing localised renal masses.
AB  - Increased early and incidental detection, improved surgical techniques and
      technological advancement mean that the management of renal mass lesions is
      constantly evolving. The treatment of choice for renal mass lesions has
      historically been radical nephrectomy. Partial nephrectomy is now recommended for
      localised renal masses, owing to favourable renal functional outcomes. Ablative
      renal surgery confers a significant risk of chronic kidney disease. There are few
      studies assessing long term outcomes of nephrectomy on renal outcomes, and
      virtually no studies assessing long term outcomes for less invasive therapies
      such as ablation. Unless a renal mass is clearly benign on imaging, management
      decisions will be made with an assumption of malignancy. The content of this
      review applies to both benign and malignant renal mass lesions. We advocate for
      improved strategies for kidney function assessment and risk stratification, early
      targeted referral, and regular screening for chronic kidney disease for all
      patients after surgery.

PMID- 28764631
TI  - What risks do herbal products pose to the Australian community?

PMID- 28764632
TI  - What risks do herbal products pose to the Australian community?

PMID- 28764633
TI  - What risks do herbal products pose to the Australian community?

PMID- 28764635
TI  - Around the universities and research institutes.

PMID- 28764634
TI  - True to his calling.

PMID- 28764637
TI  - Invasive anisakiasis by the parasite Anisakis pegreffii (Nematoda: Anisakidae):
      diagnosis by real-time PCR hydrolysis probe system and immunoblotting assay.
AB  - BACKGROUND: Anisakiasis is a fish-borne zoonosis caused by Anisakis spp. larvae.
      One challenging issue in the diagnosis of anisakiasis is the molecular detection
      of the etiological agent even at very low quantity, such as in gastric or
      intestinal biopsy and granulomas. Aims of this study were: 1) to identify three
      new cases of invasive anisakiasis, by a species-specific Real-time PCR probe
      assay; 2) to detect immune response of the patients against the pathogen.
      METHODS: Parasite DNA was extracted from parasites removed in the three patients.
      The identification of larvae removed at gastric and intestinal level from two
      patients was first obtained by sequence analysis of mtDNA cox2 and EF1 alpha-1 of
      nDNA genes. This was not possible in the third patient, because of the very low
      DNA quantity obtained from a single one histological section of a surgically
      removed granuloma. Real-time PCR species-specific hydrolysis probe system, based
      on mtDNA cox2 gene, was performed on parasites tissue of the three cases. IgE,
      IgG4 and IgG immune response against antigens A. pegreffii by Immunoblotting
      assay was also studied. RESULTS: According to the mtDNA cox2 and the EF1 alpha -
      1 nDNA sequence analysis, the larvae from stomach and intestine of two patients
      were assigned to A. pegreffii. The Real-time PCR primers/probe system, showed a
      fluorescent signal at 510 nm for A. pegreffii, in all the three cases. In
      Immunoblotting assay, patient CC1 showed IgE, IgG4 reactivity against Ani s 13
      like and Ani s 7-like; patient CC2 revealed only IgG reactivity against Ani s 13
      like and Ani s 7-like; while, the third patient showed IgE and IgG reactivity
      against Ani s 13-like, Ani s 7-like and Ani s 1-like. CONCLUSION: The Real-time
      PCR assay, a more sensitive method than direct DNA sequencing for the accurate
      and rapid identification of etiological agent of human anisakiasis, was
      successfully assessed for the first time. The study also highlights the
      importance to use both molecular and immunological tools in the diagnosis of
      human anisakiasis, in order to increase our knowledge about the pathological
      findings and immune response related to the infection by zoonotic species of the
      genus Anisakis.

PMID- 28764638
TI  - Contribution of rare and low-frequency whole-genome sequence variants to complex
      traits variation in dairy cattle.
AB  - BACKGROUND: Whole-genome sequencing and imputation methodologies have enabled the
      study of the effects of genomic variants with low to very low minor allele
      frequency (MAF) on variation in complex traits. Our objective was to estimate the
      proportion of variance explained by imputed sequence variants classified
      according to their MAF compared with the variance explained by the pedigree-based
      additive genetic relationship matrix for 17 traits in Nordic Holstein dairy
      cattle. RESULTS: Imputed sequence variants were grouped into seven classes
      according to their MAF (0.001-0.01, 0.01-0.05, 0.05-0.1, 0.1-0.2, 0.2-0.3, 0.3
      0.4 and 0.4-0.5). The total contribution of all imputed sequence variants to
      variance in deregressed estimated breeding values or proofs (DRP) for different
      traits ranged from 0.41 [standard error (SE) = 0.026] for temperament to 0.87 (SE
      = 0.011) for milk yield. The contribution of rare variants (MAF < 0.01) to the
      total DRP variance explained by all imputed sequence variants was relatively
      small (a maximum of 12.5% for the health index). Rare and low-frequency variants
      (MAF < 0.05) contributed a larger proportion of the explained DRP variances
      (>13%) for health-related traits than for production traits (<11%). However, a
      substantial proportion of these variance estimates across different MAF classes
      had large SE, especially when the variance explained by a MAF class was small.
      The proportion of DRP variance that was explained by all imputed whole-genome
      sequence variants improved slightly compared with variance explained by the 50 k
      Illumina markers, which are routinely used in bovine genomic prediction. However,
      the proportion of DRP variance explained by imputed sequence variants was lower
      than that explained by pedigree relationships, ranging from 1.5% for milk yield
      to 37.9% for the health index. CONCLUSIONS: Imputed sequence variants explained
      more of the variance in DRP than the 50 k markers for most traits, but explained
      less variance than that captured by pedigree-based relationships. Although in
      humans partitioning variants into groups based on MAF and linkage disequilibrium
      was used to estimate heritability without bias, many of our bovine estimates had
      a high SE. For a reliable estimate of the explained DRP variance for different
      MAF classes, larger sample sizes are needed.

PMID- 28764639
TI  - Antithrombotic treatment during coronary angioplasty after failed thrombolysis:
      strategies and prognostic implications. Results of the RESPIRE registry.
AB  - BACKGROUND: Thrombolysis is still used when primary angioplasty is delayed for a
      long time, but 25%-30% of patients require rescue angioplasty (RA). There are no
      established recommendations for antithrombotic management in RA. This registry
      analyzes regimens for antithrombotic management. METHODS: A retrospective,
      multicenter, observational registry of consecutive patients treated with RA at 8
      hospitals. All variables were collected and follow-up took place at 6 months.
      RESULTS: The study included 417 patients. Antithrombotic therapy in RA was: no
      additional drugs 22.3%, unfractionated heparin (UFH) 36.6%, abciximab 15.5%,
      abciximab plus UFH 10.5%, bivalirudin 5.7%, enoxaparin 4.3%, and others 4.7%.
      Outcomes at 6 months were: mortality 9.1%, infarction 3.3%, definite or probable
      stent thrombosis 4.3%, revascularization 1.9%, and stroke 0.5%. Mortality was
      related to cardiogenic shock, age > 75 years, and anterior location. The stent
      thrombosis rate was highest with bivalirudin (12.5% at 6 months). The incidence
      of bleeding at admission was high (14.8%), but most cases were not severe (82%
      BARC <=2). Variables independently associated with bleeding were: femoral access
      (OR 3.30; 95% CI 1.3-8.3: p = 0.004) and post-RA abciximab infusion (OR 2.26; 95%
      CI 1.02-5: p = 0.04). CONCLUSIONS: Antithrombotic treatment regimens in RA vary
      greatly, predominant strategies consisting of no additional drugs or UFH 70 U/kg.
      No regimen proved predictive of mortality, but bivalirudin was related to more
      stent thrombosis. There was a high incidence of bleeding, associated with post-RA
      abciximab infusion and femoral access.

PMID- 28764640
TI  - Geographical differences in perinatal health and child welfare in the
      Netherlands: rationale for the healthy pregnancy 4 all-2 program.
AB  - BACKGROUND: Geographical inequalities in perinatal health and child welfare
      require attention. To improve the identification, and care, of mothers and young
      children at risk of adverse health outcomes, the HP4All-2 program was developed.
      The program consists of three studies, focusing on creating a continuum for risk
      selection and tailored care pathways from preconception and antenatal care
      towards 1) postpartum care, 2) early childhood care, as well as 3)
      interconception care. The program has been implemented in ten municipalities in
      the Netherlands, aiming to target communities with a relatively disadvantageous
      position with regard to perinatal and child health outcomes. To delineate the
      position of the ten participating municipalities, we present municipal and
      regional differences in the prevalence of perinatal mortality, perinatal
      morbidity, children living in deprived neighbourhoods, and children living in
      families on welfare. METHODS: Data on all singleton births in the Netherlands
      between 2009 and 2014 were analysed for the prevalence of perinatal mortality and
      morbidity. In addition, national data on children living in deprived
      neighbourhoods and children living in families on welfare between 2009 and 2012
      were analysed. The prevalence of these outcomes were calculated and ranked for 62
      geographical areas, the 50 largest municipalities and the 12 provinces, to
      determine the position of the municipalities that participate in HP4All-2.
      RESULTS: Considerable geographical differences were present for all four
      outcomes. The municipalities that participate in HP4All-2 are among the 25
      municipalities with the highest prevalence of perinatal mortality, perinatal
      morbidity, children living in deprived neighbourhoods, or children in families on
      welfare. CONCLUSION: This study illustrates geographical differences in perinatal
      health and/or child welfare outcomes and demonstrates that the HP4All-2 program
      targets municipalities with a relative unfavourable position. By targeting these
      municipalities, the program is expected to contribute most to improving the care
      for young children and their mothers at risk, and hence to reducing their risks
      and health inequalities.

PMID- 28764641
TI  - Prediction of new onset of end stage renal disease in Chinese patients with type
      2 diabetes mellitus - a population-based retrospective cohort study.
AB  - BACKGROUND: Since diabetes mellitus (DM) is the leading cause of end stage renal
      disease (ESRD), this study aimed to develop a 5-year ESRD risk prediction model
      among Chinese patients with Type 2 DM (T2DM) in primary care. METHODS: A
      retrospective cohort study was conducted on 149,333 Chinese adult T2DM primary
      care patients without ESRD in 2010. Using the derivation cohort over a median of
      5 years follow-up, the gender-specific models including the interaction effect
      between predictors and age were derived using Cox regression with a forward
      stepwise approach. Harrell's C-statistic and calibration plot were applied to the
      validation cohort to assess discrimination and calibration of the models.
      RESULTS: Prediction models showed better discrimination with Harrell's C
      statistics of 0.866 (males) and 0.862 (females) and calibration power from the
      plots than other established models. The predictors included age, usages of anti
      hypertensive drugs, anti-glucose drugs, and Hemogloblin A1c, blood pressure,
      urine albumin/creatinine ratio (ACR) and estimated glomerular filtration rate
      (eGFR). Specific predictors for male were smoking and presence of sight
      threatening diabetic retinopathy while additional predictors for female included
      longer duration of diabetes and quadratic effect of body mass index. Interaction
      factors with age showed a greater weighting of insulin and urine ACR in younger
      males, and eGFR in younger females. CONCLUSIONS: Our newly developed gender
      specific models provide a more accurate 5-year ESRD risk predictions for Chinese
      diabetic primary care patients than other existing models. The models included
      several modifiable risk factors that clinicians can use to counsel patients, and
      to target at in the delivery of care to patients.

PMID- 28764642
TI  - The susceptibility of FSHB -211G > T and FSHR G-29A, 919A > G, 2039A > G
      polymorphisms to men infertility: an association study and meta-analysis.
AB  - BACKGROUND: Male infertility is a complex disorder caused by genetic,
      developmental, endocrine, or environmental factors as well as unknown etiology.
      Polymorphisms in the follicle stimulating hormone beta subunit (FSHB)
      (rs10835638, c.-211G > T) and follicle stimulating hormone receptor (FSHR)
      (rs1394205, c.-29G > A; rs6165, c.919A > G; rs6166, c.2039 A > G) genes might
      disturb normal spermatogenesis and affect male reproductive ability. METHODS: To
      further ascertain the aforementioned effects, we conducted a case-control study
      of 255 infertile men and 340 fertile controls from South China using the Mass
      ARRAY method, which was analyzed by the t-tests and logistic regression analysis
      using SPSS for Windows 14.0. In addition, a meta-analysis was performed by
      combining our results with previous reports using STATA 12.0. RESULTS: In the
      FSHB or FSHR gene single nucleotide polymorphism (SNP) evaluation, no
      statistically-significant difference was found in the frequency of allelic
      variants or in genotype distribution between cases and controls. However, a
      significant association for the comparison of GAA (P: 0.022, OR: 0.63, 95%CI:
      0.43-0.94) was seen between the oligozoospermia and controls in haplotype
      analysis of rs1394205/rs6165/rs6166. In the meta-analysis, rs6165G allele and
      rs6166 GG genotype were associated with increased risk of the male infertility.
      CONCLUSIONS: This study suggested that FSHR GAA haplotype would exert protective
      effects against male sterility, which indicated that the combination of three SNP
      genotypes of FSHR was predicted to have a much stronger impact than either one
      alone. Then in the meta-analysis, a significant association was seen between FSHR
      rs6165, rs6166 polymorphisms and male infertility. In terms of male infertility
      with multifactorial etiology, further studies with larger sample sizes and
      different ethnic backgrounds or other risk factors are warranted to clarify the
      potential role of FSHB and FSHR polymorphisms in the pathogenesis of male
      infertility.

PMID- 28764643
TI  - Detection of articular perforations of the proximal humerus fracture using a
      mobile 3D image intensifier - a cadaver study.
AB  - BACKGROUND: The purpose of this study was to investigate the accuracy of
      perforation detection with multiplanar reconstructions using a mobile 3D image
      intensifier. METHODS: In 12 paired human humeri, K-wires perforating the
      subchondral bone and placed just below the cartilage level were directed toward
      five specific regions in the humeral head. Image acquisition was initiated by a
      fluoroscopy scan. Within a range of 90 degrees , 45 degrees  external rotation
      (ER) and 45 degrees  internal rotation (IR). The number and percentage of
      detected perforating screws were grouped and analyzed. Furthermore, the
      fluoroscopic images were converted into multiplanar CT-like reconstructions. Each
      K-wire perforation was characterized as "detected" or "not detected". RESULTS: In
      the series of fluoroscopy images in the standard neutral position at 30 degrees 
      internal rotation, and 30 degrees  external rotation, the perforations of all K
      wires (n = 56) were detected. Twenty-nine (51.8%) of them were detected in one AP
      view, 22 (39.3%) in two AP views, and five (8.9%) in three AP views. All K-wire
      perforations (100%, n = 56) were detected in multiplanar reconstructions.
      CONCLUSION: In order to reveal all of the intraoperative and postoperative screw
      perforations in a "five screw configuration", conventional AP images should be
      established in both the neutral positions (0 degrees ), at 30 degrees  internal
      rotation and 30 degrees  external rotation. Alternatively, the intraoperative 3D
      scan with multiplanar reconstructions enables a 100% rate of detection of the
      screw perforations.

PMID- 28764644
TI  - Variable selection for disease progression models: methods for oncogenetic trees
      and application to cancer and HIV.
AB  - BACKGROUND: Disease progression models are important for understanding the
      critical steps during the development of diseases. The models are imbedded in a
      statistical framework to deal with random variations due to biology and the
      sampling process when observing only a finite population. Conditional
      probabilities are used to describe dependencies between events that characterise
      the critical steps in the disease process. Many different model classes have been
      proposed in the literature, from simple path models to complex Bayesian networks.
      A popular and easy to understand but yet flexible model class are oncogenetic
      trees. These have been applied to describe the accumulation of genetic
      aberrations in cancer and HIV data. However, the number of potentially relevant
      aberrations is often by far larger than the maximal number of events that can be
      used for reliably estimating the progression models. Still, there are only a few
      approaches to variable selection, which have not yet been investigated in detail.
      RESULTS: We fill this gap and propose specifically for oncogenetic trees ten
      variable selection methods, some of these being completely new. We compare them
      in an extensive simulation study and on real data from cancer and HIV. It turns
      out that the preselection of events by clique identification algorithms performs
      best. Here, events are selected if they belong to the largest or the maximum
      weight subgraph in which all pairs of vertices are connected. CONCLUSIONS: The
      variable selection method of identifying cliques finds both the important
      frequent events and those related to disease pathways.

PMID- 28764645
TI  - Correcting nucleotide-specific biases in high-throughput sequencing data.
AB  - BACKGROUND: High-throughput sequence (HTS) data exhibit position-specific
      nucleotide biases that obscure the intended signal and reduce the effectiveness
      of these data for downstream analyses. These biases are particularly evident in
      HTS assays for identifying regulatory regions in DNA (DNase-seq, ChIP-seq, FAIRE
      seq, ATAC-seq). Biases may result from many experiment-specific factors,
      including selectivity of DNA restriction enzymes and fragmentation method, as
      well as sequencing technology-specific factors, such as choice of
      adapters/primers and sample amplification methods. RESULTS: We present a novel
      method to detect and correct position-specific nucleotide biases in HTS short
      read data. Our method calculates read-specific weights based on aligned reads to
      correct the over- or underrepresentation of position-specific nucleotide
      subsequences, both within and adjacent to the aligned read, relative to a
      baseline calculated in assay-specific enriched regions. Using HTS data from a
      variety of ChIP-seq, DNase-seq, FAIRE-seq, and ATAC-seq experiments, we show that
      our weight-adjusted reads reduce the position-specific nucleotide imbalance
      across reads and improve the utility of these data for downstream analyses,
      including identification and characterization of open chromatin peaks and
      transcription-factor binding sites. CONCLUSIONS: A general-purpose method to
      characterize and correct position-specific nucleotide sequence biases fills the
      need to recognize and deal with, in a systematic manner, binding-site preference
      for the growing number of HTS-based epigenetic assays. As the breadth and impact
      of these biases are better understood, the availability of a standard toolkit to
      correct them will be important.

PMID- 28764646
TI  - A randomized double-blind, placebo-controlled trial of ganaxolone in children and
      adolescents with fragile X syndrome.
AB  - BACKGROUND: Gamma-aminobutyric acid (GABA) system deficits are integral to the
      pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABAA
      receptor positive allosteric modulator, is hypothesized to improve symptoms such
      as anxiety, hyperactivity, and attention deficits in children with FXS. METHODS:
      This study was a randomized, double-blind, placebo-controlled, crossover trial of
      ganaxolone in children with FXS, aged 6-17 years. RESULTS: Sixty-one participants
      were assessed for eligibility, and 59 were randomized to the study. Fifty-five
      participants completed at least the first arm and were included in the intention
      to-treat analysis; 51 participants completed both treatment arms. There were no
      statistically significant improvements observed on the primary outcome measure
      (Clinical Global Impression-Improvement), the key secondary outcome measure
      (Pediatric Anxiety Rating Scale-R), or any other secondary outcome measures in
      the overall study population. However, post-hoc analyses revealed positive trends
      in areas of anxiety, attention, and hyperactivity in participants with higher
      baseline anxiety and low full-scale IQ scores. No serious adverse events (AEs)
      occurred, although there was a significant increase in the frequency and severity
      of AEs related to ganaxolone compared to placebo. CONCLUSIONS: While ganaxolone
      was found to be safe, there were no significant improvements in the outcome
      measures in the overall study population. However, ganaxolone in subgroups of
      children with FXS, including those with higher anxiety or lower cognitive
      abilities, might have beneficial effects. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01725152.

PMID- 28764647
TI  - Relationship between oral health and Fried's frailty criteria in community
      dwelling older persons.
AB  - BACKGROUND: Oral health and frailty might be linked through several pathways, but
      previous studies are scarce. This study examined the association between oral
      health and components of Fried's frailty phenotype. METHODS: This cross-sectional
      analysis was based on a sample of 992 community-dwelling persons aged 73 to 77
      years observed in the 2011 follow-up of the Lausanne 65+ cohort (Lc65+) study.
      Data were collected through annual mailed questionnaires, interview and physical
      examination. Oral health was assessed according to self-reported oral pain and
      masticatory ability. Frailty was defined as meeting at least one criterion of the
      Fried's phenotype. RESULTS: Oral pain was reported by 14.8% and chewing problems
      by 9.7%. Impaired masticatory ability (IMA) was more frequent in subjects with
      missing teeth or removable dentures (13.5%) than among those with full dentition
      or fixed dental prostheses (3.2%). In logistic regression analyses adjusting for
      demographics, alcohol consumption, smoking, comorbidity and financial
      difficulties, persons with oral pain and those with chewing problems had
      significantly higher odds of being frail (adjusted ORpain = 1.72; 95% CI 1.17
      2.53 and adjORIMA1.70; 1.07-2.72, respectively). Lack of endurance was associated
      with both oral pain (adjOR = 3.61; 1.92-6.76) and impaired masticatory ability
      (adjOR = 2.20; 1.03-4.72). The latter was additionally linked to low physical
      activity (adjOR = 2.35; 1.29-4.28) and low gait speed (adjOR = 3.12; 1.41-6.90),
      whereas oral pain was associated with weight loss (adjOR = 1.80; 1.09-2.96) and
      low handgrip strength (adjOR = 1.80; 1.17-2.77). CONCLUSION: Self-reported oral
      pain and chewing impairment had a significant relation with frailty and its
      components, not only through a nutritional pathway of involuntary weight loss.
      Longitudinal analyses are needed to examine whether a poor oral condition might
      be a risk factor for the onset of frailty.

PMID- 28764648
TI  - Association mapping of starch chain length distribution and amylose content in
      pea (Pisum sativum L.) using carbohydrate metabolism candidate genes.
AB  - BACKGROUND: Although starch consists of large macromolecules composed of glucose
      units linked by alpha-1,4-glycosidic linkages with alpha-1,6-glycosidic
      branchpoints, variation in starch structural and functional properties is found
      both within and between species. Interest in starch genetics is based on the
      importance of starch in food and industrial processes, with the potential of
      genetics to provide novel starches. The starch metabolic pathway is complex but
      has been characterized in diverse plant species, including pea. RESULTS: To
      understand how allelic variation in the pea starch metabolic pathway affects
      starch structure and percent amylose, partial sequences of 25 candidate genes
      were characterized for polymorphisms using a panel of 92 diverse pea lines.
      Variation in the percent amylose composition of extracted seed starch and
      (amylopectin) chain length distribution, one measure of starch structure, were
      characterized for these lines. Association mapping was undertaken to identify
      polymorphisms associated with the variation in starch chain length distribution
      and percent amylose, using a mixed linear model that incorporated population
      structure and kinship. Associations were found for polymorphisms in seven
      candidate genes plus Mendel's r locus (which conditions the round versus wrinkled
      seed phenotype). The genes with associated polymorphisms are involved in the
      substrate supply, chain elongation and branching stages of the pea carbohydrate
      and starch metabolic pathways. CONCLUSIONS: The association of polymorphisms in
      carbohydrate and starch metabolic genes with variation in amylopectin chain
      length distribution and percent amylose may help to guide manipulation of pea
      seed starch structural and functional properties through plant breeding.

PMID- 28764649
TI  - Genetic structure and relationships within and between cultivated and wild
      korarima [Aframomum corrorima (Braun) P.C.M. Jansen] in Ethiopia as revealed by
      simple sequence repeat (SSR) markers.
AB  - BACKGROUND: Korarima [Aframomum corrorima (Braun) P.C.M. Jansen] is a spice crop
      native to Ethiopia. Understanding the extent and partitioning of diversity within
      and among crop landraces and their wild relatives is among the first steps in
      conserving and measuring their genetic potential. The present study is aimed at
      characterizing the population genetic structure and relationships between
      cultivated and wild korarima in the southwestern part of Ethiopia. RESULTS: We
      analyzed a total of 195 individuals representing seven wild and fourteen
      cultivated populations. Eleven polymorphic simple sequence repeat (SSR) markers
      were used. We observed a total of 53 alleles across the eleven loci and
      individuals. In total, 32 alleles were detected in the cultivated populations,
      whereas 49 alleles were detected in the wild populations. We found higher genetic
      diversity in wild populations than in the cultivated counterpart. This result
      implies the potential of wild korarima as a possible source for novel alleles
      contributing to the improvement of cultivated korarima. Analysis of molecular
      variance (AMOVA) showed significant but low differentiation between cultivated
      and wild korarima populations. Similarly, neighbour-joining and STRUCTURE
      analyses did not group cultivated and wild populations into two distinct
      clusters. The lack of clear differentiation between cultivated and wild
      populations could be explained by historical and contemporary gene flow between
      the two gene pools. CONCLUSION: The 11 SSR loci developed in this study could be
      employed to examine genetic diversity and population structure of korarima in
      other countries as well as other Aframomum species. From the five administrative
      zones considered in this study, the Bench-Magi and Sheka zone showed populations
      with high genetic diversity, and these populations could be used as a potential
      starting point for in-situ and ex-situ germplasm conservation and korarima
      improvement through breeding programs after proper agronomic evaluation.

PMID- 28764650
TI  - Immunocytochemistry and fluorescence imaging efficiently identify individual
      neurons with CRISPR/Cas9-mediated gene disruption in primary cortical cultures.
AB  - BACKGROUND: CRISPR/Cas9 system is a powerful method to investigate the role of
      genes by introducing a mutation selectively and efficiently to specific genome
      positions in cell and animal lines. However, in primary neuron cultures, this
      method is affected by the issue that the effectiveness of CRISPR/Cas9 is
      different in each neuron. Here, we report an easy, quick and reliable method to
      identify mutants induced by the CRISPR/Cas9 system at a single neuron level,
      using immunocytochemistry (ICC) and fluorescence imaging. RESULTS: Dissociated
      cortical cells were transfected with CRISPR/Cas9 plasmids targeting the
      transcription factor cAMP-response element binding protein (CREB). Fluorescence
      ICC with CREB antibody and quantitative analysis of fluorescence intensity
      demonstrated that CREB expression disappeared in a fraction of the transfected
      neurons. The downstream FOS expression was also decreased in accordance with
      suppressed CREB expression. Moreover, dendritic arborization was decreased in the
      transfected neurons which lacked CREB immunoreactivity. CONCLUSIONS: Detection of
      protein expression is efficient to identify individual postmitotic neurons with
      CRISPR/Cas9-mediated gene disruption in primary cortical cultures. The present
      method composed of CRISPR/Cas9 system, ICC and fluorescence imaging is applicable
      to study the function of various genes at a single-neuron level.

PMID- 28764651
TI  - Comparison of procalcitonin and high-sensitivity C-reactive protein for the
      diagnosis of sepsis and septic shock in the oldest old patients.
AB  - BACKGROUND: Although the role of serum procalcitonin (PCT) and high-sensitivity C
      reactive protein (hs-CRP) in the diagnosis of sepsis and septic shock is well
      studied, it has not been investigated among oldest old patients. The aim of our
      study is to determine the role of PCT and hs-CRP in the assessment of sepsis and
      septic shock in this specific group of patients in the ICU. METHODS: This is a
      prospective observational study. Patients >85 years of age admitted to the ICU
      from May 1st, 2016 to February 1st, 2017 were evaluated. Patients were divided
      into a sepsis and septic shock group(sepsis/SS) and a non-sepsis group. Serum
      levels of PCT, hs-CRP and the WBC were measured within 12 h of admission.
      RESULTS: A total of 70 patients aged 85 years and older were enrolled in this
      study. Fifty patients were labelled as sepsis/SS and the other 20 were labelled
      non-sepsis. A ROC analysis showed that the area under the curves (AUC) of hs-CRP
      and PCT for the discrimination of sepsis/SS patients were 0.825 (95% confidence
      interval[CI]: 0.73-0.92; P < 0.001) and 0.819 (95%CI:0.72-0.92; p < 0.001),
      respectively. In a subgroup analysis of the sepsis/SS group, 27 patients had
      sepsis, while the other 23 patients had septic shock. The ROC analysis showed
      that the AUCs of hs-CRP and PCT for the discrimination of septic shock patients
      from sepsis patients were 0.751 (95% CI: 0.62-0.88; P = 0.002) and 0.719 (95%
      CI:0.57-0.86; p = 0.007), respectively. CONCLUSION: For the oldest old patients,
      hs-CRP is not inferior to PCT in the diagnosis of sepsis and septic shock.

PMID- 28764652
TI  - Tissue sublimation follow transarterial embolization of a follicular nodular
      hyperplasia of the liver-report of a case.
AB  - BACKGROUND: Follicular nodular hyperplasia (FNH) is a common benign liver tumor
      for which conservative management is indicated. Surgical or interventional
      management is indicated in symptomatic cases. Transarterial embolization (TAE)
      has been extensively used to manage unresectable liver tumors. Sublimation
      describes a change of physical state from solid to gas. Hepatic tissue
      sublimation following TAE has so far not been reported in medical literature.
      CASE PRESENTATION: A 30 year - old male patient presenting with pain to the upper
      abdomen due to a large FNH was managed with TAE. Routine radiographic control on
      post-intervention day one was within normal limits. Imaging due to right upper
      quadrant pain with fever and elevated inflammatory markers and liver enzymes on
      day two after TAE revealed a marked reduction of the FNH accompanied by the
      presence of a large volume of gas collection without signs of abscess formation.
      This change of state from solid to gas without sign of abscess formation within 2
      days after TAE was described as hepatic tissue sublimation. The patient was
      managed conservatively and discharge 12 days after TAE. CONCLUSION: Tissue
      sublimation has hardly been reported in medical literature. This to the best of
      our knowledge is the first documented case of hepatic tissue sublimation
      following TAE.

PMID- 28764653
TI  - Maize network analysis revealed gene modules involved in development, nutrients
      utilization, metabolism, and stress response.
AB  - BACKGROUND: The advent of big data in biology offers opportunities while poses
      challenges to derive biological insights. For maize, a large amount of publicly
      available transcriptome datasets have been generated but a comprehensive analysis
      is lacking. RESULTS: We constructed a maize gene co-expression network based on
      the graphical Gaussian model, using massive RNA-seq data. The network, containing
      20,269 genes, assembles into 964 gene modules that function in a variety of plant
      processes, such as cell organization, the development of inflorescences, ligules
      and kernels, the uptake and utilization of nutrients (e.g. nitrogen and
      phosphate), the metabolism of benzoxazionids, oxylipins, flavonoids, and wax, and
      the response to stresses. Among them, the inflorescences development module is
      enriched with domestication genes (like ra1, ba1, gt1, tb1, tga1) that control
      plant architecture and kernel structure, while multiple other modules relate to
      diverse agronomic traits. Contained within these modules are transcription
      factors acting as known or potential expression regulators for the genes within
      the same modules, suggesting them as candidate regulators for related biological
      processes. A comparison with an established Arabidopsis network revealed
      conserved gene association patterns for specific modules involved in cell
      organization, nutrients uptake & utilization, and metabolism. The analysis also
      identified significant divergences between the two species for modules that
      orchestrate developmental pathways. CONCLUSIONS: This network sheds light on how
      gene modules are organized between different species in the context of
      evolutionary divergence and highlights modules whose structure and gene content
      can provide important resources for maize gene functional studies with
      application potential.

PMID- 28764654
TI  - Association of restless legs syndrome and mortality in end-stage renal disease:
      an analysis of the United States Renal Data System (USRDS).
AB  - BACKGROUND: Objective of the study is to assess prevalence and survival among end
      stage renal disease patients with restless legs syndrome (RLS) within a national
      database (USRDS). METHODS: A case-control, retrospective analysis was performed.
      Differences in characteristics between the groups, RLS and those with no sleep
      disorder (NSD), were determined using chi2 tests. Cox proportional hazard
      regression was used to assess survival between those with RLS and propensity
      score matched controls. RESULTS: Cases of restless legs syndrome were defined as
      patients that had received an ICD-9 code of 333.94 at any point during their
      treatment (n = 372). RLS group demonstrated a significantly higher proportion of
      patients with major depressive disorder, dysthymic disorder, anxiety, depression,
      minor depressive disorder, and psychological disorder. The difference between the
      survival was not statistically significant in those without sleep disorder as
      compared to those with RLS (HR =1.16+/-0.14, p = 0.3). CONCLUSIONS: True
      prevalence of RLS in dialysis patients can only be estimated if knowledge gap for
      care providers in diagnosis of RLS is addressed. RLS patients also have increased
      incidence of certain psychological disorders which needs to be addressed.

PMID- 28764655
TI  - A case report: primary amoebic meningoencephalitis in a young Zambian adult.
AB  - BACKGROUND: Primary amoebic meningoencephalitis (PAM) is a fulminant disease of
      the brain caused by Naegleria fowleri. Although the disease is rare, the case
      fatality rate is very high. In this report, we describe the first case of PAM in
      Zambia. CASE PRESENTATION: The patient presented with sudden onset of seizures
      and fever on admission. On physical examination he was febrile, comatose and with
      a stiff neck. Cerebral spinal fluid (CSF) collected on admission did not reveal
      any organism on microscopy or culture but showed elevated white cell count. A
      working diagnosis of severe septicemia with acute meningoencephalitis was then
      made and the patient was started on IV Cephtriaxone (2 g) twice daily. Despite
      receiving treatment, his condition deteriorated. A second CSF sample collected on
      day 3 was also negative for bacteria and other organisms. However, a repeat CSF
      sample collected on day 8 revealed numerous motile organisms that were identified
      as Naegleria on microscopy and confirmed to be N. fowleri on polymerase chain
      reaction. The patient died on day 8 of hospital admission after having received
      one dose of Amphotericin B (50 mg). Features consistent with PAM were detected on
      autopsy. CONCLUSION: The isolation of N. fowleri in this patient calls for
      increased awareness among clinical and laboratory staff on suspected PAM cases to
      promptly diagnose and effectively manage the disease.

PMID- 28764656
TI  - Relationship between serum uric acid level and mild cognitive impairment in
      Chinese community elderly.
AB  - BACKGROUND: To evaluate the association between SUA levels within a normal to
      high range and the risk of mild cognitive impairment (MCI) among community
      elderly. METHODS: The present study was based on 2102 community elderly from a
      cross-sectional study conducted in a representative urban area of Beijing between
      2009 and 2010. The mean age were 71.2 +/- 6.6 years old, 59.7% were female. Mini
      Mental State Examination (MMSE) was used to assess cognitive function by trained
      neurology doctors. RESULTS: The prevalence of hyperuricemia and MCI was 16.7% and
      15.9% respectively. With the increase of SUA levels, the prevalence of MCI showed
      a strong decreasing linear trend. Multiple logistic regression analysis showed
      ORs for MCI were 1.01(95% CI: 0.69-1.48), 1.50(95% CI: 0.85-2.64), 1.65(95% CI:
      1.12-2.43) and 1.53(95% CI: 1.00-2.33), 1.84(95% CI: 1.27-2.90), 1.92(95% CI:
      1.02-3.35) for the second, third and highest quarters among men and women
      respectively (with the lowest quartile as the reference). CONCLUSIONS: Higher SUA
      levels, when in the normal range, were positively associated with cognitive
      function among Chinese community elderly, but this association was not robust
      among participants with hyperuricemia.

PMID- 28764657
TI  - Hepatic iron overload is associated with hepatocyte apoptosis during Clonorchis
      sinensis infection.
AB  - BACKGROUND: Hepatic iron overload has been implicated in many liver diseases;
      however, whether it is involved in clonorchiasis remains unknown. The purpose of
      this study is to investigate whether Clonorchis sinensis (C. sinensis) infection
      causes hepatic iron overload, analyze the relationship between the iron overload
      and associated cell apoptosis, so as to determine the role of excess iron plays
      in C. sinensis-induced liver injury. METHODS: The Perls' Prussian staining and
      atomic absorption spectrometry methods were used to investigate the iron overload
      in hepatic sections of wistar rats and patients infected with C. sinensis. The
      hepatic apoptosis was detected by transferase uridyl nick end labeling (TUNEL)
      methods. Spearman analysis was used for determining the correlation of the
      histological hepatic iron index and the apoptotic index. RESULTS: Blue iron
      particles were deposited mainly in the hepatocytes, Kupffer cells and endothelial
      cells, around the liver portal and central vein area of both patients and rats.
      The total iron score was found to be higher in the infected groups than the
      respective control from 8 weeks. The hepatic iron concentration was also
      significantly higher in treatment groups than in control rats from 8 weeks. The
      hepatocyte apoptosis was found to be significantly higher in the portal area of
      the liver tissue and around the central vein. However, spearman's rank
      correlation coefficient revealed that there was a mildly negative correlation
      between the iron index and hepatocyte apoptosis. CONCLUSIONS: This present study
      confirmed that hepatic iron overload was found during C. sinensis infection. This
      suggests that iron overload may be associated with hepatocyte apoptosis and
      involved in liver injury during C. sinensis infection. Further studies are needed
      to investigate the molecular mechanism involved here.

PMID- 28764658
TI  - Comparative genomic and phylogenomic analyses of the Bifidobacteriaceae family.
AB  - BACKGROUND: Members of the Bifidobacteriaceae family represent both dominant
      microbial groups that colonize the gut of various animals, especially during the
      suckling stage of their life, while they also occur as pathogenic bacteria of the
      urogenital tract. The pan-genome of the genus Bifidobacterium has been explored
      in detail in recent years, though genomics of the Bifidobacteriaceae family has
      not yet received much attention. Here, a comparative genomic analyses of 67
      Bifidobacteriaceae (sub) species including all currently recognized genera of
      this family, i.e., Aeriscardovia, Alloscardovia, Bifidobacterium, Bombiscardovia,
      Gardnerella, Neoscardovia, Parascardovia, Pseudoscardovia and Scardovia, was
      performed. Furthermore, in order to include a representative of each of the 67
      (currently recognized) (sub) species belonging to the Bifidobacteriaceae family,
      we sequenced the genomes of an additional 11 species from this family,
      accomplishing the most extensive comparative genomic analysis performed within
      this family so far. RESULTS: Phylogenomics-based analyses revealed the deduced
      evolutionary pathway followed by each member of the Bifidobacteriaceae family,
      highlighting Aeriscardovia aeriphila LMG 21773 as the deepest branch in the
      evolutionary tree of this family. Furthermore, functional analyses based on
      genome content unveil connections between a given member of the family, its
      carbohydrate utilization abilities and its corresponding host. In this context,
      bifidobacterial (sub) species isolated from humans and monkeys possess the
      highest relative number of acquired glycosyl hydrolase-encoding genes, probably
      in order to enhance their metabolic ability to utilize different carbon sources
      consumed by the host. CONCLUSIONS: Within the Bifidobacteriaceae family, genomics
      of the genus Bifidobacterium has been extensively investigated. In contrast, very
      little is known about the genomics of members of the other eight genera of this
      family. In this study, we decoded the genome sequences of each member of the
      Bifidobacteriaceae family. Thanks to subsequent comparative genomic and
      phylogenetic analyses, the deduced pan-genome of this family, as well as the
      predicted evolutionary development of each taxon belonging to this family was
      assessed.

PMID- 28764659
TI  - Non-steroidal anti-inflammatory drug induced acute kidney injury in the community
      dwelling general population and people with chronic kidney disease: systematic
      review and meta-analysis.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are a common cause of
      adverse drug events (ADEs), but renal risks of NSAIDs are less well quantified
      than gastrointestinal and cardiac risks. This paper reports a systematic review
      of published population-based observational studies examining the risk of acute
      kidney injury (AKI) associated with NSAIDs in community-dwelling adults and those
      with pre-existing chronic kidney disease (CKD). METHODS: MEDLINE and EMBASE
      databases were searched until June 2016, and 3789 papers screened. Ten studies
      reporting NSAID risk of AKI in the general population were included in random
      effects meta-analysis, of which five additionally reported NSAID risk in people
      with CKD. RESULTS: In the general population, the pooled odds ratio (OR) of AKI
      for current NSAID exposure was 1.73 (95%CI 1.44 to 2.07), with somewhat higher
      risk observed in older people (OR 2.51, 95%CI 1.52 to 2.68). In people with CKD,
      individual study OR of AKI due to current NSAID exposure ranged from 1.12 to
      5.25, with pooled estimate OR 1.63 (95% CI 1.22 to 2.19). CONCLUSIONS: No study
      reported baseline risk of AKI in different populations meaning absolute risks
      could not be estimated, but baseline risk and therefore the absolute risk of
      NSAID exposure is likely to be higher in people with CKD and older people. Large
      population based studies measuring AKI using current definitions and estimating
      the absolute risk of harm are needed in order to better inform clinical decision
      making.

PMID- 28764660
TI  - Relationship between day 1 and day 2 Vancomycin area under the curve values and
      emergence of heterogeneous Vancomycin-intermediate Staphylococcus aureus (hVISA)
      by Etest(r) macromethod among patients with MRSA bloodstream infections: a pilot
      study.
AB  - BACKGROUND: In vitro data suggests that suboptimal initial vancomycin exposure
      may select for heterogeneous vancomycin-intermediate Staphylococcus aureus
      (hVISA) infections. However, no clinical studies have evaluated the relationship
      between initial vancomycin exposure and emergence of hVISA. This pilot study
      seeks to assess the relationship between day 1 and day 2 vancomycin area under
      the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest(r)
      macromethod among patients with a non-hVISA BSI at baseline. METHODS: This was a
      retrospective cohort study of patients with methicillin-resistant Staphylococcus
      aureus (MRSA) BSIs at Albany Medical Center Hospital (AMCH) between January 2005
      and June 2009. The vancomycin AUC exposure variables on day 1 (AUC0-24h) and day
      2 (AUC24-48h) were estimated using the maximal a posteriori probability (MAP)
      procedure in ADAPT 5. RESULTS: There were 238 unique episodes of MRSA BSIs during
      the study period, 119 of which met inclusion criteria. Overall, hVISA emerged in
      7/119 (5.9%) of patients. All 7 cases of hVISA involved patients who did not
      achieve area under the curve over broth microdilution minimum inhibitory
      concentration (AUC0-24h/MICBMD) ratio of 521 or an AUC24-48h/MICBMD ratio of 650.
      No associations between other day 1 and day 2 AUC variables and emergence of
      hVISA were noted. CONCLUSIONS: Although more data are needed to draw definitive
      conclusions, these findings suggest that hVISA emergence among patients with non
      hVISA MRSA BSIs at baseline may be partially explained by suboptimal exposure to
      vancomycin in the first 1 to 2 days of therapy. At a minimum, these findings
      support further study of the relationship between initial vancomycin exposure and
      hVISA emergence among patients with MRSA BSIs in a well-powered, multi-center,
      prospective trial.

PMID- 28764662
TI  - A case report of co-infection of Melioidosis and cutaneous Leishmaniasis.
AB  - BACKGROUND: Leishmaniasis and melioidosis are frequently reported from the North
      Central Province of Sri Lanka. However, only one case of co-infection of the two
      diseases has been reported to date over the world. This is a case report of a
      patient who had co-infection with cutaneous leishmaniasis and melioidosis and was
      successfully treated and recovered from the illness. CASE PRESENTATION: A 61 year
      old female patient with diabetes mellitus presented with fever for one month's
      duration and was found to have hepatosplenomegaly and an ulcer over the left arm.
      She had elevated inflammatory markers and blood culture grew Burkholderia
      pseudomallei and serum was highly positive for melioidosis antibodies. A slit
      skin smear of the ulcer showed Leishmania amastigotes. CONCLUSION: Melioidosis
      and leishmaniasis are emerging infectious diseases in endemic countries and can
      be severe. The high prevalence rates in Sri Lanka should keep the treating
      physicians' threshold for suspicion low for these two diseases.

PMID- 28764663
TI  - Erratum to: Detection of gene-environment interactions in the presence of linkage
      disequilibrium and noise by using genetic risk scores with internal weights from
      elastic net regression.

PMID- 28764661
TI  - HIV testing week 2015: lowering barriers for HIV testing among high-risk groups
      in Amsterdam.
AB  - BACKGROUND: Evaluation of the HIV Testing Week (HTW) 2015 in Amsterdam: the
      number of (positive) tested persons, characteristics and testing history of the
      tested population, the differences in attendance per location and the healthcare
      workers' experiences and opinions concerning the HTW. METHODS: The HTW took place
      from 28 November till 4 December 2015. Anonymous HIV rapid testing (INSTITM
      HIV1/HIV2 Ab test or DetermineTM HIV-1/2 Ag/Ab test) was offered free of charge
      at four hospitals, 12 general practitioner (GP) clinics, a sexually transmitted
      infections (STI) clinic, a laboratory, sites of a community-based organisation,
      and at outreach locations. Home-based testing (OraQuick(r) In-Home HIV Test) was
      offered online. The focus was to motivate two groups to test: men who have sex
      with men (MSM) and non-Western migrants. Questionnaires regarding participant's
      characteristics and HIV testing history were collected. Also healthcare workers
      were asked to complete a questionnaire evaluating the HTW. RESULTS: In total,
      1231 participants were tested. With three positive HIV tests, the detection rate
      was 0.3% (95%CI 0.26-0.37). Of all participants, 24.7% (304/1231) were MSM.
      Respectively, 22.3% (275/1231) and 15.7% (193/1231) were first- and second
      generation migrants from a non-Western country. Altogether, 56.7% (698/1231) of
      participants belonged to one of the targeted risk groups. For 32.7% (402/1231) of
      participants, it was the first time they received testing, and 35.1% (432/1231)
      were tested more than 1 year ago. Among MSM 13.2% were tested for the first time,
      among first- and second-generation non-Western migrants this percentage was
      significantly higher at 27.2% and 33.5% respectively (p < 0.01). The number of
      tested participants per location varied widely, especially between GP clinics
      (range 3-63). Healthcare workers were positive about the HTW: about half (46.2%)
      stated they would more readily offer an HIV test following their experience with
      the HTW. CONCLUSIONS: This was the first time the Amsterdam HTW was organised on
      such a large scale. The majority of the tested population belonged to one of the
      targeted risk groups and received testing either for the first time or for the
      first time in over a year. It is important to further build upon the experiences
      of the HTW and offer free of charge low-threshold HIV testing more structurally.
      An evaluation of cost-effectiveness is also warranted for future editions of the
      HTW.

PMID- 28764664
TI  - Group demography affects ant colony performance and individual speed of queen and
      worker aging.
AB  - BACKGROUND: The performance and fitness of social societies mainly depends on the
      efficiency of interactions between reproductive individuals and helpers. Helpers
      need to react to the group's requirements and to adjust their tasks accordingly,
      while the reproductive individual has to adjust its reproductive rate. Social
      insects provide a good system to study the interrelations between individual and
      group characteristics. In general, sterile workers focus on brood care and
      foraging while the queen lays eggs. Reproductive division of labor is determined
      by caste and not interchangeable as, e.g., in social mammals or birds. Hence,
      changing social and environmental conditions require a flexible response by each
      caste. In the ant Cardiocondyla obscurior, worker task allocation is based on age
      polyethism, with young workers focusing on brood care and old workers on
      foraging. Here, we examine how group age demography affects colony performance
      and fitness in colonies consisting of only old or young workers and a single old
      or young queen. We hypothesized that both groups will be fully functional, but
      that the forced task shift affects the individuals' performance. Moreover, we
      expected reduced worker longevity in groups with only young workers due to
      precocious foraging but no effect on queen longevity depending on group
      composition. RESULTS: Neither the performance of queens nor that of workers
      declined strongly with time per se, but offspring number and weight were
      influenced by queen age and the interaction between queen and worker age.
      Individual residual life expectancy strongly depended on colony demography
      instead of physiological age. While worker age affected queen longevity only
      slightly, exposing old workers to the conditions of colony founding increased
      their life spans by up to 50% relative to workers that had emerged shortly before
      colony set-up. CONCLUSIONS: The social environment strongly affected the tempo of
      aging and senescence in C. obscurior, highlighting the plasticity of life
      expectancy in social insects. Furthermore, colonies obtained the highest
      reproductive output when consisting of same-aged queens and workers independent
      of their physiological age. However, workers appeared to be able to adjust their
      behavior to the colony's needs and not to suffer from age-dependent restrictions.

PMID- 28764665
TI  - Factors influencing timely initiation and completion of gestational diabetes
      mellitus screening and diagnosis - a qualitative study from Tamil Nadu, India.
AB  - BACKGROUND: In 2007, universal screening for gestational diabetes mellitus (GDM)
      was introduced in Tamil Nadu, India. To identify factors hindering or
      facilitating timely initiation and completion of the GDM screening and diagnosis
      process, our study investigated how pregnant women in rural and urban Tamil Nadu
      access and navigate different GDM related health services. METHODS: The study was
      carried out in two settings: an urban private diabetes centre and a rural
      government primary health centre. Observations of the process of screening and
      diagnosis at the health centres as well as semi-structured interviews with 30
      pregnant women and nine health care providers were conducted. Data was analysed
      using qualitative content analysis. RESULTS: There were significant differences
      in the process of GDM screening and diagnosis in the urban and rural settings.
      Several factors hindering or facilitating timely initiation and completion of the
      process were identified. Timely attendance required awareness, motivation and
      opportunity to attend. Women had to attend the health centre at the right time
      and sometimes at the right gestational age to initiate the test, wait to complete
      the test and obtain the test report in time to initiate further action. All these
      steps and requirements were influenced by factors within and outside the health
      system such as getting right information from health care providers, clinic
      timings, characteristics of the test, availability of transport, social network
      and support, and social norms and cultural practices. CONCLUSIONS: Minimising and
      aligning complex stepwise processes of prenatal care and GDM screening delivery
      and attention to the factors influencing it are important for further improving
      and expanding GDM screening and related services, not only in Tamil Nadu but in
      other similar low and middle income settings. This study stresses the importance
      of guidelines and diagnostic criteria which are simple and feasible on the
      ground.

PMID- 28764666
TI  - A mega-ethnography of eleven qualitative evidence syntheses exploring the
      experience of living with chronic non-malignant pain.
AB  - BACKGROUND: Each year over five million people develop chronic non-malignant pain
      and can experience healthcare as an adversarial struggle. The aims of this study
      were: (1) to bring together qualitative evidence syntheses that explore patients'
      experience of living with chronic non-malignant pain and develop conceptual
      understanding of what it is like to live with chronic non-malignant pain for
      improved healthcare; (2) to undertake the first mega-ethnography of qualitative
      evidence syntheses using the methods of meta-ethnography. METHODS: We used the
      seven stages of meta-ethnography refined for large studies. The innovation of
      mega-ethnography is to use conceptual findings from qualitative evidence
      syntheses as primary data. We searched 7 bibliographic databases from inception
      until February 2016 to identify qualitative evidence syntheses that explored
      patients' experience of living with chronic non-malignant pain. RESULTS: We
      identified 82 potential studies from 556 titles, screened 34 full text articles
      and included 11 qualitative evidence syntheses synthesising a total of 187
      qualitative studies reporting more than 5000 international participants living
      with chronic pain. We abstracted concepts into 7 conceptual categories: (1) my
      life is impoverished and confined; (2) struggling against my body to be me; (3)
      the quest for the diagnostic 'holy grail'; (4) lost personal credibility; (5)
      trying to keep up appearances; (6) need to be treated with dignity; and (7)
      deciding to end the quest for the grail is not easy. Each conceptual category was
      supported by at least 7 of the 11 qualitative evidence syntheses. CONCLUSIONS:
      This is the first mega-ethnography, or synthesis of qualitative evidence
      syntheses using the methods of meta-ethnography. Findings help us to understand
      that the decision to end the quest for a diagnosis can leave patients feeling
      vulnerable and this may contribute to the adversarial nature of the clinical
      encounter. This knowledge demonstrates that treating a patient with a sense that
      they are worthy of care and hearing their story is not an adjunct to, but
      integral to health care.

PMID- 28764667
TI  - Patterns of participation over four rounds of annual fecal immunochemical test
      based screening for colorectal cancer: what predicts rescreening?
AB  - BACKGROUND: Participation at the recommended intervals is critical for screening
      to be effective in reducing colorectal cancer (CRC) incidence. This study
      describes patterns of screening participation over four rounds of fecal
      immunochemical testing (FIT) to identify whether demographic variables and prior
      screening satisfaction are significantly associated with patterns of re
      participation. METHODS: Baseline surveys were mailed to 4000 South Australians
      randomly selected from the electoral-roll. Respondents (n = 1928/48.2%) were
      offered four annual FIT rounds. Screening participation and satisfaction at each
      round were recorded. RESULTS: Study participation was 58.5, 66.9, 73.1 and 71.4%
      respectively over four rounds. Three participation patterns were described:
      consistent participation (43.1%), consistent non-participation (26.4%) and
      inconsistent participation (changeable; 30.5%), including intermittent and
      sustained change patterns. Sustained change described those who changed
      participatory behavior and then maintained for at least two rounds (n =
      375/19.5%). Older people, and those not working were most likely to sustain
      participation. Younger invitees, especially men, were more likely to change
      participatory behavior and sustain the change. People with higher disadvantage,
      less education, not working and with no prior (pre-trial) screening experience
      were more likely to start participating and drop out. People dissatisfied with a
      prior screening test, including finding aspects embarrassing or unpleasant, were
      also more likely not to participate in annual screening or to drop out.
      CONCLUSIONS: The findings identify those at risk of non- or inconsistent
      participation in rescreening. They should aid targeting of interventions for
      demographic groups at risk and ensuring screening experiences are not perceived
      as unpleasant or difficult.

PMID- 28764668
TI  - Liquor licences issued to Australian schools.
AB  - BACKGROUND: Children's positive socialisation to alcohol is associated with early
      initiation of drinking and alcohol-related harm in adult life. Internationally,
      there have been reports of adults' alcohol consumption at school events in the
      presence of children. The aim of this research was to identify the conditions
      under which Australian schools are required to apply for a liquor licence and the
      associated prevalence of liquor licences for these events where children were
      likely to be present. METHODS: A document review was conducted to examine
      temporary liquor licensing legislation. Quantitative analysis was used to examine
      relevant licensing data. Coding criteria was developed to determine school type,
      student year levels and the likely presence of children. RESULTS: Four
      jurisdictions provided data on 1817 relevant licences. The average annual
      licences/100 schools was highest amongst Independent schools followed by Catholic
      and public (government) schools. The rates were highest in Queensland and
      Victoria where children were present at 61% and 32% of events respectively.
      CONCLUSIONS: While there are legislative differences across jurisdictions, the
      prevalence of adults' alcohol use at school events in the presence of children
      may reflect the various education department policies and principals' and school
      communities' beliefs and attitudes. Licences are not required for all events
      where liquor is consumed so the prevalence of adults' use of alcohol at school
      events is likely to be higher than our analyses imply. Such practices may
      undermine teaching about alcohol use in the school curriculum and health
      promotion efforts to develop alcohol-free events when children are present.

PMID- 28764669
TI  - Determinants of childhood stunting in the Democratic Republic of Congo: further
      analysis of Demographic and Health Survey 2013-14.
AB  - BACKGROUND: Prevalence of child stunting in the Democratic Republic of Congo
      (DRC) is among the highest in the world. There is a need to systematically
      investigate how stunting operates at different levels of determination and
      identify major factors contributing to the development of stunting. The aim of
      this study was to look for key determinants of stunting in the DRC. METHODS: This
      study used data from the DRC Demographic Health Survey 2013-14 which included
      anthropometric measurement for 9030 under 5 year children. Height-for-Age Z score
      was calculated and classified according to the WHO guideline. The association
      between stunting and bio-demographic characteristics was assessed using logistic
      regression. RESULTS: Prevalence of stunting was much higher in boys than girls.
      There was a significant rural urban gap in the prevalence of stunting with rural
      areas having a larger proportion of children living with stunting than urban.
      Male children, older than 6 months, preceding birth interval less than 24 months,
      being from lower wealth quintiles had the highest odds of stunting. Several
      provinces had in particular high odds of stunting. Early initiation of
      breastfeeding, mother's age more than 20 years at the time of delivery had lower
      odds of stunting. The taller the mother the less likely the child was to be
      stunted. Similarly, mother's BMI, access to safe water, access to hygienic
      toilet, mother's education were found negatively correlated with child stunting
      in the bivariate logistic regression, but they lost statistical significance in
      multivariate analysis together with numbers of children in the family and place
      of residence. CONCLUSIONS: Child stunting is widespread in the DRC and increasing
      prevalence is worrisome. This study has identified modifiable factors determining
      high prevalence of stunting in the DRC. Policy implementation should in
      particular target provinces with high prevalence of stunting and address
      modifiable determinants such as reducing socioeconomic disparity. Nutrition
      promotion intervention, including early initiation of breastfeeding should be an
      immediate priority.

PMID- 28764670
TI  - Determinants of contraceptive use and future contraceptive intentions of women
      attending child welfare clinics in urban Ghana.
AB  - BACKGROUND: Family planning is an integral component of maternal and child health
      services in Ghana. Although knowledge on contraception is universal and most
      women attend maternal and child health services, contraceptive use remains low
      among women after delivery. This study aimed to determine factors influencing
      current use and future contraceptive intentions of women who were attending child
      welfare clinics within 2 years of delivery in Sunyani Municipality, Ghana.
      METHODS: We conducted an analytical cross-sectional study among mothers in six
      selected health care facilities. Data was collected on their socio-demographic
      characteristics, reproductive and contraceptive experiences and future
      contraceptive intentions. Categorical variables were compared using the chi
      squared (chi2) test. Factors associated with current use and future contraceptive
      intentions were determined using Poisson regression with a robust error variance
      to estimate crude and adjusted relative risks (RRs) with 95% confidence intervals
      (CIs). P < 0.1 was considered statistically significant. RESULTS: A total of 590
      women were recruited into the study. Overall, 50.2% of the women were using
      contraception, 30.7% modern and 19.5% traditional methods. Compared to previous
      use, more women were using and would prefer the more effective contraceptive
      methods in future. Significant factors associated with current contraceptive use
      were, level of education (p = 0.02), discussing family planning during antenatal
      care (adjusted RR, 1.28; 95% CI, 1.07-1.53), or with one's partner (adjusted RR,
      1.22; 95% CI, 1.01-1.47) and previous contraceptive use (adjusted RR, 1.91; 95%
      CI, 1.56-2.33). Family planning discussions during child welfare clinic (adjusted
      RR, 1.12; 95% CI, 0.99-1.26) or with one's spouse (adjusted RR, 1.20; 95% CI,
      1.08-1.34), desire to space children (adjusted RR, 1.35; 95% CI, 1.17-1.55),
      previous (adjusted RR, 1.15; 95% CI, 1.05-1.27) and current (adjusted RR, 1.11;
      95% CI, 1.01-1.22) contraceptive use were predictive of clients' intention to
      adopt family planning in the future. CONCLUSION: Effective counselling on family
      planning during antenatal and child welfare clinics, and encouraging spousal
      communication on contraception are likely to increase contraceptive use after
      delivery.

PMID- 28764671
TI  - Retinoids, anxiety and peripartum depressive symptoms among Chinese women: a
      prospective cohort study.
AB  - BACKGROUND: The current study aimed to investigate whether serum RBP levels can
      be a key predictor of peripartum depression (PPD). METHODS: This was a
      prospective cohort study, conducted at a general teaching hospital in South
      China. Research participants were evaluated at three time points: the third
      trimester of pregnancy (T1), after delivery at week one (T2), and after delivery
      week six (T3) using a set of self-reported questionnaires and blood sample
      assays. RESULTS: A total of 156 subjects were included for data analysis. The
      prevalence of anxiety symptoms ranged from 32.69% to 36.53%. The prevalence of
      PPD was also high and ranged from 27.56% to 35.89%. In the third trimester,
      significant predictors of depressive symptoms include serum retinol-binding
      protein (RBP) concentrations and estradiol levels (P = 0.008 and 0.033,
      respectively). At one week after delivery, serum concentrations of RBP at T2 were
      still significant predictors of depressive symptoms (P = 0.020, and serum
      estradiol concentrations at T1 were a significant predictor (P = 0.010). The most
      stable predictor of depressive symptoms at T3 was anxiety symptoms, especially at
      T3 time point (P < 0.001). Serum RBP concentrations at T1 and T2 were still
      significant predictors of depressive symptoms at T3. CONCLUSION: A high
      prevalence of anxiety and depressive symptoms tended to persist in Chinese women
      during the peripartum period. This study, which found the potential contribution
      of RBP to the occurrence of PPD, requires that large sample studies be conducted
      in future with a longer-term follow-up period, in order to confirm its results.

PMID- 28764672
TI  - Seeking to understand lived experiences of personal recovery in personality
      disorder in community and forensic settings - a qualitative methods
      investigation.
AB  - BACKGROUND: Understandings of personal recovery have emerged as an alternative
      framework to traditional ideas of clinical progression, or symptom remission, in
      clinical practice. Most research in this field has focussed on the experience of
      individuals suffering with psychotic disorders and little research has been
      conducted to explore the experience of individuals with a personality disorder
      diagnosis, despite the high prevalence of such difficulties. The nature of the
      personality disorder diagnosis, together with high prevalence rates in forensic
      settings, renders the understanding of recovery in these contexts particularly
      problematic. The current study seeks to map out pertinent themes relating to the
      recovery process in personality disorder as described by individuals accessing
      care in either community or forensic settings. METHODS: Individual qualitative
      interviews were utilised to explore the lived experience of those receiving a
      personality disorder diagnosis and accessing mental health care in either
      community or forensic settings. A thematic analysis was conducted to identify
      shared concepts and understanding between participants. RESULTS: Fourty-one
      individual participant interviews were conducted across forensic and community
      settings. Recovery was presented by participants as a developing negotiated
      understanding of the self, together with looked for change and hope in the
      future. Four specific themes emerged in relation to this process: 1.
      Understanding early lived experience as informing sense of self 2. Developing
      emotional control 3. Diagnosis as linking understanding and hope for change 4.
      The role of mental health services. CONCLUSIONS: Through considering personal
      recovery in personality disorder as a negotiated understanding between the
      individual, their social networks and professionals this study illustrates the
      complexity of working through such a process. Clarity of understanding in this
      area is essential to avoid developing resistance in the recovery process.
      Understanding of recovery in a variety of diagnostic categories and social
      settings is essential if a truly recovery orientated mental health service is to
      be developed.

PMID- 28764673
TI  - Exploring coronial determination of intent for poisoning-related deaths in
      Australia, 2001-2013.
AB  - BACKGROUND: In countries like the United States and the United Kingdom,
      systematic variation in the classification of intent in pharmaceutical poisoning
      deaths have been identified between jurisdictions. This study aimed to explore
      whether the coronial determination of intent (unintentional, intentional,
      undetermined) for pharmaceutical-related poisoning deaths may have affected death
      rates over time and by jurisdiction in Australia. METHODS: A retrospective
      examination of mortality records in the National Coronial Information System
      (NCIS) during 1 January 2001 to 31 December 2013 was conducted. The NCIS is a
      national internet-based data storage and retrieval system for deaths that were
      notified to a coroner. Pharmaceutical deaths due to unintentional, intentional or
      undetermined intent were identified using the NCIS classification. Proportions of
      the different intent classifications and the mortality rates by intent over time
      were compared between jurisdictions. RESULTS: There were 17,895 pharmaceutical
      related poisoning deaths in Australia between 2001 and 2013 that had closed cases
      in the NCIS. Proportions of deaths classified as unintentional (48.3-66.3%),
      intentional (24.7-35.9%) and undetermined (6.7-24.7%) varied significantly among
      Australian jurisdictions. There were significant increases in the rate of
      classification of unintentional poisoning for some states, and significant
      increases in intentional poisoning classification in Western Australia, and
      decreases in New South Wales and Victoria. There was no significant change in
      classification of undetermined intent. CONCLUSIONS: Significant variation in
      classifications of intent, both between state jurisdictions and over time, may be
      the result of regional differences in demographics and increases in prescription
      drug misuse. However, the inconsistent use of 'undetermined' intent between state
      jurisdictions suggests coroners may experience varying difficulty in
      retrospectively ruling on intent in the equivocal circumstances of pharmaceutical
      poisoning. The widespread use of psychological autopsy may assist coroners to
      classify intent, while the implementation of new classifications for
      pharmaceutical poisoning death may overcome some of the inherent difficulty in
      intent classification and improve the potential for injury surveillance
      irrespective of intent.

PMID- 28764674
TI  - Arabin cervical pessary for prevention of preterm birth in cases of twin-to-twin
      transfusion syndrome treated by fetoscopic LASER coagulation: the PECEP LASER
      randomised controlled trial.
AB  - BACKGROUND: Fetoscopic LASER coagulation of the placental anastomoses has changed
      the prognosis of twin-twin transfusion syndrome. However, the prematurity rate in
      this cohort remains very high. To date, strategies proposed to decrease the
      prematurity rate have shown inconclusive, if not unfavourable results. METHODS:
      This is a randomised controlled trial to investigate whether a prophylactic
      cervical pessary will lower the incidence of preterm delivery in cases of twin
      twin transfusion syndrome requiring fetoscopic LASER coagulation. Women eligible
      for the study will be randomised after surgery and allocated to either pessary or
      expectant management. The pessary will be left in place until 37 completed weeks
      or earlier if delivery occurs. The primary outcome is delivery before 32
      completed weeks. Secondary outcomes are a composite of adverse neonatal outcome,
      fetal and neonatal death, maternal complications, preterm rupture of membranes
      and hospitalisation for threatened preterm labour. 352 women will be included in
      order to decrease the rate of preterm delivery before 32 weeks' gestation from
      40% to 26% with an alpha-error of 0.05 and 80% power. DISCUSSION: The trial aims
      at clarifying whether the cervical pessary prolongs the pregnancy in cases of
      twin-twin transfusion syndrome regardless of cervical length at the time of
      fetoscopy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01334489 .
      Registered 04 December 2011.

PMID- 28764675
TI  - The role of cognitive stimulation at home in low-income preschoolers' nutrition,
      physical activity and body mass index.
AB  - BACKGROUND: Early childhood obesity disproportionately affects children of low
      socioeconomic status. Children attending Head Start are reported to have an
      obesity rate of 17.9%.This longitudinal study aimed to understand the
      relationship between cognitive stimulation at home and intake of junk food,
      physical activity and body size, for a nationally representative sample of 3- and
      4-year old children entering Head Start. METHODS: We used The Family and Child
      Experiences Survey 2006. Cognitive stimulation at home was measured for 1905
      children at preschool entry using items from the Home Observation Measurement of
      the Environment Short Form. Junk food consumption and physical activity were
      obtained from parent interviews at kindergarten entry. BMI z scores were based on
      CDC national standards. We analyzed the association between early cognitive
      stimulation and junk food consumption, physical activity and BMI, using
      multinomial and binary logistic regression on a weighted sample. RESULTS:
      Children who received moderate levels of cognitive stimulation at home had a 1.5
      increase in the likelihood of consuming low amounts of junk food compared to
      children from low cognitive stimulation environments. Children who received
      moderate and high levels of cognitive stimulation were two and three times,
      respectively, more likely to be physically active than those in low cognitive
      stimulation homes. No direct relationship was identified between cognitive
      stimulation and BMI. CONCLUSION: Prevention and treatment efforts to address
      early childhood obesity may consider strategies that support parents in providing
      cognitively stimulating home environments. Existing evidence-based programs can
      guide intervention in pediatric primary care.

PMID- 28764676
TI  - Outcome and toxicity of radical radiotherapy or concurrent Chemoradiotherapy for
      elderly cervical cancer women.
AB  - BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for
      local advanced cervical cancer. However, for elderly patients, studies are
      limited and the outcomes are controversial. We retrospectively analyzed the
      efficacy and tolerance of radical radiotherapy (RT) or CCRT in elderly cervical
      cancer patients and performed comparisons between them. METHODS: We
      retrospectively analyzed the elderly cervical cancer patients (>=70 years old)
      treated with radical RT or CCRT between January 2006 and December 2014. For
      external beam radiotherapy, 50Gy in 25 fractions or 50.4Gy in 28 fractions were
      delivered via 3-dimensional conformal radiation therapy or intensity modulated
      radiation therapy. High-dose-rate intracavitary brachytherapy was performed with
      a dose of 30-36Gy in 5-7 fractions to point A. Concurrent chemotherapy regimens
      included weekly cisplatin and paclitaxel. RESULTS: Seventy-three patients were
      eligible for this study. Twenty-one(28.8%) and 52(71.2%) patients suffered with
      FIGO stage IB-IIA and IIB-IVA disease, respectively. Twenty-four (32.9%) patients
      received CCRT. The median duration of follow-up was 32.4 months (4.8-118.8
      months). The 3-year overall survival (OS), cancer-specific survival (CSS) and
      disease-free survival (DFS) were 64.9%, 67.8% and 66.5%, respectively. By
      multivariate analysis, CCRT was a significant predictive factor of OS(p = 0.023,
      95% confidence interval [CI]: 1.172-8.860), CSS(p = 0.031, 95% CI: 1.131
      13.908)and DFS(p = 0.045, 95% CI: 1.023 ~ 6.430). The 3-year OS of patients
      received RT and CCRT were 54.3% and 83.1%, CSS were 56.8% and 87.1%, DFS were
      57.6% and 83.3%. There was no treatment related death. Grade 3-4 acute
      hematological, gastrointestinal and urinary toxicity incidences were 31.5%, 19.1%
      and 12.3%, respectively. For grade 3-4 chronic gastrointestinal and genitourinary
      toxicities, the incidences were 4.1% and 2.7%, respectively. Compared with RT,
      CCRT was related with high grade 3-4 hematological toxicity (16.3% and 62.5%
      respectively, p < 0.001), respectively. However, acute nonhematological toxicity
      and chronic toxicity were not significantly different. CONCLUSION: Elderly
      cervical cancer patients could tolerate radical RT and CCRT very well and get a
      favored survival. Compared with RT, CCRT could improve the survival of elder
      cervical cancer patients with similar nonhematological toxicity. CCRT should be
      considered in elderly cervical cancer patients.

PMID- 28764677
TI  - Yarning about fall prevention: community consultation to discuss falls and
      appropriate approaches to fall prevention with older Aboriginal and Torres Strait
      Islander people.
AB  - BACKGROUND: Fall related injury is an emerging issue for older Indigenous people
      worldwide, yet few targeted fall prevention programs are currently available for
      Indigenous populations. In order to inform the development of a new Aboriginal
      specific fall prevention program in Australia, we conducted community
      consultation with older Aboriginal people to identify perceptions and beliefs
      about falls, and to identify desired program elements. METHODS: Yarning Circles
      were held with Aboriginal and Torres Strait Islander people aged 45 years and
      over. Each Yarning Circle was facilitated by an Aboriginal researcher who
      incorporated six indicative questions into each discussion. Questions explored
      the impact of falls on Yarning Circle participants, their current use of fall
      prevention services and investigated Yarning Circle participant's preferences
      regarding the design and mode of delivery of a fall prevention program. RESULTS:
      A total of 76 older Aboriginal people participated in ten Yarning Circles across
      six sites in the state of New South Wales. Participants associated falls with
      physical disability, a loss of emotional well-being and loss of connection to
      family and community. Many participants did not use existing fall prevention
      services due to a lack of availability in their area, having no referral provided
      by their GP and/or being unaware of fall prevention programs in general. Program
      elements identified as important by participants were that it be Aboriginal
      specific, group-based, and on-going, with the flexibility to be tailored to
      specific communities, with free transport provided to and from the program.
      CONCLUSIONS: Older Aboriginal people reported falls to be a priority health
      issue, with a significant impact on their health and well-being. Few older
      Aboriginal people accessed prevention programs, suggesting there is an important
      need for targeted Aboriginal-specific programs. A number of important program
      elements were identified which if incorporated into prevention programs, may help
      to address the rising burden of falls.

PMID- 28764678
TI  - The specific and combined role of domestic violence and mental health disorders
      during pregnancy on new-born health.
AB  - BACKGROUND: Addressing impaired foetal growth is recognized as a public health
      priority. Certain risk factors for this condition, such as poor nutritional
      status at birth, have been found to be highly correlated with poverty. However,
      the role of psychosocial factors, specifically the mother's mental health and
      exposure to violence during pregnancy, have yet to be further explored. Our
      objective was to determine if there is a measurable association between combined
      psychosocial factors, specifically domestic violence and mental disorders, and
      birth outcomes, specifically birth nutritional status and preterm delivery.
      METHODS: We followed 775 women from an underserved, urban area, beginning their
      28th week of gestation. Diagnostic interviews were performed to determine if any
      of the mothers had any of the following disorders: mood disorder, anxiety,
      obsessive-compulsive disorder (OCD), substance dependence, psychotic disorder, or
      anti-social personality disorder. Physical, psychological, and sexual domestic
      violence were also assessed. RESULTS: Domestic violence and mental disorders were
      highly correlated in our sample. About 27.15% of the women in our study
      experienced domestic violence, and about 38.24% of them were diagnosed with
      mental disorders. The main association we found between combined psychosocial
      factors and neonate outcomes was between anxiety (IRR = 1.83; 95%CI = 1.06
      3.17)/physical violence (IRR = 1.95; 95%CI = 1.11-3.42) and the rate of small-for
      gestational age (SGA) in new-borns. More specifically, the combination of anxiety
      (beta = -0.48; 95%CI = -0.85/-0.10) and sexual violence (beta = -1.58; 95%CI = 
      2.61/-0.54) was also associated with birth length. Maternal risk behaviours such
      as smoking, drinking, inadequate prenatal care, and inadequate weight gain could
      not sufficiently explain these associations, suggesting that these psychosocial
      factors may be influencing underlying biological mechanisms. CONCLUSION: Domestic
      violence against women and mental disorders amongst pregnant women are extremely
      prevalent in under-resourced, urban areas and ultimately, have detrimental
      effects on birth outcomes. It is imperative that actions be taken to prevent
      violence and improve mental health during pregnancy.

PMID- 28764679
TI  - Economic evaluation of stepped-care versus usual care for depression and anxiety
      in older adults with vision impairment: randomized controlled trial.
AB  - BACKGROUND: A stepped-care program was found effective in preventing depressive
      and anxiety disorders in older adults with vision impairment. However, before a
      decision can be made about implementation, the cost-effectiveness of this program
      should be investigated. Therefore, we aimed to compare the cost-effectiveness of
      stepped-care versus usual care within low vision rehabilitation. METHODS: An
      economic evaluation from a societal perspective was performed alongside a
      multicenter randomized controlled trial. Data were collected by masked assessors
      during 24 months. Included were 265 older adults with vision impairment and
      subthreshold depression and/or anxiety. They were randomly assigned to stepped
      care plus usual care (n = 131) or usual care alone (n = 134). Stepped-care
      comprised 1) watchful waiting, 2) guided self-help based on cognitive behavioral
      therapy, 3) problem solving treatment, and 4) referral to a general practitioner.
      Costs were based on direct healthcare costs and indirect non-healthcare costs.
      Main outcome measures were quality-adjusted life years (QALYs) and the cumulative
      incidence of major depressive, dysthymic and/or anxiety disorders. Secondary
      outcomes were symptoms of depression and anxiety. RESULTS: Based on intention-to
      treat, significant differences were found in the incidence of depressive/anxiety
      disorders (mean difference 0.17; 95% CI 0.06 to 0.29) and symptoms of anxiety
      (mean difference 1.43, 95% CI 0.10 to 2.77) in favor of stepped-care versus usual
      care; no significant difference was found for QALYs and symptoms of depression.
      Societal costs were non-significantly lower in the stepped-care group compared
      with the usual care group (mean difference: -?877; 95% confidence interval (CI): 
      8039 to 5489). Cost-effectiveness acceptability curves showed that the
      probability of cost-effectiveness was 95% or more at a willingness-to-pay of
      ?33,000 per disorder prevented. The probability that stepped-care was cost
      effective compared to usual care was 59% or more for a ceiling ratio of 0 ?/QALY
      and increased to 65% at 20000 ?/QALY. CONCLUSIONS: This economic evaluation shows
      that stepped-care is dominant to usual care, with a probability of around 60%,
      due to its clinical superiority and its modest cost savings. However, it depends
      on the willingness-to-pay of decision makers whether or not stepped-care is
      considered cost-effective compared with usual care. TRIAL REGISTRATION:
      identifier: NTR3296 , date: 13-02-2012.

PMID- 28764680
TI  - Validation and psychometric properties of the Somatic and Psychological HEalth
      REport (SPHERE) in a young Australian-based population sample using non
      parametric item response theory.
AB  - BACKGROUND: The Somatic and Psychological HEalth REport (SPHERE) is a 34-item
      self-report questionnaire that assesses symptoms of mental distress and
      persistent fatigue. As it was developed as a screening instrument for use mainly
      in primary care-based clinical settings, its validity and psychometric properties
      have not been studied extensively in population-based samples. METHODS: We used
      non-parametric Item Response Theory to assess scale validity and item properties
      of the SPHERE-34 scales, collected through four waves of the Brisbane
      Longitudinal Twin Study (N = 1707, mean age = 12, 51% females; N = 1273, mean age
      = 14, 50% females; N = 1513, mean age = 16, 54% females, N = 1263, mean age = 18,
      56% females). We estimated the heritability of the new scores, their genetic
      correlation, and their predictive ability in a sub-sample (N = 1993) who
      completed the Composite International Diagnostic Interview. RESULTS: After
      excluding items most responsible for noise, sex or wave bias, the SPHERE-34
      questionnaire was reduced to 21 items (SPHERE-21), comprising a 14-item scale for
      anxiety-depression and a 10-item scale for chronic fatigue (3 items overlapping).
      These new scores showed high internal consistency (alpha > 0.78), moderate three
      months reliability (ICC = 0.47-0.58) and item scalability (Hi > 0.23), and were
      positively correlated (phenotypic correlations r = 0.57-0.70; rG = 0.77-1.00).
      Heritability estimates ranged from 0.27 to 0.51. In addition, both scores were
      associated with later DSM-IV diagnoses of MDD, social anxiety and alcohol
      dependence (OR in 1.23-1.47). Finally, a post-hoc comparison showed that several
      psychometric properties of the SPHERE-21 were similar to those of the Beck
      Depression Inventory. CONCLUSIONS: The scales of SPHERE-21 measure valid and
      comparable constructs across sex and age groups (from 9 to 28 years). SPHERE-21
      scores are heritable, genetically correlated and show good predictive ability of
      mental health in an Australian-based population sample of young people.

PMID- 28764681
TI  - A brief, trauma-informed intervention increases safety behavior and reduces HIV
      risk for drug-involved women who trade sex.
AB  - BACKGROUND: Female sex workers (FSWs) are an important population for HIV
      acquisition and transmission. Their risks are shaped by behavioral, sexual
      network, and structural level factors. Violence is pervasive and associated with
      HIV risk behavior and infection, yet interventions to address the dual epidemics
      of violence and HIV among FSWs are limited. METHODS: We used participatory
      methods to develop a brief, trauma-informed intervention, INSPIRE (Integrating
      Safety Promotion with HIV Risk Reduction), to improve safety and reduce HIV risk
      for FSWs. A quasi-experimental, single group pretest-posttest study evaluated
      intervention feasibility, acceptability and efficacy among FSWs in Baltimore, MD,
      most of whom were drug-involved (baseline n = 60; follow-up n = 39 [65%]; non
      differential by demographics or outcomes). Qualitative data collected at follow
      up contextualizes findings. RESULTS: Based on community partnership and FSW
      input, emergent goals included violence-related support, connection with
      services, and buffering against structural forces that blame FSWs for violence.
      Qualitative and quantitative results demonstrate feasibility and acceptability.
      At follow-up, improvements were seen in avoidance of client condom negotiation (p
      = 0.04), and frequency of sex trade under the influence of drugs or alcohol (p =
      0.04). Women's safety behavior increased (p < 0.001). Participants improved
      knowledge and use of sexual violence support (p < 0.01) and use of intimate
      partner violence support (p < 0.01). By follow-up, most respondents (68.4%) knew
      at least one program to obtain assistance reporting violence to police. Over the
      short follow-up period, client violence increased. In reflecting on intervention
      acceptability, participants emphasized the value of a safe and supportive space
      to discuss violence. DISCUSSION: This brief, trauma-informed intervention was
      feasible and highly acceptable to FSWs. It prompted safety behavior, mitigated
      sex trade under the influence, and bolstered confidence in condom negotiation.
      INSPIRE influenced endpoints deemed valuable by community partners, specifically
      improving connection to support services and building confidence in the face of
      myths that falsely blame sex workers for violence. Violence persisted; prevention
      also requires targeting perpetrators, and longer follow-up durations as women
      acquire safety skills. This pilot study informs scalable interventions that
      address trauma and its impact on HIV acquisition and care trajectories for FSWs.
      CONCLUSION: Addressing violence in the context of HIV prevention is feasible,
      acceptable to FSWs, and can improve safety and reduce HIV risk, thus supporting
      FSW health and human rights.

PMID- 28764682
TI  - Informing tobacco control policy in Jordan: assessing the effectiveness of
      pictorial warning labels on cigarette packs.
AB  - BACKGROUND: Pictorial warning labels (PWLs) deter initiation and motivate
      quitting. Assessing PWLs is important to track effectiveness and wear out. Jordan
      introduced an updated set of PWLs in 2013. This study assessed the effectiveness
      of the set after 2.5 years on the market. METHODS: We administered a survey in a
      cross-sectional sample of young adults aged 17-26 years. For convenience,
      respondents were recruited on university campuses. For heterogeneity, respondents
      were solicited from the different schools in four geographically diverse
      university campuses. The study compared perceptions of effectiveness surveyed in
      2015 to perceptions gauged in 2010 during a pre-launch evaluation exercise.
      Outcomes of interest were: salience, fear evocation, adding information, and
      ability to motivate quitting smoking (for smokers) or deterring starting (for non
      smokers). RESULTS: Results indicate awareness of the set among smokers and non
      smokers, and their recall of at least one PWL message. Results also indicate
      effectiveness of the set: (1) 1/3 smokers who frequently saw them reported PWLs
      to trigger considering quitting, (2) and among both smokers and non-smokers the
      set in 2015 sustained ability to motivate quitting and staying smoke-free.
      However, results uncover erosion of salience, suggesting that the set has reached
      its end of life. Finally, results reveal variability in performance among PWLs;
      the one PWL that depicts human suffering significantly outperformed the others,
      and its ability to motivate was most strongly associated with its ability to
      evoke fear. CONCLUSION: Based on the early signs of wear-out (i.e. erosion of
      salience), and understanding the importance of sustaining upstream outcomes
      (especially fear evocation) to sustain motivation, we recommend retiring this set
      of PWLs and replacing it with a stronger set in line with proven standards.

PMID- 28764683
TI  - Association of calcium sensing receptor polymorphisms at rs1801725 with
      circulating calcium in breast cancer patients.
AB  - BACKGROUND: Breast cancer (BC) patients with late-stage and/or rapidly growing
      tumors are prone to develop high serum calcium levels which have been shown to be
      associated with larger and aggressive breast tumors in post and premenopausal
      women respectively. Given the pivotal role of the calcium sensing receptor (CaSR)
      in calcium homeostasis, we evaluated whether polymorphisms of the CASR gene at
      rs1801725 and rs1801726 SNPs in exon 7, are associated with circulating calcium
      levels in African American and Caucasian control subjects and BC cases. METHODS:
      In this retrospective case-control study, we assessed the mean circulating
      calcium levels, the distribution of two inactivating CaSR SNPs at rs1801725 and
      rs1801726 in 199 cases and 384 age-matched controls, and used multivariable
      regression analysis to determine whether these SNPs are associated with
      circulating calcium in control subjects and BC cases. RESULTS: We found that the
      mean circulating calcium levels in African American subjects were higher than
      those in Caucasian subjects (p < 0.001). As expected, the mean calcium levels
      were higher in BC cases compared to control subjects (p < 0.001), but the calcium
      levels in BC patients were independent of race. We also show that in BC cases and
      control subjects, the major alleles at rs1801725 (G/T, A986S) and at rs1801726
      (C/G, Q1011E) were common among Caucasians and African Americans respectively.
      Compared to the wild type alleles, polymorphisms at the rs1801725 SNP were
      associated with higher calcium levels (p = 0.006) while those at rs1801726 were
      not. Using multivariable linear mixed-effects models and adjusting for age and
      race, we show that circulating calcium levels in BC cases were associated with
      tumor grade (p = 0.009), clinical stage (p = 0.003) and more importantly, with
      inactivating mutations of the CASR at the rs1801725 SNP (p = 0.038). CONCLUSIONS:
      These data suggest that decreased sensitivity of the CaSR to calcium due to
      inactivating polymorphisms at rs1801725, may predispose up to 20% of BC cases to
      high circulating calcium-associated larger and/or aggressive breast tumors.

PMID- 28764684
TI  - Intraoperative optical coherence tomography assisted analysis of pars Plana
      vitrectomy for retinal detachment in morning glory syndrome: a case report.
AB  - BACKGROUND: The pathogenesis of non-rhegmatogenous retinal detachment (non-RRD)
      associated with morning glory syndrome (MGS) is not established, as well as best
      surgical approach to treat RD. Our purpose was to analyse intraoperative optical
      coherence tomography data (iOCT) in all steps of pars plana vitrectomy (PPV) for
      non-RRD in MGS, in order to follow pathophysiological aspects of the disease and
      to understand the tissues behaviour during surgical workflow. CASE PRESENTATION:
      Intraoperative spectral domain optical coherent tomography (iSD-OCT) assisted PPV
      using Rescan 700 (Carl Zeiss Meditech, Jena, Germany) with epiretinal membrane
      (ERM) and internal retinal membrane (ILM) peeling, and air endotamponade was
      performed on the only eye of a 21 years old female with non-RRD associated with
      MGS. BCVA, pre-, intra- and postoperative OCT were performed along with standard
      ocular examination. iOCT video and snapshots were analysed intra- and
      postoperatively using post-processing approach using graphic software. The
      progression of non-RRD resulted in best corrected visual acuity (BCVA) decrease
      from 0.8 to 0.2. Triamcinolone enhanced iOCT imaging revealed strong vitreous
      traction and adhesion above the macula and optic disc. Internal limiting membrane
      was peeled under iOCT control to prevent the peeling of inner layers of the
      retinal schisis. No retinal break was detected, and only air endotamponade was
      performed. The retina reattached during first 4 weeks of follow-up with gradual
      resolution of intraretinal- and subretinal fluid, and remained stable in 12
      months. BCVA improved to 0.8. CONCLUSION: Based on iSD-OCT findings we assume
      that non-RRD in this case of MGS is caused primarily by the vitreous traction
      with further possible formation of the retinal breaks. Retinal reattachment
      reached only with air endotamponade strongly advocates the tractional component
      of non-RRD and retinal schisis assotiated with MGS. Early PPV for central non-RRD
      and retinal schisis with the use of iOCT can be performed in more safe and
      controlled manner and has to be considered to reduce the risk of retinal break
      formation and to prevent the central vision loss.

PMID- 28764685
TI  - Notch1 signaling induces epithelial-mesenchymal transition in lens epithelium
      cells during hypoxia.
AB  - BACKGROUND: Posterior Capsular Opacification (PCO) is one of the most common
      complications of cataract surgery which can result in severe visual damage.
      Epithelial-Mesenchymal Transition (EMT) of lens epithelium cells (LEC) is the
      pathological basis of PCO. Recent research showed that hypoxia acted as an
      inducer of EMT through a Notch1/Snail1/E-cadherin pathway. However, it remains
      unclear whether the Notch1/Snail1/E-cadherin pathway is involved in PCO under
      hypoxia. METHODS: The morphology of SRA01/04 cells treating with Cobalt Chloride
      (CoCl2) was observed and the markers of EMT and Notch1/Snail1/E-cadherin pathway
      were analyzed by Western blot and Immunocytochemistry assay. Transwell invasion
      assay and Wound healing assay were used to detected the effect of p3 * FLAG-CMV-7
      NICD1 transfection on the SRA01/04 cells. RESULTS: The SRA01/04 cells lost cell
      polarity and cell junction culturing with CoCl2. The expression of Keratin,
      Hypoxia-inducible factor-1 alpha (HIF-1alpha), Notch1, Snail1were upregulated, on
      the other side, Fibronectin and E-cadherin were downregulated in hypoxia.
      Furthermore, the overexpression of Notch1 induced the expression of E-cadherin
      and increased the invasion and migration ability of SRA01/04 cells. CONCLUSIONS:
      These results suggest that Notch1/Snail1/E-cadherin pathway facilitates the EMT
      through HIF-1alpha in SRA01/04 cells during hypoxia and promotes LEC motility.

PMID- 28764686
TI  - Household preferences for reducing greenhouse gas emissions in four European high
      income countries: Does health information matter? A mixed-methods study protocol.
AB  - BACKGROUND: It is now universally acknowledged that climate change constitutes a
      major threat to human health. At the same time, some of the measures to reduce
      greenhouse gas emissions, so-called climate change mitigation measures, have
      significant health co-benefits (e.g., walking or cycling more; eating less meat).
      The goal of limiting global warming to 1,5 degrees  Celsius set by the Conference
      of the Parties to the United Nations Framework Convention on Climate Change in
      Paris in 2015 can only be reached if all stakeholders, including households, take
      actions to mitigate climate change. Results on whether framing mitigation
      measures in terms of their health co-benefits increases the likelihood of their
      implementation are inconsistent. The present study protocol describes the
      transdisciplinary project HOPE (HOuseholds' Preferences for reducing greenhouse
      gas emissions in four European high-income countries) that investigates the role
      of health co-benefits in households' decision making on climate change mitigation
      measures in urban households in France, Germany, Norway and Sweden. METHODS: HOPE
      employs a mixed-methods approach combining status-quo carbon footprint
      assessments, simulations of the reduction of households' carbon footprints, and
      qualitative in-depth interviews with a subgroup of households. Furthermore, a
      policy analysis of current household oriented climate policies is conducted. In
      the simulation of the reduction of households' carbon footprints, half of the
      households are provided with information on health co-benefits of climate change
      mitigation measures, the other half is not. Households' willingness to implement
      the measures is assessed and compared in between-group analyses of variance.
      DISCUSSION: This is one of the first comprehensive mixed-methods approaches to
      investigate which mitigation measures households are most willing to implement in
      order to reach the 1,5 degrees  target set by the Paris Agreement, and whether
      health co-benefits can serve as a motivator for households to implement these
      measures. The comparison of the empirical data with current climate policies will
      provide knowledge for tailoring effective climate change mitigation and health
      policies.

PMID- 28764687
TI  - Sustainability and scalability of a volunteer-based primary care intervention
      (Health TAPESTRY): a mixed-methods analysis.
AB  - BACKGROUND: Chronic diseases are a significant public health concern,
      particularly in older adults. To address the delivery of health care services to
      optimally meet the needs of older adults with multiple chronic diseases, Health
      TAPESTRY (Teams Advancing Patient Experience: Strengthening Quality) uses a novel
      approach that involves patient home visits by trained volunteers to collect and
      transmit relevant health information using e-health technology to inform
      appropriate care from an inter-professional healthcare team. Health TAPESTRY was
      implemented, pilot tested, and evaluated in a randomized controlled trial
      (analysis underway). Knowledge translation (KT) interventions such as Health
      TAPESTRY should involve an investigation of their sustainability and scalability
      determinants to inform further implementation. However, this is seldom considered
      in research or considered early enough, so the objectives of this study were to
      assess the sustainability and scalability potential of Health TAPESTRY from the
      perspective of the team who developed and pilot-tested it. METHODS: Our
      objectives were addressed using a sequential mixed-methods approach involving the
      administration of a validated, sustainability survey developed by the National
      Health Service (NHS) to all members of the Health TAPESTRY team who were actively
      involved in the development, implementation and pilot evaluation of the
      intervention (Phase 1: n = 38). Mean sustainability scores were calculated to
      identify the best potential for improvement across sustainability factors. Phase
      2 was a qualitative study of interviews with purposively selected Health TAPESTRY
      team members to gain a more in-depth understanding of the factors that influence
      the sustainability and scalability Health TAPESTRY. Two independent reviewers
      coded transcribed interviews and completed a multi-step thematic analysis.
      Outcomes were participant perceptions of the determinants influencing the
      sustainability and scalability of Health TAPESTRY. RESULTS: Twenty Health
      TAPESTRY team members (53% response rate) completed the NHS sustainability
      survey. The overall mean sustainability score was 64.6 (range 22.8-96.8).
      Important opportunities for improving sustainability were better staff
      involvement and training, clinical leadership engagement, and infrastructure for
      sustainability. Interviews with 25 participants (response rate 60%) showed that
      factors influencing the sustainability and scalability of Health TAPESTRY emerged
      across two dimensions: I) Health TAPESTRY operations (development and
      implementation activities undertaken by the central team); and II) the Health
      TAPESTRY intervention (factors specific to the intervention and its elements).
      Resource capacity appears to be an important factor to consider for Health
      TAPESTRY operations as it was identified across both sustainability and
      scalability factors; and perceived lack of interprofessional team and volunteer
      resource capacity and the need for stakeholder buy-in are important
      considerations for the Health TAPESTRY intervention. We used these findings to
      create actionable recommendations to initiate dialogue among Health TAPESTRY team
      members to improve the intervention. CONCLUSIONS: Our study identified
      sustainability and scalability determinants of the Health TAPESTRY intervention
      that can be used to optimize its potential for impact. Next steps will involve
      using findings to inform a guide to facilitate sustainability and scalability of
      Health TAPESTRY in other jurisdictions considering its adoption. Our findings
      build on the limited current knowledge of sustainability, and advances KT science
      related to the sustainability and scalability of KT interventions.

PMID- 28764688
TI  - Developing a patient decision aid for the treatment of women with early stage
      breast cancer: the struggle between simplicity and complexity.
AB  - BACKGROUND: A patient decision aid (PtDA) can support shared decision making
      (SDM) in preference-sensitive care, with more than one clinically applicable
      treatment option. The development of a PtDA is a complex process, involving
      several steps, such as designing, developing and testing the draft with all the
      stakeholders, known as alpha testing. This is followed by testing in 'real life'
      situations, known as beta testing, and then finalising the definite version. Our
      aim was developing and alpha testing a PtDA for primary treatment of early stage
      breast cancer, ensuring that the tool is considered relevant, valid and feasible
      by patients and professionals. METHODS: Our qualitative descriptive study applied
      various methods including face-to-face think-aloud interviews, a focus group and
      semi-structured telephone interviews. The study population consisted of breast
      cancer patients facing the choice between breast-conserving therapy with or
      without preceding neo-adjuvant chemotherapy and mastectomy, and professionals
      involved in breast cancer care in dedicated multidisciplinary breast cancer
      teams. RESULTS: A PtDA was developed in four iterative test rounds, taking nearly
      2 years, involving 26 patients and 26 professionals. While the research group
      initially opted for simplicity for the sake of implementation, the clinicians
      objected that the complexity of the decision could not be ignored. Other topics
      of concern were the conflicting views of professionals and patients regarding
      side effects, the amount of information and how to present it. CONCLUSION: The
      development was an extensive process, because the professionals rejected the
      simplifications proposed by the research group. This resulted in the development
      of a completely new draft PtDA, which took double the expected time and
      resources. The final version of the PtDA appeared to be well-appreciated by
      professionals and patients, although its acceptability will only be proven in
      actual practice (beta testing). TRIAL REGISTRATION: NTR TC 5721 .

PMID- 28764689
TI  - Heterogeneity in high-risk prostate cancer treated with high-dose radiation
      therapy and androgen deprivation therapy.
AB  - BACKGROUND: Our aim was to assess the heterogeneity of high-risk (HR) prostate
      cancer managed with high-dose external beam radiotherapy (EBRT) with androgen
      deprivation therapy (ADT). METHODS: We identified 547 patients who were treated
      with modern EBRT from 1997 to 2013, of whom 98% received ADT. We analyzed
      biochemical relapse-free survival (bRFS) and distant metastases-free survival
      (DMFS). RESULTS: Median EBRT dose was 74 Gy, and median ADT duration was 8
      months. At 5 years, the DMFS was 85%. On multivariate analysis, significant
      predictors of shorter bRFS were biopsy Gleason score (bGS) of 8 to 10, higher
      prostate-specific antigen (PSA) level, shorter duration of ADT and lower
      radiation dose while predictors of shorter DMFS were bGS of 8 to 10, higher PSA
      level, and lower radiation dose. We identified an unfavorable high-risk (UHR)
      group of with 2-3 HR factors based on 2015 National Comprehensive Cancer Network
      (NCCN) criteria and a favorable high-risk (FHR) group, with 1 HR feature.
      Comparing very-HR prostate cancer, UHR & FHR, 5 year bRFS rates were 58.2%,
      66.2%, and 69.2%, and 5 year DMFS rates were 78.4%, 81.2%, and 88.0%. CONCLUSION:
      Patients with multiple HR factors have worse outcome than patients with 1 HR
      factor. Future studies should account for this heterogeneity in HR prostate
      cancer.

PMID- 28764690
TI  - Delayed anti-TNF therapy increases the risk of total knee replacement in patients
      with severe rheumatoid arthritis.
AB  - BACKGROUND: This study evaluated the effect of early anti-tumor necrosis factor
      (TNF) therapy in patients with severe rheumatoid arthritis (RA) on the subsequent
      risk of total knee replacement (TKR) surgery. METHODS: This retrospective
      observational study included a hospital-based cohort of 200 patients diagnosed
      with severe RA who received treatment with anti-TNF therapy between 2003 and
      2014. Clinical parameters including age, sex, body mass index, and the time from
      the diagnosis of RA to the initiation of anti-TNF therapy were analyzed. RESULTS:
      Of the 200 enrolled patients, 84 underwent an early intervention (<=3 years from
      the diagnosis of RA to the initiation of anti-TNF therapy), and 116 underwent a
      late intervention(>3 years from the diagnosis of RA to the initiation of anti-TNF
      therapy). Five (6.0%) patients in the early intervention group underwent TKR
      compared to 31 (26.7%) in the late intervention group (p = 0.023). After
      adjusting for confounding factors, the late intervention group still had a
      significantly higher risk of TKR (p = 0.004; odds ratio, 5.572; 95% confidence
      interval, 1.933-16.062). Those receiving treatment including methotrexate had a
      lower risk of TKR (p = 0.004; odds ratio, 0.287; 95% confidence interval, 0.122
      0.672). CONCLUSIONS: Delayed initiation of anti-TNF therapy in the treatment of
      severe RA was associated with an increased risk of TKR surgery. Adding
      methotrexate treatment decreased the risk of future TKR.

PMID- 28764691
TI  - Kneeling and standing up from a chair as performance-based tests to evaluate knee
      function in the high-flexion range: a randomized controlled trial comparing a
      conventional and a high-flexion TKA design.
AB  - BACKGROUND: We compared the functional outcome between conventional and high
      flexion total knee arthroplasty (TKA) using kneeling and sit-to-stand tests at 1
      year post-operative. In addition, the patient's daily functioning, pain and
      satisfaction were quantified using questionnaires. METHODS: We randomly assigned
      56 patients to receive either a conventional or a high-flexion TKA. Primary
      outcomes were maximum flexion angle and maximum thigh-calf contact measured
      during kneeling at 1 year post operatively. Secondary outcomes were the angular
      knee velocity and ground reaction force ratio measured during sit-to-stand
      performance tests, and questionnaires. RESULTS: At one year post-operative,
      maximum knee flexion during kneeling was higher for the high-flexion TKA group
      (median 128.02 degrees  (range 108-146)) compared to the conventional TKA group
      (119.13 degrees  (range 72-135)) (p = 0.03). Maximum thigh-calf contact force was
      higher for the high flexion TKA group (median 17.82 N (range 2.98-114.64))
      compared to the conventional TKA group (median 9.37 N (range 0.33-46.58))(p =
      0.04). The sit-to-stand tests showed a significantly higher angular knee velocity
      in the conventional TKA group (12.12 rad/s (95%CI 0.34-23.91); p = 0.04). There
      were no significant differences between groups in ground reaction force ratios
      and patient-reported outcome scores. CONCLUSION: Although no differences were
      found in patient-reported outcome scores, differences in performance-based tests
      were clearly apparent. Standing up from a chair at 90 degrees  of knee flexion
      appeared to be easier for the conventional group. The kneeling test revealed
      significantly higher weight-bearing knee flexion for the high-flex group. Hence,
      if kneeling is an important activity for a patient a high-flex design may be
      recommendable. TRIAL REGISTRATION: The study was retrospectively registered in
      ClinicalTrials.gov under identifier NCT00899041 (date of registration: May 11,
      2009).

PMID- 28764693
TI  - The relationship between demographic- and disease-related variables and health
      related quality of life in patients with axial spondyloarthritis.
AB  - BACKGROUND: Axial spondyloarthritis (ax-SpA) is a chronic inflammatory disease of
      the spine causing pain, stiffness, loss in physical function, and fatigue.
      Therefore, the physical and psychological burden of having this chronic disease
      can reduce the quality of life. We aimed to explore the relationship between
      demographic- and disease-related variables and health-related quality of life
      (HRQoL) in patients with ax-SpA. METHODS: Demographic- and disease-related, HRQoL
      related and treatment data were collected. Disease measures included the Bath
      Ankylosing Spondylitis Disease Activity Index (BASDAI), the BAS Functional Index
      (BASFI), the BAS Global (BAS-G) score, the Maastricht Ankylosing Spondylitis
      Enthesitis Score (MASES), the Health Assessment Questionnaire (HAQ) and co
      morbidity. HRQoL was assessed using the SF-36 and the utility measures SF-6D and
      15D. Variables associated with HRQoL were identified in unadjusted and adjusted
      analyses. RESULTS: We examined 380 patients with ax-SpA (67% men) with a mean age
      of 46 years. Among them, 86% reported exercising >1 h per week. Mean values were
      as follows: BASDAI, 3.17; MASES, 3.19; BASFI, 2.71; BAS-G. 3.88; and HAQ, 0.56.
      The percentage of current users of NSAIDs was 44%, and of DMARDs 23%. In
      multivariate analyses, exercising 1-3 h per week (B = 2.73, p = 0.022) and
      exercising >3 h per week (B = 2.71, p = 0.020), lower HAQ scores (B = -4.61, p =
      0.001), lower BASFI scores (B = -1.05, p = 0.010) and lower BAS-G scores (B = 
      0.91, p = 0.001) were independently associated with higher SF-36-PCS scores,
      whereas modest alcohol consumption (B = 4.63, p = 0.018) and a lower BAS-G score
      (B = -1.73, p < 0.001) were independently associated with higher SF-36-MCS
      scores. Exercising 1-3 h per week (B = 0.032, p = 0.004) and exercising >3 h per
      week (B = 0.036, p = 0.001), lower HAQ scores (B = -0.051, p < 0.001), lower BAS
      G scores (B = -0.010, p < 0.001) and co-morbidity (B = -0.014, p = 0.004) were
      independently associated with higher 15D scores. Finally, exercising 1-3 h per
      week (B = 0.045, p = 0.001) and exercising > 3 h per week (B = 0.053, p < 0.001),
      lower HAQ scores (B = -0.054, p = 0.001) and lower BAS-G scores (B = -0.020, p <
      0.001) were associated with higher SF-6D scores. CONCLUSIONS: In patients with ax
      SpA, a low level of physical activity, impaired physical function and impaired
      general well-being were independently and consistently associated with a
      decreased HRQoL across all applied measures.

PMID- 28764692
TI  - African swine fever virus infection in Classical swine fever subclinically
      infected wild boars.
AB  - BACKGROUND: Recently moderate-virulence classical swine fever virus (CSFV)
      strains have been proven capable of generating postnatal persistent infection
      (PI), defined by the maintenance of viremia and the inability to generate CSFV
      specific immune responses in animals. These animals also showed a type I
      interferon blockade in the absence of clinical signs. In this study, we assessed
      the infection generated in 7-week-old CSFV PI wild boars after infection with the
      African swine fever virus (ASFV). The wild boars were divided in two groups and
      were infected with ASFV. Group A comprised boars who were CSFV PI in a
      subclinical form and Group B comprised pestivirus-free wild boars. Some relevant
      parameters related to CSFV replication and the immune response of CSFV PI animals
      were studied. Additionally, serum soluble factors such as IFN-alpha, TNF-alpha,
      IL-6, IL-10, IFN-gamma and sCD163 were analysed before and after ASFV infection
      to assess their role in disease progression. RESULTS: After ASFV infection, only
      the CSFV PI wild boars showed progressive acute haemorrhagic disease; however,
      the survival rates following ASFV infection was similar in both experimental
      groups. Notwithstanding, the CSFV RNA load of CSFV PI animals remained unaltered
      over the study; likewise, the ASFV DNA load detected after infection was similar
      between groups. Interestingly, systemic type I FN-alpha and IL-10 levels in sera
      were almost undetectable in CSFV PI animals, yet detectable in Group B, while
      detectable levels of IFN-gamma were found in both groups. Finally, the flow
      cytometry analysis showed an increase in myelomonocytic cells (CD172a+) and a
      decrease in CD4+ T cells in the PBMCs from CSFV PI animals after ASFV infection.
      CONCLUSIONS: Our results showed that the immune response plays a role in the
      progression of disease in CSFV subclinically infected wild boars after ASFV
      infection, and the immune response comprised the systemic type I interferon
      blockade. ASFV does not produce any interference with CSFV replication, or vice
      versa. ASFV infection could be a trigger factor for the disease progression in
      CSFV PI animals, as their survival after ASFV was similar to that of the
      pestivirus-free ASFV-infected group. This fact suggests a high resistance in CSFV
      PI animals even against a virus like ASFV; this may mean that there are relevant
      implications for CSF control in endemic countries. The diagnosis of ASFV and CSFV
      co-infection in endemic countries cannot be ruled out and need to be studied in
      greater depth.

PMID- 28764694
TI  - Predictors of haematocrit in lumbar fusion for lumbar disc herniation: a surgical
      assessment.
AB  - BACKGROUND: Low haematocrit (Hct) is associated with a higher rate of post
      operative complications, increased mortality, and additional medical costs
      following cardiac surgery. Predictors of post-operative Hct in lumbar fusion are
      unclear and may be beneficial in avoiding adverse surgical outcomes. METHODS: A
      total of 704 lumbar disc herniation patients (385 males, 319 females) who
      underwent primary lumbar fusion surgery were reviewed in this retrospective
      study. RESULTS: In the 687 patients who met the selection criteria, the pre
      operative Hct was 41.23 +/- 4.57%, the post-operative Hct was 32.61 +/- 4.52%,
      the peri-operative Hct decline was 8.62 +/- 4.07%, the estimated intra-operative
      blood loss was 586.76 +/- 346.62 mL, and the post-operative drainage was 489.33
      +/- 274.32 mL. Pre-operative Hct, estimated blood volume, estimated intra
      operative blood loss, post-operative drainage, allogeneic blood transfusion, and
      age showed significant correlations with post-operative Hct, and all factors were
      involved in the final multiple regression model. Patients who received intensive
      care had lower post-operative Hct values, and the length of post-operative
      hospital stay was negatively correlated with post-operative Hct. CONCLUSIONS:
      Dangerously low post-operative Hct is related to the length of ICU stay and post
      operative hospital stay. Age, pre-operative Hct, intra-operative blood loss, post
      operative drainage, and units of allogeneic blood transfusion are significant
      predictors of post-operative Hct and Hct decline. Hct variations during the
      operation make the calculation of total blood loss difficult.

PMID- 28764695
TI  - Compliance with telephone triage advice among adults aged 45 years and older: an
      Australian data linkage study.
AB  - BACKGROUND: Middle-aged and older patients are prominent users of telephone
      triage services for timely access to health information and appropriate
      referrals. Non-compliance with advice to seek appropriate care could potentially
      lead to poorer health outcomes among those patients. It is imperative to assess
      the extent to which middle-aged and older patients follow triage advice and how
      this varies according to their socio-demographic, lifestyle and health
      characteristics as well as features of the call. METHODS: Records of calls to the
      Australian healthdirect helpline (July 2008-December 2011) were linked to
      baseline questionnaire data from the 45 and Up Study (participants age >= 45
      years), records of emergency department (ED) presentations, hospital admissions,
      and medical consultation claims. Outcomes of the call included compliance with
      the advice "Attend ED immediately"; "See a doctor (immediately, within 4 hours,
      or within 24 hours)"; "Self-care"; and self-referral to ED or hospital within 24
      h when given a self-care or low-urgency care advice. Multivariable logistic
      regression was used to investigate associations between call outcomes and patient
      and call characteristics. RESULTS: This study included 8406 adults (age >= 45
      years) who were subjects of 11,088 calls to the healthdirect helpline. Rates of
      compliance with the advices "Attend ED immediately", "See a doctor" and "Self
      care" were 68.6%, 64.6% and 77.5% respectively, while self-referral to ED within
      24 h followed 7.0% of calls. Compliance with the advice "Attend ED immediately"
      was higher among patients who had three or more positive lifestyle behaviours,
      called after-hours, or stated that their original intention was to attend ED,
      while it was lower among those who lived in rural and remote areas or reported
      high or very high levels of psychological distress. Compliance with the advice
      "See a doctor" was higher in patients who were aged >=65 years, worked full-time,
      or lived in socio-economically advantaged areas, when another person made the
      call on the patient's behalf, and when the original intention was to seek care
      from an ED or a doctor. It was lower among patients in rural and remote areas and
      those taking five medications or more. Patients aged >=65 years were less likely
      to comply with the advice "Self-care". The rates of self-referral to ED within 24
      h were greater in patients from disadvantaged areas, among calls made after-hours
      or by another person, and when the original intention was to attend ED. Patients
      who were given a self-care or low-urgency care advice, whose calls concerned
      bleeding, cardiac, gastrointestinal, head and facial injury symptoms, were more
      likely to self-refer to ED. CONCLUSIONS: Compliance with telephone triage advice
      among middle-age and older patients varied substantially according to both
      patient- and call-related factors. Knowledge about the patients who are less
      likely to comply with telephone triage advice, and about characteristics of calls
      that may influence compliance, will assist in refining patient triage protocols
      and referral pathways, training staff and tailoring service design and delivery
      to achieve optimal patient compliance.

PMID- 28764696
TI  - Healthcare Quality Improvement and 'work engagement'; concluding results from a
      national, longitudinal, cross-sectional study of the 'Productive Ward-Releasing
      Time to Care' Programme.
AB  - BACKGROUND: Concerns about patient safety and reducing harm have led to a
      particular focus on initiatives that improve healthcare quality. However Quality
      Improvement (QI) initiatives have in the past typically faltered because they
      fail to fully engage healthcare professionals, resulting in apathy and resistance
      amongst this group of key stakeholders. Productive Ward: Releasing Time to Care
      (PW) is a ward-based QI programme created to help ward-based teams redesign and
      streamline the way that they work; leaving more time to care for patients. PW is
      designed to engage and empower ward-based teams to improve the safety, quality
      and delivery of care. METHODS: The main objective of this study was to explore
      whether PW sustains the 'engagement' of ward-based teams by examining the
      longitudinal effect that the national QI programme had on the 'work-engagement'
      of ward-based teams in Ireland. Utilising the Utrecht Work Engagement Scale
      questionnaire (UWES-17), we surveyed nine PW (intervention) sites from typical
      acute Medical/Surgical, Rehabilitation and Elderly services (representing the
      entire cohort of a national phase of PW implementation in Ireland) and a cohort
      of matched control sites. The numbers surveyed from the PW group at T1 (up to 3
      months after commencing the programme) totalled 253 ward-team members and 249
      from the control group. At T2 (12 months later), the survey was repeated with 233
      ward-team members from the PW sites and 236 from the control group. RESULTS:
      Overall findings demonstrated that those involved in the QI initiative had higher
      'engagement' scores at T1 and T2 in comparison to the control group. Total
      'engagement' score (TES), and its 3 dimensions, were all significantly higher in
      the PW group at T1, but only the Vigour dimension remained significantly higher
      at T2 (p = 0.006). CONCLUSION: Our results lend some support to the assertions of
      the PW initiative itself and suggest that when compared to a control group, ward
      based teams involved in the QI programme are more likely to be 'engaged' by it
      and its associated improvement activities and that this is maintained over time.
      However, only the Vigour dimension of 'engagement' remained significantly higher
      in the PW over time.

PMID- 28764697
TI  - Femur first surgical technique: a smart non-computer-based procedure to achieve
      the combined anteversion in primary total hip arthroplasty.
AB  - BACKGROUND: The relevance of prosthetic component orientation to prevent
      dislocation and impingement following total hip arthroplasty (THA) has been
      widely accepted. We investigated the use of a non-computer-based surgery to
      address the reciprocal orientation of the acetabular and femoral components.
      METHODS: In the femur first technique, the cup is positioned relative to the
      stem. When the definitive antetorsion of femoral component is fixed, the cup is
      positioned in a compliant anteversion to the stem. Clinical and radiographic
      assessments were performed before and 3 months after THA. Radiographic assessment
      was performed in standing position with the EOS 2D/3D radiography system. 3D
      images were used to preoperative anterior pelvic plane (APP) angle, postoperative
      acetabular inclination (AI) and anteversion (AA), and postoperative stem
      antetorsion. Clinical assessment was performed with Harris Hip Score (HHS).
      RESULTS: Forty patients (40 hips) underwent primary THA with an average age of 61
      years (range, 36-84). Average HHS increased from 43 +/- 5 (range, 37-52)
      preoperatively to 97 +/- 6 (range, 86-100) at the last follow-up (P < 0.0001).
      Average combined anteversion value of cup with liner and stem was 38 degrees  +/-
      9 degrees  (range, 12 degrees -55 degrees ). Average AI value of cup with liner
      was 39 degrees  +/- 6 degrees  (range, 30 degrees -55 degrees ) in the group with
      standard stem and 45 degrees  +/- 7 degrees  (range, 39 degrees -58 degrees ) in
      the group with varized stem (P = 0.007). Relationship analysis showed no
      correlation between the combined anteversion values of the cup with liner and
      stem with APP angle values (r = 0.26, P = 0.87). CONCLUSIONS: Femur first
      technique allows the surgeon to achieve a combined anteversion ranging from 25
      degrees  to 50 degrees  with a cup inclination ranging from 30 degrees  to 50
      degrees . The cup is positioned according to the functional plane of the patient
      regardless the preoperative pelvic tilt.

PMID- 28764698
TI  - Erratum to: cluster randomized evaluation of adolescent girls empowerment
      Programme (AGEP): study protocol.

PMID- 28764699
TI  - Development of the organisational health literacy responsiveness (Org-HLR)
      framework in collaboration with health and social services professionals.
AB  - BACKGROUND: The health literacy skills required by individuals to interact
      effectively with health services depends on the complexity of those services, and
      the demands they place on people. Public health and social service organisations
      have a responsibility to provide services and information in ways that promote
      equitable access and engagement, that are responsive to diverse needs and
      preferences, and support people to participate in decisions regarding their
      health and wellbeing. The aim of this study was to develop a conceptual framework
      describing the characteristics of health literacy responsive organisations.
      METHODS: Concept mapping (CM) workshops with six groups of professionals (total N
      = 42) from across health and social services sectors were undertaken. An online
      concept mapping consultation with 153 professionals was also conducted. In these
      CM activities, participants responded to the seeding statement "Thinking broadly
      from your experiences of working in the health system, what does an organisation
      need to have or do in order to enable communities and community members to fully
      engage with information and services to promote and maintain health and
      wellbeing". The CM data were analysed using multidimensional scaling and
      hierarchical cluster analyses to derive concept maps and cluster tree diagrams.
      Clusters from the CM processes were then integrated by identifying themes and
      subthemes across tree diagrams. RESULTS: Across the workshops, 373 statements
      were generated in response to the seeding statement. An additional 1206
      statements were generated in the online consultation. 84 clusters were derived
      within the workshops and 20 from the online consultation. Seven domains of health
      literacy responsiveness were identified; i) External policy and funding
      environment; ii) Leadership and culture; iii) Systems, processes and policies;
      iv) Access to services and programs; v) Community engagement and partnerships;
      vi) Communication practices and standards; and vii) Workforce. Each domain
      included 1 to 5 sub-domains (24 sub-domains in total). CONCLUSIONS: Using
      participatory research processes, a conceptual framework describing the
      characteristics, values, practices and capabilities of organisational health
      literacy responsiveness was derived. The framework may guide the planning and
      monitoring of health service and health system improvements, and has the
      potential to guide effective public health policy and health system reforms.

PMID- 28764700
TI  - Correlates of physical activity and sitting time in adults with type 2 diabetes
      attending primary health care in Oman.
AB  - BACKGROUND: Despite evidence of the benefits of physical activity in the
      management of type 2 diabetes, it is poorly addressed in diabetes care. This
      study aimed to identify the prevalence and correlates of meeting >=600MET-min/wk.
      (150 min/wk) of physical activity and sitting time in adults with type 2 diabetes
      in Oman. Approaches to encourage physical activity in diabetes care were
      explored. METHODS: A cross-sectional study using the Global Physical Activity
      Questionnaire was conducted in 17 randomly selected primary health centres in
      Muscat. Clinical data including co-morbidities were extracted from the health
      information system. Questions on physical activity preferences and approaches
      were included. Patients were approached if they were >=18 years, and had been
      registered in the diabetes clinic for >2 years. RESULTS: The questionnaire was
      completed by 305 people (females 57% and males 43%). Mean age (SD) was 57 (10.8)
      years and mean BMI (SD) was 31.0 (6.0) kg/m2. Duration of diabetes ranged from 2
      to 25 (mean 7.6) years. Hypertension (71%) and dyslipidaemia (62%) were common
      comorbidities. Most (58.4%) had an HbA1c >=7% indicating poor glycaemic control
      (55% in males vs 61% in females). Physical activity recommendations were met by
      21.6% of the participants, mainly through leisure activities. Odds of meeting the
      recommendations were significantly higher in males (OR 4.8, 95% CI 2.5-9.1),
      individuals <=57 years (OR 3.0, 95% CI 1.6-5.9), those at active self-reported
      stages of change for physical activity (OR 2.2, 95% CI 1.2-4.1) and those
      reporting no barriers to performing physical activity (OR 2.7, 95% CI 1.4-4.9).
      Median (25th, 75th percentiles) sitting time was 705 (600, 780) min/d. Older age
      (>57 years) was associated with longer sitting time (>705 min/d) (OR 2.8, 95% CI
      1.7-4.6). Preferred methods to support physical activity in routine diabetes care
      were consultations (38%), structured physical activity sessions (13.4%) and
      referrals to physical activity facilities (5.6%) delivered by a variety of health
      care providers. CONCLUSIONS: The results suggest that intervention strategies
      should take account of gender, age, opportunities within daily life to promote
      active behaviour and readiness to change. Offering physical activity
      consultations is of interest to this study population, thus development and
      evaluation of interventions are warranted.

PMID- 28764701
TI  - A versatile one-step CRISPR-Cas9 based approach to plasmid-curing.
AB  - BACKGROUND: Plasmids are widely used and essential tools in molecular biology.
      However, plasmids often impose a metabolic burden and are only temporarily useful
      for genetic engineering, bio-sensing and characterization purposes. While
      numerous techniques for genetic manipulation exist, a universal tool enabling
      rapid removal of plasmids from bacterial cells is lacking. RESULTS: Based on
      replicon abundance and sequence conservation analysis, we show that the vast
      majority of bacterial cloning and expression vectors share sequence similarities
      that allow for broad CRISPR-Cas9 targeting. We have constructed a universal
      plasmid-curing system (pFREE) and developed a one-step protocol and PCR procedure
      that allow for identification of plasmid-free clones within 24 h. While the
      context of the targeted replicons affects efficiency, we obtained curing
      efficiencies between 40 and 100% for the plasmids most widely used for expression
      and engineering purposes. By virtue of the CRISPR-Cas9 targeting, our platform is
      highly expandable and can be applied in a broad host context. We exemplify the
      wide applicability of our system in Gram-negative bacteria by demonstrating the
      successful application in both Escherichia coli and the promising cell factory
      chassis Pseudomonas putida. CONCLUSION: As a fast and freely available plasmid
      curing system, targeting virtually all vectors used for cloning and expression
      purposes, we believe that pFREE has the potential to eliminate the need for
      individualized vector suicide solutions in molecular biology. We envision the
      application of pFREE to be especially useful in methodologies involving multiple
      plasmids, used sequentially or simultaneously, which are becoming increasingly
      popular for genome editing or combinatorial pathway engineering.

PMID- 28764702
TI  - Characterisation of the correlation between standing lordosis and degenerative
      joint disease in the lower lumbar spine in women and men: a radiographic study.
AB  - BACKGROUND: Degenerative joint disease (DJD) in the lumbar spine is a common
      condition that is associated with chronic low back pain. Excessive loading of
      lumbar joints is a risk factor for DJD. Changes in lumbar lordosis significantly
      redistribute the forces of weight-bearing on the facet joints and the
      intervertebral discs. However, the relationship between lumbar lordosis and DJD
      has not been characterized in men and women. METHODS: We characterised the
      correlation between standing lumbar lordosis and DJD in standing radiographic
      images from 301 adult female and male chiropractic patients. DJD was rated using
      the Kellgren-Lawrence scale, and lordosis was measured using the Cobb angle.
      Linear and curvilinear correlations were investigated while controlling for age
      and sex. RESULTS: We found a highly significant curvilinear correlation between
      lordosis and DJD of the lower lumbar spine in both sexes, but especially in
      women, irrespective of the effects of age. We found the effect size of lordosis
      on lower lumbar DJD to be between 17.4 and 18.1% in women and 12.9% in older men.
      In addition, lordosis of 65 (95% CI 55.3-77.7) and 68 (98% CI 58.7-73.3) degrees
      were associated with minimal DJD in the lower lumbar spine of women and men
      respectively, and were therefore considered 'optimal'. This optimal lordotic
      angle was 73 (95% CI 58.8-87.2) degrees in older men. CONCLUSIONS: Both hypo- and
      hyper-lordosis correlate with DJD in the lumbar spine, particularly in women and
      in older men. These findings may well be of relevance to spinal pain management
      and spinal rehabilitation.

PMID- 28764703
TI  - Anti-tumor and anti-angiogenic effects of Fucoidan on prostate cancer: possible
      JAK-STAT3 pathway.
AB  - BACKGROUND: Prostate cancer is the most common cancer in men in the United
      States. Fucoidan is a bioactive polysaccharide extracted mainly from algae. The
      aim of this study was to investigate anti-tumor and anti-angiogenic effects of
      fucoidan in both cell-based assays and mouse xenograft model, as well as to
      clarify possible role of JAK-STAT3 pathway in the protection. METHODS: DU-145
      human prostate cancer cells were treated with 100-1000 MUg/mL of fucoidan. Cell
      viability, proliferation, migration and tube formation were studied using MTT,
      EdU, Transwell and Matrigel assays, respectively. Athymic nude mice were
      subcutaneously injected with DU-145 cells to induce xenograft model, and treated
      by oral gavage with 20 mg/kg of fucoidan for 28 days. Tumor volume and weight
      were recorded. Vascular density in tumor tissue was determined by hemoglobin
      assay and endothelium biomarker analysis. Protein expression and phosphorylation
      of JAK and STAT3 were determined by Western blot. Activation of gene promoters
      was investigated by chromatin Immunoprecipitation. RESULTS: Fucoidan could dose
      dependently inhibit cell viability and proliferation of DU-145 cells. Besides,
      fucoidan also inhibited cell migration in Transwell and tube formation in
      Matrigel. In animal study, 28-day treatment of fucoidan significantly hindered
      the tumor growth and inhibited angiogenesis, with decreased hemoglobin content
      and reduced mRNA expression of CD31 and CD105 in tumor tissue. Furthermore,
      phosphorylated JAK and STAT3 in tumor tissue were both reduced after fucoidan
      treatment, and promoter activation of STAT3-regulated genes, such as VEGF, Bcl-xL
      and Cyclin D1, was also significantly reduced after treatment. CONCLUSIONS: All
      these findings provided novel complementary and alternative strategies to treat
      prostate cancer.

PMID- 28764704
TI  - Objective impairments of gait and balance in adults living with HIV-1 infection:
      a systematic review and meta-analysis of observational studies.
AB  - BACKGROUND: Gait and balance deficits are reported in adults with HIV infection
      and are associated with reduced quality of life. Current research suggests an
      increased fall-incidence in this population, with fall rates among middle-aged
      adults with HIV approximating that in seronegative elderly populations. Gait and
      postural balance rely on a complex interaction of the motor system, sensory
      control, and cognitive function. However, due to disease progression and
      complications related to ongoing inflammation, these systems may be compromised
      in people with HIV. Consequently, locomotor impairments may result that can
      contribute to higher-than-expected fall rates. The aim of this review was to
      synthesize the evidence regarding objective gait and balance impairments in
      adults with HIV, and to emphasize those which could contribute to increased fall
      risk. METHODS: This review followed the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search of published
      observational studies was conducted in March 2016. Methodological quality was
      assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross
      Sectional Studies. Narrative synthesis of gait and balance outcomes was
      performed, and meta-analyses where possible. RESULTS: Seventeen studies were
      included, with fair to low methodological quality. All studies used clinical
      tests for gait-assessment. Gait outcomes assessed were speed, initiation-time and
      cadence. No studies assessed kinetics or kinematics. Balance was assessed using
      both instrumented and clinical tests. Outcomes were mainly related to center of
      pressure, postural reflex latencies, and timed clinical tests. There is some
      agreement that adults with HIV walk slower and have increased center of pressure
      excursions and -long loop postural reflex latencies, particularly under
      challenging conditions. CONCLUSIONS: Gait and balance impairments exist in people
      with HIV, resembling fall-associated parameters in the elderly. Impairments are
      more pronounced during challenging conditions, might be associated with disease
      severity, are not influenced by antiretroviral therapy, and might not be
      associated with peripheral neuropathy. Results should be interpreted cautiously
      due to overall poor methodological quality and heterogeneity. Locomotor
      impairments in adults with HIV are currently insufficiently quantified. Future
      research involving more methodological uniformity is warranted to better
      understand such impairments and to inform clinical decision-making, including
      fall-prevention strategies, in this population.

PMID- 28764705
TI  - Drug survival of second biological DMARD therapy in patients with rheumatoid
      arthritis: a retrospective non-interventional cohort analysis.
AB  - BACKGROUND: Since persistence to first biological disease modifying anti
      rheumatic drugs (bDMARDs) is far from ideal in rheumatoid arthritis (RA)
      patients, many do receive a second and/or third bDMARD treatment. However, little
      is known about treatment persistence of the second-line bDMARD and it is
      specifically unknown whether the mode of action of such a treatment is associated
      with different persistence rates. We aimed to assess discontinuation-, re
      initiation- or continuation-rates of a 2nd bDMARD therapy as well as switching
      rates to a third biological DMARD (3rd bDMARD) therapy in RA patients. METHOD:
      Analysis was based on German claims data (2010-2013). Patients were included if
      they had received at least one prescription for an anti-TNF and at least one
      follow-up prescription of a 2nd bDMARD different from the first anti-TNF. Patient
      follow-up started on the date of the first prescription for the 2nd bDMARD and
      lasted for 12 months or until a patient's death. RESULTS: 2667 RA patients
      received at least one anti-TNF prescription. Of these, 451 patients received a
      second bDMARD (340 anti-TNF, mean age 52.6 years; 111 non-anti-TNF, mean age 55.9
      years). During the follow-up, 28.8% vs. 11.7% of the 2nd anti-TNF vs. non-anti
      TNF patients (p < 0.001) switched to a 3rd bDMARD; 14.1% vs. 19.8% (p = 0.179)
      discontinued without re-start; 3.8% vs.1.8% (p = 0.387) re-started and 53.5 vs.
      66.7% (p < 0.050) continued therapy. Patients in the non-anti-TNF group
      demonstrated longer drug survival (295 days) than patients in the anti-TNF group
      (264 days; p = 0.016). Independent variables associated with earlier
      discontinuation (including re-start) or switch were prescription of an anti-TNF
      as 2nd bDMARD (HR = 1.512) and a higher comorbidity level (CCI, HR = 1.112),
      whereas previous painkiller medication (HR = 0.629) was associated with later
      discontinuation or switch. CONCLUSIONS: Only 56.8% of RA patients continued 2nd
      bDMARD treatment after 12 months; 60% if re-start was included. Non-anti-TNF
      patients had a higher probability of continuing 2nd bDMARD therapy.

PMID- 28764706
TI  - Is the medical financial assistance program an effective supplement to social
      health insurance for low-income households in China? A cross-sectional study.
AB  - BACKGROUND: China uses both social health insurance (SHI) programs and a medical
      financial assistance (MFA) program to protect the poor from illness-induced
      financial risks. The MFA provides a dual benefit package targeting low-income
      families: subsidizing these families' participation in SHI programs, and
      providing cash aid to protect them from catastrophic health expenditure (CHE).
      This study aims to investigate: (1) the association between MFA subvention for
      SHI enrollment and SHI enrollment; (2) the association between MFA cash aid and
      CHE; and (3) the association between SHI enrollment and CHE in low-income
      households in China. METHODS: Using nationally representative data from a
      comprehensive survey of low-income households in 2014, we construct an estimate
      of CHE based on out-of-pocket health spending data. Controlling for other
      covariates, we estimate the three associations using a three-level logistic
      model. RESULTS: The MFA program subsidizes 50.1% of low-income households to aid
      their enrollment in SHI programs and provides cash aid to 24.1% of these
      households. Multilevel logistic analysis reveals that MFA subvention has no
      significant association with low-income households' SHI enrollment, that MFA cash
      aid has no significant association with CHE, and that full SHI enrollment is
      inversely associated with CHE status. CONCLUSIONS: The MFA program is currently
      not an effective supplement to SHI programs in China in terms of promoting SHI
      enrollment and providing financial risk protection. The Chinese government needs
      to invest more funds to expand further low-income household enrollment in SHI
      programs and to widen the benefit package of MFA cash aid.

PMID- 28764707
TI  - Delayed anastomotic leakage following laparoscopic intersphincteric resection for
      lower rectal cancer: report of four cases and literature review.
AB  - BACKGROUND: Anastomotic leakage (AL) is one of the most dreadful postoperative
      complications because it can result in increased morbidity and mortality as well
      as poorer long-term prognosis. Although most studies of AL limited their
      investigation time to a period of 30 days postoperatively, only a few studies
      have shown that AL can occur after that period. Here, we report four patients of
      rectal cancer with delayed AL following laparoscopic intersphincteric resection
      (ISR) and conduct a literature review on delayed AL. CASE PRESENTATION: Case 1
      was a 67-year-old male who underwent laparoscopic partial ISR in July 2009.
      Although the patient was asymptomatic, an anastomotic-urethral fistula was
      observed 57 months after ISR. Case 2 was a 44-year-old female who underwent
      laparoscopic partial ISR in July 2008. She presented with discharge of gas and
      feces from her vagina, and an anastomotic-vaginal fistula was observed 14 months
      after ISR. Case 3 was a 74-year-old man who underwent laparoscopic partial ISR in
      August 2007. He presented with pneumaturia and fecaluria, and an anastomotic
      urethral fistula was observed 4 months after ISR. Case 4 was a 68-year-old woman
      who underwent laparoscopic subtotal ISR for rectal cancer in February 2013 and
      partial hepatic resection for liver metastases in March 2013. She presented with
      anal pain and purulent perineal discharge, and an anastomotic-perineal fistula
      was observed 9 months after ISR. All four cases presented with fistula formation
      and required reoperation (establishment of a diverting ileostomy). CONCLUSIONS:
      Since delayed AL is not a rare postoperative complication, surgeons need to
      provide long-term follow-up and remain alert to the possible development of
      delayed AL.

PMID- 28764708
TI  - Estimating the survival advantage based on telomere length and serum biomarkers
      of aging.
AB  - BACKGROUND: This study aimed to establish a model that estimates the survival
      advantage at the molecular level based on telomere length and serum biomarkers of
      aging, to explore clinical significance. METHODS: The study consisted of 100
      healthy subjects and 40 type 2 diabetes mellitus patients, 20-90 years of age.
      Saliva telomere relative length (LnTL) was measured by the quantitative real-time
      polymerase chain reaction and the serum biochemical parameters, including albumin
      (ALB), total proteins, total cholesterol, triglycerides, and some enzyme
      parameters were detected by a biochemical analyzer. The Z values were transformed
      from mean values and standard deviations to estimate the survival advantage. A
      normal reference range (95% confidence interval) was set to the comprehensive
      advantage of the Z values (Zs) to evaluate the comprehensive survival advantage.
      RESULTS: The Z values of serum ALB and saliva LnTL could be used to estimate the
      survival advantage, and effectively distinguish between the aging and nonaging
      individuals. The Zs was greater than 1.64 in the normal reference range, and type
      2 diabetes mellitus patients had lower survival advantages compared to those of
      the control group (p < 0.05). CONCLUSIONS: Our two-dimensional model system using
      ALB and LnTL was valid and may have potential applications for evaluating the
      aging status at the molecular level, and for the observation of disease
      characteristics.

PMID- 28764709
TI  - Antibody responses to two new Lactococcus lactis-produced recombinant Pfs48/45
      and Pfs230 proteins increase with age in malaria patients living in the Central
      Region of Ghana.
AB  - BACKGROUND: Recent advances in malaria control efforts have led to an increased
      number of national malaria control programmes implementing pre-elimination
      measures and demonstrated the need to develop new tools to track and control
      malaria transmission. Key to understanding transmission is monitoring the
      prevalence and immune response against the sexual stages of the parasite, known
      as gametocytes, which are responsible for transmission. Sexual-stage specific
      antigens, Pfs230 and Pfs48/45, have been identified and shown to be targets for
      transmission blocking antibodies, but they have been difficult to produce
      recombinantly in the absence of a fusion partner. METHODS: Regions of Pfs48/45
      and Pfs230 known to contain transmission blocking epitopes, 6C and C0,
      respectively, were produced in a Lactococcus lactis expression system and used in
      enzyme linked immunosorbent assays to determine the seroreactivity of 95 malaria
      patients living in the Central Region of Ghana. RESULTS: Pfs48/45.6C and
      Pfs230.C0 were successfully produced in L. lactis in the absence of a fusion
      partner using a simplified purification scheme. Seroprevalence for L. lactis
      produced Pfs48/45.6C and Pfs230.C0 in the study population was 74.7 and 72.8%,
      respectively. CONCLUSIONS: A significant age-dependent increase in antibody
      titers was observed, which suggests a vaccine targeting these antigens could be
      boosted during a natural infection in the field.

PMID- 28764711
TI  - Video-tactile pneumatic sensor for soft tissue elastic modulus estimation.
AB  - BACKGROUND: A new sensor for estimating elasticity of soft tissues such as a
      liver was developed for minimally invasive surgery application. METHODS: By
      measuring deformation and adjusting internal pressure of the pneumatic sensor
      head, the sensor can be used to do palpation (indentation) of tissues with wide
      range of stiffness. A video camera installed within the sensor shell is used to
      register the radius of the contact area. Based on finite element model
      simulations and the measured data, elastic modulus of the indented soft tissue
      can be calculated. RESULTS AND CONCLUSIONS: Three phantom materials, namely
      plastic, silicone and gelatin, with varied stiffness were tested. The
      experimental results demonstrated that the new sensor can obtain highly reliable
      data with error less than 5%. The new sensor might be served as an instrument in
      laparoscopic surgery for diagnosis of pathological tissues or internal organs.

PMID- 28764710
TI  - Host attraction and biting behaviour of Anopheles mosquitoes in South Halmahera,
      Indonesia.
AB  - BACKGROUND: Indonesia is home to a variety of malaria vectors whose specific
      bionomic traits remain largely uncharacterized. Species-specific behaviours, such
      as host feeding preferences, impact the dynamics of malaria transmission and the
      effectiveness of vector control interventions. METHODS: To examine species
      specific host attraction and feeding behaviours, a Latin square design was used
      to compare Anopheles mosquitoes attracted to human, cow, and goat-baited tents.
      Anopheles mosquitoes were collected hourly from the inside walls of each baited
      tent. Species were morphologically and then molecularly identified using rDNA
      ITS2 sequences. The head and thorax of individual specimens were analysed for
      Plasmodium DNA using PCR. Bloodmeals were identified using a multiplex PCR.
      RESULTS: A total of 1024, 137, and 74 Anopheles were collected over 12 nights in
      cow, goat, and human-baited tents, respectively. The species were identified as
      Anopheles kochi, Anopheles farauti s.s., Anopheles hackeri, Anopheles hinesorum,
      Anopheles indefinitus, Anopheles punctulatus, Anopheles tessellatus, Anopheles
      vagus, and Anopheles vanus, many of which are known to transmit human malaria.
      Molecular analysis of blood meals revealed a high level of feeding on multiple
      host species in a single night. Anopheles kochi, An. indefinitus, and An. vanus
      were infected with Plasmodium vivax at rates comparable to primary malaria
      vectors. CONCLUSIONS: The species distributions of Anopheles mosquitoes attracted
      to human, goat, and cow hosts were similar. Eight of nine sporozoite positive
      samples were captured with animal-baited traps, indicating that even
      predominantly zoophilic mosquitoes may be contributing to malaria transmission.
      Multiple host feeding and flexibility in blood feeding behaviour have important
      implications for malaria transmission, malaria control, and the effectiveness of
      intervention and monitoring methods, particularly those that target human-feeding
      vectors.

PMID- 28764712
TI  - Sclerosing mesenteritis mimicking metachronous peritoneal metastases from
      descending colon adenocarcinoma.
AB  - BACKGROUND: Sclerosing mesenteritis is a non-neoplastic inflammatory disease that
      occurs in the bowel mesentery. Distinguishing sclerosing mesenteritis from
      neoplasms may be difficult because of the clinical and radiographic similarities
      between the two disease entities. CASE PRESENTATION: We report a case of
      sclerosing mesenteritis mimicking peritoneal metastases of colorectal carcinoma.
      A 73-year-old man with stage II descending colon adenocarcinoma with poor
      prognostic features was found to have developed left lower abdominal quadrant
      masses on computed tomography (CT) 9 months after undergoing radical surgery.
      These masses were diagnosed as peritoneal metastases because they grew in size
      and displayed fluorodeoxyglucose (FDG) uptake 3 months later; thus, a laparotomy
      was performed. The masses, which were localized in the jejunal mesentery, were
      excised completely via segmental jejunal resection. Histopathological analysis
      confirmed that the masses were sclerosing mesenteritis. The patient showed no
      signs of sclerosing mesenteritis or colorectal carcinoma recurrence during follow
      up. CONCLUSIONS: In patients suspected of having localized peritoneal metastasis
      from malignancies, any masses must be sampled by surgical excisional biopsy and
      subsequently examined to rule out alternative diagnoses, such as sclerosing
      mesenteritis.

PMID- 28764713
TI  - Non-iterative geometric approach for inverse kinematics of redundant lead-module
      in a radiosurgical snake-like robot.
AB  - BACKGROUND: Snake-like robot is an emerging form of serial-link manipulator with
      the morphologic design of biological snakes. The redundant robot can be used to
      assist medical experts in accessing internal organs with minimal or no invasion.
      Several snake-like robotic designs have been proposed for minimal invasive
      surgery, however, the few that were developed are yet to be fully explored for
      clinical procedures. This is due to lack of capability for full-fledged spatial
      navigation. In rare cases where such snake-like designs are spatially flexible,
      there exists no inverse kinematics (IK) solution with both precise control and
      fast response. METHODS: In this study, we proposed a non-iterative geometric
      method for solving IK of lead-module of a snake-like robot designed for therapy
      or ablation of abdominal tumors. The proposed method is aimed at providing
      accurate and fast IK solution for given target points in the robot's workspace. n
      1 virtual points (VPs) were geometrically computed and set as coordinates of
      intermediary joints in an n-link module. Suitable joint angles that can place the
      end-effector at given target points were then computed by vectorizing coordinates
      of the VPs, in addition to coordinates of the base point, target point, and tip
      of the first link in its default pose. The proposed method is applied to solve IK
      of two-link and redundant four-link modules. RESULTS: Both two-link and four-link
      modules were simulated with Robotics Toolbox in Matlab 8.3 (R2014a).
      Implementation result shows that the proposed method can solve IK of the
      spatially flexible robot with minimal error values. Furthermore, analyses of
      results from both modules show that the geometric method can reach 99.21 and
      88.61% of points in their workspaces, respectively, with an error threshold of 1
      mm. The proposed method is non-iterative and has a maximum execution time of
      0.009 s. CONCLUSIONS: This paper focuses on solving IK problem of a spatially
      flexible robot which is part of a developmental project for abdominal surgery
      through minimal invasion or natural orifices. The study showed that the proposed
      geometric method can resolve IK of the snake-like robot with negligible error
      offset. Evaluation against well-known methods shows that the proposed method can
      reach several points in the robot's workspace with high accuracy and shorter
      computational time, simultaneously.

PMID- 28764714
TI  - Testis specific histone 2B is associated with sperm chromatin dynamics and bull
      fertility-a pilot study.
AB  - BACKGROUND: Bull fertility is the degree of sperm's ability to fertilize and
      activate the egg and support embryo development, and this is critical for herd
      reproductive performance. We used the bull as a unique model organism for the
      study of male fertility because cattle genetics and physiology is similar to
      those of other mammals including humans. Moreover, reliable fertility data along
      with well-established in vitro systems are available for bovine. The objective of
      this original study was to ascertain evolutionary diversification and expression
      dynamics of Testis Specific Histone 2B (TH2B) in sperm from Holstein bulls with
      different fertility scores. METHODS: The intensity of TH2B was determined by
      using flow cytometry in sperm from 13 high and 13 low fertility bulls. Expression
      levels of TH2B were measured using immunofluorescence and Western blotting in
      sperm from five high and five low fertility bulls. Sequence identity,
      evolutionary distance and interactome of TH2B were evaluated by dotmatcher,
      STRING and Cytoscape. Data were analyzed using linear mixed effects model and
      regression plots were drawn. RESULTS: The intensity of TH2B as measured by flow
      cytometry was significantly affected by an interaction between fertility group
      and fertility score (P = 0.0182). The intensity of TH2B in sperm from the high
      fertility group decreased (P = 0.0055) as fertility increased. TH2B was
      constantly detectable in sperm and expression levels of TH2B decreased in
      relation to fertility in sperm from the high fertility group (P = 0.018). TH2B
      biological functions include male gamete generation, chromosome organization, DNA
      packaging, DNA conformation change, chromatin organization, nucleosome
      organization, chromatin disassembly, spermatid nucleus elongation, spermatid
      nucleus differentiation, sperm motility, chromatin organization, chromatin
      condensation, chromatin silencing, nucleus organization, and chromatin remodeling
      (P < 0.05). CONCLUSIONS: We elucidated the cellular localization and molecular
      physiology of TH2B using both computational and cell biology approaches. In
      addition to advancing the fundamental science of mammalian male gamete, the
      present findings can be potentially used to evaluate semen quality and predict
      male fertility in the future. TRIAL REGISTRATION: This study did not involve any
      live animals. We did not perform any anesthesia, euthanasia, or any kind of
      animal sacrifice. The cryopreserved semen samples were obtained from Alta
      Genetics, Inc., Watertown, WI, USA. All samples were preserved in liquid
      nitrogen.

PMID- 28764715
TI  - Comparison between micro- and nanosized copper oxide and water soluble copper
      chloride: interrelationship between intracellular copper concentrations,
      oxidative stress and DNA damage response in human lung cells.
AB  - BACKGROUND: Nano- and microscale copper oxide particles (CuO NP, CuO MP) are
      applied for manifold purposes, enhancing exposure and thus the potential risk of
      adverse health effects. Based on the pronounced in vitro cytotoxicity of CuO NP,
      systematic investigations on the mode of action are required. Therefore, the
      impact of CuO NP, CuO MP and CuCl2 on the DNA damage response on transcriptional
      level was investigated by quantitative gene expression profiling via high
      throughput RT-qPCR. Cytotoxicity, copper uptake and the impact on the oxidative
      stress response, cell cycle regulation and apoptosis were further analysed on the
      functional level. RESULTS: Cytotoxicity of CuO NP was more pronounced when
      compared to CuO MP and CuCl2 in human bronchial epithelial BEAS-2B cells. Uptake
      studies revealed an intracellular copper overload in the soluble fractions of
      both cytoplasm and nucleus, reaching up to millimolar concentrations in case of
      CuO NP and considerably lower levels in case of CuO MP and CuCl2. Moreover, CuCl2
      caused copper accumulation in the nucleus only at cytotoxic concentrations. Gene
      expression analysis in BEAS-2B and A549 cells revealed a strong induction of
      uptake-related metallothionein genes, oxidative stress-sensitive and pro
      inflammatory genes, anti-oxidative defense-associated genes as well as those
      coding for the cell cycle inhibitor p21 and the pro-apoptotic Noxa and DR5. While
      DNA damage inducible genes were activated, genes coding for distinct DNA repair
      factors were down-regulated. Modulation of gene expression was most pronounced in
      case of CuO NP as compared to CuO MP and CuCl2 and more distinct in BEAS-2B
      cells. GSH depletion and activation of Nrf2 in HeLa S3 cells confirmed oxidative
      stress induction, mainly restricted to CuO NP. Also, cell cycle arrest and
      apoptosis induction were most distinct for CuO NP. CONCLUSIONS: The high
      cytotoxicity and marked impact on gene expression by CuO NP can be ascribed to
      the strong intracellular copper ion release, with subsequent copper accumulation
      in the cytoplasm and the nucleus. Modulation of gene expression by CuO NP
      appeared to be primarily oxidative stress-related and was more pronounced in
      redox-sensitive BEAS-2B cells. Regarding CuCl2, relevant modulations of gene
      expression were restricted to cytotoxic concentrations provoking impaired copper
      homoeostasis.

PMID- 28764716
TI  - Generation of transgenic rodent malaria parasites by transfection of cell culture
      derived merozoites.
AB  - BACKGROUND: Malaria research is greatly dependent on and has drastically advanced
      with the possibility of genetically modifying Plasmodium parasites. The commonly
      used transfection protocol by Janse and colleagues utilizes blood stage-derived
      Plasmodium berghei schizonts that have been purified from a blood culture by
      density gradient centrifugation. Naturally, this transfection protocol depends on
      the availability of suitably infected mice, constituting a time-based variable.
      In this study, the potential of transfecting liver stage-derived merozoites was
      explored. In cell culture, upon merozoite development, infected cells detach from
      the neighbouring cells and can be easily harvested from the cell culture
      supernatant. This protocol offers robust experimental timing and temporal
      flexibility. METHODS: HeLa cells are infected with P. berghei sporozoites to
      obtain liver stage-derived merozoites, which are harvested from the cell culture
      supernatant and are transfected using the Amaxa Nucleofector(r) electroporation
      technology. RESULTS: Using this protocol, wild type P. berghei ANKA strain and
      marker-free PbmCherryHsp70-expressing P. berghei parasites were successfully
      transfected with DNA constructs designed for integration via single- or double
      crossover homologous recombination. CONCLUSION: An alternative protocol for
      Plasmodium transfection is hereby provided, which uses liver stage-derived P.
      berghei merozoites for transfection. This protocol has the potential to
      substantially reduce the number of mice used per transfection, as well as to
      increase the temporal flexibility and robustness of performing transfections, if
      mosquitoes are routinely present in the laboratory. Transfection of liver stage
      derived P. berghei parasites should enable generation of transgenic parasites
      within 8-18 days.

PMID- 28764717
TI  - A longitudinal cohort study of malaria exposure and changing serostatus in a
      malaria endemic area of rural Tanzania.
AB  - BACKGROUND: Measurements of anti-malarial antibodies are increasingly used as a
      proxy of transmission intensity. Most serological surveys are based on the use of
      cross-sectional data that, when age-stratified, approximates historical patterns
      of transmission within a population. Comparatively few studies leverage
      longitudinal data to explicitly relate individual infection events with
      subsequent antibody responses. METHODS: The occurrence of seroconversion and
      seroreversion events for two Plasmodium falciparum asexual stage antigens (MSP-1
      and AMA-1) was examined using three annual measurements of 691 individuals from a
      cohort of individuals in a malaria-endemic area of rural east-central Tanzania.
      Mixed-effect logistic regression models were employed to determine factors
      associated with changes in serostatus over time. RESULTS: While the expected
      population-level relationship between seroprevalence and disease incidence was
      observed, on an individual level the relationship between individual infections
      and the antibody response was complex. MSP-1 antibody responses were more dynamic
      in response to the occurrence and resolution of infection events than AMA-1,
      while the latter was more correlated with consecutive infections. The MSP-1
      antibody response to an observed infection seemed to decay faster over time than
      the corresponding AMA-1 response. Surprisingly, there was no evidence of an age
      effect on the occurrence of a conversion or reversion event. CONCLUSIONS: While
      the population-level results concur with previously published sero
      epidemiological surveys, the individual-level results highlight the more complex
      relationship between detected infections and antibody dynamics than can be
      analysed using cross-sectional data. The longitudinal analysis of serological
      data may provide a powerful tool for teasing apart the complex relationship
      between infection events and the corresponding immune response, thereby improving
      the ability to rapidly assess the success or failure of malaria control
      programmes.

PMID- 28764718
TI  - Comparative analysis of the EGFR, HER2, c-MYC, and MET variations in colorectal
      cancer determined by three different measures: gene copy number gain,
      amplification status and the 2013 ASCO/CAP guideline criterion for HER2 testing
      of breast cancer.
AB  - BACKGROUND: The purpose of this study was to explore gene copy number (GCN)
      variation of EGFR, HER2, c-MYC, and MET in patients with primary colorectal
      cancer (CRC). METHODS: Dual-colour silver-enhanced in situ hybridization was
      performed in tissue samples of 334 primary CRC patients. The amplification status
      (GCN ratio >=2) and GCN gain (average GCN >=4) data for the EGFR, HER2, c-MYC and
      MET genes were obtained. GCN variation was also assessed by the criterion of the
      2013 ASCO/CAP guidelines for HER2 testing. RESULTS: Amplification of EGFR, HER2,
      c-MYC and MET was detected in 8 (2.4%), 20 (6.0%), 29 (8.7%), and 14 (4.2%)
      patients, respectively. Of 66 patients with at least one amplified gene, five
      exhibited co-amplification of genes studied (HER2-MET co-amplification: two
      patients; HER2-c-MYC co-amplification: two patients; EGFR-c-MYC co-amplification:
      one patient). There were 109 patients with GCN gains of one or more genes (EGFR:
      11/334, HER2: 29/334, c-MYC; 60/334, MET: 48/334) and 32.1% (35/109) had multiple
      GCN gains. When each GCN was assessed by the criterion of the ASCO/CAP 2013
      guideline for HER2 testing, 116 people showed positive or equivocal results for
      one or more genes. The cumulative amplification status had no association with
      patients' outcome. However, the cumulative results of the GCN gain and GCN status
      determined according to the ASCO/CAP guideline had a significant prognostic
      correlation in the univariate analysis (P values of 0.006 and 0.022,
      respectively). In the multivariate analysis, GCN gain and GCN status were
      independent prognostic factors (P values of 0.010 and 0.017, respectively).
      CONCLUSIONS: In this study, we evaluated GCN variation of four genes in a large
      sample of Korean CRC patients. The amplification status was not related to
      patient outcome. However, the GCN gain and GCN status according to the ASCO/CAP
      2013 guideline were independent prognostic factors.

PMID- 28764719
TI  - A combination of HPLC and automated data analysis for monitoring the efficiency
      of high-pressure homogenization.
AB  - BACKGROUND: Cell disruption is a key unit operation to make valuable,
      intracellular target products accessible for further downstream unit operations.
      Independent of the applied cell disruption method, each cell disruption process
      must be evaluated with respect to disruption efficiency and potential product
      loss. Current state-of-the-art methods, like measuring the total amount of
      released protein and plating-out assays, are usually time-delayed and involve
      manual intervention making them error-prone. An automated method to monitor cell
      disruption efficiency at-line is not available to date. RESULTS: In the current
      study we implemented a methodology, which we had originally developed to monitor
      E. coli cell integrity during bioreactor cultivations, to automatically monitor
      and evaluate cell disruption of a recombinant E. coli strain by high-pressure
      homogenization. We compared our tool with a library of state-of-the-art methods,
      analyzed the effect of freezing the biomass before high-pressure homogenization
      and finally investigated this unit operation in more detail by a multivariate
      approach. CONCLUSION: A combination of HPLC and automated data analysis describes
      a valuable, novel tool to monitor and evaluate cell disruption processes. Our
      methodology, which can be used both in upstream (USP) and downstream processing
      (DSP), describes a valuable tool to evaluate cell disruption processes as it can
      be implemented at-line, gives results within minutes after sampling and does not
      need manual intervention.

PMID- 28764720
TI  - Setting performance-based financing in the health sector agenda: a case study in
      Cameroon.
AB  - BACKGROUND: More than 30 countries in sub-Saharan Africa have introduced
      performance-based financing (PBF) in their healthcare systems. Yet, there has
      been little research on the process by which PBF was put on the national policy
      agenda in Africa. This study examines the policy process behind the introduction
      of PBF program in Cameroon. METHODS: The research is an explanatory case study
      using the Kingdon multiple streams framework. We conducted a document review and
      25 interviews with various types of actors involved in the policy process. We
      conducted thematic analysis using a hybrid deductive-inductive approach for data
      analysis. RESULTS: By 2004, several reports and events had provided evidence on
      the state of the poor health outcomes and health financing in the country,
      thereby raising awareness of the situation. As a result, decision-makers
      identified the lack of a suitable health financing policy as an important issue
      that needed to be addressed. The change in the political discourse toward more
      accountability made room to test new mechanisms. A group of policy entrepreneurs
      from the World Bank, through numerous forms of influence (financial, ideational,
      network and knowledge-based) and building on several ongoing reforms,
      collaborated with senior government officials to place the PBF program on the
      agenda. The policy changes occurred as the result of two open policy windows
      (i.e. national and international), and in both instances, policy entrepreneurs
      were able to couple the policy streams to effect change. CONCLUSION: The policy
      agenda of PBF in Cameroon underlined the importance of a perceived crisis in the
      policy reform process and the advantage of building a team to carry forward the
      policy process. It also highlighted the role of other sources of information
      alongside scientific evidence (eg.: workshop and study tour), as well as the role
      of previous policies and experiences, in shaping or influencing respectively the
      way issues are framed and reformers' actions and choices.

PMID- 28764721
TI  - What is the gap in activity and participation between people with disability and
      the general population in Taiwan?
AB  - BACKGROUND: In 2010, the World Health Organization Disability Assessment Schedule
      2.0 (WHODAS 2.0) was developed, based on the concept of the International
      Classification of Functioning, Disability and Health (ICF). The ICF provides a
      common language and framework for health and health-related status and attempts
      to integrate the biopsychosocial model as a multidimensional perspective in
      understanding functioning. Activities and participation (AP) is one salient
      component of the ICF refers to the execution of a task by an individual, and how
      such tasks are involved in their daily life. It is essential to examine the gap
      between the general adult population and adults with disabilities. This gap may
      be attributed to health status, personal factors, and natural and social
      environments, which include social and health services and policies. The
      purposes: (1) To develop a normative activity and participation (AP) value for
      the adult population and people with disabilities; and (2) to compare the gap in
      AP normative values between the two groups in Taiwan. METHODS: We use the WHODAS
      2.0 to survey and develop a normative AP value for the general adult population,
      and used secondary data from National Disability Eligibility Determination System
      (NDEDS) of Taiwan to describe the AP functioning distribution of adult with
      disability. There were 1100 participants, selected by stratified proportional
      sampling from two cities. There were also 144,850 participants who were adults
      with disability, selected from the secondary database in Taiwan. RESULTS AND
      CONCLUSIONS: The AP curve for the disabled population increased rapidly at the
      beginning. The summary score was 13.21 in the performance at 90 percentile for
      the general population and 82.61 score for disabled adults that the similar gap
      in every domain, its means that there are significant functioning difference and
      health equality in general adults population and adults with disabilities. This
      presents a substantial challenge for both the government and the whole population
      of Taiwan, to begin considering how to reduce the gap in AP functioning and
      promote equality for people with disabilities, using social welfare policy. It is
      important to make sure disabled people have the same rights to be included in
      society as anybody else and better access to things in all areas of life that are
      according to Convention on the Rights of Persons with Disabilities (CRPD).

PMID- 28764722
TI  - A web-based, patient driven registry for Angelman syndrome: the global Angelman
      syndrome registry.
AB  - Angelman syndrome (AS) is a rare neurodevelopmental disorder that is
      characterised by severe global developmental delays, ataxia, loss of speech,
      epilepsy, sleep disorders, and a happy disposition. There is currently no cure
      for AS, though several pharmaceutical companies are anticipating drug trials for
      new therapies to treat AS. The Foundation for Angelman Therapeutics (FAST)
      Australia therefore identified a need for a global AS patient registry to
      identify patients for recruitment for clinical trials.The Global AS Registry was
      deployed in September 2016 utilising the Rare Disease Registry Framework, an open
      source tool that enables the efficient creation and management of patient
      registries. The Global AS Registry is web-based and allows parents and guardians
      worldwide to register, provide informed consent, and enter data on individuals
      with AS. 286 patients have registered in the first 8 months since deployment.We
      demonstrate the successful deployment of the first patient-driven global registry
      for AS. The data generated from the Global AS Registry will be crucial in
      identifying patients suitable for clinical trials and in informing research that
      will identify treatments for AS, and ultimately improve the lives of individuals
      and their families living with AS.

PMID- 28764723
TI  - Systematic review on traditional medicinal plants used for the treatment of
      malaria in Ethiopia: trends and perspectives.
AB  - BACKGROUND: Ethiopia is endowed with abundant medicinal plant resources and
      traditional medicinal practices. However, available research evidence on
      indigenous anti-malarial plants is highly fragmented in the country. The present
      systematic review attempted to explore, synthesize and compile ethno-medicinal
      research evidence on anti-malarial medicinal plants in Ethiopia. METHODS: A
      systematic web search analysis and review was conducted on research literature
      pertaining to medicinal plants used for traditional malaria treatment in
      Ethiopia. Data were collected from a total of 82 Ethiopian studies meeting
      specific inclusion criteria including published research articles and unpublished
      thesis reports. SPSS Version 16 was used to summarize relevant ethno
      botanical/medicinal information using descriptive statistics, frequency,
      percentage, tables, and bar graphs. RESULTS: A total of 200 different plant
      species (from 71 families) used for traditional malaria treatment were identified
      in different parts of Ethiopia. Distribution and usage pattern of anti-malarial
      plants showed substantial variability across different geographic settings. A
      higher diversity of anti-malarial plants was reported from western and
      southwestern parts of the country. Analysis of ethno-medicinal recipes indicated
      that mainly fresh leaves were used for preparation of remedies. Decoction,
      concoction and eating/chewing were found to be the most frequently employed
      herbal remedy preparation methods. Notably, anti-malarial herbal remedies were
      administered by oral route. Information on potential side effects of anti
      malarial herbal preparations was patchy. However, some anti-malarial plants were
      reported to have potentially serious side effects using different local antidotes
      and some specific contra-indications. CONCLUSION: The study highlighted a rich
      diversity of indigenous anti-malarial medicinal plants with equally divergent
      herbal remedy preparation and use pattern in Ethiopia. Baseline information gaps
      were observed in key geographic settings. Likewise, herbal remedy toxicity risks
      and countermeasures generally entailed more exhaustive investigation.
      Experimental research and advanced chemical analysis are also required to
      validate the therapeutic potential of anti-malarial compounds from promising
      plant species.

PMID- 28764724
TI  - Pre-event quality of life and its influence on the post-event quality of life
      among patients with ST elevation and non-ST elevation myocardial infarctions of a
      premier province of Sri Lanka.
AB  - BACKGROUND: Pre-event Quality of Life (QOL) reflects the true social
      circumstances in which people live prior to the onset of myocardial infarctions.
      It is believed to be a predictor of the post-event QOL. The aim of this study was
      to describe the pre-event QOL and its influence on the post-event Quality of Life
      among patients with ST elevation (STEMI) and Non-ST elevation myocardial
      infarctions (NSTEMI) using Short Form-36 (SF-36), a generic QOL tool with 8
      domains. Documented literature is rare in this regard in Sri Lanka, which is a
      lower-middle-income country. METHODS: A cross-sectional study with a 28-day post
      discharge follow-up was carried out in 13 hospitals. Three hundred and forty-four
      patients who were diagnosed with STEMI or NSTEMI were recruited during the
      hospital stay. The pre-event QOL was measured using an interviewer-administered
      questionnaire which included the SF-36 QOL tool and medical details. Follow-up
      QOL was gathered using a questionnaire that was filled and posted back by
      participants. Of the recruited sample, 235 responded for the follow-up component.
      Analysis was conducted for associations between pre- and post-discharge QOL.
      Furthermore, comparisons were made between the STEMI and NSTEMI groups. Mann
      Whiney U test, Wilcoxon signed rank test and chi square test were used in the
      analysis. RESULTS: The post-event QOL was lower in seven out of eight domains
      than the pre-event QOL (p < 0.05). The NSTEMI group had more risk factors and a
      significantly lower pre-event QOL for seven domains (p < 0.05), when compared to
      the STEMI group. For seven domains, the post-discharge QOL was not significantly
      different (p > 0.05) between the STEMI and NSTEMI groups. Post-discharge general
      health QOL domain score was higher than the pre-MI score (p = 0.028) and was
      higher in the STEMI group compared to the NSTEMI group (p = 0.042). Regression
      analysis showed a significant beta coefficient between pre- and post-QOL for five
      domains in STEMI and for all domains in NSTEMI groups when adjusted for the
      disease severity. The R square values ranged from 12.3 to 62.3% for STEMI and 7.3
      to 64.8% for NSTEMI. CONCLUSIONS: Pre-event QOL is lower in the NSTEMI group
      compared to the STEMI group. Patients do not regain the previous QOL within one
      month post-discharge. Post-discharge QOL can be predicted by the pre-event QOL
      for most domains.

PMID- 28764726
TI  - How many holes is too many? A prototype tool for estimating mosquito entry risk
      into damaged bed nets.
AB  - BACKGROUND: Insecticide-treated bed nets (ITNs) have played an integral role in
      malaria reduction but how insecticide depletion and accumulating physical damage
      affect ITN performance is poorly understood. More accurate methods are needed to
      assess damage to bed nets so that they can be designed, deployed and replaced
      optimally. METHODS: Video recordings of female Anopheles gambiae in near approach
      (1-1/2 cm) to occupied untreated rectangular bed nets in a laboratory study were
      used to quantify the amount of mosquito activity (appearances over time) around
      different parts of the net, the per-appearance probability of a mosquito coming
      close to holes of different sizes (hole encounter) and the per-encounter
      probability of mosquitoes passing through holes of different sizes (hole
      passage). RESULTS: Appearance frequency on different parts of the net reflected
      previously reported patterns: the area of the net under greatest mosquito
      pressure was the roof, followed by the bottom 30 cm of the sides, followed by the
      30 cm area immediately above this, followed by the upper two-thirds of the sides.
      The ratio of activity in these areas was (respectively) 250:33:5:1. Per
      appearance probability of hole encounter on all parts of the net was strongly
      predicted by a factor combining hole perimeter and area. Per-encounter
      probability of hole passage, in turn, was strongly predicted by hole width. For a
      given width, there was a 20% greater risk of passage through holes on the roof
      than holes on the sides. DISCUSSION: Appearance, encounter and passage predictors
      correspond to various mosquito behaviours that have previously been described and
      are combined into a prototype mosquito entry risk tool that predicts mosquito
      entry rates for nets with various amounts of damage. Scenarios that use the entry
      risk tool to test the recommendations of the WHOPES proportionate hole index
      (pHI) suggest that the pHI hole size categories and failure to account for hole
      location likely sometimes lead to incorrect conclusions about net serviceability
      that could be avoided by using an entry risk tool of the form presented here
      instead. Practical methods of collecting hole position, shape and size
      information for bed net assessments using the tool in the field are discussed and
      include using image analysis and on-line geometric analysis tools.

PMID- 28764725
TI  - Distinct effects of EGFR inhibitors on epithelial- and mesenchymal-like
      esophageal squamous cell carcinoma cells.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) plays a pivotal role in the
      pathophysiology of esophageal squamous cell carcinoma (ESCC). However, the
      clinical effects of EGFR inhibitors on ESCC are controversial. This study sought
      to identify the factors determining the therapeutic efficacy of EGFR inhibitors
      in ESCC cells. METHODS: Immortalized-human esophageal epithelial cells (EPC2
      hTERT), transformed-human esophageal epithelial cells (T-Epi and T-Mes), and ESCC
      cells (TE-1, TE-5, TE-8, TE-11, TE-11R, and HCE4) were treated with the EGFR
      inhibitors erlotinib or cetuximab. Inhibitory effects on cell growth were
      assessed by cell counting or cell-cycle analysis. The expression levels of genes
      and proteins such as involucrin and cytokeratin13 (a squamous differentiation
      marker), E-cadherin, and vimentin were evaluated by real-time polymerase chain
      reaction or western blotting. To examine whether mesenchymal phenotype influenced
      the effects of EGFR inhibitors, we treated T-Epi cells with TGF-beta1 to
      establish a mesenchymal phenotype (mesenchymal T-Epi cells). We then compared the
      effects of EGFR inhibitors on parental T-Epi cells and mesenchymal T-Epi cells.
      TE-8 (mesenchymal-like ESCC cells)- or TE-11R (epithelial-like ESCC cells)
      derived xenograft tumors in mice were treated with cetuximab, and the antitumor
      effects of EGFR inhibitors were evaluated. RESULTS: Cells were classified as
      epithelial-like or mesenchymal-like phenotypes, determined by the expression
      levels of E-cadherin and vimentin. Both erlotinib and cetuximab reduced cell
      growth and the ratio of cells in cell-cycle S phase in epithelial-like but not
      mesenchymal-like cells. Additionally, EGFR inhibitors induced squamous cell
      differentiation (defined as increased expression of involucrin and cytokeratin13)
      in epithelial-like but not mesenchymal-like cells. We found that EGFR inhibitors
      did not suppress the phosphorylation of EGFR in mesenchymal-like cells, while
      EGFR dephosphorylation was observed after treatment with EGFR inhibitors in
      epithelial-like cells. Furthermore, mesenchymal T-Epi cells showed resistance to
      EGFR inhibitors by circumventing the dephosphorylation of EGFR signaling.
      Cetuximab consistently showed antitumor effects, and increased involucrin
      expression in TE-11R (epithelial-like)-derived xenograft tumors but not TE-8
      (mesenchymal-like)-derived xenograft tumors. CONCLUSIONS: The factor determining
      the therapeutic effects of EGFR inhibitors in ESCC cells is the phenotype
      representing the epithelial-like or mesenchymal-like cells. Mesenchymal-like ESCC
      cells are resistant to EGFR inhibitors because EGFR signaling is not blocked.
      EGFR inhibitors show antitumor effects on epithelial-like ESCC cells accompanied
      by promotion of squamous cell differentiation.

PMID- 28764727
TI  - EMQIT: a machine learning approach for energy based PWM matrix quality
      improvement.
AB  - BACKGROUND: Transcription factor binding affinities to DNA play a key role for
      the gene regulation. Learning the specificity of the mechanisms of binding TFs to
      DNA is important both to experimentalists and theoreticians. With the development
      of high-throughput methods such as, e.g., ChiP-seq the need to provide unbiased
      models of binding events has been made apparent. We present EMQIT a modification
      to the approach introduced by Alamanova et al. and later implemented as 3DTF
      server. We observed that tuning of Boltzmann factor weights, used for conversion
      of calculated energies to nucleotide probabilities, has a significant impact on
      the quality of the associated PWM matrix. RESULTS: Consequently, we proposed to
      use receiver operator characteristics curves and the 10-fold cross-validation to
      learn best weights using experimentally verified data from TRANSFAC database. We
      applied our method to data available for various TFs. We verified the efficiency
      of detecting TF binding sites by the 3DTF matrices improved with our technique
      using experimental data from the TRANSFAC database. The comparison showed a
      significant similarity and comparable performance between the improved and the
      experimental matrices (TRANSFAC). Improved 3DTF matrices achieved significantly
      higher AUC values than the original 3DTF matrices (at least by 0.1) and, at the
      same time, detected notably more experimentally verified TFBSs. CONCLUSIONS: The
      resulting new improved PWM matrices for analyzed factors show similarity to
      TRANSFAC matrices. Matrices had comparable predictive capabilities. Moreover,
      improved PWMs achieve better results than matrices downloaded from 3DTF server.
      Presented approach is general and applicable to any energy-based matrices. EMQIT
      is available online at http://biosolvers.polsl.pl:3838/emqit . REVIEWERS: This
      article was reviewed by Oliviero Carugo, Marek Kimmel and Istvan Simon.

PMID- 28764728
TI  - How do stakeholders from multiple hierarchical levels of a large provincial
      health system define engagement? A qualitative study.
AB  - BACKGROUND: Engaging stakeholders from varied organizational levels is essential
      to successful healthcare quality improvement. However, engagement has been hard
      to achieve and to measure across diverse stakeholders. Further, current
      implementation science models provide little clarity about what engagement means,
      despite its importance. The aim of this study was to understand how stakeholders
      of healthcare improvement initiatives defined engagement. METHODS: Participants
      (n = 86) in this qualitative thematic study were purposively sampled for
      individual interviews. Participants included leaders, core members, frontline
      clinicians, support personnel, and other stakeholders of Strategic Clinical
      Networks in Alberta Health Services, a Canadian provincial health system with
      over 108,000 employees. We used an iterative thematic approach to analyze
      participants' responses to the question, "How do you define engagement?" RESULTS:
      Regardless of their organizational role, participants defined engagement through
      three interrelated themes. First, engagement was active participation from
      willing and committed stakeholders, with levels that ranged from information
      sharing to full decision-making. Second, engagement centered on a shared decision
      making process about meaningful change for everyone "around the table," those who
      are most impacted. Third, engagement was two-way interactions that began early in
      the change process, where exchanges were respectful and all stakeholders felt
      heard and understood. CONCLUSIONS: This study highlights the commonalities of how
      stakeholders in a large healthcare system defined engagement-a shared
      understanding and terminology-to guide and improve stakeholder engagement.
      Overall, engagement was an active and committed decision-making about a
      meaningful problem through respectful interactions and dialog where everyone's
      voice is considered. Our results may be used in conjunction with current
      implementation models to provide clarity about what engagement means and how to
      engage various stakeholders.

PMID- 28764729
TI  - Does one size really fit all? The effectiveness of a non-diagnosis-specific
      integrated mental health care program in Germany in a prospective, parallel-group
      controlled multi-centre trial.
AB  - BACKGROUND: The Network for Mental Health (NWpG-IC) is an integrated mental
      health care program implemented in 2009 by cooperation between health insurance
      companies and community mental health providers in Germany. Meanwhile about
      10,000 patients have been enrolled. This is the first study evaluating the
      effectiveness of the program in comparison to standard mental health care in
      Germany. METHODS: In a parallel-group controlled trial over 18 months conducted
      in five regions across Germany, a total of 260 patients enrolled in NWpG-IC and
      251 patients in standard mental health care (TAU) were recruited between August
      2013 and November 2014. The NWpG-IC patients had access to special services such
      as community-based multi-professional teams, case management, crisis intervention
      and family-oriented psychoeducation in addition to standard mental health care.
      The primary outcome empowerment (EPAS) and the secondary outcomes quality of life
      (WHO-QoL-BREF), satisfaction with psychiatric treatment (CSQ-8), psychosocial and
      clinical impairment (HoNOS) and information about mental health service needs
      (CAN) were measured four times at 6-month intervals. Linear mixed-effect
      regression models were used to estimate the main effects and interaction effects
      of treatment, time and primary diagnosis. Due to the non-randomised group
      assignment, propensity score adjustment was used to control the selection bias.
      RESULTS: NWpG-IC and TAU groups did not differ with respect to most primary and
      secondary outcomes in our participating patients who showed a broad spectrum of
      psychiatric diagnoses and illness severities. However, a significant improvement
      in terms of patients' satisfaction with psychiatric care and their perception of
      treatment participation in favour of the NWpG-IC group was found. CONCLUSIONS:
      Providing integrated mental health care for unspecific mentally ill target groups
      increases treatment participation and service satisfaction but seems not suitable
      to enhance the overall outcomes of mental health care in Germany. The
      implementation of strategies for ameliorating the needs orientation of the NWpG
      IC should be considered. TRIAL REGISTRATION: German Clinical Trial Register
      DRKS00005111 , registered 26 July 2013.

PMID- 28764730
TI  - Objectively measured physical activity patterns, sedentary time and parent
      reported screen-time across the day in four-year-old Swedish children.
AB  - BACKGROUND: Physical activity (PA) improves health outcomes accumulating evidence
      suggests that sedentary time (ST), especially parent-reported screen-time, is
      associated with negative health outcomes in children. The aim of the present
      study is to describe levels and patterns of PA and ST across the day and week and
      activity pattern differences between the sexes, across all weekdays and time
      spent in and outside the preschool in four-year old children. METHODS: In total
      899 four-year old Swedish children who had both complete questionnaire data on
      screen-time behaviors and objective activity variables and at least 4 days,
      including one weekend day, with more than 10 h of GT3X+ Actigraph accelerometer
      wear time data were included in the study. Patterns of PA and ST across the day
      and week and differences between sexes, weekdays vs. weekend days and time in
      preschool vs. time spent outside preschool were assessed. RESULTS: Children
      engaged in 150 min (SD 73) and 102 min (SD 60) of screen-time on weekend days and
      weekdays, with 97% and 86% of children exceeding the 1 h guideline for screen
      time on weekend days and weekdays, respectively. Accelerometer data showed that
      boys are more active and less sedentary compared with girls and both sexes were
      more active and less sedentary on weekdays compared with weekend days, while
      parent-reported data showed that boys engage in more screen-time compared with
      girls. Children accumulated 24.8 min (SD. 19) MVPA during preschool time and 26.6
      min (SD. 16) outside preschool hours on weekdays, compared with 22.4 min (SD. 18)
      MVPA during preschool time and 25.3 min (SD. 22) outside preschool hours on
      weekend days. CONCLUSIONS: Four-year old Swedish children display different
      activity patterns across the day on weekdays compared to weekend days, with
      preschool hours during weekdays being the most active segments and preschool
      hours during weekend days being the least active segments of the day.

PMID- 28764731
TI  - Evaluation of the colorectal cancer screening Programme in the Basque Country
      (Spain) and its effectiveness based on the Miscan-colon model.
AB  - : The population-based Basque Colorectal Cancer (CRC) Screening Programme started
      in 2009 with a biennial immunochemical quantitative test (FIT) biennial and
      colonoscopy under sedation in positive cases. The population target of 586,700
      residents was from 50 to 69 years old and the total coverage was reached at the
      beginning of 2014. The aim of our study was to determine possible scenarios in
      terms of incidence, mortality and reduction of Life-years-Lost (L-y-L) in the
      medium and long term of CRC. METHODS: Invitations were sent out by the Programme
      from 2009 to 2014, with combined organizational strategies. Simulation was done
      by MISCAN-colon (Microsimulation Screening Analysis) over 30 years comparing the
      results of screening vs no-screening, taking the population-based Cancer Registry
      into account. Lifetime population and real data from the Programme were used from
      2008 to 2012. The model was run differentially for men and women. RESULTS:
      924,416 invitations were sent out from 2009 to 2014. The average participation
      rate was 68.4%, CRC detection rate was 3.4% and the Advanced Adenoma detection
      rate was 24.00/00, with differences observed in sex and age. Future scenarios
      showed a higher decrease of incidence (17.2% vs 14.7%), mortality (28.1% vs
      22.4%) and L-y-L (22.6% vs 18.4%) in men than women in 2030. CONCLUSIONS: The
      Basque Country CRC Programme results are aligned to its strategy and comparable
      to other programmes. MISCAN model was found to be a useful tool to predict the
      benefits of the programme in the future. The effectiveness of the Programme has
      not been formally established as case control studies are required to determine
      long term benefits from the screening strategy.

PMID- 28764732
TI  - In vitro and in vivo activity of R- and S- praziquantel enantiomers and the main
      human metabolite trans-4-hydroxy-praziquantel against Schistosoma haematobium.
AB  - BACKGROUND: Praziquantel (PZQ) is the mainstay of schistosomiasis control and has
      been successfully used for decades. However, its mechanism of action is not fully
      understood. While the majority of studies have been conducted on Schistosoma
      mansoni, it is not known which enantiomer, R- or S-praziquantel (R-/S-PZQ), is
      responsible for the activity on Schistosoma haematobium. METHODS: In vitro and in
      vivo studies were conducted to evaluate the activity of R- and S-PZQ, racemic PZQ
      and the main human metabolite, namely trans-4-OH-PZQ, on S. haematobium. IC50
      values on adult S. haematobium were determined in vitro. Dose-response
      relationship studies were performed in golden Syrian hamsters, harbouring a
      chronic S. haematobium infection. RESULTS: R-PZQ displayed the highest activity
      against adult worms in vitro, revealing an IC50 of 0.007 MUg/ml at 4 h and 0.01
      MUg/ml at 72 h. In contrast, S-PZQ was 501* less active (eudysmic ratio at 4 h),
      with an IC50 of 3.51 and 3.40 MUg/ml (4 and 72 h, respectively). Racemic PZQ and
      trans-4-OH-PZQ resulted in an IC50 of 0.03 MUg/ml and 1.47 MUg/ml both at 4 and
      72 h, respectively. In vivo, R-PZQ was the most potent drug with worm burden
      reductions (WBRs) of 98.5, 75.6 and 73.3% at 125.0, 62.5 and 31.0 mg/kg,
      respectively. A single oral dose of 250.0 mg/kg PZQ resulted in a WBR of 99.3%. S
      PZQ was highly active in vivo at 250.0 and 500.0 mg/kg with WBRs of 83.0 and
      94.1%, respectively. The lowest tested dose of S-PZQ, 125.0 mg/kg, showed
      moderate activity (WBR of 46.7%). The calculated ED50 for R- and S-PZQ were 24.7
      and 127.6 mg/kg, respectively, with a corresponding eudysmic ratio of 5.17.
      CONCLUSION: Our data support the theory of R-PZQ driving the antischistosomal
      activity. Interestingly, also S-PZQ proved to possess a significant activity
      towards S. haematobium, particularly in vivo.

PMID- 28764733
TI  - Associations of cause-specific mortality with area level deprivation and travel
      time to health care in France from 1990 to 2007, a multilevel analysis.
AB  - BACKGROUND: It is now widely accepted that social and physical environment
      participate in shaping health. While mortality is used to guide public health
      policies and is considered as a synthetic measure of population health, few
      studies deals with the contextual features potentially associated with mortality
      in a representative sample of an entire country. This paper investigates the
      possible role of area deprivation (FDep99) and travel time to health care on
      French cause-specific mortality in a proper multilevel setting. METHODS: The
      study population was a 1% sample representative of the French population aged
      from 30 to 79 years in 1990 and followed up until 2007. A frailty Cox model was
      used to measure individual, contextual effects and spatial variances for several
      causes of death. The chosen contextual scale was the Zone d'Emploi of 1994 (348
      units) which delimits the daily commute of people. The geographical accessibility
      to health care score was constructed with principal component analysis, using 40
      variables of hospital specialties and health practitioners' travel time. RESULTS:
      The outcomes highlight a positive and significant association between area
      deprivation and mortality for all causes (HR = 1.24), cancers, cerebrovascular
      diseases, ischemic heart diseases, and preventable and amenable diseases (HR from
      1.14 to 1.29). These contextual associations exhibit no substantial differences
      by sex except for premature ischemic heart diseases mortality which was much
      greater in women. Unexpectedly, mortality decreased as the time to reach health
      care resources increased. Only geographical disparities in cerebrovascular and
      ischemic heart diseases mortality were explained by compositional and contextual
      effects. DISCUSSION: The findings suggest the presence of confounding factors in
      the association between mortality and travel time to health care, possibly owing
      to population density and health-selected migration. Although the spatial scale
      considered to define the context of residence was relatively large, the
      associations with area deprivation were strong in comparison to the existing
      literature and significant for almost all the causes of deaths investigated.
      CONCLUSION: The broad spectrum of diseases associated with area deprivation and
      individual education support the idea of a need for a global health policy
      targeting both individual and territories to reduce social and socio-spatial
      inequalities.

PMID- 28764734
TI  - Development of a core outcome set for clinical trials in facial aging: study
      protocol for a systematic review of the literature and identification of a core
      outcome set using a Delphi survey.
AB  - BACKGROUND: Facial aging is a concern for many patients. Wrinkles, loss of
      volume, and discoloration are common physical manifestations of aging skin.
      Genetic heritage, prior ultraviolet light exposure, and Fitzpatrick skin type may
      be associated with the rate and type of facial aging. Although many clinical
      trials assess the correlates of skin aging, there is heterogeneity in the
      outcomes assessed, which limits the quality of evaluation and comparison of
      treatment modalities. To address the inconsistency in outcomes, in this project
      we will develop a core set of outcomes that are to be evaluated in all clinical
      trials relevant to facial aging. METHODS/DESIGN: A long list of measureable
      outcomes will be created from four sources: (1) systematic medical literature
      review, (2) patient interviews, (3) other published sources, and (4) stakeholder
      involvement. Two rounds of Delphi processes with homogeneous groups of physicians
      and patients will be performed to prioritize and condense the list. At a
      consensus meeting attended by physicians, patients, and stakeholders, outcomes
      will be further condensed on the basis of participant scores. By the end of the
      meeting, members will vote and decide on a final recommended set of core
      outcomes. Subsequent to this, specific measures will be selected or created to
      assess these outcomes. DISCUSSION: The aim of this study is to develop a core
      outcome set and relevant measures for clinical trials relevant to facial aging.
      We hope to improve the reliability and consistency of outcome reporting of skin
      aging, thereby enabling improved evaluation of treatment efficacy and patient
      satisfaction. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials
      (COMET) Initiative, accessible at http://www.comet
      initiative.org/studies/details/737 . Core Outcomes Set Initiative, (CSG-COUSIN)
      accessible at https://www.uniklinikum-dresden.de/de/das
      klinikum/universitaetscentren/zegv/cousin/meet-the-teams/project-groups/core
      outcome-set-for-the-appearance-of-facial-aging . Protocol version date is 28 July
      2016.

PMID- 28764735
TI  - Occurrence of cardiorespiratory diseases and impact on lifespan in Swedish Irish
      Wolfhounds: a retrospective questionnaire-based study.
AB  - BACKGROUND: According to Swedish animal insurance data, Irish Wolfhounds (IW) are
      29 times more likely to die from cardiac causes than the baseline breed. Dilated
      cardiomyopathy (DCM) has a high prevalence in the breed and the disease has been
      shown to be hereditary in IW. Few studies address respiratory diseases in IW, but
      reports suggest that the incidence of pneumonia is high. Respiratory diseases are
      reported as a common cause of death in the breed along with cardiac, neoplastic,
      musculoskeletal and gastrointestinal diseases. The aim of this study was to
      investigate mortality, morbidity and lifespan in Swedish IW through a
      questionnaire-based study. Focus was on DCM and pneumonia and potential
      association between these diseases. Questionnaires were sent to owners of
      purebred IW registered in the Swedish Kennel Club, born during 2006-2008. Owners
      were asked for information concerning occurrence of disease, results of clinical
      examinations, treatments, cause and date of death. RESULTS: Overall response rate
      was 38% (105 completed questionnaires). Median lifespan was 2720 days (7.5
      years). Males had shorter lifespan than females (median 2523 and 2836 days,
      respectively), P = 0.02. The most common causes of death were neoplastic disease
      (24%), cardiac disease (18%) and respiratory disease (16%). The percentage of
      dogs with pneumonia on at least one occasion during their lifetime was 37%, with
      a majority experiencing recurrent episodes (53%). The median lifespan was shorter
      for dogs affected by pneumonia on at least one occasion (2629 days), compared to
      dogs without history of pneumonia (2804 days) (P = 0.04), whereas the lifespan
      did not differ between dogs with or without a diagnosis of DCM. No sex
      predisposition was found regarding DCM or pneumonia. CONCLUSIONS: This study
      showed that DCM and pneumonia are common conditions in IW in Sweden, and that
      dogs affected by pneumonia have a shorter lifespan than those without history of
      pneumonia. Considering the results from this study and previous studies regarding
      these diagnoses in IW; cardiac and respiratory disease should be given further
      attention in the course of improving the general health of the breed.

PMID- 28764736
TI  - Quadriacanthus species (Monogenea: Dactylogyridae) from catfishes (Teleostei:
      Siluriformes) in eastern Africa: new species, new records and first insights into
      interspecific genetic relationships.
AB  - BACKGROUND: African catfishes of the families Bagridae and Clariidae are known to
      be parasitized with monogeneans of Quadriacanthus Paperna, 1961 (Dactylogyridae).
      The genus remains taxonomically challenging due to its speciose nature and
      relatively wide host range representing two fish orders, i.e. Siluriformes and
      Osteoglossiformes, in Africa and Asia. Here, we investigated diversity of
      Quadriacanthus spp. parasitizing Clarias gariepinus (Burchell), Heterobranchus
      bidorsalis Geoffroy Saint-Hilaire, and Bagrus docmak (Forsskal) collected in the
      Lake Turkana (Kenya) and Nile River Basin (Sudan). The interspecific
      relationships among Quadriacanthus spp. parasitizing catfishes inferred from
      ribosomal DNA sequences were investigated for the first time. METHODS: A combined
      morphological and molecular approach was used for description of the new species
      and for a critical review of the previously described Quadriacanthus spp., by
      means of phase contrast microscopic examination of sclerotized structures, and
      assessing the genetic divergence among the species found using rDNA sequences.
      RESULTS: Seven species (including four new) of Quadriacanthus were identified.
      These were as follows: Quadriacanthus aegypticus El-Naggar & Serag, 1986,
      Quadriacanthus clariadis Paperna, 1961, Quadriacanthus fornicatus n. sp.,
      Quadriacanthus pravus n. sp., and Quadriacanthus zuheiri n. sp. from Clarias
      gariepinus (Clariidae); Quadriacanthus mandibulatus n. sp. from Heterobranchus
      bidorsalis (Clariidae); and Quadriacanthus bagrae Paperna, 1979 from Bagrus
      docmak (Bagridae). For both 18S-ITS1 and 28S rDNA regions, Q. clariadis from a
      clariid fish was found to be most closely related to Q. bagrae from a bagrid
      host. Quadriacanthus mandibulatus n. sp. was observed to be the most distant
      species from the others. The separation of Q. mandibulatus n. sp. from the other
      species corresponds with the different morphology of its copulatory tube. The
      copulatory tube is terminally enlarged in Q. mandibulatus n. sp., while the tube
      in all other congeners studied is comparatively small and with an oblique
      tapering termination. CONCLUSIONS: This study contributes to a better
      understanding of African dactylogyrid diversity and provides the first molecular
      characterization of Quadriacanthus spp. The observed interspecific genetic
      relationships among Quadriacanthus spp. from clariids and Q. bagrae from a bagrid
      host suggest a possible host-switching event in the evolutionary history of the
      genus. Our records extend the currently known geographical range for
      Quadriacanthus spp. to Kenya and Sudan.

PMID- 28764737
TI  - The reproductive pattern and potential of free ranging female wild boars (Sus
      scrofa) in Sweden.
AB  - BACKGROUND: The number and spatial distribution of wild boars (Sus scrofa) has
      increased remarkably in Sweden as well as in other European countries. To
      understand the population dynamics of the wild boar, knowledge of its
      reproductive period, oestrus cycle and reproductive success is essential. The aim
      of this study was therefore to describe the seasonal reproductive pattern and
      reproductive potential of a wild boar population in Sweden. The study was based
      on findings from macroscopic examinations of the reproductive organs from 575
      hunter-harvested female wild boars (>30 kg body weight). Samples were collected
      between December 2011 and December 2015 in the southern and middle parts of
      Sweden. The age of the sampled animals was determined and dressed weight was
      noted. The stage of the reproductive cycle was defined according to ovarian
      structures and in relation to the appearance of/and findings in the uterus. The
      crown-rump length (CRL) of the embryos/foetuses was used to calculate the
      oestrus/mating month and month for the expected farrowing. RESULTS: The
      macroscopic examination revealed a seasonal variation of reproductive stages,
      although cyclic and pregnant females were found in all seasons. Moreover, the
      estimated oestrus/mating and farrowing months based on the CRL showed that mating
      and farrowing may occur 'off-season'. The average litter size (no. of embryos or
      foetuses) per pregnant female was 5.4. Sow weight and age had significant effect
      on both the reproductive potential (ovulation rate and litter size) and pregnancy
      rate, respectively. CONCLUSIONS: The reproductive potential in the studied wild
      boar population was high compared to studies from other countries and farrowing
      may occur 'off-season'. This suggests that the environmental conditions in
      Sweden, including supplemental feeding, are favourable for wild boar
      reproduction.

PMID- 28764738
TI  - Policy approaches to improve availability and affordability of medicines in
      Mexico - an example of a middle income country.
AB  - BACKGROUND: The World Health Organization recommends establishing and
      implementing a national pharmaceutical policy (NPP) to guarantee effective and
      equitable access to medicines. Mexico has implemented several policy approaches
      to regulate the pharmaceutical sector, but it has no formal NPP. This article
      describes the approach that the Mexican government has taken to improve
      availability and affordability of essential medicines. METHODS: Descriptive
      policy analysis of public pharmaceutical policy proposals and health action plans
      on the basis of publicly available data and health progress reports, with a focus
      on availability and affordability of medicines. RESULTS: The government has
      implemented pooled procurement, price negotiations, and an information platform
      in the public sector to improve affordability and availability. The government
      mainly reports on the savings that these strategies have generated in the public
      expenditure but their full impact on availability and affordability has not been
      assessed. CONCLUSIONS: To increase availability and affordability of medicines in
      the public sector, the Mexican government has resorted on isolated strategies. In
      addition to efficient procurement, price negotiations and price information,
      other policy components and pricing interventions are needed. All these
      strategies should be included in a comprehensive NPP.

PMID- 28764739
TI  - The substructure of three repetitive DNA regions of Schistosoma haematobium group
      species as a potential marker for species recognition and interbreeding
      detection.
AB  - BACKGROUND: Schistosoma haematobium is the causative agent of human urogenital
      schistosomiasis affecting ~112 million people in Africa and the Middle East. The
      parasite is transmitted by snails of the genus Bulinus, which also transmit other
      closely related human and animal schistosomes. The accurate discrimination of S.
      haematobium from species infecting animals will aid effective control and
      elimination programs. Previously we have shown the utility of different
      repetitive nuclear DNA sequences (DraI, sh73bp, and sh77bp) for the
      identification of S. haematobium-group species and inter-repeat sequences for
      discriminating S. haematobium from S. bovis. RESULTS: In this current study we
      clarify the structural arrangement and association between the three repetitive
      sequences (DraI, sh73bp, and sh77bp) in both S. haematobium and S. bovis, with a
      unique repeat linker being found in S. haematobium (Sh64bp repeat linker) and in
      S. bovis (Sb30bp repeat linker). Sequence data showed that the 3'-end of the
      repeat linker was connected to the DraI repetitive sequence array, and at the 5'
      end of the repeat linker sh73bp and sh77bp were arranged in an alternating
      manner. Species-specific oligonucleotides were designed targeting the species
      specific repeat linkers and used in a reverse line blot (RLB) hybridization assay
      enabling differentiation between S. haematobium and S. bovis. The assay was used
      to discriminate natural infections in wild caught Bulinus globosus. CONCLUSION:
      This research enabled the characterisation of species-specific DNA regions that
      enabled the design of species-specific oligonucleotides that can be used to
      rapidly differentiate between S. haematobium and S. bovis and also have the
      potential to aid the detection of natural hybridization between these two
      species.

PMID- 28764740
TI  - Variation of stemness markers expression in tumor nodules from synchronous multi
      focal hepatocellular carcinoma - an immunohistochemical study.
AB  - BACKGROUND: Advancing knowledge in molecular pathogenesis of hepatocellular
      carcinoma (HCC) opens up new horizons in the diagnostic, prognostic and
      therapeutic perspectives. Assessing the expression of molecular targets prior to
      definitive treatment is gaining importance in clinical practice. In this study,
      we investigated the variation in expression pattern of stemness markers in
      synchronous multi-focal HCC. METHODS: In the first cohort, 21 liver explants with
      multi-focal HCC were examined for expression of stemness markers EpCAM, Sox9 and
      CK19 by immunohistochemistry (IHC). Expression data of 50 tumor nodules were
      analyzed to determine the concordance of expression among nodules in the same
      livers. In the second cohort, 14 tumor nodules from 6 multi-focal HCC cases
      proven as intra-hepatic metastasis were examined for Soc9 immunoexpression.
      RESULTS: In the first cohort, thirty nodules from 16 cases expressed one or more
      markers, with Sox9 being most frequently expressed. Complete concordance of
      expression pattern for all 3 markers was observed in 6 cases. Discrepancy of
      staining degree was noted in 4 cases for EpCAM, 14 cases for Sox9, and 6 cases
      for CK19. A two-tier or three-tier difference in staining scores was noted in 5
      cases for Sox9 and one case for CK19. With Sox9, identical tumor morphology in
      terms of Edmondson grading and growth pattern did not infer the same degree of
      immunoexpression; and the largest tumor nodule was not representative of highest
      IHC score. In the second cohort of intra-hepatic metastasis, complete concordance
      of Sox9 expression level was observed in 5 out of 6 cases; while the remaining
      case showed a 1-tier difference of positive staining. CONCLUSIONS: Our findings
      suggested that clonality of tumor nodules is apparently an important factor to
      infer immunoexpression pattern. When there is limited information to discern
      multiple primaries versus intra-hepatic metastasis in multi-focal HCC, discordant
      degree of stemness markers expression among tumor nodules was commonly observed
      especially for markers with higher frequency of expression. Pathological features
      alone do not necessarily indicate the expression pattern of the synchronous
      nodule and in this scenario examination of each tumor nodule is justified.

PMID- 28764742
TI  - Pancreatic gangliocytic paraganglioma harboring lymph node metastasis: a case
      report and literature review.
AB  - BACKGROUND: Gangliocytic paraganglioma (GP) is a rare neuroendocrine neoplasm,
      which occurs mostly in the periampullary portion of the duodenum; the majority of
      the reported cases of duodenal GP has been of benign nature with a low incidence
      of regional lymph node metastasis. GP arising from the pancreas is extremely
      rare. To date, only three cases have been reported and its clinical
      characteristics are largely unknown. CASE PRESENTATION: A nodule located in the
      pancreatic head was incidentally detected in an asymptomatic 68-year-old woman.
      Computed tomography revealed 18-, 8-, and 12-mm masses in the pancreatic head,
      the pancreatic tail, and the left adrenal gland, respectively. Subsequent genetic
      examination revealed an absence of mutations in the MEN1 and VHL genes.
      Macroscopically, the tumor located in the pancreatic head was 22 mm in size and
      displayed an ill-circumscribed margin along with yellowish-white color.
      Microscopically, it was composed of three cell components: epithelioid cells,
      ganglion-like cells, and spindle cells, which led to the diagnosis of GP. The
      tumor was accompanied by a peripancreatic lymph node metastasis. The tumor in the
      pancreatic tail was histologically classified as a neuroendocrine tumor (NET) G1
      (grade 1, WHO 2010), whereas the tumor in the left adrenal gland was identified
      as an adrenocortical adenoma. The patient was disease-free at the 12-month follow
      up examination. CONCLUSIONS: Pancreatic GP is associated with a higher incidence
      of metastasis and larger tumor size than duodenal GPs, suggesting that the
      primary organ of GP is an important prognostic factor.

PMID- 28764743
TI  - One particular Anaplasma phagocytophilum ecotype infects cattle in the Camargue,
      France.
AB  - BACKGROUND: Anaplasma phagocytophilum is a zoonotic tick-borne pathogen
      responsible for granulocytic anaplasmosis, a mild to a severe febrile disease
      that affects man and several animal species, including cows and horses. In
      Europe, I. ricinus is the only proven vector for this pathogen, but studies
      suggest that other tick genera and species could be involved in its transmission.
      Our objective was to assess the presence and genetic diversity of A.
      phagocytophilum in domestic animals and different tick species from the Camargue
      region, located in the south of France. METHODS: A total of 140 ticks and blood
      samples from 998 cattle and 337 horses were collected in Camargue and tested for
      the presence of A. phagocytophilum DNA by msp2 quantitative real-time PCR.
      Molecular typing with four markers was performed on positive samples. RESULTS:
      Anaplasma phagocytophilum DNA was detected in 6/993 (0.6%) cows, 1/20 (5%)
      Haemaphysalis punctata, 1/57 (1.75%) Rhipicephalus pusillus, and was absent in
      horses (0%). All cattle A. phagocytophilum presented a profile identical to an A.
      phagocytophilum variant previously detected in Dermacentor marginatus, Hyalomma
      marginatum, and Rhipicephalus spp. in Camargue. CONCLUSIONS: Our results
      demonstrate that one particular A. phagocytophilum variant infects cattle in
      Camargue, where I. ricinus is supposed to be rare or even absent. Dermacentor
      marginatus, Rhipicephalus spp. and Hyalomma spp., and possibly other tick species
      could be involved in the transmission of this variant in this region.

PMID- 28764744
TI  - A case study of Desmozoon lepeophtherii infection in farmed Atlantic salmon
      associated with gill disease, peritonitis, intestinal infection, stunted growth,
      and increased mortality.
AB  - BACKGROUND: In September 2008, a disease outbreak characterized by acute, severe
      gill pathology and peritonitis, involving the gastrointestinal tract, was
      observed in an Atlantic salmon (Salmo salar L.) farm in north-western Norway.
      During subsequent sampling in November 2008 and January 2009, chronic
      proliferative gill inflammation and peritonitis was observed. Cumulative
      mortalities of 5.6-12.8% and severe growth retardation were observed. Routine
      diagnostic analysis revealed no diseases known to salmon at the time, but
      microsporidian infection of tissues was observed. METHODS: To characterize the
      disease outbreak, a combination of histopathology, in situ hybridization (ISH),
      chitin, calcofluor-white (CFW) staining, and real-time PCR were used to describe
      the disease progression with visualization of the D. lepeophtherii stages in
      situ. RESULTS: The presence of the microsporidian Desmozoon lepeophtherii was
      confirmed with real-time PCR, DNA sequencing and ISH, and the parasite was
      detected in association with acute lesions in the gills and peritoneum. ISH using
      a probe specific to small subunit 16S rRNA gene provided an effective tool for
      demonstrating the distribution of D. lepeophtherii in the tissue. Infection in
      the peritoneum seemed localized in and around pre-existing vaccine granulomas,
      and in the gastrointestinal walls. In the heart, kidney and spleen, the infection
      was most often associated with mononuclear leucocytes and macrophages, including
      melanomacrophages. Desmozoon lepeophtherii exospores were found in the nuclei of
      the gastrointestinal epithelium for the first time, suggesting a role of the
      gastrointestinal tract in the spread of spores to the environment. CONCLUSIONS:
      This study describes the progression of D. lepeophtherii disease outbreak in an
      Atlantic salmon farm without any other known diseases present. Using different
      methods to examine the disease outbreak, new insight into the pathology of D.
      lepeophtherii was obtained. The parasite was localized in situ in association
      with severe tissue damage and inflammation in the gills, peritoneal cavity and in
      the gastrointestinal (GI) tract that links the parasite directly to the observed
      pathology.

PMID- 28764741
TI  - The role of melatonin in the onset and progression of type 3 diabetes.
AB  - Alzheimer's disease (AD) is defined by the excessive accumulation of toxic
      peptides, such as beta amyloid (Abeta) plaques and intracellular neurofibrillary
      tangles (NFT). The risk factors associated with AD include genetic mutations,
      aging, insulin resistance, and oxidative stress. To date, several studies that
      have demonstrated an association between AD and diabetes have revealed that the
      common risk factors include insulin resistance, sleep disturbances, blood brain
      barrier (BBB) disruption, and altered glucose homeostasis. Many researchers have
      discovered that there are mechanisms common to both diabetes and AD. AD that
      results from insulin resistance in the brain is termed "type 3 diabetes".
      Melatonin synthesized by the pineal gland is known to contribute to circadian
      rhythms, insulin resistance, protection of the BBB, and cell survival mechanisms.
      Here, we review the relationship between melatonin and type 3 diabetes, and
      suggest that melatonin might regulate the risk factors for type 3 diabetes. We
      suggest that melatonin is crucial for attenuating the onset of type 3 diabetes by
      intervening in Abeta accumulation, insulin resistance, glucose metabolism, and
      BBB permeability.

PMID- 28764745
TI  - Magnitude and associated factors of anemia among pregnant women in Dera District:
      a cross-sectional study in northwest Ethiopia.
AB  - BACKGROUND: Anemia is associated with adverse health and socio-economic
      consequences among pregnant women. Particularly, severe anemia increases the risk
      of maternal mortality by 20%. However, literatures are scarce in the northwest
      Ethiopia. Therefore, this study aimed to determine the magnitude and associated
      factors of anemia among pregnant women attending antenatal care in Dera District,
      South Gondar Zone, northwest Ethiopia. METHODS: A facility-based cross-sectional
      study was conducted in Dera District health centers from June 27 to September 2,
      2015. Capillary blood samples were taken from 348 pregnant women. The raw
      measured values of hemoglobin were obtained using the portable Hb301 instrument
      and adjusted for altitude. Besides, nutritional status of the women was assessed
      by the mid upper arm circumference (MUAC) taken on non-dominant upper limb,
      mostly of the left hand. Socio-demographic factors, obstetric history,
      environmental related factors and dietary intake were collected by interviewing
      the pregnant women. A multivariate logistic regression analysis was employed to
      identify factors associated with anemia. Adjusted odds ratio (AOR) with
      corresponding 95% confidence interval (CI) was computed to show the strength of
      association. In multivariable analysis, a P value of <0.05 was used to declare
      statistical significance. RESULTS: The overall prevalence of anemia among
      pregnant women was 30.5% [95% CI 21.0, 40.0]. The result of multivariable
      analysis revealed that the likelihood of anemia was higher among pregnant women
      living in rural areas [AOR = 3.03, 95% CI 1.17, 7.82], had no latrine [AOR =
      4.75, 95% CI 1.15, 16.60], low monthly income: <Eth. Birr 1200 (US dollar 52.22)
      [AOR = 2.56, 95% CI 1.17, 5.60], five or above parity [AOR = 4.17; 95% CI 1.62,
      10.69], MUAC < 23 cm [AOR = 4.97; 95% CI 2.61, 9.43] and did not prenatal take
      iron supplementation [AOR = 5.63; 95% 2.21, 14.32]. CONCLUSION: So far in the
      district, the magnitude of anemia existed as a moderate public health concern.
      Thus, improved socio-economic status, latrine and maternal iron supplementation
      coverage are essential to mitigate the high burden of anemia. In addition,
      nutritional counseling and education on the consumption of extra meals and iron
      rich foods should be intensified.

PMID- 28764746
TI  - Percutaneous endoscopic lumbar discectomy: minimally invasive technique for
      multiple episodes of lumbar disc herniation.
AB  - BACKGROUNDS: Although open lumbar discectomy is a gold standard surgical
      technique for lumbar disc herniation (LDH), surgery-induced tissue injury may
      actually become a source of postsurgical pain. Percutaneous endoscopic lumbar
      discectomy (PELD) is introduced as a minimal invasive spinal technique for LDH.
      The PELD has gained popularity and shown successful results. The authors report
      the clinical usefulness of the PELD technique in two patients with the serial
      multilevel LDHs. CASE PRESENTATIONS: A 32-year-old man suffered from radicular
      pain at the L5 dermatome due to the down migrated soft LDH at the L4-5 level. The
      PELD was performed to remove the ruptured fragments, yielding a complete
      decompression of the L5 nerve root. Four years later, he visited the clinic
      because of right leg radiating pain along the S1 dermatome. An MRI scan revealed
      the LDH at the L5-S1 level. The PELD with foraminoplasty was also performed
      successfully at the L5-S1 level. Two months after the second PELD, he visited the
      clinic again because of severe pain along the left L4 dermatome; consequently,
      the PELD was also performed at the L3-4 level without any complications. A 34
      year-old man presented with radiating pain in the back and both legs at the L5
      dermatome. The MR images show a disc extrusion at the L4-5. The patient underwent
      the PELD at the L4-5 via the left approach. After the PELD, the back and leg pain
      both improved. One year later, the patient suffered from severe pain in the back
      and the left anterior thigh. The MR images show a left paramedian LDH at the L2
      3. After the PELD was performed at the L2-3, the pain was relieved. The final MR
      images show no signs of any aggravated degeneration of the intervertebral discs
      or the facet joints at all of the treated levels. CONCLUSION: When multiple
      episodes of LDH occur in a patient's life span, PELD could be considered as an
      alternative good technique to treat LDH in each step by preserving normal
      anatomic structures.

PMID- 28764747
TI  - Dengue-specific serotype related to clinical severity during the 2012/2013
      epidemic in centre of Brazil.
AB  - : Please see Additional file 1 for translations of the abstract into the five
      official working languages of the United Nations. BACKGROUND: Currently, in
      Brazil, there is a co-circulation of the four dengue (DENV-1 to DENV-4)
      serotypes. This study aimed to assess whether different serotypes and antibody
      response patterns were associated with the severity of the disease during a
      dengue outbreak, which occurred in 2012/2013 in centre of Brazil. METHODS: We
      conducted a prospective study with 452 patients with laboratory confirmed dengue
      in central Brazil, from January 2012 to July 2013. The clinical outcome was the
      severity of cases: dengue, dengue with warning signs, and severe dengue. The
      patients were evaluated at three different moments. Blood sampling for laboratory
      testing and confirmatory tests for dengue infection were performed. We performed
      a multinomial analysis considering the three categories of the dependent
      variable, as outlined above. The odds ratios (ORs) were calculated. A multinomial
      logistic regression model was applied for variables with a P-value <0.20.
      Statistical analysis was performed with STATA 12.0 software. RESULTS: Four
      hundred fifty-two patients (452/632, 71.5%) were diagnosed with dengue. The
      dengue virus (DENV) serotypes were identified in 243 cases. DENV-4 was detected
      in 135 patients (55.6%), DENV-1 in 91 (37.4%), DENV-3 in 13 (5.3%), and DENV-2 in
      4 (1.6%). Patients with the DENV-1 serotype were more prone to present with
      several clinical and laboratory features as compared with DENV-4 patients,
      including spontaneous bleeding (P = 0.03), intense abdominal pain (P = 0.004),
      neurological symptoms (P = 0.09), and thrombocytopenia (P = 0.01). Secondary
      infection was more predominant among DENV-4 cases (80.0%) compared with DENV-1
      cases (62.3%) (P = 0.03). The univariate analysis showed that females (OR = 2.12;
      95% CI: 1.44-3.13; P < 0.01) had a higher risk of having dengue with warning
      signs. The multinomial analysis showed that severe dengue cases with secondary
      infection had an adjusted OR of 2.80 (95% CI: 0.78-10.00; P = 0.113) as compared
      with dengue fever with primary infection when adjusted for age and sex.
      CONCLUSION: The current data show that 5.8% of patients recruited for treatment
      in healthcare centres and hospitals during the study period had severe dengue.
      DENV-4 was the predominant serotype, followed by DENV-1, in a large outbreak of
      dengue in central Brazil. Our findings contribute to the understanding of
      clinical differences and immune status related to the serotypes DENV-1 and DENV-4
      in central of Brazil.

PMID- 28764749
TI  - Evaluation of antimycobacterial, leishmanicidal and antibacterial activity of
      three medicinal orchids of Arunachal Pradesh, India.
AB  - BACKGROUND: The ethnic population of Arunachal Pradesh uses a number of orchids
      as such, or in decoction for various ailments. Three untapped orchids namely,
      Rhynchostylis retusa, Tropidia curculioides and Satyrium nepalense, traditionally
      used in tuberculosis, asthma and cold stage of malaria in folk medicine, were
      selected for the present study. METHODS: Dried material of each plant was divided
      into three parts. Solvent extraction and fractionation afforded altogether 30
      extracts and fractions, which were evaluated against Mycobacterium tuberculosis
      (H37Rv and MDR strain) for antimycobacterial activity; promastigotes and
      amastigotes of Leishmania donovani for leishmanicidal activity and two gram
      positive and three gram negative clinical isolates for antibacterial activity.
      RESULTS: The most significant antimycobacterial activity was observed with n
      hexane fraction of the flower of Satyrium nepalense with MIC of 15.7 MUg/mL. The
      most promising leishmanicidal activity was observed with diethyl ether fraction
      of the roots of Rhynchostylis retusa with IC50 values of 56.04 and 18.4 MUg/mL
      against promastigotes and intracellular amastigotes respectively. Evaluation of
      antibacterial activity identified S. nepalense flower n-hexane and R. retusa
      roots diethyl ether as potential fractions with MIC values of <=100 MUg/mL
      against selected clinical isolates. CONCLUSIONS: This is the first report of the
      plants possessing antimycobacterial and leishmanicidal activity. The
      investigation resulted in identification of S. nepalense as the most promising
      plant, which possessed all three activities in significant proportion. This
      laboratory outcome could be translated to marketable pharmaceutical products and
      also to produce maximum benefits to the local of nearby area. Antimycobacterial
      and leishmanicidal activity of medicinal orchids.

PMID- 28764748
TI  - A phase I trial of ganetespib in combination with paclitaxel and trastuzumab in
      patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic
      breast cancer.
AB  - BACKGROUND: Targeted therapies in HER2-positive metastatic breast cancer
      significantly improve outcomes but efficacy is limited by therapeutic resistance.
      HER2 is an acutely sensitive Heat Shock Protein 90 (HSP90) client and HSP90
      inhibition can overcome trastuzumab resistance. Preclinical data suggest that
      HSP90 inhibition is synergistic with taxanes with the potential for significant
      clinical activity. We therefore tested ganetespib, a HSP90 inhibitor, in
      combination with paclitaxel and trastuzumab in patients with trastuzumab
      refractory HER2-positive metastatic breast cancer. METHODS: In this phase I dose
      escalation study, patients with trastuzumab-resistant HER2-positive metastatic
      breast cancer received weekly trastuzumab (2 mg/kg) and paclitaxel (80 mg/m2) on
      days 1, 8, 15, and 22 of a 28-day cycle with escalating doses of ganetespib (100
      mg/m2, 150 mg/m2, and a third cohort of 125 mg/m2 if needed) on days 1, 8, and
      15. Therapy was continued until disease progression or toxicity. The primary
      objective was to establish the safety and maximum tolerated dose and/or
      recommended phase II dose (RP2D) of this therapy. The secondary objectives
      included evaluation of the effects of ganetespib on the pharmacokinetics of
      paclitaxel, and to make a preliminary assessment of the efficacy of the
      combination therapy. RESULTS: Dose escalation was completed for the two main
      cohorts without any observed dose-limiting toxicities. Nine patients received
      treatment. The median prior lines of anti-HER2 therapy numbered three (range 2
      4), including prior pertuzumab in 9/9 patients and ado-trastuzumab emtansine (T
      DM1) in 8/9 patients. The most common grade 1/2 adverse events (AEs) were
      diarrhea, fatigue, anemia, and rash. There were no grade 4 AEs related to
      ganetespib. The overall response rate was 22% (2/9 patients had partial response)
      and stable disease was seen in 56% (5/9 patients). The clinical benefit rate was
      44% (4/9 patients). The median progression-free survival was 20 weeks (range 8
      55). CONCLUSION: The RP2D of ganetespib is 150 mg/m2 in combination with weekly
      paclitaxel plus trastuzumab. The combination was safe and well tolerated. Despite
      prior taxanes, pertuzumab, and T-DM1, clinical activity of this triplet regimen
      in this heavily pretreated cohort is promising and warrants further study in HER2
      positive metastatic breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT02060253 . Registered 30 January 2014.

PMID- 28764750
TI  - Risk of head and traumatic brain injuries associated with antidepressant use
      among community-dwelling persons with Alzheimer's disease: a nationwide matched
      cohort study.
AB  - BACKGROUND: Antidepressant use has been associated with an increased risk of
      falling, but no studies have been conducted on whether antidepressant use is
      associated with an increased risk of head injuries which often result from
      falling among older persons. The objective of this study was to investigate the
      risk of head and brain injuries associated with antidepressant use among
      community-dwelling persons with Alzheimer's disease. METHODS: A matched cohort
      study was conducted by comparing new antidepressant users (n = 10,910) with two
      matched nonusers (n = 21,820) in the MEDALZ study cohort. The MEDALZ cohort
      includes all community-dwelling persons newly diagnosed with Alzheimer's disease
      between 2005 and 2011 in Finland. Incident antidepressant users were identified
      based on register-based dispensing data from the Prescription register with a 1
      year washout period for antidepressant use. Nonusers were matched with users
      based on age, gender, and time since Alzheimer's disease diagnosis. The outcome
      events were defined as any head injuries and traumatic brain injuries based on
      diagnoses in Hospital Discharge and Causes of Death registers. Propensity score
      adjusted Cox proportional hazard models were utilized. Sensitivity analyses with
      case-crossover design were conducted. All registers are linkable with unique
      personal identification numbers assigned for each resident. RESULTS:
      Antidepressant use was associated with an increased risk of head injuries (age
      adjusted event rate per 100 person-years 2.98 (95% confidence interval (CI) 2.49
      3.06) during use and 2.43 (95% CI 2.06-2.35) during nonuse, adjusted hazard ratio
      (HR) 1.35, 95% CI 1.20-1.52) and traumatic brain injuries (age-adjusted event
      rate per 100 person-years 1.33 (95% CI 1.13-1.53) during use and 1.10 (95% CI
      1.00-1.20) during nonuse, adjusted HR 1.26, 95% CI 1.06-1.50). The risk was
      highest during the first 30 days of use (HR 1.71, 95% CI 1.10-2.66 for head
      injuries; HR 2.06, 95% CI 1.12-3.82 for traumatic brain injuries) and remained at
      an elevated level for head injuries for over 2 years of use. In case-crossover
      analyses, antidepressant use was consistently associated with a higher risk of
      head injuries. CONCLUSIONS: Antidepressant use was associated with an increased
      risk of the most severe outcomes, head and brain injuries, in persons with
      Alzheimer's disease. Antidepressant use should be carefully considered and the
      association confirmed in future studies.

PMID- 28764751
TI  - The in vitro effects of interferon-gamma, alone or in combination with
      amphotericin B, tested against the pathogenic fungi Candida albicans and
      Aspergillus fumigatus.
AB  - OBJECTIVE: Recent studies into the antifungal activity of NK-cells against the
      Aspergillus fumigatus have presented differing accounts on their mode of
      antifungal activity. One of these mechanisms proposed that NK-cells may kill the
      fungus via the direct effects of exposure to Interferon gamma (IFN-gamma).
      RESULTS: In this study we investigated the direct antifungal effects of
      recombinant human IFN-gamma against a range of pathogenic fungi by measuring
      cellular damage using an XTT-based assay and cell viability through plate counts.
      It was found that 32 pg/ml of IFN-gamma exhibited a significant but small
      antifungal effect on A. fumigatus (p = 0.02), Aspergillus flavus (p = 0.04) and
      Saccharomyces cerevisiae (p = 0.03), inhibiting growth by 6, 11 and 17%
      respectively. No significant inhibitory effects were observed in Candida species
      (p > 0.05 for all species tested) or Cryptococus neoformans (p = 0.98). Short
      term exposure (3 h) to a combination of amphotericin B (1 ug/ml) and IFN-gamma
      (32 pg/ml) increased the effectiveness of amphotericin B against A. fumigatus and
      S. cerevisiae but not Candida albicans. These data suggest that IFN-gamma does
      not possess strong antifungal activity but can enhance the effect of amphotericin
      B under some testing conditions against Aspergillus species.

PMID- 28764752
TI  - Facilitated interprofessional implementation of a physical rehabilitation
      guideline for stroke in inpatient settings: process evaluation of a cluster
      randomized trial.
AB  - BACKGROUND: The Stroke Canada Optimization of Rehabilitation by Evidence
      Implementation Trial (SCORE-IT) showed that a facilitated knowledge translation
      (KT) approach to implementing a stroke rehabilitation guideline was more likely
      than passive strategies to improve functional walking capacity, but not gross
      manual dexterity, among patients in rehabilitation hospitals. This paper presents
      the results of a planned process evaluation designed to assess whether the type
      and number of recommended treatments implemented by stroke teams in each group
      would help to explain the results related to patient outcomes. METHODS: As part
      of a cluster randomized trial, 20 rehabilitation units were stratified by
      language and allocated to a facilitated or passive KT intervention group. Sites
      in the facilitated group received the guideline with treatment protocols and
      funding for a part-time nurse and therapist facilitator who attended a 2-day
      training workshop and promoted guideline implementation for 16 months. Sites in
      the passive group received the guideline excluding treatment protocols. As part
      of a process evaluation, nurses, and occupational and physical therapists,
      blinded to study hypotheses, were asked to record their implementation of 18
      recommended treatments targeting motor function, postural control and mobility
      using individualized patient checklists after treatment sessions for 2 weeks pre-
      and post-intervention. The percentage of patients receiving each treatment pre-
      and post-intervention and between groups was compared after adjusting for
      clustering and covariates in a random-effects logistic regression analysis.
      RESULTS: Data on treatment implementation from nine and eight sites in the
      facilitated and passive KT group, respectively, were available for analysis. The
      facilitated KT intervention was associated with improved implementation of sit-to
      stand (p = 0.028) and walking (p = 0.043) training while the passive KT
      intervention was associated with improved implementation of standing balance
      training (p = 0.037), after adjusting for clustering at patient and provider
      levels and covariates. CONCLUSIONS: Despite multiple strategies and resources,
      the facilitated KT intervention was unsuccessful in improving integration of 18
      treatments concurrently. The facilitated approach may not have adequately
      addressed barriers to integrating numerous treatments simultaneously and complex
      treatments that were unfamiliar to providers. TRIAL REGISTRATION: Unique
      identifier- NCT00359593.

PMID- 28764753
TI  - Supporting prescribing in older people with multimorbidity and significant
      polypharmacy in primary care (SPPiRE): a cluster randomised controlled trial
      protocol and pilot.
AB  - BACKGROUND: Multimorbidity, defined as the presence of at least two chronic
      conditions, becomes increasingly common in older people and is associated with
      poorer health outcomes and significant polypharmacy. The National Institute for
      Clinical Excellence (NICE) recently published a multimorbidity guideline that
      advises providing an individualised medication review for all people prescribed
      15 or more repeat medicines. This study incorporates this guideline and aims to
      assess the effectiveness of a complex intervention designed to support general
      practitioners (GPs) to reduce potentially inappropriate prescribing and consider
      deprescribing in older people with multimorbidity and significant polypharmacy in
      Irish primary care. METHODS: This study is a cluster randomised controlled trial,
      involving 30 general practices and 450 patients throughout Ireland. Practices
      will be eligible to participate if they have at least 300 patients aged 65 years
      and over on their patient panel and if they use either one of the two predominant
      practice management software systems in use in Ireland. Using a software patient
      finder tool, practices will identify and recruit patients aged 65 years and over,
      who are prescribed at least 15 repeat medicines. Once baseline data collection is
      complete, practices will be randomised using minimisation by an independent third
      party to either intervention or control. Given the nature of the intervention, it
      is not possible to blind participants or study personnel. GPs in intervention
      practices will receive login details to a website where they will access training
      videos and a template for conducting an individualised structured medication
      review, which they will undertake with each of their included patients. Control
      practices will deliver usual care over the 6-month study period. Primary outcome
      measures pertain to the individual patient level and are the proportion of
      patients with any PIP and the number of repeat medicines. DISCUSSION: Disease
      specific approaches in multimorbidity may be inappropriate and result in
      fragmented and poorly co-ordinated care. This pragmatic study is evaluating a
      complex intervention that is relevant across multiple conditions and addresses
      potential concerns around medicines safety in this vulnerable group of patients.
      The potential for system-wide implementation will be explored with a parallel
      mixed methods process evaluation. TRIAL REGISTRATION: ISRCTN: 12752680 ,
      Registered 20 October 2016.

PMID- 28764754
TI  - National policies for the promotion of physical activity and healthy nutrition in
      the workplace context: a behaviour change wheel guided content analysis of policy
      papers in Finland.
AB  - BACKGROUND: Health policy papers disseminate recommendations and guidelines for
      the development and implementation of health promotion interventions. Such
      documents have rarely been investigated with regard to their assumed mechanisms
      of action for changing behaviour. The Theoretical Domains Framework (TDF) and
      Behaviour Change Techniques (BCT) Taxonomy have been used to code behaviour
      change intervention descriptions, but to our knowledge such "retrofitting" of
      policy papers has not previously been reported. This study aims first to identify
      targets, mediators, and change strategies for physical activity (PA) and
      nutrition behaviour change in Finnish policy papers on workplace health
      promotion, and second to assess the suitability of the Behaviour Change Wheel
      (BCW) approach for this purpose. METHOD: We searched all national-level health
      policy papers effectual in Finland in August 2016 focusing on the promotion of PA
      and/or healthy nutrition in the workplace context (n = 6). Policy recommendations
      targeting employees' nutrition and PA including sedentary behaviour (SB) were
      coded using BCW, TDF, and BCT Taxonomy. RESULTS: A total of 125 recommendations
      were coded in the six policy papers, and in two additional documents referenced
      by them. Psychological capability, physical opportunity, and social opportunity
      were frequently identified (22%, 31%, and 24%, respectively), whereas physical
      capability was almost completely absent (1%). Three TDF domains (knowledge,
      skills, and social influence) were observed in all papers. Multiple intervention
      functions and BCTs were identified in all papers but several recommendations were
      too vague to be coded reliably. Influencing individuals (46%) and changing the
      physical environment (44%) were recommended more frequently than influencing the
      social environment (10%). CONCLUSIONS: The BCW approach appeared to be useful for
      analysing the content of health policy papers. Paying more attention to
      underlying assumptions regarding behavioural change processes may help to
      identify neglected aspects in current policy, and to develop interventions based
      on recommendations, thus helping to increase the impact of policy papers.

PMID- 28764755
TI  - 'The university should promote health, but not enforce it': opinions and
      attitudes about the regulation of sugar-sweetened beverages in a university
      setting.
AB  - BACKGROUND: The study aimed to determine the opinions and attitudes of a
      university population regarding the regulation of sugar-sweetened beverages in a
      university setting, primarily looking at differences in opinion between younger
      adults (under 30 years of age) and older adults (30 years of age or older).
      METHODS: An online survey was conducted at an Australian university in April-May
      2016 using a convenience sample of students and staff between the ages of 16 and
      84 years. The survey included questions about consumption of sugar-sweetened
      beverages and level of agreement and support of proposed sugar-sweetened beverage
      interventions. Quantitative response data and qualitative open-ended response
      data were analysed. RESULTS: Nine hundred thirteen responses from students and
      staff were analysed. In this population, consumption of sugar-sweetened beverages
      was low and awareness of the health risks of sugar-sweetened beverages was high.
      Overall, the surveyed population indicated more support for interventions that
      require higher levels of personal responsibility. The population did support some
      environment-centred, population-based interventions, such as increasing access to
      drinking water and reducing the price of healthier beverage alternatives. However
      there was less support for more restrictive interventions such as removing sugar
      sweetened beverages from sale. Young adults tended to be less supportive of most
      interventions than older adults. CONCLUSIONS: These findings indicate there is
      some support for environment-centred, population-based approaches to reduce the
      availability and appeal of sugar-sweetened beverages in an adult environment such
      as a university setting. However these results suggest that public health may
      need to focus less on educating populations about the harms associated with sugar
      sweetened beverages. Instead, there should be greater emphasis on explaining to
      populations and communities why environment-centred approaches relating to the
      sale and promotion of sugar-sweetened beverages should be prioritised over
      interventions that simply target personal responsibility and individual
      behaviours.

PMID- 28764756
TI  - A tailored within-community specimen collection strategy increased uptake of
      cervical cancer screening in a cross-sectional study in Ghana.
AB  - BACKGROUND: The implementation of cervical cancer screening strategies has
      reported different rates of success in different countries due to population
      specific factors that limit women's participation. We report observations and the
      development of a community-based specimen collection strategy which resulted from
      interactions with women in the study communities, following an initial low
      response to a hospital based cervical cancer screening strategy. METHOD: Women
      were recruited by a house survey and invited to report at a hospital either
      within a week or after a week for self and health-personnel specimen collections.
      However, due to the very low response and subsequent interactions with the women
      of the communities, another strategy was developed that required recruited women
      report at a central location within their respective communities for specimen
      collections at times that did not interfere with their daily routines. RESULTS:
      For specimen collection, of the 156 participants who opted to report after a week
      at the hospital, 60 (38.5%) reported. Of the 118 participants who opted to report
      within 1 week at the hospital, 55 (46.6%) reported. Of the 103 participants were
      invited to report at a specified location within the community, 98 (95.1%)
      reported. An overall response rate of 60.4% was attained. Almost 89.7% (226 of
      253) of the women performed both self and health personnel sample collection.
      CONCLUSION: The community-based strategy with self-specimen collection and HPV
      testing holds great potential for increasing women's participation in cervical
      cancer screening in Ghana as compared to the hospital based strategy.

PMID- 28764757
TI  - How accurate is the 'Surprise Question' at identifying patients at the end of
      life? A systematic review and meta-analysis.
AB  - BACKGROUND: Clinicians are inaccurate at predicting survival. The 'Surprise
      Question' (SQ) is a screening tool that aims to identify people nearing the end
      of life. Potentially, its routine use could help identify patients who might
      benefit from palliative care services. The objective was to assess the accuracy
      of the SQ by time scale, clinician, and speciality. METHODS: Searches were
      completed on Medline, Embase, CINAHL, AMED, Science Citation Index, Cochrane
      Database of Systematic Reviews, Cochrane Central Register of Controlled Trials,
      Open Grey literature (all from inception to November 2016). Studies were included
      if they reported the SQ and were written in English. Quality was assessed using
      the Newcastle-Ottawa Scale. RESULTS: A total of 26 papers were included in the
      review, of which 22 reported a complete data set. There were 25,718 predictions
      of survival made in response to the SQ. The c-statistic of the SQ ranged from
      0.512 to 0.822. In the meta-analysis, the pooled accuracy level was 74.8% (95% CI
      68.6-80.5). There was a negligible difference in timescale of the SQ. Doctors
      appeared to be more accurate than nurses at recognising people in the last year
      of life (c-statistic = 0.735 vs. 0.688), and the SQ seemed more accurate in an
      oncology setting 76.1% (95% CI 69.7-86.3). CONCLUSIONS: There was a wide degree
      of accuracy, from poor to reasonable, reported across studies using the SQ.
      Further work investigating how the SQ could be used alongside other prognostic
      tools to increase the identification of people who would benefit from palliative
      care is warranted. TRIAL REGISTRATION: PROSPERO CRD42016046564 .

PMID- 28764758
TI  - Does depression moderate handwashing in children?
AB  - BACKGROUND: Although diarrheal diseases are preventable and treatable, they are
      the leading cause of child mortality and morbidity as a consequence of poor
      hygiene and contaminated water. Handwashing with soap is an effective method for
      preventing and decreasing the incidence of diarrhea. However, mental disorders
      such as depression can substantially moderate an individual's ability to cope
      with daily life and can exert a negative influence on daily hygiene activities
      such as handwashing with soap, especially in children. The aim of this study was
      to explain the influence of depression on pupils' hand-washing behavior in
      Zimbabwe. METHODS: In a cross-sectional study, face-to-face interviews were
      carried out with primary school pupils in peri-urban Harare, Zimbabwe (n = 556)
      using a quantitative questionnaire to assess handwashing and its behavioral
      determinants in school settings. The Center for Epidemiological Studies
      Depression Scale for Children (CES-DC) was used to assess depression. RESULTS:
      More than half of the assessed children were depressed. Self-reported handwashing
      with soap among depressed children was significantly lower than among non
      depressed children. Almost all behavioral determinants of hand-washing behavior
      were significantly lower in depressed children. The behavioral determinants
      worked differently in the depressed children than in the non-depressed children's
      group. The effects of important behavioral determinants on handwashing were
      moderated by depression. CONCLUSIONS: Depression exerts a negative influence on
      handwashing in children. These results suggest depression-relieving measures
      should be conducted together with any water, sanitation, and hygiene (WASH)
      interventions to make such interventions more effective.

PMID- 28764759
TI  - Effect of acetic acid on ethanol production by Zymomonas mobilis mutant strains
      through continuous adaptation.
AB  - BACKGROUND: Acetic acid is a predominant by-product of lignocellulosic biofuel
      process, which inhibits microbial biocatalysts. Development of bacterial strains
      that are tolerant to acetic acid is challenging due to poor understanding of the
      underlying molecular mechanisms. RESULTS: In this study, we generated and
      characterized two acetic acid-tolerant strains of Zymomonas mobilis using N
      methyl-N'-nitro-N-nitrosoguanidine (NTG)-acetate adaptive breeding. Two mutants,
      ZMA-142 and ZMA-167, were obtained, showing a significant growth rate at a
      concentration of 244 mM sodium acetate, while the growth of Z. mobilis ATCC 31823
      were completely inhibited in presence of 195 mM sodium acetate. Our data showed
      that acetate-tolerance of ZMA-167 was attributed to a co-transcription of nhaA
      from ZMO0117, whereas the co-transcription was absent in ATCC 31823 and ZMA-142.
      Moreover, ZMA-142 and ZMA-167 exhibited a converstion rate (practical ethanol
      yield to theorical ethanol yield) of 90.16% and 86% at 195 mM acetate-pH 5 stress
      condition, respectively. We showed that acid adaptation of ZMA-142 and ZMA-167 to
      146 mM acetate increased ZMA-142 and ZMA-167 resulted in an increase in ethanol
      yield by 32.21% and 21.16% under 195 mM acetate-pH 5 stress condition,
      respectively. CONCLUSION: The results indicate the acetate-adaptive seed culture
      of acetate-tolerant strains, ZMA-142 and ZMA-167, could enhance the ethanol
      production during fermentation.

PMID- 28764760
TI  - Does weight lifting improve visual acuity? A replication of Gonzalo-Fonrodona and
      Porras (2013).
AB  - OBJECTIVE: A physical effort such as lifting up a weight affects our perception
      and cognition. A previous study reported in two experiments that weight lifting
      improves visual acuity. In the previous study, participants' visual acuity was
      higher while lifting weights than while resting. Moreover, via a case study, that
      study further showed that the heavier the weight, the better the visual acuity.
      These experiments, although interesting, lacked methodological details and
      thorough statistical analyses. We thus conducted experiments similar to these two
      previous ones that mitigated these issues. RESULTS: Although our results of
      Experiment 1 echoed those of the previous study, the results of Experiment 2 did
      not support the latter case report. Thus, our results suggest that the bodily
      experience of weights improves visual acuity, but a gradual increase in weight
      does not seem to lead to a gradual increase in visual acuity.

PMID- 28764761
TI  - Abnormalities in ileal stem, neurogenin 3, and enteroendocrine cells in patients
      with irritable bowel syndrome.
AB  - BACKGROUND: This study examined whether the densities of stem- and
      enteroendocrine cell progenitors are abnormal in the ileum of patients with
      irritable bowel syndrome (IBS), and whether any abnormalities in ileal
      enteroendocrine cells are correlated with abnormalities in stem cells and
      enteroendocrine cell progenitors. METHODS: One hundred and one IBS patients
      covering all IBS subtypes were recruited, and 39 non-IBS subjects were included
      as a control group. The patients and controls underwent standard colonoscopies,
      during which biopsy specimens were obtained from the ileum. The biopsy specimens
      were stained with hematoxylin-eosin and immunostained for Musashi-1 (Msi-1),
      neurogenin 3 (NEUROG3), chromogranin A (CgA), serotonin, peptide YY (PYY),
      oxyntomodulin (enteroglucagon), pancreatic polypeptide, and somatostatin. The
      immunoreactive cells were quantified by computerized image analysis. RESULTS: The
      densities of Msi-1, NEUROG3, CgA, and serotonin cells were reduced in all IBS
      patients and in patients with diarrhea-predominant IBS (IBS-D), mixed-diarrhea
      and-constipation IBS (IBS-M), and constipation-predominant (IBS-C) relative to
      the control subjects. While the PYY cell density was increased in IBS-C relative
      to controls, it did not differ between control subjects and IBS-D and IBS-M
      patients. The densities of Msi-1 and NEUROG3 cells were strongly correlated with
      that of CgA cells. CONCLUSIONS: The abnormalities in the ileal enteroendocrine
      cells appear to be caused by two mechanisms: (1) decreases in the clonogenic
      activity of the stem cells and in the endocrine-cell progenitors differentiating
      into enteroendocrine cells, and (2) switching on the expression of PYY and
      switching off the expression of certain other hormones in other types of the
      enteroendocrine cells.

PMID- 28764762
TI  - Housing conditions of urban households with Aboriginal children in NSW Australia:
      tenure type matters.
AB  - BACKGROUND: Housing is a key determinant of the poor health of Aboriginal
      Australians. Most Aboriginal people live in cities and large towns, yet research
      into housing conditions has largely focused on those living in remote areas. This
      paper measures the prevalence of housing problems amongst participants in a study
      of urban Aboriginal families in New South Wales, Australia, and examines the
      relationship between tenure type and exposure to housing problems. METHODS: Cross
      sectional survey data was provided by 600 caregivers of 1406 Aboriginal children
      aged 0-17 years participating in Phase One of the Study of Environment on
      Aboriginal Resilience and Child Health (SEARCH). Regression modelling of the
      associations between tenure type (own/mortgage, private rental or social housing)
      and housing problems was conducted, adjusting for sociodemographic factors.
      RESULTS: The majority (60%) of SEARCH households lived in social housing, 21%
      rented privately and 19% either owned their home outright or were paying a
      mortgage ("owned"). Housing problems were common, particularly structural
      problems, damp and mildew, vermin, crowding and unaffordability. Physical
      dwelling problems were most prevalent for those living in social housing, who
      were more likely to report three or more physical dwelling problems than those in
      owned (PR 3.19, 95%CI 1.97, 5.73) or privately rented homes (PR 1.49, 1.11,
      2.08). However, those in social housing were the least likely to report
      affordability problems. Those in private rental moved home most frequently;
      children in private rental were more than three times as likely to have lived in
      four or more homes since birth than those in owned homes (PR 3.19, 95%CI 1.97,
      5.73). Those in social housing were almost half as likely as those in private
      rental to have lived in four or more homes since birth (PR 0.56, 95%CI 0.14,
      0.77). Crowding did not vary significantly by tenure type. CONCLUSIONS: The high
      prevalence of housing problems amongst study participants suggests that urban
      Aboriginal housing requires further attention as part of efforts to reduce the
      social and health disadvantage experienced by Aboriginal Australians. Particular
      attention should be directed to the needs of those renting in the private and
      social housing sectors, who are experiencing the poorest dwelling conditions.

PMID- 28764763
TI  - The shrinking health advantage: unintentional injuries among children and youth
      from immigrant families.
AB  - BACKGROUND: Immigrants typically arrive in good health. This health benefit can
      decline as immigrants adopt behaviours similar to native-born populations. Risk
      of injury is low in immigrants but it is not known whether this changes with
      increasing time since migration. We sought to examine the association between
      duration of residence in Canada and risk of unintentional injury. METHODS:
      Population-based cross-sectional study of children and youth 0 to 24 years in
      Ontario, Canada (2011-2012), using linked health and administrative databases.
      The main exposure was duration of Canadian residence (recent: 0-5 years,
      intermediate: 6-10 years, long-term: >10 years). The main outcome measure was
      unintentional injuries. Cause-specific injury risk by duration of residence was
      also evaluated. Poisson regression models estimated rate ratios (RR) for
      injuries. RESULTS: 999951 immigrants were included with 24.2% recent and 26.4%
      intermediate immigrants. The annual crude injury rates per 100000 immigrants were
      6831 emergency department visits, 151 hospitalizations, and 4 deaths. In adjusted
      models, recent immigrants had the lowest risk of injury and risk increased over
      time (RR 0.79; 95% CI 0.77, 0.81 recent immigrants, RR 0.90; 95% CI 0.88, 0.92
      intermediate immigrants, versus long-term immigrants). Factors associated with
      injury included young age (0-4 years, RR 1.30; 95% CI 1.26, 1.34), male sex (RR
      1.52; 95% CI 1.49, 1.55), and high income (RR 0.93; 95% CI 0.89, 0.96 quintile 1
      versus 5). Longer duration of residence was associated with a higher risk of
      unintentional injuries for most causes except hot object/scald burns, machinery
      related injuries, non-motor vehicle bicycle and pedestrian injuries. The risk of
      these latter injuries did not change significantly with increasing duration of
      residence in Canada. Risk of drowning was highest in recent immigrants.
      CONCLUSIONS: Risk of all-cause and most cause-specific unintentional injuries in
      immigrants rises with increasing time since migration. This indicates the need to
      develop strategies for maintaining the immigrant health advantage over time while
      balancing the desire to support integration, active living, and healthy child
      development.

PMID- 28764764
TI  - Sclerosing mesenteritis in a 5-year-old Chinese boy: a case report.
AB  - BACKGROUND: Sclerosing mesenteritis is a rare fibroinflammatory disorder of
      unknown etiology that primarily affects the mesentery of the small intestine
      during late adult life. Only about twenty pediatric cases have been reported to
      date, but none has been reported in Chinese children. CASE PRESENTATION: A 5-year
      old Chinese male presented with a 4-week history of recurrent bloating, abdominal
      pain, anorexia and vomiting. On admission, physical examination showed a severely
      distended abdomen. Biochemical investigations showed a slightly increased C
      reactive protein, and normal serum levels of electrolytes and erythrocyte
      sedimentation rate. An abdominal film showed small intestine obstruction and
      massive ascites. An exploratory laparotomy revealed widespread inflammatory
      fibrotic adhesions between the bowel and the abdominal wall, thickening of the
      small bowel and massive ascites. During a prolonged hospital course, a 2nd
      surgery (4 months after 1st exploratory laparotomy) was performed in order to
      close the ileostomy and revealed that the bowel was still severely edematous,
      with very tight adhesions between the bowel and the abdominal wall.
      Histopathological examination of excised mesentery and nodules showed chronic
      inflammatory cell infiltration, fat necrosis and fibrosis. A diagnosis of
      sclerosing mesenteritis was finally established. Prednisolone at 2 mg/kg was
      started and he experienced rapid clinical improvement in 4 weeks. CONCLUSIONS:
      Sclerosing mesenteritis is extremely rare in children and often misdiagnosed due
      to its nonspecific clinical manifestation. It is important to be aware of
      sclerosing mesenteritis when evaluating a child with intractable abdominal pain,
      bloating, intestinal obstruction and massive ascites.

PMID- 28764765
TI  - Late-phase immune responses limiting oocyst survival are independent of TEP1
      function yet display strain specific differences in Anopheles gambiae.
AB  - BACKGROUND: There is emerging evidence that mosquito anti-Plasmodium immunity is
      multimodal with distinct mechanisms for killing malaria parasites at either the
      ookinete or oocyst stages. Early-phase responses targeting the ookinete require
      complement-like components circulating in the mosquito hemolymph that result in
      TEP1-mediated lysis or melanization. Additional responses mediated by the LL3 and
      STAT pathways limit oocyst survival through unknown mechanisms that require
      mosquito hemocyte function. While previous experiments argue that these
      mechanisms of parasite killing are independent, the transient nature of gene
      silencing has rendered these experiments inconclusive. To address this issue, we
      outline experiments using a TALEN-derived TEP1 mutant line to examine the role of
      TEP1 in the Anopheles gambiae late-phase immune response. RESULTS: Despite higher
      early oocyst numbers in the TEP1 mutant line, no differences in oocyst survival
      were observed when compared to control mosquitoes, suggesting that TEP1 function
      is independent of the late-phase immune response. To further validate this
      phenotype in the TEP1 mutant, oocyst survival was evaluated in the TEP1 mutant
      background by silencing either LL3 or STAT-A. Surprisingly, only STAT-A silenced
      mosquitoes were able to reconstitute the late-phase immune phenotype increasing
      oocyst survival in the TEP1 mutant line. Additional experiments highlight
      significant differences in LL3 expression in the M/S hybrid genetic background of
      the TEP1 mutant line compared to that of the Keele strain (M form) of An.
      gambiae, and demonstrate that LL3 is not required for granulocyte differentiation
      in the M/S hybrid G3 genetic background in response to malaria parasite
      infection. CONCLUSIONS: Through the combination of genetic experiments utilizing
      genetic mutants and reverse genetic approaches, new information has emerged
      regarding the mechanisms of mosquito late-phase immunity. When combined with
      previously published experiments, the body of evidence argues that Plasmodium
      oocyst survival is TEP1 independent, thus establishing that the mechanisms of
      early- and late-phase immunity are distinct. Moreover, we identify that the known
      components that mediate oocyst survival are susceptible to strain-specific
      differences depending on their genetic background and provide further evidence
      that the signals that promote hemocyte differentiation are required to limit
      oocyst survival. Together, this study provides new insights into the mechanisms
      of oocyst killing and the importance of genetics in shaping mosquito vector
      competence.

PMID- 28764766
TI  - Physicians' pharmacogenomics information needs and seeking behavior: a study with
      case vignettes.
AB  - BACKGROUND: Genetic testing, especially in pharmacogenomics, can have a major
      impact on patient care. However, most physicians do not feel that they have
      sufficient knowledge to apply pharmacogenomics to patient care. Online
      information resources can help address this gap. We investigated physicians'
      pharmacogenomics information needs and information-seeking behavior, in order to
      guide the design of pharmacogenomics information resources that effectively meet
      clinical information needs. METHODS: We performed a formative, mixed-method
      assessment of physicians' information-seeking process in three pharmacogenomics
      case vignettes. Interactions of 6 physicians' with online pharmacogenomics
      resources were recorded, transcribed, and analyzed for prominent themes.
      Quantitative data included information-seeking duration, page navigations, and
      number of searches entered. RESULTS: We found that participants searched an
      average of 8 min per case vignette, spent less than 30 s reviewing specific
      content, and rarely refined search terms. Participants' information needs
      included a need for clinically meaningful descriptions of test interpretations, a
      molecular basis for the clinical effect of drug variation, information on the
      logistics of carrying out a genetic test (including questions related to cost,
      availability, test turn-around time, insurance coverage, and accessibility of
      expert support).Also, participants sought alternative therapies that would not
      require genetic testing. CONCLUSION: This study of pharmacogenomics information
      seeking behavior indicates that content to support their information needs is
      dispersed and hard to find. Our results reveal a set of themes that information
      resources can use to help physicians find and apply pharmacogenomics information
      to the care of their patients.

PMID- 28764767
TI  - Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with
      gamma-secretase and regulates neuronal amyloid beta-peptide levels.
AB  - BACKGROUND: Increased levels of the pathogenic amyloid beta-peptide (Abeta),
      released from its precursor by the transmembrane protease gamma-secretase, are
      found in Alzheimer disease (AD) brains. Interestingly, monoamine oxidase B (MAO
      B) activity is also increased in AD brain, but its role in AD pathogenesis is not
      known. Recent neuroimaging studies have shown that the increased MAO-B expression
      in AD brain starts several years before the onset of the disease. Here, we show a
      potential connection between MAO-B, gamma-secretase and Abeta in neurons.
      METHODS: MAO-B immunohistochemistry was performed on postmortem human brain.
      Affinity purification of gamma-secretase followed by mass spectrometry was used
      for unbiased identification of gamma-secretase-associated proteins. The
      association of MAO-B with gamma-secretase was studied by coimmunoprecipitation
      from brain homogenate, and by in-situ proximity ligation assay (PLA) in neurons
      as well as mouse and human brain sections. The effect of MAO-B on Abeta
      production and Notch processing in cell cultures was analyzed by siRNA silencing
      or overexpression experiments followed by ELISA, western blot or FRET analysis.
      Methodology for measuring relative intraneuronal MAO-B and Abeta42 levels in
      single cells was developed by combining immunocytochemistry and confocal
      microscopy with quantitative image analysis. RESULTS: Immunohistochemistry
      revealed MAO-B staining in neurons in the frontal cortex, hippocampus CA1 and
      entorhinal cortex in postmortem human brain. Interestingly, the neuronal staining
      intensity was higher in AD brain than in control brain in these regions. Mass
      spectrometric data from affinity purified gamma-secretase suggested that MAO-B is
      a gamma-secretase-associated protein, which was confirmed by immunoprecipitation
      and PLA, and a neuronal location of the interaction was shown. Strikingly,
      intraneuronal Abeta42 levels correlated with MAO-B levels, and siRNA silencing of
      MAO-B resulted in significantly reduced levels of intraneuronal Abeta42.
      Furthermore, overexpression of MAO-B enhanced Abeta production. CONCLUSIONS: This
      study shows that MAO-B levels are increased not only in astrocytes but also in
      pyramidal neurons in AD brain. The study also suggests that MAO-B regulates Abeta
      production in neurons via gamma-secretase and thereby provides a key to
      understanding the relationship between MAO-B and AD pathogenesis. Potentially,
      the gamma-secretase/MAO-B association may be a target for reducing Abeta levels
      using protein-protein interaction breakers.

PMID- 28764768
TI  - More than a virus: a qualitative study of the social implications of hepatitis B
      infection in China.
AB  - BACKGROUND: China has the largest absolute number of people living with hepatitis
      B with up to 300,000 people estimated to die each year from hepatitis B related
      diseases. Despite advances in immunisation, clinical management, and health
      policy, there is still a lack of accessible and affordable health care for people
      with hepatitis B. Through in-depth interviews, this study identifies the
      personal, social and economic impact of living with hepatitis B and considers the
      role of stigma and discrimination as barriers to effective clinical management of
      the disease. METHODS: Semi-structured qualitative interviews were held with 41
      people living with hepatitis B in five Chinese cities. Participants were
      recruited through clinical and non-government organisations providing services to
      people with hepatitis B, with most (n = 32) being under the age of 35 years.
      RESULTS: People living with hepatitis B experience the disease as a
      transformative intergenerational chronic infection with multiple personal and
      social impacts. These include education and employment choices, economic
      opportunities, and the development of intimate relationships. While regulations
      reducing access to employment and education for people with hepatitis B have been
      repealed, stigma and discrimination continue to marginalise people with hepatitis
      B. CONCLUSIONS: Effective public policy to reduce morbidity and mortality
      associated with hepatitis B needs to address the lived impact of hepatitis B on
      families, employment and educational choices, finances, and social
      marginalisation.

PMID- 28764769
TI  - Anabolic role of lysyl oxidase like-2 in cartilage of knee and temporomandibular
      joints with osteoarthritis.
AB  - BACKGROUND: Lysyl oxidase like-2 (LOXL2) is a copper-dependent amine oxidase. Our
      previous studies showed that LOXL2 is elevated during mouse fracture healing. The
      goal of this study was to evaluate the potential of LOXL2 to act as an anabolic
      agent in cartilage affected by osteoarthritis (OA). METHODS: LOXL2 was visualized
      in tissues from human knee and hip joints and temporomandibular joints (TMJ) by
      immunofluorescence. The activity of LOXL2 in human articular and TMJ chondrocytes
      was assessed by cell-based assays, microarray analysis, and RT-qPCR, and LOXL2
      mediated activation of NF-kappaB and extracellular signal-related kinase (ERK)
      signaling pathways was measured by western blotting. To examine LOXL2-induced
      effect in vivo, we implanted Matrigel-imbedded human chondrocytes into nude mice
      and exposed them to exogenous LOXL2 for 6 weeks. Finally, LOXL2-induced effects
      on collagen type 2 alpha1 (COL2A1) and phospho-SMAD2/3 were evaluated by
      immunofluorescence analysis. RESULTS: LOXL2 staining was detected in damaged
      regions of human TMJ, hip and knee joints affected by OA. Stimulation with
      transforming growth factor (TGF)-beta1 upregulated LOXL2 expression, while pro
      inflammatory cytokines IL-1beta and TNF-alpha downregulated LOXL2, in human
      chondrocytes. Viral transduction of LOXL2 in OA chondrocytes increased the mRNA
      levels of chondroitin sulfate proteoglycan (CSPG4), aggrecan (ACAN), sex
      determining region Y-box containing gene 9 (SOX9), and COL2A1 but reduced the
      levels of extracellular matrix (ECM)-degrading enzymes matrix metalloproteinase
      (MMP)1, MMP3, and MMP13. Further, forced expression of LOXL2 promoted
      chondrogenic lineage-specific gene expression, increased the expression of COL2A1
      in the presence of TNF-alpha, and inhibited chondrocyte apoptosis. LOXL2
      expression also inhibited IL-1beta-induced phospho-NF-kappaB/p65 and TGF-beta1
      induced ERK1/2 phosphorylation. Matrigel constructs of human chondrocytes from
      the knee joint and TMJ implanted in nude mice showed anabolic responses after
      LOXL2 transduction, including increased expression of SOX9, ACAN, and COL2A1.
      Finally, immunofluorescence staining revealed co-localization of LOXL2 with SOX9
      in the nuclei of cells in the implants, decreased phospho-SMAD2/3, and increased
      COL2A1 staining. CONCLUSION: Our results suggest that although LOXL2 is
      upregulated in cartilage affected by OA, this may be a protective response that
      promotes anabolism while inhibiting specific catabolic responses in the
      pathophysiology of OA.

PMID- 28764770
TI  - Psychometric properties of the short Warwick Edinburgh mental well-being scale
      (SWEMWBS) in service users with schizophrenia, depression and anxiety spectrum
      disorders.
AB  - BACKGROUND: To establish the validity and reliability of the Short Warwick
      Edinburgh Mental Well-being Scale (SWEMWBS) in service users with schizophrenia,
      depression and anxiety spectrum disorders in Singapore and estimate SWEMWBS
      scores across socio-demographic and the three psychiatric diagnostic groups in
      the sample. METHODS: This secondary analysis was conducted using data from a
      study among outpatients of a tertiary psychiatric hospital. In addition to the
      SWEMWBS, socio-demographic data and current psychiatric diagnosis were collected.
      Service users were also administered the Global Assessment of Functioning (GAF),
      Patient Health Questionnaire (PHQ)-8, Generalised Anxiety Disorder (GAD)-7,
      Satisfaction with Life Scale (SWLS) and the Positive Mental Health (PMH)
      instrument. The SWEMWBS was tested for factorial validity, reliability and
      convergent and divergent validity. RESULTS: In total, 350 service users with a
      mean (SD) age of 39.1 (11.1) years were included in this study of which 39.4%,
      38.9% and 21.7% had schizophrenia, depression and anxiety spectrum disorders,
      respectively. The single factor structure of the SWEMWBS was confirmed by
      confirmatory factor analysis (CFI = 0.969, TLI = 0.954, RMSEA = 0.029). The
      internal consistency reliability was high (Cronbach's alpha = 0.89). The
      convergent and divergent validity testing revealed that the SWEMWBS scores had
      significant moderate to high positive correlations with GAF, SWLS and PMH scores
      and moderate negative correlations with (PHQ)-8 and (GAD)-7 scores. SWEMWBS
      scores were higher in married participants (22.2 (5.4) versus never married: 20.7
      (5.3) and divorced/separated/widowed: 20.4 (5.1), p = 0.049) and among those with
      schizophrenia (22.8 (5.5) versus depression:19.6 (4.7) and anxiety spectrum
      disorders 20.9 (5.2), p < 0.001). CONCLUSION: These results demonstrate adequate
      validity and reliability of the SWEMWBS in people with schizophrenia, depression
      and anxiety spectrum disorders in Singapore.

PMID- 28764771
TI  - Sensitivity of restriction spectrum imaging to memory and neuropathology in
      Alzheimer's disease.
AB  - BACKGROUND: Diffusion imaging has demonstrated sensitivity to structural brain
      changes in Alzheimer's disease (AD). However, there remains a need for a more
      complete characterization of microstructural alterations occurring at the
      earliest disease stages, and how these changes relate to underlying
      neuropathology. This study evaluated the sensitivity of restriction spectrum
      imaging (RSI), an advanced diffusion magnetic resonance imaging (MRI) technique,
      to microstructural brain changes in mild cognitive impairment (MCI) and AD.
      METHODS: MRI and neuropsychological test data were acquired from 31 healthy
      controls, 12 individuals with MCI, and 13 individuals with mild AD, aged 63-93
      years. Cerebrospinal fluid amyloid-beta levels were measured in a subset (n = 38)
      of participants. RSI measures of neurite density (ND) and isotropic free water
      (IF) were computed in fiber tracts and in hippocampal and entorhinal cortex gray
      matter, respectively. Analyses evaluated whether these measures predicted memory
      performance, correlated with amyloid-beta levels, and distinguished impaired
      individuals from controls. For comparison, analyses were repeated with standard
      diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean
      diffusivity. RESULTS: Both RSI and DTI measures correlated with episodic memory
      and disease severity. RSI, but not DTI, measures correlated with amyloid-beta42
      levels. ND and FA in the arcuate fasciculus and entorhinal cortex IF most
      strongly predicted recall performance. RSI measures of arcuate fasciculus ND and
      entorhinal cortex IF best discriminated memory impaired participants from healthy
      participants. CONCLUSIONS: RSI is highly sensitive to microstructural changes in
      the early stages of AD, and is associated with biochemical markers of AD
      pathology. Reduced ND in cortical association fibers and increased medial
      temporal lobe free-water diffusion predicted episodic memory, distinguished
      cognitively impaired from healthy individuals, and correlated with amyloid-beta.
      Although further research is needed to assess the sensitivity of RSI to
      preclinical AD and disease progression, these results suggest that RSI may be a
      promising tool to better understand neuroanatomical changes in AD and their
      association with neuropathology.

PMID- 28764772
TI  - Phlebotomine sand fly survey in the focus of leishmaniasis in Madrid, Spain (2012
      2014): seasonal dynamics, Leishmania infantum infection rates and blood meal
      preferences.
AB  - BACKGROUND: An unusual increase of human leishmaniasis cases due to Leishmania
      infantum is occurring in an urban area of southwestern Madrid, Spain, since 2010.
      Entomological surveys have shown that Phlebotomus perniciosus is the only
      potential vector. Direct xenodiagnosis in hares (Lepus granatensis) and rabbits
      (Oryctolagus cuniculus) collected in the focus area proved that they can transmit
      parasites to colonized P. perniciosus. Isolates were characterized as L.
      infantum. The aim of the present work was to conduct a comprehensive study of
      sand flies in the outbreak area, with special emphasis on P. perniciosus.
      METHODS: Entomological surveys were done from June to October 2012-2014 in 4
      stations located close to the affected area. Twenty sticky traps (ST) and two CDC
      light traps (LT) were monthly placed during two consecutive days in every
      station. LT were replaced every morning. Sand fly infection rates were determined
      by dissecting females collected with LT. Molecular procedures applied to study
      blood meal preferences and to detect L. infantum were performed for a better
      understanding of the epidemiology of the outbreak. RESULTS: A total of 45,127
      specimens belonging to 4 sand fly species were collected: P. perniciosus
      (75.34%), Sergentomyia minuta (24.65%), Phlebotomus sergenti (0.005%) and
      Phlebotomus papatasi (0.005%). No Phlebotomus ariasi were captured. From 3203 P.
      perniciosus female dissected, 117 were infected with flagellates (3.7%).
      Furthermore, 13.31% and 7.78% of blood-fed and unfed female sand flies,
      respectively, were found infected with L. infantum by PCR. The highest rates of
      infected P. perniciosus were detected at the end of the transmission periods.
      Regarding to blood meal preferences, hares and rabbits were preferred, although
      human, cat and dog blood were also found. CONCLUSIONS: This entomological study
      highlights the exceptional nature of the Leishmania outbreak occurring in
      southwestern Madrid, Spain. It is confirmed that P. perniciosus is the only
      vector in the affected area, with high densities and infection rates. Rabbits and
      hares were the main blood meal sources of this species. These results reinforce
      the need for an extensive and permanent surveillance in this region, and others
      of similar characteristics, in order to control the vector and regulate the
      populations of wild reservoirs.

PMID- 28764773
TI  - Quantification of both the area-at-risk and acute myocardial infarct size in ST
      segment elevation myocardial infarction using T1-mapping.
AB  - BACKGROUND: A comprehensive cardiovascular magnetic resonance (CMR) in reperfused
      ST-segment myocardial infarction (STEMI) patients can be challenging to perform
      and can be time-consuming. We aimed to investigate whether native T1-mapping can
      accurately delineate the edema-based area-at-risk (AAR) and post-contrast T1
      mapping and synthetic late gadolinium (LGE) images can quantify MI size at 1.5 T.
      Conventional LGE imaging and T2-mapping could then be omitted, thereby shortening
      the scan duration. METHODS: Twenty-eight STEMI patients underwent a CMR scan at
      1.5 T, 3 +/- 1 days following primary percutaneous coronary intervention. The AAR
      was quantified using both native T1 and T2-mapping. MI size was quantified using
      conventional LGE, post-contrast T1-mapping and synthetic magnitude-reconstructed
      inversion recovery (MagIR) LGE and synthetic phase-sensitive inversion recovery
      (PSIR) LGE, derived from the post-contrast T1 maps. RESULTS: Native T1-mapping
      performed as well as T2-mapping in delineating the AAR (41.6 +/- 11.9% of the
      left ventricle [% LV] versus 41.7 +/- 12.2% LV, P = 0.72; R2 0.97; ICC 0.986
      (0.969-0.993); bias -0.1 +/- 4.2% LV). There were excellent correlation and inter
      method agreement with no bias, between MI size by conventional LGE, synthetic
      MagIR LGE (bias 0.2 +/- 2.2%LV, P = 0.35), synthetic PSIR LGE (bias 0.4 +/- 2.2%
      LV, P = 0.060) and post-contrast T1-mapping (bias 0.3 +/- 1.8% LV, P = 0.10). The
      mean scan duration was 58 +/- 4 min. Not performing T2 mapping (6 +/- 1 min) and
      conventional LGE (10 +/- 1 min) would shorten the CMR study by 15-20 min.
      CONCLUSIONS: T1-mapping can accurately quantify both the edema-based AAR (using
      native T1 maps) and acute MI size (using post-contrast T1 maps) in STEMI patients
      without major cardiovascular risk factors. This approach would shorten the
      duration of a comprehensive CMR study without significantly compromising on data
      acquisition and would obviate the need to perform T2 maps and LGE imaging.

PMID- 28764774
TI  - 'Sly grog' and 'homebrew': a qualitative examination of illicit alcohol and some
      of its impacts on Indigenous communities with alcohol restrictions in regional
      and remote Queensland (Australia).
AB  - BACKGROUND: Indigenous communities in Queensland (Australia) have been subject to
      Alcohol Management Plans since 2002/03, with significant penalties for breaching
      restrictions. 'Sly grog' and 'homebrew' provide access to alcohol despite
      restrictions. This paper describes how this alcohol is made available and the
      risks and impacts involved. In affected towns and communities across a large area
      of rural and remote Queensland, interviews and focus groups documented
      experiences and views of 255 long-standing community members and service
      providers. Using an inductive framework, transcribed interviews were analysed to
      identify supply mechanisms, community and service provider responses and impacts
      experienced. RESULTS: 'Homebrew' was reportedly manufactured in just a few
      localities, in locally-specific forms bringing locally-specific harms. However,
      'sly grog' sourced from licensed premises located long distances from
      communities, is a widespread concern across the region. 'Sly grog' sellers
      circumvent retailers' takeaway liquor license conditions, stockpile alcohol
      outside restricted areas, send hoax messages to divert enforcement and take
      extraordinary risks to avoid apprehension. Police face significant challenges to
      enforce restrictions. On-selling of 'sly grog' appears more common in remote
      communities with total prohibition. Despite different motives for involvement in
      an illicit trade 'sly grog' consumers and sellers receive similar penalties.
      CONCLUSIONS: There is a need for: (a) a more sophisticated regional approach to
      managing takeaway alcohol sales from licensed suppliers, (b) targeted penalties
      for 'sly grog' sellers that reflect its significant community impact,

PMID- 28764775
TI  - An assessment on the role of endophytic microbes in the therapeutic potential of
      Fagonia indica.
AB  - BACKGROUND: Natural products of animals, plants and microbes are potential source
      of important chemical compounds, with diverse applications including
      therapeutics. Endophytic bacteria that are especially associated with medicinal
      plants presents a reservoir of therapeutic compounds. Fagonia indica has been
      recently investigated by numerous researchers because of its striking therapeutic
      potential especially in cancer. It is also reported that endophytes play a vital
      role in the biosynthesis of various metabolites; therefore we believe that
      endophytes associated with F. indica are of crucial importance in this regard.
      The present study aims successful isolation, molecular identification of
      endophytic bacteria and their screening for bioactive metabolites quantification
      and in vitro pharmacological activities. METHODS: 16S rRNA gene sequencing was
      used for the identification of isolated endophytic bacteria. Methanolic extracts
      were evaluated for total phenolic contents (TPC), total flavonoids contents
      (TFC), DPPH free radical scavenging activity, reducing power and total anti
      oxidant assays were performed. And also screened for antibacterial and antifungal
      activities by disc diffusion method and their MIC were calculated by broth
      dilution method using microplate reader. Further, standard protocols were
      followed for antileishmanial activity and protein kinase inhibition. Analysis and
      statistics were performed using SPSS, Table curve and Origin 8.5 for graphs.
      RESULTS: Bacterial strains belonging to various genera (Bacillus, Enterobacter,
      Pantoea, Erwinia and Stenotrophomonas) were isolated and identified. Total
      phenolic contents and total flavonoids contents varies among all the bacterial
      extracts respectively in which Bacillus subtilis showed high phenolic contents
      243 ug/mg of gallic acid equivalents (GAE) and Stenotrophomonas maltophilia
      showed high flavonoids contents 15.9 ug/mg quercitin equivalents (QA), total
      antioxidant capacity (TAC) 37.6 ug/mg of extract, reducing power (RP) 206 ug/mg
      of extract and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging
      activity with 98.7 MUg/mL IC50 value. Although all the extracts tested were
      active to inhibit growth of selected pathogenic microbes (bacteria and fungi),
      but significant antibacterial activity was observed against Klebsiella pneumonia
      and B. subtilis. An Enterobacter cloaca was active against Leishmania tropica
      with IC50 value of 1.4 ug/mg extracts. B. subtilis and Bacillus tequilensis
      correspondingly exhibit significant protein kinase inhibition of 47 +/- 0.72 and
      42 +/- 1.21 mm bald zones, indicating anti-infective and antitumor potential.
      CONCLUSIONS: Our findings revealed that crude extracts of selected endophytic
      bacteria from F. indica possess excellent biological activities indicating their
      potential as an important source of antibiotics (antifungal, antibacterial)
      compounds.

PMID- 28764776
TI  - Costs of health care across primary care models in Ontario.
AB  - BACKGROUND: The purpose of this study is to analyze the relationship between
      newly introduced primary care models in Ontario, Canada, and patients' primary
      care and total health care costs. A specific focus is on the payment mechanisms
      for primary care physicians, i.e. fee-for-service (FFS), enhanced-FFS, and
      blended capitation, and whether providers practiced as part of a
      multidisciplinary team. METHODS: Utilization data for a one year period was
      measured using administrative databases for a 10% sample selected at random from
      the Ontario adult population. Primary care and total health care costs were
      calculated at the individual level and included costs from physician services,
      hospital visits and admissions, long term care, drugs, home care, lab tests, and
      visits to non-medical health care providers. Generalized linear model regressions
      were conducted to assess the differences in costs between primary care models.
      RESULTS: Patients not enrolled with a primary care physicians were younger, more
      likely to be males and of lower socio-economic status. Patients in blended
      capitation models were healthier and wealthier than FFS and enhanced-FFS
      patients. Primary care and total health care costs were significantly different
      across Ontario primary care models. Using the traditional FFS as the reference,
      we found that patients in the enhanced-FFS models had the lowest total health
      care costs, and also the lowest primary care costs. Patients in the blended
      capitation models had higher primary care costs but lower total health care
      costs. Patients that were in multidisciplinary teams (FHT), where physicians are
      also paid on a blended capitation basis, had higher total health care costs than
      non-FHT patients but still lower than the FFS reference group. Primary care and
      total health care costs increased with patients' age, morbidity, and lower income
      quintile across all primary care payment types. CONCLUSIONS: The new primary care
      models were associated with lower total health care costs for patients compared
      to the traditional FFS model, despite higher primary care costs in some models.

PMID- 28764777
TI  - Betamethasone gel compared with lidocaine jelly to reduce tracheal tube related
      postoperative airway symptoms: a randomized controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Post-operative airway symptoms can be troublesome to
      patients following an uneventful general anesthesia with endotracheal intubation.
      In this study, we compared the effectiveness of lubricating an endotracheal tube
      with betamethasone gel or lidocaine jelly with using an unlubricated tube in
      reducing the incidence and severity of postoperative sore throat, hoarseness and
      cough. METHODS: This was a prospective, randomized, single-blind comparative
      study carried out among 120 ASA I and II patients aged 18-65 years undergoing
      elective surgery under general anesthesia with endotracheal intubation. Patients
      were randomly divided into three groups of 40 patients each. Endotracheal tube
      used for patients in group C was unlubricated, while that for group B and group L
      were lubricated up to 15 cm mark with 2.5 ml of 0.05% betamethasone gel or 2%
      lidocaine jelly respectively. Incidence and severity of postoperative sore
      throat, hoarseness and cough were observed at 1, 6 and 24 h following extubation.
      RESULTS: At 24 h following extubation, group B had the lowest incidence of
      postoperative sore throat among the three groups (group B: 12.5% vs group L:
      37.5% vs group C: 25%; p = 0.036). Severity of postoperative sore throat at 24 h
      was less with betamethasone (score 0: 87.5%, 1: 10%) compared with lidocaine
      (score 0: 62.5%, 1: 37.5%) and control (score 0:75%, 1: 20%) (p = 0.006).
      Observations at other times and of other variables were comparable. CONCLUSION:
      Wide spread application of 0.05% betamethasone gel to lubricate the endotracheal
      tube significantly reduces the incidence and severity of sore throat at 24 h of
      extubation but not of hoarseness or cough.

PMID- 28764778
TI  - Centella asiatica modulates cancer cachexia associated inflammatory cytokines and
      cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells
      (PBMC's).
AB  - BACKGROUND: Cancer cachexia is associated with increased pro-inflammatory
      cytokine levels. Centella asiatica (C. asiatica) possesses antioxidant, anti
      inflammatory and anti-tumour potential. We investigated the modulation of
      antioxidants, cytokines and cell death by C. asiatica ethanolic leaf extract
      (CLE) in leukaemic THP-1 cells and normal peripheral blood mononuclear cells
      (PBMC's). METHODS: Cytotoxcity of CLE was determined at 24 and 72 h (h). Oxidant
      scavenging activity of CLE was evaluated using the 2, 2-diphenyl-1 picrylhydrazyl
      (DPPH) assay. Glutathione (GSH) levels, caspase (-8, -9, -3/7) activities and
      adenosine triphosphate (ATP) levels (Luminometry) were then assayed. The levels
      of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-1beta and IL
      10 were also assessed using enzyme-linked immunosorbant assay. RESULTS: CLE
      decreased PBMC viability between 33.25-74.55% (24 h: 0.2-0.8 mg/ml CLE and 72 h:
      0.4-0.8 mg/ml CLE) and THP-1 viability by 28.404% (72 h: 0.8 mg/ml CLE) (p <
      0.0001). Oxidant scavenging activity was increased by CLE (0.05-0.8 mg/ml) (p <
      0.0001). PBMC TNF-alpha and IL-10 levels were decreased by CLE (0.05-0.8 mg/ml)
      (p < 0.0001). However, PBMC IL-6 and IL-1beta concentrations were increased at
      0.05-0.2 mg/ml CLE but decreased at 0.4 mg/ml CLE (p < 0.0001). In THP-1 cells,
      CLE (0.2-0.8 mg/ml) decreased IL-1beta and IL-6 whereas increased IL-10 levels (p
      < 0.0001). In both cell lines, CLE (0.05-0.2 mg/ml, 24 and 72 h) increased GSH
      concentrations (p < 0.0001). At 24 h, caspase (-9, -3/7) activities was increased
      by CLE (0.05-0.8 mg/ml) in PBMC's whereas decreased by CLE (0.2-0.4 mg/ml) in THP
      1 cells (p < 0.0001). At 72 h, CLE (0.05-0.8 mg/ml) decreased caspase (-9, -3/7)
      activities and ATP levels in both cell lines (p < 0.0001). CONCLUSION: In PBMC's
      and THP-1 cells, CLE proved to effectively modulate antioxidant activity,
      inflammatory cytokines and cell death. In THP-1 cells, CLE decreased pro
      inflammatory cytokine levels whereas it increased anti-inflammatory cytokine
      levels which may alleviate cancer cachexia.

PMID- 28764779
TI  - The influence of the team in conducting a systematic review.
AB  - There is an increasing body of research documenting flaws in many published
      systematic reviews' methodological and reporting conduct. When good systematic
      review practice is questioned, attention is rarely turned to the composition of
      the team that conducted the systematic review. This commentary highlights a
      number of relevant articles indicating how the composition of the review team
      could jeopardise the integrity of the systematic review study and its
      conclusions. Key biases require closer attention such as sponsorship bias and
      researcher allegiance, but there may also be less obvious affiliations in teams
      conducting secondary evidence-syntheses. The importance of transparency and
      disclosure are now firmly on the agenda for clinical trials and primary research,
      but the meta-biases that systematic reviews may be at risk from now require
      further scrutiny.

PMID- 28764780
TI  - Improving patient safety culture in Saudi Arabia (2012-2015): trending,
      improvement and benchmarking.
AB  - BACKGROUND: Measuring patient safety culture can provide insight into areas for
      improvement and help monitor changes over time. This study details the findings
      of a re-assessment of patient safety culture in a multi-site Medical City in
      Riyadh, Kingdom of Saudi Arabia (KSA). Results were compared to an earlier
      assessment conducted in 2012 and benchmarked with regional and international
      studies. Such assessments can provide hospital leadership with insight on how
      their hospital is performing on patient safety culture composites as a result of
      quality improvement plans. This paper also explored the association between
      patient safety culture predictors and patient safety grade, perception of patient
      safety, frequency of events reported and number of events reported. METHODS: We
      utilized a customized version of the patient safety culture survey developed by
      the Agency for Healthcare Research and Quality. The Medical City is a tertiary
      care teaching facility composed of two sites (total capacity of 904 beds). Data
      was analyzed using SPSS 24 at a significance level of 0.05. A t-Test was used to
      compare results from the 2012 survey to that conducted in 2015. Two adopted
      Generalized Estimating Equations in addition to two linear models were used to
      assess the association between composites and patient safety culture outcomes.
      Results were also benchmarked against similar initiatives in Lebanon, Palestine
      and USA. RESULTS: Areas of strength in 2015 included Teamwork within units, and
      Organizational Learning-Continuous Improvement; areas requiring improvement
      included Non-Punitive Response to Error, and Staffing. Comparing results to the
      2012 survey revealed improvement on some areas but non-punitive response to error
      and Staffing remained the lowest scoring composites in 2015. Regression
      highlighted significant association between managerial support, organizational
      learning and feedback and improved survey outcomes. Comparison to international
      benchmarks revealed that the hospital is performing at or better than benchmark
      on several composites. CONCLUSION: The Medical City has made significant progress
      on several of the patient safety culture composites despite still having areas
      requiring additional improvement. Patient safety culture outcomes are evidently
      linked to better performance on specific composites. While results are comparable
      with regional and international benchmarks, findings confirm that regular
      assessment can allow hospitals to better understand and visualize changes in
      their performance and identify additional areas for improvement.

PMID- 28764781
TI  - Effects of the combined extracts of Herba Epimedii and Fructus Ligustrilucidi on
      airway remodeling in the asthmatic rats with the treatment of budesonide.
AB  - BACKGROUND: Asthma is characterized by chronic airway inflammation, leading to
      structura1 changes in the airway, collectively termed airway remodeling. Airway
      remodeling is thought to contribute to airway hyper responsiveness and
      irreversible airflow limitation. The combination of Herba Epimedii (HE) and
      Fructus Ligustri Lucidi (FLL) decoction and the systemic administration of
      glucocorticoids (GC) had a synergistic inhibitory action on airway inflammation
      in the asthmatic model rats. However, the effects of the combination on airway
      remodeling have not been studied and compared. In the present study, we
      investigated the effects of the co-administration of combined extracts of HE and
      FLL with inhaled GC (budesonide) on airway remodeling in the rat asthmatic model
      induced by ovalbumin (OVA). METHODS: Male Sprague-Dawley rats were sensitized to
      intraperitoneal OVA followed by repetitive OVA challenge for 7 weeks. Treatments
      included extracts of HE and FLL (Extracts for short, 100 mg/kg by gastric
      perfusion), budesonide (1 mg budesonide suspension in 50 ml sterile physiological
      saline, 3 rats in an ultrasonic nebulizer by nebulized inhabation with a flow of
      1.6 ml/min for 30 min), and co-administration of extracts of HE and FLL with
      budesonide (Co-administration for short) for 4 weeks. Lung histomorphometry and
      bronchoalveolar lavage fluid (BALF) cell count were assessed 24 h after the final
      OVA challenge. Levels of interleukin (IL)-4, IL-5 and IgE were measured by ELISA.
      Expressions of Collagen I and Collagen III were tested by immunohistology.
      Expressions of transforming growth factor (TGF) -beta1, TGF-beta2 and Smads mRNA
      were measured by quantitative real-time PCR. RESULTS: Extracts, budesonide and Co
      administration significantly reduced allergen-induced increases in the serum
      levels of IL-4, IL-5 and IgE, the number of eosinophils in BALF, goblet cell
      hyperplasia, Collagen III integral optical density (IOD) and the mRNA expression
      of TGF-beta2 and Smad2. Extracts and Co-administration could depress the IOD
      level of Collagen I and the positive area of Collagen I and Collagen III.
      Budesonide and Co-administration significantly alleviated the thickening of
      airway wall. Only Co-administration significantly decreased collagen deposition
      according to the morphometry of Masson's-stained lung sections, the thickening of
      airway smooth muscle layer, the number of lymphocytes in BALF and the mRNA
      expression of TGF-beta1 and Smad3, and this was associated with a significant
      increase in levels of Smad7 mRNA. CONCLUSIONS: The findings suggested that the
      combination of budesonide and the herbal extracts had a better synergistic effect
      on airway remodeling in OVA-reduced asthma rats than the single use of
      budesonide.

PMID- 28764782
TI  - Pre- and post-testing counseling considerations for the provision of expanded
      carrier screening: exploration of European geneticists' views.
AB  - BACKGROUND: Carrier screening is generally performed with the aim of identifying
      healthy couples at risk of having a child affected with a monogenic disorder to
      provide them with reproductive options. Expanded carrier screening (ECS), which
      provides the opportunity for multiple conditions to be screened in one test,
      offers a more cost-effective and comprehensive option than screening for single
      disorders. However, implementation of ECS at a population level would have
      implications for genetic counseling practice. METHODS: We conducted semi
      structured interviews with sixteen European clinical and molecular geneticists
      with expertise in carrier screening to explore their views on the implementation
      of ECS in the clinical setting. RESULTS: Using inductive content analysis, we
      identified content categories relevant to the pre- and post-test settings.
      Participants believed ECS would ideally be targeted at couples before pregnancy.
      There was some disagreement regarding the acceptability of performing ECS in
      individuals, with several participants actively opposing individual-based
      screening. In addition, participants discussed the importance of ensuring
      informed and voluntary participation in ECS, recommending measures to minimize
      external pressure on prospective parents to undergo testing. A need for adequate
      counseling to foster informed, autonomous reproductive decision-making and
      provide support for couples found to be at risk was emphasized. CONCLUSIONS:
      Practical challenges in optimizing pre-test education and post-test counseling
      should not be underestimated and they should be carefully addressed before
      implementing ECS in the clinical setting.

PMID- 28764783
TI  - Preferences and motivation for weight loss among knee replacement patients:
      implications for a patient-centered weight loss intervention.
AB  - BACKGROUND: Most knee replacement patients are overweight/obese, yet are commonly
      excluded from evidence-based weight loss programs due to mobility limitations and
      barriers faced around the time of surgery. The purpose of this study was to
      identify knee replacement patient preferences for weight loss programs and
      qualitatively understand previous motives for weight loss attempts as well as
      strategies used to facilitate behavior changes. METHODS: Patients who were either
      scheduled to have knee replacement or had one recently completed within the last
      3 months were recruited to participate. Patients completed a brief weight loss
      program preference questionnaire assessing preferred components of a weight loss
      program (i.e. self-monitoring, educational topics, program duration). Qualitative
      interviews were completed to identify motives for and strategies used during past
      weight loss attempts. All interviews were transcribed, de-identified, and
      analyzed using constant comparative analysis. RESULTS: Twenty patients (11 pre
      operative and 9 post-operative) between 47 and 79 years completed the study (55%
      male, 90% White, and 85% with a BMI >=25 kg/m2). Patients reported a preference
      for a weight loss program that starts before surgery, is at least 6 months in
      duration, and focuses both on diet and exercise. The majority of patients
      preferred to have a telephone-based program and wanted to track diet and physical
      activity on a smartphone application. The most common motive for weight loss
      mentioned by patients related to physical appearance (including how clothing
      fit), followed by wanting to lose weight to improve knee symptoms or to prevent
      or delay knee replacement. Strategies that patients identified as helpful during
      weight loss attempts included joining a formal weight loss program, watching
      portion sizes, and self-monitoring their dietary intake, physical activity, or
      weight. CONCLUSIONS: This study provides a preliminary examination into the
      motives for weight loss, strategies utilized during past weight loss attempts,
      and preferences for future weight loss programs as described by knee replacement
      patients. These results will help guide the development and adaptation of future
      patient-centered weight loss programs as well as help clinicians recommend
      targeted weight programs based on the specific preferences of the knee
      replacement population.

PMID- 28764784
TI  - E-cadherin expression phenotypes associated with molecular subtypes in invasive
      non-lobular breast cancer: evidence from a retrospective study and meta-analysis.
AB  - BACKGROUND: This retrospective study and meta-analysis was designed to explore
      the relationship between E-cadherin (E-cad) expression and the molecular subtypes
      of invasive non-lobular breast cancer, especially in early-stage invasive ductal
      carcinoma (IDC). METHODS: A total of 156 post-operative cases of early-stage IDCs
      were retrospectively collected for the immunohistochemistry (IHC) detection of E
      cad expression. The association of E-cad expression with molecular subtypes of
      early-stage IDCs was analyzed. A literature search was conducted in March 2016 to
      retrieve publications on E-cad expression in association with molecular subtypes
      of invasive non-lobular breast cancer, and a meta-analysis was performed to
      estimate the relational statistics. RESULTS: E-cad was expressed in 82.7%
      (129/156) of early-stage IDCs. E-cad expression was closely associated with the
      molecular types of early-stage IDCs (P < 0.050); moreover, the molecular subtypes
      were an independent factor influencing E-cad expression in early-stage IDCs. A
      total of 12 observational studies (including our study) were included in the meta
      analysis. The meta-analytical results show a significantly greater risk of E-cad
      expression loss in triple-negative breast cancer (TNBC) than in other molecular
      subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79-4.26; TNBC vs. luminal B:
      RR = 2.41, 95% CI = 1.49-3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24
      3.07). CONCLUSIONS: Early-stage IDCs or invasive non-lobular breast cancers with
      the TNBC molecular phenotype have a higher risk for the loss of E-cad expression
      than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad
      expression phenotypes were closely related to molecular subtypes and further
      studies are needed to clarify the underlying mechanism.

PMID- 28764785
TI  - Pathways for scaling up public health interventions.
AB  - BACKGROUND: To achieve population-wide health improvement, public health
      interventions found effective in selected samples need to be 'scaled up' and
      implemented more widely. The pathways through which interventions are scaled up
      are not well characterised. The aim of this paper is to identify examples of
      public health interventions which have been scaled up and to develop a conceptual
      framework which quantifies and describes this process. METHODS: A multi-stage
      international literature search was undertaken to identify examples of public
      health interventions in high income countries that have been scaled up or
      implemented at scale. Initial abstract review identified articles which met all
      the criteria of being a: 1) public health intervention; 2) chronic disease
      prevention focus; 3) program delivered at a wide geographical scale (state,
      national or international). Interventions were reviewed and coded into a
      conceptual framework pathway to document their scaling up process. For each
      program, an in-depth review of the identified articles was undertaken along with
      a broad internet based search to determine the outcomes of the dissemination
      process. A conceptual framework of scaling up pathways was developed that
      involved four stages (development, efficacy testing, real world trial and
      dissemination) to which the 40 programs were mapped. RESULTS: The search
      identified 40 public health interventions that showed evidence of being scaled
      up. Four pathways were identified to capture the different scaling up
      trajectories taken which included: 'Type I - Comprehensive' (55%) which passed
      through all four stages, 'Type II - Efficacy omitters' (5%) which did not conduct
      efficacy testing, 'Type III - Trial omitters' (25%) which did not conduct a real
      world trial, and 'Type IV - At scale dissemination' (15%) which skipped both
      efficacy testing and a real world trial. CONCLUSIONS: This is the first study to
      classify and quantify the potential pathways through which public health
      interventions in high income countries are scaled up to reach the broader
      population. Mapping these pathways not only demonstrates the different
      trajectories that occur in scaling up public health interventions, but also
      allows the variation across scaling up pathways to be classified. The policy and
      practice determinants leading to each pathway remain for future study, especially
      to identify the conditions under which efficacy and replication stages are
      missing.

PMID- 28764786
TI  - Evaluation of the antibacterial power and biocompatibility of zinc oxide nanorods
      decorated graphene nanoplatelets: new perspectives for antibiodeteriorative
      approaches.
AB  - BACKGROUND: Nanotechnologies are currently revolutionizing the world around us,
      improving the quality of our lives thanks to a multitude of applications in
      several areas including the environmental preservation, with the biodeterioration
      phenomenon representing one of the major concerns. RESULTS: In this study, an
      innovative nanomaterial consisting of graphene nanoplatelets decorated by zinc
      oxide nanorods (ZNGs) was tested for the ability to inhibit two different
      pathogens belonging to bacterial genera frequently associated with nosocomial
      infections as well as biodeterioration phenomenon: the Gram-positive
      Staphylococcus aureus and the Gram-negative Pseudomonas aeruginosa. A time- and
      dose-dependent bactericidal effect in cell viability was highlighted against both
      bacteria, demonstrating a strong antimicrobial potential of ZNGs. Furthermore,
      the analysis of bacterial surfaces through Field emission scanning electron
      microscopy (FESEM) revealed ZNGs mechanical interaction at cell wall level. ZNGs
      induced in those bacteria deep physical damages not compatible with life as a
      result of nanoneedle-like action of this nanomaterial together with its nanoblade
      effect. Cell injuries were confirmed by Fourier transform infrared spectroscopy,
      revealing that ZNGs antimicrobial effect was related to protein and phospholipid
      changes as well as a decrease in extracellular polymeric substances; this was
      also supported by a reduction in biofilm formation of both bacteria. The
      antibacterial properties of ZNGs applied on building-related materials make them
      a promising tool for the conservation of indoor/outdoor surfaces. Finally, ZNGs
      nanotoxicity was assessed in vivo by exploiting the soil free living nematode
      Caenorhabditis elegans. Notably, no harmful effects of ZNGs on larval
      development, lifespan, fertility as well as neuromuscular functionality were
      highlighted in this excellent model for environmental nanotoxicology.
      CONCLUSIONS: Overall, ZNGs represent a promising candidate for developing
      biocompatible materials that can be exploitable in antimicrobial applications
      without releasing toxic compounds, harmful to the environment.

PMID- 28764787
TI  - Assessing the capacity of ministries of health to use research in decision
      making: conceptual framework and tool.
AB  - BACKGROUND: The capacity to demand and use research is critical for governments
      if they are to develop policies that are informed by evidence. Existing tools
      designed to assess how government officials use evidence in decision-making have
      significant limitations for low- and middle-income countries (LMICs); they are
      rarely tested in LMICs and focus only on individual capacity. This paper
      introduces an instrument that was developed to assess Ministry of Health (MoH)
      capacity to demand and use research evidence for decision-making, which was
      tested for reliability and validity in eight LMICs (Bangladesh, Fiji, India,
      Lebanon, Moldova, Pakistan, South Africa, Zambia). METHODS: Instrument
      development was based on a new conceptual framework that addresses individual,
      organisational and systems capacities, and items were drawn from existing
      instruments and a literature review. After initial item development and pre
      testing to address face validity and item phrasing, the instrument was reduced to
      54 items for further validation and item reduction. In-country study teams
      interviewed a systematic sample of 203 MoH officials. Exploratory factor analysis
      was used in addition to standard reliability and validity measures to further
      assess the items. RESULTS: Thirty items divided between two factors representing
      organisational and individual capacity constructs were identified. South Africa
      and Zambia demonstrated the highest level of organisational capacity to use
      research, whereas Pakistan and Bangladesh were the lowest two. In contrast,
      individual capacity was highest in Pakistan, followed by South Africa, whereas
      Bangladesh and Lebanon were the lowest. CONCLUSION: The framework and related
      instrument represent a new opportunity for MoHs to identify ways to understand
      and improve capacities to incorporate research evidence in decision-making, as
      well as to provide a basis for tracking change.

PMID- 28764788
TI  - Regulation of human glioma cell apoptosis and invasion by miR-152-3p through
      targeting DNMT1 and regulating NF2 : MiR-152-3p regulate glioma cell apoptosis
      and invasion.
AB  - BACKGROUND: MiRNAs are involved in aberrant DNA methylation through regulation of
      DNA methyltransferases (DNMTs) in the pathogenesis and progression of
      glioblastomas (GBM). MiR-152-3p was down-expressed in human malignancies, and
      served as a tumor suppressor. Neurofibromatosis type 2 (NF2) was significantly
      decreased in GBM tissues with a high level of methylation. However, the link
      between miR-152-3p, DNMT1 and methylation of NF2 in GBM is not clearly
      established. This study was conducted to detect the mechanism between miR-152-3p,
      DNMT1 and NF2 in GBM. METHODS: The levels of DNMT1 and NF2 expression were
      studied by qRT-PCR, Western blot, immunofluorescence, and immumohistochemical
      staining. Methylation in the promoter region of NF2 was detected by methylation
      specific PCR and bisulfate genomic sequencing PCR. Cell proliferation was
      examined by Cell-Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assay, and cell
      invasion was evaluated by transwell assay. Flow cytomery and Hoechst staining
      were used to analyze cell apoptosis. A dual luciferase system was used to confirm
      the relationship between miR-152-3p and DNMT1. RESULTS: Methylation of NF2 and
      DNMT1 was markedly increased, and miR-152-3p was downregulated in GBM tissues and
      glioma cells. Both knockdown of DNMT1 and overexpression miR-152-3p showed that
      demethylation activated the expression of NF2. Furthermore, miR-152-3p directly
      targeted DNMT1. Both miR-152-3p overexpression and DNMT1 knockdown significantly
      induced cell apoptosis and inhibited invasive activity. This was also observed
      after NF2 overexpression. CONCLUSIONS: These results indicated that miR-152-3p
      can inhibit glioma cell proliferation and invasion activities by decreasing
      DNMT1. The restoration of miR-152-3p may have therapeutic application in the
      treatment of GBM.

PMID- 28764789
TI  - Exploring how nurses assess, monitor and manage acute pain for adult critically
      ill patients in the emergency department: protocol for a mixed methods study.
AB  - BACKGROUND: Many critically ill patients experience moderate to severe acute pain
      that is frequently undetected and/or undertreated. Acute pain in this patient
      cohort not only derives from their injury and/or illness, but also as a
      consequence of delivering care whilst stabilising the patient. Emergency nurses
      are increasingly responsible for the safety and wellbeing of critically ill
      patients, which includes assessing, monitoring and managing acute pain. How
      emergency nurses manage acute pain in critically ill adult patients is unknown.
      The objective of this study is to explore how emergency nurses manage  acute pain
      in critically ill patients in the Emergency Department. METHODS: In this paper,
      we provide a detailed description of the methods and protocol for a multiphase
      sequential mixed methods study, exploring how emergency nurses assess, monitor
      and manage acute pain in critically ill adult patients. The objective, method,
      data collection and analysis of each phase are explained. Justification of each
      method and data integration is described. DISCUSSION: Synthesis of findings will
      generate a comprehensive picture of how emergency nurses' perceive and manage
      acute pain in critically ill adult patients. The results of this study will form
      a knowledge base to expand theory and inform research and practice.

PMID- 28764790
TI  - Successful management of rare gingival metastasis from gastric adenocarcinoma: a
      case report and literature review.
AB  - BACKGROUND: Gastric cancer rarely metastasizes to the oral cavity, especially to
      gingiva. Only 18 cases have been reported worldwide to date. This paper herein
      presents the nineteenth case of gingival metastasis from gastric cancer. CASE
      PRESENTATION: A 75-year-old man who underwent a radical gastrectomy for gastric
      adenocarcinoma was admitted to clinical oncology center for gingival mass which
      was originally diagnosed as epulis. The subsequent positron emission tomography
      computed tomography (PET-CT) and histopathological examination revealed a
      gingival metastatic adenocarcinoma originated from gastric carcinoma. Then three
      dimensional conformal radiotherapy (3D-CRT) with synchronization and sequential
      chemotherapy demonstrated clinical benefit in this patient. Furthermore, this
      research reviewed the records of 18 cases of gingival metastasis from gastric
      carcinoma in English, Japanese, and Chinese literature, and summarized the
      clinicopathologic features of the disease based on previously published papers.
      CONCLUSION: This case suggests that gingival metastasis from gastric cancer is
      worthy of vigilance. Biopsy and immunohistochemical (IHC) staining should be used
      for the final diagnosis. Moreover, the patient with uncommon gingival metastatic
      lesion can be successfully treated by radiotherapy with adjuvant chemotherapy.

PMID- 28764791
TI  - Metachronous colorectal carcinoma with massive submucosal invasion detected by
      annual surveillance in a Lynch syndrome patient: a case report.
AB  - BACKGROUND: Lynch syndrome is the most common form of hereditary colorectal
      carcinoma. It is characterized by the presence of germline mutations in DNA
      mismatch repair genes. Mutation carriers have a lifetime risk of developing
      colorectal carcinoma of approximately 80%. Current treatment guidelines recommend
      periodic surveillance for colorectal carcinoma in patients with Lynch syndrome.
      However, the optimal interval between colonoscopies has not yet been determined.
      CASE PRESENTATION: We describe a 54-year-old man with Lynch syndrome who was
      undergoing annual colonoscopy surveillance for the development of colorectal
      carcinoma. At 54, 57, 59, and 60 years old, a colonoscopy showed high-grade
      dysplasia and adenoma. Therefore, endoscopic mucosal resection was performed. At
      61 years old, a colonoscopy showed metachronous colorectal carcinoma with massive
      submucosal invasion. He subsequently underwent laparotomy for colorectal
      carcinoma. CONCLUSIONS: Annual surveillance using colonoscopy can detect
      colorectal carcinoma at an early stage, leading to reduced mortality. However,
      some patients might require a laparotomy, as was the case here. More frequent
      colonoscopic surveillance might be necessary to avoid surgery for colorectal
      carcinoma in Lynch syndrome patients with multiple risk factors for interval
      cancer.

PMID- 28764792
TI  - Deployment and use of mobile phone technology for real-time reporting of fever
      cases and malaria treatment failure in areas of declining malaria transmission in
      Muheza district north-eastern Tanzania.
AB  - BACKGROUND: Early detection of febrile illnesses at community level is essential
      for improved malaria case management and control. Currently, mobile phone-based
      technology has been commonly used to collect and transfer health information and
      services in different settings. This study assessed the applicability of mobile
      phone-based technology in real-time reporting of fever cases and management of
      malaria by village health workers (VHWs) in north-eastern Tanzania. METHODS: The
      community mobile phone-based disease surveillance and treatment for malaria
      (ComDSTM) platform, combined with mobile phones and web applications, was
      developed and implemented in three villages and one dispensary in Muheza district
      from November 2013 to October 2014. A baseline census was conducted in May 2013.
      The data were uploaded on a web-based database and updated during follow-up home
      visits by VHWs. Active and passive case detection (ACD, PCD) of febrile cases
      were done by VHWs and cases found positive by malaria rapid diagnostic test (RDT)
      were given the first dose of artemether-lumefantrine (AL) at the dispensary. Each
      patient was visited at home by VHWs daily for the first 3 days to supervise
      intake of anti-malarial and on day 7 to monitor the recovery process. The data
      were captured and transmitted to the database using mobile phones. RESULTS: The
      baseline population in the three villages was 2934 in 678 households. A total of
      1907 febrile cases were recorded by VHWs and 1828 (95.9%) were captured using
      mobile phones. At the dispensary, 1778 (93.2%) febrile cases were registered and
      of these, 84.2% were captured through PCD. Positivity rates were 48.2 and 45.8%
      by RDT and microscopy, respectively. Nine cases had treatment failure reported on
      day 7 post-treatment and adherence to treatment was 98%. One patient with severe
      febrile illness was referred to Muheza district hospital. CONCLUSION: The study
      showed that mobile phone-based technology can be successfully used by VHWs in
      surveillance and timely reporting of fever episodes and monitoring of treatment
      failure in remote areas. Further optimization and scaling-up will be required to
      utilize the tools for improved malaria case management and drug resistance
      surveillance.

PMID- 28764793
TI  - Plasma concentrations of caspofungin in a critically ill patient with morbid
      obesity.

PMID- 28764794
TI  - Exploration of knowledge and understanding in patients with primary adrenal
      insufficiency: a mixed methods study.
AB  - BACKGROUND: Primary adrenal insufficiency (PAI) is a rare and severe condition
      requiring lifelong steroid replacement. During acute illness or stressful events,
      it is important to appropriately adjust glucocorticoid dose; failure to do so may
      lead to an adrenal crisis. The aim of the study was to explore patients PAI
      knowledge and understanding of the condition, steroid replacement adjustment
      during acute illness or stress and provided education. METHODS: Ten adult
      patients with PAI were purposefully recruited from two hospitals in a tertiary
      NHS Trust in England, UK. Data was collected using a mixed method approach
      utilising semi-structured audio-recorded interviews and hospital case note
      review. Interviews were transcribed verbatim and analysed using Burnard's content
      analysis framework. Information from the hospital case note review was captured
      using a matrix table based on pre-defined criteria. RESULTS: Four key themes
      emerged: 'Addison's disease and hydrocortisone replacement'; 'stress and
      corticosteroids'; 'patient compliance/adherence' and 'transition'. Patients
      reported feelings of 'going through a transition from uncertainty to adaption'
      following diagnosis. All participants had a good level of knowledge and
      understanding of required medication however application in times of need was
      poor. Medication adherence and prevention of a crisis relied not only on patient
      knowledge and application but also the support of family and health
      professionals. Health care professional knowledge required improvement to aid
      diagnosis and management of PAI. CONCLUSION: Patients with PAI did not apply
      existing knowledge to adjust steroid dose during acute illness or stress.
      Although a sample of limited size, our study identified there is a need to
      further explore why patients with Addison's disease do not apply existing
      knowledge during times of increased need. Future research should consider
      appropriate behaviour change interventions to promote medication adherence to
      reduce risk of an adrenal crisis.

PMID- 28764795
TI  - Participation of 14-3-3epsilon and 14-3-3zeta proteins in the phagocytosis,
      component of cellular immune response, in Aedes mosquito cell lines.
AB  - BACKGROUND: Better knowledge of the innate immune system of insects will improve
      our understanding of mosquitoes as potential vectors of diverse pathogens. The
      ubiquitously expressed 14-3-3 protein family is evolutionarily conserved from
      yeast to mammals, and at least two isoforms of 14-3-3, the epsilon and zeta, have
      been identified in insects. These proteins have been shown to participate in both
      humoral and cellular immune responses in Drosophila. As mosquitoes of the genus
      Aedes are the primary vectors for arboviruses, causing several diseases such as
      dengue fever, yellow fever, Zika and chikungunya fevers, cell lines derived from
      these mosquitoes, Aag-2 from Aedes aegypti and C6/36 HT from Aedes albopictus,
      are currently used to study the insect immune system. Here, we investigated the
      role of 14-3-3 proteins (epsilon and zeta isoform) in phagocytosis, the main
      cellular immune responses executed by the insects, using Aedes spp. cell lines.
      RESULTS: We evaluated the mRNA and protein expression of 14-3-3epsilon and 14-3
      3zeta in C6/36 HT and Aag-2 cells, and demonstrated that both proteins were
      localised in the cytoplasm. Further, in C6/36 HT cells treated with a 14-3-3
      specific inhibitor we observed a notable modification of cell morphology with
      filopodia-like structure caused through cytoskeleton reorganisation (co
      localization of 14-3-3 proteins with F-actin), more importantly the decrease in
      Salmonella typhimurium, Staphylococcus aureus and E. coli phagocytosis and
      reduction in phagolysosome formation. Additionally, silencing of 14-3-3epsilon
      and 14-3-3zeta expression by mean of specific DsiRNA confirmed the decreased
      phagocytosis and phagolysosome formation of pHrodo labelled E. coli and S. aureus
      bacteria by Aag-2 cells. CONCLUSION: The 14-3-3epsilon and 14-3-3zeta proteins
      modulate cytoskeletal remodelling, and are essential for phagocytosis of Gram
      positive and Gram-negative bacteria in Aedes spp. cell lines.

PMID- 28764796
TI  - Anticholinergic drugs and functional, cognitive impairment and behavioral
      disturbances in patients from a memory clinic with subjective cognitive decline
      or neurocognitive disorders.
AB  - BACKGROUND: Drugs with anticholinergic properties may be associated with various
      adverse clinical effects. The relationship between the anticholinergic (AC)
      burden and functional, global cognitive performance and behavior disturbances was
      assessed among elderly patients. METHODS: A cross-sectional study was conducted
      between January 2012 and June 2014 in a memory clinic among outpatients living at
      home and with subjective cognitive decline (SCD) or neurocognitive disorders
      (NCD). The AC burden was measured using the Anticholinergic Drug Scale (ADS), the
      Anticholinergic Risk Scale (ARS), the Anticholinergic Cognitive Burden (ACB),
      Chew's score, Han's score, and the number of drugs with AC activity. Functional,
      cognitive performance and behavior disturbances were assessed using the
      Instrumental Activities of Daily Living (IADL) scale (IADL), the Mini Mental
      State Examination (MMSE), and the Neuropsychiatric Inventory (NPI). RESULTS:
      Among 473 included patients, 46.3% were at major NCD. Patients took on average
      5.3 +/- 2.6 drugs. MMSE was lower when Han's score (p = 0.04) and number of AC
      drugs were higher (p < 0.001). IADL was lower when AC burden was higher, whatever
      the AC measurement. NPI was higher when ACB, Han's score, and number of AC drugs
      were higher. After adjustment, all AC scores remained associated with IADL, while
      Han's score and number of drugs with AC remained associated with the MMSE.
      CONCLUSIONS: In patients with SCD or NCD, AC burden is associated with lower
      functional score, whereas the cross-sectional association between AC burden and
      cognitive performance or behavioral disturbance varies according to AC scores.
      Particular attention should be paid when prescribing drugs with AC properties,
      especially among patients with memory complaints.

PMID- 28764797
TI  - Conventional osteosarcoma of the mandible successfully treated with radical
      surgery and adjuvant chemotherapy after responding poorly to neoadjuvant
      chemotherapy: a case report.
AB  - BACKGROUND: Osteosarcoma, the most common primary bone malignancy, has an
      extremely poor prognosis and a high rate of local recurrence and distal
      metastases. Because osteosarcomas of the head and neck region are rare,
      accounting for less than 10% of all osteosarcoma cases, limited information is
      available about their treatment and prognosis. Because of the high rate of distal
      metastases associated with extragnathic osteosarcoma, surgery combined with
      chemotherapy is currently considered essential in its treatment. However, the
      role of chemotherapy has not been well elucidated in the treatment of head and
      neck osteosarcoma because of the rarity of this condition. CASE PRESENTATION: In
      this report, we present the case of a 58-year-old Japanese woman with
      osteosarcoma of the mandible that was treated with radical surgery combined with
      neoadjuvant and adjuvant chemotherapy. Because the tumor showed rapid growth
      during neoadjuvant chemotherapy, neoadjuvant chemotherapy was suspended and
      surgical resection was performed, followed by adjuvant chemotherapy. No evidence
      of local recurrence and distal metastasis was found 14 months after initial
      treatment. Local control is considered a principal prognostic factor for head and
      neck osteosarcoma. CONCLUSIONS: Wide surgical excision should be considered a
      primary goal even during neoadjuvant chemotherapy, especially in cases that
      respond poorly to neoadjuvant chemotherapy.

PMID- 28764799
TI  - Metabolomics study of the therapeutic mechanism of Schisandra Chinensis lignans
      in diet-induced hyperlipidemia mice.
AB  - BACKGROUND: Schisandra, a globally distributed plant, has been widely applied for
      the treatment of diseases such as hyperlipidemia, fatty liver and obesity in
      China. In the present work, a rapid resolution liquid chromatography coupled with
      quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS)-based metabolomics was
      conducted to investigate the intervention effect of Schisandra chinensis lignans
      (SCL) on hyperlipidemia mice induced by high-fat diet (HFD). METHODS:
      Hyperlipidemia mice were orally administered with SCL (100 mg/kg) once a day for
      4 weeks. Serum biochemistry assay of triglyceride (TG), total cholesterol (TC),
      low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein
      cholesterol (HDL-c) was conducted to confirm the treatment of SCL on lipid
      regulation. Metabolomics analysis on serum samples was carried out, and principal
      component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA)
      were carried out for the pattern recognition and characteristic metabolites
      identification. The relative levels of critical regulatory factors of liver lipid
      metabolism, sterol regulatory element-binding proteins (SREBPs) and its related
      gene expressions were measured by quantitative real-time polymerase chain
      reaction (RT-PCR) for investigating the underlying mechanism. RESULTS: Oral
      administration of SCL significantly decreased the serum levels of TC, TG and LDL
      c and increased the serum level of HDL-c in the hyperlipidemia mice, and no
      effect of SCL on blood lipid levels was observed in control mice. Serum samples
      were scattered in the PCA scores plots in response to the control, HFD and SCL
      group. Totally, thirteen biomarkers were identified and nine of them were
      recovered to the normal levels after SCL treatment. Based on the Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathways analysis, the anti
      hyperlipidemia mechanisms of SCL may be involved in the following metabolic
      pathways: tricarboxylic acid (TCA) cycle, synthesis of ketone body and
      cholesterol, choline metabolism and fatty acid metabolism. Meanwhile, SCL
      significantly inhibited the mRNA expression level of hepatic lipogenesis genes
      such as SREBP-1c, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), and
      decreased the mRNA expression of liver X receptor alpha (LXRalpha). Moreover, SCL
      also significantly decreased the expression level of SREBP-2 and 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMGCR) in the liver of hyperlipidemia mice.
      CONCLUSION: Anti-hyperlipidemia effect of SCL was confirmed by both serum
      biochemistry and metabolomics analysis. The mechanism may be related to the down
      regulation of LXRalpha/SREBP-1c/FAS/ACC and SREBP2/HMGCR signaling pathways.

PMID- 28764800
TI  - 'We knew it was a totally at random thing': parents' experiences of being part of
      a neonatal trial.
AB  - BACKGROUND: Studies exploring parents' trial experiences generally relate to
      their understanding of the consent process and the development of researcher
      strategies to facilitate recruitment and retention. The aim was to better
      understand parents' experience of being part of a trial at the time and their
      perceptions of trial participation in retrospect. METHODS: Data were collected in
      a number of ways: from recorded discussions between parents and clinicians about
      the MRI or ultrasound, in open-text responses to questionnaires and in
      qualitative interviews at 1 and 2 years after participation. Thematic analysis
      was undertaken using NVivo10. RESULTS: Key themes identified were 'deciding to
      take part', with subthemes associated with 'benefitting self', 'benefitting
      others' and 'being prepared'; 'the randomisation process' with subthemes relating
      to 'acceptance' and 'understanding' and 'actual engagement' with subthemes of
      'practicalities' and 'care from responsive staff'. CONCLUSION: Parents'
      perspectives on the trial and the processes and information received reflect
      their understanding and experience of the trial and the value of parent-friendly
      information-giving about participation, randomisation and follow-up. The
      practical and logistical points raised confirm the key issues and parents' need
      for sensitive care and support in the course of a trial. Looking back, almost all
      parents were positive about their experience and felt that the family had
      benefitted from participation in the trial and follow-up studies, even when the
      developmental outcomes were poor. TRIAL REGISTRATION: ClinicalTrials.gov, ID:
      NCT01049594. https://clinicaltrials.gov/ct2/show/NCT01049594 . Registered on 13
      January 2010. EudraCT: EudraCT: 2009-011602-42.
      https://www.clinicaltrialsregister.eu/ .

PMID- 28764798
TI  - An interaction map of circulating metabolites, immune gene networks, and their
      genetic regulation.
AB  - BACKGROUND: Immunometabolism plays a central role in many cardiometabolic
      diseases. However, a robust map of immune-related gene networks in circulating
      human cells, their interactions with metabolites, and their genetic control is
      still lacking. Here, we integrate blood transcriptomic, metabolomic, and genomic
      profiles from two population-based cohorts (total N = 2168), including a subset
      of individuals with matched multi-omic data at 7-year follow-up. RESULTS: We
      identify topologically replicable gene networks enriched for diverse immune
      functions including cytotoxicity, viral response, B cell, platelet, neutrophil,
      and mast cell/basophil activity. These immune gene modules show complex patterns
      of association with 158 circulating metabolites, including lipoprotein
      subclasses, lipids, fatty acids, amino acids, small molecules, and CRP. Genome
      wide scans for module expression quantitative trait loci (mQTLs) reveal five
      modules with mQTLs that have both cis and trans effects. The strongest mQTL is in
      ARHGEF3 (rs1354034) and affects a module enriched for platelet function,
      independent of platelet counts. Modules of mast cell/basophil and neutrophil
      function show temporally stable metabolite associations over 7-year follow-up,
      providing evidence that these modules and their constituent gene products may
      play central roles in metabolic inflammation. Furthermore, the strongest mQTL in
      ARHGEF3 also displays clear temporal stability, supporting widespread trans
      effects at this locus. CONCLUSIONS: This study provides a detailed map of natural
      variation at the blood immunometabolic interface and its genetic basis, and may
      facilitate subsequent studies to explain inter-individual variation in
      cardiometabolic disease.

PMID- 28764801
TI  - Hemodialysis in MNGIE transiently reduces serum and urine levels of thymidine and
      deoxyuridine, but not CSF levels and neurological function.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare,
      autosomal-recessive mitochondrial disorder caused by TYMP mutations presenting
      with a multisystemic, often lethal syndrome of progressive leukoencephalopathy,
      ophthalmoparesis, demyelinating neuropathy, cachexia and gastrointestinal
      dysmotility. Hemodialysis (HMD) has been suggested as a treatment to reduce
      accumulation of thymidine and deoxyuridine. However, all studies so far have
      failed to measure the toxic metabolites in cerebrospinal fluid (CSF), which is
      the crucial compartment for CNS damage.Our study is the first prospective,
      longitudinal investigation, exploiting detailed serial testing of predefined
      clinical and molecular outcome parameters (including serial CSF assessments) in a
      29-year-old MNGIE patient undergoing 1 year of extensive HMD. We demonstrate that
      HMD only transiently restores increased serum and urine levels of thymidine and
      deoxyuridine, but fails to reduce CSF levels of the toxic metabolites and is
      ineffective to influence neurological function. These findings have direct
      important implications for clinical practice: They prevent a burdensome, long
      term invasive, but ultimately probably ineffective procedure in future MNGIE
      patients.

PMID- 28764802
TI  - Mesenchymal stem cells derived from inflamed dental pulpal and gingival tissue: a
      potential application for bone formation.
AB  - BACKGROUND: Chronic periodontal disease is an infectious disease consisting of
      prolonged inflammation of the supporting tooth tissue and resulting in bone loss.
      Guided bone regeneration procedures have become common and safe treatments in
      dentistry, and in this context dental stem cells would represent the ideal
      solution as autologous cells. In this study, we verified the ability of dental
      pulp mesenchymal stem cells (DPSCs) and gingival mesenchymal stem cells (GMSCs)
      harvested from periodontally affected teeth to produce new mineralized bone
      tissue in vitro, and compared this to cells from healthy teeth. METHODS: To
      characterize DPSCs and GMSCs, we assessed colony-forming assay,
      immunophenotyping, mesenchymal/stem cell phenotyping, stem gene profiling by
      means of flow cytometry, and quantitative polymerase chain reaction (qPCR). The
      effects of proinflammatory cytokines on mesenchymal stem cell (MSC) proliferation
      and differentiation potential were investigated. We also observed participation
      of several heat shock proteins (HSPs) and actin-depolymerizing factors (ADFs)
      during osteogenic differentiation. RESULTS: DPSCs and GMSCs were successfully
      isolated both from periodontally affected dental tissue and controls.
      Periodontally affected dental MSCs proliferated faster, and the inflamed
      environment did not affect MSC marker expressions. The calcium deposition was
      higher in periodontally affected MSCs than in the control group. Proinflammatory
      cytokines activate a cytoskeleton remodeling, interacting with HSPs including
      HSP90 and HSPA9, thioredoxin-1, and ADFs such as as profilin-1, cofilin-1, and
      vinculin that probably mediate the increased acquisition in the inflamed
      environment. CONCLUSIONS: Our findings provide evidence that periodontally
      affected dental tissue (both pulp and gingiva) can be used as a source of MSCs
      with intact stem cell properties. Moreover, we demonstrated that the osteogenic
      capability of DPSCs and GMSCs in the test group was not only preserved but
      increased by the overexpression of several proinflammatory cytokine-dependent
      chaperones and stress response proteins.

PMID- 28764803
TI  - A novel RLBP1 gene geographical area-related mutation present in a young patient
      with retinitis punctata albescens.
AB  - BACKGROUND: Autosomal recessive forms of retinitis punctata albescens (RPA) have
      been described. RPA is characterized by progressive retinal degeneration due to
      alteration in visual cycle and consequent deposit of photopigments in retinal
      pigment epithelium. Five loci have been linked to RPA onset. Among these, the
      retinaldehyde-binding protein 1 gene, RLBP1, is the most frequently involved and
      several founder mutations were reported. We report results of a genetic molecular
      investigation performed on a large Sicilian family in which appears a young woman
      with RPA. RESULTS: The proband is in homozygous condition for a novel RLBP1
      single-pair deletion, and her healthy parents, both heterozygous, are not
      consanguineous. Thenovelc.398delC (p.P133Qfs*258) involves the exon 6 and leads
      to a premature stop codon, resulting in a truncated protein entirely missing of
      CRAL-TRIO lipid-binding domain. Pedigree analysis showed other non-consanguineous
      relatives heterozygous for the same mutation in the family. Extension of mutation
      research in the native town of the proband revealed its presence also in healthy
      subjects, in a heterozygous condition. CONCLUSIONS: A novel RLBP1 truncating
      mutation was detected in a young girl affected by RPA. Although her parents are
      not consanguineous, the mutation was observed in a homozygous condition. Being
      them native of the same small Sicilian town of Fiumedinisi, the hypothesis of a
      geographical area-related mutation was assessed and confirmed.

PMID- 28764804
TI  - Effects of date palm pollen on fertility: research proposal for a systematic
      review.
AB  - OBJECTIVE: Over 10-15% of couples in different countries are infertile. Male
      infertility is a contributing factor and the only cause of infertility in
      respectively 50% and 20-30% of all cases of infertility. According to previous
      research, micro-elements isolated from date palm pollen (DPP), e.g. estrogen and
      sterols, may enhance male and female fertility. DPP has also been reported to
      improve sperm parameters including sperm motility and viability, acrosome
      reaction, and lipid peroxidation. This article may justify the need for a future
      systematic review and meta-analysis about the effects of DPP on the reproductive
      system and DPP's ability to enhance fertility. It will then describe the
      methodology of such a study. MAIN TEXT: A comprehensive search of relevant
      randomized and quasi-randomized controlled trials will be performed in MEDLINE,
      EMBASE, Web of Science, Cochrane Central, ProQuest, and Google Scholar databases.
      Two authors will independently assess the eligibility of the studies and consult
      the third author in cases of disagreement. The risk of bias of the randomized
      controlled trials and animal studies will be evaluated using the Cochrane risk of
      bias tool and the Systematic Review Centre for Laboratory animal Experimentation
      (SYRCLE) risk of bias tool, respectively. This study will raise no ethical issues
      as it will review the findings of previous research. The results are intended to
      be published in a peer-reviewed medical journal.

PMID- 28764805
TI  - Confounding variables impacting the association between duration of veno-arterial
      extracorporeal life support and mortality.

PMID- 28764806
TI  - The relationship of primary care providers to dental practitioners in rural and
      remote Australia.
AB  - BACKGROUND: Rural residents have poorer oral health and more limited access to
      dental services than their city counterparts. In rural communities, health care
      professionals often work in an extended capacity due to the needs of the
      community and health workforce shortages in these areas. Improved links and
      greater collaboration between resident rural primary care and dental
      practitioners could help improve oral health service provision such that
      interventions are both timely, effective and lead to appropriate follow-up and
      referral. This study examined the impact oral health problems had on primary
      health care providers; how primary care networks could be more effectively
      utilised to improve the provision of oral health services to rural communities;
      and identified strategies that could be implemented to improve oral health.
      METHODS: Case studies of 14 rural communities across three Australian states.
      Between 2013 and 2016, 105 primary and 12 dental care providers were recruited
      and interviewed. Qualitative data were analysed in Nvivo 10 using thematic
      analysis. Quantitative data were subject to descriptive analysis using SPSSv20.
      RESULTS: Rural residents presented to primary care providers with a range of oral
      health problems from "everyday" to "10 per month". Management by primary care
      providers commonly included short-term pain relief, antibiotics, and advice that
      the patient see a dentist. The communication between non-dental primary care
      providers and visiting or regional dental practitioners was limited. Participants
      described a range of strategies that could contribute to better oral health and
      oral health oral services in their communities. CONCLUSIONS: Rural oral health
      could be improved by building oral health capacity of non-dental care providers;
      investing in oral health promotion and prevention activities; introducing more
      flexible service delivery practices to meet the dental needs of both public and
      private patients; and establishing more effective communication and referral
      pathways between rural primary and visiting/regional dental care providers.

PMID- 28764807
TI  - AKT1low quiescent cancer cells persist after neoadjuvant chemotherapy in triple
      negative breast cancer.
AB  - BACKGROUND: Absence of pathologic complete response (pCR) to neoadjuvant
      chemotherapy (NACT) correlates with poor long-term survival in patients with
      triple negative breast cancer (TNBC). These incomplete treatment responses are
      likely determined by mechanisms that enable cancer cells to resist being killed.
      However, the detailed characterization of a drug-resistant cancer cell state in
      residual TNBC tissue after NACT has remained elusive. AKT1low quiescent cancer
      cells (QCCs) are a quiescent, epigenetically plastic, and chemotherapy-resistant
      subpopulation initially identified in experimental cancer models. Here, we asked
      whether QCCs exist in primary tumors from patients with TNBC and persist after
      treatment with NACT. METHODS: We obtained pre-treatment biopsy, post-treatment
      mastectomy, and metastatic specimens from a retrospective cohort of TNBC patients
      treated with NACT at Massachusetts General Hospital (n = 25). Using quantitative
      automated immunofluorescence microscopy, QCCs were identified as
      AKTlow/H3K9me2low/HES1high cancer cells using prespecified immunofluorescence
      intensity thresholds. QCCs were represented in 2D and 3D digital tumor maps and
      QCC percentage (QCC-P) and QCC cluster index (QCC-CI) were determined for each
      sample. RESULTS: We showed that QCCs exist as non-random and heterogeneously
      distributed clusters within primary breast tumors. In addition, these QCC
      clusters persist after treatment with multi-agent, multi-cycle, neoadjuvant
      chemotherapy in both residual primary tumors and nodal and distant metastases in
      patients with triple negative breast cancer. CONCLUSIONS: These first-in-human
      data potentially qualify AKT1low quiescent cancer cells as a non-genetic cell
      state that persists after neoadjuvant chemotherapy in triple negative breast
      cancer patients and warrants further study.

PMID- 28764808
TI  - Association between MPO-463G > A polymorphism and cancer risk: evidence from 60
      case-control studies.
AB  - BACKGROUND: Though a number of studies have been conducted to explore the
      association between myeloperoxidase (MPO)-463G > A polymorphism and cancer risk,
      the results remain inconsistent. Therefore, we performed a meta-analysis to
      derive a more systematic estimation of this relationship. METHOD: Relevant
      studies were searched by PubMed, EMBASE, CNKI, Google Scholar, Ovid, and Cochrane
      library prior to December 2015. The strength of the association between MPO-463G
      > A polymorphism and cancer risk was estimated by odds ratios (OR) with 95%
      confidence interval (95%CI). Cumulative analysis was used to evaluate the
      stability of results through time. RESULTS: The current analysis consisted of
      16,858 cases and 21,756 controls from 60 studies. Pooled results showed that MPO
      463G > A polymorphism were associated with the overall decreased cancer
      susceptibility in all the genetic models included in this study (additive model:
      OR = 0.84, 95%CI = 0.76-0.94; allele genetic model: OR = 0.90, 95%CI = 0.840
      0.954; recessive genetic model: OR = 0.89, 95%CI = 0.83-0.95). However, in the
      stratified analysis of cancer type, the significant results were only found in
      lung cancer (dominant model: OR = 0.93, 95%CI = 0.87-0.99) and digestive system
      cancer groups (dominant model: OR = 0.67 0.53-0.84; allele frequency model =
      0.71, 95%CI = 0.57-0.87), but not in the blood system cancer or breast cancer
      group. When we further stratified the digestive system cancer group into
      digestive tract and digestive gland cancer groups, results showed a significant
      association between allele A of MPO-463G > A and digestive gland cancer in all
      the genetic models (allele frequency model: OR = 0.63, 95%CI = 0.40-0.99;
      additive model: OR = 0.41, 95%CI = 0.23-0.73; recessive model: OR = 0.51, 95%CI =
      0.29-0.89; dominant model: OR = 0.58, 95%CI = 0.35-0.96), digestive tract cancers
      in allele frequency model (OR = 0.75, 95%CI = 0.59-0.95), and dominant model (OR
      = 0.72, 95%CI = 0.56-0.92). When stratified by ethnicity, results demonstrated
      that the genotype A might be a protect factor for both Caucasians and Asians. In
      group analysis according to source of controls, significant results were found in
      population from hospital in all the genetic models. In cumulative analysis,
      result of allele contrast showed a declining trend and increasingly narrower 95%
      overall, while the inclination toward non-significant association with lung
      cancer risk. CONCLUSIONS: This meta-analysis suggested that MPO-463G > A
      polymorphism was associated with the overall reduced cancer susceptibility
      significantly. It might be a more reliable predictor of digestive system cancer
      instead of lung cancer, blood system cancer, and breast cancer. In cumulative
      analysis, the stable trend indicated that evidence was sufficient to show the
      association between MPO-463G > A polymorphism and cancer risk.

PMID- 28764809
TI  - Barriers to the conduct of randomised clinical trials within all disease areas.
AB  - BACKGROUND: Randomised clinical trials are key to advancing medical knowledge and
      to enhancing patient care, but major barriers to their conduct exist. The present
      paper presents some of these barriers. METHODS: We performed systematic
      literature searches and internal European Clinical Research Infrastructure
      Network (ECRIN) communications during face-to-face meetings and telephone
      conferences from 2013 to 2017 within the context of the ECRIN Integrating
      Activity (ECRIN-IA) project. RESULTS: The following barriers to randomised
      clinical trials were identified: inadequate knowledge of clinical research and
      trial methodology; lack of funding; excessive monitoring; restrictive privacy law
      and lack of transparency; complex regulatory requirements; and inadequate
      infrastructures. There is a need for more pragmatic randomised clinical trials
      conducted with low risks of systematic and random errors, and multinational
      cooperation is essential. CONCLUSIONS: The present paper presents major barriers
      to randomised clinical trials. It also underlines the value of using a pan
      European-distributed infrastructure to help investigators overcome barriers for
      multi-country trials in any disease area.

PMID- 28764810
TI  - CD106 is a novel mediator of bone marrow mesenchymal stem cells via NF-kappaB in
      the bone marrow failure of acquired aplastic anemia.
AB  - BACKGROUND: Acquired aplastic anemia (AA) is characterized by deficiency or
      dysfunction of the bone marrow (BM) microenvironment. However, little is known
      about the impairment of BM-derived mesenchymal stem cells (MSCs) in AA patients.
      METHODS: We used Illumina HiSeqTM 2000 sequencing, quantitative real-time
      polymerase chain reaction (qRT-PCR), flow cytometry (FCM), and Western blotting
      to test the expression of CD106 gene (vascular cell adhesion molecule 1 (VCAM1))
      and CD106 protein of BM-MSCs. Furthermore, we used hematoxylin and eosin (H&E)
      and histochemical staining analysis, immunofluorescence, and the formation of
      capillary-like structures to analyze capillary tube-like formation in vitro; we
      also used the Matrigel plug assay to test in vivo vasculogenesis, and an assay of
      colony forming units (CFUs) and colony-forming unit-megakaryocyte (CFU-MK) to
      detect the support function of MSCs in vitro. The in vivo engraftment of CD34+
      cells and MSCs in NOD/SCID mice was tested by FACS and survival assay; the
      expression of NF-kappaB was tested by NanoPro analysis and immunofluorescence. NF
      kappaB-regulated CD106 gene (VCAM1) was confirmed by tumor necrosis factor alpha
      (TNF-alpha)-stimulated and lipopolysaccharide (LPS)-stimulated MSCs, blockade
      assay, and immunofluorescence. RESULTS: Here, we report that BM-MSCs from AA
      patients exhibited downregulation of the CD06 gene (VCAM1) and low expression of
      CD106 in vitro. Further analysis revealed that CD106+ MSCs from both AA patients
      and healthy controls had increased potential for in vitro capillary tube-like
      formation and in vivo vasculogenesis compared with CD106- MSCs, and the results
      were similar when healthy MSCs were compared with AA MSCs. CD106+ MSCs from both
      AA patients and healthy controls more strongly supported in vitro growth and in
      vivo engraftment of CD34+ cells in NOD/SCID mice than CD106- MSCs, and similar
      results were obtained when healthy MSCs and AA MSCs were compared. The expression
      of NF-kappaB was decreased in AA MSCs, and NF-kappaB regulated the CD106 gene
      (VCAM1) which supported hematopoiesis. CONCLUSIONS: These results revealed the
      effect of CD106 and NF-kappaB in BM failure of AA.

PMID- 28764811
TI  - Survival impact of pre-treatment neutrophils on oropharyngeal and laryngeal
      cancer patients undergoing definitive radiotherapy.
AB  - BACKGROUND: Squamous cell carcinoma of the head and neck (HNSCC) represents an
      array of disease processes with a generally unfavorable prognosis. Inflammation
      plays an important role in tumor development and response to therapy. We
      performed a retrospective analysis of HNSCC patients to explore the relationship
      of the lymphocyte and neutrophil counts, the neutrophil-to-lymphocyte ratio (NLR)
      overall survival (OS), cancer-specific survival (CSS), local control (LC) and
      distant control (DC). MATERIALS/METHODS: All patients received definitive
      treatment for cancers of the oropharynx or larynx between 2006-2015. Neutrophil
      and lymphocyte counts were collected pre-, during-, and post-treatment. The
      correlations of patient, tumor, and biological factors to OS, CSS, LC and DC were
      assessed. RESULTS: 196 patients met our inclusion criteria; 171 patients were
      Stage III or IV. Median follow-up was 2.7 years. A higher neutrophil count at all
      treatment time points was predictive of poor OS with the pre-treatment neutrophil
      count and overall neutrophil nadir additionally predictive of DC. Higher pre
      treatment and overall NLR correlated to worse OS and DC, respectively.
      CONCLUSION: A higher pre-treatment neutrophil count correlates to poor OS, CSS
      and DC. Lymphocyte counts were not found to impact survival or tumor control.
      Higher pre-treatment NLR is prognostic of poor OS.

PMID- 28764813
TI  - An ontology-driven tool for structured data acquisition using Web forms.
AB  - BACKGROUND: Structured data acquisition is a common task that is widely performed
      in biomedicine. However, current solutions for this task are far from providing a
      means to structure data in such a way that it can be automatically employed in
      decision making (e.g., in our example application domain of clinical functional
      assessment, for determining eligibility for disability benefits) based on
      conclusions derived from acquired data (e.g., assessment of impaired motor
      function). To use data in these settings, we need it structured in a way that can
      be exploited by automated reasoning systems, for instance, in the Web Ontology
      Language (OWL); the de facto ontology language for the Web. RESULTS: We tackle
      the problem of generating Web-based assessment forms from OWL ontologies, and
      aggregating input gathered through these forms as an ontology of "semantically
      enriched" form data that can be queried using an RDF query language, such as
      SPARQL. We developed an ontology-based structured data acquisition system, which
      we present through its specific application to the clinical functional assessment
      domain. We found that data gathered through our system is highly amenable to
      automatic analysis using queries. CONCLUSIONS: We demonstrated how ontologies can
      be used to help structuring Web-based forms and to semantically enrich the data
      elements of the acquired structured data. The ontologies associated with the
      enriched data elements enable automated inferences and provide a rich vocabulary
      for performing queries.

PMID- 28764814
TI  - Differences of muscle co-contraction of the ankle joint between young and elderly
      adults during dynamic postural control at different speeds.
AB  - BACKGROUND: Agonist and antagonist muscle co-contractions during motor tasks are
      greater in the elderly than in young adults. During normal walking, muscle co
      contraction increases with gait speed in young adults, but not in elderly adults.
      However, no study has compared the effects of speed on muscle co-contraction of
      the ankle joint during dynamic postural control in young and elderly adults. We
      compared muscle co-contractions of the ankle joint between young and elderly
      subjects during a functional stability boundary test at different speeds.
      METHODS: Fifteen young adults and 16 community-dwelling elderly adults
      participated in this study. The task was functional stability boundary tests at
      different speeds (preferred and fast). Electromyographic evaluations of the
      tibialis anterior and soleus were recorded. The muscle co-contraction was
      evaluated using the co-contraction index (CI). RESULTS: There were no
      statistically significant differences in the postural sway parameters between the
      two age groups. Elderly subjects showed larger CI in both speed conditions than
      did the young subjects. CI was higher in the fast speed condition than in the
      preferred speed condition in the young subjects, but there was no difference in
      the elderly subjects. Moreover, after dividing the analytical range into phases
      (acceleration and deceleration phases), the CI was larger in the deceleration
      phase than in the acceleration phase in both groups, except for the young
      subjects in the fast speed conditions. CONCLUSIONS: Our results showed a greater
      muscle co-contraction of the ankle joint during dynamic postural control in
      elderly subjects than in young subjects not only in the preferred speed condition
      but also in the fast speed condition. In addition, the young subjects showed
      increased muscle co-contraction in the fast speed condition compared with that in
      the preferred speed condition; however, the elderly subjects showed no
      significant difference in muscle co-contraction between the two speed conditions.
      This indicates that fast movements cause different influences on dynamic postural
      control in elderly people, particularly from the point of view of muscle
      activation. These findings highlight the differences in the speed effects on
      muscle co-contraction of the ankle joint during dynamic postural control between
      the two age groups.

PMID- 28764812
TI  - Anopheles gambiae larvae mount stronger immune responses against bacterial
      infection than adults: evidence of adaptive decoupling in mosquitoes.
AB  - BACKGROUND: The immune system of adult mosquitoes has received significant
      attention because of the ability of females to vector disease-causing pathogens
      while ingesting blood meals. However, few studies have focused on the immune
      system of larvae, which, we hypothesize, is highly robust due to the high density
      and diversity of microorganisms that larvae encounter in their aquatic
      environments and the strong selection pressures at work in the larval stage to
      ensure survival to reproductive maturity. Here, we surveyed a broad range of
      cellular and humoral immune parameters in larvae of the malaria mosquito,
      Anopheles gambiae, and compared their potency to that of newly-emerged adults and
      older adults. RESULTS: We found that larvae kill bacteria in their hemocoel with
      equal or greater efficiency compared to newly-emerged adults, and that
      antibacterial ability declines further with adult age, indicative of senescence.
      This phenotype correlates with more circulating hemocytes and a differing spatial
      arrangement of sessile hemocytes in larvae relative to adults, as well as with
      the individual hemocytes of adults carrying a greater phagocytic burden. The
      hemolymph of larvae also possesses markedly stronger antibacterial lytic and
      melanization activity than the hemolymph of adults. Finally, infection induces a
      stronger transcriptional upregulation of immunity genes in larvae than in adults,
      including differences in the immunity genes that are regulated. CONCLUSIONS:
      These results demonstrate that immunity is strongest in larvae and declines after
      metamorphosis and with adult age, and suggest that adaptive decoupling, or the
      independent evolution of larval and adult traits made possible by metamorphosis,
      has occurred in the mosquito lineage.

PMID- 28764816
TI  - Genotyping of Bartonella bacteria and their animal hosts: current status and
      perspectives.
AB  - Growing evidence demonstrates that bacterial species diversity is substantial,
      and many of these species are pathogenic in some contexts or hosts. At the same
      time, laboratories and museums have collected valuable animal tissue and
      ectoparasite samples that may contain substantial novel information on bacterial
      prevalence and diversity. However, the identification of bacterial species is
      challenging, partly due to the difficulty in culturing many microbes and the
      reliance on molecular data. Although the genomics revolution will surely add to
      our knowledge of bacterial systematics, these approaches are not accessible to
      all researchers and rely predominantly on cultured isolates. Thus, there is a
      need for comprehensive molecular analyses capable of accurately genotyping
      bacteria from animal tissues or ectoparasites using common methods that will
      facilitate large-scale comparisons of species diversity and prevalence. To
      illustrate the challenges of genotyping bacteria, we focus on the genus
      Bartonella, vector-borne bacteria common in mammals. We highlight the value and
      limitations of commonly used techniques for genotyping bartonellae and make
      recommendations for researchers interested in studying the diversity of these
      bacteria in various samples. Our recommendations could be applicable to many
      bacterial taxa (with some modifications) and could lead to a more complete
      understanding of bacterial species diversity.

PMID- 28764817
TI  - The RPMI-1640 vitamin mixture promotes bovine blastocyst development in vitro and
      downregulates gene expression of TXNIP with epigenetic modification of associated
      histones.
AB  - Diverse environmental conditions surrounding preimplantation embryos, including
      available nutrients, affect their metabolism and development in both short- and
      long-term manner. Thioredoxin-interacting protein (TXNIP) is a possible marker
      for preimplantation stress that is implicated in in vitro fertilization- (IVF)
      induced long-term DOHaD effects. B vitamins, as participants in one-carbon
      metabolism, may affect preimplantation embryos by epigenetic alterations of
      metabolically and developmentally important genes. In vitro-produced bovine
      embryos were cultured with or without Roswell Park Memorial Institute 1640
      vitamin mixture, containing B vitamins and B vitamin-like substances, from day 3
      after IVF and we evaluated blastocyst development and TXNIP messenger RNA (mRNA)
      expression in the blastocysts by reverse transcription-quantitative polymerase
      chain reaction. The degree of trimethylation of histone H3 lysine 27 (H3K27me3)
      at TXNIP promoter was examined semi-quantitatively by chromatin
      immunoprecipitation polymerase chain reaction. Total H3K27me3 were also compared
      between the groups by Western blot analysis. The vitamin treatment significantly
      increased the rates of blastocyst development (P<0.05) and their hatching
      (P<0.001) from the zona pellucida by day 8. The mRNA expression of TXNIP was
      lower (P<0.01) in blastocysts in the vitamin-mixture-treated group concomitant
      with higher (P<0.05) level of H3K27me3 of its promoter compared with the control
      group. The total H3K27me3 in the vitamin-mixture-treated group was also higher
      (P<0.01) than that in the control group. The epigenetic control of genes related
      to important metabolic processes during the periconceptional period by
      nutritional conditions in utero and/or in vitro may have possible implication for
      the developmental programming during this period that may impact the welfare and
      production traits of farm animals.

PMID- 28764815
TI  - A proteomic insight into the midgut proteome of Ornithodoros moubata females
      reveals novel information on blood digestion in argasid ticks.
AB  - BACKGROUND: The argasid tick Ornithodoros moubata is the main African vector of
      the human relapsing fever agent Borrelia duttoni and the African swine fever
      virus. Together with saliva, the tick midgut forms part of the host-tick-pathogen
      interface, and numerous midgut proteins play key functions in the blood digestion
      related process and the infection and transmission of pathogens. This work
      explores the composition of the midgut proteome of unfed and fed O. moubata
      females with the aim to complete the biological information already obtained from
      the midgut transcriptome and provide a more robust and comprehensive perspective
      of this biological system. METHODS: Midgut tissues taken from females before
      feeding and 48 h after feeding were subjected to LC/MS-MS analysis. After
      functional characterization and classification of the proteins identified, the
      differences in the proteome between unfed and fed females were analysed and
      discussed. Additionally, a detailed analysis of particular groups of proteins
      that are involved in the processes of nutrient digestion and responses to the
      oxidative stress was carried out. RESULTS: 1491 non-redundant tick proteins were
      identified: 1132 of them in the midgut of unfed ticks, 1138 in the midgut of fed
      ticks, and up to 779 shared by both physiological conditions. Overall, the
      comparative analysis of the midgut proteomes of O. moubata females before and
      after feeding did not reveal great differences in the number or class of proteins
      expressed, enzymatic composition or functional classification. CONCLUSIONS: The
      hemoglobinolytic system in ixodids and argasids is very similar in spite of the
      fact that they display very different feeding and reproductive strategies.
      Although the main source of nutrients in ticks are proteins, lipids and
      carbohydrates also constitute significant nutritional sources and play an
      important part in the process of blood digestion. The genes and proteins involved
      in intracellular transport mechanisms, defensive responses, detoxifying responses
      and stress responses seem to be closely regulated, highlighting the complexity
      and importance of these processes in tick biology, which in turn assigns them a
      great interest as targets for therapeutic and immunological interventions.

PMID- 28764818
TI  - Emergency Response of Iranian Hospitals Against Disasters: A Practical Framework
      for Improvement.
AB  - OBJECTIVE: Hospital emergency management is a continuous process that requires
      monolithic integration of planning and response attempts with local and national
      schemes. The aim of the current study is to evaluate emergency response by
      hospitals against potential disasters in Tabriz, north-west Iran. METHODS: A
      cross-sectional study was conducted in the city of Tabriz, in Iran, in 2016. The
      study population included all hospitals in Tabriz. A total of 18 hospitals were
      assessed. The hospital emergency response checklist was used to collect data.
      Tool components included command and control, communication, safety and security,
      triage, surge capacity, continuity of essential services, human resources,
      logistics and supply management, and post-disaster recovery. Data entry and
      analysis were carried out using SPSS software (version 20). RESULTS: The results
      showed that the emergency response rate of hospitals was 54.26% in Tabriz. The
      lowest response rates were for Shafaa hospital (18.89%) and the highest response
      rates were for Razi Hospital (91.67%). The components of hospital emergency
      response were assessed to be between 48.07% (surge capacity) and 58.95%
      (communication). CONCLUSION: On the basis of the World Health Organization
      checklist, the emergency response rate for hospitals in Tabriz was only 54.26%.
      Therefore, hospital emergency responses against disasters have to be improved and
      must be made to reach 100%. It is essential to design a comprehensive framework
      for hospital emergency response. (Disaster Med Public Health Preparedness.
      2018;12:166-171).

PMID- 28764819
TI  - SEX COMPOSITION OF TWINS AND ASSOCIATIONS WITH MORBIDITY, MORTALITY AND MATERNAL
      TREATMENT-SEEKING OUTCOMES IN RESOURCE-POOR SETTINGS.
AB  - SummarySocietal gender inequality and a preference for male children has been
      shown to be detrimental to girls' health. This is despite females' innate
      biological advantage early in life. The negative effects of gender inequity on
      female health are most pronounced in resource-poor countries, where cultural
      norms supporting a preference for male children are strongest. However, most of
      what is known about gender inequality and child health comes from studies of
      singleton births. There is little evidence for how, or if, the disadvantages
      associated with gender bias and son preference extend to multiple births, a
      population inherently at risk for a number of health challenges. This analysis
      examines whether gender bias in health outcomes exists for twins. Data on live
      twin births from 38 Demographic and Health Surveys were compiled (n=11,528
      individuals) and twins were categorized as girl/girl, girl/boy, boy/girl or
      girl/girl. Gender inequality was measured via the Gender Inequality Index.
      Multilevel logistic regression models examined associations between twin sex
      composition, gender inequality and eight outcomes of infant and child morbidity,
      mortality and mother's treatment-seeking behaviours. Twin pairs containing girls
      had significantly lower odds of first-year mortality. Higher country-level gender
      inequality was associated with higher odds of reporting diarrhoea and
      fever/cough, as well as an increased odds of post-neonatal mortality. Results
      suggest that the biological advantage for females may be stronger than son
      preference and gender inequality in the first year of life. Understanding these
      relationships has the potential to inform efforts to curb the influence of gender
      preference on the health of female children in resource-poor settings.

PMID- 28764820
TI  - Getting Noticed.

PMID- 28764821
TI  - Investigating the Role of Near-Infrared Spectroscopy in Neonatal Medicine.
AB  - Near-infrared spectroscopy (NIRS) is a clinical tool that provides a bedside
      method of noninvasively measuring continuous, "real-time" oxygen consumption and
      monitoring for potential ischemia of somatic tissues, particularly the brain,
      kidneys, and intestine in neonates. Although the concept of NIRS seems promising,
      its implementation into clinical practice has been inconsistent for various
      reasons, including difficulty in interpreting regional oxygen saturation (rSO2),
      the wide variation in types of NIRS monitors and probes, the cost of new
      equipment, different monitoring modalities, large discrepancies in both intra-
      and interindividual use, a lack of defined universal normative values, and little
      to no data on outcomes or potentially harmful interventions made based on rSO2
      readings. We combine findings from previously published informational articles
      and studies on the use of NIRS in neonatal medicine to provide a comprehensive
      overview of this tool and identify potential indications for clinical use.

PMID- 28764822
TI  - Transient Neonatal Diabetes Mellitus: A Challenge and Opportunity for Specialized
      Nursing Care.
AB  - Transient neonatal diabetes mellitus (TNDM) is a rare disorder, with a reported
      incidence of approximately 1 in 450,000 live births. It is characterized by
      insulin-requiring hyperglycemia in the neonatal period. The disease improves by
      early childhood, but the patient may relapse in later life. Diagnosis is made
      after genetic testing following presentation with hyperglycemia not conforming to
      Type 1 or Type 2 diabetes. Management is based on insulin and possible
      sulfonylurea administration. Three genetically distinct subtypes of TNDM are
      recognized. Type 1 TNDM is due to overexpression of genes at the 6q24 locus,
      whereas the 11p15 locus is involved in Type 2 and 3 TNDM. In this article the
      clinical presentation, management, and genetics of TNDM are discussed,
      particularly emphasizing the role of the neonatal nurse.

PMID- 28764823
TI  - Silver-Russell Syndrome: A Review.
AB  - Silver-Russell syndrome (SRS) is a rare congenital imprinting disorder. The
      genetic findings in SRS patients are heterogeneous and often sporadic. However,
      chromosomes 7, 11, and 17 are consistently involved in all individuals who meet
      the strict diagnostic criteria of SRS. There are many clinical features
      characteristic of SRS; the most common are low birth weight, short stature,
      triangular face, clinodactyly, relative macrocephaly, ear anomalies, and skeletal
      asymmetry.

PMID- 28764824
TI  - Music in the NICU: The Role of Nurses in Neuroprotection.
AB  - Early exposure to age-appropriate, meaningful auditory stimuli, such as lullaby
      singing, has been shown to advance various medical and developmental goals in
      premature infants in the NICU while reducing medical costs. A primary goal of
      NICU music therapists is to control auditory stimuli in the unit to help
      premature infants reach the greatest possible sedation. In hospitals with limited
      or no NICU music therapy (NICU-MT) coverage, nurses and other NICU staff can play
      an important role in providing neuroprotection to these premature infants while
      also optimizing neurodevelopment via use of recorded music. Based on current
      literature, this article provides a set of evidence-based guidelines for the use
      of recorded music with premature infants.

PMID- 28764825
TI  - Living with Tricuspid Atresia: Case Report with Review of Literature.
AB  - Tricuspid atresia (TA) is a rare congenital heart defect in which the right
      atrioventricular connection, the tricuspid valve, is absent. As a result, there
      is no direct communication between the right atrium and right ventricle. Surgical
      treatment, including the Fontan procedure, is indicated yet palliative, leaving
      patients with various lifelong complications. A comprehensive literature review
      revealed a paucity of evidence-based education on the identification, evaluation,
      management, treatment, and life span implications of TA. We present a case of TA
      from birth through adulthood, while simultaneously assessing the literature, to
      report the most current evidence relative to living with TA after surgical
      palliation. In addition, the embryology, methods of prenatal and postnatal
      diagnosis, potential complications, management, anticipatory guidance, and
      educational needs of both parents and patient are discussed.

PMID- 28764826
TI  - Minding the Gap: Utility of the Anion Gap in the Differential Diagnosis of
      Metabolic Acidosis.
AB  - The anion gap, in conjunction with other laboratory results, can be a useful clue
      in the differential diagnosis of metabolic acidosis. There are three primary
      causes of metabolic acidosis: loss of base, decreased renal excretion of acid,
      and increased acid production. Depending on the cause of metabolic acidosis, the
      anion gap may be elevated or normal.

PMID- 28764827
TI  - Using Dextrose (Glucose) Gel to Reverse Neonatal Hypoglycemia.
AB  - Hospitals are challenged to implement measures to improve health outcomes,
      decrease costly interventions, and increase patient satisfaction. By following a
      nurse-driven protocol, our institution has successfully met these three
      challenges in our treatment of newborns diagnosed with neonatal hypoglycemia
      (NH). Based on results of a randomized clinical trial, a multidisciplinary team
      trialed glucose gel as a standard treatment for NH. During the first year,
      admission rates to the NICU for NH decreased by 73 percent. Exclusive
      breastfeeding rates for this population increased to 49 percent and 40 additional
      families remained together on the mother baby unit. This practice change is
      improving health outcomes, decreasing expensive interventions, and increasing
      satisfaction among the population of infants at risk for NH.

PMID- 28764828
TI  - The Infant Born to a Woman with Gestational Diabetes.
AB  - Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset
      during pregnancy. During pregnancy, women with GDM develop insulin resistance,
      which results in altered glucose tolerance. As a result, there are frequent
      episodes of hyperglycemia and high levels of circulating amino acids, increasing
      the transfer of nutrients to the fetus. This article discusses the role of the
      mother-baby nursing in the care of neonates born to women with gestational
      diabetes.

PMID- 28764830
TI  - Continuing Education Course.

PMID- 28764831
TI  - News of the Academy of Neonatal Nursing.

PMID- 28764832
TI  - Conference Proceedings.

PMID- 28764833
TI  - The Separation of Septic and Aseptic Surgical Areas is Obsolete.

PMID- 28764835
TI  - The Cobblestone Sign in a Child with Crohn's Disease.

PMID- 28764834
TI  - Microbial Load in Septic and Aseptic Procedure Rooms.
AB  - BACKGROUND: Highly effective measures to prevent surgical wound infections have
      been established over the last two decades. We studied whether the strict
      separation of septic and aseptic procedure rooms is still necessary. METHODS: In
      an exploratory, prospective observational study, the microbial concentration in
      an operating room without a room ventilating system (RVS) was analyzed during 16
      septic and 14 aseptic operations with the aid of an air sampler (50 cm and 1 m
      from the operative field) and sedimentation plates (1 m from the operative field,
      and contact culture on the walls). The means and standard deviations of the
      microbial loads were compared with the aid of GEE models (generalized estimation
      equations). RESULTS: In the comparison of septic and aseptic operations, no
      relevant differences were found with respect to the overall microbial
      concentration in the room air (401.7 +/- 176.3 versus 388.2 +/- 178.3 CFU/m3; p =
      0.692 [CFU, colony-forming units]) or sedimentation 1 m from the operative field
      (45.3 +/- 22.0 versus 48.7 +/- 18.5 CFU/m2/min; p = 0.603) and on the walls (35.7
      +/- 43.7 versus 29.0 +/- 49.4 CFU/m2/min; p = 0.685). The only relevant
      differences between the microbial spectra associated with the two types of
      procedure were a small amount of sedimentation of Escherichia coli and
      Enterococcus faecalis in septic operations, and of staphylococcus aureus and
      pseudomonas stutzeri in aseptic operations, up to 30 minutes after the end of the
      procedure. CONCLUSION: These data do not suggest that septic and aseptic
      procedure rooms need to be separated. In interpreting the findings, one should
      recall that the study was not planned as an equivalence or non-inferiority study.
      Wherever patient safety is concerned, high-level safety concepts should only be
      demoted to lower levels if new and convincing evidence becomes available.

PMID- 28764836
TI  - Aspirin Before Elective Surgery-Stop or Continue?
AB  - BACKGROUND: Cessation of long-term aspirin treatment before noncardiac surgery
      can cause adverse cardiac events in patients at risk, particularly in those with
      previous percutaneous coronary interventions (PCI) with stent implantation. The
      factors influencing the clinical decision to stop aspirin treatment are currently
      unknown. METHODS: In a single-center, cross-sectional study (retrospective
      registration: NCT03049566) carried out from February to December 2014, we took a
      survey among patients scheduled for noncardiac surgery who were under long-term
      aspirin treatment, and among their treating anesthesiologists using standardized
      questionnaires on preoperative aspirin use, comorbidities, and risk-benefit
      assessments. The main objective was to identify factors associated with the
      decision to stop aspirin treatment. The results of multivariable logistic
      regressions and intraclass correlations are presented. RESULTS: 805 patients were
      included in the study, and 636 questionnaires were returned (203 of which
      concerned patients with coronary stents). 46.8% of the patients stopped their
      long-term aspirin treatment before surgery; 38.7% of these patients stopped it
      too early (>10 days before surgery) or too late (<= 3 days before surgery). A
      prior PCI with stent implantation lowered the probability of aspirin cessation
      (odds ratio [OR] = 0.47 [0.31; 0.72]; p <0.001). On the other hand, patients were
      more likely to stop their long-term aspirin treatment if it had already been
      discontinued once before (OR = 4.58 [3.06; 6.84]; p <0.001), if there was a risk
      of bleeding into a closed space (OR = 4.54 [2.02; 10.22]; p <0.001), if they did
      not know why they were supposed to take aspirin (OR = 2.12 [1.05; 4.28]; p =
      0.036), or if the preoperative consultation with the anesthesiologist occurred <2
      days before surgery (OR = 1.60 [1.08; 2.37]; p = 0.018). Patients often assessed
      the risks related to aspirin cessation lower than their physicians did.
      CONCLUSION: This study reveals discordance between guideline recommendations and
      everyday clinical practice in patients with coronary stents. The early
      integration of cardiologists and anesthesiologists and a more widespread use of
      stent implant cards could promote adherence to the guidelines.

PMID- 28764837
TI  - Supportive Treatments for Patients with Cancer.
AB  - BACKGROUND: For the treatment of patients with cancer to be successful and well
      tolerated, the complications and side effects of the disease and its treatment
      must be treated and limited as far as possible. Summarized recommendations based
      on the constantly increasing evidence in the area of supportive care must be
      defined, standardized, and communicated. METHODS: We systematically reviewed the
      literature on the topics of anemia, neutropenia, nausea/vomiting, diarrhea, oral
      mucositis, skin toxicity, and peripheral neurotoxicity induced by cancer
      treatment, as well as osseous complications, extravasation, and side effects of
      radiotherapy. Recommendations were approved in a moderated, formalized consensus
      procedure. RESULTS: In patients suffering from chemotherapy-induced anemia, the
      administration of agents that stimulate erythropoiesis can be considered. This
      can potentially improve these patients' quality of life and lessen the frequency
      of blood transfusions, but it can also lead to thromboembolic complications and
      arterial hypertension. If only a single individual risk factor is present in a
      patient whose risk of febrile neutropenia is estimated at 10-20%, there is no
      obligatory indication for the administration of granulocyte-colony stimulating
      factor. Antiemetic treatment before carboplatin is given can consist of a
      neurokinin-1 receptor antagonist along with a setron and dexamethasone.
      Duloxetine is recommended for the treatment of neuropathic pain. Sensorimotor
      training is effective in the treatment of chemotherapy-induced peripheral
      neuropathy and can already be given at the same time as the chemotherapy. Women
      with bony metastases of breast cancer who have been taking zoledronate at four
      week intervals for a year should take it at 12-week intervals from then onward in
      order to lessen the likelihood of osseus complications. There is no evidence for
      any effective prophylactic treatment of chemotherapy-induced diarrhea.
      CONCLUSION: Supportive measures are an integral component of all oncological
      treatments. More research is needed to determine how side effects can be lessened
      and prevented.

PMID- 28764838
TI  - Additional Points Need to Be Raised.

PMID- 28764839
TI  - In Reply.

PMID- 28764840
TI  - Foreword.

PMID- 28764841
TI  - Non-ST Elevation Acute Coronary Syndromes: A Comprehensive Review.
AB  - Non-ST elevation-acute coronary syndrome (NSTE-ACS) includes NSTE myocardial
      infarction and unstable angina. This patient population forms approximately two
      thirds of all hospital admissions for ACS in the United States each year and is
      associated with an in-hospital mortality of 5%. NSTE-ACS is primarily due to an
      acute change in the supply and demand balance of coronary perfusion and
      myocardial oxygen consumption, because of the significant coronary artery
      obstruction presenting as plaque rupture or erosion. Nevertheless, nonobstructive
      causes may lead to that same phenomenon by excessive myocardial oxygen demand or
      reduced coronary supply from hypotension, anemia, or sepsis, including transient
      coronary vasospasm and endocardial dysfunction. The recent clinical application
      of high-sensitivity troponin biomarker assays and computer tomography angiography
      shows promise for improving the diagnosis and the risk stratification of patients
      with angina symptoms. Implementation of recent updates to the American College of
      Cardiology/American Heart Association (ACC/AHA) guidelines on NSTE-ACS,
      especially regarding the selection and duration of antiplatelet therapy, have led
      to improvement in management and outcomes of this disease. Additionally, new
      adjunctive therapies and approaches to diagnosis and treatment are discussed.
      Despite the progress made in recent years in the diagnosis and management of NSTE
      ACS, morbidity remains high and mortality is significant. Such a fact suggests
      that future research targeting prevention, early diagnosis, and intervention in
      these patients is warranted. This article provides a detailed overview of the
      most recent information on the pathophysiology, diagnosis, treatment, and
      prognosis of NSTE-ACS.

PMID- 28764842
TI  - The ontogeny of learning and memory.

PMID- 28764843
TI  - Current role of the NLRP3 inflammasome on obesity and insulin resistance: A
      systematic review.
AB  - NLRP3 inflammasome activation seems to be a culprit behind the chronic
      inflammation characteristic of obesity and insulin resistance (IR). Nutrient
      excess generates danger-associated molecules that activate NLRP3 inflammasome
      caspase 1, leading to maturation of IL-1beta and IL-18, which are proinflammatory
      cytokines released by immune cells infiltrating the adipose tissue (AT) from
      obese subjects. Although several studies have reported an association of the
      NLRP3 inflammasome with obesity and/or IR; contradictory results were also
      reported by other studies. Therefore, we conducted a systematic review to
      summarize results of studies that evaluated the association of the NLRP3 with
      obesity and IR. Nineteen studies were included in the review. These studies
      focused on NLRP3 expression/polymorphism analyses in AT. Overall, human studies
      indicate that obesity and IR are associated with increased NLRP3 expression in
      AT. Studies in obese mice corroborate this association. Moreover, high fat diet
      (HFD) increases Nlrp3 expression in murine AT while calorie-restricted diet
      decreases its expression. Hence, Nlrp3 blockade in mice protects against HFD
      induced obesity and IR. NLRP3 rs10754558 polymorphism is associated with risk for
      T2DM in Chinese Han populations. In conclusion, available studies strongly points
      for an association between NLRP3 inflammasome and obesity/IR.

PMID- 28764844
TI  - Biliopancreatic diversion with duodenal switch leads to better postprandial
      glucose level and beta cell function than sleeve gastrectomy in individuals with
      type 2 diabetes very early after surgery.
AB  - OBJECTIVE: The aim of this study was to compare the short-term effect of sleeve
      gastrectomy (SG) and biliopancreatic diversion with duodenal switch (DS) in order
      to determine if exclusion of the upper gastrointestinal tract confers greater
      metabolic improvement, independent of weight loss. METHODS: Standard meals were
      administered before and on day 3 and 4 after SG to assess insulin sensitivity,
      beta-cell function and gastrointestinal hormone responses in matched
      normoglycemic (NG) and type 2 diabetes (T2D) participants. A third group of
      matched T2D participants who underwent DS with the same meal test administered
      prior to and 3days after surgery was also recruited. RESULTS: Despite significant
      metabolic improvement, T2D participants failed to fully normalize insulin
      resistance and beta-cell dysfunction 3 and 4days after SG. Our results
      demonstrate the superiority of DS over SG in terms of short-term improvement in
      postprandial glucose excursion and beta-cell function 3days after the surgery,
      with similar improvement in hepatic insulin sensitivity. CONCLUSION: Our findings
      support the notion that caloric restriction represents an important mechanism to
      explain the very early anti-diabetic effects observed after bariatric surgery.
      However, exclusion of the upper gastrointestinal tract also provides further
      metabolic improvements, possibly mediated by gastrointestinal hormonal responses
      and altered postprandial glucose absorption.

PMID- 28764845
TI  - Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT)
      patients with low bone mineral density.
AB  - CONTEXT: A subset of PHPT patients exhibit a more severe disease phenotype
      characterized by bone loss, fractures, recurrent nephrolithiasis, and other
      dysfunctions, but the underlying reasons for this disparity in clinical
      presentation remain unknown. OBJECTIVE: We sought to identify new mechanistic
      indices that could inform more personalized management of PHPT. DESIGN: Pre-,
      peri-, and postoperative data and demographic, clinical, and pathological
      information from patients undergoing parathyroidectomy for PHPT were collected.
      Univariate and partial Spearman correlation was used to estimate the association
      of parathyroid tumor calcium sensing capacity with select variables. PATIENTS OR
      OTHER PARTICIPANTS: An unselected series of 237 patients aged >18years and
      undergoing parathyroidectomy for PHPT were enrolled. MAIN OUTCOME MEASURES:
      Calcium sensing capacity, expressed as the concentration required for half
      maximal biochemical response (EC50), was evaluated in parathyroid tumors from an
      unselected series of 74 patients and assessed for association with clinical
      parameters. The hypothesis was that greater disease severity would be associated
      with attenuated calcium sensitivity and biochemically autonomous parathyroid
      tumor behavior. RESULTS: Parathyroid tumors segregated into two distinct groups
      of calcium responsiveness (EC50<3.0 and >=3.0mM). The low EC50 group (n=27)
      demonstrated a mean calcium EC50 value of 2.49mM [95% confidence interval (CI):
      2.43-2.54mM], consistent with reference normal activity. In contrast, the high
      EC50 group (n=47) displayed attenuated calcium sensitivity with a mean EC50 value
      of 3.48mM [95% CI: 3.41-3.55mM]. Retrospective analysis of the clinical registry
      data suggested that high calcium EC50 patients presented with a more significant
      preoperative bone mineral density (BMD) deficit with a t-score of -2.7, (95% CI: 
      3.4 to -1.9) versus 0.9, (95% CI: -2.1 to -0.4) in low EC50 patients (p<0.001).
      After adjusting for gender, age, BMI, 25 OH vitamin D level and preoperative
      iPTH, lowest t-score and calcium EC50 were inversely correlated, with a partial
      Spearman correlation coefficient of -0.35 (p=0.02). CONCLUSIONS: Impaired calcium
      sensing in parathyroid tumors is selectively observed in a subset of patients
      with more severe bone mineral density deficit. Assessment of parathyroid tumor
      biochemical behavior may be a useful predictor of disease severity as measured by
      bone mineral density in patients with PHPT.

PMID- 28764847
TI  - Corrigendum to "Assessment of common variability and expression quantitative
      trait loci for genome-wide associations for progressive supranuclear palsy."
      [Neurobiol. Aging 35 (2014) 1514.e1-1514.e12].

PMID- 28764848
TI  - Integrative analysis of omics data.

PMID- 28764846
TI  - Uric acid promotes vascular stiffness, maladaptive inflammatory responses and
      proteinuria in western diet fed mice.
AB  - OBJECTIVE: Aortic vascular stiffness has been implicated in the development of
      cardiovascular disease (CVD) and chronic kidney disease (CKD) in obese
      individuals. However, the mechanism promoting these adverse effects are unclear.
      In this context, promotion of obesity through consumption of a western diet (WD)
      high in fat and fructose leads to excess circulating uric acid. There is
      accumulating data implicating elevated uric acid in the promotion of CVD and CKD.
      Accordingly, we hypothesized that xanthine oxidase(XO) inhibition with
      allopurinol would prevent a rise in vascular stiffness and proteinuria in a
      translationally relevant model of WD-induced obesity. MATERIALS/METHODS: Four
      week-old C57BL6/J male mice were fed a WD with excess fat (46%) and fructose
      (17.5%) with or without allopurinol (125mg/L in drinking water) for 16weeks.
      Aortic endothelial and extracellular matrix/vascular smooth muscle stiffness was
      evaluated by atomic force microscopy. Aortic XO activity, 3-nitrotyrosine (3-NT)
      and aortic endothelial sodium channel (EnNaC) expression were evaluated along
      with aortic expression of inflammatory markers. In the kidney, expression of toll
      like receptor 4 (TLR4) and fibronectin were assessed along with evaluation of
      proteinuria. RESULTS: XO inhibition significantly attenuated WD-induced increases
      in plasma uric acid, vascular XO activity and oxidative stress, in concert with
      reductions in proteinuria. Further, XO inhibition prevented WD-induced increases
      in aortic EnNaC expression and associated endothelial and subendothelial
      stiffness. XO inhibition also reduced vascular pro-inflammatory and maladaptive
      immune responses induced by consumption of a WD. XO inhibition also decreased WD
      induced increases in renal TLR4 and fibronectin that associated proteinuria.
      CONCLUSIONS: Consumption of a WD leads to elevations in plasma uric acid,
      increased vascular XO activity, oxidative stress, vascular stiffness, and
      proteinuria all of which are attenuated with allopurinol administration.

PMID- 28764849
TI  - Correction.

PMID- 28764850
TI  - Surgical registrars' perceptions of surgical training and capacity in Zambia:
      Results from three COSECSA affiliated training hospitals.
AB  - BACKGROUND: Surgery is a vital component of a comprehensive health system, but
      there are often personnel limitations in resource constrained areas. Zambia
      provides post graduate surgical training through two systems to help address this
      shortage. However, no studies have analyzed surgical trainees' perceptions of
      these programs. METHODS: Surgical registrars at COSECSA affiliated hospitals in
      Zambia were surveyed about their programs. Responses were analyzed to identify
      key strengths and challenges across several categories including: operative
      training, clinical training, educational experiences, and career plans. RESULTS:
      Registrars report having significant independence and receiving broad and high
      quality operative training. They note specific challenges including limitations
      in specialty training, resources, and infrastructure. CONCLUSIONS: Zambian
      training programs have the potential to increase number of surgeons in Zambia by
      a significant amount in the coming years. These programs have many strengths but
      also face challenges in their goal to expand surgical access in the country.

PMID- 28764851
TI  - Errors in accident data, its types, causes and methods of rectification-analysis
      of the literature.
AB  - Most of the decisions taken to improve road safety are based on accident data,
      which makes it the back bone of any country's road safety system. Errors in this
      data will lead to misidentification of black spots and hazardous road segments,
      projection of false estimates pertinent to accidents and fatality rates, and
      detection of wrong parameters responsible for accident occurrence, thereby making
      the entire road safety exercise ineffective. Its extent varies from country to
      country depending upon various factors. Knowing the type of error in the accident
      data and the factors causing it enables the application of the correct method for
      its rectification. Therefore there is a need for a systematic literature review
      that addresses the topic at a global level. This paper fulfils the above research
      gap by providing a synthesis of literature for the different types of errors
      found in the accident data of 46 countries across the six regions of the world.
      The errors are classified and discussed with respect to each type and analysed
      with respect to income level; assessment with regard to the magnitude for each
      type is provided; followed by the different causes that result in their
      occurrence, and the various methods used to address each type of error. Among
      high-income countries the extent of error in reporting slight, severe, non-fatal
      and fatal injury accidents varied between 39-82%, 16-52%, 12-84%, and 0-31%
      respectively. For middle-income countries the error for the same categories
      varied between 93-98%, 32.5-96%, 34-99% and 0.5-89.5% respectively. The only four
      studies available for low-income countries showed that the error in reporting non
      fatal and fatal accidents varied between 69-80% and 0-61% respectively. The
      logistic relation of error in accident data reporting, dichotomised at 50%,
      indicated that as the income level of a country increases the probability of
      having less error in accident data also increases. Average error in recording
      information related to the variables in the categories of location, victim's
      information, vehicle's information, and environment was 27%, 37%, 16% and 19%
      respectively. Among the causes identified for errors in accident data reporting,
      Policing System was found to be the most important. Overall 26 causes of errors
      in accident data were discussed out of which 12 were related to reporting and 14
      were related to recording. "Capture-Recapture" was the most widely used method
      among the 11 different methods: that can be used for the rectification of under
      reporting. There were 12 studies pertinent to the rectification of accident
      location and almost all of them utilised a Geographical Information System (GIS)
      platform coupled with a matching algorithm to estimate the correct location. It
      is recommended that the policing system should be reformed and public awareness
      should be created to help reduce errors in accident data.

PMID- 28764852
TI  - Parkinson's disease compromises the appraisal of action meanings evoked by
      naturalistic texts.
AB  - The linguistic profile of Parkinson's disease (PD) is characterized by
      difficulties in processing units which denote bodily movements. However, the
      available evidence has low ecological validity, as it stems from atomistic tasks
      which are never encountered in real life. Here, we assessed whether such deficits
      also occur for meanings evoked by context-rich narratives, considering patients
      with and without mild cognitive impairment (PD-MCI and PD-nMCI, respectively) and
      matched controls for each group. Participants read two naturalistic stories (an
      action text and a neutral text) and responded to questions tapping the appraisal
      of verb-related and circumstantial information. In PD-MCI, impairments in the
      appraisal of action meanings emerged alongside difficulties in other categories,
      but they were unique in their independence from general cognitive dysfunction.
      However, in PD-nMCI, deficits were observed only for action meanings,
      irrespective of the patients' domain-general skills (executive functions and
      general cognitive state). Also, using multiple group discriminant function
      analyses, we found that appraisal of action meanings was the only discourse-level
      variable that robustly contributed to classifying PD-MCI patients from controls
      (with an accuracy of 88% for all participants and for each sample separately).
      Moreover, this variable actually superseded a sensitive executive battery in
      discriminating between PD-nMCI and controls (with a combined accuracy of 83% for
      all participants, correctly classifying 79.2% of patients and 87.5% of controls).
      In sum, action appraisal deficits seem to constitute both a hallmark of
      naturalistic discourse processing in PD and a sensitive subject-level marker for
      patients with and without MCI. Such findings highlight the relevance of
      ecological measures of embodied cognitive functions in the assessment of this
      population.

PMID- 28764853
TI  - A revised method for the preparation of dry bone samples used in histological
      examination: Five simple steps.
AB  - Histology of dry bone tissue has many scientific applications. The histological
      analysis of bone requires the production of good quality thin sections. Many
      researchers have developed new histological techniques and/or they have refined
      existing ones. In this paper, we describe a revision of histological techniques
      for obtaining thin sections from modern dry bone. The method is easy to apply and
      the equipment required is commonly found in a histology laboratory. In comparison
      to other techniques presented in the literature, this adapted method reduces the
      number of consumables and steps, thereby improving the efficiency and cost
      effectiveness of the procedure.

PMID- 28764854
TI  - Probing foam with neutrons.
AB  - Foams are multiscale materials that have an enormous number of uses. As the
      relevant structural length-scales span from a few nanometres up to millimetres a
      number of characterisation methods need to be combined to obtain the full
      material structure. In this review we explain how foams can be explored using
      Small Angle Neutron Scattering (SANS). We remind the reader of the basics of SANS
      and contrast variation before we describe the different types of experiments that
      have been carried out on foams emphasising the specific role of neutrons in
      learning about the systems. To date SANS has been used to measure different foam
      structural parameters, such as the film thickness and the bubble size. Several
      studies have also been carried out to elucidate the organisation of the
      stabilising objects in the bulk solution. Finally we show how SANS measurements
      can be used to measure foam composition. Some of the accessible information is
      unique to SANS experiments, but as the method is still not very widely used on
      foams the review is also aimed to act as an introduction on how to carry out such
      measurements on foams.

PMID- 28764855
TI  - A data-driven fault-tolerant control design of linear multivariable systems with
      performance optimization.
AB  - In this paper, an integrated data-driven fault-tolerant control (FTC) design
      scheme is proposed under the configuration of the Youla parameterization for
      multiple-input multiple-output (MIMO) systems. With unknown system model
      parameters, the canonical form identification technique is first applied to
      design the residual observer in fault-free case. In faulty case, with online
      tuning of the Youla parameters based on the system data via the gradient-based
      algorithm, the fault influence is attenuated with system performance
      optimization. In addition, to improve the robustness of the residual generator to
      a class of system deviations, a novel adaptive scheme is proposed for the
      residual generator to prevent its over-activation. Simulation results of a two
      tank flow system demonstrate the optimized performance and effect of the proposed
      FTC scheme.

PMID- 28764856
TI  - Image quality of CT angiography in young children with congenital heart disease:
      a comparison between the sinogram-affirmed iterative reconstruction (SAFIRE) and
      advanced modelled iterative reconstruction (ADMIRE) algorithms.
AB  - AIM: To compare the image quality of computed tomography angiography (CTA)
      reconstructed by sinogram-affirmed iterative reconstruction (SAFIRE) with that of
      advanced modelled iterative reconstruction (ADMIRE) in children with congenital
      heart disease (CHD). MATERIAL AND METHODS: Thirty-one children (8.23+/-13.92
      months) with CHD who underwent CTA were enrolled. Images were reconstructed using
      SAFIRE (strength 5) and ADMIRE (strength 5). Objective image qualities
      (attenuation, noise) were measured in the great vessels and heart chambers. Two
      radiologists independently calculated the contrast-to-noise ratio (CNR) by
      measuring the intensity and noise of the myocardial walls. Subjective noise,
      diagnostic confidence, and sharpness at the level prior to the first branch of
      the main pulmonary artery were also graded by the two radiologists independently.
      RESULTS: The objective image noise of ADMIRE was significantly lower than that of
      SAFIRE in the right atrium, right ventricle, and myocardial wall (p<0.05);
      however, there were no significant differences observed in the attenuations among
      the four chambers and great vessels, except in the pulmonary arteries (p>0.05).
      The mean CNR values were 21.56+/-10.80 for ADMIRE and 18.21+/-6.98 for SAFIRE,
      which were significantly different (p<0.05). In addition, the diagnostic
      confidence of ADMIRE was significantly lower than that of SAFIRE (p<0.05), while
      the subjective image noise and sharpness of ADMIRE were not significantly
      different (p>0.05). CONCLUSION: CTA using ADMIRE was superior to SAFIRE when
      comparing the objective and subjective image quality in children with CHD.

PMID- 28764857
TI  - Despite or Due to the Cultural Revolution: The Development of Chinese Science,
      Technology, and Medicine in the 1960s and 1970s.

PMID- 28764858
TI  - M2b macrophages reduce early reperfusion injury after myocardial ischemia in
      mice: A predominant role of inhibiting apoptosis via A20.
AB  - BACKGROUND: Monocytes or macrophages have been assessed as potential therapeutics
      to ameliorate myocardial ischemic diseases, but the results have been
      controversial. As regulatory macrophages, M2b macrophages could have enhanced
      protective effects. We tested the hypothesis that transplantation of M2b
      macrophages could ameliorate myocardial ischemia/reperfusion (I/R) injury. The
      potential mechanisms involved in it were investigated. METHODS: M2b macrophages
      were polarized by lipopolysaccharide (LPS) and the immune complex (IC) from bone
      marrow-derived macrophages (BMDMs) of C57BL/6 mice. They were identified based on
      surface marker expression and cytokine production. Myocardial I/R injury models
      were established with the same strain of mice. Once the ischemic area was
      identified, either 1*105 M2b macrophages (MT group) or the same volume of normal
      saline (CK group) was injected into the ischemic zone. Mice in the sham operation
      (SO) group underwent the operation without ligation of the coronary artery.
      RESULTS: We found a significant decrease in serum cardiac troponin I (cTnI)
      level, the infarct area, apoptosis index, and nuclear factor-kappaB (NF-kappaB)
      signaling activation in the MT group after 2h of reperfusion; the changes were
      induced by I/R. In addition, the injury resulted in significantly up-regulated
      expression of A20 and continued to be improved by the transplanted M2b
      macrophages. CONCLUSIONS: The administration of M2b macrophages significantly
      attenuated myocardial I/R injury. A20 may be part of the protective mechanism
      through limiting NF-kappaB signaling-mediated apoptosis.

PMID- 28764860
TI  - CRISPRing the Regulatory Genome, the Challenge Ahead.
AB  - CRISPR saturation mutagenesis has the potential to dissect the functional
      landscape of noncoding regions, but is highly susceptible to false discovery and
      misinterpretation. As recently published, Canver et al. have now taken the first
      steps towards addressing these issues by increasing screening resolution and
      analyzing the effects of off targets on hit calling.

PMID- 28764859
TI  - Modeling 3D-CSIA data: Carbon, chlorine, and hydrogen isotope fractionation
      during reductive dechlorination of TCE to ethene.
AB  - Reactive transport modeling of multi-element, compound-specific isotope analysis
      (CSIA) data has great potential to quantify sequential microbial reductive
      dechlorination (SRD) and alternative pathways such as oxidation, in support of
      remediation of chlorinated solvents in groundwater. As a key step towards this
      goal, a model was developed that simulates simultaneous carbon, chlorine, and
      hydrogen isotope fractionation during SRD of trichloroethene, via cis-1,2
      dichloroethene (and trans-DCE as minor pathway), and vinyl chloride to ethene,
      following Monod kinetics. A simple correction term for individual
      isotope/isotopologue rates avoided multi-element isotopologue modeling. The model
      was successfully validated with data from a mixed culture Dehalococcoides
      microcosm. Simulation of Cl-CSIA required incorporation of secondary kinetic
      isotope effects (SKIEs). Assuming a limited degree of intramolecular
      heterogeneity of delta37Cl in TCE decreased the magnitudes of SKIEs required at
      the non-reacting Cl positions, without compromising the goodness of model fit,
      whereas a good fit of a model involving intramolecular CCl bond competition
      required an unlikely degree of intramolecular heterogeneity. Simulation of H-CSIA
      required SKIEs in H atoms originally present in the reacting compounds,
      especially for TCE, together with imprints of strongly depleted delta2H during
      protonation in the products. Scenario modeling illustrates the potential of H
      CSIA for source apportionment.

PMID- 28764861
TI  - Silencing of metallothionein 1A gene in melanoma.
AB  - BACKGROUND: When a CpG island (CGI; a dense cluster of CpGs) located in the 5'
      region of a gene is methylated, its transcription is suppressed. Tumorigenesis of
      melanoma is associated with trace elements. Metallothionein 1A is closely
      associated with the metabolism of trace elements. However, little is known about
      the metallothionein 1A gene (MT1A) in melanoma. OBJECTIVE: The purpose is to
      reveal the methylation and expression status of MT1A in melanoma. METHODS:
      Quantitative real-time methylation-specific PCR (RT-MSP) and bisulfite sequencing
      were performed to examine MT1A methylation status. Quantitative real-time reverse
      transcription-PCR (RT-PCR) was performed to examine MT1A expression. RESULTS:
      Some melanoma cell lines exhibited high methylation levels of the CGI located in
      the 5' region of MT1A (5' MT1A CGI) with suppression of MT1A. Other melanoma cell
      lines and normal cultured melanocytes exhibited low methylation levels of 5' MT1A
      CGI with expression of MT1A. Treatment with a demethylating agent resulted in
      transcriptional induction of MT1A in the melanoma cell lines SK-MEL-5 and G-361
      with high methylation levels prior to treatment. The methylation levels of 5'
      MT1A CGI ranged widely from 0.0% to 91.4% in 21 clinical melanoma samples but
      showed a narrow, low range from 0.0% to 6.4% in 23 clinical melanocytic nevus
      samples. Data of bisulfite sequencing was generally compatible with those of RT
      MSP. The methylation levels ranged according to the types of melanoma (Kruskal
      Wallis test, P=0.047). CONCLUSION: MT1A is aberrantly silenced by DNA methylation
      of 5' MT1A CGI in melanoma.

PMID- 28764862
TI  - Ferulic acid promotes osteogenesis of bone marrow-derived mesenchymal stem cells
      by inhibiting microRNA-340 to induce beta-catenin expression through hypoxia.
AB  - Osteogenic differentiation is regulated through multiple signaling networks that
      may include responses to hypoxia. Antioxidant ferulic acid (FA) can promote
      hypoxia signaling by inducing hypoxic-induced factor (HIF). However, whether FA
      could affect osteogenesis has not been explored. We examined human bone marrow
      derived mesenchymal stem cell (MSC) following FA treatment. The expression of
      beta-catenin was measured, and candidate microRNAs that target beta-catenin were
      studied. The involvement of hypoxia was investigated in miR-340-5p that contains
      hypoxia response elements (HRE) in the promoter region. Further, the osteogenic
      potential of FA-treated MSC was assessed by alkaline phosphatase (ALP) activity
      and alizarin red staining assays. Osteoblast marker gene expressions were also
      compared between controls and FA-treated cells. FA induced beta-catenin
      expression in MSC. This effect is likely mediated through a derepression of beta
      catenin 3'-UTR inhibition by miR-340-5p. HIF-1alpha, which suppressed miR-340-5p
      promoter activation through HRE motifs, was induced by FA. The induction of beta
      catenin signaling by FA was consistent with an enhancement in osteogenesis of FA
      treated MSC, which could be attenuated by miR-340-5p overexpression. Analysis of
      the signaling networks induced by FA reveals that hypoxia may promote the
      osteogenic program in mesenchymal stem cells via a novel microRNA pathway.

PMID- 28764863
TI  - Cellular expression, in-vitro and in-vivo confirmation of GAEC1 oncogenic
      properties in colon cancer.
AB  - GAEC1 (Gene amplified in esophageal cancer 1) alterations have oncogenic
      properties in oesophageal squamous cell carcinomas and frequent amplifications of
      the gene were noted in colorectal adenocarcinomas. However, the subcellular
      localization and expression of GAEC1 at the protein level have never been
      reported in human cancer cells. The present study aimed to investigate whether
      GAEC1 is differentially expressed in different stages of colon cancer and to
      elucidate its underlying cellular and molecular mechanism in colon cancer
      progression. We found differential expression of GAEC1 protein and mRNA in
      different pathological stages of colon cancer cells (SW480-Stage II, SW48-Stage
      III and HCT116-Stage IV) when compared to non-neoplastic colon cells (FHC cells)
      by immunocytochemistry, immunofluorescence, western blot analysis and real-time
      polymerase chain reaction. GAEC1 protein was predominantly expressed in the
      cytoplasm of colon cancer cells (SW480, SW48, and HCT116) and in the nucleus of
      non-neoplastic colon epithelial cells (FHC cells). The transient knockdown of
      GAEC1 using siRNA induced apoptosis in SW480 and SW48 cells, which was associated
      with G2/M phase arrest and decreased expression of bcl-2 and K-ras proteins and
      increased expression of p53. In addition, down-regulation of GAEC1 significantly
      inhibited (p<0.05) cell proliferation, reduced migration capacity and decreased
      clonogenic potentiality of colon cancer cells (SW480 and SW48 cells).
      Furthermore, a xenotransplantation model showed that stable knockdown of GAEC1
      using shRNA constructs in colon cancer cells fully suppressed xenograft tumour
      growth in mice. Collectively, the expression analysis, in vitro and in vivo data
      indicated that GAEC1 is differentially expressed in cancer cells and act as an
      oncogene in colon cancer progression.

PMID- 28764864
TI  - Accurate Measurement of Left Ventricular Outflow Tract Diameter: Comment on the
      Updated Recommendations for the Echocardiographic Assessment of Aortic Valve
      Stenosis.

PMID- 28764865
TI  - Rumen Microbiome, Probiotics, and Fermentation Additives.
AB  - Fermentation of a variety of feedstuffs by the ruminal microbiome is the
      distinctive feature of the ruminant digestive tract. The host derives energy and
      nutrients from microbiome activity; these organisms are essential to survival.
      Advances in DNA sequencing and bioinformatics have redefined the rumen microbial
      community. Current research seeks to connect our understanding of the rumen
      microbiome with nutritional strategies in ruminant livestock systems and their
      associated digestive disorders. These efforts align with a growing number of
      products designed to improve ruminal fermentation to benefit the overall
      efficiency of ruminant livestock production and health.

PMID- 28764866
TI  - Experimental assessment of the effects of moisture on loggerhead sea turtle
      hatchling sex ratios.
AB  - Many reptiles have temperature-dependent sex determination (TSD). Sex
      determination in marine turtles is described by a cool-male, warm-female pattern.
      Nest sand temperature strongly influences sea turtle embryo development and sex
      differentiation. Yet, variation in hatchling sex ratios is explained only
      partially by nest temperature and can be predicted only at the warmest and
      coolest temperatures. Hence, other factors during development influence sex
      determination. Rainfall is a common environmental variable that may impact
      development and sex determination. We experimentally evaluated bias in sex ratio
      production associated with nest moisture. Conditions tested in surrogate nests
      were sand moisture in combination with (i) very restricted evaporation, (ii)
      moderate evaporation (allowing evaporative cooling), and (iii) evaporative
      cooling plus cooling from rain-temperature water. We collected eggs from 32
      unique loggerhead (Caretta caretta L.) turtle clutches, distributed them among
      the three different conditions, and incubated the eggs until they hatched. All
      hatchlings were raised for several months and sex was verified laparoscopically
      to establish sex ratios for each treatment. The nests were expected to produce
      50:50 sex ratios or a moderate female bias (~70%) based on incubation
      temperatures. All experimental treatments produced high male bias (87-96%). These
      results support the hypothesis that moisture impacts sex ratios through
      evaporation and rainfall-based cooling. High male bias was observed in nests with
      and without restricted evaporative cooling and no direct cooling due to watering
      as well as those nests hydrated via cool (rainwater temperature) water. High
      moisture conditions may produce males through thermal or other mechanisms,
      highlighting the importance of examining other nest environmental factors on sex
      determination.

PMID- 28764867
TI  - Effect of tobacco smoking on frontal cortical thickness development: A
      longitudinal study in a mixed cohort of ADHD-affected and -unaffected youth.
AB  - Smoking rates are particularly high during adolescence and young adulthood, when
      the brain is still undergoing significant developmental changes. Cross-sectional
      studies have revealed altered brain structure in smokers, such as thinner frontal
      cortical areas. Attention-deficit/hyperactivity disorder (ADHD) increases the
      risk of becoming nicotine-dependent, and has also been associated with
      abnormalities in frontal gray matter structure. The present study examines the
      relationships between smoking, cortical thickness and ADHD symptoms in a
      longitudinal design that compares adolescent and young adult smokers (n=44; 35
      ADHD-affected) and non-smokers (n=45; 32 ADHD-affected) on frontal cortical
      thickness. Average frontal cortical thickness was estimated through structural
      magnetic resonance imaging (MRI) at two time points (mean ages 17.7 and 21.1
      years), on average 3.4 years apart. Smokers had a 2.6% thinner frontal cortex
      than non-smokers and this difference was not explained by ADHD or other
      confounding factors. The rate of cortical thinning across the 3.4-year MRI
      measurement interval was similar in the total group of smokers compared to non
      smokers. However, speeded thinning did occur in smokers who had started regular
      smoking more recently, in between the two measurements. These novel regular
      smokers did not differ significantly from the non-smokers at baseline. This
      suggests that the thinner frontal cortex was not a predisposing factor but rather
      a consequence of smoking. Although smokers had more ADHD symptoms overall,
      smoking did not influence the developmental course of ADHD symptoms.

PMID- 28764869
TI  - Intelligent computational model for classification of sub-Golgi protein using
      oversampling and fisher feature selection methods.
AB  - Golgi is one of the core proteins of a cell, constitutes in both plants and
      animals, which is involved in protein synthesis. Golgi is responsible for
      receiving and processing the macromolecules and trafficking of newly processed
      protein to its intended destination. Dysfunction in Golgi protein is expected to
      cause many neurodegenerative and inherited diseases that may be cured well if
      they are detected effectively and timely. Golgi protein is categorized into two
      parts cis-Golgi and trans-Golgi. The identification of Golgi protein via direct
      method is very hard due to limited available recognized structures. Therefore,
      the researchers divert their attention toward the sequences from structures.
      However, owing to technological advancement, exploration of huge amount of
      sequences was reported in the databases. So recognition of large amount of
      unprocessed data using conventional methods is very difficult. Therefore, the
      concept of intelligence was incorporated with computational model. Intelligence
      based computational model obtained reasonable results, but the gap of improvement
      is still under consideration. In this regard, an intelligent automatic
      recognition model is developed in order to enhance the true classification rate
      of sub-Golgi proteins. In this approach, discrete and evolutionary feature
      extraction methods are applied on the benchmark Golgi protein datasets to excerpt
      salient, propound and variant numerical descriptors. After that, an oversampling
      technique Syntactic Minority over Sampling Technique is employed to balance the
      data. Hybrid spaces are also generated with combination of these feature spaces.
      Further, Fisher feature selection method is utilized to reduce the extra noisy
      and redundant features from feature vector. Finally, k-nearest neighbor algorithm
      is used as learning hypothesis. Three distinct cross validation tests are used to
      examine the stability and efficiency of the proposed model. The predicted
      outcomes of proposed model are better than the existing models in the literature
      so far. Finally, it is anticipated that the proposed model will provide the
      foundation to pharmaceutical industry in drug design and research community to
      innovate new ideas in the area of computational biology and bioinformatics.

PMID- 28764868
TI  - Modeling new immunoregulatory therapeutics as antimicrobial alternatives for
      treating Clostridium difficile infection.
AB  - The current treatment paradigm in Clostridium difficile infection is the
      administration of antibiotics contributing to the high rates of recurrent
      infections. Recent alternative strategies, such as fecal microbiome
      transplantation and anti-toxin antibodies, have shown similar efficacy in the
      treatment of C. difficile associated disease (CDAD). However, barriers exist for
      either treatment or other novel treatments to displace antibiotics as the
      standard of care. To aid in the comparison of these and future treatments in
      CDAD, we developed an in silico pipeline to predict clinical efficacy with
      nonclinical results. The pipeline combines an ordinary differential equation
      (ODE)-based model, describing the immunological and microbial interactions in the
      gastrointestinal (GI) mucosa, with machine learning algorithms to translate
      simulated output quantities (i.e. time of clearance, quantity of commensal
      bacteria, T cell ratios) into clinical predictions based on prior preclinical,
      translational and clinical trial data. As a use case, we compare the efficacy of
      lanthionine synthetase C-like 2 (LANCL2), a novel immunoregulatory target with
      promising efficacy in inflammatory bowel disease (IBD), activation with
      antibiotics, fecal microbiome transplantation and anti-toxin antibodies in the
      treatment of CDAD. We further validate the potential of LANCL2 pathway
      activation, in a mouse model of C. difficile infection in which it displays an
      ability to decrease weight loss and inflammatory cell types while protecting
      against mortality. The computational pipeline can serve as an important resource
      in the development of new treatment modalities.

PMID- 28764870
TI  - Heart murmur detection based on wavelet transformation and a synergy between
      artificial neural network and modified neighbor annealing methods.
AB  - Early recognition of heart disease plays a vital role in saving lives. Heart
      murmurs are one of the common heart problems. In this study, Artificial Neural
      Network (ANN) is trained with Modified Neighbor Annealing (MNA) to classify heart
      cycles into normal and murmur classes. Heart cycles are separated from heart
      sounds using wavelet transformer. The network inputs are features extracted from
      individual heart cycles, and two classification outputs. Classification accuracy
      of the proposed model is compared with five multilayer perceptron trained with
      Levenberg-Marquardt, Extreme-learning-machine, back-propagation, simulated
      annealing, and neighbor-annealing algorithms. It is also compared with a Self
      Organizing Map (SOM) ANN. The proposed model is trained and tested using real
      heart sounds available in the Pascal database to show the applicability of the
      proposed scheme. Also, a device to record real heart sounds has been developed
      and used for comparison purposes too. Based on the results of this study, MNA can
      be used to produce considerable results as a heart cycle classifier.

PMID- 28764871
TI  - Subcellular localization prediction of apoptosis proteins based on evolutionary
      information and support vector machine.
AB  - OBJECTIVES: In this paper, a high-quality sequence encoding scheme is proposed
      for predicting subcellular location of apoptosis proteins. METHODS: In the
      proposed methodology, the novel evolutionary-conservative information is
      introduced to represent protein sequences. Meanwhile, based on the proportion of
      golden section in mathematics, position-specific scoring matrix (PSSM) is divided
      into several blocks. Then, these features are predicted by support vector machine
      (SVM) and the predictive capability of proposed method is implemented by
      jackknife test RESULTS: The results show that the golden section method is better
      than no segmentation method. The overall accuracy for ZD98 and CL317 is 98.98%
      and 91.11%, respectively, which indicates that our method can play a
      complimentary role to the existing methods in the relevant areas. CONCLUSIONS:
      The proposed feature representation is powerful and the prediction accuracy will
      be improved greatly, which denotes our method provides the state-of-the-art
      performance for predicting subcellular location of apoptosis proteins.

PMID- 28764872
TI  - Integration of data mining classification techniques and ensemble learning to
      identify risk factors and diagnose ovarian cancer recurrence.
AB  - Ovarian cancer is the second leading cause of deaths among gynecologic cancers in
      the world. Approximately 90% of women with ovarian cancer reported having
      symptoms long before a diagnosis was made. Literature shows that recurrence
      should be predicted with regard to their personal risk factors and the clinical
      symptoms of this devastating cancer. In this study, ensemble learning and five
      data mining approaches, including support vector machine (SVM), C5.0, extreme
      learning machine (ELM), multivariate adaptive regression splines (MARS), and
      random forest (RF), were integrated to rank the importance of risk factors and
      diagnose the recurrence of ovarian cancer. The medical records and pathologic
      status were extracted from the Chung Shan Medical University Hospital Tumor
      Registry. Experimental results illustrated that the integrated C5.0 model is a
      superior approach in predicting the recurrence of ovarian cancer. Moreover, the
      classification accuracies of C5.0, ELM, MARS, RF, and SVM indeed increased after
      using the selected important risk factors as predictors. Our findings suggest
      that The International Federation of Gynecology and Obstetrics (FIGO), Pathologic
      M, Age, and Pathologic T were the four most critical risk factors for ovarian
      cancer recurrence. In summary, the above information can support the important
      influence of personality and clinical symptom representations on all phases of
      guide interventions, with the complexities of multiple symptoms associated with
      ovarian cancer in all phases of the recurrent trajectory.

PMID- 28764873
TI  - Automatic detection of surgical haemorrhage using computer vision.
AB  - BACKGROUND AND OBJECTIVES: On occasions, a surgical intervention can be
      associated with serious, potentially life-threatening complications. One of these
      complications is a haemorrhage during the operation, an unsolved issue that could
      delay the intervention or even cause the patient's death. On laparoscopic surgery
      this complication is even more dangerous, due to the limited vision and mobility
      imposed by the minimally invasive techniques. METHODS: In this paper it is
      described a computer vision algorithm designed to analyse the images captured by
      a laparoscopic camera, classifying the pixels of each frame in blood pixels and
      background pixels and finally detecting a massive haemorrhage. The pixel
      classification is carried out by comparing the parameter B/R and G/R of the RGB
      space colour of each pixel with a threshold obtained using the global average of
      the whole frame of these parameters. The detection of and starting haemorrhage is
      achieved by analysing the variation of the previous parameters and the amount of
      pixel blood classified. RESULTS: When classifying in vitro images, the proposed
      algorithm obtains accuracy over 96%, but during the analysis of an in vivo images
      obtained from real operations, the results worsen slightly due to poor
      illumination, visual interferences or sudden moves of the camera, obtaining
      accuracy over 88%. The detection of haemorrhages directly depends of the correct
      classification of blood pixels, so the analysis achieves an accuracy of 78%.
      CONCLUSIONS: The proposed algorithm turns out to be a good starting point for an
      automatic detection of blood and bleeding in the surgical environment which can
      be applied to enhance the surgeon vision, for example showing the last frame
      previous to a massive haemorrhage where the incision could be seen using
      augmented reality capabilities.

PMID- 28764874
TI  - Machine learning based identification of protein-protein interactions using
      derived features of physiochemical properties and evolutionary profiles.
AB  - Proteins are the central constitute of a cell or biological system. Proteins
      execute their functions by interacting with other molecules such as RNA, DNA and
      other proteins. The major functionality of protein-protein interactions (PPIs) is
      the execution of biochemical activities in living species. Therefore, an accurate
      identification of PPIs becomes a challenging and demanding task for investigators
      from last few decades. Various traditional and computational methods have been
      applied but they have not achieved quite encouraging results. In order to extend
      the concept of computational model by incorporating intelligent, contemporary
      machine learning algorithms have been utilized for identification of PPIs. In
      this prediction model, protein sequences are expressed by using two distinct
      feature extraction methods namely: physiochemical properties of amino acids and
      evolutionary profiles method position specific scoring matrix (PSSM). Jackknife
      test and numerous performance parameters namely: specificity, recall, accuracy,
      MCC, precision, and F-measure were employed to compute the predictive quality of
      proposed model. After empirical analysis, it is determined that the proposed
      prediction model yielded encouraging predictive outcomes compared to existing
      state-of-the-art models. This achievement is ascribed with PSSM because it has
      clearly discerned a motif of PPIs. It is realized that the proposed prediction
      model will lead to be a practical and very useful tool for research community.

PMID- 28764875
TI  - The Nursing Home Pneumonia Risk Index: A Simple, Valid MDS-Based Method of
      Identifying 6-Month Risk for Pneumonia and Mortality.
AB  - BACKGROUND: Pneumonia is the leading infectious cause of hospitalization and
      death for nursing home (NH) residents; however, diagnosis is often delayed
      because classic signs of infection are not present. We sought to identify NH
      residents at high risk for pneumonia, to identify persons to target for more
      intensive surveillance and preventive measures. METHODS: Based on a literature
      review, we identified key risk factors for pneumonia and compiled them for use as
      prediction tool, limiting risk factors to those available on the Minimum Data Set
      (MDS). Next, we tested the tool's ability to predict 6-month pneumonia incidence
      and mortality rates in a sample of 674 residents from 7 NHs, evaluating it both
      as a continuous and a dichotomous variable, and applying both logistic regression
      and survival analysis to calculate estimates. RESULTS: NH Pneumonia Risk Index
      scores ranged from -1 to 6, with a mean of 2.1, a median of 2, and a mode of 2.
      For the outcome of pneumonia, a 1-point increase in the index was associated with
      a risk odds ratio of 1.26 (P = .038) or a hazard ratio of 1.24 (P = .037); using
      it as a dichotomous variable (<=2 vs >=3), the corresponding figures were a risk
      odds ratio of 1.78 (P = .045) and a hazard ratio of 1.82 (P = .025). For the
      outcome of mortality, a 1-point increase in the NH Pneumonia Risk Index was
      associated with a risk odds ratio of 1.58 (P = .002) and a hazard ratio of 1.45
      (P = .013); using the index as a dichotomous variable, the corresponding figures
      were a risk odds ratio of 3.71 (P < .001) and a hazard ratio of 3.29 (P = .001).
      CONCLUSIONS: The NH Pneumonia Risk Index can be used by NH staff to identify
      residents for whom to apply especially intensive preventive measures and
      surveillance. Because of its strong association with mortality, the index may
      also be valuable in care planning and discussion of advance directives.

PMID- 28764877
TI  - Conversion of finished leather waste incorporated with plant fibers into value
      added consumer products - An effort to minimize solid waste in Ethiopia.
AB  - Presently, the leftovers from leather product industries are discarded as waste
      in Ethiopia. The objective of the present study was therefore, to prepare
      composite sheets by incorporating various plant fibers like enset (Ensete
      ventricosum), hibiscus (Hibiscus cannabinus), jute (Corchorus trilocularis L.),
      palm (Phoenix dactylifera) and sisal (Agave sisal) in various proportions into
      the leather waste. Resin binder (RB) and natural rubber latex (NRL) were used as
      binding agents for the preparation of the composite sheets. The composite sheets
      prepared were characterized for their physicochemical properties (tensile
      strength, elongation at break, stitch tear strength, water absorption, water
      desorption and flexing strength). Composite sheets prepared using RB having 10%
      hibiscus, 20% palm and 40% sisal fibers showed better mechanical properties than
      their respective controls. In composite sheets prepared using NRL having 30% jute
      fiber exhibited better mechanical properties than its control. Most of the plant
      fibers used in this study played a role in increasing the performance of the
      sheets. However, as seen from the results, the contribution of these plant fibers
      on performance of the composite sheets prepared is dependent on the ratio used
      and the nature of binder. The SEM studies have exhibited the composite nature of
      the sheets and FTIR studies have shown the functional groups of collagen protein,
      cellulose and binders. The prepared sheets were used as raw materials for
      preparation of items like stiff hand bags, ladies' purse, keychain, chappal
      upper, wallet, wall cover, mouse pad and other interior decorating products. By
      preparing such value added products, we can reduce solid waste; minimize
      environmental pollution and thereby securing environmental sustainability.

PMID- 28764876
TI  - Determinants of Potentially Inappropriate Medication Use in Long-Term and Acute
      Care Settings: A Systematic Review.
AB  - BACKGROUND: Potentially inappropriate medications (PIMs) are widely used in
      institutionalized older adults, yet the key determinants that drive their use are
      incompletely characterized. METHODS: We systematically searched published
      literature within MEDLINE and Embase from January 1998 to March 2017. We searched
      for studies conducted in the United States that described determinants of PIM use
      in adults >=60 years of age in a nursing home or residential care facility, in
      the emergency department (ED), or in the hospital. Paired reviewers independently
      screened abstracts and full-text articles, assessed quality, and extracted data.
      RESULTS: Among 30 included articles, 12 examined PIM use in the nursing home or
      residential care settings, 4 in the ED, 12 in acute care hospitals, and 2 across
      settings. The Beers criteria were most frequently used to identify PIM use, which
      ranged from 3.6% to 92.0%. Across all settings, the most common determinants of
      PIM use were medication burden and geographic region. In the nursing home, the
      most common additional determinants were younger age, and diagnoses of depression
      or diabetes. In both the ED and hospital, patients receiving care in the West,
      Midwest, and South, relative to the Northeast, were at greater risk of receiving
      a PIM. Very few studies examined clinician determinants of PIM use; geriatricians
      used fewer PIMs in the hospital than other clinicians. CONCLUSIONS: Among older
      adults, those who are on many medications are at increased risk for PIM use
      across multiple settings. We propose that careful testing of interventions that
      target modifiable determinants are indicated to assess their impact on PIM use.

PMID- 28764878
TI  - Median nerve mobilization techniques in the treatment of carpal tunnel syndrome:
      A systematic review.
AB  - STUDY DESIGN: Systematic review. INTRODUCTION: Median nerve mobilization is one
      of the interventions used in the treatment of carpal tunnel syndrome (CTS).
      However, it is uncertain how many types of mobilization techniques are described
      in the current literature or the relative effectiveness of these techniques in
      treating CTS. PURPOSE OF THE STUDY: The aim of this review was to describe the
      types and effectiveness of median nerve mobilization techniques studied in the
      CTS literature. METHODS: Electronic searches of 5 databases and manual searches
      of references lists located randomized controlled trials studies published
      between 2000 and April 2015. Quality appraisal for each study was conducted using
      the Standard Quality Assessment Criteria for Evaluating Primary Research Papers
      from a Variety of Fields by 2 independent reviewers. RESULTS: Nine randomized
      controlled trial studies describing various median nerve mobilization techniques
      used in the treatment of CTS were included. All studies were rated as of
      "adequate", "good", or "strong" quality for the Standard Quality Assessment
      Criteria. Three techniques of median nerve mobilization were described. Treatment
      outcomes included measures of electrodiagnostic testing, functional performance,
      pain, physical examination, sensation, and strength. Standardized mean
      differences for the treatment outcomes ranged from very small to large (0.05
      1.71). CONCLUSION: The findings are inconclusive regarding the effectiveness of
      each mobilization technique due to methodological limitations in the current body
      of research. Therefore, there is a clear need for high-quality controlled studies
      to examine various approaches to median nerve mobilization techniques in the
      treatment of CTS. LEVEL OF EVIDENCE: 2a.

PMID- 28764879
TI  - Influence of design features of tibial stems in total knee arthroplasty on tibial
      bone remodeling behaviors.
AB  - In total knee arthroplasty, the optimal length and material of tibial stem remain
      controversial. This study aimed to evaluate influences of lengths and materials
      of cementless stems on tibial remodeling behaviors. Three groups of lengths were
      investigated (i.e., 110, 60, and 30 mm), and four materials (i.e., titanium,
      flexible 'iso-elastic' material, and two functionally graded materials [FGMs])
      were selected for each group. FGM is a kind of material whose composition
      gradually varies in space. In this study, the compositions of two FGMs were Ti
      and hydroxyapatite (FGM I), and Ti and bioglass (FGM II), respectively. Tibial
      models were incorporated with finite element analysis to simulate bone
      remodeling. Distributions of bone mineral density, von Mises stress, and
      interface shear stress were obtained. For the length, the long stem produced more
      serious stress shielding and stress concentration than the short stem, but it
      could provide better mechanical stability. For the material, FGM I could reduce
      stress shielding and stress concentration and reduce the risk of loosening.
      Compared with the length, the material had a pronounced effect on remodeling.
      This study provided theoretical basis for optimal design of stem to improve
      service life of tibial components and to reduce pain of patients.

PMID- 28764880
TI  - Risks and Challenges of Surgery for Aortic Prosthetic Valve Endocarditis.
AB  - BACKGROUND: Prosthetic valve endocarditis is the most severe form of infective
      endocarditis. This study assessed the risks and challenges of surgery for aortic
      prosthetic valve endocarditis. METHODS: In total, 116 consecutive patients (98
      males, age 65.2+/-12.7years), who underwent redo-surgery for active aortic
      prosthetic valve endocarditis between 2000 and 2014, were reviewed. Cox
      regression analysis was used to identify factors for aortic root destructions as
      well as for morbidity and mortality. Median follow-up was 3.8 years (0-13.9
      years). RESULTS: Aortic root destructions (42 limited and 29 multiple lesions)
      were associated with early prosthetic valve endocarditis and delayed diagnosis
      (>=14 d), but not with mortality. There were 16 (13.8%) early (<=30 d) and 32
      (27.6%) late (>30 days) deaths. Survival at 1, 5, and 10 years was 72+/-4.3%,
      56+/-5.4%, and 46+/-6.4%, respectively. The cumulative incidence of death,
      reinfection, and reoperation was 19.0% at 30days and 36.2% at 1year. Delayed
      diagnosis, concomitant procedures, and EuroSCORE II >20% were predictors for
      early mortality and need for mechanical circulatory support, age >70years, and
      critical preoperative state were predictors for late mortality. In their absence,
      survival at 10 years was 70+/-8.4%. Reinfections and reoperations occurred more
      frequently if >=1 risk factor for endocarditis and aortic root destructions were
      present. At 10 years, freedom from reinfection and reoperation was 89+/-4.2% and
      91+/-4.0%. CONCLUSIONS: The risks of death, reinfection, and reoperation are
      significant within the first year after surgery for aortic prosthetic valve
      endocarditis. Early diagnosis and aortic root destructions are the most important
      challenges, but advanced age, critical preoperative state, and the need for
      mechanical circulatory support determine long-term survival.

PMID- 28764881
TI  - Dosimetric impact of intrafraction changes in MR-guided high-dose-rate (HDR)
      brachytherapy for prostate cancer.
AB  - PURPOSE: To assess changes in implant and treatment volumes through the course of
      a prostate high-dose-rate brachytherapy procedure and their impact on plan
      quality metrics. METHODS AND MATERIALS: Sixteen MRI-guided high-dose-rate
      procedures included a post-treatment MR (ptMR) immediately after treatment
      delivery (135 min between MR scans). Target and organs at risk (OARs) were
      contoured, and catheters were reconstructed. The delivered treatment plan was
      applied to the ptMR image set. Volumes and dosimetric parameters in the ptMR were
      evaluated and compared with the delivered plan using a paired two-tailed t-test
      with p < 0.05 considered statistically significant. RESULTS: An average increase
      of 8.9% in prostate volume was observed for whole-gland treatments, resulting in
      reduction in coverage for both prostate and planning target volume, reflected in
      decreased V100 (mean 3.3% and 4.6%, respectively, p < 0.05), and D90 (mean 7.1%
      and 7.6%, respectively, of prescription dose, p < 0.05). There was no significant
      change in doses to OARs. For partial-gland treatments, there was an increase in
      planning target volume (9.1%), resulting in reduced coverage and D90 (mean 3.6%
      and 12.4%, respectively, p < 0.05). A decrease in D0.5cc for bladder (3%, p <
      0.05) was observed, with no significant changes in dose to other OARs.
      CONCLUSIONS: Volumetric changes were observed during the time between planning MR
      and ptMR. Nonetheless, treatment plans for both whole- and partial-gland
      therapies remained clinically acceptable. These results apply to clinical
      settings in which patients remain in the same position and under anesthesia
      during the entire treatment process.

PMID- 28764882
TI  - Accuracy and variability of high-dose-rate prostate brachytherapy needle tip
      localization using live two-dimensional and sagittally reconstructed three
      dimensional ultrasound.
AB  - PURPOSE: To measure the accuracy and variability of manual high-dose-rate (HDR)
      prostate brachytherapy (BT) needle tip localization using sagittally
      reconstructed three-dimensional (3D) transrectal ultrasound (TRUS) augmented with
      live two-dimensional (2D) sagittal TRUS. METHODS AND MATERIALS: Ten prostate
      cancer patients underwent HDR-BT during which the sagittally assisted sagittally
      reconstructed (SASR) segmentation technique was completed in parallel with
      commercially available sagittally assisted axially reconstructed (SAAR) TRUS for
      comparison. The SASR technique makes use of live 2D ultrasound intraoperatively
      and allows needle tip updates using the final 3D image in the absence of image
      artifacts. These updates were repeated offline twice by two separate users.
      Needle end-length measurements were used to calculate insertion depth errors
      (IDEs) for each technique. RESULTS: Images of 147 needles were analyzed. For the
      SASR technique, both users were confident in tip positions on the final 3D image
      within 3 mm for 52% of needles, so these tip positions were updated. For the
      remaining 48% of needles, the tip positions from the live 2D images were used.
      This SASR technique enabled the localization of all needles with IDEs within +/-3
      mm for 84% of needles and IDE range of [-6.2 mm, 5.9 mm], compared with 57% and [
      8.1 mm, 7.7 mm] when using the commercially available SAAR technique.
      CONCLUSIONS: The SASR technique mitigates the impact of 3D TRUS image artifacts
      on HDR-BT needle tip localization by incorporating live 2D sagittal TRUS
      intraoperatively and provides a statistically significant reduction in IDE
      variance compared with the routine SAAR technique.

PMID- 28764883
TI  - Involvement of GABAA receptors in the regulation of social preference and
      emotional behaviors by oxytocin in the central amygdala of female mandarin voles.
AB  - The central nucleus of the amygdala (CeA) is the main output of the amygdala and
      plays an important role in behavioral and neuroendocrine responses to stress.
      Receptors for the neuropeptide oxytocin (OT) and GABAA are found in high
      concentration in the CeA. The mechanisms underlying regulation of CeA OT in
      emotional and social behavior remain unclear. In this study we evaluated the
      effects of intra-CeA OT administration of different doses (0.1, 1 and 10ng/side),
      OT receptor antagonist (OTR-A) (1, 10 and 100ng/side) and OT plus OTR-A on social
      and emotional behavior using a social preference paradigm, open field test and
      elevated plus maze test in female monogamous mandarin voles (Microtus
      mandarinus). We then examined whether different doses of the GABAA receptor
      antagonist bicuculline (5, 10 and 100ng/side) affected the behavioral changes
      induced by intra-CeA microinjection of OT (1ng/side). We found that
      administration of OT to the CeA increased social preference, central area
      investigation times in the open field test, and visits, transitions and time
      spent in the open arms in the elevated plus maze test; all responses were dose
      dependent. Administration of OT plus OTR-A to the CeA produced no effects.
      Administration of bicuculline in combination with OT to the CeA decreased social
      preference, central area investigation times in the open field test, and visits,
      transitions and time spent in the open arms of the elevated plus maze test. These
      data suggest that OT in the CeA facilitates sociality and reduces levels of
      anxiety by interacting with local GABAA receptors.

PMID- 28764884
TI  - Corrigendum to "Serial mechanism in transposed letter effects: A developmental
      study" [J. Exp. Child Psychol. 161 (2017) 46-62].

PMID- 28764885
TI  - Plasma oxalate in relation to eGFR in patients with primary hyperoxaluria,
      enteric hyperoxaluria and urinary stone disease.
AB  - BACKGROUND: Since plasma oxalate (POx) concentrations increase at lower
      glomerular filtration rate (GFR) levels, even among those without enteric (EH) or
      primary hyperoxaluria (PH), the appropriate thresholds for considering a disorder
      of oxalate metabolism are poorly defined. The current study was completed to
      establish relationships between POx, GFR, and urine oxalate excretion (UOx) among
      patients with PH, EH, and routine urinary stone disease (USD). METHODS: The most
      recent POx measurement on all Mayo Clinic patients between 2005 and 2015 were
      electronically pulled from the Lab Information System together with the closest
      serum creatinine within 14days and 24h urine study within 60days. After exclusion
      of patients not in steady state at the time of blood draw, 270 patients were
      available for study. Records were reviewed for clinical diagnoses to categorize
      patients as PH, EH, or USD. Waste plasma for Pox was also obtained from controls
      without USD undergoing clinical GFR testing. RESULTS: In all 3 groups POx
      increased as eGFR fell. For any given eGFR, POx was highest in the PH group and
      lowest in the USD and control groups (p<0.0001). POx was also influenced by UOx
      excretion (reflecting total body oxalate burden, absorption from diet and
      endogenous production). Generalized estimating equations of POx vs eGFR revealed
      higher average POx levels in PH compared to EH,USD or control, and for EH
      compared to USD or control. GEE prediction models were created that use POx, UOx,
      age, and serum creatinine to estimate the probability of a PH diagnosis.
      CONCLUSIONS: New models were developed to help interpret POx when considering PH
      in clinical practice even when it was not previously suspected and/or eGFR is
      reduced.

PMID- 28764886
TI  - Are the thiol/disulfide redox status and HDL cholesterol levels associated with
      pulmonary embolism?: Thiol/disulfide redox status in pulmonary embolism.

PMID- 28764887
TI  - Disease-free survival is not a surrogate endpoint for overall survival in
      adjuvant trials of pancreatic cancer: a systematic review of randomized trials.
AB  - BACKGROUND: Adjuvant chemotherapy (CT) is the standard of care for patients with
      resected pancreatic cancer (PC). Overall survival (OS) has traditionally
      represented the primary endpoint in randomized trials assessing adjuvant
      therapies for PC. The aim of this study was to assess if disease-free survival
      (DFS) was an adequate surrogate endpoint for OS in randomized trials of adjuvant
      therapy in PC. METHODS: A systematic literature search was conducted in PubMed,
      Web of Science, SCOPUS and Embase, Cochrane Library and the World Health
      Organization International Clinical Trials Registry Platform up to February 2nd,
      2017. Surrogacy of DFS with OS was assessed between endpoints and OS through the
      Spearman rank correlation coefficient, and between the treatment effects on the
      endpoints using the squared correlation R2. RESULTS: A total of 12 eligible
      randomized trials that enrolled 4,888 patients where identified for the final
      analysis. Correlation of DFS with OS was weak at the individual level (Spearman
      rank correlation coefficient = 0.31) and moderate at the trial level (R2 = 0.44).
      CONCLUSIONS: DFS does not represent an appropriate surrogate for OS in randomized
      trials of adjuvant therapy for resected PC. Hence, OS should remain the primary
      endpoint of future trials evaluating new agents in postsurgical setting.

PMID- 28764888
TI  - Baseline Factors Affecting Changes in Diabetic Retinopathy Severity Scale Score
      After Intravitreal Aflibercept or Laser for Diabetic Macular Edema: Post Hoc
      Analyses from VISTA and VIVID.
AB  - PURPOSE: To evaluate whether select baseline systemic and ocular factors
      influence >=2-step improvement in the Diabetic Retinopathy Severity Scale (DRSS)
      score at week 100 in VISTA and VIVID. DESIGN: Post hoc analysis of 2 similarly
      designed phase 3 trials, VISTA and VIVID. PARTICIPANTS: Total of 456 patients
      with center-involved diabetic macular edema (DME). METHODS: VISTA and VIVID
      randomized 872 DME patients to receive intravitreal aflibercept injection (IAI) 2
      mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or
      macular laser photocoagulation. This post hoc analysis evaluated the influence of
      select baseline factors on >=2-step DRSS score improvement by logistic regression
      in an integrated VISTA and VIVID dataset using observed cases (n = 456) with
      patients in each treatment group divided into tertiles based on each
      characteristic. MAIN OUTCOME MEASURES: Proportion of patients with >=2-step
      improvement in DRSS score from baseline at week 100 by age, duration of diabetes,
      hemoglobin A1c (HbA1c), body mass index (BMI), best-corrected visual acuity
      (BCVA), central subfield thickness (CST), and DRSS score. RESULTS: At week 100,
      10.1%, 34.3%, and 37.6% of patients in the laser, 2q4, and 2q8 groups experienced
      a >=2-step DRSS score improvement, respectively. Age, duration of diabetes,
      HbA1c, BMI, BCVA, and CST had no impact on the ability to achieve >=2-step
      improvement in DRSS score. Initial DRSS score was the only factor significantly
      associated with >=2-step DRSS score improvement in all treatment groups at weeks
      24, 52, 76, and 100. Relatively higher proportions of IAI-treated patients with
      worse BCVA or thicker CST experienced >=2-step DRSS score improvement compared
      with those with better BCVA or thinner CST, respectively, but these associations
      were not statistically significant. CONCLUSION: A strong association was present
      between baseline DRSS score and >=2-step DRSS score improvement at week 100 for
      DME patients in VISTA and VIVID.

PMID- 28764889
TI  - Can Home Monitoring Allow Earlier Detection of Rapid Visual Field Progression in
      Glaucoma?
AB  - PURPOSE: Recent developments in electronic technology are making it possible to
      home monitor the sensitivity of the central visual field using portable devices.
      We used simulations to investigate whether the higher test frequency afforded by
      home monitoring improves the early detection of rapid visual field loss in
      glaucoma and how any benefits might be affected by imperfect compliance or
      increased variability in the home-monitoring test. DESIGN: Computer simulation,
      with parameter selection confirmed with a cohort study. PARTICIPANTS: A total of
      43 patients with treated glaucoma (both open-angle and closed-angle), ocular
      hypertension or glaucoma suspects (mean age, 71 years; range, 37-89 years), were
      followed in the cohort study. METHODS: We simulated series (n = 100 000) of
      visual fields for patients with stable glaucoma and patients with progressing
      glaucoma for 2 in-clinic (yearly and 6-monthly) and 3 home-monitoring (monthly,
      fortnightly, and weekly) schedules, each running over a 5-year period. Various
      percentages of home-monitored fields were omitted at random to simulate reduced
      compliance, and the variability of the home monitored fields also was
      manipulated. We used previously published variability characteristics for
      perimetry and confirmed their appropriateness for a home-monitoring device by
      measuring the device's retest variability at 2 months in a cohort of 43 patients.
      The criterion for flagging progression in our simulation was a significant slope
      of the ordinary least squares regression of a simulated patient's mean deviation
      (MD) data. MAIN OUTCOME MEASURES: The sensitivity for identifying rapid visual
      field loss (-2 decibels [dB]/year loss of MD). RESULTS: Although a sensitivity of
      0.8 for rapid field loss was achieved after 2.5 years of 6-monthly testing in the
      clinic, weekly home monitoring achieved this by 0.9 years despite moderate test
      compliance of 63%. The improved performance of weekly home monitoring over 6
      monthly clinical testing was retained even when home monitoring was assumed to
      produce more variable test results or be associated with low patient compliance.
      CONCLUSIONS: Detecting rapid visual field progression may be improved using a
      home-monitoring strategy, even when compliance is imperfect. The cost-benefit of
      such an approach is yet to be demonstrated, however.

PMID- 28764890
TI  - The impact of a retail prescription synchronization program on medication
      adherence.
AB  - OBJECTIVES: To understand the impact of prescription synchronization, offered
      through the ScriptSync(r) program at CVS pharmacies nationwide, on adherence and
      reducing visits to the pharmacy. DESIGN: Cohort study, conducted between March
      26, 2015, and December 18, 2015. Program enrollment occurred in August 2015, with
      a 120-day baseline period preceding enrollment and a 120-day follow-up period.
      SETTING AND PARTICIPANTS: CVS retail community pharmacies across the United
      States. CVS Pharmacy patients voluntarily enrolling in the prescription
      synchronization program at CVS retail community pharmacies across the United
      States who filled 3 or more eligible prescriptions before program enrollment. The
      study included 126,597 patients who enrolled in the program and 81,355 patients
      who enrolled after the study enrollment period. OUTCOME MEASURES: Adherence was
      defined as the medication possession ratio. The average number of pharmacy visits
      per month was a second outcome measure. RESULTS: Exposed patients had a 7.5
      percentage point adherence improvement (from 79.6% to 87.1%), compared with a 2.8
      percentage point improvement among the unexposed (from 78.1% to 80.9%) for a
      benefit of 4.7 percentage points (P < 0.0001). Among patients with adherence
      opportunities, the net impact on adherence was 10.6% (P < 0.0001). The program
      resulted in 0.17 fewer visits per month (P < 0.0001). CONCLUSION: Offering
      prescription refill synchronization at a large national retail pharmacy chain
      resulted in improved adherence and fewer visits to the pharmacy in the 4 months
      following ScriptSync enrollment. Prescription refill synchronization programs
      should be considered in the care of patients with multiple comorbidities.

PMID- 28764891
TI  - 2-methoxyethylacrylate modified polysulfone membrane and its blood compatibility.
AB  - Hydrophilic material 2-methoxyethylacrylate (MEA) was grafted onto polysulfone
      (PSF) membrane via Michael addition reaction. The 1H nuclear magnetic resonance
      (1H NMR), Attenuated total reflectance-Fourier transform infrared spectroscope
      (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) characterization of the
      modified membrane proved that MEA had been successfully grafted onto PSF membrane
      surface. The water contact angle of the membrane surface was tested. The results
      showed that the water contact angle changed from 76 degrees  to 59.5 degrees ,
      which means that the hydrophilicity of the modified membrane was improved. A
      series of blood compatibility tests including bovine serum protein adsorption,
      platelet adhesion, prothrombin time (PT), partial thromboplastin time (APTT) and
      thrombin time (TT) were carried out on PSF membrane and the modified PSF membrane
      with highest grafted density of MEA. All of the results indicate that MEA plays
      an important role in improving the blood compatibility of PSF membrane.

PMID- 28764892
TI  - Expression and function of spineless orthologs correlate with distal
      deutocerebral appendage morphology across Arthropoda.
AB  - The deutocerebral (second) head segment is putatively homologous across
      Arthropoda, in spite of remarkable disparity of form and function of
      deutocerebral appendages. In Mandibulata this segment bears a pair of sensory
      antennae, whereas in Chelicerata the same segment bears a pair of feeding
      appendages called chelicerae. Part of the evidence for the homology of
      deutocerebral appendages is the conserved function of homothorax (hth), which has
      been shown to specify antennal or cheliceral fate in the absence of Hox
      signaling, in both mandibulate and chelicerate exemplars. However, the genetic
      basis for the morphological disparity of antenna and chelicera is not understood.
      To test whether downstream targets of hth have diverged in a lineage-specific
      manner, we examined the evolution of the function and expression of spineless
      (ss), which in two holometabolous insects is known to act as a hth target and
      distal antennal determinant. Toward expanding phylogenetic representation of gene
      expression data, here we show that strong expression of ss is observed in
      developing antennae of a hemimetabolous insect, a centipede, and an amphipod
      crustacean. By contrast, ss orthologs are not expressed throughout the cheliceral
      limb buds of spiders or harvestmen during developmental stages when appendage
      fate is specified. RNA interference-mediated knockdown of ss in Oncopeltus
      fasciatus, which bears a simple plesiomorphic antenna, resulted in homeotic
      distal antenna-to-leg transformation, comparable to data from holometabolous
      insect counterparts. Knockdown of hth in Oncopeltus fasciatus abrogated ss
      expression, suggesting conservation of upstream regulation. These data suggest
      that ss may be a flagellar (distal antennal) determinant more broadly, and that
      this function was acquired at the base of Mandibulata.

PMID- 28764893
TI  - Knockdown of microRNA-203 alleviates LPS-induced injury by targeting MCL-1 in
      C28/I2 chondrocytes.
AB  - Several microRNAs (miRs) are associated with osteoarthritis (OA) and are also
      functionally implicated in the pathogenesis of the disease. This study was aimed
      to investigate the potential roles of miR-203 in the development and progression
      of OA, as well as to illustrate the possible molecular mechanism. OA was
      simulated in human cartilage C28/I2 cells with treatments of lipopolysaccharide
      (LPS). LPS-induced cell injury was evaluated according to cell viability,
      apoptosis and release of pro-inflammatory cytokines. Expression of miR-203 after
      LPS treatment was assessed. Then, miR-203 was aberrantly expressed, followed by
      evaluation of LPS-induced cell injury. The target gene of miR-203 was virtually
      screened by bioinformatics method and verified by luciferase assay. Moreover, the
      potential associated signaling pathways were also investigated. Results showed
      that LPS induced decrease of cell viability and increases of cell apoptosis,
      release of inflammatory cytokines and expression of miR-203. LPS-induced
      alterations were aggravated by miR-203 overexpression but were alleviated by miR
      203 inhibition. Myeloid cell leukemia-1 (MCL-1) was hypothesized and subsequently
      verified to be a target of miR-203, and miR-203 inhibition affected C28/I2 cells
      through up-regulating MCL-1. In addition, LPS-induced down-regulations of key
      kinases as well as phosphorylated kinases were further down-regulated by miR-203
      overexpression but were abrogated by miR-203 inhibition. In conclusion, this
      study suggests that miR-203 suppression may inhibit the progression of OA by
      targeting MCL-1 and activating the Wnt/beta-Catenin and JAK/STAT signal pathways.

PMID- 28764894
TI  - Investigating empathy in interpreter-mediated simulated consultations: An
      explorative study.
AB  - OBJECTIVE: To explore i) the ways in which empathic communication is expressed in
      interpreter-mediated consultations; ii) the interpreter's effect on the
      expression of empathic communication. METHODS: We coded 9 video-recorded
      interpreter-mediated simulated consultations by using the Empathic Communication
      Coding System (ECCS) which we used for each interaction during interpreter
      mediated consultations. We compared patients' empathic opportunities and doctors'
      responses as expressed by the patients and doctors and as rendered by the
      interpreters. RESULTS: In 44 of the 70 empathic opportunities there was a match
      between the empathic opportunities as expressed by the patients and as rendered
      by the interpreters. In 26 of the 70 empathic opportunities, we identified 5
      shift categories (reduced emotion, omitted emotion, emotion transformed into
      challenge, increased challenge/progress, twisted challenge) in the interpreter's
      rendition to the doctor. These were accompanied by changes in the level of
      empathy and in the content of the doctors' empathic responses. CONCLUSION: The
      interpreters' renditions had an impact on the patients' empathic opportunities
      and on the doctors' empathic responses in one third of the coded interactions.
      PRACTICE IMPLICATIONS: Curricula with a focus on intercultural communication
      and/or empathy should consider the complexity of interpreter-mediated interaction
      and the interpreter's impact on the co-construction of empathy.

PMID- 28764895
TI  - Numeracy of multiple sclerosis patients: A comparison of patients from the
      PERCEPT study to a German probabilistic sample.
AB  - OBJECTIVE: A shared decision-making approach is suggested for multiple sclerosis
      (MS) patients. To properly evaluate benefits and risks of different treatment
      options accordingly, MS patients require sufficient numeracy - the ability to
      understand quantitative information. It is unknown whether MS affects numeracy.
      Therefore, we investigated whether patients' numeracy was impaired compared to a
      probabilistic national sample. METHODS: As part of the larger prospective,
      observational, multicenter study PERCEPT, we assessed numeracy for a clinical
      study sample of German MS patients (N=725) with a standard test and compared them
      to a German probabilistic sample (N=1001), controlling for age, sex, and
      education. Within patients, we assessed whether disease variables (disease
      duration, disability, annual relapse rate, cognitive impairment) predicted
      numeracy beyond these demographics. RESULTS: MS patients showed a comparable
      level of numeracy as the probabilistic national sample (68.9% vs. 68.5% correct
      answers, P=0.831). In both samples, numeracy was higher for men and the highly
      educated. Disease variables did not predict numeracy beyond demographics within
      patients, and predictability was generally low. CONCLUSION: This sample of MS
      patients understood quantitative information on the same level as the general
      population. PRACTICE IMPLICATIONS: There is no reason to withhold quantitative
      information from MS patients.

PMID- 28764896
TI  - The effect of visual and musical suspense on brain activation and memory during
      naturalistic viewing.
AB  - We tested the hypothesis that, during naturalistic viewing, moments of increasing
      narrative suspense narrow the scope of attentional focus. We also tested how
      changes in the emotional congruency of the music would affect brain responses to
      suspense, as well as subsequent memory for narrative events. In our study,
      participants viewed suspenseful film excerpts while brain activation was measured
      with functional magnetic resonance imaging. Results indicated that suspense
      produced a pattern of activation consistent with the attention-narrowing
      hypothesis. For example, we observed decreased activation in the anterior
      calcarine sulcus, which processes the visual periphery, and increased activity in
      nodes of the ventral attention network and decreased activity in nodes of the
      default mode network. Memory recall was more accurate for high suspense than low
      suspense moments, but did not differ by soundtrack congruency. These findings
      provide neural evidence that perceptual, attentional, and memory processes
      respond to suspense on a moment-by-moment basis.

PMID- 28764897
TI  - [Clinical characteristics of patients with atrial fibrillation treated with
      direct oral anticoagulants attended in primary care setting. The SILVER-AP
      study].
AB  - OBJECTIVE: To analyse the clinical characteristics and management of patients
      with non-valvular atrial fibrillation (NVAF) treated with direct oral
      anticoagulants (DOAC). DESIGN: Observational, cross-sectional and multicentre
      study. LOCATION: Autonomous Communities in which the general practitioner can
      prescribe DOAC (n=9). PARTICIPANTS: The study included a total of 790 patients on
      chronic treatment with anticoagulants, and on whom therapy was changed, as well
      as being currently on treatment with DOAC for at least for 3 months. MAIN
      MEASURES: A record was made of the sociodemographic and clinical management date.
      RESULTS: Mean age was 78.6+/-8.4 years, and 50.5% of patients were men. Mean
      CHADS2 score was 2.6+/-1.2, mean CHA2DS2-VASc score was 4.3+/-1.6, and the mean
      HAS-BLED score was 2.3+/-1.0. Mean duration of treatment with DOAC was 15.8+/
      12.5 months. Rivaroxaban was the DOAC most frequently prescribed (57.8%),
      followed by dabigatran (23.7%), and apixaban (18.5%). Of the patients receiving
      rivaroxaban, 70.2% were taking the dose of 20mg/daily. Of the patients receiving
      dabigatran, 41.7% were taking the dose of 150mg twice daily, and in the case of
      apixaban, 56.2% were taking the dose of 5mg twice daily. Satisfaction (ACTS
      Burdens scale 52.0+/-7.2 and ACTS Benefits scale 12.1+/-2.2), and therapeutic
      adherence (97.8% of patients took their medication regularly) with DOAC were
      high. CONCLUSIONS: Patients treated with DOAC in Spain have a high thromboembolic
      risk. A significant proportion of patients receive a lower dose of DOAC than that
      recommended according to their clinical profile. Satisfaction and medication
      adherence are high.

PMID- 28764898
TI  - 64-Year-Old Woman With Weakness and Fall.

PMID- 28764899
TI  - Clinical Features, Etiologic Factors, Associated Disorders, and Treatment of
      Palmoplantar Pustulosis: The Mayo Clinic Experience, 1996-2013.
AB  - OBJECTIVE: To further characterize clinical characteristics, etiologic factors,
      associated disorders, and treatment of palmoplantar pustulosis (PPP). PATIENTS
      AND METHODS: We conducted a retrospective review of patients with PPP at Mayo
      Clinic between January 1, 1996, and December 31, 2013. RESULTS: Of 215 patients
      with PPP identified, 179 (83%) were female, and the mean age at onset was 45.3
      years. Most patients (n=165, 77%) were current or former smokers. At diagnosis,
      15 patients (7%) had an anxiety diagnosis and 9 (4%) had an infection. Nineteen
      cases (9%) were drug induced. Comorbid conditions included thyroid disease in 18
      patients (8%), gluten sensitivity in 3 (1%), and type 2 diabetes mellitus in 21
      (10%). In all, 194 patients (90%) received topical corticosteroids, 55 (26%)
      received phototherapy, and 54 (25%) received systemic agents. CONCLUSION: More
      than three-fourths of the patients in this study had a history of smoking, which
      is considered a triggering or aggravating factor for PPP. Regarding comorbid
      conditions, gluten sensitivity and thyroid disease were found less frequently
      than previously reported in the literature. Treatment regimens and responses in
      this cohort varied considerably.

PMID- 28764900
TI  - Mitochondrial replacement therapy: born in the USA: the untold story of a
      conceptual breakthrough.

PMID- 28764901
TI  - Providers perspectives on self-regulation impact their use of responsive feeding
      practices in child care.
AB  - Supporting children's self-regulation in eating through caregivers' practice of
      responsive feeding is paramount to obesity prevention, and while much attention
      has been given to supporting children's self-regulation in eating through
      parents' responsive feeding practices in the home setting, little attention has
      been given to this issue in childcare settings. This qualitative study examines
      childcare providers' perspectives on using responsive feeding practices with
      young children (2-5years). Individual semi-structured interviews were conducted
      with providers until saturation was reached. Data was analyzed using thematic
      analysis. The final sample included 18 providers who were employed full-time in
      Head Start or state-licensed center-based childcare programs, cared for children
      (2-5y), and were directly responsible for serving meals and snacks. Providers
      were primarily (67%) employed in childcare programs that served children from low
      income families and received reimbursement for meals and snacks from the US
      Department of Agriculture's Child and Adult Care Food Program. Three factors
      emerged that shaped childcare providers' experiences using responsive feeding
      practices: the providers' perspectives about whether or not young children can
      self-regulate food intake, their understanding of Child and Adult Care Food
      Program (CACFP) portion size regulations, and the availability of food at the
      center where they worked. Future research should examine how childcare providers'
      understanding of children's ability to self-regulate their food intake, the
      appropriate use of the CACFP regulations in relationship to serving sizes, and
      having food available to offer seconds promotes providers' use of responsive
      feeding practices in center-based childcare programs and children's dietary
      behaviors.

PMID- 28764902
TI  - Experimental animal models of Parkinson's disease: A transition from assessing
      symptomatology to alpha-synuclein targeted disease modification.
AB  - With the understanding that alpha-synuclein plays a major role in the
      pathogenesis of Parkinson's disease (PD), novel animal models have been developed
      for conducting preclinical research in screening novel disease modifying
      therapies. Advancements in research techniques in alpha-synuclein targeted
      disease modification have utilised methods such as viral mediated expression of
      human alpha-synuclein, as well as the inoculation of pathogenic alpha-synuclein
      species from Lewy Bodies of PD patients, for accurately modelling progressive
      self-propagating neurodegeneration. In applying these cutting-edge research tools
      with sophisticated trial designs in preclinical drug trials, a useful platform
      has emerged for developing candidate agents with disease modifying actions,
      promising a greater chance of success for clinical translation. In this article,
      we describe the transition of well-established animal models of PD symptomatology
      to newly developed models of PD pathogenesis, with specific focus on methods of
      viral-mediated and inoculation of pathogenic alpha-synuclein, that aim to aid
      scientific translation of neuroprotective strategies.

PMID- 28764903
TI  - Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease.
AB  - In the translation of discoveries from the laboratory to the clinic, the track
      record in developing disease-modifying therapies in neurodegenerative disease is
      poor. A carefully designed development pipeline built from discoveries in both
      pre-clinical models and patient populations is necessary to optimize the chances
      for success. Genetic variation in the leucine-rich repeat kinase two gene (LRRK2)
      is linked to Parkinson disease (PD) susceptibility. Pathogenic mutations,
      particularly those in the LRRK2 GTPase (Roc) and COR domains, increase LRRK2
      kinase activities in cells and tissues. In some PD models, small molecule LRRK2
      kinase inhibitors that block these activities also provide neuroprotection.
      Herein, the genetic and biochemical evidence that supports the involvement of
      LRRK2 kinase activity in PD susceptibility is reviewed. Issues related to the
      definition of a therapeutic window for LRRK2 inhibition and the safety of chronic
      dosing are discussed. Finally, recommendations are given for a biomarker-guided
      initial entry of LRRK2 kinase inhibitors in PD patients. Four key areas must be
      considered for achieving neuroprotection with LRRK2 kinase inhibitors in PD: 1)
      identification of patient populations most likely to benefit from LRRK2 kinase
      inhibitors, 2) prioritization of superior LRRK2 small molecule inhibitors based
      on open disclosures of drug performance, 3) incorporation of biomarkers and
      empirical measures of LRRK2 kinase inhibition in clinical trials, and 4)
      utilization of appropriate efficacy measures guided in part by rigorous pre
      clinical modeling. Meticulous and rational development decisions can potentially
      prevent incredibly costly errors and provide the best chances for LRRK2
      inhibitors to slow the progression of PD.

PMID- 28764904
TI  - Photosensitized methyl paraben induces apoptosis via caspase dependent pathway
      under ambient UVB exposure in human skin cells.
AB  - Methyl paraben (MP), is a widely used preservative in pharmaceutical, food and
      cosmetic products. Its molecular mechanism under ambient ultraviolet radiation is
      not well understood. We investigated photosensitizing mechanism of MP under
      ambient UVB (0.6 mW/cm2) intensity. MP showed dose dependent decrease in cell
      viability of human keratinocyte cell line (HaCaT) by MTT and NRU assays. Study
      showed 40% reduction in antimicrobial activity of UVB irradiated MP through E.
      coli culture. Photosensitized MP (25 MUg/ml) significantly enhanced lipid
      peroxidation, intracellular ROS generation and disrupted mitochondrial membrane
      integrity. MP induced loss of lysosomal membrane integrity and endoplasmic
      reticulum (ER) mediated stress evident from Ca+2 release. Phototoxicity of MP
      showed nuclear fragmentation, phosphatidylserine translocation, 30% tail DNA and
      micronuclei formation. Study showed mitochondria mediated apoptosis via
      upregulation of Bax, Apaf-1, Cytochrome C and Caspase-3. Upregulation of Caspase
      12 (2 folds) specifically showed role of ER in apoptosis. Specific caspase
      inhibitor, Z-VAD-FMK showed involvement of caspase cascade pathway in apoptosis.
      Results indicate that photosensitive MP leads to oxidative stress mediated DNA
      damage and apoptosis through mitochondria and ER. MP causes deleterious effects
      and its long term exposure to human skin may promote skin diseases. Therefore, MP
      should be replaced by other photosafe preservatives for humans.

PMID- 28764906
TI  - Nurse contribution in the treatment of cystic fibrosis.

PMID- 28764905
TI  - Comparison of short- and long-term exposure effects of cruciferous and apiaceous
      vegetables on carcinogen metabolizing enzymes in Wistar rats.
AB  - Cruciferous and apiaceous vegetables may be chemopreventive due to their ability
      to modulate carcinogen-metabolizing enzymes but whether the effects on such
      enzymes are sustained over time is unknown. To examine the short- and long-term
      effects of the vegetables, rats were fed one of four diets for 7, 30, or 60 d:
      AIN-93G, CRU (21% cruciferous vegetables-fresh broccoli, green cabbage,
      watercress), API (9% apiaceous vegetables - fresh parsnips, celery), or API + CRU
      (10.5% CRU + 4.5% API). Although CRU increased activity and protein expression of
      cytochrome P450 (CYP) 1A1 and CYP1A2 after 7 d, only activity was sustained after
      30 and 60 d. There was a trend towards an interaction between the length of
      feeding period and CRU for CYP1A1 activity; activity increased with greater time
      of feeding. API increased CYP1A2 activity but decreased sulfotransferase 1A1
      activity after 7 d, although not at later times. Altogether, increased CYP1A
      activity by CRU was maintained with long term feeding while protein amount
      decreased, suggesting influence by mechanisms other than, or in addition to,
      transcriptional regulation. Thus, response patterns and interactions with length
      of feeding may differ, depending upon the types of vegetables and enzymes,
      requiring caution when interpreting the results of short-term feeding studies.

PMID- 28764907
TI  - Practical importance of the results derived from regression models: Contributions
      to Madera-Anaya et al.

PMID- 28764908
TI  - Neuroprotective effects of lentivirus-mediated cystathionine-beta-synthase
      overexpression against 6-OHDA-induced parkinson's disease rats.
AB  - Parkinson's disease (PD) is age-related neurodegenerative disorder by a
      progressive loss of dopaminergic(DA) neurons in the substantia nigra (SN) and
      striatum, which is at least partly associated with alpha-synuclein protein
      accumulation in these neurons. Hydrogen sulfide (H2S) plays an important role in
      the nervous system. Studies have shown that H2S has a protective effect on PD.
      However, as a kind of gas molecules, H2S is lively, volatile, and not conducive
      to scientific research and clinical application. Cystathionine-beta-synthase(CBS)
      is the main enzymes of synthesis of H2S in the brain. In order to examine the
      neuroprotective effects of CBS on PD, we detected the effects of CBS
      overexpression on 6-Hydroxydopamine (6-OHDA)-lesioned PD rats using lentivirus
      mediated gene transfection techniques. In the injured SN of 6-OHDA-induced PD
      rats, the CBS expression and the endogenous H2S level markedly decreased, while
      administration of lentivirus-mediated CBS overexpression increased the CBS
      expression and the endogenous H2S production.CBS overexpression dramatically
      reversed apomorphine-induced rotation of the 6-OHDA model rats, decreased the
      number of TUNEL-positive neurons and the loss of the nigral DA
      neurons,specifically inhibited 6-OHDA-induced oxidase stress injury, and down
      regulated the expression of alpha-synuclein(alpha-SYN) in the injured SN. NaHS
      (an H2S donor) had similar effects to CBS overexpression, while Amino
      oxyacetate(AOAA, a CBS inhibitor) had opposite effects on PD rats. In summary, we
      demonstrated that CBS overexpression was able to provide neuroprotective on PD
      rats and improving the expression of CBS may be a potential therapeutic method
      for PD.

PMID- 28764909
TI  - A novel PSEN1 (S230N) mutation causing early-onset Alzheimer's Disease associated
      with prosopagnosia, hoarding, and Parkinsonism.
AB  - We describe clinical and biomarker findings in an index patient with the onset of
      Alzheimer's disease (AD) symptoms at age 57 and a family history consistent with
      an autosomal dominant pattern of inheritance. She had the atypical early features
      of visual agnosia and prosopagnosia followed by hoarding behavior and
      Parkinsonism. Structural MRI revealed global atrophy that was most severe in the
      lateral temporal lobes and insular cortex bilaterally. CSF biomarker assessment
      showed Abeta42, p-tau181, and total tau levels consistent with AD. Genetic
      assessment revealed a novel mutation in the PSEN1 gene (S230N) in the index
      patient and her affected brother which was absent in her two clinically
      unaffected and AD-biomarker negative sisters. The serine residue at codon 230 in
      PSEN1 is highly conserved across species and in PSEN2, providing strong evidence
      for its pathogenicity in this family.

PMID- 28764910
TI  - Effect of total solids content on biohydrogen production and lactic acid
      accumulation during dark fermentation of organic waste biomass.
AB  - Production of biohydrogen and related metabolic by-products was investigated in
      Solid State Dark Fermentation (SSDF) of food waste (FW) and wheat straw (WS). The
      effect of the total solids (TS) content and H2 partial pressure (ppH2), two of
      the main operating factors of SSDF, were investigated. Batch tests with FW at 10,
      15, 20, 25 and 30% TS showed considerable effects of the TS on metabolites
      distribution. H2 production was strongly inhibited for TS contents higher than
      15% with a concomitant accumulation of lactic acid and a decrease in substrate
      conversion. Varying the ppH2 had no significant effect on the conversion products
      and overall degradation of FW and WS, suggesting that ppH2 was not the main
      limiting factor in SSDF. This study showed that the conversion of complex
      substrates by SSDF depends on the substrate type and is limited by the TS
      content.

PMID- 28764911
TI  - Cultural diffusion of Indo-Aryan languages into Bangladesh: A perspective from
      mitochondrial DNA.
AB  - Although both linguistic and historical studies indicated only a small group of
      Aryans had been involved into the diffusion of Indo-Aryan languages into
      Bangladesh, no genetic studies had been carried out to prove this notion. By
      studying mitochondrial DNA variants of 240 Bengali speakers in Bangladesh, among
      which 23 mitogenomes are completely sequenced, we found a high proportion of
      South Asian components in this group. By contrast, only a small proportion of
      lineages can be traced back to western Eurasia, which could be attributed to
      recent gene flow. Our results implied a cultural diffusion of the Indo-Aryan
      languages into Bangladesh.

PMID- 28764912
TI  - C-reactive protein and cardiovascular risk in bipolar disorder patients: A
      systematic review.
AB  - OBJECTIVES: New research is revealing a strong association between inflammatory
      markers with bipolar disorder (BD), potentially due to the high prevalence of
      cardiovascular disease and cardiovascular risk factors in BD. We aimed to
      synthesize the literature examining the association between the clinically most
      relevant inflammatory marker, C-reactive protein (CRP) and cardiovascular disease
      and cardiovascular risk factors in patients with BD. METHODS: MEDLINE, Embase and
      PsychInfo were systematically searched for all relevant English language articles
      published prior to April 2017. Articles were included if they examined the
      association between CRP and cardiovascular risk factors/disease in BD. RESULTS:
      Fifteen relevant articles were retrieved. Studies were mostly cross-sectional and
      heterogeneous in the cardiovascular risk factors investigated. Overall, elevated
      CRP was associated with increased risk of metabolic syndrome, elevated body mass
      index, higher waist circumference, and obesity. CRP was inconsistently associated
      with elevated fasting glucose, insulin levels, serum triglycerides, total
      cholesterol levels, and low high density lipoprotein (HDL) levels. Atypical
      antipsychotic use may mediate some of these effects. No study examined CRP's
      association with actual cardiovascular disease (e.g. coronary artery disease) in
      BD. CONCLUSIONS: In BD, CRP is associated with increases in several
      cardiovascular risk factors, suggesting that systemic inflammation could be a
      shared driving force for both outcomes of BD and cardiovascular risk. Further
      longitudinal research is needed in this area to verify causality, including an
      examination of actual cardiovascular disease. Non-pharmacological and
      pharmacological treatments with anti-inflammatory effects should also be
      investigated, particularly in patients with increased CRP, for their potential to
      reduce cardiovascular risk in BD.

PMID- 28764913
TI  - microRNA-124 targets glucocorticoid receptor and is involved in depression-like
      behaviors.
AB  - Dysregulation of microRNA (miRNA) has been shown to be involved in early
      observations of depression. MicroRNA-124-3p (miR-124) is the most abundant
      microRNA in the brain. Previous studies have shown that miR-124 plays a major
      role in depression. Here we showed that miR-124 directly targeted glucocorticoid
      receptor (GR) in HEK 293 cells. In addition, inhibition of miR-124 by its
      antagomir (2nmol/every two days) could reverse the decrease of sucrose preference
      and the increase of immobility time in mice exposed to chronic corticosterone
      (CORT, 40mg/kg) injection. Moreover, these effects on behavioral improvement were
      coupled to the activation of brain-derived neurotrophic factor (BDNF), TrkB, ERK,
      and CREB, as well as the induction of synaptogenesis and neuronal proliferation.
      Altogether, our study suggests that miR-124 can be served as a biomarker for
      depression and a novel target for drug development, and demonstrates that
      inhibition of miR-124 may be a strategy for treating depression by activating
      BDNF-TrkB signaling pathway in the hippocampus.

PMID- 28764914
TI  - Breaking down autophagy and the Ubiquitin Proteasome System.
AB  - Autophagy is an evolutionarily conserved catabolic process that is involved in
      cellular homeostasis and stress responses. Although basal levels of autophagy are
      essential for cellular homeostasis, dysregulated autophagy is linked to
      neurodegeneration. Recent studies using genetic or neurotoxin-based models of
      Parkinson's disease (PD) detect autophagy. We demonstrate that neurotoxins induce
      autophagy in dopaminergic neuronal cell line and primary cultured neurons. Based
      on previous reports, including ones from our laboratory, which show that elevated
      reactive oxygen species (ROS) and cytosolic calcium are implicated in
      dopaminergic neurodegeneration, we reasoned that these triggers may play critical
      roles in determining dysregulated autophagy. Similarly, we have demonstrated that
      ROS-mediated signals play an essential role in 6-hydroxydopamine (6-OHDA)-induced
      apoptosis, whereas MPP+ causes elevations in cytosolic calcium and calpain
      activation. By using these experimental models, we specifically address the
      question as to whether an increase in ROS or cytosolic calcium governs abnormal
      flux of autophagy as well as the ubiquitin proteasome system (UPS). So far, our
      data support a notion that ROS and cytosolic calcium act on a distinct flux of
      autophagy and the UPS. Our data also raise the possibility of interplay between
      autophagy and other cell death modes (e.g., caspase- or calpain-dependent cell
      death) during dopaminergic neurodegeneration.

PMID- 28764915
TI  - Cytotoxic oleanane triterpenoid saponins from Albizia julibrissin.
AB  - Bioassay-guided fractionation of the ethanolic extract of the stem bark of
      Albizia julibrissin led to the isolation of ten new oleanane-type triterpenoid
      saponins, julibrosides J37-J46 (1-10), along with six known analogues (11-16). In
      addition, 11 prosapogenins (17-27) were prepared by mild or strong alkaline
      hydrolysis of the total saponin. The structures of 1-27 were determined by
      spectroscopic and chemical means, and their cytotoxicities against four human
      cancer cell lines, BGC-823, A549, HCT-116, and HepG2 were evaluated. Compounds 5
      16 exhibited significant inhibitory activity with IC50 values ranging from 2.59
      to 9.30MUM, and 8 turned out to be the most active compound with all IC50 values
      <5MUM. A preliminary structure-activity relationship of these saponins clearly
      indicated that the outer monoterpenoid moiety (MT') is a crucial substituent for
      cytotoxicity, and the linkage sites of the MT' unit greatly influenced the
      activity. It could also be inferred that the existence of 16-OH of the aglycone
      almost has no effect on cytotoxicity and the N-acetyl-glucosamine moiety at C-3
      seems to enhance activity.

PMID- 28764916
TI  - Outcome of oscillating saw open osteotomy in two-stage lower extremity bone
      transport with monolateral frame.
AB  - INTRODUCTION: Bone transport techniques have been widely used to solve massive
      bone defects due to trauma, osteomyelitis or bone tumors. The technique of bone
      interruption to achieve better new bone formation is a subject of debate. Low
      energy osteotomy (LEO) techniques have been proposed as the gold standard. Some
      authors reject open osteotomy with an oscillating saw (OOS osteotomy), based on
      the danger of bone tissue thermal necrosis and periosteal damage. To date,
      however, there is no strong clinical evidence to discourage this high-energy
      (HEO) bone interruption technique. METHODS: The aim of this study was to
      determine outcomes in using OOS osteotomy in a series of patients, where
      monolateral-frame bone transport has been used to resolve segmental bone defects
      of the lower extremity. The minimum accepted follow-up was 1 year. The primary
      endpoints were radiographic evidence of regenerated bone quality (Li
      classification) and final outcome (Cattaneo clinical system assessment). Further,
      we analyzed associated complications, and compared results with other published
      series. We hypothesized that OOS osteotomy produces results no less favorable
      than those achieved with other, low-energy techniques. RESULTS: A total of 54
      patients, with an average bone defect of 8.58cm (CI95% 7.01-10.16), were enrolled
      in the study. In terms of regeneration quality, 84% of the regenerated segment
      shapes were associated with good outcomes; only 16% exhibited a shape
      (hypotrophic) predictive of a poor outcome. Regarding functional assessment,
      following the Cattaneo system, we found a total of 90% good or excellent results.
      Finally, the Bone Healing Index (BHI) in our series averaged 21.09 days per cm.
      The main complication observed was pin-track infection, occurring in 45% of the
      cases. CONCLUSION: According our data, the superiority of an LEO technique over
      HEO techniques is yet to be confirmed; it appears that any open osteotomy is
      effective, performed well and in a proper clinical setting, and that many factors
      other than choice of osteotomy technique must play important roles.

PMID- 28764917
TI  - Can the possibility of transverse iliosacral screw fixation for first sacral
      segment be predicted preoperatively? Results of a computational cadaveric study.
AB  - OBJECTIVES: The purpose of this study was to predict the possibility of
      transverse iliosacral (TIS) screw fixation into the first sacral segment (S1) and
      introduce practical anatomical variables using conventional computed tomography
      (CT) scans. MATERIALS AND METHODS: A total of 82 cadaveric sacra (42 males and 40
      females) were used for continuous 1.0-mm slice CT scans, which were imported into
      Mimics(r) software to produce a three-dimensional pelvis model. The anterior
      height (BH) and superior width (BW) of the elevated sacral segment was measured,
      followed by verification of the safe zone (SZS1 and SZS2) in a true lateral view.
      Their vertical (VDS1 and VDS2) and horizontal (HDS1 and HDS2) distances were
      measured. VDS1 less than 7mm was classified as impossible sacrum, since the
      transverse fixation of 7.0 mm-sized IS screw could not be done safely. RESULTS:
      Fourteen models (16.7%; six females, eight males) were assigned as the impossible
      sacrum. There was no statistical significance regarding gender (p=0.626) and
      height (p=0.419). The average values were as follows: BW, 31.4mm (SD 2.9); BH,
      16.7mm (SD 6.8); VDS1, 13.4mm (SD 6.1); HDS1, 22.5mm (SD 4.5); SZS1, 239.5mm2 (SD
      137.1); VDS2, 15.5mm (SD 3.0); HDS2, 18.3mm (SD 2.9); and SZS2, 221.1mm2 (SD
      68.5). Logistic regression analysis identified BH (p=0.001) and HDS1 (p=0.02) as
      the only statistically significant variables to predict the possibility. Receiver
      operating characteristic curve analysis established a cut-off value for BH and
      HDS1 of impossible sacrum of 20.6mm and 18.6mm, respectively. CONCLUSION: BH and
      HDS1 could be used to predict the possibility of TIS screw fixation. If the BH
      exceeds 20.6mm or HDS1 is less than 18.6mm, TIS screw fixation for S1 should not
      be undertaken because of narrowed SZ.

PMID- 28764918
TI  - Early weight loss after laparoscopic sleeve gastrectomy predicts midterm weight
      loss in morbidly obese Asians.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is a popular bariatric procedure
      in morbidly obese Asians. OBJECTIVES: To investigate the effect of initial weight
      loss on midterm weight maintenance and remission of co-morbidities after
      laparoscopic SG in morbidly obese Asians. SETTING: University Hospital,
      Singapore. METHODS: Data of patients who underwent laparoscopic SG were analyzed.
      Change in body mass index (BMI), percentage of total weight loss (%WL), and of
      excess weight loss (%EWL) was calculated and remission of obesity-related co
      morbidities was examined. Linear regression analysis was performed to determine
      the effect of initial weight loss on successful weight maintenance. Receiver
      operative characteristic curve analysis was used to define optimal cutoff values.
      RESULTS: Two hundred and seventy-two patients were included in this study. Mean
      preoperative weight and BMI were 115.4+/-25.5 kg and 42.5+/-8.0 kg/m2,
      respectively. Mean follow-up duration was 27.6+/-16.4 months. Successful weight
      loss of>50% EWL was achieved by 65.7%, 65.5%, and 50.8% of patients at 1, 2, and
      3 years, postoperatively. There was a significant correlation of %EWL at 3 months
      with %EWL up to 3 years (P<=.005). Receiver operative characteristic analysis
      showed initial EWL of 35% at 3 months best predicted successful weight loss at 1
      year (sensitivity 73.1%, specificity 81.4%). Patients achieving>35% EWL were
      significantly more likely to achieve remission of co-morbidities (P<=.005) at 1
      year after surgery. CONCLUSION: Early weight loss at 3 months predicts weight
      maintenance up to 3 years and remission of co-morbidities at 1 year after
      laparoscopic SG in Asians.

PMID- 28764919
TI  - Effects of Higher Quality of Care on Initiation of Long-term Dialysis in Patients
      With CKD and Diabetes.
AB  - BACKGROUND: The burden of diabetes-related chronic kidney disease (CKD) on
      individuals and society is increasing, shifting attention toward improving the
      quality of care for patients with CKD and diabetes. We assessed the quality of
      CKD care and its association with long-term dialysis, acute kidney injury (AKI),
      and death. STUDY DESIGN: Retrospective cohort study (2004-2011). SETTING &
      PARTICIPANTS: Adults in Taiwan with incident CKD enrolled in the Longitudinal
      Cohort of Diabetes Patients. PREDICTORS: 3 CKD-care quality indicators based on
      medical and pharmacy claims data were studied: prescription of renin-angiotensin
      system inhibitors, testing for proteinuria, and nutritional guidance. Each was
      examined individually, and all were summed into an overall quality score.
      OUTCOMES: The primary outcome was initiation of long-term dialysis therapy.
      Secondary outcomes were hospitalization due to AKI and death from any cause.
      MEASUREMENTS: Using instrumental variables related to the quality indicators to
      minimize both unmeasured and measured confounding, we fit a 2-stage residual
      inclusion model to estimate HRs and 95% CIs for each outcome. RESULTS: Among the
      63,260 patients enrolled, 43.9% were prescribed renin-angiotensin system
      inhibitors, 60.6% were tested for proteinuria, and 13.4% received nutritional
      guidance. During a median follow-up of 37.9 months, 1,471 patients started long
      term dialysis therapy, 2,739 patients were hospitalized due to AKI, and 4,407
      patients died. Higher overall quality scores were associated with lower hazards
      for long-term dialysis in instrumental variable analyses (HR of 0.62 [95% CI,
      0.40-0.98] per 1-point greater score) and hospitalization due to AKI (HR of 0.69
      [95% CI, 0.50-0.96] per 1-point greater score). The hazard for all-cause death
      was nonsignificantly lower (HR of 0.80 [95% CI, 0.62-1.03] per 1-point greater
      score). LIMITATIONS: Potential misclassification and uncontrolled confounding by
      indication. CONCLUSIONS: Our findings suggest potential opportunities to improve
      long-term outcomes among patients with diabetes and CKD by improving the quality
      of their CKD care.

PMID- 28764920
TI  - Patients' Experiences After CKD Diagnosis: A Meta-ethnographic Study and
      Systematic Review.
AB  - BACKGROUND: Chronic kidney disease (CKD) is often asymptomatic at first
      diagnosis, and awareness of CKD is low in the general population. Thus,
      individuals who are unexpectedly identified as having CKD may struggle to adjust
      to living with this diagnosis. This study aims to synthesize qualitative research
      exploring patients' views and experiences of a CKD diagnosis and how they adjust
      to it. STUDY DESIGN: Systematic review and meta-ethnography. SETTING &
      POPULATION: Adult patients with CKD stages 1 to 5. SEARCH STRATEGY & SOURCES:
      MEDLINE, PsycINFO, CINAHL, Embase, and Web of Science were searched from the
      earliest date available to November 2015. Qualitative studies were selected that
      explored patients' views and experiences of a CKD diagnosis and their adjustment.
      ANALYTICAL APPROACH: Meta-ethnography was adopted to synthesize the findings.
      RESULTS: 10 studies involving 596 patients with CKD from secondary-care settings
      were included. 7 key themes were identified: a challenging diagnosis, diverse
      beliefs about causation, anticipated concerns about progression, delaying disease
      progression, unmet informational needs, psychosocial impact of CKD, and
      adjustment to life with CKD. LIMITATIONS: Limited to views and experiences of
      participants in included studies, which were mostly conducted in high-income
      countries. Studies not written in English were excluded. Transferability of
      findings to other populations may be limited. CONCLUSIONS: This review highlights
      variation in patients' understanding of CKD, an overall lack of information on
      the trajectory of CKD, and a need for psychosocial support, especially in later
      stages, to help patients adjust to living with CKD. Future research that
      acknowledges CKD as a condition with diverse complicating morbidities and
      explores how patients' information and psychosocial needs vary according to
      severity and comorbid conditions would be beneficial. This will support delivery
      of easily understandable, timely, and targeted information about CKD, as well as
      practical advice about recommended lifestyle changes.

PMID- 28764922
TI  - Tissue-specific mineralization defects in the periodontium of the Hyp mouse model
      of X-linked hypophosphatemia.
AB  - X-linked hypophosphatemia (XLH) is a dento-osseous disorder caused by
      inactivating mutations in the PHEX gene, leading to renal phosphate wasting and
      hypophosphatemia, and impaired mineralization of bones and teeth. In the oral
      cavity, recent reports suggest a higher susceptibility of XLH patients to
      periodontitis, where patients present with impaired tooth cementum - a bone-like
      tissue involved in tooth attachment to the jaw bones and post-eruption tooth
      positioning - and a higher frequency of intrabony defects. In the present study,
      the pathobiology of alveolar bone and tooth cementum was investigated in the Hyp
      mouse, the murine analog of XLH. PHEX deficiency in XLH/Hyp dramatically alters
      the periodontal phenotype, with hypoplasia of tooth root cementum associated with
      a lack of periodontal ligament attachment and the presence of an immature
      apatitic mineral phase of all periodontal mineralized tissues. Challenging the
      Hyp periodontium in two surgical experimental models - ligature-induced
      periodontal breakdown and repair, and a model of tooth movement adaptation
      inducing cementum formation - we show that bone and cementum formation, and their
      healing, are altered. Bone and cementum mineralization appear similarly
      disturbed, where hypomineralized pericellular matrix surrounds cells, and where
      the protein osteopontin (OPN, a mineralization inhibitor) accumulates in a tissue
      specific manner, most notably in the perilacunar matrix surrounding osteocytes.
      Although the pathobiology is different between XLH/Hyp bone and cementum, our
      results show a major XLH phenotype in oral mineralized tissues consistent with
      variations in patient susceptibility to periodontal disorders.

PMID- 28764921
TI  - Early life bisphenol A exposure and neurobehavior at 8years of age: Identifying
      windows of heightened vulnerability.
AB  - BACKGROUND: Early life BPA exposure could affect neurobehavior, but few studies
      have investigated whether there are developmental periods when the fetus or child
      is more vulnerable to these potential effects. OBJECTIVES: We explored windows of
      vulnerability to BPA exposure in a multiethnic cohort of 228 mothers and their
      children from Cincinnati, Ohio. METHODS: We measured urinary BPA concentrations
      at up to two prenatal and six postnatal time points from the 2nd trimester of
      pregnancy until the child was age 8years. At age 8years, we administered the
      Behavioral Assessment System for Children-2 (BASC-2), Behavior Rating Inventory
      of Executive Function, and Wechsler Intelligence Scale for Children-IV. We
      estimated covariate-adjusted differences in composite scores from each instrument
      using a multiple informant model designed to identify heightened windows of
      vulnerability. RESULTS: Among all children, there was not strong evidence that
      the associations between BPA and neurobehavior varied by the timing of exposure
      (Visit x BPA p-values>=0.16). However, child sex modified the associations of
      repeated BPA measures with BASC-2 scores (Visit x Sex x BPA p-values=0.02-0.23).
      For example, each 10-fold increase in prenatal BPA was associated with more
      externalizing behaviors in girls (beta=6.2, 95% CI: 0.8, 11.6), but not boys
      (beta=-0.8, 95% CI: -5.0, 3.4). In contrast, a 10-fold increase in 8-year BPA was
      associated with more externalizing behaviors in boys (beta=3.9, 95% CI: 0.6,
      7.2), but not girls (beta=0.3, 95% CI: -3.5, 4.1). CONCLUSIONS: We found that sex
      dependent associations between BPA and child neurobehavior may depend on the
      timing of BPA exposure.

PMID- 28764923
TI  - Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with
      dengue severity and its functional effects.
AB  - Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the
      Americas, pose a global threat due to their rapid spread and difficulty
      controlling the vector. Extreme phenotypes are often observed, from asymptomatic
      to severe clinical manifestations, which are well-studied in dengue. Host
      variations are also important contributors to disease outcomes, and many case
      control studies have associated single nucleotide polymorphisms (SNPs) with
      severe dengue. Here, we found that the TC genotype and T-carriers for SNP
      rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated
      with severe dengue in a Northern Brazilian population (OR=2.75 and p-value=0.01,
      OR=2.11 and p-value=0.04, respectively). We also tested the functional effect of
      the CLEC5A protein and found that it is upregulated on the surface of human
      monocytes after in vitro dengue infection. CLEC5A was correlated with viral load
      inside the monocytes (Spearman r=0.55, p=0.008) and TNF production in culture
      supernatants (Spearman r=0.72, p=0.03). Analysis of mRNA in blood samples from
      DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA
      expression is correlated with TNF (r=0.67, p=0.0001) and other immune mediators.
      Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression
      compared to CC genotypes. However, in these cells, CLEC5A was not correlated with
      TNF production. In summary, we confirmed that CLEC5A is genetically associated
      with dengue severity outcome, playing a central role during the immune response
      triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is
      able to regulate signaling pathways after interactions between the dengue virus
      and CLEC5A receptors.

PMID- 28764924
TI  - Partial breast irradiation with interstitial multi-catheter high-dose-rate
      brachytherapy. Long-term results of a phase II prospective study.
AB  - PURPOSE: We report the long-term results of phase II prospective study with
      accelerated partial breast irradiation (APBI) using interstitial multi-catheter
      high-dose-rate brachytherapy. METHODS: 240 patients received APBI (4Gy, twice
      daily; total dose 32Gy). RESULTS: Median follow-up was 96months. Recurrences in
      the treated breast developed in 8 patients (3.3%) at a median of 73months after
      APBI. The 5- and 10-year cumulative incidences were respectively, 1.8% (95%CI:
      0.6-4.3) and 6.6% (95%CI: 2.7-12.9). Regional recurrences developed in 5 patients
      (2%) at a median of 28months and distant metastases in 8 (3.3%) at a median of
      32.5months. Breast cancer specific mortality occurred in 6 patients (2.5%) at a
      median of 60months. Acute toxicity developed in 71 (29.6%) patients (G1 in 60 and
      G2 in 11). Almost all were skin toxicity and hematomas. Late toxicity was
      observed in 90 patients (37.5%), G1 in 97 cases and G2 in 11. Some patients
      presented with more than one type of toxicity. Teleangectasia and fibrosis were
      the most common (48 and 44 cases respectively), followed by fat necrosis (in 18
      patients) Tamoxifen emerged as the only risk factor for breast fibrosis
      (p=0.007). Cosmetic results were judged by the physicians as excellent in 174
      (83.7%) patients, good in 25 (12%) fair in 8 (3.8%) and poor in 1 (0.5%); 174
      patients (83.7%) judged outcomes as excellent, 26 (12.4%) as good, 7 (3.4%) as
      fair and 1 (0.5%) as poor. Physician/patient agreement was good (weighted k-value
      0.72). CONCLUSIONS: APBI with interstitial multi-catheter brachytherapy was
      associated with good outcomes, low relapse and toxicity rates. Few events during
      this long-term follow-up preclude identifying specific features of patients at
      risk of relapse and illustrate the need for a large data-base.

PMID- 28764925
TI  - Profile of European proton and carbon ion therapy centers assessed by the EORTC
      facility questionnaire.
AB  - BACKGROUND: We performed a survey using the modified EORTC Facility questionnaire
      (pFQ) to evaluate the human, technical and organizational resources of particle
      centers in Europe. MATERIAL AND METHODS: The modified pFQ consisted of 235
      questions distributed in 11 sections accessible on line on an EORTC server.
      Fifteen centers from 8 countries completed the pFQ between May 2015 and December
      2015. RESULTS: The average number of patients treated per year and per particle
      center was 221 (range, 40-557). The majority (66.7%) of centers had pencil beam
      or raster scanning capability. Four (27%) centers were dedicated to eye treatment
      only. An increase in the patients-health professional FTE ratio was observed for
      eye tumor only centers when compared to other centers. All centers treated
      routinely chordomas/chondrosarcomas, brain tumors and sarcomas but rarely breast
      cancer. The majority of centers treated pediatric cases with particles. Only a
      minority of the queried institutions treated non-static targets. CONCLUSIONS: As
      the number of particle centers coming online will increase, the experience with
      this treatment modality will rise in Europe. Children can currently be treated in
      these facilities in a majority of cases. The majority of these centers provide
      state of the art particle beam therapy.

PMID- 28764926
TI  - Improving the prediction of overall survival for head and neck cancer patients
      using image biomarkers in combination with clinical parameters.
AB  - PURPOSE: To develop and validate prediction models of overall survival (OS) for
      head and neck cancer (HNC) patients based on image biomarkers (IBMs) of the
      primary tumor and positive lymph nodes (Ln) in combination with clinical
      parameters. MATERIAL AND METHODS: The study cohort was composed of 289
      nasopharyngeal cancer (NPC) patients from China and 298 HNC patients from the
      Netherlands. Multivariable Cox-regression analysis was performed to select
      clinical parameters from the NPC and HNC datasets, and IBMs from the NPC dataset.
      Final prediction models were based on both IBMs and clinical parameters. RESULTS:
      Multivariable Cox-regression analysis identified three independent IBMs (tumor
      Volume-density, Run Length Non-uniformity and Ln Major-axis-length). This IBM
      model showed a concordance(c)-index of 0.72 (95%CI: 0.65-0.79) for the NPC
      dataset, which performed reasonably with a c-index of 0.67 (95%CI: 0.62-0.72) in
      the external validation HNC dataset. When IBMs were added in clinical models, the
      c-index of the NPC and HNC datasets improved to 0.75 (95%CI: 0.68-0.82; p=0.019)
      and 0.75 (95%CI: 0.70-0.81; p<0.001), respectively. CONCLUSION: The addition of
      IBMs from the primary tumor and Ln improved the prognostic performance of the
      models containing clinical factors only. These combined models may improve pre
      treatment individualized prediction of OS for HNC patients.

PMID- 28764927
TI  - d-Tyrosyl-tRNA Deacylase: A New Function.
AB  - d-Aminoacyl-tRNA deacylase (DTD) hydrolyzes d-amino acids mistakenly attached to
      tRNAs and, thus, has been implicated in perpetuating protein homochirality. Fifty
      years after the discovery of DTD, it has now been shown that its function extends
      beyond 'chiral proofreading' because it also eliminates glycine that has been
      erroneously coupled to tRNAAla.

PMID- 28764928
TI  - Tissue engineering: Dentin - pulp complex regeneration approaches (A review).
AB  - Dental pulp is a highly specialized tissue that preserves teeth. It is important
      to maintain the capabilities of dental pulp before a pulpectomy by creating a
      local restoration of the dentin-pulp complex from residual dental pulp. The
      articles identified were selected by two reviewers based on entry and exit
      criteria. All relevant articles indexed in PubMed, Springer, Science Direct, and
      Scopus with no limitations from 1961 to 2016 were searched. Factors investigated
      in the selected articles included the following key words: Dentin-Pulp Complex,
      Regeneration, Tissue Engineering, Scaffold, Stem Cell, and Growth Factors. Of the
      233 abstracts retrieved, the papers which were selected had evaluated the
      clinical aspects of the application of dentin-pulp regeneration. Generally, this
      study has introduced a new approach to provoke the regeneration of the dentin
      pulp complex after a pulpectomy, so that exogenous growth factors and the
      scaffold are able to induce cells and blood vessels from the residual dental pulp
      in the tooth root canal. This study further presents a new strategy for local
      regeneration therapy of the dentin-pulp complex. This review summarizes the
      current knowledge of the potential beneficial effects derived from the
      interaction of dental materials with the dentin-pulp complex as well as potential
      future developments in this exciting field.

PMID- 28764929
TI  - Inhibition of Aurora Kinase A Induces Necroptosis in Pancreatic Carcinoma.
AB  - BACKGROUND & AIMS: Induction of nonapoptotic cell death could be an approach to
      eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies
      in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We
      screened 273 commercially available kinase inhibitors for cytotoxicity against a
      human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase
      inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2.03,
      CFPAC1, MiaPaCa2, BxPc3, and PANC02) and the HEK293 cell line, measuring loss of
      plasma membrane integrity, gain in cell volume, swollen organelles, and
      cytoplasmic vacuoles. We tested the effects of CCT137690 in colon formation
      assays, and the effects of the necroptosis (necrostatin-1 and necrosulfonamide),
      apoptosis, autophagy, and ferroptosis inhibitors. We derived cells from tumors
      that developed in Pdx1-Cre;K-RasG12D/+;p53R172H/+ (KPC) mice. Genes encoding
      proteins in cell death pathways were knocked out, knocked down, or expressed from
      transgenes in PDAC cell lines. Athymic nude or B6 mice were given subcutaneous
      injections of PDAC cells or tail-vein injections of KPC tumor cells. Mice were
      given CCT137690 (80 mg/kg) or vehicle and tumor growth was monitored; tumor
      tissues were collected and analyzed by immunohistochemistry. We compared gene
      expression levels between human pancreatic cancer tissues (n = 130) with patient
      survival times using the online R2 genomics analysis and visualization platform.
      RESULTS: CCT137690 induced necrosis-like death in PDAC cell lines and reduced
      colony formation; these effects required RIPK1, RIPK3, and MLKL, as well as
      inhibition of aurora kinase A (AURKA). AURKA interacted directly with RIPK1 and
      RIPK3 to reduce necrosome activation. AURKA-mediated phosphorylation of glycogen
      synthase kinase 3 beta (GSK3beta) at serine 9 inhibited activation of the RIPK3
      and MLKL necrosome. Mutations in AURKA (D274A) or GSK3beta (S9A), or
      pharmacologic inhibitors of RIPK1 signaling via RIPK3 and MLKL, reduced the
      cytotoxic activity of CCT137690 in PDAC cells. Oral administration of CCT137690
      induced necroptosis and immunogenic cell death in subcutaneous and orthotopic
      tumors in mice, and reduced tumor growth and tumor cell phosphorylation of AURKA
      and GSK3beta. CCT137690 increased survival times of mice with orthotopic KPC
      PDACs and reduced tumor growth, stroma, and metastasis. Increased expression of
      AURKA and GSK3beta mRNAs associated with shorter survival times of patients with
      pancreatic cancer. CONCLUSIONS: We identified the aurora kinase inhibitor
      CCT137690 as an agent that induces necrosis-like death in PDAC cells, via RIPK1,
      RIPK3, and MLKL. CCT137690 slowed growth of orthotopic tumors from PDAC cells in
      mice, and expression of AURKA and GSK3beta associate with patient survival times.
      AURKA might be targeted for treatment of pancreatic cancer.

PMID- 28764930
TI  - Association between educational attainment and amyloid deposition across the
      spectrum from normal cognition to dementia: neuroimaging evidence for protection
      and compensation.
AB  - The brain mechanisms underlying the effect of intellectual enrichment may evolve
      along the normal aging Alzheimer's disease (AD) cognitive spectrum and may
      include both protective and compensatory mechanisms. We assessed the association
      between early intellectual enrichment (education, years) and average cortical
      florbetapir standardized uptake value ratio as well as performed voxel-wise
      analyses in a total of 140 participants, including cognitively normal older
      adults, mild cognitive impairment (MCI), and AD patients. Higher education was
      associated with lower cortical florbetapir positron emission tomography
      (florbetapir-PET) uptake, notably in the frontal lobe in normal older adults, but
      with higher uptake in frontal, temporal, and parietal regions in MCI after
      controlling for global cognitive status. No association was found in AD. In MCI,
      we observed an increased fluorodeoxyglucose positron emission tomography (FDG
      PET) uptake with education within the regions of higher florbetapir-PET uptake,
      suggesting a compensatory increase. Early intellectual enrichment may be
      associated with protection and compensation for amyloid beta (Abeta) deposition
      later in life, before the onset of dementia. Previous investigations have been
      controversial as regard to the effects of intellectual enrichment variables on
      Abeta deposition; the present findings call for approaches aiming to evaluate
      mechanisms of resilience across disease stages.

PMID- 28764931
TI  - Acinetobacter pittii biofilm formation on inanimate surfaces after long-term
      desiccation.
AB  - BACKGROUND: The survival of pathogenic micro-organisms in the healthcare
      environment has a major role in nosocomial infections. Among the responsible
      mechanisms enabling nosocomial pathogens to persist with these stress conditions
      is their ability to resist desiccation and to form biofilms. AIM: To investigate
      the survival behaviour of Acinetobacter pittii isolates on inert surfaces and
      saline microcosms. METHODS: Five A. pittii clinical strains were spotted over
      white laboratory coat fragments, glass, and plastic surfaces, or inoculated into
      sterile saline and monitored at room temperature for a period of 43 days.
      FINDINGS: Although the permanence on solid surfaces negatively affected the
      culturability of the strains used, a fraction of stressed cells survived for at
      least the period of study. On average, A. pittii culturability was reduced by
      77.3%, 80.9%, and 68.1% in white coat, plastic, and glass surfaces, respectively.
      However, ~85.6% of the populations retain their culturability in saline solution.
      Culturability correlated with the presence of cells with an intact membrane, as
      demonstrated after live/dead staining. Supplementation of the culture medium with
      sodium pyruvate favoured the culturability of strains from all conditions; but,
      in general, A. pittii populations did not enter a viable but non-culturable
      state. CONCLUSION: After long-term desiccation, all A. pittii strains retained,
      or even increased, their ability to form biofilms after they had been fed with
      nutrient media. This suggests that A. pittii may recover easily from desiccation
      and may express adherence factors to infect new hosts after rehydration.

PMID- 28764932
TI  - Adeno-associated viral serotypes differentially transduce inhibitory neurons
      within the rat amygdala.
AB  - Recombinant adeno-associated viruses (AAV) are frequently used to make localized
      genetic manipulations within the rodent brain. It is accepted that the different
      viral serotypes possess differing affinities for particular cell types, but it is
      not clear how these properties affect their ability to transduce specific
      neuronal cell sub-types. Here, we examined ten AAV serotypes for their ability to
      transduce neurons within the rat basal and lateral nuclei of the amygdala (BLA)
      and the central nucleus of the amygdala (CeA). AAV2 based viral genomes designed
      to express either green fluorescent protein (GFP) from a glutamate decarboxylase
      (GAD65) promoter or the far-red fluorescent protein (E2-Crimson) from a phosphate
      activated glutaminase (PAG) promoter were created and pseudotyped as AAV2/1,
      AAV2/4, AAV2/5, AAV2/6, AAV2/7, AAV 2/8, AAV2/9, AAV2/rh10, AAV2/DJ and AAV2/DJ8.
      These viruses were infused into the BLA and CeA at equal titers and twenty-one
      days later tissue within the amygdala was examined for viral transduction
      efficiency. These serotypes transduced neurons with similar efficiency, except
      for AAV4 and AAV5, which exhibited significantly less efficient neuronal
      transduction. Notably, AAV4 and AAV5 possess the most divergent capsid protein
      sequences compared to the other commonly available serotypes. We found that the
      Gad65-GFP virus did not exclusively express GFP within inhibitory neurons, as
      assessed by fluorescent in situ hybridization (FISH), but when this virus was
      used to transduce CeA neurons, the majority of the neurons that expressed GFP
      were in fact inhibitory neurons and this was likely due to the fact that this
      nucleus contains a very high percentage of inhibitory neurons.

PMID- 28764933
TI  - Analysis of c-Fos induction in response to social interaction in male and female
      Fisher 344 rats.
AB  - Sex differences in the expression of social behavior are typically apparent in
      adolescent and adult rats. While the neurobiology underlying juvenile social play
      behavior has been well characterized, less is known about discrete brain regions
      involved in adult responsiveness to a same sex peer. Furthermore, whether adult
      males and females differ in their responsiveness to a social interaction in terms
      of neuronal activation indexed via immediate early gene (IEG) expression remains
      to be determined. Thus, the present study was designed to identify key sites
      relevant to the processing of sensory stimuli (generally) or social stimuli
      (specifically) after brief exposure to a same-sex social partner by assessing IEG
      expression. Four-month-old male and female Fisher (F) 344 rats (N=38; n=5
      8/group) were either left undisturbed in their home cage as controls (HCC),
      exposed to a testing context alone for 30min (CXT), or were placed in the context
      for 20min and then allowed to socially interact (SI) with a sex-matched
      conspecific for 10min. Females demonstrated greater levels of social behavior,
      relative to males. Analysis of c-Fos induction revealed that females exhibited
      greater c-Fos expression in the prefrontal cortex, regardless of condition. In
      many brain regions, induction was similar in the CXT and SI groups. However, in
      the bed nucleus of the stria terminalis (BNST), females exhibited greater c-Fos
      induction in response to the social interaction relative to their male
      counterparts, indicating a sex difference in responsivity to social stimuli.
      Taken together, these data suggest that the BNST is a sexually dimorphic region
      in terms of activation in response to social stimuli.

PMID- 28764935
TI  - Fractional anisotropy is a marker in early-stage spinal cord injury.
AB  - This study was designed to investigate whether fractional anisotropy (FA)
      contributes to study pathologic changes in SCI. Here rats were divided into a
      control group and three injury groups. Those in the injury groups were
      administered a mild, moderate, and severe contusion injury at the T10 vertebral
      level, respectively. Three rats were randomly selected from each group at 6, 24
      and 72h after SCI for imaging examination. Magnetic resonance diffusion tensor
      imaging was FA and tractography. Once magnetic resonance was completed, blood was
      collected and serum levels of neuron specific enolase (NSE) and soluble protein
      100beta (S-100beta) were determined. Then animals were sacrificed and
      histopathologic examination was conducted. The spinal cord in the SCI model rats
      produced prominent tissue damages characterized by neuronal injury in the
      affected regions. An obvious decrease in FA happened 24h after SCI, and at 72h,
      FA tended to be stable. There were significant differences in the serum levels of
      NSE and S-100beta between 6h and 24h, respectively. FA significantly related with
      the serum testing results at 24h. FA may be used as a marker for different
      severities of SCI. The optimal time for examination is at 24h post-injury in rat.

PMID- 28764934
TI  - Effects of anterior thalamic nuclei deep brain stimulation on neurogenesis in
      epileptic and healthy rats.
AB  - BACKGROUND: The efficacy of anterior thalamic nuclei (ANT) deep brain stimulation
      (DBS) in mitigating epileptic seizures has been established. Though the
      neuroprotection of ANT-DBS has been illustrated, the seizure mitigating mechanism
      of ANT-DBS has not been thoroughly elucidated. In particular, the effect of ANT
      DBS on neurogenesis has not been reported previously. METHOD: Thirty-two male
      Sprague Dawley rats were randomly assigned to the following groups: sham-DBS
      healthy (HL) (n=8), DBS-HL (n=8), sham-DBS-epilepsy (EP) (n=8) and DBS-EP (n=8).
      Normal saline and kainic acid were injected, respectively, into the former and
      later two groups, and seizures were monitored. One month later, rats received
      electrode implantation. Stimulation was exerted in the DBS group but not in the
      sham-DBS group. Next, all rats were sacrificed, and the ipsilateral hippocampus
      was dissected and prepared for quantitative real time PCR (qPCR) and western blot
      analysis in order to measure neuronal nuclear (NeuN), brain-derived neurotrophic
      factor (BDNF), doublecortin (DCX) and Ki-67 expressions. RESULTS: A 44.4% seizure
      frequency reduction was obtained after ANT-DBS, and no seizures was observed in
      healthy rats. NeuN, BDNF, Ki-67 and DCX expression levels were significantly
      decreased in the epileptic rats compared to healthy rats (P<0.01 or P<0.05).
      Obvious increases in NeuN, Ki-67 and DCX expressions were observed in epileptic
      and healthy rats receiving stimulation compared to rats receiving no stimulation
      (all Ps<0.01). However, BDNF expression was not affected by ANT-DBS (all
      Ps>0.05). CONCLUSIONS: (1) ANT-DBS reduces neuronal loss during the chronic stage
      of epilepsy. (2) Neurogenesis is elevated by ANT-DBS in both epileptic and
      healthy rats, and this elevation may not be regulated via a BDNF pathway.

PMID- 28764936
TI  - TRPC3- and ETB receptor-mediated PI3K/AKT activation induces vasogenic edema
      formation following status epilepticus.
AB  - Status epilepticus (SE, a prolonged seizure activity) is a high risk factor of
      developing vasogenic edema, which leads to secondary complications following SE.
      In the present study, we investigated whether transient receptor potential
      canonical channel-3 (TRPC3) may link vascular endothelial growth factor (VEGF)
      pathway to NFkappaB/ETB receptor axis in the rat piriform cortex during vasogenic
      edema formation. Following SE, TRPC3 and ETB receptor independently activated
      phosphatidylinositol 3 kinase (PI3K)/AKT/eNOS signaling pathway. SN50 (a NFkappaB
      inhibitor) attenuated the up-regulations of eNOS, TRPC3 and ETB receptor
      expressions following SE, accompanied by reductions in PI3K/AKT phosphorylations.
      Inhibition of SE-induced VEGF over-expression by leptomycin B also abrogated PI3K
      and AKT phosphorylations, but not TRPC3 expression. Wortmannin (a PI3K inhibitor)
      and 3CAI (an AKT inhibitor) effectively inhibited up-regulation of eNOS
      expressions and vasogenic edema lesion following SE. These findings indicate that
      PI3K/AKT may be common down-stream molecules for TRPC3- and ETB receptor
      signaling pathways during vasogenic edema formation. In addition, the present
      data demonstrate for the first time that TRPC3 may integrate VEGF- and NFkappaB
      mediated vasogenic edema formation following SE. Thus, we suggest that PI3K/AKT
      signaling pathway may be one of considerable therapeutic targets for vasogenic
      edema.

PMID- 28764937
TI  - Distinctive Changes of L-Type Calcium Channels and Dopamine Receptors in the
      Dorsomedial and Dorsolateral Striatum after the Expression of Habitual Cocaine
      Seeking Behavior in Rats.
AB  - Habitual drug-seeking behavior is essential in the transition from recreational
      drug use to compulsive drug use and is regulated by the dopamine (DA) system of
      the dorsal striatum (DS). However, a comparative study of the two subtypes of DA
      receptors, D1 receptors (D1R) and D2 receptors (D2R), which have opposite
      regulatory functions, in habitual drug-seeking behavior is absent. Moreover, the
      effects of L-type calcium channels (LTCCs) and the subtypes Cav1.2 and Cav1.3,
      which are downstream of D1R and D2R, respectively, on habitual drug-seeking
      behavior have yet to be revealed. Therefore, based on the establishment of
      habitual cocaine-seeking behavior with changeable fixed interval (FI) self
      administration (SA) training in rats, we compared the distinctive changes in D1R
      vs. D2R and Cav1.2 vs. Cav1.3 in the expression of habitual cocaine-seeking
      behavior in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS). Our
      results showed that approximately forty percent of the animals exhibited habitual
      behavior after cocaine SA training. In addition, the total and membrane Cav1.2
      and D1R in the DLS demonstrated higher expression, but the total and membrane
      Cav1.3 and D2R in the DMS demonstrated lower expression in well-established
      cocaine habitual behavior animals compared with non-established habitual behavior
      animals. These results suggested that upregulation of D1R-Cav1.2 signaling may
      enhance the function of the DLS and that inactivation of D2R-Cav1.3 caused
      depressed activity in the DMS during expression of habitual cocaine-seeking
      behavior. The imbalanced function between the DMS and DLS, which causes a shift
      from the DMS to the DLS, may mediate habitual behaviors.

PMID- 28764938
TI  - Neuroimaging techniques to assess inflammation in Multiple Sclerosis.
AB  - Multiple Sclerosis (MS) is a chronic neurological disease that represents a
      leading cause of disability in young adults and is characterized by inflammation
      and degeneration of both white matter (WM) and gray matter (GM). Defining the
      presence or absence of inflammation on individual basis is a key point in
      choosing the therapy and monitoring the treatment response. Magnetic resonance
      imaging (MRI) represents the most sensitive non-invasive tool to monitor
      inflammation in the clinical practice. Indeed, in the early phase of inflammation
      MRI detects new lesions as extrusion of gadolinium contrast agents across the
      altered blood-brain-barrier (BBB). The occurrence of MRI lesions is used to
      confirm diagnosis and has been validated as surrogate marker of relapse to
      monitor response to treatments. However, focal gadolinium-enhancing lesions
      represent only an aspect of neuroinflammation. Recent studies have suggested the
      presence of a widespread inflammation of the central nervous system (CNS), which
      is mainly related to microglial cells activation occurring both at the edge of
      chronic focal lesions and throughout the normal-appearing brain tissue. New
      imaging techniques have been developed to study diffuse inflammation taking place
      outside the focal plaques. The scope of this review is to examine the various
      neuroimaging techniques and those biophysical quantities that can be non
      invasively detected to enlighten the different aspects of neuroinflammation. Some
      techniques are commonly used in the clinical practice, while others are used in
      the research field to better understand the pathophysiological mechanisms of the
      disease and the role of inflammation.

PMID- 28764939
TI  - Exercise-related cognitive effects on sensory-motor control in athletes and
      drummers compared to non-athletes and other musicians.
AB  - Both playing a musical instrument and playing sport produce brain adaptations
      that might affect sensory-motor functions. While the benefits of sport practice
      have traditionally been attributed to aerobic fitness, it is still unknown
      whether playing an instrument might induce similar brain adaptations, or if a
      specific musical instrument like drums might be associated to specific benefits
      because of its high energy expenditure. Since the aerobic costs of playing drums
      was estimated to be comparable to those of average sport activities, we
      hypothesized that these two groups might show both behavioral and neurocognitive
      similarities. To test this hypothesis, we recruited 48 young adults and divided
      them into four age-matched groups: 12 drummers, 12 athletes, 12 no-drummer
      musicians and 12 non-athletes. Participants performed a visuo-motor
      discriminative response task, namely the Go/No-go, and their cortical activity
      was recorded by means of a 64-channel electroencephalography (EEG). Behavioral
      performance showed that athletes and drummers were faster than the other groups.
      Electrophysiological results showed that the pre-stimulus motor preparation (i.e.
      the Bereitschaftspotential or BP) and attentional control (i.e., the prefrontal
      negativity or pN), and specific post-stimulus components like the P3 and the pP2
      (reflecting the stimulus categorization process) were enhanced in the athletes
      and drummers' groups. Overall, these results suggest that playing sport and drums
      led to similar benefits at behavioral and cognitive level as detectable in a
      cognitive task. Explanations of these findings, such as on the difference between
      drummers and other musicians, are provided in terms of long-term neural
      adaptation mechanisms and increased visuo-spatial abilities.

PMID- 28764940
TI  - Draft genome sequence of a multidrug-resistant KPC-2-producing Enterobacter
      aerogenes isolated from a hospitalised patient in Brazil.
AB  - OBJECTIVES: Multidrug-resistant (MDR) Enterobacter aerogenes strains are
      frequently associated with nosocomial infections and high mortality rates,
      representing a serious public health problem. The aim of this study was to
      present the draft genome sequence of a MDR KPC-2-producing E. aerogenes isolated
      from a perineal swab of a hospitalised patient in Brazil. METHODS: Genomic DNA
      was sequenced using an Illumina MiSeq platform. De novo genome assembly was
      carried out using the A5-Miseq pipeline, and whole-genome sequence analysis was
      performed using tools from the Center for Genomic Epidemiology. RESULTS: The
      strain harboured resistance genes to beta-lactams, aminoglycosides, sulphonamides
      and trimethoprim in addition to genes encoding multidrug efflux system proteins,
      a quaternary ammonium transporter and heavy metal efflux system proteins. In
      addition, the strain harboured genes encoding diverse virulence factors.
      CONCLUSION: These data might allow a better understanding of the genetic basis of
      antimicrobial resistance and virulence in E. aerogenes strains.

PMID- 28764941
TI  - Biopsy needle tracking technique in US images.
AB  - Fast development of imaging techniques in last decades has offered the intra
      operative visualization as the integral part of surgical tools. Therefore, on
      going research activities still focus on efficient and robust analysis of
      ultrasound images. The paper meets these requirements targeting in detection of
      biopsy needle, estimation of the needle trajectory and tracking the needle tip
      motion inside the examined tissue. The developed novel method uses ultrasound
      data supported by elastography images. The investigated detection algorithm
      introduces Histogram of Oriented Gradients and image entropy, whereas the
      tracking part employs Hough transform, Gabor filter and Kanade-Lucas-Tomasi
      optical flow estimation technique. The developed methodology is verified by the
      stereoscopic navigation system. The verification phase proves the accuracy of 3
      5mm and encourages the further improvement of the methods.

PMID- 28764942
TI  - Bronchial thermoplasty for severe uncontrolled asthma in Japan.

PMID- 28764943
TI  - Occupational allergy to Triticum spelta flour.

PMID- 28764944
TI  - [Incidence of hypoxic-ischaemic encephalopathy and use of therapeutic hypothermia
      in Spain].
AB  - INTRODUCTION: There are no data on the incidence of hypoxic-ischaemic
      encephalopathy (HIE) and the implementation of therapeutic hypothermia (TH) in
      Spain. METHODS: This is a cross-sectional, national study, performed using an on
      line questionnaire targeting level III neonatal care units in Spain. Participants
      were requested to provide data of all newborns >= 35 weeks of gestational age
      diagnosed with moderate-severe HIE over a two year-period (2012-2013), and of the
      implementation of TH up to June 2015. RESULTS: All (90) contacted hospitals
      participated. HIE incidence rate was 0.77/1000 live newborns (95% CI 0.72 -
      0.83). During 2012-2013, 86% of the newborns diagnosed with moderate-severe HIE
      received TH (active or passive). Active TH was increasingly used, from 78% in
      2012 to 85% in 2013 (P=.01). Of the 14% that did not receive TH, it was mainly
      due to a delay in the diagnosis or inter-hospital transfer, and to the fact that
      the treatment was not offered. More than half (57%) were born in hospitals where
      TH was not provided, and passive hypothermia was used for inter-hospital patient
      transfer, and in 39% of the cases by inappropriately trained personnel. By June
      2015, 57 out of 90 centres had implemented TH, of which 54 performed whole-body
      TH (using servo-controlled devices). The geographical distribution of centres
      with active TH, and the number of newborn that received TH, was heterogeneous.
      CONCLUSIONS: The incidence of moderate-severe HIE is homogeneous across Spanish
      territory. Significant progress is being made in the implementation of TH,
      however it is necessary to increase the availability of active TH between
      Autonomous Communities, to improve early diagnosis, and to guarantee high quality
      patient transfer to referral centres.

PMID- 28764945
TI  - Corrigendum to "Nuclear transportation of exogenous epidermal growth factor
      receptor and androgen receptor via extracellular vesicles" [Eur J Cancer 70
      (2017) 62-74].

PMID- 28764946
TI  - Balancing act: To be, or not to be ubiquitylated.
AB  - DNA double-strand breaks (DSBs) are one of the most deleterious DNA lesions.
      Appropriate repair of DSB either by homologous recombination or non-homologous
      end-joining is critical for maintaining genome stability and fitness. DSB repair
      cooperates with cellular signalling networks, namely DSB response (DDR), which
      plays pivotal roles in the choice of DSB repair pathway, orchestrating
      recruitment of DDR factors to site of damage, transcription suppression and cell
      cycle checkpoint activation. It has been revealed that these mechanisms are
      strictly regulated, in time and space, by complex and minute ubiquitylation
      mediated reactions. Furthermore, balancing the ubiquitylation status of the DDR
      and DSB repair proteins by deubiquitylation, which is carried out by
      deubiquitylating enzymes (DUBs), is also found to be important. Recent findings
      have uncovered that DUBs are involved in various aspects of both DDR and DSB
      repair by counteracting non-proteolytic ubiquitylations in addition to protecting
      substrates from proteasomal degradation by removing proteolytic ubiquitylation.
      An advanced understanding of the detailed molecular mechanisms of the "balancing
      act" between ubiquitylation and deubiquitylation will provide novel therapeutic
      targets for diseases caused by dysfunction of DDR and DSB repair.

PMID- 28764947
TI  - Environmental mutagenesis and radiation biology: The legacy of William Morgan.
AB  - A symposium entitled Environmental Mutagenesis and Radiation Biology was held on
      September 27, 2016 to honor the memory of Dr. William F. Morgan who passed away
      unexpectedly on November 13, 2015. The speakers presented the latest reviews on
      homologous recombination repair, induced genetic instability, bystander effects,
      and risk estimate development. Their presentations are presented following the
      introduction.

PMID- 28764948
TI  - Effects of the incorporation of epsilon-aminocaproic acid/chitosan particles to
      fibrin on cementoblast differentiation and cementum regeneration.
AB  - : Cementum formation on the exposed tooth-root surface is a critical process in
      periodontal regeneration. Although various therapeutic approaches have been
      developed, regeneration of integrated and functional periodontal complexes is
      still wanting. Here, we found that the OCCM30 cementoblasts cultured on fibrin
      matrix express substantial levels of matrix proteinases, leading to the
      degradation of fibrin and the apoptosis of OCCM30 cells, which was reversed upon
      treatment with a proteinase inhibitor, epsilon-aminocaproic acid (ACA). Based on
      these findings, ACA-releasing chitosan particles (ACP) were fabricated and ACP
      incorporated fibrin (fibrin-ACP) promoted the differentiation of cementoblasts in
      vitro, as confirmed by bio-mineralization and expressions of molecules associated
      with mineralization. In a periodontal defect model of beagle dogs, fibrin-ACP
      resulted in substantial cementum formation on the exposed root dentin in vivo,
      compared to fibrin-only and enamel matrix derivative (EMD) which is used
      clinically for periodontal regeneration. Remarkably, the fibrin-ACP developed
      structural integrations of the cementum-periodontal ligament-bone complex by the
      Sharpey's fiber insertion. In addition, fibrin-ACP promoted alveolar bone
      regeneration through increased bone volume of tooth roof-of-furcation defects and
      root coverage. Therefore, fibrin-ACP can promote cementogenesis and osteogenesis
      by controlling biodegradability of fibrin, implicating the feasibility of its
      therapeutic use to improve periodontal regeneration. STATEMENT OF SIGNIFICANCE:
      Cementum, the mineralized layer on root dentin surfaces, functions to anchor
      fibrous connective tissues on tooth-root surfaces with the collagenous Sharpey's
      fibers integration, of which are essential for periodontal functioning
      restoration in the complex. Through the cementum-responsible fiber insertions on
      tooth-root surfaces, PDLs transmit various mechanical responses to periodontal
      complexes against masticatory/occlusal stimulations to support teeth. In this
      study, periodontal tissue regeneration was enhanced by use of modified fibrin
      biomaterial which significantly promoted cementogenesis within the periodontal
      complex with structural integration by collagenous Sharpey's fiber insertions in
      vivo by controlling fibrin degradation and consequent cementoblast apoptosis.
      Furthermore, the modified fibrin could improve repair and regeneration of tooth
      roof-of-furcation defects, which has spatial curvatures and geometrical
      difficulties and hardly regenerates periodontal tissues.

PMID- 28764949
TI  - Neurological outcomes of patients with history of obstructive sleep apnea after a
      cardiac arrest.
AB  - BACKGROUND: Cardiac arrest survivors may have disabilities due to hypoxic brain
      injury. Patients with obstructive sleep apnea are exposed to intermittent
      hypoxemia that may lead to ischemic preconditioning. We have hypothesized that
      patients with obstructive sleep apnea have better neurological outcomes following
      a cardiac arrest due to preconditioning of the brain. METHODS: We retrospectively
      analyzed all the survivors of in-hospital cardiac arrest from January 2006 to
      September 2016. Patients with confirmed or suspected obstructive sleep apnea were
      selected for further analysis and those without were used as comparison. Primary
      outcome was neurological functionality on hospital discharge by the Cerebral
      Performance Category. RESULTS: A total of 739 patients had cardiac arrest within
      the study period. The immediate mortality rate was 59% (N=43) in patients with
      obstructive sleep apnea and 94% (N=623) in those without (p<0.001). Approximately
      10% (N=73) were discharged alive and these were selected for further analysis.
      Patients without obstructive sleep apnea had more frequently "Poor" outcomes
      compared to those with obstructive sleep apnea (OR 2.91; 95% CI, 1.11-7.66;
      p=0.03). After adjusting in a multivariate analysis, obstructive sleep apnea was
      "protective" of "Poor" neurological outcomes: adjusted OR 0.21; 95% CI, 0.06
      0.64; p=0.01. CONCLUSION: Patients with obstructive sleep apnea had better
      unadjusted survival rates, and favorable adjusted neurological outcomes at
      discharge compared to those without obstructive sleep apnea. These results
      suggest that obstructive sleep apnea patients may tolerate better acute brain
      ischemia due to preconditioning.

PMID- 28764950
TI  - Prognosis after cardiac arrest: Vindication of the humble CT scan.

PMID- 28764951
TI  - Reconstruction of the bony chin using sagittal split osteotomies of the remaining
      mandible - A new technique for a special indication: Case report.
AB  - There are several indications for resecting the bony chin, such as squamous cell
      carcinoma, sarcoma, or benign tumors of the jaw such as ameloblastoma. Several
      techniques for reconstruction of the bony chin, such as the use of metal plates
      and also revascularized free bone grafts of the iliac crest, fibula, or scapula,
      are common. In the case of poor vascular supply, however, alternative techniques
      may be necessary. In this report, a new technique is described using pedicled
      bone flaps from both sagittally split mandibular stumps following chin resection.
      These flaps were pedicled on the mylohyoid muscles and advanced to restore the
      continuity of the mandible. An advantage of this procedure was minimization of
      the soft tissue defect, making repair easier. Morbidity of the resection and
      reconstruction was thus reduced, and recovery of the patient was very quick.

PMID- 28764952
TI  - Prospective comparison of 18F-NaF PET/CT versus 18F-FDG PET/CT imaging in
      mandibular extension of head and neck squamous cell carcinoma with dedicated
      analysis software and validation with surgical specimen. A preliminary study.
AB  - BACKGROUND: The aim of this study is to propose a new method to quantify
      radioactivity with PET/CT imaging in mandibular extension in head and neck
      squamous cell carcinoma (HNSCC), using innovative software, and to compare
      results with microscopic surgical specimens. PATIENTS AND METHODS: This
      prospective study enrolled 15 patients who underwent 18F-NaF and 18F-FDG PET/CT.
      We compared the delineations of bone invasions obtained with 18F-NaF PET/CT and
      18F-FDG PET/CT with the results of histopathological analysis of mandibular
      resections (from right and left bone borders). A method for visualization and
      quantification of PET images was developed. RESULTS: For all patients, a
      significant difference (p = 0.032 for right limits and p = 0.011 for left limits)
      was observed between 18F-FDG PET/CT imaging and histopathology results, and no
      significant difference (p = 0.88 for right limits and p = 0.55 for left limits)
      was observed between 18F-NaF PET/CT imaging and histopathology results. The right
      limits were less than 10 mm in 93% of patients, and the left limits were less
      than 10 mm in 86% of patients. CONCLUSIONS: The dedicated software enabled the
      objective delineation of radioactivity within the bone. We can confirm that 18F
      NaF is a precise and specific bone marker for the assessment of intraosseous
      mandibular extensions of head and neck cancers. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, III.

PMID- 28764953
TI  - Effect of erythritol formulation on the mortality, fecundity and physiological
      excretion in Drosophila suzukii.
AB  - Previously, we studied various combinations of non-nutritive sugars including
      erythritol and erythrose having a potentially insecticidal effect on Drosophila
      suzukii. The study suggested two potential physiological changes causing fly
      mortality: 1) starvation from the feeding of non-metabolizable erythritol and
      erythrose; 2) abnormal osmotic pressure increased in the hemolymph with
      erythritol transported from the midgut. In the present study, sucrose and
      erythritol were applied to blueberries and effects of these combinations on fly
      mortality and fecundity were monitored in the lab and greenhouse. In the lab, two
      sucrose/erythritol formulations (0.5M sucrose/2M erythritol, 1M sucrose/2M
      erythritol) resulted in the highest mortality and the lowest fecundity among D.
      suzukii adults. Two formulations, therefore, were selected for further evaluation
      with blueberry bushes and fruits in the greenhouse; fly survival with 0.5M
      sucrose/2M erythritol was significantly lower than 1M sucrose/2M erythritol for
      7days. Unlike the smaller container, mortality occurred faster in the greenhouse
      probably because flies moved more in the bigger cage accelerating the exhaustion
      of energy reserves in the body. We examined presence of erythritol in the
      hemolymph and frass to determine the nutritional metabolism and absorption of
      erythritol in D. suzukii. Unlike sucrose, a large amount of erythritol was
      observed in the hemolymph of the fly that ingested 0.5M sucrose/0.5M erythritol.
      Erythritol was also found in the frass of the same fly. The results imply that
      erythritol might be directly transported from the midgut without being
      metabolized and stored, but is accumulated in the hemolymph which in turn
      elevates the osmotic pressure in the fly hemolymph. For practical application,
      the sucrose/erythritol combination would be more effective than erythritol alone
      because the combination tastes sweeter to elicit more feeding. This erythritol
      formulation can be a potential insecticide used alone or as a delivery agent
      combined with conventional or biological insecticides to enhance their efficacy.

PMID- 28764954
TI  - Computer-Aided Detection Can Bridge the Skill Gap in Multiple Sclerosis
      Monitoring.

PMID- 28764955
TI  - The 2017 ACR Commission on Human Resources Workforce Survey.
AB  - PURPOSE: The ACR Commission on Human Resources conducts an annual workforce
      survey to determine the makeup of the radiology workforce and to identify
      potential plans for hiring new staff in an attempt to understand our profession
      better. METHODS: The Practice of Radiology Environment Database group leaders
      were asked to complete an electronic survey regarding the makeup of their present
      workforce by subspecialty, as well as the numbers and types of subspecialists
      hired in 2016 and the numbers and types of subspecialists expected to be hired in
      2017 and 2020. They were also asked about midlevel practitioners. RESULTS: Twenty
      six percent of practice leaders (477) representing 11,056 radiologists, 33% of
      all practicing radiologists in the United States, responded to the survey. The
      workforce distribution by practice type and radiologists' ages has been
      relatively stable since 2012. Six percent of the practicing workforce is over the
      age of 65 years. Sixteen percent of radiologists work part-time, and 21.5% of
      radiologists are female. The survey results indicate that 1,569 to 2,037
      radiologists were hired in 2016. In 2017, 1,826 to 2,370 new job opportunities
      are anticipated, a 14.1% increase compared with 2016. For 2017, the
      subspecialists most recruited will be neuroradiologists, general
      interventionalists, after-hours radiologists, and body imagers. Approximately
      2,156 midlevel practitioners are presently working and supervised by
      radiologists. CONCLUSIONS: The 2017 ACR workforce study shows an optimistic
      picture and outlook for those seeking jobs as practicing radiologists in 2017.
      For practice leaders, the market will be much more competitive than it has been
      in past years.

PMID- 28764957
TI  - An anisotropic multiphysics damage model with application to annulus fibrosus.
AB  - An anisotropic multiphysics damage model is developed to characterize the
      couplings among multiple physical fields within soft tissues and the tissue
      damage based on thermodynamic principles. This anisotropic multiphysics damage
      model integrates the continuum mixture theory and a continuum damage model, and
      the anisotropic damage is considered by evolution of internal damage variables
      governing the anisotropic mechanical behaviors of tissues. The energy dissipation
      associated with the transport of fluid and ions is generally related to tissue
      damage. The anisotropic multiphysics damage model is applied to simulate a case
      of annulus fibrosus (AF) damage in an isolated intervertebral disc under
      compression, to understand the damage initiation and propagation. It is found
      that, for this case (with 1000N/s of compression rate and neglected ground matrix
      damage), the damage initiated in the outer and middle posterior regions of AF at
      about 700N of axial compression. The region-dependent yield stretch ratio
      predicted by this model is consistent with experimental findings. A sensitive
      study on the damage parameters is also presented. This study provides an
      additional insight into AF damage in the isolated disc under mechanical
      compression.

PMID- 28764958
TI  - Rationale for investigating metformin as a protectant against statin-associated
      muscle symptoms.
AB  - The mechanisms underlying statin-associated muscle symptoms (SAMS) are not
      understood. Mitochondrial dysfunction and atrogin-1 activation are among the
      leading possible explanations for SAMS. Interestingly, metformin can enhance
      mitochondrial function and may affect atrogin-1 expression. Therefore, we sought
      to perform a systematic search of the literature to explore the relationship
      among statins, metformin, and SAMS.

PMID- 28764959
TI  - Photoprotective responses in a brown macroalgae Cystoseira tamariscifolia to
      increases in CO2 and temperature.
AB  - Global warming and ocean acidification are increasingly affecting coastal
      ecosystems, with impacts that vary regionally depending upon local biogeography.
      Ocean acidification drives shifts in seaweed community dominance that depend on
      interactions with other factors such as light and nutrients. In this study, we
      investigated the photophysiological responses in the brown macroalgae species
      Cystoseira tamariscifolia (Hudson) Papenfuss with important structural role in
      the coastal Mediterranean communities. These algae were collected in the Cabo de
      Gata-Nijar Natural Park in ultraoligotrophic waters (algae exposed under high
      irradiance and less nutrient conditions) vs. those collected in the La Arana
      beach in oligotrophic waters (algae exposed at middle nutrient and irradiance
      conditions) in the Mediterranean Sea. They were incubated in mesocosms, under two
      levels of CO2; ambient (400-500 ppm) and high CO2 (1200-1300 ppm), combined with
      two temperatures (ambient temperature; 20  degrees C and ambient temperature + 4 
      degrees C; 24  degrees C) and the same nutrient conditions of the waters of the
      origin of macroalgae. Thalli from two sites on the Spanish Mediterranean coast
      were significantly affected by increases in pCO2 and temperature. The carotenoids
      (fucoxanthin, violaxanthin and beta-carotene) contents were higher in algae from
      oligotrophic than that from ultraoligotrophic water, i.e., algae collected under
      higher nutrient conditions respect to less conditions, increase photoprotective
      pigments content. Thalli from both locations upregulated photosynthesis (as
      Fv/Fm) at increased pCO2 levels. Our study shows that ongoing ocean acidification
      and warming can increase photoprotection and photosynthesis in intertidal
      macroalgae.

PMID- 28764960
TI  - Contrasting effects of a classic Nrf2 activator, tert-butylhydroquinone, on the
      glutathione-related antioxidant defenses in Pacific oysters, Crassostrea gigas.
AB  - Nrf2 is a well-known transcription factor controlling a number of antioxidant
      defense-related genes, which is understudied in bivalves. In this study, oysters
      Crassostrea gigas were exposed for 24, 48 and 96 h to 10 or 30 MUM tert
      butylhydroquinone (tBHQ), a classic Nrf2 activator. At 96 h, a clear induction of
      GSH-related antioxidant defenses was observed in gills of tBHQ-exposed animals,
      including GSH, glutathione S-transferase (GST), glutathione peroxidase (GPx) and
      glutathione reductase (GR). Unexpectedly, the activities of GST, GPx and GR were
      significantly decreased 24 h after tBHQ treatment, suggesting a possible
      inhibition, which was supported by in vitro experiments. GR mRNA (24 h) and
      protein levels (24 and 96 h) were increased by tBHQ treatment, confirming its
      induction, possibly by the Nrf2 pathway. The conserved domains at C. gigas Keap1
      and Nrf2 proteins and the clear induction of GSH-related antioxidant defenses by
      tBHQ, a classical Nrf2 inducer, support the idea of a functional Nrf2/Keap1
      pathway in bivalves. tBHQ also proved to be a tool to explore redox regulatory
      mechanisms in bivalves.

PMID- 28764961
TI  - Structure of macroalgal communities on tropical rocky shores inside and outside a
      marine protected area.
AB  - The structure of marine macroalgal communities and morpho-functional groups were
      investigated in a poorly characterized region on the Tropical Southwestern
      Atlantic coast, Brazil. The survey was conducted at six rocky shores located on
      the mainland and on coastal islands distributed inside a marine protected area
      (MPA) and outside the MPA (near a densely populated area). We hypothesized that
      tropical rocky shores inside the MPA and islands have higher species richness,
      diversity, and evenness of marine macroalgae. Results confirmed that species
      richness, diversity and evenness were significantly higher inside the MPA than in
      rocky shores outside the MPA. Only species richness was higher on islands than on
      the mainland. The results suggest that human impacts could lead to a competitive
      advantage and dominance in the articulated calcareous morphotype, resulting in
      community differences and lower benthic biodiversity in tropical ecosystems near
      urbanized sites.

PMID- 28764956
TI  - Microbiome and metabolome data integration provides insight into health and
      disease.
AB  - For much of our history, the most basic information about the microbial world has
      evaded characterization. Next-generation sequencing has led to a rapid increase
      in understanding of the structure and function of host-associated microbial
      communities in diverse diseases ranging from obesity to autism. Through
      experimental systems such as gnotobiotic mice only colonized with known microbes,
      a causal relationship between microbial communities and disease phenotypes has
      been supported. Now, microbiome research must move beyond correlations and
      general demonstration of causality to develop mechanistic understandings of
      microbial influence, including through their metabolic activities. Similar to the
      microbiome field, advances in technologies for cataloguing small molecules have
      broadened our understanding of the metabolites that populate our bodies.
      Integration of microbial and metabolomics data paired with experimental
      validation has promise for identifying microbial influence on host physiology
      through production, modification, or degradation of bioactive metabolites.
      Realization of microbial metabolic activities that affect health is hampered by
      gaps in our understanding of (1) biological properties of microbes and
      metabolites, (2) which microbial enzymes/pathways produce which metabolites, and
      (3) the effects of metabolites on hosts. Capitalizing on known mechanistic
      relationships and filling gaps in our understanding has the potential to enable
      translational microbiome research across disease contexts.

PMID- 28764962
TI  - Chiral-pool synthesis of 1,2,4-trisubstituted 1,4-diazepanes as novel sigma1
      receptor ligands.
AB  - Starting from enantiomerically pure amino acids, 1,4-diazepanes with various
      substituents in 1, 2, and 4-position were synthesized following the late stage
      diversification strategy. The key step in the formation of the seven-membered
      ring was the intramolecular EDC coupling of amino acids 15, 26, and 39. The
      configuration in 2-position does not influence the sigma1 affinity and
      selectivity over related receptors. A cyclohexylmethyl or a butyl group are the
      preferred substituents in 4-position, whereas a methyl moiety in 2-position and a
      (substituted) benzyl moiety in 1-position result in the highest sigma1 affinity.
      These results fit nicely to the reported sigma1 pharmacophore models. The
      compounds did not inhibit the structurally related fungal enzyme sterol Delta8,7
      isomerase, but showed inhibition of diverse enzymes in late cholesterol
      biosynthesis at high concentrations. In a screening against more than 50 target
      proteins, (2S)-1-benzyl-4-(4-methoxybenzyl)-2-methyl-1,4-diazepane ((S)-28b,
      Ki(sigma1)=0.86nM) showed a clean receptor profile. The dose dependent
      potentiation of electrically stimulated contractions of guinea pig vas deferens
      indicates sigma1 agonistic activity of (S)-28b. Even at a dose of 100mg/kg (S)
      28b did not induce severe toxic or behavioral effects in the Irwin screen. Clear
      cognition enhancing effects were observed for (S)-28b after inducing amnesia by
      scopolamine.

PMID- 28764963
TI  - Mapping the substrate scope of monoamine oxidase (MAO-N) as a synthetic tool for
      the enantioselective synthesis of chiral amines.
AB  - A library of 132 racemic chiral amines (alpha-substituted methylbenzylamines,
      benzhydrylamines, 1,2,3,4-tetrahydronaphthylamines (THNs), indanylamines, allylic
      and homoallylic amines, propargyl amines) was screened against the most versatile
      monoamine oxidase (MAO-N) variants D5, D9 and D11. MAO-N D9 exhibited the highest
      activity for most substrates and was applied to the deracemisation of a
      comprehensive set of selected primary amines. In all cases, excellent
      enantioselectivity was achieved (e.e. >99%) with moderate to good yields (55
      80%). Conditions for the deracemisation of primary amines using a MAO-N/borane
      system were further optimised using THN as a template addressing substrate load,
      nature of the enzyme preparation, buffer systems, borane sources, and organic co
      solvents.

PMID- 28764964
TI  - Motor deficits, impaired response inhibition, and blunted response to
      methylphenidate following neonatal exposure to decabromodiphenyl ether.
AB  - Decabromodiphenyl ether (decaBDE) is an applied brominated flame retardant that
      is widely-used in electronic equipment. After decades of use, decaBDE and other
      members of its polybrominated diphenyl ether class have become globally
      distributed environmental contaminants that can be measured in the atmosphere,
      water bodies, wildlife, food staples and human breastmilk. Although it has been
      banned in Europe and voluntarily withdrawn from the U.S. market, it is still used
      in Asian countries. Evidence from epidemiological and animal studies indicate
      that decaBDE exposure targets brain development and produces behavioral
      impairments. The current study examined an array of motor and learning behaviors
      in a C57BL6/J mouse model to determine the breadth of the developmental
      neurotoxicity produced by decaBDE. Mouse pups were given a single daily oral dose
      of 0 or 20mg/kg decaBDE from postnatal day 1 to 21 and were tested in adulthood.
      Exposed male mice had impaired forelimb grip strength, altered motor output in a
      circadian wheel-running procedure, increased response errors during an operant
      differential reinforcement of low rates (DRL) procedure and a blunted response to
      an acute methylphenidate challenge administered before DRL testing. With the
      exception of altered wheel-running output, exposed females were not affected.
      Neither sex had altered somatic growth, motor coordination impairments on the
      Rotarod, gross learning deficits during operant lever-press acquisition, or
      impaired food motivation. The overall pattern of effects suggests that males are
      more sensitive to developmental decaBDE exposure, especially when performing
      behaviors that require effortful motor output or when learning tasks that require
      sufficient response inhibition for their successful completion.

PMID- 28764965
TI  - Atorvastatin repurposing for the treatment of cryptosporidiosis in experimentally
      immunosuppressed mice.
AB  - The present study was conducted on 200 male mice for the detection of the effect
      of Atorvastatin on Cryptosporidium spp. infection versus the commercially used
      drug Nitazoxanide in experimentally immunosuppressed mice. Atorvastatin was used
      alone at low dose (20 mg/kg), high dose (40 mg/kg), and combined with
      Nitazoxanide (1000 mg/kg) with either the low dose or high dose for five
      consecutive days. Parasitological assessment of the drug effect was done using
      Modified Z-N staining of stool samples collected from mice. Results revealed a
      reduction of the number of oocysts shed with percentage of reduction on the 21st
      day post infection by 53.7%, 67.2%, 70.1% &77.5%, respectively, compared to the
      infected untreated group. The Nitazoxanide treated group showed 52.7% reduction.
      In addition, examination of small and large intestinal contents after mice
      scarification revealed reduced numbers of oocysts by 56.2%-58.8%, 65.1%-65.3%,
      70.6%-73.9% and 77.8%-79.9%, respectively, compared to 51.2%-54.1% in
      Nitazoxanide treated group. The histopathological examination of sections from
      duodenum, jejunum, ileum, colon, stomach and lungs also revealed a significant
      improvement of the histopathological changes in Atorvastatin treated groups and
      more remarkable improvement in the groups treated with combined drugs as compared
      to infected untreated group. Accordingly, the combination of Atorvastatin and
      Nitazoxanide showed a synergistic effect through reduction of the number of
      oocysts shed and improvement of the histopathological changes induced by
      Cryptosporidium spp. infection in the small intestine, colon, stomach and lungs
      of infected immunosuppressed mice in comparison to that induced by either
      Nitazoxanide or Atorvastatin alone.

PMID- 28764967
TI  - Ultrasound Imaging of Muscle Contraction of the Tibialis Anterior in Patients
      with Facioscapulohumeral Dystrophy.
AB  - A need exists for biomarkers to diagnose, quantify and longitudinally follow
      facioscapulohumeral muscular dystrophy (FSHD) and many other neuromuscular
      disorders. Furthermore, the pathophysiological mechanisms leading to muscle
      weakness in most neuromuscular disorders are not completely understood. Dynamic
      ultrasound imaging (B-mode image sequences) in combination with speckle tracking
      is an easy, applicable and patient-friendly imaging tool to visualize and
      quantify muscle deformation. This dynamic information provides insight in the
      pathophysiological mechanisms and may help to distinguish the various stages of
      diseased muscle in FSHD. In this proof-of-principle study, we applied a speckle
      tracking technique to 2-D ultrasound image sequences to quantify the deformation
      of the tibialis anterior muscle in patients with FSHD and in healthy controls.
      The resulting deformation patterns were compared with muscle ultrasound echo
      intensity analysis (a measure of fat infiltration and dystrophy) and clinical
      outcome measures. Of the four FSHD patients, two patients had severe peroneal
      weakness and two patients had mild peroneal weakness on clinical examination. We
      found a markedly varied muscle deformation pattern between these groups: patients
      with severe peroneal weakness showed a different motion pattern of the tibialis
      anterior, with overall less displacement of the central tendon region, while
      healthy patients showed a non-uniform displacement pattern, with the central
      aponeurosis showing the largest displacement. Hence, dynamic muscle ultrasound of
      the tibialis anterior muscle in patients with FSHD revealed a distinctively
      different tissue deformation pattern among persons with and without tibialis
      anterior weakness. These findings could clarify the understanding of the
      pathophysiology of muscle weakness in FSHD patients. In addition, the change in
      muscle deformation shows good correlation with clinical measures and quantitative
      muscle ultrasound measurements. In conclusion, dynamic ultrasound in combination
      with speckle tracking allows the study of the effects of muscle pathology in
      relation to strength, force transmission and movement generation. Although
      further research is required, this technique can develop into a biomarker to
      quantify muscle disease severity.

PMID- 28764966
TI  - Cathelicidins display conserved direct antiviral activity towards rhinovirus.
AB  - Human rhinoviruses (HRVs) are the most common cause of viral respiratory tract
      infections, and are associated with significant morbidity and mortality in
      immunocompromised individuals and patients with pre-existing pulmonary
      conditions. The therapeutic options available are extremely limited and therefore
      novel therapeutics for HRV infections are of significant interest. Cathelicidins
      have been shown to have potent antiviral activity against a range of pathogens
      and are known to be key immunomodulatory mediators during infection. We therefore
      assessed the antiviral potential of cathelicidins from humans and other mammalian
      species against HRV, together with the potential for the human cathelicidin to
      modulate apoptotic pathways and alter cell viability during HRV infection. We
      demonstrate that LL-37, the porcine cathelicidin Protegrin-1, and the ovine
      cathelicidin SMAP-29 display potent antiviral activity towards HRV and that this
      activity is visible when either the virus is exposed to the peptides prior to
      cell infection or after cells have been infected. We further demonstrate that, in
      contrast to established findings with bacterial infection models, LL-37 does not
      induce apoptosis or necrosis in HRV-infected lung epithelial cells at
      physiological or superphysiological concentrations, but does reduce the metabolic
      activity of infected cells compared to uninfected cells treated with similar
      peptide concentrations. Collectively, the findings from this study demonstrate
      that the mechanism of action of cathelicidins against rhinovirus is by directly
      affecting the virus and we propose that the delivery of exogenous cathelicidins,
      or novel synthetic analogues, represent an exciting and novel therapeutic
      strategy for rhinovirus infection.

PMID- 28764968
TI  - Production of human milk oligosaccharides by enzymatic and whole-cell microbial
      biotransformations.
AB  - Human milk oligosaccharides (HMO) are almost unique constituents of breast milk
      and are not found in appreciable amounts in cow milk. Due to several positive
      aspects of HMO for the development, health, and wellbeing of infants, production
      of HMO would be desirable. As a result, scientists from different disciplines
      have developed methods for the preparation of single HMO compounds. Here, we
      review approaches to HMO preparation by (chemo-)enzymatic syntheses or by whole
      cell biotransformation with recombinant bacterial cells. With lactose as acceptor
      (in vitro or in vivo), fucosyltransferases can be used for the production of 2'
      fucosyllactose, 3-fucosyllactose, or more complex fucosylated core structures.
      Sialylated HMO can be produced by sialyltransferases and trans-sialidases. Core
      structures as lacto-N-tetraose can be obtained by glycosyltransferases from
      chemical donor compounds or by multi-enzyme cascades; recent publications also
      show production of lacto-N-tetraose by recombinant Escherichia coli bacteria and
      approaches to obtain fucosylated core structures. In view of an industrial
      production of HMOs, the whole cell biotransformation is at this stage the most
      promising option to provide human milk oligosaccharides as food additive.

PMID- 28764969
TI  - Peptide nucleic acids: Advanced tools for biomedical applications.
AB  - Peptide Nucleic Acids (PNAs) are the DNA/RNA analogues in which sugar-phosphate
      backbone is replaced by N-2-aminoethylglycine repeating units. PNA contains
      neutral backbone hence due to the absence of electrostatic repulsion, its
      hybridization shows remarkable stability towards complementary oligonucleotides.
      PNAs are highly resistant to cleavage by chemicals and enzymes due to the
      substrate specific nature of enzymes and therefore not degraded inside the cells.
      PNAs are emerging as new tools in the market due to their applications in
      antisense and antigene therapies by inhibiting translation and transcription
      respectively. Hence, several methods based on PNAs have been developed for
      designing various anticancer and antigene drugs, detection of mutations or
      modulation of PCR reactions. The duplex homopurine sequence of DNA may also be
      recognized by PNA, forming firm PNA/DNA/PNA triplex through strand invasion with
      a looped-out DNA strand. PNAs have also been found to replace DNA probes in
      varied investigative purposes. There are several disadvantages regarding cellular
      uptake of PNA, so modifications in PNA backbone or covalent coupling with cell
      penetrating peptides is necessary to improve its delivery inside the cells. In
      this review, hybridization properties along with potential applications of PNA in
      the field of diagnostics and pharmaceuticals are elaborated.

PMID- 28764970
TI  - Urinary-exosomal miR-2909: A novel pathognomonic trait of prostate cancer
      severity.
AB  - The global occurrence of prostate cancer with a range of patient outcome has
      prompted various investigators to explore novel molecular biomarkers that can
      precisely detect and track this type of cancer severity. Several studies suggest
      that micro-RNAs have emerged to act as a new largely unexplored class of
      biomarkers because of their inherent stability, resilience and recruitment into
      exosomes present in various human body fluids. With this study, we aim to reveal
      the nature of urinary-exosomal miR-2909 & miR-615-3p recruitment in patients
      suffering from either prostate cancer (n=90) or bladder cancer (n=60) as compared
      to that in either prostate disease-control subjects having benign prostate
      hyperplasia (n=10) or healthy subjects (n=50). Unlike miR-615-3p, the urinary-
      exosomal miR-2909 recruitment was not only observed conspicuously in subjects
      having prostate cancer in comparison to bladder cancer but also the extent of
      urinary exosomal miR-2909 recruitment showed characteristic variation as a
      function of prostate cancer aggressiveness as compared to that of either urinary-
      exosomal miR-615-3p level or existing widely recognised serum prostate specifics
      antigen (PSA) biomarker of this cancer. In summary, we propose that the extent of
      urinary exosomal miR-2909 recruitment may provide a potential non-invasive
      candidate diagnostic marker for the detection of prostate cancer and its
      aggressiveness.

PMID- 28764971
TI  - Development and validation of two phantoms for quality control in cone-beam CT.
AB  - This study aimed at the development and validation of the models of phantom: CQ
      02-IFBA and CQ-01-IFBA, the first filled with water and the second fully with a
      solid structure in polymethylmethacrylate (PMMA). Both models allow its use in
      various models of cone beam computed tomography (CBCT), independent of the size
      of the field of view. The two phantoms are used to evaluate seven parameters of
      quality control: intensity or average value of pixels of five different plastics,
      signal to noise ratio, resolution, low contrast, spatial resolution, the accuracy
      of distances on the z axis, the geometric distortion and image uniformity.
      Spatial resolution is a critical parameter that differs significantly in the
      various imaging modalities in dental radiology, and in these two phantoms, it can
      be evaluated by two different methods: MTF obtained by Fourier transformation of
      the function LSF (line spread function) and/or by analysis visual image to a
      pattern of bars up to 16 lp/cm. Validation was performed in three models CBCT:
      CareStream CS 9000 3D, i-CAT Classical and Sirona Orthophos XG 3D. The two
      phantom models were viable and also complied with the specifications and data
      available in the literature. It is concluded that the two phantom models are
      viable for use in CBCT with different characteristics.

PMID- 28764972
TI  - Diagnostic Accuracy of Clinical Decision Rules to Exclude Fractures in Acute
      Ankle Injuries: Systematic Review and Meta-analysis.
AB  - BACKGROUND: Ankle decision rules are developed to expedite patient care and
      reduce the number of radiographs of the ankle and foot. Currently, only three
      systematic reviews have been conducted on the accuracy of the Ottawa Ankle and
      Foot Rules (OAFR) in adults and children. However, no systematic review has been
      performed to determine the most accurate ankle decision rule. OBJECTIVES: The
      purpose of this study is to examine which clinical decision rules are the most
      accurate for excluding ankle fracture after acute ankle trauma. METHODS: A
      systematic search was conducted in the databases PubMed, CINAHL, PEDro,
      ScienceDirect, and EMBASE. The sensitivity, specificity, likelihood ratios, and
      diagnostic odds ratio of the included studies were calculated. A meta-analysis
      was conducted if the accuracy of a decision rule was available from at least
      three different experimental studies. RESULTS: Eighteen studies satisfied the
      inclusion criteria. These included six ankle decision rules, specifically, the
      Ottawa Ankle Rules, Tuning Fork Test, Low Risk Ankle Rule, Malleolar and Midfoot
      Zone Algorithms, and the Bernese Ankle Rules. Meta-analysis of the Ottawa Ankle
      Rules (OAR), OAFR, Bernese Ankle Rules, and the Malleolar Zone Algorithm resulted
      in a negative likelihood ratio of 0.12, 0.14, 0.39, and 0.23, respectively.
      CONCLUSION: The OAR and OAFR are the most accurate decision rules for excluding
      fractures in the event of an acute ankle injury.

PMID- 28764973
TI  - Disturbed Desmoglein-2 in the intercalated disc of pediatric patients with
      dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) leads to disturbed contraction and force
      transduction, and is associated with substantial mortality in all age groups.
      Involvement of a disrupted composition of the intercalated disc (ID) has been
      reported. However, in children, little is established about such subcellular
      changes during disease, because of the pathological mix-up with the ongoing
      cardiac maturation. This leaves maladaptive remodeling often undetected. We aimed
      at illustrating subcellular alterations in children diagnosed with DCM compared
      to age-matched controls, focusing on ID proteins known to be crucially stable
      under healthy conditions and destabilized during cardiac injury in adults. Left
      ventricular or septal pediatric specimens were collected from 7 individuals
      diagnosed with DCM (age: 23 weeks in utero to 8 weeks postnatal) and age-matched
      controls that died of non-cardiovascular cause. We determined the amount of
      fibrosis and localization of ID proteins by immunohistochemistry. In pediatric
      DCM, most ID proteins follow similar spatiotemporal changes in localization as in
      controls. However, although no mutations were found, the signal of the desmosomal
      protein Desmoglein-2 was reduced in all pediatric DCM specimens, but not in
      controls or adult DCM patients. Endocardial and transmural fibrosis was increased
      in all pediatric DCM patients compared to age-matched controls. Composition of
      the ID in pediatric DCM patients is similar to controls, except for the
      localization of Desmoglein-2 and presence of severe fibrosis. This suggests that
      the architecture of desmosomes is already disturbed in the early stages of DCM.
      These findings contribute to the understanding of pediatric DCM.

PMID- 28764975
TI  - A new prospect in magnetic nanoparticle-based cancer therapy: Taking credit from
      mathematical tissue-mimicking phantom brain models.
AB  - Distribution patterns/performance of magnetic nanoparticles (MNPs) was visualized
      by computer simulation and experimental validation on agarose gel tissue
      mimicking phantom (AGTMP) models. The geometry of a complex three-dimensional
      mathematical phantom model of a cancer tumor was examined by tomography imaging.
      The capability of mathematical model to predict distribution patterns/performance
      in AGTMP model was captured. The temperature profile vs. hyperthermia duration
      was obtained by solving bio-heat equations for four different MNPs distribution
      patterns and correlated with cell death rate. The outcomes indicated that bio
      heat model was able to predict temperature profile throughout the tissue model
      with a reasonable precision, to be applied for complex tissue geometries. The
      simulation results on the cancer tumor model shed light on the effectiveness of
      the studied parameters.

PMID- 28764976
TI  - More than just noise: Inter-individual differences in fear acquisition,
      extinction and return of fear in humans - Biological, experiential, temperamental
      factors, and methodological pitfalls.
AB  - Why do only some individuals develop pathological anxiety following adverse
      events? Fear acquisition, extinction and return of fear paradigms serve as
      experimental learning models for the development, treatment and relapse of
      anxiety. Individual differences in experimental performance were however mostly
      regarded as 'noise' by researchers interested in basic associative learning
      principles. Our work for the first time presents a comprehensive literature
      overview and methodological discussion on inter-individual differences in fear
      acquisition, extinction and return of fear. We tell a story from noise that
      steadily develops into a meaningful tune and converges to a model of mechanisms
      contributing to individual risk/resilience with respect to fear and anxiety
      related behavior. Furthermore, in light of the present 'replicability crisis' we
      identify methodological pitfalls and provide suggestions for study design and
      analyses tailored to individual difference research in fear conditioning.
      Ultimately, synergistic transdisciplinary and collaborative efforts hold promise
      to not only improve our mechanistic understanding but can also be expected to
      contribute to the development of specifically tailored ('individualized')
      intervention and targeted prevention programs in the future.

PMID- 28764974
TI  - Associations between genetic and epigenetic variations in cytokine genes and mild
      persistent breast pain in women following breast cancer surgery.
AB  - Persistent pain following breast cancer surgery is a significant problem. Both
      inherited and acquired mechanisms of inflammation appear to play a role in the
      development and maintenance of persistent pain. In this longitudinal study,
      growth mixture modeling was used to identify persistent breast pain phenotypes
      based on pain assessments obtained prior to and monthly for 6months following
      breast cancer surgery. Associations between the "no pain" and "mild pain"
      phenotypes and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes
      were evaluated. The methylation status of the CpG sites found in the promoters of
      genes associated with pain group membership was determined using bisulfite
      sequencing. In the multivariate analysis, three SNPs (i.e., interleukin 6 (IL6)
      rs2069840, C-X-C motif chemokine ligand 8 (CXCL8) rs4073, tumor necrosis factor
      (TNF) rs1800610) and two TNF CpG sites (i.e., c.-350C, c.-344C) were associated
      with pain group membership. These findings suggest that variations in IL6, CXCL8,
      and TNF are associated with the development and maintenance of mild persistent
      breast pain. CpG methylation within the TNF promoter may provide an additional
      mechanism through which TNF alters the risk for mild persistent breast pain after
      breast cancer surgery. These genetic and epigenetic variations may help to
      identify individuals who are predisposed to the development of mild levels of
      persistent breast pain following breast cancer surgery.

PMID- 28764977
TI  - Hypomethylation of BORIS is a promising prognostic biomarker in hepatocellular
      carcinoma.
AB  - The brother of the regulator of the imprinted site (BORIS), an 11 zinc finger
      (ZF) protein, is a paralogue of CCCTC-binding factor (CTCF), involves in a few
      crucial events of chromatin functions, complex transcription regulation during
      spermatogenesis. As a novel tumor oncogene, abnormal expression of BORIS is
      observed in human hepatocellular carcinoma, however, the underlying mechanisms
      remain largely unexplored. In this study, the methylation status of BORIS was
      tested by methylation specific polymerase chain reaction (MSP) in human HCC cell
      lines and 43 pairs of tissue specimens. Frequently demethylation of BORIS in HCC
      was significantly higher than that in the paired adjacent non-tumor tissues
      (P=0.019), and it was correlated with tumor size (P=0.025) and clinical TNM stage
      (P=0.035). Patients with hypomethylated BORIS had a shorter disease free survival
      than those without demethylated BORIS (P=0.006). Further, analyses using Cox
      regression have indicated that the BORIS demethylation status was an independent
      risk to the reduced overall survival rate of HCC patients (P=0.035). These
      findings provide clues to clarify whether the demethylation may lead to
      activation of the promoter for upregulation expression of BORIS. In conclusions,
      aberrant BORIS hypomethylation is a promising biomarker for the prognosis of HCC.

PMID- 28764978
TI  - Vitamin D and K signaling pathways in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a primary liver malignancy, and is now the six
      most common in between malignancies. Early diagnosis of HCC with prompt treatment
      increases the opportunity of patients to survive. With the advances in
      understanding the molecular biology of HCC, new therapeutic strategies to treat
      HCC have emerged. There is a growing consensus that vitamins are important for
      the control of various cancers. Biochemical evidence clearly indicates that HCC
      cells are responsive to the inhibitory effect of vitamin D, vitamin D analogues
      and vitamin K. In this review, we summarize the mechanisms used by vitamin D and
      K to influence the development of HCC and the latest development of vitamin
      analogues for potential HCC therapy.

PMID- 28764979
TI  - Apical Periodontitis, a Predictor Variable for Preeclampsia: A Case-control
      Study.
AB  - INTRODUCTION: Preeclampsia (PE) is characterized by hypertension and proteinuria
      after the 20th week of gestation. There is an association between systemic
      inflammation and adverse pregnancy outcomes such as PE. Therefore, for the first
      time, the present study aimed to investigate the possible association between
      maternal apical periodontitis (AP) and PE. METHODS: In this case-control study,
      50 mothers who were diagnosed with PE during pregnancy were included in the
      experimental group. The control group consisted of 50 matched mothers with a
      normal course of pregnancy. The endodontic and periodontal status of all
      participants was reviewed using the digital panoramic radiographs that were
      available before pregnancy. The number of remaining teeth and the presence of AP
      in all teeth and endodontically treated teeth were recorded using the periapical
      index. Binary logistic regression was used to determine the possible association
      between AP and PE (alpha = 0.05). RESULTS: AP in at least 1 tooth was found in 27
      of the mothers who developed PE (54%) and in 16 of the control patients (32%)
      (odds ratio [OR] = 2.4, P < .05). Adjusted for the maternal periodontitis, number
      of teeth, and endodontic treatment, maternal AP was significantly associated with
      the occurrence of PE (P < .05; OR = 2.23; 95% confidence interval, 95% = 1.92
      6.88). CONCLUSIONS: AP was significantly more prevalent in the experimental
      group. For the first time, this study has provided evidence that maternal AP may
      be a strong independent predictor of PE. Considering the high occurrence of PE,
      particularly in developing countries, it could be suggested that the risk of PE
      may be reduced through comprehensive dental examinations for detecting and
      treating any source of inflammation, including AP, before pregnancy.

PMID- 28764980
TI  - 20-year Follow-up of Recurrent Glandular Odontogenic Cyst Mimicking a Periapical
      Lesion.
AB  - Periapical lesions usually are caused by root canal infection; nevertheless,
      other pathologies may eventually involve the tooth apex, making the correct
      diagnosis more difficult. Glandular odontogenic cysts (GOCs) are uncommon and,
      despite their cystic nature, may present an aggressive behavior and a high
      recurrence rate. This report describes a recurrent GOC mimicking a periapical
      lesion that was followed up for 20 years. A 45-year-old woman described tooth
      discomfort for several years in the anterior region of the mandible that was not
      exacerbated during eating or occlusion. Clinical examination revealed no signs of
      swelling, redness, or inflammation in the gingival or surrounding soft tissue.
      Nevertheless, periapical radiography showed a well-defined large radiolucent
      lesion in the periapical region of teeth #22, #23, #24, and #25. The pulp test
      confirmed that all these teeth were vital. An incisional biopsy was performed,
      and with the histopathological diagnosis of an odontogenic cyst, the lesion was
      enucleated surgically. After recurrence, the extensive periapical multilocular
      lesions were again surgically removed. Based on the microscopic findings, the
      final diagnosis was GOC. One year later, there were no signs of recurrence. GOCs
      associated with the root apex may mimic periapical inflammatory diseases.
      Clinical, radiographic, and histopathological findings are essential for the
      diagnosis of inconclusive radiolucent findings in the periapical region. Biopsy
      specimens should be sent to a specialized oral pathology laboratory.

PMID- 28764981
TI  - Promises and limitations of nanoparticles in the era of cell therapy: Example
      with CD19-targeting chimeric antigen receptor (CAR)-modified T cells.
AB  - A number of nanoparticles has been developed by chemists for biomedical
      applications to meet imaging and targeting needs. In parallel, adoptive T therapy
      with chimeric antigen receptor engineered T cells (CART cells) has recently held
      great promise in B-cell malignancy treatments thanks to the development of anti
      CD19 CAR T cells. Indeed, CD19 is a reliable B cell marker and a validated target
      protein for therapy. In this perspective article, we propose to discuss the
      advantages, limits and challenges of nanoparticles and CAR T cells, focusing on
      CD19 targeting objects: anti-CD19 nanoparticles and anti-CD19 CAR T cells,
      because those genetically-modified cells are the most widely developed in
      clinical setting. In the first part, we will introduce B cell malignancies and
      the CD19 surface marker. Then we will present the positioning of nanomedicine in
      the topic of B cell malignancy, before exposing CAR T technology. Finally, we
      will discuss the complementary approaches between nanoparticles and CAR T cells.

PMID- 28764982
TI  - Improvement in insulin absorption into gastrointestinal epithelial cells by using
      molecularly imprinted polymer nanoparticles: Microscopic evaluation and
      ultrastructure.
AB  - A molecularly imprinted polymer nanoparticle (MIP) was prepared by integrating a
      mixed functional monomer into a highly cross-linked polymer. The nanosized
      insulin as a template transferred into the binding cavities, anchored functional
      monomer(s) that the insulin structure formed within free space of the molecular
      size region by MIP nanoparticles. The oral administration with the insulin-loaded
      MIP resulted in higher fluorescence intensity of rhodamine-labeled insulin into
      the epithelial cells. We observed the correlation between the lipophilic domains
      of dye over the affected areas of sites with the interplay of the intestinal
      epithelial layer on the different intestinal sections. And, the detection with
      guinea pig anti-insulin antibody followed by goat anti-guinea pig antibody
      clearly elicited the efficient insulin function in the necessary biological
      milieu. The root mean square roughness of the MIP indicated difference of the
      surface density, significantly lower compared with the polymer attributed to the
      protein-mucin uptake that efficiently promoted the insulin penetration.
      Eventually electron microscopy data of the conjugated biotin-gold nanoparticles
      showed the transport of insulin across the intestinal epithelium via
      transcellular pathway, and the development of the pancreatic beta cell in the
      streptozocin-induced diabetic rats. Histopathological observation exhibited no
      obvious toxic effect after orally treated with MIP loaded insulin (100mg/kg)
      daily for 14days compared to control group. The use of an insulin-loaded MIP was
      proven to be an effective therapeutic protein delivery through transmucosal oral
      route.

PMID- 28764983
TI  - Targeted delivery of probiotics to enhance gastrointestinal stability and
      intestinal colonisation.
AB  - The aim of this work was to assess the viability of some commercial probiotics
      after exposure to gastric acid and the possibility of modifying these
      formulations for delivery into the distal parts of the intestines.
      Gastrointestinal tolerance testing was conducted for three commercial probiotics
      and an in-house freeze-dried Lactobacillus acidophilus strain. The contents of
      the commercial products and the in-house freeze-dried strain were then loaded
      into capsules for site-specific delivery into the colon using the Phloral(r)
      coating technology; the viability upon release was then ascertained. An
      assessment of the potential of these products to adhere to intestinal cells was
      also conducted. The results showed that all the commercial products contained the
      minimum number of probiotic strains as indicated on their respective packages.
      When gastric acid tolerance tests were performed on these products, all the
      commercial probiotics and the prepared freeze-dried strain demonstrated over 106
      CFU reductions within 5min. When these were encapsulated for site-specific
      delivery into the distal parts of the gut, viabilities of approximately 90% were
      obtained after these capsules had been initially deposited in gastric acid for
      2h. An evaluation of the ability of the probiotic formulations to adhere to
      intestinal cells demonstrated adhesion in the range 64-76% for the products
      evaluated. The need to target the delivery of probiotics into the intestines has
      been demonstrated here as this offers a greater potential for colonisation of the
      intestines once the harshness of the stomach has been overcome.

PMID- 28764984
TI  - Broad overview of engineering of functional nanosystems for skin delivery.
AB  - Nanotechnology involves the engineering of functional systems at nanoscale and it
      can be described as a collection of methods and techniques for processing
      materials to create products with special physicochemical properties. The rapid
      developments in nanotechnology have allowed the incorporation of therapeutic
      agents, actives for cosmetic, sensing agents into nanoparticles, for detection,
      prevention, and treatment of skin diseases. Nanoparticles promote the increase of
      penetration of drugs and many cosmetic chemicals across the skin. Nanoparticles
      offer many advantages as carrier systems since they can improve the solubility of
      poorly water-soluble drugs or actives such as phytocompounds, permeate the skin
      through different mechanisms, modify drug or actives pharmacokinetic and
      ultimately, improve their bioavailability. In this review, we discuss the recent
      advances of different types of nanoparticles for skin delivery over a period of
      40 years. This review emphasizes approaches to overcome the drawbacks and
      limitations associated with the conventional systems and the advances and
      application that are poised to further enhance the efficacy of topical
      formulations with nanoparticles, offering the possibility of simplified dosing
      regimen that may improve treatment outcomes using these novel delivery
      nanosystems.

PMID- 28764985
TI  - Function of two ficolin-like proteins in innate immune defense of the oriental
      river prawn, Macrobrachium nipponense.
AB  - Ficolins have crucial functions in recognizing and eliminating pathogens in
      innate immunity. In this study, we identified two ficolin-like genes from the
      oriental river prawn, Macrobrachium nipponense. These genes were designated as
      MnFico1 and MnFico2. MnFico1 cDNA has 1600 bp, whereas MnFico2 has 1486 bp. In
      addition to a coiled-coil region or a low complexity region, the two ficolins
      both contained a signal peptide and a fibrinogen-related domain. qRT-PCR results
      showed that the highest expression level of MnFico1 expression was in the gills,
      whereas that of MnFico2 was in the heart. The transcripts of MnFico1 and MnFico2
      could both respond to bacteria challenge. The transcription of
      antilipopolysaccharide factors ALFs (MnALF1 and MnALF2) and crustin genes
      (MnCru4, MnCru5, MnCru6, and MnCru7) was inhibited in the gills of MnFico1 or
      MnFico2 knockdown prawns at 24 h Vibrio parahaemolyticus challenge. Recombinant
      proteins of rMnFico1 and rMnFico2 could bind toward diverse bacteria and
      agglutinate Gram-negative and Gram-positive bacteria with the presence of calcium
      (Ca2+). rMnFico1 and rMnFico2 proteins also have lipopolysaccharide and
      peptidoglycan binding activity. Both recombinant ficolin proteins could help the
      prawn to facilitate the clearance of V. parahaemolyticus in vivo. Our results
      suggested that MnFico1 and MnFico2 might serve as pattern recognition receptors
      in M. nipponense.

PMID- 28764986
TI  - Management of Neurogenic Pulmonary Edema and Differential Hypoxemia in an Adult
      Supported on Venoarterial Extracorporeal Membrane Oxygenation.

PMID- 28764987
TI  - Rapid Ventricular Pacing for Landing Zone Precision During Thoracic Endovascular
      Aortic Arch Repair: A Case Series.

PMID- 28764988
TI  - Argatroban in Thrombocytopenic Patients Sensitized to Circulating Protamine
      Heparin Complexes.

PMID- 28764989
TI  - Pericardial Placement of a Mediport Catheter.

PMID- 28764990
TI  - Reporting the First Subcutaneous ICD Placed in the Immediate Postorthotopic Heart
      Transplant Period for Acute Cellular Rejection-Associated Cardiac Arrest and
      Investigating the Role of Secondary Prevention ICDs in This Population.

PMID- 28764991
TI  - Transcriptional, translational and systemic alterations during the time course of
      osmoregulatory acclimation in two palaemonid shrimps from distinct osmotic
      niches.
AB  - Palaemonid shrimps exhibit numerous adaptive strategies, both in their life
      cycles and in biochemical, physiological, morphological and behavioral
      characteristics that reflect the wide variety of habitats in which they occur,
      including species that are of particular interest when analyzing adaptive
      osmoregulatory strategies. The present investigation evaluates the short- (hours)
      and long-term (days) time courses of responses of two palaemonid shrimps from
      separate yet overlapping osmotic niches, Palaemon northropi (marine) and
      Macrobrachium acanthurus (diadromous, fresh water), to differential salinity
      challenges at distinct levels of structural organization: (i) transcriptional,
      analyzing quantitative expression of gill mRNAs that encode for subunits of the
      Na+/K+-ATPase and V(H+)-ATPase ion transporters; (ii) translational, examining
      the kinetic behavior of gill Na+/K+-ATPase specific activity; and (iii) systemic,
      accompanying consequent adjustment of hemolymph osmolality. Palaemon northropi is
      an excellent hyper-hypo-osmoregulator in dilute and concentrated seawater,
      respectively. Macrobrachium acanthurus is a strong hyper-regulator in fresh water
      and hypo-regulates hemolymph osmolality and particularly [Cl-] in brackish water.
      Hemolymph hyper-regulation in fresh water (Macrobrachium acanthurus) and dilute
      seawater (Palaemon northropi) is underlain by augmented expression of both the
      gill Na+/K+-ATPase and V(H+)-ATPase. In contrast, in neither species is hypo
      regulation sustained by changes in Na+/K+-ATPase mRNA expression levels, but
      rather by regulating enzyme specific activity. The integrated time course of
      Na+/K+- and V(H+)-ATPase expression and Na+/K+-ATPase activity in the gills of
      these palaemonid shrimps during acclimation to different salinities reveals
      versatility in their levels of regulation, and in the roles of these ion
      transporting pumps in sustaining processes of hyper- and hypo-osmotic and
      chloride regulation.

PMID- 28764992
TI  - Impact on GABA systems in monogenetic developmental CNS disorders: Clues to
      symptomatic treatment.
AB  - Animal studies of several single-gene disorders demonstrate that reversing the
      molecular signaling deficits can result in substantial symptomatic improvements
      in function. Focusing on the ratio of excitation to inhibition as a potential
      pathophysiological hallmark, seven single-gene developmental CNS disorders are
      reviewed which are characterized by a striking dysregulation of neuronal
      inhibition. Deficits in inhibition and excessive inhibition are found. The
      examples of developmental disorders encompass Neurofibromatosis type 1, Fragile X
      syndrome, Rett syndrome, Dravet syndrome including autism-like behavior, NONO
      mutation-induced intellectual disability, Succinic semialdehyde dehydrogenase
      deficiency and Congenital nystagmus due to FRMD7 mutations. The
      phenotype/genotype correlations observed in animal models point to potential
      treatment options and will continue to inspire clinical research. Three drugs are
      presently in clinical trials: acamprosate and ganoxolon for Fragile X syndrome
      and SGS-742 for SSADH deficiency. This article is part of the "Special Issue
      Dedicated to Norman G. Bowery".

PMID- 28764993
TI  - Quantitative reassessment of safety limits of tDCS for two animal studies.

PMID- 28764994
TI  - Alexithymia in multiple sclerosis: A systematic review of literature.
AB  - BACKGROUND: Alexithymia is a multidimensional personality construct characterized
      by difficulties identifying and describing one's feelings, and externally
      oriented thinking. Although extensively reported in psychiatric patients, little
      attention has been paid regarding its occurrence and its pathophysiology in the
      context of multiple sclerosis (MS). METHODS: A research was conducted according
      to the PRISMA guidelines aiming to identify original research articles in English
      and French languages about alexithymia in MS. Computerized databases (MEDLINE,
      PubMed, Scopus) were consulted. The key terms used were the following: ('multiple
      sclerosis' OR 'MS') AND ('alexithymia' OR 'alexithymic' OR 'emotion processing'
      OR 'emotion awareness' OR 'Toronto Alexithymia Scale' OR 'Bermond-Vorst
      Alexithymia Questionnaire') AND ('imaging' OR 'neuroimaging' OR 'magnetic
      resonance imaging' or 'MRI'). References of the retrieved papers were scanned
      manually aiming to get additional sources. RESULTS: 14 papers matched the above
      criteria. The prevalence of alexithymia in MS ranges from 10% to 53%. It seems to
      be associated with anxiety, depression, fatigue, and some social cognitive
      aspects. Its relationship with clinical and classical cognitive variables was
      rarely assessed. Finally, only one study has addressed its pathophysiology and
      has suggested an aberrant interhemispheric transfer. CONCLUSION: Admitting the
      prevalence of alexithymia in MS and its potential negative impact on the quality
      of life and interpersonal communication, screening for it is relevant for a
      better management. Its relationship with clinical, emotional and cognitive
      confounders merits to be further evaluated. Large-scale studies, employing
      neuroimaging techniques, are greatly needed in order to disentangle the neural
      underpinnings of this trait in MS.

PMID- 28764996
TI  - Coagulopathy as a predictor of mortality after penetrating traumatic brain
      injury.
AB  - STUDY HYPOTHESIS: Traumatic brain injury (TBI) is a leading cause of mortality
      with penetrating TBI (p-TBI) patients having worse outcomes. These patients are
      more likely to be coagulopathic than blunt TBI (b-TBI) patients, thus we
      hypothesize that coagulopathy would be an early predictor of mortality. METHODS:
      We identified highest-level trauma activation patients who underwent an admission
      head CT and had ICU admission orders from August 2009-May 2013, excluding those
      with polytrauma and anticoagulant use. Rapid thrombelastography (rTEG) was
      obtained after emergency department (ED) arrival and coagulopathy was defined as
      follows: ACT>=128s, KT>=2.5s, angle<=56 degrees , MA<=55mm, LY-30>=3.0% or
      platelet count<=150,000/MUL. Regression modeling was used to assess the
      association of coagulopathy on mortality. RESULTS: 1086 patients with head CT
      scans performed and ICU admission orders were reviewed. After exclusion criteria
      were met, 347 patients with isolated TBI were analyzed-99 (29%) with p-TBI and
      248 (71%) with b-TBI. Patients with p-TBI had a higher mortality (41% vs. 10%,
      p<0.0001) and a greater incidence of coagulopathy (64% vs. 51%, p<0.003). After
      dichotomizing p-TBI patients by mortality, patients who died were younger and
      were more coagulopathic. When adjusting for factors available on ED arrival,
      coagulopathy was found to be an early predictor of mortality (OR 3.99, 95% CI
      1.37, 11.72, p-value=0.012). CONCLUSIONS: This study demonstrates that p-TBI
      patients with significant coagulopathy have a poor prognosis. Coagulopathy, in
      conjunction with other factors, can be used to earlier identify p-TBI patients
      with worse outcomes and represents a possible area for intervention.

PMID- 28764995
TI  - Magnetically responsive microbubbles as delivery vehicles for targeted
      sonodynamic and antimetabolite therapy of pancreatic cancer.
AB  - Magnetically responsive microbubbles (MagMBs), consisting of an oxygen gas core
      and a phospholipid coating functionalised with Rose Bengal (RB) and/or 5
      fluorouracil (5-FU), were assessed as a delivery vehicle for the targeted
      treatment of pancreatic cancer using combined antimetabolite and sonodynamic
      therapy (SDT). MagMBs delivering the combined 5-FU/SDT treatment produced a
      reduction in cell viability of over 50% when tested against a panel of four
      pancreatic cancer cell lines in vitro. Intravenous administration of the MagMBs
      to mice bearing orthotopic human xenograft BxPC-3 tumours yielded a 48.3%
      reduction in tumour volume relative to an untreated control group (p<0.05) when
      the tumour was exposed to both external magnetic and ultrasound fields during
      administration of the MagMBs. In contrast, application of an external ultrasound
      field alone resulted in a 27% reduction in tumour volume. In addition, activated
      caspase and BAX protein levels were both observed to be significantly elevated in
      tumours harvested from animals treated with the MagMBs in the presence of
      magnetic and ultrasonic fields when compared to expression of those proteins in
      tumours from either the control or ultrasound field only groups (p<0.05). These
      results suggest MagMBs have considerable potential as a platform to enable the
      targeted delivery of combined sonodynamic/antimetabolite therapy in pancreatic
      cancer.

PMID- 28764998
TI  - Validation of the PLASMIC score at a University Medical Center.
AB  - BACKGROUND: The PLASMIC score was recently described as a convenient tool for
      predicting ADAMTS13 activity <=10% in patients with possible thrombotic
      thrombocytopenic purpura (TTP), while awaiting the results of this send-out test.
      The purpose of this study was to validate the PLASMIC score at our University
      Medical Center. METHODS: Apheresis records were reviewed from 2008 to 2017 to
      identify patients who received plasma exchange (PLEX) for suspected TTP. The
      ADAMTS13 activity and PLASMIC scoring criteria were recorded, and the PLASMIC
      score was calculated. RESULTS: Of the 41 patients identified, 20 met inclusion
      criteria, of which 7 patients had ADAMTS13 activity <=10%. Intermediate and high
      PLASMIC scores had 100% sensitivity, 46.2% specificity, 50% positive predictive
      value (PPV), and 100% negative predictive value (NPV). CONCLUSION: These results
      are consistent with the original validation study of the PLASMIC score,
      supporting the efficacy of the PLASMIC score and validating its use at our
      institution.

PMID- 28764997
TI  - Effects of Clostridium perfringens iota toxin in the small intestine of mice.
AB  - Iota toxin is a binary toxin solely produced by Clostridium perfringens type E
      strains, and is structurally related to CDT from C. difficile and CST from C.
      spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually
      assumed that associated diseases are mediated by iota toxin, although evidence in
      this regard has not been provided. In the present report, iota toxin intestinal
      effects were evaluated in vivo using a mouse model. Histological damage was
      observed in ileal loops treated with purified iota toxin after 4 h of incubation.
      Luminal iota toxin induced fluid accumulation in the small intestine in a dose
      dependent manner, as determined by the enteropooling and the intestinal loop
      assays. None of these changes were observed in the large intestine. These results
      suggest that C. perfringens iota toxin alters intestinal permeability,
      predominantly by inducing necrosis and degenerative changes in the mucosal
      epithelium of the small intestine, as well as changes in intestinal motility. The
      obtained results suggest a central role for iota toxin in the pathogenesis of C.
      perfringens type E hemorrhagic enteritis, and contribute to remark the importance
      of clostridial binary toxins in digestive diseases.

PMID- 28764999
TI  - Implementing the Canadian Apheresis Registry: A programmer's point of view.
AB  - Many articles in today's medical journals, including this very publication,
      support their findings by providing data collected during the research of their
      selected study. Various terms used include a randomized group of patients,
      outcome data, total counts and averages. Many of these terms are then supported
      by figures and tables depicted by line graphs, bar graphs and histograms. The
      question to answer is how was all this data gathered? The following discussion
      will attempt to explain, in simple terms, how the data entry and collection was
      implemented for the Canadian Apheresis Registry database.

PMID- 28765001
TI  - Comparison of two common adsorption materials for thermal desorption gas
      chromatography - mass spectrometry of biogenic volatile organic compounds.
AB  - Volatile organic compounds (VOCs) are commonly collected from gaseous samples by
      adsorption to materials such as the porous polymer Tenax TA. Adsorbed compounds
      are subsequently released from these materials by thermal desorption (TD) and
      separated then by gas chromatography (GC) with flame ionization (FID) or mass
      spectrometry (MS) detection. Tenax TA is known to be particularly suitable for
      non-polar to semipolar volatiles, however, many volatiles from environmental and
      biological samples possess a rather polar character. Therefore, we tested if the
      polymer XAD-2, which so far is widely used to adsorb organic compounds from
      aqueous and organic solvents, could provide a broader coverage for (semi)polar
      VOCs during gas-phase sampling. Mixtures of volatile compounds covering a wide
      range of volatility (bp. 20-256 degrees C) and different chemical classes were
      introduced by liquid spiking into sorbent tubes with one of the two porous
      polymers, Tenax TA or XAD-2, and analyzed by TD/GC-MS. At first, an internal
      standard mixture composed of 17 authentic standards was used to optimize
      desorption temperature with respect to sorbent degradation and loading time for
      calibration. Secondly, we tested the detectability of a complex standard mixture
      composed of 57 volatiles, most of them common constituents of the body odor of
      mammals. Moreover, the performance of XAD-2 compared with Tenax TA was assessed
      as limit of quantitation and linearity for the internal standard mixture and 33
      compounds from the complex standard mixture. Volatiles were analyzed in a range
      between 0.01-~250ng/tube depending on the compound and material. Lower limits of
      quantitation were between 0.01 and 3 ng+/-<25% RSD (R2>0.9). Interestingly, we
      found different kinetics for compound adsorption with XAD-2, and a partially
      better sensitivity in comparison with Tenax TA. For these analytes, XAD-2 might
      be recommended as an alternative of Tenax TA for TD/GC-MS analysis.

PMID- 28765002
TI  - Determination of ibuprofen enantiomers in breast milk using vortex-assisted
      matrix solid-phase dispersion and direct chiral liquid chromatography.
AB  - A mixture of beta-cyclodextrin (beta-CD) and primary and secondary amine (PSA)
      sorbents was employed for the extraction and quantification of ibuprofen
      enantiomers from human breast milk, combining a vortex-assisted matrix solid
      phase dispersion method (MSPD) and direct chiral liquid chromatography (CLC) with
      ultraviolet detection (UV). The MSPD sample preparation procedure was optimized
      focusing on both the type and amount of dispersion/sorption sorbents and the
      nature of the elution solvent, in order to obtain acceptable recoveries and
      avoiding enantiomer conversion. These MSPD parameters were optimized with the aid
      of an experimental design approach. Hence, a factorial design was used for
      identification of the main variables affecting the extraction process of
      ibuprofen enantiomers. Under optimum selected conditions, MSPD combined with
      direct CLC-UV was successfully applied for ibuprofen enantiomeric determination
      in breast milk at enantiomer levels between 0.15 and 6.0MUgg-1. The proposed
      analytical method also provided good repeatability, with relative standard
      deviations of 6.4% and 8.3% for the intra-day and inter-day precision,
      respectively.

PMID- 28765000
TI  - Advances in microscale separations towards nanoproteomics applications.
AB  - Microscale separation (e.g., liquid chromatography or capillary electrophoresis)
      coupled with mass spectrometry (MS) has become the primary tool for advanced
      proteomics, an indispensable technology for gaining understanding of complex
      biological processes. In recent decades significant advances have been achieved
      in MS-based proteomics. However, the current proteomics platforms still face an
      analytical challenge in overall sensitivity towards nanoproteomics applications
      for starting materials of less than 1MUg total proteins (e.g., cellular
      heterogeneity in tissue pathologies). Herein, we review recent advances in
      microscale separation techniques and integrated sample processing strategies that
      improve the overall sensitivity and proteome coverage of the proteomics workflow,
      and their contributions towards nanoproteomics applications.

PMID- 28765003
TI  - Socioeconomic risk factors for cholera in different transmission settings: An
      analysis of the data of a cluster randomized trial in Bangladesh.
AB  - BACKGROUND: Cholera remains a threat globally, and socioeconomic factors play an
      important role in transmission of the disease. We assessed socioeconomic risk
      factors for cholera in vaccinated and non-vaccinated communities to understand
      whether the socioeconomic risk factors differ by transmission patterns for
      cholera. METHODS: We used data from a cluster randomized control trial conducted
      in Dhaka, Bangladesh. There were 90 geographic clusters; 30 in each of the three
      arms of the study: vaccine (VAC), vaccine plus behavioural change (VBC), and non
      intervention. The data were analysed for the three populations: (1) vaccinees in
      the vaccinated communities (VAC and VBC arms), (2) non-vaccinated individuals in
      the vaccinated communities and (3) all individuals in the non-vaccinated
      communities (non-intervention arm). A generalized estimating equation with logit
      link function was used to evaluate the risk factors for cholera among these
      different populations adjusting for household level correlation in the data.
      RESULTS: A total of 528 cholera and 226 cholera with severe dehydration (CSD) in
      268,896 persons were observed during the two-year follow-up. For population 1,
      the cholera risk was not associated with any socioeconomic factors; however CSD
      was less likely to occur among individuals living in a household having <=4
      members (aOR=0.55, 95% CI=0.32-0.96). Among population 2, younger participants
      and individuals reporting diarrhoea during registration were more likely to have
      cholera. Females and individuals reporting diarrhoea during registration were at
      increased risk of CSD. Among population 3, individuals living in a household
      without a concrete floor, in an area with high population density, closer to the
      study hospital, or not treating drinking water were at significantly higher risk
      for both cholera and CSD. CONCLUSION: The profile of socioeconomic factors
      associated with cholera varies by individuals' vaccination status as well as the
      transmission setting. In a vaccinated community where transmission would be
      expected to be lower, socioeconomic factors may not increase the risk of the
      disease.

PMID- 28765004
TI  - FDA licensure of and ACIP recommendations for vaccines.
AB  - Many healthcare providers are not familiar with the Food and Drug Administration
      (FDA) vaccine licensure process, the Advisory Committee on Immunization Practices
      (ACIP) vaccine recommendation process, and how FDA vaccine licensure and ACIP
      recommendations are related. Vaccines for use in the United States military and
      civilian populations are licensed by the FDA by several potential pathways but
      use of licensed vaccines in the civilian population should be based on
      recommendations made by the ACIP. In performing these distinct activities, FDA
      and ACIP function under different mandates. In this article, we discuss whether
      the FDA licensure pathways used to approve a vaccine impacts ACIP recommendation
      categories for vaccines licensed from 2006 to 2016.

PMID- 28765005
TI  - Global burden of diarrheal diseases among children in developing countries:
      Incidence, etiology, and insights from new molecular diagnostic techniques.
AB  - The Global Enteric Multicenter Study (GEMS) demonstrated that Shigella and
      enterotoxigenic Escherichia coli (ETEC) producing heat stable toxin (ST) (either
      alone or in combination with heat labile toxin) are among the most important
      pathogens associated with moderate-to-severe diarrhea (MSD) in children younger
      than 5years of age living in developing countries. To inform the design of
      vaccines and other interventions, we reviewed published data and new results from
      GEMS characterizing the burden of Shigella and ST-ETEC infections. Clinical
      parameters were assessed to examine the value of various case definitions as
      indicators of MSD associated with Shigella and ST-ETEC for use in clinical
      trials. We discussed advantages and disadvantages of culture-based and culture
      independent molecular diagnostics for detecting clinically and epidemiologically
      relevant disease. Shigella serotyping data from GEMS were examined to identify
      desirable components of Shigella and ETEC vaccines likely to confer broad
      protection. These findings can inform the development and implementation of
      vaccines to prevent these important infections among infants and children in
      developing countries.

PMID- 28765007
TI  - Combined intravenous, topical and oral tranexamic acid administration in total
      knee replacement: Evaluation of safety in patients with previous thromboembolism
      and effect on hemoglobin level and transfusion rate.
AB  - BACKGROUND: The aims of this study were to investigate the safety of combined
      intravenous, oral and topical tranexamic acid (TXA) in primary total knee
      replacement. We assessed dose-related efficacy on hemoglobin level, transfusion,
      length of stay and thromboembolic complications. In addition, TXA safety in
      patients with previous history of thromboembolism >12months ago was monitored
      specifically. METHODS: From January 2013 until January 2016, 922 patients were
      included who received TXA after primary total knee replacement. Patients without
      TXA administration or with thromboembolic events <12months ago were excluded. TXA
      dosage groups were divided into <=10mg/kg, >10-25mg/kg and >25-50mg/kg. RESULTS:
      Between the three TXA groups no significant difference was found in
      thromboembolic complications (deep venous thrombosis (DVT) and pulmonary embolism
      (PE)), wound leakage and transfusion rate. For patients with DVT or PE in their
      history >12months ago specifically, no more complications were noted in higher
      TXA-dosage groups compared to the low-dosage group. Length of stay was shorter in
      the highest-TXA-dosage group compared with lower-dosage groups (median two vs
      three days). With high TXA dose a smaller difference between pre- and
      postoperative Hb was found: the >25-50mg/kg TXA group had a 0.419mmol/l smaller
      decrease in postoperative hemoglobin compared to the lowest-dosage group
      (P<0.05). CONCLUSION: Combined intravenous, oral and topical TXA is effective in
      knee replacement and can safely be given to patients with a thromboembolic
      history >12months ago. High dosage (>25-50mg/kg) TXA resulted in the smallest
      decrease in postoperative hemoglobin.

PMID- 28765006
TI  - Rationale, design, and implementation of a clinical trial of a mindfulness-based
      relapse prevention protocol for the treatment of women with comorbid post
      traumatic stress disorder and substance use disorder.
AB  - Comorbid post-traumatic stress disorder (PTSD) and substance use disorders (SUD)
      commonly co-occur and is associated with a more complex clinical presentation
      with poorer clinical outcomes when compared with either disorder alone, and
      untreated PTSD can predict relapse to substance abuse. A number of integrated
      treatment approaches addressing symptoms of both PTSD and SUD concurrently
      demonstrate that both disorders can safely and effectively be treated
      concurrently. However, attrition and SUD relapse rates remain high and there is
      need to further develop new treatment approaches. Innovative approaches such as
      mindfulness meditation (MM) successfully used in the treatment of SUD may offer
      additional benefits for individuals with SUD complicated with PTSD. Specifically,
      Mindfulness-based Relapse Prevention (MBRP) integrates coping skills from
      cognitive-behavioral relapse prevention therapy with MM practices, raising
      awareness of substance use triggers and reactive behavioral patterns, and
      teaching skillful coping responses. Here we present the design and methods for
      the "Mindfulness Meditation for the Treatment of Women with comorbid PTSD and
      SUD" study, a Stage 1b behavioral development study that modifies MBRP treatment
      to address both PTSD and SUD in a community setting. This study is divided into
      three parts: revising the existing evidence-based manual, piloting the
      intervention, and testing the new manual in a randomized controlled pilot trial
      in women with comorbid PTSD and SUD enrolled in a community-based SUD treatment
      program.

PMID- 28765008
TI  - Microcystin-leucine arginine exhibits immunomodulatory roles in testicular cells
      resulting in orchitis.
AB  - Microcystin-leucine arginine (MC-LR) causes testicular inflammation and hinders
      spermatogenesis. However, the molecular mechanisms underlying the immune
      responses to MC-LR in the testis have not been elucidated in detail. In this
      study, we show that MC-LR induced immune responses in Sertoli cells (SC), germ
      cells (GC), and Leydig cells (LC) via activating phosphatidylinositol 3-kinase
      (PI3K)/AKT/nuclear factor kappa B (NF-kappaB), resulting in the production of pro
      inflammatory cytokines and chemokines including tumor necrosis factor alpha (TNF
      alpha), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and
      chemokine (C-X-C motif) ligand 10 (CXCL10). The observed effects were attributed
      to reduced activity of protein phosphatases 2A (PP2A) as a result of binding of
      MC-LR to the catalytic subunit of PP2A in SC and GC. By contrast, innate immune
      responses were triggered by Toll-like receptor 2 (TLR2) in LC because MC-LR could
      not enter into the LC and subsequently inhibit the PP2A activity. PI3K/AKT/NF
      kappaB were also activated in SC, GC, and LC in vivo, with the enrichment of TNF
      alpha, IL-6, MCP-1, and CXCL10 in the testis. Following chronic exposure, MC-LR
      treated mice exhibited decreased sperm counts and abnormal sperm morphology. Our
      data demonstrate that MC-LR can activate innate immune responses in testicular
      cells, which provides novel insights to explore the mechanism associated with MC
      LR-induced orchitis.

PMID- 28765009
TI  - Involvement of tRNAs in replication of human mitochondrial DNA and modifying
      effects of telomerase.
AB  - Overexpression of telomerase has been shown to significantly increase the
      lifespan of mice. When mechanistically attributed to repair of critically short
      telomeres, the lifespan extending action of telomerase cannot be reconciled with
      the observation that telomerase-null mice do not exhibit shortening of lifespan
      for at least two generations. We hypothesized that telomerase may interfere with
      replication of mitochondrial DNA (mtDNA) in a way that reduces formation of
      deletions - the primary cause of age-dependent cell attrition in non-renewable
      cells such as myocytes and neurons. Here we show that several tRNA genes may
      function as alternative origins of replication (ORIs). We also show that
      telomerase interacts with canonical light strand ORI (ORIL) and tRNAs and
      modifies their activities. Our results suggest that replication of mitochondrial
      DNA (mtDNA) proceeds through a variety of mechanisms resulting in a mixture of
      classic strand-displacement mode, and coupled replication of heavy and light
      strands. Our results also suggest that effects of telomerase may arise from
      binding ORIL and thus limiting contribution of the deletion-prone strand
      displacement mode to mtDNA synthesis. These findings imply that it may be
      possible to uncouple detrimental and beneficial effects of telomerase, and
      thereby to improve telomerase-based strategies to extend lifespan.

PMID- 28765010
TI  - Balancing Risks in Prostate-specific Antigen Recurrence: The Fox Versus the
      Hedgehog.

PMID- 28765011
TI  - Hyperpolarized 1-[13C]-Pyruvate Magnetic Resonance Imaging Detects an Early
      Metabolic Response to Androgen Ablation Therapy in Prostate Cancer.

PMID- 28765012
TI  - Chemical constituents from the rare mushroom Calvatia nipponica inhibit the
      promotion of angiogenesis in HUVECs.
AB  - Calvatia species, also known as puffball mushrooms, are common sources of food
      worldwide. Calvatia nipponica (Agaricaceae) is one of the most rare species in
      the Calvatia genus. It was first validated in 2008. Due to its scarcity, C.
      nipponica has never been chemically investigated. Its recent discovery in Korea
      allowed to conduct this study, and using bioactivity-guided fractionation for
      antiangiogenic activity, chemical investigation of the MeOH extract of the
      fruiting bodies of C. nipponica led to the isolation of five alkaloids (1-5) and
      two phenolic compounds (6-7). This is the first study to report the chemical
      investigation of C. nipponica, and compound 1 was previously reported as
      chemically synthesized only until our report of its isolation and identification
      from natural sources. The structure of 1 was determined by spectroscopic analysis
      by 1D and 2D NMR spectra and HR-MS. All compounds (1-7) were tested for
      inhibition of angiogenesis using human umbilical vein endothelial cells (HUVECs).
      Compounds 2, 4 and 5 significantly inhibited the promotion of angiogenesis in
      HUVECs. Compound 5 showed the most potent inhibition via downregulation of VEGF,
      p38 and ERK signaling pathways. These results suggested that the rare mushroom C.
      nipponica might be beneficial in antiangiogenesis therapy for cancer treatment.

PMID- 28765013
TI  - Structure-based design, synthesis and in vitro antiproliferative effects studies
      of novel dual BRD4/HDAC inhibitors.
AB  - Histone acetylation marks play important roles in controlling gene expressions
      and are removed by histone deacetylases (HDACs). These marks are read by
      bromodomain and extra-terminal (BET) proteins, whose targeted inhibitors are
      under clinical investigation. BET and HDAC inhibitors have been demonstrated to
      be synergistically killing in Mycinduced murine lymphoma. Herein, we combine the
      inhibitory activities of BET and HDAC into one molecule through structure-based
      design method and evaluate its function. The majority of these synthesized
      compounds showed inhibitory activity against second bromdomains(BRD) of BRD4 and
      HDAC1. Among them, 16ae presented anti-proliferative effects against human acute
      myelogenous leukemia (AML) cell lines in vitro, and 16ae is confirmed to reduce
      the expression of Myc by Western blot analysis. Those results indicated that 16ae
      is a potent dual BRD4/HDAC inhibitor and deserves further investigation.

PMID- 28765014
TI  - Follow-up on Small Abdominal Aortic Aneurysms Using Three Dimensional Ultrasound:
      Volume Versus Diameter.
AB  - OBJECTIVES: Rupture risk in abdominal aortic aneurysms (AAAs) is assessed using
      AAA diameter; yet 10% of ruptures occur in a small aneurysm. This underlines the
      inadequacy of diameter as a standalone parameter. In this prospective follow-up
      study, ultrasound determined aneurysm diameter was compared with aneurysm volume
      determined by three dimensional ultrasound (3D-US) in a group of 179 AAAs.
      DESIGN: This was a prospective cohort study with repeated diameter and volume
      measurements by 3D-US. MATERIAL AND METHODS: In total, 179 patients with small
      infrarenal AAAs (diameter 30-55 mm) were enrolled consecutively. At enrolment and
      at 12 month follow-up, maximum diameter, using dual plane technique, and three
      dimensional volume were measured. Based on a previous accuracy study, significant
      change in diameter and volume were defined as an increase exceeding the known
      range of variability (ROV) of each US technique; +/-3.7 mm and +/-8.8 mL,
      respectively. Post-hoc Kaplan-Meier analysis was performed to estimate time to
      conversion to treatment after the conclusion of the follow-up period between two
      groups. RESULTS: In total, 125 patients (70%) had an unchanged diameter during
      follow-up. In this group, 50 patients (40%) had an increasing aortic volume.
      Forty-five (83%) of the 54 patients with an increasing aortic diameter showed a
      corresponding volume increase. During a median follow-up of 367 days (364-380
      days), a mean increase in diameter of 2.7 mm (+/-2.6 mm) and a mean increase in
      volume of 11.6 mL (+/-9.9 mL) were recorded. In post-hoc analysis, it was found
      that more AAAs with a stable diameter and a growing volume than AAAs with a
      stable diameter and volume were undergoing aortic repair during follow-up, based
      on the maximum diameter. CONCLUSION: In this cohort of small AAAs, 40% of
      patients with a stable diameter had an increasing volume at 12 month follow-up.
      From this perspective, 3D-US could have a future supplemental role in AAA
      surveillance programmes.

PMID- 28765015
TI  - The Impact of Compliance with Imaging Follow-up on Mortality After Endovascular
      Abdominal Aortic Aneurysm Repair: A Population Based Cohort Study.
AB  - OBJECTIVE: Compliance with regular imaging follow-up after endovascular aortic
      aneurysm repair (EVAR) is inconsistent, and evidence of benefit from scheduled
      long-term surveillance is limited. This study sought to characterize the
      association between post-EVAR imaging frequency and long-term survival. METHODS:
      Using administrative health databases for the province of Ontario, Canada, a
      cohort of patients was identified who underwent EVAR between 2004 and 2014.
      Minimum appropriate imaging follow-up (MAIFU) was defined as a CT scan or
      ultrasound of the abdomen within 90 days of EVAR as well as every 15 months
      thereafter. Multivariate time to event analyses characterized the association
      between compliance with MAIFU over time and all-cause mortality. RESULTS: 4988
      patients treated by EVAR were identified. Median follow-up was 3.4 years (IQR 2.0
      5.3 years) and 90 day mortality was 1.6%. Among those who survived over 90 days,
      87% (N = 4251 of 4902) underwent at least one CT scan or ultrasound of the
      abdomen within 90 days, but only 58% (N = 2859 of 4902) went on to meet MAIFU
      criteria. Infrequent imaging correlated with lower follow-up by a vascular
      surgeon, but not with infrequent primary care or specialist consultations.
      Consistently meeting MAIFU criteria was associated with a lower risk of death
      when compared with missing the first imaging follow-up within 90 days (HR 0.82,
      95% CI 0.69-0.96, p = .014), or when compared with having first imaging follow-up
      within 90 days but subsequently not meeting MAIFU criteria (HR 0.78, 95% CI 0.68
      0.91, p = .001). A larger proportion of the follow-up period meeting MAIFU
      criteria was associated with a lower risk of death. CONCLUSIONS: These data
      support efforts to improve compliance with imaging surveillance after EVAR.

PMID- 28765016
TI  - A novel biomarker and hepato-protector for acetaminophen-induced liver injury.

PMID- 28765017
TI  - Effect of Stereoscopic Anaglyphic 3-Dimensional Video Didactics on Learning
      Neuroanatomy.
AB  - BACKGROUND: The teaching of neuroanatomy in medical education has historically
      been based on didactic instruction, cadaveric dissections, and intraoperative
      experience for students. Multiple novel 3-dimensional (3D) modalities have
      recently emerged. Among these, stereoscopic anaglyphic video is easily accessible
      and affordable, however, its effects have not yet formally been investigated.
      OBJECTIVE: This study aimed to investigate if 3D stereoscopic anaglyphic video
      instruction in neuroanatomy could improve learning for content-naive students, as
      compared with 2-dimensional (2D) video instruction. METHODS: A single-site
      controlled prospective case control study was conducted at the School of
      Education. Content knowledge was assessed at baseline, followed by the
      presentation of an instructional neuroanatomy video. Participants viewed the
      video in either 2D or 3D format and then completed a written test of skull base
      neuroanatomy. Pretest and post-test performances were analyzed with independent
      Student's t-tests and analysis of covariance. RESULTS: Our study was completed by
      249 subjects. At baseline, the 2D (n = 124, F = 97) and 3D groups (n = 125, F =
      96) were similar, although the 3D group was older by 1.7 years (P = 0.0355) and
      the curricula of participating classes differed (P < 0.0001). Average scores for
      the 3D group were higher for both pretest (2D, M = 19.9%, standard deviation [SD]
      = 12.5% vs. 3D, M = 23.9%, SD = 14.9%, P = 0.0234) and post-test performances
      (2D, M = 68.5%, SD = 18.6% vs. 3D, M = 77.3%, SD = 18.8%, P = 0.003), but the
      magnitude of improvement across groups did not reach statistical significance
      (2D, M = 48.7%, SD = 21.3%, vs. 3D, M = 53.5%, SD = 22.7%, P = 0.0855).
      CONCLUSION: Incorporation of 3D video instruction into curricula without careful
      integration is insufficient to promote learning over 2D video.

PMID- 28765018
TI  - Takotsubo Cardiomyopathy Triggered by Venous Air Embolism During Craniotomy in
      the Sitting Position.
AB  - BACKGROUND: We present a case of stress-induced cardiomyopathy (Takotsubo
      cardiomyopathy) caused by a venous air embolism during a craniotomy performed in
      the sitting position. CASE DESCRIPTION: A 69-year-old woman was admitted to the
      neurosurgical department and scheduled for elective resection of a cerebellar
      metastasis in the sitting position. After craniotomy and opening of the posterior
      fossa, a venous air embolism was detected via transesophageal echocardiography.
      The patient immediately presented with cardiac decompensation with signs of
      takotsubo or stress-induced cardiomyopathy. CONCLUSIONS: Intensivists and
      anesthesiologists in the operating room and in intensive care units need to be
      aware of stress-induced cardiomyopathy as a probably underdiagnosed disease
      entity, especially as management differs significantly from other forms of
      cardiogenic shock. Diagnosis can be accomplished quickly by bedside
      echocardiography, emphasizing the need for availability of this tool and the
      integration of stress-induced cardiomyopathy in diagnostic algorithms in the
      intensive care unit.

PMID- 28765019
TI  - The Resolution of Oculomotor Nerve Palsy Caused by Unruptured Posterior
      Communicating Artery Aneurysms: A Cohort Study and Narrative Review.
AB  - OBJECTIVE: Recovery of oculomotor nerve palsy after microsurgical and
      endovascular treatment has been studied in numerous small series of predominantly
      ruptured aneurysms. Little consideration has been given to the distinction
      between ruptured and unruptured aneurysms. This study examines the influence of
      treatment modality on oculomotor palsy recovery as a result of unruptured
      posterior communicating artery aneurysms. METHODS: Patients who presented between
      2003 and 2015 with an oculomotor palsy secondary to an unruptured posterior
      communicating artery aneurysm were identified from the hospital database. A
      keyword search for "posterior communicating artery aneurysm" and "oculomotor
      nerve palsy OR third nerve palsy" using the PubMed database was performed for the
      narrative review. RESULTS: The cohort study and narrative review identified 15
      and 179 eligible patients, respectively. Surgically treated patients in the
      cohort study did not have a significantly better rate of complete palsy
      resolution than those who had been coiled (P = 0.08). In the review, clipping of
      the aneurysm resulted in a higher rate of complete palsy resolution (70.0%; 95%
      confidence interval [CI], 60.7%-79.3%) than did coiling (46.5%; 95% CI, 36.0%
      57.0%). Patients who presented with an aneurysm <7 mm had a higher rate of
      complete palsy resolution compared with aneurysms >7 mm (68.6%; 95% CI, 57.7%
      79.5% vs. 44.3%; 95% CI, 32.7%-55.9%). Patients presenting with a complete palsy
      (49.4%; 95% CI, 38.6%-60.2%) had a lower rate of recovery than did those with a
      partial palsy (71.4%; 95% CI, 60.2%-82.6%). CONCLUSIONS: In this narrative
      review, surgical clipping of unruptured posterior communicating artery aneurysms
      was associated with a higher rate of associated oculomotor palsy recovery than
      was endovascular treatment.

PMID- 28765020
TI  - Delayed Intracerebral Hemorrhage Secondary to Ventriculoperitoneal Shunt: A
      Retrospective Study.
AB  - BACKGROUND: Postoperative delayed intracerebral hemorrhage (DICH) secondary to
      ventriculoperitoneal (VP) shunt is a rare but severe event. The present study
      aimed to investigate the incidence and risk factors related to DICH after
      placement of the VP shunt. METHODS: The clinical data from 532 patients with VP
      shunt were collected retrospectively. All clinical variables were examined by
      univariate analysis, and a binary logistic regression analysis was performed to
      identify the risk factors related to DICH. RESULTS: DICH occurred in 20 patients,
      from 3 to 10 days after placement of the VP shunt. Univariate analysis showed
      significant differences between the patients with DICH and without DICH with
      respect to age, history of hypertension, history of craniotomy, and features of
      the first computed tomography (CT) scans after placement of the VP shunt (all P <
      0.05). The binary logistic regression analysis showed that age, history of
      craniotomy, and features of first CT scans after placement of the VP shunt were
      independent risk factors for DICH (all P < 0.05). The prognosis for patients with
      DICH was consistent with the hematoma volume and the neurologic status at the
      time of hospital admission (all P < 0.05). CONCLUSIONS: DICH is a rare and
      potentially severe complication secondary to VP shunt, and a repeat of cranial CT
      scans after placement of the VP shunt is recommended. Advanced age, craniotomy
      history, and brain edema around the catheter on the first cranial CT scan after
      placement of the VP shunt served as independent risk factors for DICH. The
      patients with DICH with poor neurologic status at the time of hospital admission
      or large hematoma volume were associated with poor outcome.

PMID- 28765021
TI  - Reevaluation of Classic Posterior Ventricular Puncture Sites Using a 3
      Dimensional Brain Simulation Model.
AB  - OBJECTIVE: To revalidate the craniometric dimensions of classic posterior burr
      holes for ventricular catheter insertion in hydrocephalic patients, based on
      ideal catheter position on a 3-dimensional simulated computed tomography (CT)
      reconstruction model of the ventricles. METHODS: Fifteen patients with
      hydrocephaly underwent multislice, thin-cut CT to geometrically determine the
      Cartesian coordinates of a new point for optimal posterior ventricular
      catheterization. The success rate for ventricular puncture and the thickness of
      brain traversed by the catheter with 3 approaches (Frazier, Keen, and the
      suggested point) were compared. RESULTS: The suggested burr hole point for
      posterior ventricular catheterization is 51 and 57 mm posterior and 58 and 60 mm
      above the external auditory meatus parallel to the orbitomeatal plane on the
      right and left sides, respectively, significantly different from the classical
      Frazier and Keen points. The success rate was 100% for approaches using the
      suggested point and the Frazier point, compared with 83% using the Keen point.
      This 17% difference was marginally significant (P = 0.052). The parenchymal
      mantle for the Frazier point was thicker than that of the suggested point on both
      sides, although the difference was statistically significant only on the right
      side (P = 0.006). The parenchymal mantle was thinner in the Keen approach
      compared with the suggested approach, but the difference was not statistically
      significant. CONCLUSIONS: The use of a suggested burr hole point for posterior
      ventricular catheterization may decrease the amount of parenchymal mantle of the
      brain transgressed by the catheter, and may marginally improve the chance of
      successful posterior ventricular catheterization.

PMID- 28765022
TI  - Recurrent Lumbar Disc Herniation After Tubular Microdiscectomy: Analysis of
      Learning Curve Progression.
AB  - OBJECTIVE: Tubular microdiscectomy has become a staple technique among spine
      surgeons. Yet the associated learning curve, especially its later stages, has not
      been extensively studied. With studies reporting a higher rate of recurrent
      herniation using tubular microdiscectomy, surgeons' level of experience becomes
      of primary importance for the interpretation of such findings. We aimed to
      analyze possible improvements in the later stages of the learning curve and to
      identify factors independently associated with recurrent herniation. METHODS: A
      retrospective study was conducted using prospectively collected data from a
      consecutive cohort of all 1241 patients operated for single-level lumbar disc
      herniation with tubular microdiscectomy by a single surgeon who already had
      extensive experience with this technique. We collected demographic and
      perioperative data and consequently tracked all complications, recurrent
      herniations, and other reoperations. In addition, 495 patients (40%) provided
      complete outcome scores on a numeric rating scale for back and leg pain and the
      Oswestry Disability Index at baseline, 6 weeks, and 12 months postoperatively.
      RESULTS: A decrease in surgical time (P < 0.001) and recurrent herniations was
      observed (P = 0.012) over time. Increased leg pain at 6 weeks was independently
      associated with recurrent herniation (P = 0.01). Fifty-six patients (4.5%)
      experienced ipsilateral recurrent herniation. CONCLUSIONS: Relevant improvements
      in clinical results were seen even after the surgeon had already accumulated
      extensive experience. Any future studies should unambiguously report the level of
      experience of the participating surgeons, possibly including the number of cases
      previously treated using a particular technique.

PMID- 28765023
TI  - Multicenter Retrospective Cohort Study of "Talk and Die" After Traumatic Brain
      Injury.
AB  - BACKGROUND: Patients who "talk and die" after traumatic brain injury (TBI) are
      potentially salvageable. The reported incidences and risk factors for the "talk
      and die" phenomenon are conflicting and do not take into account recent
      improvements in trauma care. The aim of this study was to determine the
      incidences of "talk and die" after TBI in a modern trauma care system, as well as
      associated risk factors. METHODS: We identified patients who experienced TBI
      (abbreviated injury scale 3-5) between 2004 and 2015 who talked on admission
      (i.e., their verbal component on the Glasgow Coma Scale was >=3 on admission)
      using a nationwide trauma registry (the Japan Trauma Data Bank). The end point
      was in-hospital mortality. We compared patients who talked and died with those
      who talked and survived. RESULTS: During the study period, 236,698 patients were
      registered in the database. Of the 24,833 patients who were eligible for
      analysis, 956 (4.0%) patients subsequently died in the hospital. The in-hospital
      mortality rate significantly decreased over the past 12 years. Older age; male
      sex; a higher injury severity score; a lower Glasgow Coma Scale score;
      comorbidities (congestive heart failure, chronic kidney disease, liver cirrhosis,
      and hematologic disorders); hypotension on arrival; subdural hemorrhage;
      contusion; and vault fracture were independently associated with higher in
      hospital mortality. CONCLUSION: Even in modern trauma care systems, some patients
      still talk and die after TBI. We identified certain risk factors in patients with
      TBI that elicit the requirement for close observation, even if these patients
      talk after TBI.

PMID- 28765024
TI  - AMD3100 Accelerates Reendothelialization of Neointima in Rabbit Saccular Aneurysm
      After Flow Diverter Treatment.
AB  - OBJECTIVE: We sought to inspect the role of AMD3100, which acts as an antagonist
      of stromal cell-derived factor-1/CXC chemokine receptor 4 on the formation of
      neointima in rabbit saccular aneurysm after flow diverter (FD) treatment.
      METHODS: Twenty saccular aneurysm models were established by using porcine
      pancreatic elastase. Three weeks later, a Tubridge FD was implanted into the
      saccular aneurysm. All treated models were immediately divided into 2 groups: the
      AMD3100 group was subcutaneously injected with AMD3100 (5 mg/kg per day), while
      the control group received saline. Morphology and thickness of the neointima were
      investigated 2 and 4 weeks after FD treatment, using hard tissue section and
      masson trichrome staining. Scanning electron microscope was used to observe
      endothelial-like cells, and fluorescence quantitative polymerase chain reaction
      was used to determine mRNA expression of neointima biomarkers, such as kinase
      insert domain receptor, VE-cadherin, CD34, and Tie2. RESULTS: Two and 4 weeks
      after FD treatment, the AMD3100 group had more endothelial-like cells than the
      control group in the neointima. Masson trichrome staining showed that the
      neointima in the AMD3100 group was more intact and thicker than that in the
      control group. Furthermore, increased mRNA levels of kinase insert domain
      receptor, VE-cadherin, and Tie2 in the neointima were found in the AMD3100 group
      compared with the control group. CONCLUSIONS: Interval use of AMD3100 promotes
      the formation of neointima in rabbit saccular aneurysm and facilitates the
      endothelialization of the neointima after FD treatment.

PMID- 28765025
TI  - Congenital Malformations of the Central Nervous System in Rural Western Honduras:
      A 6-Year Report on Trends.
AB  - BACKGROUND: Central nervous system (CNS) malformations, including neural tube
      defects (NTDs), are the second most common type of birth defects worldwide and
      are major causes of childhood disability and mortality. We report the first
      analysis of birth prevalence in Western Honduras of CNS malformations including
      NTDs over 6 consecutive years. METHODS: Data from all patients with congenital
      CNS malformations and total live births for the period 2010-2015 were obtained
      through institution and regional registries from all 3 public referral hospitals
      in Western Honduras, representing 67 municipalities. Cases were identified using
      the International Classification of Diseases, Tenth Revision CNS malformation
      codes. Birth prevalence was calculated as cases per 10,000 live births. RESULTS:
      From 123,903 live births, 275 cases of CNS malformations were identified (54%
      females, 58% NTDs). Six-year birth prevalence of CNS malformations was 13.9-31.1.
      Spina bifida variants and anencephaly represented 80% and 19% of reported NTDs,
      respectively. Total 6-year prevalence of NTDs in Western Honduras was 7.0-17.4
      over years studied. In 6 municipalities, average prevalence was >30 (maximum
      49.0). CONCLUSION: This is the first study reporting disease burden of CNS
      malformations in Western Honduras. The nationwide birth prevalence of NTDs in
      rural Honduras may have decreased since the implementation of prenatal health
      policies in 2005. However, we identified regions with unexpectedly elevated
      prevalence, indicating high regional prevalence that could be targeted for
      improved preventive efforts, ultimately decreasing the burden of these
      conditions.

PMID- 28765026
TI  - Passive Smoking Is Not Associated with Risk of Intracranial Aneurysm Rupture in
      Nonsmoking Women.
AB  - BACKGROUND: Active smoking is a major risk factor for intracranial aneurysm
      rupture (IAR); however, little is known about the effects of passive smoking on
      IAR. In China, female passive smoking is widespread and severe. This study aimed
      to assess whether passive smoking is associated with increased risk of IAR among
      nonsmoking women. METHODS: We enrolled and retrospectively analyzed 385
      consecutive female patients with intracranial aneurysms (IAs; 87 ruptured, 298
      unruptured) who were admitted to our center between June 2015 and January 2017.
      Data on female active smoking, passive smoking, and other factors potentially
      influencing IAR were precisely compared between ruptured and unruptured IAs.
      RESULTS: For all aneurysms, when adjusting for potential confounders, current
      smoking was significantly associated with IAR (odds ratio [OR], 3.31; 95%
      confidence interval [CI], 1.08-10.20; P = 0.037). Furthermore, bifurcation
      location (OR, 5.73; 95% CI, 3.27-10.03; P < 0.001) and educational level (OR,
      1.90; 95% CI, 1.10-3.28; P = 0.022) significantly increased the risk of IAR.
      However, for nonsmoking female patients, approximately one fifth of those with
      IAs were affected by passive smoking; however, passive smoking was not
      significantly associated with IAR. The results also showed that bifurcation
      location (OR, 6.21; 95% CI, 3.46-11.15; P < 0.001) and the location of posterior
      circulation (OR, 3.23; 95% CI, 1.31-7.93; P = 0.011) significantly increased the
      risk of IAR. CONCLUSIONS: Although active current smoking was strongly associated
      with aneurysm rupture in female patients, passive smoking was not an independent
      risk factor for aneurysm rupture in nonsmoking women.

PMID- 28765027
TI  - Factors Determining the Outcome in Trigeminal Neuralgia Treated With Percutaneous
      Balloon Compression.
AB  - OBJECTIVE: To analyze 3T magnetic resonance imaging (MRI) findings and clinical
      features of patients with trigeminal neuralgia (TN) who underwent percutaneous
      balloon compression and to determine whether these findings had an impact on
      prognosis of TN. METHODS: A retrospective review of patients with TN who
      underwent percutaneous balloon compression in the Neurosurgery Department at
      Istanbul Faculty of Medicine between January 1, 2007, and January 1, 2016, was
      undertaken. Of 105 patients who underwent percutaneous balloon compression, 27
      patients who received surgical treatment for the first time for typical TN were
      included in the study. Follow-up data, clinical features, and 3T MRI findings
      were analyzed retrospectively. MRI findings and clinical features of patients
      with and without recurrence of TN were compared. The correlation between
      fractional anisotropy (FA) values and recurrence was investigated. RESULTS:
      During follow-up, 9 (33%) patients had recurrence. The patients with recurrence
      had longer duration of symptoms (P = 0.032), higher FA difference (P = 0.042),
      and higher FA difference rate (P = 0.023). A trend toward early recurrence was
      found in patients with higher FA difference rate, although this was not
      significant (P = 0.051, R = 0.319). CONCLUSIONS: Symptom duration was longer and
      microstructural changes were more apparent in patients with recurrence. In
      addition to age, comorbidities, and other clinical and radiographic features,
      symptom duration and FA values obtained with 3T MRI might be valuable information
      in surgical decision making.

PMID- 28765029
TI  - Surgeries for Patients with Tandem Spinal Stenosis in Cervical and Thoracic
      Spine: Combined or Staged Surgeries?
AB  - BACKGROUND: Cervical and thoracic tandem spinal stenosis (ct-TSS) is a rare yet
      challenging degenerative disease. When the diagnosis is made, surgical
      decompression is indicated for both lesions. However, literature about the
      surgical approaches and prognosis of this disease is lacking. METHODS: From March
      2005 to April 2013, 30 patients with ct-TSS and a mean age of 49.8 years were
      recruited. We outlined 2 types of ct-TSS lesions-adjacent and skip lesions. The
      surgical approach for ct-TSS with adjacent lesions was combined cervical and
      thoracic decompression via a single posterior incision; the approach for skip
      lesions was 2-stage sequential cervical and thoracic decompressions. Neurologic
      status was evaluated with the Japanese Orthopaedic Association scale for cervical
      myelopathy. RESULTS: Seventeen patients underwent 1-stage surgery, and 13
      patients underwent the 2-stage procedure. After surgery, 27 patients (90%)
      experienced improvement. Main complications included transient neurologic
      deterioration in 7 patients, dural tears in 14 patients, and new radiculopathy in
      4 patients. Combined and staged groups were comparable in terms of total length
      of decompression, occurrence of perioperative complications, and recovery rate (P
      > 0.05). The average Japanese Orthopaedic Association score increased
      significantly from 9.8 +/- 1.9 to 13.7 +/- 3.0 (P < 0.05), and the average
      recovery rate was 54.4%. CONCLUSIONS: The types of stenotic lesions should be
      considered when planning surgery for patients with ct-TSS. One-stage
      decompression is suitable for patients with adjacent stenotic lesions; staged
      procedures should be considered for other patients.

PMID- 28765031
TI  - Shifts in the light-dark cycle increase unpredictability of the cardiovascular
      system.
AB  - Physiological variables such as heart rate (HR) and blood pressure (BP) exhibit
      long-term circadian rhythms, which can be disturbed by shift work. On the other
      hand, short-term oscillations in HR and BP have a high prognostic value.
      Therefore, we aimed to determine if the short-term variability, complexity and
      entropy of HR and BP would be affected by a regular light/dark (LD) cycle and
      phase delay shifts of the LD cycle, leading to chronodisruption. Telemetry
      monitored rats were exposed first to the regular LD cycle and then to shifts in
      LD for 8weeks. On the basis of long-term HR and BP recording and evaluation, we
      found circadian rhythms in HR and BP variability, complexity and entropy under
      regular LD cycles. Short-term exposure to shifts disturbed circadian rhythms of
      HR and BP variability, complexity and entropy, indicating chronodisruption. The
      power of circadian rhythms was suppressed after 8weeks of phase delay shifts.
      Long-term exposure to shifts increased variability (p=0.007), complexity
      (p<0.001) and dark-time entropy (p=0.006) of HR but not BP. This is the first
      study demonstrating long-term recording and estimation of HR and BP variability,
      complexity and entropy in conscious rats exposed to irregular lighting
      conditions. After long-term phase delay shifts, short-term variability of HR was
      less predictable than in controls. This study suggests that changes in short-term
      HR and BP oscillations induced by long-term shift work can negatively affect
      cardiovascular health.

PMID- 28765030
TI  - Relationship of A1 Segment Hypoplasia with the Radiologic and Clinical Outcomes
      of Surgical Clipping of Anterior Communicating Artery Aneurysms.
AB  - OBJECTIVE: This study aims to assess whether the A1 segment hypoplasia is a risk
      factor for unfavorable radiologic and clinical outcomes of surgical clipping
      anterior communicating artery (ACoA) aneurysm. METHODS: We retrospectively
      reviewed 251 patients with ACoA aneurysm who underwent surgical clipping in
      Beijing Tiantan Hospital between September 2011 and September 2016. Their
      clinical and radiologic features, as well as clinical outcomes, were reviewed. In
      addition, univariate and multivariate logistic regression analysis was performed
      to identify independent risk factors for the postoperative infarction and
      unfavorable clinical outcomes of surgical clipping ACoA aneurysm. RESULTS: The
      incidence of A1 segment hypoplasia was 49.8% (125 of 251 patients). Univariate
      analysis showed that multiple aneurysm (P = 0.025), diameter of aneurysm (P =
      0.040), and A1 segment hypoplasia (P = 0.010) were associated with anterior
      cerebral artery (ACA) territories infarction, and A1 segment hypoplasia (P =
      0.002) is significantly correlated with unfavorable clinical outcomes of surgical
      clipping ACoA aneurysm. Moreover, multivariate analysis showed that multiple
      aneurysm (P = 0.038; odds ratio [OR], 2.571), diameter of aneurysm (P = 0.034;
      OR, 1.097), and A1 segment hypoplasia (P = 0.007; OR, 3.619) were strongly
      independent risk factors for ACA territories infarction. In addition, Hunt and
      Hess scores (P = 0.036; OR, 2.326) and A1 segment hypoplasia (P = 0.002; OR,
      2.873) are significant independent risk factors for unfavorable clinical outcomes
      of surgical clipping ACoA aneurysm. CONCLUSIONS: A1 segment hypoplasia is a
      significant independent risk factor for unfavorable clinical outcomes of surgical
      clipping ACoA aneurysm and ACA infarction after surgery.

PMID- 28765032
TI  - Effect of Nonpharmacologic Pain Control During Examination for Retinopathy of
      Prematurity.
AB  - OBJECTIVES: To examine the effects of infant swaddling with oral administration
      of sucrose, swaddling with oral administration of breast milk, and swaddling with
      oral administration of distilled water (control) on pain perception in premature
      infants during a screening examination for retinopathy of prematurity (ROP).
      DESIGN: A prospective, randomized controlled design was used. SETTING: The
      research was conducted in the NICU of a Level III university hospital in
      Istanbul. PARTICIPANTS: Data were obtained from 87 premature infants (54% female)
      who were less than 32 weeks gestation and 1500 g body weight. METHODS: The
      nonpharmacologic methods of swaddling with orally administered 0.2 ml of 24%
      sucrose, swaddling with orally administered breast milk, and swaddling with
      orally administered distilled water were implemented immediately before the ROP
      examination. The Premature Infant Pain Profile was used to evaluate pain. Means,
      standard deviations, and repeated-measures analysis of variance and one-way
      analysis of variance tests were used to evaluate pain score data. RESULTS: For
      72.4% of the infants, the experimental session was the first time they were
      examined for ROP. No significant differences in Premature Infant Pain Profile
      scores were found across the three groups. CONCLUSION: Infant swaddlings with
      oral administration of sucrose or breast milk were no more effective than
      swaddling with oral administration of distilled water to reduce pain in premature
      infants during ROP examinations.

PMID- 28765028
TI  - Condylar Joint Fusion and Stabilization (by Screws and Plates) in Nontraumatic
      Atlanto-Occipital Dislocation: Technical Report of 2 Cases.
AB  - BACKGROUND: Nontraumatic spontaneous atlanto-occipital dislocation (AOD) is rare.
      In this report, we discuss the technical steps of condylar joint fusion and
      stabilization (by screws and plates) in nontraumatic AOD. To the best of our
      knowledge, it is the first report of such techniques. MATERIAL AND METHODS: A
      young girl and a young man with progressive quadriparesis due to nontraumatic
      spontaneous atlanto-occipital dislocation were managed by microsurgical
      reduction, fusion, and stabilization of the joint by occipital condylar and C1
      lateral mass screw and plate fixation after mobilization of vertebral artery.
      RESULT: In both cases, condylar joints fixation and fusion were done
      successfully. CONCLUSION: Condylar joint stabilization and fusion may be a good
      or alternative option for AOD.

PMID- 28765033
TI  - Assessment of butorphanol-azaperone-medetomidine combination as anesthesia for
      semen collection and evaluation of semen quality in white-tailed deer (Odocoileus
      virginianus).
AB  - The aim of this current study was to evaluate the level of anesthesia produced by
      a combination of butorphanol-azaperone-medetomidine (BAM) for semen collection by
      electroejaculation on captive white-tailed bucks (Odocoileus virginianus). Ten
      male white-tailed deer, weighing 68.2-115.9kg, ranging in age from one to four
      years were randomly selected from housing pens and anesthetized with the BAM drug
      combination at a dose volume of 2.0mL each. Semen was collected from each animal
      using a standard cervid electroejaculation protocol while under BAM anesthesia.
      Physiological data was recorded following induction of anesthesia and during
      semen collection. Collected ejaculates were prepared for analysis using a
      standard extender protocol for cryopreservation. Eleven sperm viability
      parameters were quantified for each sample using a Computerized Assisted Sperm
      Analysis system, including total seminal volume; sperm concentration and total
      sperm number. kinematic parameters of motile spermatozoa were also assessed.
      Results demonstrated that BAM provided an effective plane of anesthesia for
      successful collection of viable sperm. Measured physiological variables of heart
      rate, respiration and body temperature all remained within safe, normal limits.
      Data recorded on semen characteristics from all collected ejaculates correlated
      well with key traits determined to be important for successful fertilization
      through measurement of total semen volume; sperm concentration; total sperm
      number; and kinematic parameters of motile spermatozoa. There were no serious
      adverse events. This field study indicates that BAM anesthesia is suitable for
      semen collection in white-tailed deer.

PMID- 28765034
TI  - Semen quality, antioxidant status and reproductive performance of rabbits bucks
      fed milk thistle seeds and rosemary leaves.
AB  - The study aimed to investigate the effects of milk thistle seeds (MTS) and
      rosemary leaves (RL) both at 5 and 10g/kg diet on reproductive performance, semen
      quality and blood metabolites of rabbit bucks. A total of 35 rabbit bucks were
      randomly distributed into five experimental groups (7 bucks/group). All the
      groups were fed the same basal diet. The 1st group (control) did not have MTS and
      RL in its basal diet. The 2nd and 3rd groups were supplemented with MTS at 5 and
      10g/kg, respectively. The 4th and 5th groups were fed the basal diet supplemented
      with RL at 5 and 10g/kg, respectively. The sperm concentration (SC), total sperm
      output (TSO), live sperm (LS), total live sperm (TLS) and total motile sperm
      (TMS) were significantly greater in the bucks fed MTS at 10 and RL at 5g/kg diet
      than the control group. Bucks fed MTS at 10g/kg diet had higher fertility than
      the control. Also, RL 5g/kg group showed higher testosterone and fertility than
      the control, but the MTS 10g/kg group showed the highest value for both
      parameters. In conclusion, MTS and RL at 10 and 5g/kg, respectively,
      significantly improved the semen quality and the fertility and MTS also increased
      the economic efficiency of rabbit bucks.

PMID- 28765035
TI  - Effects of adding different levels of Glutamine to modified Beltsville extender
      on the survival of frozen rooster semen.
AB  - The aim of the present study was to investigate the effects of l-glutamine on the
      quality of frozen-thawed rooster semen. Semen samples were collected from eight
      mature roosters (Ross 308). After initial semen assessments, samples of adequate
      quality were mixed together and diluted with modified Beltsville extender without
      l-glutamine (control) and supplemented with 2.5, 5, and 7.5mM l-glutamine. Semen
      straws were subjected to cryopreservation and evaluated twice at 15-day
      intervals. After thawing, sperm viability, total and progressive sperm motilities
      were measured by Eosin-Nigrosine and Computer-Aided Sperm Analysis (CASA),
      respectively. The results showed that sperm functions decreased on day 30
      compared to day 15. The extender supplemented with 5mM glutamine improved
      (p<0.05) sperm viability, total and progressive sperm motilities compared to
      other treatments and the control group. The best level of glutamine appeared to
      be 2.5mM, as it provided the highest sperm membrane integrity and the lowest
      level of abnormalities. The results of this study suggest that the addition of
      glutamine to the diluent improves semen quality and using glutamine allows
      rooster sperm to be frozen for longer.

PMID- 28765036
TI  - World Heart Federation Cholesterol Roadmap.
AB  - BACKGROUND: The World Heart Federation has undertaken an initiative to develop a
      series of Roadmaps. OBJECTIVES: The aim of these is to promote development of
      national policies and health systems approaches and identify potential roadblocks
      on the road to effective prevention, detection and management of cardiovascular
      disease (CVD) in low-and middle-income countries (LMIC), and strategies for
      overcoming these. This Roadmap focuses on elevated blood cholesterol, a leading
      risk factor for myocardial infarction, stroke, and peripheral arterial disease.
      METHODS: Through a review of published guidelines and research papers, and
      consultation with a committee composed of experts in clinical management of
      cholesterol and health systems research in LMIC, this Roadmap identifies (1) key
      interventions for primordial, primary and secondary prevention of CVD through
      detection, treatment, and management of elevated cholesterol and familial
      hypercholesterolemia (FH); (2) gaps in implementation of these interventions
      (knowledge-practice gaps); (3) health system roadblocks to treatment of elevated
      cholesterol in LMIC; and (4) potential strategies for overcoming these. RESULTS:
      Despite strong evidence of the importance of cholesterol levels in primary or
      secondary prevention of CVD, and the effectiveness of statin therapy for
      cholesterol lowering and reduction of CVD risk, gaps exist in the detection,
      treatment, and management of high cholesterol globally. Some potential roadblocks
      include poor access to laboratory facilities or trained professionals for
      cholesterol management, low awareness of FH among the general population and
      health professionals, unaffordability of statins for patient households, and low
      awareness of the importance of persistent adherence to lipid-lowering medication.
      Potential solutions include point-of-care testing, provision of free or
      subsidized lipid-lowering medication, and treatment adherence support using text
      message reminders. CONCLUSIONS: Known effective strategies for detection,
      treatment, and management of elevated cholesterol and FH exist, but there are
      barriers to their implementation in many low-resource settings. Priorities for
      health system intervention should be identified at the national level, and the
      feasibility and effectiveness of proposed solutions should be assessed in
      specific contexts. Many solutions proposed in this Roadmap may apply to other
      cardiovascular conditions and present opportunities for integration of CVD care
      in LMIC.

PMID- 28765037
TI  - Vitamin D effects on monocytes' CCL-2, IL6 and CD14 transcription in Addison's
      disease and HLA susceptibility.
AB  - Addison's disease is a rare autoimmune disorder leading to adrenal insufficiency
      and life-long glucocorticoid dependency. Vitamin D receptor (VDR) polymorphisms
      and vitamin D deficiency predispose to Addison's disease. Aim of the current
      study was, to investigate potential anti-inflammatory vitamin D effects on
      monocytes in Addison's disease, focusing on inflammatory CCL-2 and IL6, as well
      on monocyte CD14 markers. Addison's disease is genetically linked to distinct HLA
      susceptibility alleles. Therefore we analyzed, whether HLA genotypes differed for
      vitamin D effects on monocyte markers. CD14+ monocytes were isolated from
      Addison's disease patients (AD, n=13) and healthy controls (HC, n=15) and
      stimulated with 1,25-dihydroxyvitamin D3 and IL1beta as an inflammatory
      stimulant. Cells were processed for mRNA expression of CCL-2, IL6 and CD14 and
      DNA samples were genotyped for major histocompatibility class (MHC) class II
      encoded HLA- DQA1-DQB1 haplotypes. We found a downregulation of CCL-2 after
      vitamin D treatment in IL1beta-stimulated monocytes both from AD patients and HC
      (AD p<0.001; HC p<0.0001). CD14 expression however, was upregulated in both HC
      and AD patients after vitamin D treatment (p<0.001, respectively). HC showed
      higher CD14 transcription level than AD patients after vitamin D treatment
      (p=0.04). Compared to IL1beta-induced inflammation, HC have increased CD14 levels
      after vitamin D treatment (p<0.001), whereas the IL1beta-induced CD14 expression
      of AD patients' monocytes did not change after vitamin D treatment (p=0.8). AD
      patients carrying HLA high-risk haplotypes showed an increased CCL-2 expression
      after IL1beta-induced inflammation compared to intermediate-risk HLA carriers
      (p=0.05). Also HC monocytes' CD14 transcription after IL1beta and vitamin D co
      stimulation differed according to HLA risk profile. We show that vitamin D can
      exert anti-inflammatory effects on AD patients' monocytes which may be modulated
      by HLA risk genotypes.

PMID- 28765038
TI  - Synergistic effect of 1alpha,25-dihydroxyvitamin D3 and 17beta-estradiol on
      osteoblast differentiation of pediatric MSCs.
AB  - Vitamin D is essential for mineral homeostasis and contributes to bone metabolism
      by stimulating osteoblast differentiation of marrow stromal cells (MSCs). In this
      study, we used MSCs from pre-pubertal girls and boys to test the hypothesis that
      1alpha,25(OH)2D and 17beta-estradiol have synergistic effects on these MSCs, and
      what mechanism is involved. With IRB approval, we isolated MSCs from discarded
      excess iliac marrow graft from children undergoing alveolar cleft repair. Plasma
      was available from 8 female (9.3+/-0.2years) and 8 male (9.6+/-0.1years) subjects
      for hormone assays [25(OH)D, total testosterone, 17beta-estradiol, estrone, DHEA
      S, Growth Hormone, IGF-I]. RT-PCR was used for gene expression. Alkaline
      phosphatase (ALP) activity was used to measure osteoblast differentiation at day
      7; alizarin red was used to measure matrix mineralization at day 21. All subjects
      were pre-pubertal based on their hormone levels. Serum 25(OH)D levels ranged from
      13.1 to 26.4ng/mL, with 75% below 20ng/mL. Constitutive gene expression of VDR
      and ERalpha, beta varied from subject to subject with no association with sex or
      serum chemistries. In osteoblastogenic medium, 1alpha,25(OH)2D3 (10nM) increased
      ALP activity by 36% (p<0.05) in MSCs; 10nM of E2 was not stimulatory but the
      combination of 1alpha,25(OH)2D3 and E2 increased ALP 151% (p<0.05 vs. control)
      and by 84.5% (p<0.05 vs. 1alpha,25(OH)2D3 alone). The combination of
      1alpha,25(OH)2D3 and E2 significantly increased mineralization 11-fold, compared
      with either agent alone. Twenty-four hour treatment with 1alpha,25(OH)2D3 (10nM)
      or E2 (10nM) upregulated each other's receptor by as much as 5.8-fold for ERalpha
      and 2.9-fold for the VDR. In summary, 1alpha,25(OH)2D3 stimulated osteoblast
      differentiation and matrix mineralization with MSCs from pre-pubertal subjects,
      with a synergistic effect of E2, mediated by upregulated receptor levels, at
      least in part. These studies add new information about the regulation of human
      osteoblast differentiation, effects of 1alpha,25(OH)2D3 and E2 on MSCs, and the
      importance of vitamin D for skeletal health.

PMID- 28765040
TI  - The cortisol-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 in
      skeletal muscle in the pathogenesis of the metabolic syndrome.
AB  - The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) contributes
      to intracellular glucocorticoid action by converting inactive cortisone to its
      receptor-active form cortisol (11-dehydrocorticosterone and corticosterone in
      mice and rats). The potential role of 11beta-HSD1 in the pathogenesis of the
      metabolic syndrome has emerged over the past three decades. However, the precise
      impact of 11beta-HSD1 in obesity-related diseases remains uncertain. Many studies
      from animal experiments to clinical studies have investigated liver and adipose
      tissue 11beta-HSD1 in relation to obesity and its metabolic disorders including
      insulin resistance. But the relevance of 11beta-HSD1 in skeletal muscle has been
      less extensively studied. On the other hand, skeletal muscle is assumed to be the
      main site of peripheral insulin resistance, but the biological relevance of
      11beta-HSD1 in skeletal muscle is unclear. This mini-review will focus on 11beta
      HSD1 in skeletal muscle and its postulated link to obesity and insulin
      resistance.

PMID- 28765039
TI  - JNK1 as a signaling node in VDR-BRAF induction of cell death in AML.
AB  - Numerous clinical studies of vitamin D, its derivatives or analogs, have failed
      to clearly demonstrate sustained benefits when used for the treatment of human
      malignant diseases. However, given the strong preclinical evidence of anti
      neoplastic activity and the epidemiological associations suggesting that vitamin
      D compounds may have a place in cancer therapy, attempts are continuing to devise
      new approaches to their therapeutic use. This laboratory has developed a strategy
      to enhance the effectiveness of the currently standard therapy of Acute Myeloid
      Leukemia (AML) by the immediate addition of the vitamin D2 analog Doxercalciferol
      combined with the plant polyphenol-derived Carnosic acid to AML cells previously
      treated with Cytarabine (AraC). Enhancement of AML cell death was noted to be
      dependent on VDR and BRAF kinase. Here we document that the stress-related kinase
      JNK is an important additional component of cell death enhancement in this
      protocol. Either the Knock-down or the inhibition of JNK activity reduced the
      enhancement of AraC-induced cell death, and we show that JNK signaling to the
      apoptosis regulator BIM and Caspase executioners of cell death are downstream of
      VDR and BRAF. A clear understanding of the molecular basis for the increased
      efficacy of AraC in the therapy of AML is expected to bring this regimen to a
      clinical trial.

PMID- 28765041
TI  - Evidence for altered osteoclastogenesis in splenocyte cultures from VDR knockout
      mice.
AB  - The indirect action of 1alpha,25(OH)2-vitamin-D3 (1,25D) on the osteoclast
      through stromal signalling is well established. The role of vitamin D in
      osteoclasts through direct 1,25D-VDR signalling is less well known. We showed
      previously that local 1,25D synthesis in osteoclasts modified osteoclastogenesis
      and osteoclastic resorptive activity. In this study, we hypothesised that
      osteoclasts lacking VDR expression would display an enhanced resorptive capacity
      due to the loss of 1,25D signalling. Splenocytes were cultured under osteoclast
      differentiating conditions from mice with global deletion of the Vdr gene (VDRKO)
      and this was compared with age-matched wild-type littermate controls (WT). In
      VDRKO cultures, osteoclastogenesis was reduced, as indicated by fewer TRAP
      positive multinucleated cells at all time points measured (p<0.05) compared to WT
      levels. However, VDRKO osteoclasts demonstrated greater resorption on a per cell
      basis than their WT counterparts. VDRKO cultures expressed greatly increased c
      Fos mRNA compared to WT. In addition, the ratio of expression of the pro
      apoptotic gene Bax to the pro-survival gene Bcl-2 was decreased in VDRKO
      cultures, implying that these osteoclasts may survive longer than WT osteoclasts.
      Our data indicate abnormal osteoclastogenesis due to the absence of Vdr
      expression, consistent with direct effects of vitamin D signalling being
      important for regulating the maturation and resorptive activities of osteoclasts.

PMID- 28765042
TI  - miR-342-3p elevates osteogenic differentiation of umbilical cord mesenchymal stem
      cells via inhibiting Sufu in vitro.
AB  - Human umbilical mesenchymal stem cells (UCMSCs) have been wildly used in tissue
      engineering field as a promising source because of their unlimited and
      noninvasive origin. To selectively induce osteogenic differentiation of UCMSCs,
      it's imperative to understand the regulatory molecular mechanism underlying the
      process of how these cells switch into osteogenic lineage path. We previously
      showed enhanced sonic hedgehog (Shh) signaling pathway upon osteogenic induction
      in mesenchymal stem cells. In this study, miRNA-seq analysis revealed substantial
      Shh-dependent expression of distinct miRNAs, including miR-342-3p, during
      ostogenesis. RT-qPCR confirmed that miR-342-3p was increased at a greater level
      when Shh signaling pathway was activated by N-terminal of Shh ligand compared
      with osteogenic induction alone, in contrast to the decreasing of suppressor-of
      fused protein (Sufu). Consistently, transient overexpressing miR342-3p in UCMSCs
      via miR-342-3p mimics dramatically decreased Sufu, a suppressor of Gli, while
      osteogenic markers, including alkaline phosphate and osteocalcin, were
      upregulated during osteogenic induction, indicating that miR-342-3p might be
      involved in osteogenesis through the Shh signaling pathway. In conclusion, this
      study showed the potential of miR-342-3p as a therapeutic target to promote bone
      regeneration by modulating expression of Sufu in UCMSCs.

PMID- 28765043
TI  - Feruloylserotonin inhibits hydrogen peroxide-induced melanogenesis and apoptosis
      in B16F10 and SK-Mel-2 melanoma cells.
AB  - Feruloylserotonin (FS) is a major bioactive component of safflower seeds, with
      documented strong antibacterial, anti-inflammatory, and free radical scavenging
      activities. Reactive oxygen species (ROS) can strongly induce melanogenesis and
      cell apoptosis. The present study aimed to investigate the ability of FS in
      preventing hydrogen peroxide (H2O2)-induced melanogenesis and cell apoptosis.
      Melanogenesis and apoptotic cell death were induced by transient exposure to H2O2
      in B16F10 and SK-Mel-2 melanoma cells. FS significantly inhibited melanogenesis
      and cell death in both cell lines. FS inhibited H2O2-induced melanin production
      by down-regulating CREB/MITF/TYR signaling via inhibited intracellular cAMP
      accumulation. Additionally, FS induced extracellular regulated kinase activation,
      which led to the degradation of MITF and consequently decreased TYR expression
      and melanin production in H2O2-stimulated cells. Furthermore, FS inhibited H2O2
      induced apoptotic cell death by maintaining mitochondrial membrane potential.
      Therefore, FS might have potential use for cosmetic whitening and as a
      therapeutic agent for hyperpigmentation disorder.

PMID- 28765044
TI  - Hairless controls hair fate decision via Wnt/beta-catenin signaling.
AB  - The hairless (Hr) gene plays a central role in the hair cycle, considering that
      mutations in the gene result in hair loss with the exception of a few vibrissae
      after the first hair growth cycle in both mice and humans. This study examinedthe
      uncommon phenotype and using microarray analyses and functional studies, we found
      that beta-catenin was mediated by Hr. Progenitor keratinocytes from the bulge
      region differentiate into both epidermis and sebaceous glands, and fail to adopt
      the hair keratinocytes fate in the mutant scalp, due to the decreased Wnt/beta
      catenin signaling in the absence of the hairless protein. This may be attributed
      to the dysfunction of normal epithelial-mesenchymal interactions in the hair
      follicle (HF).

PMID- 28765045
TI  - Androgen-responsive circular RNA circSMARCA5 is up-regulated and promotes cell
      proliferation in prostate cancer.
AB  - Prostate cancer (PCa) is one of the most commonly diagnosed cancers in males
      worldwide. Circular RNA (circRNA) is a unique class of RNA transcribed by RNA
      polymerase II characterized by jointing 3' and 5' ends together via exon or
      intron circularization. However, the molecular functions of circRNAs in prostate
      cancer have rarely been explored. In present study, we found circ-SMARCA5 was up
      regulated in prostate cancer samples compared to match normal tissues. We also
      observed circ-SMARCA5 expression was significantly induced after DHT treatment.
      Functional experiments showed circ-SMARCA5 acted as an oncogene in prostate
      cancer by promoting cell cycle and inhibiting cell apoptosis. We thought this
      study provided useful information for exploring circRNAs as potential therapeutic
      and prognostic targets for prostate cancer.

PMID- 28765046
TI  - Identification and characterization of a centrosomal protein, FOR20 as a novel
      S100A6 target.
AB  - S100A6 is a Ca2+-signal transducer that interacts with numerous proteins and
      regulates their biochemical functions. Here we identified a centrosomal protein,
      FOR20 (FOP-related protein of 20 kDa) as a novel S100A6 target by screening
      protein microarrays carrying 19,676 recombinant GST-fused human proteins. Binding
      experiments revealed that S100A6 interacts with the N-terminal region (residues 1
      30) of FOR20 in a Ca2+-dependent manner in vitro and in living cells. Several
      S100 proteins including S100A1, A2, A4, A11, B also exhibited Ca2+-dependent
      interactions with FOR20 as well as S100A6. We found that two distantly related
      centrosomal proteins, FOP and OFD1, also possess N-terminal regions with a
      significant sequence similarity to the putative S100A6-binding site (residues 1
      30) in FOR20 and are capable of binding to S100A6 in a Ca2+-dependent manner.
      Taken together, these results may indicate that S100A6 interacts with FOR20 and
      related centrosomal proteins through a conserved N-terminal domain, suggesting a
      novel Ca2+-dependent regulation of centrosomal function.

PMID- 28765047
TI  - Lysophosphatidic acid directly induces macrophage-derived foam cell formation by
      blocking the expression of SRBI.
AB  - The leading cause of morbidity and mortality is the result of cardiovascular
      disease, mainly atherosclerosis. The formation of macrophage foam cells by
      ingesting ox-LDL and focal retention in the subendothelial space are the
      hallmarks of the early atherosclerotic lesion. Lysophosphatidic acid (LPA), which
      is a low-molecular weight lysophospholipid enriched in oxidized LDL, exerts a
      range of effects on the cardiovascular system. Previous reports show that LPA
      increases the uptake of ox-LDL to promote the formation of foam cells. However,
      as the most active component of ox-LDL, there is no report showing whether LPA
      directly affects foam cell formation. The aim of this study was to investigate
      the effects of LPA on foam cell formation, as well as to elucidate the underlying
      mechanism. Oil red O staining and a Cholesterol/cholesteryl ester quantitation
      assay were used to evaluate foam cell formation in Raw264.7 macrophage cells. We
      utilized a Western blot and RT-PCR to investigate the relationship between LPA
      receptors and lipid transport related proteins. We found that LPA promoted foam
      cell formation, using 200 MUM for 24 h. Meanwhile, the expression of the
      Scavenger receptor BI (SRBI), which promotes the efflux of free cholesterol, was
      decreased. Furthermore, the LPA1/3 receptor antagonist Ki16425 significantly
      abolished the LPA effects, indicating that LPA1/3 was involved in the foam cell
      formation and SRBI expression induced by LPA. Additionally, the LPA-induced foam
      cell formation was blocked with an AKT inhibitor. Our results suggest that LPA
      enhanced foam cell formation is mediated by LPA1/3 -AKT activation and subsequent
      SRBI expression.

PMID- 28765048
TI  - Diabetes Changes Symptoms Cluster Patterns in Persons Living With HIV.
AB  - Approximately 10-15% of persons living with HIV (PLWH) have a comorbid diagnosis
      of diabetes mellitus (DM). Both of these long-term chronic conditions are
      associated with high rates of symptom burden. The purpose of our study was to
      describe symptom patterns for PLWH with DM (PLWH+DM) using a large secondary
      dataset. The prevalence, burden, and bothersomeness of symptoms reported by
      patients in routine clinic visits during 2015 were assessed using the 20-item HIV
      Symptom Index. Principal component analysis was used to identify symptom
      clusters. Three main clusters were identified: (a) neurological/psychological,
      (b) gastrointestinal/flu-like, and (c) physical changes. The most prevalent
      symptoms were fatigue, poor sleep, aches, neuropathy, and sadness. When compared
      to a previous symptom study with PLWH, symptoms clustered differently in our
      sample of patients with dual diagnoses of HIV and diabetes. Clinicians should
      appropriately assess symptoms for their patients' comorbid conditions.

PMID- 28765049
TI  - Caspase-2 is required for skeletal muscle differentiation and myogenesis.
AB  - Caspase activation plays a crucial role in skeletal muscle differentiation. We
      previously found that caspase-2 activity increases during skeletal muscle cell
      differentiation; however, its direct effect on differentiation has not been fully
      investigated. Here, we found that caspase-2 activity transiently increased more
      than two-fold within 24h following induction of differentiation. Both
      pharmacological inhibition and shRNA-mediated knockdown of caspase-2 suppressed
      myogenic differentiation and dramatically impaired myotube formation.
      Furthermore, shRNA-mediated knockdown prevented induction of p21 and altered cell
      cycle profiles. Interestingly, caspase-3 activity was also dramatically reduced
      following caspase-2 inhibition or ablation. Moreover, caspase-2 and p21 were
      localized to the nucleus during early differentiation. Given the nuclear
      localization of caspase-2 and p21, as well as the impairment in p21 induction in
      caspase-2 knockdown cells, we propose that the role of caspase-2 is to regulate
      p21 induction at the onset of differentiation, which may regulate the myogenic
      program. Collectively, these results highlight a novel function for caspase-2 in
      myocyte differentiation and myogenesis.

PMID- 28765050
TI  - Role of ubiquitination and proteolysis in the regulation of pro- and anti
      apoptotic TNF-R1 signaling.
AB  - Tumor Necrosis Factor Receptor 1 (TNF-R1) transmits various intracellular
      signaling cascades leading to diverse biological outcomes, ranging from
      proliferation, differentiation, survival to the induction of various forms of
      cell death (i.e. apoptosis, necrosis, necroptosis). These signaling pathways have
      to be tightly regulated. Proteolysis is an important regulatory mechanism in TNF
      R1 pro-apoptotic as well as anti-apoptotic/pro-inflammatory signaling. Some key
      players in these signaling cascades are known (mainly the caspase-family of
      proteases and a previously unrecognized "lysosomal death pathway" involving
      cathepsins), however the interaction of proteases in the regulation of TNF
      signaling is still enigmatic. Ubiquitination of proteins, both non-degradative
      degradative, which either results in proteolytic degradation of target substrates
      or regulates their biological function, represents another layer of regulation in
      this signaling cascade. We and others found out that the differences in signal
      quality depend on the localization of the receptors. Plasma membrane resident
      receptors activate survival signals, while endocytosed receptors can induce cell
      death. In this article we will review the role of ubiquitination and proteolysis
      in these diverse events focusing on our own contributions to the lysosomal
      apoptotic pathway linked to the subcellular compartmentalization of TNF-R1. This
      article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in
      Pathophysiology edited by Stefan Rose-John.

PMID- 28765051
TI  - How does calcium interact with the cytoskeleton to regulate growth cone motility
      during axon pathfinding?
AB  - The precision with which neurons form connections is crucial for the normal
      development and function of the nervous system. The development of neuronal
      circuitry in the nervous system is accomplished by axon pathfinding: a process
      where growth cones guide axons through the embryonic environment to connect with
      their appropriate synaptic partners to form functional circuits. Despite intense
      efforts over many years to understand how this process is regulated, the complete
      repertoire of molecular mechanisms that govern the growth cone cytoskeleton and
      hence motility, remain unresolved. A central tenet in the axon guidance field is
      that calcium signals regulate growth cone behaviours such as extension, turning
      and pausing by regulating rearrangements of the growth cone cytoskeleton. Here,
      we provide evidence that not only the amplitude of a calcium signal is critical
      for growth cone motility but also the source of calcium mobilisation. We provide
      an example of this idea by demonstrating that manipulation of calcium signalling
      via L-type voltage gated calcium channels can perturb sensory neuron motility
      towards a source of netrin-1. Understanding how calcium signals can be transduced
      to initiate cytoskeletal changes represents a significant gap in our current
      knowledge of the mechanisms that govern axon guidance, and consequently the
      formation of functional neural circuits in the developing nervous system.

PMID- 28765052
TI  - Predictors of Lower Extremity Amputation and Reamputation Associated With the
      Diabetic Foot.
AB  - In the present study, we aimed to identify the comorbidities that would be
      predictive of requiring lower extremity amputation or reamputation for diabetic
      foot wounds. We performed a retrospective review of 132 consecutive patients who
      had undergone lower extremity amputations (110 patients) or reamputations (22
      patients) for diabetic wounds from January 2013 to March 2016. We used
      multivariate logistic regression to calculate the odds ratios (ORs) for
      amputation and reamputation for various comorbidities. The ORs of undergoing
      amputation were greatest for adult males (OR 5.12, 95% confidence interval [CI]
      1.56 to 13.04; p = .05) and those with longer term diabetes (OR 4.22, 95% CI 2.01
      to 12.95; p = .05), wound infection (OR 3.94, 95% CI 1.04 to 9.00; p = .05),
      diabetic neuropathy (OR 3.53, 95% CI 1.07 to 9.11; p = .05), and a positive
      history of smoking (OR 3.04, 95% CI 1.55 to 9.89; p = .05). Similarly, the ORs of
      undergoing reamputation were greatest for adult males (OR 4.06, 95% CI 1.02 to
      12.08; p = .05) and those with longer term diabetes (OR 3.67, 95% CI 1.94 to
      11.42; p = .05), wound infection (OR 3.12; 95% CI 0.9 to 8.32; p = .05), diabetic
      neuropathy (OR 3.01, 95% CI 0.92 to 8.54; p = .05), and a positive history of
      smoking (OR 2.89, 95% CI 1.09 to 9.42; p = .05). The early identification of
      these comorbidities could help determine which patients are most likely to
      require amputation or reamputation.

PMID- 28765053
TI  - Metatarsal Periosteal Plantar Ganglion Cyst Associated With Stress Fracture: A
      Case Report.
AB  - We encountered a rare case of a periosteal ganglion cyst at the plantar aspect of
      the metatarsal that induced a stress fracture in a 77-year-old female. The
      clinical manifestation of the plantar ganglion cyst of the foot was not evident
      because of its location deep beneath the plantar fascia. A pressure cortical
      indentation was detected at the metatarsal neck on the initial radiographs.
      Magnetic resonance imaging showed a stress fracture of the metatarsal with a
      ganglion cyst. The stress fracture was thought to have resulted from several
      factors, including structural weakness due to bony absorption from the ganglion
      cyst, osteoporosis that induced a fragility fracture, and a load-induced fatigue
      fracture. The fracture completely healed following complete resection of the
      ganglion cyst with the surrounding periosteum along with medication for
      osteoporosis. When confirmation of a stress fracture is necessary or when
      presentation of a stress fracture is atypical, magnetic resonance imaging should
      be considered to confirm or rule out any other associated pathologic features.
      Resection of the periosteal ganglion cyst with the surrounding periosteum is
      important to prevent recurrence.

PMID- 28765054
TI  - Validity and Reliability of Turkish Version of Olerud-Molander Ankle Score in
      Patients With Malleolar Fracture.
AB  - The present study was planned to translate and culturally adapt the Olerud
      Molander Ankle Score (OMAS) and assess the validity and reliability of the
      Turkish translation of the OMAS in patients with surgically treated malleolar
      fracture. The OMAS was adapted for use in Turkish by first translating it and
      then back-translating it in accordance with published guidelines. The final
      Turkish version of the OMAS was administered to 91 patients participating in the
      present study. The OMAS questionnaire was repeated 7 days later to assess test
      retest reliability. Spearman's rank correlation analysis was used for each
      question's score and the total score, and the intraclass correlation coefficient
      was calculated for test-retest reliability. The internal consistency of the OMAS
      TR was assessed using Cronbach's alpha. Concurrent validity was evaluated by
      comparing the OMAS with the Foot and Ankle Outcome Score and global self-rating
      function (GSRF). The GSRF has 5 options: very good, good, fair, poor, and very
      poor. These are assessed using a 5-point Likert scale. Before validity analysis,
      the GSRF score was reduced to 3 groups. In the test-retest reliability
      assessment, the OMAS showed high correlation (r = 0.882). The intraclass
      correlation coefficient was 0.942. Cronbach's alpha was 0.762 and 0.731 at days 1
      and 7 (adequate internal consistency). The correlation coefficients versus the 5
      subscales of the Foot and Ankle Outcome Score ranged from r = 0.753 to r = 0.809
      (p = .000) and versus the GSRF was r = -0.794 (p = .000). According to results of
      the present study, the Turkish version of the OMAS demonstrated adequate test
      retest reliability, excellent internal consistency, and evidence of validity for
      Turkish-speaking patients treated surgically for ankle fracture.

PMID- 28765055
TI  - Mitochondrial dysfunction as a trigger of innate immune responses and
      inflammation.
AB  - A growing literature indicates that mitochondria are key participants in innate
      immune pathways, functioning as both signaling platforms and contributing to
      effector responses. In addition to regulating antiviral signaling and
      antibacterial immunity, mitochondria are also important drivers of inflammation
      caused by sterile injury. Much research on mitochondrial control of immunity now
      centers on understanding how mitochondrial constituents released during cellular
      damage simulate the innate immune system. When mitochondrial integrity is
      compromised, mitochondrial damage-associated molecular patterns engage pattern
      recognition receptors, trigger inflammation, and promote pathology in an
      expanding list of diseases. Here, I review the emerging knowledge of
      mitochondrial dysfunction in innate immune responses and discuss how
      environmental exposures may induce mitochondrial damage to potentiate
      inflammation and human disease.

PMID- 28765056
TI  - Predicting brain age with deep learning from raw imaging data results in a
      reliable and heritable biomarker.
AB  - Machine learning analysis of neuroimaging data can accurately predict
      chronological age in healthy people. Deviations from healthy brain ageing have
      been associated with cognitive impairment and disease. Here we sought to further
      establish the credentials of 'brain-predicted age' as a biomarker of individual
      differences in the brain ageing process, using a predictive modelling approach
      based on deep learning, and specifically convolutional neural networks (CNN), and
      applied to both pre-processed and raw T1-weighted MRI data. Firstly, we aimed to
      demonstrate the accuracy of CNN brain-predicted age using a large dataset of
      healthy adults (N = 2001). Next, we sought to establish the heritability of brain
      predicted age using a sample of monozygotic and dizygotic female twins (N = 62).
      Thirdly, we examined the test-retest and multi-centre reliability of brain
      predicted age using two samples (within-scanner N = 20; between-scanner N = 11).
      CNN brain-predicted ages were generated and compared to a Gaussian Process
      Regression (GPR) approach, on all datasets. Input data were grey matter (GM) or
      white matter (WM) volumetric maps generated by Statistical Parametric Mapping
      (SPM) or raw data. CNN accurately predicted chronological age using GM
      (correlation between brain-predicted age and chronological age r = 0.96, mean
      absolute error [MAE] = 4.16 years) and raw (r = 0.94, MAE = 4.65 years) data.
      This was comparable to GPR brain-predicted age using GM data (r = 0.95, MAE =
      4.66 years). Brain-predicted age was a heritable phenotype for all models and
      input data (h2 >= 0.5). Brain-predicted age showed high test-retest reliability
      (intraclass correlation coefficient [ICC] = 0.90-0.99). Multi-centre reliability
      was more variable within high ICCs for GM (0.83-0.96) and poor-moderate levels
      for WM and raw data (0.51-0.77). Brain-predicted age represents an accurate,
      highly reliable and genetically-influenced phenotype, that has potential to be
      used as a biomarker of brain ageing. Moreover, age predictions can be accurately
      generated on raw T1-MRI data, substantially reducing computation time for novel
      data, bringing the process closer to giving real-time information on brain health
      in clinical settings.

PMID- 28765057
TI  - Decoding cognitive concepts from neuroimaging data using multivariate pattern
      analysis.
AB  - Multivariate pattern analysis (MVPA) methods are now widely used in life-science
      research. They have great potential but their complexity also bears unexpected
      pitfalls. In this paper, we explore the possibilities that arise from the high
      sensitivity of MVPA for stimulus-related differences, which may confound
      estimations of class differences during decoding of cognitive concepts. We
      propose a method that takes advantage of concept-unrelated grouping factors, uses
      blocked permutation tests, and gradually manipulates the proportion of concept
      related information in data while the stimulus-related, concept-irrelevant
      factors are held constant. This results in a concept-response curve, which shows
      the relative contribution of these two components, i.e. how much of the decoding
      performance is specific to higher-order category processing and to lower order
      stimulus processing. It also allows separating stimulus-related from concept
      related neuronal processing, which cannot be achieved experimentally. We applied
      our method to three different EEG data sets with different levels of stimulus
      related confound to decode concepts of digits vs. letters, faces vs. houses, and
      animals vs. fruits based on event-related potentials at the single trial level.
      We show that exemplar-specific differences between stimuli can drive
      classification accuracy to above chance levels even in the absence of conceptual
      information. By looking into time-resolved windows of brain activity, concept
      response curves can help characterize the time-course of lower-level and higher
      level neural information processing and detect the corresponding temporal and
      spatial signatures of the corresponding cognitive processes. In particular, our
      results show that perceptual information is decoded earlier in time than
      conceptual information specific to processing digits and letters. In addition,
      compared to the stimulus-level predictive sites, concept-related topographies are
      spread more widely and, at later time points, reach the frontal cortex. Thus, our
      proposed method yields insights into cognitive processing as well as
      corresponding brain responses.

PMID- 28765058
TI  - Changes in cerebral metabolites in type 2 diabetes mellitus: A meta-analysis of
      proton magnetic resonance spectroscopy.
AB  - To investigate whether there were differences and consistent patterns that
      highlight and consolidate the metabolite changes in type 2 diabetes mellitus
      (T2DM), a meta-analysis of proton magnetic resonance spectroscopy (MRS) was
      conducted. PubMed, Web of Science, and Embase databases were searched up to
      August 2016 for collecting the relevant studies. After an inclusion and exclusion
      criteria, the data was extracted. The data was analyzed using Stata software
      v.12.0. The weight mean difference (MD) and 95% confidence interval (CI) were
      used to compare continuous variables. A total of 10 studies (with a total of 244
      T2DM patients and 223 healthy controls) were included. N-Acetyl Aspartate
      (NAA)/creatine (Cr) levels were decreased in the frontal lobe (MD=-0.20, 95%CI=
      0.33 to -0.06, P=0.005) and lenticular nucleus (MD=-0.14, 95%CI=-0.22 to -0.06,
      P=0.001); choline (Cho)/Cr levels were increased in the lenticular nucleus
      (MD=0.15, 95%CI=0.02-0.28, P=0.025); myo-inositol (MI)/Cr levels were increased
      in the in the occipital lobe (MD=0.11, 95%CI=0.02-0.19, P=0.017) and parietal
      lobe (MD=0.16, 95%CI=0.05-0.28, P=0.006); MI levels were increased in the frontal
      white matter (MD=0.52, 95%CI=0.14-0.90, P=0.008). The results of our meta
      analysis indicated that metabolite levels were altered in different regions of
      brain, which may be shown with MRS and caused clinical symptoms in T2DM further.

PMID- 28765059
TI  - Bing-Neel syndrome - Bilateral cavernous sinus lymphoma causing visual failure.
AB  - We report the case of a 68-year-old male with right eye vision loss secondary to
      a compressive optic neuropathy from Waldenstrom macroglobulinaemia relapse in
      both cavernous sinuses. Central nervous system involvement is extremely uncommon
      in lymphoplasmacytic lymphoma. Known as Bing-Neel syndrome, this has not been
      previously reported to present simultaneously in bilateral cavernous sinuses. We
      discuss the pathophysiology, diagnostic and neuroradiological features of Bing
      Neel syndrome. In this case, there was marked clinical and radiological response
      to chemotherapy. As outcomes following treatment for Waldenstrom
      macroglobulinaemia improve, greater awareness of its less common manifestations
      becomes important. Neurosurgical intervention may be indicated to obtain
      histological diagnosis or decompress critical structures.

PMID- 28765060
TI  - Contemporary management and surveillance strategy after shunt or endoscopic third
      ventriculostomy procedures for hydrocephalus.
AB  - The management of hydrocephalus can be challenging even in expert hands. Due to
      acute presentation, recurrence, accompanying complications, the need for urgent
      diagnosis; a robust management plan is an absolute necessity. We devised a novel
      time efficient surveillance strategy during emergency, and clinic follow up
      settings which has never been described in the literature. We searched all
      articles embracing management/surveillance protocol on pediatric hydrocephalus
      utilizing the terms "hydrocephalus follow up" or "surveillance protocol after
      hydrocephalus treatment". The authors present their own strategy based on vast
      experience in the hydrocephalus management at a single institution. The need for
      the diagnostic laboratory testing, age and presentation based radiological
      imaging, significance of neuro-opthalmological exam, and when to consider the
      emergent exploration have been discussed in detail. Moreover, a definitive
      triaging strategy has been described with the help of flow chart diagrams for
      clinicians, and the neurosurgeons in practice. The triage starts from detail
      history, physical exam, necessary labs, radiological imaging depending on the
      presentation, and the age of the child. A quick head CT scan helps after shunt
      surgery while, a FAST sequence MRI scan (fsMRI) is important in post ETV
      patients. The need for neuro-opthalmological exam, and the shunt series stays
      vital in asymptomatic patients during regular follow up.

PMID- 28765061
TI  - Unilateral tongue myokymia - A rare topodiagnostic sign of different clinical
      conditions.
AB  - Myokymia of the tongue is a very rare clinical condition and is much less common
      than facial or focal myokymia of the limbs. Radiation-induced delayed nerve
      damage is a well-known cause of myokymia, but other etiologies i.e. tumor
      recurrence should be considered as a differential diagnosis. We describe a case
      series of neurophysiologically proven unilateral tongue myokymia, which arose in
      two patients after radiotherapy of the neck/head and in one patient due to a
      space occupying meningioma of the cerebrospinal passage affecting the hypoglossal
      nerve. With this case series and a review of the literature we aim to raise
      clinical suspicion of tongue myokymia and highlight the clinical and
      electromyographic impact of myokymia in the diagnosis of malignancies and
      treatment-associated lesions of the hypoglossal nerve.

PMID- 28765063
TI  - Indirect decompression and reduction of lumbar spondylolisthesis does not result
      in higher rates of immediate and long term complications.
AB  - Nerve root decompression and spondylolisthesis reduction is typically reserved
      for open surgery. MIS techniques have been thought to be associated with higher
      rates of neurological complications. This study aims to report acute and chronic
      neurologic complications encountered with MIS surgery for spondylolisthesis,
      specifically, the incidence of nerve root injury and clinical and radiographic
      outcomes. A retrospective review of 269 patients who underwent MIS LIF or ALIF
      treatment for lumbar degenerative or isthmic grade 1 or 2 spondylolisthesis was
      conducted. Immediate and long-term complication rates were the primary outcome.
      Only patients who had symptomatic anterolisthesis and 2-year outcome data were
      included in the study. 52 patients met inclusion criteria with 54 lumbar
      spondylolisthesis levels treated. Five patients (9.6%) experienced postoperative
      anterior thigh numbness, which completely resolved within 3months. There were no
      permanent neurologic deficits; however, 2 patients (3.8%) suffered a transient
      foot weakness that resolved with physical therapy by 3months follow-up. There was
      one incidence of wound breakdown that required revision and one incidence of
      L5/S1 endplate/sacral promontory fracture and relisthesis 3months
      postoperatively. Overall fusion rate was 98% at 6months. Indirect decompression
      and closed anatomical reduction for treatment of low-grade spondylolisthesis
      using ALIF and LIF with posterior percutaneous fixation was not associated with
      an increased risk of neurologic deficit. This study suggests that this technique
      is safe, reproducible, durable, and provides adequate fusion rates.

PMID- 28765062
TI  - Immune mediated neuropathy following checkpoint immunotherapy.
AB  - Checkpoint immunotherapy has revolutionised cancer therapy and is now standard
      treatment for many malignancies including metastatic melanoma. Acute inflammatory
      neuropathies, often labelled as Guillain-Barre syndrome, are an uncommon but
      potentially severe complication of checkpoint immunotherapy with individual cases
      described but never characterised as a group. We describe a case of acute
      sensorimotor and autonomic neuropathy following a single dose of combination
      ipilimumab and nivolumab for metastatic melanoma. A literature search was
      performed, identifying 14 other cases of acute neuropathy following checkpoint
      immunotherapy, with the clinical, electrophysiological and laboratory features
      summarised. Most cases described an acute sensorimotor neuropathy (92%) with
      hyporeflexia (92%) that could occur from induction up till many weeks after the
      final dose of therapy. In contrast to Guillain-Barre syndrome, the cerebrospinal
      fluid (CSF) analysis often shows a lymphocytic picture (50%) and the
      electrophysiology showed an axonal pattern (55%). Treatment was variable and
      often in combination. 11 cases received steroid therapy with only 1 death within
      this group, whereas of the 4 patients who did not receive steroid therapy there
      were 3 deaths. In conclusion checkpoint immunotherapy - induced acute
      neuropathies are distinct from and progress differently to Guillain-Barre
      syndrome. As with other immunotherapy related adverse events corticosteroid
      therapy should be initiated in addition to usual therapy.

PMID- 28765064
TI  - Treatment of epilepsy in patients with myasthenia gravis: Is really harder than
      it looks?
AB  - The relationship between myasthenia gravis (MG) and epilepsy has been rarely
      reported. As consequence, there are no specific guidelines for the management of
      these conditions when they mutually occur. We reported on three patients in whom
      epilepsy and MG are coexisting, but in different clinical settings. Two patients
      were treated with antiepileptic drugs which improved their symptoms. One patient
      has controlled the seizures after a successful anterior temporal lobectomy with
      no appreciable consequences to her MG. We discuss the difficulties in the
      management of epilepsy in patients with MG. In addition, we report on the first
      epileptic surgery in a MG patient, indicating that this surgical procedure as a
      safe option for the treatment of intractable epilepsy in patients with MG.

PMID- 28765065
TI  - Reconstructive outcome of intraoperative cerebrospinal fluid leak after
      endoscopic endonasal surgery for tumors involving skull base.
AB  - Endoscopic transnasal surgery for tumors located at the base of the skull has a
      high incidence of postoperative cerebrospinal fluid (CSF) leaks. Here, we
      assessed the repair outcomes for high-flow CSF leaks based upon the tumor
      location, and analyzed the reasons for repair failure after transnasal endoscopic
      surgery solely for tumors involving the base of the skull. From Feb. 2009 to Dec.
      2014 we performed endoscopic endonasal surgery for a variety of skull base
      lesions in 788 patients at our institution. Among them, 95 patients with
      intradural skull base tumors underwent endoscopic transnasal surgery. We
      performed surgical repairs with a multilayered nonvascularized construct (38
      patients) and a vascularized pedicled nasoseptal flap construct combined with a
      fascia graft (57 patients). Overall, 14 of 95 patients (14.7%) who underwent
      endoscopic transnasal surgery for skull base tumors developed postoperative CSF
      leaks. The major causes of repair failure included graft disruption by a lack of
      counter-pressure in the multilayered non-vascularized technique, and inadequate
      drilling of the sphenoid bone, displacement of the flap due to pressure from CSF
      or gravity, or disruption of flap integrity in the vascularized pedicled flap
      technique. Logistic regression analysis revealed that there was no significant
      association between repair failure and age, sex, type of reconstructive method
      used, and primary tumor type (p>0.05). Reconstruction after endoscopic endonasal
      surgery remained challenging, especially for non-pituitary skull base tumors
      requiring intra-arachnoidal dissection. Recent advances in reconstructive
      techniques require the accumulation of experiences with sufficient dexterity to
      achieve an acceptable morbidity rate.

PMID- 28765066
TI  - Outcomes of Single Stage Phalloplasty by Pedicled Anterolateral Thigh Flap versus
      Radial Forearm Free Flap in Gender Confirming Surgery.
AB  - PURPOSE: Phalloplasty is a critical step in female-to-male (transmale) gender
      confirming genital surgery. We examined outcomes between transmales who underwent
      phalloplasty with vaginectomy and full-length urethroplasty using the
      anterolateral thigh pedicled flap or the radial forearm free flap. MATERIALS AND
      METHODS: We performed a single center, retrospective study of patients who
      underwent phalloplasty with vaginectomy and full-length urethroplasty using an
      anterolateral thigh pedicled flap or a radial forearm free flap from April 2013
      to July 2016. All patients had at least 6 months of followup. Urethral and
      nonurethral complications were recorded. Complication rates were assessed using
      the OR of the anterolateral thigh pedicled flap and the radial forearm free flap
      groups. RESULTS: Of the 213 patients 149 and 64 underwent radial forearm free
      flap and anterolateral thigh pedicled flap phalloplasty, respectively. Patients
      with a radial forearm free flap had a significantly higher body mass index than
      those with an anterolateral thigh pedicled flap. The overall urethral
      complication rate for radial forearm free flap and anterolateral thigh pedicled
      flap phalloplasty was 31.5% and 32.8%, and the rate of partial or total
      neophallus loss was 3.4% and 7.8%, respectively. Patients in the pedicled flap
      cohort experienced significantly greater odds of urethral fistula (OR 2.50, p =
      0.024), nonurethral complications (OR 2.38, p = 0.027) and phallus wound
      dehiscence (OR 5.03, p = 0.026). CONCLUSIONS: Anterolateral thigh pedicled flap
      phalloplasty was associated with overall greater odds of urethral and other
      complications at 6 months of followup. Our findings can help guide surgical
      decision making when selecting a flap for phalloplasty.

PMID- 28765067
TI  - Development and Validation of Objective Performance Metrics for Robot-Assisted
      Radical Prostatectomy: A Pilot Study.
AB  - PURPOSE: We explore and validate objective surgeon performance metrics using a
      novel recorder ("dVLogger") to directly capture surgeon manipulations on the da
      Vinci(r) Surgical System. We present the initial construct and concurrent
      validation study of objective metrics during preselected steps of robot-assisted
      radical prostatectomy. MATERIALS AND METHODS: Kinematic and events data were
      recorded for expert (100 or more cases) and novice (less than 100 cases) surgeons
      performing bladder mobilization, seminal vesicle dissection, anterior
      vesicourethral anastomosis and right pelvic lymphadenectomy. Expert/novice
      metrics were compared using mixed effect statistical modeling (construct
      validation). Expert reviewers blindly rated seminal vesicle dissection and
      anterior vesicourethral anastomosis using GEARS (Global Evaluative Assessment of
      Robotic Skills). Intraclass correlation measured inter-rater variability.
      Objective metrics were correlated to corresponding GEARS metrics using Spearman's
      test (concurrent validation). RESULTS: The performance of 10 experts (mean 810
      cases, range 100 to 2,000) and 10 novices (mean 35 cases, range 5 to 80) was
      evaluated in 100 robot-assisted radical prostatectomy cases. For construct
      validation the experts completed operative steps faster (p <0.001) with less
      instrument travel distance (p <0.01), less aggregate instrument idle time (p
      <0.001), shorter camera path length (p <0.001) and more frequent camera movements
      (p <0.03). Experts had a greater ratio of dominant-to-nondominant instrument path
      distance for all steps (p <0.04) except anterior vesicourethral anastomosis. For
      concurrent validation the median experience of 3 expert reviewers was 300 cases
      (range 200 to 500). Intraclass correlation among reviewers was 0.6-0.7. For
      anterior vesicourethral anastomosis and seminal vesicle dissection, kinematic
      metrics had low associations with GEARS metrics. CONCLUSIONS: Objective metrics
      revealed experts to be more efficient and directed during preselected steps of
      robot-assisted radical prostatectomy. Objective metrics had limited associations
      to GEARS. These findings lay the foundation for developing standardized metrics
      for surgeon training and assessment.

PMID- 28765068
TI  - 5'-tRNA Halves are Dysregulated in Clear Cell Renal Cell Carcinoma.
AB  - PURPOSE: In various malignancies RNA fragments are dysregulated. Our study was
      designed to determine the expression of 4, 5'-tRNA halves in the tissue and serum
      of patients with clear cell renal cell carcinoma. MATERIALS AND METHODS: Tissue
      and serum samples of patients with clear cell renal cell carcinoma and
      nonmalignant disease were collected prospectively in our biobank. We isolated
      total RNA from 95 clear cell renal cell carcinomas and 50 normal renal tissues as
      well as serum RNA from 27 patients with clear cell renal cell carcinoma and 13
      with nonmalignant urological disease. To specifically determine the expression of
      5'-tRNA halves we dephosphorylated and ligated an adaptor nucleotide to the 3'
      end of the tRNA halves. The expression levels of 4, 5'-tRNA halves (5'-tRNA-Arg
      CCT, 5'-tRNA-Glu-CTC, 5'-tRNA-Leu-CAG and 5'-tRNA-Lys-TTT) were then measured by
      TaqMan(r) based quantitative reverse transcription-polymerase chain reaction.
      RESULTS: All studied 5'-tRNA halves were down-regulated in clear cell renal cell
      carcinoma tissues, indicating a potential role as a tumor suppressor.
      Furthermore, we noted decreased expression of 5'-tRNA halves in patients with
      adverse clinicopathological parameters. All 5'-tRNA halves were expressed at
      lower levels in nonorgan confined clear cell renal cell carcinoma. The 5'-tRNA
      Lys-TTT halves inversely correlated with ISUP (International Society of
      Urological Pathology) grade. In patients with clear cell renal cell carcinoma 5'
      tRNA-Arg-CCT, 5'-tRNA-Glu-CTC and 5'-tRNA-Lys-TTT halves circulated at lower
      levels than in control subjects, indicating relevance as noninvasive biomarkers.
      CONCLUSIONS: In patients with clear cell renal cell carcinoma 5'-tRNA halves have
      potential as diagnostic and prognostic biomarkers. The 5'-tRNA halves may act in
      a tumor suppressive manner, which requires further research to confirm.

PMID- 28765069
TI  - Prostate Cancer Screening in Early Medicaid Expansion States.
AB  - PURPOSE: The PPACA (Patient Protection and Affordable Care Act) of 2010 included
      a provision to expand Medicaid by 2014. Six states and jurisdictions elected to
      expand Medicaid early before 2012. This provided a natural experiment to test the
      association between expanded insurance coverage and preventive service
      utilization, including prostate cancer screening. MATERIALS AND METHODS: Using
      the 2012 and 2014 BRFSS (Behavioral Risk Factor Surveillance System) surveys we
      identified men 40 to 64 years old who reported prostate specific antigen testing
      in the preceding 12 months. Sociodemographic and access to care variables were
      extracted. Income was stratified by the relationship to Medicaid eligibility and
      the federal poverty level (less than 138%, 138% to 400% and greater than 400%).
      The weighted prevalence of prostate specific antigen was estimated. Multivariable
      logistic regression models were used to evaluate factors associated with prostate
      specific antigen screening. Interaction analysis for Medicaid expansion was
      performed. RESULTS: Among 158,103 respondents individuals in nonexpansion states
      had the highest incidence of prostate specific antigen screening. Nationally
      screening decreased between 2011 and 2013 (OR 0.87, 95% CI 0.83-0.91). In only
      early expansion states there was a 3% absolute increase in screening among men in
      the less than 138% federal poverty level, which was associated with expansion
      status (pinteraction = 0.04). Increased screening in early expansion states was
      also seen in men who were 55 to 59 years old, nonHispanic African American,
      Hispanic, previously married, not high school graduates and current smokers.
      CONCLUSIONS: Between 2011 and 2013 there were national declines in prostate
      cancer screening. However, there was significant narrowing of the gap in prostate
      specific antigen screening between higher and low income men in Medicaid early
      expansion states. This may reflect improved access to preventive services among
      populations with historic barriers to care.

PMID- 28765070
TI  - Prefrontal connections of the perirhinal and postrhinal cortices in the rat.
AB  - Knowing how prefrontal regions interact with medial temporal lobe structures is
      important for understanding memory and cognition. Using anterograde and
      retrograde tract tracing methods in the rat, we report a detailed study of the
      perirhinal (PER) and postrhinal (POR) connections with the lateral,
      ventrolateral, and medial orbitofrontal cortices (ORBl, ORBvl, ORBm), infralimbic
      and prelimbic cortices (IL, PL), ventral and dorsal anterior cingulate cortices
      (ACAv, ACAd), and secondary motor cortex (MOs). Our analyses included the
      topography and laminar patterns of these connections. The PER and POR showed
      reciprocal connectivity with all prefrontal regions examined, but the patterns of
      connections differed. In general, PER areas 36 and 35 showed patterns of
      connectivity that were more similar to each other than to those of the POR.
      Analysis of anterograde tracers showed that PER areas 36 and 35 provide the
      strongest projections to prefrontal regions. The heaviest fiber labeling was in
      IL and PL, closely followed by orbital regions. Fiber labeling arising from
      injections in POR was weaker overall. The strongest POR efferents targeted MOs,
      ACAv, and ORBvl. For return projections, analysis of retrograde tracers showed
      that PER areas 36 and 35 receive strong inputs from orbitofrontal and medial
      prefrontal regions. Interestingly, PER also received substantial inputs from MOs
      and ACAd. The POR receives a very strong input from MOs, followed by ACAd, and
      ORBvl. Based on comparison of our findings with those obtained in monkeys, we
      argue that the rodent ACAd and MOs may be a functional homolog of the primate
      dorsolateral prefrontal cortex.

PMID- 28765071
TI  - FICZ generates human tDCs that induce CD4+ CD25high Foxp3+ Treg-like cell
      differentiation.
AB  - Dendritic cells (DCs) play a central role in the maintenance of immune
      homeostasis, their participation as professional antigen presenting cells is
      essential to the initiation of the adaptive immune response as well as to the
      induction of tolerance. The recently described role of the aryl hydrocarbon
      receptor (AhR) in the immune system, particularly in the modulation of the
      adaptive immune response has attracted the attention as a potential player in the
      induction of immune tolerance. However, the effects of AhR activation through
      endogenous ligands on human DCs have been poorly evaluated. In this study, we
      investigated the effect of FICZ, a natural AhR ligand, on monocyte-derived
      dendritic cells (Mo-DCs) from healthy subjects. We found that the activation of
      AhR through FICZ during DCs differentiation and maturation processes resulted in
      a decreased expression of CD83, an increased expression of the enzyme IDO and a
      reduced production of the pro-inflammatory cytokines IL-6 and TNF-alpha. More
      importantly, FICZ-treated DCs were able to induce the differentiation of naive T
      lymphocytes into CD4+ CD25high Foxp3+ T reg-like cells. Our results show that the
      activation of the AhR on human DCs induces a tolerogenic phenotype with potential
      implications in immunotherapy.

PMID- 28765072
TI  - Poor recovery from a pulmonary exacerbation does not lead to accelerated FEV1
      decline.
AB  - BACKGROUND: Patients with CF treated for pulmonary exacerbations (PEx) may
      experience faster subsequent declines in FEV1. Additionally, incomplete recovery
      to baseline FEV1 occurs frequently following PEx treatment. Whether accelerated
      declines in FEV1 are preceded by poor PEx recovery has not been studied. METHODS:
      Using 2004 to 2011 CF Foundation Patient Registry data, we randomly selected one
      PEx among patients >=6years of age with no organ transplantations, >=12months of
      data before and after the PEx, and >=1 FEV1 recorded within the 6months before
      and 3months after the PEx. We defined poor PEx recovery as the best FEV1 in the
      3months after the PEx <90% of the best FEV1 in the 6months before the PEx. We
      calculated mean (95% CI) hazard ratios (HR) of having >5% predicted/year FEV1
      decline and poor PEx recovery using multi-state Markov models. RESULTS: From
      13,954 PEx, FEV1 declines of >5% predicted/year were more likely to precede poor
      spirometric recovery, HR 1.17 (1.08, 1.26), in Markov models adjusted for age and
      sex. Non-Responders were less likely to have a subsequent fast FEV1 decline, HR
      0.41 (0.37, 0.46), than patients who recovered to >90% of baseline FEV1 following
      PEx treatment. CONCLUSIONS: Accelerated declines in FEV1 are more likely to
      precede a PEx with poor recovery than to occur in the following year. Preventing
      or halting declines in FEV1 may also have the benefit of preventing PEx episodes.

PMID- 28765073
TI  - Strain differences in intermale aggression and possible factors regulating
      increased aggression in Japanese quail.
AB  - The National Institute for Environmental Studies (NIES) of Japan established a
      strain of Japanese quail (Coturnix japonica) known as NIES-L by rotation breeding
      in a closed colony for over 35years; accordingly, the strain has highly inbred
      like characteristics. Another strain called NIES-Brn has been maintained by
      randomized breeding in a closed colony to produce outbred-like characteristics.
      The current study aimed to characterize intermale aggressive behaviors in both
      strains and to identify possible factors regulating higher aggression in the
      hypothalamus, such as sex hormone and neuropeptide expression. Both strains
      displayed a common set of intermale aggressive behaviors that included pecking,
      grabbing, mounting, and cloacal contact behavior, although NIES-Brn quail showed
      significantly more grabbing, mounting, and cloacal contact behavior than did NIES
      L quail. We examined sex hormone levels in the blood and diencephalon in both
      strains. Testosterone concentrations were significantly higher in the blood and
      diencephalon of NIES-Brn quail compared to NIES-L quail. We next examined gene
      expression in the hypothalamus of both strains using an Agilent gene expression
      microarray and real-time RT-PCR and found that gene expression of mesotocin (an
      oxytocin homologue) was significantly higher in the hypothalamus of NIES-Brn
      quail compared to NIES-L quail. Immunohistochemistry of the hypothalamus revealed
      that numbers of large cells (cell area>500MUm2) expressing mesotocin were
      significantly higher in the NIES-Brn strain compared to the NIES-L strain. Taken
      together, our findings suggest that higher testosterone and mesotocin levels in
      the hypothalamus may be responsible for higher aggression in the NIES-Brn quail
      strain.

PMID- 28765074
TI  - Estrogenic effects associated with bisphenol a exposure in male zebrafish (Danio
      rerio) is associated with changes of endogenous 17beta-estradiol and gene
      specific DNA methylation levels.
AB  - The binding affinity of bisphenol A (BPA) to estrogen receptors (ERs) is much
      lower than that of 17beta-estradiol (E2), and whether there are other molecular
      mechanisms responsible for the estrogenic action of BPA in vivo currently remains
      unknown. The objective of this study was to explore the potential association
      between the estrogenic effect induced by bisphenol A in vivo and changes of
      endogenous E2 and gene specific DNA methylation levels. After a waterborne
      exposure of male zebrafish to 500, 1000, or 1500MUg/L of BPA for 21d,
      vitellogenin (VTG) concentration in whole body homogenate, plasma E2 and
      testosterone levels, hepatic ERs mRNA expressions, gonadal cyp19a1a and cyp17a1
      mRNA expressions, and methylation levels of hepatic esr1 and gonadal cyp19a1a's
      promoters were determined. Our results indicated that for the 500 and 1500MUg/L
      treatment groups, VTG might be induced mainly by the elevated E2 levels;
      increases of E2 levels could be partly explained by the up-regulated expression
      of gonadal aromatase, mRNA levels of which were found to be negatively related to
      the methylation levels of both its promoter and one CpG site. In addition, upon
      BPA exposure, hepatic esr1 mRNA levels were also negatively related to the
      methylation levels of both its promoter and one CpG site. These observations
      provide evidence for the non-ERs mediated mechanisms underlying the estrogenic
      action of BPA on male zebrafish.

PMID- 28765075
TI  - Parkinson's disease-associated pathogenic VPS35 mutation causes complex I
      deficits.
AB  - Defect in the complex I of the mitochondrial electron-transport chain is a
      characteristic of Parkinson's disease (PD) which is thought to play a critical
      role in the disease pathogenesis. Mutations in vacuolar protein sorting 35
      (VPS35) cause autosomal dominant PD and we recently demonstrated that pathogenic
      VPS35 mutations cause mitochondrial damage through enhanced mitochondrial
      fragmentation. In this study, we aimed to determine whether pathogenic VPS35
      mutation impacts the activity of complex I and its underlying mechanism. Indeed,
      VPS35 D620N mutation led to decreased enzymatic activity and respiratory defects
      in complex I and II in patient fibroblasts. While no changes in the expression of
      the complex I and II subunits were noted, the level of assembled complex I and II
      as well as the supercomplex was significantly reduced in D620N fibroblasts.
      Importantly, inhibition of mitochondrial fission rescued the contents of
      assembled complexes as well as the functional defects in complex I and II.
      Overall, these results suggest that VPS35 D620N mutation-induced excessive
      mitochondrial fission leads to the defects in the assembled complex I and
      supercomplex and causes bioenergetics deficits.

PMID- 28765076
TI  - Utility and potential of rapid epidemic intelligence from internet-based sources.
AB  - OBJECTIVES: Rapid epidemic detection is an important objective of surveillance to
      enable timely intervention, but traditional validated surveillance data may not
      be available in the required timeframe for acute epidemic control. Increasing
      volumes of data on the Internet have prompted interest in methods that could use
      unstructured sources to enhance traditional disease surveillance and gain rapid
      epidemic intelligence. We aimed to summarise Internet-based methods that use
      freely-accessible, unstructured data for epidemic surveillance and explore their
      timeliness and accuracy outcomes. METHODS: Steps outlined in the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist were
      used to guide a systematic review of research related to the use of informal or
      unstructured data by Internet-based intelligence methods for surveillance.
      RESULTS: We identified 84 articles published between 2006-2016 relating to
      Internet-based public health surveillance methods. Studies used search queries,
      social media posts and approaches derived from existing Internet-based systems
      for early epidemic alerts and real-time monitoring. Most studies noted improved
      timeliness compared to official reporting, such as in the 2014 Ebola epidemic
      where epidemic alerts were generated first from ProMED-mail. Internet-based
      methods showed variable correlation strength with official datasets, with some
      methods showing reasonable accuracy. CONCLUSION: The proliferation of publicly
      available information on the Internet provided a new avenue for epidemic
      intelligence. Methodologies have been developed to collect Internet data and some
      systems are already used to enhance the timeliness of traditional surveillance
      systems. To improve the utility of Internet-based systems, the key attributes of
      timeliness and data accuracy should be included in future evaluations of
      surveillance systems.

PMID- 28765078
TI  - Evolution of the prevalence of hepatitis C virus infection and hepatitis C virus
      genotype distribution in human immunodeficiency virus-infected patients in Italy
      between 1997 and 2015.
AB  - OBJECTIVES: To analyse the variation of hepatitis C virus (HCV) prevalence and
      genotype distribution and their determinants in people living with human
      immunodeficiency virus (HIV) who entered care between 1997 and 2015. METHODS: HIV
      infected patients enrolled in ICONA who were tested for HCV antibodies (HCV-Ab)
      were included. RESULTS: Overall 3407 of 12 135 (28.1%) were HCV-Ab+; and 735 of
      12 135 (6.1%) were HBsAg+. Among patients whose HCV genotype was known, the most
      represented were genotypes 1 and 3. The prevalence of HCV infection decreased
      from 49.2% (2565/5217) during 1997-2002 to 10.2% (556/5466) during 2009-2015. The
      frequency of genotype 1a increased from 29.0% (264/911) to 43.0% (129/300),
      whereas genotype 3 decreased from 38.5% (351/911) to 27.0% (81/300). Independent
      predictors of HCV-Ab+ status were being female (adjusted OR (AOR) 1.23, 95% CI
      1.04-1.50, p = 0.01), risk category (versus injecting drug users: men who have
      sex with men AOR 0.01, 95% CI 0.01-0.01, p <0.001; heterosexuals AOR 0.01, 95% CI
      0.01-0.01, p <0.001; other/unknown AOR 0.02, 95% CI 0.01-0.02, p <0.001), being
      cared for in Central Italy (versus being cared for in Northern Italy: AOR 0.85,
      95% CI 0.73-0.98, p <0.001), being Italian-born (AOR 1.44, 95% CI 1.16-1.80, p =
      0.001) and being enrolled in less recent calendar years (versus 1997-2002: 2009
      2015 AOR 0.23, 95% CI 0.19-0.27, p <0.001; 2003-2008 AOR 0.49, 95% CI 0.41-0.61,
      p <0.001). CONCLUSIONS: The prevalence of HCV infection in HIV-infected patients
      entering into care in Italy significantly declined in more recent calendar years.
      After adjusting for risk factors and calendar years, HCV co-infection was more
      frequent in females and in those born in Italy.

PMID- 28765079
TI  - Developmental neurotoxicity and autism: A potential link between indoor
      neuroactive pollutants and the curious birth order risk factor.
AB  - Epidemiological and demographic studies find an increased risk of autism among
      first-borns. Toxicological studies show that some semi-volatile substances found
      in infant products produce adverse effects in neural and endocrine systems of
      animals, including behavioral and developmental effects. Several factors elevate
      the exposure of human infants to these chemicals. The highest exposures found in
      infants are comparable to the exposures that induce neural toxicity in animals. A
      review of these literatures suggests a linking hypothesis that could bridge the
      epidemiological and toxicological lines of evidence: an infant's exposure to
      neuroactive compounds emitted by infant products is increased by product newness
      and abundance; exposure is likely maximized for first-born children in families
      that can afford new products. Exposure is reduced for subsequently-born children
      who reuse these now neuroactive-depleted products. The presence of neuroactive
      chemical emissions from infant products has implications for birth-order effects
      and for other curious risk factors in autism, including gender, socioeconomic
      status, and season-of-birth risk factors.

PMID- 28765077
TI  - Resolution of vascular injury: Specialized lipid mediators and their evolving
      therapeutic implications.
AB  - Acute vascular injury occurs in a number of important clinical contexts,
      including spontaneous disease-related events (e.g. plaque rupture, thrombosis)
      and therapeutic interventions such as angioplasty, stenting, or bypass surgery.
      Endothelial cell (EC) disruption exposes the underlying matrix, leading to a
      rapid deposition of platelets, coagulation proteins, and leukocytes. A thrombo
      inflammatory response ensues characterized by leukocyte recruitment, vascular
      smooth muscle cell (VSMC) activation, and the elaboration of cytokines, reactive
      oxygen species and growth factors within the vessel wall. A resolution phase of
      vascular injury may be described in which leukocyte efflux, clearance of debris,
      and re-endothelialization occurs. VSMC migration and proliferation leads to the
      development of a thickened neointima that may lead to lumen compromise.
      Subsequent remodeling involves matrix protein deposition, and return of EC and
      VSMC to quiescence. Recent studies suggest that specialized pro-resolving lipid
      mediators (SPM) modulate key aspects of this response, and may constitute an
      endogenous homeostatic pathway in the vasculature. SPM exert direct effects on
      vascular cells that counteract inflammatory signals, reduce leukocyte adhesion,
      and inhibit VSMC migration and proliferation. These effects appear to be largely
      G-protein coupled receptor-dependent. Across a range of animal models of vascular
      injury, including balloon angioplasty, bypass grafting, and experimental aneurysm
      formation, SPM accelerate repair and reduce lesion formation. With bioactivity in
      the pM-nM range, a lack of discernible cytotoxicity, and a spectrum of vasculo
      protective properties, SPM represent a novel class of vascular therapeutics. This
      review summarizes current research in this field, including a consideration of
      critical next steps and challenges in translation.

PMID- 28765080
TI  - Activation of extrasynaptic delta-GABAA receptors globally or within the
      posterior-VTA has estrous-dependent effects on consumption of alcohol and estrous
      independent effects on locomotion.
AB  - Recent reports support higher than expected rates of binge alcohol consumption
      among women and girls. Unfortunately, few studies have assessed the mechanisms
      underlying this pattern of intake in females. Studies in males suggest that
      alcohol concentrations relevant to the beginning stages of binge intoxication may
      selectively target tonic GABAergic inhibition mediated by GABAA receptor subtypes
      expressing the delta-subunit protein (delta-GABAARs). Indeed, administration of
      agonists that interact with these delta-GABAARs prior to alcohol access can
      abolish binge drinking behavior in male mice. These delta-GABAARs have also been
      shown to exhibit estrous-dependent plasticity in regions relevant to drug taking
      behavior, like the hippocampus and periaqueductal gray. The present experiments
      were designed to determine whether the estrous cycle would alter binge drinking,
      or our ability to modulate this pattern of alcohol use with THIP, an agonist with
      high selectivity and efficacy at delta-GABAARs. Using the Drinking-in-the-Dark
      (DID) binge-drinking model, regularly cycling female mice were given 2h of daily
      access to alcohol (20%v/v). Vaginal cytology or vaginal impedance was assessed
      after drinking sessions to track estrous status. There was no fluctuation in
      binge drinking associated with the estrous cycle. Both Intra-posterior-VTA
      administration of THIP and systemic administration of the drug was also
      associated with an estrous cycle dependent reduction in drinking behavior. Pre
      treatment with finasteride to inhibit synthesis of 5alpha-reduced neurosteroids
      did not disrupt THIP's effects. Analysis of delta-subunit mRNA from posterior-VTA
      enriched tissue samples revealed that expression of this GABAA receptor subunit
      is elevated during diestrus in this region. Taken together, these studies
      demonstrate that deltaGABAARs in the VTA are an important target for binge
      drinking in females and confirm that the estrous cycle is an important moderator
      of the pharmacology of this GABAA receptor subtype.

PMID- 28765081
TI  - Intranasal oxytocin and a polymorphism in the oxytocin receptor gene are
      associated with human-directed social behavior in golden retriever dogs.
AB  - The oxytocin system may play an important role in dog domestication from the
      wolf. Dogs have evolved unique human analogue social skills enabling them to
      communicate and cooperate efficiently with people. Genomic differences in the
      region surrounding the oxytocin receptor (OXTR) gene have previously been
      associated with variation in dogs' communicative skills. Here we have utilized
      the unsolvable problem paradigm to investigate the effects of oxytocin and OXTR
      polymorphisms on human-directed contact seeking behavior in 60 golden retriever
      dogs. Human-oriented behavior was quantified employing a previously defined
      unsolvable problem paradigm. Behaviors were tested twice in a repeated,
      counterbalanced design, where dogs received a nasal dose of either oxytocin or
      saline 45min before each test occasion. Buccal DNA was analysed for genotype on
      three previously identified SNP-markers associated with OXTR. The same
      polymorphisms were also genotyped in 21 wolf blood samples to explore potential
      genomic differences between the species. Results showed that oxytocin treatment
      decreased physical contact seeking with the experimenter and one of the three
      polymorphisms was associated with degree of physical contact seeking with the
      owner. Dogs with the AA-genotype at this locus increased owner physical contact
      seeking in response to oxytocin while the opposite effect was found in GG
      genotype individuals. Hence, intranasal oxytocin treatment, an OXTR polymorphism
      and their interaction are associated with dogs' human-directed social skills,
      which can explain previously described breed differences in oxytocin response.
      Genotypic variation at the studied locus was also found in wolves indicating that
      it was present even at the start of dog domestication.

PMID- 28765083
TI  - Breast screening for survivors of breast cancer: A systematic review.
AB  - There is a large and growing population of women who have a personal history of
      breast cancer (PHBC). This systematic review was undertaken to explore the
      outcomes of surveillance mammography in breast cancer survivors, and to examine
      the evidence for screening these women within an organized population-based
      screening program. We searched Cochrane Central Register of Controlled Trials
      (CENTRAL Issue 6, 2015), OVID MEDLINE and EMBASE (January 2012 to June 22, 2015)
      for English-language studies of surveillance of the target population. A study
      author extracted study outcomes, which were audited by a research assistant. One
      systematic review and 5 primary studies were included. These showed that
      surveillance mammography may reduce breast cancer-specific mortality through
      early/asymptomatic detection (Hazard Ratio for those without compared to with
      symptoms:HR: 0.64, 95% CI 0.55 - 0.74). Three studies showed that semi-annual
      mammography is likely not of greater benefit than annual mammography. No evidence
      was found to suggest that surveillance mammography for women with a PHBC should
      not be conducted within an organized screening program. The small evidence-base
      had a high level of heterogeneity in populations, interventions and outcomes.
      Based on this review, organized screening programs should reassess their
      guidelines on surveillance mammography and consider including women with a PHBC.

PMID- 28765082
TI  - Is there a relationship between accelerometer-assessed physical activity and
      sedentary behavior and cognitive function in US Hispanic/Latino adults? The
      Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
AB  - Normative changes in cognitive function are expected with increasing age.
      Research on the relationship between normative cognitive decline and moderate-to
      vigorous physical activity (MVPA) and sedentary behavior (SED) needs further
      investigation in Hispanic/Latinos adults. We assessed the cross-sectional
      association between accelerometer assessed MVPA and SED with cognitive function
      in 7,478 adults aged 45-74years from the Hispanic Community Health Study/Study of
      Latinos. At baseline, cognitive tests included two executive function tests
      (Digit Symbol Substitution Test (DSST), a test of language (Word Fluency), and a
      test of memory (Spanish English Verbal Learning Test). Multiple regression models
      were used to examine associations of time spent in MVPA and SED with cognitive
      function by age groups, adjusted for age, education, sex, acculturation, and
      field center. Mean time spent in sedentary behaviors was 12.3h/day in females and
      11.9 h/day in males (75% and 77% of accelerometer wear time, respectively).
      Higher SED, but not MVPA, was associated with lower DSST raw scores (beta -0.03
      with each 10-min increment in SED; P<0.05), indicating lower performance in
      executive function in all age groups. No associations were observed for MVPA and
      SED with tests of language or memory tests. Our findings suggest a distinct
      association of SED but not MVPA on executive functioning in middle-aged and older
      Latino adults. Longitudinal studies are needed to more conclusively determine
      causal links.

PMID- 28765084
TI  - Surveillance of high-grade cervical cancer precursors (CIN III/AIS) in four
      population-based cancer registries, United States, 2009-2012.
AB  - Surveillance of cervical intraepithelial neoplasia grade III (CIN III) and
      adenocarcinoma in situ (AIS) is important for determining the burden of a
      preventable disease, identifying effects of vaccination on future diagnoses, and
      developing targeted programs. We analyzed population-based rates of high-grade
      cervical cancer precursor lesions using data from four central cancer registries
      (diagnosis years 2009-2012 from Louisiana, Kentucky, Michigan, and diagnosis
      years 2011-2012 from Los Angeles) by age, race, and histology. We also compared
      rates of precursors to invasive cancers. With 4 complete years of data from
      Michigan, we were able to conduct a trend analysis for that state. Data analysis
      was conducted in Atlanta during 2016. Kentucky reported the highest rate of CIN
      III/AIS (69.8), followed by Michigan (55.4), Louisiana (42.3), and Los Angeles
      (19.2). CIN III/AIS rates declined among women in Michigan by 37% each year for
      women aged 15-19, 14% for those aged 20-24, and 7% for those aged 25-29. Rates of
      CIN III/AIS vary by registry, and were higher than invasive cancer. In Michigan,
      declines in CIN III/AIS among women aged 15-29 are likely related in part to
      updated screening recommendations, and to the impact of human papillomavirus
      vaccination.

PMID- 28765085
TI  - A preregistered, direct replication attempt of the retrieval-extinction effect in
      cued fear conditioning in rats.
AB  - In 2009, Monfils and colleagues proposed a behavioral procedure that was said to
      result in a permanent attenuation of a previously established fear memory,
      thereby precluding a possible return of fear after extinction (Monfils,
      Cowansage, Klann, & LeDoux, 2009). By presenting a single retrieval trial one
      hour before standard extinction training, they found an enduring reduction of
      fear. The retrieval-extinction procedure holds great clinical potential,
      particularly for anxiety patients, but the findings are not undisputed, and
      several conceptual replications have failed to reproduce the effect. These
      failures have largely been attributed to small procedural differences. This
      preregistered study is the first endeavor to exactly replicate three key
      experiments of the original report by Monfils et al. (2009), thereby gauging the
      robustness of their seminal findings. Despite adhering to the original procedures
      as closely as possible, we did not find any evidence for reduced return of fear
      with the retrieval-extinction procedure relative to regular extinction training,
      as assessed through spontaneous recovery, reinstatement and renewal. Behavior of
      animals in the control condition (extinction only) was comparable to that in the
      original studies and provided an adequate baseline to reveal differences with the
      retrieval-extinction condition. Our null findings indicate that the effect sizes
      in the original paper may have been inflated and question the legitimacy of
      previously proposed moderators of the retrieval-extinction effect. We argue that
      direct experimental evaluation of purported moderators of the retrieval
      extinction effect will be key to shed more light on its nature and prerequisites.

PMID- 28765086
TI  - Spectrum of atrial arrhythmias using the ligament of Marshall in patients with
      atrial fibrillation.
AB  - BACKGROUND: The role of the ligament of Marshall (LOM) in patients with atrial
      fibrillation (AF) has not been well defined. OBJECTIVE: The purpose of this study
      was to describe the role of the LOM in patients with AF and related arrhythmias.
      METHODS: Fifty-six patients (mean age 63 +/- 11 years; persistent AF in 48 [86%];
      ejection fraction 0.49 +/- 0.13; left atrial diameter 4.7 +/- 0.6 cm) with LOM
      mediated arrhythmias were included. RESULTS: A LOM-pulmonary vein (PV) connection
      was present in 18 patients (32%) and was eliminated with radiofrequency (RF)
      ablation at the left lateral ridge or crux (n = 12), at the mitral annulus (n =
      3), or with alcohol/ethanol (EtOH) ablation of the vein of Marshall (VOM; n = 3).
      A LOM-mediated atrial tachycardia (AT) was present in 13 patients (23%). Thirty
      one patients with refractory mitral isthmus conduction were referred for
      potential EtOH ablation. In the 6 patients in whom VOM was injected during
      perimitral reentry, EtOH resulted in slowing in 3 patients and termination in 1
      patient. In others, EtOH infusion resulted in complete isolation of the left
      sided PVs and left atrial appendage. Repeat RF and adjunctive EtOH ablation of
      the VOM tended to be more effective in creating conduction block across the
      mitral isthmus than RF ablation alone (P = .057). CONCLUSION: The LOM is
      responsible for a variety of arrhythmia mechanisms in patients with AF and atrial
      tachycardia. It may be ablated at any point along its course, at the mitral
      annulus, at the lateral ridge/PV antrum, and epicardially in the coronary sinus
      and the VOM itself. EtOH ablation of the VOM may be an adjunctive strategy in
      patients with refractory perimitral reentry.

PMID- 28765087
TI  - Circadian variability patterns predict and guide premature ventricular
      contraction ablation procedural inducibility and outcomes.
AB  - BACKGROUND: Infrequent intraprocedural premature ventricular complexes (PVCs) may
      impede radiofrequency catheter ablation (RFA) outcome, and pharmacologic
      induction is unpredictable. OBJECTIVE: The purpose of this study was to determine
      whether PVC circadian variation could help predict drug response. METHODS:
      Consecutive patients referred for RFA with detailed Holter monitoring and
      frequent monomorphic PVCs were included. Patients were divided into 3 groups
      based on hourly PVC count relationship to corresponding mean heart rate (HR)
      during each of the 24 hours on Holter: fast-HR-dependent PVC (F-HR-PVC) type for
      a positive correlation (Pearson, P <.05), slow-HR-dependent PVC (S-HR-PVC) type
      for a negative correlation, and independent-HR-PVC (I-HR-PVC) when no correlation
      was found. RESULTS: Fifty-one of the 101 patients (50.5%) had F-HR-PVC, 39.6% I
      HR-PVC, and 9.9% S-HR-PVC; 30.7% had infrequent intraprocedural PVC requiring
      drug infusion. The best predictor of infrequent PVC was number of hours with PVC
      count <120/h on Holter (area under the curve 0.80, sensitivity 83.9%, specificity
      74.3%, for >=2 h). Only F-HR-PVC patients responded to isoproterenol.
      Isoproterenol washout or phenylephrine infusion was successful for the 3 S-HR-PVC
      patients, and no drug could increase PVC frequency in the 12 I-HR-PVC patients.
      Long-term RFA success rate in patients with frequent PVCs at baseline (82.9%) was
      similar to those with infrequent PVC who responded to a drug (77.8%; P = .732)
      but significantly higher than for those who did not respond to any drug (15.4%; P
      <.0001). CONCLUSION: A simple analysis of Holter PVC circadian variability
      provides incremental value to guide pharmacologic induction of PVCs during RFA
      and predict outcome. Patients with infrequent I-HR-PVC had the least successful
      outcomes from RF ablation.

PMID- 28765089
TI  - Crossing the slow pathway bridge: A better method for decreasing long-term
      recurrences after cryoablation of atrioventricular nodal reentrant tachycardia?

PMID- 28765088
TI  - The evolving role of ankyrin-B in cardiovascular disease.
AB  - Over the past decade, ankyrin-B has been identified as a prominent player in
      cardiac physiology. Ankyrin-B has a multitude of functions, with roles in
      expression, localization, and regulation of proteins critical for cardiac
      excitability, cytoskeletal integrity, and signaling. Furthermore, human ANK2
      variants that result in ankyrin-B loss of function are associated with "ankyrin-B
      syndrome," a complex cardiac phenotype that may include bradycardia and heart
      rate variability, conduction block, atrial fibrillation, QT interval
      prolongation, and potentially fatal catecholaminergic polymorphic ventricular
      tachycardia. However, our understanding of the molecular mechanisms underlying
      ankyrin-B function at baseline and in disease is still not fully developed owing
      to the complexity of ankyrin-B gene regulation, number of ankyrin-B-associated
      molecules, multiple roles of ankyrin-B in the heart and other organs that
      modulate cardiac function, and a host of unexpected clinical phenotypes. In this
      review, we summarize known roles of ankyrin-B in the heart and the impact of
      ankyrin-B dysfunction in animal models and in human disease as well as highlight
      important new findings illustrating the complexity of ankyrin-B signaling.

PMID- 28765090
TI  - Data relating to prenatal lead exposure and child IQ at 4 and 8 years old in the
      Avon Longitudinal Study of Parents and Children.
AB  - As part of the Avon Longitudinal Study of Parents and Children (ALSPAC), measures
      of child IQ were collected by trained psychologists. The Wechsler Pre-school and
      Primary Scale of Intelligence - Revised UK edition (WPPSI) was used at age 4
      years in a subsample of children enrolled in ALSPAC (the Children in Focus
      cohort), chosen at random from the last 6 months of ALSPAC births (about 10% of
      the participants). At age 8 years all children enrolled in the main cohort were
      invited to complete a short form of the Wechsler Intelligence Scale for Children
      (WISC)-III UK. Prenatal blood lead (B-Pb) concentrations were measured by
      inductively-couple plasma mass spectrometry in samples from women at a median
      gestation age of 11 weeks. Child blood lead was measured by atomic absorption
      spectrometry in samples from children attending the Children in Focus clinic at
      age 30 months. Maternal reports at 32 weeks' gestation were used to generate data
      on a range of potential confounders. The data were used to determine the
      associations between prenatal exposure to lead and child IQ at 4 and 8 years. The
      effect of child B-Pb at 3 years as a moderator of these associations was tested.
      (For results, please see doi:10.1016/j.neuro.2017.07.003 Taylor et al., (2017)).

PMID- 28765091
TI  - Lead exposure and tau hyperphosphorylation: An in vitro study.
AB  - The presence of fibrillary lesions, which are mainly composed of the microtubule
      associated protein tau (MAPT) in neurons, has gained immense recognition due to
      their presence in numerous neurodegenerative diseases, including Alzheimer's
      disease (AD). Dysregulation of tau is related with its altered site-specific
      phosphorylation which is followed by tau polymerization, neuronal dysfunction and
      death. Previous reports by us suggest that molecular alterations favor abundant
      tau phosphorylation and immunoreactivity in the frontal cortex of aged primates
      and rodents with past exposure to lead (Pb). Here we report the involvement of Pb
      induced alterations in tau and hyperphosphorylation of tau in differentiated
      Human Neuroblastoma SH-SY5Y cells exposed to a series of Pb concentrations (5
      100MUM) for 48h. These cells were analyzed for the protein expression of total
      tau, site-specific tau hyperphosphorylation, cyclin dependent kinase 5 (CDK5) and
      p35/p25 at selected time points (24-144h), after Pb exposure had ceased. Western
      blot analysis revealed aberrant tau levels as well as site-specific tau
      hyperphosphorylation accompanied by elevated CDK5 levels and altered protein
      ratio of p35/p25 particularly at 72 and 144h. These changes provide additional
      evidence that neurodegenerative events are subject to environmental influences.

PMID- 28765092
TI  - Phylogenetic evaluation of Amynthas earthworms from South China reveals the
      initial ancestral state of spermathecae.
AB  - Our knowledge of the phylogeny of the earthworm genus Amynthas under the family
      Megascolecidae, which is comprised of a huge number of species, is very limited
      compared to the better-known and much smaller family Lumbricidae. In order to
      investigate the phylogenetic relationships among the species within the genus
      Amynthas, which is the largest genus of the Megascolecidae family, nuclear and
      mitochondrial DNA sequences of 77 species, including 76 in-group Amynthas species
      collected from South China and 1 out-group species, were analyzed. A 5402bp
      segments composed of whole nuclear 18S rDNA and the mitochondrial genes COI,
      COII, ND1, 12S, and 16S was assembled from 77 species. Maximum Likelihood and
      Bayesian analyses of the concatenated sequences were performed. The results
      revealed evolution of two geographically independent lineages, both showing the
      ancestral state of two pairs of spermatheca (Sp.p 7/8/9). We found the species
      groups described by Sims and Easton (1972) to be non-monophyletic, and the origin
      of the parthenogenetic species group to likely be a quadthecal ancestor. These
      results provide modest evidence in support of an Indochinese peninsula origin of
      the Chinese Amynthas species and divergence of the genus once it had spread to
      mainland China. The findings of this study are consistent with a divergence
      scenario that resulted in at least one branch spreading to the Southeast of China
      and another branch spreading to the Southwest of China, but further research is
      required to confirm this interpretation of the Amynthas phylogeny.

PMID- 28765093
TI  - Mitochondrial protein transport in health and disease.
AB  - Mitochondria are fundamental structures that fulfil important and diverse
      functions within cells, including cellular respiration and iron-sulfur cluster
      biogenesis. Mitochondrial function is reliant on the organelles proteome, which
      is maintained and adjusted depending on cellular requirements. The majority of
      mitochondrial proteins are encoded by nuclear genes and must be trafficked to,
      and imported into the organelle following synthesis in the cytosol. These nuclear
      encoded mitochondrial precursors utilise dynamic and multimeric translocation
      machines to traverse the organelles membranes and be partitioned to the
      appropriate mitochondrial subcompartment. Yeast model systems have been
      instrumental in establishing the molecular basis of mitochondrial protein import
      machines and mechanisms, however unique players and mechanisms are apparent in
      higher eukaryotes. Here, we review our current knowledge on mitochondrial protein
      import in human cells and how dysfunction in these pathways can lead to disease.

PMID- 28765094
TI  - Non-coding RNAs as a new dawn in tumor diagnosis.
AB  - The current knowledge about non-coding RNAs (ncRNAs) as important regulators of
      gene expression in both physiological and pathological conditions, has been the
      main engine for the design of innovative platforms to finalize the
      pharmacological application of ncRNAs as either therapeutic tools or as molecular
      biomarkers in cancer. Biochemical alterations of cancer cells are, in fact,
      largely supported by ncRNA disregulation in the tumor site, which, in turn,
      reflects the cancer-associated specific modification of circulating ncRNA
      expression pattern. The aim of this review is to describe the state of the art of
      pre-clinical and clinical studies that analyze the involvement of miRNAs and
      lncRNAs in cancer-related processes, such as proliferation, invasion and
      metastases, giving emphasis to their functional role. A central node of our work
      has been also the examination of advantages and criticisms correlated with the
      clinical use of ncRNAs, taking into account the pressing need to refine the
      profiling methods aimed at identify novel diagnostic and prognostic markers and
      the request to optimize the delivery of such nucleic acids for a therapeutic use
      in an imminent future.

PMID- 28765095
TI  - Suggestion of the updated IVIS cut-off values for identifying non-ocular
      irritants in the bovine corneal opacity and permeability (BCOP) assay.
AB  - The bovine corneal opacity and permeability (BCOP) assay is an alternative to the
      Draize test in rabbits. Although it can be used to evaluate ocular non-irritants
      and severe irritants, it is not used for the assessment of mild-irritating
      substances. In this assay, a chemical with an in vitro irritancy score (IVIS)<=3
      is defined as a "non-irritant" while one with an IVIS>55 is defined as a
      "corrosive" or "severe irritant." We attempted to evaluate mild eye irritants by
      assessing the recovery of corneal lesions histopathologically. Our results
      indicated that chemicals with IVIS<=6 may be defined as "non-irritants," because
      the rapid recovery of lesions limited to the squamous layer was predicted by the
      histopathology. In cases where lesions extended to the wing and basal cell
      layers, when some intact basal cells remained, the lesions were also predicted to
      be reversible. Thus, chemicals which induce lesions in which basal cells remain
      intact can be considered to be mild irritants.

PMID- 28765096
TI  - Effects of BPA on global DNA methylation and global histone 3 lysine
      modifications in SH-SY5Y cells: An epigenetic mechanism linking the regulation of
      chromatin modifiying genes.
AB  - Bisphenol A (BPA), an estrogenic endocrine disruptor, is widely used in the
      production of polycarbonate plastic and epoxy resins, resulting in high risk on
      human health. In present study we aimed to investigate the effects of BPA on
      global and gene specific DNA methylation, global histone modifications and
      regulation of chromatin modifiying enzymes in human neuroblastoma cells (SH
      SY5Y). Cells were treated with BPA at 0.1, 1 and 10MUM concentrations for 48 and
      96h. IC50 value of BPA was determined as 183 and 129MUM in SH-SY5Y cells after
      24h by MTT and NRU tests, respectively. We observed significant alterations on
      the 5-mC% levels (1.3 fold) and 5-hmC% levels (1.67 fold) after 10MUM of BPA for
      96h. Significant decrease was identified in H3K9me3 and H3K9ac after 10MUM of BPA
      for 96h while decrease was observed in H3K4me3 at 10MUM of BPA for 48h.
      Alterations were observed in chromatin modifiying genes including G9a, EZH2,
      SETD8, SETD1A, HAT1, SIRT1, DNMT1, RIZ1 and Suv39h1 after 96h of BPA exposure.
      Taken together, this study suggests that BPA might modulate the epigenetic
      regulators which would be key molecular events in the toxicity of endocrine
      disrupting chemicals.

PMID- 28765097
TI  - Selenium triggers Nrf2-mediated protection against cadmium-induced chicken
      hepatocyte autophagy and apoptosis.
AB  - Cadmium (Cd) is a ubiquitously distributed trace metal and environmental
      pollutant that is highly toxic to liver. Selenium (Se) may provide
      chemoprotection against Cd-induced cytotoxicity by augmenting the cellular
      antioxidant capacity. However, the mechanism of Se chemoprotection against Cd
      induced hepatotoxicity is unclear. The present study evaluated the ameliorative
      properties of Se against Cd-induced cytotoxicity in hepatocytes. Primary cells
      were exposed to 5MUM Cd and/or 1MUM Se for 24h. Cellular morphology and function,
      antioxidant status, activation of Nrf2 pathway, autophagy and apoptosis were
      determined. These results indicated that Se ameliorated the cytotoxicity of Cd by
      recovering hepatocyte morphology and function, inhibiting reactive oxygen species
      (ROS) and malondialdehyde (MDA) production, reducing intracellular LDH release,
      autophagy and apoptosis, and increasing the major antioxidative activities (Total
      antioxidant capacity (T-AOC) and superoxide dismutase (SOD). In summary, Cd is a
      hepatotoxin that causes hepatocytes damage by inducing oxidative stress,
      excessive autophagy and apoptosis as a mechanism of toxicity. Moreover, Se
      supplement ameliorated these effects by enhancing antioxidant systems, decreasing
      excessive autophagy and apoptosis. These results suggested that Se triggers Nrf2
      mediated protection as the mechanism of Se chemoprotection against Cd-induced
      autophagy and apoptosis.

PMID- 28765098
TI  - Vertebral body bone mineral density in patients with lumbar spondylolysis: a
      quantitative CT study.
AB  - PURPOSE: Spondylolysis is known to be a part of a disease process, which
      describes a defect in the pars interarticularis of vertebra. We aimed to use
      quantitative computed tomography (QCT) to measure vertebral body bone mineral
      density (BMD) in patients with lumbar spondylolysis and compare it with readings
      in controls. METHODS: Forty symptomatic patients with lumbar spondylolysis aged
      18-52 years and 40 matched controls of same sex and approximate age (+/-2 years)
      were included in the study. Measurements of BMD were performed by QCT analysis
      for each vertebral body from T12 to L5 and mean BMD was calculated for each case.
      RESULTS: Of 40 patients, 22 (55%) demonstrated L5 spondylolysis, 14 (35%) L4
      spondylolysis, three (7.5%) L3 spondylolysis, and one (2.5%) L2 spondylolysis.
      Spondylolisthesis was found in 29 patients (73%). Patients with spondylolisthesis
      were significantly older than patients without spondylolisthesis (42+/-6.9 vs.
      37.2+/-5.4, P = 0.024). Mean BMD value of the patient group was significantly
      lower than that of the controls (105+/-24 mg/cm3 vs. 118.7+/-25.6 mg/cm3, P =
      0.015). Subgroup analysis of 19 patients and 19 controls under the age of 40
      revealed that the mean BMD value of the patients was significantly lower than
      that of the controls in the younger age group as well (108.7+/-23.5 mg/cm3 vs.
      130+/-25.8 mg/cm3, P = 0.009). CONCLUSION: This study demonstrated that patients
      with spondylolysis had significantly lower mean vertebral body BMD compared with
      controls.

PMID- 28765099
TI  - Individual Prognosis of Symptom Burden and Functioning in Chronic Diseases: A
      Generic Method Based on Patient-Reported Outcome (PRO) Measures.
AB  - BACKGROUND: Information to the patient about the long-term prognosis of symptom
      burden and functioning is an integrated part of clinical practice, but relies
      mostly on the clinician's personal experience. Relevant prognostic models based
      on patient-reported outcome (PRO) data with repeated measurements are rarely
      available. OBJECTIVE: The aim was to describe a generic method for individual
      long-term prognosis of symptom burden and functioning that implied few
      statistical presumptions, to evaluate an implementation for prognosis of
      depressive symptoms in stroke patients and to provide open access to a Web-based
      prototype of this implementation for individual use. METHODS: The method used to
      describe individual prognosis of a PRO outcome was based on the selection of a
      specific subcohort of patients who have the same score as the patient in question
      at the same time (eg, after diagnosis or treatment start), plus or minus one unit
      of minimal clinically important difference. This subcohort's experienced courses
      were then used to provide quantitative measures of prognosis over time. A cohort
      of 1404 stroke patients provided data for a simulation study and a prototype for
      individual use. Members of the cohort answered questionnaires every 6 months for
      3.5 years. Depressive symptoms were assessed by the Hospital Anxiety and
      Depression Scale (HADS) and a single item from the SF-12 (MH4) health survey.
      Four approaches were compared in a simulation study in which the prognosis for
      each member of the cohort was individually assessed. RESULTS: The mean standard
      deviations were 40% to 70% higher in simulated scores. Mean errors were close to
      zero, and mean absolute errors were between 0.46 and 0.66 SD in the four
      approaches. An approach in which missing HADS scores were estimated from the
      single-item SF-12 MH4 performed marginally better than methods restricted to
      questionnaires with a genuine HADS score, which indicates that data collected
      with shorter questionnaires (eg, in clinical practice) may be used together with
      longer versions with the full scale, given that the design includes at least two
      simultaneous measurements of the full scale and the surrogate measure.
      CONCLUSIONS: This is the first description and implementation of a nonparametric
      method for individual PRO-based prognosis. Given that relevant PRO data have been
      collected longitudinally, the method may be applied to other patient groups and
      to any outcome related to symptom burden and functioning. This initial
      implementation has been deliberately made simple, and further elaborations as
      well as the usability and clinical validity of the method will be scrutinized in
      clinical practice. An implementation of the prototype is available online at
      www.prognosis.dk.

PMID- 28765100
TI  - Pacing, Conventional Physical Activity and Active Video Games to Increase
      Physical Activity for Adults with Myalgic Encephalomyelitis/Chronic Fatigue
      Syndrome: Protocol for a Pilot Randomized Controlled Trial.
AB  - BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a
      serious illness of biological origin characterized by profound physical and
      cognitive exhaustion and postexertion malaise. Pacing is a common strategy used
      to manage available energy and complete activities of daily living; yet little
      research has investigated this as a strategy to increase physical activity
      levels. Typically, people living with ME/CFS are faced by unique barriers to
      physical activity participation and are less physically active than healthy
      peers. As such they are at increased risk of physical inactivity-related health
      consequences. Active video games may be a feasible and acceptable avenue to
      deliver physical activity intervention by overcoming many of the reported
      barriers to participation. OBJECTIVE: The primary objective of this pilot study
      is to determine the feasibility and acceptability of active video games to
      increase physical activity levels of people with ME/CFS. The secondary aims are
      to explore the preliminary effectiveness of pacing and active video gaming to
      pacing alone and pacing plus conventional physical activity to increase the
      physical activity levels of adults with ME/CFS and explore the relationship
      between physical activity and cumulative inflammatory load (allostatic load).
      METHODS: This study will use a mixed method design, with a 3-arm pilot randomized
      controlled trial, exit interviews, and collection of feasibility and process
      data. A total of 30 adults with ME/CFS will be randomized to receive either (1)
      pacing, (2) pacing and conventional physical activity, or (3) pacing and active
      video gaming. The intervention duration will be 6 months, and participants will
      be followed up for 6 months postintervention completion. The intervention will be
      conducted in the participant's home, and activity intensity will be determined by
      continuously monitored heart rate and ratings of perceived exertion. Feasibility
      and acceptability and process data will be collected during and at the end of the
      intervention. Health-related outcomes (eg, physical activity, blood samples,
      quality of life, and functioning) will be collected at baseline, end of
      intervention, and 6 months after intervention completion. RESULTS: This protocol
      was developed after 6 months of extensive stakeholder and community consultation.
      Enrollment began in January 2017; as of publication, 12 participants were
      enrolled. Baseline testing is scheduled to commence in mid-2017. CONCLUSIONS:
      This pilot study will provide essential feasibility and acceptability data which
      will guide the use of active video games for people with ME/CFS to increase their
      physical activity levels. Physical activity promotion in this clinical population
      has been poorly and under-researched, and any exploration of alternative physical
      activity options for this population is much needed. TRIAL REGISTRATION:
      Australia New Zealand Clinical Trials Registry: ACTRN12616000285459;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370224 (Archived
      by WebCite at http://www.webcitation.org/6qgOLhWWf).

PMID- 28765101
TI  - Systematic Review Protocol to Assess the Effectiveness of Usability
      Questionnaires in mHealth App Studies.
AB  - BACKGROUND: Usability questionnaires have a wide use in mobile health (mHealth)
      app usability studies. However, no systematic review has been conducted for
      assessing the effectiveness of these questionnaires. OBJECTIVE: This paper
      describes a protocol for conducting a systematic review of published
      questionnaire-based mHealth app usability studies. METHODS: In this systematic
      review, we will select recently published (2008-2017) articles from peer-reviewed
      journals and conferences that describe mHealth app usability studies and
      implement at least one usability questionnaire. The search strategy will include
      terms such as "mobile app" and "usability." Multiple databases such as PubMed,
      CINAHL, IEEE Xplore, ACM Digital Library, and INSPEC will be searched. There will
      be 2 independent reviewers in charge of screening titles and abstracts as well as
      determining those articles that should be included for a full-text review. The
      third reviewer will act as a mediator between the other 2 reviewers. Moreover, a
      data extraction form will be created and used during the full article data
      analysis. Notably, the Preferred Reporting Items for Systematic Review and Meta
      Analysis Protocols (PRISMA-P) guidelines will be followed in reporting this
      protocol. RESULTS: A preliminary search produced 1271 articles, 40 of which are
      duplicate records. The inclusion-exclusion criteria are being strictly followed
      in performing the ongoing study selection. CONCLUSIONS: Usability questionnaires
      are an important tool in mHealth app usability studies. This review will
      summarize the usability questionnaires used in published research articles while
      assessing the efficacy of these questionnaires in determining the usability of
      mHealth apps.

PMID- 28765102
TI  - Beliefs, Knowledge, Implementation, and Integration of Evidence-Based Practice
      Among Primary Health Care Providers: Protocol for a Scoping Review.
AB  - BACKGROUND: The adoption of evidence-based practice (EBP) is promoted because it
      is widely recognized for improving the quality and safety of health care for
      patients, and reducing avoidable costs. Providers of primary care face numerous
      challenges to ensuring the effectiveness of their daily practices. Primary health
      care is defined as: the entry level into a health care services system, providing
      a first point of contact for all new needs and problems; patient-focused (not
      disease-oriented) care over time; care for all but the most uncommon or unusual
      conditions; and coordination or integration of care, regardless of where or by
      whom that care is delivered. Primary health care is the principal means by which
      to approach the main goal of any health care services system: optimization of
      health status. OBJECTIVE: This review aims to scope publications examining
      beliefs, knowledge, implementation, and integration of EBPs among primary health
      care providers (HCPs). METHODS: We will conduct a systematic scoping review of
      published articles in the following electronic databases, from their start dates
      until March 31, 2017: Medical Literature Analysis and Retrieval System Online
      (MEDLINE) via PubMed (from 1946), Embase (from 1947), Cumulative Index to Nursing
      and Allied Health Literature (CINAHL; from 1937), the Cochrane Central Register
      of Controlled Trials (CENTRAL; from 1992), PsycINFO (from 1806), Web of Science
      (from 1900), Joanna Briggs Institute (JBI) database (from 1998), Database of
      Abstracts of Reviews of Effects (DARE; from 1996), Trip medical database (from
      1997), and relevant professional scientific journals (from their start dates). We
      will use the predefined search terms of, "evidence-based practice" and, "primary
      health care" combined with other terms, such as, "beliefs", "knowledge",
      "implementation", and "integration". We will also conduct a hand search of the
      bibliographies of all relevant articles and a search for unpublished studies
      using Google Scholar, ProQuest, Mednar, and WorldCat. We will consider
      publications in English, French, Spanish, and Portuguese. RESULTS: The electronic
      database searches were completed in April 2017. Retrieved articles are currently
      being screened, and the entire study is expected to be completed by November
      2017. CONCLUSIONS: This systematic scoping review will provide a greater
      understanding of the beliefs, knowledge, implementation, and integration of EBPs
      among primary HCPs. The findings will inform clinical practice and help to draw a
      global picture of the EBP research topics that are relevant to primary care
      providers.

PMID- 28765104
TI  - A Technological Innovation to Reduce Prescribing Errors Based on Implementation
      Intentions: The Acceptability and Feasibility of MyPrescribe.
AB  - BACKGROUND: Although prescribing of medication in hospitals is rarely an error
      free process, prescribers receive little feedback on their mistakes and ways to
      change future practices. Audit and feedback interventions may be an effective
      approach to modifying the clinical practice of health professionals, but these
      may pose logistical challenges when used in hospitals. Moreover, such
      interventions are often labor intensive. Consequently, there is a need to develop
      effective and innovative interventions to overcome these challenges and to
      improve the delivery of feedback on prescribing. Implementation intentions, which
      have been shown to be effective in changing behavior, link critical situations
      with an appropriate response; however, these have rarely been used in the context
      of improving prescribing practices. OBJECTIVE: Semistructured qualitative
      interviews were conducted to evaluate the acceptability and feasibility of
      providing feedback on prescribing errors via MyPrescribe, a mobile-compatible
      website informed by implementation intentions. METHODS: Data relating to 200
      prescribing errors made by 52 junior doctors were collected by 11 hospital
      pharmacists. These errors were populated into MyPrescribe, where prescribers were
      able to construct their own personalized action plans. Qualitative interviews
      with a subsample of 15 junior doctors were used to explore issues regarding
      feasibility and acceptability of MyPrescribe and their experiences of using
      implementation intentions to construct prescribing action plans. Framework
      analysis was used to identify prominent themes, with findings mapped to the
      behavioral components of the COM-B model (capability, opportunity, motivation,
      and behavior) to inform the development of future interventions. RESULTS:
      MyPrescribe was perceived to be effective in providing opportunities for critical
      reflection on prescribing errors and to complement existing training (such as
      junior doctors' e-portfolio). The participants were able to provide examples of
      how they would use "If-Then" plans for patient management. Technology, as opposed
      to other methods of learning (eg, traditional "paper based" learning), was seen
      as a positive advancement for continued learning. CONCLUSIONS: MyPrescribe was
      perceived as an acceptable and feasible learning tool for changing prescribing
      practices, with participants suggesting that it would make an important addition
      to medical prescribers' training in reflective practice. MyPrescribe is a novel
      theory-based technological innovation that provides the platform for doctors to
      create personalized implementation intentions. Applying the COM-B model allows
      for a more detailed understanding of the perceived mechanisms behind prescribing
      practices and the ways in which interventions aimed at changing professional
      practice can be implemented.

PMID- 28765103
TI  - Key Components in eHealth Interventions Combining Self-Tracking and Persuasive
      eCoaching to Promote a Healthier Lifestyle: A Scoping Review.
AB  - BACKGROUND: The combination of self-tracking and persuasive eCoaching in
      automated interventions is a new and promising approach for healthy lifestyle
      management. OBJECTIVE: The aim of this study was to identify key components of
      self-tracking and persuasive eCoaching in automated healthy lifestyle
      interventions that contribute to their effectiveness on health outcomes,
      usability, and adherence. A secondary aim was to identify the way in which these
      key components should be designed to contribute to improved health outcomes,
      usability, and adherence. METHODS: The scoping review methodology proposed by
      Arskey and O'Malley was applied. Scopus, EMBASE, PsycINFO, and PubMed were
      searched for publications dated from January 1, 2013 to January 31, 2016 that
      included (1) self-tracking, (2) persuasive eCoaching, and (3) healthy lifestyle
      intervention. RESULTS: The search resulted in 32 publications, 17 of which
      provided results regarding the effect on health outcomes, 27 of which provided
      results regarding usability, and 13 of which provided results regarding
      adherence. Among the 32 publications, 27 described an intervention. The most
      commonly applied persuasive eCoaching components in the described interventions
      were personalization (n=24), suggestion (n=19), goal-setting (n=17), simulation
      (n=17), and reminders (n=15). As for self-tracking components, most interventions
      utilized an accelerometer to measure steps (n=11). Furthermore, the medium
      through which the user could access the intervention was usually a mobile phone
      (n=10). The following key components and their specific design seem to influence
      both health outcomes and usability in a positive way: reduction by setting short
      term goals to eventually reach long-term goals, personalization of goals, praise
      messages, reminders to input self-tracking data into the technology, use of
      validity-tested devices, integration of self-tracking and persuasive eCoaching,
      and provision of face-to-face instructions during implementation. In addition,
      health outcomes or usability were not negatively affected when more effort was
      requested from participants to input data into the technology. The data extracted
      from the included publications provided limited ability to identify key
      components for adherence. However, one key component was identified for both
      usability and adherence, namely the provision of personalized content.
      CONCLUSIONS: This scoping review provides a first overview of the key components
      in automated healthy lifestyle interventions combining self-tracking and
      persuasive eCoaching that can be utilized during the development of such
      interventions. Future studies should focus on the identification of key
      components for effects on adherence, as adherence is a prerequisite for an
      intervention to be effective.

PMID- 28765105
TI  - Global drive to increase breast feeding is unveiled.

PMID- 28765106
TI  - The level of provision of specialist palliative care services in Scotland: an
      international benchmarking study.
AB  - OBJECTIVES: Comparative benchmarking of specialist palliative care (SPC) services
      across jurisdictions can be used to assess the adequacy of provision. Published
      in 2016, the Scottish Atlas of Palliative Care unlocks the possibility of
      benchmarking Scotland's provision against other European Union (EU) countries.
      Our objectives were to describe the provision of SPC services in Scotland and
      compare this with other EU countries, assessing coverage against European norms.
      METHODS: We conducted a secondary analysis of data collected as part for the
      Scottish Atlas by structured telephone (n=33) or online (n=3) survey with
      informants from 14 territorial health boards and 15 hospices who provided
      information about SPC services in their locality. National-level Scottish data
      were compared with data from other EU countries allowing ranking for each service
      type and service coverage as calculated against European Association for
      Palliative Care norms. RESULTS: Scotland had a total of 23 SPC inpatient units
      containing 349 beds, 27 SPC hospital support teams and 38 SPC home care teams.
      Relative to other EU countries, Scotland ranked seventh for provision of SPC
      inpatient units and hospital support teams, and fifth for home care teams.
      Coverage for these services was 85%, 100% and 72%, respectively. CONCLUSION:
      Scotland is positioned among the top 10 EU countries for the level of provision
      of SPC services. National policy in Scotland has focused on the delivery of
      palliative care at home or in a homely setting. These data support a focus on
      developing services in community settings to meet Scotland's policy ambitions.

PMID- 28765107
TI  - David Oliver: Is the NHS trying to help or bully social care?

PMID- 28765108
TI  - How a fight for Charlie Gard became a fight against the state.

PMID- 28765109
TI  - NHS England's plan to reduce wasteful and ineffective drug prescriptions.

PMID- 28765110
TI  - Fireflies in The BMJ's wrapping.

PMID- 28765114
TI  - The GENIE Is Out of the Bottle: Landmark Cancer Genomics Dataset Released.
AB  - <b/> In this issue of Cancer Discovery, an overview of the AACR Project GENIE, a
      landmark study in cancer genomics, is presented by The AACR Project GENIE
      Consortium. A summary of the goals and objectives of this ambitious program is
      provided, together with an analysis of the phase I cohort of 19,000 samples.
      Cancer Discov; 7(8); 796-8. (c)2017 AACR.See related article by The AACR Project
      GENIE Consortium, p. 818.

PMID- 28765115
TI  - Refining Targeted Therapy Opportunities for BRAF-Mutant Melanoma.
AB  - <b/> Identifying molecular and cellular features associated with resistance to
      targeted BRAF/MAPK pathway inhibition may guide development of novel therapeutic
      approaches. Integrated, comparative analysis of genomic and functional data in
      sensitive and resistant cell lines unveils novel targetable regulators of
      resistance to MAPK pathway inhibition in melanoma. Cancer Discov; 7(8); 799-801.
      (c)2017 AACR.See related article by Eskiocak et al., p. 832.

PMID- 28765116
TI  - Bap1 and Pbrm1: Determinants of Tumor Grade and mTOR Activation in VHL-Deficient
      Mouse Models of Renal Cell Carcinoma.
AB  - <b/> Large genome sequencing efforts have identified frequent mutations in the
      histone-modifying and chromatin-remodeling genes BAP1 and PBRM1 in clear cell
      renal cell carcinoma (ccRCC). In this issue of Cancer Discovery, Gu and
      colleagues model these genetic events in mice and report that dual inactivation
      of Vhl with either Bap1 or Pbrm1 results in faithful genetically engineered
      murine models of ccRCC. Moreover, their work establishes that Bap1 and Pbrm1 are
      determinants of tumor grade and mTORC1 activation and provocatively suggests that
      the cell of origin of ccRCC may lie in PAX8-expressing Bowman capsule cells.
      Cancer Discov; 7(8); 802-4. (c)2017 AACRSee related article by Gu et al., p. 900.

PMID- 28765117
TI  - NICE guidelines could put 12 million UK adults on statins.

PMID- 28765118
TI  - Effects of electroacupuncture to the trigeminal nerve area on the autonomic
      nervous system and cerebral blood flow in the prefrontal cortex.
AB  - BACKGROUND: The autonomic nervous system and trigeminal nerve are involved in
      adjusting flow through diverging cerebral arteries in the prefrontal cortex. The
      purpose of this study was to examine the effect of 100 Hz electroacupuncture (EA)
      to the trigeminal nerve area on cerebral blood flow and autonomic nervous system
      function. METHOD: This was a randomised crossover study of 16 healthy volunteers
      who were assigned to an EA or control group. Stimulation (in the EA group) was
      performed five times, each after 1 min of rest. Needles were inserted at the
      inner edge of the eyebrows and 1 cm from the front hairline midpoint. We used
      high-frequency (HF) and low-frequency (LF) components of heart rate (HR)
      variability to assess autonomic nervous system function. HF and LF/HF ratio were
      taken as indicators of parasympathetic and sympathetic nervous system activity,
      respectively. We measured cerebral blood flow using a two-channel near-infrared
      spectroscope. RESULTS: In the EA group, HR significantly decreased (p=0.004) and
      HF significantly increased (p=0.006) relative to baseline. By contrast, there
      were no significant changes in HR or HF within the control group (p>0.05).
      Accordingly, HR tended to be lower (p=0.087) and HF greater (p=0.071) in the EA
      group versus the control group. There were no significant differences in LF/HF
      ratio within/between groups. Compared with the control group, cerebral blood flow
      was significantly greater in the left (p=0.048) and right (p=0.016) prefrontal
      cortex in the EA group. CONCLUSIONS: Delivery of 100 Hz EA to the trigeminal
      nerve area reduces HR and increases parasympathetic nervous activity and cerebral
      blood flow.

PMID- 28765121
TI  - Novel therapies for immune-mediated inflammatory diseases: What can we learn from
      their use in rheumatoid arthritis, spondyloarthritis, systemic lupus
      erythematosus, psoriasis, Crohn's disease and ulcerative colitis?
AB  - The past three decades have witnessed remarkable advances in our ability to
      target specific elements of the immune and inflammatory response, fuelled by
      advances in both biotechnology and disease knowledge. As well as providing
      superior treatments for immune-mediated inflammatory diseases (IMIDs), such
      therapies also offer unrivalled opportunities to study the underlying
      immunopathological basis of these conditions.In this review, we explore recent
      approaches to the treatment of IMIDs and the insights to pathobiology that they
      provide. We review novel biologic agents targeting the T-helper 17 axis,
      including therapies directed towards interleukin (IL)-17 (secukinumab,
      ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab,
      briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab,
      mirikizumab). We also present an overview of biologics active against type I and
      II interferons, including sifalumumab, rontalizumab, anifrolumab and
      fontolizumab. Emerging strategies to interfere with cellular adhesion processes
      involved in lymphocyte recruitment are discussed, including both integrin
      blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate
      receptor inhibition (fingolimod, ozanimod). We summarise the development and
      recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs,
      including first-generation pan-JAK inhibitors (tofacitinib, baricitinib,
      ruxolitinib, peficitinib) and second-generation selective JAK inhibitors
      (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells
      (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development
      of novel strategies for regulatory T-cell modulation (including low-dose IL-2
      therapy and Tregitopes) are also discussed. Finally, we explore recent
      biotechnological advances such as the development of bispecific antibodies (ABT
      122, COVA322), and their application to the treatment of IMIDs.

PMID- 28765120
TI  - Constitutive IDO1 Expression in Human Tumors Is Driven by Cyclooxygenase-2 and
      Mediates Intrinsic Immune Resistance.
AB  - Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX
      2) expression may be a driver of immune suppression in melanoma, but the
      mechanisms involved remain elusive. Here, we show that COX-2 expression drives
      constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor
      cells. IDO1 is an immunosuppressive enzyme that degrades tryptophan. In a series
      of seven human tumor lines, constitutive IDO1 expression depends on COX-2 and
      prostaglandin E2 (PGE2), which, upon autocrine signaling through the EP receptor,
      activates IDO1 via the PKC and PI3K pathways. COX-2 expression itself depends on
      the MAPK pathway, which therefore indirectly controls IDO1 expression. Most of
      these tumors carry PI3K or MAPK oncogenic mutations, which may favor constitutive
      IDO1 expression. Celecoxib treatment promoted immune rejection of IDO1-expressing
      human tumor xenografts in immunodeficient mice reconstituted with human
      allogeneic lymphocytes. This effect was associated with a reduced expression of
      IDO1 in those ovarian SKOV3 tumors and an increased infiltration of CD3+ and CD8+
      cells. Our results highlight the role of COX-2 in constitutive IDO1 expression by
      human tumors and substantiate the use of COX-2 inhibitors to improve the efficacy
      of cancer immunotherapy, by reducing constitutive IDO1 expression, which
      contributes to the lack of T-cell infiltration in "cold" tumors, which fail to
      respond to immunotherapy. Cancer Immunol Res; 5(8); 695-709. (c)2017 AACR.

PMID- 28765122
TI  - Impact of age and sex on the incidence and prevalence of psoriatic arthritis.

PMID- 28765123
TI  - Rising indemnity fees could lead to worst ever winter crisis, says new GP leader.

PMID- 28765124
TI  - Demographic and behavioural risk factors associated with Trichomonas vaginalis
      among South African HIV-positive men with genital ulcer disease: a cross
      sectional study.
AB  - OBJECTIVES: Demographic and risky sexual behaviours may increase the risk for
      Trichomonas vaginalis (TV) infection and, thus, enhance HIV transmission to
      uninfected partners. We assessed the demographic and behavioural risk factors
      associated with TV among South African HIV-positive men with genital ulcer
      disease. METHODS: We conducted a cross-sectional study with data from a
      randomised controlled trial conducted by the Centers for Disease Control and
      Prevention and the London School of Hygiene and Tropical Medicine. The data were
      obtained from three primary healthcare clinics in South Africa. At baseline
      (n=387), participants reported on demographics, sexual behaviour, history of
      sexually transmitted infections and clinical ulcers. The outcome TV was measured
      using real-time multiplex PCR assays and a Rotor-gene 3000 platform from the
      first and past urine samples of all participants. Logistic regression model
      estimated ORs and 95% CIs adjusted for demographics, sexual risk behaviours and
      ulcer conditions. RESULTS: An estimated 11.4% of TV was detected among the men.
      The odds of TV infection were significantly associated with high blister counts
      (OR 4.0, 95% CI 1.6 to 28, p=0.01), ulcer pain (OR 0.4, 95% CI 0.2 to 0.7,
      p=0.003), number of days with ulcers (OR 0.4, 95% CI 0.2 to 0.8, p=0.006), sought
      treatment before coming into clinics (OR 0.07, 95% CI 0.002 to 0.7, p=0.005) and
      being unqualified worker (OR 2.5, 95% CI 0.9 to 6.7 p=0.05). Multivariate
      analyses revealed that increased days with ulcers (OR 0.1, 95% CI 0.04 to 0.5,
      p=0.002) and ulcer pain intensity (OR 0.08, 95% CI 0.007 to 1.1, p=0.05) remained
      significantly associated with decreased odds of TV infection. Men from the Sotho
      ethnic group were eight times more likely to have TV infection (OR 8.6, 95% CI
      1.3 to 55.7, p<0.02) than men from the other ethnic groups. CONCLUSION: HIV
      positive men with severe ulceration should be screened and treated for TV to
      minimise HIV transmission to uninfected partners.

PMID- 28765125
TI  - Sepsis and Critical Illness Research Center investigators: protocols and standard
      operating procedures for a prospective cohort study of sepsis in critically ill
      surgical patients.
AB  - INTRODUCTION: Sepsis is a common, costly and morbid cause of critical illness in
      trauma and surgical patients. Ongoing advances in sepsis resuscitation and
      critical care support strategies have led to improved in-hospital mortality.
      However, these patients now survive to enter state of chronic critical illness
      (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven
      by the persistent inflammation, immunosuppression and catabolism syndrome (PICS).
      The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a
      platform by which the prevalence and pathogenesis of CCI and PICS may be
      understood at a mechanistic level across multiple medical disciplines, leading to
      the development of novel management strategies and targeted therapies. METHODS:
      Here, we describe the design, study cohort and standard operating procedures used
      in the prospective study of human sepsis at a level 1 trauma centre and tertiary
      care hospital providing care for over 2600 critically ill patients annually.
      These procedures include implementation of an automated sepsis surveillance
      initiative, augmentation of clinical decisions with a computerised sepsis
      protocol, strategies for direct exportation of quality-filtered data from the
      electronic medical record to a research database and robust long-term follow-up.
      ETHICS AND DISSEMINATION: This study has been registered at ClinicalTrials.gov,
      approved by the University of Florida Institutional Review Board and is actively
      enrolling subjects. Dissemination of results is forthcoming.

PMID- 28765126
TI  - Cost-utility and budget impact analyses of the use of NEPA for chemotherapy
      induced nausea and vomiting prophylaxis in Italy.
AB  - OBJECTIVE: To evaluate the efficiency of resources allocation and sustainability
      of the use of netupitant+palonosetron (NEPA) for chemotherapy-induced nausea and
      vomiting (CINV) prophylaxis assuming the Italian National Health Service (NHS)
      perspective. A published Markov model was adapted to assess the incremental cost
      utility ratio of NEPA compared with aprepitant (APR) + palonosetron (PALO),
      fosaprepitant (fAPR) + PALO, APR + ondansetron (ONDA), fAPR + ONDA in patients
      receiving a highly emetogenic chemotherapy (HEC) and with APR + PALO and fAPR +
      PALO in patients receiving a moderately emetogenic chemotherapy (MEC). SETTING:
      Oncology hospital department in Italy. METHODS: A Markov model was used to
      determine the impact of NEPA on the budget of the Italian NHS on a 5-day time
      horizon, corresponding to the acute and delayed CINV prophylaxis phases. Direct
      medical costs considered were related to antiemetic drugs, adverse events
      management, CINV episodes management. Clinical and quality of life data referred
      to previously published works. The budget impact analysis considered the
      aforementioned therapies plus PALO alone (for HEC and MEC) on a 5-year time
      horizon, comparing two scenarios: one considering the use of NEPA and one not
      considering its use. PRIMARY AND SECONDARY OUTCOME MEASURES: Incremental cost per
      quality adjusted life year (QALY) and differential economic impact for the
      Italian NHS between the two scenarios considered. RESULTS: NEPA is more effective
      and less expensive (dominant) compared with APR + PALO (for HEC and MEC), fAPR +
      PALO (for HEC and MEC), APR + ONDA (for HEC), fAPR + ONDA (for HEC). The use of
      NEPA would lead to a 5-year cost decrease of ?63.7 million (?42.7 million for HEC
      and ?20.9 million for MEC). CONCLUSIONS: NEPA allows an efficient allocation of
      resources for the Italian NHS and it is sustainable, leading to a cost decrease
      compared with a scenario which does not consider its use.

PMID- 28765127
TI  - Neighbouring green space and mortality in community-dwelling elderly Hong Kong
      Chinese: a cohort study.
AB  - OBJECTIVE: Green space has been shown to be beneficial for human wellness through
      multiple pathways. This study aimed to explore the contributions of neighbouring
      green space to cause-specific mortality. METHODS: Data from 3544 Chinese men and
      women (aged >=65 years at baseline) in a community-based cohort study were
      analysed. Outcome measures, identified from the death registry, were death from
      all-cause, respiratory system disease, circulatory system disease. The quantity
      of green space (%) within a 300 m radius buffer was calculated for each subject
      from a map created based on the Normalised Difference Vegetation Index. Cox
      proportional hazard models adjusted for demographics, socioeconomics, lifestyle,
      health conditions and housing type were used to estimate the HRs and 95% CIs.
      RESULTS: During a mean of 10.3 years of follow-up, 795 deaths were identified.
      Our findings showed that a 10% increase in coverage of green space was
      significantly associated with a reduction in all-cause mortality (HR 0.963, 95%
      CI 0.930 to 0.998), circulatory system-caused mortality (HR 0.887, 95% CI 0.817
      to 0.963) and stroke-caused mortality (HR 0.661, 95% CI 0.524 to 0.835),
      independent of age, sex, marital status, years lived in Hong Kong, education
      level, socioeconomic ladder, smoking, alcohol intake, diet quality, self-rated
      health and housing type. The inverse associations between coverage of green space
      with all-cause mortality (HR 0.964, 95% CI 0.931 to 0.999) and circulatory system
      disease-caused mortality (HR 0.888, 95% CI 0.817 to 0.964) were attenuated when
      the models were further adjusted for physical activity and cognitive function.
      The effects of green space on all-cause and circulatory system-caused mortality
      tended to be stronger in females than in males. CONCLUSION: Higher coverage of
      green space was associated with reduced risks of all-cause mortality, circulatory
      system-caused mortality and stroke-caused mortality in Chinese older people
      living in a highly urbanised city.

PMID- 28765128
TI  - Insurance status, inhospital mortality and length of stay in hospitalised
      patients in Shanxi, China: a cross-sectional study.
AB  - OBJECTIVES: To determine insurance-related disparities in hospital care for
      patients with acute myocardial infarction (AMI), heart failure (HF) and
      pneumonia. SETTING AND PARTICIPANTS: A total of 22 392 patients with AMI, 8056
      patients with HF and 17 161 patients with pneumonia were selected from 31
      tertiary hospitals in Shanxi, China, from 2014 to 2015 using the International
      Classification of Diseases, Tenth Revision codes. Patients were stratified by
      health insurance status, namely, urban employee-based basic medical insurance
      (UEBMI), urban resident-based basic medical insurance (URBMI), new cooperative
      medical scheme (NCMS) and self-payment. OUTCOME MEASURES: Inhospital mortality
      and length of stay (LOS). RESULTS: The highest unadjusted inhospital mortality
      rate was detected in NCMS patients independent of medical conditions (4.7%, 4.4%
      and 11.1% for AMI, HF and pneumonia, respectively). The lowest unadjusted
      inhospital mortality rate and the longest LOS were observed in UEBMI patients.
      After controlling patient-level and hospital-level covariates, the adjusted
      inhospital mortality was significantly higher for NCMS and self-payment among
      patients with AMI, for NCMS among patients with HF and for URBMI, NCMS and self
      payment among patients with pneumonia compared with UEBMI. The LOS of the URBMI,
      NCMS and self-payment groups was significantly shorter than that of the UEBMI
      group. CONCLUSION: Insurance-related disparities in hospital care for patients
      with three common medical conditions were observed in this study. NCMS patients
      had significantly higher adjusted inhospital mortality and shorter LOS compared
      with UEBMI patients. Policies on minimising the disparities among different
      insurance schemes should be established by the government.

PMID- 28765129
TI  - Medical school selection criteria as predictors of medical student empathy: a
      cross-sectional study of medical students, Ireland.
AB  - OBJECTIVES: To determine whether performance in any of the Health Professions
      Admissions Test (HPAT) sections, most specifically the interpersonal
      understanding section, correlates with self-reported empathy levels in medical
      students. SETTING: The study was conducted in University College Cork, Ireland.
      PARTICIPANTS: 290 students participated in the study. Matching HPAT scores were
      available for 263 students. All male and female undergraduate students were
      invited to participate. Postgraduate and international students were excluded.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Primary measures: HPAT-Ireland and
      Jefferson Scale of Physician Empathy (JSE) scores were compared including
      subsection analysis. Secondary measures: comparisons were made between groups
      such as gender and year of programme. RESULTS: A total of 290 students
      participated. Males scored significantly higher than females for total HPAT
      Ireland (U=7329, z=-2.04, p<0.05), HPAT-Ireland section 1 (U=5382, z=-5.21,
      p<0.001) and section 3 scores (U=6833, z=-2.85, p<0.01). In contrast, females
      scored significantly higher than males on HPAT-Ireland section 2 (U=5844, z=
      4.46, p<0.001). Females demonstrated significantly higher total JSE scores
      relative to males (mean score +/- SEM: 113.33+/-1.05vs 109.21+/-0.95; U=8450, z=
      2.83, p<0.01). No significant association was observed between JSE scores and any
      of the HPAT-Ireland measures (all p>0.05). There was no effect of programme year
      on JSE scores (all p>0.05). CONCLUSION: The introduction of the HPAT-Ireland test
      was partly designed to identify students with strong interpersonal skills. A
      significant finding of this study is that JSE values did not correlate with HPAT
      Ireland scores. This study suggests no clear link between scores on a selection
      test, the HPAT-Ireland, which is designed to assess several skill domains
      including interpersonal skills, and scores on a psychometric measure of empathy,
      at any point during medical education.

PMID- 28765130
TI  - The child's perspective on discomfort during medical research procedures: a
      descriptive study.
AB  - OBJECTIVE: The evaluation of discomfort in paediatric research is scarcely
      evidence-based. In this study, we make a start in describing children's self
      reported discomfort during common medical research procedures and compare this
      with discomfort during dental check-ups which can be considered as a reference
      level of a 'minimal discomfort' medical procedure. We exploratory study whether
      there are associations between age, anxiety-proneness, gender, medical condition,
      previous experiences and discomfort. We also describe children's suggestions for
      reducing discomfort. DESIGN: Cross-sectional descriptive study. SETTING:
      Paediatric research at three academic hospitals. PATIENTS: 357 children with and
      without illnesses (8-18 years, mean=10.6 years) were enrolled: 307 from
      paediatric research studies and 50 from dental care. MAIN OUTCOME MEASURES: We
      measured various generic forms of discomfort (nervousness, annoyance, pain,
      fright, boredom, tiredness) due to six common research procedures: buccal swabs,
      MRI scans, pulmonary function tests, skin prick tests, ultrasound imaging and
      venepunctures. RESULTS: Most children reported limited discomfort during the
      research procedures (means: 1-2.6 on a scale from 1 to 5). Compared with dental
      check-ups, buccal swab tests, skin prick tests and ultrasound imaging were less
      discomforting, while MRI scans, venepunctures and pulmonary function tests caused
      a similar degree of discomfort. 60.3% of the children suggested providing
      distraction by showing movies to reduce discomfort. The exploratory analyses
      suggested a positive association between anxiety-proneness and discomfort.
      CONCLUSIONS: The findings of this study support the acceptability of
      participation of children in the studied research procedures, which stimulates
      evidence-based research practice. Furthermore, the present study can be
      considered as a first step in providing benchmarks for discomfort of procedures
      in paediatric research.

PMID- 28765131
TI  - Discontinuation and non-publication of randomised clinical trials supported by
      the main public funding body in Switzerland: a retrospective cohort study.
AB  - OBJECTIVE: The Swiss National Science Foundation (SNSF) promotes academic
      excellence through competitive selection of study proposals and rigorous
      evaluation of feasibility, but completion status and publication history of SNSF
      supported randomised clinical trials (RCTs) remain unclear. The main objectives
      were to review all healthcare RCTs supported by the SNSF for trial
      discontinuation and non-publication, to investigate potential risk factors for
      trial discontinuation due to poor recruitment and non-publication, and to compare
      findings to other Swiss RCTs not supported by the SNSF. DESIGN: We established a
      retrospective cohort of all SNSF-supported RCTs for which recruitment and funding
      had ended in 2015 or earlier. For each RCT, two investigators independently
      searched corresponding publications in electronic databases. In addition, we
      approached all principal investigators to ask for additional publications and
      information about trial discontinuation. Teams of two investigators independently
      extracted details about study design, recruitment of participants, outcomes,
      analysis and sample size from the original proposal and, if available, from trial
      registries and publications. We used multivariable regression analysis to explore
      potential risk factors associated with discontinuation due to poor recruitment
      and with non-publication, and to compare our results with data from a previous
      cohort of Swiss RCTs not supported by the SNSF. RESULTS: We included 101 RCTs
      supported by the SNSF between 1986 and 2015. Eighty-seven (86%) principal
      investigators responded to our survey. Overall, 69 (68%) RCTs were completed, 26
      (26%) RCTs were prematurely discontinued (all due to slow recruitment) and the
      completion status remained unclear for 6 (6%) RCTs. For analysing publication
      status, we excluded 4 RCTs for which follow-up was still ongoing and 9 for which
      manuscripts were still in preparation. Of the remaining 88 RCTs, 53 (60%) were
      published as full articles in peer-reviewed journals. Multivariable regression
      models suggested that discontinued trials were at higher risk for non-publication
      than completed trials (adjusted OR 7.61; 95% CI 2.44 to 27.09). Compared with
      other Swiss RCTs, the risk of discontinuation for SNSF-supported RCTs was higher
      than in industry-initiated RCTs (adjusted OR 3.84; 95% CI 1.68 to 8.74), but not
      significantly different from investigator-initiated RCTs not supported by the
      SNSF (adjusted OR 1.05; 95% CI 0.51 to 2.11). We found no evidence that the
      proportion of discontinued or unpublished RCTs decreased over the last 20 years.
      CONCLUSIONS: One out of four SNSF-supported RCTs were prematurely discontinued
      due to slow recruitment, 40% of all included RCTs and 70% of all discontinued
      RCTs were not published in peer-reviewed journals. There is a case to reconsider
      how public funding bodies such as the SNSF could improve their feasibility
      assessment and promote publication of RCTs irrespective of completion status.

PMID- 28765132
TI  - A systematic review to identify and assess the effectiveness of alternatives for
      people over the age of 65 who are at risk of potentially avoidable hospital
      admission.
AB  - BACKGROUND/OBJECTIVES: There are some older patients who are 'at the decision
      margin' of admission. This systematic review sought to explore this issue with
      the following objective: what admission alternatives are there for older patients
      and are they safe, effective and cost-effective? A secondary objective was to
      identify the characteristics of those older patients for whom the decision to
      admit to hospital may be unclear. DESIGN: Systematic review of controlled studies
      (April 2005-December 2016) with searches in Medline, Embase, Cinahl and CENTRAL
      databases. The protocol is registered at PROSPERO (CRD42015020371). Studies were
      assessed using Cochrane risk of bias criteria, and relevant reviews were assessed
      with the AMSTAR tool. The results are presented narratively and discussed.
      SETTING: Primary and secondary healthcare interface. PARTICIPANTS: People aged
      over 65 years at risk of an unplanned admission. INTERVENTIONS: Any community
      based intervention offered as an alternative to admission to an acute hospital.
      PRIMARY AND SECONDARY OUTCOMES MEASURES: Reduction in secondary care use, patient
      related outcomes, safety and costs. RESULTS: Nineteen studies and seven
      systematic reviews were identified. These recruited patients with both specific
      conditions and mixed chronic and acute conditions. The interventions involved
      paramedic/emergency care practitioners (n=3), emergency department-based
      interventions (n=3), community hospitals (n=2) and hospital-at-home services
      (n=11). Data suggest that alternatives to admission appear safe with potential to
      reduce secondary care use and length of time receiving care. There is a lack of
      patient-related outcomes and cost data. The important features of older patients
      for whom the decision to admit is uncertain are: age over 75 years,
      comorbidities/multi-morbidities, dementia, home situation, social support and
      individual coping abilities. CONCLUSIONS: This systematic review describes and
      assesses evidence on alternatives to acute care for older patients and shows that
      many of the options available are safe and appear to reduce resource use.
      However, cost analyses and patient preference data are lacking.

PMID- 28765133
TI  - Balance deficiencies in women with fibromyalgia assessed using computerised
      dynamic posturography: a cross-sectional study in Spain.
AB  - OBJECTIVES: Our aims were (1) to compare the sensory organisation of balance
      control and balance strategies between women with fibromyalgia (FM) and healthy
      women; (2) to investigate which sensory component, that is, vestibular, visual or
      somato-sensory, is the most affected in FM and (3) to determine the associations
      between the functional independence measure (FIM) and balance responses in FM.
      DESIGN: Cross-sectional observational study. SETTING: Urban regional hospital and
      university (Universidad Rey Juan Carlos, Madrid, Spain). PARTICIPANTS: Twenty
      women with FM and 20 matched healthy women. PRIMARY/SECONDARY OUTCOME MEASURES:
      The sensory organisation test (SOT) was used to determine postural sway and
      balance during six different conditions with subjects in a standing position. The
      FIM was used to determine the level of functional independence in daily life
      activities (ADL). Between-group differences were analysed with analysis of
      covariance, and the Spearman's test was used for correlations. RESULTS:
      Significant differences between-groups and between-conditions were found for all
      SOT conditions (all, p<0.001): women with FM showed lower scores being the
      vestibular score the most affected. Different correlations between SOT conditions
      and some specific ADL were observed in the FM group: bathing activity and balance
      condition 6 (rs=0.541; p<0.001), bed transfers activity and conditions 2
      (rs=0.491; p<0.001) and 3 (rs=0.510; p<0.001), positioning strategy six and
      dressing the upper (rs=0.530; p<0.001) or lower (rs=0.562; p<0.001) body, and
      toileting (rs=0.521; p<0.001): the greater the loss of balance, the greater the
      interference on some daily life activities. CONCLUSIONS: Women with FM exhibited
      balance deficiencies and used different strategies for maintaining their balance
      in standing, which was associated with a negative impact on functional
      independence.

PMID- 28765134
TI  - Incidence and prevalence of diabetic ketoacidosis (DKA) among adults with type 1
      diabetes mellitus (T1D): a systematic literature review.
AB  - OBJECTIVES: To summarise incidence and prevalence of diabetic ketoacidosis (DKA)
      in adults with type 1 diabetes (T1D) for the overall patient population and
      different subgroups (age, sex, geographical region, ethnicity and type of insulin
      administration). DESIGN: Systematic literature review (SLR). DATA SOURCES:
      Medline (via PubMed) and Embase (1 January 2000 to 23 June 2016). STUDY
      SELECTION: Peer-reviewed observational studies with reported data on the
      incidence or prevalence of DKA in T1D adults were included. A single reviewer
      completed the study screening and selection process and a second reviewer
      performed an additional screening of approximately 20% of the publications; two
      reviewers independently conducted the quality assessment; the results were
      narratively synthesised. RESULTS: Out of 1082 articles, 19 met the inclusion and
      exclusion criteria, with two additional studies identified that did not specify
      the patient age range and are therefore not included in the SLR. Overall, eight
      studies reported incidence with a range of 0-56 per 1000 person-years (PYs), with
      one outlying study reporting an incidence of 263 per 1000 PYs. Eleven studies
      reported prevalence with a range of 0-128 per 1000 people. Prevalence of DKA
      decreased with increasing age. Subgroup analyses were performed using data from
      no more than two studies per subgroup. There was a higher prevalence of DKA
      reported in women, non-whites and patients treated with insulin injections
      compared with men, whites and patients using continuous subcutaneous insulin
      infusion pumps, respectively. CONCLUSIONS: To our knowledge, this is the first
      SLR on the epidemiology of DKA in T1D adults. Despite an increasing prevalence of
      T1D in recent years, DKA in adults has been poorly characterised. In an era when
      the benefit-risk profiles of new antidiabetic therapies are being evaluated,
      including the potential risk of DKA, there is a clear need to better elucidate
      the expected rate of DKA among T1D adults.

PMID- 28765135
TI  - Prevalence and correlates of symptoms of post-traumatic stress disorder among
      Chinese healthcare workers exposed to physical violence: a cross-sectional study.
AB  - OBJECTIVES: Post-traumatic stress disorder (PTSD) is a common psychological
      maladjustment to undergoing a traumatic event. Our aim was to measure the
      prevalence of PTSD among Chinese healthcare workers exposed to physical violence'
      and explore the associations of their demographic characteristics, social
      support, personality traits' and coping styles with their PTSD symptoms. METHODS:
      A cross-sectional study was conducted using the Workplace Violence Scale,
      Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Social Support
      Rating Scale (SSRS), Eysenck Personality Questionnaire-Revised Short Scale and
      Trait Coping Style Questionnaire. We used convenience sampling method to collect
      data from March 2015 to September 2016. Healthcare workers (n=2706) from 39
      public hospitals located in Heilongjiang, Hebei and Beijing provinces of China
      completed the questionnaires (effective response rate=84.25%). RESULTS: Overall,
      the prevalence of physical violence in the previous 12 months was 13.60%
      (n=2706). The prevalence of PTSD among the healthcare workers who experienced
      physical violence was 28.0% (n=368). Most of the victims of physical violence
      (50.80%) did not exhibit PTSD symptoms based on their PCL-C scores, and 47.0% did
      not manifest the diagnostic criteria for PTSD after experiencing physical
      violence. The level of PTSD symptoms was negatively correlated with their scores
      on the SSRS (r=-0.188, p<0.001). The hierarchical regression analysis (block 3)
      revealed that, in women, positive coping was significantly associated with PTSD
      symptoms (beta=-0.376, p=0.001). However, the effect of positive coping was not
      significant in men. CONCLUSIONS: The results suggest that the aftermath of
      physical violence contributes to the current prevalence of PTSD. The positive
      effects of social support on PTSD symptoms suggest that it has practical
      implications for interventions to promote psychological health. The healthcare
      workers' coping styles influenced the development of PTSD symptoms. Therefore,
      adopting effective coping styles and receiving social support have potential
      roles in the recovery from trauma after experiencing physical violence.

PMID- 28765136
TI  - Internet-based support for self-management strategies for people with COPD
      protocol for a controlled pragmatic pilot trial of effectiveness and a process
      evaluation in primary healthcare.
AB  - INTRODUCTION: The use of adequate self-management strategies for people with
      chronic obstructive pulmonary disease (COPD) reduces healthcare use, improves
      health-related quality of life (HRQoL) and recovery after acute exacerbations.
      However, not many people with COPD receive support that promotes the use of such
      strategies and therefore new methods to facilitate and promote the use of self
      management strategies are highly warranted. This pilot trial aims to evaluate the
      feasibility of the study design and study procedures considering effectiveness of
      the novel intervention, the COPD-web. METHODS AND ANALYSIS: The overall design is
      a pragmatic controlled pilot trial with preassessments and postassessments and a
      parallel process evaluation. Patients with the diagnosis of COPD will be eligible
      for the study. The intervention group will be recruited when visiting one of the
      six participating primary care units in Sweden. The control group will be
      identified from the unit's computerised registers. The intervention, the COPD
      web, is an interactive web page with two sections; one directed at people with
      COPD and one at healthcare professionals. The sections aim to support patients'
      self-management skills-and to facilitate the provision of support for self
      management strategies, respectively. Effectiveness with regard to patients'
      symptoms, HRQoL, knowledge of and readiness for COPD-related self-management,
      health literacy, self-efficacy for physical activity and time spent in physical
      activity and time being sedentary, and further, healthcare professionals'
      knowledge of and readiness to support COPD-related self-management strategies
      will be assessed using questionnaires at 3 and 12 months. The process evaluation
      will include observations and interviews. ETHICS AND DISSEMINATION: Ethical
      approval has been obtained. Findings will be presented at conferences, submitted
      for publication in peer-reviewed publications and presented to the involved
      healthcare professionals, patients and to patient organisations. TRIAL
      REGISTRATION NUMBER: ClinicalTrials.gov: NCT02696187.

PMID- 28765137
TI  - Childhood respiratory illness presentation and service utilisation in primary
      care: a six-year cohort study in Wellington, New Zealand, using natural language
      processing (NLP) software.
AB  - OBJECTIVES: To identify childhood respiratory tract-related illness presentation
      rates and service utilisation in primary care by interrogating free text and
      coded data from electronic medical records. DESIGN: Retrospective cohort study.
      Data interrogation used a natural language processing software inference
      algorithm. SETTING: 36 primary care practices in New Zealand. Data analysed from
      January 2008 to December 2013. PARTICIPANTS: The records from 77 582 children
      enrolled were reviewed over a 6-year period to estimate the presentation of
      childhood respiratory illness and service utilisation. This cohort represents 268
      919 person-years of data and over 650 000 unique consultations. MAIN OUTCOME
      MEASURE: Childhood respiratory illness presentation rate to primary care
      practice, with description of seasonal and yearly variation. RESULTS: Respiratory
      conditions constituted 46% of all child-general practitioner consultations with a
      stable year-on-year pattern of seasonal peaks. Upper respiratory tract infection
      was the most common respiratory category accounting for 21.0% of all childhood
      consultations, followed by otitis media (12.2%), wheeze-related illness (9.7%),
      throat infection (7.4%) and lower respiratory tract infection (4.4%). Almost 70%
      of children presented to their general practitioner with at least one respiratory
      condition in their first year of life; this reduced to approximately 25% for
      children aged 10-17. CONCLUSION: This is the first study to assess the primary
      care incidence and service utilisation of childhood respiratory illness in a
      large primary care cohort by interrogating electronic medical record free text.
      The study identified the very high primary care workload related to childhood
      respiratory illness, especially during the first 2 years of life. These data can
      enable more effective planning of health service delivery. The findings and
      methodology have relevance to many countries, and the use of primary care 'big
      data' in this way can be applied to other health conditions.

PMID- 28765138
TI  - Attitudes on cost-effectiveness and equity: a cross-sectional study examining the
      viewpoints of medical professionals.
AB  - OBJECTIVE: To determine the attitudes of physicians and trainees in regard to the
      roles of both cost-effectiveness and equity in clinical decision making. DESIGN:
      In this cross-sectional study, electronic surveys containing a hypothetical
      decision-making scenario were sent to medical professionals to select between two
      colon cancer screening tests for a population. SETTING: Three Greater Boston
      academic medical institutions: Tufts University School of Medicine, Tufts Medical
      Centre and Lahey Hospital and Medical Centre. PARTICIPANTS: 819 medical students,
      497 residents-in-training and 671 practising physicians were contacted
      electronically using institutional and organisational directories. MAIN OUTCOMES
      AND MEASURES: Stratified opinions of medical providers and trainee subgroups
      regarding cost-effectiveness and equity. RESULTS: A total of 881 respondents
      comprising 512 medical students, 133 medical residents-in-training and 236
      practising physicians completed the survey (total response rate 44.3%). Thirty
      six per cent of medical students, 44% of residents-in-training and 53% of
      practising physicians favoured the less effective and more equitable screening
      test. Residents-in-training (OR 1.49, CI 1.01 to 2.21; p=0.044) and practising
      physicians (OR 2.12, CI 1.54 to 2.92; p<0.001) were more likely to favour the
      equitable option compared with medical students. Moreover, female responders
      across all three cohorts favoured the more equitable screening test to a greater
      degree than did male responders (OR 1.70, CI 1.29 to 2.24; p<0.001). CONCLUSIONS:
      Cost-effectiveness analysis does not accurately reflect the importance that
      medical professionals place on equity. Among medical professionals, practising
      physicians appear to be more egalitarian than residents-in-training, while
      medical students appear to be most utilitarian and cost-effective. Meanwhile,
      female respondents in all three cohorts favoured the more equitable option to a
      greater degree than their male counterparts. Healthcare policies that trade off
      equity in favour of cost-effectiveness may be unacceptable to many medical
      professionals, especially practising physicians and women.

PMID- 28765139
TI  - The use of feasibility studies for stepped-wedge cluster randomised trials:
      protocol for a review of impact and scope.
AB  - INTRODUCTION: The stepped-wedge cluster randomised trial (SW-CRT) is a complex
      design, for which many decisions about key design parameters must be made during
      the planning. These include the number of steps and the duration of time needed
      to embed the intervention. Feasibility studies are likely to be useful for
      informing these decisions and increasing the likelihood of the main trial's
      success. However, the number of feasibility studies being conducted for SW-CRTs
      is currently unknown. This review aims to establish the number of feasibility
      studies being conducted for SW-CRTs and determine which feasibility issues are
      commonly investigated. METHODS AND ANALYSIS: Fully published feasibility studies
      for SW-CRTs will be identified, according to predefined inclusion criteria, from
      searches conducted in Ovid MEDLINE, Scopus, Embase and PsycINFO. To also identify
      and gain information on unpublished feasibility studies the following will be
      contacted: authors of published SW-CRTs (identified from the most recent
      systematic reviews); contacts for registered SW-CRTs (identified from clinical
      trials registries); lead statisticians of UK registered clinical trials units and
      researchers known to work in the area of SW-CRTs.Data extraction will be
      conducted independently by two reviewers. For the fully published feasibility
      studies, data will be extracted on the study characteristics, the rationale for
      the study, the process for determining progression to a main trial, how the study
      informed the main trial and whether the main trial went ahead. The researchers
      involved in the unpublished feasibility studies will be contacted to elicit the
      same information.A narrative synthesis will be conducted and provided alongside a
      descriptive analysis of the study characteristics. ETHICS AND DISSEMINATION: This
      review does not require ethical approval, as no individual patient data will be
      used. The results of this review will be published in an open-access peer
      reviewed journal.

PMID- 28765141
TI  - Meniscal resection may not benefit patients with traumatic meniscal tears.

PMID- 28765140
TI  - Clinical development of CAR T cells-challenges and opportunities in translating
      innovative treatment concepts.
AB  - Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint
      inhibition, has been celebrated as a breakthrough technology due to the
      substantial benefit observed in clinical trials with patients suffering from
      relapsed or refractory B-cell malignancies. In this review, we provide a
      comprehensive overview of the clinical trials performed so far worldwide and
      analyze parameters such as targeted antigen and indication, CAR molecular design,
      CAR T cell manufacturing, anti-tumor activities, and related toxicities. More
      than 200 CAR T cell clinical trials have been initiated so far, most of which aim
      to treat lymphoma or leukemia patients using CD19-specific CARs. An increasing
      number of studies address solid tumors as well. Notably, not all clinical trials
      conducted so far have shown promising results. Indeed, in a few patients CAR T
      cell therapy resulted in severe adverse events with fatal outcome. Of note, less
      than 10% of the ongoing CAR T cell clinical trials are performed in Europe.
      Taking lead from our analysis, we discuss the problems and general hurdles
      preventing efficient clinical development of CAR T cells as well as
      opportunities, with a special focus on the European stage.

PMID- 28765143
TI  - US plan gives greater role to electronic cigarettes in tobacco harm reduction.

PMID- 28765142
TI  - A retained intron in the 3'-UTR of Calm3 mRNA mediates its Staufen2- and activity
      dependent localization to neuronal dendrites.
AB  - Dendritic localization and hence local mRNA translation contributes to synaptic
      plasticity in neurons. Staufen2 (Stau2) is a well-known neuronal double-stranded
      RNA-binding protein (dsRBP) that has been implicated in dendritic mRNA
      localization. The specificity of Stau2 binding to its target mRNAs remains
      elusive. Using individual-nucleotide resolution CLIP (iCLIP), we identified
      significantly enriched Stau2 binding to the 3'-UTRs of 356 transcripts. In 28
      (7.9%) of those, binding occurred to a retained intron in their 3'-UTR The
      strongest bound 3'-UTR intron was present in the longest isoform of Calmodulin 3
      (Calm3L ) mRNA Calm3L 3'-UTR contains six Stau2 crosslink clusters, four of which
      are in this retained 3'-UTR intron. The Calm3L mRNA localized to neuronal
      dendrites, while lack of the 3'-UTR intron impaired its dendritic localization.
      Importantly, Stau2 mediates this dendritic localization via the 3'-UTR intron,
      without affecting its stability. Also, NMDA-mediated synaptic activity
      specifically promoted the dendritic mRNA localization of the Calm3L isoform,
      while inhibition of synaptic activity reduced it substantially. Together, our
      results identify the retained intron as a critical element in recruiting Stau2,
      which then allows for the localization of Calm3L mRNA to distal dendrites.

PMID- 28765144
TI  - Comparing optical coherence tomography findings in different aetiologies of
      infectious necrotising retinitis.
AB  - AIMS: To compare optical coherence tomography (OCT) features of active
      necrotising infectious retinitis (NIR) due to toxoplasmosis or herpesviruses and
      to determine distinctive OCT signs for these two causes of infectious retinitis.
      METHODS: OCT scans from eyes with active NIR due to varicella zoster virus (VZV),
      herpes simplex virus (HSV), cytomegalovirus (CMV), and toxoplasmosis (TOXO) were
      reviewed. All images were evaluated for the presence of previously described OCT
      findings in TOXO-NIR and compared with the viral group. New OCT findings were
      recorded and compared. Retinal and choroidal thickness were measured at the site
      of NIR and compared. RESULTS: 10 eyes diagnosed with TOXO-NIR and 13 eyes
      affected by viral-NIR (9 CMV and 4 VZV) were analysed. All eyes showed full
      thickness hyper-reflectivity, disruption of the retina and a variable degree of
      vitritis. Among previously described OCT signs, hyper-reflective oval deposits
      and hypo-reflectivity of the choroid had a higher prevalence in TOXO (p=0.018 and
      p<0.0001, respectively). Among the new signs, hyper-reflective round deposits
      along the posterior hyaloid, retrohyaloid hyper-reflective spots and a disruption
      of the choroidal architecture were more frequent in TOXO eyes (all p<0.01). Intra
      retinal oedema and hyper-reflective vertical strips within the outer nuclear
      layer were suggestive of a viral aetiology (p=0.045). Retinal thickness at the
      site of NIR did not differ between the two groups. Choroidal thickness was
      significantly higher in TOXO eyes (p=0.01). CONCLUSIONS: The diagnosis of NIR is
      largely based on clinical and laboratory findings. OCT changes may be useful in
      differentiating different causes of NIR.

PMID- 28765145
TI  - Optical coherence tomography angiography characterisation of Best disease and
      associated choroidal neovascularisation.
AB  - AIMS: To characterise the vasculature of the retina in patients with Best
      vitelliform dystrophy, including those with choroidal neovascularisation (CNV),
      using optical coherence tomography angiography (OCTA) and correlate with
      fluorescein angiography (FA). METHODS: This prospective observational study
      included 19 eyes of 10 patients with Best disease. Using OCTA, all layers of
      retina were qualitatively characterised for each eye. Patients with CNV also
      underwent FA, and areas of CNV were measured by OCTA and FA and correlated.
      RESULTS: Retinal characteristics revealed 14 (74%) eyes with abnormal foveal
      avascular zone (FAZ) in the superficial layer, 19 eyes (100%) had an abnormal FAZ
      in deep layers, 11 (58%) eyes had a hyper-reflective centre in the superficial
      layer, 18 (95%) had patchy vascularity loss in the deep layer, 17 (89%) eyes had
      hyporeflective centre in the choriocapillary (CC) layer and 12 (63%) of those
      eyes had hyper-reflective material within the hyporeflective centre. Also,
      notably 6 (86%) CNV eyes had a "halo" or a hypolucent area surrounded in the CNV
      complex in the outer retinal layer. CNV patterns resembled dense net, loose net,
      mixed and a new found pattern of a ring shape. CNV measurements revealed an
      average area of 1.66+/-1.18mm2 using OCTA and an average area of 0.88+/-0.76mm2
      using FA (p=0.15). CONCLUSION: OCTA reveals that eyes with Best disease have
      abnormal FAZ, patchy vascularity loss in the superficial and deep layers of the
      retina and capillary dropout with a hyporeflective centre in CC layer. Further,
      OCTA is superior to FA in measuring CNV.

PMID- 28765146
TI  - Reliability of Cyclotorsion measurements using Scanning Laser Ophthalmoscopy
      imaging in healthy subjects: the CySLO study.
AB  - BACKGROUND/AIMS: To evaluate inter-rater and intra-rater reliability of objective
      cyclotorsion measurements obtained in healthy subjects using the Heidelberg
      Spectralis spectral domain-optical coherence tomography (SD-OCT) device. METHODS:
      In this prospective methodological study, 32 healthy subjects (14 men, 18 women;
      aged 21-64 years) were enrolled, 31 right eyes were examined and their foveo
      papillary angles (FPAs) were measured. The retinal nerve fibre layer (RNFL)
      programme by Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany)
      was used to measure cyclotorsion based on the in-built algorithm for the
      measurement of the FPA on the scanning laser ophthalmoscopy (SLO) image. Repeated
      scans of the fixating and non-fixating right eye without and with eye tracker
      each were obtained by three different examiners. RESULTS: The mean FPA measured
      overall by all three examiners was 6.6 degrees +/-2.8 degrees . The inter-rater
      reliability of the measured FPAs using the linear mixed effects model is
      estimated as rhointer=0.8803. The intra-rater reliability is estimated as
      rhointra=0.9589. CONCLUSIONS: Repeatability of objective cyclotorsion
      measurements within and between observers using the Heidelberg Spectralis OCT is
      very high. SD-OCT/SLO imaging is a reliable imaging technique to measure and
      study cyclotorsion. CLINICAL TRIAL NUMBER: NCT02631369, Results.

PMID- 28765147
TI  - The association between ocular surface measurements with visual field reliability
      indices and gaze tracking results in preperimetric glaucoma.
AB  - BACKGROUND/AIMS: To investigate the relationship between gaze tracking (GT)
      results and ocular surface condition in glaucoma. METHOD: The Humphrey 24-2
      visual field (VF) was measured in 34 eyes of 30 patients with open-angle glaucoma
      without VF damage. Tear break-up time, Schirmer's test, tear meniscus volume
      (TMV) and presence of superficial punctate keratopathy (SPK) were also measured
      in order to describe the condition of the ocular surface. Various GT parameters
      were calculated: the average frequency of eye movements per stimulus between 1
      degrees  and 2 degrees  (move1-2), the average frequency of eye movements per
      stimulus between 3 degrees  and 5 degrees  (move3-5), the average frequency of
      eye movements per stimulus more than 6 degrees  (move>=6), the average tracking
      failure frequency per stimulus (TFF) and the average blinking frequency. The
      relationship between GT parameters, reliability indices and ocular surface
      measurements was investigated using linear mixed modelling. RESULTS: SPK was
      positively associated with high rates of move3-5 (coefficient=0.12 for SPK+,
      p=0.003) and move>=6 (coefficient=0.052 for SPK+, p=0.023). High TMV was
      significantly related to TFF (coefficient=0.37, p=0.023). Fixation losses, false
      positives and false-negatives were not significantly associated with any GT
      parameters or ocular surface measurements. CONCLUSION: SPK is associated with
      increased frequency of eye movements (move3-5 and move>=6). In addition, large
      TMV is associated with increased rate of TFF. Careful attention should be paid
      when interpreting GT parameters in patients with SPK or a large TMV.

PMID- 28765148
TI  - Changes in retinal venular oxygen saturation predict activity of proliferative
      diabetic retinopathy 3 months after panretinal photocoagulation.
AB  - BACKGROUND/AIMS: Proliferative diabetic retinopathy (PDR) is a severe blinding
      condition. We investigated whether retinal metabolism, measured by retinal
      oximetry, may predict PDR activity after panretinal laser photocoagulation (PRP).
      METHODS: We performed a prospective, interventional, clinical study of patients
      with treatment-naive PDR. Wide-field fluorescein angiography (OPTOS, Optomap) and
      global and focal retinal oximetry (Oxymap T1) were performed at baseline (BL),
      and 3 months (3M) after PRP. Angiographic findings were used to divide patients
      according to progression or non-progression of PDR after PRP. We evaluated
      differences in global and focal retinal oxygen saturation between patients with
      and without progression of PDR after PRP treatment. RESULTS: We included 45 eyes
      of 37 patients (median age and duration of diabetes were 51.6 and 20 years). Eyes
      with progression of PDR developed a higher retinal venous oxygen saturation than
      eyes with non-progression at 3M (global: +5.9% (95% CI -1.5 to 12.9), focal:
      +5.4%, (95% CI -4.1 to 14.8)). Likewise, progression of PDR was associated with a
      lower arteriovenular (AV) oxygen difference between BL and 3M (global: -6.1%,
      (95% CI -13.4 to -1.4), focal: -4.5% (95% CI -12.1 to 3.2)). In a multiple
      logistic regression model, increment in global retinal venular oxygen saturation
      (OR 1.30 per 1%-point increment, p=0.017) and decrement in AV oxygen saturation
      difference (OR 0.72 per 1%-point increment, p=0.016) at 3M independently
      predicted progression of PDR. CONCLUSION: Development of higher retinal venular
      and lower AV global oxygen saturation independently predicts progression of PDR
      despite standard PRP and might be a potential non-invasive marker of angiogenic
      disease activity.

PMID- 28765149
TI  - Changes in multiple cytokine concentrations in the aqueous humour of neovascular
      age-related macular degeneration after 2 months of ranibizumab therapy.
AB  - PURPOSE: To determine changes in multiple cytokine concentrations in the anterior
      chamber during the induction phase of ranibizumab treatment in patients with
      neovascular age-related macular degeneration (AMD). METHODS: This prospective
      study included 48 treatment-naive neovascular AMD eyes of 48 patients who
      received three consecutive monthly injections of ranibizumab at the Japan
      Community Health Care Organization Tokyo Shinjuku Medical Center between November
      2010 and August 2012. We collected ~0.2 mL aqueous humour before the first and
      third (2 months later) injections. Controls were 80 eyes with cataracts without
      retinal disease. The cytokines C-X-C motif chemokine ligand 1 (CXCL1), interferon
      gamma-induced protein 10 (IP-10), C-X-C motif chemokine ligand 12 (CXCL12), C-X-C
      motif chemokine ligand 13 (CXCL13), monocyte chemoattractant protein 1 (MCP-1),
      CCL11, C-C motif chemokine ligand 11 (CCL11), interleukin-6 (IL-6), interleukin
      10 (IL-10) and matrix metalloproteinase 9 (MMP-9) were analysed using multiplex
      cytokine assays. RESULTS: Mean ages of the patients with AMD and controls were 73
      and 75 years, respectively, and 31 (65%) and 37 (46%) subjects were men,
      respectively. Polypoidal choroidal vasculopathy was found in 27 eyes (56%). Mean
      concentrations of cytokines in aqueous humour in patients with neovascular AMD
      before the first and third ranibizumab injections were as follows (in pg/mL):
      CXCL1, 8.4 and 3.3; IP-10, 110 and 55; CXCL12, 480 and 240; CXCL13, 9.2 and 2.6;
      MCP-1, 620 and 220; CCL11, 7.1 and 2.8; IL-6, 5.9 and 1.6; IL-10, 0.15 and 0.015
      (all p<0.0001), and MMP-9, 0.92 and 1.5 (p=0.0216), respectively. Concentrations
      of all cytokines decreased significantly after two consecutive ranibizumab
      injections, except for MMP-9, which increased significantly. CONCLUSIONS: After
      two monthly consecutive antivascular endothelial growth factor injections,
      inflammatory cytokine levels in the aqueous humour of the eyes with AMD were
      strongly suppressed, while MMP-9 levels increased.

PMID- 28765151
TI  - Isolated Fourth Heart Sound.

PMID- 28765150
TI  - Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With
      Normal Kidney Function.
AB  - BACKGROUND: Heart failure (HF) is associated with poor cardiac outcomes and
      mortality. It is not known whether HF leads to poor renal outcomes in patients
      with normal kidney function. We hypothesized that HF is associated with worse
      long-term renal outcomes. METHODS AND RESULTS: Among 3 570 865 US veterans with
      estimated glomerular filtration rate (eGFR) >=60 mL min-1 1.73 m-2 during October
      1, 2004 to September 30, 2006, we identified 156 743 with an International
      Classification of Diseases, Ninth Revision, diagnosis of HF. We examined the
      association of HF with incident chronic kidney disease (CKD), the composite of
      incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5
      mL min-1 1.73 m-2 y-1) using Cox proportional hazard analyses and logistic
      regression. Adjustments were made for various confounders. The mean+/-standard
      deviation baseline age and eGFR of HF patients were 68+/-11 years and 78+/-14 mL
      min-1 1.73 m-2 and in patients without HF were 59+/-14 years and 84+/-16 mL min-1
      1.73 m-2, respectively. HF patients had higher prevalence of hypertension,
      diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases,
      stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients
      versus 14.5/1000 patient-years in patients without HF, and 22% of patients with
      HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF
      patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of
      incident CKD, composite of CKD or mortality, and rapid eGFR decline,
      respectively. CONCLUSIONS: HF is associated with significantly higher risk of
      incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis
      and management of HF could help reduce the risk of long-term renal complications.

PMID- 28765152
TI  - Erratum for Quiros et al., "Improving Detection of Shiga Toxin-Producing
      Escherichia coli by Molecular Methods by Reducing the Interference of Free Shiga
      Toxin-Encoding Bacteriophages".

PMID- 28765153
TI  - Erratum for Martinez-Castillo et al., "Shiga Toxin 2-Encoding Bacteriophages in
      Human Fecal Samples from Healthy Individuals".

PMID- 28765154
TI  - Gemcitabine-Induced TIMP1 Attenuates Therapy Response and Promotes Tumor Growth
      and Liver Metastasis in Pancreatic Cancer.
AB  - Gemcitabine constitutes one of the backbones for chemotherapy treatment in
      pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to
      this agent. Molecular markers downstream of gemcitabine treatment in preclinical
      models may provide an insight into resistance mechanisms. Using cytokine arrays,
      we identified potential secretory biomarkers of gemcitabine resistance (response)
      in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We
      verified the oncogenic role of the cytokine tissue inhibitor of matrix
      metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using
      both in vitro techniques and animal models. We identified potential pathways
      affected downstream of TIMP1 using the Illumina Human H12 array. Our findings
      were validated in both primary and metastatic models of pancreatic cancer.
      Gemcitabine increased inflammatory cytokines including TIMP1 in the KPC mouse
      model. TIMP1 was upregulated in patients with pancreatic intraepithelial
      neoplasias grade 3 and PDAC lesions relative to matched normal pancreatic tissue.
      In addition, TIMP1 played a role in tumor clonogenic survival and vascular
      density, while TIMP1 inhibition resensitized tumors to gemcitabine and
      radiotherapy. We observed a linear relationship between TIMP-1 expression, liver
      metastatic burden, and infiltration by CD11b+Gr1+ myeloid cells and
      CD4+CD25+FOXP3+ Tregs, whereas the presence of tumor cells was required for
      immune cell infiltration. Overall, our results identify TIMP1 upregulation as a
      resistance mechanism to gemcitabine and provide a rationale for combining
      chemo/radiotherapy with TIMP1 inhibitors in PDAC. Cancer Res; 77(21); 5952-62.
      (c)2017 AACR.

PMID- 28765156
TI  - Family Planning in the Context of Latin America's Universal Health Coverage
      Agenda.
AB  - BACKGROUND: Countries in Latin America and the Caribbean (LAC) have substantially
      improved access to family planning over the past 50 years. Many have also
      recently adopted explicit declarations of universal rights to health and
      universal health coverage (UHC) and have begun implementing UHC-oriented health
      financing schemes. These schemes will have important implications for the
      sustainability and further growth of family planning programs throughout the
      region. METHODS: We examined the status of contraceptive methods in major health
      delivery and financing schemes in 9 LAC countries. Using a set of 37 indicators
      on family planning coverage, family planning financing, health financing, and
      family planning inclusion in UHC-oriented schemes, we conducted a desk review of
      secondary sources, including population surveys, health financing assessments,
      insurance enrollment reports, and unit cost estimates, and interviewed in-country
      experts.Findings: Although the modern contraceptive prevalence rate (mCPR) has
      continued to increase in the majority of LAC countries, substantial disparities
      in access for marginalized groups remain. On average, mCPR is 20% lower among
      indigenous women than the general population, 5% lower among uninsured women than
      insured, and 7% lower among the poorest women than the wealthiest. Among the
      poorest quintile of women, insured women had an mCPR 16.5 percentage points
      higher than that of uninsured women, suggesting that expansion of insurance
      coverage is associated with increased family planning access and use. In the high
      and upper-middle-income countries we reviewed, all modern contraceptive methods
      are typically available through the social health insurance schemes that cover a
      majority of the population. However, in low- and lower-middle-income countries,
      despite free provision of most family planning services in public health
      facilities, stock-outs and implicit rationing present substantial barriers that
      prevent clients from accessing their preferred method or force them to pay out of
      pocket. CONCLUSION: Leveraging UHC-oriented schemes to sustain and further
      increase family planning progress will require that governments take deliberate
      steps to (1) target poor and informal sector populations, (2) include family
      planning in benefits packages, (3) ensure sufficient financing for family
      planning, and (4) reduce nonfinancial barriers to access. Through these steps,
      countries can increase financial protection for family planning and better ensure
      the right to health of poor and marginalized populations.

PMID- 28765155
TI  - Mitochondrial Superoxide Increases Age-Associated Susceptibility of Human Dermal
      Fibroblasts to Radiation and Chemotherapy.
AB  - Elderly cancer patients treated with ionizing radiation (IR) or chemotherapy
      experience more frequent and greater normal tissue toxicity relative to younger
      patients. The current study demonstrates that exponentially growing fibroblasts
      from elderly (old) male donor subjects (70, 72, and 78 years) are significantly
      more sensitive to clonogenic killing mediated by platinum-based chemotherapy and
      IR (~70%-80% killing) relative to young fibroblasts (5 months and 1 year; ~10%
      20% killing) and adult fibroblasts (20 years old; ~10%-30% killing). Old
      fibroblasts also displayed significantly increased (2-4-fold) steady-state levels
      of O2*-, O2 consumption, and mitochondrial membrane potential as well as
      significantly decreased (40%-50%) electron transport chain (ETC) complex I, II,
      IV, V, and aconitase (70%) activities, decreased ATP levels, and significantly
      altered mitochondrial structure. Following adenoviral-mediated overexpression of
      SOD2 activity (5-7-fold), mitochondrial ETC activity and aconitase activity were
      restored, demonstrating a role for mitochondrial O2*- in these effects. Old
      fibroblasts also demonstrated elevated levels of endogenous DNA damage that were
      increased following treatment with IR and chemotherapy. Most importantly,
      treatment with the small-molecule, superoxide dismutase mimetic (GC4419; 0.25
      MUmol/L) significantly mitigated the increased sensitivity of old fibroblasts to
      IR and chemotherapy and partially restored mitochondrial function without
      affecting IR or chemotherapy-induced cancer cell killing. These results support
      the hypothesis that age-associated increased O2*- and resulting DNA damage
      mediate the increased susceptibility of old fibroblasts to IR and chemotherapy
      that can be mitigated by GC4419. Cancer Res; 77(18); 5054-67. (c)2017 AACR.

PMID- 28765157
TI  - Ciliary Motility: Regulation of Axonemal Dynein Motors.
AB  - Ciliary motility is crucial for the development and health of many organisms.
      Motility depends on the coordinated activity of multiple dynein motors arranged
      in a precise pattern on the outer doublet microtubules. Although significant
      progress has been made in elucidating the composition and organization of the
      dyneins, a comprehensive understanding of dynein regulation is lacking. Here, we
      focus on two conserved signaling complexes located at the base of the radial
      spokes. These include the I1/f inner dynein arm associated with radial spoke 1
      and the calmodulin- and spoke-associated complex and the nexin-dynein regulatory
      complex associated with radial spoke 2. Current research is focused on
      understanding how these two axonemal hubs coordinate and regulate the dynein
      motors and ciliary motility.

PMID- 28765158
TI  - Erratum: Functional Prions in the Brain.

PMID- 28765159
TI  - The power of the few.
AB  - Converging evidence from numerous laboratories has revealed that malignant brain
      cancers are complex ecological systems composed of distinct cellular and
      acellular elements that collectively dictate glioblastoma biology. Our
      understanding of the individual contributions of each of these components is
      vital to the design of effective therapies against these cancers. In this issue
      of Genes & Development, Zanca and colleagues (pp. 1212-1227) demonstrate that one
      subpopulation of glioblastoma cells expressing a mutant epidermal growth factor
      receptor (EGFRvIII) is responsible for the survival of non-EGFRvIII-expressing
      tumor cells as well as for evading molecularly targeted therapy.

PMID- 28765162
TI  - Five minutes with . . . Neena Modi.

PMID- 28765161
TI  - The interplay between epigenetic changes and the p53 protein in stem cells.
AB  - Epigenetic programs regulate the development and maintenance of organisms over a
      lifetime. These programs are carried out through chemical modifications of DNA
      and proteins such as histones and transcription factors. These epigenetic
      modifications are less stable than genetic alterations and even reversible under
      a variety of circumstances, such as developmental changes, regeneration of
      tissues, cell divisions, aging, and pathological conditions observed in many
      cancers. The p53 protein not only enforces the stability of the genome by the
      prevention of genetic alterations in cells but also plays a role in regulating
      the epigenetic changes that can occur in cells. The full-length p53 protein is
      largely inactive in stem cells but, when activated, helps to commit these cells
      to developmental lineages through a series of epigenetic changes. Just as p53
      impacts epigenetic change, the enzyme activities that carry out epigenetic
      protein modifications act on the p53 protein and its splice variants in stem and
      progenitor cells to silence or activate its transcriptional activities. Thus,
      there is a great deal of cross-talk between the p53 protein and epigenetic
      programs. This review collects the diverse experimental evidence that leads to
      these conclusions. This in turn permits new ideas and directions for the
      treatment of cancers, reactivating developmental pathways for tissue regeneration
      and responses to the impact of aging.

PMID- 28765160
TI  - Genome integrity and disease prevention in the nervous system.
AB  - Multiple DNA repair pathways maintain genome stability and ensure that DNA
      remains essentially unchanged over the life of a cell. Various human diseases
      occur if DNA repair is compromised, and most of these impact the nervous system,
      in some cases exclusively. However, it is often unclear what specific endogenous
      damage underpins disease pathology. Generally, the types of causative DNA damage
      are associated with replication, transcription, or oxidative metabolism; other
      direct sources of endogenous lesions may arise from aberrant topoisomerase
      activity or ribonucleotide incorporation into DNA. This review focuses on the
      etiology of DNA damage in the nervous system and the genome stability pathways
      that prevent human neurologic disease.

PMID- 28765163
TI  - Epigenome profiling and editing of neocortical progenitor cells during
      development.
AB  - The generation of neocortical neurons from neural progenitor cells (NPCs) is
      primarily controlled by transcription factors binding to DNA in the context of
      chromatin. To understand the complex layer of regulation that orchestrates
      different NPC types from the same DNA sequence, epigenome maps with cell type
      resolution are required. Here, we present genomewide histone methylation maps for
      distinct neural cell populations in the developing mouse neocortex. Using
      different chromatin features, we identify potential novel regulators of cortical
      NPCs. Moreover, we identify extensive H3K27me3 changes between NPC subtypes
      coinciding with major developmental and cell biological transitions.
      Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial
      transcription factors, including the basal progenitor regulator Eomes We use
      catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit
      H3K27me3 at the Eomes locus in vivo, which results in reduced Tbr2 expression and
      lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3
      changes during neocortex development. Taken together, we provide a rich resource
      of neocortical histone methylation data and outline an approach to investigate
      its contribution to the regulation of selected genes during neocortical
      development.

PMID- 28765164
TI  - Selective termination of lncRNA transcription promotes heterochromatin silencing
      and cell differentiation.
AB  - Long non-coding RNAs (lncRNAs) regulating gene expression at the chromatin level
      are widespread among eukaryotes. However, their functions and the mechanisms by
      which they act are not fully understood. Here, we identify new fission yeast
      regulatory lncRNAs that are targeted, at their site of transcription, by the YTH
      domain of the RNA-binding protein Mmi1 and degraded by the nuclear exosome. We
      uncover that one of them, nam1, regulates entry into sexual differentiation.
      Importantly, we demonstrate that Mmi1 binding to this lncRNA not only triggers
      its degradation but also mediates its transcription termination, thus preventing
      lncRNA transcription from invading and repressing the downstream gene encoding a
      mitogen-activated protein kinase kinase kinase (MAPKKK) essential to sexual
      differentiation. In addition, we show that Mmi1-mediated termination of lncRNA
      transcription also takes place at pericentromeric regions where it contributes to
      heterochromatin gene silencing together with RNA interference (RNAi). These
      findings reveal an important role for selective termination of lncRNA
      transcription in both euchromatic and heterochromatic lncRNA-based gene silencing
      processes.

PMID- 28765165
TI  - The Relationship Between Body Composition and Bone Quality Measured with HR-pQCT
      in Peritoneal Dialysis Patients.
AB  - BACKGROUND: Bone is known to be impaired in chronic kidney disease and dialysis
      patients. Recent studies have shown that body composition (fat mass and lean
      mass) may impact bone health. Some of these effects may be related to mediators
      that are secreted by adipose tissue. METHODS: The aim of this study was to
      evaluate the association between body composition (dual x-ray absorptiometry
      [DEXA]) and adipokines (leptin, adiponectin), with bone density and
      microarchitecture assessed with high-resolution peripheral quantitative computed
      tomography (HR-pQCT) in chronic peritoneal dialysis (PD) patients in a single
      center prospective study. RESULTS: Twenty-three patients with a median age of 61
      years and body mass index (BMI) of 27 kg/m2 were recruited. On univariate
      analysis, age was negatively associated with total volumetric bone mineral
      density (vBMD) (r = -0.75, p < 0.01), cortical vBMD (r = -0.85, p < 0.01), and
      cortical thickness (r = -0.71, p < 0.01). There was a negative association
      between leptin and cortical thickness (r = -0.48, p = 0.021). Fat mass (FM) was
      negatively correlated with cortical thickness (r = -0.52, p = 0.012). No
      association was found between bone parameters and dialysis duration, serum
      insulin, intact parathyroid hormone, osteocalcin, and adiponectin. The short
      dialysis vintage could in part explain the lack of correlation with bone
      parameters. In multivariate analysis, FM was significantly and negatively
      correlated with total vBMD, cortical and trabecular thickness. CONCLUSIONS: These
      data suggest that FM is negatively associated with bone quality in PD patients,
      supporting a relation between body composition and bone that is independent from
      other dialysis-associated complications. The relative contribution of the
      different fat deposits (visceral versus subcutaneous) needs to be assessed in
      future studies.

PMID- 28765166
TI  - Impact of the Karnofsky Performance Status on Survival and its Dynamics During
      the Terminal Year of Peritoneal Dialysis Patients.
AB  - BACKGROUND: Simple and low-cost tools to monitor the risk profile of patients on
      peritoneal dialysis (PD) at high risk of complications and mortality are scarce.
      One of the tools available to monitor the variation in vitality and dependence
      levels is the Karnofsky performance status (KPS). This study analyzed the average
      trends and variation of KPS during the 12 months before death and its independent
      value in predicting patients' survival. METHODS: The data were compiled from the
      BRAZPD II multicenter study, performed in Brazil between 2004 and 2011. For the
      analysis of KPS dynamics, we included patients with at least 12 months of follow
      up on PD and who had a fatal event during the follow-up. The following
      covariables were evaluated: age, gender, ethnicity, educational level, and
      presence of diabetes. We used the linear regression model to present the results:
      the log (time) before death was represented by the regression variable and KPS
      was the response. We also analyzed the independent impact of baseline KPS on
      patients' survival. RESULTS: From the population of 9,905 patients enrolled in
      the BRAZPD study, 4,133 survived 12 months on PD and were included in the
      analysis. There was a gradual decline in the KPS scores, which accelerated in the
      last 2 months before death. These changes were similar irrespective of age, race,
      family income, gender, diabetes, PD modality, and education level. We observed
      989 fatal events in this population during the observation period, and the KPS
      score was identified as an independent predictor for mortality in this cohort.
      CONCLUSIONS: This study demonstrates for the first time the dynamics of KPS
      before death in PD patients, indicating a progressive and accelerated decline of
      KPS in the 12 months before patients died. In addition, KPS was an independent
      predictor of mortality in this population.

PMID- 28765168
TI  - What's in a Name?

PMID- 28765167
TI  - Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD): Study Protocol
      for Establishing a Core Outcome Set in PD.
AB  - BACKGROUND: Worldwide, approximately 11% of patients on dialysis receive
      peritoneal dialysis (PD). Whilst PD may offer more autonomy to patients compared
      with hemodialysis, patient and caregiver burnout, technique failure, and
      peritonitis remain major challenges to the success of PD. Improvements in care
      and outcomes are likely to be mediated by randomized trials of innovative
      therapies, but will be limited if the outcomes measured and reported are not
      important for patients and clinicians. The aim of the Standardised Outcomes in
      Nephrology-Peritoneal Dialysis (SONG-PD) study is to establish a set of core
      outcomes for trials in patients on PD based on the shared priorities of all
      stakeholders, so that outcomes of most relevance for decision-making can be
      evaluated, and that interventions can be compared reliably. METHODS: The 5 phases
      in the SONG-PD project are: a systematic review to identify outcomes and outcome
      measures that have been reported in randomized trials involving patients on PD;
      focus groups using nominal group technique with patients and caregivers to
      identify, rank, and describe reasons for their choice of outcomes; semi
      structured key informant interviews with health professionals; a 3-round
      international Delphi survey involving a multi-stakeholder panel; and a consensus
      workshop to review and endorse the proposed set of core outcome domains for PD
      trials. DISCUSSION: The establishment of 3 to 5 high-priority core outcomes, to
      be measured and reported consistently in all trials in PD, will enable patients
      and clinicians to make informed decisions about the relative effectiveness of
      interventions, based upon outcomes of common importance.

PMID- 28765169
TI  - Categorizing biomedical research: the basics of translation.
AB  - As biomedical research has evolved over the past century, the terminology
      employed to categorize it has failed to evolve in parallel to accommodate the
      implications of these changes. In particular, the terms basic research and
      translational research as used today in biomedicine seem especially problematic.
      Here we review the origins of these terms, analyze some of the conceptual
      confusions attendant to their current use, and assess some of the deleterious
      consequences of these confusions. We summarize that the distinction between basic
      and translational biomedical research is an anachronism. Elimination of this
      often contentious distinction would improve both the culture and the
      effectiveness of the scientific process, and its potential benefits to society.
      Flier, J. S., Loscalzo, J. Categorizing biomedical research: the basics of
      translation.

PMID- 28765170
TI  - Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and
      signposts.
AB  - Support for the concept that herpes simplex virus type 1 (HSV1), when present in
      the brains of apolipoprotein E-epsilon4 carriers, is a major risk for Alzheimer's
      disease (AD) is increasing steadily, with over 120 publications providing direct
      or indirect evidence relevant to the hypothesis. No articles have contested the
      concept, apart from 3 published 13-18 yr ago. This review describes very recent
      studies on the role of HSV1 but refers also to older studies that provide
      background for some lesser-known related topics not covered in other recent
      reviews; these include the relevance of herpes simplex encephalitis and of
      epilepsy to AD, the action of IFN, and the possible relevance of the different
      types of DNA damage to AD-in particular, those caused by HSV1-and mechanisms of
      repair of damage. New epidemiologic data supporting previous studies on mild
      cognitive impairment and progression to AD are reviewed, as are those examining
      the relationship between total infectious burden (additive seropositivity to
      various microbes) and cognition/AD. The latter indicates the involvement of HSV1
      and cytomegalovirus (and the necessity of taking into account any marked
      differences in sensitivity of antibody detection). Recent studies that provide
      further support for the occurrence of repeated reactivation of latent HSV1 in the
      brain in AD pathogenesis are also discussed.-Itzhaki, R. F. Herpes simplex virus
      type 1 and Alzheimer's disease: possible mechanisms and signposts.

PMID- 28765171
TI  - Erratum.

PMID- 28765172
TI  - Leishmania donovani inhibits inflammasome-dependent macrophage activation by
      exploiting the negative regulatory proteins A20 and UCP2.
AB  - In visceral leishmaniasis, we found that the antileishmanial drug Amp B produces
      a higher level of IL-1beta over the infected control. Moreover, administering
      anti-IL-1beta antibody to infected Amp B-treated mice showed significantly less
      parasite clearance. Investigation revealed that Leishmania inhibits stimuli
      induced expression of a multiprotein signaling platform, NLRP3 inflammasome,
      which in turn inhibits caspase-1 activation mediated maturation of IL-1beta from
      its pro form. Attenuation of NLRP3 and pro-IL-1beta in infection was found to
      result from decreased NF-kappaB activity. Transfecting infected cells with
      constitutively active NF-kappaB plasmid increased NLRP3 and pro-IL-1beta
      expression but did not increase mature IL-1beta, suggesting that IL-1beta
      maturation requires a second signal, which was found to be reactive oxygen
      species (ROS). Decreased NF-kappaB was attributed to increased expression of A20,
      a negative regulator of NF-kappaB signaling. Silencing A20 in infected cells
      restored NLRP3 and pro-IL-1beta expression, but also increased matured IL-1beta,
      implying an NF-kappaB-independent A20-modulated IL-1beta maturation. Macrophage
      ROS is primarily regulated by mitochondrial uncoupling protein 2 (UCP2), and UCP2
      silenced infected cells showed an increased IL-1beta level. Short hairpin RNA
      mediated knockdown of A20 and UCP2 in infected mice independently documented
      decreased liver and spleen parasite burden and increased IL-1beta production.
      These results suggest that Leishmania exploits A20 and UCP2 to impair
      inflammasome activation for disease propagation.-Gupta, A. K., Ghosh, K., Palit,
      S., Barua, J., Das, P. K., Ukil, A. Leishmania donovani inhibits inflammasome
      dependent macrophage activation by exploiting the negative regulatory proteins
      A20 and UCP2.

PMID- 28765174
TI  - Role of telomeric repeat-containing RNA in telomeric chromatin remodeling during
      the early expansion of human embryonic stem cells.
AB  - This study aimed to explore the role of telomeric repeat-containing RNA (TERRA)
      in telomeric chromatin remodeling during the early expansion of human embryonic
      stem cells (hESCs). During the derivation of hESCs, histone demethylation in the
      telomeric region facilitates telomerase-mediated telomere elongation. An adequate
      telomere repeat is essential for hESCs to acquire and/or maintain the unlimited
      symmetric division, which suggests that there is a link between pluripotency and
      telomere maintenance. The present study found that the gradual decrease in TERRA
      levels and related TERRA foci were correlated with telomeric length elongation in
      the early expansion of hESCs. In addition, TERRA participated in telomeric
      chromatin remodeling by cooperating with SUV39H1 (suppressor of variegation 3-9
      homolog 1/2) to propagate telomeric heterochromatin marker, histone H3
      trimethylation of lysine 9. Moreover, the fibroblast growth factor signaling
      pathway, which is activated in hESCs, could suppress TERRA levels via telomeric
      repeat factor 1, which results in reduced SUV39H1 recruitment by TERRA at the
      telomere. Taken together, these results highlight the role of TERRA in hESC
      telomere elongation and homeostasis in the acquisition and/or maintenance of stem
      cell pluripotency.-Zeng, S., Liu, L., Sun, Y., Lu, G., Lin, G. Role of telomeric
      repeat-containing RNA in telomeric chromatin remodeling during the early
      expansion of human embryonic stem cells.

PMID- 28765173
TI  - A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced
      obesity.
AB  - Adenosine, a key extracellular signaling mediator, regulates several aspects of
      metabolism by activating 4 G-protein-coupled receptors, the A1, A2A, A2B, and A3
      adenosine receptors (ARs). The role of A2AARs in regulating high-fat-diet (HFD)
      induced metabolic derangements is unknown. To evaluate the role of A2AARs in
      regulating glucose and insulin homeostasis in obesity, we fed A2AAR-knockout (KO)
      and control mice an HFD for 16 wk to initiate HFD-induced metabolic disorder. We
      found that genetic deletion of A2AARs caused impaired glucose tolerance in mice
      fed an HFD. This impaired glucose tolerance was caused by a decrease in insulin
      secretion but not in insulin sensitivity. Islet size and insulin content in
      pancreata of A2AAR-deficient mice were decreased compared with control mice after
      consuming an HFD. A2AAR-KO mice had decreased expression of the beta-cell
      specific markers pdx1, glut2, mafA, and nkx6.1 and increased expression of the
      dedifferentiation markers sox2 and hes1. Ex vivo islet experiments confirmed the
      role of A2AARs in protecting against decreased insulin content and release caused
      by HFD. Other experiments with bone marrow chimeras revealed that inflammation
      was not the primary cause of decreased insulin secretion in A2AAR-KO mice.
      Altogether, our data showed that A2AARs control pancreatic dysfunction in HFD
      induced obesity.-Csoka, B., Toro, G., Vindeirinho, J., Varga, Z. V., Koscso, B.,
      Nemeth, Z. H., Kokai, E., Antonioli, L., Suleiman, M., Marchetti, P., Cseri, K.,
      Deak, A., Virag, L., Pacher, P., Bai, P., Hasko, G. A2A adenosine receptors
      control pancreatic dysfunction in high-fat-diet-induced obesity.

PMID- 28765176
TI  - Transient clinical improvement of a mitochondrial neurogastrointestinal
      encephalomyopathy-like syndrome after allogeneic haematopoietic stem cell
      transplantation.
AB  - Mitochondrial neurogastrointestinal encephalopathy (MNGIE), usually an autosomal
      recessive inherited condition, causes gastrointestinal dysmotility,
      ophthalmoplegia, ptosis, leukoencephalopathy and neuropathy. The chromosome 22
      disorder, due to mutations in the nuclear gene TYMP encoding thymidine
      phosphorylase (TP), leads to the accumulation of thymidine and deoxyuridine, with
      mitochondrial dysfunction.This report describes a patient with an MNGIE-like
      syndrome with a heterozygous TYMP mutation who showed marked, but transient
      improvement postallogeneic haematopoietic stem cell transplantation (HSCT).The
      patient, showing ptosis and ophthalmoplegia, was initially managed for myasthenia
      gravis. She developed gastrointestinal symptoms, dysarthria, dysphagia and
      weakness, and MNGIE was considered due to its low TP levels and improvement after
      platelet transfusions. She underwent HSCT, with dramatic improvement, but
      regressed 18 months later despite normal TP levels, platelet counts and full
      chimerism.MNGIE may encompass a spectrum of disorders. TP deficiency alone is
      unlikely to explain all clinical signs, and other factors, including the possible
      development of anti-TP antibodies, which may play a role in the pathophysiology.

PMID- 28765175
TI  - E-selectin-mediated rolling facilitates pancreatic cancer cell adhesion to
      hyaluronic acid.
AB  - Tumor cell extravasation is a multistep process preceded by cell rolling and
      arrest on the vessel wall via the formation of specific receptor-ligand bonds.
      The strength, availability, and number of receptor-ligand bonds regulate the rate
      by which tumor cells tether, roll, and adhere to vascular walls. Although the
      mechanics of selectin-mediated rolling have been extensively studied, little is
      known regarding how tumor cell rolling on selectins facilitates adhesion to a
      distinct substrate-bound protein with different kinetic properties. By using
      multicomponent protein patterning and a microfluidic system, we evaluated how E
      selectin-dependent rolling modulates hyaluronic acid (HA) adhesion as a function
      of fluid shear, contact time, and the spacing between E-selectin and HA regions
      patterned on the substrate. We show that tumor cells rolling on E-selectin were
      ~40-fold more likely to bind to HA than nonrolling cells in shear flow.
      Furthermore, E-selectin-dependent rolling promotes adhesion to HA by both
      physically slowing cells and enabling them to position proximal to the surface,
      thereby increasing the on rate of adhesion. A better understanding of tumor cell
      adhesion under physiologic shear would lead to the development of new diagnostic
      assays and pave the way to clinical approaches aimed ultimately to halt
      metastasis.-Shea, D. J., Li, Y. W., Stebe, K. J., Konstantopoulos, K. E-selectin
      mediated rolling facilitates pancreatic cancer cell adhesion to hyaluronic acid.

PMID- 28765177
TI  - Massive juvenile nasopharyngeal angiofibroma: ode to the open surgical approach.
AB  - The management of juvenile nasopharyngeal angiofibroma has undergone a
      significant evolution, with more surgeons moving towards the minimal invasive
      endoscopic approaches. Although considered the standard of care by most, an
      endoscopic approach may not be sufficient for extensive tumours, as exemplified
      by the current case of a young man presenting with the largest juvenile
      nasopharyngeal angiofibroma described in English literature until the present
      that was eventually excised via an anterior external approach.

PMID- 28765178
TI  - Stercoral perforation of the colon in a heroin addict.
AB  - A 27-year-old female heroin addict presented with a peritonitic and distended
      abdomen. Her medical history included depression and a 3-year history of heroin
      abuse with attendant constipation. CT scan showed free intraperitoneal gas,
      massive faecal distension of the rectum and sigmoid colon and likely bowel
      necrosis. She underwent an emergency Hartmann's procedure for perforation of the
      sigmoid colon. Pathology identified two areas of stercoral ulceration, one of
      them being the area of perforation. Postoperatively, the patient developed a deep
      vein thrombosis and is now on anticoagulant therapy. She was discharged 4 weeks
      after admission. The patient has been reviewed at follow-up clinic by the
      surgical team and specialist stoma nurses. She is coping well with good stoma
      function. We will perform a colonoscopy to identify any further areas of
      stercoral ulceration but there are no plans for further surgery at present.

PMID- 28765179
TI  - Status epilepticus as the initial presentation of antibody-negative Goodpasture's
      syndrome.
AB  - Goodpasture's syndrome is a rare pulmonary-renal disease. It is characterised by
      presence of auto-antibodies directed against the glomerular basement membrane
      (GBM) antigen. These antibodies that bind to the GBM antigens cause rapidly
      progressive glomerulonephritis. The alveolar basement membrane also contains
      similar antigen, leading to pulmonary haemorrhage in active disease. We report a
      case of a young man who initially presented with status epilepticus and later was
      found to have rapidly progressive glomerulonephritis with pulmonary haemorrhage.
      Serum anti-GBM antibody was negative but the renal biopsy confirmed the diagnosis
      by showing typical linear IgG along the GBM on immunofluorescent study. He was
      treated with plasmapheresis and high-dose steroid in combination with oral
      cyclophosphamide. His renal function normalised after treatment.

PMID- 28765180
TI  - Isolated third nerve palsy: a rare neurological presentation of Burkitt's
      lymphoma.
AB  - Lymphoma patient presenting with isolated third nerve palsy is relatively rare,
      and diagnosis of underlying disease may be challenging. Until this date, less
      than 20 cases have been described in the literature. This is the case of a 3-year
      old boy who presented to neurologist with ptosis of left eye for 8 days. On
      examination, abdominal mass was detected, and the child was referred to
      paediatric surgery department. Laparotomy and excision of the mass was done.
      Histopathology and immunohistochemistry of the mass confirmed it to be a case of
      Burkitt's lymphoma. At this point, the patient was referred to haematology
      department. Contrast-enhanced CT brain showed infiltration around left cavernous
      sinus. Patient was treated with two cycles of R-CODOX-M/R-IVAC. Ptosis improved
      completely within few days of starting chemotherapy. Follow-up positron emission
      tomography CT scan done after the second cycle of chemotherapy revealed no
      metabolically active disease.

PMID- 28765181
TI  - Rare presentation of bilobed posterior tongue in Goldenhar syndrome.
AB  - A bilobed posterior tongue is a rare malformation with few reported cases in the
      literature. This anomaly has not been demonstrated in patients with Goldenhar
      syndrome. We report a case of a 5-month-old child with the classic signs of
      Goldenhar syndrome and laryngomalacia with an incidental finding of a bilobed
      posterior tongue. Careful assessment and monitoring are crucial, especially in
      syndromic babies.

PMID- 28765182
TI  - A vulnerable plaque identified on CT coronary angiography: when should we act in
      stable coronary artery disease?
AB  - CT coronary angiography (CTCA) is increasingly being used to diagnose coronary
      artery disease (CAD). Recent technological advancements, including dual energy CT
      and improved gantry times, have led to the ability to image coronary arteries
      with excellent spatial resolution at low radiation doses. Atheromatous plaques
      can be identified using CTCA and assessed to establish the risk of acute coronary
      syndrome from each individual plaque. If CTCA identifies CAD, it should then be
      used in conjunction with functional testing or invasive angiography with
      physiological assessment to establish the significance of coronary disease in an
      individual patient. In this case, the patient was diagnosed with an acute
      coronary syndrome originating from an atheromatous plaque that had been
      identified on CTCA 15 months before the acute event. The patient had positive
      ischaemic testing on myocardial perfusion scan but no symptoms of angina prior to
      the acute event. This case highlights the increasing difficulties clinicians face
      when deciding on management for patients with high-risk plaques, as there are
      little guidelines beyond aggressive secondary prevention.

PMID- 28765183
TI  - A case of bronchiolitis obliterans organising pneumonia associated with SAPHO
      (synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome.
AB  - A 57-year-old woman with SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis)
      syndrome presented with recurrent episodes of pneumonia. She was treated with
      multiple courses of antibiotics with no success. The transbronchial biopsy
      undertaken via bronchoscopy revealed organising pneumonia (OP). She was treated
      with steroids and responded well with full clinical recovery and normalisation of
      her chest X-ray.To our knowledge, this is the first reported case of OP in
      association with SAPHO syndrome. This case report highlights the importance of
      considering OP in patients with SAPHO syndrome who present with chest infection.

PMID- 28765184
TI  - Environmental sensitivity as a trigger of erythema nodosum and perimenopausal
      symptoms.
AB  - A 45-year-old woman presented to the University of Arizona Integrative Medicine
      Clinic for advice on managing recurrent erythema nodosum (EN), along with recent
      onset perimenopausal symptoms. Her painful EN flares had occurred two to six
      times per year over the past 14 years, yet had attenuated over the past 5 years
      until recently, and she presented with bilateral EN lesions on the shins. An
      environmental exposure history revealed that a new plastic-containing water pot
      had been introduced at her office just prior to her latest EN flare. She was told
      to eliminate environmental exposure to plastics, including this new coffee pot.
      She eliminated exposures to heated plastics, and replaced her coffee pot with a
      stainless steel one. Within weeks of removing these potential environmental
      triggers, her EN lesions cleared completely, and her menses normalised. An
      unintentional re-exposure to plastics 2 months later resulted in an EN recurrence
      within 2 hours.

PMID- 28765185
TI  - A delayed presentation of ameloblastic fibrosarcoma in an African patient.
AB  - A 24-year-old womanpresented with ameloblastic fibrosarcoma arising from
      ameloblastic fibroma. The delayed presentation accounted for the extensive
      destruction of the mandible and complete occlusion of her oral cavity. This
      resulted in an inability to eat and maintain oral hygiene. A multidisciplinary
      team management approach involved nutritional optimisation, segmental
      mandibulectomy, reconstruction with a reconstructive plate and a free
      anterolateral thigh flap to line the the floor of mouth. Functional and aesthetic
      outcome was acceptable, and the patient is planned for secondary free fibular
      flap bony reconstruction.

PMID- 28765186
TI  - Tuberculous pericarditis treated with steroid in a dialysis patient.
AB  - Mycobacterium tuberculosis has spread worldwide and its mortality rate had been
      very high. The prevention technology and antituberculosis (TB) chemotherapy has
      improved its prognosis. However, immunocompromised patients, such as those who
      had HIV infection, older age and on haemodialysis, are still at high risk of TB
      infection. TB pericarditis is a common cause of constrictive pericarditis and its
      mortality remains high. Early diagnosis and initiation of appropriate therapy are
      critical to improve mortality. Additionally, detection of an elevation in the
      adenosine deaminase level in pericardial effusion is reported to be useful. We
      report the case of an immunocompromised patient with TB pericarditis, and steroid
      therapy could prevent him from progressing to constrictive pericarditis. The
      adenosine deaminase value of pericardial effusion was so helpful that we could
      promptly make clinical and therapeutic decisions.

PMID- 28765187
TI  - Non-atherosclerotic aortic mural thrombus: a rare source of embolism.
AB  - A 54-year-old man presented to the emergency department with acute left-sided
      chest pain and left upper quadrant abdominal pain. He had a significant history
      of squamous cell carcinoma of the lung previously treated with right
      pneumonectomy who ; is currently receiving adjuvant chemotherapy with cisplatin.
      Physical examination was remarkable for tachycardia, hypertension and mild
      abdominal tenderness. CT angiography revealed an aortic mural thrombus in the
      ascending aorta and aortic arch without dissection, aneurysm or tortuosity of the
      aorta. In addition, an infarction of the inferior spleen was reported. Given the
      high risk of surgery for this patient, he was treated conservatively with esmolol
      and heparin infusion. His subsequent hospital course was uneventful, and he was
      successfully discharged on enoxaparin therapy that was successively bridged to
      rivaroxaban treatment. Follow-up transesophageal echocardiography and CT
      angiography at one month showed no thrombus in the aorta.

PMID- 28765188
TI  - Vanishing metatarsal: a rare manifestation of primary hyperparathyroidism.

PMID- 28765189
TI  - Expanding the differential: toluene-induced toxicity.
AB  - A 31-year-old woman presented to the hospital with generalised weakness and lower
      back and abdominal pain. The only significant finding on physical examination was
      the weakness of the legs. Laboratory analysis in the emergency department
      revealed that she was hypokalaemic with metabolic acidosis. She was treated with
      oral and intravenous potassium, which resolved her weakness. During the search
      for an explanation for her renal tubular acidosis, she said she was exposed to
      paint exposure while working on a friend's house. She was discharged on
      correction of her hypokalaemia, and a subsequent test revealed elevated blood
      toluene level.

PMID- 28765190
TI  - Reversible central neural hyperexcitability: an electroencephalographic clue to
      hypocalcaemia.
AB  - A 23-year-old male patient presented with cognitive decline and seizures.
      Examination revealed Chvostek's and Trousseau's signs. Investigations revealed
      hypocalcaemia, hyperphosphatemia and normal intact parathyroid hormone levels.
      Imaging showed calcifications in bilateral basal ganglia, thalamus and dentate
      nuclei. Interictal electroencephalogram showed theta range slowing of background
      activity and bilateral temporo-occipital, irregular, sharp and slow wave
      discharges, which accentuated during hyperventilation, photic stimulation and eye
      closure. Appearance of epileptiform discharges after eye closure,
      hyperventilation and photic stimulation may suggest presence of central neural
      hyperexcitability due to hypocalcaemia. These features may be an equivalent of
      peripheral neuromuscular hyperexcitability (Chvostek's and Trousseau's signs)
      that occurs in hypocalcaemia. The clinical and electroencephalographic features
      completely reversed with correction of serum calcium without antiepileptic
      medications. It is important for clinicians to recognise these reversible
      changes, as it can help to avoid misdiagnosis and long-term administration of
      antiepileptic becomes unnecessary.

PMID- 28765191
TI  - Flowing back and forth: a coronary malformation.

PMID- 28765192
TI  - Four-dimensional CT-guided transcatheter removal of a fractured migrated catheter
      of a totally implantable venous access port.
AB  - Patients undergoing chemotherapy usually undergo placement of a totally
      implantable venous access port (TIVAP), but TIVAP catheter fracture is rare. We
      encountered a case where flushing the TIVAP catheter became impossible because of
      resistance. A 61-year-old-woman underwent TIVAP placement. Although a chest X-ray
      revealed the fractured catheter had migrated into the right hilar area, the
      timing of the fracture was unclear. Four-dimensional computed tomography (4D-CT)
      showed that the tip of the fractured catheter was located at the anterior
      segmental artery of the right upper lobe and was immobile, with the remaining
      portion flapping with the blood flow. Transcatheter removal of the migrated
      catheter was judged to be possible and was performed successfully. 4D-CT may be
      useful as an appropriate approach in transcatheter removal of a migrated
      fractured catheter.

PMID- 28765193
TI  - Gottron papule-like skin changes.

PMID- 28765194
TI  - Effect of Green Tea Supplements on Liver Enzyme Elevation: Results from a
      Randomized Intervention Study in the United States.
AB  - Liver injury effects of green tea-based products have been reported in sporadic
      case reports. However, no study has examined systematically such adverse effects
      in an unbiased manner. We examined the potential effects of a high, sustained
      oral dose of green tea extract (GTE) on liver injury measures in a randomized,
      placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075
      women with the original aim to assess the effect of daily GTE consumption for 12
      months on biomarkers of breast cancer risk. The current analysis examined the
      effect of GTE consumption on liver injury in 1,021 participants (513 in GTE and
      508 in placebo arm) with normal baseline levels of liver enzymes. Among women in
      the GTE arm, alanine aminotransferase (ALT) increased by 5.4 U/L [95% confidence
      interval (CI), 3.6-7.1] and aspartate aminotransferase increased by 3.8 U/L (95%
      CI, 2.5-5.1), which were significantly higher than those among women in the
      placebo arm (both P < 0.001). Overall, 26 (5.1%) women in GTE developed moderate
      or more severe abnormalities in any liver function measure during the
      intervention period, yielding an OR of 7.0 (95% CI, 2.4-20.3) for developing
      liver function abnormalities as compared with those in the placebo arm. ALT
      returned to normal after dechallenge and increased again after one or more
      rechallenges with GTE. The rise-fall pattern of liver enzyme values following the
      challenge-dechallenge cycles of GTE consumption strongly implicates the effect of
      high-dose GTE on liver enzyme elevations. Cancer Prev Res; 10(10); 571-9. (c)2017
      AACR.

PMID- 28765195
TI  - Prospective Evaluation of Multimodal Optical Imaging with Automated Image
      Analysis to Detect Oral Neoplasia In Vivo.
AB  - The 5-year survival rate for patients with oral cancer remains low, in part
      because diagnosis often occurs at a late stage. Early and accurate identification
      of oral high-grade dysplasia and cancer can help improve patient outcomes.
      Multimodal optical imaging is an adjunctive diagnostic technique in which
      autofluorescence imaging is used to identify high-risk regions within the oral
      cavity, followed by high-resolution microendoscopy to confirm or rule out the
      presence of neoplasia. Multimodal optical images were obtained from 206 sites in
      100 patients. Histologic diagnosis, either from a punch biopsy or an excised
      surgical specimen, was used as the gold standard for all sites. Histopathologic
      diagnoses of moderate dysplasia or worse were considered neoplastic. Images from
      92 sites in the first 30 patients were used as a training set to develop
      automated image analysis methods for identification of neoplasia. Diagnostic
      performance was evaluated prospectively using images from 114 sites in the
      remaining 70 patients as a test set. In the training set, multimodal optical
      imaging with automated image analysis correctly classified 95% of nonneoplastic
      sites and 94% of neoplastic sites. Among the 56 sites in the test set that were
      biopsied, multimodal optical imaging correctly classified 100% of nonneoplastic
      sites and 85% of neoplastic sites. Among the 58 sites in the test set that
      corresponded to a surgical specimen, multimodal imaging correctly classified 100%
      of nonneoplastic sites and 61% of neoplastic sites. These findings support the
      potential of multimodal optical imaging to aid in the early detection of oral
      cancer. Cancer Prev Res; 10(10); 563-70. (c)2017 AACR.

PMID- 28765197
TI  - Nutritional Considerations in Pediatric Chronic Disease.

PMID- 28765198
TI  - The Pediatrician's Role in Encouraging Exclusive Breastfeeding.

PMID- 28765196
TI  - In Silico Systems Biology Analysis of Variants of Uncertain Significance in Lynch
      Syndrome Supports the Prioritization of Functional Molecular Validation.
AB  - Lynch syndrome (LS) is a genetic condition secondary to germline alterations in
      the DNA mismatch repair (MMR) genes with 30% of changes being variants of
      uncertain significance (VUS). Our aim was to perform an in silico
      reclassification of VUS from a large single institutional cohort that will help
      prioritizing functional validation. A total of 54 VUS were detected with 33 (61%)
      novel variants. We integrated family history, pathology, and genetic information
      along with supporting evidence from eight different in silico tools at the RNA
      and protein level. Our assessment allowed us to reclassify 54% (29/54) of the VUS
      as probably damaging, 13% (7/54) as possibly damaging, and 28% (15/54) as
      probably neutral. There are more than 1,000 VUS reported in MMR genes and our
      approach facilitates the prioritization of further functional efforts to assess
      the pathogenicity to those classified as probably damaging. Cancer Prev Res;
      10(10); 580-7. (c)2017 AACR.

PMID- 28765199
TI  - Hypertension in Children and Adolescents.

PMID- 28765200
TI  - Case 1: Progressive Hypotonia and Decreased Alertness in an 8-month-old Girl.

PMID- 28765201
TI  - Case 2: New-onset Seizures in a 14-year-old Boy.

PMID- 28765202
TI  - Case 3: Painless Vision Loss in an Adolescent.

PMID- 28765203
TI  - Case 4: Ear Pain and Weight Loss in a 13-year-old Boy.

PMID- 28765204
TI  - Case 5: Chest Pain and Elevated Troponin in a Teenager.

PMID- 28765205
TI  - Case 6: Skin Discoloration, Methemoglobinemia, and Acute Interstitial Nephritis
      in a 15-year-old Girl.

PMID- 28765206
TI  - Peanuts and LEAP Data.

PMID- 28765207
TI  - Visual Diagnosis: A Neonate with Rash and Fever.

PMID- 28765209
TI  - Deep implant insertions and ethyl chloride.

PMID- 28765208
TI  - Plasma cholesterol level determines in vivo prion propagation.
AB  - Transmissible spongiform encephalopathies are fatal neurodegenerative diseases
      with an urgent need for therapeutic and prophylactic strategies. At the time when
      the blood-mediated transmission of prions was demonstrated, in vitro studies
      indicated a high binding affinity of the scrapie prion protein (PrPSc) with apoB
      containing lipoproteins, i.e., the main carriers of cholesterol in human blood.
      The aim of the present study was to explore the relationship between circulating
      cholesterol-containing lipoproteins and the pathogenicity of prions in vivo. We
      showed that, in mice with a genetically engineered deficiency for the plasma
      lipid transporter, phospholipid transfer protein (PLTP), abnormally low
      circulating cholesterol concentrations were associated with a significant
      prolongation of survival time after intraperitoneal inoculation of the 22L prion
      strain. Moreover, when circulating cholesterol levels rose after feeding PLTP
      deficient mice a lipid-enriched diet, a significant reduction in survival time of
      mice together with a marked increase in the accumulation rate of PrPSc deposits
      in their brain were observed. Our results suggest that the circulating
      cholesterol level is a determinant of prion propagation in vivo and that
      cholesterol-lowering strategies might be a successful therapeutic approach for
      patients suffering from prion diseases.

PMID- 28765210
TI  - An interview with Jim Smith.
AB  - Jim Smith is Director of Science at the Wellcome Trust and a group leader at the
      Francis Crick Institute, where he was formerly Director of Research. A Fellow of
      both the Royal Society and the Academy of Medical Sciences, he was knighted for
      his services to medical research and science education in 2016. His lab works on
      mesoderm induction in the early vertebrate embryo. We met Jim in the Crick to
      hear about his life in science, his visions for the Crick and the Wellcome Trust,
      and his advice for early career scientists.

PMID- 28765212
TI  - Programming and reprogramming the brain: a meeting of minds in neural fate.
AB  - In early April 2017, over 130 delegates met in Munich, Germany, to discuss the
      latest research in the development and reprogramming of cells of the nervous
      system. The conference, which was organised by Abcam and entitled 'Programming
      and Reprogramming the Brain', was a great success, and provided an excellent
      snapshot of the current state of the field, and what the challenges are for the
      future. This Meeting Review provides a summary of the talks presented and the
      major themes that emerged from the conference.

PMID- 28765211
TI  - The Zahn drawings: new illustrations of Xenopus embryo and tadpole stages for
      studies of craniofacial development.
AB  - The embryos and tadpoles of the frog Xenopus are increasingly important subjects
      for studies of the development of the head and face - studies that are providing
      novel and crucial insight into the causes and prevention of a suite of
      devastating birth defects, as well as basic evolutionary and developmental
      biology. However, many studies are conducted on a range of embryonic stages that
      are not fully represented in the beloved Xenopus resource, Nieuwkoop and Faber's
      classic Normal Table of Xenopus laevis (Daudin) The lack of standardized images
      at these stages acts as a barrier to the efficient and accurate representation
      and communication of experimental methodology and expression data. To fill this
      gap, we have created 27 new high-quality illustrations. Like their oft-used
      predecessors from Nieuwkoop and Faber, these drawings can be freely downloaded
      and used, and will, we hope, serve as an essential resource for this important
      model system.

PMID- 28765213
TI  - KRAB zinc finger proteins.
AB  - Kruppel-associated box domain zinc finger proteins (KRAB-ZFPs) are the largest
      family of transcriptional regulators in higher vertebrates. Characterized by an N
      terminal KRAB domain and a C-terminal array of DNA-binding zinc fingers, they
      participate, together with their co-factor KAP1 (also known as TRIM28), in
      repression of sequences derived from transposable elements (TEs). Until recently,
      KRAB-ZFP/KAP1-mediated repression of TEs was thought to lead to irreversible
      silencing, and the evolutionary selection of KRAB-ZFPs was considered to be just
      the host component of an arms race against TEs. However, recent advances indicate
      that KRAB-ZFPs and their TE targets also partner up to establish species-specific
      regulatory networks. Here, we provide an overview of the KRAB-ZFP gene family,
      highlighting how its evolutionary history is linked to that of TEs, and how KRAB
      ZFPs influence multiple aspects of development and physiology.

PMID- 28765214
TI  - Epigenetic resetting of human pluripotency.
AB  - Much attention has focussed on the conversion of human pluripotent stem cells
      (PSCs) to a more naive developmental status. Here we provide a method for
      resetting via transient histone deacetylase inhibition. The protocol is effective
      across multiple PSC lines and can proceed without karyotype change. Reset cells
      can be expanded without feeders with a doubling time of around 24 h. WNT
      inhibition stabilises the resetting process. The transcriptome of reset cells
      diverges markedly from that of primed PSCs and shares features with human inner
      cell mass (ICM). Reset cells activate expression of primate-specific transposable
      elements. DNA methylation is globally reduced to a level equivalent to that in
      the ICM and is non-random, with gain of methylation at specific loci. Methylation
      imprints are mostly lost, however. Reset cells can be re-primed to undergo tri
      lineage differentiation and germline specification. In female reset cells,
      appearance of biallelic X-linked gene transcription indicates reactivation of the
      silenced X chromosome. On reconversion to primed status, XIST-induced silencing
      restores monoallelic gene expression. The facile and robust conversion routine
      with accompanying data resources will enable widespread utilisation,
      interrogation, and refinement of candidate naive cells.

PMID- 28765215
TI  - Methane-Fueled Syntrophy through Extracellular Electron Transfer: Uncovering the
      Genomic Traits Conserved within Diverse Bacterial Partners of Anaerobic
      Methanotrophic Archaea.
AB  - The anaerobic oxidation of methane by anaerobic methanotrophic (ANME) archaea in
      syntrophic partnership with deltaproteobacterial sulfate-reducing bacteria (SRB)
      is the primary mechanism for methane removal in ocean sediments. The mechanism of
      their syntrophy has been the subject of much research as traditional intermediate
      compounds, such as hydrogen and formate, failed to decouple the partners. Recent
      findings have indicated the potential for extracellular electron transfer from
      ANME archaea to SRB, though it is unclear how extracellular electrons are
      integrated into the metabolism of the SRB partner. We used metagenomics to
      reconstruct eight genomes from the globally distributed SEEP-SRB1 clade of ANME
      partner bacteria to determine what genomic features are required for syntrophy.
      The SEEP-SRB1 genomes contain large multiheme cytochromes that were not found in
      previously described free-living SRB and also lack periplasmic hydrogenases that
      may prevent an independent lifestyle without an extracellular source of electrons
      from ANME archaea. Metaproteomics revealed the expression of these cytochromes at
      in situ methane seep sediments from three sites along the Pacific coast of the
      United States. Phylogenetic analysis showed that these cytochromes appear to have
      been horizontally transferred from metal-respiring members of the
      Deltaproteobacteria such as Geobacter and may allow these syntrophic SRB to
      accept extracellular electrons in place of other chemical/organic electron
      donors.IMPORTANCE Some archaea, known as anaerobic methanotrophs, are capable of
      converting methane into carbon dioxide when they are growing syntopically with
      sulfate-reducing bacteria. This partnership is the primary mechanism for methane
      removal in ocean sediments; however, there is still much to learn about how this
      syntrophy works. Previous studies have failed to identify the metabolic
      intermediate, such as hydrogen or formate, that is passed between partners.
      However, recent analysis of methanotrophic archaea has suggested that the
      syntrophy is formed through direct electron transfer. In this research, we
      analyzed the genomes of multiple partner bacteria and showed that they also
      contain the genes necessary to perform extracellular electron transfer, which are
      absent in related bacteria that do not form syntrophic partnerships with
      anaerobic methanotrophs. This genomic evidence shows a possible mechanism for
      direct electron transfer from methanotrophic archaea into the metabolism of the
      partner bacteria.

PMID- 28765216
TI  - Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and
      Subsequent Innate Responses of Macrophages.
AB  - The scavenger receptor MARCO is expressed in several subsets of naive tissue
      resident macrophages and has been shown to participate in the recognition of
      various bacterial pathogens. However, the role of MARCO in antiviral defense is
      largely unexplored. Here, we investigated whether MARCO might be involved in the
      innate sensing of infection with adenovirus and recombinant adenoviral vectors by
      macrophages, which elicit vigorous immune responses in vivo Using cells derived
      from mice, we show that adenovirus infection is significantly more efficient in
      MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines
      (Max Planck Institute cells) than in MARCO-negative bone marrow-derived
      macrophages. Using antibodies blocking ligand binding to MARCO, as well as gene
      deficient and MARCO-transfected cells, we show that MARCO mediates the rapid
      adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO
      contributes to efficient innate virus recognition through the cytoplasmic DNA
      sensor cGAS. This leads to strong proinflammatory responses, including the
      production of interleukin-6 (IL-6), alpha/beta interferon, and mature IL-1alpha.
      These findings contribute to the understanding of viral pathogenesis in
      macrophages and may open new possibilities for the development of tools to
      influence the outcome of infection with adenovirus or adenovirus
      vectors.IMPORTANCE Macrophages play crucial roles in inflammation and defense
      against infection. Several macrophage subtypes have been identified with
      differing abilities to respond to infection with both natural adenoviruses and
      recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens
      that elicit vigorous innate responses in vitro and in vivo The cell surface
      receptors mediating macrophage type-specific adenovirus sensing are largely
      unknown. The scavenger receptor MARCO is expressed on some subsets of naive
      tissue-resident macrophages, including lung alveolar macrophages. Its role in
      antiviral macrophage responses is largely unexplored. Here, we studied whether
      the differential expression of MARCO might contribute to the various
      susceptibilities of macrophage subtypes to adenovirus. We demonstrate that MARCO
      significantly enhances adenovirus infection and innate responses in macrophages.
      These results help to understand adenoviral pathogenesis and may open new
      possibilities to influence the outcome of infection with adenoviruses or
      adenovirus vectors.

PMID- 28765217
TI  - RIP-Seq Suggests Translational Regulation by L7Ae in Archaea.
AB  - L7Ae is a universal archaeal protein that recognizes and stabilizes kink-turn (k
      turn) motifs in RNA substrates. These structural motifs are widespread in nature
      and are found in many functional RNA species, including ribosomal RNAs. Synthetic
      biology approaches utilize L7Ae/k-turn interactions to control gene expression in
      eukaryotes. Here, we present results of comprehensive RNA immunoprecipitation
      sequencing (RIP-Seq) analysis of genomically tagged L7Ae from the
      hyperthermophilic archaeon Sulfolobus acidocaldarius A large set of interacting
      noncoding RNAs was identified. In addition, several mRNAs, including the l7ae
      transcript, were found to contain k-turn motifs that facilitate L7Ae binding. In
      vivo studies showed that L7Ae autoregulates the translation of its mRNA by
      binding to a k-turn motif present in the 5' untranslated region (UTR). A green
      fluorescent protein (GFP) reporter system was established in Escherichia coli and
      verified conservation of L7Ae-mediated feedback regulation in Archaea Mobility
      shift assays confirmed binding to a k-turn in the transcript of nop5-fibrillarin,
      suggesting that the expression of all C/D box sRNP core proteins is regulated by
      L7Ae. These studies revealed that L7Ae-mediated gene regulation evolved in
      archaeal organisms, generating new tools for the modulation of synthetic gene
      circuits in bacteria.IMPORTANCE L7Ae is an essential archaeal protein that is
      known to structure ribosomal RNAs and small RNAs (sRNAs) by binding to their kink
      turn motifs. Here, we utilized RIP-Seq methodology to achieve a first global
      analysis of RNA substrates for L7Ae. Several novel interactions with noncoding
      RNA molecules (e.g., with the universal signal recognition particle RNA) were
      discovered. In addition, L7Ae was found to bind to mRNAs, including its own
      transcript's 5' untranslated region. This feedback-loop control is conserved in
      most archaea and was incorporated into a reporter system that was utilized to
      control gene expression in bacteria. These results demonstrate that L7Ae-mediated
      gene regulation evolved originally in archaeal organisms. The feedback-controlled
      reporter gene system can easily be adapted for synthetic biology approaches that
      require strict gene expression control.

PMID- 28765218
TI  - Dengue Virus-Infected Dendritic Cells, but Not Monocytes, Activate Natural Killer
      Cells through a Contact-Dependent Mechanism Involving Adhesion Molecules.
AB  - Natural killer (NK) cells play a protective role against dengue virus (DENV)
      infection, but the cellular and molecular mechanisms are not fully understood.
      Using an optimized humanized mouse model, we show that human NK cells, through
      the secretion of gamma interferon (IFN-gamma), are critical in the early defense
      against DENV infection. Depletion of NK cells or neutralization of IFN-gamma
      leads to increased viremia and more severe thrombocytopenia and liver damage in
      humanized mice. In vitro studies using autologous human NK cells show that DENV
      infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK
      cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25
      and secretion of IFN-gamma. Blocking adhesion molecules (LFA-1, DNAM-1, CD2, and
      2beta4) on NK cells abolishes NK cell activation, IFN-gamma secretion, and the
      control of DENV replication. NK cells activated by infected MDDCs also inhibit
      DENV infection in monocytes. These findings show the essential role of human NK
      cells in protection against acute DENV infection in vivo, identify adhesion
      molecules and dendritic cells required for NK cell activation, and delineate the
      sequence of events for NK cell activation and protection against DENV
      infection.IMPORTANCE Dengue is a mosquito-transmitted viral disease with a range
      of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The
      diverse disease manifestation is thought to result from a complex interplay
      between viral and host factors. Using mice engrafted with a human immune system,
      we show that human NK cells inhibit virus infection through secretion of the
      cytokine gamma interferon and reduce disease pathogenesis, including depletion of
      platelets and liver damage. During a natural infection, DENV initially infects
      dendritic cells in the skin. We find that NK cells interact with infected
      dendritic cells through physical contact mediated by adhesion molecules and
      become activated before they can control virus infection. These results show a
      critical role of human NK cells in controlling DENV infection in vivo and reveal
      the sequence of molecular and cellular events that activate NK cells to control
      dengue virus infection.

PMID- 28765219
TI  - Genomic Dissection of an Icelandic Epidemic of Respiratory Disease in Horses and
      Associated Zoonotic Cases.
AB  - Iceland is free of the major infectious diseases of horses. However, in 2010 an
      epidemic of respiratory disease of unknown cause spread through the country's
      native horse population of 77,000. Microbiological investigations ruled out known
      viral agents but identified the opportunistic pathogen Streptococcus equi subsp.
      zooepidemicus (S. zooepidemicus) in diseased animals. We sequenced the genomes of
      257 isolates of S. zooepidemicus to differentiate epidemic from endemic strains.
      We found that although multiple endemic clones of S. zooepidemicus were present,
      one particular clone, sequence type 209 (ST209), was likely to have been
      responsible for the epidemic. Concurrent with the epidemic, ST209 was also
      recovered from a human case of septicemia, highlighting the pathogenic potential
      of this strain. Epidemiological investigation revealed that the incursion of this
      strain into one training yard during February 2010 provided a nidus for the
      infection of multiple horses that then transmitted the strain to farms throughout
      Iceland. This study represents the first time that whole-genome sequencing has
      been used to investigate an epidemic on a national scale to identify the likely
      causative agent and the link to an associated zoonotic infection. Our data
      highlight the importance of national biosecurity to protect vulnerable
      populations of animals and also demonstrate the potential impact of S.
      zooepidemicus transmission to other animals, including humans.IMPORTANCE An
      epidemic of respiratory disease affected almost the entire native Icelandic horse
      population of 77,000 animals in 2010, resulting in a self-imposed ban on the
      export of horses and significant economic costs to associated industries.
      Although the speed of transmission suggested that a viral pathogen was
      responsible, only the presence of the opportunistic pathogen Streptococcus
      zooepidemicus was consistent with the observed clinical signs. We applied genomic
      sequencing to differentiate epidemic from endemic strains and to shed light on
      the rapid transmission of the epidemic strain throughout Iceland. We further
      highlight the ability of epidemic and endemic strains of S. zooepidemicus to
      infect other animals, including humans. This study represents the first time that
      whole-genome sequencing has been used to elucidate an outbreak on a national
      scale and identify the likely causative agent.

PMID- 28765220
TI  - Nitrite Derived from Endogenous Bacterial Nitric Oxide Synthase Activity Promotes
      Aerobic Respiration.
AB  - Macrophage-derived nitric oxide (NO.) is a crucial effector against invading
      pathogens. Yet, paradoxically, several bacterial species, including some
      pathogens, are known to endogenously produce NO. via nitric oxide synthase (NOS)
      activity, despite its apparent cytotoxicity. Here, we reveal a conserved role for
      bacterial NOS in activating aerobic respiration. We demonstrate that nitrite
      generated from endogenous NO. decomposition stimulates quinol oxidase activity in
      Staphylococcus aureus and increases the rate of cellular respiration. This not
      only supports optimal growth of this organism but also prevents a dysbalance in
      central metabolism. Further, we also show that activity of the SrrAB two
      component system alleviates the physiological defects of the nos mutant. Our
      findings suggest that NOS and SrrAB constitute two distinct but functionally
      redundant routes for controlling staphylococcal respiration during aerobic
      growth.IMPORTANCE Despite its potential autotoxic effects, several bacterial
      species, including pathogenic staphylococcal species, produce NO. endogenously
      through nitric oxide synthase (NOS) activity. Therefore, how endogenous NO.
      influences bacterial fitness remains unclear. Here we show that the oxidation of
      NO. to nitrite increases aerobic respiration and consequently optimizes central
      metabolism to favor growth. Importantly, we also demonstrate that cells have a
      "fail-safe" mechanism that can maintain respiratory activity through the SrrAB
      two-component signaling regulon should NOS-derived nitrite levels decrease. These
      findings identify NOS and SrrAB as critical determinants of staphylococcal
      respiratory control and highlight their potential as therapeutic targets.

PMID- 28765221
TI  - Signal Peptide Hydrophobicity Modulates Interaction with the Twin-Arginine
      Translocase.
AB  - The general secretory pathway (Sec) and twin-arginine translocase (Tat) operate
      in parallel to export proteins across the cytoplasmic membrane of prokaryotes and
      the thylakoid membrane of plant chloroplasts. Substrates are targeted to their
      respective machineries by N-terminal signal peptides that share a tripartite
      organization; however, Tat signal peptides harbor a conserved and almost
      invariant arginine pair that is critical for efficient targeting to the Tat
      machinery. Tat signal peptides interact with a membrane-bound receptor complex
      comprised of TatB and TatC components, with TatC containing the twin-arginine
      recognition site. Here, we isolated suppressors in the signal peptide of the Tat
      substrate, SufI, that restored Tat transport in the presence of inactivating
      substitutions in the TatC twin-arginine binding site. These suppressors increased
      signal peptide hydrophobicity, and copurification experiments indicated that they
      restored binding to the variant TatBC complex. The hydrophobic suppressors could
      also act in cis to suppress substitutions at the signal peptide twin-arginine
      motif that normally prevent targeting to the Tat pathway. Highly hydrophobic
      variants of the SufI signal peptide containing four leucine substitutions
      retained the ability to interact with the Tat system. The hydrophobic signal
      peptides of two Sec substrates, DsbA and OmpA, containing twin lysine residues,
      were shown to mediate export by the Tat pathway and to copurify with TatBC. These
      findings indicate that there is unprecedented overlap between Sec and Tat signal
      peptides and that neither the signal peptide twin-arginine motif nor the TatC
      twin-arginine recognition site is an essential mechanistic feature for operation
      of the Tat pathway.IMPORTANCE Protein export is an essential process in all
      prokaryotes. The Sec and Tat export pathways operate in parallel, with the Sec
      machinery transporting unstructured precursors and the Tat pathway transporting
      folded proteins. Proteins are targeted to the Tat pathway by N-terminal signal
      peptides that contain an almost invariant twin-arginine motif. Here, we make the
      surprising discovery that the twin arginines are not essential for recognition of
      substrates by the Tat machinery and that this requirement can be bypassed by
      increasing the signal peptide hydrophobicity. We further show that signal
      peptides of bona fide Sec substrates can also mediate transport by the Tat
      pathway. Our findings suggest that key features of the Tat targeting mechanism
      have evolved to prevent mistargeting of substrates to the Sec pathway rather than
      being a critical requirement for function of the Tat pathway.

PMID- 28765222
TI  - Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent
      Virulence Factor Expression in Staphylococcus aureus.
AB  - The SaeRS two-component system is a master activator of virulence factor
      transcription in Staphylococcus aureus, but the cellular factors that control its
      activity are unknown. Fatty acid (FA) kinase is a two-component enzyme system
      required for extracellular FA uptake and SaeRS activity. Here, we demonstrate the
      existence of an intracellular nonesterified FA pool in S. aureus that is elevated
      in strains lacking FA kinase activity. SaeRS-mediated transcription is restored
      in FA kinase-negative strains when the intracellular FA pool is reduced either by
      growth with FA-depleted bovine serum albumin to extract the FA into the medium or
      by the heterologous expression of Neisseria gonorrhoeae acyl-acyl carrier protein
      synthetase to activate FA for phospholipid synthesis. These data show that FAs
      act as negative regulators of SaeRS signaling, and FA kinase activates SaeRS
      dependent virulence factor production by lowering inhibitory FA levels. Thus, FA
      kinase plays a role in cellular lipid homeostasis by activating FA for
      incorporation into phospholipid, and it indirectly regulates SaeRS signaling by
      maintaining a low intracellular FA pool.IMPORTANCE The SaeRS two-component system
      is a master transcriptional activator of virulence factor production in response
      to the host environment in S. aureus, and strains lacking FA kinase have severely
      attenuated SaeRS-dependent virulence factor transcription. FA kinase is required
      for the activation of exogenous FAs, and it plays a role in cellular lipid
      homeostasis by recycling cellular FAs into the phospholipid biosynthetic pathway.
      Activation of the sensor kinase, SaeS, is mediated by its membrane anchor domain,
      and the FAs which accumulate in FA kinase knockout strains are potent inhibitors
      of SaeS-dependent signaling. This work identifies FAs as physiological effectors
      for the SaeRS system and reveals a connection between cellular lipid homeostasis
      and the regulation of virulence factor transcription. FA kinase is widely
      distributed in Gram-positive bacteria, suggesting similar roles for FA kinase in
      these organisms.

PMID- 28765223
TI  - Elongation Factor P Interactions with the Ribosome Are Independent of Pausing.
AB  - Bacterial elongation factor P (EF-P) plays a pivotal role in the translation of
      polyproline motifs. To stimulate peptide bond formation, EF-P must enter the
      ribosome via an empty E-site. Using fluorescence-based single-molecule tracking,
      Mohapatra et al. (S. Mohapatra, H. Choi, X. Ge, S. Sanyal, and J. C. Weisshaar,
      mBio 8:e00300-17, 2017, https://doi.org/10.1128/mBio.00300-17) monitored the
      cellular distribution of EF-P and quantified the frequency of association between
      EF-P and the ribosome under various conditions. Findings from the study showed
      that EF-P has a localization pattern that is strikingly similar to that of
      ribosomes. Intriguingly, EF-P was seen to bind ribosomes more frequently than the
      estimated number of pausing events, indicating that E-site vacancies occur even
      when ribosomes are not paused. The study provides new insights into the mechanism
      of EF-P-dependent peptide bond formation and the intricacies of translation
      elongation.

PMID- 28765226
TI  - The Impact of the Impact Factor.

PMID- 28765224
TI  - Genome-Wide Sensitivity Analysis of the Microsymbiont Sinorhizobium meliloti to
      Symbiotically Important, Defensin-Like Host Peptides.
AB  - The model legume species Medicago truncatula expresses more than 700 nodule
      specific cysteine-rich (NCR) signaling peptides that mediate the differentiation
      of Sinorhizobium meliloti bacteria into nitrogen-fixing bacteroids. NCR peptides
      are essential for a successful symbiosis in legume plants of the inverted-repeat
      lacking clade (IRLC) and show similarity to mammalian defensins. In addition to
      signaling functions, many NCR peptides exhibit antimicrobial activity in vitro
      and in vivo Bacterial resistance to these antimicrobial activities is likely to
      be important for symbiosis. However, the mechanisms used by S. meliloti to resist
      antimicrobial activity of plant peptides are poorly understood. To address this,
      we applied a global genetic approach using transposon mutagenesis followed by
      high-throughput sequencing (Tn-seq) to identify S. meliloti genes and pathways
      that increase or decrease bacterial competitiveness during exposure to the well
      studied cationic NCR247 peptide and also to the unrelated model antimicrobial
      peptide polymyxin B. We identified 78 genes and several diverse pathways whose
      interruption alters S. meliloti resistance to NCR247. These genes encode the
      following: (i) cell envelope polysaccharide biosynthesis and modification
      proteins, (ii) inner and outer membrane proteins, (iii) peptidoglycan (PG)
      effector proteins, and (iv) non-membrane-associated factors such as
      transcriptional regulators and ribosome-associated factors. We describe a
      previously uncharacterized yet highly conserved peptidase, which protects S.
      meliloti from NCR247 and increases competitiveness during symbiosis.
      Additionally, we highlight a considerable number of uncharacterized genes that
      provide the basis for future studies to investigate the molecular basis of
      symbiotic development as well as chronic pathogenic interactions.IMPORTANCE Soil
      rhizobial bacteria enter into an ecologically and economically important
      symbiotic interaction with legumes, in which they differentiate into
      physiologically distinct bacteroids that provide essential ammonia to the plant
      in return for carbon sources. Plant signal peptides are essential and specific to
      achieve these physiological changes. These peptides show similarity to mammalian
      defensin peptides which are part of the first line of defense to control invading
      bacterial populations. A number of these legume peptides are indeed known to
      possess antimicrobial activity, and so far, only the bacterial BacA protein is
      known to protect rhizobial bacteria against their antimicrobial action. This
      study identified numerous additional bacterial factors that mediate protection
      and belong to diverse biological pathways. Our results significantly contribute
      to our understanding of the molecular roles of bacterial factors during legume
      symbioses and, second, provide insights into the mechanisms that pathogenic
      bacteria may use to resist the antimicrobial effects of defensins during
      infections.

PMID- 28765227
TI  - Determination of an Optimal Pharmacokinetic Model of 18F-FET for Quantitative
      Applications in Rat Brain Tumors.
AB  - O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) is a radiolabeled artificial amino
      acid used in PET for tumor delineation and grading. The present study compares
      different kinetic models to determine which are more appropriate for 18F-FET in
      rats. Methods: Rats were implanted with F98 glioblastoma cells in the right
      hemisphere and scanned 9-15 d later. PET data were acquired during 50 min after a
      1-min bolus of 18F-FET. Arterial blood samples were drawn for arterial input
      function determination. Two compartmental pharmacokinetic models were tested: the
      2-tissue model and the 1-tissue model. Their performance at fitting concentration
      curves from regions of interest was evaluated using the Akaike information
      criterion, F test, and residual plots. Graphical models were assessed
      qualitatively. Results: Metrics indicated that the 2-tissue model was superior to
      the 1-tissue model for the current dataset. The 2-tissue model allowed adequate
      decoupling of 18F-FET perfusion and internalization by cells in the different
      regions of interest. Of the 2 graphical models tested, the Patlak plot provided
      adequate results for the tumor and brain, whereas the Logan plot was appropriate
      for muscles. Conclusion: The 2-tissue-compartment model is appropriate to
      quantify the perfusion and internalization of 18F-FET by cells in various tissues
      of the rat, whereas graphical models provide a global measure of uptake.

PMID- 28765225
TI  - B Cell Requirement for Robust Regulatory T Cell Responses to Friend Retrovirus
      Infection.
AB  - Regulatory T cells (Tregs) are immunosuppressive cells of the immune system that
      control autoimmune reactivity. Tregs also respond during immune reactions to
      infectious agents in order to limit immunopathological damage from potent
      effectors such as CD8+ cytolytic T lymphocytes. We have used the Friend virus
      (FV) model of retroviral infection in mice to investigate how viral infections
      induce Tregs. During acute FV infection, there is significant activation and
      expansion of thymus-derived (natural) Tregs that suppress virus-specific CD8+ T
      cell responses. Unlike conventional T cells, the responding Tregs are not virus
      specific, so the mechanisms that induce their expansion are of great interest. We
      now show that B cells provide essential signals for Treg expansion during FV
      infection. Treg responses are greatly diminished in B cell-deficient mice but can
      be restored by adoptive transfers of B cells at the time of infection. The feeble
      Treg responses in B cell-deficient mice are associated with enhanced virus
      specific CD8+ T cell responses and accelerated virus control during the first 2
      weeks of infection. In vitro experiments demonstrated that B cells promote Treg
      activation and proliferation through a glucocorticoid-induced receptor
      superfamily member 18 (GITR) ligand-dependent mechanism. Thus, B cells play
      paradoxically opposing roles during FV infection. They provide proliferative
      signals to immunsosuppressive Tregs, which slows early virus control, and they
      also produce virus-specific antibodies, which are essential for long-term virus
      control.IMPORTANCE When infectious agents invade a host, numerous immunological
      mechanisms are deployed to limit their replication, neutralize their spread, and
      destroy the host cells harboring the infection. Since immune responses also have
      a strong capacity to damage host cells and tissues, their magnitude, potency, and
      duration are under regulatory control. Regulatory T cells are an important
      component of this control, and the mechanisms that induce them to respond and
      exert immunosuppressive regulation are of great interest. In the current report,
      we show that B cells, the cells responsible for making pathogen-specific
      antibodies, are also involved in promoting the expansion of regulatory T cells
      during a retroviral infection. In vitro studies demonstrated that they do so via
      stimulation of the Tregs through interactions between cell surface molecules:
      GITR interactions with its ligand (GITRL) on B cells and GITR on regulatory T
      cells. These findings point the way toward therapeutics to better treat
      infections and autoimmune diseases.

PMID- 28765228
TI  - Joint SNMMI-ASNC Expert Consensus Document on the Role of 18F-FDG PET/CT in
      Cardiac Sarcoid Detection and Therapy Monitoring.

PMID- 28765229
TI  - New Officers for SNMMI and SNMMI-TS.

PMID- 28765230
TI  - Lassmann Recognized with Loevinger-Berman Award.

PMID- 28765232
TI  - USP to Establish New General Chapter on Compounding.

PMID- 28765231
TI  - SNMMI New Fellows Honored.

PMID- 28765234
TI  - New Grants for TBI Research Previewed.

PMID- 28765236
TI  - SNMMI Leadership Update: The SNMMI 2017 Annual Meeting: Ushering in the Future
      with a Focus on Theranostics, Research, Education, and Value.

PMID- 28765235
TI  - Letter to the Editor: AUC for V/Q Imaging in Pulmonary Embolism. The Elephant in
      the Room: Planar or SPECT V/Q?

PMID- 28765238
TI  - SNMMI Annual Meeting Highlights Theranostics, Novel Research, and Image of the
      Year.

PMID- 28765237
TI  - Science Briefs from the SNMMI 2017 Annual Meeting.

PMID- 28765240
TI  - Proposed Core Set of Items for Measuring Disease Activity in Systemic Juvenile
      Idiopathic Arthritis.
AB  - OBJECTIVE: To date, there are no standardized disease activity tools for systemic
      juvenile idiopathic arthritis (sJIA). We developed a core set of disease activity
      measures for sJIA. METHODS: We conducted a validation study in patients with sJIA
      recruited from 3 Canadian institutions. Disease activity scores were based on
      questionnaires, clinical factors, and laboratory measures. The physician's global
      assessment was our criterion standard. We determined the strength of association
      of each item with the criterion standard. We then surveyed international experts
      to determine the top 10 items. Finally, we used the experts' responses to
      generate a proposed core set of disease activity measures. RESULTS: We enrolled
      57 subjects - 26 with moderately or severely active disease, and 31 with mildly
      active or inactive disease. Items that most strongly correlated with the
      criterion standard were number of active joints (r = 0.79), parent's global
      assessment of disease activity (r = 0.53), erythrocyte sedimentation rate (ESR; r
      = 0.62), and C-reactive protein (CRP; r = 0.61). The response rate from
      international experts was 82% (154/187). Items with the most votes, in descending
      order, were number of active joints, number of days with fever in the preceding 2
      weeks, patient's and parent's global assessments of disease activity, sJIA rash,
      ESR, CRP, and hemoglobin level. CONCLUSION: We propose a core set of items for
      measuring disease activity in sJIA. Future research should be aimed at further
      validation of this core set in the international context.

PMID- 28765241
TI  - A Multicenter Nominal Group Study to Rank Outcomes Important to Patients, and
      Their Representation in Existing Composite Outcome Measures for Psoriatic
      Arthritis.
AB  - OBJECTIVE: To rank outcomes identified as important to patients with psoriatic
      arthritis (PsA) and examine their representation in existing composite measures.
      METHODS: Seven nominal group technique (NGT) meetings took place at 4 hospital
      sites. Two sorting rounds were conducted to generate a shortlist of outcomes
      followed by a group discussion and final ranking. In the final ranking round,
      patients were given 15 points each and asked to rank their top 5 outcomes from
      the shortlist. The totals were summed across the 7 NGT groups and were presented
      as a percentage of the maximum possible priority score. RESULTS: Thirty-one
      patients took part: 16 men and 15 women; the mean age was 54 years (range 24-77;
      SD 12.2), the mean disease duration was 10.3 years (range 1-40; SD 9.2), and mean
      Health Assessment Questionnaire was 1.15 (range 0-2.63; SD 0.7). The highest
      ranked outcomes that patients wished to see from treatment were pain with 93
      points (20.0%), fatigue 62 (13.3%), physical fitness 33 (7.1%), halting/slowing
      damage 32 (6.9%), and quality of life/well-being 29 (6.2%). Reviewing existing
      composite measures for PsA demonstrated that no single measure adequately
      identifies all these outcomes. CONCLUSION: Pain and fatigue were ranked as the
      outcomes most important to patients receiving treatment for PsA and are not well
      represented within existing composite measures. Future work will focus on
      validating composite measures modified to identify outcomes important to
      patients.

PMID- 28765242
TI  - Pulmonary Involvement in Antineutrophil Cytoplasmic Antibodies (ANCA)-associated
      Vasculitis: The Influence of ANCA Subtype.
AB  - OBJECTIVE: To describe pulmonary involvement at time of diagnosis in
      antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), as
      defined by computed tomography (CT). METHODS: Patients with thoracic CT performed
      on or after the onset of AAV (n = 140; 75 women; granulomatosis with
      polyangiitis, n = 79; microscopic polyangiitis MPA, n = 61) followed at a
      tertiary referral center vasculitis clinic were studied. Radiological patterns of
      pulmonary involvement were evaluated from the CT studies using a predefined
      protocol, and compared to proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA
      specificity. RESULTS: Of the patients, 77% had an abnormal thoracic CT study. The
      most common abnormality was nodular disease (24%), of which the majority were
      peribronchial nodules, followed by bronchiectasis and pleural effusion (19%,
      each), pulmonary hemorrhage and lymph node enlargement (14%, each), emphysema
      (13%), and cavitating lesions (11%). Central airways disease and a nodular
      pattern of pulmonary involvement were more common in PR3-ANCA-positive patients
      (p < 0.05). Usual interstitial pneumonitis (UIP) and bronchiectasis were more
      prevalent in MPO-ANCA-positive patients (p < 0.05). Alveolar hemorrhage, pleural
      effusion, lymph node enlargement, and pulmonary venous congestion were more
      frequent in MPO-ANCA-positive patients. CONCLUSION: Pulmonary involvement is
      frequent and among 140 patients with AAV who underwent a thoracic CT study,
      almost 80% have pulmonary abnormalities on thoracic CT. Central airway disease
      occurs exclusively among patients with PR3-ANCA while UIP were mainly seen in
      those with MPO-ANCA. These findings may have important implications for the
      investigation, management, and pathogenesis of AAV.

PMID- 28765243
TI  - Corticosteroid or Nonsteroidal Antiinflammatory Drugs for the Treatment of Acute
      Gout: A Systematic Review of Randomized Controlled Trials.
AB  - OBJECTIVE: Nonsteroidal antiinflammatory drugs (NSAID) are used as first-line
      agents to treat acute gout. Recent trials suggest a possible first-line role for
      corticosteroids. METHODS: We conducted a metaanalysis of randomized controlled
      trials (RCT) evaluating corticosteroid versus NSAID therapy (nonselective and
      selective) as treatment for acute gout. MEDLINE, EMBASE, and CENTRAL were
      systematically searched through August 2016. Outcomes included pain, bleeding,
      joint swelling, erythema, tenderness, activity limitation, response to therapy,
      quality of life, time to resolution, supplementary analgesics, and adverse
      events. Evidence quality was summarized using the GRADE (Grading of
      Recommendations Assessment, Development, and Evaluation) system. RESULTS: Six
      eligible trials (817 patients) were identified. The mean study followup was 15
      days (range 4-30). Risks of bias were generally low. In low- to moderate-quality
      evidence, corticosteroids did not have different effects on pain score at < 7
      days [standardized mean difference (SMD) -0.09, 95% CI -0.26 to 0.08] or at >= 7
      days (SMD 0.32, 95% CI -0.27 to 0.92) when compared with NSAID. There was no
      evidence of different risks of gastrointestinal bleeding [relative risk (RR)
      0.09, 95% CI 0.01-1.67]. There was no evidence of different responses to therapy
      on pain at < 7 days (RR 1.07, 95% CI 0.80-1.44) and >= 7 days, time to disease
      resolution, or number of supplementary analgesics used (MD 2.10 drugs, 95% CI 
      1.01 to 5.21). There was a lower risk of indigestion (RR 0.50, 95% CI 0.27-0.92),
      nausea (RR 0.25, 95% CI 0.11-0.54), and vomiting (RR 0.11, 95% CI 0.02-0.56) with
      corticosteroid therapy. CONCLUSION: There is no evidence that corticosteroids and
      NSAID have different efficacy in managing pain in acute gout, but corticosteroids
      appear to have a more favorable safety profile for selected adverse events
      analyzed in existing RCT.

PMID- 28765239
TI  - Toward the Development of a Core Set of Outcome Domains to Assess Shared Decision
      making Interventions in Rheumatology: Results from an OMERACT Delphi Survey and
      Consensus Meeting.
AB  - OBJECTIVE: The aim of this Outcome Measures in Rheumatology (OMERACT) Working
      Group was to determine the core set of outcome domains and subdomains for
      measuring the effectiveness of shared decision-making (SDM) interventions in
      rheumatology clinical trials. METHODS: Following the OMERACT Filter 2.0, and
      based on a previous literature review of SDM outcome domains and a nominal group
      process at OMERACT 2014, (1) an online Delphi survey was conducted to gather
      feedback on the draft core set and refine its domains and subdomains, and (2) a
      workshop was held at the OMERACT 2016 meeting to gain consensus on the draft core
      set. RESULTS: A total of 170 participants completed Round 1 of the Delphi survey,
      and 116 completed Round 2. Respondents came from 29 countries, with 49% being
      patients/caregivers. Results showed that 14 out of the 17 subdomains within the 7
      domains exceeded the 70% criterion (endorsement ranged from 83% to 100% of
      respondents). At OMERACT 2016, only 8% of the 96 attendees were
      patients/caregivers. Despite initial votes of support in breakout groups, there
      was insufficient comfort about the conceptualization of these 7 domains and 17
      subdomains for these to be endorsed at OMERACT 2016 (endorsement ranged from 17%
      to 68% of participants). CONCLUSION: Differences between the Delphi survey and
      consensus meeting may be explained by the manner in which the outcomes were
      presented, variations in participant characteristics, and the context of voting.
      Further efforts are needed to address the limited understanding of SDM and its
      outcomes among OMERACT participants.

PMID- 28765244
TI  - Five Potentially Modifiable Factors Predict Poor Quality of Life in Ankylosing
      Spondylitis: Results from the Scotland Registry for Ankylosing Spondylitis.
AB  - OBJECTIVE: A chronic inflammatory condition manifesting in young adulthood,
      ankylosing spondylitis (AS) affects both physical and emotional quality of life
      (QOL). To inform future intervention strategies, this study aimed to (1) assess
      the QOL of patients with AS, and (2) identify potentially modifiable factors
      associated with reporting poor QOL. METHODS: The Scotland Registry for Ankylosing
      Spondylitis collects clinical and patient-reported data on clinically diagnosed
      patients with AS across Scotland. QOL is measured using the ASQoL questionnaire
      [range: 0 (high) to 18 (poor)]. Potentially modifiable factors associated with
      reporting poor QOL (score 12-18) were examined using Poisson regression models,
      adjusted for a variety of demographic characteristics, plus various nonmodifiable
      factors. Results are given as risk ratios (RR) with 95% CI. RESULTS: Data were
      available on 959 patients: 74% male, mean age 52 years (SD 13), median ASQoL 7.0
      (interquartile range 2-12). Although many factors were univariately associated
      with poor QOL, 5 were identified as independent predictors: reporting
      moderate/severe fatigue (RR 1.60, 95% CI 1.13-2.28), poor physical function [Bath
      Ankylosing Spondylitis Functional Index (BASFI) >= 4: 3.46, 1.76-6.82], chronic
      widespread pain (CWP; 1.92, 1.33-2.75), high disease activity [Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) >= 4: 1.52, 1.09-2.12], and poor
      spinal mobility [Bath Ankylosing Spondylitis Metrology Index (BASMI) >= 4: 1.52,
      0.93-2.50]. For these factors, population-attributable risks ranged between 20%
      (disease activity) and 56% (physical function). CONCLUSION: We have identified 5
      potentially modifiable factors independently associated with poor QOL. These
      findings provide evidence that in addition to traditional clinical targets
      (BASDAI, BASFI, and BASMI), focus on nonspecific symptoms (CWP and fatigue),
      perhaps with nonpharmacological therapies, may yield important improvements in
      QOL.

PMID- 28765245
TI  - Advancing the Development of Patient-reported Outcomes for Adult Myositis at
      OMERACT 2016: An International Delphi Study.
AB  - OBJECTIVE: To define a set of core patient-reported domains and respective
      instruments for use in idiopathic inflammatory myopathies (IIM). Previously, we
      reported a systematic literature review on patient-reported outcomes (PRO) in IIM
      followed by conducting international focus groups to elicit patient perspectives
      of myositis symptoms and effects. METHODS: Based on qualitative content analysis
      of focus groups, an initial list of 26 candidate domains was constructed. We
      subsequently conducted an international modified Delphi survey to identify the
      importance of each of the 26 domains. Participants were asked to rate each domain
      on a scale of 0-10 (0 = not important, 10 = very important). RESULTS: In this
      first round of the Delphi survey, 643 patients participated from the United
      States (n = 543), Sweden (n = 49), and South Korea (n = 51). Of the 26 domains,
      19 (73%) were rated of high importance (>= 7/10). The top 5 domains were muscle
      symptoms, fatigue, interactions with healthcare, medication side effects, and
      pain. During Outcome Measures in Rheumatology (OMERACT) 2016, we discussed the
      goal for ultimate reduction in the number of domains and the importance of
      considering representation of healthcare providers from other specialties,
      caregivers, representatives of pharmaceutical industries, and regulatory
      authorities in the next rounds of Delphi to represent broader perspectives on
      IIM. CONCLUSION: Further prioritization and a reduction in the number of domains
      will be needed for the next Delphi. At the next biennial OMERACT meeting, we aim
      to present and seek voting on a Myositis Preliminary PRO Core Set to enable
      ultimate measure selection and development.

PMID- 28765246
TI  - The OMERACT Core Domain Set for Outcome Measures for Clinical Trials in
      Polymyalgia Rheumatica.
AB  - OBJECTIVE: To inform development of a core domain set for outcome measures for
      clinical trials in polymyalgia rheumatica (PMR), we conducted patient
      consultations, a systematic review, a Delphi study, and 2 qualitative studies.
      METHODS: Domains identified by 70% or more of physicians and/or patients in the
      Delphi study were selected. The conceptual framework derived from the 2
      qualitative research studies helped inform the meaning of each domain and its
      relationship to the others. The draft core domain set was refined by further
      discussion with patients and physicians who had participated in the Delphi study.
      At the Outcome Measures in Rheumatology (OMERACT) 2016, the domains were
      discussed and prioritized by 8 breakout groups. Formal voting took place at the
      end of the workshop and in the final plenary. RESULTS: Ninety-three percent of
      voters in the final plenary agreed that the inner core of domains considered
      mandatory for clinical trials of PMR should consist the following: laboratory
      markers of systemic inflammation, pain, stiffness, and physical function.
      Patient's global and fatigue were considered important but not mandatory (outer
      core). The research agenda included psychological impact, weakness, physical
      activity, participation, sleep, imaging, and health-related quality of life.
      CONCLUSION: This core domain set was considered sufficiently well-defined that
      the next step will be to apply the OMERACT Filter 2.0 Instrument Selection
      Algorithm to select candidate instruments for a subsequent "deeper dive" into the
      data. This will allow instruments to be mapped onto each of our core domains to
      derive a core outcome set for PMR.

PMID- 28765247
TI  - A Longitudinal Study of Ambulatory Physician Encounters, Emergency Room Visits,
      and Hospitalizations by Patients with Rheumatoid Arthritis: A 13-year Population
      Health Study.
AB  - OBJECTIVE: To determine total physician encounters, emergency room (ER) visits,
      and hospitalizations in an incident cohort of rheumatoid arthritis (RA) cases and
      matched control patients over 13 years. METHODS: A retrospective cohort study was
      performed using administrative healthcare data from about 1 million people with
      access to universal healthcare. Using the International Classification of
      Diseases, 9th ed (ICD-9) and ICD-10 diagnostic codes, 7 RA case definitions were
      used. Each case was matched by age and sex to 4 randomly selected controls. Data
      included physician billings, ER visits, and hospital discharges over 13 years.
      RESULTS: The number of incident RA cases varied from 3497 to 27,694, depending on
      the case definition. The mean age varied from 54.3 to 65.0 years, and the
      proportion of women from 67.8% to 71.3%. The number of physician encounters by
      patients with RA was significantly higher than by controls. It was highest in the
      index year and declined promptly thereafter for all case definitions and by 12.2%
      46.8% after 10 years. Encounters with subspecialty physicians fell by 61%
      (rheumatologists) and 34% (internal medicine). In contrast, clinical encounters
      with family physicians and other physicians fell by only 9%. Visits to the ER and
      hospital admissions were also significantly higher in RA cases, particularly
      early in the disease, and fell significantly over the followup. CONCLUSION: In
      patients with RA, healthcare use is highest in the first year following the
      diagnosis, which is also the time of maximal involvement by rheumatologists. Use
      declines over time, and encounters with patients' family physicians predominate
      over other physician groups.

PMID- 28765248
TI  - Adherence and Persistence with Drug Therapy among Fibromyalgia Patients: Data
      from a Large Health Maintenance Organization.
AB  - OBJECTIVE: To assess 1-year persistence and adherence rates with drug therapy
      among patients with fibromyalgia (FM) and to identify factors associated with
      therapy discontinuation. METHODS: This retrospective, cohort study included
      members >= 21 years old from the Maccabi Healthcare Services, a large health
      maintenance organization in Israel, who were diagnosed with FM from 2008 through
      2011. Medications of interest included the anticonvulsant pregabalin,
      antidepressants [selective serotonin reuptake inhibitor (SSRI),
      serotonin/norepinephrine reuptake inhibitor (SNRI)], and tricyclic
      antidepressants (TCA). Time to treatment discontinuation and proportion of days
      covered (PDC) with FM-specific therapies during the year from first dispensed
      were analyzed. PDC < 20% was considered low adherence and PDC >= 80% was
      considered high adherence. Logistic regression models were constructed for
      multivariable analyses. RESULTS: Overall, 3932 patients with FM were included;
      88.7% were female. Pre-diagnosis use of medication of interest was documented in
      41% of the study population. Of the remaining 2312 patients, 56.1% were issued a
      prescription, 45.0% were dispensed at least 1 medication in the year following
      diagnosis, and only 28.8% had prescriptions filled twice within the first year
      from diagnosis. Among newly prescribed patients, 1-year discontinuation was
      highest for TCA (91.0%) and lowest for SSRI/SNRI antidepressants (73.7%). Over
      half of the patients (60.5%) had fewer than 20% of the days covered by any
      medication during the year and only 9.3% were very adherent (PDC >= 80%).
      CONCLUSION: This study clearly shows that in an Israeli "real-life" population of
      patients with FM, persistence and adherence with FM therapy in the year following
      diagnosis is remarkably low.

PMID- 28765249
TI  - Ultrasound Characteristics of the Achilles Tendon in Tophaceous Gout: A
      Comparison with Age- and Sex-matched Controls.
AB  - OBJECTIVE: To investigate the frequency and distribution of characteristics of
      the Achilles tendon (AT) in people with tophaceous gout using musculoskeletal
      ultrasound (US). METHODS: Twenty-four participants with tophaceous gout and 24
      age- and sex-matched controls without gout or other arthritis were recruited. All
      participants underwent a greyscale and power Doppler US examination. The AT was
      divided into 3 anatomical zones (insertion, pre-insertional, and proximal to the
      mid-section). The following US characteristics were assessed: tophus, tendon
      echogenicity, tendon vascularity, tendon morphology, entheseal characteristics,
      bursal morphology, and calcaneal bone profile. RESULTS: The majority of the
      participants with tophaceous gout were middle-aged men (n = 22, 92%)
      predominately of European ethnicity (n = 14, 58%). Tophus deposition was observed
      in 73% (n = 35) of tendons in those with gout and in none of the controls (p <
      0.01). Intratendinous hyperechoic spots (p < 0.01) and intratendinous power
      Doppler signal (p < 0.01) were more frequent in participants with gout compared
      to controls. High prevalence of entheseal calcifications, calcaneal bone cortex
      irregularities, and calcaneal enthesophytes were observed in both gout
      participants and controls, without differences between groups. Intratendinous
      structural damage was rare. Hyperechoic spots were significantly more common at
      the insertion compared to the zone proximal to the mid-section (p < 0.01), but
      between-zone differences were not observed for other features. CONCLUSION: US
      features of urate deposition, tophus, and vascularization are present throughout
      the AT in patients with tophaceous gout. Despite crystal deposition,
      intratendinous structural changes are infrequent. Many characteristics observed
      in the AT in people with tophaceous gout, particularly at the calcaneal enthesis,
      are not disease-specific.

PMID- 28765250
TI  - Validating Rheumatoid Arthritis Remission Using the Patients' Perspective:
      Results from a Special Interest Group at OMERACT 2016.
AB  - OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) working group on the
      patients' perspective on remission in rheumatoid arthritis (RA) has been working
      on this topic since 2010. At OMERACT 2016, progress and preliminary data on
      validity of measurement instruments for pain, fatigue, and independence in
      remission in RA were presented, and future directions were explored. METHODS: A
      special interest group was organized, in which the current data on the patients'
      perspective on remission were presented. The ongoing study that aimed to validate
      measurement instruments for pain, fatigue, and independence in a state of low
      disease activity or remission was presented, and preliminary data on construct
      validity and discriminative capacity were evaluated cross-sectionally. RESULTS:
      At OMERACT 2016, the progress of the working group and preliminary data from 142
      of the anticipated 300 patients were presented. Selected instruments
      significantly correlated with the Disease Activity Score in 28 joints (construct
      validity) and all instruments except 1 discriminated between patients in and
      patients not in remission. The subsequent discussion mainly focused around 3
      points: (1) the formulation of patient perceived remission, (2) the duration of
      remission, and (3) the measurement of the domain independence. An informal vote
      indicated a slight preference for working toward modifying the current remission
      criteria by adding patient-reported outcomes (PRO), or by substituting the
      patient's global assessment with 1 or more PRO. CONCLUSION: More evidence on
      measuring patients' perspective on remission in RA is needed before an informed
      decision can be made regarding development or modification of remission
      definitions.

PMID- 28765251
TI  - Severe Infection in Antineutrophil Cytoplasmic Antibody-associated Vasculitis.
AB  - OBJECTIVE: To compare the rate of severe infections after the onset of
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with the
      rate in the background population, and to identify predictors of severe
      infections among patients with AAV. METHODS: The study cohort was 186 patients
      with AAV diagnosed from 1998 to 2010, consisting of all known cases in a defined
      population in southern Sweden. For each patient, 4 age-and sex-matched reference
      subjects were randomly chosen from the background population. Using the Skane
      Healthcare Register, all International Classification of Diseases codes of
      infections assigned from 1998 to 2011 were identified. Severe infections were
      defined as infectious episodes requiring hospitalization. Rate ratios were
      calculated by dividing the rate in AAV by the rate among the reference subjects.
      RESULTS: The rate ratio for all severe infections was 4.53 (95% CI 3.39-6.00).
      The highest rate ratios were found for upper respiratory tract: 8.88 (3.54-25.9),
      Clostridium difficile: 5.35 (1.54-23.8), nonspecific septicemia 4.55 (1.60-13.8),
      and skin 5.35 (1.69-19.8). Of the severe infections, 38.4% occurred within 6
      months of diagnosis, 30.2% from 7-24 months, and 31.4% after 24 months. High
      serum creatinine and older age at diagnosis were associated with severe infection
      (p < 0.001). Of those with severe infection, 46.5% died during followup compared
      to 26% of patients without severe infection (p = 0.004). CONCLUSION: Patients
      with AAV have markedly higher rates of severe infection compared with the
      background population, especially patients with older age and impaired renal
      function. The risk of severe infection is particularly high in the first 6 months
      following the diagnosis of vasculitis.

PMID- 28765252
TI  - Management of Gout in a Hospital Setting: A Lost Opportunity.
AB  - OBJECTIVE: Management of gout is frequently suboptimal. The aim of this study was
      to determine the proportion of patients presenting to Christchurch Hospital for a
      gout flare and to determine whether management for both acute flares and urate
      lowering was in accordance with international recommendations. METHODS: A
      retrospective audit was undertaken of all admissions to Christchurch Hospital
      from June 1, 2013, to May 31, 2014, in which gout was coded as a primary or
      secondary discharge diagnosis. Information including demographics, comorbidities,
      concomitant medications, treatment of acute gout, and urate lowering was
      collected. RESULTS: A total of 235 acute admissions for gout in 216 individuals
      were identified. Eleven individuals had 2 admissions and 4 individuals had 3
      admissions. In 95/235 admissions (40.4%), gout was the primary diagnosis. Gout
      accounted for 95/77,321 (0.12%) of acute admissions. The treatment of acute gout
      was prednisone monotherapy in 170/235 (72.3%) of admissions. Serum urate was
      measured at some point during 123/235 (52.3%) of admissions, with only 19/123
      (15.4%) at target urate level (< 0.36 mmol/l). At 60 of the 235 admissions, urate
      lowering therapy was already being prescribed. Nine out of 175 patients (5.1%)
      not treated with urate-lowering therapy at admission commenced allopurinol and
      32/174 (18.4%) had commencement of urate-lowering therapy recommended in the
      discharge plan. CONCLUSION: Rates of admission for gout are similar to that
      observed in other studies. Failure to initiate, change, or recommend alterations
      in urate-lowering therapy to achieve target urate in people with gout admitted to
      hospital represents a significant lost opportunity to improve longterm gout
      management.

PMID- 28765253
TI  - The SPECTRA Collaboration OMERACT Special Interest Group: Current Research and
      Future Directions.
AB  - OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT)
      has the potential to improve radiographic progression determination in clinical
      trials and longitudinal observational studies. The goal of this work was to
      describe the current state of research presented at Outcome Measures in
      Rheumatology (OMERACT) 2016 and ensuing future directions outlined during
      discussion among attendees. METHODS: At OMERACT 2016, SPECTRA (Study grouP for
      xtrEme-Computed Tomography in Rheumatoid Arthritis) introduced efforts to (1)
      validate the HR-pQCT according to OMERACT guidelines, focusing on rheumatoid
      arthritis (RA), and (2) find alternatives for automated joint space width (JSW)
      analysis. The Special Interest Group (SIG) was presented to patient research
      partners, physicians/researchers, and SIG leaders followed by a 40-min discussion
      on future directions. RESULTS: A consensus definition for RA erosion using HR
      pQCT was demonstrated through a systematic literature review and a Delphi
      exercise. Histopathology and perfusion studies were presented that analyzed the
      true characteristics of cortical breaks in HR-pQCT images, and to provide
      criterion validity. Results indicate that readers were able to discriminate
      between erosion and small vascular channels. Moderate reliability (ICC 0.206
      0.871) of direct erosion size measures was shown, which improved (> 0.9) only
      when experienced readers were considered. Quantification of erosion size was
      presented for scoring, direct measurement, and volumetric approaches, as well as
      a reliability exercise for direct measurement. Three methods for JSW measurement
      were compared, all indicating excellent reproducibility with differences at the
      extremes (i.e., near-zero and joint edge thickness). CONCLUSION: Initial reports
      on HR-pQCT are promising; however, to consider its use in clinical trials and
      longitudinal observational studies, it is imperative to assess the responsiveness
      of erosion measurement quantification.

PMID- 28765254
TI  - Risk of Obstructive Sleep Apnea and Its Association with Cardiovascular and
      Noncardiac Vascular Risk in Patients with Rheumatoid Arthritis: A Population
      based Study.
AB  - OBJECTIVE: To define the incidence of obstructive sleep apnea (OSA) in patients
      with rheumatoid arthritis (RA) and determine whether OSA diagnosis predicts
      future cardiovascular disease (CVD) and noncardiac vascular events. METHODS:
      Medical information pertaining to RA, OSA, CVD, and vascular diagnoses was
      extracted from a comprehensive medical record system for a geographically defined
      population of 813 patients previously diagnosed with RA and 813 age- and sex
      matched comparator subjects. RESULTS: The risk for OSA in persons with RA versus
      comparators was elevated, although not reaching statistical significance (HR
      1.32, 95% CI 0.98-1.77; p = 0.07). Patients with RA were more likely to be
      diagnosed with OSA if they had traditional risk factors for OSA, including male
      sex, current smoking status, hypertension, diabetes, dyslipidemia, and increased
      body mass index. Features of RA disease associated with OSA included large joint
      swelling and joint surgery. Patients with RA with decreased renal function were
      also at higher risk of OSA. The increased risk of overall CVD among patients with
      RA who have OSA was similar to the increased CVD risk associated with OSA in the
      comparator cohort (interaction p = 0.86). OSA diagnosis was associated with an
      increased risk of both CVD (HR 1.9, 95% CI 1.08-3.27), and cerebrovascular
      disease (HR 2.4, 95% CI 1.14-5.26) in patients with RA. CONCLUSION: Patients with
      RA may be at increased risk of OSA secondary to both traditional and RA-related
      risk factors. Diagnosis with OSA predicts future CVD in RA and may provide an
      opportunity for CVD intervention.

PMID- 28765255
TI  - Malignancy in Pediatric-onset Systemic Lupus Erythematosus.
AB  - OBJECTIVE: To determine cancer incidence in a large pediatric-onset systemic
      lupus erythematosus (SLE) population. METHODS: Data were examined from 12
      pediatric SLE registries in North America. Patients were linked to their regional
      cancer registries to detect cancers observed after cohort entry, defined as date
      first seen in the clinic. The expected number of malignancies was obtained by
      multiplying the person-years in the cohort (defined from cohort entry to end of
      followup) by the geographically matched age-, sex-, and calendar year-specific
      cancer rates. The standardized incidence ratio (SIR; ratio of cancers observed to
      expected) was generated, with 95% CI. RESULTS: A total of 1168 patients were
      identified from the registries. The mean age at cohort entry was 13 years (SD
      3.3), and 83.7% of the subjects were female. The mean duration of followup was
      7.6 years, resulting in a total observation period of 8839 years spanning the
      calendar period 1974-2009. During followup, fourteen invasive cancers occurred
      (1.6 cancers per 1000 person-yrs, SIR 4.13, 95% CI 2.26-6.93). Three of these
      were hematologic (all lymphomas), resulting in an SIR for hematologic cancers of
      4.68 (95% CI 0.96-13.67). SIR were increased for both male and female patients,
      and across age groups. CONCLUSION: Although cancer remains a relatively rare
      outcome in pediatric-onset SLE, our data do suggest an increase in cancer for
      patients followed an average of 7.6 years. About one-fifth of the cancers were
      hematologic. Longer followup, and study of drug effects and disease activity, is
      warranted.

PMID- 28765257
TI  - Tenosynovial Giant Cell Tumor: Incidence, Prevalence, Patient Characteristics,
      and Recurrence. A Registry-based Cohort Study in Denmark.
AB  - OBJECTIVE: Tenosynovial giant cell tumor (TGCT) is a rare benign proliferative
      and inflammatory disease arising from synovia of joints, bursae, or tendon
      sheaths. We aimed to estimate incidence rate and prevalence of TGCT in Denmark,
      to describe patient characteristics and treatment modalities among patients with
      TGCT, and to estimate risk of TGCT recurrence. METHODS: Using registry data on
      pathology examinations and inpatient and outpatient hospital diagnoses, we
      identified adult patients with diagnoses of diffuse TGCT (D-TGCT) or localized
      TGCT (L-TGCT) between 1997 and 2012, followed through 2012. We described
      patients' characteristics, treatment modalities, and recurrence. RESULTS: We
      identified 2087 patients with L-TGCT and 574 patients with D-TGCT. Their
      incidence rates per million person-years were 30.3 (95% CI 29.1-31.7) and 8.4
      (95% CI 7.7-9.1), respectively. At the end of 2012, prevalence per 100,000
      persons was 44.3 (95% CI 42.4-46.3) for L-TGCT and 11.5 (95% CI 10.6-12.6) for D
      TGCT. Women made up 61% of the patients with L-TGCT and 51% of the patients with
      D-TGCT. Median age at diagnosis was 47 years. Ten-year risk of recurrence was
      9.8% (95% CI 8.4-11.3%) after L-TGCT and 19.1% (95% CI 15.7-22.7%) after D-TGCT.
      CONCLUSION: This study contributes evidence about epidemiology of TGCT based on
      routinely collected population-based data gathered in a setting of universal
      equal access to healthcare and complete followup.

PMID- 28765256
TI  - Engaging Stakeholders and Promoting Uptake of OMERACT Core Outcome Instrument
      Sets.
AB  - OBJECTIVE: While there has been substantial progress in the development of core
      outcomes sets, the degree to which these are used by researchers is variable. We
      convened a special workshop on knowledge translation at the Outcome Measures in
      Rheumatology (OMERACT) 2016 with 2 main goals. The first focused on the
      development of a formal knowledge translation framework and the second on
      promoting uptake of recommended core outcome domain and instrument sets. METHODS:
      We invited all 189 OMERACT 2016 attendees to the workshop; 86 attended,
      representing patient research partners (n = 15), healthcare providers/clinician
      researchers (n = 52), industry (n = 4), regulatory agencies (n = 4), and OMERACT
      fellows (n = 11). Participants were given an introduction to knowledge
      translation and were asked to propose and discuss recommendations for the OMERACT
      community to (1) strengthen stakeholder involvement in the core outcome
      instrument set development process, and (2) promote uptake of core outcome sets
      with a specific focus on the potential role of post-regulatory decision makers.
      RESULTS: We developed the novel "OMERACT integrated knowledge translation"
      framework, which formalizes OMERACT's knowledge translation strategies. We
      produced strategies to improve stakeholder engagement throughout the process of
      core outcome set development and created a list of creative and innovative ways
      to promote the uptake of OMERACT's core outcome sets. CONCLUSION: The guidance
      provided in this paper is preliminary and is based on the views of the
      participants. Future work will engage OMERACT groups, "post-regulatory decision
      makers," and a broad range of different stakeholders to identify and evaluate the
      most useful methods and processes, and to revise guidance accordingly.

PMID- 28765258
TI  - Persistence of the losing cord blood unit following double cord blood
      transplantation: finding the unseen.

PMID- 28765259
TI  - Glucose but not KCl diminishes submembrane granule turnover in mouse beta-cells.
AB  - KCl depolarization is widely used to mimic the depolarization during glucose
      stimulated insulin secretion. Consequently, the insulin secretion elicited by KCl
      is often regarded as the equivalent of the first phase of glucose-induced insulin
      secretion. Here, the effects of both stimuli were compared by measuring the
      secretion of perifused mouse islets, the cytosolic Ca2+ concentration of single
      beta-cells and the mobility of submembrane insulin granules by TIRF microscopy of
      primary mouse beta-cells. Two cargo-directed granule labels were used namely
      insulin-EGFP and C-peptide-emGFP. The granule behaviour common to both was used
      to compare the effect of sequential stimulation with 40 mM KCl and 30 mM glucose
      and sequential stimulation with the same stimuli in reversed order. At the level
      of the cell secretory response, the sequential pulse protocol showed marked
      differences depending on the order of the two stimuli. KCl produced higher
      maximal secretion rates and diminished the response to the subsequent glucose
      stimulus, whereas glucose enhanced the response to the subsequent KCl stimulus.
      At the level of granule behaviour, a difference developed during the first
      stimulation phase in that the total number of granules, the short-term resident
      granules and the arriving granules, which are all parameters of granule turnover,
      were significantly smaller for glucose than for KCl. These differences at both
      the level of the cell secretory response and granule behaviour in the submembrane
      space are incompatible with identical initial response mechanisms to KCl and
      glucose stimulation.

PMID- 28765260
TI  - Tracing Cellular Origin of Human Exosomes Using Multiplex Proximity Extension
      Assays.

PMID- 28765261
TI  - Burden of child and adolescent obesity on health services in England.
AB  - OBJECTIVE: To assess the numbers of obese children and young people (CYP)
      eligible for assessment and management at each stage of the childhood obesity
      pathway in England. DESIGN: Pathway modelling study, operationalising the UK
      National Institute for Health and Care Excellence guidance on childhood obesity
      management against national survey data. SETTING: Data on CYP aged 2-18 years
      from the Health Survey for England 2006 to 2013. MAIN OUTCOME MEASURES: Clinical
      obesity (body mass index (BMI) >98th centile), extreme obesity (BMI >=99.86th
      centile); family history of cardiovascular disease or type 2 diabetes; obesity
      comorbidities defined as primary care detectable (hypertension, orthopaedic or
      mobility problems, bullying or psychological distress) or secondary care
      detectable (dyslipidaemia, hyperinsulinaemia, high glycated haemoglobin, abnormal
      liver function). RESULTS: 11.2% (1.22 million) of CYP in England were eligible
      for primary care assessment and for community lifestyle modification. 2.6% (n=283
      500) CYP were estimated to be likely to attend primary care. 5.1% (n=556 000)
      were eligible for secondary care referral. Among those aged 13-18 years, 8.2%
      (n=309 000) were eligible for antiobesity drug therapy and 2.4% (90 500) of
      English CYP were eligible for bariatric surgery. CYP from the most deprived
      quintile were 1.5-fold to 3-fold more likely to be eligible for obesity
      management. CONCLUSIONS: There is a mismatch between population burden and
      available data on service use for obesity in CYP in England, particularly among
      deprived young people. There is a need for consistent evidence-based
      commissioning of services across the childhood obesity pathway based on
      population burden.

PMID- 28765262
TI  - Interplay of physiology, social, familial and behavioural adaptation in the long
      term outcome of ARDS.

PMID- 28765265
TI  - Is myometrial inflammation a cause or a consequence of term human labour?
AB  - Myometrial inflammation is thought to have a pivotal role in the onset of term
      and some forms of preterm labour. This is based on the comparison of samples
      taken from women undergoing term elective CS prior to the onset of labour with
      those taken from women in established labour. Consequently, it is not clear
      whether myometrial inflammation is a cause or a consequence of labour. Our
      objective is to test the hypothesis that myometrial inflammation is a consequence
      of the onset of labour. To test this hypothesis, we have obtained myometrial
      samples from women at various stages of pregnancy and spontaneous labour and
      studied the activation of the AP-1 (c-Jun) and NFkappaB (p65) systems, cytokine
      mRNA expression and protein levels and inflammatory cell infiltration and
      activation. We found that the activation of p65 declined from preterm to term not
      in labour samples and thereafter increased in early and established labour.
      Cytokine mRNA expression and protein levels increased in established labour only.
      Using flow cytometry of myometrial tissue, we found that the number of
      neutrophils did increase with the onset of labour, but on tissue section, these
      were seen to be intravascular and not infiltrating into the myometrium. These
      data suggest that myometrial inflammation is a consequence rather than a cause of
      term labour.

PMID- 28765264
TI  - Anti-inflammatory effects of exercise training in adipose tissue do not require
      FGF21.
AB  - Exercise enhances insulin sensitivity; it also improves adipocyte metabolism and
      reduces adipose tissue inflammation through poorly defined mechanisms. Fibroblast
      growth factor 21 (FGF21) is a pleiotropic hormone-like protein whose insulin
      sensitizing properties are predominantly mediated via receptor signaling in
      adipose tissue (AT). Recently, FGF21 has also been demonstrated to have anti
      inflammatory properties. Meanwhile, an association between exercise and increased
      circulating FGF21 levels has been reported in some, but not all studies. Thus,
      the role that FGF21 plays in mediating the positive metabolic effects of exercise
      in AT are unclear. In this study, FGF21-knockout (KO) mice were used to directly
      assess the role of FGF21 in mediating the metabolic and anti-inflammatory effects
      of exercise on white AT (WAT) and brown AT (BAT). Male FGF21KO and wild-type mice
      were provided running wheels or remained sedentary for 8 weeks (n = 9-15/group)
      and compared for adiposity, insulin sensitivity (i.e., HOMA-IR, Adipo-IR) and AT
      inflammation and metabolic function (e.g., mitochondrial enzyme activity, subunit
      content). Adiposity and Adipo-IR were increased in FGF21KO mice and decreased by
      EX. The BAT of FGF21KO animals had reduced mitochondrial content and decreased
      relative mass, both normalized by EX. WAT and BAT inflammation was elevated in
      FGF21KO mice, reduced in both genotypes by EX. EX increased WAT Pgc1alpha gene
      expression, citrate synthase activity, COX I content and total AMPK content in WT
      but not FGF21KO mice. Collectively, these findings reveal a previously
      unappreciated anti-inflammatory role for FGF21 in WAT and BAT, but do not support
      that FGF21 is necessary for EX-mediated anti-inflammatory effects.

PMID- 28765267
TI  - A Chinese Perspective on Receptors and Receptor Regulation.
AB  - A receptor is a protein molecule that receives chemical signals from outside a
      cell, which enables the cell to respond to the signal molecule. Receptors mediate
      numerous important physiologic effects upon binding extracellular agonists.
      However, sustained activation of the receptor may lead to pathologic effects.
      Cells can regulate the number and function of receptors to alter their
      sensitivity to different molecules by a feedback mechanism, such as change in the
      receptor conformation, uncoupling of the receptor effector molecules, receptor
      sequestration, etc. In this special issue, some Chinese scientists were invited
      to contribute impactful discoveries and insightful reviews in the field of
      molecular pharmacology, especially receptor and receptor regulation.

PMID- 28765266
TI  - ADAM12 Is a Novel Regulator of Tumor Angiogenesis via STAT3 Signaling.
AB  - ADAM12, (ADisintegrin and metalloproteinase domain-containing protein 12), is
      upregulated in epithelial cancers and contributes to increased tumor
      proliferation, metastasis, and endocrine resistance. However, its role in tumor
      angiogenesis is unknown. Here, we report that ADAM12 is upregulated in the
      vessels of aggressive breast tumors and exerts key regulatory functions. ADAM12
      significantly increases bFGF-mediated angiogenesis in vivo and ADAM12 levels are
      upregulated in tumors that have undergone a switch to the angiogenic phenotype.
      Importantly, ADAM12-overexpressing breast tumors display a higher microvessel
      density (MVD). Our goal was to identify the mechanisms by which tumor-associated
      ADAM12 promotes angiogenesis. ADAM12 expression in breast tumor cells correlated
      with a significant upregulation of proangiogenic factors such as VEGF and MMP-9
      and downregulation of antiangiogenic factors such as Thrombospondin-1
      (THBS1/TSP1) and Tissue Inhibitor of Metalloproteinases-2 (TIMP-2). Co-culture
      with ADAM12-expressing tumor cells promoted endothelial cell (EC) recruitment and
      capillary tube formation. Conversely, downregulation of endogenous ADAM12 in
      breast cancer cell lines resulted in reduction of pro-angiogenic factors and EC
      recruitment. These ADAM12-mediated effects are driven by the activation of EGFR,
      STAT3 and Akt signaling. Blockade of EGFR/STAT3 or silencing of ADAM12 reversed
      the proangiogenic tumor phenotype, significantly downregulated pro-angiogenic
      mitogens and reduced EC recruitment. In human breast cancer tissues, ADAM12
      expression was significantly positively correlated with pro-angiogenic factors
      including VEGF and MMP-9 but negatively associated with TSP1.Implications: These
      novel findings suggest that ADAM12 regulates EC function and facilitates a
      proangiogenic microenvironment in a STAT3-dependent manner. A combined approach
      of targeting ADAM12 and STAT3 signaling in breast cancer may represent a
      promising strategy to inhibit tumor neovascularization. Mol Cancer Res; 15(11);
      1608-22. (c)2017 AACR.

PMID- 28765268
TI  - The Achilles tendon and the retrocalcaneal bursa: An anatomical and radiological
      study.
AB  - OBJECTIVES: Inflammation of the retrocalcaneal bursa (RB) is a common clinical
      problem, particularly in professional athletes. RB inflammation is often treated
      with corticosteroid injections however a number of reports suggest an increased
      risk of Achilles tendon (AT) rupture. The aim of this cadaveric study was to
      describe the anatomical connections of the RB and to investigate whether it is
      possible for fluid to move from the RB into AT tissue. METHODS: A total of 20
      fresh-frozen AT specimens were used. In ten specimens, ink was injected into the
      RB. The remaining ten specimens were split into two groups to be injected with
      radiological contrast medium into the RB either with or without ultrasonography
      guidance (USG). RESULTS: In specimens injected with ink, diffusion outside the RB
      was observed with staining of the anterior portion of the AT. In eight contrast
      injected specimens (five USG, three non-USG), a similar localised diffusion
      pattern was observed, with the contrast identified superiorly and anteriorly. In
      two contrast-injected specimens (non-USG), the diffusion pattern was more
      extensive. CONCLUSION: This study confirmed the existence of connections between
      the RB and the AT, especially rich in the anteroinferior portion of the tendon,
      which should be considered a weak zone for substances injected into the RB. We
      hypothesise that this part of the AT might be most vulnerable to rupture after
      corticosteroid injections.Cite this article: P. A. Pekala, B. M. Henry, J. R.
      Pekala, K. Piska, K. A. Tomaszewski. The Achilles tendon and the retrocalcaneal
      bursa: An anatomical and radiological study. Bone Joint Res 2017;6:446-451.
      DOI:10.1302/2046-3758.67.BJR-2016-0340.R1.

PMID- 28765270
TI  - Improving hospital death certification in Vietnam: results of a pilot study of
      injury-related fatalities.
AB  - BACKGROUND: Vietnam has prioritised the establishment of a civil registration
      system for deaths but as yet is unable to report accurate national statistics for
      the population of 93.5 million people due to inadequate mortality data. Verbal
      autopsy data suggest that injury is a third leading cause of death (by
      International Statistical Classification of Diseases and Related Health Problems
      10th Revision chapters) in Vietnam, with road traffic injuries in particular a
      significant and increasing challenge. The study aims to present a more accurate
      profile of the number and probable causes of these deaths based on data collected
      hospitals using a version of the WHO death certificate modified for the
      Vietnamese context. METHODS: Death data collected from Viet Duc Surgical and
      Trauma Hospital in Vietnam between 1 March 2013 to 31 March 2015 was analysed to
      explore the number and probable causes of deaths for deaths resulting from an
      injury. RESULTS: A total of 1616 deaths were recorded for Viet Duc Hospital, of
      which 73% (1181/1616) were associated with an injury. Most (83%; n=871/1049)
      injury-related deaths for which immediate cause of death was documented were as a
      result of head/brain injuries. Injury-related deaths were most commonly caused by
      from traffic accidents (72%, 853/1181). The majority of patients suffering injury
      related deaths were discharged home to die (93%, 1097/1181). CONCLUSION: The
      study confirms some findings from previous studies about deaths from injuries,
      while disagreeing with others, highlighting the challenge for Vietnam in
      collecting these data. Gathering detailed death data provides essential evidence
      on which to base decisions about allocation of government funding and policy for
      injury prevention and treatment.

PMID- 28765269
TI  - The efficacy and safety of vertebral fracture prevention therapies in post
      menopausal osteoporosis treatment: Which therapies work best? a network meta
      analysis.
AB  - OBJECTIVES: Osteoporosis has become an increasing concern for older people as it
      may potentially lead to osteoporotic fractures. This study is designed to assess
      the efficacy and safety of ten therapies for post-menopausal women using network
      meta-analysis. METHODS: We conducted a systematic search in several databases,
      including PubMed and Embase. A random-effects model was employed and results were
      assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI).
      Furthermore, with respect to each outcome, each intervention was ranked according
      to the surface under the cumulative ranking curve (SUCRA) value. RESULTS: With
      respect to preventing new vertebral fractures (NVF), all ten drugs outperformed
      placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95%
      CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked
      higher compared with the other drugs. With respect to preventing clinical
      vertebral fractures (CVF), zoledronic acid proved to be the most effective drug
      (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR
      = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for
      adverse events (AE) and severe adverse events (SAE), no significant difference
      was observed. According to SUCRA, etidronate ranked first in preventing CVF;
      parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF.
      Raloxifene was safe with a high rank in preventing AEs and SAEs though performed
      unsatisfactorily in efficacy. CONCLUSIONS: This study suggests that, taking
      efficacy and safety into account, parathyroid hormone and zoledronic acid had the
      highest probability of satisfactory performance in preventing osteoporotic
      fractures.Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The
      efficacy and safety of vertebral fracture prevention therapies in post-menopausal
      osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone
      Joint Res 2017;6:452-463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1.

PMID- 28765271
TI  - SIRT6 regulates metabolic homeostasis in skeletal muscle through activation of
      AMPK.
AB  - Because of the mass and functions in metabolism, skeletal muscle is one of the
      major organs regulating whole body metabolic homeostasis. SIRT6, a histone
      deacetylase, has been shown to regulate metabolism in liver and brain; however,
      its specific role in skeletal muscle is undetermined. In the present study we
      explored physiological function of SIRT6 in muscle. We generated a muscle
      specific SIRT6 knockout mouse model. The mice with SIRT6 deficiency in muscle
      displayed impaired glucose homeostasis and insulin sensitivity, attenuated whole
      body energy expenditure, and weakened exercise performance. Mechanistically,
      deletion of SIRT6 in muscle decreased expression of genes involved in glucose and
      lipid uptake, fatty acid oxidation, and mitochondrial oxidative phosphorylation
      in muscle cells because of the reduced AMP-activated protein kinase (AMPK)
      activity. In contrast, overexpression of SIRT6 in C2C12 myotubes activates AMPK.
      Our results from both gain- and loss-of-function experiments identify SIRT6 as a
      physiological regulator of muscle mitochondrial function. These findings indicate
      that SIRT6 is a potential therapeutic target for treatment of type 2 diabetes
      mellitus.

PMID- 28765272
TI  - "Calories in, calories out" and macronutrient intake: the hope, hype, and science
      of calories.
AB  - One of the central tenets in obesity prevention and management is caloric
      restriction. This perspective presents salient features of how calories and
      energy balance matter, also called the "calories in, calories out" paradigm.
      Determinants of energy balance and relationships to dietary macronutrient content
      are reviewed. The rationale and features of the carbohydrate-insulin hypothesis
      postulate that carbohydrate restriction confers a metabolic advantage. According
      to this model, a large amount of fat intake is enabled without weight gain.
      Evidence concerning this possibility is detailed. The relationship and
      application of the laws of thermodynamics are then clarified with current primary
      research. Strong data indicate that energy balance is not materially changed
      during isocaloric substitution of dietary fats for carbohydrates. Results from a
      number of sources refute both the theory and effectiveness of the carbohydrate
      insulin hypothesis. Instead, risk for obesity is primarily determined by total
      calorie intake.

PMID- 28765274
TI  - When Insulin Therapy Fails: The Impact of SGLT2 Inhibitors in Patients With Type
      2 Diabetes.

PMID- 28765273
TI  - Cross-sex testosterone therapy in ovariectomized mice: addition of low-dose
      estrogen preserves bone architecture.
AB  - Cross-sex hormone therapy (XHT) is widely used by transgender people to alter
      secondary sex characteristics to match their desired gender presentation. Here,
      we investigate the long-term effects of XHT on bone health using a murine model.
      Female mice underwent ovariectomy at either 6 or 10 wk and began weekly
      testosterone or vehicle injections. Dual-energy X-ray absorptiometry (DXA) was
      performed (20 wk) to measure bone mineral density (BMD), and microcomputed
      tomography was performed to compare femoral cortical and trabecular bone
      architecture. The 6-wk testosterone group had comparable BMD with controls by DXA
      but reduced bone volume fraction, trabecular number, and cortical area fraction
      and increased trabecular separation by microcomputed tomography. Ten-week
      ovariectomy/XHT maintained microarchitecture, suggesting that estrogen is
      critical for bone acquisition during adolescence and that late, but not early,
      estrogen loss can be sufficiently replaced by testosterone alone. Given these
      findings, we then compared effects of testosterone with effects of weekly
      estrogen or combined testosterone/low-dose estrogen treatment after a 6-wk
      ovariectomy. Estrogen treatment increased spine BMD and microarchitecture,
      including bone volume fraction, trabecular number, trabecular thickness, and
      connectivity density, and decreased trabecular separation. Combined testosterone
      estrogen therapy caused similar increases in femur and spine BMD and improved
      architecture (increased bone volume fraction, trabecular number, trabecular
      thickness, and connectivity density) to estrogen therapy and were superior
      compared with mice treated with testosterone only. These results demonstrate
      estradiol is critical for bone acquisition and suggest a new cross-sex hormone
      therapy adding estrogens to testosterone treatments with potential future
      clinical implications for treating transgender youth or men with estrogen
      deficiency.

PMID- 28765275
TI  - Proline Accumulation Is Regulated by Transcription Factors Associated with
      Phosphate Starvation.
AB  - Pro accumulation in plants is a well-documented physiological response to osmotic
      stress caused by drought or salinity. In Arabidopsis (Arabidopsis thaliana), the
      stress and ABA-induced Delta1-PYRROLINE-5-CARBOXYLATE SYNTHETASE1 (P5CS1) gene
      was previously shown to control Pro biosynthesis in such adverse conditions. To
      identify regulatory factors that control the transcription of P5CS1, Y1H screens
      were performed with a genomic fragment of P5CS1, containing 1.2-kB promoter and
      0.8-kb transcribed regions. The myeloblastosis (MYB)-type transcription factors
      PHOSPHATE STARVATION RESPONSE1 (PHR1) and PHR1-LIKE1 (PHL1) were identified to
      bind to P5CS1 regulatory sequences in the first intron, which carries a conserved
      PHR1-binding site (P1BS) motif. Binding of PHR1 and PHL1 factors to P1BS was
      confirmed by Y1H, electrophoretic mobility assay and chromatin
      immunoprecipitation. Phosphate starvation led to gradual increase in Pro content
      in wild-type Arabidopsis plants as well as transcriptional activation of P5CS1
      and PRO DEHYDROGENASE2 genes. Induction of P5CS1 transcription and Pro
      accumulation during phosphate deficiency was considerably reduced by phr1 and
      phl1 mutations and was impaired in the ABA-deficient aba2-3 and ABA-insensitive
      abi4-1 mutants. Growth and viability of phr1phl1 double mutant was significantly
      reduced in phosphate-depleted medium, while growth was only marginally affected
      in the aba2-3 mutants, suggesting that ABA is implicated in growth retardation in
      such nutritional stress. Our results reveal a previously unknown link between Pro
      metabolism and phosphate nutrition and show that Pro biosynthesis is target of
      cross talk between ABA signaling and regulation of phosphate homeostasis through
      PHR1- and PHL1-mediated transcriptional activation of the P5CS1 gene.

PMID- 28765276
TI  - Vascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian
      Randomization Study.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) has angiogenic and possibly
      proatherosclerotic properties. Observationally it is positively associated with
      cardiovascular disease, although these observations could be confounded or due to
      reverse causation. We assessed ischemic heart disease (IHD) risk by genetically
      predicted VEGF, ie, using Mendelian randomization. METHODS AND RESULTS: Single
      nucleotide polymorphisms (SNPs) predicting VEGF level, at genome-wide
      significance, were applied to the CARDIoGRAMplusC4D 1000 Genomes-based genome
      wide association study IHD case (n=60 801)-control (n=123 504) study. We obtained
      unconfounded estimates using instrumental variable analysis by combining the Wald
      estimates for each SNP using inverse variance weighting and Mendelian
      randomization-Egger regression. Based on 9 SNPs independently predicting VEGF
      (rs1740073 [C6orf223], rs2375981 [KCNV2], rs2639990 [ZADH2], rs4782371 [ZFPM1],
      rs6921438 [LOC100132354], rs7043199 [VLDLR-AS1], rs10761741 [JMJD1C], rs6993770
      [ZFPM2], and rs114694170 [MEF2C]), VEGF was unrelated to IHD (odds ratio 0.99 per
      log-transformed pg/mL, 95%CI 0.96-1.02) using inverse variance weighting.
      However, Mendelian randomization-Egger regression suggested an inverse relation
      of VEGF with IHD (odds ratio 0.95, 95%CI 0.91-0.99), although the association was
      not evident after excluding the lead SNP (rs6921438) or additionally excluding
      the pleiotropic SNP (rs6993770). CONCLUSIONS: Our study does not provide strong
      evidence for a positive effect of VEGF on IHD but does not rule out the
      possibility that some specific types of VEGF, for which genetic predictors have
      not yet been identified, might play a role.

PMID- 28765277
TI  - Blood Pressure in 6-Year-Old Children Born Extremely Preterm.
AB  - BACKGROUND: Advances in perinatal medicine have increased infant survival after
      very preterm birth. Although this progress is welcome, there is increasing
      concern that preterm birth is an emerging risk factor for hypertension at young
      age, with implications for the lifetime risk of cardiovascular disease. METHODS
      AND RESULTS: We measured casual blood pressures (BPs) in a population-based
      cohort of 6-year-old survivors of extremely preterm birth (<27 gestational weeks;
      n=171) and in age- and sex-matched controls born at term (n=172). Measured BP did
      not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD
      higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in
      children born extremely preterm than in controls. Among children born extremely
      preterm, shorter gestation, higher body mass index, and higher heart rate at
      follow-up were all independently associated with higher BP at 6 years of age,
      whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal
      corticosteroid therapy were not. In multivariate regression analyses, systolic BP
      decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week
      longer gestation. CONCLUSIONS: Six-year-old children born extremely preterm have
      normal but slightly higher BP than their peers born at term. Although this
      finding is reassuring for children born preterm and their families, follow-up at
      older age is warranted.

PMID- 28765278
TI  - The peroxisomal matrix protein translocon is a large cavity-forming protein
      assembly into which PEX5 protein enters to release its cargo.
AB  - A remarkable property of the machinery for import of peroxisomal matrix proteins
      is that it can accept already folded proteins as substrates. This import involves
      binding of newly synthesized proteins by cytosolic peroxisomal biogenesis factor
      5 (PEX5) followed by insertion of the PEX5-cargo complex into the peroxisomal
      membrane at the docking/translocation module (DTM). However, how these processes
      occur remains largely unknown. Here, we used truncated PEX5 molecules to probe
      the DTM architecture. We found that the DTM can accommodate a larger number of
      truncated PEX5 molecules comprising amino acid residues 1-197 than full-length
      PEX5 molecules. A shorter PEX5 version (PEX5(1-125)) still interacted correctly
      with the DTM; however, this species was largely accessible to exogenously added
      proteinase K, suggesting that this protease can access the DTM occupied by a
      small PEX5 protein. Interestingly, the PEX5(1-125)-DTM interaction was inhibited
      by a polypeptide comprising PEX5 residues 138-639. Apparently, the DTM can
      recruit soluble PEX5 through interactions with different PEX5 domains, suggesting
      that the PEX5-DTM interactions are to some degree fuzzy. Finally, we found that
      the interaction between PEX5 and PEX14, a major DTM component, is stable at pH
      11.5. Thus, there is no reason to assume that the hitherto intriguing resistance
      of DTM-bound PEX5 to alkaline extraction reflects its direct contact with the
      peroxisomal lipid bilayer. Collectively, these results suggest that the DTM is
      best described as a large cavity-forming protein assembly into which cytosolic
      PEX5 can enter to release its cargo.

PMID- 28765279
TI  - The long noncoding RNA HULC promotes liver cancer by increasing the expression of
      the HMGA2 oncogene via sequestration of the microRNA-186.
AB  - The long noncoding RNA highly up-regulated in liver cancer (HULC) is aberrantly
      elevated in hepatocellular carcinoma (HCC), and this up-regulation is crucial for
      HCC pathogenesis. However, the underlying mechanism in HULC up-regulation is
      poorly understood. We hypothesized that HULC might modulate the oncogene high
      mobility group A2 (HMGA2) to promote hepatocarcinogenesis. Quantitative real-time
      PCR analysis showed that the expression levels of HULC were positively correlated
      with those of HMGA2 in clinical HCC tissues. Interestingly, we also observed that
      HULC could up-regulate HMGA2 in HCC cells. Mechanistically, we found that the
      microRNA-186 inhibited HMGA2 expression by targeting the 3'-untranslated region
      (3'-UTR) of HMGA2 mRNA. Strikingly, HULC acted as a competing noncoding RNA to
      sequester miR-186 and thereby relieved miR-186-mediated HMGA2 repression.
      Functionally, HMGA2 knockdown decreased the HULC-enhanced growth of HCC cells
      both in vitro and in vivo We conclude that the long noncoding RNA HULC increases
      HMGA2 expression by sequestering miR-186 post-transcriptionally and thereby
      promotes liver cancer growth, providing new insights into the mechanism by which
      HULC enhances hepatocarcinogenesis.

PMID- 28765280
TI  - The exocyst subunit Sec3 is regulated by a protein quality control pathway.
AB  - Exocytosis involves fusion of secretory vesicles with the plasma membrane,
      thereby delivering membrane proteins to the cell surface and releasing material
      into the extracellular space. The tethering of the secretory vesicles before
      membrane fusion is mediated by the exocyst, an essential phylogenetically
      conserved octameric protein complex. Exocyst biogenesis is regulated by several
      processes, but the mechanisms by which the exocyst is degraded are unknown. Here,
      to unravel the components of the exocyst degradation pathway, we screened for
      extragenic suppressors of a temperature-sensitive fission yeast strain mutated in
      the exocyst subunit Sec3 (sec3-913). One of the suppressing DNAs encoded a
      truncated dominant-negative variant of the 26S proteasome subunit, Rpt2,
      indicating that exocyst degradation is controlled by the ubiquitin-proteasome
      system. The temperature-dependent growth defect of the sec3-913 strain was gene
      dosage-dependent and suppressed by blocking the proteasome, Hsp70-type molecular
      chaperones, the Pib1 E3 ubiquitin-protein ligase, and the deubiquitylating enzyme
      Ubp3. Moreover, defects in cell septation, exocytosis, and endocytosis in sec3
      mutant strains were similarly alleviated by mutation of components in this
      pathway. We also found that, particularly under stress conditions, wild-type Sec3
      degradation is regulated by Pib1 and the 26S proteasome. In conclusion, our
      results suggest that a cytosolic protein quality control pathway monitors folding
      and proteasome-dependent turnover of an exocyst subunit and, thereby, controls
      exocytosis in fission yeast.

PMID- 28765281
TI  - p38 MAPK inhibits nonsense-mediated RNA decay in response to persistent DNA
      damage in noncycling cells.
AB  - Persistent DNA damage induces profound alterations in gene expression that, in
      turn, influence tissue homeostasis, tumorigenesis, and cancer treatment outcome.
      However, the underlying mechanism for gene expression reprogramming induced by
      persistent DNA damage remains poorly understood. Here, using a highly effective
      bioluminescence-based reporter system and other tools, we report that persistent
      DNA damage inhibits nonsense-mediated RNA decay (NMD), an RNA surveillance and
      gene-regulatory pathway, in noncycling cells. NMD suppression by persistent DNA
      damage required the activity of the p38alpha MAPK. Activating transcription
      factor 3 (ATF3), an NMD target and a key stress-inducible transcription factor,
      was stabilized in a p38alpha- and NMD-dependent manner following persistent DNA
      damage. Our results reveal a novel p38alpha-dependent pathway that regulates NMD
      activity in response to persistent DNA damage, which, in turn, controls ATF3
      expression in affected cells.

PMID- 28765282
TI  - The drug transporter OAT3 (SLC22A8) and endogenous metabolite communication via
      the gut-liver-kidney axis.
AB  - The organic anion transporters OAT1 (SLC22A6) and OAT3 (SLC22A8) have similar
      substrate specificity for drugs, but it is far from clear whether this holds for
      endogenous substrates. By analysis of more than 600 metabolites in the Oat3KO
      (Oat3 knockout) by LC/MS, we demonstrate OAT3 involvement in the movement of gut
      microbiome products, key metabolites, and signaling molecules, including those
      flowing through the gut-liver-kidney axis. Major pathways affected included those
      involved in metabolism of bile acids, flavonoids, nutrients, amino acids
      (including tryptophan-derivatives that are uremic toxins), and lipids. OAT3 is
      also critical in elimination of liver-derived phase II metabolites, particularly
      those undergoing glucuronidation. Analysis of physicochemical features revealed
      nine distinct metabolite groups; at least one member of most clusters has been
      previously validated in transport assays. In contrast to drugs interacting with
      the OATs, endogenous metabolites accumulating in the Oat1KO (Oat1 knockout)
      versus Oat3KO have distinct differences in their physicochemical properties; they
      are very different in size, number of rings, hydrophobicity, and molecular
      complexity. Consistent with the Remote Sensing and Signaling Hypothesis, the data
      support the importance of the OAT transporters in inter-organ and inter
      organismal remote communication via transporter-mediated movement of key
      metabolites and signaling molecules (e.g. gut microbiome-to-intestine-to-blood-to
      liver-to-kidney-to-urine). We discuss the possibility of an intimate connection
      between OATs and metabolite sensing and signaling pathways (e.g. bile acids).
      Furthermore, the metabolomics and pathway analysis support the view that OAT1
      plays a greater role in kidney proximal tubule metabolism and OAT3 appears
      relatively more important in systemic metabolism, modulating levels of
      metabolites flowing through intestine, liver, and kidney.

PMID- 28765283
TI  - Heme and nitric oxide binding by the transcriptional regulator DnrF from the
      marine bacterium Dinoroseobacter shibae increases napD promoter affinity.
AB  - Under oxygen-limiting conditions, the marine bacterium Dinoroseobacter shibae
      DFL12T generates energy via denitrification, a respiratory process in which
      nitric oxide (NO) is an intermediate. Accumulation of NO may cause cytotoxic
      effects. The response to this nitrosative (NO-triggered) stress is controlled by
      the Crp/Fnr-type transcriptional regulator DnrF. We analyzed the response to NO
      and the mechanism of NO sensing by the DnrF regulator. Using reporter gene
      fusions and transcriptomics, here we report that DnrF selectively repressed
      nitrate reductase (nap) genes, preventing further NO formation. In addition, DnrF
      induced the expression of the NO reductase genes (norCB), which promote NO
      consumption. We used UV-visible and EPR spectroscopy to characterize heme binding
      to DnrF and subsequent NO coordination. DnrF detects NO via its bound heme
      cofactor. We found that the dimeric DnrF bound one molecule of heme per subunit.
      Purified recombinant apo-DnrF bound its target promoter sequences (napD, nosR2,
      norC, hemA, and dnrE) in electromobility shift assays, and we identified a
      specific palindromic DNA-binding site 5'-TTGATN4ATCAA-3' in these target
      sequences via mutagenesis studies. Most importantly, successive addition of heme
      as well as heme and NO to purified recombinant apo-DnrF protein increased
      affinity of the holo-DnrF for its specific binding motif in the napD promoter. On
      the basis of these results, we propose a model for the DnrF-mediated NO stress
      response of this marine bacterium.

PMID- 28765284
TI  - Structural basis of autoinhibition and activation of the DNA-targeting ADP
      ribosyltransferase pierisin-1.
AB  - ADP-ribosyltransferases transfer the ADP-ribose moiety of betaNAD+ to an acceptor
      molecule, usually a protein that modulates the function of the acceptor. Pierisin
      1 is an ADP-ribosyltransferase from the cabbage butterfly Pieris rapae and is
      composed of N-terminal catalytic and C-terminal ricin B-like domains. Curiously,
      it ADP-ribosylates the DNA duplex, resulting in apoptosis of various cancer
      cells, which has raised interest in pierisin-1 as an anti-cancer agent. However,
      both the structure and the mechanism of DNA ADP-ribosylation are unclear. Here,
      we report the crystal structures of the N-terminal catalytic domain of pierisin
      1, its complex with betaNAD+, and the catalytic domain with the linker connecting
      it to the ricin B-like domains. We found that the catalytic domain possesses a
      defined, positively charged region on the molecular surface but that its overall
      structure is otherwise similar to those of protein-targeting ADP
      ribosyltransferases. Electrophoretic mobility shift assays and site-directed
      mutagenesis indicated that pierisin-1 binds double-stranded but not single
      stranded DNA and that Lys122, Lys123, and Lys124, which are found in a loop, and
      Arg181 and Arg187, located in a basic cleft near the loop, are required for DNA
      binding. Furthermore, the structure of the catalytic domain with the linker
      revealed an autoinhibitory mechanism in which the linker occupies and blocks both
      the betaNAD+- and DNA-binding sites, suggesting that proteolytic cleavage to
      remove the linker is necessary for enzyme catalysis. Our study provides a
      structural basis for the DNA-acceptor specificity of pierisin-1 and reveals that
      a self-regulatory mechanism is required for its activity.

PMID- 28765285
TI  - Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the
      General Population: The AGES-Reykjavik Study (Age Gene/Environment Susceptibility
      Reykjavik Study).
AB  - BACKGROUND AND PURPOSE: The differentiation of brain infarcts by region is
      important because their cause and clinical implications may differ. Information
      on the incidence of these lesions and association with cognition and dementia
      from longitudinal population studies is scarce. We investigated the incidence of
      infarcts in cortical, subcortical, cerebellar, and overall brain regions and how
      prevalent and incident infarcts associate with cognitive change and incident
      dementia. METHODS: Participants (n=2612, 41% men, mean age 74.6+/-4.8) underwent
      brain magnetic resonance imaging for the assessment of infarcts and cognitive
      testing at baseline and on average 5.2 years later. Incident dementia was
      assessed according to the international guidelines. RESULTS: Twenty-one percent
      of the study participants developed new infarcts. The risk of incident infarcts
      in men was higher than the risk in women (1.8; 95% confidence interval, 1.5-2.3).
      Persons with both incident and prevalent infarcts showed steeper cognitive
      decline and had almost double relative risk of incident dementia (1.7; 95%
      confidence interval, 1.3-2.2) compared with those without infarcts. Persons with
      new subcortical infarcts had the highest risk of incident dementia compared with
      those without infarcts (2.6; 95% confidence interval, 1.9-3.4). CONCLUSIONS: Men
      are at greater risk of developing incident brain infarcts than women. Persons
      with incident brain infarcts decline faster in cognition and have an increased
      risk of dementia compared with those free of infarcts. Incident subcortical
      infarcts contribute more than cortical and cerebellar infarcts to incident
      dementia which may indicate that infarcts of small vessel disease origin
      contribute more to the development of dementia than infarcts of embolic origin in
      larger vessels.

PMID- 28765286
TI  - Long-Delay Arterial Spin Labeling Provides More Accurate Cerebral Blood Flow
      Measurements in Moyamoya Patients: A Simultaneous Positron Emission
      Tomography/MRI Study.
AB  - BACKGROUND AND PURPOSE: Arterial spin labeling (ASL) MRI is a promising,
      noninvasive technique to image cerebral blood flow (CBF) but is difficult to use
      in cerebrovascular patients with abnormal, long arterial transit times through
      collateral pathways. To be clinically adopted, ASL must first be optimized and
      validated against a reference standard in these challenging patient cases.
      METHODS: We compared standard-delay ASL (post-label delay=2.025 seconds),
      multidelay ASL (post-label delay=0.7-3.0 seconds), and long-label long-delay ASL
      acquisitions (post-label delay=4.0 seconds) against simultaneous [15O]-positron
      emission tomography (PET) CBF maps in 15 Moyamoya patients on a hybrid PET/MRI
      scanner. Dynamic susceptibility contrast was performed in each patient to
      identify areas of mild, moderate, and severe time-to-maximum (Tmax) delays.
      Relative CBF measurements by each ASL scan in 20 cortical regions were compared
      with the PET reference standard, and correlations were calculated for areas with
      moderate and severe Tmax delays. RESULTS: Standard-delay ASL underestimated
      relative CBF by 20% in areas of severe Tmax delays, particularly in anterior and
      middle territories commonly affected by Moyamoya disease (P<0.001). Arterial
      transit times correction by multidelay acquisitions led to improved consistency
      with PET, but still underestimated CBF in the presence of long transit delays
      (P=0.02). Long-label long-delay ASL scans showed the strongest correlation
      relative to PET, and there was no difference in mean relative CBF between the
      modalities, even in areas of severe delays. CONCLUSIONS: Post-label delay times
      of >=4 seconds are needed and may be combined with multidelay strategies for
      robust ASL assessment of CBF in Moyamoya disease.

PMID- 28765287
TI  - Genetic Inhibition of Receptor Interacting Protein Kinase-1 Reduces Cell Death
      and Improves Functional Outcome After Intracerebral Hemorrhage in Mice.
AB  - BACKGROUND AND PURPOSE: Recent studies using cultured cells and rodent
      intracerebral hemorrhage (ICH) models have implicated RIPK1 (receptor interacting
      protein kinase-1) as a driver of programmed necrosis and secondary injury based
      on use of chemical inhibitors. However, these inhibitors have off-target effects
      and cannot be used alone to prove a role for RIPK1. The aim of the current study
      was to examine the effect of genetic inhibition of the kinase domain of RIPK1 in
      a mouse ICH model. METHODS: We subjected 2 lines of mice with RIPK1 point
      mutations of the kinase domain (K45A and D138N), rendering them kinase inactive,
      to autologous blood ICH and measured acute cell death and functional outcome.
      RESULTS: Compared with wild-type controls, RIPK1K45A/K45A and RIPK1D138N/D138N
      had significantly less cells with plasmalemma permeability, less acute neuronal
      cell death, less weight loss and more rapid weight gain to baseline, and improved
      performance in a Morris water maze paradigm after autologous blood ICH. In
      addition, mice systemically administered GSK'963, a potent, specific, brain
      penetrant small molecule RIPK1 inhibitor, had reduced acute neuronal death at 24
      hours after ICH. CONCLUSIONS: The data show that the kinase domain of RIPK1 is a
      disease driver of ICH, mediating both acute cell death and functional outcome,
      and support development of RIPK1 inhibitors as therapeutic agents for human ICH.

PMID- 28765288
TI  - Association of Computed Tomography Ischemic Lesion Location With Functional
      Outcome in Acute Large Vessel Occlusion Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Ischemic lesion volume (ILV) assessed by follow-up
      noncontrast computed tomography correlates only moderately with clinical end
      points, such as the modified Rankin Scale (mRS). We hypothesized that the
      association between follow-up noncontrast computed tomography ILV and outcome as
      assessed with mRS 3 months after stroke is strengthened when taking the mRS
      relevance of the infarct location into account. METHODS: An anatomic atlas with
      66 areas was registered to the follow-up noncontrast computed tomographic images
      of 254 patients from the MR CLEAN trial (Multicenter Randomized Clinical Trial of
      Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). The anatomic
      brain areas were divided into brain areas of high, moderate, and low mRS
      relevance as reported in the literature. Based on this distinction, the ILV in
      brain areas of high, moderate, and low mRS relevance was assessed for each
      patient. Binary and ordinal logistic regression analyses with and without
      adjustment for known confounders were performed to assess the association between
      the ILVs of different mRS relevance and outcome. RESULTS: The odds for a worse
      outcome (higher mRS) were markedly higher given an increase of ILV in brain areas
      of high mRS relevance (odds ratio, 1.42; 95% confidence interval, 1.31-1.55 per
      10 mL) compared with an increase in total ILV (odds ratios, 1.16; 95% confidence
      interval, 1.12-1.19 per 10 mL). Regression models using ILV in brain areas of
      high mRS relevance instead of total ILV showed a higher quality. CONCLUSIONS: The
      association between follow-up noncontrast computed tomography ILV and outcome as
      assessed with mRS 3 months after stroke is strengthened by accounting for the mRS
      relevance of the affected brain areas. Future prediction models should account
      for the ILV in brain areas of high mRS relevance.

PMID- 28765290
TI  - Corrigendum: TRUB1 is the predominant pseudouridine synthase acting on mammalian
      mRNA via a predictable and conserved code.

PMID- 28765289
TI  - Vascular Risk Factor Profiles Differ Between Magnetic Resonance Imaging-Defined
      Subtypes of Younger-Onset Lacunar Stroke.
AB  - BACKGROUND AND PURPOSE: Differing associations of vascular risk factors with
      lacunar infarct have been reported, which is likely because of diagnostic
      differences and possible heterogeneity in the pathogenesis underlying lacunar
      infarction. In a large magnetic resonance imaging-verified cohort of lacunar
      infarct patients, we investigated the risk factor profile of lacunar infarction
      and magnetic resonance imaging characteristics. METHODS: One thousand twenty
      three patients with lacunar infarction (mean age, 56.7; SD, 8.5) were recruited
      from 72 stroke centers throughout the United Kingdom as part of the UK Young
      Lacunar Stroke DNA Study. Risk factor profiles were compared with 1961 stroke
      free population controls with similar age. Furthermore, we tested risk factor
      profiles of lacunar stroke patients for association with the presence of multiple
      lacunar infarcts, white matter hyperintensities (WMH), and location of the acute
      lacunar infarct. RESULTS: Hypertension (odds ratio [OR], 2.21; 95% confidence
      interval [CI], 1.85-2.64), diabetes mellitus (OR, 2.10; 95% CI, 1.61-2.73),
      hyperlipidemia (OR, 1.74; 95% CI, 1.46-2.07), and smoking (OR, 1.65; 95% CI, 1.39
      1.96) were independently associated in lacunar infarct patients compared with
      healthy controls. Patients with multiple lacunar infarcts were more likely to be
      men (OR, 2.53; 95% CI, 1.81-3.53) and have hypertension (OR, 1.54; 95% CI, 1.12
      2.04) compared with patients with a single lacunar infarct, independent of other
      vascular risk factors. The presence of moderate-to-severe WMH versus no or mild
      WMH was independently associated with increased age (OR, 1.54; 95% CI, 1.12
      2.04), hypertension (OR, 2.06; 95% CI, 1.44-2.95), and impaired renal function
      (OR, 0.90; 95% CI, 0.82-0.98). CONCLUSIONS: In this magnetic resonance imaging
      verified lacunar stroke population, we identified a distinct risk factor profile
      in the group as a whole. However, there were differing risk factor profiles
      according to the presence of multiple lacunar infarcts and confluent WMH. The
      association of hypertension, smoking, and renal impairment with the presence of
      multiple lacunar infarcts and confluent WMH might reflect a diffuse small vessel
      arteriopathy.

PMID- 28765292
TI  - Isolation and Laboratory Domestication of Natural Yeast Strains.
AB  - The process from yeast isolation to their use in laboratory experiments is
      lengthy. Historically, Saccharomyces strains were easily obtained by sampling
      alcoholic fermentation processes or other substrates associated with human
      activity in which Saccharomyces was heavily enriched. In contrast, wild
      Saccharomyces yeasts are found in complex microbial communities and small
      population sizes, making isolation challenging. We have overcome this problem by
      enriching yeast on media favoring the growth of Saccharomyces over other
      microorganisms. The isolation process is usually followed by molecular
      characterization that allows the strain identification. Finally, yeast isolated
      from domestic or wild environments need to be genetically manipulated before they
      can be used in laboratory experiments.

PMID- 28765293
TI  - Mapping Quantitative Trait Loci in Yeast.
AB  - Natural Saccharomyces strains isolated from the wild differ quantitatively in
      molecular and organismal phenotypes. Quantitative trait loci (QTL) mapping is a
      powerful approach for identifying sequence variants that alter gene function. In
      yeast, QTL mapping has been used in designed crosses to map functional
      polymorphisms. This approach, outlined here, is often the first step in
      understanding the molecular basis of quantitative traits. New large-scale
      sequencing surveys have the potential to directly associate genotypes with
      organismal phenotypes, providing a broader catalog of causative genetic variants.
      Additional analysis of intermediate phenotypes (e.g., RNA, protein, or metabolite
      levels) can produce a multilayered and integrated view of individual variation,
      producing a high-resolution view of the genotype-phenotype map.

PMID- 28765294
TI  - Yeast Reciprocal Hemizygosity to Confirm the Causality of a Quantitative Trait
      Loci-Associated Gene.
AB  - Pinpointing causal alleles within a quantitative trait loci region is a key
      challenge when dissecting the genetic basis of natural variation. In yeast,
      homing in on culprit genes is often achieved using engineered reciprocal
      hemizygotes as outlined here. Based on prior information on gene-trait
      associations, candidate genes are identified. In haploid versions of both founder
      strains, a candidate gene is then deleted. Gene knockouts are independently mated
      to a wild-type version of the other strain, such that two diploid hybrid strains
      are obtained. These strains are identical with regard to the nuclear genome,
      except for that they are hemizygotic at the locus of interest and contain
      different alleles of the candidate gene. If correctly measured, a trait
      difference between these reciprocal hemizygotes can confidently be ascribed to
      allelic variation at the target locus.

PMID- 28765295
TI  - Mating-Type Determination in Schizosaccharomyces pombe.
AB  - Here we describe how mating-type tests are conducted in Schizosaccharomyces pombe
      Two methods can be employed: matings with h- and h+ tester strains and polymerase
      chain reaction (PCR) for mat1 content.

PMID- 28765296
TI  - Ethyl Methanesulfonate Mutagenesis in Schizosaccharomyces pombe.
AB  - Here we provide an ethyl methanesulfonate (EMS) mutagenesis protocol for
      Schizosaccharomyces pombe cells.

PMID- 28765297
TI  - Precipitation of DNA with Isopropanol.
AB  - DNA is less soluble in solutions containing isopropanol than in solutions
      containing ethanol. In contrast to precipitation with ethanol, which requires 2-3
      volumes of alcohol, precipitation with isopropanol is performed with 0.6-0.7
      volume of alcohol. Isopropanol is often the better choice when precipitating DNA
      from large volumes of solution. Precipitation with isopropanol, described here,
      is performed at room temperature to lessen the risk that solutes like sucrose or
      sodium chloride will be coprecipitated with the DNA.

PMID- 28765298
TI  - Creation of Recombinant Antibodies: Using Degenerate Oligonucleotides to Amplify
      Heavy- and Light-Chain Sequences.
AB  - Recombinant antibodies can be modified to suit the application: Changes in
      isotype, format (e.g., scFv, Fab, bispecific antibodies), and specificity can be
      made once the heavy- and light-chain sequences are available. However, Ig gene
      families are large and the variable region gene segments are, indeed, variable,
      precluding the use of polymerase chain reaction (PCR) with two simple primers to
      amplify the heavy and light chain gene segments. A wide variety of approaches
      have been taken to obviate the complexity of the variable region gene segments,
      including using "universal" or degenerate primers. In this method, mRNA is
      obtained from B cells as a source of heavy- and light-chain sequences. cDNA is
      prepared using purified mRNA and either oligo(dT) or a C-region 3' primer. The
      cDNA negative strand is complementary to the coding sequence of the heavy or
      light chain. This approach can aid in the design of a variable region primer or
      in selection of the appropriate degenerate primer for a specific variable gene
      subfamily.

PMID- 28765299
TI  - Creation of Recombinant Antibodies: Using 5'-RACE to Amplify Immunoglobulin
      Sequences.
AB  - Modern molecular biology techniques have been applied to the production of
      therapeutic antibodies. Nonetheless, recombinant antibodies remain the exception
      rather than the rule for the antibodies used in most research and diagnostic
      applications. The lack of penetration of recombinant antibodies into the research
      arena can be attributed largely to the fact that the Ig gene families are large
      and the variable region gene segments are, indeed, variable, precluding the use
      of polymerase chain reaction (PCR) with two simple primers to amplify the heavy
      and light chain gene segments. Because of the complexity of the V gene family and
      the number of possible sequences for amplification, there may be a distinct
      advantage to using a PCR method that does not require a specific 5' primer to
      amplify the gene segment. 5'-RACE is just such a method. In the original 5'-RACE
      method, mRNA served as a template for cDNA synthesis using either oligo(dT)
      priming or a gene-specific primer. Terminal deoxynucleotide transferase (TdT) was
      used to tail the first strand with a region of known sequence, such as poly(A).
      Once tailed, the second strand can be amplified using poly(T). This 5'-RACE
      protocol uses the TdT activity of reverse transcriptase, which allows
      nontemplated addition of nucleotides to the end of the nascently made cDNA first
      strand.

PMID- 28765300
TI  - Pronuclear Transplantation in the Mouse Embryo.
AB  - This protocol describes an example of complete zygote enucleation and
      transplantation of male and female pronuclei; however, single pronuclei can also
      be removed and transplanted. In this method, pronuclei are removed without
      penetrating the plasma membrane of the zygote. Instead, they are withdrawn
      individually or together into a membrane-bound karyoplast that can then be fused
      with a recipient enucleated zygote using inactivated Sendai virus or
      electrofusion. Preincubation of the embryos in the presence of the cytoskeletal
      inhibitors cytochalasin B and colcemid is critical for the survival of the
      embryos during this microsurgical procedure. The protocol is divided into five
      parts: (1) isolating embryos, (2) making an enucleation/injection pipette, (3)
      enucleating a zygote, (4) preparing inactivated Sendai virus, and (5) introducing
      pronuclei into enucleated zygotes.

PMID- 28765301
TI  - Cloning Mice.
AB  - Viable and fertile mice can be generated by somatic nuclear transfer into
      enucleated oocytes, presumably because the transplanted somatic cell genome
      becomes reprogrammed by factors in the oocyte. The first somatic cloned offspring
      of mice were obtained by directly injecting donor nuclei into recipient
      enucleated oocytes. When this method is used (the so-called Honolulu method of
      somatic cell nuclear transfer [SCNT]), the donor nuclei readily and completely
      condense within the enucleated metaphase II-arrested oocytes, which contain high
      levels of M-phase-promoting factor (MPF). It is believed that the condensation of
      the donor chromosomes promotes complete reprogramming of the donor genome within
      the mouse oocytes. Another key to the success of mouse cloning is the use of
      blunt micropipettes attached to a piezo impact-driving micromanipulation device.
      This system saves a significant amount of time during the micromanipulation of
      oocytes and thus minimizes the loss of oocyte viability in vitro. For example, a
      group of 20 oocytes can be enucleated within 10 min by an experienced operator.
      This protocol is composed of seven parts: (1) preparing micropipettes, (2)
      setting up the enucleation and injection micropipettes, (3) collecting and
      enucleating oocytes, (4) preparing nucleus donor cells, (5) injecting donor
      nuclei, (6) activating embryos and culturing, and (7) transferring cloned
      embryos.

PMID- 28765302
TI  - Budding Yeast Strains and Genotype-Phenotype Mapping.
AB  - A small number of well-studied laboratory strains of Saccharomyces cerevisiae,
      mostly derived from S288C, are used in yeast research. Although powerful, studies
      for understanding S288C do not always capture the phenotypic essence or the
      genetic complexity of S. cerevisiae biology. This is particularly problematic for
      multilocus phenotypes identified in laboratory strains because these loci have
      never been jointly exposed to natural selection and the corresponding phenotypes
      do not represent optimization for any particular purpose or environment.
      Isolation and sequencing of new natural yeast strains also reveal that the total
      sequence diversity of the S. cerevisiae global population is poorly sampled in
      common laboratory strains. Here we discuss methodologies required for using the
      natural genetic variation in yeast to complete a genotype-phenotype map.

PMID- 28765303
TI  - Genetic Analysis of Schizosaccharomyces pombe.
AB  - In this introduction we discuss some basic genetic tools and techniques that are
      used with the fission yeast Schizosaccharomyces pombe Genes commonly used for
      selection or as reporters are discussed, with an emphasis on genes that permit
      counterselection, intragenic complementation, or colony-color assays. S. pombe is
      most stable as a haploid organism. We describe its mating-type system, how to
      perform genetic crosses and methods for selecting and propagating diploids. We
      discuss the relative merits of tetrad dissection and random spore preparation in
      strain construction and genetic analyses. Finally, we present several types of
      mutant screens, with an evaluation of their respective strengths and limitations
      in the light of emerging technologies such as next-generation sequencing.

PMID- 28765304
TI  - Leveraging psychiatric and medical genetics to understand comorbid depression and
      obesity.
AB  - Precision medicine in psychiatry is on the rise, and depression and obesity - two
      highly prevalent, comorbid and well-characterised phenotypes - are optimal
      targets for the approach. Add the bedrock susceptibility gene, FTO, and Riviera
      et al have identified a constellation of factors that could enhance clinical
      treatment of both disorders.

PMID- 28765305
TI  - Sexual orientation and suicidal behaviour in young people.
AB  - Lesbian, gay, and bisexual (LGB) young people have been found to be at greater
      risk of suicidal behaviour. National prevention strategies have identified the
      need to reduce suicide risk in this population. However, research on specific
      risk factors for LGB young people that might inform suicide prevention programmes
      are at an early stage of development.

PMID- 28765306
TI  - The Psychopathology of Everyday Life, Sigmund Freud - reflection.

PMID- 28765307
TI  - Noise in her Mind - poems by doctors.

PMID- 28765308
TI  - Psychosocial intervention for negative symptoms: a note on meta-analyses.

PMID- 28765309
TI  - Authors' reply.

PMID- 28765310
TI  - The clinical utility of the ADI-R and ADOS in diagnosing autism.

PMID- 28765311
TI  - Author's reply.

PMID- 28765312
TI  - The evidence base and readability of Freeman et al on virtual reality for
      treating delusions.

PMID- 28765313
TI  - Community treatment orders and capacity to consent.

PMID- 28765315
TI  - Correction.

PMID- 28765314
TI  - Authors' reply.

PMID- 28765320
TI  - Corticostriatal signatures of schadenfreude: evidence from Huntington's disease.
AB  - Schadenfreude-pleasure at others' misfortunes-is a multidetermined social emotion
      which involves reward processing, mentalising and perspective-taking abilities.
      Patients with Huntington's disease (HD) exhibit reductions of this experience,
      suggesting a role of striatal degeneration in such impairment. However, no study
      has directly assessed the relationship between regional brain atrophy in HD and
      reduced schadenfreude. Here, we assessed whether grey matter (GM) atrophy in
      patients with HD correlates with ratings of schadenfreude. First, we compared the
      performance of 20 patients with HD and 23 controls on an experimental task
      designed to trigger schadenfreude and envy (another social emotion acting as a
      control condition). Second, we compared GM volume between groups. Third, we
      examined brain regions where atrophy might be associated with specific
      impairments in the patients. While both groups showed similar ratings of envy,
      patients with HD reported lower schadenfreude. The latter pattern was related to
      atrophy in regions of the reward system (ventral striatum) and the mentalising
      network (precuneus and superior parietal lobule). Our results shed light on the
      intertwining of reward and socioemotional processes in schadenfreude, while
      offering novel evidence about their neural correlates.

PMID- 28765321
TI  - Erratum. Weight Loss After Bariatric Surgery Reverses Insulin-Induced Increases
      in Brain Glucose Metabolism of the Morbidly Obese. Diabetes 2013;62:2747-2751.

PMID- 28765322
TI  - Structural Basis and Genotype-Phenotype Correlations of INSR Mutations Causing
      Severe Insulin Resistance.
AB  - The insulin receptor (INSR) gene was analyzed in four patients with severe
      insulin resistance, revealing five novel mutations and a deletion that removed
      exon 2. A patient with Donohue syndrome (DS) had a novel p.V657F mutation in the
      second fibronectin type III domain (FnIII-2), which contains the alpha-beta
      cleavage site and part of the insulin-binding site. The mutant INSR was expressed
      in Chinese hamster ovary cells, revealing that it reduced insulin proreceptor
      processing and impaired activation of downstream signaling cascades. Using online
      databases, we analyzed 82 INSR missense mutations and demonstrated that mutations
      causing DS were more frequently located in the FnIII domains than those causing
      the milder type A insulin resistance (P = 0.016). In silico structural analysis
      revealed that missense mutations predicted to severely impair hydrophobic core
      formation and stability of the FnIII domains all caused DS, whereas those
      predicted to produce localized destabilization and to not affect folding of the
      FnIII domains all caused the less severe Rabson-Mendenhall syndrome. These
      results suggest the importance of the FnIII domains, provide insight into the
      molecular mechanism of severe insulin resistance, will aid early diagnosis, and
      will provide potential novel targets for treating extreme insulin resistance.

PMID- 28765323
TI  - Tumor-Treating Fields: A Fourth Modality in Cancer Treatment.
AB  - Despite major advances in therapy, cancer continues to be a leading cause of
      mortality. In addition, toxicities of traditional therapies pose a significant
      challenge to tolerability and adherence. TTFields, a noninvasive anticancer
      treatment modality, utilizes alternating electric fields at specific frequencies
      and intensities to selectively disrupt mitosis in cancerous cells. TTFields
      target proteins crucial to the cell cycle, leading to mitotic arrest and
      apoptosis. TTFields also facilitate an antitumor immune response. Clinical trials
      of TTFields have proven safe and efficacious in patients with glioblastoma
      multiforme (GBM), and are FDA approved for use in newly diagnosed and recurrent
      GBM. Trials in other localized solid tumors are ongoing. Clin Cancer Res; 24(2);
      266-75. (c)2017 AACR.

PMID- 28765324
TI  - Glesatinib Exhibits Antitumor Activity in Lung Cancer Models and Patients
      Harboring MET Exon 14 Mutations and Overcomes Mutation-mediated Resistance to
      Type I MET Inhibitors in Nonclinical Models.
AB  - Purpose:MET exon 14 deletion (METex14 del) mutations represent a novel class of
      non-small cell lung cancer (NSCLC) driver mutations. We evaluated glesatinib, a
      spectrum-selective MET inhibitor exhibiting a type II binding mode, in METex14
      del-positive nonclinical models and NSCLC patients and assessed its ability to
      overcome resistance to type I MET inhibitors.Experimental Design: As most MET
      inhibitors in clinical development bind the active site with a type I binding
      mode, we investigated mechanisms of acquired resistance to each MET inhibitor
      class utilizing in vitro and in vivo models and in glesatinib clinical
      trials.Results: Glesatinib inhibited MET signaling, demonstrated marked
      regression of METex14 del-driven patient-derived xenografts, and demonstrated a
      durable RECIST partial response in a METex14 del mutation-positive patient
      enrolled on a glesatinib clinical trial. Prolonged treatment of nonclinical
      models with selected MET inhibitors resulted in differences in resistance
      kinetics and mutations within the MET activation loop (i.e., D1228N, Y1230C/H)
      that conferred resistance to type I MET inhibitors, but remained sensitive to
      glesatinib. In vivo models exhibiting METex14 del/A-loop double mutations and
      resistance to type I inhibitors exhibited a marked response to glesatinib.
      Finally, a METex14 del mutation-positive NSCLC patient who responded to
      crizotinib but later relapsed, demonstrated a mixed response to glesatinib
      including reduction in size of a MET Y1230H mutation-positive liver metastasis
      and concurrent loss of detection of this mutation in plasma DNA.Conclusions:
      Together, these data demonstrate that glesatinib exhibits a distinct mechanism of
      target inhibition and can overcome resistance to type I MET inhibitors. Clin
      Cancer Res; 23(21); 6661-72. (c)2017 AACR.

PMID- 28765325
TI  - Diverse BRCA1 and BRCA2 Reversion Mutations in Circulating Cell-Free DNA of
      Therapy-Resistant Breast or Ovarian Cancer.
AB  - Purpose: Resistance to platinum-based chemotherapy or PARP inhibition in germline
      BRCA1 or BRCA2 mutation carriers may occur through somatic reversion mutations or
      intragenic deletions that restore BRCA1 or BRCA2 function. We assessed whether
      BRCA1/2 reversion mutations could be identified in circulating cell-free DNA
      (cfDNA) of patients with ovarian or breast cancer previously treated with
      platinum and/or PARP inhibitors.Experimental Design: cfDNA from 24 prospectively
      accrued patients with germline BRCA1 or BRCA2 mutations, including 19 patients
      with platinum-resistant/refractory ovarian cancer and five patients with platinum
      and/or PARP inhibitor pretreated metastatic breast cancer, was subjected to
      massively parallel sequencing targeting all exons of 141 genes and all exons and
      introns of BRCA1 and BRCA2 Functional studies were performed to assess the impact
      of the putative BRCA1/2 reversion mutations on BRCA1/2 function.Results: Diverse
      and often polyclonal putative BRCA1 or BRCA2 reversion mutations were identified
      in cfDNA from four patients with ovarian cancer (21%) and from two patients with
      breast cancer (40%). BRCA2 reversion mutations were detected in cfDNA prior to
      PARP inhibitor treatment in a patient with breast cancer who did not respond to
      treatment and were enriched in plasma samples after PARP inhibitor therapy. Foci
      formation and immunoprecipitation assays suggest that a subset of the putative
      reversion mutations restored BRCA1/2 function.Conclusions: Putative BRCA1/2
      reversion mutations can be detected by cfDNA sequencing analysis in patients with
      ovarian and breast cancer. Our findings warrant further investigation of cfDNA
      sequencing to identify putative BRCA1/2 reversion mutations and to aid the
      selection of patients for PARP inhibition therapy. Clin Cancer Res; 23(21); 6708
      20. (c)2017 AACR.

PMID- 28765326
TI  - Outcome of Azacitidine Therapy in Acute Myeloid Leukemia Is not Improved by
      Concurrent Vorinostat Therapy but Is Predicted by a Diagnostic Molecular
      Signature.
AB  - Purpose: Azacitidine (AZA) is a novel therapeutic option in older patients with
      acute myeloid leukemia (AML), but its rational utilization is compromised by the
      fact that neither the determinants of clinical response nor its mechanism of
      action are defined. Co-administration of histone deacetylase inhibitors, such as
      vorinostat (VOR), is reported to improve the clinical activity of AZA, but this
      has not been prospectively studied in patients with AML.Experimental Design: We
      compared outcomes in 259 adults with AML (n = 217) and MDS (n = 42) randomized to
      receive either AZA monotherapy (75 mg/m2 * 7 days every 28 days) or AZA combined
      with VOR 300 mg twice a day on days 3 to 9 orally. Next-generation sequencing was
      performed in 250 patients on 41 genes commonly mutated in AML. Serial
      immunophenotyping of progenitor cells was performed in 47 patients.Results: Co
      administration of VOR did not increase the overall response rate (P = 0.84) or
      overall survival (OS; P = 0.32). Specifically, no benefit was identified in
      either de novo or relapsed AML. Mutations in the genes CDKN2A (P = 0.0001), IDH1
      (P = 0.004), and TP53 (P = 0.003) were associated with reduced OS. Lymphoid
      multipotential progenitor populations were greatly expanded at diagnosis and
      although reduced in size in responding patients remained detectable throughout
      treatment.Conclusions: This study demonstrates no benefit of concurrent
      administration of VOR with AZA but identifies a mutational signature predictive
      of outcome after AZA-based therapy. The correlation between heterozygous loss of
      function CDKN2A mutations and decreased OS implicates induction of cell-cycle
      arrest as a mechanism by which AZA exerts its clinical activity. Clin Cancer Res;
      23(21); 6430-40. (c)2017 AACR.

PMID- 28765327
TI  - The KMT1A-GATA3-STAT3 Circuit Is a Novel Self-Renewal Signaling of Human Bladder
      Cancer Stem Cells.
AB  - Purpose: Bladder cancer is one of the most common urinary malignancies worldwide
      characterized by a high rate of recurrence and no targeted therapy method.
      Bladder cancer stem cells (BCSCs) play a crucial role in tumor initiation,
      metastasis, and drug resistance. However, the regulatory signaling and self
      renewal mechanisms of BCSCs remain largely unknown. Here, we identified a novel
      signal, the KMT1A-GATA3-STAT3 circuit, which promoted the self-renewal and
      tumorigenicity of human BCSCs.Experimental Design: In a discovery step, human
      BCSCs and bladder cancer non-stem cells (BCNSCs) isolated from primary bladder
      cancer samples #1 and #2, and the bladder cancer cell line EJ were analyzed by
      transcriptome microarray. In a validation step, 10 paired bladder cancer and
      normal tissues, different tumor cell lines, the public microarray datasets of
      human bladder cancer, and The Cancer Genome Atlas database were applied for the
      verification of gene expression.Results: KMT1A was highly expressed and
      responsible for the increase of tri-methylating lysine 9 of histone H3 (H3K9me3)
      modification in BCSCs compared with either BCNSCs or normal bladder tissue. GATA3
      bound to the -1710~-1530 region of STAT3 promoter and repressed its
      transcription. H3K9me3 modification on the -1351~-1172bp region of the GATA3
      promoter mediated by KMT1A repressed the transcription of GATA3 and upregulated
      the expression of STAT3. In addition, the activated STAT3 triggered self-renewal
      of BCSCs. Furthermore, depletion of KMT1A or STAT3 abrogated the formation of
      BCSC tumorspheres and xenograft tumors.Conclusions: KMT1A positively regulated
      the self-renewal and tumorigenicity of human BCSCs via KMT1A-GATA3-STAT3 circuit,
      in which KMT1A could be a promising target for bladder cancer therapy. Clin
      Cancer Res; 23(21); 6673-85. (c)2017 AACR.

PMID- 28765328
TI  - Phase I Dose-Escalation Study of the Anti-CD70 Antibody ARGX-110 in Advanced
      Malignancies.
AB  - Purpose: The purpose of this study was to evaluate safety, pharmacokinetics,
      pharmacodynamics, and preliminary antitumor efficacy of ARGX-110, a glyco
      engineered monoclonal antibody, targeting CD70, in patients with CD70 expressing
      advanced malignancies.Experimental Design: Dose escalation with a sequential 3+3
      design was performed in five steps at the 0.1, 1, 2, 5, and 10 mg/kg dose levels
      (N = 26). ARGX-110 was administered intravenously every 3 weeks until progression
      or intolerable toxicity. Dose-limiting toxicity was evaluated in the 21 days
      following the first ARGX-110 administration (Cycle 1). Samples for
      pharmacokinetics and pharmacodynamics were collected.Results: Dose-limiting
      toxicity was not observed and the maximum tolerated dose was not reached. ARGX
      110 was generally well tolerated, with no dose-related increase in treatment
      emergent adverse events (TEAE). The most common TEAE were fatigue and drug
      related infusion-related reactions (IRR). Of the 20 SAEs reported, five events,
      all IRRs, were considered related to ARGX-110. ARGX-110 demonstrates dose
      proportionality over the dose range 1 to 10 mg/kg, but not at 0.1 mg/kg and a
      terminal half-life of 10 to 13 days. The best overall response was stable disease
      (14/26) in all 26 evaluable patients with various malignancies and the mean
      duration of treatment was 15 weeks. No dose-response related antitumor activity
      was observed, but biomarker readouts provided signs of biological activity,
      particularly in patients with hematologic malignancies.Conclusions: This dose
      escalation phase I trial provides evidence of good tolerability of ARGX-110,
      pharmacokinetics, and preliminary antitumor activity at all dose levels in
      generally heavily pretreated patients with advanced CD70-positive malignancies.
      Clin Cancer Res; 23(21); 6411-20. (c)2017 AACR.

PMID- 28765330
TI  - Genome Stability by DNA Polymerase beta in Neural Progenitors Contributes to
      Neuronal Differentiation in Cortical Development.
AB  - DNA repair is crucial for genome stability in the developing cortex, as somatic
      de novo mutations cause neurological disorders. However, how DNA repair
      contributes to neuronal development is largely unknown. To address this issue, we
      studied the spatiotemporal roles of DNA polymerase beta (Polbeta), a key enzyme
      in DNA base excision repair pathway, in the developing cortex using distinct
      forebrain-specific conditional knock-out mice, Emx1-Cre/Polbeta fl/fl and Nex
      Cre/Polbeta fl/fl mice. Polbeta expression was absent in both neural progenitors
      and postmitotic neurons in Emx1-Cre/Polbeta fl/fl mice, whereas only postmitotic
      neurons lacked Polbeta expression in Nex-Cre/Polbeta fl/fl mice. We found that
      DNA double-strand breaks (DSBs) were frequently detected during replication in
      cortical progenitors of Emx1-Cre/Polbeta fl/fl mice. Increased DSBs remained in
      postmitotic cells, which resulted in p53-mediated neuronal apoptosis. This
      neuronal apoptosis caused thinning of the cortical plate, although laminar
      structure was normal. In addition, accumulated DSBs also affected growth of
      corticofugal axons but not commissural axons. These phenotypes were not observed
      in Nex-Cre/Polbeta fl/fl mice. Moreover, cultured Polbeta-deficient neural
      progenitors exhibited higher sensitivity to the base-damaging agent
      methylmethanesulfonate, resulting in enhanced DSB formation. Similar damage was
      found by vitamin C treatment, which induces TET1-mediated DNA demethylation via 5
      hydroxymethylcytosine. Together, genome stability mediated by Polbeta-dependent
      base excision repair is crucial for the competence of neural progenitors, thereby
      contributing to neuronal differentiation in cortical development.SIGNIFICANCE
      STATEMENT DNA repair is crucial for development of the nervous system. However,
      how DNA polymerase beta (Polbeta)-dependent DNA base excision repair pathway
      contributes to the process is still unknown. We found that loss of Polbeta in
      cortical progenitors rather than postmitotic neurons led to catastrophic DNA
      double-strand breaks (DSBs) during replication and p53-mediated neuronal
      apoptosis, which resulted in thinning of the cortical plate. The DSBs also
      affected corticofugal axon growth in surviving neurons. Moreover, induction of
      base damage and DNA demethylation intermediates in the genome increased DSBs in
      cultured Polbeta-deficient neural progenitors. Thus, genome stability by Polbeta
      dependent base excision repair in neural progenitors is required for the
      viability and differentiation of daughter neurons in the developing nervous
      system.

PMID- 28765329
TI  - Overcoming Acquired Resistance to AZD9291, A Third-Generation EGFR Inhibitor,
      through Modulation of MEK/ERK-Dependent Bim and Mcl-1 Degradation.
AB  - Purpose: The mechanisms accounting for anticancer activity of AZD9291
      (osimertinib or TAGRISSO), an approved third-generation EGFR inhibitor, in EGFR
      mutant non-small cell lung cancer (NSCLC) cells and particularly for the
      subsequent development of acquired resistance are unclear and thus are the focus
      of this study.Experimental Design: AZD9219-resistant cell lines were established
      by exposing sensitive cell lines to AZD9291. Protein alterations were detected
      with Western blotting. Apoptosis was measured with annexin V/flow cytometry.
      Growth-inhibitory effects of tested drugs were evaluated in vitro with cell
      number estimation and colony formation assay and in vivo with mouse xenograft
      models. Protein degradation was determined by comparing protein half-lives and
      inhibiting proteasome. Gene knockdown were achieved with siRNA or shRNA.Results:
      AZD9291 potently induced apoptosis in EGFR-mutant NSCLC cell lines, in which ERK
      phosphorylation was suppressed accompanied with Bim elevation and Mcl-1 reduction
      likely due to enhanced Mcl-1 degradation and increased Bim stability. Blocking
      Bim elevation by gene knockdown or enforcing Mcl-1 expression attenuated or
      abolished AZD9291-induced apoptosis. Moreover, AZD9291 lost its ability to
      modulate Bim and Mcl-1 levels in AZD9291-resistant cell lines. The combination of
      a MEK inhibitor with AZD9291 restores the sensitivity of AZD9291-resistant cells
      including those with C797S mutation to undergo apoptosis and growth regression in
      vitro and in vivoConclusions: Modulation of MEK/ERK-dependent Bim and Mcl-1
      degradation critically mediates sensitivity and resistance of EGFR-mutant NSCLC
      cells to AZD9291 and hence is an effective strategy to overcome acquired
      resistance to AZD9291. Clin Cancer Res; 23(21); 6567-79. (c)2017 AACR.

PMID- 28765331
TI  - Visual Perceptual Echo Reflects Learning of Regularities in Rapid Luminance
      Sequences.
AB  - A novel neural signature of active visual processing has recently been described
      in the form of the "perceptual echo", in which the cross-correlation between a
      sequence of randomly fluctuating luminance values and occipital
      electrophysiological signals exhibits a long-lasting periodic (~100 ms cycle)
      reverberation of the input stimulus (VanRullen and Macdonald, 2012). As yet,
      however, the mechanisms underlying the perceptual echo and its function remain
      unknown. Reasoning that natural visual signals often contain temporally
      predictable, though nonperiodic features, we hypothesized that the perceptual
      echo may reflect a periodic process associated with regularity learning. To test
      this hypothesis, we presented subjects with successive repetitions of a rapid
      nonperiodic luminance sequence, and examined the effects on the perceptual echo,
      finding that echo amplitude linearly increased with the number of presentations
      of a given luminance sequence. These data suggest that the perceptual echo
      reflects a neural signature of regularity learning.Furthermore, when a set of
      repeated sequences was followed by a sequence with inverted luminance polarities,
      the echo amplitude decreased to the same level evoked by a novel stimulus
      sequence. Crucially, when the original stimulus sequence was re-presented, the
      echo amplitude returned to a level consistent with the number of presentations of
      this sequence, indicating that the visual system retained sequence-specific
      information, for many seconds, even in the presence of intervening visual input.
      Altogether, our results reveal a previously undiscovered regularity learning
      mechanism within the human visual system, reflected by the perceptual
      echo.SIGNIFICANCE STATEMENT How the brain encodes and learns fast-changing but
      nonperiodic visual input remains unknown, even though such visual input
      characterizes natural scenes. We investigated whether the phenomenon of
      "perceptual echo" might index such learning. The perceptual echo is a long
      lasting reverberation between a rapidly changing visual input and evoked neural
      activity, apparent in cross-correlations between occipital EEG and stimulus
      sequences, peaking in the alpha (~10 Hz) range. We indeed found that perceptual
      echo is enhanced by repeatedly presenting the same visual sequence, indicating
      that the human visual system can rapidly and automatically learn regularities
      embedded within fast-changing dynamic sequences. These results point to a
      previously undiscovered regularity learning mechanism, operating at a rate
      defined by the alpha frequency.

PMID- 28765333
TI  - Selective Phosphorylation of AMPA Receptor Contributes to the Network of Long
      Term Potentiation in the Anterior Cingulate Cortex.
AB  - Phosphorylation of AMPA receptor GluA1 plays important roles in synaptic
      potentiation. Most previous studies have been performed in the hippocampus, while
      the roles of GluA1 phosphorylation in the cortex remain unknown. Here we
      investigated the involvement of the phosphorylation of GluA1 in the LTP in the
      anterior cingulate cortex (ACC) using mice with a GluA1 knock-in mutation at the
      PKA phosphorylation site serine 845 (s845A) or CaMKII/PKC phosphorylation site
      serine 831 (s831A). The network LTP, which is constructed by multiple recordings
      of LTP at different locations within the ACC, was also investigated. We found
      that the expression of LTP and network LTP was significantly impaired in the
      s845A mice, but not in the s831A mice. By contrast, basal synaptic transmission
      and NMDA receptor-mediated responses were not affected. Furthermore, to uncover
      potential information under the current acquired data, a new method for
      reconstruction and better visualization of the signals was developed to observe
      the spatial localizations and dynamic temporal changes of fEPSP signals and
      multiple LTP responses within the ACC circuit. Our results provide strong
      evidence that PKA phosphorylation of the GluA1 is important for the network LTP
      expression in the ACC.SIGNIFICANCE STATEMENT Previous studies have shown that PKA
      and PKC phosphorylation of AMPA receptor GluA1 plays critical roles in LTP in the
      hippocampus, while the roles of GluA1 phosphorylation in the cortex remain
      unknown. In the present study, by combining a 64-channel multielectrode system
      and a novel analysis and visualization method, we observed the accurate spatial
      localization and dynamic temporal changes of network fEPSP signals and LTP
      responses within the ACC circuit and found that PKA phosphorylation, but not PKC
      phosphorylation, of the GluA1 is required for LTP in the ACC.

PMID- 28765335
TI  - New Evidence on the Association between Prediagnostic Thyroid-Stimulating Hormone
      Levels and Thyroid Cancer Risk.

PMID- 28765332
TI  - N1-Src Kinase Is Required for Primary Neurogenesis in Xenopus tropicalis.
AB  - The presence of the neuronal-specific N1-Src splice variant of the C-Src tyrosine
      kinase is conserved through vertebrate evolution, suggesting an important role in
      complex nervous systems. Alternative splicing involving an N1-Src-specific
      microexon leads to a 5 or 6 aa insertion into the SH3 domain of Src. A prevailing
      model suggests that N1-Src regulates neuronal differentiation via cytoskeletal
      dynamics in the growth cone. Here we investigated the role of n1-src in the early
      development of the amphibian Xenopus tropicalis, and found that n1-src expression
      is regulated in embryogenesis, with highest levels detected during the phases of
      primary and secondary neurogenesis. In situ hybridization analysis, using locked
      nucleic acid oligo probes complementary to the n1-src microexon, indicates that
      n1-src expression is highly enriched in the open neural plate during neurula
      stages and in the neural tissue of adult frogs. Given the n1-src expression
      pattern, we investigated a possible role for n1-src in neurogenesis. Using splice
      site-specific antisense morpholino oligos, we inhibited n1-src splicing, while
      preserving c-src expression. Differentiation of neurons in the primary nervous
      system is reduced in n1-src-knockdown embryos, accompanied by a severely impaired
      touch response in later development. These data reveal an essential role for n1
      src in amphibian neural development and suggest that alternative splicing of C
      Src in the developing vertebrate nervous system evolved to regulate
      neurogenesis.SIGNIFICANCE STATEMENT The Src family of nonreceptor tyrosine
      kinases acts in signaling pathways that regulate cell migration, cell adhesion,
      and proliferation. Srcs are also enriched in the brain, where they play key roles
      in neuronal development and neurotransmission. Vertebrates have evolved a neuron
      specific splice variant of C-Src, N1-Src, which differs from C-Src by just 5 or 6
      aa. N1-Src is poorly understood and its high similarity to C-Src has made it
      difficult to delineate its function. Using antisense knockdown of the n1-src
      microexon, we have studied neuronal development in the Xenopus embryo in the
      absence of n1-src, while preserving c-src Loss of n1-src causes a striking
      absence of primary neurogenesis, implicating n1-src in the specification of
      neurons early in neural development.

PMID- 28765336
TI  - New Directions in Cancer Control and Population Sciences.
AB  - Cancer control science has been evolving since it first became a focus for cancer
      research and program activities a century ago. The evolution of the field has
      responded to historical megatrends along the way that keep it relevant to the
      cancer-related needs of society. This commentary describes some of the key trends
      and developments now influencing cancer control and population sciences that
      reflect societal change and new tools and concepts in modern biomedical science.
      New directions include the impact of climate change, health care delivery
      research, the growth of population health science, data science, precision
      medicine, data sharing, implementation science, and new technologies, including
      social media and new geospatial methodologies. Cancer Epidemiol Biomarkers Prev;
      26(8); 1165-9. (c)2017 AACR.

PMID- 28765337
TI  - Tanning and Teens: Is Indoor Exposure the Tip of the Iceberg?
AB  - Because of recent state regulations and the reduced availability of free-standing
      tanning salons, indoor tanning (IT) prevalence is beginning to decline. This may
      lead to unintended consequences, such as increases in outdoor intentional
      tanning. We advance a series of research directions to track and intervene to
      address all forms of intentional tanning. First, we advocate for enforcement of
      IT regulation and encourage collection of data on tanning salon compliance and
      alternative IT strategies. Second, we suggest questions about outdoor and IT
      should be included in national surveys. Third, we need to understand the
      potentially complex patterns of indoor and outdoor tanning that may exist among
      those who tan. Fourth, research examining changing motivations for intentional
      tanning is needed. Finally, IT intervention studies should include outdoor
      tanning as an outcome to examine the effect of interventions on these related
      risk behaviors. These advances will ensure the development of novel interventions
      to address intentional tanning through multiple routes, and to avoid any
      unintended negative consequence of IT regulation. The promising downward
      direction of IT use in the United States should now lead the public health field
      to sharpen its focus on outdoor tanning. Cancer Epidemiol Biomarkers Prev; 26(8);
      1170-4. (c)2017 AACR.

PMID- 28765338
TI  - Periodontal Disease and Incident Cancer Risk among Postmenopausal Women: Results
      from the Women's Health Initiative Observational Cohort.
AB  - Background: Periodontal pathogens have been isolated from precancerous and
      cancerous lesions and also shown to promote a procarcinogenic microenvironment.
      Few studies have examined periodontal disease as a risk factor for total cancer,
      and none have focused on older women. We examined whether periodontal disease is
      associated with incident cancer among postmenopausal women in the Women's Health
      Initiative Observational Study.Methods: Our prospective cohort study comprised
      65,869 women, ages 54 to 86 years. Periodontal disease information was obtained
      via self-report questionnaires administered between 1999 and 2003, whereas
      ascertainment of cancer outcomes occurred through September 2013, with a maximum
      follow-up period of 15 years. Physician-adjudicated incident total cancers were
      the main outcomes and site-specific cancers were secondary outcomes. HRs and 95%
      confidence intervals (CI) were calculated using Cox proportional hazards
      regression. All analyses were conducted two-sided.Results: During a mean follow
      up of 8.32 years, 7,149 cancers were identified. Periodontal disease history was
      associated with increased total cancer risk (multivariable-adjusted HR, 1.14; 95%
      CI, 1.08-1.20); findings were similar in analyses limited to 34,097 never-smokers
      (HR, 1.12; 95% CI, 1.04-1.22). Associations were observed for breast (HR, 1.13;
      95% CI, 1.03-1.23), lung (HR, 1.31; 95% CI, 1.14-1.51), esophagus (HR, 3.28; 95%
      CI, 1.64-6.53), gallbladder (HR, 1.73; 95% CI, 1.01-2.95), and melanoma skin (HR,
      1.23; 95% CI, 1.02-1.48) cancers. Stomach cancer was borderline (HR, 1.58; 95%
      CI, 0.94-2.67).Conclusions: Periodontal disease increases risk of total cancer
      among older women, irrespective of smoking, and certain anatomic sites appear to
      be vulnerable. Impact: Our findings support the need for further understanding of
      the effect of periodontal disease on cancer outcomes. Cancer Epidemiol Biomarkers
      Prev; 26(8); 1255-65. (c)2017 AACR.

PMID- 28765339
TI  - Use of Calcium Channel Blockers and Breast Cancer Risk in the Women's Health
      Initiative.
AB  - Background: Use of calcium channel blockers (CCBs) has been associated with
      increased risk of breast cancer in some, but not all, studies. Differences in
      reported associations from prior studies may be due, in part, to inadequate
      control of confounding factors.Methods: Participants were 28,561 postmenopausal
      women from the Women's Health Initiative who reported use of either CCBs or other
      antihypertensive medications (AHMs) at baseline; 1,402 incident breast cancer
      cases were diagnosed during 12 years of follow-up. Adjusted Cox regression models
      were used to estimate HRs and 95% confidence intervals (CI) for the associations
      between CCB use relative to other AHM use and breast cancer risk.Results: Use of
      CCBs was not associated with breast cancer risk (HR, 1.06; 95% CI, 0.94-1.20)
      relative to use of other AHMs. Associations approximated the null value when CCBs
      were considered by duration of use, length of action, or drug class.Conclusions:
      We provide additional evidence that CCBs do not influence breast cancer risk in
      postmenopausal women.Impact: The results from this study, which includes strong
      control for potential confounding factors, cast doubt on increases in risk with
      CCBs. Cancer Epidemiol Biomarkers Prev; 26(8); 1345-8. (c)2017 AACR.

PMID- 28765340
TI  - Lack of Association for Reported Endocrine Pancreatic Cancer Risk Loci in the
      PANDoRA Consortium.
AB  - Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms for which
      very little is known about either environmental or genetic risk factors. Only a
      handful of association studies have been performed so far, suggesting a small
      number of risk loci.Methods: To replicate the best findings, we have selected 16
      SNPs suggested in previous studies to be relevant in PNET etiogenesis. We
      genotyped the selected SNPs (rs16944, rs1052536, rs1059293, rs1136410, rs1143634,
      rs2069762, rs2236302, rs2387632, rs3212961, rs3734299, rs3803258, rs4962081,
      rs7234941, rs7243091, rs12957119, and rs1800629) in 344 PNET sporadic cases and
      2,721 controls in the context of the PANcreatic Disease ReseArch (PANDoRA)
      consortium.Results: After correction for multiple testing, we did not observe any
      statistically significant association between the SNPs and PNET risk. We also
      used three online bioinformatic tools (HaploReg, RegulomeDB, and GTEx) to predict
      a possible functional role of the SNPs, but we did not observe any clear
      indication.Conclusions: None of the selected SNPs were convincingly associated
      with PNET risk in the PANDoRA consortium.Impact: We can exclude a major role of
      the selected polymorphisms in PNET etiology, and this highlights the need for
      replication of epidemiologic findings in independent populations, especially in
      rare diseases such as PNETs. Cancer Epidemiol Biomarkers Prev; 26(8); 1349-51.
      (c)2017 AACR.

PMID- 28765342
TI  - Exercise as Medicine for Children with Arthritis.

PMID- 28765343
TI  - Risk of Thrombosis in Sjogren Syndrome: The Open Question of Endothelial Function
      Immune-mediated Dysregulation.

PMID- 28765341
TI  - Coffee and Green Tea Consumption and Subsequent Risk of Malignant Lymphoma and
      Multiple Myeloma in Japan: The Japan Public Health Center-based Prospective
      Study.
AB  - Background: The aim of this study was to investigate the association of coffee
      and green tea consumption and the risk of malignant lymphoma and multiple myeloma
      in a large-scale population-based cohort study in Japan.Methods: In this
      analysis, a total of 95,807 Japanese subjects (45,937 men and 49,870 women; ages
      40-69 years at baseline) of the Japan Public Health Center-based Prospective
      Study who completed a questionnaire about their coffee and green tea consumption
      were followed up until December 31, 2012, for an average of 18 years. HRs and 95%
      confidence intervals were estimated using a Cox regression model adjusted for
      potential confounders as a measure of association between the risk of malignant
      lymphoma and multiple myeloma associated with coffee and green tea consumption at
      baseline.Results: During the follow-up period, a total of 411 malignant lymphoma
      cases and 138 multiple myeloma cases were identified. Overall, our findings
      showed no significant association between coffee or green tea consumption and the
      risk of malignant lymphoma or multiple myeloma for both sexes.Conclusions: In
      this study, we observed no significant association between coffee or green tea
      consumption and the risk of malignant lymphoma or multiple myeloma.Impact: Our
      results do not support an association between coffee or green tea consumption and
      the risk of malignant lymphoma or multiple myeloma. Cancer Epidemiol Biomarkers
      Prev; 26(8); 1352-6. (c)2017 AACR.

PMID- 28765344
TI  - The Accuracy of Self-report in Rheumatic Diseases.

PMID- 28765345
TI  - Lumbar Spine Chondrocalcinosis.

PMID- 28765346
TI  - Pitfalls of PACNS: A Rare Case of Central Nervous System Vasculitis Associated
      with Toxoplasmosis.

PMID- 28765347
TI  - Maintenance of Low Disease Activity following Tumor Necrosis Factor Inhibitor
      Dose Tapering in Ankylosing Spondylitis.

PMID- 28765348
TI  - Adherence to Ophthalmologic Monitoring for Antimalarial Toxicity in a Lupus
      Cohort.

PMID- 28765350
TI  - Writing for Publication 101: Why the Abstract Is So Important.

PMID- 28765351
TI  - Place Atrium to Water Seal (PAWS): Assessing Wall Suction Versus No Suction for
      Chest Tubes After Open Heart Surgery.
AB  - BACKGROUND: Traditionally chest tubes are set to -20 cm H2O wall suctioning until
      removal to facilitate drainage of blood, fluid, and air from the pleural or
      mediastinal space in patients after open heart surgery. However, no clear
      evidence supports using wall suction in these patients. Some studies in patients
      after pulmonary surgery indicate that using chest tubes with a water seal is
      safer, because this practice decreases duration of chest tube placement and
      eliminates air leaks. OBJECTIVE: To show that changing chest tubes to a water
      seal after 12 hours of wall suction (intervention) is a safe alternative to using
      chest tubes with wall suction until removal of the tubes (usual care) in patients
      after open heart surgery. METHODS: A before-and-after quality improvement design
      was used to evaluate the differences between the 2 chest tube management
      approaches in chest tube complications, output, and duration of placement.
      RESULTS: A total of 48 patients received the intervention; 52 received usual
      care. The 2 groups (intervention vs usual care) did not differ significantly in
      complications (0 vs 2 events; P = .23), chest tube output (H1 = 0.001, P = .97),
      or duration of placement (median, 47 hours for both groups). CONCLUSION: Changing
      chest tubes from wall suction to water seal after 12 hours of wall suction is a
      safe alternative to using wall suctioning until removal of the tubes.

PMID- 28765352
TI  - Identification and Prevention of Secondary Heart Failure: A Case Study.
AB  - Heart failure, a complex clinical syndrome affecting millions of Americans, is
      associated with high morbidity and mortality and a significant financial burden
      on the health care system. Recent health care reform efforts have focused on
      reducing 30-day heart failure hospital readmissions, increasing the cost
      effectiveness of care provided to heart failure patients, and improving health
      outcomes for these patients. This case report describes an acutely ill patient
      with multiple comorbidities who was not initially admitted for heart failure but
      who developed acute decompensated heart failure during his hospital stay. The
      purpose of this in-depth analysis is to discuss the role of bedside nurses and
      advanced practice nurses in managing heart failure, describe the challenges of
      identifying secondary heart failure in patients with complex conditions, and
      suggest methods of improving health-related outcomes to prevent hospital
      readmissions.

PMID- 28765353
TI  - Hemostatic Management of Trauma-Induced Coagulopathy.
AB  - Trauma-induced coagulopathy is a primary factor in many trauma-related
      fatalities. Management hinges upon rapid diagnosis of coagulation abnormalities
      and immediate administration of appropriate hemostatic agents. Use of
      crystalloids and packed red blood cells has traditionally been the core of trauma
      resuscitation, but current massive transfusion protocols include combination
      therapy with fresh frozen plasma and predefined ratios of platelets to packed red
      blood cells, limiting crystalloid administration. Hemostatic agents such as
      tranexamic acid, prothrombin complex concentrate, fibrinogen concentrate, and, in
      cases of refractory bleeding, recombinant activated factor VIIa may also be
      warranted. Goal-directed resuscitation using viscoelastic tools allows specific
      component-centered therapy based on individual clotting abnormalities that may
      limit blood product use and thromboembolic risks and may lead to reduced
      mortality. Because of the complex management of patients with trauma-induced
      coagulopathy, critical care nurses must be familiar with the pathophysiology,
      acute diagnostics, and pharmacotherapeutic options used to treat these patients.

PMID- 28765354
TI  - Levamisole-Adulterated Cocaine Leading to Fatal Vasculitis: A Case Report.
AB  - Cocaine is often "cut" with various additives to increase the profitability of
      the drug. One of the most common additives on today's market is levamisole, an
      anthelmintic medication used to destroy and expel parasitic worms in animals. The
      use of levamisole-contaminated cocaine can result in agranulocytosis and
      vasculitis (inflammation and constriction of small blood vessels). The resulting
      clotting and decrease in peripheral blood flow lead to cutaneous lesions,
      particularly on the ears, face, hands, and feet, and in severe cases can cause
      generalized tissue necrosis throughout the entire body. Treatment is generally
      supportive, and symptoms typically abate with complete cessation of cocaine use.
      However, symptoms may recur with subsequent cocaine use and, as this case
      illustrates, severe neutropenia and extensive vasculitis may lead to overwhelming
      sepsis and death.

PMID- 28765355
TI  - Oxygen Requirements for Acutely and Critically Ill Patients.
AB  - Oxygen administration is often assumed to be required for all patients who are
      acutely or critically ill. However, in many situations, this assumption is not
      based on evidence. Injured body tissues and cells throughout the body respond
      both beneficially and adversely to delivery of supplemental oxygen. Available
      evidence indicates that oxygen administration is not warranted for patients who
      are not hypoxemic, and hyperoxia may contribute to increased tissue damage and
      mortality. Nurses must be aware of implications related to oxygen administration
      for all types of acutely and critically ill patients. These implications include
      having knowledge of oxygenation processes and pathophysiology; assessing global,
      tissue, and organ oxygenation status; avoiding either hypoxia or hyperoxia; and
      creating partnerships with respiratory therapists. Nurses can contribute to
      patients' oxygen status well-being by being proficient in determining each
      patient's specific oxygen needs and appropriate oxygen administration.

PMID- 28765356
TI  - Courageous or Compliant?

PMID- 28765357
TI  - Volume-Based Feeding in Enteral Nutrition: What About Diabetes?

PMID- 28765358
TI  - Protocol-Directed Sedation Versus Non-Protocol-Directed Sedation to Reduce the
      Duration of Mechanical Ventilation in Intensive Care Patients.

PMID- 28765359
TI  - Beacon Award for Excellence: The Impact of Recognition on the Nursing Practice
      Environment.

PMID- 28765360
TI  - Family Visitation in the Adult Intensive Care Unit.

PMID- 28765361
TI  - Predicting the Risk for Hospital-Acquired Pressure Ulcers in Critical Care
      Patients.
AB  - BACKGROUND: Assessments of risk for pressure ulcers in critical care patients may
      not include important predictors. OBJECTIVE: To construct risk-prediction models
      of hospital-acquired pressure ulcers in intensive care patients and compare the
      models' predictive validities with validity of the Braden Scale. METHODS: Data
      were collected retrospectively on patients admitted to intensive care from
      October 2011 through October 2013. Logistic regression and decision trees were
      used to construct the risk-prediction models. Predictive validity was measured by
      using sensitivity, specificity, positive and negative predictive values, and area
      under the curve. RESULTS: With logistic regression analysis, 6 factors were
      significant independent predictors. With the decision tree, 4 types of high-risk
      populations were identified. Predictive validity of Braden Scale scores was lower
      than the validities of the logistic regression and the decision tree models.
      CONCLUSION: Risk for hospital-acquired pressure ulcers is overpredicted with the
      Braden Scale, with low specificity and low positive predictive value.

PMID- 28765362
TI  - Driving Organizational Change From the Bedside: The AACN Clinical Scene
      Investigator Academy.
AB  - BACKGROUND: Staff nurses are pivotal in leading change related to quality
      improvement efforts, although many lack skills to steer change from the bedside.
      The American Association of Critical-Care Nurses (AACN) staff nurse leadership
      program, Clinical Scene Investigator (CSI) Academy, teaches and empowers staff
      nurses in leadership skills and change concepts to translate evidence into
      practice affecting patient outcomes. OBJECTIVES: To describe the curriculum of
      the AACN CSI Academy that provides staff nurses with the leadership skills
      required to create unit-based change projects that positively impact
      patient/family outcomes. METHODS: The curriculum of the Academy included
      leadership topics, communication, change concepts, quality improvement methods,
      project management, and data management and analysis. Each team of participants
      collected project data to show improvements in patient care. The program
      evaluation used many data sources to assess the program effectiveness, relating
      to the professional growth of the participant nurses. The participants assessed
      project patient outcomes, sustainability, and spread. RESULTS: The first cohort
      of CSI participants included 164 direct care nurses from 42 hospitals in 6
      cities. They rated the Academy highly in the program evaluation, and they
      reported that the Academy contributed to their professional development. The
      individual hospital quality improvement projects resulted in positive patient and
      estimated fiscal outcomes that were generally sustained 1 year after the program.
      CONCLUSION: With the skills, tools, and support obtained from participation in
      the CSI Academy, staff nurses can make substantial contributions to their
      organizations in clinical and possibly fiscal outcomes.

PMID- 28765363
TI  - Buckle up: Membrane tension drives lamellipodial network compression and adhesion
      deposition.
AB  - Whether to spread on a surface or to crawl, cells must apply traction forces to
      the underlying substrate via adhesion complexes. In this issue, Pontes et al.
      (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201611117) shed new light on how
      the interplay among membrane tension, the lamellipodial actin network, and
      adhesions coordinate the dynamics of spreading fibroblasts.

PMID- 28765364
TI  - FiloQuant reveals increased filopodia density during breast cancer progression.
AB  - Defective filopodia formation is linked to pathologies such as cancer, wherein
      actively protruding filopodia, at the invasive front, accompany cancer cell
      dissemination. Despite wide biological significance, delineating filopodia
      function in complex systems remains challenging and is particularly hindered by
      lack of compatible methods to quantify filopodia properties. Here, we present
      FiloQuant, a freely available ImageJ plugin, to detect filopodia-like protrusions
      in both fixed- and live-cell microscopy data. We demonstrate that FiloQuant can
      extract quantifiable information, including protrusion dynamics, density, and
      length, from multiple cell types and in a range of microenvironments. In cellular
      models of breast ductal carcinoma in situ, we reveal a link between filopodia
      formation at the cell-matrix interface, in collectively invading cells and 3D
      tumor spheroids, and the in vitro invasive capacity of the carcinoma. Finally,
      using intravital microscopy, we observe that tumor spheroids display filopodia in
      vivo, supporting a potential role for these protrusions during tumorigenesis.

PMID- 28765365
TI  - Cytochrome c peroxidase facilitates the beneficial use of H2O2 in prokaryotes.

PMID- 28765366
TI  - Mercury, volcanism, and mass extinctions.

PMID- 28765367
TI  - Polycomb-mediated chromatin loops revealed by a subkilobase-resolution chromatin
      interaction map.
AB  - The locations of chromatin loops in Drosophila were determined by Hi-C (chemical
      cross-linking, restriction digestion, ligation, and high-throughput DNA
      sequencing). Whereas most loop boundaries or "anchors" are associated with CTCF
      protein in mammals, loop anchors in Drosophila were found most often in
      association with the polycomb group (PcG) protein Polycomb (Pc), a subunit of
      polycomb repressive complex 1 (PRC1). Loops were frequently located within
      domains of PcG-repressed chromatin. Promoters located at PRC1 loop anchors
      regulate some of the most important developmental genes and are less likely to be
      expressed than those not at PRC1 loop anchors. Although DNA looping has most
      commonly been associated with enhancer-promoter communication, our results
      indicate that loops are also associated with gene repression.

PMID- 28765369
TI  - Role of clusterin in the brain vascular clearance of amyloid-beta.

PMID- 28765368
TI  - IL-4-secreting eosinophils promote endometrial stromal cell proliferation and
      prevent Chlamydia-induced upper genital tract damage.
AB  - Genital Chlamydia trachomatis infections in women typically are asymptomatic and
      do not cause permanent upper genital tract (UGT) damage. Consistent with this
      presentation, type 2 innate and TH2 adaptive immune responses associated with
      dampened inflammation and tissue repair are elicited in the UGT of Chlamydia
      infected women. Primary C. trachomatis infection of mice also causes no genital
      pathology, but unlike women, does not generate Chlamydia-specific TH2 immunity.
      Herein, we explored the significance of type 2 innate immunity for restricting
      UGT tissue damage in Chlamydia-infected mice, and in initial studies
      intravaginally infected wild-type, IL-10-/-, IL-4-/-, and IL-4Ralpha-/- mice with
      low-dose C. trachomatis inoculums. Whereas Chlamydia was comparably cleared in
      all groups, IL-4-/- and IL-4Ralpha-/- mice displayed endometrial damage not seen
      in wild-type or IL-10-/- mice. Congruent with the aberrant tissue repair in mice
      with deficient IL-4 signaling, we found that IL-4Ralpha and STAT6 signaling
      mediated IL-4-induced endometrial stromal cell (ESC) proliferation ex vivo, and
      that genital administration of an IL-4-expressing adenoviral vector greatly
      increased in vivo ESC proliferation. Studies with IL-4-IRES-eGFP (4get) reporter
      mice showed eosinophils were the main IL-4-producing endometrial leukocyte
      (constitutively and during Chlamydia infection), whereas studies with eosinophil
      deficient mice identified this innate immune cell as essential for endometrial
      repair during Chlamydia infection. Together, our studies reveal IL-4-producing
      eosinophils stimulate ESC proliferation and prevent Chlamydia-induced endometrial
      damage. Based on these results, it seems possible that the robust type 2 immunity
      elicited by Chlamydia infection of human genital tissue may analogously promote
      repair processes that reduce phenotypic disease expression.

PMID- 28765370
TI  - Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and N-cadherin
      balance in mural cell-endothelial cell-regulated barrier function.
AB  - The integrity of the endothelial barrier between circulating blood and tissue is
      important for blood vessel function and, ultimately, for organ homeostasis. Here,
      we developed a vessel-on-a-chip with perfused endothelialized channels lined with
      human bone marrow stromal cells, which adopt a mural cell-like phenotype that
      recapitulates barrier function of the vasculature. In this model, barrier
      function is compromised upon exposure to inflammatory factors such as LPS,
      thrombin, and TNFalpha, as has been observed in vivo. Interestingly, we observed
      a rapid physical withdrawal of mural cells from the endothelium that was
      accompanied by an inhibition of endogenous Rac1 activity and increase in RhoA
      activity in the mural cells themselves upon inflammation. Using a system to
      chemically induce activity in exogenously expressed Rac1 or RhoA within minutes
      of stimulation, we demonstrated RhoA activation induced loss of mural cell
      coverage on the endothelium and reduced endothelial barrier function, and this
      effect was abrogated when Rac1 was simultaneously activated. We further showed
      that N-cadherin expression in mural cells plays a key role in barrier function,
      as CRISPR-mediated knockout of N-cadherin in the mural cells led to loss of
      barrier function, and overexpression of N-cadherin in CHO cells promoted barrier
      function. In summary, this bicellular model demonstrates the continuous and rapid
      modulation of adhesive interactions between endothelial and mural cells and its
      impact on vascular barrier function and highlights an in vitro platform to study
      the biology of perivascular-endothelial interactions.

PMID- 28765371
TI  - Zika plasma viral dynamics in nonhuman primates provides insights into early
      infection and antiviral strategies.
AB  - The recent outbreak of Zika virus (ZIKV) has been associated with fetal
      abnormalities and neurological complications, prompting global concern. Here we
      present a mathematical analysis of the within-host dynamics of plasma ZIKV burden
      in a nonhuman primate model, allowing for characterization of the growth and
      clearance of ZIKV within individual macaques. We estimate that the eclipse phase
      for ZIKV, the time between cell infection and viral production, is most likely
      short (~4 h), the median within-host basic reproductive number R0 is 10.7, the
      rate of viral production is rapid (>25,000 virions d-1), and the lifetime of an
      infected cell while producing virus is ~5 h. We also estimate that the minimum
      number of virions produced by an infected cell over its lifetime is ~5,500. We
      assess the potential effect of an antiviral treatment that blocks viral
      replication, showing that the median time to undetectable plasma viral load (VL)
      can be reduced from ~5 d to ~3 d with a drug concentration ~15 times the drug's
      EC50 when treatment is given prophylactically starting at the time of infection.
      In the case of favipiravir, a polymerase inhibitor with activity against ZIKV, we
      predict a dose of 150 mg/kg given twice a day initiated at the time of infection
      can reduce the peak median VL by ~3 logs and shorten the time to undetectable
      median VL by ~2 d, whereas treatment given 2 d postinfection is mostly
      ineffective in accelerating plasma VL loss in macaques.

PMID- 28765372
TI  - Microfluidic perfusion shows intersarcomere dynamics within single skeletal
      muscle myofibrils.
AB  - The sarcomere is the smallest functional unit of myofibrils in striated muscles.
      Sarcomeres are connected in series through a network of elastic and structural
      proteins. During myofibril activation, sarcomeres develop forces that are
      regulated through complex dynamics among their structures. The mechanisms that
      regulate intersarcomere dynamics are unclear, which limits our understanding of
      fundamental muscle features. Such dynamics are associated with the loss in forces
      caused by mechanical instability encountered in muscle diseases and
      cardiomyopathy and may underlie potential target treatments for such conditions.
      In this study, we developed a microfluidic perfusion system to control one
      sarcomere within a myofibril, while measuring the individual behavior of all
      sarcomeres. We found that the force from one sarcomere leads to adjustments of
      adjacent sarcomeres in a mechanism that is dependent on the sarcomere length and
      the myofibril stiffness. We concluded that the cooperative work of the
      contractile and the elastic elements within a myofibril rules the intersarcomere
      dynamics, with important consequences for muscle contraction.

PMID- 28765373
TI  - Localized stress fluctuations drive shear thickening in dense suspensions.
AB  - Dense particulate suspensions exhibit a dramatic increase in average viscosity
      above a critical, material-dependent shear stress. This thickening changes from
      continuous to discontinuous as the concentration is increased. Using direct
      measurements of spatially resolved surface stresses in the continuous thickening
      regime, we report the existence of clearly defined dynamic localized regions of
      substantially increased stress that appear intermittently at stresses above the
      critical stress. With increasing applied stress, these regions occupy an
      increasing fraction of the system, and the increase accounts quantitatively for
      the observed shear thickening. The regions represent high-viscosity fluid phases,
      with a size determined by the distance between the shearing surfaces and a
      viscosity that is nearly independent of shear rate but that increases rapidly
      with concentration. Thus, we find that continuous shear thickening arises from
      increasingly frequent localized discontinuous transitions between distinct fluid
      phases with widely differing viscosities.

PMID- 28765374
TI  - Toward broadband mechanical spectroscopy.
AB  - Diverse material classes exhibit qualitatively similar behavior when made viscous
      upon cooling toward the glass transition, suggesting a common theoretical basis.
      We used seven different measurement methods to determine the mechanical
      relaxation kinetics of a prototype molecular glass former over a temporal range
      of 13 decades and over a temperature range spanning liquid to glassy states. The
      data conform to time-temperature superposition for the main (alpha) process and
      to a scaling relation of schematic mode-coupling theory. The broadband mechanical
      measurements demonstrated have fundamental and practical applications in polymer
      science, geophysics, multifunctional materials, and other areas.

PMID- 28765375
TI  - Evidence for frequency-dependent cortical plasticity in the human brain.
AB  - Frequency-dependent plasticity (FDP) describes adaptation at the synapse in
      response to stimulation at different frequencies. Its consequence on the
      structure and function of cortical networks is unknown. We tested whether
      cortical "resonance," favorable stimulation frequencies at which the sensory
      cortices respond maximally, influenced the impact of FDP on perception,
      functional topography, and connectivity of the primary somatosensory cortex using
      psychophysics and functional imaging (fMRI). We costimulated two digits on the
      hand synchronously at, above, or below the resonance frequency of the
      somatosensory cortex, and tested subjects' accuracy and speed on tactile
      localization before and after costimulation. More errors and slower response
      times followed costimulation at above- or below-resonance, respectively. Response
      times were faster after at-resonance costimulation. In the fMRI, the cortical
      representations of the two digits costimulated above-resonance shifted closer,
      potentially accounting for the poorer performance. Costimulation at-resonance did
      not shift the digit regions, but increased the functional coupling between them,
      potentially accounting for the improved response time. To relate these results to
      synaptic plasticity, we simulated a network of oscillators incorporating Hebbian
      learning. Two neighboring patches embedded in a cortical sheet, mimicking the two
      digit regions, were costimulated at different frequencies. Network activation
      outside the stimulated patches was greatest at above-resonance frequencies,
      reproducing the spread of digit representations seen with fMRI. Connection
      strengths within the patches increased following at-resonance costimulation,
      reproducing the increased fMRI connectivity. We show that FDP extends to the
      cortical level and is influenced by cortical resonance.

PMID- 28765376
TI  - Reply to Ferlazzo and Foray: About the Space Pup project.

PMID- 28765379
TI  - Correction: Noninvasive In Vivo Imaging and Biologic Characterization of Thyroid
      Tumors by ImmunoPET Targeting of Galectin-3.

PMID- 28765377
TI  - Space radiobiology needs realistic hypotheses and relevant methodology.

PMID- 28765380
TI  - High-Expenditure Pharmaceutical Use Among Children in Medicaid.
AB  - BACKGROUND AND OBJECTIVES: Medication use may be a target for quality
      improvement, cost containment, and research. We aimed to identify medication
      classes associated with the highest expenditures among pediatric Medicaid
      enrollees and to characterize the demographic, clinical, and health service use
      of children prescribed these medications. METHODS: Retrospective, cross-sectional
      study of 3 271 081 Medicaid-enrolled children. Outpatient medication spending
      among high-expenditure medication classes, defined as the 10 most expensive among
      261 mutually exclusive medication classes, was determined by using transaction
      prices paid to pharmacies by Medicaid agencies and managed care plans among
      prescriptions filled and dispensed in 2013. RESULTS: Outpatient medications
      accounted for 16.6% of all Medicaid expenditures. The 10 most expensive
      medication classes accounted for 63.9% of all medication expenditures. Stimulants
      (amphetamine-type) accounted for both the highest proportion of expenditures
      (20.6%) and days of medication use (14.0%) among medication classes. Users of
      medications in the 10 highest-expenditure classes were more likely to have a
      chronic condition of any complexity (77.9% vs 41.6%), a mental health condition
      (35.7% vs 11.9%), or a complex chronic condition (9.8% vs 4.3%) than other
      Medicaid enrollees (all P < .001). The 4 medications with the highest spending
      were all psychotropic medications. Polypharmacy was common across all high
      expenditure classes. CONCLUSIONS: Medicaid expenditure on pediatric medicines is
      concentrated among a relatively small number of medication classes most commonly
      used in children with chronic conditions. Interventions to improve medication
      safety and effectiveness and contain costs may benefit from better delineation of
      the appropriate prescription of these medications.

PMID- 28765383
TI  - Vitamin D and dementia risk: the cause and consequence story.

PMID- 28765382
TI  - Health Care Expenditures and Utilization for Children With Noncomplex Chronic
      Disease.
AB  - BACKGROUND: Pediatric health care expenditures and use vary by level of
      complexity and chronic illness. We sought to determine expenditures and use for
      children with noncomplex chronic diseases (NC-CDs). METHODS: We performed a
      retrospective, cross-sectional analysis of Medicaid enrollees (ages 0-18 years)
      from January 1, 2012, through December 31, 2013, using administrative claims (the
      Truven MarketScan Medicaid Database). Patients were categorized by chronicity of
      illness by using 3M Health Information System's Clinical Risk Groups (CRGs) as
      follows: without chronic diseases (WO-CDs) (CRG 1-2), NC-CDs (CRG 3-5), and
      complex chronic diseases (C-CDs) (CRG 6-9). Primary outcomes were medical
      expenditures, including total annualized population expenditure and per-member
      per-year expenditure (PMPY). Secondary outcomes included the number of health
      care encounters over the 2-year period. RESULTS: There were 2 424 946 children
      who met inclusion criteria, 53% were WO-CD; 36% had an NC-CD; and 11% had a C-CD.
      Children with NC-CDs accounted for 33% ($2801 PMPY) of the annual spending
      compared with 20% ($1151 PMPY) accounted for by children WO-CDs and 47% ($12 569
      PMPY) by children with C-CDs. The median outpatient visit count by group over the
      2-year period was 15 (interquartile range [IQR] 10-25) for NC-CD, 8 (IQR 5-13) WO
      CD, and 34 (IQR 19-72) for C-CD. CONCLUSIONS: Children with NC-CDs accounted for
      33% of pediatric Medicaid expenditures and have significantly higher PMPY and
      aggregate annual expenditures than children WO-CDs. The annual aggregate
      expenditures of the NC-CD group represent a significant societal cost because of
      the high volume of children, extrapolated to ~$34.9 billion annually in national
      Medicaid expenditures.

PMID- 28765381
TI  - Characteristics of Children Enrolled in Medicaid With High-Frequency Emergency
      Department Use.
AB  - BACKGROUND AND OBJECTIVES: Some children repeatedly use the emergency department
      (ED) at high levels. Among Medicaid-insured children with high-frequency ED use
      in 1 year, we sought to describe the characteristics of children who sustain high
      frequency ED use over the following 2 years. METHODS: Retrospective longitudinal
      cohort study of 470 449 Medicaid-insured children appearing in the MarketScan
      Medicaid database, aged 1-16 years, with >=1 ED discharges in 2012. Children with
      high ED use in 2012 (>=4 ED discharges) were followed through 2014 to identify
      characteristics associated with sustained high ED use (>=8 ED discharges in 2013
      2014 combined). A generalized linear model was used to identify patient
      characteristics associated with sustained high ED use. RESULTS: A total of 39 945
      children (8.5%) experienced high ED use in 2012, accounting for 25% of total ED
      visits in 2012. Sixteen percent of these children experienced sustained high ED
      use in the following 2 years. Adolescents (adjusted odds ratio [aOR]: 1.4 [95%
      confidence interval: 1.3-1.5]), disabled children (aOR: 1.3 [95% confidence
      interval: 1.1-1.5]), and children with 3 or more chronic conditions (aOR: 2.1,
      [95% confidence interval: 1.9-2.3]) experienced the highest likelihood for
      sustaining high ED use. CONCLUSIONS: One in 6 Medicaid-insured children with high
      ED use in a single year experienced sustained high levels of ED use over the next
      2 years. Adolescents and individuals with multiple chronic conditions were most
      likely to have sustained high rates of ED use. Targeted interventions may be
      indicated to help reduce ED use among children at high risk.

PMID- 28765385
TI  - Vitamin D and incident dementia and cognitive impairment.

PMID- 28765384
TI  - Reply to Y Mao and H Yu.

PMID- 28765386
TI  - Reply to WB Grant.

PMID- 28765387
TI  - Modulation of postprandial glycemic responses by noncarbohydrate nutrients
      provides novel approaches to the prevention and treatment of type 2 diabetes.

PMID- 28765388
TI  - Muscle adjustment methods may affect the association of muscle mass with novel
      dietary protein food clusters.

PMID- 28765389
TI  - Reply to D Trico and A Natali.

PMID- 28765390
TI  - Reply to G Bahat and MA Karan.

PMID- 28765391
TI  - Effect of macronutrients on the glycemic index.

PMID- 28765392
TI  - Reply to TMS Wolever.

PMID- 28765393
TI  - Gaskins et al. study reports on a new opportunity for breast cancer prevention.

PMID- 28765394
TI  - Reply to AT Wijayabahu.

PMID- 28765395
TI  - Erratum for Maki et al. Consumption of a cranberry juice beverage lowered the
      number of clinical urinary tract infection episodes in women with a recent
      history of urinary tract infection. Am J Clin Nutr 2016;103:1434-42.

PMID- 28765396
TI  - Erratum for Karl et al. Substituting whole grains for refined grains in a 6-wk
      randomized trial favorably affects energy-balance metrics in healthy men and
      postmenopausal women. Am J Clin Nutr 2017;105:589-99.

PMID- 28765399
TI  - Retraction: Targeting Small Cell Lung Cancer Harboring PIK3CA Mutation with a
      Selective Oral PI3K Inhibitor PF-4989216.

PMID- 28765401
TI  - The ageing population in healthcare: a challenge to, and in, the workforce.

PMID- 28765400
TI  - Induction of IAPP amyloid deposition and associated diabetic abnormalities by a
      prion-like mechanism.
AB  - Although a large proportion of patients with type 2 diabetes (T2D) accumulate
      misfolded aggregates composed of the islet amyloid polypeptide (IAPP), its role
      in the disease is unknown. Here, we show that pancreatic IAPP aggregates can
      promote the misfolding and aggregation of endogenous IAPP in islet cultures
      obtained from transgenic mouse or healthy human pancreas. Islet homogenates
      immunodepleted with anti-IAPP-specific antibodies were not able to induce IAPP
      aggregation. Importantly, intraperitoneal inoculation of pancreatic homogenates
      containing IAPP aggregates into transgenic mice expressing human IAPP
      dramatically accelerates IAPP amyloid deposition, which was accompanied by
      clinical abnormalities typical of T2D, including hyperglycemia, impaired glucose
      tolerance, and a substantial reduction on beta cell number and mass. Finally,
      induction of IAPP deposition and diabetic abnormalities were also induced in vivo
      by administration of IAPP aggregates prepared in vitro using pure, synthetic
      IAPP. Our findings suggest that some of the pathologic and clinical alterations
      of T2D might be transmissible through a similar mechanism by which prions
      propagate in prion diseases.

PMID- 28765402
TI  - Monitoring risk factors of cardiovascular disease in cancer survivors.
AB  - There exist published literature for cardiovascular disease (CVD) risk monitoring
      in cancer survivors but the extent of monitoring in clinical oncology practice is
      unknown. We performed an interactive survey at a Royal College of Physicians
      conference (11 November 2016) attended by practitioners with an interest in late
      effects of cancer treatment and supplemented the survey with an audit among 32
      lung cancer survivors treated at St Peter's NHS Hospital in 2012-2016. Among the
      practitioners, 40% reported CVD risk monitoring performed at least annually,
      which is compatible with European Group for Blood and Marrow Transplantation
      Guidelines, but 31% indicated that monitoring was never performed. In contrast,
      77% felt that at least an annual assessment was required (p<0.001). Corroborating
      these data, among the lung cancer survivors, 31% and 16% had lipids or
      glucose/HbA1C measured annually, and 28% and 31% had never had these tests
      performed since their cancer treatment. Alerting healthcare providers to review
      protocols may help reduce CVD after cancer treatments.

PMID- 28765403
TI  - A hyperacute neurology team - transforming emergency neurological care.
AB  - We present the results of an 18-month study of a new model of how to care for
      emergency neurological admissions. We have established a hyperacute neurology
      team at a single district general hospital. Key features are a senior acute
      neurology nurse coordinator, an exclusively consultant-delivered service, acute
      epilepsy nurses, an acute neurophysiology service supported by neuroradiology and
      acute physicians and based within the acute medical admissions unit. Key
      improvements are a major increase in the number of patients seen, the speed with
      which they are seen and the percentage seen on acute medical unit before going to
      the general wards. We have shown a reduced length of stay and readmission rates
      for patients with epilepsy. Epilepsy accounted for 30% of all referrals. The cost
      implications of running this service are modest. We feel that this model is
      worthy of widespread consideration.

PMID- 28765404
TI  - Evaluation of feedback given to trainees in medical specialties.
AB  - The aim of this study was to evaluate the quality of feedback provided to
      specialty trainees (ST3 or higher) in medical specialties during their workplace
      based assessments (WBAs). The feedback given in WBAs was examined in detail in a
      group of 50 ST3 or higher trainees randomly selected from those taking part in a
      pilot study of changes to the WBA system conducted by the Joint Royal Colleges of
      Physicians Training Board. They were based in Health Education Northeast
      (Northern Deanery) and Health Education East of England (Eastern Deanery).
      Thematic analysis was used to identify commonly occurring themes. Feedback was
      mainly positive but there were differences in quality between specialties.
      Problems with feedback included insufficient detail, such that it was not
      possible to map the progression of the trainee, insufficient action plans made
      and the timing of feedback not being contemporaneous (feedback not being given at
      the time of assessment). Recommendations included feedback should be more
      specific; there need to be more options in the feedback forms for the supervisor
      to compare the trainee's performance to what is expected and action plans need to
      be made.

PMID- 28765405
TI  - Continuing professional development and Irish hospital doctors: a survey of
      current use and future needs.
AB  - Doctors rate clinical relevance and applicability as the most important
      determinants of continuing professional development (CPD) course selection. This
      study examined patterns of current CPD practice and perceived CPD needs among
      hospital doctors in Ireland across various clinical specialties. A cross
      sectional survey was administered to doctors, focusing on the areas of training
      needs analysis, CPD course content and preferred course format. In total, 547
      doctors identified doctor-patient communication as the skill ranked highest for
      importance and level of current performance. Workload/time organisation and
      stress management were areas where a skills deficiency was identified. Non
      clinical CPD topics, including resilience training, management and communication
      skills, were preferred areas for future CPD offerings. All respondents favoured
      interactive, hands-on sessions. CPD course completion and preference patterns
      differed significantly across clinical specialties. These results highlight the
      importance of considering the individual needs and preferences of clinicians
      across clinical specialties to facilitate more effective CPD programmes.

PMID- 28765406
TI  - A contemporary review of peripartum cardiomyopathy.
AB  - Peripartum cardiomyopathy reflects the presence of cardiac failure in the absence
      of determinable heart disease and occurs in late third trimester of pregnancy or
      up to 6 months postpartum. A full understanding of pathophysiological mechanisms
      is lacking, but excess prolactin levels, haemodynamic alterations, inflammation
      and nutritional deficiencies have all been implicated. Its clinical presentation
      has distinct overlap with physiological alterations in healthy pregnancy and this
      presents a diagnostic challenge. However, echocardiography can provide
      significant benefit in accurate assessment and narrowing of differentials.
      Pharmacotherapy is broadly aligned with established guidelines for cardiac
      failure, but specific therapies are indicated for treatment of clinical sequelae.
      Moreover, an individualistic approach is required based on clinical context to
      manage delivery. Further research appears imperative to optimise management
      strategies and reduce disease burden.

PMID- 28765407
TI  - Idiopathic inflammatory myopathies - a guide to subtypes, diagnostic approach and
      treatment.
AB  - The idiopathic inflammatory myopathies are a group of conditions characterised by
      inflammation of muscles (myositis) and other body systems. The diagnosis can be
      challenging because of the many potential clinical features and extra-muscular
      manifestations, which may be seemingly unrelated. An accurate diagnosis requires
      up-to-date understanding of the clinical manifestations, different clinical
      subtypes and appropriate interpretation of investigations, including newly
      described serological subtypes.This review will detail the approach to the
      diagnosis of an idiopathic inflammatory myopathy, based on up-to-date knowledge.
      The recently updated classification criteria and treatment options will also be
      described.

PMID- 28765408
TI  - When laboratory tests can mislead even when they appear plausible.
AB  - A laboratory test has three phases, pre-analytical, analytical and post
      analytical. The purpose of this review is to highlight an issue concerning the
      analytical phase of one of the most widely deployed groups of in vitro diagnostic
      tests using a common technology - namely immunoassay.Immunoassay entails an
      inherently high error rate and, therefore, has the potential for inaccurate and
      misleading results susceptible to misinterpretation and/or diagnostic
      misapplication by clinicians. An approach based on Bayesian inference (without
      mathematics or equations) - illustrated by examples - is presented; this may help
      clinicians in discerning potentially erroneous results even when they appear
      plausible and not unreasonable.Essentially, false positive results are most
      likely to occur when the disease prevalence/incidence is low. False negative
      results become more prominent when the prevalence/incidence of disease increases.
      When concern is raised, available follow-up laboratory tests should be initiated
      to establish with confidence the diagnostic reliability or unreliability of such
      results.

PMID- 28765409
TI  - The UK's multidisciplinary response to an Ebola epidemic.
AB  - The West African Ebola virus disease (EVD) epidemic was the largest and most
      devastating outbreak of EVD the world has ever seen. Its impact was felt far from
      the shores of Guinea, Liberia and Sierra Leone, with public health systems and
      clinicians across the globe confronted with an international response both in the
      affected region and within their own borders. The UK had a prominent role in
      response efforts, particularly in Sierra Leone. This article highlights how UK
      academic, health service, military, commercial and public health professionals
      all played a significant role both at home and abroad.

PMID- 28765410
TI  - Hypertension - state of the art 2017.

PMID- 28765412
TI  - Corrigendum: Portal vein thrombosis - a primer for the general physician.

PMID- 28765411
TI  - Heart failure - what's new and what's changed?
AB  - Physicians responsible for the care of patients with heart failure due to left
      ventricular systolic dysfunction have access to a broad range of evidence-based
      treatments that prolong life and reduce symptoms. In spite of the significant
      progress made over the last four decades, there is an ongoing need for novel
      therapies to treat a condition that is associated with stubbornly high morbidity
      and mortality. In this article, we discuss the findings of SERVE-HF, a randomised
      controlled trial of adaptive servo-ventilation in patients with left ventricular
      systolic dysfunction, as well as EMPA-REG, a study of the effects of a novel
      diabetic agent that may be of greater interest to heart failure specialists than
      diabetologists. We also examine further analyses of the groundbreaking PARADIGM
      HF trial, which attempt to answer some of the unresolved questions from the
      original study of the first combined angiotensin-receptor blocker and neprilysin
      inhibitor, sacubitril valsartan. The recently published National Institute for
      Health and Care Excellence guidelines for the management of acute heart failure
      and plans to introduce best practice tariffs bring into focus the need for well
      organised, multidisciplinary care. We discuss the challenges involved in
      developing and delivering a specialist service that meets the needs of a growing
      population of patients living with heart failure.

PMID- 28765413
TI  - Corrigendum: Drug therapy in anticoagulation: which drug for which patient?

PMID- 28765414
TI  - Acute geriatrics at the front door.
AB  - Older people with frailty and urgent care needs are major uses of health and
      social care services. Comprehensive geriatric assessment (CGA) is an evidence
      based approach to improving their outcomes, as well as improving service
      outcomes. Geriatricians form a small proportion of the overall workforce and
      cannot address the population need alone, so all clinicians (doctors, nurses,
      therapists and so on) need to engage in delivering CGA as a process of care,
      underpinned by specific competencies - which can be developed. Delivery of this
      care pathway needs to be measured and improved as rigorously as campaigns like
      those for improving sepsis or eradicating methicillin-resistant Staphylococcus
      aureus.

PMID- 28765415
TI  - Making difficult decisions with older patients on medical wards.
AB  - Decision making with older people can be difficult because of medical complexity,
      uncertainty (about prognosis, treatment effectiveness and priorities),
      difficulties brought by cognitive and communication impairment and the multiple
      family and other stakeholders who may need to be involved. The usual approach,
      based on balancing benefits and burdens of a treatment, and then deciding on the
      basis of autonomy (or best interests for someone lacking mental capacity), within
      the constraints of resources and equity, remains valid, but is often inadequate.
      In addition, approaches relying on optimal communication and relationship
      building and professional virtues are important. Older people vary in their
      medical status, views and preferences more than younger people and these
      variations must be sought and accommodated, using a shared decision-making
      approach. This includes adapting to the increasing numbers of people from
      different cultures.

PMID- 28765416
TI  - The physician's role in perioperative management of older patients undergoing
      surgery.
AB  - Life-sustaining and life-improving surgical interventions are increasingly
      available to older, frailer patients, many of whom have multimorbidity.
      Physicians can help support perioperative multidisciplinary teams with assessment
      and preoperative optimisation of physiological reserve, comorbidities and
      associated geriatric syndromes. Similar structured support can be useful in the
      postoperative period where older patients are at increased risk of delirium,
      medical complications, increased functional dependency and where discharge
      planning can prove more difficult than in younger cohorts. Comprehensive
      geriatric assessment has been shown to improve outcomes and is now embedded in
      most UK-based services for traumatic hip fracture. Perioperative comprehensive
      geriatric assessment has been explored in other surgical disciplines and
      procedures and, where evaluated, has been associated with improved outcomes. The
      need to support older patients with frailty undergoing surgery exceeds the
      capacity of specialist geriatricians. Other groups of healthcare professionals
      need to nurture the core competencies to support this group perioperatively.

PMID- 28765417
TI  - Prevention of falls in hospital.
AB  - Falls among inpatients are the most frequently reported safety incident in NHS
      hospitals. 30-50% of falls result in some physical injury and fractures occur in
      1-3%. No fall is harmless, with psychological sequelae leading to lost
      confidence, delays in functional recovery and prolonged hospitalisation. Yet
      falls are not true accidents and there is evidence that a coordinated
      multidisciplinary clinical team approach can reduce their incidence.
      Identification of multiple underlying risk factors coupled with clear
      interventions to ameliorate the impact of each has been shown to reduce the
      incidence of inpatient falls by 20-30%. The implementation of complex
      multiprofessional interventions is challenging and successful schemes seek to
      nurture a culture of vigilant safety consciousness in all staff at the clinical
      interface. Strong leadership and organisational oversight help to combine this
      cultural evolution with relevant evidence and rigorous measurement of performance
      in order to improve patient safety. The results of national audit suggest that
      NHS acute hospitals could do more to reduce the incidence of falls among
      inpatients.

PMID- 28765418
TI  - The emergence of sarcopenia as an important entity in older people.
AB  - Sarcopenia refers to the loss of muscle mass and strength seen with advancing
      age. The pathophysiology is multifactorial, with loss of muscle satellite cells,
      changes in hormonal systems, chronic inflammation, oxidative stress and anabolic
      resistance to protein utilisation all implicated. Older age, female sex and
      immobility are important risk factors. Sarcopenia is clinically important as it
      is a major risk factor for physical frailty, falls, prolonged hospitalisation,
      dependency and earlier death. Diagnosis requires evidence of reduced muscle mass
      measured by handgrip strength or walk speed, together with evidence of low muscle
      mass, measured by one of a variety of techniques such as bioimpedance analysis or
      dual X-ray absorptiometry. Resistance training is the only intervention of proven
      efficacy to treat sarcopenia, but a range of nutritional and pharmacological
      interventions are under test, including myostatin inhibitors, leucine and protein
      supplementation, angiotensin-converting enzyme inhibitors and allopurinol.

PMID- 28765419
TI  - CME Geriatric medicine (113041): self-assessment questionnaire.

PMID- 28765420
TI  - Lesson of the month 1: Large vessel vasculitis - a diagnostic challenge and the
      role of 18-fluorodeoxyglucose positron emission tomography.
AB  - Large vessel vasculitis can pose a significant diagnostic challenge. It may be
      insidious in onset with the only presenting symptoms consisting of constitutional
      compromise. It may mimic other pathologies and the only serological abnormalities
      may be abnormal inflammatory markers. Conventional imaging modalities may not be
      diagnostic. We present a case of large vessel vasculitis that proved a
      significant diagnostic challenge with diagnosis established on 18F
      fluorodeoxyglucose positron emission tomography (18F-FDG PET) computerised
      tomography (CT) imaging. This is one of five cases of large vessel vasculitis
      that were diagnosed in the rheumatology department at our trust over a 12-month
      period with diagnosis established with the use of 18F-FDG PET CT. We discuss the
      advantages of 18F-FDG PET CT over more conventional imaging modalities in
      diagnosing large vessel vasculitis.

PMID- 28765421
TI  - Lesson of the month 2: Dry skin, yellow nails and breathlessness.
AB  - Interstitial lung disease (ILD) is a common clinical problem, representing a
      group of diseases consisting of inflammation and progressive fibrosis of the
      lung. In some cases, an underlying cause is not identified; however, a
      significant proportion of ILD is associated with connective tissue disease (CTD).
      A detailed history and examination is the most important part of the assessment
      of patients with suspected ILD and will direct further investigation. This case
      illustrates the importance of identifying the symptoms and signs of CTD when
      assessing a patient with ILD. In addition, we describe an unusual presenting
      manifestation of yellow nails, which is not a recognised feature of CTD-ILD, but
      improved following immunomodulatory treatment for the overall condition.

PMID- 28765422
TI  - Image of the month: 'Diagnostic hands': Janeway lesions.

PMID- 28765423
TI  - Oncology admissions to the intensive care unit: what factors should influence the
      decision?

PMID- 28765424
TI  - Acute kidney injury associated with foot osteomyelitis.

PMID- 28765425
TI  - Testing for blood-borne viruses after a needle-stick injury in patients who lack
      the capacity to consent.

PMID- 28765426
TI  - Sodium glucose co-transporter 2 inhibitors successfully attenuated seasonal
      change of glycated haemoglobin A1c.

PMID- 28765427
TI  - Poor knowledge of safety aspects of long-term steroid use among patients and
      healthcare professionals.

PMID- 28765428
TI  - Sleep awareness and education among clinical practitioners.

PMID- 28765429
TI  - Delirium: a guide for the general physician.

PMID- 28765430
TI  - The new UK internal medicine curriculum.

PMID- 28765431
TI  - The latest national clinical guideline for stroke.

PMID- 28765432
TI  - Getting to the heart of hypopituitarism.

PMID- 28765433
TI  - Imaging in Parkinson's disease.

PMID- 28765435
TI  - Times Are A-Changin'.

PMID- 28765434
TI  - A choroid plexus papilloma manifesting as anorexia nervosa in an adult.

PMID- 28765436
TI  - Predoctoral Teaching of Geriatric Dentistry in U.S. Dental Schools.
AB  - The aim of this study was to assess the current teaching of geriatric dentistry
      in U.S. dental schools and compare the findings to previous reports. Academic
      deans at all 67 U.S. dental schools were contacted in November 2015 via email,
      asking them to complete a questionnaire about the teaching of geriatric dentistry
      or gerodontology at their institution. Questionnaires were received from 56 of
      the 67 schools (84% response rate). The results showed that geriatric dentistry
      was taught in all responding schools; for 92.8% of the respondents, the
      instruction was compulsory. Among the responding schools, 62.5% were teaching it
      as an independent course, 25% as an organized series of lectures, and 8.9% as
      occasional lectures in parts of other courses. In addition, 57.1% had some form
      of compulsory clinical education in geriatric dentistry. Public schools, as
      opposed to private schools, were marginally associated with an increased interest
      in expanding geriatric dentistry teaching (p=0.078). No differences were found
      between any teaching variables and school location. This study found that the
      form of education in geriatric dentistry in U.S. dental schools differed in many
      ways, but the teaching of geriatric dentistry had increased among all respondents
      and had been increasing for over 30 years. Future research is needed to determine
      the impact of this teaching on services to the geriatric community.

PMID- 28765437
TI  - Humanism in Dental Education: A Comparison of Theory, Intention, and Stakeholder
      Perceptions at a North American Dental School.
AB  - In today's dental education environment, a humanistic culture is an expectation
      for all U.S. dental schools, codified in 2013 by its inclusion in the Commission
      on Dental Accreditation's standards for accreditation. The University of the
      Pacific Arthur A. Dugoni School of Dentistry has made an active commitment to
      humanism since the mid-1970s. The aim of this study was to determine how well the
      school's students and faculty and staff members perceived the school was living
      up to its formal aspirational values and who was benefitting from the humanistic
      culture. Using an electronic survey, data were collected from a total of 195
      students, faculty members, and staff members in 2014. Respondents were 15% of the
      492 full- and part-time faculty members; 9% of the total student population of
      540; and 29% of 255 staff members. In the responses, humanism was described as
      manifest by attributes such as caring, understanding, respect, and compassion.
      Although the findings confirmed the value of a humanistic culture, some portions
      of the school's formal definition and goals, such as good work ethic,
      professional responsibility, high ethical standards, increasing independence, and
      attainment of competence, appeared less frequently in responses. Authentic
      assessment of institutional culture proved challenging. Focus groups offered
      additional ways to assess how effectively the school lives its core value of
      humanism. There was recognition that more varied, robust methods were needed to
      assess institutional alignment with stated goals for a humanistic learning
      environment.

PMID- 28765438
TI  - Dental Faculty Members' Pedagogic Beliefs and Curriculum Aims in Problem-Based
      Learning: An Exploratory Study.
AB  - The aims of this exploratory study were to explore dental faculty members' views
      and beliefs regarding knowledge, the dental profession, and teaching and learning
      and to determine how these views related to their problem-based learning (PBL)
      instructional practices. Prior to a PBL in dental education conference held in
      2011, all attendees were invited to complete a survey focused on their
      pedagogical beliefs and practices in PBL. Out of a possible 55 participants, 28
      responded. Additionally, during the conference, a forum was held in which
      preliminary survey findings were shared and participants contributed to focus
      group data collection. The forum results served to validate and bring deeper
      understanding to the survey findings. The conference participants who joined the
      forum (N=32) likely included some or many of the anonymous respondents to the
      survey, along with additional participants interested in dental educators'
      beliefs. The findings of the survey and follow-up forum indicated a disconnect
      between dental educators' reported views of knowledge and their pedagogical
      practices in a PBL environment. The results suggested that the degree of
      participants' tolerance of uncertainty in knowledge and the discrepancy between
      their epistemological and ontological beliefs about PBL pedagogy influenced their
      pedagogical choices. These findings support the idea that learner-centered,
      inquiry-based pedagogical approaches such as PBL may create dissonance between
      beliefs about knowledge and pedagogical practice that require the building of a
      shared understanding of and commitment to curricular goals prior to
      implementation to ensure success. The methods used in this study can be useful
      tools for faculty development in PBL programs in dental education.

PMID- 28765439
TI  - Will a Short Training Session Improve Multiple-Choice Item-Writing Quality by
      Dental School Faculty? A Pilot Study.
AB  - Faculty members are expected to write high-quality multiple-choice questions
      (MCQs) in order to accurately assess dental students' achievement. However, most
      dental school faculty members are not trained to write MCQs. Extensive faculty
      development programs have been used to help educators write better test items.
      The aim of this pilot study was to determine if a short workshop would result in
      improved MCQ item-writing by dental school faculty at one U.S. dental school. A
      total of 24 dental school faculty members who had previously written MCQs were
      randomized into a no-intervention group and an intervention group in 2015. Six
      previously written MCQs were randomly selected from each of the faculty members
      and given an item quality score. The intervention group participated in a
      training session of one-hour duration that focused on reviewing standard item
      writing guidelines to improve in-house MCQs. The no-intervention group did not
      receive any training but did receive encouragement and an explanation of why good
      MCQ writing was important. The faculty members were then asked to revise their
      previously written questions, and these were given an item quality score. The
      item quality scores for each faculty member were averaged, and the difference
      from pre-training to post-training scores was evaluated. The results showed a
      significant difference between pre-training and post-training MCQ difference
      scores for the intervention group (p=0.04). This pilot study provides evidence
      that the training session of short duration was effective in improving the
      quality of in-house MCQs.

PMID- 28765440
TI  - Teaching Cultural Competence in Dental Education: A Systematic Review and
      Exploration of Implications for Indigenous Populations in Australia.
AB  - Indigenous and other minority populations worldwide experience higher rates of
      disease including poor oral health than other populations. Cultural competence of
      practitioners is increasingly being recognized as fundamental to health care and
      quality of life in addressing these disparities. The aims of this study were to
      conduct a systematic review of the literature about teaching cultural competence
      in dental education and to explore the particular relevance of that teaching for
      the oral health care of Indigenous populations in Australia. A systematic review
      employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) statement was conducted of published studies that explored cultural
      competency interventions in dental curricula. A total of 258 studies from 2004 to
      2015 were identified; after removing duplications and applying criteria for
      exclusion, 12 were selected for analysis, involving 1,360 participants. The
      principal themes identified in the qualitative analysis of these studies were
      curriculum content, curriculum delivery, community service-learning, reflective
      writing, and evaluation. Students need knowledge of health disparities and
      community health to better understand the perspectives of culturally diverse
      populations and to communicate effectively with people from various cultures. The
      principal strategies that improved cultural competence in the articles examined
      in this study were educational seminars, community service-learning, and
      reflective writing. These findings suggest that integration of cultural
      competency curricula using a combination of didactic or online training,
      community engagement, and reflective writing may increase the cultural knowledge
      and skills of dental students.

PMID- 28765441
TI  - Effect of Faculty Development Activities on Dental Hygiene Faculty Perceptions of
      and Teaching About Motivational Interviewing: A Pilot Study.
AB  - The aims of this pilot study were to assess dental hygiene faculty members'
      perceptions of the importance of motivational interviewing (MI) and their
      confidence in teaching students about MI and to determine the effect of MI
      training sessions on those perceptions. Participants were a convenience sample of
      all 16 dental hygiene faculty members who teach in the clinic at the University
      of Michigan School of Dentistry. Participants' perceptions were assessed prior to
      a workshop in MI (pretest), immediately after the workshop (posttest 1), and
      eight months after the workshop, at the end of the academic year (posttest 2).
      During the same period, some of the workshop participants took part in team
      grading sessions of audio recordings of student-patient MI interactions. The
      results showed that the majority of the faculty members perceived it was
      important to personally embrace the overall spirit of MI during patient care, and
      they were confident supporting students as well. Their ratings for embracing the
      spirit of MI increased from pretest to posttest 1, but slightly decreased at
      posttest 2. This trend was also seen in their assessment of the importance of and
      their confidence in teaching the eight MI strategies over time. Among the
      workshop participants, 56% were part of team grading; they reported the most
      helpful professional development activities overall were team grading (58%) and
      the workshop (25%). These results suggest the importance of making use of a
      variety of faculty development activities and of introducing appropriate follow
      up to training sessions over time to ensure long-lasting effects. Future research
      using carefully designed, multi-institution, longitudinal studies is needed to
      determine the most effective ways to prepare dental hygiene faculty members to
      educate their students about MI.

PMID- 28765442
TI  - Critical Thinking Theory to Practice: Using the Expert's Thought Process as Guide
      for Learning and Assessment.
AB  - Critical thinking skills are essential for the successful dentist, yet few
      explicit skillsets in critical thinking have been developed and published in peer
      reviewed literature. The aims of this article are to 1) offer an assessable
      critical thinking teaching model with the expert's thought process as the
      outcome, learning guide, and assessment instrument and 2) offer three critical
      thinking skillsets following this model: for geriatric risk assessment,
      technology decision making, and situation analysis/reflections. For the objective
      component, the student demonstrates delivery of each step in the thought process.
      For the subjective component, the student is judged to have grasped the
      principles as applied to the patient or case. This article describes the
      framework and the results of pilot tests in which students in one year at this
      school used the model in the three areas, earning scores of 90% or above on the
      assessments. The model was thus judged to be successful for students to
      demonstrate critical thinking skillsets in the course settings. Students
      consistently delivered each step of the thought process and were nearly as
      consistent in grasping the principles behind each step. As more critical thinking
      skillsets are implemented, a reinforcing network develops.

PMID- 28765443
TI  - Integration of Digital Dentistry into a Predoctoral Implant Program: Program
      Description, Rationale, and Utilization Trends.
AB  - A recently revised predoctoral implant curriculum at the University of Illinois
      at Chicago College of Dentistry integrated digital dentistry into both the
      preclinical dental implant course and clinical activities. Traditionally,
      competence in the didactic and clinical parts of predoctoral education in single
      tooth implant restorations has emphasized the analog impression technique and
      subsequent mounting of soft tissue working casts. However, computer-aided
      design/computer-aided manufacturing (CAD/CAM) implant restorations can play a
      significant role in predoctoral dental education utilizing digital technologies.
      The goal of the curriculum expansion is to transition from analog to partially
      digital and, finally, complete digital workflow. The aim of this article is to
      describe the specific components, implementation, and rationale for the new
      digitally integrated implant curriculum and present short-term clinical
      utilization trends.

PMID- 28765444
TI  - An Interactive Online Approach to Teaching Evidence-Based Dentistry with Web 2.0
      Technology.
AB  - At many dental schools, evidence-based dentistry (EBD) is taught in a traditional
      lecture format. To avoid the constraints of lectures, in 2012 the EBD unit was
      redesigned for online delivery at the Arthur A. Dugoni School of Dentistry at the
      University of the Pacific with a Web 2.0 tool called Voicethread. The aim of this
      study was to assess the impact of Voicethread-based online learning on students'
      perceptions of learning EBD, their participation and engagement, and their
      acceptance of this new online delivery approach. Students' perceptions were
      collected from two sources: a self-assessment quiz and a question on their self
      reported preparedness in EBD from the 2014 American Dental Education Association
      (ADEA) Survey of Dental School Seniors. The Voicethread analytics tool provided
      data on students' participation and engagement. Students' responses to the survey
      questions on the self-assessment quiz provided data on their acceptance of
      Voicethread-based learning. The average score of the 124 students (91% of total)
      taking the quiz was 7.3 out of 8. The percentage of students who reported in the
      2014 ADEA survey that they were "well prepared" in EBD was 45.2%, compared with
      the national average of 31.2%. Responses to this question for the Classes of 2013
      and 2015, who received instruction in the traditional lecture format, were 35.2%
      and 34.6%, respectively. With Voicethread, students actively participated and
      interacted with their peers through questions and answers. They perceived
      Voicethread to be more effective than other delivery approaches and reported that
      it made learning more active and engaging. These findings suggest that
      Voicethread may be an effective tool for students to learn EBD since it adds
      interactivity to online learning.

PMID- 28765445
TI  - Current State of Dental Education: Executive Summary.
AB  - This executive summary for Section 1 of the "Advancing Dental Education in the
      21st Century" project provides a composite picture of information from 12
      background articles on the current state of dental education in the United
      States. The summary includes the following topics: the current status of the
      dental curriculum, the implications of student debt and dental school finances,
      the expansion of enrollment, student diversity, pre- and postdoctoral education,
      safety net status of dental school clinics, and trends in faculty.

PMID- 28765446
TI  - How Many Dentists Are Needed in 2040: Executive Summary.
AB  - Five background articles in Section 2 of the "Advancing Dental Education in the
      21st Century" project examined some of the factors likely to impact the number of
      dentists needed in 2040: 1) the oral health of the population, 2) changes in the
      utilization of dental services, 3) new technologies, 4) the growth of large
      capitated dental group practices, and 5) the demand for dental care. With this
      information, a sixth background article estimated the number of dentists needed
      in 2040 compared to the number expected if current trends continue. This
      executive summary provides an overview of findings from these six articles. The
      data indicate major improvements in oral health, especially in upper income
      groups that account for 65% of practice revenues. At the same time, per capita
      utilization of restorative and prosthetic services has declined dramatically. No
      major new technologies are likely to impact the need for dentists by 2040. In a
      large capitated group practice, full-time general dentists treated an average of
      2,100 patients per year; solo general dentists averaged 1,350. Based on the
      examined factors, growth in demand for traditional forms of care may slow
      substantially, raising the potential for a surplus of dentists in 2040. If these
      trends continue, the key national policy issue then would be: should schools
      reduce the number of graduates before market forces require them to downsize or
      close, or are other alternatives available?

PMID- 28765447
TI  - What Should Oral Health Professionals Know in 2040: Executive Summary.
AB  - The "Advancing Dental Education in the 21st Century" project assesses current
      status and trends to prepare for the future. Section 3 of the project asks what
      knowledge and skills should dental and advanced dental education learners have to
      provide dental care in 2040 and how should educators be preparing them. This
      executive summary of five background articles in this section focuses on
      predoctoral education, advanced dental education, the provision of medical
      services within dental practice, the incorporation of oral health services into
      primary care and medical practice, and interprofessional education and practice.
      The changing environment and external forces are presented along with their
      implications for advancing dental education. These forces include changes in
      population characteristics (e.g., demographics, disease prevalence, health
      disparities, consumerism), treatment needs and modalities, care delivery, science
      and technology, educational methods, and medical and dental integration. Future
      oral health professionals (OHPs) will care for more diverse patient populations,
      older patients with complex medical and dental needs, and relatively dentally
      healthy younger cohorts who require fewer complex restorative and prosthodontic
      treatments. Increasing integration of medical and oral health education and
      patient care will require OHPs to have more medical knowledge and to practice in
      intra- and interprofessional teams. OHPs increasingly will be providing patient
      centered care as employees in large group practices, health care settings, and
      safety net clinics with expanded types of OHPs and improved materials and
      technology. Educators need to implement innovative curricula and educational
      methods to prepare for and adapt to the disruptive changes that lie ahead.

PMID- 28765449
TI  - Trends in Financing Dental Education, 2004-05 to 2011-12.
AB  - This article examines dental school financial trends from 2004-05 to 2011-12,
      based on data from the American Dental Association (ADA) annual financial survey
      completed by all U.S. dental schools. For public schools, revenues from tuition
      and fees increased 68.6%, and state support declined 17.2% over the examined
      period. For private schools, revenues from tuition and fees increased 38.9%, and
      university indirect subsidies declined 77.9% over the same period. The major
      factors affecting dental school expenditures were the number of students and
      postdoctoral students, faculty practice, and research. The findings suggest that
      dental schools are now more dependent financially on tuition and fees than in the
      past. Schools have been able to pass on increases in operating costs to students
      and specialty postdoctoral students. Now that growth in dentists' incomes is
      slowing and student debt is at an all-time high, this financing strategy may not
      be sustainable in the long run. This article was written as part of the project
      "Advancing Dental Education in the 21st Century."

PMID- 28765450
TI  - The 21st-Century Dental Curriculum: A Framework for Understanding Current Models.
AB  - This article provides an overview of the emergence of professional education and
      academic dentistry, in particular into the comprehensive research university. The
      development of academic dentistry as a vital member of the academic health center
      at the research university and beyond is described. Summaries are provided of
      major studies and innovations in dental education models and curricula, ranging
      from the Gies report in 1926 to the 1995 Institute of Medicine study Dental
      Education at the Crossroads, the U.S. surgeon general's report on oral health in
      2000, the Macy study report in 2008, and the American Dental Education
      Association Commission on Change and Innovation in Dental Education (ADEA CCI)
      series of articles published from 2005 to 2009. The article also tracks changes
      in number and institutional affiliation of U.S. dental schools. This article was
      written as part of the project "Advancing Dental Education in the 21st Century."

PMID- 28765451
TI  - Ten-Year Student Trends in U.S. Dental Schools, 2004-05 to 2014-15.
AB  - This article provides an overview of the status of students applying to and
      enrolling in dental schools in the United States over a ten-year period from 2004
      05 to 2014-15. The data are mainly drawn from published reports of the American
      Dental Association (ADA) and American Dental Education Association (ADEA). This
      overview includes trends on tuition levels, diversity in enrollment, and debt
      levels of students upon graduation as well as students' satisfaction with their
      education. This article was written as part of the project "Advancing Dental
      Education in the 21st Century."

PMID- 28765452
TI  - Considering Students' Cost of a Dental Education: Return on Investment and Debt
      to Income Ratio.
AB  - The cost for students of a dental education has become an issue of concern. This
      article explores the return on investment and the debt to income ratio of
      studying dentistry. These two measures are monitored to gain perspective on
      whether the cost of education pays off in earnings. The factors underlying these
      measures and a discussion of them are included. The purpose of this article is to
      focus attention on one of the current issues facing dental schools in the United
      States. This article was written as part of the project "Advancing Dental
      Education in the 21st Century."

PMID- 28765453
TI  - Trends in Dental Faculty of U.S. Dental Schools, 2003-04 to 2013-14.
AB  - The aim of this article is to provide a general overview of trends impacting the
      faculty of U.S. dental schools. Data such as full- and part-time status, tenure
      status, student-faculty ratios, aging of the faculty, and compensation are
      reported for the period from 2003-04 to 2013-14. Data used are from the American
      Dental Association (ADA) and the American Dental Education Association (ADEA).
      The first part of the report describes general characteristics of faculty trends,
      and the second part provides an analysis of those trends. This article was
      written as part of the project "Advancing Dental Education in the 21st Century."

PMID- 28765454
TI  - Current Status of Postdoctoral and Graduate Programs in Dentistry.
AB  - Advanced dental education has evolved in the context of societal needs and
      economic trends to its current status. Graduate programs have positioned their
      role in the context of health systems and health science education trends in
      hospitals, interprofessional clinical care teams, and dental schools and oral
      health care systems. Graduate dental education has been a critical factor in
      developing teams in trauma care, craniofacial disorders, pediatric and adult
      medicine, and oncology. The misalignment of the mission of graduate dental
      programs and the demands of private practice has posed a challenge in the
      evolution of programs as educational programs have been directed towards tertiary
      and indigent care while the practice community focuses on largely healthy
      affluent patients for complex clinical interventions. Those seeking graduate
      dental education today are smaller in number and include more international
      dental graduates than in the past. Graduate dental education in general dentistry
      and in the nine recognized dental specialties now includes Commission on Dental
      Accreditation (CODA) recognition of training standards as part of its
      accreditation process and a CODA accreditation process for areas of clinical
      education not recognized as specialties by the American Dental Association.
      Current types of programs include fellowship training for students in recognized
      specialties. This article was written as part of the project "Advancing Dental
      Education in the 21st Century."

PMID- 28765455
TI  - Current Status of Operation and Management of Dental School Clinics.
AB  - This article summarizes the current status of the operation and management of
      dental school clinics as schools strive to provide excellent patient-centered
      care in an environment that is educationally sound, efficient, and financially
      strong. Clinical education is a large component of dental education and an area
      in which many dental schools have an opportunity to enhance revenue. Clinical
      efficiencies and alternative models of clinical education are evolving in U.S.
      dental schools, and this article describes some of those evolutionary changes.
      This article was written as part of the project "Advancing Dental Education in
      the 21st Century."

PMID- 28765456
TI  - Trends in Basic Sciences Education in Dental Schools, 1999-2016.
AB  - The purpose of this study was to examine data published over the past two decades
      to identify trends in the basic sciences curriculum in dental education, provide
      an analysis of those trends, and compare them with trends in the basic sciences
      curriculum in medical education. Data published from the American Dental
      Association (ADA) Surveys of Dental Education, American Dental Education
      Association (ADEA) Surveys of Dental School Seniors, and two additional surveys
      were examined. In large part, survey data collected focused on the structure,
      content, and instructional strategies used in dental education: what was taught
      and how. Great variability was noted in the total clock hours of instruction and
      the clock hours of basic sciences instruction reported by dental schools.
      Moreover, the participation of medical schools in the basic sciences education of
      dental students appears to have decreased dramatically over the past decade.
      Although modest progress has been made in implementing some of the curriculum
      changes recommended in the 1995 Institute of Medicine report such as integrated
      basic and clinical sciences curricula, adoption of active learning methods, and
      closer engagement with medical and other health professions education programs,
      educational effectiveness studies needed to generate data to support evidence
      based approaches to curriculum reform are lacking. Overall, trends in the basic
      sciences curriculum in medical education were similar to those for dental
      education. Potential drivers of curriculum change were identified, as was recent
      work in other fields that should encourage reconsideration of dentistry's
      approach to basic sciences education. This article was written as part of the
      project "Advancing Dental Education in the 21st Century."

PMID- 28765457
TI  - Trends in Behavioral Sciences Education in Dental Schools, 1926 to 2016.
AB  - This article outlines the journey of behavioral sciences education from a
      multidisciplinary array of topics to a discipline with a name, core identity, and
      mission in dental schools' curricula. While not exhaustive, it covers pivotal
      events from the time of the Gies report in 1926 to the present. Strengths and
      weaknesses of current behavioral sciences instruction in dental schools are
      discussed, along with identification of future opportunities and potential
      threats. Suggestions for future directions for behavioral sciences and new roles
      for behavioral sciences faculty in dental schools are proposed. This article was
      written as part of the project "Advancing Dental Education in the 21st Century."

PMID- 28765458
TI  - Looking Back to Move Ahead: Interprofessional Education in Dental Education.
AB  - Interprofessional education (IPE) is a widely recognized and critical component
      of dental and health professions education and is included in two of the
      predoctoral education standards required by the Commission on Dental
      Accreditation (CODA). Following a review of the literature on the state of IPE
      education in U.S. dental education programs, this article revisits six
      institutions identified in previous research as exemplars successfully
      implementing IPE on their campuses. Interviews were conducted with leaders at the
      following programs: Columbia University, Medical University of South Carolina,
      University of Colorado Anschutz Medical Campus, University of Florida, University
      of Minnesota, and Western University of Health Sciences. Strengths and weakness
      of IPE in dental education are discussed, along with opportunities for the future
      including reducing barriers to scheduling, increasing intraprofessional
      education, and consistent outcomes assessment. The article concludes with lessons
      learned by administrators and suggestions for improving incorporation of these
      requirements into predoctoral dental education programs by emphasizing the
      importance of IPE and dentistry's role in overall health. This article was
      written as part of the project "Advancing Dental Education in the 21st Century."

PMID- 28765459
TI  - Clinical and Community-Based Education in U.S. Dental Schools.
AB  - This review of U.S. dental schools' clinical curricula suggests that the basic
      structure of clinical education has not changed significantly in the past 60
      years, although important developments include the introduction of competency
      based education and community-based clinical education. Most dental schools still
      have a two-year preclinical curriculum and a two-year clinical curriculum, and
      most schools still operate a large clinical facility where students receive the
      bulk of their clinical education and assessment for graduation. In those clinics,
      dental students are the main providers of patient treatment, with faculty serving
      in supervisory roles. In addition, a major portion of the entire dental
      curriculum continues to be dedicated to student education on the restoration of a
      single tooth or replacement of teeth. This article was written as part of the
      project "Advancing Dental Education in the 21st Century."

PMID- 28765460
TI  - Are Dental Schools Part of the Safety Net?
AB  - This article examines the current safety net activities of dental schools and
      reviews strategies by which schools could care for more poor and low-income
      patients. The primary data come from the annual Survey of Dental Education, a
      joint American Dental Education Association (ADEA) and American Dental
      Association (ADA) activity. The analyses use descriptive statistics and are
      intended to give ballpark estimates of patients treated under varying clinical
      scenarios. Some 107.4 million people are underserved in comparison to utilization
      rates for middle-income Americans. In 2013-14, pre- and postdoctoral students
      treated about 1,176,000 disadvantaged patients. This is an estimate; the actual
      value may be 25% above or below this number. The impact of potential strategies
      for schools to provide more care to poor and low-income patients are discussed;
      these are larger class size, more community-based education, a required one-year
      residency program, and schools' becoming part of publicly funded safety net
      clinics. While dental schools cannot solve the access problem, they could have a
      major impact if the payment and delivery strategies discussed were implemented.
      This article was written as part of the project "Advancing Dental Education in
      the 21st Century."

PMID- 28765461
TI  - Trends in Oral Diseases in the U.S. Population.
AB  - This article reviews trends in dental caries, periodontal disease, and tooth loss
      for the United States along with population dynamics and risk factors that might
      influence these trends going forward. Dental caries experience remains high in
      the primary dentition. Caries severity in permanent teeth of children has
      declined to historically low levels, and long-standing inequalities in untreated
      caries appear to be narrowing. Declines in caries severity of children's
      permanent teeth have stabilized at a low level, but likely will contribute to
      future reductions in dental caries severity in adults. The prevalence of
      periodontal disease is high in adults, and only a small percentage have severe
      forms of the disease. Countervailing trends in determinants would suggest little
      change in the prevalence of periodontal disease in the future, but the lack of an
      obvious trend over the last two decades makes projections uncertain. Tooth loss
      as a consequence of dental disease has declined markedly over the last half
      century and has been all but eliminated in high-income groups. However, notable
      exceptions to these favorable trends are evident. Progress in prevention policies
      and programs that affect disease experience appears slower than progress in
      meeting population-level caries treatment needs. Clearly, long-standing
      inequities related to political and social determinants remain for all dental
      diseases, and income disparities in dental disease are widening for some
      indicators. Growing inequalities raise ethical and public health concerns that
      should be prominent in discussions of dental workforce needs and strategies for
      the next 25 years. This article was written as part of the project "Advancing
      Dental Education in the 21st Century."

PMID- 28765462
TI  - The Impact of Improved Oral Health on the Utilization of Dental Services.
AB  - Since the mid-20th century, there has been a remarkable decline in dental caries
      in the United States. The effects of that caries decline have now been
      demonstrated well into the adult population. These improvements in oral health
      are resulting in substantial declines in the reparative and restorative dental
      services being provided to the affected individuals, who comprise a growing part
      of the population. Because of fewer compromised teeth, extractions and their
      sequelae also are declining. Much of the recall and periodontal maintenance care
      can be provided by allied dental personnel. As the older age cohorts, who were
      children before the caries decline occurred, become an ever-smaller part of the
      population, the number of patients an individual dentist can treat in a year is
      likely to increase. This article was written as part of the project "Advancing
      Dental Education in the 21st Century."

PMID- 28765463
TI  - Dental Group Practice and the Need for Dentists.
AB  - This study compared the number of patients treated per year by general dentists
      and dental hygienists in solo practice and by those employed by a large group
      practice. Information on the annual number of patient visits to solo general
      dental practitioners comes from the 2013 American Dental Association (ADA) Survey
      of Dental Practice. Patient visits were divided by 2.5 to estimate the number of
      patients treated annually. The data on group practices come from HealthPartners
      (HP) of Minnesota, a large not-for-profit medical and dental Health Maintenance
      Organization that accepts insurance contracts based on global budgets and is
      financially at risk. In 2013, solo general dentists averaged 1,350 patients,
      while the average HP general dentist treated 2,052 patients. HP general dentists
      thus treated over 700 more patients annually than did solo practitioners. This
      large difference has major implications for the future of the dental delivery
      system and dental education. This article was written as part of the project
      "Advancing Dental Education in the 21st Century."

PMID- 28765464
TI  - The Effect of New Oral Care Technologies on the Need for Dentists in 2040.
AB  - This article addresses changes in technology of oral self-care or professional
      care that may increase or decrease the demand for dentists by 2040. The focus is
      on dental caries, periodontitis, and temporomandibular joint disorders (TMD), as
      the first two are the main areas of current practice and because TMD is an area
      for growth. To address this question, the authors examined the scientific
      literature and government registries to identify recent or soon-to-be-available
      technologies. They also examined the state of translational efficiency,
      dissemination, and adoption of advances into dental practice. The pipeline of
      applicable technology is limited. Nevertheless, between now and 2040, emerging
      technologies will continue to reduce the need for training more dentists, while
      no technologies are emerging that will significantly increase the need.
      Technology in dentistry is adopted slowly as is true in other medical
      specialties. If a breakthrough product did appear, the results of industry
      sponsored trials would be viewed skeptically by the profession, and considerable
      time would be required to establish the applicability of the findings to the
      broader population. Greater integration of dentistry into preventive medicine,
      with dentists offering point-of-service medical testing for systemic disease as
      suggested by the American Dental Association (ADA), would require a paradigm
      shift, can occur only over a lengthy period, and is unlikely to impact this
      assessment. This article was written as part of the project "Advancing Dental
      Education in the 21st Century."

PMID- 28765465
TI  - Projecting the Demand for Dental Care in 2040.
AB  - The purpose of this study was to provide a forward-thinking assessment of the
      underlying factors likely to impact trends in dental care demand and the need for
      dental providers in 2020, 2025, and beyond. Dental workforce trends and their
      likely impact on the need for dentists are a function of predicted dental care
      demand, which will in turn be determined by the size and characteristics of our
      population size, economic outlook, the state of public and private dental care
      insurance, trends in dental care delivery, professionally determined dental care
      need, and population health beliefs. Projecting rates of dental care utilization
      far into the future is difficult because projections must be made using
      historical data, and established trends may not persist if there is structural
      change in the future. Nonetheless, when structural change occurs, it does not
      typically affect all aspects of the economy, so there is value in describing the
      likely future impact of current trends. This article was written as part of the
      project "Advancing Dental Education in the 21st Century."

PMID- 28765466
TI  - Estimating the Number of Dentists Needed in 2040.
AB  - Numerous factors that underlie the need for dentists are undergoing significant
      changes. Three factors are especially important: 1) improvements in oral health;
      2) lower expenditures per patient per year, giving dentists the incentive to
      treat more patients to maintain incomes that justify their investment in dental
      education and practice; and 3) dental schools' producing new dentists at a faster
      rate than the growth in the population. If these trends continue, there is likely
      to be a dentist surplus of between 32% and 110% by 2040. A major challenge for
      dental schools is to adjust the production of dentists before 2040 and not wait
      for market forces to reduce the surplus. Whether there will be a painful market
      based solution to the problem, as there was in the 1980s, or whether a more
      orderly path can be found is one of the key challenges of the project "Advancing
      Dental Education in the 21st Century," for which this article was written.

PMID- 28765467
TI  - Dental Education Required for the Changing Health Care Environment.
AB  - To be able to meet the demands for care in 2040, dental graduates will need to
      address challenges resulting from the rapidly changing health care environment
      with knowledge and sets of skills to build on current standards and adapt to the
      future. The purposes of this article are to 1) analyze key challenges likely to
      evolve considerably between now and 2040 that will impact dental education and
      practice and 2) propose several sets of skills and educational outcomes necessary
      to address these challenges. The challenges discussed include changes in
      prevalence of oral diseases, dental practice patterns, materials and
      technologies, integrated medical-dental care, role of electronic health records,
      cultural competence, integrated curricula, interprofessional education, specialty
      general balance, and web/cloud-based collaborations. To meet these challenges,
      the dental graduate will need skills such as core knowledge in basic and clinical
      dentistry, technical proficiency, critical thinking skills for lifelong learning,
      ethical and professional values, ability to manage a practice, social
      responsibility, and ability to function in a collegial intra- and
      interprofessional setting. Beyond the skills of the individual dentist will be
      the need for leadership in academia and the practice community. Academic and
      professional leaders will need to engage key constituencies to develop strategic
      directions and agendas with all parties pointed toward high standards for
      individual patients and the public at large. This article was written as part of
      the project "Advancing Dental Education in the 21st Century."

PMID- 28765468
TI  - Trends in Generalist and Specialty Advanced Dental Education and Practice, 2005
      06 to 2015-16 and Beyond.
AB  - This article reviews the data on advanced dental education for the past decade
      and explores what advanced dental education might look like in the years leading
      up to 2040, including how its graduates will address the oral health needs of the
      population. The authors based these projections on published data about advanced
      dental education collected by the American Dental Association and other
      organizations. Nevertheless, a certain degree of speculation was involved. The
      article presents current data and trends in advanced dental education,
      environmental factors impacting advanced dental education, and lessons drawn from
      other areas of health care that support the potential scenarios that are
      described. This article was written as part of the project "Advancing Dental
      Education in the 21st Century."

PMID- 28765469
TI  - The Future of Oral Health Care Provided by Physicians and Allied Professionals.
AB  - Medical providers of all types are beginning to engage in oral health, both
      academically and in practice. The process has been slow; however, momentum has
      increased over the past two decades as major health care organizations have
      emphasized the importance of oral health as a vital part of overall health. This
      article begins by defining which health providers have and should engage the
      public in oral health and then briefly reviews the influences that have led
      health professionals to address oral health in education and practice. This
      overview is followed by an examination of current trends and successes in oral
      health education in the health sciences, why oral health is a natural fit for
      medical care, and the need for a comprehensive approach. The article concludes by
      exploring roles for each profession and addressing the resources and political
      will that will be required to meet common goals. This article was written as part
      of the project "Advancing Dental Education in the 21st Century."

PMID- 28765470
TI  - The Role of Oral Health Care Professionals in Providing Medical Services.
AB  - Integration of oral health care professionals (OHCPs) into medical care could
      advance efforts to control increasingly prevalent conditions such as
      cardiovascular disease, diabetes mellitus, human immunodeficiency virus
      infection, and hepatitis C infection, each of which is associated with
      significant morbidity and health care costs. Prevention and early intervention
      are effective for reducing the incidence and severity of these diseases, while
      increasing cost of health care may drive the need for nontraditional models of
      health education and delivery. Studies have suggested that a dental office is a
      suitable setting for the purpose of screening and referrals for these conditions
      and may result in medical expenditure savings. Such innovations would challenge
      the current dental educational model and the education and training of faculty.
      Implementing this change would require recognizing opportunities and challenges
      for the profession and the need for new competencies in dental curricula.
      Challenges and opportunities are described, including reimbursement models and
      integration of OHCPs into emerging health care delivery models. Ideas for
      curricular change are presented, including the need for added emphasis on
      biological sciences and the introduction of new courses to address systems
      thinking and forces driving preventive behavior. To embrace the evolving health
      care arena and be a part of the future interprofessional health care delivery
      dynamic, dental curricula should also include substantive interprofessional
      education opportunities. Such opportunities would provide the basic skills and
      training to recognize and appreciate patients' oral health issues in the broader
      context of their overall health and well-being. This article was written as part
      of the project "Advancing Dental Education in the 21st Century."

PMID- 28765471
TI  - The Future of Interprofessional Education and Practice for Dentists and Dental
      Education.
AB  - In the ever-changing landscape of education, health professions programs must be
      adaptable and forward-thinking. Programs need to understand the services students
      should be educated to provide over the next 25 years. The movement to increase
      collaboration among health professionals to improve health care outcomes is a
      significant priority for all health professions. Complex medical issues
      frequently seen in patients can best be addressed with interprofessional health
      care teams. Training future health care providers to work in such teams
      facilitates collaborative care and can result in improved outcomes for patients.
      What skills will dental students need in 2040 to practice as part of these
      interprofessional teams? Important skills needed for success are collaboration,
      communication, professionalism, and the ability to manage medically complex
      patients. These abilities are in alignment with the four Interprofessional
      Education Collaborative (IPEC) core competency domains and will continue to be
      key skills necessary in the future. Transitioning to a one university approach
      for preclinical and clinical training along with development of an all-inclusive
      electronic health record will drive this model forward. Faculty training and
      continuing education for clinicians, residents, and allied health providers will
      be necessary for comprehensive adoption of a team-based collaborative care
      system. With the health care delivery system moving towards more patient
      centered, team-based care, interprofessional education helps future clinicians
      develop into confident team members who will lead health care into the future and
      produce better patient outcomes. This article was written as part of the project
      "Advancing Dental Education in the 21st Century."

PMID- 28765472
TI  - High on drugs: lessons from opiates in pancreatitis.

PMID- 28765473
TI  - Faecal microbiota composition associates with abdominal pain in the general
      population.

PMID- 28765475
TI  - Serrated pathway: a paradigm shift in CRC prevention.

PMID- 28765474
TI  - Mucosal microbiome dysbiosis in gastric carcinogenesis.
AB  - OBJECTIVES: We aimed to characterise the microbial changes associated with
      histological stages of gastric tumourigenesis. DESIGN: We performed 16S rRNA gene
      analysis of gastric mucosal samples from 81 cases including superficial gastritis
      (SG), atrophic gastritis (AG), intestinal metaplasia (IM) and gastric cancer (GC)
      from Xi'an, China, to determine mucosal microbiome dysbiosis across stages of GC.
      We validated the results in mucosal samples of 126 cases from Inner Mongolia,
      China. RESULTS: We observed significant mucosa microbial dysbiosis in IM and GC
      subjects, with significant enrichment of 21 and depletion of 10 bacterial taxa in
      GC compared with SG (q<0.05). Microbial network analysis showed increasing
      correlation strengths among them with disease progression (p<0.001). Five GC
      enriched bacterial taxa whose species identifications correspond to
      Peptostreptococcus stomatis, Streptococcus anginosus, Parvimonas micra, Slackia
      exigua and Dialister pneumosintes had significant centralities in the GC
      ecological network (p<0.05) and classified GC from SG with an area under the
      receiver-operating curve (AUC) of 0.82. Moreover, stronger interactions among
      gastric microbes were observed in Helicobacter pylori-negative samples compared
      with H. pylori-positive samples in SG and IM. The fold changes of selected
      bacteria, and strengths of their interactions were successfully validated in the
      Inner Mongolian cohort, in which the five bacterial markers distinguished GC from
      SG with an AUC of 0.81. CONCLUSIONS: In addition to microbial compositional
      changes, we identified differences in bacterial interactions across stages of
      gastric carcinogenesis. The significant enrichments and network centralities
      suggest potentially important roles of P. stomatis, D. pneumosintes, S. exigua,
      P. micra and S. anginosus in GC progression.

PMID- 28765476
TI  - Annexin A11 is targeted by IgG4 and IgG1 autoantibodies in IgG4-related disease.
AB  - OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan immune
      mediated disease that predominantly affects the biliary tract (IgG4-associated
      cholangitis, IAC) and pancreas (autoimmune pancreatitis, AIP). We recently
      identified highly expanded IgG4+ B-cell receptor clones in blood and affected
      tissues of patients with IAC/AIP suggestive of specific (auto)antigenic stimuli
      involved in initiating and/or maintaining the inflammatory response. This study
      aimed to identify (auto)antigen(s) that are responsible for the clonal expansion
      of IgG4+ B cells in IgG4-RD. DESIGN: We screened sera of patients with IAC/AIP
      (n=50), in comparison to control sera of patients with primary sclerosing
      cholangitis (PSC) and pancreatobiliary malignancies (n=47), for reactivity
      against human H69 cholangiocyte lysates on immunoblot. Subsequently, target
      antigens were immunoprecipitated and analysed by mass spectrometry. RESULTS:
      Prominent reactivity against a 56 kDa protein was detected in human H69
      cholangiocyte lysates exposed to sera of nine patients with IAC/AIP. Affinity
      purification and mass spectrometry analysis identified annexin A11, a calcium
      dependent phospholipid-binding protein. Annexin A11-specific IgG4 and IgG1
      antibodies were only detected in serum of patients with IgG4-RD of the biliary
      tract/pancreas/salivary glands and not in disease mimickers with PSC and
      pancreatobiliary malignancies. Epitope analysis showed that two annexin A11
      epitopes targeted by IgG1 and IgG4 autoantibodies were shared between patients
      with IAC/AIP and IgG4 antibodies blocked binding of IgG1 antibodies to the shared
      annexin A11 epitopes. CONCLUSION: Our data suggest that IgG1-mediated pro
      inflammatory autoreactivity against annexin A11 in patients with IgG4-RD may be
      attenuated by formation of annexin A11-specific IgG4 antibodies supporting an
      anti-inflammatory role of IgG4 in IgG4-RD.

PMID- 28765477
TI  - Triggering of the abductor pollicis longus in association with deQuervain's
      tenosynovitis.
AB  - DeQuervain's tenosynovitis is a common cause of radial-sided wrist pain. Symptoms
      result from a narrow first dorsal compartment and associated tendinosis of the
      enclosed extensor pollicis brevis and/or abductor pollicis longus (APL). Surgical
      intervention, offered when conservative measures fail to adequately relieve
      symptoms, requires a detailed understanding of potentially aberrant anatomy in
      order to avoid persistence or recurrence of symptoms. We describe a case whereby
      the patient presented with complaints of thumb triggering in extension and
      associated disabling first dorsal compartment tendinosis. Intraoperatively, after
      supernumerary tendons were identified and addressed, the APL was at risk for
      subluxation over a prominent fibroosseous ridge. Routine first dorsal compartment
      release alone may have failed to address all of this patient's pathology.

PMID- 28765478
TI  - Valacyclovir-associated neurotoxicity treated with intensification of peritoneal
      dialysis.
AB  - We report a 57-year-old woman with end-stage renal disease (ESRD) on maintenance
      peritoneal dialysis (PD), who presented to the emergency room (ER) by ambulance
      with complaints of confusion and altered sensorium for 48 hours. She had been
      reviewed in a walk-in clinic 72 hours earlier and had been prescribed the
      standard 1000 mg three times per day of valacyclovir for an acute attack of
      shingles instead of 500 mg once a day on ESRD. In the ER, she received further
      500 mg of intravenous acyclovir as herpes encephalitis was clinically suspected.
      CT of the brain and lumbar puncture were non-contributory to the diagnosis.
      Valacyclovir and acyclovir were discontinued when the diagnosis of valacyclovir
      associated neurotoxicity became clinically evident. As the patient's Glasgow Coma
      Scale declined, we intensified her PD regimen from one to six exchanges per day
      and 24 hours later there was a significant neurological improvement.

PMID- 28765479
TI  - Early intracardiac thrombus and pulmonary embolus after trauma.
AB  - Here, we present the case of a patient with the findings of an early intracardiac
      thrombus and a pulmonary embolus after major trauma. A large clot was identified
      extending from the inferior vena cava into the right atrium and ventricle in the
      setting of preserved right ventricular function. Post-traumatic intracardiac
      thrombus is extremely rare and no comparable cases have previously been described
      in the absence of a congenital heart defect and obvious myocardial injury. Best
      practice afterpost-traumatic intracardiac thrombus is not well established but we
      found that early inferior vena cava filter placement and treatment with
      therapeutic coagulation resulted in clinical improvement, resolution of the
      thrombus and no further emboli. The successful use of rivaroxaban, a direct
      acting oral anticoagulant, to treat a right heart thrombus has, to our knowledge,
      not previously been reported. Early acute traumatic coagulopathy has received
      much attention but the hypercoagulable state that often follows is less well
      appreciated.

PMID- 28765480
TI  - Tuberculosis presenting as broncho-oesophageal fistula in a young healthy man.
AB  - A 21-year-old Saudi man presented with a history of dysphagia and choking. CT
      scan of the chest showed clear evidence of chronic recurrent aspiration pneumonia
      in the left lung. It also showed a fistula connecting the left main bronchus to
      the oesophagus. Endoscopy showed clear opening on the oesophageal side.
      Bronchoscopy also confirmed the presence of a broncho-oesophageal fistula on the
      left bronchial side with the presence of secretions on swallowing.
      Bronchoalveolar lavage (BAL) was done and sent for mycobacterial tuberculosis
      culture. The fistula was closed with clips under endoscopic guidance, which
      alleviated his symptoms of dysphagia and choking. The BAL culture grew
      mycobacterial tubercle bacilli. The patient showed marked improvement after
      starting antitubercular therapy and was discharged to be followed up in the
      clinic.

PMID- 28765481
TI  - Carotid dissection presenting as a prolonged cluster-like headache in a patient
      with episodic cluster headache.
AB  - We present a patient with known episodic cluster headache, who presented with
      cluster-like headache in the course of internal carotid artery dissection (ICAD)
      and discuss possible pathophysiological links between the two diseases. It is
      well known that cluster-like headache could be the presenting symptom of ICAD.
      However, ICAD occurring in a patient with a known episodic cluster headache was
      only once previously described. In the end of the manuscript, we propose red
      flags to help clinicians differentiate between primary cluster headache and
      cluster-like attacks masking underlying ICAD. Finally, we raise the question
      whether at least some proportion of those patients with cluster headache and
      Horner syndrome previously classified as a primary headache disorder might have
      been secondary cases to ICAD.

PMID- 28765482
TI  - The non-resolving lung cavity: a case of pulmonary cystic echinococcosis.
AB  - The authors report a case of a 20-year-old woman who was diagnosed with pulmonary
      cystic echinococcosis. She was admitted to hospital with a 1-week history of
      unresolving cough, coloured sputum with occasional haemoptysis and fever despite
      oral antibiotics. Radiology revealed a cavitating right lower lobe lung abscess.
      After 4 weeks of treatment, follow-up radiology showed incomplete resolution.
      Bronchoscopy revealed a white, avascular cystic lesion in the right lower lobe
      and serology testing for Echinococcus granulosus was positive. Repeat imaging
      eventually confirmed the cystic lesion with the 'air bubble'sign. A thorough
      travel history, a high index of clinical suspicion and close follow-up are
      essential in making a diagnosis of pulmonary cystic echinococcosis.

PMID- 28765483
TI  - Acquired capillary haemangioma of the eyelid in a 10-year-old boy.
AB  - A 10-year-old boy presented with painless, gradually increasing mass in right
      upper lid without preceding trauma for the past 2 months. On examination, the
      mass was bluish red, soft to firm in consistency which bleeds on touch. Contrast
      enhanced CT showed a well-defined heterogeneously enhancing mass lesion without
      any continuity with the underlying bone or the orbital cavity. Complete excision
      of the mass was performed under general anaesthesia, subsequent histopathological
      examination showed findings consistent with an acquired variant of capillary
      haemangioma. At the end of 1 year, patient is cosmetically fine without any
      recurrence/morbidity.

PMID- 28765484
TI  - Double whammy: a tale of two malignancies.

PMID- 28765485
TI  - Large chordoma of the sacrum.

PMID- 28765486
TI  - Peripheral hepatojejunostomy: a last resort palliative solution in Greece during
      the economic crisis.
AB  - The geographical distribution of Greece and the growing proportion of uninsured
      patients make imperative the need for effective and efficient palliative
      solutions regarding obstructive jaundice due to hepatic malignancy, while
      repeated endoscopic interventions and all associated materials are either not
      accessible to the whole population or not even available on a daily basis due to
      the economic crisis and the difficulties on the hospital supply. On this basis,
      palliative hepatojejunostomy, introduced more than 50 years ago, could be
      revisited in the Greek reality in very selected cases and under these special
      circumstances. We report on two patients with locally advanced hilar
      cholangiocarcinoma and intrahepatic cholangiocarcinoma, respectively, who were
      treated with a combination of double hepaticojejunostomy with peripheral
      hepatojejunostomy or peripheral hepatoejunostomy alone, respectively. Both
      patients experienced an adequate decompression of the biliary tract over more
      than a year. Palliative hepatojejunostomy could be an ultimate solution for
      selected patients and circumstances in Greece during the economic crisis.

PMID- 28765487
TI  - Huge cardiac myxoma in pregnancy.
AB  - A 28-year-old pregnant woman presented at 28 weeks of gestation. She was
      diagnosed to have a left atrial myxoma 2 years earlier, but was lost to follow
      up. During this pregnancy, the transthoracic echocardiography showed a 9 cm mass
      in the left atrium obstructing mitral valve inflow, interfering with mitral valve
      closure, causing severe mitral regurgitation and severe pulmonary hypertension.
      However, there were no clinical signs of pulmonary and systemic congestion or
      obstruction. Based on the clinical symptoms of the patient, the echocardiographic
      findings and the term of her pregnancy, the patient decided to schedule for a
      vaginal delivery with surgical correction after delivery. She gave birth at 32
      weeks of gestation. During labour, pulmonary oedema developed but was detected
      early and it responded to therapy. Two weeks after delivery, a right anterior
      thoracotomy was performed to facilitate the removal of the left atrial myxoma and
      repair of the mitral valve.

PMID- 28765488
TI  - Wernickea?TMs encephalopathy associated with liver abscess.
AB  - Wernicke's encephalopathy is a rare neurological disorder caused by thiamine
      deficiency, characterised by ocular motor dysfunction, ataxia and impairment in
      consciousness. It predominantly affects brain regions with a high metabolic rate
      such as mammillary bodies, medial thalamic nuclei, the tectal region and the
      cerebellum. Although chronic alcoholism is the most common cause of Wernicke's
      encephalopathy, various other conditions not related to alcohol consumption such
      as bariatric surgery, acute pancreatitis, hyperemesis gravidarum, prolonged
      fasting and gastrointestinal surgery have been implicated in its aetiology. We
      report the case of a patient who underwent surgery for liver abscess and
      subsequently developed Wernicke's encephalopathy; he showed a positive response
      to thiamine supplementation. This is the first report describing liver abscess as
      the cause of Wernicke's encephalopathy.

PMID- 28765489
TI  - Embryonal carcinoma presenting as a calcified solitary testicular mass on
      ultrasound.
AB  - A 24-year-old man presented with a 2-week history of a painless right testicular
      mass; ultrasound demonstrated a dense, solitary calcified mass. The patient
      elected observation after further workup showed no evidence of metastasis.A
      repeat ultrasound 3 months later showed interval growth and the patient underwent
      right radical orchiectomy. Pathology was consistent with pure embryonal carcinoma
      of the testis. Calcified testicular masses are typically benign but do carry a
      differential of spermatic granuloma, large-cell calcifying Sertoli cell tumour,
      trauma, tuberculosis, filariasis, calcified Leydig cell tumour and burned-out
      testicular tumour.To our knowledge, this is the first case report of pure
      embryonal carcinoma presenting as a solitary calcified testicular mass.

PMID- 28765490
TI  - Incidental finding of persistent left superior vena cava after 'bubble study'
      verification of central venous catheter.
AB  - We report a case of a patient with septic shock who underwent central venous
      catheter placement in the left internal jugular vein, and a bedside ultrasound
      'bubble study' revealed venous cannulation. A chest X-ray postprocedure revealed
      concern for arterial system catheterisation. However, the possibility of a
      persistent left superior vena cava was discussed and confirmed with a formal
      transthoracic echocardiogram and CT. This case demonstrates the importance of
      ultrasound-guided visualisation of anatomical structures in real time during
      central venous catheterisation. Other similar cases from the literature are
      briefly described.

PMID- 28765491
TI  - Turbulent tackle: a novel surgical approach to a rugby-related jejunal
      perforation.
AB  - Viscus perforation in the context of blunt-force abdominal trauma is a rarity.
      Within a sporting context, it is especially rare. However, the increasing
      physicality observed in rugby union, both in the amateur and professional
      setting, has resulted in a higher rate of serious injury. We report a novel
      laparoscopic surgical approach to the management of a traumatic jejunal
      perforation sustained on the playing field in a previously fit and healthy 28
      year-old.

PMID- 28765492
TI  - Pseudo retinitis pigmentosa in a case of missed intraocular foreign body.
AB  - A 35-year-old man presented with history of painless, progressive loss of vision
      in the left eye for the past 7 years. There was history of trauma to the same eye
      with an iron object 7 years prior. Fundus examination revealed pigmentary
      retinopathy (unilateral advanced retinitis pigmentosa (RP)-like picture). X-ray
      orbits were suspicious of retained intraocular foreign body (IOFB). CT orbits
      confirmed the presence of IOFB. Electroretinogram revealed depressed responses.
      Right eye examination was within normal limits. A diagnosis of siderosis bulbi
      with unilateral pseudo RP-like fundus was made. No surgical intervention was
      planned for IOFB in view of poor visual prognosis.

PMID- 28765493
TI  - Variability of Tidal Volume in Patient-Triggered Mechanical Ventilation in ARDS.
AB  - BACKGROUND: Limiting tidal volume (VT) in patients with ARDS may not be achieved
      once patient-triggered breaths occur. Furthermore, ICU ventilators offer numerous
      patient-triggered modes that work differently across brands. We systematically
      investigated, using a bench model, the effect of patient-triggered modes on the
      size and variability of VT at different breathing frequencies (f), patient
      effort, and ARDS severity. METHODS: We used a V500 Infinity ICU ventilator
      connected to an ASL 5000 lung model whose compliance was mimicking mild,
      moderate, and severe ARDS. Thirteen patient-triggered modes were tested, falling
      into 3 categories, namely volume control ventilation with mandatory minute
      ventilation; pressure control ventilation, including airway pressure release
      ventilation (APRV); and pressure support ventilation. Two levels of f and effort
      were tested for each ARDS severity in each mode. Median (first-third quartiles)
      VT was compared across modes using non-parametric tests. The probability of VT >
      6 mL/kg ideal body weight was assessed by binomial regression and expressed as
      the odds ratio (OR) with 95% CI. VT variability was measured from the coefficient
      of variation. RESULTS: VT distribution over all f, effort, and ARDS categories
      significantly differed across modes (P < .001, Kruskal-Wallis test). VT was
      significantly greater with pressure support (OR 420 mL, 95% CI 332-527 mL) than
      with any other mode except for variable pressure support level. Risk for VT to be
      > 6 mL/kg was significantly increased with spontaneous breaths patient-triggered
      by pressure support (OR 19.36, 95% CI 12.37-30.65) and significantly reduced in
      APRV (OR 0.44, 95% CI 0.26-0.72) and pressure support with guaranteed volume
      mode. The risk increased with increasing effort and decreasing f. Coefficient of
      variation of VT was greater for low f and volume control-mandatory minute
      ventilation and pressure control modes. APRV had the greatest within-mode
      variability. CONCLUSIONS: Risk of VT > 6 mL/kg was significantly reduced in APRV
      and pressure support with guaranteed volume mode. APRV had the highest
      variability. Pressure support with guaranteed volume could be tested in patients
      with ARDS.

PMID- 28765494
TI  - Effects of Expiratory Positive Airway Pressure on Exercise Tolerance, Dynamic
      Hyperinflation, and Dyspnea in COPD.
AB  - INTRODUCTION: The application of expiratory positive airway pressure (EPAP) in
      patients with COPD during exercise may reduce dynamic hyperinflation, while, on
      the other hand, it can increase the resistive work of breathing. Therefore, we
      evaluated the effects of 2 intensities of EPAP during exercise on tolerance,
      dynamic hyperinflation, and dyspnea in subjects with moderate to very severe
      COPD. METHODS: We performed a cross-sectional, experimental, 4-visit study. In
      visit 1, subjects performed symptom-limited cycling incremental cardiopulmonary
      exercise test (CPET). In visits 2-4, at least 48 h apart, in a randomized order,
      subjects performed constant CPET without EPAP, EPAP with 5 cm H2O (EPAP5), or
      EPAP with 10 cm H2O (EPAP10). RESULTS: The study included 15 non-hypoxemic
      subjects ranging from moderate to very severe COPD (mean FEV1 = 35 +/- 11%
      predicted). Increasing intensities of EPAP during constant CPET tended to cause
      progressive reduction in exercise tolerance (P = .11). Of note, 10 of 15 subjects
      demonstrated significantly shorter average exercise duration with EPAP10 compared
      to the test without EPAP (-151 +/- 105 s, P = .03 or -41 +/- 26%). Minute
      ventilation increment was constrained by EPAP, secondary to a limited increase in
      tidal volume (P = .01). Finally, dyspnea sensation and serial measurements of
      inspiratory capacity during exercise were similar when comparing the three
      interventions at isotime and at end-constant CPETs. CONCLUSIONS: The application
      of EPAP5 or EPAP10 during exercise tended to cause a progressive reduction in
      exercise tolerance in subjects with COPD without improvement in dyspnea or
      dynamic hyperinflation at equivalent exercise duration.

PMID- 28765495
TI  - Validating Reference Equations for Impulse Oscillometry in Healthy Mexican
      Children.
AB  - BACKGROUND: The impulse oscillometry system (IOS) measures the impedance (Z) of
      the respiratory system, but proper interpretation of its results requires
      adequate reference values. The objectives of this work were: (1) to validate the
      reference equations for the IOS published previously by our group and (2) to
      compare the adjustment of new available reference equations for the IOS from
      different countries in a sample of healthy children. METHODS: Subjects were
      healthy 4-15-y-old children from the metropolitan area of Mexico City, who
      performed an IOS test. The functional IOS parameters obtained were compared with
      the predicted values from 12 reference equations determined in studies of
      different ethnic groups. The validation methods applied were: analysis of the
      differences between measured and predicted values for each reference equation;
      correlation and concordance coefficients; adjustment by Z-score values;
      percentage of predicted value; and the percentage of patients below the lower
      limit of normality or above the upper limit of normality. RESULTS: Of the 224
      participants, 117 (52.3%) were girls, and the mean age was 8.6 +/- 2.3 y. The
      equations that showed the best adjustment for the different parameters were those
      from the studies by Nowowiejska et al (2008) and Gochicoa et al (2015). The
      equations proposed by Frei et al (2005), Hellinckx et al (1998), Kalhoff et al
      (2011), Klug and Bisgaard (1998), de Assumpcao et al (2016), and Dencker et al
      (2006) overestimated the airway resistance of the children in our sample, whereas
      the equation of Amra et al (2008) underestimated it. In the analysis of the lower
      and upper limits of normality, Gochicoa et al equation was the closest, since 5%
      of subjects were below or above percentiles 5 and 95, respectively. The study
      found that, in general, all of the equations showed greater error at the extremes
      of the age distribution. CONCLUSIONS: Because of the robust adjustment of the
      present study reference equations for the IOS, it can be recommended for both
      clinical and research purposes in our population. The differential adjustment of
      other equations underlines the need to obtain local reference values.

PMID- 28765496
TI  - Impact of a Post-Discharge Integrated Disease Management Program on COPD Hospital
      Readmissions.
AB  - BACKGROUND: Readmission following a hospitalization for COPD is associated with
      significant health-care expenditure. METHODS: A multicomponent COPD post
      discharge integrated disease management program was implemented at the Cleveland
      Clinic to improve the care of patients with COPD and reduce readmissions. This
      retrospective study reports our experience with the program. Groups of subjects
      who were exposed to different components of the program were compared regarding
      their readmission rates. Multivariate logistic regression analysis was performed
      to build predictive models for 30- and 90-d readmission. RESULTS: One hundred
      sixty subjects completed a 90-d follow-up, of which, 67 attended the exacerbation
      clinic, 16 subjects received care coordination, 51 subjects completed both, and
      26 subjects did not participate in any component despite referral. Thirty- and 90
      d readmission rates for the entire group were 18.1 and 46.2%, respectively.
      Thirty- and 90-d readmission rates for the individual groups were: exacerbation
      clinic, 11.9 and 35.8%; care coordination, 25.0 and 50.0%; both, 19.6 and 41.2%;
      and neither, 26.9 and 80.8%, respectively. The model with the best predictive
      ability for 30-d readmission risk included the number of hospitalizations within
      the previous year and use of noninvasive ventilation (C statistic of 0.84). The
      model for 90-d readmission risk included receiving any component of the post
      discharge integrated disease management program, the number of hospitalizations,
      and primary care physician visits within the previous year (C statistic of 0.87).
      CONCLUSIONS: Receiving any component of a post-discharge integrated disease
      management program was associated with reduced 90-d readmission rate. Previous
      health-care utilization and lung function impairment were strong predictors of
      readmission.

PMID- 28765497
TI  - Isolation of Brachyspira species from farmed wild boar in Spain.

PMID- 28765498
TI  - Are serum amyloid A or D-lactate useful to diagnose synovial contamination or
      sepsis in horses?
AB  - Synovial sepsis in horses is life threatening and accurate diagnosis allowing
      prompt treatment is warranted. This study assessed the diagnostic value of serum
      amyloid A (SAA) and D-lactate in blood and synovial fluid (SF) as diagnostic
      markers of synovial sepsis in horses and correlated them with total nucleated
      cell count (TNCC), percentage of neutrophils (%N) and total protein (TP) in SF.
      Blood and SF SAA and D-lactate concentrations were determined in a case-control
      observational study including 112 horses (38 with synovial contamination or
      sepsis (SCS), 66 with non-septic intra-synovial pathology (NSISP) and 8
      controls). Blood and SF SAA were significantly higher in SCS than in NSISP and
      control horses. SAA values were similar in NSISP and control horses. SF SAA was
      moderately correlated with synovial TNCC, TP and blood SAA. Blood and SF SAA were
      82.4 per cent and 80 per cent sensitive and 88.9 per cent and 73 per cent
      specific for diagnosis of SCS, with cut-off values of 60.7 and 1.14 ug/ml,
      respectively. Blood and SF D-lactate concentrations were not significantly
      different between groups. This study shows that blood and SF SAA concentrations
      can aid to distinguish SCS from non-septic synovial pathology; however, D-lactate
      was not useful.

PMID- 28765499
TI  - Real-time PCR for the detection of Leptospira species in lungworm preparations.

PMID- 28765501
TI  - Comparison of flocked and rayon swabs for the molecular detection of selected
      equine viruses and bacteria from nasal secretions of healthy horses.

PMID- 28765500
TI  - Infectious keratoconjunctivitis and occurrence of Mycoplasma conjunctivae and
      Chlamydiaceae in small domestic ruminants from Central Karakoram, Pakistan.
AB  - Infectious keratoconjunctivitis (IKC) is a contagious eye disease primarily
      caused by Mycoplasma conjunctivae in domestic and wild Caprinae. Chlamydophila
      species have also been detected in ruminants with IKC. The objectives of this
      study are to investigate the ocular infection of M. conjunctivae and
      Chlamydiaceae and assess its interaction in relation to IKC in sheep and goats
      from remote communities around the Central Karakoram National Park in Pakistan,
      performing a combination of cross-sectional and case-control study design. Mostly
      asymptomatic and endemic infections of M. conjunctivae and Chlamydiaceae were
      found in sheep (19.3 per cent and 4.5 per cent, respectively) and goats (9.5 per
      cent and 1.9 per cent, respectively) from all communities, assessed by qPCR.
      Prevalence significantly differed between species only for M. conjunctivae
      (P=0.0184), which was also more prevalent in younger sheep (P<0.01).
      Chlamydophila pecorum was identified by sequencing and was related with IKC only
      when coinfection with M. conjunctivae occurred, which suggest a synergic
      interaction. Cluster analysis of M. conjunctivae strains revealed higher
      diversity of strains than expected, evidenced interspecific transmission and
      suggested a higher local livestock trade than previously assumed. These results
      highlight the widespread occurrence of M conjunctivae in sheep worldwide and its
      implications for wildlife should be assessed from a conservation perspective.

PMID- 28765502
TI  - A Phase II Study with Lead-In Safety Cohort of 5-Fluorouracil, Oxaliplatin, and
      Lapatinib in Combination with Radiation Therapy as Neoadjuvant Treatment for
      Patients with Localized HER2-Positive Esophagogastric Adenocarcinomas.
AB  - LESSONS LEARNED: Neoadjuvant 5-fluorouracil, oxaliplatin, and lapatinib in
      combination with radiation therapy is safe for neoadjuvant treatment for patients
      with localized human epidermal growth receptor 2-positive esophagogastric
      adenocarcinoma.Evaluation of this drug combination in a larger patient pool would
      allow for more accurate analysis of its efficacy. BACKGROUND: The optimal design
      of neoadjuvant chemoradiation for the treatment of localized esophagogastric
      cancers is the subject of much debate. In this nonrandomized trial, we evaluated
      neoadjuvant 5-fluorouracil (5-FU), oxaliplatin, and lapatinib in combination with
      radiation therapy as neoadjuvant treatment for patients with localized human
      epidermal growth receptor 2 (HER2)-positive esophagogastric adenocarcinomas.
      METHODS: Patients received neoadjuvant 5-FU (225 mg/m2 continuous intravenous
      infusion, days 1-42), oxaliplatin (85 mg/m2 intravenously [IV], days 1, 15, and
      29), and lapatinib (six patients, 1,000 mg p.o., days 1-42; six patients, 750 mg
      p.o., days 1-42) plus radiation (1.8 Gy/day Monday through Friday for 50.4 Gy
      total). Following restaging, eligible patients underwent definitive resection,
      and pathologic response to neoadjuvant therapy was assessed. Planned enrollment
      was 42 patients. The primary endpoint was the pathologic complete response (pCR)
      rate. RESULTS: Twelve patients (median age 64 years; 67% male) received a median
      of 5.6 weeks of treatment (range: 1.1-8.4). The pCR rate was 8%; four of the 12
      patients underwent tumor resection and one patient had a pCR, with pathologic
      partial response in the remaining three. The most common lapatinib-related
      adverse events included (all grades) nausea (67%) and diarrhea (58%), although
      these were all grade 1 or 2. Enrollment was halted due to low accrual.
      CONCLUSION: The treatment regimen was determined to be safe. The study was
      terminated early due to low accrual.

PMID- 28765504
TI  - Does early return to theatre add value to rates of revision at 3 years in
      assessing surgeon performance for elective hip and knee arthroplasty? National
      observational study.
AB  - BACKGROUND: Joint replacement revision is the most widely used long-term outcome
      measure in elective hip and knee surgery. Return to theatre (RTT) has been
      proposed as an additional outcome measure, but how it compares with revision in
      its statistical performance is unknown. METHODS: National hospital administrative
      data for England were used to compare RTT at 90 days (RTT90) with revision rates
      within 3 years by surgeon. Standard power calculations were run for different
      scenarios. Funnel plots were used to count the number of surgeons with unusually
      high or low rates. RESULTS: From 2006 to 2011, there were 297 650 hip
      replacements (HRs) among 2952 surgeons and 341 226 knee replacements (KRs) among
      2343 surgeons. RTT90 rates were 2.1% for HR and 1.5% for KR; 3-year revision
      rates were 2.1% for HR and 2.2% for KR. Statistical power to detect surgeons with
      poor performance on either metric was particularly low for surgeons performing 50
      cases per year for the 5 years. The correlation between the risk-adjusted surgeon
      level rates for the two outcomes was +0.51 for HR and +0.20 for KR, both p<0.001.
      There was little agreement between the measures regarding which surgeons had
      significantly high or low rates. CONCLUSION: RTT90 appears to provide useful and
      complementary information on surgeon performance and should be considered
      alongside revision rates, but low case loads considerably reduce the power to
      detect unusual performance on either metric.

PMID- 28765503
TI  - Advance Directives, Hospitalization, and Survival Among Advanced Cancer Patients
      with Delirium Presenting to the Emergency Department: A Prospective Study.
AB  - BACKGROUND: To improve the management of advanced cancer patients with delirium
      in an emergency department (ED) setting, we compared outcomes between patients
      with delirium positively diagnosed by both the Confusion Assessment Method (CAM)
      and Memorial Delirium Assessment Scale (MDAS), or group A (n = 22); by the MDAS
      only, or group B (n = 22); and by neither CAM nor MDAS, or group C (n = 199).
      MATERIALS AND METHODS: In an oncologic ED, we assessed 243 randomly selected
      advanced cancer patients for delirium using the CAM and the MDAS and for presence
      of advance directives. Outcomes extracted from patients' medical records included
      hospital and intensive care unit admission rate and overall survival (OS).
      RESULTS: Hospitalization rates were 82%, 77%, and 49% for groups A, B, and C,
      respectively (p = .0013). Intensive care unit rates were 18%, 14%, and 2% for
      groups A, B, and C, respectively (p = .0004). Percentages with advance directives
      were 52%, 27%, and 43% for groups A, B, and C, respectively (p = .2247). Median
      OS was 1.23 months (95% confidence interval [CI] 0.46-3.55) for group A, 4.70
      months (95% CI 0.89-7.85) for group B, and 10.45 months (95% CI 7.46-14.82) for
      group C. Overall survival did not differ significantly between groups A and B (p
      = .6392), but OS in group C exceeded those of the other groups (p < .0001 each).
      CONCLUSION: Delirium assessed by either CAM or MDAS was associated with worse
      survival and more hospitalization in patients with advanced cancer in an
      oncologic ED. Many advanced cancer patients with delirium in ED lack advance
      directives. Delirium should be assessed regularly and should trigger discussion
      of goals of care and advance directives. IMPLICATIONS FOR PRACTICE: Delirium is a
      devastating condition among advanced cancer patients. Early diagnosis in the
      emergency department (ED) should improve management of this life-threatening
      condition. However, delirium is frequently missed by ED clinicians, and the
      outcome of patients with delirium is unknown. This study finds that delirium
      assessed by the Confusion Assessment Method or the Memorial Delirium Assessment
      Scale is associated with poor survival and more hospitalization among advanced
      cancer patients visiting the ED of a major cancer center, many of whom lack
      advance directives. Therefore, delirium in ED patients with cancer should trigger
      discussion about advance directives.

PMID- 28765505
TI  - Drug shortage leading to serendipitous adoption of high-value care practice.

PMID- 28765506
TI  - Opinion: Finding the plot in science storytelling in hopes of enhancing science
      communication.

PMID- 28765508
TI  - Editorial: Myeloid-derived suppressor cells: a new therapeutic target in sepsis
      patients.

PMID- 28765509
TI  - Editorial: Teaching old CAR-T cells new tricks.

PMID- 28765510
TI  - The Arabidopsis LAZY1 Family Plays a Key Role in Gravity Signaling within
      Statocytes and in Branch Angle Control of Roots and Shoots.
AB  - During gravitropism, the directional signal of gravity is perceived by gravity
      sensing cells called statocytes, leading to asymmetric distribution of auxin in
      the responding organs. To identify the genes involved in gravity signaling in
      statocytes, we performed transcriptome analyses of statocyte-deficient
      Arabidopsis thaliana mutants and found two candidates from the LAZY1 family,
      AtLAZY1/LAZY1-LIKE1 (LZY1) and AtDRO3/AtNGR1/LZY2 We showed that LZY1, LZY2, and
      a paralog AtDRO1/AtNGR2/LZY3 are redundantly involved in gravitropism of the
      inflorescence stem, hypocotyl, and root. Mutations of LZY genes affected early
      processes in gravity signal transduction without affecting amyloplast
      sedimentation. Statocyte-specific expression of LZY genes rescued the mutant
      phenotype, suggesting that LZY genes mediate gravity signaling in statocytes
      downstream of amyloplast displacement, leading to the generation of asymmetric
      auxin distribution in gravity-responding organs. We also found that lzy mutations
      reversed the growth angle of lateral branches and roots. Moreover, expression of
      the conserved C-terminal region of LZY proteins also reversed the growth
      direction of primary roots in the lzy mutant background. In lateral root tips of
      lzy multiple mutants, asymmetric distribution of PIN3 and auxin response were
      reversed, suggesting that LZY genes regulate the direction of polar auxin
      transport in response to gravity through the control of asymmetric PIN3
      expression in the root cap columella.

PMID- 28765511
TI  - Nitrate Reductase Knockout Uncouples Nitrate Transport from Nitrate Assimilation
      and Drives Repartitioning of Carbon Flux in a Model Pennate Diatom.
AB  - The ecological prominence of diatoms in the ocean environment largely results
      from their superior competitive ability for dissolved nitrate (NO3-). To
      investigate the cellular and genetic basis of diatom NO3- assimilation, we
      generated a knockout in the nitrate reductase gene (NR-KO) of the model pennate
      diatom Phaeodactylum tricornutum In NR-KO cells, N-assimilation was abolished
      although NO3- transport remained intact. Unassimilated NO3- accumulated in NR-KO
      cells, resulting in swelling and associated changes in biochemical composition
      and physiology. Elevated expression of genes encoding putative vacuolar NO3-
      chloride channel transporters plus electron micrographs indicating enlarged
      vacuoles suggested vacuolar storage of NO3- Triacylglycerol concentrations in the
      NR-KO cells increased immediately following the addition of NO3-, and these
      increases coincided with elevated gene expression of key triacylglycerol
      biosynthesis components. Simultaneously, induction of transcripts encoding
      proteins involved in thylakoid membrane lipid recycling suggested more abrupt
      repartitioning of carbon resources in NR-KO cells compared with the wild type.
      Conversely, ribosomal structure and photosystem genes were immediately
      deactivated in NR-KO cells following NO3- addition, followed within hours by
      deactivation of genes encoding enzymes for chlorophyll biosynthesis and carbon
      fixation and metabolism. N-assimilation pathway genes respond uniquely,
      apparently induced simultaneously by both NO3- replete and deplete conditions.

PMID- 28765512
TI  - A cluster of immunoresolvents links coagulation to innate host defense in human
      blood.
AB  - Blood coagulation is a protective response that prevents excessive bleeding upon
      blood vessel injury. We investigated the relationship between coagulation and the
      resolution of inflammation and infection by lipid mediators (LMs) through
      metabololipidomics-based profiling of human whole blood (WB) during coagulation.
      We identified temporal clusters of endogenously produced prothrombotic and
      proinflammatory LMs (eicosanoids), as well as specialized proresolving mediators
      (SPMs). In addition to eicosanoids, a specific SPM cluster was identified that
      consisted of resolvin E1 (RvE1), RvD1, RvD5, lipoxin B4, and maresin 1, each of
      which was present at bioactive concentrations (0.1 to 1 nM). Removal of adenosine
      from the coagulating blood markedly enhanced the amounts of SPMs produced and
      further increased the biosynthesis of RvD3, RvD4, and RvD6. The cyclooxygenase
      inhibitors celecoxib and indomethacin, which block the production of thromboxanes
      and prostanoids, did not block the production of clot-driven SPMs. Unbiased mass
      cytometry analysis demonstrated that the SPM cluster produced in human blood
      targeted leukocytes at the single-cell level, directly activating ERK and CREB
      signaling in neutrophils and CD14+ monocytes. Treatment of human WB with the
      components of this SPM cluster enhanced both the phagocytosis and killing of
      Escherichia coli by leukocytes. Together, these data identify a proresolving LM
      circuit, including endogenous molecular brakes and accelerators, which promoted
      host defense. These temporal LM-SPM clusters can provide accessible metabolomic
      profiles for precision and personalized medicine.

PMID- 28765513
TI  - High glucose-induced ROS activates TRPM2 to trigger lysosomal membrane
      permeabilization and Zn2+-mediated mitochondrial fission.
AB  - Diabetic stress increases the production of reactive oxygen species (ROS),
      leading to mitochondrial fragmentation and dysfunction. We hypothesized that ROS
      sensitive TRPM2 channels mediated diabetic stress-induced mitochondrial
      fragmentation. We found that chemical inhibitors, RNAi silencing, and genetic
      knockout of TRPM2 channels abolished the ability of high glucose to cause
      mitochondrial fission in endothelial cells, a cell type that is particularly
      vulnerable to diabetic stress. Similar to high glucose, increasing ROS in
      endothelial cells by applying H2O2 induced mitochondrial fission. Ca2+ that
      entered through TRPM2 induced lysosomal membrane permeabilization, which led to
      the release of lysosomal Zn2+ and a subsequent increase in mitochondrial Zn2+
      Zn2+ promoted the recruitment of the fission factor Drp-1 to mitochondria to
      trigger their fission. This signaling pathway may operate in aging-associated
      illnesses in which excessive mitochondrial fragmentation plays a central role.

PMID- 28765519
TI  - Effect of Naringin on Monosodium Iodoacetate-Induced Osteoarthritis Pain in Rats.
AB  - BACKGROUND The aim of the current study was to evaluate the anti-osteoarthritic
      and anti-inflammatory effect of naringin in a monosodium iodoacetate (MIA)-
      induced osteoarthritis (OA) model in rats. The anti-osteoarthritic potential of
      naringin was evaluated against the MIA-induced OA rat model. MATERIAL AND METHODS
      Wistar rats were used for the study and were divided into the following groups:
      normal control (saline-treated); group II (MIA-treated): group III
      (MIA+Naringin), and group IV (MIA+Indomethacin). The potential effect of naringin
      was evaluated via its effect on the level of proinflammatory cytokines, measuring
      the weight-bearing distribution, and histopathological analysis. RESULTS The anti
      inflammatory effect of naringin was assessed in vitro in lipopolysaccharide
      induced RAW 264.6 cells. The results suggest that naringin exerts an anti
      inflammatory effect via reducing the production of the prostaglandin E2 (PGE2),
      nitric oxide (NO), interlukin-6 (IL-6), and tumor necrosis factor-alpha (TNF
      alpha) in LPS-induced RAW cells. Additionally, naringin also supported the
      recovery of hind-limb weight-bearing, reduced the generation or production of
      inflammatory mediator and proinflammatory cytokines, and protected the tissue
      from the damage in the OA model. CONCLUSIONS Naringin appears to be an effective
      therapeutic drug for the treatment of the OA and OA-related symptoms.

PMID- 28765521
TI  - Contrast-Enhanced Ultrasound Imaging Quantification of Adventitial Vasa Vasorum
      in a Rabbit Model of Varying Degrees of Atherosclerosis.
AB  - This study used an atherosclerotic rabbit model to investigate the feasibility of
      quantifying adventitial vasa vasorum (VV) via contrast-enhanced ultrasound (CEUS)
      imaging to identify early atherosclerosis. Recent evidence has linked adventitial
      VV with atherosclerotic plaque progression and vulnerability. A growth in VV
      density has been detected preceding intimal thickening and even endothelial
      dysfunction. In our study, carotid atherosclerosis rabbit models were used, and
      animals underwent CEUS imaging at the end of the atherosclerotic induction
      period. Normalized maximal video-intensity enhancement (MVE) was calculated to
      quantify VV density. After CEUS imaging, animals were euthanized, and their
      carotids were processed for histopathological analysis following staining for
      CD31 and VEGF. Adventitial normalized MVE increased as atherosclerosis progressed
      (p < 0.001), and normalized MVE also progressed, demonstrating a linear
      correlation with histological findings (r = 0.634, p < 0.001 for VEGF-positive; r
      = 0.538, p < 0.001 for CD31-positive). Thus, we histologically validated that
      CEUS imaging can be used to quantify the development of adventitial VV associated
      with atherosclerosis progression. This method can be used for monitoring the VV
      to detect early atherosclerosis.

PMID- 28765520
TI  - Semaphorin 4C Plexin-B2 signaling in peripheral sensory neurons is pronociceptive
      in a model of inflammatory pain.
AB  - Semaphorins and their transmembrane receptors, Plexins, are key regulators of
      axon guidance and development of neuronal connectivity. B-type Plexins respond to
      Class IV semaphorins and mediate a variety of developmental functions. Here we
      report that the expression of Plexin-B2 and its high-affinity ligand, Sema4C,
      persists in peripheral sensory neurons in adult life and is markedly increased in
      states of persistent pain in mice. Genetic deletion of Sema4C as well as adult
      onset loss of Plexin-B2 leads to impairment of the development and duration of
      inflammatory hypersensitivity. Remarkably, unlike the neurodevelopmental
      functions of Plexin-B2 that solely rely on Ras signaling, we obtained genetic and
      pharmacological evidence for a requirement of RhoA-ROCK-dependent mechanisms as
      well as TRPA1 sensitization in pronociceptive functions of Sema4C-Plexin-B2
      signaling in adult life. These results suggest important roles for Plexin-B2
      signaling in sensory function that may be of therapeutic relevance in
      pathological pain.Semaphorins and their receptors are involved in
      neurodevelopment, but their functions in the adult nervous system are not fully
      understood. This study finds that semaphorin 4C and its receptor Plexin B are
      expressed in sensory neurons and are pronociceptive in a mouse model of
      inflammatory pain.

PMID- 28765522
TI  - Network Inference and Maximum Entropy Estimation on Information Diagrams.
AB  - Maximum entropy estimation is of broad interest for inferring properties of
      systems across many disciplines. Using a recently introduced technique for
      estimating the maximum entropy of a set of random discrete variables when
      conditioning on bivariate mutual informations and univariate entropies, we show
      how this can be used to estimate the direct network connectivity between
      interacting units from observed activity. As a generic example, we consider phase
      oscillators and show that our approach is typically superior to simply using the
      mutual information. In addition, we propose a nonparametric formulation of
      connected informations, used to test the explanatory power of a network
      description in general. We give an illustrative example showing how this agrees
      with the existing parametric formulation, and demonstrate its applicability and
      advantages for resting-state human brain networks, for which we also discuss its
      direct effective connectivity. Finally, we generalize to continuous random
      variables and vastly expand the types of information-theoretic quantities one can
      condition on. This allows us to establish significant advantages of this approach
      over existing ones. Not only does our method perform favorably in the
      undersampled regime, where existing methods fail, but it also can be dramatically
      less computationally expensive as the cardinality of the variables increases.

PMID- 28765523
TI  - Robust spin correlations at high magnetic fields in the harmonic honeycomb
      iridates.
AB  - The complex antiferromagnetic orders observed in the honeycomb iridates are a
      double-edged sword in the search for a quantum spin-liquid: both attesting that
      the magnetic interactions provide many of the necessary ingredients, while
      simultaneously impeding access. Focus has naturally been drawn to the unusual
      magnetic orders that hint at the underlying spin correlations. However, the study
      of any particular broken symmetry state generally provides little clue about the
      possibility of other nearby ground states. Here we use magnetic fields
      approaching 100 Tesla to reveal the extent of the spin correlations in gamma
      lithium iridate. We find that a small component of field along the magnetic easy
      axis melts long-range order, revealing a bistable, strongly correlated spin
      state. Far from the usual destruction of antiferromagnetism via spin
      polarization, the high-field state possesses only a small fraction of the total
      iridium moment, without evidence for long-range order up to the highest
      attainable magnetic fields.The complex antiferromagnetic orders observed in the
      honeycomb iridates prevent access to a spin-liquid ground state. Here the authors
      apply extremely high magnetic fields to destroy the antiferromagnetic order in
      gamma-lithium iridate and reveal a bistable, strongly correlated spin state.

PMID- 28765524
TI  - Bmal1 regulates inflammatory responses in macrophages by modulating enhancer RNA
      transcription.
AB  - Bmal1 (encoded by Arntl gene) is a core circadian clock gene that regulates
      various genes involved in circadian rhythm. Although Bmal1 is expressed
      rhythmically in macrophages, the role of Bmal1 in the regulation of their
      cellular function remains insufficiently understood. Here, we report that Bmal1
      regulates time-dependent inflammatory responses following Toll-like receptor 4
      (TLR4) activation by modulating enhancer activity. Global transcriptome analysis
      indicated that deletion of Arntl perturbed the time-dependent inflammatory
      responses elicited by TLR4 activation by Kdo2-lipid A (KLA). Although the
      recruitment of NF-kappaB p65 was unaffected, the acetylation status of lysine 27
      of histone 3, which correlates positively with enhancer activity, was globally
      increased at PU.1-containing enhancers in Arntl -/- macrophages as compared to
      wild-type cells. Expression of Nr1d1 and Nr1d2, encoding RevErb transcription
      factors, which repress enhancer RNA expression, was significantly decreased in
      Arntl -/- macrophages. Moreover, the level of H3K27 acetylation was increased by
      Arntl deletion at RevErb-dependent eRNA-expressing enhancers. These results
      suggest that Bmal1 controls KLA-responsive enhancers, in part by regulating
      RevErb-directed eRNA transcription. Taken together, the results of this study
      show that the clock transcription factor network containing Bmal1 controls the
      inflammatory responses of macrophages by regulating the epigenetic states of
      enhancers.

PMID- 28765525
TI  - Hole-phonon coupling effect on the band dispersion of organic molecular
      semiconductors.
AB  - The dynamic interaction between the traveling charges and the molecular
      vibrations is critical for the charge transport in organic semiconductors.
      However, a direct evidence of the expected impact of the charge-phonon coupling
      on the band dispersion of organic semiconductors is yet to be provided. Here, we
      report on the electronic properties of rubrene single crystal as investigated by
      angle resolved ultraviolet photoelectron spectroscopy. A gap opening and kink
      like features in the rubrene electronic band dispersion are observed. In
      particular, the latter results in a large enhancement of the hole effective mass
      (> 1.4), well above the limit of the theoretical estimations. The results are
      consistent with the expected modifications of the band structures in organic
      semiconductors as introduced by hole-phonon coupling effects and represent an
      important experimental step toward the understanding of the charge localization
      phenomena in organic materials.The charge transport properties in organic
      semiconductors are affected by the impact of molecular vibrations, yet it has
      been challenging to quantify them to date. Here, Bussolotti et al. provide direct
      experimental evidence on the band dispersion modified by molecular vibrations in
      a rubrene single crystal.

PMID- 28765526
TI  - CDHR1 mutations in retinal dystrophies.
AB  - We report ophthalmic and genetic findings in patients with autosomal recessive
      retinitis pigmentosa (RP), cone-rod dystrophy (CRD) or cone dystrophy (CD)
      harboring potential pathogenic variants in the CDHR1 gene. Detailed ophthalmic
      examination was performed in seven sporadic and six familial subjects. Mutation
      screening was done using a customized next generation sequencing panel targeting
      105 genes implicated in inherited retinal disorders. In one family, homozygosity
      mapping with subsequent candidate gene analysis was performed. Stringent
      filtering for rare and potentially disease causing variants following a model of
      autosomal recessive inheritance led to the identification of eleven different
      CDHR1 variants in nine index cases. All variants were novel at the time of their
      identification. In silico analyses confirmed their pathogenic potential. Minigene
      assays were performed for two non-canonical splice site variants and revealed
      missplicing for the mutant alleles. Mutations in CDHR1 are a rare cause of
      retinal dystrophy. Our study further expands the mutational spectrum of this gene
      and the associated clinical presentation.

PMID- 28765527
TI  - Calcium Ion Induced Structural Changes Promote Dimerization of Secretagogin,
      Which Is Required for Its Insulin Secretory Function.
AB  - Secretagogin (SCGN), a hexa EF-hand calcium binding protein, plays key roles in
      insulin secretion in pancreatic beta-cells. It is not yet understood how the
      binding of Ca2+ to human SCGN (hSCGN) promotes secretion. Here we have addressed
      this question, using mass spectrometry combined with a disulfide searching
      algorithm DBond. We found that the binding of Ca2+ to hSCGN promotes the
      dimerization of hSCGN via the formation of a Cys193-Cys193 disulfide bond.
      Hydrogen/deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics
      studies revealed that Ca2+ binding to the EF-hands of hSCGN induces significant
      structural changes that affect the solvent exposure of N-terminal region, and
      hence the redox sensitivity of the Cys193 residue. These redox sensitivity
      changes were confirmed using biotinylated methyl-3-nitro-4-(piperidin-1
      ylsulfonyl) benzoate (NPSB-B), a chemical probe that specifically labels reactive
      cysteine sulfhydryls. Furthermore, we found that wild type hSCGN overexpression
      promotes insulin secretion in pancreatic beta cells, while C193S-hSCGN inhibits
      it. These findings suggest that insulin secretion in pancreatic cells is
      regulated by Ca2+ and ROS signaling through Ca2+-induced structural changes
      promoting dimerization of hSCGN.

PMID- 28765528
TI  - Pdx1-Cre-driven conditional gene depletion suggests PAK4 as dispensable for mouse
      pancreas development.
AB  - Constitutive depletion of p21-activated kinase 4 (PAK4) in the mouse causes
      embryonic lethality associated with heart and brain defects. Given that
      conventional gene depletion of PAK1 or PAK3 caused functional deficits in the
      mouse pancreas, while gene depletion of PAK5 or PAK6 did not, we asked if PAK4
      might have a functional role in pancreas development. We therefore introduced
      conditional, Pdx1-Cre-mediated, pancreatic PAK4 gene depletion in the mouse,
      verified by loss of PAK4 protein expression in the pancreas. PAK4 knock-out (KO)
      mice were born at Mendelian ratios in both genders. Further, morphological and
      immunohistochemical examinations and quantifications indicated that exocrine,
      endocrine and ductal compartments retained the normal proportions and
      distributions upon PAK4 gene depletion. In addition, body weight records and a
      glucose tolerance test revealed no differences between WT and PAK4 KO mice.
      Together, this suggests that PAK4 is dispensable for mouse pancreas development.
      This will facilitate future use of our Pdx1-Cre-driven conditional PAK4 KO mouse
      model for testing in vivo potential functions of PAK4 in pancreatic disease
      models such as for pancreatitis and different pancreatic cancer forms.

PMID- 28765530
TI  - Risk factors for postoperative haemorrhage after total thyroidectomy: clinical
      results based on 2,678 patients.
AB  - The aim of this study was to analyse postoperative haemorrhage (POH) after a
      total thyroidectomy and explore the possible risk factors. Records of patients
      receiving a total thyroidectomy were reviewed and analysed for risk factors of
      POH. From the 2,678 patients in this study, a total of 39 patients had POH,
      representing an incidence of 1.5%. The majority (59.0%) of POH events occurred
      within four hours after surgery. Arterial haemorrhage was the primary cause of
      POH and was identifiable prior to venous bleeding, making it the first sign of
      POH. A univariate analysis revealed an association between POH, certain disease
      factors and BMI, but only a BMI greater than 30 was found to significantly
      increase the risk of POH (almost 6-fold). At the first sign of POH, all patients
      showed an obvious red drainage, and 92.3% of the patients had neck swelling. In
      summary, arterial bleeding is the main cause and first sign of postoperative
      haemorrhage, as it starts earlier than venous bleeding. A BMI greater than 30
      significantly increases the risk of neck haematoma.

PMID- 28765529
TI  - Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive
      Statin Treatment in Diabetes.
AB  - Residual atherothrombotic risk remains higher in patients with versus without
      diabetes mellitus (DM) despite statin therapy. The underlying mechanisms are
      unclear. This is a retrospective post-hoc analysis of the YELLOW II trial,
      comparing patients with and without DM (non-DM) who received rosuvastatin 40 mg
      for 8-12 weeks and underwent intracoronary multimodality imaging of an
      obstructive nonculprit lesion, before and after therapy. In addition, blood
      samples were drawn to assess cholesterol efflux capacity (CEC) and changes in
      gene expression in peripheral blood mononuclear cells (PBMC). There was a
      significant reduction in low density lipoprotein-cholesterol (LDL-C), an increase
      in CEC and beneficial changes in plaque morphology including increase in fibrous
      cap thickness and decrease in the prevalence of thin cap fibro-atheroma by
      optical coherence tomography in DM and non-DM patients. While differential gene
      expression analysis did not demonstrate differences in PBMC transcriptome between
      the two groups on the single-gene level, weighted gene coexpression network
      analysis revealed two modules of coexpressed genes associated with DM, Collagen
      Module and Platelet Module, related to collagen catabolism and platelet function
      respectively. Bayesian network analysis revealed key driver genes within these
      modules. These transcriptomic findings might provide potential mechanisms
      responsible for the higher cardiovascular risk in DM patients.

PMID- 28765531
TI  - Neuronal patterning of the tubular collar cord is highly conserved among
      enteropneusts but dissimilar to the chordate neural tube.
AB  - A tubular nervous system is present in the deuterostome groups Chordata
      (cephalochordates, tunicates, vertebrates) and in the non-chordate Enteropneusta.
      However, the worm-shaped enteropneusts possess a less complex nervous system
      featuring only a short hollow neural tube, whereby homology to its chordate
      counterpart remains elusive. Since the majority of data on enteropneusts stem
      from the harrimaniid Saccoglossus kowalevskii, putative interspecific variations
      remain undetected resulting in an unreliable ground pattern that impedes homology
      assessments. In order to complement the missing data from another enteropneust
      family, we investigated expression of key neuronal patterning genes in the
      ptychoderid Balanoglossus misakiensis. The collar cord of B. misakiensis shows
      anterior Six3/6 and posterior Otx + Engrailed expression, in a region
      corresponding to the chordate brain. Neuronal Nk2.1/Nk2.2 expression is absent.
      Interestingly, we found median Dlx and lateral Pax6 expression domains, i.e., a
      condition that is reversed compared to chordates. Comparative analyses reveal
      that adult nervous system patterning is highly conserved among the enteropneust
      families Harrimaniidae, Spengelidae and Ptychoderidae. BmiDlx and BmiPax6 have no
      corresponding expression domains in the chordate brain, which may be indicative
      of independent acquisition of a tubular nervous system in Enteropneusta and
      Chordata.

PMID- 28765532
TI  - Physarum machines imitating a Roman road network: the 3D approach.
AB  - Physarum Polycephalum is a single cell visible by unaided eye. This is a
      plasmodial, vegetative stage of acellular slime mould. This single cell has
      myriad of nuclei which contribute to a network of bio-chemical oscillators
      responsible for the slime mould's distributed sensing, concurrent information
      processing and decision making, and parallel actuation. When presented with a
      spatial configuration of sources of nutrients, the slime mould spans the sources
      with networks of its protoplasmic tube. These networks belong to a family of
      planar proximity graphs. The protoplasmic networks also show a degree of
      similarity to vehicular transport networks. Previously, we have shown that the
      foraging behaviour of the slime mould can be applied in archaeological research
      to complement and enhance conventional geographic information system tools. The
      results produced suffered from limitation of a flat substrate: transport routes
      imitated by the slime mould did not reflect patterns of elevations. To overcome
      the limitation of the 'flat world' we constructed a three-dimensional model of
      Balkans. In laboratory experiments and computer modelling we uncovered patterns
      of the foraging behaviour that might shed a light onto development of Roman roads
      in the Balkans during the imperial period (1st century BC - 4th century AD).

PMID- 28765533
TI  - Development of an integrated Monte Carlo model for glioblastoma multiforme
      treated with boron neutron capture therapy.
AB  - Glioblastomas (GBM) are notorious for their high fatality rate. Boron Neutron
      Capture Therapy (BNCT) being a biochemically targeted type of radiotherapy is a
      potent modality for GBM. In the current work, a BNCT treatment modelling
      framework for GBM was developed. Optimal Clinical Target Volume (CTV) margins for
      GBM-BNCT and the BNCT efficacy have been investigated. The model integrated a
      cell-based dosimetry model, an in-house-developed epithermal neutron beam model
      and previously-developed Microscopic Extension Probability (MEP) model. The
      system was defined as a cubic ICRP-brain phantom divided into 20 MUm side voxels.
      The corresponding 10B concentrations in GBM and normal brain cells were applied.
      The in-silico model was irradiated with the epithermal neutron beam using 2 and
      2.5 cm CTV margins. Results from the cell-based dosimetry and the MEP models were
      combined to calculate GBM cell survival fractions (SF) post BNCT and compared to
      x-ray radiotherapy (XRT) SFs. Compared to XRT, the SF within the beam decreased
      by five orders of magnitudes and the total SF was reduced three times following
      BNCT. CTV extension by 0.5 cm reduced the SF by additional (53.8 +/- 0.3)%. In
      conclusion, BNCT results in a more efficient cell kill. The extension of the CTV
      margin, however, may not increase the treatment outcome significantly.

PMID- 28765534
TI  - Bacteriophages as potential new mammalian pathogens.
AB  - Increased intestinal permeability and translocation of gut bacteria trigger
      various polyaetiological diseases associated with chronic inflammation and
      underlie a variety of poorly treatable pathologies. Previous studies have
      established a primary role of the microbiota composition and intestinal
      permeability in such pathologies. Using a rat model, we examined the effects of
      exposure to a bacteriophage cocktail on intestinal permeability and relative
      abundance of taxonomic units in the gut bacterial community. There was an
      increase in markers of impaired gut permeability, such as the lactulose/mannitol
      ratio, plasma endotoxin concentrations, and serum levels of inflammation-related
      cytokines, following the bacteriophage challenge. We observed significant
      differences in the alpha diversity of faecal bacterial species and found that
      richness and diversity index values increased following the bacteriophage
      challenge. There was a reduction in the abundance of Blautia, Catenibacterium,
      Lactobacillus, and Faecalibacterium species and an increase in Butyrivibrio,
      Oscillospira and Ruminococcus after bacteriophage administration. These findings
      provide novel insights into the role of bacteriophages as potentially pathogenic
      for mammals and their possible implication in the development of diseases
      associated with increased intestinal permeability.

PMID- 28765535
TI  - A highly attenuating and frequency tailorable annular hole phononic crystal for
      surface acoustic waves.
AB  - Surface acoustic wave (SAW) devices are widely used for signal processing,
      sensing and increasingly for lab-on-a-chip applications. Phononic crystals can
      control the propagation of SAW, analogous to photonic crystals, enabling
      components such as waveguides and cavities. Here we present an approach for the
      realisation of robust, tailorable SAW phononic crystals, based on annular holes
      patterned in a SAW substrate. Using simulations and experiments, we show that
      this geometry supports local resonances which create highly attenuating phononic
      bandgaps at frequencies with negligible coupling of SAWs into other modes, even
      for relatively shallow features. The enormous bandgap attenuation is up to an
      order-of-magnitude larger than that achieved with a pillar phononic crystal of
      the same size, enabling effective phononic crystals to be made up of smaller
      numbers of elements. This work transforms the ability to exploit phononic
      crystals for developing novel SAW device concepts, mirroring contemporary
      progress in photonic crystals.The control and manipulation of propagating sound
      waves on a surface has applications in on-chip signal processing and sensing.
      Here, Ash et al. deviate from standard designs and fabricate frequency tailorable
      phononic crystals with an order-of-magnitude increase in attenuation.

PMID- 28765536
TI  - PRR2, a pseudo-response regulator, promotes salicylic acid and camalexin
      accumulation during plant immunity.
AB  - Calcium signalling mediated by Calmodulin (CaM) and calmodulin-like (CML)
      proteins is critical to plant immunity. CaM and CML regulate a wide range of
      target proteins and cellular responses. While many CaM-binding proteins have been
      identified, few have been characterized for their specific role in plant
      immunity. Here, we report new data on the biological function of a CML
      interacting partner, PRR2 (PSEUDO-RESPONSE REGULATOR 2), a plant specific
      transcription factor. Until now, the physiological relevance of PRR2 remained
      largely unknown. Using a reverse genetic strategy in A. thaliana, we identified
      PRR2 as a positive regulator of plant immunity. We propose that PRR2 contributes
      to salicylic acid (SA)-dependent responses when challenged with the
      phytopathogenic bacterium Pseudomonas syringae. PRR2 is transcriptionally
      upregulated by SA and P. syringae, enhances SA biosynthesis and SA signalling
      responses; e.g. in response to P. syringae, PRR2 induces the production of SA and
      the accumulation of the defence-related protein PR1. Moreover, PRR2
      overexpressing lines exhibit an enhanced production of camalexin, a phytoalexin
      that confers enhanced resistance against pathogens. Together, these data reveal
      the importance of PRR2 in plant immune responses against P. syringae and suggest
      a novel function for this particular plant specific transcription factor in plant
      physiology.

PMID- 28765537
TI  - PRDX2 in Myocyte Hypertrophy and Survival is Mediated by TLR4 in Acute Infarcted
      Myocardium.
AB  - Peroxiredoxin 2 (PRDX2) is an antioxidant and molecular chaperone that can be
      secreted from tumor cells. But the role of PRDX2 in acute myocardial infarction
      (AMI) is not clear. In the current study, we demonstrate the role of PRDX2 from
      clinical trials, H9c2 cells and in a mouse model. ELISA analysis shows that serum
      concentrations of VEGF and inflammatory factor IL-1beta, TNF-alpha and IL-6 were
      increased in AMI patients compared to a control group. The expression of PRDX2
      was also upregulated. In vivo experiments show that the expression of PRDX2
      inhibits hypoxia-induced oxidative stress injury to H9c2 cells. However, PRDX2
      expression promotes TLR4 mediated inflammatory factor expression and VEGF
      expression under hypoxia conditions. PRDX2 overexpression in H9c2 cells also
      promotes human endothelial cell migration, vasculogenic mimicry formation and
      myocardial hypertrophy related protein expression. The overexpression of PRDX2
      inhibits ROS level and myocardial injury after AMI but promotes inflammatory
      responses in vivo. Immunocytochemistry and immunofluorescence analysis show that
      overexpression of PRDX2 promotes angiogenesis and myocardial hypertrophy. Taken
      together, our results indicate that PRDX2 plays two roles in acute infarction -
      the promotion of cell survival and inflammatory myocardial hypertrophy.

PMID- 28765538
TI  - Metabonomics Approach to Assessing the Modulatory Effects of Kisspeptin-10 on
      Liver Injury Induced by Heat Stress in Rats.
AB  - The protective effects of Kisspeptin on heat-induced oxidative stress in rats
      were investigated by using a combination of biochemical parameters and
      metabonomics. Metabonomic analyses were performed using gas chromatography/mass
      spectrometry in conjunction with multivariate and univariate statistical
      analyses. At the end point of the heat stress experiment, histological
      observation, ultrastructural analysis and biochemical parameters were measured.
      Metabonomic analysis of liver tissue revealed that Kisspeptin mainly attenuated
      the alteration of purine metabolism and fatty acid metabolism pathways.
      Futhermore, Kisspeptin also increased the levels of GSH, T-AOC as well as SOD
      activities, and upregulated MDA levels. These results provide important
      mechanistic insights into the protective effects of Kisspeptin against heat
      induced oxidative stress.

PMID- 28765539
TI  - Bacterial membrane vesicles transport their DNA cargo into host cells.
AB  - Bacterial outer membrane vesicles (OMVs) are extracellular sacs containing
      biologically active products, such as proteins, cell wall components and toxins.
      OMVs are reported to contain DNA, however, little is known about the nature of
      this DNA, nor whether it can be transported into host cells. Our work
      demonstrates that chromosomal DNA is packaged into OMVs shed by bacteria during
      exponential phase. Most of this DNA was present on the external surfaces of OMVs,
      with smaller amounts located internally. The DNA within the internal compartments
      of Pseudomonas aeruginosa OMVs were consistently enriched in specific regions of
      the bacterial chromosome, encoding proteins involved in virulence, stress
      response, antibiotic resistance and metabolism. Furthermore, we demonstrated that
      OMVs carry DNA into eukaryotic cells, and this DNA was detectable by PCR in the
      nuclear fraction of cells. These findings suggest a role for OMV-associated DNA
      in bacterial-host cell interactions and have implications for OMV-based vaccines.

PMID- 28765540
TI  - Harvesting more grain zinc of wheat for human health.
AB  - Increasing grain zinc (Zn) concentration of cereals for minimizing Zn
      malnutrition in two billion people represents an important global humanitarian
      challenge. Grain Zn in field-grown wheat at the global scale ranges from 20.4 to
      30.5 mg kg-1, showing a solid gap to the biofortification target for human health
      (40 mg kg-1). Through a group of field experiments, we found that the low grain
      Zn was not closely linked to historical replacements of varieties during the
      Green Revolution, but greatly aggravated by phosphorus (P) overuse or
      insufficient nitrogen (N) application. We also conducted a total of 320-pair
      plots field experiments and found an average increase of 10.5 mg kg-1 by foliar
      Zn application. We conclude that an integrated strategy, including not only Zn
      responsive genotypes, but of a similar importance, Zn application and field N and
      P management, are required to harvest more grain Zn and meanwhile ensure better
      yield in wheat-dominant areas.

PMID- 28765541
TI  - In silico analyses of conservational, functional and phylogenetic distribution of
      the LuxI and LuxR homologs in Gram-positive bacteria.
AB  - LuxI and LuxR are key factors that drive quorum sensing (QS) in bacteria through
      secretion and perception of the signaling molecules e.g. N-Acyl homoserine
      lactones (AHLs). The role of these proteins is well established in Gram-negative
      bacteria for intercellular communication but remain under-explored in Gram
      positive bacteria where QS peptides are majorly responsible for cell-to-cell
      communication. Therefore, in the present study, we explored conservation,
      potential function, topological arrangements and evolutionarily aspects of these
      proteins in Gram-positive bacteria. Putative LuxI/LuxR containing proteins were
      retrieved using the domain-based strategy from InterPro v62.0 meta-database.
      Conservational analyses via multiple sequence alignment and domain showed that
      these are well conserved in Gram-positive bacteria and possess relatedness with
      Gram-negative bacteria. Further, Gene ontology and ligand-based functional
      annotation explain their active involvement in signal transduction mechanism via
      QS signaling molecules. Moreover, Phylogenetic analyses (LuxI, LuxR, LuxI + LuxR
      and 16s rRNA) revealed horizontal gene transfer events with significant
      statistical support among Gram-positive and Gram-negative bacteria. This in
      silico study offers a detailed overview of potential LuxI/LuxR distribution in
      Gram-positive bacteria (mainly Firmicutes and Actinobacteria) and their
      functional role in QS. It would further help in understanding the extent of
      interspecies communications between Gram-positive and Gram-negative bacteria
      through QS signaling molecules.

PMID- 28765542
TI  - Ionic liquid accelerates the crystallization of Zr-based metal-organic
      frameworks.
AB  - The Zr-based metal-organic frameworks are generally prepared by solvothermal
      procedure. To overcome the slow kinetics of nucleation and crystallization of Zr
      based metal-organic frameworks is of great interest and challenging. Here, we
      find that an ionic liquid as solvent can significantly accelerate the formation
      of Zr-based metal-organic frameworks at room temperature. For example, the
      reaction time is shortened to 0.5 h in 1-hexyl-3-methylimidazolium chloride for
      Zr-based metal-organic framework formation, while that in the conventional
      solvent N,N-dimethylformamide needs at least 120 h. The reaction mechanism was
      investigated in situ by 1H nuclear magnetic resonance, spectroscopy synchrotron
      small angle X-ray scattering and X-ray absorption fine structure. This rapid, low
      energy, and facile route produces Zr-based metal-organic framework nanoparticles
      with small particle size, missing-linker defects and large surface area, which
      can be used as heterogeneous catalysts for Meerwein-Ponndorf-Verley
      reaction.Crystallization kinetics of metal-organic frameworks in conventional
      organic solvents are usually very slow. Here, the authors show that an ionic
      liquid medium accelerates considerably the formation of Zr-based metal-organic
      frameworks that are active catalysts in the Meerwein-Ponndorf-Verley reaction.

PMID- 28765544
TI  - Cloaking of Thermoelectric Transport.
AB  - The ability to control electromagnetic fields, heat currents, electric currents,
      and other physical phenomena by coordinate transformation methods has resulted in
      novel functionalities, such as cloaking, field rotations, and concentration
      effects. Transformation optics, as the underlying mathematical tool, has proven
      to be a versatile approach to achieve such unusual outcomes relying on materials
      with highly anisotropic and inhomogeneous properties. Most applications and
      designs thus far have been limited to functionalities within a single physical
      domain. Here we present transformation optics applied to thermoelectric
      phenomena, where thermal and electric flows are coupled via the Seebeck
      coefficient. Using laminates, we describe a thermoelectric cloak capable of
      hiding objects from thermoelectric flow. Our calculations show that such a cloak
      does not depend on the particular boundary conditions and can also operate in
      different single domain regimes. These proof-of-principle results constitute a
      significant step forward towards finding unexplored ways to control and
      manipulate coupled transport.

PMID- 28765543
TI  - Descemet's Membrane Supports Corneal Endothelial Cell Regeneration in Rabbits.
AB  - Descemet's membrane (DM) helps maintain phenotype and function of corneal
      endothelial cells under physiological conditions, while little is known about the
      function of DM in corneal endothelial wound healing process. In the current
      study, we performed in vivo rabbit corneal endothelial cell (CEC) injury via CEC
      scraping, in which DM remained intact after CECs removal, or via DM stripping, in
      which DM was removed together with CECs. We found rabbit corneas in the CEC
      scraping group healed with transparency restoration, while there was posterior
      fibrosis tissue formation in the corneas after DM stripping on day 14. Following
      CEC scraping on day 3, cells that had migrated toward the central cornea
      underwent a transient fibrotic endothelial-mesenchymal transition (EMT) which was
      reversed back to an endothelial phenotype on day 14. However, in the corneas
      injured via DM stripping, most of the cells in the posterior fibrosis tissue did
      not originate from the corneal endothelium, and they maintained fibroblastic
      phenotype on day 14. We concluded that corneal endothelial wound healing in
      rabbits has different outcomes depending upon the presence or absence of
      Descemet's membrane. Descemet's membrane supports corneal endothelial cell
      regeneration in rabbits after endothelial injury.

PMID- 28765545
TI  - The prospect of rising in rank is key to long-term stability in Tibetan macaque
      society.
AB  - One of the most fundamental questions in behavioural biology is why societies can
      persist for a long period of time. While researchers in animal behaviour have
      been hindered by a lack of an aggregate measure (such as social mobility) to
      quantify the dynamics of animal societies, researchers in social sciences have
      been challenged by the complexity and diversity of human societies. As a result,
      direct empirical evidence is still lacking for the hypothesized causal
      relationship between social mobility and social stability. Here we attempt to
      fill the void by examining a much simpler society in the Tibetan macaque (Macaca
      thibetana), which we have tracked for 30 consecutive years. By testing two group
      level hypotheses based on benefit-cost analysis and social stratification, we
      show the first quantitative evidence that an annual 2-to-1 stay/change ratio in
      the hierarchy with a 3-to-1 upward/downward ratio in intragenerational social
      mobility provides a substantive expected benefit for adult members to stay in the
      group and wait for their chances to advance. Furthermore, using a Markov
      transition matrix constructed from empirical data, we demonstrate that the 3-to-1
      upward/downward ratio could lead to long-term structural stability in Tibetan
      macaque society.

PMID- 28765547
TI  - Simultaneous determination of hydrophilic and lipophilic constituents in herbal
      medicines using directly-coupled reversed-phase and hydrophilic interaction
      liquid chromatography-tandem mass spectrometry.
AB  - Limitations in the separation ability of conventional liquid chromatography
      system remains a challenge in developing a versatile method for simultaneously
      determining both hydrophilic and lipophilic constituents in herbal medicines
      (HMs). To measure compounds covering a broad polarity span in HMs, we developed a
      directly-coupled reversed-phase and hydrophilic interaction liquid chromatography
      tandem mass spectrometry system. Samples were firstly separated according to
      lipophilicity by using a C18 column. Utilizing a T-piece as connector, the eluent
      was then pumped into an amide column to get further separation that mainly based
      on the hydrogen bonding effects. Dan-Qi pair, an extensively used herb-combined
      prescription in China, was selected to test the practicability and performance of
      the established system. A total of 27 components, containing 9 hydrophilic and 18
      lipophilic constituents, were simultaneously determined using a schedule multiple
      reaction monitoring method in 15 min. Up to 69.9% content could be monitored in
      one injection in Dan-Qi pair extract, showing a significant advantage over
      previous methods. The proposed method was expected to benefit the controllability
      of herbal medicines.

PMID- 28765546
TI  - Integrative whole-genome sequence analysis reveals roles of regulatory mutations
      in BCL6 and BCL2 in follicular lymphoma.
AB  - The contribution of mutations in regulatory regions to tumorigenesis has been the
      subject of many recent studies. We propose a new framework for integrative
      analysis of genome-wide sequencing data by considering diverse genetic
      information. This approach is applied to study follicular lymphoma (FL), a
      disease for which little is known about the contribution of regulatory gene
      mutations. Results from a test FL cohort revealed three novel highly recurrent
      regulatory mutation blocks near important genes implicated in FL, BCL6 and BCL2.
      Similar findings were detected in a validation FL cohort. We also found
      transcription factors (TF) whose binding may be disturbed by these mutations in
      FL: disruption of FOX TF family near the BCL6 promoter may result in reduced BCL6
      expression, which then increases BCL2 expression over that caused by BCL2 gene
      translocation. Knockdown experiments of two TF hits (FOXD2 or FOXD3) were
      performed in human B lymphocytes verifying that they modulate BCL6/BCL2 according
      to the computationally predicted effects of the SNVs on TF binding. Overall, our
      proposed integrative analysis facilitates non-coding driver identification and
      the new findings may enhance the understanding of FL.

PMID- 28765548
TI  - Excitation-dependent fluorescence from atomic/molecular layer deposited sodium
      uracil thin films.
AB  - Atomic/molecular layer deposition (ALD/MLD) offers unique possibilities in the
      fabrication of inorganic-organic thin films with novel functionalities.
      Especially, incorporating nucleobases in the thin-film structures could open new
      avenues in the development of bio-electronic and photonic devices. Here we report
      an intense blue and widely excitation-dependent fluorescence in the visible
      region for ALD/MLD fabricated sodium-uracil thin films, where the crystalline
      network is formed from hydrogen-bonded uracil molecules linked via Na atoms. The
      excitation-dependent fluorescence is caused by the red-edge excitation shift
      (REES) effect taking place in the red-edge of the absorption spectrum, where the
      spectral relaxation occurs in continuous manner as demonstrated by the time
      resolved measurements.

PMID- 28765549
TI  - Improving satellite-based PM2.5 estimates in China using Gaussian processes
      modeling in a Bayesian hierarchical setting.
AB  - Using satellite-based aerosol optical depth (AOD) measurements and statistical
      models to estimate ground-level PM2.5 is a promising way to fill the areas that
      are not covered by ground PM2.5 monitors. The statistical models used in previous
      studies are primarily Linear Mixed Effects (LME) and Geographically Weighted
      Regression (GWR) models. In this study, we developed a new regression model
      between PM2.5 and AOD using Gaussian processes in a Bayesian hierarchical
      setting. Gaussian processes model the stochastic nature of the spatial random
      effects, where the mean surface and the covariance function is specified. The
      spatial stochastic process is incorporated under the Bayesian hierarchical
      framework to explain the variation of PM2.5 concentrations together with other
      factors, such as AOD, spatial and non-spatial random effects. We evaluate the
      results of our model and compare them with those of other, conventional
      statistical models (GWR and LME) by within-sample model fitting and out-of-sample
      validation (cross validation, CV). The results show that our model possesses a CV
      result (R2 = 0.81) that reflects higher accuracy than that of GWR and LME (0.74
      and 0.48, respectively). Our results indicate that Gaussian process models have
      the potential to improve the accuracy of satellite-based PM2.5 estimates.

PMID- 28765550
TI  - Linearly polarized GHz magnetization dynamics of spin helix modes in the
      ferrimagnetic insulator Cu2OSeO3.
AB  - Linear dichroism - the polarization dependent absorption of electromagnetic waves
      is routinely exploited in applications as diverse as structure determination of
      DNA or polarization filters in optical technologies. Here filamentary absorbers
      with a large length-to-width ratio are a prerequisite. For magnetization dynamics
      in the few GHz frequency regime strictly linear dichroism was not observed for
      more than eight decades. Here, we show that the bulk chiral magnet Cu2OSeO3
      exhibits linearly polarized magnetization dynamics at an unexpectedly small
      frequency of about 2 GHz at zero magnetic field. Unlike optical filters that are
      assembled from filamentary absorbers, the magnet is shown to provide linear
      polarization as a bulk material for an extremely wide range of length-to-width
      ratios. In addition, the polarization plane of a given mode can be switched by 90
      degrees  via a small variation in width. Our findings shed a new light on
      magnetization dynamics in that ferrimagnetic ordering combined with antisymmetric
      exchange interaction offers strictly linear polarization and cross-polarized
      modes for a broad spectrum of sample shapes at zero field. The discovery allows
      for novel design rules and optimization of microwave-to-magnon transduction in
      emerging microwave technologies.

PMID- 28765551
TI  - Pair distribution function analysis of sulfide glassy electrolytes for all-solid
      state batteries: Understanding the improvement of ionic conductivity under
      annealing condition.
AB  - In general, the ionic conductivity of sulfide glasses decreases with their
      crystallization, although it increases for a few sulphide glasses owing to the
      crystallization of a highly conductive new phase (e.g., Li7P3S11: 70Li2S-30P2S5).
      We found that the ionic conductivity of 75Li2S-25P2S5 sulfide glass, which
      consists of glassy and crystalline phases, is improved by optimizing the
      conditions of the heat treatment, i.e., annealing. A different mechanism of high
      ionic conductivity from the conventional mechanism is expected in the glassy
      phase. Here, we report the glassy structure of 75Li2S-25P2S5 immediately before
      the crystallization by using the differential pair distribution function (d-PDF)
      analysis of high-energy X-ray diffraction. Even though the ionic conductivity
      increases during the optimum annealing, the d-PDF analysis indicated that the
      glassy structure undergoes no structural change in the sulfide glass-ceramic
      electrolyte at a crystallinity of 33.1%. We observed the formation of a
      nanocrystalline phase in the X-ray and electron diffraction patterns before the
      crystallization, which means that Bragg peaks were deformed. Thus, the ionic
      conductivity in the mixture of glassy and crystalline phases is improved by the
      coexistence of the nanocrystalline phase.

PMID- 28765553
TI  - Order-disorder transition in active nematic: A lattice model study.
AB  - We introduce a lattice model for active nematic composed of self-propelled apolar
      particles, study its different ordering states in the density-temperature
      parameter space, and compare with the corresponding equilibrium model. The active
      particles interact with their neighbours within the framework of the Lebwohl
      Lasher model, and move anisotropically along their orientation to an unoccupied
      nearest neighbour lattice site. An interplay of the activity, thermal
      fluctuations and density gives rise distinct states in the system. For a fixed
      temperature, the active nematic shows a disordered isotropic state, a locally
      ordered inhomogeneous mixed state, and bistability between the inhomogeneous
      mixed and a homogeneous globally ordered state in different density regime. In
      the low temperature regime, the isotropic to the inhomogeneous mixed state
      transition occurs with a jump in the order parameter at a density less than the
      corresponding equilibrium disorder-order transition density. Our analytical
      calculations justify the shift in the transition density and the jump in the
      order parameter. We construct the phase diagram of the active nematic in the
      density-temperature plane.

PMID- 28765552
TI  - Antitumoral effects of gammaCdcPLI, a PLA2 inhibitor from Crotalus durissus
      collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell.
AB  - Phospholipases A2 (PLA2s) overexpression is closely associated with the malignant
      potential of breast cancers. Here, we showed for the first the antitumoral
      effects of gammaCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via
      PI3K/Akt pathway on MDA-MB-231 cell. Firstly, gammaCdcPLI was more cytotoxic to
      MDA-MB-231 breast cancer cells than other cell lines (MCF-7, HeLa, PC3 and A549)
      and did not affect the viability of non-tumorigenic breast cell (MCF 10A). In
      addition, gammaCdcPLI induced modulation of important mediators of apoptosis
      pathways such as p53, MAPK-ERK, BIRC5 and MDM2. gammaCdcPLI decreased MDA-MB-231
      adhesion, migration and invasion. Interestingly, the gammaCdcPLI also inhibited
      the adhesion and migration of endothelial cells and blocked angiogenesis by
      inhibiting tube formation by HUVECs in vitro and sprouting elongation on aortic
      ring assay ex vivo. Furthermore, gammaCdcPLI reduced the production of vascular
      endothelial growth factor (VEGF). gammaCdcPLI was also able to decrease PGE2
      levels in MDA-MB-231 and inhibited gene and protein expression of the PI3K/Akt
      pathway. In conclusion, gammaCdcPLI showed in vitro antitumoral, antimestatatic
      and anti-angiogenic potential effects and could be an attractive approach for
      futures studies in cancer therapy.

PMID- 28765554
TI  - Non-peptide guided auto-secretion of recombinant proteins by super-folder green
      fluorescent protein in Escherichia coli.
AB  - Protein secretion in Escherichia coli is usually led by a signal peptide that
      targets the protein to specific secretory pathways. In this study, we
      demonstrated that the superfolder green fluorescent protein (sfGFP) could be
      served as a non-signal peptide to guide protein auto-secretion in E. coli. This
      auto-secretion was characterized as a three-step process through the sub-cellular
      localization analysis: inner membrane trans-location followed by anchoring at
      outer membrane, and then being released into culture media. We further determined
      that the beta-barrel structure and net negative charges of sfGFP played important
      roles in its auto-extracellular secretion property. Using sfGFP as a carrier,
      heterologous proteins ranging from peptide to complex protein, including
      antibacterial peptide PG4, endo-beta-N-acethylglucosamindase H (Endo H), human
      arginase-1 (ARG1), and glutamate decarboxylase (GAD) were all successfully
      expressed and secreted extracellularly when fused to the carboxyl end of sfGFP.
      Besides facilitating the extracellular secretion, sfGFP fusion proteins can also
      be correctly folded and formed the active complex protein structure, including
      the trimetric human ARG1 and homo-hexametric GAD. This is the first report that
      sfGFP can guide the secretion of recombinant proteins out of the cells from
      cytoplasm in E. coli without affecting their conformation and function.

PMID- 28765555
TI  - Body mass index, waist-to-hip ratio and late outcomes: a report from the Shanghai
      Breast Cancer Survival Study.
AB  - Obesity has been well studied in relation to breast cancer survival. However, the
      associations of post-diagnosis obesity and late outcomes (>=5 years after
      diagnosis) have been much less studied. A total of 4062 5-year disease-free
      patients were recruited from the Shanghai Breast Cancer Survival Study, a
      longitudinal study of patients diagnosed during 2002-2006. Cox proportional
      hazard model with restricted cubic spline were used to evaluate the potential non
      linear associations of post-diagnosis body mass index (BMI) and waist-to-hip
      ratio (WHR) with late all-cause mortality and late recurrence. While no
      significant association was observed for post-diagnosis BMI or WHR with late
      recurrence; a U-shaped association was observed for the two measures with late
      all-cause death. Women with BMI of 25.0 kg/m2 or WHR of 0.83 were at the lowest
      risk of late all-cause mortality, whereas those with BMI beyond the range of 22.1
      28.7 kg/m2 or WHR beyond the range of 0.81-0.86 had a higher risk. ER, stage or
      menopausal status did not modify the effect of post-diagnosis BMI or WHR on the
      outcomes. In conclusion, post-diagnosis BMI and WHR, as indicators of overall and
      central obesity respectively, were associated with late all-cause mortality in U
      shaped pattern among long-term breast cancer survivors.

PMID- 28765556
TI  - Antimicrobial spray nanocoating of supramolecular Fe(III)-tannic acid metal
      organic coordination complex: applications to shoe insoles and fruits.
AB  - Numerous coating strategies are available to control the surface properties and
      confer new properties to substrates for applications in energy, environment,
      biosystems, etc., but most have the intrinsic limitations in the practical
      setting: (1) highly specific interactions between coating materials and target
      surfaces are required for stable and durable coating; (2) the coating of bulk
      substrates, such as fruits, is time-consuming or is not achievable in the
      conventional solution-based coating. In this respect, material-independent and
      rapid coating strategies are highly demanded. We demonstrate spray-assisted
      nanocoating of supramolecular metal-organic complexes of tannic acid and ferric
      ions. The spray coating developed is material-independent and extremely rapid (<5
      sec), allowing for coating of commodity goods, such as shoe insoles and fruits,
      in the controlled fashion. For example, the spray-coated mandarin oranges and
      strawberries show significantly prolonged post-harvest shelf-life, suggesting
      practical potential in edible coating of perishable produce.

PMID- 28765557
TI  - The Voltage-Dependent Anion Channels (VDAC) of Mycobacterium avium phagosome are
      associated with bacterial survival and lipid export in macrophages.
AB  - Mycobacterium avium subsp. hominissuis is associated with infection of
      immunocompromised individuals as well as patients with chronic lung disease. M.
      avium infects macrophages and actively interfere with the host killing machinery
      such as apoptosis and autophagy. Bacteria alter the normal endosomal trafficking,
      prevent the maturation of phagosomes and modify many signaling pathways inside of
      the macrophage by secreting effector molecules into the cytoplasm. To investigate
      whether M. avium needs to attach to the internal surface of the vacuole membrane
      before releasing efferent molecules, vacuole membrane proteins were purified and
      binding to the surface molecules present in intracellular bacteria was evaluated.
      The voltage-dependent anion channels (VDAC) were identified as components of M.
      avium vacuoles in macrophages. M. avium mmpL4 proteins were found to bind to VDAC
      1 protein. The inactivation of VDAC-1 function either by pharmacological means or
      siRNA lead to significant decrease of M. avium survival. Although, we could not
      establish a role of VDAC channels in the transport of known secreted M. avium
      proteins, we demonstrated that the porin channels are associated with the export
      of bacterial cell wall lipids outside of vacuole. Suppression of the host
      phagosomal transport systems and the pathogen transporter may serve as
      therapeutic targets for infectious diseases.

PMID- 28765558
TI  - Cardiac spheroids as promising in vitro models to study the human heart
      microenvironment.
AB  - Three-dimensional in vitro cell systems are a promising alternative to animals to
      study cardiac biology and disease. We have generated three-dimensional in vitro
      models of the human heart ("cardiac spheroids", CSs) by co-culturing human
      primary or iPSC-derived cardiomyocytes, endothelial cells and fibroblasts at
      ratios approximating those present in vivo. The cellular organisation,
      extracellular matrix and microvascular network mimic human heart tissue. These
      spheroids have been employed to investigate the dose-limiting cardiotoxicity of
      the common anti-cancer drug doxorubicin. Viability/cytotoxicity assays indicate
      dose-dependent cytotoxic effects, which are inhibited by the nitric oxide
      synthase (NOS) inhibitor L-NIO, and genetic inhibition of endothelial NOS,
      implicating peroxynitrous acid as a key damaging agent. These data indicate that
      CSs mimic important features of human heart morphology, biochemistry and
      pharmacology in vitro, offering a promising alternative to animals and standard
      cell cultures with regard to mechanistic insights and prediction of toxic effects
      in human heart tissue.

PMID- 28765559
TI  - Model representations of kerogen structures: An insight from density functional
      theory calculations and spectroscopic measurements.
AB  - Molecular structures of kerogen control hydrocarbon production in unconventional
      reservoirs. Significant progress has been made in developing model
      representations of various kerogen structures. These models have been widely used
      for the prediction of gas adsorption and migration in shale matrix. However,
      using density functional perturbation theory (DFPT) calculations and vibrational
      spectroscopic measurements, we here show that a large gap may still remain
      between the existing model representations and actual kerogen structures,
      therefore calling for new model development. Using DFPT, we calculated Fourier
      transform infrared (FTIR) spectra for six most widely used kerogen structure
      models. The computed spectra were then systematically compared to the FTIR
      absorption spectra collected for kerogen samples isolated from Mancos, Woodford
      and Marcellus formations representing a wide range of kerogen origin and
      maturation conditions. Limited agreement between the model predictions and the
      measurements highlights that the existing kerogen models may still miss some key
      features in structural representation. A combination of DFPT calculations with
      spectroscopic measurements may provide a useful diagnostic tool for assessing the
      adequacy of a proposed structural model as well as for future model development.
      This approach may eventually help develop comprehensive infrared (IR)
      fingerprints for tracing kerogen evolution.

PMID- 28765560
TI  - Machine Learning-Assisted Network Inference Approach to Identify a New Class of
      Genes that Coordinate the Functionality of Cancer Networks.
AB  - Emerging evidence indicates the existence of a new class of cancer genes that act
      as "signal linkers" coordinating oncogenic signals between mutated and
      differentially expressed genes. While frequently mutated oncogenes and
      differentially expressed genes, which we term Class I cancer genes, are readily
      detected by most analytical tools, the new class of cancer-related genes, i.e.,
      Class II, escape detection because they are neither mutated nor differentially
      expressed. Given this hypothesis, we developed a Machine Learning-Assisted
      Network Inference (MALANI) algorithm, which assesses all genes regardless of
      expression or mutational status in the context of cancer etiology. We used 8807
      expression arrays, corresponding to 9 cancer types, to build more than 2 * 108
      Support Vector Machine (SVM) models for reconstructing a cancer network. We found
      that ~3% of ~19,000 not differentially expressed genes are Class II cancer gene
      candidates. Some Class II genes that we found, such as SLC19A1 and ATAD3B, have
      been recently reported to associate with cancer outcomes. To our knowledge, this
      is the first study that utilizes both machine learning and network biology
      approaches to uncover Class II cancer genes in coordinating functionality in
      cancer networks and will illuminate our understanding of how genes are modulated
      in a tissue-specific network contribute to tumorigenesis and therapy development.

PMID- 28765561
TI  - Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus
      Infection.
AB  - Dengue is the most common mosquito-transmitted viral infection for which an
      improved vaccine is still needed. Although nonstructural protein-1 (NS1)
      immunization can protect mice against dengue infection, molecular mimicry between
      NS1 and host proteins makes NS1-based vaccines challenging to develop. Based on
      the epitope recognized by the anti-NS1 monoclonal Ab (mAb) 33D2 which recognizes
      a conserved NS1 wing domain (NS1-WD) region but not host proteins, we synthesized
      a modified NS1-WD peptide to immunize mice. We found that both mAb 33D2 and
      modified NS1-WD peptide immune sera could induce complement-dependent lysis of
      dengue-infected but not un-infected cells in vitro. Furthermore, either active
      immunization with the modified NS1-WD peptide or passive transfer of mAb 33D2
      efficiently protected mice against all serotypes of dengue virus infection. More
      importantly, dengue patients with more antibodies recognized the modified NS1-WD
      peptide had less severe disease. Thus, the modified NS1-WD peptide is a promising
      dengue vaccine candidate.

PMID- 28765562
TI  - Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the
      highly selective enrichment of N-linked glycopeptides.
AB  - The low abundance of glycopeptides in biological samples makes it necessary to
      enrich them before further analysis. In this study, the polymeric hydrophilic
      ionic liquid-modified magnetic (Fe3O4@MPS@PMAC) nanoparticles were synthesized
      via a one-step reflux-precipitation polymerization. Owing to the excellent
      hydrophilicity and strong electrostatic interaction toward glycopeptides of the
      polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl]
      trimethylammonium chloride (MAC), the synthesized Fe3O4@MPS@PMAC nanoparticles
      exhibited outstanding performance in glycopeptide enrichment with high detection
      sensitivity (10 fmol), large binding capacity (100 MUg mg-1) and satisfied
      enrichment recovery (approximately 82%). Furthermore, the newly developed
      Fe3O4@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa
      exosome proteins. A total of 1274 glycopeptides from 536 glycoproteins were
      identified in three replicate analyses of 50 MUg of HeLa exosome proteins. These
      results demonstrate the potential of Fe3O4@MPS@PMAC nanoparticles for both
      glycoproteomic analysis and exosome research.

PMID- 28765563
TI  - Quantitative Proteomics of Cerebrospinal Fluid in Paediatric Pneumococcal
      Meningitis.
AB  - Streptococcus pneumoniae is responsible for diseases causing major global public
      health problems, including meningitis, pneumonia and septicaemia. Despite recent
      advances in antimicrobial therapy, pneumococcal meningitis remains a life
      threatening disease. Furthermore, long-term sequelae are a major concern for
      survivors. Hence, a better understanding of the processes occurring in the
      central nervous system is crucial to the development of more effective management
      strategies. We used mass spectrometry based quantitative proteomics to identify
      protein changes in cerebrospinal fluid from children with Streptococcus
      pneumoniae infection, compared with children admitted to hospital with bacterial
      meningitis symptoms but negative diagnosis. Samples were analysed, by label free
      proteomics, in two independent cohorts (cohort 1: cases (n = 8) and hospital
      controls (n = 4); cohort 2: cases (n = 8), hospital controls (n = 8)). Over 200
      human proteins were differentially expressed in each cohort, of which 65% were
      common to both. Proteins involved in the immune response and exosome signalling
      were significantly enriched in the infected samples. For a subset of proteins
      derived from the proteome analysis, we corroborated the proteomics data in a
      third cohort (hospital controls (n = 15), healthy controls (n = 5), cases (n =
      20)) by automated quantitative western blotting, with excellent agreement with
      our proteomics findings. Proteomics data are available via ProteomeXchange with
      identifier PXD004219.

PMID- 28765564
TI  - Acceleration of Batch-type Heterogeneous Ligand-free Suzuki-Miyaura Reactions
      with Polymer Composite Supported Pd Catalyst.
AB  - An efficient and recyclable palladium (II) catalyst supported on a double
      structured amphiphilic polymer composite was reported previously containing a
      polymer hydrogel within macroporous polystyrene (PS) microspheres. However, some
      critical questions have been unaddressed. First, the catalyst accelerated the
      heterogeneous ligand-free batch Suzuki-Miyaura reaction in a H2O/EtOH mixture
      solution at room temperature in the presence of air, which could be ascribed to
      the "on-water" effect taking place at the interface of the aqueous-organic and
      basic-aqueous phases created by sodium carbonate in H2O/EtOH. To this
      acceleration, the double-structured amphiphilic polymer composite can also
      contribute by providing hydrogels inside the macroporous PS that served as a
      microreactor. This microreactor allowed the reactions to quickly proceed across
      the two immiscible (i.e. aqueous-organic and basic-aqueous) phases. Moreover,
      hydrogels containing hydroxyl groups can also serve as phase-transfer catalysts
      (PTC) to promote the Suzuki reaction. Second, the deactivated catalyst recovered
      its initial catalytic activity after overnight air exposure. This observation
      indicates the importance of oxygen in the activation/deactivation of Pd metals,
      as determined by X-ray photoelectron spectroscopy (XPS) and X-ray diffraction
      (XRD) measurements which revealed different Pd oxidation states with various
      morphologies before and after Suzuki reactions.

PMID- 28765565
TI  - Telomerase reverse transcriptase promotes chemoresistance by suppressing
      cisplatin-dependent apoptosis in osteosarcoma cells.
AB  - Cisplatin is one of the most efficacious antimitotic drugs used in the treatment
      of a range of malignant tumors. However, treatment failures are common due to the
      development of chemoresistance. In addition to its telomere maintenance function,
      telomerase plays a pro-survival role, inducing decreased apoptosis and increased
      resistance against DNA damage. Elucidation of the molecular mechanisms underlying
      this effect is critical to improve treatment outcomes. Previously, our group
      showed higher telomerase reverse transcriptase(TERT) expression in cisplatin
      resistant osteosarcoma cells. In this study, confocal fluorescence microscopy
      experiments revealed that TERT translocates from the nucleus to mitochondria in
      cisplatin treated osteosarcoma cells. We observed decreased apoptosis rate and
      improved mitochondrial function in TERT-overexpressing cells following cisplatin
      treatment. Based on these results, we further established that TERT inhibits
      cisplatin-induced apoptosis independently of telomerase reverse transcriptase
      activity. Moreover, TERT suppressed cisplatin-induced apoptosis and improved
      mitochondrial function via alleviating intracellular ROS in osteosarcoma cells.
      Our finding that TERT shuttles from the nucleus to the mitochondrion in response
      to cisplatin treatment and inhibits cisplatin-induced apoptosis in osteosarcoma
      cells may be especially important to overcome drug resistance.

PMID- 28765566
TI  - Martian slope streaks as plausible indicators of transient water activity.
AB  - Slope streaks have been frequently observed in the equatorial, low thermal
      inertia and dusty regions of Mars. The reason behind their formation remains
      unclear with proposed hypotheses for both dry and wet mechanisms. Here, we report
      an up-to-date distribution and morphometric investigation of Martian slope
      streaks. We find: (i) a remarkable coexistence of the slope streak distribution
      with the regions on Mars with high abundances of water-equivalent hydrogen,
      chlorine, and iron; (ii) favourable thermodynamic conditions for transient
      deliquescence and brine development in the slope streak regions; (iii) a
      significant concurrence of slope streak distribution with the regions of enhanced
      atmospheric water vapour concentration, thus suggestive of a present-day regolith
      atmosphere water cycle; and (iv) terrain preferences and flow patterns supporting
      a wet mechanism for slope streaks. These results suggest a strong local regolith
      atmosphere water coupling in the slope streak regions that leads to the formation
      of these fluidised features. Our conclusions can have profound astrobiological,
      habitability, environmental, and planetary protection implications.

PMID- 28765567
TI  - Assessment of imprinting- and genetic variation-dependent monoallelic expression
      using reciprocal allele descendants between human family trios.
AB  - Genomic imprinting is an important epigenetic process that silences one of the
      parentally-inherited alleles of a gene and thereby exhibits allelic-specific
      expression (ASE). Detection of human imprinting events is hampered by the
      infeasibility of the reciprocal mating system in humans and the removal of ASE
      events arising from non-imprinting factors. Here, we describe a pipeline with the
      pattern of reciprocal allele descendants (RADs) through genotyping and
      transcriptome sequencing data across independent parent-offspring trios to
      discriminate between varied types of ASE (e.g., imprinting, genetic variation
      dependent ASE, and random monoallelic expression (RME)). We show that the vast
      majority of ASE events are due to sequence-dependent genetic variant, which are
      evolutionarily conserved and may themselves play a cis-regulatory role.
      Particularly, 74% of non-RAD ASE events, even though they exhibit ASE biases
      toward the same parentally-inherited allele across different individuals, are
      derived from genetic variation but not imprinting. We further show that the RME
      effect may affect the effectiveness of the population-based method for detecting
      imprinting events and our pipeline can help to distinguish between these two ASE
      types. Taken together, this study provides a good indicator for categorization of
      different types of ASE, opening up this widespread and complex mechanism for
      comprehensive characterization.

PMID- 28765568
TI  - Novel copy number variation of POMGNT1 associated with muscle-eye-brain disease
      detected by next-generation sequencing.
AB  - The protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) gene
      is one of 18 genes involved in the pathogenesis of alpha
      dystroglycanopathies(alpha-DGPs) such as muscle-eye-brain disease (MEB). Our
      study aimed to retrospectively analyze and characterize the clinical and genetic
      features of three MEB patients with POMGNT1 mutations. One female and two male
      patients from three unrelated families were diagnosed with MEB, manifesting
      hypotonia at birth, mental retardation, structural brain defects, and ocular
      malformations. The novel missense mutations c.296 T > C and c.794 G > C were
      revealed in patient 2 and patient 3 respectively by next-generation sequencing
      (NGS). Further NGS data analysis revealed that all three patients had the same
      novel copy number variations (CNV) g.6668-8257del, which was homozygous in
      patient 1 and heterozygous in patients 2 and 3. By long-range polymerase chain
      reaction (PCR) and Sanger sequencing, it was shown that the two breakpoints of
      the CNV localized to two AluY elements and displayed 42-bp of microhomology. The
      CNV was confirmed as a founder mutation by haplotype analysis. Our study
      indicated that NGS is a clinically useful method of detecting alpha-DGPs genes 
      related CNV, and the CNV is likely to be caused by Alu-Alu recombination or from
      a single ancestor bearing the deletion chromosome.

PMID- 28765569
TI  - Locus of Adhesion and Autoaggregation (LAA), a pathogenicity island present in
      emerging Shiga Toxin-producing Escherichia coli strains.
AB  - Shiga Toxin-producing Escherichia coli (STEC) are a group of foodborne pathogens
      associated with diarrhea, dysentery, hemorrhagic colitis (HC) and hemolytic
      uremic syndrome (HUS). Shiga toxins are the major virulence factor of these
      pathogens, however adhesion and colonization to the human intestine is required
      for STEC pathogenesis. A subset of STEC strains carry the Locus of Enterocyte
      Effacement (LEE) pathogenicity island (PAI), which encodes genes that mediate the
      colonization of the human intestine. While LEE-positive STEC strains have
      traditionally been associated with human disease, the burden of disease caused by
      STEC strains that lacks LEE (LEE-negative) has increased recently in several
      countries; however, in the absence of LEE, the molecular pathogenic mechanisms by
      STEC strains are unknown. Here we report a 86-kb mosaic PAI composed of four
      modules that encode 80 genes, including novel and known virulence factors
      associated with adherence and autoaggregation. Therefore, we named this PAI as
      Locus of Adhesion and Autoaggregation (LAA). Phylogenomic analysis using whole
      genome sequences of STEC strains available in the NCBI database indicates that
      LAA PAI is exclusively present in a subset of emerging LEE-negative STEC strains,
      including strains isolated from HC and HUS cases. We suggest that the acquisition
      of this PAI is a recent evolutionary event, which may contribute to the emergence
      of these STEC.

PMID- 28765570
TI  - Characterization and diversity of phages infecting Aeromonas salmonicida subsp.
      salmonicida.
AB  - Phages infecting Aeromonas salmonicida subsp. salmonicida, the causative agent of
      the fish disease furunculosis, have been isolated for decades but very few of
      them have been characterized. Here, the host range of 12 virulent phages,
      including three isolated in the present study, was evaluated against a panel of
      65 A. salmonicida isolates, including representatives of the psychrophilic
      subspecies salmonicida, smithia, masoucida, and the mesophilic subspecies
      pectinolytica. This bacterial set also included three isolates from India
      suspected of being members of a new subspecies. Our results allowed to elucidate
      a lytic dichotomy based on the lifestyle of A. salmonicida (mesophilic or
      psychrophilic) and more generally, on phage types (lysotypes) for the subspecies
      salmonicida. The genomic analyses of the 12 phages from this study with those
      available in GenBank led us to propose an A. salmonicida phage pan-virome. Our
      comparative genomic analyses also suggest that some phage genes were under
      positive selection and A. salmonicida phage genomes having a discrepancy in GC%
      compared to the host genome encode tRNA genes to likely overpass the bias in
      codon usage. Finally, we propose a new classification scheme for A. salmonicida
      phages.

PMID- 28765571
TI  - Thermal conductivity measurements of proton-heated warm dense aluminum.
AB  - Thermal conductivity is one of the most crucial physical properties of matter
      when it comes to understanding heat transport, hydrodynamic evolution, and energy
      balance in systems ranging from astrophysical objects to fusion plasmas. In the
      warm dense matter regime, experimental data are very scarce so that many
      theoretical models remain untested. Here we present the first thermal
      conductivity measurements of aluminum at 0.5-2.7 g/cc and 2-10 eV, using a
      recently developed platform of differential heating. A temperature gradient is
      induced in a Au/Al dual-layer target by proton heating, and subsequent heat flow
      from the hotter Au to the Al rear surface is detected by two simultaneous time
      resolved diagnostics. A systematic data set allows for constraining both thermal
      conductivity and equation-of-state models. Simulations using Purgatorio model or
      Sesame S27314 for Al thermal conductivity and LEOS for Au/Al release equation-of
      state show good agreement with data after 15 ps. Discrepancy still exists at
      early time 0-15 ps, likely due to non-equilibrium conditions.

PMID- 28765572
TI  - Association of handgrip strength with hospitalization, cardiovascular events, and
      mortality in Japanese patients with type 2 diabetes.
AB  - Handgrip strength is useful for the diagnosis of sarcopenia. We examined the
      associations of handgrip strength with all-cause mortality, cardiovascular
      events, and hospitalization in patients with type 2 diabetes. From April 2013 to
      December 2015, we conducted a retrospective cohort study to examine patients with
      type 2 diabetes whose handgrip strength was measured at our hospital. All
      patients were followed up until May 2016. A total of 1,282 patients (63.8 +/-
      13.9 years) were enrolled and followed up for 2.36 +/- 0.73 years. During the
      follow-up period, 20 patients (1.6%) died, 14 (1.1%) experienced cardiovascular
      events, and 556 (43.4%) were admitted to our hospital for any diseases. Multiple
      regression analyses revealed that handgrip strength was favorably associated with
      abdominal obesity and renal function. Moreover, Cox proportional hazard analyses
      with adjustment for potential confounding variables revealed that handgrip
      strength was significantly associated with occurrence of CVD events and
      hospitalization in all subjects. In addition, handgrip strength was significantly
      associated with mortality and hospitalization in men and with hospitalization in
      women. Handgrip strength could be a prognostic indicator for health as well as a
      diagnostic marker of skeletal muscle mass loss in Japanese patients with type 2
      diabetes.

PMID- 28765573
TI  - All-laser-micromachining of ridge waveguides in LiNbO3 crystal for mid-infrared
      band applications.
AB  - The femtosecond laser micromachining of transparent optical materials offers a
      powerful and feasible solution to fabricate versatile photonic components towards
      diverse applications. In this work, we report on a new design and fabrication of
      ridge waveguides in LiNbO3 crystal operating at the mid-infrared (MIR) band by
      all-femtosecond-laser microfabrication. The ridges consist of laser-ablated
      sidewalls and laser-written bottom low-index cladding tracks, which are
      constructed for horizontal and longitudinal light confinement, respectively. The
      ridge waveguides are found to support good guidance at wavelength of 4 MUm. By
      applying this configuration, Y-branch waveguiding structures (1 * 2 beam
      splitters) have been produced, which reach splitting ratios of ~1:1 at 4 MUm.
      This work paves a simple and feasible way to construct novel ridge waveguide
      devices in dielectrics through all-femtosecond-laser micro-processing.

PMID- 28765574
TI  - The East Asian summer monsoon variability over the last 145 years inferred from
      the Shihua Cave record, North China.
AB  - The precipitation variability associated with the East Asian summer monsoon
      (EASM) has profound societal implications. Here, we use precisely dated and
      seasonally-resolved stalagmite oxygen isotope (delta18O) records from Shihua
      Cave, North China to reconstruct the EASM variability over the last 145 years.
      Our record shows a remarkable weakening of the EASM strength since the 1880s,
      which may be causally linked to the warming of the tropical Pacific and Indian
      Oceans. The delta18O record also exhibits a significant ~30-year periodicity,
      consistent with the instrumental, historical and proxy-based rainfall records
      from North China, plausibly driven by the Pacific Decadal Oscillation (PDO).
      Together, these observations imply that ~30-year periodicity is a persistent
      feature of the EASM, which remains significant with or without anthropogenic
      forcing. If indeed, the EASM rainfall in North China might decline significantly
      in the near future, which may affect millions of people in this region.

PMID- 28765575
TI  - Spontaneous breaking of time-reversal symmetry in topological superconductors.
AB  - We study the behavior of spinless fermions in superconducting state, in which the
      phases of the superconducting order parameter depend on the direction of the
      link. We find that the energy of the superconductor depends on the phase
      differences of the superconducting order parameter. The solutions for the phases
      corresponding to the energy minimuma, lead to a topological superconducting state
      with the nontrivial Chern numbers. We focus our quantitative analysis on the
      properties of topological states of superconductors with different crystalline
      symmetry and show that the phase transition in the topological superconducting
      state is result of spontaneous breaking of time-reversal symmetry in the
      superconducting state. The peculiarities in the chiral gapless edge modes
      behavior are studied, the Chern numbers are calculated.

PMID- 28765576
TI  - Visualization of Synthetic Vascular Smooth Muscle Cells in Atherosclerotic
      Carotid Rat Arteries by F-18 FDG PET.
AB  - Synthetic vascular smooth muscle cells (VSMCs) play important roles in
      atherosclerosis, in-stent restenosis, and transplant vasculopathy. We
      investigated the synthetic activity of VSMCs in the atherosclerotic carotid
      artery using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET).
      Atherosclerosis was induced in rats by partial ligation of the right carotid
      artery coupled with an atherogenic diet and vitamin D injections (2 consecutive
      days, 600,000 IU/day). One month later, rats were imaged by F-18 FDG PET. The
      atherosclerotic right carotid arteries showed prominent luminal narrowing with
      neointimal hyperplasia. The regions with neointimal hyperplasia were composed of
      alpha-smooth muscle actin-positive cells with decreased expression of smooth
      muscle myosin heavy chain. Surrogate markers of synthetic VSMCs such as collagen
      type III, cyclophilin A, and matrix metallopeptidase-9 were increased in
      neointima region. However, neither macrophages nor neutrophils were observed in
      regions with neointimal hyperplasia. F-18 FDG PET imaging and autoradiography
      showed elevated FDG uptake into the atherosclerotic carotid artery. The inner
      vessel layer showed higher tracer uptake than the outer layer. Consistently, the
      expression of glucose transporter 1 was highly increased in neointima. The
      present results indicate that F-18 FDG PET may be a useful tool for evaluating
      synthetic activities of VSMCs in vascular remodeling disorders.

PMID- 28765577
TI  - CACNA1C polymorphisms Impact Cognitive Recovery in Patients with Bipolar Disorder
      in a Six-week Open-label Trial.
AB  - Cognitive impairments in bipolar patients deteriorate as the disorder progresses.
      Little is known about whether genetic risks impact cognitive recovery during the
      course from depression to remission. In this six-week open-label trial, we shed
      light on the impacts of six single nucleotide polymorphisms (SNPs) in the calcium
      voltage-gated channel subunit alpha1 C (CACNA1C) gene on cognitive recovery in
      192 bipolar patients suffering a major depressive episode (MDE). The primary
      outcome measures were changes in a battery of neuropsychological tests following
      6-week treatment. Carriers with rs10466907 GT genotype did not significantly
      improve their executive function total scores on the Wisconsin Card Sorting Test
      after six weeks of treatment compared to the TT genotypes (beta = -0.944, 95%
      Confidence Interval (CI) = -1.482--0.405). Moreover, during a MDE carriers with
      rs58619945 GG and GA genotypes performed significantly worse than those with AA
      genotype on the categories completed (p = 0.013 and p = 0.001), total errors (p =
      0.039 and p = 0.009), and random errors (p = 0.055 and p = 0.014, respectively).
      Our data suggest that the tested CACNA1C SNPs may have impacts on cognitive
      recovery from depression.

PMID- 28765578
TI  - Selection of reference genes for expression analysis using RT-qPCR in the
      dissemination system of Heliothis virescens ascovirus 3 h (HvAV-3h).
AB  - Ascoviruses are double-stranded DNA viruses that mainly infect noctuid larvae,
      and are transmitted by the parasitoid wasp Microplitis similis Lyle. Ascovirus
      parasitoids wasp-noctuid insects constitute the dissemination system. Selection
      of suitable reference genes for the dissemination system could play an important
      role in elucidating the pathogenic molecular mechanisms of ascovirus.
      Unfortunately, such studies on potential reference genes in the dissemination
      system of ascoviruses are lacking. In the present study, we evaluated 11
      candidate reference genes: beta-actin1 (ACT1), beta-actin2 (ACT2), elongation
      factor 1 (EF1), elongation factor 2 (EF2), ribosomal protein L10 (L10), ribosomal
      protein L17A (L17A), superoxide dismutase (SOD), 28S ribosome (28S), Tubulin
      (TUB) and 18S ribosome (18S). The samples were originally from various virus
      concentrations and points-in-time of experimental treatments using RefFinder and
      four algorithms. The results showed that EF1 was the most stable internal gene in
      S. exigua and M. similis and that EF2 was the most stable in the IOZCAS-Spex-II-A
      cell line, and the stability of reference genes were confirmed via the expression
      levels of two inhibitor of apoptosis-like (iap-like) genes from Heliothis
      virescens ascovirus 3 h (HvAV-3h). This study provides a crucial basis for future
      research that explores the molecular mechanisms of the pathogenesis of
      ascoviruses.

PMID- 28765580
TI  - Quantifying Crustal Thickness in Continental Collisional Belts: Global
      Perspective and a Geologic Application.
AB  - We present compiled geochemical data of young (mostly Pliocene-present)
      intermediate magmatic rocks from continental collisional belts and correlations
      between their whole-rock Sr/Y and La/Yb ratios and modern crustal thickness.
      These correlations, which are similar to those obtained from subduction-related
      magmatic arcs, confirm that geochemistry can be used to track changes of crustal
      thickness changes in ancient collisional belts. Using these results, we
      investigate temporal variations of crustal thickness in the Qinling Orogenic Belt
      in mainland China. Our results suggest that crustal thickness remained constant
      in the North Qinling Belt (~45-55 km) during the Triassic to Jurassic but
      fluctuates in the South Qinling Belt, corresponding to independently determined
      tectonic changes. In the South Qinling Belt, crustal thickening began at ~240 Ma
      and culminated with 60-70-km-thick crust at ~215 Ma. Then crustal thickness
      decreased to ~45 km at ~200 Ma and remained the same to the present. We propose
      that coupled use of Sr/Y and La/Yb is a feasible method for reconstructing
      crustal thickness through time in continental collisional belts. The combination
      of the empirical relationship in this study with that from subduction-related
      arcs can provide the crustal thickness evolution of an orogen from oceanic
      subduction to continental collision.

PMID- 28765579
TI  - Inhibition of AKT1 signaling promotes invasion and metastasis of non-small cell
      lung cancer cells with K-RAS or EGFR mutations.
AB  - Accumulating evidence supports a role of the PI3K-AKT pathway in the regulation
      of cell motility, invasion and metastasis. AKT activation is known to promote
      metastasis, however under certain circumstances, it also shows an inhibitory
      activity on metastatic processes, and the cause of such conflicting results is
      largely unclear. Here we found that AKT1 is an important regulator of metastasis
      and down-regulation of its activity is associated with increased metastatic
      potential of A549 cells. Inhibition of AKT1 enhanced migration and invasion in
      KRAS- or EGFR-mutant non-small cell lung cancer (NSCLC) cells. The allosteric AKT
      inhibitor MK-2206 promoted metastasis of KRAS-mutated A549 cells in vivo. We next
      identified that the phosphorylation of Myristoylated alanine-rich C-kinase
      substrate (MARCKS) and LAMC2 protein level were increased with AKT1 inhibition,
      and MARCKS or LAMC2 knockdown abrogated migration and invasion induced by AKT1
      inhibition. This study unravels an anti-metastatic role of AKT1 in the NSCLC
      cells with KRAS or EGFR mutations, and establishes an AKT1-MARCKS-LAMC2 feedback
      loop in this regulation.

PMID- 28765582
TI  - Pancreatic cancer: Biomarkers for the early detection of PDAC.

PMID- 28765583
TI  - Liver cancer: Translating '-omics' results into precision medicine for
      hepatocellular carcinoma.

PMID- 28765581
TI  - Oropharyngeal mucosal transmission of Zika virus in rhesus macaques.
AB  - Zika virus is present in urine, saliva, tears, and breast milk, but the
      transmission risk associated with these body fluids is currently unknown. Here we
      evaluate the risk of Zika virus transmission through mucosal contact in rhesus
      macaques. Application of high-dose Zika virus directly to the tonsils of three
      rhesus macaques results in detectable plasma viremia in all animals by 2 days
      post-exposure; virus replication kinetics are similar to those observed in
      animals infected subcutaneously. Three additional macaques inoculated
      subcutaneously with Zika virus served as saliva donors to assess the transmission
      risk from contact with oral secretions from an infected individual. Seven naive
      animals repeatedly exposed to donor saliva via the conjunctivae, tonsils, or
      nostrils did not become infected. Our results suggest that there is a risk of
      Zika virus transmission via the mucosal route, but that the risk posed by oral
      secretions from individuals with a typical course of Zika virus infection is
      low.Zika virus (ZIKV) is present in body fluids, including saliva, but
      transmission risk through mucosal contact is not well known. Here, the authors
      show that oropharyngeal mucosal infection of macaques with a high ZIKV dose
      results in viremia, but that transmission risk from saliva of infected animals is
      low.

PMID- 28765584
TI  - Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by
      Inhibition of Notch Signaling.
AB  - Oleanolic acid (OA), a pentacyclic triterpenoid, has been shown to modulate
      multiple signaling pathways in a variety of cell linages. But the mechanisms
      underlying OA-mediated mesenchymal stromal cell (MSC) osteogenic differentiation
      are not known. In this study, we examined effects of OA on cell viability,
      osteogenic differentiation in MSCs, and the involvement of Notch and BMP
      signaling. OA induced bone marrow derived MSC differentiation towards
      osteoprogenitor cells and inhibited Notch signaling in a dose dependent manner.
      Constitutive activation of Notch signaling fully blocked OA induced MSC
      osteogenic differentiation. The expression level of early osteogenic marker
      genes, ALP, Runx2, and type I collagen, which play a critical role in MSC to
      osteoblast transition and servers as a downstream target of BMP signaling, was
      significantly induced by OA. Furthermore, BMP2 mediated MSC osteogenic
      differentiation was significantly enhance by OA treatment, indicating a
      synergistic effect between BMP2 and OA. Our results suggest that OA is a
      promising bioactive agent for bone tissue regeneration, and inhibition of Notch
      signaling is required for its osteogenic effects on MSCs.

PMID- 28765585
TI  - Multi-color single-molecule tracking and subtrajectory analysis for
      quantification of spatiotemporal dynamics and kinetics upon T cell activation.
AB  - The dynamic properties of molecules in living cells are attracting increasing
      interest. We propose a new method, moving subtrajectory analysis using single
      molecule tracking, and demonstrate its utility in the spatiotemporal
      quantification of not only dynamics but also the kinetics of interactions using
      single-color images. Combining this technique with three-color simultaneous
      single-molecule imaging, we quantified the dynamics and kinetics of molecules in
      spatial relation to T cell receptor (TCR) microclusters, which trigger TCR
      signaling. CD3epsilon, a component of the TCR/CD3 complex, and CD45, a
      phosphatase positively and negatively regulating signaling, were each found in
      two mobility states: faster (associated) and slower (dissociated) states.
      Dynamics analysis suggests that the microclusters are loosely composed of
      heterogeneous nanoregions, possibly surrounded by a weak barrier. Kinetics
      analysis quantified the association and dissociation rates of interactions with
      the microclusters. The associations of both CD3epsilon and CD45 were single-step
      processes. In contrast, their dissociations were each composed of two components,
      indicating transient and stable associated states. Inside the microclusters, the
      association was accelerated, and the stable association was increased. Only CD45
      showed acceleration of association at the microcluster boundary, suggesting
      specific affinity on the boundary. Thus, this method is an innovative and
      versatile tool for spatiotemporal quantification.

PMID- 28765586
TI  - Improving Urban Stormwater Runoff Quality by Nutrient Removal through Floating
      Treatment Wetlands and Vegetation Harvest.
AB  - Two floating treatment wetlands (FTWs) in experimental tanks were compared in
      terms of their effectiveness on removing nutrients. The results showed that the
      FTWs were dominated by emergent wetland plants and were constructed to remove
      nutrients from simulated urban stormwater. Iris pseudacorus and Thalia dealbata
      wetland systems were effective in reducing the nutrient. T. dealbata FTWs showed
      higher nutrient removal performance than I. pseudacorus FTWs. Nitrogen (N) and
      phosphorous (P) removal rates in water by T. dealbata FTWs were 3.95 +/- 0.19 and
      0.15 +/- 0.01 g/m2/day, respectively. For I. pseudacorus FTWs, the TN and TP
      removal rates were 3.07 +/- 0.15 and 0.14 +/- 0.01 g/m2/day, respectively. The
      maximum absolute growth rate for T. dealbata corresponded directly with the
      maximum mean nutrient removal efficiency during the 5th stage. At harvest, N and
      P uptak of T. dealbata was 23.354 +/- 1.366 g and 1.489 +/- 0.077 g per plant,
      respectively, approximate twice as high as by I. pseudacorus.

PMID- 28765587
TI  - Theoretical isotopic fractionation of magnesium between chlorophylls.
AB  - Magnesium is the metal at the center of all types of chlorophyll and is thus
      crucial to photosynthesis. When an element is involved in a biosynthetic pathway
      its isotopes are fractionated based on the difference of vibrational frequency
      between the different molecules. With the technical advance of multi-collectors
      plasma-mass-spectrometry and improvement in analytical precision, it has recently
      been found that two types of chlorophylls (a and b) are isotopically distinct.
      These results have very significant implications with regards to the use of Mg
      isotopes to understand the biosynthesis of chlorophyll. Here we present
      theoretical constraints on the origin of these isotopic fractionations through ab
      initio calculations. We present the fractionation factor for chlorphyll a, b, d,
      and f. We show that the natural isotopic variations among chlorophyll a and b are
      well explained by isotopic fractionation under equilibrium, which implies
      exchanges of Mg during the chlorophyll cycle. We predict that chlorophyll d and f
      should be isotopically fractionated compared to chlorophyll a and that this could
      be used in the future to understand the biosynthesis of these molecules.

PMID- 28765588
TI  - Rakicidin F, a new antibacterial cyclic depsipeptide from a marine sponge-derived
      Streptomyces sp.
AB  - A new cyclic depsipeptide, rakicidin F (1), along with the known compound
      rakicidin C (2), was isolated from the fermentation broth of the marine sponge
      derived actinomycete strain Streptomyces sp. GKU 220. Their structures were
      elucidated by interpreting the HRFABMS and NMR spectroscopic data. Rakicidin F
      (1) showed growth inhibitory activity against bacteria.The Journal of Antibiotics
      advance online publication, 2 August 2017; doi:10.1038/ja.2017.92.

PMID- 28765589
TI  - Comparing the action of HT61 and chlorhexidine on natural and model
      Staphylococcus aureus membranes.
AB  - HT61 and chlorhexidine (CHX) are both putative membrane-active antimicrobials,
      which non-specifically target the anionic lipids abundant in bacterial membranes.
      In model systems, the ability of these antimicrobials to partition into lipid
      monolayers and increase the permeability of lipid bilayers is dependent upon the
      presence and proportion of anionic lipids such as phosphatidylglycerol. Despite
      their apparent similarity in membrane affinity, we have found that HT61 and CHX
      differ in the extent to which they affect membrane integrity. HT61 was found to
      be capable of severely disrupting the lipid bilayer, resulting in lysis of
      Staphylococcus aureus membranes and the release of ATP from protoplasts. CHX, by
      contrast, does not disrupt the lipid bilayer to a sufficiently large degree to
      result in lysis of the membrane or release of ATP from S. aureus protoplasts.
      This suggests that although antimicrobials that interact with the membrane often
      have a common target, the action they have on the membrane may differ widely and
      may not be the primary mode of action of the antimicrobial.

PMID- 28765590
TI  - Formal synthesis of englerin A utilizing regio- and diastereoselective [4+3]
      cycloaddition.
AB  - Englerin A, a guaiane sesquiterpene isolated from Phyllanthus engleri, showed
      highly potent and selective growth inhibitory activities against renal cancer
      cell lines. We synthesized the key tricyclic intermediate from commercially
      available 2,2-dimethyl-1,3-dioxan-5-one via regio- and diastereoselective [4+3]
      cycloaddition between the formyl enol silyl ether and the disubstituted furan, in
      4.8% total yield over 10 steps.

PMID- 28765591
TI  - HPV prevalence in the foreskins of asymptomatic healthy infants and children:
      Systematic review and meta-analysis.
AB  - The true HPV prevalence in the foreskins of infants and children has been little
      documented, but reporting on this prevalence is of great importance given its
      impact on the rationale for treating asymptomatic boys. We searched multiple
      databases from 1960 to 2016 for observational or prospective studies that
      reported on HPV prevalence in foreskins. We conducted a meta-analysis using a
      random-effects model to pool for HPV prevalence in the foreskins of infants and
      children. Eight studies, with a total of 556 infants and children with phimosis,
      were eligible for the meta-analysis. The pooled overall prevalence of general
      HPV, high-risk HPV, low-risk HPV, HPV 16/18, HPV 16, and HPV 18 were 17.3 (95%CI:
      0.8-46.3), 12.1 (95% CI: 0.9-31.5), 2.4 (95% CI: 0.0-11.2), 4.8 (95% CI: 0.0
      16.8), 1.7 (95% CI: 0.0-5.1), and 0 (95% CI: 0-0.5), respectively. The estimated
      HPV prevalence in foreskins was not zero among infants and children, which
      implies HPV transmission other than by sexual contact. Considering that high-risk
      HPV is detected in asymptomatic infants and children, future studies are
      warranted to determine whether preventive treatments in asymptomatic infants and
      children could be effective in preventing persistence or transmission of high
      risk HPV.

PMID- 28765592
TI  - Fabrication of Epitaxial Fe3O4 Film on a Si(111) Substrate.
AB  - The application of magnetic oxides in spintronics has recently attracted much
      attention. The epitaxial growth of magnetic oxide on Si could be the first step
      of new functional spintronics devices with semiconductors. However, epitaxial
      spinel ferrite films are generally grown on oxide substrates, not on
      semiconductors. To combine oxide spintronics and semiconductor technology, we
      fabricated Fe3O4 films through epitaxial growth on a Si(111) substrate by
      inserting a gamma-Al2O3 buffer layer. Both of gamma-Al2O3 and Fe3O4 layer grew
      epitaxially on Si and the films exhibited the magnetic and electronic properties
      as same as bulk. Furthermore, we also found the buffer layer dependence of
      crystal structure of Fe3O4 by X-ray diffraction and high-resolution transmission
      electron microscope. The Fe3O4 films on an amorphous-Al2O3 buffer layer grown at
      room temperature grew uniaxially in the (111) orientation and had a textured
      structure in the plane. When Fe3O4 was deposited on Si(111) directly, the poly
      crystal Fe3O4 films were obtained due to SiOx on Si substrate. The epitaxial
      Fe3O4 layer on Si substrates enable us the integration of highly functional
      spintoronic devices with Si technology.

PMID- 28765593
TI  - Folding driven self-assembly of a stimuli-responsive peptide-hyaluronan hybrid
      hydrogel.
AB  - Protein-metal ion interactions are ubiquitous in nature and can be utilized for
      controlling the self-assembly of complex supramolecular architectures and
      materials. Here, a tunable supramolecular hydrogel is described, obtained by self
      assembly of a Zn2+-responsive peptide-hyaluronic acid hybrid synthesized using
      strain promoted click chemistry. Addition of Zn2+ triggers folding of the
      peptides into a helix-loop-helix motif and dimerization into four-helix bundles,
      resulting in hydrogelation. Removal of the Zn2+ by chelators results in rapid
      hydrogel disassembly. Degradation of the hydrogels can also be time-programed by
      encapsulation of a hydrolyzing enzyme within the gel, offering multiple
      possibilities for modulating materials properties and release of encapsulated
      species. The hydrogel further shows potential antioxidant properties when
      evaluated using an in vitro model for reactive oxygen species.

PMID- 28765594
TI  - Evaluation of realistic layouts for next generation on-scalp MEG: spatial
      information density maps.
AB  - While commercial magnetoencephalography (MEG) systems are the functional
      neuroimaging state-of-the-art in terms of spatio-temporal resolution, MEG sensors
      have not changed significantly since the 1990s. Interest in newer sensors that
      operate at less extreme temperatures, e.g., high critical temperature (high-T c)
      SQUIDs, optically-pumped magnetometers, etc., is growing because they enable
      significant reductions in head-to-sensor standoff (on-scalp MEG). Various metrics
      quantify the advantages of on-scalp MEG, but a single straightforward one is
      lacking. Previous works have furthermore been limited to arbitrary and/or
      unrealistic sensor layouts. We introduce spatial information density (SID) maps
      for quantitative and qualitative evaluations of sensor arrays. SID-maps present
      the spatial distribution of information a sensor array extracts from a source
      space while accounting for relevant source and sensor parameters. We use it in a
      systematic comparison of three practical on-scalp MEG sensor array layouts (based
      on high-T c SQUIDs) and the standard Elekta Neuromag TRIUX magnetometer array.
      Results strengthen the case for on-scalp and specifically high-T c SQUID-based
      MEG while providing a path for the practical design of future MEG systems. SID
      maps are furthermore general to arbitrary magnetic sensor technologies and source
      spaces and can thus be used for design and evaluation of sensor arrays for
      magnetocardiography, magnetic particle imaging, etc.

PMID- 28765596
TI  - A polymorphism in ABCC4 is related to efficacy of 5-FU/capecitabine-based
      chemotherapy in colorectal cancer patients.
AB  - To investigate the association of microRNA (miRNA) binding-site polymorphisms in
      the drug transporter genes with the efficacy of 5-Fluorouracil (5
      FU)/capecitabine-based chemotherapy in colorectal cancer (CRC), 6 polymorphisms
      were determined in 432 CRC patients by using DNA sequencing method. The impacts
      of the polymorphisms on the miRNA-mediated regulation of gene expression were
      evaluated by using the methods including quantitative real-time PCR, western
      blotting, and luciferase reporter assays. The effects of miRNA on the
      intracellular concentration and cytotoxicity of 5-FU in CRC cells were measured
      by high performance liquid chromatography conjected tandem mass spectrometry
      (HPLC-MS/MS) and MTT methods, respectively. Statistical analysis showed that a
      polymorphism rs3742106 in the 3'-UTR of ATP-binding cassette subfamily C member 4
      (ABCC4) gene was significantly associated with the efficacy of 5-FU/capecitabine
      based chemotherapy in CRC. The patients with T/T genotype had significantly
      higher response rate than those with G/G and G/T genotypes. The expression of
      ABCC4 was inhibited by miR-3190-5p through binding to the 3'-UTR of the ABCC4
      gene. This regulatory role of miR-3190-5p was disrupted by rs3742106.
      Furthermore, we found that the intracellular concentration of 5-FU was elevated
      by miR-3190-5p, and consequently the sensitivity of CRC cells to 5-FU was also
      enhanced. Rs3742106 might be regarded as a genetic biomarker for individualized
      use of 5-FU and capecitabine in CRC.

PMID- 28765595
TI  - Integration of miRNA and mRNA expression profiles reveals microRNA-regulated
      networks during muscle wasting in cardiac cachexia.
AB  - Cardiac cachexia (CC) is a common complication of heart failure (HF) associated
      with muscle wasting and poor patient prognosis. Although different mechanisms
      have been proposed to explain muscle wasting during CC, its pathogenesis is still
      not understood. Here, we described an integrative analysis between miRNA and mRNA
      expression profiles of muscle wasting during CC. Global gene expression profiling
      identified 1,281 genes and 19 miRNAs differentially expressed in muscle wasting
      during CC. Several of these deregulated genes are known or putative targets of
      the altered miRNAs, including miR-29a-3p, miR-29b-3p, miR-210-5p, miR-214, and
      miR-489. Gene ontology analysis on integrative mRNA/miRNA expression profiling
      data revealed miRNA interactions affecting genes that regulate extra-cellular
      matrix (ECM) organization, proteasome protein degradation, citric acid cycle and
      respiratory electron transport. We further identified 11 miRNAs, including miR
      29a-3p and miR-29b-3p, which target 21 transcripts encoding the collagen proteins
      related to ECM organization. Integrative miRNA and mRNA global expression data
      allowed us to identify miRNA target genes involved in skeletal muscle wasting in
      CC. Our functional experiments in C2C12 cells confirmed that miR-29b down
      regulates collagen genes and contributes to muscle cell atrophy. Collectively,
      our results suggest that key ECM-associated miRNAs and their target genes may
      contribute to CC in HF.

PMID- 28765597
TI  - Greenhouse gas emissions as a result of spectators travelling to football in
      England.
AB  - Transport remains a critical avenue in the attempt to reduce greenhouse gas (GHG)
      emissions and any significant effort to reduce travel GHG emissions will need to
      encourage a movement towards more fuel-efficient, less polluting behaviours. The
      aim of this paper is to calculate GHG emissions arising from the travel of
      spectators to and from football games within eight football tiers (3 to 10) in
      England, and to extrapolate this to a national level. The study comprised of 1649
      participants with an average age of 42 years (M = 42.63, SD = 17.10).
      Participants travelled to and from games by walking, cycling, car, bus, train or
      taxi. The average distance travelled to and from games was 41.5 km. A Kruskal
      Wallis test was conducted to evaluate differences in travel related GHG emissions
      between the eight football tiers during the 2012/13 season. The results indicate
      significant differences between football tiers' GHG emissions, H(7) = 46.474, p <
      0.001. The annual GHG emission of spectators from the 8 tiers for the 2012/13
      season was estimated at 56,237 tonnes of CO2e, accounting for less than 0.05% of
      transport emissions in England. Football authorities should have robust travel
      plans and educate spectators to employ more sustainable travel plans to games.

PMID- 28765598
TI  - Synthesis and Multi Scale Tribological Behavior of WC-Co/Nanodiamond
      Nanocomposites.
AB  - Nanodiamonds (ND) present a unique combination of desirable mechanical,
      functional, and chemical characteristics that are ideally suited for reinforcing
      and enhancing the wear resistance of carbide based materials. Tungsten carbide
      cobalt (WC-Co) matrix nanocomposites reinforced with varying amounts of ND (2 -
      10 vol.%) were synthesized here by spark plasma sintering. The rapid thermal
      consolidation route enabled attainment of dense samples with a significant
      retention of the metastable diamond phase. NDs affected the microstructural
      evolution, chemistry, and mechanical properties of WC-Co. Macroscale
      reciprocating pin-on-disk tests were conducted to assess wear behavior under
      conditions relevant to service environments, e.g., high cycles and high contact
      pressure. Microscale tribological properties were assessed using microscratch
      tests in order to investigate the intrinsic effects of ND on the localized
      mechanical and tribological response of WC-Co-ND composites. The incorporation of
      10 vol.% ND enhanced wear resistance at both the micro- and macroscale, by 28%
      and 35%, respectively.

PMID- 28765599
TI  - Metal-Insulator Transition in Nanoparticle Solids: Insights from Kinetic Monte
      Carlo Simulations.
AB  - Progress has been rapid in increasing the efficiency of energy conversion in
      nanoparticles. However, extraction of the photo-generated charge carriers remains
      challenging. Encouragingly, the charge mobility has been improved recently by
      driving nanoparticle (NP) films across the metal-insulator transition (MIT). To
      simulate MIT in NP films, we developed a hierarchical Kinetic Monte Carlo
      transport model. Electrons transfer between neighboring NPs via activated hopping
      when the NP energies differ by more than an overlap energy, but transfer by a non
      activated quantum delocalization, if the NP energies are closer than the overlap
      energy. As the overlap energy increases, emerging percolating clusters support a
      metallic transport across the entire film. We simulated the evolution of the
      temperature-dependent electron mobility. We analyzed our data in terms of two
      candidate models of the MIT: (a) as a Quantum Critical Transition, signaled by an
      effective gap going to zero; and (b) as a Quantum Percolation Transition, where a
      sample-spanning metallic percolation path is formed as the fraction of the
      hopping bonds in the transport paths is going to zero. We found that the Quantum
      Percolation Transition theory provides a better description of the MIT. We also
      observed an anomalously low gap region next to the MIT. We discuss the relevance
      of our results in the light of recent experimental measurements.

PMID- 28765600
TI  - Combinatorial metabolic engineering of Pseudomonas putida KT2440 for efficient
      mineralization of 1,2,3-trichloropropane.
AB  - An industrial waste, 1,2,3-trichloropropane (TCP), is toxic and extremely
      recalcitrant to biodegradation. To date, no natural TCP degraders able to
      mineralize TCP aerobically have been isolated. In this work, we engineered a
      biosafety Pseudomonas putida strain KT2440 for aerobic mineralization of TCP by
      implantation of a synthetic biodegradation pathway into the chromosome and
      further improved TCP mineralization using combinatorial engineering strategies.
      Initially, a synthetic pathway composed of haloalkane dehalogenase, haloalcohol
      dehalogenase and epoxide hydrolase was functionally assembled for the conversion
      of TCP into glycerol in P. putida KT2440. Then, the growth lag-phase of using
      glycerol as a growth precursor was eliminated by deleting the glpR gene,
      significantly enhancing the flux of carbon through the pathway. Subsequently, we
      improved the oxygen sequestering capacity of this strain through the heterologous
      expression of Vitreoscilla hemoglobin, which makes this strain able to mineralize
      TCP under oxygen-limited conditions. Lastly, we further improved intracellular
      energy charge (ATP/ADP ratio) and reducing power (NADPH/NADP+ ratio) by deleting
      flagella-related genes in the genome of P. putida KT2440. The resulting strain
      (named KTU-TGVF) could efficiently utilize TCP as the sole source of carbon for
      growth. Degradation studies in a bioreactor highlight the value of this
      engineered strain for TCP bioremediation.

PMID- 28765601
TI  - Enhanced robustness of evolving open systems by the bidirectionality of
      interactions between elements.
AB  - Living organisms, ecosystems, and social systems are examples of complex systems
      in which robustness against inclusion of new elements is an essential feature. A
      recently proposed simple model has revealed a general mechanism by which such
      systems can become robust against inclusion of elements with totally random
      interactions when the elements have a moderate number of links. The interaction
      is, however, in many systems often intrinsically bidirectional like for mutual
      symbiosis and competition in ecology. This study reports the strong reinforcement
      effect of the bidirectionality of the interactions on the robustness of evolving
      systems. We show that the system with purely bidirectional interactions can grow
      with twofold average degree, in comparison with the purely unidirectional system.
      This drastic shift of the transition point comes from the reinforcement of each
      node, not from a change in structure of the emergent system. For systems with
      partially bidirectional interactions we find that the regime of the growing phase
      gets expanded. In the dense interaction regime, there exists an optimum
      proportion of bidirectional interactions for the growth rate at around 1/3. In
      the sparsely connected systems, small but finite fraction of bidirectional links
      can change the system's behaviour from non-growing to growing.

PMID- 28765602
TI  - ARC is essential for maintaining pancreatic islet structure and beta-cell
      viability during type 2 diabetes.
AB  - Pancreatic beta-cell loss through apoptosis is an important disease mechanism in
      type 2 diabetes. Apoptosis Repressor with CARD (ARC) is a cell death inhibitor
      that antagonizes multiple death programs. We previously reported that ARC is
      abundant in pancreatic beta-cells and modulates survival of these cells in vitro.
      Herein we assessed the importance of endogenous ARC in maintaining islet
      structure and function in vivo. While generalized loss of ARC did not result in
      detectable abnormalities, its absence in ob/ob mice, a model of type 2 diabetes,
      induced a striking pancreatic phenotype: marked beta-cell death, loss of beta
      cell mass, derangements of islet architecture, and impaired glucose-stimulated
      insulin secretion in vivo. These abnormalities contributed to worsening of
      hyperglycemia and glucose-intolerance in these mice. Mechanistically, the absence
      of ARC increased levels of C/EBP homologous protein (CHOP) in wild type isolated
      islets stimulated with ER stress and in ob/ob isolated islets at baseline.
      Deletion of CHOP in ob/ob; ARC -/- mice led to reversal of beta-cell death and
      abnormalities in islet architecture. These data indicate that suppression of CHOP
      by endogenous levels of ARC is critical for beta-cell viability and maintenance
      of normal islet structure in this model of type 2 diabetes.

PMID- 28765604
TI  - A facile method of transforming FGD gypsum to alpha-CaSO4.0.5H2O whiskers with
      cetyltrimethylammonium bromide (CTAB) and KCl in glycerol-water solution.
AB  - A facile method to transform flue gas desulfurization gypsum (FGD gypsum) to
      alpha- calcium sulfate hemihydrate (alpha-HH) whiskers with high aspect ratios
      mediated by cetyltrimethylammonium bromide (CTAB) and KCl in glycerol-water
      solutions was studied. Addition of KCl facilitated the dissolution of calcium
      sulfate dihydrate (DH) and created a much higher supersaturation, which could
      come into being a larger driving force for the phase transformation from DH to
      alpha-HH. CTAB as the crystal modifier can significantly promoted 1-D growth of
      alpha-HH whiskers along the c axis and the presence of 0.25% CTAB (by weight of
      FGD gypsum) resulted in the increase of the average aspect ratio of alpha-HH
      whiskers from 28.9 to 188.4, which might be attributed to the preferential
      adsorption of C16H33(CH3)3N+ on the negative side facets of alpha-HH crystal.

PMID- 28765603
TI  - Predictions of Backbone Dynamics in Intrinsically Disordered Proteins Using De
      Novo Fragment-Based Protein Structure Predictions.
AB  - Intrinsically disordaered proteins (IDPs) are a prevalent phenomenon with over
      30% of human proteins estimated to have long disordered regions. Computational
      methods are widely used to study IDPs, however, nearly all treat disorder in a
      binary fashion, not accounting for the structural heterogeneity present in
      disordered regions. Here, we present a new de novo method, FRAGFOLD-IDP, which
      addresses this problem. Using 200 protein structural ensembles derived from NMR,
      we show that FRAGFOLD-IDP achieves superior results compared to methods which can
      predict related data (NMR order parameter, or crystallographic B-factor).
      FRAGFOLD-IDP produces very good predictions for 33.5% of cases and helps to get a
      better insight into the dynamics of the disordered ensembles. The results also
      show it is not necessary to predict the correct fold of the protein to reliably
      predict per-residue fluctuations. It implies that disorder is a local property
      and it does not depend on the fold. Our results are orthogonal to DynaMine, the
      only other method significantly better than the naive prediction. We therefore
      combine these two using a neural network. FRAGFOLD-IDP enables better insight
      into backbone dynamics in IDPs and opens exciting possibilities for the design of
      disordered ensembles, disorder-to-order transitions, or design for protein
      dynamics.

PMID- 28765605
TI  - The potential of using semitendinosus tendon as autograft in rabbit meniscus
      reconstruction.
AB  - Since transplantation of meniscal allograft or artificial menisci is limited by
      graft sources and a series of adverse events, substitution for meniscus
      reconstruction still needs to be explored. Natural biomaterials, which can
      provide a unique 3-D microenvironment, remain a promising alternative for tissue
      engineering. Among them, autograft is a preferred option for its safety and
      excellent biocompatibility. In this study, we utilized semitendinosus tendon
      autograft in meniscus reconstruction to investigate its fibrochondrogenic
      metaplasticity potential and chondroprotective effect. Tendon-derived stem cells
      (TDSCs) and synovial-derived mesenchymal stem cells (SMSCs), two most important
      stem cell sources in our strategy, exhibited excellent viability, distribution,
      proliferation and fibrochondrogenic differentiation ability in decellularized
      semitendinosus tendon (DST) scaffolds in vitro. Histologic evaluation of the
      tendon grafts in vivo suggested endogenous stem cells differentiated into
      fibrochondrocytes, synthesized proteoglycan, type II collagen and radial type I
      collagen at 12 weeks and 24 weeks post-surgery. As for elastic modulus and
      hardness of the grafts, there were no significant differences between native
      meniscus and regenerated meniscus at 24 weeks. The protection of condylar
      cartilage from degeneration was significantly better in the reconstruction group
      comparing to control group. Overall, semitendinosus tendon autograft seems to be
      a promising substitution in meniscus reconstruction.

PMID- 28765606
TI  - 2-Oxoesters: A Novel Class of Potent and Selective Inhibitors of Cytosolic Group
      IVA Phospholipase A2.
AB  - Cytosolic phospholipase A2 (GIVA cPLA2) is the only PLA2 that exhibits a marked
      preference for hydrolysis of arachidonic acid containing phospholipid substrates
      releasing free arachidonic acid and lysophospholipids and giving rise to the
      generation of diverse lipid mediators involved in inflammatory conditions. Thus,
      the development of potent and selective GIVA cPLA2 inhibitors is of great
      importance. We have developed a novel class of such inhibitors based on the 2
      oxoester functionality. This functionality in combination with a long aliphatic
      chain or a chain carrying an appropriate aromatic system, such as the biphenyl
      system, and a free carboxyl group leads to highly potent and selective GIVA cPLA2
      inhibitors (X I(50) values 0.00007-0.00008) and docking studies aid in
      understanding this selectivity. A methyl 2-oxoester, with a short chain carrying
      a naphthalene ring, was found to preferentially inhibit the other major
      intracellular PLA2, the calcium-independent PLA2. In RAW264.7 macrophages,
      treatment with the most potent 2-oxoester GIVA cPLA2 inhibitor resulted in over
      50% decrease in KLA-elicited prostaglandin D2 production. The novel, highly
      potent and selective GIVA cPLA2 inhibitors provide excellent tools for the study
      of the role of the enzyme and could contribute to the development of novel
      therapeutic agents for the treatment of inflammatory diseases.

PMID- 28765607
TI  - Suppression of Transposable Elements in Leukemic Stem Cells.
AB  - Genomic transposable elements (TEs) comprise nearly half of the human genome. The
      expression of TEs is considered potentially hazardous, as it can lead to
      insertional mutagenesis and genomic instability. However, recent studies have
      revealed that TEs are involved in immune-mediated cell clearance. Hypomethylating
      agents can increase the expression of TEs in cancer cells, inducing 'viral
      mimicry', causing interferon signalling and cancer cell killing. To investigate
      the role of TEs in the pathogenesis of acute myeloid leukaemia (AML), we studied
      TE expression in several cell fractions of AML while tracking its development
      (pre-leukemic haematopoietic stem cells, leukemic stem cells [LSCs], and leukemic
      blasts). LSCs, which are resistant to chemotherapy and serve as reservoirs for
      relapse, showed significant suppression of TEs and interferon pathways.
      Similarly, high-risk cases of myelodysplastic syndrome (MDS) showed far greater
      suppression of TEs than low-risk cases. We propose TE suppression as a mechanism
      for immune escape in AML and MDS. Repression of TEs co-occurred with the
      upregulation of several genes known to modulate TE expression, such as RNA
      helicases and autophagy genes. Thus, we have identified potential pathways that
      can be targeted to activate cancer immunogenicity via TEs in AML and MDS.

PMID- 28765608
TI  - Endocannabinoid Modulation of Stimulus-Specific Adaptation in Inferior Colliculus
      Neurons of the Rat.
AB  - Cannabinoid receptors (CBRs) are widely distributed in the brain, including the
      inferior colliculus (IC). Here, we aim to study whether endocannabinoids
      influence a specific type of neuronal adaptation, namely, stimulus-specific
      adaptation (SSA) found in some IC neurons. SSA is important because it has been
      found as early as the level of the midbrain and therefore it may be a neuronal
      correlate of early indices of deviance detection. Furthermore, recent studies
      have demonstrated a direct link between SSA and MMN, that is widely used as an
      outcome measure in a variety of human neurodegenerative disorders. SSA is
      considered a form of short-term plasticity, and CBRs have been shown to play a
      role in short-term neural plasticity. Therefore, it is reasonable to hypothesize
      that endocannabinoids may play a role in the generation or modulation of SSA. We
      recorded single units in the IC under an oddball paradigm stimulation. The
      results demonstrate that cannabinoid agonists lead to a reduction in the neuronal
      adaptation. This change is due to a differential increase of the neuronal firing
      rate to the standard tone alone. Furthermore, we show that the effect is mediated
      by the cannabinoid receptor 1 (CBR1). Thus, cannabinoid agonists down-modulate
      SSA in IC neurons.

PMID- 28765609
TI  - Effects of placental cord drainage in the third stage of labour: A meta-analysis.
AB  - Observational studies have demonstrated that placental cord drainage can shorten
      the length of the third stage of labour and reduce blood loss during vaginal
      deliveries. The aim of our work was to evaluate the existing evidence for the
      effectiveness of placental cord drainage in the third stage of labour. PubMed,
      Embase, the Cochrane Library, Web of Science, Google Scholar and 50 journals were
      searched up to the 4th of June, 2017. Randomized controlled trials comparing
      placental cord drainage with no cord drainage in the third stage of labour during
      vaginal delivery were included. Nine studies with 2653 participants were
      included. Compared with clamping the umbilical cord, umbilical cord drainage
      during the third stage of labour shortened the third-stage duration by 2.28
      minutes (95% confidence interval (CI), -3.22 to -1.33), but did not reduce the
      amount of blood loss (-31.99 mL, -86.08 to 22.09). For women with normal vaginal
      deliveries, the incidence of postpartum haemorrhage was reduced by 3%. Placental
      cord drainage is a simple and non-invasive procedure that should be considered
      after delayed cord clamping. Further studies about the physiological processes
      and effects of placental cord drainage in additional circumstances are needed.

PMID- 28765610
TI  - High Mobility Group Box 1 Protein Level as a Novel Biomarker for the Development
      of Peri-Implant Disease.
AB  - Peri-implant disease is a chronic inflammation of the soft and hard tissues
      around a dental implant, resulting from bacterial infection. Recent evidence
      indicates that some pro-inflammatory cytokines and chemokines released by
      immunocytes are substantially responsible for the progress and consequence of
      inflammation. High mobility group box 1 (HMGB1) is released into the
      extracellular matrix and acts as a key pro-inflammatory factor during injury,
      necrosis and inflammation. A higher concentration of HMGB1 has been found in
      gingival crevicular fluid from inflammatory gingival tissue than from healthy
      sites. HMGB1 mRNA and protein are overexpressed in murine periodontal ligament
      fibroblasts stimulated with lipopolysaccharide (LPS) and IL-1beta. Thus, this
      study sought to assess HMGB1 expression in peri-implant crevicular fluid (PICF)
      at each stage of peri-implant disease and to investigate the correlation between
      HMGB1 and peri-implant disease progress. The results demonstrated that the HMGB1
      expression level in PICF is indicative of the progress of peri-implant disease
      and hence may be a useful diagnostic and prognostic biomarker for peri-implant
      tissue.

PMID- 28765611
TI  - The differentiation of ROR-gammat expressing iNKT17 cells is orchestrated by
      Runx1.
AB  - iNKT cells are a unique lineage of T cells that recognize glycolipid presented by
      CD1d. In the thymus, they differentiate into iNKT1, iNKT2 and iNKT17 effector
      subsets, characterized by preferential expression of Tbet, Gata3 and ROR-gammat
      and production of IFN-gamma, IL-4 and IL-17, respectively. We demonstrate that
      the transcriptional regulator Runx1 is essential for the generation of ROR-gammat
      expressing iNKT17 cells. PLZF-cre Runx1 cKO mice lack iNKT17 cells in the thymus,
      spleen and liver. Runx1-deficient iNKT cells have altered expression of several
      genes important for iNKT17 differentiation, including decreased expression of IL
      7Ralpha, BATF and c-Maf and increased expression of Bcl11b and Lef1. However,
      reduction of Lef1 expression or introduction of an IL-7Ralpha transgene is not
      sufficient to correct the defect in iNKT17 differentiation, demonstrating that
      Runx1 is a key regulator of several genes required for iNKT17 differentiation.
      Loss of Runx1 leads to a severe decrease in iNKT cell numbers in the thymus,
      spleen and liver. The decrease in cell number is due to a combined decrease in
      proliferation at Stage 1 during thymic development and increased apoptosis. Thus,
      we describe a novel role of Runx1 in iNKT cell development and differentiation,
      particularly in orchestrating iNKT17 differentiation.

PMID- 28765612
TI  - Pediatric Sarcoma Data Forms a Unique Cluster Measured via the Earth Mover's
      Distance.
AB  - In this note, we combined pediatric sarcoma data from Columbia University with
      adult sarcoma data collected from TCGA, in order to see if one can automatically
      discern a unique pediatric cluster in the combined data set. Using a novel
      clustering pipeline based on optimal transport theory, this turned out to be the
      case. The overall methodology may find uses for the classification of data from
      other biological networking problems.

PMID- 28765613
TI  - Structural and functional identification of vasculogenic mimicry in vitro.
AB  - Vasculogenic mimicry (VM) describes a process by which cancer cells establish an
      alternative perfusion pathway in an endothelial cell-free manner. Despite its
      strong correlation with reduced patient survival, controversy still surrounds the
      existence of an in vitro model of VM. Furthermore, many studies that claim to
      demonstrate VM fail to provide solid evidence of true hollow channels, raising
      concerns as to whether actual VM is actually being examined. Herein, we provide a
      standardized in vitro assay that recreates the formation of functional hollow
      channels using ovarian cancer cell lines, cancer spheres and primary cultures
      derived from ovarian cancer ascites. X-ray microtomography 3D-reconstruction,
      fluorescence confocal microscopy and dye microinjection conclusively confirm the
      existence of functional glycoprotein-rich lined tubular structures in vitro and
      demonstrate that many of structures reported in the literature may not represent
      VM. This assay may be useful to design and test future VM-blocking anticancer
      therapies.

PMID- 28765614
TI  - Hierarchy in the home cage affects behaviour and gene expression in group-housed
      C57BL/6 male mice.
AB  - Group-housed male mice exhibit aggressive behaviour towards their cage mates and
      form a social hierarchy. Here, we describe how social hierarchy in standard group
      housed conditions affects behaviour and gene expression in male mice. Four male
      C57BL/6 mice were kept in each cage used in the study, and the social hierarchy
      was determined from observation of video recordings of aggressive behaviour.
      After formation of a social hierarchy, the behaviour and hippocampal gene
      expression were analysed in the mice. Higher anxiety- and depression-like
      behaviours and elevated gene expression of hypothalamic corticotropin-releasing
      hormone and hippocampal serotonin receptor subtypes were observed in subordinate
      mice compared with those of dominant mice. These differences were alleviated by
      orally administering fluoxetine, which is an antidepressant of the selective
      serotonin reuptake inhibitor class. We concluded that hierarchy in the home cage
      affects behaviour and gene expression in male mice, resulting in anxiety- and
      depression-like behaviours being regulated differently in dominant and
      subordinate mice.

PMID- 28765615
TI  - The phenotypic variability of HK1-associated retinal dystrophy.
AB  - Inherited retinal dystrophies (IRDs) are a clinically and genetically
      heterogeneous group of Mendelian disorders primarily affecting photoreceptor
      cells. The same IRD-causing variant may lead to different retinal symptoms,
      demonstrating pleiotropic phenotype traits influenced by both underlying genetic
      and environmental factors. In the present study, we identified four unrelated IRD
      families with the HK1 p.E851K variant, which was previously reported to cause
      autosomal dominant retinitis pigmentosa (RP), and described their detailed
      clinical phenotypes. Interestingly, we found that in addition to RP, this
      particular variant can also cause dominant macular dystrophy and cone-rod
      dystrophy, which primarily affect cone photoreceptors instead of rods. Our
      results identified pleiotropic effects for an IRD-causing variant and provide
      more insights into the involvement of a hexokinase in retinal pathogenesis.

PMID- 28765616
TI  - Vitamin D receptor and calcium-sensing receptor polymorphisms and colorectal
      cancer survival in the Newfoundland population.
AB  - BACKGROUND: Increased serum levels of vitamin D and calcium have been associated
      with lower risks of colorectal cancer (CRC) incidence and mortality. These
      inverse associations may be mediated by the vitamin D receptor (VDR) and the
      calcium-sensing receptor (CASR). We investigated genetic variants in VDR and CASR
      for their relevance to CRC prognosis. METHODS: A population-based cohort of 531
      CRC patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada,
      was followed for mortality and cancer recurrence until April 2010. Germline DNA
      samples were genotyped with the Illumina Omni-Quad 1 Million chip. Multivariate
      Cox models assessed 41 tag single-nucleotide polymorphisms and relative
      haplotypes on VDR and CASR in relation to all-cause mortality (overall survival,
      OS) and disease-free survival (DFS). RESULTS: Gene-level associations were
      observed between VDR and the DFS of rectal cancer patients (P=0.037) as well as
      between CASR and the OS of colon cancer patients (P=0.014). Haplotype analysis
      within linkage blocks of CASR revealed the G-G-G-G-G-A-C haplotype (rs10222633
      rs10934578-rs3804592-rs17250717-A986S-R990G-rs1802757) to be associated with a
      decreased OS of colon cancer (HR, 3.15; 95% CI, 1.66-5.96). Potential
      interactions were seen among prediagnostic dietary calcium intake with the CASR
      R990G (Pint=0.040) and the CASR G-T-G-G-G-G-C haplotype for rs10222633-rs10934578
      rs3804592-rs17250717-A986S-R990G-rs1802757 (Pint=0.017), with decreased OS time
      associated with these variants limited to patients consuming dietary calcium
      below the median, although the stratified results were not statistically
      significant after correction for multiple testing. CONCLUSIONS: Polymorphic
      variations in VDR and CASR may be associated with survival after a diagnosis of
      CRC.

PMID- 28765619
TI  - Reference gene selection to determine differences in mitochondrial gene
      expressions in phosphine-susceptible and phosphine-resistant strains of
      Cryptolestes ferrugineus, using qRT-PCR.
AB  - Cryptolestes ferrugineus is a serious pest of stored grain and has developed high
      levels of resistance to phosphine fumigants in many countries. Measuring
      differences in expression levels of certain 'resistant' genes by quantitative
      real-time PCR (qRT-PCR) may provide insights into molecular mechanisms underlying
      resistance to phosphine in C. ferrugineus, but reliable qRT-PCR results depend on
      suitable reference genes (RGs). We evaluated the stability of nine candidate RGs
      across different developmental stages and phosphine strains of C. ferrugineus,
      using four softwares. The results showed that RPS13 and EF1alpha were the most
      stable RGs, whereas alpha-TUB was the least under developmental stages. Across
      the different strains, RPS13 and gamma-TUB were the most stable RGs, whereas CycA
      and GAPDH were the least. We confirmed the reliability of the selected RGs by qRT
      PCR analyses of the mitochondrial cox1 gene. Expression of cox1 was not
      significantly different in the phosphine-resistant strain compared with the
      phosphine-susceptible strain, but three mitochondrial genes (nad3, atp6 and cob)
      were significantly down-regulated. These results suggest that alterations in the
      expressions of these three genes may be associated with phosphine resistance in
      C. ferrugineus. The findings will facilitate future functional genomics studies
      on the development and phosphine resistance in C. ferrugineus.

PMID- 28765620
TI  - The Oxygen Reduction Reaction Rate of Metallic Nanoparticles during Catalyzed
      Oxidation.
AB  - This work reports the oxygen reduction reaction (ORR) kinetics of metal
      nanoparticle catalysts between 500 and 600  degrees C at low oxygen partial
      pressures. Ex situ and in situ TEM measurements demonstrate catalyzed nanowire
      growth initially follows linear kinetics; characteristic of being ORR rate
      limited. The ORR rates of Ag, Au, Cu, Ni, Pd, Rh and Pt measured at 600  degrees
      C form a volcano plot versus relative oxidation potential. Cu nanoparticles
      produce the maximum ORR rate under these conditions.

PMID- 28765618
TI  - Lauren subtypes of advanced gastric cancer influence survival and response to
      chemotherapy: real-world data from the AGAMENON National Cancer Registry.
AB  - BACKGROUND: The choice of chemotherapy in HER2-negative gastric cancer is based
      on centre's preferences and adverse effects profile. No schedule is currently
      accepted as standard, nor are there any factors to predict response, other than
      HER2 status. We seek to evaluate whether Lauren type influences the efficacy of
      various chemotherapies and on patient overall survival (OS). METHODS: We have
      conducted a multicenter study in 31 hospitals. The eligibility criteria include
      diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2
      negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards
      regression adjusted for confounding factors, with tests of 'treatment-by
      histology' interaction, was used to estimate treatment effect. RESULTS: Our
      registry contains 1303 tumours analysable for OS end points and 730 evaluable for
      overall response rate (ORR). A decrease in ORR was detected in the presence of a
      diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987),
      P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in
      the intestinal type. The diffuse type displayed increased mortality with hazard
      ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving
      chemotherapy with docetaxel exhibited increased OS limited to the intestinal
      type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the
      subset having a diffuse component. With respect to progression-free survival
      (PFS), a significant interaction was seen in the effect of docetaxel-containing
      schedules, with better PFS limited to the intestinal type subgroup, in the
      comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and
      against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046.
      CONCLUSIONS: As a conclusion, in this registry, Lauren classification tumour
      subtypes predicted survival and responded differently to chemotherapy. Future
      clinical trials should stratify effect estimations based on histology.

PMID- 28765621
TI  - Monolithic mode-selective few-mode multicore fiber multiplexers.
AB  - With the capacity limits of standard single-mode optical fiber fast approaching,
      new technologies such as space-division multiplexing are required to avoid an
      Internet capacity crunch. Few-mode multicore fiber (FM-MCF) could allow for a two
      orders of magnitude increase in capacity by using the individual spatial modes in
      the different cores as unique data channels. We report the realization of a
      monolithic mode-selective few-mode multicore fiber multiplexer capable of
      addressing the individual modes of such a fiber. These compact multiplexers
      operate across the S + C + L telecommunications bands and were inscribed into a
      photonic chip using ultrafast laser inscription. They allow for the simultaneous
      multiplexing of the LP01, LP11a and LP11b modes of all cores in a 3-mode, 4-core
      fiber with excellent mode extinction ratios and low insertion losses. The devices
      are scalable to more modes and cores and therefore could represent an enabling
      technology for practical ultra-high capacity dense space-division multiplexing.

PMID- 28765622
TI  - Interplay between social influence and competitive strategical games in multiplex
      networks.
AB  - We present a model that takes into account the coupling between evolutionary game
      dynamics and social influence. Importantly, social influence and game dynamics
      take place in different domains, which we model as different layers of a
      multiplex network. We show that the coupling between these dynamical processes
      can lead to cooperation in scenarios where the pure game dynamics predicts
      defection. In addition, we show that the structure of the network layers and the
      relation between them can further increase cooperation. Remarkably, if the layers
      are related in a certain way, the system can reach a polarized metastable state.
      These findings could explain the prevalence of polarization observed in many
      social dilemmas.

PMID- 28765617
TI  - Height, selected genetic markers and prostate cancer risk: results from the
      PRACTICAL consortium.
AB  - BACKGROUND: Evidence on height and prostate cancer risk is mixed, however, recent
      studies with large data sets support a possible role for its association with the
      risk of aggressive prostate cancer. METHODS: We analysed data from the PRACTICAL
      consortium consisting of 6207 prostate cancer cases and 6016 controls and a
      subset of high grade cases (2480 cases). We explored height, polymorphisms in
      genes related to growth processes as main effects and their possible
      interactions. RESULTS: The results suggest that height is associated with high
      grade prostate cancer risk. Men with height >180 cm are at a 22% increased risk
      as compared to men with height <173 cm (OR 1.22, 95% CI 1.01-1.48). Genetic
      variants in the growth pathway gene showed an association with prostate cancer
      risk. The aggregate scores of the selected variants identified a significantly
      increased risk of overall prostate cancer and high-grade prostate cancer by 13%
      and 15%, respectively, in the highest score group as compared to lowest score
      group. CONCLUSIONS: There was no evidence of gene-environment interaction between
      height and the selected candidate SNPs.Our findings suggest a role of height in
      high-grade prostate cancer. The effect of genetic variants in the genes related
      to growth is seen in all cases and high-grade prostate cancer. There is no
      interaction between these two exposures.

PMID- 28765623
TI  - Lagrangian dynamical geography of the Gulf of Mexico.
AB  - We construct a Markov-chain representation of the surface-ocean Lagrangian
      dynamics in a region occupied by the Gulf of Mexico (GoM) and adjacent portions
      of the Caribbean Sea and North Atlantic using satellite-tracked drifter
      trajectory data, the largest collection so far considered. From the analysis of
      the eigenvectors of the transition matrix associated with the chain, we identify
      almost-invariant attracting sets and their basins of attraction. With this
      information we decompose the GoM's geography into weakly dynamically interacting
      provinces, which constrain the connectivity between distant locations within the
      GoM. Offshore oil exploration, oil spill contingency planning, and fish larval
      connectivity assessment are among the many activities that can benefit from the
      dynamical information carried in the geography constructed here.

PMID- 28765624
TI  - Metacognitive Deficiency in a Perceptual but Not a Memory Task in Methadone
      Maintenance Patients.
AB  - Drug addiction has been associated with lack of insight into one's own abilities.
      However, the scope of metacognition impairment among drug users in general and
      opiate dependent individuals in particular is not fully understood. Investigating
      the impairments of metacognitive ability in Substance Dependent Individuals
      (SDIs) in different cognitive tasks could contribute to the ongoing debate over
      whether metacognition has domain-general or domain-specific neural substrates. We
      compared metacognitive self-monitoring ability of a group of SDIs during
      methadone maintenance treatment (n = 23) with a control group (n = 24) in a
      memory and a visual perceptual task. Post decision self judgements of probability
      of correct choice were obtained through trial by trial confidence ratings and
      were used to compute metacognitive ability. Results showed that despite
      comparable first order performance in the perceptual task, SDIs had lower
      perceptual metacognition than the control group. However, although SDIs had
      poorer memory performance, their metacognitive judgements in the memory task were
      as accurate as the control group. While it is commonly believed that addiction
      causes pervasive impairment in cognitive functions, including metacognitive
      ability, we observed that the impairment was only significant in one specific
      task, the perceptual task, but not in the memory task.

PMID- 28765625
TI  - Blood-testis barrier integrity depends on Pin1 expression in Sertoli cells.
AB  - The conformation and function of a subset of serine and threonine-phosphorylated
      proteins are regulated by the prolyl isomerase Pin1 through isomerization of
      phosphorylated Ser/Thr-Pro bonds. Pin1 is intensely expressed in Sertoli cells,
      but its function in this post mitotic cell remains unclear. Our aim was to
      investigate the role of Pin1 in the Sertoli cells. Lack of Pin1 caused disruption
      of the blood-testis barrier. We next investigated if the activin pathways in the
      Sertoli cells were affected by lack of Pin1 through immunostaining for Smad3
      protein in testis tissue. Indeed, lack of Pin1 caused reduced Smad3 expression in
      the testis tissue, as well as a reduction in the level of N-Cadherin, a known
      target of Smad3. Pin1-/- testes express Sertoli cell marker mRNAs in a pattern
      similar to that seen in Smad3+/- mice, except for an increase in Wt1 expression.
      The resulting dysregulation of N-Cadherin, connexin 43, and Wt1 targets caused by
      lack of Pin1 might affect the mesenchymal-epithelial balance in the Sertoli cells
      and perturb the blood-testis barrier. The effect of Pin1 dosage in Sertoli cells
      might be useful in the study of toxicant-mediated infertility, gonadal cancer,
      and for designing male contraceptives.

PMID- 28765626
TI  - Motorboat noise disrupts co-operative interspecific interactions.
AB  - Human-made noise is contributing increasingly to ocean soundscapes. Its physical,
      physiological and behavioural effects on marine organisms are potentially
      widespread, but our understanding remains largely limited to intraspecific
      impacts. Here, we examine how motorboats affect an interspecific cleaning
      mutualism critical for coral reef fish health, abundance and diversity. We
      conducted in situ observations of cleaning interactions between bluestreak
      cleaner wrasses (Labroides dimidiatus) and their fish clients before, during and
      after repeated, standardised approaches with motorboats. Cleaners inspected
      clients for longer and were significantly less cooperative during exposure to
      boat noise, and while motorboat disturbance appeared to have little effect on
      client behaviour, as evidenced by consistency of visit rates, clientele
      composition, and use of cleaning incitation signals, clients did not retaliate as
      expected (i.e., by chasing) in response to increased cheating by cleaners. Our
      results are consistent with the idea of cognitive impairments due to distraction
      by both parties. Alternatively, cleaners might be taking advantage of distracted
      clients to reduce their service quality. To more fully understand the importance
      of these findings for conservation and management, further studies should
      elucidate whether the efficacy of ectoparasite removal by cleaners is affected
      and explore the potential for habituation to boat noise in busy areas.

PMID- 28765627
TI  - Value of shear wave arrival time contour display in shear wave elastography for
      breast masses diagnosis.
AB  - To evaluate the diagnostic performance of shear wave arrival time contour (SWATC)
      display for the diagnosis of breast lesions and to identify factors associated
      with the quality of shear wave propagation (QSWP) in breast lesions. This study
      included 277 pathologically confirmed breast lesions. Conventional B-mode
      ultrasound characteristics and shear wave elastography parameters were computed.
      Using the SWATC display, the QSWP of each lesion was assigned to a two-point
      scale: score 1 (low quality) and score 2 (high quality). Binary logistic
      regression analysis was performed to identify factors associated with QSWP. The
      area under the receiver operating characteristic curve (AUROC) for QSWP to
      differentiate benign from malignant lesions was 0.913, with a sensitivity of
      91.9%, a specificity of 90.7%, a positive predictive value (PPV) of 74.0%, and a
      negative predictive value (NPV) of 97.5%. Compared with using the standard
      deviation of shear wave speed (SWSSD) alone, SWSSD combined with QSWP increased
      the sensitivity from 75.8% to 93.5%, but decreased the specificity from 95.8% to
      89.3% (P < 0.05). SWSSD was identified to be the strongest factor associated with
      the QSWP, followed by tumor malignancy and the depth of the lesion. In
      conclusion, SWATC display may be useful for characterization of breast lesions.

PMID- 28765628
TI  - NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically
      ill patients.
AB  - Sclerosing cholangitis in critically ill patients (SC-CIP) is a progressive
      cholestatic disease of unknown aetiology characterized by chronic biliary
      infections. Hence we hypothesized that common NOD2 (nucleotide-binding
      oligomerisation domain containing 2) gene variants, known risk factors for
      Crohn's disease and bacterial translocation in liver cirrhosis, increase the odds
      of developing SC-CIP. Screening of 4,641 endoscopic retrograde cholangiography
      procedures identified 17 patients with SC-CIP, who were then genotyped for the
      three common NOD2 mutations (Cohort 1, discovery cohort). To validate the
      association, we subsequently tested these NOD2 variants in 29 patients from SC
      CIP cohorts of three additional medical centers (Cohort 2, replication cohort).
      In Cohort 1, the NOD2 variants were present in 5 of 17 SC-CIP patients (29.4%),
      which is twice the frequency of the general population. These results were
      replicated in Cohort 2 with 8 patients (27.6%) showing NOD2 mutations. In
      contrast, polymorphisms of hepatocanalicular transporter genes did not have major
      impact on SC-CIP risk. This first study on genetic susceptibility in SC-CIP
      patients shows an extraordinary high frequency of NOD2 variation, pointing to a
      critical role of inherited impaired anti-bacterial defense in the development of
      this devastating biliary disease.

PMID- 28765629
TI  - Subthalamic nucleus stimulation and levodopa modulate cardiovascular autonomic
      function in Parkinson's disease.
AB  - We aimed to explore the effects of bilateral subthalamic nucleus stimulation and
      levodopa on cardiovascular autonomic function in Parkinson's disease. Twenty-six
      Parkinson's disease patients with bilateral subthalamic nucleus stimulation in a
      stable state were tested under stimulation off and dopaminergic medication off
      (OFF-OFF), stimulation on and dopaminergic medication off (ON-OFF), and
      stimulation on and medication (levodopa) on (ON-ON) conditions by recording
      continuously blood pressure, ECG, and respiration at rest, during metronomic deep
      breathing, and head-up tilt test. Thirteen patients were diagnosed as orthostatic
      hypotension by head-up tilt test. Baroreflex sensitivity and spectral analyses
      were performed by trigonometric regressive spectral analysis. Subthalamic nucleus
      stimulation and levodopa had multiple influences. (1) Systolic blood pressure
      during tilt-up was reduced by subthalamic nucleus stimulation, and then further
      by levodopa. (2) Subthalamic nucleus stimulation and levodopa had different
      effects on sympathetic and parasympathetic regulations in Parkinson's disease.
      (3) Levodopa decreased baroreflex sensitivity and RR interval only in the
      orthostatic hypotension group, and had opposite effects on the non-orthostatic
      hypotension group. These findings indicate that subthalamic nucleus stimulation
      and levodopa have different effects on cardiovascular autonomic function in
      Parkinson's disease, which are modulated by the presence of orthostatic
      hypotension as well.

PMID- 28765630
TI  - Carbon black as an alternative cathode material for electrical energy recovery
      and transfer in a microbial battery.
AB  - Rather than the conventional concept of viewing conductive carbon black (CB) to
      be chemically inert in microbial electrochemical cells (MECs), here we confirmed
      the redox activity of CB for its feasibility as an electron sink in the microbial
      battery (MB). Acting as the cathode of a MB, the solid-state CB electrode showed
      the highest electron capacity equivalent of 18.58 +/- 0.46 C/g for the unsintered
      one and the lowest capacity of 2.29 +/- 0.48 C/g for the one sintered under 100%
      N2 atmosphere. The capacity vibrations of CBs were strongly in coincidence with
      the abundances of C=O moiety caused by different pretreatments and it implied one
      plausible mechanism based on CB's surface functionality for its electron
      capturing. Once subjected to electron saturation, CB could be completely
      regenerated by different strategies in terms of electrochemical discharging or
      donating electrons to biologically-catalyzed nitrate reduction. Surface
      characterization also revealed that CB's regeneration fully depended on the
      reversible shift of C=O moiety, further confirming the functionality-based
      mechanism for CB's feasibility as the role of MB's cathode. Moreover, resilience
      tests demonstrated that CB cathode was robust for the multi-cycles charging
      discharging operations. These results imply that CB is a promising alternative
      material for the solid-state cathode in MBs.

PMID- 28765631
TI  - Transferring arbitrary d-dimensional quantum states of a superconducting transmon
      qudit in circuit QED.
AB  - A qudit (d-level quantum system) has a large Hilbert space and thus can be used
      to achieve many quantum information and communication tasks. Here, we propose a
      method to transfer arbitrary d-dimensional quantum states (known or unknown)
      between two superconducting transmon qudits coupled to a single cavity. The state
      transfer can be performed by employing resonant interactions only. In addition,
      quantum states can be deterministically transferred without measurement.
      Numerical simulations show that high-fidelity transfer of quantum states between
      two superconducting transmon qudits (d <= 5) is feasible with current circuit QED
      technology. This proposal is quite general and can be applied to accomplish the
      same task with natural or artificial atoms of a ladder-type level structure
      coupled to a cavity or resonator.

PMID- 28765632
TI  - Efficient increase of gamma-aminobutyric acid (GABA) content in tomato fruits by
      targeted mutagenesis.
AB  - gamma-Aminobutyric acid (GABA) is a non-proteinogenic amino acid that has
      hypotensive effects. Tomato (Solanum lycopersicum L.) is among the most widely
      cultivated and consumed vegetables in the world and contains higher levels of
      GABA than other major crops. Increasing these levels can further enhance the
      blood pressure-lowering function of tomato fruit. Glutamate decarboxylase (GAD)
      is a key enzyme in GABA biosynthesis; it has a C-terminal autoinhibitory domain
      that regulates enzymatic function, and deleting this domain increases GAD
      activity. The tomato genome has five GAD genes (SlGAD1-5), of which two (SlGAD2
      and SlGAD3) are expressed during tomato fruit development. To increase GABA
      content in tomato, we deleted the autoinhibitory domain of SlGAD2 and SlGAD3
      using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated protein (Cas)9 technology. Introducing a stop codon immediately before
      the autoinhibitory domain increased GABA accumulation by 7 to 15 fold while
      having variable effects on plant and fruit size and yield. This is the first
      study describing the application of the CRISPR/Cas9 system to increase GABA
      content in tomato fruits. Our findings provide a basis for the improvement of
      other types of crop by CRISPR/Cas9-based genetic modification.

PMID- 28765633
TI  - Performance measurement of intraoperative systolic arterial pressure to predict
      in-hospital mortality in adult liver transplantation.
AB  - Profound hypotension during liver transplantation is aggressively treated with
      vasopressors thus frequently unrevealed in a retrospective study. The
      relationship between concealed intraoperative hypotension and in-hospital
      mortality after liver transplantation was evaluated using performance measurement
      (PM) of systolic arterial pressure (SAP). Median performance error (MDPE), median
      absolute performance error (MDAPE), and wobble of SAP were calculated using
      preoperative SAP as the reference value, and prereperfusion and postreperfusion
      SAPs as measured values. Univariable and multivariable logistic regression
      analyses were performed using 6 PM parameters and 36 traditional SAP-derived
      parameters to predict in-hospital mortality. In-hospital mortality was 3.9%
      (22/569 cases). Prereperfusion MDAPE and postreperfusion wobble were the only
      significant SAP-derived predictors of in-hospital mortality. The area under
      receiver operating characteristic curve of prediction model was 0.769 (95%
      confidence interval 0.732-0.803, P < 0.001; sensitivity = 55%, specificity =
      94%). Severe hypotension during liver transplantation is concealed by proactive
      vasopressor treatment thus traditional measures of hypotension generally fail to
      detect the masked hypotension in retrospective analysis. PM analysis of
      intraoperative SAP including prereperfusion MDAPE and postreperfusion wobble is
      most likely to detect treated and therefore concealed hypotension, and was able
      to independently and quantitatively predict in-hospital mortality after liver
      transplantation with high diagnostic specificity.

PMID- 28765634
TI  - Hybrid organic-inorganic coatings via electron transfer behaviour.
AB  - A novel method to functionalize the surface of inorganic coating by growing
      organic coating has been investigated based on microstructural interpretation,
      electrochemical assessment, and quantum chemical analysis. For this purpose,
      inorganic coating with magnesium aluminate, magnesium oxide, and titanium dioxide
      was prepared on magnesium alloy via plasma electrolytic oxidation (PEO), and,
      then, subsequent dip-coating method was used to tailor organic coating using
      diethyl-5-hydroxyisophthalate (DEIP) as organic molecules. The incorporation of
      TiO2 particles worked as a sealing agent to block the micro-defects which
      resulted mainly from the intense plasma sparks during PEO. In addition, such
      incorporation played an important role in enhancing the adhesion between
      inorganic and organic coatings. The use of DEIP as organic corrosion inhibitor
      resulted in a significant decrease in porosity of inorganic coating. Quantum
      chemical calculation was used to clarify the corrosion inhibition mechanism which
      was activated by introduction of DEIP. Thus, the electrochemical analysis based
      on potentiodynamic polarization and impedance spectroscopy tests in 3.5 wt% NaCl
      solution suggested that corrosion resistance of magnesium alloy sample was
      enhanced significantly due to a synergistic effect arising from the hybrid
      inorganic and organic coatings. This phenomenon was explained in relation to
      electron transfer behaviour between inorganic and organic coatings.

PMID- 28765635
TI  - Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates
      osteoarthritic progression in a mice model.
AB  - The catabolism of hyaluronan in articular cartilage remains unclear. The aims of
      this study were to investigate the effects of hyaluronidase 2 (Hyal2) knockdown
      in articular cartilage on the development of osteoarthritis (OA) using genetic
      manipulated mice. Destabilization of the medial meniscus (DMM) model of Col2a
      promoter specific conditional Hyal2 knockout (Hyal -/- ) mice was established and
      examined. Age related and DMM induced alterations of articular cartilage of knee
      joint were evaluated with modified Mankin score and immunohistochemical staining
      of MMP-13, ADAMTS-5, KIAA11199, and biotinylated- hyaluronan binding protein
      staining in addition to histomorphometrical analyses. Effects of Hyal2
      suppression were also analyzed using explant culture of an IL-1alpha induced
      articular cartilage degradation model. The amount and size of hyaluronan in
      articular cartilage were higher in Hyal2 -/- mice. Hyal2 -/- mice exhibited
      aggravated cartilage degradation in age-related and DMM induced mice. MMP-13 and
      ADAMTS-5 positive chondrocytes were significantly higher in Hyal2 -/- mice.
      Articular cartilage was more degraded in explant cultures obtained from Hyal2 -/-
      mice. Knockdown of Hyal2 in articular cartilage induced OA development and
      progression possibly mediated by an imbalance of HA metabolism. This suggests
      that Hyal2 knockdown exhibits mucopolysaccharidosis-like OA change in articular
      cartilage similar to Hyal1 knockdown.

PMID- 28765636
TI  - High-Resolution Patterned Cellular Constructs by Droplet-Based 3D Printing.
AB  - Bioprinting is an emerging technique for the fabrication of living tissues that
      allows cells to be arranged in predetermined three-dimensional (3D)
      architectures. However, to date, there are limited examples of bioprinted
      constructs containing multiple cell types patterned at high-resolution. Here we
      present a low-cost process that employs 3D printing of aqueous droplets
      containing mammalian cells to produce robust, patterned constructs in oil, which
      were reproducibly transferred to culture medium. Human embryonic kidney (HEK)
      cells and ovine mesenchymal stem cells (oMSCs) were printed at tissue-relevant
      densities (107 cells mL-1) and a high droplet resolution of 1 nL. High-resolution
      3D geometries were printed with features of <=200 MUm; these included an
      arborised cell junction, a diagonal-plane junction and an osteochondral
      interface. The printed cells showed high viability (90% on average) and HEK cells
      within the printed structures were shown to proliferate under culture conditions.
      Significantly, a five-week tissue engineering study demonstrated that printed
      oMSCs could be differentiated down the chondrogenic lineage to generate cartilage
      like structures containing type II collagen.

PMID- 28765637
TI  - A Study of the Dynamic Relation between Physiological Changes and Spontaneous
      Expressions.
AB  - Recent progress in Affective Computing (AC) has enabled integration of
      physiological cues and spontaneous expressions to reveal a subject's emotional
      state. Due to the lack of an effective technique for evaluating multimodal
      correlations, experience and intuition play a main role in present AC studies
      when fusing affective cues or modalities, resulting in unexpected outcomes. This
      study seeks to demonstrate a dynamic correlation between two such affective cues,
      physiological changes and spontaneous expressions, which were obtained by a
      combination of stereo vision based tracking and imaging photoplethysmography
      (iPPG), with a designed protocol involving 20 healthy subjects. The two cues
      obtained were sampled into a Statistical Association Space (SAS) to evaluate
      their dynamic correlation. It is found that the probability densities in the SAS
      increase as the peaks in two cues are approached. Also the complex form of the
      high probability density region in the SAS suggests a nonlinear correlation
      between two cues. Finally the cumulative distribution on the zero time-difference
      surface is found to be small (<0.047) demonstrating a lack of simultaneity. These
      results show that the two cues have a close interrelation, that is both
      asynchronous and nonlinear, in which a peak of one cue heralds a peak in the
      other.

PMID- 28765638
TI  - 3D reconstruction of laser projective point with projection invariant generated
      from five points on 2D target.
AB  - Vision measurement on the basis of structured light plays a significant role in
      the optical inspection research. The 2D target fixed with a line laser projector
      is designed to realize the transformations among the world coordinate system, the
      camera coordinate system and the image coordinate system. The laser projective
      point and five non-collinear points that are randomly selected from the target
      are adopted to construct a projection invariant. The closed form solutions of the
      3D laser points are solved by the homogeneous linear equations generated from the
      projection invariants. The optimization function is created by the parameterized
      re-projection errors of the laser points and the target points in the image
      coordinate system. Furthermore, the nonlinear optimization solutions of the world
      coordinates of the projection points, the camera parameters and the lens
      distortion coefficients are contributed by minimizing the optimization function.
      The accuracy of the 3D reconstruction is evaluated by comparing the displacements
      of the reconstructed laser points with the actual displacements. The effects of
      the image quantity, the lens distortion and the noises are investigated in the
      experiments, which demonstrate that the reconstruction approach is effective to
      contribute the accurate test in the measurement system.

PMID- 28765639
TI  - Experimental evidence of high pressure decoupling between charge transport and
      structural dynamics in a protic ionic glass-former.
AB  - In this paper the relaxation dynamics of ionic glass-former acebutolol
      hydrochloride (ACB-HCl) is studied as a function of temperature and pressure by
      using dynamic light scattering and broadband dielectric spectroscopy. These
      unique experimental data provide the first direct evidence that the decoupling
      between the charge transport and structural relaxation exists in proton
      conductors over a wide T-P thermodynamic space, with the time scale of structural
      relaxation being constant at the liquid-glass transition (taualpha = 1000 s). We
      demonstrate that the enhanced proton transport, being a combination of
      intermolecular H+ hopping between cation and anion as well as tautomerization
      process within amide moiety of ACB molecule, results in a breakdown of the Stokes
      Einstein relation at ambient and elevated pressure with the fractional exponent k
      being pressure dependent. The dT g /dP coefficient, stretching exponent betaKWW
      and dynamic modulus E a /DeltaV # were found to be the same regardless of the
      relaxation processes studied. This is in contrast to the apparent activation
      volume parameter that is different when charge transport and structural dynamics
      are considered. These experimental results together with theoretical
      considerations create new ideas to design efficient proton conductors for
      potential electrochemical applications.

PMID- 28765640
TI  - CVD graphene as an electrochemical sensing platform for simultaneous detection of
      biomolecules.
AB  - The development of electrochemical biosensors for the simultaneous detection of
      ascorbic acid (AA), dopamine (DA), uric acid (UA), tryptophan (Trp), and nitrite
      ([Formula: see text]) in human serum is reported in this work. Free-standing
      graphene nanosheets were fabricated on Ta wire using the chemical vapor
      deposition (CVD) method. CVD graphene, which here served as a sensing platform,
      provided a highly sensitive and selective option, with detection limits of AA,
      DA, UA, Trp, and [Formula: see text] of 1.58, 0.06, 0.09, 0.10, and 6.45 MUM (S/N
      = 3), respectively. The high selectivity of the electrode is here explained by a
      relationship between the bandgap energy of analyte and the Fermi level of
      graphene. The high sensitivity in the oxidation current was determined by
      analyzing the influence of the high surface area and chemical structure of free
      standing graphene nanosheets on analyte adsorption capacity. This finding
      strongly indicates that the CVD graphene electrode can be used as a biosensor to
      detect five analytes in human serum.

PMID- 28765641
TI  - Hypomethylation of CNTFRalpha is associated with proliferation and poor prognosis
      in lower grade gliomas.
AB  - Ciliary neurotrophic factor receptor alpha subunit (CNTFRalpha) and CNTF play
      important roles in neuron survival, glial differentiation and brain tumor growth.
      However, the molecular mechanisms of CNTFRalpha regulation and its clinical
      significance in glioma remain largely unknown. Here, we found CNTFRalpha was
      overexpressed in lower grade gliomas (LGG) compared with glioblastoma (GBM) and
      normal brain specimens in TCGA datasets and in an independent cohort.
      Bioinformatics analysis revealed a CpG shore of the CNTFRalpha gene regulated its
      mRNA expression in TCGA datasets. This observation was further validated with
      clinical specimens and functionally verified using demethylating agents.
      Additionally, we observed that independent of IDH mutation status, methylation of
      CNTFRalpha was significantly correlated with down-regulated CNTFRalpha gene
      expression and longer LGG patient survival. Interestingly, combination of
      CNTFRalpha methylation and IDH mutation significantly (p < 0.05) improved the
      prognostic prediction in LGG patients. Furthermore, the role of CNTFRalpha in
      glioma proliferation and apoptosis through the PI3K/AKT pathways was demonstrated
      by supplementation with exogenous CNTF  in vitro and siRNA knockdown in vivo. Our
      study demonstrated that hypomethylation leading to CNTFRalpha up-regulation,
      together with autocrine expression of CNTF, was involved in glioma growth
      regulation. Importantly, DNA methylation of CNTFRalpha might serve as a potential
      epigenetic theranostic target for LGG patients.

PMID- 28765642
TI  - Anti-diabetic Effects of Clostridium butyricum CGMCC0313.1 through Promoting the
      Growth of Gut Butyrate-producing Bacteria in Type 2 Diabetic Mice.
AB  - Patients with type 2 diabetes (T2D) have decreased butyrate-producing bacteria.
      We hypothesized that supplementation with butyrate-producing bacteria may exert
      beneficial effects on T2D. The current study investigated the effects of well
      characterized butyrate-producing bacteria Clostridium butyricum CGMCC0313.1
      (CB0313.1) on hyperglycemia and associated metabolic dysfunction in two diabetic
      mouse models. CB0313.1 was administered daily by oral gavage to leptin db/db mice
      for 5 weeks starting from 3 weeks of age, and to HF diabetic mice induced by high
      fat diet (HFD) plus streptozotocin (STZ) in C57BL/6J mice for 13 weeks starting
      from 4 weeks of age. CB0313.1 improved diabetic markers (fasting glucose, glucose
      tolerance, insulin tolerance, GLP-1 and insulin secretion), and decreased blood
      lipids and inflammatory tone. Furthermore, CB0313.1 reversed hypohepatias and
      reduced glucose output. We also found that CB0313.1 modulated gut microbiota
      composition, characterized by a decreased ratio of Firmicutes to Bacteroidetes,
      reduced Allobaculum bacteria that were abundant in HF diabetic mice and increased
      butyrate-producing bacteria. Changes in gut microbiota following CB0313.1
      treatment were associated with enhanced peroxisome proliferator-activated
      receptor-gamma (PPARgamma), insulin signaling molecules and mitochondrial
      function markers. Together, our study suggests that CB0313.1 may act as a
      beneficial probiotic for the prevention and treatment of hyperglycemia and
      associated metabolic dysfunction.

PMID- 28765643
TI  - MiR-202-5p is a novel germ plasm-specific microRNA in zebrafish.
AB  - Gametogenesis is a complicated biological process by which sperm and egg are
      produced for genetic transmission between generations. In many animals, the
      germline is segregated from the somatic lineage in early embryonic development
      through the specification of primordial germ cells (PGCs), the precursors of
      gametes for reproduction and fertility. In some species, such as fruit fly and
      zebrafish, PGCs are determined by the maternally provided germ plasm which
      contains various RNAs and proteins. Here, we identified a germ plasm/PGC-specific
      microRNA miR-202-5p for the first time in zebrafish. MiR-202-5p was specifically
      expressed in gonad. In female, it was expressed and accumulated in oocytes during
      oogenesis. Quantitative reverse transcription PCR and whole mount in situ
      hybridization results indicated that miR-202-5p exhibited a typical germ plasm
      /PGC-specific expression pattern throughout embryogenesis, which was consistent
      with that of the PGC marker vasa, indicating that miR-202-5p was a component of
      germ plasm and a potential PGC marker in zebrafish. Our present study might be
      served as a foundation for further investigating the regulative roles of miRNAs
      in germ plasm formation and PGC development in zebrafish and other teleost.

PMID- 28765644
TI  - Lipid levels and new-onset diabetes in a hypertensive population: the China
      Stroke Primary Prevention Trial.
AB  - This study aimed to provide insights into the relationship between lipid levels
      and new-onset diabetes (NOD) in 14,864 Chinese hypertensive patients without
      diabetes (6056 men and 8808 women) aged 45-75 years from the China Stroke Primary
      Prevention Trial (CSPPT, led by Nanfang Hospital, Guangzhou, China). NOD (defined
      as fasting plasma glucose (FPG) >= 7.0 mmol/L at the end of study or self
      reported physician diagnosis of diabetes or self-reported use of hypoglycemic
      agents during follow-up) was analyzed using multivariate analysis. Follow-up was
      censored on August 24, 2014. Among the 14,864 subjects, 1615 developed NOD
      (10.9%, men = 10.8% and women = 10.9%). Increased triglycerides (TG) [odds ratio
      (OR) = 1.18; 95% confidence interval (CI): 1.13-1.25, P < 0.001], TG/HDL (OR =
      1.12; 95%CI: 1.08-1.17, P < 0.001), and decreased high density lipoprotein (HDL)
      (OR = 0.79; 95%CI: 0.67-0.93, P = 0.005) were associated with NOD, independently
      from age, gender, body mass index, clinical center, systolic blood pressure,
      diastolic blood pressure, FPG, smoking, and drinking. Compared to subjects with
      the methylenetetrahydrofolate reductase (MTHFR) 677 CC and TT genotypes, those
      with the CT genotype had a higher risk of NOD (OR = 1.54; 95%CI: 1.30-1.81, P for
      interaction = 0.044) in subjects with high TG. These results suggested that TG
      and TG/HDL were independent risk factors for NOD in this Chinese hypertensive
      population. HDL was a protective factor for NOD.

PMID- 28765645
TI  - Structure of the C-terminal domain of TRADD reveals a novel fold in the death
      domain superfamily.
AB  - The TNFR1-associated death domain protein (TRADD) is an intracellular adaptor
      protein involved in various signaling pathways, such as antiapoptosis. Its C
      terminal death domain (DD) is responsible for binding other DD-containing
      proteins including the p75 neurotrophin receptor (p75NTR). Here we present a
      solution structure of TRADD DD derived from high-resolution NMR spectroscopy. The
      TRADD DD comprises two super-secondary structures, an all-helix Greek key motif
      and a beta-hairpin motif flanked by two alpha helices, which make it unique among
      all known DD structures. The beta-hairpin motif is essential for TRADD DD to fold
      into a functional globular domain. The highly-charged surface suggests a critical
      role of electrostatic interactions in TRADD DD-mediated signaling. This novel
      structure represents a new class within the DD superfamily and provides a
      structural basis for studying homotypic DD interactions. NMR titration revealed a
      direct weak interaction between TRADD DD and p75NTR DD monomers. A binding site
      next to the p75NTR DD homodimerization interface indicates that TRADD DD
      recruitment to p75NTR requires separation of the p75NTR DD homodimer, explaining
      the mechanism of NGF-dependent activation of p75NTR-TRADD-mediated antiapoptotic
      pathway in breast cancer cell.

PMID- 28765646
TI  - Fabrication of a protein microarray by fluorous-fluorous interactions.
AB  - Fluorous-modified surfaces have emerged as a powerful tool for the immobilization
      of fluorous-tagged biomolecules based on their specificity and the strength of
      fluorous-fluorous interactions. To fabricate a fluorous-based protein microarray,
      we designed two strategies for site-specific modification of proteins with a
      fluorous tag: attaching the fluorous tag to the C-termini of expressed proteins
      by native chemical ligation (NCL) or to the Fc domain of antibodies through
      boronic acid (BA)-diol interactions. The perfluoro-tagged proteins could be
      easily purified by fluorous-functionalized magnetic nanoparticles (MNPs) and
      immobilized on a fluorous chip with minimal non-specific adsorption. Importantly,
      proteins immobilized on the solid support through non-covalent fluorous-fluorous
      interactions were sufficiently stable to withstand continuous washing. We believe
      that this fluorous-fluorous immobilization strategy will be a highly valuable
      tool in protein microarray fabrication.

PMID- 28765647
TI  - FGF2 cooperates with IL-17 to promote autoimmune inflammation.
AB  - IL-17 is a pro-inflammatory cytokine implicated a variety of autoimmune diseases.
      We have recently reported that FGF2 cooperates with IL-17 to protect intestinal
      epithelium during dextran sodium sulfate (DSS)-induced colitis. Here, we report a
      pathogenic role of the FGF2-IL-17 cooperation in the pathogenesis of autoimmune
      arthritis. Combined treatment with FGF2 and IL-17 synergistically induced ERK
      activation as well as the production of cytokines and chemokines in human
      synovial intimal resident fibroblast-like synoviocytes (FLS). Furthermore,
      ectopic expression of FGF2 in mouse joints potentiated IL-17-induced inflammatory
      cytokine and chemokine production in the tissue. In the collagen-induced
      arthritis (CIA) model, while ectopic expression of FGF2 in vivo exacerbated
      tissue inflammation and disease symptom in the wild-type controls, the effect was
      largely blunted in Il17a -/- mice. Taken together, our study suggests that FGF2
      cooperates with IL-17 to promote the pathogenesis of autoimmune arthritis by
      cooperating with IL-17 to induce inflammatory response.

PMID- 28765648
TI  - Role of Aortic Geometry on Stroke Propensity based on Simulations of Patient
      Specific Models.
AB  - Stroke is a life threatening event that is expected to more than double over the
      next 40 years. Atrial fibrillation (AF) has been reported as a strong independent
      risk factor for stroke. We have previously shown that a hemodynamic perturbation
      by AF or reduced cardiac output and cycle length may have a significant impact on
      clot trajectory and thus embolic stroke propensity through the left common
      carotid artery using an idealized aortic arch model. Here, we show the dependence
      of flow patterns and hence stroke propensity on geometry of patient-specific
      aortas. We performed computational fluid dynamics (CFD) simulations to determine
      the variations of AF-induced stroke propensity over various image-based patient
      dependent aorta models. The results demonstrated that curvature pattern of aorta
      can play a determinant role in AF-induced stroke propensity alteration.
      Specifically, it was shown that the hemodynamic perturbation by AF considered led
      to substantial increase in stroke propensity (i.e., 2.5~3.8 fold elevation) for
      lower curvature angle <90 degrees  while the changes in stroke propensity by AF
      are negligible for higher curvature angle >90 degrees . The present simulations
      suggest that aortic arch curvature is an important risk factor for embolic stroke
      which should be tested in future clinical trials.

PMID- 28765649
TI  - Hyperbolic-polaritons-enabled dark-field lens for sensitive detection.
AB  - Sensitive detection of features in a nanostructure may sometimes be puzzled in
      the presence of significant background noise. In this regard, background
      suppression and super-resolution are substantively important for detecting weakly
      scattering nanoscale features. Here, we present a lens design, termed hyperbolic
      polaritons-enabled dark-field lens (HPEDL), which has the ability to accomplish
      straightforward sensitive detection. This HPEDL structure consists of type I and
      type II hyperbolic media that support high-k field waves via hyperbolic
      polaritons (HPs). We show that the cone-like characteristics of the HPs could be
      manipulated while the influence of the low-k field waves would be removed.
      Numerical simulations demonstrate that this proposed structure can successfully
      realize straightforward sensitive detection by modifying its thickness under the
      phase compensation condition. Besides, the minimum resolvable length and angular
      dependent performance for sensitive detection are also demonstrated by
      simulations. Remarkably, these findings are very promising for propelling
      nanophotonics technologies and constitute a further important step towards
      practical applications of optical microscopy.

PMID- 28765650
TI  - Implication of REDD1 in the activation of inflammatory pathways.
AB  - In response to endotoxemia, the organism triggers an inflammatory response, and
      the visceral adipose tissue represents a major source of proinflammatory
      cytokines. The regulation of inflammation response in the adipose tissue is thus
      of crucial importance. We demonstrated that Regulated in development and DNA
      damage response-1 (REDD1) is involved in inflammation. REDD1 expression was
      increased in response to lipopolysaccharide (LPS) in bone marrow derived
      macrophages (BMDM) and in epidydimal adipose tissue. Loss of REDD1 protected the
      development of inflammation, since the expression of proinflammatory cytokines
      (TNFalpha, IL-6, IL-1beta) was decreased in adipose tissue of REDD1-/- mice
      injected with LPS compared to wild-type mice. This decrease was associated with
      an inhibition of the activation of p38MAPK, JNK, NF-kappaB and NLRP3 inflammasome
      leading to a reduction of IL-1beta secretion in response to LPS and ATP in REDD1
      /- BMDM. Although REDD1 is an inhibitor of mTORC1, loss of REDD1 decreased
      inflammation independently of mTORC1 activation but more likely through oxidative
      stress regulation. Absence of REDD1 decreases ROS associated with a dysregulation
      of Nox-1 and GPx3 expression. Absence of REDD1 in macrophages decreases the
      development of insulin resistance in adipocyte-macrophage coculture. Altogether,
      REDD1 appears to be a key player in the control of inflammation.

PMID- 28765652
TI  - Hardening of shear band in metallic glass.
AB  - Strain hardening, originating from defects such as the dislocation, avails
      conventional metals of high engineering reliability in applications. However, the
      hardenability of metallic glass is a long-standing concern due to the lack of
      similar defects. In this work, we carefully examine the stress-strain
      relationship in three bulk monolithic metallic glasses. The results show that
      hardening is surely available in metallic glasses if the effective load-bearing
      area is considered instantly. The hardening is proposed to result from the
      remelting and ensuing solidification of the shear-band material under a
      hydrostatic pressure imposed by the normal stress during the shear banding event.
      This applied-pressure quenching densifies the metallic glass by discharging the
      free volume. On the other hand, as validated by molecular dynamics simulations,
      the pressure promotes the icosahedral short-range order. The densification and
      icosahedral clusters both contribute to the increase of the shear strength and
      therefore the hardening in metallic glasses.

PMID- 28765651
TI  - CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan
      recognition.
AB  - Agonist interaction with Toll-like receptors (TLRs) induces T cell-mediated
      immunity, which is effective against intracellular pathogens. Consequently, TLR
      agonists are being tried as immunomodulatory agents. The lectin ArtinM targets
      TLR2 N-glycans on macrophages, induces cytokines production, and promotes T
      helper-1 immunity, a process that culminates in resistance to several parasitic
      and fungal infections in vivo. Because co-receptors influence agonist binding to
      TLRs, we investigated whether CD14 is required for macrophage activation induced
      by ArtinM. Macrophages from wild-type mice stimulated by ArtinM not only produced
      cytokines but also had the following activation profile: (i) expression of M1
      polarization markers; (ii) nitrite oxide production; (iii) cellular migration;
      (iv) enhanced phagocytic and fungicide activity; (v) modulation of TLR2
      expression; and (vi) activation of NF-kappaB pathway. This activation profile
      induced by ArtinM was evaluated in macrophages lacking CD14 that showed none of
      the ArtinM effects. We demonstrated by immunoprecipitation and sugar inhibition
      assays the physical interaction of ArtinM, TLR2, and CD14, which depends on
      recognition of the trimannoside that constitutes the core of N-glycans. Thus, our
      study showed that CD14 is critical for ArtinM-induced macrophage activation,
      providing fundamental insight into the design of anti-infective therapies based
      on carbohydrate recognition.

PMID- 28765653
TI  - [Adaptation and validation of five scales to measure determinants of binge
      drinking in adolescents].
AB  - BACKGROUND: The aim of this study was to validate five scales, based on a
      theoretical framework for the adoption of behaviours, designed to assess the
      determinants in binge drinking in adolescents, namely: attitude, social influence
      (model, norm and pressure) and self-efficacy. METHODS: Observational, cross
      sectional and multicentre study. Through convenience sampling, 397 adolescents
      between 15 to 18 years old enrolled in secondary schools in Seville and Huelva
      were included. After translation and review of the original instrument by a panel
      of experts, a questionnaire was obtained in Spanish that was administered to a
      pilot sample to assess comprehensibility and, subsequently, the participants
      completed the five scales to check the structural validity (factor analysis and
      reliability) and construct validity. RESULTS: On the five scales, the first
      factor explained at least 28% of the variance and the total variance explained
      was always greater than 60%. After rotation, all items had weights >0.40 for the
      factor to which they belonged. Cronbach's alpha ranged from 0.62 to 0.91.
      Spearman's coefficient was lower than 0.7 when correlating the sub-dimensions of
      the scales, except on the self-efficacy scale, assuming multidimensionality with
      certain limitations. CONCLUSIONS: Five scales are presented with indications of
      reliability and validity, their items reflect the theoretical frame of reference
      and can evaluate the determinants of binge drinking. In the future, validation
      could be continued to determine its reproducibility, its criterion validity with
      a "gold standard" or objective measure. Key words. Adolescents. Health behaviour.
      Binge drinking. RISK FACTORS: Validation studies.

PMID- 28765654
TI  - [Analysis of clinical safety in the units of Allergy of the Valencian Community].
AB  - The introduction of new diagnostic and therapeutic procedures involving allergen
      exposure may increase the risk of allergic reactions. We designed and distributed
      an anonymous questionnaire among the allergy units of the Valencian Community in
      order to collect information on measures to ensure clinical safety. Twelve
      hospital outpatient clinics and 8 ambulatory care centres reported similar
      patterns of activities, including the use of critical care units, emergency rooms
      or day hospitals for higher risk techniques. The provision of security-related
      instruments is broader in hospital outpatient clinics and included: oxygen
      (91.7%), pulse oximeter (75.0%) or vital signs monitor (8.3%), resuscitation
      material (91.7%) and defibrillator (83.3%). The response time for emergencies is
      set in 50% of clinics. The resuscitation material is systematically reviewed and
      informed consent signed. Security is more limited in ambulatory care centres. It
      is necessary to set down the conditions for clinical safety in allergology. Key
      words. Allergy. Ambulatory care. Clinical safety. Health services. Hospital
      outpatient clinic.

PMID- 28765655
TI  - [Social cognition in schizophrenia: the relevance of early detection and
      intervention].

PMID- 28765656
TI  - [Comparison of clinical features and diagnosis between the A and B subgroups of
      respiratory syncytial virus.]
AB  - BACKGROUND: Lower respiratory tract infection by respiratory syncytial virus
      (RSV) is the most frequent cause of admission in children under 2 years old. The
      RSV subgroups A and B may circulate simultaneously. We aimed to determine whether
      clinical differences exist between RSV subgroups A and B. Additionally, we tested
      the sensitivity of the rapid antigen detection test (RADT) based on
      immunochromatography in diagnosing subgroups A and B, taking the polymerase chain
      reaction assay (RT-PCR) as reference. METHODS: A retrospective observational
      study was performed in a tertiary hospital from October 2013 to March 2014.
      Clinical records and analytical variables of all children under 5 admitted with
      lower respiratory tract infection and RT-PCR positive for RSV in nasal lavage
      were consulted. Previously, the RADT for RSV had been performed from the same
      sample. RESULTS: A total of 198 children under 5 were diagnosed with RSV by RT
      PCR: 55 (28%) were RSV-A, 132 (67%) RSV-B and 11 (5%) were positive for both
      subgroups. No differences were observed between subgroups in medical history,
      symptoms, radiological and analytical findings, and severity. The sensitivity of
      RADT for RSV was 52%, higher for RSV-A (69%) than for RSV-B (44%, p=0.001).
      CONCLUSIONS: The two RSV subgroups were indistinguishable in symptoms and
      prognosis. The sensitivity of RADT compared to RT-PCR was low and limits its
      usefulness for clinical decision-making. Key words. Respiratory syncytial virus.
      RSV subgroups. Rapid antigen detection test. Reverse transcription polymerase
      chain reaction.

PMID- 28765657
TI  - [Knowledge and willingness to perform basic life support by local police
      officers].
AB  - BACKGROUND: To determine the knowledge and willingness of local police officers
      (PO) to perform cardiopulmonary resuscitation (CPR), as well as to explore the
      association between CPR training and these variables. METHODS: Cross-sectional
      study with a sample of 390 PO from Asturias (Spain). An anonymous questionnaire
      was used to measure nine basic aspects of CPR from the European Resuscitation
      Council and four indicators of attitude towards performing CPR in a real context.
      Information on CPR training and its periodicity was also collected, as well as
      basic socio-demographic and occupational variables. RESULTS: Lack of CPR training
      was seen in 19.7% of PO, and 36.4% had received such training more than two years
      ago. Almost one out of four PO had performed at least one CPR in a real situation
      (24.1%), of which 9.6% had not been trained. The least remembered aspects of CPR
      were depth (11%) and frequency of chest compressions (24.4%). Only 49.7% of the
      agents felt sufficiently prepared to perform a CPR. Knowledge and disposition
      were significantly associated with having received training with a periodicity of
      less than two years. CONCLUSIONS: Given that PO are frequently first responders
      in situations of out-of-hospital cardiorespiratory arrest, specific training in
      CPR should be mandatory and periodic, with at least one course every two years.
      It would be interesting to determine which didactic instrumentation is most
      efficient for disseminating these training courses among police officers. Key
      words. Police. Cardiopulmonary resuscitation. Out-of-hospital cardiac arrest;
      attitude. Emergencies.

PMID- 28765658
TI  - [Diabetes in emergency services: evaluation of monitoring and installed
      treatments].

PMID- 28765659
TI  - [Empathy, social cognition and subjective quality of life in schizophrenia].
AB  - BACKGROUND: People diagnosed with schizophrenia present empathy deficits that
      have been related to their poor psychosocial functioning. The objectives were: 1)
      analyse the relation between empathy, social cognition and quality of life in
      subjects diagnosed with schizophrenia and other psychotic disorders; 2) eva!luate
      these variables according to the severity of the features. METHODS: Forty-one
      patients, divided into two groups according to the level of severity, were
      included. A battery of tests was applied: Interpersonal Reactivi!ty Index (IRI),
      GEOPTE scale of social cognition for psychosis, World Health Organization Quality
      of Life Assessment: Brief Version (WHOQOL-BREF), Clini!cal Global Impression
      scale (CGI), Scale for the As!sessment of Positive Symptoms (SAPS) and Negative
      Symptoms (SANS). RESULTS: There was a direct relationship between per!sonal
      anxiety and fantasy sub-scales of the IRI and the GEOPTE scale, and an inverse
      relationship with seve!ral dimensions of quality of life of the WHOQOL-BREF. The
      GEOPTE scale had an inverse relation with all the dimensions of quality of life
      evaluated. The mildly sick group obtained scores that were significantly lower in
      fantasy (15.44 vs. 20.12; p=0.001) and significantly hig!her in psychological
      health (58.63 vs. 45.40; p=0.017) and environment (67.00 vs. 53.68; p=0.006).
      CONCLUSIONS: A relationship is found between empathy, social condition and
      perceived quality of life in people diagnosed with schizophrenia on programs of
      psycho-social rehabilitation. Similarly, the existence of relevant differences in
      these variables according to the level of severity of the clinical features is
      underscored.

PMID- 28765660
TI  - [Changes in quality of life in patients undergoing bariatric surgery following 24
      months: comparison between gastric bypass and tubular vertical gastrectomy].
AB  - BACKGROUND: Bariatric surgery has become the procedure of choice to deal with
      morbid and super-morbid obesity, with the greatest chance of success. The
      objectives of this study were: a) to analyse the evolution of the percentage of
      excess BMI lost (PEBMIL) and quality of life in the medium and long term after
      bariatric surgery; b) to evaluate the differences in PEBMIL and quality of life
      according to the surgical technique performed; and c) examine the relationship
      between PEBMIL and quality of life. METHODS: One hundred and ninety-one subjects
      participated in the present study, undergoing bariatric surgery with follow-up at
      12 and 24 months after surgery. The SF-36 and OP-53 questionnaires were
      administered to assess the quality of life after surgery. RESULTS: There was a
      statistically significant reduction in the percentage of excess BMI lost at 12
      and 24 months; and a significant improvement in quality of life at 12 months,
      which remained stable at 24 months for most variables. Taking into account the
      surgical technique, those undergoing gastric bypass surgery show a greater loss
      of PEBMIL at 12 and 24 months, and significant improvement at one year of
      evaluation in most of the dimensions that measure quality of life with respect to
      the tubular vertical gastrectomy technique. CONCLUSION: Bariatric surgery is
      effective in reducing the excess of BMI lost and significantly improving the
      quality of life of morbidly obese patients in the long term. Key words. Bariatric
      surgery. Quality of life. Morbid obesity.

PMID- 28765661
TI  - [Factors associated with blood loss during precipitate labor].
AB  - BACKGROUND: Precipitate labour is related to the appearance of postpartum
      haemorrhage due to posterior uterine atony. However, preventive measures that may
      be effective in reducing blood loss in this type of delivery are still unknown.
      Therefore, the objective of this study was to determine the risk factors
      associated with blood loss produced in precipitate labour. METHODS: This was an
      observational, analytical retrospective cohort study based on a total sample of
      742 women with vaginal delivery whose duration was less than 180 minutes, during
      the period 2010-2014. Dead foetus antepartum gestations, twin gestations and
      labour induction were excluded from the analysis. The main outcome variable was
      intrapartum blood loss. RESULTS: By making use of multivariate analysis, the risk
      factors independently associated with higher blood loss (g/dL) during precipitate
      labour were nulliparity (0.38; p<0.001), higher antepartum haemoglobin levels
      (0.23; p<0.001), higher gestational age (0.06; p<0.001), manual removal of the
      placenta (0.92; p=0.004) and the use of episiotomy (0.34; p<0.001). Performing
      active management emerges as a protective factor against increased blood loss (
      0.23; p<0.001). The average loss of haemoglobin was 1.0 g/dL (standard deviation
      =0.92). CONCLUSION: The restriction in the practice of episiotomy and the use of
      active management can therefore be established as key measures that professionals
      can modify in order to reduce blood loss during precipitate labour and to improve
      these mothers' postpartum period. Key words. Haemoglobin. Precipitate labour.
      RISK FACTORS: 

PMID- 28765662
TI  - [Retrorectal cystic hamartoma (tailgut cyst): an uncommon cause of recurrent
      abdominal pain.]
AB  - Retrorectal cystic hamartomas are rare congenital lesions that arise from
      aberrant remnants of the postanal gut. Most of them appear as asymptomatic
      lesions in middle-aged women but they can manifest with nonspecific symptoms such
      as abdominal or pelvic pain, constipation or diarrhoea, genitourinary symptoms,
      etc. Due to their anatomical position and variable presentation these lesions are
      often misdiagnosed. Complications include infection and malignant transformation,
      which is the reason why surgical treatment is always indicated. We report a case
      of a woman with recurrent episodes of abdominal pain that lasted for many years
      and increased progressively, conditioning her daily life activities. Image
      studies showed a non-complicated retrorectal cystic hamartoma. Complete surgical
      excision was achieved and the patient remains asymptomatic nowadays. Key words.
      Retrorectal cystic hamartoma. Abdominal pain.

PMID- 28765663
TI  - [Highly aggresive pulmonary epithelioid hemangioendothelioma: a case report].
AB  - Pulmonary epithelioid hemangioendothelioma is an uncommon neoplastic disease of
      endothelial origin, with an incidence inferior to one in a million. It usually
      behaves as a low-grade malignancy; nevertheless, a few cases have been described
      in which this tumour manifests a highly aggressive behavior, spreading throughout
      the organism. We report the case of a 77-year-old woman who was diagnosed with
      metastatic pulmonary epithelioid hemangioendothelioma with severe symptoms,
      requiring urgent treatment to palliate them. Key words. Epithelioid
      hemangioendothelioma. Lung.

PMID- 28765664
TI  - [Identification of shortcomings in clinical care of asthma in Spain. Results of
      the OPTIMA_GEMA survey].

PMID- 28765665
TI  - [Chronic patient activation and their relationship with health professionals in
      Andalusia].
AB  - BACKGROUND: To evaluate the (inter)relation between chronic patient activation
      and its relationship with health professionals in Andalusia. METHODS: Descriptive
      and quantitative study involving 258 chronic patients from the School of
      Patients, contacted by email. One hundred and forty-two answered the Patient
      Activation Measurement (PAM) and the chronic patient's experience (IEXPAC)
      questionnaires. Statistical analyses included correlation study and comparison of
      means. RESULTS: The mean of Patient Activation Measurement was 87 points (scale
      from 0 to 100) and IEXPAC scale was 5.3 (scale from 0 to 10), with a directly
      proportional relation between variables. Males and participants belonging to
      patients' associations had higher levels of activation. The relationship with
      health professionals was better among patients with primary education and with
      <10 years of chronic disease. In general, medical staff received better
      evaluation, yet nurses were considered more prone to encouraging relationships
      among patients. The dimensions with higher impact on patient activation were
      inter-professional coordination and the attention paid to treatment and
      medication. Feeling confident to communicate one's concerns had more impact on
      IEXPAC scale. CONCLUSIONS: The correlation observed between patient activation
      and its relationship with health professionals leads to the need to improve the
      involvement and self-management of chronic patients, as well as to strengthen
      improved professional coordination and patient-staff communication.

PMID- 28765666
TI  - [In case of an adverse event don't forget to say sorry].
AB  - BACKGROUND: Disclosing information to a patient who is a victim of an adverse
      event (AE) presents some particularities depending on the legal framework in the
      country where the AE occurred. The aim of this study is to identify the limits
      and conditions when apologizing to a patient who has suffered an AE. METHODS: A
      consensus conference involving 26 professionals from different autonomous
      communities, institutions, and profiles (health, insurance, inspection, academic)
      with accredited experience in patient safety management systems and criminal law.
      RESULTS: Open disclosure should include an apology expressed in neutral terms
      (showing empathy and regret for what has happened) without the informant being
      identified as responsible for the damage, blaming third parties, or offering
      compensation on behalf of the insurance company. The professional who feels most
      directly involved in the incident is usually the least likely to report it and
      apologise. The informant profile must conform to the type and severity of the AE.
      The rules and conditions of liability insurance advise against providing specific
      information on the amount of compensation. CONCLUSIONS: The apology should be
      offered in terms of the regulatory framework in force in each country. In Spain,
      an appropriate response of empathy for the patient is warranted, expressing
      regret for what happened (apologising), which can facilitate the relationship
      with the patient, mitigate their mistrust, and reduce the number of disputes.

PMID- 28765667
TI  - The relationship between physical activity and work ability - A cross-sectional
      study of teachers.
AB  - OBJECTIVES: To assess relationship between physical activity (PA) and perceived
      work ability amongst teachers from the Upper Silesia, Poland. MATERIAL AND
      METHODS: The study involved 171 teachers (129 women, 42 men) of primary and
      secondary schools of the Upper Silesia, Poland. Physical education teachers were
      excluded from the study. The level of PA was estimated using the International
      Physical Activity Questionnaire short version, and perceived work ability was
      estimated using Work Ability Index (WAI). RESULTS: Male teachers had
      significantly higher levels of vigorous-intensity PA, moderateintensity PA, and
      total weekly PA than female teachers. The recommendations of the World Health
      Organization (WHO) met 46% of studied women and 74% of men. Work ability did not
      differ between male and female teachers. Work ability was related to age, body
      mass index (BMI), and PA (vigorous-intensity PA, moderate-intensity PA, total
      weekly PA). The female teachers with excellent or good WAI had significantly
      higher levels of vigorous-intensity PA, moderate-intensity PA and total weekly PA
      than female teachers with moderate or poor WAI. CONCLUSIONS: The teachers
      involving in high or moderate intensity PA could improve their work ability.
      Further studies should focus on relation between physical activity and work
      ability among teachers of various age and seniority, from both, urban and rural
      schools. Int J Occup Med Environ Health 2018;31(1):1-9.

PMID- 28765668
TI  - The Year of the Brave Rooster.

PMID- 28765669
TI  - Application to skin physiology using optical coherence tomography.
AB  - Background and aims: The sweat glands and peripheral vessels beneath the skin
      surface act as minute organs governed by the skin sympathetic nerves and have
      important physiological functions for body temperature control and nutrition
      support along with maintenance of a peripheral organization. Dynamics of the
      mental sweating of sweat glands and the peripheral vessels reflect the activity
      of a sympathetic nerve. The purpose of this paper is to study the dynamic
      observation and analysis of sweat glands and a peripheral vessels by optical
      coherence tomography (OCT). Materials and Methods: In the dynamic analysis of
      mental sweating of sweat glands, after confirmation of the resting state of the
      volunteer, mental stress was applied in the form of unpleasant sound for 0.5 sec;
      piled-up en-face OCT images of sweat glands were then obtained time-sequentially,
      with the frame-spacing of 3.3 sec. A swept-source (SS) OCT was used for in vivo
      en-face OCT of a group of sweat glands on the subject's fingertip. Furthermore,
      we conducted in vivo dynamic analysis in response to external mental stress of a
      peripheral vessel in the second joint of the subject's third finger using 1.3-um
      SS OCT. Results: We analyzed time variation in the amount of excess sweat
      produced by a group of sweat glands and found a large difference in the amount of
      sweat stored by each sweat gland in the spiral lumen. Mental stress was also
      shown to cause the small artery of the finger to contract, reducing blood flow.
      In particular, the thickness of the tunica media of the small artery changed
      abruptly in response to the sound stress, increasing and then decreasing so that
      the artery contracted and expanded, respectively. Conclusions: Dynamic analysis
      of mental sweating in the eccrine sweat glands and changes in peripheral vessels
      was performed using time-sequential OCT imaging. For mental sweating, time
      variation in the amount of excess sweat produced could be simultaneously
      evaluated for a few tens of eccrine sweat glands. Furthermore, we performed the
      dynamic analysis of a peripheral vessel in a human finger in response to external
      mental stress and found that the small artery contracted and expanded in response
      to sound stress while continuing to pulse in synchronization with the heartbeat.
      These studies have the potential for establishing new knowledge about skin
      physiology.

PMID- 28765670
TI  - Microleakage in Class V Composite Restorations after Desensitizing Surface
      Treatment with Er:YAG and CO2 Lasers.
AB  - Aims: Glutaraldehyde, CO2 and Er:YAG lasers can be used for treatment of dentin
      hypersensitivity. However, their application may have adverse effects on the
      clinical service of restorations. This study aimed to assess the microleakage in
      composite restorations following surface treatment with Glutaraldehyde
      desensitizer, CO2 and Er:YAG laser irradiation for treatment of dentin
      hypersensitivity. Materials and methods: This experimental study was conducted on
      60 extracted sound human teeth. Class V cavities were prepared measuring 3*3 mm
      using a diamond bur. Specimens were randomly divided into 4 groups of 15. Group
      one:no surface treatment, Group two:applying Glutaraldehyde desensitizer, Groups
      of three and four were irradiated with CO2 and Er:YAG lasers, respectively.
      Surfaces were restored with bonding agent (Single Bond 2, 3M, USA) and Z250
      composite (3M, USA). Specimens were thermocycled and immersed in 1% methylene
      blue solution for 24 hours. Microleakage scores were assessed under a
      stereomicroscope at *20 magnification. Data were analyzed using SPSS and the
      Kruskal Wallis test (P=0.05). Results: There was no significant difference
      between microleakage of groups in enamel margins (P=0.694). The difference in
      microleakage at the dentin margin was significant between groups (P=0.018).
      Conclusions: Application of Glutaraldehyde-desensitizer and CO2 laser irradiation
      of surfaces prior to composite restoration do not increase microleakage at the
      enamel or dentin margins but tooth surface treatment with Er:YAG laser
      significantly increased the microleakage at the dentin margins.

PMID- 28765671
TI  - Evaluation of the Diode laser (810nm, 980 nm) on color change of teeth after
      external bleaching.
AB  - Subject and aim: The aim of this study was to evaluate the efficiency of diode
      laser-activated bleaching systems for color change of teeth. Materials & Methods:
      40 premolars with intact enamel surfaces were selected for five external
      bleaching protocols (n=8). Two different wavelengths of diode laser (810 and 980
      nm) with two different hydrogen peroxide concentrations (30% and 46%) were
      selected for laser bleaching. Group 1 received bleaching (Heydent- Germany) with
      a 810 nm diode laser; Group 2 received bleaching (Heydent- Germany) with a 980 nm
      diode laser; Group 3 received bleaching (laser white*20- Biolase) with a 810 nm
      diode laser; Group 4 received bleaching (laser white*20- Biolase) with a 980 nm
      diode laser, with an output power of 1.5 W, in continuous wave (cw) mode for each
      irradiation. Group 5 as control group received 40% hydrogen peroxide (Opalescence
      Boost, Ultradent-USA) with no light activation. The color of teeth was scored at
      baseline and 1 week after bleaching with spectrophotometer. Color change data on
      the CIEL*a*b* system were analyzed statistically by the one-way ANOVA and Tukey's
      HSD test. Results: All the bleaching techniques resulted in shade change.
      According to DeltaE values, all techniques were effective to bleach the teeth
      (DeltaE >= 3). Statistically significant differences were detected among
      bleaching protocols (p=0.06). Regarding shade change values expressed as DeltaL*,
      Deltaa*, Deltab*, DeltaE*, laser bleached groups were no statistically different
      with each other (p>0.05). Conclusion: Bleaching with different wavelengths of
      diode laser resulted in the same results.

PMID- 28765672
TI  - Analysis of Thermally Denatured Depth in Laser Vaporization for Benign Prostatic
      Hyperplasia using a Simulation of Light Propagation and Heat Transfer (secondary
      publication).
AB  - Background and Aims: Laser vaporization of the prostate is expected as a less
      invasive treatment for benign prostatic hyperplasia (BPH), via the photothermal
      effect. In order to develop safer and more effective laser vaporization of the
      prostate, it is essential to set optimal irradiation parameters based on
      quantitative evaluation of temperature distribution and thermally denatured depth
      in prostate tissue. Method: A simulation model was therefore devised with light
      propagation and heat transfer calculation, and the vaporized and thermally
      denatured depths were estimated by the simulation model. Results: The results of
      the simulation were compared with those of an ex vivo experiment and clinical
      trial. Based on the accumulated data, the vaporized depth strongly depended on
      the distance between the optical fiber and the prostate tissue, and it was
      suggested that contact laser irradiation could vaporize the prostate tissue most
      effectively. Additionally, it was suggested by analyzing thermally denatured
      depth comprehensively that laser irradiation at the distance of 3 mm between the
      optical fiber and the prostate tissue was useful for hemostasis. Conclusions:
      This study enabled quantitative and reproducible analysis of laser vaporization
      for BPH and will play a role in clarification of the safety and efficacy of this
      treatment.

PMID- 28765673
TI  - Laser biostimulation effects on invertebral disks: histological evidence on intra
      observer samples. Retrospective double-blind study.
AB  - Background and aims: The intervertebral disk degeneration is a pathological
      process determined by a decrease of mucopolysaccharides in the nucleus pulposus
      with the consequent dehydration and degeneration of the elastic fibers in the
      annulus fibrosus of the disk. The laser is a therapeutic tool that has, on the
      treated tissues, biostimulation effects with an increase of oxidative
      phosphorylation and production of ATP with an acceleration of the
      mucopolysaccharides synthesis with a consequent rehydration, biostimulation and
      production of new elastic fibers. The goal of this project is studying whether
      the laser stimulation may treat degenerated intervertebral disks. Materials and
      methods: 60 subjects with the same anthropometric parameters were selected and
      divided into two randomized groups. 30 subjects underwent laser stimulation,
      whereas 30 underwent placebo. All 60 subjects underwent a discectomy surgery and
      the intraoperative findings were examined in a lab, studying the positivity of
      the PAS reaction and the presence of potential newly formed elastic fibers.
      Results: It has been shown a higher number of mucopolysaccharides and young newly
      formed elastic fibers in the group that was treated with laser irradiation with a
      statistically significant difference, compared to the placebo group (p< 0.0001).
      Conclusions: Laser biostimulation can be an effective strategy in the therapy of
      the invertebral disks.

PMID- 28765674
TI  - A comparative evaluation of retention of pit and fissure sealants placed with
      conventional acid etching and Er,Cr:YSGG laser etching: A randomised controlled
      trial.
AB  - : Aim: The aim of this study was to compare the retention rates of sealant placed
      either with conventional acid etching or Er,Cr:YSGG laser pretreatment of enamel
      surface. Materials and methods: This is a prospective, single blind randomised
      controlled clinical trial enrolling 200 permanent first molars in 50 patients,
      aged 6-12 years for sealant placement. Study followed split mouth design where
      each side of the arch was randomly allocated to the two treatment group. Group
      A(Acid etch group): 37 % phosphoric acid (Scotchbond, 3M ESPE, Seefeld, Germany)
      was applied for 15 seconds, rinsed with water for 20 seconds and then air-dried
      using air spray. Group L(Laser etch group): Fissures were prepared with an
      Er,Cr:YSGG laser system (Waterlase, BIOLASE Technology, San Clemente, CA, USA)
      emitting photons at a wavelength of 2.78 um. Laser irradiation at 1.5 W (60% air
      and 40% water), in a noncontact mode, with a repetition rate of 20 Hz for
      10seconds was used. Pit and fissure sealant (3M ESPE, Clinpro) was applied and
      cured for 20 seconds. One blinded, calibrated examiner, who was unaware of which
      preparation method has been used and who was not involved in the treatment
      procedures, evaluated the sealant at baseline and at 3, 6, 9 and 12 month follow
      up visits. Results: It was observed that overall retention rate in group A was
      slightly higher as compared to group L at all time periods, however, the
      difference was statistically non-significant (p-value>0.05). CONCLUSION:
      Er,Cr:YSGG laser etching is comparable to acid etching in terms of retention and
      patient acceptability.

PMID- 28765675
TI  - Effect of antimicrobial photodynamic therapy using rose bengal and blue light
      emitting diode on Porphyromonas gingivalis in vitro: Influence of oxygen during
      treatment.
AB  - Aims: A combination of rose bengal (RB) and blue LED (BL) has emerged as a new
      technical modality for antimicrobial photodynamic therapy (a-PDT). The purpose of
      this study was to clarify the influence of oxygen on the antimicrobial effect of
      RB + BL treatment on Porphyromonas gingivalis in vitro.Materials and Methods:P.
      gingivalis cells were treated with RB, BL (450-470 nm; 1 W/cm2, 5 s), or RB + BL
      under anaerobic/aerobic conditions. Cells were incubated anaerobically, and the
      cell density (OD600 nm) was measured after 6-48 h. Additionally, cells were
      cultured anaerobically on blood agar plates for 9 days, and the resulting
      colonies were observed. Bacterial growth within 1 h of aerobic RB + BL treatment
      was examined, and RNA degradation due to anaerobic/aerobic RB + BL treatment was
      measured after 3 h of culture. Results: Under anaerobic conditions, RB + BL
      significantly suppressed bacterial growth after 18 h; however, the growth after
      48 h and the number of colonies after 9 days were similar to those of the
      untreated control. RNA degradation in the anaerobic-treatment group was not
      significantly different from that in the control. Under aerobic conditions, RB +
      BL immediately affected bacterial growth and completely inhibited growth for up
      to 48 h. Few colonies were detected even after 9 days of culture, and RNA was
      completely degraded. Conclusions: Unlike the bacteriostatic effect of anaerobic
      treatment, aerobic RB + BL treatment may have a bactericidal action via a-PDT
      effect, resulting in the destruction of RNA and bacterial cells within a short
      period.

PMID- 28765676
TI  - Fate of the untreated anterior cruciate ligament-injured knee.

PMID- 28765678
TI  - Factors Related to Acute Anxiety and Depression in Inpatients with Accidental
      Orthopedic Injuries.
AB  - BACKGROUND: Those injured in accidents commonly have strong emotional reactions
      to their situation. However, despite the large number of patients who are
      admitted to general hospitals each year for orthopedic injuries due to an
      accident, research focusing on psychological disorders due to these injuries is
      lacking. OBJECTIVE: To investigate the presentation and factors related to
      depression and acute anxiety among inpatients being treated for injury on a
      Trauma Orthopedics Unit. METHODS: 323 patients with orthopedic trauma were
      evaluated using the Injury Severity Score (ISS), Hamilton Anxiety Scale (HAMA)
      and Hamilton Depression Scale (HAMD). RESULTS: In this study, a total of 323
      inpatients (213 males and 110 females) had a mean (sd) age of 44.3 (13.2) years
      old. Mean (sd) time in the hospital was 11.1 (5.7) days with a range of 2 to 40
      days. Among these patients, 299 had mild trauma, 20 had moderate trauma, and 4
      had severe trauma. Patients had a mean (sd) score of 8.1 (4.9) with a range of 1
      to 38. The top three most reported symptoms from the HAMA were sleep disorder,
      gastrointestinal symptoms and anxiety. The top three most reported symptoms from
      the HAMD were sleep disorder, depression and anxiety. Non-conditional logistic
      regression analysis showed that being female (anxiety: OR=2.738, 95%CI=1.511
      4.962; depression: OR=2.622, 95%CI=1.504-4.570) and duration of hospitalization
      (anxiety: OR=1.091, 95%CI=1.040-1.145; depression: OR=1.093, 95%CI=1.044-1.144)
      were risk factors for anxiety and depression among these orthopedic trauma
      patients. CONCLUSION: The main acute symptoms of anxiety and depression in these
      orthopedic trauma inpatients were sleep disorder, gastrointestinal symptoms,
      anxious mood and depressed mood. Female patients had stronger emotional reactions
      to injuries than males. Persistent anxiety and depression symptoms were
      associated with the duration of hospitalization. All these suggest the need for
      early psychological assessment and intervention for orthopedic trauma inpatients.

PMID- 28765677
TI  - Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic
      Stimulation Treatment for Patients with Schizophrenia: A Systematic Review.
AB  - BACKGROUND: Negative symptoms are one of the most difficult areas in the
      treatment of schizophrenia because antipsychotics are often less effective
      towards them. Repetitive transcranial magnetic stimulation (rTMS) is a new
      technique for cerebral cortex stimulation and is believed to be a safe and
      promising method for the treatment of mental disorders. As the clinical research
      and new treatment models have increased in recent years, the efficacy towards
      negative symptoms and safety evaluation of rTMS treatment should also be updated.
      AIMS: To explore the efficacy and safety of rTMS in the treatment of negative
      symptoms for patients with schizophrenia. METHODS: We searched for relevant
      controlled clinical trials from the following databases: PubMed, EMBASE, the
      Cochrane Library, EBSCO, Web of Science, China National Knowledge Infrastructure
      (CNKI), VIP, Wanfang Data, SINOMED, and Airiti Library. The retrieval time went
      up to January 2, 2017. The research literature was screened according to the
      predefined inclusion and exclusion criteria. After data extraction, statistical
      analysis was conducted by using RevMan 5.3 and Stata 14. Quality evaluation was
      done on the included research articles. The Cochrane risk of bias assessment tool
      was adopted for assessing risk of bias. The GRADE (Grades of Recommendation,
      Assessment, Development, and Evaluation) system recommendation grading method was
      used as the reference standard. RESULTS: A total of 3500 articles were retrieved.
      In the end, there were 29 articles included in the metaanalysis with a total
      sample size of 1440. After the meta-analysis, it was found that the use of
      antipsychotic treatment combined with rTMS could improve the negative symptoms of
      patients (SMD=-0.40, 95% CI= -0.62~-0.18). Based on the bias of the efficacy
      evaluation assessed by the Cochrane risk of bias assessment tool, there were 6
      studies rated as having "high risk of bias" and the rest were rated as "unable to
      determine". According to the assessment, development and evaluation criteria of
      the GRADE classification, the evidence quality for the efficacy evaluation index
      was "moderate". The acceptability of rTMS treatment was better (RR= 0.75, 95% CI=
      0.49~1.15, based on the 1492 samples from the 28 studies), however, the patients
      who received the rTMS treatment had a higher rate of mild adverse effects (RR=
      2.20, 95% CI= 1.53~ 3.18, based on the 1296 samples from the 23 studies).
      CONCLUSIONS: The use of the antipsychotic treatment incorporated with rTMS
      treatment can slightly improve the negative symptoms of patients with
      schizophrenia and has better acceptability and fewer adverse effects.
      Nevertheless, there is publication bias in this study and the heterogeneity of
      the study is relatively high. Therefore, we need to be cautious when interpreting
      the results.

PMID- 28765679
TI  - Placement Instability Among Young People Removed from Their Original Family and
      the Likely Mental Health Implications.
AB  - BACKGROUND: Young people in out-of-home care are more likely to experience poorer
      mental and physical health outcomes related to their peers. Stable care
      environments are essential for ameliorating impacts of disruptive early childhood
      experiences, including exposure to psychological trauma, abuse and neglect. At
      present there are very few high quality data regarding the placement stability
      history of young people in out-of-home care in Australia or other countries.
      OBJECTIVES: To undertake the first systematic census of background, care type and
      placement stability characteristics of young people living in the out-of-home
      care sector in Australia. METHODS: Data was collected from four non-government
      child and adolescent community service organisations located across metropolitan
      Melbourne in 2014. The sample comprised 322 young people (females 52.8%), aged
      between 12 - 17 years (mean age=14.86 [SD=1.63] years). RESULTS: Most young
      people (64.3%) were in home-based care settings (i.e., foster care, therapeutic
      foster care, adolescent care program, kinship care, and lead tenant care),
      relative to residential care (35.7%). However, the proportion in residential care
      is very high in this age group when compared with all children in out-of-home
      care (5%). Mean age of first removal was 9 years (SD=4.54). No gender differences
      were observed for care type characteristics. Three quarters of the sample (76.9%)
      had a lifetime history of more than one placement in the out-of-home care system,
      with more than a third (36.5%) having experienced >=5 lifetime placements.
      Relative to home-based care, young people in residential care experienced
      significantly greater placement instability (chi2=63.018, p<0.001). CONCLUSIONS:
      Placement instability is common in the out-of-home care sector. Given stable care
      environments are required to ameliorate psychological trauma and health impacts
      associated with childhood maltreatment, well-designed intervention-based research
      is required to enable greater placement stability, including strengthening the
      therapeutic capacities of out-of-home carers of young people.

PMID- 28765680
TI  - A Study of the Characteristics of Alexithymia and Emotion Regulation in Patients
      with Depression.
AB  - BACKGROUND: Even though patients with depression often show significant
      alexithymia, the underlying mechanism of their alexithymia remains unclear.
      Furthermore, few experimental studies have explored their ability to regulate
      emotions. OBJECTIVE: To explore the characteristics of alexithymia in patients
      with depression, and the relationship of depressive symptoms, alexithymia and
      emotion regulation. METHODS: A total of 36 patients with depression and 31
      healthy controls were enrolled. HAMD-24 and HAMA were used to evaluate depressive
      and anxious symptoms. Toronto Alexithymia Scale (TAS) was employed to assess
      alexithymia. A computer experiment was used to evaluate emotion regulation.
      RESULTS: 66.67% of the patients with depression were considered as having
      alexithymia, but the rate in the control group was only 3.23%. The rates showed a
      significant difference (chi2=28.661, p<0.001). The score of TAS was higher in
      patients with depression than healthy controls (t=7.378, p<0.001). In a
      computerized emotional regulation experiment, under watch-neutral conditions, the
      emotion experience ratings of patients with depression were higher than those of
      controls (t=2.080, p=0.043); while under watch-negative, negative-reappraisal and
      negative-suppression conditions, the ratings of patients with depression showed
      no difference from those of the controls. The scores of TAS were correlated with
      the HAMD-24 scores and the HAMA scores significantly in patients with depression.
      However, the ratings on the emotional regulation experiment had no correlation
      with the HAMD-24 scores, the HAMA scores or the TAS scores. CONCLUSION: The
      incidence of alexithymia is higher in patients with depression than the general
      population. The depressive symptoms may have interplay with alexithymia in
      patients with depression. Emotion regulation ability may be an independent trait
      and have nothing to do with the depressive state.

PMID- 28765681
TI  - Efficacy and Metabolic Influence on Blood-Glucose and Serum Lipid of Ziprasidone
      in the Treatment of Elderly Patients with First-Episode Schizophrenia.
AB  - BACKGROUND: As the age of the population in China rises, the occurrence of first
      episode of schizophrenia in elderly persons is also gradually increasing.
      However, studies examining selection of therapeutic drugs for this population are
      relatively few. OBJECTIVE: To examine the therapeutic efficacy and metabolic
      influence on blood-glucose and serum lipid of ziprasidone in the treatment of
      elderly patients with first-episode schizophrenia. METHODS: Using randomized
      grouping, 38 elderly patients with first-episode schizophrenia were randomly
      divided into the ziprasidone treatment group (i.e. the study group) and the
      olanzapine treatment group (i.e. the control group), with 19 cases in either
      group respectively. The positive and negative symptoms scale (PANSS) was used to
      evaluate the efficacy, and adverse drug reaction scale (TESS) was used to
      evaluate adverse drug reactions, at the points prior to the treatment, at the end
      of 4th, 8th, and 12th weeks of treatment, respectively. Fasting blood glucose
      (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein
      (LDL-c) were also measured. RESULTS: There was no significant difference between
      the two groups in PANSS score at the end of week 4, week 8 and week 12. The
      curative effect on the two groups was similar. The results of repeated measure
      ANOVA showed that there were significant differences in FBG (Ftime*group=7.539,
      p=0.001), TC(Ftime*group=32.194, p<0.001), TG(Ftime*group=488.312, p<0.001), and
      LDL-c (Ftime*group=9.380, p<0.001)between the study group and the control group
      across the different time points. CONCLUSION: Ziprasidone in the treatment of
      first episode schizophrenia in elderly patients has efficacy and less effect on
      blood-glucose and serum lipid metabolism.

PMID- 28765682
TI  - Objectives of China and the Global Mental Health Work Plan.

PMID- 28765683
TI  - The Current Situations and Needs of Mental Health in China.

PMID- 28765684
TI  - Strategic Mental Health Planning and its Practice in China: Retrospect and
      Prospect.

PMID- 28765685
TI  - Factitious Disorder - A Rare Cause for Unexplained Epistaxis.
AB  - Epistaxis or nasal bleeding is a common condition which may be severe enough to
      warrant an urgent medical or surgical treatment. Factitious epistaxis is a rare
      entity. Due to a lack of exposure in complex behavioral issues during
      undergraduate training, it is quite natural on the part of a surgeon to miss the
      underlying emotional phenomena. Here, we present a case of factitious disorder
      which presented to the surgical causality with nasal bleeding. After proper
      evaluation and liaison with the department of otorhinolaryngology, we were able
      to manage the patient with antidepressants and cognitive behavioral therapy.

PMID- 28765686
TI  - Inconsistency Between Univariate and Multiple Logistic Regressions.
AB  - Logistic regression is a popular statistical method in studying the effects of
      covariates on binary outcomes. It has been widely used in both clinical trials
      and observational studies. However, the results from the univariate regression
      and from the multiple logistic regression tend to be conflicting. A covariate may
      show very strong effect on the outcome in the multiple regression but not in the
      univariate regression, and vice versa. These facts have not been well appreciated
      in biomedical research. Misuse of logistic regression is very prevalent in
      medical publications. In this paper, we study the inconsistency between the
      univariate and multiple logistic regressions and give advice in the model section
      in multiple logistic regression analysis.

PMID- 28765687
TI  - Can a fibrotic liver afford epithelial-mesenchymal transition?
AB  - The question whether epithelial-mesenchymal transition (EMT) occurs during liver
      fibrogenesis is a controversial issue. In vitro studies confirm that hepatocytes
      or cholangiocytes undergo EMT upon transforming growth factor beta (TGF-beta)
      stimulation, whereas in vivo experiments based on genetic fate mapping of
      specific cell populations suggest that EMT does not occur in fibrotic animal
      models. In this review we present current data supporting or opposing EMT in
      chronic liver disease and discuss conditions for the occurrence of EMT in
      patients. Based on the available data and our clinical observations we
      hypothesize that EMT-like alterations in liver cirrhosis are a side effect of
      high levels of TGF-beta and other pro-fibrotic mediators rather than a biological
      process converting functional parenchyma, i.e., hepatocytes, into myofibroblasts
      at a time when essential liver functions are deteriorating.

PMID- 28765688
TI  - Impact of hepatitis C oral therapy in portal hypertension.
AB  - Chronic hepatitis C is a leading cause of morbidity and mortality, mainly related
      to fibrosis/cirrhosis and portal hypertension. Direct antiviral agents are highly
      effective and safe and can now cure > 90% of the patients. Sustained viral
      response (SVR) after interferon-based regimens has been associated with
      improvement in liver function, fibrosis and portal hypertension in a significant
      proportion of patients, although a point of no return seems to exist from which
      viral elimination is no longer capable of preventing portal hypertension
      progression and liver decompensation. Indeed, although SVR is associated with
      improvement of hepatic venous pressure gradients and therefore a decreased risk
      of de novo esophageal varices, several studies show that viral clearance does not
      eliminate the risk of variceal progression, liver decompensation and death in
      patients with pre-established portal hypertension. Although evidence about the
      effects of direct antiviral agents (DAAs) on clinically significant outcomes is
      still scarce and with short follow-up, DAAs can decrease the burden of the
      disease if patients are timely treated before significant fibrosis and portal
      hypertension develops. Studies with longer follow-up are waited to establish the
      real magnitude of hepatitis C treatment on portal hypertension. Future studies
      should also focus on predictors of portal hypertension resolution since it can
      influence management and avoid unnecessary monitoring.

PMID- 28765689
TI  - Present and future of metastatic colorectal cancer treatment: A review of new
      candidate targets.
AB  - In the last two decades, great efforts have been made in the treatment of
      metastatic colorectal cancer (mCRC) due to the approval of new target agents for
      cytotoxic drugs. Unfortunately, a large percentage of patients present with
      metastasis at the time of diagnosis or relapse after a few months. The complex
      molecular heterogeneity of this disease is not completely understood; to date,
      there is a lack of predictive biomarkers that can be used to select subsets of
      patients who may respond to target drugs. Only the RAS-mutation status is used to
      predict resistance to anti-epidermal growth factor receptor agents in patients
      with mCRC. In this review, we describe approved targeted therapies for the
      management of metastatic mCRC and discuss new candidate targets on the horizon.

PMID- 28765691
TI  - Fibrinogen deficiency suppresses the development of early and delayed radiation
      enteropathy.
AB  - AIM: To determine the mechanistic role of fibrinogen, a key regulator of
      inflammation and fibrosis, in early and delayed radiation enteropathy. METHODS:
      Fibrinogen wild-type (Fib+/+), fibrinogen heterozygous (Fib+/-), and fibrinogen
      knockout (Fib-/-) mice were exposed to localized intestinal irradiation and
      assessed for early and delayed structural changes in the intestinal tissue. A 5
      cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x
      irradiation. Intestinal tissue injury was assessed by quantitative histology,
      morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma
      fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTS:
      There was no difference between sham-irradiated Fib+/+ and Fib+/- mice in terms
      of fibrinogen concentration in plasma and intestinal tissue, intestinal
      histology, morphometry, intestinal smooth muscle cell proliferation, and
      neutrophil infiltration. Therefore, Fib+/- mice were used as littermate controls.
      Unlike sham-irradiated Fib+/+ and Fib+/- mice, no fibrinogen was detected in the
      plasma and intestinal tissue of sham-irradiated Fib-/- mice. Moreover, fibrinogen
      level was not elevated after irradiation in the intestinal tissue of Fib-/- mice,
      while significant increase in intestinal fibrinogen level was noticed in
      irradiated Fib+/+ and Fib+/- mice. Importantly, irradiated Fib-/- mice exhibited
      substantially less overall intestinal structural injury (RIS, P = 0.000002),
      intestinal wall thickness (P = 0.003), intestinal serosal thickness (P = 0.009),
      collagen deposition (P = 0.01), TGF-beta immunoreactivity (P = 0.03), intestinal
      smooth muscle proliferation (P = 0.046), neutrophil infiltration (P = 0.01), and
      intestinal mucosal injury (P = 0.0003), compared to irradiated Fib+/+ and Fib+/-
      mice at both 2 wk and 26 wk. CONCLUSION: These data demonstrate that fibrinogen
      deficiency directly attenuates development of early and delayed radiation
      enteropathy. Fibrinogen could be a novel target in treating intestinal damage.

PMID- 28765692
TI  - Helicobacter pylori vacA genotype is a predominant determinant of immune response
      to Helicobacter pylori CagA.
AB  - AIM: To evaluate the frequency of Helicobacter pylori (H. pylori) CagA antibodies
      in H. pylori infected subjects and to identify potential histopathological and
      bacterial factors related to H. pylori CagA-immune response. METHODS: Systematic
      data to H. pylori isolates, blood samples, gastric biopsies for histological and
      molecular analyses were available from 99 prospectively recruited subjects.
      Serological profile (anti-H. pylori, anti-CagA) was correlated with H. pylori
      isolates (cagA, EPIYA, vacA s/m genotype), histology (Sydney classification) and
      mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected H. pylori
      strains were assessed for H. pylori CagA protein expression and IL-8 induction in
      co-cultivation model with AGS cells. RESULTS: Thirty point three percent of
      microbiologically confirmed H. pylori infected patients were seropositive for
      CagA. Majority of H. pylori isolates were cagA gene positive (93.9%) with
      following vacA polymorphisms: 42.4% vacA s1m1, 23.2% s1m2 and 34.3% s2m2. Anti
      CagA-IgG seropositivity was strongly associated with atrophic gastritis,
      increased mucosal inflammation according to the Sydney score, IL-8 and cagA mRNA
      expression. VacA s and m polymorphisms were the major determinants for positive
      (vacA s1m1) or negative (vacA s2m2) anti-CagA serological immune response, which
      also correlated with the in vitro inflammatory potential in AGS cells. In vitro
      co-cultivation of representative H. pylori strains with AGS cells confirmed
      functional CagA translocation, which showed only partial correlation with CagA
      seropositivity in patients, supporting vacA as major co-determinant of the immune
      response. CONCLUSION: Serological immune response to H. pylori cagA+ strain in H.
      pylori infected patients is strongly associated with vacA polymorphism,
      suggesting the crucial role of bacterial factors in immune and clinical phenotype
      of the infection.

PMID- 28765693
TI  - Jianpi Qingchang decoction regulates intestinal motility of dextran sulfate
      sodium-induced colitis through reducing autophagy of interstitial cells of Cajal.
AB  - AIM: To investigate the underlying effect of Jianpi Qingchang decoction (JQD)
      regulating intestinal motility of dextran sulfate sodium (DSS)-induced colitis in
      mice. METHODS: C57BL/6 mice were randomly divided into four groups: the control
      group, the DSS group, the JQD group, and the 5-aminosalicylic acid group. Except
      for the control group, colitis was induced in other groups by giving distilled
      water containing 5% DSS. Seven days after modeling, the mice were administered
      corresponding drugs intragastrically. The mice were sacrificed on the 15th day.
      The disease activity index, macroscopic and histopathologic lesions, and
      ultrastructure of colon interstitial cells of Cajal (ICC) were observed. The
      levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10
      and interferon gamma (IFN-gamma), the expression of nuclear factor-kappa B (NF
      kappaB) p65, c-kit, microtubule-associated protein 1 light chain 3 (LC3-II) and
      Beclin-l mRNA, and the colonic smooth muscle tension were assessed. RESULTS:
      Acute inflammation occurred in the mice administered DSS. Compared with the
      control group, the levels of IL-1beta, TNF-alpha, IL-10 and IFN-gamma, the
      expression of LC3-II, Beclin-1 and NF-kappaB p65 mRNA, and the contractile
      frequency increased (P < 0.05), the expression of c-kit mRNA and the colonic
      smooth muscle contractile amplitude decreased in the DSS group (P < 0.05).
      Compared with the DSS group, the levels of IL-10 and IFN-gamma, the expression of
      c-kit mRNA, and the colonic smooth muscle contractile amplitude increased (P <
      0.05), the levels of TNF-alpha and IL-1beta, the expression of LC3-II, Beclin-1
      and NF-kappaB p65 mRNA, and the contractile frequency decreased in the JQD group
      (P < 0.05). CONCLUSION: JQD can regulate the intestinal motility of DSS-induced
      colitis in mice through suppressing intestinal inflammatory cascade reaction,
      reducing autophagy of ICC, and regulating the network path of ICC/smooth muscle
      cells.

PMID- 28765690
TI  - Diarrhea after bariatric procedures: Diagnosis and therapy.
AB  - Diarrhea after bariatric procedures, mainly those with malabsorptive elements
      including Roux-Y Gastric Bypass and Biliopancreatic Diversion, is common and an
      essential determinant of quality of life and micro- and macronutrient
      deficiencies. Bariatric surgery is the only sustainably successful method to
      address morbid obesity and its comorbidities, particularly gaining more and more
      importance in the specific treatment of diabetic patients. Approximately half a
      million procedures are annually performed around the world, with numbers expected
      to rise drastically in the near future. A multitude of factors exert their
      influence on bowel habits; preoperative comorbidities and procedure-related
      aspects are intertwined with postoperative nutritional habits. Diagnosis may be
      challenging owing to the characteristics of post-bariatric surgery anatomy with
      hindered accessibility of excluded segments of the small bowel and restriction at
      the gastric level. Conventional testing measures, if available, generally yield
      low accuracy and are usually not validated in this specific population. Limited
      trials of empiric treatment are a practical alternative and oftentimes an
      indispensable part of the diagnostic process. This review provides an overview of
      causes for chronic post-bariatric surgery diarrhea and details the
      particularities of its diagnosis and treatment in this specific patient
      population. Topics of current interest such as the impact of gut microbiota and
      the influence of bile acids on morbid obesity and especially their role in
      diarrhea are highlighted in order to provide a better understanding of the
      specific problems and chances of future treatment in post-bariatric surgery
      patients.

PMID- 28765694
TI  - Lactobacillus acidophilus alleviates pouchitis after ileal pouch-anal anastomosis
      in rats.
AB  - AIM: To assess the therapeutic potential of Lactobacillus acidophilus (LA) for
      the treatment of pouchitis in a rat model. METHODS: Sprague Dawley rats underwent
      proctocolectomy and ileal pouch-anal anastomosis followed by administration of
      dextran sulfate sodium (DSS) to induce pouchitis. Rats with pouchitis were
      randomly divided into three groups: no intervention (NI), normal saline (NS, 3
      mL/d normal saline for 7 d), and LA (3 mL/d LA at 1* 1010 colony-forming units
      for 7 d). General body condition was recorded and pouch specimens were obtained
      for histological examination. mRNA expression levels of interleukin (IL)-1beta,
      IL-6, IL-10, and tumor necrosis factor-alpha were determined by RT-PCR. Zonula
      occludens protein 1 (ZO-1) levels were measured by immunohistochemistry. RESULTS:
      LA reduced weight loss associated with pouchitis (P < 0.05) and improved the
      symptoms of pouchitis in rats. Compared with the NI and NS groups, rats in the LA
      group showed earlier disappearance of hematochezia (6.17 +/- 0.75, 6.50 +/- 0.55,
      3.17 +/- 0.75, P < 0.05) and higher fecal scores (2.67 +/- 0.48, 2.50 +/- 0.51,
      4.42 +/- 0.50, respectively, P < 0.05). Histological scores were also lower in
      the LA group compared with the other two groups (7.17 +/- 0.98, 8.00 +/- 0.89,
      4.00 +/- 0.89, respectively, P < 0.05). mRNA expression levels of IL-1beta, IL-6,
      and tumor necrosis factor-alpha were significantly reduced, while IL-10 mRNA
      levels were significantly increased in the LA group (P < 0.05, respectively). ZO
      1 protein levels were also significantly increased after administration of LA (P
      < 0.05). CONCLUSION: LA alleviates pouchitis induced by DSS after ileal pouch
      anal anastomosis by decreasing pro-inflammatory factors and increasing anti
      inflammatory factors, and restoring ZO-1 expression in the mucosa.

PMID- 28765695
TI  - Effect of EPEC endotoxin and bifidobacteria on intestinal barrier function
      through modulation of toll-like receptor 2 and toll-like receptor 4 expression in
      intestinal epithelial cell-18.
AB  - AIM: To investigate toll-like receptor 2 (TLR2) and TLR4 expression, following
      bifidobacteria and low-dose EPEC endotoxin treatment, and intestinal barrier
      function in rat intestinal epithelial cell18 (IEC18). METHODS: Six experimental
      groups were established - normal control, EPEC, Bifidobacteria infantis (B.
      infantis), B. longum, B. bifidum, and B. youth groups. Optimal EPEC endotoxin
      concentration, bifidobacteria fold dilution, and treatment duration were
      determined. Quantitative real-time polymerase chain reaction and western blot,
      respectively, were conducted to detect TLR2 and TLR4 mRNA and protein expression
      in IEC-18 cells. Transepithelial electrical resistance (TEER) was measured by the
      EVOM chopstick voltohmmeter in each group. All experiments were conducted in
      triplicate and data were analyzed on SPSS 16. RESULTS: TLR2 and TLR4 mRNA and
      protein expression in the EPEC group were significantly higher than in the
      control group (P < 0.05). TLR2 mRNA and protein expression in the B. infantis, B.
      longum and B. youth groups were significantly lower than in the normal control
      group (P < 0.05). TLR4 mRNA and protein expression in the B. bifidum and B. youth
      groups were significantly lower than in normal controls (P < 0.05). In addition,
      the TEER in B. infantis, B. longum, B. bifidum, and B. youth groups were
      decreased by 19%, 18%, 23% and 23%, respectively, after 120 min of intervention,
      as compared to the control group. However, the TEER in the EPEC group was
      significantly decreased by 67% in comparison to the normal control group (P <
      0.05). CONCLUSION: Bifidobacteria protect IEC-18 cells against injury by down
      regulating TLR2 and TLR4 expression and enhance intestinal barrier function to
      protect the intestinal epithelial cells from pathogenic invasion.

PMID- 28765696
TI  - Hospital costs, length of stay and prevalence of hip and knee arthroplasty in
      patients with inflammatory bowel disease.
AB  - AIM: To examined the prevalence of hip and knee arthroplasty in patients with
      inflammatory bowel disease (IBD) by comparing the diagnostic codes for these
      procedures in patients with IBD and a control group of patients. METHODS: The
      National Inpatient Sample database (NIS) is part of the Healthcare Cost and
      Utilization Project (HCUP), the largest publicly available inpatient healthcare
      database in the United States. The NIS samples about 20% of discharges from all
      community hospitals participating in HCUP, representative of more than 95% of the
      United States population, with approximately 7000000 hospitalizations reported
      annually. NIS contains data on diagnoses, procedures, demographics, length of
      stay (LOS), co-morbidities and outcomes. ICD-9-CM diagnostic codes for primary
      hospitalizations for arthroplasty of the hip or knee with a co-diagnosis of IBD
      [combining both Crohn's disease (CD) and ulcerative colitis (UC)] were used to
      identify study subjects for cost and LOS analysis for NIS from 1999-2012.
      Statistical analysis: 1: 2 propensity score matching between IBD vs a control
      group based on following factors: Patient age, gender, race, total co
      morbidities, # of procedures, admission type, insurance, income quartiles, and
      hospital bed size, location and hospital teaching status. Categorical variables
      were reported as frequency and compared by chi2 tests or Fisher's exact tests.
      Individual 1:3 matching was also performed for patients carrying diagnostic codes
      for CD and for patients with the diagnostic code for UC. After matching,
      continuous variables were rcompared with Wilcoxon signed rank or Paired T-tests.
      Binary outcomes were compared with the McNemar's test. This process was performed
      for the diagnosis of hip or knee arthroplasty and IBD (CD and UC combined).
      Prevalence of the primary or secondary diagnostic codes for these procedures in
      patients with IBD was determined from NIS 2007. RESULTS: Costs and mortality were
      similar for patients with IBD and controls, but LOS was significantly longer for
      hip arthroplasties patients with IBD, (3.85 +/-2.59 d vs 3.68 +/-2.54 d,
      respectively, P = 0.009). Costs, LOS and survival from the procedures was similar
      in patients with CD and UC compared to matched controls. These results are shown
      in Tables 1-10. The prevalence of hip arthroplasty in patients with IBD was 0.5%
      in 2007, (170/33783 total patients with diagnostic codes for IBD) and was 0.66%
      in matched controls (P = 0.0012). The prevalence of knee arthroplasty in patients
      with IBD was 1.36, (292/21202 IBD patients) and was 2.22% in matched controls (P
      < 0.0001). CONCLUSION: Costs and mortality rates for hip and knee arthroplasties
      are the same in patients with IBD and the general population, while a statistical
      but non-relevant increase in LOS is seen for hip arthroplasties in patients with
      IBD. Compared to the general population, arthroplasties of the hip and knee are
      less prevalent in hospitalized patients with IBD.

PMID- 28765697
TI  - Eight-week ledipasvir/sofosbuvir in non-cirrhotic, treatment-naive hepatitis C
      genotype-1 patients with hepatitis C virus-RNA < 6 million: Single center, real
      world effectiveness and safety.
AB  - AIM: To evaluate sustained viral response (SVR) of 8-wk ledipasvir/sofosbuvir
      therapy among non-cirrhotic, genotype-1 hepatitis C virus (HCV) patients with RNA
      < 6 million IU/mL. METHODS: We performed a retrospective cohort study to examine
      SVR rates, predictors of treatment failure and safety analysis of 8-wk
      ledipasvir/sofosbuvir (LDV/SOF) therapy among non-cirrhotic, genotype 1 HCV
      patients with viral load < 6 million IU/mL. Primary outcome was an achievement of
      SVR at 12 wk after treatment. Secondary outcomes were identifying predictors of
      treatment failure and adverse events during treatment. RESULTS: Total 736
      patients: 55% males, 51% Caucasians and 65% were genotype 1a. Non-cirrhotic state
      of 53% was determined by clinical judgment (imaging, AST, platelet count) and 47%
      had documented liver fibrosis testing (biopsy, vibration-controlled transient
      elastography, serum biomarkers). Overall SVR12 was 96%. No difference in SVR12
      was seen between patients whose non-cirrhotic state was determined by clinical
      judgment and patients who had fibrosis testing. Age groups, gender, ethnicity and
      genotype 1 subtype did not predict SVR. Non-cirrhotic state determined by
      clinical judgment based on simple, non-invasive tests were not associated with
      lower SVR [OR = 1.02, 95%CI: 0.48-2.17, P = 0.962]. The AUROC for hepatitis C RNA
      viral load was 0.734 (P < 0.001, 95%CI: 0.66-0.82). HCV RNA 2.2 million IU/mL was
      identified as the cutoff value with sensitivity 73% and specificity 64%. HCV RNA
      < 2.2 million IU/mL was associated with significantly higher SVR 98% with OR =
      0.22 (95%CI: 0.1-0.49, P < 0.001) compared to SVR 92% in HCV RNA >= 2.2 million
      IU/mL. No death or morbidities were reported. CONCLUSION: Our outcomes validate
      safety and effectiveness of 8-wk LDV/SOF therapy in non-cirrhotic, untreated HCV
      genotype 1 patients with HCV RNA < 6 million IU/mL.

PMID- 28765698
TI  - Early radiological assessment of locally advanced pancreatic cancer treated with
      electrochemotherapy.
AB  - AIM: To report early imaging assessment of ablated area post electrochemotherapy
      (ECT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: ECT
      was performed in 19 LAPC patients enrolled in an approved ongoing clinical phase
      I/II study. Before and after ECT, 18 patients underwent computed tomography (CT)
      scan, 11 patients underwent morphological and functional magnetic resonance (MR)
      scan (dynamic contrast enhanced-MRI) calculating wash-in slope (WIS) and wash-out
      slope (WOS); diffusion weighted imaging calculating pseudo-diffusivity (Dp),
      perfusion fraction (fp) and tissue diffusivity (Dt); 10 patients underwent
      positron emission tomography (PET). Response evaluation criteria in solid tumour
      (RECIST) on MR and CT were used to assess tumour therapy response. Choi on CT,
      PET response criteria in solid tumors (PERCIST) on PET and functional parameters
      on MR were used to evaluate treatment response. RESULTS: For each patient no
      significant reduction was measurable by CT and MR using RECIST. According Choi
      criteria a partial response was obtained in 18/18 (100.0%) patients. According
      PERCIST criteria 6/10 (60.0%) patients showed a partial response, 3/10 (30.0%)
      stable disease and 1/10 (10.0%) progression disease. Moreover, using functional
      MR parameters, a significant reduction of viable tumour after ECT can be
      observed. According DeltaWIS and DeltaWOS 9/11 (81.8%) patients exhibited a
      partial response and 2/11 (18.2%) stable disease; 8/11 (72.7%) patients were
      considered in partial response by DeltaDp evaluation and 3/11 (27.3%) in stable
      disease; according DeltaDt 7/11 (63.6%) patients showed a partial response, 1/11
      (9.1%) showed progression of disease and 3/11 (27.3%) were stable. Perfusion
      fraction fp showed a significant reduction after ECT only in four patients. No
      significant difference was observed after ECT in signal intensity of T1-weighted
      images and T2-weighted images, and in equilibrium-phase of contrast study,
      according to chi2 test was observed. A good correlation was reported between
      DeltaHounsfield unit and Deltamaximum standardized uptake value and between
      Deltafp and DeltaWOS, with a significant statistically difference (P < 0.05)
      using Spearman correlation coefficient. CONCLUSION: Perfusion and diffusion MR
      derived parameters, Choi, PERCIST criteria are more performant than morphological
      MR and CT criteria to assess ECT treatment response.

PMID- 28765699
TI  - Effect of initial stent position on patency of transjugular intrahepatic
      portosystemic shunt.
AB  - AIM: To evaluate the effect of initial stent position on transjugular
      intrahepatic portosystemic shunt (TIPS). METHODS: We studied 425 patients from
      January 2004 to January 2015 with refractory ascites or variceal bleeding who
      required TIPS placement. Patients were randomly divided into group A (stent in
      hepatic vein, n = 57), group B (stent extended to junction of hepatic vein and
      inferior vena cava, n = 136), group C (stent in left branch of portal vein, n =
      83) and group D (stent in main portal vein, n = 149). Primary unassisted patency
      was compared using Kaplan-Meier analysis, and incidence of recurrence of
      bleeding, ascites and hepatic encephalopathy (HE) were analyzed. RESULTS: The
      mean primary unassisted patency rate in group B tended to be higher than in group
      A at 3, 6 and 12 mo (P = 0.001, 0.000 and 0.005), and in group D it tended to be
      lower than in group C at 3, 6 and 12 mo (P = 0.012, 0.000 and 0.028). The median
      shunt primary patency time for group A was shorter than for group B (5.2 mo vs
      9.1 mo, 95%CI: 4.3-5.6, P = 0.013, log-rank test), while for group C it was
      longer than for group D (8.3 mo vs 6.9 mo, 95%CI: 6.3-7.6, P = 0.025, log-rank
      test). Recurrence of bleeding and ascites in group A was higher than in group B
      at 3 mo (P = 0.014 and 0.020), 6 mo (P = 0.014 and 0.019) and 12 mo (P = 0.024
      and 0.034. Recurrence in group D was higher than in group C at 3 mo (P = 0.035
      and 0.035), 6 mo (P = 0.038 and 0.022) and 12 mo (P = 0.017 and 0.009). The
      incidence of HE was not significantly different among any of the groups (P =
      0.965). CONCLUSION: The initial stent position can markedly affect stent patency,
      which potentially influences the risk of recurrent symptoms associated with shunt
      stenosis or occlusion.

PMID- 28765700
TI  - Endoscopy is of low yield in the identification of gastrointestinal neoplasia in
      patients with dermatomyositis: A cross-sectional study.
AB  - AIM: To determine the prevalence of gastrointestinal neoplasia among
      dermatomyositis patients who underwent an esophagogastroduodenoscopy and/or
      colonoscopy. METHODS: A cross-sectional study examining the results of upper
      endoscopy and colonoscopy in adults with dermatomyositis at an urban, university
      hospital over a ten year period was performed. Chart review was performed to
      confirm the diagnosis of dermatomyositis. Findings on endoscopy were collected
      and statistical analyses stratified by age and presence of symptoms were
      performed. RESULTS: Among 373 adult patients identified through a code based
      search strategy, only 163 patients had dermatomyositis confirmed by chart review.
      Of the 47 patients who underwent upper endoscopy, two cases of Barrett's
      esophagus without dysplasia were identified and there were no cases of
      malignancy. Of the 67 patients who underwent colonoscopy, no cases of malignancy
      were identified and an adenoma was identified in 15% of cases. No significant
      differences were identified in the yield of endoscopy when stratified by age or
      presence of symptoms. CONCLUSION: The yield of endoscopy is low in patients with
      dermatomyositis and is likely similar to the general population; we identified no
      cases of malignancy. A code based search strategy is inaccurate for the diagnosis
      of dermatomyositis, calling into question the results of prior population-based
      studies. Larger studies with rigorously validated search strategies are necessary
      to understand the risk of gastrointestinal malignancy in patients with
      dermatomyositis.

PMID- 28765701
TI  - Levels and activities of von Willebrand factor and metalloproteinase with
      thrombospondin type-1 motif, number 13 in inflammatory bowel diseases.
AB  - AIM: To evaluate the levels of von Willebrand factor (VWF) and metalloproteinase
      with thrombospondin type-1 motif, number 13 (ADAMTS13) in inflammatory bowel
      disease (IBD) and correlate them with the disease activity. METHODS: Consecutive
      patients with IBD aged 18 years or older were enrolled in the study. Forty-seven
      patients with ulcerative colitis (UC), 38 with Crohn's disease (CD), and 50
      healthy controls were included. The white blood cell count, haematocrit, platelet
      count, fibrinogen, partial activated thromboplastin time, C-reactive protein,
      albumin, VWF antigen level (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo),
      VWF collagen-binding activity (VWF:CB), and ADAMTS13 antigen level (ADAMTS13:Ag)
      and activity (ADAMTS13act) were measured. The following ratios were assessed:
      VWF:RCo/VWF:Ag, VWF:CB/VWF:Ag, VWF:Ag/ADAMTS13act, and ADAMTS13act/ADAMTS13:Ag.
      RESULTS: Compared to controls, the odds ratio (OR) of an elevated VWF: Ag > 150%
      was 8.7 (95%CI: 2.7-28.1) in the UC group and 16.2 (95%CI: 4.8-54.0) in the CD
      group. VWF:CB was lower in UC patients, and active CD was associated with a
      higher VWF: RCo (+38%). The ORs of VWF:CB/VWF:Ag < 0.7 (a marker of acquired von
      Willebrand syndrome) in the UC and CD groups were 11.9 (95%CI: 4.4-32.4) and 13.3
      (95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag
      (-23%) and ADAMTS13act (-20%) compared to UC in remission. Patients with active
      CD had a 15% lower ADAMTS13act than controls. The activity of UC, but not that of
      CD, was inversely correlated with ADAMTS13:Ag (r = -0.76) and ADAMTS13act (r = 
      0.81). CONCLUSION: Complex VWF-ADAMTS13-mediated mechanisms disturb haemostasis
      in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13
      level combined with an elevated VWF:Ag could predispose one to thrombosis.

PMID- 28765702
TI  - Predictors of esophageal varices and first variceal bleeding in liver cirrhosis
      patients.
AB  - AIM: To assess "predictors" of esophageal varices (EV) and variceal bleeding
      using non-invasive markers in Albanian patients diagnosed with liver cirrhosis.
      METHODS: One hundred thirty-nine newly diagnosed cirrhotic patients without
      variceal bleeding were included in this analysis. Model for end-stage liver
      disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase
      (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), platelet count to
      spleen diameter (PC/SD), fibrosis-4-index (FIB-4), fibrosis index (FI) and King's
      Score were measured for all participants. All patients underwent endoscopic
      assessment within two days of hospitalization. The major end point was the first
      esophageal variceal bleeding (EVB) event. The diagnostic performance of
      "predictors" for the presence of EV and EVB were assessed by sensitivity and
      specificity values obtained from the receiver operating characteristics
      procedure. RESULTS: FIB-4 was the only strong and significant "predictor" of
      esophageal varices (multivariable-adjusted OR = 1.57 for one unit increment;
      95%CI: 1.15-2.14). Furthermore, a cut-off value of 3.23 for FIB-4 was a
      significant predictor of esophageal varices, with a sensitivity of 72%, a
      specificity of 58% and a proportion of area under the curve (AUC) of 66% (P =
      0.01). During the follow-up (median: 31.5 mo; interquartile range: 11-59 mo), 34
      patients (24%) experienced a first EVB. FIB-4 was a poor predictor of EVB (the
      AUC was only 51%) for a cut-off value of 5.02. Furthermore, the AUC of AST/ALT,
      APRI, PC/SD, FI, MELD and King's Score ranged from 45% to 55%. None of the non
      invasive markers turned out to be a useful predictor of EVB. CONCLUSION: Despite
      the low diagnostic accuracy, FIB-4 appears the most efficient non-invasive liver
      fibrosis marker which can be used as an initial screening tool for cirrhotic
      patients.

PMID- 28765703
TI  - Extreme liver resections with preservation of segment 4 only.
AB  - AIM: To evaluate safety and outcomes of a new technique for extreme hepatic
      resections with preservation of segment 4 only. METHODS: The new method of
      extreme liver resection consists of a two-stage hepatectomy. The first stage
      involves a right hepatectomy with middle hepatic vein preservation and induction
      of left lobe congestion; the second stage involves a left lobectomy. Thus, the
      remnant liver is represented by the segment 4 only (with or without segment 1, +/
      S1). Five patients underwent the new two-stage hepatectomy (congestion group).
      Data from volumetric assessment made before the second stage was compared with
      that of 10 matched patients (comparison group) that underwent a single-stage
      right hepatectomy with middle hepatic vein preservation. RESULTS: The two stages
      of the procedure were successfully carried out on all 5 patients. For the
      congestion group, the overall volume of the left hemiliver had increased 103%
      (mean increase from 438 mL to 890 mL) at 4 wk after the first stage of the
      procedure. Hypertrophy of the future liver remnant (i.e., segment 4 +/- S1) was
      higher than that of segments 2 and 3 (144% vs 54%, respectively, P < 0.05). The
      median remnant liver volume-to-body weight ratio was 0.3 (range, 0.28-0.40)
      before the first stage and 0.8 (range, 0.45-0.97) before the second stage. For
      the comparison group, the rate of hypertrophy of the left liver after right
      hepatectomy with middle hepatic vein preservation was 116% +/- 34%. Hypertrophy
      rates of segments 2 and 3 (123% +/- 47%) and of segment 4 (108% +/- 60%, P >
      0.05) were proportional. The mean preoperative volume of segments 2 and 3 was 256
      +/- 64 cc and increased to 572 +/- 257 cc after right hepatectomy. Mean
      preoperative volume of segment 4 increased from 211 +/- 75 cc to 439 +/- 180 cc
      after surgery. CONCLUSION: The proposed method for extreme hepatectomy with
      preservation of segment 4 only represents a technique that could allow complete
      resection of multiple bilateral liver metastases.

PMID- 28765704
TI  - Predictive factors for body weight loss and its impact on quality of life
      following gastrectomy.
AB  - AIM: To determine the predictive factors and impact of body weight loss on
      postgastrectomy quality of life (QOL). METHODS: We applied the newly developed
      integrated questionnaire postgastrectomy syndrome assessment scale-45, which
      consists of 45 items including those from the Short Form-8 and Gastrointestinal
      Symptom Rating Scale instruments, in addition to 22 newly selected items. Between
      July 2009 and December 2010, completed questionnaires were received from 2520
      patients with curative resection at 1 year or more after having undergone one of
      six types of gastrectomy for Stage I gastric cancer at one of 52 participating
      institutions. Of those, we analyzed 1777 eligible questionnaires from patients
      who underwent total gastrectomy with Roux-en-Y procedure (TGRY) or distal
      gastrectomy with Billroth-I (DGBI) or Roux-en-Y (DGRY) procedures. RESULTS: A
      total of 393, 475 and 909 patients underwent TGRY, DGRY, and DGBI, respectively.
      The mean age of patients was 62.1 +/- 9.2 years. The mean time interval between
      surgery and retrieval of the questionnaires was 37.0 +/- 26.8 mo. On multiple
      regression analysis, higher preoperative body mass index, total gastrectomy, and
      female sex, in that order, were independent predictors of greater body weight
      loss after gastrectomy. There was a significant difference in the degree of
      weight loss (P < 0.001) among groups stratified according to preoperative body
      mass index (< 18.5, 18.5-25 and > 25 kg/m2). Multiple linear regression analysis
      identified lower postoperative body mass index, rather than greater body weight
      loss postoperatively, as a certain factor for worse QOL (P < 0.0001) after
      gastrectomy, but the influence of both such factors on QOL was relatively small
      (R2, 0.028-0.080). CONCLUSION: While it is certainly important to maintain
      adequate body weight after gastrectomy, the impact of body weight loss on QOL is
      unexpectedly small.

PMID- 28765705
TI  - Divergent expression of bacterial wall sensing Toll-like receptors 2 and 4 in
      colorectal cancer.
AB  - AIM: To characterize the expression of toll-like receptors (TLR) 2 and 4 in
      colorectal cancer (CRC) and in normal colorectal mucosa. METHODS: We analysed
      tissue samples from a prospective series of 118 unselected surgically treated
      patients with CRC. Sections from formalin fixed, paraffin embedded specimens were
      analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent
      assessors evaluated separately expression at the normal mucosa, at the invasive
      front and the bulk of the carcinoma, and in the lymph node metastases when
      present. Expression levels in different locations were compared and their
      associations with clinicopathological features including TNM-stage and the grade
      of the tumour and 5-year follow-up observations were analysed. RESULTS: Normal
      colorectal epithelium showed a gradient of expression of both TLR2 and TLR4 with
      low levels in the crypt bases and high levels in the surface. In CRC, expression
      of both TLRs was present in all cases and in the major proportion of tumour
      cells. Compared to normal epithelium, TLR4 expression was significantly weaker
      but TLR2 expression stronger in carcinoma cells. Weak TLR4 expression in the
      invasive front was associated with distant metastases and worse cancer-specific
      survival at 5 years. In tumours of the proximal colon the cancer-specific
      survival at 5 years was 36.9% better with strong TLR4 expression as compared with
      those with weak expression (P = 0.044). In contrast, TLR2 expression levels were
      not associated with prognosis. Tumour cells in the lymph node metastases showed
      higher TLR4 expression and lower TLR2 expression than cells in primary tumours.
      CONCLUSION: Tumour cells in CRC show downregulation of TLR4 and upregulation of
      TLR2. Low expression of TLR4 in the invasive front predicts poor prognosis and
      metastatic disease.

PMID- 28765706
TI  - Non-invasive assessment of liver fibrosis using two-dimensional shear wave
      elastography in patients with autoimmune liver diseases.
AB  - AIM: To determine the diagnostic accuracy of two-dimensional shear wave
      elastography (2D-SWE) for the non-invasive assessment of liver fibrosis in
      patients with autoimmune liver diseases (AILD) using liver biopsy as the
      reference standard. METHODS: Patients with AILD who underwent liver biopsy and 2D
      SWE were consecutively enrolled. Receiver operating characteristic (ROC) curves
      were constructed to assess the overall accuracy and to identify optimal cut-off
      values. RESULTS: The characteristics of the diagnostic performance were
      determined for 114 patients with AILD. The areas under the ROC curves for
      significant fibrosis, severe fibrosis, and cirrhosis were 0.85, 0.85, and 0.86,
      respectively, and the optimal cut-off values associated with significant fibrosis
      (>= F2), severe fibrosis (>= F3), and cirrhosis (F4) were 9.7 kPa, 13.2 kPa and
      16.3 kPa, respectively. 2D-SWE showed sensitivity values of 81.7% for significant
      fibrosis, 83.0% for severe fibrosis, and 87.0% for cirrhosis, and the respective
      specificity values were 81.3%, 74.6%, and 80.2%. The overall concordance rate of
      the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages was
      53.5%. CONCLUSION: 2D-SWE showed promising diagnostic performance for assessing
      liver fibrosis stages and exhibited high cut-off values in patients with AILD.
      Low overall concordance rate was observed in the liver stiffness measurements
      obtained using 2D-SWE vs fibrosis stages.

PMID- 28765707
TI  - Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast
      agent based on biotin-avidin-specific binding.
AB  - Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity
      and specificity was essential to increase MRI diagnostic sensitivity and
      accuracy. In this study, the MRI contrast agent, vascular endothelial growth
      factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine
      pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was
      designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL
      DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA
      Gd using biotin-avidin reaction. In vitro cytotoxicity study results showed that
      VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental
      concentrations. In cell uptake experiments, VPDG could significantly increase the
      internalization rates (61.75%+/-5.22%) in VEGFR-positive HepG2 cells compared to
      PLL-DTPA-Gd (PDG) (25.16%+/-4.71%, P<0.05). In MRI studies in vitro,
      significantly higher T1 relaxivity (14.184 mM-1 s-1) was observed compared to
      Magnevist(r) (4.9 mM-1 s-1; P<0.01). Furthermore, in vivo MRI study results
      showed that VPDG could significantly enhance the tumor signal intensity and
      prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that
      macromolecular VPDG was a promising MRI contrast agent and held great potential
      for molecular diagnosis of tumor.

PMID- 28765709
TI  - Prevalence, symptomatic features, and factors associated with sleep
      disturbance/insomnia in Japanese patients with type-2 diabetes.
AB  - PURPOSE: To clarify the prevalence and symptomatic characteristics of sleep
      disturbance/insomnia among type-2 diabetes mellitus (DM) Japanese patients.
      METHODS: A cross-sectional survey of Japanese patients with the disorder was
      conducted. Participants consisted of 622 type-2 DM patients (mean 56.1+/-9.56
      years) and 622 sex- and age-matched controls. Participants' scores in the
      Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J), the Japanese
      version of the 12-item Center for Epidemiologic Studies Depression Scale (CES-D),
      the Medical Outcomes Study 8-item Short Form Health Survey (SF-8), and the
      glycated hemoglobin A1c (HbA1c) of type-2 DM patients were analyzed. RESULTS:
      There were 253 poor sleepers (43.9%) in the type-2 DM group as a result of
      dichotomization with the PSQI-J cutoff total score of 5.5. The type-2 DM group
      recorded a higher mean PSQI-J total score (P<0.01) and manifested poorer sleep
      maintenance. Poor sleepers in both groups had lower mental component summary from
      SF-8 (MCS), physical component summary from SF-8 (PCS), and CES-D than good
      sleepers, and good sleepers in both groups had higher MCS, PCS, and CES-D than
      poor sleepers. Higher body mass index, presence of smoking habit, and living
      alone were significantly associated with sleep disturbance/insomnia symptoms, but
      HbA1c was not associated with sleep disturbance/insomnia in the type-2 DM group.
      CONCLUSION: Individuals affected with type-2 DM are likely to experience sleep
      problems, characterized by disturbance in sleep maintenance. Sleep
      disturbance/insomnia symptoms in DM patients might considerably reduce health
      related quality of life.

PMID- 28765708
TI  - Folate-modified Annonaceous acetogenins nanosuspensions and their improved
      antitumor efficacy.
AB  - Annonaceous acetogenins (ACGs) are a large family of fatty acid derived natural
      products that are exclusively isolated from the Annonaceae species. Many members
      of this diverse family have a broad spectrum of biological activities, the most
      impressive of which is anticancer activity. However, their poor solubility and
      severe toxicity restrict their clinical application, and their complicated
      composition hinders their formulation and drug delivery. In this study, beta
      cyclodextrin was modified with folic acid (FA) and then combined with soybean
      lecithin to prepare FA-modified ACGs nanosuspensions (FA-ACGs-NSps). The obtained
      FA-ACGs-NSps had a high drug payload of 57.59% and average particle size of 199.5
      nm, and they exhibited sustained drug release within 142 hours. In comparison
      with ACGs-NSps, FA-ACGs-NSps showed significantly enhanced cytotoxicity and
      higher cell uptake toward folate receptor-positive 4T1 cell lines. An in vivo
      study demonstrated that FA-ACGs-NSps more effectively accumulated in tumors and
      enhanced the antitumor therapeutic efficacy with less toxicity in 4T1 tumor
      bearing mice. Therefore, FA-ACGs-NSps may be a promising drug delivery system for
      ACGs to improve their therapeutic window and may be suitable for clinical
      application to treat folate-positive tumors.

PMID- 28765710
TI  - Cost-utility of collaborative care for the treatment of comorbid major depressive
      disorder in outpatients with chronic physical conditions. A randomized controlled
      trial in the general hospital setting (CC-DIM).
AB  - PURPOSE: Major depressive disorder (MDD) is highly prevalent in patients with a
      chronic physical condition, and this comorbidity has a negative influence on
      quality of life, health care costs, self-care, morbidity, and mortality. Research
      has shown that collaborative care (CC) may be a cost-effective treatment.
      However, its cost-effectiveness in this patient group has not yet been
      established. Therefore, the aim of this study was to evaluate the cost-utility of
      CC for the treatment of comorbid MDD in chronically ill patients in the
      outpatient general hospital setting. The study was conducted from a health care
      and societal perspective. PATIENTS AND METHODS: In this randomized controlled
      trial, 81 patients with moderate-to-severe MDD were included; 42 were randomly
      assigned to the CC group and 39 to the care as usual (CAU) group. We applied the
      TiC-P, short-form Health-Related Quality of Life questionnaire, and EuroQol EQ-5D
      3 level version, measuring the use of health care, informal care, and household
      work, respectively, at baseline and at 3, 6, 9, and 12 months follow-up. RESULTS:
      The mean annual direct medical costs in the CC group were ?6,718 (95% confidence
      interval [CI]: 3,541 to 10,680) compared to ?4,582 (95% CI: 2,782 to 6,740) in
      the CAU group. The average quality-adjusted life years (QALYs) gained were 0.07
      higher in the CC group, indicating that CC is more costly but also more effective
      than CAU. From a societal perspective, the incremental cost-effectiveness ratio
      was ?24,690/QALY. CONCLUSION: This first cost-utility analysis in chronically ill
      patients with comorbid MDD shows that CC may be a cost-effective treatment
      depending on willingness-to-pay levels. Nevertheless, the low utility scores
      emphasize the need for further research to improve the cost-effectiveness of CC
      in this highly prevalent and costly group of patients.

PMID- 28765711
TI  - Characteristics and predictors of progression in an Egyptian multiple sclerosis
      cohort: a multicenter registry study.
AB  - BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease with a
      heterogeneous presentation and diverse disease course. Recent studies indicate a
      rising prevalence of MS in the Middle East. OBJECTIVE: To characterize the
      demographics and disease features of Egyptian patients attending four tertiary
      referral MS centers in Cairo. MATERIALS AND METHODS: This was a retrospective,
      observational study on 1,581 patients between 2001 and 2015. Medical records were
      reviewed and data were identified and extracted in a standardized electronic
      registry. RESULTS: The mean age of disease onset was 26.6+/-7.8 years, with the
      majority being female (2.11:1). Relapsing-remitting MS was the most common type
      (75.1%). The main presenting symptom was motor weakness (43.9%), which was also
      the most frequent symptom during the disease course. Family history of MS was
      found in 2.28%. Higher initial Expanded Disability Status Scale score, black
      holes, and infratentorial lesions on initial magnetic resonance imaging were
      independent factors for disease progression by univariate analysis (OR 3.87 [95%
      CI 1.84-6.51], 4.14 [95% CI 3.08-5.58], 4.07 [95% CI 3.21-4.99], respectively);
      however, in multivariate analysis, only infratentorial lesions were an
      independent risk for disease progression (OR 6, 95% CI 2.99-12.02; P=0.0005).
      CONCLUSION: The results from this registry - the largest for MS in the Arab
      region to date - are comparable to other registries with slight differences.

PMID- 28765712
TI  - Mean cost per number needed to treat with tocilizumab plus methotrexate versus
      abatacept plus methotrexate in the treatment of rheumatoid arthritis in patients
      previously treated with methotrexate.
AB  - INTRODUCTION: Biological disease-modifying antirheumatic drugs are particularly
      recommended for use in patients who are poor responders, are intolerant to
      conventional disease-modifying antirheumatic drugs (cDMARDs), or in whom
      continued treatment with cDMARDs is deemed inappropriate. We estimated the
      efficacy and treatment costs associated with the use of tocilizumab (TCZ) plus
      methotrexate (Mtx) versus abatacept (ABT) plus Mtx in the treatment of rheumatoid
      arthritis (RA) in patients previously treated with Mtx. METHODS: Clinical data
      from a Technology Appraisal Guidance published in January 2016 by the National
      Institute for Health and Care Excellence were used. Pharmacoeconomic comparison
      between biological agents was carried out to estimate the respective cost for the
      number needed to treat (NNT) compared to cDMARDs using both American College of
      Rheumatology (ACR) and European League against Rheumatism (EULAR) criteria. A 6
      month period was considered. Direct medical costs including pharmacological
      therapy, administration, and monitoring were considered. RESULTS: Using both ACR
      and EULAR criteria, TCZ subcutaneously (sc) or intravenously (iv) had a lower NNT
      (higher efficacy) compared to ABT (iv/sc). The most significant differences in
      favor of TCZ were observed using EULAR criteria. Related to the level of efficacy
      observed, TCZ (iv/sc) had a lower cost for NNT with both ACR and EULAR criteria
      compared to ABT (iv/sc). Sensitivity analysis confirmed these results.
      CONCLUSION: TCZ (iv/sc) represents a more cost-effective option than ABT (iv/sc)
      in the treatment of RA in patients previously treated with Mtx.

PMID- 28765713
TI  - Inflammatory bowel disease in Bahrain: single-center experience.
AB  - PURPOSE: The number of newly diagnosed inflammatory bowel disease (IBD) cases
      such as ulcerative colitis (UC), Crohn's disease (CD), and indeterminate colitis
      (IC) is rapidly increasing in Gulf countries and Saudi Arabia. The aim of this
      study was to investigate the incidence and prevalence of IBD in patients who have
      attended the Salmaniya Medical Complex, Bahrain, between the years 1984 and 2014.
      PATIENTS AND METHODS: All patients who had attended the Salmaniya Medical
      Complex, Bahrain, and had been diagnosed with UC, CD, or IC, between the years
      1984 and 2014, were included in the analysis. Data collected were: patient
      demographics, symptoms, clinical signs, complications, surgical interventions,
      extent of disease, endoscopic findings, histopathology, and lab measurements.
      RESULTS: A total of 187 cases were included; 61 had CD, 123 had UC, and a further
      3 cases presented with IC. A clear increase in the incidence and prevalence of
      IBD can be seen in this cohort. The prevalence of IBD was calculated to be
      26.25/105 cases. The average number of IBD cases increased from 3 cases (average
      for the years 1984-2001) to 12 cases (average for the years 2002-2014). A number
      of factors correlate positively or negatively with CD and UC. In the current
      study, a link between gastrointestinal complications in CD cases and the use of
      steroids as a treatment was noted (p-value -0.02). Age also had a significant
      influence on the need for surgery in CD cases (p-value -0.04), and a family
      history of UC was statistically linked to surgical intervention (p-value -0.05).
      CONCLUSIONS: IBD can no longer be considered a rare disease in Bahrain. The
      incidence of both UC and CD is steadily increasing. There is a need for
      increasing awareness of the Bahraini public to IBD in order for proper medical
      care to be given.

PMID- 28765714
TI  - High prevalence of subclass-specific binding and neutralizing antibodies against
      Clostridium difficile toxins in adult cystic fibrosis sera: possible mode of
      immunoprotection against symptomatic C. difficile infection.
AB  - OBJECTIVES: Despite multiple risk factors and a high rate of colonization for
      Clostridium difficile, the occurrence of C. difficile infection in patients with
      cystic fibrosis is rare. The aim of this study was to compare the prevalence of
      binding C. difficile toxin-specific immunoglobulin (Ig)A, IgG and anti-toxin
      neutralizing antibodies in the sera of adults with cystic fibrosis, symptomatic
      C. difficile infection (without cystic fibrosis) and healthy controls. METHODS:
      Subclass-specific IgA and IgG responses to highly purified whole C. difficile
      toxins A and B (toxinotype 0, strain VPI 10463, ribotype 087), toxin B from a C.
      difficile toxin-B-only expressing strain (CCUG 20309) and precursor form of B
      fragment of binary toxin, pCDTb, were determined by protein microarray.
      Neutralizing antibodies to C. difficile toxins A and B were evaluated using a
      Caco-2 cell-based neutralization assay. RESULTS: Serum IgA anti-toxin A and B
      levels and neutralizing antibodies against toxin A were significantly higher in
      adult cystic fibrosis patients (n=16) compared with healthy controls (n=17) and
      patients with symptomatic C. difficile infection (n=16); p<=0.05. The same
      pattern of response prevailed for IgG, except that there was no difference in
      anti-toxin A IgG levels between the groups. Compared with healthy controls
      (toxins A and B) and patients with C. difficile infection (toxin A), sera from
      cystic fibrosis patients exhibited significantly stronger protective anti-toxin
      neutralizing antibody responses. CONCLUSION: A superior ability to generate
      robust humoral immunity to C. difficile toxins in the cystic fibrosis population
      is likely to confer protection against symptomatic C. difficile infection. This
      protection may be lost in the post-transplantation setting, where sera monitoring
      of anti-C. difficile toxin antibody titers may be of clinical value.

PMID- 28765715
TI  - Children's International Polyposis (CHIP) study: a randomized, double-blind,
      placebo-controlled study of celecoxib in children with familial adenomatous
      polyposis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of celecoxib versus placebo in the
      prevention and treatment of colorectal polyposis in children with familial
      adenomatous polyposis (FAP). METHODS: In this Phase III, double-blind,
      randomized, placebo-controlled, multicenter trial patients aged 10-17 years with
      FAP were randomized to celecoxib (16 mg/kg/day) or placebo for up to 5 years.
      Patients underwent annual assessments, including colonoscopies, to detect the
      time from randomization to the earliest occurrence of >=20 polyps (>2 mm in size)
      or colorectal malignancy. The study was terminated early due to low rate of
      observed endpoints combined with a lower than expected enrollment rate.
      Descriptive results are provided. RESULTS: Of 106 randomized patients, 55 were
      treated with celecoxib (mean age 12.6 years; 52.7% female) and 51 were given
      placebo (mean age 12.2 years; 54.9% female). Disease progression (>=20 polyps, >2
      mm in size) was observed in seven (12.7%) and 13 (25.5%) patients, respectively.
      The median time to disease progression was 2.1 years in the celecoxib group and
      1.1 years for placebo. No patient developed colorectal cancer. The rate of
      adverse events (AEs) was similar in both groups (75.5% and 72.9%, respectively).
      Three patients in the celecoxib group (none in the placebo group) experienced
      serious AEs. CONCLUSION: In children with FAP, celecoxib was a well-tolerated
      treatment that was associated with a lower rate of colorectal polyposis and a
      longer time to disease progression compared with placebo. Due to the low rate of
      observed endpoints, the long-term impact of these results could not be
      ascertained.

PMID- 28765717
TI  - Assessing the performance and satisfaction of medical residents utilizing
      standardized patient versus mannequin-simulated training.
AB  - BACKGROUND: Conducting simulations of rapidly decompensating patients are a key
      part of internal medicine (IM) residency training. Traditionally, mannequins have
      been the simulation tool used in these scenarios. OBJECTIVE: To compare IM
      residents' performance and assess realism in specific-simulated decompensating
      patient scenarios using standardized patients (SPs) as compared to mannequin.
      METHODS: Nineteen IM residents were randomized to undergo simulations using
      either a mannequin or an SP. Each resident in the two groups underwent four
      different simulation scenarios (calcium channel blocker overdose, severe sepsis,
      severe asthma exacerbation, and acute bacterial meningitis). Residents completed
      pretest and post-test evaluations as well as a questionnaire to assess the
      reality perception (realism score). RESULTS: Nine residents completed mannequin
      based scenarios, whereas 10 completed SP-based scenarios. Improvement in the post
      test scores was seen in both groups. However, there were significantly higher
      post-test scores achieved with SP simulations in three out of the four scenarios
      (P=0.01). When compared with the mannequin group, the SP simulation group showed
      a significantly higher average realism score (P=0.002). CONCLUSIONS: Applying SP
      based specific-simulation scenarios in IM residency training may result in better
      performance and a higher sense of a realistic experience by medical residents.

PMID- 28765718
TI  - Checklist of bees (Apoidea) from a private conservation property in west-central
      Montana.
AB  - BACKGROUND: Here we present preliminary results from the first three years of a
      long-term bee survey conducted at a 3,840-ha private conservation property in the
      northern Sapphire Mountains and Bitterroot River Valley, and a pilot study at an
      associated 80-ha property in the Swan River Valley, Missoula County, Montana,
      USA. The survey includes hand-net, bowl-trap, and blue-vane trap collections. The
      resulting checklist comprises 229 bee species and morphospecies within 5
      families, 38 genera and 91 subgenera. Of the total species in the list, 34 of
      them represent first state records Montana. This survey expands the number of bee
      species recorded in Montana to 366. Included in these species is Megachile
      (Eutricharaea) apicalis Spinola, showing a range expansion for this introduced
      bee. NEW INFORMATION: We present new distributional records for 34 bee species,
      including Megachile (Eutricharaea) apicalis Spinola, an introduced bee that was
      discovered to be resident in North America in 1984 in Santa Barbara County,
      California. This species has since expanded its range in the across the west, but
      had not been previously recorded in Montana.

PMID- 28765719
TI  - Time series data of a broadleaved secondary forest in Japan as affected by deer
      and mass mortality of oak trees.
AB  - BACKGROUND: Abandonment of broadleaved secondary forests that have been used for
      various purposes may cause the loss of biodiversity. Some of these forests suffer
      from diseases such as Japanese oak wilt. An increasing number of deer also impact
      some of them. Monitoring and recording the status of such forests is important
      for their proper management. NEW INFORMATION: This data set provides a concrete
      example of temporal changes in a temperate broadleaved secondary forest. The
      forest has been damaged by mass mortality of oak trees caused by Japanese oak
      wilt disease. In addition, the forest has been under foraging pressure by sika
      deer (Cervus nippon Temminck). The data set can provide information on how such a
      forest has changed in species composition of the canopy and sub-canopy layers and
      in species occurrence in the understory layer.

PMID- 28765716
TI  - Simulation training in neurosurgery: advances in education and practice.
AB  - The current simulation technology used for neurosurgical training leaves much to
      be desired. Significant efforts are thoroughly exhausted in hopes of developing
      simulations that translate to give learners the "real-life" feel. Though a
      respectable goal, this may not be necessary as the application for simulation in
      neurosurgical training may be most useful in early learners. The ultimate
      uniformly agreeable endpoint of improved outcome and patient safety drives these
      investments. We explore the development, availability, educational taskforces,
      cost burdens and the simulation advancements in neurosurgical training. The
      technologies can be directed at achieving early resident milestones placed by the
      Accreditation Council for Graduate Medical Education. We discuss various aspects
      of neurosurgery disciplines with specific technologic advances of simulation
      software. An overview of the scholarly landscape of the recent publications in
      the realm of medical simulation and virtual reality pertaining to neurologic
      surgery is provided. We analyze concurrent concept overlap between PubMed
      headings and provide a graphical overview of the associations between these
      terms.

PMID- 28765720
TI  - A global map of saltmarshes.
AB  - BACKGROUND: Saltmarshes are extremely valuable but often overlooked ecosystems,
      contributing to livelihoods locally and globally through the associated ecosystem
      services they provide, including fish production, carbon storage and coastal
      protection. Despite their importance, knowledge of the current spatial
      distribution (occurrence and extent) of saltmarshes is incomplete. In light of
      increasing anthropogenic and environmental pressures on coastal ecosystems,
      global data on the occurrence and extent of saltmarshes are needed to draw
      attention to these critical ecosystems and to the benefits they generate for
      people. Such data can support resource management, strengthen decision-making and
      facilitate tracking of progress towards global conservation targets set by
      multilateral environmental agreements, such as the Aichi Biodiversity Targets of
      the United Nations' (UN's) Strategic Plan for Biodiversity 2011-2020, the
      Sustainable Development Goals of the UN's 2030 Agenda for Sustainable Development
      and the Ramsar Convention. NEW INFORMATION: Here, we present the most complete
      dataset on saltmarsh occurrence and extent at the global scale. This dataset
      collates 350,985 individual occurrences of saltmarshes and presents the first
      global estimate of their known extent. The dataset captures locational and
      contextual data for saltmarsh in 99 countries worldwide. A total of 5,495,089
      hectares of mapped saltmarsh across 43 countries and territories are represented
      in a Geographic Information Systems polygon shapefile. This estimate is at the
      relatively low end of previous estimates (2.2-40 Mha), however, we took the
      conservative approach in the mapping exercise and there are notable areas in
      Canada, Northern Russia, South America and Africa where saltmarshes are known to
      occur that require additional spatial data. Nevertheless, the most extensive
      saltmarsh worldwide are found outside the tropics, notably including the low
      lying, ice-free coasts, bays and estuaries of the North Atlantic which are well
      represented in our global polygon dataset. Therefore, despite the gaps, we
      believe that, while incomplete, our global polygon data cover many of the
      important areas in Europe, the USA and Australia.

PMID- 28765721
TI  - On the diversity and richness of understory bryophytes at Nectandra Cloud Forest
      Reserve, Costa Rica.
AB  - BACKGROUND: A survey of the understory bryophytes in the Nectandra Cloud Forest
      Preserve yielded 1083 specimens distributed among 55 families, represented by 74
      genera of mosses, 75 genera of liverworts and 3 of hornworts. We studied and
      analyzed the bryophytic distribution on six types of substrates: 1) corticolous,
      2) epiphyllous, 3) saxicolous, 4) terricolous, 5) aquatic and 6) lignicolous. The
      richness and composition of bryophyte genera are compared to those of other
      previous bryophyte surveys from 4 other sites with different oceanic exposures,
      climatic and geographic conditions in Costa Rica. NEW INFORMATION: This is a
      report of the first extensive general survey of bryophytes at the Nectandra
      Reserve, a premontane cloud forest located on the Atlantic slope of Costa Rica,
      an area much less studied compared to the Monteverde cloud forest on the Pacific
      slope.

PMID- 28765722
TI  - Megafauna of the UKSRL exploration contract area and eastern Clarion-Clipperton
      Zone in the Pacific Ocean: Echinodermata.
AB  - BACKGROUND: There is growing interest in mining polymetallic nodules from the
      abyssal Clarion-Clipperton Zone (CCZ) in the tropical Pacific Ocean. Despite
      being the focus of environmental studies for decades, the benthic megafauna of
      the CCZ remain poorly known. In order to predict and manage the environmental
      impacts of mining in the CCZ, baseline knowledge of the megafauna is essential.
      The ABYSSLINE Project has conducted benthic biological baseline surveys in the UK
      Seabed Resources Ltd polymetallic-nodule exploration contract area (UK-1). Prior
      to these research cruises in 2013 and 2015, no biological studies had been done
      in this area of the eastern CCZ. NEW INFORMATION: Using a Remotely Operated
      Vehicle and Autonomous Underwater Vehicle, the megafauna within the UKSRL
      exploration contract area (UK-1) and at a site ~250 km east of the UK-1 area were
      surveyed, allowing us to make the first estimates of megafaunal morphospecies
      richness from the imagery collected. Here, we present an atlas of the abyssal
      echinoderm megafauna observed and collected during the ABYSSLINE cruises to the
      UK-1 polymetallic-nodule exploration contract area in the CCZ. There appear to be
      at least 62 distinct morphospecies (13 Asteroidea, 5 Crinoidea, 9 Echinoidea, 29
      Holothuroidea and 6 Ophiuroidea) identified mostly by imagery but also using
      molecular barcoding for a limited number of animals that were collected. This
      atlas will aid the synthesis of megafaunal presence/absence data collected by
      contractors, scientists and other stakeholders undertaking work in the CCZ,
      ultimately helping to decipher the biogeography of the megafauna in this
      threatened habitat.

PMID- 28765723
TI  - Repatriation Data: More than two million species occurrence records added to the
      Brazilian Biodiversity Information Facility Repository (SiBBr).
AB  - BACKGROUND: Primary biodiversity data records, available on-line, are essential
      for conservation planning. Of the mega diversity countries, Brazil have reached a
      high level of scientific research in describing their biodiversity. However,
      there still remain significant limitations in recovering, collating and
      organizing available information on Brazil's biological diversity and its
      distribution. Since the colonial period, biological material were often collected
      and transferred to other countries, which were characterized, stored and
      maintained. As a result, natural history museums worldwide possess large amounts
      of primary biodiversity data originally from Brazil which are then published on
      line in the international Global Biodiversity Information Facility (GBIF)
      infrastructure. Aiming to recover these data, the Brazilian Biodiversity
      Information System (SiBBr) developed an automatic repatriation tool capable of
      retrieving all records registered in Brazil but published outside Brazilian
      territory in an automated manner. NEW INFORMATION: Thus, 2,459,366 records were
      added to SiBBr's Repository in one day. Europe and the United States hold about
      80% of all records. The data set covers all life kingdoms. Animalia is the most
      represented group with 3 main phylum's: Chordata, Arthropoda and Mollusca, within
      more than 40% of all records. Plantae also comprises a large portion of the
      records with angiosperms having the major number of entries.

PMID- 28765724
TI  - Additions to the knowledge of Nevada carabid beetles (Coleoptera: Carabidae) and
      a preliminary list of carabids from the Great Basin National Park.
AB  - BACKGROUND: Additions to the list of Carabidae known for Nevada, USA and carabid
      beetles found in the Great Basin National Park, NV are reported with notes on
      ecology and identification resources. NEW INFORMATION: For 79 species of
      carabids, we present 57 new state records, two state records previously reported
      in online resources, one confirmation of a previous questionable record for the
      state, and report 22 records for the Great Basin National Park that includes
      three new state records.

PMID- 28765725
TI  - An Online Database of the Immatures of Coleoptera (Arthopoda, Insecta) Described
      from Brazil.
AB  - BACKGROUND: An online database of the described immature beetles from Brazil is
      presented for the first time based on published literature. The main purpose of
      this online database is to ensure accessibility to data associated with the
      described immature Coleoptera from Brazil, which will be useful for future
      biological, ecological, conservational and biogeographical studies. NEW
      INFORMATION: More than 9,486 specimens of 248 genera, 282 species and 4
      subspecies of 76 Coleoptera families from 15 states and the Federal District of
      Brazil were found. Taxonomical and ecological information about each species,
      when available, are given. The dataset of Immatures of Coleoptera described from
      Brazil are available and can be accessed through the portals of GBIF at
      http://www.gbif.org/dataset/8e0e9330-e1b2-475a-9891-4fa8e5c6f57f and the SiBBr at
      http://ipt.sibbr.gov.br/sibbr/resource?r=coleoptera_immature_of_brazil.

PMID- 28765726
TI  - A new species, first report of a male and new distributional records for three
      species of Pteroptrix (Hymenoptera: Aphelinidae) from China.
AB  - BACKGROUND: The Chinese fauna of Pteroptrix currently includes 26 species, of
      wihich 19 species were described originally as new from China: 2 by Howard
      (1907), 2 by Compere (1953), 1 by Flanders (1966), 1 by Viggiani and Ren (1986),
      4 by Huang (1991), 4 by Huang et al. (1992), 1 by Viggiani and Ren (1993), 4 by
      Huang (1994). NEW INFORMATION: Pteroptrix pedicellatasp. n. is described in
      detail and illustrated; the male of P. processa (Huang) is reported for the first
      time. New distributional data for three species, P. leptocera (Huang), P.
      orientalis (Silvestri) and P. processa (Huang), are also provided from China.

PMID- 28765727
TI  - DNA barcoding the fishes of Lizard Island (Great Barrier Reef).

PMID- 28765728
TI  - Automated assembly of a reference taxonomy for phylogenetic data synthesis.

PMID- 28765729
TI  - New species records of Culicoides biting midges (Diptera: Ceratopogonidae) for
      the state of Rondonia in Brazilian Amazon.
AB  - BACKGROUND: Culicoides biting midges are small insects that are proven vectors of
      pathogens that cause disease in animals and humans. There are 1,368 species of
      Culicoides in the world, including 149 species in Brazil and 122 species in the
      Brazilian Amazon Basin. This study documents specimens that were collected
      between 2013 and 2015 in the municipalities of Alvorada d'Oeste, Buritis, Cacoal,
      Costa Marques, Espigao d'Oeste, Guajara-Mirim, Pimenta Bueno, Porto Velho and Sao
      Francisco Guapore. Collections were performed using HP light traps in forest,
      pasture and peridomicilie environments. NEW INFORMATION: Species newly recorded
      in Rondonia State include Culicoides carpenteri Wirth & Blanton, 1953; C.
      dasyophrus Macfie, 1940; C. eublepharus Macfie, 1948; C. galindoi Wirth &
      Blanton, 1953; C. heliconiae Fox & Hoffman, 1944; and C. ignacioi Forattini,
      1957. This is the first record in Brazil of C. darlingtonae Wirth & Blanton,
      1971.

PMID- 28765730
TI  - The Classification and Management Strategy of Spontaneous Isolated Superior
      Mesenteric Artery Dissection.
AB  - Spontaneous isolated superior mesenteric artery dissection (SISMAD) is an
      uncommon but potentially catastrophic pathology. Multiple classification schemes
      have been proposed for this occurrence. Although no consensus has emerged
      regarding which classification should be used, Li's classification scheme is more
      precise and complete compared to other classification systems and can be used to
      guide the treatment of SISMAD. Initial conservative treatment is promising, with
      favorable early and long-term outcomes for most patients; endovascular treatment
      is recommended for patients with persistent/recurrent symptoms after conservative
      treatment; surgical treatment should be performed without delay for patients with
      arterial rupture, intestinal necrosis, or failed endovascular treatment.

PMID- 28765732
TI  - The J Curve Phenomenon is Still Valid in the Era of Primary Revascularization.

PMID- 28765731
TI  - Combining Potent Statin Therapy with Other Drugs to Optimize Simultaneous
      Cardiovascular and Metabolic Benefits while Minimizing Adverse Events.
AB  - Hypercholesterolemia and hypertension are among the most important risk factors
      for cardiovascular (CV) disease. They are also important contributors to
      metabolic diseases including diabetes that further increase CV risk. Updated
      guidelines emphasize targeted reduction of overall CV risks but do not explicitly
      incorporate potential adverse metabolic outcomes that also influence CV health.
      Hypercholesterolemia and hypertension have synergistic deleterious effects on
      interrelated insulin resistance and endothelial dysfunction. Dysregulation of the
      renin-angiotensin system is an important pathophysiological mechanism linking
      insulin resistance and endothelial dysfunction to atherogenesis. Statins are the
      reference standard treatment to prevent CV disease in patients with
      hypercholesterolemia. Statins work best for secondary CV prevention.
      Unfortunately, most statin therapies dose-dependently cause insulin resistance,
      increase new onset diabetes risk and exacerbate existing type 2 diabetes
      mellitus. Pravastatin is often too weak to achieve target low-density lipoprotein
      cholesterol levels despite having beneficial metabolic actions. Renin-angiotensin
      system inhibitors improve both endothelial dysfunction and insulin resistance in
      addition to controlling blood pressure. In this regard, combined statin-based and
      renin-angiotensin system (RAS) inhibitor therapies demonstrate
      additive/synergistic beneficial effects on endothelial dysfunction, insulin
      resistance, and other metabolic parameters in addition to lowering both
      cholesterol levels and blood pressure. This combined therapy simultaneously
      reduces CV events when compared to either drug type used as monotherapy. This is
      mediated by both separate and interrelated mechanisms. Therefore, statin-based
      therapy combined with RAS inhibitors is important for developing optimal
      management strategies in patients with hypertension, hypercholesterolemia,
      diabetes, metabolic syndrome, or obesity. This combined therapy can help prevent
      or treat CV disease while minimizing adverse metabolic consequences.

PMID- 28765733
TI  - Markers for Catheter Ablation of Atrioventricular Accessory Pathways.

PMID- 28765734
TI  - Long-Term Outcome of Kawasaki Disease Complicated by a Large Coronary Aneurysm.

PMID- 28765736
TI  - Factors Influencing the Quality of Standardized Treatment for Patients with Post
      Cardiac Arrest Syndrome.
AB  - BACKGROUND AND OBJECTIVES: For the present study, we investigated the factors
      that influence the quality of standardized treatment for patients with post
      cardiac arrest syndrome (PCAS) to improve the quality of PCAS treatment. SUBJECTS
      AND METHODS: We collected data on patients with cardiac arrest (CA) who were
      admitted to the intensive care units (ICUs) of 11 hospitals-Class II Grade A or
      above-in Suzhou from January to October 2013. Indexes of standardized treatment
      were observed within 72 hrs of CA. We analyzed monitoring techniques, monitoring
      frequency, ICU human and material resources, and intensivists' knowledge of PCAS
      treatment to explore how those factors affected the management of patients with
      PCAS. RESULTS: The bed/nurse ratio and the frequency with which core temperature
      was recorded correlated closely with the implementation of therapeutic
      hypothermia (TH) within 6 hrs of CA. The bed/doctor ratio and intensivists'
      knowledge about PCAS correlated closely with high-quality blood glucose control
      within 6 hrs of CA. Furthermore, the frequency with which core temperature was
      recorded was an independent factor influencing the quality of TH implementation,
      and the number times blood gas was analyzed was an independent factor influencing
      how well partial pressure of carbon dioxide was kept within the normal range in
      the 6 hrs after CA. CONCLUSION: The frequency of core temperature measurements
      and the number of times blood gas is analyzed are the most important factors
      influencing the quality of standardized treatment for patients with PCAS.

PMID- 28765735
TI  - Blood Pressure Targets and Clinical Outcomes in Patients with Acute Myocardial
      Infarction.
AB  - BACKGROUND AND OBJECTIVES: The optimal blood pressure (BP) target in patients
      with a history of acute myocardial infarction (MI) remains as a subject of
      debate. The 'J curve phenomenon' has been suggested as a target for BP control,
      however, it is unclear whether this phenomenon can be applied to MI patients. We
      analyzed patients with acute MI and investigated whether the 'J curve phenomenon'
      exists in this population. SUBJECTS AND METHODS: Data were obtained from a
      nationwide prospective Korea Acute Myocardial Infarction Registry, which included
      10337 patients with acute MI who underwent percutaneous coronary intervention
      (PCI) between 2011 and 2014. The patients were divided into quintiles according
      to systolic blood pressure (SBP) and diastolic blood pressure (DBP), which were
      measured during a two-year clinical follow up. Two-year cumulative incidence of
      major adverse cardiac events (MACE) was analyzed among the groups. RESULTS: MACE
      was defined as a composite of cardiac death, need for recurrent revascularization
      (repeated PCI or coronary arterial bypass graft due to recurrent anginal symptoms
      or reoccurrence of MI), ischemic cerebrovascular accident, and need for
      hospitalization due to heart failure. During the two-year follow up, the total
      cumulative incidence of MACE was 9.7% (n=1005). BP-MACE analysis showed a U
      shaped curve for both SBP and DBP, with the lowest MACE rate in quintiles with an
      average SBP of 112.2 mmHg and DBP of 73.3 mmHg. On Cox regression analysis, the U
      shaped relation was statistically significant. CONCLUSION: In patients with acute
      MI, a 'U curve phenomenon' was observed when assessing patient BP control versus
      MACE rate.

PMID- 28765737
TI  - Local Atrial/Ventricular Ratio as an Adjuvant Marker for Catheter Ablation of
      Atrioventricular Accessory Pathways.
AB  - BACKGROUND AND OBJECTIVES: The earliest atrial (A)/ventricular (V) activation
      potential, or accessory pathway (AP) potential are commonly used as ablation
      targets for atrioventricular (AV) APs. However, these targets are sometimes
      ambiguous. SUBJECTS AND METHODS: We reviewed 119 catheter ablation cases in 112
      patients diagnosed with orthodromic atrioventricular reentrant tachycardia (AVRT)
      or Wolff-Parkinson-White (WPW) syndrome. Local A/V amplitude potentials with the
      earliest activation or AP potential were measured shortly before achieving
      antegrade AP conduction block, ventriculoatrial block during right ventricle (RV)
      pacing, or AVRT termination with no AP conduction. RESULTS: APs were located in
      the left lateral (55.5%), left posterior (17.6%), left posteroseptal (10.1%),
      midseptal (1.7%), right posteroseptal (7.6%), right posterior (1.7%), and right
      lateral (5.9%) regions. The mean earliest activation time was 16.7+/-15.5 ms,
      mean A/V potential was 1.1+/-0.9/1.0+/-0.9 mV, and mean A/V ratio was 1.7+/-2.0.
      There was no statistically significant difference between the activation methods
      (antegrade vs. RV pacing vs. orthodromic AVRT) or AP locations (left vs. right
      atrium). However, when the local A/V ratio was divided into 3 groups (<=0.6,
      1.0+/-0.3, and >=1.4), the antegrade approach resulted in an A/V ratio greater
      than 1.0+/-0.3 (86.7%, p=0.007), and the orthodromic AVRT state resulted in a
      ratio of less than 1.0+/-0.3 (87.5%, p<0.001). CONCLUSION: The mean local A/V
      potential and ratio did not differ by activation method or AP location. However,
      a different A/V ratio based on activation method (>=1.0+/-0.3, antegrade
      approach; and <=1.0+/-0.3, orthodromic AVRT state) could be a good adjuvant
      marker for targeting AV APs.

PMID- 28765738
TI  - Baseline Characteristics of a Retrospective Patient Cohort in the Korean Vascular
      Intervention Society Endovascular Therapy in Lower Limb Artery Diseases (K-VIS
      ELLA) Registry.
AB  - BACKGROUND AND OBJECTIVES: The Korean Vascular Intervention Society Endovascular
      Therapy in Lower Limb Artery Diseases (K-VIS ELLA) Registry is a multicenter
      observational study with retrospective and prospective cohorts of patients with
      lower extremity peripheral artery disease (PAD) undergoing endovascular
      treatment. In this study, we report the baseline characteristics of this
      retrospective cohort. SUBJECTS AND METHODS: In the present study we analyzed
      datasets of 3073 patients with 3972 target limbs from a retrospective cohort
      treated with endovascular therapy in 31 Korean hospitals. Data regarding patient
      baseline clinical and lesion characteristics and postintervention medications
      were collected from electronic medical records. RESULTS: The mean patient age was
      68.3+/-9.4 years. The majority were male (82.1%) with comorbidities such as
      diabetes mellitus (58.0%), hypertension (73.4%), and coronary artery disease
      (CAD; 55.3%). Patients more commonly presented with intermittent claudication
      (66.3%) than with critical limb ischemia (CLI; 33.7%). Femoropopliteal artery
      (41.2%) was the most common target vessel for endovascular treatment, followed by
      the aortoiliac (35.6%) and infrapopliteal arteries (23.2%). TransAtlantic Inter
      Society Consensus for the Management of Peripheral Artery Disease (TASC II) type
      C/D aortoiliac (48.0%) or femoropopliteal lesions (60.2%) were frequent targets
      of endovascular treatment. At hospital discharge, only 73.1% of patients received
      dual antiplatelet therapy and 69.2% received a statin. CONCLUSION: The majority
      of Korean patients with PAD exhibited conventional risk factors, such as male
      sex, older age, diabetes, and hypertension with coexisting CAD. Complex lesions
      were frequently treated with endovascular therapy. However, the rate of adherence
      to guidelines regarding post-procedural medical treatment requires improvement.

PMID- 28765739
TI  - Increased Arterial Stiffness in Behcet's Disease: a Systematic Review and Meta
      Analysis.
AB  - BACKGROUND AND OBJECTIVES: Behcet's disease (BD) is a systemic vasculitis that is
      characterized by genital, oral, or skin lesions, uveitis, and vascular
      complications. Studies have shown that increased arterial stiffness is common in
      systemic immune and inflammatory diseases such as rheumatoid arthritis and
      systemic lupus erythematosus. However, current research has not yet determined
      whether patients with BD have increased arterial stiffness. This meta-analysis
      compares arterial stiffness parameters in subjects with a BD diagnosis to normal
      subjects. SUBJECTS AND METHODS: A comprehensive search of the MEDLINE and EMBASE
      databases was performed from the database beginning through May 2016. Observation
      studies were included in this analysis if they assessed the association between
      BD and arterial stiffness in adult subjects. BD patients met the International
      Study Group criteria for a diagnosis of Behcet's disease. Aortic stiffness was
      assessed using carotid-femoral pulse wave velocity (PWV) measurements as an
      indicator. Pooled mean difference (MD) of PWV and 95% confidence intervals (CI)
      were calculated using a random-effect, generic inverse variance meta-analysis.
      The between-study heterogeneity of effect-size was quantified using the Q
      statistic and I2. RESULTS: Data were extracted from four observational studies
      that included 303 subjects. PWV is significantly higher in patients with Behcet's
      disease compared with controls (MD=0.74;95%, CI: 0.28-1.20, p=0.002, I2=63%).
      CONCLUSION: In this meta-analysis, we observed that PWV, an ideal indicator of
      arterial stiffness, is increased in patients with Behcet's disease compared with
      the controls. Prospective studies in a large population should be done to
      determine the pathophysiological and prognostic implications of increased
      arterial stiffness in BD.

PMID- 28765740
TI  - Aortic Flow Propagation Velocity in Patients with Familial Mediterranean Fever:
      an Observational Study.
AB  - BACKGROUND AND OBJECTIVES: Systemic inflammation has an important role in the
      initiation of atherosclerosis, which is associated with arterial stiffness (AS).
      Aortic flow propagation velocity (APV) is a new echocardiographic parameter of
      aortic stiffness. The relationship between systemic inflammation and AS has not
      yet been described in patients with familial Mediterranean fever (FMF). We aimed
      to investigate the early markers of AS in patients with FMF by measuring APV and
      carotid intima-media thickness (CIMT). SUBJECTS AND METHODS: Sixty-one FMF
      patients (43 women; mean age 27.3+/-6.7 years) in an attack-free period and 57
      healthy individuals (36 women; mean age 28.8+/-7.1 years) were included in this
      study. The individuals with atherosclerotic risk factors were excluded from the
      study. The flow propagation velocity of the descending aorta and CIMT were
      measured to assess AS. RESULTS: APV was significantly lower (60.2+/-16.5 vs.
      89.5+/-11.6 cm/sec, p<0.001) and CIMT was significantly higher (0.49+/-0.09 vs.
      0.40+/-0.10 mm, p<0.001) in the FMF group compared to the control group. There
      were significant correlations between APV and mean CIMT (r=-0.424, p<0.001),
      erythrocyte sedimentation rate (ESR) (r=-0.198, p=0.032), and left ventricle
      ejection fraction (r=0.201, p=0.029). APV and the ESR were independent predictors
      of FMF in logistic regression analysis (OR=-0.900, 95% CI=0.865-0.936, p<0.001
      and OR=-1.078, 95% CI=1.024-1.135, p=0.004, respectively). Mean CIMT and LVEF
      were independent factors associated with APV in linear regression analysis (beta=
      0.423, p<0.001 and beta=0.199, p=0.017, respectively). CONCLUSION: We
      demonstrated that APV was lower in FMF patients and is related to CIMT. According
      to our results, APV may be an independent predictor of FMF.

PMID- 28765741
TI  - Experience with Mechanical Circulatory Support for Medically Intractable Low
      Cardiac Output in a Pediatric Intensive Care Unit.
AB  - BACKGROUND AND OBJECTIVES: Mechanical circulatory support with extracorporeal
      membrane oxygenation (ECMO) and ventricular assist device has always been the
      optimal choice for treating the majority of medically intractable low cardiac
      output case. We retrospectively investigated our institution's outcomes and
      variables associated with a high risk of mortality. SUBJECTS AND METHODS: From
      1999 to 2014, 86 patients who were of pediatric age or had grown-up congenital
      heart disease underwent mechanical circulatory support for medically intractable
      low cardiac output in our pediatric intensive care unit. Of these, 9 grown-up
      congenital heart disease patients were over 18 years of age, and the median age
      of the subject group was 5.82 years (range: 1 day to 41.6 years). A review of all
      demographic, clinical, and surgical data and survival analysis were performed.
      RESULTS: A total of 45 (52.3%) patients were successfully weaned from the
      mechanical assist device, and 25 (29.1%) survivors were able to be discharged.
      There was no significant difference in results between patients over 18 years and
      under 18 years of age. Risk factors for mortality were younger age (<30 days),
      functional single ventricle anatomy, support after cardiac operations, longer
      support duration, and deteriorated pre-ECMO status (severe metabolic acidosis and
      increased levels of lactate, creatinine, bilirubin, or liver enzyme). The
      survival rate has improved since 2010 (from 25% before 2010 to 35% after 2010),
      when we introduced an upgraded oxygenator, activated heart transplantation, and
      also began to apply ECMO before the end-stage of cardiac dysfunction, even though
      we could not reveal significant correlations between survival rate and changed
      strategies associated with ECMO. CONCLUSION: Mechanical circulatory support has
      played a critical role and has had a dramatic effect on survival in patients with
      medically intractable heart failure, particularly in recent years. Meticulous
      monitoring of acid-base status, laboratory findings, and early and liberal
      applications are recommended to improve outcomes without critical complication
      rates, particularly in neonates with single ventricle physiology.

PMID- 28765742
TI  - Clinical Characteristics and Independent Factors Related to Long-Term Outcomes in
      Patients with Left Isomerism.
AB  - BACKGROUND AND OBJECTIVES: We studied the results of patient management for left
      isomerism (LI) and sought to determine factors that may influence survival and
      prognosis. SUBJECTS AND METHODS: We reviewed the medical records of 76 patients
      who were compatible with LI criteria between 1982 and 2014. RESULTS: Of the total
      study population, 29 patients (38.1%) had functional univentricular heart
      disease, 43 patients (56.5%) had cardiac anomalies suitable for biventricular
      hearts, and four patients (5.2%) had normal heart structure. Extracardiac
      anomalies were noted in 38.1% of the study population, including biliary atresia
      in 7.8% of all patients. Of the 25 patients who underwent Kawashima procedures,
      24.0% developed pulmonary arteriovenous fistulas (PAVFs). During the median
      follow-up period of 11.4 years (range: 1 day to 32 years), 14 patients died. The
      10-year, 20-year, and 30-year survival rates were 87%, 84%, and 76%,
      respectively. Preoperative dysrhythmia and uncorrected atrioventricular valve
      regurgitation were significantly associated with late death. There was no
      significant difference in the number of surgical procedures and in survival
      expectancy between patients in the functional single-ventricle group and in the
      biventricular group. However, late mortality was higher in functional single
      ventricle patients after 18 years of age. CONCLUSION: Patients with LI need to be
      carefully followed, not only for late cardiovascular problems such as
      dysrhythmia, valve regurgitation, and the development of PAVFs, but also for
      noncardiac systemic manifestations.

PMID- 28765743
TI  - Outcomes Associated with the Off-label Use of Medical Devices in Congenital Heart
      Disease at a Single Institute.
AB  - BACKGROUND AND OBJECTIVES: While the off-label use of implantable medical devices
      for treating congenital heart disease is not uncommon, the present conditions and
      outcomes of their off-label use have rarely been described. Therefore, this study
      evaluated the prevalence and results of using implantable devices off-label to
      treat congenital heart disease at a single institute. SUBJECTS AND METHODS: This
      was a retrospective study based on the medical records of catheter-based
      interventions for congenital heart disease performed from July 1, 1995 to June 1,
      2015. The inclusion criterion was the off-label use of an implantable device.
      Patient demographic data, procedural success, and follow-up status regarding late
      complications were investigated, and the results of the off-label use of each
      device were compared. RESULTS: Off-label use occurred in 144 of 1730
      interventions with device implantation, accounting for 8.3% of the interventions.
      The median patient age and mean body weight were 51.0 months and 16.3 kg,
      respectively. Immediate and late failures were found in 9 cases, and 3 cases of
      mortality were not directly related to the devices used. The overall success rate
      was 93.8%. There were no long-term complications of the off-label use of
      occlusion devices. No procedural failures resulted from stent implantation, but
      one case of stent malposition and two cases of stent fracture were identified
      after procedure completion. CONCLUSION: In general, the off-label use of
      implantable devices for treating congenital heart disease is safe and effective.

PMID- 28765744
TI  - Long-Term Prognosis for Patients with Kawasaki Disease Complicated by Large
      Coronary Aneurysm (diameter >=6 mm).
AB  - BACKGROUND AND OBJECTIVES: Some patients with Kawasaki disease (KD) develop large
      coronary aneurysms and subsequent coronary stenosis or obstruction, leading to
      ischemic heart disease. This study examined the long-term outcomes of patients
      with KD complicated by large coronary aneurysms. SUBJECTS AND METHODS: The
      medical records of 71 patients (53 men and 18 women) diagnosed with large
      coronary aneurysms (diameter >=6 mm) between December 1986 and December 2013 were
      retrospectively reviewed from our institutional database. RESULTS: The mean age
      at onset was 4.6+/-3.3 years, and the mean follow-up duration was 12.5+/-6.9
      years. Maximum coronary artery internal diameter ranged from 6.1 to 25 mm. Giant
      coronary aneurysms occurred in 48 patients and coronary aneurysms 6-8 mm in
      diameter developed in 23 patients. Coronary stenosis and/or complete occlusion
      occurred in 30 patients (42.3%). Catheter and/or surgical interventions (mean:
      1.5 interventions, range: 1-5 interventions) were performed in 20 patients
      (28.2%), 9 months to 18 years after KD onset, resulting in 33.7% cumulative
      coronary intervention rates at 20 years after onset. There were no differences in
      cumulative coronary intervention rates between two coronary aneurysm groups (6-8
      mm vs. >=8 mm). Myocardial infarction occurred in 7 patients with a giant
      aneurysm and there was one death. CONCLUSIONS: Long-term survival of patients
      with KD complicated by large coronary aneurysm was good even though 28.2% of
      patients underwent multiple catheter or surgical interventions. Careful follow-up
      is also necessary in KD patients with coronary aneurysms 6-8 mm in diameter, such
      as those with giant aneurysms.

PMID- 28765745
TI  - Rapid and Potent Antiarrhythmic Effect of Cardiac Resynchronization Therapy in a
      Patient with Advanced Dilated Cardiomyopathy and a Large Ventricular Arrhythmia
      Burden.
AB  - We report a case demonstrating a rapid and potent antiarrhythmic effect of
      biventricular pacing. A 67-year-old male patient with dilated cardiomyopathy was
      admitted for heart failure. The initial surface electrocardiogram revealed a left
      bundle branch block with a QRS complex duration of 200 ms. Echocardiographic
      examination revealed a left ventricular ejection fraction of 16%, a left
      ventricular end-diastolic dimension of 91 mm, and marked interventricular
      dyssynchrony. Continuous rhythm monitoring revealed frequently-recurring non
      sustained monomorphic ventricular tachycardia (VT). Polymorphic VT, which
      persisted for 27 seconds, occurred on the third day after admission, and the R on
      T phenomenon recurred every two to three days thereafter. Optimal medical therapy
      for four weeks failed to suppress the recurrence of ventricular arrhythmias or
      ameliorate heart failure. Cardiac resynchronization therapy was initiated for an
      anticipated antiarrhythmic effect of biventricular pacing. Three days after the
      initiation of biventricular pacing, the ventricular arrhythmias disappeared
      almost completely.

PMID- 28765747
TI  - Severe Leakage Presenting Mitral Regurgitation Caused by a Pseudoaneurysm
      Connecting the Left Ventricle and the Left Atrium Through Fistulae as a Rare
      Complication of Cardiac Trauma.

PMID- 28765746
TI  - Controlled Atrial Fibrillation after Pulmonary Vein Stenting.
AB  - When there is no pulmonary vein reconnection after catheter ablation for atrial
      fibrillation, patients can experience recurrence of atrial fibrillation without
      clear evidence of non-pulmonary vein foci. We describe a patient with significant
      pulmonary vein stenosis and recurrent atrial fibrillation after four ablation
      procedures. After successful pulmonary vein stenting, the symptoms were resolved,
      and sinus rhythm was maintained for 2 years without treatment with antiarrhythmic
      medication. We believe pulmonary vein stenting potentially controlled atrial
      fibrillation by providing pulmonary vein pressure relief or by compressing the
      epicardial triggers occurring at the pulmonary vein ostium.

PMID- 28765748
TI  - Catheter Ablation of Peri-Conduit Ventricular Tachycardia in a Patient with
      Rastelli Procedure for Double Outlet Right Ventricle with Malposition of Great
      Arteries.

PMID- 28765749
TI  - Grasping the Pseudo-Cleft in the Case of a Small, Severely Tethered Posterior
      Mitral Leaflet.

PMID- 28765750
TI  - Bioptome Perforation at Superior Vena Cava Anastomosis Site in Transplanted
      Heart.

PMID- 28765751
TI  - Erratum: Cardiomyopathies with Mixed and Inapparent Morphological Features in
      Cardiac Troponin I3 Mutation.
AB  - [This corrects the article on p. 413 in vol. 47, PMID: 28567093.].

PMID- 28765752
TI  - Erratum: The Practice Pattern of Percutaneous Coronary Intervention in Korea:
      Based on Year 2014 Cohort of Korean Percutaneous Coronary Intervention (K-PCI)
      Registry.
AB  - [This corrects the article on p. 320 in vol. 47, PMID: 28567082.].

PMID- 28765753
TI  - Adenosine-guided radiofrequency catheter ablation of atrial fibrillation: A meta
      analysis of randomized control trials.
AB  - BACKGROUND: The prognostic significance of adenosine-mediated dormant pulmonary
      vein conduction, and whether such dormant conduction should be eliminated,
      remains controversial. We sought to perform a meta-analysis of data from eligible
      studies to delineate the prognostic impact of adenosine-guided radiofrequency
      catheter ablation of atrial fibrillation. METHODS: A systematic literature search
      was performed using online databases in order to identify relevant studies from
      January 2004 to September 2016. Ten studies [six observational and four
      randomized control trials (RCTs)] were included in the analysis. RESULTS: Five
      studies (two observational and three RCTs) compared the efficacy of adenosine
      mediated elimination of dormant conduction versus no adenosine test. Overall, the
      adenosine-guided ablation strategy displayed better long-term outcomes as
      compared with no adenosine testing (RR 1.08, 95% CI 1.01-1.14, p=0.02;
      Heterogeneity: I2=42%, p: 0.14). The meta-analysis of only RCTs failed to show
      any differences between the two strategies (RR 1.03, 95% CI 0.96-1.11, p=0.37;
      Heterogeneity: I2 0%, p: 0.41). Eight studies (five observational and three RCTs)
      addressed the efficacy of adenosine-induced dormant conduction and additional
      ablation versus no dormant conduction during adenosine challenge. Overall, a
      trend towards a better outcome in those without dormant conduction during drug
      challenge was noted (RR 0.89, 95% CI 0.77-1.03, p=0.11; Heterogeneity: I2 65% p:
      0.006). The pooled analysis of RCTs failed to show any differences between the
      two arms (RR 0.90, 95% CI 0.62-1.30, p= 0.57; Heterogeneity: I2 88%, p: 0.0002).
      CONCLUSIONS: Adenosine-guided radiofrequency catheter ablation of atrial
      fibrillation does not provide additional benefit in terms of freedom of
      arrhythmia recurrence.

PMID- 28765754
TI  - Radiofrequency catheter ablation is effective for atrial fibrillation patients
      with hypertrophic cardiomyopathy by decreasing left atrial pressure.
AB  - BACKGROUND: Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF)
      refractory to medical therapy remains controversial in patients with hypertrophic
      cardiomyopathy (HCM); the acute effects on the direct left atrial (LA) pressure
      are not completely understood. METHODS: We consecutively studied patients with
      HCM (n=15) and without HCM (NHCM, n=106) who underwent extensive encircling
      pulmonary vein isolation for drug-refractory AF. We compared clinical parameters,
      echocardiographic parameters, electrophysiological parameters, LA pressures using
      hemodynamic catheterization and recurrence rate in both groups. RESULTS: The LA
      volume index was significantly higher (51.9+/-13.6 mL/m2 vs. 41.6+/-12.7 mL/m2,
      p=0.02) in the HCM group than the NHCM group. The pre-ablation mean LA pressure
      was significantly higher in the HCM group than the NHCM group. Among the AF
      patients, the mean LA pressure decreased more significantly in the HCM group than
      the NHCM group (post-ablation minus pre-ablation pressures: 4.2+/-3.7 mmHg vs.
      0.9+/-4.1 mmHg, p=0.03). The early recurrence rate (within 30 days after
      ablation) tended to be higher in the HCM group than the NHCM group (20% vs. 5.7%,
      p=0.08), but the rates of late recurrences (>30 days after ablation) were similar
      (13.3% vs. 7.6%, p=0.83). Discontinuation of antiarrhythmic drugs occurred at
      rates of 13% and 62% in the HCM and NHCM groups, respectively (p<0.001).
      CONCLUSIONS: The LA pressure in the HCM group decreased immediately after AF
      RFCA. Patients with HCM and drug-refractory AF may benefit from RFCA.

PMID- 28765755
TI  - Airway support using a pediatric intubation tube in adult patients with atrial
      fibrillation: A simple and unique method to prevent heart movement during
      catheter ablation under continuous deep sedation.
AB  - BACKGROUND: The present study aimed to elucidate the safety and effectiveness of
      a noble and unique airway management technique in which a pediatric intubation
      tube is used in adult patients with atrial fibrillation (AF) undergoing catheter
      ablation (CA) under continuous deep sedation. METHODS: In total, 246 consecutive
      patients with AF (mean age, 65+/-10 years; 60 women) underwent CA under
      dexmedetomidine-based continuous deep sedation. A 4-mm pediatric intubation tube
      guided by a 10-French intratracheal suction tube was inserted smoothly, and the
      tip of the tube was located at the base of the epiglottis. The maximum shifting
      distance of the heart (MSDH) was measured with the 3D mapping system (Ensite NavX
      system) before and after inserting the pediatric intubation tube. RESULTS: At
      baseline, the MSDH of patients under continuous deep sedation was 23+/-14 mm. The
      pediatric intubation tube reduced the MSDH to 13+/-6 mm (mean reduction from
      baseline, 38.4+/-21.7%; P<0.0001). In contrast, oxygen saturation was
      significantly increased from 89+/-8% to 95+/-3% (P<0.0001). The mean distance
      between the nostril and base of the epiglottis was 16.6+/-0.5 mm. Major
      periprocedural complications occurred in 9 (3.6%) patients including 3 (1.2%)
      cardiac tamponade and 6 (2.4%) phrenic nerve injury cases. Larger MSDH (odds
      ratio, 1.13; 95% confidence interval, 1.04-1.25; P=0.007) was a significant
      predictor of major periprocedural complications. No major airway complications
      occurred, except in 3 patients (1.2%) who had minor nasal bleeding. CONCLUSION:
      This unique airway management technique using a pediatric intubation tube for CA
      procedures performed in adult patients with AF under continuous deep sedation was
      easy, safe, and effective.

PMID- 28765756
TI  - Wavefront direction and cycle length affect left atrial electrogram amplitude.
AB  - BACKGROUND: The relationship between atrial electrogram (EGM) characteristics in
      atrial fibrillation (AF) and those in sinus rhythm (SR) are generally unknown.
      The activation rate and direction may affect EGM characteristics. We examined
      characteristics of left atrial (LA) EGMs obtained during pacing from different
      sites. METHODS: The study included 10 patients undergoing pulmonary vein
      isolation for AF. Atrial EGMs were recorded from a 64-pole basket catheter placed
      in the LA, and bipolar EGM amplitudes from the distal electrode pair (1-2) and
      proximal electrode pair (6-7) from 8 splines were averaged. The high right atrium
      (HRA), proximal coronary sinus (CSp), and distal coronary sinus (CSd) were paced
      at 600 ms and 300 ms. RESULTS: When the LA voltage at SR was >=1.5 mV, bipolar
      voltages of the HRA were greater than those of the CSp, which were greater than
      those of the CSd, regardless of the pacing cycle length. The shorter pacing cycle
      length resulted in a reduction of the LA EGM voltage at sites of SR voltage >=1.5
      mV, but no significant difference was seen at sites where the SR EGM amplitude
      was between >0.5 and <1.5 mV. No significant differences were seen in intra
      basket conduction times between pacing cycle lengths of 600 ms and 300 ms at any
      pacing site. CONCLUSION: The rate and direction-dependent reduction of the
      amplitude of atrial EGMs may explain, in part, the voltage discordance during SR
      and AF.

PMID- 28765757
TI  - Vagal response in cryoballoon ablation of atrial fibrillation and autonomic
      nervous system: Utility of epicardial adipose tissue location.
AB  - BACKGROUND: Mechanism and effects of vagal response (VR) during cryoballoon
      ablation procedure on the cardiac autonomic nervous system (ANS) are unclear. The
      present study aimed to evaluate the relationship between VR during cryoballoon
      catheter ablation for atrial fibrillation and ANS modulation by evaluating
      epicardial adipose tissue (EAT) locations and heart rate variability (HRV)
      analysis. METHODS: Forty-one patients with paroxysmal atrial fibrillation (11
      with VR during the procedure and 30 without VR) who underwent second-generation
      cryoballoon ablation were included. EAT locations and changes in HRV parameters
      were compared between the VR and non-VR groups, using Holter monitoring before
      ablation, immediately after ablation and one month after ablation. RESULTS: The
      total EAT volume surrounding the left atrium (LA) in the VR and non-VR groups was
      29.0+/-18.4 cm3 vs 27.7+/-19.7 cm3, respectively (p=0.847). The VR group
      exhibited greater EAT volume overlaying the LA-left superior pulmonary vein (PV)
      junction (6.1+/-3.6 cm3 vs 3.6+/-3.3 cm3, p=0.039) than the non-VR group. HRV
      parameters similarly changed following ablation in both the groups. EAT volume
      overlaying LA-right superior PV junction was significantly correlated with the
      relative changes in root-mean-square successive differences (r=-0.317, p=0.043)
      and high frequency (r=-0.331, p=0.034), immediately after the ablation.
      CONCLUSIONS: Changes in HRV parameters following ablation were similarly observed
      in both the groups. EAT volume on the LA-PV junction is helpful for
      interpretation of VR occurrence and ANS modulation.

PMID- 28765758
TI  - Clinical benefits of deep sedation with a supraglottic airway while monitoring
      the bispectral index during catheter ablation of atrial fibrillation.
AB  - BACKGROUND: Pulmonary vein antrum isolation (PVAI) under sedation has proven to
      be a useful strategy for catheter ablation of atrial fibrillation (AF). METHODS:
      To evaluate the clinical benefits of respiratory management using supraglottic
      airways (SGAs) under deep sedation while monitoring the bispectral (BIS) index
      during the PVAI and the durations from admission to the catheterization room to
      starting the radiofrequency energy delivery (Time alpha), and from starting the
      radiofrequency energy delivery to completion of the PVAI (Time beta), X-ray time,
      frequency of dislocations of the three-dimensional maps (D3DM), procedure-related
      complications, and proportion of an AF-free rate 15 months after the PVAI (PAFFR)
      in patients who received deep sedation without SGAs (Group A: n=48) and those
      with SGAs (Group B: n=51) were evaluated. RESULTS: There were no significant
      differences in patient characteristics, Time alpha (77+/-3 versus 78+/-2 min;
      p=0.816), complications of cardiac tamponade (2% versus 2%; p=0.966), or PAFFR
      (81% versus 88%; p=0.313) between the two groups. However, the Time beta (84+/-4
      versus 67+/-3; p=0.001), X-ray time (53+/-2 versus 34+/-2; p<0.001), and minor
      complications of nasal bleeding (25% versus 0%; p=0.001) were significantly
      shorter and lower in Group B than in Group A, in accordance with a reduction in
      the hypoxia (15% versus 0%; p=0.007) and D3DM (31% versus 8%; p=0.003).
      CONCLUSIONS: These results may demonstrate the clinical benefits of deep sedation
      with SGAs while monitoring the BIS index without any hypoxia during PVAI in
      patients with AF.

PMID- 28765759
TI  - Current use of direct oral anticoagulants for atrial fibrillation in Japan:
      Findings from the SAKURA AF Registry.
AB  - BACKGROUND: Large-scale investigations on the use of oral anticoagulants
      including direct oral anticoagulants (DOACs) in patients with atrial fibrillation
      (AF) have not included Japanese patients. METHODS: We established the multicenter
      SAKURA AF Registry to support prospective observational research on the status of
      anticoagulation treatment, especially with DOAC, for AF in Japan. We enrolled
      3266 AF patients treated with warfarin (n=1577) or any of 4 DOACs (n=1689) from
      63 institutions (2 cardiovascular centers, 13 affiliated hospitals or community
      hospitals, and 48 private clinics) in the Tokyo area. RESULTS: We conducted our
      first analysis of the registry data, and although we found equivalent mean age
      between the DOAC and warfarin users (71.8+/-9.5 vs. 72.3+/-9.4 years, p=0.2117),
      we found a slightly lower risk of stroke (CHADS2 score of 0 or 1 [46.9% vs.
      39.4%, p<0.0001]) and significantly better creatinine clearance in DOAC users
      (70.4+/-27 vs. 65.6+/-25.7 mL/min, p<0.0001). Importantly, we documented under
      dosing in 32% of warfarin users and inappropriate-low-dosing in 19.7-27.6% of
      DOAC users. CONCLUSIONS: Our initial analysis of the SAKURA AF Registry data
      clarified the real-world use of anticoagulants, which includes DOACs and warfarin
      in Japan. The DOAC users were at a lower risk for stroke than the warfarin users.
      In 20-30% of DOAC users, the dose was inappropriately reduced.

PMID- 28765760
TI  - Study design of GENERAL (general practitioners and embolism prevention in NVAF
      patients treated with rivaroxaban: Real-life evidence): A multicenter prospective
      cohort study in primary care physicians to investigate the effectiveness and
      safety of rivaroxaban in Japanese patients with NVAF.
AB  - BACKGROUND: Rivaroxaban, a direct oral anticoagulant (DOAC), has become available
      for stroke prevention in patients with non-valular atrial fibrillation (NVAF).
      However, little is known about its effectiveness and safety when prescribed by
      general practitioners in real-life settings. METHODS: GENERAL is a multicenter,
      prospective, non-interventional observational study of patients receiving
      rivaroxaban for NVAF in daily clinical practice prescribed specifically by
      general practitioners. The target number of participating medical institutions is
      500-700 clinics with fewer than 20 beds and the target number of participants is
      5000. The baseline clinical data, including antidementia medication and frailty,
      and follow-up data including concomitant treatment and outcomes until September
      2018 (maximum three years) will be collected. The primary efficacy endpoints will
      be stroke and/or systemic embolism and the secondary endpoints will be major
      bleeding meeting the ISTH guidelines, non-major and clinically relevant bleeding,
      onset of symptomatic stroke (ischemic/hemorrhagic), systemic embolism, deep vein
      thrombosis/pulmonary thromboembolism, myocardial infarction and/or cardiovascular
      death, and systemic embolism. Based on the provided information, the event
      assessment committee will investigate the endpoint-related events. The annual
      incidence and predictive factors for primary/secondary endpoint will be
      investigated based on underlying disease, age, renal function, and CHADS2,
      CHA2DS2-VASC, and HAS-BLED scores using Cox regression. We will also compare the
      incidence of the primary/secondary endpoint between the present study, EXPAND
      study, and FUSHIMI AF registry study. RESULTS: The results of this study are
      currently under investigation. CONCLUSION: This study will provide important
      information regarding the effectiveness and safety of rivaroxaban treatment in
      Japanese patients with NVAF among general practitioners.

PMID- 28765761
TI  - Simulation of ventricular rate control during atrial fibrillation using ionic
      channel blockers.
AB  - BACKGROUND: The atrioventricular (AV) node is the only compartment that conducts
      an electrical impulse between the atria and the ventricles. The main role of the
      AV node is to facilitate efficient pumping by conducting excitation slowly
      between the two chambers as well as reduce the ventricular rate during atrial
      fibrillation (AF). METHODS: Using computer simulations, we investigated
      excitation conduction from the right atrium to the bundle of His during high-rate
      atrial excitation with or without partial blocking of the calcium or potassium
      ionic current. RESULTS: Our simulations revealed differences in rate reduction
      and repolarization effects between calcium and potassium current blocking and
      high degree of potassium current blocking required to reduce the ventricular rate
      during AF. CONCLUSIONS: Our simulation results explain why potassium current
      blockers are not recommended for controlling ventricular rate during AF.

PMID- 28765762
TI  - Paroxysmal atrial fibrillation recurrences and quality of life in symptomatic
      patients: A crossover study of flecainide and pilsicainide.
AB  - BACKGROUND: The therapeutic goals of atrial fibrillation (AF) patients are to
      reduce symptoms and prevent severe complications associated with AF. This study
      compared the efficacy of flecainide versus pilsicainide in reducing the frequency
      of AF and improving quality of life (QOL) in symptomatic paroxysmal AF patients
      without structural heart disease. METHODS: The Atrial Fibrillation and Quality Of
      Life (AF-QOL) study was a prospective, multicenter, randomized, open-label
      crossover study that compared flecainide and pilsicainide as antiarrhythmic drug
      therapy. Patients were randomized to receive 3 months of treatment with
      flecainide twice daily or pilsicainide 3 times daily. Each treatment consisted of
      a dose-finding phase (weeks 1-4) and an efficacy phase (weeks 5-12). Forty-three
      patients completed the trial. The main outcome was the number of days with
      documented AF episodes using a patient-operated electrocardiogram. QOL
      questionnaires (SF-36 and AF-specific QOL scores) were also completed. RESULTS:
      The median (range) AF frequencies (days/8 weeks) were 2 (0-50) in the flecainide
      treatment group and 1 (0-54) in the pilsicainide treatment group (no significant
      between-group difference). No significant difference in the first recurrence of
      AF during the efficacy phase was noted between flecainide and pilsicainide
      treatments. The frequency and severity scores of AF-related symptoms improved
      from baseline to the end of the treatment periods. No significant differences in
      SF-36 or AF-related QOL scores were noted between the treatment groups.
      CONCLUSIONS: This study found no difference in AF frequency or QOL between
      symptomatic paroxysmal AF patients who received flecainide or pilsicainide.

PMID- 28765763
TI  - Elongated ascending aorta predicts a short distance between his-bundle potential
      recording site and coronary sinus ostium.
AB  - BACKGROUND: When performing catheter ablation of atrioventricular nodal reentrant
      tachycardia (AVNRT), it can be difficult to maintain a safe distance from the His
      recording site to avoid AV block in patients with a short distance between this
      recording site to the coronary sinus (CS) ostium (small triangle of Koch [TOK]).
      In this study, we sought to identify parameters predicting small TOK and test
      these parameters in patients undergoing AVNRT catheter ablation. METHODS: Twenty
      eight patients who underwent catheter ablation of atrial fibrillation using a
      three-dimensional (3D) electroanatomical mapping system (EAM) with computed
      tomography (CT) merge (23 males; mean age, 65.8+/-12.1 years) were included. The
      shortest distance between the CS ostium and His recording sites (His-CSd) was
      measured on the EAM. Aortic (Ao) unfolding in chest X-ray scan, Ao angle to the
      LV, Ao length, Ao to the right ventricular distance, size of the Valsalva in the
      CT scan, and parameters of echocardiogram were evaluated. The identified
      parameters were subsequently tested as predictors for small TOK in patients
      undergoing AVNRT ablation. RESULTS: The size of TOK was associated with Ao length
      (r = -0.70, p<0.01), left ventricular end-systolic dimension (LVDs) (r = -0.51,
      p<0.01), and Ao unfolding. In patients with AVNRT, only Ao unfolding predicted a
      smaller TOK. CONCLUSIONS: Small TOK was associated with longer Ao, larger LVDs,
      and Ao unfolding. Of these, Ao unfolding was associated with smaller TOK in
      patients with AVNRT.

PMID- 28765764
TI  - Focal ablation for atrial tachycardia from the double-exit of the Marshall bundle
      inducing atrial fibrillation.
AB  - Atrial fibrillation (AF) from the ligament/vein of Marshall (LOM/VOM) has
      previously been described. We report the case of a 23-year-old woman with an
      antiarrhythmic drug-resistant AF induced by two distinct atrial tachycardias
      (ATs). Focal ablation of these ATs from the double-exit of the Marshall bundle
      using a three-dimensional map eliminated AF triggering, even though pulmonary
      vein electrical isolation is the cornerstone for paroxysmal AF. Such mechanisms
      are important as triggering factors to plan ablation for paroxysmal AF. Focal
      ablation for triggering and inducing AF, originating from the double-exit of the
      Marshall bundle may be effective in eliminating AF in young patients.

PMID- 28765765
TI  - High-resolution mapping and ablation of recurrent left lateral accessory pathway
      conduction.
AB  - Proper localization of the anatomical target during ablation of the accessory
      pathways (AP) and the ability to detect clear AP potentials on the ablation
      catheter are crucial for successful AP ablation. We report a case of recurring AP
      conduction that was finally eliminated using a novel ablation catheter equipped
      with high-resolution mini-electrodes. Smaller and closer electrodes result in
      high mapping resolution with less signal averaging and cancellation effects.
      Owing to improved sensitivity, the new catheter seems effective in detecting
      fragmented and high frequency signals, thus allowing more effective
      radiofrequency application and improving ablation success.

PMID- 28765766
TI  - Asystole in focal epilepsy complicating a traumatic subdural hematoma.
AB  - Ictal asystole due to sinus node suppression is a cause of sudden unexplained
      death in epilepsy. Here, for the first time, we describe a complete
      atrioventricular nodal block in a patient with non-compressive traumatic subdural
      hematoma, who developed ictal asystole as a delayed presentation. A leadless VVI
      pacemaker (ventricular paced, ventricular sensed, and pacing inhibited in
      response to a sensed beat) was implanted as a preventive measure against seizure
      related heart block.

PMID- 28765767
TI  - Simple and effective solution for diaphragm pacing by that uses the transvenous
      femoral approach in a patient treated with cardiac resynchronization
      defibrillator therapy: The wrapping method.
AB  - The use of cardiac resynchronization therapy (CRT) has become widespread in
      patients with heart failure who meet the criteria for implantation. Coronary
      sinus lead positioning is important to provide the intended biventricular
      stimulation. Diaphragm pacing is a lead-related complication which occurs
      secondary to phrenic nerve stimulation. We present the case of a 58-year-old male
      patient who had diaphragm pacing after CRT with defibrillator implantation. The
      complication was resolved by using the transvenous femoral approach with the
      wrapping method.

PMID- 28765768
TI  - Subacute pneumothorax contralateral to the venous access site associated with
      atrial lead perforation in a patient who was receiving corticosteroid therapy.
AB  - Pneumothorax contralateral to the venous access site due to the right atrial lead
      is an uncommon complication. Concomitant steroid use is known as a risk factor of
      pacemaker lead perforation. We report a rare case of subacute contralateral
      pneumothorax due to a screw-in atrial lead perforation that occurred after dual
      chamber pacemaker implantation in a patient who was receiving steroid therapy.
      The pneumothorax disappeared, and no recurrence was observed during follow-up
      with close observation alone.

PMID- 28765769
TI  - Initial experience with the subcutaneous implantable cardioverter-defibrillator
      in a single Japanese center.
AB  - BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is
      recognized as a viable alternative to the transvenous ICD. The safety and
      efficacy of this device has been demonstrated in Western countries, but studies
      with S-ICD implantation in Japanese patients have not been reported. METHODS AND
      RESULTS: Twelve patients received an S-ICD implant in our institute between
      February and September 2016. All S-ICDs were successfully implanted without
      complications. One appropriate and one inappropriate therapy was identified.
      CONCLUSIONS: S-ICD implantation appears to provide a viable alternative to
      transvenous ICD implantation for some Japanese patients. However, we should
      perform careful follow-up of patients to eliminate inappropriate therapy.

PMID- 28765770
TI  - The tachycardia that outsmarted the SMART.

PMID- 28765772
TI  - Anti-inflammatory effects of Nelumbo leaf extracts and identification of their
      metabolites.
AB  - BACKGROUND/OBJECTIVES: Nelumbo leaves have been used in traditional medicine to
      treat bleeding, gastritis, hemorrhoids, and halitosis. However, their mechanisms
      have not been elucidated. MATERIALS/METHODS: The present study prepared two
      Nelumbo leaf extracts (NLEs) using water or 50% ethanol. Inflammatory response
      was induced with LPS treatment, and expression of pro-inflammatory mediators
      (inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-alpha
      (TNF-alpha), interleukin (IL)-1beta, and IL-6 and nitric oxide (NO) and
      prostaglandin E2 (PGE2) productions were assessed. To determine the anti
      inflammatory mechanism of NLEs, we measured nuclear factor-kappaB (NF-kappaB)
      activity. Major metabolites of NLEs were also analyzed and quantified. RESULTS:
      NLEs effectively reduced the expression and productions of pro-inflammatory
      mediators such as IL-1beta, IL-6, TNF-alpha, PGE2, and NO. NLEs also reduced NF
      kappaB activity by inhibiting inhibitor of NF-kappaB phosphorylation. Both
      extracts contained catechin and quercetin, bioactive compounds of NLEs.
      CONCLUSIONS: In this study, we showed that NLEs could be used to inhibit NF
      kappaB-mediated inflammatory responses. In addition, our data support the idea
      that NLEs can ameliorate disease conditions involving chronic inflammation.

PMID- 28765773
TI  - Astaxanthin induces migration in human skin keratinocytes via Rac1 activation and
      RhoA inhibition.
AB  - BACKGROUND/OBJECTIVES: Re-epithelialization has an important role in skin wound
      healing. Astaxanthin (ASX), a carotenoid found in crustaceans including shrimp,
      crab, and salmon, has been widely used for skin protection. Therefore, we
      investigated the effects of ASX on proliferation and migration of human skin
      keratinocyte cells and explored the mechanism associated with that migration.
      MATERIAL/METHOD: HaCaT keratinocyte cells were exposed to 0.25-1 ug/mL of ASX.
      Proliferation of keratinocytes was analyzed by using MTT assays and flow
      cytometry. Keratinocyte migration was determined by using a scratch wound-healing
      assay. A mechanism for regulation of migration was explored via
      immunocytochemistry and western blot analysis. RESULTS: Our results suggest that
      ASX produces no significant toxicity in human keratinocyte cells. Cell-cycle
      analysis on ASX-treated keratinocytes demonstrated a significant increase in
      keratinocyte cell proliferation at the S phase. In addition, ASX increased
      keratinocyte motility across the wound space in a time-dependent manner. The
      mechanism by which ASX increased keratinocyte migration was associated with
      induction of filopodia and formation of lamellipodia, as well as with increased
      Cdc42 and Rac1 activation and decreased RhoA activation. CONCLUSIONS: ASX
      stimulates the migration of keratinocytes through Cdc42, Rac1 activation and RhoA
      inhibition. ASX has a positive role in the re-epithelialization of wounds. Our
      results may encourage further in vivo and clinical study into the development of
      ASX as a potential agent for wound repair.

PMID- 28765774
TI  - Increase in dietary protein content exacerbates colonic inflammation and
      tumorigenesis in azoxymethane-induced mouse colon carcinogenesis.
AB  - BACKGROUND/OBJECTIVE: The incidence of colorectal cancer (CRC) has been
      attributed to higher intake of fat and protein. However, reports on the
      relationship between protein intake and CRC are inconsistent, possibly due to the
      complexity of diet composition. In this study, we addressed a question whether
      alteration of protein intake is independently associated with colonic
      inflammation and colon carcinogenesis. MATERIALS/METHODS: Balb/c mice were
      randomly divided into 4 experimental groups: 20% protein (control, 20P, 20%
      casein/kg diet), 10% protein (10P, 10% casein/kg diet), 30% protein (30P, 30%
      casein/kg diet), and 50% protein (50P, 50% casein/kg diet) diet groups and were
      subjected to azoxymethane-dextran sodium sulfate induced colon carcinogenesis.
      RESULTS: As the protein content of the diet increased, clinical signs of colitis
      including loss of body weight, rectal bleeding, change in stool consistency, and
      shortening of the colon were worsened. This was associated with a significant
      decrease in the survival rate of the mice, an increase in proinflammatory protein
      expression in the colon, and an increase in mucosal cell proliferation. Further,
      colon tumor multiplicity was dramatically increased in the 30P (318%) and 50P
      (438%) groups compared with the control (20P) group. CONCLUSIONS: These results
      suggest that a high protein diet stimulates colon tumor formation by increasing
      colonic inflammation and proliferation.

PMID- 28765775
TI  - Monocyte chemoattractant protein-1 polymorphism interaction with spirulina
      immunomodulatory effects in healthy Korean elderly: A 16 week, double-blind
      randomized clinical trial.
AB  - BACKGROUND/OBJECTIVES: Spirulina is a known a functional food related to lipid
      profiles, immune functions, and antioxidant capacity. Circulating monocyte
      chemoattractant protein-1 (MCP-1) level is associated with inflammation markers.
      Single nucleotide polymorphism in the MCP-1 promoter region -2518 have been
      identified and shown to affect gene transcription. Gene variation may also impact
      functional food supplementary effects. The current study investigated the
      interaction of MCP-1 -2518 polymorphism with spirulina supplements on anti
      inflammatory capacity in Korean elderly. SUBJECTS/METHODS: After genotyping,
      healthy elderly subjects (n = 78) were included in a randomized, double blind,
      and placebo controlled study. Baseline characteristic, body composition, and
      dietary intake were measured twice (baseline vs. week 16). For 16 weeks, subjects
      consumed 8 g either spirulina or placebo daily. Plasma MCP-1, interleukin (IL) 
      2, IL-6, tumor necrosis factor (TNF)-alpha, complement (C) 3, immunoglobulin (Ig)
      G, and Ig A concentrations and lymphocyte proliferation rate (LPR) were analyzed
      as inflammatory markers. RESULTS: In the placebo group with A/A genotype, MCP-1
      level was significantly increased, but the spirulina group with A/A genotype was
      unchanged. IL-2 was significantly increased only in subjects with spirulina
      supplementation. TNF-alpha was significantly reduced in subjects with the G
      carrier. C3 was significantly increased in the placebo group, particularly when
      A/A increased more than G, but not when spirulina was ingested. LPR was
      significantly different only in subjects with A/A genotype; there was a
      significant increase in phytohemagglutinin and lipopolysaccharide induced LPR in
      the spirulina group. CONCLUSION: In healthy Korean elderly, spirulina
      supplementation may influence different inflammatory markers by the MCP-1
      genotype. These results may be useful for customized dietary guidelines to
      improve immune function in Koreans.

PMID- 28765776
TI  - Validation of dietary reference intake equations for estimating energy
      requirements in Korean adults by using the doubly labeled water method.
AB  - BACKGROUND/OBJECTIVES: The doubly labeled water (DLW) method is considered the
      gold standard for the measurement of total energy expenditure (TEE), which serves
      to estimate energy requirements. This study evaluated the accuracy of predictive
      dietary reference intake (DRI) equations for determining the estimated energy
      requirements (EER) of Korean adults by using the DLW as a reference method.
      SUBJECTS/METHODS: Seventy-one participants (35 men and 36 women) aged between 20
      and 49 years were included in the study. The subjects' EER, calculated by using
      the DRI equation (EERDRI), was compared with their TEE measured by the DLW method
      (TEEDLW). RESULTS: The DRI equations for EER underestimated TEE by -36.3 kcal/day
      (-1.3%) in men and -104.5 kcal/day (-4.9%) in women. The percentages of accurate
      predictions among subjects were 77.1% in men and 62.9% in women. There was a
      strong linear correlation between EERDRI and TEEDLW (r=0.783, P<0.001 in men and
      r=0.810, P<0.001 in women). CONCLUSIONS: The present study supports the use of
      DRI prediction equations to determine EER in Korean adults. More studies are
      needed to confirm our results and to assess the validity of these equations in
      other population groups, including children, adolescents, and older adults.

PMID- 28765771
TI  - 2017 consensus of the Asia Pacific Heart Rhythm Society on stroke prevention in
      atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia, causing a 2
      fold increase in mortality and a 5-fold increase in stroke. The Asian population
      is rapidly aging, and in 2050, the estimated population with AF will reach 72
      million, of whom 2.9 million may suffer from AF-associated stroke. Therefore,
      stroke prevention in AF is an urgent issue in Asia. Many innovative advances in
      the management of AF-associated stroke have emerged recently, including new
      scoring systems for predicting stroke and bleeding risks, the development of non
      vitamin K antagonist oral anticoagulants (NOACs), knowledge of their special
      benefits in Asians, and new techniques. The Asia Pacific Heart Rhythm Society
      (APHRS) aimed to update the available information, and appointed the Practice
      Guideline sub-committee to write a consensus statement regarding stroke
      prevention in AF. The Practice Guidelines sub-committee members comprehensively
      reviewed updated information on stroke prevention in AF, emphasizing data on
      NOACs from the Asia Pacific region, and summarized them in this 2017 Consensus of
      the Asia Pacific Heart Rhythm Society on Stroke Prevention in AF. This consensus
      includes details of the updated recommendations, along with their background and
      rationale, focusing on data from the Asia Pacific region. We hope this consensus
      can be a practical tool for cardiologists, neurologists, geriatricians, and
      general practitioners in this region. We fully realize that there are gaps,
      unaddressed questions, and many areas of uncertainty and debate in the current
      knowledge of AF, and the physician's decision remains the most important factor
      in the management of AF.

PMID- 28765777
TI  - Changes in body weight and food security of adult North Korean refugees living in
      South Korea.
AB  - BACKGROUND/OBJECTIVES: Relocation to new environments can have a negative impact
      on health by altering body weight and dietary patterns. This study attempted to
      elucidate changes in body weight, food security, and their current food and
      nutrient consumption in adult North Korean refugees (NKR) living in South Korea
      (SK). SUBJECTS/METHODS: This study analyzed data on 149 adult NKR from a North
      Korean refugee health in SK cohort at four time points (leaving North Korea,
      entering SK, first examination, and second examination). Body weight was self
      reported at the two earlier time points and directly measured at the two later
      time points. Food security, diet-related behaviors (dietary habits and food
      consumption), and sociodemographic information were obtained using a self
      administered questionnaire. Nutrient intake information was obtained by one-day
      24-hour recall. Statistical analyses were performed with SPSS ver 23.0. RESULTS:
      Body weight increased during relocation by an average of 4 kg, although
      diversified patterns were observed during the settlement period in SK.
      Approximately 39.6% of subjects maintained their body weight between the first
      and second examinations, whereas 38.6% gained and 22.1% lost at least 3% of their
      body weight at the first examination by the second examination. Food security
      status improved from 12.1% food secure proportion to 61.7%. NKR showed generally
      good food and nutrient consumption (index of nutrient quality: 0.77-1.93). The
      body weight loss group showed the most irregular meal consumption pattern (P <
      0.05), and eating-out was infrequent in all three groups. Consumption frequencies
      of food groups did not differ by group, except in the fish group (P = 0.036).
      CONCLUSION: This study observed considerable body weight adjustment during the
      settlement period in SK after initial weight gain, whereas food security
      consistently improved. More detailed understanding of this process is needed to
      assist healthy settlement for NKR in SK.

PMID- 28765778
TI  - A randomized controlled trial of an individualized nutrition counseling program
      matched with a transtheoretical model for overweight and obese females in
      Thailand.
AB  - BACKGROUND/OBJECTIVE: Effective weight reduction remains a challenge throughout
      the world as the prevalence of obesity and its consequences are increasing. This
      study aimed to determine the effects of an individualized nutrition counseling
      program (IC) matched with a transtheoretical model (TTM) for overweight and obese
      subjects. SUBJECTS/METHODS: Fifty overweight and obese subjects aged 19-60 years
      with a body mass index >= 23 kg/m2 were enrolled in the weight reduction study.
      They were randomized into two groups: Intervention group received an IC matched
      with a TTM; control group received an educational handbook. Body weight (BW),
      body fat (BF), waist circumference (WC), waist to height ratio (WHtR), stages of
      change (SOC), processes of change (POC), food intake, and physical activity (PA)
      were assessed at baseline and at 4, 8, and 12 weeks after program initiation in
      both groups. All data were analyzed by intention-to-treat, using SPSS software
      for hypothesis testing. RESULTS: Forty-five female subjects were included in the
      12-week trial at Ramkhamhaeng Hospital, Bangkok, Thailand. The results showed
      significant weight loss (1.98 +/- 1.75 kg; 3% loss of initial weight) in the
      intervention group at 12 weeks, compared to a 0.17 +/- 1.67 kg loss in the
      control group. There were significant differences between intervention and
      control groups in BF mass (-1.68 +/- 1.78, -0.04 +/- 1.62 kg); percentage BF (
      1.54 +/- 2.11, 0.08 +/- 2.05); WC (-5.35 +/- 3.84, 0.13 +/- 3.23 cm); WHtR (
      0.0336 +/- 0.02, -0.0004 +/- 0.02), and energy consumption (-405.09 +/- 431.31, 
      74.92 +/- 499.54 kcal/day) in the intervention and control groups, respectively.
      Intragroup SOC was improved in both groups. The POC for the weight management
      action (WMA) process was significantly different with POC scores increasing by
      16.00 +/- 11.73 and 7.74 +/- 14.97 in the intervention and the control groups,
      respectively. PA level did not change in either group. CONCLUSIONS: The IC
      matched with a TTM resulted in reductions in BW, BF, and WC, thus reducing likely
      health risks by decreasing energy intake and inducing positive behavior changes
      while enhancing the WMA process.

PMID- 28765779
TI  - Effects of folic acid supplementation on serum homocysteine levels, lipid
      profiles, and vascular parameters in post-menopausal Korean women with type 2
      diabetes mellitus.
AB  - BACKGROUND/OBJECTIVES: Complications of diabetes, such as cardiovascular disease,
      are associated with increased mortality among type 2 diabetes mellitus patients.
      Homocysteine has been recently identified as a predictor of cardiovascular
      disease-related complications in diabetes. We investigated whether or not
      supplementation with folic acid tablets can lower homocysteine levels and improve
      parameters related with vascular complications. SUBJECTS/METHODS: We conducted a
      non-randomized 8-week trial involving postmenopausal diabetic women (n = 25)
      supplemented with 800 ug of folic acid (400 ug twice a day) daily. Subjects'
      serum levels of folate, homocysteine, and vitamin B12 were measured, along with
      vascular function and brachial-ankle pulse wave velocity. RESULTS: Folic acid
      supplementation significantly increased serum folate levels (P < 0.0001), reduced
      homocysteine levels (P < 0.0001), and increased vitamin B12 levels (P = 0.0063).
      There were significant decreases in low-density lipoprotein cholesterol levels as
      well as the ratios of low-density lipoprotein cholesterol to high-density
      lipoprotein cholesterol and total cholesterol to high-density lipoprotein
      cholesterol. Brachial-ankle pulse wave velocities were not altered by
      supplementation. Changes in serum vitamin B12 after folic acid supplementation
      were negatively correlated with changes in brachial-ankle pulse wave velocity.
      CONCLUSIONS: In this study on postmenopausal Korean women with type 2 diabetes
      mellitus, folic acid supplementation reduced serum homocysteine levels, increased
      serum folate and vitamin B12 levels, and lowered lipid parameters.

PMID- 28765780
TI  - Associations of alcohol consumption and alcohol flush reaction with leukocyte
      telomere length in Korean adults.
AB  - BACKGROUND/OBJECTIVES: Telomere length is a useful biomarker for determining
      general aging status. Some studies have reported an association between alcohol
      consumption and telomere length in a general population; however, it is unclear
      whether the alcohol flush reaction, which is an alcohol-related trait
      predominantly due to acetaldehyde dehydrogenase deficiency, is associated with
      telomere length. This cross-sectional study aimed to evaluate the associations of
      alcohol consumption and alcohol flush reaction with leukocyte telomere length
      (LTL). SUBJECTS/METHODS: The study included 1,803 Korean adults. Participants
      provided blood specimens for LTL measurement assay and reported their alcohol
      drinking status and the presence of an alcohol flush reaction via a questionnaire
      based interview. Relative LTL was determined by using a quantitative polymerase
      chain reaction. Statistical analysis used multiple linear regression models
      stratified by sex and age groups, and potential confounding factors were
      considered. RESULTS: Age-specific analyses showed that heavy alcohol consumption
      (> 30 g/day) was strongly associated with a reduced LTL in participants aged >=
      65 years (P < 0.001) but not in younger participants. Similarly, the alcohol
      flush reaction was associated with a reduced LTL only in older participants who
      consumed > 15 g/day of alcohol (P < 0.01). No significant alcohol consumption or
      alcohol flush reaction associations with LTL were observed in the sex-specific
      analyses. CONCLUSIONS: The results suggest that older alcohol drinkers,
      particularly those with the alcohol flush reaction, may have an accelerated aging
      process.

PMID- 28765781
TI  - Factors affecting vegetable preference in adolescents: stages of change and
      social cognitive theory.
AB  - BACKGROUND/OBJECTIVES: Despite the importance of consuming sufficient amounts of
      vegetables, daily vegetable intake among adolescents in Korea is lower than the
      current dietary recommendation. The objective of this study was to examine
      determinants affecting vegetable preference in order to suggest a stage-tailored
      education strategy that can promote vegetable consumption in adolescents.
      SUBJECTS/METHODS: Adolescents (n = 400, aged 16-17 years) from two high schools
      participated in a cross-sectional study. Survey variables were vegetable
      preference, the social cognitive theory (SCT) and stages of change (SOC)
      constructs. Based on vegetable preference, subjects were classified into two
      groups: a low-preference group (LPG) and a high-preference group (HPG). SOC was
      subdivided into pre-action and action/maintenance stages. To compare SCT
      components and SOC related to vegetable preference, chi-squared and t-tests,
      along with stepwise multiple-regression analysis, were applied. RESULTS: In the
      LPG, a similar number of subjects were classified into each stage. Significant
      differences in self-efficacy, affective attitudes, and vegetable accessibility at
      home and school were detected among the stages. Subjects in the HPG were mainly
      at the maintenance stage (81%), and there were significant differences among the
      stages regarding self-efficacy, affective attitudes, and parenting practice. In
      the predictions of vegetable preference, self-efficacy and parenting practice had
      a significant effect in the "pre-action" stage. In the action/maintenance stage,
      outcome expectation, affective attitudes, and vegetable accessibility at school
      had significant predictive value. In predicting the vegetable preference for all
      subjects, 42.8% of the predictive variance was accounted for by affective
      attitudes, self-efficacy, and vegetable accessibility at school. CONCLUSION: The
      study revealed that different determinants affect adolescent vegetable preference
      in each stage. Self-efficacy and affective attitudes are important determinants
      affecting vegetable preference. Additionally, school-based nutrition intervention
      that focuses on enhancing affective attitudes, self-efficacy, and vegetable
      exposure may constitute an effective education strategy for promoting vegetable
      consumption among adolescents.

PMID- 28765782
TI  - Erratum: Antioxidant mechanism of black garlic extract involving nuclear factor
      erythroid 2-like factor 2 pathway.
AB  - [This corrects the article on p. 206 in vol. 11, PMID: 28584577.].

PMID- 28765783
TI  - Erratum.
AB  - [This corrects the article on p. 2452 in vol. 8, PMID: 27382458.].

PMID- 28765785
TI  - Solitary ulcer in cecum, mimicking a carcinoma: A case report.
AB  - INTRODUCTION: Solitary ulcers in the colon are rare and infrequent; little over
      200 cases have been reported in medical literature. We present a case of a
      patient presenting with a solitary colonic ulcer associated with NSAIDs intake,
      mimicking a malignant lesion. A review of the literature is also revised.
      PRESENTATION OF CASE: 68- year-old female patient with past history of
      nonsteroidal anti-inflammatory drugs (NSAID) intake for chronic pain, complaining
      of severe abdominal pain was admitted to our teaching hospital. The diagnosis of
      a low-grade dysplasia was made with colonoscopy and biopsy, a malignant lesion
      could not be ruled out. A laparoscopy right colectomy was performed without
      complications. The final diagnosis resulted in a solitary cecal ulcer.
      DISCUSSION: The majority of the cases of solitary colonic ulcers occur in the
      ascending colon, at the cecum, which has been attributed mostly to the intake of
      NSAIDs. There could be solitary colonic ulcers in other portions of the large
      intestine, caused by different etiologies: ischemia, inflammatory disease,
      sterocoraceus ulcers, ulcers caused by infections, among other more uncommon
      causes. The diagnosis is often made through a biopsy of the tissue during a
      colonoscopy, with either surgical or conservative care. CONCLUSION: The diagnosis
      of solitary cecal ulcer should be considered in patients presenting with RLQ
      abdominal pain and with history of NSAIDs consumption. Recognition of this
      diagnosis by surgeons, ruling out malignancies, understanding the morphologic
      features, and carefully taking the patient's history are essential for the
      diagnosis and treatment of this uncommon disease.

PMID- 28765786
TI  - A metagenomic survey of forest soil microbial communities more than a decade
      after timber harvesting.
AB  - The scarcity of long-term data on soil microbial communities in the decades
      following timber harvesting limits current understanding of the ecological
      problems associated with maintaining the productivity of managed forests. The
      high complexity of soil communities and the heterogeneity of forest and soil
      necessitates a comprehensive approach to understand the role of microbial
      processes in managed forest ecosystems. Here, we describe a curated collection of
      well replicated, multi-faceted data from eighteen reforested sites in six
      different North American ecozones within the Long-term Soil Productivity (LTSP)
      Study, without detailed analysis of results or discussion. The experiments were
      designed to contrast microbial community composition and function among forest
      soils from harvested treatment plots with varying intensities of organic matter
      removal. The collection includes 724 bacterial (16S) and 658 fungal (ITS2)
      amplicon libraries, 133 shotgun metagenomic libraries as well as stable isotope
      probing amplicon libraries capturing the effects of harvesting on
      hemicellulolytic and cellulolytic populations. This collection serves as a
      foundation for the LTSP Study and other studies of the ecology of forest soil and
      forest disturbance.

PMID- 28765787
TI  - A large-scale solar dynamics observatory image dataset for computer vision
      applications.
AB  - The National Aeronautics Space Agency (NASA) Solar Dynamics Observatory (SDO)
      mission has given us unprecedented insight into the Sun's activity. By capturing
      approximately 70,000 images a day, this mission has created one of the richest
      and biggest repositories of solar image data available to mankind. With such
      massive amounts of information, researchers have been able to produce great
      advances in detecting solar events. In this resource, we compile SDO solar data
      into a single repository in order to provide the computer vision community with a
      standardized and curated large-scale dataset of several hundred thousand solar
      events found on high resolution solar images. This publicly available resource,
      along with the generation source code, will accelerate computer vision research
      on NASA's solar image data by reducing the amount of time spent performing data
      acquisition and curation from the multiple sources we have compiled. By improving
      the quality of the data with thorough curation, we anticipate a wider adoption
      and interest from the computer vision to the solar physics community.

PMID- 28765784
TI  - Tissue expansion for breast reconstruction: Methods and techniques.
AB  - OBJECTIVE: In this work, the authors review recent data on the different methods
      and techniques of TE/implant-based reconstruction to determine the complication
      profiles and the advantages and disadvantages of the different techniques. This
      information will be valuable for surgeons performing breast reconstructions.
      MATERIALS AND METHODS: A thorough literature review was conducted by the authors
      concerning the current strategy of tissue expander (TE)/implant-based breast
      reconstruction following breast cancer surgery. RESULTS: Loss of the breast can
      strongly affect a woman's personal and social life while breast reconstruction
      reduces the sense of mutilation felt by women after a mastectomy, and provides
      psychosocial as well as aesthetic benefits. TE/implant-based reconstruction is
      the most common breast reconstructive strategy, constituting almost 65% of all
      breast reconstructions in the US. Although numerous studies have been published
      on various aspects of alloplastic breast reconstructions, most studies are single
      center observations. No evidence-based guidelines are available as yet.
      Conventional TE/implant-based reconstruction can be performed as a two-stage
      procedure either in the immediate or delayed setting. Moreover, the adjunctive
      use of acellular dermal matrix further broadened the alloplastic breast
      reconstruction indication and also enhanced aesthetic outcomes. CONCLUSIONS:
      TE/implant-based reconstruction has proved to be a safe, cost-effective, and
      reliable technique that can be performed in women with various comorbidities.
      Short operative time, fast recovery, and absence of donor site morbidity are
      other advantages over autologous breast reconstruction.

PMID- 28765788
TI  - A Brazilian case of Bernard-Soulier syndrome with two distinct founder mutations.
AB  - Bernard-Soulier syndrome (BSS) is a rare bleeding disorder of autosomal recessive
      inheritance characterized by macrothrombocytopenia. We report the case of a 14
      year-old girl diagnosed with BSS who is a fourth-generation Brazilian of Japanese
      descent and has a compound heterozygote mutation as the responsible gene. The
      compound heterozygosity would have occurred from the global and long-term racial
      migration that brought about an accidental encounter of two rare mutant alleles
      of different origins.

PMID- 28765789
TI  - Deep sequencing reveals variations in somatic cell mosaic mutations between
      monozygotic twins with discordant psychiatric disease.
AB  - Monozygotic (MZ) twins have been thought to be genetically identical. However,
      recent studies have shown discordant variants between them. We performed whole
      exome sequencing (WES) in five MZ twin pairs with discordant neurodevelopmental
      disorders and one healthy control MZ twin to detect discordant variants. We
      identified three discordant variants confirmed by deep sequencing after analysis
      by personalized next-generation sequencing (NGS). Three mutations in FBXO38
      (chr5:147774428;T>G), SMOC2 (chr6:169051385;A>G) and TDRP (chr8:442616;A>G), were
      detected with low allele frequency of mutant alleles on deep sequencing,
      suggesting that these loci are mosaic due to somatic mutations in a developmental
      stage. Our results suggest that deep sequencing analysis would be an adequate
      method to detect discordant mutations in candidate genes responsible for
      heritable diseases.

PMID- 28765790
TI  - A minimally invasive surgical technique for the management of U-shape sacral
      fractures.
AB  - INTRODUCTION: We present a small case series for the rare U-shape sacral
      fracture. The U-shape sacral fracture is characterised by bilateral longitudinal
      sacral fractures and a transverse sacral fracture through the S2 vertebral body.
      Historically it has been described following falls from a height and a high
      velocity mechanism is often required for this injury. We also describe a surgical
      technique for fixation of U-shape sacral fractures and subsequent implant removal
      6 months post-operatively. CASE PRESENTATION: We present the cases of three
      patients who presented to our institution with this injury. All patients were
      treated with minimally invasive, lumbo-sacro-pelvic (LSP) fixation. One patient
      was lost to follow-up. The remaining two patients had complete resolution of
      neurological function. These two patients had restoration of lumbosacral motion
      after removal of implants and had returned to pre-injury function. DISCUSSION: We
      describe a new technique for treating U-shape sacral fractures which reduces the
      morbidity associated with surgery and maintains lumbosacral motion.

PMID- 28765791
TI  - Coronary artery disease presenting with left upper quadrant pain in a patient
      with chronic cervical tetraplegia.
AB  - INTRODUCTION: This single-subject case report aims to describe and discuss a case
      of a patient with established C5 tetraplegia with acute coronary syndrome
      presenting with left upper quadrant pain and tenderness. CASE PRESENTATION: A 65
      year-old male with chronic C5 American Spinal Injury Association Impairment Scale
      (AIS) A tetraplegia presented to the emergency department with severe left upper
      quadrant pain radiating across the chest to the right upper limb with associated
      dyspnoea and diaphoresis. Prior to his emergency department admission, he had
      experienced progressive worsening of left upper quadrant pain and tenderness over
      several months. He was a non-smoker and swam regularly. He underwent coronary
      angiography and was found to have significant coronary artery disease. Drug
      eluting stents were placed to critical coronary artery lesions followed by an
      uneventful hospital course with complete symptom resolution and discharge home.
      DISCUSSION: Patients with tetraplegia are known to have higher rates of
      cardiovascular disease compared to ambulatory patients. Their cardiovascular risk
      profile may include atypical risk factors, for example, sleep disordered
      breathing, relative immobility and autonomic dysfunction. A high index of
      suspicion for cardiac pathology is warranted in those with cervical tetraplegia
      with persistent 'atypical' symptoms, including within the abdomen (especially
      when no specific abdominal organ dysfunction is evident). Sleep apnoea and
      significantly impaired mobility are potential cardiac risk factors in this
      patient group and should alert the emergency physician to cardiac disease (as in
      this case) irrespective of their complex past medical history and symptomatology.

PMID- 28765792
TI  - Economical synthesis of silver nanoparticles using leaf extract of Acalypha
      hispida and its application in the detection of Mn(II) ions.
AB  - This study was focused on the synthesis of silver nanoparticles using Acalypha
      hispida leaf extract and the characterization of the particles using UV-Vis
      spectroscopy, XRD, FT-IR, and TEM. The results showed the formation of silver
      nanoparticles, crystalline in nature, with an average size of 20-50 nm. The leaf
      extract components were analyzed with GC-MS and exhibited a high content of
      Phytol (40.52%), n-Hexadecanoic acid (9.67%), 1,2,3-Benzenetriol (7.04%), alpha-d
      Mannofuranoside methyl (6.22%), and d-Allose (4.45%). The optimization and
      statistical investigation of reaction parameters were studied and maximum yield
      with suitable properties of silver nanoparticles was obtained at leaf extract
      volume (0.5 mL), the concentration of silver nitrate (1.75 mM), and reaction
      temperature (50  degrees C). The method of detecting Mn2+ ions using the
      colloidal silver nanoparticles was discussed. The minimum and maximum detection
      limit were found to be 50 and 200 uM of Mn(II) ions, respectively. Thus, the
      obtained results encourage the use of economical synthesis of silver
      nanoparticles in the development of nanosensors to detect the pollutants present
      in industrial effluents.

PMID- 28765793
TI  - Infant Botulism in the Very Young Neonate: A Case Series.
AB  - Background  Though botulism is a rare disease overall, all infants younger than 1
      year of age are at risk of contracting infant botulism, the most prevalent form
      reported in the United States. Nonetheless, infant botulism is frequently omitted
      from the differential diagnosis of the very young neonate exclusively due to age,
      and the diagnosis is often only considered secondarily after a costly and
      prolonged work up is undertaken. Delayed diagnosis can lead not only to
      unnecessary testing but also to prolonged hospital stay and increased morbidity.
      Case  This case series highlights three critically ill neonates, all younger than
      30 days, who presented to our neonatal intensive care unit and were eventually
      diagnosed with infant botulism. The initial diagnostic dilemma is described for
      each of these patients and highlights the importance of early recognition of the
      main symptoms, in addition to consideration of important potential coinciding
      conditions.

PMID- 28765794
TI  - Diabetes as an Independent Predictor for Extended Length of Hospital Stay and
      Increased Adverse Post-Operative Events in Patients Treated Surgically for
      Cervical Spondylotic Myelopathy.
AB  - BACKGROUND: Diabetes as an independent driver of peri-operative outcomes, and
      whether its severity impacts indications is conflicted in the research. The
      purpose of this study is to evaluate diabetes as a predictor for postoperative
      outcomes in cervical spondylotic myelopathy (CSM) patients. METHODS: A
      retrospective review was performed of patients treated surgically for CSM (ICD-9
      721.1) from 2010-2012 in the prospectively-collected American College of Surgeons
      National Surgical Quality Improvement Program (NSQIP) database. Outcome measures
      were length of stay, and the presence of complications. Diabetic patients were
      stratified based on whether or not their diabetes was insulin- or non-insulin
      dependent. RESULTS: A total of 5,904 surgical CSM patients were included, 1101
      (19%) had diabetes. 722 (65%) were non-insulin-dependent diabetics, and 381 (35%)
      were insulin-dependent diabetics. Diabetes was found to be an independent
      predictor of extended LOS (OR: 1.878[2.262-1.559], p<0.001) as well as of
      developing a complication (OR: 1.666[2.217-1.253], p<0.001) after controlling for
      associated variables like BMI. Type of diabetes (insulin- vs. non-insulin
      dependent) showed little significant difference between the groups (p>0.05),
      however, patients with insulin-dependent diabetes were associated with an
      increased incidence of wound complications (p=0.027); severity of diabetes was
      not associated with any other individual complications. CONCLUSIONS: Type and
      severity of diabetes is not a predictor for complication. Diabetes is associated
      with extended LOS and peri-operative morbidity. Level of evidence: Class 2b.
      Clinical relevance: Our findings support the view of many spine surgeons, who
      believe that diabetes has a negative impact on the outcome of surgery for CSM.
      Our findings support those cohort studies that found an association between
      diabetes and worst post-operative outcomes following surgical treatment of CSM.
      These findings lend support to the importance of monitoring preoperative serum
      glucose levels, as prevention of peri-operative hyperglycemia has been linked to
      improved postoperative outcomes in spine, joint and colon surgery.

PMID- 28765795
TI  - Inpatient versus Outpatient Anterior Cervical Discectomy and Fusion: A
      Perioperative Complication Analysis of 259,414 Patients From the Healthcare Cost
      and Utilization Project Databases.
AB  - BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is one of the most
      common operations utilized to address pathology of the cervical spine. Few
      reports have attempted to compare complications associated with inpatient versus
      outpatient ACDF. METHODS: The Nationwide Inpatient Sample (NIS) from 2001-2012
      and the State Ambulatory Services Database (SASD) for New Jersey (NJ) from 2003
      2012 were used for analysis. Patients receiving ACDF (defined as anterior
      cervical fusion (ICD-0 code=81.02) + excision of intervertebral disc (80.51))
      were segmented into an inpatient group derived from the NIS, and an outpatient
      group derived from the NJ SASD. Patients receiving > 2 levels fused (ICD-9 codes
      81.63-81.64), or surgery for cancer (ICD-9 codes 140-239), or trauma (ICD-9
      codes=805.0-806.9) were excluded. Propensity score matching (PSM) was used to
      adjust the analysis for patient age, race, sex, primary payer for care, and
      number of medical diagnoses. RESULTS: Of the 94,492,438 inpatients comprising the
      NIS from 2001-2012, 257,398 received ACDF. Of the 4,194,207 outpatients
      comprising the NJ SASD, 2,016 received ACDF. PSM of 10,080 patients (all 2,016
      SASD and 8,064 from NIS) was performed, and subsequent analysis revealed that
      durotomy (P=0.001;OR=0.81), paraplegia, postoperative infection, hematoma/seroma
      (OR=0.14), respiratory complications, acute posthemorrhagic anemia and red blood
      cell transfusion (all P<0.001) were less frequent in outpatient versus inpatient
      ACDF (p<0.05). These results were similar to an unmatched analysis involving all
      of the NIS patients. CONCLUSION: Accepting the limitations of the NIS and SASD
      (inability to distinguish between one and two-level fusions, no long-term follow
      up, potential selection bias, disparities between inpatient and outpatient ACDF
      populations), these findings indicate that for 1-2 level ACDF, perioperative
      complications, including durotomy, paraplegia, hematoma, and acute
      posthemorrhagic anemia were more commonly reported following inpatient ACDF.
      Future studies involving outpatient analysis of several states will be necessary
      to determine whether these results of outpatient ACDF are applicable nationwide.

PMID- 28765796
TI  - The Effects of Topical Vancomycin on Mesenchymal Stem Cells: More May Not Be
      Better.
AB  - BACKGROUND: The use of topical vancomycin is increasingly popular in spine
      surgery. Large retrospective reviews suggest that topical vancomycin provides a
      cost-effective decrease in post-operative infection. Currently, there is little
      that is known about the maximum dose that can be applied locally. When 1 gram of
      vancomycin is mixed into the bone graft and another 1 gram applied freely in a
      spine wound, the local concentration of antibiotic ranges from 260-2900 MUg/mL in
      the immediate post-op period and 50-730 MUg/mL by the second post-operative day.
      We hypothesized that exuberant doses of vancomycin would be toxic to mesenchymal
      stem cells (MSCs). METHODS: Bone marrow was obtained from the femoral canal of
      patients undergoing routine elective total hip arthroplasty. Mesenchymal stem
      cells were isolated using plastic adhesion. Cells were exposed to a wide range of
      doses of vancomycin for 24 hours and then assessed for viability. Osteogenic
      potential was assessed with alizarin red staining. RESULTS: There was dose
      dependent cell death with vancomycin use. MSC death was 9.43% at 400 MUg/mL
      (p=0.047), 13.79% at 1600 MUg/mL (p=0.0047), 19.35% at 3200 MUg/mL (p<0.0001),
      24.82% at 6400 MUg/mL (p<0.0001) and 51.83% at 12800 MUg/mL of vancomycin
      (p<0.0001) in comparison to the control group containing no vancomycin.
      CONCLUSIONS: Our in vitro study suggests that vancomycin has toxic effects on
      hMSCs, a cell population particularly important for bone formation. In the
      absence of any clinical evidence suggesting that "more vancomycin is better," and
      our data suggesting that more vancomycin is harmful in vitro, surgeons electing
      to use topical vancomycin in spine surgery should restrict their use to the doses
      currently reported in the available published studies unless specific reasons
      exist otherwise. This study does not establish a contraindication to the use of
      topical vancomycin, nor does it suggest that pseudarthroses are attributable to
      vancomycin use.

PMID- 28765797
TI  - Radiographic Analysis of Cervical and Spinal Alignment in Multilevel ACDF with
      Lordotic Interbody Device.
AB  - BACKGROUND: Restoration and maintenance of cervical lordosis is an important
      clinical parameter in spine surgery. The purpose of this study was to determine
      the extent to which a multilevel anterior cervical discectomy and fusion (ACDF:
      greater than 3 levels) procedure restores cervical lordosis and the affect of
      increasing lordosis on sagittal vertical axis. METHODS: We performed a
      retrospective radiographic analysis of 69 patients who underwent multilevel ACDF
      by 2 surgeons between 2013 and 2014. We measured the global and segmental
      sagittal alignment of the cervical spine using the cobb method at 4 time
      intervals (preop, post op 4wks, 10wks and 6 months) as well as the sagittal
      vertical axis (SVA) using both a C1-S1 and C7-S1 plumb line methods at 2 time
      intervals (preop and post op 4wks). Radiographs were measured by three reviewers.
      RESULTS: Interrater reliability was good to excellent for all measurements.
      Cervical lordosis significantly increased from preop 10.26 degrees  to 4 weeks
      postop 19.44 degrees  and was maintained up to 6 months 19.34 (p<0.0005).
      Segmental cervical lordosis was also significantly increased from preop 8.22
      degrees  to post op at 4 weeks (20.26 degrees ) and was maintained at post op
      10weeks 20.30 degrees  and post op 6 months 19.56 degrees  (p<0.0005). C7-S1 SVA
      and C1-S1 SVA also significantly increased from 12.04mm preop to 27.49mm post op
      4 wks (p<0.0005) and -1.93mm preop to 8.67mm post op (p<0.0005) respectively. A
      change in C2-C7 lordosis positively correlated with a change in C7-SVA and C1-SVA
      (r=0.37, P<0.005, and r=0.312, p<0.05 respectively). CONCLUSIONS: Multilevel ACDF
      significantly increases and maintains both segmental and global cervical lordosis
      up to 6 months after surgery. Increasing C2-C7 global lordosis is correlated with
      increasing positive sagittal vertical axis. Level of evidence: IV.

PMID- 28765798
TI  - Bilateral C5 Motor Palsy after Anterior Cervical Decompression and Fusion: A Case
      Report and Review of the Literature.
AB  - BACKGROUND: Bilateral C5 motor palsy is a rare but potentially debilitating
      complication after cervical spine decompression with very few reports in the
      published literature. PURPOSE: To present a case of bilateral C5 motor palsy
      after anterior cervical decompression and fusion and discuss the incidence and
      risk factors of this complication. STUDY DESIGN/SETTING: We report a case of a 57
      year-old male who underwent a three level C3-C6 anterior cervical discectomy and
      fusion with instrumentation who developed a postoperative bilateral C5 motor
      palsy. METHODS: A review of the literature was performed regarding reports on and
      incidence of post-operative bilateral C5 palsy following either anterior or
      posterior cervical spine decompression. RESULTS: Bilateral C5 motor palsy is a
      rare complication of cervical spine decompression with an overall incidence of
      0.38%. Although a group of risk factors have been suggested no single cause has
      been identified. CONCLUSIONS: Bilateral C5 motor palsy is a rare but debilitating
      complication of cervical decompression.

PMID- 28765799
TI  - Fortifying the Bone-Implant Interface Part 1: An In Vitro Evaluation of 3D
      Printed and TPS Porous Surfaces.
AB  - BACKGROUND: An aging society and concomitant rise in the incidence of impaired
      bone health have led to the need for advanced osteoconductive spinal implant
      surfaces that promote greater biological fixation (e.g. for interbody fusion
      cages, sacroiliac joint fusion implants, and artificial disc replacements).
      Additive manufacturing, i.e. 3D-printing, may improve bone integration by
      generating biomimetic spinal implant surfaces that mimic bone morphology. Such
      surfaces may foster an enhanced cellular response compared to traditional implant
      surfacing processes. METHODS: This study investigated the response of human
      osteoblasts to additive manufactured (AM) trabecular-like titanium implant
      surfaces compared to traditionally machined base material with titanium plasma
      spray (TPS) coated surfaces, with and without a nanocrystalline hydroxyapatite
      (HA) coating. For TPS-coated discs, wrought Ti6Al4V ELI was machined and TPS
      coating was applied. For AM discs, Ti6Al4V ELI powder was 3D-printed to form a
      solid base and trabecular-like porous surface. The HA-coating was applied via a
      precipitation dip-spin method. Surface porosity, pore size, thickness, and
      hydrophilicity were characterized. Initial cell attachment, proliferation,
      alkaline phosphatase (ALP) activity, and calcium production of hFOB cells (n=5
      per group) were measured. RESULTS: Cells on AM discs exhibited expedited
      proliferative activity. While there were no differences in mean ALP expression
      and calcium production between TPS and AM discs, calcium production on the AM
      discs trended 48% higher than on TPS discs (p=0.07). Overall, HA-coating did not
      further enhance results compared to uncoated TPS and AM discs. CONCLUSIONS:
      Results demonstrate that additive manufacturing allows for controlled trabecular
      like surfaces that promote earlier cell proliferation and trends toward higher
      calcium production than TPS coating. Results further showed that nanocrystalline
      HA may not provide an advantage on porous titanium surfaces. CLINICAL RELEVANCE:
      Additive manufactured porous titanium surfaces may induce a more osteogenic
      environment compared to traditional TPS, and thus present as an attractive
      alternative to TPS-coating for orthopedic spinal implants.

PMID- 28765800
TI  - Fortifying the Bone-Implant Interface Part 2: An In Vivo Evaluation of 3D-Printed
      and TPS-Coated Triangular Implants.
AB  - BACKGROUND: Minimally invasive surgical fusion of the sacroiliac (SI) joint using
      machined solid triangular titanium plasma spray (TPS) coated implants has
      demonstrated positive clinical outcomes in SI joint pain patients. Additive
      manufactured (AM), i.e. 3D-printed, fenestrated triangular titanium implants with
      porous surfaces and bioactive agents, such as nanocrystalline hydroxyapatite (HA)
      or autograft, may further optimize bony fixation and subsequent biomechanical
      stability. METHODS: A bilateral ovine distal femoral defect model was used to
      evaluate the cancellous bone-implant interfaces of TPS-coated and AM implants.
      Four implant groups (n=6/group/time-point) were included: 1)TPS-coated, 2)AM,
      3)AM+HA, and 4)AM+Autograft. The bone-implant interfaces of 6- and 12-week
      specimens were investigated via radiographic, biomechanical, and
      histomorphometric methods. RESULTS: Imaging showed peri-implant bone formation
      around all implants. Push-out testing demonstrated forces greater than 2500 N,
      with no significant differences among groups. While TPS implants failed primarily
      at the bone-implant interface, AM groups failed within bone ~2-3mm away from
      implant surfaces. All implants exhibited bone ongrowth, with no significant
      differences among groups. AM implants had significantly more bone ingrowth into
      their porous surfaces than TPS-coated implants (p<0.0001). Of the three AM
      groups, AM+Auto implants had the greatest bone ingrowth into the porous surface
      and through their core (p<0.002). CONCLUSIONS: Both TPS and AM implants exhibited
      substantial bone ongrowth and ingrowth, with additional bone through growth into
      the AM implants' core. Overall, AM implants experienced significantly more bone
      infiltration compared to TPS implants. While HA-coating did not further enhance
      results, the addition of autograft fostered greater osteointegration for AM
      implants. CLINICAL RELEVANCE: Additive manufactured implants with a porous
      surface provide a highly interconnected porous surface that has comparatively
      greater surface area for bony integration. Results suggest this may prove
      advantageous toward promoting enhanced biomechanical stability compared to TPS
      coated implants for SI joint fusion procedures.

PMID- 28765801
TI  - Regression of Disc-Osteophyte Complexes Following Laminoplasty Versus Laminectomy
      with Fusion for Cervical Spondylotic Myelopathy.
AB  - BACKGROUND: Laminectomy with fusion (LF) and laminoplasty are two posterior-based
      surgical approaches for the surgical treatment of cervical spondylotic myelopathy
      (CSM). The decompressive effect of these approaches is thought to be primarily
      related to the dorsal drift of the spinal cord away from ventral compressive
      structures. A lesser known mechanism of spinal cord decompression following
      cervical LF is regression of the ventral disc osteophyte complexes which is
      postulated to result from the alteration of motion across the fused motion
      segment. The goal of this study was to determine whether regression of the
      ventral disc-osteophyte complexes occur following laminoplasty and compare the
      magnitude of this occurrence to cervical laminectomy and fusion. METHODS: Seventy
      patients with CSM who underwent pre- and postoperative magnetic resonance imaging
      (MRI) and were treated with either laminoplasty or LF. The size of the disc
      osteophyte complex at all operative levels were measured on pre- and
      postoperative MRI using digital calipers. RESULTS: The laminoplasty group
      consisted of 25 patients with an average age of 54.9 and a mean of 3.24 surgical
      levels while the LF group consisted of 45 patients with an average age of 65.4
      and a mean of 3.44 surgical levels (age, p < 0.0001; levels, p= 0.46). The
      average time interval between pre- and post-operative MRI was 16.2 and 15.6
      months in the laminoplasty and LF groups, respectively (p = 0.91). The average
      time interval between surgery and post-operative MRI was 10.1 and 10.7 months in
      the laminoplasty and LF groups, respectively (p = 0.86). When comparing pre- and
      post-operative MRI, there was a 9.59% decrease in disc-osteophyte complex size
      from 3.84mm +/- 0.74 to 3.47mm +/- 0.86 in the laminoplasty group compared to a
      35.4% decrease in disc-osteophyte complex size from 4.60mm +/- 1.06 to 2.98mm +/-
      1.33 in LF group (laminoplasty, p < 0.0001; LF, p = 0.0067). Using logistic
      regression analysis, LF, increased time interval between surgery and post
      operative MRI, high cobb angle, and straight sagittal alignment were all
      independently associated with increased disc-osteophyte complex regression (p <
      0.05). No differences in functional outcomes (as defined by mJOA scores) was
      found between the two surgical techniques. CONCLUSIONS: In patients with CSM that
      had a posterior surgical approach, LF is associated with a larger interval
      regression in disc-osteophyte complex size compared to laminoplasty. This is
      likely related to the loss of motion of the cervical spine after surgery as
      governed by Wolff's law and the Heuter-Volkmann's principle. Although the
      decompressive effect of LF and laminoplasty is primarily related to the dorsal
      drift of the spinal cord away from ventral compressive structures, disc
      osteophyte complex regression likely provides another mechanism of spinal cord
      decompression.

PMID- 28765802
TI  - Clinical Gait Analysis on a Patient Undergoing Surgical Correction of Kyphosis
      from Severe Ankylosing Spondylitis.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease
      primarily affecting the axial skeleton, including the sacroiliac joints,
      costovertebral joints, and the spine. Patients with AS found to have an alter
      gait pattern. The purpose of this study was to investigate biomechanical
      alterations in gait after surgical correction in a patient with severe kyphosis
      from AS. METHODS: A case report in controlled laboratory study, a pretest
      posttest design. A 20 year-old male presented with severe sagittal imbalance and
      inability to stand erect due to AS. He presented with thoracic kyphosis of 70
      degrees , lumbar kyphosis of 25 degrees , and pelvic incidence of 43 degrees .
      The patient had a complex spinal reconstruction with 84 degrees  of sagittal
      correction, normalizing his sagittal alignment. Gait analysis was performed the
      day before surgery and one month post surgery, including three-dimensional
      kinematics, ground reaction forces, and electromyography outcomes. RESULTS:
      Normalization of spinal alignment minimally increased walking speed and cadence.
      Lower extremity ranges of motion angles increased, but were not symmetrical even
      one month post surgery. Postoperatively, trunk flexion, neck extension and head
      orientation angles decreased compared with preoperative values, but was not
      symmetrical even one month post surgery. The trunk muscles were activated earlier
      in the post surgery condition compared to the pre surgery condition while lower
      extremity muscles presented later muscle activation. CONCLUSIONS: Surgical
      correction of spinal alignment improved spine function and efficiency. Changes in
      gait abnormality parameters observed imply that the patient used less energy to
      ambulate after surgery than before surgery. Although pre-surgery data showed
      compensation in the spine kinematics, post-surgery data supported significant
      changes in the spine and the lower extremity values. CLINICAL RELEVANCE: Formal
      gait and motion analysis can provide a method to assess the impact of severe
      spinal deformity on function and changes after treatment.

PMID- 28765804
TI  - Integrated Fixation Cage Loosening Under Fatigue Loading.
AB  - BACKGROUND: Screw loosening is a well-known adverse event in traditional spinal
      fusion instrumentation. This phenomenon may hinder segmental stability of the
      spine leading to bony non-union. In recent years numerous lumbar integrated
      fixation cages (IFC) have been introduced that offer a low profile alternative to
      a standard cage with an anterior plate (AP+C). The fixation approach for IFCs is
      different than a traditional anterior approach; therefore, it is unclear whether
      IFCs may loosen from the surrounding bone over time. The purpose of this study
      was to quantify screw loosening of IFC devices compared to AP+C implants under
      fatigue loading using micro-CT and image processing techniques. METHODS: L2-3 and
      L4-5 functional spinal units (FSUs) were obtained from nine human lumbar spines.
      These FSUs were then reconstructed with either AP+C or IFC implants designed to
      attach to vertebral bodies using four screws (two top and two bottom for AP+C;
      two medial and two lateral for IFC). The reconstructed specimens were fatigued in
      flexion-extension load of +/-3 Nm at 1Hz for first 5,000 cycles and it was
      increased to +/-5 Nm until 20,000 cycles. After removing screws to prevent image
      artifact, micro-CT scans were performed on all FSUs post-fatigue. These images
      were post-processed to calculate three-dimensional volumes around screw holes
      created due to damage at the screw-implant interface. RESULTS: IFC screws had
      significantly greater (p=0.008) screw hole volumes compared to AP+C screws after
      fatigue testing. This increased screw hole volume for IFC devices was mainly due
      to loosening in medial screws. Medial screws had significantly greater (p<0.003)
      screw hole volumes compared to lateral IFC screws and all AP+C screws. There was
      no difference (p>0.888) between the screw hole volumes of lateral IFC, top AP+C,
      and bottom AP+C screws. CONCLUSIONS: This study elucidated screw-loosening
      mechanisms in integrated fixation cages under simulated physiological loading. In
      particular, spatial differences in fixation was observed for IFC screws across
      the vertebra where medial screws loosened at a greater frequency compared to
      lateral screws post-fatigue. This novel technique may also be used to
      quantitatively investigate screw fixation post-fatigue testing in a variety of
      spinal devices.

PMID- 28765803
TI  - Most Cited Publications in Cervical Spine Surgery.
AB  - PURPOSE: The purpose of this study is to perform a citation analysis on the most
      frequently cited articles in the topic of cervical spine surgery and report on
      the top 100 most cited publication in this topic. METHODS: We used the Thomson
      Reuters Web of Science to search citations of all articles from 1945 to 2015
      relevant to cervical spine surgery and ranked them according to the number of
      citations. The 100 most cited articles that matched the search criteria were
      further analyzed by number of citations, first author, journal, year of
      publication, country and institution of origin. RESULTS: The top 100 cited
      articles in the topic of cervical spine surgery were published from 1952-2011.
      The number of citations ranged from 106 times for the 100th paper to 1206 times
      for the top paper. The decade of 1990-1999 saw the most publications. The Journal
      of Spine published the most articles, followed by Journal of Bone and Joint
      Surgery America. Investigators from America authored the most papers and The
      University of California contributed the most publications. Cervical spine fusion
      was the most common topic published with 36 papers, followed by surgical
      technique and trauma. CONCLUSION: This article identifies the 100 most cited
      articles in cervical spine surgery. It has provided insight to the history and
      development in cervical spine surgery and many of which have shaped the way we
      practice today.

PMID- 28765805
TI  - Computer Assisted Cobb Angle Measurements: A novel algorithm.
AB  - BACKGROUND: The standard for evaluating scoliosis is PA radiographs using Cobb
      angle to measure curve magnitude. Newer PACS systems allow easier Cobb angle
      calculations, but have not improved inter/intra observer precision of
      measurement. Cobb angle and its progression are important to determine treatment;
      therefore, angle variability is not optimal. This study seeks to demonstrate that
      a performance equivalent to that achieved in the manual method is possible using
      a novel computer algorithm with limited user input. The authors compared Cobb
      angles from predetermined spinal levels in the average attending score versus the
      computer assisted approach. METHODS: Retrospective analysis of PA radiographs
      from 58 patients previously evaluated for scoliosis was collected. Predesignated
      spinal levels (e.g., T2-T10) were assigned for different curves and calculated by
      Cobb method. Four spine surgeons evaluated these Cobb angles. Their average
      scores were measured and compared to formulated values using the novel computer
      based algorithm. Literature reports inter-observer reliability is 6.3-7.2degrees.
      Limits of accuracy were set at 5 degrees of average orthopedic surgeons' score.
      RESULTS: The computer-based algorithm calculated Cobb angles within 5 degrees of
      orthopedic surgeons' average with a standard deviation of 3.2 degrees. This
      result was based on a 95% confidence interval with p values <0.001. The computer
      algorithm was plotted against average angle determined by the surgeons, with
      individual determinations and linear regression (r2 =0.90). The average
      difference between surgeons' measures and computer algorithm was 0.4 degrees(SD=
      3.2degrees, n=79). There was a tendency for the computer algorithm program to
      overestimate the angle at larger angles, but difference was small with r2 = 0.09.
      CONCLUSIONS: Our study showed the novel computer based algorithm was an efficient
      and reliable method to assess scoliotic curvature in the coronal plane with the
      possibility of expediting clinic visits, ensuring reliability of calculation and
      decreasing patient exposure to radiation. Level of Evidence: III.

PMID- 28765806
TI  - Contour and Angle-Function Based Scoliosis Monitoring: Relaxing the Requirement
      on Image Quality in the Measurement of Spinal Curvature.
AB  - PURPOSE: A method for measuring spinal curvature that provides a useful analog to
      the Cobb angle and is tolerant of degraded image quality is proposed.
      Conventional methods require a higher standard of discernibility for vertebra
      features and suffer high variability. METHODS: Assumption is made that the
      natural representation of the spine for the purpose of scoliosis monitoring is
      that of a continuous curved contour rather than a series of discrete vertebral
      bodies with individual orientations. The angle that a tangent line to this
      contour makes with the vertical, expressed as a continuous function of height, is
      proposed as a metric for characterization of the curve. The Cobb angle can be
      approximated as the difference between the extrema of this function, and details
      of the function shape can provide additional markers for tracking curve variation
      and evolution. A method for deriving the angle function from coronal images of
      the spine is proposed, and both manual and automatic variants of the procedure
      are described. RESULTS: The method is applied to conventional coronal radiographs
      and to magnetic resonance (MR) coronal views derived from volumetric acquisitions
      of the spine. Included in the latter category is an image exhibiting poor
      discrimination of vertebra features due to motion artifacts. The method permits
      extraction of the curve and Cobb angles in all cases. CONCLUSIONS: Because the
      spine contour is discernible even in low quality images where vertebral endplates
      may be obscured or poorly contrasted from surrounding tissue, the approach offers
      improved reliability, applicability across imaging modalities, and, in the case
      of x-rays, the possibility of a reduced radiation dose. Moreover, since it relies
      on larger image features and exploits the continuity of the spine, the contour
      based approach is expected to reduce the variability associated with Cobb angle
      measurement.

PMID- 28765807
TI  - The Influence of Lordotic cages on creating Sagittal Balance in the CMIS
      treatment of Adult Spinal Deformity.
AB  - BACKGROUND: CMIS techniques are heavily dependent on placement of lateral
      interbody cages. Cages with an increased lordotic angle are being advocated to
      improve segmental lordosis and SVA. We assessed the segmental lordosis achieved
      with the individual cages. We further studied three variables and the effect each
      had on segmental lordosis: the lordosis angle of the cage, the position of the
      cage in the intervertebral space, and the level that it has been placed. METHODS:
      This is a retrospective study of 66 consecutive patients who underwent lateral
      interbody fusion using lordotic cages as part of CMIS correction of scoliosis
      from June 2012 to January 2016. Standing radiographs at pre op and 6-week follow
      up were reviewed to identify the position of the cage in the intervertebral space
      and the amount of segmental lordosis achieved. RESULTS: A total of 224 cages were
      placed. The 6 degrees , 10 degrees , 12 degrees , and 20 degrees  cages achieved
      a mean segmental lordosis of 9.00 degrees , 13.09 degrees , 13.23 degrees , and
      18.32 degrees , respectively (P < .05). Additionally, cages placed in the
      anterior, middle, and posterior 3rd of the disk space produced 13.02 degrees ,
      11.47 degrees , and 8.23 degrees  of lordosis, respectively (P < .05).
      Stratifying by level, cages placed at T12-L1, L1-2, L2-3, L3-4, and L4-5
      translated to mean segmental lordotic values of 8.43 degrees , 10.02 degrees ,
      11.38 degrees , 12.91 degrees , and 14.58 degrees , respectively (P < .05).
      CONCLUSIONS: The angle of the cage had an impact on segmental lordosis. Achieved
      segmental lordosis was notably more when the cage was placed in lower lumbar
      levels. Additionally, cages placed in the posterior 3rd of the intervertebral
      space had significantly worse segmental lordosis compared to those placed in the
      anterior or middle 3rd. Our study shows that an average delta change of 8.03
      degrees  can be achieved with 12 degrees  cages and this when done at each
      subsequent level results in a progressive harmonious creation of lordosis. IRB
      approval was obtained for this study.

PMID- 28765808
TI  - Altered praxis network underlying limb kinetic apraxia in Parkinson's disease -
      an fMRI study.
AB  - Parkinson's disease (PD) patients frequently suffer from dexterous deficits
      impeding activities of daily living. There is controversy whether impaired fine
      motor skill may stem from limb kinetic apraxia (LKA) rather than bradykinesia.
      Based on classical models of limb praxis LKA is thought to result when premotor
      transmission of time-space information of skilled movements to primary motor
      representations is interrupted. Therefore, using functional magnetic resonance
      imaging (fMRI) we tested the hypothesis that dexterous deficits in PD are
      associated with altered activity and connectivity in left parieto-premotor praxis
      network. Whole-brain analysis of fMRI activity during a task for LKA (coin
      rotation) showed increased activation of superior and inferior parietal lobule
      (SPL, IPL) and ventral premotor cortex (vPM) in PD patients compared to controls.
      For bradykinesia (assessed by finger tapping) a decreased fMRI activity could be
      detected in patients. Additionally, psychophysical interaction analysis showed
      increased functional connectivity between IPL and the posterior hippocampi in
      patients with PD. By contrast, functional connectivity to the right dorsolateral
      prefrontal cortex was decreased in patients with PD compared to controls. In
      conclusion, our data demonstrates that dexterous deficits in PD were associated
      with enhanced fMRI activation of the left praxis network upstream to primary
      motor areas, mirroring a neural correlate for the behavioral dissociation of LKA
      and bradykinesia. Furthermore, the findings suggest that patients recruit
      temporal areas of motor memory as an attempt to compensate for impaired motor
      skills. Finally, dysexecutive function may contribute to the deficit.

PMID- 28765809
TI  - Diffusion tensor imaging in Parkinson's disease: Review and meta-analysis.
AB  - BACKGROUND: Neuroimaging studies help us better understand the pathophysiology
      and symptoms of Parkinson's disease (PD). In several of these studies, diffusion
      tensor imaging (DTI) was used to investigate structural changes in cerebral
      tissue. Although data have been provided as regards to specific brain areas, a
      whole brain meta-analysis is still missing. METHODS: We compiled 39 studies in
      this meta-analysis: 14 used fractional anisotropy (FA), 1 used mean diffusivity
      (MD), and 24 used both indicators. These studies comprised 1855 individuals, 1087
      with PD and 768 healthy controls. Regions of interest were classified
      anatomically (subcortical structures; white matter; cortical areas; cerebellum).
      Our statistical analysis considered the disease effect size (DES) as the main
      variable; the heterogeneity index (I2) and Pearson's correlations between the DES
      and co-variables (demographic, clinical and MRI parameters) were also calculated.
      RESULTS: Our results showed that FA-DES and MD-DES were able to distinguish
      between patients and healthy controls. Significant differences, indicating
      degenerations, were observed within the substantia nigra, the corpus callosum,
      and the cingulate and temporal cortices. Moreover, some findings (particularly in
      the corticospinal tract) suggested opposite brain changes associated with PD. In
      addition, our results demonstrated that MD-DES was particularly sensitive to
      clinical and MRI parameters, such as the number of DTI directions and the echo
      time within white matter. CONCLUSIONS: Despite some limitations, DTI appears as a
      sensitive method to study PD pathophysiology and severity. The association of DTI
      with other MRI methods should also be considered and could benefit the study of
      brain degenerations in PD.

PMID- 28765811
TI  - Molecular identification and characterization of partial COX1 gene from caecal
      worm (Aulonocephalus pennula) in Northern bobwhite (Colinus virginianus) from the
      Rolling Plains Ecoregion of Texas.
AB  - Aulonocephalus pennula is a nematode living in the caeca of the wild Northern
      bobwhite quail (Colinus virginianus) present throughout the Rolling Plains
      Ecoregion of Texas. The cytochrome oxidase 1 (COX 1) gene of the mitochondrial
      genome was used to screen A. pennula in wild quail. Through BLAST analysis,
      similarity of A. pennula to other nematode parasites was compared at the
      nucleotide level. Phylogenetic analysis of A. pennula COX1 indicated
      relationships to Subuluridae, Ascarididae, and Anisakidae. This study on
      molecular characterization of A. pennula provides new insight for the diagnosis
      of caecal worm infections of quail in the Rolling plains Ecoregion of Texas.

PMID- 28765812
TI  - Role of AMPD2 in impaired glucose tolerance induced by high fructose diet.
AB  - A high intake of products containing fructose is known to mediate insulin
      resistance. In the liver, AMPD2, an isoform of AMPD, has important glucose
      metabolic homeostasis functions including maintenance of AMP-activated protein
      kinase (AMPK). We speculated that AMPD2 induces impaired glucose tolerance in
      individuals who consume a high-fructose diet. We gave either a normal-chow (NCD)
      or high-fructose (HFrD) diet for 40 days to 8-week-old male wild-type (WT) and
      Ampd2 -/- homozygote (A2 -/-) C57BL/6 mice. A glucose tolerance test (GTT) and
      pyruvate tolerance test (PTT) were used to evaluate glucose metabolism. In
      addition, gluconeogenesis and glycolysis enzymes, and AMPK phosphorylation in the
      liver were investigated. With consumption of the HFrD, A2 -/- mice showed
      enhanced glucose tolerance in GTT and PTT results as compared to the WT mice,
      which were independent of changes in body weight. Also, the levels of
      phosphoenolpyruvate carboxy kinase and glucose-6-phosphatase (hepatic
      gluconeogenic enzymes) were significantly reduced in A2 -/- as compared to WT
      mice. The hepatic glycolytic enzymes glucokinase, phosphofructokinase, and
      pyruvate kinase were also examined, though there were no significant differences
      between genotypes in regard to both mRNA expression and protein expression under
      HFrD. Surprisingly, hepatic AMPK phosphorylation resulted in no changes in the A2
      -/- as compared to WT mice under these conditions. Our results indicated that
      Ampd2-deficient mice are protected from high fructose diet-induced glycemic
      dysregulation, mainly because of gluconeogenesis inhibition, and indicate a novel
      therapeutic target for type 2 diabetes mellitus.

PMID- 28765813
TI  - Fabricating ordered 2-D nano-structured arrays using nanosphere lithography.
AB  - Recent advances in the use of plasmonic metamaterials to improve absorption of
      light in thin-film solar photovoltaic devices has created a demand for a scalable
      method of patterning large areas with metal nanostructures deposited in an
      ordered array. This article describes two methods of fabricating ordered 2D
      nanosphere colloidal films: spin coating and interface coating. The two methods
      are compared and parameter optimization discussed. The study reveals that: *For
      smaller nanosphere sizes, spin coating is more favorable, while for larger
      nanospheres, the angled interface coating provides more coverage and
      uniformity.*A surfactant-free approach for interface coating is developed to
      fabricate zero-contamination colloidal films.*Each of the methods reaches an
      overall coverage of more than 90% and can be used for nanosphere lithography to
      form plasmonic metamaterials.

PMID- 28765810
TI  - The diversity and impact of hookworm infections in wildlife.
AB  - Hookworms are blood-feeding nematodes that parasitize the alimentary system of
      mammals. Despite their high pathogenic potential, little is known about their
      diversity and impact in wildlife populations. We conducted a systematic review of
      the literature on hookworm infections of wildlife and analyzed 218 studies
      qualitative and quantitatively. At least 68 hookworm species have been described
      in 9 orders, 24 families, and 111 species of wild mammals. Black bears, red
      foxes, and bobcats harbored the highest diversity of hookworm species and
      Ancylostoma pluridentatum, A. tubaeforme, Uncinaria stenocephala and Necator
      americanus were the hookworm species with the highest host diversity index.
      Hookworm infections cause anemia, retarded growth, tissue damage, inflammation
      and significant mortality in several wildlife species. Anemia has been documented
      more commonly in canids, felids and otariids, and retarded growth only in
      otariids. Population- level mortality has been documented through controlled
      studies only in canines and eared seals although sporadic mortality has been
      noticed in felines, bears and elephants. The main driver of hookworm pathogenic
      effects was the hookworm biomass in a population, measured as prevalence, mean
      burden and hookworm size (length). Many studies recorded significant differences
      in prevalence and mean intensity among regions related to contrasts in local
      humidity, temperature, and host population density. These findings, plus the
      ability of hookworms to perpetuate in different host species, create a dynamic
      scenario where changes in climate and the domestic animal-human-wildlife
      interface will potentially affect the dynamics and consequences of hookworm
      infections in wildlife.

PMID- 28765814
TI  - Evaluation of ITS2 for intraspecific identification of Paeonia lactiflora
      cultivars.
AB  - Herbaceous peony (Paeonia lactiflora Pall.) is an important ornamental and
      medicinal plant. DNA barcodes can reveal species identity via the nucleotide
      diversity of short DNA segments. In this study, two main candidate DNA barcodes
      (ITS2 and psbA-trnH) were tested to identify twenty-one cutting cultivars of P.
      lactiflora and their wild species. The efficacy of the candidate DNA barcodes was
      assessed by PCR amplification, sequence quality, sequence diversity, rate of
      correct identification, and phylogenetic analysis. ITS2 was easy to be amplified
      and sequenced among the samples. The identification by Blastn and phylogenetic
      analysis was 95.4% and 63.6%, respectively. For psbA-trnH, the presence of poly A
      T led to sequencing failure which limited its use as DNA barcode candidate.
      Moreover, the authentic efficiency of psbA-trnH was lower than ITS2. The results
      showed that ITS2 is suitable as a candidate DNA barcode for the intraspecific
      identification of P. lactiflora cultivars.

PMID- 28765815
TI  - Aerobiology in Asian airway allergic diseases.

PMID- 28765817
TI  - Allergen-specific intralymphatic immunotherapy in human and animal studies.
AB  - Clinical trials of intralymphatic immunotherapy (ILIT) have been performed to
      overcome the limitations of long-term therapy and the local or systemic
      hypersensitivity reactions in conventional allergen-specific immunotherapy,
      including subcutaneous or sublingual immunotherapy. Additionally, several animal
      studies of ILIT have been conducted in the form of translational or veterinary
      research. We conducted a literature review to examine the treatment efficacy and
      adverse effects of ILIT.

PMID- 28765816
TI  - Classification of chronic rhinosinusitis according to a nasal polyp and tissue
      eosinophilia: limitation of current classification system for Asian population.
AB  - Chronic rhinosinusitis (CRS) can be classified according to the presence of a
      nasal polyp (NP): CRS with NP (CRSwNP) and CRS without NP (CRSsNP). CRSwNP has
      characteristics with high infiltration of tissue eosinophilia with a burst of Th2
      inflammatory cytokine. However recent findings in Eastern Asia countries suggest
      that CRSwNP can be divided according to the presence of tissue eosinophilia.
      Thus, CRSwNP can be classified into eosinophilic and noneosinophilic.
      Eosinophilic CRSwNP seems to have different immunological and clinical feature
      compared to noneosinophilic CRSwNP. From the same point of view, CRSsNP can also
      be divided according to tissue eosinophilia. However, the meaning of this
      dichotomous categorization in CRS seems to be not quite clear. This review focus
      on the limitations in current subclassification of CRS according to the presence
      of NP and tissue eosinophilia and discuss other factors related to tissue
      remodeling and NP generation which may provide clues for the further
      understanding of CRS pathogenesis.

PMID- 28765818
TI  - Characteristics of airborne pollen in Incheon and Seoul (2015-2016).
AB  - BACKGROUND: Pollen allergens are one of the main contributors to the development
      and/or aggravation of allergic rhinitis, allergic conjunctivitis, and asthma.
      OBJECTIVE: An examination of the airborne pollen in residential areas should be
      conducted to aid the diagnosis and treatment of allergic diseases. METHODS:
      Airborne pollen samples were collected from 2 sites in Incheon and 2 in Seoul
      from 2015 to 2016. RESULTS: The highest monthly concentration of airborne pollen
      was observed in May and September each year. Pollen from 32 families and 50
      genera was identified over the 2 years; of these, Pinus spp. showed the highest
      pollen concentration (41.6%), followed by Quercus spp. (25.3%), and Humulus spp.
      (15.3%), the latter of which had the highest concentration among weed pollen. The
      total pollen concentration was significantly higher in Incheon than in Seoul (p =
      0.001 in 2015, p < 0.001 in 2016) and higher in 2016 than in 2015. The
      concentrations of pollen from weed species (Cupressaceae, Humulus spp., Artemisia
      spp., Ambrosia spp., and Chenopodiaceae) and grass species (Gramineae) were
      significantly higher (p < 0.001) than those from tree species. Pollen was
      distributed from February to November. The first pollen identified in both
      regions in each year was Alnus spp. Overall, the total concentration of Quercus
      spp., Betula spp., Humulus spp., Artemisia spp., Ambrosia spp., and
      Chenopodiaceae pollen increased significantly over the 2 years. CONCLUSION:
      Region-specific differences exist in the pollen of major allergenic plants.
      Continuous monitoring of pollen is thus essential for management of pollen
      related allergic disorders in each region.

PMID- 28765819
TI  - A review of 42 asthmatic children with allergic bronchopulmonary aspergillosis.
AB  - BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) in children with
      asthma, not associated with cystic fibrosis, is yet to receive the recognition it
      deserves. OBJECTIVE: To highlight the presentation of ABPA in children with
      asthma. METHODS: This retrospective review documents the occurrence of pediatric
      ABPA over a period of 31 years in one unit. Children with asthma, eosinophilia
      and infiltrates on chest radiograph were screened for ABPA. In these patients,
      demonstration of immediate hypersensitivity response against Aspergillus species
      along with serological profile and pulmonary function testing were done.
      Bronchography/computed tomography (CT) of the chest demonstrated central
      bronchiectasis (CB). CT of the paranasal sinuses was done in patients with upper
      airways symptoms. In those suspected with allergic Aspergillus sinusitis (AAS)
      consent was sought from the parents for the invasive procedure needed for the
      diagnosis of AAS. RESULTS: Of the 349 patients with ABPA diagnosed, 42 (12.03%)
      were in the pediatric age group. The mean age on presentation was 12.9 +/- 4
      years with a male preponderance. All patients had asthma and positive
      intradermal/skin prick test against Aspergillus species. Ring shadows, the most
      common radiological presentation, were seen in 28 of 42 patients.
      Bronchography/CT of the chest demonstrated CB, a feature pathognomic of ABPA, in
      32 of 42 patients. High attenuation mucus plugs was observed in 7 of 36 patients
      while ABPA-seropositive was diagnosed in 10 of 42 patients. On imaging, sinusitis
      was seen in 20 of 30 patients with upper airways symptoms of whom eight had
      suspected AAS. Three parents consented for surgery, which confirmed the
      diagnosis. CONCLUSION: This study highlights the need to evaluate asthmatic
      children for ABPA as also to exclude AAS.

PMID- 28765820
TI  - Self-report prevalence and associated factors to drug hypersensitivity in Mexican
      young adults.
AB  - BACKGROUND: Drug hypersensitivity is defined as any unfavorable reaction that
      occurs after the administration of any drug. It may or may not be mediated by the
      involvement of the immune system. Epidemiological data related to drug
      hypersensitivity reactions in our country are scarce. OBJECTIVE: To determine the
      prevalence of drug hypersensitivity in a group of young adults, as well as to
      identify associated factors. METHODS: A structured questionnaire was applied to
      young people aged 18 to 25 years. The instrument was oriented to identify
      reactions of drug hypersensitivity, as well as the most prevalent drugs involved.
      In addition, a personal and family history of atopic diseases was included.
      Analysis for associations between variables was been done through logistic
      regression. RESULTS: The prevalence of drug hypersensitivity reactions was 12%
      (144 of 1,200). The antibiotics were the agents most related to hypersensitivity
      reactions (9.8%) followed by nonsteroidal anti-inflammatory drugs (1.6%). Factors
      associated with drug hypersensitivity were a personal history of asthma, odds
      ratio (OR) 3.15 (95% confidence interval [CI], 1.44-6.91), maternal and paternal
      history of drug hypersensitivity, OR 2.33 (95% CI, 1.21-4.48) and OR 3.11 (95%
      CI, 1.22-7.92), respectively. CONCLUSION: The results of this research show that
      drug hypersensitivity in young adults is a highly prevalent event and it is
      associated with personal history of asthma and history of drug hypersensitivity
      in parents.

PMID- 28765821
TI  - Increased antioxidant activity after exposure of ozone in murine asthma model.
AB  - BACKGROUND: Ozone is well known as an important component of ambient air
      pollutants. Ozone can aggravate respiratory symptoms in patients with bronchial
      asthma, but, not in healthy person. We hypothesized asthma itself may show
      different response to ozone compared to nonasthma. OBJECTIVE: This study was
      performed to evaluate the differences of response to ozone between normal and
      asthmatic mice model in terms of status of oxidant injury and antioxidant
      activity. METHODS: Three parts per million of ozone was exposed to ovalbumin
      (OVA)-induced murine asthma model for 3 hours at 3, 7, 14, 21 days after
      completion of asthma model. Airway responsiveness to methacholine was measured
      after completion of asthma model. Bronchoalveolar lavage (BAL), protein
      extraction from lung for Western blot and immunohistochemistry of 4-hydroxy-2
      nonenal (4-HNE), proliferating cell nuclear antigen (PCNA), NF-E2 related factor
      2 (Nrf-2), and activity of glutathione were performed at before and each ozone
      exposure day. RESULTS: Airway hyper-responsiveness and increased eosinophils in
      BAL fluid were observed in asthma model. In asthma model, the expression of 4-HNE
      already more increased at baseline (without ozone) compared to those in sham
      model. This increased expression is more enhanced at 3 days after ozone exposure.
      The expression of PCNA was significantly increased in OVA-model compared to those
      in sham model. The expression of Nrf-2 was observed at baseline, and 3 and 7 days
      after exposure ozone in asthma model, but not in sham model. The activity of
      glutathione increased significantly after exposure of ozone, but not in sham
      model. CONCLUSION: Murine asthma model has enhanced oxygen toxicity and
      antioxidant activity response to ozone.

PMID- 28765822
TI  - Is Euxyl K400 patch testing useful in the general population?

PMID- 28765823
TI  - Past, present, and future of pharmacovigilance in Korea.
AB  - As an essential part of patient safety, pharmacovigilance is of worldwide
      interest and should expand its scope and focus on new emerging issues. South
      Korea has been making continuous efforts in the field of pharmacovigilance for
      the last 3 decades since voluntary adverse drug reaction (ADR) reporting system
      was first launched in 1988. Korea joined the World Health Organization Program
      for International Drug Monitoring in 1992, and the activities of
      Pharmacovigilance Research Network, Korean Society for Pharmacoepidemiology and
      Risk Management, and Regional Pharmacovigilance Center (RPVC) have contributed to
      the remarkable progress in the pharmacovigilance area and global status. RPVCs
      have played pivotal roles in establishment of pharmacovigilance system in Korea
      by monitoring voluntary ADR reports. RPVCs started with 3 hospitals in 2006 and
      have now expanded to 27 hospitals nationwide. The Korea Institute of Drug Safety
      & Risk Management was established in 2012 and in charge of operating the
      decentralized national pharmacovigilance system. The voluntary report of ADR,
      which is the basis of current pharmacovigilance system, has various limitations
      and an active surveillance system can be the overarching alternative. This change
      in pharmacovigilance paradigm is a global trend and Korea has excellent
      infrastructure such as broad distribution of electronic medical recording systems
      and a nationwide single healthcare insurance. As a result, the pharmacovigilance
      in Korea is now expected to progress to a new active surveillance system from
      traditional spontaneous reporting system.

PMID- 28765824
TI  - Is nonhomogeneous expression of tissue mast cells or allergen specific IgEs bound
      to tissue mast cells possible?
AB  - Skin prick tests (SPTs) are widely used to demonstrate an IgE-mediated
      hypersensitivity reaction to a specific allergen. However, local allergic
      conditions cannot be diagnosed with SPTs. Local specific IgE production was only
      presented before in mucosal tissues. We present a patient with house dust mite
      sensitization that had variable SPTs results in different body regions.

PMID- 28765825
TI  - Comparison of the Effect of PRP, PRF and Induced Bleeding in the
      Revascularization of Teeth with Necrotic Pulp and Open Apex: A Triple Blind
      Randomized Clinical Trial.
AB  - INTRODUCTION: Treatment of a tooth with necrotic pulp and open apex is a special
      challenge to the clinicians. Apexification with calcium hydroxide and MTA barrier
      technique fails to induce continued root maturation which makes the tooth
      susceptible to root fracture. Hence, an ideal outcome for such a tooth should be
      regeneration of pulp like tissue into the root canal capable of continuing normal
      root maturation. AIM: This study aims to compare the effect of Platelet Rich
      Fibrin (PRF), induced bleeding technique and Platelet Rich Plasma (PRP) in the
      revascularization of tooth with necrotic pulp and open apex. The main objectives
      of the study were to: (a) Radiographically evaluate the continuation of root
      development, increase in the dentin wall thickness and narrowing of canal space,
      apical closure and resolution of the periapical lesion; and to (b) To clinically
      evaluate the response to pulp sensibility testing and response to percussion and
      palpation tests. MATERIALS AND METHODS: Sixty patients (6 to 28 years) with
      necrotic immature permanent tooth were randomly categorised into three groups
      after the root canal disinfection procedure. PRF as scaffolding material (Group
      A: n=20), revascularization with conventional induced bleeding technique (Group
      B: n=20), and PRP as the biomaterial (Group C: n=20). The primary outcome
      variable was measured using Periapical Index (PAI) (for periapical healing), Chen
      and Chen index (for apical responses), Schei's ruler (for root lengthening and
      root thickening) and other clinical parameters. The Chi-square test was used to
      interpret the data among the three groups at the end of 12 months for the
      variables root lengthening and lateral wall thickness. ANOVA test was performed
      to compare the mean of the PAI scores of the three groups at preoperative stage
      and 12 months. If statistically significant, Bonferroni test was done to compare
      the outcome among the three groups. The significant level was set at p<0.05.
      Kappa agreement was used to see whether the clinical criteria of success
      (asymptomatic) were in agreement with radiographic criteria. RESULTS: At the end
      of 12 months, patients presented with no pain and no signs of reinfection or no
      radiographic enlargement of the pre-existing apical pathosis in all the three
      groups. PRP was better than PRF and induced bleeding technique with respect to
      periapical wound healing when used in the regenerative endodontic procedures. The
      groups were comparable on grounds of root lengthening and lateral wall
      thickening. Type 3 apical response was the most common apical response in all the
      three groups. CONCLUSION: On analysing the pros and cons of the techniques
      performed, it is wise to establish induced bleeding technique as the standard
      endodontic procedure for revascularization of a non vital immature permanent
      tooth.

PMID- 28765826
TI  - Validity and reliability of grade scoring in the diagnosis of exercise-induced
      laryngeal obstruction.
AB  - The current gold-standard method for diagnosing exercise-induced laryngeal
      obstruction (EILO) is continuous laryngoscopy during exercise (CLE), with
      severity classified by a visual grade scoring system. We evaluated the precision
      of this approach, by evaluating test-retest reliability of CLE and both inter-
      and intra-rater variability. In this prospective case-control study, subjects
      completed four consecutive treadmill CLE tests under identical conditions.
      Laryngoscopic video recordings were anonymised and graded by three expert raters.
      2 months following initial scoring, videos were re-randomised and rating repeated
      to assess intra-rater agreement. 20 subjects (16 cases and four controls)
      completed four CLE tests. The time to exhaustion increased by 30 s (95% CI 0.02
      57.8, p<0.05) in the second CLE compared with the first test, but remained
      identical in the subsequent tests. Only one-third of subjects retained their
      initial diagnosis in the subsequent three tests. Inter-rater agreement on grade
      scores (weighted Cohen's kappa) was 0.16-0.45, while intra-rater agreement ranged
      from 0.30 to 0.67. The CLE test is key in the diagnostic assessment of patients
      with EILO. However, the widely adopted visual grade scoring system does not
      appear to be a robust means for reliably classifying severity of EILO.

PMID- 28765828
TI  - Data on gender contrasts in the risk of incident myocardial infarction by age.
      The Tromso Study 1979-2012.
AB  - The data presented in this article relate to the research article entitled "Risk
      of incident myocardial infarction by gender: Interactions with serum lipids,
      blood pressure and smoking. The Tromso Study 1979-2012" (Albrektsen et al., 2017)
      [1]. Data quantify the gender differences in the risk of myocardial infarction
      (MI) in terms of incidence rate ratios (IRR), in subgroups defined by serum
      lipids, blood pressure and smoking among persons aged 35-54 years, 55-74 years
      and 75-94 years, respectively. Data also describe the age- and gender-specific
      linear associations with the coronary heart disease (CHD) risk factors. IRRs for
      combined categories of age, gender and a CHD risk factor, with each category
      compared to the same reference group, are also shown. IRRs were calculated as
      estimates of relative risk in Poisson regression analyses of person-years at
      risk. Among 33,859 individuals at risk, a total of 622, 1308 and 816 were
      diagnosed with MI at ages 35-54, 55-74 and 75-94 years, respectively.

PMID- 28765827
TI  - Traceless Targeting and Isolation of Gene-Edited Immortalized Keratinocytes from
      Epidermolysis Bullosa Simplex Patients.
AB  - Epidermolysis bullosa simplex (EBS) is a blistering skin disease caused by
      dominant-negative mutations in either KRT5 or KRT14, resulting in impairment of
      keratin filament structure and epidermal fragility. Currently, nearly 200
      mutations distributed across the entire length of these genes are known to cause
      EBS. Genome editing using programmable nucleases enables the development of ex
      vivo gene therapies for dominant-negative genetic diseases. A clinically feasible
      strategy involves the disruption of the mutant allele while leaving the wild-type
      allele unaffected. Our aim was to develop a traceless approach to efficiently
      disrupt KRT5 alleles using TALENs displaying unbiased monoallelic disruption
      events and devise a strategy that allows for subsequent screening and isolation
      of correctly modified keratinocyte clones without the need for selection markers.
      Here we report on TALENs that efficiently disrupt the KRT5 locus in immortalized
      patient-derived EBS keratinocytes. Inactivation of the mutant allele using a
      TALEN working at sub-optimal levels resulted in restoration of intermediate
      filament architecture. This approach can be used for the functional inactivation
      of any mutant keratin allele regardless of the position of the mutation within
      the gene and is furthermore applicable to the treatment of other inherited skin
      disorders.

PMID- 28765829
TI  - Transcriptome of melanoma cells from two mouse models, Tyr:NRasQ61K and Tyr:Rack1
      HA, Tyr:NRasQ61K.
AB  - The transcriptome sequencing of melanoma cells from two mouse models differing in
      the expression level of the scaffold protein Receptor for activated C kinase
      (RACK1) are presented. Primary melanoma cells were harvested from Tyr:NRasQ61K;
      Pax3GFP/+ mice, with or without the Tyr:Rack1-HA transgene. Cells were cultured
      and infected with scramble shRNA or Rack1-targeting shRNA, on technical
      triplicates of viral infection. Libraries were prepared by selecting
      polyadenylated mRNAs and RNA Sequencing (RNASeq) was performed. Samples are
      described in the SRA portal (SRP096162) and FASTQ files have been deposited in
      Sequence Read Archive (accession numbers: SRR5150106 to SRR5150117). The
      interpretation of these data is presented in the following research article:
      "RACK1 cooperates with NRASQ61K to promote melanoma in vivo" (Campagne et al.,
      2017, doi: 10.1016/j.cellsig.2017.03.015) [1].

PMID- 28765830
TI  - Quality control and biophysical characterisation data of VanSA.
AB  - This data article presents the results from quality control experiments including
      N-terminal sequencing, SEC-MALS and Mass Spectrometry for purified VanSA used in
      experiments described in (Hughes et al., 2017) [1]; in addition to ligand
      interaction measurements and thermal melting curves of VanSA in the presence of
      screened ligands from circular dichroism measurements as well as UV-vis
      absorbance spectra for the binding interaction of VanSA in the presence of
      screened ligands.

PMID- 28765831
TI  - The dataset describes: HIF-1 alpha expression and LPS mediated cytokine
      production in MKP-1 deficient bone marrow derived murine macrophages.
AB  - The data presented in this article are related to the research article entitled
      "MKP-1 negatively regulates LPS-mediated IL-1beta production through p38
      activation and HIF-1alpha expression" (Talwar et al., 2017) [1]. This data
      describes that LPS-mediated p38 and JNK phosphorylation is enhanced in MKP-1
      deficient macrophages. HIF-1alpha expression and its nuclear accumulation are
      significantly increased in the nuclear extracts of MKP-1 deficient BMDMs. MKP-1
      deficient BMDMs exhibited higher expression of the coactivator p300 of HIF-1alpha
      both at baseline and after LPS challenge. Inhibition of p38 MAP kinase decreased
      LPS mediated HIF-1alpha protein levels and its nuclear translocation in MKP-1
      deficient BMDMs. Inhibition of p38 MAP kinase inhibited LPS induced pro
      inflammatory cytokines including IL-1beta, IL-6 and TNF-alpha.

PMID- 28765832
TI  - Electrical circuit model of ITO/AZO/Ge photodetector.
AB  - In this data article, ITO/AZO/Ge photodetector was investigated for electrical
      circuit model. Due to the double (ITO and AZO) transparent metal-oxide films
      (DOI:10.1016/j.mssp.2016.03.007) (Yun et al., 2016) [1], the Ge heterojunction
      device has a better interface quality due to the AZO layer with a low electrical
      resistance due to the ITO layer (Yun et al., 2015) [2]. The electrical and
      interfacial benefitted ITO/AZO/Ge heterojunction shows the quality Schottky
      junction. In order to investigate the device, the ITO/AZO/Ge heterojunction was
      analyzed by R-C circuit model using the impedance spectroscopy.

PMID- 28765833
TI  - Sample preparation and electrochemical data of Co3O4 working electrode for
      seawater splitting.
AB  - In this data article, we presented the electrochemical data of the working
      electrode made of Co3O4 semi-transparent film. Electrochemically stable, porous
      nature of Kirkendall-diffusion grown Co3O4 films were applied to generate
      hydrogen from the seawater splitting (Patel et al., 2017) [1]. The data presented
      in this article includes the photograph of prepared samples, polarization curves
      for water oxidation and Tafel plot, linear sweep voltammetry measurements under
      the pulsed light condition in 0.1 M Na2S2O3 electrolyte, and transient
      photoresponses with natural sea water. Moreover, seawater splitting using the
      Co3O4 working electrode is demonstrated.

PMID- 28765834
TI  - Proteogenomics data for deciphering Frankia coriariae interactions with root
      exudates from three host plants.
AB  - Frankia coriariae BMG5.1 cells were incubated with root exudates derived from
      compatible (Coriaria myrtifolia), incompatible (Alnus glutinosa) and non
      actinorhizal (Cucumis melo) host plants. Bacteria cells and their exoproteomes
      were analyzed by high-throughput proteomics using a Q-Exactive HF high resolution
      tandem mass spectrometer incorporating an ultra-high-field orbitrap analyzer.
      MS/MS spectra were assigned with two protein sequence databases derived from the
      closely-related genomes from strains BMG5.1 andDg1, the Frankia symbiont of
      Datisca glomerata. The tandem mass spectrometry data accompanying the manuscript
      describing the database searches and comparative analysis (Ktari et al., 2017,
      doi.org/10.3389/fmicb.2017.00720) [1] have been deposited to the ProteomeXchange
      with identifiers PXD005979 (whole cell proteomes) and PXD005980 (exoproteome
      data).

PMID- 28765835
TI  - Cognitive behavioral therapy for insomnia in Parkinson's disease: a case series.
AB  - Chronic insomnia is common in patients with Parkinson's disease. There are
      limited data to guide its treatment in this patient population, especially in
      regards to non-pharmacologic interventions, some of which are highly effective in
      the non-Parkinson's disease population. The aim of this study is to describe a
      series of Parkinson's disease patients who underwent cognitive behavioral therapy
      for insomnia (CBTi). Parkinson's disease patients who had undergone a baseline
      and at least one follow-up CBTi session were identified. Electronic medical
      records and pre-treatment and post-treatment patient sleep diaries were reviewed.
      Sleep measures of interest included wake time after sleep onset, sleep
      efficiency, sleep onset latency, and total sleep time. Pre-treatment and post
      treatment values were compared within subjects using paired t-test. Five patients
      were included. Patients attended an average of eight sessions of CBTi (range 5
      12). Significant increases in sleep efficiency (p = 0.02) and decreases in number
      of awakenings per night (p = 0.02) were found. Our data provide preliminary
      evidence that cognitive behavioral therapy is an effective treatment for insomnia
      in Parkinson's disease, and is well tolerated and well received by patients.
      Given the limited data supporting use of medications to treat chronic insomnia in
      Parkinson's disease, combined with their risks, randomized trials to demonstrate
      the efficacy of CBTi in Parkinson's disease are warranted.

PMID- 28765837
TI  - The impact of finasteride and dutasteride treatments on proliferation, apoptosis,
      androgen receptor, 5alpha-reductase 1 and 5alpha-reductase 2 in TRAMP mouse
      prostates.
AB  - BACKGROUND: Previously, we studied the effect of finasteride- or dutasteride
      containing diets in male C57BL/6 TRAMP x FVB mice. Pre (6 weeks of age) and post
      (12 weeks of age) groups received finasteride or dutasteride to determine the
      efficacy of these pharmaceuticals on prostate cancer (PCa) development in male
      C57BL/6 TRAMP x FVB mice. Post-Dutasteride treatment was more effective than Pre
      Dutasteride treatment, and dutasteride treatments were more effective than
      finasteride treatments in decreasing prostatic intraepithelial neoplasia (PIN)
      progression and PCa development. Finasteride and Pre-Dutasteride treatments
      significantly decreased high-grade PIN incidence, but increased poorly
      differentiated PCa incidence. In this study, molecular changes in prostates of
      these mice were characterized in an effort to elucidate the discordant response
      in Pre-Dutasteride and finasteride groups, and determine why Post-Dutasteride
      treatment was more effective. METHOD/PRINCIPAL FINDINGS: Ki-67 (proliferation
      marker) and androgen receptor (AR) protein, apoptotic DNA fragmentation (TUNEL
      assay), 5alpha-reductase 1 (5alphaR1) and 5alpha-reductase 2 (5alphaR2) mRNA were
      quantified in male TRAMP mice prostate tissues with genitourinary weight < 1 and
      > 1 gram. Overall, proliferation and AR were decreased and apoptosis was
      increased in most tumors versus prostate epithelium and hyperplasia.
      Proliferation and AR were increased notably in hyperplasia versus prostate
      epithelium and tumor. There were no clear trends or differences in 5alpha
      reductase 1 and 5alpha-reductase 2 levels between large and small tumors. The
      discordant response in Pre-Finasteride and Pre-Dutasteride groups may be due to
      upregulated 5alphaR1 levels in large versus small tumors. It is not clear what
      the mechanism is for the different response in the Post-Finasteride group. Post
      Dutasteride treatment was more effective than Pre-Dutasteride treatment in
      decreasing 5alphaR1 in large tumors. Therefore, this may be why this treatment
      was more effective in decreasing PIN progression and PCa development. CONCLUSION:
      The effect of finasteride and dutasteride on these biomarkers did not clearly
      elucidate their mechanism of action, but tumor 5alphaR1 levels were significantly
      positively correlated with adjusted prostate severe lesion score.

PMID- 28765836
TI  - Muscle Stem Cell and Physical Activity: What Point is the Debate at?
AB  - In the last 15 years, it emerged that the practice of regular physical activity
      reduces the risks of many diseases (cardiovascular diseases, diabetes, etc.) and
      it is fundamental in weight control and energy consuming to contrast obesity.
      Different groups proposed many molecular mechanisms as responsible for the
      positive effects of physical activity in healthy life. However, many points
      remain to be clarified. In this mini-review we reported the latest observations
      on the effects of physical exercise on healthy skeletal and cardiac muscle
      focusing on muscle stem cells. The last ones represent the fundamental elements
      for muscle regeneration post injury, but also for healthy muscle homeostasis.
      Interestingly, in both muscle tissues the morphological consequence of physical
      activity is a physiological hypertrophy that depends on different phenomena both
      in differentiated cells and stem cells. The signaling pathways for physical
      exercise effects present common elements in skeletal and cardiac muscle, like
      activation of specific transcription factors, proliferative pathways, and
      cytokines. More recently, post translational (miRNAs) or epigenetic (DNA
      methylation) modifications have been demonstrated. However, several points remain
      unresolved thus requiring new research on the effect of exercise on muscle stem
      cells.

PMID- 28765839
TI  - Recent developments in sensing methods for eutrophying nutrients with a focus on
      automation for environmental applications.
AB  - The demand for autonomous sensors for unattended, continuous nutrient monitoring
      in water is rapidly growing with the increasing need for more frequent and
      widespread environmental pollution monitoring. Legislative bodies, local
      authorities and industries all require frequent water quality monitoring,
      however, this is time and labour intensive, and an expensive undertaking.
      Autonomous sensors allow for frequent, unattended data collection. While this
      solves the time and labour intensive aspects of water monitoring, sensors can be
      very expensive. Development of low-cost sensors is essential to realise the
      concept of Internet of Things (IoT). However there is much work yet to be done in
      this field. This article reviews current literature on the research and
      development efforts towards deployable autonomous sensors for phosphorus (in the
      form of phosphate) and nitrogen (in the form of nitrate), with a focus on
      analytical performance and cost considerations. Additionally, some recent sensing
      approaches that could be automated in the future are included, along with an
      overview of approaches to monitoring both nutrients. These approaches are
      compared with standard laboratory methods and also with commercially available
      sensors for both phosphate and nitrate. Application of nutrient sensors in
      agriculture is discussed as an example of how sensor networks can provide
      improvements in decision making.

PMID- 28765838
TI  - Sex specific molecular responses of quick-to-court protein in Indian malarial
      vector Anopheles culicifacies: conflict of mating versus blood feeding behaviour.
AB  - Understanding the molecular basis of mosquito behavioural complexity plays a
      central role in designing novel molecular tools to fight against their vector
      borne diseases. Although the olfactory system plays an important role in guiding
      and managing many behavioural responses including feeding and mating, but the sex
      specific regulation of olfactory responses remain poorly investigated. From our
      ongoing transcriptomic data annotation of olfactory tissue of blood fed adult
      female An. culicifacies mosquitoes; we have identified a 383 bp long unique
      transcript encoding a Drosophila homolog of the quick-to-court protein.
      Previously this was shown to regulate courtship behaviour in adult male
      Drosophila. A comprehensive in silico analysis of the quick-to-court (qtc) gene
      of An. culicifacies (Ac-qtc) predicts a 1536 bp single copy gene encoding 511
      amino acid protein, having a high degree of conservation with other insect
      homologs. The age-dependent increased expression of putative Ac-qtc correlated
      with the maturation of the olfactory system, necessary to meet the sex-specific
      conflicting demand of mating (mate finding) versus host-seeking behavioural
      responses. Sixteen to eighteen hours of starvation did not alter Ac-qtc
      expression in both sexes, however, blood feeding significantly modulated its
      response in the adult female mosquitoes, confirming that it may not be involved
      in sugar feeding associated behavioural regulation. Finally, a dual behavioural
      and molecular assay indicated that natural dysregulation of Ac-qtc in the late
      evening might promote the mating events for successful insemination. We
      hypothesize that Ac-qtc may play a unique role to regulate the sex-specific
      conflicting demand of mosquito courtship behaviour versus blood feeding behaviour
      in the adult female mosquitoes. Further elucidation of this molecular mechanism
      may provide further information to evaluate Ac-qtc as a key molecular target for
      mosquito-borne disease management.

PMID- 28765840
TI  - Fluorescence-switching RNA for detection of bacterial ribosomes.
AB  - We have developed an efficient chemical system that allows quantification of
      bacterial ribosomes by fluorescence-based analysis. The key component in the
      system is the exciton-controlled fluorescent RNA aptamer, which recognizes
      neomycin B. The intensity of fluorescence from such a ribosome-sensing system
      increased drastically in the presence of Escherichia coli.

PMID- 28765842
TI  - Detection of a cancer biomarker protein on modified cellulose paper by
      fluorescence using aptamer-linked quantum dots.
AB  - The development of point-of-care bioassays for sensitive screening of protein
      based cancer biomarkers would improve the opportunity for early stage diagnosis.
      A strategy for a fluorescence resonance energy transfer (FRET)-based bioassay has
      been investigated that makes use of modified cellulose paper for the detection of
      an epithelial cell adhesion molecule (EpCAM), which is a transmembrane
      glycoprotein that is overexpressed in several tumors of epithelial origin. The
      paper matrix was a substrate for immobilized aptamer-linked quantum dots (QDs
      Apt) and Cy3 labeled complementary DNA (cDNA), which served as a donor and an
      acceptor, respectively. Competitive binding of EpCAM displaced the cDNA,
      resulting in the reduction of FRET. The paper-based bioassay was able to detect
      EpCAM in buffer solution as well as in 10% bovine serum solution using a reaction
      time of no more than 60 minutes. The dynamic range was 1-100 nM in buffer with a
      precision better than 4%, and the limit of detection was 250 pM in buffer and 600
      pM in 10% serum.

PMID- 28765841
TI  - Capture, amplification, and global profiling of microRNAs from low quantities of
      whole cell lysate.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression at the
      post-transcriptional level via a complex regulatory network that requires genome
      wide miRNA profiling to dissect. The patterns of miRNA expression at the genome
      scale are rich in diagnostic and prognostic information for human diseases such
      as cancers. This analysis, however, requires multi-step purification of RNAs from
      large quantities of cells, which is not only time consuming and costly but also
      challenging in situations where cell numbers are limited. In this study, we
      report direct capture, amplification, and library preparation of miRNAs from
      whole cell lysate without the need of pre-purification. As a result, it enables
      genome-wide miRNA profiling reproducibly with low quantity of cell samples (~500
      hematopoietic cells). Specifically, we conducted a systematic investigation of
      two key steps - cell lysis for miRNA release and 3' adaptor ligation required for
      direct miRNA capture and amplification. The obtained expression profile not only
      distinguishes cell types but also detects individual miRNA alterations in closely
      related isogenic cell lines. This approach, which is substantially simple as
      compared to the standard methods because of elimination of the need for RNA
      purification, is advantageous for the measurement of low quantity samples.

PMID- 28765843
TI  - Alkali and alkaline earth metal ion binding by a foldamer capsule: selective
      recognition of magnesium hydrate.
AB  - Alkali and alkaline earth metal ion binding by an aromatic oligoamide foldamer
      was shown to induce its folding into a helical capsule. CD and NMR titrations
      revealed tight and selective binding of Mg2+. Crystallographic studies
      demonstrated that, depending on the metal, binding may involve the first or
      second coordination spheres of the metal hydrates.

PMID- 28765844
TI  - A new gallium complex inhibits tumor cell invasion and matrix metalloproteinase
      MMP-14 expression and activity.
AB  - In this study, we investigated the effect of [N-(5-chloro-2-hydroxyphenyl)-l
      aspartato] chlorogallate (GS2), a new water soluble gallium complex, on cell
      invasion and on the expression and activity of matrix metalloproteinases (MMPs)
      in human metastatic HT-1080 fibrosarcoma and MDA-MB 231 breast carcinoma cells.
      The effect on cell invasion was studied using a modified Boyden chamber coated
      with a type-I collagen. We analyzed the effect of GS2 on MMP-2, MMP-9, and MMP-14
      via zymography and enzymatic assay using high affinity fluorogenic substrates.
      The expression of MMP mRNA was analyzed via qRT-PCR. GS2 induced a decrease in
      cell invasion. A dose-dependent inhibition effect was observed on the activities
      of MMP-2, MMP-9, and MMP-14 with the IC50 values of 168, 82, and 20 MUM,
      respectively. A decrease in the expression of MMP-14 mRNA was observed in both
      cell lines, whereas the expression of MMP-2 and MMP-9 mRNA was decreased only in
      the MDA-MB231 cells. Data obtained for the expression of MMP-14 mRNA were
      confirmed via Western blotting. In fact, MMP-14 expression was decreased in the
      presence of GS2. Overall, these data show that GS2 is a promising compound for
      anti-invasive and anticancer therapy.

PMID- 28765845
TI  - Spatially offset Raman spectroscopy for photon migration studies in bones with
      different mineralization levels.
AB  - The ability of Spatially Offset Raman Spectroscopy (SORS) to obtain chemically
      specific information from below the sample surface makes it a promising technique
      for non-invasive in vivo diagnosis of bone conditions by sampling bone through
      the skin. The depth below a surface interrogated by SORS depends on the system's
      optical properties and is difficult to estimate for complex bone material. This
      paper uses 830 nm laser excitation to investigate the influence of bone
      mineralization on photon migration properties in deer antler cortex, equine
      metacarpal cortex and whale tympanic bulla. Thin slices form each type of bone
      (thickness: 0.6-1.0 mm) were cut and put together on top of each other forming
      stacks with a total thickness of 4.1-4.7 mm. A 0.38 mm thin slice of
      polytetrafluoroethylene (PTFE) served as a test material for Raman signal
      recovery and was placed in between the individual bone slices within the stack.
      At SORS offsets of 8.0-9.5 mm Raman bands of materials not present in healthy
      bone (e.g. PTFE as an example) can be recovered through 4.4-4.7 mm of cortical
      bone tissue, depending on mineralization level and porosity. These findings
      significantly increase our understanding of SORS analysis through bones of
      different composition and provide information that is vital to determine the
      value of SORS as a medical diagnostic technique. The data serve to define which
      SORS offset is best deployed for the non-invasive detection of chemically
      specific markers associated with infection, degeneration and disease or cancer
      within bone.

PMID- 28765846
TI  - Enhanced enzymatic activity from phosphotriesterase trimer gold nanoparticle
      bioconjugates for pesticide detection.
AB  - The rapid detection of organophosphates (OPs), a class of strong neurotoxins, is
      critically important for monitoring acute insecticide exposure and potential
      chemical warfare agent use. Herein, we improve the enzymatic activity of a
      phosphotriesterase trimer (PTE3), an enzyme that selectively recognizes OPs
      directly, by conjugation with distinctly sized (i.e., 5, 10, and 20 nm diameter)
      gold nanoparticles (AuNPs). The number of enzymes immobilized on the AuNP was
      controlled by conjugating increasing molar ratios of PTE3 onto the AuNP surface
      via metal affinity coordination. This occurs between the PTE3-His6 termini and
      the AuNP-displayed Ni2+-nitrilotriacetic acid end groups and was confirmed with
      gel electrophoresis. The enzymatic efficiency of the resultant PTE3-AuNP
      bioconjugates was analyzed via enzyme progress curves acquired from two distinct
      assay formats that compared free unbound PTE3 with the following PTE3-AuNP
      bioconjugates: (1) fixed concentration of AuNPs while increasing the bioconjugate
      molar ratio of PTE3 displayed around the AuNP and (2) fixed concentration of PTE3
      while increasing the bioconjugate molar ratio of PTE3-AuNP by decreasing the AuNP
      concentration. Both assay formats monitored the absorbance of p-nitrophenol that
      was produced as PTE3 hydrolyzed the substrate paraoxon, a commercial insecticide
      and OP nerve agent simulant. Results demonstrate a general equivalent trend
      between the two formats. For all experiments, a maximum enzymatic velocity (Vmax)
      increased by 17-fold over free enzyme for the lowest PTE3-AuNP ratio and the
      largest AuNP (i.e., ratio of 1 : 1, 20 nm dia. AuNP). This work provides a route
      to improve enzymatic OP detection strategies with enzyme-NP bioconjugates.

PMID- 28765847
TI  - Highly efficient enrichment of N-linked glycopeptides using a hydrophilic
      covalent-organic framework.
AB  - The enrichment of glycopeptides plays an important role in glycoproteomics. In
      this paper, a covalent-organic framework called TpPa-1, synthesized by the Schiff
      base reaction of 1,3,5-triformylphloroglucinol and paraphenylenediamine, was
      first successfully utilized as a hydrophilic porous material for N-linked
      glycopeptide enrichment. Using this material, interference from non-glycopeptides
      could be efficiently eliminated, which facilitated the mass spectrometry
      detection of glycopeptides. By capturing N-linked glycopeptides from tryptic
      digests of human IgG, our method was proved to have high sensitivity at the
      femtomole level. And it showed superior selectivity for glycopeptides even when
      non-glycopeptides were 1000 times more concentrated. Due to the strong covalent
      bonds, this material possessed good stability and could be repeatedly used for at
      least 10 times. The ultra-low mass density and abundant binding sites also
      provided it with high binding capacity (178 mg g-1, IgG/TpPa-1). Moreover, N
      linked glycopeptides were easily enriched by this material from only 10 MUL human
      serum, which demonstrated its potential in pretreatment of complex biological
      samples.

PMID- 28765848
TI  - Surface-assisted dehydrogenative homocoupling and cyclodehydrogenation of mesityl
      groups on a copper surface.
AB  - We present for the first time an adjacent dehydrogenative homocoupling and
      cyclodehydrogenation reaction of mesityl groups to form a synthetic nanoribbon on
      Cu(110). Submolecular resolution scanning tunneling microscopy (STM) observations
      and density functional theory (DFT) calculations confirm the formation of an
      ethylene (-CH[double bond, length as m-dash]CH-) unit or an aromatic six-membered
      ring group.

PMID- 28765849
TI  - Peptide binding to metal oxide nanoparticles.
AB  - Magnetic metal oxide nanoparticles demonstrate great applicability in several
      fields such as biotechnology, medicine and catalysis. A stable, magnetic and low
      cost material, nanoscale magnetite, is an interesting adsorbent for protein
      purification. Downstream processing can account for up to 80% of the total
      production costs in biotechnological production. As such, the development of new
      innovative separation methods can be regarded as highly profitable. While short
      peptide sequences can be used as specific affinity tags for functionalised
      adsorber surfaces, they need expensive affinity ligands on the particle surface
      for adsorption. In order to identify peptide tags for several non-functionalised
      inorganic surfaces, different binding conditions to iron oxide nanoparticles are
      evaluated. Therefore, magnetite nanoparticles in a range of 5-20 nm were
      synthesised with a co-precipitation method. Zeta potential measurements indicated
      an amphiphilic surface with an isoelectric point in the neutral pH region.
      Glutamic acid-based homo-peptides were used as affinity peptides for the
      magnetite nanoparticles. We demonstrate a dependence of the binding affinity of
      the peptides on pH and buffer ions in two different experimental set-ups. The
      nature of surface coordination for glutamic acid-based peptides can be
      demonstrated with different spectroscopic approaches such as infrared
      spectroscopy (IR), Raman spectroscopy and circular dichroism spectroscopy (CD).
      We want to emphasise the importance of physicochemical properties such as surface
      energy, polarity, morphology and charge. These parameters, which are dependent on
      the environmental conditions, play a crucial role in peptide interactions with
      iron oxide surfaces. The understanding of the adsorption of simple biomolecules
      on nanoscale metal oxide surfaces also represents the key to the even more
      complex interactions of proteins at the bio-nano interface. From the
      identification of interaction patterns and an understanding of the adsorption of
      these peptides, the up-scaling to tagged model proteins facilitates the
      possibility of an industrial magnetic separation process and might therefore
      reduce time and costs in purification processes.

PMID- 28765850
TI  - Efficient 2D double-quantum solid-state NMR spectroscopy with large spectral
      widths.
AB  - 2D double-quantum single-quantum correlation spectra with arbitrary spectral
      widths can be recorded with SR26 and related supercycled recoupling sequences
      when applying Supercycle-Timing-Compensation (STiC) phase shifts. This concept
      widely extends the applicability of supercycled sequences, most importantly for
      obtaining long-range distance constraints for structure determination with solid
      state NMR.

PMID- 28765851
TI  - Ring opening polymerisation of lactide with uranium(iv) and cerium(iv)
      phosphinoaryloxide complexes.
AB  - The C3-symmetric uranium(iv) and cerium(iv) complexes Me3SiOM(OArP)3, M = U (1),
      Ce (2), OArP = OC6H2-6-tBu-4-Me-2-PPh2, have been prepared and the difference
      between these 4f and 5f congeners as initiators for the ring opening
      polymerisation (ROP) of l-lactide is compared. The poorly controlled reactivity
      of the homoleptic analogue U(OArP)4 (3) demonstrates the importance of the M
      OSiMe3 initiating group. The incorporation of a nickel atom in 1 to form the U-Ni
      heterobimetallic complex Me3SiOU(OArP)3Ni (4) may be the first example of the use
      of the inverse trans influence to switch the reactivity of a complex. This would
      imply the formation of the U-Ni bond strengthens the U-OSiMe3 bond to such an
      extent that the ROP catalysis is switched off. Changing the conditions to
      immortal polymerisation dramatically increases polymerisation rates, and switches
      the order, with the Ce complex now faster than the U analogue, suggesting ligand
      protonolysis to afford a more open coordination sphere. For the ROP of rac
      lactide, uranium complex 1 promotes heterotacticity at the highest levels of
      stereocontrol yet reported for an actinide complex.

PMID- 28765852
TI  - One-pot preparation of polymer microspheres having wrinkled hard surfaces through
      self-assembly of silica nanoparticles.
AB  - Polymer microspheres with wrinkled hard surfaces composed of self-assembled
      silica nanoparticles were prepared via suspension polymerization. The polymer
      surface morphology could be controlled by changing the silica nanoparticle
      concentration in the monomer droplets. The wrinkles could trap small polystyrene
      particles in their grooves, thus demonstrating viability in separation science.

PMID- 28765853
TI  - Cancer screening: concerns, controversy and evidence.

PMID- 28765854
TI  - PSA testing for men at average risk of prostate cancer.
AB  - Prostate-specific antigen (PSA) testing of men at normal risk of prostate cancer
      is one of the most contested issues in cancer screening. There is no formal
      screening program, but testing is common - arguably a practice that ran ahead of
      the evidence. Public and professional communication about PSA screening has been
      highly varied and potentially confusing for practitioners and patients alike.
      There has been much research and policy activity relating to PSA testing in
      recent years. Landmark randomised controlled trials have been reported;
      authorities - including the 2013 Prostate Cancer World Congress, the Prostate
      Cancer Foundation of Australia, Cancer Council Australia, and the National Health
      and Medical Research Council - have made or endorsed public statements and/or
      issued clinical practice guidelines; and the US Preventive Services Task Force is
      revising its recommendations. But disagreement continues. The contention is
      partly over what the new evidence means. It is also a result of different valuing
      and prioritisation of outcomes that are hard to compare: prostate cancer deaths
      prevented (a small and disputed number); prevention of metastatic disease
      (somewhat more common); and side-effects of treatment such as incontinence,
      impotence and bowel trouble (more common again). A sizeable proportion of men
      diagnosed through PSA testing (somewhere between 20% and 50%) would never have
      had prostate cancer symptoms sufficient to prompt investigation; many of these
      men are older, with competing comorbidities. It is a complex picture. Below are
      four viewpoints from expert participants in the evolving debate, commissioned for
      this cancer screening themed issue of Public Health Research & Practice. We asked
      the authors to respond to the challenge of PSA testing of asymptomatic, normal
      risk men. They raise important considerations: uncertainty, harms, the
      trustworthiness and interpretation of the evidence, cost (e.g. of using
      multiparametric magnetic resonance imaging to triage patients with elevated PSA),
      a likely bias towards intervention (particularly for cancer), and the potential
      to limit harm by treating more conservatively (although this may not occur
      consistently). They provide important insights, and disagree on some issues, but
      generally concur that men should decide for themselves whether to be tested. It
      seems reasonable to support men's autonomy to make their own decisions based on
      their own values. However, the support men might require to decide is likely to
      be considerable, and this needs to be taken seriously in policy making.

PMID- 28765855
TI  - What is overdiagnosis and why should we take it seriously in cancer screening?
AB  - Overdiagnosis occurs in a population when conditions are diagnosed correctly but
      the diagnosis produces an unfavourable balance between benefits and harms. In
      cancer screening, overdiagnosed cancers are those that did not need to be found
      because they would not have produced symptoms or led to premature death. These
      overdiagnosed cancers can be distinguished from false positives, which occur when
      an initial screening test suggests that a person is at high risk but follow-up
      testing shows them to be at normal risk. The cancers most likely to be
      overdiagnosed through screening are those of the prostate, thyroid, breast and
      lung. Overdiagnosis in cancer screening arises largely from the paradoxical
      problem that screening is most likely to find the slow-growing or dormant cancers
      that are least likely to harm us, and less likely to find the aggressive, fast
      growing cancers that cause cancer mortality. This central paradox has become
      clearer over recent decades. The more overdiagnosis is produced by a screening
      program, the less likely the program is to serve its ultimate goal of reducing
      illness and premature death from cancer. Thus, it is vital that health
      professionals and researchers continue an open, scientific inquiry into the
      extent and consequences of overdiagnosis, and devise appropriate responses to it.

PMID- 28765856
TI  - Shangri-La and the integration of mental health care in Australia.
AB  - We wanted the best, but it turned out like always. Victor Chernomydrin) 1
      According to literary legend, Shangri-La is an idyllic and harmonious place.
      Mental health is aspiring to its own Shangri-La in the shape of better integrated
      care. But do current reforms make integrated practice more or less likely? And
      what can be done to increase the chances of success? The aim of this article is
      to review the current state of mental health reforms in Australia now under way
      across Primary Health Networks, the National Disability Insurance Scheme,
      psychosocial support services and elsewhere. What are these changes and what are
      the implications for the future of integrated mental health care? Is Shangri-La
      just over the horizon, or have we embarked instead on a fool's errand?

PMID- 28765857
TI  - Why the public health sector couldn't create Pokemon Go.
AB  - Pokemon Go has been subject to much attention - from both the players that
      download the augmented reality game and the news media. Amid the exaggerated
      media reports, Pokemon Go may have unintended health benefits. Players have
      reported walking more, spending more time with family, experiencing improvements
      in their mental health and feeling more connected to their communities. It is
      hard to imagine public health researchers developing a similar game that is fun,
      taps into pop culture, reaches a wide target audience, makes use of physical and
      virtual environments, creates a sense of both competition and community, and has
      spin-off health benefits. Companies that endanger public health immediately
      recognised the value of the Pokemon Go app, and exploited it to advertise and
      promote consumption of unhealthy foods. Public health stakeholders need to
      develop mobile-based interventions within a framework that embraces pleasure,
      rewards, participation and community. Public health agencies need to be just as
      nimble and responsive as companies that are harmful to health, or forever be
      creating games that nobody plays.

PMID- 28765858
TI  - History, development and future of cancer screening in Australia.
AB  - INTRODUCTION: The aim of screening an asymptomatic population for cancer is to
      achieve better health outcomes, particularly a population survival benefit.
      Australia has three population screening programs: the National Cervical
      Screening Program (NCSP), BreastScreen Australia and the National Bowel Cancer
      Screening Program (NBCSP). METHODS: We reviewed the history and development of
      the three programs. NCSP: Women have a Pap smear every 2 years from age 18-20, or
      2 years after first becoming sexually active, until age 69. Since introduction of
      the NCSP, the cervical cancer incidence has halved, with an approximate 60%
      decrease in mortality. The screening participation rate approximates 57%, but is
      lower for Aboriginal and Torres Strait Islander women, women in remote areas, and
      women with lower socio-economic status. The National HPV (human papillomavirus)
      Vaccination Program, introduced in 2007, is expected to reduce the incidence of
      cervical cancer by a further 70% and has already reduced the incidence of high
      grade lesions in girls. In 2017, testing for HPV every 5 years starting at age 25
      will replace the Pap smear as the principal screening test. BreastScreen
      Australia: This program targets women aged 50-74. Over 20 years, mortality from
      breast cancer has decreased by 32% in response to screening and treatment
      advances. The participation rate is 56%. The major adverse impact of breast
      screening is overdiagnosis, estimated in Australia to be as low as 8% of detected
      cancers, but with estimates of up to 30% from some research. Women should be made
      aware of both the potential benefits and harms from screening. Genetic testing
      for BRCA1 and BRCA2 mutations in high-risk women leads to earlier screening.
      NBCSP: The NBCSP uses immunochemical faecal occult blood test (iFOBT) kits on
      stool samples to detect bleeding from the bowel. When rollout is complete in
      2020, test kits will be sent every 2 years to people aged 50-74. People who test
      positive are followed up with a colonoscopy. The participation rate is currently
      37%. The positivity rate is 7%, and stage 1 bowel cancer presentations have
      tripled since the program began. CONCLUSIONS: Research needs to focus on reducing
      mortality through increased screening participation and, in the future, obtaining
      guidance for customised screening from genomic testing.

PMID- 28765859
TI  - Clinical consultations and investigations before and after discontinuation of
      endocrine therapy in women with primary breast cancer.
AB  - OBJECTIVE: Although clinical trials recommend that women with hormone-dependent
      primary breast cancer remain on endocrine therapy for at least 5 years, up to 60%
      discontinue treatment early. We determined whether these women had consulted with
      clinicians or had investigations for cancer recurrence or metastasis around the
      time they discontinued endocrine therapy, and whether clinical contact continued
      after discontinuation. METHODS: We performed case-control and cohort studies of
      women from the 45 and Up Study who were diagnosed with invasive primary breast
      cancer between January 2003 and December 2008, and who had >=12 months of
      anastrozole, exemestane, letrozole or tamoxifen subsequently dispensed. RESULTS:
      Women who consulted general practitioners and surgeons/oncologists, and women who
      had breast ultrasound/mammogram were just as likely to discontinue endocrine
      therapy within 30 days as those who did not consult these clinicians or have this
      investigation. In the 6 months after early discontinuation, women who
      discontinued endocrine therapy were less likely to consult general practitioners
      (adjusted risk ratio [RRadj] 0.80; 95% confidence interval [CI] 0.75, 0.86) and
      surgeons/oncologists (RRadj 0.62; 95% CI 0.54, 0.72) than those who remained on
      therapy. CONCLUSIONS: For most women, endocrine therapy discontinuation did not
      appear to follow consultation with doctors managing their breast cancer treatment
      or investigations for recurrence or metastasis. However, women who discontinued
      endocrine therapy were less likely to consult their general practitioner or
      surgeon/oncologist in the 6 months following discontinuation than those who
      remained on therapy. Of the clinician groups studied, general practitioners are
      best placed to engage and support women to continue pharmacotherapy. However,
      mechanisms are needed to prompt clinicians to do this at every visit.

PMID- 28765860
TI  - Assessing the efficacy of cancer screening.
AB  - BACKGROUND: Population-based cancer screening has been established for several
      types of cancer in Australia and internationally. Screening may perform
      differently in practice from randomised controlled trials, which makes evaluating
      programs complex. MATERIALS AND METHODS: We discuss how to assess the evidence of
      benefits and harms of cancer screening, including the main biases that can
      mislead clinicians and policy makers (such as volunteer, lead-time, length-time
      and overdiagnosis bias). We also discuss ways in which communication of risks can
      inform or mislead the community. RESULTS: The evaluation of cancer screening
      programs should involve balancing the benefits and harms. When considering the
      overall worth of an intervention and allocation of scarce health resources,
      decisions should focus on the net benefits and be informed by systematic reviews.
      Communication of screening outcomes can be misleading. Many messages highlight
      the benefits while downplaying the harms, and often use relative risks and 5-year
      survival to persuade people to screen rather than support informed choice.
      LESSONS LEARNED: An evidence based approach is essential when evaluating and
      communicating the benefits and harms of cancer screening, to minimise misleading
      biases and the reliance on intuition.

PMID- 28765861
TI  - Improving communication about cancer screening: moving towards informed decision
      making.
AB  - For decades, public communications about cancer screening have used persuasive
      techniques with the aim of maximising the number of people being screened.
      However, perspectives have changed more recently to acknowledge that screening
      can lead to harm as well as benefit, and that it is important for service users
      to consider both. For some types of cancer screening, there is professional
      contention about whether benefits clearly outweigh harms. In light of this, an
      emerging trend in cancer screening communication is to try to support informed
      decision making - that is, to help people understand both the advantages and
      disadvantages of screening, allowing them to make individual decisions about
      their screening participation that reflect their informed preferences. In this
      review, we provide an overview of key theoretical and practical aspects of
      improving communication and supporting informed decision making about cancer
      screening, highlight relevant research and discuss future implications.

PMID- 28765862
TI  - Developing an alternative alcohol advertising complaint review system: lessons
      from a world-first public health advocacy initiative.
AB  - Young people in Australia are frequently exposed to alcohol marketing. Leading
      health organisations recommend legislative controls on alcohol advertising as
      part of a comprehensive approach to reduce alcohol-related harm. However,
      Australia relies largely on industry self-regulation. This paper describes the
      development and implementation of the Alcohol Advertising Review Board (AARB), a
      world-first public health advocacy initiative that encourages independent
      regulation of alcohol advertising. The AARB reviews complaints about alcohol
      advertising, and uses strategies such as media advocacy, community engagement and
      communicating with policy makers to highlight the need for effective regulation.
      In 4 years of operation, the AARB has received more complaints than the self
      regulatory system across a similar period. There has been encouraging movement
      towards stronger regulation of alcohol advertising. Key lessons include the
      importance of a strong code, credible review processes, gathering support from
      reputable organisations, and consideration of legal risks and sustainability. The
      AARB provides a unique model that could be replicated elsewhere.

PMID- 28765863
TI  - [Spontaneous pneumothorax in cats: two case reports and literature review].
AB  - Spontaneous pneumothorax (SP) is a non-traumatic accumulation of air in the
      pleural cavity. This case report describes a cat with SP as a result of primary
      pulmonary adenocarcinoma. A second cat was diagnosed with primary pulmonary
      adenocarcinoma and asthma. A thoracostomy tube was inserted in the first cat
      while in the second cat a thoracostomy tube was placed and lobectomy of the right
      cranial and middle lung lobes was performed. Both cats died following treatment.
      The current literature reviewed here covers the comparative etiologies of SP as
      well as clinical presentation, diagnostic work-up, therapy and prognosis in cats.
      A total of 64 cases of cats with secondary spontaneous pneumothorax reported in
      nine articles are discussed. To our knowledge, there has been no previous
      description in the literature regarding primary SP in cats. Based on prior case
      reports, surgery was performed in 16% (10 cats) of SP cases. The current review
      demonstrates that depending on the underlying lung disease, cats with SP have a
      careful short-term prognosis because 39 of 64 cats (60%) were discharged.

PMID- 28765864
TI  - Comparison of EHR-based diagnosis documentation locations to a gold standard for
      risk stratification in patients with multiple chronic conditions.
AB  - OBJECTIVE: To measure variation among four different Electronic Health Record
      (EHR) system documentation locations versus 'gold standard' manual chart review
      for risk stratification in patients with multiple chronic illnesses. METHODS:
      Adults seen in primary care with EHR evidence of at least one of 13 conditions
      were included. EHRs were manually reviewed to determine presence of active
      diagnoses, and risk scores were calculated using three different methodologies
      and five EHR documentation locations. Claims data were used to assess cost and
      utilization for the following year. Descriptive and diagnostic statistics were
      calculated for each EHR location. Criterion validity testing compared the gold
      standard verified diagnoses versus other EHR locations and risk scores in
      predicting future cost and utilization. RESULTS: Nine hundred patients had 2,179
      probable diagnoses. About 70% of the diagnoses from the EHR were verified by gold
      standard. For a subset of patients having baseline and prediction year data
      (n=750), modeling showed that the gold standard was the best predictor of
      outcomes on average for a subset of patients that had these data. However,
      combining all data sources together had nearly equivalent performance for
      prediction as the gold standard. CONCLUSIONS: EHR data locations were inaccurate
      30% of the time, leading to improvement in overall modeling from a gold standard
      from chart review for individual diagnoses. However, the impact on identification
      of the highest risk patients was minor, and combining data from different EHR
      locations was equivalent to gold standard performance. The reviewer's ability to
      identify a diagnosis as correct was influenced by a variety of factors, including
      completeness, temporality, and perceived accuracy of chart data.

PMID- 28765866
TI  - [Evaluation of nutritional characteristics of commercial canned cat diets].
AB  - OBJECTIVE: To evaluate commercial complete canned cat foods according to their
      composition, labeling and nutritional characteristics. MATERIALS AND METHODS: A
      total of 21 commercial complete canned compound feeds for adult cats were
      analyzed for crude nutrients, minerals, vitamins, selected amino acids and
      taurine. The analyzed parameters were compared to the internal set of standards
      of the European Pet Food Industry Federation (FEDIAF). The energy content was
      calculated and compared with the labeled recommendations regarding the amounts of
      diet that should be fed. Analyzed nutrients were compared with the labeled
      nutrients according to the regulations of the EU food and feed law (directive EU
      regulation 767/2009). RESULTS: In many cases, the labeled feeding protocols did
      not match the calculated daily energy requirements. In eight complete foods, the
      recommended daily feed amounts were underestimated and four recommendations
      exceeded energy requirements of adult cats. In 12 complete foods, the calcium and
      phosphorus contents were threefold higher than the respective requirement. In 16
      of 21 complete foods, substantial discrepancies were observed between the
      recommendations and the analyzed trace elements. In particular, selenium contents
      exceeded the selenium requirement more than threefold. The vitamin, arginine and
      taurine contents showed no significant discrepancies to the recommendations. With
      respect to the labeled nutrients, there were only minor deviations from the
      regulations of the European law. CONCLUSION AND CLINICAL RELEVANCE: In general,
      healthy adult cats are adequately supplied with energy and nutrients when feeding
      commercial canned complete diets for cats. In cases of body weight loss or gain,
      the labelled feed amounts should be questioned. The high phosphorus contents are
      an issue of concern, because a high phosphorus intake can potentially increase
      the risk for urinary stones and particularly for older cats the risk for renal
      insufficiency. Furthermore, it is recommended to decrease the high selenium
      levels by the reduction of selenium-rich feed materials such as offal.

PMID- 28765865
TI  - Long-term Patterns of Patient Portal Use for Pediatric Patients at an Academic
      Medical Center.
AB  - BACKGROUND: Patient portal adoption has increased over the last two decades. Most
      research about patient portals has focused on adult populations in the primary
      care and medical specialty settings. OBJECTIVE: We describe initial and long-term
      portal use by pediatric patients and their caregivers in a broadly deployed
      patient portal at an academic medical center. METHODS: We analyzed portal usage
      for pediatric patients and their caregivers from 2008 to 2014. We recorded usage
      events with time stamps; user role defined as self, surrogate (i.e., parent or
      guardian), or delegate; and functions accessed. Usage events were grouped into
      sessions to calculate descriptive statistics by patient age, user role, and
      active use over time. RESULTS: From 2008 to 2014, the number of portal accounts
      increased from 633 to 17,128. 15.9% of pediatric patients had their own account;
      93.6%, a surrogate account; and 2.2% a delegate account. During the study period,
      15,711 unique users initiated 493,753 sessions and accessed 1,491,237 functions.
      Most commonly used functions were secure messaging (accessed in 309,204 sessions;
      62.6%); test results (174,239; 35.3%) and appointments (104,830; 21.2%). Function
      usage was greatest for patients ages 0-2 years (136,245 functions accessed;
      23.1%) and 15-17 years (109,241;18.5%). Surrogate users conducted 83.2% of logins
      for adolescent patients. Portal accounts were actively used for < 1 year for
      9,551 patients (55.8%), 1-2 years for 2,826 patients (16.5%), 2-3 years for 1,968
      patients (11.5%) and over 3 years for 2,783 patients (16.3%). CONCLUSION:
      Pediatric patients and caregivers have avidly used messaging, test result, and
      appointment functions. The majority of access was done by surrogates. Adolescent
      portal usage increased with age. Most accounts for pediatric patients were only
      used actively for a few years, with peak usage for patients in early childhood
      and late adolescence.

PMID- 28765867
TI  - [Anthelmintic resistance in ruminants: development, diagnostics, and procedures].
AB  - Anthelmintic resistance of gastrointestinal nematodes in small ruminants, but
      also in cattle and horses, is now found worldwide. The reason for increasing
      anthelmintic resistance is, in particular, the extensive use of all the
      anthelmintic agents available on the market. A non-targeted use leads to the
      selection of naturally occurring resistance genes within parasite populations.
      The most practical method for evaluating the efficacy of an anthelmintic is the
      fecal egg-count reduction test. To reduce the rate of anthelmintic resistance
      development, the available active substances must be applied less and in a
      targeted manner. When applying targeted (selective) treatment, part of the herd
      is left untreated. Therefore, it is necessary to identify the animals that
      require treatment for health or economic reasons. To decide on anthelmintic
      treatment, findings can be collected from single animals or from a group of
      animals in a herd. To determine which groups of animals are to be treated within
      a herd (targeted treatment), pooled fecal samples (cattle and small ruminants),
      serum pepsinogen concentration (cattle), or Ostertagia ostertagi antibodies in
      the bulk milk (cattle) can be analyzed. For individual animal (targeted
      selective) treatment, criteria including fecal egg count (cattle and small
      ruminants), conjuctival color as an indicator for infection with Haemonchus
      contortus (FAMACHA(r), small ruminants), body condition in adult animals (small
      ruminants), weight gain in juvenile animals (cattle and small ruminants), and the
      consistency of the feces (small ruminants) are used. These decision criteria can
      also be combined to enhance the informative value. Furthermore, an efficacy test
      of the anthelmintics used should be performed regularly at the beginning of the
      pasture season. During the pasture season, a low infection pressure should be
      maintained by pasture management strategies. The goal of sustainable parasite
      management is the reduction of anthelmintic treatment while maintaining the
      productivity and health of the animals and thus a longer effectiveness of the
      available drugs.

PMID- 28765868
TI  - Individual variability in height tracking in infancy: comparison of two
      longitudinal data sets of children born in 1990 and 1996 in Vilnius, Lithuania.
AB  - ABSTRACT: The aim of this study was to investigate variability of individual
      trajectories for height in two different birth cohorts of Lithuanian infants.
      Data were derived from the personal health records of 781 (399 boys and 382
      girls) and 263 (139 boys and 124 girls) children born in 1990 and 1996
      (respectively) in the city of Vilnius in Lithuania. The height of each child at
      birth, at one year and two years of age was investigated. The analysis of growth
      tracking was performed tracing the main centiles for height (3, 10, 25, 50, 75,
      90 and 97). According to increase of height along the main centiles, five types
      of growth curves were possible. The average number of changed centile tracks for
      height for girls born in 1990, girls born in 1996 and boys born in 1996 was 2.05
      +/- 1.12, 2.02 +/- 1.25 and 2.03 +/- 1.06, respectively. However, the average
      number of changed centile tracks for height for boys born in 1990 was 1.74 +/-
      1.16, which differed significantly (p < 0.001) from the average number of changed
      centile tracks for height for girls born in 1990 and 1996, and boys born in 1996.
      Statistically significant differences (p < 0.001) were obtained between the
      incidences of the stable type of growth curve: the boys born in 1996 have
      presented the aforementioned type of growth curve much rarer compared to both the
      girls born in the same year and the boys born in 1990.

PMID- 28765869
TI  - Use of units of measurement error in anthropometric comparisons.
AB  - ABSTRACT: Anthropometrists attempt to minimise measurement errors, however,
      errors cannot be eliminated entirely. Currently, measurement errors are simply
      reported. Measurement errors should be included into analyses of anthropometric
      data. This study proposes a method which incorporates measurement errors into
      reported values, replacing metric units with 'units of technical error of
      measurement (TEM)' by applying these to forensics, industrial anthropometry and
      biological variation. The USA armed forces anthropometric survey (ANSUR) contains
      132 anthropometric dimensions of 3982 individuals. Concepts of duplication and
      Euclidean distance calculations were applied to the forensic-style identification
      of individuals in this survey. The National Size and Shape Survey of Australia
      contains 65 anthropometric measurements of 1265 women. This sample was used to
      show how a woman's body measurements expressed in TEM could be 'matched' to
      standard clothing sizes. Euclidean distances show that two sets of repeated
      anthropometric measurements of the same person cannot be matched (> 0) on
      measurements expressed in millimetres but can in units of TEM (= 0). Only 81
      women can fit into any standard clothing size when matched using centimetres,
      with units of TEM, 1944 women fit. The proposed method can be applied to all
      fields that use anthropometry. Units of TEM are considered a more reliable unit
      of measurement for comparisons.

PMID- 28765870
TI  - The relationship of cranial, orbital and nasal cavity size with the morphology of
      the supraorbital region in modern Homo sapiens.
AB  - ABSTRACT: Morphological variation of the supraorbital region (SR) in human crania
      has been investigated and its potential sources suggested, along with the
      importance of the size of the facial skeleton, neurocranium, and orbit for the
      formation of this region. However, previous studies have not indicated whether
      facial size exhibits a stronger association with SR robusticity than neurocranial
      size or sex; moreover, the association between orbital volume and SR robusticity
      has been analysed only in non-human primate skulls. In this study we investigate
      whether the size of the facial skeleton, neurocranium, two measures of relative
      orbital size (orbital volume and estimated orbital aperture area), the relative
      size of the nasal cavity, and the relative estimated area of the anterior nasal
      cavity opening are related to SR robusticity; we also examine which of these
      analysed relationships is strongest, as well as independent of the influence of
      the other traits, in a geographically diverse modern human cranial sample. The
      results of Spearman's rank and partial rank correlations (encompassing models
      including or excluding sex and geographic origin) show a relationship between
      most of the above-mentioned variables and SR robusticity, with the exception of
      the estimated relative area of the orbital opening (in the case of the results of
      Spearman's rank correlations) and the traits of the nasal cavity. Of all the
      analysed traits, sex appears to be the most important for the formation of SR
      robusticity and, of two measures of cranial size, neurocranial size was the most
      significant. The strong relationship between SR robusticity and relative orbital
      volume was observed in models without the geographic origin factor. The results
      concerning analysed models suggest the influence of this factor on this
      relationship; however, to explain this influence, further studies are needed.

PMID- 28765871
TI  - Biometric sex estimation using the scapula and clavicle in a modern Greek
      population.
AB  - ABSTRACT: Human skeletal remains exhibit sexual dimorphism, which is apparent in
      adult living individuals as well. Researchers from forensic and
      osteoarchaeological fields have a growing interest in establishing metric
      standards for sexing by use of discriminant function analysis. The present study
      focuses on providing sex estimation metric standards using measurements from the
      scapula and clavicle in a Modern Greek sample (Athens Collection) consisting of
      107 male and 90 female skeletons. A total of seven measurements were taken:
      maximum scapular height and breadth, glenoid cavity height and breadth, maximum
      clavicular length, anterior and superior clavicular diameter. The calculation of
      Sexual Dimorphism Index showed a significant degree of sexual dimorphism on both
      bones ranging from 10% to 18%. Statistical analysis provided the discriminant
      functions with an accuracy of correct sex estimation between 84.9% and 91.4%, and
      showed that the highest accuracy rate was obtained from the left scapula
      measurements; proving that this bone can be a useful tool in providing an
      accurate sex estimation in skeletal remains of Modern Greek origin.

PMID- 28765872
TI  - Impact of normal weight obesity on fundamental motor skills in pre-school
      children aged 3 to 6 years.
AB  - ABSTRACT: Normal weight obesity is defined as having excessive body fat, but
      normal BMI. Even though previous research revealed that excessive body fat in
      children inhibited their physical activity and decreased motor performance, there
      has been only little evidence about motor performance of normal weight obese
      children. This study aims to establish whether normal weight obese pre-school
      children aged 3-6 years will have a significantly worse level of fundamental
      motor skills compared to normal weight non-obese counterparts. The research
      sample consisted of 152 pre-schoolers selected from a specific district of
      Prague, the Czech Republic. According to values from four skinfolds: triceps,
      subscapula, suprailiaca, calf, and BMI three categories of children aged 3-6
      years were determined: A) normal weight obese n = 51; B) normal weight non-obese
      n = 52; C) overweight and obese n = 49. The Movement Assessment Battery for
      Children (MABC-2) was used for the assessment of fundamental motor skills. Normal
      weight obese children had significantly higher amount of adipose tissue p < 0.001
      than normal weight non-obese children but the same average BMI. Moreover, normal
      weight obese children did not have significantly less amount of subcutaneous fat
      on triceps and calf compared to their overweight and obese peers. In majority of
      MABC-2 tests, normal weight obese pre-schoolers showed the poorest performance.
      Moreover, normal weight obese children had significantly worse total standard
      score = 38.82 compared to normal weight non-obese peers = 52.27; p < 0.05. In
      addition, normal weight obese children had a more than three times higher
      frequency OR = 3.69 CI95% (1.10; 12.35) of severe motor deficit performance <=
      5th centile of the MABC-2 norm. These findings are strongly alarming since
      indices like BMI are not able to identify normal weight obese individual. We
      recommend verifying real portion of normal weight obese children as they are
      probably in higher risk of health and motor problems than overweight and obese
      population due to their low lean mass.

PMID- 28765873
TI  - Classification of cancer cell lines using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and statistical analysis.
AB  - Over the past decade, matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF MS) has been established as a valuable platform for
      microbial identification, and it is also frequently applied in biology and
      clinical studies to identify new markers expressed in pathological conditions.
      The aim of the present study was to assess the potential of using this approach
      for the classification of cancer cell lines as a quantifiable method for the
      proteomic profiling of cellular organelles. Intact protein extracts isolated from
      different tumor cell lines (human and murine) were analyzed using MALDI-TOF MS
      and the obtained mass lists were processed using principle component analysis
      (PCA) within Bruker Biotyper(r) software. Furthermore, reference spectra were
      created for each cell line and were used for classification. Based on the intact
      protein profiles, we were able to differentiate and classify six cancer cell
      lines: two murine melanoma (B16-F0 and B164A5), one human melanoma (A375), two
      human breast carcinoma (MCF7 and MDA-MB-231) and one human liver carcinoma
      (HepG2). The cell lines were classified according to cancer type and the species
      they originated from, as well as by their metastatic potential, offering the
      possibility to differentiate non-invasive from invasive cells. The obtained
      results pave the way for developing a broad-based strategy for the identification
      and classification of cancer cells.

PMID- 28765874
TI  - Upregulation of nuclear factor-kappaB and acid sensing ion channel 3 in dorsal
      root ganglion following application of nucleus pulposus onto the nerve root in
      rats.
AB  - The nucleus pulposus (NP) is an avascular, hydrated tissue that permits the
      intervertebral disc to resist compressive loads to the spine. To determine the
      mechanisms by which intervertebral disc degeneration is caused by the nucleus
      pulposus, the expression and regulation of nuclear factor (NF)-kappaB and acid
      sensing ion channel 3 (ASIC3) were examined. For the intervertebral disc
      degeneration model, NP was harvested from the tail of rats and applied to the L5
      dorsal root ganglion (DRG). The mechanical pain withdrawal threshold (PWT) in NP
      model rats was assessed. Reverse transcription-quantitative polymerase chain
      reaction and western blotting were used to examine NF-kappaB and ASIC3 expression
      levels in DRG. Finally, the effect of the NF-kappaB inhibitor pyrrolidine
      dithiocarbamate (PDTC) and the ASIC3 signaling pathway blocker amiloride were
      examined. Rats exposed to NP exhibited decreased PWT for 12 days, and NF-kappaB
      and ASIC3 was upregulated in DRG induced by NP 14 days after surgery. After
      administration of amiloride and PDTC to DRG affected by NP, the levels of nitric
      oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), NF
      kappaB and ASIC3 were downregulated, and the levels of aquaporin (AQP) 1 and AQP3
      were significantly increased for 14 days. In conclusion, these results suggested
      that NF-kappaB and ASIC3 may serve an important role in intervertebral disc
      degeneration caused by NP.

PMID- 28765875
TI  - Quantum dot/pMHC multimers vs. phycoerythrin/pMHC tetramers for identification of
      HLA-A*0201-restricted pHBV core antigen18-27-specific T cells.
AB  - Detection of human leukocyte antigens-A2-restricted p-hepatitis B virus (HBV)
      core antigen-specific cytotoxic T lymphocytes (CTLs) is important in the study of
      HBV immunopathogenesis and vaccine design. Currently, major histocompatibility
      complex (MHC) class I/peptide-(p) MHCI tetramers are considered the optimal tools
      to detect antigen-specific CTLs. However, the MHC-tetramer technique also has
      certain drawbacks and is under continuous development. The quantum dot (QD)
      bioconjugates nanotechnology with its unique inorganic-biological properties has
      been developing fast. However, QD/pMHC multimers have seldom been used for the
      identification of the C18-27 epitope, which is important in HBV infection.
      QD/pMHC multimers were synthesized by metal-affinity coordination and an avidin
      biotin system. In the present study they were characterized by transmission
      electron microscopy, dynamic light scattering and fluorescence spectrophotometry.
      C18-27-specific CTLs were obtained by ex vivo expansion of CD8+ T cells. Cultured
      CTLs were tested for the secretion level of interferon (IFN)-gamma by ELISA and
      for cytotoxicity by lactate dehydrogenase release assay. Then, the performance of
      phycoerythrin (PE)/pMHC tetramers and QD/pMHC multimers were compared by flow
      cytometry. The synthesized QD/pMHC multimers dispersed well and their emission
      spectrum exhibited only slight differences compared with original QDs. C18-27
      specific CTLs not only secreted IFN-gamma but also effectively targeted T2 cells
      pulsed with peptide C18-27. The frequencies of C18-27-specific CTLs determined by
      QD/pMHC multimers were higher compared with PE/pMHC tetramers. The present
      results suggested that QD/pMHC multimers may be able to characterize greater
      numbers of C18-27-specific CTLs with increased sensitivity compared to
      conventional strategies.

PMID- 28765876
TI  - Exogenous lipids promote the growth of breast cancer cells via CD36.
AB  - Cancer cells present sustained de novo fatty acid (FA) synthesis with increased
      production of saturated fatty acids (SFAs) and monounsaturated fatty acids
      (MUFAs). This change in FA metabolism is associated with overexpression of
      stearoyl-CoA desaturase 1 (SCD1), which catalyses the transformation of SFAs into
      MUFAs (e.g., oleic acid). In this study, we provide new evidence that SCD1
      inhibition leads to the anti-proliferation effect of breast cancer cells through
      induction of apoptosis, cell cycle arrest and migration prevention. However, the
      antitumor effect of the SCD1 inhibitor can be reversed by exogenous oleic acid.
      We hypothesize that, in addition to de novo synthesis, cancer cells may uptake
      exogenous FAs actively. CD36, also known as FA translocase (FAT), that functions
      as a transmembrane protein and mediates the uptake of FAs, is observed to be
      highly expressed in breast cancer tissues. Furthermore, the anti-proliferation
      effect caused by the SCD1 inhibitor can not be reversed by exogenous oleic acid
      supplementation in CD36 knockdown breast cancer cells. Our study revealed that
      the lipid metabolism of breast cancer is regulated not only by de novo
      lipogenesis but also by the availability of lipids outside cancer cells.
      Consistent with FA synthesis, FA uptake and transport will be another important
      target pathway for anticancer therapy, and the FA channel protein CD36 may
      provide a promising therapeutic target. Lipogenesis combined with FA transport
      will be a new orientation for antitumor therapy.

PMID- 28765877
TI  - Investigation of the immunomodulatory activity of Tricholoma matsutake mycelium
      in cyclophosphamide-induced immunosuppressed mice.
AB  - Tricholoma matsutake, a popular food and biopharmaceutical resource in Asia,
      possesses various pharmacological activities. Although T. matsutake mycelium (TM)
      may enhance immunity, previous studies, to the best of our knowledge, have been
      performed on normal animals or cells alone. The present study aimed to evaluate
      the immunomodulatory activity of TM at doses of 0.3, 1.0 and 2.0 g/kg in
      cyclophosphamide (CTX)-induced immunosuppressed mouse models. TM treatment for 2
      weeks markedly improved the gain in bodyweight, increased organ indices, reduced
      hind paw swelling and positively regulated the cytotoxicity of natural killer
      cells and the proliferation of lymphocytes. These effects are similar to that of
      thymosin alpha1 (0.16 mg/kg) which served as the positive control. In CTX-induced
      immunosuppressed mice, TM demonstrated marked effects on the modulation of the
      production of immunoglobulin (Ig)G and IgA, and the levels of interleukin-2, 6,
      10 and 12, interferon-alpha and gamma and tumor necrosis factor-alpha in serum.
      Compared with CTX mice, the reduced activity of nuclear factor (NF)-kappaB in
      serum and spleen, and phosphorylation of inhibitor of NF-kappaB kinase alpha/beta
      in spleen were observed in TM-treated mice. Taken together, TM effectively
      improved immune function in immunosuppressed mice via modulation of ILs and
      inflammatory factors associated with the NF-kappaB signaling pathway.

PMID- 28765878
TI  - Grifola frondosa polysaccharides induce breast cancer cell apoptosis via the
      mitochondrial-dependent apoptotic pathway.
AB  - Grifola frondosa, a type of food and medical fungus, has been shown to exhibit
      various pharmacological activities, including anticancer effects. As the most
      typical cancer diagnosed among female patients, breast cancer remains a huge
      concern threatening human health globally. In the present study, the anti-breast
      cancer effects of Grifola frondosa polysaccharides (GFPs) and the underlying
      mechanisms were investigated in MCF-7 and MDA-MB-231 cells, as well as in nude
      mice bearing MCF-7 tumor xenografts. GFPs exerted cytotoxic effects on the cells,
      as indicated by a decrease in cell viability, and an increase in the apoptototic
      rate, lactate dehydrogenase release and reactive oxygen species accumulation,
      inducing mitochondrial dysfunction. The increased expression of Bax, cleaved
      caspase-3 and caspase-8, and the reduced levels of B-cell lymphoma 2 (Bcl-2) and
      Bcl-extra large (Bcl-xL) were observed in the cells incubated with GFPs and in
      the tumor tissues of the mice treated with GFPs. Moreover, the GFPs significantly
      suppressed the phosphorylation of AKT/glycogen synthase kinase-3beta and
      extracellular signal-regulated kinases in a time-dependent manner. Finally, the
      inhibition of MCF-7 tumor xenograft growth further confirmed the anti-breast
      cancer effects of GFPs. All these findings revealed that GFPs induced human
      breast cancer cell apoptosis via the mitochondrial-dependent apoptotic pathway,
      and provide experimental evidence to support the use of Grifola frondosa as a
      potential treatment for breast cancer.

PMID- 28765880
TI  - MicroRNA-494 inhibits nerve growth factor-induced cell proliferation by targeting
      cyclin D1 in human corneal epithelial cells.
AB  - Nerve growth factor (NGF) is expressed in the human corneal epithelium and
      stroma. It is an efficient therapy for human corneal ulcers caused by neurotropic
      disease. However, little is known about the molecular mechanism of NGF in healing
      human corneal epithelial diseases. Numerous microRNAs (miRNAs) are expressed in
      the cornea and miRNAs have important roles in regulating corneal development. In
      the present study, novel miRNA regulators were demonstrated to be involved in NGF
      induced human corneal epithelial cell (hCEC) proliferation. NGF treatment
      significantly downregulated the expression of miRNA-494 in hCECs in vitro.
      Furthermore, miRNA-494 increased G1 arrest in the immortalized human corneal
      epithelial cell (ihCEC) line and suppressed cell proliferation. Accordingly,
      bioinformatics programs and luciferase reporter assay demonstrated that miRNA-494
      directly targeted cyclin D1 by binding to a sequence in the 3'-untranslated
      region. In addition, overexpression of miRNA-494 decreased both basal and NGF
      induced cyclin D1 expression. NGF treatment partially suppressed miRNA-494
      expression and restored cyclin D1 expression. Furthermore, co-transfection of
      miRNA-494 with the cyclin D1 ORF clone partially restored cyclin D1 mRNA and
      protein expression. These findings indicate that miRNA-494 and its target cyclin
      D1 may be a crucial axis for NGF in regulating the proliferation of hCEC.
      Specific modulation of miRNA-494 in hCEC could represent an attractive approach
      for treating cornea epithelial diseases.

PMID- 28765879
TI  - Mass spectrometric identification of dystrophin, the protein product of the
      Duchenne muscular dystrophy gene, in distinct muscle surface membranes.
AB  - Supramolecular membrane complexes of low abundance are difficult to study by
      routine bioanalytical techniques. The plasmalemmal complex consisting of
      sarcoglycans, dystroglycans, dystrobrevins and syntrophins, which is closely
      associated with the membrane cytoskeletal protein dystrophin, represents such a
      high-molecular-mass protein assembly in skeletal muscles. The almost complete
      loss of the dystrophin isoform Dp427-M and concomitant reduction in the
      dystrophin-associated glycoprotein complex is the underlying cause of the highly
      progressive neuromuscular disorder named Duchenne muscular dystrophy. This gives
      the detailed characterization of the dystrophin complex considerable
      pathophysiological importance. In order to carry out a comprehensive mass
      spectrometric identification of the dystrophin-glycoprotein complex, in this
      study, we used extensive subcellular fractionation and enrichment procedures
      prior to subproteomic analysis. Mass spectrometry identified high levels of full
      length dystrophin isoform Dp427-M, alpha/beta-dystroglycans,
      alpha/beta/gamma/delta-sarcoglycans, alpha1/beta1/beta2-syntrophins and
      alpha/beta-dystrobrevins in highly purified sarcolemma vesicles. By contrast,
      lower levels were detected in transverse tubules and no components of the
      dystrophin complex were identified in triads. For comparative purposes, the
      presence of organellar marker proteins was studied in crude surface membrane
      preparations vs. enriched fractions from the sarcolemma, transverse tubules and
      triad junctions using gradient gel electrophoresis and on-membrane digestion.
      This involved the subproteomic assessment of various ion-regulatory proteins and
      excitation-contraction coupling components. The comparative profiling of skeletal
      muscle fractions established a relatively restricted subcellular localization of
      the dystrophin-glycoprotein complex in the muscle fibre periphery by proteomic
      means and clearly demonstrated the absence of dystrophin from triad junctions by
      sensitive mass spectrometric analysis.

PMID- 28765883
TI  - [Corrigendum] Transcriptome sequencing of human breast cancer reveals aberrant
      intronic transcription in amplicons and dysregulation of alternative splicing
      with major therapeutic implications.
AB  - After the publication of the article, the authors retrospectively noted that the
      name of Dr Dawn Jones, a postdoctoral researcher in the laboratory of Professor
      Christine Gosden, should have been added to the authors' list, whose contribution
      to the study greatly augmented the exploration of all the RNA products via
      adoption of the RNASeq (Illumina) methodology. All the existing authors agree to
      the inclusion of Dr Jones as a co-author, with the exception of Derek Gardener,
      who has retired from the Institute and is no longer contactable by e-mail
      (although we are confident that he would not raise any objection). The correct
      author list (and affiliations) should therefore have been published as follows:
      Shiva Seyed Forootan1, Joe M. Butler1, Derek Gardener1, Dawn Jones1, Alison E.
      Baird1, Andrew Dodson1, Alistair Darby2, John Kenny2, Neil Hall2, Andrew R.
      Cossins2, Christopher S. Foster1,3 and Christine M. Gosden1 1Molecular Pathology
      Laboratory, Department of Molecular and Clinical Cancer Medicine, Institute of
      Translational Medicine, Faculty of Health and Life Sciences, University of
      Liverpool, Royal Liverpool University Hospital, Liverpool L69 3GA; 2Center for
      Genomic Research, University of Liverpool, Liverpool L69 7ZB; 3HCA International,
      Pathology Laboratories, London WC1E 6JA, UK. We regret the oversight of having
      failed to include Dr Dawn Jones as an author on this paper. [the original article
      was published in the International Journal of Oncology 48: 130-144, 2016; DOI:
      10.3892/ijo.2015.3222].

PMID- 28765882
TI  - MicroRNA-300 decreases cell viability, inhibits migration and promotes apoptosis
      of osteosarcoma cells via downregulation of Twist1.
AB  - Osteosarcoma (OS) is the most frequently occurring pediatric bone malignancy in
      the world. Numerous miRNAs have previously been demonstrated to participate in
      the initiation and development of OS. The present study aimed to reveal the role
      of microRNA-300 (miR-300) in OS cells and elucidate the underlying mechanism
      involved. The expression of miR-300 in the MG63 human OS cell line was monitored
      via quantitative polymerase chain reaction (qPCR). Following transfection with
      miR-300 mimic, miR-300 inhibitor or scramble control, MG63 cell viability,
      migration and apoptosis were respectively measured by 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyltetrazolium bromide (MTT), modified two-chamber migration
      assay and flow cytometry. Dual-Luciferase reporter assays, qPCR and western blot
      analysis were subsequently performed to verify whether Twist1 was a direct target
      of miR-300. Furthermore, the expression levels of nuclear factor (NF)-kappaB
      pathway proteins were detected via western blot analysis. In MG63 cells, miR-300
      was effectively overexpressed or suppressed by transfection with miR-300 mimic or
      inhibitor, respectively (P<0.001). Overexpression of miR-300 significantly
      suppressed cell viability and migration, whereas it enhanced apoptotic rate
      (P<0.001). miR-300 suppression exhibited contrary results (P<0.05, P<0.01 or
      P<0.001). Twist1 was demonstrated to act as a direct target of miR-300, and was
      negatively regulated by miR-300. In addition, miR-300 overexpression
      downregulated the expression of the primary factors involved in the NF-kappaB
      signaling pathway. These effects on OS cell proliferation and apoptosis may be
      due to the miR-300 targeting of Twist1 and the suppressive effect on the NF
      kappaB signaling pathway.

PMID- 28765881
TI  - Identification of differentially expressed microRNAs in knee anterior cruciate
      ligament tissues surgically removed from patients with osteoarthritis.
AB  - The degradation of cruciate ligaments is frequently observed in degenerative
      joint diseases, such as osteo-arthritis (OA). The present study aimed to identify
      the differentially expressed microRNAs (miRNAs or miRs) in knee anterior cruciate
      ligament (ACL) tissues derived from patients with OA and in health subjects (non
      OA). By using Affymetrix miRNA 4.0 microarrays, a total of 22 miRNAs (including
      let-7f-5p, miR-26b-5p and miR-146a-5p) were found to be upregulated, while 17
      (including miR-18a-3p, miR-138-5p and miR-485-3p) were downregulated in the
      osteoarthritic ACL tissues (fold change >=2, P-value <0.05). The expression
      levels of 12 miRNAs were validated by quantitative PCR, and the corresponding
      results revealed an excellent correlation with the microarray data (R2=0.889).
      Genes (such as a disintegrin and metalloproteinase domain with thrombospondin
      type-1 motifs, bone morphogenetic protein-2, runt related transcription factor-2,
      collagen-1A1 and 2, interleukin-6 and transforming growth factor-beta) involved
      in cartilage development and remodeling, collagen biosynthesis and degradation,
      inflammatory response and extracellular matrix homeostasis were predicted as
      potential targets of the dysregulated miRNAs. Moreover, a large set of putative
      genes were enriched in OA pathogenesis-associated pathways (such as mitogen
      activated protein kinase and vascular endothelial growth factor signaling
      pathway). Collectively, the data from our study provides novel insight into the
      ligament injury-related miRNA dysregulation in patients with OA.

PMID- 28765884
TI  - Enhanced expression of natriuretic peptide receptor A and B in neutrophils of
      culprit lesions in patients with acute myocardial infarction.
AB  - Natriuretic peptides and their specific receptors have been suggested to have
      regulatory effects on smooth muscle cell (SMC) growth and inflammatory cell
      reactions. However, the roles of natriuretic peptide receptor A (NPR-A) and B
      (NPR-B) in unstable plaques remain to be studied in detail. Frozen sections from
      82 coronary artery segments were used. These segments were obtained at autopsy
      from 13 patients with acute myocardial infarction (AMI; 7 ruptured and 6 eroded
      plaques) and from 30 patients with non-cardiovascular diseases. Antibodies
      against SMCs, endothelial cells, macrophages, neutrophils, NPR-A, NPR-B and
      neutral endopeptidase (NEP) were used. Neutrophil infiltration was identified in
      all lesions with plaque rupture or erosion. Double immunostaining identified that
      the majority of NPR-A- or NPR-B-positive cells were neutrophils in ruptured and
      eroded plaques. Using morphometric analysis, no significant difference was
      observed in the percentage of NPR-A- and NPR-B-positive cells between ruptured
      and eroded plaques, while the number of NEP-positive neutrophils in ruptured
      plaques was significantly higher compared with eroded plaques (P<0.0001). These
      results of the distinct presence of NPR-A- and NPR-B-positive cells in unstable
      plaques underlying AMI suggested that natriuretic peptides serve a role in
      regulating plaque instability in humans.

PMID- 28765885
TI  - Anti-angiogenic properties of artemisinin derivatives (Review).
AB  - Angiogenesis, the process involving the development of new blood vessels from
      existing capillaries, is critical for growth and wound healing. However,
      pathological angiogenesis contributes to the pathogeneses of numerous diseases,
      including cancer, rheumatoid arthritis, diabetic retinopathy and macular
      degeneration. Hence, the inhibition of angiogenesis is an effective therapeutic
      approach for these diseases. Apart from its anti-malarial properties, artemisinin
      and its derivatives also exhibit potent anti-angiogenic properties. The molecular
      mechanisms underlying their inhibitory effects on angiogenesis have been studied
      by several groups. These investigations have revealed that artemisinins inhibit
      angiogenesis via the perturbations of cellular signaling pathways involved in the
      regulation of angiogenesis. Along with a brief introduction to artemisinin
      derivatives, this review provides a detailed summary of the effects of
      artemisinins on the mitogen-activated protein kinase (MAPK) pathway, the nuclear
      factor-kappaB (NF-kappaB) pathway and the phosphatidylinositide 3-kinase
      (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Due
      to the multiplicity of their actions on relevant signaling pathways, artemisinins
      are promising candidates with potential for use as anti-angiogenic agents for the
      treatment of related diseases or disorders.

PMID- 28765886
TI  - Exogenous spermine preserves mitochondrial bioenergetics via regulating Src
      kinase signaling in the spinal cord.
AB  - Regulation of mitochondrial metabolism is becoming an important target in
      inhibiting necrosis and apoptosis following secondary spinal cord injury, and
      physiological compounds that reduce mitochondrial dysfunction are regarded as
      efficient protective reagents following injury. It has been demonstrated that
      spermine, a polyamine composed of four primary amines, may be taken up by a
      mitochondria-specific uniporter and may preserve mitochondrial bioenergetics,
      suggesting that it may be important in the pathophysiology of mitochondria.
      However, the protective mechanism has not yet been definitively clarified. In the
      present study, isolated spinal cord mitochondria were incubated with spermine to
      evaluate its physiological functions and Src kinase activities. The results
      revealed that spermine increased oxidative phosphorylation, attenuated
      mitochondrial swelling and maintained the membrane potential. An inhibitor of Src
      kinases, amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2),
      markedly reduced the effects of spermine. However, inhibition of tyrosine
      phosphatases by vanadate led to marginal increases in the effects of spermine.
      Therefore, the present study hypothesized that tyrosine phosphorylation sites are
      present in the subunits of respiratory chains and mitochondrial permeability
      transition pore proteins, which may be modified via phosphorylation and
      dephosphorylation. Furthermore, spermine may upregulate the phosphorylation of
      Src kinases, and PP2 and vanadate conversely regulate Src phosphorylation. The
      results of the present study suggest that spermine is a strategic regulator
      within mitochondria that may activate Src kinases in the spinal cord, and
      tyrosine phosphorylation signaling is a primary regulatory pathway of
      mitochondrial metabolism.

PMID- 28765887
TI  - Down-regulation of long noncoding RNA RP11-713B9.1 contributes to the cell
      viability in non-small cell lung cancer (NSCLC).
AB  - Early diagnosis is essential to reduce lung cancer-associated morbidity and
      mortality rates; however the lack of diagnostic biomarkers for lung cancer has
      made this difficult. Recent studies have demonstrated that long noncoding RNAs
      (lncRNAs) serve important roles in cancer occurrence and progression. The present
      study investigated the novel lncRNA RP11-713B9.1, which is the antisense
      transcript of tumor suppressor in lung cancer 1 (TSLC1). The expression levels of
      RP11-713B9.1 and TSLC1 in non-small cell lung cancer were determined using
      reverse-transcription quantitative polymerase chain reaction, which revealed that
      the expression of RP11-713B9.1 and TSLC1 was significantly downregulated in tumor
      tissue compared with that in adjacent normal tissue samples. In addition, the
      expression of RP11-713B9.1 was identified to be positively correlated with the
      expression of tumor suppressors TSLC1, CYLD lysine 63 deubiquitinase and APC WNT
      signaling pathway regulator, and negatively correlated with B-Raf proto-oncogene
      serine/threonine kinase expression. Furthermore, the overexpression of RP11
      713B9.1 resulted in significant upregulation of TSLC1 and inhibition of H460 cell
      viability, while the opposite effects were observed following the knockdown of
      RP11-713B9.1 in A549 cells. Taken together, the results of the current study
      suggest that lncRNA RP11-713B9.1 serves as a promising biomarker and potential
      therapeutic target for non-small cell lung cancer.

PMID- 28765888
TI  - EDIL3 knockdown inhibits retinal angiogenesis through the induction of cell cycle
      arrest in vitro.
AB  - Pathological retinal angiogenesis is one of the most common causes of blindness,
      with limited treatment options being currently available. Epidermal growth factor
      (EGF)-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) has
      been reported to serve an important role in embryonic vasculogenesis and tumor
      angiogenesis; however, its implication in retinal angiogenesis has yet to be
      elucidated. The present study aimed to investigate the putative roles of EDIL3 in
      retinal endothelial cells. RNA interference was used to disrupt the expression of
      EDIL3 in human retinal endothelial cells (HRECs) in vitro, and the resulting
      effects were examined. Cell proliferation was assessed using cell counting kit-8
      reagent, Cell migration was investigated using a transwell chamber and a tube
      formation assay was used to study angiogenic capability in vitro. Flow cytometry
      was used to detect the cell cycle distribution and western blotting was used to
      study protein expression. The present results demonstrated that silencing EDIL3
      expression significantly impaired the proliferative, migratory and tube forming
      capabilities of HRECs. Furthermore, EDIL3 knockdown was revealed to induce cell
      cycle arrest at the G1 phase. Western blot analysis suggested that the possible
      mechanisms underlying the antiproliferative effects of EDIL3 silencing may
      involve the inhibition of EGF receptor-mediated pathways, and the suppression of
      cyclin D1 and cyclin E1 expression in HRECs. In conclusion, the findings of the
      present study suggested that EDIL3 may be implicated in retinal angiogenesis, and
      may have potential as a novel therapeutic target for the treatment of
      pathological angiogenesis.

PMID- 28765889
TI  - Downregulation of microRNA-143 promotes cell proliferation by regulating
      PKCepsilon in hepatocellular carcinoma cells.
AB  - The abnormal expression of microRNAs (miRNAs) has been reported in hepatocellular
      carcinoma (HCC), however, the functional role of miR-143 in HCC remains to be
      fully elucidated. The present study aimed to investigate the effects of the
      downregulation of miR-143 on HCC cell proliferation and apoptosis, and elucidated
      the underlying mechanism. Hepg2 and Hep3B human hepatoma cell lines cells were
      transfected with miR-143 inhibitor. Following transfection, the cell viability
      and apoptosis were respectively determined using a 3-(4, 5-dimethyl-2-thiazolyl)
      2, 5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, and the mRNA and
      protein levels of protein kinase Cepsilon (PKCepsilon) were examined. The
      expression levels of PKCepsilon were downregulated by short hairpin (sh)RNA, and
      the effects of the downregulation of miR-143 on HCC cell proliferation were
      measured. The results showed that the miR-143 inhibitor significantly promoted
      cell proliferation and suppressed apoptosis in the Hepg2 and Hep3B cells. The miR
      143 inhibitor significantly increased the protein levels of PKCepsilon in the
      Hepg2 and Hep3B cells; however, no significant differences were found in the mRNA
      levels of PKCepsilon. In addition, the downregulation of PKCepsilon markedly
      decreased the cell viability of the Hepg2 and Hep3B cells, and co-transfection
      with the miR-143 inhibitor and PKCepsilon shRNA significantly alleviated the miR
      143 inhibitor-induced high cell proliferation. Taken together, these results
      suggested that miR-143 acts as a tumor suppressor gene in HCC. The downregulation
      of mi-143 promoted cell proliferation by regulating PKCepsilon in the HCC cells.

PMID- 28765890
TI  - Fine particulate matter aggravates allergic airway inflammation through thymic
      stromal lymphopoietin activation in mice.
AB  - Fine particulate matter (PM2.5) has been linked to exacerbation of allergic
      airway inflammation in mice. However, the mechanism underlying exposure to PM2.5
      and subsequent and adverse effects remains to be fully elucidated. Therefore, the
      present study aimed to investigate the effects of PM2.5 by different levels on
      airway inflammation in mouse models of in allergic and steroid-resistant asthma.
      BALB/c mice were nasally instilled with PBS (control) or 10, 31.6 or 100 ug
      PM2.5, and randomly assigned into nine groups. The acute asthma model was
      previously induced to investigate the change of inflammatory cells in
      bronchoalveolar lavage fluid (BALF). Histopathological changes of the lung were
      assessed, in addition to levels of interleukin (IL)-4 and IL-13 in BALF and
      immunoglobulin Ein serum. Thymic stromal lymphopoietin (TSLP) proteinexpression
      levels were assessed by western blotting. The present study demonstrated that
      medium- and high-dose PM2.5 is linked to acute exacerbation of allergic airway
      inflammation in mice. In conclusion, the pathological mechanisms of PM2.5 may be
      associated with allergic/steroid-resistant airway inflammation, T-cell helper
      (Th)1/Th2 cytokine production and upregulation of TSLP expression in a murine
      model of allergic and steroid-resistant asthma.

PMID- 28765891
TI  - Non-coding RNA 886 promotes renal cell carcinoma growth and metastasis through
      the Janus kinase 2/signal transducer and activator of transcription 3 signaling
      pathway.
AB  - Non-coding RNA 886 (nc886) has been suggested to serve tumor-suppressing roles in
      several cancer cells. However, the expression pattern of nc886 and its function
      in renal cell carcinoma (RCC) has not been reported until now. The present study
      aimed to examine the expression of nc886 in human RCC tissues and to investigate
      the role of nc886 in RCC cell proliferation, apoptosis and invasion in vitro.
      Furthermore, whether nc886 exerts its function on RCC via Janus kinase 2/signal
      transducer and activator of transcription 3 (JAK2/STAT3) signaling was
      investigated. It was demonstrated that nc886 is overexpressed in human RCC
      tissues compared with normal tissues, as determined by reverse transcription
      quantitative polymerase chain reaction analysis. The nc886 mimic and inhibitor
      were transfected into the A-498 cells to overexpress or knock down nc886
      expression. Cell proliferation, cell apoptosis rate and cell invasion ability
      were determined by MTT, flow cytometry and Transwell-Matrigel invasion assays.
      The results demonstrated that nc886 overexpression promotes A-498 cell
      proliferation and invasion, and inhibits cell apoptosis, while nc886 knockdown
      resulted in the opposite effects. Furthermore, nc886 could activate the
      JAK2/STAT3 signaling pathway in A-498 cells. AG490, an inhibitor of JAK2, could
      attenuate the effects of nc886 on cell proliferation, apoptosis and invasion. In
      conclusion, to the best of our knowledge, the present study for the first time
      revealed the expression profile and the tumor-promoting role of nc886 in RCC.
      nc886 affects RCC cell proliferation, apoptosis and invasion at least partially
      via the activation of JAK2/STAT3 signaling. This study may provide a useful
      therapeutic target for RCC.

PMID- 28765892
TI  - Production of bFGF monoclonal antibody and its inhibition of metastasis in Lewis
      lung carcinoma.
AB  - Basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1
      (FGFR1) are associated with drug resistance in lung cancer. In the present study,
      mouse monoclonal antibodies (mAb) against human bFGF, targeting the binding site
      of bFGF with FGFR1 were produced, and the antitumor activity and inhibition of
      metastasis was studied in Lewis lung carcinoma (LLC). A total of four hybridoma
      cell strains that stably secreted bFGF mAb were obtained. mAbE12 was selected as
      the most effective for use in the following studies, with a relative affinity
      constant of 5.66x108 l/mol. mAbE12 was demonstrated to inhibit cell proliferation
      and tumor growth in vitro and in vivo. Furthermore, mAbE12 blocked migration and
      metastasis of LLC cells in vitro and in vivo. This occurred due to a mAbE12
      induced upregulation of E-cadherin expression through the protein kinase B
      glycogen synthase kinase 3 beta-Snail pathway. These results suggested that
      mAbE12 may be a potential antibody for the treatment of lung cancer.

PMID- 28765893
TI  - Endothelial semaphorin 7A promotes seawater aspiration-induced acute lung injury
      through plexin C1 and beta1 integrin.
AB  - Inflammation and edema are two main characteristics in seawater aspiration
      induced acute lung injury (ALI). In a previous study of the authors, it was
      demonstrated that endothelial semaphorin 7A (SEMA7A) serves an important role in
      the development of seawater-induced inflammation and edema. However, the
      mechanism of endothelial SEMA7A-mediated ALI remains unclear. Therefore, the
      authors explored the effect of SEMA7A in rat pulmonary microvascular endothelial
      cells (RPMVECs) and the interaction between endothelial SEMA7A and alveolar
      macrophages during seawater aspiration-induced ALI. The role of SEMA7A in
      endothelial permeability was detected using plexin C1 blocking antibody or SEMA7A
      small interfering (si)RNA. In addition, RPMVECs were co-cultured with rat
      alveolar macrophage cell line-NR8383 cells and pro-inflammatory cytokine
      production was detected. Interaction between the beta1 integrin and SEMA7A was
      detected using the beta1 integrin blocking antibody or SEMA7A siRNA. Seawater
      stimulation induced endothelial cytoskeleton remodeling, endothelial
      permeability, phosphorylation of cofilin, and increased the vascular endothelial
      growth factor (VEGF) expression in RPMVECs. Moreover, seawater stimulation led to
      expression of proinflammatory cytokines and activated the nuclear factor-kappaB
      pathway in co-cultured cells. However, blockage with the plexin C1 antibody
      inhibited endothelial cytoskeleton remodeling, endothelial permeability,
      phosphorylation of cofilin, and treatment with SEMA7A siRNA inhibited expression
      of VEGF in RPMVECs. In addition, blockage with beta1 integrin antibody reduced
      expression of proinflammatory cytokines and inhibited activation of NF-kappaB in
      co-culture cells. These results suggest that SEMA7A promotes seawater induced
      lung edema via plexin C1 and stimulates seawater induced lung inflammation via
      beta1 integrin.

PMID- 28765894
TI  - Follistatin-like protein 1 increases transepithelial resistance in kidney
      epithelial cells through Akt signaling.
AB  - Tight junctions are intercellular junctional structures that control paracellular
      permeability across epithelial cell sheets, and serve as a barrier to the
      intramembranic diffusion of components between apical and basolateral cell
      membrane domains. Follistatin-like protein 1 (FSTL1) has been reported to promote
      cellular metabolism and survival. FSTL1 has been revealed to be highly expressed
      in adult kidney tissues, and high FSTL1 levels have been reported in mouse and
      human serum samples; however, the roles of FSTL1 in the regulation of kidney
      function remain to be elucidated. In the present study, FSTL1 was demonstrated to
      increase the transepithelial electrical resistance in mouse inner medullary
      collecting duct (mIMCD3) cells. The molecular mechanisms underlying the effects
      of FSTL1 were also investigated and the results suggested that FSTL1 may exert
      its actions through the modulation of Akt signaling. In addition, FSTL1 was
      revealed to produce no effect on the migratory capabilities of mIMCD3 cells. The
      results of the present study suggested that FSTL1 may facilitate the formation of
      tight junctions and regulate their function in renal tubular epithelia.

PMID- 28765895
TI  - Oligomeric proanthocyanidins inhibit apoptosis of chondrocytes induced by
      interleukin-1beta.
AB  - Oligomeric proanthocyanidin (OPC) is a water-soluble plant polyphenolic compound
      known for its cytoprotective effects in various tissue types. However, its effect
      on chondrocytes has not been well characterized. The present study aimed to
      investigate the effect of OPC on interleukin-1beta (IL-1beta)-induced apoptosis
      in chondrocytes, and to determine the mechanisms underlying the protective
      effects of OPC. Knee articular chondrocytes obtained from 6-week-old SPF Kunming
      mice were cultured and serially passaged. First-generation chondrocytes were
      selected for subsequent experiments following toluidine blue staining. Subsequent
      to IL-1beta and OPC administration, an MTT assay was performed to examine the
      viability rate of chondrocytes, and the optimal drug concentration was
      determined. The fluorescence dye 2',7'-dichlorofluorescein diacetate was used to
      determine the intracellular content of reactive oxygen species (ROS).
      Mitochondrial membrane potential (MMP) was measured using a 5,5',6,6'-tetrachloro
      1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine iodide (JC-1) assay. The
      apoptosis rate of chondrocytes was assessed using an Annexin V-FITC/PI assay and
      ultrastructural changes were observed under an electron microscope. The results
      demonstrated that OPC increased the survival rate of chondrocytes against IL
      1beta-induced apoptosis. The most significant protective effect of OPC was
      observed at the concentration of 0.050 mg/ml. OPC reversed the increased ROS
      content and MMP levels, and inhibited IL-1beta-induced apoptosis in chondrocytes.
      In addition, OPC was revealed to protect the ultrastructural integrity of
      chondrocytes. Taken together, the results of the present study suggest that OPC
      protects chondrocytes against IL-1beta-induced damage by decreasing ROS content
      and MMP levels.

PMID- 28765896
TI  - 1,25(OH)2D3 treatment attenuates high glucose-induced peritoneal epithelial to
      mesenchymal transition in mice.
AB  - It has been previously demonstrated that 1,25(OH)2D3 prevents the progression of
      epithelial to mesenchymal transition (EMT). However, it remains unclear whether
      1,25(OH)2D3 has a role in peritoneal EMT stimulated by high glucose (HG)
      peritoneal dialysis fluid (PDF). The present study was performed to investigate
      the role of 1,25(OH)2D3 in the progression of EMT in the peritoneal mesothelium.
      A total of 35 male Kunming mice were randomly assigned into seven groups. In the
      control group, no diasylate or saline was infused. In the saline group, the mice
      were intraperitoneally injected with saline every day for 4 weeks. In the vitamin
      D group, the mice were subjected to intraperitoneal injections of 1 or 5 ug/kg of
      1,25(OH)2D3 once weekly (every Monday) for 4 weeks. The peritoneal dialysis (PD)
      group were intraperitoneally injected with a conventional 4.25% PDF daily for 4
      weeks. The vitamin D+PD group were intraperitoneally injected with 4.25% PDF
      daily and co-treated with 1 ug/kg or 5 ug/kg 1,25(OH)2D3 once weekly, for 4
      weeks. The peritoneal morphology and thickness were assessed by hematoxylin and
      eosin and Masson's trichrome staining. The peritoneal protein level of EMT
      markers (alpha-smooth muscle actin, fibronectin and E-cadherin), vitamin D
      receptor (VDR), B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein,
      transforming growth factor (TGF)-beta and Smad3 were evaluated by western blot
      analysis or immunohistochemical staining. Furthermore, apoptosis was assessed
      using a Caspase-3 activity assay. The results demonstrated that after 4 weeks of
      intraperitoneal injections in mice, HG-PDF decreased the expression of VDR,
      promoted EMT and apoptosis, and increased the thickness of the peritoneal
      membrane. However, 1,25(OH)2D3 treatment attenuated HG-induced EMT and apoptosis,
      and decreased peritoneal thickness, which may partially occur through inhibition
      of transforming growth factor TGF-beta/Smad pathways via 1,25(OH)2D3 binding to
      VDR. The present study demonstrated that 1,25(OH)2D3 attenuated HG-induced EMT
      and apoptosis in the peritoneal mesothelium through TGF-beta/Smad pathways.
      1,25(OH)2D3 treatment in conjunction with HG dialysate may provide an improved
      solution to the peritoneal injury in the process of PD.

PMID- 28765897
TI  - The Toll-like receptor 4 antagonist TAK-242 protects against chronic pancreatitis
      in rats.
AB  - Chronic pancreatitis is a progressive disease characterized by irreversible
      morphological changes to the pancreas, typically causing pain and permanent loss
      of function. It is a poorly understood disease with the pathogenesis remaining
      unclear. The authors' previous data demonstrated that the inhibition of Toll-like
      receptor 4 (TLR4) using TLR4 antagonist kinase (TAK)-242 attenuates taurocholate
      induced oxidative stress via the regulation of mitochondrial function in the
      pancreatic acinar cells of mice. In the present study, the effect of TAK-242 on
      trinitrobenzene sulfonic acid (TNBS)-induced chronic pancreatitis was
      investigated in rats. The results revealed that TAK-242 attenuated the severity
      of chronic pancreatic injury, and regulated extracellular matrix secretion and
      cellular immunity. In addition, TAK-242 treatment significantly decreased cell
      apoptosis, as evidenced by the reduction in Terminal deoxynucleotidyl transferase
      dUTP nick end labeling-positive cells in pancreas tissue sections, and also
      promoted cell proliferation in TNBS-treated animals. Furthermore, the results of
      the calibrated von Frey filament assay demonstrated that TAK-242 could prevent
      the pancreatitis-induced referred abdominal hypersensitivity. In summary, TAK-242
      exhibits protective effects against TNBS-induced chronic pancreatitis and may be
      a potential therapeutic strategy for the treatment of patients with chronic
      pancreatitis.

PMID- 28765898
TI  - Precise epitope determination of the anti-vimentin monoclonal antibody V9.
AB  - Vimentin is a type III intermediate filament protein that is typically expressed
      in mesenchymal cells. Overexpression of vimentin is frequently observed in
      several types of cancer and is often associated with epithelial-to-mesenchymal
      transition. It was recently reported that the serum vimentin level is
      significantly elevated in colon and liver tumors. Therefore, a more sensitive
      vimentin detection system may be useful for cancer screening and early detection.
      The V9 mouse monoclonal antibody (mAb), which recognizes the human vimentin
      protein, is widely used in routine pathology to identify mesenchymal cells using
      immunohistochemical analysis. Although it has been suggested that the epitope of
      the V9 mAb is located within the C-terminal region of vimentin, the precise amino
      acid sequence that it recognizes has not yet been identified. In the present
      study, we constructed several deletion mutants of the vimentin protein and
      examined their reactivity with the V9 mAb to accurately map its epitope. We
      confirmed that its epitope resides in the C-terminal region of vimentin, between
      amino acids 392-466. Additionally, cross-species comparison of amino acid
      sequence alignment of vimentin, as well as site-directed mutagenesis, revealed
      that one residue, the asparagine at position 417, is critical for antibody
      binding. Using smaller vimentin fragments ranging in length from 9 to 13
      residues, each containing this critical asparagine, we determined that the
      minimal residues required for V9 mAb recognition of human vimentin are the
      thirteen amino acid residues at positions 411-423 (411ISLPLPNFSSLNL423).

PMID- 28765899
TI  - Associations of adiponectin receptor 2 (AdipoR2) gene polymorphisms and AdipoR2
      protein expression levels with the risk of colorectal cancer: A case-control
      study.
AB  - The aim of the present study was to investigate the associations between
      adiponectin receptor 2 (AdipoR2) gene polymorphisms, AdipoR2 protein expression
      levels and the risk of colorectal cancer (CRC). From April 2012 to May 2015, 281
      CRC patients (case group) admitted to the China-Japan Friendship Hospital and 325
      healthy control subjects (control group) were recruited for the study. Peripheral
      venous blood samples were collected and the DNA was extracted. Genotyping was
      performed using denaturing high-performance liquid chromatography in the
      condition of partial degeneration. Linkage disequilibrium and haplotype were
      analyzed using SHEsis analysis software. AdipoR2 protein expression levels were
      detected by immunohistochemistry and logistic regression analysis was performed
      to determine the risk factors of CRC. The distribution of the TT genotype of
      AdipoR2 rs10773989 and the CC genotype of AdipoR2 rs1044471 was higher in the
      case group than in the control group (P<0.05). The AdipoR2 rs10773989
      polymorphism was associated with the degree of tumor infiltration in CRC (P<0.05)
      and the AdipoR2 rs1044471 polymorphism was associated with the degree of
      differentiation and Dukes' staging in CRC (P<0.05). The CT haplotype was
      identified as a protective factor, while the TC haplotype was a risk factor in a
      healthy population. AdipoR2 protein expression was associated with the degree of
      differentiation, Dukes' staging, degree of tumor infiltration and lymphatic
      metastasis in CRC (all P<0.05). Logistic regression analysis demonstrated that
      the TT genotype of AdipoR2 rs10773989 and CC genotype of AdipoR2 rs1044471 were
      independent risk factors for CRC. The AdipoR2 rs10773989 and rs1044471
      polymorphisms may be correlated with the susceptibility to CRC. In addition, the
      TC haplotype and AdipoR2 positive expression may increase the risk of CRC.

PMID- 28765900
TI  - miR-30a inhibits the biological function of breast cancer cells by targeting
      Notch1.
AB  - miR-30a is situated on chromosome 6q.13 and is produced by an intronic
      transcriptional unit. However, its role in regulating the apoptosis, invasion and
      metastasis of breast cancer cells is not yet fully understood. The aim of this
      study was to research the biological function of miR-30a and its direct target
      gene in breast cancer. The biological function of miR-30a was determined by
      examining breast cancer cell growth, apoptosis, metastasis and invasion. In
      addition, Notch1 expression was measured by western blot analysis, and a
      luciferase reporter vector was constructed to identify the miR-30a target gene.
      miR-30a was found to be significantly downregulated in breast cancer cells. We
      also found that miR-30a inhibited breast cancer cell viability, migration and
      invasion, and induced cell apoptosis. On the whole, our data indicate that miR
      30a attenuates the development of breast cancer by regulating the expression of
      the downstream target gene, Notch1.

PMID- 28765901
TI  - miR-127 contributes to ventilator-induced lung injury.
AB  - Although it is essential in critical care medicine, mechanical ventilation often
      results in ventilator-induced lung injury (VILI). Treating mice with
      lipopolysaccharide has been reported to upregulate the expression of miR-127,
      which has been implicated in the modulation of immune responses. However, the
      putative roles of miR-127 during the development of VILI have yet to be
      elucidated. The present study demonstrated that challenging mice with mechanical
      ventilation for 6 h significantly upregulated the expression of miR-127 in
      bronchoalveolar lavage fluid, serum and lung tissue samples. Conversely,
      following the downregulation of miR-127 expression in vivo using an adenovirus
      delivery system, VILI-associated pathologies, including alterations in the
      pulmonary wet/dry ratio, pulmonary permeability, lung neutrophil infiltration and
      levels of pro-inflammatory cytokines, were significantly attenuated. In addition,
      miR-127 knockdown inhibited the ventilation-induced activation of nuclear factor
      (NF)-kappaB and p38 mitogen-activated protein kinase (MAPK). These findings
      suggested that the upregulation of miR-127 expression may contribute to the
      development of VILI, through the modulation of pulmonary permeability, the
      induction of histopathological alterations, and the potentiation of inflammatory
      responses involving NF-kappaB and p38 MAPK-associated signaling pathways.

PMID- 28765902
TI  - Effects of microRNA-26b on proliferation and invasion of glioma cells and related
      mechanisms.
AB  - Neuroglioma is the most common primary malignant tumor in neurosurgery. Due to
      its short survival period and high patient mortality rate, neuroglioma is a major
      challenge in clinics. Elucidating the pathogenic mechanisms and associated
      molecular targets of neuroglioma can therefore benefit diagnosis and treatment of
      glioma. Previous studies have established the role of microRNA (miR)-26b in
      various tumors, including breast cancer, lymphoma and glioma. Its function and
      mechanism in neuroglioma, however, remains to be elucidated. In the present
      study, in vitro cultured U87 glioma cells were randomly divided into miR-26b
      mimic, miR-26b inhibitor and respective control (NC) groups. MTT assay was
      performed to detect the effect of miR-26b on cell proliferation, while a cell
      invasion assay detected its effects on cell invasion. Caspase-3 activity was also
      quantified to test cell apoptosis, followed by reverse transcription-quantitative
      polymerase chain reaction and western blotting to detect the variation of Bcl-2
      expression under the effect of miR-26b. miR-26b mimics transfection upregulated
      its expression in U87 cells, which had significantly reduced Bcl-2 mRNA and
      protein expression levels and higher casapse3 activity, and inhibited cell
      proliferation and invasion compared with the control group. The transfection of
      miR-26b inhibitor, in contrast, facilitated U87 cell proliferation and invasion,
      inhibited caspase-3 activity and elevated Bcl-2 mRNA/protein expression. In
      conclusion, miR-26 could facilitate apoptosis and inhibit proliferation/invasion
      of neuroglioma cells via downregulating Bcl-2 expression and potentiating caspase
      3 activity.

PMID- 28765903
TI  - Wild-type p53 controls the level of fibronectin expression in breast cancer
      cells.
AB  - Aberrant fibronectin (FN) expression is associated with poor prognosis, cell
      adhesion, and cell motility in a variety of cancer cells. In this study, we
      investigated the relationship between p53 and FN expression in breast cancer
      cells. Basal FN expression was significantly decreased by treatment with the p53
      activator III, RITA, in MCF7 breast cancer cells with wild-type p53. In addition,
      overexpression of wild-type p53 markedly decreased the level of FN expression in
      p53-mutant breast cancer cells. To examine the mechanism underlying the
      relationship between p53 and FN expression, we treated MCF7 breast cancer cells
      with the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). Our results
      showed that basal FN expression was increased by TPA treatment in a time
      dependent manner. In contrast, the level of p53 expression was decreased by TPA
      treatment. However, the expression of FN and p53 was not altered by TPA in p53
      mutant breast cancer cells. Furthermore, the alterations in FN and p53 expression
      in response to TPA were prevented by a specific MEK inhibitor, UO126. Finally, we
      demonstrated that TPA triggers degradation of p53 through the proteasomal pathway
      in MCF7 cells. TPA-induced FN expression was decreased by the proteasome
      inhibitor MG132. Under the same condition, p53 protein expression, but not mRNA
      expression, was reversed by MG132. Taken together, our data demonstrate that the
      level of FN expression is associated with the status and expression of p53 in
      breast cancer cells.

PMID- 28765904
TI  - Osthole protects against inflammation in a rat model of chronic kidney failure
      via suppression of nuclear factor-kappaB, transforming growth factor-beta1 and
      activation of phosphoinositide 3-kinase/protein kinase B/nuclear factor
      (erythroid-derived 2)-like 2 signaling.
AB  - Multiple pharmacological applications of osthole have been previously recognized,
      including antioxidant, anti-inflammatory, anti-platelet and estrogenic effects,
      and resistance to pain. The present study investigated the protective effects of
      osthole against inflammation in a rat model of chronic kidney failure (CRF) and
      the underlying mechanisms. Osthole treatment with significantly reversed CRF
      induced changes in serum creatinine, calcium, phosphorus and blood urea nitrogen
      levels in CRF rats. Male Sprague-Dawley rats (age, 8 weeks) received 200 mg/kg 2%
      adenine suspension to induce CRF in the model group. In the osthole-treated
      group, rats received 200 mg/kg 2% adenine suspension + osthole (40 mg/kg,
      intravenously). The results revealed that treatment with osthole significantly
      inhibited CRF-induced tumor necrosis factor-alpha, interleukin (IL)-8 and IL-6
      expression, and suppressed nuclear factor-kappaB (NF-kappaB) protein expression
      in CRF rats. Osthole treatment significantly attenuated the protein expression of
      transforming growth factor-beta1 (TGF-beta1), reduced monocyte chemoattractant
      protein-1 activity and increased the phosphoinositide 3-kinase (PI3K)/protein
      kinase B (Akt) ratio in CRF rats. These results suggested that osthole protects
      against inflammation in a rat model of CRF via suppression of NF-kappaB and TGF
      beta1, and activation of PI3K/Akt/nuclear factor (erythroid-derived 2)-like 2
      signaling. Therefore, osthole may represent a potential therapeutic agent for the
      treatment of CRF.

PMID- 28765905
TI  - miR-663 promotes NPC cell proliferation by directly targeting CDKN2A.
AB  - MicroRNAs (miRs) act as important regulators during the development and
      progression of human cancer; however, the regulatory mechanism of miR-663 in
      nasopharyngeal carcinoma (NPC) remains unclear. The present study demonstrated
      that serum miR-663 levels were significantly increased in patients with NPC
      compared with healthy controls. In addition, the serum levels of miR-663 were
      associated with the grade, lymph node metastasis and clinical stage of NPC. The
      expression of miR-663 was increased in NPC C666-1 cells, compared with normal
      nasopharyngeal epithelial NP69 cells. The knockdown of miR-663 markedly decreased
      the proliferation of C666-1 cells through the induction of cell cycle arrest at
      the G1 stage. Cyclin-dependent kinase inhibitor 2A (CDKN2A) was hypothesized to
      be a putative target of miR-663. Further investigation confirmed that miR-663 was
      able to directly bind to the 3' untranslated region of CDKN2A mRNA, and to
      negatively regulate CDKN2A protein expression in C666-1 cells. Inhibition of
      CDKN2A expression attenuated the suppressive effects of miR-663 knockdown on the
      proliferation and cell cycle progression of C666-1 cells. In addition, it was
      observed that the mRNA and protein levels of CDKN2A were decreased in C666-1
      cells compared with NP69 cells. In conclusion, the results of the present study
      demonstrated that miR-663 promoted the proliferation and cell cycle progression
      of NPC cells by directly targeting CDKN2A, suggesting that miR-663 may become a
      potential therapeutic target for the treatment of NPC.

PMID- 28765906
TI  - HPK1 positive expression associated with longer overall survival in patients with
      estrogen receptor-positive invasive ductal carcinoma-not otherwise specified.
AB  - Hematopoietic progenitor kinase 1 (HPK1) belongs to the mitogen activated protein
      kinase kinase kinase kinase (MAP4K) family of serine/threonine kinases, which
      have been associated with the incidence and progression of a variety of
      gastrointestinal malignant tumors in humans. However, the potential association
      between HPK1 expression and breast cancer, particularly invasive ductal carcinoma
      not otherwise specified (IDC-NOS) development, has not yet been examined. To
      address this gap, the present study aimed to evaluate HPK1 expression in IDC-NOS
      samples and to determine a relationship with clinical prognostic indicators, such
      as the expression levels of estrogen receptor (ER), progesterone receptor (PR)
      and human epidermal growth factor receptor 2 (HER2), as well as overall survival
      of the patients with IDC-NOS. HPK1 mRNA and protein expression in samples from
      148 patients with IDC-NOS were detected using immunohistochemistry, western
      blotting and reverse transcription-quantitative polymerase chain reaction. A
      total of 54 out of 148 (36.5%) samples were HPK1-positive, and 100 out of 148
      (67.6%) were ER-positive. Of the latter, 28% (28/100) were HPK1-positive, and a
      significant negative association of HPK1 expression with ER positivity was
      observed (P=0.002; r=-0.254). In addition, 43.2% (64/148) and 32.4% (48/100) of
      IDC-NOS tissues were PR- or HER2-positive, respectively; however, neither
      indicator correlated with HPK1 (P=0.109 and P=0.558, respectively). HPK1
      expression, axillary lymph node metastasis and tumor-node-metastasis (TNM) stage
      were identified as independent factors of overall survival (OS) in the ER
      positive group (P<0.05), and HPK1 positivity was associated with increased OS
      (P=0.048). HPK1 mRNA levels did not differ between IDC-NOS and normal adjacent
      breast tissues, whereas HPK1 protein levels were lower in IDC-NOS (P<0.05). These
      results suggested that HPK1 protein may be a potentially effective IDC-NOS
      therapeutic target.

PMID- 28765907
TI  - Antidepressant-like effects of Marasmius androsaceus metabolic exopolysaccharides
      on chronic unpredictable mild stress-induced rat model.
AB  - Marasmius androsaceus (M. androsaceus), a medicinal fungus, has various
      pharmacological activities including antidepression. The present study
      investigated the effects of exopolysaccharides obtained during M. androsaceus
      submerged fermentation in a chronic unpredictable mild stress (CUMS)-induced
      depression rat model. Similar to fluoxetine (positive drug), 4-week
      administration of M. androsaceus exopolysaccharides (MEPS) at doses of 6, 30 and
      150 mg/kg strongly enhanced bodyweight gain and sucrose consumption, and reduced
      the immobility time in forced swimming test and tail suspension test in CUMS
      rats. MEPS resulted in significant enhancement on the levels of noradrenalin,
      dopamine, 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid in the serum
      and hypothalamus of CUMS rats, as detected by ELISA. Western blotting results
      revealed that MEPS upregulated the protein expression levels of tyrosine
      hydroxylase in the hypothalamus of CUMS rats. In conclusion, these results
      confirmed the antidepressant-like effects of MEPS, and suggested that the
      monoamine neurotransmitter system is involved in its antidepressive effects in a
      CUMS rat model. The present study provided evidence for the clinical application
      of MEPS as an effective agent against depression.

PMID- 28765908
TI  - SERCA1 attenuates diaphragm relaxation and uptake rate of SERCA in rats with
      acute sepsis.
AB  - The present study aimed to investigate the effects of acute sepsis on diaphragm
      contractility and relaxation, via examining the Ca2+-uptake function of
      sarco/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA), and the
      protein levels of SERCA1, SERCA2 and the ryanodine receptor (RyR) of the
      sarcoplasmic reticulum (SR). A sepsis rat model was established through cecal
      ligation and puncture (CLP). A total of 6 and 12 h following CLP, the isometric
      contractile and relaxation parameters of the diaphragm were measured. In
      addition, Ca2+ uptake and release from the SR, and the protein expression levels
      of SERCA1, SERCA2 and RyR in diaphragm muscle tissue were investigated. At 6 and
      12 h post-CLP, the diaphragm half-relaxation time was prolonged and the maximum
      rate of tension decline was decreased and the Ca2+-uptake function of SERCA was
      markedly reduced. The maximum rate of twitch force development, the maximal
      twitch and tetanic tension, and the release function of SR were decreased at 12 h
      post-CLP. A total of 12 h following CLP, the protein expression levels of SERCA1
      were significantly downregulated, and its activity was significantly reduced;
      conversely, the protein levels of SERCA2 remained unaltered. The present findings
      indicated that at the acute stage of sepsis induced by CLP the contractile and
      relaxation functions of the diaphragm were significantly compromised. The
      impairments in relaxation may be a result of the impaired uptake function of the
      SR and the downregulation in SERCA1 protein expression. Conversely, the
      compromised contractility may be a result of the impaired release function of the
      SR and the downregulation in RyR protein levels. This could provide some new
      insights into the treatment of sepsis. In acute stages of sepsis, the improvement
      of SERCA function could reduce the disequilibrium of calcium homeostasis to
      improve the critical illness myopathy and respiratory failure.

PMID- 28765909
TI  - Attenuation of MUC4 potentiates the anticancer activity of auranofin via
      regulation of the Her2/Akt/FOXO3 pathway in ovarian cancer cells.
AB  - Previously, we reported that auranofin induces apoptosis in SKOV3 cells via
      regulation of the IKKbeta/FOXO3 pathway. In the present study, we reveal that the
      anticancer activity of auranofin in SKOV3 cells could be enhanced by the
      attenuation of MUC4 through the regulation of the Her2/Akt/FOXO3 pathway.
      Compared to the control-siRNA, siRNA transfection against MUC4 into SKOV3 cells
      accelerated the protein degradation of Her2. Under the same conditions, the
      expression level of phosphorylated Akt was also downregulated leading to an
      increase of FOXO3 in the nucleus. Notably, auranofin treatment in SKOV3 cells
      also resulted in the downregulation of the expression levels of both Her2 and
      phosphorylated Akt. Thus, Her2 was identified as the common molecular target
      protein by siRNA transfection against MUC4. Western blot analysis of total and
      nuclear fraction lysates from SKOV3 cells revealed that attenuation of MUC4
      combined with auranofin treatment in SKOV3 cells synergistically activated FOXO3
      translocation from the cytoplasm to the nucleus through the regulation of the
      Her2/Akt/FOXO3 pathway. Attenuation of MUC4 by siRNA transfection potentiated the
      antitumor effect of auranofin which was examined by performing in vitro assays
      such as WST-1, cell counting, colony formation, TUNEL and Annexin V staining. In
      addition, western blot analysis of the apoptosis-related proteins such as PARP1,
      caspase-3, Bim extra large (EL), Bax and Bcl2 revealed that the attenuation of
      MUC4 by siRNA transfection potentiates the pro-apoptotic activity of auranofin in
      SKOV3 cells. Collectively, auranofin could regulate the Her2/Akt/FOXO3 signaling
      pathway in SKOV3 cells and be used as a potential antitumor agent considering the
      expression of MUC4 in ovarian cancer patients.

PMID- 28765910
TI  - EVI5 is a novel independent prognostic predictor in hepatocellular carcinoma
      after radical hepatectomy.
AB  - The present study explored the correlation of ecotropic viral integration site 5
      (EVI5) expression with clinicopathological features and prognosis in
      hepatocellular carcinoma (HCC). A total of 205 HCC patients were included
      retrospectively. Quantitative real-time polymerase chain reaction (RT-qPCR) and
      western blotting were performed to detect the profile of EVI5 expression in HCC
      cell lines and fresh tissues. Archived paraffin-embedded specimens were
      investigated for EVI5 expression by immunohistochemistry (IHC). Both the mRNA and
      protein levels of EVI5 were obviously upregulated in HCC cell lines and tumor
      tissues. EVI5 protein level was closely associated with the clinicopathological
      characteristics, including liver function (P=0.013), venous invasion (P=0.015)
      and TNM stage (P=0.014). Furthermore, univariate analysis showed that the
      patients with high EVI5 expression indicated shorter overall survival (OS,
      P<0.001) and recurrence-free survival (RFS, P=0.001) than those with low EVI5
      expression. Importantly, high EVI5 expression also exerts predictive power for
      higher postoperative recurrence rate by stratified analysis. Multivariate Cox
      regression analysis demonstrated that OS was correlated with both tumor number
      (P=0.046) and EVI5 expression (P<0.001) and that RFS was correlated with serum
      AFP (P=0.023), tumor number (P=0.036) and EVI5 expression (P<0.001). Taken
      together, EVI5 is an useful independent prognostic marker of survival and
      recurrence in hepatocellular carcinoma.

PMID- 28765911
TI  - LCMR1 interacts with DEK to suppress apoptosis in lung cancer cells.
AB  - To win the war against lung cancer, the molecular mechanisms underlying its
      oncogenesis and metastasis must be identified in order to develop novel diagnosis
      and treatment strategies. We previously identified a novel gene, namely lung
      cancer metastasis related protein 1 (LCMR1; GenBank accession no. AY148462),
      which was demonstrated to be overexpressed in non-small-cell lung cancer. LCMR1
      expression was significantly associated with clinical stage. To further
      understand the mechanism of LCMR1 in lung cancer, the present study screened a
      cDNA library from the lung cancer cell line 95D for proteins interacting with
      LCMR1 by yeast two-hybrid assay, and the protein DEK was identified. Co
      immunoprecipitation and glutathione S-transferase pull-down assays were performed
      to confirm the interaction between LCMR1 and DEK in vivo and in vitro. The
      results demonstrated that the interaction was mediated primarily by the N
      terminal region of DEK, suggesting that LCMR1 may be involved in the regulation
      of cell apoptosis. Using RNA interference, DEK and LCMR1 were demonstrated to
      cooperate in the inhibition of apoptosis in lung cancer cells, and this effect
      was associated with the induced myeloid leukemia protein cell differentiation
      protein 1 pathway. The present findings suggest that LCMR1 might serve as a
      potential molecular target for lung cancer therapy.

PMID- 28765912
TI  - Disorder of the mevalonate pathway inhibits calcium-induced differentiation of
      keratinocytes.
AB  - Mutation of genes encoding the enzymes of the mevalonate pathway cause a variety
      of diseases, including skin disorders. Mutation of four genes in this pathway,
      including mevalonate kinase, phosphomevalonate kinase, mevalonate diphosphate
      decarboxylase and farnesyl diphosphate synthase, have demonstrated to be
      responsible for porokeratosis (PK). However, the pathogenesis of PK remains
      unclear. In the present study, specific enzyme inhibitors of the mevalonate
      pathway, including pravastatin (PRA), alendronate (ALD), farnesyl transferase
      inhibitor (FTI-277) and geranylgeranyl transferase inhibitor (GGTI-298), were
      used to investigate the effect on differentiation of keratinocytes (KCs). Western
      blotting demonstrated that PRA, ALD, FTI-277 or GGTI-298 alone, or in
      combination, inhibited the expression level of calcium-induced differentiation
      maker involucrin (INV) in KCs. ALD and PRA induced greater inhibition of INV
      compared with FTI-277 and GGTI-298 treatment. These inhibitors additionally
      influenced the expression levels of keratin1. Mechanistic studies revealed that
      treatment of cells with inhibitors decreased the expression levels of p53 and
      Notch1, and regulated activation of the mitogen activated protein kinase and
      phosphoinositide-3-kinase/protein kinase B signaling pathways. The results of the
      present study suggested that regulation of the mevalonate pathway may be
      necessary for differentiation of KCs, and the pathogenesis of disseminated
      superficial actinic PK.

PMID- 28765913
TI  - Danshensu attenuates aldosterone-induced cardiomyocytes injury through
      interfering p53 pathway.
AB  - Heart failure, characterized by impaired systolic and/or diastolic function, is a
      common cardiovascular disease. The loss of cardiomyocytes due to various factors,
      including through necrosis or apoptosis can result in heart failure. Previous
      studies have indicated that excessive aldosterone (ALD) serves an essential role
      in the process of heart failure, and the heart is also one of the direct targets
      of ALD, which can provoke hypertrophy and the apoptosis of cardiomyocytes. The
      aim of the present study was to investigate the protective effect of danshensu
      (DSS) on ALD-induced cardiomyocytes injury. The present results demonstrated that
      DSS increased cell viability and decreased the leakage of lactate dehydrogenase
      in cardiomyocytes exposed to ALD. In addition, DSS decreased the apoptotic rate
      of ALD-stimulated cells. Further research indicated that DSS- and cellular tumor
      antigen p53 (p53)-alone or combination treatment was able to decrease the
      expression levels of apoptosis regulator BAX and caspase-3, and increase the
      expression of apoptosis regulator B-cell lymphoma (Bcl)-2 in ALD-stimulated
      cardiomyocytes. Taken together, the results of the present study suggest that DSS
      inhibits the harmful effects of ALD on cardiomyocytes via interfering with the
      p53 signaling pathway. These results provide novel evidence for the potential
      protective effects of DSS.

PMID- 28765914
TI  - Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the
      geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells.
AB  - Numerous clinical studies have reported that statins increase the plasma
      concentration of arachidonic acid, which is an omega-6 long-chain polyunsaturated
      fatty acid (LCPUFA), and decrease the concentrations of eicosapentaenoic acid and
      docosahexaenoic acid, which are omega-3 LCPUFAs. These findings indicate that
      statins may affect the endogenous synthesis of LCPUFAs, which is regulated by
      fatty acid desaturases (FADSs) and elongation of very long-chain fatty acids
      proteins (ELOVLs). The present study aimed to investigate the roles of the
      intrinsic mevalonate cascade and Rho-dependent pathway in statin-induced
      regulation of these desaturases and elongases, as well as cell viability using
      mouse 3T3-L1 cells. mRNA expression was analyzed by quantitative polymerase chain
      reaction. Treatment with atorvastatin decreased cell viability and increased the
      mRNA expression levels of Fads1, Fads2 and ELOVL fatty acid elongase 5 (Elovl5)
      in a dose-dependent manner. Mevalonate and geranylgeranyl pyrophosphate (GGPP),
      but not cholesterol, fully reversed the atorvastatin-induced downregulation of
      cell viability and upregulation of gene expression; however, mevalonate itself
      did not affect cell viability and gene expression. The Rho-associated protein
      kinase inhibitor Y-27632 inhibited the mevalonate- and GGPP-mediated reversal of
      atorvastatin-induced upregulation of Fads1, Fads2 and Elovl5. These findings
      indicated that statins may affect the endogenous synthesis of LCPUFAs by
      regulating Fads1, Fads2 and Elovl5 gene expression via the GGPP-dependent Rho
      kinase pathway in mouse 3T3-L1 cells.

PMID- 28765915
TI  - miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast
      cancer.
AB  - It is not well established whether miR-93 is involved in drug resistance and
      epithelial-mesenchymal transition (EMT) in breast cancer, and its underlying
      mechanism remains uncertain. In the present study, the expression differences of
      miR-93 between paired breast cancer tissues confirmed it is involved in the
      progression of breast cancer. Such a difference was also observed in doxorubicin
      resistant and -sensitive cells. Overexpressed miR-93 in sensitive cells revealed
      increases in cellular proliferation and the expression levels of drug-resistant
      related genes, and a decrease in sensitivity to doxorubicin. This demonstrated
      the relationship between miR-93 and breast cancer drug resistance.
      Simultaneously, EMT was confirmed in miR-93 overexpressing sensitive cells. This
      indicated the triadic relationship among miR-93, EMT and drug resistance in
      breast cancer. We applied the Dual-luciferase Reporter assay to expose the direct
      interaction between miR-93 and PTEN, which suggested that miR-93 contributes to
      inducing EMT and drug resistance of breast cancer cells by targeting PTEN.

PMID- 28765916
TI  - Low co-expression of epidermal growth factor receptor and its chaperone heat
      shock protein 90 is associated with worse prognosis in primary glioblastoma, IDH
      wild-type.
AB  - Epidermal growth factor receptor (EGFR) is a major oncogenic driver in
      glioblastoma (GBM) without mutations in the isocitrate dehydrogenase gene (IDH
      wildtype). Heat shock protein 90 (HSP90) is a regulator of the stability of
      oncogenic proteins including EGFR, thereby acting as a molecular chaperone. We
      investigated the expression of EGFR and its chaperone HSP90 in GBM, IDH-wildtype.
      Tissue availability permitted analysis of 237/449 consecutive GBM cases, among
      them 214 IDH-wildtype (90.3%). The expression of EGFR and HSP90 was analysed by
      immunohistochemistry on a tissue microarray containing various tumour regions.
      The expression intensity (EI), and an expression score (ES) combining the
      percentage of stained cells with EI were determined for both markers. Overall,
      there was a positive correlation between EGFR and HSP90 expression (EI; r=0.275,
      P<0.001; ES, r=0.333, P<0.001). The expression of EGFR and HSP90 was
      significantly higher in the tumour centre, compared to the infiltration front
      (EI, P=0.002; ES, P<0.001). Survival data were available in 96 IDH-wildtype
      cases, and high expression of EGFR (ES only) was in trend associated with better
      outcome, but failed to meet statyistical significance (P=0.061). A combination of
      EGFR and HSP90, however, discriminated between different prognostic groups, with
      EGFRlow/HSP90low tumours showing the worst prognosis in univariate analysis
      (P=0.001), and in multivariate analysis including the other relevant prognostic
      factors age, MGMT status and postoperative treatment [n=76; hazard ratio
      (HR)=0.571; 95% confidence interval (CI) 0.328-0.996; P=0.048]. EGFR expression
      stratified most pronounced among HSP90low tumours, where the EGFRhigh phenotype
      was associated with longer survival. Our results reveal a variable reliance on
      the signalling pathway by EGFR in GBM, IDH-wildtype. Low co-expression was
      associated with worse prognosis.

PMID- 28765917
TI  - Inhibition of the growth of hepatocellular carcinoma cells through fibroblast
      growth factor 18 suppressed by miR-139.
AB  - Hepatocellular carcinoma (HCC) is a highly malignant tumor and one of the most
      common causes for human cancer-related deaths. Fibroblast growth factor 18
      (FGF18) is overexpressed in many types of cancer, and is associated with cell
      proliferation, invasion and angiogenesis. miR-139 has recently been reported as a
      tumor suppressor in various types of cancer and it can regulate many tumor
      related genes, however its association with FGF18 expression in HCC has not been
      reported and thus remains unknown. In the present study, to explore the potential
      regulation mechanism of miR-139 with FGF18 in HCC, HCC tissues and cell lines
      were used. The results revealed that FGF18 was highly expressed in HCC tissues
      and cells, however miR-139 was lowly expressed. FGF18 was demonstrated to be a
      direct target of miR-139. Furthermore, the suppressive effect of miR-139 on FGF18
      and in turn on proliferation, apoptosis, invasion, migration and tumor-induced
      angiogenesis of HCC cells was investigated. FGF18 was suggested as a prognostic
      biomarker and therapeutic target in HCC patients and miR-139 may be a promising
      strategy used in HCC treatment via the suppression of FGF18.

PMID- 28765918
TI  - TcpC secreting uropathogenic E. coli promoted kidney cells to secrete MIP-2 via
      p38 MAPK pathway.
AB  - Pyelonephritis is an infection of the upper urinary tract with characteristic
      histological change to neutrophil infiltration in the kidney. The majority of
      pyelonephritis is caused by uropathogenic Escherichia (E.) coli (UPEC) bearing
      distinct virulence factors. Toll/interleukin-1 receptor domain-containing protein
      C (TcpC) encoded by E. coli is an important virulence factor in the majority of
      strains of UPEC and inhibits macrophage-mediated innate immunity, which serves an
      essential role in the pathogenesis of pyelonephritis. In the present study, it
      was demonstrated that TcpC induced kidney cells to produce macrophage
      inflammatory protein-2 (MIP-2; also known as C-X-C motif chemokine 2). MIP-2
      concentration in kidney homogenates from TcpC-secreting UPEC CFT073 (TcpCwt)
      murine pyelonephritis models was significantly higher compared with that in
      kidney homogenates from tcpC knockout CFT073 (TcpC-/-) models. In vitro, TcpCwt
      dose-dependently promoted MIP-2 secretion in HEK-293 cells. The concentration of
      MIP-2 in culture supernatants of HEK-293 co-cultured with TcpCwt was profoundly
      higher compared with that of HEK-293 co-cultured with TcpC-/-. In the presence of
      anti-TcpC antibody, the enhancement effect of TcpCwt on MIP-2 production was
      completely abrogated, suggesting that the enhanced production of MIP-2 was
      mediated by secreted TcpC. Furthermore, it was demonstrated that TcpC-/-
      treatment had no effect on the p38 mitogen activated protein kinase (MAPK)
      signaling pathway, while TcpCwt treatment resulted in the activation of p38 MAPK
      in HEK-293 cells, as indicated by a simultaneous increase in p38 and
      phosphorylated-p38. In addition, inhibition of p38 MAPK with SB203580
      significantly decreased MIP-2 concentration and neutrophil recruitment activity
      in the supernatants of HEK-293 cells co-cultured with TcpCwt. This indicates that
      TcpC may promote MIP-2 production in kidney cells through the p38 MAPK signaling
      pathway. Taken together, the data of the present study demonstrated that TcpC can
      induce MIP-2 production, which may contribute to the characteristic histological
      change associated with pyelonephritis. This data has provided novel evidence to
      further clarify the pathogenesis of pyelonephritis and novel directions on the
      pathogenicity of TcpC-secreting UPEC.

PMID- 28765919
TI  - Age at menopause and hormone replacement therapy as risk factors for head and
      neck and oesophageal cancer (Review).
AB  - There were ~986,000 cases of head and neck cancer (HNC) and oesophageal cancer
      diagnosed worldwide in 2012. The incidence of these types of cancer is much
      higher in males than females, although this disparity decreases in the elderly
      population, suggesting a role for hormones as a risk factor. This systematic
      review investigates the potential role of female hormones [age at menopause and
      use of hormone replacement therapy (HRT)] as risk factors for HNC/oesophageal
      squamous cell carcinoma (SCC). The electronic databases MEDLINE, Web of Science,
      EMBASE and Cochrane were searched. Only studies with at least 50 cases of
      HNC/oesophageal SCC, with data on age at menopause, smoking, alcohol, age and
      socioeconomic status or educational attainment, were included. The Newcastle
      Ottawa Scale was used for assessing risk of bias. Eight studies met the inclusion
      criteria (5 oesophageal SCC, 2 HNC and 1 combined oesophageal SCC and HNC). HRT
      was shown to reduce the risk of HNC (HR, 0.78; 95% CI, 0.61-0.99) in one study.
      Our results showed that earlier age at menopause is a risk factor for oesophageal
      SCC, with women entering menopause at <45 years having double the risk of those
      entering menopause at age >50 years. Similar, but less striking, results were
      observed for HNC. HRT was found to reduce the risk of HNC/oesophageal SCC, but
      the evidence is inconclusive. We, therefore, recommend that consideration should
      be given to collecting data on reproductive factors and exposure to HRT, as
      routine practice, in future epidemiological and clinical studies of these
      cancers. The concept of oestrogen deficiency as a risk for HNC/oesophageal SCC
      deserves further exploration in future laboratory and clinical studies.

PMID- 28765920
TI  - MicroRNA-635 inhibits the malignancy of osteosarcoma by inducing apoptosis.
AB  - Recent evidence has suggested that microRNAs (miRs), which are a class of non
      coding RNAs, serve diverse roles in tumorigenesis. However, the role of miR-635
      in osteosarcoma (OS) remains unknown. The present study revealed that miR-635 may
      be a tumor suppressive miR. The expression of miR-635 was significantly decreased
      in OS specimens. In addition, the proliferation and invasion of OS cells
      transfected with miR-635 may be effectively attenuated. Transfection of cells
      with miR-635 may further inhibit tumor growth in vivo. miR-635 may antagonize
      tumorigenesis of OS possibly by inducing apoptosis, as demonstrated by flow
      cytometric analysis and caspase-3 kinase assays. The data of the present study
      suggested that miR-635 may be a novel tumor suppressor and may serve as a
      putative diagnostic marker for patients with OS.

PMID- 28765921
TI  - miR-198-induced upregulation of Livin may be associated with the prognosis and
      contribute to the oncogenesis of lung adenocarcinoma.
AB  - Livin, a member of the inhibitor of apoptosis protein (IAP) family, is expressed
      at a high level in lung adenocarcinoma and influences the progression of cancer,
      and its response to chemotherapy and radiotherapy. Aberrant microRNA (miRNA)
      expression has also been associated with cancer initiation and development.
      However, the clinical significance of Livin and its relationship with miRNAs in
      lung adenocarcinoma are still unclear. In the present study, the expression level
      of Livin in 90 pairs of lung adenocarcinoma and their adjacent tissues were
      detected by immunohistochemistry staining. Spearman correlation and Kaplan-Meier,
      univariate and multivariate analyses were applied to evaluate the correlation
      between the expression of Livin and clinical characteristics. With the
      integration of bioinformatics analysis and dual-luciferase reporter gene assays,
      we identified the miRNA that can target Livin mRNA. The functional effects of
      miRNA-mediated Livin knockdown were assessed by Cell Counting Kit-8 (CCK-8) and
      apoptosis assays, and cell cycle analysis. The present study revealed that Livin
      was upregulated in lung adenocarcinoma tissues and may be associated with the
      poor prognosis in lung adenocarcinoma patients. The overexpression of Livin is
      partly caused by the downregulation of miR-198. Further exploration revealed that
      miRNA-198-mediated silencing of Livin significantly inhibited cell growth and
      enhanced apoptosis of A549 cells, accompanied by marked upregulation of caspase
      3. Finally, we observed that the miR-198 overexpression and Livin neutralization
      had similar effects on improving cisplatin chemosensitivity in A549 cells.
      Overall, these findings suggest that Livin has the potential to become a
      biomarker for predicting the prognosis of lung adenocarcinoma and may provide a
      promising strategy for assisting chemotherapy of lung adenocarcinoma through the
      miR-198/Livin/caspase-3 regulatory network.

PMID- 28765922
TI  - Electric field exposure promotes epithelial-mesenchymal transition in human lens
      epithelial cells via integrin beta1-FAK signaling.
AB  - Electric field (EF) exposure can affect the elongation, migration, orientation,
      and division of cells. The present study tested the hypothesis that EF may also
      affect epithelial-mesenchymal transition (EMT) in lens epithelial cells and that
      this effect may be an important inducer in the pathological process of posterior
      capsule opacification (PCO). Human lens epithelial (HLE)-B3 cells were exposed to
      an EF. Experiments were performed in the presence or absence of an anti-integrin
      beta1 blocking antibody or a small molecule inhibitor targeting focal adhesion
      kinase (FAK). Cell morphology changes were observed by microscopy. The expression
      levels of integrin beta1, FAK, phosphorylated (p)FAK and of EMT markers, E
      cadherin and Vimentin, were examined by immunofluorescence, reverse transcription
      quantitative polymerase chain reaction and western blotting. Following exposure
      to EF, HLE-B3 cells appeared elongated and resembled more fibroblast-like cells.
      Expression of E-cadherin was decreased, while expression of Vimentin was
      increased in HLE-B3 cells exposed to EF, compared with control cells. In
      addition, the mRNA expression levels of integrin beta1 were increased, and the
      protein expression levels of integrin beta1 and pFAK were increased in HLE-B3
      cells exposed to EF, compared with control cells. Blocking of integrin beta1
      suppressed the EMT-related morphological changes of HLE-B3 cells and reduced the
      activation of FAK following EF exposure. However, blocking of pFAK did not affect
      the EMT status of HLE-B3 cells induced by EF. In conclusion, the present study
      demonstrated that EF exposure induced EMT in HLE-B3 cells and that this effect
      may partially be mediated by the activation of integrin beta1-FAK signaling. The
      present results may provide a new mechanistic approach to prevent the development
      of PCO.

PMID- 28765923
TI  - Bombyx mori hemocyte extract has anti-inflammatory effects on human phorbol
      myristate acetate-differentiated THP-1 cells via TLR4-mediated suppression of the
      NF-kappaB signaling pathway.
AB  - Hemolymph is the circulating fluid of insects and is a key component of their
      immune system. However, little is known concerning hemocyte identification,
      development, differentiation and related cellular immune responses. The present
      study aimed to determine whether a hemocyte extract prepared from Bombyx mori
      larvae had anti-inflammatory effects; THP-1 (a human monocytic leukemia cell
      line) cells that had been differentiated into macrophage-like cells by treatment
      with phorbol myristate acetate (PMA) were used. THP-1 cells were cultured with
      different concentrations of a B. mori hemocyte extract prior to exposure to
      lipopolysaccharide (LPS) to induce an inflammatory response. The effects of the
      B. mori hemocyte extract on anti-inflammatory pathways were determined using
      reverse transcription-quantitative polymerase chain reaction and western blotting
      to assess the expression of pro-inflammatory molecules. The B. mori hemocyte
      extract inhibited the LPS-induced mRNA expression of Toll-like receptor 4 in
      addition to LPS-induced interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis
      factor-alpha. Treatment of PMA-differentiated THP-1 cells with B. mori hemocyte
      extract also inhibited inducible nitric oxide synthase and cyclooxygenase-2
      transcription and translation. Nuclear factor-kappaB activation and
      phosphorylation also decreased. Further in-depth functional studies are required
      to understand the mechanism underlying the anti-inflammatory effects of silkworm
      hemocyte extract.

PMID- 28765924
TI  - MRI reveals slow clearance of dead cell transplants in mouse forelimb muscles.
AB  - A small molecule tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA)4-TPP
      agent is used to label human mesenchymal stem cells (hMSCs) via electroporation
      (EP). The present study assessed the cytotoxicity of cell labeling, in addition
      to its effect on cell differentiation potential. There were no significant
      adverse effects on cell viability or differentiation induced by either EP or
      cellular uptake of (Gd-DOTA)4-TPP. Labeled live and dead hMSCs were transplanted
      into mouse forelimb muscles. T2-weighted magnetic resonance imaging (MRI) was
      used to track the in vivo fate of the cell transplants. The labeling and imaging
      strategy allowed long term tracking of the cell transplants and unambiguous
      distinguishing of the cell transplants from their surrounding tissues. Cell
      migration was observed for live hMSCs injected into subcutaneous tissues, however
      not for either live or dead hMSCS injected into limb muscles. A slow clearance
      process occurred of the dead cell transplants in the limb muscular tissue. The
      MRI results therefore reveal that the fate and physiological activities of cell
      transplants depend on the nature of their host tissue.

PMID- 28765925
TI  - Altered expression of microRNA-98 in IL-1beta-induced cartilage degradation and
      its role in chondrocyte apoptosis.
AB  - Osteoarthritis (OA) is a multifactorial disease characterized by degeneration of
      the articular cartilage due to genetic and epigenetic components. The
      pathogenesis of OA is complex and the mechanism of chondrocyte homeostatic
      regulation remains to be fully elucidated. Previous studies have demonstrated
      that microRNAs (miRNAs/miR) contribute to cartilage dysfunction. However, the
      functional role of miR-98 in interleukin-1beta (IL-1beta)-induced chondrocyte
      apoptosis in OA cartilage remains to be investigated. The present study aimed to
      identify and characterize the expression profile of miR-98 and apoptosis
      associated proteins in healthy and OA chondrocytes, and western blot analysis and
      TUNEL staining were used to evaluate the role of miR-98 in the regulation of
      chondrocyte apoptosis. The present study demonstrated that miR-98 expression was
      increased in OA chondrocytes in response to IL-1beta stimulation, and the
      expression levels of apoptosis-associated proteins, including Fas cell surface
      death receptor, caspase-3, caspase-8 and B-cell lymphoma-2 (Bcl-2)-associated X
      protein, were also increased in IL-1beta-stimulated chondrocytes. In addition, it
      was revealed that upregulation of miR-98 was accompanied by reduced expression of
      Bcl-2 following exposure to IL-1beta. IL-1beta-induced downregulation of Bcl-2
      was associated with miR-98-mediated translational repression. Transfection of OA
      chondrocytes with a miR-98 inhibitor had an inhibitory effect on IL-1beta-induced
      cell apoptosis, increased cell proliferation and upregulated Bcl-2 expression. It
      is possible that miR-98 inhibited IL-1beta-induced chondrocyte apoptosis by
      modulating Bcl-2 expression levels. The findings of the present study indicated
      that the effects of miR-98 on chondrocyte apoptosis were induced by regulation of
      Bcl-2 expression. In addition, the present study confirmed that miR-98 targeted
      the 3'-untranslated region of Bcl-2. In conclusion, miRNA-coordinated regulation
      of apoptosis-associated protein expression has been identified in OA chondrocytes
      following IL-1beta induction.

PMID- 28765926
TI  - Imaging characteristics of adult onset Still's disease demonstrated with 18F-FDG
      PET/CT.
AB  - The diagnosis of adult onset Still's disease (AOSD) is non-specific, and requires
      the exclusion of other diseases including infectious, inflammatory and malignant
      diseases. The current study aimed to summarize the imaging characteristics of
      fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computerized
      tomography (CT) in patients with AOSD. The 18F-FDG PET/CT characteristic
      observations of 32 patients with definite AOSD were retrospectively reviewed
      based on visual interpretation and the semi-quantitative index of standard uptake
      value of maximum (SUVmax). Among 32 patients, no normal case was observed.
      Abnormal FDG accumulation by the spleen, bone marrow and lymph nodes was the main
      observation of the PET/CT images. Totals of 27 (84.4%) and 26 cases (81.3%) were
      identified with diffusely elevated FDG uptake by the spleen and bone marrow,
      respectively, and the average SUVmax was 4.2+/-1.1 and 4.6+/-0.6, respectively. A
      total of 20 cases (62.5%) showed lymphadenopathy with FDG uptake, with the range
      of SUVmax from 2.2-13.9. In addition, 7 patients (21.9%) were observed to exhibit
      effusion without FDG uptake, 1 case presented with abnormal FDG uptake by the
      skin, and another by the right shoulder joint. In addition, no abnormally
      elevated FDG uptake by the liver or large vessels was observed. Due to non
      specific imaging features, 18F-FDG PET/CT could not be directly helpful in
      diagnosing AOSD. However, 18F-FDG PET/CT serves important roles in evaluating the
      involved extent of AOSD, and guiding the biopsy of lymph nodes, bone marrow or
      other tissues, which may aid in the development of novel clinical management
      strategies.

PMID- 28765927
TI  - A decrease in ubiquitination and resulting prolonged life-span of KIT underlies
      the KIT overexpression-mediated imatinib resistance of KIT mutation-driven canine
      mast cell tumor cells.
AB  - Overexpression of KIT is one of the mechanisms that contributes to imatinib
      resistance in KIT mutation-driven tumors. Here, the mechanism underlying this
      overexpression of KIT was investigated using an imatinib-sensitive canine mast
      cell tumor (MCT) line CoMS, which has an activating mutation in KIT exon 11. A
      KIT-overexpressing imatinib-resistant subline, rCoMS1, was generated from CoMS
      cells by their continuous exposure to increasing concentrations of imatinib.
      Neither a secondary mutation nor upregulated transcription of KIT was detected in
      rCoMS1 cells. A decrease in KIT ubiquitination, a prolonged KIT life-span, and
      KIT overexpression were found in rCoMS1 cells. These events were suppressed by
      withdrawal of imatinib and were re-induced by re-treatment with imatinib. These
      findings suggest that imatinib elicited overexpression of KIT via suppression of
      its ubiquitination. These results also indicated that imatinib-induced
      overexpression of KIT in rCoMS1 cells was not a permanently acquired feature but
      was a reversible response of the cells. Moreover, the pan deubiquitinating enzyme
      inhibitor PR619 prevented imatinib induction of KIT overexpression, suggesting
      that the imatinib-induced decrease in KIT ubiquitination could be mediated by
      upregulation and/or activation of deubiquitinating enzyme(s). It may be possible
      that a similar mechanism of KIT overexpression underlies the acquisition of
      imatinib resistance in some human tumors that are driven by KIT mutation.

PMID- 28765928
TI  - Metabolic characteristics of Rhizoma Coptidis intervention in spontaneously
      hypertensive rats: Insights gained from metabolomics analysis of serum.
AB  - The present study aimed to investigate the intervention mechanisms of Rhizoma
      Coptidis using spontaneously hypertensive rats. A serum metabolomics analysis was
      performed with high performance liquid chromatography-quadrupole/time of flight
      mass spectrometer in positive mode. The obtained data were further analyzed by
      principal component and partial least-squares discriminant analysis to reveal
      differentiating metabolites. The pattern of metabolites in the serum after
      Rhizoma Coptidis exhibited distinct alterations. A total of 10 potential
      biomarkers were significantly altered in the serum and may be associated with the
      underlying mechanism. Alterations were primarily associated with phospholipid
      metabolism, fatty acid metabolism, amino acid metabolism and arachidonic acid
      metabolism. In addition, biochemical alterations in potential biomarkers were
      associated with inflammation, nitric oxide production, platelet aggregation and
      endothelial function. By analyzing and verifying the specific biomarkers,
      metabolomics may be helpful to further understand the underlying therapeutic
      mechanism of Rhizoma Coptidis. Metabolomics is a powerful tool used to
      investigate the therapeutic effects of herbal medicine with multiple targets.

PMID- 28765929
TI  - Characterization and predicted role of microRNA expression profiles associated
      with early childhood obesity.
AB  - MicroRNAs (miRNAs) are implicated in the pathogenesis of obesity. The aim of the
      present study was to characterize the miRNA profile associated with early
      childhood obesity in peripheral blood mononuclear cells (PBMCs). A total of 12
      children (6 obese and 6 lean controls) aged 36 months old to 48 months old were
      recruited. The miRNA expression profile from PBMCs was detected using the
      multiplexed NanoString nCounter system. Bioinformatics was employed to detect
      target genes and miRNA-regulated biological function. A total of 9 differentially
      expressed miRNAs were identified in obese children compared with lean children
      (P<0.05). Among the 9 miRNAs, miR-199a-3p/miR-199b-3p and miR-4454 presented at
      least a 1.5-fold change in expression. A total of 643 potential target genes were
      regulated by the three miRNAs, and 291 of the potential genes were involved in a
      protein interaction network. Gene ontology annotation indicated that 291
      potential genes were enriched in 14 biological process annotations and 2
      molecular function annotations. miRNA dysregulation may be involved in early
      childhood obesity.

PMID- 28765930
TI  - E-cadherin involvement in human lens epithelial cell transdifferentiation may be
      associated with N-cadherin.
AB  - E-cadherin, beta-catenin and N-cadherin serve key roles in the epithelial-to
      mesenchymal transition (EMT) that leads to human lens epithelial cell (LEC)
      transdifferentiation and subsequent cataract formation. The present study aimed
      to investigate the role of E-cadherin in LEC transdifferentiation. SRA01/04 human
      LECs were transfected with E-cadherin short interfering (si)RNA (E-cadherin siRNA
      group), negative control siRNA (NC group) or the transfection regent
      Lipofectamine 2000 (blank group). Reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR) was used to detect mRNA expression levels of E-cadherin,
      N-cadherin and beta-catenin, and western blot analysis was performed to measure
      the protein expression levels in the three groups. SRA01/04 cells transfected
      with E-cadherin siRNA exhibited a significant decrease in the mRNA expression
      level of E-cadherin (P<0.05) and N-cadherin (P<0.05), whereas no significant
      changes were identified for beta-catenin expression (P>0.05). Consistent with the
      results of RT-qPCR, western blotting demonstrated that the protein expression
      levels of E-cadherin and N-cadherin were notably decreased in E-cadherin siRNA
      transfected cells, whereas the protein expression level of beta-catenin remained
      unchanged. Results from the present study indicated that E-cadherin may be
      involved in human LEC transdifferentiation by affecting N-cadherin expression.

PMID- 28765931
TI  - LncRNA H19 regulates ID2 expression through competitive binding to hsa-miR-19a/b
      in acute myelocytic leukemia.
AB  - Acute myelocytic leukemia (AML) is the most common type of acute leukemia. Long
      non-coding RNAs (lncRNAs) serve an important role in regulating gene expression
      through chromatin modification, transcription and post-transcriptional
      processing. LncRNA H19 was considered as an independent prognostic marker for
      patients with tumors. The expression of lncRNA H19 was identified to be
      significantly upregulated in bone marrow samples from patients with AML-M2.
      Furthermore, it was demonstrated that the knockdown of lncRNA H19 resulted in
      increased expression of hsa-microRNA (miR)-19a/b and decreased expression of
      inhibitor of DNA binding 2 (ID2) in AML cells. The knockdown of lncRNA H19
      inhibited the proliferation of AML cells in vitro, which could be partially
      reversed by ID2 overexpression. Furthermore, the results of the bioinformatic
      analysis revealed potential hsa-miR-19a/b-3p binding sites in lncRNA H19 and ID2.
      Altogether, the results of the present study suggest that lncRNA H19 regulates
      the expression of ID2 through competitive binding to hsa-miR-19a and hsa-miR-19b,
      which may serve a role in AML cell proliferation.

PMID- 28765932
TI  - FGF18 inhibits MC3T3-E1 cell osteogenic differentiation via the ERK signaling
      pathway.
AB  - Fibroblast growth factor (FGF) 18 is a member of the FGF family and serves a key
      role in skeletal growth and development. The present study investigated the
      effect of FGF18 on pre-osteoblast MC3T3-E1 cells and the signaling pathways
      involved by performing an alkaline phosphatase (ALP) assay and reverse
      transcription-quantitative polymerase chain reaction. MC3T3-E1 cells incubated in
      a culture medium supplemented with FGF18 exhibited increased viability when
      compared with the untreated control cells. In addition, ALP activity was
      decreased in MC3T3-E1 cells treated with FGF18 plus an osteogenic medium (OM) for
      7 and 14 days when compared with untreated and OM-treated controls. Reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) results
      demonstrated that the expression of osteoblastic-associated genes was
      significantly repressed in FGF18 plus OM-treated MC3T3-E1 cells, including ALP,
      collagen type I, osteocalcin, bone sialo protein and osterix. These results
      suggested that the expression levels of genes associated with osteogenesis were
      mainly repressed. In addition, combined treatment of MC3T3-E1 cells with OM and
      FGF18 led to a significant reduction in mineral deposition when compared with the
      OM-only treated group. Furthermore, FGF18 activated the extracellular signal
      regulated kinase pathway in MC3T3-E1 cells, which may have been responsible for
      the observed decrease in the expression of osteoblastic-associated genes. In
      conclusion, the results suggest that FGF18 may be involved in MC3T3-E1 cell
      proliferation and osteoblastic differentiation.

PMID- 28765933
TI  - Gene therapy for human ovarian cancer cells using efficient expression of Fas
      gene combined with gammadeltaT cells.
AB  - Low tissue specificity and efficiency of exogenous gene expression are the two
      major obstacles in tumor-targeted gene therapy. The Fas cell surface death
      receptor (Fas)/Fas ligand pathway is one of the primary pathways responsible for
      the regulation of cell apoptosis. The aim of the present study was to explore
      whether the regulation of tumor specific promoters and a two-step transcriptional
      amplification system (TSTA) assured efficient, targeted expression of their
      downstream Fas gene in human ovarian cancer cells, and to assess the killing
      effect of gammadeltaT cells on these cells with high Fas expression. Three
      shuttle plasmids containing different control elements of the human telomerase
      reverse transcriptase (hTERT) promoter and/or TSTA were constructed and packaged
      into adenovirus 5 (Ad5) vectors for the expression of exogenous Fas gene. The
      human ovarian cancer cell line SKOV3 and a control human embryonic lung
      fibroblast cell line were transfected with Ad5-hTERT-Fas or Ad5-hTERT-TSTA-Fas.
      Fas mRNA and protein expression were examined by reverse transcription
      quantitative polymerase chain reaction and western blot analysis. gammadeltaT
      lymphocytes were isolated, cultured and mixed at different ratios with SKOV3
      cells with Fas expression in order to assess the killing effect of gammadeltaT
      cells. hTERT promoter induced the specific expression of FAS gene in SKOV3 cells,
      and the TSTA strategy increased FAS expression by 14.2-fold. The killing effect
      of gammadeltaT cells increased with the expression level of Fas and the effector
      target cell ratio. The killing rate for SKOV3 cells with high FAS expression was
      72.5% at an effector-target cell ratio of 40:1. The regulators of hTERT promoter
      and TSTA assure the efficient and targeted expression of their downstream Fas
      gene in SKOV3 cells. The killing effect of gammadeltaT cells for ovarian cancer
      cells with relatively high Fas expression was improved.

PMID- 28765934
TI  - RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and
      angiogenesis in oral squamous cell carcinoma.
AB  - Although aberrant expression of Runt-related transcription factor 3 (RUNX3)
      contributes to tumor progression and metastasis in a number of carcinomas, the
      status of RUNX3 and its correlation with prognosis in oral squamous cell
      carcinomas (OSCC) are still controversial. The aim of present study was to
      investigate the function of RUNX3 in OSCC and the underlying molecular
      mechanisms. Tissue microarray (TMA) consisting of 232 OSCC specimens was used to
      detect the expression of RUNX3 by immunohistochemistry method. The effects of
      RUNX3 restoration on OSCC cell migration and invasion were determined by wound
      healing assay, migration and Matrigel cell invasion assays. The antiangiogenic
      role of RUNX3 was analyzed by testing proliferation and tube formation of human
      umbilical vascular endothelial cells (HUVECs) cultured with conditioned medium
      from RUNX3 transfected OSCC cell lines. The activities of MMP-9 and VEGF in RUNX3
      transfected OSCC cell lines were examined by western blot and Elisa methods.
      RUNX3 expression was reduced in OSCC specimens and significantly associated with
      tumor size (P=0.002), lymph node statue (P=0.0036) and clinical stage (P=0.0001).
      Negative expression of RUNX3 correlated with worse 5-year overall and disease
      specific survival rates (P=0.0348 and P=0.0301, respectively). Furthermore, we
      found that RUNX3 restoration suppressed cell migration and invasion through
      downregulating MMP-9 expression and secretion, and exerted antiangiogenic
      capability by inhibiting VEGF activity in HN6 and Cal27 cells. These findings
      suggested that RUNX3 played a tumor suppressor role in OSCC by inhibiting cell
      migration, invasion and angiogenesis, supporting that it could be a potential
      therapeutic target for OSCC.

PMID- 28765935
TI  - FBW7 increases the chemosensitivity of pancreatic cancer cells to gemcitabine
      through upregulation of ENT1.
AB  - F-box and WD repeat domain-containing 7 (FBW7) has been characterized as a tumor
      suppressor, and its mutation or decreased expression has been observed in many
      types of human cancers. Our recent studies have uncovered that in pancreatic
      cancer, the KRAS mutation decreased FBW7 expression through phosphorylation and
      subsequent ubiquitination. Moreover, FBW7 inhibited aerobic glycolysis in
      pancreatic cancer via induction of thioredoxin-interacting protein (TXNIP), a
      mitochondrial localized tumor suppressor. The roles of FBW7 in anti-apoptosis and
      drug resistance via proteosomal degradation of myeloid cell leukemia-1 (MCL-1),
      which is an anti-apoptotic factor have been reported. However, the role of FBW7
      in the chemotherapeutic resistance of pancreatic cancer to gemcitabine has seldom
      been reported. In the present study, we demonstrated that overexpression of FBW7
      in pancreatic cancer cells rendered increased sensitivity to gemcitabine.
      Mechanistically, FBW7 promoted gemcitabine sensitivity via upregulation of
      equilibrative nucleoside transporter 1 (ENT1) at the protein level rather than
      the transcriptional level. In depth analysis demonstrated that the ENT1 protein
      level could be increased by lysosome inhibition. Taken together, our results
      demonstrated that FBW7 could be a target for improving the therapeutic efficacy
      of gemcitabine by induction of ENT1.

PMID- 28765936
TI  - Human cytomegalovirus miR-US4-5p promotes apoptosis via downregulation of p21
      activated kinase 2 in cultured cells.
AB  - The human cytomegalovirus (HCMV) encodes >=26 microRNAs (miRNAs). These miRNAs
      are utilized by HCMV to regulate its own genes in addition to the genes of the
      host cell, during infection. The present study first identified p21-activated
      kinase 2 (PAK2) as a target of hcmv-miR-US4-5p, via hybrid polymerase chain
      reaction, which was further verified using a luciferase reporter assay. The
      protein expression level of PAK2, detected via western blotting, was demonstrated
      to be directly downregulated by overexpression of hcmv-miR-US4-5p in HEK293, HELF
      and THP-1 cells. Furthermore, it was demonstrated that the PAK2 protein level in
      naturally infected HELF cells was gradually decreased at 24, 48 and 72 h post
      infection with increased hcmv-miR-US4-5p expression. The use of PAK2-specific
      small interfering RNA and an inhibitor for hcmv-miR-US4-5p, demonstrated that the
      promotion of apoptosis by hcmv-miR-US4-5p in these cells was specifically
      mediated via inhibition of PAK2 expression. These results indicated that hcmv-miR
      US4-5p may exhibit this activity during natural HCMV infection, in order to
      establish a balance between the host cell and virus.

PMID- 28765937
TI  - Oncogenic miR-100-5p is associated with cellular viability, migration and
      apoptosis in renal cell carcinoma.
AB  - As influencing factors of genesis and progression in several types of human
      tumor, microRNAs (miRs) serves roles in the regulation of tumor cell viability,
      migration, and apoptosis. The present research aimed to investigate the
      association between the function of miR-100-5p and renal cell carcinoma (RCC).
      miR-100-5p expression was determined in RCC tissue and paired normal tissue
      samples using reverse transcription-quantitative polymerase chain reaction. To
      assess the effects of miR-100-5p on cell viability, migration and apoptosis,
      multiple methods were used, including scratch wound assays, MTT assays, and flow
      cytometry. It was demonstrated that miR-100-5p was significantly upregulated in
      RCC tissue compared with in normal adjacent tissue samples. Furthermore, the
      viability and migration of 786-O and, ACHN cells tranfected with miR-100-5p was
      significantly increased compared with the negative control group. In addition,
      miR-100-5p-transfected 786-O and ACHN cells demonstrated significantly reduced
      cellular apoptotic rates compared with the negative control group. To the best of
      our knowledge, the present study is the first to report an association between
      miR-100-5p and RCC. The results of the current study suggest that tumor oncogene
      miR-100-5p could be used as a diagnostic biomarker for RCC.

PMID- 28765938
TI  - Rapamycin inhibits spermatogenesis by changing the autophagy status through
      suppressing mechanistic target of rapamycin-p70S6 kinase in male rats.
AB  - Rapamycin (sirolimus) is an antiproliferative drug that has been widely used in
      the clinic as an immunosuppressant and a potential anticancer agent. Certain
      reports have indicated that rapamycin may induce male infertility through
      impairing sperm quality. The present study investigated the mechanism of male
      infertility caused by rapamycin and examined whether withdrawal of rapamycin
      could recover the number of sperm in rats. Male Sprague-Dawley rats (n=100) were
      divided randomly into 5 groups: 3 rapamycin-treated groups (2, 4 and 6 mg/kg) and
      2 control groups [Blank and dimethyl sulfoxide (DMSO)]. Organ coefficients of the
      testes, number of sperm and hematoxylin-eosin staining analyses demonstrated that
      rapamycin treatment markedly damaged the structure of the seminiferous tubule and
      reduced the number of sperm. Immunohistochemistry of mechanistic target of
      rapamycin (mTOR) and Ki67 in testes tissue, and western blotting of
      phosphorylated-p70S6K and p70S6K, supported the hypothesis that rapamycin causes
      sperm reduction through inhibiting proliferation of spermatogonia. Unfortunately,
      24 weeks after cessation of rapamycin treatment, only the number of sperm in 2
      mg/kg group was restored back to the normal level. In addition, to the best of
      our knowledge, the present study was the first to demonstrate that low doses
      rapamycin leads to activation of autophagy in rat testes. This may be a self
      protective mechanism of the cell in response to external stress. Thus,
      spermatogenesis can be recovered in the testes from rats in the low dose group.
      High doses of rapamycin resulted in excessive consumption of autophagy proteins,
      and the damage could not be compensated. In addition, it was revealed that cell
      apoptosis increased after treatment with rapamycin. In conclusion, the present
      study demonstrated that rapamycin inhibits spermatogenesis through suppressing
      phosphorylation of p70S6K and changing the autophagy status, ultimately reducing
      the number of sperm. These findings provide important guidance for the clinical
      application of rapamycin.

PMID- 28765939
TI  - Molecular dynamics simulations of human E3 ubiquitin ligase Parkin.
AB  - Human E3 ubiquitin protein ligase parkin (Parkin) mediates mitophagy to maintain
      mitochondrial homeostasis. Parkin mutations are common genetic causes of early
      onset familial Parkinson's disease. The molecular mechanism of Parkin activation
      has been widely studied with emerging evidence suggesting an essential role of
      the phosphorylated (phospho)-ubiquitin interaction. However, the underlying mecha
      nism of the phospho-ubiquitin interaction remains elusive. In the present study,
      replica exchange molecular dynamics simulations were performed to examine the
      conformational dynamics of Parkin in monomer and phospho-ubiquitin-bound states.
      In the Parkin monomer state, high structural flexi-bilities were observed in the
      majority of regions of Parkin particularly in the loop domain between the
      ubiquitin-like (UBL) and really interesting new gene (RING)0 domain. Binding of
      phospho-ubiquitin stabilizes the RING1/RING in between RING interface but
      destabilizes the RING1-UBL interface. Furthermore, using steered molecular
      dynamics simulations of Parkin mutations, it was demonstrated that salt bridge
      interactions contribute significantly to the interdomain interactions between the
      RING1 and UBL domain. Taken together, the results of the present study revealed
      the conformational dynamics of human full-length Parkin in monomer and phospho
      ubiquitin-bound states, providing insights into designing potential therapeutics
      against Parkinson's disease.

PMID- 28765940
TI  - IL-33 restricts invasion and adhesion of trophoblast cell line JEG3 by
      downregulation of integrin alpha4beta1 and CD62L.
AB  - Interleukin-33 (IL-33) promotes migration of cancer cells through downregulating
      the expression of E-cadherin. Previous studies have demonstrated that IL-33
      stimulates the proliferation of trophoblasts. However, the effect of IL-33 on the
      adhesion and invasion of trophoblasts has not been investigated in detail. In the
      present study, the expression of IL-33 and its receptor, IL-1 receptor-like 1
      (ST2), was examined in villi from women during early pregnancy using
      immunohistochemistry. ST2 expression on human trophoblast and choriocarcinoma
      cell lines JAR, BeWo, JEG3 and HTR8 was confirmed by flow cytometry (FCM) assay.
      The effect of recombinant human IL-33 (rhIL-33) on adhesion, invasion and
      associated molecules was analyzed by cell adhesion, Matrigel invasion and FCM
      assays. The current study identified that human trophoblasts expressed IL-33 and
      ST2. RhIL-33 inhibited trophoblast invasion and adhesion, and decreased adhesion
      and invasion-associated molecules such as integrin alpha4beta1 and CD62L.
      Therefore, these results suggest that IL-33 may serve an important role in
      limiting invasion and implantation of trophoblasts by adhesion and invasion
      associated molecules, contributing to the formation of the placenta and
      maintenance of normal pregnancy during early pregnancy.

PMID- 28765941
TI  - B7-H3 is related to tumor progression in ovarian cancer.
AB  - B7-H3, a co-stimulatory molecule, has been found expressed in ovarian cancer, but
      its role and mechanism is not clear. In this study, we further verified the
      expression of B7-H3 in ovarian carcinoma and normal epithelial ovarian tissues.
      Three ovarian cancer cell lines, A2780, SKOV3 and HO8910 were selected to explore
      the effects of B7-H3 on proliferation, apoptosis, migration and invasion. We
      found that B7-H3 was mainly located in the cytoplasm of ovarian cancer cells as
      determined by immunofluorescence staining. The ability of cell invasion,
      migration, proliferation decreased after silencing B7-H3 whereas the apoptosis
      increased, which was related to the upregulation of Bax, caspase-8, cleaved
      caspase-8 and the downregulation of Bcl-2, Bcl-xl, matrix metalloproteinase-2
      (MMP2) by western blotting. In addition, B7-H3 enhanced the H08910 cell
      capacities in invasion, migration and proliferation. Expression of the
      phosphorylation signal transducer and activator of transcription 3 (pStat3)
      molecules and their upstream molecules phosphorylation Janus kinase 2 (pJak2)
      were significantly increased. In order to investigate whether B7-H3 plays a role
      in this pathway, we treated the overexpressed HO8910 cells with AG490 (inhibitors
      of Jak2). Our findings revealed that B7-H3 affect ovarian cancer progression
      through the Jak2/Stat3 pathway, indicating that B7-H3 has the potential to be a
      useful prognostic marker.

PMID- 28765942
TI  - Protein kinase C isozyme expression in right ventricular hypertrophy induced by
      pulmonary hypertension in chronically hypoxic rats.
AB  - In chronic hypoxia, pulmonary hypertension (PH) induces right ventricular
      hypertrophy (RVH). Evidence indicates that protein kinase C (PKC) serves a
      crucial role in hypoxia-induced RVH. The present study investigated PKC isoform
      specific expression and its involvement in RVH. Rats were exposed to normobaric
      hypoxia for a number of days to induce PH. PKC isoform-specific membrane
      translocation and protein expression in the myocardium were evaluated by western
      blotting and immunostaining. A total of six isoforms of conventional PKC (cPKC;
      alpha, betaI and betaII) and of novel PKC (nPKC; delta, epsilon and eta), were
      detected in the rat myocardium. Hypoxic exposure (1-21 days) induced PH with RVH
      and vascular remodeling. nPKCdelta membrane translocation at 3-7 days and
      cPKCbetaI expression at 1-21 days in the RV following hypoxic exposure were
      significantly decreased as compared with the normoxia control group. Membrane
      translocation of cPKCbetaII at 14-21 days and of nPKCeta at 7-21 days in the left
      ventricle following hypoxic exposure was significantly increased when compared
      with the control. The results of the present study suggested that the alterations
      in membrane translocation, and nPKCdelta and cPKCbetaI expression, are associated
      with RVH following PH, and the upregulation of cPKCbetaII membrane translocation
      is involved in left-sided heart failure.

PMID- 28765943
TI  - Acute and chronic effects of taurine magnesium coordination compound on cardiac
      sodium channel Nav1.5.
AB  - It has been previously demonstrated that taurine magnesium coordination compound
      (TMCC) produces antiarrhythmic effects in vivo. The present study investigated
      the acute and chronic effect of TMCC on sodium channels in HEK cells stably
      expressing human cardiac Nav1.5 sodium channels. The current amplitude,
      activation and inactivation kinetics, recovery time from inactivation, and use
      dependent block of sodium channels were analyzed using the whole-cell patch clamp
      technique. Western blotting was used to analyze Nav1.5 expression following
      chronic TMCC treatment. In HEK cells expressing Nav1.5 channels, TMCC acutely
      inhibited Na+ currents in a dose-dependent manner. In addition, acute application
      of TMCC shifted the activation and inactivation curves, and prolonged the
      recovery time from inactivation, but did not exhibit a use-dependent block of
      Nav1.5. By contrast, chronic TMCC treatment only produced a use-dependent block
      of Nav1.5 and downregulated Nav1.5 expression. The results of the present study
      suggested that TMCC may produce antiarrhythmic actions via acute inhibition of
      sodium channel currents and chronic downregulation of Nav1.5 expression.

PMID- 28765944
TI  - c-Myc promotes tumor proliferation and anti-apoptosis by repressing p21 in
      rhabdomyosarcomas.
AB  - v-myc avian myelocytomatosis viral oncogene homolog (c-Myc) is an important
      member protein of the Myc family that is important in cell cycle progression,
      apoptosis and tumorigenesis. In the present study, the role of c-Myc in
      rhabdomyosarcoma (RMS) was assessed. Firstly, expression of endogenous c-Myc and
      cyclin dependent kinase inhibitor 1A (p21) was examined in normal skeletal
      muscle, RMS specimens and TE671 RMS cells by immunohistochemistry, reverse
      transcription-quantitative polymerase chain reaction and western blotting.
      Furthermore, cell cycle progression and apoptosis were assessed in TE671 RMS
      cells following treatment with a c-Myc inhibitor, 10058-F4. The results
      demonstrated that c-Myc was overexpressed in clinical RMS tissues and TE671
      cells, with the highest expression observed in the most RMS samples. Expression
      of p21 protein and apoptosis function were increased following treatment with
      10058-F4, but no difference was observed in cell cycle progression. In
      conclusion, the present study indicated that c-Myc promotes RMS development by
      inhibiting apoptosis through repression of p21 transcription. Further studies
      will be required to evaluate c-Myc as a target for RMS clinical treatment.

PMID- 28765945
TI  - Platelet-rich plasma exhibits beneficial effects for rheumatoid arthritis mice by
      suppressing inflammatory factors.
AB  - Platelet-rich plasma (PRP) is a multifunctional blood product containing highly
      concentrated platelets, and various cell growth factors which promote cell
      proliferation and differentiation. PRP exhibited benefits in injurious articular
      cartilage repair and the removal of inflammatory factors in clinical studies.
      Rheumatoid arthritis (RA) is an autoimmune disease manifesting primarily as
      inflammatory arthritis, which is associated with notable morbidity in humans. In
      the present study, the therapeutic effects and primary mechanism of PRP on a type
      II collagen-induced arthritis (CIA) mouse model was investigated. Inflammatory
      factors interleukin (IL)-6, IL-8, IL-17, IL-1beta, tumor necrosis factor (TNF)
      alpha and interferon (IFN)-gamma were analyzed in PRP and PBS-treated groups.
      Vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF),
      insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-beta
      expression in peripheral whole blood was additionally analyzed. The therapeutic
      efficacy of PRP for RA mice was evaluated using clinical arthritis scores. The
      results of the present study demonstrated that treatment with PRP alleviated
      arthritis, and reduced humoral and cellular immune responses, leading to
      beneficial effects on histological parameters as observed using joint tissue
      histological staining. CIA mice treated with PRP exhibited downregulated
      expression of IL-6, IL-8, IL-17A, IL-1beta, TNF-alpha, receptor activator for
      nuclear factor-kappaB and IFN-gamma in inflammatory tissue. In addition, VEGF,
      PDGF, IGF-1 and TGF-beta expression in peripheral whole blood was increased
      following treatment with PRP. The serum concentration of anti-collagen antibody
      was decreased in PRP-treated CIA mice. In conclusion, CIA mice treated with PRP
      exhibited beneficial effects, including decreased joint inflammation, cartilage
      destruction and bone damage, and increased repair of joint tissue. The results of
      the present study suggested that PRP may be an effective therapeutic agent for
      RA.

PMID- 28765946
TI  - Histone demethylase PHF8 accelerates the progression of colorectal cancer and can
      be regulated by miR-488 in vitro.
AB  - Plant homeo domain finger protein 8 (PHF8), as an oncogene, has been highlighted
      in cancer development and progression. However, its clinical significance and
      underlying molecular mechanisms in colorectal cancer (CRC) remain to be fully
      elucidated. In the present study, the role of PHF8 in the progression of CRC was
      investigated. The mRNA and protein levels of PHF8 in tissues from patients with
      CRC and cell lines were detected using the reverse transcription-quantitative
      polymerase chain reaction and western blotting, respectively. Cell viability was
      analyzed using an MTT assay. The targeted genes were predicted using a
      bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Cell
      migration was evaluated using a Transwell assay. The results demonstrated that
      the expression of PHF8 was significantly increased in tumor tissues from patients
      with CRC and was correlated with tumor-node-metastasis stage. In addition, it was
      found that overexpressed PHF8 was a predictor of poor overall survival rates in
      patients with CRC. PHF8 loss-of-function significantly inhibited proliferation
      and migration, and promoted apoptosis of CRC cells. In addition, bioinformatics
      methods demonstrated that PHF8 was a putative target of microRNA (miR)-488, and
      miR-488 was able to inhibit the expression of PHF8 in CRC cells. miR-488 loss-of
      function showed increased proliferation and migration, and these effects were
      reversed by sh-PHF8 transfection in CRC cells. In vitro and in vivo experiments
      revealed that PHF8 accelerated cancer cell growth and migration, confirming the
      oncogenic role of PHF8 in human CRC. In conclusion, PHF8 and miR-488 may serve as
      CRC biomarkers for the prediction of clinical outcome and provide a target for
      the diagnosis and therapy of CRC.

PMID- 28765947
TI  - Acid ceramidase confers radioresistance to glioblastoma cells.
AB  - Glioblastoma multiforme (GBM) is the most common primary, intracranial malignancy
      of the central nervous system. The standard treatment protocol, which involves
      surgical resection, and concurrent radiation with adjuvant temozolomide (TMZ),
      still imparts a grim prognosis. Ultimately, all GBMs exhibit recurrence or
      progression, developing resistance to standard treatment. This study demonstrates
      that GBMs acquire resistance to radiation via upregulation of acid ceramidase
      (ASAH1) and sphingosine-1-phosphate (Sph-1P). Moreover, inhibition of ASAH1 and
      Sph-1P, either with humanized monoclonal antibodies, small molecule drugs (i.e.
      carmofur), or a combination of both, led to suppression of GBM cell growth. These
      results suggest that ASAH1 and Sph-1P may be excellent targets for the treatment
      of new GBMs and recurrent GBMs, especially since the latter overexpresses ASAH1.

PMID- 28765948
TI  - Transcription of seven genes in a model of interferon-gamma-induced persistent
      Chlamydia psittaci infection.
AB  - The obligate intracellular bacterium Chlamydia psittaci is the causative agent of
      psittacosis in birds and humans. The capability of this zoonotic pathogen to
      develop a persistent phase may serve a role in the chronicity of infections, in
      addition to the failure of antibiotic therapy or immunoprophylaxis. In the
      present study, a C. psittaci strain 6BC persistent infection cell model was
      induced using interferon (IFN)-gamma, alterations in the infectivity and
      morphology of the pathogen were analyzed, and the transcript profile of seven
      selected genes was analyzed. Following treatment with IFN-gamma, the infectivity
      of C. psittaci 6BC was decreased, the inclusion bodies appeared to be smaller,
      reticulate bodies were larger and the number of infectious elementary bodies was
      decreased compared with acute infection. In IFN-gamma-induced persistently
      infected cells, the relative mRNA expression levels of the genes CPSIT-0208,
      CPSIT-0310, CPSIT-0846, CPSIT-0844 and CPSIT-0594 were upregulated at 2-48 h post
      infection (p.i.). The genes CPSIT-0959 and CPSIT-0057 were downregulated at 2-36
      h p.i. The results of the present study advanced the understanding of C. psittaci
      persistent infection and demonstrated a number of previously unknown alterations
      in chlamydial gene expression, which may provide novel targets to further analyze
      this particular host-pathogen interaction.

PMID- 28765949
TI  - Identification of miRNA-mRNA crosstalk in laryngeal squamous cell carcinoma.
AB  - The aim of the present study was to elaborate the underlying pathogenesis of
      laryngeal squamous cell carcinoma (LSCC). Micro (mi) RNA and messenger (m) RNA
      expression profiling of patients with LSCC were downloaded from The Cancer Genome
      Atlas (TCGA) database. Differentially expressed miRNAs (DEMIs) and differentially
      expressed mRNAs (DEMs) were identified in LSCC compared to normal control
      tissues. The DEMs targeted by DEMIs were identified and the negative correlation
      between DEMs and DEMIs was subjected to visualization. The potential functions of
      DEMs targeted by DEMIs were annotated in Gene Ontology (GO) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) database. A total of 663 dysregulated
      DEMs (449 upregulated and 214 downregulated) and 33 DEMIs (24 upregulated and 8
      downregulated) were identified in LSCC compared with normal controls. 502
      negative correlations between DEMIs and DEMs were identified and subjected to
      construct interaction network. In the network, hsa-miR-486, -34c, -206 and -182
      had the highest connectivity with DEMs, and respectively regulated 39, 33, 28 and
      27 DEMs. DEMs targeted by DEMIs were significantly enriched in signal
      transduction, actin binding and extracellular region of GO terms and focal
      adhesion and extracellular matrix-receptor interaction of KEGG pathways. The
      present study may provide valuable information for understanding the potential
      oncogenesis mechanism in LSCC and provide the foundation work for diagnosis
      biomarkers and therapeutic targets for LSCC.

PMID- 28765950
TI  - Zinc finger protein 307 functions as a tumor-suppressor and inhibits cell
      proliferation by inducing apoptosis in hepatocellular carcinoma.
AB  - Zinc finger protein 307 (ZNF307) is a new Kruppel-associated box zinc-finger
      protein gene and a member of the zinc-finger family of transcriptional factors.
      Notably, the role of ZNF307 and its underlying mechanisms involved in
      hepatocarcinogenesis are poorly investigated. In the present study, we found that
      the expression of ZNF307 was significantly downregulated in hepatocellular
      carcinoma (HCC) tissues, compared with that in adjacent non-tumor tissues. In
      vitro studies further demonstrated that ectopic expression of ZNF307 in HCC cell
      lines Bel7402 and HCCLM3 significantly reduced cell proliferation, migration and
      invasive ability. Concordantly, knockdown of ZNF307 increased cell proliferation,
      migration and invasive ability of HCC cell lines MHCC97L and QGY7701. In vivo
      functional studies showed that upregulation of ZNF307 expression in Bel7402 cells
      led to a suppression of tumorigenicity in mice, while knockdown of ZNF307 in
      MHCC97L cells resulted in reverse. effects. Importantly, flow cytometric analysis
      showed that ZNF307 overexpression increased the incidence of apoptosis, while
      ZNF307 knockdown decreased the incidence of apoptosis. Consistently, key
      regulators in apoptosis, such as caspase-3, BAX and BCL-2 were also regulated by
      ZNF307. Therefore, our results indicate that ZNF307 may serve as a tumor
      suppressor and inhibits cell proliferation of HCC via inducing apoptosis.

PMID- 28765951
TI  - Pseudolaric acid B inhibits neuroglioma cell proliferation through DNA damage
      response.
AB  - Human neuroglioma is one of the most common malignant intracranial tumors in
      neurosurgery, and accounts for more than 50% of all brain cancer cases. Thus, a
      clinically effective drug with which to treat neuroglioma is urgently required.
      Pseudolaric acid B (PAB), a diterpene acid isolated from the root and trunk bark
      of Pseudolarix kaempferi Gordon (Pinaceae), was found to inhibit cell growth in a
      variety of cancer cell lines, but to date the effect of PAB on neuroglioma
      remains unclear. MTT analysis confirmed that PAB inhibited neuroglioma A172 cell
      growth in a time- and dose-dependent manner. In addition, PAB influenced the
      aggregation of tubulin in A172 cells. Meanwhile following PAB treatment, a higher
      percentage of cells accumulated in the G2/M phase from 12 to 48 h, while at 36 h,
      cell cycle slippage into the G0/G1 phase, and at 48 h, slippage into the S phase
      was observed using flow cytometric analysis. Corresponding protein expression was
      consistent with the cell cycle alteration as detected by western blotting, and it
      was speculated that cell cycle slippage was related to reduced effectiveness of
      PAB which warrants further investigation. Meanwhile PAB induced cell death by
      regulating p38, ERK and JNK expression and activating the DNA damage response.
      Therefore, PAB plays an antitumor role in A172 cells, and may be a candidate drug
      for neuroglioma therapy.

PMID- 28765952
TI  - mTOR signaling promotes foam cell formation and inhibits foam cell egress through
      suppressing the SIRT1 signaling pathway.
AB  - Atherosclerosis (AS) is a chronic immuno-inflammatory disease accompanied by
      dyslipidemia. The authors previously demonstrated that sirtuin 1 (SIRT1) may
      prevent atherogenesis through influencing the liver X receptor/C-C chemokine
      receptor type 7/nuclear factor-kappaB (LXR-CCR7/NF-kappaB) signaling pathway.
      Previous studies have suggested a role for mammalian target of rapamycin (mTOR)
      signaling in the pathogenesis of cardiovascular diseases. The present study
      investigated the potential association between mTOR signaling and SIRT1-LXR
      CCR7/NF-kappaB signaling (SIRT1 signaling) in AS pathogenesis. To induce foam
      cell formation, U937 cells were differentiated into macrophages by exposure to
      phorbol 12-myristate 13-acetate (PMA) for 24 h, followed by treatment with
      palmitate and oxidized low density lipoprotein for a further 24 h. Oil red O
      staining revealed a large accumulation of lipid droplets present in foam cells.
      Western blot analysis demonstrated increased protein levels of phosphorylated (p)
      mTOR and its downstream factor p-ribosomal protein S6 kinase (p70S6K). Reverse
      transcription-quantitative polymerase chain reaction and western blot analyses
      additionally revealed decreased expression of SIRT1, LXRalpha and CCR7 and
      increased expression of NF-kappaB and its downstream factor tumor necrosis factor
      alpha (TNF-alpha) in an atherogenetic condition induced by lysophosphatidic acid
      (LPA). In addition, abundant lipid droplets accumulated in U937-LPA-treated foam
      cells. Rapamycin, an mTOR inhibitor, suppressed the expression and activity of
      mTOR and p70S6K, however enhanced expression of SIRT1, LXRalpha, and CCR7.
      Conversely, rapamycin deceased TNF-alpha and NF-kappaB activity, the latter of
      which was further confirmed by immunofluorescence analysis demonstrating
      increased levels of NF-kappaB present in the cytoplasm compared with the nucleus.
      The findings of the present study suggest that mTOR signaling promotes foam cell
      formation and inhibits foam cell egress via suppression of SIRT1 signaling.

PMID- 28765953
TI  - Atorvastatin protects cardiomyocytes against OGD/R-induced apoptosis by
      inhibiting miR-199a-5p.
AB  - The present study aimed to evaluate the protective effects of atorvastatin
      against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its
      underlying mechanisms. The direct cytotoxic effects of oxygen-glucose
      deprivation/reperfusion (OGD/R) on cardiomyocytes with and without atorvastatin
      pretreatment were evaluated. The effects of atorvastatin on the expression of
      glycogen synthase kinase-3beta (GSK-3beta) and microRNA (miR)-199a-5p were
      determined using reverse transcription-quantitative polymerase chain reaction (RT
      qPCR) and western blot analyses. In addition, the expression levels of GSK-3beta
      in cells with miR-199a-5p upregulation and downregulation were detected using RT
      qPCR, western blot and immunohistochemical analyses. Pretreatment with
      atorvastatin significantly improved the recovery of cell viability from OGD/R
      (P<0.05). In addition, atorvastatin pretreatment significantly increased the
      expression of GSK-3beta at the mRNA and protein levels, and the expression of miR
      199a-5p at the mRNA level (all P<0.05). The upregulation and downregulation of
      miR-199a-5p respectively decreased and increased the expression of GSK-3beta at
      the mRNA and protein levels. These results suggested that atorvastatin provided
      cardioprotective effects against I/R injury via increasing the expression of GSK
      3beta through the inhibition of miR-199a-5p.

PMID- 28765954
TI  - In vitro reconstitution of interactions in the CARD9 signalosome.
AB  - The caspase-associated recruitment domain (CARD)-containing protein 9 (CARD9)
      signalosome is composed of CARD9, B-cell CLL/lymphoma 10 (BCL10) and mucosa
      associated lymphoid tissue lymphoma translocation protein 1 (MALT1). The CARD9
      signalosome has been reported to exert critical functions in the immunoreceptor
      tyrosine-based activation motif-coupled receptor-mediated activation of myeloid
      cells, through nuclear factor-kappaB pathways during innate immunity processes.
      During CARD9 signalosome assembly, BCL10 has been revealed to function as an
      adaptor protein and to interact with CARD9 via CARD-CARD interactions; BCL10 also
      interacts with MALT1 via its C-terminal Ser/Thr-rich region and the first
      immunoglobulin domain of MALT1. The CARD9 signalosome is implicated in critical
      biological processes; however, its structural and biochemical characteristics
      have yet to be elucidated. In the present study, CARD9 and BCL10 CARDs were
      successfully purified and characterized, and their biochemical properties were
      investigated. In addition, CARD9-BCL10 complexes were reconstituted in vitro
      under low salt and pH conditions. Furthermore, based on structural modeling data,
      a scheme was proposed to describe the interactions between CARD9 and BCL10. This
      provides a further understanding of the mechanism of how the CARD9 signalosome
      may be assembled.

PMID- 28765955
TI  - GABAergic ventrolateral pre-optic nucleus neurons are involved in the mediation
      of the anesthetic hypnosis induced by propofol.
AB  - Intravenous anesthetics have been used clinically to induce unconsciousness for
      seventeen decades, however the mechanism of anesthetic-induced unconsciousness
      remains to be fully elucidated. It has previously been demonstrated that
      anesthetics exert sedative effects by acting on endoge-nous sleep-arousal
      circuits. However, few studies focus on the ventrolateral pre-optic (VLPO) to
      locus coeruleus (LC) sleep-arousal pathway. The present study aimed to
      investigate if VLPO is involved in unconsciousness induced by propofol. The
      present study additionally investigated if the inhibitory effect of propofol on
      LC neurons was mediated by activating VLPO neurons. Microinjection, target lesion
      and extracellular single-unit recordings were used to study the role of the VLPO
      LC pathway in propofol anesthesia. The results demonstrated that GABAA agonist
      (THIP) or GABAA antagonist (gabazine) microinjections into VLPO altered the time
      of loss of righting reflex and the time of recovery of righting reflex.
      Furthermore, propofol suppressed the spontaneous firing activity of LC
      noradrenergic neurons. There was no significant difference observed in firing
      activity between VLPO sham lesion and VLPO lesion rats. The findings indicate
      that VLPO neurons are important in propofol-induced unconsciousness, however are
      unlikely to contribute to the inhibitory effect of propofol on LC spontaneous
      firing activity.

PMID- 28765956
TI  - Anti-CD20 monoclonal antibody combined with adenovirus vector-mediated IL-10
      regulates spleen CD4+/CD8+ T cells and T-bet/GATA-3 expression in NOD mice.
AB  - Type 1 diabetes (T1D) is an autoimmune disease characterized by a selective
      destruction of insulin-secreting beta-cells. Both T cells and B cells serve a
      crucial role in pathogenesis and development of T1D. CD20 is a specific membrane
      antigen of B lymphocytes, while interleukin (IL)-10 is an important cytokine
      secreted by T helper 2 cells and has a short half-life in vivo. The combined
      effect of anti-CD20 and IL-10 on immune function of mice with T1D remains
      unknown. In the present study, 30 non-obese diabetic (NOD) mice were treated with
      anti-CD20 and adenoviral vector-mediated interleukin-10 (Ad-mIL-10) therapy.
      Alterations in CD4+, CD8+, CD4+CD25+Foxp3+ T cells, T-box expressed in T-cells (T
      bet), GATA-binding protein-3 (GATA-3) interferon-gamma (IFN-gamma) and IL-4 were
      detected by flow cytometry, reverse transcription-quantitative polymerase chain
      reaction in NOD mice spleen tissue. The present results suggested that anti-CD20
      and IL-10 treatment in NOD mice can modulate the immune functions by upregulating
      GATA-3 and IL-4 expression as well as downregulating T-bet and IFN-gamma
      expression, which are involved in the pathogenesis of T1D. The current findings
      may provide a potential method for T1D treatment and a novel preventive therapy
      for T1D. Combination of anti-CD20 and Ad-mIL-10 treatment had not only immune
      regulatory effects but also protective effects on islet beta-cells in NOD mice
      with T1DM at the early stages, by regulating T-bet/GATA-3 expression and Th1/Th2
      cell differentiation, which has the potential for diabetes prevention and
      therapy.

PMID- 28765957
TI  - Knockdown of JARID2 inhibits the proliferation and invasion of ovarian cancer
      through the PI3K/Akt signaling pathway.
AB  - Protein Jumonji (JARID2), a member of the family of JmjC domain-containing
      proteins, has been reported to serve an important role in tumor growth and
      metastasis. However, the expression pattern and role of JARID2 in ovarian cancer
      remains unclear. Therefore, in the present study, the role of JARID2 in ovarian
      cancer was investigated, as well as the underlying mechanisms. The results of the
      present study demonstrated that the expression of JARID2 is upregulated in human
      ovarian cancer cell lines. Furthermore, downregulation of JARID2 significantly
      suppressed proliferation, migration, invasion and epithelial-mesenchymal
      transition in human ovarian cancer cells. Mechanistically, downregulation of
      JARID2 decreased the protein expression levels of phosphorylated phosphoinositide
      3-kinase (PI3K) and protein kinase B (Akt) in ovarian cancer cells. In conclusion
      the observations suggested that knockdown of JARID2 inhibited proliferation,
      migration and invasion in vitro through the inactivation of the PI3K/Akt
      signaling pathway. Therefore, JARID2 may represent a potential therapeutic target
      for the treatment of ovarian cancer.

PMID- 28765958
TI  - IL-12 induces autophagy in human breast cancer cells through AMPK and the
      PI3K/Akt pathway.
AB  - Interleukin-12 (IL-12) serves an important role in immune responses and antitumor
      activity. The study of the association between autophagy and cancer cells remains
      controversial. The present study aimed to investigate the effect of IL-12 on
      autophagy in the human breast cancer cell lines MDA-MB-231 and MCF-7, and the
      possible molecular mechanism. Breast cancer cells were treated with different
      concentrations of recombinant IL-12. The expression of the autophagy-associated
      protein microtubule-associated protein light chain 3 (LC3) was determined using
      western blot analysis, fluorescein isothiocyanate-labeled LC3 was detected using
      fluorescence microscopy and autophagosomes were examined using transmission
      electron microscopy. Alterations in the phosphatidylinositol 3-kinase/Rac-alpha
      serine/threonine protein kinase (PI3K/Akt) and 5'-AMP-activated protein kinase
      subunit beta-1 (AMPK) pathways, in addition to pathway-associated proteins, were
      detected using western blotting, following treatment with IL-12 and pretreatment
      with the PI3K/Akt activator insulin-like growth factor or the AMPK inhibitor
      compound C. It was observed that IL-12 was able to upregulate the expression of
      the autophagy-associated protein LC3 in a concentration- and time-dependent
      manner, and induce the formation of autophagosomes in the two cell lines, and
      that the above effects involved the inhibition of the PI3K/Akt signaling pathway
      and the activation of the AMPK signaling pathway.

PMID- 28765959
TI  - MicroRNA-21 regulates the proliferation and apoptosis of cervical cancer cells
      via tumor necrosis factor-alpha.
AB  - The proliferation and apoptosis of tumor cells are regulated by a variety of
      microRNAs (miRs). miR-21 can inhibit the apoptosis of cancer cells in vitro.
      Tumor necrosis factor alpha (TNF-alpha) serves an important role in the induction
      of proliferation of cervical cancer cells. Previous studies have demonstrated
      that the expression level of miR-21 is associated with TNF-alpha expression in
      alveolar macrophages. However, to the best of our knowledge, whether miR-21
      regulates TNF-alpha in cervical cells has not been reported. The present study
      was designed to investigate whether miR-21 regulates TNF-alpha expression,
      proliferation and apoptosis of cervical cancer cells. miR-21, miR-21 inhibitor
      and control miRNA were synthesized and transfected into HeLa cervical cancer
      cells. Reverse transcription-quantitative polymerase chain reaction was used to
      measure the expression levels of miR-21 and TNF-alpha at the mRNA level. Western
      blotting was used to measure the expression levels of TNF-alpha at the protein
      level. MTT assay and Hoechest-33342 staining were used to measure the
      proliferation and apoptosis of HeLa cells. miR-21 was identified to upregulate
      the mRNA and protein expression levels of TNF-alpha. Furthermore, upregulation of
      TNF-alpha enhanced the proliferation capability of HeLa cells. Changes in the
      expression levels of miR-21 and TNF-alpha did not significantly affect the
      apoptosis of Hela cells. In conclusion, the present study demonstrated that miR
      21 regulates the expression of TNF-alpha in HeLa cells. Additionally, the
      expression level of TNF-alpha was positively associated with the proliferation
      capability of Hela cells, but not apoptosis. Therefore, miR-21 regulates the
      proliferation of HeLa cells through regulation of TNF-alpha. These results
      provide novel potential therapeutic targets for the treatment of cervical cancer.

PMID- 28765960
TI  - MicroRNA-616 promotes the growth and metastasis of non-small cell lung cancer by
      targeting SOX7.
AB  - MicroRNAs (miRNAs) are a group of important regulators in human types of cancer
      including non-small cell lung cancer (NSCLC). miR-616 has been found to be a
      novel cancer-related miRNA. However, the expression and biological function of
      miR-616 in NSCLC have not been investigated. In this study, qRT-PCR was performed
      to evaluate the level of miR-616 in NSCLC tissues. MTT, BrdU and Transwell assay
      were used to investigate the proliferation and metastasis ability of NSCLC cells.
      Subcutaneous injection model and tail vein injection model were used to evaluate
      the effect of miR-616 on the in vivo growth and metastasis of NSCLC cells. It was
      also found that the expression level of miR-616 was increased in NSCLC tissues
      and cell lines. Patients with a high level of miR-616 had a significantly shorter
      overall survival and disease-free survival. Functionally, miR-616 overexpression
      promoted while miR-616 knockdown inhibited the proliferation, migration and
      invasion of NSCLC cells. Moreover, miR-616 overexpression enhanced the
      subcutaneous growth and lung metastasis of NSCLC cells in nude mice.
      Mechanistically, SOX7 was confirmed to be the downstream target of miR-616 in
      NSCLC cells. Forced expression of SOX7 prevented the promoting effects of miR-616
      overexpression on the proliferation and metastasis of NSCLC cells, while
      knockdown of SOX7 reversed the inhibitory effects of miR-616 knockdown on the
      proliferation and metastasis of NSCLC cells. In conclusion, the present study
      indicates that miR-616 is a promising biomarker and therapeutic target in NSCLC.

PMID- 28765961
TI  - Upregulation of microRNA-25-3p inhibits proliferation, migration and invasion of
      osteosarcoma cells in vitro by directly targeting SOX4.
AB  - Osteosarcoma (OS) is among the most common primary tumors of bone tissue, and
      occurs primarily in children and young adults. Despite the development of novel
      therapeutic approaches, the prognosis of OS remains poor. MicroRNAs (miRNAs) are
      involved in the development and progression of various types of human cancer and
      may have potential as novel therapeutic targets for cancer treatment. The present
      study aimed to investigate the expression and biological functions of miRNA-25-3p
      in OS, and explore the molecular mechanisms underlying its actions. In the
      present study, miRNA-25-3p was detected in OS tissues and cell lines. The
      functional roles of miRNA-25-3p in OS cells were evaluated using a Cell Counting
      Kit 8 assay and cellular migration and invasion assays. The molecular mechanisms
      underlying the tumor-suppressing roles of miRNA-25-3p in OS were explored using
      bioinformatics analysis, luciferase reporter assay, western blotting and the
      reverse transcription-quantitative polymerase chain reaction. The expression of
      miRNA-25-3p was revealed to be downregulated in OS tissues and cell lines
      compared with non-tumor bone tissues and normal osteoblasts, respectively. miRNA
      25-3p overexpression was demonstrated to significantly suppress the
      proliferation, migration and invasion of OS cells in vitro. In addition, sex
      determining region-related high mobility group box (SOX) 4 was identified as a
      direct target gene of miRNA-25-3p, and was further investigated. Similarly to
      miRNA-25-3p overexpression, SOX4 knockdown was demonstrated to suppress OS cell
      proliferation, migration and invasion. Furthermore, SOX4 expression was revealed
      to be significantly upregulated in OS tissues compared with in adjacent non-tumor
      bone tissues, and Spearman's correlation analysis indicated a negative
      correlation between SOX4 mRNA and miRNA-25-3p expression levels in OS tissues.
      The present findings suggested that miRNA-25-3p may act as a tumor suppressor by
      targeting SOX4 expression in bone tissue. Therefore, miRNA-25-3p may have
      potential as a novel therapeutic target for the treatment of patients with OS.

PMID- 28765962
TI  - SIRT1 activation inhibits hyperglycemia-induced apoptosis by reducing oxidative
      stress and mitochondrial dysfunction in human endothelial cells.
AB  - Sustained hyperglycemic stimulation of vascular cells is involved in the
      pathogenesis of diabetes mellitus-induced cardiovascular complications. Silent
      information regulator T1 (SIRT1), a mammalian sirtuin, has been previously
      recognized to protect endothelial cells against hyperglycemia-induced oxidative
      stress. In the present study, human umbilical vein endothelial cells (HUV-EC-C)
      were treated with D-glucose, and the levels of oxidative stress, mitochondrial
      dysfunction, the rate of apoptosis and SIRT1 activity were measured. The effect
      of manipulated SIRT1 activity on hyperglycemia-induced oxidative stress,
      mitochondrial dysfunction and apoptosis was then assessed using the SIRT1
      activator, resveratrol (RSV), and the SIRT1 inhibitor, sirtinol. The present
      study confirmed that hyperglycemia promotes oxidative stress and mitochondrial
      dysfunction in HUV-EC-C cells. The accumulation of reactive oxygen species, the
      swelling of mitochondria, the ratio of adenosine 5'-diphosphate to adenosine 5'
      triphosphate and localized mitochondrial superoxide levels were all increased
      following D-glucose treatment, whereas the mitochondrial membrane potential was
      significantly reduced by >50 mg/ml D-glucose treatment. In addition,
      hyperglycemia was confirmed to induce apoptosis in HUV-EC-C cells. Furthermore,
      the results confirmed the prevention and aggravation of hyperglycemia-induced
      apoptosis by RSV treatment and sirtinol treatment, via the amelioration and
      enhancement of oxidative stress and mitochondrial dysfunction in HUV-EC-C cells,
      respectively. In conclusion, the present study revealed that hyperglycemia
      promotes oxidative stress, mitochondrial dysfunction and apoptosis in HUV-EC-C
      cells, and manipulation of SIRT1 activity regulated hyperglycemia-induced
      mitochondrial dysfunction and apoptosis in HUV-EC-C cells. The data revealed the
      protective effect of SIRT1 against hyperglycemia-induced apoptosis via the
      alleviation of mitochondrial dysfunction and oxidative stress.

PMID- 28765963
TI  - Suppression of TAFI by siRNA inhibits invasion and migration of breast cancer
      cells.
AB  - Human thrombin activatable fibrinolysis inhibitor (TAFI), also known as
      carboxypeptidase B2 (CPB2), is a procarboxypeptidase enzyme. The purpose of the
      present study was to observe the expression of TAFI in breast cancer (BC) and
      breast cancer cell (BCC) lines and to investigate the effect of TAFI suppression
      by small interfering (si)RNA gene silencing on invasion and migration of BCC
      lines. A significant increase in TAFI level was identified by immunohistochemical
      analysis in BC tissues compared with normal breast tissues. TAFI suppression also
      inhibited cell viability, invasion and migration ability as demonstrated by MTT,
      Transwell chamber, and wound scratch assays, respectively (P<0.05). The data
      suggested that suppression of TAFI by siRNA inhibits invasion and migration of
      breast cancer cells and that TAFI may be a new target for breast cancer therapy.

PMID- 28765964
TI  - Overexpression of long non-coding RNA differentiation antagonizing non-protein
      coding RNA inhibits the proliferation, migration and invasion and promotes
      apoptosis of renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is the third most common cancer in the urological
      system; however, the pathogenesis remains unknown. Accumulating evidence has
      demonstrated that long non-coding RNAs are dysregulated in various tumors and
      serves an important role in tumorigenesis and development. In the present study,
      expression of lncRNA differentiation antagonizing non-protein coding RNA (DANCR)
      in 24 paired RCC and adjacent normal tissues was detected by reverse
      transcription-quantitative polymerase chain reaction. The results revealed that
      DANCR is downregulated in RCC tissues compared with adjacent normal tissues.
      Subsequent study revealed that overexpression of lncRNA DANCR by transfection of
      pcDNA3.1-DANCR could suppress 786-O and ACHN (RCC cell) proliferation, migration
      and invasion, and induce apoptosis compared with cells transfected with the
      pcDNA3.1 vector. The results revealed that DANCR functions as a tumor suppressor
      in RCC. In conclusion, the present study, to the best of our knowledge, was the
      first to reveal DANCR as a tumor suppressor. The results implicate DANCR as a
      potential biomarker of RCC, and further study will be focused on the clinical
      significance and signaling pathways of DANCR.

PMID- 28765965
TI  - Downregulation of SMP30 in senescent human lens epithelial cells.
AB  - Senescence marker protein 30 (SMP30) has been reported to serve antiapoptotic and
      antioxidant roles, as well as roles in Ca2+ regulation, and may be involved in
      the occurrence and development of cataract. The present study aimed to
      investigate the expression of SMP30 in senescent human lens epithelial cells
      (HLECs) and explored the relationship between SMP30 and aging. SRA01/04 cells, a
      HLEC line, were treated with H2O2 to mimic aging, and cell morphological changes
      were observed by microscopy and cell activity was exami-ned by MTT assay,
      senescence-associated-beta-galactosidase (SA-beta-Gal) staining and cell cycle
      analysis. The expression of SMP30 mRNA and protein was measured by reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) and western
      blotting. Following prolonged low-dose H2O2 exposure, cells exhibited senescence
      related morphological changes, reduced growth activity, increased SA-beta-Gal
      positive staining and cell cycle arrest in the S and G2/M phases. SMP30 mRNA
      expression levels were significantly downregulated following exposure to 75 and
      100 uM H2O2, and the protein expression levels in the same groups were decreased
      by >6-fold compared with the control untreated cells. However, no significant
      change was observed in SMP30 expression in the 25 and 50 uM H2O2 exposure groups.
      These results suggest that, in the early stage of senescence induced by H2O2
      mediated chronic oxidative stress, there may be no significant change in SMP30
      expression, but when the oxidative stress increases and senescence is aggravated,
      SMP30 may be significantly downregulated in the senescent HLECs. The present
      study indicates that SMP30 may be an important factor involved in the aging
      process of HLECs and the development of cataract.

PMID- 28765966
TI  - Aliskiren has chondroprotective efficacy in a rat model of osteoarthritis through
      suppression of the local renin-angiotensin system.
AB  - The local renin-angiotensin system (RAS) has been reported to have an important
      role in the pathogenesis and progression of metabolic bone diseases, including
      osteoarthritis (OA). Aliskiren is the first in a new class of orally effective
      direct renin inhibitors and is approved for the treatment of hypertension in
      humans. However, its efficacy in patients with OA is unknown. A rat model of OA
      was induced to investigate the potential efficacy of aliskiren. Effects of
      aliskiren on the cartilage structure were detected by safranin O staining and its
      effects on the widths of the proliferation zone and hypertrophic zone (HZ) of
      chondrocytes were analyzed by Masson's staining. Tartate-resistant acid
      phosphatase staining was used to evaluate the effects of aliskiren on osteoclasts
      in the chondrocytes. Relative histological analyses were performed. Additionally,
      the expression levels of factors associated with osteoclast differentiation
      (receptor activator of nuclear factor kappaB ligand and osteoprotegerin),
      articular cartilage destruction [tumor necrosis factor-alpha (TNF-alpha) and
      matrix metalloproteinase 9] and osteoblast differentiation [runt related
      transcription factor 2 (Runx2)], along with RAS components (renin, renin
      receptor, angiotensin type 1 receptor (AT1R), AT2R, angiotensin converting enzyme
      (ACE) and angiotensin II (Ang II)] were detected in samples from the proximal
      tibias. Aliskiren did not fully suppress the inflammatory reaction in OA model
      animals and had marginal regulatory effects on biochemical bone markers induced
      by OA. However, aliskiren attenuated cartilage destruction, abnormal cartilage
      cellularity and the expansion of the HZ of chondrocytes, and significantly
      attenuated the expression of interleukin-1, TNF-alpha, Runx2 and procollagen type
      I N-terminal propeptide. These chondroprotective properties were accompanied by
      reductions in the levels of RAS components (renin, Ang II, ACE and AT1R),
      indicating that aliskiren exerts multiple effects of on bone formation,
      osteoblast differentiation and articular cartilage protection via the RAS. OA
      activates the local bone RAS, inhibits bone formation and stimulates bone
      resorption. Aliskiren, a renin inhibitor, demonstrated chondroprotective efficacy
      in a rat model of OA through suppression of the local RAS.

PMID- 28765967
TI  - Influenza virus non-structural protein 1 inhibits the production of interferon
      beta of alveolar epithelial cells upon the infection of influenza A H1N1.
AB  - Influenza A affects a large population worldwide. Influenza virus evades immune
      responses via various mechanisms, including through the modification of the
      immune microenvironment. Influenza virus non-structural protein 1 (NS1) encoded
      by the virus genome inhibits type I interferon (IFN) signaling pathways, which is
      essential for viral clearance. However, the precise mechanisms of NS1-mediated
      immune suppression remain poorly understood. The results of the present study
      demonstrated that mice infected with NS1-expressing influenza A H1N1 virus had
      lower expression levels of IFNbeta in the lung. In addition, it was revealed that
      the human alveolar epithelial A549 cell line infected with influenza virus A H1N1
      produced antiviral IFNbeta. The production of IFNbeta during infection was
      demonstrated to be a self-dependent autocrine process. A549 cells transfected
      with H1N1 NS1 lost the ability to produce IFNbeta upon H1N1 infection or IFNbeta
      stimulation. NS1 inhibited the expression of IFN receptors. Furthermore, NS1
      inhibited the activation of signal transducers and activators of transcription
      (STAT)1 and STAT2, as well as the consequent IFNbeta production. These data
      indicate that NS1 serves an important role during virus evasion by affecting the
      production of IFNbeta via multiple mechanisms.

PMID- 28765968
TI  - Downregulation of CCL2 induced by the upregulation of microRNA-206 is associated
      with the severity of HEV71 encephalitis.
AB  - MicroRNAs (miRNAs) have been investigated widely as key regulators of gene
      expression in different diseases by affecting the miRNA-mediated regulatory
      function. Human enterovirus 71 (HEV71) can cause a series of human diseases,
      including encephalitis. Chemokine (C-C motif) ligand 2 (CCL2) is one of the
      important genes involved in regulating inflammation. However, the mechanisms
      underlying HEV71 encephalitis mediated by CCL2 remain to be elucidated. In the
      present study, reverse transcription-quantitative polymerase chain reaction
      analysis was used to determine the expression level of miR-206 and the mRNA
      expression of CCL2 in samples. Western blot analysis was used to detect the
      protein levels of CCL2. A luciferase assay was used to verify the miR-206 target
      site in CCL2. A CCK-8 assay and flow cytometry were used to determine cell
      proliferation and apoptosis. The results demonstrated that miR-206 was
      downregulated in severe HEV71 encephalitis. Using bioinformatics analysis, miR
      206 was predicted to target the human CCL2 3'-untranslated region (3'-UTR). A
      dual-luciferase assay demonstrated that miR-206 downregulated the expression of
      CCL2 by directly targeting its 3'-UTR, whereas CCL2 3'-UTR mutations completely
      eliminated its interaction with miR-206. The expression levels of miR-206 and
      CCL2 were inversely correlated in cerebrospinal fluid. The expression of
      exogenous miRNA, which mimicked miR-206 miRNA, decreased the protein and mRNA
      levels of CCL2, whereas the suppression of endogenous miR-206 resulted in an
      increase of the protein and mRNA levels of CCL2. The present study also found
      that miR-206 promoted NPC cell proliferation and reduced the apoptosis of NPC
      cells via CCL2. The mechanism is likely to involve suppression of the expression
      of miR-206 and upregulation of the expression of CCL2, important in regulating
      the progress of HEV71 encephalitis. In conclusion, miR-206 may be useful in the
      prognosis and treatment of HEV71 encephalitis.

PMID- 28765969
TI  - AMPK activation restores ischemic post-conditioning cardioprotection in STZ
      induced type 1 diabetic rats: Role of autophagy.
AB  - Although the mechanism remains unclear, ischemic post-conditioning (IPO) is a
      promising approach to combat myocardial ischemia reperfusion (IR) injury;
      however, it has been proven ineffective in diabetes. The present study aimed to
      identify whether hyperglycemia-induced AMP-activated protein kinase (AMPK)
      inhibition contributes to the ineffectiveness of IPO via autophagy attenuation in
      diabetic hearts. Diabetic and non-diabetic rats were subjected to myocardial IR
      and/or IPO with/without treatment with the AMPK activator A-769662 and/or
      autophagy inhibitor 3-methyladenine (3-MA). Rat cardiomyocyte H9c2 cells were
      pretreated with A-769662 and/or 3-MA, and subjected to hypoxia reoxygenation (HR)
      or hypoxia post-conditioning (HPO). The degree of injury to the myocardium/cells,
      oxidative stress, AMPK/mammalian target of rapamycin (mTOR) signaling and
      autophagy status were analyzed. In diabetic rats the myocardial infarct size, and
      creatine kinase-MB and malondialdehyde release, were increased compared with non
      diabetic rats, concomitant with increased cardiac dysfunction and decreased
      cardiac superoxide dismutase activity, AMPK phosphorylation and autophagy
      following IR. IPO attenuated myocardial infarct size, increased AMPK
      phosphorylation and enhanced autophagy in non-diabetic animals. A-769662 (6.0
      mg/kg) restored IPO cardioprotection in diabetic rats. In vitro, HPO combined
      with A-769662 decreased HR injury in H9c2 cells exposed to high glucose, as
      evidenced by decreased lactic dehydrogenase expression and oxidative stress,
      accompanied by increased cell viability and autophagy. The A-769662-mediated
      restoration of IPO/HPO cardioprotection was completely reversed by treatment with
      the autophagy inhibitor 3-MA. In conclusion, AMPK inhibition, by decreasing
      autophagy, may be a mechanism through which diabetic hearts are rendered
      unresponsive to IPO cardioprotection.

PMID- 28765970
TI  - BMP-7 enhances SnoN mRNA expression in renal tubular epithelial cells under high
      glucose conditions.
AB  - The present study aimed to identify any association between bone morphogenetic
      protein-7 (BMP-7) and the expression of the transcriptional co-repressor Ski
      related novel protein N (SnoN), in addition to alterations in tubulointerstitial
      fibrosis, during the development and progression of diabetic nephropathy (DN).
      Streptozotocin was injected into the tail veins of 20 healthy and specific
      pathogen-free male Sprague-Dawley rats. The rats were sacrificed to detect the
      appropriate biochemical indicators of renal pathological alterations following 24
      weeks. Then, various doses of human recombinant BMP-7 were added to high glucose
      cultured NRK-52E cells. Immunohistochemistry, immunofluorescence staining and
      western blotting were used to determine the expression of SnoN, BMP-7, Smad
      ubiquitin regulatory factor (Smurf)2, Arkadia, E-cadherin, alpha-smooth muscle
      actin and Collagen III. Reverse transcription-quantitative polymerase chain
      reaction was used to detect SnoN mRNA expression. With the progression of DN, the
      expression of BMP-7 in rat renal tissue was downregulated, whereas the expression
      of Smurf2 and Arkadia increased. Furthermore, the expression of SnoN mRNA
      increased however the expression of SnoN protein decreased, accompanied by renal
      tubular epithelial cell mesenchymal transition, extracellular matrix (ECM)
      deposition and severe renal function disorder. The exogenous recombinant human
      BMP-7 alleviated high glucose-induced phenotypic transformation and ECM synthesis
      of NRK-52E in vitro and upregulated SnoN transcription and protein expression,
      however no effect was observed on the expression of Smurf2 and Arkadia. BMP-7 may
      ameliorate DN and renal fibrosis via increasing the expression of SnoN mRNA and
      protein in renal tubular epithelial cells, rather than directly inhibiting the
      degradation of SnoN by E3 ubiquitin ligase.

PMID- 28765971
TI  - Identification of key genes and pathways in Parkinson's disease through
      integrated analysis.
AB  - Parkinson's disease (PD) is a progressive, degene-rative neurological disease,
      typically characterized by tremors and muscle rigidity. The present study aimed
      to identify differe-ntially expressed genes (DEGs) between patients with PD and
      healthy patients, and clarify their association with additional biological
      processes that may regulate factors that lead to PD. An integrated analysis of
      publicly available Gene Expression Omnibus datasets of PD was performed. DEGs
      were identified between PD and normal blood samples. Gene Ontology enrichment and
      Kyoto Encyclopedia of Genes and Genomes pathway analyses, as well as protein
      protein interaction (PPI) networks were used to predict the functions of
      identified DEGs. Reverse transcription-quantitative polymerase chain reaction (RT
      qPCR) was performed to validate the predicted expression levels of identified
      DEGs in whole blood samples obtained from patients with PD and normal healthy
      controls. A total of 292DEGs were identified between the PD and normal blood
      samples. Of these, 156 genes were significantly upregulated and 136 genes were
      significantly downregulated in PD samples following integrated analysis of four
      PD expression datasets. The 10 most upregulated and downregulated genes were used
      to construct a PPI network, where ubiquitin C-terminal hydrolase L1 (UCHL1), 3
      phosphoinositide dependent protein kinase 1 (PDPK1) and protein kinase cAMP
      activated catalytic subunit beta (PRKACB) demonstrated the highest connectivity
      in the network. DEGs were significantly enriched in amoebiasis, vascular smooth
      muscle contraction, and the Wnt and calcium signaling pathways. The expression
      levels of significant DEGs, UCHL1, PDPK1 and PRKACB were validated using RT-qPCR
      analysis. The findings revealed that UCHL1 and PDPK1 were upregulated and PRKACB
      was downregulated in patients with PD when compared with normal healthy controls.
      In conclusion, the results indicate that the significant DEGs, including UCHL1,
      PDPK1 and PRKACB may be associated with the development of PD. In addition, these
      factors may be involved in various signaling pathways, including amoebiasis,
      vascular smooth muscle contraction and the Wnt and calcium signaling pathways.

PMID- 28765972
TI  - The anti-inflammatory effects of Yunnan Baiyao are involved in regulation of the
      phospholipase A2/arachidonic acid metabolites pathways in acute inflammation rat
      model.
AB  - The traditional Chinese medicine Yunnan Baiyao (YNB) has been reported to possess
      anti-inflammatory properties, however its mechanism of action remains unclear. It
      was previously reported that YNB ameliorated depression of arachidonic acid (AA)
      levels in a rat model of collagen-induced arthritis. In the current study, the
      capacity of YNB to ameliorate inflammation was compared in carrageenan-induced
      and AA-induced acute inflammation of the rat paw with celecoxib and mizolastine,
      respectively (n=24 per group). The capacity of YNB to affect the phospholipase A2
      (PLA2)/AA pathway (using reverse transcription-quantitative polymerase chain
      reaction) and release of inflammatory lipid mediators (by ELISA) were
      investigated. Celecoxib ameliorated carrageenan-induced paw edema, and
      mizolastine ameliorated AA-induced rat paw edema. YNB alleviated paw edema and
      inhibited inflammatory cell infiltration in the two models. YNB inhibited
      production of 5-LOX AA metabolite leukotriene B4 (LTB4), and suppressed
      expression of 5-LOX, cytosolic PLA2 (cPLA2), 5-LOX-activating protein, and LTB4
      receptor mRNA in the AA-induced inflammation model (P<0.05). YNB Inhibited the
      production of the COX-2 AA metabolite prostaglandin E2 (PGE2) and suppressed
      expression of COX-2, cPLA2, PGE2 mRNA in the carrageenan-induced inflammation
      mode (P<0.05). Taken together, the data suggest that modulation of COX and LOX
      pathways in AA metabolism represent a novel anti-inflammatory mechanism of YNB.

PMID- 28765973
TI  - Differential expression of B-type natriuretic peptide between left and right
      ventricles, with particular regard to sudden cardiac death.
AB  - The aim of the present study was to investigate the differential expression of B
      type natriuretic peptide (BNP) between the left and right ventricle (RV) in
      sudden cardiac death (SCD). A total of 26 forensic autopsy cases of sudden death
      (survival time <30 min, postmortem interval <48 h or frozen within 6 h following
      death) in the present institute were examined. The cases consisted of acute
      ischemic heart disease (AIHD, n=15) with/without apparent myocardial necrosis as
      a sign of infarction (acute myocardial infarction, n=6; ischemic heart disease,
      IHD, n=9), and arrhythmogenic right ventricular cardiomyopathy (ARVC/D, n=5), in
      addition to traffic accidents and high falls without any pre existing heart
      disease as control (C, total n=6). BNP was investigated in all cases by the
      colloidal gold method, hematoxylin-eosin staining, immunohistochemistry (IHC) and
      the molecular pathological method. The IHC results demonstrated that a positive
      BNP immunostaining was detected in all groups; however, there was no difference
      between different causes of death. Pericardial N-terminal (NT)-proBNP
      concentration was significantly increased in deaths resulting from AIHD and
      ARVC/D compared with control group. The relative quantification of BNP mRNA
      demonstrated that relative expression levels of BNP mRNA were significantly
      increased in the left ventricle (LV) in the AIHD group, and in the RV of the
      ARVC/D group. The relative quantification difference and ratio of BNP mRNA
      between LV and RV demonstrated a significantly greater value in the AIHD group
      compared with control group. BNP mRNA in myocardium and NT-proBNP concentration
      in pericardial fluid were elevated in SCD patients, and left ventricular
      dysfunction predominated in AIHD patients, whereas right ventricular dysfunction
      predominated in ARVC/D patients. The results of the present study suggest the
      possible use of molecular pathology of BNP for the determination of terminal
      cardiac function in SCD and analysis of its fatal mechanism in forensic practice.

PMID- 28765975
TI  - Contrast-enhanced ultrasonography improves the diagnostic specificity for
      gallbladder-confined focal tumors.
AB  - PURPOSE: To investigate the value of contrast-enhanced ultrasonography (CEUS) in
      the differential diagnosis of malignant and benign focal gallbladder diseases
      confined to the gallbladder wall. METHODS: From July 2006 to May 2016, 88
      patients (mean age 48.8 years; age range 18-77 years) were enrolled. All patients
      had focal gallbladder lesions confined to the gallbladder wall according to CEUS
      examination. The conventional ultrasound and CEUS characteristics of the lesions
      were evaluated, and diagnostic performance was evaluated via receiver-operating
      characteristic (ROC) analysis. RESULTS: Multiple logistic regression analysis
      showed that three characteristics, an irregular shape, branched intralesional
      vessels and hypo-enhancement in the late phase, were features indicating a
      malignant gallbladder disease (all P < 0.05). When combining any two of these
      three features, diagnostic specificity improved from 51.5%-77.3% to 92.4% (P <
      0.05 for all), and the area under the ROC (AUROC) curve improved from 0.735-0.874
      to 0.917, without a significant loss of sensitivity. CONCLUSIONS: CEUS features
      have greater specificity than those from conventional US for the differentiation
      of benign and malignant gallbladder diseases confined to the gallbladder wall,
      without a loss of sensitivity.

PMID- 28765974
TI  - Effects of combined general-epidural anesthesia and total intravenous anesthesia
      on cellular immunity and prognosis in patients with non-small cell lung cancer: A
      comparative study.
AB  - The aim of the present study was to investigate the effects of combined general
      epidural anesthesia (CGEA) and total intravenous anesthesia (TIVA) on cellular
      immunity and prognosis in patients with non-small cell lung cancer (NSCLC) in a
      Chinese population. One-hundred and twenty NSCLC patients were randomly divided
      into a TIVA group (n=60) and a CGEA group (n=60) using a random number table. All
      patients underwent video-assisted thoracoscopic surgery for radical resection.
      Blood pressure (BP) and peripheral oxygen saturation (SpO2) were measured. Post
      operative analgesic effects were evaluated with a visual analog scale pain score.
      Flow cytometry was applied to measure T lymphocyte subsets [cluster of
      differentiation (CD)3+, CD4+, CD8+ and CD4+/CD8+] and natural killer cell CD56+.
      A 3-year follow-up was conducted to observe the prognosis. The analgesic effects
      of CGEA were identified to be better than those of TIVA. Compared with the TIVA
      group, the CGEA group demonstrated a shorter time of spontaneous breathing
      recovery, eyes opening, and extubation, lower heart rate, blood pressure and mean
      arterial pressure, and higher SpO2. At 24 and 48 h after surgery, CD3+, CD4+,
      CD4+/CD8+ and CD56+ in the CGEA group were higher than those in the TIVA group.
      At 72 h after surgery, CD3+, CD4+, CD4+/CD8+ in the CGEA group were higher than
      those in the TIVA group. These results indicate that CGEA and TIVA effected
      cellular immunity, and CGEA had a reduced effect on cellular immunity and
      improved postoperative analgesic effects.

PMID- 28765976
TI  - Safety and efficacy of transcatheter embolization with Glubran(r)2 cyanoacrylate
      glue for acute arterial bleeding: a single-center experience with 104 patients.
AB  - PURPOSE: To assess the efficacy and the safety of Glubran(r)2 n-butyl
      cyanoacrylate metacryloxysulfolane (NBCA-MS) transcatheter arterial embolization
      (TAE) for acute arterial bleeding from varied anatomic sites and to evaluate the
      predictive factors associated with clinical success and 30-day mortality.
      METHODS: A retrospective review of consecutive patients who underwent emergent
      NBCA-MS Glubran(r)2 TAE between July 2014 and August 2016 was conducted.
      Variables including age, sex, underlying malignancy, cardiovascular
      comorbidities, coagulation data, systolic blood pressure, and number of red blood
      cells units (RBC) transfused before TAE were collected. Clinical success, 30-day
      mortality, and complication rates were evaluated. Prognostic factors were
      evaluated by uni- and multivariate logistic regression analyses for clinical
      success, and by uni- and bivariate analyses after adjustment by bleeding sites
      for 30-day mortality. RESULTS: 104 patients underwent technically successful
      embolization with bleeding located in muscles (n = 34, 32.7%), digestive tract (n
      = 28, 26.9%), and viscera (n = 42, 40.4%). Clinical success rate was 76% (n = 79)
      and 30-day mortality rate was 21.2% (n = 22). Clinical failure was significantly
      associated with mortality (p < 0.0001). A number of RBC units transfused greater
      than or equal to 3 were associated with poorer clinical success (p = 0.025) and
      higher mortality (p = 0.03). Complications (n = 4, 3.8%) requiring surgery
      occurred only at puncture site. No ischemic complications requiring further
      invasive treatment occurred. Mean TAE treatment time was 4.55 min. CONCLUSIONS:
      NBCA-MS Glubran(r)2 TAE is a fast, effective, and safe treatment for acute
      arterial bleeding whatever the bleeding site.

PMID- 28765977
TI  - The hourglass gallbladder.

PMID- 28765978
TI  - Imaging features of hepatocellular carcinoma compared to intrahepatic
      cholangiocarcinoma and combined tumor on MRI using liver imaging and data system
      (LI-RADS) version 2014.
AB  - PURPOSE: To evaluate the prevalence of major and ancillary imaging features from
      liver imaging reporting and data systems (LI-RADS) version 2014 and their
      interreader agreement when comparing hepatocellular carcinoma (HCC) to
      intrahepatic cholangiocarcinoma (ICC) and combined tumor (cHCC-CC). METHODS: The
      Institutional Review Board approved this HIPAA-compliant retrospective study and
      waived the requirement for patients' informed consent. Patients with resected HCC
      (n = 51), ICC (n = 40), and cHCC-CC (n = 11) and available pre-operative contrast
      enhanced MRI were included from 2000 to 2015. Imaging features and final LI-RADS
      category were evaluated by four radiologists. Imaging features were compared by
      Fisher's exact test and interreader agreements were assessed by kappa statistics.
      RESULTS: None of the features were unique to either HCC or non-HCC. Imaging
      features that were significantly more common among HCC compared to ICC and cHCC
      CC included washout (76%-78% vs. 10%-35%, p < 0.001), capsule (55%-71% vs. 16%
      49%, p < 0.05), and intralesional fat (27%-52% vs. 2%-12%, p < 0.002). Features
      that were more common among ICC and cHCC-CC included peripheral arterial phase
      hyperenhancement (40%-64% vs. 10%-14%, p < 0.001) and progressive central
      enhancement (65%-82% vs. 14%-25%, p < 0.001). The interreader agreement was
      moderate for each of these imaging features (kappa = 0.41-0.55). Moderate
      agreement was also achieved in the assignment of LR-M (kappa = 0.53), with an
      overall sensitivity and specificity for non-HCC malignancy of 86.3% and 78.4%,
      respectively. CONCLUSION: HCC and non-HCC show significant differences in the
      prevalence of imaging features defined by LI-RADS, and are identified by
      radiologists with moderate interreader agreement. Using LI-RADS, radiologists
      also achieved moderate interreader agreement in the assignment of the LR-M
      category.

PMID- 28765979
TI  - Utility of transabdominal ultrasound for surveillance of known pancreatic cystic
      lesions: prospective evaluation with MRI as reference standard.
AB  - OBJECTIVES: To prospectively assess the utility of transabdominal ultrasound in
      surveillance of known pancreatic cystic lesions (PCL) using same day MRI as
      reference standard. METHODS: In an IRB-approved study with written informed
      consent, patients with known PCL underwent pancreas US on same day as
      surveillance MRI. US was performed blinded to same date MRI results. Transverse
      (TR), antero-posterior (AP), cranio-caudal (CC), and longest any plane diameter,
      were measured for each PCL at US and MRI. Visualization was correlated with
      patient (weight, abdominal diameter, thickness of abdominal fat, sex) and cyst
      (location, size, internal complexity) factors. RESULTS: 252 PCLs evaluated in 57
      subjects (39 females; mean age 67 (range 39-86) yrs). Mean maximum PCL diameter
      8.5 (range 2-92) mm. US identified 100% (5/5) of cysts >=3 cm; 92% (12/13) >=2
      and <3 cm; 78% (43/55) >=1 and <2 cm; 35% (27/78) >=5 mm and <1 cm; and 16%
      (16/101) <5 mm. US visualization correlated with PCL location (<0.0001), size (p
      < 0.0001), patient gender (p = 0.005), participation of attending radiologist (p
      = 0.03); inversely with patient weight (p = 0.012) and AP abdominal diameter (p =
      0.01). CONCLUSION: Many PCLs are visualized and accurately measured at follow-up
      with transabdominal ultrasound. Visualization correlates with lesion size,
      location, patient sex, weight, and abdominal diameter.

PMID- 28765980
TI  - The Aboveground Vegetation Type and Underground Soil Property Mediate the
      Divergence of Soil Microbiomes and the Biological Interactions.
AB  - The composition of the soil microbiome is influenced by environmental (abiotic)
      variables and biological interactions (biotic factors). To determine whether the
      aboveground vegetation and soil physicochemical properties were the main
      determinant of beta-diversity and biological interaction of soil microbial
      community, we sampled soils from the temperate coniferous forest and grassland.
      Clustering of operational taxonomic units was conducted using 16S rRNA gene. We
      found that the microbial composition of the rhizospheres, in which root exudates
      influence the microbial environment, show lower alpha-diversity than that of
      nonroot soils. The nonsignificant rhizosphere effect suggested other undetermined
      factors or stochastic processes accounted for microbial diversity in the
      rhizosphere. More significant microbe-microbe interactions were observed in
      forest and rhizosphere soils relative to the grassland soils. The elevated number
      of positive correlations for relative abundances in forest soil implied
      beneficial associations being common among bacteria, in particular within the
      rhizosphere environment. The particular soil properties generated by root
      exudates also alter the physicochemical properties of soil such as K and pH
      value, and might in turn favor the adoption of teamwork-cooperation strategies
      for microbe-microbe interactions, represented as large clusters of positive
      associations among bacterial taxa. Specific biological interactions
      differentiated the microbiomes within forest soils. Thus, the environmental
      selection pressure of aboveground vegetation accounts for differences between
      soil microbiomes while biotic factors are responsible for fine-scale differences
      of the microbial community in forest soils.

PMID- 28765981
TI  - [Anatomic stabilization of chronic lateral instability of the ankle : Gold
      technique].
AB  - OBJECTIVES: Anatomical reconstruction of the lateral ligament complex in the
      ankle. INDICATIONS: Chronic lateral ankle instability. CONTRAINDICATIONS: Severe
      osteoarthritis, obesity, hindfoot varus, general contraindications (infection,
      circulatory disorders, diabetic foot syndrome). SURGICAL TECHNIQUE: Anatomical V
      shaped reconstruction of the lateral ligament complex with half of the peroneus
      brevis tendon and additional retinaculum stabilization. POSTOPERATIVE MANAGEMENT:
      Lower leg orthesis (e. g. protect.CAT Walker, medi GmbH, Bayreuth, Germany) for 6
      weeks. Week 1-2, no weight bearing, no active pro- and supination. Starting in
      week 3-4, begin with partial weight bearing, pain adapted. Starting in week 7,
      free range of motion, begin with progressive training. RESULTS: Between March
      2014 and June 2016, 16 patients (6 female, 10 male) were treated with the above
      named technique. Average age was 32.8 years (range 17.9-57.1 years). Ten patients
      completed the 6- and 12-month follow-ups. None of these 10 patients reported a
      feeling of instability. In the clinical examination, the lateral ligament complex
      was stable. Patients showed a free range of motion at the 12-month follow-up.

PMID- 28765982
TI  - [Words of greeting for the new category rare diseases].

PMID- 28765983
TI  - [Circulatory failure : Out- and inpatient management].
AB  - Circulatory insufficiency is often understood as symptomatic hypotension due to
      various causes. The clinical result of circulatory dysregulation is arterial
      hypotension. The manifestation of hypotension is often divided into chronic and
      acute forms. Chronic hypotension can be distinguished etiopathogenetically into
      primary and secondary hypotension. Acute hypotension is usually equated to
      circulatory shock. While patients with chronic hypotension should be seen
      primarily by their general practitioner, patients with acute hypotension and a
      frequently severe clinical manifestation should be evaluated in the emergency
      department or, if there is a specific cause, directly in the acute clinic.
      Standardization of diagnostic and therapeutic pathways in both out- and inpatient
      care-not only for the management of circulatory weakness-would be an improvement
      not only in regards to patient care, but also with respect to healthcare
      economics.

PMID- 28765984
TI  - [Acute chest pain].
AB  - Patients presenting with acute chest pain are a challenge for attending
      physicians in private practice and specialists for emergency and acute medicine
      in hospitals because a wide spectrum of diagnoses may be the cause, ranging from
      acute myocardial infarction (AMI) to harmless muscular tension. The evaluation of
      patients with acute chest pain follows basic principles independent of the
      setting: A thorough clinical investigation by the responsible physician including
      medical history and physical examination, followed by a 12-channel
      electrocardiogram (ECG) and further focused diagnostics. The decision about
      hospital admission, monitoring and further diagnostic steps depends on the
      estimation of vital risk, the tentative diagnosis and the available diagnostic
      tools. Besides the ECG, laboratory tests (cardiac troponin, copeptin) and cardiac
      imaging (primarily the echocardiography) play a key role. Patients who did not
      necessarily require hospital admission (e. g. after exclusion of AMI) should be
      offered an inpatient or outpatient concept which enables the timely diagnosis and
      potential treatment of all relevant diseases in question. The diagnostic
      strategies need to take into account the pretest probability and for patients
      with confirmed diagnosis of an acute coronary syndrome (ACS), continuous
      monitoring and transfer to an emergency department with integrated chest pain
      unit (CPU) is strongly recommended. In this context, close collaboration between
      the emergency department and the physicians in private practice should be
      established.

PMID- 28765985
TI  - Translational genomics of grain size regulation in wheat.
AB  - KEY MESSAGE: Identifying and mapping grain size candidate genes in the wheat
      genome greatly empowers reverse genetics approaches to improve grain yield
      potential of wheat. Grain size (GS) or grain weight is believed to be a major
      driving force for further improvement of wheat yield. Although the large,
      polyploid genome of wheat poses an obstacle to identifying GS determinants using
      map-based cloning, a translational genomics approach using GS regulators
      identified in the model plants rice and Arabidopsis as candidate genes appears to
      be effective and supports a hypothesis that a conserved genetic network regulates
      GS in rice and wheat. In this review, we summarize the progress in the studies on
      GS in the model plants and wheat and identify 45 GS candidate loci in the wheat
      genome. In silico mapping of these GS loci in the diploid wheat and barley
      genomes showed (1) several gene families amplified in the wheat lineage, (2) a
      significant number of the GS genes located in the proximal regions surrounding
      the centromeres, and (3) more than half of candidate genes to be negative
      regulators, or their expression negatively related by microRNAs. Identifying and
      mapping the wheat GS gene homologs will not only facilitate candidate gene
      analysis, but also open the door to improving wheat yield using reverse genetics
      approaches by mining desired alleles in landraces and wild ancestors and to
      developing novel germplasm by TILLING and genome editing technologies.

PMID- 28765986
TI  - A mathematical model of algae growth in a pelagic-benthic coupled shallow aquatic
      ecosystem.
AB  - A coupled system of ordinary differential equations and partial differential
      equations is proposed to describe the interaction of pelagic algae, benthic algae
      and one essential nutrient in an oligotrophic shallow aquatic ecosystem with
      ample supply of light. The existence and uniqueness of non-negative steady states
      are completely determined for all possible parameter range, and these results
      characterize sharp threshold conditions for the regime shift from extinction to
      coexistence of pelagic and benthic algae. The influence of environmental
      parameters on algal biomass density is also considered, which is an important
      indicator of algal blooms. Our studies suggest that the nutrient recycling from
      loss of algal biomass may be an important factor in the algal blooms process; and
      the presence of benthic algae may limit the pelagic algal biomass density as they
      consume common resources even if the sediment nutrient level is high.

PMID- 28765987
TI  - Anastomosis of the external carotid artery and the V3 segment of the vertebral
      artery (presumed persistent second cervical intersegmental artery) diagnosed by
      CT angiography.
AB  - Congenital anastomosis of the external carotid (ECA) and vertebral (VA) arteries
      is extremely rare. We report a case of right ECA-VA anastomosis diagnosed by
      computed tomography (CT) angiography. The presumed dilated ascending pharyngeal
      artery coursed posteriorly and entered the C1 right transverse foramen. The
      proximal right VA was aplastic, and the C2 right transverse foramen was absent.
      Based on these findings, we diagnosed congenital anastomosis of the ECA and V3
      segment of the VA, which we presumed to represent persistence of the second
      cervical intersegmental artery. Detection of rare variations of the vertebral
      arteries requires careful observation of CT angiography with bone images and
      source images, especially to identify the level of entry into the transverse
      foramen. Correct diagnosis of anastomosis is important when intravascular
      embolization or infusion chemotherapy or surgical ligation of the ECA is planned.

PMID- 28765988
TI  - Scaphoid nonunion: does open reduction, bone grafting and Herbert screw fixation
      justify the treatment?
AB  - PURPOSE: Conventional bone grafting and Herbert screw fixation give satisfactory
      results for scaphoid nonunion; however, vascularized bone grafting has superior
      results, especially in the case of avascular necrosis of proximal fragment.
      Vascularized bone grafting is technically more demanding with small error of
      margin, problems of getting the appropriate graft, fixation and incorporation,
      and requires longer duration for wrist immobilization. METHODS: Forty-five
      patients of scaphoid nonunion were treated by cancellous bone grafting, cortex
      containing graft if required and Herbert screw fixation. Functional outcomes were
      assessed at the latest follow up after surgery (minimum one year after surgery).
      RESULTS: The average pre-operative and post-operative scapho-lunate angle, grip
      strength, flexion-extension movement, radio-ulnar movement, scaphoid index and
      modified mayo score were improved from 49.60 +/- 6.40 degrees  (37-66) to 36.26
      +/- 4.73 degrees  (range 28-46), 20.66 +/- 3.17 kg (15-27) to 31.11 +/- 3.29 kg
      (range 25-40), 78.57 +/- 14.22 degrees  (45-110) to 132.86 +/- 13.90 degrees 
      (100-165), 30.06 +/- 6.06 degrees  (20-44) to 44.95 +/- 6.37 degrees (range 35
      59), 0.66 +/- 0.076 (0.55-0.79) to 0.60 +/- 0.065 (range 0.49-0.73) and 58.66 +/-
      5.24 (50-70) to 84.37 +/- 5.01 (range 75-95), respectively, with P value <0.001.
      Based on modified mayo score, 21 (46.7%) patients had excellent results, 19
      (42.2%) had good results, 4 (8.9%) had fair results and one patient (2.2%) had
      poor results. CONCLUSION: Bone grafting and Herbert screw fixation provides a
      good option for treatment of scaphoid nonunion, especially in the absence of
      avascular necrosis of proximal fragment. More importantly, vascularized bone
      grafting in all scaphoid nonunion may not be necessary and could otherwise have
      been united uneventfully by this technique. However, avascular necrosis of
      proximal fragment must be ruled out pre-operatively as well as intra-operatively.

PMID- 28765989
TI  - Eco-Health linkages: assessing the role of ecosystem goods and services on human
      health using causal criteria analysis.
AB  - OBJECTIVES: In the last decade, we saw an upsurge of studies evaluating the role
      of ecosystem goods and services (EGS) on human health (Eco-Health). Most of this
      work consists of observational research of intermediate processes and few address
      the full pathways from ecosystem to EGS to human health, limiting our ability to
      assess causality. METHODS: We conducted a causal criteria analysis of Eco-Health
      literature using Eco-Evidence, a software tool that helps evaluate evidence of
      cause-effect relationships. We focus on the context of green spaces providing
      "buffering" EGS that may influence disease. RESULTS: We found support for a
      causal linkage between green spaces and all of the EGS tested, and sufficient
      evidence linking EGS to gastro intestinal disease and heat morbidities.
      Inconsistencies were found when assessing the link between EGS to cardiovascular
      and respiratory diseases. Few studies directly link green spaces to health. Those
      that do, support a connection to cardiovascular disease, and heat morbidities,
      but provide inconsistent evidence regarding respiratory illness. CONCLUSIONS: Our
      results help establish an agenda to shape future Eco-Health research and define
      priorities for managing green spaces to provide human health benefits.

PMID- 28765990
TI  - The "Origin-of-Life Reactor" and Reduction of CO2 by H2 in Inorganic
      Precipitates.
AB  - It has been suggested that inorganic membranes were forerunners of organic
      membranes at the origin of life. Such membranes, interposed between alkaline
      fluid in submarine vents and the more acidic Hadean ocean, were thought to house
      inorganic molecular machines. H+ flowed down the pH gradient (DeltapH) from ocean
      to vent through the molecular machines to drive metabolic reactions for early
      life. A set of experiments was performed by Herschy et al. (J Mol Evol 79:213
      227, 2014) who followed earlier work to construct inorganic precipitate membranes
      which, they argued, would be transected by a DeltapH. They supposed that
      inorganic molecular machines might assemble by chance in the precipitate
      membranes, and be capable of using the DeltapH to drive unfavourable reduction of
      CO2 by H2 to formate and formaldehyde. Indeed, these workers detected both of
      these compounds in their origin-of-life reaction vessel and contend this was
      proof of principle for their hypothesis. However, it is shown here by a
      straightforward calculation that the formate produced was only that which reached
      on approach to equilibrium without any driving force from DeltapH. We conclude
      that the reaction was facilitated by isotropic catalysts in the precipitate
      membrane but not by an anisotropic DeltapH-driven molecular machine.

PMID- 28765991
TI  - Ultrasound elastography in tendon pathology: state of the art.
AB  - Elastography assesses the biomechanical and structural properties of tissues by
      measuring their stiffness. Despite promising results, elastography has not yet
      earned its place in the daily practice of musculoskeletal radiologists. The
      purpose of this article is to present and examine the data available to date on
      ultrasound elastography of the tendons through a review of the literature to
      provide musculoskeletal radiologists with an overview that may help them better
      understand and use elastography routinely. The most common techniques in
      ultrasound elastography are described. Then, the aspects of the physiologic and
      pathologic tendon are presented and discussed. One must make this technique one's
      own to better apprehend its contribution to the musculoskeletal imaging field,
      while bearing in mind that further research will be required before admitting
      elastography as a reliable and validated tool able to optimize our daily clinical
      practice.

PMID- 28765992
TI  - Inhibition in movement plan competition: reach trajectories curve away from
      remembered and task-irrelevant present but not from task-irrelevant past visual
      stimuli.
AB  - The current study investigated the role of automatic encoding and maintenance of
      remembered, past, and present visual distractors for reach movement planning. The
      previous research on eye movements showed that saccades curve away from locations
      actively kept in working memory and also from task-irrelevant perceptually
      present visual distractors, but not from task-irrelevant past distractors.
      Curvature away has been associated with an inhibitory mechanism resolving the
      competition between multiple active movement plans. Here, we examined whether
      reach movements underlie a similar inhibitory mechanism and thus show systematic
      modulation of reach trajectories when the location of a previously presented
      distractor has to be (a) maintained in working memory or (b) ignored, or (c) when
      the distractor is perceptually present. Participants performed vertical reach
      movements on a computer monitor from a home to a target location. Distractors
      appeared laterally and near or far from the target (equidistant from central
      fixation). We found that reaches curved away from the distractors located close
      to the target when the distractor location had to be memorized and when it was
      perceptually present, but not when the past distractor had to be ignored. Our
      findings suggest that automatically encoding present distractors and actively
      maintaining the location of past distractors in working memory evoke a similar
      response competition resolved by inhibition, as has been previously shown for
      saccadic eye movements.

PMID- 28765993
TI  - Effects of acute peripheral/central visual field loss on standing balance.
AB  - Vision impairments such as age-related macular degeneration (AMD) and glaucoma
      are among the top risk factors for geriatric falls and falls-related injuries.
      AMD and glaucoma lead to loss of the central and peripheral visual fields,
      respectively. This study utilized a custom contact lens model to occlude the
      peripheral or central visual fields in healthy adults, offering a novel within
      subject approach to improve our understanding of the etiology of balance
      impairments that may lead to an increased fall risk in patients with visual field
      loss. Two dynamic posturography tests, including an adapted version of the
      Sensory Organization Test and a virtual reality environment with the visual scene
      moving sinusoidally, were used to evaluate standing balance. Balance stability
      was quantified by displacement and time-normalized path length of the center of
      pressure. Nine young and eleven older healthy adults wore visual field occluding
      contact lenses during posturography assessments to compare the effects of acute
      central and peripheral visual field occlusion. The results found that visual
      field occlusion had greater impact on older adults than young adults,
      specifically when proprioceptive cues are unreliable. Furthermore, the results
      suggest that both central and peripheral visions are important in postural
      control; however, peripheral vision may be more sensitive to movement in the
      environment.

PMID- 28765994
TI  - Modulation of financial deprivation on deception and its neural correlates.
AB  - Deception is a universal phenomenon in human society and plays an important role
      in everyday life. Previous studies have revealed that people might have an
      internalized moral norm of keeping honest and the deceptive behavior was reliably
      correlated with activation in executive brain regions of prefrontal cortices to
      over-ride intuitive honest responses. Using functional magnetic resonance
      imaging, this study sought to investigate how financial position modulated the
      neural responses during deceptive decision. Twenty-one participants were scanned
      when they played a series of adapted Dictator Game with different partners after
      a ball-guess game. Specifically, participants gained or lost money in the ball
      guess game, and had opportunities to get more financial gains through cheating in
      the following adapted Dictator Game. Behavioral results indicated that
      participants did not cheat to the full extent; instead they were more likely to
      lie after losing money compared with gaining money. At the neural level, weaker
      activities in the dorsolateral prefrontal cortices were observed when
      participants lied after losing money than gaining money. Together, our data
      indicated that, people really had an internalized norm of keeping honest, but it
      would be lenient when people feel financial deprivation. And suppressing the
      truthful response originating from moral norm of keeping honest was associated
      with increased level of activation in the dorsolateral prefrontal cortices, but
      this association became weaker when people were under financial deprivation.

PMID- 28765995
TI  - Quantification of myelin in children using multiparametric quantitative MRI: a
      pilot study.
AB  - PURPOSE: The purpose of this study was to evaluate the usefulness of
      multiparametric quantitative MRI for myelination quantification in children.
      METHODS: We examined 22 children (age 0-14 years) with multiparametric
      quantitative MRI. The total volume of myelin partial volume (Msum), the
      percentage of Msum within the whole brain parenchyma (Mbpv), and the percentage
      of Msum within the intracranial volume (Micv) were obtained. Four developmental
      models of myelin maturation (the logarithmic, logistic, Gompertz, and modified
      Gompertz models) were examined to find the most representative model of the three
      parameters. We acquired myelin partial volume values in different brain regions
      and assessed the goodness of fit for the models. RESULTS: The ranges of Msum,
      Mbpv, and Micv were 0.8-160.9 ml, 0.2-13%, and 0.0-11.6%, respectively. The
      Gompertz model was the best fit for the three parameters. For developmental model
      analysis of myelin partial volume in each brain region, the Gompertz model was
      the best-fit model for pons (R 2 = 74.6%), middle cerebeller peduncle (R 2 =
      76.4%), putamen (R2 = 95.8%), and centrum semiovale (R 2 = 77.7%). The logistic
      model was the best-fit model for the genu and splenium of the corpus callosum (R
      2 = 79.7-93.6%), thalamus (R 2 = 81.7%), and frontal, parietal, temporal, and
      occipital white matter (R 2 = 92.5-96.5%). CONCLUSIONS: Multiparametric
      quantitative MRI depicts the normal developmental pattern of myelination in
      children. It is a potential tool for research studies on pediatric brain
      development evaluation.

PMID- 28765996
TI  - Non-central peripherally inserted central catheters in neonatal intensive care:
      complication rates and longevity of catheters relative to tip position.
AB  - BACKGROUND: Peripherally inserted central catheters (PICCs) represent a mainstay
      of intravascular access in the neonatal intensive care setting when long-term
      vascular access is needed. Ideally, PICCs should be inserted and maintained in a
      central position with the tip ending in the superior or inferior vena cava. This
      is not always achievable, and sometimes the tip remains in a peripheral location.
      Higher complication rates have been reported with non-central PICCs; however
      these findings have not been confirmed in a solely neonatal series and PICCs with
      tips in peripheral veins have not been studied. OBJECTIVE: To compare
      complication rates and length of catheter duration related to PICC position in
      neonates. MATERIALS AND METHODS: We conducted a retrospective analysis of all
      PICCs inserted in term and preterm infants in a tertiary neonatal intensive care
      unit between May 2007 and December 2009. A single pediatric radiologist
      reinterpreted the catheter tip site on initial anteroposterior (AP) chest
      radiographs and categorized sites as central (superior vena cava, inferior vena
      cava, brachiocephalic vein), intermediate (subclavian, axillary, common or
      external iliac veins), or peripheral (veins peripheral to axillary or external
      iliac veins). We analyzed complication rates and length of catheter duration
      among the three categories. RESULTS: We collected data on a total of 176 PICCs.
      Infants with PICCs in a central location had a significantly lower complication
      rate (18/97, 19%) than those with the PICC tip in an intermediate (24/64, 38%) or
      peripheral (9/15, 60%) locations (P=0.0003). Length of catheter duration was
      noted to be longest with central, intermediate with intermediate, and shortest
      with peripheral PICC tip locations (17.7+/-14.8 days for central vs. 11.4+/-10.7
      days for intermediate vs. 5.4+/-2.5 days for peripheral, P=0.0003). CONCLUSION: A
      central location is ideal for the tip of a PICC. When this is not achievable, an
      intermediate location is preferable to a more peripheral position.

PMID- 28765997
TI  - Changes in femoral head size and growth rate in young children with severe
      developmental dysplasia of the hip.
AB  - BACKGROUND: Developmental dysplasia of the hip (DDH) is known to result in
      smaller femoral head size in toddlers; however, alterations in femoral head size
      and growth have not been documented in infants. OBJECTIVE: To determine with
      ultrasound (US) whether femoral head size and growth are altered in infants
      (younger than 1 year of age) with severe DDH. MATERIALS AND METHODS: We
      identified all patients at our tertiary care children's hospital from 2002 to
      2014 who underwent US for DDH. We included studies with at least one hip with
      severe DDH, defined as <25% coverage of the femoral head, and excluded
      teratological DDH. We constructed a control group of randomized patients with
      normal US studies. Two pediatric radiologists blinded to diagnosis measured
      bilateral femoral head diameter. Inter-reader variability and femoral head
      diameter difference between dislocated and contralateral normal femoral heads
      were evaluated. Mean femoral head diameters were compared across types of hip
      joint; femoral head growth rates per month were calculated. RESULTS: Thirty-seven
      children with DDH (28 female) were identified (median age: 33 days). The control
      group contained 75 children (47 female) with a median age of 47 days. Fifty-three
      of the 74 hips in the study group had severe DDH. Twenty-four children with DDH
      had completely dislocated hips (nine bilateral, five with contralateral severe
      subluxations). Thirteen other children had severe subluxation, two bilaterally.
      There was good inter-reader agreement in the normal femoral head group and
      moderate agreement in the severe DDH group. In the study group, severe DDH
      femoral head diameter was significantly smaller than their contralateral normal
      hip. Severe DDH femoral head diameter was significantly smaller than normal
      femoral head diameter in the control group. The severe DDH femoral head growth
      rate was slightly less but not significantly slower than normal femoral head
      growth rate in the study group. CONCLUSION: On US during infancy, femoral head
      size is significantly reduced in severe cases of DDH.

PMID- 28765999
TI  - A rare case of thymoma first detected on gallium-68 PSMA PET/CT.

PMID- 28766000
TI  - [Pediatric brain tumors].
AB  - Brain tumors differ between children and adults both in histology and
      localization. Malignant gliomas and meningiomas predominate in adults while
      medulloblastomas and low-grade astrocytomas are the most frequent brain tumors in
      children. More than one half (50-70%) of pediatric brain tumors have an
      infratentorial location but only approximately 30% in adults. Brain tumors can be
      recognized in sonography, cranial computed tomography (CCT) and magnetic
      resonance imaging (MRI) by their space-consuming character and by their divergent
      density and intensity in comparison to normal brain parenchyma. They can grow
      extrusively, even infiltrate the parenchyma or originate from it. Besides
      clinical symptoms and diagnostics this article describes the most common
      pediatric brain tumors, i.e. astrocytoma, medulloblastoma, brainstem glioma,
      craniopharyngioma, neurofibromatosis and ganglioglioma. The most important
      imaging criteria are outlined.

PMID- 28766001
TI  - Dynamic contrast-enhanced magnetic resonance imaging parameters correlate with
      advanced revised-ISS and angiopoietin-1/angiopoietin-2 ratio in patients with
      multiple myeloma.
AB  - The aim of the study was to assess the value of dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) in patients with newly diagnosed multiple
      myeloma (MM) who were treated with novel anti-myeloma agents. We studied 60
      previously untreated MM patients at diagnosis, 14 with smoldering MM (SMM) and 5
      with MGUS. All patients underwent MRI of the thoracolumbar spine and pelvis
      before the administration of any kind of therapy, and DCE-MRI was performed. The
      MRI perfusion parameters evaluated were wash-in (WIN), washout (WOUT), time-to
      peak (TTPK), time-to-maximum slope (TMSP), and the WIN/TMSP ratio. The following
      serum levels of angiogenic cytokines were measured on the day of MRI: VEGF,
      angiogenin (Ang), angiopoietin-1 (Angp-1), and -2 (Angp-2). Symptomatic MM
      patients had increased WIN compared to SMM (p < 0.05) and MGUS patients (p =
      0.001). TTPK was decreased, and WIN/TMSP was increased in both symptomatic and
      SMM patients compared to MGUS patients (p < 0.05). Symptomatic MM patients had
      decreased TMSP compared to MGUS patients. The Angp-1/Angp-2 ratio was reduced in
      symptomatic MM compared to SMM (p = 0.017) and MGUS patients (p < 0.001). TTPK
      correlated with Angp-1/Angp-2 ratio and importantly with R-ISS. Patients with R
      ISS-3 had lower TTPK median value (23 s, range 18-29 s) compared to patients with
      R-ISS-2 (48 s, range 27-68 s) and patients with R-ISS-1 MM (54 s, range 42-76 s;
      p ANOVA = 0.01). A subset of patients with low TTPK (lower quartile) had shorter
      time to progression compared to all other patients. These data suggest that
      certain DCE-MRI parameters correlate with R-ISS and adverse prognostic features
      of angiogenesis, such as the ratio of Angp-1/Angp-2.

PMID- 28765998
TI  - Pearls and pitfalls in clinical interpretation of prostate-specific membrane
      antigen (PSMA)-targeted PET imaging.
AB  - BACKGROUND: The rapidly expanding clinical adaptation of prostate-specific
      membrane antigen (PSMA)-targeted PET imaging in the evaluation of patients with
      prostate cancer has placed an increasing onus on understanding both the potential
      pearls of interpretation as well as limitations of this new technique. As with
      any new molecular imaging modality, accurate characterization of abnormalities on
      PSMA-targeted PET imaging can be accomplished only if one is aware of the normal
      distribution pattern, physiological variants of radiotracer uptake, and potential
      sources of false-positive and false-negative imaging findings. In recent years, a
      growing number of reports have come to light describing incidental non-prostatic
      benign or malignant pathologies with high uptake on PSMA-targeted PET imaging. In
      this review, we have summarized the published literature regarding the potential
      pearls and technical and interpretive pitfalls of this imaging modality.
      Knowledge of these limitations can increase the confidence of interpreting
      physicians and thus improve patient care. CONCLUSIONS: As PSMA-targeted PET is
      expected to be evaluated in larger prospective trials, the dissemination of
      potential diagnostic pitfalls and the biologic underpinning of those findings
      will be of increased importance.

PMID- 28766002
TI  - Similar survival outcomes in patients with biclonal versus monoclonal myeloma: a
      multi-institutional matched case-control study.
AB  - Multiple myeloma is a plasma cell malignancy characterized by clonal
      proliferation of plasma cells in the bone marrow and associated organ damage.
      Usually, patients with myeloma present with a single monoclonal protein in serum
      and/or urine constituted by one heavy chain and one light chain. In less than 5%
      of the patients, more than one monoclonal protein can be identified. The aim of
      our retrospective multicenter matched case-control study was to describe the
      characteristics of cases with biclonal myeloma and compare them against a control
      group of monoclonal myeloma patients matched by age, sex, and year of diagnosis.
      A total of 50 previously untreated cases with biclonal myeloma and 50 matched
      controls with monoclonal myeloma were included in this study. The controls were
      matched (1:1) for age, sex, year of diagnosis, and participating center. There
      were no differences in the rates of anemia (52 vs. 59%; p = 0.52), renal
      dysfunction (36 vs. 34%; p = 0.83), hypercalcemia (9 vs. 16%; p = 0.28), or
      presence of lytic lesions (23 vs. 16%; p = 0.38) between groups. Similarly, there
      was no difference in the rates of overall response to therapy (85 vs. 90%; p =
      0.88) or survival rates of cases with biclonal myeloma and controls with
      monoclonal myeloma (4-year survival 72 vs. 76%; p = 0.23). Results of our study
      suggest that patients with biclonal myeloma have similar response and survival
      rates than patients with monoclonal myeloma.

PMID- 28766003
TI  - [Editorial - plastic reconstructive genital interventions].

PMID- 28766004
TI  - [Psychosocial stress in patients with prostate cancer : Experiences by using
      psychooncological screening questionnaires].
AB  - BACKGROUND: Prostate cancer is the most common malignancy in men and accounts for
      most surgical procedures in uro-oncology. Stressful sequelae of radical
      prostatectomy are incontinence and erectile dysfunction. Hormone ablation and
      radiation therapy are also known stressors. Mental stress has a low prevalence
      compared to other tumor entities. It is highly probable that there is an
      underexpression of verbally reported emotional experiences. Therefore, a low
      threshold access to psycho-oncological services and accurate identification of
      patients with mental comorbidities is important. The aim of this study was to
      identify the distress level with clarification of the stress in patients with
      prostate cancer. MATERIALS AND METHODS: Prospective evaluation of prostate cancer
      patients (n = 81, mean age 69 years) with regard to stress level, stress factors
      and the need for care using the Distress Thermometer, a standardized ultrashort
      stress-screening questionnaire. RESULTS: The mean stress level was 4.4 points. In
      total, 56% of patients indicated a stress level >=5, i. e. a clinically relevant
      psychological burden was indicated. Main stressors were sexual problems (35%),
      reduced mobility (30%), pain (27.5%), tingling paresthesia (26%) and worries
      (26%). CONCLUSION: The psychological burden of prostate cancer patients is not as
      high as in other solid organ malignancies. However, some patients have a
      significantly increased psychosocial stress level. Identifying this subgroup and
      clarifying the correlation with specific stress and risk factors are important
      tasks of clinical care.

PMID- 28766005
TI  - [What is the current status of shock wave lithotripsy?]
AB  - BACKGROUND: Shock wave lithotripsy (SWL) became the therapy of choice for the
      majority of patients with urolithiasis early after its introduction in the early
      1980s. Since then, SWL remains the only noninvasive therapy modality for the
      treatment of urinary stones. Although lithotripters became more versatile and
      affordable-making them available worldwide-indications for SWL have shifted as
      well. In most western countries, endoscopic techniques took the lead in stone
      therapy due to high (early) stone-free and better reimbursement rates.
      Notwithstanding SWL remains the first-line therapy for most intrarenal and many
      ureteral stones. PURPOSE: This contemporary review illuminates technical aspects
      and improvements of lithotripsy over recent years in context with the current
      guideline recommendations. RESULTS: Technical advances in lithotripsy such as
      shock wave generation, focusing, coupling, stone localization and modifications
      in therapy regimens are reviewed and presented. CONCLUSIONS: Urologists are
      recommended to carefully select the appropriate therapy modality for a patient
      with urolithiasis. A more comprehensive understanding of the physics of shock
      waves could lead to much better results, thus, endorsing SWL as first-line
      therapy for urolithiasis instead of contemporary endourology treatment options.

PMID- 28766006
TI  - Tissue-Level Cardiac Electrophysiology Studied in Murine Myocardium Using a
      Microelectrode Array: Autonomic and Thermal Modulation.
AB  - Cardiac electrophysiology is regulated by the autonomic nervous system, and this
      has both pathophysiological, and possibly therapeutic importance. Furthermore,
      chamber differences in electrophysiology exist between atria and ventricles, yet
      there have been few direct comparisons. There is substantial literature on ion
      channel modulation at the single-cell level but less work on how this affects
      tissue-level parameters. We used a microelectrode array system to explore these
      issues using murine atrial and ventricular tissue slices. Activation time,
      conduction velocity and repolarisation were measured, and their modulation by
      temperature and pharmacological autonomic agonists were assessed. The system
      recorded reliable measurements under control conditions in the absence of
      drug/thermal challenge, and significant baseline differences were found in
      chamber electrophysiology. The sodium channel blocker mexiletine, produced large
      magnitude changes in all three measured parameters. Carbachol and isoprenaline
      induced differing effects in atria and ventricles, whereas temperature produced
      similar effects on activation and repolarisation.

PMID- 28766007
TI  - Multicentric Chordoma : An Uncommon and Incompletely Understood Presentation.

PMID- 28766009
TI  - Erratum to: Managing the genomic revolution in cancer diagnostics.

PMID- 28766008
TI  - Concurrent paclitaxel, capecitabine, mitomycin C and pelvic radiation therapy for
      patients with squamous cell anal carcinoma.
AB  - PURPOSE: The goals of this study were to assess safety and efficacy of triplet
      chemoradiotherapy (CRT) with paclitaxel for squamous cell anal carcinoma (SCAC).
      METHODS: Patients with stage I-IIIB SCAC were enrolled and received 52-58 Gy
      intensity-modulated radiotherapy (IMRT) (with dose based on the T stage) in
      consecutive daily 1.8-2.2 Gy fractions. The concurrent chemotherapy consisted of
      paclitaxel 45 mg/m2 days 3, 10, 17, 24, 31, capecitabine 625 mg/m2 bid on
      treatment days and mitomycin C 10 g/m2 on day 1. Primary endpoints were complete
      clinical response at 26 weeks and protocol compliance; secondary endpoints
      included toxicity, overall survival (OS) and progression-free survival (PFS).
      RESULTS: Thirty-eight patients were enrolled. The percentage of patients with
      stage I, II, IIIA, and IIIB disease were 1 (2.6%), 5 (13.2%), 15 (39.5%), and 17
      (44.7%), respectively. 32 patients (84.2%) completed CRT without significant
      alterations. Grade 3-4 toxicity occurred in 23 (60.5%) patients. 33 (86.8%)
      patients had complete clinical response at 26 weeks. Median follow-up was 25.6
      months. Seven (18.4%) patients experienced disease progression: four patients had
      residual tumor after CRT, 2 patients developed distant metastases and 1 patient
      developed a local recurrence 12 months after CRT. Two-year OS was 93.6%, 2-year
      PFS was 83.9%. CONCLUSIONS: Investigated treatment scheme is feasible despite
      high toxicity profile, and may be beneficial for patients with advanced SCAC.
      Further research is warranted.

PMID- 28766010
TI  - Evaluation of the budding and depth of invasion (BD) model in oral tongue cancer
      biopsies.
AB  - It is of great clinical importance to identify simple prognostic markers from
      preoperative biopsies that could guide treatment planning. Here, we compared
      tumor budding (B), depth of invasion (D), and the combined scores (i.e., budding
      and depth of invasion (BD) histopathologic model) in preoperative biopsies and
      the corresponding postoperative specimens of oral tongue squamous cell carcinoma
      (OTSCC). Tumor budding and depth of invasion were evaluated in the pre- and
      postoperative samples from 100 patients treated for OTSCC. Sensitivity and
      specificity statistics were used. Our results showed statistically significant (P
      < 0.001) relationship between pre- and postoperative BD scores. There was an
      agreement between the pre- and postoperative BD model scores in 83 cases (83%)
      with 57.1% sensitivity (95% CI 39.4 to 73.7%) and 96.9% specificity (95% CI 89.3
      to 99.6%). Our findings suggest that the BD model, analyzed from representative
      biopsies, could be used for the treatment planning of OTSCC.

PMID- 28766011
TI  - RNAi screen identifies essential regulators of human brain metastasis-initiating
      cells.
AB  - Brain metastases (BM) are the most common brain tumor in adults and are a leading
      cause of cancer mortality. Metastatic lesions contain subclones derived from
      their primary lesion, yet their functional characterization is limited by a
      paucity of preclinical models accurately recapitulating the metastatic cascade,
      emphasizing the need for a novel approach to BM and their treatment. We
      identified a unique subset of stem-like cells from primary human patient brain
      metastases, termed brain metastasis-initiating cells (BMICs). We now establish a
      BMIC patient-derived xenotransplantation (PDXT) model as an investigative tool to
      comprehensively interrogate human BM. Using both in vitro and in vivo RNA
      interference screens of these BMIC models, we identified SPOCK1 and TWIST2 as
      essential BMIC regulators. SPOCK1 in particular is a novel regulator of BMIC self
      renewal, modulating tumor initiation and metastasis from the lung to the brain. A
      prospective cohort of primary lung cancer specimens showed that SPOCK1 was
      overexpressed only in patients who ultimately developed BM. Protein-protein
      interaction network mapping between SPOCK1 and TWIST2 identified novel pathway
      interactors with significant prognostic value in lung cancer patients. Of these
      genes, INHBA, a TGF-beta ligand found mutated in lung adenocarcinoma, showed
      reduced expression in BMICs with knockdown of SPOCK1. In conclusion, we have
      developed a useful preclinical model of BM, which has served to identify novel
      putative BMIC regulators, presenting potential therapeutic targets that block the
      metastatic process, and transform a uniformly fatal systemic disease into a
      locally controlled and eminently more treatable one.

PMID- 28766012
TI  - Organizing pneumonia and occupational and environmental risk factors: a case
      control study.
AB  - OBJECTIVES: A single-center case-control study was carried out to investigate the
      relationship between occupational and environmental exposure and organizing
      pneumonia (OP). METHODS: Thirty-seven cases of OP, including 25 cases of
      cryptogenic OP, and 111 controls were included. Occupational exposure was
      assessed retrospectively by an industrial hygienist and an occupational
      physician, through semi-quantitative estimates of exposure. An exposure score was
      calculated for each subject, based on probability, intensity, daily frequency,
      and duration of exposure for each period of employment. The final cumulative
      exposure score was obtained by summing exposure scores for all periods of
      employment. RESULTS: Significant associations with all-cause OP were observed for
      exposure to tetrachloroethylene (OR 13.33, CI 95% 1.44-123.5) and silica (OR
      6.61, CI 95% 1.16-37.71). A significant association with cryptogenic OP was
      observed only for tetrachloroethylene (OR 31.6, CI 95% 1.64-610.8). No
      associations were found for environmental exposure. CONCLUSION: Despite its low
      statistical power, this work suggests that occupational risk factors could be
      involved in OP.

PMID- 28766013
TI  - Metal arc welding and the risk of skin cancer.
AB  - OBJECTIVES: Arc welding produces the full spectrum of ultraviolet radiation and
      may be a contributory cause of skin cancer; however, there has been little
      research into this occupational hazard. The aim of this study is to explore if
      metal arc welding increases the risk of malignant melanoma and/or basal cell
      carcinoma (BCC) and squamous cell carcinoma (SCC) on skin areas which may
      possibly be exposed (neck, head, and upper extremities). METHOD: A Danish
      national company-based historic cohort of 4333 male metal arc welders was
      followed from 1987 through 2012 to identify the risk of skin cancer. An external
      reference group was established including all Danish skilled and unskilled male
      workers with similar age distribution. Occupational histories were gathered by
      questionnaires in 1986 and information about skin cancer diagnoses [BCC, SCC,
      cutaneous malignant melanoma (CMM), and precancerous conditions, actinic
      keratosis (AK)] were gathered from the Danish Cancer Registry supplemented by the
      data from the Danish Pathology Register. Hazard ratios (HRs) were calculated in
      the follow-up period from 1987 until 2012 using Cox regression analysis and
      adjusted for baseline data regarding age and social group. RESULTS: The adjusted
      HR and 95% confidence interval (CI) for skin cancer (all types) were 0.99 (CI
      0.94-1.04) for welders. The adjusted HR for AK and BCC located only at neck was
      2.49 (CI 1.03-5.99) for welders exposed >20 years (n = 5) and 2.46 (CI 1.02
      5.94), respectively, for welders exposed >30 years (n = 5). No statistically
      significant difference was observed for SCC. The risk of CMM at the neck was also
      significantly elevated after 30 years of welding, but this is based upon only one
      exposed case. CONCLUSION: This study indicates that long-term exposure to metal
      arc welding may be related to increased risk of BCC and AK located exclusively at
      the neck. The study provides no support for the hypothesis that welding exposure
      increases the risk for skin cancer at other locations.

PMID- 28766014
TI  - High-temperature promotion of callus formation requires the BIN2-ARF-LBD axis in
      Arabidopsis.
AB  - MAIN CONCLUSION: The auxin-brassinosteroid interaction involving the BIN2-ARF-LBD
      axis plays a key role in temperature-dependent callus formation in Arabidopsis.
      An extensive web of multiple hormone signaling pathways underlies callus
      formation. Here, we report that a brassinosteroid (BR) signaling component, BR
      INSENSITIVE 2 (BIN2), positively regulates callus formation. The BIN2 kinase
      promotes transcriptional activities of AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19
      and subsequently activates expression of LATERAL ORGAN BOUNDARIES-DOMAIN 16
      (LBD16) and LBD29 during callus formation. Consistently, the BIN2 activity is
      dependent on ARFs in the control of callus formation. Notably, this auxin-BR
      interaction is particularly relevant in temperature-dependent callus formation.
      Misexpression of BIN2 and ARFs resulted in the temperature insensitivity of
      callus formation. These results indicate that the BIN2-ARF-LBD axis plays a key
      role in temperature-dependent callus formation in Arabidopsis.

PMID- 28766015
TI  - Reply to Letter to the Editor "Maternally inherited diabetes and deafness is a
      mitochondrial multiorgan disorder syndrome (MIMODS)".

PMID- 28766016
TI  - Transarterial chemoembolization with miriplatin vs. epirubicin for unresectable
      hepatocellular carcinoma: a phase III randomized trial.
AB  - BACKGROUND: This prospective study investigated the superiority of transarterial
      chemoembolization (TACE) with miriplatin over TACE with epirubicin regarding
      overall survival (OS) in patients with unresectable hepatocellular carcinoma
      (HCC). METHODS: Patients with unresectable HCC were randomized 1:1 to receive
      TACE with miriplatin or epirubicin in lipiodol. The primary endpoint was OS;
      secondary endpoints were percentages of patients who achieved treatment effect
      (TE) 4 (100% necrotizing effect or tumor reduction), duration of time to TACE
      failure, and adverse events (AEs). OS was compared using a stratified log-rank
      test adjusted for clinical stage, Child-Pugh class, and institution. RESULTS: Of
      257 patients enrolled from August 2008 to August 2010, 247 were analyzed for
      efficacy and toxicity (miriplatin, n = 124; epirubicin, n = 123). Baseline
      characteristics were well balanced between the two groups. Median OS times were
      1111 days for miriplatin and 1127 days for epirubicin (adjusted hazard ratio
      1.01, 95% confidence interval 0.73-1.40, P = 0.946). TE4 rates were 44.4% for
      miriplatin and 37.4% for epirubicin. Median times to TACE failure were 365.5 days
      for miriplatin and 414.0 days for epirubicin. AEs of grade 3 or higher, including
      elevated aspartate aminotransferase (miriplatin, 39.5%; epirubicin, 57.7%) and
      elevated alanine aminotransferase (miriplatin, 31.5%; epirubicin, 53.7%), were
      less frequent in the miriplatin than the epirubicin group. CONCLUSIONS: OS after
      TACE with miriplatin was not superior to that after TACE with epirubicin;
      however, hepatic AEs were less frequent with miriplatin. CLINICAL TRIAL
      REGISTRATION: JapicCTI-080632.

PMID- 28766018
TI  - S2-AI screw placement with the aide of electronic conductivity device monitoring:
      a retrospective analysis.
AB  - STUDY DESIGN: A retrospective analysis of two consecutive patients who underwent
      a novel surgical technique. OBJECTIVE: A report of a novel surgical technique
      utilizing an electronic conductivity device guidance to aide placement of S2-Alar
      Iliac (S2-AI) instrumentation. Electronic conductivity guidance for
      instrumentation of the thoracolumbar spine is an accepted means of improving
      intraoperative accuracy. Although commercially available for percutaneous
      techniques, there is a paucity of literature regarding its use. Percutaneous
      implantation of S2-AI screws has been previously described as another technique
      surgeons can avail, primarily employing fluoroscopy as a means of intraoperative
      feedback. We describe a novel technique that utilizes electronic conductivity as
      an added feedback measure to increase accuracy of percutaneous S2-AI fixation.
      METHODS: Two patients were treated by the senior author (FAS) who underwent
      surgery employing S2-AI fixation utilizing an electronic conductivity device
      (Pediguard cannulated probe, Spineguard, Paris, France). The surgical technique,
      case illustrations, and radiographic outcomes are discussed. RESULTS: Stable and
      accurate fixation was attained in both patients. There were no peri-operative
      complications related to hardware placement. CONCLUSION: To the authors'
      knowledge, this is the first reported literature combining S2-AI screws with
      electronic conductivity for immediate intraoperative feedback. This technique has
      the opportunity to provide surgeons with increased accuracy for placement of S2
      AI screws while improving overall radiation safety. This feedback can be
      particularly helpful when surgeons are learning new techniques such as placement
      of S2AI screws.

PMID- 28766017
TI  - PMK-1 p38 MAPK promotes cadmium stress resistance, the expression of SKN-1/Nrf
      and DAF-16 target genes, and protein biosynthesis in Caenorhabditis elegans.
AB  - The mechanisms of cadmium (Cd) resistance are complex and not sufficiently
      understood. The present study, therefore, aimed at assessing the roles of
      important components of stress-signaling pathways and of ABC transporters under
      severe Cd stress in Caenorhabditis elegans. Survival assays on mutant and control
      animals revealed a significant promotion of Cd resistance by the PMK-1 p38 MAP
      kinase, the transcription factor DAF-16/FoxO, and the ABC transporter MRP-1.
      Transcriptome profiling by RNA-Seq on wild type and a pmk-1 mutant under control
      and Cd stress conditions revealed, inter alia, a PMK-1-dependent promotion of
      gene expression for the translational machinery. PMK-1 also promoted the
      expression of target genes of the transcription factors SKN-1/Nrf and DAF-16 in
      Cd-stressed animals, which included genes for molecular chaperones or immune
      proteins. Gene expression studies by qRT-PCR confirmed the positive effects of
      PMK-1 on DAF-16 activity under Cd stress and revealed negative effects of DAF-16
      on the expression of genes for MRP-1 and DAF-15/raptor. Additional studies on pmk
      1 RNAi-treated wild type and mutant strains provided further information on the
      effects of PMK-1 on SKN-1 and DAF-16, which resulted in a model of these
      relationships. The results of this study demonstrate a central role of PMK-1 for
      the processing of cellular responses to abiotic and biotic stressors, with the
      promoting effects of PMK-1 on Cd resistance mostly mediated by the transcription
      factors SKN-1 and DAF-16.

PMID- 28766019
TI  - A retrospective imaging study of surgical outcomes and range of motion in
      patients with cervical ossification of the posterior longitudinal ligament.
AB  - PURPOSE: The K line was introduced in a previous study, but did not include the
      cervical range of motion (ROM) as a parameter for evaluating surgical outcomes
      for patients with cervical ossification of the posterior longitudinal ligament
      (OPLL), and few reports have used both the K line and X-ray evaluations of the
      cervical ROM to describe the surgical outcomes in such patients. METHODS: Double
      door C2-C7 or C3-C7 laminoplasty was performed in 100 patients with cervical OPLL
      who were classified according to the K line [86 patients, K line (+) and 14
      patients, K line (-)]. Preoperative and 1-year postoperative Japanese Orthopedic
      Association (JOA) scores were used to evaluate recovery rates. Preoperative and
      postoperative C2-C7 lordotic angles were measured using the Cobb method. In
      addition, preoperative and postoperative sagittal alignments in flexion and
      extension were studied, and the flexion values were calculated by subtracting the
      preoperative and postoperative flexion ROM from extension ROM. RESULTS: The mean
      JOA scores recovery rate were 57.3% in the K line (+) and 37.7% in the K line (-)
      groups (p < 0.05), and the respective corresponding mean postoperative C2-C7
      lordotic angles were 9.1 degrees  and -3.4 degrees  (p < 0.001). In the K line
      (+) group, the JOA score recovery rate for a postoperative flexion value >0 was
      significantly lower than that for a postoperative flexion value <=0 (p < 0.01),
      and the mean JOA score recovery rate worsened with an increased signal intensity
      on 1-year postoperative magnetic resonance imaging. CONCLUSIONS: K line (+)
      patients exhibited sufficient neurological improvement after laminoplasty.
      However, even patients in this group had a low JOA score recovery rate if the
      postoperative flexion value was >0 and the 1-year postoperative increased signal
      intensity grade was 2 or 3.

PMID- 28766020
TI  - Prognostic factors in critically ill patients with hematological malignancy
      admitted to the general intensive care unit: a single-center experience in Japan.
AB  - PURPOSE: This study aims to identify prognostic factors related to short-term and
      long-term outcomes of patients with hematological malignancy (HM) admitted to the
      intensive care unit (ICU) in Japan during ICU stay and after discharge from ICU.
      METHODS: We conducted a retrospective, observational study of 169 patients with
      HM admitted to the general ICU from January 2009 to December 2016. We examined
      prognostic factors affecting outcome during ICU stay and at 180 days after ICU
      discharge using logistic regression analysis. RESULTS: During ICU stay, 57
      patients (33.7%) died. Invasive mechanical ventilation (OR 8.96, 95% CI 3.67
      21.9; P < 0.001, the same hereinafter), the Sequential Organ Failure Assessment
      (SOFA) score within the first 24 h of ICU admission (1.25, 1.11-1.40; P < 0.001),
      and malignant lymphoma (0.30, 0.11-0.78; P = 0.014) were detected as factors
      associated with ICU outcome. Of 112 ICU survivors, 46 (41.1%) died within 180
      days after ICU discharge. Duration of ICU stay (1.07, 1.01-1.13; P = 0.027) and
      the SOFA score at ICU discharge (1.24, 1.04-1.48; P = 0.016) were related to poor
      outcome at 180 days after ICU discharge. CONCLUSIONS: In critically ill patients
      with HM, the use of invasive mechanical ventilation, a high SOFA score within the
      first 24 h of ICU admission, and malignant lymphoma as primary HM affected short
      term ICU outcome. Increased duration of ICU stay and SOFA score at ICU discharge
      influenced long-term outcome at 180 days after ICU discharge.

PMID- 28766021
TI  - Acute kidney injury after pediatric liver transplantation: incidence, risk
      factors, and association with outcome.
AB  - PURPOSE: Data on the incidence of, risk factors for, and association with
      outcomes of acute kidney injury (AKI) after pediatric liver transplantation are
      scarce. We conducted a retrospective cohort study to determine the incidence of
      AKI after pediatric liver transplantation. In addition, we examined risk factors
      for AKI and association of AKI with outcomes. METHODS: This study included 156
      children aged between 3 months and 18 years undergoing liver transplantation at
      Kyoto University Hospital. AKI was defined according to the Kidney Disease:
      Improving Global Outcomes guidelines based on serum creatinine and urine output.
      We used multivariable logistic regression with stepwise variable selection to
      identify independent risk factors for AKI. RESULTS: AKI occurred in 72 patients
      (46.2%); 34 (21.8%) had stage 1, 32 (20.5%) had stage 2, and 6 (3.8%) had stage 3
      AKI. Factors independently associated with the development of AKI were increased
      preoperative total bilirubin level (adjusted odds ratio, 1.04 per 1 mg/dl; 95%
      confidence interval, 1.01-1.09; P = 0.026) and increased intraoperative blood
      loss (adjusted odds ratio, 1.03 per 10 ml/kg; 95% confidence interval, 1.00-1.06;
      P = 0.022). AKI was significantly associated with prolonged hospitalization
      (median, 61 vs. 46 days; P = 0.028). In-hospital mortality rate was 4.2% in
      patients with AKI and 3.6% in those without AKI (P = 1.000). CONCLUSION: The
      incidence of AKI after pediatric liver transplantation was 46.2%. Increased
      preoperative total bilirubin level and increased intraoperative blood loss were
      independently associated with the development of AKI. AKI was associated with
      prolonged hospitalization.

PMID- 28766022
TI  - Nickel oxide/carbon nanotube/polyaniline nanocomposite as bifunctional anode
      catalyst for high-performance Shewanella-based dual-chamber microbial fuel cell.
AB  - A novel nickel oxide/carbon nanotube/polyaniline (NCP) nanocomposite has been
      prepared and used to modify the electrocatalytic properties of carbon cloth anode
      in fabricating dual-chamber MFC. The prepared nanocomposite was characterized by
      scanning electron microscopy, X-ray diffraction, and fourier transform infrared
      spectroscopy. The carbon cloth coated with the NCP nanocomposite showed the
      enhanced electrochemical performance as compared to bare carbon cloth anode. The
      electrochemical properties of the fabricated MFC with the modified anode have
      been investigated by linear sweep voltammetry and electrochemical impedance
      spectroscopy. The maximum power density of the MFC using the novel NCP
      nanocomposite-carbon cloth anode increased by 61.88% compared to that of the bare
      carbon cloth anode. In comparison to the bare carbon cloth anode, the new
      composite anode showed 26.8% enhancement of current density output which it can
      be due to the enhancement of the charge transfer capability.

PMID- 28766023
TI  - How I do it-optimizing radiofrequency ablation in spinal metastases using iCT and
      navigation.
AB  - BACKGROUND: Exact positioning of the radiofrequency ablation (RFA) probe for
      tumor treatment under fluoroscopic guidance can be difficult because of
      potentially small inaccessible lesions and the radiation dose to the medical
      staff in RFA. In addition, vertebroplasty (VP) can be significantly high. METHOD:
      Description and workflow of RFA in spinal metastasis using iCT (intraoperative
      computed tomography) and 3D-navigation-based probe placement followed by VP.
      CONCLUSION: RFA and VP can be successfully combined with iCT-based navigation,
      which leads to a reduction of radiation to the staff and optimal probe
      positioning due to 3D navigation.

PMID- 28766024
TI  - Usefulness of intraoperative electromyographic monitoring of oculomotor and
      abducens nerves during skull base surgery.
AB  - BACKGROUND: Intraoperative neurophysiologic monitoring of the extraocular cranial
      nerve (EOCN) is not commonly performed because of technical difficulty and risk,
      reliability of the result and predictability of the postoperative function of the
      EOCN. METHODS: We performed oculomotor nerve (CN III) and abducens nerve (CN VI)
      intraoperative monitoring in patients with skull base surgery by recording the
      spontaneous muscle activity (SMA) and compound muscle action potential (CMAP).
      Two types of needle electrodes of different length were percutaneously inserted
      into the extraocular muscles with the free-hand technique. We studied the
      relationships between the SMA and CMAP and postoperative function of CN III and
      CN VI. RESULTS: A total of 23 patients were included. Nineteen oculomotor nerves
      and 22 abducens nerves were monitored during surgery, respectively. Neurotonic
      discharge had a positive predictive value of less than 50% and negative
      predictive value of more than 80% for postoperative CN III and CN VI dysfunction.
      The latency of patients with postoperative CN III dysfunction was 2.79 +/- 0.13
      ms, longer than that with intact CN III function (1.73 +/- 0.11 ms). One patient
      had transient CN VI dysfunction, whose CMAP latency (2.54 ms) was longer than
      that of intact CN VI function (2.11 +/- 0.38 ms). There was no statistically
      significant difference between patients with paresis and with intact function.
      CONCLUSIONS: The method of intraoperative monitoring of EOCNs described here is
      safe and useful to record responses of SMA and CMAP. Neurotonic discharge seems
      to have limited value in predicting the postoperative function of CN III and CN
      VI. The onset latency of CMAP longer than 2.5 ms after tumor removal is probably
      relevant to postoperative CN III and CN VI dysfunction. However, a definite
      quantitative relationship has not been found between the amplitude and
      stimulation intensity of CMAP and the postoperative outcome of CN III and CN VI.

PMID- 28766025
TI  - Determinants of botulinum toxin discontinuation in multiple sclerosis: a
      retrospective study.
AB  - The purpose of the present study was to investigate the long-term persistence to
      treatment with botulinum toxin type A (BoNT-A) for multiple sclerosis (MS)
      related spasticity and the determinants of BoNT-A discontinuation in daily
      clinical setting. We retrospectively collected data of patients who started BoNT
      A injections and underwent regular follow-up visits. Determinants of BoNT-A
      discontinuation were explored in a time-to-event Cox regression analysis which
      included as independent variables a large set of demographic and clinical
      characteristics. A total of 185 patients started BoNT-A injections from 2002 to
      2014 and were followed up to September 2016. Of them, data on 121 were considered
      in our analysis. At follow-up, 53 (44%) patients were still on treatment and 68
      (56%) patients discontinued BoNT-A after a median time of 1.2 years [interval 6
      months to 7.4 years]. The reasons for discontinuation were loss of efficacy (n =
      45), logistic problems or barriers to reach the structure (n = 16), and adverse
      events (n = 7). The absence of caregiver (hazard ratio = 1.69, p = 0.03) and lack
      of regular rehabilitation (hazard ratio = 1.78, p = 0.02) were two independent
      predictors for BoNT-A discontinuation. Our study confirms the beneficial effect
      of combining BoNT-A injections with rehabilitation and highlights the crucial
      role of caregivers for achieving better long-term outcomes in people with MS
      suffering from spasticity.

PMID- 28766026
TI  - Rectal Douching Among Men Who Have Sex with Men in Paris: Implications for
      HIV/STI Risk Behaviors and Rectal Microbicide Development.
AB  - Rectal douching is a common but potentially risky practice among MSM; MSM who
      douche may be ideal candidates for rectal microbicides as HIV prevention. Herein
      we explored rectal douching and its association with condomless receptive anal
      intercourse (CRAI), group sex, rates of HIV and other STIs, and likelihood to use
      rectal microbicide gels. We recruited a sample of 580 MSM from a geosocial
      networking smartphone application in Paris, France in 2016. Regression models
      estimated adjusted risk ratios (aRRs) for associations between rectal douche use
      and (1) engagement in CRAI, (2) group sex, (3) self-reported HIV and STI
      diagnoses, and (4) likelihood to use rectal microbicide gels for HIV prevention.
      54.3% of respondents used a rectal douche or enema in the preceding 3 months.
      Douching was significantly associated with CRAI (aRR: 1.77), participation in
      group sex (aRR: 1.42), HIV infection (aRR: 3.40), STI diagnosis (aRR: 1.73), and
      likelihood to use rectal microbicide gels (aRR: 1.78). Rectal douching is common
      among MSM, particularly those who practice CRAI, and rectal microbicide gels may
      be an acceptable mode of HIV prevention for MSM who use rectal douches.

PMID- 28766027
TI  - Telephone-Delivered Mindfulness Training for People Living with HIV: A
      Qualitative 360 degrees  Inquiry.
AB  - For people living with HIV and AIDS (PLWHA), life stress often undermines quality
      of life and interferes with medical care. Mindfulness training (MT) may help
      PLWHA to manage stress. Because standard MT protocols can be burdensome, we
      explored telephone delivery as a potentially more feasible approach. We used an
      innovative 360 degrees  qualitative inquiry to seek input regarding telephone
      delivery of MT for PLWHA in advance of a planned intervention trial. We also
      sought input on a time- and attention-matched control. Twenty five HIV patients,
      providers and advocates, were recruited to five focus groups. Participants
      understood the construct of mindfulness and recognized its potential benefits for
      stress management and improving medication adherence. Patients preferred the term
      "mindfulness" to meditation. Telephone-delivery appealed to all patients but
      several challenges were raised. Topics for the control intervention included
      nutrition, sleep, and aging. The 360 degrees  approach allowed three groups
      (patients, providers, advocates) to influence intervention development.

PMID- 28766028
TI  - A Hybrid 2D/3D User Interface for Radiological Diagnosis.
AB  - This paper presents a novel 2D/3D desktop virtual reality hybrid user interface
      for radiology that focuses on improving 3D manipulation required in some
      diagnostic tasks. An evaluation of our system revealed that our hybrid interface
      is more efficient for novice users and more accurate for both novice and
      experienced users when compared to traditional 2D only interfaces. This is a
      significant finding because it indicates, as the techniques mature, that hybrid
      interfaces can provide significant benefit to image evaluation. Our hybrid system
      combines a zSpace stereoscopic display with 2D displays, and mouse and keyboard
      input. It allows the use of 2D and 3D components interchangeably, or
      simultaneously. The system was evaluated against a 2D only interface with a user
      study that involved performing a scoliosis diagnosis task. There were two user
      groups: medical students and radiology residents. We found improvements in
      completion time for medical students, and in accuracy for both groups. In
      particular, the accuracy of medical students improved to match that of the
      residents.

PMID- 28766030
TI  - Erratum to: Pre-alcoholic fermentation acidification of red grape must using
      Lactobacillus plantarum.

PMID- 28766031
TI  - Is There a Future for Therapists?

PMID- 28766029
TI  - Ratio of blood urea nitrogen to serum creatinine at initiation of dialysis is
      associated with mortality: a multicenter prospective cohort study.
AB  - BACKGROUND: Some studies have shown that the estimated glomerular filtration rate
      (eGFR) at the time of initiating dialysis was associated with mortality. However,
      the relationship between ratio of blood urea nitrogen to serum creatinine
      (BUN/Cr) and mortality is unknown. METHODS: The study was a multicenter,
      prospective cohort analysis including 1520 patients. Patients were classified
      into four quartiles based on the BUN/Cr ratio at the dialysis initiation, with Q1
      having the lowest ratio and Q4 the highest. All-cause mortality after initiating
      dialysis was compared using the log-rank test. All-cause mortality of Q1, Q2, and
      Q3 was compared with that of Q4 using multivariate Cox proportional hazard
      regression analysis. Moreover, we compared the renal parameters including BUN/Cr
      ratio, eGFR, and creatinine clearance for sensitivity and specificity using
      receiver operative characteristic (ROC) curve. RESULTS: Significant differences
      were observed in all-cause mortality among the four groups (p < 0.001).
      Multivariate analysis revealed that all-cause mortality was significantly higher
      in Q4 than in Q1 [hazard ratio (HR) = 1.82, 95% confidence interval (CI) 1.24
      2.67, p = 0.002]. The increase in BUN/Cr ratio was positively associated with
      mortality (HR 1.04, 95% CI 1.02-1.06, p = 0.002). The sensitivity and specificity
      of BUN/Cr ratio for 180, 365, 730, and 1095 days mortality ranged between 0.60
      0.72 and 0.59-0.71, respectively. The area under the curve of BUN/Cr for all
      cause mortality was the highest among the renal parameters. CONCLUSION: The
      BUN/Cr ratio at the time of initiation of dialysis was associated with all-cause
      mortality.

PMID- 28766032
TI  - Fluorinated Methacrylamide Chitosan Hydrogels Enhance Cellular Wound Healing
      Processes.
AB  - Low availability of oxygen can lead to stalled wound healing processes and
      chronic wounds. To address local hypoxia and to better understand direct cellular
      benefits, a perfluorocarbon conjugated chitosan (MACF) hydrogel that delivers
      oxygen was created and applied for the first time to in vitro cultures of human
      dermal fibroblasts and human epidermal keratinocytes under both normoxic (21% O2)
      and hypoxic (1% O2) environments. Results revealed that local application of MACF
      provided 233.8 +/- 9.9 mmHg oxygen partial pressure at 2 h and maintained
      equilibrium oxygen levels that were approximately 17 mmHg partial pressure
      greater than untreated controls. Cell culture experiments showed that MACF
      oxygenating gels improved cellular functions involved in wound healing such as
      cell metabolism, total DNA synthesis and cell migration under hypoxia in both
      fibroblasts and keratinocytes. Adenosine triphosphate (ATP) quantification also
      revealed that MACF treatments improved cellular ATP levels significantly over
      controls under both normoxia and hypoxia (p < 0.005). In total, these studies
      provide new data to indicate that supplying local oxygen via MACF hydrogels under
      hypoxic environments improves key wound healing cellular functions.

PMID- 28766033
TI  - Antifungal mechanism of the combination of Cinnamomum verum and Pelargonium
      graveolens essential oils with fluconazole against pathogenic Candida strains.
AB  - The present study aimed to investigate the anti-Candida activity of ten essential
      oils (EOs) and to evaluate their potential synergism with conventional drugs. The
      effect on secreted aspartic protease (SAP) activity and the mechanism of action
      were also explored. The antifungal properties of essential oils were investigated
      using standard micro-broth dilution assay. Only Cinnamomum verum, Thymus
      capitatus, Syzygium aromaticum, and Pelargonium graveolens exhibited a broad
      spectrum of activity against a variety of pathogenic Candida strains. Chemical
      composition of active essential oils was performed by gas chromatography-mass
      spectrometry (GC-MS). Synergistic effect was observed with the combinations C.
      verum/fluconazole and P. graveolens/fluconazole, with FIC value 0.37.
      Investigation of the mechanism of action revealed that C. verum EO reduced the
      quantity of ergosterol to 83%. A total inhibition was observed for the
      combination C. verum/fluconazole. However, P. graveolens EO may disturb the
      permeability barrier of the fungal cell wall. An increase of MIC values of P.
      graveolens EO and the combination with fluconazole was observed with
      osmoprotectants (sorbitol and PEG6000). Furthermore, the combination with
      fluconazole may affect ergosterol biosynthesis and disturb fatty acid homeostasis
      in C. albicans cells as the quantity of ergosterol and oleic acid was reduced to
      52.33 and 72%, respectively. The combination of P. graveolens and C. verum EOs
      with fluconazole inhibited 78.31 and 64.72% SAP activity, respectively. To our
      knowledge, this is the first report underlying the mechanism of action and the
      inhibitory effect of SAP activity of essential oils in synergy with fluconazole.
      Naturally occurring phytochemicals C. verum and P. graveolens could be effective
      candidate to enhance the efficacy of fluconazole-based therapy of C. albicans
      infections.

PMID- 28766034
TI  - The Hog1-like MAPK Mpk3 collaborates with Hog1 in response to heat shock and
      functions in sustaining the biological control potential of a fungal insect
      pathogen.
AB  - The mitogen-activated protein kinase (MAPK) Mpk3/MpkC resembles the MAPK Hog1 but
      does not necessarily function in some filamentous fungi. Here, we compared
      functions of Mpk3 and Hog1 in Beauveria bassiana, a filamentous fungal insect
      pathogen, by multi-phenotypic analyses of their single/double deletion mutants.
      Growth defects of Deltampk3 were moderate on all 14 minimal media with different
      carbon or nitrogen sources and less severe than those of Deltahog1 on most media
      tested. The double deletion mutant suffered significantly more severe growth
      defects than those observed in Deltampk3 and Deltahog1, suggesting overlapping
      and collaborative roles of Mpk3 and Hog1 in uptake of six carbon and four
      nitrogen sources during normal growth. Despite little impact on conidiation
      capacity, mpk3 deletion slowed down conidial germination as much as hog1 or
      double deletion. Conidial resistance to UV-B irradiation decreased less in
      Deltampk3 than in Deltahog1 or in the double mutant. The fungal virulence was
      similarly attenuated for all deletion mutants against Galleria mellonella larvae
      through normal cuticle infection. Intriguingly, the Deltampk3 mutant displayed
      null response to high osmolarity and fludioxonil fungicide, to which both
      Deltahog1 and double mutants were hypersensitive and highly resistant,
      respectively, but it was more sensitive to a 3-h heat shock at 40  degrees C than
      Deltahog1 during normal incubation. Western blot hybridization demonstrated that
      Mpk3 could collaborate with Hog1 in response to heat shock rather than to the
      chemical stresses. Altogether, Mpk3 collaborates with Hog1 only in response to
      heat shock and functions in sustaining the pest control potential of B. bassiana.

PMID- 28766035
TI  - Valuable biochemical production in mixed culture fermentation: fundamentals and
      process coupling.
AB  - The mixed culture fermentation is an important environmental biotechnology that
      converts biodegradable organic wastes to valuable chemicals such as hydrogen,
      methane, acetate, ethanol, propionate, and so on. For the multistep process of
      hydrolysis, acidogenesis, acetogenesis/homoacetogensis, and methanogenesis, the
      typical metabolic reactions are firstly summarized. And then, since the final
      metabolites are always a mixture, the separation and purification processes are
      necessary to couple with anaerobic fermentation. Therefore, several typical
      coupling technologies including biogas upgrading, two-stage fermentation, gas
      stripping, membrane technology of pervaporation, membrane distillation,
      electrodialysis, bipolar membrane electrodialysis, and microbial fuel cells are
      summarized to separate the metabolites and recover energy. At last, the novel
      technologies such as the controlled metabolite production, medium chain
      carboxylic acid production, and high temperature ethanol recovery in thermophilic
      mixed culture fermentation are also reviewed. However, the novel concepts are
      still needed to meet the demands of better overall performances and lower total
      costs.

PMID- 28766036
TI  - Evaluation of the antimicrobial activities of ultrasonicated spinach leaf
      extracts using RAPD markers and electron microscopy.
AB  - Spinach (Spinacia oleracea L.) leaves represent an important dietary source of
      nutrients, antioxidants and antimicrobials. As such, spinach leaves play an
      important role in health and have been used in the treatment of human diseases
      since ancient times. Here, the aims were to optimize the extraction methods for
      recovering antimicrobial substances of spinach leaves, determine the minimum
      inhibitory concentrations (MICs) of the antimicrobial substances against
      Escherichia coli and Staphylococcus aureus and, finally, evaluate the effects of
      spinach leaves' antimicrobials on bacterial DNA using central composite face
      centered methods. The effect of the extracts on both Gram-positive and Gram
      negative bacterial models was examined by scanning electron microscopy (SEM) and
      random amplification of polymorphic (bacterial) DNA (RAPD). The optimal
      extraction conditions were at 45  degrees C, ultrasound power of 44% and an
      extraction time of 23 min. The spinach extracts exhibited antimicrobial
      activities against both bacteria with MICs in the 60-100 mg/ml range.
      Interestingly, SEM showed that the treated bacterial cells appear damaged with a
      reduction in cell number. RAPD analysis of genomic DNA showed that the number and
      sizes of amplicons were decreased by treatments. Based on these results, it was
      inferred that spinach leaf extracts exert bactericidal activities by both
      inducing mutations in DNA and causing cell wall disruptions.

PMID- 28766037
TI  - Did Rev-1 small ruminants vaccination helped improve cattle brucellosis
      prevalence status in Algeria?
AB  - In 2006, the Algerian authorities started the Rev-1 vaccination of sheep and
      goats; consequently, there was a significant improvement of small ruminant
      brucellosis sanitary status. In this paper, we attempt to study the effect of Rev
      1 small ruminants' vaccination on cattle brucellosis prevalence in Algeria. Our
      results showed an overall cattle herd seroprevalence of 12% (9 positive herds of
      75). The risk factor analysis using a logistic regression model indicated that
      the presence of small ruminants along with cattle in the herd (mixed herds)
      decreased the odds for brucellosis seropositivity by 1.69 [95% CI 0.54-2.84; P =
      0.042] compared to the cattle herds only. Likewise, the present study showed that
      the presence of Rev-1 vaccinated small ruminants in the herd decreased also the
      odds for brucellosis seropositivity by 4.10 [95% CI 3.20-5.00; P = 0.003]
      compared to other herds. This result lead to the assumption that the small
      ruminants Rev-1 vaccination diminish Brucella microbisme pressure in the mixed
      herds and help decrease the cattle brucellosis prevalence in these herds.

PMID- 28766038
TI  - Intensive grazing and maize silage to enhance the sustainability of small-scale
      dairy systems in the highlands of Mexico.
AB  - The effects of two innovative feeding strategies-intensive grazing (GR) and maize
      silage (MS)-on the sustainability of small-scale dairy systems (SSDS) were
      assessed in the highlands of central Mexico. On a total of 24 farms, four
      innovations were adopted between 2011 and 2014. Five farms continued their
      conventional feeding strategy (CC) of cut-and-carry pasture supplemented with
      commercial concentrate and ground corn grain, as well as straws (maize, oat, and
      wheat) in the dry season of feed scarcity; six farms implemented MS in the dry
      season; six farms GR of pastures; and seven farms implemented both GR and MS.
      Assessment in 2015 showed that farms which implemented both GR and MS had a
      higher local diversity score (P <= 0.001), higher scores for ethics and human
      development, and a higher score in economic independence (P <= 0.05) than farms
      that implemented only one of the innovations. The overall sustainability score
      (with range 0-100) was 46 for CC, 47 for MS, 52 for GR, and 55 for GR + MS. The
      innovations reduced feeding costs and enhanced sustainability, particularly when
      GR + MS were both implemented.

PMID- 28766039
TI  - Fungal and Bacterial Diversity of Airway Microbiota in Adults with Cystic
      Fibrosis: Concordance Between Conventional Methods and Ultra-Deep Sequencing, and
      Their Practical use in the Clinical Laboratory.
AB  - Given the complexity of the airway microbiota in the respiratory tract of cystic
      fibrosis (CF) patients, it seems crucial to compile the most exhaustive and exact
      list of the microbial communities inhabiting CF airways. The aim of the present
      study was to compare the bacterial and fungal diversity of sputa from adult CF
      patients during non-exacerbation period by culture-based and molecular methods,
      and ultra-deep-sequencing (UDS). Sputum samples from four CF patients were
      cultured and analysed by DNA extractions followed by terminal restriction
      fragment length polymorphism analysis through resolution of bacterial ribosomal
      gene (rDNA) fragments, and cloning plus sequencing of part of fungal rRNA genes.
      These approaches were compared with UDS method targeting 16S rDNA gene and the
      internal transcribed spacer (ITS) 2 region of rDNA. A total of 27 bacterial and
      18 fungal genera were detected from the four patients. Five (18%) and 3 (16%)
      genera were detected by culture for bacteria and fungi, respectively, 9 (33%) and
      3 (16%) by first generation sequencing (FGS) methods, and 26 (96%) and 18 (100%)
      by UDS. The mean number of genera detected by UDS per patient was statistically
      higher than by culture or FGS methods. Patients with severe airway disease as
      assessed by standard spirometry exhibited a reduced fungal and bacterial
      diversity. UDS approach evaluates more extensively the diversity of fungal and
      bacterial flora compared with cultures. However, it currently remains difficult
      to routinely use UDS mainly because of the lack of standardization, and the
      current cost of this method.

PMID- 28766042
TI  - Estimating population heat exposure and impacts on working people in conjunction
      with climate change.
AB  - Increased environmental heat levels as a result of climate change present a major
      challenge to the health, wellbeing and sustainability of human communities in
      already hot parts of this planet. This challenge has many facets from direct
      clinical health effects of daily heat exposure to indirect effects related to
      poor air quality, poor access to safe drinking water, poor access to nutritious
      and safe food and inadequate protection from disease vectors and environmental
      toxic chemicals. The increasing environmental heat is a threat to environmental
      sustainability. In addition, social conditions can be undermined by the negative
      effects of increased heat on daily work and life activities and on local cultural
      practices. The methodology we describe can be used to produce quantitative
      estimates of the impacts of climate change on work activities in countries and
      local communities. We show in maps the increasing heat exposures in the shade
      expressed as the occupational heat stress index Wet Bulb Globe Temperature. Some
      tropical and sub-tropical areas already experience serious heat stress, and the
      continuing heating will substantially reduce work capacity and labour
      productivity in widening parts of the world. Southern parts of Europe and the USA
      will also be affected. Even the lowest target for climate change (average global
      temperature change = 1.5  degrees C at representative concentration pathway
      (RCP2.6) will increase the loss of daylight work hour output due to heat in many
      tropical areas from less than 2% now up to more than 6% at the end of the
      century. A global temperature change of 2.7  degrees C (at RCP6.0) will double
      this annual heat impact on work in such areas. Calculations of this type of heat
      impact at country level show that in the USA, the loss of work capacity in
      moderate level work in the shade will increase from 0.17% now to more than 1.3%
      at the end of the century based on the 2.7  degrees C temperature change. The
      impact is naturally mainly occurring in the southern hotter areas. In China, the
      heat impact will increase from 0.3 to 2%, and in India, from 2 to 8%. Especially
      affected countries, such as Cambodia, may have losses going beyond 10%, while
      countries with most of the population at high cooler altitude, such as Ethiopia,
      may experience much lower losses.

PMID- 28766043
TI  - Intestinal macrophages in Peyer's patches, sacculus rotundus and appendix of
      Angora rabbit.
AB  - The largest pool of macrophages in the body is harboured by the intestinal
      mucosa. As the principal phagocytic component of the immune system, macrophages
      are essential for maintaining mucosal homeostasis as they prevent commensal
      bacteria from adhering to mucosal epithelial cells. This study provides a RAM11
      immunohistochemical and electron microscopic investigation of the existence,
      localization and distribution of intestinal macrophages in organized gut
      associated lymphoid tissue (GALT), including Peyer's patches (PPs), the sacculus
      rotundus (SR) and the appendix, in the Angora rabbit. Although rabbit intestinal
      macrophages did not express the tissue macrophage marker macrosialin (CD68), they
      expressed RAM11. RAM11-positive intestinal macrophages were mostly localized to
      the subepithelial dome region, interfollicular area and germinal centres (GCs) of
      the GALT and the lamina propria or submucosa of the ileum and jejunum devoid of
      PPs and were also observed in the follicle-associated epithelium of PPs, but not
      in that of the SR and appendix. RAM11-positive macrophages containing engulfed
      apoptotic bodies were present in the GCs of the lymphoid follicles in the GALT.
      Electron microscopy further revealed multiple macrophages containing apoptotic
      bodies within the GCs of the follicles in the GALT. Some macrophage aggregations
      were observed in the GC and between the GC and the corona region of the follicles
      in the SR and appendix. Rabbit intestinal macrophages thus undertake both potent
      phagocytic activity and the efficient scavenging of apoptotic cells.
      Immunohistochemical data suggest that RAM11 can be reliably used for the
      determination of intestinal macrophages in the GALT of rabbits.

PMID- 28766041
TI  - The role of the basal ganglia in the control of seizure.
AB  - Epilepsy is a network disorder and each type of seizure involves distinct
      cortical and subcortical network, differently implicated in the control and
      propagation of the ictal activity. The role of the basal ganglia has been
      revealed in several cases of focal and generalized seizures. Here, we review the
      data that show the implication of the basal ganglia in absence, temporal lobe,
      and neocortical seizures in animal models (rodent, cat, and non-human primate)
      and in human. Based on these results and the advancement of deep brain
      stimulation for Parkinson's disease, basal ganglia neuromodulation has been
      tested with some success that can be equally seen as promising or disappointing.
      The effect of deep brain stimulation can be considered promising with a 76% in
      seizure reduction in temporal lobe epilepsy patients, but also disappointing,
      since only few patients have become seizure free and the antiepileptic effects
      have been highly variable among patients. This variability could probably be
      explained by the heterogeneity among the patients included in these clinical
      studies. To illustrate the importance of specific network identification,
      electrophysiological activity of the putamen and caudate nucleus has been
      recorded during penicillin-induced pre-frontal and motor seizures in one monkey.
      While an increase of the firing rate was found in putamen and caudate nucleus
      during pre-frontal seizures, only the activity of the putamen cells was increased
      during motor seizures. These preliminary results demonstrate the implication of
      the basal ganglia in two types of neocortical seizures and the necessity of
      studying the network to identify the important nodes implicated in the
      propagation and control of each type of seizure.

PMID- 28766044
TI  - Analysis of gene expression and functional characterization of XPR1: a pathogenic
      gene for primary familial brain calcification.
AB  - Primary familial brain calcification (PFBC) is a neuropsychiatric disorder
      characterized by bilateral cerebral calcification with diverse neurologic or
      psychiatric symptoms. Recently, XPR1 variation has accounted for PFBC as another
      new causative gene. However, little is known about the distribution and basic
      function of XPR1 and its interaction with the other three pathogenic genes for
      PFBC (SLC20A2, PDGFRB and PDGFB). The aim of this study was to further clarify
      the role of XPR1 in PFBC brain pathology. As a result, gene expression profiles
      showed that XPR1 mRNA was widely expressed throughout the mouse brain. Cerebellum
      and striatum, most commonly affected in PFBC, contained a higher level of XPR1
      protein than other brain regions. Additionally, XPR1 deficiency seriously
      affected Pi efflux and XPR1 mutations seemed to have an effect through
      haploinsufficiency mechanism. The immunoprecipitation and immunohistochemical
      studies demonstrated that XPR1 could interact with PDGFRB and might form a
      complex on the cell membrane. These results suggested that XPR1 played a
      fundamental role in the maintenance of cellular phosphate balance in the brain.
      This provided us with a novel perspective on understanding the pathophysiology of
      PFBC. The expression networks and interaction with the known pathogenic genes
      could shed new light on additional candidate genes for PFBC.

PMID- 28766040
TI  - The diabetic brain and cognition.
AB  - The prevalence of both Alzheimer's disease (AD) and vascular dementia (VaD) is
      increasing with the aging of the population. Studies from the last several years
      have shown that people with diabetes have an increased risk for dementia and
      cognitive impairment. Therefore, the authors of this consensus review tried to
      elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD
      and VaD. Based on the clinical and experimental work of scientists from 18
      countries participating in the International Congress on Vascular Disorders and
      on literature search using PUBMED, it can be concluded that T2DM is a risk factor
      for both, AD and VaD, based on a pathology of glucose utilization. This pathology
      is the consequence of a disturbance of insulin-related mechanisms leading to
      brain insulin resistance. Although the underlying pathological mechanisms for AD
      and VaD are different in many aspects, the contribution of T2DM and insulin
      resistant brain state (IRBS) to cerebrovascular disturbances in both disorders
      cannot be neglected. Therefore, early diagnosis of metabolic parameters including
      those relevant for T2DM is required. Moreover, it is possible that therapeutic
      options utilized today for diabetes treatment may also have an effect on the risk
      for dementia. T2DM/IRBS contribute to pathological processes in AD and VaD.

PMID- 28766045
TI  - PAD2 overexpression in transgenic mice augments malignancy and tumor-associated
      inflammation in chemically initiated skin tumors.
AB  - We previously found that transgenic mice overexpressing MMTV-FLAG-hPAD2 (PAD2OE)
      developed spontaneous skin lesions, with a subset of these lesions progressing to
      invasive squamous cell carcinoma (SCC). The goal of this report was to better
      understand the potential mechanisms by which PAD2 overexpression promotes skin
      cancer. Here, PAD2OE mice were treated with the carcinogen, 9,10-dimethyl-1,2
      benzanthracene and with O-tetradecanoylphorbol-13-acetate and then scored for
      papilloma formation. Additionally, tumor sections were evaluated for evidence of
      tumor cell invasion and inflammation. We found that the total number of
      papillomas was significantly increased in PAD2OE mice compared to controls.
      Histopathologic analysis of the lesions found that in PAD2OE skin tumors
      progressed to invasive SCC more frequently than controls. Additionally, we found
      that PAD2OE lesions were highly inflamed, with a dense inflammatory cell
      infiltrate and an associated increase in nuclear phospho-STAT3 (signal transducer
      and activator of transcription 3) in the transgenic tumors. These data suggest
      that overexpression of the hPAD2 transgene in the epidermis increases the
      malignant conversion rate of benign tumors by promoting an inflammatory
      microenvironment.

PMID- 28766046
TI  - Relationship between left ventricular diastolic dysfunction and very late
      recurrences after multiple procedures for atrial fibrillation ablation.
AB  - Although very late recurrences (VLRs) (first recurrence >12 months after the last
      catheter ablation) of atrial fibrillation (AF) after multiple catheter ablation
      procedures are rare, it remains a critical issue. The risk factors for VLRs
      remain largely unclear. From December 2011 to April 2014, 253 patients underwent
      an initial catheter ablation. Of the 253 patients, 21 had AF recurrences within 1
      year after the last catheter ablation. The study was conducted in the remaining
      232 patients. Left ventricular diastolic dysfunction (LVDD) was assessed by
      echocardiography using composite categories with tissue Doppler imaging and left
      atrial volume measurements, i.e., a septal e' < 8 cm/s, lateral e' < 10 cm/s, and
      left atrium volume index (LAV/body surface area) (LAVI) >=34 mL/m2. LVDD was
      observed in 40 patients. Sinus rhythm was preserved in 220 patients after
      multiple catheter procedures, and 12 had VLRs. The clinical factors possibly
      related to VLRs were examined, and a multivariate regression analysis showed that
      LVDD was the only independent risk factor for VLRs (hazard ratio: 10.31, 95%
      confidence interval: 2.78-38.18, P < 0.0001). LVDD at baseline is a risk factor
      for a VLR after multiple catheter ablation procedures for AF.

PMID- 28766047
TI  - Prognostic value of cardiovascular magnetic resonance imaging for life
      threatening arrhythmia detected by implantable cardioverter-defibrillator in
      Japanese patients with hypertrophic cardiomyopathy.
AB  - Implantable cardioverter-defibrillator (ICD) is effective to prevent sudden death
      in HCM patients. We reviewed ICD records to analyze the relation between life
      threatening arrhythmia and late gadolinium enhancement (LGE) on cardiovascular
      magnetic resonance (CMR) in Japanese hypertrophic cardiomyopathy (HCM) patients.
      In 102 consecutive patients (median age 63 years, 63 males) implanted with an ICD
      after CMR with gadolinium enhancement (median follow-up 2.8 years), the outcome
      of life-threatening arrhythmic events (appropriate ICD interventions for
      ventricular tachycardia or ventricular fibrillation) was examined. Appropriate
      interventions rate were 10.3% per year for secondary prevention and 7.4% per year
      for primary prevention. The annualized ICD-related complication rate was 3.7%.
      43/91 patients (47%) implanted ICD for primary prevention had maximum wall
      thickness >=20 mm plus LGE in >=4 of 17 left ventricular segments (cut-off value
      obtained from ROC curve); the appropriate ICD intervention rate was significantly
      higher in this group than in other patients group (annualized event rate, 11.1
      vs. 4.6%; log-rank P = 0.038). A combination of myocardial hypertrophy and LGE is
      a useful outcome predictive factor for life-threatening ventricular arrhythmia in
      Japanese HCM patients.

PMID- 28766048
TI  - Association of epicardial adipose tissue with coronary spasm and coronary
      atherosclerosis in patients with chest pain: analysis of data collated by the
      KoRean wOmen'S chest pain rEgistry (koROSE).
AB  - Epicardial adipose tissue (EAT) represents a cardio-metabolic risk factor; it
      secretes several adipokines related to coronary atherosclerosis. However, the
      precise relationship between EAT and coronary vasospasm is unknown. This study
      aimed to investigate the relationship between EAT and coronary vasospasm using
      data from the KoRean wOmen'S chest pain rEgistry (koROSE). This study included
      551 patients (female/male = 366/185; mean age = 60.2 +/- 10.2 years) who
      presented with chest pain at an outpatient clinic, and who subsequently underwent
      echocardiography and coronary angiography. Coronary artery stenosis (CAS >50%
      narrowing of at least one coronary artery) was detected in 223 patients (40.5%).
      The remaining 328 patients underwent the coronary spasm provocation test.
      Coronary spasm was defined as >90% narrowing induced by intra-coronary
      acetylcholine or ergonovine injection. EAT thickness was measured using
      transthoracic echocardiography according to American society of echocardiography
      recommendations. The mean EAT thickness was higher in the patients with CAS than
      in those without (8.09 +/- 2.51 versus 6.88 +/- 2.54 mm, P = 0.001) after
      adjusting for factors potentially influencing EAT thickness. Coronary vasospasm
      by provocation test was detected in 128 patients. The EAT thickness was higher in
      the patients with spasm than in those without (7.65 +/- 2.52 versus 6.40 +/- 2.45
      mm, P < 0.001) but was not statistically different from that of the patients with
      CAS (P = 0.43). The EAT thickness had an independent relationship with CAS [odds
      ratio (OR) 1.166, 95% confidence interval (CI) 1.07-1.27, P < 0.001] and coronary
      vasospasm [OR 1.276, 95% CI 1.14-1.43, P < 0.001] after adjusting for clinical
      cardiovascular risk factors. EAT thickness is associated with coronary vasospasm
      and coronary atherosclerosis. The pathophysiology of coronary spasm may be
      similar to that of coronary atherosclerosis and could be an indicator of coronary
      stenosis.

PMID- 28766050
TI  - Unique XCI evolution in Tokudaia: initial XCI of the neo-X chromosome in Tokudaia
      muenninki and function loss of XIST in Tokudaia osimensis.
AB  - X chromosome inactivation (XCI) is an essential mechanism to compensate gene
      dosage in mammals. Here, we show that XCI has evolved differently in two species
      of the genus Tokudaia. The Amami spiny rat, Tokudaia osimensis, has a single X
      chromosome in males and females (XO/XO). By contrast, the Okinawa spiny rat,
      Tokudaia muenninki, has XX/XY sex chromosomes like most mammals, although the X
      chromosome has acquired a neo-X region by fusion with an autosome. BAC clones
      containing the XIST gene, which produces the long non-coding RNA XIST required
      for XCI, were obtained by screening of T. osimensis and T. muenninki BAC
      libraries. Each clone was mapped to the homologous region of the X inactivation
      center in the X chromosome of the two species by BAC-FISH. XIST RNAs were
      expressed in T. muenninki females, whereas no expression was observed in T.
      osimensis. The sequence of the XIST RNA was compared with that of mouse, showing
      that the XIST gene is highly conserved in T. muenninki. XIST RNAs were localized
      to the ancestral X region (Xq), to the heterochromatic region (pericentromeric
      region), and partially to the neo-X region (Xp). The hybridization pattern
      correlated with LINE-1 accumulation in Xq but not in Xp. Dosage of genes located
      on the neo-X chromosome was not compensated, suggesting that the neo-X region is
      in an early state of XCI. By contrast, many mutations were observed in the XIST
      gene of T. osimensis, indicating its loss of function in the XO/XO species.

PMID- 28766051
TI  - Real-time muscle state estimation from EMG signals during isometric contractions
      using Kalman filters.
AB  - State-space control of myoelectric devices and real-time visualization of muscle
      forces in virtual rehabilitation require measuring or estimating muscle dynamic
      states: neuromuscular activation, tendon force and muscle length. This paper
      investigates whether regular (KF) and extended Kalman filters (eKF), derived
      directly from Hill-type muscle mechanics equations, can be used as real-time
      muscle state estimators for isometric contractions using raw electromyography
      signals (EMG) as the only available measurement. The estimators' amplitude error,
      computational cost, filtering lags and smoothness are compared with usual EMG
      driven analysis, performed offline, by integrating the nonlinear Hill-type muscle
      model differential equations (offline simulations-OS). EMG activity of the three
      triceps surae components (soleus, gastrocnemius medialis and gastrocnemius
      lateralis), in three torque levels, was collected for ten subjects. The
      actualization interval (AI) between two updates of the KF and eKF was also
      varied. The results show that computational costs are significantly reduced (70x
      for KF and 17[Formula: see text] for eKF). The filtering lags presented sharp
      linear relationships with the AI (0-300 ms), depending on the state and
      activation level. Under maximum excitation, amplitude errors varied in the range
      10-24% for activation, 5-8% for tendon force and 1.4-1.8% for muscle length,
      reducing linearly with the excitation level. Smoothness, measured by the ratio
      between the average standard variations of KF/eKF and OS estimations, was greatly
      reduced for activation but converged exponentially to 1 for the other states by
      increasing AI. Compared to regular KF, extended KF does not seem to improve
      estimation accuracy significantly. Depending on the particular application
      requirements, the most appropriate KF actualization interval can be selected.

PMID- 28766049
TI  - UsnRNP biogenesis: mechanisms and regulation.
AB  - Macromolecular complexes composed of proteins or proteins and nucleic acids
      rather than individual macromolecules mediate many cellular activities.
      Maintenance of these activities is essential for cell viability and requires the
      coordinated production of the individual complex components as well as their
      faithful incorporation into functional entities. Failure of complex assembly may
      have fatal consequences and can cause severe diseases. While many macromolecular
      complexes can form spontaneously in vitro, they often require aid from assembly
      factors including assembly chaperones in the crowded cellular environment. The
      assembly of RNA protein complexes implicated in the maturation of pre-mRNAs
      (termed UsnRNPs) has proven to be a paradigm to understand the action of assembly
      factors and chaperones. UsnRNPs are assembled by factors united in protein
      arginine methyltransferase 5 (PRMT5)- and survival motor neuron (SMN)-complexes,
      which act sequentially in the UsnRNP production line. While the PRMT5-complex pre
      arranges specific sets of proteins into stable intermediates, the SMN complex
      displaces assembly factors from these intermediates and unites them with UsnRNA
      to form the assembled RNP. Despite advanced mechanistic understanding of UsnRNP
      assembly, our knowledge of regulatory features of this essential and ubiquitous
      cellular function remains remarkably incomplete. One may argue that the process
      operates as a default biosynthesis pathway and does not require sophisticated
      regulatory cues. Simple theoretical considerations and a number of experimental
      data, however, indicate that regulation of UsnRNP assembly most likely happens at
      multiple levels. This review will not only summarize how individual components of
      this assembly line act mechanistically but also why, how, and when the UsnRNP
      workflow might be regulated by means of posttranslational modification in
      response to cellular signaling cues.

PMID- 28766052
TI  - Prevalence of Parvovirus B19V in Hematological Malignancies and Chronic Anemia.

PMID- 28766053
TI  - Unusual Neuroimaging Finding in Infantile Tay-Sach's Disease.

PMID- 28766054
TI  - MRI Chest: A Game Changer?

PMID- 28766055
TI  - Non-synonymous WNT16 polymorphisms alleles are associated with different
      osteoarthritis phenotypes.
AB  - Hereditary factors have a strong influence on osteoarthritis (OA). The Wnt
      pathway is involved in bone and cartilage homeostasis. Hence, we hypothesized
      that allelic variations of WNT16 could influence the OA phenotype. We studied 509
      Caucasian patients undergoing joint replacement due to severe primary OA.
      Radiographs were used to classify the OA as atrophic or hypertrophic. Two
      nonsynonymous polymorphisms of WNT16 (rs2707466 and rs2908004) were analyzed. The
      association between the genotypes and the OA phenotype was analyzed by logistic
      regression and adjusted for age and body mass index. A genotype-phenotype
      association was found in the sex-stratified analysis. Thus, there was a
      significant difference in the genotypic frequencies of rs2707466 between
      hypertrophic and atrophic hip OA in males (p = 0.003), with overrepresentation of
      G alleles in the hypertrophic phenotype (OR 2.08; CI 1.28-3.38). An association
      in the same direction was observed between these alleles and the type of knee OA,
      with G alleles being more common in the hypertrophic than in atrophic knee
      phenotypes (p = 0.008; OR 1.956, CI 1.19-3.19). Similar associations were found
      for the rs2908004 SNP, but it only reached statistical significance for knee OA
      (p = 0.017; OR 0.92, CI 0.86-0.989). This is the first study attempting to
      explore the association of genetic variants with the OA phenotype. These data
      suggest the need to consider the OA phenotype in future genetic association
      studies of OA.

PMID- 28766056
TI  - [Anesthesia management in microsurgical reconstructions].
AB  - Microsurgical procedures for construction of anastomoses present new challenges
      for anesthetists in the perioperative setting. Despite their increasing
      importance, so far no perioperative management guidelines for these patients
      existed. Anesthetists can influence the success of surgery (e. g. successful
      perfusion of a flap) via an optimal preoperative, intraoperative and
      postoperative approach. Patients should be carefully evaluated preoperatively for
      increased risks to avoid poor postoperative outcomes. Perioperatively, the choice
      of anesthetic procedure as well as the management of fluid infusion, blood
      glucose, temperature and blood transfusion are of great importance. Adequate
      analgesia as well as strict control should be performed as soon as possible
      postoperatively, preferably in a surveillance unit to detect and treat any
      complications as early as possible.

PMID- 28766058
TI  - Bioselection of coxsackievirus B6 strain variants with altered tropism to human
      cancer cell lines.
AB  - Cancer cells develop increased sensitivity to members of many virus families and,
      in particular, can be efficiently infected and lysed by many low-pathogenic human
      enteroviruses. However, because of their great genetic heterogeneity, cancer
      cells display different levels of sensitivity to particular enterovirus strains,
      which may substantially limit the chances of a positive clinical response. We
      show that a non-pathogenic strain of coxsackievirus B6 (LEV15) can efficiently
      replicate to high titers in the malignant human cell lines C33A, DU145, AsPC-1
      and SK-Mel28, although it displays much lower replication efficiency in A431 and
      A549 cells and very limited replication ability in RD and MCF7 cells, as well as
      in the normal lung fibroblast cell line MRC-5 and the immortalized mammary
      epithelial cell line MCF10A. By serial passaging in RD, MCF7 and A431 cells, we
      obtained LEV15 strain variants that had acquired high replication capacity in the
      appropriate carcinoma cell lines without losing their high replication capability
      in the original set of cancer cell lines and had limited replication capability
      in untransformed cells. The strains demonstrated improved oncolytic properties in
      nude-mouse xenografts. We identified nucleotide changes responsible for the
      phenotypes and suggest a bioselection approach for a generation of oncolytic
      virus strains with a wider spectrum of affected tumors.

PMID- 28766057
TI  - Overview of the 2017 WHO Classification of Pituitary Tumors.
AB  - This review focuses on discussing the main changes on the upcoming fourth edition
      of the WHO Classification of Tumors of the Pituitary Gland emphasizing
      histopathological and molecular genetics aspects of pituitary neuroendocrine
      (i.e., pituitary adenomas) and some of the non-neuroendocrine tumors involving
      the pituitary gland. Instead of a formal review, we introduced the highlights of
      the new WHO classification by answering select questions relevant to practising
      pathologists. The revised classification of pituitary adenomas, in addition to
      hormone immunohistochemistry, recognizes the role of other immunohistochemical
      markers including but not limited to pituitary transcription factors. Recognizing
      this novel approach, the fourth edition of the WHO classification has abandoned
      the concept of "a hormone-producing pituitary adenoma" and adopted a pituitary
      adenohypophyseal cell lineage designation of the adenomas with subsequent
      categorization of histological variants according to hormone content and specific
      histological and immunohistochemical features. This new classification does not
      require a routine ultrastructural examination of these tumors. The new definition
      of the Null cell adenoma requires the demonstration of immunonegativity for
      pituitary transcription factors and adenohypophyseal hormones Moreover, the term
      of atypical pituitary adenoma is no longer recommended. In addition to the
      accurate tumor subtyping, assessment of the tumor proliferative potential by
      mitotic count and Ki-67 index, and other clinical parameters such as tumor
      invasion, is strongly recommended in individual cases for consideration of
      clinically aggressive adenomas. This classification also recognizes some subtypes
      of pituitary neuroendocrine tumors as "high-risk pituitary adenomas" due to the
      clinical aggressive behavior; these include the sparsely granulated somatotroph
      adenoma, the lactotroph adenoma in men, the Crooke's cell adenoma, the silent
      corticotroph adenoma, and the newly introduced plurihormonal Pit-1-positive
      adenoma (previously known as silent subtype III pituitary adenoma). An additional
      novel aspect of the new WHO classification was also the definition of the
      spectrum of thyroid transcription factor-1 expressing pituitary tumors of the
      posterior lobe as representing a morphological spectrum of a single nosological
      entity. These tumors include the pituicytoma, the spindle cell oncocytoma, the
      granular cell tumor of the neurohypophysis, and the sellar ependymoma.

PMID- 28766059
TI  - Protective immune response of oral rabies vaccine in stray dogs, corsacs and
      steppe wolves after a single immunization.
AB  - In this study the safety and protective immunity of an oral rabies vaccine, based
      on the live, modified rabies virus strain VRC-RZ2, was examined in stray dogs
      (Canis Sp.), corsacs (Vulpes corsac) and steppe wolves (Canis lupus campestris).
      In the safety group (dogs, n=6; corsacs, n=3; wolves, n=3) which was vaccinated
      with a 10-times field dose/animal, no animals showed any signs of disease or
      changes in behavior or appetite during the period of clinical observation,
      similar to the animals in the negative control group. Saliva samples taken from
      animals prior and post (5th and 10th days) vaccination failed to demonstrate
      rabies virus antigen. Observations of immunogenicity in vaccinated carnivores
      (dogs, corsacs and wolves) during a 180 day period showed the titers of virus
      neutralizing antibodies (VNA) in the blood sera of vaccinated dogs to be within
      0.59-1.37 IU/mL. On 14 days post vaccination (dpv), all the wild carnivores had
      detectable levels of neutralizing antibodies, with mean titers ranging from 0.50
      +/- 0.07 IU/mL (for wolves) to 0.59 +/- 0.10 IU/mL (for corsacs). Weeks after
      vaccination, all the vaccinated wolves and corsacs had higher levels of
      neutralizing antibodies: 0.70 +/- 0.10 - 0.71 +/- 0.08 IU/mL at 30 dpv, 1.06 +/-
      0.08 - 1.28 +/- 0.21 IU/mL at 60 dpv and 0.41 +/- 0.09 - 047 +/- 0.06 at 180 dpv.
      The highest level of VNA (?1.0 IU/ml) was detected at 60 dpv, in all vaccinated
      animals. After challenge all vaccinated dogs remained healthy for 180 days.
      Control animals (unvaccinated dogs) developed symptoms of rabies on day 6 post
      administration of a virulent virus and died of rabies on days 11-13. Of note, the
      VNA titers in all the wild carnivores (corsacs and wolves) immunized with VRC-RZ2
      were higher than 0.5 IU/ml (0.59 +/- 0.11 IU/ml), even as early as 14 days post
      vaccination. These, presumably protective, titers of antibodies to rabies virus
      were present in the dogs and wild carnivores examined in this study for at least
      180 days.

PMID- 28766060
TI  - Noroviruses and sapoviruses associated with acute gastroenteritis in pediatric
      patients in Thailand: increased detection of recombinant norovirus GII.P16/GII.13
      strains.
AB  - Enteric caliciviruses, including noroviruses (NoVs) and sapoviruses (SaVs), are
      recognized as important etiologic agents of acute gastroenteritis (AGE) with
      considerable genetic diversity. In order to gain an overview of the molecular
      epidemiology of human NoVs and SaVs in children hospitalized with AGE in Chiang
      Mai, Thailand, a total of 889 fecal specimens were collected from 2012 to 2014
      and screened for NoVs and SaVs. Out of 889 fecal specimens, 154 (17.3%) and 6
      (0.7%) were positive for NoV GII isolates and SaV, respectively. Among the NoV
      GII, 10 different genotypes were identified with genotype GII.4 being predominant
      (103 strains), followed by GII.3 (17 strains), GII.13 (13 strains), GII.1 (7
      strains), GII.6 (7 strains), GII.7 (2 strains), GII.17 (2 strains), and one each
      of GII.2, GII.15, and GII.21 genotypes. It was observed that four variants of NoV
      GII.4 (Den Haag 2006b, Apeldoorn 2007, New Orleans 2009, Sydney 2012) were
      detected from 2012 to 2014. Analysis of partial nucleotide sequences of RdRp and
      VP1 of the emerging NoV GII.13 strains (9 of 13 strains) revealed that they all
      were GII.P16/GII.13 recombinants. In addition, four different genotypes of SaV,
      GI.1 (2 strains), GII.1 (1 strain), GII.4 (2 strains), and GIV.1 (1 strain) were
      detected. The data revealed heterogeneity and a highly dynamic distribution of
      NoV and SaV genotypes circulating in children admitted to hospitals with AGE in
      Chiang Mai, Thailand, during the period of 2012 to 2014.

PMID- 28766061
TI  - Lysophosphatidic acid enhances human umbilical cord mesenchymal stem cell
      viability without differentiation via LPA receptor mediating manner.
AB  - Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential stromal
      cells which are regarded as the most feasible stem cell group in cell therapy.
      The maintenance of cell survival without differentiation is important in cell
      transplantation and stem cell therapy. However, negative factors exist in cell
      transplantation. Lysophosphatidic acid (LPA) is a non-antigenic small molecule
      phospholipid which induced several fundamental cellular responses, such as cell
      proliferation, apoptosis and migration. In this study we aimed to explore the
      effects of LPA on the survival and differentiation of MSCs and its availability
      in cell therapy. We found that LPA stimulated hUC-MSC proliferation and protected
      hUC-MSCs from lipopolysaccharide (LPS) induced apoptosis. We also observed that
      CD29, CD44, CD73, CD90 and CD105 were expressed, whereas CD34 and CD45 were not
      expressed in hUC-MSCs, and these makers have no change in LPA containing medium,
      which indicated that LPA accelerated the survival of hUC-MSCs in an
      undifferentiating status. We also demonstrated that higher expressed LPAR1
      involved in LPA stimulated cell survival action. LPA stimulated cell
      proliferation was associated with LPAR1 mediated Gi/o-proteins/ERK1/2 pathway. On
      the other hand, LPA protected hUC-MSCs from LPS-induced apoptosis through
      suppressing caspase-3 activation by LPAR1 coupled with a G protein, but not Gi/o
      or Gq/11 in hUC-MSC. Collectively, this study demonstrated that LPA increased the
      proliferation and survival of hUC-MSCs without differentiation through LPAR1
      mediated manner. Our findings provide that LPA as a anti-apoptotic agent having
      potential application prospect in cell transplantation and stem cell therapy.

PMID- 28766063
TI  - Host Responses to Pathogen Priming in a Natural Songbird Host.
AB  - Hosts in free-living populations can experience substantial variation in the
      frequency and dose of pathogen exposure, which can alter disease progression and
      protection from future exposures. In the house finch-Mycoplasma gallisepticum
      (MG) system, the pathogen is primarily transmitted via bird feeders, and some
      birds may be exposed to frequent low doses of MG while foraging. Here we
      experimentally determined how low dose, repeated exposures of house finches to MG
      influence host responses and protection from secondary high-dose challenge. MG
      naive house finches were given priming exposures that varied in dose and total
      number. After quantifying host responses to priming exposures, all birds were
      given a secondary high-dose challenge to assess immunological protection. Dose,
      but not the number of exposures, significantly predicted both infection and
      disease severity following priming exposure. Furthermore, individuals given
      higher priming doses showed stronger protection upon secondary, high-dose
      challenge. However, even single low-dose exposures to MG, a proxy for what some
      birds likely experience in the wild while feeding, provided significant
      protection against a high-dose challenge. Our results suggest that bird feeders,
      which serve as sources of infection in the wild, may in some cases act as
      "immunizers," with important consequences for disease dynamics.

PMID- 28766064
TI  - A Severe Ranavirus Outbreak in Captive, Wild-Caught Box Turtles.
AB  - A Ranavirus outbreak in a captive population of wild-caught individuals was
      monitored using clinical evaluations and real-time PCR in 317 wild box turtles
      held in captivity during translocation. During the 2-year study period, the
      population experienced 71.6% mortality, suggesting that ranaviruses can rapidly
      attenuate populations. Wide variation in infection rate (7-94% per sampling
      period) was observed, which may have been driven by clearing and reinfection,
      adaptive immunity, or imperfect detection using noninvasive samples. Only nasal
      clinical signs were significantly related to infection status, and agreement
      among sample types was low. Subsequent to the initial outbreak, low mortality but
      high real-time PCR prevalence of Ranavirus was observed, suggesting that
      surviving individuals might be tolerant.

PMID- 28766065
TI  - Body temperatures of hibernating little brown bats reveal pronounced behavioural
      activity during deep torpor and suggest a fever response during white-nose
      syndrome.
AB  - Hibernating animals use torpor [reduced body temperature (T b) and metabolic
      rate] to reduce energy expenditure during winter. Periodic arousals to normal T b
      are energetically expensive, so hibernators trade off arousal benefits against
      energetic costs. This is especially important for bats with white-nose syndrome
      (WNS), a fungal disease causing increased arousal frequency. Little brown bats
      (Myotis lucifugus) with WNS show upregulation of endogenous pyrogens and sickness
      behaviour. Therefore, we hypothesized that WNS should cause a fever response
      characterized by elevated T b. Hibernators could also accrue some benefits of
      arousals with minimal T b increase, thus avoiding full arousal costs. We compared
      skin temperature (T sk) of captive Myotis lucifugus inoculated with the WNS
      causing fungus to T sk of sham-inoculated controls. Infected bats re-warmed to
      higher T sk during arousals which is consistent with a fever response. Torpid T
      sk did not differ. During what we term "cold arousals", bats exhibited movement
      following T sk increases of only 2.2 +/- 0.3  degrees C, compared to >20  degrees
      C increases during normal arousals. Cold arousals occurred in both infected and
      control bats, suggesting they are not a pathophysiological consequence of WNS.
      Fever responses are energetically costly and could exacerbate energy limitation
      and premature fat depletion for bats with WNS. Cold arousals could represent an
      energy-saving mechanism for both healthy and WNS-affected bats when complete
      arousals are unnecessary or too costly. A few cold arousals were observed mid
      hibernation, typically in response to disturbances. Cold arousals may, therefore,
      represent a voluntary restriction of arousal temperature instead of loss of
      thermoregulatory control.

PMID- 28766066
TI  - Outcome of kidney transplantation in pediatric patients with ANCA-associated
      glomerulonephritis: a single-center experience.
AB  - OBJECTIVES: Data on kidney transplant outcomes for pediatric patients with end
      stage renal disease (ESRD) secondary to anti-neutrophil cytoplasmic antibody
      glomerulonephritis (ANCA GN), particularly granulomatosis with polyangiitis (GPA)
      and microscopic polyangiitis (MPA), is limited. We describe our experience of
      kidney transplantation in pediatric ANCA GN patients. METHODS: We performed a
      retrospective review of patients with ANCA GN who developed ESRD and were
      transplanted at a single center between the years 2000 and 2014. RESULTS: Since
      2000, there were seven pediatric patients with ANCA GN (four MPA) transplanted.
      Mean age at ANCA GN diagnosis was 11.8 +/- 2.8 (range, 7.2-15.4) years. All seven
      were ANCA (three anti-PR3/four anti-MPO) positive. Estimated glomerular
      filtration rate (eGFR) at diagnosis was 11.7 +/- 6.3 ml/min/1.73 m2. All received
      steroids and cyclophosphamide and three (23.3%) received plasma exchange. Six
      were dialysis dependent by 6 months post diagnosis. Time from diagnosis to
      transplant was 30 +/- 12 (range, 17-48) months. Six of the seven received a
      deceased donor transplant. All patients received induction therapy and standard
      maintenance immunosuppression post transplant. Median duration of follow-up post
      transplantation was 27 months (range, 13-88 months). Median eGFR at last follow
      up was 77 ml/min/1.73 m2 (range, 7.9-83.5). One patient lost her transplant to
      acute cellular rejection following non-adherence to immunosuppression after 21
      months of stable transplant function. No patient had recurrence of vasculitis,
      either renal or extra-renal. CONCLUSIONS: Short-term patient and allograft
      survival in pediatric patients with ESRD secondary to ANCA GN seems excellent,
      with no recurrence of vasculitis post transplant in this small cohort.

PMID- 28766067
TI  - Cementless total hip arthroplasty in the treatment after acetabular fractures.
AB  - INTRODUCTION: The outcomes of total hip arthroplasty (THA) for the treatment of
      posttraumatic arthritis after acetabular fractures were inferior to those after
      primary non-traumatic THA. METHODS: This study was performed in academic level I
      trauma center. From January 2011 to December 2014, a consecutive series of 21
      patients (9 females), with average age of 56.7 years (range 29-75 years) who had
      posttraumatic hip joint arthritis after acetabular fractures, were included in
      our study. All patients underwent cementless THA. The average duration of follow
      up was 26 months (range 24-36 months). RESULTS: At the latest follow-up, all
      patients could walk independently, thirteen (62%) patients had excellent Harris
      hip score, five (24%) had good HHS, and 3 (14%) had fair score. WOMAC scale
      decreased from 63 (range 42-92) to 4 (range 0-19). Two patients (9.5%) had
      heterotopic bone formation which did not affect the activity of the patients.
      There were no signs of loosening of the acetabular cups or around the femoral
      stem. CONCLUSION: Cementless THA is an ideal treatment for posttraumatic hip
      arthritis with anatomic restoration of the hip center to improve the functional
      results and decrease the incidence of complications and revision rate.

PMID- 28766068
TI  - Pediatric soft tissue sarcoma of the limbs: clinical outcome of 97 patients.
AB  - PURPOSE: Soft tissue sarcomas (STS) of the extremities in children are a
      heterogeneous group of tumors with a very different prognosis for which optimal
      treatment remains controversial. PATIENTS AND METHODS: We retrospectively
      evaluated 97 patients younger than 15 years old affected by limb soft tissue
      sarcomas. All cases were histologically revised, and tumor grade was assessed
      according to the FNLCC system. Thirty-two were rhabdomyosarcoma (RMS) and 65 non
      rhabdomyosarcoma (NRMSTS); among these, 40 (61.5%) were grade 3 according to
      FNLCC classification. Overall survival, local recurrence and distant metastasis
      were analyzed. RESULTS: Overall survival was 77.8% at 5 years and 69.7% at 10
      years. Among grade 3 tumors, RMS had a worse prognosis over NRSTS. Similarly,
      tumors larger than 5 cm had a worse prognosis compared to smaller ones. Local
      recurrence-free survival was 90.7% at 5 years and 87.1% at 10 years with a better
      local control in grade 3 NRSTS over RMS and in tumors smaller than 2 cm.
      CONCLUSION: Children affected by extremities RMS were confirmed to have the worst
      prognosis, in particular in case of metastasis at presentation. Differently from
      adult patients, hand and feet locations are frequent site for STS and 2 cm
      diameter should be taken as cut off for higher risk of LR. Similarly to adulthood
      STS, grading correlates with prognosis in NRSTS. The identification of prognostic
      variables should enable risk-adapted therapies to be planned.

PMID- 28766069
TI  - Platelet-rich plasma versus exchange intramedullary nailing in treatment of long
      bone oligotrophic nonunions.
AB  - INTRODUCTION: The aim of the study was to evaluate the effects of platelet-rich
      plasma on healing rates and healing time in the treatment of long bone nonunions
      treated by an intramedullary nail previously. MATERIALS AND METHODS: Between
      August 2008 and January 2012, 14 consecutive patients who were treated for long
      bone nonunions with percutaneous platelet-rich plasma application (PRP) were
      included in the study. The control group included 15 consecutive patients who
      were treated with exchange intramedullary nailing (EIN). In the postoperative
      period, all patients were controlled in every 2 weeks clinically and in every 4
      weeks radiologically. Patients were evaluated with visual analog scale (VAS) in
      preoperative and postoperative periods. RESULTS: The mean healing time was
      shorter in PRP group as 16.71 +/- 2.4 weeks compared with that of 19.07 +/- 3.67
      weeks in EIN group (p = 0.053). At the end of the follow-up, the union is
      achieved in 92.8% of the cases in PRP group. This ratio was 80% in control group.
      The mean VAS values in preoperative and postoperative periods were not
      statistically significant in both groups (p > 0.05). When PRP and control groups
      were evaluated individually, the postoperative VAS was lower than that of
      preoperative VAS in both groups (p = 0.0001 and p = 0.0001, respectively).
      CONCLUSION: Percutaneous PRP application significantly affected union rate, but
      no significant difference found when compared to EIN in the treatment of
      oligotrophic nonunions after intramedullary nailing of long bone fractures. PRP
      can be applied as a minimally invasive and safe method of saving resources in
      medical care instead of EIN.

PMID- 28766071
TI  - Erratum to: Inaugural Conference on Incorporating Patient-Reported Outcomes and
      Patient Preference Information into Clinical Research, Clinical Care, and Risk
      Benefit Assessments for Neurodegenerative Diseases.

PMID- 28766070
TI  - Prothrombin time-international normalized ratio is a useful marker for edoxaban
      efficacy in preventing venous thromboembolism after total knee arthroplasty.
AB  - BACKGROUND: Deep vein thrombosis (DVT) is one of the main complications following
      total knee arthroplasty (TKA). In this study, oral administration of 15 mg
      edoxaban (a factor Xa inhibitor) once daily for 14 days efficiently prevented the
      incidence of DVT. Our hypothesis was that prothrombin time-international
      normalized ratio (PT-INR) on the third postoperative day could predict the
      incidence of DVT following TKA. METHODS: In this study, 286 subjects were
      enrolled and divided into two groups according to the presence or absence of DVT.
      Several variables [age, body mass index, postoperative D-dimer level, PT-INR, and
      functional recovery findings (standing)] were analysed to determine the
      predictors of DVT, and for DVT diagnosis, ultrasonography was performed for seven
      days after surgery. RESULTS: The PT-INR levels were significantly higher in the
      group that did not develop DVT (p = 0.01). Further analysis with logistic
      regression analysis and receiver operating characteristic curve was performed.
      The PT-INR on the third postoperative day was an independent factor of the
      incidence of DVT (odds ratio 0.210; p = 0.035). The cut-off PT-INR was calculated
      to be 1.425. CONCLUSION: PT-INR level is a useful marker in determining whether
      15 mg edoxaban administration can prevent DVT after TKA. It is suggested that
      increment of edoxaban to control PT-INR over the cut-off point might prevent the
      incidence of DVT.

PMID- 28766072
TI  - Advanced training in reproductive psychiatry: The case for standardization in
      training and a path to sub-specialty recognition.

PMID- 28766073
TI  - Does an early postpartum Edinburgh Postnatal Depression Scale (EPDS) really
      detect the majority of women with elevated EPDS scores at 16-weeks postpartum?

PMID- 28766074
TI  - Missed the take-home message.

PMID- 28766075
TI  - Protein binding hot spots prediction from sequence only by a new ensemble
      learning method.
AB  - : Hot spots are interfacial core areas of binding proteins, which have been
      applied as targets in drug design. Experimental methods are costly in both time
      and expense to locate hot spot areas. Recently, in-silicon computational methods
      have been widely used for hot spot prediction through sequence or structure
      characterization. As the structural information of proteins is not always solved,
      and thus hot spot identification from amino acid sequences only is more useful
      for real-life applications. This work proposes a new sequence-based model that
      combines physicochemical features with the relative accessible surface area of
      amino acid sequences for hot spot prediction. The model consists of 83
      classifiers involving the IBk (Instance-based k means) algorithm, where instances
      are encoded by important properties extracted from a total of 544 properties in
      the AAindex1 (Amino Acid Index) database. Then top-performance classifiers are
      selected to form an ensemble by a majority voting technique. The ensemble
      classifier outperforms the state-of-the-art computational methods, yielding an F1
      score of 0.80 on the benchmark binding interface database (BID) test set.
      AVAILABILITY: http://www2.ahu.edu.cn/pchen/web/HotspotEC.htm .

PMID- 28766076
TI  - Multicenter analysis of risk factors for anastomotic leakage after middle and low
      rectal cancer resection without diverting stoma: a retrospective study of 319
      consecutive patients.
AB  - PURPOSE: The purpose of this study was to evaluate the risk factors for
      anastomotic leakage (AL) after anterior resection for middle and low rectal
      cancer in order to help surgeons to decide which patients could benefit from a
      diverting stoma. METHODS: Data on 319 patients having a middle and low rectal
      cancer resection with anastomosis between May 2011 and October 2015 from two
      hospitals were included in the study. The analysis included the following
      variables: patient-related variables (gender, age, diabetes mellitus, ASA score,
      preoperative radiochemotherapy, body mass index, blood hemoglobin, and serum
      albumin level), tumor-related variables (K-ras status, distance of tumor from the
      anal verge, histopathologic grade, pathological T stage, pathological N stage,
      pathological M stage, TNM stage, and tumor size), and surgery-related variables
      (laparoscopic or open surgery, blood loss, and operative time). Univariate and
      multivariate regression analysis were carried out to identify risk factors for
      AL. RESULTS: The AL rate was 11.91% (38/319). Male (OR 2.898, 95% CI 1.265-6.637,
      p = 0.012), diabetes mellitus (OR 2.482, 95% CI 1.004-6.134, p = 0.049), K-ras
      mutation (OR 2.544, 95% CI 1.210-5.348, p = 0.014), distance of tumor from the
      anal verge (OR 3.445, 95% CI 1.631-7.279, p = 0.001), and preoperative
      radiochemotherapy (OR 2.790, 95% CI 1.056-7.372, p = 0.039) were independent risk
      factors of AL. One (2.63%) in 38 patients with AL presented with no risk factor
      of AL, 6 (15.8%) in 38 patients with 1 risk factor, 16 (42.1%) in 38 patients
      with 2 risk factors, 9 (23.7%) in 38 patients with 3 risk factors, and 6 (15.7%)
      in 38 patients with 4 risk factors. No patient with 5 risk factors in our study.
      AL rate increased with the elevated number of risk factors clustering in
      individuals. CONCLUSIONS: K-ras mutation is first reported to be an independent
      risk factor for AL after sphincter-preserving surgery without diverting stoma. A
      diverting stoma should be performed in sphincter-preserving surgery for middle
      and low rectal cancer patients with 2 or more risk factors identified in this
      analysis.

PMID- 28766078
TI  - Double pituitary adenomas are most commonly associated with GH- and ACTH
      secreting tumors: systematic review of the literature.
AB  - INTRODUCTION: Double adenomas in the pituitary gland are a rare occurrence. The
      ability to cure a hormone-producing adenoma with surgery is dependent on the
      ability to identify and completely remove the correct adenoma. The relative
      frequency of each subtype of hormone-secreting adenomas confirmed with magnetic
      resonance image (MRI), surgery and immunohistochemistry is not defined. METHODS:
      Following PRISMA guidelines, we performed a systematic review of PubMed Central,
      Google Scholar, Scopus Database, Cochrane database and Science Research, using
      the key-words: "double pituitary adenomas", "multiple pituitary adenomas" and
      only papers where multiple or truly separate double pituitary adenomas were
      identified pre-surgically by MRI and/or confirmed by
      pathology/immunohistochemistry staining were included. RESULTS: We reviewed
      papers from 1975 to 2016 and found 17 cases with two pituitary adenomas and 1
      with three pituitary adenomas. The ages ranged from 22 to 67 years old, and there
      were twelve females and five males. Immunohistochemical staining showed that the
      most common double pituitary adenomas were growth hormone (GH)- followed by
      adrenocorticotropic (ACTH)-secreting. CONCLUSION: Double pituitary adenomas are
      rare but most commonly found with GH- or ACTH-producing tumors. It is critical to
      remove all identified possible adenomas to achieve biochemical cure and
      clinicians should have heightened sensitivity in patients with acromegaly or
      Cushing's Disease.

PMID- 28766079
TI  - Lawful Sinners: Reproductive Governance and Moral Agency Around Abortion in
      Mexico.
AB  - The Catholic Hierarchy unequivocally bans abortion, defining it as a mortal sin.
      In Mexico City, where the Catholic Church wields considerable political and
      popular power, abortion was recently decriminalized in a historic vote. Of the
      roughly 170,000 abortions that have been carried out in Mexico City's new public
      sector abortion program to date, more than 60% were among self-reported Catholic
      women. Drawing on eighteen months of fieldwork, including interviews with 34
      Catholic patients, this article examines how Catholic women in Mexico City
      grapple with abortion decisions that contravene Church teachings in the context
      of recent abortion reform. Catholic women consistently leveraged the local
      cultural, economic, and legal context to morally justify their abortion decisions
      against church condemnation. I argue that Catholic women seeking abortion resist
      religious injunctions on their reproductive behavior by articulating and
      asserting their own moral agency grounded in the contextual dimensions of their
      lives. My analysis informs conversations in medical anthropology on moral
      decision-making around reproduction and on local dynamics of resistance to
      reproductive governance. Moreover, my findings speak to the deficiencies of a
      feminist vision focused narrowly on fertility limitation, versus an expanded
      framework of reproductive justice that considers as well the need for conditions
      of income equality and structural supports to facilitate reproduction and
      parenting among women who desire to keep their pregnancies.

PMID- 28766080
TI  - Trajectories in quality of life of patients with a fracture of the distal radius
      or ankle using latent class analysis.
AB  - PURPOSE: This prospective study aimed to identify the different trajectories of
      quality of life (QOL) in patients with distal radius fractures (DRF) and ankle
      fractures (AF). Secondly, it was examined if subgroups could be characterized by
      sociodemographic, clinical, and psychological variables. METHODS: Patients (n =
      543) completed the World Health Organization Quality of Life assessment
      instrument-Bref (WHOQOL-Bref), the pain, coping, and cognitions questionnaire,
      NEO-five factor inventory (neuroticism and extraversion), and the state-trait
      anxiety inventory (short version) a few days after fracture (i.e., pre-injury QOL
      reported). The WHOQOL-Bref was also completed at three, six, and 12 months post
      fracture. Latent class trajectory analysis (i.e., regression model) including the
      Step 3 method was performed in Latent Gold 5.0. RESULTS: The number of classes
      ranged from three to five for the WHOQOL-Bref facet and the four domains with a
      total variance explained ranging from 71.6 to 79.4%. Sex was only significant for
      physical and psychological QOL (p < 0.05), whereas age showed significance for
      overall, physical, psychological, and environmental QOL (p < 0.05). Type of
      treatment or fracture type was not significant (p > 0.05). Percentages of chronic
      comorbidities were 1.8 (i.e., social QOL) to 4.5 (i.e., physical QOL) higher in
      the lowest compared to the highest QOL classes. Trait anxiety, neuroticism,
      extraversion, pain catastrophizing, and internal pain locus of control were
      significantly different between QOL trajectories (p < 0.05). CONCLUSIONS: The
      importance of a biopsychosocial model in trauma care was confirmed. The different
      courses of QOL after fracture were defined by several sociodemographic and
      clinical variables as well as psychological characteristics. Based on the
      identified characteristics, patients at risk for lower QOL may be recognized
      earlier by health care providers offering opportunities for monitoring and
      intervention.

PMID- 28766081
TI  - Causal effects of informal care and health on falls and other accidents among the
      elderly population in China.
AB  - PURPOSE: This article analyzes the causal effects of informal care, mental
      health, and physical health on falls and other accidents (e.g., traffic
      accidents) among elderly people. We also examine if there are heterogeneous
      impacts on elderly of different gender, urban status, and past accident history.
      METHODS: To purge potential reversal causal effects, e.g., past accidents induce
      more future informal care, we use two-stage least squares to identify the
      impacts. We use longitudinal data from a representative national China Health and
      Retirement Longitudinal Study of people aged 45 and older in China. A total of
      3935 respondents with two-wave data are included in our study. Each respondent is
      interviewed to measure health status and report their accident history. Mental
      health is assessed using CES-D questions. RESULTS: Our findings indicate that
      while informal care decreased the occurrence of accidents, poor health conditions
      increase the occurrence of accidents. We also find heterogeneous impacts on the
      occurrence of accidents, varying by gender, urban status, and past accident
      history. CONCLUSIONS: Our findings suggest the following three policy
      implications. First, policy makers who aim to decrease accidents should take
      informal care of elders into account. Second, ease of birth policy and postponed
      retirement policy are urgently needed to meet the demands of informal care.
      Third, medical policies should attach great importance not only to physical
      health but also mental health of elderly parents especially for older people with
      accident history.

PMID- 28766082
TI  - Quality of life among German parents of children with cystic fibrosis: the
      effects of being a single caregiver.
AB  - PURPOSE: Quality of life (QoL) has not been studied up to now in single parents
      of children with cystic fibrosis (CF). We hypothesized lower QoL compared to
      parents living together with a partner. We explored whether single parents
      benefit in a comparable manner from a family-oriented inpatient rehabilitation
      (FOR) program provided in Germany. METHODS: 260 parents of a child with CF (0-17
      years), 40 of them single parents, were included. Their QoL was compared to
      partnered parents using Student's t test for independent samples. The positive
      impact of the FOR program on parents' QoL was examined in a subgroup of n = 56
      parents using a 2 * 2 analysis of variance with repeated measures on discharge
      and 6 months later. RESULTS: Single parents reported significantly lower QoL (M =
      54.89; SD = 12.44) than partnered parents (M = 61.55; SD = 15.43; t(258) = 
      2.581; p = .010). Age of the child or employment status did not impact that
      difference. In the short term they benefit less from a FOR program than partnered
      parents (group * time effect: F(1) = 4.832; p = .032), but this was no longer the
      case at the 6-month follow-up (group * time effect: F(1) = 1.443; p = .235).
      CONCLUSIONS: Single parents are at risk of lower QoL. CF care teams should help
      these parents in particular when it comes to accessing social support.

PMID- 28766083
TI  - Do male esophageal cancer patients have impaired sexual function after
      esophagectomy? A self-reported outcomes study.
AB  - PURPOSE: Sexual function is a significant part of patients' quality of life,
      which is another important aspect of cancer. This study assessed and compared the
      sexual function of male esophageal cancer patients to that of age-matched normal
      controls through postoperative follow-up surveys. METHODS: The study included 105
      male esophageal cancer patients aged 38-81 years who underwent a curative-intent
      esophagectomy between April 2012 and May 2014. This observational study included
      sociodemographic and clinicopathological characteristics and responses to sexual
      function questionnaires International Index of Erectile Function (IIEF) at 6 and
      12 months after surgery. An age-matched normal control group was recruited. Non
      parametric tests were used when appropriate. RESULTS: The median patient age was
      59 years. The factors significantly associated with sexual dysfunction on the 6
      month survey included older age, and postoperative complications. At 12 months
      after surgery, older age was significantly associated with poorer sexual
      function. The sexual function scores significantly increased from 6 to 12 months
      after surgery (P < 0.05); there was no difference in the patients' 12-month
      sexual function scores and those of the normal controls (P > 0.05). Notably,
      compared to older patients (age >=60 years), the younger (age <60 years) patients
      reported a significantly better sexual function scores (P < 0.05). CONCLUSIONS:
      Age, and postoperative complications were the factors significantly associated
      with sexual function. Impaired sexual function after primary treatment can be
      recovered in male esophageal cancer patients; younger patients may regain sexual
      function better than their older counterparts.

PMID- 28766084
TI  - Comparison of the EQ-5D-3L and the SF-6D (SF-12) contemporaneous utility scores
      in patients with cardiovascular disease.
AB  - PURPOSE: Multi-attribute utility instruments (MAUIs) are widely used to measure
      utility weights. This study sought to compare utility weights of two popular
      MAUIs, the EQ-5D-3L and the SF-6D, and inform researchers in the selection of
      generic MAUI for use with cardiovascular (CVD) patients. METHODS: Data were
      collected in the Young@Heart study, a randomised controlled trial of a nurse-led
      multidisciplinary home-based intervention compared to standard usual care.
      Participants (n = 598) completed the EQ-5D-3L and the SF-12v2, from which the SF
      6D can be constructed, at baseline and at 24-month follow-up. This study examined
      discrimination, responsiveness, correlation and differences across the two
      instruments. RESULTS: Both MAUIs were able to discriminate between the NYHA
      severity classes and recorded similar changes between the two time points
      although only SF-6D differences were significant. Correlations between the
      dimensions of the two MAUIs were low. There were significant differences between
      the two instruments in mild conditions but they were similar in severe
      conditions. Substantial ceiling and floor effects were observed. CONCLUSIONS: Our
      findings indicate that the EQ-5D and the SF-6D cover different spaces in health
      due to their classification systems. Both measures were capable of discriminating
      between severity groups and responsive to quality of life changes in the follow
      up. It is recommended to use the EQ-5D-3L in severe and the SF-6D in mild CVD
      conditions.

PMID- 28766085
TI  - Influence of sex, menstrual cycle, and oral contraceptives on the cerebrovascular
      response to paced deep breathing.
AB  - PURPOSE: Deep breathing assesses autonomic function; however, many
      researchers/clinicians do not account for hyperventilation, brain blood flow or
      blood pressure. METHODS: Men and women (with/without oral contraceptives)
      participated. women participated during low and high hormone phases of the
      menstrual cycle. Blood pressure, end-tidal carbon dioxide, middle cerebral artery
      velocity and cerebrovascular resistance were assessed. RESULTS: Deep breathing
      decreased end-tidal carbon dioxide and middle cerebral artery velocity while
      increasing cerebrovascular resistance in all participants; blood pressure
      decreased in men. There were no influences of menstrual cycle or oral
      contraceptives. CONCLUSIONS: Men have different autonomic responses to deep
      breathing compared to women.

PMID- 28766087
TI  - [Dorsal atlantoaxial stabilization using the Goel-Harms technique].

PMID- 28766086
TI  - Anti-inflammatory evaluation and characterization of leaf extract of Ananas
      comosus.
AB  - Ananas comosus (L.) Merr (Pineapple) is a tropical plant with an edible fruit. In
      the present study, the potential anti-inflammatory activity of A. comosus leaf
      extract (ALE) was studied. ALE prepared using soxhlet apparatus was subjected to
      preliminary qualitative phytochemical analysis and quantitative estimations of
      flavonoids and tannins. The components present in ALE were identified using
      liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass
      spectrometry (GC-MS). Inhibitory effects of ALE on protein denaturation, and
      proteinase activity were assessed. Its effect on secretion of pro-inflammatory
      cytokines and inflammatory mediators by lipopolysaccharide-stimulated macrophages
      was also analyzed. Further, its anti-inflammatory activity in carrageenan-induced
      inflammatory rat model was examined. The preliminary qualitative phytochemical
      analysis revealed presence of flavonoids, phenols, tannins, carbohydrates,
      glycosides, and proteins in the extract. Total flavonoids and total tannins were
      0.17 +/- 0.006 mg equivalent of quercetin/g of ALE and 4.04 +/- 0.56 mg
      equivalent of gallic acid/g of ALE. LC-MS analysis identified the presence of 4
      hydroxy pelargonic acid, 3,4,5-trimethoxycinnamic and 4-methoxycinnamic acid,
      whereas GC-MS analysis identified the presence of campesterol and ethyl
      isoallocholate that have been previously reported for anti-inflammatory activity.
      ALE showed significant inhibition of protein denaturation and proteinase activity
      and also controlled secretion of tumour necrosis factor-alpha, interleukin-1beta
      and prostaglandins, as well as the generation of reactive oxygen species by
      activated macrophages. ALE also significantly decreased carrageenan-induced acute
      paw edema. The study, therefore, identified the components present in ALE that
      may be responsible for its anti-inflammatory activity and thus demonstrated its
      potential use against acute inflammatory diseases.

PMID- 28766088
TI  - Synthesis of disaccharides using beta-glucosidases from Aspergillus niger, A.
      awamori and Prunus dulcis.
AB  - OBJECTIVE: Glucose conversion into disaccharides was performed with beta
      glucosidases from Prunus dulcis (beta-Pd), Aspergillus niger (beta-An) and A.
      awamori (beta-Aa), in reactions containing initial glucose of 700 and 900 g l-1.
      RESULTS: The reactions' time courses were followed regarding glucose and product
      concentrations. In all cases, there was a predominant formation of gentiobiose
      over cellobiose and also of oligosaccharides with a higher molecular mass. For
      reactions containing 700 g glucose l-1, the final substrate conversions were 33,
      38, and 23.5% for beta-An, beta-Aa, and beta-Pd, respectively. The use of beta-An
      yielded 103 g gentiobiose l-1 (15.5% yield), which is the highest reported for a
      fungal beta-glucosidase. The increase in glucose concentration to 900 g l-1
      resulted in a significant increase in disaccharide synthesis by beta-Pd, reaching
      128 g gentiobiose l-1 (15% yield), while for beta-An and beta-Aa, there was a
      shift toward the synthesis of higher oligosaccharides. CONCLUSION: beta-Pd and
      the fungal beta-An and beta-Aa beta-glucosidases present quite dissimilar
      kinetics and selective properties regarding the synthesis of disaccharides; while
      beta-Pd showed the highest productivity for gentiobiose synthesis, beta-An
      presented the highest specificity.

PMID- 28766089
TI  - Reweighted estimators for additive hazard model with censoring indicators missing
      at random.
AB  - Survival data with missing censoring indicators are frequently encountered in
      biomedical studies. In this paper, we consider statistical inference for this
      type of data under the additive hazard model. Reweighting methods based on simple
      and augmented inverse probability are proposed. The asymptotic properties of the
      proposed estimators are established. Furthermore, we provide a numerical
      technique for checking adequacy of the fitted model with missing censoring
      indicators. Our simulation results show that the proposed estimators outperform
      the simple and augmented inverse probability weighted estimators without
      reweighting. The proposed methods are illustrated by analyzing a dataset from a
      breast cancer study.

PMID- 28766090
TI  - What Do Pediatricians Tell Parents About Bed-Sharing?
AB  - Background and objectives Despite the risks of bed-sharing, little is known about
      what pediatricians tell parents about bed-sharing with infants and whether
      pediatricians provide specific recommendations outlined by the American Academy
      of Pediatrics (AAP). This study aimed to understand pediatricians' opinions about
      bed-sharing and the advice pediatricians provide to parents about bed sharing.
      Methods The study employed a qualitative study design and the conceptual
      framework of the Theory of Planned Behavior. 24 primary care pediatricians from a
      variety of practice settings were interviewed about the anticipatory guidance
      they provide to families whose infants are in the at-risk age group for SIDS.
      Results Pediatricians' opinions about bed-sharing differed widely both with
      respect to identifying bed-sharing as a topic they routinely address in
      anticipatory guidance as well as in what they tell parents about bed sharing.
      Some strongly and routinely advise against bed-sharing and identify bed-sharing
      as a clear risk to infants. Others believe bed-sharing to be both safe and
      useful. A third group allow the content of anticipatory guidance to be driven by
      parental concerns. Most pediatricians are clearer in their recommendation to
      place infants supine to sleep than in their recommendation to avoid bed-sharing.
      Conclusions Overall, there is considerable variation among pediatricians in the
      advice they provide about bed-sharing, and most advice is not congruent with the
      AAP recommendations. Additional efforts to educate pediatricians may be necessary
      to change attitudes and behaviors with respect to anticipatory guidance about
      safe sleep.

PMID- 28766091
TI  - Maximizing Opportunities: Family Planning and Maternal, Infant, and Young Child
      Nutrition Integration in Bondo Sub-County, Kenya.
AB  - Purpose This article shares learning from an innovative demonstration program
      integrating maternal, infant, and young child nutrition (MIYCN) and family
      planning (FP) services in western Kenya, providing recommendations for future
      work to expand MIYCN and FP integration. Description Six health facilities
      reorganized to integrate MIYCN and FP services and community health volunteers
      (CHVs) promoted MIYCN and FP in adjacent communities in Bondo Sub-County over a 1
      year period. At the facility level, each provider was directed to provide both
      sets of services in a single room during FP, antenatal care, postnatal care, or
      child consultation visits (a "one stop shop" approach). At community level, CHVs
      were to conduct household visits equipped with new integrated materials and
      incorporate MIYCN and FP within community activities. Assessment Although the
      "one stop shop" approach, where one provider offers all integrated services in
      one room, was initially proposed for all facilities, this worked most effectively
      in the dispensary and health centers. The sub-county hospital adapted the
      approach such that integrated services were offered by more than one provider
      during a visit, with clients linked from one provider to another through same-day
      intra-facility referrals. CHVs were generally able to incorporate MIYCN and FP
      content within household visits and community activities; however some knowledge
      gaps were noted after initial training, necessitating additional refresher
      training. Conclusion This demonstration experience revealed that future
      replication efforts should enable sub-county team leadership, assess facility
      readiness, streamline data collection, build local buy-in, and prioritize
      dispensaries and health centers with high client loads.

PMID- 28766092
TI  - Facilitators and Barriers to Disclosure of Postpartum Mood Disorder Symptoms to a
      Healthcare Provider.
AB  - Objectives This study explored perceived barriers and facilitators to disclosure
      of postpartum mood disorder (PPMD) symptoms to healthcare professionals among a
      community-based sample. Methods A sample of predominantly white, middle class,
      partnered, adult women from an urban area in the southeast United States (n =
      211) within 3 years postpartum participated in an online survey including the
      Perceived Barriers to Treatment Scale, the Maternity Social Support Scale, the
      Depression, Anxiety and Stress Scales-21, and items querying PPMD disclosure.
      Perceived barriers were operationalized as factors, from the patient's
      perspective, that impede or reduce the likelihood of discussing her postpartum
      mood symptoms with a healthcare provider. Analyses examined: (1) characteristics
      associated with perceived barriers; (2) characteristics associated with perceived
      social support; and (3) characteristics, perceived barriers, and perceived social
      support as predictors of disclosure. Results Over half of the sample reported
      PPMD symptoms, but one in five did not disclose to a healthcare provider.
      Approximately half of women reported at least one barrier that made help-seeking
      "extremely difficult" or "impossible." Over one-third indicated they had less
      than adequate social support. Social support and stress, but not barriers, were
      associated with disclosure in multivariable models. Conclusions for Practice Many
      women experiencing clinically-significant levels of distress did not disclose
      their symptoms of PPMD. Beyond universal screening, efforts to promote PPMD
      disclosure and help-seeking should target mothers' social support networks.

PMID- 28766093
TI  - Breastfeeding and Exposure to Past, Current, and Neighborhood Violence.
AB  - Objectives Breastfeeding has short- and long-term health benefits for children
      and mothers, but US breastfeeding rates are suboptimal. Exposure to violence may
      contribute to these low rates, which vary by race/ethnicity. We studied: (1)
      whether patterns of violence exposure differ by race/ethnicity and (2) whether
      these patterns are associated with breastfeeding outcomes. Methods We conducted a
      secondary analysis of data drawn from self-report surveys completed by a
      convenience sample of low-income postpartum women (n = 760) in upstate New York.
      Latent class analysis was used to identify groups of women with similar responses
      to seven violence measures, including childhood physical and/or sexual violence,
      experience of partner violence during or just after pregnancy (physical,
      emotional, verbal), and neighborhood violence (perceived or by ZIP code).
      Logistic regression and survival analysis were utilized to determine if classes
      were associated with breastfeeding initiation, duration, and exclusivity,
      controlling for demographics. Results Exposure to at least one form of violence
      was high in this sample (87%). We identified 4 classes defined by violence
      exposure (combining current and historical exposures). Violence exposure patterns
      differed between racial/ethnic groups, but patterns were inconsistently
      associated with breastfeeding plans or outcomes. For White women, history of
      violence exposure increased the likelihood of earlier breastfeeding cessation. By
      contrast, among Black women, history of violence exposure increased the
      likelihood of having a breastfeeding plan and initiating breastfeeding.
      Conclusions for Practice Some differences between violence exposure classes are
      likely due to the correlation between race/ethnicity and socioeconomic status in
      the community studied. Additional studies are warranted to better understand how
      exposure to violence is related to breastfeeding and how best to support women
      making decisions about intention, initiation, and duration of breastfeeding.

PMID- 28766094
TI  - Risk of Depressive Symptoms Associated with Morbidity in Postpartum Women in
      Rural Bangladesh.
AB  - : Objectives Depression following pregnancy is common, but its extent and
      association with maternal morbidity in the first 6 months postpartum have not
      been well described in low resource settings such as rural Bangladesh. Methods We
      used data from a population-based, community trial of approximately 39,000
      married rural Bangladeshi women aged 13-44 between 2001 and 2007 to examine the
      relation between women's reported morbidity symptoms from childbirth to 3 months
      postpartum, and subsequent depressive symptoms assessed at 6 months postpartum.
      We calculated crude and adjusted risk ratios for depressive symptoms following
      women's reports of reproductive, urinary, neurologic, nutrition and other illness
      measures constructed based on symptomatic reporting. Results In models adjusted
      for sociodemographic factors and co-morbidities, all postpartum illnesses were
      associated with an increased relative risk [RR, with 95% confidence intervals
      (CI) excluding 1] of depressive symptoms by 6 months postpartum. These
      morbidities included uterine prolapse (RR 1.20, 95% CI 1.04-1.39), urinary tract
      infection (RR 1.24, 95% CI 1.11-1.38), stress related incontinence (SRI) (RR
      1.49, 95% 1.33-1.67), simultaneous SRI and continuously dripping urine (RR 1.60
      2.96), headache [RR 1.20 (95% CI 1.12-1.28)], convulsions (RR 1.67, 95%CI 1.36
      2.06), night blindness (RR 1.33, 95% CI 1.19-1.49), anemia (RR 1.38, 95% CI 1.31
      1.46), pneumonia (RR 1.24, 95% CI 1.12-1.37), gastroenteritis (RR 1.24, 95% CI
      1.17-1.31) and hepatobiliary disease (RR 2.10, 96% CI 1.69-2.60). Conclusions for
      Practice Illnesses during the first three postpartum months were risk factors for
      depressive symptoms, with the strongest associations noted for convulsions and
      hepatobiliary disease. Symptoms of depression may be of particular concern among
      women suffering from physical illnesses. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov NCT0019882.

PMID- 28766095
TI  - Signaling interactions predicted by the Tritope model of the TCR.
AB  - As the data accumulates, it becomes obvious that the Standard Model of TCR
      structure-function relationships is in jeopardy. The proposed Tritope model has
      become more meaningful and, in any case, is richer in prediction and explanation.
      This is illustrated here by using the signaling interactions of the TCR as
      examples. An unsuspected signaling pathway for positive selection, and for
      alloreactivity, is predicted. Further, crucial data needed to elucidate the
      structural elements that distinguish signaling for restrictive- versus allo
      reactivity are identified.

PMID- 28766096
TI  - Inhibiting ERK/Mnk/eIF4E broadly sensitizes ovarian cancer response to
      chemotherapy.
AB  - PURPOSE: To investigate whether ERK/MNK/eIF4E contributes chemoresistance in
      ovarian cancer. METHODS: The phosphorylated levels of Erk, Mnk, and eIF4E were
      systematically analyzed in ovarian cancer patients before and after chemotherapy,
      and ovarian cancer cells exposed to short- and long-term chemo-agent treatment.
      The roles of Erk/Mnk/eIF4E were investigated using pharmacological and genetic
      approaches. RESULTS: Increased phosphorylation levels of ERK, Mnk1, and eIF4E
      were observed in ovarian cancer cell exposed to chemotherapeutic agents, and
      paclitaxel-resistant SK-OV-3-r cells, and is a common response of ovarian cancer
      patients undergoing chemotherapy. MEK inhibitor U0126 inhibits basal and
      chemodrug-induced phosphorylation of ERK as well as Mnk1 and eIF4E, suggesting
      that Mnk1/eIF4E are the downstream signaling of ERK pathway and chemotherapy
      agents activate ERK/MNK/eIF4E in a MEK-dependent manner. eIF4E overexpression
      promotes ovarian cancer cell growth without affecting migration. In addition,
      ovarian cancer cells with eIF4E overexpression are more resistant to
      chemotherapeutic agents in aspect of growth inhibition and apoptosis induction
      compared to control cells. In contrast, eIF4E depletion augments chemotherapeutic
      agents' effect in ovarian cancer cells. These demonstrate that eIF4E play roles
      in growth and chemoresistance in ovarian cancer. MEK inhibitor U0126 also
      significantly enhances chemotherapeutic agents' inhibitory effects. CONCLUSIONS:
      Our work shows that ERK/Mnk/eIF4E activation is critically involved in ovarian
      cancer chemoresistance and inhibiting ERK/Mnk/eIF4E broadly sensitizes ovarian
      cancer response to chemotherapy.

PMID- 28766097
TI  - Ranking docking poses by graph matching of protein-ligand interactions: lessons
      learned from the D3R Grand Challenge 2.
AB  - A novel docking challenge has been set by the Drug Design Data Resource (D3R) in
      order to predict the pose and affinity ranking of a set of Farnesoid X receptor
      (FXR) agonists, prior to the public release of their bound X-ray structures and
      potencies. In a first phase, 36 agonists were docked to 26 Protein Data Bank
      (PDB) structures of the FXR receptor, and next rescored using the in-house
      developed GRIM method. GRIM aligns protein-ligand interaction patterns of docked
      poses to those of available PDB templates for the target protein, and rescore
      poses by a graph matching method. In agreement with results obtained during the
      previous 2015 docking challenge, we clearly show that GRIM rescoring improves the
      overall quality of top-ranked poses by prioritizing interaction patterns already
      visited in the PDB. Importantly, this challenge enables us to refine the
      applicability domain of the method by better defining the conditions of its
      success. We notably show that rescoring apolar ligands in hydrophobic pockets
      leads to frequent GRIM failures. In the second phase, 102 FXR agonists were
      ranked by decreasing affinity according to the Gibbs free energy of the
      corresponding GRIM-selected poses, computed by the HYDE scoring function.
      Interestingly, this fast and simple rescoring scheme provided the third most
      accurate ranking method among 57 contributions. Although the obtained ranking is
      still unsuitable for hit to lead optimization, the GRIM-HYDE scoring scheme is
      accurate and fast enough to post-process virtual screening data.

PMID- 28766098
TI  - Perceived barriers and preferred components for physical activity interventions
      in African-American survivors of breast or endometrial cancer with type 2
      diabetes: the S.U.C.C.E.S.S. framework.
AB  - PURPOSE: African-American (AA) female cancer survivors share a disproportionate
      burden of diabetes compared to their white counterparts. Our objectives were to
      explore the perspectives of AA survivors with type 2 diabetes on perceived
      barriers to physical activity (PA) and preferences for a PA intervention and
      develop a framework for a PA program after cancer treatment. METHODS: Trained
      interviewers conducted semi-structured interviews with AA survivors of breast or
      endometrial cancer with diabetes (total n = 20; 16 breast, 4 endometrial).
      Thirteen open-ended questions were posed to stimulate discussions, which were
      audio recorded and transcribed verbatim. Two investigators independently reviewed
      transcriptions and extracted coded quotations to identify major themes. RESULTS:
      Median age of participants was 63 years. Nine themes were identified that focused
      on post-treatment physical symptoms (e.g., lymphedema, bone/joint pain,
      depression symptoms and self-motivation as barriers to PA, exercise routines
      tailored to physical limitations and peer partners and program leaders who
      understand their emotional health needs). The S.U.C.C.E.S.S. framework summarizes
      the survivors' preferences for an effective lifestyle intervention: Support
      efforts to maintain PA, Understand physical and depression symptoms, Collaborate
      with multi-disciplinary provider, Coordinate in-person intervention activities,
      Encourage partnerships among survivors for comorbidity risk reduction, develop
      Sustainable coping strategies for side effects of treatment, and Share local
      community resources. CONCLUSIONS: Survivors verbalized the need for a multi
      disciplinary team to assist with their psychosocial needs and physical
      limitations to achieve their PA goals, as integrated into the S.U.C.C.E.S.S.
      FRAMEWORK:  IMPLICATIONS FOR CANCER SURVIVORS: The S.U.C.C.E.S.S. framework
      reflects the perspectives of survivors with type 2 diabetes and may help to
      inform post-treatment programs.

PMID- 28766099
TI  - Efficacy of palonosetron to prevent delayed nausea and vomiting in non-Hodgkin's
      lymphoma patients undergoing repeated cycles of the CHOP regimen.
AB  - PURPOSE: Few studies have investigated the effect of palonosetron on delayed
      chemotherapy-induced nausea and vomiting in lymphoma patients receiving the CHOP
      regimen. We conducted a prospective clinical trial to assess the efficacy of
      palonosetron in patients receiving the CHOP regimen. METHODS: Complete control
      (CC: emesis-free and mild nausea) during delayed phase (24-120 h) was the primary
      endpoint. The secondary endpoint was complete response (CR: emesis-free) during
      acute (0-24 h), delayed, and overall phases (0-120 h), and CC during acute and
      overall phases. Palonosetron (0.75 mg) was administered before chemotherapy on
      day 1 of both the first and second CHOP cycles. RESULTS: The efficacy of
      palonosetron in preventing emesis was evaluated in 40 patients. Across two
      cycles, over 85% of patients achieved CR. As the primary endpoint, the proportion
      of patients achieving CC in the delayed phase increased from 70% (cycle 1) to 85%
      (cycle 2). CR rate in the delayed phase increased from 85% (cycle 1) to 95%
      (cycle 2). CONCLUSION: These results suggest that the antiemetic effects during
      the delayed phase were inferior to those in the acute phase during the first
      cycle. However, even at the same dose of palonosetron, CR and CC rates increased
      in the second cycle.

PMID- 28766100
TI  - Anticholinergic burden and health outcomes among older adults discharged from
      hospital: results from the CRIME study.
AB  - PURPOSE: The purpose of this study is to investigate whether there is an
      association between anticholinergic burden and mortality or rehospitalization in
      older adults discharged from hospital. METHODS: Prospective multicenter cohort
      study carried out with patients aged 65 and older discharged from seven acute
      care hospitals. The primary outcomes of the study were rehospitalization and
      mortality within 1 year after discharge. The study population was classified in
      three groups according to the anticholinergic exposure measured by the
      Anticholinergic Risk Scale (ARS) and Duran's list at the time of hospital
      discharge: without risk (ARS/Duran = 0), low risk (ARS/Duran = 1), and high risk
      (ARS/Duran >= 2). Predictors of hospitalizations and mortality were examined
      using regression models adjusting for important covariates. RESULTS: The mean age
      of the 921 participants was 81.2 years (SD = 7.4 years). Prevalence of exposure
      to medications with anticholinergic activity ranged from 19.6% with ARS to 32.1%
      with Duran's list. During the follow-up period, 30.4% of participants were
      hospitalized and 19.4% died. Multivariate regression analysis showed that low
      anticholinergic burden quantified according to Duran's list was significantly
      associated with all-cause mortality (OR 1.69, 95% CI 1.02-2.82). This association
      was not present after adjustment when using ARS. No statistically significant
      association was found between anticholinergic burden and hospitalizations.
      CONCLUSIONS: Taking medications with anticholinergic activity is associated with
      greater risk of mortality in older adults discharged from acute care hospitals.
      Strategies to reduce anticholinergic burden in vulnerable elders could be useful
      to improve health outcomes. Further research is required to assess the
      association between anticholinergic burden and hospitalizations in older
      patients.

PMID- 28766101
TI  - Progresses about the Interplay among Clarithromycin, Immune and Central Nervous
      Systems.

PMID- 28766103
TI  - Protocol-Driven Decision Support within e-Referral Systems to Streamline Patient
      Consultation, Triaging and Referrals from Primary Care to Specialist Clinics.
AB  - Patient referral is a protocol where the referring primary care physician refers
      the patient to a specialist for further treatment. The paper-based current
      referral process at times lead to communication and operational issues, resulting
      in either an unfulfilled referral request or an unnecessary referral request.
      Despite the availability of standardized referral protocols they are not readily
      applied because they are tedious and time-consuming, thus resulting in suboptimal
      referral requests. We present a semantic-web based Referral Knowledge Modeling
      and Execution Framework to computerize referral protocols, clinical guidelines
      and assessment tools in order to develop a computerized e-Referral system that
      offers protocol-based decision support to streamline and standardize the referral
      process. We have developed a Spinal Problem E-Referral (SPER) system that
      computerizes the Spinal Condition Consultation Protocol (SCCP) mandated by the
      Halifax Infirmary Division of Neurosurgery (Halifax, Canada) for referrals for
      spine related conditions (such as back pain). The SPER system executes the
      ontologically modeled SCCP to determine (i) patient's triaging option as per
      severity assessments stipulated by SCCP; and (b) clinical recommendations as per
      the clinical guidelines incorporated within SCCP. In operation, the SPER system
      identifies the critical cases and triages them for specialist referral, whereas
      for non-critical cases SPER system provides clinical guideline based
      recommendations to help the primary care physician effectively manage the
      patient. The SPER system has undergone a pilot usability study and was deemed to
      be easy to use by physicians with potential to improve the referral process
      within the Division of Neurosurgery at QEII Health Science Center, Halifax,
      Canada.

PMID- 28766104
TI  - Protein Engineering and Homologous Expression of Serratia marcescens Lipase for
      Efficient Synthesis of a Pharmaceutically Relevant Chiral Epoxyester.
AB  - The lipase isolated from Serratia marcescens (LipA) is a useful biocatalyst for
      kinetic resolution of a pharmaceutically relevant epoxyester, (+/-)-3-(4'
      methoxyphenyl) glycidic acid methyl ester [(+/-)-MPGM], to afford optically pure
      (-)-MPGM, a key intermediate for the synthesis of diltiazem hydrochloride. Two
      mutants, LipAL315S and LipAS271F, were identified from the combinatorial
      saturation mutation library of 14 amino acid residues lining the substrate
      binding pocket. LipAL315S, LipAS271F, and their combination LipAL315S/S271F
      showed 2.6-, 2.2-, and 4.6-fold improvements in their specific activities towards
      para-nitrophenyl butyrate (pNPB), respectively. Among these positive mutants,
      LipAS271F displayed a 3.5-fold higher specific activity towards the pharmaco
      substrate (+/-)-MPGM. Kinetic study showed that the improvement in catalytic
      efficiency of LipAS271F against (+/-)-MPGM was mainly resulted from the enhanced
      affinity between substrate and enzyme, as indicated by the decrease of K m.
      Furthermore, to address the insoluble expression issue in Escherichia coli, the
      homologous expression of LipA gene in S. marcescens was achieved by introducing
      it into an expression vector pUC18, resulting in ca. 20-fold higher lipase
      production. The significantly improved volumeric production and specific activity
      of S. marcescens lipase make it very attractive as a new-generation biocatalyst
      for more efficient and economical manufacturing of (-)-MPGM.

PMID- 28766105
TI  - The development of a novel knowledge-based weaning algorithm using pulmonary
      parameters: a simulation study.
AB  - Weaning is important for patients and clinicians who have to determine correct
      weaning time so that patients do not become addicted to the ventilator. There are
      already some predictors developed, such as the rapid shallow breathing index
      (RSBI), the pressure time index (PTI), and Jabour weaning index. Many important
      dimensions of weaning are sometimes ignored by these predictors. This is an
      attempt to develop a knowledge-based weaning process via fuzzy logic that
      eliminates the disadvantages of the present predictors. Sixteen vital parameters
      listed in published literature have been used to determine the weaning decisions
      in the developed system. Since there are considered to be too many individual
      parameters in it, related parameters were grouped together to determine acid-base
      balance, adequate oxygenation, adequate pulmonary function, hemodynamic
      stability, and the psychological status of the patients. To test the performance
      of the developed algorithm, 20 clinical scenarios were generated using Monte
      Carlo simulations and the Gaussian distribution method. The developed knowledge
      based algorithm and RSBI predictor were applied to the generated scenarios.
      Finally, a clinician evaluated each clinical scenario independently. The
      Student's t test was used to show the statistical differences between the
      developed weaning algorithm, RSBI, and the clinician's evaluation. According to
      the results obtained, there were no statistical differences between the proposed
      methods and the clinician evaluations.

PMID- 28766102
TI  - A New Chapter for Mesenchymal Stem Cells: Decellularized Extracellular Matrices.
AB  - From orthopedic to neurological disorders, stem cells are used as platforms to
      understand disease mechanisms and considered as novel and promising treatment
      options, especially when the valid therapeutic approaches are unavailable or
      ineffective. There are different stem cell types in the literature, however the
      spindle-shaped, colony forming and multilineage-differentiating cells, also known
      as mesenchymal stem cells (MSC) are very popular, as MSC can be isolated from
      different tissues with minimal ethical concerns and without tumor formations,
      which make them easily accessible and widely used in vitro and in vivo studies.
      In the literature, MSC have been shown to have therapeutic effects and
      orchestrate the healing process via their mobilization, migration,
      differentiation capacities, immunomodulation properties and/or secretion of
      bioactive factors. Nowadays, MSC derived extracellular matrices (ECM), which are
      part of the secreted/produced bioactive molecules from MSC; draw attention of
      researchers due to their key roles in cell biology. Several groups have isolated
      ECM from in vitro cultured MSC using different methods of decellularization
      techniques for tissue-engineering approaches. According to current knowledge,
      decellularized ECM (dECM) influence growth, adhesion, differentiation, migration,
      apoptosis, proliferation, and phenotype of cells, covering almost all cellular
      events. In this comprehensive review we focused on MSC and the isolation methods
      and effects of MSC derived dECM (MSC-dECM).

PMID- 28766106
TI  - A piecewise function of resistivity of liver: determining parameters with finite
      element analysis of radiofrequency ablation.
AB  - Radiofrequency ablation (RFA) is a widely used thermal treatment for liver
      tumors. Knowledge about the resistivity of liver is a prerequisite for the
      predictability of producible thermo-necrosis with RFA. Most research to date has
      focused on performing specific experiments to determine the resistivity of a
      given liver. This work aims to determine the resistivity from the time course of
      impedance obtained in RFA. We assume that the liver resistivity obeys a piecewise
      function of temperature. We determine in this work the means and standard
      derivations of parameters in the resistivity function with finite element
      analysis of ex vivo bipolar RFA. We experimentally found the temperature at the
      electrode equal to 125.2  degrees C. This finding validates a parameter in the
      function relating to the temperature at which the resistivity starts to rise
      exponentially. We conclude that it is feasible and reliable to characterize the
      resistivity function of liver in using the time course of impedance from RFA.
      This work opens a pathway for the automatic determination of the patient specific
      resistivity of in vivo liver.

PMID- 28766107
TI  - Examining of Thallium in Cigarette Smokers.
AB  - Smoking is one of the sources of thallium which is considered as a toxic heavy
      metal. The aim of this study was to determine urinary thallium levels and related
      variables in smokers, compared to a control group. The study was conducted on 56
      participants who had smoked continuously during the year before they were
      referred to Kashan Smoking Cessation Clinic. Fifty-three nonsmokers who were
      family members or friends of the smokers were selected as the control group.
      Urinary thallium was measured in both groups (n = 109) using atomic absorption
      spectrophotometry. The mean value (with SD) for urinary thallium in the smokers
      (10.16 +/- 1.82 MUg/L) was significantly higher than in the control group (2.39
      +/- 0.63 MUg/L). There was a significant relationship between smoking duration
      and urinary thallium levels (P = 0.003). In a subgroup of smokers who was
      addicted to opium and opium residues (n = 9), the mean level of thallium (37.5 +/
      13.09 MUg/L) was significantly higher than in the other smokers (4.93 +/- 4.45;
      P = 0.001). Multiple regression analysis showed opioid abuse, insomnia, and
      chronic obstructive pulmonary disease (COPD), together were strong predictors of
      urinary thallium levels in smokers. There was no significant difference in
      thallium level in hookah smokers (P = 0.299) or in those with COPD compared to
      other smokers (P = 0.375). Urinary thallium levels of smokers with clinical signs
      of depression, sleep disorders, memory loss, and sweating were higher than those
      of smokers without these signs. Since thallium, as other toxic metals is
      accumulated in the body, and cigarette smoking also involves carcinogenic
      exposures and health hazards for passively exposed people, the need for cigarette
      control policies is emphasized.

PMID- 28766108
TI  - A Pharmacoepidemiology Database System for Monitoring Risk Due to the Use of
      Medicines by New Zealand Primary Care Patients.
AB  - INTRODUCTION: The use of large record-linked healthcare databases for drug safety
      research and surveillance is now accepted practice. New Zealand's standardized
      national healthcare datasets provide the potential to automate the conduct of
      pharmacoepidemiological studies to provide rapid validation of medicine safety
      signals. OBJECTIVES: Our objectives were to describe the methodology undertaken
      by a semi-automated computer system developed to rapidly assess risk due to drug
      exposure in New Zealand's population of primary care patients and to compare
      results from three studies with previously published findings. METHODS: Data from
      three national databases were linked at the patient level in the automated
      studies. A retrospective nested case-control design was used to evaluate risk for
      upper gastrointestinal bleeding (UGIB), acute kidney failure (AKF), and serious
      arrhythmia associated with individual medicines, therapeutic classes of
      medicines, and concurrent use of medicines from multiple therapeutic classes.
      RESULTS: The patient cohort available for each study included 5,194,256 patients
      registered between 2007 and 2014, with a total of 34,630,673 patient-years at
      risk. An increased risk for UGIB was associated with non-steroidal anti
      inflammatory drugs (NSAIDs) (adjusted odds ratio [AOR] 4.16, 95% confidence
      interval [CI] 3.90-4.43, p < 0.001) and selective serotonin reuptake inhibitors
      (AOR 1.39, 95% CI 1.20-1.62, p < 0.001); an increased risk for AKF was associated
      with NSAIDs (AOR 1.78, 95% CI 1.73-1.83, p < 0.001) and proton pump inhibitors
      (AOR 1.78, 95% CI 1.72-1.83, p < 0.001); and an increased risk for serious
      arrhythmia was associated with fluoroquinolones (AOR 1.38, 95% CI 1.26-151, p <
      0.001) and penicillins (AOR 1.69, 95% CI 1.61-1.77, p < 0.001). CONCLUSIONS:
      Automated case-control studies using New Zealand's healthcare datasets can
      replicate associations of risk with drug exposure consistent with previous
      findings. Their speed of conduct enables systematic monitoring of risk for
      adverse events associated with a wide range of medicines.

PMID- 28766109
TI  - Treatment of Medication-Related Osteonecrosis of the Jaw and its Impact on a
      Patient's Quality of Life: A Single-Center, 10-Year Experience from Southern
      Italy.
AB  - INTRODUCTION: No official guidelines are available for the management of
      medication-related osteonecrosis of the jaw (MR-ONJ). The additional benefit of
      surgery after pharmacological treatment is debated by both clinicians and
      patients. OBJECTIVE: The aim of this study was to evaluate the changes in
      patients' MR-ONJ-related quality of life (QoL) after pharmacological treatment
      with or without surgery in a large cohort affected by MR-ONJ. METHODS: Anonymized
      data on patients diagnosed with MR-ONJ were extracted from the database of the
      Osteonecrosis of the Jaw Treatment Center (University of Messina, Italy) in the
      years 2005-2015. QoL was evaluated at the moment of MR-ONJ diagnoses (T0), after
      pharmacological treatment with or without surgery (T1 and T2, respectively),
      based on scores from the European Organisation for Research and Treatment of
      Cancer (EORTC) QOL Module for Head and Neck Cancer (global oral health status
      [GOHS]) and a visual analog scale (VAS), stratified by indication for use.
      RESULTS: Among 100 patients, 36% were affected by osteoporosis (OSTEO group) and
      64% were affected by cancer (ONC group). Considering T0, QoL scores were higher
      in the OSTEO group then in the ONC group. At T1, GOHS and VAS increased in both
      groups (OSTEO group: +9.9% and +39.9%; ONC group: +35.4 and +97.2%,
      respectively). Pharmacological treatment was effective in reducing pain (OSTEO
      group: -22.0%; ONC group: -44.8%), and social contact troubles (OSTEO group: 
      40.3%; ONC group: -26.7%). At T2, GOHS and VAS further increased. Scores related
      to 'pain' and the troubles related to the 'social dimension' also decreased
      (OSTEO group: -91.3% and -72.0%; ONC group: 50.8% and -16.4%, respectively).
      CONCLUSIONS: MR-ONJ-related QoL increased after pharmacological treatment and,
      more notably, after surgery, which may offer benefits to selected patients. QoL
      data may help clinicians in promoting tailored management of MR-ONJ.

PMID- 28766110
TI  - Synchronous Polymorphous Adenocarcinoma and Canalicular Adenoma on the Upper Lip:
      An Unusual Presentation and Immunohistochemical Analysis.
AB  - Multiple salivary gland tumors (MSGTs) are most common in the major than minor
      salivary glands. The most MSGTs are synchronous, either benign or malignant. A 61
      year-old woman was referred presenting nine submucosal nodules, firm to
      fluctuant, being five nodules on the right side and four nodules on the left side
      of the upper lip. An incisional biopsy was performed. Hematoxylin and eosin
      staining was performed in 5-um sections for histopathologic analysis.
      Immunohistochemical reactions were carried out in 3-um sections in accordance
      with manufacturer's instructions. The histopathological analysis showed focal
      area containing low-grade polymorphous adenocarcinoma (PAC) and multiple
      canalicular adenomas (CAs). Immunohistochemical analysis for each lesion was
      carefully investigated. Here, we present an unusual case of synchronous PAC and
      multiple CAs of the minor salivary glands, affecting the upper lip, which appears
      to be the first case showing PAC and CA.

PMID- 28766111
TI  - Effects of the nitrogen doping configuration and site on the thermal conductivity
      of defective armchair graphene nanoribbons.
AB  - The influence of the nitrogen (N) doping configuration on the thermal
      conductivity (TC) of armchair graphene nanoribbons (AGNRs) of size 15.7 nm * 7.26
      nm was investigated using classical molecular dynamics (MD) simulations with the
      optimized Tersoff potential at room temperature. The effect of changing the N
      doping site in defects on the TC of AGNRs was also investigated in detail. The
      variations with N concentration of the TCs of AGNRs presenting graphitic N
      (quarternary N), pyridinic N, and pyrrolic N doping configurations were studied.
      Results of MD simulations showed that, among these three doping configurations,
      pyridinic N was associated with the highest TC, and pyrrolic N with the lowest
      TC. The highest TC values were obtained when the N dopant atoms were located at
      the edges and at defects in the AGNR. The presence of both pyrrolic N and Stone
      Wales type 1 (SW-1) defects led to a higher TC than the presence of both pyrrolic
      N and SW-2 defects. Phonon-defect scattering was found to be influenced by
      changes in C-C bond orientation. SW-1 defects were found to exert a greater
      influence on the TC than graphitic N doping. Furthermore, the influence on the TC
      of the N-doping site location in SW-1 defects was examined. Doping the central
      sites of SW-1 defects was found to yield higher TC values than doping the edge
      sites of defects. Graphitic-N doping of the more central sites in a SW-1 defect
      led to a higher TC than the random graphitic-N doping of sites in a SW-1 defect.

PMID- 28766112
TI  - Oleanolic acid and ursolic acid as potential inhibitors of human salivary alpha
      amylase: insights from in vitro assays and in silico simulations.
AB  - It is known that inhibiting alpha-amylase, an important enzyme in digestion of
      starch and glycogen, is a useful strategy for treating disorders in carbohydrate
      uptake. Two natural components distributed in many fruits and plants, oleanolic
      acid and ursolic acid, are endowed with important pharmacological activities and
      wide therapeutic possibilities. Until now, only a tiny fraction of their
      applications have been identified and exploited. Our in vitro inhibition studies
      demonstrated that oleanolic acid and ursolic acid non-competitively inhibit the
      activity and function of human salivary alpha-amylase. The molecular simulations
      revealed that oleanolic acid and ursolic acid interact with amino acid residues
      within the binding pocket of human salivary alpha-amylase, among which the side
      chain of Arg195 and Asp 197 was supposed to be important in imparting the
      inhibitory activity of triterpenoids. The present work will provide meaningful
      information for future development of functional drugs for the treatment of
      disorders in carbohydrate metabolism. Graphical abstract This work is valuable
      for providing a deeper insight into the interaction mechanism of oleanolic acid
      and ursolic acid with alpha-amylase.

PMID- 28766113
TI  - Increasing Inequality in Parent Incomes and Children's Schooling.
AB  - Income inequality and the achievement test score gap between high- and low-income
      children increased dramatically in the United States beginning in the 1970s. This
      article investigates the demographic (family income, mother's education, family
      size, two-parent family structure, and age of mother at birth) underpinnings of
      the growing income-based gap in schooling using data from the Panel Study of
      Income Dynamics. Across 31 cohorts, we find that increases in the income gap
      between high- and low-income children account for approximately three-quarters of
      the increasing gap in completed schooling, one-half of the gap in college
      attendance, and one-fifth of the gap in college graduation. We find no consistent
      evidence of increases in the estimated associations between parental income and
      children's completed schooling. Increasing gaps in the two-parent family
      structures of high- and low-income families accounted for relatively little of
      the schooling gap because our estimates of the (regression-adjusted) associations
      between family structure and schooling were surprisingly small for much of our
      accounting period. On the other hand, increasing gaps in mother's age at the time
      of birth accounts for a substantial portion of the increasing schooling gap:
      mother's age is consistently predictive of children's completed schooling, and
      the maternal age gap for children born into low- and high-income families
      increased considerably over the period.

PMID- 28766114
TI  - Rapid Characterization of Constituents in Tribulus terrestris from Different
      Habitats by UHPLC/Q-TOF MS.
AB  - A strategy for rapid identification of the chemical constituents from crude
      extracts of Tribulus terrestris was proposed using an informatics platform for
      the UHPLC/Q-TOF MSE data analyses. This strategy mainly utilizes neutral losses,
      characteristic fragments, and in-house library to rapidly identify the structure
      of the compounds. With this strategy, rapid characterization of the chemical
      components of T. terrestris from Beijing, China was successfully achieved. A
      total of 82 steroidal saponins and nine flavonoids were identified or tentatively
      identified from T. terrestris. Among them, 15 new components were deduced based
      on retention times and characteristic MS fragmentation patterns. Furthermore, the
      chemical components of T. terrestris, including the other two samples from
      Xinjiang Uygur Autonomous region, China, and Rome, Italy, were also identified
      with this strategy. Altogether, 141 chemical components were identified from
      these three samples, of which 39 components were identified or tentatively
      identified as new compounds, including 35 groups of isomers. It demonstrated that
      this strategy provided an efficient protocol for the rapid identification of
      chemical constituents in complex samples such as traditional Chinese medicines
      (TCMs) by UHPLC/Q-TOF MSE with informatics platform. Graphical Abstract ?.

PMID- 28766115
TI  - Is There a Role for Preoperative 5 Alpha Reductase Inhibitors in Reducing
      Prostate Vascularity and Blood Loss?
AB  - Benign prostatic hyperplasia (BPH) and the related medical problems are a major
      burden as health care costs and as a cause of patient morbidity. The introduction
      of medical therapy largely offered an alternative to surgical therapy, and these
      medications have been linked with multiple positive BPH-related outcomes. With
      ubiquitous use, however, a variety of adverse side effects and unsupported claims
      to these medications have been reported both in scientific literature and popular
      press. The use of 5 alpha reductase inhibitors (5ARIs) to reduce recurrent
      bleeding due to BPH is a reasonable option for men with recurrent trips to the
      physician or hospital. After a largely anecdotal report of their use in the
      preoperative period to reduce bleeding during BPH surgery, there was interest in
      the use of 5ARIs for this indication considering the effusive bleeding that can
      occur during BPH-related surgery, a dreaded and not uncommon complication. While
      the pathophysiology for the use of 5ARI to reduce BPH-related bleeding is sound,
      the actual clinical outcomes still require scrutiny to determine if the efficacy
      is both scientifically valid and clinically significant. This report will review
      the current literature on this topic and make attempts to determine if the use of
      a 5ARI before BPH-related surgery should be encouraged.

PMID- 28766116
TI  - Sardine oil loaded vanillic acid grafted chitosan microparticles, a new
      functional food ingredient: attenuates myocardial oxidative stress and apoptosis
      in cardiomyoblast cell lines (H9c2).
AB  - Fish oil has been widely recognized as an excellent dietary source of
      polyunsaturated n-3 fatty acids such as EPA and DHA. However, it can undergo
      oxidation easily resulting in the formation of toxic off flavor compounds such as
      hydroperoxides. These compounds adversely affect the nutritional quality and may
      induce several stress reactions in body. To solve this problem, a new antioxidant
      bio-material, vanillic acid-grafted chitosan (Va-g-Ch), was synthesized and used
      as a wall material for microencapsulation of fish oil. The sardine oil loaded Va
      g-Ch microparticles could be a potential functional food ingredient considering
      the numerous health benefits of fish oil, chitosan, and vanillic acid. The
      current study aimed to investigate the possible protective effect of sardine oil
      loaded Va-g-Ch microparticles against doxorubicin-induced cardiotoxicity and the
      underlying mechanisms. In vitro cytotoxicity evaluation was conducted using H9c2
      cardiomyocytes. MTT assay revealed that effective cytoprotective effect was
      induced by a sample concentration of 12.5 MUg/mL. Results of apoptosis by double
      fluorescent staining with acridine orange/ethidium bromide and caspase-3
      evaluation by ELISA substantiated the above findings. Further, flow cytometric
      determination of membrane potential, relative expression of NF-kappaB by PCR, and
      ROS determination using DCFH-DA also confirmed the protective effect of
      encapsulated sardine oil against doxorubicin-induced cardiotoxicity. NF-kappaB
      expression was down-regulated nearly by 50% on cells treated with encapsulated
      sardine oil. Altogether, the results revealed that sardine oil-loaded Va-g-Ch
      microparticles demonstrated potential cell protection against doxorubicin-induced
      oxidative stress.

PMID- 28766117
TI  - The effect of bicephalic stimulation of the dorsolateral prefrontal cortex on the
      attentional bias for threat: A transcranial direct current stimulation study.
AB  - Previous stimulation studies demonstrated that the dorsolateral prefrontal cortex
      (DLPFC) is involved in threat processing. According to a model of emotional
      processing, an unbalance between the two DLPFCs, with a hyperactivation of right
      frontal areas, is involved in the processing of negative emotions and genesis of
      anxiety. In the present study, we investigated the role of the right and left
      DLPFC in threat processing in healthy women who also completed the State-Trait
      Anxiety Inventory (STAI). We simultaneously modulated the activity of the right
      and left dorsolateral prefrontal cortex by applying bicephalic transcranial
      direct current stimulation (tDCS) before participants completed a modified
      version of the classic Posner task using threatening and nonthreatening stimuli
      as spatial cues. Anodal stimulation on the right DLPFC with a simultaneous
      cathodal stimulation over the left side induced a disengagement bias in
      individuals with low STAI scores and a facilitation bias in individuals with high
      STAI scores. Anodal stimulation on the left DLPFC with the simultaneous cathodal
      stimulation over the right side did not affect threat processing. The findings of
      the present study provided specific support to the hypothesis that unbalanced
      activation between left and right hemispheres with enhanced activation of the
      right DLPFC is critical in early top-down threat processing in healthy
      individuals.

PMID- 28766118
TI  - Dental and craniofacial findings in 91 individuals with agenesis of permanent
      maxillary canines.
AB  - AIM: Agenesis of maxillary permanent canines is a rare form of agenesis
      (prevalence 0.07-0.13%). The aetiology is still unknown. The purpose was to focus
      on dentitions and craniofacial profiles in individuals with maxillary canine
      agenesis. METHOD: From 91 individuals (10-18 years of age) 91 Orthopantomograms
      and 77 profile radiographs were divided accordingly: Group I: agenesis of 1 or 2
      maxillary canines. Group II: several ageneses including the maxillary canines.
      Dentition analysis included crown/root shape, invaginations, eruption
      disturbances and resorption patterns. Cephalometric angular measurements and
      mutual comparisons between the groups were performed. Agenesis pattern in Group
      II was compared to agenesis pattern in a population of children and young adults
      not characterized by maxillary canine agenesis. Cephalometric values from both
      groups were compared to normal values from individuals without agenesis. Findings
      were statistically evaluated. RESULTS: Dentition: Group I: only the missing
      maxillary canines were deemed to be in an abnormal dental deviation. Group II:
      abnormal dental development regarding morphology, resorption of primary teeth and
      also agenesis of the first maxillary premolar. Comparison of the groups showed a
      difference in the pattern of malformation. Profile: Group I: anterior inclination
      of the maxilla and increased cranial base angle were significant findings. Group
      II: diminished incisor slope in the maxilla and enlarged cranial base angle were
      significant findings. A comparison showed a difference in maxillary inclinations
      of the teeth. CONCLUSION: Group I dentitions are normally developed with only
      minor dental malformations. Group II dentitions had several dental malformations
      and often agenesis of the first maxillary premolar. Significant findings: first
      maxillary premolar agenesis in Group II and enlarged cranial base angle in both
      groups.

PMID- 28766119
TI  - Professor Yves Goffin, M.D., Ph.D., the founder of the European Homograft Bank
      (EHB) past away.

PMID- 28766120
TI  - [Treatment of indolent cutaneous B-cell lymphoma].
AB  - Primary cutaneous B-cell lymphomas are rarely encountered and represent 25% of
      all cutaneous lymphomas. Follicular B-cell lymphoma and marginal zone lymphoma
      belong to indolent subtypes which as a rule have no systemic dissemination and,
      thus, a mostly unchanged life expectancy. Therefore, skin-directed treatment
      options such as excision or radiotherapy are usually sufficient to control the
      disease. In contrast, cutaneous diffuse large B-cell lymphoma and EBV-associated
      B-cell lymphomas of the skin belong to more aggressive entities which demand a
      systemic first-line upfront therapy with R-CHOP. Nevertheless, mortality is still
      high and comparable to that of systemic/nodal large B-cell lymphomas so that the
      identification of pathogenetic driver mutations or novel therapeutic targets may
      pave the way to better target-oriented therapies.

PMID- 28766121
TI  - Estimation of tile drainage contribution to streamflow and nutrient loads at the
      watershed scale based on continuously monitored data.
AB  - Nitrogen losses from artificially drained watersheds degrade water quality at
      local and regional scales. In this study, we used an end-member mixing analysis
      (EMMA) together with high temporal resolution water quality and streamflow data
      collected in the 122 km2 Otter Creek watershed located in northeast Iowa. We
      estimated the contribution of three end-members (groundwater, tile drainage, and
      quick flow) to streamflow and nitrogen loads and tested several combinations of
      possible nitrate concentrations for the end-members. Results indicated that
      subsurface tile drainage is responsible for at least 50% of the watershed
      nitrogen load between April 15 and November 1, 2015. Tiles delivered up to 80% of
      the stream N load while providing only 15-43% of the streamflow, whereas quick
      flows only marginally contributed to N loading. Data collected offer guidance
      about areas of the watershed that should be targeted for nitrogen export
      mitigation strategies.

PMID- 28766122
TI  - Study of macro and microelements in fish from the Cienfuegos Bay. Relationship
      with its content in sediments.
AB  - Thirteen microelements (Al, As, Cd, Co, Cr, Cu, Fe, Li, Mn, Ni, Ti, V, and Zn)
      and four macroelements (Ca, K, Mg, and Na) were determined in the edible muscle
      tissue of fish in Cienfuegos Bay. Eight species, Albula vulpes, Diapterus
      rhombeus, Gerres cinereus, Haemulon carbonarium, Haemulon sciurus, Micropogonias
      furnieri, Kyphosus sectatrix, and Lutjanus cyanopterus were studied. The total
      concentrations and extracted concentrations using HCl were also determined in
      sediments. The quality of the analysis was guaranteed by validating the used
      analytical methods with certified reference materials of fish and sediments. The
      high content of macroelements confirmed the importance of fish as a valuable
      source of food for the local population. New information is provided on
      bioaccumulation of toxic elements As, Cd, Cu, Zn, and Cr in fish of the bay, with
      concentrations that overcame the local or international maximum allowable levels
      for human consumption in most samples analyzed. A high correlation between the
      content of toxic elements As, Cd, Zn, and macroelement K in fish and its
      concentration extracted from sediments using the HCl extraction method was
      observed.

PMID- 28766123
TI  - Screening the ToxCast phase II libraries for alterations in network function
      using cortical neurons grown on multi-well microelectrode array (mwMEA) plates.
AB  - Methods are needed for rapid screening of environmental compounds for
      neurotoxicity, particularly ones that assess function. To demonstrate the utility
      of microelectrode array (MEA)-based approaches as a rapid neurotoxicity screening
      tool, 1055 chemicals from EPA's phase II ToxCast library were evaluated for
      effects on neural function and cell health. Primary cortical networks were grown
      on multi-well microelectrode array (mwMEA) plates. On day in vitro 13, baseline
      activity (40 min) was recorded prior to exposure to each compound (40 uM).
      Changes in spontaneous network activity [mean firing rate (MFR)] and cell
      viability (lactate dehydrogenase and CellTiter Blue) were assessed within the
      same well following compound exposure. Following exposure, 326 compounds altered
      (increased or decreased) normalized MFR beyond hit thresholds based on 2* the
      median absolute deviation of DMSO-treated wells. Pharmaceuticals, pesticides,
      fungicides, chemical intermediates, and herbicides accounted for 86% of the hits.
      Further, changes in MFR occurred in the absence of cytotoxicity, as only eight
      compounds decreased cell viability. ToxPrint chemotype analysis identified
      several structural domains (e.g., biphenyls and alkyl phenols) significantly
      enriched with MEA actives relative to the total test set. The top 5 enriched
      ToxPrint chemotypes were represented in 26% of the MEA hits, whereas the top 11
      ToxPrints were represented in 34% of MEA hits. These results demonstrate that
      large-scale functional screening using neural networks on MEAs can fill a
      critical gap in assessment of neurotoxicity potential in ToxCast assay results.
      Further, a data-mining approach identified ToxPrint chemotypes enriched in the
      MEA-hit subset, which define initial structure-activity relationship inferences,
      establish potential mechanistic associations to other ToxCast assay endpoints,
      and provide working hypotheses for future studies.

PMID- 28766124
TI  - Human lung injury following exposure to humic substances and humic-like
      substances.
AB  - Among the myriad particles the human respiratory tract is exposed to, a
      significant number are distinctive in that they include humic substances (HS) and
      humic-like substances (HULIS) as organic components. HS are heterogeneous,
      amorphous, organic materials which are ubiquitous occurring in all terrestrial
      and aqueous environments. HULIS are a complex class of organic, macromolecular
      compounds initially extracted from atmospheric aerosol particles which share some
      features with HS including an aromatic, polyacidic nature. As a result of having
      a variety of oxygen-containing functional groups, both HS and HULIS complex metal
      cations, especially iron. Following particle uptake by cells resident in the
      lung, host iron will be sequestered by HS- and HULIS-containing particles
      initiating pathways of inflammation and subsequent fibrosis. It is proposed that
      (1) human exposures to HS and HULIS of respirable size (<10 um diameter) are
      associated with inflammatory and fibrotic lung disease and (2) following
      retention of particles which include HS and HULIS, the mechanism of cell and
      tissue injury involves complexation of host iron. Human inflammatory and fibrotic
      lung injuries following HS and HULIS exposures may include coal workers'
      pneumoconiosis, sarcoidosis, and idiopathic pulmonary fibrosis as well as
      diseases associated with cigarette smoking and exposures to emission and ambient
      air pollution particles.

PMID- 28766126
TI  - Partnering with Psychiatry to Close the Education Gap: An Approach to the
      Addiction Epidemic.
AB  - Addiction has reached epidemic proportions in the U.S., yet the workforce
      prepared to care for this population is woefully inadequate. Of the 23 million
      Americans suffering from addiction, only 11% receive treatment, creating a
      substantial treatment gap. There have been calls to improve addiction education
      at all levels of training in order to prepare medical providers with the skills
      to identify patients with substance use, briefly treat if indicated, and/or refer
      more complex cases to specialty care. These calls have been put forth to address
      the education gap, wherein physicians in training are exposed to numerous
      patients who are suffering from addiction but have few curricular hours dedicated
      to the identification and management of this population. We propose that
      strategic partnerships between psychiatry and internal medicine can address the
      education gap that exists with regard to addiction, ultimately addressing the
      treatment gap which is plaguing this country.

PMID- 28766125
TI  - Medical School Factors Associated with Changes in Implicit and Explicit Bias
      Against Gay and Lesbian People among 3492 Graduating Medical Students.
AB  - BACKGROUND: Implicit and explicit bias among providers can influence the quality
      of healthcare. Efforts to address sexual orientation bias in new physicians are
      hampered by a lack of knowledge of school factors that influence bias among
      students. OBJECTIVE: To determine whether medical school curriculum, role
      modeling, diversity climate, and contact with sexual minorities predict bias
      among graduating students against gay and lesbian people. DESIGN: Prospective
      cohort study. PARTICIPANTS: A sample of 4732 first-year medical students was
      recruited from a stratified random sample of 49 US medical schools in the fall of
      2010 (81% response; 55% of eligible), of which 94.5% (4473) identified as
      heterosexual. Seventy-eight percent of baseline respondents (3492) completed a
      follow-up survey in their final semester (spring 2014). MAIN MEASURES: Medical
      school predictors included formal curriculum, role modeling, diversity climate,
      and contact with sexual minorities. Outcomes were year 4 implicit and explicit
      bias against gay men and lesbian women, adjusted for bias at year 1. KEY RESULTS:
      In multivariate models, lower explicit bias against gay men and lesbian women was
      associated with more favorable contact with LGBT faculty, residents, students,
      and patients, and perceived skill and preparedness for providing care to LGBT
      patients. Greater explicit bias against lesbian women was associated with
      discrimination reported by sexual minority students (b = 1.43 [0.16, 2.71]; p =
      0.03). Lower implicit sexual orientation bias was associated with more frequent
      contact with LGBT faculty, residents, students, and patients (b = -0.04 [-0.07, 
      0.01); p = 0.008). Greater implicit bias was associated with more faculty role
      modeling of discriminatory behavior (b = 0.34 [0.11, 0.57); p = 0.004).
      CONCLUSIONS: Medical schools may reduce bias against sexual minority patients by
      reducing negative role modeling, improving the diversity climate, and improving
      student preparedness to care for this population.

PMID- 28766127
TI  - Metabolic profiling of gestational diabetes in obese women during pregnancy.
AB  - AIMS/HYPOTHESIS: Antenatal obesity and associated gestational diabetes (GDM) are
      increasing worldwide. While pre-existing insulin resistance is implicated in GDM
      in obese women, the responsible metabolic pathways remain poorly described. Our
      aim was to compare metabolic profiles in blood of obese pregnant women with and
      without GDM 10 weeks prior to and at the time of diagnosis by OGTT. METHODS: We
      investigated 646 women, of whom 198 developed GDM, in this prospective cohort
      study, a secondary analysis of UK Pregnancies Better Eating and Activity Trial
      (UPBEAT), a multicentre randomised controlled trial of a complex lifestyle
      intervention in obese pregnant women. Multivariate regression analyses adjusted
      for multiple testing, and accounting for appropriate confounders including study
      intervention, were performed to compare obese women with GDM with obese non-GDM
      women. We measured 163 analytes in serum, plasma or whole blood, including 147
      from a targeted NMR metabolome, at time point 1 (mean gestational age 17 weeks 0
      days) and time point 2 (mean gestational age 27 weeks 5 days, at time of OGTT)
      and compared them between groups. RESULTS: Multiple significant differences were
      observed in women who developed GDM compared with women without GDM (false
      discovery rate corrected p values <0.05). Most were evident prior to diagnosis.
      Women with GDM demonstrated raised lipids and lipoprotein constituents in VLDL
      subclasses, greater triacylglycerol enrichment across lipoprotein particles,
      higher branched-chain and aromatic amino acids and different fatty acid, ketone
      body, adipokine, liver and inflammatory marker profiles compared with those
      without GDM. CONCLUSIONS/INTERPRETATION: Among obese pregnant women, differences
      in metabolic profile, including exaggerated dyslipidaemia, are evident at least
      10 weeks prior to a diagnosis of GDM in the late second trimester.

PMID- 28766128
TI  - The influence of Generalized Anxiety Disorder on Executive Functions in children
      with ADHD.
AB  - The present study was aimed at verifying whether the presence of generalized
      anxiety disorder (GAD) affects executive functions in children with attention
      deficit hyperactivity disorder (ADHD). Two groups of children with ADHD were
      selected for the study according to the presence or absence of GAD. The first
      group of 28 children with ADHD with GAD (mean age: 9 +/- 1.2; males/females:
      24/4) was matched for gender, age, IQ, psychiatric comorbidity with a second
      group of 29 children with ADHD without GAD (mean age: 8.8 +/- 0.7; males/females:
      26/3). The two groups with ADHD were compared to 28 typically developing children
      (mean age: 8.3 +/- 1.3; males/females: 23/5) on different measures involving
      processes especially important in inhibitory control such as rule maintenance,
      stimulus detection, action selection and action execution. Our results indicated
      that, differently from children with ADHD with GAD, only the group with ADHD
      without GAD showed a deficit in inhibitory control. Comorbid subgroups should be
      differentiated, especially, to develop specific and efficient therapeutic
      interventions in ADHD.

PMID- 28766130
TI  - Detection of multicentric and contralateral breast cancers on MRI based on
      primary cancer biomarker status: will this change surgical or medical management?
AB  - PURPOSE: The utilization of staging preoperative breast MRI in biopsy-proven
      cancer patients varies based on institution and individual clinicians. It is
      unclear whether primary breast cancer subtype influences a clinician's decision
      to obtain a preoperative breast MRI based on likelihood of multicentric or
      contralateral disease, which may change surgical or medical management. Our
      purpose was to compare the four main breast cancer subtypes in our patient
      population (i.e., luminal A, luminal B, HER2 enriched and triple-negative) who
      underwent pretreatment staging MRIs to determine whether certain breast cancer
      subtypes are more likely to have multicentric or contralateral disease. METHODS:
      We retrospectively reviewed 435 patients with biopsy-proven invasive breast
      cancer who had staging MRI. RESULTS: Of these patients, 14 had biopsy-proven
      multicentric disease (3.2% of total) and 15 had biopsy-proven contralateral
      second tumor sites (3.4% of total). There was no statistically significant
      difference between primary tumor subtype and likelihood of multicentric or
      contralateral disease (p = 0.3065). CONCLUSION: Pretreatment staging MRI can
      detect multicentric and/or contralateral additional tumor sites, which ultimately
      changes staging, treatment options, and outcomes for patients with biopsy-proven
      breast cancer. There is no correlation between primary breast cancer subtype and
      likelihood of multicentric or contralateral disease.

PMID- 28766129
TI  - Use and safety of antiepileptic drugs in psychiatric inpatients-data from the
      AMSP study.
AB  - The psychiatric utilization patterns and risks of antiepileptic drugs (AEDs) were
      assessed by using data from the drug safety programme Arzneimittelsicherheit in
      der Psychiatrie over the time period 1993-2013. In a total of 432,215 patients,
      the main indications for AED use were acute mania, schizoaffective disorder, and
      schizophrenic and organic psychoses. Valproic acid (VPA) was the most common
      substance across all of those groups, reaching administration rates of up to 50%
      since 2005, at which time carbamazepine (CBZ) administration consistently dropped
      below a rate of 10%. Lamotrigine (LTG) and pregabalin (PGB) increased in
      relevance after 2005 and 2010, respectively (with administration rates of up to
      9%), whereas oxcarbazepine (OXC) was least prevalent (<3%). The mean rates of
      severe adverse drug reactions (ADRs) ranged from 6 cases per 1000 patients
      treated (VPA) to 19/1000 (OXC) and were significantly lower with treatment with
      VPA compared to OXC and CBZ. Hyponatremia was the leading ADR during treatment
      with OXC; severe allergic skin reactions were most often observed during
      treatment with CBZ and LTG, and severe oedema was most common during treatment
      with PGB. Severe hyponatremia induced by OXC was observed significantly more
      often in female patients than in male patients.

PMID- 28766131
TI  - Outcome following sentinel lymph node biopsy-guided decisions in breast cancer
      patients with conversion from positive to negative axillary lymph nodes after
      neoadjuvant chemotherapy.
AB  - PURPOSE: Many breast cancer patients with positive axillary lymph nodes achieve
      complete node remission after neoadjuvant chemotherapy. The usefulness of
      sentinel lymph node biopsy in this situation is uncertain. This study evaluated
      the outcomes of sentinel biopsy-guided decisions in patients who had conversion
      of axillary nodes from clinically positive to negative following neoadjuvant
      chemotherapy. METHODS: We reviewed the records of 1247 patients from five
      hospitals in Korea who had breast cancer with clinically axillary lymph node
      positive status and negative conversion after neoadjuvant chemotherapy, between
      2005 and 2012. Patients who underwent axillary operations with sentinel biopsy
      guided decisions (Group A) were compared with patients who underwent complete
      axillary lymph node dissection without sentinel lymph node biopsy (Group B).
      Axillary node recurrence and distant recurrence-free survival were compared.
      RESULTS: There were 428 cases in Group A and 819 in Group B. Kaplan-Meier
      analysis showed that recurrence-free survivals were not significantly different
      between Groups A and B (4-year axillary recurrence-free survival: 97.8 vs. 99.0%;
      p = 0.148). Multivariate analysis also indicated the two groups had no
      significant difference in axillary and distant recurrence-free survival.
      CONCLUSIONS: For breast cancer patients who had clinical conversion of axillary
      lymph nodes from positive to negative following neoadjuvant chemotherapy,
      sentinel biopsy-guided axillary surgery, and axillary lymph node dissection
      without sentinel lymph node biopsy had similar rates of recurrence. Thus,
      sentinel biopsy-guided axillary operation in breast cancer patients who have
      clinically axillary lymph node positive to negative conversion following
      neoadjuvant chemotherapy is a useful strategy.

PMID- 28766132
TI  - Prognostic and predictive importance of the estrogen receptor coactivator AIB1 in
      a randomized trial comparing adjuvant letrozole and tamoxifen therapy in
      postmenopausal breast cancer: the Danish cohort of BIG 1-98.
AB  - PURPOSE: To evaluate the estrogen receptor coactivator amplified in breast cancer
      1 (AIB1) as a prognostic marker, as well as a predictive marker for response to
      adjuvant tamoxifen and/or aromatase inhibitors, in early estrogen receptor
      positive breast cancer. METHOD: AIB1 was analyzed with immunohistochemistry in
      tissue microarrays of the Danish subcohort (N = 1396) of the International Breast
      Cancer Study Group's trial BIG 1-98 (randomization between adjuvant tamoxifen
      versus letrozole versus the sequence of the two drugs). RESULTS: Forty-six
      percent of the tumors had a high AIB1 expression. In line with previous studies,
      AIB1 correlated to a more aggressive tumor-phenotype (HER2 amplification and a
      high malignancy grade). High AIB1 also correlated to higher estrogen receptor
      expression (80-100 vs. 1-79%), and ductal histological type. High AIB1 expression
      was associated with a poor disease-free survival (univariable: hazard ratio 1.35,
      95% confidence interval 1.12-1.63. Multivariable: hazard ratio 1.29, 95%
      confidence interval 1.06-1.58) and overall survival (univariable: hazard ratio
      1.34, 95% confidence interval 1.07-1.68. Multivariable: hazard ratio 1.25, 95%
      confidence interval 0.99-1.60). HER2 did not seem to modify the prognostic effect
      of AIB1. No difference in treatment effect between tamoxifen and letrozole in
      relation to AIB1 was found. CONCLUSIONS: In a subset of the large international
      randomized trial BIG 1-98, we confirm AIB1 to be a strong prognostic factor in
      early breast cancer. Hence, although tumor AIB1 expression does not seem to be
      useful for the choice of tamoxifen versus an aromatase inhibitor in
      postmenopausal endocrine-responsive breast cancer, AIB1 is an interesting target
      for new anti-cancer therapies and further investigations of this biomarker is
      warranted.

PMID- 28766133
TI  - Prognostic significance of neutrophil-lymphocyte ratios in large cell
      neuroendocrine carcinoma.
AB  - OBJECTIVES: Large cell neuroendocrine carcinomas (LCNECs) are rare neuroendocrine
      pulmonary malignancies with poor survival. Towards the goal of identifying a
      useful prognostic marker for LCNEC, we examined the prognostic significance of
      the neutrophil-lymphocyte ratio (NLR) in LCNEC patients after complete resection.
      The NLR is a potential predictive indicator in other cancers and can be easily
      determined at low cost. METHODS: We retrospectively reviewed the perioperative
      clinical and laboratory data of patients who underwent complete resection for
      LCNEC between 1995 and 2014. Correlations between the preoperative NLR and
      clinicopathological parameters were determined to assess its prognostic
      significance. RESULTS: Our study consisted of 26 patients, most of whom were men
      (88.5%) with a median age of 68.8 years. The median follow-up time was 54.4
      months. Univariate analysis identified 3 clinically significant overall survival
      predictors: serum albumin level [>=4.0 g/dL (5-year overall survival rate; 80.0%)
      vs. <4.0 g/dL (30.0%), p = 0.048], pathological T stage [T1 and T2 (79.6%) vs. T3
      and T4 (0%), p = 0.001], and preoperative NLR [<1.7 (90.9%) vs. >=1.7 (51.7%), p
      = 0.012]. In a multivariate analysis, the NLR was an independent prognostic
      factor for overall survival (hazard ratio 8.559, 95% confidence interval 1.783
      80.230, p = 0.011). CONCLUSIONS: The preoperative NLR inversely correlates with
      post-resection survival rates in patients with LCNEC and thus is a viable
      prognostic marker in LCNEC.

PMID- 28766134
TI  - Bone health in long-term gastric cancer survivors: A prospective study of high
      dose vitamin D supplementation using an easy administration scheme.
AB  - Bone disease in long-term survivors after gastric cancer resection has received
      little research attention. This study aimed to investigate bone health after
      curative resection of gastric cancer and the consequences of high-dose vitamin D
      supplementation in patients with low levels of 25-(OH)-vitamin D. Disease-free
      patients at least 24 months after gastric cancer resection represented the study
      cohort. Serum markers of bone metabolism were assessed at baseline and at 3 and
      12 months. Bone mineral density and presence of fractures were assessed by X-ray
      at baseline. Patients with 25-(OH)-vitamin D <=30 ng/mL at baseline received
      16,000 IU of vitamin D3 every 10 days during the 1-year follow-up. Forty patients
      were included in the study. Mean time from surgery was 48.9 (24-109) months.
      Vitamin D insufficiency and secondary hyperparathyroidism were observed in 38 and
      20 patients, respectively. Densitometry showed osteoporosis in 14 women and seven
      men and prevalent fractures in 12 women and six men at baseline. After 3 months
      of vitamin D supplementation, 35 patients reached values of 25-(OH)-vitamin D
      over 30 ng/mL. After 12 months, 38 patients were in the normal range of 25-(OH)
      vitamin D. At the same time, iPTH levels and markers of bone turnover (C-terminal
      cross-linked telopeptide of type-I collagen, serum concentrations of bone
      specific alkaline phosphatase and osteocalcin) significantly decreased after
      vitamin D intervention. Oral administration of high doses of vitamin D is easily
      implemented and restored 25-(OH)-vitamin D and iPTH values, which are frequently
      disturbed after gastric cancer resection.

PMID- 28766135
TI  - Low serum osteocalcin concentration is associated with incident type 2 diabetes
      mellitus in Japanese women.
AB  - Increasing evidence suggests that osteocalcin is involved in the regulation of
      glucose homeostasis. However, the relationship between serum osteocalcin levels
      and risk of incident type 2 diabetes mellitus is not clear. The objective of this
      study is to investigate whether serum osteocalcin levels are associated with the
      risk of incident type 2 diabetes mellitus. This study included 1691 Japanese
      postmenopausal women, 61 incident diabetes cases, and 1630 non-diabetic control
      subjects in the observation period. Baseline concentrations of intact
      osteocalcin, HbA1c, bone-specific alkaline phosphatase, adiponectin, leptin,
      urinary N-telopeptides were assessed. Serum osteocalcin levels were significantly
      correlated with HbA1c levels among 1691 Japanese postmenopausal women (R = -0.12,
      P < 0.0001). In receiver operating characteristic curve analysis, the optimal cut
      off levels for serum osteocalcin to predict the development of type 2 diabetes
      mellitus was 6.1 ng/mL. The group with baseline osteocalcin levels <6.1 ng/mL
      showed a significantly higher risk for developing diabetes than the group with
      baseline osteocalcin levels >6.1 ng/mL (log-rank test, P  <  0.0001) during the
      mean observation period (7.6 +/- 6.1 years; mean +/- SD). In multiple Cox
      proportional hazard analysis, osteocalcin levels were significantly associated
      with development of type 2 diabetes mellitus during the observation period. Our
      results indicate that a decrease in serum osteocalcin levels is associated with
      future development of type 2 diabetes mellitus independent of conventional risk
      factors in Japanese postmenopausal women.

PMID- 28766136
TI  - Zoledronic acid and bone cellular respiration.
AB  - Phosphorescence O2 analyzer was used to measure calvarial bone cellular
      respiration (cellular mitochondrial O2 consumption) in Taylor Outbred mice in the
      presence and absence of zoledronic acid. This potent bisphosphonate inhibits
      osteoclast-mediated calcium resorption, and its effects on bone respiration have
      not been previously investigated. The change of O2 concentration with time was
      measured in closed vials containing phosphate-buffered saline (PBS), 5 mM glucose
      and 5-25 mg calvarial bone fragments, and it was complex for t = 0-30 h. Cyanide
      (specific inhibitor of cytochrome oxidase) halted O2 consumption, confirming the
      oxidation occurred in the respiratory chain. Initial rate of respiration was
      estimated from the zero-order plots d[O2]/dt for t = 0-4 h. For untreated
      specimens, the rate (mean +/- SD) was 2.0 +/- 1.2 uM O2 h-1 mg-1 (n = 6). This
      value was 7-10 times lower than that of other murine organs, but similar to that
      reported for rat and Guinea pig calvaria (averaging, 2.7 nmol O2 h-1 mg-1). The
      corresponding rate in the presence of 10-100 uM zoledronic acid was 2.7 +/- 0.7
      uM O2 h-1 mg-1 (n = 11), p = 0.216. The first-order plots ln ([O2] t  / [O2] t=0)
      versus time for t = 0-30 h were also used to compare treated and untreated
      specimens. The rate (h-1 mg-1 103) for specimens incubated in PBS without glucose
      was 1.3 +/- 0.6 (n = 3, p = 0.007), in PBS + glucose it was 10.7 +/- 6.9 (n =
      10), in PBS + glucose + 10 uM zoledronic acid it was 12.1 +/- 6.7 (n = 10, p =
      0.579), in PBS + glucose + 20 uM zoledronic acid it was 12.9 +/- 3.3 (n = 9, p =
      0.356), and in PBS + glucose + 100 uM zoledronic acid it was 13.7 +/- 7.7 (n = 9,
      p = 0.447). Thus, exposure to high-doses of zoledronic acid over several hours
      imposed a statistically insignificant increase in calvarial bone cellular
      respiration.

PMID- 28766137
TI  - Inhaled glucocorticoids are associated with vertebral fractures in COPD patients.
AB  - Chronic obstructive pulmonary disease (COPD) is an independent risk factor for
      osteoporosis. Oral glucocorticoids are deleterious to bone; however, the impact
      of inhaled glucocorticoids (ICS) remains unclear. Our objective was to determine
      whether ICS contribute to osteoporosis and fragility fractures. Sixty-one COPD
      patients, 35 current users of ICS and 26 who had never received glucocorticoids,
      were evaluated for bone mineral density (BMD) and body composition and underwent
      vertebral fracture assessment (VFA). The risk factors for bone disease considered
      for analysis were age, gender, ICS use, body mass index (BMI), muscle mass index
      (MMI), and the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      category. The Fracture Risk Assessment Tool (FRAX) calculation tool for the
      Brazilian population was also employed. The groups did not differ regarding
      gender, BMI, MMI, GOLD class, lowest values of the BMD T-score and Z-score,
      prevalence of osteoporosis, or low BMD for age. Vertebral fractures were
      identified via VFA in seven patients using ICS and in none of those not receiving
      glucocorticoids (p = 0.02). There was a trend for an association between MMI and
      osteoporosis (p = 0.05) and for a progressive decrease in the BMD Z-score
      according to the COPD severity assessed via the GOLD score (p = 0.08). Vertebral
      fractures were not associated with osteoporosis (p = 0.69) or low MMI (p = 0.12).
      The fracture risk was not estimated by FRAX. ICS may lead to bone fragility
      before a significant decrease in BMD. Low muscle mass and COPD severity may
      contribute to bone disease.

PMID- 28766138
TI  - Allogeneic yet major histocompatibility complex-matched bone marrow
      transplantation in mice results in an impairment of osteoblasts and a
      significantly reduced trabecular bone.
AB  - Secondary osteopenia following allogeneic bone marrow or stem cell
      transplantation (BMT or HSCT) is a significant source of morbidity in patients.
      It is believed to be caused by a number of factors related to the myeloablative
      conditioning and subsequent therapy regimen. We here aimed to investigate whether
      the allogeneic bone marrow by itself directly impacts on the bone mass of the
      patient. We thus performed syn- and allogeneic BMT between two inbred mouse
      strains, which share an identical major histocompatibility complex background yet
      differ in their bone phenotypes. BMT was well tolerated, yielded survival rates
      of 97% and allowed for a regular physiological development. However, allogeneic
      BMT led to a significant reduction of trabecular bone mass that was independent
      of strain, sex, immunosuppressive medication, complications resulting from graft
      versus host disease, underlying bone phenotype and numbers of osteoclasts.
      Instead, reduced trabecular bone mass correlated with reduced plasma levels of
      amino-terminal propeptide of type I collagen. Our results suggest that osteopenia
      following allogeneic BMT is significantly influenced by an impaired osteoblast
      activity that may stem from a lack of communication between the resident
      osteoblasts and an allogeneic bone marrow-derived cell type. Elucidating this
      incompatibility will open new approaches for the therapy of secondary osteopenia.

PMID- 28766139
TI  - Extracellular vesicle-mediated bone metabolism in the bone microenvironment.
AB  - Extracellular vesicles (EVs) are phospholipid membrane-enclosed entities
      containing specific proteins, RNA, miRNA, and lncRNA. EVs are released by various
      cells and play a vital role in cell communication by transferring their contents
      from the host cells to the recipient cells. The role of EVs has been
      characterized in a wide range of physiological and pathophysiological processes.
      In this context, we highlight recent advances in our understanding of the
      regulatory effects of EVs, with a focus on bone metabolism and the bone
      microenvironment. The roles of EVs in cell communication among bone-related
      cells, stem cells, tumor cells, and other cells under physiological or
      pathological conditions are also discussed. In addition, promising applications
      for EVs in treating bone-related diseases are proposed.

PMID- 28766140
TI  - Assessment of the effects of switching oral bisphosphonates to denosumab or daily
      teriparatide in patients with rheumatoid arthritis.
AB  - The aim of this observational, non-randomized study was to clarify the unknown
      effects of switching oral bisphosphonates (BPs) to denosumab (DMAb) or daily
      teriparatide (TPTD) in patients with rheumatoid arthritis (RA). The
      characteristics of the 194 female patients included in the study were 183
      postmenopausal, age 65.9 years, lumbar spine (LS) T score -1.8, femoral neck (FN)
      T score -2.3, dose and rate of taking oral prednisolone (3.6 mg/day) 75.8%, and
      prior BP treatment duration 40.0 months. The patients were allocated to (1) the
      BP-continue group (n = 80), (2) the switch-to-DMAb group (n = 74), or (3) the
      switch-to-TPTD group (n = 40). After 18 months, the increase in bone mineral
      density (BMD) was significantly greater in the switch-to-DMAb group than in the
      BP-continue group (LS 5.2 vs 2.3%, P < 0.01; FN 3.8 vs 0.0%, P < 0.01) and in the
      switch-to-TPTD group than in the BP-continue group (LS 9.0 vs 2.3%, P < 0.001; FN
      4.9 vs 0.0%, P < 0.01). Moreover, the switch-to-TPTD group showed a higher LS BMD
      (P < 0.05) and trabecular bone score (TBS) (2.1 vs -0.7%; P < 0.05) increase than
      the switch-to-DMAb group. Clinical fracture incidence during this period was 8.8%
      in the BP-continue group, 4.1% in the switch-to-DMAb group, and 2.5% in the
      switch-to-TPTD group. Both the switch-to-DMAb group and the switch-to-TPTD group
      showed significant increases in LS and FN BMD, and the switch-to-TPTD group
      showed a higher increase in TBS compared to the BP-continue group at 18 months.
      Switching BPs to DMAb or TPTD in female RA may provide some useful osteoporosis
      treatment options.

PMID- 28766141
TI  - Key role of segment IS4 in Cav1.2 inactivation: link between activation and
      inactivation.
AB  - Inactivation of L-type calcium channel (Cav1.2) is an important determinant of
      the length of the cardiac action potential. Here, we report a key role of the
      voltage-sensing segment IS4 in Cav1.2 inactivation. Neutralization of IS4 charges
      gradually shifted the steady-state inactivation curve on the voltages axis from
      5.1 +/- 3.7 mV in single point mutant IS4(K1Q) to -26.7 +/- 1.3 mV in quadruple
      mutant IS4(K1Q/R2Q/R3Q/R4Q) compared to wild-type (WT) and accelerated
      inactivation. The slope factor of the Boltzmann curve of inactivation was
      decreased from 17.4 +/- 3.5 mV (IS4(K1Q)) to 6.2 +/- 0.7 mV
      (IS4(K1Q/R2Q/R3Q/R4Q)). Neutralizations of single or multiple charges in IIS4 and
      IIIS4 did not significantly affect the time course of inactivation.
      Neutralization of individual IVS4 charges shifted the inactivation curve between
      17.4 +/- 1.7 mV (IVS4(R2Q)) and -4.6 +/- 1.4 mV (IVS4(R4Q)) on the voltage axis
      and affected the slope of the inactivation curves (IVS4(R2Q): 10.2 +/- 1.2 mV,
      IVS4(R4Q): 9.7 +/- 0.7 mV and IVS4(K5Q): 8.1 +/- 0.7 mV vs WT: 14.1 +/- 0.8 mV).
      IS4(K1Q) attenuated while IS4(K1Q/R2Q/R3Q) and IS4(K1Q/R2Q/R4Q/R3Q) enhanced the
      development of inactivation. Shifts in the voltage dependence of inactivation
      curves induced by IS4 neutralizations significantly correlated with shifts of the
      voltage dependence of channel activation (r = 0.95, p < 0.01) indicating that IS4
      movement is not only rate limiting for activation but also initiates
      inactivation. The paradoxical decrease of the slope factor of the steady-state
      inactivation and acceleration of inactivation kinetics upon charge neutralization
      in segment IS4 may reflect the loss of stabilizing interactions of arginines and
      lysine with surrounding residues.

PMID- 28766142
TI  - Phylogenetic diversity and functional characterization of the Manila clam
      microbiota: a culture-based approach.
AB  - According to the hologenome theory, the microbiota contributes to the fitness of
      the holobiont having an important role in its adaptation, survival, development,
      health, and evolution. Environmental stress also affects the microbiota and its
      capability to assist the holobiont in coping with stress factors. Here, we
      analyzed the diversity of cultivable bacteria associated with Manila clam tissues
      (mantle, gills, hemolymph) in two non-contaminated sites (Portugal and France)
      and one metal-contaminated site (Portugal). A total of 240 isolates were
      obtained. Representative isolates (n = 198) of the overall diversity were
      identified by 16S rDNA sequencing and subjected to functional characterization.
      Isolates affiliated with Proteobacteria, Actinobacteria, Firmicutes, and
      Bacteroidetes. Proteobacteria (mostly Pseudoalteromonadaceae and Vibrionaceae)
      were dominant in non-contaminated sites while Actinobacteria (mostly
      Microbacteriaceae) dominated in the metal-contaminated site. The main factor
      affecting the microbiota composition was contamination. No significant
      differences were observed between clam tissues and geographic regions. Several
      isolates tested positive for antibacterial activity, biofilm formation, protease,
      and siderophore production. The results show that the Manila clam harbors a
      diverse microbiota that may contribute to clam protection and overall fitness, as
      well as to its adaptation to stressful environments. In addition, the Manila clam
      microbiota is revealed as a promising source of novel probiotics with potential
      application in aquaculture.

PMID- 28766143
TI  - Pickling of chanterelle Cantharellus cibarius mushrooms highly reduce cadmium
      contamination.
AB  - Mushrooms are considered as potential bio-remediation agents in soil polluted
      with heavy metals, while many species which efficiently accumulate them in flesh
      are edible. Question is if there is any possible culinary use of edible mushrooms
      with high heavy metal contents? This study aimed to investigate and discuss a
      fate of cadmium (Cd) in common household-treated fruitbodies of common
      chanterelle Cantharellus cibarius. The samples of Cantharellus cibarius Fr. were
      collected from five spatially distanced sites in Poland in 2011-2012. We examined
      from 267 to 358 fruiting bodies per collection, and in total 1565 fruiting bodies
      were used. Cadmium in fungal materials from all treatments and processes
      (mushrooms dried, deep frozen, blanched and pickled) was determined using
      validated methods by inductively coupled plasma mass spectrometry with dynamic
      reaction cell. Blanching of fresh chanterelles caused decrease of Cd by around 11
      +/- 7 to 36 +/- 7%, while blanching of deep-frozen mushrooms by around 40 +/- 6%.
      A rate of Cd decrease in chanterelles was similar when the fruiting bodies were
      blanched for 5 or 15 min and when used was potable or deionized water. Pickling
      of blanched chanterelles with a diluted vinegar marinade had a pronounced effect
      on further removal of Cd. Blanched chanterelles when pickled lost an extra 37-71%
      of Cd. Total leaching rate of Cd from fresh or deep-frozen fruitbodies of
      chanterelle when blanched and further pickled was between 77 +/- 7 and 91 +/- 4%.
      Blanching and pickling highly decreased content of Cd in C. cibarius.

PMID- 28766144
TI  - Evaluation of bioaugmentation and biostimulation on arsenic remediation in soil
      through biovolatilization.
AB  - Arsenic (As) removal through microbially driven biovolatilization can be explored
      as a potential method for As bioremediation. However, its effectiveness needs to
      be improved. Biostimulation with organic matter amendment and bioaugmentation
      with the inoculation of genetic engineered bacteria could be potential strategies
      for As removal and site remediation. Here, the experiments were conducted to
      evaluate the impacts of rice straw and biochar amendment, inoculation of genetic
      engineered Pseudomonas putida KT2440 (GE P. putida) with high As volatilization
      activity, on microbial mediated As volatilization and removal from three
      different arseniferous soils. In general, the addition of rice straw (5%)
      significantly enhanced As methylation and volatilization in comparison with
      corresponding non-amended soils. Biochar amendments and inoculation of the GE P.
      putida increased As methylation and volatilization, respectively, but less than
      that of rice straw addition. The effectiveness of As volatilizations are quite
      different in the various paddy soils. The combined amendments of rice straw and
      GE P. putida exhibited the highest As removal efficiency (483.2 MUg/kg/year) in
      Dayu soil, with 1.2% volatilization of the total As annually. The highest water
      soluble As concentration (0.73 mg/kg) in this soil could be responsible for
      highest As volatilization besides the rice straw and bacteria in this soil.

PMID- 28766145
TI  - In vitro genotoxicity of asbestos substitutes induced by coupled stimulation of
      dissolved high-valence ions and oxide radicals.
AB  - The wide use of asbestos and its substitutes has given rise to studies on their
      possible harmful effects on human health and environment. However, their toxic
      effects remain unclear. The present study was aimed to disclose the coupled
      effects of dissolved high-valence ions and oxide radicals using the in vitro
      cytotoxicity and genotoxicity of chrysotile (CA), nano-SiO2 (NS), ceramic fiber
      (CF), glass fiber (GF), and rock wool (RW) on Chinese hamster lung cells V79. All
      samples induced cell mortality correlated well with the chemical SiO2 content of
      asbestos substitutes and the amount of dissolved Si. Alkali or alkaline earth
      metal elements relieved mortality of V79 cells; Al2O3 reinforced toxicity of
      materials. Asbestos substitutes generated lasting, increasing amount of acellular
      .OH which formed at the fiber surface at sites with loose/unsaturated bonds, as
      well as by catalytic reaction through dissolved iron. Accumulated mechanical and
      radical stimulation induced the intracellular reactive oxygen species (ROS)
      elevation, morphology change, and deviating trans-membrane ion flux. The cellular
      ROS appeared as NS > GF > CF ~ CA > RW, consistent with cell mortality rather
      than with acellular .OH generation. Chromosomal and DNA lesions in V79 cells were
      not directly associated with the cellular ROS, while influenced by dissolved high
      valence irons in the co-culture medium. In conclusion, ions from short-time
      dissolution of dust samples and the generation of extracellular .OH presented
      combined effects in the elevation of intracellular ROS, which further
      synergistically induced cytotoxicity and genotoxicity.

PMID- 28766146
TI  - Chemical properties of dissolved organic matter derived from sugarcane rind and
      the impacts on copper adsorption onto red soil.
AB  - Dissolved organic matter (DOM), as the most active organic carbon in the soil,
      has a coherent affinity with heavy metals from inherent and exogenous sources.
      Although the important roles of DOM in the adsorption of heavy metals in soil
      have previously been demonstrated, the heterogeneity and variability of the
      chemical constitution of DOM impede the investigation of its effects on heavy
      metal adsorption onto soil under natural conditions. Fresh DOM (FDOM) and
      degraded DOM (DDOM) from sugarcane rind were prepared, and their chemical
      properties were measured by Fourier-transform infrared spectrometry (FTIR),
      excitation-emission matrix (EEM) fluorescence spectroscopes, nuclear magnetic
      resonance (NMR), and molecular weight distribution (MWD). They were also used in
      batch experiments to evaluate their effects on the adsorption of Cu(II) onto
      farmland red soil. Based on our results, the chemical structure and composition
      of DDOM greatly varied; compared with FDOM, the C/O ratio (from 24.0 to 9.6%) and
      fluorescence index (FI) (from 1.4 to 1.0) decreased, and high molecular weight
      (>10 kDa) compounds increased from 23.18 to 70.51%, while low molecular weight
      (<3 kDa) compounds decreased from 56.13 to 12.13%; aromaticity and humification
      degree were markedly enhanced. The discrepancy of FDOM and DDOM in terms of
      chemical properties greatly influenced Cu(II) adsorption onto red soil by
      affecting DOM-Cu(II) complex capacity. The FDOM inhibited the adsorption of
      Cu(II), while DDOM promoted adsorption, which was significantly influenced by
      soil pH. Maximum adsorption capacity (Q m) was 0.92 and 5.76 mg g-1 in the
      presence of FDOM and DDOM, respectively. The adsorption process with DDOM could
      be better described by the Langmuir model, while that with FDOM was better
      described by the Freundlich model. The impacts caused by the dynamic changes of
      the chemical properties of DOM under natural conditions should therefore be
      considered in the risk assessment and remediation of soils contaminated with
      heavy metals.

PMID- 28766147
TI  - The black rock series supported SCR catalyst for NO x removal.
AB  - Black rock series (BRS) is of great potential for their plenty of valued oxides
      which include vanadium, iron, alumina and silica oxides, etc. BRS was used for
      directly preparing of selective catalytic reduction (SCR) catalyst by modifying
      its surface texture with SiO2-TiO2 sols and regulating its catalytic active
      constituents with V2O5 and MoO3. Consequently, 90% NO removal ratio was obtained
      within 300-400  degrees C over the BRS-based catalyst. The structure and
      properties of the BRS-based catalyst were characterized by the techniques of N2
      adsorption-desorption, X-ray diffraction (XRD), Raman spectroscopy, X-ray
      photoelectron spectroscopy (XPS), H2-temperature programmed reduction (H2-TPR),
      and NH3-temperature programmed desorption (NH3-TPD). The results revealed that
      the BRS-based catalyst possesses favorable properties for NO x removal, including
      highly dispersed active components, abundant surface-adsorbed oxygen Oalpha, well
      redox property, and numerous Bronsted acid sites. Particularly, the BRS-based
      catalyst exhibited considerable anti-poisoning performance compared with
      commercial TiO2-based catalyst. The former catalyst shows a NO conversion
      surpassing 80% from 300 to 400  degrees C for potassium poisoning, and a
      durability of SO2 and H2O exceeding 85% at temperatures from 300 to 450  degrees
      C.

PMID- 28766148
TI  - Biology and management of Avena fatua and Avena ludoviciana: two noxious weed
      species of agro-ecosystems.
AB  - Avena fatua and Avena ludoviciana are closely related grass weed species
      infesting a large number of crops around the world. These species are widely
      distributed in diverse agro-ecosystems from temperate to sub-tropical regions due
      to their unique seed traits, successful germination ecology, high competitive
      ability, and allelopathic potential. A. fatua is more widespread, adaptable, and
      problematic than A. ludoviciana. Both these species infest major winter and
      spring crops, including wheat, oat, barley, canola, maize, alfalfa, and
      sunflower, causing up to 70% yield losses depending on crop species and weed
      density. Chemical control has been challenged by large-scale herbicide resistance
      evolution in these weed species. A. fatua is the most widespread herbicide
      resistant weed in the world, infesting about 5 million hectares in 13 countries.
      The use of alternative herbicides with different modes of action has proved
      effective. Several cultural practices, including diverse crop rotations, cover
      crops, improved crop competition (using competitive cultivars, high seed rates,
      narrow row spacing, altered crop geometry), and allelopathic suppression, have
      shown promise for controlling A. fatua and A. ludoviciana. The integrated use of
      these cultural methods can reduce the herbicide dose required, and lower
      dependency on herbicides to control these grasses. Moreover, integrated
      management may successfully control herbicide-resistant populations of these weed
      species. The use of integrated approaches based on the knowledge of biology and
      ecology of A. fatua and A. ludoviciana may help to manage them sustainably in the
      future.

PMID- 28766149
TI  - Effects of Vacuolar H+-ATPase Inhibition on Activation of Cathepsin B and
      Cathepsin L Secreted from MDA-MB231 Breast Cancer Cells.
AB  - Studies indicate secreted cathepsins are involved in metastasis. V-ATPases, which
      are necessary for activating intracellular cathepsins, also play a role in
      metastasis and are targeted to the plasma membrane of metastatic breast cancer
      cells. We are interested in a connection between cell surface V-ATPases,
      activation of secreted cathepsins and the metastatic phenotype of MDA-MB231
      cells. We investigated whether V-ATPase inhibition would reduce the activity of
      secreted cathepsin B and cathepsin L. Using cell lysates and conditioned media,
      we measured cathepsin B and L activity within and outside of the cells. We found
      different forms of cathepsin B and L were secreted representing the pre-pro, pro
      and active forms of the proteases. Cathepsin B activity was higher than cathepsin
      L in conditioned media and in cell lysates. V-ATPase inhibition by concanamycin A
      decreased cathepsin B activity in conditioned media and significantly decreased
      cathepsin B activity in cell lysates. Cathepsin L activity showed a slight
      decrease in cell lysates. Changes in the activity of secreted and intracellular
      cathepsins following V-ATPase inhibition were supported by changes in the amounts
      of pro and active forms of cathepsin B in conditioned media and cathepsins B and
      L in cell lysates. Overall, our data shows that inactive forms of cathepsins B
      and L are secreted from the MB231 cells and V-ATPase activity is important for
      the activation of secreted cathepsin B. This indicates a connection between cell
      surface V-ATPases in metastatic breast cancer cells and the function of secreted
      cathepsin B.

PMID- 28766151
TI  - Anticoccidial effects of Artemisia annua ethanolic extract: prevention,
      simultaneous challenge-medication, and treatment.
AB  - The effect of Artemisia annua ethanolic extract (AE) as a potential source of
      herbal anticoccidial activity was investigated on experimental coccidiosis in
      chicken. One hundred ninety-two one-day-old chicks were divided in to 8 groups (n
      = 24) including AE prevention group, AE-treated group, simultaneously challenged
      AE-medicated group, challenged-untreated group (positive control), unchallenged
      untreated group (negative control), salinomycine prevention group, salinomycine
      treated group, and simultaneously challenged salinomycine-medicated group, in a
      completely randomized design. Oral challenge carried out by a suspension
      containing a mixture of 200,000 oocysts Eimeria acervulina, 30,000 oocysts
      Eimeria necatrix, and 20,000 oocysts Eimeria tenella on day 21 of age. Weight
      gain in AE prevention group significantly increased compared to positive control
      group (p < 0.05). Unlike salinomycine prevention group, the food conversion ratio
      (FCR) of AE prevention group was not significantly higher than negative control.
      Oocyst per gram (OPG) in simultaneously challenged AE-medicated group had no
      significant difference, while for 38% of the days, in simultaneously challenged
      salinomycine-medicated group significantly decreased (p < 0.05). The food intake
      of AE-treated group had no significant difference with salinomycine-treated group
      (p > 0.05). In half of the days of OPGs sampling, AE-treated group was reduced
      significantly compared to positive control group (p < 0.05). Collectively, the in
      vivo study of anticoccidial effects of AE in the prevention section was more
      effective than the treatment section, while the treatment section was more
      effective than the simultaneous section. We concluded that AE has a potential
      value to use as an herbal medicine for preventive measure in chicken coccidiosis.

PMID- 28766152
TI  - Haemosporidian prevalence and parasitaemia in the Black-throated sparrow
      (Amphispiza bilineata) in central-Mexican dryland habitats.
AB  - To date it is not well-understood how seasonality and human-induced habitat
      change may affect haemosporidian prevalence and parasitaemia in bird hosts in
      dryland habitats. We compared haemosporidian prevalence and parasitaemia between
      habitat types, including Yucca-dominated scrublands (closed habitat) and
      creosotebush scrublands (open habitat), and between seasons, including non
      breeding (dry) and breeding (wet) in the Black-throated sparrow (Amphispiza
      bilineata) at semi-arid scrublands of Central Mexico. This bird species has
      different habitat preferences in comparison to other, previously studied species
      in the region; it shows higher abundances in open than in closed habitats and
      avoids urban areas. Overall haemosporidian prevalence was 22.1%. Prevalence and
      parasitaemia were higher for Haemoproteus sp. (Parahaemoproteus sp.) than
      Plasmodium. Variation in haemoparasitism was not associated with habitat type.
      This response differs from the previously recorded response in other bird species
      in the region for which haemoparasitism increases with increasing habitat
      degradation. Seasonality seems to be the most important driver of parasite
      infection for this sparrow as prevalence and parasitaemia were higher during the
      breeding than the non-breeding season. Two new lineages of Haemoproteus sp. that
      had not been reported before in any avian species were found through molecular
      diagnosis. A high diversity of haemosporidian lineages is shared among sites.
      More study is needed to understand the mechanisms that associate parasitaemia,
      prevalence, and specific environmental factors.

PMID- 28766150
TI  - Acute and chronic neuromuscular adaptations to local vibration training.
AB  - Vibratory stimuli are thought to have the potential to promote neural and/or
      muscular (re)conditioning. This has been well described for whole-body vibration
      (WBV), which is commonly used as a training method to improve strength and/or
      functional abilities. Yet, this technique may present some limitations,
      especially in clinical settings where patients are unable to maintain an active
      position during the vibration exposure. Thus, a local vibration (LV) technique,
      which consists of applying portable vibrators directly over the tendon or muscle
      belly without active contribution from the participant, may present an
      alternative to WBV. The purpose of this narrative review is (1) to provide a
      comprehensive overview of the literature related to the acute and chronic
      neuromuscular changes associated with LV, and (2) to show that LV training may be
      an innovative and efficient alternative method to the 'classic' training
      programs, including in the context of muscle deconditioning prevention or
      rehabilitation. An acute LV application (one bout of 20-60 min) may be considered
      as a significant neuromuscular workload, as demonstrated by an impairment of
      force generating capacity and LV-induced neural changes. Accordingly, it has been
      reported that a training period of LV is efficient in improving muscular
      performance over a wide range of training (duration, number of session) and
      vibration (frequency, amplitude, site of application) parameters. The functional
      improvements are principally triggered by adaptations within the central nervous
      system. A model illustrating the current research on LV-induced adaptations is
      provided.

PMID- 28766153
TI  - Molecular cloing and bioinformatics analysis of lactate dehydrogenase from Taenia
      multiceps.
AB  - Coenurus cerebralis, the larval stage (metacestode or coenurus) of Taenia
      multiceps, parasitizes sheep, goats, and other ruminants and causes coenurosis.
      In this study, we isolated and characterized complementary DNAs that encode
      lactate dehydrogenase A (Tm-LDHA) and B (Tm-LDHB) from the transcriptome of T.
      multiceps and expressed recombinant Tm-LDHB (rTm-LDHB) in Escherichia coli.
      Bioinformatic analysis showed that both Tm-LDH genes (LDHA and LDHB) contain a
      996-bp open reading frame and encode a protein of 331 amino acids. After
      determination of the immunogenicity of the recombinant Tm-LDHB, an indirect
      enzyme-linked immunosorbent assay (ELISA) was developed for preliminary
      evaluation of the serodiagnostic potential of rTm-LDHB in goats. However, the rTm
      LDHB-based indirect ELISA developed here exhibited specificity of only 71.42%
      (10/14) and sensitivity of 1:3200 in detection of goats infected with T.
      multiceps in the field. This study is the first to describe LDHA and LDHB of T.
      multiceps; meanwhile, our results indicate that rTm-LDHB is not a specific
      antigen candidate for immunodiagnosis of T. multiceps infection in goats.

PMID- 28766154
TI  - The comparative effect of chlorine and Huwa-san as disinfecting agents on
      Biomphalaria alexandrina snails and free larval stages of Schistosoma mansoni.
AB  - Many chemicals are applied for disinfecting purposes. Although chlorination is
      the most common procedure, it has many drawbacks. So there becomes an urgent need
      for new chemicals which are both effective and less harmful to other water fauna.
      The present work aims at investigating the comparative effects of chlorine and
      Huwa-san as a new disinfectant on Biomphalaria alexandrina snails which act as
      bioindicators of toxicity, besides evaluating their miracicidal and cercaricidal
      activities. The results showed that Huwa-san was more toxic on tested snails than
      chlorine, where the LC50 values were 21 and 1368.9 ppm, respectively after 24 h.
      Also, it was found that the activities of catalase (CAT), superoxide dismutase
      (SOD), glutathione S-transferase (GST), and glutathione peroxidase (GPX) in
      snails' tissues were either induced or inhibited according to the tested
      disinfectant. Regarding reduced glutathione (GSH) content, it was increased as
      chlorine concentrations increased, while it reached its minimum content at the
      highest Huwa-san concentration. Such fluctuations were supported by
      histopathological examination of digestive and hermaphrodite glands, as prolonged
      exposure to chlorine led to more detrimental effects than Huwa-san
      concentrations. Moreover, Huwa-san was more effective on Schistosoma mansoni
      miracidia than on its cercariae, while the reverse was observed with chlorine. In
      conclusion, Huwa-san as a newly applied disinfectant can also be used as
      miracicidal and cercaricidal agent at small concentrations. Despite being more
      toxic to B. alexandrina snails, the chronic effect of its sublethal
      concentrations is less harmful than chlorine.

PMID- 28766155
TI  - A facile synthesis of amide-based receptors under microwave conditions:
      investigation of their anion recognition properties by experimental and
      computational tools.
AB  - Two novel amide-based receptors were synthesized under microwave irradiation.
      Their chemical structures were confirmed by IR, 1H NMR, 13C NMR, and elemental
      analysis. The binding properties of these amide-based receptors to various anions
      (H2PO4-, HSO4-, C6H5CO2-, CH3CO2-, ClO4-, F-, Cl-, and Br-) were examined by UV
      titration in THF at 20  degrees C. The results indicated that the receptors form
      1:1 complexes with anions and they have the strongest affinity for fluoride (F-)
      among the anions considered. Molecular dynamics calculations by AMBER and quantum
      mechanical calculations performed at the B3LYP and M062X levels of theory using
      the 6-31 + g(d,p) basis set provided models for the complexation mode between the
      receptors and anions and yielded binding energies for the complexes. Graphical
      abstract The computed interaction mode of tripodals (1a and 1b) with fluoride.

PMID- 28766156
TI  - A primer on nerve agents: what the emergency responder, anesthesiologist, and
      intensivist needs to know.
AB  - PURPOSE: The purpose of this review article is to familiarize first responders,
      anesthesiologists, and intensivists with the medical management of patients
      exposed to nerve agents. SOURCE: This review is based on the current medical
      literature available to the general medical community. PRINCIPAL FINDINGS: Nerve
      agents are some of the deadliest substances known to humanity. Though they kill
      primarily via muscle paralysis, which leads to respiratory arrest, these agents
      affect virtually every organ system in the body. Their primary mechanism of
      action is the body-wide inhibition of cholinesterases. This inhibition leads to
      the accumulation of acetylcholine, stimulating both nicotinic and muscarinic
      receptors. After decontamination, the primary treatment is with atropine to
      control muscarinic symptoms and with oximes to reactivate the cholinesterases and
      treat the nicotinic symptoms. Atropine doses can be much higher than
      conventionally used. Seizures are generally best treated with benzodiazepines.
      Patients with substantial exposure may require ventilatory and intensive care
      unit support for prolonged periods of time. CONCLUSION: While it is unlikely that
      most medical practitioners will ever encounter nerve agent poisoning, it is
      critical to be aware of the presenting symptoms and how best to treat patients
      exposed to these deadly agents. History has shown that rapid medical treatment
      can easily mean the difference between life and death for a patient in this
      situation.

PMID- 28766157
TI  - Transport Effects on Multiple-Component Reactions in Optical Biosensors.
AB  - Optical biosensors are often used to measure kinetic rate constants associated
      with chemical reactions. Such instruments operate in the surface-volume
      configuration, in which ligand molecules are convected through a fluid-filled
      volume over a surface to which receptors are confined. Currently, scientists are
      using optical biosensors to measure the kinetic rate constants associated with
      DNA translesion synthesis-a process critical to DNA damage repair. Biosensor
      experiments to study this process involve multiple interacting components on the
      sensor surface. This multiple-component biosensor experiment is modeled with a
      set of nonlinear integrodifferential equations (IDEs). It is shown that in
      physically relevant asymptotic limits these equations reduce to a much simpler
      set of ordinary differential equations (ODEs). To verify the validity of our ODE
      approximation, a numerical method for the IDE system is developed and studied.
      Results from the ODE model agree with simulations of the IDE model, rendering our
      ODE model useful for parameter estimation.

PMID- 28766158
TI  - Invasions Slow Down or Collapse in the Presence of Reactive Boundaries.
AB  - Motivated by the propagation of thin bacterial films around planar obstacles,
      this paper considers the dynamics of travelling wave solutions to the Fisher-KPP
      equation [Formula: see text] in a planar strip [Formula: see text], [Formula: see
      text]. We examine the propagation of fronts in the presence of a mixed boundary
      condition (also referred to as a 'partially absorbing' or 'reactive' boundary)
      [Formula: see text], with [Formula: see text], at [Formula: see text]. The
      presence of boundary conditions of this kind leads to the development of front
      solutions that propagate in x but contain transverse structure in y. Motivated by
      the observation that the speed of propagation in the Fisher-KPP equation is
      determined (for exponentially decaying initial conditions) by the behaviour at
      the leading edge, we analyse the linearised Fisher-KPP equation in order to
      estimate the speed of the stable travelling front, a function of the width L and
      the imposed boundary conditions. For wide strips the speed estimate based on the
      linearised equation agrees well with the results of numerical simulations. For
      narrow channels numerical simulations indicate that the stable front propagates
      more slowly, and for sufficiently small L or sufficiently large [Formula: see
      text] the front speed falls to zero and the front collapses. The reason for the
      collapse is the non-existence, far behind the front, of a stable positive
      equilibrium solution u(x, y). While existence of these equilibrium states can be
      demonstrated via phase plane arguments, the investigation of stability is similar
      to calculations of critical patch sizes carried out in similar ecological models.

PMID- 28766160
TI  - CORR Insights(r): What Are the Risk Factors and Complications Associated With
      Intraoperative and Postoperative Fractures in Total Wrist Arthroplasty?

PMID- 28766159
TI  - What is the Difference in Morphologic Features of the Thoracic Pedicle Between
      Patients With Adolescent Idiopathic Scoliosis and Healthy Subjects? A CT-based
      Case-control Study.
AB  - BACKGROUND: Describing the morphologic features of the thoracic pedicle in
      patients with adolescent idiopathic scoliosis is necessary for placement of
      pedicle screws. Previous studies showed inadequate reliability owing to small
      sample size and heterogeneity of the patients surveyed. QUESTIONS/PURPOSES: To
      use CT scans (1) to describe the morphologic features of 2718 thoracic pedicles
      from 60 female patients with Lenke Type 1 adolescent idiopathic scoliosis and 60
      age-, sex-, and height-matched controls; and (2) to classify the pedicles in
      three types based on pedicle width and analyze the distribution of each type.
      METHODS: A total of 2718 pedicles from 60 female patients with Lenke Type 1
      adolescent idiopathic scoliosis and 60 matched female controls were analyzed via
      CT. All patients surveyed were diagnosed with adolescent idiopathic scoliosis,
      Lenke Type 1, at the First Affiliated Hospital of Sun Yat-sen University, and all
      underwent pedicle screw fixation between January 2008 and December 2013 with
      preoperative radiographs and CT images on file. We routinely obtained CT scans
      before these procedures; all patients who underwent surgery during that period
      had CT scans, and all were available for analysis here. Control subjects had CT
      scans for other clinical indications and had no abnormal findings of the spine.
      The control subjects were chosen to match patients in terms of age (15 +/- 2.6
      years versus 15 +/- 2.6 years) and sex. Height of the two groups also was matched
      (154 +/- 9 cm versus 155 +/- 10 cm; mean difference, -1.06 cm; 95% CI, -1.24 to 
      0.81 cm; p < 0.001). Pedicle width and length were measured from T1 to T12. The
      thoracic spine was classified in four regions: apical vertebra in the structural
      curve (AV-SC), nonapical vertebra in the structural curve (NAV-SC), apical
      vertebra in the nonstructural curve (AV-NSC), and nonapical vertebra in the
      nonstructural curve (NAV-NSC). Pedicles were classified in three types: pedicle
      width less than 2 mm as Type I, 2 mm to 4 mm as Type II, and greater than 4 mm as
      Type III. Types I and II were defined as dysplastic pedicles. Paired t test,
      independent samples t test, one-way ANOVA, followed by Bonferroni's post hoc test
      and chi-square or Fisher's exact tests were used for statistical comparisons
      between patients and controls, as appropriate. RESULTS: No difference was found
      between pedicle width on the convex side (PWv) and in controls (PWn), but pedicle
      width on the concave side (PWc) (4.99 +/- 1.87 mm) was found to be narrower than
      PWv (6 +/- 1.66 mm) and PWn (6 +/- 1.45 mm). The variation degree of pedicle
      width (VDPW) was greatest in the AV-SC region (34% +/- 37%), in comparison to AV
      NSC (20% +/- 25%) (mean difference, 14%; 95% CI, 1.15%-27%; p = 0.025), NAV-SC
      (17% +/- 30%) (mean difference, 17%; 95% CI, 7%-27%; p < 0.001), and NAV-NSC (11%
      +/- 24%) (mean difference, 24%; 95% CI, 13%-34%; p < 0.001). Dysplastic pedicles
      appeared more in patients with adolescent idiopathic scoliosis (22%; 293 of 1322)
      compared with controls (13%; 178 of 1396) (odds ratio [OR] = 0.51; 95% CI, 0.42
      0.63; p < 0.001). In patients with adolescent idiopathic scoliosis, they commonly
      occurred on the concave side 34% (228 of 661) and on the AV-SC region (32%; 43 of
      136). CONCLUSIONS: Pedicle width on the concave side was narrower than pedicle
      width on the convex side and pedicle width in healthy control subjects. The
      apical vertebra in the structural curve was the most variegated region of the
      curve with the highest prevalence of dysplastic pedicles. CLINICAL RELEVANCE: Our
      study can help surgeons perform preoperative assessments in females with
      adolescent idiopathic scoliosis, and with preoperative and intraoperative
      management for difficult pedicle screw placement. In particular, our results
      suggest that surgeons should exercise increased vigilance when selecting pedicle
      screw dimensions, especially in the concave aspect of the mid-thoracic curve, to
      avoid cortical breeches. Future studies should evaluate other Lenke types of
      adolescent idiopathic scoliosis, and males with adolescent idiopathic scoliosis.

PMID- 28766161
TI  - Meerkats (Suricata suricatta) fail to prosocially donate food in an experimental
      set-up.
AB  - Although humans are usually believed to be prosocial, the evolutionary origins of
      prosociality are largely debated. One hypothesis is that cooperative breeding has
      been one major precursor to the emergence of prosociality. In vertebrates,
      however, experimental evidence of prosociality has been mainly gathered in non
      human primates. In this study, we tested the cooperative breeding hypothesis in
      cooperative breeding meerkats (Suricata suricatta). In particular, we tested
      whether meerkats take into account partners' benefits when distributing food
      rewards. Nine individuals were presented with two platforms baited with different
      food distributions (providing food to themselves, to a partner or both). In all
      conditions, the decision to operate the apparatus was based on the presence of
      food on the subject's side, and not on the possible benefits to partners. Despite
      being cooperative breeders, meerkats in this study failed to be prosocial,
      suggesting that prosociality in this species may be limited to specific contexts.

PMID- 28766162
TI  - Intramyocardial dissecting hematoma in anterior wall ST elevation myocardial
      infarction: impact on left ventricular remodeling and prognosis.
AB  - Intramyocardial dissecting hematoma is an uncommon complication of myocardial
      infarction potentially leading to cardiac rupture. The aim of the present study
      was to investigate coronary reperfusion results, left ventricular (LV) function
      recovery and remodeling and clinical outcomes in patients with anterior STEMI
      complicated by intramyocardial hematoma. We prospectively studied 87 patients
      (mean age 59 +/- 10 years; 88% male) with anterior STEMI (42 with intramyocardial
      hematoma) in order to evaluate coronary reperfusion results, LV remodeling (>=15%
      increase in end-systolic volume) and clinical outcomes (cardiac death, non-fatal
      reinfarction, and hospitalization for congestive heart failure) at 24 months.
      Thrombolysis in myocardial infarction (TIMI) flow score and myocardial blush
      grade (MBG) were assessed both pre- and post-percutaneous coronary intervention
      (PCI) and speckle-tracking echocardiography was performed post PCI and at 6-month
      follow-up. Patients with hematoma had lower post-PCI TIMI score and MBG, higher
      heart rate, worse LV ejection fraction and longitudinal or rotational function
      than their counterparts. LV remodeling occurred in 33 (78.6%) patients with
      hematoma and 11 (24.4%) patients without (p < 0.001). Independent predictors of
      LV remodeling were heart rate (p = 0.018), MBG (p = 0.036) and presence of
      hematoma (p < 0.001). Hematoma (log-rank test, chi2 = 9.849; p = 0.002) and LV
      remodeling (log-rank test, chi2 = 13.770; p < 0.001) were associated to a higher
      rate of adverse events. Cox analysis identified LV remodeling as the only
      independent predictor of adverse events (hazard ratio = 3.912; 95% confidence
      interval, 1.429-10.714; p = 0.008). Intramyocardial dissecting hematoma
      complicating anterior STEMI is an independent determinant of LV remodeling and is
      associated to poor prognosis.

PMID- 28766163
TI  - Seroepidemiology of echovirus 30 in Korean children.
AB  - BACKGROUND: Although aseptic meningitis associated with echovirus type 30 has
      emerged as a global public health concern, no data have been reported on
      Children's immune status against echovirus type 30. The current study aimed to
      investigate the seropositivity among Korean children for antibodies against
      echovirus 30. METHODS: Two hundred and fifty residual serum samples were
      collected at St. Paul's Hospital. Individuals were categorized by age into four
      groups: group 1 (3 months-2 years), group 2 (3-6 years), group 3 (7-10 years) and
      group 4 (11-15 years). Neutralizing antibodies against echovirus 30 were
      measured. RESULTS: Seroprotective neutralizing antibodies against echovirus 30
      were detected in 129 (49%) individuals. Seropositivity rates were 23%, 48%, 55%
      and 73% in groups 1-4, respectively. For antibody titers, 1:256-1:512 was the
      highest neutralizing antibody titer range in group 2, while 1:1024-1:2048 in
      group 3 and 4. Among the seropositive individuals in group 3 and 4, 6% and 12%
      had neutralizing antibody titers of 1:2048, respectively. CONCLUSIONS: The
      seropositivity rate increased significantly with age. The distribution of
      neutralizing antibody titers varied by age group, and higher ranges of
      neutralizing antibody titers were observed in higher age groups. These findings
      suggest high susceptibility to echovirus 30 infection in children younger than 2
      years old. Echovirus 30 infection in childhood may have contributed to increased
      neutralizing antibody titers with age.

PMID- 28766164
TI  - Effect of Aspirin and ibuprofen either alone or in combination on gastric mucosa
      and bleeding time and on serum prostaglandin E2 and thromboxane A2 levels in the
      anaesthetized rats in vivo.
AB  - There is much evidence that a combination of ibuprofen (IBU) and Aspirin (ASA)
      can antagonize the irreversible inhibition of platelet function. This study was
      designed to investigate the degree of gastric damage, bleeding time (BT) and
      fluctuations in the serum levels of prostaglandin E2 (PGE2) and thromboxane A2
      (TXA2) after oral administration of ASA (200 mg/kg) and IBU (50 mg/kg) either
      alone or in combination in rats in vivo. The stomach was assessed for any damage
      either after 6 h, 18 h or 6 days and carboxymethylcellulose (1% CMC) served as a
      vehicle and control. ELISA was used to measure TXA2 and PGE2 in serum. Bleeding
      time was assessed using tail blood. The results show that ASA and IBU either
      alone or in combination can cause gastric ulceration in 25-100% of the rats at 6
      and 18 h. In contrast, gastric ulceration was seen in 50% of rats with a
      combination of ASA given before IBU only after 6 days of oral administration. BT
      was unaffected either by ASA or IBU when administered alone except after 18 h for
      IBU. In contrast, BT was significantly reduced when IBU was administered before
      ASA after 18 h and 6 days (P < 0.001). Serum PGE2 levels decreased significantly
      after ASA administered either alone or in combination with IBU for 6 h, 18 h and
      6 days (P < 0.05). Serum TXA2 levels were significantly reduced after 6 h, 18 h
      and 6 days following ASA and IBU administration except for IBU alone which caused
      a significant increase in serum TXA2 6 days after its administration (P < 0.01).
      It can be concluded that ASA and IBU administered either alone or in combination
      can cause gastric ulcers in the rat stomach after 6 h and 18 h, but less severe
      after 6 days. IBU either alone or in combination with ASA reduced BT only after
      18 h and 6 days of administration. Together, the results show that gastric
      ulceration correlated well with the inhibition of serum PGE2 and TXA2 levels.

PMID- 28766165
TI  - Chagas disease: modulation of the inflammatory response by acetylcholinesterase
      in hematological cells and brain tissue.
AB  - Chagas disease is an acute or chronic illness that causes severe inflammatory
      response, and consequently, it may activate the inflammatory cholinergic pathway,
      which is regulated by cholinesterases, including the acetylcholinesterase. This
      enzyme is responsible for the regulation of acetylcholine levels, an anti
      inflammatory molecule linked to the inflammatory response during parasitic
      diseases. Thus, the aim of this study was to investigate whether Trypanosoma
      cruzi infection can alter the activity of acetylcholinesterase and acetylcholine
      levels in mice, and whether these alterations are linked to the inflammatory
      cholinergic signaling pathway. Twenty-four mice were divided into two groups:
      uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12).
      The animals developed acute disease with a peak of parasitemia on day 7 post
      infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post
      infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase
      activity, and histopathology were analyzed. In total blood and brain,
      acetylcholinesterase activity decreased at both times. On the other hand,
      acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with
      the control group. Infection by T. cruzi increased acetylcholine and nitric oxide
      levels and histopathological damage in the brain of mice associated to increased
      myeloperoxidase activity. Therefore, an intense inflammatory response in mice
      with acute Chagas disease in the central nervous system caused an anti
      inflammatory response by the activation of the cholinergic inflammatory pathway.

PMID- 28766166
TI  - rhPDGF-BB combined with ADSCs in the treatment of Achilles tendinitis via miR
      363/PI3 K/Akt pathway.
AB  - To investigate the mechanism of recombinant human platelet-derived growth factor
      BB (rhPDGF-BB) and human adipose-derived stem cells (hADSCs) in the treatment of
      Achilles tendinitis. Biomechanical indices of stiffness, stress, and maximum load
      to-failure were detected by biomechanical test. mRNA and protein levels of miR
      363, p-PI3K/AKT, tendon-related genes Collagen I, Scleraxis (Scx), and Tenascin C
      (TNC) were measured by qRT-PCR and western blot. The proliferation of hADSCs was
      accessed by MTT assay. Biomechanical indices of stiffness, stress, and maximum
      load-to-failure, and mRNA and protein levels of tendon-related genes could be
      improved by rhPDGF-BB or hADSCs alone, and could be further improved by rhPDGF-BB
      + hADSCs. rhPDGF-BB and hADSCs downregulated the expression of miR-363 and
      upregulated the levels of p-PI3K/Akt, and rhPDGF-BB + hADSCs further strengthened
      these effects. In addition, rhPDGF-BB promoted the proliferation of hADSCs in
      vitro and upregulated the expression of tendon-related genes. miR-363 mimic
      downregulated the levels of p-PI3K/Akt, miR-363 inhibitor upregulated the levels
      of p-PI3K/Akt, and miR-363 mimic and PI3K/Akt pathway inhibitor LY294002 reversed
      the positive effect of rhPDGF-BB on the proliferation of hADSCs, which suggested
      that rhPDGF-BB promoted the proliferation of hADSCs via miR-363/PI3K/Akt pathway.
      Biomechanical indices and tendon-related genes could be improved by rhPDGF-BB and
      hADSCs. Moreover, rhPDGF-BB promoted the proliferation of hADSCs via miR
      363/PI3K/Akt pathway, indicating that rhPDGF-BB combined with ADSCs could treat
      Achilles tendinitis via miR-363/PI3K/Akt pathway.

PMID- 28766167
TI  - A novel guaiane sesquiterpene derivative, guai-2-en-10alpha-ol, from Ulva
      fasciata Delile inhibits EGFR/PI3K/Akt signaling and induces cytotoxicity in
      triple-negative breast cancer cells.
AB  - A novel guaiane sesquiterpene derivative, guai-2-en-10alpha-ol, from Ulva
      fasciata Delile exhibits antimicrobial property. U. fasciata extract was reported
      to exhibit cytotoxicity against cancer. In the present study, we have studied the
      anticancer potential of the compound, guai-2-en-10alpha-ol, from U. fasciata. The
      compound showed selective cytotoxicity toward triple-negative breast cancer
      (TNBC) cell line (MDA MB-231) in a dose-dependent manner. In treated cells, the
      apoptotic hallmarks such as formation of apoptotic bodies, cell shrinkage, and
      nuclear condensation were observed. Many small molecules affect the function of
      cellular signaling pathways. As EGFR/PI3K/Akt pathway proteins are frequently
      altered in TNBC, we have studied the gene expression of key proteins of this
      pathway. The semiquantitative PCR results demonstrated the down-regulated
      expression of PDPK1 (positive regulator) and Akt (key activator) as well as up
      regulated expression of PTEN (negative regulator), which suggested the
      interaction of guai-2-en-10alpha-ol with upstream protein. Further investigation
      showed the down-regulation of both PI3K and EGFR. As EGFR is the most upstream
      protein of the pathway, its protein level expression was investigated. Western
      blotting analysis confirmed the down-regulation of p-EGFR expression and
      activation of apoptosis upon compound treatment. Cell cycle analysis also
      evidenced the G1 phase arrest, which can be due to the inhibition of cell
      survival pathway. Computational studies showed the interaction of guai-2-en
      10alpha-ol with Asp855 residue of EGFR kinase domain in active conformation. All
      these results demonstrate the anticancer potential of guai-2-en-10alpha-ol
      through EGFR/PI3K/Akt pathway.

PMID- 28766168
TI  - Pre- and post-prandial expression of genes involved in lipid metabolism at the
      end of the overfeeding period of mule ducks.
AB  - In palmipeds, overfeeding leads to hepatic steatosis, also called "foie gras"
      which is the result of many metabolic mechanisms. In order to understand these
      mechanisms, we decided to measure the expression of genes implicated in lipid
      metabolism during 12 hours (h) following the last meal of the overfeeding period.
      We have shown that there is a precocious expression (within 2 h) of fatty acid
      synthase and acyl CoA synthetase long-chain 1 in liver and muscle of mule ducks
      in addition with a later peak. Furthermore, di-acyl glycerol acyl transferase
      presents the highest induction of expression in liver and it is overexpressed
      quite a long time, positioning this enzyme as a key factor in hepatic steatosis.
      These observations are quite similar in muscle. Lipoprotein secretion is
      upregulated later in postprandial period, with an upregulation of apolipoprotein
      and microsomal triglycerides transfer protein beginning at 5 h in liver or
      muscle. Regarding hepatic re-uptake of lipid, lesser variations are observed,
      suggesting that fatty acid binding protein and very low-density lipoprotein
      receptor (VLDLR) are already at their maximum expression specifically in these
      tissues. In muscle, VLDLR and LDLR upregulation is observed 5 h after the meal,
      associated with an overexpression in the adipose tissue of lipase maturation
      factor 1 involved in the maturation of lipoprotein lipase. These findings will
      allow us to better understand the kinetic treatment in lipid metabolism after a
      meal in overfed ducks. This first report on kinetic expression will allow
      researcher to better target their sampling time knowing the optimal point of
      expression of each gene.

PMID- 28766169
TI  - Retinoid acid and taurine promote NeuroD1-induced differentiation of induced
      pluripotent stem cells into retinal ganglion cells.
AB  - Induced pluripotent stem cells (iPSCs) possess the capacity to differentiate into
      multiple cell types including retinal neurons. Despite substantial progress in
      the transcriptional regulation of iPSC differentiation process, the efficiency of
      generation of retinal neurons from iPSCs is still low. In this study, we
      investigated the role of transcription factor NeuroD1 in the differentiation of
      iPSCs into retinal neurons. We observed that retrovirus-mediated NeuroD1
      overexpression in iPSCs increased the efficiency of neuronal differentiation.
      Immunostaining analysis showed that NeuroD1 overexpression increased the
      expression of retina ganglion cell markers including Islet-1, Math5, Brn3b, and
      Thy1.2. Retinoid acid (RA) and taurine further improved the differentiation
      efficiency of iPSCs overexpressing NeuroD1. However, RA and taurine did not
      promote differentiation in the absence of NeuroD1 overexpression. Together, our
      study provides new evidence in transcription factor-regulated stem cell
      differentiation in vitro.

PMID- 28766170
TI  - Aegle marmelos differentially affects hepatic markers of glycolysis, insulin
      signalling pathway, hypoxia, and inflammation in HepG2 cells grown in fructose
      versus glucose-rich environment.
AB  - Fructose consumption is responsible for the onset of insulin resistance (IR), and
      metabolic syndrome. It possesses no functional utility in body and its
      detrimental effects on hepatic metabolic milieu are beyond those produced by
      glucose. The need of the hour is to identify fructose-induced IR as an unique
      pathological state to be managed differentially. The effect of aqueous leaf
      extract of Aegle marmelos (AM) on hepatic markers of insulin resistance using
      HepG2 cells cultured in either fructose or glucose-rich environment is
      investigated. Human hepatocellular carcinoma cells (HepG2) were grown under
      standard conditions in either-DMEM without glucose (NC), DMEM with high glucose
      25 mM (Glu), DMEM-glucose+0.55 mM fructose (FC1), DMEM-glucose+1 mM fructose
      (FC2) or DMEM-glucose+1 mM fructose+0.1 uM insulin (FC3). The cells were treated
      with either AM, rutin, quercetin, metformin or pioglitazone and assessed for
      levels of hexokinase, phosphofructokinase (PFK), aldehyde dehydrogenase,
      phosphatidylinositol kinase (PI3K), signal transducer and activator of
      transcription-3 (STAT-3), mitochondrial target of rapamycin (mTOR), hypoxia
      induced factor (HIF-1alpha), vascular endothelial growth factor (VEGF) and tumour
      necrosis factor (TNF-alpha). Summarily, when results from fructose- and glucose
      rich environment were compared, then (1) IR was more pronounced in former; (2) AM
      performed better in former; (3) metformin and pioglitazone were equivocal in
      either; (4) rutin and quercetin showed deviant effects from AM; and lastly (5)
      effects of rutin were closer to AM than quercetin. We hypothesize that AM
      ameliorates fructose-induced IR through a mechanism which is distinct from
      standard drugs and not shared by individual phytoconstituents in toto.

PMID- 28766171
TI  - Cisplatin and cisplatin analogues perfusion through isolated rat heart: the
      effects of acute application on oxidative stress biomarkers.
AB  - Drug-induced oxidative stress can occur in numerous tissues and organ systems
      (liver, kidney, ear, nervous system, and cardiovascular system). Cancer therapy
      with cisplatin is associated with side effects to which oxidative stress may
      contribute. We have compared the influences of cisplatin (reference compound) and
      its' analogues (dichloro(1,2-diaminocyclohexane)platinum(II) and
      chloro(2,2':6',2"-terpyridine)platinum(II)) in a model of isolated rat heart
      using the Langendorff technique. The production of oxidative stress biomarkers,
      antioxidant enzymes, myocardial damage, and expression of Bax, OH-1, and SODs
      were studied. Cisplatin and the analogues were perfused at concentration of 10-6
      and 10-5 M during 30 min. The results of this study showed that examined platinum
      complexes had different ability to induce oxidative stress of isolated perfused
      rat heart. Varying the carrier ligands, such as 1,2-diaminocyclohexane and
      2,2':6',2"-terpyridine, related to amino ligands (cisplatin) directly influenced
      the strength to induce production of oxidative stress biomarkers. Introducing
      2,2':6',2"-terpyridine ligands provoked the smallest changes in antioxidant
      enzymes activity, lipid peroxidation, and expression of heme oxygenase-1, that
      undoubtedly indicated that this complex had the lowest impact on redox status in
      heart tissue. These findings may be useful in synthesis of novel platinum
      analogues with lower potential for oxidative stress induction. However, the fact
      that platinum complexes could induce toxic effects in the heart by other
      mechanisms should be taken into the consideration.

PMID- 28766172
TI  - Sustainable urban systems: Co-design and framing for transformation.
AB  - Rapid urbanisation generates risks and opportunities for sustainable development.
      Urban policy and decision makers are challenged by the complexity of cities as
      social-ecological-technical systems. Consequently there is an increasing need for
      collaborative knowledge development that supports a whole-of-system view, and
      transformational change at multiple scales. Such holistic urban approaches are
      rare in practice. A co-design process involving researchers, practitioners and
      other stakeholders, has progressed such an approach in the Australian context,
      aiming to also contribute to international knowledge development and sharing.
      This process has generated three outputs: (1) a shared framework to support more
      systematic knowledge development and use, (2) identification of barriers that
      create a gap between stated urban goals and actual practice, and (3)
      identification of strategic focal areas to address this gap. Developing
      integrated strategies at broader urban scales is seen as the most pressing need.
      The knowledge framework adopts a systems perspective that incorporates the many
      urban trade-offs and synergies revealed by a systems view. Broader implications
      are drawn for policy and decision makers, for researchers and for a shared
      forward agenda.

PMID- 28766173
TI  - Clinical features and long-term outcomes of pediatric intraventricular
      meningiomas: data from a single neurosurgical center.
AB  - The purpose of this study is to investigate the clinical characteristics and long
      term outcomes of pediatric patients with intraventricular meningioma. We
      retrospectively analyzed a total of 30 pediatric patients with intraventricular
      meningiomas who were surgically treated at our department between January 2005
      and June 2016 and analyzed their clinical characteristics and surgical outcomes.
      Among the 160 pediatric patients with intracranial meningioma, 33 (20.6%) had
      intraventricular lesions. However, only 30 patients had complete demographic and
      clinical data. A male predilection (male/female = 1.5:1) was observed, and the
      mean age of our patient cohort was 12.6 years. The lateral ventricle was the most
      common lesion site (88.6%). In addition, the most common initial symptom was
      headache or dizziness, and the average interval from symptom onset to admission
      was 19.17 months (0.25-72 months). Twenty-six patients (86.7%) achieved a Simpson
      grade of I. Based on the WHO classification, 28 (93.3%) meningiomas were
      classified as grade I, and the remaining two cases were grades II and III. During
      the follow-up period (0.67-10.08 years), 3 patients experienced tumor recurrence
      (15, 18, and 83 months, respectively), and 1 patient died of recurrence.
      Pediatric and adult intraventricular meningiomas present similar clinical
      characteristics and surgical outcomes; however, intraventricular meningiomas
      compose a higher percentage of pediatric meningiomas and have a male
      predilection. Compared with general pediatric meningiomas, pediatric
      intraventricular meningiomas tend to have higher incidence of benign subtypes.
      They are also more likely to be completely resected and have lower recurrence and
      mortality rates.

PMID- 28766174
TI  - Discriminant Analysis of Intracranial Volumetric Variables in Patients with
      Normal Pressure Hydrocephalus and Brain Atrophy.
AB  - A method was developed for the computerized volumetric assessment of the
      intracranial cerebrospinal fluid (CSF) distribution. The study involved 62
      patients differentiated into two groups: with CSF resorption disorders (normal
      pressure hydrocephalus - 30 patients) and without CSF resorption disorders
      (various types of brain atrophy - 32 patients). The goal of the study was to
      ascertain whether the assessment, depending on the linear discriminant analysis
      of volumetric brain features, could be an effective tool differentiating the two
      groups. Volumetric measurements were performed using VisNow software. For each
      patient, five features were determined and subjected to discriminant analysis:
      CSF volume in the subarachnoid space and basal cisterns (SV), CSF volume in the
      intracranial ventricular system (VV), brain volume (BV), total intracranial CSF
      volume (FV), and total intracranial volume (TV). Discriminant analysis enables
      the achievement of a high percentage of correct classification of patients to the
      appropriate group determined on the result of a lumbar infusion test. The
      discriminator, based on three features: BV, SV, and VV, showed a complete
      separation of the groups; irrespective of age. The squared Mahalanobis distance
      was 70.8. The results confirmed the applicability of the volumetric method.
      Discriminant analysis seems a useful tool leading to the acquisition of a
      computer-aided method for the differential diagnosis of CSF resorption disorders.

PMID- 28766175
TI  - Backbone and side chain resonance assignments for a structured domain within
      Atg32.
AB  - Autophagy is a catabolic cellular process that targets cytosolic material,
      including mitochondria, to the vacuole or lysosomes for degradation. The
      selective degradation of mitochondria by autophagy is termed mitophagy.
      Dysfunctional mitophagy, which leads to the accumulation of damaged mitochondria,
      has been implicated in Parkinson's disease, cancer, cardiac disease and metabolic
      disease. In Saccharomyces cerevisiae, mitophagy is initiated by the autophagy
      receptor Atg32, an outer mitochondrial membrane protein. A lack of structural
      information for Atg32 has hindered our understanding of the molecular mechanisms
      of mitophagy initiation. To gain new structural insight into Atg32, we have
      identified the location of a structured domain within the cytosolic region of
      Atg32 and completed the backbone and side chain resonance assignments for this
      domain.

PMID- 28766176
TI  - Play-Modified One-Session Treatment for Young Children with a Specific Phobia of
      Dogs: A Multiple Baseline Case Series.
AB  - The one-session treatment (OST) approach for SPs is deemed well-established, and
      has been found to be highly effective for older children and adults; however, has
      not yet been trialled with very young children. The present study examines the
      preliminary effectiveness of play-modified OST for young children with a SP of
      dogs, using a multiple baseline controlled case series design. Treatment involved
      play modified one-session of intensive cognitive-behavioural therapy (OST plus
      Play) which was followed by brief telephone delivered maintenance calls over the
      3 weeks immediately following treatment. Four young children (4 years of age)
      participated and symptoms were assessed at pre-treatment, across a 1-3 week
      baseline phase, immediately following the OST plus Play, and at 1 and 3 months
      follow-up. Visual inspection provided evidence for stability of symptoms across
      the baseline phase, followed by reductions in symptoms over the course of
      treatment and follow-up. Non-parametric analyses offered further support, with
      significant improvements in following the intensive OST plus Play intervention.

PMID- 28766177
TI  - Using needle orientation sensing as surrogate signal for respiratory motion
      estimation in percutaneous interventions.
AB  - PURPOSE: To develop and evaluate an approach to estimate the respiratory-induced
      motion of lesions in the chest and abdomen. MATERIALS AND METHODS: The proposed
      approach uses the motion of an initial reference needle inserted into a moving
      organ to estimate the lesion (target) displacement that is caused by respiration.
      The needles position is measured using an inertial measurement unit (IMU) sensor
      externally attached to the hub of an initially placed reference needle. Data
      obtained from the IMU sensor and the target motion are used to train a learning
      based approach to estimate the position of the moving target. An experimental
      platform was designed to mimic respiratory motion of the liver. Liver motion
      profiles of human subjects provided inputs to the experimental platform.
      Variables including the insertion angle, target depth, target motion velocity and
      target proximity to the reference needle were evaluated by measuring the error of
      the estimated target position and processing time. RESULTS: The mean error of
      estimation of the target position ranged between 0.86 and 1.29 mm. The processing
      maximum training and testing time was 5 ms which is suitable for real-time target
      motion estimation using the needle position sensor. CONCLUSION: The external
      motion of an initially placed reference needle inserted into a moving organ can
      be used as a surrogate, measurable and accessible signal to estimate in real-time
      the position of a moving target caused by respiration; this technique could then
      be used to guide the placement of subsequently inserted needles directly into the
      target.

PMID- 28766178
TI  - Differential Regulation of IL-1beta and IL-6 Release in Murine Macrophages.
AB  - Asbestos and silica (exogenous danger) and adenosine triphosphate (ATP,
      endogenous danger-signaling molecule) synergistically increase IL-1beta release
      from endotoxin-primed macrophage, which is mediated by NOD-like receptor protein
      3 (NLRP3) inflammasome. However, the conversion of pro-IL-1beta to its active
      form seems to depend on the macrophage cell types. In the present study, bone
      marrow-derived macrophages (BMM) and three murine macrophage cell lines, J774.1,
      J774A.1, and RAW264.7 were exposed to ATP or fibrous titanium dioxide (FTiO2) in
      the presence or absence of lipopolysaccharide (LPS), and the concentrations of IL
      1beta and IL-6 in both cell lysates and in the culture media were measured by
      immunoblotting to differentiate active form of IL-1beta from pro-IL-1beta. IL
      1beta release was synergistically increased when the cells were exposed to both
      LPS and ATP or FTiO2, while IL-6 was readily released by LPS alone. IL-1beta
      released into the culture medium was pro-IL-1beta in J774.1 and RAW264.7, and
      most of the pro-IL-1beta remained inside the cells. In contrast, the active form
      of IL-1beta was released together with pro-IL-1beta from J774A.1 and BMM after
      the co-stimulation. J774A.1 and BMM express apoptosis-associated speck-like
      protein contains a carboxyl-terminal CARD (ASC) while J774.1 and RAW264.7 do not
      or only faintly express ASC, and accordingly, caspase-1, which converts pro-IL
      1beta to its active form, is activated only in J774A.1 and BMM. Collectively, the
      canonical inflammasome pathway is not activated in J774.1 and RAW264.7, and the
      apparent synergistical increase of IL-1beta in the culture medium mostly reflects
      the leakage of pro-IL-1beta from these cells.

PMID- 28766179
TI  - Glutaric Aciduria Type 3: Three Unrelated Canadian Cases, with Different Routes
      of Ascertainment.
AB  - Glutaric aciduria type 3 (GA3) is associated with decreased conversion of free
      glutaric acid to glutaryl-coA, reflecting deficiency of succinate
      hydroxymethylglutarate coA-transferase, caused by variants in the SUGCT (C7orf10)
      gene. GA3 remains less well known, characterised and understood than glutaric
      aciduria types 1 and 2. It is generally considered a likely "non-disease," but
      this is based on limited supporting information, with only nine individuals with
      GA3 described in the literature. Clinicians encountering a patient with GA3
      therefore still face a dilemma of whether or not this should be dismissed as
      irrelevant.We have identified three unrelated Canadian patients with GA3. Two
      came to clinical attention because of symptoms, while the third was identified by
      a population urine-based newborn screening programme and has so far remained
      asymptomatic. We describe the clinical histories, biochemical characterisation
      and genotypes of these individuals. Examination of allele frequencies underlines
      the fact that GA3 is underdiagnosed. While one probable factor is that some GA3
      patients remain asymptomatic, we highlight other plausible reasons whereby this
      diagnosis might be overlooked.Gastrointestinal disturbances were previously
      reported in some GA3 patients. In one of our patients, severe episodes of cyclic
      vomiting were the major problem. A trial of antibiotic treatment, to minimise
      bacterial GA production, was followed by significant clinical improvement.At
      present, there is insufficient evidence to define any specific clinical phenotype
      as attributable to GA3. However, we consider that it would be premature to assume
      that this condition is completely benign in all individuals at all times.

PMID- 28766180
TI  - The expression of water channel proteins during human salivary gland development:
      a topographic study of aquaporins 1, 3 and 5.
AB  - Some members of aquaporin family (AQP) plays crucial functions in salivary
      synthesis and secretion. These proteins expression has already been reported
      during salivary gland formation, however no previous studies in human developing
      glands have been performed. We evaluated AQP1, 3 and 5 expression through the
      stages of human salivary gland morphogenesis and discuss the possible role of AQP
      for glandular maturation. Human salivary glands derived from foetuses aged
      between 14 and 25 weeks were submitted to immunohistochemistry. At the bud stage,
      membrane expression of AQP1, 3 and 5 were observed within the epithelial bud
      cells presenting a similar apicolateral pattern, also found at the
      pseudoglandular stage, present within the terminal portions of future acini,
      while AQP5 was also particularly strong at the apical membrane of pre-acinar and
      pre-ductal cells. AQP5 was co-localised with Cytokeratin 7. Similar AQP1, 3 and 5
      expression were observed at the following canalicular stage, where distinct and
      strongly luminal and acinar AQP5 expression is present. During the final terminal
      bud stage, AQP1 was only identified in serous acini, myoepithelial and
      endothelial cells, while differentiated mucous acinar cells and ducts were
      negative. AQP3 was detected at apicolateral membranes of both mucous and serous
      acini. AQP5 also showed a diffuse expression in mucous and serous acini, in
      addition to strong apical membrane expression within lumen of intercalated ductal
      cells. This topographic analysis of AQP1, 3 and 5 revealed differences in the
      expression pattern throughout salivary gland developmental stages, suggesting
      different roles for each protein in human glandular maturation.

PMID- 28766181
TI  - Treatment of Amlodipine Intoxication with Intravenous Lipid Emulsion Therapy: A
      Case Report and Review of the Literature.
AB  - We report the case of a 25-year-old female presenting to the emergency department
      after committing suicide by ingesting 100 mg amlodipine. The patient was
      initially treated with intravenous fluids, calcium gluconate, catecholamines and
      glucagone without effect. The clinical condition of the patient improved quickly
      and dramatically on the 20th minute of intravenous lipid emulsion (ILE) therapy.
      Different treatment methods have been developed for calcium channel blocker
      intoxication over the last years. Among these, lipid emulsion therapy has risen
      over the last decade as a salvation in cases which do not respond to other
      treatments. However, given the paucity of data, there are conflicting
      recommendations about the indications, dose and timing of ILE in the literature.
      In the light of this case report, we review the literature and discuss whether
      ILE therapy can find itself a place among first-line therapy recommendations.

PMID- 28766182
TI  - Lipidomics and anti-trypanosomatid chemotherapy.
AB  - BACKGROUND: Trypanosomatids such as Leishmania, Trypanosoma brucei and
      Trypanosoma cruzi belong to the order Kinetoplastida and are the source of many
      significant human and animal diseases. Current treatment is unsatisfactory and is
      compromised by the rising appearance of drug resistant parasites. Novel and more
      effective chemotherapeutics are urgently needed to treat and prevent these
      devastating diseases, which relies on the identification of essential, parasite
      specific targets that are absent in the host. Lipids constitute essential
      components of the cell and carry out multiple critical functions from building
      blocks of biological membranes to regulatory roles in signal transduction,
      organellar biogenesis, energy storage, and virulence. The recent technological
      advances of lipidomics has facilitated the broadening of our knowledge in the
      field of cellular lipid content, structure, functions, and metabolic pathways.
      MAIN BODY: This review highlights the application of lipidomics (i) in the
      characterization of the lipidome of kinetoplastid parasites or of their
      subcellular structure(s), (ii) in the identification of unique lipid species or
      metabolic pathways that can be targeted for novel drug therapies, (iii) as an
      analytic tool to gain a deeper insight into the roles of specific enzymes in
      lipid metabolism using genetically modified microorganisms, and (iv) in
      deciphering the mechanism of action of anti-microbial drugs on lipid metabolism.
      Lastly, an outlook stating where the field is evolving is presented. CONCLUSION:
      Lipidomics has contributed to the expanding knowledge related to lipid
      metabolism, mechanism of drug action and resistance, and pathogen-host
      interaction of trypanosomatids, which provides a solid basis for the development
      of better anti-parasitic pharmaceuticals.

PMID- 28766183
TI  - Guided imagery targeting exercise, food cravings, and stress: a multi-modal
      randomized feasibility trial.
AB  - The purpose of this randomized wait-list controlled trial was to test the
      feasibility and preliminary efficacy of a guided imagery based multi-behavior
      intervention intended to address psychological stress, food cravings, and
      physical activity. Personalized guided imagery scripts were created and
      participants were instructed to practice guided imagery every day for 35
      consecutive days. Of 48 women who enrolled, we report comparisons between 16
      randomized to treatment with 19 who were wait-listed (overall Mage = 45.50;
      Mbodymassindex = 31.43). Study completers reported 89% compliance with practicing
      guided imagery during the intervention. A significant time-by-group interaction
      was observed with reductions in food cravings and increases in physical activity
      compared with wait-list controls. Telephone-based multi-behavior interventions
      that utilize guided imagery to address food cravings and exercise behavior appear
      to be acceptable for overweight and obese women. Future phone-based guided
      imagery research testing this skill to address multiple health behaviors is
      justified.

PMID- 28766185
TI  - When your mind skips what your eyes fixate: How forced fixations lead to
      comprehension illusions in reading.
AB  - The phenomenon of forced fixations suggests that readers sometimes fixate a word
      (due to oculomotor constraints) even though they intended to skip it (due to
      parafoveal cognitive-linguistic processing). We investigate whether this leads
      readers to look directly at a word but not pay attention to it. We used a gaze
      contingent boundary paradigm to dissociate parafoveal and foveal information
      (e.g., the word phone changed to scarf once the reader's eyes moved to it) and
      asked questions about the sentence to determine which one the reader encoded.
      When the word was skipped or fixated only briefly (i.e., up to 100 ms) readers
      were more likely to report reading the parafoveal than the fixated word,
      suggesting that there are cases in which readers look directly at a word but
      their minds ignore it, leading to the illusion of reading something they did not
      fixate.

PMID- 28766184
TI  - Frequency and Nature of Adverse Drug Reactions Due to Non-Prescription Drugs in
      Children: A Retrospective Analysis from the French Pharmacovigilance Database.
AB  - INTRODUCTION: Studies that evaluate the safety of non-prescription drugs in
      children remain scarce. OBJECTIVES: The aim of the present study was to compare
      adverse drug reactions (ADRs) due to prescription versus non-prescription drugs
      in children. METHODS: We conducted a retrospective analysis of ADR notifications
      for a pediatric population (aged <18 years) registered in the French
      PharmacoVigilance Database (FPVD) between January 1985 and December 2016 by the
      Midi-Pyrenees PharmacoVigilance Center (in the south of France). We compared ADR
      profiles according to drug prescription status using a Chi-squared test. RESULTS:
      We included 2218 notifications concerning 3687 ADRs in the study. Non
      prescription drugs were involved in 506 notifications (22.8%). Patients were
      younger in the non-prescription drug group (6.7 +/- 5.3 vs. 8.4 +/- 5.7 years in
      the prescription drug group). No difference by sex was found. Neurological ADRs
      were more frequent with prescription drugs (21.0%) than with non-prescription
      drugs (14.2%, p = 0.0008), whereas dermatological disorders (37.2 vs. 29.1%,
      respectively) and general ADRs (30.8 vs. 20.1%, respectively) were more frequent
      with non-prescription than with prescription drugs (p = 0.0006 and p < 0.0001,
      respectively). The frequency of "serious" ADRs was higher with prescription drugs
      than with non-prescription drugs (40.9 vs. 34.2%, p = 0.007). The non
      prescription drugs most frequently implicated with serious ADRs were ibuprofen (n
      = 37; 4.2%), tuberculosis vaccine (n = 23; 2.6%), aspirin (n = 20, 2.3%), and
      paracetamol (n = 17; 1.9%). ADRs from prescription drugs involved asparaginase (n
      = 27; 3.1%), immunoglobulins (n = 25; 2.9%), and amoxicillin (n = 23; 2.4%).
      CONCLUSIONS: Non-prescription drugs, usually considered safe, were frequently
      responsible for ADR notifications. The non-prescription medication most
      frequently involved in serious ADRs was ibuprofen.

PMID- 28766186
TI  - Transformation of intimacy and its impact in developing countries.
AB  - Nowadays intimacy or intimate relationship is very familiar and widely used term
      all over the world. The term 'Intimacy' generally denotes a close interpersonal
      relationship or feeling of being in a close personal association and belonging
      together from both physical and mental point of view. It also denotes very close
      and effective connection with one another which may exist for whole life or may
      not. This article has been prepared on the basis of secondary sources and it
      tries to explore how this intimacy or intimate relationship has been gradually
      transforming from pre-modern society to modern society and from modern society to
      post-modern society for over the eras. This article also tries to explore the
      impact of transformed intimacy or intimate relationship, especially in the
      developing countries, like Bangladesh. Intimate relationship plays very
      significant role in the overall life style of any human being. This relationship
      includes feelings of liking, romance, sexuality or sexual relationship, emotional
      or personal support between mates. But the role of sexuality or sexual
      relationship is gradually increasing in intimacy, not only in the western
      countries but also in the developing countries. Nowadays people are involved with
      many kinds of premarital and extramarital relationships and they try to avoid the
      risk of reproduction. This tendency creates many problems in the developing
      countries, as most of the people of such developing countries are poor and
      illiterate. They are not aware about the dangerous impact of unsafe physical or
      sexual relationship. So the people of developing countries like Bangladesh are
      very vulnerable in the aspect of erosion of values and spreading different types
      of sexually transmitted diseases.

PMID- 28766191
TI  - Promoting Afterschool Quality and Positive Youth Development: Cluster Randomized
      Trial of the Pax Good Behavior Game.
AB  - This randomized trial tested a strategy originally developed for school settings,
      the Pax Good Behavior Game (PAX GBG), in the new context of afterschool programs.
      We examined this approach in afterschool since 70% of all juvenile crime occurs
      between the hours of 3-6 pm, making afterschool an important setting for
      prevention and promotion. Dual-career and working families need monitoring and
      supervision for their children in quality settings that are safe and
      appropriately structured. While substantial work has identified important
      features of afterschool programs, increasing attention is being given to how to
      foster quality. PAX GBG, with its focus on shared norms, cooperative teams,
      contingent activity rewards, and liberal praise, could potentially enhance not
      only appropriate structure and supportive relationships, but also youth self
      regulation, co-regulation, and socio-emotional development. This study examined
      the PAX GBG among 76 afterschool programs, serving 811 youth ages 5-12, who were
      diverse in race-ethnicity, socio-economic status, and geographic locale.
      Demographically matched pairs of afterschool programs were randomized to PAX GBG
      or treatment-as-usual. Independent observers conducted ratings of implementation
      fidelity and program quality across time; along with surveys of children's
      problem and prosocial behavior. Interaction effects were found using hierarchical
      linear models such that experimental programs evidencing higher implementation
      fidelity demonstrated better program quality than controls, (i.e., less
      harshness, increased appropriate structure, support, and engagement), as well as
      reduced child-reported hyperactivity and intent-to-treat effects on prosocial
      behavior. This study demonstrates that best practices fostered by PAX GBG and
      implemented with fidelity in afterschool result in higher quality contexts for
      positive youth development.

PMID- 28766193
TI  - Filovirus Research: How it Began.
AB  - The first reported filovirus outbreak occurred in August 1967, when laboratory
      workers in Marburg and Frankfurt, Germany, and Belgrade, Yugoslavia (now Serbia)
      became infected with an unknown highly pathogenic agent. The disease was
      characterized by high fever, malaise, rash, hemorrhagic and tetanic
      manifestations, and high lethality, amounting to 25%. The disease was introduced
      to Europe by grivets (Chlorocebus aethiops), which were used for biomedical
      research and vaccine production. The causative agent, Marburg virus, was isolated
      and identified by scientists of the University of Marburg, Germany in cooperation
      with specialists for viral electron microscopy at the Bernhard Nocht Institute in
      Hamburg, Germany. In this chapter, Dr. Slenczka, who was involved in the first
      isolation of Marburg virus in 1967, describes the desperate hunt of the causative
      agent of this first filovirus disease outbreak in the center of Europe, its
      successful isolation, the likely route of transmission from a monkey trading
      station to vaccine production facilities in Germany and Yugoslavia, and the
      consequences of this outbreak, including a shortage in the production of
      poliomyelitis vaccine In addition, this chapter provides insight into some of the
      peculiarities of filovirus infection, such as sexual virus transmission several
      months after recovery and the role of Ca2+-loss in Marburg virus pathogenesis,
      which were already observed during this first well-documented Marburg virus
      disease outbreak.

PMID- 28766192
TI  - Iron metabolism and drug resistance in cancer.
AB  - Iron is an essential inorganic element for various cellular events. It is
      directly associated with cell proliferation and growth; therefore, it is expected
      that iron metabolism is altered in tumor cells which usually have rapid growth
      rates. The studies on iron metabolism of tumor cells have shown that tumor cells
      necessitated higher concentrations of iron and the genes of iron uptake proteins
      were highly over-expressed. However, there are limited number of studies on
      overall iron metabolism in drug-resistant tumor cells. In this article, we
      evaluated the studies reporting the relationship between drug resistance and iron
      metabolism and the utilization of this knowledge for the reversal of drug
      resistance. Also, the studies on iron-related cell death mechanism, ferroptosis,
      and its relation to drug resistance were reviewed. We focus on the importance of
      iron metabolism in drug-resistant cancer cells and how alterations in iron
      metabolism participate in drug-resistant phenotype.

PMID- 28766194
TI  - MACRA and the Changing Medicare Payment Landscape.
AB  - BACKGROUND: The Medicare Access and CHIP Reauthorization Act (MACRA) is being
      implemented in 2017 by the Centers for Medicare and Medicaid Services (CMS) as
      the Quality Payment Program (QPP) and will have important and far reaching
      effects on how physicians are reimbursed and on how they practice. The QPP
      modifies the Medicare physician payment system by eliminating the Sustainable
      Growth Rate formula and incorporating the existing Physician Quality Reporting
      System, EHR Incentive Program, and the Value Modifier into a single new Merit
      based Incentive Payment System (MIPS). METHODS: The authors reviewed the MACRA
      legislation as well as the CMS resources on the QPP and other sources to
      summarize the regulations pertaining to the new program, particularly for the
      first performance period. RESULTS: CMS has taken great care to create a smooth
      transition for Medicare physicians. Clinicians can avoid any penalty for
      performance in 2017 by submitting a minimal amount of quality data, attesting to
      a single improvement activity, or successfully attaining the base score for the
      advancing care information portion of MIPS. The reduced reporting period also
      makes it possible for participants to begin collecting data as late as October
      2nd and still achieve the full possible score in the program. CONCLUSIONS:
      Surgeons should be taking steps now to ensure that they are prepared to succeed
      in the QPP. The transition period creates a clear pathway for avoiding penalties
      while providing an opportunity to test one's ability to participate and improve
      performance.

PMID- 28766195
TI  - Association of LN Evaluation with Survival in Women Aged 70 Years or Older With
      Clinically Node-Negative Hormone Receptor Positive Breast Cancer.
AB  - BACKGROUND: Some suggest that lymph node (LN) evaluation not be performed
      routinely in women aged >=70 years with clinically (c) LN-negative (-), hormone
      receptor (HR)-positive (+) breast cancer. We sought to determine the association
      of omission of LN evaluation on survival. METHODS: Patients who met the above
      criteria and were diagnosed from 2004 to 2012 were identified in the NCDB and
      SEER databases. Overall survival (OS) and breast cancer-specific survival (BCSS)
      were determined. RESULTS: Using the NCDB, we identified 157,584 cLN- HR+ patients
      aged >=70 years in whom survival and LN evaluation data were available. A total
      of 126,638 patients (80.2%) had regional LN surgery. With a median follow-up of
      41.6 months, there was a significant difference in OS between those who had LN
      evaluation and those who did not (median OS: 100.5 vs. 70.9 months, respectively,
      p < 0.001). After adjusting for patient age, race, insurance, income,
      comorbidities, tumor characteristics and treatment, patients who had undergone LN
      evaluation still had a lower hazard rate for death than those who had not (hazard
      ratio = 0.633; 95% confidence interval [CI] 0.613-0.654, p < 0.001). We then did
      a parallel analysis using SEER data that showed LN evaluation was associated with
      a lower hazard rate for both BCSS (hazard ratio = 0.452; 95% CI 0.427-0.479, p <
      0.001) and non-BCSS (hazard ratio = 0.465; 95% CI 0.447-0.482, p < 0.001).
      CONCLUSIONS: Roughly 20% of patients older than aged 70 years with cLN-, HR+
      breast cancer did not have LN evaluation. Those who did had better OS controlling
      for sociodemographic, pathologic, and treatment variables; however, this may be
      due to patient selection.

PMID- 28766196
TI  - A Validated Nomogram to Predict Upstaging of Ductal Carcinoma in Situ to Invasive
      Disease.
AB  - BACKGROUND: Approximately 8-56% of patients with a core needle biopsy (CNB)
      diagnosis of ductal carcinoma in situ (DCIS) will be upstaged to invasive disease
      at the time of excision. Patients with invasive disease are recommended to
      undergo axillary nodal staging, most often requiring a second operation. We
      developed and validated a nomogram to preoperatively predict percentage of risk
      for upstaging to invasive cancer. METHODS: We reviewed 834 cases of DCIS on CNB
      between January 2004 and October 2014. Multivariable analysis was used to
      evaluate CNB and imaging factors to develop a nomogram to predict the risk of
      upstaging from DCIS to invasive cancer. This nomogram was validated with an
      external dataset of 579 similar patients between November 1998 and September
      2016. An area under the receiver operating characteristic curve was constructed
      to evaluate nomogram discrimination. RESULTS: The rate of upstaging to invasive
      disease was 118/834 (14.1%). On multivariable analysis, grade on CNB and imaging
      factors, including mass lesion, multicentric disease, and largest linear
      dimension, were associated with upstage to invasive disease, and was used to
      develop a nomogram (c-statistic 0.71). In the external validation dataset, 62/579
      (10.7%) patients were upstaged to invasive disease. Our nomogram was validated in
      this dataset with a c-statistic of 0.71. CONCLUSION: For patients with a CNB
      diagnosis of DCIS, our validated nomogram using DCIS grade on biopsy, and imaging
      factors of mass lesion, multicentric disease, and largest linear dimension, may
      be used for preoperative assessment of risk of upstaging to invasive disease,
      allowing patient counseling regarding axillary staging at the time of definitive
      surgery.

PMID- 28766197
TI  - Predicting Nodal Positivity in Women 70 Years of Age and Older with Hormone
      Receptor-Positive Breast Cancer to Aid Incorporation of a Society of Surgical
      Oncology Choosing Wisely Guideline into Clinical Practice.
AB  - PURPOSE: One of the Society of Surgical Oncology Choosing Wisely guidelines
      recommends avoiding routine sentinel lymph node (SLN) surgery in clinically node
      negative women >=70 years of age with hormone receptor-positive (HR+) breast
      cancer. We sought to assess the impact of tumor stage and grade on nodal
      positivity, and to develop a model to identify patients at low-risk of nodal
      positivity to aid adoption of the guideline. METHODS: We identified women >=70
      years of age with HR+ cN0 invasive breast cancer in the National Cancer Database
      (NCDB; 2010-2013) and examined the impact of tumor stage and grade on nodal
      positivity to identify low-risk combinations. A multivariable logistic regression
      model was developed to incorporate additional factors. The area under the curve
      (AUC) and relative risks (RR) were used to assess performance. RESULTS: Among
      71,834 cases, the pathologic nodal positivity (pN+) rate was 15.3%. We identified
      low-risk criteria as grade 1, cT1mi-T1c (<=2.0 cm), or grade 2, cT1mi-T1b (<=1.0
      cm), with pN+ rates of 7.8% compared with 22.3% in patients not meeting these
      criteria (RR 2.86, p < 0.001). On multivariable analysis, factors associated with
      pN+ status included clinical T stage, grade, and histology (each p < 0.001). The
      resulting model had AUC 0.70 and identified women with low predicted probability
      (<10%) of positive nodes, of whom 6.3% were pN+, versus 21.2% in those with
      predicted probability >=10% (RR 3.34, p < 0.001). CONCLUSION: The simple clinical
      rule (grade 1, cT1mi-T1c, or grade 2, cT1mi-T1b), as well as the predictive
      model, both identify women at low risk of nodal positivity where SLN surgery can
      be omitted.

PMID- 28766198
TI  - Factors Influencing Management and Outcome in Patients with Occult Breast Cancer
      with Axillary Lymph Node Involvement: Analysis of the National Cancer Database.
AB  - BACKGROUND: Occult breast cancer (OBC) is rare and optimal local-regional (LR)
      management has not been defined. Using a patient registry database, we examine
      factors associated with treatment and outcomes in OBC. METHODS: Female patients
      with cT0 N1/2 M0 BC were selected from the National Cancer Database (2004-2013)
      and categorized into four treatment groups: MAST = mastectomy with axillary lymph
      node dissection (ALND) +/- radiation (RT); RT + ALND = RT with ALND, no breast
      surgery; ALND = ALND alone; OBS = no breast surgery, RT, or ALND. Patient
      characteristics and overall survival (OS) were compared between groups, and
      multivariable analysis was used to identify factors associated with treatment and
      OS. RESULTS: Among 2.03 million BC cases, 1853 females (0.09%) with cT0 N1/2 M0
      disease were identified and 1231 patients were categorized into a treatment
      group: MAST = 592, RT + ALND = 342, ALND = 106, OBS = 191. On logistic
      regression, care at an academic center was associated with a higher likelihood of
      RT + ALND compared with MAST (odds ratio 2.03, 95% confidence interval [CI] 1.50
      2.74, p < 0.001). Patients treated with RT + ALND had significantly better OS on
      univariate survival analysis compared with patients treated with MAST (hazard
      ratio [HR] 0.475, 95% CI 0.306-0.736, p = 0.001). RT + ALND was independently
      associated with OS on multivariable survival analysis (HR 0.509, 95% CI 0.321
      0.808, p = 0.004), after adjusting for covariates. CONCLUSIONS: Patients with OBC
      were more likely to undergo RT + ALND if they received care at an academic
      center. Patients treated with RT + ALND had significantly better OS compared with
      patients treated with MAST, after adjusting for covariates. This supports the use
      of RT + ALND as LR treatment for patients with OBC.

PMID- 28766199
TI  - A Patient-Specific 3D-Printed Form Accurately Transfers Supine MRI-Derived Tumor
      Localization Information to Guide Breast-Conserving Surgery.
AB  - BACKGROUND: Wire-localized excision of nonpalpable breast cancer is imprecise,
      resulting in positive margins 25-30% of the time. METHODS: Patients underwent
      preoperative supine magnetic resonance imaging (MRI). A radiologist outlined the
      tumor edges on consecutive images, creating a three-dimensional (3D) view of its
      location. Using 3D printing, a bra-like plastic form (the Breast Cancer Locator
      [BCL]) was fabricated, with features that allowed a surgeon to (1) mark the edges
      of the tumor on the breast surface; (2) inject blue dye into the breast 1 cm from
      the tumor edges; and (3) place a wire in the tumor at the time of surgery.
      RESULTS: Nineteen patients with palpable cancers underwent partial mastectomy
      after placement of surgical cues using patient-specific BCLs. The cues were in
      place in <5 min and no adverse events occurred. The BCL accurately localized
      18/19 cancers. In the 18 accurately localized cases, all 68 blue-dye injections
      were outside of the tumor edges. Median distance from the blue-dye center to the
      pathologic tumor edge was 1.4 cm, while distance from the blue dye to the tumor
      edge was <5 mm in 4% of injections, 0.5-2.0 cm in 72% of injections, and >2 cm in
      24% of injections. Median distance from the tumor center to the BCL-localized
      wire and to the clip placed at the time of diagnosis was similar (0.49 vs. 0.73
      cm) on specimen mammograms. CONCLUSIONS: Information on breast cancer location
      and shape derived from a supine MRI can be transferred safely and accurately to
      patients in the operating room using a 3D-printed form.

PMID- 28766200
TI  - Keynote Address at the American Society of Breast Surgeons 18th Annual Meeting :
      Current and Future Application of Intraoperative Radiotherapy (IORT) in the
      Curative and Palliative Treatment of Breast Cancer.
AB  - Intraoperative radiotherapy (IORT) is increasingly used worldwide. Breast cancer
      is the most rapidly growing indication for IORT, approaching 70-80% of cases in
      most centers. This report reviews the theoretical background and clinical use of
      IORT for primary and metastasized breast cancer. There are established
      applications such as tumor bed boost during breast-conserving surgery followed by
      whole breast radiotherapy or IORT as a form of accelerated partial-breast
      irradiation (APBI) for selected patients. Novel applications such as IORT for
      vertebral or brain metastases are presented as well as technological
      developments, widening the spectrum of potential clinical applications for IORT.

PMID- 28766201
TI  - Selective Use of Sentinel Lymph Node Surgery in Patients Undergoing Prophylactic
      Mastectomy Using Intraoperative Pathology.
AB  - BACKGROUND: Routine sentinel lymph node (SLN) surgery during prophylactic
      mastectomy (PM) is unnecessary, because most PMs do not contain cancer. Our
      institution utilizes intraoperative pathology to guide the surgical decision for
      resection of SLNs in PM. The purpose of this study was to review the
      effectiveness of this approach. METHODS: We identified all women aged >=18 years
      who underwent bilateral PM (BPM) or contralateral PM (CPM) at our institution
      from January 2008 to July 2016. We evaluated the frequency of SLN resection and
      rate of occult breast cancer (DCIS or invasive disease) in the PM. We used the
      following definitions: over-treatment-SLN surgery in patients without cancer;
      under-treatment-no SLN surgery in patients with cancer; appropriate treatment-no
      SLN in patients without cancer or SLN surgery in patients with cancer. RESULTS:
      PM was performed on 1900 breasts: 1410 (74.2%) CPMs and 490 (25.8%) BPMs. Cancer
      was identified in 58 (3.0%) cases (32 invasive disease and 26 DCIS) and
      concurrent SLN surgery was performed in 44 (75.9%) of those cases. Overall, SLN
      surgery guided by intraoperative pathology resulted in appropriate treatment of
      1787 (94.1%) cases: 1319 (93.5%) CPMs and 468 (95.5%) BPMs, by avoiding SLN in
      1743/1842 cases without cancer (94.6%), and performing SLN surgery in 44/58 cases
      with cancer (75.9%). CONCLUSIONS: Use of intraoperative pathology to direct SLN
      surgery in patients undergoing PM minimizes over-treatment from routine SLN in PM
      and minimizes under-treatment from avoiding SLN in PM, demonstrating the value of
      intraoperative pathology in this era of focus on appropriateness of care.

PMID- 28766202
TI  - Preoperative Panel Testing for Hereditary Cancer Syndromes Does Not Significantly
      Impact Time to Surgery for Newly Diagnosed Breast Cancer Patients Compared with
      BRCA1/2 Testing.
AB  - BACKGROUND: This study seeks to determine whether there is a delay in time to
      surgery in breast cancer patients with panel tests compared with traditional BRCA
      testing. METHODS: This study was a retrospective review of women diagnosed with
      breast cancer who underwent genetic evaluation from our institution's Genetic
      Counselor Database from January 2013 to August 2015. Patients were excluded if
      they were male, clinical information was unavailable, the patient underwent
      neoadjuvant chemotherapy, had a diagnosis of recurrent breast cancer during time
      of study, or had postoperative genetics evaluation. RESULTS: Included in the
      study were 138 patients. The time from diagnosis to surgery for BRCA1/2 tested
      patients was 43.5 days compared with 51.0 days in the panel group (p = 0.186).
      Turnaround time for genetic testing decreased during the period studied and was
      approximately 6 days longer for panel testing than BRCA testing. It took 12.2
      days for BRCA results and 18.9 days for the panel results (p < 0.01). Turnaround
      time for BRCA1/2 testing in 2014 and 2015 was 12.4 and 10.5 days respectively,
      whereas panel testing was 20.5 and 18.2 days (p <= 0.001). Of the variables
      included in multivariable linear regression, only mastectomy significantly
      contributed to time to surgery (p < 0.001). DISCUSSION: Panel genetic testing did
      not delay time to surgery compared with BRCA testing alone. The use of panel
      testing has increased over time, and lab turnaround time has decreased.
      Mastectomy was the only clinical variable contributing to longer time to surgery.

PMID- 28766203
TI  - Lobular Neoplasia and Atypical Ductal Hyperplasia on Core Biopsy: Current
      Surgical Management Recommendations.

PMID- 28766204
TI  - Nonoperative Management for Invasive Breast Cancer After Neoadjuvant Systemic
      Therapy: Conceptual Basis and Fundamental International Feasibility Clinical
      Trials.
AB  - With current advances in neoadjuvant systemic therapy (NST) and improved breast
      imaging, the potential of nonoperative therapy for invasive breast cancer has
      emerged as a viable option when utilizing meticulous image-guided percutaneous
      biopsy to document pathologic complete response. Feasibility clinical trials
      utilizing this approach are being performed by teams of investigators from single
      and multicenter/cooperative groups around the world. Imaging alone after NST
      lacks sufficient sensitivity and specificity in predicting pCR and therefore
      cannot be utilized for clinical selection of patients for omission of surgery.
      Imaging with adequate sampling after NST of the residual lesions (or around the
      remaining clip if a complete radiologic response occurs) appears to be essential
      in selecting patients with pCR to lower the false-negative rates based on initial
      reported feasibility studies to identify pCR without surgery that range from 5 to
      49%. In this manuscript, recently completed, ongoing, and planned clinical
      feasibility trials and a new omission of surgery trial are described. Drastic
      rethinking of all diagnostic and therapeutic management strategies that are
      ordinarily utilized for patients who receive standard breast cancer surgery is
      required. A roadmap of essential questions and issues that will have to be
      resolved as the field of nonoperative breast cancer management advances is
      described in detail.

PMID- 28766205
TI  - A Single Institution Retrospective Comparison Study of Locoregional Recurrence
      After Accelerated Partial Breast Irradiation Using External Beam Fractionation
      Compared with Whole Breast Irradiation with 8 Years of Follow-Up.
AB  - BACKGROUND: Accelerated partial breast irradiation (APBI) was developed to
      address disadvantages of overall treatment time and potentially unnecessary
      radiation associated with whole breast irradiation (WBI). We report updated
      results of our single institution study using an external beam APBI regimen with
      a median follow-up of 8 years. METHODS: A total of 290 APBI patients with AJCC
      Stage 0-II breast cancer were compared with 290 WBI patients with matched tumor
      characteristics. Toxicities were scored based on the Common Terminology Criteria
      for Adverse Events (CTCAE v3.0). Cox regression models were used to predict
      likelihood of freedom from ipsilateral failure. RESULTS: Median follow-up was 8
      years in the APBI group and 7.5 years in the WBI group. In the APBI group, there
      were 18 (6.2%) ipsilateral breast tumor recurrence (IBTR), 13 (72%) had elsewhere
      failures (EF), and 5 (28%) had local failures (LF) with a median time to failure
      of 64.1 months. In the WBI group, there were three (1.0%) IBTR; one (33%) was an
      EF and two (67%) were LF with a median time to failure of 91 months. APBI was 4.6
      times more likely (hazard ratio 4.57, 95% confidence interval 1.3-16.2, p = 0.02)
      to have an IBTR than WBI after adjusting for age, tumor size, histology, grade,
      and estrogen receptor status. Fatigue, erythema, and desquamation toxicities were
      significantly less in the APBI group then the WBI group. CONCLUSIONS: IBTR rates
      were higher in external beam APBI group compared with WBI, but APBI had fewer
      toxicities. Clinicians must weigh the risks and benefits of APBI when making a
      recommendation for partial breast irradiation after lumpectomy.

PMID- 28766206
TI  - The American Society of Breast Surgeons and Quality Payment Programs: Ranking,
      Defining, and Benchmarking More Than 1 Million Patient Quality Measure
      Encounters.
AB  - BACKGROUND: To identify and remediate gaps in the quality of surgical care, the
      American Society of Breast Surgeons (ASBrS) developed surgeon-specific quality
      measures (QMs), built a patient registry, and nominated itself to become a Center
      for Medicare and Medicaid Services (CMS) Qualified Clinical Data Registry (QCDR),
      thereby linking surgical performance to potential reimbursement and public
      reporting. This report provides a summary of the program development. METHODS:
      Using a modified Delphi process, more than 100 measures of care quality were
      ranked. In compliance with CMS rules, selected QMs were specified with inclusion,
      exclusion, and exception criteria, then incorporated into an electronic patient
      registry. After surgeons entered QM data into the registry, the ASBrS provided
      real-time peer performance comparisons. RESULTS: After ranking, 9 of 144 measures
      of quality were chosen, submitted, and subsequently accepted by CMS as a QCDR in
      2014. The measures selected were diagnosis of cancer by needle biopsy, surgical
      site infection, mastectomy reoperation rate, and appropriateness of specimen
      imaging, intraoperative specimen orientation, sentinel node use, hereditary
      assessment, antibiotic choice, and antibiotic duration. More than 1 million
      patient-measure encounters were captured from 2010 to 2015. Benchmarking
      functionality with peer performance comparison was successful. In 2016, the ASBrS
      provided public transparency on its website for the 2015 performance reported by
      our surgeon participants. CONCLUSIONS: In an effort to improve quality of care
      and to participate in CMS quality payment programs, the ASBrS defined QMs,
      tracked compliance, provided benchmarking, and reported breast-specific QMs to
      the public.

PMID- 28766207
TI  - Use of Sentinel Lymph Node Dissection After Neoadjuvant Chemotherapy in Patients
      with Node-Positive Breast Cancer at Diagnosis: Practice Patterns of American
      Society of Breast Surgeons Members.
AB  - BACKGROUND: The accuracy of sentinel lymph node dissection (SLND) in clinically
      node-positive patients who receive neoadjuvant chemotherapy has been investigated
      in clinical trials. This survey was designed to assess familiarity and impact of
      these trial findings into practice. METHODS: American Society of Breast Surgeons
      members were invited by e-mail to complete an anonymous online survey. A total of
      642 members responded (21% of 3090 eligible members). Results were summarized as
      proportions based on the number of responses to each question. RESULTS:
      Respondents indicated knowledge of the Z1071 (86%), SENTINA (57%), and SN-FNAC
      (39%) trials. The published false negative rates (FNR) of the trials were
      correctly reported by 53% (336/638) of respondents. Before the trials, 45%
      (285/636) offered SLND compared with 85% (543/638) after the trials. In the 556
      respondents who reported knowledge of at least one trial, 310 (56%) currently
      offer SLND to >50% of patients, 175 (31%) offer to <50%, and 70 (13%) routinely
      perform axillary lymph node dissection. Respondents who reported knowledge of the
      trials but did not change their practice to incorporate SLND (n = 67) cited
      concerns over lack of outcome data (64%), worries about FNR (42%), lack of
      resources (34%), or objections from radiation oncologists (25%), medical
      oncologists (18%), or other surgeons (8%). CONCLUSIONS: The publication of trials
      evaluating SLND in clinically node-positive patients has resulted in changes in
      practice. Concerns over the FNR and lack of outcome data limit incorporation of
      SLND into practice by some surgeons.

PMID- 28766208
TI  - Contralateral Breast Cancer Risk in Women with Ductal Carcinoma In Situ: Is it
      High Enough to Justify Bilateral Mastectomy?
AB  - BACKGROUND: Women with ductal carcinoma in situ (DCIS) are increasingly choosing
      bilateral mastectomy. We sought to quantify rates of contralateral breast cancer
      (CBC) and ipsilateral breast tumor recurrence (IBTR) after breast-conserving
      surgery (BCS) for DCIS, and to compare risk factors for CBC and IBTR. METHODS:
      From 1978 to 2011, DCIS patients undergoing BCS with a contralateral breast at
      risk were identified from a prospectively maintained database. The association of
      clinicopathologic and treatment factors with CBC and IBTR were evaluated using
      Kaplan-Meier analysis, multivariable Cox regression, and competing risk
      regression (CRR). RESULTS: Of 2759 patients identified, 151 developed CBC and 344
      developed IBTR. Five- and 10-year Kaplan-Meier CBC rates were 3.2 and 6.4%.
      Overall, 10-year IBTR rates were 2.5-fold higher than CBC rates, and, without
      radiation, 4-fold higher. On CRR, 5- and 10-year rates were 2.9 and 5.8% for CBC,
      and 7.8 and 14.5% for IBTR. CBC risk and invasive CBC risk were not significantly
      associated with age, family history, presentation, nuclear grade, year of
      surgery, or radiation. By multivariable Cox regression, endocrine therapy was
      associated with lower CBC risk (hazard ratio 0.57, p = 0.03). Ten-year risk of
      subsequent CBC in the subset of patients who developed IBTR was similar to the
      cohort as a whole (8.1 vs. 6.4%). CONCLUSIONS: CBC rates were low across all
      groups, including those who experienced IBTR. CBC was not associated with factors
      that increase IBTR risk. While factors associated with IBTR risk are important in
      decision making regarding management of the index DCIS, they are not an
      indication for contralateral prophylactic mastectomy.

PMID- 28766209
TI  - Socioeconomic Factors Associated with Post-Mastectomy Immediate Reconstruction in
      a Contemporary Cohort of Breast Cancer Survivors.
AB  - BACKGROUND: Post-mastectomy reconstruction is a critical component of high
      quality breast cancer care. Prior studies demonstrate socioeconomic disparity in
      receipt of reconstruction. Our objective was to evaluate trends in receipt of
      immediate reconstruction and examine socioeconomic factors associated with
      reconstruction in a contemporary cohort. METHODS: Using the National Cancer
      Database, we identified women <75 years of age with stage 0-1 breast cancer
      treated with mastectomy (n = 297,121). Trends in immediate reconstruction rates
      (2004-2013) for the overall cohort and stratified by socioeconomic factors were
      examined using Join-point regression analysis, and annual percentage change (APC)
      was calculated. We then restricted our sample to a contemporary cohort (2010
      2013, n = 145,577). Multivariable logistic regression identified socioeconomic
      factors associated with immediate reconstruction. Average adjusted predicted
      probabilities of receiving reconstruction were calculated. RESULTS: Immediate
      reconstruction rates increased from 27 to 48%. Although absolute rates of
      reconstruction for each stratification group increased, similar APCs across
      strata led to persistent gaps in receipt of reconstruction. On multivariable
      logistic regression using our contemporary cohort, race, income, education, and
      insurance type were all strongly associated with immediate reconstruction.
      Patients with the lowest predicted probability of receiving reconstruction were
      patients with Medicaid who lived in areas with the lowest rates of high-school
      graduation (Black 42.4% [95% CI 40.5-44.3], White 45.7% [95% CI 43.9-47.4]).
      CONCLUSIONS: Although reconstruction rates have increased dramatically over the
      past decade, lower rates persist for disadvantaged patients. Understanding how
      socioeconomic factors influence receipt of reconstruction, and identifying
      modifiable factors, are critical next steps towards identifying interventions to
      reduce disparities in breast cancer surgical care.

PMID- 28766210
TI  - Positive Ultrasound-guided Lymph Node Needle Biopsy in Breast Cancer may not
      Mandate Axillary Lymph Node Dissection.
AB  - BACKGROUND: The ACOSOG Z0011 (Z11) trial demonstrated that in patients with
      nonpalpable axillary lymph nodes (LN) and one to two positive sentinel LN (SLN),
      axillary LN dissection (ALND) is unnecessary.JAMA 305:569-575, [2011], Ann Surg
      264:413-42, [2016] The Z11 trial did not require preoperative axillary ultrasound
      (axUS). In many centers, preoperative axUS is part of the standard workup of a
      newly diagnosed breast cancer patient, but in light of the Z11 results, its role
      is now questioned. METHODS: We retrospectively analyzed newly diagnosed breast
      cancer patients at two institutions. Inclusion criteria were patients with (1) no
      palpable lymphadenopathy, (2) abnormal axUS, (3) axillary LN metastasis confirmed
      preoperatively by axUS-lymph node needle biopsy, (4) no neoadjuvant therapy, and
      (5) ALND. LN disease burden was dichotomized as N1 versus N2-3. We examined
      relationships between clinicopathologic factors, including axUS characteristics,
      and LN disease burden. RESULTS: Of 129 included cases, 67 had N1 disease (51.9%)
      and 62 had N2-3 disease (48.1%). Factors significantly associated with N1 disease
      were tumor size <=2 cm (p = 0.012), nonlobular histology (p = 0.013), and one
      suspicious LN on axUS (p = 0.008). For patients with both tumor size on imaging
      <=2 cm and one abnormal LN on axUS, only 27% had N2-3 disease (p = 0.007).
      CONCLUSIONS: More than half of patients without palpable adenopathy but with
      preoperative US-guided biopsy proven axillary LN metastases had N1 disease. For
      patients with both tumor size <=2 cm and only 1 abnormal LN on axUS, 73% had N1
      disease. This suggests that such patients, if they are otherwise analogous to Z11
      patients, may undergo attempt at SLNB.

PMID- 28766211
TI  - Intraoperative Radiation Using Low-Kilovoltage X-Rays for Early Breast Cancer: A
      Single Site Trial.
AB  - INTRODUCTION: Two prospective, randomized trials, TARGIT-A and ELIOT, have shown
      intraoperative radiation therapy (IORT) to be a safe alternative to whole breast
      radiation therapy following breast-conserving surgery for selected low-risk
      patients. However, minimal data are available about the clinical effectiveness of
      this modality of treatment using the Xoft(r) Axxent(r) Electronic Brachytherapy
      (eBx(r)) System(r). METHODS: A total of 201 patients with 204 early-stage breast
      cancers were enrolled in a prospective X-ray IORT trial from June 2010 to
      September 2013. All tumors were treated with breast-conserving surgery and IORT.
      Data were collected at 1 week, 1 month, 6 months, 1 year, and yearly thereafter.
      RESULTS: With a median follow-up of 50 months, there have been seven ipsilateral
      breast tumor events (IBTE), no regional or distant recurrences, and no breast
      cancer-related deaths. One IBTE was within the IORT field, four outside of the
      IORT field but within the same quadrant as the index cancer, and two were new
      biologically different cancers in different quadrants. Three events were in
      patients who deviated from the protocol criteria. Kaplan-Meier analysis projects
      that 2.9% of patients will recur locally at 4 years. CONCLUSIONS: Recurrence
      rates observed in this trial were comparable to those of the TARGIT-A and ELIOT
      trials as well as the retrospective TARGIT-R trial. The low complication rates
      previously reported by our group as well as the low recurrence rates reported in
      this study support the cautious use and continued study of IORT in selected women
      with low-risk breast cancer.

PMID- 28766212
TI  - Evaluating the Risk of Upstaging HER2-Positive DCIS to Invasive Breast Cancer.
AB  - BACKGROUND: Overexpression of human epidermal growth factor 2 (HER2) in invasive
      breast cancer (IBC) is an independent poor prognostic factor. However, the
      significance of HER2 overexpression in ductal carcinoma in situ (DCIS) is not
      well defined. The current study assessed the correlation of HER2+ DCIS with the
      rate of upstaging to IBC on the final pathology. METHODS: The study
      retrospectively analyzed patients with the diagnosis of DCIS on core needle
      biopsy (CNB) at the authors' institution from 2009 to 2016. Data were analyzed
      using two-sample t tests. Multivariate analysis was performed using logistic
      regression. RESULTS: The study found that HER2+ DCIS had significantly higher
      rates of upstaging to IBC than HER2- DCIS (odds ratio [OR] 1.89; p = 0.012). In
      addition, triple-positive disease was more than two times more likely to be
      upstaged (OR 2.5; p = 0.01), whereas patients with estrogen (ER)-positive,
      progesterone (PR)-positive, and HER2- diseases were half as likely to be upstaged
      (OR 0.5; p = 0.04). Upstaging did not differ for patients with triple-negative
      disease (OR 0.89; p = 0.8). Additionally, patients with HER2+ DCIS were
      significantly younger regardless of ER/PR status (p = 0.03). The overexpression
      of HER2 in patients with an initial diagnosis of DCIS on CNB were twice as likely
      to have IBC on the final pathology as those who did not. CONCLUSION: The results
      suggest that overexpression of HER2 may serve as a biomarker for risk
      stratification of patients with DCIS and may help to guide treatment strategies
      in the future. For institutions in which HER2 testing may be performed on DCIS,
      patients should be counseled appropriately about the risk of upgrade to IBC.

PMID- 28766213
TI  - Expanded Gene Panel Use for Women With Breast Cancer: Identification and
      Intervention Beyond Breast Cancer Risk.
AB  - BACKGROUND: Clinicians ordering multi-gene next-generation sequencing panels for
      hereditary breast cancer risk have a variety of test panel options. Many panels
      include lesser known breast cancer genes or genes associated with other cancers.
      The authors hypothesized that using broader gene panels increases the
      identification of clinically significant findings, some relevant and others
      incidental to the testing indication. They examined clinician ordering patterns
      and compared the yield of pathogenic or likely pathogenic (P/LP) variants in non
      BRCA genes of female breast cancer patients. METHODS: This study analyzed de
      identified personal and family histories in 1085 breast cancer cases with P/LP
      multi-gene panel findings in non-BRCA cancer genes and sorted them into three
      groups by the panel used for testing: group A (breast cancer genes only), group B
      (commonly assessed cancers: breast, gynecologic, and gastrointestinal), and group
      C (a more expanded set of tumors). The frequency of P/LP variants in genes with
      established management guidelines was compared and evaluated for consistency with
      personal and family histories. RESULTS: This study identified 1131 P/LP variants
      and compared variants in clinically actionable genes for breast and non-breast
      cancers. Overall, 91.5% of these variants were in genes with management
      guidelines. Nearly 12% were unrelated to personal or family history. CONCLUSION:
      Broader panels were used for 85.6% of our cohort (groups B and C). Although
      pathogenic variants in non-BRCA genes are reportedly rare, the study found that
      most were in clinically actionable genes. Expanded panel testing improved the
      identification of hereditary cancer risk. Small, breast-limited panels may miss
      clinically relevant findings in genes associated with other heritable cancers.

PMID- 28766214
TI  - Factors Influencing Use of Hormone Therapy for Ductal Carcinoma In Situ: A
      National Cancer Database Study.
AB  - BACKGROUND: Adjuvant hormonal therapy (HT) reduces breast cancer recurrence risk
      in estrogen receptor-positive (ER+) ductal carcinoma in situ (DCIS). We assessed
      national practice patterns and influence of surgery and pathology on HT use in
      DCIS. METHODS: Data on DCIS patients diagnosed from 2004 to 2014 were extracted
      from the National Cancer Database, and patients were classified according to ER
      status and whether HT was received. Factors associated with HT use were assessed
      using Chi square tests for univariate analysis and logistic regression for
      multivariate analysis. RESULTS: Overall, 207,738 patients were evaluable as
      follows: ER+ (69.3%), ER- (13.7%), and ER unknown (17.0%). Among ER+ DCIS
      patients, 46.5% received HT, and HT use increased over time (42.3% in 2004 to
      50.6% in 2014; p < 0.001). In contrast, 7.8% of ER- DCIS patients received HT,
      decreasing from 10.7% in 2004 to 5.9% in 2014 (p < 0.001). HT use varied by
      surgery type (BCS, 53.9%; unilateral mastectomy, 31.5%; and bilateral mastectomy,
      8.1%; p < 0.001) and use was higher in BCS patients receiving adjuvant radiation
      than those not receiving radiation (62.7 vs. 29.1%; p < 0.001). Males treated
      with BCS were less likely to receive HT than females (43.2 vs. 54.0%; p < 0.001).
      In the BCS subset, higher use of HT was associated with more recent calendar
      year, age between 40 and 80 years, female sex, positive progesterone receptor
      status, and radiation use. CONCLUSION: Adjuvant HT use in ER+ DCIS has increased
      over time, with the highest rates in patients treated with BCS and radiation.
      While inappropriate HT use was observed in ER- and bilateral mastectomy patients,
      the frequency of use in these categories decreased over time.

PMID- 28766215
TI  - The Androgen Receptor: Is It a Promising Target?
AB  - A growing body of literature supports the conclusion that the androgen receptor
      (AR) plays an important role in breast cancer pathogenesis and may prove to be a
      relevant therapeutic target for patients with AR-driven breast cancer. This has
      been most apparent in the subset of patients with triple-negative breast cancer
      (TNBC), in whom approximately 50% of tumors may have androgen dependence. Recent
      phase 2 clinical trials of agents that antagonize AR or reduce androgen
      production have shown clinical benefit and efficacy to varying degrees. This
      review highlights three of these recent trials of AR+ TNBC and acknowledge
      ongoing research in this exciting area.

PMID- 28766216
TI  - Challenging Atypical Breast Lesions Including Flat Epithelial Atypia, Radial
      Scar, and Intraductal Papilloma.

PMID- 28766217
TI  - The Influence of Breast Density on Preoperative MRI Findings and Outcome in
      Patients with a Known Diagnosis of Breast Cancer.
AB  - BACKGROUND: The role of breast density as an indication for preoperative breast
      magnetic resonance imaging (MRI) for surgical planning in women with breast
      cancer is unknown. METHODS: We retrospectively reviewed breast cancer patients
      diagnosed from 2007 to 2011 who underwent preoperative MRI. We obtained clinical
      and pathological data and grouped patients by mammographic breast density, with
      Breast Imaging Reporting and Data System (BI-RADS) density A and B considered low
      density, and C and D considered high density. We analyzed local recurrence rates
      by breast density. RESULTS: Among 683 patients, 66.6% had high breast density. We
      noted MRI abnormalities in the ipsilateral breast in 41.8% high-density and 30.7%
      low-density breasts, while contralateral abnormalities were noted in 24.9% high
      density and 13.8% low-density breasts. Biopsy was recommended for MRI findings in
      a similar number of patients regardless of density cohort. While more
      abnormalities were found in high-density breasts, the rate of additional cancer
      found was not significantly different (ipsilateral: 32 vs. 23%; contralateral:
      6.2 vs. 3.2%) for high-and low-density patients, respectively (both p > 0.15).
      With a median follow-up of 89 months, and similar rates of adjuvant systemic and
      radiation therapy, no difference in local recurrence rates existed when
      stratified according to density classification (p > 0.53). CONCLUSION: While more
      abnormalities were identified on MRI in dense breasts, there was no statistically
      significant difference in the number of cancers identified or in recurrence
      rates. These findings question the routine use of preoperative breast MRI in
      women with newly diagnosed breast cancer based solely on breast density.

PMID- 28766218
TI  - Considerations for Clinicians in the Diagnosis, Prevention, and Treatment of
      Breast Cancer-Related Lymphedema, Recommendations from an Expert Panel: Part 2:
      Preventive and Therapeutic Options.

PMID- 28766219
TI  - A 10-Year Experience with Mastectomy and Tissue Expander Placement to Facilitate
      Subsequent Radiation and Reconstruction.
AB  - BACKGROUND: An integrated approach to skin sparing mastectomy with tissue
      expander placement followed by radiotherapy and delayed reconstruction was
      initiated in our institution in 2002. The purpose of this study was to assess the
      surgical outcomes of this strategy. METHODS: Between September 2002 and August
      2013, a total of 384 reconstructions had a tissue expander placed at the time of
      mastectomy and subsequently underwent radiotherapy. Rates and causes of tissue
      expander explantation before, during, and after radiotherapy, as well as tumor
      specific outcomes and reconstruction approaches, were collected. RESULTS: Median
      follow-up after diagnosis was 5.6 (range 1.3-13.4) years. In the study cohort,
      364 patients (94.8%) had stage II-III breast cancer, and 7 patients (1.8%) had
      locally recurrent disease. The 5-year rates of actuarial locoregional control,
      disease-free survival, and overall survival were 99.2, 86.1, and 92.4%,
      respectively. The intended delayed-immediate reconstruction was subsequently
      completed in 325 of 384 mastectomies (84.6% of the study cohort). Of the
      remaining 59 tissue expanders, 1 was explanted before radiotherapy, 1 during
      radiotherapy, and 7 patients (1.8%) were lost to follow-up. Fifty patients
      (13.0%) required tissue expander explantation after radiation and before their
      planned final reconstruction, primarily due to cellulitis. Nonetheless, the
      cumulative rate of completed reconstructions was 89.6%. The median time from
      placement of the tissue expander until reconstruction was 12 (interquartile range
      9-15) months. CONCLUSIONS: Tissue expander placement at skin-sparing mastectomy
      in patients who require radiotherapy appears to be a viable strategy for
      combining reconstruction and radiotherapy.

PMID- 28766220
TI  - Improved Locoregional Control in a Contemporary Cohort of Nonmetastatic
      Inflammatory Breast Cancer Patients Undergoing Surgery.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive form of breast
      cancer characterized by rapid progression and early metastatic dissemination. The
      purpose of this study was to assess contemporary rates of local regional
      recurrence (LRR) in the era of trimodality therapy for nonmetastatic IBC and
      identify risk factors leading to local failure. METHODS: A total of 114 patients
      with nonmetastatic IBC receiving trimodality therapy (neoadjuvant chemotherapy,
      surgery, and radiation therapy) were identified from a prospectively collected
      database from 2007 to 2015 and outcomes analyzed. RESULTS: Median age at
      diagnosis was 52 years, and the median follow-up was 3.6 years. Sixty-three (55%)
      patients presented with N2 IBC, and 52 patients (45%) presented with N3 IBC.
      Local regional recurrence was observed during follow-up for four patients; 25
      died, and 85 were censored at last follow-up. Surgical margins were negative in
      99% of patients (n = 113). The 2-year probability of LRR was 3.19% (95%
      confidence interval 1.03-9.90%). Five-year overall survival for this cohort was
      69.14%. Improvement in disease-free survival was seen among patients with HER2+
      subtype, clinical stage IIIB, complete or partial radiologic response to
      neoadjuvant therapy, pathologic complete response, and lower nodal burden on
      presentation. CONCLUSIONS: Locoregional recurrences were rare at a median of 3.6
      years follow-up in a contemporary cohort of IBC patients treated with trimodality
      therapy. Although longer follow-up is needed, aggressive surgical resection to
      negative margins in the frame of trimodality therapy with curative intent can
      lead to LRR rates that mirror non-IBC rates.

PMID- 28766221
TI  - Association Between Recurrence and Re-Excision for Close and Positive Margins
      Versus Observation in Patients with Benign Phyllodes Tumors.
AB  - BACKGROUND: Breast lesions not sampled prior to surgery or initially diagnosed as
      fibroepithelial lesions on core biopsy may have a diagnosis of phyllodes tumor
      (PT) on excision. Historically, re-excision for close or positive margins has
      been the standard of care. We examined the rate of re-excision for close or
      positive margins in patients with benign phyllodes and compared recurrence rates
      among those undergoing re-excision versus observation. METHODS: We identified all
      patients with phyllodes tumor diagnosed between 2003 and 2013. Operative and
      surgical pathology reports were reviewed for clinical, pathologic, and follow-up
      data. RESULTS: Among 246 cases, 216 (88%) were benign PT and 30 (12%)
      borderline/malignant tumors. In the group of benign PT (n = 216), margins were
      negative in 64 patients (29.6%), 50 (23%) were close, and 102 (47%) were
      positive. Of those with close margins, 22 (44%) underwent reexcision and residual
      benign PT was found in 2 (9%). In patients with positive margins, 45 (44%) had re
      excision and residual benign PT was detected in 4 (8.8%). After a median follow
      up of 35.5 months, there were 4 (1.9%) recurrences among patients with benign PT.
      There was no difference in recurrence among patients who had re-excision for
      positive or close margins versus observation (p = 0.7 and 0.21, respectively).
      CONCLUSIONS: Among patients with close or positive margins, there was no
      significant difference in disease recurrence between patients who underwent
      reexcision and those who were observed. Based on these results, it may be
      reasonable to manage these patients conservatively with close follow-up.

PMID- 28766222
TI  - Breast Cancer Disparities: Socioeconomic Factors versus Biology.
AB  - Disparities in poverty and health care access barriers have a negative impact on
      the health and wellness of population subsets that bear a disproportionate share
      of these socioeconomic disadvantages, such as African Americans and
      Hispanic/Latina Americans. The more advanced stage distribution of breast cancer
      in these two population subsets is likely related to imbalance in distribution of
      socioeconomic resources in the United States. However, differences in the breast
      cancer burden of population subsets defined by racial/ethnic identity are also
      influenced by race/ethnicity-associated variation in tumor biology and hereditary
      susceptibility. Compared with white Americans, African-American women have higher
      population-based breast cancer mortality rates, which are at least partly
      explained by an increased risk for the biologically aggressive triple-negative
      phenotype. International studies correlate West African ancestry with
      predisposition for triple-negative breast cancer. In contrast, Hispanic/Latina
      Americans have lower population-based incidence and mortality rates for breast
      cancer despite their increased rates of socioeconomic challenges. Genetic studies
      suggest that extent of Native American ancestry among Hispanic/Latina women may
      reduce breast cancer risk. Eradication of disparate access to breast cancer early
      detection and treatment strategies is a public health imperative, but research to
      elucidate the genetics of breast cancer related to racial/ethnic identity is
      equally important as we strive to comprehensively define this complex disease.

PMID- 28766223
TI  - Differences Among a Modern Cohort of BRCA Mutation Carriers Choosing Bilateral
      Prophylactic Mastectomies Compared to Breast Surveillance.
AB  - BACKGROUND: Women with a BRCA mutation have significantly elevated breast cancer
      risk, which can be reduced by >90% with bilateral prophylactic mastectomy (BPM).
      We sought to compare a cohort of BRCA mutation carriers choosing BPM versus
      breast surveillance to better elucidate factors that may impact decision making.
      METHODS: Women with a BRCA mutation were retrospectively identified from a
      prospectively maintained database. The surveillance cohort (n = 313) consisted of
      women seen in a high-risk clinic between 2014 and 2016, while the surgery cohort
      (n = 142) consisted of women who underwent BPM between 2010 and 2016. Clinical
      and familial factors were compared between the groups. RESULTS: Women choosing
      BPM were more likely to have a BRCA1 than BRCA2 mutation compared with the
      surveillance group (57 vs. 45%, p = 0.02) and were less likely to have a personal
      history of ovarian cancer (10 vs. 20%, p = 0.01). Furthermore, women undergoing
      BPM were more likely to be married (78 vs. 62%, p = 0.01), to have more children
      (median 2 vs. 1, p < 0.001), and to have undergone a prophylactic oophorectomy
      (61 vs. 37%, p < 0.001). Women choosing BPM had more first-degree relatives (63
      vs. 48%, p = 0.01) or a sister (23 vs. 14%, p = 0.02) with a history of breast
      cancer and were more likely to have a family member with ovarian cancer under the
      age of 40 years (9 vs. 4%, p = 0.03). There was no difference in the number of
      prior breast biopsies or history of atypia/lobular carcinoma in situ. CONCLUSION:
      The decision to undergo BPM appears multifactorial, with gene mutation, family
      history, and relationships appearing to have the strongest influence on decision
      making.

PMID- 28766224
TI  - Clinical Decision-Making in Patients with Variant of Uncertain Significance in
      BRCA1 or BRCA2 Genes.
AB  - BACKGROUND: How diagnosis with a variant of uncertain significance (VUS) in a
      BRCA gene impacts clinical decision-making is not well known. METHODS: We queried
      for all patients attending Mayo Clinic Rochester from 2004 to 2016 who tested
      positive for BRCA1 or BRCA2 VUS and reviewed patient management choices. Groups
      were compared by using Wilcoxon rank-sum and Chi-square tests. RESULTS: We
      identified 97 patients (95 females, 2 males) with BRCA VUS. For patients without
      cancer history (n = 20), 80% had a mother or sister with breast cancer, and
      median Tyrer-Cuzick (IBIS) lifetime breast cancer risk score was 27% (range 16
      62%). Management included bilateral prophylactic mastectomy (BPM) in 39%, where
      choice for BPM was significantly associated with IBIS score (median 32 vs. 24%, p
      = 0.02) and first-degree family history of breast cancer (100 vs. 64%, p = 0.03)
      but not Gail score or total number of family members with cancer. For patients
      with breast cancer who had known VUS status prior to surgery (n = 9), the rate of
      contralateral prophylactic mastectomy (CPM) was 22% compared with 25% without
      known VUS and 83% with known BRCA pathogenic mutation. In 21 of 97 (22%)
      patients, the BRCA VUS has been reclassified (95% benign, 5% deleterious).
      CONCLUSIONS: BRCA VUS carriers with cancer elected surgical choices similar to
      average-risk breast cancer patients. However, VUS carriers without cancer had
      high rates of BPM, associated with first-degree family history and IBIS score.
      Over time, a significant proportion of BRCA VUS were reclassified, illustrating
      the importance of appropriate counseling regarding VUS.

PMID- 28766225
TI  - Influence of Distance to Hospital and Insurance Status on the Rates of
      Contralateral Prophylactic Mastectomy, a National Cancer Data Base study.
AB  - INTRODUCTION: We evaluated the impact of travel distance and insurance status on
      contralateral prophylactic mastectomy (CPM) rates in breast cancer. METHODS: We
      queried the National Cancer Data Base (NCDB) for women >18 years of age with a
      nonmetastatic primary breast cancer of ductal, lobular, or mixed histology.
      Patient- and facility-specific CPM rates were calculated based on insurance,
      race, and distance to treatment center. Standard univariable and multivariable
      regression analysis was performed. RESULTS: Overall, the CPM rate was 6.5% for
      the 864,105 patients identified. Most patients traveled <20 miles to a treatment
      center (79.5%) and had private insurance or Medicare (58.3 and 33.4%,
      respectively). In general, younger, White, non-Hispanic, and privately insured
      patients residing further from a treatment center was associated with increased
      rates of CPM. However, distance to the treatment center and insurance type had a
      greater absolute impact on rates of CPM for Black and Hispanic patients. Absolute
      CPM rate increases for patients >100 miles from a treatment center compared with
      those <20 miles from a treatment center were observed to be greater for Black and
      Hispanic patients (3.5 and 3.9%, respectively) compared with White and non
      Hispanic patients (2.5 and 2.6%). Additionally, further patient travel distance
      was associated with higher treatment center-specific CPM rates. CONCLUSION:
      Increased travel distance is independently associated with increased rates of CPM
      for all patients and increased facility-specific rates of CPM. Black and Hispanic
      patients were found to be more vulnerable to the impact of travel distance and
      insurance status on rates of CPM.

PMID- 28766226
TI  - Nipple-Sparing Mastectomy: Pitfalls and Challenges.

PMID- 28766227
TI  - Changing Dogma and Decreased Collateral Damage in Breast Cancer Care.

PMID- 28766229
TI  - Presidential Address: The Road Ahead-Challenges and Opportunities.

PMID- 28766228
TI  - Breast Cancer-Related Lymphedema Risk is Related to Multidisciplinary Treatment
      and Not Surgery Alone: Results from a Large Cohort Study.
AB  - BACKGROUND: Breast cancer-related lymphedema (BCRL) is a significant complication
      for women undergoing treatment. We assessed BCRL incidence and risk factors in a
      large population-based cohort. METHODS: We utilized the Olmsted County Rochester
      Epidemiology Project Breast Cancer Cohort from 1990-2010 and ascertained BCRL and
      risk factors. The cumulative incidence estimator was used to estimate the rate of
      BCRL; competing risks regression was used for multivariable analysis. RESULTS: A
      total of 1794 patients with stage 0-3 breast cancer with a median of 10 years
      follow-up were included. The cumulative incidence of BCRL diagnosis within 5
      years was 9.1% [95% confidence interval (CI) 7.8-10.5%]. No BCRL events occurred
      among patients without axillary surgery. In the axillary surgery subset (n =
      1512), the 5-year incidence of BCRL was 5.3% in sentinel lymph node (SLN) surgery
      and 15.9% in axillary dissection (ALND) patients (p < 0.001). In patients treated
      with surgery only, BCRL rates were not different between ALND versus SLN (3.5 and
      4.1% at 5 years, p = 0.36). Addition of breast or chest wall radiation more than
      doubled the BCRL rate in ALND patients (3.5 vs. 9.5% at 5 years, p = 0.01). The
      groups with highest risk (>25% at 5 years) all involved ALND with nodal RT and/or
      anthracycline/cytoxan + taxane chemotherapy. In multivariable analysis of
      patients with any axillary surgery factors significantly associated with BCRL
      were ALND, chemotherapy, radiation, and obesity. CONCLUSIONS: BCRL is a sequelae
      of multimodal breast cancer treatment and risk is multifactorial. BCRL rates are
      higher in patients receiving chemotherapy, radiation, ALND, more advanced disease
      stage, and higher body mass index.

PMID- 28766230
TI  - Clinical Relevance of microRNA Expressions in Breast Cancer Validated Using the
      Cancer Genome Atlas (TCGA).
AB  - BACKGROUND: MicroRNAs (miRNAs) play a critical role in the carcinogenesis and
      progression of breast cancer. MiRNA-205 has tumor suppressive properties, whereas
      miRNA-18a has both oncogenic and tumor suppressive roles. MiRNA-744's role in
      breast cancer is unknown but is tumor-suppressive in vitro. We hypothesize that
      high expression of all three miRNAs is associated with a better survival based on
      their known functions in breast cancer. METHODS: All data was obtained from the
      Cancer Genome Atlas (TCGA). Expression patterns of miRNA-18a, miRNA-205, and
      miRNA-744 were retrieved from the Genomic Data Commons (GDC) data portal for
      analyses. After miRNA-specific thresholds were derived and used to group the
      patients into a high- or low-expression group, survival data was calculated by
      using the Cox proportional hazard model. Further subanalyses separating the
      patients based on receptor status and AJCC 7th edition TNM staging were similarly
      compared. RESULTS: In total, 1,052 of 1,097 samples logged in TCGA had clinical
      data and miRNA-sequence datasets on the miRNAs of interest. High expression of
      miRNA-18a (p = 0.079), miRNA-205 (p = 0.034), and miRNA-744 (p = 0.0135) was
      associated with better survival. On subanalysis, estrogen receptor (ER)-positive,
      progesterone receptor (PR)-positive, and lymph node-negative disease had a
      statistically significant survival advantage with miRNA-18a, miRNA-205, and miRNA
      744 high expression. CONCLUSIONS: By utilizing a big dataset (TCGA) with
      sufficient statistical power, we found that high expression of miRNA-18a, miRNA
      205, and miRNA-744 in the breast tumor samples were all associated with better
      overall survival in ER/PR-positive, lymph node-negative disease supporting their
      role as a tumor suppressor in breast cancer.

PMID- 28766231
TI  - Contralateral Prophylactic Mastectomy with Immediate Breast Reconstruction
      Increases Healthcare Utilization and Cost.
AB  - BACKGROUND: The rates of contralateral prophylactic mastectomy (CPM) in women
      with unilateral breast cancer continue to rise, especially in women undergoing
      immediate breast reconstruction (IBR). METHODS: We utilized administrative claims
      data from a large US commercial insurance database (OptumLabs) to identify women
      age 18-64 years who underwent IBR between January 2004 and December 2013. We
      compared 2-year unadjusted utilization rates and total costs of care between
      unilateral mastectomy (UM) and bilateral mastectomy (BM) for implant-based and
      autologous reconstruction. Comparisons were tested using t-test and differences
      in cost were estimated using the Wilcoxon rank-sum test. RESULTS: Overall, 11,235
      women undergoing mastectomy with IBR were identified; 7319 with implant
      reconstruction [1923 UM (26%) and 5396 BM (74%)] and 3916 with autologous
      reconstruction [1687 UM (43%) and 2229 BM (57%)]. The overall rate of office
      visits (2386 vs. 2391 per 100 women, p = 0.42) and hospital readmission rate
      (29.1 per 100 women vs. 27.4, p = 0.06) were similar between BM + IBR and UM +
      IBR. Women undergoing BM + IBR had a higher emergency room (ER) visit rate (34.1
      per 100 women vs. 29.8, p < 0.0001). The total 2-year cost of care was higher for
      BM + IBR than UM + IBR for implant reconstruction ($106,711 vs. $97,218, p <
      0.0001) and for autologous reconstruction ($114,725 vs. $87,874, p < 0.0001).
      CONCLUSIONS: BM + IBR (autologous or implant) was associated with increased ER
      visits and higher total cost of care over 2 years compared with UM + IBR.
      Patients considering CPM should be counseled on the additional risks and costs
      associated with BM + IBR.

PMID- 28766232
TI  - Considerations for Clinicians in the Diagnosis, Prevention, and Treatment of
      Breast Cancer-Related Lymphedema: Recommendations from a Multidisciplinary Expert
      ASBrS Panel : Part 1: Definitions, Assessments, Education, and Future Directions.

PMID- 28766233
TI  - Prospective Study Comparing Surgeons' Pain and Fatigue Associated with Nipple
      Sparing versus Skin-Sparing Mastectomy.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) is more technically challenging than
      skin-sparing mastectomy (SSM) but offers quality-of-life and cosmetic advantages.
      However, surgeon physical symptoms related to NSM workload have not been
      documented. METHODS: This was a prospective study using questionnaires to compare
      surgeon-reported physical symptoms before, during, and after NSM versus SSM.
      Surgeons also answered general questions about each mastectomy. Bilateral cases
      were performed simultaneously by two surgeons, who completed independent
      questionnaires. RESULTS: Questionnaires were completed after 82 SSMs and 44 NSMs.
      On a 0-10 scale, surgeons reported NSM was more physically demanding than SSM
      (7.0 vs. 4.5, p < 0.001). Mean visualization was more difficult (5.7 vs. 3.2, p <
      0.001) and mean fatigue score was greater (5.6 vs. 3.1, p < 0.001) after NSM than
      SSM. The mean increase in neck pain (on a 0-4 scale) was greater for NSM than
      SSM, both from before-to-during surgery (0.8 vs. 0.2, p = 0.003) and before-to
      after surgery (0.9 vs. 0.2, p = 0.002). The mean increase in lower back pain was
      greater for NSM than SSM, both from before-to-during surgery (0.7 vs. 0.2, p =
      0.008) and before-to-after surgery (0.9 vs. 0.2, p = 0.003). Surgeons reported
      that NSM was more mentally demanding (p < 0.001), complex (p = 0.01), and
      difficult (p < 0.001) than SSM. CONCLUSION: Surgeons experienced greater physical
      symptoms, mental strain, and fatigue with NSM than SSM. This raises concern that
      mild but repetitive pain over the course of a breast surgeon's career may lead to
      repetitive stress injury.

PMID- 28766234
TI  - Localizing the Clipped Node in Patients with Node-Positive Breast Cancer Treated
      with Neoadjuvant Chemotherapy: Early Learning Experience and Challenges.
AB  - BACKGROUND: Placement of a clip in the positive node in patients presenting with
      node-positive breast cancer treated with neoadjuvant chemotherapy (NAC) allows
      resection of the clipped node at SLN surgery and improves the accuracy of
      surgical staging. We sought to evaluate our experience with SLN surgery with
      resection of the clipped node since incorporation into our practice. METHODS:
      With Institutional Review Board approval, we evaluated all breast cancer patients
      with a percutaneous biopsy-positive axillary lymph node, clipped at the time of
      diagnosis, who underwent NAC followed by surgery. RESULTS: Fifty-six node
      positive patients were identified. Eighteen patients (32.1%) underwent axillary
      dissection without sentinel lymph node (SLN) surgery, and 38 patients underwent
      SLN surgery (18 patients underwent SLN surgery alone, and 20 patients underwent
      SLN surgery and axillary lymph node dissection). In 25 patients, preoperative
      localization of the clipped node with an 125I radioactive seed was attempted.
      This was performed by ultrasound guidance in 18 cases (72%), computed tomography
      (CT) guidance in two cases (8%), and was unable to be localized in five cases
      (20%). In all 20 seed-localized cases, the seed and the clipped node were
      resected along with additional SLNs. In 14 patients without seed localization
      (nine not attempted, five unable to be localized), the clipped node was resected
      in 11 cases (79%)-as one of the SLNs (6), by intraoperative ultrasound (4), or by
      palpation (1). Overall, the clipped node was resected in 31/34 (91%) cases.
      CONCLUSION: Preoperative ultrasound localization of the clipped node was
      successful in 72% of cases. Alternatively, the clipped node can be identified by
      preoperative CT, routine SLN surgery, intraoperative ultrasound, or palpation.

PMID- 28766235
TI  - Polymorphisms in Epithelial-Mesenchymal Transition-Related Genes and the
      Prognosis of Surgically Treated Non-small Cell Lung Cancer.
AB  - BACKGROUND: This study was conducted to determine whether single-nucleotide
      polymorphisms (SNPs) in EMT-related genes may influence the prognosis of NSCLC
      after surgery. METHODS: There were 88 SNPs in EMT-related genes evaluated in a
      discovery set of 376 patients who underwent curative surgery for NSCLC.
      Significantly, 14 SNPs were evaluated in a validation set of 428 patients.
      Luciferase assay and RT-PCR were conducted to examine functional relevance of
      polymorphisms. RESULTS: Fourteen SNPs that were associated with survival outcomes
      in a discovery set were selected for validation. Among those, two SNPs (FOXF2
      rs1711972A>C and HEYL rs784621G>A) were replicated in a validation study. In
      combined analysis, FOXF2 rs1711972 AC+CC genotype was associated with
      significantly better overall survival (OS) and disease-free survival (DFS)
      compared with AA genotype (adjusted hazard ratio [aHR] for OS = 0.67, 95%
      confidence interval [CI] 0.51-0.88, P = 0.004; and aHR for DFS = 0.77, 95% CI
      0.62-0.95, P = 0.01). HEYL rs784621 AA genotype exhibited a significantly worse
      OS compared with GG+GA genotype (aHR for OS = 2.65, 95% CI 1.63-4.31, P = 8 * 10
      5). FOXF2 rs1711972C allele had a significantly increased promoter activity than
      rs1711972A allele (P = 0.01), and HEYL rs784621A allele had a significantly lower
      promoter activity than rs784621G allele (P = 0.004). FOXF2 rs1711972A>C was
      significantly associated with increased FOXF2 mRNA expression. CONCLUSIONS: FOXF2
      rs1711972A>C and HEYL rs784621G>A were associated with survival outcomes of
      surgically treated NSCLC. These SNPs may help to identify patients at high risk
      of poor disease outcomes.

PMID- 28766236
TI  - The impact of onabotulinumtoxinA on severe headache days: PREEMPT 56-week pooled
      analysis.
AB  - BACKGROUND: OnabotulinumtoxinA has been shown to reduce headache-days among
      patients with chronic migraine (CM). The objective of this analysis was to
      determine whether onabotulinumtoxinA has an impact on headache-day severity in
      patients with CM among those patients who were deemed non-responders based on
      reduction in the frequency of headache days alone. METHODS: Data from the Phase 3
      REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trial program
      (a 24-week, 2-treatment cycle, double-blind, randomized, placebo-controlled,
      parallel-group phase, followed by a 32-week, 3-treatment cycle, open-label phase)
      were pooled for analysis. Patients kept a daily diary to record headache severity
      on a 4-point scale (from none to severe), and a 6-domain Headache Impact Test
      (HIT-6) was used to determine the clinical impact of headaches. Analysis was
      undertaken to assess whether the subset of patients that were headache-day
      frequency non-responders at week 24 (patients with <50% reduction in headache-day
      frequency) experienced a reduction in headache severity whilst receiving
      onabotulinumtoxinA. RESULTS: For headache-day frequency non-responders,
      significant reductions in the number of severe headache days, average daily
      headache severity, pooled percentage of severe headache days and headache
      severity score were observed at week 24 for patients who had received
      onabotulinumtoxinA compared with those who had received placebo. The between
      group differences were reduced and non-significant at week 56. Similarly,
      headache-day frequency non-responders receiving onabotulinumtoxinA were found to
      have an improvement in the clinical impact of headaches using results from the
      HIT-6. CONCLUSIONS: These results suggest that even those patients with CM who
      are deemed non-responders based on analysis of headache frequency alone
      experience clinically meaningful relief from headache intensity following
      treatment with onabotulinumtoxinA.

PMID- 28766238
TI  - Magnesium isoglycyrrhizinate inhibits L-type Ca2+ channels, Ca2+ transients, and
      contractility but not hERG K+ channels.
AB  - To explore the cardiovascular protective effects of Magnesium isoglycyrrhizinate
      (MI), especially the underlying cellular mechanisms related to L-type calcium
      channels and myocardial contractility, and to examine the effects of MI on hERG
      K+ current expressed in HEK293 cells. We used the whole-cell patch clamp
      technique, video-based edge detection and dual excitation fluorescence
      photomultiplier systems to explore the effect of MI on L-type Ca2+ currents (ICa
      L) and cell contraction in rat cardiomyocytes. We also examined the rapidly
      activating delayed rectifier potassium current (IKr) expressed in HEK293 cells
      using a perforated patch clamp. MI inhibited ICa-L in a dose-dependent manner,
      with a half-maximal inhibitory concentration (IC50) of 0.22 mg/ml, and the
      maximal inhibitory effect was 61.10 +/- 0.59%. MI at a concentration of 0.3 mg/ml
      reduced cell shortening by 24.12 +/- 3.97% and the peak value of the Ca2+
      transient by 36.54 +/- 4.96%. MI had no significant influence on hERG K+ channels
      expressed in HEK293 cells at all test potentials. MI exerts protective effects on
      the heart via the inhibition of ICa-L and cell shortening in rat cardiomyocytes.
      However, MI had no significant influence on IKr; thus, MI may exert
      cardioprotective effects without causing drug-induced long QT syndrome.

PMID- 28766239
TI  - Transcriptome modeling and phenotypic assays for cancer precision medicine.
AB  - Cancer precision medicine requires clinically actionable biomarkers for patient
      stratification and a better prediction of clinical outcome. Although thousands of
      cancer-enriched mutated genes have been reported by global sequencing projects,
      to date, only a few oncogenic mutations have been confirmed as effective
      biomarkers in cancer therapies. The low frequency and varied profile (i.e.,
      allele frequency, mutation position) of mutant genes among cancer types limit the
      utility of predictive biomarkers. The recent explosion of cancer transcriptome
      and phenotypic screening data provides another opportunity for finding transcript
      level biomarkers and targets, thus overcoming the limitation of cancer mutation
      analyses. Technological developments enable the rapid and extensive discovery of
      potential target-biomarker combinations from large-scale transcriptome-level
      screening combined with physiologically relevant phenotypic assays. Here, we
      summarized recent progress as well as discussed the outlook of transcriptome
      oriented data mining strategies and phenotypic assays for the identification of
      non-genetic biomarkers and targets in cancer drug discovery.

PMID- 28766240
TI  - Determination of S-(-)-lansoprazole in dexlansoprazole preparation by capillary
      zone electrophoresis.
AB  - Capillary zone electrophoresis was successfully applied to the enantiomeric
      purity determination of dexlansoprazole using sulfobutyl ether-beta-cyclodextrin
      and methyl-beta-cyclodextrin as chiral selectors. Separations were carried out in
      a 50 MUm, 64/56 cm fused-silica capillary. The optimized conditions included 90
      mM phosphate buffer, pH 6.0, containing 30 mM sulfobutyl ether-beta-cyclodextrin,
      20 mM methyl-beta-cyclodextrin as background electrolyte, an applied voltage of
      25 kV and a temperature of 16  degrees C, detection was at 280 nm. The assay was
      validated for the S-(-)-lansoprazole in the range of 0.2-1.0%. The limit of
      detection was 0.07%, the limit of quantitation was 0.20%, relative to a total
      concentration of 4.0 mg mL-1. Intra-day precision varied between 1.72 and 2.07%.
      Relative standard deviations of inter-day precision ranged between 1.62 and 1.96%
      for peak area ratio. The assay was applied for the determination of the chiral
      purity of dexlansoprazole capsules. Recovery in capsules was ranged between 101.7
      and 103.1%.

PMID- 28766237
TI  - The Toxicology Investigators Consortium Case Registry-the 2016 Experience.
AB  - The Toxicology Investigators Consortium (ToxIC) Case Registry was established by
      the American College of Medical Toxicology in 2010. The Registry contains data
      from participating sites with the agreement that all bedside medical toxicology
      consultations will be entered. Currently, 83% of accredited medical toxicology
      fellowship programs in the USA participate. The Registry continues to grow each
      year, and as of 31 December 2016, a new milestone was reached, with more than
      50,000 cases reported since its inception. The objective of this seventh annual
      report is to summarize the Registry's 2016 data and activity with its additional
      8529 cases. Cases were identified for inclusion in this report by a query of the
      ToxIC database for any case entered from 1 January to 31 December 2016. Detailed
      data was collected from these cases and aggregated to provide information which
      includes the following: demographics (age, gender, race, ethnicity, HIV status),
      reason for medical toxicology evaluation (intentional pharmaceutical exposure,
      envenomation, withdrawal from a substance), agent and agent class, clinical signs
      and symptoms (vital sign abnormalities, organ system dysfunction), treatments and
      antidotes administered, fatality and life support withdrawal data. Fifty percent
      of cases involved females, and adults aged 19-65 were the most commonly reported.
      There were 86 patients (1.0%) with HIV-positive status known. Non-opioid
      analgesics were the most commonly reported agent class, with acetaminophen the
      most common agent reported. There were 126 fatalities reported in 2016 (1.5% of
      cases). Major trends in demographics and exposure characteristics remained
      similar overall with past years' reports. While treatment interventions were
      commonly required, fatalities were rare.

PMID- 28766241
TI  - Risky Trade: Individual and Neighborhood-Level Socio-Demographics Associated with
      Transactional Sex among Urban African American MSM.
AB  - There is a clear, persistent association between poverty and HIV risk and HIV
      infection. Low educational attainment, neighborhood disadvantage, and residential
      instability are ways in which poverty is instrumentally experienced in urban
      America. We investigated the role of lived poverty at both the individual and
      neighborhood levels in transactional sex behavior among African American men who
      have sex with men (MSM) residing in urban neighborhoods. Using population
      averaged models estimated by generalized estimating equation (GEE) models, we
      identified individual-level and neighborhood-level factors that are associated
      with exchanging sex for drugs and/or money. We tested the association between
      neighborhood and individual-level socioeconomic status and HIV risk behavior by
      combining area-based measures of neighborhood quality from the US Census with
      individual survey data from 542 low-income African American MSM. The primary
      outcome measure was self-reported transactional sex defined as exchanging sex for
      drugs or money. Individual-level covariates included high school non-completion,
      income, and problem drug use. Neighborhood-level covariates were high school non
      completion and poverty rates. The findings suggested that educational attainment
      is associated with both the individual level and neighborhood level. Participants
      were more likely to engage in transactional sex if they did not complete high
      school (OR = 1.78), and similarly if their neighbors did not complete high school
      (OR = 7.70). These findings suggest potential leverage points for both community
      level interventions and advocacy for this population, particularly related to
      transactional sex and education, and will aid HIV prevention efforts that seek to
      address the contextual constraints on individual risk behavior.

PMID- 28766242
TI  - Simultaneous Versus Sequential Side-by-Side Bilateral Metal Stent Placement for
      Malignant Hilar Biliary Obstructions.
AB  - BACKGROUND: Endoscopic bilateral self-expandable metallic stent (SEMS) placement
      for malignant hilar biliary obstructions (MHBOs) is technically demanding, and a
      second SEMS insertion is particularly challenging. A simultaneous side-by-side
      (SBS) placement technique using a thinner delivery system may mitigate these
      issues. AIMS: We aimed to examine the feasibility and efficacy of simultaneous
      SBS SEMS placement for treating MHBOs using a novel SEMS that has a 5.7-Fr ultra
      thin delivery system. METHODS: Thirty-four patients with MHBOs underwent SBS SEMS
      placement between 2010 and 2016. We divided the patient cohort into those who
      underwent sequential (conventional) SBS placement between 2010 and 2014
      (sequential group) and those who underwent simultaneous SBS placement between
      2015 and 2016 (simultaneous group), and compared the groups with respect to the
      clinical outcomes. RESULTS: The technical success rates were 71% (12/17) and 100%
      (17/17) in the sequential and simultaneous groups, respectively, a difference
      that was significant (P = .045). The median procedure time was significantly
      shorter in the simultaneous group (22 min) than in the sequential group (52 min)
      (P = .017). There were no significant group differences in the time to recurrent
      biliary obstruction (sequential group: 113 days; simultaneous group: 140 days) or
      other adverse event rates (sequential group: 12%; simultaneous group: 12%).
      CONCLUSIONS: Simultaneous SBS placement using the novel 5.7-Fr SEMS delivery
      system may be more straightforward and have a higher success rate compared to
      that with sequential SBS placement. This new method may be useful for bilateral
      stenting to treat MHBOs.

PMID- 28766243
TI  - Cost of Illness in Inflammatory Bowel Disease.
AB  - BACKGROUND: Frequent relapses sometimes necessitating hospitalization and the
      absence of pharmacological cure contribute to substantial healthcare costs in
      inflammatory bowel diseases (IBDs). The costs of health care in Indian patients
      with IBD are unknown. AIM: To evaluate the annual costs for treating Crohn's
      disease and ulcerative colitis. METHODS: A prevalence-based, micro-costing method
      was used to assess the components of annual costs in a prospective, observational
      study conducted in a tertiary healthcare center enrolled over a 24-month period
      beginning of July 2014. RESULTS: At enrollment, 43/59 (72.88%) patients with UC
      and 18/25 (72%) with CD were in remission. The annual median (IQR) cost per UC
      and CD patient in remission was INR 43,140 (34,357-51,031) [USD $707 (563-836)]
      and INR 43,763.5 (32,202-57,372) [USD $717 (527-940)], respectively, and in
      active disease was INR 52,436.5 (49,229-67,567.75) [$859 (807-1107)] and INR
      72,145 (49,447-92,212) [USD $1182 (811-1512)], respectively. Compared with
      remission, active disease had a 1.4-fold higher cost for CD as compared to UC. In
      both groups, the greatest component of direct costs was drugs. Thirteen (22%) and
      7 (28%) patients with UC and CD needed hospitalization accounting for 23.1 and
      20.4% of the total costs, respectively. At one year, direct costs surmounted
      indirect costs in UC and CD (p < 0.001). Productivity losses contributed to 18.5
      and 16% of the overall costs for UC and CD, respectively. CONCLUSION: This first,
      panoptic, health economic study for IBD from India shows that the costs are
      driven by medication, productivity losses, and not merely hospitalization alone.

PMID- 28766245
TI  - Elevated Expression of RPA3 Is Involved in Gastric Cancer Tumorigenesis and
      Associated with Poor Patient Survival.
AB  - BACKGROUND: The replication protein A3 (RPA3) is a component of the RPA protein
      complex, which plays an essential role in multiple processes of DNA metabolism.
      AIMS: However, the involvement of RPA3 in gastric cancer tumorigenesis has not
      yet been investigated. METHODS: We stably knocked down RPA3 expression using
      short hairpin RNA in AGS cell line, and performed cell growth, colony formation
      and soft agar assays. Xenograft experiments were performed to examine tumor
      promoting properties of RPA3 in vivo. The qRT-PCR and immunohistochemistry were
      performed to evaluate RPA3 expression levels in 37 and 12 pairs of gastric cancer
      patient samples, respectively. Association between RPA3 expression and survival
      was evaluated in an independent cohort of 85 gastric cancer patients. RESULTS:
      Downregulation of RPA3 inhibited cell growth, clonogenicity and soft agar growth
      in AGS cells. Decreased expression of RPA3 significantly reduced tumor growth
      rate in AGS xenografts. In addition, RPA3 was upregulated in cancerous tissues
      compared with matched noncancerous adjacent tissues in gastric cancer patients.
      High expression of RPA3 was associated with poor patient survival. CONCLUSION:
      Upregulation of RPA3 is involved in gastric cancer tumorigenesis and is
      associated with poorer patient survival. RPA3 represents a new therapeutic target
      of gastric cancer and serves as a potential prognostic biomarker for patient
      survival in gastric cancer.

PMID- 28766244
TI  - Sulfur Cycling and the Intestinal Microbiome.
AB  - In this review, we focus on the activities transpiring in the anaerobic segment
      of the sulfur cycle occurring in the gut environment where hydrogen sulfide is
      produced. While sulfate-reducing bacteria are considered as the principal agents
      for hydrogen sulfide production, the enzymatic desulfhydration of cysteine by
      heterotrophic bacteria also contributes to production of hydrogen sulfide. For
      sulfate-reducing bacteria respiration, molecular hydrogen and lactate are
      suitable as electron donors while sulfate functions as the terminal electron
      acceptor. Dietary components provide fiber and macromolecules that are degraded
      by bacterial enzymes to monomers, and these are fermented by intestinal bacteria
      with the production to molecular hydrogen which promotes the metabolic dominance
      by sulfate-reducing bacteria. Sulfate is also required by the sulfate-reducing
      bacteria, and this can be supplied by sulfate- and sulfonate-containing compounds
      that are hydrolyzed by intestinal bacterial with the release of sulfate. While
      hydrogen sulfide in the intestinal biosystem may be beneficial to bacteria by
      increasing resistance to antibiotics, and protecting them from reactive oxygen
      species, hydrogen sulfide at elevated concentrations may become toxic to the
      host.

PMID- 28766246
TI  - Can Cardiovascular Epidemiology and Clinical Trials Close the Risk Management Gap
      Between Diabetes and Prediabetes?
AB  - PURPOSE OF REVIEW: We reviewed published literature to determine the relationship
      between A1c and cardiovascular disease (CVD) and summarize the need and
      implications for CVD risk reduction with interventions, focusing in the
      prediabetic A1c range (<6.5%). RECENT FINDINGS: Strong evidence supports a
      continuous relationship between A1c and CVD-even below the current levels of A1c
      defined prediabetes and after adjustment for known risk factors for CVD. Clinical
      trials have demonstrated a reduction in CV morbidity and/or mortality when
      interventions are invoked in the prediabetic A1c range. Guidelines advocating CV
      risk factor management in prediabetes have not been widely adopted, subsequently
      leading to comparable coronary heart disease risk between people with prediabetes
      (HR = 1.9, 95% CI 1.7-2.1 vs normoglycemia) and diabetes itself (HR=2.0, 95% CI
      1.8-2.2 vs no diabetes). This review highlights the missed opportunity to utilize
      multiple risk factor interventions to reduce CVD in high-risk people with
      prediabetes.

PMID- 28766248
TI  - Roman Catholic Priests as Referral Sources and Treatment Aides for Hispanics with
      Substance Misuse/Abuse Problems.
AB  - This self-administered mail survey study, conducted along the USA-Mexico border,
      examines Roman Catholic Priests' involvement in aiding Hispanic individuals with
      substance abuse problems. The Priests were found to be highly involved or willing
      to be involved in: (1) participating in juramentos (pledge usually to Virgin of
      Guadalupe, with Priest as witness, to temporarily abstain from substance use),
      (2) providing referrals, and (3) working with family and/or treatment resources
      in the community in order to help the person seeking their help. Fluency in
      Spanish, regardless of Hispanic ethnicity, was found to positively impact
      involvement in juramentos, providing referrals, and willingness to work with
      community resources.

PMID- 28766247
TI  - Cigarette Smoking, Diabetes, and Diabetes Complications: Call for Urgent Action.
AB  - PURPOSE OF REVIEW: This review aimed to examine the latest evidence linking
      cigarette smoking and cessation to risk of incident diabetes and its
      complications. RECENT FINDINGS: Abundant evidence has demonstrated that smoking
      is associated with increased risk of type 2 diabetes and cardiovascular disease
      among diabetic patients, while its relationship with microvascular complications
      is more limited to diabetic nephropathy and neuropathy in type 1 diabetes. In
      addition, diabetes risk remains high in the short term after smoking cessation,
      while it reduces gradually in the long term. Risk of cardiovascular complications
      also substantially decreases after quitting smoking, but results for
      microvascular complications are not consistent. Smoking is associated with
      increased risks of incident diabetes in the general population and cardiovascular
      complications among diabetic patients. Although the short-term post-cessation
      diabetes risk needs to be acknowledged, this review calls for urgent action to
      implement population-wide policies and individual pharmaceutical and lifestyle
      interventions (if evidence accumulated in future) to aid smoking cessation and
      prevent diabetes and its complications.

PMID- 28766249
TI  - If Abortion, then Infanticide.
AB  - Our contention is that all of the major arguments for abortion are also arguments
      for permitting infanticide. One cannot distinguish the fetus from the infant in
      terms of a morally significant intrinsic property, nor are they morally
      discernible in terms of standing in different relationships to others. The logic
      of our position is that if such arguments justify abortion, then they also
      justify infanticide. If we are right that infanticide is not justified, then such
      arguments will fail to justify abortion. We respond to those philosophers who
      accept infanticide by putting forth a novel account of how the mindless can be
      wronged which serves to distinguish morally significant potential from morally
      irrelevant potential. This allows our account to avoid the standard objection
      that many entities possess a potential for personhood which we are intuitively
      under no obligation to further or protect.

PMID- 28766250
TI  - Exploring the Histogenesis and Diagnostic Strategy Using Immunoassay and RT-PCR
      in Alveolar Soft Part Sarcoma.
AB  - Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma, but it's easily
      misdiagnosed in rare locations. The derivation of ASPS is still uncertain,
      therefore we conducted this study to explore the histogenesis of ASPS by
      analyzing stem cell markers (ALDH1, CD29, CD133 and Nestin). Protein TFE3 and
      fusion gene ASPS-TFE3 were tested in paraffin to explore diagnostic strategy and
      molecular pathological features. In this study, nine cases of ASPS were
      immunostained with stem cell surface markers (ALDH1, CD29, CD133 and Nestin) and
      protein TFE3. Seven cases of ASPS mRNA were successfully extracted from nine
      paraffin-embedded tissues. The expression of fusion gene ASPL-TFE3 was examined
      by reverse transcriptase-polymerase chain reaction. The immunohistochemical
      staining of nine patients showed that CD29 and Nestin were negative in all nine
      cases (0/9). CD133 was weakly positive in one cases (1/9) and ALDH1 was weakly
      positive in one cases (1/9). TFE3 was positive in nine cases (9/9). Seven
      paraffin tissues could be successfully extracted with mRNA in nine cases. The
      results of Reverse Transcription Polymerase Chain Reaction (RT-PCR) showed that
      ASPL-TFE3 fusion transcripts could be tested in the seven cases (four cases being
      type 2 and three cases being type 1). The positive rate of CD133 and ALDH1 were
      less than 1% and the expression of CD29 and Nestin were negative in ASPS.
      Immunohistochemistry results indicated that the histogenesis of ASPS maybe not
      derive from mesenchymal stem cells. Immunohistochemistry staining showed that
      TFE3 protein expression was highly sensitive in ASPS. Furthermore, RT-PCR results
      showed that fusion gene ASPL-TFE3 (ASPL-TFE3 type 1 and ASPL-TFE3 type 2) was
      expressed in ASPS, which could provide information for clinical molecular
      pathological diagnosis and improve the diagnosis rate of rare atypical ASPS.

PMID- 28766252
TI  - The Machine Days Are Over: Medicine Metaphors and the Psychiatric Resident.

PMID- 28766251
TI  - Melatonin Alleviates Intracerebral Hemorrhage-Induced Secondary Brain Injury in
      Rats via Suppressing Apoptosis, Inflammation, Oxidative Stress, DNA Damage, and
      Mitochondria Injury.
AB  - Intracerebral hemorrhage (ICH) is a cerebrovascular disease with high mortality
      and morbidity, and the effective treatment is still lacking. We designed this
      study to investigate the therapeutic effects and mechanisms of melatonin on the
      secondary brain injury (SBI) after ICH. An in vivo ICH model was induced via
      autologous whole blood injection into the right basal ganglia in Sprague-Dawley
      (SD) rats. Primary rat cortical neurons were treated with oxygen hemoglobin
      (OxyHb) as an in vitro ICH model. The results of the in vivo study showed that
      melatonin alleviated severe brain edema and behavior disorders induced by ICH.
      Indicators of blood-brain barrier (BBB) integrity, DNA damage, inflammation,
      oxidative stress, apoptosis, and mitochondria damage showed a significant
      increase after ICH, while melatonin reduced their levels. Meanwhile, melatonin
      promoted further increasing of expression levels of antioxidant indicators
      induced by ICH. Microscopically, TUNEL and Nissl staining showed that melatonin
      reduced the numbers of ICH-induced apoptotic cells. Inflammation and DNA damage
      indicators exhibited an identical pattern compared to those above. Additionally,
      the in vitro study demonstrated that melatonin reduced the apoptotic neurons
      induced by OxyHb and protected the mitochondrial membrane potential.
      Collectively, our investigation showed that melatonin ameliorated ICH-induced SBI
      by impacting apoptosis, inflammation, oxidative stress, DNA damage, brain edema,
      and BBB damage and reducing mitochondrial membrane permeability transition pore
      opening, and melatonin may be a potential therapeutic agent of ICH.

PMID- 28766253
TI  - Imaging assessment of bioresorbable vascular scaffolds.
AB  - Vascular reparative therapy has become a reality with bioresorbable scaffolds
      (BRSs). To assess acute and long-term performance of the device, multimodality
      imaging would be essential. Radiopacity of metal hinders the imaging assessment,
      whereas radiolucent polymeric scaffolds allow for a precise imaging assessment
      with either invasive or non-invasive modality at baseline and at follow-up, which
      is one of the advantages of polymeric BRSs. Recent large trials evaluating
      clinical results of the first-generation BRS technology raised concerns about the
      safety and efficacy of these devices, namely, scaffold thrombosis. Intensive
      research with multimodality imaging in the field is being conducted to have in
      depth understanding of the issues, which will facilitate the improvement of
      implantation techniques and the development of the next-generation BRSs. The
      current review focuses on the clinical application of the imaging modalities to
      assess the short- and long-term performance of the Absorb BVS.

PMID- 28766255
TI  - Erratum to: Fragment-based in silico modeling of multi-target inhibitors against
      breast cancer-related proteins.

PMID- 28766254
TI  - VEGF-Mediated Cognitive and Synaptic Improvement in Chronic Cerebral
      Hypoperfusion Rats Involves Autophagy Process.
AB  - Chronic cerebral hypoperfusion (CCH) is associated with various neurodegenerative
      diseases characterized by cognitive impairment. Dozens of studies including ours
      have indicated that exogenous administration of vascular endothelial growth
      factor (VEGF) could exert effective cognitive protection during ischemia.
      Nevertheless, the underlying mechanism has not been well clarified. To address
      this issue, we explored the synaptic mechanisms in vivo since hippocampal
      synaptic function is essential to the learning and memory process. Besides, the
      role of autophagy in cognitive dysfunction under conditions of CCH is still
      controversial. And abnormal autophagy could threaten normal neurotransmission at
      synapse where a large amount of protein synthesis and degradation take place.
      Hence, we further examined whether the altered synaptic function was associated
      with autophagy. The results showed that CCH impaired spatial cognition as
      evidenced in Morris water maze. We further found that VEGF mitigated impaired
      hippocampal synaptic function including basal synaptic transmission, paired-pulse
      facilitation, short-term, long-term plasticity, depotentiation, and the level of
      synaptic proteins as assessed by electrophysiological examination and western
      blot assay. Furthermore, our results demonstrated that CCH could induce excessive
      autophagy which could be inhibited by VEGF. Thus, we speculated that VEGF could
      ameliorate impaired synaptic function induced by CCH because of its ability to
      inhibit excessive autophagy, and eventually improve spatial learning and memory
      function. Importantly, our findings shed light on potential therapeutic
      strategies to be exploited in the usage of VEGF.

PMID- 28766256
TI  - Synthesis, insecticidal activities and structure-activity relationship study of
      dual chiral sulfilimines.
AB  - To investigate the "methyl" impact on bioactivity of sulfiliminyl dicarboxamides,
      a total of 16 novel N-cyano and N-trifluoroacetyl sulfiliminyl dicarboxamides
      containing m-heptafluoroisopropylated aromatic amino moiety were studied. Two
      series of sulfiliminyl substituents were designed, synthesized and evaluated
      against oriental armyworm (Pseudaletia separata Walker) for their insecticidal
      activities. Their chemical structures were established by corresponding [Formula:
      see text] NMR, HRMS and optical polarimetry. Bioassay results revealed that some
      of the title compounds showed potent insecticidal activities against oriental
      armyworm. Notably, compounds IIa, IIIa, IVa exhibited 100% activity at [Formula:
      see text], in particular, IIa showed a comparable control efficacy to that of the
      commercial product flubendiamide. The SAR of these N-cyano sulfiliminyl isomers
      can be summarized as follows (Sc, Ss) [Formula: see text] (Sc, Rs), while the N
      trifluoroacetyl sulfiliminyl isomers is (Sc, Rs) [Formula: see text] (Sc, Ss).
      Comparative molecular field analysis indicated that an electropositive
      substituent, [Formula: see text] group in the benzene ring was very important for
      the improvement in biological activity. These results could hold promise for
      novel chiral sulfiliminyl RyR regulators.

PMID- 28766257
TI  - DBU-catalyzed, aromatization-oriented, regioselective domino synthesis of 2
      aminopyrimidines from beta-dicarbonyl compounds, DMF-DMA, and cyanamide.
AB  - A multicomponent domino synthesis has been developed for the preparation of 2
      aminopyrimidines from beta-dicarbonyl compounds, N,N-dimethylformamide dimethyl
      acetal, and cyanamide. The protocol was used for the regioselective preparation
      of 4-amide/ester/ketone substituted 2-aminopyrimidines. Twelve 2-aminopyrimidines
      were isolated in good yields (56-93%).

PMID- 28766258
TI  - Panicle blast 1 (Pb1) resistance is dependent on at least four QTLs in the rice
      genome.
AB  - BACKGROUND: Rice blast is the most serious disease afflicting rice and there is
      an urgent need for the use of disease resistance (R) genes in blast tolerance
      breeding programs. Pb1 is classified as a quantitative resistance gene and it
      does not have fungal specificity. Pb1-mediated resistance develops in the latter
      stages of growth. However, some cultivars, such as Kanto209 (K209), cultivar name
      Satojiman, despite possessing Pb1, do not exert resistance to rice blast during
      the reproductive stage. RESULTS: We found that the expression of WRKY45 gene
      downstream of Pb1 was weakly induced by rice blast inoculation at the full
      heading stage in K209. Genetic analysis using the SNP-based Golden Gate assay of
      K209 crossing with Koshihikari Aichi SBL (KASBL) found at least four regions
      related to the resistance in the rice genome (Chr8, Chr9, Chr7, Chr11). Mapping
      of QTL related to Chr7 confirmed the existence of factors that were required for
      the resistance of Pb1 in the 22 to 23 Mbp region of the rice genome. CONCLUSION:
      We clarified how the K209 cultivar is vulnerable to the blast disease despite
      possessing Pb1 and found the DNA marker responsible for the quantitative
      resistance of Pb1. We identified the QTL loci required for Pb1-mediated
      resistance to rice panicle blast. Pb1 was negatively dependent on at least three
      QTLs, 7, 9 and 11, and positively dependent on one, QTL 8, in the K209 genome.
      This finding paves the way for creating a line to select optimal QTLs in order to
      make use of Pb1-mediated resistance more effectively.

PMID- 28766259
TI  - Male body dissatisfaction scale (MBDS): proposal for a reduced model.
AB  - AIMS: To evaluate the psychometric properties of the male body dissatisfaction
      scale (MBDS) in Brazilian and Portuguese university students; to present a
      reduced model of the scale; to compare two methods of computing global scores for
      participants' body dissatisfaction; and to estimate the prevalence of
      participants' body dissatisfaction. METHODS: A total of 932 male students
      participated in this study. A confirmatory factor analysis (CFA) was used to
      assess the scale's psychometric properties. Multi-group analysis was used to test
      transnational invariance and invariance in independent samples. The body
      dissatisfaction score was calculated using two methods (mean and matrix of
      weights in the CFA), which were compared. Finally, individuals were classified
      according to level of body dissatisfaction, using the best method. RESULTS: The
      MBDS model did not show adequate fit for the sample and was, therefore, refined.
      Thirteen items were excluded and two factors were combined. A reduced model of 12
      items and 2 factors was proposed and shown to have adequate psychometric
      properties. There was a significant difference (p < 0.001) between the methods
      for calculating the score for body dissatisfaction, since the mean overestimated
      the scores. Among student participants, the prevalence of body dissatisfaction
      with musculature and general appearance was 11.2 and 5.3%, respectively.
      CONCLUSIONS: The reduced bi-factorial model of the MBDS showed adequate validity,
      reliability, and transnational invariance and invariance in independent samples
      for Brazilian and Portuguese students. The new proposal for calculating the
      global score was able to more accurately show their body dissatisfaction. No
      level of evidence Basic Science.

PMID- 28766260
TI  - Erratum to: MDMA-induced indifference to negative sounds is mediated by the 5
      HT2A receptor.

PMID- 28766261
TI  - The excessive response: a preparation for harder conditions.

PMID- 28766262
TI  - Response requirements affect offside judgments in football (soccer).
AB  - Judging offside in football represents a typical go-nogo task (offside-raising
      the flag, no offside-no response). Nevertheless, several studies involved two
      choice tasks (e.g. offside-press key A, no offside-press key B) to investigate
      potential sources of errors in offside situations. While go-nogo and choice
      response tasks are commonly used in experimental psychology, response preferences
      may differ between the two tasks. Therefore, we investigated the impact of
      response requirements on offside judgments in a sample of male participants
      without experience in professional refereeing. Each participant judged displays
      of potential offside situations in a go-nogo condition and in a two-choice
      condition. The results show that response requirements affected the response bias
      of the participants and suggest that go-nogo requirements increase the preference
      for the positive response (i.e. the offside response) as compared to the two
      choice task. We discuss both methodological and theoretical implications of this
      finding.

PMID- 28766263
TI  - A phase II study of combination therapy with oral S-1 and cisplatin in elderly
      patients with advanced gastric cancer.
AB  - BACKGROUND: A combination of S-1 and cisplatin is recognized as one of the
      standard first-line chemotherapy regimens for patients with advanced gastric
      cancer. However, demographic analyses of pivotal phase III studies have showed
      that only a minority of treated patients were aged 76 years or older. The purpose
      of this phase II study was to evaluate the safety and efficacy of combination
      therapy with S-1 and cisplatin in elderly patients with chemotherapy-naive
      advanced gastric cancer. METHODS: Patients aged 76 years or older received S-1 40
      mg/m2 orally twice daily for 21 days and cisplatin 60 mg/m2 intravenously infused
      at day 8 of each 35-day cycle. Dose modification was performed according to
      creatinine clearance. The primary endpoint was overall survival (OS). Secondary
      endpoints included response rate, progression-free survival (PFS), time to
      treatment failure (TTF), and adverse events. RESULTS: A total of 40 patients were
      enrolled. Median OS was 12.3 months, PFS was 7.8 months, and TTF was 4.3 months.
      The response rate was 54%. The most common grade 3-4 adverse events were anorexia
      (25%), neutropenia (23%), hyponatremia (20%), anemia (18%), and febrile
      neutropenia (8%). No treatment-related death occurred. CONCLUSIONS: Combination
      chemotherapy with S-1 and cisplatin is an effective and well-tolerated regimen
      for elderly patients with advanced gastric cancer when the dose is adjusted
      according to renal function.

PMID- 28766264
TI  - Acetaminophen (Paracetamol) Induces Hypothermia During Acute Cold Stress.
AB  - BACKGROUND: Acetaminophen is an over-the-counter drug used to treat pain and
      fever, but it has also been shown to reduce core temperature (T c) in the absence
      of fever. However, this side effect is not well examined in humans, and it is
      unknown if the hypothermic response to acetaminophen is exacerbated with cold
      exposure. OBJECTIVE: To address this question, we mapped the thermoregulatory
      responses to acetaminophen and placebo administration during exposure to acute
      cold (10  degrees C) and thermal neutrality (25  degrees C). METHODS: Nine
      healthy Caucasian males (aged 20-24 years) participated in the experiment. In a
      double-blind, randomised, repeated measures design, participants were passively
      exposed to a thermo-neutral or cold environment for 120 min, with administration
      of 20 mg/kg lean body mass acetaminophen or a placebo 5 min prior to exposure. T
      c, skin temperature (T sk), heart rate, and thermal sensation were measured every
      10 min, and mean arterial pressure was recorded every 30 min. Data were analysed
      using linear mixed effects models. Differences in thermal sensation were analysed
      using a cumulative link mixed model. RESULTS: Acetaminophen had no effect on T c
      in a thermo-neutral environment, but significantly reduced T c during cold
      exposure, compared with a placebo. T c was lower in the acetaminophen compared
      with the placebo condition at each 10-min interval from 80 to 120 min into the
      trial (all p < 0.05). On average, T c decreased by 0.42 +/- 0.13  degrees C from
      baseline after 120 min of cold exposure (range 0.16-0.57  degrees C), whereas
      there was no change in the placebo group (0.01 +/- 0.1  degrees C). T sk, heart
      rate, thermal sensation, and mean arterial pressure were not different between
      conditions (p > 0.05). CONCLUSION: This preliminary trial suggests that
      acetaminophen-induced hypothermia is exacerbated during cold stress. Larger scale
      trials seem warranted to determine if acetaminophen administration is associated
      with an increased risk of accidental hypothermia, particularly in vulnerable
      populations such as frail elderly individuals.

PMID- 28766265
TI  - Laparoscopic Sleeve Gastrectomy for Morbid Obesity in Patients After Orthotopic
      Liver Transplant: a Matched Case-Control Study.
AB  - INTRODUCTION: Obesity is frequently encountered in patients with orthotopic liver
      transplant (OLT). The role of bariatric surgery is still unclear for this
      specific population. The aim of this study was to review our experience with
      laparoscopic sleeve gastrectomy (LSG) after OLT. MATERIAL AND METHODS: We
      performed a retrospective case-control study of patients undergoing LSG after OLT
      from 2010 to 2016. OLT-LSG patients were matched by age, sex, body mass index
      (BMI), and year to non-OLT patients undergoing LSG. Demographics, operative
      variables, postoperative events, and long-term weight loss with comorbidity
      resolution were collected and compared between cases and controls. RESULTS: Of
      303 patients undergoing LSG, 12 (4%) had previous OLT. They were matched to 36
      non-OLT patients. No difference was found between groups in the American Society
      of Anesthesiologists class, mean operative time, or postoperative morbidity. The
      non-OLT group, however, had a significantly shorter mean hospital stay than the
      OLT group (1.7 vs 3.1 days; P < .001). There were no conversions to open
      procedures. For patients with long-term follow-up, change in BMI after LSG was
      similar between the groups, but the non-OLT patients had significantly more
      excess body weight loss at 2 years (53.7 vs 45.2%; P < .001). Similar resolution
      of comorbid conditions was noted in both groups. LSG caused no changes in dosage
      of immunosuppressive medications, and no liver complications occurred.
      CONCLUSION: LSG after OLT in appropriately selected patients appears to have
      similar outcomes to LSG in non-OLT patients.

PMID- 28766266
TI  - Utility of Bile Acid Scintigraphy in the Diagnosis of Remnant Gastropathy in
      Patients with Roux-en-Y Gastric Bypass.

PMID- 28766268
TI  - Unusual timing of a common complication after pulmonary vein isolation.

PMID- 28766267
TI  - Iodine Status After Bariatric Surgery-a Prospective 10-Year Report from the
      Swedish Obese Subjects (SOS) Study.
AB  - CONTEXT: Bariatric surgery can lead to nutrient deficiencies. Gastric by-pass
      (GBP) entails restriction and malabsorption, whereas, vertical banded
      gastroplasty (VBG) is only restrictive. OBJECTIVE: The objective of this study is
      to study whether GBP-patients develop iodine deficiency from malabsorption, and
      if GBP- and VBG-patients develop lower 24-h urinary iodine excretion (24-UIE)
      than obese non-operated controls (OB-controls) due to lower iodine intake.
      DESIGN: The Swedish Obese Subjects (SOS) study is a prospective, non-randomized
      study of 4047 obese patients included 1987-2001, who chose bariatric surgery or
      non-surgical treatment. SOS-groups were compared at baseline, after 2 and 10
      years and with population-based subsamples (MONICA-controls). PATIENTS: One
      hundred eighty-eight GBP-patients were matched with 188 VBG-patients and 188 OB
      controls and with three subgroups from 412 MONICA-controls. MAIN OUTCOME
      MEASUREMENTS: Primary outcome was 24-UIE. Secondary outcomes were iodine intake,
      iodine supplementation, TSH, FT4, and thyroid morbidity. RESULTS: At baseline,
      median 24-UIE was higher in GBP-patients, VBG-patients and OB-controls than in
      MONICA-controls (214, 201, 203 and 137 MUg/day, p < 0.001). At 10 years, 24-UIE
      in GBP-patients (161 MUg/day) and VBG-patients (149 MUg/day) was lower compared
      with baseline (p < 0.01) and OB-controls (189 MUg/day, p < 0.01), but similar to
      24-UIE in MONICA-controls (137 MUg/day). The 10-year-dietary iodine intake was
      similar in GPB-patients and OB-controls, but higher in VBG-patients. Iodine
      supplementation was taken by 0-9% in SOS-groups. CONCLUSION: After surgery, GBP-
      and VBG-patients did not suffer from iodine deficiency, but both groups had lower
      iodine status than OB-controls. Dietary supplements recommended after bariatric
      surgery do not need to include iodine, in iodine sufficient countries. TRIAL
      REGISTRATION: clinicaltrials.gov : NCT01479452.

PMID- 28766269
TI  - Analysis of Neurotoxic Amino Acids from Marine Waters, Microbial Mats, and
      Seafood Destined for Human Consumption in the Arabian Gulf.
AB  - Human health risks associated with exposure to algal and cyanobacterial toxins
      (phycotoxins) have been largely concerned with aquatic habitats. People
      inhabiting desert environments may be exposed to phycotoxins present in
      terrestrial environments, where cyanobacterial crusts dominate. Seafood comprises
      a significant portion of the human diet in desert environments proximal to an
      ocean or sea. Consequently, in addition to terrestrial exposure to cyanotoxins,
      the potential exists that seafood may be an important exposure route for
      cyanotoxins in desert regions. Understanding the possible risk of exposure from
      seafood will help create cyanotoxin health guidelines for people living in
      environments that rely on seafood. Commonly-consumed local seafood products
      destined for human consumption were purchased from a fish market in Doha, Qatar.
      Organs were excised, extracted, and analyzed for the neurotoxic amino acid beta-N
      methylamino-L-alanine (BMAA) and the isomers 2,4-diaminobutyric acid (DAB) and N
      2(aminoethyl)glycine (AEG). The presence and concentration of neurotoxic amino
      acids were investigated in organisms from various trophic levels to examine the
      potential for biomagnification. Although BMAA and isomers were detected in marine
      microbial mats, as well as in marine plankton net trawls associated with diatoms
      and dinoflagellates, in seafood, only AEG and DAB were present at low
      concentrations in various trophic levels. The findings of this study suggest that
      exposure to neurotoxic amino acids through seafood in the Arabian Gulf may be
      minor, yet the presence of BMAA in phytoplankton confirms the need for further
      monitoring of marine waters and seafood to protect human health.

PMID- 28766270
TI  - Oxytocin and Autism Spectrum Disorders.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose core
      symptoms include deficits in social interaction and communication besides
      restricted and repetitive behaviors. Although ASD is highly prevalent, affecting
      1/100 in the general population, no medication for the core symptoms has been
      established. Therefore, the disorder is considered a huge unmet medical need and
      a heavy burden on individuals with ASD, their families, and entire society.
      Oxytocin is expected to be a potential therapeutic resource for the social core
      symptoms of ASD, since this neuropeptide can modulate human social behavior and
      cognition. This review article provides an overview of both experimental and
      clinical studies on effects of oxytocin administration on behavior, neural
      underpinnings, and symptomatology of ASD. Although the number of studies is
      increasing, several issues remain for further development of clinical application
      of the neuropeptide. The issues include optimization of administration route,
      doses, treatment duration, interval of administrations, and timing of starting
      treatment. Additional issues involve investigating neurobiological mechanisms of
      treatment and developing a reliable tool to accurately and objectively assess
      longitudinal changes in the core symptoms of ASD. Some of these issues are
      discussed in this review.

PMID- 28766271
TI  - Rapid Liver Hypertrophy After Portal Vein Occlusion Correlates with the Degree of
      Collateralization Between Lobes-a Study in Pigs.
AB  - BACKGROUND: Associating liver partition and portal vein ligation for staged
      hepatectomy (ALPPS) induces more rapid liver growth than portal vein ligation
      (PVL). Transection of parenchyma in ALPPS may prevent the formation of
      collaterals between lobes. The aim of this study was to determine if abrogating
      the formation of collaterals through parenchymal transection impacted growth
      rate. METHODS: Twelve Yorkshire Landrace pigs were randomized to undergo ALPPS,
      PVL, or "partial ALPPS" by varying degrees of parenchymal transection. Hepatic
      volume was measured after 7 days. Portal blood flow and pressure were measured.
      Portal vein collaterals were examined from epoxy casts. RESULTS: PVL, ALPPS, and
      partial ALPPS led to volume increases of the RLL by 15.5% (range 3-22), 64%
      (range 45-76), and 32% (range 18-77), respectively, with significant differences
      between PVL and ALPPS/partial ALPPS (p < 0.05). In PVL and partial ALPPS,
      substantial new portal vein collaterals were found. The number of collaterals
      correlated inversely with the growth rate (p = 0.039). Portal vein pressure was
      elevated in all models after ligation suggesting hyperflow to the portal vein
      supplied lobe (p < 0.05). CONCLUSIONS: These data suggest that liver hypertrophy
      following PVL is inversely proportional to the development of collaterals.
      Hypertrophy after ALPPS is likely more rapid due to reduction of collaterals
      through transection.

PMID- 28766272
TI  - Laparoscopic Distal Pancreatectomy for Cancer Provides Oncologic Outcomes and
      Overall Survival Identical to Open Distal Pancreatectomy.
AB  - BACKGROUND: Laparoscopic distal pancreatectomy (LDP) has been shown to provide
      short-term clinical outcomes similar to open distal pancreatectomy (ODP) for
      patients with benign tumors. Our aim was to better define oncologic outcomes and
      long-term survival profiles following LDP for pancreatic ductal adenocarcinoma
      (PDAC). METHODS: We queried the National Cancer Database to identify patients
      with pathologic stage I-III PDAC who underwent distal pancreatectomy between 2010
      and 2013. Logistic regression was performed to examine predictors of oncologic
      outcomes. Cox modeling was used for survival analysis and to estimate median
      overall survival (OS). RESULTS: One thousand five hundred fifty-four patients
      were included in the analysis. Patients undergoing LDP and ODP demonstrated
      identical probabilities of an adequate lymph node sampling and 90-day mortality.
      Those undergoing LDP demonstrated an increased probability of margin-negative
      resection (OR 1.78, CI 1.25-2.52) and a decreased probability of a prolonged
      hospital stay (OR 0.55, CI 0.32-0.95) or readmission (OR 0.56, CI 0.33-0.95)
      relative to those undergoing ODP. There was no difference in OS between groups
      (29.6 vs. 23.8 months, p = 0.10). CONCLUSION: LDP is an effective modality for
      managing resectable cancer in the pancreatic body and tail. LDP provides short
      term oncologic outcomes and long-term OS rates identical to those for ODP while
      affording an accelerated recovery.

PMID- 28766274
TI  - Pathogen or contaminant? Distinguishing true infection from synovial fluid
      culture contamination in patients with suspected septic arthritis.
AB  - BACKGROUND: Isolation of bacteria from synovial fluid (SF) is the gold standard
      for diagnosis of septic arthritis (SA). Contamination results in misdiagnosis and
      mismanagement. This study identifies clinical characteristics, microbiology, and
      outcomes of patients with contaminated SF and compares them with patients with
      true SA. METHODS: We conducted a retrospective study including all patients aged
      18 and older admitted to a single, tertiary-care hospital between 1998 and 2015
      with suspected SA and positive SF cultures. Contamination cases were determined
      by infectious disease specialists involved in the patients' care and a clinical
      course inconsistent with SA. RESULTS: 398 patients with true SA and 22 with
      contaminated SF were identified. The SA group was younger (60.9 vs. 75.6 years; p
      < 0.01), had higher peripheral polymorphonuclear lymphocytes (78.0 vs. 69.4%; p <
      0.01) and SF white blood cell count (91.7 vs. 25.6K/mL; p = 0.02), and longer
      mean length of stay (10.9 vs. 6.7 days; p = 0.02). The average time to positive
      culture was longer in the contaminated group (3.62 vs. 1.4 days; p < 0.01). The
      SA group was less likely to receive a new rheumatologic diagnosis within 1 year
      (3.0 vs. 36.4%; p < 0.01). CONCLUSION: This is the first study of its kind
      looking at clinical features and outcomes of patients with contaminated SF. These
      patients present with less severe disease, have better outcomes, and receive new
      rheumatologic diagnoses in more than a third of cases within 1 year. We recommend
      a conservative approach for patients with suspected contaminated SF, mild
      symptoms, and no bacterial growth within the first 48 h.

PMID- 28766273
TI  - Pregnancy: Effect on Multiple Sclerosis, Treatment Considerations, and
      Breastfeeding.
AB  - Multiple sclerosis (MS) commonly affects women in childbearing years making
      pregnancy issues important for patients with MS and their families. Pregnancy is
      a naturally occurring disease modifier of MS associated with a 70% reduction in
      relapse rates in the third trimester. This relapse rate reduction during the last
      trimester is roughly equal to the most effective disease-modifying treatments for
      MS. Given this efficacy, various pregnancy factors have been tested to determine
      which play a part in pregnancy's protection, and some have been translated to
      completed and ongoing phase II clinical trials. In contrast to protective effects
      during pregnancy, the postpartum period entails increased relapse risk, which may
      be due to either abrupt removal of protective pregnancy factors after delivery or
      to unique deleterious factors inherent to the postpartum period. The effect of
      breastfeeding on MS remains unclear. The best predictor for whether a patient
      will have a postpartum relapse is the incidence of her having active relapsing MS
      prior to pregnancy. The medical management of MS during pregnancy and the
      postpartum period is challenging given the risks of medication exposure to the
      fetus in utero and to the infant through breast milk. This review will focus on
      clinical aspects of pregnancy, including the effects of pregnancy on MS disease
      activity, as well as the medical management of MS during pregnancy and
      postpartum.

PMID- 28766275
TI  - A mini-invasive tenolysis of the flexor tendons following hand fractures: case
      series.
AB  - INTRODUCTION: The treatment of the flexor tendon adhesions following phalanx and
      metacarpal fractures, in closed or open injuries, is a great challenge for the
      hand surgeon. The outcomes are often poor, because of the severity of the lesion
      and the aggressiveness of the surgical procedure of the secondary tenolysis.
      MATERIALS AND METHODS: The authors describe the technical findings and the
      results of a new mini-invasive tenolysis in order to treat the adhesions in zone
      1 and 2 of the fingers, following phalangeal and metacarpal fractures. With an
      atraumatic Allis or Duval surgical forceps, the flexor tendons are separately and
      gently tracted making a twisting movement on themselves until the adhesions were
      torn and the tendons appeared released. RESULTS: The relevant outcomes achieved
      show this technique is very useful to treat tendon adhesions, without adding
      trauma and scare to the tendinous canal and surrounding soft tissues.

PMID- 28766276
TI  - Impact of membrane lung surface area and blood flow on extracorporeal CO2 removal
      during severe respiratory acidosis.
AB  - BACKGROUND: Veno-venous extracorporeal CO2 removal (vv-ECCO2R) is increasingly
      being used in the setting of acute respiratory failure. Blood flow rates through
      the device range from 200 ml/min to more than 1500 ml/min, and the membrane
      surface areas range from 0.35 to 1.3 m2. The present study in an animal model
      with similar CO2 production as an adult patient was aimed at determining the
      optimal membrane lung surface area and technical requirements for successful vv
      ECCO2R. METHODS: Four different membrane lungs, with varying lung surface areas
      of 0.4, 0.8, 1.0, and 1.3m2 were used to perform vv-ECCO2R in seven anesthetized,
      mechanically ventilated, pigs with experimentally induced severe respiratory
      acidosis (pH 7.0-7.1) using a 20Fr double-lumen catheter with a sweep gas flow
      rate of 8 L/min. During each experiment, the blood flow was increased stepwise
      from 250 to 1000 ml/min. RESULTS: Amelioration of severe respiratory acidosis was
      only feasible when blood flow rates from 750 to 1000 ml/min were used with a
      membrane lung surface area of at least 0.8 m2. Maximal CO2 elimination was 150.8
      ml/min, with pH increasing from 7.01 to 7.30 (blood flow 1000 ml/min; membrane
      lung 1.3 m2). The membrane lung with a surface of 0.4 m2 allowed a maximum CO2
      elimination rate of 71.7 mL/min, which did not result in the normalization of pH,
      even with a blood flow rate of 1000 ml/min. Also of note, an increase of the
      surface area above 1.0 m2 did not result in substantially higher CO2 elimination
      rates. The pressure drop across the oxygenator was considerably lower (<10 mmHg)
      in the largest membrane lung, whereas the smallest revealed a pressure drop of
      more than 50 mmHg with 1000 ml blood flow/min. CONCLUSIONS: In this porcine
      model, vv-ECCO2R was most effective when using blood flow rates ranging between
      750 and 1000 ml/min, with a membrane lung surface of at least 0.8 m2. In
      contrast, low blood flow rates (250-500 ml/min) were not sufficient to completely
      correct severe respiratory acidosis, irrespective of the surface area of the
      membrane lung being used. The converse was also true, low surface membrane lungs
      (0.4 m2) were not capable of completely correcting severe respiratory acidosis
      across the range of blood flows used in this study.

PMID- 28766277
TI  - A review on use of botulinum toxin for intractable lacrimal drainage disorders.
AB  - PURPOSE: To review the published literature on botulinum toxin (BTX) for epiphora
      secondary to refractory lacrimal drainage disorders. METHODS: The authors
      performed a Pub Med search of all articles published in English on BTX injection
      into lacrimal gland for epiphora secondary to lacrimal drainage disorders.
      Relevant cross-references were obtained from the resultant studies. Data reviewed
      included demographics, indications, dose of BTX, number of injections,
      transconjunctival or transcutaneous route, outcomes and complications. Animal
      experiments of BTX into lacrimal gland were included and analyzed separately.
      RESULTS: Botulinum toxin injection into lacrimal gland, in animal studies, has
      shown to reduce the tear volume significantly lasting for approximately a month
      without any histological changes. The major indications have been refractory
      canalicular obstructions and functional epiphora. The commonly used dose was 2.5
      U. Outcomes in the few studies published are encouraging with transient ptosis
      being the most common complication. CONCLUSIONS: Botulinum toxin into the
      lacrimal gland is a minimally invasive alternative in cases of refractory
      epiphora secondary to lacrimal drainage disorders. In these subsets of patients,
      the reported concentrations, dosage and outcome measures are variable and need
      larger studies for standardization.

PMID- 28766278
TI  - OCT angiography demonstrates retinal angiomatous proliferation and chorioretinal
      anastomosis of type 3 neovascularization.
AB  - PURPOSE: To report the OCT angiography findings of type 3 neovascularization.
      METHODS: Two cases (one each with retinal angiomatous proliferation and
      chorioretinal anastomosis) are reported, in which the conventional fundus
      fluorescein angiography and spectral-domain optical coherence tomography findings
      were inconclusive. RESULTS: OCT angiography demonstrated flow within the abnormal
      anastomotic network and delineated the extent of the lesion with respect to the
      retinal layers. CONCLUSION: OCT angiography enables a quick diagnosis of type 3
      neovascularization by demonstrating a supranormal flow within the lesion and
      delineates the lesion within different retinal layers.

PMID- 28766279
TI  - Spectrum of pachychoroid diseases.
AB  - PURPOSE: To perform a systematic review of the literature examining about the
      pachychoroid diseases spectrum. METHODS: A systematic literature search was
      performed using the Medline database. A total of four studies directly relevant
      to our search are reviewed here. RESULTS: A structurally and functionally intact
      choroid tissue is vitally important for the retina function. While central
      retinal artery is responsible to supply the 2/3, internal part of the retina,
      choroidal vein network is responsible for the remaining 1/3 external part.
      Abnormal choroidal blood flow leads to photoreceptor dysfunction and
      photoreceptor death in the retina. The methods used in the visualization of the
      choroid are ICG angiography (indocyanine green angiography), OCT (optic coherence
      tomography) devices which are often used nowadays, and its advanced version, OCT
      angiography. Pachychoroid diseases are a spectrum of 4 different disease groups.
      These groups are essentially the stages of the disease itself, as the increased
      severity in the previous group leads the patient to the next group of disease.
      CONCLUSION: The spectrum comprises the following 4 disease groups: Pachychoroid
      Pigment Epitheliopathy, Central Serous Chorioretinopathy, Pachychoroid
      Neovasculopathy, Polipoidal Choroidal Vasculopathy. Common Characteristics:
      Increased choroidal thickening, pathologically dilated veins in the Haller's
      layer (pachy-veins), thinning in Sattler's and choriocapilleris layers.

PMID- 28766280
TI  - Influence of glycosylated hemoglobin on the choroidal thickness.
AB  - PURPOSE: The aim of the study reported here was to assess the influence of serum
      HbA1c levels on foveal choroidal thickness in diabetic patients. METHODS: A total
      of 122 eyes from 122 patients who had type 2 DM were studied in this prospective,
      cross-sectional study. Patients were divided into three groups: 43 patients (43
      eyes) without diabetic retinopathy (NDR), 39 patients (39 eyes) with diabetic
      retinopathy and no macular edema (DR/ME-), 40 patients (40 eyes) with diabetic
      retinopathy and macular edema (DR/ME+). Central foveal thicknesses and subfoveal
      choroidal thicknesses were noted. Subfoveal choroidal thickness measurement was
      taken perpendicularly from the outer part of the retinal pigment epithelial layer
      to the line corresponding to the choroidal-scleral junction. Serum glycosylated
      hemoglobin (HbA1c) levels were evaluated. RESULTS: No significant differences in
      age, gender, pseudophakia were observed between the groups. There was no
      significant difference in HbA1c value among the three diabetic groups. Mean
      foveal choroidal thickness was 270.09 +/- 42.41 in NDR group, 243.18 +/- 30.21 in
      DR/ME- group and 250.90 +/- 40.06 in DR/ME+ group. Mean foveal choroidal
      thickness in NDR group was significantly different from DR/ME- group. There was
      no statistically significant difference between the other groups among foveal
      choroidal thicknesses. There was no correlation between HbA1c and foveal
      choroidal thickness. Multiple regression analyses of two diabetic retinopathy
      groups showed no significant correlation between foveal choroidal thickness and
      HbA1c and also no significant correlation between foveal choroidal thickness and
      duration of diabetes. CONCLUSIONS: Serum HbA1c levels were not correlated with
      foveal choroidal thickness. Choroidal thickness is effected by several factors as
      axial length, age and systemic diseases.

PMID- 28766282
TI  - Erratum to: Rene Dubos, tuberculosis, and the "ecological facets of virulence".

PMID- 28766281
TI  - Nebulized antibiotics in mechanically ventilated patients: a challenge for
      translational research from technology to clinical care.
AB  - Nebulized antibiotic therapy directly targets airways and lung parenchyma
      resulting in high local concentrations and potentially lower systemic toxicities.
      Experimental and clinical studies have provided evidence for elevated lung
      concentrations and rapid bacterial killing following the administration of
      nebulized antibiotics during mechanical ventilation. Delivery of high
      concentrations of antibiotics to infected lung regions is the key to achieving
      efficient nebulized antibiotic therapy. However, current non-standardized
      clinical practice, the difficulties with implementing optimal nebulization
      techniques and the lack of robust clinical data have limited its widespread
      adoption. The present review summarizes the techniques and clinical constraints
      for optimal delivery of nebulized antibiotics to lung parenchyma during invasive
      mechanical ventilation. Pulmonary pharmacokinetics and pharmacodynamics of
      nebulized antibiotic therapy to treat ventilator-associated pneumonia are
      discussed and put into perspective. Experimental and clinical pharmacokinetics
      and pharmacodynamics support the use of nebulized antibiotics. However, its
      clinical benefits compared to intravenous therapy remain to be proved. Future
      investigations should focus on continuous improvement of nebulization practices
      and techniques. Before expanding its clinical use, careful design of large phase
      III randomized trials implementing adequate therapeutic strategies in targeted
      populations is required to demonstrate the clinical effectiveness of nebulized
      antibiotics in terms of patient outcomes and reduction in the emergence of
      antibiotic resistance.

PMID- 28766285
TI  - Detection and Identification of Uncapped RNA by Ligation-Mediated Reverse
      Transcription Polymerase Chain Reaction.
AB  - The 5'-cap structure is an essential feature in eukaryotic mRNA required for mRNA
      stability and enhancement of translation. Ceratin transcripts are selectively
      silenced by decapping in the cytoplasm and later become translationally active
      again by acquiring the cap structure to regenerate translatable mRNAs.
      Identification of uncapped mRNA transcripts will reveal how gene expression is
      regulated by the mRNA recapping pathway. What follows is a sensitive method to
      detect and identify the uncapped mRNA from the cells. The technique consists of
      three parts: selective ligation of anchor RNA to the 5'-end of monophosphate RNA
      by double-strand RNA ligase, conversion of ligated RNA product into cDNA by
      reverse transcription, and amplification of a specific cDNA by polymerase chain
      reaction.

PMID- 28766283
TI  - Management of aorto-esophageal fistula secondary after thoracic endovascular
      aortic repair: a review of literature.
AB  - Aorto-esophageal fistula (AEF) is a rare and lethal entity, and the difficulty of
      making diagnosis of AEF is well-known. As promising results in the short-term
      effectiveness of thoracic endovascular aortic repair (TEVAR) promote its usage,
      the occurrence of AEF after TEVAR (post-TEVAR AEF) increases as one of the major
      complications. Therefore, we provide a review concerning the management strategy
      of post-TEVAR AEF. Although its representative symptom was reported as the triad
      of mid-thoracic pain and sentinel hematemesis followed by massive hematemesis,
      the symptom-free interval between sentinel hemorrhage and massive exsanguination
      is unpredictable. However, the physiological condition represents a surgical
      contraindication. Accordingly, early diagnosis is important, but either CT or
      esophago-gastro-duodenoscopy rarely depicts a typical image. The formation of
      post-TEVAR AEF might be associated with the infection of micro-organisms, which
      is uncontrollable with anti-biotic administration. The current first-line
      strategy is combination therapy as follows, (1) to control bleeding by TEVAR in
      the urgent phase, and (2) radical debridement and aortic/esophageal re
      construction in the semi-urgent phase. In view of the high mortality and
      morbidity rate, it is proposed that the choice in treatment strategies might be
      affected by patient's condition, size of the wall defects and the etiology of
      AEF. Practically, we should keep in mind the importance of making an early
      diagnosis and, once a suspicious symptom has occurred in a patient with a history
      of TEVAR, the existence of post-TEVAR AEF should be suspected. A prospective
      registry together with more developed technologies will be needed to establish a
      future strategy.

PMID- 28766286
TI  - Preparation of Splicing Competent Nuclear Extract from Mammalian Cells and In
      Vitro Pre-mRNA Splicing Assay.
AB  - The ability to perform in vitro splicing assays has paved the way for in-depth
      studies of the mechanisms and machinery involved in the process of splicing. The
      in vitro splicing assay is a valuable experimental approach that combines the
      complexity of the spliceosome and regulatory systems with the flexibility of
      performing endless splicing and alternative splicing reactions. Through the use
      of crude nuclear extract and radiolabeled pre-mRNA, spliced mRNAs can be
      visualized using autoradiography for downstream analysis. This chapter describes
      the necessary steps to perform an in vitro splicing reaction, including the
      generation of the key components necessary for the splicing reaction; nuclear
      extract.

PMID- 28766287
TI  - Single-Molecule Analysis of Pre-mRNA Splicing with Colocalization Single-Molecule
      Spectroscopy (CoSMoS).
AB  - Recent development of single-molecule techniques to study pre-mRNA splicing has
      provided insights into the dynamic nature of the spliceosome. Colocalization
      single-molecule spectroscopy (CoSMoS) allows following spliceosome assembly in
      real time at single-molecule resolution in the full complexity of cellular
      extracts. A detailed protocol of CoSMoS has been published previously (Anderson
      and Hoskins, Methods Mol Biol 1126:217-241, 2014). Here, we provide an update on
      the technical advances since the first CoSMoS studies including slide surface
      treatment, data processing, and representation. We describe various labeling
      strategies to generate RNA reporters with multiple dyes (or other moieties) at
      specific locations.

PMID- 28766288
TI  - In Vitro Modulation of Endogenous Alternative Splicing Using Splice-Switching
      Antisense Oligonucleotides.
AB  - Regulation of alternative splicing can be harnessed by antisense-based compounds
      to control gene expression. Antisense-mediated splicing interference has become a
      valuable molecular tool to modulate endogenous alternative splicing patterns, to
      correct cryptic or aberrant splicing, to reduce gene expression by triggering
      nonsense-mediated mRNA decay, and to activate intronic polyadenylation, both in
      vitro and in vivo. Here, we describe methods to induce and analyze the modulation
      of RNA processing, using modified splice-switching antisense oligonucleotides,
      such as phosphorodiamidate morpholino (PMO).

PMID- 28766289
TI  - Purification of mRNA Processing Complexes Using an RNA Affinity Approach.
AB  - Multiple mRNA processing steps, including splicing and 3' processing, take place
      in macromolecular complexes that contain many proteins and sometimes RNA
      molecules. A key challenge in the mRNA processing field has been to define the
      structure-function relationship of these sophisticated molecular machines. A
      prerequisite for addressing this challenge is to develop tools for purifying mRNA
      processing complexes in their native and intact forms that are suitable for
      functional and structural studies. Among many methods that have been developed,
      RNA affinity-based methods are most widely applied. In these methods, RNA
      molecules that are substrates to mRNA processing machineries are fused with an
      affinity tag, incubated with cellular extracts/lysates to allow for the assembly
      of mRNA processing complexes, and finally the assembled complexes are purified
      using RNA affinity tag. In this chapter, we will overview RNA affinity-based
      purification methods and describe in detail one such method, MS2-tagging, and its
      application in the purification of mRNA 3' processing complexes. Although these
      methods were originally developed for purifying mRNA processing complexes, they
      should be applicable to purification of other RNA-protein complexes as well.

PMID- 28766290
TI  - Polyadenylation Site-Based Analysis of Transcript Expression by 3'READS.
AB  - Deep sequencing of the 3' end region of poly(A)+ RNA identifies the cleavage and
      polyadenylation site (PAS) and measures transcript abundance. However, mispriming
      at internal A-rich regions by the oligo-dT oligo in reverse transcription can
      lead to falsely identified PASs. This problem can be resolved by direct ligation
      of an adapter to the 3' end of RNA. However, ligation-based methods are often
      inefficient. Here, we describe 3'READS+, an accurate and sensitive method for
      deep sequencing of the 3' end of poly(A)+ RNA. Through partial digestion by RNase
      H of the poly(A) tail bound to a locked nucleic acid (LNA)/DNA hybrid oligo, this
      method sequences an optimal number of terminal A's, which balances sequencing
      quality and accurate identification of PAS in A-rich regions. With efficient
      ligation steps, 3'READS+ is amenable to small amounts of input RNA. 3'READS+ can
      also be readily used as a cost-effective method for gene expression analysis.

PMID- 28766291
TI  - Comprehensive Identification of mRNA Polyadenylation Sites by PAPERCLIP.
AB  - We discuss a newly developed method to profile mRNA polyadenylation (pA) sites in
      an unbiased manner, PAPERCLIP (Poly(A) binding Protein-mediated mRNA 3'End
      Retrieval by CrossLinking ImmunoPrecipitation). Based on the well-established
      CLIP (crosslinking immunoprecipitation) technique, PAPERCLIP utilizes the poly(A)
      binding protein (PABP) as a biological filter to selectively retrieve mRNA 3' end
      fragments by immunoprecipitation from ultraviolet (UV) irradiated tissues or
      cultured cells. The mRNA fragments are subsequently extracted from the
      immunoprecipitated PABP:RNA complexes to generate a cDNA library, which goes
      through two rounds of purification before the final amplification by real-time
      polymerase chain reaction (PCR). The amplified cDNA library can then be read out
      by high-throughput sequencing to generate a transcriptomic profile and
      comprehensive alternative poly(A) (APA) site map from intact tissue or cultured
      cells.

PMID- 28766292
TI  - Microinjection and Fluorescence In Situ Hybridization Assay for Studying mRNA
      Export in Mammalian Cells.
AB  - Microinjection and Fluorescence in situ Hybridization (FISH) assay is a useful
      method for mRNA export studies, which can overcome the problems of traditional
      transfection in cells. Here, we describe the method of microinjection and FISH
      assay applied in investigation of mRNA export. By this method we can estimate the
      mRNA export kinetics, examining mRNA export in cells with low transfection
      efficiencies, and observing nuclear export of aberrant RNAs.

PMID- 28766293
TI  - Methods for the Detection of Adenosine-to-Inosine Editing Events in Cellular RNA.
AB  - Modification of RNA is essential for properly expressing the repertoire of RNA
      transcripts necessary for both cell type and developmental specific functions.
      RNA modifications serve to dynamically re-wire and fine-tune the genetic
      information carried by an invariable genome. One important type of RNA
      modification is RNA editing and the most common and well-studied type of RNA
      editing is the hydrolytic deamination of adenosine to inosine. Inosine is a
      biological mimic of guanosine; therefore, when RNA is reverse transcribed,
      inosine is recognized as guanosine by the reverse transcriptase and a cytidine is
      incorporated into the complementary DNA (cDNA) strand. During PCR amplification,
      guanosines pair with the newly incorporated cytidines. As a result, the adenosine
      to-inosine (A-to-I) editing events are recognized as adenosine to guanosine
      changes when comparing the sequences of the genomic DNA to the cDNA. This chapter
      describes the methods for extracting endogenous RNA for subsequent analyses of A
      to-I RNA editing using reverse transcriptase-based approaches. We discuss
      techniques for the detection of A-to-I RNA editing events in messenger RNA
      (mRNA), including analyzing editing levels at specific adenosines within the
      total pool of mRNA versus analyzing editing patterns that occur in individual
      transcripts and a method for detecting editing events across the entire
      transcriptome. The detection of RNA editing events and editing levels can be used
      to better understand normal biological processes and disease states.

PMID- 28766294
TI  - Using RNA-Seq to Discover Genetic Polymorphisms That Produce Hidden Splice
      Variants.
AB  - RNA-seq is a powerful and popular technology for studying posttranscriptional
      regulation of gene expression, such as alternative splicing. The first step in
      analyzing RNA-seq data is to map the sequenced reads back to the genome. However,
      commonly used RNA-seq aligners use the consensus splice site dinucleotide motifs
      to map reads across splice junctions. This can be deceiving due to genomic
      variants that create novel splice site dinucleotides, leaving the personal splice
      junction reads un-mapped to the reference genome. We developed and evaluated a
      method called RNA Personal Genome Alignment Analyzer (rPGA) to identify "hidden"
      splicing variations in personal transcriptomes, by mapping personal RNA-seq data
      to personal genomes. Our work demonstrates that the personal genome approach to
      RNA-seq read alignment enables the discovery of a large but previously unknown
      catalog of splicing variations in human populations.

PMID- 28766295
TI  - Inducible Expression of Eukaryotic Circular RNAs from Plasmids.
AB  - Thousands of eukaryotic protein-coding genes are noncanonically spliced to
      generate circular RNAs. Because they have covalently linked ends, circular RNAs
      are resistant to degradation by exonucleases and some accumulate to higher levels
      than their associated linear mRNAs. The functions of most circular RNAs are still
      unknown, but recent work has revealed key insights into how the pre-mRNA splicing
      machinery catalyzes backsplicing. Exons that circularize are often flanked by
      intronic repeat sequences that are complementary to one another, and backsplicing
      is triggered when these repeats base pair and bring the intervening splice sites
      into close proximity. Here, we describe how this knowledge has been translated
      into a simple plasmid-based method for ectopically expressing circular RNAs in
      eukaryotic cells. The sequence of interest is cloned into an artificial exon that
      is flanked by complementary intronic repeats. The plasmid is then transfected
      into cells, transcription is induced, and the cellular splicing machinery
      generates the desired circular RNA. Total RNA is isolated and the
      efficiency/specificity of circular RNA biogenesis is validated by Northern blot
      analysis. Beyond allowing overexpression of natural circular RNAs to define their
      functions, this approach can be used to produce designer RNA circles that are
      translated or bind specific cellular factors, such as microRNAs or proteins.

PMID- 28766296
TI  - Methods for Extraction of RNA, Proteins, or Protein Complexes from Subcellular
      Compartments of Eukaryotic Cells.
AB  - Eukaryotic organelles or subcellular compartments can be selectively isolated
      based on their physical density and their stability in the presence of nonionic
      detergents. This chapter describes a protocol for the preparation of cytoplasm,
      nucleoplasm, and chromatin, in addition to isolation of RNA and proteins from
      these fractions. Proteins and protein complexes stably associated with chromatin
      and other high molecular weight nuclear components can be extracted under non
      denaturing conditions by enzymatic digestion of RNA and DNA. The chapter also
      includes a detailed extraction protocol from highly purified nuclei.

PMID- 28766297
TI  - Isolation of Newly Transcribed RNA Using the Metabolic Label 4-Thiouridine.
AB  - Isolation of newly transcribed RNA is an invaluable approach that can be used to
      study the dynamic life of RNA in cellulo. Traditional methods of whole-cell RNA
      extraction limit subsequent gene expression analyses to the steady-state levels
      of RNA abundance, which often masks changes in RNA synthesis and processing. This
      chapter describes a methodology with low cytotoxicity that permits the labeling
      and isolation of nascent pre-mRNA in cell culture. The resulting isolate is
      suitable for use in a series of downstream applications aimed at studying changes
      in RNA synthesis, processing, or stability.

PMID- 28766298
TI  - Robust, Cost-Effective Profiling of RNA Binding Protein Targets with Single-end
      Enhanced Crosslinking and Immunoprecipitation (seCLIP).
AB  - Profiling of RNA binding protein targets in vivo provides critical insights into
      the mechanistic roles they play in regulating RNA processing. The enhanced
      crosslinking and immunoprecipitation (eCLIP) methodology provides a framework for
      robust, reproducible identification of transcriptome-wide protein-RNA
      interactions, with dramatically improved efficiency over previous methods. Here
      we provide a step-by-step description of the eCLIP method, along with insights
      into optimal performance of critical steps in the protocol. In particular, we
      describe improvements to the adaptor strategy that enables single-end enhanced
      CLIP (seCLIP), which removes the requirement for paired-end sequencing of eCLIP
      libraries. Further, we describe the observation of contaminating RNA present in
      standard nitrocellulose membrane suppliers, and present options with
      significantly reduced contamination for sensitive applications. These notes
      further refine the eCLIP methodology, simplifying robust RNA binding protein
      studies for all users.

PMID- 28766301
TI  - Genome-Wide RNAi Screens for RNA Processing Events in Drosophila melanogaster S2
      Cells.
AB  - Over the past 10 years, the design and application of genome-wide screening (GWS)
      has improved to the point that it can now be done at level of the individual
      laboratory. The advantages of GWSs compared to classical genetic screens include:
      immediate identification of a positive scoring gene, relatively short period of
      time necessary to conduct the screen (as little as 1 week), cell lines do not
      present developmental needs for gene expression that an organism normally would,
      and validation/confirmation of results is straightforward. Here, we describe a
      general protocol for GWS to be conducted in Drosophila melanogaster S2 cells. We
      provide specific details on what type of experiments must be done before
      initiating a screen, the materials that are required to conduct a screen, and
      make suggestions on methods to carry out secondary screening and counter
      screening once the initial GWS is complete. Multiple considerations are also
      raised that focus on how to anticipate false positives/negatives and how to
      minimize their occurrence through intelligent design. Finally, we provide
      specific examples of data that our group has gathered from published genome-wide
      screens in order to exemplify how "hits" are scored and confirmed.

PMID- 28766299
TI  - Purification of Transcript-Specific mRNP Complexes Formed In Vivo from
      Saccharomyces cerevisiae.
AB  - RNA binding proteins play critical roles in shaping the complex life cycle of
      cellular transcripts. For most RNAs, the association with a distinct complement
      of proteins serves to orchestrate its unique pattern of maturation, localization,
      translation, and stability. A key aspect to understanding how transcripts are
      differentially regulated lies, therefore, in the ability to identify the
      particular repertoire of protein binding partners associated with an individual
      transcript. We describe here an optimized experimental procedure for purifying a
      single mRNA population from yeast cells for the characterization of transcript
      specific mRNA-protein complexes (mRNPs) as they exist in vivo. Chemical cross
      linking is used to trap native mRNPs and facilitate the co-purification of
      protein complexes associated with an individual transcript population that is
      captured under stringent conditions from cell lysates through hybridization to
      complementary DNA oligonucleotides. The resulting mRNP is highly enriched and
      largely devoid of non-target transcripts, and can be used for a number of
      downstream analyses including protein identification by mass spectrometry.

PMID- 28766300
TI  - A Cell-Based High-Throughput Method for Identifying Modulators of Alternative
      Splicing.
AB  - Alternative splicing, a key regulatory process of gene expression, is controlled
      by trans-acting factors that recognize cis-elements in premature RNA transcripts
      to affect spliceosome assembly and splice site choices. Extracellular stimuli and
      signaling cascades can converge on RNA binding splicing regulators to affect
      alternative splicing. Defects in splicing regulation have been associated with
      various human diseases, and modification of disease-causing splicing events
      presents great therapeutic promise. Determining splicing regulators and/or
      upstream modulators has been difficult with low throughput, low sensitivity, and
      low specificity. IRAS (identifying regulators of alternative splicing) is a novel
      cell-based high-throughput screening strategy designed specifically to address
      these challenges and has achieved high throughput, high sensitivity, and high
      specificity. Here, we describe the IRAS method in detail with a pair of dual
      fluorescence minigene reporters that produces GFP and RFP fluorescent signals to
      assay the two spliced isoforms exclusively. These two complementary mini-gene
      reporters alter GFP/RFP output ratios in the opposite direction in response to
      only a true splicing change. False positives from a signal screen do not
      stimulate opposite changes in GFP/RFP ratios. The reporter pair in conjunction
      with robotic liquid handlers and arrayed libraries allows IRAS to screen for both
      positive and negative splicing regulators with high sensitivity and specificity
      in a high-throughput manner.

PMID- 28766302
TI  - Assaying RNA Structure Inside Living Cells with SHAPE.
AB  - RNA molecules have emerged as key players in nearly every facet of gene
      regulation. Such functions are governed by RNA's unique ability to fold into
      intricate secondary and tertiary structures. In order to understand, on the
      molecular level, how such structures from several chemical and enzymatic methods
      have been developed. One such method is RNA Selective Hydroxyl Acylation analyzed
      by Primer Extension, or SHAPE. SHAPE has emerged as a premier method of measuring
      RNA structure, with recent developments extending SHAPE into living cells. Here,
      we describe the use of SHAPE for measuring RNA structure inside living cells.

PMID- 28766303
TI  - Impact of absence of critical respiratory rate change on oxygen desaturation
      following tracheal extubation after general anaesthesia: a propensity score
      matched analysis.
AB  - BACKGROUND: It has been suggested that oxygen desaturation may be paradoxically
      related to the absence of an abnormal respiratory rate (RR) during acoustic
      respiratory rate (RRa) monitoring in a postoperative setting. We retrospectively
      compared the incidence of desaruration in patients without an abnormal RR with
      that in patients with an abnormal RR using propensity scorer matching. We also
      explored the factors contributing to oxygen desaturation without an RR monitoring
      alert. METHODS: We used <= 8 h postoperative data of the first 935 patients.
      Outcomes of patients with and without critical RR changes (RR > 30 or < 8 beats
      per min for > 2 min) (critical RR change vs. noncritical RR change) were first
      compared according to oxygen desaturation levels (SpO2< 90% for > 10 s).
      Multivariate analysis was used to determine oxygen desaturation-associated
      explanatory factors. RESULTS: Propensity score matching yielded 259 patients
      without critical RR changes and 259 patients with critical RR changes,
      respectively. Oxygen desaturation rates were higher in patients without critical
      RR changes [noncritical RR change vs. critical RR change: 39/220 (15.1%) vs.
      16/243 (6.2%)]. An odds ratio and 95% CI for the noncritical RR change was 2.56
      (1.38-4.55, P = 0.002). A critical change in the RRa was not observed in 576
      patients; of these, oxygen desaturation was observed in 76 (13.2%) patients.
      Surgery duration (OR, 1.018 per 10 min increase; 95% CI, 1.002 to 1.035) was
      independently associated with oxygen desaturation without critical RR change.
      CONCLUSION: Postoperative oxygen desaturation paradoxically occurred more
      frequently in patients without critical RR changes, whose RR was monitored by the
      RRa under oxygen therapy. The duration of surgery may explain the possibility of
      postoperative oxygen desaturation without an RRa device alert.

PMID- 28766304
TI  - Benefits of ultrasound-guided transversus abdominis plane block for open
      appendectomy in children.
AB  - BACKGROUND: One of the most frequently performed emergency surgical procedures in
      children is an appendectomy. The aim of this study was to determine the benefits
      of supplementing standard, general anaesthesia with the ultrasound-guided right
      TAP block. METHODS: We analyzed the medical records of 90 children of both sexes,
      aged 4-16 years with a body mass of 16-78 kg who underwent general anaesthesia
      for open appendectomy. Sixty-two individuals were anaesthetized using the
      standard method, while 28 patients had an additional right-sided TAP block under
      ultrasound guidance. Subsequently these groups were divided into 2 subgroups:
      children under 8 years and those older. We evaluated the total consumption of
      opioids, intraoperative fentanyl requirement, the amount of non-opioid analgesic
      and antiemetic drugs used during the whole hospitalization, time to recovery of
      digestive track function and length of hospital stay. RESULTS: TAP block
      performed under USG guidance reduced the overall consumption of opioids (0.36 vs.
      0.42 mg kg-1, P = 0.048), significantly shortened time of fasting after the
      surgery (17 vs. 29 hours, P = 0.003) as well as reduced the need for antiemetic
      drugs: ondansetron were used only in 21.4% of children in the group with TAP
      block vs. 38.7% of children with standard protocol. Additionally, we noted that
      the application of the TAP block shortened the length of hospitalization (3 vs. 4
      days, P = 0.045). CONCLUSION: The application of the TAP block, as a
      supplementary treatment to standard general anaesthesia for open appendectomy in
      children is a valuable component of multimodal analgesia, which might improve the
      quality of life of the patient and shorten the length of hospitalization.

PMID- 28766305
TI  - Aerosplenism in the intensive care unit.

PMID- 28766307
TI  - Efficient [Cu(NHC)]-Catalyzed Multicomponent Synthesis of Pyrroles.
AB  - Efficient [Cu(NHC)]-catalyzed syntheses of pyrroles via two and three-component
      coupling methods are described. Various 1,2-, 1,2,3-, 1,2,3,5- and fully
      substituted pyrroles were readily accessible through a suitable choice of ketone,
      primary amine and diol in a three-component reaction. The N-unsubstituted pyrrole
      formation is also feasible through a two-component reaction involving a beta
      amino alcohol and a ketone.

PMID- 28766306
TI  - Interpretation of Brain CT Scans in the Field by Critical Care Physicians in a
      Mobile Stroke Unit.
AB  - BACKGROUND AND PURPOSE: In acute stroke, thromboembolism or spontaneous
      hemorrhage abruptly reduces blood flow to a part of the brain. To limit necrosis,
      rapid radiological identification of the pathological mechanism must be conducted
      to allow the initiation of targeted treatment. The aim of the Norwegian Acute
      Stroke Prehospital Project is to determine if anesthesiologists, trained in
      prehospital critical care, may accurately assess cerebral computed tomography
      (CT) scans in a mobile stroke unit (MSU). METHODS: In this pilot study, 13
      anesthesiologists assessed unselected acute stroke patients with a cerebral CT
      scan in an MSU. The scans were simultaneously available by teleradiology at the
      receiving hospital and the on-call radiologist. CT scan interpretation was
      focused on the radiological diagnosis of acute stroke and contraindications for
      thrombolysis. The aim of this study was to find inter-rater agreement between the
      pre- and in-hospital radiological assessments. A neuroradiologist evaluated all
      CT scans retrospectively. Statistical analysis of inter-rater agreement was
      analyzed with Cohen's kappa. RESULTS: Fifty-one cerebral CT scans from the MSU
      were included. Inter-rater agreement between prehospital anesthesiologists and
      the in-hospital on-call radiologists was excellent in finding radiological
      selection for thrombolysis (kappa .87). Prehospital CT scans were conducted in
      median 10 minutes (7 and 14 minutes) in the MSU, and median 39 minutes (31 and 48
      minutes) before arrival at the receiving hospital. CONCLUSION: This pilot study
      shows that anesthesiologists trained in prehospital critical care may effectively
      assess cerebral CT scans in an MSU, and determine if there are radiological
      contraindications for thrombolysis.

PMID- 28766308
TI  - CsPb2 Br5 Single Crystals: Synthesis and Characterization.
AB  - CsPb2 Br5 is a ternary halogen-plumbate material with close characteristics to
      the well-reported halide perovskites. Owing to its unconventional two-dimensional
      structure, CsPb2 Br5 is being looked at broadly for potential applications in
      optoelectronics. CsPb2 Br5 investigations are currently limited to nanostructures
      and powder forms of the material, which present unclear and conflicting optical
      properties. In this study, we present the synthesis and characterization of CsPb2
      Br5 bulk single crystals, which enabled us to finally clarify the material's
      optical features. Our CsPb2 Br5 crystal has a two-dimensional structure with Pb2
      Br5- layers spaced by Cs+ cations, and exhibits approximately 3.1 eV indirect
      band gap with no emission in the visible spectrum.

PMID- 28766310
TI  - Tropical Medicine & International Health.

PMID- 28766309
TI  - The psychological impact of prostate biopsy: Prevalence and predictors of
      procedure-related distress.
AB  - OBJECTIVE: Many men undergo prostate biopsies each year. Most data on
      consequences of prostate biopsy for men pertain to physical after-effects and/or
      come from clinical trial populations. We quantified prevalence of, and identified
      factors associated with, procedure-related distress in men having prostate
      biopsies in routine clinical practice. METHODS: Men who had undergone prostate
      biopsy for follow-up of a raised prostate specific antigen test result and/or
      abnormal digital rectal examination in 6 centres in Ireland completed
      questionnaires. Biopsy-related psychological distress was measured using the
      Impact of Event Scale. An Impact of Event Scale score >= 9 was considered
      significant biopsy-related distress. Logistic regression was used to identify
      predictors of significant distress. RESULTS: Three hundred thirty-five men
      completed questionnaires. Overall, 49% had significant biopsy-related distress;
      this was higher in men whose biopsy result indicated cancer (59%) and those who
      did not have a definitive result (54%) than those with a negative result (35%; P
      < .001). In multivariable analyses, the odds of significant distress were 3 times
      higher in men with cancer (OR = 3.33, 95% CI, 1.83-6.04) and more than twice as
      high in men without a definitive result (OR = 2.61, 95% CI, 1.43-4.78) compared
      to men with a negative result. Men with intermediate (OR = 3.19, 95% CI, 1.85
      5.53) or high (OR = 7.10, 95% CI, 3.45-14.57) health anxiety (propensity to worry
      about one's health) also had significantly increased odds of biopsy-related
      distress. CONCLUSIONS: Significant distress is common after prostatic biopsy.
      Some men, including those who are highly health anxious and those awaiting
      definitive results, may benefit from additional support around the time of and/or
      following prostate biopsy.

PMID- 28766311
TI  - Enantiospecific Elongation of Cationic Helicenes by Electrophilic
      Functionalization at Terminal Ends.
AB  - A strategy for late-stage electrophilic functionalizations of cationic helicenes
      is exposed. Thanks to strongly acidic conditions that permit reversible
      electrophilic substitutions, regioselective acylations, sulfonylations, or
      alkylations occur at the extremity(ies) of the helical cores. Extended [5] or
      [6]helicenes can then be generated from cationic [4]helicenes in successive one
      pot elongation processes. Retention of configuration and excellent
      enantiospecificity (up to 99 %) are observed for the helicene growth in the
      enantiopure series.

PMID- 28766312
TI  - Comparison of marginal bone loss and implant success between axial and tilted
      implants in maxillary All-on-4 treatment concept rehabilitations after 5 years of
      follow-up.
AB  - BACKGROUND: There is need for more scientific and clinical information on longer
      term outcomes of tilted implants compared to implants inserted in an axial
      position. PURPOSE: Comparison of marginal bone loss and implant success after a 5
      year follow-up between axial and tilted implants inserted for full-arch maxillary
      rehabilitation. MATERIAL AND METHODS: The retrospective clinical study included
      891 patients with 3564 maxillary implants rehabilitated according to the All-on-4
      treatment concept. The follow-up time was 5 years. Linear mixed-effect models
      were performed to analyze the influence of implant orientation (axial/tilted) on
      marginal bone loss and binary logistic regression to assess the effect of patient
      characteristics on occurrence of marginal bone loss >2.8 mm. Only those patients
      with measurements of at least one axial and one tilted implant available were
      analyzed. This resulted in a data set of 2379 implants (1201 axial, 1178 tilted)
      in 626 patients (=reduced data set). RESULTS: Axial and tilted implants showed
      comparable mean marginal bone losses of 1.14 +/- 0.71 and 1.19 +/- 0.82 mm,
      respectively. Mixed model analysis indicated that marginal bone loss levels at 5
      years follow up was not significantly affected by the orientation (axial/tilted)
      of the implants in the maxillary bone. Smoking and female gender were associated
      with marginal bone loss >2.8 mm in a logistic regression analysis. Five-year
      implant success rates were 96%. The occurrence of implant failure showed to be
      statistically independent from orientation. CONCLUSIONS: Within the limitations
      of this study and considering a follow-up time of 5 years, it can be concluded
      that tilted implants behave similarly with regards to marginal bone loss and
      implant success in comparison to axial implants in full-arch rehabilitation of
      the maxilla. Longer-term outcomes (10 years +) are needed to verify this result.

PMID- 28766313
TI  - Interventions for emergency contraception.
AB  - BACKGROUND: Emergency contraception (EC) is using a drug or copper intrauterine
      device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse.
      Several interventions are available for EC. Information on the comparative
      effectiveness, safety and convenience of these methods is crucial for
      reproductive healthcare providers and the women they serve. This is an update of
      a review previously published in 2009 and 2012. OBJECTIVES: To determine which EC
      method following unprotected intercourse is the most effective, safe and
      convenient to prevent pregnancy. SEARCH METHODS: In February 2017 we searched
      CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese
      biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human
      Reproduction (HRP) emergency contraception database. We also searched ICTRP and
      ClinicalTrials.gov as well as contacting content experts and pharmaceutical
      companies, and searching reference lists of appropriate papers. SELECTION
      CRITERIA: Randomised controlled trials including women attending services for EC
      following a single act of unprotected intercourse were eligible. DATA COLLECTION
      AND ANALYSIS: We used standard methodological procedures recommended by Cochrane.
      The primary review outcome was observed number of pregnancies. Side effects and
      changes of menses were secondary outcomes. MAIN RESULTS: We included 115 trials
      with 60,479 women in this review. The quality of the evidence for the primary
      outcome ranged from moderate to high, and for other outcomes ranged from very low
      to high. The main limitations were risk of bias (associated with poor reporting
      of methods), imprecision and inconsistency. Comparative effectiveness of
      different emergency contraceptive pills (ECP)Levonorgestrel was associated with
      fewer pregnancies than Yuzpe (estradiol-levonorgestrel combination) (RR 0.57, 95%
      CI 0.39 to 0.84, 6 RCTs, n = 4750, I2 = 23%, high-quality evidence). This
      suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women
      per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24
      women per 1000.Mifepristone (all doses) was associated with fewer pregnancies
      than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I2 = 0%, high-quality
      evidence). This suggests that if the chance of pregnancy following Yuzpe is
      assumed to be 25 women per 1000 women, the chance following mifepristone would be
      between 1 and 10 women per 1000.Both low-dose mifepristone (less than 25 mg) and
      mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer
      pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752,
      I2 = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052,
      I2 = 0%, moderate-quality evidence; respectively). This suggests that if the
      chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000,
      the chance of pregnancy following low-dose mifepristone would be between 10 and
      20 women per 1000; and that if the chance of pregnancy following levonorgestrel
      is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose
      mifepristone would be between 16 and 29 women per 1000.Ulipristal acetate (UPA)
      was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35
      to 0.99, 2 RCTs, n = 3448, I2 = 0%, high-quality evidence). Comparative
      effectiveness of different ECP dosesIt was unclear whether there was any
      difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the
      standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33,
      3 RCTs, n = 6653, I2 = 0%, moderate-quality evidence).Mid-dose mifepristone was
      associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI
      0.55 to 0.97, 25 RCTs, n = 11,914, I2 = 0%, high-quality evidence). Comparative
      effectiveness of Cu-IUD versus mifepristoneThere was no conclusive evidence of a
      difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33,
      95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence). Adverse
      effectsNausea and vomiting were the main adverse effects associated with
      emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95%
      CI 0.53 to 0.76, 3 RCTs, n = 2186 , I2 = 59%, moderate-quality evidence) or
      vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I2 = 0%, high-quality
      evidence) associated with mifepristone than with Yuzpe. levonorgestrel is
      probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6
      RCTs, n = 4750, I2 = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95%
      CI 0.24 to 0.35, 5 RCTs, n = 3640, I2 = 78%, moderate-quality evidence) than
      Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe
      users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA
      users were more likely than levonorgestrel users to have resumption of
      menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n =
      3593, I2 = 0%, high-quality evidence). Menstrual delay was more common with
      mifepristone than with any other intervention and appeared to be dose-related. Cu
      IUD may be associated with higher risks of abdominal pain than mifepristone (18
      events in 95 women using Cu-IUD versus no events in 190 women using mifepristone,
      low-quality evidence). AUTHORS' CONCLUSIONS: Levonorgestrel and mid-dose
      mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid
      dose (25 mg to 50 mg) and low-dose mifepristone(less than 25 mg) were probably
      more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25
      mg) was less effective than mid-dose mifepristone. UPA was more effective than
      levonorgestrel.Levonorgestrel users had fewer side effects than Yuzpe users, and
      appeared to be more likely to have a menstrual return before the expected date.
      UPA users were probably more likely to have a menstrual return after the expected
      date. Menstrual delay was probably the main adverse effect of mifepristone and
      seemed to be dose-related. Cu-IUD may be associated with higher risks of
      abdominal pain than ECPs.

PMID- 28766314
TI  - Sex Differences in Contraception Non-Use Among Urban Adolescents: Risk Factors
      for Unintended Pregnancy.
AB  - BACKGROUND: Contraception non-use among sexually active adolescents is a major
      cause of unintended pregnancy (UP). METHODS: In this cross-sectional study we
      sought to identify overall and sex-specific correlates of contraception non-use
      using the 2015 Philadelphia Youth Risk Behavior Survey (YRBS) (N = 9540).
      Multivariate regression models were used to examine mental health, sexual
      activity, substance use, and violence indicators on reported contraception non
      use among sexually active youth. RESULTS: Marijuana use among boys and girls was
      a statistically significant risk factor for contraception non-use. Availability
      of illegal drugs on school property in the past year was also significantly
      related to contraception non-use among boys. CONCLUSIONS: These results may
      inform overall and sex-specific adolescent programs to promote consistent
      contraception use among urban youth within school-based communities.

PMID- 28766315
TI  - Physical Activity and School Absenteeism Due to Illness in Adolescents.
AB  - BACKGROUND: Knowledge about the beneficial role of physical activity (PA) for
      health and school performance is growing. Studies investigating the link between
      PA and school absenteeism due to illness are lacking. Therefore, we investigated
      associations between habitual PA and school absenteeism due to illness in
      adolescents and explored whether mental health and cardiovascular fitness
      mediated this association. METHODS: We studied 328 students in grades 7 and 9
      (mean age 13.8 years; 49% boys). The PA was measured objectively by an
      ActivPAL3TM accelerometer attached on the thigh during 1 full week (24
      hours/day). Depressive symptoms and self-esteem were self-reported by the Center
      for Epidemiologic Studies Depression Scale (CES-D) and Rosenberg Self-Esteem
      Scale, respectively, and included as a proxy for mental health in the analyses.
      Cardiovascular fitness was measured by the 20-m shuttle-run test. School
      absenteeism due to illness data was provided by the school administration.
      RESULTS: The PA was not significantly associated with school absenteeism, though
      there was an indirect association between PA and school absenteeism by
      cardiovascular fitness. CONCLUSIONS: Cardiovascular fitness mediates the
      association between PA and school absenteeism due to illness. Thus,
      cardiovascular fitness of students should be improved to reduce school
      absenteeism due to illness.

PMID- 28766316
TI  - School-Based Outcomes Among Youth With Incarcerated Parents: Differences by
      School Setting.
AB  - BACKGROUND: Parental incarceration impacts millions of children in the United
      States and has important consequences for youths' adjustment and school-based
      outcomes. METHODS: Using data from a survey of youth behavior in one large
      Midwestern state, we examined the effect of both present and past parental
      incarceration on school-based outcomes, across 3 school settings (public schools,
      alternative learning centers, and juvenile correctional facilities). RESULTS:
      Parental incarceration was significantly associated with students' poor school
      based outcomes; however, these effects varied markedly by school setting. Among
      youth in public schools, parental incarceration was consistently associated with
      poor school outcomes. There were mixed effects among youth in alternative
      learning centers and no significant effects among youth in juvenile correctional
      facilities. CONCLUSIONS: The study adds to a body of literature demonstrating the
      negative effects of parental incarceration on youth's school-based outcomes for
      youth in public schools; however, findings were mixed for youth in alternative
      learning centers and juvenile correctional facilities. Implications for future
      research and school practitioners are discussed.

PMID- 28766317
TI  - Chronic Childhood Trauma, Mental Health, Academic Achievement, and School-Based
      Health Center Mental Health Services.
AB  - BACKGROUND: Children and adolescents exposed to chronic trauma have a greater
      risk for mental health disorders and school failure. Children and adolescents of
      minority racial/ethnic groups and those living in poverty are at greater risk of
      exposure to trauma and less likely to have access to mental health services.
      School-based health centers (SBHCs) may be one strategy to decrease health
      disparities. METHODS: Empirical studies between 2003 and 2013 of US pediatric
      populations and of US SBHCs were included if research was related to childhood
      trauma's effects, mental health care disparities, SBHC mental health services, or
      SBHC impact on academic achievement. RESULTS: Eight studies show a significant
      risk of mental health disorders and poor academic achievement when exposed to
      childhood trauma. Seven studies found significant disparities in pediatric mental
      health care in the US. Nine studies reviewed SBHC mental health service access,
      utilization, quality, funding, and impact on school achievement. CONCLUSION:
      Exposure to chronic childhood trauma negatively impacts school achievement when
      mediated by mental health disorders. Disparities are common in pediatric mental
      health care in the United States. SBHC mental health services have some showed
      evidence of their ability to reduce, though not eradicate, mental health care
      disparities.

PMID- 28766318
TI  - Teen Dating Violence Victimization Among High School Students: A Multilevel
      Analysis of School-Level Risk Factors.
AB  - BACKGROUND: Much etiologic research has focused on individual-level risk factors
      for teen dating violence (TDV); therefore, less is known about school-level and
      neighborhood-level risk factors. We examined the association between alcohol
      outlet density around high schools and TDV victimization and the association
      between markers of physical disorder around schools and TDV victimization among
      adolescents. METHODS: Data come from high school students participating in the
      Maryland Safe and Supportive Schools Initiative. Alcohol outlet density was
      calculated using walking distance buffers around schools. An observational tool
      was used to assess indicators of physical disorder on school property (eg,
      alcohol and drug paraphernalia). Hierarchical linear modeling was used to
      identify student- and school-level predictors associated with TDV victimization.
      RESULTS: Overall, 11% of students reported experiencing physical TDV and 11%
      reported experiencing psychological TDV over the past year. Recent alcohol use
      was a risk factor for TDV victimization for both sexes, whereas feeling safe at
      school was protective against TDV victimization for both sexes. Greater alcohol
      outlet density was associated with decreased TDV victimization for males,
      however, it was nonsignificant for females. Physical disorder around schools was
      not associated with TDV victimization for either sex. CONCLUSION: Although the
      school-level predictors were not associated with TDV victimization, alcohol use
      and perceptions of safety at school were significantly associated with TDV
      victimization. Prevention efforts to address alcohol use may affect TDV
      victimization.

PMID- 28766319
TI  - Acceptability of School-Based Health Centers for Human Papillomavirus Vaccination
      Visits: A Mixed-Methods Study.
AB  - BACKGROUND: Countries with high human papillomavirus (HPV) vaccination rates have
      achieved this success largely through school-based vaccination. Using school
      based health centers (SBHCs) in the United States, where HPV vaccine remains
      underutilized, could improve uptake. In this mixed-methods study, we examined
      acceptability, facilitators, and barriers of HPV vaccination visits at SBHCs from
      the perspectives of adolescents and parents. METHODS: We conducted qualitative
      interviews and structured surveys with adolescents and parents recruited from an
      urban, hospital-based clinic. Interviews with parents (N = 20) and adolescents (N
      = 20) were audio-recorded and transcribed for analysis using an iterative
      thematic approach. Quantitative measures for a survey administered to parents (N
      = 131) were derived from the qualitative findings. Survey results were analyzed
      by chi-square tests. RESULTS: Many participants expressed favorable opinions of
      HPV vaccination at SBHCs in qualitative interviews. Facilitators included
      convenience, ease of scheduling, and not missing work or school. However,
      barriers were noted including concerns about obtaining care outside the medical
      home, fragmentation of medical records, and negative perceptions about SBHCs.
      Quantitative findings revealed that a higher proportion of parents with
      experience using SBHCs were willing to use a middle school (59.5%) or high school
      (80.5%) SBHC for HPV vaccinations compared with those who had not used SBHCs (p <
      .05 for both comparisons). CONCLUSIONS: HPV vaccination visits at SBHCs were
      acceptable, and SBHC users expressed more favorable attitudes. Barriers to HPV
      vaccination at SBHCs can be addressed through more education about SBHCs' role,
      and improvement of systems to coordinate care.

PMID- 28766320
TI  - Nutrition Education and Body Mass Index in Grades K-12: A Systematic Review.
AB  - BACKGROUND: Overweight and obese body mass index (BMI) status affects an
      increasing number of children in the United States. The school setting has been
      identified as a focus area to implement obesity prevention programs. METHODS: A
      database search of PubMed, Education Search Complete, and Cumulative Index to
      Nursing and Allied Health Literature (CINAHL) was conducted for peer-reviewed
      articles published between January 2005 and December 2015 pertaining to programs
      offered in the school setting to grades K-12 in the United States with a
      nutrition education component and measured BMI percentile or BMI z-score as an
      outcome. RESULTS: Seven studies focused on elementary (K-5) populations and 2
      studies focused on grades 6-8. Among the 9 identified studies, those with long
      term (greater than 1 year) implementation showed more pronounced results with
      positive impact on reducing overweight/obese BMI measures. CONCLUSIONS: This set
      of studies suggests that long-term nutrition education delivered in the school
      setting can provide children with tools to attain a healthy weight status.
      Additional studies examining participants' BMI status years after the initial
      study, and studies examining programs in grades 9-12 are needed to determine the
      most effective delivery time and methods.

PMID- 28766321
TI  - Flavored Milk Consumers Drank More Milk and Had a Higher Prevalence of Meeting
      Calcium Recommendation Than Nonconsumers.
AB  - BACKGROUND: Some schools are removing flavored milk because of the perception
      that it negatively impacts children's overall diet. This study assessed the
      contribution of flavored milk to their diets. METHODS: Individual usual intakes
      (IUI) were calculated from 24-hour dietary recalls of children 2-18 years (N =
      20,329) participating in National Health and Nutrition Examination Survey
      (NHANES) 2001-2012. IUI of >0.25 cup equivalent of flavored dairy milk defined
      consumers (N = 3564; 56% boys). Covariate-adjusted regression analyses using
      appropriate sample weights were calculated. Estimated Average Requirements (EAR)
      and Adequate Intakes (AI) determined the relation to dietary recommendations.
      Consumers were compared to nonconsumers (p <= .001). RESULTS: Flavored milk
      consumers consumed more milk. Consumers aged 2-3 years had higher mean added
      sugars intakes. Consumers aged between 2-3 and 9-13 years had a higher saturated
      fat (SFA) intake. Consumers aged 14-18 years had higher percent energy from SFA.
      Consumers had a lower mean percentage of children meeting AI for fiber and a
      higher percentage meeting the EAR for calcium. Consumers aged 4-8 and 9-13 years
      had a higher mean percentage of children meeting the EAR for magnesium.
      CONCLUSIONS: Consumption of flavored milk has the potential to increase milk
      consumption and reduce the percentage of children below the EAR for calcium; the
      percentage meeting AI for fiber was lower.

PMID- 28766322
TI  - Concussion Knowledge and Reporting Behavior Differences Between High School
      Athletes at Urban and Suburban High Schools.
AB  - BACKGROUND: We determined differences in knowledge of concussion and reporting
      behaviors of high school athletes attending urban and suburban high schools, and
      whether a relationship exists between underreporting and access to an athletic
      trainer in urban schools. METHODS: High school athletes (N = 715) from 14 high
      schools completed a validated knowledge of concussion survey consisting of 83
      questions. The independent variable was school type (urban/suburban). We examined
      the proportion of athletes who correctly identified signs and symptoms of
      concussion, knowledge of concussion and reasons why high school athletes would
      not disclose a potential concussive injury across school classification. Data
      were analyzed using descriptive, non-parametric, and inferential statistics.
      RESULTS: Athletes attending urban schools have less concussion knowledge than
      athletes attending suburban schools (p < .01). Athletes attending urban schools
      without an athletic trainer have less knowledge than urban athletes at schools
      with an athletic trainer (p < .01) There was no significant relationship between
      reporting percentage and school type (p = .73); however, significant
      relationships exist between AT access at urban schools and 10 reasons for not
      reporting. CONCLUSION: Concussion education efforts cannot be homogeneous in all
      communities. Education interventions must reflect the needs of each community.

PMID- 28766323
TI  - Subcopula-based measure of asymmetric association for contingency tables.
AB  - For the analysis of a two-way contingency table, a new asymmetric association
      measure is developed. The proposed method uses the subcopula-based regression
      between the discrete variables to measure the asymmetric predictive powers of the
      variables of interest. Unlike the existing measures of asymmetric association,
      the subcopula-based measure is insensitive to the number of categories in a
      variable, and thus, the magnitude of the proposed measure can be interpreted as
      the degree of asymmetric association in the contingency table. The theoretical
      properties of the proposed subcopula-based asymmetric association measure are
      investigated. We illustrate the performance and advantages of the proposed
      measure using simulation studies and real data examples.

PMID- 28766324
TI  - Resting-state fMRI and social cognition: An opportunity to connect.
AB  - Many psychiatric disorders are characterized by altered social cognition. The
      importance of social cognition has previously been recognized by the National
      Institute of Mental Health Research Domain Criteria project, in which it features
      as a core domain. Social task-based functional magnetic resonance imaging (fMRI)
      currently offers the most direct insight into how the brain processes social
      information; however, resting-state fMRI may be just as important in
      understanding the biology and network nature of social processing. Resting-state
      fMRI allows researchers to investigate the functional relationships between brain
      regions in a neutral state: so-called resting functional connectivity (RFC).
      There is evidence that RFC is predictive of how the brain processes information
      during social tasks. This is important because it shifts the focus from possibly
      context-dependent aberrations to context-independent aberrations in functional
      network architecture. Rather than being analysed in isolation, the study of
      resting-state brain networks shows promise in linking results of task-based fMRI
      results, structural connectivity, molecular imaging findings, and performance
      measures of social cognition-which may prove crucial in furthering our
      understanding of the social brain.

PMID- 28766325
TI  - C-H Activation from Iron(II)-Nitroxido Complexes.
AB  - The reaction of nitroxyl radicals TEMPO (2,2',6,6'-tetramethylpiperidinyloxyl)
      and AZADO (2-azaadamantane-N-oxyl) with an iron(I) synthon affords iron(II)
      nitroxido complexes (Ar L)Fe(kappa1 -TEMPO) and (Ar L)Fe(kappa2 -N,O-AZADO) (Ar
      L=1,9-(2,4,6-Ph3 C6 H2 )2 -5-mesityldipyrromethene). Both high-spin iron(II)
      nitroxido species are stable in the absence of weak C-H bonds, but decay via N-O
      bond homolysis to ferrous or ferric iron hydroxides in the presence of 1,4
      cyclohexadiene. Whereas (Ar L)Fe(kappa1 -TEMPO) reacts to give a diferrous
      hydroxide [(Ar L)Fe]2 (MU-OH)2 , the reaction of four-coordinate (Ar L)Fe(kappa2 
      N,O-AZADO) with hydrogen atom donors yields ferric hydroxide (Ar L)Fe(OH)(AZAD).
      Mechanistic experiments reveal saturation behavior in C-H substrate and are
      consistent with rate-determining hydrogen atom transfer.

PMID- 28766327
TI  - Pathways of gram negative sepsis evaluation in a Nephrology Unit

PMID- 28766326
TI  - A review of Brucellosis in Iran: Epidemiology, Risk Factors, Diagnosis, Control,
      and Prevention
AB  - Brucellosis caused by species of Brucella is among the most prevalent zoonoses
      with the annual incidence of half a million cases globally. Most parts of Iran
      are endemic for brucellosis, and the annual incidence of the human and animal
      brucellosis is still high. At present, there is no safe and protective human
      vaccine against brucellosis, and the only preventive strategy is animal
      vaccination, which harbors significant disadvantages. Considering the
      identification of many immunogenic proteins in Brucella, several studies have
      recently been performed to evaluate the vaccine potency of such antigens as a new
      subunit vaccine candidate. This review represents an overview of brucellosis in
      Iran, including epidemiology, transmission routs, diagnosis, and treatment.
      Moreover, it mainly highlights the history of brucellosis control and prevention
      in Iran, including eradication programs, vast livestock vaccination programs, and
      subunit vaccine studies. It also discusses major problems that the country
      encounters with disease control. In recent years, Persian scientists have focused
      on evaluating the efficacy of best Brucella immunogens in vivo to introduce a new
      subunit vaccine. The results of some studies could demonstrate the vaccine
      potential of some immunogens.

PMID- 28766328
TI  - Phosphate-Imposed Constraints on Schwertmannite Stability under Reducing
      Conditions.
AB  - Schwertmannite is a ferric oxyhydroxysulfate mineral, which is common in acid
      sulfate systems. Such systems contain varying concentrations of phosphate (PO43-)
      an essential nutrient whose availability may be coupled to schwertmannite
      formation and fate. This study examines the effect of phosphate on schwertmannite
      stability under reducing conditions. Phosphate was added at 0, 80, 400, and 800
      MUmoles g-1 (i.e., zero, low, medium, and high loading) to schwertmannite
      suspensions which were inoculated with wetland sediment and suspended in N2
      purged artificial groundwater. pH remained between 2.7 and 4.3 over the 41 day
      experiment duration. Fe(II) accumulated in solution due to dissimilatory Fe(III)
      reduction, which was most pronounced at intermediate PO43- loadings (i.e., in the
      low PO43- treatment). Partial transformation of schwertmannite to goethite
      occurred in the zero and low PO43- treatments, with negligible transformation in
      higher PO43- treatments. Overall, the results suggest that intermediate PO43-
      loadings provide conditions which facilitate optimal reductive dissolution of
      schwertmannite. At zero PO43- loading, reductive dissolution appears to be
      constrained by the rapid transformation of schwertmannite to goethite, which
      thereby decreases the bioavailability of solid-phase Fe(III). Conversely, at high
      loadings, PO43- appears to stabilize the schwertmannite surface against
      dissolution; probably via the formation of strong surface complexes.

PMID- 28766329
TI  - Atomic Mechanism of Interfacial-Controlled Quantum Efficiency and Charge
      Migration in InAs/GaSb Superlattice.
AB  - A series of systematic electron microscopy imaging evidence are illustrated to
      prove that a high-quality interface is vital for enhancing quantum efficiency
      from 23 to 50% effectively, because improved crystal quality of each layer can
      suppress the disordered atom arrangement and enhance the carrier lifetime via
      decreasing the overall residual strain. The distribution width of charge rises
      and then falls as bias increasing, revealing the existence of an optimum
      operating voltage, which could be attributed to the proper energy band bending.
      Our results provide new insights into the understanding of the association
      between macro-property and microstructure of the superlattice system.

PMID- 28766330
TI  - Anti-IL8/AuNPs-rGO/ITO as an Immunosensing Platform for Noninvasive
      Electrochemical Detection of Oral Cancer.
AB  - An efficient electrochemical transducer matrix for biosensing devices requires
      specific characteristics, such as fast electron transfer, stability, high surface
      area, biocompatibility, and presence of specific functional groups, to facilitate
      biomolecule attachment. We demonstrate the fabrication of an electrochemical
      immunosensor based on a highly stable gold nanoparticles-reduced graphene oxide
      (AuNPs-rGO) composite material as a transducer matrix for label-free and
      noninvasive detection of salivary oral cancer biomarker interleukin-8 (IL8). The
      synergy between rGO and AuNPs allowed the immunosensor to exhibit fast response
      and high sensitivity due to the improved electron transfer behavior of the
      composite. The immunosensor shows very fast detection (9 min) of IL8 and high
      sensitivity with an experimental linear dynamic range of 500 fg mL-1 to 4 ng mL-1
      and a detection limit of 72.73 +/- 0.18 pg mL-1. The fabricated immunosensor
      exhibits excellent specificity toward the detection of IL8 in human saliva
      samples. Furthermore, the reusability and stability up to 3 months of the
      immunosensor demonstrates the commercial potential of this nanoplatform for the
      detection of other biomarkers of clinical relevance.

PMID- 28766331
TI  - Emissions from Electronic Cigarettes: Assessing Vapers' Intake of Toxic
      Compounds, Secondhand Exposures, and the Associated Health Impacts.
AB  - E-cigarettes likely represent a lower risk to health than traditional combustion
      cigarettes, but they are not innocuous. Recently reported emission rates of
      potentially harmful compounds were used to assess intake and predict health
      impacts for vapers and bystanders exposed passively. Vapers' toxicant intake was
      calculated for scenarios in which different e-liquids were used with various
      vaporizers, battery power settings and vaping regimes. For a high rate of 250
      puff day-1 using a typical vaping regime and popular tank devices with battery
      voltages from 3.8 to 4.8 V, users were predicted to inhale formaldehyde (up to 49
      mg day-1), acrolein (up to 10 mg day-1) and diacetyl (up to 0.5 mg day-1), at
      levels that exceeded U.S. occupational limits. Formaldehyde intake from 100 daily
      puffs was higher than the amount inhaled by a smoker consuming 10 conventional
      cigarettes per day. Secondhand exposures were predicted for two typical indoor
      scenarios: a home and a bar. Contributions from vaping to air pollutant
      concentrations in the home did not exceed the California OEHHA 8-h reference
      exposure levels (RELs), except when a high emitting device was used at 4.8 V. In
      that extreme scenario, the contributions from vaping amounted to as much as 12
      MUg m-3 formaldehyde and 2.6 MUg m-3 acrolein. Pollutant concentrations in bars
      were modeled using indoor volumes, air exchange rates and the number of hourly
      users reported in the literature for U.S. bars in which smoking was allowed.
      Predicted contributions to indoor air levels were higher than those in the
      residential scenario. Formaldehyde (on average 135 MUg m-3) and acrolein (28 MUg
      m-3) exceeded the acute 1-h exposure REL for the highest emitting
      vaporizer/voltage combination. Predictions for these compounds also exceeded the
      8-h REL in several bars when less intense vaping conditions were considered.
      Benzene concentrations in a few bars approached the 8-h REL, and diacetyl levels
      were close to the lower limit for occupational exposures. The integrated health
      damage from passive vaping was derived by computing disability-adjusted life
      years (DALYs) lost due to exposure to secondhand vapor. Acrolein was the dominant
      contributor to the aggregate harm. DALYs for the various device/voltage
      combinations were lower than-or comparable to-those estimated for exposures to
      secondhand and thirdhand tobacco smoke.

PMID- 28766332
TI  - Role of Quantum-Confinement in Anatase Nanosheets.
AB  - Despite most of the applications of anatase nanostructures rely on photoexcited
      charge processes, yet profound theoretical understanding of fundamental related
      properties is lacking. Here, by means of ab initio ground and excited-state
      calculations, we reveal, in an unambiguous way, the role of quantum confinement
      effect and of the surface orientation, on the electronic and optical properties
      of anatase nanosheets (NSs). The presence of bound excitons extremely localized
      along the (001) direction, whose existence has been recently proven also in
      anatase bulk, explains the different optical behavior found for the two
      orientations - (001) and (101) - when the NS thickness increases. We suggest also
      that the almost two-dimensional nature of these excitons can be related to the
      improved photoconversion efficiency observed when a high percentage of (001)
      facet is present in anatase nanocrystals.

PMID- 28766334
TI  - Facilitating Proton Transport in Nafion-Based Membranes at Low Humidity by
      Incorporating Multifunctional Graphene Oxide Nanosheets.
AB  - Nafion, as a state-of-the-art solid electrolyte for proton exchange membrane fuel
      cells (PEMFCs), suffers from drastic decline in proton conductivity with
      decreasing humidity, which significantly restricts the efficient and stable
      operation of the fuel cell system. In this study, the proton conductivity of
      Nafion at low relative humidity (RH) was remarkably enhanced by incorporating
      multifunctional graphene oxide (GO) nanosheets as multifunctional fillers.
      Through surface-initiated atom transfer radical polymerization of sulfopropyl
      methacrylate (SPM) and poly(ethylene glycol) methyl ether methacrylate, the
      copolymer-grafted GO was synthesized and incorporated into the Nafion matrix,
      generating efficient paths at the Nafion-GO interface for proton conduction. The
      Lewis basic oxygen atoms of ethylene oxide (EO) units and sulfonated acid groups
      of SPM monomers served as additional proton binding and release sites to
      facilitate the proton hopping through the membrane. Meanwhile, the hygroscopic EO
      units enhanced the water retention property of the composite membrane, conferring
      a dramatic increase in proton conductivity under low humidity. With 1 wt % filler
      loading, the composite membrane displayed the highest proton conductivity of 2.98
      * 10-2 S cm-1 at 80  degrees C and 40% RH, which was 10 times higher than that of
      recast Nafion. Meanwhile, the Nafion composite exhibited a 135.5% increase in
      peak power density at 60  degrees C and 50% RH, indicating its great application
      potential in PEMFCs.

PMID- 28766333
TI  - Monitoring Hydrogen Exchange During Protein Folding by Fast Pressure Jump NMR
      Spectroscopy.
AB  - A method is introduced that permits direct observation of the rates at which
      backbone amide hydrogens become protected from solvent exchange after rapidly
      dropping the hydrostatic pressure inside the NMR sample cell from denaturing (2.5
      kbar) to native (1 bar) conditions. The method is demonstrated for a pressure
      sensitized ubiquitin variant that contains two Val to Ala mutations. Increased
      protection against hydrogen exchange with solvent is monitored as a function of
      time during the folding process. Results for 53 backbone amides show narrow
      clustering with protection occurring with a time constant of ca. 85 ms, but
      slower protection is observed around a reverse turn near the C-terminus of the
      protein. Remarkably, the native NMR spectrum returns with this slower time
      constant of ca. 150 ms, indicating that the almost fully folded protein retains
      molten globule characteristics with severe NMR line broadening until the final
      hydrogen bonds are formed. Prior to crossing the transition state barrier,
      hydrogen exchange protection factors are close to unity, but with slightly
      elevated values in the beta1-beta2 hairpin, previously shown to be already lowly
      populated in the urea-denatured state.

PMID- 28766335
TI  - Functional Complementation Studies Reveal Different Interaction Partners of
      Escherichia coli IscS and Human NFS1.
AB  - The trafficking and delivery of sulfur to cofactors and nucleosides is a highly
      regulated and conserved process among all organisms. All sulfur transfer pathways
      generally have an l-cysteine desulfurase as an initial sulfur-mobilizing enzyme
      in common, which serves as a sulfur donor for the biosynthesis of sulfur
      containing biomolecules like iron-sulfur (Fe-S) clusters, thiamine, biotin,
      lipoic acid, the molybdenum cofactor (Moco), and thiolated nucleosides in tRNA.
      The human l-cysteine desulfurase NFS1 and the Escherichia coli homologue IscS
      share a level of amino acid sequence identity of ~60%. While E. coli IscS has a
      versatile role in the cell and was shown to have numerous interaction partners,
      NFS1 is mainly localized in mitochondria with a crucial role in the biosynthesis
      of Fe-S clusters. Additionally, NFS1 is also located in smaller amounts in the
      cytosol with a role in Moco biosynthesis and mcm5s2U34 thio modifications of
      nucleosides in tRNA. NFS1 and IscS were conclusively shown to have different
      interaction partners in their respective organisms. Here, we used functional
      complementation studies of an E. coli iscS deletion strain with human NFS1 to
      dissect their conserved roles in the transfer of sulfur to a specific target
      protein. Our results show that human NFS1 and E. coli IscS share conserved
      binding sites for proteins involved in Fe-S cluster assembly like IscU, but not
      with proteins for tRNA thio modifications or Moco biosynthesis. In addition, we
      show that human NFS1 was almost fully able to complement the role of IscS in Moco
      biosynthesis when its specific interaction partner protein MOCS3 from humans was
      also present.

PMID- 28766336
TI  - Kish Graphite Flakes as a Cathode Material for an Aluminum Chloride-Graphite
      Battery.
AB  - Nonaqueous, ionic liquid-based aluminum chloride-graphite batteries (AlCl3-GBs)
      are a highly promising post-Li-ion technology for low-cost and large-scale
      storage of electricity because these batteries feature exclusively highly
      abundant chemical elements and simple fabrication methods. In this work, we
      demonstrate that synthetic kish graphite, which is a byproduct of steelmaking,
      can be used as a cathode in AlCl3-GB and exhibits high capacities of <=142 mAh g
      1. The comprehensive characterization of kish graphite flakes and other forms of
      graphite by X-ray diffraction, Raman spectroscopy, and Brunauer-Emmett-Teller
      surface area analysis provides solid evidence that the exceptional
      electrochemical behavior of kish graphite flakes is mainly determined by the high
      structural order of carbon atoms, a low level of defects, and a unique "crater
      morphology". In view of the nonrocking chair operation mechanism of AlCl3-GB, we
      have tested the achievable energy densities as a function of the composition of
      chloroaluminate ionic liquid (AlCl3 content) and have obtained energy densities
      of up to 65 Wh kg-1. In addition, the kish graphite flakes can rapidly charge and
      discharge, offering high power densities of up to 4363 W kg-1.

PMID- 28766337
TI  - Evaluating Cellular Drug Uptake with Fluorescent Sensor Proteins.
AB  - We are introducing a new approach to evaluate cellular uptake of drugs and drug
      candidates into living cells. The approach is based on converting the protein
      target of a given class of compounds into a fluorescent biosensor. By measuring
      the binding of different compounds to their cognate biosensor in live cells and
      comparing these values to those measured in vitro, their cellular uptake and
      concentrations can be ranked. We demonstrate that our strategy enables the
      evaluation of the cellular uptake into the cytosol of 2 classes of inhibitors
      using two different sensor designs; first, sensors comprising the self-labeling
      protein SNAP conjugated with a chemically modified inhibitor shown for inhibitors
      of the enzyme human carbonic anhydrase II; and a label-free sensor for inhibitors
      of protein-protein interactions demonstrated for the protein pair p53-HDM2.

PMID- 28766338
TI  - Near-Infrared-Light-Responsive Magnetic DNA Microgels for Photon- and Magneto
      Manipulated Cancer Therapy.
AB  - Functional DNA molecules have been introduced into polymer-based nanocarrier
      systems to incorporate chemotherapy drugs for cancer therapy. Here is the first
      report of dual-responsive microgels composed of a core of Au nanorods and a shell
      of magnetic ionic liquid and DNA moieties in the cross-linking network
      simultaneously, as effective drug delivery vectors. TEM images indicated a
      magnetic polymer shell has an analogous "doughnut" shape which loosely surround
      the AuNRs core. When irradiated with a near-infrared-light (near-IR) laser, Au
      nanorods are the motors which convert the light to heat, leading to the release
      of the encapsulated payloads with high controllability. DNA acts not only as a
      cross-linker agent, but also as a gatekeeper to regulate the release of drugs.
      The internalization study and MTT assay confirm that these core-shell DNA
      microgels are excellent candidates which can enhance the cytotoxicity of cancer
      cells controlled by near-IR laser and shield the high toxicity of
      chemotherapeutic agents to improve the killing efficacy of chemotherapeutic
      agents efficiently in due course.

PMID- 28766339
TI  - Trajectory Surface-Hopping Dynamics Including Intersystem Crossing in
      [Ru(bpy)3]2.
AB  - Surface-hopping dynamics coupled to linear response TDDFT and explicit
      nonadiabatic and spin-orbit couplings have been used to model the ultrafast
      intersystem crossing (ISC) dynamics in [Ru(bpy)3]2+. Simulations using an
      ensemble of trajectories starting from the singlet metal-to-ligand charge
      transfer (1MLCT) band show that the manifold of 3MLCT triplet states is first
      populated from high-lying singlet states within 26 +/- 3 fs. ISC competes with an
      intricate internal conversion relaxation process within the singlet manifold to
      the lowest singlet state. Normal-mode analysis and principal component analysis,
      combined with further dynamical simulations where the nuclei are frozen,
      unequivocally demonstrate that it is not only the high density of states and the
      large spin-orbit couplings of the system that promote ISC. Instead, geometrical
      relaxation involving the nitrogen atoms is required to allow for state mixing and
      efficient triplet population transfer.

PMID- 28766340
TI  - Chemical Reactivity Descriptor for the Oxide-Electrolyte Interface in Li-Ion
      Batteries.
AB  - Understanding electrochemical and chemical reactions at the electrode-electrolyte
      interface is of fundamental importance for the safety and cycle life of Li-ion
      batteries. Positive electrode materials such as layered transition metal oxides
      exhibit different degrees of chemical reactivity with commonly used carbonate
      based electrolytes. Here we employed density functional theory methods to compare
      the energetics of four different chemical reactions between ethylene carbonate
      (EC) and layered (LixMO2) and rocksalt (MO) oxide surfaces. EC dissociation on
      layered oxides was found energetically more favorable than nucleophilic attack,
      electrophilic attack, and EC dissociation with oxygen extraction from the oxide
      surface. In addition, EC dissociation became energetically more favorable on the
      oxide surfaces with transition metal ions from left to right on the periodic
      table or by increasing transition metal valence in the oxides, where higher
      degree of EC dissociation was found as the Fermi level was lowered into the oxide
      O 2p band.

PMID- 28766341
TI  - Nonreciprocal Giant Magneto-Optic Effects in Transition-Metal Dichalcogenides
      without Magnetic Field.
AB  - Magnetic exchange field has been demonstrated to be effective in enhancing the
      valley splitting of monolayer transition-metal dichalcogenides experimentally.
      However, how magnetic exchange coupling affects the magnetooptical behaviors in
      massive Dirac systems remains elusive. Using k?.p? model and Kubo formula, we
      theoretically report that optical Hall conductivity and giant magnetooptical
      effects can be induced in monolayer transition-metal dichalcogenides even if
      there is no any magnetic field involved when considering magnetic exchange
      interaction. Such an unusual result originates from the fact that the existence
      of magnetic exchange coupling effectively enables the breaking of time reversal
      symmetry, which grants the removal of valley degeneracy and unveils the
      possibility of generation and manipulation of magnetooptical effects in monolayer
      transition-metal dichalcogenides with no need for magnetic field. Our results
      suggest that the presence of magnetic exchange coupling of transition-metal
      dichalcogenides represents an alternative strategy capable of inducing
      magnetoopitcal effects, which can be extended to other monolayer massive Dirac
      systems.

PMID- 28766342
TI  - Correction to "Modular, Step-Efficient Palladium-Catalyzed Cross-Coupling
      Strategy To Access C6-Heteroaryl 2-Aminopurine Ribonucleosides".

PMID- 28766343
TI  - Isothermal Point Mutation Detection: Toward a First-Pass Screening Strategy for
      Multidrug-Resistant Tuberculosis.
AB  - Point mutations in DNA are useful biomarkers that can provide critical
      classification of disease for accurate diagnosis and to inform clinical
      decisions. Conventional approaches to detect point mutations are usually based on
      technologies such as real-time polymerase chain reaction (PCR) or DNA sequencing,
      which are typically slow and require expensive lab-based equipment. While rapid
      isothermal strategies such as recombinase polymerase amplification (RPA) have
      been proposed, they tend to suffer from poor specificity in discriminating point
      mutations. Herein, we describe a novel strategy that enabled exquisite point
      mutation discrimination with isothermal DNA amplification, using mismatched
      primers in conjunction with a two-round enrichment process. As a proof of
      concept, the method was applied to the rapid and specific identification of drug
      resistant Mycobacterium tuberculosis using RPA under specific conditions. The
      assay requires just picogram levels of genomic DNA input, is sensitive and
      specific enough to detect 10% point mutation loading, and can discriminate
      between closely related mutant variants within 30 min. The assay was subsequently
      adapted onto a low-cost 3D-printed isothermal device with real-time analysis
      capabilities to demonstrate a potential point-of-care application. Finally, the
      generic applicability of the strategy was shown by detecting three other
      clinically important cancer-associated point mutations. We believe that our assay
      shows potential in a broad range of healthcare screening processes for detecting
      and categorizing disease phenotypes at the point of care, thus reducing
      unnecessary therapy and cost in these contexts.

PMID- 28766345
TI  - Prebiotics, intestinal microorganisms and atherosclerosis In Memory Emil Ginter,
      DSc, 1931-2017.

PMID- 28766344
TI  - Cell-Shaping Micropatterns for Quantitative Super-Resolution Microscopy Imaging
      of Membrane Mechanosensing Proteins.
AB  - Patterning cells on microcontact-printed substrates is a powerful approach to
      control cell morphology and introduce specific mechanical cues on a cell's
      molecular organization. Although global changes in cellular architectures caused
      by micropatterns can easily be probed with diffraction-limited optical
      microscopy, studying molecular reorganizations at the nanoscale demands
      micropatterned substrates that accommodate the optical requirements of single
      molecule microscopy techniques. Here, we developed a simple micropatterning
      strategy that provides control of cellular architectures and is optimized for
      nanometer accuracy single molecule tracking and three-dimensional super
      resolution imaging of plasma and nuclear membrane proteins in cells. This
      approach, based on fibronectin microcontact printing on hydrophobic organosilane
      monolayers, allows evanescent wave and light-sheet microscopy of cells whilst
      fulfilling the stringent optical demands of point reconstruction optical
      microscopy. By imposing steady-state mechanical cues on cells grown in these
      micropatterns, we reveal nanoscale remodeling in the dynamics and the structural
      organizations of the nuclear envelope mechanotransducing protein emerin and of
      the plasma membrane mechanosensing protein caveolin-1 using single particle
      tracking photoactivated localization microscopy and direct stochastic optical
      reconstruction microscopy imaging. In addition to allowing quantitative
      biophysical studies of mechanoresponsive membrane proteins, this approach
      provides an easy means to probe mechanical regulations in cellular membranes with
      high optical resolution and nanometer precision.

PMID- 28766346
TI  - Dose-dependent effects of adiponectin on ADAMTS-9 gene expression in human
      chondrocytes.
AB  - OBJECTIVE: A disintegrin and metalloproteinase with thrombospondin motifs
      (ADAMTS), comprising of 19 members is a family of peptidases. They have several
      vital functions in physiological and pathological processes in organisms. ADAMTS
      9 has aggrecanolytic activity and is responsible for degradation of aggrecan
      mainly in articular cartilage. It is known that adiponectin is the most
      abundantly secreted adipokine (adipocytokines), and the characteristics of
      adiponectin have not been elucidated yet. It was assumed that adiponectin has
      anti-inflammatory effect before. However, an inflammatory feature of adiponectin
      was shown in researches. In our study, the effect of adiponectin on ADAMTS-9 gene
      expression in primary human chondrocytes was investigated. METHODS: Primary human
      chondrocytes were exposed to adiponectin at 1, 4, 8 and 12 ug/ml doses for
      certain time period. Total RNA was isolated and reverse-transcribed by random
      primer after incubation. ADAMTS-9 and beta-actin genes expression levels were
      determined using real-time polymerase chain reaction (qRT-PCR). RESULTS: The
      highest upregulation of ADAMTS-9 gene expression level was found at 12 ug/ml dose
      of adiponectin and 48 h incubation. CONCLUSION: Adiponectin is the key element in
      the maintenance of cartilage homeostasis. Similarly, the involvement of
      adiponectin in articular inflammatory diseases was demonstrated in detail. These
      findings bring adiponectin into central place in the research to develop
      adiponectin based new therapy methods for arthritic diseases. Together with these
      findings, our results suggest that adiponectin may be involved in the degradation
      of articular cartilage by increasing ADAMTS-9 gene expression (Tab. 1, Fig. 3,
      Ref. 35).

PMID- 28766347
TI  - Effects of ceranib-2 on cell survival and TNF-alpha in colon cancer cell line.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of a novel anti
      cancer drug, ceranib-2, which targets the acid ceramidase, in human colon cancer
      cell line. MATERIALS AND METHODS: The cell lines were treated with 50 uM of
      ceranib-2. Relative mRNA expression of TNF-alpha, TNF-R1 and ASAH were assessed
      by quantitative RT-PCR. RESULTS: Ceranib-2 reduced cell viability in a dose
      dependent manner and the apoptotic values of cells following treatment with the
      dose of 50 uM were reduced significantly both at 24 h and 48 h compared to the
      control cells (p < 0.001). TNF-alpha receptor 1 (TNF-R1) mRNA levels were reduced
      significantly in the cell lines treated with both 25 uM and 50 uM of ceranib-2
      for 24 h compared to the control cells (p < 0.05), whereas the difference between
      the treatment and the control cell lines diminished at 48 h. The human acid
      ceramidase gene (ASAH) mRNA levels were significantly higher in the cell lines
      treated with 50 uM of ceranib-2 for 48 h than in the other cell lines (p <
      0.001). CONCLUSION: The study shows that ceranib-2 increased apoptosis by
      inducing ASAH expression and reduced TNF-R1 expression in human colon cancer cell
      lines in a dose and time-dependent manner (Fig. 3, Ref. 17).

PMID- 28766348
TI  - Roles of adiponectin and leptin as diagnostic markers in pancreatic cancer.
AB  - NTRODUCTION: Obesity is one of the most serious public health problem worldwide.
      Adipose tissue synthetize and secrete many growth factors and several cytokines
      known as adipokines. Studies demonstrated changes in the levels of these
      adipokines in many types of cancer associated with obesity. In this study, we
      aimed to evaluate the possible relationship between adiponectin and leptin levels
      with pancreas cancer and disease stage, representative of Turkish population.
      MATERIALS AND METHODS: The study was conducted between April 2012 - November
      2013. Study included 46 patients - 46 control subjects, who had pancreatic
      carcinoma. Results between the patients and the control group and relationship
      between the disease stage and results were evaluated. RESULTS: The comparison of
      preoperative adiponectin and leptin levels of the study group with the levels of
      the control group showed that there was no correlation with adiponectin and
      pancreas cancer. In contrast, leptin levels in the study group were significantly
      lower than in the control group. There was no correlation between the disease
      stage and adiponectin and leptin levels. CONCLUSION: There was a significant
      correlation between low leptin levels and pancreatic cancer, while adiponectin
      had no correlation. Differential diagnosis of pancreas cancer can be made by
      evaluating low leptin levels with elevated tumor markers (Tab. 3, Ref. 17).

PMID- 28766349
TI  - Effects of granulocyte colony-stimulating factor administration time on pain.
AB  - OBJECTIVE: This study was aimed at evaluating the effect of administration time
      of granulocyte colony-stimulating factor (G-CSF) on the level of pain related to
      G-CSF. METHODS: This study was carried out with 48 cancer patients divided into A
      and B groups. In the first stage of the study, the groups A and B were planned to
      be administered with G-CSF at 10: 00 and 14: 00, respectively. In the second
      stage, patients in groups A and B were asked to self-administer filgrastim at 14:
      00 and 10: 00, respectively. Patients were also asked to assess their pain level
      after G-CSF administration for a total of 4 times. RESULTS: According to the
      findings, the incidence of pain related to G-CSF was 91.7 %. The pain score after
      G-CSF being administered at 10: 00 was significantly higher compared to
      administration at 14: 00 in both groups (group A after 4, 8, and 12 hours: p <
      0.05; group B after 4 and 8 hours: p < 0.05). CONCLUSIONS: The results of the
      present study have demonstrated that the pain score related to G-CSF
      administration at 14:00 p.m. was significantly reduced. Thus, in order to
      minimize the pain, it will be more beneficial to administer G-CSF at 14: 00 (Tab.
      4, Ref. 31). Text in PDF www.elis.sk.

PMID- 28766350
TI  - The impact of using different doses of progesterone on memory performance.
AB  - OBJECTIVE: Progesterone is a sex hormone and its receptors are expressed
      throughout the hippocampus. This study was aimed at evaluating the effects of
      different doses of progesterone on memory. METHODS: Male rats were arbitrarily
      assigned to nine groups, namely Group I: control, Group II: control-cannula,
      Group III received 0.5 MUl of saline by cannula, Groups IV , V, VI, VII and VIII
      received progesterone in doses of 0.5, 1, 1.5, 2, and 3 MUg/ 0.5 MUl by cannula,
      respectively. Group IX received 0.5 MUl almond oil by cannula. Memory performance
      was tested in form of passive avoidance task. RESULTS: Our results indicated that
      progesterone at doses of 1.5 and 2 ug (p < 0.05) significantly increased the
      memory performance while at a dose of 3 ug (p < 0.05), it significantly decreased
      memory as compared to the control group. CONCLUSION: The current study revealed
      that the influence of progesterone on memory is related to its dose (Fig. 1, Ref.
      25).

PMID- 28766351
TI  - The impact of sleep deprivation on hippocampal-mediated learning and memory in
      rats.
AB  - BACKGROUND: To examine the impact of different types of sleep deprivation on
      hippocampal-mediated learning and memory in rats. METHODS: Forty-eight Sprague
      Dawley male rats were randomly assigned to 1 of 4 equal-size groups: (1) 12 hours
      of sleep per day (control). (2) total sleep deprivation (TSD), (3) rapid eye
      movement (REM) deprivation (RD), and (4) sleep restricted to 4 hours per day
      (SR). All rats were subjected to swimming training in the Morris water maze
      (MWM). At the end of the experiments, the rats were decapitated, and hippocampus
      tissue was analyzed for several neurotransmitters and receptors. RESULTS: The
      time spent at the target quadrant increased from 20.2 to 30.0 seconds in the
      control group on the third day of the experiment, whereas corresponding values
      increased from 20.2 to 21.8 seconds in the TSD group, 22.1 to 25.4 seconds in the
      RD group, and 21.2 to 32.0 sec in the SR group (p = 0.026). On the seventh day of
      the experiment, the values decreased to 25.0 seconds in controls, 22.5 in the RD
      group, and 23.6 in the SR group (p = 0.045). The TSD group demonstrated
      significant decreases in glutamate and serotonin levels compared with the control
      group. There was a significant increase in 5-HT2a receptor expression in all
      intervention groups compared with the controls. CONCLUSIONS: Our results of
      glutamate levels and 5-HT2a receptor expression in the hippocampus seem to be
      primarily involved in sleep and memory regulation (Tab. 2, Fig. 4, Ref. 59).

PMID- 28766352
TI  - Effect of different doses of pregabalin on skeletal muscle ischaemia-reperfusion
      injury in rats.
AB  - AIM/INTRODUCTION: Analgesic, anti-inflammatory and anti-apoptotic effects of
      pregabalin have been shown previously. In this study, we investigated the
      protective effect of different doses of pregabalin on skeletal muscle IR injury
      in rats. MATERIALS AND METHODS: 24 rats were randomly divided into 4 groups
      (Control, Ischaemia-Reperfusion (IR), IR-Pregabalin 50 mg, IR-Pregabalin 200 mg).
      Following IR, serum Ischemia Modified Albumin (IMA) and tissue Paraoxonase (PON)
      were studied and gastrocnemius muscle tissue was removed for histopathologic
      examination. RESULTS: Interstitial inflammation was higher in the IR group than
      in the control and Pregabalin 200 mg groups (p = 0.037, p = 0.037, respectively).
      Congestion was higher in the IR group than in the control, Pregabalin 50 and 200
      mg groups (p = 0.001, p = 0.004, p = 0.004, respectively). PON was lower in the
      IR group than in the Control, Pregabalin 50 and 200 mg groups (p = 0.001, p =
      0.007, p = 0.015, respectively). IMA was higher in the IR group than in the
      Control, Pregabalin 50 and 200 mg groups (p < 0.0001, all). CONCLUSION: We think
      that administration of pregabalin, more prominent at 200 mg, can reverse the
      injury that occurs in the skeletal muscle of IR-induced rats. Pregabalin can be
      safely used for analgesia in cases of IR (Tab. 2, Fig. 9, Ref. 41).

PMID- 28766353
TI  - The significance of Akt/NF-kappab signaling pathway in the posterior cataract
      animal model.
AB  - OBJECTIVE: To establish SD rat posterior capsular opacification (posterior
      capsular opacification- PCO) animal model, and to detect the expression of Akt/NF
      kb signaling pathway in the PCO model. METHODS: 30 healthy SD rats were randomly
      divided into control group (0d) and the experimental groups (7d and 14 d), there
      were 10 rats at all time points. All rats (right eye) were treated with the lens
      capsule, and the inflammatory reaction of the anterior segment of the eye and the
      occurrence of PCO at different time points were observed under the microscope.
      The TGF-beta concentration of humor aquosus was measured at the different time
      points by ELISA method. Eyeballs were removed after the rats were killed. RT-PCR
      method was used to detect the gene expression levels of Akt and NF-kappab and
      Westen Blot method to detect the protein expression of Akt, p-Akt, NF-kappab and
      p-NF-kappab. RESULTS: TGF-beta concentration, Akt and NF-kappab gene expression,
      and Akt, p-Akt, NF-kappab and p-NF-kappab protein expression in humor aquosus,
      increased with the time and the time-dependence was significant. CONCLUSION:
      Akt/NF-kappab signaling pathway may be closely related to the occurrence and
      development of PCO, which may be related to the role of protein phosphorylation
      (Fig. 5, Ref. 20).

PMID- 28766354
TI  - Risk perception of NSAIDs in hospitalized patients in Greece.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used
      analgesics worldwide in different syndromes. There is a relevant evidence about
      NSAIDs various adverse effects (AEs) on gastrointestinal, cardiovascular, renal,
      pulmonary, nervous systems. Many of these problems are preventable with respects
      to appropriate patient's risk perception. OBJECTIVES: The main goal of our study
      was to examine drug risk perception with relation to participation factors as
      comorbidities in patients. METHODS: A structured questionnaire was delivered to
      124 patients hospitalized at Department of Internal Medicine in a selected
      General Hospital in Greece. Data were evaluated using a descriptive statistics.
      RESULTS: Low awareness of NSAID risk was recorded, with 45.16 % of respondents
      unaware of any particular AEs. Lack of this knowledge appears to be attributed to
      low communication of physicians and pharmacists with patients about possible risk
      from comorbidity, over half of respondents (55.8 %) had history of hypertension,
      and 25.9 % were diabetics, which would increase the risk of NSAID therapy.
      CONCLUSION: Our study revealed a restricted knowledge about risk of NSAIDs in the
      studied population and showed some important data related to the presence of
      comorbidity in patients, which could potentiate the risk of cardiovascular AEs
      (Fig. 5, Ref. 22).

PMID- 28766355
TI  - Human race as indicator of 3D planning of soft tissue of face and
      multidisciplinary approach.
AB  - OBJECTIVE: The aim of this study was to determine the optimal parameters for 3D
      soft tissue planning for ortognatic treatment by gender and increases the
      effectiveness of multidisciplinary cooperation. METHODS: Craniofacial parameters
      which were analysed: nose breadth (al-al), bi-entocanthion breadth (en-en), bi
      zygomatic breadth (zy-zy), bi-gonial breadth (go-go), total facial height (n-gn),
      mouth breadth (ch-ch), morphologic face height (sn-gn), upper-lip height (Ls
      Stm), lower-lip height (Stm-Li) and pupils - mid-face (right). The statistically
      significant level was determined at p values < 0.05. RESULTS: We have determined
      the optimal parameters of chosen proportions for men and women as the common goal
      for ortodontist and maxilofacial surgeon. The gender and age influenced the
      variability of following parameters: bi-gonial breadth, total facial height and
      morphologic face height. CONCLUSION: The soft tissue values for craniofacial
      parameters can be used to identify the surgical-orthodontic goal for patient -
      europoid race. Due to the immigration and the mix of races it is necessary to
      take this fact into account (Tab. 3, Fig. 1, Ref. 41).

PMID- 28766356
TI  - Safety of platelet-rich plasma application in abdominal operations.

PMID- 28766357
TI  - Hemobilia due to a cystic artery pseudoaneurysm on ultrasound.
AB  - The present paper describes a case of hemobilia in a woman with a cystic artery
      pseudoaneurysm. The pseudoaneurysm could be seen with ultrasound, Doppler
      sonography and CT angiography. In our case, Doppler sonography was the most
      useful technique for diagnosis, revealing the turbulent forward and backwards
      flow within the gallbladder, representing the focally dilated artery. This was
      later confirmed by CT angiography. A recent bleeding site was found on the
      cholecystectomy specimen.

PMID- 28766358
TI  - Circulating Midregional Proadrenomedullin and Risk of Incident Abdominal Aortic
      Aneurysm: A Prospective Longitudinal Cohort Study.
AB  - Prospective clinical plasma biomarker studies in abdominal aortic aneurysm (AAA)
      pathogenesis have been hampered by the need for very large cohorts and long
      follow-up time. The main aim of the present study was to evaluate the association
      of adrenomedullin, a cardiovascular (CV) stress marker, and incident AAA risk.
      Prospective longitudinal cohort of middle-aged individuals from the CV cohort of
      the Malmo Diet and Cancer Study (n = 5551; 1991-1994) was assessed. Plasma
      concentrations of midregional proadrenomedullin (MR-proADM), C-reactive protein
      (CRP), and conventional risk factors were measured at baseline. Incidence of AAA
      was studied up to December 31, 2013. Cumulative incidence of AAA was 1.5% (men
      2.9%, women 0.5%). Mean age of individuals with incident AAA was 59.7 years at
      study entry, and AAA was diagnosed on average 14 years later. Adjusting for age,
      gender, smoking, body mass index, hypertension, diabetes mellitus, and CRP, MR
      proADM (hazard ratio: 1.28; 95% confidence interval: 1.01-1.62) was independently
      associated with incident AAA. The plasma biomarker MR-proADM seems to be a marker
      of AAA risk, implying that AAA development may be driven by long-standing CV
      stress on the aortic wall.

PMID- 28766359
TI  - Best practices in performing flow cytometry in a regulated environment: feedback
      from experience within the European Bioanalysis Forum.
AB  - Flow cytometry is a powerful tool that can be used for the support of
      (pre)clinical studies. Although various white papers are available that describe
      the set-up and validation of the instrumentation (the flow cytometer) and
      validation of flow cytometry methods, to date no guidelines exist that address
      the requirements for performing flow cytometry in a regulated environment. In
      this manuscript, the European Bioanalysis Forum presents additional practice
      guidance on the use of flow cytometry in the support of drug development programs
      and addresses areas that are not covered in the previous publications. The
      concepts presented here are based on the consensus of discussions in the European
      Bioanalysis Forum Topic Team 32, in meetings in Barcelona, Limelette and multiple
      telephone conferences.

PMID- 28766360
TI  - The Future of Quality Improvement in Breast Cancer: Patient-Reported Outcomes.

PMID- 28766361
TI  - Diagnostic specificity and sensitivity of PIVKAII, GP3, CSTB, SCCA1 and HGF for
      the diagnosis of hepatocellular carcinoma in patients with alcoholic liver
      cirrhosis.
AB  - Introduction Despite some new treatment possibilities, the improvement in
      survival rate for hepatocellular carcinoma (HCC) patients is still poor due to
      late diagnosis. The aim of this study was to investigate the diagnostic
      sensitivity and specificity of protein induced by vitamin K absence or antagonist
      II (PIVKAII), Glypican-3 (GP3), Cystatin B (CSTB), squamous cell carcinoma
      antigen 1 (SCCA1) and hepatocyte growth factor (HGF) as potential tumour markers
      for HCC in patients with alcoholic liver cirrhosis (ALC) using imaging techniques
      (MSCT and MRI) as reference standards. Patients and methods Eighty-three
      participants were included: 20 healthy volunteers, 31 patients with ALC and 32
      patients with HCC. Peripheral blood sampling was performed for each participant,
      and serum concentrations of PIVKAII, GP3, CSTB, SCCA1 and HGF were determined
      using commercial ELISA kits. Results Only serum concentrations of PIVKAII were
      significantly higher in HCC patients as compared with ALC and healthy controls
      (cut-off: 2.06  ug/L; AUC: 0.903), whereas individual diagnostic performance of
      other individual compounds was inadequate. The 'best' combination of tumour
      markers in our study includes all tested markers with AUC of 0.967. Conclusion
      While novel diagnostic tumour markers are urgently needed, the examined potential
      tumour markers, with the exception of PIVKAII seem to be inadequate for
      diagnosing HCC in ALC. Furthermore, probably the future is in finding the best
      optimal combination of tumour markers for diagnosing HCC based on cost
      effectiveness.

PMID- 28766362
TI  - A comparison study of bioanalytical methods for characterization of anti
      idursulfase antibodies.
AB  - AIM: Legacy methods with complex testing scheme for characterization of anti
      idursulfase antibodies (ADA) were simplified and optimized in order to meet
      current regulatory guidance and provide more timely and cost-effective support
      for routine patient care. RESULTS: To compare the performance of the original and
      updated methods, patient samples receiving commercially prescribed Elaprase
      treatment were analyzed by both test methods. The ADA and neutralizing antibody
      results obtained by both methods were highly correlated and the updated method
      had an overall higher ADA and neutralizing antibody positive rates and higher ADA
      titers. CONCLUSION: The updated methods and test schemes are much simpler, more
      sensitive, but are also highly comparable with the original methods for the
      measurement of total and neutralizing ADA.

PMID- 28766363
TI  - Future trends in outsourcing: a summary of the Bioanalysis Zone Survey.

PMID- 28766364
TI  - Overcoming disease-specific matrix effect in a clinical pharmacokinetic assay
      using a microfluidic immunoassay technology.
AB  - AIM: Etrolizumab, a humanized monoclonal antibody, has demonstrated clinical
      remission in a Phase II study of ulcerative colitis patients. In the Phase III
      program, a second indication, Crohn's disease was added. The pharmacokinetic
      ELISA used in the Phase I/II studies in normal human and ulcerative colitis sera
      exhibited matrix interference in the Crohn's disease population, necessitating
      implementation of a new technology. Methodology & results: Optimization of the
      original ELISA and assay redevelopment using different antibody pairs did not
      result in substantive improvements, necessitating implementation of an
      alternative technology for assay development. CONCLUSION: We highlight the
      challenges encountered with optimization/redevelopment of the original ELISA and
      discuss results of the new assay on the Gyros platform.

PMID- 28766365
TI  - Concomitant use of transvaginal sonography and Doppler indices improve diagnosis
      of adenomyosis.
AB  - This study was planned to investigate whether measuring of Doppler indices with
      TV-DUS improved the diagnosis of adenomyosis. Preoperative Doppler indices of
      subjects with a preliminary diagnosis of adenomyosis were compared with the
      histopathological results of excised specimens. Sensitivity, specificity and
      positive/negative predictive values (PPV, NPV) of the measured indices were also
      calculated. Sensitivity, specificity, PPV and NPV and positive and negative
      likelihood ratios (LR+) and (LR-) of TV-US in the diagnosis of adenomyosis were
      found to be 70.8%, 62.1%, 40.4%, 85.4%, 1.96 and 0.47, respectively. Sensitivity,
      specificity, PPV, NPV, LR + and LR - in the diagnosis of adenomyosis following
      the addition of TV-DUS were found to be 90%, 94.2%, 81.8%, 97%, 15.5 and 0.10,
      respectively. Concomitant use of TV-US and TV-DUS improved correct diagnosis of
      adenomyosis with high sensitivity.

PMID- 28766366
TI  - Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A)
      inhibitors: a survey of recent patent literature.
AB  - INTRODUCTION: Dual-specificity tyrosine phosphorylation-regulated kinase 1A
      (DYRK1A) is a eukaryotic serine-threonine protein kinase belonging to the CMGC
      group. DYRK1A hyperactivity appears to contribute to the development of a number
      of human malignancies and to cognitive deficits observed in Down syndrome and
      Alzheimer's disease. As a result, the DYRK1A kinase represents an attractive
      target for the synthesis and optimization of pharmacological inhibitors of
      potential therapeutic interest. Like most tyrosine kinase inhibitors developed up
      to the market, DYRK1A inhibitors are essentially acting by competing with ATP for
      binding at the catalytic site of the kinase. Areas covered: This paper reviews
      patent activity associated with the discovery of synthetic novel heterocyclic
      molecules inhibiting the catalytic activity of DYRK1A. Expert opinion: Despite
      the important role of DYRK1A in biological processes and the growing interest in
      the design of new therapeutic drugs, there are only few patented synthetic DYRK1A
      inhibitors and most of them were and are still developed by academic research
      groups, sometimes with industrial partners.

PMID- 28766367
TI  - Multi-tool accessibility assessment of government department websites:a case
      study with JKGAD.
AB  - PURPOSE: Nature of being accessible to all categories of users is one of the
      primary factors for enabling the wider reach of the resources published through
      World Wide Web. The accessibility of websites has been analyzed through W3C
      guidelines with the help of various tools. This paper presents a multi-tool
      accessibility assessment of government department websites belonging to the
      Indian state of Jammu and Kashmir. A comparative analysis of six accessibility
      tools is also presented with 14 different parameters. MATERIALS AND METHODS: The
      accessibility analysis tools used in this study for analysis are aChecker,
      Cynthia Says, Tenon, wave, Mauve, and Hera. These tools provide us the results of
      selected websites accessibility status on Web Content Accessibility Guidelines
      (WCAG) 1.0 and 2.0. RESULTS: It was found that there are variations in
      accessibility analysis results when using different accessibility metrics to
      measure the accessibility of websites. In addition to this, we have identified
      the guidelines which have frequently been violated. It was observed that there is
      a need for incorporating the accessibility component features among the selected
      websites. This paper presents a set of suggestions to improve the accessibility
      status of these sites so that the information and services provided by these
      sites shall reach a wider spectrum of audience without any barrier. Implications
      for rehabilitation The following points indicates that this case study of JKGAD
      websites comes under Rehabilitation focused on Visually Impaired users. Due to
      the universal nature of web, it should be accessible to all according to WCAG
      guidelines framed by World Wide Web Consortium. In this paper we have identified
      multiple accessibility barriers for persons with visual impairment while browsing
      the Jammu and Kashmir Government websites. Multi-tool analysis has been done to
      pin-point the potential barriers for persons with visually Impaired. Usability
      analysis has been performed to check whether these websites are suitable for
      persons with visual impairment. We provide some valuable suggestions which can be
      followed by developers and designers to minimize these potential accessibility
      barriers.Based on aforementioned key points, this article helps the persons with
      disability especially Visually Impaired Users to access the web resources better
      with the implementation of identified suggestions.

PMID- 28766368
TI  - Passing the Threshold of One Justice System to the Next: Challenges of Emerging
      Young Adults in Hong Kong's Adult Criminal Justice Process.
AB  - In many criminal justice systems, there is a clear separation for juvenile and
      adult defendants. However, those in between, referred to as emerging young adult
      defendants (ages 18-25 years), are treated as adult defendants despite a growing
      recognition that emerging adulthood is a distinct period in the life course. The
      aim of this present study is to investigate the experiences and challenges faced
      by emerging young adult defendants ( N = 25) in Hong Kong's adult criminal
      justice process. Through in-depth semistructured interviews, it was found that
      emerging young adult defendants demonstrated a lack of understanding regarding
      their rights and the legal procedures, faced stress in being caught up in the
      criminal justice process, and were susceptible to influence by others,
      particularly family members, in making legal decisions. Implications and future
      directions of study are discussed.

PMID- 28766369
TI  - The onset of uncertainty facilitates the learning of new associations by
      increasing attention to cues.
AB  - Past research in animals has suggested that attention is distributed to exploit
      known relationships between stimuli (e.g., Mackintosh, 1975) and explore stimuli
      whose consequences are uncertain (e.g., Pearce & Hall, 1980). The resulting
      changes in attention influence how animals learn new information involving those
      stimuli. While there is strong support for exploitative attention and its effects
      on learning in humans, the evidence for exploratory attention is less well
      developed. Two experiments examined whether preferential allocation of attention
      (as measured by eye-gaze) to cues associated with uncertainty leads to more rapid
      learning of new associations involving these cues in the future. In each
      experiment, participants first learned about compounds containing one predictive
      cue and one non-predictive cue. The level of uncertainty during this first stage
      of training was also manipulated: cue-outcome relationships were either
      deterministic (certain) or probabilistic (uncertain). In a second stage, new cue
      outcome relationships were trained and the uncertainty of these relationships
      could be resolved by learning about the previously non-predictive cues. As a
      result of the manipulation of uncertainty in the first stage, some participants
      experienced a sudden onset of uncertainty at the start of this second stage,
      while others experienced a stable level of uncertainty throughout the experiment.
      Experiment 1 showed that participants who experienced an onset of uncertainty
      learned novel cue-outcome associations faster than participants for whom
      uncertainty was constant. Furthermore, participants experiencing unexpected
      uncertainty showed a greater increase in attention to cues in Stage 2. When the
      first stage of training was extended in Experiment 2 a larger difference in the
      rate of learning between the two conditions was observed in the second stage. We
      argue that this represents evidence for an effect of exploratory attention on
      rate of learning in humans.

PMID- 28766370
TI  - Predictors for total hospital and cardiology cost claims among patients with
      atrial fibrillation initiating dabigatran or acenocoumarol in The Netherlands.
AB  - AIMS: The prevalence of atrial fibrillation (AF) has increased over the past
      years due to aging of the population, and healthcare costs associated with AF
      reflect a significant financial burden. The aim of this study was to explore
      predictors for the real-world AF-related in-hospital costs in patients that
      recently initiated anticoagulation with acenocoumarol or dabigatran. METHODS:
      Predictors for claimed total hospital care costs and cardiology costs in AF
      patients were explored by using hospital financial claims data from propensity
      score matched patient groups in a large Dutch community hospital. This study
      analyzed the total dataset (n = 766) and carried out a secondary analysis for all
      matched pairs of anticoagulation naive AF patients (n = 590) by ordinal
      regression. RESULTS: Dabigatran was a predictor for significantly lower
      cardiology and total hospital care costs (Odds Ratio [OR] = 0.43, 95% confidence
      interval (CI) = 0.33-0.57; and OR = 0.60, 95% CI = 0.46-0.79, respectively).
      Female gender was a predictor for lower total hospital care costs. Predictors for
      an increase in total hospital care costs were the occurrence of stroke or
      systemic embolism, major bleeding, and minor bleeding. The costs predictors were
      comparable when limiting the analysis to patients that were anticoagulation
      naive. Age and CHA2DS2-VASc were not predictors for either cardiology or total
      hospital care costs in both analyses. CONCLUSION: Dabigatran treatment was as a
      predictor for lower cardiology costs and lower total hospital care costs in AF
      patients that initiated oral anticoagulation.

PMID- 28766371
TI  - Reading comprehension and its relationship with working memory capacity when
      reading horizontally scrolling text.
AB  - The horizontally scrolling format, where text is presented in a single line
      drifting right to left, is relatively commonly used to display text on digital
      screens. This format presents a potentially challenging reading situation as the
      text must be followed smoothly to the left (to track individual words) while
      rightward eye movements are made as usual to progress through the text. This
      conflict may reduce attention allocated to upcoming text. Returning to previously
      encountered text is also more difficult with this format. Here, a sustained
      reading comprehension task was used to compare performance with horizontally
      scrolling and multi-line static text formats. Results showed that literal
      comprehension can be reasonably well maintained with scrolling text, although
      small decrements are seen at faster scrolling rates. However, they indicated that
      this format makes it more difficult to answer questions requiring an inference to
      be made. The contribution of working memory capacity and the impact of display
      speed on these effects were considered. These findings have implications for the
      application of this format in digital media and also more widely for the
      conditions required for successful in-depth reading comprehension with any text
      format.

PMID- 28766372
TI  - Role of event centrality and emotion regulation in posttraumatic stress disorder
      symptoms among internally displaced persons.
AB  - BACKGROUND: Event centrality and emotion regulation in relation to posttraumatic
      stress disorder (PTSD) have been documented in various global samples especially
      in Western cultures; but internally displaced persons (IDPs) still constitute an
      underrepresented population in psychotraumatology literature. This study tested
      the roles of event centrality and emotion regulation strategies (cognitive
      reappraisal and expressive suppression) in PTSD symptoms among IDPs in Nigeria.
      DESIGN: The multi-group cross-sectional design was adopted. METHODS: Tiv language
      versions of the Centrality of Events Scale, Emotion Regulation Questionnaire, and
      Harvard Trauma Questionnaire were completed by 859 IDPs in two camps located in
      Benue State, North-central region of Nigeria. RESULTS: Hierarchical multiple
      linear regression results indicated that event centrality positively predicted
      PTSD symptoms. Cognitive reappraisal was a negative predictor of PTSD symptoms
      while expressive suppression was a positive predictor of PTSD symptoms.
      Bonferroni corrections indicated that expressive suppression was the strongest
      predictor of total PTSD symptoms, avoidance/numbing symptoms, and hyper-arousal
      symptoms; but event centrality was the most robust predictor of PTSD intrusion/re
      experiencing symptoms. CONCLUSION: The findings underscore recent developments in
      psychotraumatology indicating that the extent to which individual differences
      impact the development of PTSD is essential in clinical psychology research and
      practice.

PMID- 28766373
TI  - Prediction of the outcome of children who had a language delay at age 2 when they
      are aged 4: Still a challenge.
AB  - PURPOSE: This study investigated the role that variables related to children and
      their environment play in the prediction of outcomes at 4 years of age for
      children with a language delay at 2 years. METHOD: A longitudinal study was
      undertaken where 64 children (45 boys, 19 girls; mean age = 53.3 months; SD =
      4.4) with language delay at age 2 years were re-evaluated at age 4 years. Three
      developmental trajectories were analysed. RESULT: The early stages of grammar, as
      estimated by mean length of utterance at 3.5 years, are an important prognosis
      factor of subsequent language impairment (LI). Children who are exposed to
      several risk factors simultaneously are more likely to have a language delay (LD)
      or a LI, but the profile of LD children is more akin to that of the typically
      developing (TD) children. Children with LI tend to have profiles with a greater
      number of risk factors. CONCLUSION: The results of this study encourage different
      intervention approaches depending on the child's language profile at 2 years, due
      to differing language prognosis. The results also point to the need to assess the
      child's environment. Future studies with large diverse population samples may
      give more precise information on potential risk factors and their cumulative
      effect.

PMID- 28766374
TI  - Biotechnological production and practical application of L-asparaginase enzyme.
AB  - L-asparaginase is a vital enzyme of medical importance, and renowned as a
      chemotherapeutic agent. The relevance of this enzyme is not only limited as an
      anti-cancer agent, it also possesses a wide range of medical application. The
      application includes the antimicrobial property, treatment of infectious
      diseases, autoimmune diseases, canine and feline cancer. Apart from the health
      care industry, its significance is also established in the food sector as a food
      processing agent to reduce the acrylamide concentration. L-asparaginase is known
      to be produced from various bacterial, fungal and plant sources. However, there
      is a huge market demand due to its wide range of application. Therefore, the
      industry is still in the search of better-producing source in terms of high yield
      and low immunogenicity. It can be produced by both submerged and solid state
      fermentation, and each fermentation process has its own merits and demerits. This
      review paper focuses on its improved production strategy by adopting statistical
      experimental optimization techniques, development of recombinant strains, through
      mutagenesis and nanoparticle immobilization, adopting advanced and cost-effective
      purification techniques. Available research literature proves the competence and
      therapeutic potential of this enzyme. Therefore, research orientation toward the
      exploration of this clinical significant enzyme has to be accelerated. The
      objectives of this review are to discuss the high yielding sources, current
      production strategies, improvement of production, effective downstream processing
      and therapeutic application of L-asparaginase.

PMID- 28766375
TI  - Powerlessness, Normalization, and Resistance: A Foucauldian Discourse Analysis of
      Women's Narratives On Obstetric Fistula in Eastern Sudan.
AB  - Eastern Sudan has high prevalence of female circumcision and child marriage
      constituting a risk for developing obstetric fistula. Few studies have examined
      gender roles' relation with obstetric fistula in Sudan. To explore the associated
      power-relations that may put women at increased risk for developing obstetric
      fistula, we conducted nine interviews with women living with obstetric fistula in
      Kassala in eastern Sudan. Using a Foucauldian discourse analysis, we identified
      three discourses: powerlessness, normalization, and covert resistance. Existing
      power-relations between the women and other societal members revealed their
      internalization of social norms as absolute truth, and influenced their status
      and decision-making power in regard to circumcision, early marriage, and other
      transformative decisions as well as women's general behaviors. The women showed
      subtle resistance to these norms and the harassment they encountered because of
      their fistula. These findings suggest that a more in-depth contextual assessment
      could benefit future maternal health interventions.

PMID- 28766376
TI  - The association of minimum wage change on child nutritional status in LMICs: A
      quasi-experimental multi-country study.
AB  - There is recognition that social protection policies such as raising the minimum
      wage can favourably impact health, but little evidence links minimum wage
      increases to child health outcomes. We used multi-year data (2003-2012) on
      national minimum wages linked to individual-level data from the Demographic and
      Health Surveys (DHS) from 23 low- and middle-income countries (LMICs) that had
      least two DHS surveys to establish pre- and post-observation periods. Over a pre-
      and post-interval ranging from 4 to 8 years, we examined minimum wage growth and
      four nutritional status outcomes among children under 5 years: stunting, wasting,
      underweight, and anthropometric failure. Using a differences-in-differences
      framework with country and time-fixed effects, a 10% increase in minimum wage
      growth over time was associated with a 0.5 percentage point decline in stunting (
      0.054, 95% CI (-0.084,-0.025)), and a 0.3 percentage point decline in failure (
      0.031, 95% CI (-0.057,-0.005)). We did not observe statistically significant
      associations between minimum wage growth and underweight or wasting. We found
      similar results for the poorest households working in non-agricultural and non
      professional jobs, where minimum wage growth may have the most leverage. Modest
      increases in minimum wage over a 4- to 8-year period might be effective in
      reducing child undernutrition in LMICs.

PMID- 28766378
TI  - Corrigendum.

PMID- 28766377
TI  - Stigma towards mental illness and substance use issues in primary health care:
      Challenges and opportunities for Latin America.
AB  - Stigma towards mental illness and addictive disorders is a global problem and one
      of the main obstacles in tackling this issue remains the effective integration of
      mental health services into primary health care (PHC). In Latin America,
      information has significantly increased on the existence of stigma; however,
      little is known about effective interventions to prevent stigma and promote
      recovery-oriented practices in PHC. The aim of this study is to understand the
      existing evidence regarding mental health stigma in PHC with a special focus on
      the Latin American region. A scoping review of the literature related to mental
      health stigma in PHC was conducted. Two hundred and seventeen articles were
      evaluated; 74 met inclusion criteria and 14 additional articles were selected
      from references of search results. Results were subdivided into five different
      perspectives: users, family members and significant others, health professionals,
      contextual factors, and potential effective interventions. Only nine studies were
      based in Latin America, and only one described an intervention to reduce stigma
      in mental health services, not specifically in PHC. We found an urgent need to
      develop interventions to understand and reduce stigma in PHC settings, especially
      in Latin America.

PMID- 28766380
TI  - Milk Vending Does Not Improve College Students' Milk and Calcium Intakes.
AB  - In the transition from adolescence to young adulthood, overall diet quality
      decreases, including a reduction in both dairy and calcium consumption. The
      objective of this pilot study was to determine the impact of milk vending on milk
      and calcium intakes in college students. Participants were 124 college students
      living in dorms at a large public university (Fall 2012). Milk vending machines
      were installed in two campus dorms. Before and 2 months after installation,
      students were surveyed about milk and calcium intakes, as well as attitudes
      regarding milk vending. Sales data for the newly installed machines were also
      collected between the pre- and posttest surveys. Students reported similar milk
      and calcium consumption before and after the intervention. Mean calcium intakes
      were lower than the recommended dietary allowance for students in either life
      stage group (18 years old or 19 years and older). Milk vending sales data showed
      that during the study period, approximately nine bottles of milk were bought each
      day from the two dorms combined. Results from this study suggest that milk
      vending alone may not be an effective strategy for preventing the commonly
      observed decrease in milk and calcium intakes among college students.

PMID- 28766379
TI  - Risk of gastrointestinal complications in breast cancer patients treated with
      neratinib: a meta-analysis.
AB  - BACKGROUNDS: Neratinib is a potent EGFR/HER2 kinase inhibitor. Gastrointestinal
      complications (i.e. diarrhea, vomiting and nausea) are the most common adverse
      events. In this study, we aimed to investigate (1) the overall incidence and
      relative risk (RR) of diarrhea, vomiting and nausea and (2) whether combination
      neratinib therapy increased the incidence of gastrointestinal complications
      versus neratinib alone. METHODS: Relevant studies were identified from the PubMed
      database, from abstracts presented at the American Society of Clinical Oncology
      annual conference and from the Web of Science database. Incidences, RRs, and 95%
      confidence intervals (CIs) were calculated. RESULTS: The incidences of all-grade
      diarrhea, vomiting and nausea in the neratinib groups were 89% (95% CI = 77-95%),
      31% (95% CI = 25-37%) and 44% (95% CI = 33-55%), respectively. The neratinib arms
      significantly increased the risk of diarrhea and vomiting in comparison with the
      control groups (diarrhea: all-grade, RR = 2.06, 95% CI = 1.38-3.08, P = 0.0004;
      grade 3/4, RR = 8.77, 95% CI = 2.91-26.40, P = 0.0001; vomiting: all-grade, RR =
      2.02, 95% CI = 1.10-3.71, P = 0.02; grade 3/4, RR = 7.10, 95% CI = 3.33-15.15, P
      < 0.00001). CONCLUSIONS: Our meta-analysis demonstrates that the neratinib arms
      are associated with a significantly increased risk of diarrhea and vomiting.

PMID- 28766381
TI  - Development and validation of an enzyme-linked immunosorbent assay to measure
      free eculizumab concentration in serum.
AB  - AIM: Eculizumab is a monoclonal antibody toward C5 fraction of the complement
      system. It is approved to treat paroxysmal nocturnal hemoglobinuria and atypical
      hemolytic uremic syndrome. To perform pharmacokinetic studies and therapeutic
      drug monitoring, a validated assay is required. MATERIALS & METHODS: An indirect
      ELISA with recombinant human C5 sensitized microtiter plates were developed.
      RESULTS: The assay allows the measurement of free eculizumab concentration in
      human serum. The LOD, LLOQ and ULOQ were 0.091, 0.25 and 82.35 mg/l,
      respectively. The assay meets EMA and US FDA guidelines criteria for the
      validation of a ligand-binding assay. CONCLUSION: This method is validated and
      can be used in PK and PK-PD studies as well as to perform therapeutic drug
      monitoring of free eculizumab.

PMID- 28766382
TI  - Heart rate control is associated with reduced cardiovascular events in Asian
      patients with coronary artery disease treated with bisoprolol (BISO-CAD): results
      from a multi-national, real-world experience.
AB  - OBJECTIVE: To evaluate the association between decrease in resting heart rate
      (RHR) and occurrence of composite cardiac clinical outcomes in coronary artery
      disease (CAD) patients after bisoprolol treatment. METHODS: This phase IV, multi
      national, single-arm, open-label, non-randomized, observational trial was
      conducted between October 2011 and July 2015 across 42 hospitals from China,
      South Korea and Vietnam. RESULTS: Analysis of 866 patients (mean age 63.85 +/-
      10.35; mean RHR at baseline 75.71 +/- 6.87 bpm in intent-to-treat [ITT]; 75.56 +/
      6.73 in efficacy analysis [EA] sets) was performed. Patients with lower mean RHR
      had fewer composite cardiac events and patients with RHR of 69-74 bpm reported
      significantly higher outcomes than patients with RHR <65 bpm (p = .0449). A
      significant association with occurrence of the composite cardiac outcome and
      hospital admission for unstable angina or revascularization was reported in the
      EA set (regression estimate: 0.03, 95% CI 0.00-0.07, p = .0412) and not in the
      ITT set for bisoprolol treated CAD patients. Composite cardiac outcomes
      significantly increased in patients with mean RHR >=70 bpm compared to patients
      with mean RHR <70 bpm (p = .0328). Adverse events (AEs) were reported in 206
      (23.8%) patients, of whom 102 (11.8%) patients had serious adverse event (SAEs).
      Among the patients with SAEs, 11 (1.3%) patients died. Treatment related adverse
      events were only 12 (1.4%). No treatment related SAE happened. CONCLUSION: The
      findings showed bisoprolol to be efficacious, in terms of lowering RHR and
      causing a significant decrease in the occurrence of the composite cardiac
      outcome, as well as safe in Asian patients with CAD.

PMID- 28766383
TI  - Are we ready for the evolution of electronic laboratory notebooks in regulated
      bioanalysis?

PMID- 28766384
TI  - "Did I make the right decision?": The difficult and unpredictable journey of
      being a surrogate decision maker for a person living with dementia.
AB  - Many people living with dementia eventually lose the capacity to make their own
      decisions and will rely on another person - a surrogate decision maker - to make
      decisions on their behalf. It is important - especially with the increasing
      prevalence of dementia - that the role of surrogate decision maker is understood
      and supported. This qualitative study explored the experiences of 34 surrogate
      decision makers of persons living with dementia in Australia. Face-to-face and
      telephone interviews were conducted over six months in 2014. Five themes were
      identified: becoming the only - or main - surrogate decision maker; growing into
      the role of surrogate decision maker; dealing with the stress of making
      decisions; having to challenge healthcare professionals; and getting support - or
      not - from family members. An overarching construct tying the themes together is
      the description of the participants' experience as being on a difficult and
      unpredictable journey. Healthcare professionals can provide support by acting as
      empathic guides on this journey.

PMID- 28766386
TI  - Palestinian women, conflict and human rights.

PMID- 28766385
TI  - Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and
      protective effects of various compounds in vivo and in vitro.
AB  - Paracetamol (APAP) is one of the most widely used and popular over-the-counter
      analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP
      overdose can cause severe liver injury, liver necrosis and kidney damage in human
      beings and animals. Many studies indicate that oxidative stress is involved in
      the various toxicities associated with APAP, and various antioxidants were
      evaluated to investigate their protective roles against APAP-induced liver and
      kidney toxicities. To date, almost no review has addressed the APAP toxicity in
      relation to oxidative stress. This review updates the research conducted over the
      past decades into the production of reactive oxygen species (ROS), reactive
      nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and
      ultimately their correlation with the toxicity and metabolism of APAP. The
      metabolism of APAP involves various CYP450 enzymes, through which oxidative
      stress might occur, and such metabolic factors are reviewed within. The
      therapeutics of a variety of compounds against APAP-induced organ damage based on
      their anti-oxidative effects is also discussed, in order to further understand
      the role of oxidative stress in APAP-induced toxicity. This review will throw new
      light on the critical roles of oxidative stress in APAP-induced toxicity, as well
      as on the contradictions and blind spots that still exist in the understanding of
      APAP toxicity, the cellular effects in terms of organ injury and cell signaling
      pathways, and finally strategies to help remedy such against oxidative damage.

PMID- 28766387
TI  - Adapting to change: interactions of Candida albicans with its environment.

PMID- 28766388
TI  - Surgical Training With Live Animal Models for Laparoscopic Gastrectomy.

PMID- 28766389
TI  - Pharmacokinetics, efficacy and safety of the rituximab biosimilar CT-P10.
AB  - INTRODUCTION: Rituximab, an anti-CD20 monoclonal antibody, is a key therapeutic
      in the treatment of B cell lymphomas and rheumatoid arthritis (RA). Global rates
      of non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL) and RA are
      increasing, with a concomitant rise in individual and overall treatment costs. As
      such, biosimilar development may help facilitate greater access to treatment. The
      rituximab biosimilar CT-P10 (Truxima(r)) has recently received approval in Europe
      and South Korea for all indications held by reference rituximab (RTX). Areas
      covered: Here, the unmet needs and current market in the treatment of NHL, CLL
      and RA are outlined, followed by a comprehensive examination of the analytical,
      pre-clinical and clinical data demonstrating the equivalence and similarity of CT
      P10 to RTX including with respect to pharmacokinetics, efficacy, safety and
      immunogenicity. Expert commentary: The rising treatment costs of NHL, CLL and RA
      pose a challenge to constrained healthcare budgets worldwide. Biosimilars may
      provide an effective solution to this conundrum. CT-P10 is equivalent to RTX in
      terms of efficacy and pharmacokinetics, and has a similar safety and
      immunogenicity profile. Approved in all indications held by RTX, CT-P10 has the
      potential to reduce treatment costs and thereby increase patient access to
      rituximab therapy.

PMID- 28766390
TI  - Burden of rheumatoid arthritis in the Nordic region, 1990-2015: a comparative
      analysis using the Global Burden of Disease Study 2015.
AB  - OBJECTIVE: To report mortality and disability due to rheumatoid arthritis (RA) in
      the Nordic region (Denmark, Finland, Greenland, Iceland, Norway, and Sweden)
      using data from the Global Burden of Disease Study (GBD) 2015. METHOD: Using the
      results of GBD 2015, we present rates and trends in prevalence, mortality, years
      of life lost, years lived with disability (YLD), and disability-adjusted life
      years (DALYs) of RA in the Nordic region during 1990-2015. RESULTS: In 2015, the
      age-standardized prevalence of RA was higher in the Nordic region than the global
      level (0.44%, 95% uncertainty interval 0.40-0.48%, vs 0.35%, 0.32-0.38%). For
      women (men), DALYs increased by 2.4% (12.9%), from 29 263 (10 909) in 1990 to 29
      966 (12 311) in 2015. The burden of RA as a proportion of total DALYs in women
      (men) increased from 0.90% (0.29%) in 1990 to 0.94% (0.36%) in 2015. Age
      standardized DALY rates declined in all countries except Denmark and Greenland
      between 1990 and 2015. Of 315 conditions studied, RA was ranked as the 16th
      (37th) leading cause of YLD in women (men) in the region. Of 195 countries
      studied, Greenland, Finland, Denmark, Norway, Sweden, and Iceland had the 7th,
      11th, 28th, 38th, 48th, and 78th highest age-standardized YLD rates for RA,
      respectively. CONCLUSIONS: The prevalence of RA in the Nordic region is higher
      than the global average. Current trends in population growth and ageing suggest a
      potential increase in RA burden in the coming decades in the region that should
      be considered in healthcare resources allocation.

PMID- 28766391
TI  - Stressful life events as a trigger for rheumatoid arthritis onset within a year:
      a case-control study.

PMID- 28766392
TI  - Vagal influences in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease with
      a prevalence of 0.5-1% in Western populations. Conventionally, it is treated with
      therapeutic interventions that include corticosteroids, disease-modifying anti
      rheumatic drugs, and biological agents. RA exerts a significant socio-economic
      burden and despite the use of existing treatments some patients end up with
      disabling symptoms. The autonomic nervous system (ANS) is a brain-body interface
      that serves to regulate homeostasis by integrating the external environment with
      the internal milieu. The main neural substrate of the parasympathetic branch of
      the ANS is the vagus nerve (VN). The discovery of the role of the ANS and the VN
      in mediating and dampening the inflammatory response has led to the proposal that
      modulation of neural circuits may serve as a valuable therapeutic tool. Recent
      studies have explored the role of the VN in this inflammatory reflex and have
      provided evidence that stimulation may represent a novel new therapeutic
      intervention. Accumulating evidence suggests that modulation of the
      parasympathetic tone results in a broad physiological multi-level response,
      including decreased pro-inflammatory cytokine response in terms of tumour
      necrosis factor-alpha, interleukin-1 (IL-1), and IL-6, and may result in an
      enhanced macrophage switch from M1 to M2 cells and potentially an increased level
      of the anti-inflammatory cytokine IL-10. Therefore, therapeutic electrical
      modulation of the VN may serve as an alternative, non-pharmacological,
      neuroimmunomodulatory intervention in RA in the future. This review gives a
      focused introduction to the mechanistic link between the ANS and the immune
      system.

PMID- 28766393
TI  - How to bring the news ... peak-end effects in children's affective responses to
      peer assessments of their social behavior.
AB  - The retrospective evaluation of an event tends to be based on how the experience
      felt during the most intense moment and the last moment. Two experiments tested
      whether this so-called peak-end effect influences how primary school students are
      affected by peer assessments. In both experiments, children (ages 7-12) assessed
      two classmates on their behaviour in school and then received two manipulated
      assessments. In Experiment 1 (N  = 30), one assessment consisted of four negative
      ratings and the other of four negative ratings with an extra moderately negative
      rating added to the end. In Experiment 2 (N  = 44), one assessment consisted of
      four positive ratings, and the other added an extra moderately positive rating to
      the end. Consistent with the peak-end effect, the extended assessment in
      Experiment 1 and the short assessment in Experiment 2 were remembered as more
      pleasant and less difficult to deal with, which shaped children's peer assessment
      preferences and prospective choices of which assessment to repeat. These findings
      indicate that the process of peer assessment can be improved by ending the
      feedback with the most positive part of the assessment.

PMID- 28766394
TI  - Moral distress in Iranian pediatric nurses.
AB  - BACKGROUND: Moral distress is a very common experience in the nursing profession,
      and it is one of the main reasons for job dissatisfaction, burnout, and quitting
      among nurses. For instance, morally difficult situations in taking care of child
      patients who are severely ill may lead to moral distress for nurses. However,
      most of the studies about moral distress have been conducted on nurses of special
      wards and adult medical centers with much focus on developed countries.
      Subsequently, little has been researched on this topic among nurses in other
      nations such as Iran, and most certainly, there has been hardly any such research
      involving Iranian pediatric nurses. Aim/objectives: This study was conducted to
      evaluate moral distress among nurses in selected pediatric hospitals in Tehran,
      Iran. RESEARCH DESIGN: This cross-sectional study was conducted on eligible
      nurses who were selected through proportional stratified sampling and who
      completed demographic characteristics and the pediatric version of Moral Distress
      Scale-Revised questionnaires. Data were analyzed using descriptive statistics, t
      test, one-way analysis of variance, and Pearson correlation coefficient.
      Participants and research context: In total, 195 pediatric nurses working at
      three selected children's specialized university hospitals in Tehran participated
      in this study. Ethical considerations: This study was evaluated and approved by
      the institutional review board of Tehran University of Medical Sciences.
      FINDINGS: The mean and standard deviation of total score of moral distress was
      106.41 +/- 61.64 within a range of 10-257. Also, the difference between the mean
      score of moral distress of the group who had not quitted their position and those
      who have quit in the past was statistically significant (p = 0.043). The
      situation that was associated with the highest moral distress was "observing
      medical students performing painful procedures on patients just to gain some
      skill." Total score of moral distress was significantly higher among male nurses
      (p = 0.014), while nurses with a master's degree experienced just a higher
      intensity of moral distress compared to those who had a bachelor's degree (p =
      0.006). CONCLUSION: Since many pediatric nurses clearly face moral distress while
      taking care of children, it is necessary to consider measures for preventing or
      decreasing situations that would lead to this distress.

PMID- 28766395
TI  - Dual loyalties: Everyday ethical problems of registered nurses and physicians in
      combat zones.
AB  - BACKGROUND: When healthcare personnel take part in military operations in combat
      zones, they experience ethical problems related to dual loyalties, that is, when
      they find themselves torn between expectations of doing caring and military
      tasks, respectively. AIM: This article aims to describe how Swedish healthcare
      personnel reason concerning everyday ethical problems related to dual loyalties
      between care and military tasks when undertaking healthcare in combat zones.
      DESIGN: Abductive qualitative design. Participants and research context:
      Individual interviews with 15 registered nurses and physicians assigned for a
      military operation in Mali. Ethical considerations: The participants signed up
      voluntarily, and requirements for informed consent and confidentiality were met.
      The research was approved by the Regional Ethics Review Board in Gothenburg (D
      no. 816-14; 24 November 2014). FINDINGS: Three main categories emerged: reasons
      for not undertaking combat duties, reasons for undertaking combat duties and
      restricted loyalty to military duties, and 14 subcategories. Reasons for not
      undertaking combat duties were that it was not in their role, not according to
      ethical codes or humanitarian law or a breach towards patients. Reasons for
      undertaking combat duties were that humanitarian law does not apply or has to be
      treated pragmatically or that it is a case of force protection. Shortage of
      resources and competence were reasons for both doing and not doing military
      tasks. Under some circumstances, they could imagine undertaking military tasks:
      when under threat, if unseen or if not needed for healthcare duties.
      DISCUSSION/CONCLUSION: These discrepant views suggest a lack of a common view on
      what is ethically acceptable or not, and therefore we suggest further normative
      discussion on how these everyday ethical problems should be interpreted in the
      light of humanitarian law and ethical codes of healthcare personnel and following
      this, further training in ethical reflection before going on military operations.

PMID- 28766396
TI  - Preventing and Alleviating Compassion Fatigue Through Self-Care: An Educational
      Workshop for Nurses.
AB  - Though various authors have refined and described the concept of compassion
      fatigue (CF), the overarching features, predisposing factors, and potential
      consequences remain relatively consistent. Available literature demonstrates that
      caregivers caring for patients who are chronically ill and/or traumatized are at
      highest risk for developing CF. Potential consequences for unmitigated CF include
      physical, emotional, and work-related consequences, all of which can have
      negative effects on the quality and safety of care and degree of engagement with
      one's employer. CF is further exacerbated by exposure to cumulative, unresolved
      stress and neglect of one's own emotional needs over time. Caregivers must be
      knowledgeable on CF's risk factors, symptoms, and management strategies to
      decrease its incidence and negative impacts. This article details the creation,
      execution, and evaluation of an evidence-based practice change project
      implemented with the goal of increasing knowledge needed to prevent, identify,
      and alleviate CF in high-risk nurses. The project involved a series of
      educational workshops containing information on CF's risk factors, symptoms, and
      consequences, with a strong emphasis on self-awareness, self-care, and stress
      management. Pre- and postknowledge tests showed a significant increase in
      knowledge was achieved via the workshops, and qualitative surveys indicated a
      high level of participant satisfaction with the program contents, format, and
      impact.

PMID- 28766397
TI  - Diagnostic accuracy of non-contrast abdominal CT scans performed as follow-up for
      patients with an established cancer diagnosis: a retrospective study.
AB  - OBJECTIVES: To determine the accuracy and non-detection rate of cancer related
      findings (CRFs) on follow-up non-contrast-enhanced CT (NECT) versus contrast
      enhanced CT (CECT) images of the abdomen in patients with a known cancer
      diagnosis. METHODS: A retrospective review of 352 consecutive CTs of the abdomen
      performed with and without IV contrast between March 2010 and October 2014 for
      follow-up of cancer was included. Two radiologists independently assessed the
      NECT portions of the studies. The reader was provided the primary cancer
      diagnosis and access to the most recent prior NECT study. The accuracy and non
      detection rates were determined by comparing our results to the archived reports
      as a gold standard. RESULTS: A total of 383 CRFs were found in the archived
      reports of the 352 abdominal CTs. The average non-detection rate for the NECTs
      compared to the CECTs was 3.0% (11.5/383) with an accuracy of 97.0% (371.5/383)
      in identifying CRFs. The most common findings missed were vascular thrombosis
      with a non-detection rate of 100%. The accuracy for non-vascular CRFs was 99.1%.
      CONCLUSION: Follow-up NECT abdomen studies are highly accurate in the detection
      of CRFs in patients with an established cancer diagnosis, except in cases where
      vascular involvement is suspected.

PMID- 28766398
TI  - Assessing joint destruction in the knees of patients with rheumatoid arthritis by
      using a semi-automated software for magnetic resonance imaging: therapeutic
      effect of methotrexate plus etanercept compared with methotrexate monotherapy.
AB  - OBJECTIVES: To evaluate the prevention of knee joint destruction and clinical
      efficacy of methotrexate (MTX) plus etanercept (ETN) compared with MTX
      monotherapy in patients with rheumatoid arthritis (RA) by using semi-automated
      software for magnetic resonance imaging (MRI) scan analysis. MATERIALS AND
      METHODS: This study enrolled patients with active moderate-to-severe RA who
      displayed an inadequate response to oral MTX at screening. Patients were assigned
      to receive either MTX plus ETN or MTX monotherapy (>=10 mg/week). The primary
      endpoint was the quantitative knee cartilage volume using our software developed
      for MRI scan analysis. RESULTS: A total of 18 female patients were enrolled in
      this study and allocated to the MTX + ETN group (n = 9) or the MTX monotherapy
      group (n = 9). At 52 weeks, the quantitative knee cartilage volume was
      significantly reduced compared with baseline in both groups (MTX plus ETN group:
      2.3 +/- 2.3 cm3; MTX monotherapy group: 2.4 +/- 1.6 cm3); however, the difference
      was not significant. CONCLUSION: The semi-automated software for MRI scan
      analysis can reveal useful and potentially clinically important information about
      the characteristics of knee joint destruction in patients with RA.

PMID- 28766399
TI  - Monitoring of learning for emotional faces: how do fine-grained categories of
      emotion influence participants' judgments of learning and beliefs about memory?
AB  - Researchers have evaluated how broad categories of emotion (i.e. positive and
      negative) influence judgments of learning (JOLs) relative to neutral items.
      Specifically, JOLs are typically higher for emotional relative to neutral items.
      The novel goal of the present research was to evaluate JOLs for fine-grained
      categories of emotion. Participants studied faces with afraid, angry, sad, or
      neutral expressions (Experiment 1) and with afraid, angry, or sad expressions
      (Experiment 2). Participants identified the expressed emotion, made a JOL for
      each, and completed a recognition test. JOLs were higher for the emotional
      relative to neutral expressions. However, JOLs were insensitive to the categories
      of negative emotion. Using a survey design in Experiment 3, participants
      demonstrated idiosyncratic beliefs about emotion. Some people believed the fine
      grained emotions were equally memorable, whereas others believed a specific
      emotion (e.g. anger) was most memorable. Thus, beliefs about emotion are nuanced,
      which has important implications for JOL theory.

PMID- 28766400
TI  - Transvenous Intravascular Ultrasound-Guided Endovascular Treatment for Chronic
      Total Occlusion of the Infrainguinal Arteries.
AB  - PURPOSE: To investigate the 1-year outcomes of transvenous intravascular
      ultrasound (IVUS)-guided endovascular therapy (EVT) for chronic total occlusion
      (CTO) of the lower extremity arteries. METHODS: Transvenous IVUS-guided EVT was
      performed in 44 patients (50 limbs) with CTO of the femoropopliteal arteries or
      tibioperoneal trunk. Treatment involved crossing a guidewire through the CTO
      under the guidance of both fluoroscopic and IVUS imaging, along with insertion of
      the IVUS catheter into a vein parallel to the target artery. Primary success
      rate, complications, and target lesion revascularization (TLR) at 12-month follow
      up were investigated. RESULTS: Successful recanalization, defined as grade 3 flow
      (Thrombolysis in Myocardial Infarction score) and no flow-limiting dissection,
      was observed in 48 (96%) limbs. Two limbs with failed recanalization had a very
      long CTO lesion from the superficial femoral artery to below the knee. A
      bidirectional approach was selected in 11 (22%) limbs. Complications at the
      access site occurred in only 2 patients. The rate of freedom from TLR at 12
      months was 77.9% (95% confidence interval 61.4 to 87.9). CONCLUSION: Transvenous
      IVUS-guided EVT is safe and can provide optimal short-term results for EVT of CTO
      in the infrainguinal arteries. IVUS-guided EVT may be one of the most effective
      treatment strategies for CTO of the femoropopliteal arteries or tibioperoneal
      trunk.

PMID- 28766401
TI  - Evaluation of a Pomegranate Peel Extract as an Alternative Means to Control Olive
      Anthracnose.
AB  - Olive anthracnose is caused by different species of Colletotrichum spp. and may
      be regarded as the most damaging disease of olive fruit worldwide, greatly
      affecting quality and quantity of the productions. A pomegranate peel extract
      (PGE) proved very effective in controlling the disease. The extract had a strong
      in vitro fungicidal activity against Colletotrichum acutatum sensu stricto, was
      very effective in both preventive and curative trials with artificially
      inoculated fruit, and induced resistance in treated olive tissues. In field
      trials, PGE was significantly more effective than copper, which is traditionally
      used to control the disease. The highest level of protection was achieved by
      applying the extract in the early ascending phase of the disease outbreaks
      because natural rots were completely inhibited with PGE at 12 g/liter and were
      reduced by 98.6 and by 93.0% on plants treated with PGE at 6 and 3 g/liter,
      respectively. Two treatments carried out 30 and 15 days before the expected
      epidemic outbreak reduced the incidence of the disease by 77.6, 57.0, and 51.8%,
      depending on the PGE concentration. The analysis of epiphytic populations showed
      a strong antimicrobial activity of PGE, which sharply reduced both fungal and
      bacterial populations. Because PGE was obtained from a natural matrix using safe
      chemicals and did not have any apparent phytotoxic effect on treated olive fruit,
      it may be regarded as a safe and effective natural antifungal preparation to
      control olive anthracnose and improve olive productions.

PMID- 28766402
TI  - Context-aware grading of quality evidences for evidence-based decision-making.
AB  - Processing huge repository of medical literature for extracting relevant and high
      quality evidences demands efficient evidence support methods. We aim at
      developing methods to automate the process of finding quality evidences from a
      plethora of literature documents and grade them according to the context (local
      condition). We propose a two-level methodology for quality recognition and
      grading of evidences. First, quality is recognized using quality recognition
      model; second, context-aware grading of evidences is accomplished. Using 10-fold
      cross-validation, the proposed quality recognition model achieved an accuracy of
      92.14 percent and improved the baseline system accuracy by about 24 percent. The
      proposed context-aware grading method graded 808 out of 1354 test evidences as
      highly beneficial for treatment purpose. This infers that around 60 percent
      evidences shall be given more importance as compared to the other 40 percent
      evidences. The inclusion of context in recommendation of evidence makes the
      process of evidence-based decision-making "situation-aware."

PMID- 28766403
TI  - Community Evaluation of the National Diabetes Education Program's Diabetes
      HealthSense Website.
AB  - Purpose The purpose of this study was to assess the impact of Diabetes
      HealthSense on knowledge, attitudes, and behavior changes that prevent, delay, or
      manage diabetes among people at risk (PAR) for diabetes and people with diabetes
      (PWD). Methods Using a 2-group pretest-posttest design, 15 community sites were
      randomly assigned to either an intervention or comparison group. Intervention
      participants attended a group education session with a diabetes educator,
      followed by 4 weeks of independent use of the Diabetes HealthSense website. The
      comparison group received no intervention. A total of 311 adults (n = 135
      intervention, n = 176 comparison) completed both a pretest and posttest. Outcome
      measures examined changes in self-reported knowledge, self-efficacy, and
      behaviors that support diabetes prevention or management. Results Statistically
      significant within-group pretest to posttest changes were found for almost all
      outcome measures in the intervention group, with no significant changes in the
      comparison group. Significant between-group differences were also found for
      almost all outcome measures at posttest, with the intervention group having more
      positive outcomes than the comparison group. Conclusions Patient referral to
      online tools is considered one key component of initial and ongoing diabetes self
      management education and support (DSME/S) and is recommended as a way to enhance
      and extend the reach of in-person diabetes education. Positive outcomes were
      found for PWD/PAR who used Diabetes HealthSense following a guided education
      session. Study results suggested that with guided exploration, Diabetes
      HealthSense provided a valuable tool for educators to use with patients to
      support and extend the reach of DSME/S.

PMID- 28766404
TI  - Drug-Eluting Biopsy Needle as a Novel Strategy for Antimicrobial Prophylaxis in
      Transrectal Prostate Biopsy.
AB  - OBJECTIVES: To preclinically evaluate drug-eluting biopsy needles (patent pending
      WO2016118026) as a new potential way of antimicrobial prophylaxis for transrectal
      prostate biopsy. METHODS: Twenty steel biopsy needles have been coated with
      polyvinyl alcohol, ciprofloxacin, and amikacin. Modified biopsy needles have been
      randomly divided into 3 groups (1:2:1 ratio). Needles from group I were immersed
      for 30 minutes in dedicated test tubes containing saline. Needles from group II
      were immersed (one by one) for 5 seconds in a set of 12 test tubes containing
      saline. Then, each solution was analyzed using high-performance liquid
      chromatography. The results were compared with the susceptibility break points
      for Escherichia coli. Group III was incubated with E coli strains on Mueller
      Hinton plate and then the bacterial inhibition zones surrounding needles were
      measured. RESULTS: The average concentration of antibiotics eluted from needles
      (group I) was 361.98 +/- 15.36 ug/mL for amikacin and 63.87 +/- 5.95 ug/mL for
      ciprofloxacin. The chromatographic analysis revealed the gradual release of both
      antibiotics from needles (group II). The concentration of amikacin released from
      needles exceeded the break-point value from first to ninth immersion.
      Ciprofloxacin concentration was higher than break-point value in all immersions.
      The average bacterial inhibition zone minor axis was 42 +/- 5.7 mm (group III).
      CONCLUSIONS: The use of drug-eluting biopsy needle could be a new potential way
      of antimicrobial prophylaxis for transrectal prostate biopsy. This study
      confirmed its biological activity as well as the gradual release of antibiotics
      from its surface. Confirmation of its preventive role, in terms of infectious
      complications after transrectal prostate biopsy, has to be evaluated in a
      clinical trial.

PMID- 28766405
TI  - Chronic pain as a human rights issue: setting an agenda for preventative action.
AB  - BACKGROUND: Historically, chronic pain has been viewed primarily as a medical
      issue, and research has been focused on the individual and predominantly on pain
      sufferers in high-income countries. OBJECTIVES: This article argues the need for
      a broader understanding of the context of chronic pain and its complex
      aetiologies and maintenance. It is suggested that the interaction between chronic
      pain and social context has been inadequately explored. METHODS: A single case
      study is used of a man living in a violent urban environment in South Africa
      accessing a pain clinic at a tertiary hospital. Following the case-study
      approach, as used in the chronic traumatic stress field by Kaminer et al., the
      case material is utilised to develop an argument for a new research agenda.
      RESULTS: Analysis of the case material demonstrates the complex interplay between
      bodily and psychological experiences, with chronic pain being contextually
      maintained and exacerbated by very difficult life circumstances, ongoing
      violence, and marginalisation. CONCLUSIONS: It is suggested that a research
      agenda be developed which explores the links between chronic pain and ongoing
      chronic traumatisation in contexts of continuous violence, oppression, and
      disempowerment - common features of much of the contemporary majority world.

PMID- 28766406
TI  - Molecular dynamics simulations of Hsp40 J-domain mutants identifies disruption of
      the critical HPD-motif as the key factor for impaired curing in vivo of the yeast
      prion [URE3].
AB  - Genetic screens using Saccharomyces cerevisiae have identified an array of Hsp40
      (Ydj1p) J-domain mutants that are impaired in the ability to cure the yeast
      [URE3] prion through disrupting functional interactions with Hsp70. However,
      biochemical analysis of some of these Hsp40 J-domain mutants has so far failed to
      provide major insight into the specific functional changes in Hsp40-Hsp70
      interactions. To explore the detailed structural and dynamic properties of the
      Hsp40 J-domain, 20 ns molecular dynamic simulations of 4 mutants (D9A, D36A,
      A30T, and F45S) and wild-type J-domain were performed, followed by Hsp70 docking
      simulations. Results demonstrated that although the Hsp70 interaction mechanism
      of the mutants may vary, the major structural change was targeted to the critical
      HPD motif of the J-domain. Our computational analysis fits well with previous
      yeast genetics studies regarding highlighting the importance of J-domain function
      in prion propagation. During the molecular dynamics simulations several important
      residues were identified and predicted to play an essential role in J-domain
      structure. Among these residues, Y26 and F45 were confirmed, using both in silico
      and in vivo methods, as being critical for Ydj1p function.

PMID- 28766407
TI  - Anticonvulsant effects of thiamine on pentylenetetrazole-induced seizure in mice.
AB  - OBJECTIVES: Thiamine serves as a cofactor for several enzymes involved in brain
      function and neurotransmitters biosynthesis. Thiamine-dependent enzymes are
      important for oxidant stress defenses. Several studies have reported that
      thiamine deficiency in the central nervous system reduces seizure threshold. The
      present study was designed to investigate the effect of acute and chronic
      administration of thiamine alone and in combination with sub-effective dose of
      diazepam on pentylenetetrazole (PTZ)-induced tonic-clonic seizures in mice.
      METHODS: Animals were randomly divided into control and experimental groups. In
      experimental groups, thiamine (50, 100, and 200 mg/kg i.p.) was administered
      acutely or chronically (once a day, for 14 days). Slow intravenous infusion of
      PTZ (5 mg/ml) by infusion pump with a constant rate (0.3 ml/min) was used to
      induce clonic and tonic seizures. RESULTS: Acute injection of thiamine (50, 100,
      and 200 mg/kg i.p.) did not increase seizure threshold significantly, but chronic
      treatment with thiamine (200 mg/kg i.p.) increases the clonic and tonic seizure
      threshold. Moreover, the combination of sub-effective dose of thiamine (100
      mg/kg) and diazepam (0.1 mg/kg) significantly increased seizure threshold and
      enhanced the anticonvulsant effect of diazepam at ineffective dose (0.1 mg/kg).
      DISCUSSION: Our results suggest that thiamine can be considered as a potential
      add-on treatment in deficient and non-deficient thiamine epileptic patients. Co
      administration of this vitamin with classic antiepileptics to decrease the
      required doses of regular drugs may be recommended. Nevertheless, more well
      designed studies may be executed to provide further accurate information.

PMID- 28766408
TI  - Baseball pitching accuracy: an examination of various parameters when evaluating
      pitch locations.
AB  - This study evaluated baseball pitching accuracy using a variety of parameters to
      quantify pitching errors and analysed the validity of the accuracy measurements
      by comparing the outcomes of two small groups of pitchers. Several professional
      (n = 5) and high school (n = 8) pitchers threw 30 pitches each, including 20
      fastballs and 10 breaking balls. To assess pitching accuracy, pitch locations
      relative to the catcher's mitt (as the target) were evaluated with various
      parameters, including major/minor radius, an area of 95% confidence ellipse,
      absolute error, constant error and pitch location trajectory. Compared to the
      high school pitchers, the professional pitchers exhibited shorter major and minor
      radii in their 20 fastball pitches (p < 0.05), more accurate control in the
      lateral direction (p < 0.05), and shorter pitch location trajectories (p < 0.05).
      The evaluation methods presented in this study can objectively assess pitching
      accuracy and may thus provide useful coaching feedback with visual information.

PMID- 28766410
TI  - RCN guidance on responding to unexpected incidents or emergencies.
AB  - Essential facts Four terror attacks and the devastating Grenfell Tower fire in
      the space of four months have sadly demonstrated the dangers posed to all
      involved in unexpected events or emergencies.

PMID- 28766411
TI  - Nursing in the Middle East.
AB  - International assignments are a great way for UK nurses and other healthcare
      professionals to broaden their experience and work in some of the world's most
      modern hospitals.

PMID- 28766409
TI  - Phase 1 healthy volunteer willingness to participate and enrollment preferences.
AB  - BACKGROUND/AIMS: Healthy volunteers in phase 1 clinical trials contribute to the
      development of safe drugs and other biologics and accept risks and burdens
      without anticipated health benefits from participation. Although emerging data
      have shown that healthy volunteers are influenced by risk, some still worry that
      financial incentives lead them to take on unreasonable risk. Yet little is known
      about healthy volunteers' preferences and how they make choices about enrolling
      in research studies. METHODS: We surveyed 654 healthy volunteers at the end of
      their participation in a phase 1 Pfizer trial in the United States, Belgium, and
      Singapore to examine their reported willingness to enroll in studies of different
      types, with various procedures, and with possible side-effects. RESULTS: The
      majority of respondents were willing to join many kinds of studies, but fewer
      were willing to participate in first-in-human vaccine studies or studies of
      psychiatric drugs than in other study types. With regard to procedures, a
      substantial proportion were unwilling to participate in studies that involved
      invasive procedures, such as a lumbar puncture (45.4%) and bone marrow biopsy
      (42.3%), but willing to participate in studies with less invasive procedures such
      as a computed tomography scan of the heart (86.8%), magnetic resonance imaging
      (87.4%), and skin allergy testing (86.8%). Although there was some variation by
      gender and region, the majority were willing to participate in studies with side
      effects like pain (80%) or nausea and vomiting (64%), but only a minority were
      willing to join if the research drug would result in their having a one in a
      million chance of death (34.4%), a small chance of kidney damage (16.7%), or
      influence how their mind works (23.2%; Figure 4). CONCLUSION: Our results suggest
      that healthy volunteers are willing to participate in a wide range of types of
      phase 1 clinical trials, and express preferences for low risk and familiar
      studies and study procedures, preferences which are partially affected by offers
      of payment.

PMID- 28766412
TI  - RCN braced for strike ballot if ministers do not lift pay cap.
AB  - The RCN will ballot members over industrial action later this year if the
      government refuses to scrap the NHS pay cap, the college's general secretary
      warned.

PMID- 28766413
TI  - Laughing and innovating.
AB  - After qualifying as a nurse at St Mary's Hospital in London in 1988, Joanna James
      spent 20 years working in emergency departments. She co-developed and ran a
      successful education programme around the needs of refugees and survivors of
      torture. In 2008 she changed direction and started working on improving services
      for people with dementia in hospital. She is now lead nurse for dementia at
      Imperial College Healthcare NHS Trust in London.

PMID- 28766415
TI  - Ministers have the power to avert this 'perfect storm' - and strike action.
AB  - Nursing is facing a 'perfect storm', according to the RCN. Rising vacancies,
      shrinking nurse numbers, increasing pressure of work, falling pay - and that's
      before staff numbers feel the full impact of Brexit.

PMID- 28766416
TI  - Action against human trafficking and slavery.
AB  - Nursing student Louise Cahill was instrumental in developing a tool that helps
      health professionals identify and respond to victims of modern slavery and human
      trafficking.

PMID- 28766417
TI  - 'Poor workforce planning' behind Scottish pressures.
AB  - Nurses and other NHS staff in Scotland are facing increasing workload pressures
      due to a lack of workforce planning by government, according to a new report.

PMID- 28766419
TI  - Mental health nurse helps me feel empowered and independent.
AB  - Nadine and I met during my first admission to the psychiatric ward at Dr Gray's
      Hospital, Elgin, Moray, in 2003. She was my named nurse at the time, and has been
      my community mental health nurse for the past three years.

PMID- 28766418
TI  - Benefits of, and barriers to, family-witnessed resuscitation in practice.
AB  - This article, discussing family-witnessed resuscitation, is the first in a series
      providing nurses with information about essential aspects of critical care.
      Family-witnessed resuscitation is not common practice in healthcare settings,
      despite its well-documented benefits. Lack of implementation arises because of
      fear and anxiety among healthcare practitioners about the potential negative
      consequences for the patient, the family and themselves. However, research has
      suggested that addressing these concerns could positively affect practice and
      increase the number of cases of family-witnessed resuscitation. This article
      discusses the potential benefits of, and barriers to, family-witnessed
      resuscitation and how the practice could become increasingly adopted in
      healthcare settings.

PMID- 28766422
TI  - Vitamin D deficiency in pregnancy linked to child's motor skills.
AB  - Pregnant women with a vitamin D deficiency are more likely to have children with
      poorer motor development such as the ability to jump, a study has found.

PMID- 28766423
TI  - Implantable cardioverter defibrillators.
AB  - What was the nature of the CPD activity, practice-related feedback and/or event
      and/or experience in your practice? The article discussed the factors associated
      with health-related quality of life in patients with an implantable cardioverter
      defibrillator (ICD). In my practice, I discuss ICDs regularly with patients who
      have these devices and with those who may require them imminently. The article
      provided information that will enable me to ensure these discussions are person
      centred.

PMID- 28766425
TI  - Trust invests L16 million in accommodation to become more attractive to nursing
      staff.
AB  - Work has begun on a L16.4 million accommodation block at a hospital in
      Lincolnshire in a bid to recruit and retain nurses.

PMID- 28766424
TI  - 'You made me feel human again'.
AB  - In my third year of training I had a poignant experience that I will never
      forget. I was on placement in the intensive care unit when I met a patient, who I
      will call Emily, who had been admitted following a suicide attempt.

PMID- 28766426
TI  - NMC English language requirement too high.
AB  - The English language requirement by the NMC is far higher than that for UK
      universities, and it is hurting nursing and patient outcomes.

PMID- 28766427
TI  - Nursing's language barrier.
AB  - There should be no compromise on the English language test for overseas nurses.
      Their skill level is not in question, but it is no good if they cannot understand
      what patients are saying, or patients cannot understand them.

PMID- 28766428
TI  - Everyone needs the health benefits of being outdoors.
AB  - A study by researchers at the University of Warwick has shown that for many older
      people in care homes it takes a great effort to get outdoors. This isn't due to a
      lack of will but rather the environment they are living in and the restrictions
      placed on them, which range from needing permission to go outside to inadequate
      seating in gardens.

PMID- 28766430
TI  - Tall men 'more at risk from aggressive prostate cancer'.
AB  - Tall men are at greater risk of dying from aggressive prostate cancer, research
      has shown.

PMID- 28766429
TI  - Student life - A playful way to learn.
AB  - Students do not always like speaking in class. The more confident talkers can
      sometimes overshadow more reserved students, who prefer to let others talk while
      they think things through.

PMID- 28766431
TI  - Vaccine shows promise.
AB  - A vaccine to protect against gonorrhoea offers hope in the fight against drug
      resistant sexually transmitted infections, according to a study of 14,000 people.

PMID- 28766433
TI  - Holocaust survivors found to have greater cancer risk.
AB  - Researchers from the Chaim Sheba Medical Center in Israel studied more than
      152,000 Holocaust survivors over 45 years.

PMID- 28766432
TI  - Role of effective nurse-patient relationships in enhancing patient safety.
AB  - Ensuring and maintaining patient safety is an essential aspect of care provision.
      Safety is a multidimensional concept, which incorporates interrelated elements
      such as physical and psychosocial safety. An effective nurse-patient relationship
      should ensure that these elements are considered when planning and providing
      care. This article discusses the importance of an effective nurse-patient
      relationship, as well as healthcare environments and working practices that
      promote safety, thus ensuring optimal patient care.

PMID- 28766434
TI  - Little things can make a big difference.
AB  - We had guests staying for the weekend recently and found ourselves passionately
      discussing the delicate topic of morning ablutions.

PMID- 28766435
TI  - Dying homeless receiving little palliative care, study finds.
AB  - Homeless people are dying in unsupported and unacceptable situations with
      inadequate access to palliative care services, a study has found.

PMID- 28766436
TI  - How to perform nasal douching.
AB  - Rationale and key points This article provides information on nasal douching,
      which nurses can use to advise patients on how to perform this procedure. It
      explains how to prepare and use a home-made solution for nasal douching, and
      discusses the various products available that can assist patients in undertaking
      this procedure. " Nasal douching, also known as nasal washout, irrigation or
      lavage, is recommended to clear mucus and allergens from the nose for people with
      rhinitis or rhinosinusitis. It is also recommended following nasal surgery to
      cleanse and aid healing inside the nose. " Nasal douching can be used as a
      baseline preparation treatment or alone to reduce the symptoms of sinonasal
      disease and/or allergy. It can also be performed 10-20 minutes before using a
      corticosteroid nasal spray, which increases the efficacy of this treatment. "
      Saline solutions used for nasal douching can be home-made or ready-mixed
      products. While it may be easier to use ready-mixed products to perform the
      procedure, they can be expensive. A balanced isotonic saline solution made at
      home using common household ingredients is considered equally safe and effective.
      Reflective activity 'How to' articles can help update your practice and ensure it
      remains evidence-based. Apply this article to your practice. Reflect on and write
      a short account of: 1. How you could use this article to enable patients to
      understand the benefits of nasal douching. 2. How you can support patients to
      perform nasal douching on a daily basis, to maximise the effectiveness of their
      treatment.

PMID- 28766438
TI  - 'Don't forget lessons of Mid Staffs failings'.
AB  - Nurses and other NHS staff have become 'shock absorbers' for a health service
      under chronic strain, according to a report.

PMID- 28766439
TI  - Action plan aims to boost practice nurse workforce.
AB  - A ten-point action plan to boost the general practice nursing (GPN) workforce has
      been published by England's chief nurse.

PMID- 28766440
TI  - More than a golden hello.
AB  - Golden hellos for nurses are okay, but won't improve retention of staff. As soon
      as new recruits learn how short-staffed wards are and how few trained nurses are
      on shifts, they won't stay long anyway.

PMID- 28766441
TI  - Prison - no place for older people.
AB  - Prisons and probation ombudsman Nigel Newcomen has called for a national strategy
      to address the healthcare needs of older people in prison. His report should be
      welcomed - it focuses attention on a group of people who are all too easily
      overlooked in our society. The bad news is, the report is a depressing read.
      Prisons designed for young men are struggling to cope with people in their
      seventies and eighties who may have dementia or need palliative care.

PMID- 28766442
TI  - Copyright query.
AB  - If you don't own the copyright to the chart, you are not entitled to payment when
      it is reproduced. Factors that need to be considered to determine whether you own
      the rights to the chart include whether it was designed as part of your working
      duties, whether you used other charts to help you design the new one, and what is
      stated in your contract.

PMID- 28766443
TI  - Guidance on supporting traumatised children launched.
AB  - New guidance has been launched to help health visitors support children and
      families coping with a traumatic event.

PMID- 28766447
TI  - Government claims vs reality.
AB  - The public must be made aware that government claims such as 'there are more
      nurses than ever' do not match reality.

PMID- 28766445
TI  - Revalidation fosters a culture of reflection and good practice.
AB  - When we launched revalidation in April 2016 it represented one of the most
      significant changes to nursing and midwifery in a generation.

PMID- 28766448
TI  - Brexit not to blame.
AB  - I wish people would stop blaming Brexit for threatening the future of the NHS.

PMID- 28766449
TI  - Revalidation is a positive.
AB  - I revalidated last year and found it a positive experience. It helped to look
      back on the things I had achieved, and it wasn't too onerous either.

PMID- 28766451
TI  - Non-Alzheimer's and Atypical Dementia Geschwind Michael D and Belkoura Caroline
      Racine (Eds) Non-Alzheimer's and Atypical Dementia 232pp L94.99 Wiley-Blackwell
      9781444336245 144433624X [Formula: see text].
AB  - This overview of atypical dementia was written specifically for multidisciplinary
      teams. Its case studies are helpful for translating information from the page to
      the patient, and the references at the end of each chapter are useful for further
      reading.

PMID- 28766450
TI  - Long-awaited changes set to speed up fitness to practise cases.
AB  - Changes to fitness to practise (FtP) referral processes for nurses and midwives,
      aimed at speeding up the system, came into effect on 28 July.

PMID- 28766452
TI  - Introducing Mental Health: A Practical Guide (Second edition) Kinsella Caroline
      Kinsella Connor Introducing Mental Health: A Practical Guide (Second edition)
      200pp L16.99 Jessica Kingsley Publishers 9781849055963 1849055963 [Formula: see
      text].
AB  - The authors have done an excellent job of bringing this edition up to date.
      Readers can either digest it from cover to cover or dip in and out, selecting
      elements relevant to them.

PMID- 28766453
TI  - How to Survive Your Nursing or Midwifery Course Gribben Monica McLellan Stephen
      McGirr Debbie Chenery-Morris Sam How to Survive Your Nursing or Midwifery Course
      296pp L12.99 Sage 9781473969230 1473969239 [Formula: see text].
AB  - This book is designed to help nursing students and midwives juggle the competing
      demands of work, study and life.

PMID- 28766454
TI  - Readers' panel - Pay or working conditions: which is more important?
AB  - Our experts consider a hot topic of the day.

PMID- 28766455
TI  - CPR teaching pays off, as retired nurse is saved by his first aid course
      students.
AB  - The last thing retired nurse David Knowles expected when he began a demonstration
      of cardiopulmonary resuscitation (CPR) was that his trainees would put their
      learning into practice immediately - on him.

PMID- 28766456
TI  - Creating a stronger voice for nursing in Zambia.
AB  - Jennifer Munsaka is the first to admit that her organisation didn't always get
      the most positive reception from government ministers or hospital management. The
      director of policy, programmes and professional affairs at the Zambia Union of
      Nurses Organization (ZUNO) was aware it was perceived as fighting for nurses'
      rights rather than leading on professional matters, such as improving patient
      safety.

PMID- 28766457
TI  - Speak out if you see patients being treated insensitively.
AB  - I'm often told not to 'interfere', so have learned to rein myself in. But
      sometimes....

PMID- 28766458
TI  - Making the grade: The English language test dilemma.
AB  - Hayley Purcell admits she felt apprehensive about receiving the results of a test
      designed to ensure she was proficient in English. After months of preparation, at
      a cost of several hundred pounds, the Australian had achieved a very good result
      overall, with 7.5 out of a possible nine in the International English Language
      Testing System (IELTS).

PMID- 28766459
TI  - Subjective cognitive complaints and neuropsychological performance in former
      smokers with and without chronic obstructive pulmonary disease.
AB  - OBJECTIVE: This study examined the association of perceived cognitive
      difficulties with objective cognitive performance in former smokers. We
      hypothesized that greater perceived cognitive difficulties would be associated
      with poorer performance on objective executive and memory tasks. METHOD:
      Participants were 95 former smokers recruited from the COPDGene study. They
      completed questionnaires (including the Cognitive Difficulties Scale [CDS] and
      the Hospital Anxiety and Depression Scale [HADS]), neuropsychological assessment,
      and pulmonary function testing. Pearson correlations and t-tests were conducted
      to examine the bivariate association of the CDS (total score and subscales for
      attention/concentration, praxis, delayed recall, orientation for persons,
      temporal orientation, and prospective memory) with each domain of objective
      cognitive functioning (memory recall, executive functioning/processing speed,
      visuospatial processing, and language). Simultaneous multiple linear regression
      was used to further examine all statistically significant bivariate associations.
      The following covariates were included in all regression models: age, sex, pack
      years, premorbid functioning (WRAT-IV Reading), HADS total score, and chronic
      obstructive pulmonary disease (COPD) status (yes/no based on GOLD criteria).
      RESULTS: In regression models, greater perceived cognitive difficulties overall
      (using CDS total score) were associated with poorer performance on executive
      functioning/processing speed tasks (b = -0.07, SE = 0.03, p = .037). Greater
      perceived cognitive difficulties on the CDS praxis subscale were associated with
      poorer performance on executive functioning/processing speed tasks (b = -3.65, SE
      = 1.25, p = .005), memory recall tasks (b = -4.60, SE = 1.75, p = .010), and
      language tasks (b = -3.89, SE = 1.39, p = .006). CONCLUSIONS: Clinicians should
      be aware that cognitive complaints may be indicative of problems with the
      executive functioning/processing speed and memory of former smokers with and
      without COPD.

PMID- 28766460
TI  - Revealing Oft-cited but Unpublished Papers of Colin Pittendrigh and Coworkers.
AB  - Among the scientific resources that Colin Pittendrigh passed on to his colleagues
      after his death in 1996 were two unpublished papers. These manuscripts, developed
      first in the mid-1960s and continually updated and refined through the late
      1970s, centered on the development and experimental exploration of a model of
      circadian entrainment combining aspects of the well-known parametric (continuous)
      and nonparametric (discrete) models of entrainment. These texts reveal the
      experimental work surrounding Pittendrigh's determination of the limits of
      entrainment and the explanation of the bistability phenomenon. These manuscripts
      are being made publicly available in their final format (February 1978) as
      supplementary material to this introduction.

PMID- 28766461
TI  - Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting
      multiple sclerosis associates with lower miRNA-21 levels and concomitant up
      regulation of its target genes.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the
      central nervous system caused by genetic and environmental factors. DNA
      methylation, an epigenetic mechanism that controls genome activity, may provide a
      link between genetic and environmental risk factors. OBJECTIVE: We sought to
      identify DNA methylation changes in CD4+ T cells in patients with relapsing
      remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls
      (HC). METHODS: We performed DNA methylation analysis in CD4+ T cells from RR-MS,
      SP-MS, and HC and associated identified changes with the nearby risk allele,
      smoking, age, and gene expression. RESULTS: We observed significant methylation
      differences in the VMP1/MIR21 locus, with RR-MS displaying higher methylation
      compared to SP-MS and HC. VMP1/MIR21 methylation did not correlate with a known
      MS risk variant in VMP1 or smoking but displayed a significant negative
      correlation with age and the levels of mature miR-21 in CD4+ T cells.
      Accordingly, RR-MS displayed lower levels of miR-21 compared to SP-MS, which
      might reflect differences in age between the groups, and healthy individuals and
      a significant enrichment of up-regulated miR-21 target genes. CONCLUSION: Disease
      related changes in epigenetic marking of MIR21 in RR-MS lead to differences in
      miR-21 expression with a consequence on miR-21 target genes.

PMID- 28766462
TI  - Visual Correlates of Fitness to Drive in Adults With Multiple Sclerosis.
AB  - The impact of visual and visual-cognitive impairments on fitness to drive in
      persons with multiple sclerosis (PwMS) are not well studied. We quantified visual
      correlates of fitness to drive in 30 PwMS. PwMS completed visual ability and
      visual attention assessments, and a standardized on-road assessment, and were
      compared with 145 older volunteer drivers. PwMS (vs. older volunteer drivers)
      made more total ( W = 12,139, p = .03) and critical driving errors (predictive of
      crashes) in adjustment to stimuli ( W = 11,352, p < .0001), vehicle positioning (
      W = 11,449, p < .0001), and wide lane turns ( W = 9,932, p < .0001). PwMS who
      failed (vs. passed) made more total ( W = 325, p = .04), adjustment to stimuli (
      W = 321.5, p = .02), and gap acceptance errors ( W = 333, p = .03). For PwMS,
      adjustment to stimuli errors moderately correlated with visual acuity (rho = .50,
      p = .006), and gap acceptance errors moderately correlated with visual processing
      speed (rho = .40, p = .03). Visual-cognitive impairments may be indicative of
      critical driving errors and help identify PwMS at-risk for fitness to drive.

PMID- 28766463
TI  - Long-term effects of directed forgetting.
AB  - The intention to forget reduces the accessibility of information in memory, which
      is commonly explained with temporary retrieval difficulties. Long-term effects
      have rarely been studied, and results are inconsistent. The present study re
      assessed the long-term effects of directed forgetting (DF). Participants encoded
      a first list of items (L1), and were then instructed to forget or to remember
      this list. Immediately afterwards, all participants were presented with a second
      list to remember. In Experiment 1, memory for L1 and L2 was assessed after a 24-h
      delay. The forget cue reduced the number of items that were recalled from L1.
      Experiment 2 implemented a 12-h delay between encoding and test that was either
      filled with day-time wakefulness or night-time sleep. Replicating the findings of
      Exp. 1, recall of L1 was reduced in the forget in comparison to the remember
      condition. Sleep in comparison to wakefulness significantly strengthened L1
      memory in the remember group only. Taken together, the present study shows that
      the intention to forget can have long-lasting consequences. This suggests that
      different mechanisms underlie the short- and long-term effects of DF, with long
      term effects potentially reflecting the preferential consolidation of information
      that has been identified as important during encoding.

PMID- 28766464
TI  - Stigma and illness uncertainty: adding to the burden of sickle cell disease.
AB  - BACKGROUND: Persons with sickle cell disease (SCD) experience multiple medical
      and physical complications; the disease also has numerous effects on their social
      and emotional well-being. We hypothesized that adults with SCD in Jamaica
      experience moderate levels of stigma and illness uncertainty and that these
      experiences may be associated with socio-demographic factors, such as gender,
      educational status and economic status. METHODS: We surveyed 101 adults with SCD
      (54.5% female; mean age 31.6 +/- 10.4 years; 72.2% homozygous SCD) using the
      Stigma in Sickle Cell Disease Scale (Adult), Mishel Uncertainty in Illness Scale
      (Adult) and a Socio-Demographic questionnaire. RESULTS: The mean stigma score was
      33.6 +/- 21.6 (range: 2-91) with no significant difference between males and
      females (32.3 +/- 21.3 vs. 34.7 +/- 21.9; p-value = 0.58). Illness uncertainty
      was greater in females than in males, though not statistically significant, (88.7
      +/- 13.5 vs. 82.6 +/- 19.2; p-value: 0.07). Stigma and uncertainty had a
      significant positive correlation (r: 0.31; p-value: 0.01). In an age and sex
      controlled model, stigma scores were lower with higher numbers of household items
      (coef: -2.26; p-value: 0.001) and higher in those living in greater crowding
      (coef: 7.89; p-value: 0.002). Illness uncertainty was higher in females (coef:
      6.94; p-value: 0.02) and lower with tertiary as compared with primary education
      (coef: -16.68; p-value: 0.03). CONCLUSION: The study highlights socioeconomic
      factors to be significant to the stigma and illness uncertainty experiences in
      SCD. Efforts by healthcare workers to reduce patient illness uncertainty may have
      additional impact, reducing their stigma.

PMID- 28766465
TI  - The dynamic of tuberculosis case finding in the era of the public-private mix
      strategy for tuberculosis control in Central Java, Indonesia.
AB  - BACKGROUND: The public-private mix (PPM) strategy has strengthened tuberculosis
      care and control in many countries. Indonesia, a country with a high tuberculosis
      burden, has a low tuberculosis case detection rate (CDR), despite PPM
      implementation in 2003. The PPM in Indonesia involves primary healthcare centers,
      hospitals, and specialized chest clinics. The long-term impact of the strategy is
      unknown. OBJECTIVE: We aimed to explore the case detection achievements of the
      tuberculosis program since PPM implementation in Central Java in 2003. METHODS:
      This retrospective cohort study covered the period 1 January 2000 to 31 December
      2014. The data from tuberculosis patients treated in all health facilities in
      Central Java implementing directly observed treatment short-course, recorded via
      a standardized form, were analyzed after being validated by the Office of Health
      of Central Java Province. We evaluated the CDR, case notification rate, and total
      number of cases, using linear regression to analyze the temporal trends of those
      indicators in the phases of PPM implementation. RESULTS: The CDR increased during
      the initial phase (2000-2005), decreased during the mid-phase (2006-2009), and
      increased slightly during the late phase (2010-2014), ranging from 13 to 61.72.
      These trends were observed despite a steady increase in the number of
      participating healthcare facilities. The regression analysis showed that the CDR
      of referral institutions contributed the most to the total CDR of Central Java
      Province. Many of the smear-negative tuberculosis cases recorded at primary
      healthcare centers may have been smear positive; this probable misclassification
      could have been partially avoided if more specific and sensitive diagnostic tools
      were available. CONCLUSIONS: The CDR remains below the national target (70%).
      Early awareness of a negative trend in certain program indicators is important to
      ensure program sustainability. Careful observation of the indicator pattern will
      secure the long-term success of the program.

PMID- 28766466
TI  - An analysis of community perceptions of mosquito-borne disease control and
      prevention in Sint Eustatius, Caribbean Netherlands.
AB  - BACKGROUND: In the Caribbean, mosquito-borne diseases are a public health threat.
      In Sint Eustatius, dengue, Chikungunya and Zika are now endemic. To control and
      prevent mosquito-borne diseases, the Sint Eustatius Public Health Department
      relies on the community to assist with the control of Aedes aegypti mosquito.
      Unfortunately, community based interventions are not always simple, as community
      perceptions and responses shape actions and influence behavioural responses
      Objective: The aim of this study was to determine how the Sint Eustatius
      population perceives the Aedes aegypti mosquito, mosquito-borne diseases and
      prevention and control measures and hypothesized that increased knowledge of the
      virus, vector, control and prevention should result in a lower AQ1 prevalence and
      incidence of mosquito-borne diseases. METHODS: This study was conducted in Sint
      Eustatius island in the Eastern Caribbean. We combined qualitative and
      quantitative designs. We conducted interviews and focus groups discussions among
      community member and health professional in 2013 and 2015. We also conducted
      cross-sectional survey to assess local knowledge on the vector, virus, and
      control and prevention. RESULTS: The population is knowledgeable; (c)however,
      mosquito-borne diseases are not the highest health priority. While local
      knowledge is sometimes put into action, it happens on the 20 household/individual
      level as opposed to the community level. After the 2014 CHIK outbreak, there was
      an increase in knowledge about mosquito control and mosquito-borne diseases.
      DISCUSSION: In the context of Sint Eustatius, when controlling the Aedes
      population it may be a strategic option to focus on the household level rather
      than the community and build collaborations with households by supporting them
      when they actively practice mosquito 25 control. To further increase the level of
      knowledge on the significance of mosquito-borne diseases, it may also be an
      option to contextualize the issue of the virus, vector, prevention and control
      into a broader context. CONCLUSION: As evidenced by the increasing number of
      mosquito-borne diseases on the island, it appears that knowledge amongst the lay
      community may not be transferred into 30 action. This may be attributed to the
      perception of the Sint Eustatius populations that mosquitoes and the viruses they
      carry are not a high priority in comparison to other health concerns.

PMID- 28766467
TI  - Sleep and mood in older adults: coinciding changes in insomnia and depression
      symptoms.
AB  - The aim of this analysis was to test if changes in insomnia symptoms and global
      sleep quality are associated with coinciding changes in depressed mood among
      older adults. We report on results yielded from secondary analysis of
      longitudinal data from a clinical trial of older adults (N = 49) aged 55 to 80
      years who reported at least moderate levels of sleep problems. All measures were
      collected at baseline and after the trial ten weeks later. We computed change
      scores for two separate measures of disturbed sleep, the Athens Insomnia Scale
      (AIS) and the Pittsburgh Sleep Quality Index (PSQI), and tested their association
      with change in depressed mood (Beck Depression Inventory-II; BDI-II) in two
      separate linear regression models adjusted for biological covariates related to
      sleep (sex, age, body mass index, and NF-kappaB as a biological marker previously
      correlated with insomnia and depression). Change in AIS scores was associated
      with change in BDI-II scores (beta = 0.38, p < 0.01). Change in PSQI scores was
      not significantly associated with change in BDI-II scores (beta = 0.17, p =
      0.26). Our findings suggest that improvements over ten weeks in insomnia symptoms
      rather than global sleep quality coincide with improvement in depressed mood
      among older adults.

PMID- 28766468
TI  - Expectations and limitations of ovarian tissue transplantation.
AB  - Constant progress in the diagnosis and treatment of cancer disease has increased
      the number and prognosis of cancer survivors. However, the toxic effects of
      chemotherapy and radiotherapy on ovarian function have resulted in premature
      ovarian failure. Patients are, therefore, still expecting methods to be developed
      to preserve their fertility successfully. Several potential options are available
      to preserve fertility in patients who face premature ovarian failure, including
      immature or mature oocyte and embryo cryopreservation. However, for children or
      prepubertal women needing immediate chemotherapy, cryopreservation of ovarian
      tissue is the only alternative. The ultimate aim of this strategy is to implant
      ovarian tissue into the pelvic cavity (orthotopic site) or in a heterotopic site
      once oncological treatment is completed and the patient is disease free.
      Transplantation of ovarian tissue with sufficiently large numbers of follicles
      could potentially restore endocrine function and allow multiple cycles for
      conception. However, the success of ovarian tissue transplantation still has
      multiple challenges, such as the low number of follicles in the graft that may
      affect their longevity as well as the survival of the tissue during ex vivo
      processing and subsequent transplantation. Therefore, this review aims to
      summarize the achievements of ovary grafting and the potential techniques that
      have been developed to improve ovarian graft survival.

PMID- 28766469
TI  - The forsaking of the clinical EEG by psychiatry: how justified?
AB  - Despite decades of publications attesting to the role of the clinical EEG in
      diagnosing and managing psychiatric disorders, the procedure remains highly
      underutilized in the practice of psychiatry. The visually inspected EEG (vEEG)
      can detect various forms of abnormalities, each with its own clinical
      significance. Abnormalities can be paroxysmal (i.e., suggestive of an epileptic
      like process) or stationary. The most important unanswered question remains the
      value of detecting epileptiform activity in a nonepileptic psychiatric patient in
      predicting favorable responses to anticonvulsant treatment. Despite the many
      shortcomings of vEEG, the available evidence suggests that in the presence of
      paroxysmal activity in a nonepileptic psychiatric patient a trial of a
      psychotropic anticonvulsant may be warranted if standard treatment has failed.
      More research on the contribution of paroxysmal EEG abnormalities to the problem
      of episodic psychiatric symptoms (e.g., panic attacks, dissociative episodes,
      repeated violence) is sorely needed. It is postulated that at least some of these
      conditions may represent an epilepsy spectrum disorder. Similarly, the
      significance of the presence of a slow-wave activity (whether focal or
      generalized) also deserves further well-designed research to ascertain the exact
      clinical significance. Nonetheless, the available data suggest that further
      medical workup is necessary to ascertain the nature and degree of the pathology
      when present.

PMID- 28766470
TI  - Effects of isovalerate supplements on morphology and functional gene expression
      of rumen mucosa in pre- and post-weaning dairy calves.
AB  - Isovalerate supplements could stimulate rumen development by improving morphology
      and function of rumen mucosa, and then promote the growth of calves. This study
      was done to evaluate the effects of isovalerate supplements on morphology and
      functional gene expression of rumen mucosa in dairy calves. In total, 48 Chinese
      Holstein male calves with 15 days of age and 45.1+/-0.36 kg of BW were randomly
      assigned to four groups. The treatments were: control, low-isovalerate, moderate
      isovalerate and high-isovalerate with 0, 3, 6 and 9 g isovalerate per calf per
      day, respectively. Supplementary isovalerate was hand-mixed into milk in pre
      weaning calves and into concentrate portion in post-weaning calves. The study
      consisted of a 15-day-adaptation period and a 60-day-sampling period. Calves were
      weaned at 60 days of age. Three calves were slaughtered from each of the four
      treatments at 30, 60 and 90 days of age. The weight of body and stomach were
      measured, samples of ruminal tissues and blood were analyzed. Total stomach
      weight, total stomach to BW ratio, rumen wall and keratinized layer thickness,
      serum growth hormone and IGF-1 for both pre- and post-weaning calves increased
      linearly with increasing isovalerate supplements. Rumen to total stomach weight
      ratio, the length and width of rumen papillae, and serum beta-hydroxybutyrate
      increased linearly for post-weaning calves. However, abomasum weight to total
      stomach weight ratio decreased linearly for both pre- and post-weaning calves.
      The relative messenger RNA expression for growth hormone receptor, IGF-1 receptor
      and 3-hydroxy-3-methylglutaryl-CoA synthase 1 in rumen mucosa increased linearly
      for post-weaning calves. Our results suggested that isovalerate supplements
      promoted rumen development in a dose-dependent manner. The optimum dose was 6.0 g
      isovalerate per calf per day.

PMID- 28766471
TI  - Why is terrorism a man's business?
AB  - Terrorism, whether it is group-related or performed as lone actor terrorism, is a
      predominantly male phenomenon. Generally and throughout history, young males have
      been the main protagonists of criminal and political violence.This article aims
      to contribute, from different perspecives, to the question of what makes young
      men violent. These include neurobiological aspects, such as sex differences in
      the brain that predispose males to physical aggression and violence; gender role
      aspects, with regard to aggression and violence being basic components for
      demonstrating and reconstructing masculinity; demographic aspects of male youth
      bulges as potential breeding grounds for terrorism; aspects of group dynamics and
      identity fusion in the process of radicalization; and psychosocial
      characteristics of lone actor terrorists, which differ from group-related
      terrorists.It is concluded that in addition to ideological, political, economic,
      regional, demographic, or psychosocial causes, experiences of threatened
      masculinity may be an underlying factor and driving force for terrorism.

PMID- 28766472
TI  - Stereological analysis of gonads from diploid and triploid fish yellowtail tetra
      Astyanax altiparanae (Garutti & Britski) in laboratory conditions.
AB  - This study aimed to examine the gonadal morphology of diploid and triploid fish
      through stereological analysis. Triploid individuals were obtained after
      temperature shock (40 degrees C for 2 min) at 2 min post-fertilization and reared
      until 175 days post-fertilization (dpf). Intact eggs were used to obtain the
      diploids. Gonads were collected for histological analysis at 83, 114, 144 and 175
      dpf. Diploid females and males presented normal oogenesis and spermatogenesis
      through all the experimental period. Conversely, stereological analysis revealed
      that triploid females were sterile and oogonia were the prevalent cell type in
      the ovaries. Triploid males presented increased amounts of spermatocyte cysts and
      a large area of lumen when compared with diploids and in addition the amount of
      spermatozoa was lower than that observed for diploids. However, some triploid
      males presented spermatogenesis similar to diploids. Therefore, we concluded that
      triploidization is an interesting alternative to produce sterile individuals in
      A. altiparanae.

PMID- 28766473
TI  - Freshwater mussels (Anodonta anatina) reduce transmission of a common fish
      trematode (eye fluke, Diplostomum pseudospathaceum).
AB  - Recent results suggest that bivalves can play an important role in restraining
      the spread of various aquatic infections. However, the ability of mussels to
      remove free-living stages of macroparasites and reduce their transmission is
      still understudied, especially for freshwater ecosystems. We investigated the
      influence of the common freshwater mussel (Anodonta anatina) on the transmission
      of a trematode (eye fluke, Diplostomum pseudospathaceum), which frequently
      infects fish in farms and natural habitats. In our experiments, mussels caused a
      significant decrease (P < 0.001) in the abundance of trematode free-living
      stages, from 6520 to 1770 cercariae L-1 on average (about 4-fold in 2 h).
      Individual clearance rates of mussels were 0.6-3.7 L per hour (mean 1.9). These
      tests were followed by experimental infections of rainbow trout (Oncorhynchus
      mykiss) with different doses of D. pseudospathaceum cercariae in the presence or
      absence of mussels. Exposure of fish to cercariae in the presence of mussels
      significantly (P < 0.05) reduced the infection intensities in fish (by 30-40%) at
      all exposure doses. Our results indicate that freshwater bivalves can markedly
      reduce local cercariae densities and could be useful in mitigation of
      trematodoses harmful to fish farming.

PMID- 28766474
TI  - A systematic review of interventions to prevent suicidal behaviors and reduce
      suicidal ideation in older people.
AB  - BACKGROUND: Older people have a high risk of suicide but research in this area
      has been largely neglected. Unlike for younger age groups, it remains unclear
      what strategies for prevention exist for older adults. This systematic review
      assesses the effectiveness of interventions to prevent suicidal behavior and
      reduce suicidal ideation in this age group. METHODS: MEDLINE, EMBASE, PsycINFO,
      Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were
      searched for relevant publications from their dates of inception until 1 April
      2016. Studies included in this review report effectiveness data about
      interventions delivered to older adults to prevent suicidal behavior (suicide,
      attempted suicide, and self-harm without suicidal intent) or reduce suicidal
      ideation. A narrative synthesis approach was used to analyze data and present
      findings. RESULTS: Twenty one studies met the criteria for inclusion in the
      study. Most programs addressed risk predictors, specifically depression.
      Effective interventions were multifaceted primary care-based depression screening
      and management programs; treatment interventions (pharmacotherapy and
      psychotherapy); telephone counseling for vulnerable older adults; and community
      based programs incorporating education, gatekeeper training, depression
      screening, group activities, and referral for treatment. Most of the studies were
      of low quality apart from the primary care-based randomized controlled trials.
      CONCLUSIONS: Multifaceted interventions directed at primary care physicians and
      populations, and at-risk elderly individuals in the community may be effective at
      preventing suicidal behavior and reducing suicidal ideation in older adults.
      However, more high quality trials are needed to demonstrate successful
      interventions.

PMID- 28766475
TI  - Vulnerability of Older Adults in Disasters: Emergency Department Utilization by
      Geriatric Patients After Hurricane Sandy.
AB  - OBJECTIVE: Older adults are a potentially medically vulnerable population with
      increased mortality rates during and after disasters. To evaluate the impact of a
      natural disaster on this population, we performed a temporal and geospatial
      analysis of emergency department (ED) use by adults aged 65 years and older in
      New York City (NYC) following Hurricane Sandy's landfall. METHODS: We used an all
      payer claims database to analyze demographics, insurance status, geographic
      distribution, and health conditions for post-disaster ED visits among older
      adults. We compared ED patterns of use in the weeks before and after Hurricane
      Sandy throughout NYC and the most afflicted evacuation zones. RESULTS: We found
      significant increases in ED utilization by older adults (and disproportionately
      higher in those aged >=85 years) in the 3 weeks after Hurricane Sandy, especially
      in NYC evacuation zone one. Primary diagnoses with notable increases included
      dialysis, electrolyte disorders, and prescription refills. Secondary diagnoses
      highlighted homelessness and care access issues. CONCLUSIONS: Older adults
      display heightened risk for worse health outcomes with increased ED visits after
      a disaster. Our findings suggest the need for dedicated resources and planning
      for older adults following a natural disaster by ensuring access to medical
      facilities, prescriptions, dialysis, and safe housing and by optimizing health
      care delivery needs to reduce the burden of chronic disease. (Disaster Med Public
      Health Preparedness. 2018;12:184-193).

PMID- 28766476
TI  - General Steps to Standardize the Laboratory Measurement of Serum Total 25
      Hydroxyvitamin D.
AB  - The Vitamin D Standardization Program (VDSP) has collaborated with numerous
      groups and agencies to assemble a set of tools, i.e., a reference measurement
      system, that can be used to establish the traceability of 25-hydroxyvitamin D
      [25(OH)D] assays to relevant reference measurement procedures and reference
      materials. This is done with the goal of verifying end-user laboratory
      performance using precise statistical criteria to determine whether a specific
      assay is standardized. The purpose of this paper was to outline a set of steps
      that routine clinical and research laboratories can use to standardize their
      25(OH)D assays using these tools. These steps apply to laboratories using
      commercially developed immunoassay measurement systems as well as in-house
      assays, usually based on high HPLC or LC tandem MS measurement systems. The steps
      are (1) initial calibration, (2) initial assessment of accuracy and bias, (3)
      assessment of total percent CV and mean bias, (4) use of trueness controls, and
      (5) participation in accuracy-based performance testing and/or external quality
      assessment schemes. The goal of each laboratory assay is to have a total CV of
      <=10% and mean bias of <=5%. Rigorous and less rigorous but low-cost options for
      meeting these statistical criteria are provided. Research laboratories who
      infrequently measure 25(OH)D are advised to repeat steps 1-4 for every
      measurement cycle. For users of commercial immunoassays who have relatively
      little control over standardization, we present an option for using trueness
      controls to develop a master equation that can be used to standardize results to
      the reference methods.

PMID- 28766477
TI  - Simultaneous Spectrophotometric Determination of Elbasvir and Grazoprevir in a
      Pharmaceutical Preparation.
AB  - Three UV spectrophotometric methods have been developed for the simultaneous
      determination of two new Food and Drug Administration-approved drugs, elbasvir
      (EBV) and grazoprevir (GRV), in their combined pharmaceutical dosage form. These
      methods include dual wavelength (DW), classic least-squares (CLS), and principal
      component regression (PCR). To achieve the DW method, two wavelengths were chosen
      for each drug in a way to ensure the difference in absorbance was zero from one
      drug to the other. GRV revealed equal absorbance at 351 and 315 nm, for which the
      distinctions in absorbance were measured for the determination of EBV. In the
      same way, distinctions in absorbance at 375 and 334.5 nm were measured for the
      determination of GRV. Alternatively, the CLS and PCR models were applied to the
      spectra analysis because the synchronous inclusion of many unreal wavelengths
      rather than using a single wavelength greatly increased the precision and
      predictive ability of the methods. The proposed methods were successfully applied
      to the assay of these drugs in their pharmaceutical formulation. The obtained
      results were statistically compared with manufacturing methods. The results
      conclude that there was no significant difference between the proposed methods
      and the manufacturing method with respect to accuracy and precision.

PMID- 28766478
TI  - Novel Approach for the Simultaneous Determination of Carbinoxamine Maleate,
      Pholcodine, and Ephedrine Hydrochloride Without Interference from Coloring Matter
      in an Antitussive Preparation Using Smart Spectrophotometric Methods.
AB  - The presence of coloring matters in syrups usually interferes with the
      spectrophotometric determination of active pharmaceutical ingredients. A novel
      approach was introduced to eliminate the interference of sunset yellow (coloring
      matter) in Cyrinol syrup. Smart, simple, accurate, and selective
      spectrophotometric methods were developed and validated for the simultaneous
      determination of a ternary mixture of carbinoxamine maleate, pholcodine, and
      ephedrine hydrochloride in syrup. Four of the applied methods used ratio spectra:
      successive derivative subtraction coupled with constant multiplication,
      successive derivative of ratio spectra, ratio subtraction coupled with ratio
      difference, and ratio spectra continuous wavelet transforms zero-crossing. In
      addition, a method that was based on the presence of an isosbestic point, the
      amplitude summation method, was also established. A major advantage of the
      proposed methods is the simultaneous determination of the mentioned drugs without
      prior separation steps. These methods were successfully applied for the
      determination of laboratory-prepared mixtures and a commercial pharmaceutical
      preparation without interference from additives, thus proving the selectivity of
      the methods. No significant difference regarding both accuracy and precision was
      observed upon statistical comparison of the results obtained by the proposed
      methods with each other and with those of official or reported ones.

PMID- 28766479
TI  - An HPLC Method for the Determination of Isoflavones and the Evaluation of Their
      Antioxidant Capacity in Both Homogeneous and Microheterogeneous Systems.
AB  - In this work, we developed an HPLC method to simultaneously quantify and hence
      evaluate the stability, distribution, and antioxidant capacity of six
      isoflavones: genistein, genistin, daidzein, daidzin, glycitin, and biochanin A.
      Isoflavones have been described as having an important estrogenic activity to
      treat menopausal symptoms and can reduce postmenopausal bone loss and also
      participate in the prevention of cardiovascular diseases. These beneficial
      properties are believed derived from their capacity to act as free-radical
      scavengers. Isoflavones are formulated in capsules and creams and also can be
      used as antioxidants in liposomes. HPLC separation was achieved on an Agilent
      Hypersil ODS C18 column. The mobile phase consisted of 0.02-0.2% orthophosphoric
      acid in water-acetonitrile with gradient elution. The diode array detector was
      operated at 260 nm. The hydrophobicity of isoflavones was determined through
      their distribution in octanol-buffer. These results allowed us to establish a
      relation between chemical structure, pKa, lipophilicity, and the characteristics
      of the dispersion medium. Photolysis of hydrogen peroxide was used to measure the
      HO* scavenging capability of isoflavones. In liposomes, the order of reactivity
      of the studied compounds was genistein > biochanin A > genistin > daidzein >
      daidzin > glycitin.

PMID- 28766480
TI  - Development and Validation of an HPLC-UV Method to Quantify Tavaborole During in
      Vitro Transungual Permeation Studies.
AB  - A selective and rapid reversed-phase HPLC-UV method was developed and validated
      to quantify tavaborole (TAV; AN2690) in biological samples, i.e., in receiving
      phase and in bovine hoof membrane extract derived from in vitro transungual
      permeation studies. A simple solid-liquid extraction procedure was used to
      recover the drug from the bovine hoof slices. TAV chromatographic separation was
      achieved on a Luna PFP column (150 * 4.6 mm, 5 MUm) using a mobile phase
      consisting of a 70% phosphoric acid solution (10 mM, pH 2.0) with 30%
      acetonitrile. The detection wavelength was set to 220 nm using a UV detector. The
      method exhibited good linearity in the calibration ranges, which were 0.5-8.0 and
      0.03-2.5 MUg/mL for the receiving phase and hoof membranes, respectively. The
      obtained LOD and LOQ values were 0.023 and 0.069 MUg/mL, respectively, for the
      receiving phase and 0.0024 and 0.007 MUg/mL for the bovine hoof membrane
      extracts. In all cases, the CV for intraday and interday precision was widely
      below the limit of 2%, demonstrating good precision. The analytical method
      described was sensitive, precise, linear, and accurate and could be applicable
      for clinical and bioanalytical studies as an alternative to other analytical
      methods, which are quite expensive and not always available in research
      laboratories.

PMID- 28766481
TI  - Evaluation of a Commercial Sandwich Enzyme-Linked Immunosorbent Assay for the
      Quantification of Beta-Casomorphin 7 in Yogurt Using Solid-Phase Extraction
      Coupled to Liquid Chromatography-Tandem Mass Spectrometry as the "Gold Standard"
      Method.
AB  - This study investigated beta-casomorphin 7 (BCM7) in yogurt by means of LC-tandem
      MS (MS/MS) and enzyme-linked immunosorbent assay (ELISA) and use LC-MS/MS as the
      "gold standard" method to evaluate the applicability of a commercial ELISA. The
      level of BCM7 in milk obtained from ELISA analysis was much lower than that
      obtained by LC-MS/MS analysis and trended to increase during fermentation and
      storage of yogurt. Meanwhile, the results obtained from LC-MS/MS showed that BCM7
      degraded during stages of yogurt processing, and its degradation may have been
      caused by X-prolyl dipeptidyl aminopeptidase activity. As a result, the
      commercial sandwich ELISA kit was not suitable for the quantification of BCM7 in
      fermented dairy milk.

PMID- 28766482
TI  - Self-Reported Adherence to Capecitabine on XELOX Treatment as Adjuvant Therapy
      for Colorectal Cancer.
AB  - Adherence has become an important issue in modern oncology treatment. Most
      studies have included heterogeneous target tumor types, regimens, and therapy
      settings. Our study focused on capecitabine during capecitabine plus oxaliplatin
      (XELOX) treatment as an adjuvant therapy for colorectal cancer. The main aims of
      this study were to evaluate real-life adherence to capecitabine and to
      investigate candidate factors that might decrease adherence. We studied 338
      consecutive patients who received XELOX treatment between December 1, 2011, and
      April 30, 2015, at the Cancer Institute Hospital of the Japanese Foundation for
      Cancer Research. Our study assessed adherence to capecitabine through patient
      reported treatment diaries and interviewed nonadherents to determine the reasons
      for not taking capecitabine at a pharmaceutical outpatient clinic. We calculated
      the adherence rate in a cycle as: number of times the patient took
      capecitabine/28. Relative dose intensities and factors associated with
      deteriorating adherence to capecitabine were retrospectively surveyed from
      electronic patient records. Uni- and multivariate logistic regression analyses
      were used to investigate factors associated with optimal adherence. The study
      covered 282 patients who received 2,055 cycles of XELOX. Median adherence rate
      was 94.0% in the first cycle, and median relative dose intensity of capecitabine
      was 77.8%. The most common reasons for nonadherence were nausea/vomiting and
      diarrhea. The presence of the following factors was not significantly associated
      with adherence: ECOG performance status >=1 (p = 0.715), clinical stage (p =
      0.408), primary tumor site (p = 0.576), age >=70 years at study entry (p =
      0.757), female gender (p = 0.504), and not living alone (p = 0.579). The
      adherence rate from this study was significantly higher than the adherence from
      metastatic settings. Adherence-enhancing interventions for capecitabine in XELOX
      treatment as adjuvant therapy comprised management of nausea/vomiting and
      diarrhea.

PMID- 28766483
TI  - Transesterification of Waste Activated Sludge for Biosolids Reduction and
      Biodiesel Production.
AB  - Transesterification of waste activated sludge (WAS) was evaluated as a cost
      effective technique to reduce excess biosolids and recover biodiesel feedstock
      from activated sludge treatment processes. A laboratory-scale sequencing batch
      reactor (SBR) was operated with recycling transesterification-treated WAS back to
      the aeration basin. Seventy percent recycling of WAS resulted in a 48% reduction
      of excess biosolids in comparison with a conventional SBR, which was operated in
      parallel as the control SBR. Biodiesel recovery of 8.0% (dried weight basis) was
      achieved at an optimum transesterification condition using acidic methanol and
      xylene as cosolvent. Average effluent soluble chemical oxygen demand (COD) and
      total suspended solids (TSS) concentrations from the test SBR and control SBR
      were comparable, indicating that the recycling of transesterification-treated WAS
      did not have detrimental effect on the effluent quality. This study demonstrated
      that transesterification and recycling of WAS may be a feasible technique for
      reducing excess biosolids, while producing valuable biodiesel feedstock from the
      activated sludge process.

PMID- 28766484
TI  - Anaerobic Digestion Effluents (ADEs) Treatment Coupling with Chlorella sp.
      Microalgae Production.
AB  - Nutrient removal effectiveness from anaerobic digestion effluents (ADEs) by
      Chlorella sp. cultivation and microalgae biomass productivity were evaluated in
      this study. The results showed that the highest Chlorella sp. biomass
      productivities of 386.5 +/- 24.1 mg dry weight/L*d and 338.3 +/- 11.0 mg dry
      weight/L*d were respectively obtained with the anaerobically digested effluent of
      municipal wastewater sludge and effluent from a fermentation tank treating dairy
      wastewater. Lower (p < 0.05) microalgal growth was achieved with anaerobically
      digested effluents of maize silage and swine slurry and cattle manure. The
      increase of the initial ammonia nitrogen concentration in ADEs to the level of
      160 mg/L did not encourage Chlorella sp. productivity because of phosphorus
      limitation. The removal efficiencies of ammonia nitrogen, total nitrogen, total
      phosphorus, and chemical oxygen demand (COD) reached 99.7%, 98.6%, 88.2%, and
      58.7%, respectively, depending on the source of ADE, but not on the initial
      ammonia nitrogen concentrations.

PMID- 28766485
TI  - A Statistical Review of Alternative Zinc and Copper Extraction from Mineral
      Fertilizers and Industrial By-Products.
AB  - Rapid, accurate, and low-cost alternative analytical methods for micronutrient
      quantification in fertilizers are fundamental in QC. The purpose of this study
      was to evaluate whether zinc (Zn) and copper (Cu) content in mineral fertilizers
      and industrial by-products determined by the alternative methods USEPA 3051a, 10%
      HCl, and 10% H2SO4 are statistically equivalent to the standard method,
      consisting of hot-plate digestion using concentrated HCl. The commercially
      marketed Zn and Cu sources in Brazil consisted of oxides, carbonate, and sulfate
      fertilizers and by-products consisting of galvanizing ash, galvanizing sludge,
      brass ash, and brass or scrap slag. The contents of sources ranged from 15 to 82%
      and 10 to 45%, respectively, for Zn and Cu. The Zn and Cu contents refer to the
      variation of the elements found in the different sources evaluated with the
      concentrated HCl method as shown in Table 1. A protocol based on the following
      criteria was used for the statistical analysis assessment of the methods: F-test
      modified by Graybill, t-test for the mean error, and linear correlation
      coefficient analysis. In terms of equivalents, 10% HCl extraction was equivalent
      to the standard method for Zn, and the results of the USEPA 3051a and 10% HCl
      methods indicated that these methods were equivalents for Cu. Therefore, these
      methods can be considered viable alternatives to the standard method of
      determination for Cu and Zn in mineral fertilizers and industrial by-products in
      future research for their complete validation.

PMID- 28766487
TI  - Survival and Antibiotic Resistance of Bacteria in Artificial Snow Produced from
      Contaminated Water.
AB  - This study shows microbiological contamination of water in two main Podhale
      rivers, whose resources are used for the production of artificial snow, and the
      resulting snow contamination. Thirty-one E. coli strains were isolated from snow
      at two ski stations in the studied region, their antimicrobial resistance was
      determined, and the presence of extended spectrum beta-lactamase (ESBL) genes was
      searched for. The results indicate that the waters of both rivers are severely
      contaminated, resulting in the contamination of artificial snow with, among
      others, thermotolerant E. coli. E. coli isolated from snow were most frequently
      resistant to ampicillin (74.19%) and amoxicillin/clavulanate (51.61% isolates).
      Aminoglycosides and third generation cephalosporins were most efficient among the
      tested antimicrobials. Some bacterial strains were multidrug resistant and three
      strains exhibited the ESBL mechanism. Molecular analyses showed the presence of
      ESBL genes in the same three strains. Genetic variation among E. coli indicates
      that only some genotypes are able to survive the artificial snow production
      process.

PMID- 28766486
TI  - Treating persistent asthma in rural Rwanda: characteristics, management and 24
      month outcomes.
AB  - SETTING: In 2007, the Rwandan Ministry of Health, with support from Partners In
      Health, introduced a district-level non-communicable disease programme that
      included asthma care. OBJECTIVE: To describe the demographics, management and 24
      month outcomes of asthma patients treated at three rural district hospitals in
      Rwanda. DESIGN: We retrospectively reviewed electronic medical records of asthma
      patients enrolled from January 2007 to December 2012, and extracted information
      on demographics, clinical variables and 24-month outcomes. RESULTS: Of the 354
      patients, 66.7% were female and 41.5% were aged between 41 and 60 years. Most
      patients (53.1%) were enrolled with moderate persistent asthma, 40.1% had mild
      persistent asthma and 6.8% had severe persistent asthma. Nearly all patients
      (95.7%) received some type of medication, most commonly a bronchodilator. After
      24 months, 272 (76.8%) patients were still alive and in care, 21.1% were lost to
      follow-up, 1.7% had died and 0.3% had transferred out. Of the 121 patients with
      an updated asthma classification at 24 months, the severity of their asthma had
      decreased: 17.4% had moderate and 0.8% had severe persistent asthma. CONCLUSION:
      Our findings show improvements in asthma severity after 24 months and reasonable
      rates of loss to follow-up, demonstrating that asthma can be managed effectively
      in rural, resource-limited settings.

PMID- 28766488
TI  - Effect of High Strength Food Wastes on Anaerobic Codigestion of Sewage Sludge.
AB  - Anaerobic codigestion has been practiced at water resource recovery facilities
      to increase methane production, but the impact of many variables is still not
      well understood. In this study, the feasibility of codigesting fats, oils, and
      grease (FOG), and other high strength wastes (HSWs) with municipal sewage sludge
      was investigated. Four laboratory-scale digesters were operated at a working
      volume of 9.75 L, 15 days solids retention time (SRT), and at a temperature of 37
      degrees C. Wastes including whey (cheese), juice, grease trap waste (GTW), and
      dissolved air flotation waste (DAF), along with municipal sewage sludge, were fed
      to the digesters in varying amounts. The addition of HSWs led to higher methane
      production at lower organic loadings. However, at higher organic loadings, the
      GTW appeared to be toxic to methanogens, leading to a decrease in digester pH and
      biogas production, and an accumulation of volatile fatty acids within the
      digester.

PMID- 28766489
TI  - Using Safranin T as a Charge Transfer-Sensitive Ion-Pairing Reagent in Ultrasound
      Assisted Cloud Point Extraction: Determination of Bisphenol A in Selected
      Beverages.
AB  - In this study, a new ultrasonic-assisted cloud point extraction method coupled
      with spectrophotometry was developed to extract from and determine bisphenol A
      (BPA) in a sample matrix. The method is based on charge transfer-sensitive ion
      pairing complex formation between BPA and Safranin T in the presence of nitrate
      in a micellar interface at pH 5.0. The variables affecting extraction efficiency
      were optimized. A good linear relationship with a significant sensitivity
      difference was obtained in the ranges of 2-40 and 2-120 ug/L with LODs of 0.54
      and 0.38 ug/L after preconcentration with two different extractants,
      respectively. From a preconcentration of a 15 mL sample, a preconcentration
      factor of 60 was obtained. Due to the lack of a certified material compatible
      with the sample matrix, the method was validated by conducting intraday and
      interday accuracy and precision studies based on two spiked QC samples (with a
      recovery rate greater than 94% and an RSD ranging from 3.8 to 5.9%). Moreover,
      the beverage samples were analyzed by the standard addition method to control for
      possible matrix effects. BPA was detected in the range of 1.8-7.2 ug/L in
      beverages with Triton X-114, whereas the levels changed to a range of 1.8-7.3
      ug/L with Triton X-45. In such a way not to create a threat, these levels were
      considerably lower than the specific migration limit set by the European Union.

PMID- 28766490
TI  - Validated Analytical Methods for the Determination of Drugs Used in the Treatment
      of Hyperemesis Gravidarum in Multiple Formulations.
AB  - Quantitative multicomponent analysis is considered an analytical goal to save
      time and cost in analysis. Hence, this work aimed to provide sensitive and
      selective UV-spectrophotometric, chemometric manipulation, and ultra-performance
      LC (UPLC) methods for the determination of well-known coformulated antiemetics
      used in pregnancy, namely pyridoxine HCl (PYR), meclozine HCl, and cyclizine. The
      developed UV-spectrophotometric methods are dual wavelength in ratio spectra and
      first derivative of the ratio spectra with which PYR was determined selectively
      at 290.8 nm, whereas the other drugs in a ternary mixture were determined from
      their ratio spectra using a spectrum of PYR as a divisor in 0.1 M HCl. An
      ecofriendly partial least-squares regression chemometric method was applied to
      raw UV absorbance data for the determination of the ternary mixture in a 218-355
      nm range using a three-factor, three-level design with water as the green
      solvent. A gradient UPLC method was developed and successfully resolved the
      ternary mixture within 5 min. Different ratios of water (adjusted to pH 3 with
      phosphoric acid) and methanol were delivered at 0.5 mL/min as the mobile phase
      into a Hypersil Gold C18 column (50 * 2.1 mm, 1.9 um). The developed methods were
      successfully applied to different pharmaceutical formulations containing the
      aforementioned drugs and validated according to the International Conference on
      Harmonization guidelines. The results obtained were reproducible and reliable and
      can be applied for routine analysis and QC in laboratories.

PMID- 28766491
TI  - A case of severe nephrotoxicity associated with long-term dietary supplement use.
AB  - Dietary supplements are widely used for their perceived health benefits without
      side effects and hence have minimal regulation. However, they have been
      associated with various toxicities including kidney disease. We report a 65-year
      old male who had very heavy daily intake of dietary supplements for 3 years. He
      presented with acute kidney injury and nephrotic-range proteinuria. The renal
      biopsy showed acute tubular necrosis with vacuolization, acute interstitial
      nephritis, and secondary membranous nephropathy, consistent with an non-steroidal
      anti-inflammatory drug (NSAID)-like nephropathy. This was postulated to be
      related to the cyclooxygenase (COX) inhibitors (anthocyanins) in cherry extract
      that was a significant part of the patient's dietary supplement use. His
      proteinuria completely resolved and serum creatinine stabilized after
      discontinuation of all dietary supplements and a prolonged (5 months) course of
      prednisone. Clinicians are advised to specifically inquire about dietary
      supplements, especially cherry extract, as a potential cause of new-onset renal
      failure and proteinuria.?.

PMID- 28766492
TI  - MODY3, renal cysts, and Dandy-Walker variants with a microdeletion spanning the
      HNF1A gene.
AB  - Heterozygous hepatocyte nuclear factor-1-alpha gene (<italic>HNF1A</italic>)
      mutations are the most common cause of maturity-onset diabetes of the young
      (MODY), but they rarely involve extrahepatic manifestations. Renal cysts and
      diabetes syndrome can be caused by <italic>HNF1B</italic> mutations. No
      association between MODY3 and Dandy-Walker variants (DWV) has been reported.
      <italic>HNF1A</italic> mutations might be responsible for renal malformations. In
      a Japanese girl with glycosuria, developmental delay, mental retardation, renal
      cysts, and DWV, the <italic>HNF1B</italic> gene had no mutations. Array
      comparative genomic hybridization analysis identified a de-novo interstitial
      12q24.22-q24.31 deletion of 5.6 Mb encompassing the <italic>HNF1A</italic> gene,
      which is compatible with a diagnosis of MODY3. The variety of phenotypes suggests
      a novel microdeletion syndrome spanning the <italic>HNF1A</italic> gene. Because
      <italic>HNF1B</italic> functions as an <italic>HNF1A/HNF1B</italic> heterodimer,
      haploinsufficient <italic>HNF1A</italic> interacts with a certain
      <italic>HNF1B</italic> haplotype. The resulting truncated heterodimer might
      engender renal cysts. More patients with well-defined deletion within 12q.24.31
      must be evaluated to produce a detailed genotype-phenotype correlation and to
      elucidate this emerging microdeletion syndrome.?.

PMID- 28766493
TI  - Evaluation of the safety and immunogenicity of subcutaneous HX575 epoetin alfa in
      the treatment of anemia associated with chronic kidney disease in predialysis and
      dialysis patients?.
AB  - AIM: To assess the safety and immunogenicity of subcutaneous (SC) HX575 (epoetin
      alpha) in dialysis- and nondialysis-dependent adult patients with chronic kidney
      disease (CKD). METHODS: Open-label, single-arm, multicenter study in patients (n
      = 416) from Germany, Italy, Poland, Romania, Russia, Turkey, and Ukraine.
      RESULTS: Mean (standard deviation (SD)) age was 52.3 (15.8) years, all patients
      were Caucasian, and similar proportions were male/female. 250 patients (60.1%)
      were erythropoiesis-stimulating agent (ESA)-naive, and 166 (39.9%) were receiving
      ESA maintenance therapy at study start; mean (SD) on-study treatment duration
      with HX575 was 43.4 (15.8) weeks and 45.3 (13.7) weeks, respectively. Binding
      antierythropoietin (EPO) antibodies were detected by radioimmunoprecipitation
      (RIP) assay in 7 patients (1.7%; incidence 0.019); 5 of these were ESA-naive at
      study entry. No patient developed neutralizing antibodies as determined in a cell
      based epoetin neutralizing assay. Of the 7 patients with a positive binding anti
      EPO RIP assay, 4 tested negative at later time points while continuing HX575
      treatment. Three patients had low titers of anti-EPO antibodies at the last study
      assessment. There were no clinical signs of immunogenicity or hypersensitivity.
      CONCLUSIONS: SC HX575 was effective for correcting and maintaining correction of
      anemia, and the mean weekly dose remained stable over time.?.

PMID- 28766494
TI  - Resting energy expenditure: a valuable predictor for KT/Vurea in peritoneal
      dialysis patients?.
AB  - OBJECTIVE: The objective of this study was to identify an effective method for
      predicting small-molecule solute removal at the commencement of or before
      peritoneal dialysis (PD). METHODS: The PD patients with a dialysis delivery of 8
      L/d and a residual kidney function (RKF) <= 5 mL/min were enrolled in the study.
      Fat-free lean body mass (FFM) and resting energy expenditure (REE) were measured
      using bioelectrical impedance (BIA). A receiver operating characteristic (ROC)
      curve was drawn to determine the threshold value for REE. The patients were
      divided into two groups, group A (lower REE) and group B (higher REE), based on
      their REE value. RESULTS: In total, 164 PD patients were enrolled between April
      2013 and February 2015. REE was positively correlated with serum creatinine
      (Scr), blood urea nitrogen (BUN), blood uric acid (UA), body mass index (BMI),
      and body surface area (BSA) and negatively correlated with total
      KT/V<sub>urea</sub> (KT/V) and hemoglobin (Hb). REE (HR = 0.987, 95% CI = 0.975 -
      1.000, p = 0.044) was the only predictor for KT/V. When REE was less than 1469.2
      kal/d, it was easier to achieve the target KT/V. The patients in group B had
      significantly larger body size than those in group A; however, Hb level and total
      KT/V for group B were significantly lower than those for group A. CONCLUSION: REE
      may be a helpful indicator for choosing a suitable dialysis modality for patients
      with end-stage renal disease (ESRD) and for improving the prognosis after PD.?.

PMID- 28766495
TI  - Pulmonary embolism with endovascular thrombolysis for thrombosed hemodialysis
      arteriovenous access?.
AB  - AIMS: Acute thrombosis of hemodialysis (HD) arteriovenous access is an urgent
      problem for HD patients and is commonly managed by endovascular thrombolysis.
      Pulmonary embolism (PE) is a recognized complication of HD access thrombosis and
      thrombolysis but the risk and outcomes are unclear. This study aims to determine
      the incidence, predictors, and outcomes of PE after endovascular thrombolysis of
      HD arteriovenous access in patients presenting with acute thrombosis. MATERIALS
      AND METHODS: A single-center retrospective study was performed for all adult
      chronic kidney disease patients undergoing arteriovenous access thrombolysis
      between January 1, 2012, and December 31, 2014. Investigation for PE with CT
      pulmonary angiography or ventilation/perfusion scintigraphy (V/Q scan) was
      performed as clinically directed by the managing clinicians. In cases diagnosed
      with PE, the pulmonary embolism severity index (PESI) was calculated. RESULTS: A
      total of 48 (median age 68) patients underwent 74 thrombolysis procedures.
      Thrombolysis techniques were divided into pharmacological (44.6%), mechanical
      (17.6%), or pharmacomechanical (37.8%). Clinical success was achieved in 56/74
      (75.7%) of procedures. Five episodes of thrombolysis for access thrombosis (6.8%)
      were associated with clinically symptomatic PE. The PESI score ranged from 51 to
      127. All patients with PE were managed with 3 - 6 months of anticoagulation and
      recovered clinically. There were no statistically significant differences in
      baseline characteristics, methods of thrombolysis, or clot burden in patients
      that developed a PE. CONCLUSION: There is a clinically significant risk of
      symptomatic PE after arteriovenous access thrombolysis for access thrombosis in
      HD patients.?.

PMID- 28766496
TI  - Mixed hemangioblastoma and ependymoma collision tumor of the cerebellum.

PMID- 28766497
TI  - Predictive factors for the effect of acid-reducing agents on drug exposure.
AB  - OBJECTIVES: Acid-reducing agents (ARAs) may affect drug exposure for orally
      administered drugs exhibiting pH-dependent solubility. The aim of this research
      was to investigate factors predicting the effect of ARAs on drug exposure. Dose
      (mg)/250 mL/solubility at neutral pH and ratio of solubility at acidic pH to that
      at neutral pH were investigated as potential factors. MATERIALS AND METHODS: Drug
      drug interaction (DDI) study results with ARAs were selected based on PubMed
      search from 2007 to 2016 and novel drug approvals at the US Food and Drug
      Administration (FDA) from 2014 to 2016. For the selected drugs, solubility data
      at acidic and neutral pH were obtained from publications, FDA and European
      Medicines Agency (EMA) review report, and Japanese interview form. RESULTS: 32
      DDI study results with ARAs from 27 drugs having solubility data were obtained.
      The effect of ARAs on the C<sub>max</sub> or AUC ratio% (with/without ARAs)
      decreased with the increasing values of both factors, but the ratio of solubility
      showed higher values of squared correlation coefficient R2 (0.75 - 0.78) than the
      dose (mg)/250 mL/solubility at neutral pH (0.48 - 0.59). CONCLUSION: Ratio of
      solubility at acidic pH to that at neutral pH was a good predictor to estimate
      the effect of ARAs on drug exposure. Prediction of the effect of ARAs on drug
      exposure using solubility data would help to consider the necessity and timing
      for conducting a dedicated DDI study with ARAs and contribute to efficient drug
      development.?.

PMID- 28766498
TI  - Comparison of first- and second-generation antihistamine prescribing in elderly
      outpatients: A health insurance database study in 2013.
AB  - BACKGROUND: This descriptive study analyzed the scale of first- and second
      generation antihistamine prescription in elderly outpatients in Korea and the
      characteristics associated with this prescription. MATERIALS AND METHODS: We
      conducted a drug utilization study using the Korea Health Insurance Review and
      Assessment Service-Aged Patient Sample (HIRA-APS) database from January 1 to
      December 31, 2013. The study subjects were elderly outpatients aged 65 years and
      older who were prescribed antihistamines. The study drugs included 6 first
      generation and 16 second-generation antihistamines. The prescription pattern of
      first-generation antihistamines was based on region, diagnosis, and clinical
      specialty. Multivariate logistic regression analysis was used to determine the
      factors associated with first-generation antihistamine prescription. Odds ratios
      (ORs) with 95% confidence interval (CI) were calculated. RESULTS: A total of
      1,152,556 elderly outpatients were identified as having visited various medical
      facilities in 2013, of which 23.4% received at least one prescription for first
      generation antihistamine monotherapy. First-generation antihistamines were more
      likely to be prescribed in secondary care hospitals (OR = 1.74; 95% CI 1.69 -
      1.78) than in tertiary care hospitals, and in urban areas (OR = 1.21; 95% CI 1.20
      - 1.21) than in the Seoul metropolitan area. First-generation antihistamines were
      also more likely to be prescribed for treating the common cold (OR = 1.06; 95% CI
      1.05 - 1.06) than any other disease. CONCLUSION: A large proportion (23.4%) of
      elderly outpatients in Korea received prescriptions for first-generation
      antihistamines. Efforts to reduce prescriptions of first-generation
      antihistamines are recommended, especially prescriptions associated with common
      cold diagnosis in secondary care hospitals and in urban areas.?.

PMID- 28766499
TI  - Association between platelet function and recurrent ischemic vascular events
      after TIA and minor stroke?.
AB  - Platelet activation and aggregation play an important role in the pathological
      and physiological processes of recurrent ischemic vascular events in stroke
      patients. The purpose of this study is to determine the association between
      platelet function measured in the acute period and recurrent ischemic vascular
      events in patients with transient ischemic attack (TIA) or minor stroke. A total
      of 417 patients who were within the 24-hour period of clopidogrel-aspirin therapy
      after onset of a minor stroke or high-risk transient ischemic attack according to
      the Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular
      Events (CHANCE) trial were included in this study. The platelet aggregation ratio
      was detected using a method of continuous platelet counting; patients underwent
      CYP2C19 genotyping, and the baseline data were recorded. The patients underwent a
      6-month follow-up period during which the recurrent ischemic vascular events were
      observed. Logistic regression analysis was performed to obtain the risk factors
      for recurrent ischemic vascular events. The number of patients with recurrent
      ischemic events who had an arachidonic acid-induced maximum platelet aggregation
      ratio (MAR-AA) (aspirin 100 mg) (31.85 +/- 12.86 vs. 26.71 +/- 12.44, p = 0.007)
      and adenosine diphosphate-induced maximum platelet aggregation ratio (MAR-ADP)
      after the administration of 75 mg clopidogrel for 12 +/- 2 days (65.82 +/- 10.72
      vs. 53.10 +/- 12.98, p < 0.001) was significantly higher compared with the no
      ischemic vascular event group. Multivariate logistic regression analyses showed
      that being a carrier of the CYP2C19 loss-of-function (LOF) allele (OR = 2.308,
      95% CI: 1.087 ~ 4.901, p = 0.029) as well as the MAR-AA (aspirin 100 mg) (OR =
      1.028, 95% CI: 1.006  ~  1.052, p = 0.014) and MAR-ADP after the administration
      of 75 mg clopidogrel (OR = 1.067, 95% CI: 1.037 ~ 1.095, p < 0.001) were risk
      factors for ischemic vascular events. The MAR-ADP after the administration of 75
      mg clopidogrel was significantly higher in patients who were carriers of the
      CYP2C19 (LOF) allele compared with non-carriers (57.53 +/- 13.32 vs. 50.86 +/-
      12.55, p < 0.001), and no significant differences between the CYP2C19 LOF allele
      carriers and non-carriers in the MAR-ADP were detected after the administration
      of 300 mg clopidogrel (37.18 +/- 11.36 vs. 35.86 +/- 12.49, p = 0.264). Being a
      carrier of the CYP2C19 LOF allele has a significant influence on clopidogrel
      response. Platelet function is closely related to recurrent ischemic vascular
      events in acute minor stroke or TIA patients.?.

PMID- 28766500
TI  - A bioequivalence study of two memantine formulations in healthy Chinese male
      volunteers?.
AB  - OBJECTIVE: The aim of the current study is to evaluate the bioequivalence between
      the test and reference formulations of memantine in a single-dose, two-period and
      two-sequence crossover study with a 44-day washout interval. MATERIALS AND
      METHODS: A total of 20 healthy Chinese male volunteers were enrolled and
      completed the study, after oral administration of single doses of 10 mg test and
      reference formulations of memantine. The blood samples were collected at
      different time points and memantine concentrations were determined by a fully
      validated HPLC-MS/MS method. The evaluated pharmacokinetic parameters (test vs.
      reference) including C<sub>max</sub> (18 +/- 3.2 vs. 17.8 +/- 3.4), AUC<sub>0
      t</sub> (1,188.5 +/- 222.2 vs. 1,170.9 +/- 135.7), and AUC<sub>0-infinity</sub>
      (1,353.3 +/- 258.6 vs. 1,291.3 +/- 136.7) values were assessed for bioequivalence
      based on current guidelines. RESULTS: The observed pharmacokinetic parameters of
      memantine test drug were similar to those of the reference formulation. The 90%
      confidence intervals of test/reference ratios for C<sub>max</sub>, AUC<sub>0
      t</sub>, and AUC<sub>0-infinity</sub> were within the bioequivalence acceptance
      range of 80 - 125%. CONCLUSION: The results obtained from the healthy Chinese
      subjects in this study suggests that the test formulation of memantine 10 mg
      tablet is bioequivalent to the reference formulation (Ebixa<sup>(r)</sup>10 mg
      tablet).?.

PMID- 28766501
TI  - Sarcocystis spp. in domestic sheep in Kunming City, China: prevalence,
      morphology, and molecular characteristics.
AB  - Sheep (Ovis aries) are intermediate hosts for at least six named species of
      Sarcocystis: S. tenella, S. arieticanis, S. gigantea, S. medusiformis, S.
      mihoensis, and S. microps. Here, only two species, S. tenella and S. arieticanis,
      were found in 79 of 86 sheep (91.9%) in Kunming, China, based on their
      morphological characteristics. Four genetic markers, i.e., 18S rRNA gene, 28S
      rRNA gene, mitochondrial cox1 gene, and ITS-1 region, were sequenced and
      characterized for the two species of Sarcocystis. Sequences of the three former
      markers for S. tenella shared high identities with those of S. capracanis in
      goats, i.e., 99.0%, 98.3%, and 93.6%, respectively; the same three marker
      sequences of S. arieticanis shared high identities with those of S. hircicanis in
      goats, i.e., 98.5%, 96.5%, and 92.5%, respectively. No sequences in GenBank were
      found to significantly resemble the ITS-1 regions of S. tenella and S.
      arieticanis. Identities of the four genetic markers for S. tenella and S.
      arieticanis were 96.3%, 95.4%, 82.5%, and 66.2%, respectively.

PMID- 28766502
TI  - Transient Neonatal Diabetes due to a Mutation in KCNJ11 in a Child with
      Klinefelter Syndrome.
AB  - Klinefelter syndrome is the most frequent chromosomal aneuploidy in males
      occurring in about 1 in 660 males. Epidemiological studies have demonstrated
      increased risk of type 1 diabetes and type 2 diabetes in adults with Klinefelter
      syndrome. There is only one previous report of neonatal diabetes in a patient
      with Klinefelter syndrome. We report transient neonatal diabetes due to a
      pathogenic heterozygous variant in KCNJ11 in a male infant with Klinefelter
      syndrome. A 78-day old male infant was noted to have sustained hyperglycemia with
      serum glucose ranging between 148 mg/dL (8.2 mmol/L) and 381 mg/dL (21.2 mmol/L)
      three days after undergoing a complete repair of an atrioventricular defect.
      Hemoglobin A1c was 6.6%. The patient was born at term with a birth weight of 2.16
      kg following a pregnancy complicated by gestational diabetes that was controlled
      with diet. The patient was initially started on a continuous intravenous insulin
      drip and subsequently placed on subcutaneous insulin (glargine, human isophane
      and regular insulin). Insulin was gradually decreased and eventually discontinued
      at seven months of age. Chromosomal microarray at 11 weeks of age showed XXY and
      a panel-based, molecular test for neonatal diabetes revealed a pathogenic
      heterozygous variant c.685G>A (p.Glu229Lys) in KCNJ11. The patient is now 34
      months old and continues to have normal fasting and post-prandial glucose and
      HbA1C levels. The patient will need prospective follow up for assessment of his
      glycemic status. To our knowledge this is the second reported case of neonatal
      diabetes in an infant with Klinefelter syndrome and the first due to a mutation
      in the KCNJ11 in a patient with Klinefelter syndrome.

PMID- 28766503
TI  - Could Alerting Physicians for Low Alkaline Phosphatase Levels Be Helpful in Early
      Diagnosis of Hypophosphatasia?
AB  - OBJECTIVE: Hypophosphatasia (HPP) is an inborn error of metabolism with
      significant morbidity and mortality. Its presentation is nonspecific leading to
      delayed or missed diagnosis. Low alkaline phosphatase (ALP) is a diagnostic test.
      Unlike high ALP, low level is commonly not flagged by laboratories as abnormal. A
      new treatment was shown to be effective in HPP. In this study we aimed to
      establish the frequency of low ALP levels requiring notification to physicians by
      the laboratory and also to describe the clinical manifestations of patients
      presenting with low ALP for a possible diagnosis of HPP. METHODS: Patients under
      age 18 years with low ALP levels were identified from biochemistry records over a
      period of 6 months. Reference ranges were used as per the Associated Regional and
      University Pathologists Reference Laboratory (Utah, USA). Electronic results for
      patients with low levels were checked for flagging as abnormal/low ALP results.
      Charts of identified patients were reviewed. Presenting features were categorized
      under groups of disorders. RESULTS: ALP levels were tested in 2890 patients. 702
      had values less than 160 U/L. Of these patients, 226 (32%) had age/gender
      specific low ALP. None of the low ALP results was flagged as low. Twenty-one had
      more than one low reading and their charts were reviewed. Four patients in the
      neuromuscular and four in the miscellaneous group presented with features
      consistent with HPP despite these patients having no specific diagnoses.
      CONCLUSION: Laboratories do not alert physicians in cases with low ALP levels. A
      persistently low level in patients with unspecified diagnoses could be a key to
      diagnose HPP. Implementing lab-specific ranges and alerting for low levels could
      prompt physicians to investigate for undiagnosed HPP.

PMID- 28766504
TI  - Serum Thyroid-Stimulating Hormone Levels and Body Mass Index Percentiles in
      Children with Primary Hypothyroidism on Levothyroxine Replacement.
AB  - OBJECTIVE: To determine the association, if any, between thyroid-stimulating
      hormone (TSH) levels and body mass index (BMI) percentiles in children with
      primary hypothyroidism who are chemically euthyroid and on treatment with
      levothyroxine. METHODS: This retrospective cross-sectional study consisted of a
      review of medical records from RUSH Medical Center and Stroger Hospital, Chicago,
      USA of children with primary hypothyroidism who were seen in the clinic from 2008
      to 2014 and who were chemically euthyroid and on treatment with levothyroxine for
      at least 6 months. The patients were divided into two groups based on their TSH
      levels (0.34-<2.5 mIU/L and >=2.5-5.6 mIU/L). The data were analyzed by Spearman
      rank correlation, linear regression, cross tabulation and chi-square, Mann
      Whitney U test, and Kruskal-Wallis test. RESULTS: One hundred and forty-six
      children were included, of which 26% were obese (BMI >=95%), 21.9% overweight
      (BMI >=85-<95%), and 52.1% of a healthy weight (BMI >=5-<85%). There was a
      significant positive correlation between TSH and BMI percentiles (r=0.274,
      p=0.001) and a significant negative correlation between TSH and serum free T4 (r=
      0.259, p=0.002). In the lower TSH group, 68.4% of the children had a healthy
      weight, while the percentage of obese children was 60.5% in the upper TSH group
      (p=0.012). CONCLUSION: In children diagnosed with primary hypothyroidism who are
      chemically euthyroid on treatment with levothyroxine, there is a positive
      association between higher TSH levels and higher BMI percentiles. However, it is
      difficult to establish if the higher TSH levels are a direct cause or a
      consequence of the obesity. Further studies are needed to establish causation
      beyond significant association.

PMID- 28766505
TI  - Are rapid changes in brain elasticity possible?
AB  - Elastography of the brain is a topic of clinical and preclinical research,
      motivated by the potential for viscoelastic measures of the brain to provide
      sensitive indicators of pathological processes, and to assist in early diagnosis.
      To date, studies of the normal brain and of those with confirmed neurological
      disorders have reported a wide range of shear stiffness and shear wave speeds,
      even within similar categories. A range of factors including the shear wave
      frequency, and the age of the individual are thought to have a possible
      influence. However, it may be that short term dynamics within the brain may have
      an influence on the measured stiffness. This hypothesis is addressed
      quantitatively using the framework of the microchannel flow model, which derives
      the tissue stiffness, complex modulus, and shear wave speed as a function of the
      vascular and fluid network in combination with the elastic matrix that comprise
      the brain. Transformation rules are applied so that any changes in the fluid
      channels or the elastic matrix can be mapped to changes in observed elastic
      properties on a macroscopic scale. The results are preliminary but demonstrate
      that measureable, time varying changes in brain stiffness are possible simply by
      accounting for vasodynamic or electrochemical changes in the state of any region
      of the brain. The value of this preliminary exploration is to identify possible
      mechanisms and order-of-magnitude changes that may be testable in vivo by
      specialized protocols.

PMID- 28766506
TI  - Studying the mechanical responses of proteins using magnetic tweezers.
AB  - The mechanical stability of proteins has been extensively studied using AFM as a
      single-molecule force spectroscopy method. While this has led to many important
      results, these studies have been mainly limited to fast unfolding at a high-force
      regime due to the rapid mechanical drift in most AFM stretching experiments.
      Therefore, there is a gap between the knowledge obtained at a high-force regime
      and the mechanical properties of proteins at a lower force regime which is often
      more physiologically relevant. Recent studies have demonstrated that this gap can
      be addressed by stretching single protein molecules using magnetic tweezers, due
      to the excellent mechanical stability this technology offers. Here we review
      magnetic tweezers technology and its current application in studies of the force
      dependent stability and interactions of proteins.

PMID- 28766507
TI  - Charge transfer in time-dependent density functional theory.
AB  - Charge transfer plays a crucial role in many processes of interest in physics,
      chemistry, and bio-chemistry. In many applications the size of the systems
      involved calls for time-dependent density functional theory (TDDFT) to be used in
      their computational modeling, due to its unprecedented balance between accuracy
      and efficiency. However, although exact in principle, in practise approximations
      must be made for the exchange-correlation functional in this theory, and the
      standard functional approximations perform poorly for excitations which have a
      long-range charge-transfer component. Intense progress has been made in
      developing more sophisticated functionals for this problem, which we review. We
      point out an essential difference between the properties of the exchange
      correlation kernel needed for an accurate description of charge-transfer between
      open-shell fragments and between closed-shell fragments. We then turn to charge
      transfer dynamics, which, in contrast to the excitation problem, is a highly non
      equilibrium, non-perturbative, process involving a transfer of one full electron
      in space. This turns out to be a much more challenging problem for TDDFT
      functionals. We describe dynamical step and peak features in the exact functional
      evolving over time, that are missing in the functionals currently used. The
      latter underestimate the amount of charge transferred and manifest a spurious
      shift in the charge transfer resonance position. We discuss some explicit
      examples.

PMID- 28766508
TI  - Better band gaps for wide-gap semiconductors from a locally corrected exchange
      correlation potential that nearly eliminates self-interaction errors.
AB  - This work constitutes a comprehensive and improved account of electronic
      structure and mechanical properties of silicon-nitride ([Formula: see text]
      [Formula: see text]) polymorphs via van Leeuwen and Baerends (LB) exchange
      corrected local density approximation (LDA) that enforces the exact exchange
      potential asymptotic behavior. The calculated lattice constant, bulk modulus, and
      electronic band structure of [Formula: see text] [Formula: see text] polymorphs
      are in good agreement with experimental results. We also show that, for a single
      electron in a hydrogen atom, spherical well, or harmonic oscillator, the LB
      corrected LDA reduces the (self-interaction) error to exact total energy to 
      ~10%, a factor of three to four lower than standard LDA, due to a dramatically
      improved representation of the exchange-potential.

PMID- 28766510
TI  - A fractal physics explanation for acute thrombotic occlusion in an apparently
      healthy coronary artery.

PMID- 28766509
TI  - High-density lipoprotein metabolism and reverse cholesterol transport: strategies
      for raising HDL cholesterol.
AB  - A key to effective treatment of cardiovascular disease is to understand the
      body's complex lipoprotein transport system. Reverse cholesterol transport (RCT)
      is the process of cholesterol movement from the extrahepatic tissues back to the
      liver. Lipoproteins containing apoA-I [highdensity lipoprotein (HDL)] are key
      mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins
      containing apoB) are involved in the lipid delivery pathway. HDL particles are
      heterogeneous; they differ in proportion of proteins and lipids, size, shape, and
      charge. HDL heterogeneity is the result of the activity of several factors that
      assemble and remodel HDL particles in plasma: ATP-binding cassette transporter A1
      (ABCA1), lecithin cholesterol acyltransferase (LCAT), cholesteryl ester transfer
      protein (CETP), hepatic lipase (HL), phospholipid transfer protein (PLTP),
      endothelial lipase (EL), and scavenger receptor class B type I (SR-BI). The RCT
      pathway consists of the following steps: 1. Cholesterol efflux from peripheral
      tissues to plasma, 2. LCAT-mediated esterification of cholesterol and remodeling
      of HDL particles, 3. direct pathway of HDL cholesterol delivery to the liver, and
      4. indirect pathway of HDL cholesterol delivery to the liver via CETP-mediated
      transfer There are several established strategies for raising HDL cholesterol in
      humans, such as lifestyle changes; use of drugs including fibrates, statins, and
      niacin; and new therapeutic approaches. The therapeutic approaches include CETP
      inhibition, peroxisome proliferator-activated receptor (PPAR) agonists, synthetic
      farnesoid X receptor agonists, and gene therapy. Results of clinical trials
      should be awaited before further clinical management of atherosclerotic
      cardiovascular disease.

PMID- 28766511
TI  - Unusual cardiac involvement in granulomatosis with polyangiitis manifesting as
      acute congestive heart failure.

PMID- 28766512
TI  - Radiofrequency ablation of accessory pathways in a toddler with Ebstein's anomaly
      and functional single ventricle physiology.

PMID- 28766513
TI  - Is electrocardiography alone enough to evaluate the right ventricular involvement
      to predict short-term outcome?

PMID- 28766514
TI  - Platelet reactivity unit (PRU) in patients undergoing elective PCI: Rethinking
      the optimal cut point.

PMID- 28766515
TI  - Impressions from EuroPCR Course 2017.

PMID- 28766516
TI  - Complete heart block presenting with de Musset's sign.

PMID- 28766517
TI  - The difficulties of being a physician.

PMID- 28766518
TI  - Saah electrocardiography: An insight toward microwaveform of atrioventricular
      node and His bundle potentials.

PMID- 28766519
TI  - [The possibilities for diagnostics of prescription of death coming based on the
      changes in the lumbar intervertebral disks (the comparison of the morphological,
      immunohistochemical and topographical findings)].
AB  - The objective of the present study was the comprehensive analysis of the
      postmortem changes in the lumbar intervertebral disks within different periods
      after death. A total of seven vertebromotor segments were distinguished in the
      lumbosacral region of the vertebral column based on the examination of 7 corpses.
      All these segments were divided into three groups in accordance with the
      prescription of death coming as follows: up to 12 hours (group 1), between 12 and
      24 hours (group 2), and between 24 and 36 hours (group 3) after death. The models
      of the segments thus obtained were subjected to the study by means of diffusion
      weighted MRI. The removed intervertebral disks were used for morphological and
      immunohistochemical investigations. The comparison of the diffusion coefficients
      (DI) revealed the significant difference between the intervertebral disks
      assigned to groups 1 and 2 (p<0.01). The number of the cells in the pulpal core,
      the vertebral end plate, and the fibrous ring in all the above groups of the
      intervertebral disks was significantly reduced (p<0.01). The analysis of the
      correlation dependence between cell density and diffusion coefficients has
      demonstrated the well apparent relationship between these characteristics of the
      intervertebral disks comprising groups 1 and 2. It is concluded that diffusion
      weighted MRI in the combination with the calculation of diffusion coefficients
      for the intervertebral disks provides a tool for diagnostics of prescription of
      death coming as confirmed by the results of the morphometric studies and
      immunohistochemical analysis.

PMID- 28766520
TI  - [The peculiarities of the relationship between the effector cells of the local
      immune system in the broncho-vascular barrier of the breast-fed infants
      presenting with certain acute respiratory viral infections].
AB  - : The acute respiratory viral infections (ARVI) are ranked among the most
      widespread diseases affecting the children in the early infancy. They account for
      60 to 85.4% of all infections recorded in the young children. AIM: The objective
      of the present study was to elucidate the peculiar features of the accumulation
      of the effector cells of the local immunity system and intercellular interplay in
      the broncho-vascular barrier of the breast-fed infants presenting with various
      ARVIs. MATERIAL AND METHODS: We undertook the analysis of 32 cases of infections
      caused by influenza A and B viruses and of the adenovirus infection verified by
      the immunofluorescence assay. The group of comparison was comprised of 10
      children presenting with congenial heart disease in the absence of the signs of
      inflammatory processes in the lungs. The tissue samples were harvested from the
      upper lobe of the lung at the level of the lobe bronchus and a terminal
      bronchiola. The materials for the histological study were prepared using the
      Romanovsky method. The effector cells were examined in the lamina propria of
      bronchial mucosa and the submucous layer. The morphometric analysis included
      direct counting the number of lymphocytes, mast cells, macrophages, plasmocytes,
      eosinophils, and neutrophils with the subsequent recalculation of the data thus
      obtained per unit volume of the connective tissue. The results of the
      morphometric analysis were subjected to the statistical treatment. RESULTS: The
      study has demonstrated that the young children suffering from a viral infection,
      regardless of the type of the causative factor, experience a change in the total
      number and the ratio of the effector cells at all the levels of the broncho
      vascular barrier.

PMID- 28766521
TI  - [The experimental and postmortem morphological characteristic of the chronic
      action of alcohol on the testicles].
AB  - The objective of the present study was to analyze the dynamics of the
      morphological changes that manifest themselves in the testicles of mature rats
      exposed to chronic alcohol intoxication over a period up to 6 months and to
      compare them with the analogous changes in the testicles of men who had had the
      long history of alcohol dependence and died with the pronounced symptoms of
      alcohol intoxication. The study has demonstrated the strong resemblance between
      the changes in the testes of men and animals including such as the dystrophic
      alteration of the spermatogenic epithelium, diffuse overgrowth of the connective
      tissue, well apparent signs of disturbed blood circulation, and suppression of
      spermatogenesis. However, these morphological changes in human testicles were
      more pronounced than in the rat gonads. In certain cases they underwent further
      fibrous transformation with the formation of well apparent hyalinosis foci. It is
      worthwhile to note that such morphological changes in the humans were not the
      specific consequences of the excessive alcohol consumption but reflected the
      collective influence of various toxic agents, with alcohol being one of the
      leading intoxicants.

PMID- 28766522
TI  - [The forensic medical significance of the igniting primer for the 18*45T
      cartridges of the 'Osa' pistol].
AB  - The objective of the present study was to obtain the ballistic characteristics of
      the igniting primer (electrical ignitor) for the 18*45T cartridges of the 'Osa'
      pistol produced by different manufacturers. The experiments included a series of
      shots fired from the 'Osa' pistol with the use of cartridges having an energy of
      85 Joules ('Novye oruzheinye tekhnologii', Ltd., Sergiev Posad) and 88 Joules
      ('A+A', Ltd, Tula). The shooting distance varied from the point blank range to 5,
      10, 20, 30, 40, and 50 cm. The targets were either the femoral soft tissue of the
      cut-off human lower extremity, white cotton fabric, and the 1-5 cm high gelatin
      cylinder 25 cm in diameter. The experiments have demonstrated that the igniting
      primer (electrical ignitor) for the cartridges manufactured by the 'Novye
      oruzheinye tekhnologii', Ltd., Sergiev Posad, served as an additional factor of
      the shot responsible for the penetrating power of the ammunition at a distance of
      50 cm. The data on the composition of metals used for the manufacturing of the
      igniting primers under consideration are presented.

PMID- 28766523
TI  - [The morphological diagnostics of the toxic effects of the smoking blends in the
      cases of fatal intoxication with pyrrolidinovalerophenone].
AB  - The objective of the present study was the development of the morphological
      criteria for the diagnostics of fatal intoxication with the herbal smoking blends
      (spices) using the samples of the biological materials obtained from the victims
      of pyrrolidinovalerophenone poisoning. The samples were taken from 13 autopsied
      cadavers of 11 men and 2 women at the age from 26 to 39 years based at the
      Astrakhan Regional Bureau of Forensic Medical Expertise during the period from
      21011 to 2015. The diagnosis of pyrrolidinvalerpphenon poisoning was verified to
      the letter. The materials obtained during the standard autopsy procedure were
      used for the forensic genetic studies in the combination with the mandatory
      routine forensic chemical investigations with the application of the gas
      chromatographic techniques. Polymorphism of the morphological picture was
      attributable to the differences in the chemical composition of the poisons and
      the combination of narcotic and alcoholic intoxication. The signs of chronic
      intoxication manifested themselves in the form of mixed gliosis and various
      lesions of brain neurons. The variety of clinical symptoms and the morphological
      picture of pyrrolidinovalerophenone poisoning are responsible for different forms
      of tanatogenesis which suggests the necessity of further research on the
      mechanisms underlying the toxic effects of herbal smoking blends.

PMID- 28766524
TI  - [The possibilities for sex determination based on the specific anatomical
      features of the human thyroid cartilage].
AB  - The objective of the present work was to study the specific morphological
      features in the structure of the human thyroid cartilage obtained from 35 men and
      35 women. The analysis and evaluation of 31 characteristics of the thyroid
      cartilage have demonstrated that its size in the men was bigger than in the women
      with the exception of the angle between the plates that was of a larger size in
      the women than in the men and showed the closest correlation with the sex. The
      majority of other characteristics of the thyroid cartilage measured in the study
      either strongly or moderately correlated with the sex which makes it possible to
      use these measurements for the purpose of personality identification during
      forensic medical expertise.

PMID- 28766525
TI  - [The possibilities for the use of the spectral analysis to overcome the
      incompatibility of the speech materials for the purpose of medical criminalistic
      identification of the speaker].
AB  - The objective of the present study was the formulation of the theoretical
      premises on which to base the approaches to the overcoming of the limitations not
      infrequently imposed on the sound records of the speech material of interest. The
      secondary objective was the development of the methods for this purpose. We
      analyzed the literature sources, the methodological instructive regulations, and
      the results of medical criminalistics investigations. The study has demonstrated
      that the spectral analysis of the speech materials provides a reliable tool for
      overcoming the incomplete (by force of different causes) compatibility between
      the initial phonograms and those under consideration for the purpose of forensic
      medical expertise with a view to the identification of personality of the
      speaker.

PMID- 28766526
TI  - [The development of the method for the determination of the low-molecular weight
      alcohol content in the specimens of the biological materials].
AB  - The objective of the present study was the development and metrological
      attestation of the method for the determination of concentrations of low
      molecular weight (C1-C4) alcohols and acetone in the biological materials, such
      as urine and blood including partially dehydrated blood. The method is based on
      the chromatographic analysis of the equilibrium vapour phase with the use of the
      static headspace autosampler. The calculations were carried out making use of the
      results obtained with the application of propanol-1 as the internal standard. In
      order to enhance the reliability of the identification of the analytes in the
      complex blood matrix, the two-channel configuration was employed that consisted
      of a single evaporator, passive flow division, two capillary columns of different
      polarity, and two flame ionization detectors. The proposed technique provided for
      the first time the unique possibility to perform the quantitative measurement of
      the internal standard in the starting specimen before the main analysis. The
      validated procedure for the quantitative determination of the alcohol
      concentration of blood samples with the reduced water content has been described.
      The present study made it possible to collect the total amount of relevant
      statistical data necessary to calculate the metrological characteristics of the
      method in question. The method was certified based at D.I. Mendeleev All-Russian
      Research Institute of Metrology under No 754/242-(01.00250)-2016.

PMID- 28766527
TI  - [The determination of 2,4-di-tret-butyl hydroxybenzene for the purpose of the
      chemical toxicological study of the biological materials].
AB  - The objective of this work was to study peculiarities of identification of 2,4-di
      tert-butyl hydroxybenzene (2,4-DTBHOB) in blood and the tissues of various organs
      with the use TLC, UR- and UV-spectrophotometry. The results of the study suggest
      the expediency of the application of ethylacetate as the extractive agent for the
      isolation of 2,4-DTBHOB from the biological materials. The optimal conditions for
      2,4-DTBHOB extraction by this method were developed based on the decontamination
      of the analyte by means of removal of the organic substances of biological
      matrices using the L 40/100 mcm sorbent columns with the hexan/dioxane mixture
      (8.5:1.5) as the mobile phase. The method for the determination of 2,4-di-tert
      butyl hydroxybenzene in the tissues of various organs (namely, liver) and blood
      has been developed. The proposed method allows to determine the minimal
      quantities of 2,4-DTBHOB present in the biological objects equivalent to 0.36 mg
      and 0.28 mg in the hepatic tissue and blood respectively.

PMID- 28766528
TI  - [The importance of marker proteins of the nervous tissue for morphological
      diagnostics of the craniocerebral injury].
AB  - The present review of the literature involves 50 publications concerning various
      substrates of importance as the biological markers of axonal damages with special
      reference to the secondary molecular and cellular mechanisms on which to base in
      vitro and in vivo modeling of the craniocerebral injury. The results of the
      investigations with the application of mass-spectrometry for the identification
      of the proteins specifically synthesized in response to the injury are presented;
      their biological functions are described. The use of the sequential microscopic
      imaging technique and the immunohistochemical methods made it possible to
      determine that the majority of the marker proteins are involved in the specific
      intracellular processes that are triggered in response to the traumatic impact
      including apoptosis, proliferation, formation of lamellipodia, axon regeneration,
      actin remodeling, cell migration and inflammation. In addition, a rise in the
      amount of intracellular actin-associated proteins has been observed. It is
      concluded that the investigations into the properties and the physiological role
      of beta-amyloid precursor protein (beta-APP) are of special value for the
      characteristic of nervous tissue damages and morphological diagnostics of the
      craniocerebral injury.

PMID- 28766529
TI  - [The coroner's autopsies in the Great Britain: the problems related to the
      quality of the studies, standardization, auditing, financial support and the
      approaches to their solution (part 2)].
AB  - This article extends the previous publication of the authors based on the
      analysis of the detailed report of the experts of the National Confidential
      Enquiry into Patient Outcome and Death program (NCEPOD) issued in the Great
      Britain in 2006. The analysis has demonstrated that all autopsy studies should
      invariably involve measurement of the corpse length and weight (including body
      mass index) as well as the detailed description of all injuries to the body (or
      references to their absence). All autopsy studies should be carried out only by a
      medical professional (e.g. a pathologist, histologist, forensic medical expert,
      etc.). The thorough examination of the cadaver is mandatory prior to
      evisceration. The maximum scope of the examination of all body cavities with the
      comprehensive description of all internal organs and systems is compulsory.
      Putrefaction and decomposition of the corpse can not be regarded as a
      justification for its perfunctory ('restricted') inspection; on the contrary,
      these dictate the necessity of a more careful examination with the compulsory
      description of all organs and body systems as well as harvesting biological
      fluids and tissues for the laboratory analyses (including histological,
      toxicological, and other relevant studies).

PMID- 28766530
TI  - [The commission/comprehensive forensic medical expertise with the participation
      of the medical professionals].
AB  - The present article deals with the categorization of the forensic medical
      expertises with respect to their ranking as commission and/or comprehensive ones.
      The arguments for and against such an approach and interpretation are presented.

PMID- 28766531
TI  - [The academic discipline 'forensic medicine' as an important component of the
      training of dental practitioners].
AB  - The authors discuss the conceptual issues of the academic program designed to
      teach forensic medicine to the students of the stomatological faculties of
      educational medical institutions. The program has been elaborated in conformity
      with the federal state educational standard of higher professional education in
      the speciality stomatology'. It defines the goals and objectives of this
      discipline, the scope of its competences, the subject matter and the content, the
      requirements to the studies and educational work, control over the level of its
      success, academic progress, and other aspects of the training activities, with
      special emphasis being placed on the formation of the general professional
      competence of the students to enable them to work independently after they
      graduated from the institute. The program takes into consideration the latest
      achievements in forensic medical science and their practical applications. Much
      attention is given to the organizational and processual aspects of forensic
      medicine, thanatology, general and special traumatology, mechanical asphyxia,
      effects of the environmental factors, intoxication, forensic medical expertise of
      living subjects and material evidence.

PMID- 28766532
TI  - [The Grand Prince G.A. Romanov and the diagnostic capabilities of XIX century
      medicine].
AB  - This article is devoted to the medical aspects of the biography of the Grand
      Prince Georgiy Romanov, the younger brother of Nikolas II, the Russian Emperor.
      It reports the results of the analysis of the formerly unpublished documents
      stored in the funds of the Russian State Historical Archive (RGIA). The authors
      present the data characterizing the level of medical care provided to the
      patients in Russia of that time. In addition, they describe the specific
      morphological patterns of pulmonary tuberculosis which affected the Crown Prince
      and became the cause of his death.

PMID- 28766533
TI  - [The results of the scientific and practical conference 'The topical problems of
      forensic medicine and medical law', Moscow, 23.12. 2016].

PMID- 28766534
TI  - [Clinical features of essential thrombocythemia and primary myelofibrosis,
      depending on the molecular characteristics of disease].
AB  - The aim of the present paper was to evaluate the clinical features and risk of
      thrombotic events (TE) in patients with essential thrombocythemia (ET) and
      primary myelofibrosis (PMF), depending on the molecular characteristics of
      disease. Clinical data and laboratory parameters were analyzed in 50 ET patients
      and 50 PMF ones who had been followed up at the Department for Standardization of
      Treatments, National Research Center for Hematology, Ministry of Health of the
      Russian Federation, from February 2015 to September 2016. The patients with ET
      and those with PMF were found to have a high risk of TE. The risk for TE in the
      patients with ET is higher (24% in the entire group) than in those with PMF (14%
      in the study group). In ET, there is a high thrombosis risk in the detection of
      JAK2 and CALR gene mutations as compared with triple-negative cases. The PMF
      patients with JAK2 V617F mutations are at high risk for TE compared to those who
      are CALR mutation carriers and in triple-negative cases. There was no significant
      association of TE with high thrombocytosis. A factor, such as age, was found to
      be of no negative prognostic value in the patients with PMF.

PMID- 28766535
TI  - [Adult B-cell acute lymphoblastic leukemias: Conclusions of the Russian
      prospective multicenter study ALL-2009].
AB  - AIM: To analyze the efficiency and reproducibility of the ALL-2009 protocol
      within the Russian prospective multicenter study based on different principles of
      cytostatic effects (non-intensive, but continuous cytotoxic treatment and a small
      number of allogeneic hematopoietic stem cells). SUBJECTS AND METHODS: The ALL
      2009 (NCT01193933) study conducted in April 2009 to December 2016 included 194
      patients (95 males and 99 females) aged 15 to 55 years (median age 28 years) with
      Ph-negative B-cell acute lymphoblastic leukemia (ALL). There was early pre-B-cell
      ALL in 54 patients, common ALL in 101, pre-B ALL in 39, initial leukocytosis in
      9.4.109/l (0.4-899.0), lactate dehydrogenase in 901 IU (31-13 059), an initial
      central nervous system lesion in 17 (8.7%), mediastinal injury in 3 (1.5%), and
      splenomegaly in 111 (57.2%). The results of standard cytogenetic analysis are
      known in 113 (60.4%) patients. Normal karyotypes were detected in 49 (54.5%) out
      of the patients; t(4;11) in 9 (5.4%), t(1;19) in 2 (1.2%), and other karyotypic
      abnormalities in 53 (46.9%). Thirteen (7.8%) patients underwent allogeneic
      hematopoietic stem cell transplantation in first complete remission (CR); their
      proportion did not differ in the federal and regional centers. RESULTS: The
      frequency of CR achievement was the same in the federal and regional centers and
      generally amounted to 87.5%. Early (8.8%) and CR (9.6%) mortality rates remained
      high despite the low aggressiveness of cytotoxic action, necessitating the
      improvement of auxiliary treatment. The five-year overall survival (OS) rates
      vary considerably in the federal and regional centers (72.6 and 43.8%), the
      relapse-free survival (RFS) (70.2 and 53.4%) and recurrence risk (23.1 and 36.5%)
      are comparable. This suggests that the non-intensive, but continuous exposure
      principle built in the ALL-2009 protocol makes it possible to reproduce the
      envisaged treatment program and to achieve satisfactory results. CONCLUSION: The
      ALL-2009 protocol allows both the federal and regional centers to obtain the long
      term results comparable with those of current foreign studies: OS (54.2%), RFS
      (56.5%); and relapse risk (35.4%). Multivariate analysis has identified age (over
      30 years), initial leukocytosis (30.109/l and more) and t(4;11) among the main
      clinical prognostic factors. Gene mutation detection evaluated in a small number
      of patients (8/36) is not a poor prognostic sign. There is a need for further
      investigations with centralized evaluation of the mutation status of leukemic
      cells and the clearance of minimal residual disease.

PMID- 28766536
TI  - [Absolute numbers of peripheral blood CD34+ hematopoietic stem cells prior to a
      leukapheresis procedure as a parameter predicting the efficiency of stem cell
      collection].
AB  - AIM: To identify a parameter predicting a collection of at least 2.106 CD34+
      hematopoietic stem cells (HSC)/kg body weight per leukapheresis (LA) procedure.
      SUBJECTS AND METHODS: The investigation included 189 patients with hematological
      malignancies and 3 HSC donors, who underwent mobilization of stem cells with
      their subsequent collection by LA. Absolute numbers of peripheral blood
      leukocytes and CD34+ cells before a LA procedure, as well as a number of CD34+
      cells/kg body weight (BW) in the LA product stored on the same day were
      determined in each patient (donor). RESULTS: There was no correlation between the
      number of leukocytes and that of stored CD34+ cells/kg BW. There was a close
      correlation between the count of peripheral blood CD34+ cells prior to LA and
      that of collected CD34+ cells calculated with reference to kg BW. CONCLUSION: The
      optimal absolute blood CD34+ cell count was estimated to 20 per ul, at which a LA
      procedure makes it possible to collect 2.106 or more CD34+ cells/kg BW.

PMID- 28766537
TI  - [Multiple myeloma: Maintenance therapy after autologous hematopoietic stem cell
      transplantation, depending on minimal residual disease].
AB  - AIM: To determine the efficiency of maintenance therapy with bortezomib in
      patients with multiple myeloma (MM) who have achieved complete remission (CR)
      after autologous hematopoietic stem cell (auto-HSCT), depending on the presence
      of minimal residual disease (MRD). SUBJECTS AND METHODS: In January 2014 to
      February 2016, fifty-two MM patients (19 men and 33 women) aged 24 to 66 years
      (median 54 years), who had achieved CR after auto-HSCT, were randomized to
      perform maintenance therapy with bortezomib during a year. On day 100 after auto
      HSCT, all the patients underwent immunophenotyping of bone marrow plasma cells by
      6-color flow cytometry to detect MRD. Relapse-free survival (RFS) was chosen as a
      criterion for evaluating the efficiency of maintenance therapy. RESULTS: After
      auto-HSCT, MRD-negative patients had a statistically significantly higher 2-year
      RFS rate than MRD-positive patients: 52.9% (95% confidence interval (CI), 35.5 to
      70.5%) versus 37.2% (95% CI, 25.4 to 49.3%) (p=0.05). The presence of MRD
      statistically significantly increased the risk of relapse (odds ratio 1.7; 95%
      CI, 1.2 to 3.4; p=0.05). Two-year cumulative risk of relapse (using the Kaplan
      Meier) after auto-HSCT did not statistically significantly differ in MRD-negative
      patients receiving (n=15) and not receiving (n=10) maintenance therapy with
      bortezomib (p=0.58). After completion of maintenance treatment, 42% of the MRD
      positive patients achieved a negative status. In the MRD-positive patients who
      had received maintenance therapy, the average time to recurrence was 5 months
      longer than that in the naive patients: 17.3 versus 12.3 months. CONCLUSION: The
      MRD status determined in MM patients who have achieved CR after auto-HSCT is an
      important factor for deciding on the use of maintenance therapy.

PMID- 28766538
TI  - [Prognostic value of 1q21 amplification in multiple myeloma].
AB  - AIM: To determine the prevalence of amp1q21 and its relationship to the clinical
      manifestations of multiple myeloma (MM). SUBJECTS AND METHODS: In December 2009
      to March 2016, a total 134 patients aged 30 to 81 years (median 57 years)
      underwent a pretreatment FISH-study of bone marrow (BM) with centromeric and
      locus-specific DNA probes to identify amp1q21, t(11;14), t(4;14), t(14;16),
      t(14;20), t(6;14), trisomies of chromosomes 5, 9, 15, del13q14, del17p13/TP53,
      and t(8q24)/cMYC. Induction therapy with bortezomib-containing cycles was
      performed. Autologous stem cell transplantation was carried out in 48 patients.
      The median follow-up of patients was 19.3 months (3.2-77.4 months). Disease
      progression was diagnosed in 69 (51.5%) patients; 12 patients also underwent FISH
      study during disease progression. RESULTS: At the onset of MM, amp1q21 was
      detected in 53 (39.6%) patients. The overall 5-year survival rate in patients
      with amp1q21 was almost 2 times lower than that in those without amp1q21 (43.5
      and 79.4%, respectively; p=0.07). The overall 5-year survival rate in patients
      with one extra copy of 1q21 (only 3 copies) was 67.3%, that in those with 2 or
      more extra copies of 1q21 (only 4-7 copies) was 20.9% (p=0.0016). Nine (75%) of
      the 12 patients examined during disease progression were found to have amp1q21: 2
      cases were detected in the period of progression to have amp1q21 in its absence
      at disease onset; 7 cases had amp1q21 both at MM onset and progression; however,
      the number of copies of 1q21 was unchanged. CONCLUSION: Amp1q21 is one of the
      most common chromosomal abnormalities in patients with new-onset MM and may
      appear in the course of disease progression. The presence of amp1q21 is an
      important prognostic factor and must have to be included in the diagnostic study
      both at disease onset and progression.

PMID- 28766539
TI  - [Analysis of VEGF-A/VEGFR1/VEGFR2 gene expression in patients with
      myelodysplastic syndrome].
AB  - AIM: To assess the significance of gene expression of the vascular endothelial
      growth factor-A (VEGF-A) and its interacting receptors VEGFR1 and VEGFR2 as
      potential diagnostic and prognostic molecular markers in patients with
      myelodysplastic syndrome (MDS). MATERIAL AND METHODS: A real time polymerase
      chain reaction (RT-PCR) assay was used to investigate the gene expression of VEGF
      A, VEGFR1, and VEGFR2 in the mononuclear cell fractions obtained from 24 patients
      with MDS. RESULTS: The expression of the 3 genes was identified in all the
      patients examined. There was the highest expression level of the VEGF-A gene
      (p<0.0001), whereas the expression of the VEGFR1 gene was higher than that of the
      VEGFR2 gene (p<0.001). The expression of the VEGF-A gene proved to be higher in
      patients at a higher risk of acute leukemia and positively correlated with the
      expression levels of the VEGFR1 gene (p<0.05) rather than that of the VEGFR2
      gene. At the same time, patients with higher VEGFR1 gene expression had
      significantly lower overall survival rates (r=-0.5; p<0.05). Patients with
      intermediate-2 or high-risk acute leukemia showed an increase in the average
      expression levels of VEGF-A and VEGFR1 and a reduction in VEGFR2 expression.
      CONCLUSION: This investigation revealed correlations between the number of blast
      cells in patients with MDS and the expression levels of the VEGF-A gene and
      between the overall survival of patients with MDS and the expression levels of
      the VEGFR1 gene rather than those of the VEGF-A and VEGFR2 genes.

PMID- 28766540
TI  - [Leukemization of follicular lymphoma: The features of diagnostic and clinical
      course of a rare form of the disease].
AB  - AIM: To characterize a group of patients with follicular lymphoma (FL) with
      leukemization and to evaluate the efficiency of different therapy options (R
      CHOP/R-FMC/high-dose chemotherapy (HDCT)). SUBJECTS AND METHODS: 18 (7.2%) out of
      250 patients diagnosed with FL, who were examined and treated at the National
      Research Center for Hematology, Ministry of Health of the Russian Federation,
      were found to have leukemic FL (tumor cells in the peripheral blood smears were
      detected by cytology and flow cytofluorometry. Eight of the 18 patients had
      extranodal foci of involvement: lung, stomach, spleen, lumbar muscles, upper jaw,
      and vertebrae. Bone marrow was involved in 17 of the 18 patients. Tumor biopsy
      specimens displayed a morphological pattern of indolent FL in the majority of
      patients (10 of the 18 patients had cytological grade 1-2 tumors and 14 patients
      had a nodular or nodular-diffuse tumor growth pattern). The patients underwent R
      CHOP/R-FMC) or HDCT cycles as first-line therapy, followed by autologous stem
      cell transplantation (auto-SCT). RESULTS: The median follow-up was 66 months
      (range 12-217 months). The 5-year overall survival (OS) and progression-free
      survival (PFS) rates were 70% (10% SEM) and 35% (15% SEM), respectively. The
      median OS was not reached; the median PFS was 3 years. CONCLUSION: Leukemic FL is
      characterized by low OS and PFS rates. The most effective chemotherapy regimens
      were R-CHOP, followed by HDCT and auto-SCT in first remission or R-FMC. These
      cycles can to a greater extent achieve a complete eradication of the bone marrow
      tumor clone. Due to the relapsing course of FL and the aggressiveness of leukemic
      FL, it is expedient to carry out auto-SCT in first remission.

PMID- 28766541
TI  - [Use of crizotinib for refractory ALK-positive lymphomas].
AB  - AIM: To evaluate the safety and efficacy of crizotinib used in pediatric patients
      with relapsed or refractory ALK-positive anaplastic large-cell lymphoma (ALCL).
      SUBJECTS AND METHODS: The paper describes the experience with crizotinib used in
      8 patients with refractory ALK-ALCL before and after allogeneic hematopoietic
      stem cell transplantation (HSCT). RESULTS: All the 8 (100%) patients treated with
      crizotinib were recorded to have complete responses, including complete metabolic
      ones (tumor disappearance as evidenced by positron emission tomography
      (PET)/computed tomography. CONCLUSION: Low and manageable toxicity of crizotinib
      and complete PET-negative responses in patients with resistant ALK lymphomas
      favor the need to test the drug as first-line therapy, by possibly decreasing the
      intensification of chemotherapy.

PMID- 28766542
TI  - [Efficacy of a bendamustine and rituximab combination in first-line therapy for
      chronic lymphocytic leukemia: Results of the BEN-001 study].
AB  - AIM: To evaluate the efficacy and safety of the BR regimen containing
      bendamustine in patients with chronic lymphocytic leukemia (CLL) who have not
      previously received specific therapy. SUBJECTS AND METHODS: The results of the
      Russian prospective observational multicenter study BEN-001 (2012-2015) covering
      196 CLL patients from 34 centers of the Russian Federation were analyzed. The
      diagnosis was confirmed by the results of peripheral blood lymphocyte
      immunophenotyping. A centralized approach was employed to make IGHV gene
      mutational status analysis, FISH examination, and minimal residual disease
      according to standardized methods. Quality-of-life (QOL) indicators were
      estimated using the EQ-5D and FACT-Leu questionnaires. Survival rates were
      calculated applying by the Kaplan-Meier method. RESULTS: The patients' median age
      was 61 years. 41% of patients had a decline in estimated creatinine clearance
      less than 70 ml/min/1.73 m2. The combination of bendamustine and rituximab could
      achieve a common response in 83.2% of the patients, including complete remission
      in 59.7%. Eradication of minimal residual disease was achieved in 23 (27.4%) of
      84 patients. Two-year progression-free survival rates were 85.9%. The QOL
      indicators were noted to be improved during the treatment. CONCLUSION: The
      investigation shows the good tolerability of bendamustine when it is used in
      clinical practice. Due to the high cost of new drugs (ibrutinib, obinutuzumab,
      ofatumumab, etc.) and toxicity of the FCR regimen, the combination including
      bendamustine can be the best first-line therapy option for all CLL patients,
      regardless of their age and comorbidity.

PMID- 28766543
TI  - [Bone marrow involvement in primary mediastinal B-cell lymphoma].
AB  - Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct type of large B
      cell lymphoma. In this type of the disease, the neoplastic process is located in
      the anterior and superior mediastinum, frequently with compression of the
      superior vena cava and with tumor invasion into the adjacent organs and tissues:
      the pericardium, lung, pleura, etc. Despite the fact that in PMBCL progression,
      there may be involvement of extranodal organs, such as the kidney, adrenal
      glands, liver, and central nervous system, bone marrow (BM) injury is generally
      absent. Since BM injury in patients with diffuse large B-cell lymphoma is an
      independent poor prognostic indicator, there is reason to believe that BM
      involvement in PMBCL affects the prognosis. These cases may need intensified
      induction therapy followed by autologous hematopoietic stem cell transplantation;
      and BM injury should be monitored during the therapy. The paper gives reports of
      clinical cases of bone marrow involvement in 2 PMBCL patients treated at the
      National Research Center for Hematology, Ministry of Health of the Russian
      Federation.

PMID- 28766544
TI  - [EBV-positive central nervous system lymphoproliferative disease associated with
      immunosuppression after organ transplantation: Long-term remission without
      chemotherapy].
AB  - Primary central nervous system (CNS) lymphomas account for 13-20% of the
      posttransplant lymphoproliferative disorders (PTLD) and rank among the most
      aggressive conditions. Reduction of immunosuppressive therapy should be mandatory
      to treat PTLD, but this is rarely used as the only therapy option. Chemotherapy
      regimens for PTLD involving the CNS most commonly include high-dose rituximab and
      high-dose methotrexate and/or cytarabine. The efficiency only of discontinuation
      of immunosuppressive therapy for PTLD does not exceed 5-10%, but there are no
      literature data on its efficiency for PTLD involving the CNS. The paper describes
      a clinical case of achieving long-term remission in a female patient with Epstein
      Barr virus (EBV)-positive diffuse large B-cell lymphoma involving the central
      nervous system, associated with immunosuppression after kidney transplantation
      from a related donor, in the absence of chemotherapy during immunosuppressive
      therapy discontinuation and transplantectomy.

PMID- 28766545
TI  - [Thrombotic events in patients with hemophilia].
AB  - The paper describes 4 clinical cases of thrombotic events (pulmonary embolism,
      deep vein thrombophlebitis, acute myocardial infarction, ischemic stroke) that
      have occurred in patients with hemophilia. It discusses the possible causes of
      their development and methods for their prevention and treatment. Controlled
      natural hypocoagulation, in which the dose of an administered deficient factor
      decreases to such an extent that in order to maintain the safe level of
      hypocoagulation (plasma factor activity is 15-20%; activated partial
      thromboplastin time is 1.5-2 times normal values), is proposed as one of the
      treatment options.

PMID- 28766546
TI  - [Diffuse large B-cell lymphoma with concomitant c-MYC and BCL6 gene
      rearrangements with primary skin involvement: A case report and a review of
      literature].
AB  - Double-hit lymphoma (DHL) is a rare aggressive B-cell lymphoma with concomitant c
      MYC, BCL2 or BCL6 gene rearrangements, which is characterized by the high
      frequency of extranodal lesions and by resistance to chemotherapy. The median
      survival does not exceed 18 months in patients with this disease. The majority of
      DHL is represented by s-MYC/BCL2 cases. The combination of c-MYC/BCL6 occurs
      rarely (5-8%). The paper describes a case of DHL with concomitant c-MYC and BCL6
      gene rearrangements, which mimics diffuse large B-cell lymphoma, leg-type.

PMID- 28766547
TI  - [Breast implant-associated anaplastic large-cell lymphoma: A case report and a
      review of literature].
AB  - Breast implant-associated anaplastic large-cell lymphoma will be identified as a
      separate nosological entity in the 2017 adapted WHO classification due to
      differences in its clinical presentations, pathogenesis, and prognosis with those
      of nodal and cutaneous anaplastic large-cell lymphomas. The paper gives a review
      of the literature and describes the authors' own clinical case of common breast
      implant-associated anaplastic large-cell lymphoma involving breast tissue,
      axillary lymph nodes, anterior chest muscles, and bone marrow. The treatment
      policy chosen by the authors could achieve complete remission.

PMID- 28766548
TI  - [Hairy cell leukemia and pregnancy].
AB  - The paper presents experience in following up and treating hairy cell leukemia
      (HCL) during pregnancy. The combination of HCL and pregnancy was observed in 5
      patients. The patients' median age was 35 years (range, 28-42 years). The
      diagnosis of HCL was based on a conventional examination protocol: clinical blood
      analysis with the morphological assessment of lymphocytes, a myelogram and
      trepanobiopsy, immunophenotypic analysis of lymphocytes or bone marrow (in all
      the patients), cytochemical determination of tartrate-resistant acid phosphatase
      in 3 patients, and identification of BRAFV600E mutation in 3 patients. Three
      pregnant women were treated for HCL in the postpartum period. In one patient with
      HCL, pregnancy was seen in remission after treatment with cladribine. In one
      patient with HCL detected at 11 weeks' gestation, interferon-alpha therapy during
      the second trimester of pregnancy was performed for increased cytopenia, which
      was followed by cladribine therapy after delivery. Pregnancy and delivery were
      uncomplicated in all the patients; 3 patients had vaginal delivery and 2 patients
      underwent cesarean section. All infants were healthy, with no developmental
      abnormalities during a follow-up period of 6-140 months (median 30 months). All
      the patients with HCL are currently in remission: 4 patients in first remission
      at a follow-up of 10 to 48 months (median 15 months) and one patient in second
      remission at a follow-up of 88 months. Possible observational tactics is possible
      when HCL is detected during pregnancy. Treatment of HCL during pregnancy is
      necessary in cases of deep or progressive cytopenia and/or splenomegaly. The use
      of interferon-alpha or splenectomy is preferable.

PMID- 28766549
TI  - [Analysis of inpatient care for HIV-positive patients with malignant lymphomas
      and hepatitis over 5 years (2011-2015) at the A.S.Loginov Moscow Clinical
      Research Center, Moscow Healthcare Department].
AB  - The authors give their own data in the first Russian publication on 170 patients
      with lymphomas and hepatitis concurrent with HIV infection, on the distribution
      of therapy regimens by nosological entities and the number of deaths.
      Conventional protocols and programs were used for diagnosis and treatment. All
      the patients received highly active antiretroviral therapy. Lymphoma was treated
      according to the conventional programs using rituximab in people without
      hepatitis B. Aggressive lymphomas, such as diffuse large B-cell lymphoma, Burkitt
      lymphoma, and plasmablastic lymphoma, were identified in most patients. Hodgkin's
      lymphoma is the matter of a separate study; it differs in its pathogenesis from
      other lymphomas. The rate of coinfection with hepatitis was high in the entire
      group of patients with lymphomas. The major prognostic indicators included low
      CD4 T-cell counts (less than 50), stage IVB lymphoma, and hepatitis. Complete
      remissions were achieved in 40% of patients. Forty-one (24%) patients died.

PMID- 28766550
TI  - [Current approaches to treating of patients with multiple myeloma with renal
      failure: Questions and proofs].
AB  - Renal failure (RF) is detected in 20-30% of patients at the onset of multiple
      myeloma (MM), in 50% of patients during its progression. The advent of new,
      highly effective agents has considerably expanded the possibilities of treatment
      in MM patients. Unfortunately, patients with RF, especially those with severe RF,
      were not included in the majority of investigations. The available data are based
      on the results of treatment in small groups of patients generally without the
      morphological identification of nephropathies, with varying severity of RF, which
      explains significant differences in renal response rates. This review analyzes
      the results of the most important studies and gives recommendations for treatment
      in accordance with national and international standards.

PMID- 28766551
TI  - Mutation in the COX4I1 gene is associated with short stature, poor weight gain
      and increased chromosomal breaks, simulating Fanconi anemia.
AB  - We describe a novel autosomal recessive form of mitochondrial disease in a child
      with short stature, poor weight gain, and mild dysmorphic features with highly
      suspected Fanconi anemia due to a mutation in COX4I1 gene. Whole Exome Sequencing
      was performed then followed by Sanger confirmation, identified a K101N mutation
      in COX4I1, segregating with the disease. This nuclear gene encodes the common
      isoform of cytochrome c oxidase (COX) subunit 4 (COX 4-1), an integral regulatory
      part of COX (respiratory chain complex IV) the terminal electron acceptor of the
      mitochondrial respiratory chain. The patient's fibroblasts disclosed decreased
      COX activity, impaired ATP production, elevated ROS production, decreased
      expression of COX4I1 mRNA and undetectable (COX4) protein. COX activity and ATP
      production were restored by lentiviral transfection with the wild-type gene. Our
      results demonstrate the first human mutation in the COX4I1 gene linked to
      diseases and confirm its role in the pathogenesis. Thus COX4I1 mutations should
      be considered in any patient with features suggestive of this diagnosis.

PMID- 28766552
TI  - Recontacting in clinical practice: the views and expectations of patients in the
      United Kingdom.
AB  - This paper explores the views and expectations of patients concerning
      recontacting in clinical practice. It is based on 41 semi-structured interviews
      conducted in the United Kingdom. The sample comprised patients or parents of
      patients: without a diagnosis; recently offered a test for a condition or carrier
      risk; with a rare condition; with a variant of unknown significance - some of
      whom had been recontacted. Participants were recruited both via the National
      Health Service (NHS) and through online, condition-specific support groups. Most
      respondents viewed recontacting as desirable, however there were different
      opinions and expectations about what type of new information should trigger
      recontacting. An awareness of the potential psychological impact of receiving new
      information led some to suggest that recontacting should be planned, and tailored
      to the nature of the new information and the specific situation of patients and
      families. The lack of clarity about lines of responsibility for recontacting and
      perceptions of resource constraints in the NHS tended to mitigate respondents'
      favourable positions towards recontacting and their preferences. Some respondents
      argued that recontacting could have a preventative value and reduce the cost of
      healthcare. Others challenged the idea that resources should be used to implement
      formalised recontacting systems - via arguments that there are 'more pressing'
      public health priorities, and for the need for healthcare services to offer care
      to new patients.

PMID- 28766553
TI  - Regulatory T cells with superior immunosuppressive capacity emigrate from the
      inflamed colon to draining lymph nodes.
AB  - Foxp3+ Regulatory T cells (Tregs) play a critical role in the maintenance of
      colon homeostasis. Here we utilized photoconvertible KikGR mice to track immune
      cells from the caecum and ascending (proximal) colon in the steady state and DSS
      induced colitis. We found that Tregs from the proximal colon (colonic migratory
      Tregs) migrated exclusively to the distal part of mesenteric lymph nodes (dMLN)
      in an S1PR1-dependent process. In the steady state, colonic migratory CD25+ Tregs
      expressed higher levels of CD103, ICOS, LAG3 and CTLA-4 in comparison with pre
      existing LN Tregs. Intestinal inflammation led to accelerated Treg replacement in
      the colon, bidirectional Treg migration from the colon to dMLN and vice versa, as
      well as increases in Treg number, proliferation and expression of
      immunosuppressive molecules. This was especially apparent for CD25 very high
      Tregs induced in colitis. Furthermore, colonic migratory Tregs from the inflamed
      colon included more interleukin (IL)-10 producing cells, and demonstrated greater
      inhibition of T-cell proliferation in comparison with pre-existing LN Tregs.
      Thus, our results suggest that Tregs with superior immunosuppressive capacity are
      increased both in the colon and dMLN upon inflammation. These Tregs recirculate
      between the colon and dMLN, and are likely to contribute to the downregulation of
      intestinal inflammation.

PMID- 28766554
TI  - Campylobacter jejuni impairs sodium transport and epithelial barrier function via
      cytokine release in human colon.
AB  - Campylobacter jejuni is the most prevalent cause of foodborne bacterial enteritis
      worldwide. Patients present with diarrhea and immune responses lead to
      complications like arthritis and irritable bowel syndrome. Although studies exist
      in animal and cell models, we aimed at a functional and structural
      characterization of intestinal dysfunction and the involved regulatory mechanisms
      in human colon. First, in patients' colonic biopsies, sodium malabsorption was
      identified as an important diarrheal mechanism resulting from hampered epithelial
      ion transport via impaired epithelial sodium channel (ENaC) beta- and gamma
      subunit. In addition, barrier dysfunction from disrupted epithelial tight
      junction proteins (claudin-1, -3, -4, -5, and -8), epithelial apoptosis, and
      appearance of lesions was detected, which cause leak-flux diarrhea and can
      perpetuate immune responses. Importantly, these effects in human biopsies either
      represent direct action of Campylobacter jejuni (ENaC impairment) or are caused
      by proinflammatory signaling (barrier dysfunction). This was revealed by
      regulator analysis from RNA-sequencing (cytometric bead array-checked) and
      confirmed in cell models, which identified interferon-gamma, TNFalpha, IL-13, and
      IL-1beta. Finally, bioinformatics' predictions yielded additional information on
      protective influences like vitamin D, which was confirmed in cell models. Thus,
      these are candidates for intervention strategies against C. jejuni infection and
      post-infectious sequelae, which result from the permissive barrier defect along
      the leaky gut.

PMID- 28766557
TI  - Usefulness of motion sensors to estimate energy expenditure in children and
      adults: a narrative review of studies using DLW.
AB  - This corrects the article DOI: 10.1038/ejcn.2017.2.

PMID- 28766555
TI  - The TLR9 agonist MGN1703 triggers a potent type I interferon response in the
      sigmoid colon.
AB  - Toll-like receptor 9 (TLR9) agonists are being developed for treatment of
      colorectal and other cancers, yet the impact of these drugs on human intestines
      remains unknown. This, together with the fact that there are additional potential
      indications for TLR9 agonist therapy (e.g., autoimmune and infectious diseases),
      led us to investigate the impact of MGN1703 (Lefitolimod) on intestinal
      homeostasis and viral persistence in HIV-positive individuals. Colonic sigmoid
      biopsies were collected (baseline and week four) from 11 HIV+ individuals on
      suppressive antiretroviral therapy, who received MGN1703 (60 mg s.c.) twice
      weekly for 4 weeks in a single-arm, phase 1b/2a study. Within sigmoid mucosa,
      global transcriptomic analyses revealed 248 modulated genes (false discovery
      rate<0.05) including many type I interferon (IFN)-stimulated genes. MGN1703
      increased the frequencies of cells exhibiting MX1 (P=0.001) and ISG15 (P=0.014)
      protein expression. No changes were observed in neutrophil infiltration
      (myeloperoxidase; P=0.97). No systematic effect on fecal microbiota structure was
      observed (analysis of similarity Global R=-0.105; P=0.929). TLR9 expression at
      baseline was inversely proportional to the change in integrated HIV DNA during
      MGN1703 treatment (P=0.020). In conclusion, MGN1703 induced a potent type I IFN
      response, without a concomitant general inflammatory response, in the intestines.

PMID- 28766558
TI  - The effect of L-arginine supplementation on body composition and performance in
      male athletes: a double-blinded randomized clinical trial.
AB  - This corrects the article DOI: 10.1038/ejcn.2016.266.

PMID- 28766559
TI  - Long-term treatment of phenylketonuria with a new medical food containing large
      neutral amino acids.
AB  - This corrects the article DOI: 10.1038/ejcn.2016.166.

PMID- 28766556
TI  - Antigen-specific regulatory T-cell responses to intestinal microbiota.
AB  - The mammalian gastrointestinal tract can harbor both beneficial commensal
      bacteria important for host health, but also pathogenic bacteria capable of
      intestinal damage. It is therefore important that the host immune system mount
      the appropriate immune response to these divergent groups of bacteria-promoting
      tolerance in response to commensal bacteria and sterilizing immunity in response
      to pathogenic bacteria. Failure to induce tolerance to commensal bacteria may
      underlie immune-mediated diseases such as human inflammatory bowel disease. At
      homeostasis, regulatory T (Treg) cells are a key component of the tolerogenic
      response by adaptive immunity. This review examines the mechanisms by which
      intestinal bacteria influence colonic T-cells and B-cell immunoglobulin A (IgA)
      induction, with an emphasis on Treg cells and the role of antigen-specificity in
      these processes. In addition to discussing key primary literature, this review
      highlights current controversies and important future directions.

PMID- 28766560
TI  - Radiofrequency electromagnetic field exposure in everyday microenvironments in
      Europe: A systematic literature review.
AB  - The impact of the introduction and advancement in communication technology in
      recent years on exposure level of the population is largely unknown. The main aim
      of this study is to systematically review literature on the distribution of
      radiofrequency electromagnetic field (RF-EMF) exposure in the everyday
      environment in Europe and summarize key characteristics of various types of RF
      EMF studies conducted in the European countries. We systematically searched the
      ISI Web of Science for relevant literature published between 1 January 2000 and
      30 April 2015, which assessed RF-EMF exposure levels by any of the methods: spot
      measurements, personal measurement with trained researchers and personal
      measurement with volunteers. Twenty-one published studies met our eligibility
      criteria of which 10 were spot measurements studies, 5 were personal measurement
      studies with trained researchers (microenvironmental), 5 were personal
      measurement studies with volunteers and 1 was a mixed methods study combining
      data collected by volunteers and trained researchers. RF-EMF data included in the
      studies were collected between 2005 and 2013. The mean total RF-EMF exposure for
      spot measurements in European "Homes" and "Outdoor" microenvironments was 0.29
      and 0.54 V/m, respectively. In the personal measurements studies with trained
      researchers, the mean total RF-EMF exposure was 0.24 V/m in "Home" and 0.76 V/m
      in "Outdoor". In the personal measurement studies with volunteers, the population
      weighted mean total RF-EMF exposure was 0.16 V/m in "Homes" and 0.20 V/m in
      "Outdoor". Among all European microenvironments in "Transportation", the highest
      mean total RF-EMF 1.96 V/m was found in trains of Belgium during 2007 where more
      than 95% of exposure was contributed by uplink. Typical RF-EMF exposure levels
      are substantially below regulatory limits. We found considerable differences
      between studies according to the type of measurements procedures, which precludes
      cross-country comparison or evaluating temporal trends. A comparable RF-EMF
      monitoring concept is needed to accurately identify typical RF-EMF exposure
      levels in the everyday environment.

PMID- 28766561
TI  - Editorial: Management of the Small Asymptomatic Pancreatic Cyst: Somehow Along
      the Way We Forgot About the Patient.
AB  - The incidentally identified pancreatic cyst is an increasing burden for both
      physicians and patients alike. Although we recognize that most of these lesions
      are benign and may not progress, a subset of these lesions are premalignant, may
      have frank cancer, and may progress over time. Most occur in older patients who
      have associated comorbidity. Recent studies highlight neoplastic features of
      these cysts that when present may warrant surgery or close long-term follow-up;
      however, there has been little study on the natural history factoring in patient
      comorbidity and pancreatic cancer-free survival. This retrospective cohort study
      underscores the importance of patient comorbidity in our management algorithm,
      and these data should prompt subsequent guidelines to factor in such comorbidity.

PMID- 28766562
TI  - Continuing Medical Education: August 2017: The Association between Distal
      Findings and Proximal Colorectal Neoplasia: A Systematic Review and Meta
      Analysis.

PMID- 28766563
TI  - Editorial: The Effect of Bias on Estimation of Improved Survival After Diagnosis
      of Barrett's Esophagus.
AB  - Adjustments for lead and length time bias has been used when examining apparent
      survival advantages from screening procedures. However, these estimates depend on
      several assumptions and are modeled from malignancies that are fairly common and
      large cohorts are available. In smaller retrospective cohorts, adjustments
      themselves may be based on estimates that may not be biological nor statistically
      accurate, which can lead to divergent results as has been found in several recent
      studies of screening in Barrett's esophagus. Only a prospective randomized
      controlled trial can really determine the benefit though this may not feasible.

PMID- 28766564
TI  - Pancreatic Panniculitis.

PMID- 28766567
TI  - Submucosal Tunneling and Endoscopic Resection of a Huge Gastric Lipoma.

PMID- 28766566
TI  - Editorial: Benefit of Direct-Acting Antiviral Therapy For Cryoglobulinemia due to
      Hepatitis C Infection.
AB  - Extrahepatic consequences of hepatitis C infection are increasingly recognized as
      a source of additional morbidity distinct from the consequences of liver disease.
      Among the best characterized of these is mixed cryoglobulinemia, which can lead
      to a variety of disorders, including vasculitis and glomerulonephritis. In
      general, the results of antiviral therapy in the interferon era had been
      disappointing, but now with new all-oral regimens response rates are
      substantially better. However, even with successful clearance of the virus
      symptomatic response can lag.

PMID- 28766568
TI  - First Case of Radiation-Induced Diffuse Hemorrhagic Gastritis Successfully
      Treated with Intravenous Bevazicumab.

PMID- 28766569
TI  - Ectopic Hepatocellular Carcinoma within a Choledochal Cyst Diagnosed Using Single
      Operator Digital Cholangioscopy.

PMID- 28766570
TI  - Acute Fatty Liver of Pregnancy-Differential Diagnosis.

PMID- 28766571
TI  - Continuing Medical Education Questions: August 2017: The Association between
      Distal Findings and Proximal Colorectal Neoplasia: A Systematic Review and Meta
      Analysis.

PMID- 28766572
TI  - Esophageal Stents in Aortoesophageal Fistulas-Anecdotal Experiences or New
      Armamentarium?

PMID- 28766573
TI  - The Importance of Time and Bedside Skills.

PMID- 28766574
TI  - A Cystic Teratoma Mimicking a Hydatid Cyst.

PMID- 28766575
TI  - Response to Dr Giannini et al.

PMID- 28766576
TI  - A Nodule, is a Nodule, is a Nodule: May Alpha-Fetoprotein Make the Difference?

PMID- 28766577
TI  - Dry Gangrene Secondary to Severe Acute Pancreatitis.

PMID- 28766578
TI  - Response to Morton.

PMID- 28766579
TI  - Central Anticholinergic Syndrome after Propofol Sedation for Upper GI Endoscopy.

PMID- 28766580
TI  - A Rapidly Enlarging Mullerian-Derived Hepatic Adenomyoma Clinically Mimicking
      Hepatic Adenoma in a Pregnant Woman.

PMID- 28766581
TI  - Continuing Medical Education Questions: August 2017.

PMID- 28766582
TI  - Continuing Medical Education: August 2017: Bloating and Abdominal Distension: Old
      Misconceptions and Current Knowledge.

PMID- 28766583
TI  - Niacin-Associated Acute Hepatotoxicity Leading to Emergency Liver
      Transplantation.

PMID- 28766585
TI  - The relevance of periprocedural troponin rise: the never ending story!

PMID- 28766586
TI  - Concerning the article by Louveau et al "Clinical value of early detection of
      circulating tumour DNA BRAFV600mut in patients with metastatic melanoma treated
      with a BRAF inhibitor".

PMID- 28766584
TI  - Transcriptional Variation of Diverse Enteropathogenic Escherichia coli Isolates
      under Virulence-Inducing Conditions.
AB  - Enteropathogenic Escherichia coli (EPEC) bacteria are a diverse group of
      pathogens that cause moderate to severe diarrhea in young children in developing
      countries. EPEC isolates can be further subclassified as typical EPEC (tEPEC)
      isolates that contain the bundle-forming pilus (BFP) or as atypical EPEC (aEPEC)
      isolates that do not contain BFP. Comparative genomics studies have recently
      highlighted the considerable genomic diversity among EPEC isolates. In the
      current study, we used RNA sequencing (RNA-Seq) to characterize the global
      transcriptomes of eight tEPEC isolates representing the identified genomic
      diversity, as well as one aEPEC isolate. The global transcriptomes were
      determined for the EPEC isolates under conditions of laboratory growth that are
      known to induce expression of virulence-associated genes. The findings
      demonstrate that unique genes of EPEC isolates from diverse phylogenomic lineages
      contribute to variation in their global transcriptomes. There were also
      phylogroup-specific differences in the global transcriptomes, including genes
      involved in iron acquisition, which had significant differential expression in
      the EPEC isolates belonging to phylogroup B2. Also, three EPEC isolates from the
      same phylogenomic lineage (EPEC8) had greater levels of similarity in their
      genomic content and exhibited greater similarities in their global transcriptomes
      than EPEC from other lineages; however, even among closely related isolates there
      were isolate-specific differences among their transcriptomes. These findings
      highlight the transcriptional variability that correlates with the previously
      unappreciated genomic diversity of EPEC. IMPORTANCE Recent studies have
      demonstrated that there is considerable genomic diversity among EPEC isolates;
      however, it is unknown if this genomic diversity leads to differences in their
      global transcription. This study used RNA-Seq to compare the global
      transcriptomes of EPEC isolates from diverse phylogenomic lineages. We
      demonstrate that there are lineage- and isolate-specific differences in the
      transcriptomes of genomically diverse EPEC isolates during growth under in vitro
      virulence-inducing conditions. This study addressed biological variation among
      isolates of a single pathovar in an effort to demonstrate that while each of
      these isolates is considered an EPEC isolate, there is significant
      transcriptional diversity among members of this pathovar. Future studies should
      consider whether this previously undescribed transcriptional variation may play a
      significant role in isolate-specific variability of EPEC clinical presentations.

PMID- 28766587
TI  - An atypical interaction explains the high-affinity of a non-hydrolyzable S-linked
      1,6-alpha-mannanase inhibitor.
AB  - The non-hydrolyzable S-linked azasugars, 1,6-alpha-mannosylthio- and 1,6-alpha
      mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity
      to a family 76 endo-1,6-alpha-mannanase from Bacillus circulans. X-ray
      crystallography showed an atypical interaction of the isofagomine nitrogen with
      the catalytic acid/base. Molecular dynamics simulations reveal that the atypical
      binding results from sulfur perturbing the most stable form away from the
      nucleophile interaction preferred for the O-linked congener.

PMID- 28766588
TI  - Redox-controlled self-inclusion of a lasso-type pseudo[1]rotaxane.
AB  - The self-inclusion behavior of a tetrathiafulvalene-containing lasso-type
      pseudo[1]rotaxane can be reversibly switched between threaded and non-threaded
      states by redox-stimuli. The switching mechanism was investigated by cyclic
      voltammetry in solution and monitored by ion mobility mass spectrometry in the
      gas phase.

PMID- 28766589
TI  - Facile preparation of pyrimidinediones and thioacrylamides via reductive
      functionalization of amides.
AB  - The development of an efficient protocol for the reductive functionalization of
      amides into pyrimidinediones and amino-substituted thioacrylamides is presented.
      Enamines are generated in a highly chemoselective amide hydrosilylation reaction
      catalyzed by molybdenum hexacarbonyl in combination with 1,1,3,3
      tetramethyldisiloxane. The direct addition of either isocyanate or isothiocyanate
      generates the corresponding pyrimidinediones and 3-aminothioacrylamides in high
      yields.

PMID- 28766590
TI  - Structure-guided synthesis of a protein-based fluorescent sensor for alkyl
      halides.
AB  - Alkyl halides are potentially mutagenic carcinogens. However, no efficient
      fluorescent sensor for alkyl halide detection in human-derived samples has been
      developed to date. Herein, we report a new protein-based fluorescent sensor for
      alkyl halides. Analysis of the HaloTag holo-crystal structure with its covalently
      attached ligand revealed an unexpected cavity, allowing for the design of a new
      fluorogenic ligand. This ligand showed the highest fluorescence response (300
      fold) and fastest binding kinetics (t1/2 < 150 s) to a HaloTag mutant (M175P)
      protein. This protein-based sensor system was effectively used to detect alkyl
      halides in human serum and monitor real-time protein alkylation.

PMID- 28766591
TI  - Reversible photoreduction of Cu(ii)-coumarin metal-organic polyhedra.
AB  - We report a new approach for photoinduced reduction of Cu2+ that will enrich the
      structural diversity of coordination complexes and be a valuable contributor to
      the development of Cu+/Cu0-based catalysts. To realize controlled Cu2+ reduction,
      coumarin as a triplet quencher of excited benzophenone was tethered to Cu(ii)
      metal-organic polyhedra (MOPs). The photoinduced catalytic activity of the
      coumarin-MOPs was also examined in a Cu(i)-catalyzed azide-alkyne cycloaddition
      (CuAAC).

PMID- 28766592
TI  - Organic dispersions of graphene oxide with arbitrary concentrations and improved
      chemical stability.
AB  - We report a simple method that can dissolve graphene oxide (GO) in pure organic
      solvents (e.g., propylene carbonate) as readily as in pure water to form stable
      dispersions of single layer GO sheets. The GO sheets dispersed in propylene
      carbonate exhibited much better structural stability than those in water.

PMID- 28766593
TI  - Triplet state CPL active helicene-dithiolene platinum bipyridine complexes.
AB  - Chiral metal dithiolene complexes represent a family of chiral precursors, which
      can give rise to molecular materials with properties resulting from the interplay
      of chirality with conductivity, magnetism, and photophysics. We describe herein
      the first examples of chiral metal diimine dithiolene complexes, by the use of a
      platinum(ii) centre coordinated by 2,2'-bipyridine and helicene-dithiolene
      ligands. The straightforward synthesis of racemic and enantiopure complexes
      allows the preparation of luminescent Pt(bipy) [4] and [6]helicene compounds for
      which the solid-state structure was determined as well. TD-DFT calculations
      support the assignment of the low-energy bands observed in the UV-vis absorption
      spectra as mixed metal-ligand-to-ligand charge transfer transitions and confirm
      that the emission band results from the T1 excited state. Interestingly, the
      enantiopure [6]helicene complexes show CPL activity at room temperature in
      acetonitrile solutions with an anisotropy factor of 3 * 10-4.

PMID- 28766594
TI  - Liquid-immune structural colors with angle-independence inspired from hollow
      melanosomes.
AB  - In this work, hollow polydopamine (PDA) amorphous colloidal structures with
      liquid-immune and angle-independent structural colors have been successfully
      fabricated. Owing to the high refractive index contrast derived from hollow PDA,
      and its light-absorbing nature, the as-prepared colloidal materials demonstrate
      brilliant structural colors even in liquid environments.

PMID- 28766596
TI  - Intracavity folding of a perylene dye affords a high-affinity complex with
      cucurbit[8]uril.
AB  - A fluorescent perylene dye with two aromatic units was designed for binding to
      cucurbit[8]uril. The binding affinity of the complexes increased about 3 orders
      of magnitude compared to the dye without a secondary aromatic unit. The high
      affinity allows the complexes to act as fluorescent probes for detection of
      strong binding guests with nanomolar sensitivity.

PMID- 28766595
TI  - Design, synthesis, and evaluation of heparan sulfate mimicking glycopolymers for
      inhibiting heparanase activity.
AB  - Heparanase is an enzyme which cleaves heparan sulfate (HS) polysaccharides of the
      extracellular matrix. It is a regulator of tumor behavior, plays a key role in
      kidney related diseases and autoimmune diabetes. We report herein the use of
      computational studies to extract the natural HS-heparanase interactions as a
      template for the design of HS mimicking glycopolymers. Upon evaluation, a
      glycopolymer with 12 repeating units was determined to be the most potent
      inhibitor and to have tight-binding characteristics. This glycopolymer also lacks
      anticoagulant activity.

PMID- 28766597
TI  - Desorption dynamics of CO2 from formate decomposition on Cu(111).
AB  - We performed ab initio molecular dynamics analysis of formate decomposition to
      CO2 and H on a Cu(111) surface using van der Waals density functionals. Our
      analysis shows that the desorbed CO2 has approximately twice larger bending
      vibrational energy than the translational, rotational, and stretching vibrational
      energies. Since formate synthesis, the reverse reaction of formate decomposition,
      has been suggested experimentally to occur via the Eley-Rideal mechanism, our
      results indicate that the formate synthesis can be enhanced if the bending
      vibrational mode of CO2 is excited rather than the translational and/or
      stretching vibrational modes. Detailed information on the energy distribution of
      desorbed CO2 as a formate decomposition product may provide new insights for
      improving the catalytic activity of formate synthesis.

PMID- 28766598
TI  - Dissecting the chloride-nitrate anion transport assay.
AB  - A systematic study of chloride vs. nitrate selectivity across six anion
      transporters has revealed a good correlation between the selectivities of their
      anion binding and membrane transport properties. This work reveals the
      limitations of the chloride-nitrate exchange assay and shows how new approaches
      can be used to measure anion uniport.

PMID- 28766599
TI  - Flexible imidazolium macrocycles: building blocks for anion-induced self
      assembly.
AB  - This feature article summarises recent contributions of the authors in the area
      of anion-induced supramolecular self-assembly. It is based on the chemistry of a
      set of tetracationic imidazolium macrocycles, specifically the so-called 'Texas
      sized' molecular box, cyclo[2](2,6-di(1H-imidazol-1-yl)pyridine)[2](1,4
      dimethylenebenzene) (14+), and its congeners, cyclo[2](2,6-di(1H-imidazol-1
      yl)pyridine)[2](1,2-dimethylenebenzene) (24+), cyclo[2](2,6-di(1H-imidazol-1
      yl)pyridine)[2](1,3-dimethylenebenzene) (34+), and cyclo[2](2,6-di(1H-imidazol-1
      yl)pyridine)[2](2,6-dimethylenepyridine) (44+). These systems collectively have
      been demonstrated as being versatile building blocks that interact with organic
      carboxylate or sulfonate anions, as well as substrates (e.g., neutral molecules
      or metal cations). Most work to date has been carried out with 14+, a system that
      has been found to support the construction of a number of stimuli responsive self
      assembled ensembles. This macrocycle and others of the 'Texas-sized' box family
      also show the potential to react as carbene precursors and to undergo post
      synthetic modification (PSM) to produce new functional macrocycles, such as trans
      and cis-cyclo[2]((Z)-N-(2-((6-(1H-imidazol-1-yl)pyridin-2
      yl)amino)vinyl)formamide)[2](1,4-bismethylbenzene) (52+ and 62+, respectively).
      On the basis of the work reviewed in this Feature article, we propose that the
      imidazolium macrocycles 14+-44+ can be considered as useful tools for the
      construction of ensembles with environmentally responsive features, including
      control over self-assembly and an ability to undergo precursor-specific PSM.

PMID- 28766600
TI  - Moisture resistant and biofriendly CD-MOF nanoparticles obtained via cholesterol
      shielding.
AB  - A facile and one step-method was developed to enhance the water stability of CD
      MOF nanoparticles through surface modification with cholesterol. CD-MOFs were
      able to maintain their cubic crystalline structures even after 24 h of
      incubation, well tolerated in vivo and could increase up to 4 times the blood
      half-life of DOX.

PMID- 28766601
TI  - Theoretical tuning of the singlet-triplet energy gap to achieve efficient long
      wavelength thermally activated delayed fluorescence emitters: the impact of
      substituents.
AB  - Great progress has been made in developing highly efficient thermally activated
      delayed fluorescent (TADF) materials. However, developing highly efficient long
      wavelength TADF emitters is still a challenge because a small energy gap
      (DeltaEST) between the lowest singlet (S1) and triplet excited states (T1) and a
      relatively high fluorescence rate are difficult to achieve simultaneously in one
      molecule. Here, eleven donor-acceptor (D-A) type molecules using N3,N3,N6,N6
      tetraphenyl-9H-carbazole-3,6-diamine (named DAC-II) as the electron donor and the
      2-phenyl-quinoxaline-based electron acceptor are designed via introducing
      different electron-donating and electron-withdrawing groups into the acceptor and
      changing the connection position between the donor (D) and the acceptor (A).
      Quantum chemical calculations indicated that introducing the electron-donating
      groups (-OCH3, -CH3) into the phenyl ring of the acceptor, molecules 2 and 3,
      cannot change the emission property of molecule 1, thus molecules 2 and 3 could
      also be used as green TADF emitters like molecule 1. Introducing an electron
      withdrawing unit (-CF3) into molecule 1, molecule 4, reduces the DeltaEST value
      to 0.10 eV, while the radiative decay rate (kVE) is also reduced correspondingly.
      Changing the connection position between D and A, molecules 5 to 8, cannot reduce
      the DeltaEST value and lowers the kVE value compared with molecules 1 to 4.
      However, introducing electron-withdrawing groups (-2F, -4F and -CN) into the
      quinoxaline moiety, molecules 9 to 11, contributes to both small DeltaEST and
      large kVE for the emission process. The values of DeltaEST of molecules 9 to 11
      are in the range of 0.21 to 0.30 eV, and the maximum emission wavelengths of
      molecules 10 and 11 are 576 and 590 nm, respectively, which are promising to be
      used as efficient yellow and orange TADF emitters in organic light-emitting
      diodes.

PMID- 28766602
TI  - Understanding water structure from Raman spectra of isotopic substitution H2O/D2O
      up to 573 K.
AB  - The OH/OD stretch band on Raman spectra of water is complex, and understanding
      the spectral features based on water structure needs further study. This study
      investigates Raman spectra of isotopic substitution (IS) of water (with volume
      ratio VH2O/VD2O of 0/1, 1/4, 1/1, 4/1 and 1/0) at temperatures from 303 to 573 K.
      The data show that the OH and OD stretch band profiles are similar in their
      dependences on temperature and IS ratio. IS reduces the band widths at low
      temperatures but the reducing effect diminishes above ~450 K, due to the largely
      enhanced intensity of the high-frequency shoulder (~3650 cm-1/2690 cm-1), which
      turns into the main peak for the OH (or OD) stretch bands when VH2O/VD2O (or
      VD2O/VH2O) reaches 1/4 at temperatures over ~510 K. These spectral features
      strongly indicate a multi-structure model stating that water has various local
      hydrogen bonding (HB) environments. Intermolecular vibrational couplings are
      important in determining the band width, while intramolecular vibrational
      couplings are not recommended for interpreting the OH/OD stretch band. Five
      dominant HB configurations are identified in water: two types of tetrahedral,
      single donor (SD) HB configuration, single hydrogen-bonded water (SHW), and free
      water (FW) without any hydrogen bonds, which are represented by five sub-bands.
      It is estimated that most (>50%) of the water molecules are in highly asymmetric
      HB environments (SD and SHW). The increase of temperature breaks HB structure and
      IS further promotes structure transition from tetrahedral to SD, SHW and FW.
      Then, number of hydrogen bonds in water are greatly reduced by temperature and
      IS.

PMID- 28766603
TI  - Characterization of secondary phosphine oxide ligands on the surface of iridium
      nanoparticles.
AB  - The synthesis of iridium nanoparticles (IrNPs) ligated by various secondary
      phosphine oxides (SPOs) is described. This highly reproducible and simple method
      via H2 reduction produces well dispersed, small nanoparticles (NPs), which were
      characterized by the state-of-the-art techniques, such as TEM, HRTEM, WAXS and
      ATR FT-IR spectroscopy. In particular, multinuclear solid state MAS-NMR
      spectroscopy with and without cross polarization (CP) enabled us to investigate
      the different binding modes adopted by the ligand at the nanoparticle surface,
      suggesting the presence of three possible types of coordination: as a purely
      anionic ligand Ir-P(O)R2, as a neutral acid R2P-O-H and as a monoanionic
      bidentate H-bonded dimer R2P-O-HO[double bond, length as m-dash]PR2.
      Specifically, the higher basicity of the dicyclohexyl system leads to the
      formation of IrNPs in which the bidentate binding mode is most abundant. Such
      cyclohexyl groups are bent towards the edges, as is suggested by the study of
      13CO coordination on the NP surface. This study also showed that the number of
      surface sites on faces available for bridging CO molecules is higher than the
      number of sites for terminal CO species on edges and apices, which is unexpected
      taking into account the small size of the nanoparticles. In addition, the IrNPs
      present a high chemoselectivity in the hydrogenation of cinnamaldehyde to the
      unsaturated alcohol.

PMID- 28766604
TI  - Stepwise deprotonation of sumanene: electronic structures, energetics and
      aromaticity alterations.
AB  - The first comprehensive theoretical investigation of structural, energetic, and
      electronic changes in a sumanene skeleton, C21H12, upon a step-wise deprotonation
      process is performed. This study is complemented by a detailed consideration of
      aromaticity in target bowl-shaped systems, including neutral sumanene and its
      three deprotonated anions, namely C21H111-, C21H102-, and C21H93-. In order to
      obtain the most reliable and method-independent characteristics, a set of
      aromatic descriptors of different nature has been applied. It included structure
      based HOMA, topological descriptors PDI and FLU, as well as magnetic NICS and
      ACID. The calculation results reveal that the neutral sumanene can be best
      described as mechanically bent triphenylene, in which pi-conjugation is mostly
      localized over three peripheral 6-membered rings. Sequential deprotonation
      changed the system from the localized mono-anionic to semi-localized di-anionic,
      and eventually to the fully delocalized tri-anionic sumanenyl species. Structural
      changes, namely, bond equalization upon the deprotonation process, are in
      excellent agreement with alterations observed in electronic structures and
      aromaticity. Deprotonation results in a significant reduction of the barrier for
      a bowl-to-bowl transition only in the tri-anionic sumanenyl system, whereas the
      first and the second deprotonation steps show no notable effect. This clearly
      indicates that only complete aromatization of the sumanene core in C21H93- leads
      to a substantial increase of bowl flexibility.

PMID- 28766605
TI  - An investigation of the in-plane chemically ordered atomic laminates
      (Mo2/3Sc1/3)2AlC and (Mo2/3Y1/3)2AlC from first principles.
AB  - We have calculated electronic, vibrational, and elastic properties of
      (Mo2/3Sc1/3)2AlC and (Mo2/3Y1/3)2AlC, two recently discovered nanolaminated
      materials in the family of so-called i-MAX phases. A comparison is made to the
      properties of the related hypothetical MAX phases Sc2AlC, Y2AlC, and Mo2AlC. From
      an analysis of the electronic band structures and projected crystal orbital
      Hamilton populations (pCOHP), we show that the i-MAX phases have more isotropic
      band structures than the MAX phases, but that their bonding characteristics are
      very similar, despite belonging to different space groups. However, the similar
      bonding notwithstanding, qualitative as well as significant quantitative
      differences are seen in the phonon density of states (PDOS). We also compare the
      Voigt-Reuss-Hill (VRH) bulk, shear, and Young's moduli. For (Mo2/3Sc1/3)2AlC,
      BVRH = 132 GPa, GVRH = 89 GPa, and EVRH = 218 GPa, all of which are higher values
      than for Sc2AlC, but lower than for Mo2AlC. For (Mo2/3Y1/3)2AlC, BVRH = 117 GPa,
      GVRH = 85 GPa, and EVRH = 205 GPa, which are higher than for Y2AlC, but lower
      than for Mo2AlC.

PMID- 28766606
TI  - Redox cycling of iron by carbon dot enhanced chemiluminescence: mechanism of
      electron-hole induction in carbon dot.
AB  - The chemiluminescence (CL) of the Fenton system with nitrogen doped carbon dots
      (N-CDs) was significantly enhanced. The introduction of N-CDs improved the
      utilization of H2O2 and drastically enhanced the generation of OH, which resulted
      in enhanced CL emission of the Fenton system through energy and electron transfer
      processes. The oxidation of N-CDs by OH led to rapid incorporation of oxygen into
      N-CDs. The mechanism relied on the production of *OH radicals through the Fenton
      reaction and clearly indicated the important role of peroxide-induced redox
      cycling of Fe2+ <=> Fe3+ in the presence of N-CDs. The CL intensity of the system
      containing Fe2+ was higher than that containing Fe3+ because the rate of the Fe3+
      reaction was much slower than that of the Fe2+ reaction. The CL signal remained
      constant after some time due to redox cycling, which established equilibrium,
      irrespective of the form of iron. This study provides a feasible approach to
      greatly enhance the weak CL of the Fenton system with the introduction of
      environmentally friendly N-CDs, and initiates an inspiring research in the domain
      of catalysis, CL and the mechanism of the Fenton system, which will be helpful in
      various applied research areas.

PMID- 28766607
TI  - A chemometric approach for determining the reaction quantum yields in consecutive
      photochemical processes.
AB  - A chemometric procedure to deal with spectroscopically monitored processes
      involving photochemical steps is fully described. The methodology makes it
      possible to work with reactions that involve several components with unknown (and
      eventually overlapping) spectra and provides a tool for the simultaneous
      determination of both the quantum yields of the reaction and the spectra of all
      the species present in a multi-step photochemical process. As a benchmark, we
      apply these ideas to extract the quantum yields of photodetachment of coordinated
      ligands employing data recorded over the course of the decomposition of
      [Ru(tpm)(bpy)(CH3CN)]2+ and cis-[Ru(bpy)2(CH3CN)2]2+ under stationary photolysis
      conditions. The approach is fast and robust and it is easily implemented in
      scientific programming languages.

PMID- 28766610
TI  - Optical properties and magnetic flux-induced electronic band tuning of a T
      graphene sheet and nanoribbon.
AB  - Tetragonal graphene (T-graphene) is a theoretically proposed dynamically stable,
      metallic allotrope of graphene. In this theoretical investigation, a tight
      binding (TB) model is used to unravel the metal to semiconductor transition of
      this 2D sheet under the influence of an external magnetic flux. In addition, the
      environment under which the sheet exposes an appreciable direct band gap of 1.41
      +/- 0.01 eV is examined. Similarly, the electronic band structure of the
      narrowest armchair T-graphene nanoribbon (NATGNR) also gets modified with
      different combinations of magnetic fluxes through the elementary rings. The band
      tuning parameters are critically identified for both systems. It is observed that
      the induced band gaps vary remarkably with the tuning parameters. We have also
      introduced an exact analytical approach to address the band structure of the
      NATGNR in the absence of any magnetic flux. Finally, the optical properties of
      the sheet and NATGNR are also critically analysed for both parallel and
      perpendicular polarizations with the help of density functional theory (DFT). Our
      study predicts that this material and its nanoribbons can be used in
      optoelectronic devices.

PMID- 28766611
TI  - Ferrocene and ferrocenium inclusion compounds with cucurbiturils: a study of
      metal atom dynamics probed by Mossbauer spectroscopy.
AB  - Temperature-dependent 57Fe Mossbauer effect (ME) spectroscopic studies were
      carried out on ferrocene (Fc), 1,1'-dimethylferrocene (1,1'(CH3)2Fc) and
      ferrocenium hexafluorophosphate (FcPF6) guest species in cucurbit[n]uril (n = 7,
      8) inclusion complexes. The solid inclusion complexes were isolated by freeze
      drying of dilute aqueous solutions and/or microwave-assisted precipitation from
      concentrated mixtures. The presence of genuine 1 : 1 (host : guest) inclusion
      complexes in the isolated solids was supported by liquid-state 1H and solid-state
      13C{1H} MAS NMR, elemental and thermogravimetric analyses, powder X-ray
      diffraction, FTIR spectroscopy, and diffuse reflectance UV-Vis spectroscopy. The
      ME spectra of the complexes CB7.Fc and CB7.1,1'(CH3)2Fc consist of well-resolved
      doublets with hyperfine parameters (isomer shift and quadrupole splitting at 90
      K) and temperature-dependent recoil-free fraction data that are very similar to
      those for the neat parent compounds, Fc and 1,1'(CH3)2Fc, suggesting that the
      organometallic guest molecules do not interact significantly with the host
      environment over the experimental temperature range. The ME spectra for CB7.FcPF6
      and CB8.FcPF6 consist of a major broad line resonance attributed to a
      paramagnetic FeIII site. From the temperature-dependence of the recoil-free
      fraction it is evident that the charged guest species in these systems interact
      with the host environment significantly more strongly than was observed in the
      case of the neutral guest species, Fc and 1,1'(CH3)2Fc. Moreover, the ME data
      indicate that the vibrational amplitude of the ferrocenium guest molecule is
      significantly larger in the CB8 host molecule than in the CB7 homologue, as
      expected on the basis of the different cavity sizes.

PMID- 28766612
TI  - Reply to comment on "Brownian diffusion of a particle at an air/liquid interface:
      elastic (not viscous) response of the surface".

PMID- 28766613
TI  - A novel highly selective ligand for separation of actinides and lanthanides in
      the nuclear fuel cycle. Experimental verification of the theoretical prediction.
AB  - We have predicted earlier by DFT simulation that tridentate O,N,O-donor cyclic
      dilactams (B) belonging to the family of pyridine-2,6-dicarboxamides are much
      more selective and efficient extractants for the separation of lanthanides and
      actinides than open-structure pyridine-2,6-dicarboxamides due to the higher
      degree of "ligand preorganization". In the present work, three new ligands of
      type (B) were synthesized. Extraction experiments showed that, in line with the
      data from DFT simulation, these ligands have 5-6-fold higher selectivity for the
      separation of an Am3+/Eu3+ pair and provide distribution coefficients D which are
      by three orders of magnitude higher than those for the related parent ligands
      with an open structure. Determination of the solvate numbers (SNs) for Eu3+ and
      Am3+ cations by slope analysis has shown that the stoichiometry of complexes, in
      the form of which these ions pass from the aqueous into the organic phase,
      depends to a considerable extent on the polarity of the organic solvent. Strongly
      polar solvents (epsilon > 20) extract these cations mainly in the form of 1 : 1
      complexes LM(NO3)3 having according to the DFT simulation the largest dipole
      moments (MU = 18.6-19.7 D). The solvents of low polarity (epsilon <= 10) extract
      these cations mainly in the form of less polar 2 : 1 complexes L2M(NO3)3 (MU ~
      1.6 D). For solvents of intermediate polarity fractional values of solvate
      numbers were obtained which indicates the coexistence of complexes LM(NO3)3 and
      L2M(NO3)3 in the organic phase.

PMID- 28766614
TI  - Rotationally resolved electronic spectroscopy of the rotamers of 1,3
      dimethoxybenzene.
AB  - Conformational assignments in molecular beam experiments are often based on
      relative energies, although there are many other relevant parameters, such as
      conformer-dependent oscillator strengths, Franck-Condon factors, quantum yields
      and vibronic couplings. In the present contribution, we investigate the
      conformational landscape of 1,3-dimethoxybenzene using a combination of
      rotationally resolved electronic spectroscopy and high level ab initio
      calculations. The electronic origin of one of the three possible planar rotamers
      (rotamer (0,180) with both substituents pointing at each other) has not been
      found. Based on the calculated potential energy surface of 1,3-dimethoxybenzene
      in the electronic ground and lowest excited state, we show that this can be
      explained by a distorted non-planar geometry of rotamer (0,180) in the S1 state.

PMID- 28766615
TI  - Rare-earth doped fluoride phosphate glasses: structural foundations of their
      luminescence properties.
AB  - We report a detailed structural investigation of a series of fluoride-phosphate
      glasses with different phosphate/fluoride ratios in the system xSr(PO3)2-(100 -
      x)[AlF3-CaF2-SrF2-MgF2] with x = 5, 10, 20, 40. Raman and multinuclear solid NMR
      spectroscopies confirm that the polyphosphate network structure is successively
      transformed to a structure dominated by Al-O-P linkages with increasing AlF3
      content. Average numbers of Al-O-P linkages have been quantified by 27Al/31P NMR
      double-resonance techniques. The majority of the fluoride species are found in an
      alkaline earth metal/aluminum rich environment. The local environments for rare
      earth ions have been characterized by EPR spectroscopy of Yb3+ ion spin probes
      and by photoluminescence experiments on Eu3+ dopant ions, including the 5D0 ->
      7F2 and 5D0 -> 7F1 transition intensity ratio, the normalized phonon sideband
      intensities in the excitation spectra, and the lifetime of the 5D0 excited state.
      The results indicate clear correlations between these parameters as a function of
      composition, and confirm that even at the highest fluoride levels, there is still
      some residual rare-earth phosphate coordination.

PMID- 28766616
TI  - Investigation of the dispersion behavior of fluorinated MWCNTs in various
      solvents.
AB  - The investigation of the dispersion behavior of fluorinated MWCNTs (F-MWCNTs) is
      very important to understand their structure and take full advantage of their
      good properties. In this present paper, the dispersion behavior of F-MWCNTs with
      a low content and a high content of fluorine (denoted as lF-MWCNTs and hF-MWCNTs)
      was explored in 18 kinds of common solvents. The surface of hF-MWCNTs is
      considered to be a heterostructure consisting of fluorinated regions and aromatic
      regions, while lF-MWCNTs are inclined to be a homogeneous structure on the basis
      of their dispersion behavior. According to dispersion theory based on surface
      energy and Hansen solubility parameters (HSPs), it was indicated that the
      corresponding preferable solvents are different for different regions. As a
      result, good solvents of hF-MWCNTs are distributed in a quite wide scope while lF
      MWCNTs can be dispersed only in a significantly narrow range of solvents. The
      HSPs of lF-MWCNTs and hF-MWCNTs are determined to be deltaD = 17.6 MPa1/2, deltaP
      = 11.8 MPa1/2, deltaH = 8.8 MPa1/2 and deltaD = 16.9 MPa1/2, deltaP = 9.3 MPa1/2,
      deltaH = 13.5 MPa1/2, respectively. As a result, mixed solvents of acetone and
      water were carefully tuned to be compatible with hF-MWCNTs. The dispersion
      behaviors of lF-MWCNTs and hF-MWCNTs in epoxy were also predicted according to
      HSPs. It was found that hF-MWCNTs maintain a stable dispersion in epoxy due to
      their heterogeneous structure at elevated temperatures.

PMID- 28766618
TI  - Synthesis of divalent ytterbium terphenylamide and catalytic application for
      regioselective hydrosilylation of alkenes.
AB  - The dimeric heteroleptic ytterbium amido complex [(2,6-(3,5
      Me2C6H3)2C6H3NH)Yb(N(SiMe3)2)]2 (1) has been prepared and characterized. This
      divalent terphenylamido complex enabled highly regioselective hydrosilylation of
      various terminal alkenes with very low catalyst loadings. The reaction of 1 with
      phenylsilane at high temperature led to the dehydrogenative coupling of silane
      with a terphenylamide ligand and redistributions of amide ligands via a
      hypervalent silane intermediate, which has been spectroscopically characterized.

PMID- 28766617
TI  - Hydrothermal assembly, structures, topologies, luminescence, and magnetism of a
      novel series of coordination polymers driven by a trifunctional nicotinic acid
      building block.
AB  - In this work, a trifunctional N,O-building block, 5-(4-carboxyphenoxy)nicotinic
      acid (H2cpna), that combines three distinct types of functional groups (COOH, N
      pyridyl, and O-ether) was used for the hydrothermal assembly of thirteen new
      coordination compounds: [Co(MU3-Hcpna)2]n (1), [Mn(MU4-cpna)(H2O)]n (2), [Mn(MU4
      cpna)(H2O)2]n (3), [Mn(MU-cpna)(2,2'-bipy)(H2O)2]n (4), {[Ni(MU3-cpna)(2,2'
      bipy)(H2O)]2.H2O}n (5), {[Cd(MU3-cpna)(2,2'-bipy)].2H2O}n (6), [Zn2(MU
      cpna)2(2,2'-bipy)2] (7), [Cu(MU-cpna)(2,2'-bipy)(H2O)]n (8), {[Mn(MU
      cpna)(phen)2].6H2O}n (9), {[Ni(MU3-cpna)(phen)(H2O)].H2O}n (10), [Zn2(MU
      cpna)2(phen)2] (11), {[Pb(MU3-cpna)(phen)].H2O}n (12), and [Ni(MU3-cpna)(4,4'
      bipy)0.5(H2O)]n (13). These products were synthesized from the corresponding
      metal(ii) chlorides, H2cpna, NaOH, and optional N-donor supporting ligands or
      templates {bis(4-pyridyl)amine (bpa), 2,2'-bipyridine (2,2'-bipy), 4,4'
      bipyridine (4,4'-bipy), or 1,10-phenanthroline (phen)}. Products 1-13 were
      characterized in the solid state by standard methods, including elemental and
      thermogravimetric analysis (TGA), IR spectroscopy, and powder (PXRD) and single
      crystal X-ray diffraction. The structures of 1-13 feature distinct structural
      types, namely the 3D metal-organic frameworks (MOFs 1-3), the 2D coordination
      polymers (5, 6, 10, 12, and 13), the 1D coordination polymers (4, 8, and 9), and
      the 0D discrete cyclic dimers (7 and 11). Such a wide structural diversity of 1
      13 is driven by various factors, including the type of the metal(ii) node, the
      deprotonation degree of H2cpna, and/or the type of supporting ligand or template.
      Notably, an addition of bpa can tune the structure of MOF 3 by the template
      effect. Topological classification of underlying metal-organic networks was
      performed, leading to several distinct topological nets: rtl (in 1), hxg-d-4-C2/m
      (in 2), sra (in 3), 2C1 (in 4, 8 and 9), fes (in 5, 10, and 12), hcb (in 6), and
      3,4L83 (in 13). The magnetic behavior of 1-5, 8-10, and 13 was studied and
      theoretically modeled, disclosing antiferromagnetic interactions. The
      luminescence behavior of 6, 7, 11, and 12 was also investigated.

PMID- 28766619
TI  - Magnetic circular dichroism and density functional theory studies of electronic
      structure and bonding in cobalt(ii)-N-heterocyclic carbene complexes.
AB  - The combination of simple cobalt salts and N-heterocyclic carbene (NHC) ligands
      has been highly effective in C-H functionalization, hydroarylation and cross
      coupling catalysis, though displaying a strong dependence on the identity of the
      NHC ligand. In addition, reactions effective with NHC ligands are often
      ineffective with phosphine ligands, further motivating the evaluation of the
      fundamental electronic structure and bonding differences in well-defined
      distorted tetrahedral Co(ii) complexes. Magnetic circular dichroism (MCD) studies
      indicate that Co(ii)-bisphosphines have larger ligand fields than Co(ii)-NHC
      complexes. Theoretical density functional theory (DFT) calculations were
      performed on an expanded set of L2CoCl2 complexes (L2 = NHC, bisphosphine and
      diamine) to study the electronic structure and relative ligation properties of
      NHCs compared to bisphosphine and diamine ligands. Mayer bond order and charge
      decomposition analyses indicate that NHC ligands are slightly stronger donor
      ligands than bisphosphines but also result in a weakening of Co-Cl bonds in a
      trans-like influence. From MCD and DFT studies, changing the NHC N-substituent
      has a larger effect on the ligand field of Co(ii)-NHC complexes than saturating
      the backbone. Overall, these studies provide detailed insight into the electronic
      structure and bonding effects in Co(ii) complexes with ligand types commonly
      explored in catalysis.

PMID- 28766621
TI  - Detailed phytochemical characterization and bioactive properties of Myrtus
      nivelii Batt & Trab.
AB  - The endemic Algerian myrtle, Myrtus nivelii Batt & Trab., was evaluated for its
      bioactive properties, such as antioxidant, anti-inflammatory, cytotoxic and
      antibacterial activities, and correlated with the individual phenolic compounds
      identified in its crude aqueous extract and subsequent organic fractions (ethyl
      acetate and butanol). Flavonols, such as myricetin, kaempferol and quercetin
      glycoside derivatives, were the major phenolic compounds found, along with the
      presence of ellagitannins. The ethyl acetate fraction contained the highest
      amount of phenolic compounds, followed by the butanol fraction and, finally, the
      crude aqueous extract. In general, all samples exhibited an excellent
      bioactivity, namely the ethyl acetate fraction that presented strong antioxidant
      activity, when compared to the standard trolox, strong cytotoxicity and
      antibacterial activity, especially against MRSA and MSSA. The present study
      revealed that the ethyl acetate fraction of M. nivelii could be used as a source
      of bioactive compounds in the food and pharmaceutical industries.

PMID- 28766622
TI  - Functional aqueous droplet networks.
AB  - Droplet interface bilayers (DIBs), comprising individual lipid bilayers between
      pairs of aqueous droplets in an oil, are proving to be a useful tool for studying
      membrane proteins. Recently, attention has turned to the elaboration of networks
      of aqueous droplets, connected through functionalized interface bilayers, with
      collective properties unachievable in droplet pairs. Small 2D collections of
      droplets have been formed into soft biodevices, which can act as electronic
      components, light-sensors and batteries. A substantial breakthrough has been the
      development of a droplet printer, which can create patterned 3D droplet networks
      of hundreds to thousands of connected droplets. The 3D networks can change shape,
      or carry electrical signals through defined pathways, or express proteins in
      response to patterned illumination. We envisage using functional 3D droplet
      networks as autonomous synthetic tissues or coupling them with cells to repair or
      enhance the properties of living tissues.

PMID- 28766623
TI  - The phosphinoboration of carbodiimides, isocyanates, isothiocyanates and CO2.
AB  - The transition metal-free addition of phosphinoboronate ester Ph2PBpin (pin = 1,2
      O2C2Me4) to heterocumulenes including carbodiimides, isocyanates, isothiocyanates
      and carbon dioxide has been investigated. The corresponding 1,2-addition products
      were readily prepared at room temperature without the need of a catalyst or added
      base. Addition of methanol to the compounds derived from addition of Ph2PBpin to
      carbodiimides, isocyanates, and isothiocyanates resulted in traditional
      hydrophosphination products. The methodology developed in this study provides a
      simple and elegant route for the generation of a wide range of functionalized
      phosphines. The phosphinoboronate ester Ph2PBpin also selectively and reversibly
      adds to CO2 at room temperature in a 1,2-manner.

PMID- 28766624
TI  - Generic nature of long-range repulsion mechanism on a bulk insulator?
AB  - Dynamic atomic force microscopy measurements are reported that provide evidence
      for the presence of long-range repulsion in molecular self-assembly on a bulk
      insulator surface. We present the structures formed from four different benzoic
      acid derivatives on the (10.4) cleavage plane of calcite kept in ultra-high
      vacuum. These molecules have in common that they self-assemble into molecular
      stripes when deposited onto the surface held at room temperature. For all
      molecules tested, a detailed analysis of the stripe-to-stripe distance
      distribution reveals a clear deviation from what would be expected for randomly
      placed, non-interacting stripes (i.e., geometric distribution). When excluding
      kinetic effects during growth, this result gives evidence for a long-range
      repulsion mechanism acting during the assembly of these stripes. The fact that
      this finding is robust against changes in the molecular structure indicates a
      generic nature of the observed mechanism, implying a ubiquitous origin such as
      electrostatic repulsion. Finally, we discuss parameters that might affect the
      unambiguous observation of this generic repulsion under specific experimental
      conditions.

PMID- 28766625
TI  - Self-assembly of a binodal metal-organic framework exhibiting a demi-regular
      lattice.
AB  - Designing metal-organic frameworks with new topologies is a long-standing quest
      because new topologies often accompany new properties and functions. Here we
      report that 1,3,5-tris[4-(pyridin-4-yl)phenyl]benzene molecules coordinate with
      Cu atoms to form a two-dimensional framework in which Cu adatoms form a nanometer
      scale demi-regular lattice. The lattice is articulated by perfectly arranged
      twofold and threefold pyridyl-Cu coordination motifs in a ratio of 1 : 6 and
      features local dodecagonal symmetry. This structure is thermodynamically robust
      and emerges solely when the molecular density is at a critical value. In
      comparison, we present three framework structures that consist of semi-regular
      and regular lattices of Cu atoms self-assembled out of 1,3,5-tris[4-(pyridin-4
      yl)phenyl]benzene and trispyridylbenzene molecules. Thus a family of regular,
      semi-regular and demi-regular lattices can be achieved by Cu-pyridyl
      coordination.

PMID- 28766626
TI  - Kinetic control in the temperature-dependent sequential growth of surface
      confined supramolecular copolymers.
AB  - We report the sequential growth of supramolecular copolymers on gold surfaces,
      using oppositely charged dendritic peptide amphiphiles. By including water
      solubilising thermoresponsive chains in the monomer design, we observed non
      linear effects in the temperature-dependent sequential growth. The step-wise
      copolymerisation process is characterised using temperature dependent SPR and QCM
      D measurements. At higher temperatures, dehydration of peripheral oligoethylene
      glycol chains supports copolymer growth due to more favourable comonomer
      interactions. Both monomers incorporate methionine amino acids but remarkably,
      desorption of the copolymers via competing sulphur gold interactions with the
      initial monomer layer is not observed. The surface-confined supramolecular
      copolymers remain kinetically trapped on the metal surface at near neutral pH and
      form viscoelastic films with a tuneable thickness.

PMID- 28766627
TI  - N-Heterocyclic carbene adducts of the heavier group 15 tribromides. Normal to
      abnormal isomerism and bromide ion abstraction.
AB  - The reactivity of the heavier group 15 tribromides, SbBr3 and BiBr3, towards 1,3
      bis(2,6-diisopropylphenyl)-imidazol-2-ylidene (IPr) is described. These reactions
      quantitatively afford Lewis acid-base adducts, (IPr)EBr3 (E = Sb 1; Bi 2), which
      readily react with AlBr3 yielding cationic species [(IPr)EBr2]+ (E = Sb 3; Bi 4).
      Under thermal treatment, the N-heterocyclic carbene ligands in 1 and 2 will
      readily isomerise to afford the abnormally-bonded (or mesoionic) complexes
      (aIPr)EBr3 (E = Sb 5; Bi 6). As with 1 and 2, bromide abstraction from such
      compounds readily affords the cationic complexes [(aIPr)EBr2]+ (E = Sb 7; Bi 8).
      Finally, in an effort to elucidate the isomerisation process which allows for the
      conversion of 1 and 2 to the abnormally bonded systems (compounds 5 and 6),
      compound 1 was reacted with a further equivalent of IPr to afford the cationic
      species [(aIPr)2SbBr2]+ (9). This strongly suggests that the normal to abnormal
      isomerisation of the N-heterocylic carbene ligands in compounds 1 and 2 is
      mediated by the presence of free IPr. Compound [9]Br can be used to access the
      dicationic species [(aIPr)2SbBr]2+ (10), which we have identified
      spectroscopically. Single crystal X-ray structures and spectroscopic data for all
      compounds are discussed.

PMID- 28766628
TI  - Liquid coordination complexes of Lewis acidic metal chlorides: Lewis acidity and
      insights into speciation.
AB  - Coordination complexes of Lewis acidic metal chlorides AlCl3, GaCl3, InCl3,
      SbCl3, SnCl4, SnCl2, ZnCl2 and TiCl4 with trioctylphosphine (P888) and
      trioctylphosphine oxide (P888O) were synthesised. All compounds formed liquid
      coordination complexes (LCCs) at ambient temperature, although decomposition via
      a redox mechanism was detected in some cases. The Lewis acidity of the metal
      chlorides (measured in 1,2-dichloroethane solutions) and the LCCs (measured neat)
      was quantified by using the Gutmann acceptor number (AN) approach. In general,
      LCCs were equally or more Lewis acidic than the corresponding metal chlorides.
      The AN values were compared with the catalytic activity of selected LCCs in a
      model Diels-Alder reaction. Insight into speciation of LCCs was gained using
      multinuclear NMR spectroscopy, revealing that most LCCs comprised charge-neutral
      complexes rather than ionic ones. The relationship between the speciation, Lewis
      acidity (AN scale) and catalytic activity is discussed in detail. This approach
      reveals several new, promising catalytic systems, such as P888O-InCl3, with Lewis
      acidity enhanced compared to chloroindate ionic liquids, and P888O-TiCl4, with
      hydrolytic stability enhanced with respect to neat TiCl4.

PMID- 28766629
TI  - Do halogen bonds dictate the packing preferences in solid solutions?
AB  - The isomeric compounds, 4-bromo-2-chloro benzoic acid (4Br) and 2-bromo-4
      chlorobenzoic acid (2Br), crystallize in entirely different space groups, P21/n
      and P1[combining macron] respectively. Both structures are stabilized by a strong
      O-HO hydrogen bonds generating a carboxylic acid dimer along with an unusual
      triangular halogen bonded motif in the former and a well-defined halogen bond in
      the latter. Charge density analysis establishes the nature of halogen bonds by
      bringing out significant changes in the packing features of the two structures as
      well as the quantification of the interaction energies involved in the formation
      of the motifs. Cocrystallization efforts lead to the formation of solid solutions
      of varied stoichiometric ratios among the two entirely different crystalline
      forms, a feature which is observed for the first time, and depends on the nature
      of the halogen bonds. Despite the significant variations in the charge density
      distribution in intermolecular space, the triangular motif, with two type II BrCl
      and ClBr and one type I BrBr contact in the structure of 4Br dictates the packing
      preferences in the solid solution as established by accurate single crystal
      diffraction studies supported by cognate powder diffraction analysis (PXRD) and
      differential scanning calorimetric (DSC) studies. A systematic study of the solid
      solution by varying the stoichiometric ratios establishes the hierarchy in
      halogen bonded motifs and consequently its directional influence to form the
      resultant supramolecular assembly.

PMID- 28766630
TI  - The dynamics of benzene on Cu(111): a combined helium spin echo and dispersion
      corrected DFT study into the diffusion of physisorbed aromatics on metal
      surfaces.
AB  - We use helium spin-echo spectroscopy (HeSE) to investigate the dynamics of the
      diffusion of benzene adsorbed on Cu(111). The results of these measurements show
      that benzene moves on the surface through an activated jump-diffusion process
      between the adsorption sites on a Bravais lattice. Density Functional Theory
      (DFT) calculations with van der Waals (vdW) corrections help us understand that
      the molecule diffuses by jumping through non-degenerate hollow sites. The results
      of the calculations shed light on the nature of the binding interaction between
      this prototypical aromatic molecule and the metallic surface. The highly accurate
      HeSE experimental data provide a quantitatively stringent benchmark for the vdW
      correction schemes applied to the DFT calculations and we compare the
      performances of several dispersion interaction schemes.

PMID- 28766631
TI  - Formation of unexpected silicon- and disiloxane-bridged multiferrocenyl
      derivatives bearing Si-O-CH[double bond, length as m-dash]CH2 and Si
      (CH2)2C(CH3)3 substituents via cleavage of tetrahydrofuran and trapping of its
      ring fragments.
AB  - The formation of a family of silicon- and siloxane-bridged multiferrocenyl
      derivatives carrying different functional groups attached to silicon, including
      Fc2(CH3)3C(CH2)2SiCH[double bond, length as m-dash]CH2 (5), Fc2(CH2[double bond,
      length as m-dash]CH-O)SiCH[double bond, length as m-dash]CH2 (6),
      Fc2(OH)SiCH[double bond, length as m-dash]CH2 (7), Fc2(CH2[double bond, length as
      m-dash]CH-O)Si-O-Si(O-CH[double bond, length as m-dash]CH2)Fc2 (8) and
      Fc2(CH2[double bond, length as m-dash]CH-O)Si-O-SiFc3 (9) is described. Silyl
      vinyl ether molecules 6, 8 and 9 and the heteroleptic vinylsilane 5 resulted from
      the competing metathesis reaction of lithioferrocene (FcLi), CH2[double bond,
      length as m-dash]CH-OLi or (CH3)3C(CH2)2Li with the corresponding multifunctional
      chlorosilane, Cl3SiCH[double bond, length as m-dash]CH2 or Cl3Si-O-SiCl3. The
      last two organolithium species have been likely formed in situ by fragmentation
      of the tetrahydrofuran solvent. Diferrocenylvinyloxyvinylsilane 6 is noteworthy
      since it represents a rare example of a redox-active silyl mononomer in which two
      different C[double bond, length as m-dash]C polymerisable groups are directly
      connected to silicon. The molecular structures of the silicon-containing
      multiferrocenyl species 5, 6, 8 and 9 have been investigated by single-crystal X
      ray diffraction studies, demonstrating the capture and storage processes of two
      ring fragments resulting from the cleavage of cyclic THF in redox-active and
      stable crystalline organometallic compounds. From electrochemical studies we
      found that by changing the anion of the supporting electrolyte from [PF6]- to
      [B(C6F5)4]-, the redox behaviour of tetrametallic disiloxane 8 can be switched
      from a poorly resolved multistep redox process to four consecutive well-separated
      one-electron oxidations, corresponding to the sequential oxidation of the four
      ferrocenyl moieties.

PMID- 28766632
TI  - Control over cyclisation sequences of 1,1'-bifunctional octamethylferrocenes to
      ferrocenophanes.
AB  - This paper describes the facile synthesis of a number of electron rich
      octamethyl[1.4]ferrocenophanes with unsaturated handles from 1,1'-bis(1
      chlorovinyl)octamethylferrocene. Treatment of this reactive compound with sodium
      hydroxide in DMF initiates a series of reactions resulting in the formation of
      four different ferrocenophanes. The most complex of these products arises from a
      cascade of cyclisations giving an unusual, unsymmetrical bis-ferrocenophane with
      a central fused cyclobutene. Control over the reaction outcome is achieved by
      manipulating the concentration of NaOH. Mechanisms are proposed, and supported by
      DFT calculations.

PMID- 28766633
TI  - Structure and reactivities of rhenium and technetium bis-arene sandwich complexes
      [M(eta6-arene)2].
AB  - Sandwich complexes are important building blocks in medicinal inorganic chemistry
      for group 6 and 8 elements but are almost unknown for the manganese triad. We
      present the syntheses and full characterization of the mixed-arene 99Tc sandwich
      complexes [99Tc(eta6-hmbz)(eta6-C6H5-NH3)](PF6)2 and [99Tc(eta6-hmbz)(eta6-C6H5
      Br)](PF6). Both comprise functionalities for conjugation to targeting molecules
      or for being included as substructures in pharmaceutically active lead compounds.
      Since eta6-benzene ligands are too stably bound to be replaced with incoming
      ligands, we prepared naphthalene complexes [Re(eta6-C6H6)(eta6-napht)]+ and
      [Re(eta6-napht)2]+. Their reactivities towards substitution are increased and one
      or both naphthalene ligands can be replaced with mono- or multi-dentate ligands.
      Combining the features of 99Tc and Re may lead to a molecule-based theranostic
      approach.

PMID- 28766635
TI  - Does the endohedral borospherene supersalt FLi2@B39 maintain the "super"
      properties of its subunits?
AB  - The behavior of the entirely unique system represented by superalkaline species
      incorporated into a superhalogen cage has been studied using density functional
      theory with hybrid functionals and the triple-xi quality basis set level of
      theory. The singlet ground state and triplet excited state of an FLi2@B39
      borospherene complex as well as its cationic and anionic doublet ground states
      have been investigated. Only the encapsulation of FLi2+ into B39 in FLi2@B39+ is
      a thermodynamically unfavorable process. All other systems are stabilized during
      encapsulation most likely via an unpaired electron delocalization process and
      electrostatic interaction. The calculations revealed that superhalogen and
      superalkaline properties inherent in the separated fragments are lost in FLi2@B39
      complexes. The applicability of vertically estimated ionization potentials and
      electron affinities instead of adiabatic ones for description of such systems has
      been demonstrated.

PMID- 28766636
TI  - Enhanced free energy of extraction of Eu3+ and Am3+ ions towards diglycolamide
      appended calix[4]arene: insights from DFT-D3 and COSMO-RS solvation models.
AB  - Density functional theory in conjunction with COSMO and COSMO-RS solvation models
      employing dispersion correction (DFT-D3) has been applied to gain an insight into
      the complexation of Eu3+/Am3+ with diglycolamide (DGA) and calix[4]arene appended
      diglycolamide (CAL4DGA) in ionic liquids by studying structures, energetics,
      thermodynamics and population analysis. The calculated Gibbs free energy for both
      Eu3+ and Am3+ ions with DGA was found to be smaller than that with CAL4DGA. The
      entropy of complexation was also found to be reduced to a large extent with DGA
      compared to complexation with CAL4DGA. The solution phase free energy was found
      to be negative and was higher for Eu3+ ion. The entropy of complexation was not
      only found to be further reduced but also became negative in the case of DGA
      alone. Though the entropy was found to be negative it could not outweigh the high
      negative enthalpic contribution. The same trend was observed in the solution
      where the free energy of extraction, DeltaG, for Eu3+ ions was shown to be higher
      than that for Am3+ ions towards free DGA. But the values of DeltaG and
      DeltaDeltaG(= DeltaGEu-DeltaGAm) were found to be much higher with CAL4DGA (
      12.58 kcal mol-1) in the presence of nitrate ions compared to DGA (-1.69 kcal mol
      1) due to enhanced electronic interaction and positive entropic contribution.
      Furthermore, both the COSMO and COSMO-RS models predict very close values of
      DeltaDeltaDeltaG (= DeltaDeltaGCAL4DGA - DeltaDeltaGnDGA), indicating that both
      solvation models could be applied for evaluating the metal ion selectivity. The
      value of the reaction free energy was found to be higher after dispersion
      correction. The charge on the Eu and Am atoms for the complexes with DGA and
      CAL4DGA indicates the charge-dipole type interaction leading to strong binding
      energy. The present theoretical results support the experimental findings and
      thus might be of importance in the design of functionalized ligands.

PMID- 28766637
TI  - Ligand-directed synthesis of {Mn} twisted bow-ties.
AB  - Two isostructural polymetallic complexes [Mn(MU3-O)2(CH3COO)4(L1)4]- and [Mn(MU3
      O)2(CH3COO)4(L2)4]- have been synthesised by using two Schiff base ligands
      derived from 3,5-diamino-1,2,4-triazole, following two different preparative
      routes, either using the pre-formed ligand (for L1) or via a metal-mediated
      template synthesis (for L2). The {Mn} structure is unusual, being based on two
      corner-sharing perpendicular {Mn3} triangles forming a twisted bow-tie. The
      magnetic studies reveal antiferromagnetic coupling between Mn(iii) ions while
      electrochemical experiments are consistent with a quasi-reversible Mn(iii)<
      >Mn(iv) redox process at the central manganese ion.

PMID- 28766638
TI  - Supramolecular chiral self-assemblies of Gly-Pro dipeptides on metallic fcc(110)
      surfaces.
AB  - Adsorption of the Glycine-Proline (Gly-Pro) dipeptide has been investigated using
      surface science complementary techniques on Au(110) and Ag(110), showing some
      interesting differences both in the chemical form and surface organization of the
      adsorbed peptide. On Au(110), Gly-Pro mainly adsorbs in neutral form (COOH/NH2),
      at low coverage or for a short interaction time; the surface species become
      zwitterionic at a higher coverage or longer interaction time. These changes are
      accompanied by a complete reorganization of the molecules at the surface. On
      Ag(110), only anionic molecules (COO-/NH2) were detected on the surface and only
      one type of arrangement was observed. These results will be compared to some
      previously obtained on Cu(110), thus providing a unique comparison of the
      adsorption of the same di-peptide on three different metal surfaces; the great
      influence of the substrate on both the chemical form and the arrangement of
      adsorbed di-peptides was made clear.

PMID- 28766639
TI  - Atomistic study of the alloying behavior of crystalline SnSe1-xSx.
AB  - Recently, layered chalcogenide alloys (LCAs) have been extensively investigated
      for use in various practical applications by selectively controlling the amount
      of foreign components. However, the alloying behavior of layered chalcogenides
      has been rarely explored at the atomistic level. Here, we study the
      microstructural evolution of SnSe1-xSx alloys on the atomic scale by combining
      scanning tunneling microscopy (STM) measurements with first-principles density
      functional theory (DFT) calculations. STM topographic images suggest that S atoms
      substituted in SnSe1-xSx are not randomly distributed, but tend to form local SnS
      clusters. The degree of S atom alloying was quantitatively estimated to be about
      60% from STM images, indicating that homo-atoms (S-S) are a preferred arrangement
      over hetero-atoms (S-Se). Our DFT calculations further confirmed that the mixing
      energy of random SnSe1-xSx alloys showed positive behavior over the whole S
      composition range considered. This result suggests that SnSe1-xSx has a tendency
      toward local phase segregation into SnSe and SnS rather than random alloys. We
      expect our atomistic study on the alloying behavior to provide important insight
      for fabricating optimal SnSe1-xSx alloys with high thermoelectric properties.

PMID- 28766640
TI  - New Au(i)-Cu(i) heterometallic complexes: the role of bridging pyridazine ligands
      in the presence of unsupported metallophilic interactions.
AB  - The reaction of the polymers [Au2Cu2(C6X5)4(NCMe)2]n (X = Cl (1), F (2)) with the
      aromatic N-donor ligand pyridazine in different molar ratios gives rise to new
      Au(i)/Cu(i) heterometallic complexes [AuCu(C6Cl5)2(MU2-C4H4N2)(NCMe)]2 (3),
      [AuCu(C6X5)2(MU2-C4H4N2)(C4H4N2)]2 (X = Cl (4), X = F (6)) and [Cu2(MU2
      C4H4N2)3(NCMe)2][Au(C6F5)2]2 (5). In all cases, the close proximity of the donor
      atoms in the diazine ligand leads to discrete molecules where two copper centres
      are connected by two or three bridging pyridazine ligands. In this way, focusing
      on the number of bridging ligands present in the molecules, unsupported closed
      shell Au(i)Cu(i) (with two bridging pyrazine ligands) or weak Cu(i)Cu(i)
      interactions (with three bridging pyridazines) have been observed. None of these
      pyridazine derivatives is luminescent, which is probably related to the absence
      of aurophilic contacts.

PMID- 28766641
TI  - Complex self-propelled rings: a minimal model for cell motility.
AB  - Collective behavior of active matter is observed for self-propelled particles,
      such as vibrated disks and active Brownian particles, as well as for cytoskeletal
      filaments in motile cells. Here, a system of quasi two-dimensional penetrable
      self-propelled rods inside rigid rings is used to construct a complex self
      propelled particle. The rods interact sterically with each other and with a
      stationary or mobile ring via a separation-shifted Lennard-Jones potential. They
      either have a sliding attachment to the inside of the ring at one of their ends,
      or can move freely within the ring confinement. We study the inner structure and
      dynamics of the mobile self-propelled rings. We find that these complex particles
      cannot only be characterized as active Brownian particles, but can also exhibit
      cell-like motility: random walks, persistent motion, circling, and run-and-circle
      motion.

PMID- 28766643
TI  - The inter-micellar interaction enthalpies of DTAB/TX100 mixed micelles and their
      structural transitions.
AB  - The heats of mixing for a series of DTAB/TX100 mixed surfactant aqueous solutions
      were measured by flow-mixing calorimetry and isothermal titration calorimetry
      (ITC) at 298.15 K and 85 kPa, which were used to calculate the inter-micellar
      interaction enthalpies (-DeltaHC). The signs of -DeltaHC for pure DTAB and TX100
      micellar systems were contrary to the inter-micellar interaction parameters
      reported for the same systems in the literature, suggesting that these
      interaction parameters might have a Gibbs free energy character dominated by
      entropy changes. It was found that the inter-micellar interaction enthalpies
      varied with the total surfactant concentration and the mixed ratio of the two
      surfactants, and characterized different structures of the mixed micelles. These
      phenomena were discussed based on the effects of structural water around the
      micellar interface, the hydration of counterions, and the repulsive Coulombic
      interaction.

PMID- 28766644
TI  - Nonlinear effects at the soft interface of an emulsion in the List-Lerner-Barbas
      aldol reaction.
AB  - Nonlinear effects have been observed for the List-Lerner-Barbas aldol reaction
      catalyzed by a proline-based surfactant catalyst at the aqueous-organic interface
      under emulsifying conditions. The differential partitioning of the amphiphilic
      catalyst enantiomers at the interfacial assembly leads to deracemization at the
      soft interface of an emulsion. The effect cascades to the interfacial chemical
      processes, which reflect the asymmetry of the interacting chiral assembly. The
      observations establish that soft interfaces such as those present in an emulsion
      can present a platform for inducing asymmetric partitioning of catalysts and
      hence, lead to an apparently nonlinear trend in the induced chirality for
      interfacial processes.

PMID- 28766645
TI  - Sensing of NO2 with zirconium hydroxide via frequency-dependent electrical
      impedance spectroscopy.
AB  - Zirconium hydroxide has been investigated as a candidate nitrogen dioxide
      dielectric sensor using impedance spectroscopy analysis. Significant changes in
      electronic and physical properties down to our dosage minimum of 2 ppm h have
      been observed. Using disc-shaped pressed pellets of Zr(OH)4 in parallel plate
      geometry, we observe a maximum signal shift of 35% at 2 ppm h dosage, which
      increases six orders of magnitude as the dosage reaches 1000 ppm h. Changes in
      impedance correlate with nitrogen and oxygen atomic ratio increases observed via
      X-ray photoelectron spectroscopy (XPS) at higher NO2 dosages. In contrast to the
      sharp frequency-dependent features and net impedance decreases during NO2
      exposures, Zr(OH)4 exhibits a large and broad impedance increase after exposure
      to humid air (water vapor). The results indicate that Zr(OH)4 could be used as a
      selective low-cost impedance-based NO2 detector by applying frequency-dependent
      impedance fingerprinting.

PMID- 28766646
TI  - A cascade enzymatic reaction activatable gemcitabine prodrug with an AIE-based
      intracellular light-up apoptotic probe for in situ self-therapeutic monitoring.
AB  - A targeted cathepsin B-activatable gemcitabine prodrug with caspase-3 specific
      light-up tetraphenylene (TPE) as an apoptotic probe based on aggregation-induced
      emission (AIE) properties was designed for in situ self-therapeutic monitoring of
      pancreatic cancer cells.

PMID- 28766647
TI  - Facile functionalization of peptide nucleic acids (PNAs) for antisense and single
      nucleotide polymorphism detection.
AB  - In this report, we show how a convenient on-resin copper-click functionalization
      of azido-functionalized peptide nucleic acids (PNAs) allows various PNA-based
      detection strategies. Firstly, a thiazole orange (TO) clicked PNA probe
      facilitates a binary readout when combined with F/Q labeled DNA, giving increased
      sensitivity for antisense detection. Secondly, our TO-PNA conjugate also allows
      single nucleotide polymorphism detection. Since antisense detection is also
      possible in the absence of the TO label, our sensing platform based on azido-d
      ornithine containing PNA even allows for additional and more advanced
      functionalization and sensing strategies.

PMID- 28766648
TI  - Enzyme-instructed self-assembly with photo-responses for the photo-regulation of
      cancer cells.
AB  - Using a short peptide precursor modified by the biaryltetrazole with
      intramolecular photo-click reactivity, we realized the photo-regulation of the
      pericellular nanofibers formed by the enzyme-instructed self-assembly on the cell
      membrane. Upon light irradiation, the fluorescence of nanofibers could be turned
      on to monitor both enzyme-instructed self-assembly and photo-induced disassembly
      processes. Moreover, the cell fate could be controlled through the photo
      regulation.

PMID- 28766649
TI  - A triple action chemosensor for Cu2+ by chromogenic, Cr3+ by fluorogenic and CN-
      by relay recognition methods with bio-imaging of HeLa cells.
AB  - A triple action chemosensor (R1) bearing a rhodamine and thiophene moiety was
      synthesized by a simple condensation reaction. The sensing behaviour and
      selectivity of the synthesized chemosensor toward metal ions were studied by UV
      Vis and fluorescence spectroscopy. The chemosensor recognized Cu2+ and Cr3+ ions
      with significant changes in UV-Vis absorbance and fluorescence intensity. The
      results showed that Cr3+ induced greater fluorescence enhancement whereas Cu2+
      ions bound strongly with the receptor by showing a strong absorption band at 554
      nm but with weak fluorescence. A visible colour change was observed by the
      addition of Cu2+ and that colour change is due to the opening of the spirolactam
      ring triggered by the addition of Cu2+ ions. Job's plot analysis indicated a 1 :
      2 and 1 : 1 binding stoichiometry between the chemosensor and Cr3+/Cu2+.
      Subsequently, the R1 - Cu2+ complex chemosensor was employed to detect CN- in the
      presence of different anions, such as F-, Cl-, Br-, I-, AcO-, H2PO4-, HSO4-, NO3-
      and -OH. In addition, the live cell imaging of HeLa cells using R1 and Cr3+ was
      demonstrated successfully.

PMID- 28766650
TI  - A new strategy to engineer polymer bulk heterojunction solar cells with thick
      active layers via self-assembly of the tertiary columnar phase.
AB  - We report that the addition of a non-photoactive tertiary polymer phase in the
      binary bulk heterojunction (BHJ) polymer solar cell leads to a self-assembled
      columnar nanostructure, enhancing the charge mobilities and photovoltaic
      efficiency with surprisingly increased optimal active blend thicknesses over 300
      nm, 3-4 times larger than that of the binary counterpart. Using the prototypical
      poly(3-hexylthiophene) (P3HT):fullerene blend as a model BHJ system, we discover
      that the inert poly(methyl methacrylate) (PMMA) added in the binary BHJ blend
      self-assembles into vertical columns, which not only template the phase
      segregation of electron acceptor fullerenes but also induce the out-of-plane
      rotation of the edge-on-orientated crystalline P3HT phase. Using complementary
      interrogation methods including neutron reflectivity, X-ray scattering, atomic
      force microscopy, transmission electron microscopy, and molecular dynamics
      simulations, we show that the enhanced charge transport originates from the more
      randomized molecular stacking of the P3HT phase and the spontaneous segregation
      of fullerenes at the P3HT/PMMA interface, driven by the high surface tension
      between the two polymeric components. The results demonstrate a potential method
      for increasing the thicknesses of high-performance polymer BHJ solar cells with
      improved photovoltaic efficiency, alleviating the burden of stringently
      controlling the ultrathin blend thickness during the roll-to-roll-type large-area
      manufacturing environment.

PMID- 28766651
TI  - Thermal rectification at the bimaterial nanocontact interface.
AB  - Thermal rectification can help develop modern thermal manipulation devices but
      has been rarely engineered. Here, we validated the nanoscale bimaterial interface
      induced thermal rectification experimentally for the first time and investigated
      its underlying mechanism via molecular dynamics simulations. The thermal diode
      consists of polyamide (PA) and silicon (Si) nanowires in contact with each other.
      The thermal rectification ratio measured by a high-precision nanoscale experiment
      reached 4% with an uncertainty of <1%. The temperature has little influence on
      the ratio, while the decrease in contact length or increase in temperature
      differences can increase the ratio. The molecular dynamics simulations further
      confirmed the thermal rectification in the PA/Si nanowires. We found that the
      localized modes generally gather on the edge, and the higher extent of phonon
      localization is responsible for the lower thermal conductance in the thermal
      rectification. Our findings not only have guiding significance, but can also
      promote the development of interface-based solid-state thermal diodes.

PMID- 28766652
TI  - Efficient active-template synthesis of calix[6]arene-based oriented
      pseudorotaxanes and rotaxanes.
AB  - A substrate can modify its chemical features, including a change of its
      reactivity, as a consequence of non-covalent interactions upon inclusion within a
      molecular host. Since the rise of supramolecular chemistry, this phenomenon has
      stimulated the ingenuity of scientists to emulate the function of enzymes by
      designing supramolecular systems in which the energetics and selectivity of
      reactions can be manipulated through programmed host-guest interactions and/or
      steric confinement. In this paper we investigate how the engulfment of a
      positively charged pyridinium-based guest inside the pi-rich cavity of a tris-(N
      phenylureido)calix[6]arene host affects its reactivity towards a SN2 reaction. We
      found that the alkylation of complexed substrates leads to the formation of
      pseudorotaxanes and rotaxanes with faster kinetics and higher yields with respect
      to the standard procedures exploited so far. More importantly, the strategy
      described here expands the range of efficient synthetic routes for the formation
      of mechanically interlocked species with a strict control of the mutual
      orientation of their non-symmetric molecular components.

PMID- 28766653
TI  - Controllable multicompartment morphologies from cooperative self-assembly of
      copolymer-copolymer blends.
AB  - Multicompartment nanostructures, such as microcapsules with clearly separated
      shell and core, are not easily accessible by conventional block copolymer self
      assembly. We assess a versatile computational strategy through cooperative
      assembly of diblock copolymer blends to generate spherical and cylindrical
      compartmentalized micelles with intricate structures and morphologies. The co
      assembly strategy combines the advantages of polymer blending and incompatibility
      induced phase separation. Following this strategy, various nanoassemblies of pure
      AB, binary AB/AC and ternary AB/AC/AD systems such as compartmentalized micelles
      with sponge-like, Janus, capsule-like and onion-like morphologies can be
      obtained. The formation and structural adjustment of microcapsule micelles, in
      which the shell or core can be occupied by either pure or mixed diblock
      copolymers, were explored. The mechanism involving the separation of shell and
      core copolymers is attributed to the stretching force differences of copolymers
      which drive the arrangement of different copolymers in a pathway to minimize the
      total interfacial energy. Moreover, by adjusting block interactions, an efficient
      approach is exhibited for regulating the shell or core composition and morphology
      in microcapsule micelles, such as the transition from the "pure shell/mixed core"
      morphology to the "mixed shell/pure core" morphology in the AB/AC/AD micelle.
      This mesoscale simulation study identifies the key factors governing co-assembly
      of diblock copolymer blends and provides bottom-up insights towards the design
      and optimization of new multicompartment micelles.

PMID- 28766654
TI  - Fabrication and improved photoelectrochemical properties of a transferred GaN
      based thin film with InGaN/GaN layers.
AB  - Herein, a lift-off mesoporous GaN-based thin film, which consisted of a strong
      phase-separated InGaN/GaN layer and an n-GaN layer, was fabricated via an
      electrochemical etching method in a hydrofluoric acid (HF) solution for the first
      time and then transferred onto quartz or n-Si substrates, acting as photoanodes
      during photoelectrochemical (PEC) water splitting in a 1 M NaCl aqueous solution.
      Compared to the as-grown GaN-based film, the transferred GaN-based thin films
      possess higher and blue-shifted light emission, presumably resulting from an
      increase in the surface area and stress relaxation in the InGaN/GaN layer
      embedded on the mesoporous n-GaN. The properties such as (i) high photoconversion
      efficiency, (ii) low turn-on voltage (-0.79 V versus Ag/AgCl), and (iii)
      outstanding stability enable the transferred films to have excellent PEC water
      splitting ability. Furthermore, as compared to the film transferred onto the
      quartz substrate, the film transferred onto the n-Si substrate exhibits higher
      photoconversion efficiency (2.99% at -0.10 V) due to holes (h+) in the mesoporous
      n-GaN layer that originate from the n-Si substrate.

PMID- 28766655
TI  - Ionic liquids for metal extraction from chalcopyrite: solid, liquid and gas phase
      studies.
AB  - We studied leaching of Cu and Fe from naturally occurring chalcopyrite ore using
      aqueous solutions of ionic liquids (ILs) based on imidazolium and ethylammonium
      cations and hydrogensulfate, nitrate, acetate or dicyanamide anions. Liquid,
      solid and gas phases of the leaching systems were characterised. We have shown
      that nonoxidative leaching is greatly dependant not only on temperature and pH,
      but on the anion species of the IL. Solutions of 1-butylimidazolium hydrogen
      sulfate exhibited the best leaching performance among hydrogen sulphate ILs. We
      have suggested that the formation of an oxide layer in some ILs may be
      responsible for a reduced leaching ability. The analysis of the gas phase showed
      the production of CO2 and CS2 in all leached samples. Our results suggested that
      the CS2 produced upon leaching could be responsible for decreasing the sulfur,
      but not oxide, layer on the surface of chalcopyrite samples and therefore more
      efficient leaching. This is the first study, to our knowledge, to provide a
      systematic comparison of the leaching performance of ILs composed of different
      anions and cations and without added oxidants.

PMID- 28766656
TI  - Amide rotation trajectories probed by symmetry.
AB  - Amide rotation of peptidyl-prolyl fragments is an important factor in backbone
      structure organization of proteins. Computational studies have indicated that
      this rotation preferentially proceeds through a defined transition-state
      structure (syn/exo). Here, we complement the computational findings by
      determining the amide bond rotation barriers for derivatives of the two symmetric
      proline analogues, meso and racemic pyrrolidine-2,5-dicarboxylic acids. The
      rotations around these residues represent syn/exo-syn/exo and anti/endo-syn/exo
      hybrid transition states for the meso and racemic diastereomer, respectively. The
      rotation barriers are lower for the former rotation by about 9 kJ mol-1 (aqueous
      medium), suggesting a strong preference for the syn/exo (clockwise) rotation over
      the anti/endo (anticlockwise) rotation. The results show that both hybrid
      rotation processes are enthalpically driven but respond differently to solvent
      polarity changes due to the different transition state dipole-dipole
      interactions.

PMID- 28766657
TI  - Surface functionalisation of polymers.
AB  - Many applications of polymers require the functionalisation of their surface for
      use in sensors, composite materials, membranes, microfluidic and biomedical
      devices and many others. Such surface modifications endow the surface with new
      properties independent of those of the bulk polymer. This tutorial review
      describes the different methods, based on very diverse principles, that are
      available to perform this surface functionalisation, including plasma and UV
      irradiation, atomic layer deposition, electrochemistry, oxidation, reduction,
      hydrolysis, the use of radicals and grafting "on" or "from" polymers. The
      principles of the different methods are briefly described and many examples are
      given to highlight the possibilities of the methods and the possible
      applications. A section is devoted to the surface modification of polymeric
      nanoparticles.

PMID- 28766659
TI  - Hole doping, hybridization gaps, and electronic correlation in graphene on a
      platinum substrate.
AB  - The interaction between graphene and substrates provides a viable route to
      enhance the functionality of both materials. Depending on the nature of
      electronic interaction at the interface, the electron band structure of graphene
      is strongly influenced, allowing us to make use of the intrinsic properties of
      graphene or to design additional functionalities in graphene. Here, we present an
      angle-resolved photoemission study on the interaction between graphene and a
      platinum substrate. The formation of an interface between graphene and platinum
      leads to a strong deviation in the electronic structure of graphene not only from
      its freestanding form but also from the behavior observed on typical metals. The
      combined study on the experimental and theoretical electron band structure
      unveils the unique electronic properties of graphene on a platinum substrate,
      which singles out graphene/platinum as a model system investigating graphene on a
      metallic substrate with strong interaction.

PMID- 28766660
TI  - The spatial arrangement of a single nanoparticle in a thin polymer film and its
      effect on the nanoparticle diffusion.
AB  - The spatial arrangement of nanoparticles (NPs) within thin polymer films may
      influence their properties such as the glass transition temperature. Questions
      regarding what may affect the spatial arrangement of NPs, however, still remain
      unanswered at a molecular level. In this work, we perform molecular dynamics
      simulations for a free-standing thin polymer film with a single NP. We find from
      simulations that depending on the NP size and the inter-particle interaction
      between the NP and polymers, one may control the spatial arrangement of the NP.
      When the interaction between the NP and polymers is sufficiently attractive
      (repulsive), the NP is likely to be placed at the center (at the surface) of the
      thin film in equilibrium. Interestingly, for a moderate interaction between the
      NP and polymers, the first-order transition occurs in the spatial arrangement of
      the NP as one increases the NP size: a small NP prefers the surface of the
      polymer film whereas a large NP prefers the center. Such a first-order transition
      is corroborated by calculating the free energy of the NP as a function of the
      position and can be understood in terms of a sixth-order Landau free energy. More
      interestingly, the diffusion of the NP also changes drastically due to the first
      order transition in the spatial arrangement. The NP diffusion is enhanced
      drastically (more than expected in bulk polymer melts) as the NP is shifted to
      the polymer film surface.

PMID- 28766663
TI  - Promoted photoelectrocatalytic hydrogen evolution of a type II structure via an
      Al2O3 recombination barrier layer deposited using atomic layer deposition.
AB  - Constructing a semiconductor type II structure is an effective way to enhance the
      photogenerated charge separation efficiency. The separation and migration of
      interfacial photogenerated carriers is a key factor, which influences the
      photocatalytic activity. In this study, a conformal Al2O3 recombination barrier
      layer was introduced at the interface between TiO2 nanowires and CdSe
      nanoparticles, and the application of this composite in photoelectrocatalytic
      (PEC) hydrogen production was explored. Under visible-light irradiation, the
      photocurrent response and PEC hydrogen evolution performance increased step-by
      step from TiO2 to the Al2O3/TiO2 and CdSe/Al2O3/TiO2 nanowire arrays. Moreover,
      the H2 evolution rate of CdSe/Al2O3/TiO2 was much higher than that of a different
      configuration, Al2O3/CdSe/TiO2. The enhanced PEC hydrogen evolution performance
      was attributed to the prevention of the interfacial charge recombination caused
      by the Al2O3 recombination barrier layer. Our results may shed new light on
      developing novel and highly efficient photocatalysts using rational interface
      design.

PMID- 28766664
TI  - Tetrahydrocurcumin is more effective than curcumin in inducing the apoptosis of
      H22 cells via regulation of a mitochondrial apoptosis pathway in ascites tumor
      bearing mice.
AB  - Curcumin (CUR), a widely used food additive, is derived mainly from Curcuma
      species that has been applied traditionally for the treatment of various
      diseases, including hepatocellular carcinoma (HCC). However, its poor systemic
      bioavailability hampers its clinical application, which may be related to its
      wide metabolism. Tetrahydrocurcumin (THC) is a major metabolite of CUR and has
      been reported to have multiple biologic activities. We investigated, for the
      first time, the efficacy and associated mechanism of action of THC and CUR in a
      H22 ascites tumor-bearing model in mice. THC evoked a significant dose-dependent
      promotion of survival and was significantly more effective than CUR in inhibiting
      tumor growth, including increased body weight, abdominal circumference, ascites
      volume, and the viability of cancer cells. Experiments on essential immune organs
      indicated that THC had a more favorable margin of safety than the reference drug
      cyclophosphamide. THC induced the apoptosis of H22 cells obviously by increasing
      the level of p53 and decreasing the level of murine double minute 2. THC also
      decreased the expression of Bcl-2 significantly and increased the expression of
      Bcl2-associated X, resulting in the release of cytochrome C. THC significantly
      activated and induced cleavage of caspase-3 and caspase-9 to induce the apoptosis
      of H22 cells. Taken together, these results indicate that THC was more effective
      than CUR in inhibiting the apoptosis of H22-induced ascites tumor cells and
      achieved it via regulation of a mitochondrial apoptosis pathway. THC might be a
      bioactive anti-tumor form of CUR and represented a potentially effective agent
      for HCC treatment.

PMID- 28766666
TI  - Urchin-like hierarchical H-Nb2O5 microspheres: synthesis, formation mechanism and
      their applications in lithium ion batteries.
AB  - Urchin-like hierarchical Nb2O5 microspheres are successfully synthesized through
      a facile solvothermal method in glycerol-isopropanol mixed media followed by
      thermal treatment. The sample is characterized by XRD, FESEM, TEM, HRTEM, BET,
      and XPS, and the results reveal that the as-formed Nb2O5 microspheres have a
      pseudohexagonal structure and are composed of nanorods with an average diameter
      of ca. 20 nm. It is found that glycerol not only serves as a solvent but also
      acts as a reactant; furthermore, isopropanol plays an important part in the
      morphologies of the products. When used as anodic materials for lithium ion
      batteries, the Nb2O5 microspheres deliver initial discharge capacities of 201.7,
      159.7, 148.5, 123.7, and 98.5 mA h g-1 at the current densities of 0.5, 1, 2, 5,
      and 10C, respectively. Additionally, the discharge capacity of Nb2O5 remains at
      105.5 mA h g-1 even after 500 cycles at a high rate of 5C. The good
      electrochemical properties of the products may be ascribed to their large surface
      areas and hierarchical structures.

PMID- 28766667
TI  - Influence of polymer architectures on diffusion in unentangled polymer melts.
AB  - Recent simulations have indicated that the thermodynamic properties and the
      glassy dynamics of polymer melts are strongly influenced by the average molecular
      shape, as quantified by the radius of gyration tensor of the polymer molecules,
      and that the average molecular shape can be tuned by varying the molecular
      topology (e.g., ring, star, linear chain, etc.). In the present work, we
      investigate if the molecular shape is similarly a predominant factor in
      understanding the polymer center of mass diffusion D in the melt, as already
      established for polymer solutions. We find that all our D data for unentangled
      polymer melts having a range of topologies can be reasonably described as a power
      law of the polymer hydrodynamic radius, Rh. In particular, this scaling is
      similar to the scaling of D for a tracer sphere having a radius on the order of
      the chain radius of gyration, Rg. We conclude that the chain topology influences
      the molecular dynamics in as much as the polymer topology influences the average
      molecular shape. Experimental evidence seems to suggest that this situation is
      also true for entangled polymer melts.

PMID- 28766669
TI  - Broadband room temperature strong coupling between quantum dots and
      metamaterials.
AB  - Herein, we report the first demonstration of room temperature enhanced light
      matter coupling in the visible regime for metamaterials using cooperative coupled
      quasi two dimensional quantum dot assemblies located at precise distances from
      the hyperbolic metamaterial (HMM) templates. The non-monotonic variation of the
      magnitude of strong coupling, manifested in terms of strong splitting of the
      photoluminescence of quantum dots, can be explained in terms of enhanced LDOS
      near the surface of such metamaterials as well as the plasmon mediated super
      radiance of closely spaced quantum dots (QDs). Our methodology of enhancing
      broadband, room temperature, light-matter coupling in the visible regime for
      metamaterials opens up new possibilities of utilising these materials for a wide
      range of applications including QD based thresholdless nanolasers and novel
      metamaterial based integrated photonic devices.

PMID- 28766671
TI  - Preparation of two dimensional layered double hydroxide nanosheets and their
      applications.
AB  - Layered double hydroxides (LDHs) with their highly flexible and tunable chemical
      composition and physical properties have attracted tremendous attention in recent
      years. LDHs have found widespread application as catalysts, anion exchange
      materials, fire retardants, and nano-fillers in polymer nanocomposites. The
      ability to exfoliate LDHs into ultrathin nanosheets enables a range of new
      opportunities for multifunctional materials. In this review we summarize the
      current available LDH exfoliation methods. In particular, we highlight recent
      developments for the direct synthesis of single-layer LDH nanosheets, as well as
      the emerging applications of LDH nanosheets in catalyzing oxygen evolution
      reactions and preparing light emitting devices, supercapacitors, and flame
      retardant nanocomposites.

PMID- 28766668
TI  - Exploring the effect of hydroxylic and non-hydroxylic solvents on the reaction of
      [VIVO(beta-diketonate)2] with 2-aminobenzoylhydrazide in aerobic and anaerobic
      conditions.
AB  - Refluxing [VIVO(beta-diketonate)2], namely [VIVO(acetylacetonate)2] and
      [VIVO(benzoylacetonate)2], separately with an equivalent or excess amount of 2
      aminobenzoylhydrazide (ah) in laboratory grade (LG) CH3OH in aerobic conditions
      afforded non-oxidovanadium(iv) and oxidovanadium(v) complexes of the type
      [VIV(L1)2] (1), [VVO(L1)(OCH3)]2 (3) and [VIV(L2)2] (2), and [VVO(L2)(OCH3)] (4),
      respectively. (L1)2- and (L2)2- represent the dianionic forms of 2
      aminobenzoylhydrazone of acetylacetone (H2L1) and benzoylacetone (H2L2),
      respectively, (general abbreviation, H2L), which was formed by the in situ
      condensation of ah with the respective coordinated [beta-diketonate] in medium-to
      good yield. The yield of different resulting products was dependent upon the
      ratio of ah to [VIVO(beta-diketonate)2]. For example, the yield of 1 and 2
      complexes increased significantly associated with a decrease in the amount of 3
      and 4 with an increase in the molar ratio of ah. Upon replacing CH3OH by a non
      hydroxylic solvent, LG CHCl3, the above reaction yielded only oxidovanadium(v)
      complexes of the type [VVO(L1)(OH)]2 (5), [VVO(L2)(OH)] (6) and [VO3(L)2] (7, 8)
      whereas, upon replacing CHCl3 by another non-hydroxylic solvent, namely LG CH3CN,
      only the respective [VO3(L)2] (7, 8) complex was isolated in 72-78% yield.
      However, upon performing the above reactions in the absence of air using dry
      CH3OH or dry CHCl3, only the respective [VIV(L)2] complex was obtained,
      suggesting that aerial oxygen was the oxidising agent and the type of pentavalent
      product formed was dependent upon the nature of solvent used. Complexes 3 and 4
      were converted, respectively, to 7 and 8 on refluxing in LG CHCl3via the
      respective unstable complex 5 and 6. The DFT calculated change in internal energy
      (DeltaE) for the reactions 2[VVO(L2)(OCH3)] + 2H2O -> 2[VVO(L2)(OH)] + 2CH3OH and
      2[VVO(L2)(OH)] -> [VO3(L2)2] + H2O was, respectively, +3.61 and -7.42 kcal mol-1,
      suggesting that the [VVO(L2)(OH)] species was unstable and readily transformed to
      the stable [VO3(L2)2] complex. Upon one-electron reduction at an appropriate
      potential, each of 7 and 8 generated mixed-valence [(L)VVO-(MU-O)-OVIV(L)]-
      species, which showed valence-delocalisation at room temperature and localisation
      at 77 K. Some of the complexes showed a wide range of toxicity in a dose
      dependent manner against lung cancer cells comparable with that observed with cis
      platin.

PMID- 28766673
TI  - Generation and characterization of monodisperse deformable alginate and pNIPAM
      microparticles with a wide range of shear moduli.
AB  - Monodisperse particles of varying size, shape, and deformability were produced
      using two microfluidic strategies. For both strategies, monodisperse emulsion
      droplets of a crosslinkable solution were generated via flow-focusing.
      Subsequently, droplets were crosslinked either on chip or in an external bath. On
      chip gelation resulted in spherical particles; varying the degree of crosslinking
      varied the deformability systematically. The optimized flow-focusing device
      design separated the production of monodisperse aqueous alginate droplets and the
      on-chip introduction of crosslinking ions. Two features were then adapted to
      target softer particles: the dispersed phase design and the polymer choice. The
      alternative design used a sheathed dispersed phase, with the polymer solution
      surrounding an unreactive viscous core, which generated alginate particles with a
      softer core. Poly(N-isopropylacrylamide) (pNIPAM) allowed access to a broad range
      of moduli. The resulting spherical particles were characterized using capillary
      micromechanics to determine the shear (G) and compressive (K) moduli. Particles
      with G = 0.013 kPa to 26 kPa and K = 0.221 kPa to 34.9 kPa were obtained; the
      softest particles are an order of magnitude softer than those previously
      reported. The second approach, based on earlier work by Hu et al., produced
      axisymmetric, non-spherical particles with fore-aft asymmetry. Alginate drops
      were again formed in a flow-focusing device but were crosslinked off-chip in an
      external gelation bath. By changing the bath viscosity, crosslinker
      concentration, and outlet height, the falling droplets deformed differently
      during gelation, resulting in a variety of shapes, such as teardrop, mushroom,
      and bowl shapes.

PMID- 28766672
TI  - Seabuckthorn berry polysaccharide protects against carbon tetrachloride-induced
      hepatotoxicity in mice via anti-oxidative and anti-inflammatory activities.
AB  - The berries of Seabuckthorn (Hippophae rhamnoides L.) are traditional medicinal
      foods that have been used by Tibetans and Mongolians for thousands of years. The
      polysaccharides are the main components of Seabuckthorn berries, possessing
      immune stimulating, anti-cancer and anti-fatigue activities. The present study
      focused on evaluating the protective effects and mechanisms of Seabuckthorn berry
      polysaccharide (SP) against carbon tetrachloride (CCl4)-induced hepatotoxicity.
      Mice were orally administrated with 50, 100 and 200 mg kg-1 of SP once daily for
      14 consecutive days prior to CCl4 challenge. Pretreatment with SP significantly
      decreased alanine transaminase (ALT), aspartate aminotransferase (AST) and total
      bilirubin (TBIL) levels, while increasing the levels of prealbumin (PALB) in the
      CCl4-challenged mice, which were accompanied by diminished liver injuries,
      increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)
      activities, increased GSH levels, and reduced malondialdehyde (MDA) content. The
      pretreatment with SP also markedly reduced the CCl4-induced expression of tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), inducible
      nitric oxide synthase (iNOS) and nitric oxide (NO). Furthermore, the pretreatment
      with SP decreased hepatic Toll-like receptor 4 (TLR4) expression and inhibited
      the phosphorylation of p38 MAPK, extracellular signal-regulated kinase (p-ERK), c
      Jun N-terminal kinase (p-JNK) and nuclear factor-kappa B (NF-kappaB) in the CCl4
      challenged mice. These results suggest that the pretreatment with SP protected
      against CCl4-induced liver damage via its anti-oxidative and anti-inflammatory
      activities. SP might be suitable for functional foods and natural drugs in
      preventing CCl4-induced hepatotoxicity.

PMID- 28766674
TI  - A mononuclear Co(ii) complex formed from pyridinedimethanol with manifold slow
      relaxation channels.
AB  - A mononuclear hexacoordinate complex [Co(pydm)2](dnbz)2 formed from 2,6
      pyridinedimethanol in the coordination sphere of Co(ii) and dinitrobenzoato
      anions exhibits magnetic anisotropy of an easy axis type and a field induced slow
      magnetic relaxation with manifold relaxation channels. The low-frequency
      relaxation time is as slow as tauLF = 0.13 s at BDC = 0.4 T and T = 1.9 K.

PMID- 28766676
TI  - Surface induced crystallization of polymeric nano-particles: effect of surface
      roughness.
AB  - Molecular dynamics simulations are conducted to study the crystallization of a
      polymeric system as a drop in an isolated state and on a surface. It is shown
      that crystallization kinetics for the polymeric system as a particle on a smooth
      surface is much faster than in the isolated form. We show however that as the
      surface becomes rough the crystallization rate of the polymeric particle
      decreases. The effect of roughness was compared for two cases of a polymer drop,
      partially (Wenzel state) and fully (fully confined) wetting the cavities on a
      rough surface. In both cases it was observed that crystallization was slower than
      that on a smooth surface, and crystal growth rate was decreased by increasing the
      characteristic roughness ratio. The crystallization on rough surfaces was still
      faster than that of the isolated polymer drop.

PMID- 28766677
TI  - Vibrational contributions to intrinsic friction in charged transition metal
      dichalcogenides.
AB  - Vibrational contributions to intrinsic friction in layered transition metal
      dichalcogenides (TMDs) have been studied at different charge contents. We find
      that any deviation from charge neutrality produces complex rearrangements of
      atomic positions and electronic distributions, and consequent phase transitions.
      Upon charge injection, cell volume expansion is observed, due to charge
      accumulation along an axis orthogonal to the layer planes. Such accumulation is
      accounted for by the d3z2-r2 orbital of the transition metal and it is regulated
      by the Pt2g,eg orbital polarization. The latter, in turn, determines the
      frequency of the phonon modes related to the intrinsic friction through non
      trivial electro-vibrational coupling. The bond covalency and atom pair
      cophonicity can be exploited as a knob to control such coupling, ruling subtle
      charge flows through atomic orbitals hence determining vibrational frequencies at
      a specific charge content. The results can be exploited to finely tune
      vibrational contributions to intrinsic friction in TMD structures, in order to
      facilitate assembly and operation of nanoelectromechanical systems and,
      ultimately, to govern electronic charge distribution in TMD-based devices for
      applications beyond nanoscale tribology.

PMID- 28766678
TI  - Identification of hispidin as a bioluminescent active compound and its recycling
      biosynthesis in the luminous fungal fruiting body.
AB  - We previously showed that luminous fungi share a common mechanism in
      bioluminescence, and identified hispidin as a luciferin precursor in
      Neonothopanus nambi mycelium. Here we showed the presence of hispidin as a
      bioluminescent active compound at 25-1000 pmol g-1 in the fruiting bodies of
      Mycena chlorophos, Omphalotus japonicus, and Neonothopanus gardneri. These
      results suggest that luminous mushrooms contain hispidin as a luciferin
      precursor. We also found that non-luminous "young" fruiting bodies exhibited
      luminescence by hispidin treatment. Furthermore, we observed a gradual
      luminescence enhancement of the cell-free fruiting body extract by the addition
      of hispidin biosynthetic components, namely caffeic acid, ATP and malonyl-CoA.
      These findings suggest that continuous weak glow of luminous mushrooms is
      regulated by slow recycling biosynthesis of hispidin.

PMID- 28766679
TI  - Neutron reflectometry yields distance-dependent structures of nanometric polymer
      brushes interacting across water.
AB  - The interaction between surfaces displaying end-grafted hydrophilic polymer
      brushes plays important roles in biology and in many wet-technological
      applications. In this context, the conformation of the brushes upon their mutual
      approach is crucial, because it affects interaction forces and the brushes' shear
      tribological properties. While this aspect has been addressed by theory,
      experimental data on polymer conformations under confinement are difficult to
      obtain. Here, we study interacting planar brushes of hydrophilic polymers with
      defined length and grafting density. Via ellipsometry and neutron reflectometry
      we obtain pressure-distance curves and determine distance-dependent polymer
      conformations in terms of brush compression and reciprocative interpenetration.
      While the pressure-distance curves are satisfactorily described by the Alexander
      de-Gennes model, the pronounced brush interpenetration as seen by neutron
      reflectometry motivates detailed simulation-based studies capable of treating
      brush interpenetration on a quantitative level.

PMID- 28766680
TI  - The structure of liquid alkali nitrates and nitrites.
AB  - High energy X-ray diffraction has been combined with containerless techniques to
      determine the structure of a series of alkali and ammonium nitrate and nitrite
      liquids. The systems have been modelled using molecular dynamics simulation which
      allows for the flexibility of, and movement of charge within, the molecular
      anions. The model reproduces the experimentally-determined scattering functions
      in both the low- and high-Q regimes reflecting the inter- and intra-molecular
      length-scales. For ammonium nitrate the best fit to the diffraction data is
      obtained by assuming the NH4+ cation to have a radius closer to that for Cs+
      rather than a smaller cation such as Rb+ as often previously assumed. The alkali
      nitrites show an emergent length scale, attributed to the nitrogen-nitrogen
      spatial correlations, that depends on both temperature and the identity of the
      alkali cation. The corresponding nitrates show a more subtle effect in the
      nitrogen-nitrogen correlations. As a result, the nature of this N-N length-scale
      appears different for the respective nitrites and nitrates.

PMID- 28766682
TI  - FasR and FasL in colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most common solid organ cancers prevalent
      worldwide causing, in spite of advancing therapeutic methodology, high rate of
      patient mortality, especially due to metastasis development. The cancer stem cell
      (CSC) theory of tumor growth indicates that CSCs within the tumor mass have great
      capacity to initiate and sustain tumor growth. Following the suggestion that Fas
      signaling can be engaged in apoptosis, tumor maintenance, senescence or DICE
      (death induced by CD95 or CD95L elimination), the attempts to broaden the
      knowledge concerning the relationships between CSCs features and FasR/FasL
      appeared to be necessary. The most important advantage of our study was the
      simultaneously analysis of CSCs from commonly used CRC lines (HCT116 and HT29)
      and tumor fragments collected from CRC patients. Moreover, the sphere-promoting
      expansion of CRC lines brought a specific three-dimensional specific environment
      for CSC exploration. We further investigated the function of Fas signaling in CRC
      lines depending on the culture mode as we incubated HCT116 and HT29 cells with
      anti-FasR agonistic antibodies. It appeared to act in a line-dependent and
      culture mode-dependent manner and influenced some particular features of CSCs
      such as spherogenicity, proliferation and phenotype. Additionally, the analysis
      of mRNA level showed that disease progression is associated with significantly
      increased expression of FasR and/or FasL. In conclusion, our observation seems to
      confirm that spherical model of cancer lines is more reliable for some
      sophisticated analysis because of their greater resemblance to the CSCs from
      human CRC samples in comparison to commonly used adherent cells, at least
      according to aspects of their biology analyzed in this study. That can be
      extended to the resemblance of in vitro sphere forming conditions to the in vivo
      environment. However, the greatest difference concerns the level of apoptosis,
      thus, this issue require further experiments.

PMID- 28766683
TI  - Pristimerin effectively inhibits the malignant phenotypes of uveal melanoma cells
      by targeting NF-kappaB pathway.
AB  - Uveal melanoma (UM) is a highly aggressive intraocular malignancy that lacks any
      effective targeted-therapy. Neither survival nor prognosis has been improved for
      the past decades in patients with metastatic UM. NF-kappaB pathway is reported to
      be abnormally activated in UM. However, the role of NF-kappaB pathway as a
      potential therapeutical target in UM remains unclear. Here, the effect of
      pristimerin, a potent inhibitor of NF-kappaB pathway, on UM cells in terms of
      growth, apoptosis, motility, invasion and cancer stem-like cells (CSCs) was
      evaluated in vitro. We showed that pristimerin suppressed tumor necrosis factor
      alpha (TNFalpha)-induced IkappaBalpha phosphorylation, translocation of p65, and
      expression of NF-kappaB-dependent genes. Moreover, pristimerin decreased cell
      viability and clonogenic ability of UM cells. A synergistic effect was observed
      in the treatment of pristimerin combined with vinblastine, a frontline
      therapeutic agent, in UM. Pristimerin led to a significant increase in the
      Annexin V+ cell population as measured by flow cytometry. We also observed that
      pristimerin impaired the abilities of migration and invasion in UM cells.
      Furthermore, pristimerin eliminated the ALDH+ cells and weakened serial re
      plating ability of melanosphere. Collectively, pristimerin shows remarkable
      anticancer activities in UM cells through inactivating NF-kappaB pathway,
      revealing that pristimerin may be a promising therapeutic agent in UM.

PMID- 28766684
TI  - Epigallocatechin-3-gallate promotes all-trans retinoic acid-induced maturation of
      acute promyelocytic leukemia cells via PTEN.
AB  - Acute promyelocytic leukemia (APL) is a distinctive subtype of acute myeloid
      leukemia (AML) in which the hybrid protein promyelocytic leukemia
      protein/retinoic acid receptor alpha (PML/RARalpha) acts as a transcriptional
      repressor impairing the expression of genes that are critical to myeloid cell
      mutation. We aimed at explaining the molecular mechanism of green tea polyphenol
      epigallocatechin-3-gallate (EGCG) enhancement of ATRA-induced APL cell line
      differentiation. Tumor suppressor phosphatase and tensin homolog (PTEN) was found
      downregulated in NB4 cells and rescued by proteases inhibitor MG132. A
      significant increase of PTEN levels was found in NB4, HL-60 and THP-1 cells upon
      ATRA combined with EGCG treatment, paralleled by increased myeloid
      differentiation marker CD11b. EGCG in synergy with ATRA promote degradation of
      PML/RARalpha and restores PML expression, and increase the level of nuclear PTEN.
      Pretreatment of PTEN inhibitor SF1670 enhances the PI3K signaling pathway and
      represses NB4 cell differentiation. Moreover, the induction of PTEN attenuated
      the Akt phosphorylation levels, pretreatment of PI3K inhibitor LY294002 in NB4
      cells, significantly augmented the cell differentiation and increased the
      expression of PTEN. These results therefore indicate that EGCG targets
      PML/RARalpha oncoprotein for degradation and potentiates differentiation of
      promyelocytic leukemia cells in combination with ATRA via PTEN.

PMID- 28766685
TI  - Salinomycin's potential to eliminate glioblastoma stem cells and treat
      glioblastoma multiforme (Review).
AB  - Glioblastoma multiforme (GBM) is the most common and deadliest form of primary
      brain tumor. Despite treatment with surgery, radiotherapy, and chemotherapy with
      the drug temozolomide, the expected survival after diagnosis remains low. The
      median survival is only 14.6 months and the two-year survival is a mere 30%. One
      reason for this is the heterogeneity of GBM including the presence of
      glioblastoma cancer stem cells (GSCs). GSCs are a subset of cells with the unique
      ability to proliferate, differentiate, and create tumors. GSCs are resistant to
      chemotherapy and radiation and thought to play an important role in recurrence.
      In order to effectively treat GBM, a drug must be identified that can kill GSCs.
      The ionophore salinomycin has been shown to kill cancer stem cells and is
      therefore a promising future treatment for GBM. This study focuses on
      salinomycin's potential to treat GBM including its ability to reduce the CSC
      population, its toxicity to normal brain cells, its mechanism of action, and its
      potential for combination treatment.

PMID- 28766686
TI  - Benzyl isothiocyanate and phenethyl isothiocyanate inhibit murine melanoma B16F10
      cell migration and invasion in vitro.
AB  - Benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC) have been
      demonstrated to induce anticancer function in many human cancer cells and also
      inhibit cancer cell migration and invasion. However, there are no studies that
      show BITC and PEITC to inhibit cell migration and invasion in mouse melanoma
      B16F10 cells. In this study, we investigated anti-metastasis effects of BITC and
      PEITC in melanoma cancer cells in vitro. Under sub-lethal concentrations (from 1,
      2.5 up to 5 uM), BITC and PEITC significantly inhibited cell mobility, migration
      and invasion nature of B16F10 cells. Gelatin zymography assay also showed that
      BITC and PEITC inhibited matrix metalloproteinase-2 (MMP-2) activity in B16F10
      cells. PEITC reduced MAPK signaling associated proteins such as p-ERK1/2, p-p38
      and p-JNK1/2 but BITC increased those MAPK signaling associated proteins. BITC
      and PEITC both suppressed the expression of RhoA, Ras, and SOS-1, however, PEITC
      increased FAK and GRB2 but BITC increased FAK at 48 h. Furthermore, PEITC
      decreased the expression of MMP-2 and tissue inhibitors of matrix
      metalloproteinases (TIMP) but BITC increased them. PEITC inhibited NF-kappaB
      protein levels and DNA binding which was confirmed by electrophoretic mobility
      shift (EMSA) assay. Based on these observations, we suggest that BITC and PEITC
      can be used in anti-metastasis of melanoma cells in the future.

PMID- 28766687
TI  - Downregulation of BRD4 inhibits gallbladder cancer proliferation and metastasis
      and induces apoptosis via PI3K/AKT pathway.
AB  - Bromodomain containing protein 4 (BRD4) has been demonstrated to play a critical
      role in tumor progression. However, the expression and function of BRD4 in
      gallbladder cancer (GBC) are still unknown. In this study, we report that BRD4
      expression level was significantly upregulated in GBC tissues and GBC cell lines.
      We explored the correlation between BRD4 levels and clinicopathological data of
      GBC patients. The high expression level of BRD4 was notably correlated with the
      poor prognosis of GBC patients. Knockdown of BRD4 suppressed proliferation and
      migration in NOZ and EH-GB1 cells. The depletion of BRD4 in GBC cell lines
      resulted in obvious cell apoptosis and downregulated the expression levels of Bcl
      2, p-PI3K and p-AKT. In vivo, tumor volumes of nude mice were significantly
      decreased in BRD4 silenced group. Our data suggested that downregulation of BRD4
      in GBC cells induced apoptosis by PI3K/AKT pathway. Inhibition of BRD4 expression
      may be a novel therapeutic strategy for patients with GBC.

PMID- 28766689
TI  - Nicotine induces TIPE2 upregulation and Stat3 phosphorylation contributes to
      cholinergic anti-inflammatory effect.
AB  - Cholinergic anti-inflammatory pathway has therapeutic effect on inflammation
      associated diseases. However, the exact mechanism of nicotine-mediated anti
      inflammatory effect is still unclear. TIPE2, a new member of tumor necrosis
      factor-alpha-induced protein-8 family, is a negative regulator of immune
      homeostasis. However, the roles of TIPE2 in cholinergic anti-inflammatory effect
      are still uncertain. Here, we demonstrated that nicotine exerts its anti
      inflammatory effect by TIPE2 upregulation and phosphorylated stat3 mediated the
      inhibition of NF-kappaB activation, which was supported by the following
      evidence: firstly, both nicotine and TIPE2 inhibit pro-inflammatory cytokine
      release via NF-kappaB inactivation. Secondly, nicotine upregulates TIPE2
      expression via alpha7 nicotinic acetylcholine receptor. Moreover, the enhancement
      of stat3 phosphorylation and decrease of LPS-induced p65 translocation were
      achieved by nicotine treatment. Importantly, nicotine treatment augments the
      interaction of phosphorylated stat3 and p65, indicating that the inhibitory
      effect of nicotine on NF-kappaB activation was mediated with protein-protein
      interactions. Hence, this study revealed that TIPE2 upregulation and stat3
      phosphorylation contribute to nicotine-mediated anti-inflammation effect,
      indicating that TIPE2 and stat3 might be potential molecules for dealing with
      inflammation-associated diseases.

PMID- 28766688
TI  - Stathmin1 expression is associated with aggressive phenotypes and cancer stem
      cell marker expression in breast cancer patients.
AB  - Stathmin1 (STMN1) regulates progression in various cancers. The present study
      aimed to determine the relationship between STMN1 expression and several cancer
      related markers in breast cancer. Using immunohistochemistry, we evaluated STMN1,
      estrogen receptor, progesterone receptor, human epidermal growth factor receptor
      2, Ki-67, epidermal growth factor receptor (EGFR), CK5/6, CD44, CD24, aldehyde
      dehydrogenase 1, E-cadherin, epithelial cell adhesion molecule, and vimentin in
      237 breast cancer patients and the clinical significance of STMN1. STMN1
      expression was evaluated in 51 breast cancer cell lines, and the prognostic value
      of STMN1 was calculated. Higher STMN1 expression was detected in cancer tissues
      and was predominantly localized in the cytoplasm. High STMN1 expression was
      associated with the triple negative subtype, nuclear grade progression, high
      expression of Ki-67, EGFR, CK5/6, E-cadherin and high CD44/low CD24. According to
      gene expression-based outcome for breast cancer online and the Kaplan-Meier
      plotter, STMN1 expression was higher in basal-type cell lines than in luminal
      type cell lines, and overall survival and post-progression survival in the high
      STMN1 expression breast cancer patients were shorter than in low STMN1 expression
      patients. High STMN1 expression is a possible marker of breast cancer
      aggressiveness in association with proliferation, phenotype and cancer stem cell
      type.

PMID- 28766691
TI  - Risk factors for peripheral nerve injuries following neuraxial labour analgesia:
      a nested case-control study.
AB  - BACKGROUND: Post-partum lower extremity motor and sensory dysfunctions occur in
      0.1-9.20/00 of deliveries. While macrosomia, lithotomy position and forceps use
      are well-identified causes of peripheral nerve injuries, additional contributors
      such as patient condition and anaesthesia care may also have to be considered.
      METHODS: We performed a case-control study nested in a cohort of 19,840 patients
      having neuraxial anaesthesia for childbirth. Cases were all patients who
      developed motor or sensory dysfunction of lower extremities in the post-partum
      period. These were compared, using Chi-square, Fisher's exact test, logistic
      regression and time series, to a random sample of controls without any
      neurological symptoms or injury. RESULTS: We identified 19 (0.960/00) patients
      with peripheral nerve injuries of which 15 (0.760/00) were likely associated with
      obstetrical care. In four additional cases (0.200/00), a nerve root injury due to
      the Tuohy needle was suspected. Univariate risk factors were: a gestational age
      >= 41 weeks, Odds Ratio (OR) 3.8; 95% CI: 1.1-13.1, late initiation of neuraxial
      anaesthesia OR 8.2; 95% CI: 1.8-37.9, a repeated anaesthetic procedure OR 2.8;
      95% CI: 1.0-7.8, assisted delivery with forceps OR 9.8; 95% CI: 1.2-114.1 and
      newborn birth weight > 3.5 kg with an OR 6.8; 95% CI: 2.0-22.5. CONCLUSION:
      Obstetrical related factors are the most prominent risk associated with
      peripheral nerve injuries. This study highlights however that patient and
      anaesthesia-related factors may also contribute to peripheral nerve injuries.

PMID- 28766690
TI  - Pro-oxidant and pro-apoptotic activity of polyphenol extract from Annurca apple
      and its underlying mechanisms in human breast cancer cells.
AB  - Among nutraceuticals, polyphenols represent the most intriguing and studied class
      of compounds that can be therapeutics for a large spectrum of the most common
      diseases, including cancer. Although polyphenols are well known as potent
      antioxidants, a pro-oxidant effect has been associated with a pro-apoptotic
      function of these compounds in various types of tumor cells. Annurca apple, a
      southern Italian variety, is characterized by an extremely high content of
      polyphenols and displays a stronger antioxidant activity compared with other
      varieties. In the present study we explored the antiproliferative effect of
      Annurca apple polyphenol extract (APE) in human breast cancer MCF-7 cells and we
      investigated the underlying mechanisms. Results showed that at 500 uM catechin
      equivalent (EqC) APE acts as a pro-oxidant increasing thiobarbituric acid
      reactive species cell content of approximately 6-fold more than the untreated
      cells. We found that APE strongly inhibits the proliferation of MCF-7 cells by
      inducing G2/M cell cycle arrest and apoptosis. Immunoblot analysis demonstrated
      that APE treatment increases the levels of p53 and p21, downregulates the
      expression of the cell cycle regulatory protein cyclin D1, and inhibits ERK1/2
      phosphorylation. Moreover, APE treatment caused a marked increase of pro
      apoptotic Bax/Bcl-2 ratio paralleled by caspase-9, -6, -7, and poly(ADP ribose)
      polymerase cleavage. Altogether our data indicate that APE, at elevated
      concentrations, acts as a potent pro-oxidant and antiproliferative agent able to
      downregulate ERK1/2 pathway leading to cell cycle inhibition and apoptosis and
      provides a rationale for its potential use in the development of novel
      therapeutics towards breast cancer.

PMID- 28766692
TI  - Truncal varicose vein diameter and patient-reported outcome measures.
AB  - BACKGROUND: Varicose veins and chronic venous disease are common, and some
      funding bodies ration treatment based on a minimum diameter of the incompetent
      truncal vein. This study assessed the effect of maximum vein diameter on clinical
      status and patient symptoms. METHODS: A prospective observational cohort study of
      patients presenting with symptomatic varicose veins to a tertiary referral public
      hospital vascular clinic between January 2011 and July 2012. Patients underwent
      standardized assessment with venous duplex ultrasonography, and completed
      questionnaires assessing quality of life (QoL) and symptoms (Aberdeen Varicose
      Vein Questionnaire, EuroQol Five Domain QoL assessment and EuroQol visual
      analogue scale). Clinical scores (Venous Clinical Severity Score (VCSS) and
      Clinical Etiologic Anatomic Pathophysiologic (CEAP) class) were also calculated.
      Regression analysis was used to investigate the relationship between QoL,
      symptoms and vein diameter. RESULTS: Some 330 patients were assessed before
      surgery. The median maximum vein diameter was 7.0 (i.q.r. 5.3-9.2) mm overall,
      7.9 (6.0-9.8) mm for great saphenous vein and 6.0 (5.2-8.9) mm for small
      saphenous vein. In linear regression analysis, vein diameter was shown to have a
      significant association with VCSS (P = 0.041). For every 1-mm increase in vein
      diameter, there was a 2.75-fold increase in risk of being in CEAP class C4
      compared with C2. No other QoL or symptom measures were related to vein diameter.
      CONCLUSION: Incompetent truncal vein diameter was associated with increasing
      VCSS, but not a variety of other varicose vein disease-specific and generic
      patient-reported outcome measures.

PMID- 28766693
TI  - Testing the niche-breadth-range-size hypothesis: habitat specialization vs.
      performance in Australian alpine daisies.
AB  - Relatively common species within a clade are expected to perform well across a
      wider range of conditions than their rarer relatives, yet experimental tests of
      this "niche-breadth-range-size" hypothesis remain surprisingly scarce. Rarity may
      arise due to trade-offs between specialization and performance across a wide
      range of environments. Here we use common garden and reciprocal transplant
      experiments to test the niche-breadth-range-size hypothesis, focusing on four
      common and three rare endemic alpine daisies (Brachyscome spp.) from the
      Australian Alps. We used three experimental contexts: (1) alpine reciprocal
      seedling experiment, a test of seedling survival and growth in three alpine
      habitat types differing in environmental quality and species diversity; (2) warm
      environment common garden, a test of whether common daisy species have higher
      growth rates and phenotypic plasticity, assessed in a common garden in a warmer
      climate and run simultaneously with experiment 1; and (3) alpine reciprocal seed
      experiment, a test of seed germination capacity and viability in the same three
      alpine habitat types as in experiment 1. In the alpine reciprocal seedling
      experiment, survival of all species was highest in the open heathland habitat
      where overall plant diversity is high, suggesting a general, positive response to
      a relatively productive, low-stress environment. We found only partial support
      for higher survival of rare species in their habitats of origin. In the warm
      environment common garden, three common daisies exhibited greater growth and
      biomass than two rare species, but the other rare species performed as well as
      the common species. In the alpine reciprocal seed experiment, common daisies
      exhibited higher germination across most habitats, but rare species maintained a
      higher proportion of viable seed in all conditions, suggesting different life
      history strategies. These results indicate that some but not all rare, alpine
      endemics exhibit stress tolerance at the cost of reduced growth rates in low
      stress environments compared to common species. Finally, these findings suggest
      the seed stage is important in the persistence of rare species, and they provide
      only weak support at the seedling stage for the niche-breadth-range-size
      hypothesis.

PMID- 28766694
TI  - Musicogenic reflex seizures in epilepsy with glutamic acid decarbocylase
      antibodies.
AB  - BACKGROUND: Musicogenic reflex seizures (MRS) are a rare form of seizures
      described in patients with temporal lobe epilepsy (TLE), mainly of unknown
      etiology. Epilepsy with antibodies against glutamic acid decarboxylase (GAD-ab)
      is a form of autoimmune epilepsy for which no specific semiology has been
      described. AIM OF THE STUDY: To retrospectively review the incidence of MRS in
      the general epileptic population and in the series of patients with epilepsy and
      GAD-ab and to describe its clinical and paraclinical characteristics. METHODS:
      Patients recorded between January 2010 and January 2016 in the Database of
      Bellvitge Hospital Epilepsy Unit were reviewed. RESULTS: From a group of 1510
      epileptic patients, three reported MRS (0.0019%) (two patients with epilepsy and
      GAD-ab and one patient with cryptogenic TLE). The incidence of MRS in patients
      with epilepsy and GAD-ab was 2 of 22 (9%). Both patients had a normal magnetic
      resonance Imaging (MRI), but FDG-PET showed medial temporal lobe hypometabolism
      (unilateral or bilateral) in both and also in the insula in one of them. MRS
      (recorded via video-EEG[electroencephalography] in one patient) arose from the
      right temporal lobe. CONCLUSIONS: MRS may be a distinctive seizure type in
      patients with epilepsy and antiGADab. Determination of GAD-ab should be carried
      out in all cases of MRS, even those with normal structural MRI.

PMID- 28766695
TI  - Prevention of Alzheimer's Disease: Lessons Learned and Applied.
AB  - Alzheimer's disease (AD) affects more than 5 million Americans, with substantial
      consequences for individuals with AD, families, and society in terms of
      morbidity, mortality, and healthcare costs. With disease-modifying treatment
      trials unsuccessful at the present time and only medications to treat symptoms
      available, an emerging approach is prevention. Advances in diagnostic criteria,
      biomarker development, and greater understanding of the biophysiological basis of
      AD make these initiatives feasible. Ongoing pharmacological trials using anti
      amyloid therapies are underway in sporadic and genetic forms of AD, although a
      large number of modifiable risk factors for AD have been identified in
      observational studies, many of which do not appear to exert effects through
      amyloid or tau. This suggests that prevention studies focusing on risk reduction
      and lifestyle modification may offer additional benefits. Rather than relying
      solely on large-sample, long-duration, randomized clinical trial designs, a
      precision medicine approach using N-of-1 trials may provide more-rapid
      information on whether personalized prevention plans can improve person-centered
      outcomes. Because there appear to be multiple pathways to developing AD, there
      may also be multiple ways to prevent or delay the onset of AD. Even if these
      precision approaches alone are not successful in preventing AD, they may greatly
      improve the likelihood of amyloid- or tau-specific therapies to reach their
      endpoints by reducing comorbidities. Keeping this in mind, dementia may be a
      disorder that develops over a lifetime, with individualized ways to build a
      better brain as we age.

PMID- 28766696
TI  - Serial perioperative cell-free DNA levels in donors and recipients undergoing
      living donor liver transplantation.
AB  - BACKGROUND: Effect of anaesthesia and surgery on cell-free DNA (cfDNA) is not
      known. Given that surgical stress augments inflammation and injury, we
      hypothesized that levels of cfDNA will fluctuate during perioperative period.
      Therefore, in this study serial perioperative cfDNA concentration was measured in
      donors and recipients undergoing living donor liver transplantation (LDLT).
      METHODS: Baseline, post-induction, intraoperative and post-operative plasma cfDNA
      levels were evaluated in 21 donors and recipients each, by Sytox green method. In
      addition, qPCR was performed in a subset of samples. RESULTS: Baseline cfDNA
      levels were higher in recipients (37.62 ng/ml) than in donors (25.49 ng/ml). A
      decrease in cfDNA was observed following anaesthesia induction in both recipients
      (11.90 ng/ml) and donors (10.75 ng/ml). When the kinetics of the cfDNA was
      monitored further, an increase was noted intraoperatively in donors (46.18 ng/ml)
      and recipients (anhepatic phase: 56.25 ng/ml, reperfusion phase: 54.36 ng/ml).
      cfDNA levels remained high post-operatively. One recipient who developed post
      operative sepsis had the highest cfDNA level (94.72 ng/ml). CONCLUSION: Plasma
      cfDNA levels are high in recipients indicative of liver injury. Lower cfDNA
      levels following induction may be attributed to the subduing effect of
      anaesthetic agents on cell death. High cfDNA levels seen in intra- and post
      operative phases reflect cellular trauma and inflammation. This similar pattern
      of fluctuation of cfDNA level in donors and recipients is suggestive of its
      possible utility as a surgical stress marker. In addition, comparable cfDNA
      levels in anhepatic and reperfusion phase reflect less ischemia reperfusion
      injury during LDLT.

PMID- 28766697
TI  - Can snowshoe hares control treeline expansions?
AB  - Treelines in Alaska are advancing in elevation and latitude because of climate
      warming, which is expanding the habitat available for boreal wildlife species,
      including snowshoe hares (Lepus americanus). Snowshoe hares are already present
      in tall shrub communities beyond treeline and are the main browser of white
      spruce (Picea glauca), the dominant tree species at treeline in Alaska. We
      investigated the processes involved in a "snowshoe hare filter" to white spruce
      establishment near treeline in Denali National Park, Alaska, USA. We modeled the
      pattern of spruce establishment from 1970 to 2009 and found that fewer spruce
      established during periods of high hare abundance. Multiple factors interact to
      influence browsing of spruce, including the hare cycle, snow depth and the
      characteristics of surrounding vegetation. Hares are abundant at treeline and may
      exclude spruce from otherwise optimal establishment sites, particularly
      floodplain locations with closed shrub canopies. The expansion of white spruce
      treeline in response to warming climate will be strongly modified by the spatial
      and temporal dynamics of the snowshoe hare filter.

PMID- 28766698
TI  - Allocation, not male resistance, increases male frequency during epidemics: a
      case study in facultatively sexual hosts.
AB  - Why do natural populations vary in the frequency of sexual reproduction? Virulent
      parasites may help explain why sex is favored during disease epidemics. To
      illustrate, we show a higher frequency of males and sexually produced offspring
      in natural populations of a facultative parthenogenetic host during fungal
      epidemics. In a multi-year survey of 32 lakes, the frequency of males (an index
      of sex) was higher in populations of zooplankton hosts with larger epidemics. A
      lake mesocosm experiment established causality: experimental epidemics produced a
      higher frequency of males relative to disease-free controls. One common
      explanation for such a pattern involves Red Queen (RQ) dynamics. However, this
      particular system lacks key genetic specificity mechanisms required for the RQ,
      so we evaluated two other hypotheses. First, individual females, when stressed by
      infection, could increase production of male offspring vs. female offspring (a
      tenant of the "Abandon Ship" theory). Data from a life table experiment supports
      this mechanism. Second, higher male frequency during epidemics could reflect a
      purely demographic process (illustrated with a demographic model): males could
      resist infection more than females (via size-based differences in resistance and
      mortality). However, we found no support for this resistance mechanism. A size
      based model of resistance, parameterized with data, revealed why: higher male
      susceptibility negated the lower exposure (a size-based advantage) of males.
      These results suggest that parasite-mediated increases in allocation to sex by
      individual females, rather than male resistance, increased the frequency of sex
      during larger disease epidemics.

PMID- 28766699
TI  - A method of factor analysis for shape coordinates.
AB  - Currently the most common reporting style for a geometric morphometric (GMM)
      analysis of anthropological data begins with the principal components of the
      shape coordinates to which the original landmark data have been converted. But
      this focus often frustrates the organismal biologist, mainly because principal
      component analysis (PCA) is not aimed at scientific interpretability of the
      loading patterns actually uncovered. The difficulty of making biological sense of
      a PCA is heightened by aspects of the shape coordinate setting that further
      diverge from our intuitive expectations of how morphometric measurements ought to
      combine. More than 50 years ago one of our sister disciplines, psychometrics,
      managed to build an algorithmic route from principal component analysis to
      scientific understanding via the toolkit generally known as factor analysis. This
      article introduces a modification of one standard factor-analysis approach, Henry
      Kaiser's varimax rotation of 1958, that accommodates two of the major differences
      between the GMM context and the psychometric context for these approaches: the
      coexistence of "general" and "special" factors of form as adumbrated by Sewall
      Wright, and the typical loglinearity of partial warp variance as a function of
      bending energy. I briefly explain the history of principal components in
      biometrics and the contrast with factor analysis, introduce the modified varimax
      algorithm I am recommending, and work three examples that are reanalyses of
      previously published cranial data sets. A closing discussion emphasizes the
      desirability of superseding PCA by algorithms aimed at anthropological
      understanding rather than classification or ordination.

PMID- 28766700
TI  - Predicting coexistence in species with continuous ontogenetic niche shifts and
      competitive asymmetry.
AB  - A longstanding problem in ecology is whether structured life cycles impede or
      facilitate coexistence between species. Theory based on populations with only two
      discrete stages in the life-cycle indicates that for two species to coexist, at
      least one must shift its niche between stages and each species must be a better
      competitor in one of the niches. However, in many cases, niche shifts are
      associated with changes in an underlying continuous trait like body size and we
      have few predictions concerning conditions for coexistence for such a widespread
      form of ontogenetic development. We develop a framework for analyzing species
      coexistence based on Integral Projection Models (IPMs) that incorporates
      continuous ontogenetic changes in both the resource niche and competitive
      ability. We parameterize the model using experimental data from Trinidadian
      guppies and show how niche shifts and competitive symmetries impact species
      coexistence. Overall, our results show that the effects of competition on fitness
      depend upon trait-mediated niche-separation, trait-mediated competitive asymmetry
      in the part of the niche that is shared across body sizes, and the sensitivity of
      fitness to body size. Interactions among these processes generate multiple routes
      to coexistence. We discuss how our modeling framework expands results from two
      stage models to mutli-stage or continuous stage models and allows for deriving
      predictions that can be tested in populations displaying continuous changes in
      niche use and competitive ability.

PMID- 28766701
TI  - Rationale for an adjunctive therapy with fenofibrate in pharmacoresistant
      nocturnal frontal lobe epilepsy.
AB  - OBJECTIVE: Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial
      epilepsy with a family history in about 25% of cases, with autosomal dominant
      inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs
      are effective in about 55% of patients, whereas the rest remains refractory. One
      of the key pathogenetic mechanisms is a gain of function of neuronal nicotinic
      acetylcholine receptors (nAChRs) containing the mutated alpha4 or beta2 subunits.
      Fenofibrate, a common lipid-regulating drug, is an agonist at peroxisome
      proliferator-activated receptor alpha (PPARalpha) that is a ligand-activated
      transcription factor, which negatively modulates the function of beta2-containing
      nAChR. To test clinical efficacy of adjunctive therapy with fenofibrate in
      pharmacoresistant ADNFLE?NFLE patients, we first demonstrated the effectiveness
      of fenofibrate in a mutated mouse model displaying both disease genotype and
      phenotype. METHODS: We first tested the efficacy of fenofibrate in transgenic
      mice carrying the mutation in the alpha4-nAChR subunit (Chrna4S252F) homologous
      to that found in humans. Subsequently, an add-on protocol was implemented in a
      clinical setting and fenofibrate was administered to pharmacoresistant NFLE
      patients. RESULTS: Here, we show that a chronic fenofibrate diet markedly reduced
      the frequency of large inhibitory postsynaptic currents (IPSCs) recorded from
      cortical pyramidal neurons in Chrna4S252F mice, and prevented nicotine-induced
      increase of IPSC frequency. Moreover, fenofibrate abolished differences between
      genotypes in the frequency of sleep-related movements observed under basal
      conditions. Patients affected by NFLE, nonresponders to traditional therapy, by
      means of adjunctive therapy with fenofibrate displayed a reduction of seizure
      frequency. Furthermore, digital video-polysomnographic recordings acquired in
      NFLE subjects after 6 months of adjunctive fenofibrate substantiated the
      significant effects on control of motor-behavioral seizures. SIGNIFICANCE: Our
      preclinical and clinical studies suggest PPARalpha as a novel disease-modifying
      target for antiepileptic drugs due to its ability to regulate dysfunctional
      nAChRs.

PMID- 28766702
TI  - The type IV secretion system core component VirB8 interacts via the beta1-strand
      with VirB10.
AB  - In this work, we provide evidence for the interactions between VirB8 and VirB10,
      two core components of the type IV secretion system (T4SS). Using nuclear
      magnetic resonance experiments, we identified residues on the beta1-strand of
      Brucella VirB8 that undergo chemical shift changes in the presence of VirB10.
      Bacterial two-hybrid experiments confirm the importance of the beta1-strand,
      whereas phage display experiments suggest that the alpha2-helix of VirB8 may also
      contribute to the interaction with VirB10. Conjugation assays using the VirB8
      homolog TraE as a model show that several residues on the beta1-strand of TraE
      are important for T4SS function. Together, our results suggest that the beta1
      strand of VirB8-like proteins is essential for their interaction with VirB10 in
      the T4SS complex.

PMID- 28766703
TI  - Temperamental Anger and Effortful Control, Teacher-Child Conflict, and
      Externalizing Behavior Across the Elementary School Years.
AB  - This study examined teacher-child conflict as a possible mediator of the effects
      of temperamental anger and effortful control on subsequent externalizing
      behavior. Reciprocal influences between teacher-child conflict and externalizing
      behavior were also examined. Participants were 1,152 children (49% female; 81.6%
      non-Hispanic White) from the Study of Early Child Care and Youth Development.
      Multivariate growth curve modeling revealed that greater effortful control at age
      54 months indirectly predicted lower levels of, and subsequent changes in,
      externalizing behavior from kindergarten to Grade 6 through reduced teacher-child
      conflict. An alternative model, in which greater effortful control predicted
      lower teacher-child conflict through lower externalizing behavior, received less
      support. Within persons, greater-than-expected teacher-child conflict predicted
      greater-than-expected teacher-reported externalizing behavior concurrently and
      over time.

PMID- 28766704
TI  - A new era for cervical screening in Australia: Watch this space!

PMID- 28766705
TI  - Grover's disease in a patient with pemphigus vulgaris.

PMID- 28766706
TI  - Warming effects on permafrost ecosystem carbon fluxes associated with plant
      nutrients.
AB  - Large uncertainties exist in carbon (C)-climate feedback in permafrost regions,
      partly due to an insufficient understanding of warming effects on nutrient
      availabilities and their subsequent impacts on vegetation C sequestration.
      Although a warming climate may promote a substantial release of soil C to the
      atmosphere, a warming-induced increase in soil nutrient availability may enhance
      plant productivity, thus offsetting C loss from microbial respiration. Here, we
      present evidence that the positive temperature effect on carbon dioxide (CO2 )
      fluxes may be weakened by reduced plant nitrogen (N) and phosphorous (P)
      concentrations in a Tibetan permafrost ecosystem. Although experimental warming
      initially enhanced ecosystem CO2 uptake, the increased rate disappeared after the
      period of peak plant growth during the early growing season, even though soil
      moisture was not a limiting factor in this swamp meadow ecosystem. We observed
      that warming did not significantly affect soil extractable N or P during the
      period of peak growth, but decreased both N and P concentrations in the leaves of
      dominant plant species, likely caused by accelerated plant senescence in the
      warmed plots. The attenuated warming effect on CO2 assimilation during the late
      growing season was associated with lowered leaf N and P concentrations. These
      findings suggest that warming-mediated nutrient changes may not always benefit
      ecosystem C uptake in permafrost regions, making our ability to predict the C
      balance in these warming-sensitive ecosystems more challenging than previously
      thought.

PMID- 28766707
TI  - Taking Root: a grounded theory on evidence-based nursing implementation in China.
AB  - BACKGROUND: Evidence-based nursing is widely recognized as the critical
      foundation for quality care. AIM: To develop a middle-range theory on the process
      of evidence-based nursing implementation in Chinese context. METHODS: A grounded
      theory study using unstructured in-depth individual interviews was conducted with
      56 participants who were involved in 24 evidence-based nursing implementation
      projects in Mainland China from September 2015 to September 2016. RESULTS: A
      middle-range grounded theory of 'Taking Root' was developed. The theory describes
      the evidence implementation process consisting of four components (driving
      forces, process, outcome, sustainment/regression), three approaches (top-down,
      bottom-up and outside-in), four implementation strategies (patient-centred,
      nurses at the heart of change, reaching agreement, collaboration) and two
      patterns (transformational and adaptive implementation). LIMITATIONS: Certain
      perspectives may have not been captured, as the retrospective nature of the
      interviewing technique did not allow for 'real-time' assessment of the actual
      implementation process. The transferability of the findings requires further
      exploration as few participants with negative experiences were recruited.
      CONCLUSION: This is the first study that explored evidence-based implementation
      process, strategies, approaches and patterns in the Chinese nursing practice
      context to inform international nursing and health policymaking. The theory of
      Taking Root described various approaches to evidence implementation and how the
      implementation can be transformational for the nurses and the setting in which
      they work. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nursing educators,
      managers and researchers should work together to improve nurses' readiness for
      evidence implementation. Healthcare systems need to optimize internal mechanisms
      and external collaborations to promote nursing practice in line with evidence and
      achieve clinical outcomes and sustainability.

PMID- 28766708
TI  - Authors' response.

PMID- 28766709
TI  - Compensated surrogacy in Australia.

PMID- 28766711
TI  - Sex hormones, receptors and modulators.

PMID- 28766710
TI  - Response to 'Term breech delivery: Is recommending vaginal birth a breach of best
      practice?'

PMID- 28766712
TI  - Can degradation products released from dental implants affect peri-implant
      tissues?
AB  - This study aimed to assess the literature available on the effects, on peri
      implant tissues, of degradation products released from dental implants as a
      consequence of therapeutic treatment for peri-implantitis and/or of wear
      corrosion of titanium. A literature review of the PubMed medline database was
      performed up to December 31, 2016. The following search terms were used:
      "titanium wear and dental implant"; "titanium corrosion and dental implant"; "bio
      tribocorrosion"; "peri-implantitis"; "treatment of peri-implantitis"; "titanium
      particles release and dental implant"; and "titanium ion release and dental
      implant". The keywords were applied to the database in different combinations
      without limits of time period or type of work. In addition, the reference lists
      of relevant articles were searched for further studies. Seventy-nine relevant
      scientific articles on the topic were retrieved. The results showed that pro
      inflammatory cytokines, infiltration of inflammatory response cells and
      activation of the osteoclasts activity are stimulated in peri-implant tissues in
      the presence of metal particles and ions. Moreover, degenerative changes were
      reported in macrophages and neutrophils that phagocytosed titanium
      microparticles, and mutations occurred in human cells cultured in medium
      containing titanium-based nanoparticles. Debris released from the degradation of
      dental implants has cytotoxic and genotoxic potential for peri-implant tissues.
      Thus, the amount and physicochemical properties of the degradation products
      determine the magnitude of the detrimental effect on peri-implant tissues.

PMID- 28766713
TI  - Comparison between Temperature Gradient Gel Electrophoresis of Bacterial 16S rDNA
      and Diatom Test for Diagnosis of Drowning.
AB  - When a body is discovered in water, it is difficult to conclude whether the cause
      of death was drowning, even today. Although diatom testing by the digestive
      method is classical, we hypothesized that aquatic bacteria, as well as diatoms,
      might be detected in drowned bodies, and conducted temperature gradient gel
      electrophoresis (TGGE)-targeting 16S rDNA. DNA was extracted from the site water,
      and from heart blood and liver samples from 27 bodies concluded as drowning
      deaths by autopsy and subjected to TGGE after amplification of 16S rDNA by
      polymerase chain reaction. We observed whether the feature point of each 16S rDNA
      from the site water and blood or liver samples matched. Considerably higher
      correspondence was observed in drowned bodies, and the rate was higher than that
      achieved with the digestive method. Moreover, TGGE is safer than the digestive
      method. Our study suggests that this method can aid diagnosis of drowning.

PMID- 28766714
TI  - Psychophysiological Responses of People with Psychopathic Tendencies to the
      Concealed Information Test.
AB  - This study was designed to investigate differences in psychophysiological
      responses among individuals with psychopathic tendencies. A total 40 students
      were participated and were divided into two groups based on Levenson Self-Report
      Psychopathy Scale (LSRP) scores: a high psychopathic tendency group selected from
      the top 5% of LSRP scores, and a low psychopathic tendency group selected from
      the bottom 5% of LSRP scores. All participants were instructed to perform a mock
      crime and complete the concealed information test (CIT). Results indicate that
      significant differences between crime-relevant questions and irrelevant questions
      were observed for respiration line length and skin conductance response in both
      groups, but heart rate did not significantly differ between groups. There were no
      differences in psychophysiological responses between the groups. In conclusion,
      CIT was found to be an effective method for detecting crime-relevant information
      in individuals with psychopathic tendencies.

PMID- 28766715
TI  - Hypertonic NaCl versus osmotic stimuli: distinct OVLT neurones can sense the
      difference to control sympathetic outflow and blood pressure.

PMID- 28766716
TI  - Sequential segmental analysis of the crocodilian heart.
AB  - Differences between hearts of crocodilians and those of mammals and birds are
      only partly understood because there is no standardised approach and terminology
      for describing cardiac structure. Whereas most reptiles have an undivided
      ventricle, crocodilians have a fully septated ventricle. Their hearts, therefore,
      are more readily comparable with the hearts of mammals and birds. Here, we
      describe the heart of a crocodile (Crocodylus noliticus). We use the versatile
      sequential segmental approach to analysis, juxtaposing several key views of the
      crocodilian heart to the comparable views of human hearts. In crocodiles, the
      atrial and ventricular septums are complete but, unlike in placental mammals, the
      atrial septum is without an oval fossa. The myocardial component of the
      crocodilian ventricular septum dominates, but the membranous septum likely makes
      up a greater proportion than in any mammal. In the crocodile, the aortic trunk
      takes its origin from the left ventricle and is not wedged between the
      atrioventricular junctions. Consequently, there is a common atrioventricular
      junction, albeit with separate right and left atrioventricular valvar orifices.
      As in mammals, nonetheless, the crocodilian left atrioventricular valvar orifice
      is cranial to the right atrioventricular valvar orifice. By applying a method of
      analysis and terminology usually restricted to the human heart, we build from the
      considerable existing literature to show neglected and overlooked shared
      features, such as the offset between the left and right atrioventricular valvar
      orifices. Such commonalities are surprising given the substantial evolutionary
      divergence of the archosaur and synapsid lineages, and likely reflect
      evolutionarily shared morphogenetic programmes.

PMID- 28766717
TI  - Unplanned Complex Suicide-A Consideration of Multiple Methods.
AB  - Detailed death investigations are mandatory to find out the exact cause and
      manner in non-natural deaths. In this reference, use of multiple methods in
      suicide poses a challenge for the investigators especially when the choice of
      methods to cause death is unplanned. There is an increased likelihood that doubts
      of homicide are raised in cases of unplanned complex suicides. A case of complex
      suicide is reported where the victim resorted to multiple methods to end his
      life, and what appeared to be an unplanned variant based on the death scene
      investigations. A meticulous crime scene examination, interviews of the victim's
      relatives and other witnesses, and a thorough autopsy are warranted to conclude
      on the cause and manner of death in all such cases.

PMID- 28766718
TI  - Left Ventricular Aneurysm: Sudden Unexpected Deaths in a 29-Year-Old Man.
AB  - Left ventricular aneurysm (LVA) is an abnormal dilated heart structure, either
      congenital or acquired. LVA is a rare cardiac condition with no symptoms in most
      cases, thus occasionally diagnosed during investigations of other diseases. Its
      association with certain cardiac complications and sudden cardiac deaths has been
      reported. However, its role as a cause of sudden unexpected death is rare. The
      author reported a sudden cardiac death in a 29-year-old man with LVA. Without a
      significant coronary artery disease and known etiologies of LVA, such an abnormal
      heart structure in the present case was considered congenital LVA. As no other
      possible mechanisms of death could be identified other than LVA with its
      associated pathologic lesions, mural thrombi, and dilated cardiomegaly, his death
      was attributable to fatal cardiac arrhythmia (most commonly ventricular
      tachycardia) secondary to LVA.

PMID- 28766719
TI  - Control of the depth and rate of breathing: metabolic vs. non-metabolic inputs.

PMID- 28766720
TI  - Molecular characterization of rice arsenic-induced RING finger E3 ligase 2
      (OsAIR2) and its heterogeneous overexpression in Arabidopsis thaliana.
AB  - Arsenic (As) accumulation adversely affects the growth and productivity of plants
      and poses a serious threat to human health and food security. In this study, we
      identified one As-responsive Really Interesting New Gene (RING) E3 ubiquitin
      ligase gene from rice root tissues during As stress. We named it Oryza sativa As
      Induced RING E3 ligase 2 (OsAIR2). Expression of OsAIR2 was induced under various
      abiotic stress conditions, including heat, salt, drought and As exposure. Results
      of an in vitro ubiquitination assay showed that OsAIR2 possesses an E3 ligase
      activity. Within the cell, OsAIR2 was found to be localized to the Golgi
      apparatus. Using yeast two-hybrid (Y2H) assay, the 3-ketoacyl-CoA thiolase (KAT)
      protein was identified as an interaction partner. We found that the O. sativa
      KAT1 (OsKAT1) is localized to the cytosol and peroxisomes. Moreover, in vitro
      pull-down assay verified the physical interaction between OsAIR2 and OsKAT1.
      Interestingly, in vitro ubiquitination assay and in vivo proteasomal degradation
      assay revealed that OsAIR2 ubiquitinates OsKAT1 and promotes the degradation of
      OsKAT1 via the 26S proteasome degradation pathway. Heterogeneous overexpression
      of OsAIR2 in Arabidopsis improved the seed germination and increased the root
      length under arsenate stress conditions. Therefore, these results suggest that
      OsAIR2 may be associated with the plant response to As stress and acts as a
      positive regulator of As stress tolerance.

PMID- 28766721
TI  - Traumatic cutaneous myiasis by Wohlfahrtia magnifica in a stray dog in Italy.

PMID- 28766722
TI  - Fatal Diabetic Ketoacidosis-A Potential Complication of MDMA (Ecstasy) Use.
AB  - A 19-year-old woman with insulin-dependent diabetes mellitus was found dead in
      bed having allegedly recently taken ecstasy and consumed alcohol. At autopsy,
      there were microhemorrhages in the brain with subnuclear vacuolization and
      Armanni-Ebstein changes in renal tubules. Biochemical analyses confirmed diabetic
      ketoacidosis (vitreous glucose-46.5 mmol/L; beta-OH butyrate-13.86 mmol/L.).
      Toxicological analyses of blood showed a low level of 3,4-methylenedioxy
      methamphetamine (MDMA) (0.01 mg/L), with acetone but no alcohol or other common
      drugs. Death was attributed to diabetic ketoacidosis most likely provoked by
      mixed MDMA/alcohol ingestion. Although the use of illicit drugs by young
      individuals with diabetes mellitus is being increasingly recognized, it has been
      noted that there is minimal information about the relationship between drug use
      and acute diabetic complications. Toxicological screening of cases of lethal
      diabetic ketoacidosis in the young may clarify lethal mechanisms in individual
      cases and also help to determine the extent of this problem.

PMID- 28766723
TI  - Comparing transfusion reaction rates for various plasma types: a systematic
      review and meta-analysis/regression.
AB  - BACKGROUND: We estimated rates for common plasma-associated transfusion reactions
      and compared reported rates for various plasma types. STUDY DESIGN AND METHODS:
      We performed a systematic review and meta-analysis of peer-reviewed articles that
      reported plasma transfusion reaction rates. Random-effects pooled rates were
      calculated and compared between plasma types. Meta-regression was used to compare
      various plasma types with regard to their reported plasma transfusion reaction
      rates. RESULTS: Forty-eight studies reported transfusion reaction rates for fresh
      frozen plasma (FFP; mixed-sex and male-only), amotosalen INTERCEPT FFP, methylene
      blue-treated FFP, and solvent/detergent-treated pooled plasma. Random-effects
      pooled average rates for FFP were: allergic reactions, 92/105 units transfused
      (95% confidence interval [CI], 46-184/105 units transfused); febrile nonhemolytic
      transfusion reactions (FNHTRs), 12/105 units transfused (95% CI, 7-22/105 units
      transfused); transfusion-associated circulatory overload (TACO), 6/105 units
      transfused (95% CI, 1-30/105 units transfused); transfusion-related acute lung
      injury (TRALI), 1.8/105 units transfused (95% CI, 1.2-2.7/105 units transfused);
      and anaphylactic reactions, 0.8/105 units transfused (95% CI, 0-45.7/105 units
      transfused). Risk differences between plasma types were not significant for
      allergic reactions, TACO, or anaphylactic reactions. Methylene blue-treated FFP
      led to fewer FNHTRs than FFP (risk difference = -15.3 FNHTRs/105 units
      transfused; 95% CI, -24.7 to -7.1 reactions/105 units transfused); and male-only
      FFP led to fewer cases of TRALI than mixed-sex FFP (risk difference = -0.74
      TRALI/105 units transfused; 95% CI, -2.42 to -0.42 injuries/105 units
      transfused). CONCLUSION: Meta-regression demonstrates that the rate of FNHTRs is
      lower for methylene blue-treated compared with FFP, and the rate of TRALI is
      lower for male-only than for mixed-sex FFP; whereas no significant differences
      are observed between plasma types for allergic reactions, TACO, or anaphylactic
      reactions. Reported transfusion reaction rates suffer from high heterogeneity.

PMID- 28766724
TI  - A methodology based on insecticide impregnated filter paper for monitoring
      resistance to deltamethrin in Triatoma infestans field populations.
AB  - The domiciliary presence of Triatoma infestans (Klug) (Hemiptera: Reduviidae)
      after control interventions was reported in recent years. Toxicological studies
      showed high levels of resistance to pyrethroids suggesting resistance as one of
      the main causes of deficient control. The aim of the present study was to develop
      a protocol to test resistance to deltamethrin in T. infestans collected from the
      field by discriminate concentration. To evaluate field insects, the effect of age
      (early vs. later) and nutritional state (starved vs. fed) on the deltamethrin
      susceptibility of each developmental stage was studied. Topical and insecticide
      impregnated paper bioassays were used. Using the impregnated paper, the
      susceptibility to deltamethrin was not affected by the age of the stadium and the
      nutritional states, and varied with the post-exposure time and with the different
      developmental stages. A discriminant concentration of deltamethrin (0.36% w/v)
      impregnated in filter paper was established for all developmental stages.
      Finally, the methodology and the discriminant concentration were evaluated in the
      laboratory showing high sensitivity in the discrimination of resistance. The
      present study developed a methodology of exposure to insecticide impregnated
      papers and proposes a protocol to test T. infestans in field populations with the
      aim to detect early evolution of resistance to deltamethrin.

PMID- 28766725
TI  - Partial atomic multipoles for internally consistent microelectrostatic
      calculations.
AB  - An extension of the extant microelectrostatic methodologies, based on the concept
      of distributed generalized polarizability matrix derived from the Coupled
      Perturbed Hartree-Fock (CPHF) equations, is proposed for self-consistent
      calculation of charge carrier and charge-transfer (CT) state electrostatic
      energies in molecular solids, including the doped, defected and disordered ones.
      The CPHF equations are solved only once and the generalized molecular
      polarizability they yield enables low cost iterations that mutually adjust the
      molecular electronic distributions and the local electric field in which the
      molecules are immersed. The approach offers a precise picture of molecular charge
      densities, accounting for atomic partial multipoles up to order 2, which allows
      one to reproduce the recently reported large charge-quadrupole contributions to
      CT state energies in low-symmetry local environments. It is particularly well
      suited for repetitive calculations for large clusters (up to 300,000 atoms), and
      may potentially be useful for describing electrostatic solvent effects. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28766726
TI  - A novel 3D-printed phantom insert for 4D PET/CT imaging and simultaneous
      integrated boost radiotherapy.
AB  - PURPOSE: To construct a 3D-printed phantom insert designed to mimic the variable
      PET tracer uptake seen in lung tumor volumes and a matching dosimetric insert to
      be used in simultaneous integrated boost (SIB) phantom studies, and to evaluate
      the design through end-to-end tests. METHODS: A set of phantom inserts was
      designed and manufactured for a realistic representation of gated radiotherapy
      steps from 4D PET/CT scanning to dose delivery. A cylindrical phantom (phi80 *
      120 mm) holds inserts for PET/CT scanning. The novel 3D printed insert dedicated
      to 4D PET/CT mimics high PET tracer uptake in the core and low uptake in the
      periphery. This insert is a variable density porous cylinder (phi44.5 * 70.0 mm),
      ABS-P430 thermoplastic, 3D printed by fused deposition modeling an inner (phi11 *
      42 mm) cylindrical void. The square pores (1.8 * 1.8 mm2 each) fill 50% of outer
      volume, resulting in a 2:1 PET tracer concentration ratio in the void volume with
      respect to porous volume. A matching cylindrical phantom insert is dedicated to
      validate gated radiotherapy. It contains eight peripheral holes and one central
      hole, matching the location of the porous part and the void part of the 3D
      printed insert, respectively. These holes accommodate adaptors for Farmer-type
      ion chamber and cells vials. End-to-end tests were designed for imaging,
      planning, and dose measurements. RESULTS: End-to-end test were performed from 4D
      PET/CT scanning to transferring data to the planning system, target volume
      delineation, and dose measurements. 4D PET/CT scans were acquired of the phantom
      at different respiratory motion patterns and gating windows. A measured 2:1 18F
      FDG concentration ratio between inner void and outer porous volume matched the 3D
      printed design. Measured dose in the dosimetric insert agreed well with planned
      dose on the imaging insert, within 3% for the static phantom and within 5% for
      most breathing patterns. CONCLUSIONS: The novel 3D printed phantom insert mimics
      variable PET tracer uptake typical of tumors. Obtained 4D PET/CT scans are
      suitable for segmentation and treatment planning and delivery in SIB gated
      treatments. Our experiments demonstrate the feasibility of this set of phantom
      inserts serving as end-to-end quality-assurance phantoms of SIB radiotherapy.

PMID- 28766728
TI  - Analytical nuclear excited-state gradients for the Tamm-Dancoff approximation
      using uncoupled frozen-density embedding.
AB  - We report the derivation and implementation of analytical nuclear gradients for
      excited states using time-dependent density functional theory using the Tamm
      Dancoff approximation combined with uncoupled frozen-density embedding using
      density fitting. Explicit equations are presented and discussed. The
      implementation is able to treat singlet as well as triplet states and functionals
      using the local density approximation, the generalized gradient approximation,
      combinations with Hartree-Fock exchange (hybrids), and range-separated
      functionals such as CAM-B3LYP. The new method is benchmarked against
      supermolecule calculations in two case studies: The solvatochromic shift of the
      (vertical) fluorescence energy of 4-aminophthalimide on solvation, and the first
      local excitation of the benzonitrile dimer. Whereas for the 4-aminophthalimide
      water complex deviations of about 0.2 eV are obtained to supermolecular
      calculations, for the benzonitrile dimer the maximum error for adiabatic
      excitation energies is below 0.01 eV due to a weak coupling of the subsystems.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 28766727
TI  - Ethnic disparities in progression to advanced liver disease and overall survival
      in patients with chronic hepatitis C: impact of a sustained virological response.
AB  - BACKGROUND: Chronic hepatitis C (CHC) can lead to cirrhosis and hepatocellular
      carcinoma (HCC). A sustained virological response (SVR) is associated with
      improved outcomes, however, its impact on different ethnic groups is unknown.
      AIM: To evaluate ethnic differences in the natural history of CHC and the impact
      of SVR. METHODS: We conducted a cohort study of 8039 consecutive adult CHC
      patients seen at two medical centres in California between January 1997 and June
      2016. Individual chart review confirmed CHC diagnosis. RESULTS: Asian and
      Hispanic but not African American patients had significantly higher cirrhosis and
      HCC incidence than Caucasians. On multivariate analysis, Hispanic ethnicity was
      independently associated with increased cirrhosis (adjusted HR 1.37, CI,
      confidence interval 1.10-1.71, P=.006) and HCC risk (adjusted HR 1.47, CI 1.13
      1.92, P=.004) compared to Caucasian. Asian ethnicity had a significant
      association with cirrhosis (adjusted HR 1.28, CI 1.02-1.61, P=.034) and HCC risk
      (adjusted HR 1.29, CI 0.94-1.77, P=.025). In patients who achieved SVR, Hispanic
      ethnicity was no longer independently associated with cirrhosis (adjusted HR
      1.76, CI 0.66-4.71, P=.26) or HCC (adjusted HR 1.05, CI 0.27-4.08, P=.94); nor
      was Asian ethnicity (adjusted HR 0.62, CI 0.21-1.82, P=.38 for cirrhosis; 2.01,
      CI 0.63-6.36, P=.24 for HCC). Similar findings were observed with overall
      survival among the ethnicities by SVR status. CONCLUSION: Hispanic and Asian
      ethnicity was independently associated with increased cirrhosis and HCC risk.
      Achieving an SVR eliminates the ethnic disparity in liver disease progression and
      overall survival between Hispanic and Asian vs Caucasian CHC patients.

PMID- 28766729
TI  - Estimating and modeling charge transfer from the SAPT induction energy.
AB  - Recent studies using quantum mechanics energy decomposition methods, for example,
      SAPT and ALMO, have revealed that the charge transfer energy may play an
      important role in short ranged inter-molecular interactions, and have a different
      distance dependence comparing with the polarization energy. However, the charge
      transfer energy component has been ignored in most current polarizable or non
      polarizable force fields. In this work, first, we proposed an empirical
      decomposition of SAPT induction energy into charge transfer and polarization
      energy that mimics the regularized SAPT method (ED-SAPT). This empirical
      decomposition is free of the divergence issue, hence providing a good reference
      for force field development. Then, we further extended this concept in the
      context of AMOEBA polarizable force field, proposed a consistent approach to
      treat the charge transfer phenomenon. Current results show a promising
      application of this charge transfer model in future force field development. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28766730
TI  - Hope, Coping, and Relationship Quality in Mothers of Children With Down Syndrome.
AB  - Parenting a child with Down syndrome may pose unique challenges for parents'
      relationship quality. This study used structural equation modeling with a sample
      of 351 mothers of children with Down syndrome to test if hope mediated the
      association between mothers' various coping behaviors and mothers' relationship
      quality. Hope was defined as a generalized positive state that comes from a
      personal sense of agency. Results indicated a greater degree of religious coping
      and internal coping were each significantly associated with more hope, whereas
      support seeking was not related with more hope. Higher hope was significantly
      associated with greater relationship quality. Bootstrapped indirect effects from
      both religious coping and internal coping to hope, and then hope to relationship
      quality, were identified. Implications for therapists and future research are
      described.

PMID- 28766731
TI  - Microparticles from stored red blood cells enhance procoagulant and
      proinflammatory activity.
AB  - BACKGROUND: The pathomechanisms of morbidity due to blood transfusions are not
      yet entirely understood. Elevated levels of red blood cell-derived microparticles
      (RMPs) are found in coagulation-related pathologies and also in stored blood.
      Previous research has shown that RMPs mediate transfusion-related complications
      by the intrinsic pathway. We hypothesized that RMPs might play a role in post
      transfusion thrombotic complications by enhancing procoagulant activity also
      through the extrinsic pathway of coagulation. STUDY DESIGN AND METHODS: In this
      laboratory study, blood from 18 healthy volunteers was stimulated with
      microparticles from expired stored red blood cells. Various clotting parameters
      were recorded. Flow cytometry, enzyme-linked immunosorbent assays, and real-time
      polymerase chain reaction were used to investigate possible mediating mechanisms.
      RESULTS: The addition of RMPs shortened the clotting time from 194 to 161 seconds
      (p < 0.001). After incubation with RMPs, there was increased expression of tissue
      factor (TF) on monocytes and in plasma. TF messenger RNA expression increased in
      a time-dependent and concentration-dependent manner. There was a significant
      induction of interleukin-1beta and interleukin-6. After stimulation with RMPs,
      there was a significant increase in the number of activated platelets, an
      increased percentage of PAC-1/CD62P (procaspase activating compound-1/platelet
      surface P-selectin) double-positive platelets, and an increased number of
      platelet-neutrophil duplets and platelet-monocyte duplets, indicating enhanced
      interaction of platelets with neutrophils and monocytes. Levels of CXCL-8 (C-X-C
      motif chemokine ligand 1) and interleukin-6 were significantly higher after
      treatment with RMPs. CONCLUSION: Our results suggest that RMPs trigger
      coagulation through TF signaling, induce the secretion of proinflammatory
      cytokines, and induce cell-cell interaction between platelets and neutrophils.
      Thus, under certain conditions, RMPs could play a role in post-transfusion
      complications through these mechanisms.

PMID- 28766732
TI  - Electronic structure, magnetic properties, and mixed valence character of Ce2 Ni3
      Si5 from first principles calculations.
AB  - Cerium intermetallic compounds exhibit anomalous physical properties such as
      heavy fermion and Kondo behaviors. Here, an ab initio study of the electronic
      structure, magnetic properties, and mixed valence character of Ce2 Ni3 Si5 using
      density functional theory (DFT) is presented. Two theoretical methods, including
      pure Perdew-Burke-Ernzerhof (PBE) and PBE + U, are used. In this study, Ce3+ and
      Ce4+ are considered as two different constituents in the unit cell. The formation
      energy calculations on the DFT level propose that Ce is in a stable mixed valence
      of 3.379 at 0 K. The calculated electronic structure shows that Ce2 Ni3 Si5 is a
      metallic compound with a contribution at the Fermi level from Ce 4f and Ni 3d
      states. With the inclusion of the effective Hubbard parameter (Ueff ), the five
      valence electrons of 5 Ce3+ ions are distributed only on Ce3+ 4f orbitals.
      Therefore, the occupied Ce3+ 4f band is located in the valence band (VB) while
      Ce4+ 4f orbitals are empty and Located at the Fermi level. The calculated
      magnetic moment in Ce2 Ni3 Si5 is only due to cerium (Ce3+ ) in good agreement
      with the experimental results. The Ueff value of 5.4 eV provides a reasonable
      magnetic moment of 0.981 MUB for the unpaired electron per Ce3+ ion. These
      results may serve as a guide for studying present mixed valence cerium-based
      compounds. (c) 2017 Wiley Periodicals, Inc.

PMID- 28766733
TI  - A riot on campus: The effects of social identity complexity on emotions and
      reparative attitudes after ingroup-perpetrated violence.
AB  - When a group commits a transgression, members who identify closely with the group
      often engage in defensive strategies in which they are less likely to experience
      guilt and shame in response to the transgression than are less identified group
      members. Subsequently, highly identified group members are often less willing to
      offer reparations to the injured parties. Because appropriate emotional responses
      and reparations are critical to community reconciliation, the present
      investigation examined whether social identity complexity-the degree to which
      individuals perceive their multiple social identities as interrelated-reduced
      these defensive responses. In the aftermath of a campus riot, emotional responses
      and reparative attitudes of undergraduate students were assessed. Results
      indicated that individuals who closely identified with the university were in
      fact capable of experiencing guilt and shame, but only if they also had complex
      social identities. A path model indicated that emotional responses, in turn,
      predicted willingness to provide reparations to the campus community.
      Accordingly, social identity complexity provides a new approach to understanding
      responses to ingroup-perpetrated violence.

PMID- 28766734
TI  - Pressure flow pattern of varicocele veins and its correlation with testicular
      blood flow and semen parameters.
AB  - The pressure pattern in varicocele veins of infertile patients and its
      correlation with semen quality and testicular blood flow was determined.
      Consecutive patients at andro-urology clinic of a teaching hospital undergoing
      microsurgical varicocelectomy were included. Their semen quality and testicular
      blood flow were determined. Peak systolic velocity (PSV) and resistive index (RI)
      of subcapsular and intraparenchymal branches of testicular artery were noted by
      colour Doppler ultrasonography. During surgery before ligation of varicocele
      veins, intravenous pressures of internal spermatic (ISV) and external spermatic
      (ESV) veins were determined at baseline and after Valsalva manoeuvre. Thirty
      patients, 20-45 years old, were evaluated. Baseline pressure for maximum dilated
      ISV (A), less dilated ISV (B) and ESV was 15.93 +/- 6.34, 12.38 +/- 4.60 and
      12.92 +/- 5.65 mm. Hg, respectively, which increased after Valsalva by 104.4%,
      116.2% and 38.22% respectively. Correlation (r = -.71; p < .05) was appreciated
      between percentage increase in pressure of ISV B with PSV of intraparenchymal
      testicular arteries and progressive motility (r = -.759; p < .05), nonprogressive
      motility (r = -.738; p < .05) and morphology (r = -.653; p = .07) of spermatozoa.
      In conclusion, ISV develops higher pressure on Valsalva as compared to ESV and
      has correlation with semen quality and testicular blood flow.

PMID- 28766735
TI  - Relationship between tooth loss and peripheral arterial disease among women.
AB  - AIM: We assessed the longitudinal association between tooth loss and peripheral
      arterial disease (PAD) within the Nurses' Health Study. MATERIALS AND METHODS:
      After excluding participants with prior cardiovascular diseases, 277 of 79,663
      women were confirmed as PAD cases during 16 years of follow-up. Number of teeth
      and recent tooth loss were reported initially in 1992. Subsequent tooth loss was
      recorded in 1996 and in 2000. We evaluated the associations of baseline number of
      teeth and recent tooth loss with risk of PAD, adjusting for age, smoking,
      diabetes, hypertension, high cholesterol, aspirin use, family history of
      myocardial infarction, BMI, alcohol consumption, physical activity,
      postmenopausal hormone use, and use of vitamin E, vitamin D, multivitamin and
      calcium. RESULTS: Incident tooth loss during follow-up was significantly
      associated with higher hazard of PAD (HR = 1.31 95% CI: 1.00-1.71). However, the
      association appeared inverse among never smokers. There was no dose-response
      relationship between baseline number of teeth and PAD. CONCLUSIONS: Tooth loss
      showed a modest association with PAD, but no dose-response relationship was
      observed.

PMID- 28766736
TI  - Cutaneous intravascular natural killer/T cell lymphoma with peculiar
      immunophenotype.
AB  - Intravascular lymphoma (IVL) is a rare entity. Most cases are a variant of
      extranodal diffuse large B cell lymphoma, and fewer than 10% of the published
      cases are of T cell origin. Only intravascular B cell lymphoma is recognized as a
      distinct entity in the most recent World Health Organization (WHO) classification
      of lymphoproliferative disorders. We describe a case of cutaneous natural killer
      (NK)/T IVL, with a cytotoxic immunophenotype and Epstein-Barr virus (EBV)
      positivity. However, our case was immunohistochemically negative not only for T
      cell receptor (TCR)-betaF1 and TCR-gamma (TCR-silent), but also for CD56, making
      it the first triple-negative NK/T IVL case to be described. We urge recognition
      of this NK/T cell lineage intravascular lymphoma due to its particular
      immunophenotypical profile and its unvarying relationship with EBV. Its
      occurrence should not be considered a coincidence, but rather a key aspect of the
      pathogenic background of this haematological neoplasm.

PMID- 28766737
TI  - CD117 expression in adenosquamous carcinoma.

PMID- 28766738
TI  - Major shifts in Amazon wildlife populations from recent intensification of floods
      and drought.
AB  - In the western Amazon Basin, recent intensification of river-level cycles has
      increased flooding during the wet seasons and decreased precipitation during the
      dry season. Greater than normal floods occurred in 2009 and in all years from
      2011 to 2015 during high-water seasons, and a drought occurred during the 2010
      low-water season. During these years, we surveyed populations of terrestrial,
      arboreal, and aquatic wildlife in a seasonally flooded Amazonian forest in the
      Loreto region of Peru (99,780 km2 ) to study the effects of intensification of
      natural climatic fluctuations on wildlife populations and in turn effects on
      resource use by local people. Shifts in fish and terrestrial mammal populations
      occurred during consecutive years of high floods and the drought of 2010. As
      floods intensified, terrestrial mammal populations decreased by 95%. Fish,
      waterfowl, and otter (Pteronura brasiliensis) abundances increased during years
      of intensive floods, whereas river dolphin and caiman populations had stable
      abundances. Arboreal species, including, macaws, game birds, primates, felids,
      and other arboreal mammals had stable populations and were not affected directly
      by high floods. The drought of 2010 had the opposite effect: fish, waterfowl, and
      dolphin populations decreased, and populations of terrestrial and arboreal
      species remained stable. Ungulates and large rodents are important sources of
      food and income for local people, and large declines in these animals has shifted
      resource use of people living in the flooded forests away from hunting to a
      greater reliance on fish.

PMID- 28766739
TI  - Serum Levels of a Cathepsin-K Generated Periostin Fragment Predict Incident Low
      Trauma Fractures in Postmenopausal Women Independently of BMD and FRAX.
AB  - Periostin is a matricellular protein involved in bone formation and bone matrix
      organization, but it is also produced by other tissues. Its circulating levels
      have been weakly associated with bone microstructure and prevalent fractures,
      possibly because periostin measured by the current commercial assays does not
      specifically reflect bone metabolism. In this context, we developed a new ELISA
      for a periostin fragment resulting from cathepsin K digestion (K-Postn). We
      hypothesized that circulating K-Postn levels could be associated with bone
      fragility. A total of 695 women (age 65.0 +/- 1.5 years), enrolled in the Geneva
      Retirees Cohort (GERICO), were prospectively evaluated over 4.7 +/- 1.9 years for
      the occurrence of low-trauma fractures. At baseline, we measured serum periostin,
      K-Postn, and bone turnover markers (BTMs), distal radius and tibia microstructure
      by HR-pQCT, hip and lumbar spine aBMD by DXA, and estimated fracture probability
      using the Fracture Risk Assessment Tool (FRAX). Sixty-six women sustained a low
      trauma clinical fracture during the follow-up. Total periostin was not associated
      with fractures (HR [95% CI] per SD: 1.19 [0.89 to 1.59], p = 0.24). In contrast,
      K-Postn was significantly higher in the fracture versus nonfracture group (57.5
      +/- 36.6 ng/mL versus 42.5 +/- 23.4 ng/mL, p < 0.001) and associated with
      fracture risk (HR [95%CI] per SD: 2.14 [1.54 to 2.97], p < 0.001). After
      adjustment for aBMD, FRAX, bone microstructure, or BTMs, K-Postn remained
      significantly associated with fracture risk. The performance of the fracture
      prediction models was improved by adding K-Postn to aBMD or FRAX (Harrell C index
      for fracture: 0.70 for aBMD + K-Post versus 0.58 for aBMD alone, p = 0.001; 0.73
      for FRAX + K-Postn versus 0.65 for FRAX alone, p = 0.005). Circulating K-Postn
      predicts incident fractures independently of BMD, BTMs, and FRAX in
      postmenopausal women. Hence measurement of a periostin fragment resulting from in
      vivo cathepsin K digestion may help to identify subjects at high risk of
      fracture. (c) 2017 American Society for Bone and Mineral Research.

PMID- 28766740
TI  - Formatting an experiential learning education module to encourage dysphagia
      assessment in apheresis patients.
AB  - BACKGROUND: Dysphagia screening is oftentimes a focus of hospitalized patients,
      but dysphagia can also occur in outpatient settings. Dysphagia can be overlooked
      by nurses and clinicians, and it is therefore important to educate nurses on the
      importance of dysphagia screenings. METHODS: This was a randomized prospective
      pilot study to compare the effect of experiential learning versus traditional
      PowerPoint learning regarding nurses' attitudes towards performing dysphagia
      screening in an outpatient setting. Twelve pre and post-test surveys were
      collected from nurses working in outpatient apheresis about their attitudes
      towards dysphagia screening. Additionally, 128 electronic medical records (EMR)
      were reviewed to determine if education increased the occurrence of dysphagia
      screening. RESULTS: There was a statistically significant difference in the pre
      vs. post-test group scores (P < .001), but due to small sample size, there was
      insufficient evidence to reject the null hypothesis that nurses had changed their
      attitudes towards dysphagia screening. Comparing documentation of dysphagia
      assessment in the EMR, there was not a significant difference in practice before
      or after the educational intervention (P = 0.18). CONCLUSIONS: The study results
      showed that the both types of teaching strategies are possible with nurses and
      they were receptive to both. Although the results of this study did not show a
      significant difference in practice, more research is needed to determine how to
      raise awareness and put this into practice.

PMID- 28766741
TI  - The role of social license in conservation.

PMID- 28766742
TI  - Research gaps in routine health information system design barriers to data
      quality and use in low- and middle-income countries: A literature review.
AB  - Despite the potential impact of health information system (HIS) design barriers
      on health data quality and use and, ultimately, health outcomes in low- and
      middle-income countries (LMICs), no comprehensive literature review has been
      conducted to study them in this context. We therefore conducted a formal
      literature review to understand system design barriers to data quality and use in
      LMICs and to identify any major research gaps related understanding how system
      design affects data use. We conducted an electronic search across 4 scientific
      databases-PubMed, Web of Science, Embase, and Global Health-and consulted a data
      use expert. Following a systematic inclusion and exclusion process, 316
      publications (316 abstracts and 18 full papers) were included in the review. We
      found a paucity of scientific publications that explicitly describe system design
      factors that hamper data quality or data use for decision making. Although user
      involvement, work flow, human-computer interactions, and user experience are
      critical aspects of system design, our findings suggest that these issues are not
      discussed or conceptualized in the literature. Findings also showed that
      individual training efforts focus primarily on imparting data analysis skills.
      The adverse impact of HIS design barriers on data integrity and health system
      performance may be even bigger in LMICs than elsewhere, leading to errors in
      population health management and clinical care. We argue for integrating systems
      thinking into HIS strengthening efforts to reduce the HIS design-user reality
      gap.

PMID- 28766744
TI  - Active offer of health services in French in Ontario: Analysis of reorganization
      and management strategies of health care organizations.
AB  - BACKGROUND: The availability of health services in French is not only weak but
      also inexistent in some regions in Canada. As a result, estimated 78% of more
      than a million of Francophones living in a minority situation in Canada
      experience difficulties accessing health care in French. To promote the delivery
      of health services in French, publicly funded organizations are encouraged to
      take measures to ensure that French-language services are clearly visible,
      available, easily accessible, and equivalent to the quality of services offered
      in English. OBJECTIVE: This study examines the reorganization and management
      strategies taken by health care organizations in Ontario that provide health
      services in French. METHODS: Review and analysis of designation plans of a sample
      of health care organizations. RESULTS: Few health care organizations providing
      services in French have concrete strategies to guarantee availability,
      visibility, and accessibility of French-language services. CONCLUSIONS:
      Implementation of the active offer of French-language services is likely to be
      difficult and slow. The Ontario government must strengthen collaboration with
      health care organizations, Francophone communities, and other key actors
      participating in the designation process to help health care organizations build
      capacities for the effective offer of French-language services.

PMID- 28766745
TI  - Exploring the microbiome of healthy and diseased peri-implant sites using
      Illumina sequencing.
AB  - AIM: To compare the microbiome of healthy (H) and diseased (P) peri-implant sites
      and determine the core peri-implant microbiome. MATERIALS AND METHODS: Submucosal
      biofilms from 32 H and 35 P sites were analysed using 16S rRNA sequencing (MiSeq,
      Illumina), QIIME and HOMINGS. Differences between groups were determined using
      principal coordinate analysis (PCoA), t tests and Wilcoxon rank sum test and FDR
      adjusted. The peri-implant core microbiome was determined. RESULTS: PCoA showed
      partitioning between H and P at all taxonomic levels. Bacteroidetes, Spirochetes
      and Synergistetes were higher in P, while Actinobacteria prevailed in H (p <
      .05). Porphyromonas and Treponema were more abundant in P while Rothia and
      Neisseria were higher in H (p < .05). The core peri-implant microbiome contained
      Fusobacterium, Parvimonas and Campylobacter sp. T. denticola, and P. gingivalis
      levels were higher in P, as well as F. alocis, F. fastidiosum and T. maltophilum
      (p < .05). CONCLUSION: The peri-implantitis microbiome is commensal-depleted and
      pathogen-enriched, harbouring traditional and new pathogens. The core peri
      implant microbiome harbours taxa from genera often associated with periodontal
      inflammation.

PMID- 28766743
TI  - Mouse retinal ganglion cell signalling is dynamically modulated through parallel
      anterograde activation of cannabinoid and vanilloid pathways.
AB  - KEY POINTS: Retinal cells use vanilloid transient receptor potential (TRP)
      channels to integrate light-evoked signals with ambient mechanical, chemical and
      temperature information. Localization and function of the polymodal non-selective
      cation channel TRPV1 (transient receptor potential vanilloid isoform 1) remains
      elusive. TRPV1 is expressed in a subset of mouse retinal ganglion cells (RGCs)
      with peak expression in the mid-peripheral retina. Endocannabinoids directly
      activate TRPV1 and inhibit it through cannabinoid type 1 receptors (CB1Rs) and
      cAMP pathways. Activity-dependent endocannabinoid release may modulate signal
      gain in RGCs through simultaneous manipulation of calcium and cAMP signals
      mediated by TRPV1 and CB1R. ABSTRACT: How retinal ganglion cells (RGCs) process
      and integrate synaptic, mechanical, swelling stimuli with light inputs is an area
      of intense debate. The nociceptive cation channel TRPV1 (transient receptor
      potential vanilloid type 1) modulates RGC Ca2+ signals and excitability yet the
      proportion of RGCs that express it remains unclear. Furthermore, TRPV1's response
      to endocannabinoids (eCBs), the putative endogenous retinal activators, is
      unknown, as is the potential modulation by cannabinoid receptors (CBRs). The
      density of TRPV1-expressing RGCs in the Ai9:Trpv1 reporter mouse peaked in the
      mid-peripheral retina. TRPV1 agonists including capsaicin (CAP) and the eCBs
      anandamide and N-arachidonoyl-dopamine elevated [Ca2+ ]i in 30-40% of wild-type
      RGCs, with effects suppressed by TRPV1 antagonists capsazepine (CPZ) and BCTC ((4
      (3-chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide),
      and lacking in Trpv1-/- cells. The cannabinoid receptor type 1 (CB1R) colocalized
      with TRPV1:tdTomato expression. Its agonists 2-arachidonoylglycerol (2-AG) and
      WIN55,122 inhibited CAP-induced [Ca2+ ]i signals in adult, but not early
      postnatal, RGCs. The suppressive effect of 2-AG on TRPV1 activation was emulated
      by positive modulators of the protein kinase A (PKA) pathway, inhibited by the
      CB1R antagonist rimonabant and Gi uncoupler pertussis toxin, and absent in Cnr1-/
      RGCs. We conclude that TRPV1 is a modulator of Ca2+ homeostasis in a subset of
      RGCs that show non-uniform distribution across the mouse retina. Non-retrograde
      eCB-mediated modulation of RGC signalling involves a dynamic push-pull between
      direct TRPV1 activation and PKA-dependent regulation of channel inactivation,
      with potential functions in setting the bandwidth of postsynaptic responses,
      sensitivity to mechanical/excitotoxic stress and neuroprotection.

PMID- 28766746
TI  - Sensory effects of transient receptor potential channel agonists on whole mouth
      saliva extensional rheology.
AB  - : The extensional rheology (ER) of saliva is a property associated with its
      ability to coat surfaces and is important for the maintenance of a normal mouth
      feeling. Transient receptor potential (TRP) channels are expressed in the oral
      cavity and this study investigated how the sensory effects of TRP channel
      agonists modify the ER of saliva. Healthy volunteers rinsed with solutions
      containing a TRP agonist. Unstimulated whole mouth saliva (WMS) was collected
      prior to rinsing and WMS was collected during the first and second minutes after
      the mouth rinse. The Spinnbarkeit of the collected saliva was measured using a
      Neva Meter. The nonivamide (TRPV1) mouth rinse increased WMS ER from 37.0 (+/-
      6.3) mm to 49.3 (+/- 5.1) mm when compared with the vehicle control, which itself
      had no effect on WMS ER. However, this effect was short-lived and ER of WMS was
      not increased in the second minute after the nonivamide mouth rinse. The menthol
      (TRPM8) mouth rinse resulted in an increase up to 57.8 (+/- 7.8) mm in WMS ER
      from the vehicle control and returned to control levels in the second minute. The
      cinnamaldehyde (TRPA1) mouth rinse resulted in no change in WMS ER. It can be
      concluded that nonivamide and menthol mouth rinsing has a short-term effect of
      increasing WMS ER, an effect not observed after cinnamaldehyde rinsing. We
      hypothesize that the activation of some TRP channels in the oral cavity results
      in changes in the salivary protein composition that in turn alters WMS ER.
      PRACTICAL APPLICATIONS: Identifying compounds that modify the physical properties
      of saliva in a desirable way is important in developing treatments for conditions
      associated with changes in the physical properties of saliva such as xerostomia
      (also known as dry mouth). Furthermore, understanding the rheology of saliva
      contributes to the elucidation of food oral processing which is of importance to
      food manufacturers.

PMID- 28766747
TI  - Impact of salivary enzyme activity on the oral perception of starch containing
      foods.
AB  - : It has long been held that product developers should not rely solely on
      instrumental measures of texture. This study examined the widely accepted effects
      of salivary alpha amylase on mouth thinning during oral processing. To understand
      this phenomenon, 13 descriptive panelists were trained to manipulate starch
      thickened semisolid foods and note when changes in the perceived thickness
      occurred. The panelists were subsequently grouped based on their reports of how
      quickly these foods broke down in their oral cavity. The accepted effect of
      salivary alpha amylase was then analyzed and found to be consistent across the
      starch thickened foods examined but different among the panelists. Thus it became
      clear that starch containing foods with long residence times in the mouth can be
      perceived differently among people based on their amylase activity, making
      descriptive profiling difficult to calibrate. This study suggests that classic
      sensory techniques could also have limitations when considering the oral
      processing of starchy foods, especially those with long residence times in the
      oral cavity. Panelists' individual salivary amylase activity was not measured in
      this study. PRACTICAL APPLICATIONS: Food texture is an important sensory
      attribute that affects consumers' acceptance of products. Semisolid foods such as
      puddings and yogurts are expected to thin as the food is manipulated in the
      mouth. By the same token, starch systems in chewy candies can also be impacted
      over long periods of mastication. Understanding the impact of salivary amylase on
      how quickly these foods breakdown is important to developing foods that will be
      acceptable to consumers. Developers with an understanding of the effects salivary
      amylase has on various starches can lead them to design products that perform
      more consistently across individuals with different activity levels of salivary
      alpha amylase.

PMID- 28766748
TI  - The 4th international conference on Food Oral Processing, July 2016.

PMID- 28766749
TI  - Sensory and analytical characterization of the "cool-melting" perception of
      commercial spreads.
AB  - : Butters, margarines and table spreads are water-in-oil emulsions. Melting
      characteristics of these products are important for flavor release and consumer
      acceptance. One characteristic that is believed to discriminate butters from
      margarines is a cooling sensation perceived in-mouth while consuming these
      products. Here, we investigated different methods to characterize sensorically
      and analytically the "cool-melting" properties of commercial butter and
      margarines. Our results show that butter indeed can be distinguished from
      margarines based on their "cool-melting" properties. Furthermore, changes in
      enthalpy as measured through DSC and solid fat content are good predictors of the
      "cool-melting" effect of spreads. PRACTICAL APPLICATIONS: By understanding the
      mechanisms of the "cool-melting" perception of spreads, and linking them to
      analytical measurements, we can create an in-vitro quantification method of "cool
      melting." This method can eventually help directing product development to
      achieve the desire product profile and increase consumer acceptance and liking of
      margarines and low-fat spread products. In this study we did not assess the
      impact of "cool-melting" on consumer perception, which would be the next step in
      understanding the drivers of liking of spread products.

PMID- 28766750
TI  - Using food comfortability to compare food's sensory characteristics expectations
      of elderly people with or without oral health problems.
AB  - : Food consumption is by far the most important point where food's organoleptic
      properties can be perceived and can elicit sensory pleasure. Ageing is often
      accompanied by oral impairments. Those impairments may impact food perception by
      changing texture perception and the release of flavor components, which have a
      significant impact on food acceptability. The present study aimed at evaluating
      the impact of oral health on the perception of food comfortability in an elderly
      population. This was achieved by asking elderly people with a good oral health
      and elderly people with poor oral health to rate six cereal products and six meat
      products using a food comfortability questionnaire. Thirty-seven and 35 elderly
      people (65-87 years old) underwent either a cereal or meat session, respectively.
      The present study showed very few effects of dental and saliva status on food
      perception. For the cereal products, a significant effect of dental status was
      observed for one texture descriptor and one flavor descriptor, and a significant
      effect of salivary status was observed for two texture descriptors and one flavor
      descriptor. For the meat products, a significant effect of dental status and a
      significant effect of salivary status were observed on one flavor descriptor. For
      both products, no significant impact of dental or salivary status was observed on
      the general perception of food oral comfort nor on food bolus formation. Future
      studies exploring the impact of a broader set of oral parameters and potential
      adapting factors are needed to further explore the results of the present study.
      PRACTICAL APPLICATIONS: During oral food consumption, mastication, salivation,
      and swallowing play a key role in the acceptance of food and beverages by
      modulating the perception of texture, taste, and aroma, as well as providing
      eating comfort by assisting the food breakdown process into a bolus that can be
      safely swallowed. The age-related oral impairments such as loss of teeth,
      decrease in salivary flow or dysphagia are known to have an impact on food
      consumption. However, very few products are developed to skirt those impairments.
      Therefore, in the context of an ageing population, there is a need to develop
      functional foods that meet the specific nutritional needs of the elderly
      population, as well as a well-balanced flavor and texture framework. Considering
      the large interindividual variability observed on the elderly people, developing
      adapted functional foods is a major challenge for the food industry and society.

PMID- 28766751
TI  - The slip extrusion test: A novel method to characterise bolus properties.
AB  - : The role of mastication is to prepare a bolus for safe swallowing. The Swallow
      Safe model defines deformability, slippiness, and cohesiveness as key properties
      that influence whether a bolus is safe to swallow. Defining these properties
      numerically is difficult and current instruments used for bolus analysis have
      limitations. The slip extrusion test (SET) was developed to objectively measure
      the swallowability of the bolus through determination of its resistance to
      deformation and slip. The test measures the force needed to extrude a bolus
      through a bag as it is pulled through a pair of rollers, imitating the swallowing
      action of a bolus. Three food model systems were used to evaluate the SET: (a)
      viscous solutions with varying viscosity, (b) gels with varying hardness, and (c)
      particulate systems of varying cohesion. The test was applied to peanut boluses
      produced in vivo to demonstrate its potential in characterizing boluses. The
      deformation and slip resistance measurements correlated well with the hardness
      and viscosity measurements of the gels and viscous solutions respectively
      (correlation coefficient r = .94 between deformation resistance and hardness; r =
      .85 for slip resistance and hardness in gels; r = .98 for deformation resistance
      and viscosity; r = .93 for slip resistance and viscosity in solutions). The
      advantage of the SET is it can evaluate the swallowability of a wide range of
      foods of different structure and composition. It could potentially be used to
      investigate the properties of boluses throughout oral processing and help in
      establishing the criteria for a safe to swallow bolus in a quantitative way.
      PRACTICAL APPLICATIONS: The test could be used to measure bolus properties from
      the initial stages of breakdown to the point of swallow for all types of food.
      The ability to measure the changes in bolus properties through all stages of
      breakdown using the same instrument is a significant development. The resistance
      to deformation and slip are quantitative measurements that could potentially be
      used to further develop the Swallow Safe model by providing numerical limits to
      the identified properties. This could be of interest to the development of foods
      for dysphagia sufferers.

PMID- 28766752
TI  - Unlocking opportunities in food design for infants, children, and the elderly:
      Understanding milestones in chewing and swallowing across the lifespan for new
      innovations.
AB  - : Intake of a variety of foods increases the likelihood of good general health.
      From as early as life in utero, humans are exposed to flavor. Further flavor
      imprinting occurs via breast milk, increasing the likelihood of acceptance of a
      variety flavors when solids are introduced. While first foods need to be smooth
      and runny, experience managing soft lumps is required for rudimentary development
      of chewing skills. Texture experiences are critical to providing building blocks
      for food acceptance and gradual increase in the range of food textures eaten.
      Persistence in offering flavors and textures on multiple occasions increases the
      likelihood of acceptance of new foods. Opportunities exist in novel food texture
      use and flavor bridging to improve food variety in children. During adulthood
      lifestyle changes impact on chewing and gastrointestinal efficiency affecting the
      variety of food consumed. Foods that are moist, and encourage the consumer to
      slow down and savor food may reduce diseases affecting the esophagus. The aging
      process sees an increase in medication use with an impact on reduction in saliva
      flow. Further, physiologic changes in taste and olfaction that occur with aging
      may see elders benefit from novel food design that utilizes the intact trigeminal
      system. New food design opportunities exist in the areas of carbonation,
      dissolvable solids, microencapsulation of flavor volatiles or pressurized carbon
      dioxide granules. The use of standardized nomenclature for food labeling,
      description, and measurement methods such as that used by the International
      Dysphagia Diet Standardisation Initiative is advocated to accelerate food oral
      processing research. PRACTICAL APPLICATION: The human feeding, chewing, and
      swallowing mechanism adapts and changes over the life span. There are
      opportunities to influence flavor development from as early as life in utero, and
      through milk feeds. Infants also need exposure to soft lumps to develop
      rudimentary chewing skills that lay the foundation for mature chewing. Melt-in
      the-mouth textures and familiar flavors can help children to bridge to new food
      and diminish development of picky eating. Similar textures can also be used for
      the elderly particularly if used with food flavors and compounds that excite the
      trigeminal system to promote increased food variety. Adults taking medication
      with dry mouth side effects benefit from moist foods. Special populations, such
      as those with swallowing difficulties, may benefit from use of micro encapsulated
      compounds that trigger the trigeminal pathway. Introduction of a food texture
      labeling system is advocated.

PMID- 28766753
TI  - To Keep this Disease from Killing You: Cultural Competence, Consonance, and
      Health among HIV-positive Women in Kenya.
AB  - The HIV/AIDS crisis continues in sub-Saharan Africa, where nearly 70% of
      infections are found. Despite recent efforts to supply antiretroviral therapy to
      those infected, most are not receiving medication and are forced to rely on self
      management to remain healthy. In Kenya, many of those infected are women living
      in extreme poverty. This article presents the findings of research among poor
      women in Nairobi that examined the relationship between knowledge of a cultural
      model of self-managing HIV/AIDS, cultural consonance, and health. This
      biocultural study expands on earlier findings showing that knowledge of the model
      (competence) is a significant predictor of health by examining here how behavior
      consistent with that knowledge (consonance) affects health outcomes, as measured
      by CD4 counts, perceived stress, depressive symptoms, and recent illnesses.

PMID- 28766754
TI  - Grounding by Attention Simulation in Peripersonal Space: Pupils Dilate to Pinch
      Grip But Not Big Size Nominal Classifier.
AB  - Grammatical categories represent implicit knowledge, and it is not known if such
      abstract linguistic knowledge can be continuously grounded in real-life
      experiences, nor is it known what types of mental states can be simulated. A
      former study showed that attention bias in peripersonal space (PPS) affects
      reaction times in grammatical congruency judgments of nominal classifiers,
      suggesting that simulated semantics may include reenactment of attention. In this
      study, we contrasted a Chinese nominal classifier used with nouns denoting pinch
      grip objects with a classifier for nouns with big object referents in a pupil
      dilation experiment. Twenty Chinese native speakers read grammatical and
      ungrammatical classifier-noun combinations and made grammaticality judgment while
      their pupillary responses were measured. It was found that their pupils dilated
      significantly more to the pinch grip classifier than to the big object
      classifier, indicating attention simulation in PPS. Pupil dilations were also
      significantly larger with congruent trials on the whole than in incongruent
      trials, but crucially, congruency and classifier semantics were independent of
      each other. No such effects were found in controls.

PMID- 28766755
TI  - Does baseline depression increase the risk of unexplained and accidental falls in
      a cohort of community-dwelling older people? Data from The Irish Longitudinal
      Study on Ageing (TILDA).
AB  - BACKGROUND: Depression independently increases the risk of falls in older people,
      but the mechanism for this relationship, as well as the specific falls type
      involved, remains unclear. Accidental falls (AFs) are due to slips or trips,
      while the cause of unexplained falls (UFs) is not immediately apparent and can
      include unrecognised syncope. METHOD: This longitudinal study examines the
      relationship between baseline depression and subsequent falls, both accidental
      and unexplained, at 2-year follow-up in a cohort of community dwelling adults
      aged >=50 years. Baseline depression was defined as a score >=16 on The Centre
      for Epidemiological Studies Depression Scale. At follow-up, participants were
      assessed regarding falls since last interview. RESULTS: One-third (228/647) of
      the depressed group had fallen at follow-up, compared with 22% (1388/6243) of the
      nondepressed group (P < .001). Multiple logistic regression models demonstrated
      that depression was associated with an odds ratio of 1.58 (1.31-1.89) P < .001;
      1.24 (1.00-1.52), P = .046; and 1.89 (1.45-2.46), P < .001 for total falls, AFs
      and UFs, respectively, after controlling for relevant covariates. Participants
      with depression who fell were more likely to have prior falls, functional
      impairment and slower gait when compared with depressed participants who did not
      fall. DISCUSSION: The risk of falls associated with depression in older adults is
      more marked for UFs, with the association for AFs approaching borderline
      significance only. This finding is important because UFs require focused clinical
      assessment with attention to potential causes such as cardiac arrhythmia or
      orthostatic hypotension.

PMID- 28766756
TI  - Efficacy of low-level laser therapy compared to steroid therapy in the treatment
      of oral lichen planus: A systematic review.
AB  - BACKGROUND: Low-level laser therapy (LLLT) has been proposed as a potential
      treatment strategy for the treatment of oral lichen planus (OLP). The aim of this
      systematic review was to assess the efficacy of LLLT, in comparison with
      corticosteroid therapy, in the treatment of OLP. MATERIALS AND METHODS: This
      systematic review aimed to address the following focused question: "Does LLLT
      yield better clinical outcomes than corticosteroid therapy in the treatment of
      OLP?" Indexed databases were searched up to and including April 2017. Clinical
      trials in humans diagnosed clinically and/or histologically with OLP allocated to
      test (LLLT) versus control (steroid therapy) groups were included. RESULTS: Five
      clinical studies were included. The risk of bias was considered high in four
      studies and moderate in one study. Laser wavelengths, power, spot size, and
      duration of laser exposure ranged between 630 and 970 nm, 10-3000 mW, 0.2-1.0 cm2
      , and 6-480 seconds, respectively. The follow-up period ranged from 4 to 48
      weeks. All included studies reporting clinical scores showed that LLLT was
      effective in the treatment of OLP in adult patients at follow-up. Three studies
      showed significantly higher improvements with topical use of corticosteroids
      compared to LLLT, while one study showed significant improvement with LLLT. One
      study showed comparable outcomes between LLLT and corticosteroid application.
      CONCLUSION: It remains debatable whether LLLT is more effective as compared to
      corticosteroids in the treatment of OLP, given that the scientific evidence is
      weak. These findings are preliminary and further randomized clinical trials are
      recommended.

PMID- 28766757
TI  - Sesamol ameliorates radiation induced DNA damage in hematopoietic system of whole
      body gamma-irradiated mice.
AB  - Ionizing radiation exposure is harmful and at high doses can lead to acute
      hematopoietic radiation syndrome. Therefore, agents that can protect
      hematopoietic system are important for development of radioprotector. Sesamol is
      a potential molecule for development of radioprotector due to its strong free
      radical scavenging and antioxidant properties. In the present study, sesamol was
      evaluated for its role in DNA damage and repair in hematopoietic system of gamma
      irradiated CB57BL/6 mice and compared with amifostine. C57BL/6 male mice were
      administered with sesamol 20 mg/kg (i.p.) followed by 2 Gy whole body irradiation
      (WBI) at 30 min. Mice were sacrificed at 0.5, 3, 24 h postirradiation; bone
      marrow, splenocytes, and peripheral blood lymphocytes were isolated to measure
      DNA damages and repair using alkaline comet,gamma-H2AXand micronucleus assays. An
      increase in % of tail DNA was observed in all organs of WBI mice. Whereas in pre
      administered sesamol reduced %DNA in tail (P <= 0.05). Sesamol has also reduced
      formation of radiation induced gamma-H2AX foci after 0.5 h in these organs and
      further lowered to respective control values at 24 h of WBI. Similar reduction of
      % DNA in tail and gamma-H2AX foci were observed with amifostine (P <= 0.05).
      Analysis of mnPCE frequency at 24 h has revealed similar extent of protection by
      sesamol and amifostine. Interestingly, both sesamol and amifostine, alone and
      with radiation, also increased the granulocytes count significantly compared to
      the control (P <= 0.05). These findings suggest that sesamol has strong potential
      to protect hematopoietic system by lowering radiation induced DNA damages and can
      prevent acute hematopoietic syndrome in mice. Environ. Mol. Mutagen. 59:79-90,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 28766758
TI  - Comparisons of neutrophil-, monocyte-, eosinophil-, and basophil- lymphocyte
      ratios among various systemic autoimmune rheumatic diseases.
AB  - This study was aimed to evaluate levels of neutrophil- (NLR), monocyte- (MLR),
      eosinophil- (ELR), and basophil-lymphocyte ratio (BLR) and their association with
      inflammatory markers in systemic autoimmune rheumatic diseases (SARDs). A total
      of 1139 SARD patients and 170 healthy individuals were enrolled. Clinical and
      laboratory data were extracted. NLR and MLR were significantly increased, but BLR
      decreased in most SARD patients (p < 0.05). ELR were significantly decreased in
      systemic lupus erythematosus (SLE) patients, but increased in those with other
      SARDs (p < 0.001). In SLE patients, C-reactive protein (CRP) showed positive
      correlation with NLR, MLR, and BLR. IgG negatively correlated with NLR, and did
      positively with ELR. IgM negatively correlated with NLR and MLR. In those with
      rheumatoid arthritis (RA), ankylosing spondylitis (AS), and osteoarthritis (OA),
      NLR and MLR positively correlated with erythrocyte sedimentation rate (ESR) and
      CRP. In primary Sjogren's syndrome (pSS) patients, ESR showed positive
      correlation with NLR and MLR. IgA had positive correlation with BLR. In
      polymyositis/dermatomyositis (PM/DM) patients, ESR and CRP positively correlated
      with NLR. Additionally, significant correlations were also found between CRP and
      BLR, IgG and ELR, IgM and ELR. In systemic sclerosis (SSc) patients, clear
      correlations were only observed between CRP and NLR or MLR. In mixed connective
      tissue disease (MCTD) patients, NLR positively correlated with ESR and CRP, while
      NLR and MLR did negatively with IgM. In polymyalgia rheumatic (PMR) patients, MLR
      positively correlated with CRP, while ELR did negatively with IgG. This study
      demonstrated increased NLR and MLR and deceased BLR in most SARDs, decreased ELR
      in SLE and increased ELR in other SARDs. Furthermore, NLR and MLR may be useful
      tools to reflect inflammatory status of SARDs.

PMID- 28766759
TI  - Value of a flow cytometry cross-match in the setting of a negative complement
      dependent cytotoxicity cross-match in heart transplant recipients.
AB  - Complement-dependent cytotoxicity cross-match (CDCXM) is used for evaluation of
      preformed HLA-specific antibodies in patients undergoing heart transplantation.
      Flow cytometry cross-match (FCXM) is a more sensitive assay and used with
      increasing frequency. To determine the clinical relevance of a positive FCXM in
      the context of negative CDCXM in heart transplantation, the United Network for
      Organ Sharing (UNOS) database was analyzed. Kaplan-Meier analysis and Cox
      proportional hazard modeling were used to assess graft survival for three
      different patient cohorts defined by cross-match results: T-cell and B-cell
      CDCXM+ ("CDCXM+" cohort), CDCXM- but T-cell and/or B-cell FCXM+ ("FCXM+" cohort),
      and T-cell/B-cell CDCXM- and FCXM- ("XM-" cohort). During the study period, 2558
      patients met inclusion criteria (10.7% CDCXM+, 18.8% FCXM+, 65.5% XM-). CDCXM+
      patients had significantly decreased graft survival compared to FCXM+ and XM-
      cohorts (P = .003 and <.001, respectively). CDCXM- and FCXM+ patients did not
      have decreased graft survival compared to XM- patients (P = .09). In multivariate
      analysis, only CDCXM+ was associated with decreased graft survival (HR 1.22, 95%
      CI 1.01-1.49). In conclusion, positive FCXM in the context of negative CDCXM does
      not confer increased risk of graft failure. Further study is needed to understand
      implications of CDCXM and FCXM testing in heart transplant recipients.

PMID- 28766760
TI  - The methylation status and expression of human telomerase reverse transcriptase
      is significantly high in oral carcinogenesis.
AB  - Telomerase activity is present in most cancers and is tightly regulated by the
      expression of human telomerase reverse transcriptase (hTERT). Hypermethylation in
      the promoter region of hTERT contributes to the regulation of hTERT expression.
      In this study, we investigated the methylation and expression of hTERT in oral
      squamous cell carcinoma (OSCC), oral leukoplakia, and normal oral mucosa.
      Furthermore, we investigated the significance of hTERT to the clinicopathological
      findings of OSCC. 35 OSCC, 50 oral leukoplakia (epithelial dysplasia n = 25,
      squamous cell hyperplasia n = 25), and 10 normal oral mucosa samples were
      investigated through methylation-specific PCR. Immunohistochemistry was analyzed
      in 35 OSCC, 50 oral leukoplakia, and 4 normal oral mucosa samples. The
      methylation and expression of hTERT increased from normal oral mucosa to oral
      leukoplakia to OSCC. In OSCC, all samples were methylated. However, partial
      methylation (20%) or unmethylation (80%), but never complete methylation, was
      observed in normal oral mucosa. Additionally, hTERT expression correlated with
      cervical lymph node metastasis. These results suggested that the methylation and
      expression of hTERT is high in oral carcinogenesis and may play an important role
      in oral cancer. hTERT expression may also be predictive of cervical lymph node
      metastasis.

PMID- 28766761
TI  - A comparison of electrospray ionization, atmospheric pressure chemical
      ionization, and atmospheric pressure photoionization for the liquid
      chromatography/tandem mass spectrometric analysis of bisphenols. Application to
      bisphenols in thermal paper receipts and U.S. currency notes.
AB  - RATIONALE: Human health concerns have arisen for common bisphenols (BPA and BPS)
      as well as new structural analogs. While native sulfone bisphenols and sulfone
      derivatized bisphenols are amenable to electrospray ionization (ESI), alternative
      ionization methods such as atmospheric pressure chemical ionization (APCI) and
      APPI were investigated to analyze non-derivatized, non-sulfone-containing
      bisphenols. METHODS: Ionization of bisphenols using negative ion APPI was
      compared to negative ion ESI and negative ion APCI for their relative abilities
      to produce [M-H]- precursor ions for subsequent collision-induced dissociation
      (CID) in a triple quadrupole mass analyzer. Multiple reaction monitoring (MRM)
      transitions were optimized using the most sensitive ion transitions and coupled
      with high-performance liquid chromatographic (HPLC) separation to detect and
      quantify BPA, BPB, BPF, BPZ, BPAP, BPS, and BPSIP. RESULTS: APPI provides a more
      universal sensitivity over ESI toward the classes of bisphenols studied with
      detection limits of 20-50 pg on-column. The LC/APPI-MS/MS method was used to
      examine the levels of these seven bisphenols in thermal paper receipts and in
      U.S. paper currency. In both receipts and currency, BPA and BPS were the dominant
      bisphenols found in the paper. CONCLUSIONS: The measurement of BPA and bisphenol
      analogs in thermal paper receipts and transfer of bisphenols from receipts to
      currency notes is of increasing importance to assess human dermal exposure routes
      to this class of compounds. Equivalent sensitivity between sulfone- and non
      sulfone-containing bisphenols is achievable through the use of alternate
      ionization sources such as APCI and APPI that circumvents tedious and time
      consuming derivatization procedures to render analytical sensitivity by ESI.

PMID- 28766762
TI  - Is laxative misuse associated with binge eating? Examination of laxative misuse
      among individuals seeking treatment for eating disorders.
AB  - OBJECTIVE: Our research focuses on laxative misuse, which has been understudied
      in previous eating disorders (ED) research, to understand its prevalence and
      correlates among individuals seeking ED treatment. We also test the association
      between laxative misuse and binge eating to examine the assumption that laxative
      misuse is intended to compensate for binge eating. METHOD: Participants were
      2,295 ED treatment-seeking adults (29.5 +/- 10.5) who self-reported their
      disordered eating behaviors on the Eating Disorder Questionnaire. Participants
      met DSM-5 diagnostic criteria for anorexia nervosa (AN: 11.5%, n = 264), bulimia
      nervosa (BN: 39.0%, n = 896), binge-eating disorder (14.9%, n = 343), or other
      specified feeding or eating disorder (34.5%, n = 792). RESULTS: Nearly 25% of
      participants (n = 571) reported misusing laxatives during the last month.
      Laxative misusers with AN reported significantly higher frequency of laxative
      misuse relative to misusers with BN (F(1,440) = 5.226, p = .023, etap2= .012).
      Among laxative misusers, there was no association between frequency of binge
      eating and frequency of laxative misuse. DISCUSSION: Laxative misusers with AN
      tend to misuse laxatives more frequently than those with BN. Binge eating was not
      related to laxative misuse in our sample. Future research may use real-time data
      collection to understand the function of laxative misuse and to validate our
      cross-sectional findings.

PMID- 28766763
TI  - Enhanced molecular typing of Treponema pallidum identified a new tp0548 Gene type
      in Shandong, China.

PMID- 28766764
TI  - Bioactive Triterpenes from the Root of Salvia miltiorrhiza Bunge.
AB  - Danshen (Salvia miltiorrhiza) is a well-known medicinal herb in the oriental
      medicine. The current study on bioactive triterpenoid in the root of S.
      miltiorrhiza led to the isolation of a new highly hydroxylated ursane-type
      triterpene, urs-12-ene-2alpha,3beta,7beta,16alpha-tetraol (1) and five known ones
      including 2beta-hydroxypomolic acid (2), maslinic acid (3), asiatic acid (4),
      ursolic acid (5), and oleanolic acid (6). Their structures were elucidated on the
      basis of extensive spectroscopic analyses and comparison with literature data.
      The antiproliferative testing against HL-60 cells revealed that the new compound
      1 and ursolic acid (5) showed weak and moderate activities with IC50 values of
      42.2 and 11.7 MUM. In addition, compounds 1-3 showed inhibitory effect on ghrelin
      activity. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28766765
TI  - Impact of oral potentially malignant disorders on quality of life.
AB  - BACKGROUND: Oral potentially malignant disorders (OPMDs) could have a significant
      psychological impact on patients, principally because of the unknown risk of
      malignant transformation, while the physical and functional impairments could
      differ. This study aimed to assess the impact of three different OPMDs and their
      disease stages on the quality of life (QoL) of affected patients. METHODS: Oral
      leukoplakia (OL), oral lichen planus (OLP) and oral submucous fibrosis (OSF)
      patients who were undergoing treatment at an oral medicine clinic of a dental
      teaching hospital in India were the study population. All subjects completed the
      recently developed OPMDQoL questionnaire and a short form 12 item (version 2)
      health survey questionnaire (SF-12v2). OPMDQoL questionnaire consists of 20 items
      over four dimensions. A higher score denotes poor OHRQoL. SF-12v2 has two
      components, a Physical Component Summary (PCS) and Mental Component Summary
      (MCS). RESULTS: A total of 150 subjects (50 each of OL, OLP and OSF)
      participated. OL patients (37.7 +/- 7.9) reported significantly better OPMDQoL
      scores than OLP (47.3 +/- 5.8) and OSF (45.4 +/- 9.2) patients. OLP patients
      reported significant problems in obtaining a clear diagnosis for their condition,
      more so than the other OPMDs. OL patients reported fewer problems for the
      dimension, "physical impairment and functional limitations" than the OLP and OSF
      patients. A significant trend was observed with the overall OPMDQoL and MCS,
      deteriorating as the disease stage increased. CONCLUSIONS: OLP and OSF have a
      significant impact on the QoL of affected individuals: OL less so. Increasing
      stage of the disease is associated with worsening QoL.

PMID- 28766766
TI  - Graft quality matters: Impact of KDPI and delayed kidney transplantation in
      combined liver-kidney transplantation.

PMID- 28766767
TI  - Data processing and case identification in an agricultural and logging morbidity
      surveillance study: Trends over time.
AB  - BACKGROUND: Agriculture and logging are dangerous industries, and though data on
      fatal injury exists, less is known about non-fatal injury. Establishing a non
      fatal injury surveillance system is a top priority. Pre-hospital care reports and
      hospitalization data were explored as a low-cost option for ongoing surveillance
      of occupational injury. METHODS: Using pre-hospital care report free-text and
      location codes, along with hospital ICD-9-CM external cause of injury codes, we
      created a surveillance system that tracked farm and logging injuries. RESULTS: In
      Maine and New Hampshire, 1585 injury events were identified (2008-2010). The
      incidence of injuries was 12.4/1000 for agricultural workers, compared to
      10.4/1000 to 12.2/1000 for logging workers. CONCLUSIONS: These estimates are
      consistent with other recent estimates. This system is limited to traumatic
      injury for which medical treatment is administered, and is limited by the
      accuracy of coding and spelling. This system has the potential to be both
      sustainable and low cost.

PMID- 28766768
TI  - Erratum to "Computer-based training (CBT) intervention reduces workplace violence
      and harassment for homecare workers".

PMID- 28766769
TI  - Erratum to "Lung function not affected by asbestos exposure in workers with
      normal Computed Tomography scan".

PMID- 28766770
TI  - The effect of long working hours on cerebrovascular and cardiovascular disease; A
      case-crossover study.
AB  - BACKGROUND: This study investigated the relationship between weekly working hours
      and the occurrence of cerebro-cardiovascular diseases using a case-crossover
      study design. METHODS: We investigated average working hours during the 7 days
      before the onset of illness (hazard period) and average weekly working hours
      between 8 days and 3 months before the onset of cerebro-cardiovascular diseases
      (control period) for 1,042 cases from the workers' compensation database for
      2009. RESULTS: Among all subjects, the odds ratio by conditional logistic
      regression for the risk of cerebro-cardiovascular diseases with a 10 hr increase
      in average weekly working hours was 1.45 (95% confidence interval [CI]: 1.22
      1.72), a significant association. CONCLUSIONS: An increase in average weekly
      working hours may trigger the onset of cerebro-cardiovascular disease. Am. J.
      Ind. Med. 60:753-761, 2017. (c) 2017. Wiley Periodicals, Inc.

PMID- 28766772
TI  - VII. DEVELOPMENTAL TRAJECTORIES OF CHILDREN'S EMOTIONAL REACTIVITY AFTER THE
      BIRTH OF A SIBLING.

PMID- 28766775
TI  - ISSUE INFORMATION - CURRENT MONOGRAPHS LISTING.

PMID- 28766773
TI  - XI. GENERAL DISCUSSION: CHILDREN'S ADJUSTMENT AND ADAPTATION FOLLOWING THE BIRTH
      OF A SIBLING.

PMID- 28766774
TI  - VI. DEVELOPMENTAL TRAJECTORIES OF CHILDREN'S ANXIETY AND DEPRESSION AFTER THE
      BIRTH OF A SIBLING.

PMID- 28766776
TI  - X. DEVELOPMENTAL TRAJECTORIES OF CHILDREN'S SLEEP PROBLEMS AFTER THE BIRTH OF A
      SIBLING.

PMID- 28766777
TI  - III. STABILITY AND CHANGE IN CHILDREN'S EMOTIONAL AND BEHAVIORAL ADJUSTMENT AFTER
      THE BIRTH OF A SIBLING.

PMID- 28766778
TI  - V. DEVELOPMENTAL TRAJECTORIES OF CHILDREN'S ATTENTION PROBLEMS AFTER THE BIRTH OF
      A SIBLING.

PMID- 28766782
TI  - PREDICTING NORMATIVE AND PROBLEMATIC FAMILY PATHWAYS TO THE TRANSITION TO
      SIBLINGHOOD: COMMENTARY ON VOLLING ET AL.'S MONOGRAPH.
AB  - Volling et al.'s monograph provides a rich, thoughtful, and rigorous account of
      how the transition to siblinghood is experienced by the first-born child and the
      family. In their comprehensive longitudinal study, they followed 241 families
      from the prenatal period before the second-born's birth until this child was 12
      months old. Siblings are a critical, but understudied, relationship in children's
      development; the challenges posed in researching sibling dynamics in the context
      of the family are discussed. Prior psychodynamic and developmental research
      literature is critiqued, which places the current study into perspective and
      indicates the important theoretical frameworks (i.e., developmental
      psychopathology and developmental ecological systems) employed by Volling et al.
      to advance our understanding of this critical transition in the life of the
      family. The longitudinal study design, sample characteristics, identification of
      possible trajectories of adjustment (or not) to the birth of the sibling, and
      selection of family and child variables are addressed. The sophisticated
      statistical methods (Growth Mixture Modeling and data mining procedures) employed
      to predict child adjustment in association with parenting variables over time and
      sibling relationship quality at 12 months identified low- and high-risk
      trajectories on the seven subscales of the Child Behavior Check List (CBCL). This
      afforded a nuanced investigation of a variety of potentially problematic child
      behaviors (e.g., aggression, withdrawal, negative emotionality, somatic problems)
      in association with parenting behaviors. A final discussion included study
      limitations, significant strengths, and implications for clinicians and other
      professionals. The study's conclusion is that most children and families are
      resilient, take the birth of a sibling in their stride, and do not exhibit
      empirical evidence of a developmental crisis, as argued by earlier psychodynamic
      authors.

PMID- 28766780
TI  - IX. DEVELOPMENTAL TRAJECTORIES OF CHILDREN'S SOMATIC COMPLAINTS AFTER THE BIRTH
      OF A SIBLING.

PMID- 28766781
TI  - II. METHODS AND PROCEDURES FOR THE FAMILY TRANSITIONS STUDY.

PMID- 28766783
TI  - IV. DEVELOPMENTAL TRAJECTORIES OF CHILDREN'S AGGRESSIVE BEHAVIORS AFTER THE BIRTH
      OF A SIBLING.

PMID- 28766789
TI  - Drinking trajectories of at-risk groups: Does the theory of the collectivity of
      drinking apply?
AB  - INTRODUCTION AND AIMS: Alcohol consumption among Swedish adolescents has halved
      during the last decade. We aim to: (i) investigate whether the overall decrease
      in drinking may conceal an underlying heterogeneity in drinking trajectories
      across at-risk groups that differ with respect to risk for drinking and; (ii)
      assess to what degree alcohol-related harm has responded to this decrease. DESIGN
      AND METHODS: Data were obtained from the nationally representative annual school
      survey of alcohol and drug habits among Swedish ninth-grade students covering the
      period 2000-2012 (n ~ 5000/year). Respondents were divided into five at-risk
      groups ranging from low to high based on their relative ranking on a risk scale
      for drinking. Alcohol consumption was measured by beverage-specific quantity and
      frequency items summarised into a measure of overall drinking in litres of 100%
      alcohol per year. Alcohol-related harm was measured by eight items asking about
      whether the respondent had experienced various alcohol-related negative
      consequences. RESULTS: Drinking and alcohol-related harm decreased in all five at
      risk groups. There was a marked relation between the overall consumption and the
      mean consumption in each of the five at-risk groups. Self-reported alcohol
      related harm decreased during the study period to an extent that was expected
      from the decrease in alcohol consumption. DISCUSSION AND CONCLUSIONS: Alcohol
      consumption among Swedish youth has declined in five groups that were delineated
      based on their relative ranking on a risk factor index. The findings are
      consistent with Skog's theory of the collectivity of drinking behaviour.
      [Norstrom T, Raninen J. Drinking trajectories of at-risk groups: Does the theory
      of the collectivity of drinking apply?.

PMID- 28766790
TI  - Spatial and Lateral Control of Functionality by Rigid Molecular Platforms.
AB  - Surface mounted molecular devices have received significant attention in the
      scientific community because of their unique ability to construct functional
      materials. The key involves the platform on which the molecular device works on
      solid substrates, such as in solid-liquid or solid-vacuum interfaces. Here, we
      outline the concept of rigid molecular platforms to immobilize active
      functionality atop flat surfaces in a controllable manner. Most of these
      (multipodal) platforms have at least three anchoring groups to control the
      spatial arrangement of the protruding functional moieties and form mechanically
      stable and electronically tuned contacts to the underlying substrate. Another
      approach is based on employing of flat aromatic scaffolds bearing perpendicular
      functionalities that form stable lateral assemblies on various surfaces. Emphasis
      is placed on the need for controllable assembly and separation of these tailor
      made molecules that expose functionalities at the molecular scale. The
      discussions are focused on the different molecular designs realizing functional
      3D architectures on surfaces, the role of various anchoring strategies to control
      the spatial arrangement, and structural considerations controlling physical
      features like the coupling to the surface or the available space for sterically
      demanding molecular operations.

PMID- 28766785
TI  - VIII. DEVELOPMENTAL TRAJECTORIES OF CHILDREN'S WITHDRAWAL AFTER THE BIRTH OF A
      SIBLING.

PMID- 28766791
TI  - Symptom burden and patient characteristics: Association with quality of life in
      patients with head and neck cancer undergoing radiotherapy.
AB  - BACKGROUND: Patients with head and neck cancer (HNC) experience diminished
      quality of life (QOL) during and after treatment. This study examined which
      characteristics were associated with QOL over time. METHODS: One hundred thirty
      three patients with HNC from a study of 534 oncology patients rated physical and
      mental QOL using the Short Form-12 5 times from the initiation of radiotherapy
      (RT) through the following 6 months. Linear mixed model analyses examined changes
      over time and associated characteristics. RESULTS: The QOL deteriorated during RT
      and gradually improved after completion. Less social support was negatively
      associated with both physical and mental QOL. Older age, more comorbidities, more
      psychological symptoms, and concomitant chemotherapy (CTX) were negatively
      associated with physical QOL. Male sex, less physical symptoms, surgery before
      RT, and concomitant chemotherapy were positively associated with mental QOL.
      CONCLUSION: Clinicians can use knowledge on time course and associated
      characteristics to identify and inform patients at higher risk for diminished
      QOL.

PMID- 28766787
TI  - I. INTRODUCTION: UNDERSTANDING THE TRANSITION TO SIBLINGHOOD FROM A DEVELOPMENTAL
      PSYCHOPATHOLOGY AND ECOLOGICAL SYSTEMS PERSPECTIVE.

PMID- 28766792
TI  - Will growth in cryptomarket drug buying increase the harms of illicit drugs?
AB  - BACKGROUND AND AIM: Cryptomarkets-on-line, anonymous market-places for illicit
      goods and services that specialize mainly in drugs-account for a small but
      rapidly growing share of the illicit drug market in many countries. Policy
      responses so far are based generally on the assumption that their rise will only
      increase drug harms. In this contribution for debate, we question this
      assumption. METHODS: We provide a narrative review of the emerging literature
      connected to drug cryptomarkets. We use MacCoun & Reuter's formula to understand
      the effect of population-level increases in use on total harm as depending on the
      level of harm associated with each unit of use. We then consider the potential
      for cryptomarkets to increase or decrease the harms and benefits related to each
      unit of drug use, with specific attention to the quality of drugs sold and the
      non-drug-related harms and benefits for customers. RESULTS: It is likely that
      cryptomarkets will increase both the amount and the range of substances that are
      sold. However, we argue that the effects on harms will depend upon whether
      cryptomarkets also increase the quality and safety of products that are sold,
      provide harm-reducing information to consumers and reduce transactional conflict
      involved in drug purchasing. CONCLUSIONS: There is an emerging and rapidly
      growing evidence base connected to the macro and micro harms and benefits of
      cryptomarkets for drug users. Future researchers should use appropriately matched
      comparative designs to establish more firmly the differential harms and benefits
      of sourcing drugs both on- and off-line. While it is unlikely that the on-line
      drug trade can be eradicated completely, cryptomarkets will respond to regulation
      and enforcement in ways that have complex, and sometimes unanticipated, effects
      on both harms and benefits.

PMID- 28766793
TI  - Evaluation of a carers' information programme culturally adapted for South Asian
      families.
AB  - OBJECTIVES: The Alzheimer's Society has culturally adapted an Information
      Programme for South Asian families (IPSAF) who support an individual living with
      dementia. The objectives of this evaluation were to establish whether IPSAF had
      an immediate and medium-term impact on those who attended and how it impacted on
      the wider family and the person with dementia. METHODS: An inclusive, pluralistic
      approach was adopted. Seven focus groups were conducted with 42 participants, and
      37 participated in a pre-post knowledge quiz. Seven family interviews were
      conducted with 17 participants, and 3 families were followed up after 6 months.
      Thematic analysis was conducted on the data. FINDINGS: The IPSAF was found to
      improve participants' knowledge of dementia leading to increased understanding of
      the person with dementia. Participants became more aware of available services
      and accessed services to make use of practical support. IPSAF was reported to
      have an impact for people living with dementia, with carers' newfound
      understanding resulting in some changes in care practice that promoted
      empowerment and independence for people living with dementia. There was also some
      evidence to suggest that IPSAF had an impact on the wider family, with
      participants sharing information about dementia with family members who had not
      attended the programme. Families were continuing to make changes to improve the
      lives of people living with dementia 6 months later, suggesting IPSAF had a
      sustained impact. CONCLUSION: This culturally adapted programme was found to have
      a significant impact on carers, the person with dementia, and the wider family.

PMID- 28766794
TI  - An open-source framework for analyzing N-electron dynamics. II. Hybrid density
      functional theory/configuration interaction methodology.
AB  - In this contribution, we extend our framework for analyzing and visualizing
      correlated many-electron dynamics to non-variational, highly scalable electronic
      structure method. Specifically, an explicitly time-dependent electronic wave
      packet is written as a linear combination of N-electron wave functions at the
      configuration interaction singles (CIS) level, which are obtained from a
      reference time-dependent density functional theory (TDDFT) calculation. The
      procedure is implemented in the open-source Python program detCI@ORBKIT, which
      extends the capabilities of our recently published post-processing toolbox
      (Hermann et al., J. Comput. Chem. 2016, 37, 1511). From the output of standard
      quantum chemistry packages using atom-centered Gaussian-type basis functions, the
      framework exploits the multideterminental structure of the hybrid TDDFT/CIS wave
      packet to compute fundamental one-electron quantities such as difference
      electronic densities, transient electronic flux densities, and transition dipole
      moments. The hybrid scheme is benchmarked against wave function data for the
      laser-driven state selective excitation in LiH. It is shown that all features of
      the electron dynamics are in good quantitative agreement with the higher-level
      method provided a judicious choice of functional is made. Broadband excitation of
      a medium-sized organic chromophore further demonstrates the scalability of the
      method. In addition, the time-dependent flux densities unravel the mechanistic
      details of the simulated charge migration process at a glance. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28766795
TI  - Allergic contact dermatitis caused by epsilon-aminocaproic acid in a purified
      sodium hyaluronate ophthalmic solution.

PMID- 28766796
TI  - Contact allergy caused by methylisothiazolinone in shoe glue.

PMID- 28766797
TI  - Allergic contact dermatitis caused by benzoic acid and lauryl glucoside in a
      sunscreen.

PMID- 28766798
TI  - Assessment of skin sensitization potency of hair dye molecules in vitro.

PMID- 28766799
TI  - Occupational facial contact dermatitis caused by
      methylchloroisothiazolinone/methylisothiazolinone in a stainless steel aerosol
      spray.

PMID- 28766800
TI  - Allergic contact dermatitis caused by clindamycin mimicking 'retinoid flare'.

PMID- 28766801
TI  - The importance of a complete declaration of isothiazolinones in products beyond
      cosmetics.

PMID- 28766802
TI  - Isopropyl myristate contact allergy: could your moisturizer be the culprit?

PMID- 28766803
TI  - Patch testing with the Swedish baseline series supplemented with a textile dye
      mix and gold in Vilnius, Lithuania and Malmo, Sweden.

PMID- 28766804
TI  - Allergic contact dermatitis caused by resorcinol following a temporary black
      henna tattoo.

PMID- 28766805
TI  - Severe allergic contact dermatitis caused by octylisothiazolinone in a leather
      sofa: two new cases.

PMID- 28766806
TI  - Photoallergy to promazine hydrochloride.

PMID- 28766807
TI  - Xplor-NIH for molecular structure determination from NMR and other data sources.
AB  - Xplor-NIH is a popular software package for biomolecular structure determination
      from nuclear magnetic resonance (NMR) and other data sources. Here, some of Xplor
      NIH's most useful data-associated energy terms are reviewed, including newer
      alternative options for using residual dipolar coupling data in structure
      calculations. Further, we discuss new developments in the implementation of
      strict symmetry for the calculation of symmetric homo-oligomers, and in the
      representation of the system as an ensemble of structures to account for motional
      effects. Finally, the different available force fields are presented, among other
      Xplor-NIH capabilities.

PMID- 28766808
TI  - Investigation of the regenerative potential of necrotic mature teeth following
      different revascularisation protocols.
AB  - This study aimed to assess the revascularisation potential of necrotic mature
      teeth in a dog model following different protocols. Periapical infection was
      induced in 54 mature premolars. Teeth were distributed into seven groups: (1)
      Double-antibiotic-paste/Blood clot, (2) Ciprofloxacin/collagen, (3) Double
      antibiotic-paste/Collagen, (4) Modified Tri-antibiotic-paste /collagen, (5)
      Ciprofloxacin/Gelfoam, (6) Double-antibiotic-paste/Gelfoam, and (7) Modified
      Triantibiotic- paste/Gelfoam. Positive and negative controls included infected
      and healthy teeth, respectively, (n = 12 roots/group). Canals were apically
      shaped to size 0.6 mm then disinfected for 1 month. Intra-canal bleeding was
      induced then scaffolds were applied for another month. Teeth and supporting bone
      were surgically sampled. Tissues were histologically scored and vimentin immuno
      intensity was estimated. Ciprofloxacin and Double-antibiotic paste/Collagen
      resulted in significantly better corono-apical tissue ingrowths, vascularity,
      cementum formation and significantly lower inflammatory extents (P < 0.05).These
      groups also showed significantly higher Vimentin intensities, (P < 0.05). The
      applied protocols revascularised necrotic mature canals and reduced inflammation
      particularly in the Ciprofloxacin/collagen and Double-antibiotic-paste/collagen
      groups.

PMID- 28766809
TI  - Generalization of the Schrodinger Theory of Electrons.
AB  - The Schrodinger theory for a system of electrons in the presence of both a static
      and time-dependent electromagnetic field is generalized so as to exhibit the
      intrinsic self-consistent nature of the corresponding Schrodinger equations. This
      is accomplished by proving that the Hamiltonian in the stationary-state and time
      dependent cases {H;H(t)} are exactly known functionals of the corresponding wave
      functions {Psi;Psi(t)}, that is, H=H[Psi] and H(t)=H[Psi(t)]. Thus, the
      Schrodinger equations may be written as H[Psi]Psi=E[Psi]Psi and
      H[Psi(t)]Psi(t)=i?Psi(t)/?t. As a consequence the eiegenfunctions and energy
      eigenvalues {Psi,E} of the stationary-state equation, and the wave function
      Psi(t) of the temporal equation, can be determined self-consistently. The proofs
      are based on the "Quantal Newtonian" first and second laws which are the
      equations of motion for the individual electron amongst the sea of electrons in
      the external fields. The generalization of the Schrodinger equation in this
      manner leads to additional new physics. The traditional description of the
      Schrodinger theory of electrons with the Hamiltonians {H;H(t)} known constitutes
      a special case. (c) 2017 Wiley Periodicals, Inc.

PMID- 28766810
TI  - Evaluation of carotid atherosclerotic plaque surface characteristics utilizing
      simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) technique.
AB  - PURPOSE: To evaluate the feasibility of the Simultaneous Noncontrast Angiography
      and intraPlaque hemorrhage (SNAP) technique in identification of carotid plaque
      surface characteristics compared with the conventional multicontrast vessel wall
      imaging protocol. MATERIALS AND METHODS: Thirty symptomatic patients with carotid
      plaque were recruited and underwent carotid artery magnetic resonance imaging
      (MRI) (3.0T) using a conventional multicontrast protocol and SNAP sequence. As an
      intrinsic multicontrast sequence, SNAP could generate a gray blood reference
      (Ref) image set, a black blood corrected real (CR) image set, and a bright blood
      MR angiography (MRA) image set. A bright blood SNAP Ref2 image was implemented by
      combining Ref and MRA images for facilitating plaque surface characteristics
      evaluation. The presence/absence of calcification (CA), juxtaluminal
      calcification (JCA), and ulceration was assessed. The agreement between SNAP and
      multicontrast vessel wall protocol in identifying CA, JCA, and ulceration was
      analyzed using Cohen's kappa analysis. The interreader and intrareader
      reproducibility of SNAP imaging in identifying plaque surface characteristics was
      also assessed. RESULTS: Good to excellent agreement was found between SNAP and
      conventional multicontrast protocol in identifying CA (kappa = 0.74, 95%
      confidence interval [CI]: 0.54-0.93), JCA (kappa = 0.81, 95% CI: 0.66-0.97), and
      ulceration (kappa = 0.82, 95% CI: 0.65-0.99). In addition, excellent intrareader
      and interreader reproducibility was found for SNAP imaging in identification of
      CA, JCA, and ulceration. CONCLUSION: SNAP imaging showed excellent agreement with
      multicontrast imaging and high reproducibility in identification of both JCA and
      ulceration, suggesting that SNAP imaging may be a time-efficient, alternative
      tool in identification of plaque surface characteristics in carotid arteries.
      LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging
      2018;47:634-639.

PMID- 28766811
TI  - Do sperm parameters and infertility affect sexuality of couples?
AB  - We aimed to analyse the relationship between sperm parameters and International
      Index of Erectile Function (IIEF) score, the Female Sexual Function Index (FSFI)
      score, the testosterone (T) level in infertile men and between FSFI score and
      partners' fertility. Patients were divided into three groups; (group 1:
      azoospermia [n = 57], group 2: sperm count <15 million [n = 41], group 3: sperm
      count >15 million [n = 81]). Patients and their partners filled the IIEF and FSFI
      forms. The normality of the tests was analysed with Kolmogorov-Smirnov and
      Shapiro-Wilk tests. Spearman's rho test, a nonparametric test, was used to
      correlate the data. A value of p < .05 was considered statistically significant.
      There was a positive correlation between the sperm count, other sperm parameters,
      morphology and motility and IIEF score, FSFI score and T (p = .037, .028 and .041
      respectively). We found a positive correlation between IIEF score and FSFI score
      (p = .182). Infertile partners' FSFI score was lower than fertile partners'
      scores (p = .023). Male infertility causes severe sexual dysfunction in couples,
      and female sexual dysfunction increases in parallel to that of men. Male sexual
      function also tends to decrease with low sperm count. While the clinician
      evaluates infertile couples, psychological and sexual functions should also be
      evaluated and patients should not be deprived of appropriate treatment.

PMID- 28766813
TI  - Acute exacerbation of chronic disseminated intravascular coagulation associated
      with thoracoabdominal aortic aneurysm after tooth extraction.
AB  - OBJECTIVE: To present a rare case of persistent bleeding from the tooth
      extraction socket in a patient with chronic disseminated intravascular
      coagulation (DIC). BACKGROUND: Acute exacerbation of chronic DIC occurs by
      various trigger factors. CLINICAL REPORT: The patient's chronic DIC in
      association with thoracoabdominal aortic aneurysm was activated by tooth
      extraction, resulting in persistent bleeding from the socket. CONCLUSION:
      Patients with chronic DIC may have persistent bleeding following tooth
      extraction.

PMID- 28766814
TI  - Conservative endodontic management of a fused tooth: A case report.
AB  - OBJECTIVE: To report a conservative treatment of a rare developmental anomaly.
      CASE REPORT: A 73-year-old patient with previously initiated therapy and acute
      apical abscess of a maxillary right central incisor fused with the supernumerary
      tooth sought treatment. The conservative approach included nonsurgical root canal
      treatment and composite restoration. CONCLUSION: This case illustrates the
      importance of an individual approach when treating anomalous teeth. Priorities in
      pain and infection management to properly and functionally restore teeth should
      be unaffected by age.

PMID- 28766815
TI  - Rhamnolipids and lactonic sophorolipids: natural antimicrobial surfactants for
      oral hygiene.
AB  - AIMS: To assess the efficacy of rhamnolipid (mixture of monorhamnolipid and
      dirhamnolipid congeners), purified monorhamnolipid, dirhamnolipid and lactonic
      sophorolipid biosurfactants against pathogens important for oral hygiene. METHODS
      AND RESULTS: Acquired and produced biosurfactants were fully characterized to
      allow the antimicrobial activity to be assigned to the biosurfactant congeners.
      Antimicrobial activity was assessed using the resazurin-aided microdilution
      method. Mixed rhamnolipid JBR425 (MR) and lactonic sophorolipids (LSLs)
      demonstrated the lowest minimum inhibitory concentration (MIC) which ranged
      between 100 and 400 MUg ml-1 against Streptococcus mutans, Streptococcus oralis,
      Actinomyces naeslundii, Neisseria mucosa and Streptococcus sanguinis. Combining
      these biosurfactants with standard antimicrobial agents namely chlorhexidine,
      sodium lauryl sulphate, tetracycline HCl and ciprofloxacin showed a dramatic drop
      in the MIC values. In addition, in vitro studies demonstrated the biosurfactants'
      ability to prevent and disrupt oral pathogens biofilms. The increased
      permeability of microorganisms treated with biosurfactant, as shown using
      bisbenzimide dye, in part explains the inhibition effect. CONCLUSION: The results
      demonstrate that rhamnolipids and LSLs have the ability to inhibit oral pathogens
      both in planktonic and oral biofilm states. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The findings indicate the potential value of biosurfactants for both oral hygiene
      and the pharmaceutical industries since there is a serious need to reduce the
      reliance on synthetic antimicrobials and antibiotics.

PMID- 28766817
TI  - Redox Active Metal- and Covalent Organic Frameworks for Energy Storage: Balancing
      Porosity and Electrical Conductivity.
AB  - Porous redox-active metal-organic frameworks (MOFs) and covalent organic
      frameworks (COFs) have emerged as electrode materials for energy storage devices.
      These porous frameworks have different levels of intrinsic properties such as low
      solubility, high ionic conductivity (porosity) and low electrical conductivity,
      all of which are critical parameters when utilised as electrode materials. This
      Minireview focuses on recent developments of using porous MOFs/COFs as redox
      active electrode materials for energy storage and strategies to improve their
      electrochemical performance.

PMID- 28766816
TI  - Improving adherence to multiple medications in older people in primary care:
      Selecting intervention components to address patient-reported barriers and
      facilitators.
AB  - BACKGROUND: Medication adherence is vital to ensuring optimal patient outcomes,
      particularly amongst multimorbid older people prescribed multiple medications.
      Interventions targeting adherence often lack a theoretical underpinning and this
      may impact on effectiveness. The theoretical domains framework (TDF) of behaviour
      can aid intervention development by systematically identifying key determinants
      of medication adherence. OBJECTIVES: This study aimed to (i) identify
      determinants (barriers, facilitators) of adherence to multiple medications from
      older people's perspectives; (ii) identify key domains to target for behaviour
      change; and (iii) map key domains to intervention components [behaviour change
      techniques (BCTs)] that could be delivered in an intervention by community
      pharmacists. METHOD: Focus groups were conducted with older people (>65 years)
      receiving >=4 medications. Questions explored the 12 domains of the TDF (eg
      "Knowledge," "Emotion"). Data were analysed using the framework method and
      content analysis. Identification of key domains and mapping to intervention
      components (BCTs) followed established methods. RESULTS: Seven focus groups were
      convened (50 participants). A wide range of determinants were identified as
      barriers (eg forgetfulness, prioritization of medications) and facilitators (eg
      social support, personalized routines) of adherence to multiple medications.
      Eight domains were identified as key targets for behaviour change (eg "Social
      influences," "Memory, attention and decision processes," "Motivation and goals")
      and mapped to 11 intervention components (BCTs) to include in an intervention [eg
      "Social support or encouragement (general)," "Self-monitoring of the behaviour,"
      "Goal-setting (behaviour)"]. CONCLUSION: This study used a theoretical
      underpinning to identify potential intervention components (BCTs). Future work
      will incorporate the selected BCTs into an intervention that will undergo
      feasibility testing in community pharmacies.

PMID- 28766818
TI  - The malaria parasite Plasmodium relictum in the endemic avifauna of eastern Cuba.
AB  - Island populations are vulnerable to introduced pathogens, as evidenced by
      extinction or population decline of several endemic Hawaiian birds caused by the
      malaria parasite, Plasmodium relictum (order Haemosporida). We analyzed blood
      samples from 363 birds caught near Guantanamo Bay, Cuba, for the presence of
      haemosporidian infections. We characterized parasite lineages by determining
      nucleotide variation of the parasite's mitochondrial cyt b gene. Fifty-nine
      individuals were infected, and we identified 7 lineages of haemosporidian
      parasites. Fifty individuals were infected by 6 Haemoproteus sp. lineages,
      including a newly characterized lineage of Haem. (Parahaemoproteus) sp. CUH01.
      Nine individuals carried the P. relictum lineage GRW4, including 5 endemic Cuban
      Grassquits (Tiaris canorus) and 1 migratory Cape May Warbler (Setophaga tigrina).
      A sequence of the merozoite surface protein gene from one Cuban Grassquit
      infected with GRW4 matched that of the Hawaiian haplotype Pr9. Our results
      indicate that resident and migratory Cuban birds are infected with a malaria
      lineage that has severely affected populations of several endemic Hawaiian birds.
      We suggest GRW4 may be associated with the lack of several bird species on Cuba
      that are ubiquitous elsewhere in the West Indies. From the standpoint of avian
      conservation in the Caribbean Basin, it will be important to determine the
      distribution of haemosporidian parasites, especially P. relictum GRW4, in Cuba as
      well as the pathogenicity of this lineage in species that occur and are absent
      from Cuba.

PMID- 28766819
TI  - Structure Determination Techniques Flex Their Muscles.
AB  - A historical challenge: Gas-phase electron diffraction and single-crystal X-ray
      diffraction are both established techniques, but they were both pushed to their
      limits by the challenge posed by the highly flexible tetranitromethane molecule.
      New approaches had to be developed for the structure of the molecule to be
      elucidated.

PMID- 28766820
TI  - Influence of the Respiratory Cycle on Caudal Vena Cava Diameter Measured by
      Sonography in Healthy Foals: A Pilot Study.
AB  - BACKGROUND: Intravascular volume assessment in foals is challenging. In humans,
      intravascular volume status is estimated by the caudal vena cava (CVC)
      collapsibility index (CVC-CI) defined as (CVC diameter at maximum expiration
      [CVCmax ] - CVC diameter at minimal inspiration [CVCmin ])/CVCmax * 100%.
      HYPOTHESIS/OBJECTIVES: To determine whether the CVC could be sonographically
      measured in healthy foals, determine differences in CVCmax and CVCmin , and
      calculate inter- and intrarater variability between 2 examiners. We hypothesized
      that the CVC could be measured sonographically at the subxiphoid view and that
      there would be a difference between CVCmax and CVCmin values. ANIMALS: Sixty
      privately owned foals <1-month-old. METHODS: Prospective study. A longitudinal
      subxiphoid sonographic window in standing foals was used. The CVCmax and CVCmin
      were analyzed by a linear mixed effect model. Inter-rater agreement and
      intrarater variability were expressed by Bland-Altman and intraclass correlation
      coefficients, respectively. RESULTS: Measurements were attained from 58 of 60
      foals with mean age of 15 +/- 7.9 days and mean weight of 75.7 +/- 17.7 kg. The
      CVCmax was significantly different from CVCmin (D = 0.515, SE = 0.031, P <
      0.001). Inter-rater agreement of the CVC-CI differed by an average of -0.9% (95%
      limits of agreement, -12.5 to +10.7%). Intrarater variability of CVCmax was 0.540
      and 0.545, of CVCmin was 0.550 and 0.594, and of CVC-CI was 0.894 and 0.853 for
      observers 1 and 2, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: These
      results indicate it is possible to reliably measure the CVC sonographically in
      healthy foals, and the CVC-CI may prove useful in assessing the intravascular
      volume status in hypovolemic foals.

PMID- 28766821
TI  - Design and Synthesis of Chiral Diene Ligands for RhI -Catalyzed Enantioselective
      Arylation of N-DPP-protected Aldimines: Synthesis of the Antifungal Agent
      Bifonazole.
AB  - Herein we describe the design and synthesis of a novel family of bifunctional,
      chiral bicyclo[2.2.1]heptadiene ligands bearing aryl and secondary amido groups,
      and demonstrate their usefulness in the RhI -catalyzed enantioselective addition
      reaction of arylboronic acids to N-diphenylphosphinyl (N-DPP)-protected
      aldimines. Unlike the analogous RhI -catalysts comprising diene ligands
      substituted with aryl and carboxylic ester groups, or only with aryl groups, the
      addition reaction proceeded with high stereoselectivity. The protocol tolerated a
      range of N-DPP-aldimines and arylboronic acids, producing the desired optically
      active N-DPP-protected amines with yields between 31-99 % and with ee values up
      to 91-99 %. The synthetic utility of the method was demonstrated by the
      conversion of N-DPP-protected amine 3 ae into the antifungal agent, bifonazole
      (13).

PMID- 28766822
TI  - Quantum Chemical Analyses of BH4- and BH3 OH- Hydride Transfers to CO2 in Aqueous
      Solution with Potentials of Mean Force.
AB  - Biomimetic hydride transfer catalysts are a promising route to efficiently
      convert CO2 into more useful products, but a lack of understanding about their
      atomic-scale reaction mechanisms slows their development. To this end, we report
      a computational quantum chemistry study of how aqueous solvation influences CO2
      reduction reactions facilitated by sodium borohydride (NaBH4 ) and a partially
      oxidized derivative (NaBH3 OH). This work compares 0 K reaction barriers from
      nudged elastic band calculations to free-energy barriers obtained at 300 K using
      potentials of mean force from umbrella sampling simulations. We show that
      explicitly treating free energies from reaction pathway sampling has anywhere
      from a small to a large effect on the reaction-energy profiles for aqueous-phase
      hydride transfers to CO2 . Sampling along predefined reaction coordinates is thus
      recommended when it is computationally feasible.

PMID- 28766823
TI  - Isolation of bacteriophages from air using vacuum filtration technique: an
      improved and novel method.
AB  - AIM: Development of a simple and economical air sampler for isolation and
      enrichment of bacteriophages from air samples. METHODS AND RESULTS: A vacuum
      filtration unit with simple modifications was used for isolation of
      bacteriophages from air sampled in the lavatory. Air was sampled at the rate of
      62 l min-1 by bubbling into Mcllvaine buffer for 30 min, which was used as
      bacteriophage solution for enrichment and plaque assessment against individual
      hosts. Alternatively, the aforementioned phage solution was enriched using a host
      consortium before plaque assessment. Phages were isolated in the range of 1-12
      PFU per ml by the first method, whereas enrichment with host consortium gave
      phages around 10- to 1000-folds higher in number. Combining with established
      enrichment method, an improvement of about 10 times in phage isolation efficiency
      was attained. CONCLUSIONS: The method is very useful for studying the natural
      bacteriophages of air, requiring only a basic microbiological laboratory setup
      making it simple and economical. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      brings out a simple, economical air sampler for assessing air bacteriophages that
      can be employed by any microbial laboratory. Although various methods are
      available for studying bacteriophages in water and soil, very limited are
      available for air. To the best of our knowledge, the method developed in this
      study is unique in its design and concept for studying bacteriophages in air. The
      sampler is sterilizable by autoclaving and maintains a healthy rate of airflow
      provided by conventional vacuum pumps. The use of a nonspecific 'trapping
      solution' allows for the qualitative and quantitative study of air
      bacteriophages.

PMID- 28766824
TI  - EKG-based detection of deep brain stimulation in fMRI studies.
AB  - PURPOSE: To assess the impact of synchronization errors between the assumed
      functional MRI paradigm timing and the deep brain stimulation (DBS) on/off
      cycling using a custom electrocardiogram-based triggering system METHODS: A
      detector for measuring and predicting the on/off state of cycling deep brain
      stimulation was developed and tested in six patients in office visits. Three
      electrode electrocardiogram measurements, amplified by a commercial bio
      amplifier, were used as input for a custom electronics box (e-box). The e-box
      transformed the deep brain stimulation waveforms into transistor-transistor logic
      pulses, recorded their timing, and propagated it in time. The e-box was used to
      trigger task-based deep brain stimulation functional MRI scans in 5 additional
      subjects; the impact of timing accuracy on t-test values was investigated in a
      simulation study using the functional MRI data. RESULTS: Following locking to
      each patient's individual waveform, the e-box was shown to predict stimulation
      onset with an average absolute error of 112 +/- 148 ms, 30 min after
      disconnecting from the patients. The subsecond accuracy of the e-box in
      predicting timing onset is more than adequate for our slow varying, 30-/30-s
      on/off stimulation paradigm. Conversely, the experimental deep brain stimulation
      onset prediction accuracy in the absence of the e-box, which could be off by as
      much as 4 to 6 s, could significantly decrease activation strength. CONCLUSIONS:
      Using this detector, stimulation can be accurately synchronized to functional MRI
      acquisitions, without adding any additional hardware in the MRI environment. Magn
      Reson Med 79:2432-2439, 2018. (c) 2017 International Society for Magnetic
      Resonance in Medicine.

PMID- 28766825
TI  - Beyond the BET Family: Targeting CBP/p300 with 4-Acyl Pyrroles.
AB  - Bromodomain and extra-terminal domain (BET) inhibitors are widely used both as
      chemical tools to study the biological role of their targets in living organisms
      and as candidates for drug development against several cancer variants and human
      disorders. However, non-BET bromodomains such as those in p300 and CBP are less
      studied. XDM-CBP is a highly potent and selective inhibitor for the bromodomains
      of CBP and p300 derived from a pan-selective BET BRD-binding fragment. Along with
      X-ray crystal-structure analysis and thermodynamic profiling, XDM-CBP was used in
      screenings of several cancer cell lines in vitro to study its inhibitory
      potential on cancer cell proliferation. XDM-CBP is demonstrated to be a potent
      and selective CBP/p300 inhibitor that acts on specific cancer cell lines, in
      particular malignant melanoma, breast cancer, and leukemia.

PMID- 28766826
TI  - The TGx-28.65 biomarker online application for analysis of transcriptomics data
      to identify DNA damage-inducing chemicals in human cell cultures.
AB  - The TGx-28.65 biomarker is a 65-gene expression profile generated from testing 28
      model chemicals (13 that cause DNA damage and 15 that do not) in human TK6 cells.
      It is used to predict whether a chemical induces DNA damage or not. We expanded
      availability to the biomarker by developing the online TGx-28.65 biomarker
      application for predicting the DNA damage inducing (DDI) potential of suspect
      toxicants tested in p53-proficient human cells and assessing putative mode(s) of
      action (MOA). Applications like this that analyse gene expression data to predict
      the hazard potential of test chemicals hold great promise for risk assessment
      paradigms. The TGx-28.65 biomarker interfaces with an analytical tool to predict
      the probability that a test chemical can directly or indirectly induce DNA
      damage. User submitted in vitro microarray data are compared to the 28-chemical x
      65-gene signature profile and the probability that the data fit the profile for a
      DDI or a non-DDI (NDDI) chemical is calculated. The results are displayed in the
      Results Table, which includes the classification probability and hyperlinks to
      view heatmaps, hierarchical clustering, and principal component analyses of user
      input data in the context of the reference profile. The heatmaps and cluster
      plots, along with the corresponding text data files of fold changes in gene
      expression and Euclidean distances can be downloaded. Review of the test chemical
      data in relationship to the biomarker allows rapid identification of key gene
      alterations associated with DNA damage as well as chemicals in the reference set
      that produced a similar response. Environ. Mol. Mutagen. 58:529-535, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28766827
TI  - Are fluconazole or sertraline dose adjustments necessary with concomitant
      rifampin?

PMID- 28766829
TI  - The NICE 10 minute physical restraint rule: A discussion of the relative risks.

PMID- 28766828
TI  - Technical note: No increase in effective dose from half compared to full rotation
      pelvis cone beam CT.
AB  - PURPOSE: To image the abdomen of a patient with a gantry mounted imaging system
      of a linear accelerator, different cone beam computed tomography (CBCT) protocols
      are available. The whole-body dose of a full rotation abdomen CBCT and a half
      rotation CBCT was compared. In our clinic, both CBCT protocols are used in daily
      routine work. METHODS: With an adult anthropomorphic Alderson phantom, the whole
      body dose per CBCT scan was measured with thermoluminescence dosimeters. The half
      rotation CBCT was applied such that the gantry mounted X-ray source rotated
      around the right side of the phantom. The 183 measurement locations covered all
      ICRP recommended critical organs (except the gonads). The effective dose was
      calculated with the mean organ dose and the corresponding tissue weighting
      factors. A point-by-point dose comparison of both protocols was conducted.
      RESULTS: The effective dose was 5.4 mSv +/-5% and 5.0 mSv +/-5% (estimated type B
      1sigma) for the full and the half rotation CBCT respectively. There was no
      significant difference (alpha = 0.05) in the effective dose within the precision
      of the measurement (1sigma = 5%). The half rotation CBCT displayed an
      inhomogeneous dose distribution in a transversal phantom slice in contrast with
      the full rotation CBCT. In the imaging region, the mean dose was (20.5 +/- 3.4)
      mGy and (19.2 +/- 7.4) mGy (measured type A 1sigma) for the full and the half
      rotation CBCT respectively. CONCLUSION: The half compared to the full rotation
      CBCT displays a smaller field-of-view in a transversal slice and no significant
      difference in the effective dose. Hence, the full rotation CBCT is favorable
      compared to the half rotation CBCT. However, by using the half rotation protocol,
      critical volumes in the patient can be spared compared to the full rotation
      protocol.

PMID- 28766830
TI  - Analysis of panel data under hidden mover-stayer models.
AB  - Analysis of panel data is often challenged by the presence of heterogeneity and
      state misclassification. In this paper, we propose a hidden mover-stayer model to
      facilitate heterogeneity for a population that consists of two subpopulations
      each of movers or of stayers and to simultaneously account for state
      misclassification. We develop an inference procedure based on the expectation
      maximization algorithm by treating the mover-stayer indicator and underlying true
      states as latent variables. We evaluate the performance of the proposed method
      and investigate the impact of ignoring misclassification through simulation
      studies. The proposed method is applied to analyze the data arising from the
      Waterloo Smoking Prevention Project. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28766831
TI  - A commentary on 'A comparison of Bayesian and Monte Carlo sensitivity analysis
      for unmeasured confounding'.

PMID- 28766832
TI  - The relationship between the basal coronary translesional pressure ratio and
      fractional flow reserve.
AB  - AIM: Fractional flow reserve (FFR) allows for physiological definition of
      coronary lesion severity but requires induction of maximal coronary circulation
      hyperemia with administration of adenosine leading to coronary resistive vessel
      vasodilatation. However, the hyperemic response to adenosine, and therefore the
      calculation of FFR, may be affected by dysfunction of the coronary
      microvasculature. The aim was to define the relationship between basal Pd /Pa and
      FFR and identify lesion-independent predictors of the change in Pd /Pa with
      hyperemia. METHODS AND RESULTS: One hundred and sixty-six consecutive patients
      undergoing FFR measurement were prospectively enrolled (mean age 62.6 +/- 10.3
      years, 27% females). Basal Pd /Pa , FFR, and delta Pd /Pa (difference between
      basal Pd /Pa and FFR) were recorded. Independent predictors of delta Pd /Pa
      included angiographic lesion severity, lesion length, gender, body mass index,
      and total cholesterol:HDL cholesterol ratio. The best basal Pd /Pa cutoff value
      to predict lesion physiological significance was 0.87 (positive predictive value
      of 100% for an FFR value <=0.80) and the best cutoff for nonsignificance was 0.93
      (negative predictive value of 98% for an FFR value >0.80). CONCLUSION: The delta
      Pd /Pa may be affected by patient gender, body mass index, and cholesterol
      profile. A basal Pd /Pa value of >=0.93 is highly predictive of an FFR >0.80.
      Conversely, a basal Pd /Pa value of <=0.87 is highly predictive of an FFR <=0.80.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 28766833
TI  - Coronary atherectomy is associated with improved procedural and clinical outcomes
      among patients with calcified coronary lesions: Insights from the VA CART
      program.
AB  - OBJECTIVES: We sought to evaluate the prevalence of calcified coronary lesions
      and the association between the use of atherectomy and clinical outcomes.
      BACKGROUND: Calcified coronary arteries are associated with an increased risk of
      procedural complications during percutaneous coronary intervention (PCI). The
      outcomes of coronary atherectomy for adjunctive treatment of calcified coronary
      lesions are not well described. METHODS: We identified all patients treated for
      calcified coronary lesions at VA hospitals. A propensity weighted cohort was
      created for those treated with or without adjunctive atherectomy to evaluate the
      complications and outcomes between groups. RESULTS: From 2007 to 2015, 9,719
      patients underwent single-vessel PCI for treatment of naive native calcific
      coronary lesions. The proportion of patients undergoing revascularization of
      calcified lesions increased over the study period (P = 0.03) and 1,731 patients
      (18%) were treated with atherectomy. Adjunctive atherectomy was more likely to be
      used in high-risk lesions (76.5% vs. 46.8%, P < 0.001). After propensity
      weighting, coronary atherectomy was associated with a 38% decrease in the odds of
      procedural complications and a 54% decrease in the odds of clinical complications
      (both P = 0.005). There was no difference in rates of 2-year death (HR: 1.07; 95%
      CI: 0.92-1.24), myocardial infarction (HR: 0.96; 95% CI: 0.75-1.23) or target
      vessel revascularization (HR: 0.96; 95% CI: 0.78-1.19) CONCLUSIONS: Percutaneous
      treatment of calcified coronary lesions has increased over time. The adjunctive
      use of coronary atherectomy was associated with a reduction in procedural
      complications among patients with calcified coronary arteries. Two-year TVR, MI
      and overall mortality were similar between the two groups.

PMID- 28766834
TI  - Transseptal puncture using surgical electrocautery in children and adults with
      and without complex congenital heart disease.
AB  - BACKGROUND: Atrial transseptal puncture (TSP) for cardiac catheterization
      procedures remain challenging in children and adults with complex congenital
      heart disease (CHD). OBJECTIVES: We sought to evaluate our experience using
      radiofrequency (RF) current via surgical electrocautery needle for TSP to
      facilitate diagnostic and interventional procedures. METHODS: Retrospective chart
      review of all patients (pts) who underwent TSP using RF energy (10-25 W) via
      surgical electrocautery from three centers from January 2011 to January 2017 were
      evaluated. Echocardiograms were reviewed to define the atrial septum as normal
      and complex (thin aneurysmal, thick/fibrotic, synthetic patch material, and extra
      cardiac conduit). RESULTS: A total of 54 pts underwent 55 successful TSP. Median
      age was 12.5 years (1 day-54 years) and weight was 52.7 kg (2-162). Indications
      for TSP included; EP study and ablation procedures in structurally normal hearts
      (n = 24) and in complex atrial septum/CHD and structural heart disease pts (n =
      30): Electrophysiology study and ablation in 4, diagnostic catheterization in 9,
      and interventional procedures in 17 pts were performed. Atrial TSP was successful
      in 54/55 (98%). Atrial perforation with tiny-small pericardial effusion not
      requiring intervention was noted in 2 pts. TSP was unsuccessful in one critically
      ill neonate with unobstructed TAPVR and restricted atrial septum who experienced
      cardiac arrest requiring CPR, ECMO, and emergent surgery. CONCLUSIONS: RF current
      delivery using surgical electrocautery for TSP is a feasible and an effective
      option in patients with complex CHD for diagnostic, interventional, and
      electrophysiology procedures.

PMID- 28766835
TI  - The expression profile and prognostic value of APE/Ref-1 and NPM1 in high-grade
      serous ovarian adenocarcinoma.
AB  - To analyze the expression trends and clinical significance of
      Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APE1/Ref-1) and Nucleophosmin
      (NPM1) proteins in high-grade serous ovarian adenocarcinoma (HGSC). The
      expressions of APE1/Ref-1 and NPM1 proteins in 94 patients with HGSC were
      determined using the immunohistochemical (IHC) method, and their relationships
      with clinicopathological features were analyzed by the chi2 test or Fisher's
      exact test. The follow-up data, Cox proportional hazards univariate and
      multivariate survival analyses were integrated to evaluate the prognostic factors
      affecting patients with HGSC. In the normal fallopian tubes, APE1/Ref-1 and NPM1
      protein were mainly distributed in the nuclear. The HGSC experienced changes in
      the cellular localization of APE1/Ref-1 and NPM1 protein expressions, which were
      abnormally expressed in the cytoplasm. The rates of abnormal cytoplasmic
      expression of APE1/Ref-1 and NPM1 proteins in 94 patients with HGSC were 69.1%
      and 73.4%, respectively, which were significantly higher than the normal
      fallopian tube tissues (p < 0.05). The abnormal cytoplasmic APE1/Ref-1 and NPM1
      are significantly correlated with the lymph node metastasis, chemosensitivity,
      FIGO staging, and prognosis. The COX multivariate survival analysis showed that
      the abnormal expression of APE1/Ref-1 protein, FIGO staging, and lymph node
      metastasis are independent prognostic factors. Collectively, the abnormal
      cytoplasmic APE1/Ref-1 and NPM1 proteins are associated with the oncogenic
      progression and chemoresistance of HGSC, and predict a poor prognosis.

PMID- 28766836
TI  - Doppler echocardiography underestimates the prevalence and magnitude of mid
      cavity obstruction in patients with symptomatic hypertrophic cardiomyopathy.
AB  - OBJECTIVES: To evaluate utility of Doppler echocardiography in the assessment of
      left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy
      (HCM). BACKGROUND: LVMCO is a relatively under-diagnosed complication of HCM and
      may occur alone or in combination with LV outflow tract obstruction (LVOTO).
      Identifying and quantifying LVMCO and differentiating it from LVOTO has important
      implications for patient management. We aimed to assess diagnostic performance of
      Doppler echocardiography in the assessment of suspected LV obstruction. METHODS:
      Forty symptomatic HCM patients with suspected obstruction underwent cardiac
      catheterization, and comparison of location and magnitude of Doppler derived
      gradients with synchronous invasive measurements (reference standard), at rest
      and isoprenaline stress (IS). RESULTS: Doppler's diagnostic accuracy for any
      obstruction (>=30 mmHg) in this cohort was 75% with false positive and false
      negative rates of 2.5 and 22.5%, respectively. During subanalysis, Doppler's
      diagnostic accuracy for isolated LVOTO in this selected cohort is 83% with false
      positive and false negative rates of 4 and 12.5%, respectively. For LVMCO, the
      accuracy is only 50%, with false positive and false negative rates of 10 and 40%,
      respectively. Doppler gradients for isolated LVOTO were similar to invasive: 85
      +/- 51 and 87 +/- 35 mmHg, respectively (P = 0.77). Doppler gradients in LVMCO
      were consistently lower than invasive: 45 +/- 38 and 81 +/- 31 mmHg, respectively
      (P = 0.0002). Mid-systolic flow cessation and/or contamination of spectral
      signals were identified as causes of Doppler-derived inaccuracies. CONCLUSIONS:
      Doppler echocardiography under-diagnoses and underestimates severity of LVMCO in
      symptomatic HCM patients. Recognition of abrupt mid-systolic flow cessation and
      invasive measurements may improve detection of LVMCO in HCM.

PMID- 28766837
TI  - A case of neuroblastoma in DICER1 syndrome: Chance finding or noncanonical
      causation?
AB  - DICER1 syndrome is an inherited disorder associated with at least a dozen rare,
      mainly pediatric-onset tumors. Its characterization remains incomplete. Some
      studies suggested that neuroblastoma (NB) may be involved in this syndrome. Here,
      we describe the case of a 14-year-old female presenting with a multinodular
      goiter (MNG) and a collision tumor composed of NB and cystic nephroma (CN). She
      is a carrier of a deleterious germline mutation in exon 23 of DICER1 and harbored
      different somatic mutations in the CN and MNG. However, no second hit was found
      in the NB, questioning its status as a DICER1-related tumor.

PMID- 28766838
TI  - Transfusion-transmitted babesiosis leading to severe hemolysis in two patients
      with sickle cell anemia.
AB  - The intracellular parasites Babesia microti and Babesia duncani can be
      transmitted by blood transfusion and cause severe life-threatening hemolytic
      anemia in high-risk patients, including those with sickle cell disease. The
      rarity of the diagnosis, as well as its similar clinical presentation to delayed
      hemolytic transfusion reaction, may lead to a delay in diagnosis, as well as
      inappropriate treatment with steroids or other immunosuppressive agents. The
      morbidity caused by this disease in especially vulnerable populations justifies
      the need for a universal blood-screening program in endemic areas.

PMID- 28766839
TI  - Techniques and outcomes of paravalvular leak repair after transcatheter aortic
      valve replacement.
AB  - OBJECTIVES: To investigate the feasibility, procedural success, and outcomes of
      paravalvular leak (PVL) closure in patients with prior transcatheter aortic valve
      replacement (TAVR). BACKGROUND: PVL after TAVR is associated with adverse patient
      outcomes and increased mortality. Percutaneous PVL closure has emerged as a
      therapeutic strategy for addressing this issue, but data for transcatheter PVL
      repair after TAVR remains limited. METHODS: This is a single center retrospective
      review of PVL closure after TAVR. Patients with balloon-expandable or self
      expanding prostheses were included. Baseline patient demographics, procedural
      characteristics, complications, and clinical outcomes were reviewed. RESULTS: A
      total of 18 patients with clinically significant PVL after TAVR referred for PVL
      closure were identified during the study period. Procedural success resulting in
      successful transcatheter occluder plug delivery was 78% (14 cases). Balloon
      postdilatation (2/4) and valve-in-valve (2/4) were used effectively in the
      remaining patients after an unsuccessful PVL closure attempt. PVL grading by
      echocardiography decreased from moderate or severe to < moderate in 13 patients
      (72%). Adverse events including cardiac tamponade and acute kidney injury
      occurred in 1 case each. One-month all-cause mortality was 11%. CONCLUSION: In
      selected patients, percutaneous PVL repair following TAVR is feasible and
      effective for both balloon-expandable and self-expanding prostheses. Most
      patients undergoing PVL closure after TAVR require a single occluder plug
      placement for reduction in PVL to mild or less.

PMID- 28766841
TI  - Value of flow cytometric analysis of peripheral blood samples in children
      diagnosed with acute lymphoblastic leukemia.
AB  - Diagnostic procedures in children with acute lymphoblastic leukemia (ALL) are
      typically performed under general anesthesia. Anticipation of the diagnosis based
      on findings in peripheral blood allows scheduling of the first dose of
      intrathecal chemotherapy and diagnostic bone marrow (BM) aspirate during a single
      anesthetic. We retrospectively compared paired results of peripheral blood (PB)
      flow cytometric analysis and BM evaluation in 383 children with ALL diagnosed
      consecutively at a single center and found very high concordance of results
      between both tests. We conclude that PB flow cytometry may help streamline
      planning of procedure-related anesthetics during diagnosis and early treatment of
      childhood ALL.

PMID- 28766840
TI  - High birth prevalence of sickle cell disease in Northwestern Tanzania.
AB  - BACKGROUND: Worldwide, hemoglobinopathies affect millions of children.
      Identification of hemoglobin disorders in most sub-Saharan African countries is
      delayed until clinical signs of the disease are present. Limited studies have
      been conducted to understand their prevalence and clinical presentation among
      newborns in resource-limited settings. METHODOLOGY: This was a prospective cohort
      study. Newborns (aged 0-7 days) at two hospitals in Northwestern Tanzania were
      enrolled and followed prospectively for 6 months. Clinical and laboratory
      information were collected at baseline. Participants were screened for
      hemoglobinopathies using high-performance liquid chromatography. Clinical and
      laboratory follow-up was performed at 3 and 6 months for those with
      hemoglobinopathies as well as a comparison group of participants without
      hemoglobinopathies. RESULTS: A total of 919 newborns were enrolled. Among these,
      1.4% (13/919) had sickle cell anemia or Hb S/beta0 -thalassemia (Hb FS), and
      19.7% (181/919) had sickle cell trait or Hb S/beta+ thalassemia (Hb FAS).
      Furthermore, 0.2% (two of 919) had beta+ -thalassemia. Red cell indices compared
      between Hb FS, Hb FAS, and Hb FA were similar at baseline, but hemoglobin was
      lower and red cell distribution width was higher in children with Hb FS at 3- and
      6-month follow-up. Febrile episodes were more common for children with Hb FS at 3
      and 6-month follow-up. CONCLUSION: The prevalence of sickle cell disease among
      neonates born in Northwestern Tanzania is one of the highest in the world.
      Newborn screening is needed early in life to identify neonates with
      hemoglobinopathies so that clinical management may commence and morbidity and
      mortality related to hemoglobinopathies be reduced.

PMID- 28766842
TI  - Methanol Extracts of 28 Hieracium Species from the Balkan Peninsula - Comparative
      LC-MS Analysis, Chemosystematic Evaluation of their Flavonoid and Phenolic Acid
      Profiles and Antioxidant Potentials.
AB  - INTRODUCTION: Hieracium s. str. represents one of the largest and most complex
      genera of flowering plants. As molecular genetics seems unlikely to disentangle
      intricate relationships within this reticulate species complex, analysis of
      flavonoids and phenolic acids, known as good chemosystematic markers, promise to
      be more reliable. Data about pharmacological activity of Hieracium species are
      scarce. OBJECTIVE: Evaluation of the chemosystematic significance of flavonoids
      and phenolic acids of methanol extracts of aerial flowering parts of 28 Hieracium
      species from the Balkans. Additionally, investigation of antioxidant potentials
      of the extracts. METHODS: Comparative qualitative and quantitative analysis of
      flavonoids and phenolic acids was performed by LC-MS. Multivariate statistical
      data analysis included non-metric multidimensional scaling (nMDS), unweighted
      pair-group arithmetic averages (UPGMA) and principal component analysis (PCA).
      Antioxidant activity was evaluated using three colorimetric tests. RESULTS:
      Dominant phenolics in almost all species were luteolin type flavonoids, followed
      by phenolic acids. Although the investigated Hieracium species share many
      compounds, the current classification of the genus was supported by nMDS and
      UPGMA analyses with a good resolution to the group level. Hieracium naegelianum
      was clearly separated from the other investigated species. Spatial and ecological
      distances of the samples were likely to influence unexpected differentiation of
      some groups within H. sect. Pannosa. The vast majority of dominant compounds
      significantly contributed to differences between taxa. The antioxidant potential
      of the extracts was satisfactory and in accordance with their phenolics
      composition. CONCLUSIONS: Comparative LC-MS analysis demonstrated that flavonoids
      and phenolic acids are good indicators of chemosystematic relationships within
      Hieracium, particularly between non-hybrid species and groups from the same
      location. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28766843
TI  - Variations in pediatric emergency medicine physician practices for intravenous
      fluid management in children with sickle cell disease and vaso-occlusive pain: A
      single institution experience.

PMID- 28766844
TI  - Timing of cochlear implantation in auditory neuropathy patients with OTOF
      mutations: Our experience with 10 patients.

PMID- 28766845
TI  - Neural stem cell therapy aiming at better functional recovery after spinal cord
      injury.
AB  - Injury to the spinal cord causes transection of axon fibers and neural cell
      death, resulting in disruption of the neural network and severe functional loss.
      Reconstruction of the damaged neural circuits was once considered to be hopeless
      as the adult mammalian central nervous system has very poor ability to
      regenerate. For this reason, there is currently no effective therapeutic
      treatment for spinal cord injury (SCI). However, with recent developments in stem
      cell research and cell culture technology, regenerative therapy using neural stem
      cell (NSC) transplantation has rapidly been developed, and this therapeutic
      strategy makes it possible to rebuild the destroyed neural circuits. In this
      review, we discuss the recent breakthroughs in NSC transplantation therapy for
      SCI. Developmental Dynamics 247:75-84, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 28766846
TI  - Managing conflicts between economic activities and threatened migratory marine
      species toward creating a multiobjective blue economy.
AB  - Harnessing the economic potential of the oceans is key to combating poverty,
      enhancing food security, and strengthening economies. But the concomitant risk of
      intensified resource extraction to migratory species is worrying given these
      species contribute to important ecological processes, often underpin alternative
      livelihoods, and are mostly already threatened. We thus sought to quantify the
      potential conflict between key economic activities (5 fisheries and hydrocarbon
      exploitation) and sea turtle migration corridors in a region with rapid economic
      development: southern and eastern Africa. We satellite tracked the movement of 20
      loggerhead (Caretta caretta) and 14 leatherback (Dermochelys coriacea) turtles
      during their postnesting migrations. We used movement-based kernel density
      estimation to identify migration corridors for each species. We overlaid these
      corridors on maps of the distribution and intensity of economic activities,
      quantified the extent of overlap and threat posed by each activity on each
      species, and compared the effects of activities. These results were compared with
      annual bycatch rates in the respective fisheries. Both species' 3 corridors
      overlapped most with longline fishing, but the effect was worse for leatherbacks:
      their bycatch rates of approximately 1500/year were substantial relative to the
      regional population size of <100 nesting females/annum. This bycatch rate is
      likely slowing population growth. Artisanal fisheries may be of greater concern
      for loggerheads than for leatherbacks, but the population appears to be
      withstanding the high bycatch rates because it is increasing exponentially. The
      hydrocarbon industry currently has a moderately low impact on both species, but
      mining in key areas (e.g., Southern Mozambique) may undermine >50 years of
      conservation, potentially affecting >80% of loggerheads, 33% of the (critically
      endangered) leatherbacks, and their nesting beaches. We support establishing blue
      economies (i.e., generating wealth from the ocean), but oceans need to be
      carefully zoned and responsibly managed in both space and time to achieve
      economic (resource extraction), ecological (conservation, maintenance of
      processes), and social (maintenance of alternative livelihood opportunities,
      alleviate poverty) objectives.

PMID- 28766847
TI  - Expression of insulin-like growth factor-1 receptor in circulating tumor cells of
      patients with breast cancer is associated with patient outcomes.
AB  - In patients with breast cancer, markers of aggressiveness such as dysregulation
      of the insulin-like growth factor receptor (IGF1R) system and E-cadherin loss are
      commonly observed. Reduced IGF1R expression is correlated with decreased E
      cadherin levels and increased cell motility. We assessed IGF1R and E-cadherin
      expression in circulating tumor cells (CTCs) in patients with breast cancer.
      Peripheral blood mononuclear cells of early (n = 87)- and metastatic (n = 126)
      stage breast cancer patients (obtained prior to adjuvant and first-line
      chemotherapy) were evaluated using double immunofluorescence (IF) staining for
      cytokeratin (CK) and IGF1R. Triple IF using CK, IGF1R, and E-cadherin antibodies
      was performed in selected CTC(+) patients. IGF1R(+) CTCs were more frequently
      observed in early disease than in metastatic disease (86% vs 68% of CTCs, P =
      0.04) stage, whereas IGF1R(-) CTCs were more common in metastatic than in early
      disease (32% vs 14% of CTCs, P = 0.002). 100% of CTC(+) patients with early
      disease, compared to 79% of those with metastatic disease, harbored IGF1R(+) CTCs
      (P = 0.007). Patients with early disease and exclusively IGF1R(+) CTCs had longer
      disease-free (P = 0.02) and overall survival (P = 0.001) compared to patients
      with both IGF1R(+) and IGF1R(-) CTC populations. 67% of early-stage CTC(+)
      patients evaluated had exclusively IGF1R(+)/E-cadherin(+) CTCs, 33% also had
      IGF1R(-)/E-cadherin(-) CTCs, and none had exclusively IGF1R(-)/E-cadherin(-) CTCs
      compared to 17%, 75%, and 8% of metastatic patients, respectively (P = 0.027).
      Similarly, in paired samples of patients with early disease that progressed to
      metastatic disease, the proportion of IGF1R(+)/E-cadherin(+) CTCs was reduced and
      IGF1R(-)/E-cadherin(-) CTCs were increased in the metastatic stage compared to
      early disease stage. IGF1R(+) CTCs are commonly detected in breast cancer, and
      their frequency decreases in the metastatic disease stage. IGF1R(+)/E-cadherin(+)
      CTCs also decrease in metastatic patients. IGF1R(+) CTCs are associated with
      favorable outcomes in early disease stage, suggesting that IGF1R expression is
      correlated with reduced metastatic potential in breast cancer.

PMID- 28766848
TI  - MicroRNA-30a ameliorates hepatic fibrosis by inhibiting Beclin1-mediated
      autophagy.
AB  - We explored the role of microRNA-30a (miR-30a) and the mechanism involved in
      hepatic fibrosis. MiR-30a overexpression was achieved by miR-30a mimics
      transfection in hepatic stellate cells (HSCs) (HSC-T6, LX-2), and miR-30a agomir
      (ago-miR-30a) treatment in mice. MiR-30a levels were measured using TaqMan miRNA
      assay system, and the localization of miR-30a was detected by fluorescence in
      situ hybridization (FISH). The interaction of miR-30a and Beclin1 was confirmed
      by dual-luciferase reporter assay. Autophagic flux was analysed using tandem mRFP
      GFP-LC3 fluorescence microscopy, electron microscopy and Western blot of LC3-II/I
      ratio. MiR-30a was notably down-regulated in activated HSCs and LX-2-exosomes
      induced by TGF-beta1; overexpression of miR-30a down-regulated extracellular
      matrix (ECM), such as alpha-SMA, TIMP-1, and Collagen I expression, and
      suppressed cell viability in HSCs. MiR-30a was significantly down-regulated in
      hepatic fibrosis mice and overexpression of miR-30a prevented BDL-induced
      fibrogenesis, concomitant with the down-regulation of ECM. MiR-30a inhibited HSCs
      autophagy and increased lipid accumulation in HSCs and in mice fibrotic hepatic
      tissues. MiR-30a inhibited its downstream effector of Beclin1 by direct targeting
      its 3'-UTR region. Moreover, Knock-down of Beclin1 by small interfering RNA
      (siRNA) inhibited HSC autophagy and activation in LX-2 cells. In conclusion, miR
      30a is down-regulated in hepatic fibrosis models and its overexpression prevents
      liver fibrogenesis by directly suppressing Beclin1-mediated autophagy; therefore,
      miR-30a may be a new potential therapeutic target for controlling hepatic
      fibrosis.

PMID- 28766850
TI  - Efficacy of a novel swallowing exercise program for chronic dysphagia in long
      term head and neck cancer survivors.
AB  - BACKGROUND: The efficacy of rehabilitative exercises for chronic dysphagia
      treatment in head and neck cancer survivors has not been studied extensively and
      is ambiguous. METHODS: A prospective clinical phase II study using an intensive
      strength training program was carried out in 17 head and neck cancer survivors
      with chronic dysphagia. Both swallow and nonswallow exercises were performed for
      6-8 weeks with a newly developed tool allowing for progressive muscle overload,
      including chin tuck, jaw opening, and effortful swallow exercises. Outcome
      parameters were feasibility, compliance, and parameters for effect. RESULTS:
      Feasibility in terms of the program completion rate was 88%. Compliance with the
      exercises was 97%. After the training period, chin tuck, jaw opening, and
      anterior tongue strength had substantially improved. All but 1 patient reported
      to benefit from the exercises. CONCLUSION: Feasibility and compliance were high.
      Some objective and subjective effects of progressive load on muscle strength and
      swallowing function could be demonstrated.

PMID- 28766851
TI  - Folate deficiency in north Indian children undergoing maintenance chemotherapy
      for acute lymphoblastic leukemia-Implications and outcome.
AB  - BACKGROUND: Treatment-related toxicity and mortality are not uncommon during
      maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL),
      especially in the low- and middle-income countries (LMIC). Undernutrition and
      micronutrient deficiencies are commonly seen in children from LMICs undergoing
      treatment for ALL. The present study examines the prevalence and clinical
      implications of folate deficiency in north Indian children with ALL during the
      maintenance phase of treatment in view of prolonged antifolate treatment and high
      population prevalence of folate deficiency. PROCEDURES: Pre-cycle folate
      levels/deficiency as well as weight for age z-score and serum albumin level were
      determined and correlated with complications of treatment and mortality
      encountered during the maintenance phase of treatment. RESULTS: Twenty-nine of 52
      children enrolled in the study had folate deficiency at some point during
      maintenance chemotherapy. Neutropenia (18 of 29 vs. 4 of 23; P = 0.002),
      thrombocytopenia (17 of 29 vs. 4 of 23; P = 0.005), febrile neutropenia (17 of 29
      vs. 4 of 23; P = 0.005), and need for chemotherapy dose reduction (20 of 29 vs. 7
      of 21; P = 0.01) were more common in folate-deficient children. Maintenance
      deaths were higher (8 of 29 vs. 1 of 23; P = 0.03) and survival lower (P = 0.02)
      in deficient children. In multivariate analysis, hypoalbuminemia (P = 0.02) and
      folate deficiency (P = 0.01) were associated with febrile neutropenia, and folate
      deficiency with maintenance deaths (P = 0.03). CONCLUSIONS: Folate deficiency was
      associated with treatment-related complications and adverse outcome in our
      patients. The risks and benefits of folate supplementation in deficient children
      during maintenance chemotherapy need to be explored with properly designed
      randomized studies in similar settings.

PMID- 28766852
TI  - Serotonin-transporter promoter polymorphism modulates the ability to control food
      intake: Effect on total weight loss.
AB  - SCOPE: The biggest challenge for losing weight is the ability to control the
      amount of food eaten; the tendency to overeat is called disinhibition. Our aims
      were to determine whether (a) the SLC6A4-promoter variant (5-HTTLPR) relates to
      disinhibition; (b) this association could affect total weight-loss during a
      behavioral/dietary treatment for obesity. METHODS AND RESULTS: A total of 2961
      subjects attended voluntarily five weight-loss clinics; a subsample (n = 624) was
      recruited for SLC6A4 genotyping. Total weight-loss, emotional-eating-score and
      disinhibition-score were examined. We observed that: (a) the reduced ability to
      control food intake (disinhibition) is implicated in the impairment to lose
      weight; (b) SLC6A4-promoter variant is implicated in disinhibition. S carriers
      (low-expressing) of the SLC6A4-promoter variant had a lower inhibition capacity
      and showed more failure (1.6 times) to control the amount of food eaten than LL
      (p < 0.05); other factors such as eating while bored, overeating after work at
      night, or craving for specific foods were associated to the SLC6A4 genotype (p <
      0.05); (c) The combination of disinhibition (high disinhibition) and genetics (S
      carrier) had a higher impact on total weight loss than each factor separately.
      CONCLUSIONS: SLC6A4-promoter variant is associated with the ability to control
      food intake and interacts with emotional eating to modulate total weight loss.

PMID- 28766853
TI  - AxTract: Toward microstructure informed tractography.
AB  - Diffusion-weighted (DW) magnetic resonance imaging (MRI) tractography has become
      the tool of choice to probe the human brain's white matter in vivo. However,
      tractography algorithms produce a large number of erroneous streamlines (false
      positives), largely due to complex ambiguous tissue configurations. Moreover, the
      relationship between the resulting streamlines and the underlying white matter
      microstructure characteristics remains poorly understood. In this work, we
      introduce a new approach to simultaneously reconstruct white matter fascicles and
      characterize the apparent distribution of axon diameters within fascicles. To
      achieve this, our method, AxTract, takes full advantage of the recent development
      DW-MRI microstructure acquisition, modeling, and reconstruction techniques. This
      enables AxTract to separate parallel fascicles with different microstructure
      characteristics, hence reducing ambiguities in areas of complex tissue
      configuration. We report a decrease in the incidence of erroneous streamlines
      compared to the conventional deterministic tractography algorithms on simulated
      data. We also report an average increase in streamline density over 15 known
      fascicles of the 34 healthy subjects. Our results suggest that microstructure
      information improves tractography in crossing areas of the white matter.
      Moreover, AxTract provides additional microstructure information along the
      fascicle that can be studied alongside other streamline-based indices. Overall,
      AxTract provides the means to distinguish and follow white matter fascicles using
      their microstructure characteristics, bringing new insights into the white matter
      organization. This is a step forward in microstructure informed tractography,
      paving the way to a new generation of algorithms able to deal with intricate
      configurations of white matter fibers and providing quantitative brain
      connectivity analysis. Hum Brain Mapp 38:5485-5500, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28766854
TI  - Potential misdiagnosis of dysfibrinogenaemia: Data from multicentre studies
      amongst UK NEQAS and PRO-RBDD project laboratories.
AB  - INTRODUCTION: Mutations in fibrinogen (Fgn) genes, causing dysfibrinogenaemia,
      can result in either a bleeding or thrombophilic diathesis. Dysfibrinogenaemia is
      infrequently encountered in hospital laboratories, and the utility of different
      assays in the diagnosis of dysfibrinogenaemia has not previously been explored in
      a multicentre study. We describe here an exercise in which PRO-RBDD project
      (prospective data collection on patients with fibrinogen and Factor XIII
      deficiencies) centres, and UK NEQAS centres, performed investigations for
      dysfibrinogenaemia. METHODS: Samples from donors with dysfibrinogenaemia (sample
      1: gamma p.Arg301Cys, sample 2: Bbeta166Arg3Cys-Fgn Longmont, sample 3: Aalpha
      p.Arg35His) and a normal donor were sent to laboratories for investigation for
      possible dysfibrinogenaemia. Median, coefficient of variation and range were
      determined for each assay method. RESULTS: Results were returned from 62 UK NEQAS
      and 24 PRO-RBDD centres. PT, APTT, Clauss fibrinogen and thrombin times were
      performed by >90% of centres, with 51% performing reptilase times, and 31%
      fibrinogen antigen. All centres identified samples 1 and 3 as abnormal. However,
      39% of centres reported a normal or raised fibrinogen for the Fgn Longmont
      sample, and marked differences in Clauss fibrinogen results with different
      reagents were noted for this sample (median 1.01 g/L vs 5.10 g/L for the two
      mostly widely used reagents). CONCLUSION: In-house studies suggest that the
      method of detection of fibrin clot formation may result in different Clauss
      fibrinogen measurements with FgnLongmont plasma. It is possible that some widely
      used methodologies, both using optical and mechanical end-point detection
      systems, will fail to detect this rare fibrinogen variant.

PMID- 28766855
TI  - Group 6 Transition-Metal/Boron Frustrated Lewis Pair Templates Activate N2 and
      Allow its Facile Borylation and Silylation.
AB  - The reaction of trans-[M(N2 )2 (dppe)2 ] (M=Mo, 1Mo , M=W, 1W ) with B(C6 F5 )3
      (2) provides the adducts [(dppe)2 M=N=N-B(C6 F5 )3 ] (3) which can be regarded as
      M/B transition-metal frustrated Lewis pair (TMFLP) templates activating
      dinitrogen. Easy borylation and silylation of the activated dinitrogen ligands in
      complexes 3 with a hydroborane and hydrosilane occur by splitting of the B-H and
      Si-H bonds between the N2 moiety and the perfluoroaryl borane. This reactivity of
      3 is reminiscent of conventional frustrated Lewis pair chemistry and constitutes
      an unprecedented approach for the functionalization of dinitrogen.

PMID- 28766856
TI  - Alkyl chitosan film-high strength, functional biomaterials.
AB  - Biofilm with strong tensile strength is a topic item in the area of tissue
      engineering, medicine engineering, and so forth. Here we introduced an alkyl
      chitosan film with strong tensile strength and its possibility for an absorbable
      anticoagulation material in vivo was tested in the series of blood test, such as
      dynamic coagulation time, plasma recalcification time and hemolysis. Alkyl
      chitosan film was a better biomaterial than traditional chitosan film in the
      anticoagulation, tissue compatibility and cell compatibility. The unique trait of
      alkyl chitosan film may be for its greater contact angle and hydrophobicity
      ability to reduce the adsorption capacity for the blood component and the
      activity of fibrinolytic enzymes, enhance the antibacterial capacity than
      chitosan film. Moreover, none of chitosan film or butyl chitosan film exhibited
      quick inflammation or other disadvantage and degraded quickly by implanted test.
      Therefore, Alkyl chitosan film is of prospective properties as an implantable,
      absorbable agent for tissue heals, and this material need further research. (c)
      2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3034-3041, 2017.

PMID- 28766857
TI  - Birmingham vasculitis activity score of more than 9.5 at diagnosis is an
      independent predictor of refractory disease in granulomatosis with polyangiitis.
AB  - AIM: We investigated whether clinical manifestations, anti-neutrophil cytoplasmic
      antibodies (ANCAs), Birmingham vasculitis activity score (BVAS) for
      granulomatosis with polyangiitis (GPA) and five factor score (FFS) at diagnosis
      can predict relapse or refractory disease in 30 histology-proven GPA patients
      with follow-up duration >= 12 weeks. METHODS: We reviewed the medical records of
      30 GPA patients. We collected clinical data, ANCAs, BVAS for GPA, FFSs at
      diagnosis, and we compared variables between the two groups based on relapse or
      refractory disease. The optimal cut-offs were extrapolated. Multivariate logistic
      regression and Cox hazard model analyses were conducted to identify predictors of
      refractory disease. RESULTS: The mean age and follow-up duration of patients were
      63.3 years old and 45.2 months. The mean initial BVAS for GPA, FFS (1996) and FFS
      (2009) were 5.4, 0.6 and 1.0. There were no significant predictors of relapse.
      The mean BVAS for GPA, FFS (1996) and FFS (2009) of patients with refractory
      disease were higher than those without (P < 0.05 for all). Patients having BVAS
      for GPA >= 9.5, FFS (1996) >= 2 and FFS (2009) >= 2 exhibited significantly
      enhanced risk of refractory disease than those without (relative risk 23.0, 11.0,
      and 55.0, respectively), and low cumulative refractory disease-free survival
      rates. Multivariate Cox hazard model analysis proved BVAS for GPA >= 9.5 was an
      independent predictor of refractory disease during the follow-up duration (odds
      ratio 12.892). CONCLUSION: BVAS for GPA >= 9.5 was an independent predictor of
      refractory disease during follow-up duration >= 12 weeks.

PMID- 28766858
TI  - Adolescent presentations to an adult hospital emergency department.
AB  - OBJECTIVE: Age-related policies allow adolescents to access paediatric and adult
      EDs. Anecdotally, paediatric and adult EDs report challenges when caring for
      older and younger adolescents, respectively. Our aim was to describe the
      characteristics of an adolescent population attending an adult ED, co-located
      with a tertiary paediatric ED. METHODS: The Westmead Hospital ED database was
      accessed for 14.5-17.9 years old presentations between January 2010 and December
      2012. Patient diagnosis coding (SNOMED) was converted to ICD-10. De-identified
      data were transferred into Microsoft Excel with analysis performed using spss
      V22. RESULTS: There were 5718 presentations made to the Westmead Hospital,
      Sydney, Australia ED by 4450 patients, representing 3.3% (95% CI 3.2-3.4) of
      total visits from all patients 14.5 years and above. The mean age of the sample
      was 16.6 years (male 51.8%). Presentations triaged as level 4 or 5 represented
      61.0% (95% CI 58.7-61.3) of visits. The proportion of patients who did not wait
      to receive care was 13.8% (95% CI 12.9-14.7), which was significantly higher than
      adult rates (P < 0.01). There were 279 unscheduled return visits (visits made <72
      h of discharge) representing 4.9% (95% CI 4.4-5.8) of all presentations. Injury
      was the most common diagnosis (30.2%, 95% CI 28.8-31.6). Chronic physical illness
      and alcohol-related visits comprised 2.1% (95% CI 1.7-2.5) and 0.8% (95% CI 0.6
      1.0) of adolescent presentations, respectively. CONCLUSION: Contrary to reported
      staff perceptions, adolescent chronic physical illness presentations were not a
      major burden. Alcohol was likely under-recorded as a contributing factor to
      presentations.

PMID- 28766859
TI  - Transulnar cardiac catheterization and percutaneous coronary intervention:
      techniques, transradial comparisons, anatomical considerations, and comprehensive
      literature review.
AB  - Ulnar arterial access for cardiac catheterization and intervention is an
      alternative approach compared with radial or femoral access. Ulnar access is
      infrequently performed since the radial artery is readily palpable and is
      commonly used worldwide to minimize vascular complications from femoral access.
      Nevertheless, ulnar access provides a suitable access site in patients who are
      poor candidates for femoral access, have pre-existing radial occlusion, radial
      artery hypoplasia or hyperplasia from prior radial artery procedures, radial
      stenosis, radial loops, radial tortuosity, small radial arteries, and/or have
      future need for radial graft for dialysis or coronary artery bypass graft.
      Furthermore, femoral access is the standard default option if radial access
      fails. Consequently, learning ulnar access provides a suitable forearm
      alternative to avoid femoral access when deemed high risk or undesirable. This
      review discusses the techniques of ulnar access, advantages and disadvantages of
      ulnar versus radial access, the clinical trials on ulnar cardiac catheterization
      and its associated complications.

PMID- 28766860
TI  - Hydroarylation of 2-Aryloxybut-1-en-3-ynes via Pd/Acid-Catalyzed C-H Bond
      Activation: A Concise Synthesis of 2,3-Bismethylene-2,3-dihydrobenzofurans.
AB  - An intramolecular exo-hydroarylation of 2-aryloxy-1,4-disilylbut-1-en-3-ynes via
      ortho-C-H bond activation under palladium(0) and acid catalysis was found to give
      2,3-bis(silylmethylidene)-2,3-dihydrobenzofurans. The two silyl groups present
      probably promoted the reaction and played a key role in stabilizing the diene
      moiety in the product. The products readily led to functionalized condensed
      cycles by a Diels-Alder reaction.

PMID- 28766862
TI  - Inhibition of Protein-Protein Interactions: New Options for Developing Drugs
      against Neglected Tropical Diseases.
AB  - Wake up! Sleeping sickness and Chagas disease are neglected tropical diseases
      caused by trypanosome infections. Small molecules that disrupt a crucial protein
      protein interaction in the parasites offer a new approach to drug development for
      these diseases.

PMID- 28766861
TI  - Overexpression of NRF2 is correlated with prognoses of patients with
      malignancies: A meta-analysis.
AB  - BACKGROUND: Previous published research has demonstrated that NRF2 expression is
      a poor prognostic factor for many malignancies. However, because of the small
      sample enrolled in a single study, it is difficult to draw valuable conclusions.
      Therefore, we hypothesized that NRF2 overexpression in cancer tissues may be
      associated with the prognoses of patients with solid malignancies, and conducted
      a systemic review and meta-analysis. METHODS: A comprehensive search of PubMed,
      Web of Science, Science Direct, Embase, and Ovid databases for relevant studies
      regarding the role of NRF2 expression in solid malignancies was conducted. Hazard
      ratios (HR) and 95% confidence intervals (CIs) were extracted from these studies
      to provide pooled estimates of the effect of NRF2 expression on patients' overall
      and disease-free survival. RESULTS: Nine studies met the criteria for analysis.
      Statistical analysis demonstrated that compared to patients with low NRF2
      expression, patients with overexpression of NRF2 had poorer overall survival (HR
      2.01, 95% CI 1.57-2.56; P < 0.001) and disease-free survival (HR 3.25, 95% CI
      1.29-8.15; P = 0.025). CONCLUSION: Published evidence of the role of NRF2
      expression in survival of cancer patients is limited. This analysis supports the
      view that NRF2 overexpression is a poor prognostic factor for solid malignancies,
      thus optimizing treatment for patients with NRF2 overexpression may improve their
      overall survival.

PMID- 28766863
TI  - Do storybooks with anthropomorphized animal characters promote prosocial
      behaviors in young children?
AB  - For millennia, adults have told children stories not only to entertain but also
      to impart important moral lessons to promote prosocial behaviors. Many such
      stories contain anthropomorphized animals because it is believed that children
      learn from anthropomorphic stories as effectively, if not better than, from
      stories with human characters, and thus are more inclined to act according to the
      moral lessons of the stories. Here we experimentally tested this belief by
      reading preschoolers a sharing story with either human characters or
      anthropomorphized animal characters. Reading the human story significantly
      increased preschoolers' altruistic giving but reading the anthropomorphic story
      or a control story decreased it. Thus, contrary to the common belief, realistic
      stories, not anthropomorphic ones, are better for promoting young children's
      prosocial behavior.

PMID- 28766864
TI  - Investigation of Chemical Bonding in In Situ Cryocrystallized Organometallic
      Liquids.
AB  - This Communication presents the crystal structure of the organometallic complexes
      (eta4 -1,3-cyclohexadiene) iron tricarbonyl (I) and (methyl cyclopentadienyl)
      manganese tricarbonyl (II) which are both liquid at room temperature. The crystal
      structures were determined using a state-of-the-art in situ cryocrystallization
      technique. The bonding features were elucidated using topological analysis of
      charge density in the framework of quantum theory of atoms in molecules (QTAIM)
      and theoretical charge density analysis (multipolar refinement), to decipher the
      metal-carbonyl, metal-olefin and metal-carbocyclic ligand interactions in these
      complexes. Complex I displayed a simultaneous interplay of a "synergic effect"
      (sigma-donation and pi-back-bonding in the metal and an end-on coordinated
      carbonyl interaction) as well as consistency with the Dewar-Chatt-Duncanson (DCD)
      model (metal and side-on coordinated pi-ligand interactions).

PMID- 28766865
TI  - Trapping as retrieval technique to resolve a ruptured and entrapped coronary
      balloon catheter.
AB  - A 69 year old male, with a previous percutaneous revascularization of the mid
      circumflex with a bare metal stent in 2007 was admitted to our centre for
      unstable angina. The angiography showed a severely calcified coronary tree with a
      functionally severe plaque on the proximal left anterior descending artery (LAD)
      and a critical focal lesion on the proximal right coronary artery. After a high
      pressure predilation on the proximal LAD, the balloon ruptured causing a
      retrograde LAD-left main (LM) dissection that was rapidly sealed with three
      overlapping zotarolimus-eluting stents from medial LAD to LM. We then used a new
      non-compliant balloon for successive aggressive postdilation. After a difficult
      handling, when the balloon catheter was pulled out of the body and we realized
      that the tip and membranous part of the balloon-catheter was separated from the
      rest, and entangled at the LM. After a first approach to retrieve the dislodged
      balloon with a snare, the ruptured balloon was successfully removed by trapping
      and withdrawing the whole system, including the guiding catheter and the wire.

PMID- 28766866
TI  - Enhanced Oral Bioavailability of Diltiazem by the Influence of Gallic Acid and
      Ellagic Acid in Male Wistar Rats: Involvement of CYP3A and P-gp Inhibition.
AB  - The oral bioavailability of diltiazem is very low due to rapid first pass
      metabolism in liver and intestine. The purpose of the study was to investigate
      the effect of gallic acid and ellagic acid on intestinal transport and oral
      bioavailability of diltiazem in rats. The intestinal transport and permeability
      of diltiazem was evaluated by in vitro non-everted sac method and in situ single
      pass intestinal perfusion study. The oral pharmacokinetics was evaluated by
      conducting oral bioavailability study. The intestinal transport and apparent
      permeability of diltiazem were significantly enhanced in duodenum, jejunum, and
      ileum of gallic and ellagic acid-treated groups. The effective permeability of
      diltiazem was significantly enhanced in ileum part of gallic and ellagic acid
      treated groups. When compared with control group, the presence of these two
      phytochemicals significantly enhanced the area under plasma concentration-time
      curve and the peak plasma concentration of diltiazem (Cmax ). Gallic acid and
      ellagic acid significantly increased the bioavailability of diltiazem due to the
      inhibition of both CYP3A-mediated metabolism and P-glycoprotein-mediated efflux
      in the intestine and/or liver. Based on these results, the clinical experiments
      are warranted for the confirmation to reduce the dose of diltiazem when
      concomitantly administered with these phytochemicals. Copyright (c) 2017 John
      Wiley & Sons, Ltd.

PMID- 28766867
TI  - Does Temperament Underlie Infant Novel Food Responses?: Continuity of Approach
      Withdrawal From 6 to 18 Months.
AB  - This study investigated whether temperamental approach-withdrawal underlies
      infants' responses to novel foods. Data were drawn from a longitudinal study of
      mother-infant dyads (n = 136). Approach-withdrawal responses to novel foods and
      novel toys were coded when infants were 6 and 12 months of age. When infants were
      18 months of age, approach-withdrawal behaviors, positive affect, and negative
      affect were used in a latent profile analysis to identify groups of toddlers who
      exhibited similar responses to novelty. As predicted, novel food and novel toy
      responses were concurrently associated at 12 months and followed a similar
      developmental pattern across the 1st year. Furthermore, novel food acceptance at
      12 months of age, but not 6 months, predicted greater toddler approach.

PMID- 28766868
TI  - Markovnikov-Selective Palladium Catalyst for Carbonylation of Alkynes with
      Heteroarenes.
AB  - A new class of palladium catalysts, based on heterocyclic diphosphines, was
      rationally designed and synthesized. Application of one of these catalysts allows
      novel Markovnikov-selective carbonylation of non-activated alkynes with
      heteroarenes to give the corresponding branched alpha,beta-unsaturated ketones in
      excellent yields (up to 97 %) and regioselectivities (b/l up to 99:1). In
      addition to heteroarenes, other common nucloephiles (alcohol, phenol, amine, and
      amide) furnish the desired carbonylation products smoothly in high yields.

PMID- 28766870
TI  - Extracellular Hyaluronic Acid Influences the Efficacy of EGFR Tyrosine Kinase
      Inhibitors in a Biomaterial Model of Glioblastoma.
AB  - 3D biomaterial models have potential to explore the influence of the tumor
      microenvironment on aberrant signaling pathways and compensatory signals using
      patient-derived cells. Glioblastoma (GBM) tumors are highly heterogeneous, with
      both cell composition and extracellular matrix biophysical factors seen as key
      regulators of malignant phenotype and treatment outcomes. Amplification,
      overexpression, and mutation of the epidermal growth factor receptor (EGFR)
      tyrosine kinase have been identified in 50% of GBM patients. Here, hyaluronic
      acid (HA) decorated methacrylamide-functionalized gelatin (GelMA) hydrogels are
      used to examine the synergies between microenvironmental factors and a model EGFR
      tyrosine kinase inhibitor (TKI) using patient-derived xenograft cells. The in
      vitro behavior of 3 patient-derived xenografts that reflect a clinically relevant
      range of EGFR variants is characterized: GBM10 (EGFR, wild type), GBM12 (EGFR+),
      and GBM6 (EGFRvIII). GelMA hydrogels support xenograft culture; cells remain
      viable, active, respond to matrix-immobilized HA, and upregulate genes associated
      with matrix remodeling and tumor growth. Interestingly, matrix-immobilized HA
      alters the response of GBM cells to a model tyrosine kinase inhibitor, erlotinib.
      While constitutively activated EGFRvIII cells are sensitive to TKI in gelatin
      hydrogels, hyaluronic acid mediated adhesive signaling interacts with EGFRvIII
      signaling to increase cell metabolic activity, increase soluble hyaluronic acid
      synthesis, and modify response to erlotinib exposure.

PMID- 28766871
TI  - Prevalence and antimicrobial resistance among Escherichia coli and Salmonella in
      Ontario smallholder chicken flocks.
AB  - Surveillance is an important component of an overall strategy to address
      antimicrobial resistant bacteria in food animals and the food chain. The poultry
      market has many points of entry into the Canadian food chain, and some production
      practices are underrepresented in terms of surveillance. For example, pathogen
      carriage and antimicrobial resistance surveillance data are limited in
      smallholder chicken flocks raised for slaughter at provincially inspected
      abattoirs. In Canada, antimicrobial resistance in Escherichia coli and Salmonella
      isolated from commercial broiler chicken flocks, slaughtered at federally
      inspected abattoirs, is monitored by the Canadian Integrated Program for
      Antimicrobial Resistance Surveillance (CIPARS). The objective of this study was
      to establish baseline information of antimicrobial resistance presence in E. coli
      and Salmonella isolated from smallholder flocks in Ontario, utilizing CIPARS
      collection and isolation methodologies, and to compare findings with CIPARS
      federally inspected abattoir data from Ontario, Canada. Five chickens per flock
      were sampled from 205 smallholder flocks. Of 1,025 samples, the E. coli
      prevalence was 99% (1,022/1,025), and 47% (483/1,022) of positive E. coli
      isolates were resistant to one or more of the 14 antimicrobials. Furthermore, as
      compared to results reported for the CIPARS commercial flocks, E. coli isolates
      from smallholder flocks had significantly lower resistance prevalence to six of
      14 individual antimicrobials. Recovery of E. coli did not differ between
      federally inspected and provincially inspected flocks. Salmonella prevalence at
      the bird level in smallholder flocks was 0.3% (3/1,025), significantly lower (p ?
      0.0001, 95% CI 0.080%-0.86%) than federally inspected commercial flocks. The
      overall differences found between the commercial and smallholder flocks may be
      explained by differences in poultry husbandry practices and hatchery sources.

PMID- 28766872
TI  - Population-based case-control study of the association between weather-related
      extreme heat events and neural tube defects.
AB  - BACKGROUND: Elevated body core temperature has been shown to have teratogenic
      effects in animal studies. Our study evaluated the association between weather
      related extreme heat events (EHEs) in the summer season and neural tube defects
      (NTDs), and further investigated whether pregnant women with a high
      pregestational body mass index (BMI) have a greater risk of having a child with
      NTDs associated with exposure to EHE than women with a normal BMI. METHODS: We
      conducted a population-based case-control study among mothers of infants with
      NTDs and mothers of infants without major birth defects, who participated in the
      National Birth Defects Prevention Study and had at least 1 day of the third or
      fourth week postconception during summer months. EHEs were defined using the 95th
      and the 90th percentiles of the daily maximum universal apparent temperature.
      Adjusted odds ratios and 95% confidence intervals were calculated using
      unconditional logistic regression models with Firth's penalized likelihood method
      while controlling for other known risk factors. RESULTS: Overall, we did not
      observe a significant association between EHEs and NTDs. At the climate region
      level, consistently elevated but not statistically significant estimates were
      observed for at least 2 consecutive days with daily universal apparent maximum
      temperature above the 95th percentile of the UATmax distribution for the season,
      year, and weather monitoring station in New York (Northeast), North Carolina and
      Georgia (Southeast), and Iowa (Upper Midwest). No effect modification by BMI was
      observed. CONCLUSION: EHEs occurring during the relevant developmental window of
      embryogenesis do not appear to appreciably affect the risk of NTDs. Future
      studies should refine exposure assessment, and more completely account for
      maternal activities that may modify the effects of weather exposure. Birth
      Defects Research 109:1482-1493, 2017.(c) 2017 Wiley Periodicals, Inc.

PMID- 28766874
TI  - People with dementia in the emergency department: Behavioural symptoms and use of
      restraint.

PMID- 28766873
TI  - Analysis of nifH-RNA reveals phylotypes related to Geobacter and Cyanobacteria as
      important functional components of the N2 -fixing community depending on depth
      and agricultural use of soil.
AB  - In this survey, a total of 80 787 reads and 28 171 unique NifH protein sequences
      were retrieved from soil RNA. This dataset extends our knowledge about the
      structure and diversity of the functional diazotrophic communities in
      agricultural soils from Argentinean Pampas. Operational taxonomic unit (OTU)
      based analyses showed that nifH phylotypes related to Geobacter and
      Anaeromyxobacter (44.8%), Rhizobiales (29%), Cyanobacteria (16.7%), and
      Verrucomicrobiales (8%) are key microbial components of N2 fixation in soils
      associated with no-till management and soil depth. In addition, quantification of
      nifH gene copies related to Geobacter and Cyanobacteria revealed that these
      groups are abundant in soils under maize-soybean rotation and soybean
      monoculture, respectively. The correlation of physicochemical soil parameters
      with the diazotrophic diversity and composition showed that soil stability and
      organic carbon might contribute to the functional signatures of particular nifH
      phylotypes in fields under no-till management. Because crop production relies on
      soil-borne microorganism's activities, such as free N2 fixation, the information
      provided by our study on the diazotrophic population dynamics, associated with
      the edaphic properties and land-use practices, represents a major contribution to
      gain insight into soil biology, in which functionally active components are
      identified.

PMID- 28766875
TI  - Species Differences in Renal Development and Associated Developmental
      Nephrotoxicity.
AB  - The developing kidney is sensitive to both morphological and functional
      disturbances during the gestational and postnatal phases of growth and
      differentiation. Exposure to drugs or chemicals during these critical windows of
      renal development can result in aplasia, dysplasia, polycystic kidney disease,
      hydronephrosis, or other features characteristic of nephrotoxicity, including
      tubule dilation, necrosis, or mineralization. Functional effects can occur
      without associated morphological abnormalities. Differences in the timing of
      nephrogenesis and morphologic renal development among species help to explain
      specific phenotypes of various gestational and postnatal teratogens and
      nephrotoxins. Functional maturation follows anatomical maturation, but important
      differences in maximally achieved glomerular filtration rate, concentrating
      ability and acid-base equilibrium between species makes comparison of these
      timings critical for accurate and consistent translation of laboratory animal
      toxicity data to the human clinical experience. Species and age dependent
      differences in the maturation of kidney transporters, renal xenobiotic metabolism
      and renal blood flow can have a profound effect on the toxicity profiles of
      agents and marked differences in the tolerability based on age. Advances in the
      understanding of the genetics of inherited renal diseases and the underlying
      cellular and molecular pathogenesis of renal developmental anomalies has helped
      provide mechanistic understanding of many teratogenic and perinatal nephrotoxic
      agents. Investigative studies have provided important translational and
      mechanistic information for assessing human pediatric nephrotoxic potential.
      Birth Defects Research 109:1243-1256, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28766876
TI  - Simulation-based education leads to decreased use of fluoroscopy in diagnostic
      coronary angiography.
AB  - OBJECTIVES: The aim of this study is to determine whether simulation-based
      education (SBE) translates into reduced procedure time, radiation, and contrast
      use in actual clinical care. BACKGROUND: As a high volume procedure often
      performed by novice cardiology fellows, diagnostic coronary angiography
      represents an excellent target for SBE. Reports of SBE in interventional
      cardiology are limited and there is little understanding of the potential
      downstream clinical impact of these interventions. METHODS: All diagnostic
      coronary angiograms performed at a single center between January 1, 2011 and June
      30, 2015 were analyzed. Random effects linear regression models were used to
      compare outcomes between procedures performed by 12 cardiology fellows who
      underwent simulation-based training and those performed by 20 traditionally
      trained fellows. RESULTS: Thirty-two cardiology fellows performed 2,783
      diagnostic coronary angiograms. Procedures performed by fellows trained with SBE
      were shorter (mean of 23.98 min vs. 24.94 min, P = 0.034) and were performed with
      decreased radiation (mean of 56,348 mGycm2 vs. 66,120 mGycm2 , P < 0.001). After
      controlling for year in training, procedure year, access site, and supervising
      attending physician, training on the simulator was independently associated with
      117 fewer seconds of fluoroscopy time per procedure (P = 0.04). CONCLUSIONS:
      Diagnostic coronary angiography SBE is associated with decreased use of
      fluoroscopy in downstream clinical care. SBE may be a useful tool to reduce
      radiation exposure in the cardiac catheterization laboratory.

PMID- 28766877
TI  - Munchausen by Proxy: A Qualitative Investigation into Online Perceptions of
      Medical Child Abuse.
AB  - In Munchausen by proxy (MBP) maltreatment, increasingly termed "medical child
      abuse" (MCA), a caregiver fabricates or induces illness in another. The
      perpetrator's goal for the behavior is to meet personal emotional needs by
      forcing unnecessary or misguided medical or psychological treatment. Generally, a
      mother is the perpetrator and her child is the victim. There is a serious lack of
      research into most aspects of MCA, and this study is the first to utilize the
      anonymity of an Internet forum to investigate victims' first-hand experiences of,
      and the public's opinions about, suspected and confirmed MCA. Three-hundred and
      fifty-six posts by 348 members were explored and coded using formal qualitative
      content analysis. By accessing an open-thought online forum, this paper acquired
      information regarding social perceptions about the nonperpetrating partners who
      are unaware of the maltreatment; the disturbing and counterintuitive phenomenon
      of MCA itself; and the resistance often faced by those who attempt to report it.

PMID- 28766878
TI  - Women's dietary diversity in rural Bangladesh: Pathways through women's
      empowerment.
AB  - The relationship between women's empowerment and women's nutrition is
      understudied. We aimed to elucidate this relationship by quantifying possible
      pathways between empowerment and dietary diversity among women in rural
      Bangladesh. In 2015, we conducted a cross-sectional survey of 2,599 married women
      ages 15-40 (median: 25) living in 96 settlements of Habiganj District,
      Bangladesh, as a baseline for the Food and Agricultural Approaches to Reducing
      Malnutrition trial. We collected data on women's empowerment (highest completed
      grade of schooling and agency), dietary diversity, and demographic factors,
      including household wealth. We used exploratory factor analysis and confirmatory
      factor analysis on random split-half samples, followed by structural equation
      modelling, to test pathways from schooling, through domains of women's agency, to
      dietary diversity. Factor analysis revealed 3 latent domains of women's agency:
      social solidarity, decision-making, and voice with husband. In the adjusted
      mediation model, having any postprimary schooling was positively associated with
      voice with husband (beta41  = .051, p = .010), which was positively associated
      with dietary diversity (beta54  = .39, p = .002). Schooling also had a direct
      positive association with women's dietary diversity (beta51  = .22, p < .001).
      Neither women's social solidarity nor decision-making mediated the relationship
      between schooling and dietary diversity. The link between schooling and dietary
      diversity was direct and indirect, through women's voice with husband but not
      through women's social solidarity or decision-making. In this population, women
      with postprimary schooling seem to be better able to negotiate improved diets for
      themselves.

PMID- 28766879
TI  - Bivalirudin in percutaneous coronary intervention for chronic total occlusion: A
      single-center pilot study.
AB  - BACKGROUND: Bivalirudin has been reported to be an alternative to unfractionated
      heparin (UFH) for anticoagulation during percutaneous coronary intervention (PCI)
      and associated with less bleeding risk. However, the feasibility of bivalirudin
      during PCI of chronic total occlusion lesions (CTO) remains unknown. OBJECTIVE:
      To evaluate the efficacy and safety of bivalirudin versus UFH in CTO PCI.
      METHODS: In this prospective and randomized controlled trial in single center,
      CTO patients with high bleeding risk were randomized to treatment with
      bivalirudin (bolus 0.75 mg/kg followed by infusion of 1.75, extra bolus 0.3 mg/kg
      before stenting) or UFH (100 IU/kg). The primary efficacy end point was the
      incidence of major adverse cardiac events (MACEs, composite of all-cause
      mortality, cardiac death, stent thrombosis, periprocedural myocardial infarction,
      or additional unplanned target lesion revascularization, or any other post-PCI
      ischemic event) in-hospital, and at 1-year follow-up. The primary safety end
      point was the occurrence of any bleeding or entry-site complications after PCI.
      RESULTS: A total of 84 high bleeding risk patients undergoing PCI for CTO lesions
      were enrolled. The baseline characteristics were similar in both treatment arms.
      In hospital MACEs rates were 21.4% in the bivalirudin group and 14.3% in the UFH
      group (P = 0.393). During 1-year's follow-up, end points did not significantly
      differ between the groups either. Occurrence of the major bleeding events were
      4.8% in the bivalirudin group and 9.5% in the UFH group (P = 0.676). No entry
      site complication was observed. CONCLUSION: In CTO patients at high risk for
      bleeding undergoing PCI, our data indicates that bivalirudin appears to be at
      least comparable in efficacy and safety to UFH. A larger clinical trial should be
      designed to further elucidate its efficacy and safety.

PMID- 28766882
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 33/2017.

PMID- 28766880
TI  - MMP-2 and MMP-13 affect vasculogenic mimicry formation in large cell lung cancer.
AB  - Matrix metalloproteinases (MMPs) have critical functions in tumour vasculogenic
      mimicry (VM). This study explored the mechanisms underlying MMP-13 and MMP-2
      regulation of tumour VM formation in large cell lung cancer (LCLC). In our study,
      laminin5 (Ln-5) fragments cleaved by MMP-2 promoted tubular structure formation
      by the LCLC cell lines H460 and H661 in three-dimensional (3D) cultures.
      Transient up-regulation of MMP-13 or treatment with recombinant MMP-13 protein
      abrogated tubular structure formation of H460 cells in 3D culture. Treated cells
      with Ln-5 fragments cleaved by MMP-2 stimulated EGFR and F-actin expression. Ln-5
      fragments cleaved by MMP-13 decreased EGFR/F-actin expression and disrupted VM
      formation. MMP-13 expression was negatively correlated with VM, Ln-5 and EGFR in
      LCLC tissues and xenograft. In vivo experiments revealed that VM was decreased
      when the number of endothelium-dependent vessels (EDVs) increased during
      xenograft tumour growth, whereas MMP-13 expression was progressively increased.
      In conclusion, MMP-2 promoted and MMP-13 disrupted VM formation in LCLC by
      cleaving Ln-5 to influence EGFR signal activation. MMP-13 may regulate VM and EDV
      formation.

PMID- 28766881
TI  - Angiographic and clinical performance of polymer-free biolimus-eluting stent in
      patients with ST-segment elevation acute myocardial infarction in a metropolitan
      public hospital: The BESAMI MUCHO study.
AB  - OBJECTIVES: This study aimed at assessing the performance of a new generation
      polymer-free biolimus-eluting stent (BES) in real-world patients with ST-segment
      elevation myocardial infarction (STEMI). BACKGROUND: Polymers components of early
      generation drug-eluting stents have been implicated in the pathogenesis of
      delayed arterial healing, vessel remodeling, and delayed stent thrombosis.
      Recently, a novel polymer-free BES has shown excellent clinical performance in
      clinical trial setting. METHODS: Overall, 175 consecutive patients (64 +/- 14
      years, 141 men) treated with the BioFreedom (Biosensors Europe, Morges,
      Switzerland) polymer-free BES because of STEMI were included in this study. The
      primary endpoint was the rate of major adverse cardiac events (MACE), a composite
      of cardiac death, recurrent myocardial infarction, and ischemia-driven target
      vessel revascularization at 1 year follow-up. A subgroup of patients underwent 6
      month angiographic follow-up. Dual antiplatelet therapy was prescribed for 12
      months after STEMI. RESULTS: At 1 year, the cumulative rate of MACE was 4.6%. One
      patient (0.6%) had an arrhythmic cardiac death and five (2.9%) had ischemia
      driven target vessel revascularization, although only three (1.7%) had target
      lesion revascularization. Two (1.1%) patients had acute stent thrombosis yielding
      nonfatal myocardial infarction. In 70 patients (63 +/- 14 years, 61 men),
      quantitative coronary angiography at 6-month follow-up revealed diameter stenosis
      of 24.1 +/- 13.7% and minimal lumen diameter of 2.29 +/- 0.56 mm, yielding a late
      lumen loss of 0.13 +/- 0.14 mm. CONCLUSIONS: In real-world setting, implantation
      of a new-generation polymer-free BES during STEMI is associated with favorable
      clinical and angiographic results, pointing toward the overall efficacy and
      safety of the device in complex clinical scenarios.

PMID- 28766883
TI  - Identification of sentinel lymph nodes by contrast-enhanced ultrasonography with
      Sonazoid in patients with breast cancer: a feasibility study in three hospitals.
AB  - The aim of this prospective study was to evaluate the feasibility of periareolar
      injection of the contrast agent Sonazoid (SNZ) followed by ultrasonography (US)
      for the identification of sentinel lymph node (SLN) in breast cancer patients
      with clinically negative node. Patients (n = 100) with T1-2N0M0 breast cancer
      received a periareolar injection of SNZ followed by US to identify contrast
      enhanced SLN. Each contrast-enhanced SLN underwent fine needle aspiration
      cytology (FNAC) followed by SLN biopsy with a conventional method using blue dye
      and/or radiocolloid (B/R). In almost all cases, contrast-enhanced lymphatic
      vessels were clearly visualized by US soon after the periareolar injection of SNZ
      and the SLNs were easily identified with an identification rate of 98% (98/100)
      for SNZ and 100% (100/100) for B/R. The number of SLNs identified by SNZ (SNZ
      SLN) (mean per patient, 1.52) was significantly lower than that identified by B/R
      (B/R-SLN) (2.19) (P < 0.0001). Twenty-five patients with positive SLNs had at
      least one positive SNZ-SLN. On a node-by-node basis, sensitivity, specificity,
      and accuracy of FNAC for SNZ-SLNs (n = 149) were 33.3%, 99.2%, and 85.9%,
      respectively. Identification of SLN by periareolar injection of SNZ is a
      technically simple method with an identification rate as high as 98%. SNZ-SLN
      thus seems to be a good target for FNAC, but sensitivity of FNAC for SNZ-SLNs
      needs to be improved.

PMID- 28766884
TI  - Risk factors for orofacial clefts in India: A case-control study.
AB  - BACKGROUND: Orofacial clefts (OFC) are linked with several genetic and
      environmental factors. The aim of this study was to explore the association of
      potential risk factors with OFCs in India. METHODS: This was a hospital-based,
      matched case-control (1:4 ratio; matching done for parity) study conducted in
      Hyderabad, Bengaluru, and Delhi-National Capital Region. Cases (nonsyndromic
      clefts) were recruited from treatment centers, while controls (live births) were
      recruited from maternity centers. Information on exposures was collected during
      personal interviews. Exposures of interest included folic acid supplementation
      during the peri-conceptional period, consanguineous marriage, exposure to drugs,
      infections during pregnancy, family history of OFC, and dietary factors. RESULTS:
      A total of 785 participants were included in the study: 157 cases and 628
      controls. A family history of cleft lip/palate (adjusted odds ratio [AOR], 15.48;
      95% confidence interval [CI], 4.36-54.96; p value = 0.001), exclusive
      vegetarianism (AOR, 4.47; 95% CI, 1.83-10.98; p value = 0.001), and delayed first
      conception (AOR, 2.55, 95% CI, 1.25-5.21, p = 0.01) were found to be strongly
      associated with higher risk of OFCs. Supplementation with folic acid during first
      3 months of pregnancy was not found to be protective against OFCs (AOR, 1.24; 95%
      CI, 0.59-2.58; p value = 0.56). CONCLUSION: Our study confirmed the importance of
      family history as a risk factor for OFC. Our study did not show an association
      with folic acid supplementation but was underpowered to detect small effects. Our
      finding of higher risk among vegetarians requires replication. Birth Defects
      Research 109:1284-1291, 2017. (c) 2017 The Authors. Birth Defects Research
      Published by Wiley Periodicals, Inc.

PMID- 28766885
TI  - Technical Note: Construction of heterogeneous head phantom for quality control in
      stereotactic radiosurgery.
AB  - PURPOSE: Stereotactic radiosurgery is a high precision modality for conformally
      delivering high doses of radiation to the brain lesion with a large dose volume.
      Several studies for the quality control of this technique were performed to
      measure the dose delivered to the target with a homogenous head phantom and some
      dosimeters. Some studies were also performed with one or two instances of
      heterogeneity in the head phantom to measure the dose delivered to the target.
      But these studies assumed the head as a sphere and simple shape heterogeneity.
      The construction of an adult human head phantom with the same size, shape, and
      real inhomogeneity as an adult human head is needed. Only then is measuring the
      accurate dose delivered to the area of interest and comparison with the
      calculated dose possible. METHODS: According to the ICRU Report 44,
      polytetrafluoroethylene (PTFE) and methyl methacrylate were selected as a bone
      and soft tissue, respectively. A set of computed tomography (CT) scans from a
      standard human head were taken, and simplification of the CT images was used to
      design the layers of the phantom. The parts of each slice were cut and attached
      together. Tests of density and CT number were done to compare the material of the
      phantom with tissues of the head. The dose delivered to the target was measured
      with an EBT3 film. RESULTS: The density of the PTFE and Plexiglas that were
      inserted in the phantom are in good agreement with bone and soft tissue. Also,
      the CT numbers of these materials have a low difference. The dose distribution
      from the EBT3 film and the treatment planning system is similar. CONCLUSIONS: The
      constructed phantom with a size and inhomogeneity like an adult human head is
      suitable to measure the dose delivered to the area of interest. It also helps
      make an accurate comparison with the calculated dose by the treatment planning
      system. By using this phantom, the actual dose delivered to the target was
      obtained. This anthropomorphic head phantom can be used in other modalities of
      radiosurgery as well.

PMID- 28766887
TI  - A cost analysis of individualized asparaginase treatment in pediatric acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Therapeutic drug monitoring (TDM) of asparaginase is necessary to
      respond to variability in asparaginase activity levels, detect silent
      inactivation, and distinguish between real allergies and allergic-like reactions
      with and without asparaginase neutralization, respectively. In this study, the
      costs of an individualized and fixed asparaginase dosing schedule were compared.
      PROCEDURE: Patients, treated according to the Dutch Childhood Oncology Group ALL
      11 protocol (individualized PEGasparaginase treatment, starting dose: 1,500 IU/m2
      ) or ALL-10 protocol (native Escherichia coli asparaginase followed by 2,500
      IU/m2 PEGasparaginase), were included. To focus on TDM of PEGasparaginase, the
      costs were also calculated excluding patients treated with Erwinia asparaginase
      and compared to a hypothetical protocol with a fixed dose of 1,500 IU/m2
      PEGasparaginase. Direct asparaginase-related medical costs, including costs for
      asparaginase use (calculated with the absolute dose), TDM, laboratory tests,
      daycare treatment, and outpatient clinic visits, were calculated. RESULTS: Eighty
      three ALL-10 patients and 51 ALL-11 patients were included. The asparaginase
      related costs were 30.8% lower in ALL-11 than in ALL-10 ($29,048 vs. $41,960).
      The ALL-11 costs of nonallergic patients were 20.4% lower, when using TDM, than
      the hypothetical protocol with a fixed dose of 1,500 IU/m2 ($13,178 vs. $16,551).
      TDM accounted for 12.4% of the costs. Including asparaginase waste, TDM in ALL-11
      will be cost saving if three doses can be prepared out of one vial compared to a
      fixed dose of 1,500 IU/m2 . CONCLUSIONS: TDM of asparaginase is cost saving if
      calculated with the absolute asparaginase dose and will be if the waste is
      minimalized by preparing multiple doses out of one vial.

PMID- 28766886
TI  - Small cell lung carcinoma cell line screen of etoposide/carboplatin plus a third
      agent.
AB  - The SCLC combination screen examined a 9-point concentration response of 180
      third agents, alone and in combination with etoposide/carboplatin. The
      predominant effect of adding a third agent to etoposide/carboplatin was
      additivity. Less than additive effects occurred frequently in SCLC lines
      sensitive to etoposide/carboplatin. In SCLC lines with little or no response to
      etoposide/carboplatin, greater than additive SCLC killing occurred over the
      entire spectrum of SCLC lines but never occurred in all SCLC lines. Exposing SCLC
      lines to tubulin-targeted agents (paclitaxel or vinorelbine) simultaneously with
      etoposide/carboplatin resulted primarily in less than additive cell killing. As
      single agents, nuclear kinase inhibitors including Aurora kinase inhibitors,
      Kinesin Spindle Protein/EG5 inhibitors, and Polo-like kinase-1 inhibitors were
      potent cytotoxic agents in SCLC lines; however, simultaneous exposure of the SCLC
      lines to these agents along with etoposide/carboplatin, generally, resulted in
      less than additive cell killing. Several classes of agents enhanced the
      cytotoxicity of etoposide/carboplatin toward the SCLC lines. Exposure of the SCLC
      lines to the MDM2 inhibitor JNJ-27291199 produced enhanced killing in 80% of the
      SCLC lines. Chk-1 inhibitors such as rabusertib increased the cytotoxicity of
      etoposide/carboplatin to the SCLC lines in an additive to greater than additive
      manner. The combination of GSK-3beta inhibitor LY-2090314 with
      etoposide/carboplatin increased killing in approximately 40% of the SCLC lines.
      Exposure to the BET bromodomain inhibitor MK-8628 increased the SCLC cell killing
      by etoposide/carboplatin in 20-25% of the SCLC lines. Only 10-15% of the SCLC
      lines had an increased response to etoposide/carboplatin when simultaneously
      exposed to the PARP inhibitor talazoparib.

PMID- 28766889
TI  - Affordance theory can help understanding of individuals' use of online support
      communities.

PMID- 28766888
TI  - Prevalence of multi-drug resistant organisms in stool of paediatric patients with
      acute leukaemia and correlation with blood culture positivity: A single
      institution experience.
AB  - BACKGROUND: Multi-drug resistant (MDR) bacteria are associated with increased
      morbidity and mortality in children with acute leukaemia. The present study was
      conducted to assess the prevalence of MDR bacteria in stool cultures of patients
      with acute leukaemia at presentation to the hospital. The results were then
      correlated with blood cultures when patients developed septicaemia. PATIENTS AND
      METHODS: The study involved analysis of case records of patients with newly
      diagnosed acute leukaemia less than 18 years of age treated at our centre from
      January 2015 to December 2015. Stool cultures were sent within 72 hr of hospital
      admission and blood cultures were sent when clinically indicated. MDR was defined
      as resistance to at least one antibiotic in three or more following antimicrobial
      groups: cephalosporins, beta-lactam/beta-lactamase inhibitor, carbapenems,
      fluoroquinolones and aminoglycosides. RESULTS: The analysis included 85 patients
      with acute leukaemia, among whom 48 of 85 (56%) patients had positive stool
      cultures and 42 of 85 (50%) patients were positive for MDR bacteria. Blood
      cultures were positive in 13 of 48 patients (27%, seven MDR and six non-MDR) with
      positive stool cultures and three of 37 patients (8%, one MDR and two non-MDR)
      with negative stool cultures (P = 0.01). The concordance between stool and blood
      culture for similar organism was 61%. There were seven deaths in 48 stool culture
      positive patients and two deaths in 37 stool culture negative patients.
      CONCLUSION: This study shows the high prevalence of MDR bacteria in newly
      diagnosed children with acute leukaemia. Colonisation with MDR bacteria in stools
      is associated with increased positivity of blood cultures and mortality.

PMID- 28766890
TI  - iNKT cell activation plus T-cell transfer establishes complete chimerism in a
      murine sublethal bone marrow transplant model.
AB  - Transplant tolerance induction makes it possible to preserve functional grafts
      for a lifetime without immunosuppressants. One powerful method is to generate
      mixed hematopoietic chimeras in recipients by adoptive transfer of donor-derived
      bone marrow cells (BMCs). In our murine transplantation model, we established a
      novel method for mixed chimera generation using sublethal irradiation, CD40-CD40L
      blockade, and invariant natural killer T-cell activation. However, numerous BMCs
      that are required to achieve stable chimerism makes it difficult to apply this
      model for human transplantation. Here, we show that donor-derived splenic T cells
      could contribute to not only the reduction of BMC usage but also the
      establishment of complete chimerism in model mice. By cotransfer of T cells
      together even with one-fourth of the BMCs used in our original method, the
      recipient mice yielded complete chimerism and could acquire donor-specific skin
      allograft tolerance. The complete chimeric mice did not show any remarks of graft
      versus host reaction in vivo and in vitro. Inhibition of the apoptotic signal
      resulted in increase in host-derived CD8+ T cells and chimerism brake. These
      results suggest that donor-derived splenic T cells having veto activity play a
      role in the depletion of host-derived CD8+ T cells and the facilitation of
      complete chimerism.

PMID- 28766891
TI  - Influences of argatroban on five fibrinogen assays.
AB  - INTRODUCTION: Argatroban, as a direct thrombin inhibitor, prolongs the clotting
      time. However, detection of clotting time is the base of routine fibrinogen
      assays, including Clauss method and derived method. The influences of argatroban
      on fibrinogen assays are still unclear. METHODS: Normal pooled plasma (NPP) from
      20 healthy subjects was spiked with increasing argatroban concentrations (0-3.2
      MUg/mL). Then the NPP samples were analyzed by five fibrinogen assays: HemosIL
      Fibrinogen-C XL reagent (Clauss method) on ACL-TOP; STA-Fibrinogen reagent
      (Clauss method) on STA-R Evolution; Siemens Thrombin reagent (Clauss method) on
      CS-5100; SynthASil RecombiPlasTin 2G reagent (PT-derived method) on ACL-TOP; and
      N Antiserum to Human Fibrinogen reagent (NAHF, Immunoassay) on BN2 nephelometer
      analyzer. RESULTS: Argatroban had no influences on NAHF (P=.13). Compared with
      the NAHF, significant reduction was observed on Fibrinogen-C XL (P<.01), while no
      influences were shown on the others (STA-Fibrinogen: P=.41, Siemens Thrombin:
      P=.20, RecombiPlasTin 2G: P=.21) when activated partial thromboplastin time
      (APTT) ratio was no more than 3.0. As APTT ratio was increasing to 4.5, results
      from Clauss and PT-derived methods were significantly lowered (STA-Fibrinogen:
      P=.02, Siemens Thrombin: P<.01, Fibrinogen-C XL: P<.01, RecombiPlasTin 2G:
      P<.01). CONCLUSION: The influences of argatroban on fibrinogen assays differ
      greatly, clinicians should be aware of the influences of argatroban on the
      fibrinogen assays used on site to avoid misdiagnoses.

PMID- 28766892
TI  - Religion and body weight: a review of quantitative studies.
AB  - Increasing interest in relationships between religion and health has encouraged
      research about religion and body weight, which has produced mixed findings. We
      systematically searched 11 bibliographic databases for quantitative studies of
      religion and weight, locating and coding 85 studies. We conducted a systematic
      review, analysing descriptive characteristics of the studies as well as relevant
      religion-body weight associations related to study characteristics. We summarized
      findings for two categories of religion variables: religious affiliation and
      religiosity. For religious affiliation, we found evidence for significant
      associations with body weight in both cross-sectional and longitudinal studies.
      In particular, Seventh-Day Adventists had lower body weight than other
      denominations in cross-sectional analyses. For religiosity, significant
      associations occurred between greater religiosity and higher body weight in both
      cross-sectional and longitudinal studies. In particular, greater religiosity was
      significantly associated with higher body weight in bivariate analyses but less
      so in multivariate analyses. A greater proportion of studies that used a
      representative sample, longitudinal analyses, and samples with only men reported
      significant associations between religiosity and weight. Evidence in seven
      studies suggested that health behaviours and psychosocial factors mediate
      religion-weight relationships. More longitudinal studies and analyses of
      mediators are needed to provide stronger evidence and further elucidate religion
      weight relationships.

PMID- 28766893
TI  - Synthesis of Pinpoint-Fluorinated Polycyclic Aromatic Hydrocarbons: Benzene Ring
      Extension Cycle Involving Microwave-Assisted SN Ar Reaction.
AB  - Fluoroarenes bearing no electron-withdrawing groups (non-activated fluoroarenes)
      readily underwent nucleophilic aromatic substitution with alpha-cyanocarbanions
      under microwave irradiation. The sequence (i) formylalkylation involving the
      cyanoalkylation of fluoroarenes, (ii) difluorovinylidenation, and (iii) Friedel
      Crafts-type cyclization, afforded extended fluoroarenes by one benzene ring per
      cycle. Furthermore, the performance of multiple cycles successfully provided
      higher-order pinpoint-fluorinated polycyclic aromatic hydrocarbons (F-PAHs).

PMID- 28766894
TI  - Recurrent urinary tract infections and low secretory IgA following CD19-directed
      CAR T-cell therapy for relapsed acute lymphoblastic leukemia.

PMID- 28766895
TI  - Pancreatic fat content assessed by 1 H magnetic resonance spectroscopy is
      correlated with insulin resistance, but not with insulin secretion, in Japanese
      individuals with normal glucose tolerance.
AB  - AIMS/INTRODUCTION: Whereas some clinical studies have shown that excessive fat
      accumulation in the pancreas is associated with impairment of insulin secretion,
      others have not found such an association. 1 H magnetic resonance spectroscopy
      allows quantitative fat analysis in various tissues including the pancreas. The
      pathological relevance of pancreatic fat content (PFC) in Japanese individuals
      remains unclear, however. MATERIALS AND METHODS: We analyzed PFC in 30 Japanese
      individuals with normal glucose tolerance by 1 H magnetic resonance spectroscopy,
      and then investigated the relationships between PFC and indexes of insulin
      secretion and insulin sensitivity-resistance determined by an oral glucose
      tolerance test. We also measured hepatic fat content and intramyocellular lipid
      content by 1 H magnetic resonance spectroscopy, as well as visceral fat area and
      subcutaneous fat area by magnetic resonance imaging, and we examined the
      relationships between these fat content measures and oral glucose tolerance test
      derived parameters. RESULTS: PFC was correlated with indexes of insulin
      sensitivity-resistance, but not with those of insulin secretion. Hepatic fat
      content and visceral fat area were correlated with similar sets of parameters as
      was PFC, whereas subcutaneous fat area was correlated with parameters of insulin
      secretion, and intramyocellular lipid content was not correlated with any of the
      measured parameters. The correlation between PFC and homeostasis model assessment
      of insulin resistance remained significant after adjustment for age, body mass
      index and sex. Among fat content measures, PFC was most highly correlated with
      hepatic fat content and visceral fat area. CONCLUSIONS: PFC was correlated with
      indexes of insulin resistance, but not with those of insulin secretion in non
      obese Japanese individuals with normal glucose tolerance.

PMID- 28766896
TI  - Novel Cranial Implants of Yttria-Stabilized Zirconia as Acoustic Windows for
      Ultrasonic Brain Therapy.
AB  - Therapeutic ultrasound can induce changes in tissues by means of thermal and
      nonthermal effects. It is proposed for treatment of some brain pathologies such
      as Alzheimer's, Parkinson's, Huntington's diseases, and cancer. However, cranium
      highly absorbs ultrasound reducing transmission efficiency. There are clinical
      applications of transcranial focused ultrasound and implantable ultrasound
      transducers proposed to address this problem. In this paper, biocompatible
      materials are proposed for replacing part of the cranium (cranial implants) based
      on low porosity polycrystalline 8 mol% yttria-stabilized-zirconia (8YSZ) ceramics
      as acoustic windows for brain therapy. In order to assess the viability of 8YSZ
      implants to effectively transmit ultrasound, various 8YSZ ceramics with different
      porosity are tested; their acoustic properties are measured; and the results are
      validated using finite element models simulating wave propagation to brain tissue
      through 8YSZ windows. The ultrasound attenuation is found to be linearly
      dependent on ceramics' porosity. Results for the nearly pore-free case indicate
      that 8YSZ is highly effective in transmitting ultrasound, with overall maximum
      transmission efficiency of ~81%, compared to near total absorption of cranial
      bone. These results suggest that 8YSZ polycrystals could be suitable acoustic
      windows for ultrasound brain therapy at 1 MHz.

PMID- 28766897
TI  - Removal of Organic Pollutants from Water Using Superwetting Materials.
AB  - The frequent occurrence of water pollution accidents and the leakage of organic
      pollutants have caused severe environmental and ecological crisis. It is thus
      highly imperative to find efficient materials to solve the problem. Inspired by
      the lotus leaf, superwetting materials are receiving increasing attention in the
      field of removal of organic pollutants from water. Various superwetting materials
      have been successfully generated and integrated into devices for removal of
      organic pollutants from water. On the basis of our previous work in the field, we
      summarized in this account the progress of removal of (1) floating and underwater
      insoluble, (2) emulsified insoluble, and (3) both insoluble and soluble organic
      pollutants from water using superwetting materials including superhydrophobic &
      superoleophilic materials, superhydrophilic & underwater superoleophobic
      materials, and materials with controllable wettability. The superwetting
      materials are in the forms of 2D porous materials, 3D porous materials and
      particles, etc. Finally, the current state and future challenges in this field
      are discussed. We hope this account could shed light on the design of novel
      superwetting materials for efficient removal of organic pollutants from water.

PMID- 28766900
TI  - Exploring the link between high grade internal rectal prolapse and faecal
      incontinence.

PMID- 28766903
TI  - Multimodal analysis of in vivo resorbable CaP bone substitutes by combining
      histology, SEM, and microcomputed tomography data.
AB  - This study introduced and demonstrated a new method to investigate the repair
      process of bone defects using micro- and macroporous beta-tricalcium phosphate
      (beta-TCP) substitutes. Specifically, the new method combined and aligned
      histology, SEM, and preimplantation microcomputed tomography (mCT) data to
      accurately characterize tissue phases found in biopsies, and thus better
      understand the bone repair process. The results included (a) the exact fraction
      of ceramic remnants (CR); (b) the fraction of ceramic resorbed and substituted by
      bone (CSB); and (c) the fraction of ceramic resorbed and not substituted by bone
      (CNSB). The new method allowed in particular the detection and quantification of
      mineralized tissues within the 1-10 um micropores of the ceramic ("micro-bone").
      The utility of the new method was demonstrated by applying it on biopsies of two
      beta-tricalcium phosphate bone substitute groups with two differing macropore
      sizes implanted in an ovine model for 6 weeks. The total bone deposition and
      ceramic resorption of the two substitute groups, having macropore sizes of 510
      and 1220 MUm, were 25.1 +/- 8.1% and 67.5 +/- 3.2%, and 24.4 +/- 4.1% and 61.4 +/
      6.5% for the group having the larger pore size. (c) 2017 Wiley Periodicals, Inc.
      J Biomed Mater Res Part B: Appl Biomater, 106B: 1567-1577, 2018.

PMID- 28766904
TI  - Technical note: TROG 15.01 SPARK trial multi-institutional imaging dose
      measurement.
AB  - PURPOSE: The Trans-Tasman Radiation Oncology Group (TROG) 15.01 Stereotactic
      Prostate Adaptive Radiotherapy utilizing Kilovoltage intrafraction monitoring
      (SPARK) trial is a multicenter trial using Kilovoltage Intrafraction Monitoring
      (KIM) to monitor prostate position during the delivery of prostate radiation
      therapy. KIM increases the accuracy of prostate radiation therapy treatments and
      allows for hypofractionation. However, an additional imaging dose is delivered to
      the patient. A standardized procedure to determine the imaging dose per frame
      delivered using KIM was developed and applied at four radiation therapy centers
      on three different types of linear accelerator. METHODS: Dose per frame for
      kilovoltage imaging in fluoroscopy mode was measured in air at isocenter using an
      ion chamber. Beam quality and dose were determined for a Varian Clinac iX linear
      accelerator, a Varian Trilogy, four Varian Truebeams and one Elekta Synergy at
      four different radiation therapy centers. The imaging parameters used on the
      Varian machines were 125 kV, 80 mA, and 13 ms. The Elekta machine was measured at
      120 kV, 80 mA, and 12 ms. Absorbed doses to the skin and the prostate for a
      typical SBRT prostate treatment length were estimated according to the IPEMB
      protocol. RESULTS: The average dose per kV frame to the skin was 0.24 +/- 0.03
      mGy. The average estimated absorbed dose to the prostate for all five treatment
      fractions across all machines measured was 39.9 +/- 2.6 mGy for 1 Hz imaging,
      199.7 +/- 13.2 mGy for 5 Hz imaging and 439.3 +/- 29.0 mGy for 11 Hz imaging.
      CONCLUSIONS: All machines measured agreed to within 20%. Additional dose to the
      prostate from using KIM is at most 1.3% of the prescribed dose of 36.25 Gy in
      five fractions delivered during the trial.

PMID- 28766905
TI  - Evidence for reduced neurogenesis in the aging human hippocampus despite stable
      stem cell markers.
AB  - Reduced neurogenesis in the aging mammalian hippocampus has been linked to
      cognitive deficits and increased risk of dementia. We utilized postmortem human
      hippocampal tissue from 26 subjects aged 18-88 years to investigate changes in
      expression of six genes representing different stages of neurogenesis across the
      healthy adult lifespan. Progressive and significant decreases in mRNA levels of
      the proliferation marker Ki67 (MKI67) and the immature neuronal marker
      doublecortin (DCX) were found in the healthy human hippocampus over the lifespan.
      In contrast, expression of genes for the stem cell marker glial fibrillary acidic
      protein delta and the neuronal progenitor marker eomesodermin was unchanged with
      age. These data are consistent with a persistence of the hippocampal stem cell
      population with age. Age-associated expression of the proliferation and immature
      neuron markers MKI67 and DCX, respectively, was unrelated, suggesting that
      neurogenesis-associated processes are independently altered at these points in
      the development from stem cell to neuron. These data are the first to demonstrate
      normal age-related decreases at specific stages of adult human hippocampal
      neurogenesis.

PMID- 28766906
TI  - CD66c (KOR-SA3544) antigen expression of leukemic blasts in pediatric acute
      myeloid leukemia with TLS/FUS-ERG fusion transcript.

PMID- 28766907
TI  - Neural correlates of "Theory of Mind" in very preterm born children.
AB  - Very preterm (VPT) birth (<32 weeks' gestational age) has been implicated in
      social-cognitive deficits including Theory of Mind (ToM); the ability to
      attribute mental states to others and understand that those beliefs can differ
      from one's own or reality. The neural bases for ToM deficits in VPT born children
      have not been examined. We used magnetoencephalography (MEG) for its excellent
      spatial and temporal resolution to determine the neural underpinnings of ToM in
      24 VPT and 24 full-term born (FT) children (7-13 years). VPT children performed
      more poorly on neuropsychological measures of ToM but not inhibition. In the MEG
      task, both FT children and VPT children recruited regions involved in false
      belief processing such as the rIFG (VPT: 275-350 ms, FT: 250-375 ms) and left
      inferior temporal gyrus (VPT: 375-450 ms, FT: 325-375 ms) and right fusiform
      gyrus (VPT: 150-200 ms, FT: 175-250 ms). The rIPL (included in the temporal
      parietal junction) was recruited in FT children (475-575 ms) and the lTPJ in VPT
      children (500-575 ms). However, activations in all regions were reduced in the
      VPT compared to the FT group. We suggest that with increasing social-cognitive
      demands such as varying the type of scenarios in the standardized measure of ToM,
      reduced activations in the rIFG and TPJ in the VPT group may reflect the
      decreased performance. With access to both spatial and temporal information, we
      discuss the role of domain general and specific regions of the ToM network in
      both groups. Hum Brain Mapp 38:5577-5589, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28766908
TI  - Building essential biodiversity variables (EBVs) of species distribution and
      abundance at a global scale.
AB  - Much biodiversity data is collected worldwide, but it remains challenging to
      assemble the scattered knowledge for assessing biodiversity status and trends.
      The concept of Essential Biodiversity Variables (EBVs) was introduced to
      structure biodiversity monitoring globally, and to harmonize and standardize
      biodiversity data from disparate sources to capture a minimum set of critical
      variables required to study, report and manage biodiversity change. Here, we
      assess the challenges of a 'Big Data' approach to building global EBV data
      products across taxa and spatiotemporal scales, focusing on species distribution
      and abundance. The majority of currently available data on species distributions
      derives from incidentally reported observations or from surveys where presence
      only or presence-absence data are sampled repeatedly with standardized protocols.
      Most abundance data come from opportunistic population counts or from population
      time series using standardized protocols (e.g. repeated surveys of the same
      population from single or multiple sites). Enormous complexity exists in
      integrating these heterogeneous, multi-source data sets across space, time, taxa
      and different sampling methods. Integration of such data into global EBV data
      products requires correcting biases introduced by imperfect detection and varying
      sampling effort, dealing with different spatial resolution and extents,
      harmonizing measurement units from different data sources or sampling methods,
      applying statistical tools and models for spatial inter- or extrapolation, and
      quantifying sources of uncertainty and errors in data and models. To support the
      development of EBVs by the Group on Earth Observations Biodiversity Observation
      Network (GEO BON), we identify 11 key workflow steps that will operationalize the
      process of building EBV data products within and across research infrastructures
      worldwide. These workflow steps take multiple sequential activities into account,
      including identification and aggregation of various raw data sources, data
      quality control, taxonomic name matching and statistical modelling of integrated
      data. We illustrate these steps with concrete examples from existing citizen
      science and professional monitoring projects, including eBird, the Tropical
      Ecology Assessment and Monitoring network, the Living Planet Index and the Baltic
      Sea zooplankton monitoring. The identified workflow steps are applicable to both
      terrestrial and aquatic systems and a broad range of spatial, temporal and
      taxonomic scales. They depend on clear, findable and accessible metadata, and we
      provide an overview of current data and metadata standards. Several challenges
      remain to be solved for building global EBV data products: (i) developing tools
      and models for combining heterogeneous, multi-source data sets and filling data
      gaps in geographic, temporal and taxonomic coverage, (ii) integrating emerging
      methods and technologies for data collection such as citizen science, sensor
      networks, DNA-based techniques and satellite remote sensing, (iii) solving major
      technical issues related to data product structure, data storage, execution of
      workflows and the production process/cycle as well as approaching technical
      interoperability among research infrastructures, (iv) allowing semantic
      interoperability by developing and adopting standards and tools for capturing
      consistent data and metadata, and (v) ensuring legal interoperability by
      endorsing open data or data that are free from restrictions on use, modification
      and sharing. Addressing these challenges is critical for biodiversity research
      and for assessing progress towards conservation policy targets and sustainable
      development goals.

PMID- 28766909
TI  - First reported case of magnesium-made bioresorbable scaffold to treat spontaneous
      left anterior descending coronary artery dissection.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare cause of Acute Coronary
      Syndrome. Although its treatment is still debated, use of Bioreasorbable Scaffold
      was recently advocated as an attractive option in this setting. We report the
      first case, to our knowledge, of a new magnesium-made Bioresorbable Scaffold
      implantation in a young woman presenting with Non-ST- Elevation Myocardial
      Infarction and a rapid worsening SCAD.

PMID- 28766910
TI  - Lack of TMEM230 mutations in patients with familial and sporadic Parkinson's
      disease in a Taiwanese population.
AB  - Mutations in transmembrane protein 230 (TMEM230) have recently been reported to
      be associated with Parkinson's disease (PD) in a North American population. A
      highly prevalent mutation, c.550_552delTAGinsCCCGGG (p.*184ProGlyext*5) was found
      in 3.1% of Chinese familial PD patients. However, subsequent studies failed to
      replicate these findings in different populations. Our objective was to confirm
      the role of this gene in a large number of PD patients and controls in a
      Taiwanese population. Among 1,672 participants, we sequenced all coding exons and
      exon-intron boundary junctions of the TMEM230 gene in 180 probands with familial
      PD. We also genotyped the potential pathogenic variants identified and the
      previously reported mutations (p.Arg141Leu, p.Tyr92Cys, p.*184Trpext*5, and
      p.*184ProGlyext*5) in an additional cohort of 500 patients with sporadic PD, and
      992 age and gender-matched neurologically normal control subjects. We did not
      find any of the previously reported mutations, but we observed one novel missense
      exonic variant, c.G68A (p.Arg23Gln), in one patient with familial PD, and two
      patients with sporadic PD in a heterozygous state. However, subsequent analysis
      of this variant in 992 controls did not find any significant associations between
      p.Arg23Gln and the risk of PD (0.44% vs. 0.30%, p = 0.22). Our findings suggest
      that genetic variants of TMEM230 do not play a major role in PD in our Taiwanese
      population. Further experimental studies are warranted to confirm the
      pathogenicity of this gene in PD disease process.

PMID- 28766911
TI  - From Fenestrindane towards Saddle-Shaped Nanographenes Bearing a Tetracoordinate
      Carbon Atom.
AB  - Two saddle-shaped polycyclic aromatic compounds (8 a and 8 b) bearing an all-cis
      [5.5.5.5]fenestrane core surrounded by an o,p,o,p,o,p,o,p-cyclooctaphenylene belt
      were synthesized and characterized by NMR spectroscopy and mass spectrometry. The
      key step of this synthesis involves the formation of four cycloheptatriene rings
      from the corresponding electron-rich 1,4,9,12-tetraarylfenestrindane derivatives
      7 a and 7 b in Scholl-type cyclizations. The structural details of the D2d 
      symmetric saddle compound 8 a were determined by X-ray crystallography, and the
      properties of 8 a and 8 b were studied by UV/Vis and fluorescence spectroscopy
      and cyclic voltammetry.

PMID- 28766912
TI  - Measurement of the zygomatic region for the optimal placement of quad zygomatic
      implants.
AB  - BACKGROUND: The zygomatic implant is suggested to be placed in zygomatic areas
      with the largest thickness, but regions to obtain the largest bone-to-implant
      contact (BIC) were unknown. PURPOSE: To identify the zygomatic regions for
      placing quad zygomatic implants that obtain the largest BIC. MATERIALS AND
      METHODS: The zygomatic thicknesses of 300 zygomata were measured at total 12
      points on the superior, middle, and inferior areas on the 3-dimensional
      reconstruction images. In 50 edentulous maxillae, the zygomatic BICs of virtually
      placed implants were measured and the incidence of the intrusion into the
      infratemporal fossa calculated at each point. RESULTS: The largest thickness in
      the superior, middle, and inferior regions were at Point A1 (8.01 +/- 2.10 mm),
      Point B1 (7.02 +/- 1.73 mm), and Point C0 (6.65 +/- 1.66 mm), respectively. The
      virtually placed implants at Point A3 (16.70 +/- 4.18 mm) and Point B1 (12.07 +/-
      3.84 mm) had the highest BICs while retaining the minimum incidence of the
      intrusion complications. CONCLUSION: To obtain the largest BICs and avoid the
      intrusion complications, results suggested that the postero-superior region
      (Point A3 ) and the center of zygoma (Point B1 ) were the optimal places for the
      placement of quad zygomatic implants.

PMID- 28766913
TI  - Feasibility and acceptability of a text message intervention used as an adjunct
      tool by WIC breastfeeding peer counsellors: The LATCH pilot.
AB  - Breastfeeding rates among mothers in the Supplemental Nutrition Program for
      Women, Infants, and Children (WIC) are lower than for other mothers in the United
      States. The objective of this study was to test the acceptability and feasibility
      of the Lactation Advice thru Texting Can Help intervention. Mothers were enrolled
      at 18-30 weeks gestation from two WIC breastfeeding peer counselling (PC)
      programmes if they intended to breastfeed and had unlimited text messaging, more
      than fifth-grade literacy level, and fluency in English or Spanish. Participants
      were randomized to the control arm (PC support without texting) or the
      intervention arm (PC support with texting). The two-way texting intervention
      provided breastfeeding education and support from peer counsellors. Primary
      outcomes included early post-partum (PP) contact and exclusive breastfeeding
      (EBF) rates at 2 weeks PP. Feasibility outcomes included text messaging
      engagement and mother's satisfaction with texting platform. Fifty-eight women
      were enrolled, 52 of whom were available for intention-to-treat analysis (n = 30
      texting, n = 22 control). Contact between mothers and PCs within 48 hr of
      delivery was greater in the texting group (86.6% vs. 27.3%, p < .001). EBF rates
      at 2 weeks PP among participants in the texting intervention was 50% versus 31.8%
      in the control arm (p = .197). Intervention group mothers tended to be more
      likely to meet their breastfeeding goals (p = .06). Participants were highly
      satisfied with the Lactation Advice thru Texting Can Help intervention, and
      findings suggest that it may improve early post-delivery contact and increase EBF
      rates among mothers enrolled in WIC who receive PC. A large, multicentre trial is
      feasible and warranted.

PMID- 28766914
TI  - Skeletal muscle dispersion (400-1000 nm) and kinetics at optical clearing.
AB  - Skeletal muscle dispersion and optical clearing (OC) kinetics were studied
      experimentally to prove the existence of the refractive index (RI) matching
      mechanism of OC. Sample thickness and collimated transmittance spectra were
      measured during treatments with glucose (40%) and ethylene glycol (EG; 99%)
      solutions and used to obtain the time dependence of the RI of tissue fluids based
      on the proposed theoretical model. Calculated results demonstrated an increase of
      RI of tissue fluids and consequently proved the occurrence of the RI matching
      mechanism. The RI increase was observed for the wavelength range between 400 and
      1000 nm and for the 2 probing molecules explored. We found that for 30 min
      treatment with 40% glucose and 99% EG, RI of sarcoplasm plus interstitial fluid
      was increased at 800 nm from 1.328 to 1.348 and from 1.328 to 1.369,
      respectively.

PMID- 28766915
TI  - Metabolomics analysis reveals distinct profiles of nonmuscle-invasive and muscle
      invasive bladder cancer.
AB  - Urothelial carcinoma is the most common form of bladder cancer, but pathway
      changes that occur with stage-wise progression have not been well defined. We
      used a metabolomics approach to identify potential metabolic pathways uniquely
      altered in normal urothelium, nonmuscle-invasive bladder cancer (NMIBC), and
      muscle-invasive bladder cancer (MIBC). We performed global metabolomic profiling
      using GC-mass spectrometry (MS) and LC-MS platforms to identify metabolite
      signatures between normal urothelium and high-grade urothelial carcinoma of
      different stages. Pathways globally dysregulated in cancer relative to normal
      urothelium included glucose, tricarboxylic acid (TCA) cycle, lipid, amino acid,
      and nucleotide pathways. Urothelial carcinoma showed elevated glucose utilization
      for glycolysis and increased sorbitol pathway intermediates, consistent with
      Warburg effect. Anaplerosis to sustain energy production suggested by increased
      late TCA cycle intermediates, amino acids, and dipeptides occurs in bladder
      cancer. Urothelial carcinoma also shows altered membrane lipid membrane
      metabolism and differential derivation of nucleic acid components pyrimidine and
      purine. In stage comparison, MIBC appears to preferentially enhance
      cyclooxygenase (COX) and lipoxygenase (LOX) signaling, increase heme catabolism,
      and alter nicotinamide adenine dinucleotide (NAD+) synthesis with a possible
      influence from associated inflammatory cells. We identify numerous metabolomic
      alterations in NMIBC and MIBC that likely reflect underlying pathway changes.
      Differential pathway activity may have value in designing stage-specific novel
      therapeutics in urothelial carcinoma.

PMID- 28766916
TI  - Interleukin-18 (IL-18) is equally expressed in inflammatory breast cancer and
      noninflammatory locally advanced breast cancer: A possible association with
      chemotherapy response.
AB  - AIM: Inflammatory breast cancer (IBC) is the most aggressive form of locally
      advanced breast cancer. The signs of inflammation such as hyperemia and
      hyperthermia might suggest the possible participation of inflammatory mediators.
      This study investigates stromal and tumor expression of nuclear factor-kappa B
      (NF-kappaB) and interleukin-18 (IL-18) in samples obtained from IBC and
      noninflammatory locally advanced breast cancer (LABC) and the influence of these
      markers on patients' prognosis. METHODS: Demographic data, tumor molecular
      characteristics and overall survival in both groups were also assessed.
      Furthermore, in this study, we evaluated the expression of IL-18 and p50 nuclear
      fraction of NF-kappaB by immunohistochemistry in specimens from IBC and LABC
      (T4b). RESULTS: We observed that 24.6% of women were diagnosed with IBC up to age
      40. In addition, the patients with IBC showed a lower overall survival when
      compared to LABC. In regard to molecular markers, ER+ , C-erbB2- or triple
      negative IBC patients showed a significantly reduced overall survival. In
      addition, a higher IL-18 immunostaining in stroma of IBC and LABC was observed in
      comparison with tumor cells, but stromal immunoexpression was similar between IBC
      and LABC. Besides, IL-18 positivity seemed be related with a better clinical
      response to neoadjuvant chemotherapy. However, NF-kappaB expression was identical
      in both groups. CONCLUSION: The IL-18 is present in tumor stroma of IBC and LABC
      and seems to be associated with the complete response to neoadjuvant
      chemotherapy.

PMID- 28766917
TI  - Accelerated oligosaccharide absorption and altered serum metabolites during oral
      glucose tolerance test in young Japanese with impaired glucose tolerance.
AB  - AIMS/INTRODUCTION: Impaired glucose tolerance (IGT) is a subtype of prediabetes,
      a condition having high risk for development to diabetes mellitus, but its
      pathophysiology is not fully understood. In the present study, we examined
      metabolic changes in IGT by using two types (D-glucose [Glc] and partial
      hydrolysate of starch [PHS]) of oral glucose tolerance tests (OGTTs), with
      emphasis on serum incretins and metabolites. MATERIALS AND METHODS: We carried
      out the two types of OGTT (Glc/OGTT and PHS/OGTT) in 99 young Japanese
      individuals who had tested either positive (GU+ ; n = 48) or negative (GU- ; n =
      51) for glycosuria. After OGTT, they were sub-grouped into five categories:
      normal glucose tolerance (NGT) in the GU- group (GU- /NGT; n = 49), NGT in the
      GU+ group (GU+ /NGT; n = 28), IGT (n = 12), diabetes mellitus (n = 1) and renal
      glycosuria (n = 9). Serum incretin and metabolites of GU- /NGT and IGT were then
      measured. RESULTS: When the serum insulin level at each time-point during
      PHS/OGTT was expressed as its ratio relative to Glc/OGTT, it was increased time
      dependently in GU- /NGT, but not in IGT. Such an increase in the ratio was also
      detected of serum incretin levels in GU- /NGT, but not in IGT, suggesting a lack
      of deceleration of oligosaccharide absorption in IGT. Metabolome analysis showed
      a difference in the serum levels of two metabolites of unknown function in
      mammals, methylcysteine and sedoheptulose 1,7-bisphosphate, between GU- /NGT and
      IGT. CONCLUSIONS: Comparison of PHS/OGTT and Glc/OGTT showed that oligosaccharide
      absorption was accelerated in IGT. Methylcysteine and sedoheptulose 1,7
      bisphosphate could be novel markers for dysregulated glucose metabolism.

PMID- 28766918
TI  - The skin microbiome and immune system: Potential target for chemoprevention?
AB  - There has been increasing interest in understanding the role of the human
      microbiome in skin diseases. Microbiome studies are being utilized in skin cancer
      research in numerous ways. Commensal bacteria are being studied as a potential
      tool to judge the biggest environmental risk of skin cancer, ultraviolet (UV)
      radiation. Owing to the recognized link of skin microbes in the process of
      inflammation, there have been theories linking commensal bacteria to skin cancer.
      Viral metagenomics has also provided insight into virus linked forms of skin
      cancers. Speculations can be drawn for skin microbiome that in a manner similar
      to gut microbiome, they can be involved in chemoprevention of skin cancer.
      Nonetheless, there are definitely huge gaps in our knowledge of the relationship
      of microbiome and skin cancers, especially in relation to chemoprevention. The
      utilization of microbiome in skin cancer research seems to be a promising field
      and may help yield novel skin cancer prevention and treatment options. This
      review focuses on recent utilization of the microbiome in skin cancer research,
      and it explores the potential of utilizing the microbiome in prevention, earlier
      diagnosis, and treatment of skin cancers.

PMID- 28766919
TI  - Turbulent kinetic energy in the right ventricle: Potential MR marker for risk
      stratification of adults with repaired Tetralogy of Fallot.
AB  - PURPOSE: To assess right ventricular (RV) turbulent kinetic energy (TKE) in
      patients with repaired Tetralogy of Fallot (rToF) and a spectrum of pulmonary
      regurgitation (PR), as well as to investigate the relationship between these 4D
      flow markers and RV remodeling. MATERIALS AND METHODS: Seventeen patients with
      rToF and 10 healthy controls were included in the study. Patients were divided
      into two groups based on PR fraction: one lower PR fraction group (<=11%) and one
      higher PR fraction group (>11%). Field strength/sequences: 3D cine phase contrast
      (4D flow), 2D cine phase contrast (2D flow), and balanced steady-state free
      precession (bSSFP) at 1.5T. ASSESSMENT: The RV volume was segmented in the
      morphologic short-axis images and TKE parameters were computed inside the
      segmented RV volume throughout diastole. Statistical tests: One-way analysis of
      variance with Bonferroni post-hoc test; unpaired t-test; Pearson correlation
      coefficients; simple and stepwise multiple regression models; intraclass
      correlation coefficient (ICC). RESULTS: The higher PR fraction group had more
      remodeled RVs (140 +/- 25 vs. 107 +/- 22 [lower PR fraction, P < 0.01] and 93 +/-
      15 ml/m2 [healthy, P < 0.001] for RV end-diastolic volume index [RVEDVI]) and
      higher TKE values (5.95 +/- 3.15 vs. 2.23 +/- 0.81 [lower PR fraction, P < 0.01]
      and 1.91 +/- 0.78 mJ [healthy, P < 0.001] for Peak Total RV TKE). Multiple
      regression analysis between RVEDVI and 4D/2D flow parameters showed that Peak
      Total RV TKE was the strongest predictor of RVEDVI (R2  = 0.47, P = 0.002).
      CONCLUSION: The 4D flow-specific TKE markers showed a slightly stronger
      association with RV remodeling than conventional 2D flow PR parameters. These
      results suggest novel hemodynamic aspects of PR in the development of late
      complications after ToF repair. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2
      J. Magn. Reson. Imaging 2018;47:1043-1053.

PMID- 28766920
TI  - Temozolomide alone or in combination with doxorubicin as a rescue agent in 37
      cases of canine multicentric lymphoma.
AB  - Temozolomide (TMZ) is an alkylating agent previously used in conjunction with
      doxorubicin (DOX) to treat dogs with relapsed lymphoma. However, there are very
      limited data for this drug when used as single agent. The aim of this
      retrospective study was to evaluate the efficacy and toxicity of TMZ in dogs with
      relapsed multicentric lymphoma that failed multi-agent chemotherapy protocols,
      and compare the outcome to a group of dogs receiving the same drug in combination
      with DOX. Twenty-six patients were included in the TMZ group and 11 in the
      TMZ/DOX group. Responses were evaluated via retrospective review of the medical
      records. The overall median survival time (MST) for both groups was 40 days
      (range 1-527 days). For the TMZ group, median time to progression (TTP) was 15
      days (range 1-202 days) and MST 40 days (range 1-527 days), with an overall
      response rate (ORR) of 32% and 46% recorded toxicities. For the TMZ/DOX group,
      median TTP was 19 days (range 2-87 days) and MST 24 days (range 3-91 days), with
      an ORR of 60% and 63% recorded toxicities. However, a proportion of
      haematological toxicoses may have gone undetected due to the absence of
      associated clinical signs. The difference in MST and TTP between the 2 groups was
      not statistically significant. Similarly, no negative prognostic factors were
      identified. Although responses were generally short lived, this study suggests
      that TMZ may achieve similar efficacy to TMZ/DOX whilst being associated with a
      lower frequency of recorded toxicities.

PMID- 28766921
TI  - The dopamine transporter role in psychiatric phenotypes.
AB  - The dopamine transporter (DAT) is one of the most relevant and investigated
      neurotransmitter transporters. DAT is a plasma membrane protein which plays a
      homeostatic role, controlling both extracellular and intracellular concentrations
      of dopamine (DA). Since unbalanced DA levels are known to be involved in numerous
      mental disorders, a wealth of investigations has provided valuable insights
      concerning DAT role into normal brain functioning and pathological processes.
      Briefly, this extensive but non-systematic review discusses what is recently
      known about the role of SLC6A3 gene which encodes the dopamine transporter in
      psychiatric phenotypes. DAT protein, SLC6A3 gene, animal models, neuropsychology,
      and neuroimaging investigations are also concisely discussed. To conclude,
      current challenges are reviewed in order to provide perspectives for future
      studies.

PMID- 28766922
TI  - Maternal prepregnancy obesity and the risk of shoulder dystocia: a meta-analysis.
AB  - BACKGROUND: Results from epidemiological studies about the association between
      maternal prepregnancy obesity and the risk of shoulder dystocia are inconsistent.
      OBJECTIVE: To evaluate the effect of maternal prepregnancy obesity on the risk of
      shoulder dystocia. SEARCH STRATEGY: We searched PubMed and the Web of Science
      database for all relevant studies up to 5 August 2016 and reviewed the reference
      lists of identified articles. SELECTION CRITERIA: Observational studies that
      investigated the association between prepregnancy obesity and the risk of
      shoulder dystocia were included. DATA COLLECTION AND ANALYSIS: A total of 20
      articles involving 2 153 898 participants were included in this meta-analysis. A
      random-effects model was used to calculate the pooled relative risks (RRs) with
      95% CIs. MAIN RESULTS: For obese versus nonobese, the pooled RR of shoulder
      dystocia was 1.63 (95% CI: 1.33-1.99). The findings remained significant in the
      cohort studies (RR = 1.57, 95% CI: 1.28-1.93) and case-control studies (RR =
      2.70, 95% CI: 1.46-4.98). With regard to the subgroup 'continents', there was a
      significant association between obesity and the risk of shoulder dystocia in
      Europe (RR = 1.51, 95% CI: 1.18-1.92) and Asia (RR = 2.59, 95% CI: 1.15-5.83).
      The result from the sensitivity analysis for studies adjusted for gestational
      diabetes was significant (RR = 1.61, 95% CI: 1.05-2.47). The pooled RRs for
      obesity classes I, II and III versus nonobese were 1.29 (95% CI: 1.06-1.57), 1.94
      (95% CI: 1.26-2.98) and 2.47 (95% CI: 1.56-3.93), respectively. CONCLUSION: This
      meta-analysis suggests that maternal prepregnancy obesity is associated with an
      increased risk of shoulder dystocia. TWEETABLE ABSTRACT: A meta-analysis shows
      that maternal prepregnancy obesity increases the risk of shoulder dystocia.

PMID- 28766923
TI  - Comparison of higher-order multiphoton signal generation and collection at the
      1700-nm window based on transmittance measurement of objective lenses.
AB  - One benefit of excitation at the 1700-nm window is the more accessible modalities
      of multiphoton signal generation. It is demonstrated here that the transmittance
      performance of the objective lens is of vital importance for efficient higher
      order multiphoton signal generation and collection excited at the 1700-nm window.
      Two commonly used objective lenses for multiphoton microscopy (MPM) are
      characterized and compared, one with regular coating and the other with
      customized coating for high transmittance at the 1700-nm window. Our results show
      that, fourth harmonic generation imaging of mouse tail tendon and 5-photon
      fluorescence of carbon quantum dots using the regular objective lens shows an
      order of magnitude signal higher than those using the customized objective lens.
      Besides, the regular objective lens also enables a 3-photon fluorescence imaging
      depth of >1600 MUm in mouse brain in vivo. Our results will provide guidelines
      for objective lens selection for MPM at the 1700-nm window.

PMID- 28766924
TI  - Factors associated with performing urgent coronary angiography in out-of-hospital
      cardiac arrest patients.
AB  - OBJECTIVES: Factors associated with performing urgent coronary angiography (UCA)
      in patients with out-of-hospital cardiac arrest (OHCA) were identified.
      BACKGROUND: Current guidelines for resuscitated OHCA patients recommend UCA if
      there is ST-elevation on post-arrest electrocardiogram or high suspicion of acute
      myocardial infarction. Some have advocated for UCA in all OHCA regardless of
      suspected etiology. The reasons for variations in performing UCA are not well
      understood. METHODS: A retrospective analysis of subjects presenting with
      resuscitated OHCA to a single academic medical center from 12/15/2007 to
      8/31/2014 was conducted. Demographic and clinical characteristics of patients
      undergoing UCA, defined as angiography within 6 hr of presentation, were compared
      with those not undergoing UCA. Logistic regression was used to determine
      predictors of UCA. RESULTS: A total of 323 resuscitated OHCA patients (mean age,
      64 years; women, 35%) were included in the analysis; 107 (33.1%) underwent
      coronary angiography during their hospitalization and 66 (20.4%) underwent UCA.
      Multivariable adjusted factors associated with UCA were ST-elevation [odds ratio
      (OR) 14.66, 95% confidence interval (CI) 6.28-34.24, P < 0.001], initial
      shockable rhythm (OR 3.69, 95% CI 1.52-8.97, P = 0.004), and history of coronary
      artery disease (CAD) (OR 3.37, 95% CI 1.43-7.95, P = 0.005). Higher age (OR 0.71
      per decade, 95% CI 0.55-0.92, P = 0.01) and obvious non-cardiac cause of arrest
      (OR 0.08, 95% CI 0.02-0.38, P = 0.001) were negatively associated with UCA.
      CONCLUSIONS: In resuscitated out-of-hospital cardiac arrest patients, ST
      elevation, shockable rhythm, and history of CAD were associated with performing
      urgent coronary angiography; older patients and those with obvious non-cardiac
      causes of arrest were negatively associated.

PMID- 28766926
TI  - Brownish-yellowish plaque on the penis shaft.

PMID- 28766925
TI  - Posterior column ataxia with retinitis pigmentosa coexisting with sensory
      autonomic neuropathy and leukemia due to the homozygous p.Pro221Ser FLVCR1
      mutation.
AB  - FLVCR1 encodes for a ubiquitous heme exporter, whose recessive mutations cause
      posterior column ataxia with retinitis pigmentosa (PCARP). Recently, FLVCR1
      recessive mutations were also found in two sporadic children with hereditary
      sensory-autonomic neuropathy (HSAN). We report the unique case of a 33-year-old
      Italian woman with a combination of typical PCARP, sensory-autonomic neuropathy
      with sensory loss to all modalities and multiple autonomic dysfuctions, and acute
      lymphocytic leukemia. Molecular analysis demonstrated homozygosity for the
      previously identified FLVCR1 p.Pro221Ser variation. The same variation, in
      combination with a frameshift mutation, was previously identified in an Italian
      child with HSAN. Functional studies carried out on patient-derived lymphoblastoid
      cell lines showed decreased FLVCR1a transcript, increased reactive oxygen
      species, excessive intracellular heme accumulation, and increased number of
      Annexin V positive cells. This indicates that the homozygous p.Pro221Ser FLVCR1
      variation compromises the ability of FLVCR1a to export heme leading to enhanced
      susceptibility to programmed cell death. Our study demonstrates the existence of
      a phenotypic continuum among the discrete disorders previously linked to FLVCR1
      mutations, and suggests that the related alteration of heme metabolism may lead
      to the degeneration of specific neuronal cell populations.

PMID- 28766927
TI  - Combining hyperspectral imaging and chemometrics to assess and interpret the
      effects of environmental stressors on zebrafish eye images at tissue level.
AB  - Changes on an organism by the exposure to environmental stressors may be
      characterized by hyperspectral images (HSI), which preserve the morphology of
      biological samples, and suitable chemometric tools. The approach proposed allows
      assessing and interpreting the effect of contaminant exposure on heterogeneous
      biological samples monitored by HSI at specific tissue levels. In this work, the
      model example used consists of the study of the effect of the exposure of
      chlorpyrifos-oxon on zebrafish tissues. To assess this effect, unmixing of the
      biological sample images followed by tissue-specific classification models based
      on the unmixed spectral signatures is proposed. Unmixing and classification are
      performed by multivariate curve resolution-alternating least squares (MCR-ALS)
      and partial least squares-discriminant analysis (PLS-DA), respectively. Crucial
      aspects of the approach are: (1) the simultaneous MCR-ALS analysis of all images
      from 1 population to take into account biological variability and provide
      reliable tissue spectral signatures, and (2) the use of resolved spectral
      signatures from control and exposed populations obtained from resampling of pixel
      subsets analyzed by MCR-ALS multiset analysis as information for the tissue
      specific PLS-DA classification models. Classification results diagnose the
      presence of a significant effect and identify the spectral regions at a tissue
      level responsible for the biological change.

PMID- 28766928
TI  - Unusual Passivation Ability of Superconcentrated Electrolytes toward Hard Carbon
      Negative Electrodes in Sodium-Ion Batteries.
AB  - The passivation of negative electrodes is key to achieving prolonged charge
      discharge cycling with Na-ion batteries. Here, we report the unusual passivation
      ability of superconcentrated Na-salt electrolytes. For example, a 50 mol % sodium
      bis(fluorosulfonyl)amide (NaFSA)/succinonitrile (SN) electrolyte enables highly
      reversible Na+ insertion into a hard carbon negative electrode without any
      electrolyte additive, functional binder, or electrode pretreatment. Importantly,
      an anion-derived passivation film is formed via preferential reduction of the
      anion upon charging, which can effectively suppress further electrolyte
      reduction. As a structural characteristic of the electrolyte, most anions are
      coordinated to multiple Na+ cations at high concentration, which shifts the
      lowest unoccupied molecular orbitals of the anions downward, resulting in
      preferential anion reduction. The present work provides a new understanding of
      the passivation mechanism with respect to the coordination state of the anion.

PMID- 28766929
TI  - Size- and Density-Controllable Fabrication of the Platinum Nanoparticle/ITO
      Electrode by Pulse Potential Electrodeposition for Ammonia Oxidation.
AB  - Pulse potential electrodeposition was successfully utilized to electrochemically
      fabricate platinum (Pt) nanoparticles on indium tin oxide (ITO) conductive glass
      substrates for catalysis toward ammonia electro-oxidation. The effect of
      deposition parameters (lower potential El, lower potential duration tl, and upper
      potential duration tu) on the size and number density of Pt nanoparticles was
      investigated by scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM). The electrocatalytic activity of the Pt nanoparticle/ITO
      electrode for ammonia oxidation was characterized by the cyclic voltammetry (CV)
      method. The results showed that lower El and longer tl accelerate the formation
      of Pt nuclei while longer tu favors the growth of grain size to some extent, as
      El mainly tunes electrochemical overpotential while tl and tu affect the
      activation and mass transfer process. By the tuning of the deposition parameters,
      Pt nanoparticle/ITO electrodes with a polycrystalline nature and 5 nm-scale
      primary particles, could be easily modified in Pt particle size and number
      density. Furthermore, the Pt nanoparticle/ITO electrode shows high mass specific
      catalytic activity (MA) toward ammonia oxidation (1.65 mC MUg-1), much higher
      than that of the commercial Pt/C electrode (0.32 mC MUg-1). Additionally, the
      high catalytic performance results not only from the nanosize effect of Pt
      nanoparticles, but also from the special morphology formed during the
      electrodeposition process.

PMID- 28766930
TI  - Unusual Mesoporous Carbonaceous Matrix Loading with Sulfur as the Cathode of
      Lithium Sulfur Battery with Exceptionally Stable High Rate Performance.
AB  - Unusual three-dimensional mesoporous carbon/reduced graphene oxide (MP-C/rGO)
      matrix possessing graphene nanolayer pore walls built up by three to five
      graphene monosheets and some carbon particles with the sizes of about 5 nm
      located between the graphene nanolayers was prepared by facile freeze-drying and
      then carbonization of the poly(vinyl alcohol) and graphene oxide mixture. The
      mesoporous carbonaceous MP-C/rGO sample has a high specific surface area of 661.6
      m2 g-1, large specific pore volume of 1.54 m3 g-1, and focused pore size
      distribution of 2-10 nm. About 64 wt % sulfur could be held in the pores of the
      MP-C/rGO matrix. As the cathode of a Li-S battery, the MP-C/rGO/S composite
      showed excellent electrochemical property including a high initial specific
      capacity of 919 mA h g-1 at 1 C with the capacity retention ratio of 63.3% and
      the Coulombic efficiency above 90% after 500 cycles. Meanwhile, the initial
      specific capacity of 602 mA h g-1 at 5 C and remaining capacity of 391 mA h g-1
      after 500 cycles with an outstanding Coulombic efficiency of 97% indicate its
      exceptionally stable rate performance.

PMID- 28766931
TI  - Thermally Stable Cellulose Nanocrystals toward High-Performance 2D and 3D
      Nanostructures.
AB  - Cellulose nanomaterials have attracted much attention in a broad range of fields
      such as flexible electronics, tissue engineering, and 3D printing for their
      excellent mechanical strength and intriguing optical properties. Economic,
      sustainable, and eco-friendly production of cellulose nanomaterials with high
      thermal stability, however, remains a tremendous challenge. Here versatile
      cellulose nanocrystals (DM-OA-CNCs) are prepared through fully recyclable oxalic
      acid (OA) hydrolysis along with disk-milling (DM) pretreatment of bleached kraft
      eucalyptus pulp. Compared with the commonly used cellulose nanocrystals from
      sulfuric acid hydrolysis, DM-OA-CNCs show several advantages including large
      aspect ratio, carboxylated surface, and excellent thermal stability along with
      high yield. We also successfully demonstrate the fabrication of high-performance
      films and 3D-printed patterns using DM-OA-CNCs. The high-performance films with
      high transparency, ultralow haze, and excellent thermal stability have the great
      potential for applications in flexible electronic devices. The 3D-printed
      patterns with porous structures can be potentially applied in the field of tissue
      engineering as scaffolds.

PMID- 28766932
TI  - Electronic Structure Calculations of Hydrogen Storage in Lithium-Decorated Metal
      Graphyne Framework.
AB  - Porous metal-graphyne framework (MGF) made up of graphyne linker decorated with
      lithium has been investigated for hydrogen storage. Applying density functional
      theory spin-polarized generalized gradient approximation with the Perdew-Burke
      Ernzerhof functional containing Grimme's diffusion parameter with double numeric
      polarization basis set, the structural stability, and physicochemical properties
      have been analyzed. Each linker binds two Li atoms over the surface of the
      graphyne linker forming MGF-Li8 by Dewar coordination. On saturation with
      hydrogen, each Li atom physisorbs three H2 molecules resulting in MGF-Li8-H24. H2
      and Li interact by charge polarization mechanism leading to elongation in average
      H-H bond length indicating physisorption. Sorption energy decreases gradually
      from ~0.4 to 0.20 eV on H2 loading. Molecular dynamics simulations and computed
      sorption energy range indicate the high reversibility of H2 in the MGF-Li8
      framework with the hydrogen storage capacity of 6.4 wt %. The calculated
      thermodynamic practical hydrogen storage at room temperature makes the Li
      decorated MGF system a promising hydrogen storage material.

PMID- 28766933
TI  - Dual-Functional Electrocatalyst Derived from Iron-Porphyrin-Encapsulated Metal
      Organic Frameworks.
AB  - Active, stable electrocatalysts based on non-precious metals for the oxygen
      reduction reaction (ORR) and hydrogen evolution reaction (HER) are critical for
      the development of cost-effective, efficient renewable energy technologies. Here,
      Fe/Fe3C-embedded nitrogen-doped carbon was fabricated via pyrolysis of iron
      porphyrin-encapsulated mesoporous metal-organic frameworks [PCN-333 (Fe), where
      "PCN" stands for "porous coordination network"] at 700  degrees C. The various
      characterization techniques confirmed that Fe- and Fe3C-containing Fe-N-C
      material (FeP-P333-700) was successfully prepared by pyrolysis of porphyrin
      encapsulated PCN-333 (Fe). FeP-P333-700 exhibited superior electrocatalytic
      performance for the ORR and HER owing to the synergistic effect of Fe/Fe3C and Fe
      N-C active sites.

PMID- 28766934
TI  - Iodine Atom or Hypoiodous Acid? Comment on "Rapid Selective Circumneutral
      Degradation of Phenolic Pollutants Using Peroxymonosulfate-Iodide Metal-Free
      Oxidation: Role of Iodine Atoms".

PMID- 28766935
TI  - Poly(ester amide)s from Poly(ethylene terephthalate) Waste for Enhancing Bone
      Regeneration and Controlled Release.
AB  - The present study elucidates the facile synthesis and exceptional properties of a
      family of novel poly(ester amide)s (PEAs) based on bis(2-hydroxy ethylene)
      terephthalamide that was obtained from the poly(ethylene terephthalate) waste.
      Fourier transform infrared and 1H NMR were used to verify the presence of ester
      and amide in the polymer backbone. Differential scanning calorimetry data showed
      that the glass transition temperature decreased with as the chain length of
      dicarboxylic acids increased. Dynamic mechanical analysis and contact angle
      studies proved that the modulus values and hydrophobicity increased with as the
      chain lengths of dicarboxylic acids increased. In vitro hydrolytic degradation
      and dye release studies demonstrated that the degradation and release decreased
      with as the chain lengths of dicarboxylic acids increased. Modeling these data
      illustrated that degradation and release follow first-order degradation and zero
      order release, respectively. The in vitro cytocompatibility studies confirmed the
      minimal toxicity characteristic of these polymers. Osteogenic studies proved that
      these polymers can be highly influential in diverting the cells toward osteogenic
      lineage. Alizarin red staining evinced the presence of twice the amount of
      calcium phosphate deposits by the cells on these polymers when compared to the
      control. The observed result was also corroborated by the increased expression of
      alkaline phosphatase. These findings were further validated by the markedly
      higher mRNA expressions for known osteogenic markers using real time polymerase
      chain reaction. Therefore, these polymers efficiently promoted osteogenesis. This
      study demonstrates that the physical properties, degradation, and release
      kinetics can be altered to meet the specific requirements in organ regeneration
      as well as facilitate simultaneous polymer resorption through control of the
      chain length of the monomers. The findings of this study have significant
      implications for designing cost-effective biodegradable polymers for tissue
      engineering.

PMID- 28766936
TI  - Polymeric Self-Assembled Monolayers Anomalously Improve Thermal Transport across
      Graphene/Polymer Interfaces.
AB  - Ultralow thermal conductivities of bulk polymers greatly limit their applications
      in areas demanding fast heat dissipation, such as flexible electronics and
      microelectronics. Therefore, polymeric composites incorporating highly thermally
      conductive filler materials (e.g., graphene and carbon nanotubes) have been
      produced to address the issue. However, despite some enhancement, thermal
      conductivities of these materials are still far below theoretical predictions,
      mainly due to the inefficient thermal transport across material interfaces. Here,
      using molecular dynamics simulations, we demonstrate that polyethylene (PE) self
      assembled monolayer (SAM) functionalized graphene surfaces at a high grafting
      density can drastically improve interfacial thermal conduction between graphene
      and the matrix of poly(methyl methacrylate) (PMMA). In contrast to abrupt
      temperature drop across pristine graphene/PMMA interfaces, temperature field in
      the vicinity of a PE-grafted graphene/PMMA interface is continuous with a
      smoother transition and higher thermal conductance. This anomalous improvement is
      attributed to three factors that closely relate to the grafting density of the
      SAM of PE. First, the SAM with high grafting densities features highly extended
      chains that enhance along-chain thermal conduction. Second, the strong covalent
      bonding between the SAM and the graphene facilitates heat transfer at their
      joints. Third, the SAM and the PMMA matrix are both organic materials, leading to
      enhanced interfacial vibrational coupling. Molecular mechanisms underpinning
      these phenomena are systematically elucidated by analyzing the temperature field,
      density distribution, Herman's orientation factor, the vibrational density of
      states, cumulative correlation factor, the integrated autocorrelation of
      interfacial heat power, and interfacial adhesion. All results suggest the
      incorporation of SAMs at a high grafting density or extremely extended polymer
      brushes for drastically improved interfacial thermal transport between hard and
      soft materials toward a wide range of applications.

PMID- 28766937
TI  - A Structural Basis for Biguanide Activity.
AB  - Metformin is the most commonly prescribed treatment for type II diabetes and
      related disorders; however, molecular insights into its mode(s) of action have
      been limited by an absence of structural data. Structural considerations along
      with a growing body of literature demonstrating its effects on one-carbon
      metabolism suggest the possibility of folate mimicry and anti-folate activity.
      Motivated by the growing recognition that anti-diabetic biguanides may act
      directly upon the gut microbiome, we have determined structures of the complexes
      formed between the anti-diabetic biguanides (phenformin, buformin, and metformin)
      and Escherichia coli dihydrofolate reductase (ecDHFR) based on nuclear magnetic
      resonance, crystallographic, and molecular modeling studies. Interligand
      Overhauser effects indicate that metformin can form ternary complexes with p
      aminobenzoyl-l-glutamate (pABG) as well as other ligands that occupy the region
      of the folate-binding site that interacts with pABG; however, DHFR inhibition is
      not cooperative. The biguanides competitively inhibit the activity of ecDHFR,
      with the phenformin inhibition constant being 100-fold lower than that of
      metformin. This inhibition may be significant at concentrations present in the
      gut of treated individuals, and inhibition of DHFR in intestinal mucosal cells
      may also occur if accumulation levels are sufficient. Perturbation of folate
      homeostasis can alter the pyridine nucleotide redox ratios that are important
      regulators of cellular metabolism.

PMID- 28766938
TI  - Rhenium and Technetium-oxo Complexes with Thioamide Derivatives of
      Pyridylhydrazine Bifunctional Chelators Conjugated to the Tumour Targeting
      Peptides Octreotate and Cyclic-RGDfK.
AB  - This research aimed to develop new tumor targeted theranostic agents taking
      advantage of the similarities in coordination chemistry between technetium and
      rhenium. A gamma-emitting radioactive isotope of technetium is commonly used in
      diagnostic imaging, and there are two beta- emitting radioactive isotopes of
      rhenium that have the potential to be of use in radiotherapy. Variants of the 6
      hydrazinonicotinamide (HYNIC) bifunctional ligands have been prepared by
      appending thioamide functional groups to 6-hydrazinonicotinamide to form
      pyridylthiosemicarbazide ligands (SHYNIC). The new bidentate ligands were
      conjugated to the tumor targeting peptides Tyr3-octreotate and cyclic-RGD. The
      new ligands and conjugates were used to prepare well-defined {M?O}3+ complexes
      (where M = 99mTc or natRe or 188Re) that feature two targeting peptides attached
      to the single metal ion. These new SHYNIC ligands are capable of forming well
      defined rhenium and technetium complexes and offer the possibility of using the
      99mTc imaging and 188/186Re therapeutic matched pairs.

PMID- 28766939
TI  - Hypoxia-Responsive Cobalt Complexes in Tumor Spheroids: Laser Ablation
      Inductively Coupled Plasma Mass Spectrometry and Magnetic Resonance Imaging
      Studies.
AB  - Dense tumors are resistant to conventional chemotherapies due to the unique tumor
      microenvironment characterized by hypoxic regions that promote cellular dormancy.
      Bioreductive drugs that are activated in response to this hypoxic environment are
      an attractive strategy for therapy with anticipated lower harmful side effects in
      normoxic healthy tissue. Cobalt bioreductive pro-drugs that selectively release
      toxic payloads upon reduction in hypoxic cells have shown great promise as
      anticancer agents. However, the bioreductive response in the tumor
      microenvironment must be better understood, as current techniques for monitoring
      bioreduction to Co(II) such as X-ray absorption near-edge structure and extended
      X-ray absorption fine structure provide limited information on speciation and
      require synchrotron radiation sources. Here, we present magnetic resonance
      imaging (MRI) as an accessible and powerful technique to monitor bioreduction by
      treating the cobalt complex as an MRI contrast agent and monitoring the change in
      water signal induced by reduction from diamagnetic Co(III) to paramagnetic
      Co(II). Cobalt pro-drugs built upon the tris(2-pyridylmethyl)amine ligand
      scaffold with varying charge were investigated for distribution and activity in a
      3D tumor spheroid model by laser ablation inductively coupled plasma mass
      spectrometry (LA-ICP-MS) and MRI. In addition, paramagnetic 1H NMR spectroscopy
      of spheroids enabled determination of the speciation of activated Co(II)TPAx
      complexes. This study demonstrates the utility of MRI and associated spectroscopy
      techniques for understanding bioreductive cobalt pro-drugs in the tumor
      microenvironment and has broader implications for monitoring paramagnetic metal
      based therapies.

PMID- 28766940
TI  - Cross Validation of Two Partitioning-Based Sampling Approaches in Mesocosms
      Containing PCB Contaminated Field Sediment, Biota, and Activated Carbon
      Amendment.
AB  - The Gold Standard for determining freely dissolved concentrations (Cfree) of
      hydrophobic organic compounds in sediment interstitial water would be in situ
      deployment combined with equilibrium sampling, which is generally difficult to
      achieve. In the present study, ex situ equilibrium sampling with multiple
      thicknesses of silicone and in situ pre-equilibrium sampling with low density
      polyethylene (LDPE) loaded with performance reference compounds were applied
      independently to measure polychlorinated biphenyls (PCBs) in mesocosms with (1)
      New Bedford Harbor sediment (MA, U.S.A.), (2) sediment and biota, and (3)
      activated carbon amended sediment and biota. The aim was to cross validate the
      two different sampling approaches. Around 100 PCB congeners were quantified in
      the two sampling polymers, and the results confirmed the good precision of both
      methods and were in overall good agreement with recently published LDPE to
      silicone partition ratios. Further, the methods yielded Cfree in good agreement
      for all three experiments. The average ratio between Cfree determined by the two
      methods was factor 1.4 +/- 0.3 (range: 0.6-2.0), and the results thus cross
      validated the two sampling approaches. For future investigations, specific aims
      and requirements in terms of application, data treatment, and data quality
      requirements should dictate the selection of the most appropriate partitioning
      based sampling approach.

PMID- 28766942
TI  - Author Gender and Career Progression in Environmental Science & Technology.

PMID- 28766943
TI  - Stabilizing g-States in Centrosymmetric Tetrapyrroles: Two-Photon-Absorbing
      Porphyrins with Bright Phosphorescence.
AB  - Using time-dependent density functional theory (TDDFT) and sum-overstates (SOS)
      formalism, we predicted significant stabilization of 2P-active g-states in a
      compact fully symmetric porphyrin, in which all four pyrrolic fragments are fused
      with phathalimide residues via the beta-carbon positions. The synthesis of a
      soluble, nonaggregating meso-unsubstituted tetraarylphthalimidoporphyrin (TAPIP)
      was then developed, and the spectroscopic measurements confirmed that a strongly
      2P-active state in this porphyrin is stabilized below the B (Soret) state level.
      Single-crystal X-ray analysis revealed near-ideally planar geometry of the TAPIP
      macrocycle, while its tetra-meso-arylated analogue (meso-Ar4TAPIP) was found to
      be highly saddled. Consistent with these structural features, Pt meso-Ar4TAPIP
      phosphoresces rather weakly (phiphos = 0.05 in DMF at 22  degrees C), while both
      Pt and Pd complexes of TAPIP are highly phosphorescent (phiphos = 0.45 and 0.23,
      respectively). In addition PdTAPIP exhibits non-negligible thermally activated (E
      type) delayed fluorescence (phifl(d) ~ 0.012). Taken together, these
      photophysical properties make metal complexes of meso-unsubstituted
      tetaarylphthalimidoporphyrins the brightest 2P-absorbing phosphorescent
      chromophores known to date.

PMID- 28766941
TI  - A Computational Investigation of Small-Molecule Engagement of Hot Spots at
      Protein-Protein Interaction Interfaces.
AB  - The binding affinity of a protein-protein interaction is concentrated at amino
      acids known as hot spots. It has been suggested that small molecules disrupt
      protein-protein interactions by either (i) engaging receptor protein hot spots or
      (ii) mimicking hot spots of the protein ligand. Yet, no systematic studies have
      been done to explore how effectively existing small-molecule protein-protein
      interaction inhibitors mimic or engage hot spots at protein interfaces. Here, we
      employ explicit-solvent molecular dynamics simulations and end-point MM-GBSA free
      energy calculations to explore this question. We select 36 compounds for which
      high-quality binding affinity and cocrystal structures are available. Five
      complexes that belong to three classes of protein-protein interactions (primary,
      secondary, and tertiary) were considered, namely, BRD4*H4, XIAP*Smac, MDM2*p53,
      Bcl-xL*Bak, and IL-2*IL-2Ralpha. Computational alanine scanning using MM-GBSA
      identified hot-spot residues at the interface of these protein interactions.
      Decomposition energies compared the interaction of small molecules with
      individual receptor hot spots to those of the native protein ligand.
      Pharmacophore analysis was used to investigate how effectively small molecules
      mimic the position of hot spots of the protein ligand. Finally, we study whether
      small molecules mimic the effects of the native protein ligand on the receptor
      dynamics. Our results show that, in general, existing small-molecule inhibitors
      of protein-protein interactions do not optimally mimic protein-ligand hot spots,
      nor do they effectively engage protein receptor hot spots. The more effective use
      of hot spots in future drug design efforts may result in smaller compounds with
      higher ligand efficiencies that may lead to greater success in clinical trials.

PMID- 28766944
TI  - Low-Temperature Solution Synthesis of Transition Metal Dichalcogenide Alloys with
      Tunable Optical Properties.
AB  - Nanostructures of layered transition metal dichalcogenide (TMD) alloys with
      tunable compositions are promising candidates for a broad scope of applications
      in electronics, optoelectronics, topological devices, and catalysis. Most TMD
      alloy nanostructures are synthesized as films on substrates using gas-phase
      methods at high temperatures. However, lower temperature solution routes present
      an attractive alternative with the potential for larger-scale, higher-yield
      syntheses of freestanding, higher surface area materials. Here, we report the
      direct solution synthesis of colloidal few-layer TMD alloys, MoxW1-xSe2 and
      WS2ySe2(1-y), exhibiting fully tunable metal and chalcogen compositions that span
      the MoSe2-WSe2 and WS2-WSe2 solid solutions, respectively. Chemical guidelines
      for achieving the targeted compounds are presented, along with comprehensive
      structural characterizations (X-ray diffraction, electron microscopy, Raman, and
      UV-visible spectroscopies). High-resolution microscopic imaging confirms the
      formation of TMD alloys and identifies a random distribution of the alloyed
      elements. Analysis of the tilt-angle dependency of the intensities associated
      with atomic-resolution annular dark field imaging line scans reveals the types of
      point vacancies present in the samples, thus providing atomic-level insights into
      the structures of colloidal TMD alloy nanostructures that were previously only
      accessible for substrate-confined films. The A excitonic transition of the TMD
      alloy nanostructures can be readily adjusted between 1.51 and 1.93 eV through
      metal and chalcogen alloying, correlating the compositional modulation to the
      realization of tunable optical properties.

PMID- 28766945
TI  - Mononuclear Rhodium(II) and Iridium(II) Complexes Supported by Tetradentate
      Pyridinophane Ligands.
AB  - The tetradentate ligands N,N'-dialkyl-2,11-diaza[3,3](2,6)pyridinophane (RN4,
      where R = Me or tBu) were employed to synthesize and fully characterize
      [(RN4)MI(COD)]+ complexes (M = Rh or Ir; COD = cyclooctadiene). Interestingly,
      these complexes exhibit accessible oxidation potentials and can generate
      detectable [(RN4)MII(COD)]2+ complexes, which were characterized by electron
      paramagnetic resonance and high-resolution electrospray ionization mass
      spectrometry. Moreover, a rare mononuclear [(MeN4)RhII(COD)]2+ complex was
      isolated and crystallographically characterized, allowing for a direct comparison
      with its rhodium(I) analogue. The detailed characterization of such paramagnetic
      rhodium(II) and iridium(II) complexes enables further investigation of their
      redox reactivity.

PMID- 28766946
TI  - Structural and Dielectric Relaxations in Vitreous and Liquid State of Monohydroxy
      Alcohol at High Pressure.
AB  - 2-Ethyl-1-hexanol monoalcohol is a well-known molecular glassformer, which for a
      long time attracts attention of researchers. As in all other monohydroxy
      alcohols, its dielectric relaxation reveals two distinct relaxation processes
      attributed to the structural relaxation and another more intense process, which
      gives rise to a low-frequency Debye-like relaxation. In this monoalcohol, the
      frequency separation between these two processes reaches an extremely high value
      of 3 orders of magnitude, which makes this substance a rather convenient object
      for studies of mechanisms (supposedly common to all monoalcohols) leading to
      vitrification of this type of liquids. In this work, we apply two experimental
      techniques, dielectric spectroscopy and ultrasonic measurements (in both
      longitudinal and transverse polarizations) at high pressure, to study
      interference between different relaxation mechanisms occurring in this liquid,
      which could shed light on both structural and dielectric relaxation processes
      observed in a supercooled liquid and a glass state. Application of high pressure
      in this case leads to the simplification of the frequency spectrum of dielectric
      relaxation, where only one asymmetric feature is observed. Nonetheless, the
      maximum attenuation of the longitudinal wave in ultrasonic experiments at high
      pressure is observed at temperatures ~50 K above the corresponding temperature
      for the transverse wave. This might indicate different mechanisms of structural
      relaxation in shear and bulk elasticities in this liquid.

PMID- 28766947
TI  - Creatine Monohydrate Enhances Energy Status and Reduces Glycolysis via Inhibition
      of AMPK Pathway in Pectoralis Major Muscle of Transport-Stressed Broilers.
AB  - Creatine monohydrate (CMH) contributes to reduce transport-induced muscle rapid
      glycolysis and improve meat quality of broilers, but the underlying mechanism is
      still unknown. Therefore, this study aimed to investigate the molecular
      mechanisms underlying the ameliorative effects of CMH on muscle glycolysis
      metabolism of transported broilers during summer. The results showed that 3 h
      transport during summer elevated chicken live weight loss and plasma
      corticosterone concentration; decreased muscle concentrations of ATP, creatine,
      and energy charge value; increased muscle AMP concentration and AMP/ATP ratio;
      and upregulated muscle mRNA expression of LKB1 and AMPKalpha2, as well as protein
      expression of p-LKB1Thr189 and p-AMPKalphaThr172, which subsequently resulted in
      rapid glycolysis in the pectoralis major muscle and consequent reduction of meat
      quality. Dietary addition of CMH at 1200 mg/kg ameliorated transport-induced
      rapid muscle glycolysis and reduction of meat quality via enhancement of the
      energy-buffering capacity of intramuscular phosphocreatine/creatine system and
      inhibition of AMPK pathway.

PMID- 28766948
TI  - Organic Dye-Catalyzed Atom Transfer Radical Addition-Elimination (ATRE) Reaction
      for the Synthesis of Perfluoroalkylated Alkenes.
AB  - An atom transfer radical addition elimination (ATRE) reaction of terminal alkenes
      with perfluoroalkyl halides under visible light is described. The photoredox
      catalysis with Eosin Y provides perfluoroalkenes in good yields. The reaction has
      been utilized for the late stage perfluoroalkenylation of an estrone-derived
      alkene.

PMID- 28766949
TI  - A Gram-Scale HPLC-Free Synthesis of TNA Triphosphates Using an Iterative
      Phosphorylation Strategy.
AB  - alpha-l-Threofuranosyl nucleoside 3'-triphosphates (tNTPs) bearing the four
      genetic bases adenine (A), cytosine (C), guanine (G), and thymine (T) were
      synthesized on a gram scale using an iterative phosphorylation strategy that
      avoids the need for tedious HPLC purification. This new synthetic procedure
      greatly increases the scale on which tNTP substrates can be produced for
      polymerase-mediated TNA synthesis studies.

PMID- 28766951
TI  - Therapy for Clostridium difficile infection - any news beyond Metronidazole and
      Vancomycin?
AB  - INTRODUCTION: Infections with Clostridium difficile (CDI) represent a major
      burden for the health care system. Treatment is generally by antibiotic therapy
      with metronidazole and vancomycin, but efficacy remains suboptimal. Areas
      covered: This review discusses established and emerging treatment options for
      CDI, and current therapeutic guidelines, taking into account disease severity and
      risk of relapse. Expert commentary: New therapeutic approaches, including
      antibodies and new classes of antibiotics, and new measures for preventing
      infection with vaccines are under development in phase II/III clinical trials. We
      performed a systematic literature review using the search terms 'Clostridium
      difficile' and 'treatment'.

PMID- 28766950
TI  - Imaging features of rare mesenychmal liver tumours: beyond haemangiomas.
AB  - Tumours arising from mesenchymal tissue components such as vascular, fibrous and
      adipose tissue can manifest in the liver. Although histopathology is often
      necessary for definitive diagnosis, many of these lesions exhibit characteristic
      imaging features. The radiologist plays an important role in suggesting the
      diagnosis, which can direct appropriate immunohistochemical staining at
      histology. The aim of this review is to present clinical and imaging findings of
      a spectrum of mesenchymal liver tumours such as haemangioma, epithelioid
      haemangioendothelioma, lipoma, PEComa, angiosarcoma, inflammatory myofibroblastic
      tumour, solitary fibrous tumour, leiomyoma, leiomyosarcoma, Kaposi sarcoma,
      mesenchymal hamartoma, undifferentiated embryonal sarcoma, rhabdomyosarcoma and
      hepatic metastases. Knowledge of the characteristic features of these tumours
      will aid in guiding the radiologic diagnosis and appropriate patient management.

PMID- 28766953
TI  - Working with a fractional object: enactments of appetite in interdisciplinary
      work in anthropology and biomedicine.
AB  - This paper explores the productive tensions occurring in an interdisciplinary
      research project on weight loss after obesity surgery. The study was a bio
      medical/anthropological collaboration investigating to what extent eating
      patterns, the subjective experience of hunger and physiological mechanisms are
      involved in appetite regulation that might determine good or poor response to the
      surgery. Linking biomedical and anthropological categories and definitions of
      central concepts about the body turned out to be a major challenge in the
      collaborative analysis. Notably, the conception of what constitutes 'appetite'
      was a key concern, as each discipline has its particular definition and
      operationalization of the term. In response, a material-semiotic approach was
      chosen which allowed for a reconceptualization of appetite as a 'fractional
      object', engaged in multiple relations and enacted differently in each instance.
      This perspective produced creative contrasts and offered alternative explorations
      of both scientific knowledge production and anthropological practices. The paper
      thereby explores the interfaces between anthropology and medical science by
      attending to the challenges and opportunities that result from destabilising an
      assumed fixed and well-defined concept associated with the body.

PMID- 28766952
TI  - Inhibition of the beta-carbonic anhydrase from the dandruff-producing fungus
      Malassezia globosa with monothiocarbamates.
AB  - A series of monothiocarbamates (MTCs) was investigated for the inhibition of the
      beta-class carbonic anhydrase (CAs, EC 4.2.1.1) from the fungal parasite
      Malassezia globosa, MgCA. These MTCs incorporate various scaffolds, among which
      aliphatic amine with 1-4 carbons atom in their molecule, morpholine, piperazine,
      as well as phenethylamine and benzylamine derivatives. All the reported MTCs
      displayed a better efficacy in inhibiting MgCA compared to the clinically used
      sulphonamide drug acetazolamide (KI of 74 MUM), with KIs spanning between 1.85
      and 18.9 MUM. The homology model of the enzyme previously reported by us was used
      to rationalize the results by docking some of these MTCs within the fungal CA
      active site. This study might be useful to enrich the knowledge of the MgCA
      inhibition profile, eliciting novel ideas pertaining the design of modulators
      with potential efficacy in combatting dandruff or other fungal infections.

PMID- 28766954
TI  - Dysphagia in Rett Syndrome: A Descriptive Study.
AB  - OBJECTIVES: Rett syndrome (RS) is a neurodevelopmental disorder and the second
      major cause of mental retardation in females. The aim of this study was to
      evaluate swallowing problems of RS patients by endoscopic assessment and compile
      a list of suggestions for managing feeding and preventing complications. METHODS:
      The sample consisted of 61 female patients (mean age = 13.6 years, range, 2-33
      years) admitted to the Department of Neuropsychiatry, where they had previously
      been diagnosed with RS. Speech evaluation associated with observation during
      mealtimes was useful to formulate suggestions for caregivers. RESULTS:
      Progressive deterioration of feeding was commonly noted by caregivers. Fifty-four
      patients had a history of recurrent episodes of bronchitis. Oral apraxia,
      dyskinetic tongue movements, prolonged oral stage, and poor bolus formation were
      the most common findings in all patients. CONCLUSIONS: Dysphagia was primarily
      limited to oral preparatory phases, while the pharyngeal phase was normal in most
      patients. The high percentage of dysphagia suggests the need to accurately
      monitor the feeding capability of RS children. It is critical to correctly inform
      caregivers about safe swallowing procedures to reduce the incidence of fatal
      complications.

PMID- 28766955
TI  - Risk Factors of Stomal Recurrence After Laryngectomy: A Systematic Review and
      Meta-analysis.
AB  - OBJECTIVE: We wished to investigate the risk factors for stoma recurrence
      following laryngectomy. METHODS: PubMed, Cochrane Library, and Embase were
      searched to identify primary research studies published between January 1, 1967,
      and October 31, 2016. We only included observational epidemiological studies and
      used risk ratios (RRs) and 95% confidence intervals (CI) to summarize the primary
      risk factors associated with recurrence following laryngectomy. RESULTS: A total
      of 44 articles, including 11 928 patients, were included in the current meta
      analysis. The pooled estimates of the stomal recurrence rate and the local
      recurrence rate following laryngectomy were 6.60% (95% CI, 5.40-7.90) and 19.40%
      (95% CI, 14.00%-24.80%), respectively. For stomal recurrence, we confirmed a
      series of earlier identified factors, including tumor site, prior tracheotomy,
      tracheotomy timing, T-classification, lymph node metastases, postoperative
      pharyngoperistomal fistula, and a positive surgical margin. For local recurrence,
      postoperative radiotherapy, overexpression of p53, and overexpression of p21 were
      significant, while preoperative tracheostomy and postoperative pharyngoperistomal
      fistula had an unexpectedly low impact on risk. CONCLUSION: This study has
      confirmed a series of earlier identified factors for stomal recurrence and local
      recurrence following laryngectomy. Our results will provide important insights
      for clinical practice.

PMID- 28766956
TI  - Design and synthesis of benzopyran-based inhibitors of the hypoxia-inducible
      factor-1 pathway with improved water solubility.
AB  - While progress has been made in treating cancer, cytotoxic chemotherapeutic
      agents are still the most widely used drugs and are associated with severe side
      effects. Drugs that target unique molecular signalling pathways are needed for
      treating cancer with low or no intrinsic toxicity to normal cells. Our goal is to
      target hypoxic tumours and specifically the hypoxia inducible factor (HIF)
      pathway for the development of new cancer therapies. To this end, we have
      previously developed benzopyran-based HIF-1 inhibitors such as arylsulfonamide
      KCN1. However, KCN1 and its earlier analogs have poor water solubility, which
      hamper their applications. Herein, we describe a series of KCN1 analogs that
      incorporate a morpholine moiety at various positions. We found that replacing the
      benzopyran group of KCN1 with a phenyl group with a morpholinomethyl moiety at
      the para positions had minimal effect on potency and improved the water
      solubility of two new compounds by more than 10-fold compared to KCN1, the lead
      compound.

PMID- 28766957
TI  - Immunohistochemical detection of C9orf72 protein in frontotemporal lobar
      degeneration and motor neurone disease: patterns of immunostaining and an
      evaluation of commercial antibodies.
AB  - We have employed as 'gold standards' two in-house, well-characterised and
      validated polyclonal antibodies, C9-L and C9-S, which detect the longer and
      shorter forms of C9orf72, and have compared seven other commercially available
      antibodies with these in order to evaluate the utility of the latter as credible
      tools for the demonstration of C9orf72. C9-L and C9-S antibodies immunostained
      cytoplasmic 'speckles', and the nuclear membrane, respectively, in cerebellar
      Purkinje cells of the cerebellum in patients with behavioural variant
      frontotemporal dementia (bvFTD) with amyotrophic lateral sclerosis (ALS), and in
      patients with ALS alone. Similar staining was seen in Purkinje cells in healthy
      control tissues and in other neurodegenerative disorders, and in pyramidal cells
      of CA4 and dentate gyrus of hippocampus. However, in the spinal cord there was
      little cytoplasmic staining with C9-L antibody. C9-S antibody immunostained the
      nuclear membrane of anterior horn cells in healthy neurons. In patients with
      bvFTD + ALS, or ALS alone, this C9-S nuclear staining was redistributed to the
      plasma membrane. In those patients with bvFTD + ALS or ALS bearing an expansion
      in C9orf72, none of the commercially available antibodies detected TDP-43
      inclusions in anterior horn cells, nor were dipeptide repeat proteins
      demonstrated. Five of the commercial antibodies provided immunohistochemical
      staining patterns similar in morphological appearance to the in-house C9-L
      antibody, but distinct from C9-S antibody. However, only three showed sufficient
      specificity and intensity of staining for C9orf72 at acceptably low
      concentrations, to make them of practical value and sufficiently reliable for the
      detection of at least the longer form of C9orf72 protein.

PMID- 28766958
TI  - The "Acute" Stone Clinic Effect: Improving Healthcare Delivery by Reorganizing
      Clinical Resources.
AB  - OBJECTIVE: To determine the time to specialist urologic consultation and
      definitive management after establishing a subspecialist administered acute stone
      clinic (ASC) for adults with symptomatic upper tract stones in a publically
      funded universal healthcare system. MATERIALS AND METHODS: We retrospectively
      reviewed 337 adult referrals for stone management. Three distinct 9-week periods
      were assessed. Group 1 patients were seen/treated by their individual urologist
      before inception of a general urology emergency clinic (pre-EC). Group 2 patients
      were seen in a pooled EC and Group 3 patients were seen in the ASC. RESULTS: A
      total of 337 patients (75, pre-EC; 91, EC; 171, ASC) were reviewed. Mean time to
      consultation for pre-EC, EC, and ASC cohorts was 29, 7, and 7 days, respectively
      (p < 0.05), whereas loss to follow-up decreased from 13% to 5% (p < 0.05). On
      average, the number of patients seen per week increased from 9 to 20. Mean time
      to stone surgery from date of referral was 75 days pre-EC, 43 days EC, and 25
      days ASC (p < 0.05). The percentage of patients undergoing surgery was between
      59% and 63% per cohort; however, the number of patients increased from 5 to 11
      per week. CONCLUSIONS: By reorganizing clinical resources, a dedicated ASC was
      able to increase patient capacity, reduce time to urologist consultation and
      reduce surgical wait times.

PMID- 28766959
TI  - Pediatric Chronic Rhinosinusitis Management in Rhinologists and Pediatric
      Otolaryngologists.
AB  - OBJECTIVE: To compare the management of pediatric chronic rhinosinusitis (PCRS)
      between members of the American Rhinologic Society (ARS) and the American Society
      of Pediatric Otolaryngology (ASPO). STUDY DESIGN: Comparison of surveys. METHODS:
      A web-based survey was distributed to ASPO membership twice in September-October
      2016. Data were compared to previously published data from ARS membership in
      March-April 2016. RESULTS: ASPO survey completion rate was 22%. ARS members were
      more likely to employ oral steroids in initial ( P = .025) and maximal medical
      management ( P = .001). ASPO members more commonly performed adenoidectomy before
      computed tomography (CT) ( P < .001). Both groups commonly included adenoidectomy
      as part of initial surgical management (90% vs 94%, P = .316), while ASPO members
      more frequently performed adenoidectomy alone (70% vs 43%, P = .001). If initial
      surgical treatment failed, both groups commonly performed endoscopic sinus
      surgery (ESS; 81% vs 88%, P = .56) with a similar extent including frontal ( P >=
      .207) and sphenoid ( P >= .304) surgery. CONCLUSIONS: Pediatric chronic
      rhinosinusitis management is similar between groups, yet there are differences
      including oral steroid use, relative order of CT versus adenoidectomy, and
      performing concomitant procedures with adenoidectomy. Both groups commonly
      perform ESS with similar surgical extent if prior surgical treatment fails.
      Management by both groups is largely in agreement with published consensus
      statements.

PMID- 28766960
TI  - The Acceptable Criterion of Stone Burden and the Significant Factors to Choose
      Retrograde Intrarenal Stone Surgery or Miniaturized Percutaneous Nephrolithotomy
      for the Treatment of Renal Stones >10 mm.
AB  - OBJECTIVE: We investigated the surgical efficiency and cutoff criteria to
      determine whether retrograde intrarenal surgery (RIRS) or supine miniaturized
      percutaneous nephrolithotomy (MPCNL) is appropriate for managing renal stones
      with a mean size >10 mm. MATERIALS AND METHODS: Data of a single session RIRS or
      supine MPCNL were collected in a prospective, observational study. Change point
      analysis with a cumulative sum of ordered value of fragmentation efficiency and
      stone size was used to detect the point at which the statistical properties of a
      sequence of observation change. RESULTS: A total of 310 RIRS and 66 MPCNL cases
      were included. No differences in patient characteristics were observed between
      the groups. Stone burden, fragmentation efficiency, stone distribution, and the
      presence of staghorn stones were higher in the MPCNL group than the RIRS group.
      Stone-free rates and complication rates were not different. The fragmentation
      efficiency increased to 40.4 mL/min, at which the stone size in the RIRS group
      was 19.1 mm. The efficiency was decreased after the peak point and became the
      same at the stone size 30 mm with 10 mm in RIRS group. The fragmentation
      efficiency in the MPCNL group continuously increased until the size of 35.1 mm.
      CONCLUSIONS: RIRS shows the highest efficiency at the maximal diameter of 19.1 mm
      and volume of 15,000 mm3. The acceptable level of stone size and volume for RIRS
      would be 30.0 mm and 27,000 mm3, respectively. However, MPCNL would be
      appropriate when surgeons want to get high surgical efficiency for renal stone
      >21.6 mm instead of RIRS.

PMID- 28766961
TI  - HOXA13 is associated with unfavorable survival and acts as a novel oncogene in
      prostate carcinoma.
AB  - AIM: To investigate the clinical relevance and functional role of HOXA13 in
      prostate cancer Methods: PCR, western blot and immunohistochemistry were
      performed to determine the expression. Kaplan-Meier and Cox regression survival
      analyses investigated the clinical relevance. Cell viability, flow cytometry and
      transwell assays were used to determine the functional roles. RESULTS: HOXA13
      expression is sharply increased in carcinoma tissues and is significantly
      associated with poor prognosis of prostate cancer patients. Interestingly,
      nucleus not cytoplasm HOXA13 expression is associated with unfavorable survival
      of the patients. Furthermore, nucleus HOXA13 expression represents an unfavorable
      and independent prognosis factor of histological grade 2 or Gleason grade <8
      patients. Functionally, forced expression of HOXA13 obviously promotes tumor cell
      proliferation, migration and invasion, whereas inhibits tumor cell apoptosis.
      CONCLUSION: HOXA13 is an unfavorable prognostic factor and a novel oncogene for
      prostate cancer.

PMID- 28766963
TI  - A proposal for the inclusion of 'obesity dysmorphia' in the Diagnostic and
      Statistical Manual of Mental Disorders.

PMID- 28766965
TI  - MAP2 IHC detection: a marker of antigenicity in CNS tissues.
AB  - Immunohistochemistry (IHC) is used to detect antibody-specific antigens in
      tissues; the results depend on the ability of the primary antibodies to bind to
      their antigens. Therefore, results depend on the quality of preservation of the
      specimen. Many investigators have overcome the deleterious effects of over
      fixation on the binding of primary antibodies to specimen antigens using IHC, but
      if the specimen is under-fixed or fixation is delayed, false negative results
      could be obtained despite certified laboratory practices. Microtubule-associated
      protein 2 (MAP2) is an abundant microtubule-associate protein that participates
      in the outgrowth of neuronal processes and synaptic plasticity; it is localized
      primarily in cell bodies and dendrites of neurons. MAP2 immunolabeling has been
      reported to be absent in areas of the entorhinal cortex and hippocampus of
      Alzheimer's disease brains that were co-localized with the dense-core type of
      amyloid plaques. It was hypothesized that the lack of MAP2 immunolabeling in
      these structures was due to the degradation of the MAP2 antigen by the neuronal
      proteases that were released as the neurons lysed leading to the formation of
      these plaques. Because MAP2 is sensitive to proteolysis, we hypothesized that
      changes in MAP2 immunolabeling may be correlated with the degree of fixation of
      central nervous system (CNS) tissues. We detected normal MAP2 immunolabeling in
      fixed rat brain tissues, but MAP2 immunolabeling was decreased or lost in unfixed
      and delayed-fixed rat brain tissues. By contrast, two ubiquitous CNS-specific
      markers, myelin basic protein and glial fibrillary acidic protein, were
      unaffected by the degree of fixation in the same tissues. Our observations
      suggest that preservation of various CNS-specific antigens differs with the
      degree of fixation and that the lack of MAP2 immunolabeling in the rat brain may
      indicate inadequate tissue fixation. We recommend applying MAP2 IHC for all CNS
      tissues as a pre-screen to assess the quality of the tissue preservation and to
      avoid potentially false negative IHC results.

PMID- 28766964
TI  - Boosting anti-HER2 CD4 T-helper responses in HER2 expressing ductal carcinoma in
      situ.

PMID- 28766966
TI  - Age- and sex-related differences in the presentation of paediatric migraine: A
      retrospective cohort study.
AB  - Introduction Although migraine is a common headache complaint in children and
      adolescents there remains a significant gap in understanding the unique aspects
      of the disease in these age groups and their evolution with development. The aim
      of this retrospective cohort study was to identify migraine features that are
      influenced by age and sex. Methods The headache characteristics of 359 paediatric
      patients with a clinical diagnosis of migraine from a tertiary paediatric
      headache clinic were assessed. Patients retrospectively reported headache
      characteristics during a structured intake interview and clinical exam. Headache
      characteristics, description and associated symptoms were compared between
      children (age <= 12 years) and adolescents (age > 12 years), and between male and
      female migraineurs. Results Several migraine features differed significantly with
      age and/or sex, including: (i) a marked change from a 1:1 sex ratio in children
      to a 2:1 predominance of girls in adolescents; (ii) a higher frequency of
      headache attacks per month in adolescents and female migraineurs; (iii) a higher
      proportion of adolescents endorsed a 'throbbing' pain quality; (iv) a higher
      proportion of children reporting nausea and vomiting; and (v) a higher proportion
      of adolescents, particularly female migraineurs, had a diagnosis of a co-morbid
      anxiety. Conclusion The presentation of migraine, both in terms of its headache
      characteristics and associated symptoms, appear to vary as a function of age and
      sex. Given that migraine symptoms have a neural basis, it is not surprising that
      during the key period of neurodevelopment from childhood to adolescence this may
      impact their presentation.

PMID- 28766962
TI  - Clarifying busulfan metabolism and drug interactions to support new therapeutic
      drug monitoring strategies: a comprehensive review.
AB  - INTRODUCTION: Busulfan (Bu) is an alkylating agent with a limited therapeutic
      margin and exhibits inter-patient variability in pharmacokinetics (PK). Despite
      decades of use, mechanisms of Bu PK-based drug-drug interactions (DDIs), as well
      as the negative downstream effects of these DDIs, have not been fully
      characterized. Areas covered: This article provides an overview of Bu PK, with a
      primary focus on how known and potentially unknown drug metabolism pathways
      influence Bu-associated DDIs. In addition, pharmacogenomics of Bu chemotherapy
      and Bu-related DDIs observed in the stem cell transplant clinic (SCT) are
      summarized. Finally the increasing importance of Bu therapeutic drug monitoring
      is highlighted. Expert opinion: Mechanistic studies of Bu metabolism have shown
      that in addition to GST isoenzymes, other oxidative enzymes (CYP, FMO) and
      ABC/MDR drug transporters likely contribute to the overall clearance of Bu.
      Despite many insights, results from clinical studies, especially in polypharmacy
      settings and between pediatric and adult patients, remain conflicting. Further
      basic science and clinical investigative efforts are required to fully understand
      the key factors determining Bu PK characteristics and its effects on
      complications after SCT. Improved TDM strategies are promising components to
      further investigate, for instance DDI mechanisms and patient outcomes, in the
      highly complex SCT treatment setting.

PMID- 28766967
TI  - Regorafenib as treatment for patients with advanced hepatocellular cancer.
AB  - Hepatocellular carcinoma is one of the fastest growing causes of cancer-related
      mortality worldwide. Sorafenib was the first and only drug to improve survival
      for patients with advanced disease, and has been the cornerstone of treatment for
      nearly a decade. Regorafenib is a multikinase inhibitor that has recently been
      shown to significantly improve survival in patients who have progressed on first
      line sorafenib. In this review, we discuss the pharmacokinetic and
      pharmacodynamics properties of regorafenib and its efficacy and tolerability in
      patients with advanced hepatocellular carcinoma.

PMID- 28766968
TI  - Newspaper coverage of Alzheimer's disease: Comparing online newspapers in Hebrew
      and Arabic across time.
AB  - The aim of the present study was to examine the objective characteristics and the
      portrayal of Alzheimer's disease and of persons with Alzheimer's disease in
      Hebrew and Arabic online newspapers across time. The sample included 180 articles
      published in seven national online newspapers between 2010-2011 and 2014-2015 and
      dealing specifically with the topic. The majority of the articles in both periods
      and languages were published in the Health section of the newspapers, had a
      neutral tone, and experts or researchers as the main sources of information.
      Stigmatizing elements were infrequent. While small differences were found across
      time, significant differences were found between Hebrew and Arabic online
      newspapers, with Arabic newspapers concentrating more on objective, health
      related and expert-based information. As the use of online newspapers increases,
      policy makers should consider the use of this media as a viable way for improving
      knowledge and awareness about AD and dementia.

PMID- 28766969
TI  - Meta-analysis of clinical significance of p53 protein expression in patients with
      osteosarcoma.
AB  - AIM: The prognostic role of p53 protein expression in osteosarcoma has been
      reported, but the results remain conflicting. MATERIALS & METHODS: The relevant
      literature databases were searched to get eligible articles published in English.
      The overall ORs or HRs and their corresponding 95% CIs were calculated. RESULTS:
      The results indicated that p53 protein expression was not linked to age factor,
      gender, tumor grade, cancer metastasis and response to chemotherapy. p53
      expression was significantly lower in osteogenic osteosarcoma than in
      nonosteogenic osteosarcoma (OR = 0.40; p = 0.006). p53 expression was associated
      with a poor prognosis of patients in overall survival (univariate analysis: HR:
      2.49; p < 0.001 and multivariate analysis: HR: 2.92; p < 0.001). CONCLUSION: p53
      expression was correlated with pathological type and may become a useful
      prognostic biomarker in overall survival in osteosarcoma.

PMID- 28766970
TI  - Effect of polyphenols from Vicia faba L on lipase activity and melanogenesis.
AB  - Two new flavonoid glycosides, kaempferol 3-O-alpha-L-rhamnopyranosyl (1->6) (3''
      acetyl)-beta-D-galactopyranoside 1 and kaempferol 3-O-alpha-L-arabinopyranosyl-5
      O-alpha-L-rhamnopyranoside 2, along with six known ones 3-8 were isolated from
      the flowers of Vicia faba L. (Fabaceae). Methanol extract and the isolated
      compounds were tested against lipase and melanogenesis inhibition activities and
      resulted in that compound 2 showed 53 and 77% lipase inhibition activity in
      concentrations of 400 and 800 MUg/mL, respectively. For melanogenesis, compounds
      2, 3 and 4 exhibited potent melanogenesis inhibition activity where the melanin
      content in melanoma cells was decreased to be about 57.5, 56 and 61%,
      respectively, with no obvious melanocytotoxicity. The rest of compounds showed
      weak to moderate activity. The results of melanogenesis inhibition activity of
      this study suggested the potential use of Vicia faba flowers as a skin-whitening
      agent and reveal the flowers to be a rich source of important phytochemicals with
      antilipase and melanogenesis inhibitory activity.

PMID- 28766971
TI  - A Concept Analysis of Resilience Integrating Genetics.
AB  - Although clinicians and researchers are interested in the phenomenon of
      resilience, there is no agreed-upon definition of resilience. Scientific evidence
      suggests that resilience is influenced by intrapersonal (e.g. personality traits)
      and environmental (e.g. social support) variables. A concept analysis was
      conducted to better understand the meaning of resilience. In this analysis, the
      antecedent of resilience was a potentially traumatic event; the defining
      attributes were ego-resiliency, emotion regulation, social support, and heredity;
      and the consequences were none to mild psychopathological symptoms and positive
      adaptation. This analysis can help nurses better understand resilience and its
      relationships to both intrapersonal and environmental variables.

PMID- 28766972
TI  - "Coming Out" with a Mental Disorder in Japan: How Self-Stigma and Empowerment
      Affect this Decision.
AB  - When persons with mental disorders attempt to live independently in the
      community, they face situations where they must decide whether to disclose their
      disorder (i.e., "come out"), which will affect self-concept, self-stigma, and
      empowerment. We conducted a self-reported questionnaire among users of
      psychiatric daycare facilities (N = 150) to gather correlational data on these
      variables among others. Sixty-one percent had positive intentions to come out,
      which was influenced by affirmativeness and self-efficacy. More participants with
      mood disorders intended on coming out than did those with schizophrenia.
      Satisfaction with social support encouraged coming-out affirmativeness and
      autonomy, providing implications for caregivers.

PMID- 28766973
TI  - Assessment of Mental Health Literacy among Perinatal Hispanic Adolescents.
AB  - According to the United States (U.S.) Census Bureau, Hispanics are the fastest
      growing ethnic minority in the U.S. As such, Hispanic females have the highest
      birth rate (35 per 1000) among adolescents between the ages of 15 and 19 years.
      Despite high fertility rates, there is limited mental health information among
      Hispanic adolescents during the perinatal period. Perinatal depression is a major
      concern as it poses health risks for both the mother and infant. Adverse outcomes
      such as preterm birth, low infant birth weight, and poor maternal-infant
      attachment may result from perinatal depression. However, less than half of
      Hispanic adolescent mothers who experience perinatal depression receive
      treatment. Previous research identified low mental health literacy (MHL) as one
      of the primary reasons for the limited use of mental health services among ethnic
      minorities. This study assessed the MHL of pregnant and postpartum Hispanic
      adolescents (n = 30) using a modified MHL scale. Implications for nursing
      practice are discussed to help improve mental health outcomes among pregnant and
      postpartum Hispanic adolescents.

PMID- 28766974
TI  - The Experiences of Clinicians Caring for Older Adults with Dual Diagnosis: An
      Exploratory Study.
AB  - Dual diagnosis has been identified as a significant challenge to mental health
      services, resulting in higher rates of psychiatric relapse and greater illness
      severity. Much research explores dual diagnosis in the adult mental health
      cohort, however little research attention has been paid to older adults with dual
      diagnosis. Far from being a trivial issue, preliminary studies have shown that
      dual diagnosis in older adults is under diagnosed and poorly identified by
      clinicians with few specific treatment options available. In addition, studies of
      the ageing baby boomer cohort demonstrate a potential for dual diagnosis
      presentations to increase in the coming years. This article explores the
      experiences of a clinical team providing care to older adults with dual diagnosis
      in Melbourne, Australia, through a semi-structured interview process. The
      participants described a number of systemic barriers to providing care to the
      older adults with dual diagnosis presenting to the mental health service, in
      addition to feeling poorly prepared and expressing a degree of clinical
      helplessness. Additionally, the participants described service improvement, which
      included a strong dual diagnosis culture in the leadership team of the mental
      health service and role modelling dual diagnosis competent practice among
      clinicians.

PMID- 28766975
TI  - Factors Associated with Potential Drug-Drug Interactions in Patients Attended in
      Primary Health Care: A Focus on Mental Health.
AB  - : There were no Brazilian studies regarding potential drug-drug interactions
      (DDIs) in primary health care (PHC) analysing common mental disorders (CMDs) and
      psychotropic medication. OBJECTIVES: To identify DDI prevalence in that setting;
      to classify DDI; to verify correlations with demographics, pharmacotherapeutics,
      psychotropic medication and CMDs. Among 430 patients interviewed 190 had more
      than two medications prescribed, 58.4% had DDI. Factors associated were age and
      number of medications. Nine types of severe DDI composed 28% patients'
      prescriptions, 71.9% involving psychotropic medication. Only the number of types
      of drugs contributed to the regression model. Results raise important aspects
      regarding patient safety in PHC units in Brazil are where patients with
      psychological complaints have to seek for health care firstly.

PMID- 28766976
TI  - PHEDRA: using real-world data to analyze treatment patterns and ibrutinib
      effectiveness in hematological malignancies.
AB  - AIM: PHEDRA (Platform for Haematology in EMEA: Data for Real World Analysis) is a
      unique, noninterventional project based on secondary data collection from real
      world (RW) patient-level (health record) databases to understand treatment
      patterns in hematological malignancies. It compares ibrutinib's effectiveness
      with alternative treatments using RW data (RWD) and randomized clinical trials
      data. MATERIALS & METHODS: RWD are cleaned, validated, harmonized into a Common
      Data Model, and analyzed statistically alongside randomized clinical trial data.
      Treatment outcomes include overall and progression-free survival. RESULTS: To
      date, RWD (four databases) are available for 2840 patients in three indications,
      collected between 1990 and 2017. CONCLUSION: PHEDRA is an innovative approach to
      generate evidence to inform optimal treatment decisions in RW settings.

PMID- 28766977
TI  - Surgical Management of Supraglottic Stenosis Using Intubationless Optiflow.
AB  - OBJECTIVE: Airway management during endoscopic surgical treatment of supraglottic
      and pharyngeal stenosis is often challenging and can be accomplished by various
      means, including tracheostomy, jet ventilation, or direct laryngoscopy. We
      describe CO2 laser excision of supraglottic-pharyngeal stenosis using
      intubationless Optiflow high-flow nasal cannula (HFNC). METHODS: A 55-year-old
      male presented with dyspnea and dysphagia secondary to severe supraglottic
      pharyngeal stenosis in the setting of previous chemoradiation for a T0N2aM0
      squamous cell carcinoma. Laryngoscopy revealed severe supraglottic-pharyngeal
      stenosis with tethering of the epiglottis to the lateral pharyngeal walls.
      Optiflow HFNC was used to deliver 70 L/min of oxygen. After anesthetic induction,
      CO2 laser microlaryngoscopy was utilized to release scar tissue along the lateral
      epiglottic border, opening up the supraglottic airway sufficiently for
      endotracheal intubation and further laser resection. RESULTS: Airway management
      with Optiflow HFNC allowed initial endoscopic surgical access, partial stenotic
      release, and intubation. From anesthetic induction to intubation, the patient
      remained apneic for 26 minutes. The patient's stenosis was successfully
      addressed, and 10-month follow-up demonstrated stable patency of the airway.
      CONCLUSION: Optiflow is an important new tool in the management of severe
      supraglottic stenosis. It provides sufficient oxygenation to perform extended
      apneic surgery and improves endoscopic surgical access in a limited airway.

PMID- 28766978
TI  - Comparison of variability in breast density assessment by BI-RADS category
      according to the level of experience.
AB  - Background Only few studies have assessed variability in the results obtained by
      the readers with different experience levels in comparison with automated
      volumetric breast density measurements. Purpose To examine the variations in
      breast density assessment according to BI-RADS categories among readers with
      different experience levels and to compare it with the results of automated
      quantitative measurements. Material and Methods Density assignment was done for
      1000 screening mammograms by six readers with three different experience levels
      (breast-imaging experts, general radiologists, and students). Agreement level
      between the results obtained by the readers and the Volpara automated volumetric
      breast density measurements was assessed. The agreement analysis using two
      categories-non-dense and dense breast tissue-was also performed. Results Intra
      reader agreement for experts, general radiologists, and students were almost
      perfect or substantial (k = 0.74-0.95). The agreement between visual assessments
      of the breast-imaging experts and volumetric assessments by Volpara was
      substantial (k = 0.77). The agreement was moderate between the experts and
      general radiologists (k = 0.67) and slight between the students and Volpara (k =
      0.01). The agreement for the two category groups (nondense and dense) was almost
      perfect between the experts and Volpara (k = 0.83). The agreement was substantial
      between the experts and general radiologists (k = 0.78). Conclusion We observed
      similar high agreement levels between visual assessments of breast density
      performed by radiologists and the volumetric assessments. However, agreement
      levels were substantially lower for the untrained readers.

PMID- 28766979
TI  - Pancreatic neuroendocrine tumor: prediction of the tumor grade using CT findings
      and computerized texture analysis.
AB  - Background Pancreatic neuroendocrine tumors (PNET) include heterogeneous tumors
      with a variable degree of inherent biologic aggressiveness represented by the
      histopathologic grade. Although several studies investigated the computed
      tomography (CT) characteristics which can predict the histopathologic grade of
      PNET, accurate prediction of the PNET grade by CT examination alone is still
      limited. Purpose To investigate the important CT findings and CT texture
      variables for prediction of grade of PNET. Material and Methods Sixty-six
      patients with pathologically confirmed PNETs (grade 1 = 45, grades 2/3 = 21)
      underwent preoperative contrast-enhanced CT. Two reviewers determined the
      presence of predefined CT findings. CT texture was also analyzed on arterial and
      portal phase using both two-dimensional (2D) and three-dimensional (3D) analysis.
      Multivariate logistic regression analysis was performed in order to identify
      significant predictors for tumor grade. Results Among CT findings and CT texture
      variables, the significant predictors for grade 2/3 tumors were an ill-defined
      margin (odds ratio [OR] = 7.273), lower sphericity (OR = 0.409) on arterial 2D
      analysis, higher skewness (OR = 1.972) and lower sphericity (OR = 0.408) on
      arterial 3D analysis, lower kurtosis (OR = 0.436) and lower sphericity (OR =
      0.420) on portal 2D analysis, and a larger surface area (OR = 2.007) and lower
      sphericity (OR = 0.503) on portal 3D analysis ( P < 0.05). Diagnostic performance
      of texture analysis was superior to CT findings (AUC = 0.774 vs. 0.683).
      Conclusion CT is useful for predicting grade 2/3 PNET using not only the imaging
      findings including an ill-defined margin, but also the CT texture variables such
      as lower sphericity, higher skewness, and lower kurtosis.

PMID- 28766981
TI  - Image quality and radiation dose of CT venography with double dose reduction
      using model based iterative reconstruction: comparison with conventional CT
      venography using filtered back projection.
AB  - Background Computed tomography venography (CTV) at low kVp using model-based
      iterative reconstruction (MBIR) can enhance vascular enhancement with noise
      reduction. Purpose To evaluate image qualities and radiation doses of CTV at 80
      kVp using MBIR and a small iodine contrast media (CM) dose and to compare these
      with those of CTV performed using a conventional protocol. Material and Methods
      Sixty-five patients (mean age = 58.1 +/- 7.2 years) that underwent CTV for the
      evaluation of deep vein thrombosis (DVT) and varicose veins were enrolled in this
      study. Patients were divided into two groups: Group A (35 patients, 80 kVp, MBIR,
      automatic tube current modulation, CM = 270 mg/mL, 100 mL) and Group B (30
      patients, 100 kVp, filtered back projection [FBP], 120 fixed mA, CM = 370 mg/mL,
      120 mL). Objective and subjective image qualities of inferior vena cava (IVC),
      femoral vein (FV), and popliteal vein (PV) were assessed and radiation doses were
      recorded. Results Mean vascular enhancement in group A was significantly lower
      than in group B ( P < 0.01). Noise in group A was significantly lower than in
      group B except for PV and contrast-to-noise ratio were not significantly
      different in the two groups ( P > 0.05). In addition, radiation dose in group A
      was significantly lower than in group B ( P < 0.001). Subjective image quality
      comparison revealed group A was statistically inferior to group B except for
      subjective image noise. Conclusion CTV at 80 kVp using MBIR with small iodine
      contrast dose provided acceptable image quality at a lower radiation dose than
      conventional CTV using FBP.

PMID- 28766982
TI  - Featured Article: Serum [Met5]-enkephalin levels are reduced in multiple
      sclerosis and restored by low-dose naltrexone.
AB  - Low-dose naltrexone is a widely used off-label therapeutic prescribed for a
      variety of immune-related disorders. The mechanism underlying low-dose
      naltrexone's efficacy for fatigue, Crohn's disease, fibromyalgia, and multiple
      sclerosis is, in part, intermittent blockade of opioid receptors followed by
      upregulation of endogenous opioids. Short, intermittent blockade by naltrexone
      specifically blocks the opioid growth factor receptor resulting in biofeedback
      events that increase production of the endogenous opioid growth factor (OGF)
      (chemically termed [Met5]-enkephalin) facilitating interactions between opioid
      growth factor and opioid growth factor receptor that ultimately, result in
      inhibited cell proliferation. Preclinical studies have reported that enkephalin
      levels are deficient in animal models of experimental autoimmune
      encephalomyelitis, a mouse model of multiple sclerosis. Our hypothesis is that
      serum enkephalin levels are diminished in humans with multiple sclerosis and
      experimental autoimmune encephalomyelitis mice, and that change in serum opioid
      growth factor levels may serve as a reasonable candidate biomarker for the onset
      of experimental autoimmune encephalomyelitis and response to therapy. To address
      this, we designed a two-part study to measure endogenous opioids in multiple
      sclerosis patients, and to investigate the temporal pattern of decline in serum
      enkephalin concentrations in mice with chronic progressive experimental
      autoimmune encephalomyelitis and treated with low-dose naltrexone. For
      comparison, we investigated whether low-dose naltrexone exposure in normal mice
      also resulted in altered enkephalin levels. In both animal models, we monitored
      tactile and heat sensitivity, as well as differential white blood cell counts as
      indicators of inflammation. Serum [Met5]-enkephalin levels were lower in humans
      with multiple sclerosis relative to non-multiple sclerosis patients, and low-dose
      naltrexone restored their levels. In experimental autoimmune encephalomyelitis
      mice, [Met5]-enkephalin levels were depressed prior to the appearance of clinical
      disease, and were restored with low-dose naltrexone treatment. Low-dose
      naltrexone therapy had no effect on serum [Met5]-enkephalin or beta-endorphin in
      normal mice. Thus, [Met5]-enkephalin (i.e. opioid growth factor) may be a
      reasonable candidate biomarker for multiple sclerosis, and may signal new
      pathways for treatment of autoimmune disorders. Impact statement This report
      presents human and animal data identifying a novel biomarker for the onset and
      progression of multiple sclerosis (MS). Humans diagnosed with MS have reduced
      serum levels of OGF (i.e. [Met5]-enkephalin) relative to non-MS neurologic
      patients, and low-dose naltrexone (LDN) therapy restored their enkephalin levels.
      Serum OGF levels were reduced in mice immunized with MOG35-55 prior to any
      clinical behavioral sign of experimental autoimmune encephalomyelitis, and LDN
      therapy restored their serum OGF levels. beta-endorphin concentrations were not
      altered by LDN in humans or mice. Thus, blood levels of OGF may serve as a new,
      selective biomarker for the progression of MS, as well as response to therapy.

PMID- 28766983
TI  - LKB1-AMPK modulates nutrient-induced changes in the mode of division of
      intestinal epithelial crypt cells in mice.
AB  - Nutrient availability influences intestinal epithelial stem cell proliferation
      and tissue growth. Increases in food result in a greater number of epithelial
      cells, villi height and crypt depth. We investigated whether this nutrient-driven
      expansion of the tissue is the result of a change in the mode of intestinal
      epithelial stem cell division and if LKB1-AMPK signaling plays a role. We
      utilized in vivo and in vitro experiments to test this hypothesis. C57BL/6J mice
      were separated into four groups and fed varying amounts of chow for 18 h: (1) ad
      libitum, (2) 50% of their average daily intake (3) fasted or (4) fasted for 12 h
      and refed. Mice were sacrificed, intestinal sections excised and
      immunohistochemically processed to determine the mitotic spindle orientation.
      Epithelial organoids in vitro were treated with no (0 mM), low (5 mM) or high (20
      mM) amounts of glucose with or without an activator (Metformin) or inhibitor
      (Compound C) of LKB1-AMPK signaling. Cells were then processed to determine the
      mode of stem cell division. Fasted mice show a greater % of asymmetrically
      dividing cells compared with the other feeding groups. Organoids incubated with 0
      mM glucose resulted in a greater % of asymmetrically dividing cells compared with
      the low or high-glucose conditions. In addition, LKB1-AMPK activation attenuated
      the % of symmetric division normally seen in high-glucose conditions. In
      contrast, LKB1-AMPK inhibition attenuated the % of asymmetric division normally
      seen in no glucose conditions. These data suggest that nutrient availability
      dictates the mode of division and that LKB1-AMPK mediates this nutrient-driven
      effect on intestinal epithelial stem cell proliferation. Impact statement The
      underlying cell biology of changes in the polarity of mitotic spindles and its
      relevance to tissue growth is a new concept and, thus, these data provide novel
      findings to begin to explain how this process contributes to the regeneration and
      growth of tissues. We find that short-term changes in food intake in vivo or
      glucose availability in vitro dictate the mode of division of crypt cells. In
      addition, we find that LKB1-AMPK signaling modulates the glucose-induced changes
      in the mode of division in vitro. Identifying mechanisms involved in the mode of
      division may provide new targets to control tissue growth.

PMID- 28766985
TI  - Hemodynamic effects of low-dose atipamezole in isoflurane-anesthetized cats
      receiving an infusion of dexmedetomidine.
AB  - Objectives The objective of this study was to evaluate the cardiovascular effects
      of low-dose atipamezole administered intravenously to isoflurane-anesthetized
      cats receiving dexmedetomidine. We hypothesized that atipamezole would increase
      heart rate (HR) and reduce arterial blood pressure in isoflurane-anesthetized
      cats receiving dexmedetomidine. Methods Six healthy adult domestic shorthair cats
      were anesthetized with isoflurane and instrumented for direct arterial pressures
      and cardiac output (CO) measurements. The cats received a target-controlled
      infusion of dexmedetomidine (target plasma concentration 10 ng/ml) for 30 mins
      before administration of atipamezole. Two sequential doses of atipamezole (15 and
      30 MUg/kg IV) were administered at least 20 mins apart, during dexmedetomidine
      administration. The effects of dexmedetomidine and each dose of atipamezole on
      HR, mean arterial blood pressure (MAP), CO and systemic vascular resistance (SVR)
      were documented. Results Dexmedetomidine reduced the HR by 22%, increased MAP by
      78% (both P ?0.01), decreased CO by 48% and increased SVR by 58% (both P
      ?0.0003). Administration of atipamezole 15 and 30 MUg/kg intravenously increased
      HR by 8% ( P = 0.006) and 4% ( P = 0.1), respectively. MAP decreased by 39% and
      47%, respectively (both P ?0.004). Atipamezole 30 MUg/kg returned CO and SVR to
      baseline values. Conclusions and relevance Low doses of atipamezole (15 and 30
      MUg/kg) administered intravenously to anesthetized cats decreased arterial blood
      pressure with only marginal increases in HR. Atipamezole 30 MUg/kg restored CO
      and SVR to baseline values before dexmedetomidine administration.

PMID- 28766984
TI  - Long-term effect of parasympathetic or sympathetic denervation on intestinal
      epithelial cell proliferation and apoptosis.
AB  - Intestinal epithelial tissue is constantly regenerated as a means to maintain
      proper tissue function. Previous studies have demonstrated that denervation of
      the parasympathetic or sympathetic nervous system to the intestine alters this
      process. However, results are inconsistent between studies, showing both
      increases and decreases in proliferation after denervation of the parasympathetic
      or sympathetic. The effect appears to correlate with (1) the timing post
      denervation, (2) denervation-induced changes in food intake, (3) the denervation
      technique used, and (4) which intestinal segment is investigated. Thus, we
      proposed that parasympathetic or sympathetic denervation does not have an effect
      on intestinal epithelial regeneration when you (1) evaluate denervation after
      long-term denervation, (2) control for post-surgical changes in food intake, (3)
      use minimally invasive surgical techniques and (4) include a segmental analysis.
      To test this, adult male Sprague Dawley rats underwent parasympathetic
      denervation via subdiaphragmatic vagotomy, sympathetic denervation via
      celiacomesenteric ganglionectomy, a parasympathetic denervation sham surgery, or
      a sympathetic denervation sham surgery. Sham surgery ad libitum-fed groups and
      sham surgery pair-fed groups were used to control for surgically induced changes
      in food intake. Three weeks post-surgery, animals were sacrificed and tissue from
      the duodenum, jejunum, and ileum was excised and immunohistochemically processed
      to visualize indicators of proliferation (bromodeoxyuridine-positive cells) and
      apoptosis (caspase-3-positive cells). Results showed no differences between
      groups in proliferation, apoptosis, or total cell number in any intestinal
      segment. These results suggest that parasympathetic or sympathetic denervation
      does not have a significant long-term effect on intestinal epithelial turnover.
      Thus, intestinal epithelial regeneration is able to recover after autonomic
      nervous system injury. Impact statement This study investigates the long-term
      effect of autonomic denervation on intestinal epithelial cell turnover, as
      measured by proliferation, apoptosis, and total cell number. Although previous
      research has established that autonomic denervation can alter intestinal
      epithelial turnover under short-term conditions, here we establish for the first
      time that these changes do not persist long-term when you control for surgical
      induced changes in food intake and use targeted denervation procedures. These
      findings add to the base of knowledge on autonomic control of tissue turnover,
      highlight the ability of the intestinal epithelium to recover after autonomic
      injury and reveal possible implications of the use of ANS denervation for disease
      treatment in humans.

PMID- 28766986
TI  - The Untapped Potential of the Nurse Practitioner Workforce in Reducing Health
      Disparities.
AB  - The growing nurse practitioner (NP) workforce represents a significant supply of
      primary care providers, who if optimally utilized, are well-positioned to improve
      access to health care for racial and ethnic minorities. However, many barriers
      affect the optimal utilization of NPs in primary care delivery. These barriers
      may also prevent NPs from maximally contributing to efforts to reduce racial and
      ethnic health disparities. Our review of the empirical and health policy
      literature sought to elucidate factors that affect NPs' potential and ability to
      narrow or eliminate health disparities. We found that restrictive state scope of
      practice regulations, disparate reimbursement policies, lack of NP workforce
      diversity, and poor organizational structures in NP practices may limit NPs'
      contributions to current efforts to reduce disparities. Our results led to the
      development of the nurse practitioner health disparities model which identifies
      barriers to and opportunities for optimal use of NPs in reducing racial and
      ethnic disparities. State and federal policymakers and administrators in health
      care settings should take actions to remove legislative and organizational
      barriers to enable NPs to deliver high-quality care to racial and ethnic
      minorities. Researchers can use the nurse practitioner health disparities model
      to produce empirical evidence to reduce health disparities and improve population
      health.

PMID- 28766988
TI  - Correction to: Held and Hamada, Summary of the Bill Morgan Memorial Symposium -
      part 1: biology, epidemiology and radiation protection.

PMID- 28766987
TI  - Optical verification and in-vitro characterization of two commercially available
      acoustic bubble counters for cardiopulmonary bypass systems.
AB  - INTRODUCTION: Gaseous microemboli (GME) introduced during cardiac surgery are
      considered as a potential source of morbidity, which has driven the development
      of the first bubble counters. Two new generation bubble counters, introduced in
      the early 2000s, claim correct sizing and counting of GME. This in-vitro study
      aims to validate the accuracy of two bubble counters using monodisperse bubbles
      in a highly controlled setting at low GME concentrations. METHODS: Monodisperse
      GME with a radius of 43 um were produced in a microfluidic chip. Directly after
      their formation, they were injected one-by-one into the BCC200 and the EDAC
      sensors. GME size and count, measured with the bubble counters, were optically
      verified using high-speed imaging. RESULTS: During best-case scenarios or low GME
      concentrations of GME with a size of 43 um in radius in an in-vitro setup, the
      BCC200 overestimates GME size by a factor of 2 to 3 while the EDAC underestimates
      the average GME size by at least a factor of two. The BCC200 overestimates the
      GME concentration by approximately 20% while the EDAC overestimates the
      concentration by nearly one order of magnitude. Nevertheless, the calculated
      total GME volume is only over-predicted by a factor 2 since the EDAC
      underestimates the actual GME size. For the BCC200, the total GME volume was over
      predicted by 25 times due to the over-estimation of GME size. CONCLUSIONS: The
      measured errors in the absolute sizing/counting of GME do not imply that all
      results obtained using the bubble counters are insignificant or invalid. A
      relative change in bubble size or bubble concentration can accurately be
      measured. However, care must be taken in the interpretation of the results and
      their absolute values. Moreover, the devices cannot be used interchangeably when
      reporting GME activity. Nevertheless, both devices can be used to study the
      relative air removal characteristics of CPB components or for the quantitative
      monitoring of GME production during CPB interventions.

PMID- 28766989
TI  - Sixty years in psychiatry.
AB  - The author, who has spent over 60 years working in a variety of mental health
      settings, shares his personal perspective of the way psychiatry has evolved.
      Treatments, both physical and psychological, have come and some have been
      discarded. There have been radical changes in the delivery of care, from the 2000
      bed Victorian asylum to community care, and the on the whole beneficial impact of
      legislation such as mental health Acts and Acts dealing with suicide, abortion
      and sexual offences. His experience has warned him of the folly of overenthusiasm
      for some treatments - such as deep insulin for schizophrenia, psycho surgery, and
      even classical psychoanalysis which can become as addictive as any drug or a
      promise of salvation as convincing as a religion. On the other hand, a treatment
      involving passing electric shocks through the brain has stood the test of time
      and may be life saving for some patients.

PMID- 28766990
TI  - Involvement of NLRP10 in IL-1alpha induction of oral epithelial cells by
      periodontal pathogens.
AB  - This study investigated the pathogenesis of periodontitis and the role of
      nucleotide-binding oligomerization domain-like receptor protein 10 (NLRP10). The
      human oral epithelial cell line HOK-16B was infected with two periodontal
      pathogens, Tannerella forsythia and Fusobacterium nucleatum, at various MOIs. RT
      PCR and immunoblotting demonstrated that infection increased mRNA and protein
      expression of NLRP10, respectively. The siRNA-mediated NLRP10 knockdown
      significantly reduced IL-1alpha expression and secretion. Both bacteria induced
      phosphorylation of ERK, JNK and p38 MAP kinases in HOK-16B cells. NLRP10
      knockdown impaired ERK phosphorylation only. ERK inhibition significantly
      decreased the expression of T. forsythia- and F. nucleatum-induced IL-1alpha. Our
      data suggest that NLRP10 is involved in activating the ERK signalling pathway in
      HOK-16B cells infected with T. forsythia and F. nucleatum. This pathway likely
      augments the pro-inflammatory cytokine IL-1alpha levels, which may play a
      critical role in periodontitis.

PMID- 28766991
TI  - Mosquito Vectors of Avian Malaria in Mississippi: A First Look.
AB  - The vectors of avian malaria (Haemosporida) are an understudied component of
      wildlife disease ecology. Most studies of avian malaria have focused on the
      intermediate bird hosts. This bias leaves a significant gap in our knowledge and
      understanding of the insect hosts. This study investigates the diversity of
      malaria parasites carried by mosquitoes (Diptera, Culicidae) in the state of
      Mississippi. With the use of molecular techniques, haemosporidian infection rates
      were determined and parasites were identified. A total of 27,157 female
      mosquitoes representing 15 species were captured. Five of those species tested
      positive for malaria parasites with an overall infection rate of 4 per 1,000
      mosquitoes infected. Mosquitoes were shown to harbor Plasmodium and Haemoproteus
      ( Parahaemoproteus) parasites. A unique lineage of parasites was discovered in
      Anopheles mosquitoes, potentially representing a new genus of haemosporidian
      parasites, reinforcing the need to continue investigating this diverse group of
      parasites.

PMID- 28766993
TI  - Streamlined EDSS for use in multiple sclerosis clinical practice: Development and
      cross-sectional comparison to EDSS.
AB  - BACKGROUND: The Expanded Disability Status Scale (EDSS) is the standard measure
      of disability in multiple sclerosis clinical trials. The EDSS has limited
      application in the clinical setting due to required completion time and scoring
      complexity. Systematically recording an objective, simplified, less time
      intensive, and neurologist-derived disability score would be beneficial for
      patient care. OBJECTIVE: To develop and validate a streamlined version of the
      Expanded Disability Status Scale (sEDSS) for clinical monitoring. METHODS: The
      EDSS was modified by eliminating maneuvers with no impact on function,
      consolidating redundancies, and simplifying scoring. This sEDSS was refined and
      preliminarily validated using a pilot cohort of 102 patients. Subsequently, the
      sEDSS was retrospectively validated using 968 patients from the CombiRx trial. We
      evaluated correlation and agreement between each functional system as well as the
      overall sEDSS and EDSS. RESULTS: The sEDSS correlated strongly with the EDSS,
      both overall (Spearman's rho = 0.93) and for each functional system (Spearman's
      rho 0.65-0.97). Correlation was slightly lower for functional systems where
      scoring was modified for consolidation and simplification. CONCLUSION: The sEDSS
      had strong agreement and correlation with the existing EDSS and can provide a
      useful measure of disability in clinical practice.

PMID- 28766992
TI  - Lactobacillus fermentum 3872 as a potential tool for combatting Campylobacter
      jejuni infections.
AB  - Due to the global spread of multidrug resistant pathogenic bacteria, alternative
      approaches in combating infectious diseases are required. One such approach is
      the use of probiotics. Lactobacillus fermentum 3872 is a promising probiotic
      bacterium producing a range of antimicrobial compounds, such as hydrogen peroxide
      and lactic acid. In addition, previous studies involving genome sequencing and
      analysis of L. fermentum 3872 allowed the identification of a gene encoding a
      cell surface protein referred to as collagen binding protein (CBP) (not found in
      other strains of the species, according to the GenBank database), consisting of a
      C-terminal cell wall anchor domain (LPXT), multiple repeats of 'B domains' that
      form stalks presenting an "A domain" required for adhesion. In this study, we
      found that the CBP of L. fermentum 3872 binds to collagen I present on the
      surface of the epithelial cells lining the gastrointestinal tract. Moreover, we
      found that this host receptor is also used for attachment by the major
      gastrointestinal pathogen, Campylobacter jejuni. Furthermore, we identified an
      adhesin involved in such interaction and demonstrated that both L. fermentum 3872
      and its CBP can inhibit binding of this pathogen to collagen I. Combined with the
      observation that C. jejuni growth is affected in the acidic environment produced
      by L. fermentum 3872, the finding provides a good basis for further investigation
      of this strain as a potential tool for fighting Campylobacter infections.

PMID- 28766994
TI  - Past Pain Experience and Experimentally induced Pain Perception.
AB  - : Many intercurrent factors may be involved in the modulation of the pain message
      and its expression, such as the previous experience of pain built along the life.
      In this study, we aimed to determine whether susceptibility to experimentally
      induced pain is differentially influenced by the individual previous painful
      experience in subjects with schizophrenia (SC) major depression (MD), and
      controls (C). METHODS: The SC (30), MD (32) and C (30) groups participated in
      experimental pain tests (application of pressure and induction of ischemia) after
      a semi-structured interview to make an inventory of the previous painful
      experiences, and the evaluation of anxiety either with autonomic (heart rate,
      blood pressure) or psychological (Hospital Anxiety Depression scale HAD)
      measures, and catastrophism. RESULTS: The reported pain intensities, severities,
      duration, of the previous pain events, and the number of previous painful events
      were equivalent in the three groups, except for the number of painful events
      experimented before the last six months which was lower in the MD group.
      Experimental pain sensitivity was influenced by the diagnosis, the HAD scores or
      the number and intensities of previous lived painful events. CONCLUSION: The lack
      of a past experience of pain was comparable for the different groups, suggesting
      that psychiatric disorders do not affect the experience of pain associated with
      daily life or past events. For each subject, the reported previous experience of
      pain influences the present feeling of pain.

PMID- 28766995
TI  - Constitutive activity of the Arabidopsis MAP Kinase 3 confers resistance to
      Pseudomonas syringae and drives robust immune responses.
AB  - Mitogen Activated Protein Kinases (MAPKs) are known to be important mediators of
      plant responses to biotic and abiotic stresses. In a recent report, we enlarged
      the understanding of the Arabidopsis thaliana MPK3 functions showing that the
      expression of a constitutively active (CA) form of the protein led to auto-immune
      phenotypes. CA-MPK3 plants are dwarf and display defense responses that are
      characterized by the accumulation of salicylic acid and phytoalexins as well as
      by the upregulation of several defense genes. Consistently with these data, we
      present here results demonstrating that, compared with wild type controls, CA
      MPK3 plants are more resistant to the hemibiotrophic pathogen Pseudomonas
      syringae DC3000. Based on our previous work, we also discuss the mechanisms of
      robust plant immunity controlled by sustained MPK3 activity, focusing especially
      on the roles of disease resistance proteins.

PMID- 28766997
TI  - Palliative Medicine: A Medical Student's Perspective.

PMID- 28766996
TI  - Temporally and Spatially Regulated Expression of the Linker Histone H1fx During
      Mouse Development.
AB  - The linker histone H1fx is the least characterized member of the H1 family. To
      investigate the developmental changes of H1fx, we performed an
      immunohistochemical analysis of its expression pattern from embryos to adult
      mice. We found that H1fx was highly expressed during gastrulation, and was
      positive in all embryonic germ layers between E8.5 and E10.5, which mostly
      overlapped with the expression of the proliferation marker Ki-67. Neural and
      mesenchyme tissues strongly expressed H1fx at E10.5. H1fx expression began to be
      restricted at around E12.5. Western blot analysis of brain tissues demonstrated
      that the total expression level of H1fx gradually decreased with time from E12.5
      to adulthood, whereas H1f0 was increased over this period. In adult mice, H1fx
      was restrictively expressed at the hypothalamus, subventricular zone, subgranular
      zone, medulla of the adrenal grand, islets of Langerhans, and myenteric plexus.
      Taken together, these data suggest that H1fx is preferentially expressed in
      immature embryonic cells and plays some roles in cells with neural properties.

PMID- 28766998
TI  - Linguistic Analysis as a Method for Assessing Symptoms After Sexual Trauma Among
      Female Adolescent Psychiatric Inpatients.
AB  - Using a sample of female psychiatric inpatient adolescents, the current study
      aimed to extend this literature to an adolescent sample for the first time by
      examining if linguistic markers and their subcategories (cognitive process words,
      pronoun use, and somatosensory detail) in a trauma account are related to trauma
      symptomology and recovery during inpatient care. Results indicated that greater
      use of body words and fewer insight words were related to increased trauma
      symptoms at admission. In addition, use of fewer cognitive process words at
      admission predicted greater symptom change at discharge, extending previous
      research findings to an adolescent sample. Findings suggest that linguistic
      analysis may be an important component of adolescent trauma symptom assessment
      and treatment monitoring.

PMID- 28767000
TI  - Pyoderma gangrenosum associated with Crohn's disease in a Malawian teenage boy:
      case report and review of literature.

PMID- 28766999
TI  - Cross-cultural adaptation of the Child and Adolescent Symptom Inventory-5 (CASI
      5) for use in central and south-western Uganda: the CHAKA project.
AB  - Our study was to examine the applicability of translating and culturally adapting
      the Child and Adolescent Symptom Inventory-5 (CASI-5) for use in Uganda. This
      process followed guidelines recommended by the International Test Commission. A
      number of the CASI-5 concepts needed to be revised to capture the idioms for
      emotional, behavioural disorders and individual functioning among children and
      adolescents in Uganda. Our experience is that before introduction into another
      culture, psychological assessment instruments should undergo an adaptation
      process such as as the one used.

PMID- 28767001
TI  - Victims' Retrospective Explanations of Sibling Sexual Violence.
AB  - While sibling sexual abuse may be the most common form of sexual violence within
      the family, relatively few studies have been conducted on this topic. The current
      study addresses this gap in the literature through analyses of thematic
      categories in narratives gathered from an online survey of sibling sexual
      violence. Survivors were asked to report why they believed their siblings had
      become sexually abusive toward them. Participants believed that their abusers had
      learned to be abusive due to their own victimization or exposure to pornography,
      were abusive to establish dominance over them, or had some undisclosed mental
      illness. While the study does not claim to test these explanations or include
      abusers' own narratives, it offers insight as to how sibling sexual violence
      survivors make sense of their experiences and assign blame to abusers and their
      families. It also offers insights into future inquiries about sibling sexual
      abuse.

PMID- 28767003
TI  - The Right to Live with Dignity and the Right to Die with Dignity.

PMID- 28767002
TI  - Employment status five years after a randomised controlled trial comparing
      multidisciplinary and brief intervention in employees on sick leave due to low
      back pain.
AB  - AIMS: To evaluate differences in employment status, during a five-year follow-up
      period in patients on sick leave due to low back pain who had participated in a
      trial comparing a brief and a multidisciplinary intervention. METHODS: From 2004
      to 2008, 535 patients were referred to the Spine Centre at the Regional Hospital
      in Silkeborg if they had been on sick leave for 3-16 weeks due to low back pain.
      All patients underwent a clinical examination by a rehabilitation physician and a
      physiotherapist, and were randomised to either the brief intervention or the
      multidisciplinary intervention. The outcome was employment status from
      randomisation to five years of follow-up and was measured by the mean number of
      weeks in four different groups of employment status (sequence analysis) and a
      fraction of the number of weeks working (work participation score) that were
      accumulated over the years. RESULTS: A total of 231 patients were randomised to
      the brief intervention and 233 patients to the multidisciplinary intervention. No
      statistically significant differences in the mean weeks spent within the
      different employment statuses were found between the two intervention groups.
      After five years of follow-up, participants in the multidisciplinary intervention
      had a 19% higher risk of not having a work participation score above 75% compared
      to participants in the brief intervention. CONCLUSIONS: After five years of
      follow-up no differences in employment status were found between participants in
      the brief and the multidisciplinary intervention.

PMID- 28767004
TI  - Do anti-neutrophil cytoplasmic antibodies play a role in systemic lupus
      erythematosus (SLE) patients? Analysis of the University College Hospital SLE
      cohort.

PMID- 28767005
TI  - Intensive Case Management for Severe Mental Illness.

PMID- 28767006
TI  - Potentially traumatic events as predictors of disability pension: A 10-year
      follow-up study in Norway.
AB  - AIMS: Are potentially traumatic events associated with subsequent disability
      pension? Traumatic exposure and post-traumatic stress disorder (PTSD) may
      represent a disabling state with both personal and professional consequences for
      the affected individual. Despite this, there is a scarcity of research studying
      the effects of traumatic exposure on disability pension. This study examined the
      differences in risk for disability pension among unexposed, exposed to trauma and
      PTSD cases. METHODS: An ambidirectional Norwegian cohort study, consisting of
      1238 individuals aged 18-66 years who were at risk of disability pension, were
      interviewed using the Composite International Diagnostic Interview, and linked
      with registry data on disability pension. Registry follow-up in the Norwegian
      Insurance Database lasted ten years following interview in 2000-01. The risk of
      disability pension after traumatic exposure, divided into accidental and
      premeditated, was assessed by Cox proportional hazards regression analysis.
      RESULTS: In 10 years, 9.5% of the cohort had been granted disability pension.
      Overall exposure to traumatic events did not alter the risk of disability
      pension. However, among women, exposure to premeditated traumas did increase the
      risk (HR 2.96 (95% CI 1.54-5.68)), and was an independent risk factor. Fulfilling
      criteria for PTSD caseness further increased the risk (HR 4.69 (95% CI 1.78
      12.40)). There was no increased risk found between traumatic exposure and
      disability pension for men. CONCLUSIONS: Exposure to trauma, particularly
      premeditated trauma, seems to be an independent risk factor for disability
      pension in women.

PMID- 28767007
TI  - "I am not a friend to men": Embodiment and desire in Magnus Hirschfeld's
      Transvestites case studies.
AB  - This article reads sexological case studies of the fin-de siecle that contain
      accounts of trans women's lives in the period. It argues that these sources
      contradict the diagnostic criteria that doctors determine as the factors that
      define trans feminine identity in the period: desire for men, social isolation,
      and tortured bodily dissatisfaction. Chief among these contradictions is the
      prevalence of the expression of trans women's desire for women and easy
      participation in women's social and kinship networks. Therefore, this article
      considers these narratives to be a crucial and overlooked resource for
      considering the breadth of lesbian identity and sociality in the late nineteenth
      and early twentieth century.

PMID- 28767008
TI  - The Edible Mushroom Pleurotus djamor Produces Metabolites with Lethal Activity
      Against the Parasitic Nematode Haemonchus contortus.
AB  - Pleurotus djamor is an edible mushroom that has medicinal properties. This study
      aimed to assess the in vitro activity of P. djamor extracts and fractions against
      Haemonchus contortus eggs and exsheathed infective larvae (L3). Crude
      hydroalcoholic extracts were obtained by maceration and fractions were obtained
      through chromatography. Metabolite identity was determined using gas
      chromatography/mass spectrometry (GC-MS) analysis. The results showed that P.
      djamor extracts had no significant activity against eggs at the concentrations
      used. However, the extract showed 98.7% and 77% larval mortality 72 h
      postconfrontation at 320 and at 160 mg/mL, respectively. The chromatography
      analysis resulted in 23 fractions that were eventually grouped into three
      fractions (E1, E2, and E3). These fractions showed the following egg hatching
      inhibition percentages: E1 = 100, E2 = 38.7, and E3 = 5.5 at 10 mg/mL
      concentration 72 h postexposure. Likewise, larval mortality percentages after
      this period were 90.6, 100, and 0.44 at 40 mg/mL (P < .05), respectively. The GC
      MS showed five major compounds in E1 fraction, including four fatty acids: (i)
      pentadecanoic, (ii) hexadecanoic, (iii) octadecadienoic, (iv) octadecanoic acid,
      and one terpene identified as beta-sitosterol. We concluded that the edible
      mushroom P. djamor possesses nematicidal metabolites, which could be used as an
      alternative anthelmintic treatment.

PMID- 28767009
TI  - A no-man's-land of sex: Reading Stephen Gordon and "her" critics.
AB  - One of the most read novels of lesbian, transgender, and queer criticism,
      Radclyffe Hall's novel The Well of Loneliness (1928) has given rise to numerous
      and contradictory interpretations of the protagonist Stephen Gordon's complex
      relationship to her body. Some have argued that she is a historically specific
      example of female masculinity, others that she is a lesbian who wishes she were
      more feminine, and others still that she is a prototypical transsexual character.
      Focusing on the exemplary essays by Jack Halberstam, Teresa de Lauretis, and Jay
      Prosser, I argue that the coexistence of mutually exclusive interpretations of
      Stephen Gordon's relationship to her femaleness suggests that the novel is, in
      fact, a demand to readers to unmoor identity from sex and to recognize what I
      call "sexual indeterminacy." Lesbian, transgender, and queer theory's tendency to
      elide the literariness of literary objects and their reliance on critique as the
      primary mode of reading and argumentation have made it impossible for critics to
      see that the novel is explicitly about what cannot be settled.

PMID- 28767010
TI  - Social Support of Adolescent Survivors of Child Sexual Abuse and Sexual
      Revictimization in Turkey.
AB  - Sexual revictimization refers to having a history of child sexual abuse and an
      experience of being assaulted again in adolescence or adulthood. This descriptive
      study examined perceived social support of nonvictim adolescents and adolescents
      who had survived single sexual abuse and sexual revictimization. Participants
      were 210 adolescent girls, all aged between 15 and 18, selected by a convenience
      sampling method; 70 had survived sexual revictimization, 70 had survived single
      sexual abuse, and 70 were nonvictims. The Perceived Social Support Scale was
      administered, and a one-way ANOVA was conducted for data analysis. Perceived
      social support from the community was lower in the sexual revictimization group
      than in the single sexual abuse and comparison groups. Family social support did
      not differ between the sexual revictimization and single sexual abuse groups but
      was lower in both than in the comparison group. These results indicate that
      victims of sexual revictimization need social support, and both sexual
      revictimization and single sexual abuse victims need familial support.

PMID- 28767011
TI  - Personality Disorders and Health: Lessons Learned and Future Directions.

PMID- 28767012
TI  - Role of Borderline Personality Disorder in the Treatment of Military Sexual
      Trauma-related Posttraumatic Stress Disorder with Cognitive Processing Therapy.
AB  - Cognitive Processing Therapy (CPT) is an effective evidence-based treatment for
      many, but not all, veterans with posttraumatic stress disorder (PTSD).
      Understanding the factors that contribute to poorer response to CPT is important
      for providing the best care to veterans diagnosed with PTSD. Researchers
      investigating the effectiveness of CPT for individuals with comorbid personality
      symptoms have found that borderline personality disorder (BPD) characteristics do
      not negatively affect treatment outcome; however, participants in those studies
      were not diagnosed with BPD. The current pilot study investigated the effect of a
      BPD diagnosis on CPT dropout and outcomes. Data were compiled from a larger
      randomized clinical trial. Twenty-seven female veterans with military sexual
      trauma-related PTSD received CPT. Dropout was evaluated by treatment completion
      and number of sessions attended. Treatment outcome was assessed by the Clinician
      Administered PTSD Scale (CAPS) and the PTSD Checklist (PCL). No significant
      differences were observed between veterans with and without BPD comorbidity for
      number of treatment sessions attended, and there was not a significant
      relationship between comorbidity status and treatment completion. A hierarchical
      linear modeling approach was used with BPD entered as a level 2 predictor of
      outcome. In our sample, veterans with BPD had higher PTSD symptom severity on the
      CAPS at baseline compared to veterans without BPD comorbidity. CPT was effective
      in reducing PTSD symptoms; however, BPD diagnosis did not influence treatment
      response over time on the CAPS or PCL. Our results provide initial support for
      the use of CPT in female veterans with MST-related PTSD and comorbid BPD.

PMID- 28767013
TI  - Narcissistic Personality Disorder in Clinical Health Psychology Practice: Case
      Studies of Comorbid Psychological Distress and Life-Limiting Illness.
AB  - Narcissistic Personality Disorder (NPD) is characterized by a persistent pattern
      of grandiosity, fantasies of unlimited power or importance, and the need for
      admiration or special treatment. Individuals with NPD may experience significant
      psychological distress related to interpersonal conflict and functional
      impairment. Research suggests core features of the disorder are associated with
      poor prognosis in therapy, including slow progress to behavioral change,
      premature patient-initiated termination, and negative therapeutic alliance. The
      current manuscript will explore challenges of working with NPD within the context
      of life-limiting illness for two psychotherapy patients seen in a behavioral
      health clinic at a large academic health science center. The ways in which their
      personality disorder affected their illness-experience shared significant overlap
      characterized by resistance to psychotherapeutic change, inconsistent adherence
      to medical recommendations, and volatile relationships with providers. In this
      manuscript we will (1) explore the ways in which aspects of narcissistic
      personality disorder impacted the patients' physical health, emotional well
      being, and healthcare utilization; (2) describe psychotherapeutic methods that
      may be useful for optimizing psychosocial, behavioral, and physical well-being in
      individuals with co-morbid NPD and life-limiting disease; and (3) review
      conceptualizations of NPD from the DSM-5 alternative model for assessing
      personality function via trait domains.

PMID- 28767014
TI  - HIV Risk, Substance Use, and Personality Characteristics among Adults with
      History of Serious Mental Illness.
AB  - The present study examined the relationship between characteristics associated
      with personality disorders, substance use, and HIV risk among adults with a
      history of serious mental illness. Participants included 103 adults with
      antisocial or borderline personality disorder, serious mental illness, and recent
      HIV risk behavior. The sample was predominately male (64%), diverse (42% African
      American and 13% Hispanic), and homeless/marginally housed (76%). In order to
      examine the relationship between personality characteristics and risk we
      constructed a risk index comprising key symptoms of antisocial and borderline
      personality disorders, namely; impulsivity, affective instability, and disregard
      for safety of self/others. Contrary to our primary hypotheses, risk index scores
      did not predict HIV risk behavior and substance abuse did not mediate this risk.
      Exploratory analyses did reveal that women engaged in significantly more risk
      behaviors than their male counterparts and that risk scores were a significant
      predictor of total sex acts for women but not men. In addition, increased
      emotional dysregulation was a significant predictor of condomless sex acts for
      women but not men. Finally, recent alcohol use and increased impulsivity was
      associated with more condomless oral sex for men and women. These results suggest
      the relationship among serious mental illness, personality disorder, substance
      abuse, and gender is complex and merits further study.

PMID- 28767015
TI  - Dependency Traits, Relationship Power, and Health Risks in Women Receiving
      Sexually-Transmitted Infection Clinic Services.
AB  - In prior research, having traits consistent with a personality disorder has been
      shown to be related to substance use and high-risk sexual activity; however, few
      studies have examined relationships between dependency traits and health
      jeopardizing behaviors. Individuals with traits consistent with dependent
      personality disorder may be more likely to be in a primary relationship
      characterized by unhealthy conditions, including physical abuse from a partner,
      low assertiveness in sexual situations, and partner infidelity. In addition,
      dependency traits may be associated with unhealthy coping (e.g., through
      substance use). To examine associations between dependent personality traits and
      these types of health-related behaviors, 198 women seeking sexually transmitted
      infection clinic services completed a computer-assisted assessment of dependent
      personality traits, substance use, unhealthy conditions in primary relationships,
      perceived sexual and relationship power, and sexual risk related to condom use.
      Dependency trait scores were correlated with the use of cocaine, heroin, and
      methamphetamine. Participants high in dependency traits reported low perceived
      power within their relationships and less say in sexual behaviors, including
      condom use. In a series of multivariate analyses, dependency traits significantly
      predicted having been hit by a partner, staying with a partner after he cheated,
      having sex because of threats, and fear of asking a partner to use a condom.
      Dependency traits were also associated with lower past condom use and lower
      future condom use intentions. Results suggest that dependent personality traits
      may place women at higher risk for physical abuse and harmful health behaviors.

PMID- 28767016
TI  - Personality Disorders and Psychological Functioning Among Latina Women with
      Eating Disorders.
AB  - Little is known about personality disorders (PD) and comorbidities among Latinas
      with eating disorders (ED). The dysregulation and chronicity of PDs can
      complicate and augment the symptomatology of EDs. This set of analyses provides a
      preliminary examination of PD and psychopathology in a sample of Latina women
      with ED. Participants (N = 34) were administered the Structured Clinical
      Interview for the Diagnostic and Statistical Manual, Eating Disorders
      Examination, and Millon Clinical Multiaxial Inventory-III to assess personality
      pathology, and questionnaires (Beck Depression Inventory-II and Brief Symptom
      Inventory) to assess psychological functioning. Results indicated the most common
      clinically significant trait in the sample was depressive personality (50% of the
      sample had a score of 75 or higher on this trait). For Bulimia Nervosa (BN) and
      Binge Eating Disorder (BED), avoidant (41%) and depressive (65%) personalities,
      respectively, were the most common clinically significant traits. Anxiety
      disorders were the most common psychiatric diagnoses, and 52.9% of the sample
      reported both clinically significant PD traits and other major psychopathology.
      There were no significant differences between the BED and BN groups on prevalence
      of PD traits and psychopathology. This pilot study highlights the need for
      further examination of PD and psychopathology in Latinas with ED. Unlike previous
      research with White women, we found no differences on PD and psychopathology
      between BED and BN, and the most prevalent PDs among Latinas were different than
      White women. Personality and psychological functioning should be assessed in all
      patients with ED, with ongoing research focused on identifying patterns in
      understudied groups such as Latinas, a practice that may improve treatment for
      this underserved population.

PMID- 28767017
TI  - Association Between Borderline Personality Features and Temporal Summation of
      Second Pain: A Cross-Sectional Study.
AB  - Individuals with greater borderline personality features may be vulnerable to
      chronic pain. Because pain is an unpleasant sensory and emotional experience,
      affect dysregulation as the core personality feature may be linked to pain
      hypersensitivity. Studies have found that greater borderline features are
      associated with increased intensity in clinical and experimental pain, and that
      depression mediates this increase. The current study further examined the
      association between borderline features and heat pain sensitivity, the
      contribution of affect dysregulation and the other borderline personality factors
      (identity problems, negative relationships, self-harming/impulsivity) to the
      association, and depression as a mediator. Additionally, we examined whether
      blunted sympathetic responses mediate the association between borderline features
      and temporal summation of second pain (TSSP). Thermal pain threshold, thermal
      TSSP and aftersensations pain were assessed in 79 healthy individuals with
      varying degrees of borderline features. TSSP is a proxy measure for central
      sensitization and refers to the gradual increase in pain to repeated nociceptive
      stimuli. A regression analysis showed that greater borderline features predicted
      greater TSSP (beta = .22, p = .050, R2 = .05). Borderline features were unrelated
      to pain threshold and TSSP decay. A stepwise regression showed greater TSSP in
      individuals with greater borderline features was accounted for by the negative
      relationships factor rather than the affect dysregulation factor. The results of
      mediational analyses showed depression and blunted sympathetic skin conductance
      responses mediated the positive association between TSSP and borderline features.

PMID- 28767018
TI  - Poor Sleep and Its Relation to Impulsivity in Patients with Antisocial or
      Borderline Personality Disorders.
AB  - Studies investigating sleep and personality disorders consistently demonstrate a
      relation between personality disorders characterized by behavioral disinhibition
      and/or emotional dysregulation (traditionally termed cluster B personality
      disorders) and poor sleep. This finding is in line with previous studies
      associating insomnia with impulsive behavior, since this is a core characteristic
      of both antisocial and borderline personality disorder. The current study
      investigates a group (n = 112) of forensic psychiatric inpatients with antisocial
      or borderline personality disorder or traits thereof. Subjective sleep
      characteristics and impulsivity were assessed with the Pittsburgh Sleep Quality
      Index, the Sleep Diagnosis List, and the Barratt Impulsiveness Scale,
      respectively. More than half of the patients (53.6%) report poor sleep quality
      and 22.3% appears to suffer from severe chronic insomnia. Both poor sleep quality
      and chronic insomnia are significantly associated with self-reported impulsivity,
      in particular with attentional impulsiveness. This association was not
      significantly influenced by comorbid disorders. Actively treating sleep problems
      in these patients may not only improve sleep quality, mental health, and physical
      well-being, but may also have impact on impulsivity-related health risks by
      increasing self-control.

PMID- 28767019
TI  - Delineating the Interplay of Personality Disorders and Health.

PMID- 28767021
TI  - The limits of stability in patients with unilateral vestibulopathy.
AB  - OBJECTIVE: To characterize the stability limits and region in patients with
      unilateral vestibulopathy according to the side of the lesion and determine if
      that imposes any bias. To analyze if the stability limits and region depend on
      the functional deficit as evaluated in the sensory organization test. METHODS:
      Forty patients with chronic dizziness and without any vertigo spell for least 6
      months prior to testing. In all of them, a unilateral vestibulopathy was
      diagnosed clinically and at vestibular testing. A computerized dynamic
      posturography system was used to test for the ability of patients and controls to
      displace their center of pressure (COP) to the corresponding LOS. The area was
      calculated and compared to other data from vestibular tests. RESULTS: The area of
      stability among patients shows a reduction to 35-62% of the expected total. That
      reduction was not found to be dependent on age. CONCLUSION: There is a symmetric
      reduction in the limits of stability (LOS) in patients with unilateral
      vestibulopathy who suffer chronic instability. None of the areas measured were
      correlated with the composite score of the sensory organization test and, as
      such, must be considered as an adjunct measure to characterize the postural
      limitations in those patients.

PMID- 28767020
TI  - Personality and its Relation to Mental and Psychosocial Health in Emerging Adult
      Sexual Minority Men: The P18 Cohort Study.
AB  - Personality disorder and personality pathology encompass a dimension of
      psychological dysfunction known to severely impact multiple domains of
      functioning. However, there is a notable dearth of research regarding both the
      pervasiveness and correlates of personality pathology among young sexual minority
      males who themselves experience heightened mental health burdens. Using the self
      report version of the Standardized Assessment of Personality-Abbreviated Scale we
      tested associations between distinct personality characteristics with
      sociodemographic and psychosocial factors as well as mental health states in a
      sample of 528 young (aged 21-25 years) sexual minority men. In multivariate
      analysis, personality traits varied significantly by race/ethnicity. Personality
      traits were also positively associated with psychosocial states, specifically,
      internalized anti-homosexual bias, level of connection with the gay community,
      and male body dissatisfaction, as well as mental health in the form of recent
      depressive and anxious symptomatology. These findings support the complex synergy
      which exists between personality characteristics, psychosocial conditions, and
      mental health burdens present among sexual minority men and support the need for
      an all-encompassing approach to both the study and care of this population that
      addresses the influences of both internal and external factors on well-being.

PMID- 28767022
TI  - Failure patterns and prognostic factors of patients with primary mucosal melanoma
      of the nasal cavity and paranasal sinuses.
AB  - OBJECTIVES: To analyse the failure patterns and prognostic factors influencing
      survival in patients with primary mucosal melanoma of the nasal cavity and
      paranasal sinuses. MATERIALS AND METHODS: Fifty-one patients were analysed
      retrospectively. Forty-eight, 33, 10, and 13 patients underwent surgery,
      radiotherapy, chemotherapy, and immunotherapy, respectively. Failure events,
      including local recurrence, regional relapse, distant metastases, and death, were
      examined. RESULTS: During follow-up (median: 59.0 months), 36 patients
      experienced failure after treatment, including local (n = 17), regional (n = 8),
      and distant organ (n = 23) metastases. The median failure times for local,
      regional, and distant metastases were 13.0, 14.0, and 8.0 months, respectively.
      The median survival times from local, regional, and distant failure to death were
      10.5, 8.0, and 4.0 months, respectively. The 5-year overall survival rates of
      patients with and without distant organ metastases were 14.4% and 72.6%,
      respectively (p < .001). Multivariate analyses showed that radiotherapy increased
      local recurrence-free and regional relapse-free survival. Patients with stage IV
      tumours had reduced distant metastasis-free and overall survival compared to
      patients with stage I-III tumours. CONCLUSIONS: Distant metastasis was mainly
      owing to failure. Radiotherapy and the disease stage were prognostic factors for
      survival.

PMID- 28767023
TI  - [Cerebral vasculitis, a diagnostic labyrinth].
AB  - - A diagnosis of cerebral vasculitis is frequently considered in patients with
      new or progressive neurological symptoms for which there is no other explanation.
      A clinician considering a diagnosis of cerebral vasculitis should be well aware
      of alternative diagnoses, since these are generally more common.- Several
      consecutive examinations are required for diagnosing cerebral vasculitis, because
      there is no diagnostic procedure that is highly sensitive as well as highly
      specific.- The added value of the different procedures may depend on the type of
      blood vessels involved.- Standard MRI examinations are sensitive but not
      specific.- Special MRI techniques now make it also possible to make images of the
      vessel wall itself.- Catheter angiography remains important, especially when non
      invasive angiographic techniques do not reveal any abnormalities.- Brain biopsy
      can provide proof of cerebral vasculitis and also serves to exclude mimicking
      conditions.

PMID- 28767024
TI  - [A woman with lower back pain].
AB  - A 88-year old woman presented with severe pain in the lower back which radiated
      to her left leg. She was diagnosed with a sacral insufficiency fracture. Sacral
      insufficiency fractures are a cause of lower back pain in the elderly population
      that is frequently overlooked because the symptoms and signs are not specific.

PMID- 28767025
TI  - [Appropriate care in the last phase of life].
AB  - OBJECTIVE: To identify the types of care that patients and relatives perceive as
      appropriate or inappropriate in the last phase of life. DESIGN: Questionnaire
      survey. METHOD: By means of an internet questionnaire with open questions, we
      asked patients and relatives about their experiences of care in the last phase of
      life and if they found it appropriate or inappropriate, and why. We recruited via
      e-mails, Twitter, Facebook, newsletters and links on homepages of patient
      organisations. Members of a Dutch large organisation for older people (Unie KBO)
      received the questionnaire on paper. RESULTS: Forty-five patients and 547
      relatives described received one or more cases. We found 429 cases of appropriate
      care and 309 different cases of inappropriate care. We identified five common
      dimensions of appropriate and inappropriate care, i.e., supportive care,
      treatment decisions, location of care, following the patient's wishes and
      communication. In the cases of appropriate care, all five dimensions were
      regularly mentioned; supportive care being most-frequently mentioned. In cases of
      inappropriate care, the dimensions treatment decisions, supportive care and
      communication were most often mentioned. Descriptions of appropriate care more
      frequently concerned patients with cancer, and descriptions of inappropriate care
      more frequently concerned patients with other somatic conditions or psychiatric
      conditions. Nurses or carers and general practitioners were more often mentioned
      in descriptions of appropriate care, and medical specialists more often mentioned
      in descriptions of inappropriate care. CONCLUSION: Appropriate care appears to be
      a wide-ranging term covering supportive care, treatment decisions, communication,
      following the patient's wishes, and the location where care is provided.
      Inappropriate treatment decisions and communication problems are the main threats
      to appropriate care in the last phase of life.

PMID- 28767026
TI  - [The gestational age label].
AB  - Recent follow-up data on babies born at > 24 weeks' gestation in the Netherlands
      has shown encouraging results; these outcomes reflect policy in national
      guidelines to limit treatment in babies born at < 24 weeks' gestation. The use of
      gestational age as a cut-off point for active treatment in extremely premature
      infants is, however, scientifically and ethically questionable. As an alternative
      we should consider a tailor-made approach by well-informed, ethically trained
      doctors who feel comfortable with complex decision-making, irrespective of the
      gestational age label.

PMID- 28767027
TI  - [Early discharge possible in acute upper gastrointestinal bleeding; new study
      results require adaptation of Dutch guideline].
AB  - Acute upper gastrointestinal bleeding is still an important emergency situation
      with an incidence of 48-62 per 100,000 adults per year in the Netherlands. An
      international multicentre prospective study evaluated different risk scoring
      systems for patients presenting with upper gastrointestinal bleeding. The authors
      showed that patients with a Glasgow Blatchford score of 0 or 1 could be safely
      discharged without endoscopy. Thirty-day all-cause mortality in this group was
      0.4%. In the current Dutch guideline, there is no clear advice on management of
      low-risk patients. The new guideline is expected in 2017 and should include this
      clear advice of discharging low-risk patients (Glasgow Blatchford score <= 1). It
      can therefore be concluded that with optimal selection about 20% of all patients
      presenting to the emergency room with acute upper gastrointestinal bleeding can
      be discharged the same day without intervention.

PMID- 28767028
TI  - [The Dutch College of General Practitioners practice guideline 'Suspicious skin
      lesions'].
AB  - - The Dutch College of General Practitioners practice guideline 'Suspicious skin
      lesions' provides recommendations for diagnosis, treatment and referral for the
      most common premalignant and malignant skin disorders.- The practice guideline
      includes a flowchart which starts by looking at the colour and surface of the
      skin lesion to direct the general practitioner to the most likely diagnosis.- In
      case of strong suspicion of squamous cell carcinoma, keratoacanthoma or melanoma
      and in case of basal cell carcinoma or Bowen's disease with high-risk
      characteristics, the general practitioner will refer the patient to a
      dermatologist.- The general practitioner will take into account the
      histopathological diagnosis in determining treatment and referral policy in case
      of other suspicious skin lesions. It will be obtained by means of punch biopsy or
      - in the case of naevi - diagnostic excision.- In case of suspicious skin
      lesions, the general practitioner will inspect the whole skin.- General
      practitioner and patient should determine a treatment plan together in case of
      actinic keratosis, histopathologically diagnosed basal cell carcinoma, and
      Bowen's disease. To this end, the practice guideline includes information on
      treatment options for general practitioners and dermatologists.

PMID- 28767029
TI  - Recurrent Impulse Control Disorder Associated with Rasagiline Treatment of
      Parkinson's Disease.

PMID- 28767030
TI  - Shifting Trend of Transient Ischemic Attack Admission and Prognosis in Canada.
AB  - BACKGROUND: Stroke is often preceded by transient symptoms. Although global
      stroke rates have been shown to be declining, previous studies have reported
      inconsistent temporal trends of transient ischemic attacks (TIA). The objective
      of the current study is to report the temporal trends of TIA admissions and
      outcomes in Canada over the last 11 years. METHODS: We conducted a complete
      population cohort study using a national administrative database to study the
      temporal trend of age- and sex-adjusted TIA admission rates in Canada from 2003
      to 2013. We also determined the rates of TIA and stroke diagnoses in the
      emergency department in the province of Ontario during the same period. We used
      multivariable analyses to study discharge location after acute hospitalization as
      well as 90-day stroke and/or TIA readmission rates. RESULTS: Of 425,799
      admissions to an acute care hospital for all stroke and TIA, 71,443 (16.8%) were
      TIA. The age- and sex-standardized rates of TIA admission decreased significantly
      during the study period from 30.0 to 20.6 per 100,000 (p<0.0001). In Ontario,
      decreasing TIA admissions is mirrored by decreasing rates of TIA directly
      discharged from the emergency department (55.1 to 46.8 per 100,000, p = 0.002).
      The odds of 90-day readmission rates for stroke or TIA are also decreasing
      (adjusted odds ratio, 0.97; 95% confidence interval, 0.96-0.99). CONCLUSIONS: We
      show that TIA admission rates have declined in the past 11 years in Canada,
      reflecting improved vascular risk reduction and stroke care. Future studies to
      confirm our findings on improved stroke or TIA recurrence rates are necessary.

PMID- 28767031
TI  - Microsurgical Vascular Manipulation in Aneurysm Surgery and Delayed Ischemic
      Injury.
AB  - BACKGROUND: The role of aggressive surgical manipulation with clot evacuation,
      arachnoid dissection, and papaverine-guided adventitial dissection of large
      vessels during ruptured aneurysm surgery in reducing vasospasm is controversial.
      Here we describe a single-institution experience in aneurysm surgery outcomes
      with and without aggressive surgery. METHODS: We performed retrospective analysis
      of all patients >18 years of age with subarachnoid hemorrhage (SAH) from anterior
      circulation aneurysms between 2008 and 2013 at the University of New Mexico
      Hospital. Vasospasm was characterized on days 3 through 14 after SAH based on:
      (1) angiography, (2) vasospasm requiring angiographic intervention, (3)
      development of delayed ischemic neurologic deficit (DIND), and (4) radiological
      appearance of new strokes. RESULTS: Of 159 patients, 114 (71.6%) had "aggressive"
      and 45 (28.3%) had standard microsurgery. More than 60% of patients presented
      with a Hunt and Hess score of >=3 and a Fisher grade (FG) of 4. Compared with
      standard surgery, there was a statistically significant decrease in the incidence
      of DIND in patients undergoing aggressive surgery (18.4% vs 37.8%, p=0.01).
      Moreover, there was a reduction in the number of new strokes by 30% in the
      aggressive surgery group with moderate or higher degrees of vasospasm (46.0% vs
      76.5%, p=0.06). In the same group with FG 4 SAH, however, this difference was
      more than 50% (30% vs 64.7%, p=0.02). CONCLUSIONS: We conclude that aggressive
      surgical manipulation during aneurysm surgery results in lower incidence of DIND
      and new strokes. This effect is most pronounced in patients with FG 4 SAH.

PMID- 28767032
TI  - Subacute Supranuclear Palsy in anti-Hu Paraneoplastic Encephalitis.

PMID- 28767033
TI  - Bruns' Nystagmus and Positive Head Impulse Tests in Platybasia.

PMID- 28767034
TI  - Diagnostic Accuracy of Transient Ischemic Attack from Physician Claims.
AB  - BACKGROUND: Hospitalization data underestimate the occurrence of transient
      ischemic attack (TIA). As TIA is frequently diagnosed in primary care,
      methodologies for the accurate ascertainment of a TIA from physician claims data
      are required for surveillance and health systems planning in this population. The
      present study evaluated the diagnostic accuracy of multiple algorithms for TIA
      from a longitudinal population-based physician billing database. METHODS:
      Population-based administrative data from the province of British Columbia were
      used to identify the base population (1992-2007; N=102,492). Using discharge
      records for hospital admissions for acute ischemic stroke with a recent (<90
      days) TIA as the reference standard, we performed receiver-operating
      characteristic analyses to calculate sensitivity, specificity, positive and
      negative predictive values and overall accuracy, and to compare area under the
      curve for each physician billing algorithm. To evaluate the impact of different
      case definitions on population-based TIA burden, we also estimated the annual TIA
      occurrence associated with each algorithm. RESULTS: Physician billing algorithms
      showed low to moderate sensitivity, with the algorithm for two consecutive
      physician visits within 90 days showing the highest sensitivity at 37.7% (CI
      95%=37.4-38.1). All algorithms demonstrated high specificity and moderate to high
      overall accuracy, resulting in low positive predictive values (<=5%), low
      discriminability (0.53-0.57) and high false positive rates (1 - specificity).
      Population-based estimates of TIA occurrence were comparable to prior studies and
      declined over time. CONCLUSIONS: Physician billing data have insufficient
      sensitivity to identify TIAs but may be used in combination with hospital
      discharge data to improve the accuracy of estimating the population-based
      occurrence of TIAs.

PMID- 28767035
TI  - Neuropsychological Outcome in Perinatal Stroke Associated With Epileptiform
      Discharges in Sleep.
AB  - BACKGROUND: Patients with arterial perinatal stroke often suffer long-term motor
      sequelae, difficulties in language, social development, and behaviour as well as
      epilepsy. Despite homogeneous lesions, long-term behavioural and cognitive
      outcomes are variable and unpredictable. Sleep-related epileptic encephalopathies
      can occur after early brain injury and are associated with global developmental
      delays. We hypothesized that sleep-potentiated epileptiform abnormalities are
      associated with worse developmental outcomes after perinatal stroke. METHODS:
      Participants were identified from a population-based cohort (Alberta Perinatal
      Stroke Project). Inclusion criteria were magnetic resonance imaging-confirmed
      arterial perinatal stroke, age 4 to 18 years, electroencephalogram (EEG)
      including sleep, and comprehensive neuropsychological evaluation. Sleep-related
      EEG abnormalities were categorized by an epileptologist blinded to the cognitive
      outcome. Associations between EEG classification and neuropsychological outcomes
      were explored (t tests, Bonferroni correction for multiple comparisons). RESULTS:
      Of 128 potentially eligible participants, 34 (53% female) had complete EEG (mean
      age, 8.1 years; range, 0.2-16.4) and neuropsychology testing (mean age, 9.8
      years; range 4.4-16.7). Twelve (35%) were classified as having electrical status
      epilepticus in sleep. Patients with abnormal EEGs were more likely to have
      statistically worse scores when corrected for multiple comparisons, in receptive
      language (median, 1st percentile; IQR 1-7th percentile; p<0.05), and
      externalizing behaviours (median, 82nd percentile; IQR, 79-97th percentile;
      p<0.05). CONCLUSIONS: Developmental outcome in language and behaviour in children
      with arterial perinatal stroke is associated with electrical status epilepticus
      in sleep. Increased screening with sleep EEG is suggested, whereas further
      studies are necessary to determine if treatment of EEG abnormalities can improve
      outcome.

PMID- 28767036
TI  - Six-Month Response to Delamanid Treatment in MDR TB Patients.
AB  - Delamanid, recently available for the treatment of multidrug-resistant
      tuberculosis (MDR TB), has had limited use outside clinical trials. We present
      the early treatment results for 53 patients from 7 countries who received a
      delamanid-containing treatment for MDR TB. Results show good tolerability and
      treatment response at 6 months.

PMID- 28767037
TI  - Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom
      resolution.
AB  - Coactivator complexes SAGA and NuA4 stimulate transcription by post
      translationally modifying chromatin. Both complexes contain the Tra1 subunit, a
      highly conserved 3744-residue protein from the Phosphoinositide 3-Kinase-related
      kinase (PIKK) family and a direct target for multiple sequence-specific
      activators. We present the Cryo-EM structure of Saccharomyces cerevsisae Tra1 to
      3.7 A resolution, revealing an extensive network of alpha-helical solenoids
      organized into a diamond ring conformation and is strikingly reminiscent of DNA
      PKcs, suggesting a direct role for Tra1 in DNA repair. The structure was fitted
      into an existing SAGA EM reconstruction and reveals limited contact surfaces to
      Tra1, hence it does not act as a molecular scaffold within SAGA. Mutations that
      affect activator targeting are distributed across the Tra1 structure, but also
      cluster within the N-terminal Finger region, indicating the presence of an
      activator interaction site. The structure of Tra1 is a key milestone in
      deciphering the mechanism of multiple coactivator complexes.

PMID- 28767040
TI  - Hydrogen-peroxide-modified egg albumen for transparent and flexible resistive
      switching memory.
AB  - Egg albumen is modified by hydrogen peroxide with concentrations of 5%, 10%, 15%
      and 30% at room temperature. Compared with devices without modification, a memory
      cell of Ag/10% H2O2-egg albumen/indium tin oxide exhibits obviously enhanced
      resistive switching memory behavior with a resistance ratio of 104, self-healing
      switching endurance for 900 cycles and a prolonged retention time for a 104 s @
      200 mV reading voltage after being bent 103 times. The breakage of massive
      protein chains occurs followed by the recombination of new protein chain networks
      due to the oxidation of amidogen and the synthesis of disulfide during the
      hydrogen peroxide modifying egg albumen. Ions such as Fe3+, Na+, K+, which are
      surrounded by protein chains, are exposed to the outside of protein chains to
      generate a series of traps during the egg albumen degeneration process. According
      to the fitting results of the double logarithm I-V curves and the current-sensing
      atomic force microscopy (CS-AFM) images of the ON and OFF states, the charge
      transfer from one trap center to its neighboring trap center is responsible for
      the resistive switching memory phenomena. The results of our work indicate that
      hydrogen- peroxide-modified egg albumen could open up a new avenue of biomaterial
      application in nanoelectronic systems.

PMID- 28767038
TI  - Microtubule-dependent ribosome localization in C. elegans neurons.
AB  - Subcellular localization of ribosomes defines the location and capacity for
      protein synthesis. Methods for in vivo visualizing ribosomes in multicellular
      organisms are desirable in mechanistic investigations of the cell biology of
      ribosome dynamics. Here, we developed an approach using split GFP for tissue
      specific visualization of ribosomes in Caenorhabditis elegans. Labeled ribosomes
      are detected as fluorescent puncta in the axons and synaptic terminals of
      specific neuron types, correlating with ribosome distribution at the
      ultrastructural level. We found that axonal ribosomes change localization during
      neuronal development and after axonal injury. By examining mutants affecting
      axonal trafficking and performing a forward genetic screen, we showed that the
      microtubule cytoskeleton and the JIP3 protein UNC-16 exert distinct effects on
      localization of axonal and somatic ribosomes. Our data demonstrate the utility of
      tissue-specific visualization of ribosomes in vivo, and provide insight into the
      mechanisms of active regulation of ribosome localization in neurons.

PMID- 28767039
TI  - FXR1 regulates transcription and is required for growth of human cancer cells
      with TP53/FXR2 homozygous deletion.
AB  - Tumor suppressor p53 prevents cell transformation by inducing apoptosis and other
      responses. Homozygous TP53 deletion occurs in various types of human cancers for
      which no therapeutic strategies have yet been reported. TCGA database analysis
      shows that the TP53 homozygous deletion locus mostly exhibits co-deletion of the
      neighboring gene FXR2, which belongs to the Fragile X gene family. Here, we
      demonstrate that inhibition of the remaining family member FXR1 selectively
      blocks cell proliferation in human cancer cells containing homozygous deletion of
      both TP53 and FXR2 in a collateral lethality manner. Mechanistically, in addition
      to its RNA-binding function, FXR1 recruits transcription factor STAT1 or STAT3 to
      gene promoters at the chromatin interface and regulates transcription thus, at
      least partially, mediating cell proliferation. Our study anticipates that
      inhibition of FXR1 is a potential therapeutic approach to targeting human cancers
      harboring TP53 homozygous deletion.

PMID- 28767042
TI  - Greatly improved dispersibility of Pt quantum dots in hematite nanoarray and
      enhanced photoelectrochemical performance.
AB  - The anchoring of platinum quantum dots (Pt QDs) on the surface of hematite (alpha
      Fe2O3) nanorods is regarded as an efficient way to promote photoelectrochemical
      activity. To further improve the performance of the Pt-hematite material system,
      the size and location of the Pt QDs is a key factor to be considered. In this
      work, an alpha-Fe2O3 nanorod array film was grown on a transparent conductive FTO
      substrate by a facile hydrothermal method. Pt QDs with a diameter of ~2 nm were
      uniformly deposited on the surface of the alpha-Fe2O3 nanorod. The dispersibility
      of the Pt QDs was greatly improved by regulating the surface wettability of the
      alpha-Fe2O3 thin film. The dependence of surface wettability on the micro-/nano
      structure of the alpha-Fe2O3 array was revealed. Due to the structure regulation
      of the alpha-Fe2O3 nanoarray and the greatly improved dispersibility of the Pt
      QDs, the photocurrent of the 2.7 wt% Pt QD anchored alpha-Fe2O3 nanorod array was
      ten times higher than that of the pure alpha-Fe2O3 nanorod array. This work
      points to an efficient approach for dispersing the QDs in a nanoarray thin film
      by adjusting its micro-/nano-structure and surface wettability.

PMID- 28767041
TI  - Multifunctional halloysite nanotubes for targeted delivery and controlled release
      of doxorubicin in-vitro and in-vivo studies.
AB  - The current state of cancer therapy encourages researchers to develop novel
      efficient nanocarriers. Halloysite nanotubes (HNTs) are good nanocarrier
      candidates due to their unique nanoscale (40-80 nm in diamter and 200-500 nm in
      length) and hollow lumen, as well as good biocompatibility and low cost. In our
      study, we prepared a type of folate-mediated targeting and redox-triggered
      anticancer drug delivery system, so that Doxorubicin (DOX) can be specifically
      transported to tumor sites due to the over-expressed folate-receptors on the
      surface of cancer cells. Furthermore, it can then be released by the reductive
      agent glutathione (GSH) in cancer cells where the content of GSH is nearly 103
      fold higher than in the extracellular matrix. A series of methods have
      demonstrated that per-thiol-beta-cyclodextrin (beta-CD-(SH)7) was successfully
      combined with HNTs via a redox-responsive disulfide bond, and folic acid
      polyethylene glycol-adamantane (FA-PEG-Ad) was immobilized on the HNTs through
      the strong complexation between beta-CD/Ad. In vitro studies indicated that the
      release rate of DOX raised sharply in dithiothreitol (DTT) reducing environment
      and the amount of released DOX reached 70% in 10 mM DTT within the first 10 h,
      while only 40% of DOX was released in phosphate buffer solution (PBS) even after
      79 h. Furthermore, the targeted HNTs could be specifically endocytosed by over
      expressed folate-receptor cancer cells and significantly accelerate the apoptosis
      of cancer cells compared to non-targeted HNTs. In vivo studies further verified
      that the targeted HNTs had the best therapeutic efficacy and no obvious side
      effects for tumor-bearing nude mice, while free DOX showed damaging effects on
      normal tissues. In summary, this novel nanocarrier system shows excellent
      potential for targeted delivery and controlled release of anticancer drugs and
      provides a potential platform for tumor therapy.

PMID- 28767043
TI  - Glutathione responsive micelles incorporated with semiconducting polymer dots and
      doxorubicin for cancer photothermal-chemotherapy.
AB  - Nanoplatform integrated with photothermal therapy (PTT) and chemotherapy has been
      recognized a promising agent for enhancing cancer therapeutic outcomes, but still
      suffer from less controllability for optimizing their synergistic effects. We
      fabricated glutathione (GSH) responsive micelles incorporated with semiconducting
      polymer dots and doxorubicin (referred as SPDOX NPs) for combining PTT with
      chemotherapy to enhance cancer therapeutic efficiency. These micelles, with
      excellent water dispersibility, comprises of three distinct functional
      components: (1) the monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S
      C16), which forms the micelles, can render hydrophobic substances water-soluble
      and improve the colloidal stability; (2) disulfide linkages can be cleaved in a
      reductive environment for tumor specific drug release due to the high GSH
      concentrations of tumor micro-environment; (3) PCPDTBT dots and anti-cancer drug
      DOX that are loaded inside the hydrophobic core of the micelle can be applied to
      simultaneously perform PTT and chemotherapy to achieve significantly enhanced
      tumor killing efficiency both in vitro and in vivo. In summary, our studies
      demonstrated that our SPDOX NPs with simultaneous photothermal-chemotherapy
      functions could be a promising platform for a tumor specific responsive drug
      delivery system.

PMID- 28767044
TI  - Improved sensing characteristics of methane over ZnO nano sheets upon implanting
      defects and foreign atoms substitution.
AB  - Thanks to the growing interests of metal oxide sensors in environmental and
      industrial uses, this study presents the sensing mechanism of methane gas (CH4)
      on recently synthesized two-dimensional form of ZnO, ZnO nano sheets (ZnO-NS).
      The adsorption energy of CH4 on pristine ZnO-NS, calculated by means of van der
      Waals corrected first-principles calculations, is found to be insufficient
      restricting its application as an efficient nano sensor. However, the creation of
      (O/Zn) vacancies and the substitution of foreign dopants into ZnO-NS considerably
      intensify the binding energy of CH4. Through a comprehensive energetic analysis,
      it is observed that among all the substituents, boron (B), sulphur (S) and
      gallium (Ga) improves the binding of CH4 to 2.75, 6.1 and 7.5 times respectively
      than its values on pristine ZnO-NS. In addition to the CH4 binding energies
      falling ideally between physisorption and chemisorption range, a prominent
      variation in the electronic properties before and after CH4 exposure indicates
      the promise of substituted Zn-NS as a useful nano sensors.

PMID- 28767045
TI  - Acetic acid and pepsin result in high yield, high purity and low macrophage
      response collagen for biomedical applications.
AB  - Collagen based devices are frequently associated with foreign body response.
      Although several pre- (e.g. species, state of animal, tissue) and post- (e.g.
      cross-linking, scaffold architecture) extraction method factors have a profound
      effect on foreign body response, little is known about which and how during the
      extraction process factors mediate foreign body response. In this study, we
      assessed the influence of acetic acid and hydrochloric acid and the utilisation
      or not of pepsin or salt precipitation during collagen extraction on the yield,
      purity, free amines, denaturation temperature, resistance to collagenase
      degradation and macrophage response. Acetic acid/pepsin extracted collagen
      exhibited the highest yield, purity and free amine content and the lowest
      denaturation temperature. No differences in resistance to collagenase digestion
      were detected between the groups. Although all treatments exhibited similar
      macrophage morphology comprised of round cells (M1 phenotype), elongated cells
      (M2 phenotype) and cell aggregates (foreign body response), significantly more
      elongated cells were observed on HC films. Although no differences in metabolic
      activity were observed between the groups, the DNA concentration was
      significantly lower for the hydrochloric acid treatments. Further, cytokine
      analysis revealed that hydrochloric acid treatments induced significantly higher
      IL-1beta and TNF-alpha release with respect to acetic acid treatments. Salt
      precipitation did not influence the parameters assessed. Collectively, these data
      suggest that during the collagen extraction process variables should also be
      monitored as, evidently, they affect the physicochemical and biological
      properties of collagen preparations.

PMID- 28767046
TI  - Efficient methodology to correlate structural with optical properties of GaAs
      nanowires based on scanning electron microscopy.
AB  - Twin boundaries and boundaries between zincblende (ZB) and wurtzite (WZ) segments
      of GaAs-related nanowires (NWs) form intrinsic heterointerfaces with essential
      consequences for the application of such nanomaterials in optoelectronic devices.
      We show that for GaAs and GaAs/(Al, Ga)As core/shell NWs, crystal twinning along
      the NW axis can be imaged with a spatial resolution of 10 nm using secondary
      electrons in a scanning electron microscope (SEM). Changes of the crystal
      structure from the ZB to the WZ phase have been investigated by electron
      backscatter diffraction. In addition to these methods, we employ spectrally and
      spatially resolved cathodoluminescence measurements in the same SEM to study the
      correlation between the structural and optical properties in single NWs. Two
      GaAs/AlAs/GaAs core/shell/shell NWs differing significantly in the crystal
      structure along their axis have been investigated combining these three
      techniques in order to demonstrate the strength of the employed methodology. Our
      experiments show that based on commonly available SEM methods, an overview of the
      structural properties along an entire NW and their impact on the spectral and
      spatial luminescence distribution can be efficiently obtained providing a quick
      feedback for the optimization of growth conditions.

PMID- 28767047
TI  - Effects of Cu doping on the electronic structure and magnetic properties of
      MnCo2O4 nanostructures.
AB  - Reported here are the results and their analysis from our detailed investigations
      of the effects of Cu doping ([Formula: see text]) on the electronic structure and
      magnetic properties of the spinel [Formula: see text]O4. A detailed comparison is
      given for the [Formula: see text] and [Formula: see text] cases for both the bulk
      like samples and nanoparticles. The electronic structure determined from x-ray
      photoelectron spectroscopy and Rietveld analysis of x-ray diffraction patterns
      shows the structure to be: ([Formula: see text])A [Formula: see text] [Formula:
      see text] [Formula: see text]]B [Formula: see text] i.e. [Formula: see text]
      substitutes for [Formula: see text] on the octahedral B-sites. For the bulk
      samples, the ferrimagnetic [Formula: see text] K for [Formula: see text] is
      lowered to [Formula: see text] K for the [Formula: see text] sample, this
      decrease being due to the effect of Cu doping. For the nanosize [Formula: see
      text] ([Formula: see text]) sample, the lower [Formula: see text] K ([Formula:
      see text] K) is observed using [Formula: see text] analysis, this lowering being
      due to finite size effects. For [Formula: see text], fits of dc paramagnetic
      susceptibility data of [Formula: see text] versus T in nanosize samples to the
      Neel expression are used to determine the exchange interactions between the A and
      B sites with exchange constants: [Formula: see text] K (4.1 K), [Formula: see
      text] K (16.3 K) and [Formula: see text] K (13.8 K) for [Formula: see text]. The
      temperature dependence of ac susceptibilities [Formula: see text] and [Formula:
      see text] at different frequencies shows that in bulk samples of [Formula: see
      text] and [Formula: see text], the transition at T C is the normal second order
      transition. But for the nanosize [Formula: see text] and 0.2 samples, analysis of
      the ac susceptibilities shows that the ferrimagnetic transition at T C is
      followed by a re-entrant spin-glass transition at lower temperatures [Formula:
      see text] K (138 K) for [Formula: see text] ([Formula: see text]). Analysis of
      the ac susceptibilities, [Formula: see text] and [Formula: see text], versus T
      data is done in terms of two scaling laws: (i) Vogel-Fulcher law [Formula: see
      text] [Formula: see text]; and (ii) power law of critical slowing-down [Formula:
      see text]. These fits confirm the existence of glassy behavior below T SG with
      the parameters [Formula: see text] (8.91), [Formula: see text] (9.6  * 
      10[Formula: see text]) and [Formula: see text] K (~138 K) for the samples
      [Formula: see text] (0.2), with similar results obtained for other samples. The
      linear behavior of the peak maximum in [Formula: see text] versus [Formula: see
      text] (AT-line) further supports the existence of glassy states in nanosize
      samples. For [Formula: see text], the temperature and composition dependence of
      the hysteresis loop parameters are investigated; all the samples with x  ?  0.1
      have the coercivity H C and remanence [Formula: see text]. Since the results
      reported here in these nanostructures are significantly different from those in
      bulk [Formula: see text] [Formula: see text], further investigations of their
      magnetic structures using neutron diffraction are warranted.

PMID- 28767048
TI  - Rapid heat treatment for anatase conversion of titania nanotube orthopedic
      surfaces.
AB  - The amorphous to anatase transformation of anodized nanotubular titania surfaces
      has been studied by x-ray diffraction and transmission electron microscopy (TEM).
      A more rapid heat treatment for conversion of amorphous to crystalline anatase
      favorable for orthopedic implant applications was demonstrated. Nanotube titania
      surfaces were fabricated by electrochemical anodization of Ti6Al4V in an
      electrolyte containing 0.2 wt% NH4F, 60% ethylene glycol and 40% deionized water.
      The resulting surfaces were systematically heat treated in air with isochronal
      and isothermal experiments to study the temperature and time dependent
      transformation respectively. Energy dispersive spectroscopy shows that the
      anatase phase transformation of TiO2 in the as-anodized amorphous nanotube layer
      can be achieved in as little as 5 min at 350  degrees C in contrast to reports of
      higher temperature and much longer time. Crystallinity analysis at different
      temperatures and times yield transformation rate coefficients and activation
      energy for crystalline anatase coalescence. TEM confirms the (101) TiO2 presence
      within the nanotubes. These results confirm that for applications where amorphous
      titania nanotube surfaces are converted to crystalline anatase, a 5 min
      production flow-through heating process could be used instead of a 3 h batch
      process, reducing time, cost, and complexity.

PMID- 28767049
TI  - Learning dynamic models for open loop predictive control of soft robotic
      manipulators.
AB  - The soft capabilities of biological appendages like the arms of Octopus vulgaris
      and elephants' trunks have inspired roboticists to develop their robotic
      equivalents. Although there have been considerable efforts to replicate their
      morphology and behavior patterns, we are still lagging behind in replicating the
      dexterity and efficiency of these biological systems. This is mostly due to the
      lack of development and application of dynamic controllers on these robots which
      could exploit the morphological properties that a soft-bodied manipulator
      possesses. The complexity of these high-dimensional nonlinear systems has
      deterred the application of traditional model-based approaches. This paper
      provides a machine learning-based approach for the development of dynamic models
      for a soft robotic manipulator and a trajectory optimization method for
      predictive control of the manipulator in task space. To the best of our knowledge
      this is the first demonstration of a learned dynamic model and a derived task
      space controller for a soft robotic manipulator. The validation of the controller
      is carried out on an octopus-inspired soft manipulator simulation derived from a
      piecewise constant strain approximation and then experimentally on a
      pneumatically actuated soft manipulator. The results indicate that such an
      approach is promising for developing fast and accurate dynamic models for soft
      robotic manipulators while being applicable on a wide range of soft manipulators.

PMID- 28767050
TI  - Filamentous Fungal Human Pathogens from Food Emphasising Aspergillus, Fusarium
      and Mucor.
AB  - Disease caused by filamentous fungal human pathogens (FFHP) is increasing. These
      organisms cause severe mycoses in immunosuppressed individuals, such as those:
      (a) with AIDS; (b) having undergone transplantation; and/or (c) undergoing
      chemotherapy. Immunocompetent people can become infected. Some FFHP are isolated
      from foods which may be fomites. However, the information concerning particular
      species on specific food is large, dispersed and difficult to obtain. Reports of
      filamentous fungi from food/crops and causing human disease are frequently only
      available in the literature of food mycology/plant pathology and medical
      mycology, respectively: it is seldom cross-referenced. Aspergillus contains some
      species with strains that are the most dangerous FFHP, with Aspergillus fumigatus
      causing the most serious diseases. Fusarium and Mucor also contain species of
      high importance and approximately 15 other genera are involved. A checklist and
      database of FFHP species isolated from food is presented herein with emphasis on
      Aspergillus, Fusarium and Mucor in summary tables to increase awareness of the
      connection between food and FFHP. Metadata on all FFHP is provided in a large
      supplementary table for updating and revision when necessary. Previous names of
      fungi have been revised to reflect current valid usage whenever appropriate. The
      information will form a foundation for future research and taxonomic revisions in
      the field. The paper will be highly useful for medical practitioners, food
      mycologists, fungal taxonomists, patients, regulators and food producers
      interested in reducing infectious diseases and producing high quality food.

PMID- 28767051
TI  - Sensitivity and Frequency-Response Improvement of a Thermal Convection-Based
      Accelerometer.
AB  - This paper presents a thermal convection-based sensor fabricated using simple
      microelectromechanical systems (MEMS)-based processes. This sensor can be applied
      to both acceleration and inclination measurements without modifying the
      structure. Because the operating mechanism of the accelerometer is the thermal
      convection of a gas medium, a simple model is proposed and developed in which the
      performance of the thermal convection-based accelerometer is closely associated
      with the Grashof number, Gr and the Prandtl number, Pr. This paper discusses the
      experiments that were performed by varying several parameters such as the heating
      power, cavity size, gas media, and air pressure. The experimental results
      demonstrate that an increase in the heating power, pressure, and cavity size
      leads to an increase in the accelerometer sensitivity. However, an increase in
      the pressure and/or cavity size results in a decrease in the frequency bandwidth.
      This paper also discusses the fact that a working-gas medium with a large thermal
      diffusivity and small kinematic viscosity can widen the frequency bandwidth and
      increase the sensitivity, respectively.

PMID- 28767052
TI  - Strepchazolins A and B: Two New Alkaloids from a Marine Streptomyces chartreusis
      NA02069.
AB  - Two new alkaloids, strepchazolins A (1) and B (2), together with a previously
      reported compound, streptazolin (3), were isolated from a marine actinomycete,
      Streptomyces chartreusis NA02069, collected in the Coast of Hainan Island, China.
      The structures of new compounds were determined by extensive NMR, mass
      spectroscopic and X-ray crystallographic analysis, as well as modified Mosher's
      method. Compound 1 showed weak anti-Bacillus subtilis activity with the MIC value
      of 64.0 MUM, and weak inhibitory activity against acetylcholinesterase (AChE) in
      vitro with IC50 value of 50.6 MUM, while its diastereoisomer, Compound 2, is
      almost inactive.

PMID- 28767053
TI  - Charge Transfer Effect on Raman and Surface Enhanced Raman Spectroscopy of
      Furfural Molecules.
AB  - The detection of furfural in transformer oil through surface enhanced Raman
      spectroscopy (SERS) is one of the most promising online monitoring techniques in
      the process of transformer aging. In this work, the Raman of individual furfural
      molecules and SERS of furfural-Mx (M = Ag, Au, Cu) complexes are investigated
      through density functional theory (DFT). In the Raman spectrum of individual
      furfural molecules, the vibration mode of each Raman peak is figured out, and the
      deviation from experimental data is analyzed by surface charge distribution. In
      the SERS of furfural-Mx complexes, the influence of atom number and species on
      SERS chemical enhancement factors (EFs) are studied, and are further analyzed by
      charge transfer effect. Our studies strengthen the understanding of charge
      transfer effect in the SERS of furfural molecules, which is important in the
      online monitoring of the transformer aging process through SERS.

PMID- 28767054
TI  - Acceleration Mechanisms of Skin Wound Healing by Autologous Micrograft in Mice.
AB  - A micrograft technique, which minces tissue into micro-fragments >50 MUm, has
      been recently developed. However, its pathophysiological mechanisms in wound
      healing are unclear yet. We thus performed a wound healing study using normal
      mice. A humanized mouse model of a skin wound with a splint was used. After total
      skin excision, tissue micro-fragments obtained by the Rigenera protocol were
      infused onto the wounds. In the cell tracing study, GFP-expressing green mice and
      SCID mice were used. Collagen stains including Picrosirius red (PSR) and
      immunohistological stains for alpha-smooth muscle actin (alphaSMA), CD31,
      transforming growth factor-beta1 (TGF-beta1) and neutrophils were evaluated for
      granulation tissue development. GFP-positive cells remained in granulation tissue
      seven days after infusion, but vanished after 13 days. Following the infusion of
      the tissue micrograft solution onto the wound, TGF-beta1 expression was
      transiently upregulated in granulation tissue in the early phase. Subsequently,
      alphaSMA-expressing myofibroblasts increased in number in thickened granulation
      tissue with acceleration of neovascularization and collagen matrix maturation. On
      such granulation tissue, regenerative epithelial healing progressed, resulting in
      wound area reduction. Alternative alteration after the micrograft may have
      increased alphaSMA-expressing myofibroblasts in granulation tissue, which may act
      on collagen accumulation, neovascularization and wound contraction. All of these
      changes are favorable for epithelial regeneration on wound.

PMID- 28767055
TI  - Modeling the Colchicum autumnale Tubulin and a Comparison of Its Interaction with
      Colchicine to Human Tubulin.
AB  - Tubulin is the target for many small-molecule natural compounds, which alter
      microtubules dynamics, and lead to cell cycle arrest and apoptosis. One of these
      compounds is colchicine, a plant alkaloid produced by Colchicum autumnale. While
      C. autumnale produces a potent cytotoxin, colchicine, and expresses its target
      protein, it is immune to colchicine's cytotoxic action and the mechanism of this
      resistance is hitherto unknown. In the present paper, the molecular mechanisms
      responsible for colchicine resistance in C. autumnale are investigated and
      compared to human tubulin. To this end, homology models for C. autumnale alpha
      beta tubulin heterodimer are created and molecular dynamics (MD) simulations
      together with molecular mechanics Poisson-Boltzmann calculations (MM/PBSA) are
      performed to determine colchicine's binding affinity for tubulin. Using our
      molecular approach, it is shown that the colchicine-binding site in C. autumnale
      tubulin contains a small number of amino acid substitutions compared to human
      tubulin. However, these substitutions induce significant reduction in the binding
      affinity for tubulin, and subsequently fewer conformational changes in its
      structure result. It is suggested that such small conformational changes are
      insufficient to profoundly disrupt microtubule dynamics, which explains the high
      resistance to colchicine by C. autumnale.

PMID- 28767058
TI  - Synthesis of Distinct Iron Oxide Nanomaterial Shapes Using Lyotropic Liquid
      Crystal Solvents.
AB  - A room temperature reduction-hydrolysis of Fe(III) precursors such as FeCl3 or
      Fe(acac)3 in various lyotropic liquid crystal phases (lamellar, hexagonal
      columnar, or micellar) formed by a range of ionic or neutral surfactants in H2O
      is shown to be an effective and mild approach for the preparation of iron oxide
      (IO) nanomaterials with several morphologies (shapes and dimensions), such as
      extended thin nanosheets with lateral dimensions of several hundred nanometers as
      well as smaller nanoflakes and nanodiscs in the tens of nanometers size regime.
      We will discuss the role of the used surfactants and lyotropic liquid crystal
      phases as well as the shape and size differences depending upon when and how the
      resulting nanomaterials were isolated from the reaction mixture. The presented
      synthetic methodology using lyotropic liquid crystal solvents should be widely
      applicable to several other transition metal oxides for which the described
      reduction-hydrolysis reaction sequence is a suitable pathway to obtain nanoscale
      particles.

PMID- 28767056
TI  - Mechanosensitive miRNAs and Bone Formation.
AB  - Mechanical stimuli are required for the maintenance of skeletal integrity and
      bone mass. An increasing amount of evidence indicates that multiple regulators
      (e.g., hormone, cytoskeleton proteins and signaling pathways) are involved in the
      mechanical stimuli modulating the activities of osteogenic cells and the process
      of bone formation. Significantly, recent studies have showed that several
      microRNAs (miRNAs) were sensitive to various mechanical stimuli and played a
      crucial role in osteogenic differentiation and bone formation. However, the
      functional roles and further mechanisms of mechanosensitive miRNAs in bone
      formation are not yet completely understood. This review highlights the roles of
      mechanosensitive miRNAs in osteogenic differentiation and bone formation and
      underlines their potential therapeutic application for bone loss induced by the
      altering of mechanical stimuli.

PMID- 28767059
TI  - Hyperspectral and Radar Airborne Imagery over Controlled Release of Oil at Sea.
AB  - Remote sensing techniques are commonly used by Oil and Gas companies to monitor
      hydrocarbon on the ocean surface. The interest lies not only in exploration but
      also in the monitoring of the maritime environment. Occurrence of natural seeps
      on the sea surface is a key indicator of the presence of mature source rock in
      the subsurface. These natural seeps, as well as the oil slicks, are commonly
      detected using radar sensors but the addition of optical imagery can deliver
      extra information such as thickness and composition of the detected oil, which is
      critical for both exploration purposes and efficient cleanup operations. Today,
      state-of-the-art approaches combine multiple data collected by optical and radar
      sensors embedded on-board different airborne and spaceborne platforms, to ensure
      wide spatial coverage and high frequency revisit time. Multi-wavelength imaging
      system may create a breakthrough in remote sensing applications, but it requires
      adapted processing techniques that need to be developed. To explore performances
      offered by multi-wavelength radar and optical sensors for oil slick monitoring,
      remote sensing data have been collected by SETHI (Systeme Experimental de
      Teledection Hyperfrequence Imageur), the airborne system developed by ONERA (the
      French Aerospace Lab), during an oil spill cleanup exercise carried out in 2015
      in the North Sea, Europe. The uniqueness of this dataset lies in its high spatial
      resolution, low noise level and quasi-simultaneous acquisitions of different part
      of the EM spectrum. Specific processing techniques have been developed to extract
      meaningful information associated with oil-covered sea surface. Analysis of this
      unique and rich dataset demonstrates that remote sensing imagery, collected in
      both optical and microwave domains, allows estimating slick surface properties
      such as the age of the emulsion released at sea, the spatial abundance of oil and
      the relative concentration of hydrocarbons remaining on the sea surface.

PMID- 28767060
TI  - Hybrid Structure Multichannel All-Fiber Current Sensor.
AB  - We have experimentally developed a hybrid-structure multi-channel all-fiber
      current sensor with ordinary silica fiber using fiber loop architecture.
      According to the rationale of time division multiplexing, the sensor combines
      parallel and serial structures. The purpose of the hybrid-structure multi-channel
      all-fiber current sensor is to get more information from the different measured
      points simultaneously. In addition, the hybrid-structure fiber current sensor
      exhibited a good linear response for each channel. A three-channel experiment was
      performed in the study and showed that the system could detect different current
      positions. Each channel could individually detect the current and needed a
      separate calibration system. Furthermore, the three channels will not affect each
      other.

PMID- 28767057
TI  - Regulation of NKG2D-Dependent NK Cell Functions: The Yin and the Yang of Receptor
      Endocytosis.
AB  - Natural-killer receptor group 2, member D (NKG2D) is a well characterized natural
      killer (NK) cell activating receptor that recognizes several ligands poorly
      expressed on healthy cells but up-regulated upon stressing stimuli in the context
      of cancer or viral infection. Although NKG2D ligands represent danger signals
      that render target cells more susceptible to NK cell lysis, accumulating evidence
      demonstrates that persistent exposure to ligand-expressing cells causes the
      decrease of NKG2D surface expression leading to a functional impairment of NKG2D
      dependent NK cell functions. Upon ligand binding, NKG2D is internalized from the
      plasma membrane and sorted to lysosomes for degradation. However, receptor
      endocytosis is not only a mechanism of receptor clearance from the cell surface,
      but is also required for the proper activation of signalling events leading to
      the functional program of NK cells. This review is aimed at providing a summary
      of current literature relevant to the molecular mechanisms leading to NKG2D down
      modulation with particular emphasis given to the role of NKG2D endocytosis in
      both receptor degradation and signal propagation. Examples of chronic ligand
      induced down-regulation of NK cell activating receptors other than NKG2D,
      including natural cytotoxicity receptors (NCRs), DNAX accessory molecule-1
      (DNAM1) and CD16, will be also discussed.

PMID- 28767061
TI  - Bifurcatriol, a New Antiprotozoal Acyclic Diterpene from the Brown Alga
      Bifurcaria bifurcata.
AB  - Linear diterpenes that are commonly found in brown algae are of high
      chemotaxonomic and ecological importance. This study reports bifurcatriol (1), a
      new linear diterpene featuring two stereogenic centers isolated from the Irish
      brown alga Bifurcariabifurcata. The gross structure of this new natural product
      was elucidated based on its spectroscopic data (IR, 1D and 2D-NMR, HRMS). Its
      absolute configuration was identified by experimental and computational
      vibrational circular dichroism (VCD) spectroscopy, combined with the calculation
      of 13C-NMR chemical shielding constants. Bifurcatriol (1) was tested for in vitro
      antiprotozoal activity towards a small panel of parasites (Plasmodium falciparum,
      Trypanosoma brucei rhodesiense, T. cruzi, and Leishmania donovani) and
      cytotoxicity against mammalian primary cells. The highest activity was exerted
      against the malaria parasite P. falciparum (IC50 value 0.65 MUg/mL) with low
      cytotoxicity (IC50 value 56.6 MUg/mL). To our knowledge, this is the first
      successful application of VCD and DP4 probability analysis of the calculated 13C
      NMR chemical shifts for the simultaneous assignment of the absolute configuration
      of multiple stereogenic centers in a long-chain acyclic natural product.

PMID- 28767062
TI  - Dietary Flavonoid Intake Is Inversely Associated with Cardiovascular Disease Risk
      as Assessed by Body Mass Index and Waist Circumference among Adults in the United
      States.
AB  - Although flavonoids may confer anti-inflammatory and anti-oxidant benefits, no
      research has examined if flavonoid intake is related to cardiovascular disease
      (CVD) risk defined by anthropometric measures in the USA population. This study
      sought to determine whether flavonoid intake is associated with combined body
      mass index (BMI) and waist circumference (WC) measures indicative of high, very
      high, or extremely high ("high+") risk for CVD, using one day of 24-h recall data
      from adult (>=20 years) participants in What We Eat in America, National Health
      and Nutrition Examination Survey 2007-2010. Individuals were divided into
      categories of intake of total flavonoids and each flavonoid class, and adjusted
      estimates of the percentages at high+ CVD risk (based on BMI and WC, as per
      National Heart, Lung, and Blood Institute guidelines) were calculated. Inverse
      linear trends were found in percentages of adults at high+ CVD risk by intake of
      total flavonoids, anthocyanidins, flavan-3-ols, and flavanones (p < 0.01). For
      individuals in the highest (versus the lowest) intake category of anthocyanidins,
      flavan-3-ols, and flavanones, relative risk and confidence intervals (RR and CI,
      respectively) were 0.86 (99% CI: 0.79, 0.93), 0.88 (99% CI: 0.79, 0.98), and 0.89
      (99% CI: 0.80, 0.98), respectively. Research is needed to determine whether the
      inverse relationships found in this study are applicable to CVD endpoints at the
      population level.

PMID- 28767063
TI  - An Acquisition Scheme Based on a Matched Filter for Novel Communication and
      Navigation Fusion Signals.
AB  - In order to enhance the positioning capability of terrestrial networks, a novel
      communication and navigation fusion signal is proposed. The novel signal
      multiplexes the communication and navigation signal in the same frequency band,
      and the navigation system is superimposed on the original communication system.
      However, the application of pseudorandom noise (PRN) sequences in the navigation
      system is limited by the communication clock period. Taking the application of
      PRN sequences limited by the clock period as objects, the present study analyzes
      truncated PRN (TPRN) sequences. PRN sequences with a TPRN sequence as the
      navigation signal can overcome the communication system clock period limitation.
      Then, a matched filter algorithm with double detection (MFADD) is proposed to
      acquire the novel signal. The matched filter method is applied to the proposed
      algorithm to determine the start code phase of TPRN. Monte Carlo simulations and
      real data tests demonstrate the effectiveness of the proposed algorithm for the
      designed signal.

PMID- 28767064
TI  - Psoralea corylifolia L. Seed Extract Attenuates Diabetic Nephropathy by
      Inhibiting Renal Fibrosis and Apoptosis in Streptozotocin-Induced Diabetic Mice.
AB  - The Psoralea corylifolia L. seed (PCS) is a widely used herbal medicine, but its
      possible effect against diabetic nephropathy has not been studied. To investigate
      the anti-nephropathic effect of PCS extracts, we performed experiments using a
      diabetic mouse model and high glucose-treated mesangial cells. Streptozotocin
      (STZ)-induced diabetic mice were orally administered PCS extract for 8 weeks (500
      mg/kg/day). Increased creatinine clearance, urine volume, urine microalbumin, and
      mesangial expansion were observed in STZ-induced diabetic mice; these were
      significantly reduced by PCS extract administration. PCS extract significantly
      reduced fibrosis in the kidney tissue of diabetic mice as evidenced by decreased
      mRNA expression of collagen type IV-alpha2, fibronectin, PAI-1, and TGF-beta1. In
      addition, cleaved PARP, an apoptotic gene, was upregulated in the diabetic
      nephropathy mice, and this was ameliorated after PCS extract treatment. Treatment
      of high glucose-treated MES-13 cells with isopsoralen and psoralen, major
      components of PCS extract, also decreased the expression of fibrosis and
      apoptosis marker genes and increased cell viability. PCS extract exerts
      protective effects against STZ-induced diabetic nephropathy via anti-fibrotic and
      anti-apoptotic effects. PCS extract might be a potential pharmacological agent to
      protect against high glucose-induced renal damage under diabetic conditions.

PMID- 28767065
TI  - Do Multiwell Plate High Throughput Assays Measure Loss of Cell Viability
      Following Exposure to Genotoxic Agents?
AB  - Cell-based assays in multiwell plates are widely used for radiosensitivity and
      chemosensitivity assessment with different mammalian cell types. Despite their
      relative ease of performance, such assays lack specificity as they do not
      distinguish between the cytostatic (reversible/sustained growth arrest) and
      cytotoxic (loss of viability) effects of genotoxic agents. We recently reported
      studies with solid tumor-derived cell lines demonstrating that radiosensitivity
      as measured by multiwell plate colorimetric (e.g., XTT) and fluorimetric (e.g.,
      CellTiter-Blue) assays reflects growth arrest but not loss of viability. Herein
      we report similar observations with cancer cell lines expressing wild-type p53
      (A549 lung carcinoma) or mutant p53 (MDA-MB-231 breast carcinoma) after treatment
      with the chemotherapeutic drug cisplatin. Importantly, we show that treatment of
      cancer cells with concentrations of cisplatin that result in 50% effect (i.e.,
      IC50) in multiwell plate assays trigger the emergence of growth arrested cells
      that exhibit highly enlarged morphology, remain viable and adherent to the
      culture dish, and metabolize the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl-tetrazolium bromide (MTT) to its formazan derivative. The emergence
      of markedly enlarged viable cells complicates the interpretation of
      chemosensitivity data obtained with multiwell plate high throughput assays.
      Relying solely on IC50 values could be misleading.

PMID- 28767066
TI  - Isorhamnetin and Quercetin Derivatives as Anti-Acetylcholinesterase Principles of
      Marigold (Calendula officinalis) Flowers and Preparations.
AB  - Marigold (Calendula officinalis L.) is one of the most common and widespread
      plants used medicinally all over the world. The present study aimed to evaluate
      the anti-acetylcholinesterase activity of marigold flowers, detect the compounds
      responsible and perform chemical analysis of marigold commercial products.
      Analysis of 23 varieties of C. officinalis flowers introduced into Siberia
      allowed us to select the Greenheart Orange variety due to the superior content of
      flavonoids (46.87 mg/g) and the highest inhibitory activity against
      acetylcholinesterase (IC50 63.52 ug/mL). Flavonoids, isorhamnetin and quercetin
      derivatives were revealed as potential inhibitors with the application of high
      performance liquid chromatography (HPLC) activity-based profiling. Investigation
      of the inhibitory activity of isorhamnetin glycosides demonstrated the maximal
      potency for isorhamnetin-3-O-(2'',6''-di-acetyl)-glucoside (IC50 51.26 MUM) and
      minimal potency for typhaneoside (isorhamnetin-3-O-(2'',6''-di-rhamnosyl)
      glucoside; IC50 94.92 uM). Among quercetin derivatives, the most active compound
      was quercetin-3-O-(2'',6''-di-acetyl)-glucoside (IC50 36.47 uM), and the least
      active component was manghaslin (quercetin-3-O-(2'',6''-di-rhamnosyl)-glucoside;
      IC50 94.92 uM). Some structure-activity relationships were discussed. Analysis of
      commercial marigold formulations revealed a reduced flavonoid content (from 7.18
      19.85 mg/g) compared with introduced varieties. Liquid extract was the most
      enriched preparation, characterized by 3.10 mg/mL of total flavonoid content, and
      infusion was the least enriched formulation (0.41 mg/mL). The presented results
      suggest that isorhamnetin and quercetin and its glycosides can be considered as
      potential anti-acetylcholinesterase agents.

PMID- 28767067
TI  - Sinulariolide Suppresses Cell Migration and Invasion by Inhibiting Matrix
      Metalloproteinase-2/-9 and Urokinase through the PI3K/AKT/mTOR Signaling Pathway
      in Human Bladder Cancer Cells.
AB  - Sinulariolide is a natural product extracted from the cultured-type soft coral
      Sinularia flexibilis, and possesses bioactivity against the movement of several
      types of cancer cells. However, the molecular pathway behind its effects on human
      bladder cancer remain poorly understood. Using a human bladder cancer cell line
      as an in vitro model, this study investigated the underlying mechanism of
      sinulariolide against cell migration/invasion in TSGH-8301 cells. We found that
      sinulariolide inhibited TSGH-8301 cell migration/invasion, and the effect was
      concentration-dependent. Furthermore, the protein expressions of matrix
      metalloproteinases (MMPs) MMP-2 and MMP-9, as well as urokinase, were
      significantly decreased after 24-h sinulariolide treatment. Meanwhile, the
      increased expression of tissue inhibitors of metalloproteinases (TIMPs) TIMP-1
      and TIMP-2 were in parallel with an increased concentration of sinulariolide.
      Finally, the expressions of several key phosphorylated proteins in the mTOR
      signaling pathway were also downregulated by sinulariolide treatment. Our results
      demonstrated that sinulariolide has significant effects against TSGH-8301 cell
      migration/invasion, and its effects were associated with decreased levels of MMP
      2/-9 and urokinase expression, as well as increased TIMP-1/TIMP-2 expression. The
      inhibitory effects were mediated by reducing phosphorylation proteins of the
      PI3K, AKT, and mTOR signaling pathway. The findings suggested that sinulariolide
      is a good candidate for advanced investigation with the aim of developing a new
      drug for the treatment of human bladder cancer.

PMID- 28767068
TI  - Influence of Health Warnings on Beliefs about the Health Effects of Cigarette
      Smoking, in the Context of an Experimental Study in Four Asian Countries.
AB  - Cigarette package health warnings can be an important and low-cost means of
      communicating the health risks of smoking. We examined whether viewing health
      warnings in an experimental study influenced beliefs about the health effects of
      smoking, by conducting surveys with ~500 adult male smokers and ~500 male and
      female youth (age 16-18) in Beijing, China (n = 1070), Mumbai area, India (n =
      1012), Dhaka, Bangladesh (n = 1018), and Republic of Korea (n = 1362). Each
      respondent was randomly assigned to view and rate pictorial health warnings for 2
      of 15 different health effects, after which they reported beliefs about whether
      smoking caused 12 health effects. Respondents who viewed relevant health warnings
      (vs. other warnings) were significantly more likely to believe that smoking
      caused that particular health effect, for several health effects in each sample.
      Approximately three-quarters of respondents in China (Beijing), Bangladesh
      (Dhaka), and Korea (which had general, text-only warnings) thought that cigarette
      packages should display more health information, compared to approximately half
      of respondents in the Mumbai area, India (which had detailed pictorial warnings).
      Pictorial health warnings that convey the risk of specific health effects from
      smoking can increase beliefs and knowledge about the health consequences of
      smoking, particularly for health effects that are lesser-known.

PMID- 28767069
TI  - Recent Advances in the Inhibition of p38 MAPK as a Potential Strategy for the
      Treatment of Alzheimer's Disease.
AB  - P38 mitogen-activated protein kinase (MAPK) is a crucial target for chronic
      inflammatory diseases. Alzheimer's disease (AD) is characterized by the presence
      of amyloid plaques and neurofibrillary tangles in the brain, as well as
      neurodegeneration, and there is no known cure. Recent studies on the underlying
      biology of AD in cellular and animal models have indicated that p38 MAPK is
      capable of orchestrating diverse events related to AD, such as tau
      phosphorylation, neurotoxicity, neuroinflammation and synaptic dysfunction. Thus,
      the inhibition of p38 MAPK is considered a promising strategy for the treatment
      of AD. In this review, we summarize recent advances in the targeting of p38 MAPK
      as a potential strategy for the treatment of AD and envision possibilities of p38
      MAPK inhibitors as a fundamental therapeutics for AD.

PMID- 28767070
TI  - Various Mechanisms Involve the Nuclear Factor (Erythroid-Derived 2)-Like (NRF2)
      to Achieve Cytoprotection in Long-Term Cisplatin-Treated Urothelial Carcinoma
      Cell Lines.
AB  - Therapeutic efficacy of cisplatin-based chemotherapy for advanced-stage
      urothelial carcinoma (UC) is limited by drug resistance. The nuclear factor
      (erythroid-derived 2)-like 2 (NRF2) pathway is a major regulator of
      cytoprotective responses. We investigated its involvement in cisplatin resistance
      in long-term cisplatin treated UC cell lines (LTTs). Expression of NRF2 pathway
      components and targets was evaluated by qRT-PCR and western blotting in LTT
      sublines from four different parental cells. NRF2 transcriptional activity was
      determined by reporter assays and total glutathione (GSH) was quantified
      enzymatically. Effects of siRNA-mediated NRF2 knockdown on chemosensitivity were
      analysed by viability assays, gammaH2AX immunofluorescence, and flow cytometry.
      Increased expression of NRF2, its positive regulator p62/SQSTM1, and elevated
      NRF2 activity was observed in 3/4 LTTs, which correlated with KEAP1 expression.
      Expression of cytoprotective enzymes and GSH concentration were upregulated in
      some LTTs. NRF2 knockdown resulted in downregulation of cytoprotective enzymes
      and resensitised 3/4 LTTs towards cisplatin as demonstrated by reduced IC50
      values, increased gammaH2AX foci formation, and elevated number of apoptotic
      cells. In conclusion, while LTT lines displayed diversity in NRF2 activation,
      NRF2 signalling contributed to cisplatin resistance in LTT lines, albeit in
      diverse ways. Accordingly, inhibition of NRF2 can be used to resensitise UC cells
      to cisplatin, but responses in patients may likewise be variable.

PMID- 28767071
TI  - Intramitochondrial Ascorbic Acid Enhances the Formation of Mitochondrial
      Superoxide Induced by Peroxynitrite via a Ca2+-Independent Mechanism.
AB  - Exposure of U937 cells to peroxynitrite promotes mitochondrial superoxide
      formation via a mechanism dependent on both inhibition of complex III and
      increased mitochondrial Ca2+ accumulation. Otherwise inactive concentrations of
      the oxidant produced the same maximal effects in the presence of either complex
      III inhibitors or agents mobilizing Ca2+ from the ryanodine receptor and
      enforcing its mitochondrial accumulation. l-Ascorbic acid (AA) produced similar
      enhancing effects in terms of superoxide formation, DNA strand scission and
      cytotoxicity. However, AA failed to enhance the intra-mitochondrial concentration
      of Ca2+ and the effects observed in cells supplemented with peroxinitrite, while
      insensitive to manipulations preventing the mobilization of Ca2+, or the
      mitochondrial accumulation of the cation, were also detected in human monocytes
      and macrophages, which do not express the ryanodine receptor. In all these cell
      types, mitochondrial permeability transition-dependent toxicity was detected in
      cells exposed to AA/peroxynitrite and, based on the above criteria, these
      responses also appeared Ca2+-independent. The enhancing effects of AA are
      therefore similar to those mediated by bona fide complex III inhibitors, although
      the vitamin failed to directly inhibit complex III, and in fact enhanced its
      sensitivity to the inhibitory effects of peroxynitrite.

PMID- 28767073
TI  - Seismic and Restoration Assessment of Monumental Masonry Structures.
AB  - Masonry structures are complex systems that require detailed knowledge and
      information regarding their response under seismic excitations. Appropriate
      modelling of a masonry structure is a prerequisite for a reliable earthquake
      resistant design and/or assessment. However, modelling a real structure with a
      robust quantitative (mathematical) representation is a very difficult, complex
      and computationally-demanding task. The paper herein presents a new stochastic
      computational framework for earthquake-resistant design of masonry structural
      systems. The proposed framework is based on the probabilistic behavior of crucial
      parameters, such as material strength and seismic characteristics, and utilizes
      fragility analysis based on different failure criteria for the masonry material.
      The application of the proposed methodology is illustrated in the case of a
      historical and monumental masonry structure, namely the assessment of the seismic
      vulnerability of the Kaisariani Monastery, a byzantine church that was built in
      Athens, Greece, at the end of the 11th to the beginning of the 12th century.
      Useful conclusions are drawn regarding the effectiveness of the intervention
      techniques used for the reduction of the vulnerability of the case-study
      structure, by means of comparison of the results obtained.

PMID- 28767072
TI  - Insights into the Mechanisms Involved in Strong Hemorrhage and Dermonecrosis
      Induced by Atroxlysin-Ia, a PI-Class Snake Venom Metalloproteinase.
AB  - Hemorrhage is the most prominent effect of snake venom metalloproteinases (SVMPs)
      in human envenomation. The capillary injury is a multifactorial effect caused by
      hydrolysis of the components of the basement membrane (BM). The PI and PIII
      classes of SVMPs are abundant in viperid venoms and hydrolyze BM components.
      However, hemorrhage is associated mostly with PIII-class SVMPs that contain non
      catalytic domains responsible for the binding of SVMPs to BM proteins,
      facilitating enzyme accumulation in the tissue and enhancing its catalytic
      efficiency. Here we report on Atroxlysin-Ia, a PI-class SVMP that induces
      hemorrhagic lesions in levels comparable to those induced by Batroxrhagin (PIII
      class), and a unique SVMP effect characterized by the rapid onset of
      dermonecrotic lesions. Atroxlysin-Ia was purified from B. atrox venom, and
      sequence analyses indicated that it is devoid of non-catalytic domains and unable
      to bind to BM proteins as collagen IV and laminin in vitro or in vivo. The
      presence of Atroxlysin-Ia was diffuse in mice skin, and localized mainly in the
      epidermis with no co-localization with BM components. Nevertheless, the skin
      lesions induced by Atroxlysin-Ia were comparable to those induced by
      Batroxrhagin, with induction of leukocyte infiltrates and hemorrhagic areas soon
      after toxin injection. Detachment of the epidermis was more intense in skin
      injected with Atroxlysin-Ia. Comparing the catalytic activity of both toxins,
      Batroxrhagin was more active in the hydrolysis of a peptide substrate while
      Atroxlysin-Ia hydrolyzed more efficiently fibrin, laminin, collagen IV and
      nidogen. Thus, the results suggest that Atroxlysin-Ia bypasses the binding step
      to BM proteins, essential for hemorrhagic lesions induced by PII- and P-III class
      SVMPs, causing a significantly fast onset of hemorrhage and dermonecrosis, due to
      its higher proteolytic capacity on BM components.

PMID- 28767074
TI  - Comparative Study on Antistaphylococcal Activity of Lipopeptides in Various
      Culture Media.
AB  - Staphylococcus aureus bacteria are one of the leading microorganisms responsible
      for nosocomial infections as well as being the primary causative pathogen of skin
      and wound infections. Currently, the therapy of staphylococcal diseases faces
      many difficulties, due to a variety of mechanisms of resistance and virulence
      factors. Moreover, a number of infections caused by S. aureus are connected with
      biofilm formation that impairs effectiveness of the therapy. Short cationic
      lipopeptides that are designed on the basis of the structure of antimicrobial
      peptides are likely to provide a promising alternative to conventional
      antibiotics. Many research groups have proved a high antistaphylococcal potential
      of lipopeptides, however, the use of different protocols for determination of
      antimicrobial activity may be the reason for inconsistency of the results. The
      aim of this study was to learn how the use of various bacteriological media as
      well as solvents may affect activity of lipopeptides and their cyclic analogs.
      Obtained results showed a great impact of these variables. For example, cyclic
      analogs were more effective when dissolved in an aqueous solution of acetic acid
      and bovine serum albumin (BSA). The greater activity against planktonic cultures
      was found in brain-heart infusion broth (BHI) and tryptic-soy broth (TSB), while
      the antibiofilm activity was higher in the Mueller-Hinton medium.

PMID- 28767075
TI  - Micro-Mechanical Viscoelastic Properties of Crosslinked Hydrogels Using the Nano
      Epsilon Dot Method.
AB  - Engineering materials that recapitulate pathophysiological mechanical properties
      of native tissues in vitro is of interest for the development of biomimetic organ
      models. To date, the majority of studies have focused on designing hydrogels for
      cell cultures which mimic native tissue stiffness or quasi-static elastic moduli
      through a variety of crosslinking strategies, while their viscoelastic (time
      dependent) behavior has been largely ignored. To provide a more complete
      description of the biomechanical environment felt by cells, we focused on
      characterizing the micro-mechanical viscoelastic properties of crosslinked
      hydrogels at typical cell length scales. In particular, gelatin hydrogels
      crosslinked with different glutaraldehyde (GTA) concentrations were analyzed via
      nano-indentation tests using the nano-epsilon dot method. The experimental data
      were fitted to a Maxwell Standard Linear Solid model, showing that increasing GTA
      concentration results in increased instantaneous and equilibrium elastic moduli
      and in a higher characteristic relaxation time. Therefore, not only do gelatin
      hydrogels become stiffer with increasing crosslinker concentration (as reported
      in the literature), but there is also a concomitant change in their viscoelastic
      behavior towards a more elastic one. As the degree of crosslinking alters both
      the elastic and viscous behavior of hydrogels, caution should be taken when
      attributing cell response merely to substrate stiffness, as the two effects
      cannot be decoupled.

PMID- 28767076
TI  - Parametric Optimization of Lateral NIPIN Phototransistors for Flexible Image
      Sensors.
AB  - Curved image sensors, which are a key component in bio-inspired imaging systems,
      have been widely studied because they can improve an imaging system in various
      aspects such as low optical aberrations, small-form, and simple optics
      configuration. Many methods and materials to realize a curvilinear imager have
      been proposed to address the drawbacks of conventional imaging/optical systems.
      However, there have been few theoretical studies in terms of electronics on the
      use of a lateral photodetector as a flexible image sensor. In this paper, we
      demonstrate the applicability of a Si-based lateral phototransistor as the pixel
      of a high-efficiency curved photodetector by conducting various electrical
      simulations with technology computer aided design (TCAD). The single
      phototransistor is analyzed with different device parameters: the thickness of
      the active cell, doping concentration, and structure geometry. This work presents
      a method to improve the external quantum efficiency (EQE), linear dynamic range
      (LDR), and mechanical stability of the phototransistor. We also evaluated the
      dark current in a matrix form of phototransistors to estimate the feasibility of
      the device as a flexible image sensor. Moreover, we fabricated and demonstrated
      an array of phototransistors based on our study. The theoretical study and design
      guidelines of a lateral phototransistor create new opportunities in flexible
      image sensors.

PMID- 28767077
TI  - Gut-Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic
      liver disease in the pediatric age group, paralleling an obesity pandemic. A
      "multiple-hit" hypothesis has been invoked to explain its pathogenesis. The
      "first hit" is liver lipid accumulation in obese children with insulin
      resistance. In the absence of significant lifestyle modifications leading to
      weight loss and increased physical activity, other factors may act as "second
      hits" implicated in liver damage progression leading to more severe forms of
      inflammation and hepatic fibrosis. In this regard, the gut-liver axis (GLA) seems
      to play a central role. Principal players are the gut microbiota, its bacterial
      products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and
      altered intestinal permeability) may promote bacteria/bacterial product
      translocation into portal circulation, activation of inflammation via toll-like
      receptors signaling in hepatocytes, and progression from simple steatosis to non
      alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been
      attributed to the farnesoid X receptor, a nuclear transcriptional factor
      activated from bile acids chemically modified by gut microbiota (GM) enzymes. The
      individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of
      interest at all ages and especially in pediatrics to identify new therapeutic
      approaches in patients recalcitrant to lifestyle changes. Specific targeting of
      gut microbiota via pre-/probiotic supplementation, feces transplantation, and
      farnesoid X receptor modulation appear promising.

PMID- 28767078
TI  - Influence of Silica Fume Addition in the Long-Term Performance of Sustainable
      Cement Grouts for Micropiles Exposed to a Sulphate Aggressive Medium.
AB  - At present, sustainability is of major importance in the cement industry, and the
      use of additions such as silica fume as clinker replacement contributes towards
      that goal. Special foundations, and particularly micropiles, are one of the most
      suitable areas for the use of sustainable cements. The aim of this research is to
      analyse the effects in the very long-term (for 600 days) produced by sulphate
      attack in the microstructure of grouts for micropiles in which OPC (ordinary
      Portland cement) has been replaced by 5% and 10% silica fume. This line of study
      is building on a previous work, where these effects were studied in slag and fly
      ash grouts. Grouts made using a commercial sulphate-resisting Portland cement
      were also studied. The non-destructive impedance spectroscopy technique, mercury
      intrusion porosimetry, and Wenner resistivity testing were used. Mass variation
      and the compressive strength have also been analysed. Apparently, impedance
      spectroscopy is the most suitable technique for studying sulphate attack
      development. According to the results obtained, grouts for micropiles with a
      content of silica fume up to 10% and exposed to an aggressive sulphate medium,
      have a similar or even better behaviour in the very long-term, compared to grouts
      prepared using sulphate-resisting Portland cement.

PMID- 28767079
TI  - Three New Sesquiterpene Glycosides from the Rhizomes of Trillium tschonoskii.
AB  - Three new sesquiterpene glycosides, possessing a rare aglycone with a sulfonyl
      between C-1 and C-15 positions, named 3-(3'E-7'R,8'-dihydroxy-4',8'-dimethyl-3'
      nonenyl)-2,5-dihydro-1,1-dioxo-thiophen 7'-O-beta-d-glucopyranosyl-(1->4)-O-beta
      d-glucopyranosyl-(1->4)-O-beta-d-glucopyranoside (1), 3-(3'E-7'R,8'-dihydroxy
      4',8'-dimethyl-3'-nonenyl)-2,5-dihydro-1,1-dioxo-thiophen 7'-O-beta-d
      glucopyranosyl-(1->4)-O-beta-d-glucopyranoside (2), and 3-(3'E-7'R,8'-dihydroxy
      4',8'-dimethyl-3'-nonenyl)-2,5-dihydro-1,1-dioxo-thiophen 7'-O-beta-d
      glucopyranosyl-6'-O-acetyl-(1->4)-O-beta-d-glucopyranosyl-(1->4)-O-beta-d
      glucopyranoside (3), respectively, were isolated from the rhizomes of Trillium
      tschonoskii. Their structures were established on the basis of spectroscopic
      data, including HR-ESI-MS, IR, 1D and 2D NMR. The cytotoxic properties of the
      three compounds were investigated using human hepatic L02 cells.

PMID- 28767080
TI  - Intrapancreatic Parenchymal Injection of Cells as a Useful Tool for Allowing a
      Small Number of Proliferative Cells to Grow In Vivo.
AB  - In vivo inoculation of cells such as tumor cells and induced pluripotent stem
      (iPS)/embryonic stem (ES) cells into immunocompromised mice has been considered
      as a powerful technique to evaluate their potential to proliferate or
      differentiate into various cell types originating from three germ cell layers.
      Subcutaneous grafting and grafting under the kidney capsule have been widely used
      for this purpose, but there are some demerits such as the requirement of a large
      number of tumor cells for inoculation and frequent failure of tumorigenesis.
      Therefore, grafting into other sites has been explored, including intratesticular
      or intramuscular grafting as well as grafting into the cochleae, liver, or
      salivary glands. In this study, we found that intrapancreatic parenchymal
      injection of cells is useful for allowing a small number of cells (~15 * 103
      cells or ~30 cell clumps MUL-1.site-1) to proliferate and sometimes differentiate
      into various types of cells. It requires only surgical exposure of the pancreas
      over the dorsal skin and subsequent injection of cells towards the pancreatic
      parenchyma under dissecting microscope-based observation using a mouthpiece
      controlled glass micropipette. We now name this technology "intrapancreatic
      parenchymal cell transplantation (IPPCT)", which will be useful, especially when
      only a small number of cells or colonies are available.

PMID- 28767082
TI  - Mechanical Contact Characteristics of PC3 Human Prostate Cancer Cells on Complex
      Shaped Silicon Micropillars.
AB  - In this study we investigated the contact characteristics of human prostate
      cancer cells (PC3) on silicon micropillar arrays with complex shapes by using
      high-resolution confocal fluorescence microscopy techniques. These arrays consist
      of micropillars that are of various cross-sectional geometries which produce
      different deformation profiles in adherent cells. Fluorescence micrographs reveal
      that some DAPI (4',6-diamidino-2-phenylindole)-stained nuclei from cells attached
      to the pillars develop nanometer scale slits and contain low concentrations of
      DNA. The lengths of these slits, and their frequency of occurrence, were
      characterized for various cross-sectional geometries. These DNA-depleted features
      are only observed in locations below the pillar's top surfaces. Results produced
      in this study indicate that surface topography can induce unique nanometer scale
      features in the PC3 cell.

PMID- 28767083
TI  - Full-Duplex Cooperative Sensing for Spectrum-Heterogeneous Cognitive Radio
      Networks.
AB  - In cognitive radio networks (CRNs), spectrum sensing is critical for guaranteeing
      that the opportunistic spectrum access by secondary users (SUs) will not
      interrupt legitimate primary users (PUs). The application of full-duplex radio to
      spectrum sensing enables SU to carry out sensing and transmission simultaneously,
      improving both spectrum awareness and CRN throughput. However, the issue of
      spectrum sensing with full-duplex radios deployed in heterogeneous environments,
      where SUs may observe different spectrum activities, has not been addressed. In
      this paper, we give a first look into this problem and develop a light-weight
      cooperative sensing framework called PaCoSIF, which involves only a pairwise SU
      transmitter (SU-Tx) and its receiver (SU-Rx) in cooperation. A dedicated control
      channel is not required for pairwise cooperative sensing with instantaneous
      feedback (PaCoSIF) because sensing results are collected and fused via the
      reverse channel provided by full-duplex radios. We present a detailed protocol
      description to illustrate how PaCoSIF works. However, it is a challenge to
      optimize the sensing performance of PaCoSIF since the two sensors suffer from
      spectrum heterogeneity and different kinds of interference. Our goal is to
      minimize the false alarm rate of PaCoSIF given the bound on the missed detection
      rate by adaptively adjusting the detection threshold of each sensor. We derive an
      expression for the optimal threshold using the Lagrange method and propose a fast
      binary-searching algorithm to solve it numerically. Simulations show that, with
      perfect signal-to-interference-and-noise-ratio (SINR) information, PaCoSIF could
      decrease the false alarm rate and boost CRN throughput significantly against
      conventional cooperative sensing when SUs are deployed in spectrum-heterogeneous
      environments. Finally, the impact of SINR error upon the performance of PaCoSIF
      is evaluated via extensive simulations.

PMID- 28767081
TI  - New Insights in the Design of Bioactive Peptides and Chelating Agents for Imaging
      and Therapy in Oncology.
AB  - Many synthetic peptides have been developed for diagnosis and therapy of human
      cancers based on their ability to target specific receptors on cancer cell
      surface or to penetrate the cell membrane. Chemical modifications of amino acid
      chains have significantly improved the biological activity, the stability and
      efficacy of peptide analogues currently employed as anticancer drugs or as
      molecular imaging tracers. The stability of somatostatin, integrins and bombesin
      analogues in the human body have been significantly increased by cyclization
      and/or insertion of non-natural amino acids in the peptide sequences. Moreover,
      the overall pharmacokinetic properties of such analogues and others (including
      cholecystokinin, vasoactive intestinal peptide and neurotensin analogues) have
      been improved by PEGylation and glycosylation. Furthermore, conjugation of those
      peptide analogues to new linkers and bifunctional chelators (such as AAZTA, TETA,
      TRAP, NOPO etc.), produced radiolabeled moieties with increased half life and
      higher binding affinity to the cognate receptors. This review describes the most
      important and recent chemical modifications introduced in the amino acid
      sequences as well as linkers and new bifunctional chelators which have
      significantly improved the specificity and sensitivity of peptides used in
      oncologic diagnosis and therapy.

PMID- 28767084
TI  - Sc-Decorated Porous Graphene for High-Capacity Hydrogen Storage: First-Principles
      Calculations.
AB  - The generalized gradient approximation (GGA) function based on density functional
      theory is adopted to investigate the optimized geometrical structure, electron
      structure and hydrogen storage performance of Sc modified porous graphene (PG).
      It is found that the carbon ring center is the most stable adsorbed position for
      a single Sc atom on PG, and the maximum number of adsorbed H2 molecules is four
      with the average adsorption energy of -0.429 eV/H2. By adding a second Sc atom on
      the other side of the system, the hydrogen storage capacity of the system can be
      improved effectively. Two Sc atoms located on opposite sides of the PG carbon
      ring center hole is the most suitable hydrogen storage structure, and the
      hydrogen storage capacity reach a maximum 9.09 wt % at the average adsorption
      energy of -0.296 eV/H2. The adsorption of H2 molecules in the PG system is mainly
      attributed to orbital hybridization among H, Sc, and C atoms, and Coulomb
      attraction between negatively charged H2 molecules and positively charged Sc
      atoms.

PMID- 28767085
TI  - Synthesis of Bi2S3/BiVO4 Heterojunction with a One-Step Hydrothermal Method Based
      on pH Control and the Evaluation of Visible-Light Photocatalytic Performance.
AB  - The band gaps of bismuth vanadate (BiVO4) and bismuth sulfide (Bi2S3) are about
      2.40 eV and 1.30 eV, respectively. Although both BiVO4 and Bi2S3 are capable of
      strong visible light absorption, electron-hole recombination occurs easily. To
      solve this problem, we designed a one-step hydrothermal method for synthesizing a
      Bismuth sulfide (Bi2S3)/Bismuth vanadate (BiVO4) heterojunction using
      polyvinylpyrrolidone K-30 (PVP) as a structure-directing agent, and 2-Amino-3
      mercaptopropanoic acid (l-cysteine) as a sulfur source. The pH of the reaction
      solution was regulated to yield different products: when the pH was 7.5, only
      monoclinic BiVO4 was produced (sample 7.5); when the pH was 8.0 or 8.5, both
      Bi2S3 and BiVO4 were produced (samples 8.0 and 8.5); and when the pH was 9.0,
      only Bi2S3 was produced (sample 9.0). In sample 8.0, Bi2S3 and BiVO4 were closely
      integrated with each other, with Bi2S3 particles formed on the surface of
      concentric BiVO4 layers, but the two compounds grew separately in a pH solution
      of 8.5. Visible-light photocatalytic degradation experiments demonstrated that
      the degradation efficiency of the Bi2S3/BiVO4 heterojunction was highest when
      prepared under a pH of 8.0. The initial rhodamine B in the solution (5 mg/L) was
      completely degraded within three hours. Recycling experiments verified the high
      stability of Bi2S3/BiVO4. The synthesis method proposed in this paper is expected
      to enable large-scale and practical use of Bi2S3/BiVO4.

PMID- 28767086
TI  - Effect of Smoking Behavior before and during Pregnancy on Selected Birth Outcomes
      among Singleton Full-Term Pregnancy: A Murmansk County Birth Registry Study.
AB  - The aim of our study was to assess associations between smoking behavior before
      and during pregnancy and selected adverse birth outcomes. This study is based on
      the Murmansk County Birth Registry (MCBR). Our study includes women who delivered
      a singleton pregnancy after 37 weeks of gestation (N = 44,486). Smoking
      information was self-reported and assessed at the first antenatal visit during
      pregnancy. We adjusted for potential confounders using logistic regression. The
      highest proportion of infants with low values of birth weight, birth length, head
      circumference, ponderal index and of the Apgar score at 5 min was observed for
      women who smoked both before and during pregnancy. We observed a dose-response
      relationship between the number of cigarettes smoked per day during pregnancy and
      the odds of the aforementioned adverse birth outcomes; neither were there
      significant differences in their occurrences among non-smokers and those who
      smoked before but not during pregnancy. Moreover, smoking reduction during
      pregnancy relative to its pre-gestation level did not influence the odds of the
      adverse birth outcomes. Our findings emphasize a continued need for action
      against tobacco smoking during pregnancy.

PMID- 28767087
TI  - Novel Methylselenoesters as Antiproliferative Agents.
AB  - Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly,
      the biological effects of Se compounds are exerted by their metabolites, with
      methylselenol (CH3SeH) being one of the key executors. In this study, we
      developed a new series of methylselenoesters with different scaffolds aiming to
      modulate the release of CH3SeH. The fifteen compounds follow Lipinski's Rule of
      Five and with exception of compounds 1 and 14, present better drug-likeness
      values than the positive control methylseleninic acid. The compounds were
      evaluated to determine their radical scavenging activity. Compound 11 reduced
      both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a
      panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary
      adenocarcinoma and chronic myelogenous leukemia) and two non-malignant (lung and
      mammary epithelial) cell lines. Ten compounds had GI50 values below 10 MUM at 72
      h in four cancer cell lines. Compounds 5 and 15 were chosen for further
      characterization of their mechanism of action in the mammary adenocarcinoma cell
      line due to their similarity with methylseleninic acid. Both compounds induced
      G2/M arrest whereas cell death was partially executed by caspases. The reduction
      and metabolism were also investigated, and both compounds were shown to be
      substrates for redox active enzyme thioredoxin reductase.

PMID- 28767089
TI  - Combining Multi-Agent Systems and Wireless Sensor Networks for Monitoring Crop
      Irrigation.
AB  - Monitoring mechanisms that ensure efficient crop growth are essential on many
      farms, especially in certain areas of the planet where water is scarce. Most
      farmers must assume the high cost of the required equipment in order to be able
      to streamline natural resources on their farms. Considering that many farmers
      cannot afford to install this equipment, it is necessary to look for more
      effective solutions that would be cheaper to implement. The objective of this
      study is to build virtual organizations of agents that can communicate between
      each other while monitoring crops. A low cost sensor architecture allows farmers
      to monitor and optimize the growth of their crops by streamlining the amount of
      resources the crops need at every moment. Since the hardware has limited
      processing and communication capabilities, our approach uses the PANGEA
      architecture to overcome this limitation. Specifically, we will design a system
      that is capable of collecting heterogeneous information from its environment,
      using sensors for temperature, solar radiation, humidity, pH, moisture and wind.
      A major outcome of our approach is that our solution is able to merge
      heterogeneous data from sensors and produce a response adapted to the context. In
      order to validate the proposed system, we present a case study in which farmers
      are provided with a tool that allows us to monitor the condition of crops on a TV
      screen using a low cost device.

PMID- 28767088
TI  - A Simple and Inexpensive Electrochemical Assay for the Identification of Nitrogen
      Containing Explosives in the Field.
AB  - We report a simple and inexpensive electrochemical assay using a custom built
      hand-held potentiostat for the identification of explosives. The assay is based
      on a wipe test and is specifically designed for use in the field. The prototype
      instrument designed to run the assay is capable of performing time-resolved
      electrochemical measurements including cyclic square wave voltammetry using an
      embedded microcontroller with parts costing roughly $250 USD. We generated an
      example library of cyclic square wave voltammograms of 12 compounds including 10
      nitroaromatics, a nitramine (RDX), and a nitrate ester (nitroglycine), and
      designed a simple discrimination algorithm based on this library data for
      identification.

PMID- 28767090
TI  - A Magnetic-Balanced Inductive Link for the Simultaneous Uplink Data and Power
      Telemetry.
AB  - When using the conventional two-coil inductive link for the simultaneous wireless
      power and data transmissions in implantable biomedical sensor devices, the strong
      power carrier could overwhelm the uplink data signal and even saturate the
      external uplink receiver. To address this problem, we propose a new magnetic
      balanced inductive link for our implantable glaucoma treatment device. In this
      inductive link, an extra coil is specially added for the uplink receiving. The
      strong power carrier interference is minimized to approach zero by balanced
      canceling of the magnetic field of the external power coil. The implant coil is
      shared by the wireless power harvesting and the uplink data transmitting. Two
      carriers (i.e., 2-MHz power carrier and 500-kHz uplink carrier) are used for the
      wireless power transmission and the uplink data transmission separately. In the
      experiments, the prototype of this link achieves as high as 65.72 dB improvement
      of the signal-to-interference ratio (SIR) compared with the conventional two-coil
      inductive link. Benefiting from the significant improvement of SIR, the implant
      transmitter costs only 0.2 mW of power carrying 50 kbps of binary phase shift
      keying data and gets a bit error rate of 1 * 10 - 7 , even though the coupling
      coefficient is as low as 0.005. At the same time, 5 mW is delivered to the load
      with maximum power transfer efficiency of 58.8%. This magnetic-balanced inductive
      link is useful for small-sized biomedical sensor devices, which require
      transmitting data and power simultaneously under ultra-weak coupling.

PMID- 28767091
TI  - Heart Rate Detection Using Microsoft Kinect: Validation and Comparison to
      Wearable Devices.
AB  - Contactless detection is one of the new frontiers of technological innovation in
      the field of healthcare, enabling unobtrusive measurements of biomedical
      parameters. Compared to conventional methods for Heart Rate (HR) detection that
      employ expensive and/or uncomfortable devices, such as the Electrocardiograph
      (ECG) or pulse oximeter, contactless HR detection offers fast and continuous
      monitoring of heart activities and provides support for clinical analysis without
      the need for the user to wear a device. This paper presents a validation study
      for a contactless HR estimation method exploiting RGB (Red, Green, Blue) data
      from a Microsoft Kinect v2 device. This method, based on Eulerian Video
      Magnification (EVM), Photoplethysmography (PPG) and Videoplethysmography (VPG),
      can achieve performance comparable to classical approaches exploiting wearable
      systems, under specific test conditions. The output given by a Holter, which
      represents the gold-standard device used in the test for ECG extraction, is
      considered as the ground-truth, while a comparison with a commercial smartwatch
      is also included. The validation process is conducted with two modalities that
      differ for the availability of a priori knowledge about the subjects' normal HR.
      The two test modalities provide different results. In particular, the HR
      estimation differs from the ground-truth by 2% when the knowledge about the
      subject's lifestyle and his/her HR is considered and by 3.4% if no information
      about the person is taken into account.

PMID- 28767092
TI  - Molecular Identification of Gambierdiscus and Fukuyoa (Dinophyceae) from
      Environmental Samples.
AB  - Ciguatera Fish Poisoning (CFP) is increasing across the Pacific and the
      distribution of the causative dinoflagellates appears to be expanding. Subtle
      differences in thecal plate morphology are used to distinguish dinoflagellate
      species, which are difficult to determine using light microscopy. For these
      reasons we sought to develop a Quantitative PCR assay that would detect all
      species from both Gambierdiscus and Fukuyoa genera in order to rapidly screen
      environmental samples for potentially toxic species. Additionally, a specific
      assay for F. paulensis was developed as this species is of concern in New Zealand
      coastal waters. Using the assays we analyzed 31 samples from three locations
      around New Zealand and the Kingdom of Tonga. Fourteen samples in total were
      positive for Gambierdiscus/Fukuyoa and two samples were also positive using the
      F. paulensis assay. Samples from the Kermadec Islands were further characterized
      using high-throughput sequencing metabarcoding. The majority of reads
      corresponded to Gambierdiscus species with three species identified at all sites
      (G. australes, G. honu and G. polynesiensis). This is the first confirmed
      identification of G. polynesiensis, a known ciguatoxin producer, in New Zealand
      waters. Other known toxin-producing genera were also detected, included
      Alexandrium, Amphidinium, Azadinium, Dinophysis, Ostreopsis, and Prorocentrum.

PMID- 28767093
TI  - Investigating the Spatial Dimension of Food Access.
AB  - The purpose of this article is to investigate the sensitivity of food access
      models to a dataset's spatial distribution and the empirical definition of food
      access, which contributes to understanding the mixed findings of previous
      studies. Data was collected in the Dan River Region in the United States using a
      telephone survey for individual-level variables (n = 784) and a store audit for
      the location of food retailers and grocery store quality. Spatial scanning
      statistics assessed the spatial distribution of obesity and detected a cluster of
      grocery stores overlapping with a cluster of obesity centered on a grocery store
      suggesting that living closer to a grocery store increased the likelihood of
      obesity. Logistic regression further examined this relationship while controlling
      for demographic and other food environment variables. Similar to the cluster
      analysis results, increased distance to a grocery store significantly decreased
      the likelihood of obesity in the urban subsample (average marginal effects, AME =
      -0.09, p-value = 0.02). However, controlling for grocery store quality nullified
      these results (AME = -0.12, p-value = 0.354). Our findings suggest that measuring
      grocery store accessibility as the distance to the nearest grocery store captures
      variability in the spatial distribution of the health outcome of interest that
      may not reflect a causal relationship between the food environment and health.

PMID- 28767094
TI  - Depressive Symptoms and Length of U.S. Residency Are Associated with Obesity
      among Low-Income Latina Mothers: A Cross-Sectional Analysis.
AB  - Latinos are the largest minority population group in the United States (U.S.),
      and low-income Latina women are at elevated risk of depression and obesity. Thus,
      the prevention of these two problems is a pressing public health concern in this
      population. Both depressive symptoms and obesity are modifiable factors that can
      be addressed by culturally relevant interventions. However, the association
      between depressive symptoms and obesity in Latina immigrant women is not well
      understood. Therefore, this cross-sectional study examined the association
      between depressive symptoms and obesity among Latina women of childbearing age
      (15-44). Participants (n = 147) were low-income, predominantly immigrant Latina
      mothers enrolled in the Latina Mothers' Child Feeding Practices and Style Study.
      Women were eligible to participate if they self-identified as Latina; were
      enrolled in or eligible for the Special Supplemental Nutrition Program for Women,
      Infants and Children program; had a child between ages two and five years; and
      were living in the U.S. for at least one year, and residing in Rhode Island.
      Enrolled participants completed a survey in their language of preference (English
      or Spanish) administered by bilingual interviewers. About one-third (34%) of
      participants were classified as having obesity (BMI >= 30 kg/m2), 28.3% had
      elevated depressive symptoms (CES-D >= 16), and 70.1% were immigrants. Women with
      elevated depressive symptoms had increased odds of having obesity (odds ratio
      (OR) = 2.80, 95% confidence interval (CI): 1.24-6.33). Additionally, among
      immigrants, length of U.S. residency was associated with increased odds of
      obesity (OR = 1.05, 95% CI: 1.02-1.09). Findings underscore the need for
      screening and culturally relevant interventions designed to address both
      depressive symptoms and obesity among low-income Latina women of childbearing
      age. Furthermore, findings highlight the importance of taking into account the
      length of residency in the U.S. when designing interventions targeting Latina
      immigrants.

PMID- 28767095
TI  - The Combined Effects of Aircraft and Road Traffic Noise and Aircraft and Railway
      Noise on Noise Annoyance-An Analysis in the Context of the Joint Research
      Initiative NORAH.
AB  - The Noise Related Annoyance Cognition and Health (NORAH) research initiative is
      one of the most extensive studies on the physiological and psychological long
      term effects of transportation noise in Europe. It includes research on the
      quality of life and annoyance as well as cardiovascular effects, sleep
      disturbance, breast cancer, blood pressure, depression and the cognitive
      development of children. Within the realm of the annoyance module of the study
      approximately 10,000 residents of the Rhine-Main district were surveyed on the
      combined effects of transportation noise. This included combined noise from
      aircraft and road traffic noise (N = 4905), or aircraft and railway noise (N =
      4777). Results show that judgment of the total noise annoyance of participants
      was strongly determined by the sound source which was judged as more annoying (in
      this case aircraft noise). To a lesser extent, the average sound pressure level
      of the two present sources was also of relevance.

PMID- 28767096
TI  - Water Environment Assessment as an Ecological Red Line Management Tool for Marine
      Wetland Protection.
AB  - A 'red line' was established, identifying an area requiring for ecological
      protection in Tianjin, China. Within the protected area of the red line area, the
      Qilihai wetland is an important ecotope with complex ecological functions,
      although the ecosystem is seriously disturbed due to anthropogenic activities in
      the surrounding areas. This study assesses the water quality status of the
      Qilihai wetlands to identify the pollution sources and potential improvements
      based on the ecological red line policy, to improve and protect the waters of the
      Qilihai wetlands. An indicator system was established to assess water quality
      status using single factor evaluation and a comprehensive evaluation method,
      supported by data from 2010 to 2013. Assessment results show that not all
      indicators met the requirement of the Environmental Quality Standards for Surface
      Water (GB3838-2002) and that overall, waters in the Qilihai wetland were
      seriously polluted. Based on these findings we propose restrictions on all
      polluting anthropogenic activities in the red line area and implementation of
      restoration projects to improve water quality.

PMID- 28767097
TI  - Sympathetic Overactivity in Chronic Kidney Disease: Consequences and Mechanisms.
AB  - The incidence of chronic kidney disease (CKD) is increasing worldwide, with more
      than 26 million people suffering from CKD in the United States alone. More
      patients with CKD die of cardiovascular complications than progress to dialysis.
      Over 80% of CKD patients have hypertension, which is associated with increased
      risk of cardiovascular morbidity and mortality. Another common, perhaps
      underappreciated, feature of CKD is an overactive sympathetic nervous system.
      This elevation in sympathetic nerve activity (SNA) not only contributes to
      hypertension but also plays a detrimental role in the progression of CKD
      independent of any increase in blood pressure. Indeed, high SNA is associated
      with poor prognosis and increased cardiovascular morbidity and mortality
      independent of its effect on blood pressure. This brief review will discuss some
      of the consequences of sympathetic overactivity and highlight some of the
      potential pathways contributing to chronically elevated SNA in CKD. Mechanisms
      leading to chronic sympathoexcitation in CKD are complex, multifactorial and to
      date, not completely understood. Identification of the mechanisms and/or signals
      leading to sympathetic overactivity in CKD are crucial for development of
      effective therapeutic targets to reduce the increased cardiovascular risk in this
      patient group.

PMID- 28767098
TI  - Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes.
AB  - Nucleic acid aptamers have minimal immunogenicity, high chemical synthesis
      production, low cost and high chemical stability when compared with antibodies.
      However, the susceptibility to nuclease degradation, rapid excretion through
      renal filtration and insufficient binding affinity hindered their development as
      drug candidates for therapeutic applications. In this review, we will discuss
      methods to conquer these challenges and highlight recent developments of chemical
      modifications and technological advances that may enable early aptamers to be
      translated into clinical therapeutics.

PMID- 28767100
TI  - Adsorption of Milk Proteins (beta-Casein and beta-Lactoglobulin) and BSA onto
      Hydrophobic Surfaces.
AB  - Here, we study films of proteins over planar surfaces and protein-coated
      microspheres obtained from the adsorption of three different proteins ( beta 
      casein, beta -lactoglobulin and bovine serum albumin (BSA)). The investigation of
      protein films in planar surfaces is performed by combining quartz crystal
      microbalance (QCM) and atomic force microscopy (AFM) measurements with all-atomic
      molecular dynamics (MD) simulations. We found that BSA and beta -lactoglobulin
      form compact monolayers, almost without interstices between the proteins.
      However, beta -casein adsorbs forming multilayers. The study of the
      electrokinetic mobility of protein-coated latex microspheres shows substantial
      condensation of ions from the buffer over the complexes, as predicted from ion
      condensation theories. The electrokinetic behavior of the latex-protein complexes
      is dominated by the charge of the proteins and the phenomenon of ion
      condensation, whereas the charge of the latex colloids plays only a minor role.

PMID- 28767099
TI  - Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in
      Human Renal Carcinoma Caki Cells.
AB  - Fisetin is a natural compound found in fruits and vegetables such as
      strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer
      effects, including anti-proliferation and anti-migration, we investigated whether
      fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly
      induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP),
      which is a marker of apoptosis, and increased caspase activation. We found that
      pan-caspase inhibitor (z-VAD-fmk) inhibited fisetin-induced apoptosis. In
      addition, fisetin induced death receptor 5 (DR5) expression at the
      transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin
      induced apoptosis. Furthermore, fisetin induced p53 protein expression through up
      regulation of protein stability, whereas down-regulation of p53 by siRNA markedly
      inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up
      regulation of CHOP expression and reactive oxygen species production, which had
      no effect on fisetin-induced apoptosis. Taken together, our study demonstrates
      that fisetin induced apoptosis through p53 mediated up-regulation of DR5
      expression at the transcriptional level.

PMID- 28767101
TI  - Integrating Optimal Heterogeneous Sensor Deployment and Operation Strategies for
      Dynamic Origin-Destination Demand Estimation.
AB  - Most existing network sensor location problem (NSLP) models are designed to
      identify the number of sensors with fixed costs and installation locations, and
      sensors are assumed to be installed permanently. However, sometimes sensors are
      carried by individuals to collect traffic data measurements manually at fixed
      locations. Hence, their duration of operation for which traffic data measurements
      are collected is limited, and their costs are not fixed as they are correlated
      with the duration of operation. This paper proposes a NSLP model that integrates
      optimal heterogeneous sensor deployment and operation strategies for the dynamic
      O-D demand estimates under budget constraints. The deployment strategy consists
      of the numbers of link and node sensors and their installation locations. The
      operation strategy includes sensors' start time and duration of operation, which
      has not been addressed in previous studies. An algorithm is developed to solve
      the proposed model. Numerical experiments performed on a network from a part of
      Chennai, India show that the proposed model can identify the optimal
      heterogeneous sensor deployment and operation strategies with the maximum dynamic
      O-D demand estimation accuracy.

PMID- 28767102
TI  - Allocation to male vs female floral function varies by currency and responds
      differentially to density and moisture stress.
AB  - Allocation of finite resources to separate reproductive functions is predicted to
      vary across environments and affect fitness. Biomass is the most commonly
      measured allocation currency; however, in comparison with nutrients it may be
      less limited and express different environmental and evolutionary responses.
      Here, we measured carbon, nitrogen, phosphorus, and biomass allocation among
      floral whorls in recombinant inbred lines of Brassica rapa in multiple
      environments to characterize the genetic architecture of floral allocation,
      including its sensitivity to environmental heterogeneity and to choice of
      currency. Mass, carbon, and nitrogen allocation to female whorls (pistils and
      sepals) decreased under high density, whereas nitrogen allocation to male organs
      (stamens) decreased under drought. Phosphorus allocation decreased by half in
      pistils under drought, while stamen phosphorus was unaffected by environment.
      While the contents of each currency were positively correlated among whorls,
      selection to improve fitness through female (or male) function typically favored
      increased allocation to pistils (or stamens) but decreased allocation to other
      whorls. Finally, genomic regions underlying correlations among allocation metrics
      were mapped, and loci related to nitrogen uptake and floral organ development
      were located within mapped quantitative trait loci. Our candidate gene
      identification suggests that nutrient uptake may be a limiting step in
      maintaining male allocation. Taken together, allocation to male vs female
      function is sensitive to distinct environmental stresses, and the choice of
      currency affects the interpretation of floral allocation responses to the
      environment. Further, genetic correlations may counter the evolution of
      allocation patterns that optimize fitness through female or male function.

PMID- 28767103
TI  - AFLP diversity and spatial structure of Calycophyllum candidissimum (Rubiaceae),
      a dominant tree species of Nicaragua's critically endangered seasonally dry
      forest.
AB  - The Central American seasonally dry tropical (SDT) forest biome is one of the
      worlds' most endangered ecosystems, yet little is known about the genetic
      consequences of its recent fragmentation. A prominent constituent of this biome
      is Calycophyllum candidissimum, an insect-pollinated and wind-dispersed canopy
      tree of high socio-economic importance, particularly in Nicaragua. Here, we
      surveyed amplified fragment length polymorphisms across 13 populations of this
      species in Nicaragua to elucidate the relative roles of contemporary vs
      historical factors in shaping its genetic variation. Genetic diversity was low in
      all investigated populations (mean HE=0.125), and negatively correlated with
      latitude. Overall population differentiation was moderate (PhiST=0.109, P<0.001),
      and Bayesian analysis of population structure revealed two major latitudinal
      clusters (I: 'Pacific North'+'Central Highland'; II: 'Pacific South'), along with
      a genetic cline between I and II. Population-based cluster analyses indicated a
      strong pattern of 'isolation by distance' as confirmed by Mantel's test. Our
      results suggest that (1) the low genetic diversity of these populations reflects
      biogeographic/population history (colonisation from South America, Pleistocene
      range contractions) rather than recent human impact; whereas (2) the underlying
      process of their isolation by distance pattern, which is best explained by
      'isolation by dispersal limitation', implies contemporary gene flow between
      neighbouring populations as likely facilitated by the species' efficient seed
      dispersal capacity. Overall, these results underscore that even tree species from
      highly decimated forest regions may be genetically resilient to habitat
      fragmentation due to species-typical dispersal characteristics, the necessity of
      broad-scale measures for their conservation notwithstanding.

PMID- 28767104
TI  - Genomic signatures of paleodrainages in a freshwater fish along the southeastern
      coast of Brazil: genetic structure reflects past riverine properties.
AB  - Past shifts in connectivity in riverine environments (for example, sea-level
      changes) and the properties of current drainages can act as drivers of genetic
      structure and demographic processes in riverine population of fishes. However, it
      is unclear whether the same river properties that structure variation on recent
      timescales will also leave similar genomic signatures that reflect paleodrainage
      properties. By characterizing genetic structure in a freshwater fish species
      (Hollandichthys multifasciatus) from a system of basins along the Atlantic coast
      of Brazil we test for the effects of paleodrainages caused by sea-level changes
      during the Pleistocene. Given that the paleodrainage properties differ along the
      Brazilian coast, we also evaluate whether estimated genetic diversity within
      paleodrainages can be explained by past riverine properties (i.e., area and
      number of rivers in a paleodrainage). Our results demonstrate that genetic
      structure between populations is not just highly concordant with paleodrainages,
      but that differences in the genetic diversity among paleodrainages correspond to
      the joint effect of differences in the area encompassed by, and the number of
      rivers, within a paleodrainage. Our findings extend the influence of current
      riverine properties on genetic diversity to those associated with past
      paleodrainage properties. We discuss how these findings may explain the
      inconsistent support for paleodrainages in structuring divergence from different
      global regions and the importance of taking into account past conditions for
      understanding the high species diversity of freshwater fish that we currently
      observe in the world, and especially in the Neotropics.

PMID- 28767106
TI  - Opioid abuse in children: an emerging public health crisis in the United States!

PMID- 28767107
TI  - An organometallic route to chiroptically active ZnO nanocrystals.
AB  - The unique optical properties of zinc oxide nanocrystals (ZnO NCs) are strongly
      dependent on both the properties and the composition of the inorganic core
      organic ligand interface. Developing a novel organometallic self-supporting
      approach, we report on the synthesis and characterization of ZnO nanocrystals
      coated by chiral monoanionic aminoalcoholate ligands. The resulting ZnO NCs are
      both chiroptically active and possess size dependent optical properties. The size
      and in consequence the emission color of the ZnO NCs could be simply adjusted by
      the characteristic of the aminoalcohol used.

PMID- 28767108
TI  - Bioorganometallic ferrocene-tripeptide nanoemulsions.
AB  - We demonstrate an effective strategy to prepare highly stable nanoemulsions using
      ferrocene-modified tripeptides. Compared with traditional nanoemulsions,
      bioorganometallic peptide nanoemulsions are appealing for a number of reasons,
      including long-term and outstanding thermal stability, redox activity and
      biocompatibility. The formed nanoemulsions could remain stable for more than four
      months at room temperature, which is the highest stability reported so far for
      peptide and protein emulsifiers. The phase behaviour and size distribution of the
      emulsions could be precisely tailored by altering the temperature, solvent ratio
      and redox state of the ferrocene moiety. In this process, we observed a unique
      enthalpy-driven phase transition from nanoemulsions to hydrogels, which could be
      attributed to the competition between the interfacial free energy and the
      association energy among the self-assembling peptides. Moreover, we could impart
      catalytic activity to the nanoemulsions through rationally altering the sequence
      of the tripeptides. The structurally tunable, functional bioorganometallic
      nanoemulsions offer new opportunities in many areas including drug delivery, and
      the food and cosmetic industries.

PMID- 28767105
TI  - Erratum: Genetic loci associated with heart rate variability and their effects on
      cardiac disease risk.
AB  - This corrects the article DOI: 10.1038/ncomms15805.

PMID- 28767109
TI  - Ionic selectivity and filtration from fragmented dehydration in multilayer
      graphene nanopores.
AB  - Selective ion transport is a hallmark of biological ion channel behavior but is a
      major challenge to engineer into artificial membranes. Here, we demonstrate, with
      all-atom molecular dynamics simulations, that bare graphene nanopores yield
      measurable ion selectivity that varies over one to two orders of magnitude simply
      by changing the pore radius and number of graphene layers. Monolayer graphene
      does not display dehydration-induced selectivity until the pore radius is small
      enough to exclude the first hydration layer from inside the pore. Bi- and tri
      layer graphene, though, display such selectivity already for a pore size that
      barely encroaches on the first hydration layer, which is due to the more
      significant water loss from the second hydration layer. Measurement of
      selectivity and activation barriers from both first and second hydration layer
      barriers will help elucidate the behavior of biological ion channels. Moreover,
      the energy barriers responsible for selectivity - while small on the scale of
      hydration energies - are already relatively large, i.e., many kBT. For separation
      of ions from water, therefore, one can exchange longer, larger radius pores for
      shorter, smaller radius pores, giving a practical method for maintaining
      exclusion efficiency while enhancing other properties (e.g., water throughput).

PMID- 28767111
TI  - A novel strategy to immobilize bacteria on polymer particles for efficient
      adsorption and biodegradation of soluble organics.
AB  - A novel strategy was used to immobilize bacterial cells on the surface of
      functional polymer particles for the efficient adsorption and biodegradation of
      organics in wastewater. First, the bacterial cells were aggregated using a vinyl
      containing pre-polymer, and the obtained bacteria-pre-polymer complex was then
      used as a particle stabilizer to construct a stable Pickering emulsion of
      functional cross-linking monomers and hydrophobic superparamagnetic iron oxide
      nanoparticles (the oil phase) in water. After polymerization, the bacteria-pre
      polymer complex was covalently fixed to the surface of the polymer particles. Two
      species of bacterial cells (Pseudomonas putida andParacoccus denitrificans) were
      used as models to study their removal capacity for phenol and DMF, respectively.
      Batch experiments showed that the as-prepared magnetic bacteria-polymer (MPB)
      composites could efficiently remove organics from the aqueous solutions, and the
      encapsulated iron oxide nanoparticles enabled the MPB composites to be
      magnetically separated.

PMID- 28767112
TI  - Chemical-doping-driven crossover from graphene to "ordinary metal" in epitaxial
      graphene grown on SiC.
AB  - Atmospheric chemical doping can be used to modify the electronic properties of
      graphene. Here we report that the chemical atmospheric doping (derived from air,
      oxygen and water vapor) of low-carrier-density monolayer epitaxial graphene on
      SiC can be readily tuned by a simple low-temperature (T <= 450 K), in situ vacuum
      gentle heating method. Interestingly, such an approach allows, for the first
      time, the observation of a crossover from graphene (MUt/MUq ~ 2) to an "ordinary
      metal" (MUt/MUq ~ 1) with decreasing carrier density, where MUt and MUq are
      transport mobility and quantum mobility, respectively. In the low carrier density
      limit, our results are consistent with the theoretical prediction that MUt is
      inversely proportional to charged impurity density. Our data also suggest that
      atmospheric chemical doping can be used to vary intervalley scattering in
      graphene which plays a crucial role in backward scattering events.

PMID- 28767110
TI  - Microfluidic platform for efficient Nanodisc assembly, membrane protein
      incorporation, and purification.
AB  - The characterization of integral membrane proteins presents numerous analytical
      challenges on account of their poor activity under non-native conditions, limited
      solubility in aqueous solutions, and low expression in most cell culture systems.
      Nanodiscs are synthetic model membrane constructs that offer many advantages for
      studying membrane protein function by offering a native-like phospholipid bilayer
      environment. The successful incorporation of membrane proteins within Nanodiscs
      requires experimental optimization of conditions. Standard protocols for Nanodisc
      formation can require large amounts of time and input material, limiting the
      facile screening of formation conditions. Capitalizing on the miniaturization and
      efficient mass transport inherent to microfluidics, we have developed a
      microfluidic platform for efficient Nanodisc assembly and purification, and
      demonstrated the ability to incorporate functional membrane proteins into the
      resulting Nanodiscs. In addition to working with reduced sample volumes, this
      platform simplifies membrane protein incorporation from a multi-stage protocol
      requiring several hours or days into a single platform that outputs purified
      Nanodiscs in less than one hour. To demonstrate the utility of this platform, we
      incorporated Cytochrome P450 into Nanodiscs of variable size and lipid
      composition, and present spectroscopic evidence for the functional active site of
      the membrane protein. This platform is a promising new tool for membrane protein
      biology and biochemistry that enables tremendous versatility for optimizing the
      incorporation of membrane proteins using microfluidic gradients to screen across
      diverse formation conditions.

PMID- 28767113
TI  - Tunable AIEE fluorescence constructed from a triphenylamine luminogen containing
      quinoline - application in a reversible and tunable pH sensor.
AB  - Herein, tunable emissions in aggregation processes of triphenylamine derivatives
      (TPAQs) and their protonated cations, as well as protonated processes have been
      described. In this study, three triphenylamine-based compounds (TPAQs) were
      synthesized and their optical properties were investigated. Initially, the TPAQs
      displayed aggregation-induced emission enhancement (AIEE) properties via the
      restricted intramolecular charge transfer (ICT) state. Interestingly, the single
      branched fluorophore (STPAQ) and its protonated cation emitted different color
      fluorescence in the solution and aggregation state. They emitted green
      fluorescence, which originated from the intramolecular charge transfer (ICT)
      state in a strong polar solvent, but the fluorescence bands turned blue, which
      was attributed to the LE state in the aggregated state. However, the cations of
      triple-branched fluorophores (TTPAQs) exhibited an inverse tunable emission
      process from bluish violet fluorescence of the LE state in a weak polar solvent
      (e.g., THF) to green fluorescence of the ICT state in the aggregated state. In a
      THF/water mixture solution (fw = 10%), the STPAQ could switch its emission
      between blue and green in the pH range of 10.0-0.5. This phenomenon enabled STPAQ
      to serve as a fluorescent pH sensor in solution. In the powder state, double
      branched fluorophores (DTPAQs) could be used as a fluorescent sensor for the
      detection of acidic and basic organic vapors in the solid state.

PMID- 28767114
TI  - In situ twisting for stabilizing and toughening conductive graphene yarns.
AB  - Graphene fibres are of great interest for diverse applications such as their use
      in supercapacitors, batteries, stimulus-responsive actuators and smart textiles.
      However, previously reported graphene-based fibres commonly have very low
      toughness and poor stretchability, which can limit many of their possible
      applications. We demonstrate an efficient approach for preparing super-tough
      yarns of reduced graphene oxides via the in situ twisting of multiplied graphene
      oxide fibres during fibre extrusion and coagulation, followed by chemical
      reduction and drying. These twisted multiplied yarns have a toughness of 46.3 J m
      3, much higher than previous results for graphene-based fibres and films, and
      benefit from the retention of high strength and a significant increase in the
      failure strain due to the stably twisted hollow structure of the yarns. These
      yarns also show very stable electrical resistance when subjected to cyclic
      stretching at a large tensile strain. We demonstrate the utilization of such
      yarns for stretchable conducting electronic wires.

PMID- 28767115
TI  - Solvent diffusion in polymer-embedded hollow nanoparticles studied by in situ
      small angle X-ray scattering.
AB  - In situ time-resolved small-angle X-ray scattering is introduced as a method to
      monitor the diffusion of a solvent in ceramic hollow nanoparticles (HNPs)
      supported by a polymer gel scaffold. Changes in the form factor were matched to
      discrete scattering models. A consecutive reaction kinetic model is used to
      analyze different stages of solvent diffusion. Rate constants and diffusion
      coefficients are extracted. By taking the diffusion of low molecular
      poly(ethylene glycol) in poly(ethylene oxide)-embedded HNPs as a model case, it
      was found that it took about 0.7 s for the solvent to diffuse through the 6 nm
      thick shell of HNPs and another 1.2 s to fill the inner cavity, while the
      diffusion coefficient was of the order of 1018 m2 s-1. The results demonstrate
      that the method can simultaneously measure solvent penetration into the polymer
      gel and into embedded sub-100 nm HNPs.

PMID- 28767116
TI  - A surprising way to control the charge transport in molecular electronics: the
      subtle impact of the coverage of self-assembled monolayers of floppy molecules
      adsorbed on metallic electrodes.
AB  - Inspired by earlier attempts in organic electronics aiming at controlling charge
      injection from metals into organic materials by manipulating the Schottky energy
      barrier using self-assembled monolayers (SAMs), recent experimental and
      theoretical work in molecular electronics showed that metal-organic interfaces
      can be controlled via changes in the metal work function that are induced by
      SAMs. In this paper we indicate a different route to achieve interface-driven
      control over the charge transfer/transport at the molecular scale. It is based on
      the fact that, in floppy molecule based SAMs, the molecular conformation can be
      tuned by varying the coverage of the adsorbate. We demonstrate this effect with
      the aid of benchmark molecules that are often used to fabricate nanojunctions and
      consist of two rings that can easily rotate relative to each other. We show that,
      by varying the coverage of the SAM, the twisting angle phi of the considered
      molecular species can be modified by a factor of two. Given the fact that the low
      bias conductance G scales as cos2 phi, this results in a change in G of over one
      order of magnitude for the considered molecular species. Tuning the twisting
      angle by controlling the SAM coverage may be significant, e.g., for current
      efforts to fabricate molecular switches. Conversely, the lack of control over the
      local SAM coverage may be problematic for the reproducibility and interpretation
      of the STM (scanning tunneling microscope) measurements on repeatedly forming
      single molecule break junctions.

PMID- 28767120
TI  - Self-assembly of an amphipathic alphaalphabeta-tripeptide into cationic spherical
      particles for intracellular delivery.
AB  - The development of molecular carriers able to carry molecules directly into the
      cell is an area of intensive research. Cationic nanoparticles are effective
      delivery systems for several classes of molecules, such as anticancer agents,
      oligonucleotides and antibodies. Indeed, a cationic charge on the outer surface
      allows a rapid cellular uptake together with the possibility of carrying
      negatively charged molecules. In this work, we studied the self-assembly of an
      ultra-short alphaalphabeta-tripeptide containing an l-Arg-l-Ala sequence and an
      unnatural fluorine substituted beta2,3-diaryl-amino acid. The presence of the
      unnatural beta2,3-diaryl-amino acid allowed us to obtain a protease stable
      sequence. Furthermore, an arginine guanidinium group triggered the formation of
      spherical assemblies that were able to load small molecules and enter cells.
      These spherical architectures, thus, represent interesting candidates for the
      delivery of exogenous entities directly into cells.

PMID- 28767121
TI  - Combined association of Presenilin-1 and Apolipoprotein E polymorphisms with
      maternal meiosis II error in Down syndrome births.
AB  - Alzheimer's disease and Down syndrome often exhibit close association and
      predictively share common genetic risk-factors. Presenilin-1 (PSEN-1) and
      Apolipoprotein E (APOE) genes are associated with early and late onset of
      Alzheimer's disease, respectively. Presenilin -1 is involved in faithful
      chromosomal segregation. A higher frequency of the APOE epsilon4 allele has been
      reported among young mothers giving birth to Down syndrome children. In this
      study, 170 Down syndrome patients, grouped according to maternal meiotic stage of
      nondisjunction and maternal age at conception, and their parents were genotyped
      for PSEN-1 intron-8 and APOE polymorphisms. The control group consisted of 186
      mothers of karyotypically normal children. The frequencies of the PSEN-1 T allele
      and TT genotype, in the presence of the APOE epsilon4 allele, were significantly
      higher among young mothers (< 35 years) with meiosis II nondisjunction than in
      young control mothers (96.43% vs. 65.91% P = 0.0002 and 92.86% vs. 45.45% P <
      0.0001 respectively) but not among mothers with meiosis I nondisjunction. We
      infer that the co-occurrence of the PSEN-1 T allele and the APOE epsilon4 allele
      associatively increases the risk of meiotic segregation error II among young
      women.

PMID- 28767122
TI  - Bradyrhizobium elkanii nod regulon: insights through genomic analysis.
AB  - A successful symbiotic relationship between soybean [Glycine max (L.) Merr.] and
      Bradyrhizobium species requires expression of the bacterial structural nod genes
      that encode for the synthesis of lipochitooligosaccharide nodulation signal
      molecules, known as Nod factors (NFs). Bradyrhizobium diazoefficiens USDA 110
      possesses a wide nodulation gene repertoire that allows NF assembly and
      modification, with transcription of the nodYABCSUIJnolMNOnodZ operon depending
      upon specific activators, i.e., products of regulatory nod genes that are
      responsive to signaling molecules such as flavonoid compounds exuded by host
      plant roots. Central to this regulatory circuit of nod gene expression are NodD
      proteins, members of the LysR-type regulator family. In this study, publicly
      available Bradyrhizobium elkanii sequenced genomes were compared with the closely
      related B. diazoefficiens USDA 110 reference genome to determine the similarities
      between those genomes, especially with regards to the nod operon and nod regulon.
      Bioinformatics analyses revealed a correlation between functional mechanisms and
      key elements that play an essential role in the regulation of nod gene
      expression. These analyses also revealed new genomic features that had not been
      clearly explored before, some of which were unique for some B. elkanii genomes.

PMID- 28767123
TI  - Complete mitochondrial genome of the lappet moth, Kunugia undans (Lepidoptera:
      Lasiocampidae): genomic comparisons among macroheteroceran superfamilies.
AB  - The mitochondrial genome (mitogenome) characteristics of the monotypic
      Lasiocampoidea are largely unknown, because only limited number of mitogenomes is
      available from this superfamily. In this study, we sequenced the complete
      mitogenome of the lappet moth, Kunugia undans (Lepidoptera: Lasiocampidae) and
      compared it to those of Lasiocampoidea and macroheteroceran superfamilies (59
      species in six superfamilies). The 15,570-bp K. undans genome had one additional
      trnR that was located between trnA and trnN loci and this feature was unique in
      Macroheterocera, including Lasiocampoidea. Considering that the two trnR copies
      are located in tandem with proper secondary structures and identical anticodons,
      a gene duplication event might be responsible for the presence of the two tRNAs.
      Nearly all macroheteroceran species, excluding Lasiocampoidea, have a spacer
      sequence (1-34 bp) at the trnS2 and ND1 junction, but most lasiocampid species,
      including K. undans, have an overlap at the trnS2 and ND1 junction, which
      represents a different genomic feature in Lasiocampoidea. Nevertheless, a TTAGTAT
      motif, which is typically detected in Macroheterocera at the trnS2 and ND1
      junction, was also detected in all Lasiocampoidea. In summary, the general
      mitogenome characteristics of Lasiocampoidea did not differ greatly from the
      remaining macroheteroceran superfamilies, but it did exhibit some unique
      features.

PMID- 28767124
TI  - The prognosis for prognostic tools.

PMID- 28767126
TI  - Photocrosslinking of Polyglycidol and Its Derivative: Route to Thermoresponsive
      Hydrogels.
AB  - Hydrogels of biologically well-tolerated, high-molar-mass polyglycidol (PGl) and
      its thermoresponsive derivative poly(glycidol-co-ethyl glycidyl carbamate) have
      been obtained by direct UV crosslinking in the solid state. Polymers with molar
      masses up to 1.45 * 106 g mol-1 were crosslinked in the presence of benzophenone
      or (4-benzoylbenzyl)trimethylammonium chloride as photosensitizers. The
      photosensitizer concentration was varied from 2 to 10 wt%. The influence of
      polymer composition and photosensitizer type and amount on the crosslinking
      efficiency, swelling and temperature behavior of the obtained hydrogels was
      investigated. The photocrosslinking of PGl and poly(glycidol-co-ethyl glycidyl
      carbamate) led to hydrogels with swelling degrees up to 1700%. The swelling
      degrees of the hydrogels decreased with the increase of the environmental
      temperature indicating the thermoresponsive nature of gels. The swelling of
      obtained gels can be controlled by varying the composition of the copolymer
      precursor and by the network density.

PMID- 28767125
TI  - ERAS: Improving outcome in the cachectic HPB patient.
AB  - The enhanced recovery after surgery (ERAS) program has reduced postoperative
      morbidity and duration of hospital stay but not mortality in patients undergoing
      hepatopancreatobiliary (HPB) surgery. Many HPB patients suffer from cancer
      cachexia, a syndrome of severe weight and muscle loss. This may affect outcomes
      of HPB surgery even within an ERAS program. A tailored ERAS approach may be
      essential in further improving outcome in this vulnerable patient category.

PMID- 28767127
TI  - Social functioning in patients with depressive and anxiety disorders.
AB  - OBJECTIVE: Adaptive social functioning is severely impeded in depressive and
      anxiety disorders, even after remission. However, a comprehensive overview is
      still lacking. METHOD: Using data from the Netherlands Study of Depression and
      Anxiety (NESDA), behavioural (network size, social activities, social support)
      and affective (loneliness, affiliation, perceived social disability) indicators
      of social functioning were analyzed in patients with anxiety (N = 540),
      depressive (N = 393), comorbid anxiety and depressive disorders ('comorbid', N =
      748), remitted participants (N = 621), and healthy control subjects (N = 650).
      RESULTS: Analyses revealed an increasing trend of social dysfunction among
      patient groups, in patients with comorbid anxiety and depressive disorders,
      showing the most severe impairments, followed by depressed and anxious patients
      (P's < 0.001 for all social functioning indicators). Affective indicators showed
      the largest effect sizes (Cohen's d range from 0.13 to 1.76). We also found
      impairments in social functioning among remitted patients. Furthermore, perceived
      social disability among patients was predictive of still having a depressive
      and/or anxiety diagnosis 2 years later (P < 0.01). CONCLUSIONS: Behavioural but
      especially affective indicators of social functioning are impaired in patients
      with anxiety or depressive disorders and most in patients with comorbid
      disorders. After remission of affective psychopathology, residual impairments
      tend to remain, while social dysfunction in patients seems predictive of future
      psychopathology.

PMID- 28767128
TI  - Inter- and intraspecific variability in physiological traits and post-anoxia
      recovery of photosynthetic efficiency in grasses under oxygen deprivation.
AB  - Low oxygen conditions occur in grass sites due to high and frequent
      precipitation, poor soil quality, and over-irrigation followed by slow drainage.
      Three warm-season and one cool-season grass were analyzed at metabolic level
      during a time-course experiment performed in a controlled anoxic environment.
      Prolonged oxygen depletion proved detrimental by leading to premature death to
      all the species, with the exception of seashore paspalum. Moreover, the anoxia
      tolerance observed in these grasses has been associated with slow use of
      carbohydrates, rather than with their relative abundance, which was more
      important than their antioxidant capacity. Further physiological characterization
      of eight seashore paspalum genotypes to anoxia was also performed, by examining
      the variation in photosystem II (PSII) efficiency and gas exchange during post
      anoxia recovery. Multivariate analysis highlighted the presence of three main
      clusters of seashore paspalum genotypes, characterized by different ability to
      restore the PSII photochemistry during recovery after one day of anoxia. Taken
      together, our data demonstrate that the analysis of post-anoxia recovery of
      fluorescence and gas exchange parameters can represent a fast and reliable
      indicator for selecting species and cultivars more able to acclimate their
      photosynthetic apparatus.

PMID- 28767129
TI  - The role of Euglena gracilis paramylon in modulating xylem hormone levels,
      photosynthesis and water-use efficiency in Solanum lycopersicum L.
AB  - beta-1,3-glucans such as paramylon act as elicitors in plants, modifying the
      hormonal levels and the physiological responses. Plant hormones affect all phases
      of the plant life cycle and their responses to environmental stresses, both
      biotic and abiotic. The aim of this study was to investigate the effects of a
      root treatment with Euglena gracilis paramylon on xylem hormonal levels,
      photosynthetic performance and dehydration stress in tomato (Solanum
      lycopersicum). Paramylon granules were processed to obtain the linear fibrous
      structures capable to interact with tomato cell membrane. Modulation of hormone
      levels (abscisic acid, jasmonic acid and salicylic acid) and related
      physiological responses such as CO2 assimilation rate, stomatal and mesophyll
      conductance, intercellular CO2 concentration, transpiration rate, water-use
      efficiency, quantum yield of photosystem II and leaf water potential were
      investigated. The results indicate a clear dose-dependent effect of paramylon on
      the hormonal content of xylem sap, photosynthetic performance and dehydration
      tolerance. Paramylon has the capability to enhance plant defense capacity against
      abiotic stress, such as drought, by modulating the conductance to CO2 diffusion
      from air to the carboxylation sites and improving the water-use efficiency.

PMID- 28767130
TI  - Tumour-associated microglia/macrophages predict poor prognosis in high-grade
      gliomas and correlate with an aggressive tumour subtype.
AB  - AIMS: Glioblastomas are highly aggressive and treatment resistant. Increasing
      evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate
      tumour progression by acquiring a M2-like phenotype. Our objective was to
      investigate the prognostic value of TAMs in gliomas using automated quantitative
      double immunofluorescence. METHODS: Samples from 240 patients with primary glioma
      were stained with antibodies against ionized calcium-binding adaptor molecule-1
      (IBA-1) and cluster of differentiation 204 (CD204) to detect TAMs and M2-like
      TAMs. The expression levels were quantified by software-based classifiers. The
      associations between TAMs, gemistocytic cells and glioblastoma subtype were
      examined with immuno- and haematoxylin-eosin stainings. Three tissue arrays
      containing glioblastoma specimens were included to study IBA-1/CD204 levels in
      central tumour and tumour periphery and to characterize CD204+ cells. RESULTS:
      Our data revealed that the amount of especially CD204+ TAMs increases with
      malignancy grade. In grade III-IV, high CD204 expression was associated with
      shorter survival, while high IBA-1 intensity correlated with a longer survival.
      In grade IV, CD204 showed independent prognostic value when adjusting for
      clinical data and the methylation status of O6-methylguanine-DNA
      methyltransferase. Our findings were confirmed in two bioinformatics databases.
      TAMs were more abundant in central tumour tissue, mesenchymal glioblastomas and
      gliomas with many gemistocytic cells. CD204+ TAMs co-expressed proteins related
      to tumour aggressiveness including matrix metallopeptidase-14 and hypoxia
      inducible factor-1alpha. CONCLUSIONS: This is the first study to use automated
      quantitative immunofluorescence to determine the prognostic impact of TAMs. Our
      results suggest that M2-like TAMs hold an unfavourable prognostic value in high
      grade gliomas and may contribute to a pro-tumourigenic microenvironment.

PMID- 28767131
TI  - A prognostic mutation panel for predicting cancer recurrence in stages II and III
      colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Approximately 20-40% of stage II/III colorectal cancer
      (CRC) patients develop relapse. Clinicopathological factors alone are limited in
      detecting these patients, resulting in potential under/over-treatment. We sought
      to identify a prognostic tumor mutational profile that could predict CRC
      recurrence. METHODS: Whole-exome sequencing data were obtained for 207 patients
      with stage II/III CRC from The Cancer Genome Atlas. Mutational landscape in
      relapse-free versus relapsed cohort was compared using Fisher's exact test,
      followed by multivariate Cox regression to identify genes associated with cancer
      recurrence. Bootstrap-validation was used to examine internal/external validity.
      RESULTS: We identified five prognostic genes (APAF1, DIAPH2, NTNG1, USP7, and
      VAV2), which were combined to form a prognostic mutation panel. Patients with >=1
      mutation(s) within this five-gene panel had worse prognosis (3-yr relapse-free
      survival [RFS]: 53.0%), compared to patients with no mutation (3-yr RFS: 84.3%).
      In multivariate analysis, the five-gene panel remained prognostic for cancer
      recurrence independent of stage and high-risk features (hazard ratio 3.63, 95%CI
      [1.93-6.83], P < 0.0001). Furthermore, its prognostic accuracy was superior to
      the American Joint Commission on Cancer classification (concordance-index: 0.70
      vs 0.54). CONCLUSIONS: Our proposed mutation panel identifies CRC patients at
      high-risk for recurrence, which may help guide adjuvant therapy and post
      operative surveillance protocols.

PMID- 28767132
TI  - Antenatal Corticosteroid Prophylaxis in Singleton and Multiple Pregnancies.
AB  - BACKGROUND: The effects of antenatal corticosteroids (ANS) in multiple
      pregnancies are disputed. In this article, we examined whether estimated effects
      differ in singletons and multiples and in small for gestational age (SGA) preterm
      infants. METHODS: We studied 17 073 singletons (81% treated with ANS) and 8274
      multiples (86% treated) born at 24-33 weeks from the Italian Neonatal Network
      (2005-2013). We used Poisson regression models with robust variance to estimate
      adjusted risk ratios (RR) of in-hospital death, severe intraventricular
      haemorrhage (IVH), periventricular leukomalacia (PVL), and the composite outcome
      of severe IVH and death. RESULTS: Mortality was lower among ANS-treated vs. ANS
      untreated infants, both in singletons (RR 0.63, 95% confidence interval (CI)
      0.58, 0.68) and in multiples (RR 0.85, 95% CI 0.73, 0.98). IVH and the composite
      outcome of IVH and death, but not PVL, also occurred less frequently among ANS
      treated infants. For these outcomes, the effect of ANS was stronger in singletons
      than in multiples (+35%, +32%, and +22% for death, IVH, and the composite
      outcome, respectively). Also among SGA infants, singletons, and multiples, ANS
      treated infants had lower risk of death, IVH and of composite outcome than
      untreated ones. CONCLUSIONS: In this large cohort of preterm infants, both
      multiples and singletons treated with ANS had a lower risk of mortality, of
      severe IVH, and of composite outcome of IVH and death, both in the overall sample
      and in SGA infants. Although ANS effect was weaker in multiples, our results
      support current recommendations to administer ANS prophylaxis in multiple
      pregnancies at risk of preterm delivery.

PMID- 28767133
TI  - Cutinsomes as building-blocks of Arabidopsis thaliana embryo cuticle.
AB  - Cutinsomes, spherical nanoparticles containing cutin mono- and oligomers, are
      engaged in cuticle formation. Earlier they were revealed to participate in
      cuticle biosynthesis in Solanum lycopersicum fruit and Ornithogalum umbellatum
      ovary epidermis. Here, transmission electron microscopy (TEM) and immunogold
      labeling with antibody against the cutinsomes were applied to aerial cotyledon
      epidermal cells of Arabidopsis thaliana mature embryos. TEM as well as gold
      particles conjugated with the cutinsome antibody revealed these structures in the
      cytoplasm, near the plasmalemma, in the cell wall and incorporated into the
      cuticle. Thus, the cutinsomes most probably are involved in the formation of A.
      thaliana embryo cuticle and this model plant is another species in which these
      specific structures participate in the building of cuticle in spite of the lack
      of the lipotubuloid metabolon. In addition, a mechanism of plant cuticle lipid
      biosynthesis based on current knowledge is proposed.

PMID- 28767134
TI  - Differential impact of amino acids on OXPHOS system activity following
      carbohydrate starvation in Arabidopsis cell suspensions.
AB  - Plant respiration mostly depends on the activity of glycolysis and the oxidation
      of organic acids in the tricarboxylic acid cycle to synthesize ATP. However,
      during stress situations plant cells also use amino acids as alternative
      substrates to donate electrons through the electron-transfer flavoprotein
      (ETF)/ETF:ubiquinone oxidoreductase (ETF/ETFQO) complex to the mitochondrial
      electron transport chain (mETC). Given this, we investigated changes of the
      oxidative phosphorylation (OXPHOS) system in Arabidopsis thaliana cell culture
      under carbohydrate starvation supplied with a range of amino acids. Induction of
      isovaleryl-CoA dehydrogenase (IVDH) activity was observed under carbohydrate
      starvation which was associated with increased amounts of IVDH protein detected
      by immunoblotting. Furthermore, activities of the protein complexes of the mETC
      were reduced under carbohydrate starvation. We also observed that OXPHOS system
      activity behavior is differently affected by different amino acids and that
      proteins associated with amino acids catabolism are upregulated in cells
      following carbohydrate starvation. Collectively, our results support the
      contention that ETF/ETFQO is an essential pathway to donate electrons to the mETC
      and that amino acids are alternative substrates to maintain respiration under
      carbohydrate starvation.

PMID- 28767136
TI  - Is There Any Hope? How Climate Change News Imagery and Text Influence Audience
      Emotions and Support for Climate Mitigation Policies.
AB  - Using a national sample, this study experimentally tests the effects of news
      visuals and texts that emphasize either the causes and impacts of climate change
      or actions that can be taken to address climate change. We test the effects of
      variations in text and imagery on discrete emotions (i.e., hope, fear, and anger)
      and, indirectly, on support for climate mitigation policies. Political ideology
      is examined as a moderator. The findings indicate that news images and texts that
      focus on climate-oriented actions can increase hope and, in the case of texts,
      decrease fear and anger, and these effects generally hold across the ideological
      spectrum. In turn, the influence of emotions on policy support depends on
      ideology: Hope and fear increase support for climate policies for all ideological
      groups but particularly conservatives, whereas anger polarizes the opinions of
      liberals and conservatives. Implications for climate change communication that
      appeals to emotions are discussed.

PMID- 28767135
TI  - Phenotypic outcomes in adolescence and adulthood in the scarcity-adversity model
      of low nesting resources outside the home cage.
AB  - Early life adversity is known to disrupt behavioral trajectories and many rodent
      models have been developed to characterize these stress-induced outcomes. One
      example is the scarcity-adversity model of low nesting resources. This model
      employs resource scarcity (i.e., low nesting materials) to elicit adverse
      caregiving conditions (including maltreatment) toward rodent neonates. Our lab
      utilizes a version of this model wherein caregiving exposures occur outside the
      home cage during the first postnatal week. The aim of this study was to determine
      adolescent and adult phenotypic outcomes associated with this model, including
      assessment of depressive- and anxiety-like behaviors and performance in different
      cognitive domains. Exposure to adverse caregiving had no effect on adolescent
      behavioral performance whereas exposure significantly impaired adult behavioral
      performance. Further, adult behavioral assays revealed substantial differences
      between sexes. Overall, data demonstrate the ability of repeated exposure to
      brief bouts of maltreatment outside the home cage in infancy to impact the
      development of several behavioral domains later in life.

PMID- 28767137
TI  - Change in HER2 status after neoadjuvant chemotherapy and the prognostic impact in
      patients with primary breast cancer.
AB  - BACKGROUND: We aimed to assess change in HER2 status after neoadjuvant
      chemotherapy (NAC) in patients with primary breast cancer and the prognostic
      impact of such changes. PATIENTS AND METHODS: The study comprised 588 patients
      with a non-pathologic complete response who received anthracycline and/or taxane
      based regimens in NAC setting. HER2 status was assessed before NAC and in
      residual invasive tumor of the surgical specimens. The associations between the
      change in HER2 status and clinicopathological factors were assessed. RESULTS:
      Before NAC, 489 (83%) of the 588 patients had HER2-negative tumors and 99
      patients (17%) had HER2-positive tumors. Eleven (2.2%) of the HER2-negative
      tumors changed to HER2-positive, while 33 (33%) of the HER2-positive tumors
      changed to HER2-negative. ER and PR-positivity before NAC were associated with
      loss of HER2-positivity, whereas receiving trastuzumab was not. In terms of
      disease-free survival, there was no difference between patients with and those
      without change in HER2 status after NAC in either the patients with HER2-negative
      tumors (P = 0.26) or with HER2-positive tumors before NAC (P = 0.23). CONCLUSION:
      Our results showed that changes in HER2 status did not affect patients'
      prognosis. Further studies are needed to determine whether HER2-targeting agents
      can be omitted when loss of HER2-positivity is confirmed after NAC.

PMID- 28767138
TI  - Birth Defect Outcomes in Pregnancies Conceived through In Vitro Fertilisation.

PMID- 28767140
TI  - Comparative proteomic analysis provides novel insights into chlorophyll
      biosynthesis in celery under temperature stress.
AB  - Chlorophyll (Chl) is essential for light harvesting and energy transduction in
      photosynthesis. A proper amount of Chl within plant cells is important to celery
      (Apium graveolens) yield and quality. Temperature stress is an influential
      abiotic stress affecting Chl biosynthesis and plant growth. There are limited
      proteomic studies regarding Chl accumulation under temperature stress in celery
      leaves. Here, the proteins from celery leaves under different temperature
      treatments (4, 25 and 38 degrees C) were analyzed using a proteomic approach.
      There were 71 proteins identified through MALDI-TOF-TOF analysis. The relative
      abundance of proteins involved in carbohydrate and energy metabolism, protein
      metabolism, amino acid metabolism, antioxidant and polyamine biosynthesis were
      enhanced under cold stress. These temperature stress-responsive proteins may
      establish a new homeostasis to enhance temperature tolerance. Magnesium chelatase
      (Mg-chelatase) and glutamate-1-semialdehyde aminotransferase (GSAT), related to
      Chl biosynthesis, showed increased abundances under cold stress. Meanwhile, the
      Chl contents were decreased in heat- and cold-stressed celery leaves. The
      inhibition of Chl biosynthesis may be due to the downregulated mRNA levels of 15
      genes involved in Chl biosynthesis. The study will expand our knowledge on Chl
      biosynthesis and the temperature tolerance mechanisms in celery leaves.

PMID- 28767139
TI  - Personalizing prognosis in colorectal cancer: A systematic review of the quality
      and nature of clinical prognostic tools for survival outcomes.
AB  - Integrating diverse types of prognostic information into accurate, individualized
      estimates of outcome in colorectal cancer is challenging. Significant
      heterogeneity in colorectal cancer prognostication tool quality exists.
      Methodology is incompletely or inadequately reported. Evaluations of the internal
      or external validity of the prognostic model are rarely performed.
      Prognostication tools are important devices for patient management, but tool
      reliability is compromised by poor quality. Guidance for future development of
      prognostication tools in colorectal cancer is needed.

PMID- 28767141
TI  - Are Transplant Recipients Human Subjects When Research Is Conducted on Organ
      Donors?
AB  - Interventional research on deceased organ donors and donor organs prior to
      transplant holds the promise of reducing the number of patients who die waiting
      for an organ by expanding the pool of transplantable organs and improving
      transplant outcomes. However, one of the key challenges researchers face is an
      assumption that someone who receives an organ that was part of an interventional
      research protocol is always a human subject of that same study. The consequences
      of this assumption include the need for oversight by an institutional review
      board and for research-level informed consent from transplant recipients, all
      within the complex practical realities of the organ donation and transplantation
      process in the United States. The current national focus on this issue provides
      an opportunity to think critically about the policy goals of the human subjects
      regulations and their application to the nascent field of deceased organ donor
      intervention research. We propose that for donor research where the transplant
      recipient does not fall under the definition of human subject, the clinical
      consent model-rather than the consent model used for human research subjects-best
      facilitates the policy objectives of balancing clinical innovation, transparency,
      and protection of patients in an ethically responsible and legally compliant
      manner.

PMID- 28767142
TI  - Prognostic significance of tumor length in patients receiving esophagectomy for
      esophageal cancer.
AB  - AIMS: We investigated the prognostic value of tumor length measurements acquired
      both from pre-operative imaging and post-operative pathology in esophageal
      cancer. METHODS: Tumor lengths were examined retrospectively for 389
      esophagectomy patients with respect to Endoscopy, EUS (Endoscopic Ultrasound), CT
      and PET-CT, and pathology. Correlations between the measurements on the different
      approaches were assessed, and associations between tumor length and survival were
      analyzed. RESULTS: Only the tumor lengths assessed on pathology were found to be
      significantly associated with overall (P = 0.001) and recurrence free (P < 0.001)
      survival on univariable analysis. The median overall survival was 47.1 months in
      those patients with tumor lengths <3.0 cm, falling to 19.6 and 18.0 months in
      those with 3.0-4.4 and 4.5+ cm tumors, respectively, demonstrating a reduction in
      patient survival at a tumor length of around 3 cm. Tumor length on pathology was
      significantly correlated with tumor differentiation and both T- and N-categories.
      After accounting for these factors, tumor length on pathology was a significant
      independent predictor of recurrence-free (P = 0.016), but not overall (P = 0.128)
      survival. CONCLUSIONS: Tumor lengths on pathology were found to be the most
      predictive of patient outcome. However, after accounting for other tumor-related
      factors, tumor length only resulted in a marginal improvement in predictive
      accuracy.

PMID- 28767143
TI  - UVA-Induced DNA Damage and Apoptosis in Red Blood Cells of the African Catfish
      Clarias gariepinus.
AB  - Ultraviolet-A light (UVA)-induced DNA damage and repair in red blood cells to
      investigate the sensitivity of African catfish to UVA exposure is reported.
      Fishes were irradiated with various doses of UVA light (15, 30, and 60 min day-1
      for 3 days). Morphological and nuclear abnormalities in red blood cells were
      observed in the fish exposed to UVA compared with controls. Morphological
      alterations such as acanthocytes, crenated cells, swollen cells, teardrop-like
      cells, hemolyzed cells, and sickle cells were observed. Those alterations were
      increased after 24 h exposure to UVA light and decreased at 14 days after
      exposure. The percentage of apoptosis was higher in red blood cells exposed to
      higher doses of UVA light. No micronuclei were detected, but small nuclear
      abnormalities such as deformed and eccentric nuclei were observed in some groups.
      We concluded that exposure to UVA light induced DNA damage, apoptosis, and
      morphological alterations in red blood cells in catfish; however, catfish were
      found to be less sensitive to UVA light than wild-type medaka.

PMID- 28767144
TI  - Differences in Body Mass Index between Siblings Who Are Discordant for Exposure
      to Antenatal Maternal Smoking.
AB  - BACKGROUND: Maternal smoking during pregnancy is associated with increased
      childhood body mass index (BMI), but the relationship may be due to confounding
      by maternal factors. This study tested the hypothesis that siblings born to
      mothers who begin to smoke between pregnancies will have higher BMI than older
      unexposed siblings. METHODS: Maternal details from the Aberdeen Maternity and
      Neonatal Databank were linked to the Study of Trends in Obesity in North East
      Scotland which holds offspring BMI at 5 years of age. Change in maternal smoking
      status between pregnancies was linked to offspring BMI and also to the difference
      in BMI between siblings. RESULTS: Maternal smoking status in successive
      pregnancies was linked to child BMI at age 5 years in 6581 mother-child pairs of
      whom 718 included sibling pars. Children whose mothers had quit, started smoking
      or smoked in consecutive pregnancies had higher BMI compared with those not
      exposed to maternal smoking. Siblings born after onset of maternal smoking had
      higher mean BMI z score (0.19, 95% confidence interval (CI) 0.01, 0.36) compared
      with unexposed older siblings. Mean BMI z score was also higher by mean of 0.10
      (95% CI 0.01, 0.20) in younger sibling compared with older siblings born to
      mothers who smoked in both pregnancies. BMI z score was not significantly
      different between siblings whose mothers quit between pregnancies. CONCLUSIONS:
      In utero exposure to maternal smoking during pregnancy may increase the
      likelihood of increased BMI in childhood.

PMID- 28767145
TI  - A Two-Step Approach for Analysis of Nonignorable Missing Outcomes in Longitudinal
      Regression: an Application to Upstate KIDS Study.
AB  - BACKGROUND: Imperfect follow-up in longitudinal studies commonly leads to missing
      outcome data that can potentially bias the inference when the missingness is
      nonignorable; that is, the propensity of missingness depends on missing values in
      the data. In the Upstate KIDS Study, we seek to determine if the missingness of
      child development outcomes is nonignorable, and how a simple model assuming
      ignorable missingness would compare with more complicated models for a
      nonignorable mechanism. METHODS: To correct for nonignorable missingness, the
      shared random effects model (SREM) jointly models the outcome and the missing
      mechanism. However, the computational complexity and lack of software packages
      has limited its practical applications. This paper proposes a novel two-step
      approach to handle nonignorable missing outcomes in generalized linear mixed
      models. We first analyse the missing mechanism with a generalized linear mixed
      model and predict values of the random effects; then, the outcome model is fitted
      adjusting for the predicted random effects to account for heterogeneity in the
      missingness propensity. RESULTS: Extensive simulation studies suggest that the
      proposed method is a reliable approximation to SREM, with a much faster
      computation. The nonignorability of missing data in the Upstate KIDS Study is
      estimated to be mild to moderate, and the analyses using the two-step approach or
      SREM are similar to the model assuming ignorable missingness. CONCLUSIONS: The
      two-step approach is a computationally straightforward method that can be
      conducted as sensitivity analyses in longitudinal studies to examine violations
      to the ignorable missingness assumption and the implications relative to health
      outcomes.

PMID- 28767146
TI  - A Randomized Trial of Effects of Alcohol on Cytochrome P450 Eicosanoids,
      Mediators of Inflammation Resolution, and Blood Pressure in Men.
AB  - BACKGROUND: Cardiovascular effects of alcohol consumption may be influenced by
      both pro- and anti-inflammatory mechanisms. We previously showed that chronic
      alcohol consumption increased blood pressure (BP), oxidative stress, and 20
      hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory
      eicosanoid synthesized by cytochrome P450 (CYP450) enzymes from arachidonic acid.
      This study in men examined the effect of consuming red wine (RW) on BP in
      relation to changes in 20-HETE, oxidative stress (F2 -isoprostanes), markers of
      inflammation, anti-inflammatory CYP450 epoxyeicosatrienoic acids (EETs), and
      specialized pro-resolving mediators of inflammation (SPMs) derived from
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). METHODS: Normotensive
      men (n = 22) were randomly allocated to drink RW (375 ml/d) or the equivalent
      volume of dealcoholized red wine (DRW) or water for 4 weeks in a 12-week, 3
      period crossover trial. BP, heart rate, 20-HETE, F2 -isoprostanes, and SPM were
      measured at baseline, 4, 8, and 12 weeks. RESULTS: Drinking RW increased BP (p <
      0.05), plasma and urinary 20-HETE (p < 0.05), plasma F2 -isoprostanes (p <
      0.0001), and the SPMs 18-hydroxyeicosapentaenoic acid (18-HEPE) from EPA, and
      resolvin D1 (RvD1) and 17R-resolvin D1 (17R-RvD1) from DHA (all p < 0.05)
      compared with DRW and water. EETs and high-sensitivity C-reactive protein were
      unaffected by RW. Plasma 18-HEPE was positively related to urinary 20-HETE (p <
      0.008) only after RW. CONCLUSIONS: This study has shown that men consuming
      moderate-to-high alcohol as RW for 4 weeks had increased BP, 20-HETE, and
      oxidative stress, as well as specific SPM that resolve inflammation. These
      paradoxical findings require further studies to determine whether alcohol
      stimulates different CYP450 enzymes and whether the findings can be replicated in
      females.

PMID- 28767148
TI  - Fatty acids in substitute formulas for cow's milk allergy.
AB  - BACKGROUND: The role of dietary fats in food-related allergic symptoms is
      increasingly being investigated, since the pivotal role of fat-derived
      inflammatory substances, e.g., leukotrienes, has been realized. The objective of
      this study was to describe the fatty acid composition of several commercially
      available infant formulas that are used as substitutes for adapted cow's milk
      formulas. METHODS: Samples of nine formulas (two soy, two extensively hydrolyzed
      casein, three extensively hydrolyzed whey, and two amino-acid-based formulas) and
      human milk as control were analyzed by gas chromatography. RESULTS: The quantity
      of fatty acids in the formulas was within the breast-milk range. The percentage
      of energy derived from fat was below the European Society for Pediatric
      Gastroenterology and Nutrition recommendations in two cases, but, in the others,
      it roughly met the recommendations. The percentage of energy derived from
      linoleic acid was as recommended in all but two cases, where it was higher than
      recommended. As indicated by a quality indicator, the linoleic to alpha-linolenic
      acid ratio, altogether four formulas were within either the recommendations or
      the analyzed breast-milk range. In three cases, it was 1.5-2.5 and in two cases 4
      5 times higher than recommended. CONCLUSIONS: There are recommendations for
      infant formulas to meet nutritional requirements of fat intake, and the analyzed
      formulas are in most cases within the suggested ranges. However, little is known
      of requirements in allergic or inflammatory conditions, and whether these
      described fatty acid compositions are pro- or anti-inflammatory.

PMID- 28767149
TI  - Onset of action of mometasone furoate nasal spray (NASONEX(r) ) in seasonal
      allergic rhinitis.
AB  - BACKGROUND: Mometasone furoate nasal spray (MFNS, NASONEX(r) ), is a new
      synthetic corticosteroid with considerable efficacy in the treatment of seasonal
      and perennial rhinitis and less than 0.1% systemic absorption. This study was
      designed to evaluate the time of onset of action of MFNS. The subjects were
      evaluated over the course of 2 weeks during the spring allergy season. METHODS:
      The effects of MFNS 200 MUg given once daily for 2 weeks were evaluated in a
      randomized, multicenter, double-blind, placebo-controlled study in 201 patients
      with seasonal allergic rhinitis. Clinically significant onset of action was
      assessed prospectively by special patient diary cards kept during the first 3
      days of treatment. RESULTS: By 12 h after initial dosage (the earliest
      evaluation), 28% of patients in the MFNS group experienced clinically significant
      relief, compared with 13% of those given placebo (P=0.01). Median time to at
      least moderate symptom relief in patients who received MFNS was 35.9 h, compared
      with more than 72 h in patients given placebo (P<0.01). By 72 h, 64% of the
      patients receiving MFNS experienced at least moderate relief, compared with 40%
      of those treated with placebo (P<0.01). Both patient and physician ratings of
      symptom severity, response to treatment, and overall condition of rhinitis
      indicated significant (P<0.01) superiority of MFNS over placebo. MFNS was well
      tolerated, with adverse events comparable to placebo. CONCLUSIONS: MFNS provided
      rapid onset of clinically significant symptom relief in patients with seasonal
      allergic rhinitis.

PMID- 28767147
TI  - Programmed death 1 is highly expressed on CD8+ CD57+ T cells in patients with
      stable multiple sclerosis and inhibits their cytotoxic response to Epstein-Barr
      virus.
AB  - Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in
      the central nervous system of patients with multiple sclerosis (MS) as a possible
      cause of disease. We have investigated the response of a subpopulation of
      effector CD8+ T cells to EBV in 36 healthy donors and in 35 patients with MS in
      active and inactive disease. We have measured the expression of markers of
      degranulation, the release of cytokines, cytotoxicity and the regulation of
      effector functions by inhibitory receptors, such as programmed death 1 (PD-1) and
      human inhibitor receptor immunoglobulin-like transcript 2 (ILT2). We demonstrate
      that polyfunctional cytotoxic CD8+ CD57+ T cells are able to kill EBV-infected
      cells in healthy donors. In contrast, an anergic exhaustion-like phenotype of
      CD8+ CD57+ T cells with high expression of PD-1 was observed in inactive patients
      with MS compared with active patients with MS or healthy donors. Detection of
      CD8+ CD57+ T cells in meningeal inflammatory infiltrates from post-mortem MS
      tissue confirmed the association of this cell phenotype with the disease
      pathological process. The overall results suggest that ineffective immune control
      of EBV in patietns with MS during remission may be one factor preceding and
      enabling the reactivation of the virus in the central nervous system and may
      cause exacerbation of the disease.

PMID- 28767150
TI  - Latex allergy in Saudi children with spina bifida.
AB  - BACKGROUND: Children with spina bifida (SB) are exposed to latex soon after birth
      during bladder catheterization, rectal disimpaction, and multiple surgical
      procedures. IgE-mediated latex-allergic reactions have been reported recently in
      these children. Our study was designed to assess the prevalence of allergic
      reactions to latex products in a group of Saudi Arabian children with SB in a
      tertiary care hospital. METHODS: Fifty-nine patients, aged 1-20 years, with SB
      were evaluated by a questionnaire on type of latex reactions; family and personal
      history of other allergic disorders, such as asthma, rhinitis, and urticaria;
      type and number of surgical procedures; and frequency of bladder catheterization
      and manipulation with latex materials. Confirmation of latex sensitivity was
      measured by skin prick test (SPT), CAP test, and latex skin challenge. RESULTS:
      Allergy to latex was detected in 25% of the study group. There was a significant
      variation in allergic reaction by sex (males 42%, females 12%) (P<0.01), use of
      catheters (yes 38%, no 13%) (P<0.05), and urologic surgery (yes 60%, no 18%)
      (P<0.01). The number of surgical procedures, age of patient, and V-P shunt were
      not significantly related to allergic reactions. CONCLUSIONS: Our findings
      support previous studies indicating a high prevalence of latex allergy among SB
      patients. The CAP test was a more sensitive measure of latex allergy in SB
      patients than SPT or latex challenge. There was significant correlation with
      urologic procedures and the use of urethral catheters.

PMID- 28767151
TI  - Pattern of food-induced anaphylaxis in children of an Asian community.

PMID- 28767152
TI  - Phenytoin hypersensitivity syndrome with fatal evolution.

PMID- 28767153
TI  - Soluble E-selectin correlates with disease activity in cyclosporin A-treated
      patients with atopic dermatitis.
AB  - BACKGROUND: The expression of adhesion molecules on endothelial cells regulates
      leukocyte migration. The level of soluble adhesion molecules which are shed into
      the circulation is known to reflect the degree of inflammation, and this level
      can therefore be used as an indicator of disease activity. The objective of this
      study was first to investigate the relationship between sE-selectin levels and
      disease activity parameters (scores of extent, severity, itch, and sleep) in
      atopic dermatitis (AD) patients, and second to determine the effect of therapy
      with an immunosuppressive drug (cyclosporin A) on sE-selectin levels. METHODS:
      Fourteen patients with severe AD and 41 healthy controls were studied. sE
      selectin was measured by ELISA both 2 weeks before therapy with cyclosporin A and
      after 16 weeks of treatment. RESULTS: At baseline, the level of sE-selectin was
      significantly higher in patients with AD than in healthy control subjects
      (P<0.0001). After treatment of AD with cyclosporin A, there was a significant
      reduction of the sE-selectin levels (P<0.0001). In addition, changes in sE
      selectin levels significantly correlated with changes in disease activity
      parameters such as severity (P<0.002) and extent of disease (P<0.049).
      CONCLUSIONS: Soluble E-selectin is a new serologic marker in AD which reflects
      disease activity. Therefore, soluble E-selectin may be a useful parameter in the
      monitoring of this disease. ABBREVIATIONS: AD: atopic dermatitis; sE-selectin:
      soluble E-selectin; CsA: cyclosporin A; SEM: standard error of mean; ELISA:
      enzyme-linked immunosorbent assay; VCAM: vascular adhesion molecule; ICAM:
      intercellular adhesion molecule; ELAM: endothelial cell-leukocyte adhesion
      molecule; LEC-CAM: leukocyte-endothelial cell - cellular adhesion molecule.

PMID- 28767154
TI  - Allergic contact dermatitis to propylene glycol.

PMID- 28767155
TI  - Seizures induced by NSAID.

PMID- 28767156
TI  - Prevalence of latex-specific IgE in blood donors: an Italian survey.

PMID- 28767157
TI  - Controversial aspects of adverse reactions to food.

PMID- 28767158
TI  - Latex and amoxicillin-provoked occupational asthma.

PMID- 28767159
TI  - Effects of in ovo exposure to 3,3',4,4'-tetrachlorobiphenyl (PCB 77) on heart
      development in tree swallow (Tachycineta bicolor).
AB  - Tree swallow (Tachycineta bicolor) eggs from 2 uncontaminated sites, the Patuxent
      Research Refuge (Laurel, MD, USA) and the Cobleskill Reservoir (Cobleskill, NY,
      USA) were dosed with polychlorinated biphenyl (PCB) 77 to evaluate effects on the
      developing cardiovascular system. To ensure embryonic viability, treatments were
      administered into the air cell at embryonic day 2.5 including: untreated
      (control), vehicle (filtered sterilized fatty acid mixture), 100 ng/g and 1000
      ng/g egg. Eggs were dosed in the field with 0.2 MUL/egg, returned to the nest,
      collected at embryonic day 13, hatched in the laboratory, and necropsied. The PCB
      77-treated hatchlings were compared with uninjected, vehicle-injected, and
      environmentally exposed hatchlings collected from a PCB-contaminated Upper Hudson
      River (NY, USA) site. The PCB 77-treated embryos showed no effects on hatching
      success or hatchling mortality, heart index, or morphological measures of 4
      distinct heart layers (heart width, length, septal thickness, total and
      ventricular cavity area) compared with controls. Hatchlings that had received PCB
      77 exhibited increased incidence of a cardiomyopathy and absence of the
      ventricular heart wall compact layer (Chi square test; p < 0.001);
      environmentally exposed embryos showed no apparent effects. The compact layer is
      essential in development and overall heart function for ventricular cardiomyocyte
      proliferation and normal heart contraction. The finding that in ovo exposure to
      PCB 77 resulted in distinct cardiomyopathy has implications for long-term
      individual fitness. Environ Toxicol Chem 2018;37:116-125. (c) 2017 SETAC.

PMID- 28767161
TI  - Comments on "supermicrosurgical lymphaticovenous anastomosis for a patient with
      breast lymphedema secondary to breast cancer treatment".

PMID- 28767160
TI  - Sunscreen creams containing naringenin nanoparticles: Formulation development and
      in vitro and in vivo evaluations.
AB  - BACKGROUND: The aim of this study was to develop sunscreen creams containing
      polymeric nanoparticles (NPs) of naringenin for photoprotective and antioxidant
      effects. METHODS: Polymeric NPs of naringenin were prepared and optimized. The
      NPs were incorporated into sunscreen creams and evaluated for in vitro and in
      vivo skin retention. RESULTS: The optimized naringenin NPs showed a size of 131.2
      nm, zeta potential -25.4 mV, and entrapment efficiency 32.45%. The absence of
      drug-excipient interaction was confirmed by Fourier transform infrared
      spectroscopy and differential scanning calorimetry. X-Ray diffraction analysis
      demonstrated the amorphization of naringenin in nanoparticles. Transmission
      electron microscopy showed the sphericity of the NPs with the size of <200 nm.
      Cytotoxicity assessment in HaCaT cells indicated non-toxic nature of naringenin
      NPs. In vitro skin permeation studies demonstrated that higher amount of
      naringenin permeated at the end of 12 hours (Q12 hours  = 184.03 +/- 3.37 MUg/cm2
      ) and deposited in the skin (10.38 +/- 0.48 MUg/cm2 ) from NPs as compared to
      plain naringenin. Sunscreen creams (SC1-SC5) containing plain naringenin or NPs
      with/without nano-zinc oxide and nano-titanium dioxide were prepared and
      evaluated. Optimized cream (SC5) containing naringenin NPs showed highest SPF
      value and enhanced skin retention of naringenin in comparison with NPs in
      suspension form and other cream formulations. CONCLUSION: Optimized
      nanoparticulate sunscreen cream exhibited highest skin retention and negligible
      skin permeation of naringenin besides showing excellent SPF value.

PMID- 28767162
TI  - Protective molecular mechanisms of resveratrol in UVR-induced Skin
      carcinogenesis.
AB  - Skin cancer is a major health problem worldwide. It is the most common cancer in
      the United States and poses a significant healthcare burden. Excessive UVR
      exposure is the most common cause of skin cancer. Despite various precautionary
      measures to avoid direct UVR exposure, the incidence of skin cancer and mortality
      related to it remains high. Furthermore, the current treatment options are
      expensive and have side effects including toxicity to normal cells. Thus, a safe
      and effective approach is needed to prevent and treat skin cancer.
      Chemopreventive strategy using naturally occurring compounds, such as
      resveratrol, is a promising approach to reduce the incidence of UVR-induced skin
      cancer and delay its progression. This review highlights the current body of
      evidence related to chemopreventive role of resveratrol and its molecular
      mechanisms in UVR-induced skin carcinogenesis.

PMID- 28767163
TI  - Predictors of sexual function in women with stress urinary incontinence.
AB  - AIMS: To assess female sexual function (SF) in different grades of urodynamic
      stress urinary incontinence (SUI), with/without pelvic organ prolapse (POP); to
      investigate associations between clinical data and pelvic organ prolapse/urinary
      incontinence sexual questionnaire (PISQ) scores. METHODS: A cross-sectional study
      was conducted in sexually active women (130 with SUI and 126 controls). Stamey
      score and POP quantification (POP-Q) were used. Urogynecological examinations
      were performed; all participants completed PISQ. Multivariable linear regression
      was used to identify negative SF predictors. RESULTS: SF was lower in the study
      group (P < 0.001), in moderate (P < 0.001), and severe SUI (P  < 0.02) versus
      controls, in each particular domain and total PISQ-score (total score: 83.8 +/-
      14.8, 80.8 +/- 14.5, 84.5 +/- 11.1 vs 95.7 +/- 10.3, respectively). Women with
      mild SUI had better SF in physical and partner-related domains compared to
      moderate SUI (33.6 +/- 6.1 vs 30.7 +/- 6.4, P < 0.02; 18.8 +/- 2.9 vs 17.3 +/-
      3.3, P = 0.02, respectively). Age correlated with PISQ-scores in
      behavioral/emotive (r = -0.24, P = 0.006), and partner-related domains (r = 
      0.28, P = 0.002), and total PISQ-score (r = -0.2, P = 0.02); menopausal status
      with partner-related domain (r = -0.32, P = 0.000) and total PISQ-score (r = 
      0.19, P = 0.029); menopause duration with physical domain (r = 0.17, P = 0.045);
      SUI stage only with PISQ scores in physical domain (r = -0.22, P = 0.014). No
      correlations were found between BMI, parity, number of vaginal deliveries, POP-Q
      stages, with PISQ results. Age in the SUI group and controls (beta = -0.18, P <
      0.05) and BMI in controls (beta = -0.26, P < 0.01) were independent predictors of
      impaired SF. CONCLUSIONS: Different SF predictors were found in SUI women and
      controls. Impaired SF was confirmed in SUI women compared to controls, with more
      severe SUI corresponding to lower SF.

PMID- 28767164
TI  - Probable acute Epstein-Barr virus encephalitis in a 6-year-old girl.

PMID- 28767165
TI  - Efficient and Selective N-Methylation of Nitroarenes under Mild Reaction
      Conditions.
AB  - Herein, we report a straightforward protocol for the preparation of N,N
      dimethylated amines from readily available nitro starting materials using formic
      acid as a renewable C1 source and silanes as reducing agents. This tandem process
      is efficiently accomplished in the presence of a cubane-type Mo3 PtS4 catalyst.
      For the preparation of the novel [Mo3 Pt(PPh3 )S4 Cl3 (dmen)3 ]+ (3+ ) (dmen:
      N,N'-dimethylethylenediamine) compound we have followed a [3+1] building block
      strategy starting from the trinuclear [Mo3 S4 Cl3 (dmen)3 ]+ (1+ ) and Pt(PPh3 )4
      (2) complexes. The heterobimetallic 3+ cation preserves the main structural
      features of its 1+ cluster precursor. Interestingly, this catalytic protocol
      operates at room temperature with high chemoselectivity when the 3+ catalyst co
      exists with its trinuclear 1+ precursor. N-heterocyclic arenes, double bonds,
      ketones, cyanides and ester functional groups are well retained after N
      methylation of the corresponding functionalized nitroarenes. In addition,
      benzylic-type as well as aliphatic nitro compounds can also be methylated
      following this protocol.

PMID- 28767166
TI  - Radiological anatomy of the perforators of the gluteal region: The "radiosome"
      based anatomy.
AB  - BACKGROUND: The superior (SGA) and the inferior gluteal artery (IGA) perforator
      flaps are widely used in pressure-sore repair and in breast reconstruction. The
      aim was to exhaustively depict the topographical anatomy of the whole system of
      perforators in the buttock. METHODS: Eighty lower-extremity computed tomographic
      angiography (CTA) of patients (20 males/20 females, mean age 61-years old, range
      38-81) were considered. The source artery, location, type, and caliber of gluteal
      perforators were analyzed. The location of perforators was reproduced using a
      standardized two-dimensional grid on the coronal plane, centered onto defined
      bone landmarks. We defined "radiosome" the cutaneous vascular territory of a
      source artery inferred through the representation of its whole perforator system
      at the exit point through the deep fascia. RESULTS: A mean number of 25.6 +/- 5.7
      perforators in the gluteal region was observed, distributed as follows: 11.6 +/-
      4.8(45.2%) from SGA; 7.9 +/- 4.5(30.8%) from IGA; 1.5 +/- 0.8(5.8%) from fifth
      lumbar artery; 1.2 +/- 0.8(4.7%) from internal pudendal artery; 1.2 +/- 1(4.8%)
      from lateral circumflex femoral artery; 0.3 +/- 0.7(1.2%) from circumflex iliac
      superficial artery. At least one large (internal diameter > 1 mm) SGA
      septocutaneous perforator was present in 77.5% of patients. CONCLUSIONS: The
      gluteal region is vascularized by perforators of multiple source arteries.
      Septocutaneous perforators of SGA and IGA were planned along a curve drawn from
      the posterior-superior border of the iliac crest to the greater trochanter. The
      lumbar artery perforators are clustered over the apex of the iliac crest; the
      internal pudendal artery perforators are clustered medially to the ischiatic
      tuberosity. Contributions can also come from the sacral and superficial
      circumflex iliac arteries.

PMID- 28767167
TI  - The impact of age and sex on the reporting of cough and angioedema with renin
      angiotensin system inhibitors: a case/noncase study in VigiBase.
AB  - The purpose of this study was to assess the impact of age and sex on the
      reporting of cough and angioedema related to renin-angiotensin system (RAS)
      inhibitors. A case/noncase study was performed in VigiBase. Two case groups were
      identified, reports of cough and reports of angioedema, and noncases were all
      reports of all other adverse events. Logistic regression analysis was used to
      assess the association between reporting of cough and angioedema with each class
      of RAS inhibitors stratified by age/sex and to control for confounding. The
      reporting of cough with angiotensin-converting enzyme (ACE) inhibitors was
      significantly higher in women than in men [adjusted reporting odds ratio (ROR):
      44.0, 95% CI (43.2-44.8) for women vs. 29.2, 95% CI (28.5-29.9) for men]. There
      was no difference in reporting of cough linked to angiotensin receptor blockers
      (ARBs) and aliskiren between men and women. In contrast, the reporting of
      angioedema with ACE inhibitors and ARBs was significantly higher in men than in
      women, but for aliskiren, women had a significantly higher ROR than men [adjusted
      ROR: 5.20, 95% CI (4.18-6.46) for women vs. 3.04, 95% CI (2.30-4.02) for men].
      The reporting of cough with ACE inhibitors was increased with age until reaching
      a plateau at middle adulthood (40-59 years) and the reporting of angioedema with
      ACE inhibitors was increased with age until elderly (60-79 years). Age had only a
      slight effect on the reporting of cough and angioedema with ARBs and aliskiren.
      Both age and sex have substantial effects on the reporting of cough and
      angioedema with RAS inhibitors and in particular ACE inhibitors. Further study is
      needed to determine whether these differences mainly express different adverse
      drug reaction risks in subgroups or also can be explained by factors influencing
      reporting.

PMID- 28767168
TI  - The possibility of free tissue transfer as a nutrient flap for critical ischemic
      foot: A case report.
AB  - Microsurgical procedure of free tissue transfer in critical limb ischemia
      patients with large ulceration has already been established. The nutrient flap
      concept was that transferred tissue functioned not only to cover the skin defect
      but also as a supplementary blood supply to the ischemic lower leg. This report
      showed the justification for this concept, which was rarely discussed. A 58-year
      old male patient with progressive forefoot gangrene caused by arteriosclerosis
      obliterans was presented. The distal bypass procedure was performed as
      revascularization surgery, and a latissimus dorsi (LD) myocutaneous flap was
      transplanted to cover ulceration. The arterial pedicle of the flap was
      anastomosed to the vein graft in an end-to-end manner, and the venous pedicle was
      anastomosed to the posterior tibialis vein in an end-to-end manner. Bypass graft
      blood flow went straight to the LD flap only. The postoperative course was
      uneventful. The free flap and right foot survived successfully and the patient
      was ambulatory with no recurrence of ulceration wearing order-made shoes more
      than three years after transplantation. Vessel-selective angiography was
      performed two months after surgery. An angiographic catheter was inserted into
      the bypass graft, which ran straight through the flap nutrient artery. The
      results obtained showed that not only the transferred flap area, but also the
      remaining original foot soft tissue (including the sole and heel) was clearly
      visualized radiologically only through the flap nutrient vessel. This findings of
      the angiography appear to provide direct evidence for the nutrient flap concept.

PMID- 28767169
TI  - Urodynamic and molecular characteristics of detrusor underactivity in a rat
      cryoinjury model and effects of low energy shock wave therapy.
AB  - AIMS: Low energy shock wave (LESW) has been shown to facilitate tissue
      regeneration and reduce inflammation. We investigated the effects of LESW in an
      underactive (DU) model induced by cryoinjury of rat detrusor. METHODS: Forty-six
      female Sprague-Dawley rats were divided into sham, cryoinjury with or without
      LESW (0.12 mJ/mm2 ; 200 pulses). Under halothane anesthesia, a low midline
      incision was made and a cryoinjury of detrusor was induced by placing an aluminum
      rod (chilled with dry ice) for 30 s on the serosal side of the bladder filled
      with 1 mL sterile saline bilaterally. Awake cystometrogram (CMG), molecular and
      histopathology studies were performed on Day 8 or 15 after cryoinjury. RESULTS:
      Significant urodynamic, histological, and molecular changes induced by cryoinjury
      of rat detrusor were detected on Day 8 and decrease in the contraction amplitude
      (54.3%), a significant increase in wet bladder weight (64.1%), edematous changes,
      muscle thinning and downregulation of alpha-SMA, IL-6, and upregulation of COX-2.
      LESW reversed the cryoinjury induced histological and COX-2 expression to cause a
      49.0% increase in the contraction amplitude (P < 0.05). LESW induced cell
      proliferation was revealed by increased CD31 and Ki67 immunostaining. The effect
      of cryoinjury on urodynamic and histological changes was maintained till Day 15.
      CONCLUSION: The cryoinjury of rat detrusor models myogenic DU, which is partially
      reversed by LESW. LESW may afford a simple, non-invasive modality to facilitate
      tissue regeneration and improve voiding function in myogenic detrusor
      underactivity.

PMID- 28767170
TI  - What about physical contacts between epidermal keratinocytes and sensory neurons?
AB  - Recent studies have demonstrated that keratinocytes closely participate in
      sensory transduction, and therefore, intra-epidermal free nerve endings are not
      exclusive transducers of pain. This discovery implies the existence of close
      afferent communication from keratinocytes to sensory neurons. Although reciprocal
      interactions between keratinocytes and intra-epidermal free nerve endings via
      soluble mediators are well established, little attention has been paid to
      physical contacts between keratinocytes and intra-epidermal free nerve endings.
      This review proposes to consider the ultrastructural and functional knowledge of
      these contacts, in both human skin biopsies and keratinocyte-sensory neuron
      cocultures to speculate on the possible existence of synaptic contacts.

PMID- 28767171
TI  - Partitioning of PCBs from air to clothing materials in a Danish apartment.
AB  - Polychlorinated biphenyl (PCB) contamination of buildings continues to pose an
      exposure threat, even decades after their application in the form of calks and
      other building materials. In this research, we investigate the ability of
      clothing to sorb PCBs from contaminated air and thereby influence exposure. The
      equilibrium concentration of PCB-28 and PCB-52 was quantified for nine used
      clothing fabrics exposed for 56 days to air in a Danish apartment contaminated
      with PCBs. Fabric materials included pure materials such as cotton and polyester,
      or blends of polyester, cotton, viscose/rayon, and/or elastane. Air
      concentrations were fairly stable over the experimental period, with PCB-28
      ranging from 350 to 430 ng/m3 and PCB-52 ranging from 460 to 550 ng/m3 . Mass
      accumulated in fabric ranged from below detection limits to 4.5 mg/g of fabric.
      Cotton or materials containing elastane sorbed more than polyester materials on a
      mass basis. Mass-normalized partition coefficients above detection limits ranged
      from 105.7 to 107.0  L/kg. Clothing acts as a reservoir for PCBs that extends
      dermal exposure, even when outside or in uncontaminated buildings.

PMID- 28767172
TI  - Are nomograms based on free uroflows helpful to evaluate urethral obstruction in
      men?
AB  - AIMS: It was demonstrated earlier that reduced maximum flow-rate (Qmax ) during
      intubated flow (IF) in women may be the consequence of a urethral reflex. Over
      estimation of outflow obstruction is the consequence. Our hypothesis, that a
      similar phenomenon could occur in men, is tested using results of a free uroflow
      (FF) preceding an IF to eventually correct the Abrams-Griffiths (AG) number.
      METHODS: Retrospectively, analysis of 441 urodynamic studies of men suspected of
      bladder outflow obstruction (BOO) was performed. The Valentini-Besson-Nelson
      model links outflow obstruction (parameter pucp) and the detrusor contractility
      (parameter k) to Qmax and detrusor pressure at Qmax (pdet.Qmax ). AG and pucp are
      strongly correlated. Contractility is described by a graphical representation (a
      nomogram) which numerical fitting is an algebraic equation f(Qmax ,pdet.Qmax ).
      Nomograms based on IF allowed computing a calculated AG (corr-AG) on the basis of
      free flow. RESULTS: Included files (N = 362) had filling volume during FF > 90
      mL; corr-AG was compared to AG. When Qmax.FF  > 1.5*Qmax.IF (N = 114), 61
      patients (53.5%) were found less obstructed with corr-AG, no one more obstructed.
      Increased BOO could be the result of a urethral reflex during IF and AG gave an
      overestimation. When Qmax.FF  < 1.5*Qmax.IF (N = 248), only 39 patients (12.1%)
      were found less obstructed with corr-AG and 28 (11.3%) more obstructed.
      CONCLUSION: To obtain a reliable evaluation of BOO in men, it is suitable to
      perform a FF before IF. A corrected AG (corr-AG) obtained from IF analysis and
      nomograms based on FF may be helpful for evaluation of BOO in men.

PMID- 28767173
TI  - Prevalence, presentation and treatment of lower limb pathologies in juvenile
      idiopathic arthritis: A narrative review.
AB  - Juvenile idiopathic arthritis is a chronic, autoimmune, inflammatory joint
      disease. It is the most common arthritis in children and adolescents. This paper
      reviews the presentation and treatment of lower limb pathologies in juvenile
      idiopathic arthritis from an allied health perspective. Common lower limb
      pathologies include: synovitis causing swelling, tenderness and pain; persistent
      inflammation leading to flexion contractures; limb length discrepancies; muscle
      atrophy; enthesopathies such as plantar fasciitis and Achilles tendonitis; and
      tenosynovitis. Allied health professionals may use a range of non-invasive
      therapies, including hydrotherapy, strengthening and stretching exercises,
      massaging, taping and foot orthoses to manage lower limb pathologies in juvenile
      idiopathic arthritis. Early detection and treatment of these common and
      potentially disabling lower limb pathologies are fundamental to achieving gold
      standard care for children with juvenile idiopathic arthritis.

PMID- 28767174
TI  - Inactivation of Beclin-1-dependent autophagy promotes ursolic acid-induced
      apoptosis in hypertrophic scar fibroblasts.
AB  - A hypertrophic scar (HS) is caused by abnormal proliferation of dermal
      fibroblasts. Thus, promoting hypertrophic scar fibroblast (HSFB) apoptosis is an
      effective strategy for HS therapy. Ursolic acid (UA) has been widely used as an
      inducer of apoptosis in diverse cancers. However, whether UA plays an inhibitory
      role in HS formation is still unknown. In our study, UA was used to treat HSFBs
      and the cell viability, apoptosis, and collagen synthesis were determined by a
      Cell Counting Kit 8 assay, flow cytometry, and an H3 -proline incorporation
      assay, respectively. Autophagy activity was detected by LC3 immunoblotting and
      electron microscopy, and siRNAs targeting Beclin-1 were used to inhibit
      autophagy. Western blotting was performed to investigate the molecular changes in
      HSFBs after various treatments. We found that UA inhibited collagen synthesis and
      induced cell apoptosis in HSFBs, evidenced by the deregulated expression of Bim,
      Bcl-2 and Cyto C. Furthermore, we demonstrated that UA induced autophagy and
      inactivation of autophagy promoted UA-induced apoptosis and collagen synthesis
      inhibition in HSFBs. Molecular investigation indicated that UA-induced autophagy
      through upregulation of Beclin-1 and knockdown of Beclin-1 prevent UA-induced
      autophagy. Overexpression of Bcl-2 prevents UA-induced autophagy, Beclin-1
      upregulation, apoptosis and collagen synthesis inhibition in HSFBs. Collectively,
      our study demonstrated that UA is a novel agent for inhibiting HS formation by
      promoting apoptosis, especially in combination with an autophagy inhibitor. Our
      results provide strong evidence of the application of UA in clinical HS
      treatment.

PMID- 28767175
TI  - Acknowledging medical students' reports of intimidation and humiliation by their
      teachers in hospitals.
AB  - AIM: The continuing existence of 'teaching by humiliation' of medical students
      and junior doctors in Australia has recently been highlighted in a number of
      research publications and media reports. This study investigates medical
      students' experiences of being intimidated or humiliated during their clinical
      rotations in Australian hospitals in paediatrics and adult medicine. METHODS:
      From factors identified in earlier research, a two-page survey was developed for
      administration at two Australian medical schools. Administered in Semester 2 of
      2014, students were invited to add their own free-text comments at the conclusion
      of 17 closed questions. Using thematic analysis of the qualitative data, the
      researchers identified the common themes in the students' free-text comments,
      which are reported in this paper. RESULTS: We found five main themes in the
      qualitative data: a spectrum of interpretations of and responses to 'teaching by
      humiliation', an accepted means of enculturating the young, teachers' techniques
      for asking questions, the victims and perpetrators of mistreatment and the
      variance of prevalence in different contexts. CONCLUSION: Research shows the
      persistence of 'teaching by humiliation', even in paediatrics, particularly when
      doctors are questioning students in ways that shame them for their lack of
      knowledge. Given the many personal and professional costs of these practices,
      this cycle of mistreatment needs to be brought to an end. There is a need for
      students' reports of intimidation and humiliation to be acknowledged; the
      offending practices need to be interrupted, and more effective and respectful
      approaches to teaching need to be adopted.

PMID- 28767176
TI  - Sequential chimeric medial femoral condyle and anterolateral thigh flow-through
      flaps for one-stage reconstructions of composite bone and soft tissue defects:
      Report of three cases.
AB  - Small recalcitrant non-unions with poor perfusion require reconstruction with
      vascularized bone flaps. Cases with concomitant large soft tissue defects are
      especially challenging, since vascularized soft tissue transfer is often
      indicated and distant microvascular anastomoses may be required. We introduce a
      sequential chimeric free flap composed of a medial femoral condyle
      corticoperiosteal flap anastomosed to an anterolateral thigh flow-through flap
      (MFC-ALT flap) and report its use for reconstruction of small non-unions with
      concomitant large soft tissue defects in three exemplary patients. Two female and
      one male patients ages 39-58 years suffered from composite bone and soft tissue
      defects of the lower extremity and clavicle caused by tumor resection and
      postoperative radiation resp. infected tibial pilon fracture. The sizes of the
      soft tissue defects ranged from 15-23 * 4.5-6 cm and the sizes of the bone
      defects ranged from 1.5-4 * 2-4 cm. Defect reconstructions were performed in all
      cases with sequential chimeric MFC-ALT flaps with sizes ranging from 2-4 * 1.6-4
      cm for the MFC and 21-23 * 7-8 cm for the ALT skin paddles. Functional
      reconstructions were achieved in all cases resulting in stable unions and soft
      tissue coverage enabling the patients to bear full weight without assistance on 5
      months follow-up. Postoperative course was uneventful and complications were
      restricted to a small skin necrosis at the suture line in one case. MFC-ALT flaps
      may be a safe, and effective procedure for one-stage reconstructions of small,
      irregularly shaped bone defects with concomitant large soft tissue loss or
      surrounding instable scarring, particularly in cases of recalcitrant non-unions
      after radiation exposure.

PMID- 28767177
TI  - Phosphorylation-dependent signaling controls degradation of DNA mismatch repair
      protein PMS2.
AB  - MutLalpha, a heterodimer consisting of MLH1 and PMS2, plays an important role in
      DNA mismatch repair and has been shown to be additionally involved in several
      other important cellular mechanisms. Previous work indicated that AKT could
      modulate PMS2 stability by phosphorylation. Still, the mechanisms of regulation
      of MutLalpha remain unclear. The stability of MutLalpha subunits was investigated
      by transiently overexpression of wild type and mutant forms of MLH1 and PMS2
      using immunoblotting for measuring the protein levels after treatment. We found
      that treatment with the cell-permeable serine/threonine phosphatase inhibitor,
      Calyculin, leads to degradation of PMS2 when MLH1 or its C-terminal domain is
      missing or if amino acids of MLH1 essential for PMS2 interaction are mutated. In
      addition, we discovered that the C-terminal tail of PMS2 is relevant for this
      Calyculin-dependent degradation. A direct involvement of AKT, which was
      previously described to be responsible for PMS2 degradation, could not be
      detected. The multi-kinase inhibitor Sorafenib, in contrast, was able to avoid
      the degradation of PMS2 which postulates that cellular phosphorylation is
      involved in this process. Together, we show that pharmacologically induced
      phosphorylation by Calyculin can induce the selective proteasome-dependent
      degradation of PMS2 but not of MLH1 and that the PMS2 degradation could be
      blocked by Sorafenib treatment. Curiously, the C-terminal Lynch Syndrome-variants
      MLH1L749P and MLH1Y750X make PMS2 prone to Calyculin induced degradation.
      Therefore, we conclude that the specific degradation of PMS2 may represent a new
      mechanism to regulate MutLalpha.

PMID- 28767178
TI  - Chemokine receptor-7 (CCR7) deficiency leads to delayed development of joint
      damage and functional deficits in a murine model of osteoarthritis.
AB  - Elevated chemokine receptor Ccr7 is observed in knee osteoarthritis (OA) and
      associated with severity of symptoms. In this study, we confirmed that CCR7
      protein expression is elevated in synovial tissue from OA patients by
      immunohistochemical staining. We then investigated whether Ccr7 deficiency
      impacted structural and functional joint degeneration utilizing a murine model of
      OA. OA-like disease was induced in male C57BL/6 and Ccr7-deficient (Ccr7-/- )
      mice by destabilization of the medial meniscus (DMM). Functional deficits were
      measured by computer integrated monitoring of spontaneous activity every 4 weeks
      after DMM surgery up 16 weeks. Joint degeneration was evaluated at 6 and 19 weeks
      post-surgery by histopathology, and subchondral bone changes analyzed by microCT.
      Results showed reduction in locomotor activities in DMM-operated C57BL/6 mice by
      8 weeks, while activity decreases in Ccr7-/- mice were delayed until 16 weeks.
      Histopathologic evaluation showed minimal protection from early cartilage
      degeneration (p = 0.06) and osteophytosis (p = 0.04) in Ccr7-/- mice 6 weeks post
      DMM compared to C57BL/6 controls, but not at 19 weeks. However, subchondral bone
      mineral density (p = 0.03) and histologic sclerosis (p = 0.02) increased in
      response to surgery in C57BL/6 mice at 6 weeks, while Ccr7-/- mice were protected
      from these changes. Our results are the first to demonstrate a role for Ccr7 in
      early development of functional deficits and subchondral bone changes in the DMM
      model. Understanding the mechanism of Ccr7 receptor signaling in the initiation
      of joint pathology and disability will inform the development of innovative
      therapies to slow symptomatic OA development after injury. Published 2017. This
      article is a U.S. Government work and is in the public domain in the USA. J
      Orthop Res 36:864-875, 2018.

PMID- 28767179
TI  - Upregulation of microRNA-135b and microRNA-182 promotes chemoresistance of
      colorectal cancer by targeting ST6GALNAC2 via PI3K/AKT pathway.
AB  - MicroRNAs (miRNAs) are increasingly involved in the development of drug
      resistance, including 5-fluorouracil (5-FU) resistance in colorectal cancer
      (CRC). Aberrant sialylation is correlated with human CRC. The study was to
      explore whether miR-135b and miR-182 modulated 5-FU chemoresistance of CRC by
      targeting ST6GALNAC2 via PI3K/AKT pathway. MiR-135b and miR-182 were found to be
      up-regulated in CRC tissues and 5-FU resistant CRC cell lines. Forced miR-135b
      and miR-182 expression also affected ST6GALNAC2 levels. Using reporter-gene
      assay, ST6GALNAC2 was identified as direct target of miR-135b and miR-182, while
      ST6GALNAC2 expression exhibited patterns opposite to that of miR-135b and miR-182
      in CRC samples and cell lines. Interestingly, up-regulation of miR-135b or miR
      182 increased drug resistance and proliferation, but decreased apoptosis in 5-FU
      resistant CRC cell lines. Suppression of these miRNAs implicated an inverse
      function, while altered expression of ST6GALNAC2 mediated CRC progression upon
      transfection with miR-135b/-182 mimic or inhibitor. Furthermore, miR-135b and miR
      182 were clarified to regulate the activity of phosphoinositide-3 kinase
      (PI3K)/AKT pathway. Inhibition of the PI3K/AKT pathway enhanced the
      chemosensitivity to 5-FU in HCT-8/5-FU and LoVo/5-FU. Taken together, miR-135b
      and miR-182 may reverse the resistance to 5-FU in CRC cells by targeting
      ST6GALNAC2 via PI3K/AKT pathway, which render potential chemotherapy targets for
      the treatment of CRC.

PMID- 28767180
TI  - Improved union and bone strength in a mouse model of NF1 pseudarthrosis treated
      with recombinant human bone morphogenetic protein-2 and zoledronic acid.
AB  - Tibial pseudarthrosis associated with Neurofibromatosis type 1 (NF1) is an
      orthopedic condition with consistently poor clinical outcomes. Using a murine
      model that features localized double inactivation of the Nf1 gene in an
      experimental tibial fracture, we tested the effects of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) and/or the bisphosphonate zoledronic acid (ZA).
      Tibiae were harvested at 3 weeks for analysis, at which time there was negligible
      healing in un-treated control fractures (7% union). In contrast, rhBMP-2 and
      rhBMP-2/ZA groups showed significantly greater union (87% and 93%, p < 0.01 for
      both). Treatment with rhBMP-2 led to a 12-fold increase in callus bone volume and
      this was further increased in the rhBMP-2/ZA group. Mechanical testing of the
      healed rhBMP-2 and rhBMP-2/ZA fractures showed that the latter group had
      significantly higher mechanical strength and was restored to that of the un
      fractured contralateral leg. Co-treatment with rhBMP-2/ZA also reduced fibrous
      tissue infiltration at the fracture site compared to rhBMP alone (p = 0.068).
      These data support the future clinical investigation of this combination of
      anabolic and anti-resorptive agents for the treatment of NF1 pseudarthrosis. (c)
      2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
      Res 36:930-936, 2018.

PMID- 28767181
TI  - Split pedicle for bilateral free deep inferior epigastric perforator flap breast
      reconstruction: Use of contralateral recipient vessels with radiotherapy damage.

PMID- 28767182
TI  - Airborne bacterial assemblage in a zero carbon building: A case study.
AB  - Currently, there is little information pertaining to the airborne bacterial
      communities of green buildings. In this case study, the air bacterial community
      of a zero carbon building (ZCB) in Hong Kong was characterized by targeting the
      bacterial 16S rRNA gene. Bacteria associated with the outdoor environment
      dominated the indoor airborne bacterial assemblage, with a modest contribution
      from bacteria associated with human skin. Differences in overall community
      diversity, membership, and composition associated with short (day-to-day) and
      long-term temporal properties were detected, which may have been driven by
      specific environmental genera and taxa. Furthermore, time-decay relationships in
      community membership (based on unweighted UniFrac distances) and composition
      (based on weighted UniFrac distances) differed depending on the season and
      sampling location. A Bayesian source-tracking approach further supported the
      importance of adjacent outdoor air bacterial assemblage in sourcing the ZCB
      indoor bioaerosol. Despite the unique building attributes, the ZCB microbial
      assemblage detected and its temporal characteristics were not dissimilar to that
      of conventional built environments investigated previously. Future controlled
      experiments and microbial assemblage investigations of other ZCBs will
      undoubtedly uncover additional knowledge related to how airborne bacteria in
      green buildings may be influenced by their distinctive architectural attributes.

PMID- 28767183
TI  - Identification of glutathione S-transferases in Bemisia tabaci (Hemiptera:
      Aleyrodidae) and evidence that GSTd7 helps explain the difference in insecticide
      susceptibility between B. tabaci Middle East-Minor Asia 1 and Mediterranean.
AB  - The Bemisia tabaci (Gennadius) (Hemiptera:Aleyrodidae) species complex includes
      invasive and destructive pests of field crops, and the sibling species MEAM1 and
      MED are its two most damaging members. Previous research indicated that the
      replacement of Middle East-Minor Asia 1 (MEAM1) by Mediterranean (MED) as the
      dominant B. tabaci species in China can be mainly attributed to MED's greater
      tolerance to insecticides. Glutathione S-transferases (GSTs) play important roles
      in the detoxification of hydrophobic toxic compounds. To increase our
      understanding of differences in insecticide resistance between B. tabaci MEAM1
      and MED, we searched the genomic and transcriptomic databases and identified 23
      putative GSTs in both B. tabaci MEAM1 and MED. Through measuring mRNA levels of
      18 of the GSTs after B. tabaci MEAM1 and MED adults were exposed to the
      insecticide imidacloprid, we found that the expression levels were increased more
      in B. tabaci MED than in MEAM1 (in particular, the expression level of GST-d7 was
      increased by 4.39-fold relative to the control). Knockdown of GST-d7 in B. tabaci
      MED but not in B. tabaci MEAM1 resulted in a substantial increase in the
      mortality of imidacloprid-treated adults. These results indicate that differences
      in GST-d7 may help explain why insecticide tolerance is greater in B. tabaci MED
      than in B. tabaci MEAM1.

PMID- 28767184
TI  - Antithrombin III prevents progression of chronic kidney disease following
      experimental ischaemic-reperfusion injury.
AB  - Acute kidney disease (AKI) leads to increased risk of progression to chronic
      kidney disease (CKD). Antithrombin III (ATIII) is a potent anticoagulant with
      anti-inflammatory properties, and we previously reported that insufficiencies of
      ATIII exacerbated renal ischaemia-reperfusion injury (IRI) in rats. In this
      study, we examined the characteristic of AKI-CKD transition in rats with two
      distinct AKI models. Based on our observation, left IRI plus right nephrectomy
      (NX-IRI) was used to determine whether ATIII had therapeutic effects in
      preventing CKD progression after AKI. It was observed that NX-IRI resulted in
      significant functional and histological damage at 5 weeks after NX-IRI compared
      with sham rats, which was mitigated by ATIII administration. Besides, we noticed
      that ATIII administration significantly reduced NX-IRI-induced interstitial
      fibrosis. Consistently, renal expression of collagen-1, alpha-smooth muscle actin
      and fibronectin were substantial diminished in ATIII-administered rats compared
      with un-treated NX-IRI rats. Furthermore, the beneficial effects of ATIII were
      accompanied with decreased M1-like macrophage recruitment and down-regulation of
      M1-like macrophage-dependent pro-inflammatory cytokines such as tumour necrosis
      factor alpha, inducible nitric oxide synthase and interleukin-1beta, indicating
      that ATIII prevented AKI-CKD transition via inhibiting inflammation. Overall,
      ATIII shows potential as a therapeutic strategy for the prevention of CKD
      progression after AKI.

PMID- 28767185
TI  - Lessons Learned from Alzheimer Disease: Clinical Trials with Negative Outcomes.

PMID- 28767186
TI  - Diagnosis of Subarachnoid Hemorrhage: Time for a Paradigm Shift?

PMID- 28767187
TI  - Phenotype analysis of congenital and neurodevelopmental disorders in the next
      generation sequencing era.
AB  - The designation, phenotype, was proposed as a term by Wilhelm Johannsen in 1909.
      The word is derived from the Greek, phano (showing) and typo (type), phanotypos.
      Phenotype has become a widely recognized term, even outside of the genetics
      community, in recent years with the ongoing identification of human disease
      genes. The term has been defined as the observable constitution of an organism,
      but sometimes refers to a condition when a person has a particular clinical
      presentation. Analysis of phenotype is a timely theme because advances in the
      understanding of the genetic basis of human disease and the emergence of next
      generation sequencing have spurred a renewed interest in phenotype and the
      proposal to establish a "Human Phenome Project." This article summarizes the
      principles of phenotype analysis that are important in medical genetics and
      describes approaches to comprehensive phenotype analysis in the investigation of
      patients with human disorders. I discuss the various elements related to disease
      phenotypes and highlight neurofibromatosis type 1 and the Elements of Morphology
      Project as illustrations of the principles. In recent years, the notion of "deep
      phenotyping" has emerged. Currently there are now a number of proposed strategies
      and resources to approach this concept. Not since the 1960s and 1970s has there
      been such an exciting time in the history of medicine surrounding the analysis of
      phenotype in genetic disorders.

PMID- 28767188
TI  - LINC01101 and LINC00277 expression levels as novel factors in HPV-induced
      cervical neoplasia.
AB  - Recently long non-coding RNAs were identified as new factors involved in gene
      expression regulation. To gain insight into expression pattern of these factors
      related to E7 HPV18 oncogene, this study uses HeLa cell culture transfected with
      E7-siRNA. Gene expression profile was investigated using microarray analysis.
      After analysing the microarray results, we identified 15,387 RNA species
      differentially expressed in E7-siRNA-transfected cells compared with controls
      (fold change >2). The expression profiles of lncRNA species highlighted 731
      lncRNAs and 203 lincRNAs. We selected two lincRNAs (LINC01101 and LINC00277) and
      we evaluated the expression profile in HPV-induced neoplasia. Both lincRNAs
      investigated display a significantly reduced pattern of expression in cervical
      lesions and cancer, associated with clinical parameters. A connection between HPV
      presence and lincRNAs was noted. hrHPV-positive samples exhibit significantly
      reduced LINC01101 and LINC00277 expression level (P < 0.05). These results
      provide new insights into involvement of lncRNA in HPV-induced cervical cancer,
      enriching our understanding of their potential role in this pathology.

PMID- 28767190
TI  - Insulin degludec in the first trimester of pregnancy: Report of two cases.
AB  - Insulin degludec is an extra-long-acting insulin analog that allows for enhanced
      efficacy and flexibility in the injection time. However, it is not approved for
      use during pregnancy. We report the pregnancy outcome and newborn conditions in
      two women with type 1 diabetes who continued preconception degludec treatment
      during embryogenesis. No pregnancy complication or congenital neonatal
      malformation was observed. Both babies presented with hypoglycemia and required
      neonatal intensive care unit admission. Degludec treatment did not cause adverse
      effects in the mothers or malformations in the newborns. The observed neonatal
      complications were probably independent of early pregnancy degludec treatment.

PMID- 28767191
TI  - Assessing the Stability of Fluorescently Encoded Nanoparticles in Lysosomes by
      Using Complementary Methods.
AB  - Nanoparticles (NPs) are promising tools in biomedical research. In vitro testing
      is still the first method for initial evaluation; however, NP colloidal behavior
      and integrity, in particular inside cells (that is, in lysosomes), are largely
      unknown and difficult to evaluate because of the complexity of the environment.
      Furthermore, while the majority of NPs are usually labeled with fluorescent dyes
      for tracking purposes, the effect of the lysosomal environment on the fluorophore
      properties, as well as the ensuing effects on data interpretation, is often only
      sparsely addressed. In this work, we have employed several complementary
      analytical methods to better understand the fate of fluorescently encoded NPs and
      identify potential pitfalls that may arise from focusing primary analysis on a
      single attribute, for example, fluorophore detection. Our study shows that in a
      lysosomal environment NPs can undergo significant changes resulting in dye
      quenching and distorted fluorescence signals.

PMID- 28767192
TI  - Expanding the phenotype of DST-related disorder: A case report suggesting a
      genotype/phenotype correlation.
AB  - The gene DST encodes for the large protein BPAG1 involved in hemidesmosomes. Its
      alternative splicing gives rise to tissue-enriched isoforms in brain, muscle, and
      skin. The few patients described so far with bi-allelic mutations in the DST gene
      have either a skin phenotype of epidermolysis bullosa simplex or a neurological
      phenotype. Here, we report a 17-year-old female individual presenting with a more
      complex phenotype consisting of both skin and neuronal involvement, in addition
      to several previously unreported findings, such as iris heterochromia, cataract,
      hearing impairment, syringomyelia, behavioral, and gastrointestinal issues,
      osteoporosis, and growth hormone deficiency. Family-trio whole exome sequencing
      revealed that she was a compound heterozygous for two variants in the DST gene
      with highly-predicted functional impact, c.3886A>G (p.R1296X) in exon 29 and
      c.806C>T (p.H269R) in exon 7. Interestingly, exon 7 is included in the neuronal
      isoform whereas exon 29 is expressed in both skin and neuronal isoforms. The
      patient we described is the first case with a mutation affecting an exon
      expressed in both the neuronal and skin isoforms that can explain the more
      complex phenotype compared to previously reported cases.

PMID- 28767189
TI  - Administration of signalling molecules dictates stem cell homing for in situ
      regeneration.
AB  - Ex vivo-expanded stem cells have long been a cornerstone of biotherapeutics and
      have attracted increasing attention for treating intractable diseases and
      improving tissue regeneration. However, using exogenous cellular materials to
      develop restorative treatments for large numbers of patients has become a major
      concern for both economic and safety reasons. Advances in cell biological
      research over the past two decades have expanded the potential for using
      endogenous stem cells during wound healing processes, and in particular, recent
      insight into stem cell movement and homing has prompted regenerative research and
      therapy based on recruiting endogenous cells. Inspired by the natural healing
      process, artificial administration of specific chemokines as signals systemically
      or at the injury site, typically using biomaterials as vehicles, is a state-of
      the-art strategy that potentiates stem cell homing and recreates an anti
      inflammatory and immunomodulatory microenvironment to enhance in situ tissue
      regeneration. However, pharmacologically coaxing endogenous stem cells to act as
      therapeutics in the field of biomedicine remains in the early stages; its
      efficacy is limited by the lack of innovative methodologies for chemokine
      presentation and release. This review describes how to direct the homing of
      endogenous stem cells via the administration of specific signals, with a
      particular emphasis on targeted signalling molecules that regulate this homing
      process, to enhance in situ tissue regeneration. We also provide an outlook on
      and critical considerations for future investigations to enhance stem cell
      recruitment and harness the reparative potential of these recruited cells as a
      clinically relevant cell therapy.

PMID- 28767195
TI  - Minimal dataset for post-registration surveillance of new drugs in hemophilia:
      communication from the SSC of the ISTH.

PMID- 28767193
TI  - Decreased hippocampal brain-derived neurotrophic factor and impaired cognitive
      function by hypoglossal nerve transection in rats.
AB  - The hypoglossal nerve controls tongue movements, and damages of it result in
      difficulty in mastication and food intake. Mastication has been reported to
      maintain hippocampus-dependent cognitive function. This study was conducted to
      examine the effect of tongue motor loss on the hippocampus-dependent cognitive
      function and its underlying mechanism. Male Sprague Dawley rats were subjected to
      the initial training of Morris water maze task before or after the bilateral
      transection of hypoglossal nerves (Hx). When the initial training was given
      before the surgery, the target quadrant dwelling time during the probe test
      performed at a week after the surgery was significantly reduced in Hx rats
      relative to sham-operated controls. When the initial training was given after the
      surgery, Hx affected the initial and reversal trainings and probe tests. Brain
      derived neurotrophic factor (BDNF) expression, cell numbers and long-term
      potentiation (LTP) were examined in the hippocampus on the 10th day, and BrdU and
      doublecortin staining on the 14th day, after the surgery. Hx decreased the
      hippocampal BDNF and cells in the CA1/CA3 regions and impaired LTP. BrdU and
      doublecortin staining was decreased in the dentate gyrus of Hx rats. Results
      suggest that tongue motor loss impairs hippocampus-dependent cognitive function,
      and decreased BDNF expression in the hippocampus may be implicated in its
      underlying molecular mechanism in relation with decreased
      neurogenesis/proliferation and impaired LTP.

PMID- 28767194
TI  - Echinacoside's nigrostriatal dopaminergic protection against 6-OHDA-Induced
      endoplasmic reticulum stress through reducing the accumulation of Seipin.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative diseases.
      Recent epidemiological studies suggest that echinacoside (ECH), a phenylethanoid
      glycoside found in Cistanche deserticola, has a protective effect against the
      development of PD. However, the detailed mechanisms of how ECH suppresses
      neuronal death have not been fully elucidated. In this study, we confirmed that
      ECH protects nigrostriatal neurons against 6-hydroxydopamine (6-OHDA)-induced
      endoplasmic reticulum stress (ERS) in vivo and in vitro. ECH rescued cell
      viability in damaged cells and decreased 6-OHDA-induced reactive oxygen species
      accumulation in vitro. It also rescued tyrosine hydroxylase and dopamine
      transporter expression in the striatum, and decreased alpha-synuclein aggregation
      following 6-OHDA treatment in vivo. The validated mechanism of ECH activity was
      the reduction in the 6-OHDA-induced accumulation of seipin (Berardinelli-Seip
      congenital lipodystrophy 2). Seipin has been shown to be a key molecule related
      to motor neuron disease and was tightly associated with ERS in a series of in
      vivo studies. ECH attenuated seipinopathy by promoting seipin degradation via
      ubiquitination. ERS was relieved by ECH through the Grp94/Bip-ATF4-CHOP signal
      pathway.

PMID- 28767196
TI  - Two unrelated children with overlapping 6q25.3 deletions, motor speech disorders,
      and language delays.
AB  - Interstitial and terminal 6q25 deletions are associated with developmental
      delays, hypotonia, eye pathologies, craniofacial dysmorphologies, and structural
      brain anomalies. In most cases, speech and language deficits are not described in
      detail. We report on a case (Patient 1, age 7 years) with a de novo 6q25.3-qter
      deletion, 11.1 Mb long and encompassing 108 genes, and a case (Patient 2, age 5
      years) with an inherited interstitial 6q25.3 deletion, located within Patient 1's
      deletion region and 403 kb long, the smallest 6q25 deletion reported to date.
      Both children have hypotonia, motor speech disorders, and expressive language
      delays. Patient 1's speech was characterized by childhood apraxia of speech (CAS)
      and dysarthria. Other findings include developmental delay, ataxic cerebral
      palsy, optic nerve dysplagia, and atypical brain morphologies regarding the
      corpus callosum and gyration patterns, a clinical profile that closely matches a
      previously reported case with a nearly identical deletion. Patient 2 had speech
      characterized by CAS and typical nonverbal processing abilities. His father, a
      carrier, had typical speech and language but showed difficulties with complex
      motor speech and hand motor tasks, similar to other adults with residual signs of
      CAS. The small deletion in this family contains the IGF2R-AIRN-SLC22A2-SLC22A3
      gene cluster, which is associated with imprinting and maternal-specific
      expression of Igf2R, Slc22a2, and Slc22a3 in mice, whereas imprinting in humans
      is a polymorphic trait. The shared phenotypes in the two patients might be
      associated with the deletion of the gene cluster.

PMID- 28767197
TI  - The Effect of Additives on the Early Stages of Growth of Calcite Single Crystals.
AB  - As crystallization processes are often rapid, it can be difficult to monitor
      their growth mechanisms. In this study, we made use of the fact that
      crystallization proceeds more slowly in small volumes than in bulk solution to
      investigate the effects of the soluble additives Mg2+ and poly(styrene sulfonate)
      (PSS) on the early stages of growth of calcite crystals. Using a "Crystal Hotel"
      microfluidic device to provide well-defined, nanoliter volumes, we observed that
      calcite crystals form via an amorphous precursor phase. Surprisingly, the first
      calcite crystals formed are perfect rhombohedra, and the soluble additives have
      no influence on the morphology until the crystals reach sizes of 0.1-0.5 MUm for
      Mg2+ and 1-2 MUm for PSS. The crystals then continue to grow to develop
      morphologies characteristic of these additives. These results can be rationalized
      by considering additive binding to kink sites, which is consistent with crystal
      growth by a classical mechanism.

PMID- 28767198
TI  - Optimal cut-off score of the Edinburgh Postnatal Depression Scale for major
      depressive episode during pregnancy in Japan.
AB  - AIM: Depression during pregnancy adversely affects both mother and child. As
      antenatal depression is a predictor of postnatal depression, early detection
      might prevent postnatal depression. The Edinburgh Postnatal Depression Scale
      (EPDS) is frequently used during the perinatal period, but the cut-off score
      during pregnancy has not been verified for the Japanese population. We aimed to
      clarify the optimal EPDS cut-off score in mid-pregnancy in Japan. METHODS: We
      recruited pregnant women aged 20 years or older at 12-24 gestational weeks and
      those who scored >=9 on the EPDS were invited to participate in this study. In
      parallel with the EPDS, the Japanese version of the Mini-International
      Neuropsychiatric Interview was administered to determine diagnosis of major
      depressive episode. We then calculated the receiver-operator curve, sensitivity
      and specificity, and positive and negative predictive values for the EPDS.
      RESULTS: All 210 participants were in the second trimester except for one (12
      gestational weeks). Twenty participants were diagnosed with major depressive
      episode. With a cut-off score set at 13 points, the area under the curve was
      0.956; sensitivity and specificity were 90.0% and 92.1% [Correction added on 10
      November 2017, after first online publication: The percentage for specificity has
      been corrected from 79.0% to 92.1%.], respectively; and positive and negative
      predictive values were 54.5% and 98.9%, respectively. CONCLUSION: To our
      knowledge, this is the first study to clarify the optimal EPDS cut-off score in
      the second trimester for Japan. This finding will be helpful for appropriate
      screening for antenatal depression in Japan.

PMID- 28767199
TI  - A model for prioritizing landfills for remediation and closure: A case study in
      Serbia.
AB  - The existence of large numbers of landfills that do not fulfill sanitary
      prerequisites presents a serious hazard for the environment in lower income
      countries. One of the main hazards is landfill leachate that contains various
      pollutants and presents a threat to groundwater. Groundwater pollution from
      landfills depends on various mutually interconnected factors such as the waste
      type and amount, the amount of precipitation, the landfill location
      characteristics, and operational measures, among others. Considering these
      factors, lower income countries face a selection problem where landfills urgently
      requiring remediation and closure must be identified from among a large number of
      sites. The present paper proposes a model for prioritizing landfills for closure
      and remediation based on multicriteria decision making, in which the hazards of
      landfill groundwater pollution are evaluated. The parameters for the
      prioritization of landfills are the amount of waste disposed, the amount of
      precipitation, the vulnerability index, and the rate of increase of the amount of
      waste in the landfill. Verification was performed using a case study in Serbia
      where all municipal landfills were included and 128 landfills were selected for
      prioritization. The results of the evaluation of Serbian landfills, prioritizing
      sites for closure and remediation, are presented for the first time. Critical
      landfills are identified, and prioritization ranks for the selected landfills are
      provided. Integr Environ Assess Manag 2018;14:105-119. (c) 2017 SETAC.

PMID- 28767200
TI  - Correlation between activated partial thromboplastin time and anti-Xa activity in
      patients who received low-molecular weight heparin as anticoagulation for
      haemodialysis.
AB  - Plasma anti-Xa activity, the recommended test to monitor low-molecular weight
      heparin (LMWH) therapy, is not readily available in many laboratories. In our
      clinical trials on the use of LMWH as anticoagulation for haemodialysis, a
      consistent prolongation of APTT in addition to the elevated anti-Xa activity was
      observed in the patients after LMWH administration. Hence, the paired anti-Xa
      activity and APTT data were re-analyzed. The APTT ratio, which was the
      proportional change in APTT from the baseline value after LMWH administration,
      was found to have a strong correlation with anti-Xa activity (coefficient of
      determination, R 2  = 0.72, P < 0.001). In the receiver operating characteristic
      analysis, the APTT ratio was also found to be an excellent predictor of
      therapeutic anti-Xa activity ?0.5 IU/mL (area under curve = 0.93, P < 0.001). The
      sensitivity was 88% and the specificity was 83.3% when an APTT ratio ?1.4 was
      used as the cut point to predict the achievement of therapeutic anti-Xa activity.
      Our results illustrated that APTT is a potentially useful screening test to
      assess the degree of anticoagulation achieved by LMWH during haemodialysis, if
      the testing for plasma anti-Xa activity is not available.

PMID- 28767202
TI  - Effects of parenteral fish oil on plasma nonesterified fatty acids and systemic
      inflammatory mediators in dogs following ovariohysterectomy.
AB  - OBJECTIVE: To evaluate the effects of intravenous (IV) infusion of fish oil (FO)
      emulsion following ovariohysterectomy (OVH) on inflammatory mediators and plasma
      omega-3 nonesterified fatty acids (NEFA) concentrations in dogs. DESIGN:
      Prospective clinical study. SETTING: University teaching hospital. ANIMALS:
      Twenty-nine privately owned dogs undergoing routine OVH. INTERVENTIONS:
      Postoperative 3-hour IV infusion of saline (n = 9), FO (Omegaven, n = 10), or
      soybean oil (SO, intralipid, n = 10) emulsion and blood collected before, 5 and
      24 hours following OVH for plasma NEFA and RBC membrane fatty acids (FAs)
      concentrations, leukocyte cytokine production capacity, and C-reactive protein
      (CRP) measurement. MEASUREMENTS AND MAIN RESULTS: Plasma omega-3 NEFA,
      eicosapentaenoic acid, docosahexaenoic acid, and total long-chain omega-3 FA
      significantly increased shortly after FO infusion (8.8 +/- 3.3 MUM, 13.6 +/- 5.6
      MUM, and 25.1 +/- 9.6 MUM, respectively) compared to SO (0.7 +/- 0.9, 2.3 +/-
      1.8, and 4.2 +/- 3.0 MUM, respectively) and saline infusion (1.6 +/- 2.5, 2.6 +/-
      3.1, and 5.9 +/- 6.4 MUM, respectively). Plasma CRP concentration significantly
      increased after OVH, but with no significant group differences. A weak negative
      correlation occurred between post-OVH CRP and postinfusion total long-chain omega
      3 FA concentrations (r2 = 0.21, P = 0.014). Stimulated leukocyte interleukin (IL)
      6 production capacity increased (P = 0.001) after OVH in all groups; SO infusion
      resulted in reduced leukocyte IL-6 production capacity (1048.1 +/- 277.7 pg/mL)
      compared to FO (1299.9 +/- 302.1 pg/mL, P = 0.048) and saline infusions (1499.0
      +/- 363.1 pg/mL, P = 0.01). No significant group difference was observed in
      leukocyte IL-10 and tumor necrosis factor alpha production capacities.
      CONCLUSIONS: Postoperative administration of FO emulsion increases plasma omega-3
      NEFA concentrations promptly, but does not significantly attenuate CRP production
      or leukocyte cytokine production capacity. FO infusion at the dosage used in the
      present study can be safely used in dogs, but it was not clearly beneficial in
      decreasing post-OVH indices of inflammation.

PMID- 28767201
TI  - The apolipoprotein A-I mimetic peptide, D-4F, restrains neointimal formation
      through heme oxygenase-1 up-regulation.
AB  - D-4F, an apolipoprotein A-I (apoA-I) mimetic peptide, possesses distinctly anti
      atherogenic effects. However, the biological functions and mechanisms of D-4F on
      the hyperplasia of vascular smooth muscle cells (VSMCs) remain unclear. This
      study aimed to determine its roles in the proliferation and migration of VSMCs.
      In vitro, D-4F inhibited VSMC proliferation and migration induced by ox-LDL in a
      dose-dependent manner. D-4F up-regulated heme oxygenase-1 (HO-1) expression in
      VSMCs, and the PI3K/Akt/AMP-activated protein kinase (AMPK) pathway was involved
      in these processes. HO-1 down-regulation with siRNA or inhibition with zinc
      protoporphyrin (Znpp) impaired the protective effects of D-4F on the oxidative
      stress and the proliferation and migration of VSMCs. Moreover, down-regulation of
      ATP-binding cassette transporter A1 (ABCA1) abolished the activation of Akt and
      AMPK, the up-regulation of HO-1 and the anti-oxidative effects of D-4F. In vivo,
      D-4F restrained neointimal formation and oxidative stress of carotid arteries in
      balloon-injured Sprague Dawley rats. And inhibition of HO-1 with Znpp decreased
      the inhibitory effects of D-4F on neointimal formation and ROS production in
      arteries. In conclusion, D-4F inhibited VSMC proliferation and migration in vitro
      and neointimal formation in vivo through HO-1 up-regulation, which provided a
      novel prophylactic and therapeutic strategy for anti-restenosis of arteries.

PMID- 28767203
TI  - Stress-Related Changes in Body Form: Results from the Whitehall II Study.
AB  - OBJECTIVE: Stress is associated with body mass gain in some people but with body
      mass loss in others. When the stressor persists, some people adapt with their
      stress responses, whereas others do not. Heart rate variability (HRV) reflects
      autonomic variability and is related to stress responses to psychosocial
      challenges. It was hypothesized that the combined effects of stress exposure and
      autonomic variability predict long-term changes in body form. METHODS: Data of
      1,369 men and 612 women from the Whitehall II cohort were analyzed. BMI, hip-to
      height ratio, and waist-to-height ratio were measured at three time points over a
      10-year period. HRV and psychological distress (General Health Questionnaire)
      were assessed. RESULTS: Men with high psychological distress were at risk of
      developing an increased waist-to-height ratio (F = 3.4, P = 0.038). Men with high
      psychological distress and low HRV were prone to develop an increased body mass
      and hip-to-height ratio (psychological distress: F = 4.3, P = 0.016; HRV: F =
      5.0, P = 0.008). Statistical trends showed that women displayed similar patterns
      of stress-related changes in body form (P = 0.061; P = 0.063). CONCLUSIONS:
      Assessing psychological distress and autonomic variability predicts changes in
      body form. Psychological distress was found to be associated with an increased
      risk of developing the wide-waisted phenotype, while psychological distress
      combined with low autonomic variability was associated with an increased risk of
      developing the corpulent phenotype.

PMID- 28767205
TI  - Prevalence and Pharmacotherapy of Behavioral and Psychological Symptoms of
      Dementia in a Geriatric Psychiatry Unit: A Retrospective Analysis.
AB  - Objective: To observe (1) the proportion and nature of behavioral and
      psychological symptoms of dementia (BPSD) in patients treated at a geriatric
      psychiatry ward in Germany over a time span of 1 year and (2) the use and effect
      of various pharmacologic interventions in managing BPSD in a real-world scenario.
      Methods: This study was a naturalistic, retrospective analysis. Between May 2015
      and May 2016, 437 patients aged 65 to 100 years with various psychiatric diseases
      (including dementia, schizophrenia, and depression) were admitted to a geriatric
      psychiatry unit in Germany. Their medical charts were reviewed to identify
      patients with dementia who presented with BPSD according to DSM-5 criteria. Since
      a decline in behavioral organization is a typical clinical manifestation of
      delirium, delirious patients with behavioral symptoms at admission were also
      included. Results: Of 437 patients, 74 (16.9%) showed severe behavioral symptoms
      that were categorized into 6 groups: aggression, screaming, wandering, food
      refusal, self-harm, and a combination of both behavioral and psychological
      symptoms. Overall, 65 patients (87.5%) showed improvement in their behavior
      regardless of the pharmacotherapy they were receiving. Conclusions: BPSD is one
      of the main reasons for admission to a geriatric psychiatry unit. Most of the
      patients with BPSD showed an improvement of behavioral symptoms with
      pharmacotherapy. Nonetheless, a clear correlation between a specific
      pharmacologic agent and behavioral improvement could not be established. A
      multimodal concept that involves both pharmacologic and nonpharmacologic
      approaches in managing BPSD should be the focus of future research.

PMID- 28767204
TI  - Blockade of myeloid differentiation protein 2 prevents obesity-induced
      inflammation and nephropathy.
AB  - Obesity is a major and independent risk factor of kidney diseases. The pathogenic
      mechanisms of obesity-associated renal injury are recognized to at least involve
      a lipid-rich and pro-inflammatory state of the renal tissues, but specific
      mechanisms establishing causal relation remain unknown. Saturated fatty acids are
      elevated in obesity, and known to induce chronic inflammation in kidneys. Myeloid
      differentiation protein 2 (MD2) is an important protein in lipopolysaccharide
      induced innate immunity response and inflammation. We suggested that obesity
      associated renal injury is regulated by MD2 thereby driving an inflammatory renal
      injury. The used three mouse models for in vivo study: MD2 knockout mice (KO)
      maintained on high fat diet (HFD), wild-type mice on HFD plus L6H21, a specific
      MD2 inhibitor and KO mice given palmitic acid (PA) by IV injection. The in vitro
      studies were carried out in cultured renal tubular epithelial cells, mouse
      mesangial cells and primary macrophages, respectively. The HFD mice presented
      with increased hyperlipidemia, serum creatinine and proteinuria. Renal tissue
      from HFD mice had increased fibrosis, inflammatory cytokines, macrophage
      infiltration, and activation of NF-kappaB and MAPKs. This HFD-induced renal
      injury profile was not observed in KO mice or L6H21-treated mice. Mice given PA
      mimmicked the HFD-induced renal injury profiles, which were prevented by MD2
      knockout. The in vitro data further confirmed MD2 mediates PA-induced
      inflammation. MD2 is causally related with obesity-associated renal inflammatory
      injury. We believe that MD2 is an attractive target for future therapeutic
      strategies in obesity-associated kidney diseases.

PMID- 28767206
TI  - Psychostimulant Use in Schizophrenia for Treatment of Negative Symptoms and
      Weight Loss.

PMID- 28767207
TI  - Paliperidone-Induced Hyponatremia.

PMID- 28767208
TI  - Lithium Use, but Not Valproate Use, Is Associated With a Higher Risk of Chronic
      Kidney Disease in Older Adults With Mental Illness.
AB  - OBJECTIVE: Lithium is an essential mood disorder treatment; however, it remains
      unclear whether lithium increases chronic kidney disease (CKD) risk. There are
      few data on this in the elderly, even though older adults may be particularly
      susceptible to CKD. We wished to determine whether lithium is associated with
      increased CKD risk relative to valproate in older adults. METHODS: This nested
      case-control study analyzed province-wide administrative health data from mental
      health service users aged >= 66 years in Ontario, Canada, from 2003 to 2014. Five
      year incident CKD risk was compared in lithium users, valproate users, and
      patients who used neither medication. ICD-10 was used to assign CKD diagnosis. We
      used conditional logistic regression to control for hypertension, diabetes
      mellitus, acute kidney injury, medications associated with lithium toxicity, and
      other potential confounders. RESULTS: 21,741 cases and 86,930 age- and sex
      matched controls were identified, including 529 lithium users and 498 valproate
      users. After controlling for confounders, we found that lithium use was
      associated with increased risk of incident CKD (adjusted odds ratio [OR] = 1.76
      [95% CI, 1.41-2.19]), while valproate use was not (adjusted OR = 1.03 [95% CI,
      0.81-1.29]). CONCLUSIONS: Lithium is independently associated with an almost 2
      fold increase in CKD risk in this community sample of older mental health service
      users. In the absence of clear information about certain contributing factors,
      such as inadequate monitoring and acute and chronic lithium level elevations,
      causes for this increase will need to be determined in future research.

PMID- 28767211
TI  - Graphene-Oxide-Assisted Synthesis of GaN Nanosheets as a New Anode Material for
      Lithium-Ion Battery.
AB  - As the most-studied III-nitride, theoretical researches have predicted the
      presence of gallium nitride (GaN) nanosheets (NSs). Herein, a facile synthesis
      approach is reported to prepare GaN NSs using graphene oxide (GO) as sacrificial
      template. As a new anode material of Li-ion battery (LIBs), GaN NSs anodes
      deliver the reversible discharge capacity above 600 mA h g-1 at 1.0 A g-1 after
      1000 cycles, and excellent rate performance at current rates from 0.1 to 10 A g
      1. These results not only extend the family of 2D materials but also facilitate
      their use in energy storage and other applications.

PMID- 28767209
TI  - Preventive Effects of Suvorexant on Delirium: A Randomized Placebo-Controlled
      Trial.
AB  - OBJECTIVE: No highly effective pharmacologic interventions to prevent delirium
      have been identified. We examined whether suvorexant, a potent and selective
      orexin receptor antagonist, is effective for the prevention of delirium. METHODS:
      We conducted a multicenter, rater-blinded, randomized, placebo-controlled
      clinical trial in intensive care units and regular acute wards between April 2015
      and March 2016. Eligible patients were 65 to 89 years old, newly admitted due to
      emergency, and able to take medicine orally and had an expected stay or life
      expectancy of 48 hours or more. Seventy-two patients were randomly assigned using
      the sealed envelope method to receive suvorexant (15 mg/d; 36 patients) or
      placebo (36 patients) every night for 3 days. The primary outcome measure was
      incidence of delirium as determined by the DSM-5. Trained psychiatrists assessed
      for delirium. RESULTS: We found that delirium developed significantly less often
      among patients taking suvorexant than among those taking placebo (0% [n/N = 0/36]
      vs 17% [6/36], respectively, P = .025). Comparison by log-rank test also showed
      that delirium developed significantly less often among patients taking suvorexant
      than among those taking placebo (chi2 = 6.46, P = .011). Analysis of variance
      revealed a tendency for main effect of treatment (F = 3.79, P = .053) on the
      sleep-wake cycle disturbance score (item 1) of the Japanese version of the
      Delirium Rating Scale-Revised-98 (DRS-R-98-J). There were no significant
      differences in adverse events. CONCLUSIONS: Suvorexant administered nightly to
      elderly patients admitted for acute care may provide protection against delirium.
      Larger studies are needed to show the potential of suvorexant to improve the
      circadian core domain of delirium. TRIAL REGISTRATION: UMIN Clinical Trials
      Registry identifier: UMIN000015681.

PMID- 28767212
TI  - Drawn on Paper: A Reproducible Humidity Sensitive Device by Handwriting.
AB  - This article describes the development of a kind of full carbon-based humidity
      sensor fabricated on the paper substrate by handwriting. The electrodes were
      written by commercial pencils, and the sensitive layer was drawn with an oxidized
      multiwalled carbon nanotubes (o-MWCNTs) ink marker. The resultant devices exhibit
      good reproducibility and stability during the dynamic measurement. The response
      of the optimized paper-based sensor exhibits about five times higher than sensors
      fabricated on the ceramic substrate, which is owing to the hydrophilic property
      of the paper substrate. The structure of the sensitive layer formed by dispersing
      sensitive materials in the porous surface of paper substrates alleviates the
      inner stress in the process of bending. The response of printing paper-based
      sensors only shows the 6.7% decay even under an extremely high bending degree.

PMID- 28767213
TI  - Synergistically Enhanced Electrochemical Performance of Ni3S4-PtX (X = Fe, Ni)
      Heteronanorods as Heterogeneous Catalysts in Dye-Sensitized Solar Cells.
AB  - Platinum (Pt)-based alloys are considerably promising electrocatalysts for the
      reduction of I-/I3- and Co2+/Co3+ redox couples in dye-sensitized solar cells
      (DSSCs). However, it is still challenging to minimize the dosage of Pt to achieve
      comparable or even higher catalytic efficiency. Here, by taking full advantages
      of the Mott-Schottky (M-S) effect at the metal-semiconductor interface, we
      successfully strategize a low-Pt-based M-S catalyst with enhanced
      electrocatalytic performance and stability for the large-scale application of
      DSSCs. The optimized M-S electrocatalyst of Ni3S4-Pt2X1 (X = Fe, Ni)
      heteronanorods is constructed by rationally controlling the ratio of Pt to
      transition metal in the hybrids. It was found that the electrons transferred from
      Ni3S4 to Pt2X1 at their interface under the Mott-Schottky effect result in the
      concentration of electrons onto Pt2X1 domains, which subsequently accelerates the
      regeneration of both I-/I3- and Co2+/Co3+ redox shuttles in DSSCs. As a result,
      the DSSC with Ni3S4-Pt2Fe1 manifests an impressive power conversion efficiency
      (PCE) of 8.79% and 5.56% for iodine and cobalt-based electrolyte under AM1.5G
      illumination, respectively. These PCEs are obviously superior over those with
      Ni3S4-Pt, PtFe, Ni3S4, and pristine Pt electrodes. The strategy reported here is
      able to be further expanded to fabricate other low-Pt-alloyed M-S catalysts for
      wider applications in the fields of photocatalysis, water splitting, and
      heterojunction solar cells.

PMID- 28767214
TI  - Light-Triggered Pyroelectric Nanogenerator Based on a pn-Junction for Self
      Powered Near-Infrared Photosensing.
AB  - A nanogenerator, as a self-powered system, can operate without an external power
      supply for energy harvesting, signal processing, and active sensing. Here, near
      infrared (NIR) photothermal triggered pyroelectric nanogenerators based on pn
      junctions are demonstrated in a p-Si/n-ZnO nanowire (NW) heterostructure for self
      powered NIR photosensing. The pyroelectric-polarization potential (pyro
      potential) induced within wurtzite ZnO NWs couples with the built-in electric
      field of the pn-junction. At the moment of turning on or off the NIR
      illumination, external current flow is induced by the time-varying internal
      electric field of the pn-heterostructure, which enables a bias-free operation of
      the photodetectors (PDs). The NIR PD exhibits a high on/off photocurrent ratio up
      to 107 and a fast photoresponse component with a rise time of 15 MUs and a fall
      time of 21 MUs. This work provides an unconventional strategy to achieve active
      NIR sensing, which may find promising applications in biological imaging,
      optoelectronic communications, and optothermal detections.

PMID- 28767215
TI  - The Deformations of Carbon Nanotubes under Cutting.
AB  - The determination of structural evolution at the atomic level is essential to
      understanding the intrinsic physics and chemistries of nanomaterials.
      Mechanochemistry represents a promising method to trace structural evolution, but
      conventional mechanical tension generates random breaking points, which makes it
      unavailable for effective analysis. It remains difficult to find an appropriate
      model to study shear deformations. Here, we synthesize high-modulus carbon
      nanotubes that can be cut precisely, and the structural evolution is efficiently
      investigated through a combination of geometry phase analysis and first
      principles calculations. The lattice fluctuation depends on the anisotropy,
      chirality, curvature, and slicing rate. The strain distribution further reveals a
      plastic breaking mechanism for the conjugated carbon atoms under cutting. The
      resulting sliced carbon nanotubes with controllable sizes and open ends are
      promising for various applications, for example, as an anode material for lithium
      ion batteries.

PMID- 28767216
TI  - Room-Temperature Fabrication of High-Performance Amorphous In-Ga-Zn-O/Al2O3 Thin
      Film Transistors on Ultrasmooth and Clear Nanopaper.
AB  - Integrating biodegradable cellulose nanopaper into oxide thin-film transistors
      (TFTs) for next generation flexible and green flat panel displays has attracted
      great interest because it offers a viable solution to address the rapid increase
      of electronic waste that poses a growing ecological problem. However, a
      compromise between device performance and thermal annealing remains an obstacle
      for achieving high-performance nanopaper TFTs. In this study, a high-performance
      bottom-gate IGZO/Al2O3 TFT with a dual-layer channel structure was initially
      fabricated on a highly transparent, clear, and ultrasmooth nanopaper substrate
      via conventional physical vapor deposition approaches, without further thermal
      annealing processing. Purified nanofibrillated cellulose with a width of
      approximately 3.7 nm was used to prepare nanopaper with excellent optical
      properties (92% transparency, 0.85% transmission haze) and superior surface
      roughness (Rq is 1.8 nm over a 5 * 5 MUm2 scanning area). More significantly, a
      bilayer channel structure (IGZO/Al2O3) was adopted to fabricate high performance
      TFT on this nanopaper substrate without thermal annealing and the device exhibits
      a saturation mobility of 15.8 cm2/(Vs), an Ion/Ioff ratio of 4.4 * 105, a
      threshold voltage (Vth) of -0.42 V, and a subthreshold swing (SS) of 0.66 V/dec.
      The room-temperature fabrication of high-performance IGZO/Al2O3 TFTs on such
      nanopaper substrate without thermal annealing treatment brings industry a step
      closer to realizing inexpensive, flexible, lightweight, and green paper displays.

PMID- 28767217
TI  - Synthesis and Physical Properties of Phase-Engineered Transition Metal
      Dichalcogenide Monolayer Heterostructures.
AB  - Heterostructures of transition metal dichalcogenides (TMDs) offer the attractive
      prospect of combining distinct physical properties derived from different TMD
      structures. Here, we report direct chemical vapor deposition of in-plane
      monolayer heterostructures based on 1H-MoS2 and 1T'-MoTe2. The large lattice
      mismatch between these materials led to intriguing phenomena at their interface.
      Atomic force microscopy indicated buckling in the 1H region. Tip-enhanced Raman
      spectroscopy showed mode structure consistent with Te substitution in the 1H
      region during 1T'-MoTe2 growth. This was confirmed by atomic resolution
      transmission electron microscopy, which also revealed an atomically stitched,
      dislocation-free 1H/1T' interface. Theoretical modeling revealed that both the
      buckling and absence of interfacial misfit dislocations were explained by lateral
      gradients in Te substitution levels within the 1H region and elastic coupling
      between 1H and 1T' domains. Phase field simulations predicted 1T' morphologies
      with spike-shaped islands at specific orientations consistent with experiments.
      Electrical measurements across the heterostructure confirmed its electrical
      continuity. This work demonstrates the feasibility of dislocation-free stitching
      of two different atomic configurations and a pathway toward direct synthesis of
      monolayer TMD heterostructures of different phases.

PMID- 28767218
TI  - Selective Binders of the Tandem Src Homology 2 Domains in Syk and Zap70 Protein
      Kinases by DNA-Programmed Spatial Screening.
AB  - Members of the Syk family of tyrosine kinases arrange Src homology 2 (SH2)
      domains in tandem to allow the firm binding of immunoreceptor tyrosine-based
      interaction motifs (ITAMs). While the advantages provided by the bivalency
      enhanced interactions are evident, the impact on binding specificity is less
      clear. For example, the spleen tyrosine kinase (Syk) and the zeta-chain
      associated protein kinase (ZAP-70) recognize the consensus sequence pYXXI/L(X)6-8
      pYXXI/L with near-identical nanomolar affinity. The nondiscriminatory
      recognition, on the one hand, poses a specificity challenge for the design of
      subtype selective protein binders and, on the other hand, raises the question as
      to how differential activation of Syk and ZAP-70 is ensured when both kinases are
      co-expressed. Herein, we identified the criteria for the design of binders that
      specifically address either the Syk or the Zap-70 tSH2 domain. Our approach is
      based on DNA-programmed spatial screening. Tyrosine-phosphorylated peptides
      containing the pYXXI/L motif were attached to oligonucleotides and aligned in
      tandem on a DNA template by means of nucleic acid hybridization. The distance
      between the pYXXI/L motifs and the orientation of strands were varied. The
      exploration exposed remarkably different recognition characteristics. While Syk
      tSH2 has a rather broad substrate scope, ZAP-70 tSH2 required a proximal
      arrangement of the phosphotyrosine ligands in defined strand orientation. The
      spatial screen led to the design of mutually selective, DNA-free binders, which
      discriminate Zap-70 and Syk tSH2 by 1 order of magnitude in affinity.

PMID- 28767219
TI  - Anomalous Ambipolar Transport of Organic Semiconducting Crystals via Control of
      Molecular Packing Structures.
AB  - Organic crystals deposited on 2-dimensional (2D) van der Waals substrates have
      been widely investigated due to their unprecedented crystal structures and
      electrical properties. van der Waals interaction between organic molecules and
      the substrate induces epitaxial growth of high quality organic crystals and their
      anomalous crystal morphologies. Here, we report on unique ambipolar charge
      transport of a "lying-down" pentacene crystal grown on a 2D hexagonal boron
      nitride van der Waals substrate. From in-depth analysis on crystal growth
      behavior and ultraviolet photoemission spectroscopy measurement, it is revealed
      that the pentacene crystal at the initial growth stage have a lattice-strained
      packing structure and unique energy band structure with a deep highest occupied
      molecular orbital level compared to conventional "standing-up" crystals. The
      lattice-strained pentacene few layers enable ambipolar charge transport in field
      effect transistors with balanced hole and electron field-effect mobilities.
      Complementary logic circuits composed of the two identical transistors show clear
      inverting functionality with a high gain up to 15. The interesting crystal
      morphology of organic crystals on van der Waals substrates is expected to attract
      broad attentions on organic/2D interfaces for their electronic applications.

PMID- 28767220
TI  - Engineering Intracellularly Retained Gaussia Luciferase Reporters for Improved
      Biosensing and Molecular Imaging Applications.
AB  - Gaussia luciferase (GLUC) is a bioluminescent reporter protein of increasing
      importance. As a secretory protein, it has increased sensitivity in vitro and in
      vivo (~20 000-fold, and ~1000-fold, respectively) over its competitor, secreted
      alkaline phosphatase. Unfortunately, this same advantageous secretory nature of
      GLUC limits its usefulness for many other possible intracellular applications,
      e.g., imaging signaling pathways in intact cells, in vivo imaging, and in
      developing molecular imaging biosensors to study protein-protein interactions and
      protein folding. Hence, to widen the research applications of GLUC, we developed
      engineered variants that increase its intracellular retention both by modifying
      the N-terminal secretory signal peptide and by tagging additional sequences to
      its C-terminal region. We found that when GLUC was expressed in mammalian cells,
      its N-terminal secretory signal peptide comprising amino acids 1-16 was essential
      for GLUC folding and functional activity in addition to its inherent secretory
      property. Modification of the C-terminus of GLUC by tagging a four amino acid
      (KDEL) endoplasmic reticulum targeting peptide in multiple repeats significantly
      improved its intracellular retention, with little impact on its folding and
      enzymatic activity. We used stable cells expressing this engineered GLUC with
      KDEL repeats to monitor chemically induced endoplasmic reticulum stress on cells.
      Additionally, we engineered an apoptotic sensor using modified variants of GLUC
      containing a four amino acid caspase substrate peptide (DEVD) between the GLUC
      protein and the KDEL repeats. Its use in cell culture resulted in increased GLUC
      secretion in the growth medium when cells were treated with the chemotherapeutic
      drugs doxorubicin, paclitaxel, and carboplatin. We thus successfully engineered a
      new variant GLUC protein that is retained inside cells rather than secreted
      extracellularly. We validated this novel reporter by incorporating it in
      biosensors for detection of cellular endoplasmic reticulum stress and caspase
      activation. This new molecularly engineered enzymatic reporter has the potential
      for widespread applications in biological research.

PMID- 28767221
TI  - Diffusion Bonding of Metal Wires Directly to the Functional Metal Oxide
      Semiconductors for Forming Reliable Electrical Contacts.
AB  - Forming reliable ohmic contacts to the functional metal oxide semiconductors has
      always been problematic in fabricating sensors and actuators. The common practice
      is to establish wire bonds to the metallic films previously deposited/printed
      over or under the oxide layer. Here, we describe a method for the diffusion
      bonding of metallic wire segments directly to the oxide layer surface, and
      demonstrate the reproducible formation of contacts with reliable mechanical and
      electrical qualities. Bonding is made at elevated temperatures in the 350-500 
      degrees C range under die pressure. Bonding Pt, Au, Ag, Cu, and Al wires to SnO2,
      TiO2, and ZnO are demonstrated.

PMID- 28767222
TI  - Assessing Different E3 Ligases for Small Molecule Induced Protein Ubiquitination
      and Degradation.
AB  - Proteolysis targeting chimera (PROTAC) technology, the recruitment of E3
      ubiquitin ligases to induce the degradation of a protein target, is rapidly
      impacting chemical biology, as well as modern drug development. Here, we explore
      the universality of this approach by evaluating different E3 ubiquitin ligases,
      engineered in their substrate binding domains to accept a recruiting ligand. Five
      out of six E3 ligases were found to be amenable to recruitment for target
      degradation. Taking advantage of the tight spatiotemporal control of inducing
      ubiquitination on a preselected target in living cells, we focused on two of the
      engineered E3 ligases, betaTRCP and parkin, to unravel their ubiquitination
      characteristics in comparison with the PROTAC-recruited endogenous E3 ligases VHL
      and cereblon.

PMID- 28767223
TI  - Plasmon-Induced Conductance Switching of an Electroactive Conjugated Polymer
      Nanojunction.
AB  - A plasmonic molecular electronic device, consisting of poly(3,4
      ethylenedioxythiophene) (PEDOT) nanowires bridging an ultramicroelectrode and an
      indium tin oxide (ITO) substrate covered by gold nanoparticles (Au NPs), has been
      developed. Light irradiation of this device has a dramatic impact on its
      conductance. Polymer strands, maintained electrochemically in their oxidized,
      conducting state, reversibly switch to their insulating state upon irradiation by
      visible-wavelength light, resulting in a sharp decrease in the conductance. The
      high-conductance state is restored when the light is turned off. Switching
      depends on the wavelength and the intensity of the incident light. It is due to
      reversible reduction of the nanosized region of PEDOT nanowires in contact with a
      gold NP and is attributed to plasmon-induced hot-electron injection into the
      PEDOT. The high/low conductance ratio can be as great as 1000, and switching
      requires low light intensity (220 W/m2). These results could open the way to the
      design of a new family of optoelectronic switches.

PMID- 28767224
TI  - Iminodiacetic Acid-Modified Human Serum Albumin: A Multifunctional Agent against
      Metal-Associated Amyloid beta-Protein Aggregation and Cytotoxicity.
AB  - Metal-induced amyloid beta-protein (Abeta) aggregation plays a key role in the
      pathogenesis of Alzheimer's disease. Although several agents have been recognized
      to block metal-associated Abeta aggregation, their therapeutic potential is
      marred due to the high-concentration metal ions in the amyloid plaques. To
      overcome this problem, we have herein developed iminodiacetic acid-modified human
      serum albumin (I-HSA) to fight against the aggregation. The multifunctional
      nature of I-HSA was extensively characterized in inhibiting the Abeta42
      aggregation associated with Zn2+ and Cu2+. The results revealed the following:
      (1) I-HSA significantly inhibited Abeta42 aggregation and alleviated its
      cytotoxicity. (2) I-HSA possessed a metal-chelate capacity as high as 31.2
      mol/mol, and 25 MUM I-HSA could effectively inhibit the influence of 250 MUM Zn2+
      on Abeta42 aggregation. (3) Equimolar I-HSA remarkably attenuated the reactive
      oxygen species damage caused by the Abeta42 and Cu2+-Abeta42 species. (4) I-HSA
      could remodel metal-Abeta42 fibrils into unstructured aggregates with less
      neurotoxicity. The cytotoxicity of mature Cu2+-Abeta42 aggregates was mitigated
      from 64.8% to 25.4% under the functioning of I-HSA. In conclusion, I-HSA showed
      prominent advantages for the high metal-chelate capacity. To our knowledge, I-HSA
      is the first multifunctional macromolecule for inhibiting high-concentration
      metal-induced Abeta42 aggregation and remodeling mature metal-induced Abeta42
      species.

PMID- 28767225
TI  - New Trends and Current Status of Positron-Emission Tomography and Single-Photon
      Emission Computerized Tomography Radioligands for Neuronal Serotonin Receptors
      and Serotonin Transporter.
AB  - The critical role of serotonin (5-hydroxytryptamine; 5-HT) and its receptors (5
      HTRs) in the pathophysiology of diverse neuropsychiatric and neurodegenerative
      disorders render them attractive diagnostic and therapeutic targets for brain
      disorders. Therefore, the in vivo assessment of binding of 5-HT receptor ligands
      under a multitude of physiologic and pathologic scenarios may support more
      accurate identification of disease and its progression and the patient's response
      to therapy as well as the screening of novel therapeutic strategies. The present
      Review aims to focus on the current status of radioligands used for positron
      emission tomography (PET) and single-photon-emission computerized tomography
      (SPECT) imaging of human brain serotonin receptors. We further elaborate upon and
      emphasize the attributes that qualify a radioligand for theranostics on the basis
      of its frequency of use in clinics, its benefit to risk assessment in humans, and
      its continuous evolution, along with the major limitations.

PMID- 28767226
TI  - Mussel-Inspired Architecture of High-Flux Loose Nanofiltration Membrane
      Functionalized with Antibacterial Reduced Graphene Oxide-Copper Nanocomposites.
AB  - Graphene-based nanocomposites have a vast potential for wide-ranging
      antibacterial applications due to the inherently strong biocidal activity and
      versatile compatibility of such nanocomposites. Therefore, graphene-based
      functional nanomaterials can introduce enhanced antibiofouling and antimicrobial
      properties to polymeric membrane surfaces. In this study, reduced graphene oxide
      copper (rGOC) nanocomposites were synthesized as newly robust biocides via in
      situ reduction. Inspired by the emerging method of bridging ultrafiltration
      membrane surface cavities, loose nanofiltration (NF) membranes were designed
      using a rapid (2 h) bioinspired strategy in which rGOC nanocomposites were firmly
      codeposited with polydopamine (PDA) onto an ultrafiltration support. A series of
      analyses (SEM, EDS, XRD, XPS, TEM, and AFM) confirmed the successful synthesis of
      the rGO-Cu nanocomposites. The secure loading of rGOC composites onto the
      membrane surfaces was also confirmed by SEM and AFM images. Water contact angle
      results display a high surface hydrophilicity of the modified membranes. The PDA
      rGOC functionalization layer facilitated a high water permeability (22.8 L m-2 h
      1 bar-1). The PDA-rGOC modification additionally furnished the membrane with
      superior separation properties advantageous for various NF applications such as
      dye purification or desalination, as ultrahigh (99.4% for 0.5 g L-1 reactive blue
      2) dye retention and high salt permeation (7.4% for 1.0 g L-1 Na2SO4, 2.5% for
      1.0 g L-1 NaCl) was achieved by the PDA-rGOC-modified membranes. Furthermore,
      after 3 h of contact with Escherichia coli (E. coli) bacteria, the rGOC
      functionalized membranes exhibited a strong antibacterial performance with a
      97.9% reduction in the number of live E. coli. This study highlights the use of
      rGOC composites for devising loose NF membranes with strong antibacterial and
      separation performance.

PMID- 28767227
TI  - Superior Flame-Resistant Cellulose Nanofibril Aerogels Modified with Hybrid Layer
      by-Layer Coatings.
AB  - Nanometer thin films consisting of cationic chitosan (Ch), anionic
      poly(vinylphosphonic acid) (PVPA), and anionic montmorillonite clay (MMT) are
      deposited on highly porous, wet-stabilized cellulose nanofibril (CNF) aerogels
      via the layer-by-layer (LbL) technique. Model experiments with silicon oxide
      surfaces are used to study the details of LbL formation and the multilayer
      structure. Formation of layers on the aerogels is also investigated as a function
      of solution concentration by use of polyelectrolyte titration. Thermogravimetric
      analysis indicates that the LbL coating significantly improves thermal stability
      of the CNF aerogel. Horizontal flame test shows that aerogels coated with five
      quadlayers of Ch/PVPA/Ch/MMT, using solutions/dispersion of high concentration,
      are able to self-extinguish immediately after removal of flame, and LbL-coated
      aerogels do not ignite under heat flux (35 kW/m2) in cone calorimetry. The LbL
      coated aerogel can prevent flame penetration from a torch focused on the surface,
      achieving temperature drops up to 650  degrees C across the 10 mm thick specimen
      for several minutes. LbL treatment is hence a rapid and highly effective way to
      specifically tailor the surface properties of CNF aerogels in order to confer
      unprecedented flame-retardant characteristics.

PMID- 28767229
TI  - Photochemical Water-Splitting with Organomanganese Complexes.
AB  - Certain organometallic chromophores with water-derived ligands, such as the known
      [Mn(CO)3(MU3-OH)]4 (1) tetramer, drew our attention as possible platforms to
      study water-splitting reactions. Herein, we investigate the UV irradiation of
      various tricarbonyl organomanganese complexes, including 1, and demonstrate that
      dihydrogen, CO, and hydrogen peroxide form as products in a photochemical water
      splitting decomposition reaction. The organic and manganese-containing side
      products are also characterized. Labeling studies with 18O-1 suggest that the
      source of oxygen atoms in H2O2 originates from free water that interacts with 1
      after photochemical dissociation of CO (1-CO) constituting the oxidative half
      reaction of water splitting mediated by 1. Hydrogen production from 1 is the
      result of several different processes, one of which involves the protons derived
      from the hydroxido ligands in 1 constituting the reductive half-reaction of water
      splitting mediated by 1. Other processes that generate H2 are also operative and
      are described. Collectively the results from the photochemical decomposition of 1
      provide an opportunity to propose a mechanism, and it is discussed within the
      context of developing new strategies for water-splitting reactions with
      organomanganese complexes.

PMID- 28767228
TI  - 89Zr-Immuno-Positron Emission Tomography in Oncology: State-of-the-Art 89Zr
      Radiochemistry.
AB  - Immuno-positron emission tomography (immunoPET) with 89Zr-labeled antibodies has
      shown great potential in cancer imaging. It can provide important information
      about the pharmacokinetics and tumor-targeting properties of monoclonal
      antibodies and may help in anticipating on toxicity. Furthermore, it allows
      accurate dose planning for individualized radioimmunotherapy and may aid in
      patient selection and early-response monitoring for targeted therapies. The most
      commonly used chelator for 89Zr is desferrioxamine (DFO). Preclinical studies
      have shown that DFO is not an ideal chelator because the 89Zr-DFO complex is
      partly unstable in vivo, which results in the release of 89Zr from the chelator
      and the subsequent accumulation of 89Zr in bone. This bone accumulation
      interferes with accurate interpretation and quantification of bone uptake on PET
      images. Therefore, there is a need for novel chelators that allow more stable
      complexation of 89Zr. In this Review, we will describe the most recent
      developments in 89Zr radiochemistry, including novel chelators and site-specific
      conjugation methods.

PMID- 28767230
TI  - Mechanistically Driven Development of an Iron Catalyst for Selective Syn
      Dihydroxylation of Alkenes with Aqueous Hydrogen Peroxide.
AB  - Product release is the rate-determining step in the arene syn-dihydroxylation
      reaction taking place at Rieske oxygenase enzymes and is regarded as a difficult
      problem to be resolved in the design of iron catalysts for olefin syn
      dihydroxylation with potential utility in organic synthesis. Toward this end, in
      this work a novel catalyst bearing a sterically encumbered tetradentate ligand
      based in the tpa (tpa = tris(2-methylpyridyl)amine) scaffold, [FeII(CF3SO3)2(5
      tips3tpa)], 1 has been designed. The steric demand of the ligand was envisioned
      as a key element to support a high catalytic activity by isolating the metal
      center, preventing bimolecular decomposition paths and facilitating product
      release. In synergistic combination with a Lewis acid that helps sequestering the
      product, 1 provides good to excellent yields of diol products (up to 97% isolated
      yield), in short reaction times under mild experimental conditions using a slight
      excess (1.5 equiv) of aqueous hydrogen peroxide, from the oxidation of a broad
      range of olefins. Predictable site selective syn-dihydroxylation of diolefins is
      shown. The encumbered nature of the ligand also provides a unique tool that has
      been used in combination with isotopic analysis to define the nature of the
      active species and the mechanism of activation of H2O2. Furthermore, 1 is shown
      to be a competent synthetic tool for preparing O-labeled diols using water as
      oxygen source.

PMID- 28767231
TI  - Correction to Screening Chemicals for Estrogen Receptor Bioactivity Using a
      Computational Model.

PMID- 28767232
TI  - RNA Polymerase Tags To Monitor Multidimensional Protein-Protein Interactions
      Reveal Pharmacological Engagement of Bcl-2 Proteins.
AB  - We report the development of a new technology for monitoring multidimensional
      protein-protein interactions (PPIs) inside live mammalian cells using split RNA
      polymerase (RNAP) tags. In this new system, a protein-of-interest is tagged with
      an N-terminal split RNAP (RNAPN), and multiple potential binding partners are
      each fused to orthogonal C-terminal RNAPs (RNAPC). Assembly of RNAPN with each
      RNAPC is highly dependent on interactions between the tagged proteins. Each PPI
      mediated RNAPN-RNAPC assembly transcribes from a separate promoter on a supplied
      DNA substrate, thereby generating a unique RNA output signal for each PPI. We
      develop and validate this new approach in the context of the Bcl-2 family of
      proteins. These key regulators of apoptosis are important cancer mediators, but
      are challenging to therapeutically target due to imperfect selectivity that leads
      to either off-target toxicity or tumor resistance. We demonstrate binary (1 * 1)
      and ternary (1 * 2) Bcl-2 PPI analyses by imaging fluorescent protein translation
      from mRNA outputs. Next, we perform a 1 * 4 PPI network analysis by direct
      measurement of four unique RNA signals via RT-qPCR. Finally, we use these new
      tools to monitor pharmacological engagement of Bcl-2 protein inhibitors, and
      uncover inhibitor-dependent competitive PPIs. The split RNAP tags improve upon
      other protein fragment complementation (PFC) approaches by offering both
      multidimensionality and sensitive detection using nucleic acid amplification and
      analysis techniques. Furthermore, this technology opens new opportunities for
      synthetic biology applications due to the versatility of RNA outputs for cellular
      engineering applications.

PMID- 28767233
TI  - "Polymultivalent" Polymer-Peptide Cluster Conjugates for an Enhanced Targeting of
      Cells Expressing alphavbeta3 Integrins.
AB  - A new class of "polymultivalent" ligands combining several ligand clusters and a
      water-soluble biocompatible polymer is introduced. These original conjugates bear
      two levels of multivalency. They are prepared by covalent coupling of a
      controlled number of tetrameric cRGD peptide clusters along a well-defined
      copolymer synthesized by RAFT polymerization. The presence of multiple copies of
      peptide clusters on the same polymer backbone resulted in a much-higher relative
      potency than the free cluster reference. Thanks to the "polymultivalency", up to
      ~2 orders of magnitude potency enhancement was reached in a competitive cell
      adhesion assay (nanomolar-range IC50 values). In addition, confocal microscopy
      and flow cytometry demonstrated that fluorescent "polymultivalent" conjugates
      (emitting in the far-red/near-infrared region) were able to specifically and
      selectively label cells expressing alphavbeta3-integrin, the natural receptor of
      cRGD.

PMID- 28767234
TI  - Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of
      Adenylate Kinase.
AB  - Crystal structures of adenylate kinase (AdK) from Escherichia coli capture two
      states: an "open" conformation (apo) obtained in the absence of ligands and a
      "closed" conformation in which ligands are bound. Other AdK crystal structures
      suggest intermediate conformations that may lie on the transition pathway between
      these two states. To characterize the transition from open to closed states in
      solution, X-ray solution scattering data were collected from AdK in the apo form
      and with progressively increasing concentrations of five different ligands.
      Scattering data from apo AdK are consistent with scattering predicted from the
      crystal structure of AdK in the open conformation. In contrast, data from AdK
      samples saturated with Ap5A do not agree with that calculated from AdK in the
      closed conformation. Using cluster analysis of available structures, we selected
      representative structures in five conformational states: open, partially open,
      intermediate, partially closed, and closed. We used these structures to estimate
      the relative abundances of these states for each experimental condition. X-ray
      solution scattering data obtained from AdK with AMP are dominated by scattering
      from AdK in the open conformation. For AdK in the presence of high concentrations
      of ATP and ADP, the conformational ensemble shifts to a mixture of partially open
      and closed states. Even when AdK is saturated with Ap5A, a significant proportion
      of AdK remains in a partially open conformation. These results are consistent
      with an induced-fit model in which the transition of AdK from an open state to a
      closed state is initiated by ATP binding.

PMID- 28767235
TI  - Tracking Hole Transport in DNA Hairpins Using a Phenylethynylguanine Nucleobase.
AB  - The hole transport dynamics of DNA hairpins possessing a stilbene electron
      acceptor and donor along with a modified guanine (G) nucleobase, specifically 8
      (4'-phenylethynyl)deoxyguanosine, or EG, have been investigated. The nearly
      indistinguishable oxidation potentials of EG and G and unique spectroscopic
      characteristics of EG+* make it well-suited for directly observing transient hole
      occupation during charge transport between a stilbene electron donor and
      acceptor. In contrast to the cation radical G+*, EG+* possesses a strong
      absorption near 460 nm and has a distinct Raman-active ethynyl stretch. Both
      spectroscopic characteristics are easily distinguished from those of the stilbene
      donor/acceptor radical ion chromophores. Employing EG, we observe its role as a
      shallow hole trap, or as an intermediate hole transport site when a deeper trap
      state is present. Using a combination of ultrafast absorption and stimulated
      Raman spectroscopies, the hole-transport dynamics are observed to be similar in
      systems having EG vs G bases, with small perturbations to the charge transport
      rates and yields. These results show EG can be deployed at specified locations
      throughout the sequence to report on hole occupancy, thereby enabling detailed
      monitoring of the hole transport dynamics with base-site specificity.

PMID- 28767236
TI  - Bioinstructive Coatings for Hematopoietic Stem Cell Expansion Based on Chemical
      Vapor Deposition Copolymerization.
AB  - We report the chemical vapor deposition (CVD) of dual-functional polymer films
      for the specific and orthogonal immobilization of two biomolecules (notch ligand
      delta-like 1 (DLL1) and an RGD-peptide) that govern the fate of hematopoietic
      stem and progenitor cells. The composition of the CVD polymer and thus the
      biomolecule ratio can be tailored to investigate and optimize the influence of
      the relative surface concentrations of biomolecules on stem cell behavior. Prior
      to cell experiments, all surfaces were characterized by infrared reflection
      adsorption spectroscopy, time-of-flight secondary ion mass spectrometry, and X
      ray photoelectron spectroscopy to confirm the presence of both biomolecules. In a
      proof-of-principle stem cell culture study, we show that all polymer surfaces are
      cytocompatible and that the proliferation of the hematopoietic stem and
      progenitor cells is predominantly influenced by the surface concentration of
      immobilized DLL1.

PMID- 28767237
TI  - Heterogeneous Organophosphate Ethanolysis: Degradation of Phosphonothioate
      Neurotoxin by a Supported Molybdenum Peroxo Polymer.
AB  - A polystyrene-supported molybdenum peroxo material [Mo-Y(s)] was applied toward
      the oxidative degradation of the organophosphate neurotoxin O,S-diethylphenyl
      phosphonothioate (1) through ethanolysis. In addition to the operational
      advantages of the heterogeneous reactivity, oxidative ethanolysis with a 10-fold
      excess of hydrogen peroxide yields only P-S bond scission to produce
      diethylphenyl phosphonate and ethyl sulfate. This is the first report of a
      molybdenum solid support that promotes the degradation of sulfur-containing
      organophosphate with the turnover benefits of heterogeneous catalysis. The
      activation parameters of 1 ethanolysis by Mo-Y(s) (Ea = 57 +/- 6 kJ/mol and
      DeltaS? = -124 +/- 21 J/mol.K) and by the model compound oxodiperoxo(pyridine-2
      carboxylato)molybdate(VI) bis(pyridine-2-carboxylic acid) monohydrate (3; Ea = 55
      +/- 5 kJ/mol and DeltaS? = -154 +/- 15 J/mol.K) are almost identical for the
      oxidation of thioanisole by 3. This suggests that the rate-determining step for 1
      ethanolysis is sulfur oxidation to form an intermediate phosphonothioate S-oxide,
      which subsequently undergoes nucleophilic attack by the ethanol solvent to form
      diethylphenyl phosphonate and ethyl sulfate. Evidence for the formation of this S
      oxide intermediate and the postulated ethanolysis mechanism is provided.

PMID- 28767238
TI  - Response to Comment on "Rapid Selective Circumneutral Degradation of Phenolic
      Pollutants Using Peroxymonosulfate-Iodide Metal-Free Oxidation: Role of Iodine
      Atoms".

PMID- 28767240
TI  - Polarizable Embedding Approach for the Analytical Calculation of Raman and Raman
      Optical Activity Spectra of Solvated Systems.
AB  - We present an analytical formulation and implementation of Raman and Raman
      Optical Activity (ROA) spectra within a three-layer fully polarizable Quantum
      Mechanical (QM)/ Molecular Mechanics (MM)/Polarizable Continuum Model (PCM)
      approach. Polarization effects in the MM layer are modeled by exploiting the
      Fluctuating Charges (FQ) method, in which MM solvent atoms are endowed with
      electric charges that can be mutually polarized by the solute QM density. Because
      of its fully polarizable atomistic description, QM/FQ/PCM is able to account for
      specific solvent effects like those due to hydrogen bonds, providing a physical
      picture for protic solvents such as water. Applications to aqueous (R)
      methyloxirane and (S)-methyllactate are presented, and results are compared with
      available experimental data.

PMID- 28767239
TI  - Zein Nanoparticles Uptake and Translocation in Hydroponically Grown Sugar Cane
      Plants.
AB  - The main objective of this study was to investigate the uptake and translocation
      of positively charged zein nanoparticles (ZNPs) in hydroponically grown sugar
      cane plants. Fluorescent ZNPs (spherical and measuring an average diameter 135 +/
      3 nm) were synthesized by emulsion-diffusion method from FITC-tagged zein.
      Fluorescent measurement following digestion of plant tissue indicated that sugar
      cane roots had a significant adhesion of ZNPs, 342.5 +/- 24.2 MUg NPs/mg of dry
      matter, while sugar cane leaves contained a very limited amount, 12.9 +/- 1.2 MUg
      NPs/mg dry matter for high dose(1.75 mg/ml) after 12 h. Confocal microscopy
      studies confirmed presence of fluorescent ZNPs in the epidermis and endodermis of
      the root system. Given their ability to adhere to roots for extended periods of
      time, ZNPs are proposed as effective delivery systems for agrochemicals to sugar
      cane plants, but more studies are needed to identify effect of nanoparticle
      exposure to health of the plant.

PMID- 28767241
TI  - Asymmetric Total Synthesis of (-)-Astakolactin and Confirmation of Its
      Stereostructure.
AB  - The originally proposed structure of astakolactin was revised, and an asymmetric
      total synthesis of the newly proposed structure was achieved. The key
      transformations in the synthesis were a Johnson-Claisen rearrangement, an
      asymmetric Mukaiyama aldol reaction, and a Mitsunobu-type cyclodehydration. The
      spectroscopic data and specific rotation of the compound obtained matched well
      with those reported for naturally occurring astakolactin.

PMID- 28767242
TI  - Ethylene Control Technologies in Extending Postharvest Shelf Life of Climacteric
      Fruit.
AB  - Fresh fruit is important for a healthy diet. However, because of their seasonal
      production, regional specific cultivation, and perishable nature, it is essential
      to develop preservation technologies to extend the postharvest shelf life of
      fresh fruits. Climacteric fruit adopt spoilage because of ethylene, a key hormone
      associated with the ripening process. Therefore, controlling ethylene activity by
      following safe and effective approaches is a key to extend the postharvest shelf
      life of fruit. In this review, ethylene control technologies will be discussed
      aiming for the need of developing more innovative and effective approaches. The
      biosynthesis pathway will be given first. Then, the technologies determining the
      postharvest shelf life of climacteric fruit will be described with special
      attention to the latest and significant published works in this field. Special
      attention is given to 1-methylcyclopropene (1-MCP), which is effective in fruit
      preservation technologies. Finally, the encapsulation technology to improve the
      stability of 1-MCP will be proposed, using a potential encapsulation agent of 1
      MCP, calixarene.

PMID- 28767243
TI  - Occurrence of Different Resistance Mechanisms to Acetolactate Synthase Inhibitors
      in European Sorghum halepense.
AB  - Four Hungarian and two Italian Sorghum halepense populations harvested in maize
      fields were investigated to elucidate the levels and mechanisms underlying
      acetolactate synthase (ALS) inhibitors resistance. The two Italian populations
      were highly cross-resistant to all ALS inhibitors tested, and the variant ALS
      allele Leu574 was identified in most of the plants; no differences were observed
      when the plants were treated with herbicide plus malathion. This suggests that
      the main resistance mechanism is target-site mediated. The Hungarian populations
      proved to be controlled by imazamox, while they were resistant to sulfonylureas
      and bispyribac-Na. All Hungarian populations, but not all plants of population 12
      49H, presented the variant allele Glu376. This is the first documented occurrence
      of the Asp-376-Glu substitution in S. halepense. ALS enzyme bioassay and
      treatment with malathion confirmed that at least in plants of two populations the
      resistance is very likely due to both target-site and enhanced metabolism of P450
      enzymes.

PMID- 28767244
TI  - Alkyl-Thiol Ligand-Induced Shape- and Crystalline Phase-Controlled Synthesis of
      Stable Perovskite-Related CsPb2Br5 Nanocrystals at Room Temperature.
AB  - Controlled synthesis of colloidal all-inorganic lead halide perovskite
      semiconductor nanocrystals, such as CsPbBr3, with tunable size, shape,
      composition, and crystalline phase have recently attracted wide interest for
      photonic and optoelectronic applications. Herein, we report a new strategy for
      using alkyl-thiols to induce the transformation of CsPbBr3 to perovskite-related
      cesium lead halide (CsPb2Br5) with controlled morphology and a crystalline phase
      at room temperature. By rational tuning the ratios of the alkyl-thiol ligands to
      alkyl-amines or to alkyl-acids, the as-synthesized colloidal nanocrystals can be
      rationally controlled from orthorhombic crystalline-phase CsPbBr3 to tetragonal
      phase CsPb2Br5 nanosheets and nanowires with high yield. Significantly, the
      tetragonal CsPb2Br5 nanowires and nanosheets have high stability in high
      temperature and high-humidity environments. These findings may open new
      directions for large-scale synthesis of shape- and crystalline phase-controlled
      perovskite nanocrystals for high-performance, low-cost optical electronic and
      optoelectronic devices.

PMID- 28767245
TI  - Direct Observation of Ultrafast Hole Injection from Lead Halide Perovskite by
      Differential Transient Transmission Spectroscopy.
AB  - Efficient charge separation at the interfaces of the perovskite with the carrier
      transport layers is crucial for perovskite solar cells to achieve high power
      conversion efficiency. We present a systematic experimental study on the hole
      injection dynamics from MAPbI3 perovskite to three typical hole transport
      materials (HTMs). We extract the carrier dynamics directly related to the hole
      injection by employing a pump light with short absorption depth and comparing the
      transient transmission signals excited on the two sides of the sample. The
      differential transmission signals reveal the hole injections to PTAA and
      PEDOT:PSS to be complete within 1 and 2 ps, respectively, and that to NiOx to
      exhibit an additional slow process on a 40 ps time scale. The obtained injection
      dynamics are discussed in comparison with the device performance of the solar
      cells containing the same MAPbI3/HTM interfaces.

PMID- 28767246
TI  - Comparative Study of the Effect of Defects on Selective Adsorption of Butanol
      from Butanol/Water Binary Vapor Mixtures in Silicalite-1 Films.
AB  - A promising route for sustainable 1-butanol (butanol) production is ABE (acetone,
      butanol, ethanol) fermentation. However, recovery of the products is challenging
      because of the low concentrations obtained in the aqueous solution, thus
      hampering large-scale production of biobutanol. Membrane and adsorbent-based
      technologies using hydrophobic zeolites are interesting alternatives to
      traditional separation techniques (e.g., distillation) for energy-efficient
      separation of butanol from aqueous mixtures. To maximize the butanol over water
      selectivity of the material, it is important to reduce the number of hydrophilic
      adsorption sites. This can, for instance, be achieved by reducing the density of
      lattice defect sites where polar silanol groups are found. The density of silanol
      defects can be reduced by preparing the zeolite at neutral pH instead of using
      traditional synthesis solutions with high pH. In this work, binary adsorption of
      butanol and water in two silicalite-1 films was studied using in situ attenuated
      total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy under equal
      experimental conditions. One of the films was prepared in fluoride medium,
      whereas the other one was prepared at high pH using traditional synthesis
      conditions. The amounts of water and butanol adsorbed from binary vapor mixtures
      of varying composition were determined at 35 and 50  degrees C, and the
      corresponding adsorption selectivities were also obtained. Both samples showed
      very high selectivities (100-23 000) toward butanol under the conditions studied.
      The sample having low density of defects, in general, showed ca. a factor 10
      times higher butanol selectivity than the sample having a higher density of
      defects at the same experimental conditions. This difference was due to a much
      lower adsorption of water in the sample with low density of internal defects.
      Analysis of molecular simulation trajectories provides insights on the local
      selectivities in the zeolite channel network and at the film surface.

PMID- 28767247
TI  - Enhanced Second-Harmonic Generation from Sequential Capillarity-Assisted Particle
      Assembly of Hybrid Nanodimers.
AB  - We show enhanced second-harmonic generation (SHG) from a hybrid metal-dielectric
      nanodimer consisting of an inorganic perovskite nanoparticle of barium titanate
      (BaTiO3) coupled to a metallic gold (Au) nanoparticle. BaTiO3-Au nanodimers of
      100 nm/80 nm sizes are fabricated by sequential capillarity-assisted particle
      assembly. The BaTiO3 nanoparticle has a noncentrosymmetric crystalline structure
      and generates bulk SHG. We use the localized surface plasmon resonance of the
      gold nanoparticle to enhance the SHG from the BaTiO3 nanoparticle. We
      experimentally measure the nonlinear signal from assembled nanodimers and
      demonstrate an up to 15-fold enhancement compared to a single BaTiO3
      nanoparticle. We further perform numerical simulations of the linear and SHG
      spectra of the BaTiO3-Au nanodimer and show that the gold nanoparticle acts as a
      nanoantenna at the SHG wavelength.

PMID- 28767248
TI  - Spreading Dynamics of Molten Polymer Drops on Glass Substrates.
AB  - Wetting dynamics drive numerous processes involving liquids in contact with solid
      substrates with a wide range of geometries. The spreading dynamics of organic
      liquids and liquid metals at, respectively, room temperature and >1000  degrees C
      have been studied extensively, both experimentally and numerically; however,
      almost no attention has been paid to the wetting behavior of molten drops of
      thermoplastic polymers, despite its importance, for example, in the processing of
      fiber-reinforced polymer composites. Indeed, the ability of classical theories of
      dynamic wetting, that is, the hydrodynamic and the molecular-kinetic theories, to
      model these complex liquids is unknown. We have therefore investigated the
      spreading dynamics on glass, over temperatures between 200 and 260  degrees C, of
      two thermoplastics: polypropylene (PP) and poly(vinylidene fluoride) (PVDF). PP
      and PVDF showed, respectively, the highest and lowest slip lengths due to their
      different interactions with the glass substrate. The jump lengths of PP and PVDF
      are comparable to their Kuhn segment lengths, suggesting that the wetting process
      of these polymers is mediated by segmental displacements. The present work not
      only provides evidence of the suitability of the classical models to model
      dynamic wetting of molten polymers but also advances our understanding of the
      wetting dynamics of molten thermoplastics at the liquid/solid interface.

PMID- 28767249
TI  - Fluorescent Quantum Dots Make Feasible Long-Range Transmission of Molecular Bits.
AB  - The modeling and realization of an effective communication platform for long
      range information transfer is reported. Messages are encrypted in molecular bits
      by concentration pulses of fluorescent carbon quantum dots having self-quenching
      emission that dynamically depends on the concentration pulses. Messages are
      transferred along longer paths when received and decoded by means of dynamical
      emission response with respect to the ones encoded by absorbance scaling linearly
      with messenger concentration. These results represent a significant breakthrough
      in view of the futuristic development of a nonspecific molecular communication
      platform to encode and transfer information in multiple fluid environments,
      ranging from physiological to industrial ones.

PMID- 28767250
TI  - Insights into the Impact of Surface Hydrophobicity on Droplet Coalescence and
      Jumping Dynamics.
AB  - Droplet coalescence jumping on superhydrophobic surfaces attracts much research
      attention owing to its capability in enhancing condensation for energy and water
      applications. In this work, we reveal the impact of the finite surface adhesion
      to explain velocity discrepancies observed in recent droplet jumping studies,
      particularly when droplet sizes are a few micrometers (1-10 MUm). Surface
      adhesion, which is usually neglected, can significantly affect both droplet
      coalescence and departure dynamics. It causes oscillations on velocity and
      contact area in the droplet coalescence process, as observed numerically and
      experimentally. Comparing the increasing rate of jumping velocity with contact
      angle for three different droplet sizes, we show that smaller droplets exhibit
      higher sensitivity to the change of surface hydrophobicity. We also specify the
      range of surface superhydrophobicity where the jumping velocity monotonically
      decreases (theta ? 170 degrees ), increases (theta ? 160 degrees ), or changes
      non-monotonically in transition (160 degrees  ? theta ?170 degrees ) with droplet
      size. As a result, there exists a broad jumping velocity range for micrometer
      sized droplets on a superhydrophobic surface with a slight contact angle
      variation. This work offers an extended understanding of the droplet coalescence
      and jumping dynamics to resolve the discrepancies in recent experimental
      observations.

PMID- 28767251
TI  - Role of Absorbing Nanocrystal Cores in Soft Photonic Crystals: A Spectroscopy and
      SANS Study.
AB  - Periodic superstructures of plasmonic nanoparticles have attracted significant
      interest because they can support coupled plasmonic modes, making them
      interesting for plasmonic lasing, metamaterials, and as light-management
      structures in thin-film optoelectronic devices. We have recently shown that noble
      metal hydrogel core-shell colloids allow for the fabrication of highly ordered 2
      dimensional plasmonic lattices that show surface lattice resonances as the result
      of plasmonic/diffractive coupling (Volk, K.; Fitzgerald, J. P. S.; Ruckdeschel,
      P.; Retsch, M.; Konig, T. A. F.; Karg, M. Reversible Tuning of Visible Wavelength
      Surface Lattice Resonances in Self-Assembled Hybrid Monolayers. Adv. Optical
      Mater. 2017, 5, 1600971, DOI: 10.1002/adom.201600971). In the present work, we
      study the photonic properties and structure of 3-dimensional crystalline
      superstructures of gold hydrogel core-shell colloids and their pitted
      counterparts without gold cores. We use far-field extinction spectroscopy to
      investigate the optical response of these superstructures. Narrow Bragg peaks are
      measured, independently of the presence or absence of the gold cores. All
      crystals show a significant reduction in low-wavelength scattering. This leads to
      a significant enhancement of the plasmonic properties of the samples prepared
      from gold-nanoparticle-containing core-shell colloids. Plasmonic/diffractive
      coupling is not evident, which we mostly attribute to the relatively small size
      of the gold cores limiting the effective coupling strength. Small-angle neutron
      scattering is applied to study the crystal structure. Bragg peaks of several
      orders clearly assignable to an fcc arrangement of the particles are observed for
      all crystalline samples in a broad range of volume fractions. Our results
      indicate that the nanocrystal cores do not influence the overall crystallization
      behavior or the crystal structure. These are important prerequisites for future
      studies on photonic materials built from core-shell particles, in particular, the
      development of new photonic materials from plasmonic nanocrystals.

PMID- 28767252
TI  - Criegee Intermediates React with Levoglucosan on Water.
AB  - Levoglucosan (Levo), a C6-anhydrosaccharide produced in the combustion of
      cellulosic materials, is the major component of aerosols produced from biomass
      burning over vast regions worldwide. Levo has long been considered chemically
      inert and thus has been used as a tracer of biomass burning sources. However, we
      now show that sugars including Levo, glucose, arabitol, and mannitol react
      rapidly with Criegee intermediates (CIs) generated during the ozonolysis of
      sesquiterpenes on the surface of water:acetonitrile microjets. Hydrophilic Levo
      reacts faster with CIs than with water or surface-active 1-octanol at air-aqueous
      interfaces. This unexpected phenomenon is likely associated with the relatively
      low water density at air-aqueous interfaces coupled with a higher gas-phase
      acidity of the saccharide hydroxyl groups (i.e., -OH) versus n-alkanols. Results
      presented herein show that aerosol saccharides are in fact reactive toward CIs.
      Given the abundance of saccharides in the atmosphere, they may be important
      contributors to the growth and mass loading of secondary organic aerosols.

PMID- 28767253
TI  - Synthesis of Aminophenanthrenes and Benzoquinolines via Hauser-Kraus Annulation
      of Sulfonyl Phthalide with Rauhut-Currier Adducts of Nitroalkenes.
AB  - The Hauser-Kraus reaction of sulfonyl phthalide with nitroalkene derivatives
      provides access to aminophenanthrenes, including phenanthrene-substituted amino
      acids and benzoquinolines. The intermediate quinones bearing a key ketoalkyl
      moiety undergoes facile intramolecular enamine cyclization. Interestingly,
      enamines derived from primary and secondary amines undergo cyclization via C
      centered nucleophilic attack to provide aminophenanthrenes, whereas those derived
      from ammonia undergo cyclization via N-centered nucleophilic attack leading to
      benzoquinolines. A one-pot protocol for the direct transformation of phthalides
      and nitroalkene derivatives to aminophenanthrenes and benzoquinolines has also
      been developed.

PMID- 28767254
TI  - Variability in Mass Spectrometry-based Quantification of Clinically Relevant Drug
      Transporters and Drug Metabolizing Enzymes.
AB  - Many different methods are used for mass-spectrometry-based protein
      quantification in pharmacokinetics and systems pharmacology. It has not been
      established to what extent the results from these various methods are comparable.
      Here, we compared six different mass spectrometry-based proteomics methods by
      measuring the expression of clinically relevant drug transporters and
      metabolizing enzymes in human liver. Mean protein concentrations were in general
      quantified to similar levels by methods using whole tissue lysates. Methods using
      subcellular membrane fractionation gave incomplete enrichment of the proteins.
      When the enriched proteins were adjusted to levels in whole tissue lysates, they
      were on average 4-fold lower than those quantified directly in whole tissue
      lysates. The differences in protein levels were propagated into differences in
      predictions of hepatic clearance. In conclusion, caution is needed when comparing
      and applying quantitative proteomics data obtained with different methods,
      especially since membrane fractionation is common practice for protein
      quantification used in drug clearance predictions.

PMID- 28767255
TI  - Viscosity and Conductivity Tunable Diode-like Behavior for Meso- and Micropores.
AB  - Rectifying pores, which transport ions mainly in one direction blocking the ionic
      flow in the other, were shown to be important in the preparation of chemical
      sensors, components of ionic circuits, and mimics of biological channels. Ionic
      rectification has been shown with various engineered systems, but pores with
      similar opening diameters often rectify to a various uncontrolled extent. In this
      Letter we present a system of single meso-pores, whose current-voltage curves and
      rectification can be tuned with great precision via viscosity and conductivity
      gradients of solutions placed on both sides of the membrane. The mechanism of
      rectification is based on electroosmotically induced flow, which fills the entire
      volume of the pore with a single solution from either side of the membrane. The
      highly predictable rectifying system can find various applications, including
      measuring viscosity of unknown media and tuning electrokinetic passage of
      particles.

PMID- 28767256
TI  - Correction to "Mesostructure of Mesoporous Silica/Anodic Alumina Hierarchical
      Membranes Tuned with Ethanol".

PMID- 28767257
TI  - Memory of Electric Field in Laponite and How It Affects Crack Formation: Modeling
      through Generalized Calculus.
AB  - Desiccation crack formation is affected by the presence of electric fields. We
      show here that the field effect not only is at work while the power supply is on
      but also leaves a memory even after switching off. The time required for the
      first appearance of cracks is shown to depend on the voltage of the field as well
      as the time duration of exposure. We model the system as a leaky capacitor
      described by a fractional order derivative in the constitutive equation. This
      gives a good fit to experimental data and explains the memory effect.

PMID- 28767258
TI  - Biexciton Resonances Reveal Exciton Localization in Stacked Perovskite Quantum
      Wells.
AB  - Quasi-two-dimensional lead halide perovskites, MAn-1PbnX3n+1, are quantum
      confined materials with an ever-developing range of optoelectronic device
      applications. Like other semiconductors, the correlated motion of electrons and
      holes dominates the material's response to optical excitation influencing its
      electrical and optical properties such as charge formation and mobility. However,
      the effects of many-particle correlation have been relatively unexplored in
      perovskite because of the difficultly of probing these states directly. Here, we
      use double quantum coherence spectroscopy to explore the formation and
      localization of multiexciton states in these materials. Between the most confined
      domains, we demonstrate the presence of an interwell, two-exciton excited state.
      This demonstrates that the four-body Coulomb interaction electronically couples
      neighboring wells despite weak electron/hole hybridization in these materials.
      Additionally, in contrast with inorganic semiconductor quantum wells, we
      demonstrate a rapid decrease in the dephasing time as wells become thicker,
      indicating that exciton delocalization is not limited by structural inhomogeneity
      in low-dimensional perovskite.

PMID- 28767259
TI  - Interfacial Modification of Perovskite Solar Cells Using an Ultrathin MAI Layer
      Leads to Enhanced Energy Level Alignment, Efficiencies, and Reproducibility.
AB  - For the first time, we intentionally deposit an ultrathin layer of excess
      methylammonium iodide (MAI) on top of a methylammonium lead iodide (MAPI)
      perovskite film. Using photoelectron spectroscopy, we investigate the role of
      excess MAI at the interface between perovskite and spiro-MeOTAD hole-transport
      layer in standard structure perovskite solar cells (PSCs). We found that
      interfacial, favorable, energy-level tuning of the MAPI film can be achieved by
      controlling the amount of excess MAI on top of the MAPI film. Our XPS results
      reveal that MAI dissociates at low thicknesses (<16 nm) when deposited on MAPbI3.
      It is not the MAI layer but the dissociated species that leads to the interfacial
      energy-level tuning. Optimized interface energetics were verified by solar cell
      device testing, leading to both an increase of 19% in average steady-state power
      conversion efficiency (PCE) and significantly improved reproducibility, which is
      represented by a much lower PCE standard deviation (from 15 +/- 2% to 17.2 +/-
      0.4%).

PMID- 28767260
TI  - [The Black Eagle pharmacy in Petrinja - first civil pharmacy on the territory of
      Banska krajina].
AB  - The Black Eagle pharmacy was founded in 1772 as a branch of the eponymous
      Karlovac pharmacy and was the oldest civil pharmacy on the territory of Banska
      krajina. Based on the archival sources, newspapers of the time, and the
      documentation preserved within the owner's family, its historical background and
      ownership chronology are presented in this paper. Special attention was dedicated
      to the Panac family, which led the pharmacy through four generations, from 1822
      until 1950. The results of our research resolved the dilemmas about the
      pharmacy's first location and also presented the information concerning the
      academic path of its owners, their work, as well as their wider socio-cultural
      influences on life in Petrinja. The interior of The Black Eagle pharmacy has not
      retained its original function nor has the inventory been preserved, although the
      building, in which it was located, has been preserved and is protected as a
      cultural monument. The pharmacy was nationalized in 1947, and moved to a new
      location towards the end of 1950s. Therefore, the reconstruction of its
      historiography contributes not only to our knowledge of the pharmacy development
      in Croatia, but also to the understanding of the development of the city through
      the emergence and existence of medical and healthcare institutions within the
      city.

PMID- 28767261
TI  - [Health maps of a historical population in nineteenth-century Friuli
      (Northeastern Italy)].
AB  - This paper aims at presenting some health maps of a historical population. The
      studies on the health status of past populations are usually focused on the
      causes of death. Our purpose is to present some descriptive analyses on non
      deadly diseases. The present work focuses on the province of Friuli (north
      eastern Italy) in the second half of the nineteenth century. The used sources are
      military call-up records. We collected about 300,000 records relative to military
      recruitment that took place between 1866 and 1909 (birth cohorts 1846-1890). Our
      main concern was the health status of the 20-year male population, and its
      association with environmental, socio economic and genetic factors. Generally
      speaking, we observe that the northern mountain area was the most advantaged,
      while young adults from the eastern and western parts of the province were the
      most disadvantaged. A lot of factors and causes contributed to determine the
      spatial distribution of specific diseases in Friuli, whilst others remain unknown
      because simple descriptive analyses are not sufficient to highlight them all. In
      particular, the distribution of the thyroidal hypertrophy was almost certainly
      due to the water quality, while the distribution of dental caries was probably
      related to genetic and dietary factors.

PMID- 28767262
TI  - Framing "our social disaster": narratives of disease and sexuality in Turkey's
      early republic.
AB  - For the early Turkish republic, resource shortages, illiteracy, and geography
      combined to hamper any achievement of the immediate and universal diffusion of
      state-authored lessons in public health throughout the country's populace. One of
      the first steps taken to overcome these obstacles involved the production and
      publication of a medical atlas. Ideally, this text would serve both to
      standardize care provided by the state's health professionals and to inform the
      entire population of their public health obligations and compel their compliance;
      longer lives, prosperity, and a stronger nation were the promised outcomes.
      However, utilizing public health education to institute this state-society
      contract also entailed framing diseases in particular ways. This was especially
      true with sexually-transmitted infections (STIs), and the narratives associated
      with STIs marginalized routinely specific subpopulations of the Turkish nation;
      women and girls, generally, and sex workers, in particular. Focusing on this
      primary text, this article engages critically with the atlas to document,
      analyze, and inform the nature of this promise and the types of medical and moral
      norms that it imposed and reinforced.

PMID- 28767263
TI  - Trepanation and enlarged parietal foramen on skulls from the Loyalty Islands
      (Melanesia).
AB  - The goal of this study is a comprehensive examination of openings discovered on
      two skulls in the collection of skeletal remains from the Loyalty Islands
      (Melanesia). The skull No. 1524 displayed an evidence of successful trepanation,
      and the skull No. 7985 revealed openings that were reminiscent of a trepanation,
      however, we are inclined to believe that in the latter case we are dealing with a
      rare genetic anomaly - enlarged parietal foramen.

PMID- 28767264
TI  - Human urine-based therapeutics in Spain from the early 20th century to the
      present: a historical literature overview and a present-day case study.
AB  - Human urine is currently the subject of biomedical investigations as a potential
      therapeutic resource and it continues to be used in remedies in different
      cultures and societies, including the Spanish culture. In this study we gather
      etnomedical knowledge about urotherapy and determine their associated symbolisms
      in Spain. A literature overview and a case study were carried out to compile
      urine-based remedies and as a direct analysis of symbolic systems. Urotherapy is
      widespread in Spanish folk medicine. Among the 204 collected remedies, those
      related to treatment of diseases or skin conditions predominate (63%). Remedies
      have been reported for the treatment of skin diseases such as eczema, chloasma,
      alopecia, etc. to treat or alleviate burns, chilblains, wounds or skin chapping,
      and as a treatment of venomous bites. Most of the collected remedies have an
      associated naturalist symbolism, based on local traditions and the transmission
      of empirical initial knowledge. The use of urine in Spain is a result of the
      interaction of two types of practice: a local and traditional urotherapy, rural
      and with a utilitarian purpose, and a technical urotherapy, limited to an urban
      environment and a naturopathic medicine.

PMID- 28767265
TI  - Professors, principals and textbooks from the Midwifery school in Zadar.
AB  - Midwifery in Dalmatia was highly undeveloped at the beginning of the XIX century.
      The health report from 1813 suggested that there were only 48 midwives in the
      whole province, and none of them with a degree from the midwifery school. After
      abolishing the Central Schools ("Ecoles Centrales"), which were founded at the
      time of French reign, and which had the university range, the professors who
      stayed in Zadar continued their work and teaching in the Midwifery School, which
      was founded in 1820 according to the decision made by Emperor Franz I, and
      started working in 1821. Since the school was working continuously for the whole
      century, a lot of professors and principals passed through. Protomedicus of
      Dalmatia officially performed the duty of principals of the Midwifery School.
      Their life and work biographies were gathered in this paper. Although the
      newcomers were mostly illiterate, very contemporary and valuable textbooks were
      used at that time. The professors of this school wrote some of these textbooks.
      This paper analyses those textbooks from the current medical science and praxis
      point of view, which points out to its significance and contribution of its
      authors to the reputation that the School enjoyed at that time.

PMID- 28767266
TI  - Paul Langerhans: a prilgrim "traveling" from functional histology to marine
      biology.
AB  - The nineteenth century was the time of a real revolution in science and medicine.
      A lot of seminal discoveries in medicine and biology were done in this time, and
      many of them were coincident with the introduction of the compound microscope by
      Hermann van Deijl and the standard histological technique by Paul Ehrlich. The
      main tissue types and individual cells were characterized and originally
      classified more than hundred years ago, although less attention was paid to their
      basic functions. This was mainly due to the modality of tissue specimen
      processing that allowed particularly detailed descriptive studies. Even so, we
      can notice some attempts to correlate the structure with the function. The German
      scientist Paul Langerhans, well-known for the discovery of Langerhans islets of
      the pancreas and Langerhans cells from the epidermis, tried to change the
      conventional fate of morphological studies introducing in his works functional
      hypothesis based on traditional microscopic observations even from the beginning
      of his scientific career. Paul Langerhans was a complex personality of the second
      half of the nineteenth century, not only in medicine, but also in other fields of
      biology. In the present review, presented is the life and research activity of
      Paul Langerhans, not only because of the importance of his discoveries, but also
      for perspectives that were opened by these findings in unexpected fields of
      medicine and biology.

PMID- 28767267
TI  - [Approach to illness and death of Vadinienses in roman Hispania (I-IV
      centuries)].
AB  - The Vadinienses were a Cantabrian people who lived between the first and fourth
      centuries in the north of the Iberian Peninsula, northeast of the present
      province of Leon and the corresponding part of the current territory of Asturias.
      In this paper we study the possible causes of illness and death of the
      Vadinienses represented in their gravestones. The analysis of Vadinienses
      epitaphs shows that two-thirds of the deaths occurred in people between the ages
      of 20-30, a finding that is not interpreted as representative of the usual age of
      death at that time. The most likely causes of death are infections and violent
      deaths in sports competitions or work accidents. Analyzing females independently,
      almost half of the deceased were under the age of 20, being the main
      possibilities the deaths related to pregnancy and childbirth at very early ages.

PMID- 28767268
TI  - Can the WIND Definition Classify All Invasively Ventilated Patients?

PMID- 28767269
TI  - Reply to Wang et al.: Can the WIND Definition Classify All Invasively Ventilated
      Patients?

PMID- 28767270
TI  - Fifty Years of Research in ARDS. Long-Term Follow-up after Acute Respiratory
      Distress Syndrome. Insights for Managing Medical Complexity after Critical
      Illness.
AB  - Critical illness is not a discrete disease state or syndrome. It is the
      culmination of a multiplicity of heterogeneous disease states and their varied
      health trajectories leading to extreme illness that requires advanced life
      support in a distinct geographic location in the hospital. It is a marker of
      newly acquired or worsened medical complexity and multimorbidities. Fifty years
      ago, distinguished critical care colleagues identified a syndrome of severe lung
      injury that united a group of patients with disparate admitting diagnoses. Acute
      respiratory distress syndrome continues to represent an important, incremental
      insult and risk modifier of acute and longer-term outcome, but it does not solely
      define our patients or their outcomes in isolation. Over the next 50 years, our
      research and clinical agenda needs to sharpen our lens on the fundamental
      importance of our patients' pre-critical illness health status, their intrinsic
      susceptibilities to tissue injury, and their innate and varied resiliencies. We
      need to take responsibility for the contribution that we make to morbidity
      through our practice in the intensive care unit each day. Engagement in frank and
      transparent communication with our patients and their caregivers about the very
      real and morbid consequences of being this sick is essential. We must enforce
      explicit consent about the morbidity of innovative, experimental, or high-risk
      medical and surgical procedures and ensure that our ongoing level of treatment
      aligns with patients' and caregivers' goals and values. Interprofessional and
      multidisciplinary collaboration is crucial to modify existing complex care
      pathways for our patients and their families to foster optimal rehabilitation and
      reintegration into the workplace and community.

PMID- 28767271
TI  - Effects of Transcutaneous Electrical Acupoint Stimulation on Motor Functions and
      Self-Care Ability in Children with Cerebral Palsy.
AB  - OBJECTIVES: To observe the effects of transcutaneous electrical acupoint
      stimulation (TEAS) in improving motor functions and self-care abilities in
      children with cerebral palsy in their early childhood. DESIGN: A preliminary,
      prospective, cohort study. SETTINGS/LOCATION: Multicenter. SUBJECTS: Children
      aged 2-6 years old. INTERVENTIONS: Twenty-three children were included in the
      study and randomly assigned to a control group ([CG] N = 11) or a therapeutic
      group ([TG] N = 12). In the TG, children were treated with TEAS (Shousanli [LI10]
      and Waiguan [SJ5]) plus the exercise therapy, while in the control group, they
      were treated with sham TEAS plus exercise therapy. Therapies were performed five
      days per week for eight weeks. OUTCOME MEASURES: The Gross Motor Function Measure
      (GMFM) and the Functional Independent Measurement for children (WeeFIM) were used
      to evaluate motor functions and self-care abilities before and after the
      therapies. RESULTS: Greater improvements were observed in the TG concerning all
      the measurements, although without statistical differences. The increments of the
      GMFM score and the WeeFIM motor, self-care and total scores were 36.08 +/- 18.34
      (26%), 16.17 +/- 8.21 (33%), 7.67 +/- 3.42 (40%) and 20.33 +/- 10.08 (28%) in the
      TG, while 22.73 +/- 16.54 (17%), 9.09 +/- 9.43 (19%), 5.64 +/- 6.73 (29%) and
      12.82 +/- 11.77 (18%) in the CG, respectively. No statistically significant
      correlations were shown between functional improvements and the demographics in
      the TG or the CG. The GMFM improvement was not statistically correlated with the
      improvements of the WeeFIM motor, self-care or total scores. However, the WeeFIM
      motor, self-care and total score were significantly positively correlated with
      one another in both groups (P < 0.01). No adverse effect was recorded during the
      study. CONCLUSION: TEAS may be effective in improving motor functions and self
      care abilities in children with cerebral palsy, in addition to conventional
      exercise therapy. Larger samples are required to confirm the efficacies.

PMID- 28767272
TI  - User Statistics for an Online Health Game Targeted at Children.
AB  - OBJECTIVE: Given that many households in western countries nowadays have home
      access to the Internet, developing health-promoting online interventions has the
      potential to reach large audiences. Studies assessing usage data of online health
      interventions are important and relevant but, as of yet, scarce. The present
      study reviewed usage data from Monkey Do, an existing online health game
      developed specifically for children from 4 to 8 years old. In addition, the
      effect of advertising on usage was examined. MATERIALS AND METHODS: In an
      observational study, a web-based analysis program was used to examine usage data
      of all visits to the online health game for the first 31 months following the
      launch. We reported descriptives for usage data. We analyzed the relationship
      between advertising and usage with a Mann-Whitney U test, and used a Pearson's
      chi-square test to investigate the association between advertising and the number
      of first-time visitors. RESULTS: In the period of data analysis, there were
      224,859 sessions. Around 34% of the visitors played the game more than once.
      Compared with first-time visitors, the average session time of returning visitors
      was doubled. The game was most frequently accessed via search engine query, on a
      desktop computer (compared to mobile devices). Advertising was found to be
      positively related to the number of sessions and the number of first-time
      visitors. CONCLUSIONS: Placing a game online can reach a large audience, but it
      is important to also consider how to stimulate retention. Furthermore, repeated
      advertisement for an online game appears to be necessary to maintain visitors
      over time.

PMID- 28767273
TI  - Advances in Subcutaneous Glucose Sensing.

PMID- 28767274
TI  - Pricing Externalities to Balance Public Risks and Benefits of Research.
AB  - How should scientific funders evaluate research with public health risks? Some
      risky work is valuable, but accepting too much risk may be ethically neglectful.
      Recent controversy over H5N1 influenza experiments has highlighted the difficulty
      of this problem. Advocates of the research claim the work is needed to understand
      pandemics, while opponents claim that accidents or misuse could release the very
      pandemic the work is meant to prevent. In an attempt to resolve the debate, the
      US government sponsored an independent evaluation that successfully produced a
      quantitative estimate of the risks involved, but only a qualitative estimate of
      the benefits. Given the difficulties of this "apples-to-oranges" risk-benefit
      analysis, what is the best way forward? Here we outline a general approach for
      balancing risks and benefits of research with public risks. Instead of directly
      comparing risks and benefits, our approach requires only an estimate of risk,
      which is then translated into a financial price. This estimate can be obtained
      either through a centrally commissioned risk assessment or by mandating liability
      insurance, which allows private markets to estimate the financial burden of risky
      research. The resulting price can then be included in the cost of the research,
      enabling funders to evaluate grants as usual-comparing the scientific merits of a
      project against its full cost to society. This approach has the advantage of
      aligning incentives by assigning costs to those responsible for risks. It also
      keeps scientific funding decisions in the hands of scientists, while involving
      the public on questions of values and risk experts on risk evaluation.

PMID- 28767275
TI  - Recovery high schools: Effect of schools supporting recovery from substance use
      disorders.
AB  - BACKGROUND: Recovery high schools (RHSs) provide post-treatment education and
      recovery support for young people with substance use disorders (SUDs). This is
      the first quasi-experimental outcome study to determine RHS effectiveness
      relative to students in non-RHSs. OBJECTIVES: To examine effects of RHS
      attendance on academic and substance use outcomes among adolescents treated for
      SUDs 6 months after recruitment to the study. METHODS: A quasi-experimental
      design comparing outcomes for adolescents with treated SUDs who attended RHSs for
      at least 28 days versus a propensity-score balanced sample of students with
      treated SUDs who did not attend RHSs. The sample included 194 adolescents (134 in
      RHSs, 60 in non-RHSs) enrolled in Minnesota, Wisconsin, or Texas schools (M age =
      16; 86% White; 49% female). Multilevel linear regression models were used to
      examine the effect of RHS attendance on students' outcomes, after adjusting for a
      range of potential confounders. RESULTS: Adolescents attending RHSs were
      significantly more likely than non-RHS students to report complete abstinence
      from alcohol, marijuana, and other drugs at the 6-month follow-up (OR = 4.36, p =
      .026), significantly lower levels of marijuana use (d = -0.51, p = .034) and less
      absenteeism from school (d = -0.56, p = .028). CONCLUSION: These results indicate
      that RHSs have significantly beneficial effects on substance use and school
      absenteeism after 6 months for adolescents treated for SUDs.

PMID- 28767277
TI  - Using Zebrafish to Test the Genetic Basis of Human Craniofacial Diseases.
AB  - Genome-wide association studies (GWASs) opened an innovative and productive
      avenue to investigate the molecular basis of human craniofacial disease. However,
      GWASs identify candidate genes only; they do not prove that any particular one is
      the functional villain underlying disease or just an unlucky genomic bystander.
      Genetic manipulation of animal models is the best approach to reveal which
      genetic loci identified from human GWASs are functionally related to specific
      diseases. The purpose of this review is to discuss the potential of zebrafish to
      resolve which candidate genetic loci are mechanistic drivers of craniofacial
      diseases. Many anatomic, embryonic, and genetic features of craniofacial
      development are conserved among zebrafish and mammals, making zebrafish a good
      model of craniofacial diseases. Also, the ability to manipulate gene function in
      zebrafish was greatly expanded over the past 20 y, enabling systems such as
      Gateway Tol2 and CRISPR-Cas9 to test gain- and loss-of-function alleles
      identified from human GWASs in coding and noncoding regions of DNA. With the
      optimization of genetic editing methods, large numbers of candidate genes can be
      efficiently interrogated. Finding the functional villains that underlie diseases
      will permit new treatments and prevention strategies and will increase
      understanding of how gene pathways operate during normal development.

PMID- 28767278
TI  - The History and Current Status of the Academy of Breastfeeding Medicine's
      Regional Network Coordinators.

PMID- 28767276
TI  - Closed-Loop Control Without Meal Announcement in Type 1 Diabetes.
AB  - OBJECTIVE: A fully closed-loop insulin-only system was developed to provide
      glucose control in patients with type 1 diabetes without requiring announcement
      of meals or activity. Our goal was to assess initial safety and efficacy of this
      system. RESEARCH DESIGN AND METHODS: The multiple model probabilistic controller
      (MMPPC) anticipates meals when the patient is awake. The controller used the
      subject's basal rates and total daily insulin dose for initialization. The system
      was tested at two sites on 10 patients in a 30-h inpatient study, followed by 15
      subjects at three sites in a 54-h supervised hotel study, where the controller
      was challenged by exercise and unannounced meals. The system was implemented on
      the UVA DiAs system using a Roche Spirit Combo Insulin Pump and a Dexcom G4
      Continuous Glucose Monitor. RESULTS: The mean overall (24-h basis) and nighttime
      (11 PM-7 AM) continuous glucose monitoring (CGM) values were 142 and 125 mg/dL
      during the inpatient study. The hotel study used a different daytime tuning and
      manual announcement, instead of automatic detection, of sleep and wake periods.
      This resulted in mean overall (24-h basis) and nighttime CGM values of 152 and
      139 mg/dL for the hotel study and there was also a reduction in hypoglycemia
      events from 1.6 to 0.91 events/patient/day. CONCLUSIONS: The MMPPC system
      achieved a mean glucose that would be particularly helpful for people with an
      elevated A1c as a result of frequent missed meal boluses. Current full closed
      loop has a higher risk for hypoglycemia when compared with algorithms using meal
      announcement.

PMID- 28767279
TI  - The Inappropriate Use of Risk-Benefit Analysis in the Risk Assessment of
      Experimental Trauma-Focused Research.
AB  - A large body of research has explored the impact of questioning participants
      about traumatic experiences. To determine the level of risk, these studies have
      relied, to various degrees, upon a risk-benefit calculus, whereby risks are
      weighed against the benefits that an individual can receive from participating.
      In the case of trauma-focused studies this approach is erroneous. The procedures
      involved in trauma-focused studies do not meet the criteria to be considered
      therapeutic, and the benefits associated with these procedures do not carry the
      moral weight to offset risk. Applying the risk-benefit calculus to non
      therapeutic procedures inevitably leads to inaccurate risk assessments and
      ethically problematic claims, examples of which can be found throughout traumatic
      stress literature. This article outlines how the standard approach to risk
      assessment in trauma-focused studies is fallacious, and presents an established
      alternative model that researchers can use to accurately assess the risks of
      asking participants about their traumatic experiences.

PMID- 28767280
TI  - Yoga practice is associated with superior motor imagery performance.
AB  - Yoga is an activity that aims to integrate physical, mental and spiritual
      elements and is an increasingly popular approach to enhancing physical fitness.
      The integration of imagery within yoga practice is considered an important
      component and may be critical in contributing to the benefits of yoga that have
      been reported. In this study, we tested whether individuals who practice yoga
      demonstrate superior performance on an objective measure of implicit motor
      imagery. Thirty-six participants (18 yoga, 18 nonyoga) matched for age, sex and
      handedness, undertook the hand laterality recognition task; an objective measure
      of implicit motor imagery performance. Accuracy and response times were gathered
      and analysed to determine any group differences as well as any differences
      relating to the typical hallmarks of imagery (i.e. dominance and awkwardness
      effects) on the task. Response Times (RTs) in the yoga group were significantly
      faster than controls (p < 0.05) and there was also a trend towards greater
      accuracy for the Yoga group (p = 0.073). Dominance effects (faster responses to
      images corresponding with the dominant limb) and Awkwardness effects (faster
      responses to images corresponding with natural compared with awkward postures)
      were evident across groups, supporting the participants' use of motor imagery in
      undertaking the task. Additionally, a Group * Awkwardness interaction (p < 0.05)
      revealed that the enhanced imagery performance for the yoga group was most
      pronounced for awkward postures. This is the first study to show that yoga
      practice is associated with superior motor imagery performance; an association
      that may be important in explaining the established rehabilitative value of yoga
      for chronic pain.

PMID- 28767281
TI  - The Impact of Prenatal Yoga on Exercise Attitudes and Behavior: Teachable moments
      from a Randomized Controlled Trial.
AB  - OBJECTIVE: Pregnancy serves as an opportune time for "teachable moments" to
      elicit positive behavior change. We evaluated change in exercise perception,
      behavior and gestational weight gain in participants engaged in a one-hour
      educational experience. METHODS: Women between 28 0/7 to 36 6/7 weeks with no
      prior yoga experience carrying a non-anomalous singleton fetus participated in a
      randomized controlled trial on prenatal yoga. The yoga group engaged in a one
      hour yoga class; the attention control educational group, in a one-hour
      presentation on exercise, nutrition and obesity in pregnancy. Maternal perception
      of yoga, exercise effects and current health status was conducted before and
      after the intervention. Gestational weight gain (GWG) and body mass index (BMI)
      were assessed. A postpartum survey was performed to determine self-reported
      behavioral changes during and after pregnancy. RESULTS: Over 6 months, 52 women
      were randomized and 46 (88%) completed the study. Women reported a more positive
      attitude towards exercise and yoga after the yoga intervention. Total GWG was
      similar (yoga 32.9 versus education 32.8 pounds, p = 0.98). Stratified by pre
      pregnancy BMI, 13% gained within and 61% gained above the Institute of Medicine
      guidelines in each group. Of 29 inactive women prior to the intervention, 60% of
      the yoga group and 75% of the education group began prenatal exercises after the
      intervention and 50% of each group continued to exercise after delivery. There
      were no significant differences between groups. CONCLUSION: A one-time, one-hour
      intervention teaching a new exercise or educating women during pregnancy can
      positively impact pregnancy behaviors and perception with the potential to
      improve maternal and neonatal outcomes.

PMID- 28767282
TI  - Supplement A, July 2017.

PMID- 28767283
TI  - Precursor Lesions of Urologic Malignancies.
AB  - CONTEXT: - Precursor lesions of urologic malignancies are established
      histopathologic entities, which are important not only to recognize for clinical
      purposes, but also to further investigate at the molecular level in order to gain
      a better understanding of the pathogenesis of these malignancies. OBJECTIVE: - To
      provide a brief overview of precursor lesions to the most common malignancies
      that develop within the genitourinary tract with a focus on their clinical
      implications, histologic features, and molecular characteristics. DATA SOURCES: -
      Literature review from PubMed, urologic pathology textbooks, and the 4th edition
      of the World Health Organization Classification of Tumours of the Urinary System
      and Male Genital Organs. All photomicrographs were taken from cases seen at Weill
      Cornell Medicine or from the authors' personal slide collections. CONCLUSIONS: -
      The clinical importance and histologic criteria are well established for the
      known precursor lesions of the most common malignancies throughout the
      genitourinary tract, but further investigation is warranted at the molecular
      level to better understand the pathogenesis of these lesions. Such investigation
      may lead to better risk stratification of patients and potentially novel
      treatments.

PMID- 28767284
TI  - Commutability of Reference Materials for alpha-Fetoprotein in Human Serum.
AB  - CONTEXT: - Reliable quantification of alpha-fetoprotein (AFP) is critical for
      clinical diagnosis. Accuracy in AFP analysis relies on traceability to reference
      materials with confirmed commutability. OBJECTIVE: - To assess the commutability
      of the reference materials for AFP. We screened for appropriate reference
      materials for the calibration of clinical AFP analysis and for application in an
      external quality assessment scheme. The feasibility of using water to dilute a
      reference material from the World Health Organization was also evaluated. DESIGN:
      - Patient serum samples with various levels of AFP were randomly interspersed
      among AFP reference materials from the World Health Organization, the Beijing
      Center for Clinical Laboratories, and Beijing Controls and Standards
      Biotechnology and quality controls from Bio-Rad. The samples were analyzed on 5
      different platforms to assess the comparability of the results and commutability
      of the reference materials. RESULTS: - Significant variations in AFP measurement
      were observed among the 5 instrument platforms. The Beijing Center for Clinical
      Laboratories and Beijing Controls and Standards Biotechnology reference materials
      were commutable across all the instrument platforms. The World Health
      Organization AFP 72/225 reference material diluted with distilled water was also
      commutable at high concentrations. The Bio-Rad quality control materials for AFP
      were commutable among 4 out of 5 instrument platforms. CONCLUSIONS: - Our results
      suggested that the Beijing Center for Clinical Laboratories and Beijing Controls
      and Standards Biotechnology materials were commutable across all 5 instrument
      platforms, whereas the Bio-Rad quality controls were limited by the concentration
      of AFP and the instrument platforms used. Caution needs to be taken in using
      water to dilute the World Health Organization 72/225 reference material because
      its commutability is limited to high concentrations.

PMID- 28767285
TI  - Listeria monocytogenes in Food-Processing Facilities, Food Contamination, and
      Human Listeriosis: The Brazilian Scenario.
AB  - Listeria monocytogenes is a foodborne pathogen that contaminates food-processing
      environments and persists within biofilms on equipment, utensils, floors, and
      drains, ultimately reaching final products by cross-contamination. This pathogen
      grows even under high salt conditions or refrigeration temperatures, remaining
      viable in various food products until the end of their shelf life. While the
      estimated incidence of listeriosis is lower than other enteric illnesses,
      infections caused by L. monocytogenes are more likely to lead to hospitalizations
      and fatalities. Despite the description of L. monocytogenes occurrence in
      Brazilian food-processing facilities and foods, there is a lack of consistent
      data regarding listeriosis cases and outbreaks directly associated with food
      consumption. Listeriosis requires rapid treatment with antibiotics and most drugs
      suitable for Gram-positive bacteria are effective against L. monocytogenes. Only
      a minority of clinical antibiotic-resistant L. monocytogenes strains have been
      described so far; whereas many strains recovered from food-processing facilities
      and foods exhibited resistance to antimicrobials not suitable against
      listeriosis. L. monocytogenes control in food industries is a challenge,
      demanding proper cleaning and application of sanitization procedures to eliminate
      this foodborne pathogen from the food-processing environment and ensure food
      safety. This review focuses on presenting the L. monocytogenes distribution in
      food-processing environment, food contamination, and control in the food
      industry, as well as the consequences of listeriosis to human health, providing a
      comparison of the current Brazilian situation with the international scenario.

PMID- 28767286
TI  - Defining the Synthetic Biology Supply Chain.
AB  - Several recent articles have described risks posed by synthetic biology and
      spurred vigorous discussion in the scientific, commercial, and government
      communities about how to best detect, prevent, regulate, and respond to these
      risks. The Pacific Northwest National Laboratory's (PNNL) deep experience working
      with dual-use technologies for the nuclear industry has shown that analysis of
      supply chains can reveal security vulnerabilities and ways to mitigate security
      risk without hindering beneficial research and commerce. In this article, a team
      of experts in synthetic biology, data analytics, and national security describe
      the overall supply chain surrounding synthetic biology to illustrate new insights
      about the effectiveness of current regulations, the possible need for different
      screening approaches, and new technical solutions that could help identify or
      mitigate risks in the synthetic biology supply chain.

PMID- 28767287
TI  - Feeding Practices and Infant Growth: Quantifying the Effects of Breastfeeding
      Termination and Complementary Food Introduction on BMI z-Score Growth Velocity
      through Growth Curve Models.
AB  - BACKGROUND: Infant feeding practices are a focus of early obesity prevention. We
      tested whether infant growth velocity increased after breastfeeding termination
      and complementary food introduction. METHODS: Our secondary analysis included a
      sample of 547 mother-infant dyads from a longitudinal randomized controlled trial
      conducted in Michigan and Colorado. Infant anthropometrics at birth, baseline,
      and 6- and 12-month follow-up were standardized to BMI-for-age z-score (ZBMI)
      according to World Health Organization (WHO) growth charts. We used growth curve
      models with time-varying predictors to quantify effects of breastfeeding
      termination and timing of complementary food introduction on growth velocity.
      RESULTS: Median breastfeeding duration was 2.0 months [confidence interval (CI) =
      2.0-2.5]; median introduction of complementary foods occurred at 3.0 months (CI =
      2.8-3.2). Breastfed infants not yet introduced to complementary foods had an
      average ZBMI growth velocity of 0.050 (CI = -0.013 to 0.113) z-score units per
      month [zpm], not significantly faster than WHO growth trajectory (p = 0.118)
      defined as 0 zpm. Breastfeeding termination had negligible effect on ZBMI growth
      velocity (gamma11 = 0.001, CI = -0.027 to 0.030, p = 0.927). Introduction of
      complementary foods increased ZBMI growth velocity relative to an average child
      in the sample, but not significantly (gamma12 = 0.033, CI = -0.034 to 0.100, p =
      0.334). Growth velocities for infants receiving complementary foods both before
      and after breastfeeding termination were significantly faster than the WHO growth
      trajectory (0.083 zpm, CI = 0.052-0.114, and 0.084 zpm, CI = 0.064-0.105,
      respectively, p's < 0.001). CONCLUSIONS: Average postcomplementary food
      introduction growth velocity was significantly higher than WHO growth trajectory,
      but did not differ from the sample's initial average trajectory. Growth curve
      models can accurately estimate effects of feeding practices on infant growth to
      direct obesity prevention efforts.

PMID- 28767288
TI  - Arsenic Trioxide Consolidation Allows Anthracycline Dose Reduction for Pediatric
      Patients With Acute Promyelocytic Leukemia: Report From the Children's Oncology
      Group Phase III Historically Controlled Trial AAML0631.
AB  - Purpose The Children's Oncology Group AAML0631 trial for newly diagnosed
      pediatric acute promyelocytic leukemia (APL) was a phase III historically
      controlled trial to determine the survival of patients receiving arsenic trioxide
      (ATO) consolidation and reduced doses of anthracyclines. Patients and Methods
      Patients age 2 to 21 years with de novo APL confirmed by PML-RARalpha polymerase
      chain reaction were stratified as standard risk (SR) or high risk (HR) on the
      basis of diagnostic WBC count. All patients received all-trans retinoic acid
      (ATRA) during induction, each consolidation course, and maintenance. All patients
      received two cycles of ATO therapy during consolidation 1, an additional two (SR)
      or three (HR) consolidation courses that included high-dose cytarabine and
      anthracycline, and maintenance therapy comprising ATRA, oral methotrexate, and
      mercaptopurine. Results One hundred one patients (66 SR and 35 HR) were evaluable
      for outcome. The 3-year overall survival was 94%, and event-free survival (EFS)
      was 91%. For SR and HR patients with APL, the overall survival was 98% versus 86%
      ( P = .003), and EFS was 95% versus 83% ( P = .03), respectively. The EFS for SR
      patients in AAML0631 was noninferior to that of patients in the AIDA 0493
      historical control, which used a significantly higher anthracycline dose and did
      not include ATO consolidation. Relapse risk for patients in AAML0631 from end
      consolidation 1 (after ATO treatment) was only 4% at 3 years and did not differ
      significantly between SR and HR patients. Conclusion ATO consolidation cycles
      were well tolerated in pediatric patients with APL and allowed significant
      reduction in cumulative anthracycline doses while maintaining excellent survival
      and a low relapse risk for both SR and HR patients with APL.

PMID- 28767290
TI  - GROW: Green Organic Vegetable Gardens to Promote Older Adult Wellness: a
      Feasibility Study.
AB  - Protecting older adult's cognitive health is a public health priority. Wellness
      behaviors within 6 domains have demonstrated effectiveness in protecting older
      adult's cognitive abilities. Interventions targeted to low-income older adults
      are needed because these populations experience greater social and physical
      health disparities compared to adults in higher socioeconomic statuses. This
      study examined the feasibility of engaging independent, community-dwelling older
      adults living in low-income senior housing in cultivating raised-bed gardens and
      reviewed the improvements in cognition and nutrition. Ten participants received
      ergonomic garden tools, seeds, waist-height garden beds, and weekly garden
      education. Participants planted vegetables of their choosing and tended to their
      garden beds for 17 weeks. Cognition and nutrition outcomes were measured before
      and after the intervention. Adults successfully engaged in the intervention
      throughout the duration and experienced improvement in cognitive and nutrition
      outcomes.

PMID- 28767291
TI  - Improving Asthma Control through Asthma Action Plans: A Quality Improvement
      Project at a Midwest Community Clinic.
AB  - This urban community clinic had poor asthma outcomes compared to the state of
      Minnesota. The standard of care supports an annual Asthma Action Plan (AAP).
      However, the majority of patients at this clinic had not received one. This
      quality improvement project aimed to improve asthma control, measured by an
      asthma control test of at least 20, through AAP implementation supported by all
      team members. The clinic's interdisciplinary champion group implemented workflow
      changes via practice facilitation and Plan-Do-Study-Act cycles. Asthma control
      rates increased from 23% to 58% in adults and 45% to 63% in children over one
      year, a statistically significant change.

PMID- 28767289
TI  - Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic
      Adenocarcinoma.
AB  - Purpose Deleterious germline mutations contribute to pancreatic cancer
      susceptibility and are well documented in families in which multiple members have
      had pancreatic cancer. Methods To define the prevalence of these germline
      mutations in patients with apparently sporadic pancreatic cancer, we sequenced 32
      genes, including known pancreatic cancer susceptibility genes, in DNA prepared
      from normal tissue obtained from 854 patients with pancreatic ductal
      adenocarcinoma, 288 patients with other pancreatic and periampullary neoplasms,
      and 51 patients with non-neoplastic diseases who underwent pancreatic resection
      at Johns Hopkins Hospital between 2000 and 2015. Results Thirty-three (3.9%; 95%
      CI, 3.0% to 5.8%) of 854 patients with pancreatic cancer had a deleterious
      germline mutation, 31 (3.5%) of which affected known familial pancreatic cancer
      susceptibility genes: BRCA2 (12 patients), ATM (10 patients), BRCA1 (3 patients),
      PALB2 (2 patients), MLH1 (2 patients), CDKN2A (1 patient), and TP53 (1 patient).
      Patients with these germline mutations were younger than those without (mean +/-
      SD, 60.8 +/- 10.6 v 65.1 +/- 10.5 years; P = .03). Deleterious germline mutations
      were also found in BUB1B (1) and BUB3 (1). Only three of these 33 patients had
      reported a family history of pancreatic cancer, and most did not have a cancer
      family history to suggest an inherited cancer syndrome. Five (1.7%) of 288
      patients with other periampullary neoplasms also had a deleterious germline
      mutation. Conclusion Germline mutations in pancreatic cancer susceptibility genes
      are commonly identified in patients with pancreatic cancer without a significant
      family history of cancer. These deleterious pancreatic cancer susceptibility gene
      mutations, some of which are therapeutically targetable, will be missed if
      current family history guidelines are the main criteria used to determine the
      appropriateness of gene testing.

PMID- 28767292
TI  - US Healthcare Experiences of Hispanic Patients with Diabetes and Family Members:
      A Qualitative Analysis.
AB  - Hispanics in the United States experience significant health disparities. Using
      focus groups conducted in Spanish, we explored the perspectives of 172 Hispanic
      adults regarding their healthcare experiences. Many participants were women
      (64.5%) and primarily from Mexico (80%). Four major qualitative themes emerged:
      (a) provide us with information, (b) want attentive and respectful relationships,
      (c) want better care, and (d) perceived discrimination. Suboptimal patient
      provider interactions were described. Research is needed to explore interventions
      that address these issues. Incorporating person-centered care principles and
      practices such as clear and understandable communication, culturally competent
      care, and customer service skills may benefit provider interactions with
      Hispanics.

PMID- 28767294
TI  - Development and Preliminary Testing of a Smartphone-Based Injury-Prevention
      Application (S-IPA) for Teachers at Child-Care Centers in South Korea.
AB  - The purpose of this study was to develop a smartphone-based injury-prevention
      application (S-IPA) for teachers working in child-care centers, and to test the
      satisfaction level of the users of the application (app). Through a literature
      review and needs assessment, an app compatible with the Apple iPhone operating
      system was developed. The app was verified and the mean total satisfaction with 7
      features of the app was 7.76 (+/- 1.13) on a score of 1-10. The result of the S
      IPA survey showed a positive response, indicating a high potential for use as a
      teacher's educational guide, which would provide an effective information
      delivery system for the prevention of possible injuries at child-care centers.

PMID- 28767295
TI  - Our Children, Our Hope: Voices of African American Mothers Living with HIV and
      Rearing Uninfected Children.
AB  - Parenting school-aged children while living with HIV has been associated with
      significant consequences for African American mothers. This article presents and
      discusses the results of a qualitative study that examined the parenting
      experiences of HIV-infected African American mothers rearing young children. A
      sample of 8 inner-city, African American mothers of uninfected preschool-aged
      children were interviewed individually. Interview guide questions explored day-to
      day childcare activities from the mothers' perspective. Five themes emerged: role
      of mothering, doing it all, less time for self, fear, and hope. Findings can be
      used to guide the development of programs to support HIV-infected mothers rearing
      young children.

PMID- 28767296
TI  - Advance Care Planning Discussions with Adolescent and Young Adult Cancer Patients
      Admitted to a Community Palliative Care Service: A Retrospective Case-Note Audit.
AB  - PURPOSE: Adolescents and young adults (AYA) with cancer are a cohort requiring
      specialized healthcare models to address unique cognitive and physical
      challenges. Advance care planning (ACP) discussions likely warrant age
      appropriate adaptation, yet, there is little Australian research data available
      to inform best practice for this group. The goal of this work is to inform future
      models of ACP discussions for AYA. METHODS: Retrospective medical record audit of
      AYA patients and an adult comparison group, diagnosed with a malignancy and
      referred to a community hospice service, in Western Australia, in the period
      between January 1, 2012 and December 1, 2015. Information was collected regarding
      end-of-life care discussions, documentation of agreed plan of care, and care
      received. RESULTS: Twenty-seven AYA and 37 adult medical records were reviewed.
      Eighteen (66.7%) AYA patients died at home, compared with 19 (51.4%) adults (p =
      0.028). Desire to pursue all available oncological therapies, including clinical
      trials, was documented for 14 (51.9%) AYA patients compared with 9 (24.3%) of the
      adult group (p = 0.02). Eleven AYA patients (40.7%) received chemotherapy during
      the last month of life compared with two (5.4%) adults (p = 0.001). CONCLUSIONS:
      The results indicate that end-of-life care preferences for this unique cohort may
      differ from those of the adult population and need to be captured and understood.
      An ACP document incorporating a discussion regarding goals of care, preferred
      location of care, preference for place of death, and consent to future
      intervention, including cardiopulmonary resuscitation and prompts for review,
      could assist in pursuing this objective.

PMID- 28767297
TI  - Dentition Patterns in Different Unilateral Cleft Lip Subphenotypes.
AB  - Oral clefts play an essential role in disturbed odontogenesis of the deciduous
      and permanent dentition, yet little is known about this relationship. We
      investigated, within the categories cleft lip with or without alveolus (CL +/- A)
      and cleft lip, alveolus and palate (CLAP), whether different CL subphenotypes
      based on morphological severity of the cleft show different dentition patterns
      and whether a more detailed subdivision of the incomplete CL has clinical
      relevance. In this retrospective study, 345 children with nonsyndromic unilateral
      CL +/- A and CLAP from the Dutch Association for Cleft Palate and Craniofacial
      Anomalies (NVSCA) registry were included to assess the association between the CL
      subphenotypes and lateral incisor patterns. Five different deciduous and
      permanent patterns of the lateral incisor were distinguished: located in normal
      position (pattern z/Z), in the anterior segment (pattern x/X) or in the posterior
      segment of the cleft (pattern y/Y), one in each segment of the cleft (pattern
      xy/XY), and agenesis of the lateral incisor (pattern ab/AB). Analyses were
      performed by using multinomial logistic regression models. Children born with a
      vermillion notch or a one-third to two-thirds CL were most likely to have a
      deciduous pattern x and a permanent pattern X, while children born with a two
      thirds to subtotal CL were most likely to have deciduous pattern xy and a
      permanent pattern X compared to children with a complete CL that predominantly
      had deciduous pattern y and a permanent pattern AB. Based on the relationship of
      the CL morphology with the deciduous dentition, subdivision of the CL morphology
      into vermillion notch to two-thirds CL, two-thirds to subtotal CL, and complete
      CL appears to be an optimal subdivision. Our results indicate that a more
      detailed subdivision of the CL has clinical relevance and that critical factors
      in the pathogenesis of the CL are also critical for the odontogenesis.

PMID- 28767298
TI  - Consenting to sexual activity.
AB  - Engaging in sexual activity is an essential Human Right protected under article
      12 of the European Convention on Human Rights ( Council of Europe, 1950 ) and
      should be free from state interference. District nurses, however, often express
      concern over the possibility that adults with acquired brain injury or a learning
      disability cannot give a real consent to participate in sexual activity and so
      should be prevented from doing so. In this article Richard Griffith reviews the
      case law in relation to the capacity to consent to sexual activity.

PMID- 28767299
TI  - The Mental Capacity Act: 'Best interests'-a review of the literature.
AB  - The Mental Capacity Act (MCA) is statutory legislation introduced in 2007 in
      order to provide a consistent, robust framework with the aim to protect and
      empower people to make decisions themselves. However, an assessment as per the
      MCA may demonstrate that a person is lacking mental capacity and therefore unable
      to make an autonomous decision at the time it needs to be made. In this case, a
      'best interests' decision may be made on their behalf, ensuring their wishes and
      beliefs are at the centre of the decision-making process. When making a best
      interests decision, a health practitioner must follow the guidance as set out in
      the MCA legislation to ensure fair and consistent approaches to safeguard and
      provide assurance that the outcome is truly the best decision for the individual.
      This review of the literature supports the findings of a 2014 post-legislative
      review by the House of Lords, which concluded the principles of the MCA are not
      sufficiently embedded into the practice of all health practitioners, due to a
      lack of knowledge, awareness and understanding. However, the evidence base also
      appreciates making a decision on behalf of another person can be a stressful,
      complex and intricate process when further support may be required from the wider
      multidisciplinary team, including potentially seeking legal advice.

PMID- 28767300
TI  - Preventing infection in intravenous catheters in the community.

PMID- 28767301
TI  - Complications of stomas: Their aetiology and management.

PMID- 28767302
TI  - Real world challenges in delivering person-centred care: A community-based case
      study.
AB  - Community nurses face many challenges when trying to practice evidence-based,
      person-centred care. Ongoing concerns regarding the impact of the 2013 Francis
      Report ( Ford and Lintern, 2017 ) suggest that individualised and holistic care
      is an impossible dream, one made harder when the client appears uncooperative.
      This paper presents a case study that sets out how some of these challenges were
      met in a potentially difficult situation experienced by a student nurse and her
      mentor in practice, in which the student was supported to further examine and
      explore issues that may have influenced the situation. In this instance, the
      solution came with the recognition that the client had expertise and knowledge
      that needed to be taken into account, alongside that of the nurses looking after
      him. His care became a partnership, not an imposition of expertise; a principle
      which is transferable to many other situations. Underpinning it was the
      recognition of our shared humanity, wherein lies the essence of truly holistic
      care, and student nurses learning this, through the guidance and support of their
      mentor.

PMID- 28767303
TI  - Nursing care and maintaining professional boundaries.

PMID- 28767304
TI  - Not just a childhood rash: Treating atopic dermatitis in older people.

PMID- 28767305
TI  - Delivering palliative care in a changing world.

PMID- 28767306
TI  - Water, water everywhere but not a drop to drink?

PMID- 28767307
TI  - No more excuses....

PMID- 28767308
TI  - Young carer awareness, identification and referral.
AB  - Young carers often provide care because they have always done so for the people
      they care about, and because they believe that the care recipient could not
      manage without them. For many young carers, looking after their own health,
      combining caring with schoolwork, getting access to training or having time off
      from carer duties can be a major challenge ( Department of Health [DH], 2008 ).
      This paper presents evidence from a literature review that builds a substantial
      body of knowledge to suggest that community nursing teams must develop supportive
      approaches towards increasing an awareness of young carers' needs. Identification
      of young carers by community nurses will encourage referral to appropriate
      services and agencies. The aim of this study was to appraise, for the Queen's
      Nursing Institute, the published evidence base to explore young carers' needs and
      how community nurses could support young carers' needs in England. Databases were
      systematically searched. Title and abstract reviews found 606 potential studies
      (see Figure 1 ), which were identified around topics corresponding to the
      headings of three distinct categories: mental health and wellbeing; education
      needs and resilience; and development of coping strategies. Full-text review
      resulted in 26 publications that met the study's inclusion criteria. The results
      of this work show that there is a scarcity of publications around the community
      nursing needs of young carers. However, studies consistently report young carers
      are hidden from view and have a significant requirement for support and
      information. Therefore, effective ways of delivering community nursing support
      and information to young carers needs to be developed by service providers as a
      matter of priority, and implemented to give the support that young carers need.

PMID- 28767309
TI  - Best Practices for Healthcare Facility and Regional Stockpile Maintenance and
      Sustainment: A Literature Review.
AB  - Preparing for mass casualty incidents is essential to maximizing community
      resilience. Many US-based organizations and regions have developed stockpiles of
      medications, supplies, and equipment for mass casualty incident preparedness. The
      Centers for Disease Control and Prevention (CDC) assess and manage federally
      stockpiled materials, but hospitals, healthcare systems, and regional
      organizations are responsible for maintaining locally owned caches. The CDC has
      protocols for assessing and managing the Strategic National Stockpile, but no
      such guidance exists for local or geographical/regional stockpiles. This article
      outlines best practices and recommendations identified in the literature related
      to maintaining and sustaining a local or regional stockpile. Recommendations are
      provided on the timing and procedures for assessing, inventorying, storing,
      managing, tracking, and deploying materials stockpiled on site, in a trailer, or
      in a warehouse. In addition, alternative approaches for maintaining a local or
      regional cache, such as vendor- or user-managed inventory methods, are addressed.
      Management of local or regional caches requires an investment in infrastructure
      and training but is necessary to ensure the integrity of stockpiled medication
      and supplies and to enable rapid and appropriate activation during a mass
      casualty incident. Hospitals, healthcare systems, businesses, academic
      institutions, public health agencies, organizations, and regions can use the
      recommendations here to develop protocols or policies to properly manage their
      existing stockpiles, which should minimize costs related to damaged supplies.

PMID- 28767311
TI  - How TPX2 helps microtubules branch out.

PMID- 28767310
TI  - Disrupted IRF6-NME1/2 Complexes as a Cause of Cleft Lip/Palate.
AB  - Mutations and common polymorphisms in interferon regulatory factor 6 ( IRF6) are
      associated with both syndromic and nonsyndromic forms of cleft lip/palate (CLP).
      To date, much of the focus on this transcription factor has been on identifying
      its direct targets and the gene regulatory network in which it operates. Notably,
      however, IRF6 is found predominantly in the cytoplasm, with its import into the
      nucleus tightly regulated like other members of the IRF family. To provide
      further insight into the role of IRF6 in the pathogenesis of CLP, we sought to
      identify direct IRF6 protein interactors using a combination of yeast 2-hybrid
      screens and co-immunoprecipitation assays. Using this approach, we identified
      NME1 and NME2, well-known regulators of Rho-type GTPases, E-cadherin endocytosis,
      and epithelial junctional remodeling, as bona fide IRF6 partner proteins. The NME
      proteins co-localize with IRF6 in the cytoplasm of primary palatal epithelial
      cells in vivo, and their interaction with IRF6 is significantly enhanced by
      phosphorylation of key serine residues in the IRF6 C-terminus. Furthermore, CLP
      associated IRF6 missense mutations disrupt the ability of IRF6 to bind the NME
      proteins and result in elevated activation of Rac1 and RhoA, compared to wild
      type IRF6, when ectopically expressed in 293T epithelial cells. Significantly, we
      also report the identification of 2 unique missense mutations in the NME proteins
      in patients with CLP (NME1 R18Q in an IRF6 and GRHL3 mutation-negative patient
      with van der Woude syndrome and NME2 G71V in a patient with nonsyndromic CLP).
      Both variants disrupted the ability of the respective proteins to interact with
      IRF6. The data presented suggest an important role for cytoplasmic IRF6 in
      regulating the availability or localization of the NME1/2 complex and thus the
      dynamic behavior of epithelia during lip/palate development.

PMID- 28767312
TI  - Takeo Ohnishi, PhD, 1944-2017.

PMID- 28767314
TI  - Letters to the Editor.

PMID- 28767313
TI  - Low-Energy Ion-Species-Dependent Induction of DNA Double-Strand Breaks: Ion
      Energy and Fluence Thresholds.
AB  - The goal of this study was to determine the critical ion-radiation conditions
      under which heavy ion beams can induce DNA double-strand breaks. Helium, nitrogen
      and argon-ion beams in the energy range of 20 eV to 2 keV were used to irradiate
      naked DNA plasmid pGFP to fluences of 1, 2 and 4 * 1015 ions/cm2. The topological
      forms of DNA were subsequently analyzed using gel electrophoresis. The DNA forms
      were changed from the original supercoiled to damaged relaxed and linear forms,
      depending on the ion mass, energy, fluence and inertia. We found ion energy and
      fluence thresholds above which direct double-strand breaks can occur. The
      threshold is discussed in terms of the areal ion-energy density and the cross
      section.

PMID- 28767315
TI  - Factors Affecting the Acceptance of Telehealth Services by Heart Failure
      Patients: An Integrative Review.
AB  - BACKGROUND: While telehealth has been shown to improve heart failure patients'
      health outcomes, patients' acceptance of telehealth at the point of referral is
      reported to be low. Little is known about the factors related to patients'
      initial acceptance or refusal of telehealth services. The aim of this review was
      to synthesize evidence on the factors affecting heart failure patients' decision
      making to accept telehealth services in a home setting. METHODS: An integrative
      literature review was conducted. Six electronic databases and three grey
      literature sites were searched. Two reviewers independently reviewed articles for
      inclusion. Articles were included if they reported original data related to the
      acceptance of telehealth services among heart failure patients at home. RESULTS:
      Five studies met the inclusion criteria and were included in the review. Key
      findings indicated that patients generally hold positive views about telehealth.
      Factors that may affect the adoption of telehealth include concerns over
      equipment or technology, concerns over service change, ease-of-use, knowledge of
      the benefits of telehealth, access to care, cost, and privacy. CONCLUSIONS:
      Despite evidence of effectiveness for telehealth, there is a high rate of
      telehealth refusal among patients. Understanding factors associated with heart
      failure patients' decisions regarding telehealth can help healthcare
      organizations structure education programs and other interventions to improve
      acceptance rates.

PMID- 28767317
TI  - Effects of inter-limb asymmetries on physical and sports performance: a
      systematic review.
AB  - The prevalence of inter-limb asymmetries has been reported in numerous studies
      across a wide range of sports and physical qualities; however, few have analysed
      their effects on physical and sports performance. A systematic review of the
      literature was undertaken using the Medline and SPORT Discus databases, with all
      articles required to meet a specified criteria based on a quality review.
      Eighteen articles met the inclusion criteria, relating participant asymmetry
      scores to physical and sports performance measures. The findings of this
      systematic review indicate that inter-limb differences in strength may be
      detrimental to jumping, kicking and cycling performance. When inter-limb
      asymmetries are quantified during jumping based exercises, they have been
      primarily used to examine their association with change of direction speed with
      mixed findings. Inter-limb asymmetries have also been quantified in
      anthropometry, sprinting, dynamic balance and sport-specific actions, again with
      inconsistent findings. However, all results have been reported using associative
      analysis with physical or sport performance metrics with no randomised controlled
      trials included. Further research is warranted to understand the mechanisms that
      underpin inter-limb differences and the magnitude of performance changes that can
      be accounted for by these asymmetries.

PMID- 28767316
TI  - Heritable components of the human fecal microbiome are associated with visceral
      fat.
AB  - Obesity and its associated diseases are one of the major causes of death
      worldwide. The gut microbiota has been identified to have essential regulatory
      effects on human metabolism and obesity in particular. In a recent study we
      provided some insights into the link between the gut microbiota (GM) and
      adiposity, as well as host genetic modulation of these processes. Our results
      identify novel evidence of association between 6 adiposity phenotypes and faecal
      microbial operational taxonomic units (OTUs). Accumulation of visceral fat, a key
      risk factor for cardio-metabolic disease, has the strongest and most pervasive
      signature on the gut microbiota of the factors we examined. Furthermore, we
      observe that the adiposity-associated OTUs were classified as heritable and in
      some cases were also associated with host genetic variation at obesity-associated
      human candidate genes FHIT, TDRG1 and ELAVL4. This addendum confirms our
      previously published results in the TwinsUK cohort using a different approach to
      OTU clustering and multivariate analysis, and discusses further the importance of
      considering the GM as a complex ecosystem.

PMID- 28767318
TI  - The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma
      Related Disorders.
AB  - Biological psychiatry research has long focused on the brain in elucidating the
      neurobiological mechanisms of anxiety- and trauma-related disorders. This review
      challenges this assumption and suggests that the gut microbiome and its
      interactome also deserve attention to understand brain disorders and develop
      innovative treatments and diagnostics in the 21st century. The recent, in-depth
      characterization of the human microbiome spurred a paradigm shift in human health
      and disease. Animal models strongly suggest a role for the gut microbiome in
      anxiety- and trauma-related disorders. The microbiota-gut-brain (MGB) axis sits
      at the epicenter of this new approach to mental health. The microbiome plays an
      important role in the programming of the hypothalamic-pituitary-adrenal (HPA)
      axis early in life, and stress reactivity over the life span. In this review, we
      highlight emerging findings of microbiome research in psychiatric disorders,
      focusing on anxiety- and trauma-related disorders specifically, and discuss the
      gut microbiome as a potential therapeutic target. 16S rRNA sequencing has enabled
      researchers to investigate and compare microbial composition between individuals.
      The functional microbiome can be studied using methods involving metagenomics,
      metatranscriptomics, metaproteomics, and metabolomics, as discussed in the
      present review. Other factors that shape the gut microbiome should be considered
      to obtain a holistic view of the factors at play in the complex interactome
      linked to the MGB. In all, we underscore the importance of microbiome science,
      and gut microbiota in particular, as emerging critical players in mental illness
      and maintenance of mental health. This new frontier of biological psychiatry and
      postgenomic medicine should be embraced by the mental health community as it
      plays an ever-increasing transformative role in integrative and holistic health
      research in the next decade.

PMID- 28767319
TI  - Systematic Review and Meta-Analysis of the Utilization of Ethanol Locks in
      Pediatric Patients With Intestinal Failure.
AB  - BACKGROUND: Intestinal failure is a chronic condition related to loss of bowel
      length and/or function, resulting in dependence on central venous catheters for
      fluids and nutrition. Catheter use can be associated with significant
      complications, including catheter-related bloodstream infections (CRBSIs), which
      can lead to loss of vascular access, advancing intestinal failure associated
      liver disease and death. Our objective was to evaluate the effectiveness and
      safety of ethanol locks as compared with standard heparin locks in pediatric
      intestinal failure. METHODS: Databases, including MEDLINE and EMBASE, were
      searched until March 2017. Titles and abstracts were reviewed independently and
      relevant articles reassessed by full-text review. The main outcome was the rate
      of CRBSIs, while secondary outcomes were catheter replacement and repair.
      RESULTS: Nine observational studies were included. The mean difference in rate of
      CRBSIs was 6.27 per 1000 catheter days (95% CI, 4.89-7.66) favoring ethanol
      locks, with a 63% overall reduction in infection rate. The mean difference in
      catheter replacement rate (per 1000 catheter days) was 4.56 (95% Cl, 2.68-6.43)
      favoring ethanol locks. The overall effect on catheter repair rate (per 1000
      catheter days) was -1.67 (95% CI, -2.30 to -1.05), indicating lower repair rate
      with heparin locks. CONCLUSION: Sufficient evidence was noted showing that
      ethanol locks reduced CRBSIs and catheter replacements. Our findings raise
      questions about the effect of the ethanol lock on catheter integrity based on the
      noted increase in repair rate. This requires further prospective evaluation and
      may support selective application of ethanol locks to patients with documented
      CRBSIs.

PMID- 28767321
TI  - Does elite success trigger mass participation in table tennis? An analysis of
      trickle-down effects in Germany, France and Austria.
AB  - There is a widespread belief that success at the elite level leads to increasing
      mass participation in sports. However, this assumption is merely supported by
      empirical evidence and is analyzed here for the case of table tennis. Therefore
      long-term data (1964-2014) on participation in Germany, France and Austria is
      statistically tested for effects of success by the countries' athletes at
      international competitions. Results indicate that no general trickle-down effect
      can be confirmed for table tennis in the countries observed. Rather, findings are
      ambivalent, as a strong positive effect was found for the Austrian case, but a
      paradox relation for the German case, where elite success has been accompanied by
      decreasing participation in the last decades. Accordingly, as an "automatic"
      trickle-down effect is unlikely, more specific analyses and strategies seem
      necessary to use elite success as a lever for the promotion of the sport.

PMID- 28767322
TI  - ANTHRAX IN THE MACKENZIE WOOD BISON (BISON BISON ATHABASCAE) POPULATION: 2012
      ANTHRAX OUTBREAK AND HISTORICAL EXPOSURE IN NONOUTBREAK YEARS.
AB  - Anthrax, caused by the spore-forming bacterium Bacillus anthracis, poses a threat
      to wood bison (Bison bison athabascae) conservation. We used descriptive
      epidemiology to characterize a large outbreak of anthrax in the Mackenzie bison
      population in the Northwest Territories, Canada, in 2012 and investigated
      historical serologic exposure of the bison to the bacterium in nonoutbreak years.
      Between late June and early August 2012, 451 bison carcasses were detected;
      mortality peaked from 13-19 July. A substantial number of calves, yearlings, and
      adult females died in the 2012 outbreak, unlike in two previous anthrax outbreaks
      in this population that killed mostly mature males. On the basis of the
      difference in estimates of population size prior to the outbreak (2012) and after
      the outbreak (2013), it is possible that not all dead bison were found during the
      outbreak. We assessed serologic history of exposure to B. anthracis by using
      samples from the Mackenzie wood bison population collected between 1986 and 2009.
      Overall, 87 of 278 samples were positive (31%). Seroprevalence was lower in
      females (18%, 10/55) than males (36%, 72/203). The highest proportion of positive
      submissions (90%) was from 1994, the year following the only anthrax outbreak
      within the historical data set. Both adult males and females had a higher
      likelihood of being seropositive than the younger age categories. There was a
      trend toward declining antibody levels between the 1993 and 2012 outbreak years.

PMID- 28767320
TI  - Forkhead Box M1 positively regulates UBE2C and protects glioma cells from
      autophagic death.
AB  - Ubiquitin-conjugating enzyme E2C (UBE2C) is characterized as a crucial molecule
      in cancer cell growth that plays an essential role in the development of gliomas,
      but the detailed mechanisms have not been fully elucidated. In this study, we
      found that Forkhead box transcription factor M1 (FoxM1) overexpression increased
      UBE2C expression, whereas FoxM1 suppression inhibited UBE2C expression in glioma
      cells. In addition, high FoxM1/UBE2C expression was significantly correlated with
      poor prognosis in glioma. We subsequently demonstrated that UBE2C was a direct
      transcriptional target of FoxM1, and site-directed mutations markedly down
      regulated UBE2C promoter activity. Moreover, UBE2C siRNA (si-UBE2C) significantly
      induced glioma cell autophagy and increased both mCherry-LC3 punctate
      fluorescence and LC3B-II/LC3-I expression. Notably, the si-UBE2C-induced decrease
      in cell viability was markedly inhibited by the autophagy inhibitor bafilomycin
      A1. The silencing of UBE2C resulted in a distinct inhibition of the PI3K-Akt-mTOR
      pathway, which functions in the negative modulation of autophagy. Collectively,
      our findings provide clinical and molecular evidence that FoxM1 promotes glioma
      progression by enhancing UBE2C transcription and that the inhibition of UBE2C
      partially induces autophagic glioma cell death. Thus, targeting the FoxM1-UBE2C
      axis has therapeutic potential in the treatment of gliomas.

PMID- 28767324
TI  - eEF2K protects MYCN-amplified cells from starvation.

PMID- 28767323
TI  - Candidate Genes for Nonsyndromic Cleft Palate Detected by Exome Sequencing.
AB  - Nonsyndromic cleft palate only (nsCPO) is a facial malformation that has a
      livebirth prevalence of 1 in 2,500. Research suggests that the etiology of nsCPO
      is multifactorial, with a clear genetic component. To date, genome-wide
      association studies have identified only 1 conclusive common variant for nsCPO,
      that is, a missense variant in the gene grainyhead-like-3 ( GRHL3). Thus, the
      underlying genetic causes of nsCPO remain largely unknown. The present study
      aimed at identifying rare variants that might contribute to nsCPO risk, via whole
      exome sequencing (WES), in multiply affected Central European nsCPO pedigrees.
      WES was performed in 2 affected first-degree relatives from each family. Variants
      shared between both individuals were analyzed for their potential deleterious
      nature and a low frequency in the general population. Genes carrying promising
      variants were annotated for 1) reported associations with facial development, 2)
      multiple occurrence of variants, and 3) expression in mouse embryonic palatal
      shelves. This strategy resulted in the identification of a set of 26 candidate
      genes that were resequenced in 132 independent nsCPO cases and 623 independent
      controls of 2 different ethnicities, using molecular inversion probes. No rare
      loss-of-function mutation was identified in either WES or resequencing step.
      However, we identified 2 or more missense variants predicted to be deleterious in
      each of 3 genes ( ACACB, PTPRS, MIB1) in individuals from independent families.
      In addition, the analyses identified a novel variant in GRHL3 in 1 patient and a
      variant in CREBBP in 2 siblings. Both genes underlie different syndromic forms of
      CPO. A plausible hypothesis is that the apparently nonsyndromic clefts in these 3
      patients might represent hypomorphic forms of the respective syndromes. In
      summary, the present study identified rare variants that might contribute to
      nsCPO risk and suggests candidate genes for further investigation.

PMID- 28767325
TI  - Evolutionary Relationships and Cytotaxonomy Considerations in the Genus
      Pyrrhulina (Characiformes, Lebiasinidae).
AB  - Although fishes exhibit the greatest biodiversity among the vertebrates, a large
      percentage of this fauna is still underexplored on evolutionary cytogenetic
      questions, particularly the miniature species. The Lebiasinidae family is a
      particular example for such case. This study is the first one presenting
      differential cytogenetic methods, such as C-banding, repetitive DNAs mapping,
      comparative genomic hybridization (CGH), and whole chromosome painting in
      lebiasinid species. Pyrrhulina australis and Pyrrhulina aff. australis were
      deeply investigated concerning their chromosomal patterns and evolutionary
      relationships. These species have a very similar morphology, but they can be
      distinguished by a longitudinal midlateral faintly dark stripe exclusive for
      Pyrrhulina aff. australis. Both species presented 2n = 40 chromosomes (4st +36a),
      without heteromorphic sex chromosomes. However, despite their morphological and
      karyotype resemblance, it was evidenced that both species have already gone
      through a significant genomic divergence, thus corresponding to distinct
      evolutionary units. Furthermore, to give additional support to some proposals on
      evolutionary relationship among Lebiasinidae with other fish families, a
      chromosomal comparative approach with Erythrinus erythrinus, a representative
      species of the Erythrinidae family, was also performed. In addition to have
      similar karyotype structure, mainly composed by acrocentric chromosomes, both
      species share uncommon genomic similarities, such as (i) syntenic location of 5S
      and 18S rDNA sequences; (ii) huge dispersion of multiple 5S rDNA sites in the
      karyotypes; and (iii) complex association between 5S rDNA and Rex3 elements. CGH
      experiments, despite reinforcing some shared genomic homologies, also highlighted
      that both Pyrrhulina and Erythrinus have a range of nonoverlapping species
      specific signals. The overall chromosomal data proved to be effective markers for
      the cytotaxonomy and evolutionary process among Lebiasinidae fishes.

PMID- 28767326
TI  - Tracking of Indels by DEcomposition is a Simple and Effective Method to Assess
      Efficiency of Guide RNAs in Zebrafish.
AB  - A bottleneck in CRISPR/Cas9 genome editing is variable efficiencies of in silico
      designed gRNAs. We evaluated the sensitivity of the TIDE method (Tracking of
      Indels by DEcomposition) introduced by Brinkman et al. in 2014 for assessing the
      cutting efficiencies of gRNAs in zebrafish. We show that this simple method,
      which involves bulk polymerase chain reaction amplification and Sanger
      sequencing, is highly effective in tracking well-performing gRNAs in pools of
      genomic DNA derived from injected embryos. The method is equally effective for
      tracing INDELs in heterozygotes.

PMID- 28767329
TI  - Corrigendum.

PMID- 28767327
TI  - A Note from the Managing Editor to A Managing Editor: Remembering Gloria Parloff
      1913-2017.

PMID- 28767331
TI  - Unraveling the Role of Loneliness in Depression: The Relationship Between Daily
      Life Experience and Behavior.
AB  - OBJECTIVE: Focusing on temporal associations between momentary (or state)
      loneliness, appraisal of social company, and being alone in daily life may help
      elucidate mechanisms that contribute to the development of prolonged (or trait)
      loneliness and major depressive disorder (MDD). We aim to examine if (a) a self
      reinforcing loop between loneliness, negative appraisals of social company, and
      being alone in daily life may contribute to trait loneliness; (b) this possible
      self-reinforcing loop may also contribute to the development of MDD, by testing
      differences in temporal relationships between these social elements in
      participants who did or did not develop MDD during follow-up; and (c) any of
      these social elements at baseline predicted a MDD at follow-up. METHODS: A female
      general population sample (n = 417) participated in an experience sampling method
      (ESM) study. Time-lagged analyses between loneliness, appraisal of social
      company, and being alone were examined at baseline, and their associations with
      the development of MDD during 20 months follow-up were investigated. RESULTS:
      State loneliness was followed by an increase in negative appraisals of social
      company and a higher frequency of being alone. Further, negative appraisals of
      social company were associated with a higher frequency of being alone afterward.
      Only the latter was significant in the transition to MDD group. Trait loneliness
      predicted MDD during follow-up. CONCLUSIONS: Avoiding social contact after
      appraising company more negatively may contribute to the development of MDD.

PMID- 28767332
TI  - Short-Term Group Therapy for Complicated Grief: The Relationship Between
      Patients' In-Session Reflection and Outcome.
AB  - OBJECTIVE: The objective of the present study was to examine the nature of
      patients' work in two types of short-term group psychotherapy. The study sought
      to investigate the relationship between patients' psychodynamic work versus
      supportive work in group psychotherapy and treatment outcome at termination and
      at 6-month follow-up. Psychodynamic work refers to reflection regarding
      intrapsychic motivations, defenses, and relational patterns, and supportive work
      refers to practical problem solving. METHOD: Participants were 110 patients who
      completed two forms of group therapy for complicated grief: interpretive therapy
      and supportive therapy. Two types of patients' in-session activity-psychodynamic
      work and supportive work-were rated by group therapists in both treatments. Pre
      post and follow-up outcome domains included general symptoms, grief symptoms, and
      life dissatisfaction/severity of target objectives. RESULTS: There was no
      significant difference in the nature of patients' therapeutic work between
      interpretive and supportive groups. Psychodynamic work was associated with pre
      post improvement in grief symptoms. Psychodynamic work was also associated with
      further improvement in grief symptoms at 6-month follow-up, along with
      improvement in broader symptom domains. Supportive work was not associated with
      any pre-post or follow-up benefit. CONCLUSION: The findings provide evidence that
      psychodynamic work-focused on the development of insight and self-reflection-in
      group psychotherapy can contribute to further benefit after the completion of
      treatment. This finding cut across two approaches to short-term group therapy for
      complicated grief, suggesting that it may reflect a general curative mechanism of
      group treatments.

PMID- 28767333
TI  - Leaving Distress Behind: A Randomized Controlled Study on Change in Emotional
      Processing in Borderline Personality Disorder.
AB  - OBJECTIVE: The marked impulsivity and instability of clients suffering from
      borderline personality disorder (BPD) greatly challenge therapists' understanding
      and responsiveness. This may hinder the development of a constructive therapeutic
      relationship despite it being of particular importance in their treatment. Recent
      studies have shown that using motive-oriented therapeutic relationship (MOTR), a
      possible operationalization of appropriate therapist responsiveness, can enhance
      treatment outcome for BPD. The overall objective of this study is to examine
      change in emotional processing in BPD clients following the therapist's use of
      MOTR. METHOD: The present paper focuses on N = 50 cases, n = 25 taken from each
      of two conditions of a randomized controlled add-on effectiveness design. Clients
      were either allocated to a manual-based psychiatric-psychodynamic 10-session
      version of general psychiatric management (GPM), a borderline-specific treatment,
      or to a 10-session version of GPM augmented with MOTR. Emotional states were
      assessed using the Classification of Affective-Meaning States (Pascual-Leone &
      Greenberg, 2005) at intake, midtreatment, and in the penultimate session.
      RESULTS: Across treatment, early expressions of distress, especially the emotion
      state of global distress, were shown to significantly decrease (p = .00), and
      adaptive emotions were found to emerge (p < .05). Between-condition differences
      of change were found, including a significant increase in emotional variability
      and stronger outcome predictors in the MOTR condition. CONCLUSIONS: The findings
      indicate initial emotional change in BPD clients in a relatively short time frame
      and suggest the addition of MOTR to psychotherapeutic treatments as promising.
      Clinical implications are discussed.

PMID- 28767335
TI  - Role of Pain-Based Catastrophizing in Pain, Disability, Distress, and Suicidal
      Ideation.
AB  - BACKGROUND: In chronic pain, patients' coping affects their adaptation. In two
      studies, we examined the role of pain catastrophizing, a maladaptive coping
      strategy, in pain, distress, and disability. In Study 2 we compared
      catastrophizing to pain acceptance and to other coping strategies. METHODS: Study
      1. Chronic pain patients (N = 428) were assessed four times as to their pain,
      disability, catastrophizing, and distress (depression and anxiety). Study 2.
      Patients (N = 165) were assessed as to coping and pain acceptance, pain, related
      distress, depression, hope, suicidal ideations, perceived burdensomeness, and
      thwarted belongingness. RESULTS: Study 1. A Structural Equation Modeling (SEM)
      analysis revealed that Time 1 Pain-based catastrophizing prospectively predicted
      pain (beta =.36, p < .001). Distress prospectively predicted pain related
      disability (beta = .34, p <.001). Study 2. Pain-based catastrophizing predicted
      sensory pain (beta = .22, p = .018), depression (beta = .43, p < .001), and
      suicidal ideation (O.R. = 1.88), which were also predicted by depression and
      perceived burdensomeness. Distraction predicted sensory pain (beta = .21, p =
      .017, respectively). Activity engagement predicted low levels of depression (beta
      = -.29, p < .001, respectively), and willingness to accept pain predicted low
      pain-related distress (beta = -.16, p = .05). CONCLUSIONS: Pain catastro-phizing
      and pain acceptance constitute risk and resilience factors. Both should be
      assessed and targeted in pain management.

PMID- 28767336
TI  - Advances in Scientific Possibilities Offered by Real-Time Monitoring Technology.
AB  - There has been a marked increase in research aimed at studying dynamic (e.g., day
      to-day, moment-to-moment) changes in mental disorders and related behavior
      problems. Indeed, the number of scientific papers published that focus on real
      time monitoring has been nearly doubling every five years for the past several
      decades. These methods allow for a more fine-grained description of phenomena of
      interest as well as for real-world tests of theoretical models of human behavior.
      Here we comment on the recent study by van Winkel and colleagues (this issue)as
      an excellent example of the use of real-time monitoring methods to better
      understand mental disorders. We also discuss the expanding universe of new
      technologies (e.g., smartphones, wearable biosensors) that can be used to make
      discoveries about psychopathology and related constructs and describe what we
      perceive to be some of the most exciting scientific possibilities that can be
      achieved in the near term by taking advantage of these new and rapidly developing
      tools.

PMID- 28767337
TI  - Prevalence and Course of Symptom-Defined PTSD in Individuals Directly or
      Indirectly Exposed to Terror: A Longitudinal Study.
AB  - OBJECTIVE: It is well established that direct exposure to terrorism can result in
      posttraumatic stress disorder (PTSD). However, individuals indirectly exposed to
      terrorism may also develop symptoms of PTSD. This study examined the prevalence
      and course of symptom-defined PTSD in employees who were present and not present
      at the site of a workplace terror attack. METHODS: Survey data from ministerial
      employees were collected 10, 22, and 34 months after the 2011 bombing in the
      government district of Oslo. A total of 3,520 employees were initially invited to
      the study. Response rates of eligible participants were 56% (N = 1,974) at T1,
      55% (N = 1,780) at T2, and 54% (N = 1,578) at T3. PTSD was measured using the
      Post-traumatic Stress Disorder Checklist-Specific (PCL-S). Symptom-defined PTSD
      was specified as meeting the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision (DSM-IV-TR), B, C, and D criteria.
      RESULTS: Our findings showed a low and declining prevalence of symptom-defined
      PTSD in employees indirectly exposed to a workplace terror attack (4%, 3%, and 2%
      at the three respective times). In employees present at the site of the
      explosion, PTSD was six- to eightfold more prevalent (24%, 17%, and 17%).
      CONCLUSIONS: Individuals indirectly exposed to terrorism may develop long-lasting
      posttraumatic stress reactions fulfilling PTSD symptom criteria. Due to the large
      number of individuals that may be indirectly exposed to terrorism, even a low
      risk of PTSD may result in high numbers of individuals with substantial
      posttraumatic stress. Our findings have implications for the planning and
      implementation of health care services beyond those directly exposed after large
      scale terror events.

PMID- 28767338
TI  - Intensive Evening Outpatient Treatment for Patients With Personality Dysfunction:
      Early Group Process, Change in Interpersonal Distress, and Longer-Term Social
      Functioning.
AB  - OBJECTIVE: Entrenched interpersonal difficulties are a defining feature of those
      with personality dysfunction. Evening treatment-a comprehensive and intensive
      group-oriented outpatient therapy program-offers a unique approach to delivering
      mental health services to patients with chronic personality dysfunction. This
      study assessed change in interpersonal problems as a key outcome, the relevance
      of such change to future social functioning, and the influence of early group
      processes on this change. METHOD: Consecutively admitted patients (N = 75) to a
      group-oriented evening treatment program were recruited; the majority were
      diagnosed with personality disorder. Therapy outcome was represented by scores on
      the Inventory of Interpersonal Problems. Follow-up outcome was represented by the
      global score of the Social Adjustment Scale. Group climate, group cohesion, and
      the therapeutic alliance were examined as process variables. RESULTS: Patients
      experienced substantial reduction in distress associated with interpersonal
      problems; early process factors that reflected a cohesive and engaged group
      climate and stronger therapeutic alliance were predictive of this outcome.
      Improvement in interpersonal distress was predictive of global social functioning
      six months later. The therapeutic alliance most strongly accounted for change in
      interpersonal problems at posttreatment and social functioning at follow-up.
      CONCLUSIONS: A comprehensive and integrated outpatient group therapy program,
      offered in the evening to accommodate patients' real-life demands, can facilitate
      considerable improvement in interpersonal problems, which in turn influences
      later social functioning. The intensity and intimacy of peer interactions in the
      therapy groups, and a strong alliance with the program therapists, are likely
      interacting factors that are particularly important to facilitate such change.

PMID- 28767340
TI  - All That Wheezes....

PMID- 28767339
TI  - Assessing gut microbiota perturbations during the early phase of infectious
      diarrhea in Vietnamese children.
AB  - Diarrheal diseases remain the second most common cause of mortality in young
      children in developing countries. Efforts have been made to explore the impact of
      diarrhea on bacterial communities in the human gut, but a thorough understanding
      has been impeded by inadequate resolution in bacterial identification and the
      examination of only few etiological agents. Here, by profiling an extended region
      of the 16S rRNA gene in the fecal microbiome, we aimed to elucidate the nature of
      gut microbiome perturbations during the early phase of infectious diarrhea caused
      by various etiological agents in Vietnamese children. Fecal samples from 145
      diarrheal cases with a confirmed infectious etiology before antimicrobial therapy
      and 54 control subjects were analyzed. We found that the diarrheal fecal
      microbiota could be robustly categorized into 4 microbial configurations that
      either generally resembled or were highly divergent from a healthy state. Factors
      such as age, nutritional status, breastfeeding, and the etiology of the infection
      were significantly associated with these microbial community structures. We
      observed a consistent elevation of Fusobacterium mortiferum, Escherichia, and
      oral microorganisms in all diarrheal fecal microbiome configurations, proposing
      similar mechanistic interactions, even in the absence of global dysbiosis. We
      additionally found that Bifidobacterium pseudocatenulatum was significantly
      depleted during dysenteric diarrhea regardless of the etiological agent,
      suggesting that further investigations into the use of this species as a
      dysentery-orientated probiotic therapy are warranted. Our findings contribute to
      the understanding of the complex influence of infectious diarrhea on gut
      microbiome and identify new opportunities for therapeutic interventions.

PMID- 28767341
TI  - Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.

PMID- 28767342
TI  - End-of-Life Decisions in the Netherlands over 25 Years.

PMID- 28767343
TI  - Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation.

PMID- 28767344
TI  - Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation.

PMID- 28767346
TI  - Arteriovenous Malformations of the Brain.

PMID- 28767347
TI  - Arteriovenous Malformations of the Brain.

PMID- 28767348
TI  - Potential Pitfall of Pluripotent Stem Cells.

PMID- 28767350
TI  - Gabapentin and Pregabalin for Pain - Is Increased Prescribing a Cause for
      Concern?

PMID- 28767349
TI  - IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.
AB  - BACKGROUND: Donor-specific antibodies create an immunologic barrier to
      transplantation. Current therapies to modify donor-specific antibodies are
      limited and ineffective in the most highly HLA-sensitized patients. The IgG
      degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase,
      cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent
      cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that
      IdeS might be useful for desensitization. We report on the combined experience of
      two independently performed open-label, phase 1-2 trials (conducted in Sweden and
      the United States) that assessed the efficacy of IdeS with regard to
      desensitization and transplantation of a kidney from an HLA-incompatible donor.
      METHODS: We administered IdeS to 25 highly HLA-sensitized patients (11 patients
      in Uppsala or Stockholm, Sweden, and 14 in Los Angeles) before the
      transplantation of a kidney from an HLA-incompatible donor. Frequent monitoring
      for adverse events, outcomes, donor-specific antibodies, and renal function was
      performed, as were renal biopsies. Immunosuppression after transplantation
      consisted of tacrolimus, mycophenolate mofetil, and glucocorticoids. Patients in
      the U.S. study also received intravenous immune globulin and rituximab after
      transplantation to prevent antibody rebound. RESULTS: Recipients in the U.S.
      study had a significantly longer cold ischemia time (the time elapsed between
      procurement of the organ and transplantation), a significantly higher rate of
      delayed graft function, and significantly higher levels of class I donor-specific
      antibodies than those in the Swedish study. A total of 38 serious adverse events
      occurred in 15 patients (5 events were adjudicated as being possibly related to
      IdeS). At transplantation, total IgG and HLA antibodies were eliminated. A total
      of 24 of 25 patients had perfusion of allografts after transplantation. Antibody
      mediated rejection occurred in 10 patients (7 patients in the U.S. study and 3 in
      the Swedish study) at 2 weeks to 5 months after transplantation; all these
      patients had a response to treatment. One graft loss, mediated by non-HLA IgM and
      IgA antibodies, occurred. CONCLUSIONS: IdeS reduced or eliminated donor-specific
      antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients.
      (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 ,
      and NCT02475551 .).

PMID- 28767351
TI  - Acute Kidney Injury in Patients with Cancer.

PMID- 28767352
TI  - Acute Kidney Injury in Patients with Cancer.

PMID- 28767353
TI  - Crusted Scabies.

PMID- 28767354
TI  - Xanthomas in Familial Hypercholesterolemia.

PMID- 28767355
TI  - A Bacterial IgG-Degrading Enzyme to Unhinge Antibodies.

PMID- 28767356
TI  - Angiotensin II for the Treatment of Vasodilatory Shock - Promise and Caution.

PMID- 28767357
TI  - Evidence for Health Decision Making - Beyond Randomized, Controlled Trials.

PMID- 28767358
TI  - Monitoring Avian Influenza Viruses from Chicken Carcasses Sold at Markets, China,
      2016.
AB  - During 2016 in Guangzhou, China, we detected infectious avian influenza viruses
      (AIVs) in 39.8% of samples from chicken carcasses slaughtered at live poultry
      markets but none from carcasses supplied to supermarkets by facilities bypassing
      live poultry markets. Promoting supply chains with high biosecurity may reduce
      the risk for zoonotic AIV transmission.

PMID- 28767359
TI  - An EOG-Based Human-Machine Interface for Wheelchair Control.
AB  - OBJECTIVE: Nonmanual human-machine interfaces (HMIs) have been studied for
      wheelchair control with the aim of helping severely paralyzed individuals regain
      some mobility. The challenge is to rapidly, accurately, and sufficiently produce
      control commands, such as left and right turns, forward and backward motions,
      acceleration, deceleration, and stopping. In this paper, a novel electrooculogram
      (EOG) based HMI is proposed for wheelchair control. METHODS: A total of 13
      flashing buttons, each of which corresponds to a command, are presented in the
      graphical user interface. These buttons flash on a one-by-one manner in a
      predefined sequence. The user can select a button by blinking in sync with its
      flashes. The algorithm detects the eye blinks from a channel of vertical EOG data
      and determines the user's target button based on the synchronization between the
      detected blinks and the button's flashes. RESULTS: For healthy subjects/patients
      with spinal cord injuries, the proposed HMI achieved an average accuracy of 96.7%
      / 91.7% and a response time of 3.53 s/3.67 s with 0 false positive rates (FPRs).
      CONCLUSION: Using one channel of vertical EOG signals associated with eye blinks,
      the proposed HMI can accurately provide sufficient commands with a satisfactory
      response time. SIGNIFICANCE: The proposed HMI provides a novel nonmanual approach
      for severely paralyzed individuals to control a wheelchair. Compared with a newly
      established EOG-based HMI, the proposed HMI can generate more commands with
      higher accuracy, lower FPR, and fewer electrodes.

PMID- 28767360
TI  - Software Toolbox for Low-Frequency Conductivity and Current Density Imaging Using
      MRI.
AB  - OBJECTIVE: Low-frequency conductivity and current density imaging using MRI
      includes magnetic resonance electrical impedance tomography (MREIT), diffusion
      tensor MREIT (DT-MREIT), conductivity tensor imaging (CTI), and magnetic
      resonance current density imaging (MRCDI). MRCDI and MREIT provide current
      density and isotropic conductivity images, respectively, using current-injection
      phase MRI techniques. DT-MREIT produces anisotropic conductivity tensor images by
      incorporating diffusion weighted MRI into MREIT. These current-injection
      techniques are finding clinical applications in diagnostic imaging and also in
      transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and
      electroporation where treatment currents can function as imaging currents. To
      avoid adverse effects of nerve and muscle stimulations due to injected currents,
      conductivity tensor imaging (CTI) utilizes B1 mapping and multi-b diffusion
      weighted MRI to produce low-frequency anisotropic conductivity tensor images
      without injecting current. This paper describes numerical implementations of
      several key mathematical functions for conductivity and current density image
      reconstructions in MRCDI, MREIT, DT-MREIT, and CTI. METHODS: To facilitate
      experimental studies of clinical applications, we developed a software toolbox
      for these low-frequency conductivity and current density imaging methods. This MR
      based conductivity imaging (MRCI) toolbox includes 11 toolbox functions which can
      be used in the MATLAB environment. RESULTS: The MRCI toolbox is available at
      http://iirc.khu.ac.kr/software.html . Its functions were tested by using several
      experimental datasets, which are provided together with the toolbox. CONCLUSION:
      Users of the toolbox can focus on experimental designs and interpretations of
      reconstructed images instead of developing their own image reconstruction
      softwares. We expect more toolbox functions to be added from future research
      outcomes. OBJECTIVE: Low-frequency conductivity and current density imaging using
      MRI includes magnetic resonance electrical impedance tomography (MREIT),
      diffusion tensor MREIT (DT-MREIT), conductivity tensor imaging (CTI), and
      magnetic resonance current density imaging (MRCDI). MRCDI and MREIT provide
      current density and isotropic conductivity images, respectively, using current
      injection phase MRI techniques. DT-MREIT produces anisotropic conductivity tensor
      images by incorporating diffusion weighted MRI into MREIT. These current
      injection techniques are finding clinical applications in diagnostic imaging and
      also in transcranial direct current stimulation (tDCS), deep brain stimulation
      (DBS), and electroporation where treatment currents can function as imaging
      currents. To avoid adverse effects of nerve and muscle stimulations due to
      injected currents, conductivity tensor imaging (CTI) utilizes B1 mapping and
      multi-b diffusion weighted MRI to produce low-frequency anisotropic conductivity
      tensor images without injecting current. This paper describes numerical
      implementations of several key mathematical functions for conductivity and
      current density image reconstructions in MRCDI, MREIT, DT-MREIT, and CTI.
      METHODS: To facilitate experimental studies of clinical applications, we
      developed a software toolbox for these low-frequency conductivity and current
      density imaging methods. This MR-based conductivity imaging (MRCI) toolbox
      includes 11 toolbox functions which can be used in the MATLAB environment.
      RESULTS: The MRCI toolbox is available at http://iirc.khu.ac.kr/software.html .
      Its functions were tested by using several experimental datasets, which are
      provided together with the toolbox. CONCLUSION: Users of the toolbox can focus on
      experimental designs and interpretations of reconstructed images instead of
      developing their own image reconstruction softwares. We expect more toolbox
      functions to be added from future research outcomes.

PMID- 28767361
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 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. Of all the tissue
      parameters, perfusion was found to affect the heating the most. 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 which patient specific pretreatment calculations could be used to overcome the
      aberration and therefore make ultrasound treatment possible.

PMID- 28767362
TI  - Modeling of Stretch Reflex Activation Considering Muscle Type.
AB  - Although the stretch reflex plays an important role in spasticity, so far the
      stretch reflex has not been sufficiently investigated. Previous stretch reflex
      activation models have some limitations, whereby they are not able to predict
      outcomes of some stretch reflex cases and do not consider uneven distribution of
      muscle length and stretch velocity on reflex activation. The purpose of this
      study was: 1) to develop a modified stretch reflex activation model employing a
      new muscle length threshold and weighting factors for slow-twitch fiber and fast
      twitch fiber, and 2) to validate the model using pendulum experiments of the
      lower and upper limbs. The new muscle length threshold was defined using the
      optimal muscle fiber length. Based on the optimal fiber length, the new threshold
      allows for prediction of the stretch reflex activation at muscle lengths shorter
      than have been possible with previous models. The muscle type weighting factors
      realized unequal contributions between the muscle length and stretch velocity. We
      proved the validity of the proposed reflex activation model by using pendulum
      tests to induce patellar tendon and biceps brachii reflexes. Unknown parameters
      employed in the proposed model were obtained by minimizing differences in motion
      obtained with the proposed model and experiments. The proposed model can predict
      stretch reflex activation at shorter muscle lengths. In addition, the proposed
      model reflected nonhomogeneous characteristics related to the unequal
      contributions between muscle length and stretch velocity. As a result, patellar
      tendon and biceps brachii reflex phenomena were shown to be predicted more
      accurately in this study.

PMID- 28767363
TI  - Robust Online Matrix Factorization for Dynamic Background Subtraction.
AB  - We propose an effective online background subtraction method, which can be
      robustly applied to practical videos that have variations in both foreground and
      background. Different from previous methods which often model the foreground as
      Gaussian or Laplacian distributions, we model the foreground for each frame with
      a specific mixture of Gaussians (MoG) distribution, which is updated online frame
      by frame. Particularly, our MoG model in each frame is regularized by the learned
      foreground/background knowledge in previous frames. This makes our online MoG
      model highly robust, stable and adaptive to practical foreground and background
      variations. The proposed model can be formulated as a concise probabilistic MAP
      model, which can be readily solved by EM algorithm. We further embed an affine
      transformation operator into the proposed model, which can be automatically
      adjusted to fit a wide range of video background transformations and make the
      method more robust to camera movements. With using the sub-sampling technique,
      the proposed method can be accelerated to execute more than 250 frames per second
      on average, meeting the requirement of real-time background subtraction for
      practical video processing tasks. The superiority of the proposed method is
      substantiated by extensive experiments implemented on synthetic and real videos,
      as compared with state-of-the-art online and offline background subtraction
      methods.

PMID- 28767364
TI  - Learning Spatial-Semantic Context with Fully Convolutional Recurrent Network for
      Online Handwritten Chinese Text Recognition.
AB  - Online handwritten Chinese text recognition (OHCTR) is a challenging problem as
      it involves a large-scale character set, ambiguous segmentation, and variable
      length input sequences. In this paper, we exploit the outstanding capability of
      path signature to translate online pen-tip trajectories into informative
      signature feature maps, successfully capturing the analytic and geometric
      properties of pen strokes with strong local invariance and robustness. A multi
      spatial-context fully convolutional recurrent network (MC-FCRN) is proposed to
      exploit the multiple spatial contexts from the signature feature maps and
      generate a prediction sequence while completely avoiding the difficult
      segmentation problem. Furthermore, an implicit language model is developed to
      make predictions based on semantic context within a predicting feature sequence,
      providing a new perspective for incorporating lexicon constraints and prior
      knowledge about a certain language in the recognition procedure. Experiments on
      two standard benchmarks, Dataset-CASIA and Dataset-ICDAR, yielded outstanding
      results, with correct rates of 97.50 and 96.58 percent, respectively, which are
      significantly better than the best result reported thus far in the literature.

PMID- 28767365
TI  - A Novel Method for Low-Contrast and High-Noise Vessel Segmentation and Location
      in Venipuncture.
AB  - Blood sampling is the most common medical technique, and vessel detection is of
      crucial interest for automated venipuncture systems. In this paper, we propose a
      new convex-regional-based gradient model that uses contextually related regional
      information, including vessel width size and gray distribution, to segment and
      locate vessels in a near-infrared image. A convex function with the interval size
      of vessel width is constructed and utilized for its edge-preserving superiority.
      Moreover, white and linear noise independences are derived. The region-based
      gradient decreases the number of local extreme in the cross-sectional profile of
      the vessel to realize its single global minimum in a low-contrast, noisy image.
      We demonstrate the performance of the proposed model via quantitative tests and
      comparisons between different methods. Results show the advantages of the model
      on the continuity and smoothness of segmented vessel. The proposed model is
      evaluated with receiver operating characteristic curves, which have a
      corresponding area under the curve of 88.8%. The proposed model will be a
      powerful method in automated venipuncture system and medical image analysis.

PMID- 28767367
TI  - 3-D In Vitro Acoustic Super-Resolution and Super-Resolved Velocity Mapping Using
      Microbubbles.
AB  - Standard clinical ultrasound (US) imaging frequencies are unable to resolve
      microvascular structures due to the fundamental diffraction limit of US waves.
      Recent demonstrations of 2-D super-resolution both in vitro and in vivo have
      demonstrated that fine vascular structures can be visualized using acoustic
      single bubble localization. Visualization of more complex and disordered 3-D
      vasculature, such as that of a tumor, requires an acquisition strategy which can
      additionally localize bubbles in the elevational plane with high precision in
      order to generate super-resolution in all three dimensions. Furthermore, a
      particular challenge lies in the need to provide this level of visualization with
      minimal acquisition time. In this paper, we develop a fast, coherent US imaging
      tool for microbubble localization in 3-D using a pair of US transducers
      positioned at 90 degrees . This allowed detection of point scatterer signals in 3
      D with average precisions equal to [Formula: see text] in axial and elevational
      planes, and [Formula: see text] in the lateral plane, compared to the diffraction
      limited point spread function full-widths at half-maximum of 488, 1188, and
      [Formula: see text] of the original imaging system with a single transducer.
      Visualization and velocity mapping of 3-D in vitro structures was demonstrated
      far beyond the diffraction limit. The capability to measure the complete flow
      pattern of blood vessels associated with disease at depth would ultimately enable
      analysis of in vivo microvascular morphology, blood flow dynamics, and occlusions
      resulting from disease states.

PMID- 28767366
TI  - Detector Blur and Correlated Noise Modeling for Digital Breast Tomosynthesis
      Reconstruction.
AB  - This paper describes a new image reconstruction method for digital breast
      tomosynthesis (DBT). The new method incorporates detector blur into the forward
      model. The detector blur in DBT causes correlation in the measurement noise. By
      making a few approximations that are reasonable for breast imaging, we formulated
      a regularized quadratic optimization problem with a data-fit term that
      incorporates models for detector blur and correlated noise (DBCN). We derived a
      computationally efficient separable quadratic surrogate (SQS) algorithm to solve
      the optimization problem that has a non-diagonal noise covariance matrix. We
      evaluated the SQS-DBCN method by reconstructing DBT scans of breast phantoms and
      human subjects. The contrast-to-noise ratio and sharpness of microcalcifications
      were analyzed and compared with those by the simultaneous algebraic
      reconstruction technique. The quality of soft tissue lesions and parenchymal
      patterns was examined. The results demonstrate the potential to improve the image
      quality of reconstructed DBT images by incorporating the system physics model.
      This paper is a first step toward model-based iterative reconstruction for DBT.

PMID- 28767368
TI  - Model-Based Referenceless Quality Metric of 3D Synthesized Images Using Local
      Image Description.
AB  - New challenges have been brought out along with the emerging of 3D-related
      technologies, such as virtual reality, augmented reality (AR), and mixed reality.
      Free viewpoint video (FVV), due to its applications in remote surveillance,
      remote education, and so on, based on the flexible selection of direction and
      viewpoint, has been perceived as the development direction of next-generation
      video technologies and has drawn a wide range of researchers' attention. Since
      FVV images are synthesized via a depth image-based rendering (DIBR) procedure in
      the "blind" environment (without reference images), a reliable real-time blind
      quality evaluation and monitoring system is urgently required. But existing
      assessment metrics do not render human judgments faithfully mainly because
      geometric distortions are generated by DIBR. To this end, this paper proposes a
      novel referenceless quality metric of DIBR-synthesized images using the
      autoregression (AR)-based local image description. It was found that, after the
      AR prediction, the reconstructed error between a DIBR-synthesized image and its
      AR-predicted image can accurately capture the geometry distortion. The visual
      saliency is then leveraged to modify the proposed blind quality metric to a
      sizable margin. Experiments validate the superiority of our no-reference quality
      method as compared with prevailing full-, reduced-, and no-reference models.

PMID- 28767369
TI  - Extending Correlation Filter-Based Visual Tracking by Tree-Structured Ensemble
      and Spatial Windowing.
AB  - Correlation filters have been successfully used in visual tracking due to their
      modeling power and computational efficiency. However, the state-of-the-art
      correlation filter-based (CFB) tracking algorithms tend to quickly discard the
      previous poses of the target, since they consider only a single filter in their
      models. On the contrary, our approach is to register multiple CFB trackers for
      previous poses and exploit the registered knowledge when an appearance change
      occurs. To this end, we propose a novel tracking algorithm [of complexity O(D) ]
      based on a large ensemble of CFB trackers. The ensemble [of size O(2D) ] is
      organized over a binary tree (depth D ), and learns the target appearance
      subspaces such that each constituent tracker becomes an expert of a certain
      appearance. During tracking, the proposed algorithm combines only the appearance
      aware relevant experts to produce boosted tracking decisions. Additionally, we
      propose a versatile spatial windowing technique to enhance the individual expert
      trackers. For this purpose, spatial windows are learned for target objects as
      well as the correlation filters and then the windowed regions are processed for
      more robust correlations. In our extensive experiments on benchmark datasets, we
      achieve a substantial performance increase by using the proposed tracking
      algorithm together with the spatial windowing.

PMID- 28767370
TI  - LLE Score: A New Filter-Based Unsupervised Feature Selection Method Based on
      Nonlinear Manifold Embedding and Its Application to Image Recognition.
AB  - The task of feature selection is to find the most representative features from
      the original high-dimensional data. Because of the absence of the information of
      class labels, selecting the appropriate features in unsupervised learning
      scenarios is much harder than that in supervised scenarios. In this paper, we
      investigate the potential of locally linear embedding (LLE), which is a popular
      manifold learning method, in feature selection task. It is straightforward to
      apply the idea of LLE to the graph-preserving feature selection framework.
      However, we find that this straightforward application suffers from some
      problems. For example, it fails when the elements in the feature are all equal;
      it does not enjoy the property of scaling invariance and cannot capture the
      change of the graph efficiently. To solve these problems, we propose a new filter
      based feature selection method based on LLE in this paper, which is named as LLE
      score. The proposed criterion measures the difference between the local structure
      of each feature and that of the original data. Our experiments of classification
      task on two face image data sets, an object image data set, and a handwriting
      digits data set show that LLE score outperforms state-of-the-art methods,
      including data variance, Laplacian score, and sparsity score.

PMID- 28767371
TI  - Category-Specific Object Image Denoising.
AB  - We present a novel image denoising algorithm that uses external, category
      specific image database. In contrast to existing noisy image restoration
      algorithms that search patches either from a generic database or noisy image
      itself, our method first selects clean images similar to the noisy image from a
      database that consists of images of the same class. Then, within the spatial
      locality of each noisy patch, it assembles a set of "support patches" from the
      selected images. These noisy-free support samples resemble the noisy patch and
      correspond principally to the identical part of the depicted object. In addition,
      we employ a content adaptive distribution model for each patch, where we derive
      the parameters of the distribution from the support patches. We formulate noise
      removal task as an optimization problem in the transform domain. Our objective
      function composed of a Gaussian fidelity term that imposes category specific
      information, and a low-rank term that encourages the similarity between the noisy
      and the support patches in a robust manner. The denoising process is driven by an
      iterative selection of support patches and optimization of the objective
      function. Our extensive experiments on five different object categories confirm
      the benefit of incorporating category-specific information to noise removal and
      demonstrate the superior performance of our method over the state-of-the-art
      alternatives.

PMID- 28767372
TI  - Texture Classification and Visualization of Time Series of Gait Dynamics in
      Patients With Neuro-Degenerative Diseases.
AB  - The analysis of gait dynamics is helpful for predicting and improving the quality
      of life, morbidity, and mortality in neuro-degenerative patients. Feature
      extraction of physiological time series and classification between gait patterns
      of healthy control subjects and patients are usually carried out on the basis of
      1-D signal analysis. The proposed approach presented in this paper departs itself
      from conventional methods for gait analysis by transforming time series into
      images, of which texture features can be extracted from methods of texture
      analysis. Here, the fuzzy recurrence plot algorithm is applied to transform gait
      time series into texture images, which can be visualized to gain insight into
      disease patterns. Several texture features are then extracted from fuzzy
      recurrence plots using the gray-level co-occurrence matrix for pattern analysis
      and machine classification to differentiate healthy control subjects from
      patients with Parkinson's disease, Huntington's disease, and amyotrophic lateral
      sclerosis. Experimental results using only the right stride-intervals of the four
      groups show the effectiveness of the application of the proposed approach.

PMID- 28767373
TI  - Mixed Neural Network Approach for Temporal Sleep Stage Classification.
AB  - This paper proposes a practical approach to addressing limitations posed by using
      of single-channel electroencephalography (EEG) for sleep stage classification.
      EEG-based characterizations of sleep stage progression contribute the diagnosis
      and monitoring of the many pathologies of sleep. Several prior reports explored
      ways of automating the analysis of sleep EEG and of reducing the complexity of
      the data needed for reliable discrimination of sleep stages at lower cost in the
      home. However, these reports have involved recordings from electrodes placed on
      the cranial vertex or occiput, which are both uncomfortable and difficult to
      position. Previous studies of sleep stage scoring that used only frontal
      electrodes with a hierarchical decision tree motivated this paper, in which we
      have taken advantage of rectifier neural network for detecting hierarchical
      features and long short-term memory network for sequential data learning to
      optimize classification performance with single-channel recordings. After
      exploring alternative electrode placements, we found a comfortable configuration
      of a single-channel EEG on the forehead and have shown that it can be integrated
      with additional electrodes for simultaneous recording of the electro-oculogram.
      Evaluation of data from 62 people (with 494 hours sleep) demonstrated better
      performance of our analytical algorithm than is available from existing
      approaches with vertex or occipital electrode placements. Use of this recording
      configuration with neural network deconvolution promises to make clinically
      indicated home sleep studies practical.

PMID- 28767374
TI  - Continuous Petri Nets and microRNA Analysis in Melanoma.
AB  - Personalized target therapies represent one of the possible treatment strategies
      to fight the ongoing battle against cancer. New treatment interventions are still
      needed for an effective and successful cancer therapy. In this scenario, we
      simulated and analyzed the dynamics of BRAF V600E melanoma patients treated with
      BRAF inhibitors in order to find potentially interesting targets that may make
      standard treatments more effective in particularly aggressive tumors that may not
      respond to selective inhibitor drugs. To this aim, we developed a continuous
      Petri Net model that simulates fundamental signalling cascades involved in
      melanoma development, such as MAPK and PI3K/AKT, in order to deeply analyze these
      complex kinase cascades and predict new crucial nodes involved in
      melanomagenesis. The model pointed out that some microRNAs, like hsa-mir-132,
      downregulates expression levels of p120RasGAP: under high concentrations of
      p120RasGAP, MAPK pathway activation is significantly decreased and consequently
      also PI3K/PDK1/AKT activation. Furthermore, our analysis carried out through the
      Genomic Data Commons (GDC) Data Portal shows the evidence that hsa-mir-132 is
      significantly associated with clinical outcome in melanoma cancer genomic data
      sets of BRAF-mutated patients. In conclusion, targeting miRNAs through antisense
      oligonucleotides technology may suggest the way to enhance the action of BRAF
      inhibitors.

PMID- 28767375
TI  - A Trust Model for Ubiquitous Healthcare Environment on the Basis of Adaptable
      Fuzzy-Probabilistic Inference System.
AB  - Trust is considered to be a determinant on psychologist selection which can
      ensure patient satisfaction. Hence, trust concept is essential to be introduced
      into ubiquitous healthcare (UH) environment oriented on patients with anxiety
      disorders. This is accomplished by trust model estimating psychologists'
      trustworthiness, a priory to service delivery, with the use of patient's and
      his/her acquaintances testimonies, i.e., personal interaction experience and
      reputation (R). In this paper, a trust model is proposed to be materialized via
      an adaptable cloud inference system (ACIS) that performs trust value (TV)
      estimation. Taking advantage of a cloud theory, the introduced ACIS estimates TVs
      via fuzzy-probabilistic reasoning incorporating a cloud relation operator (soft
      AND) which is proposed to be tuned by trust information sources consistency and
      coherency. Theoretical analysis along with comparative study conducted within
      MATLAB environment and experimental investigation verify the effectiveness of the
      proposed ACIS materialization under different conditions. Especially, the
      innovative features of ACIS enable TV to be estimated with 45.5% and 62% on
      average higher accuracy to that providing state-of-the-art trust models, within
      clean environment and under the influence of large-scale collusive malicious
      attacks, respectively. The enhanced robustness permits the untrustworthy UH
      providers to be discriminated with true positive rate at the range of 0.9
      although 40% of R testimonies are erroneous. Finally, experimental investigation
      validates that the adoption of the proposed trust model for psychologists
      trustworthiness estimation facilitates patient satisfaction to be achieved into
      UH environment.

PMID- 28767376
TI  - EHDC: An Energy Harvesting Modeling and Profiling Platform for Body Sensor
      Networks.
AB  - Energy harvesting is a promising solution to the limited battery lifetimes of
      body sensor nodes. Self-powered sensor systems capable of quasi-perpetual
      operation enable the possibility of truly continuous monitoring of patients
      beyond the clinic. However, the discontinuous and dynamic characteristics of
      harvesting in real-world scenarios-and their implications for the design and
      operation of self-powered systems-are not yet well understood. This paper
      presents a mobile energy harvesting and data collection (EHDC) platform designed
      to provide a deeper understanding of energy harvesting dynamics. The EHDC
      platform monitors and records the instantaneous usable power generated by body
      worn harvesters, while also collecting human activity and environmental data to
      provide a comprehensive real-world evaluation of two energy harvesting modalities
      common to body sensor networks: solar and thermoelectric. The platform was
      initially validated with benchtop tests and later with real-world deployments on
      two subjects. 7-h-long multimodal energy harvesting profiles were generated, and
      the environmental and behavioral data were used to expand upon previously
      developed Kalman filter based mathematical models for energy harvesting
      prediction. Results confirm the validity of the EHDC platform and harvesting
      models, establishing the potential for longer term monitoring of energy
      harvesting characteristics; thus, informing the design and operation of self
      powered body sensor networks.

PMID- 28767377
TI  - Denoising Hyperspectral Image With Non-i.i.d. Noise Structure.
AB  - Hyperspectral image (HSI) denoising has been attracting much research attention
      in remote sensing area due to its importance in improving the HSI qualities. The
      existing HSI denoising methods mainly focus on specific spectral and spatial
      prior knowledge in HSIs, and share a common underlying assumption that the
      embedded noise in HSI is independent and identically distributed (i.i.d.). In
      real scenarios, however, the noise existed in a natural HSI is always with much
      more complicated non-i.i.d. statistical structures and the under-estimation to
      this noise complexity often tends to evidently degenerate the robustness of
      current methods. To alleviate this issue, this paper attempts the first effort to
      model the HSI noise using a non-i.i.d. mixture of Gaussians (NMoGs) noise
      assumption, which finely accords with the noise characteristics possessed by a
      natural HSI and thus is capable of adapting various practical noise shapes. Then
      we integrate such noise modeling strategy into the low-rank matrix factorization
      (LRMF) model and propose an NMoG-LRMF model in the Bayesian framework. A
      variational Bayes algorithm is then designed to infer the posterior of the
      proposed model. As substantiated by our experiments implemented on synthetic and
      real noisy HSIs, the proposed method performs more robust beyond the state-of-the
      arts.

PMID- 28767378
TI  - Adaptive Neural Network Control of a Robotic Manipulator With Time-Varying Output
      Constraints.
AB  - The control problem of an uncertain n -degrees of freedom robotic manipulator
      subjected to time-varying output constraints is investigated in this paper. We
      describe the rigid robotic manipulator system as a multi-input and multi-output
      nonlinear system. We devise a disturbance observer to estimate the unknown
      disturbance from humans and environment. To solve the uncertain problem, a neural
      network which utilizes a radial basis function is used to estimate the unknown
      dynamics of the robotic manipulator. An asymmetric barrier Lyapunov function is
      employed in the process of control design to avert the contravention of the time
      varying output constraints. Simulation results validate the validity of the
      presented control scheme.

PMID- 28767379
TI  - Composite Backstepping Consensus Algorithms of Leader-Follower Higher-Order
      Nonlinear Multiagent Systems Subject to Mismatched Disturbances.
AB  - This paper is devoted to solving the output consensus problem of leader-follower
      higher-order nonlinear multiagent systems subject to mismatched disturbances. The
      disturbances are allowed to be in higher-order forms. First, by constructing a
      generalized proportional-integral observer for each follower, estimates of the
      disturbances and their derivatives are obtained. At the same time, a distributed
      observer is also developed for the followers to estimate the leader state
      information. Second, based on the estimates of the disturbances and the leader
      state, together with the backstepping technique, a feedforward-feedback composite
      consensus control scheme is proposed. The designed distributed protocols
      guarantee asymptotic output consensus for the agents. Simulation results validate
      the effectiveness of the proposed composite control scheme.

PMID- 28767380
TI  - Delay-Dependent Functional Observer Design for Linear Systems With Unknown Time
      Varying State Delays.
AB  - Partial state estimation has numerous applications in practice. Nevertheless,
      designing delay-dependent functional observers (FOs) for systems with unknown
      time delays is rigorous and still an open dilemma. This paper addresses the
      problem for linear time-invariant systems with state time-varying delays. The
      delay is assumed to be bounded in an interval with a bounded derivative. A
      sliding mode FO structure that is robust against the delay uncertainties is
      established to this aim. The structure employs an auxiliary delay function that
      can be defined based on the existing knowledge on the actual delay values. Delay
      dependent sufficient conditions for the stability of the observer are obtained
      using the Lyapunov Krasovskii approach, and are expressed in terms of a linear
      matrix inequality and two rank conditions. The delay-free observer structure is
      additionally studied and the necessary and sufficient conditions for its
      stability are obtained. Two descriptive numerical examples and simulation results
      demonstrate the design procedure and emphasize the effectiveness of the proposed
      observer design algorithm.

PMID- 28767381
TI  - Towards Occlusion Handling: Object Tracking With Background Estimation.
AB  - The appearance model of the target needs to be updated for online single object
      tracking. However, the variation of the observation can be caused by active
      appearance change of the target, or the occlusion from the background. For the
      former case, we should update the appearance model and for the latter, the
      current model should be preserved. In this paper, we distinguish these two cases
      and resist the impact from heavy occlusion by estimating the background in the
      scene with moving cameras, while retaining the adaptivity to stationary cameras
      at the same time. The proposed method formulates the background as a Gaussian
      model and the target is determined in a coarse-to-fine manner. Experimental
      results demonstrate that our method achieves competitive results in the sequences
      with appearance changes and outperforms the state-of-the-art algorithms in
      dealing with complex occlusions.

PMID- 28767382
TI  - Output Feedback Control and Stabilization for Multiplicative Noise Systems With
      Intermittent Observations.
AB  - This paper mainly focuses on the optimal output feedback control and
      stabilization problems for discrete-time multiplicative noise system with
      intermittent observations. The main contributions of this paper can be concluded
      as follows. First, different from the previous literatures, this paper overcomes
      the barrier of the celebrated separation principle for stochastic control
      problems of multiplicative noise systems. Based on the measurement process, the
      optimal estimation is presented, and by using dynamic programming principle, the
      optimal output feedback controller is designed with feedback gain based on the
      given coupled Riccati equations. Second, the necessary and sufficient
      stabilization conditions for multiplicative noise system with intermittent
      observation in the mean square sense are developed for the first time. Finally,
      the novel results developed in this paper can be applied to solve the output
      feedback control and stabilization problems for general networked control system
      of user datagram protocol network case. The range of packet losses rate and the
      allowable maximum packet losses rate are presented explicitly.

PMID- 28767383
TI  - Privacy Preservation in Distributed Subgradient Optimization Algorithms.
AB  - In this paper, some privacy-preserving features for distributed subgradient
      optimization algorithms are considered. Most of the existing distributed
      algorithms focus mainly on the algorithm design and convergence analysis, but not
      the protection of agents' privacy. Privacy is becoming an increasingly important
      issue in applications involving sensitive information. In this paper, we first
      show that the distributed subgradient synchronous homogeneous-stepsize algorithm
      is not privacy preserving in the sense that the malicious agent can
      asymptotically discover other agents' subgradients by transmitting untrue
      estimates to its neighbors. Then a distributed subgradient asynchronous
      heterogeneous-stepsize projection algorithm is proposed and accordingly its
      convergence and optimality is established. In contrast to the synchronous
      homogeneous-stepsize algorithm, in the new algorithm agents make their
      optimization updates asynchronously with heterogeneous stepsizes. The introduced
      two mechanisms of projection operation and asynchronous heterogeneous-stepsize
      optimization can guarantee that agents' privacy can be effectively protected.

PMID- 28767384
TI  - Distributed Differential Evolution Based on Adaptive Mergence and Split for Large
      Scale Optimization.
AB  - Nowadays, large-scale optimization problems are ubiquitous in many research
      fields. To deal with such problems efficiently, this paper proposes a distributed
      differential evolution with adaptive mergence and split (DDE-AMS) on
      subpopulations. The novel mergence and split operators are designed to make full
      use of limited population resource, which is important for large-scale
      optimization. They are adaptively performed based on the performance of the
      subpopulations. During the evolution, once a subpopulation finds a promising
      region, the current worst performing subpopulation will merge into it. If the
      merged subpopulation could not continuously provide competitive solutions, it
      will be split in half. In this way, the number of subpopulations is adaptively
      adjusted and better performing subpopulations obtain more individuals. Thus,
      population resource can be adaptively arranged for subpopulations during the
      evolution. Moreover, the proposed algorithm is implemented with a parallel master
      slave manner. Extensive experiments are conducted on 20 widely used large-scale
      benchmark functions. Experimental results demonstrate that the proposed DDE-AMS
      could achieve competitive or even better performance compared with several state
      of-the-art algorithms. The effects of DDE-AMS components, adaptive behavior,
      scalability, and parameter sensitivity are also studied. Finally, we investigate
      the speedup ratios of DDE-AMS with different computation resources.

PMID- 28767385
TI  - Left anterior descending coronary artery dissection during ventricular
      tachycardia ablation - case report.
AB  - Fascicular left ventricular tachycardia (VT) is the second most frequent
      idiopathic left VT in the setting of a structurally normal heart. Catheter
      ablation is curative in most patients with low complication rates. We report a
      case of ostial left anterior descending coronary artery (LAD) occlusion during
      fascicular ventricular tachycardia ablation. Dissection was the most likely cause
      of LAD obstruction. To the authors' best knowledge, this is the first case
      reporting selective LAD dissection during electrophysiology study with no left
      main coronary artery (LMCA) affection.

PMID- 28767452
TI  - Ultra-small v-shaped gold split ring resonators for biosensing using fundamental
      magnetic resonance in the visible spectrum.
AB  - Strong light localization within metal nanostructures occurs by collective
      oscillations of plasmons in the form of electric and magnetic resonances. This so
      called localized surface plasmon resonance (LSPR) has gained much interest in the
      development of low-cost sensing platforms in the visible spectrum. However,
      demonstrations of LSPR-based sensing are mostly limited to electric resonances
      due to the technological limitations for achieving magnetic resonances in the
      visible spectrum. In this work, we report the first demonstration of LSPR sensing
      based on fundamental magnetic resonance in the visible spectrum using ultrasmall
      gold v-shaped split ring resonators. Specifically, we show the ability for
      detecting adsorption of bovine serum albumin and cytochrome c biomolecules at
      monolayer levels, and the selective binding of protein A/G to immunoglobulin G.

PMID- 28767453
TI  - Ultrasonographic Assessment of Bladder Volumes in Children Undergoing Penile
      Surgery: Does the Type of Anesthesia Matter?
AB  - BACKGROUND: There are scant data reporting postoperative ultrasonographically
      measured bladder volumes in children undergoing penile surgery. STUDY QUESTION:
      We studied the effect of various anesthesia techniques on return of micturition
      after penile surgery in children, using ultrasonographically measured bladder
      volumes. DATA SOURCES: Ultrasonographically measured postvoiding residual bladder
      volumes indexed to age-appropriate capacity, and time elapsed between the end of
      surgery and spontaneous voiding after pediatric circumcision, distal hypospadias
      repair, or repair of urethrocutaneous fistula, were studied. STUDY DESIGN:
      Children between 4 months and 12 years were randomized to caudal block,
      intravenous (IV) fentanyl or penile block, in association with inhaled general
      anesthesia. Bladder volumes were measured before surgery and immediately after
      voiding for the first time. Time to first postsurgery void was also recorded.
      RESULTS: Thirty-one children completed all assessments; 12 underwent caudal
      block, 9 IV fentanyl anesthesia, and 7 were given penile block. The mean first
      postvoid bladder residual volumes were highest in the caudal and lowest in the
      penile block children (27.5 vs. 17.3 mL, P = 0.003). The time elapsing between
      the end of surgery and first voiding was the longest in the fentanyl group
      compared with caudal and penile blocks (232, 178, 150 minutes, respectively, P =
      0.02). CONCLUSIONS: None of the anesthetic techniques provoked postoperative
      urinary retention after minor penile surgery in children. The penile block
      appears superior to caudal block or to IV fentanyl-based anesthesia with regard
      to postoperative recovery of normal micturition.

PMID- 28767454
TI  - Acneiform Rash With Ramucirumab and Paclitaxel in a Patient With Recurrent
      Esophageal Cancer.

PMID- 28767455
TI  - Minocycline-Associated Pancreatitis.

PMID- 28767457
TI  - Comment on "Comparison of Anterior Segment Optical Coherence Tomography Bleb
      Grading, Moorfields Bleb Grading System, and Intraocular Pressure After
      Trabeculectomy".

PMID- 28767456
TI  - Effects of anaesthesia and analgesia on long-term outcome after total knee
      replacement: A prospective, observational, multicentre study.
AB  - BACKGROUND: Perioperative regional anaesthesia may protect from persistent
      postsurgical pain (PPSP) and improve outcome after total knee arthroplasty (TKA).
      OBJECTIVES: Aim of this study was to evaluate the impact of regional anaesthesia
      on PPSP and long-term functional outcome after TKA. DESIGN: A web-based
      prospective observational registry. SETTING: Five Italian Private and University
      Hospitals from 2012 to 2015. PATIENTS: Undergoing primary unilateral TKA, aged
      more than 18 years, informed consent, American Society of Anesthesiologists (ASA)
      physical status classes 1 to 3, no previous knee surgery. INTERVENTION(S):
      Personal data (age, sex, BMI and ASA class), preoperative pain assessed by
      numerical rating scale (NRS) score, and risk factors for PPSP were registered
      preoperatively. Data on anaesthetic and analgesic techniques were collected.
      Postoperative pain (NRS), analgesic consumption, major complications and patient
      satisfaction were registered up to the time of discharge. PPSP was assessed by a
      blinded investigator during a phone call after 1, 3 and 6 months, together with
      patient satisfaction, quality of life (QOL) and walking ability. MAIN OUTCOME
      MEASURES: Experience of PPSP according to the type of peri-operative analgesia.
      RESULTS: Five hundred sixty-three patients completed the follow-up. At 6 months,
      21.6% of patients experienced PPSP, whereas autonomy was improved only in 56.3%;
      QOL was worsened or unchanged in 30.7% of patients and improved in 69.3%.
      Patients receiving continuous regional anaesthesia (epidural or peripheral nerve
      block) showed a lower NRS through the whole peri-operative period up to 1 month
      compared with both single shot peripheral nerve block and those who did not
      receive any type of regional anaesthesia. No difference was found between these
      latter two groups. Differences in PPSP at 3 or 6 months were not significantly
      affected by the type of anaesthesia or postoperative analgesia. A higher NRS
      score at 1 month, younger age, history of anxiety or depression, pro-inflammatory
      status, higher BMI and a lower ASA physical status were associated with a higher
      incidence of PPSP and worsened QOL at 6 months. CONCLUSION: Continuous regional
      anaesthesia provides analgesic benefit for up to 1 month after surgery, but did
      not influence PPSP at 6 months. Better pain control at 1 month was associated
      with reduced PPSP. Patients with higher expectations from surgery, enhanced basal
      inflammation and a pessimistic outlook are more prone to develop PPSP. TRIAL
      REGISTRATION: Clinicaltrials.gov identifier: NCT02147730.

PMID- 28767458
TI  - Medium-term Outcomes of Unsutured Scleral Flap Trabeculectomies: Comment.

PMID- 28767459
TI  - Bleb Grading Using Anterior Segment Optical Coherence Tomography.

PMID- 28767460
TI  - Optic Nerve Head Drusen: Imaging Using Optical Coherence Tomography Angiography.
AB  - PURPOSE: To describe findings and utility of optical coherence tomography
      angiography (OCTA) in optic nerve head drusen (ONHD). OBSERVATIONS: A 57-year-old
      white man presented with a decrease in contrast sensitivity of the inferior
      visual field in both eyes. Clinical examination, visual fields, optical coherence
      tomography, fundus autofluorescence and OCTA revealed ONHD bilaterally. A focal
      decrease in vessel density within the localization of ONHD in both eyes was
      demonstrated suggesting a connection between those findings. CONCLUSIONS AND
      IMPORTANCE: This is the first report in which peripapillary vessel density is
      analyzed using OCTA technology for this entity. OCTA could confirm the diagnosis
      and has the potential to assist with the diagnosis and evaluation of progression
      of ONHD.

PMID- 28767461
TI  - Long-term Outcome of Argon Laser Peripheral Iridoplasty in the Management of
      Plateau Iris Syndrome Eyes.
AB  - PURPOSE: To report long-term (>5 y) outcomes of plateau iris syndrome patients
      treated with argon laser peripheral iridoplasty (ALPI). PATIENTS AND METHODS: A
      retrospective chart review was performed on all patients with plateau iris
      syndrome treated with ALPI from 1996 to 2007. The study included 22 eyes from 22
      patients with plateau iris after peripheral iridotomy that were followed for at
      least 1 year after ALPI. The primary outcome was incidence of needing any
      intraocular pressure (IOP)-lowering medications or surgery (either a filtering
      procedure or phacoemulsification). Demographic and baseline clinical data were
      summarized by mean (+/-SD) or frequency (percentage). Snellen best-corrected
      visual acuity was converted to logMAR. The paired t test was used to compare IOP
      changes, number of IOP-lowering medications, and best-corrected visual acuity
      from baseline to annual follow-up. RESULTS: Mean follow-up was 76 months. Only 2
      (9%) eyes maintained an IOP<21 mm Hg without requiring medication or surgery.
      Seventeen (77%) eyes underwent surgery at an average of 49.1+/-7.9 months after
      ALPI. Eight (36%) eyes underwent filtering surgery, and 9 (41%) eyes underwent
      phacoemulsification. Three months after cataract extraction, no eyes required IOP
      lowering medication. CONCLUSIONS: The beneficial effects of ALPI last for <4
      years, with the majority of patients (77%) requiring surgery. Phacoemulsification
      alone was a successful treatment for plateau iris in our patient population.

PMID- 28767462
TI  - Efficacy and Safety of Simeprevir or Daclatasvir in Combination With Sofosbuvir
      for the Treatment of Hepatitis C Genotype 4 Infection.
AB  - INTRODUCTION: The combination of sofosbuvir (SOF) with simeprevir (SMV) or
      daclatasvir (DCV) is very effective in treating hepatitis C virus (HCV)
      infection, particularly genotype (GT) 1. However, the data on GT4 are very
      limited. We aimed to determine the efficacy and safety of SOF in combination with
      either SMV or DCV in GT4-infected patients. PATIENTS AND METHODS: In this real
      life, prospective, observational study, HCV (GT4) patients (n=96) were evaluated
      in 2 groups on the basis of the 12-week treatment regimen they received. Group 1
      (n=56) patients were treated with SOF and SMV+/-ribavirin (RBV), whereas group 2
      patients were treated with SOF and DCV+/-RBV (n=40). The primary efficacy
      endpoint was sustained virologic response 12, whereas the primary safety endpoint
      was drug discontinuation or occurrence of grade 3/4 adverse events. RESULTS: The
      mean age was 49+/-14.6 years (59.4% men). Cirrhosis was present in 53.6% and
      35.0% of groups 1 and 2, respectively, whereas 27 patients (48.2%) in group 1 and
      21 patients (52.5%) in group 2 had failed prior interferon-based treatment. The
      median pretreatment HCV-RNA log10 was 6.1 (3.6 to 7.0) and 6.0 (3.6 to 7.2) IU/mL
      in groups 1 and 2, respectively. RBV was given to 17 patients (30.4%) in group 1
      and 2 patients (5%) in group 2. All patients achieved sustained virologic
      response 12 (100%). Adverse events occurred in 32% of patients (grade 1 and 2),
      but none discontinued treatment. One patient died in the SMV group (not related
      to treatment). CONCLUSIONS: SMV/SOF or DCV/SOF combinations are safe and highly
      effective in HCV-GT4 treatment. Cirrhosis and failure of prior interferon-based
      treatment did not influence treatment response.

PMID- 28767463
TI  - Can the Sum of Adenoma Diameters (Adenoma Bulk) on Index Examination Predict Risk
      of Metachronous Advanced Neoplasia?
AB  - BACKGROUND: Recent data suggest that adenoma size and number are more important
      predictors of metachronous colorectal neoplasia than advanced histology.
      Furthermore, there is poor reproducibility in diagnosing advanced histology; high
      grade dysplasia and villous histology. Therefore we developed a new metric,
      adenoma bulk, the sum of diameters of all baseline adenomas, regardless of
      advanced features. GOAL: Compare the predictive value for metachronous advanced
      neoplasia of adenoma bulk to conventional paradigm. STUDY: Data were collected
      prospectively in a multicenter adenoma-chemoprevention trial (2004 to 2013). For
      the conventional paradigm, high-risk baseline findings were defined as >=3
      adenomas, large adenomas (>=1 cm) or adenomas with villous components or high
      grade dysplasia. Adenoma bulk was examined across quartiles and as a continuous
      variable. Predictive characteristics (sensitivities, specificities, c-statistics)
      for metachronous advanced neoplasia using conventional criteria and adenoma bulk
      were calculated. receiver operator characteristic curves were computed using
      logistic regression. RESULTS: In total, 1948 adults had index and follow-up
      colonoscopies (mean follow-up, 45.2 mo). Those with an adenoma bulk >=10 mm (4th
      quartile) had a higher metachronous advanced neoplasia risk (14.4% vs. 6.9-8.2%
      in lower 3 quartiles; P=0.0002). The c-statistics and sensitivities (specificity
      fixed at 0.73) for the adenoma bulk and conventional models were 0.587 and 0.563
      (P=0.17) and 0.396 and 0.390, respectively. CONCLUSIONS: Categorizing sporadic
      adenoma patients as high versus low risk for metachronous advanced neoplasia by
      adenoma bulk of <versus >=10 mm may be comparably predictive as conventional
      paradigm and simplifies risk stratification by obviating need for additional
      histology regarding extent of villous component or degree of dysplasia in
      resected polyps. The adenoma bulk metric and the 10 mm cutoff in particular would
      have to be validated in other populations before it can be used in clinical
      practice.

PMID- 28767464
TI  - Role of Osteogenic Coatings on Implant Surfaces in Promoting Bone-To-Implant
      Contact in Experimental Osteoporosis: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate
      the role of osteogenic coatings (placement of a thin film of organic and
      inorganic osteoinductive and osteoproliferative materials) on implant surfaces in
      augmenting bone-to-implant contact (BIC) in osteoporotic bone. DATA SOURCES: To
      answer the focused question "Do osteogenic coatings on implant surfaces increase
      BIC in osteoporotic bone?" PubMed/MEDLINE, EMBASE, ISI Web of Knowledge, Scopus,
      and Google-Scholar databases were searched till June 2017 using different
      combinations of the following key words: bone-to-implant contact, coating,
      implant surface, osseointegration, and osteoporosis. Letters to the Editor,
      review articles, case-reports/case-series, and commentaries were excluded.
      RESULTS: Six animal studies were included, in which osteoporosis was induced by
      bilateral ovariectomy. In all studies, implant surface roughness was increased by
      various osteogenic surface coatings including alumina, hydroxyapatite, calcium
      phosphate, and zoledronic acid. Five studies showed that bone volume and BIC are
      significantly higher around implants with coated surfaces than noncoated
      implants. In 1 study, there was no difference in BIC around coated and noncoated
      implants. CONCLUSION: Although experimental studies have shown that osteogenic
      coatings are effective in enhancing BIC, their clinical relevance requires
      further investigations.

PMID- 28767466
TI  - The Care Team Visit: Approaching Interdisciplinary Rounds With Renewed Focus.
AB  - Interdisciplinary bedside rounds serve as a key mechanism to coordinate patient
      centered care. With a focus on optimizing rounds, an interdisciplinary team
      developed an enhanced, structured process, coined the care team visit. Key
      findings included improved nurse participation, increased staff collaboration,
      and decreased Foley catheter days. The process outlined can be used by health
      care professionals to improve the effectiveness of interdisciplinary bedside
      rounds.

PMID- 28767467
TI  - Innovative Approach to Reconstruct Bedside Handoff: Using Simple Rules of
      Complexity Science to Promote Partnership With Patients.
AB  - When nurses integrate patient expertise, nurse-to-nurse handoff becomes patient
      centered (nurse and patient), and the weak link between quality and safety is
      mitigated. The existing paradigm for handoff is an ineffective measure to
      minimize errors. This article describes a reimagined bedside handoff
      transitioning handoff from its prescriptive nurse-centered interaction to a
      patient-centered partnership using the principles of complex adaptive systems,
      simple rules, and partnerships that address the uniqueness of each patient and
      nurse interaction.

PMID- 28767468
TI  - Improving Patient Care Outcomes Through Better Delegation-Communication Between
      Nurses and Assistive Personnel.
AB  - In acute care settings, registered nurses need to delegate effectively to
      unlicensed assistive personnel to provide safe care. This project explored the
      impact of improved delegation-communication between nurses and unlicensed
      assistive personnel on pressure injury rates, falls, patient satisfaction, and
      delegation practices. Findings revealed a tendency for nurses to delay the
      decision to delegate. However, nurses' ability to explain performance appraisals,
      facilitate clearer communication, and seek feedback improved. Patient outcomes
      revealed decreased falls and improved patient satisfaction.

PMID- 28767469
TI  - Marijuana and Its Effects on Athletic Performance: A Systematic Review.
AB  - OBJECTIVE: To determine the effects of marijuana on athletic performance. DESIGN:
      We searched MEDLINE, EMBASE, CINAHL, PsycINFO, AMED, and SPORTDiscus from their
      beginning to September 2016. Study quality was assessed using the Cochrane
      collaboration tool for assessing risk of bias and the Cochrane GRADE scale. No
      meta-analyses were performed for this review. SETTING: Subjects in a track, gym,
      or recreational ward. PARTICIPANTS: Any primary study which included male and
      female adults of any athletic background between ages 18 and 65, with no other
      comorbid conditions. INTERVENTIONS: Any primary study which used marijuana
      cigarettes and included a control group. MAIN OUTCOME MEASURES: Vital signs,
      pulmonary measures, physical work capacity, grip strength, and exercise duration
      were determined to be relevant outcomes. RESULTS: Three trials examined marijuana
      and its effects on athletic performance. Two trials had a high risk of bias and 1
      trial had an unclear risk of bias. The effect of marijuana on outcomes including
      heart rate, blood pressure, and exercise duration remains unclear. Low quality
      evidence suggests that treatment, sham, and inactive control groups do not have a
      significant difference for grip strength. Low quality evidence suggests that
      there is an ergogenic effect of treatment demonstrated by increased
      bronchodilation and FEV1 compared with inactive control and that there is an
      ergolytic effect of treatment demonstrated by decreased physical work capacity
      compared with sham and inactive control groups. CONCLUSION: Because the number
      and quality of studies was low, the effects of marijuana on athletic performance
      remain unclear.

PMID- 28767470
TI  - Loss of Smell and Taste After General Anesthesia: A Case Report.
AB  - This case report describes a patient, who lost the ability to smell and taste
      after receiving a propofol-based general anesthesia for a laparoscopic inguinal
      hernia repair. Immediately after the procedure, the patient had anosmia (loss of
      smell), ageusia (loss of taste), and light dysphagia. Assessment by an
      otorhinolaryngologist and the results of a magnetic resonance imaging could not
      clarify the pathology behind these symptoms. Although there are several plausible
      explanations for the patient's anosmia and ageusia (eg, cerebral infarcts, nerve
      damage, chronic sinusitis), the most likely explanation is an uncommon adverse
      drug reaction to the anesthetic agents used during the procedure.

PMID- 28767471
TI  - High-Flow Nasal Oxygen in Patient With Obstructive Sleep Apnea Undergoing Awake
      Craniotomy: A Case Report.
AB  - Patients with obstructive sleep apnea are frequently considered unsuitable
      candidates for awake craniotomy due to anticipated problems with oxygenation,
      ventilation, and a potentially difficult airway. At present, only a handful of
      such accounts exist in the literature. Our report describes the novel use of high
      flow nasal oxygen therapy for a patient with moderate obstructive sleep apnea who
      underwent an awake craniotomy under deep sedation. The intraoperative application
      of high-flow nasal oxygen therapy achieved satisfactory oxygenation, maintained
      the partial carbon dioxide pressure within a reasonable range even during periods
      of deep sedation, permitted responsive patient monitoring during mapping, and
      provided excellent patient and surgeon satisfaction.

PMID- 28767472
TI  - Intrathecal Migration of an Epidural Catheter While Using a Programmed
      Intermittent Epidural Bolus Technique for Labor Analgesia Maintenance: A Case
      Report.
AB  - We describe a case of intrathecal migration of a wire-reinforced epidural
      catheter in a parturient who received epidural labor analgesia. Epidural
      analgesia was initiated with a combined-spinal epidural technique and maintained
      by programmed intermittent epidural boluses. Epidural catheter aspiration after
      insertion was negative for cerebrospinal fluid. The patient's response to the
      first four doses of local anesthetic was consistent with epidural drug delivery.
      After the fifth dose, she developed a complete lower extremity motor block,
      hypotension, and high sensory blockade. Catheter aspiration was then positive for
      cerebrospinal fluid. After symptom resolution, labor pain was successfully
      managed with this inadvertent intrathecal catheter.

PMID- 28767473
TI  - Acquired Hemophilia A After Hepatic Yttrium-90 Radioembolization: A Case Report.
AB  - Acquired hemophilia is a rare but potentially life-threatening bleeding disorder
      caused by the development of autoantibodies (inhibitors) directed against plasma
      coagulation factors, most frequently factor VIII. We report a case of a 65-year
      old man with hepatocellular carcinoma who bled massively after a hepatic Yttrium
      90 radioembolization procedure (Selective Internal Radiation Therapy with Yttrium
      90 Resin Microspheres [SIRTex]). An acquired deficiency of factor VIII was
      diagnosed and successfully treated with recombinant activated factor VII and
      immunosuppression.

PMID- 28767474
TI  - Intraoperative Pulmonary Embolism: A Case Report Emphasizing the Utility of
      Electrocardiogram.
AB  - Pulmonary embolism (PE) is an important cause of perioperative morbidity and
      mortality. In patients with suspected PE, electrocardiogram (ECG) alone is
      thought to have a limited utility due to its low sensitivity and specificity.
      This case report describes a patient with intraoperative PE presenting with
      hypotension and hypoxemia for whom the ECG finding of SIQIIITIII was key in
      identifying acute cor pulmonale. The ECG was paramount in our decision to acquire
      computed tomography angiography to confirm the diagnosis, reinforcing its
      invaluable role in early detection of intraoperative PE.

PMID- 28767475
TI  - Exaggerated Oculocardiac Reflex Elicited by Local Anesthetic Injection of an
      Empty Orbit: A Case Report.
AB  - We report the first description of oculocardiac reflex elicited with injection of
      local anesthetic in an empty orbit, and highlight clinical indicators for
      patients that may be at risk for an exaggerated oculocardiac reflex. We describe
      a patient with prior head and eye trauma treated for anophthalmic socket
      reconstruction at an outpatient eye surgery center. Injection of local anesthetic
      into the empty orbit induced an extended sinus arrest. This exaggerated response
      was avoided in a subsequent surgery by pretreatment with high-dose
      anticholinergics.

PMID- 28767476
TI  - Atypical Neuroleptic Malignant Syndrome: Diagnosis and Proposal for an Expanded
      Treatment Algorithm: A Case Report.
AB  - Neuroleptic malignant syndrome (NMS) in the absence of an elevated creatine
      kinase is atypical and more difficult to diagnose. We present a patient with NMS
      significant risk factors who developed atypical NMS 6 days after a liver
      transplant. Symptoms of hyperthermia, altered mental status, dyskinesia, and
      autonomic instability (hypertension and tachycardia) coincided with promethazine
      administration, with rapid progression to fulminant NMS with lead pipe rigidity
      after a single injection of intramuscular ziprasidone. Rapid diagnosis and
      management resulted in full patient recovery. Differential diagnoses for NMS are
      discussed and a treatment algorithm is proposed.

PMID- 28767477
TI  - A Simple and Effective Way to Secure a Laryngeal Mask Airway in Place.

PMID- 28767478
TI  - Ultrasound-Guided Serratus Plane Block and Fast-Track Tracheal Extubation in the
      Operating Room for Thoracic Trauma Patients: A Case Report.
AB  - Painful rib fractures may be a factor in trauma patients remaining intubated and
      being given postoperative mechanical ventilation after emergency surgery.
      Regional techniques could provide sufficient analgesia in these patients to
      enable weaning and extubation and thus prevent or minimize complications related
      to prolonged ventilatory support. We describe a trauma patient with multiple rib
      fractures requiring an emergency splenectomy for whom an ultrasound-guided
      serratus plane block provided good quality pain relief for his rib fractures and
      enabled fast-track extubation in the operating room.

PMID- 28767480
TI  - Combined Selective Nerve Blockade and Local Infiltration Analgesia in a Total
      Shoulder Arthroplasty Patient With Chronic Pain and Severe Restrictive Lung
      Disease: A Case Report.
AB  - Interscalene brachial plexus block is considered the most complete postoperative
      analgesia after total shoulder arthroplasty. Interscalene brachial plexus block
      induced ipsilateral hemidiaphragmatic paralysis may not be tolerated in patients
      with preexisting pulmonary disease. Selective distal nerve blocks avoid the risk
      of phrenic nerve block; however, they may provide incomplete analgesia to the
      glenohumeral joint. We report a case of combined selective suprascapular and
      axillary nerve blockade in combination with local infiltration analgesia in a
      patient with severe lung disease undergoing total shoulder arthroplasty. This
      case highlights the local infiltration analgesia technique of the shoulder joint
      and current diaphragm-sparing regional anesthesia blocks.

PMID- 28767479
TI  - Resistance to Propofol Induction in a Patient Taking Modafinil: A Case Report.
AB  - After sedation with midazolam, induction of anesthesia with propofol was
      attempted in a patient taking modafinil. However, even after administration of a
      total of 6 mg/kg propofol IV, the patient continued to respond to tactile
      stimulation. Concurrently, the bispectral index was 72. Subsequent administration
      of low concentration sevoflurane by facemask induced an anesthetic depth that
      allowed unproblematic insertion of a laryngeal mask airway. Anesthesia for
      ophthalmologic surgery was maintained with sevoflurane. Modafinil may have caused
      resistance to propofol because of its effect on neural pathways that activate
      consciousness. The concentration of sevoflurane required to induce or maintain
      anesthesia remained unaltered.

PMID- 28767481
TI  - When Faced With Anesthetizing an Infant With PHACE Syndrome: Watch Out for an
      Airway-Occluding Subglottic Hemangioma!

PMID- 28767482
TI  - High-Intensity Exercise Induced Oxidative Stress and Skeletal Muscle Damage in
      Postpubertal Boys and Girls: A Comparative Study.
AB  - Pal, S, Chaki, B, Chattopadhyay, S, and Bandyopadhyay, A. High-intensity exercise
      induced oxidative stress and skeletal muscle damage in post-pubertal boys and
      girls: a comparative study. J Strength Cond Res 32(4): 1045-1052, 2018-The
      purpose of this study was to examine the sex variation in high-intensity exercise
      induced oxidative stress and muscle damage among 44 sedentary postpubertal boys
      and girls through estimation of postexercise release pattern of muscle damage
      markers like creatine kinase, lactate dehydrogenase (LDH), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and oxidative stress
      markers like extent of lipid peroxidation (thiobarbituric acid-reactive
      substances) and catalase activity. Muscle damage markers like creatine kinase,
      LDH, ALT, and AST were measured before, immediately after, and 24 and 48 hours
      after high-intensity incremental treadmill running. Oxidative stress markers like
      thiobarbituric acid-reactive substances and catalase activity were estimated
      before and immediately after the exercise. Lipid peroxidation and serum catalase
      activity increased significantly in both groups after exercise (p < 0.001) with
      postexercise values and percentage increase significantly higher in postpubertal
      boys as compared to girls (p < 0.001). Creatine kinase and LDH activity also
      increased significantly above pre-exercise level at 24 and 48 hours after
      exercise in both the sexes, (p < 0.001) with values significantly higher for boys
      than the girls (p < 0.001). Although ALT and AST increased significantly in both
      the groups after exercise, the pattern of postexercise release of these markers
      were found to be similar in both the groups. Accordingly, it has been concluded
      from the present investigation that high-intensity exercise induces significant
      oxidative stress and increases indices of skeletal muscle damage in both
      postpubertal girls and boys. However, postpubertal girls are relatively better
      protected from oxidative stress and muscle damage as compared to the boys of
      similar age and physical activity level. It is further evident that sex
      difference may not be apparent for all the biomarkers of muscle damage in this
      age group.

PMID- 28767483
TI  - Activity profiles in U17, U20 and senior women's Brazilian National soccer teams
      during international competitions: Are there meaningful differences?
AB  - The aim of this study was to compare locomotor activity profiles of Brazilian top
      class female soccer players competing at distinct age brackets (U17, U20, and
      Senior). External match load of 14 U17, 14 U20, and 17 Senior female soccer
      players competing in 6-7 full official international matches were assessed using
      global positioning systems (GPS). Total distance covered, distance covered in
      high intensity (HID:15.6-20 kmh), distance covered in sprints (sprint:>20 kmh),
      number of accelerations (Acc)>1 ms, decelerations (Dec) >-1 ms, and Player Load
      generally increased across the age brackets (U17<U20<Senior). For all playing
      positions, Senior athletes presented greater total distance, accelerations, and
      decelerations than U20 players. For high-intensity distance and sprints, only
      central defender and midfielder senior players presented greater values than U20
      players. Senior players demonstrated higher values in all locomotor activities in
      comparison to U17 players, irrespective of playing positions. Except for central
      defenders that presented similar total distance, sprint distance, and number of
      accelerations between U20 and U17, the majority of match external loads evaluated
      in all playing positions were greater in U20 than in U17 players. These results
      provide useful information for player development and should be used to establish
      appropriate match-specific conditioning drills according to age categories.

PMID- 28767484
TI  - Noninvasive cardiovascular imaging for evaluating subclinical target organ damage
      in hypertensive patients: a consensus article from the European Association of
      Cardiovascular Imaging, the European Society of Cardiology Council on
      Hypertension and the European Society of Hypertension.
AB  - : Arterial hypertension accounts for the largest amount of attributable
      cardiovascular mortality worldwide, and risk stratification in hypertensive
      patients is of crucial importance to manage treatment and prevent adverse events.
      Asymptomatic involvement of different organs in patients affected by hypertension
      represents an independent determinant of cardiovascular risk, and the
      identification of target organ damage is recommended to further reclassify
      patients' risk. Noninvasive cardiovascular imaging is progressively being used
      and continues to provide new technological opportunities to target organ damage
      evaluation at early stage. The aim of this article is to provide the community of
      cardiology with an update on appropriate and justified use of noninvasive imaging
      tests in the growing population of hypertensive patients.

PMID- 28767485
TI  - Antihypertensive therapy: strategic withdrawal or a mandatory life sentence?

PMID- 28767486
TI  - Effects of renal denervation on short-term blood pressure variability: lack of
      meta-analytic evidence.

PMID- 28767487
TI  - The Strong Heart Study: adding biological plausibility to the red meat
      cardiovascular disease association.

PMID- 28767488
TI  - Blood pressure, heart rate, and double product: lessons learned from Japan.

PMID- 28767491
TI  - Medical Student Perceptions of Global Surgery at an Academic Institution:
      Identifying Gaps in Global Health Education.
AB  - PURPOSE: Robust global health demands access to safe, affordable, timely surgical
      care for all. The long-term success of global surgery requires medical students
      to understand and engage with this emerging field. The authors characterized
      medical students' perceptions of surgical care relative to other fields within
      global health. METHOD: An optional, anonymous survey was given to all Johns
      Hopkins medical students from February to March 2016 to assess perceptions of
      surgical care and its role in global health. RESULTS: Of 480 students, 365 (76%)
      completed the survey, with 150 (41%) reporting global health interests. One-third
      (34%) of responding students felt that surgical care is one of two fields with
      the greatest potential global health impact in the future, second to infectious
      disease (49%). A minority (28%) correctly identified that trauma results in more
      deaths worldwide than obstetric complications or HIV/AIDS, tuberculosis, and
      malaria combined. Relative to other examined fields, students perceived surgical
      care as the least preventive and cost-effective, and few students (3%) considered
      adequate surgical care the best indicator of a robust health care system.
      Students believed that practicing in a surgical field was least amenable to
      pursuing a global health career, citing several barriers. CONCLUSIONS: Medical
      students have several perceptions of global surgery that contradict current
      evidence and literature, which may have implications for their career choices.
      Opportunities to improve students' global health knowledge and awareness of
      global surgery career paths include updating curricula, fostering meaningful
      international academic opportunities, and creating centers of global surgery and
      global health consortia.

PMID- 28767492
TI  - Apprenticeship to Entrustment: A Model for Clinical Education.

PMID- 28767493
TI  - Transgender and Gender Nonconforming Patient Experiences at a Family Medicine
      Clinic.
AB  - PURPOSE: Transgender and gender nonconforming (TGNC) patients have a wide array
      of often negative experiences when accessing health care, and may encounter
      insensitive or subcompetent care; thus, the authors conducted a qualitative study
      with patients at one family medicine residency clinic to assess how primary care
      clinics can improve care for TGNC patients. METHOD: In 2015, the authors held
      three separate focus groups at Smiley's Family Medicine Clinic in Minneapolis,
      Minnesota. They invited diverse TGNC participants who have accessed TGNC-related
      and/or primary care at Smiley's. The authors analyzed and coded data using a
      grounded theory approach with NVivo10 (QSR). The authors also administered short
      demographic questionnaires and analyzed the results with REDCap. RESULTS: Twenty
      three patients participated in the focus groups, and 22 completed the survey.
      Gender identities among the participants were diverse. Four main themes emerged:
      (1) shared negative experiences with health care, (2) the need for sensitive and
      inclusive primary care, (3) defining TGNC-sensitive care, and (4) the challenges
      of mainstreaming TGNC-competent care into primary care settings. CONCLUSIONS:
      Providing sensitive and competent primary care to TGNC patients involves allowing
      patients to self-identify, respecting the gender identities of every patient, and
      focusing on the whole person-not the trans status of the patient. Education and
      training on TGNC care at a clinic-wide level is needed.

PMID- 28767494
TI  - The Daunting Career of the Physician-Investigator.
AB  - For many years, physician-investigators have had a particularly difficult time
      with their academic careers, so that they have been labeled an endangered
      species. In this Invited Commentary, the author defines three career paths for
      physician-investigators-clinical researcher, clinician-scientist, and physician
      scientist. Each of these pathways has common and distinct challenges that should
      be studied and potential improvements that should be evaluated through pilot
      research projects.The first challenge that all physician-investigators face is
      securing funding. Physicians are funded by their clinical activities, which often
      lures physician-investigators to increase their clinical work, particularly when
      research funding from the National Institutes of Health is difficult to secure
      and seemingly arbitrarily granted. The second challenge is an appointments,
      promotion, and tenure system that is not responsive to the needs of faculty
      working across clinical care and research, particularly when it comes to
      evaluating team science. Physician-investigators not working full-time in either
      discipline then may have trouble being promoted. The third challenge is the
      increasing burdens of clinical activities, particularly with the advent of
      electronic medical records.In this issue, two articles address overcoming the
      challenges faced by physician-investigators, one from the National Institutes of
      Health to grow the workforce and the other to offer organizational and individual
      solutions to support these investigators in faculty roles. These solutions are
      encouraging, but data about the extent of the challenges and the potential
      effects of the solutions are needed to make the physician-investigator career
      path less daunting.

PMID- 28767495
TI  - Making the First Cut: An Analysis of Academic Medicine Editors' Reasons for Not
      Sending Manuscripts Out for External Peer Review.
AB  - PURPOSE: Manuscripts submitted to Academic Medicine (AM) undergo an internal
      editor review to determine whether they will be sent for external peer review.
      Increasingly, manuscripts are rejected at this early stage. This study seeks to
      inform scholars about common reasons for internal editor review rejections,
      increase transparency of the process, and provide suggestions for improving
      submissions. METHOD: A mixed-methods approach was used to retrospectively analyze
      editors' free-text comments. Descriptive content analysis was performed of
      editors' comments for 369 manuscripts submitted between December 2014 and
      December 2015, and rejected prior to external peer review from AM. Comments were
      analyzed, categorized, and counted for explicit reasons for rejection. RESULTS:
      Nine categories of rejection reasons were identified: ineffective study question
      and/or design (338; 92%); suboptimal data collection process (180; 49%); weak
      discussion and/or conclusions (139; 37%); unimportant or irrelevant topic to the
      journal's mission (137; 37%); weak data analysis and/or presentation of results
      (120; 33%); text difficult to follow, to understand (89; 24%); inadequate or
      incomplete introduction (67; 18%); other publishing considerations (42; 11%); and
      issues with scientific conduct (20; 5%). Manuscripts had, on average, three or
      more reasons for rejection. CONCLUSIONS: Findings suggest that clear
      identification of a research question that is addressed by a well-designed study
      methodology on a topic aligned with the mission of the journal would address many
      of the problems that lead to rejection through the internal review process. The
      findings also align with research on external peer review.

PMID- 28767496
TI  - Situating Remediation: Accommodating Success and Failure in Medical Education
      Systems.
AB  - There has been a widespread shift to competency-based medical education (CBME) in
      the United States and Canada. Much of the CBME discourse has focused on the
      successful learner, with relatively little attention paid to what happens in CBME
      systems when learners stumble or fail. Emerging issues, such as the well
      documented problem of "failure to fail" and concerns about litigious learners,
      have highlighted a need for well-defined and integrated frameworks to support and
      guide strategic approaches to the remediation of struggling medical learners.This
      Perspective sets out a conceptual review of current practices and an argument for
      a holistic approach to remediation in the context of their parent medical
      education systems. The authors propose parameters for integrating remediation
      into CBME and describe a model based on five zones of practice along with the
      rules of engagement associated with each zone. The zones are "normal" curriculum,
      corrective action, remediation, probation, and exclusion.The authors argue that,
      by linking and integrating theory and practice in remediation with CBME, a more
      integrated systems-level response to differing degrees of learner difficulty and
      failure can be developed. The proposed model demonstrates how educational
      practice in different zones is based on different rules, roles, responsibilities,
      and thresholds for moving between zones. A model such as this can help medical
      educators and medical education leaders take a more integrated approach to
      learners' failures as well as their successes by being more explicit about the
      rules of engagement that apply in different circumstances across the competency
      continuum.

PMID- 28767498
TI  - The Road to Rural Primary Care: A Narrative Review of Factors That Help Develop,
      Recruit, and Retain Rural Primary Care Physicians.
AB  - PURPOSE: To examine the literature documenting successes in recruiting and
      retaining rural primary care physicians. METHOD: The authors conducted a
      narrative review of literature on individual, educational, and professional
      characteristics and experiences that lead to recruitment and retention of rural
      primary care physicians. In May 2016, they searched MEDLINE, PubMed, CINAHL,
      ERIC, Web of Science, Google Scholar, the Grey Literature Report, and reference
      lists of included studies for literature published in or after 1990 in the United
      States, Canada, or Australia. The authors identified 83 articles meeting
      inclusion criteria. They synthesized results and developed a theoretical model
      that proposes how the findings interact and influence rural recruitment and
      retention. RESULTS: The authors' proposed theoretical model suggests factors
      interact across multiple dimensions to facilitate the development of a rural
      physician identity. Rural upbringing, personal attributes, positive rural
      exposure, preparation for rural life and medicine, partner receptivity to rural
      living, financial incentives, integration into rural communities, and good work
      life balance influence recruitment and retention. However, attending medical
      schools and/or residencies with a rural emphasis and participating in rural
      training may reflect, rather than produce, intention for rural practice.
      CONCLUSIONS: Many factors enhance rural physician identity development and
      influence whether physicians enter, remain in, and thrive in rural practice. To
      help trainees and young physicians develop the professional identity of a rural
      physician, multifactorial medical training approaches aimed at encouraging long
      term rural practice should focus on rural-specific clinical and nonclinical
      competencies while providing trainees with positive rural experiences.

PMID- 28767497
TI  - Mediators of Racial/Ethnic Disparities in Mentored K Award Receipt Among U.S.
      Medical School Graduates.
AB  - PURPOSE: Mentored K (K01/K08/K23) career development awards are positively
      associated with physicians' success as independent investigators; however,
      individuals in some racial/ethnic groups are less likely to receive this federal
      funding. The authors sought to identify variables that explain (mediate) the
      association between race/ethnicity and mentored K award receipt among U.S.
      Liaison Committee for Medical Education-accredited medical school graduates who
      planned research-related careers. METHOD: The authors analyzed deidentified data
      from the Association of American Medical Colleges and the National Institutes of
      Health Information for Management, Planning, Analysis, and Coordination II grants
      database for a national cohort of 28,690 graduates from 1997-2004 who planned
      research-related careers, followed through August 2014. The authors examined 10
      potential mediators (4 research activities, 2 academic performance measures,
      medical school research intensity, degree program, debt, and specialty) of the
      association between race/ethnicity and mentored K award receipt in models
      comparing underrepresented minorities in medicine (URM) and non-URM graduates.
      RESULTS: Among 27,521 graduates with complete data (95.9% of study-eligible
      graduates), 1,147 (4.2%) received mentored K awards (79/3,341 [2.4%] URM;
      1,068/24,180 [4.4%] non-URM). All variables except debt were significant
      mediators; together they explained 96.2% (95%, CI 79.1%-100%) of the association
      between race/ethnicity and mentored K award. CONCLUSIONS: Research-related
      activities during/after medical school and standardized academic measures largely
      explained the association between race/ethnicity and mentored K award in this
      national cohort. Interventions targeting these mediators could mitigate
      racial/ethnic disparities in the federally funded physician-scientist research
      workforce.

PMID- 28767501
TI  - Endoscopic gastroenterostomy: techniques and review.
AB  - PURPOSE OF REVIEW: Gastric outlet obstruction (GOO) can result from benign and
      malignant causes. Until recently, surgical gastrojejunostomy was the treatment of
      choice for patient with benign and malignant GOO with a good functional status.
      Endoscopic placement of luminal self-expandable metal stents is currently widely
      accepted as the first line of treatment for malignant GOO because of its
      effectiveness and minimally invasive nature. The main shortcoming of luminal
      stents is the high incidence of recurrent GOO most commonly because of tumor
      ingrowth/overgrowth. More recently, endoscopic ultrasound (EUS)-guided
      gastroenterostomy (EUS-GE) has emerged as an alternative to both luminal stent
      placement and surgical gastrojejunostomy. Advantages of EUS-GE include its
      minimally invasive nature, efficacy and low incidence of recurrent GOO in cancer
      patient. We will describe five different techniques to perform this novel and
      rapidly evolving procedure using a biflanged, lumen-apposing metal stent and
      compare benefits and risks of each approach. These approaches include antegrade
      EUS-GE or 'traditional/downstream' and 'rendezvous' methods, retrograde EUS-GE or
      'enterogastrostomy,'17 (EPASS), and antegrade EUS-GE 'direct' method. RECENT
      FINDINGS: A preprocedural computed tomography scan allows the proximity of the
      duodenum or jejunum to the stomach to be determined and to assess for the
      presence of significant ascites, which is a contraindication to EUS-GE. Technical
      success rates even in the early studies approximate 90%, regardless of the
      technique used. Clinical success rates have been exceptionally high as well, with
      only a minority of patients experiencing persistent symptoms despite technical
      success. One procedure-related death has been reported so far with an overall low
      morbidity. Pain, bleeding, pneumoperitoneum and peritonitis have been reported in
      one patient each. However, duration of follow-up in these studies has been short.
      SUMMARY: We describe five different techniques to performing EUS-GE. Early
      studies show excellent efficacy. Stent misdeployment/displacement is the most
      frequent relevant adverse event. Prospective and preferably randomized trials
      with comparison to endoluminal enteral stents and surgical gastroenterostomy are
      needed.

PMID- 28767499
TI  - Clinician-Investigator Training and the Need to Pilot New Approaches to
      Recruiting and Retaining This Workforce.
AB  - Clinician-investigators, also called physician-scientists, offer critical
      knowledge and perspectives that benefit research on basic science mechanisms,
      improved diagnostic and therapeutic approaches, population and outcomes medicine,
      health policy, and health services, yet few clinically trained health
      professionals pursue a research career. Sustaining this workforce requires
      attention to the unique challenges faced by investigators who must achieve
      clinical and research competence during training and their careers. These
      challenges include the duration of required clinical training, limited or
      discontinuous research opportunities, high levels of educational debt, balancing
      the dual obligations and rewards of clinical care and research, competition for
      research funding, and the need for leadership development after training. Women
      and individuals from underrepresented racial and ethnic groups comprise a small
      percentage of this workforce.The authors summarize the recent literature on
      training for clinician-investigators, emphasizing approaches with encouraging
      outcomes that warrant broader implementation. Using this overview as background,
      they convened three workshops at the National Institutes of Health in 2016 to
      identify and refine key priorities for potential new pilot programs to recruit
      and retain the clinician-investigator workforce. From these workshops emerged
      three priorities for future pilot programs: (1) support for research in
      residency, (2) new research on-ramps for health professionals at multiple career
      stages, and (3) national networks to diversify and sustain clinician-investigator
      faculty. Implementation of any pilot program will require coordinated commitment
      from academic health centers, medical licensing/certification boards,
      professional societies, and clinician-investigators themselves, in addition to
      support from the National Institutes of Health.

PMID- 28767502
TI  - Is Swimming Safe in Heart Failure? A Systematic Review.
AB  - It is not clear whether swimming is safe in patients with chronic heart failure.
      Ten studies examining the hemodynamic effects of acute water immersion (WI) (155
      patients; average age 60 years; 86% male; mean left ventricular ejection fraction
      (LVEF) 29%) and 6 randomized controlled trials of rehabilitation comparing
      swimming with either medical treatment only (n = 3) or cycling (n = 1) or aerobic
      exercise (n = 2), (136 patients, average age 59 years; 84% male, mean LVEF 31%)
      were considered. In 7 studies of warm WI (30-35 degrees C): heart rate (HR) fell
      (2% to -15%), and both cardiac output (CO) (7-37%) and stroke volume (SV)
      increased (13-41%). In 1 study of hot WI (41 degrees C), systemic vascular
      resistance (SVR) fell (41%) and HR increased (33%). In 2 studies of cold WI (12
      22 degrees C), there were no consistent effects on HR and CO. Compared with
      medical management, swimming led to a greater increase in peak VO2 (7-14%) and 6
      minute walk test (6MWT) (7-13%). Compared with cycle training, combined swimming
      and cycle training led to a greater reduction in resting HR (16%), a greater
      increase in resting SV (23%) and SVR (15%), but no changes in resting CO and a
      lesser increase in peak VO2 (6%). Compared with aerobic training, combined
      swimming and aerobic training lead to a reduction in resting HR (19%) and SVR
      (54%) and a greater increase in SV (34%), resting CO (28%), LVEF (9%), and 6MWT
      (70%). Although swimming appears to be safe, the studies conducted have been
      small, very heterogeneous, and inconclusive.

PMID- 28767503
TI  - Neuroendovascular Surgery for the Treatment of Ischemic Stroke.
AB  - This review discusses modern therapeutic interventions for acute ischemic stroke
      with a focus on endovascular therapy. In 2015, the American Heart Association
      made major changes to the guidelines for the endovascular treatment of acute
      ischemic stroke. The Class IA indications for endovascular therapy of stroke
      patients include symptom onset within 6 h, proven large vessel occlusion of an
      artery in the anterior circulation, and the use of a stent retriever as part of
      the mechanical thrombectomy. Advanced perfusion imaging helps identify patients
      with a low ratio of ischemic core to salvageable penumbra. Equally important to
      overall clinical outcome is the organization of comprehensive stroke centers and
      the recent advent of the mobile stroke unit. Future clinical endovascular stroke
      trials will help us to better understand the role of endovascular interventions.

PMID- 28767504
TI  - Echocardiography in the Evaluation of Pulmonary Embolism.
AB  - Pulmonary embolism is a major cause of mortality. Acute pulmonary embolism also
      encompasses a wide clinical spectrum of severity, ranging from asymptomatic
      silent disease to hemodynamic instability and shock. Echocardiography is a useful
      modality to improve treatment strategies for pulmonary embolus. Echocardiography
      plays a role in risk stratification at the time of diagnosis. The evaluation of
      the right ventricle (RV) has evolved over time. RV variables evaluated by
      echocardiography include RV size, RV/left ventricular ratio, RV fractional area
      of change, tricuspid annular plane systolic excursion, RV systolic pressure, and
      RV Tei index. It has also been used in determining treatment strategies and
      following the success of treatment. Multiple echocardiographic criteria have been
      studied to improve risk stratification and outcomes from pulmonary embolism.
      Further studies are needed to assess the appropriate quantitative
      echocardiographic parameters.

PMID- 28767506
TI  - Defining chronic pain in epidemiological studies: a systematic review and meta
      analysis.
AB  - The objective was to document the operational definitions applied in
      epidemiological studies of chronic pain and to examine whether pain definitions
      and other methodological factors are systematically related to prevalence
      estimates. MEDLINE, EMBASE, and PsychINFO were searched for original research
      reports with study samples of at least 1000 individuals, excluding studies of
      less than 5 out of 15 selected body regions and studies solely concerned with
      specific pain conditions. Meta-analyses and meta-regressions were applied with
      random effects models; covariates were geography, sampling year, survey method,
      sampling frame, participation rate, percentage women of all participants, pain
      duration, and pain location. Of 6791 hits, 86 studies were included in the
      syntheses. The phrasing, content, and combinations of the chronic pain definition
      criteria were highly inconsistent, with virtually no 2 studies from independent
      research groups using the exact same criteria. Prevalence estimates ranged from
      8.7% to 64.4%, with a pooled mean of 31%. Huge heterogeneity was shown in all
      forest plots. Prevalence estimates were significantly related to survey method
      (beta = -10.8 [95% confidence interval: -17.2 to -4.4]), but it only counted for
      a small fraction of the between-studies variation in the estimates. There were
      also interaction effect of survey method by sex (female-male prevalence ratio
      [95% confidence interval]: questionnaire = 1.20 [1.16 to 1.25], and interview =
      1.38 [1.29 to 1.47]). The other covariates investigated were not significantly
      related to the prevalence estimates. Researchers and clinicians should be aware
      of the probability that interview survey method of collecting data may give lower
      chronic pain reporting than questionnaire survey method and that this effect may
      be stronger in men than women.

PMID- 28767507
TI  - Bleeding out the quality-adjusted life years: evaluating the burden of primary
      dysmenorrhea using time trade-off and willingness-to-pay methods.
AB  - Primary dysmenorrhea (PD), or painful menstruation in the absence of identified
      uterine pathology, affects 5 to 9 in every 10 reproductive-aged women. Despite
      its high prevalence, just a few studies with very small patient numbers have
      focused on health-related quality of life impairment in PD. We aimed to assess
      health-related quality of life values for a severe and a mild hypothetical PD
      health state using 10-year time trade-off and willingness-to-pay methods. In
      2015, a nationwide convenience sample of women, aged between 18 and 40 years, was
      recruited using an Internet-based cross-sectional survey in Hungary. Respondents
      with a known history of secondary dysmenorrhea were excluded. Data on 1836 and
      160 women, with and without a history of PD, respectively, were analysed. Mean
      utility values for the severe and mild health states were 0.85 (median 0.95) and
      0.94 (median 1), respectively. Participants were willing to pay a mean of
      &OV0556;1127 (median &OV0556;161) and &OV0556;142 (median &OV0556;16) for a
      complete cure from the severe and mild PD health states. Compared with the non-PD
      group, women with PD valued both health states worse according to willingness to
      pay (P < 0.05) but similar in the time trade-off. It seems that PD substantially
      contributes to the quality-adjusted life year loss in this age group, which is
      comparable with losses from chronic diseases such as type 1 diabetes, asthma,
      atopic eczema, or chronic migraine. Our findings provide a useful input to cost
      effectiveness and cost-benefit analyses of PD treatments.

PMID- 28767505
TI  - Age-dependent plasticity in endocannabinoid modulation of pain processing through
      postnatal development.
AB  - Significant age- and experience-dependent remodelling of spinal and supraspinal
      neural networks occur, resulting in altered pain responses in early life. In
      adults, endogenous opioid peptide and endocannabinoid (ECs) pain control systems
      exist which modify pain responses, but the role they play in acute responses to
      pain and postnatal neurodevelopment is unknown. Here, we have studied the
      changing role of the ECs in the brainstem nuclei essential for the control of
      nociception from birth to adulthood in both rats and humans. Using in vivo
      electrophysiology, we show that substantial functional changes occur in the
      effect of microinjection of ECs receptor agonists and antagonists in the
      periaqueductal grey (PAG) and rostroventral medulla (RVM), both of which play
      central roles in the supraspinal control of pain and the maintenance of chronic
      pain states in adulthood. We show that in immature PAG and RVM, the orphan
      receptor, GPR55, is able to mediate profound analgesia which is absent in adults.
      We show that tissue levels of endocannabinoid neurotransmitters, anandamide and 2
      arachidonoylglycerol, within the PAG and RVM are developmentally regulated (using
      mass spectrometry). The expression patterns and levels of ECs enzymes and
      receptors were assessed using quantitative PCR and immunohistochemistry. In human
      brainstem, we show age-related alterations in the expression of key enzymes and
      receptors involved in ECs function using PCR and in situ hybridisation. These
      data reveal that significant changes on ECs that to this point have been unknown
      and which shed new light into the complex neurochemical changes that permit
      normal, mature responses to pain.

PMID- 28767508
TI  - The role of spatial frequency information in the decoding of facial expressions
      of pain: a novel hybrid task.
AB  - Spatial frequency (SF) information contributes to the recognition of facial
      expressions, including pain. Low-SF encodes facial configuration and structure
      and often dominates over high-SF information, which encodes fine details in
      facial features. This low-SF preference has not been investigated within the
      context of pain. In this study, we investigated whether perpetual preference
      differences exist for low-SF and high-SF pain information. A novel hybrid
      expression paradigm was used in which 2 different expressions, one containing low
      SF information and the other high-SF information, were combined in a facial
      hybrid. Participants are instructed to identify the core expression contained
      within the hybrid, allowing for the measurement of SF information preference.
      Three experiments were conducted (46 participants in each) that varied the
      expressions within the hybrid faces: respectively pain-neutral, pain-fear, and
      pain-happiness. In order to measure the temporal aspects of image processing,
      each hybrid image was presented for 33, 67, 150, and 300 ms. As expected,
      identification of pain and other expressions was dominated by low-SF information
      across the 3 experiments. The low-SF preference was largest when the presentation
      of hybrid faces was brief and reduced as the presentation duration increased. A
      sex difference was also found in experiment 1. For women, the low-SF preference
      was dampened by high-SF pain information, when viewing low-SF neutral
      expressions. These results not only confirm the role that SF information has in
      the recognition of pain in facial expressions but suggests that in some
      situations, there may be sex differences in how pain is communicated.

PMID- 28767509
TI  - Persistent postoperative pain after cardiac surgery: a systematic review with
      meta-analysis regarding incidence and pain intensity.
AB  - Persistent postoperative pain (PPP) has been described as a complication of
      cardiac surgery (CS). We aimed to study PPP after CS (PPPCS) by conducting a
      systematic review of the literature regarding its incidence, intensity, location,
      and the presence of neuropathic pain, according to the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses. The review comprised 3 phases: a
      methodological assessment of 6 different databases identifying potential articles
      and screening for inclusion criteria by 2 independent reviewers; data extraction;
      and study quality assessment. Meta-analysis was used to estimate the pooled
      incidence rates using a random effects model. We have identified 442 potentially
      relevant studies through database searching. A total of 23 studies (involving
      11,057 patients) met our inclusion criteria. Persistent postoperative pain
      affects 37% patients in the first 6 months after CS, and it remains present more
      than 2 years after CS in 17%. The reported incidence of PPP during the first 6
      months after CS increased in recent years. Globally, approximately half of the
      patients with PPPCS reported moderate to severe pain. Chest is the main location
      of PPPCS followed by the leg; neuropathic pain is present in the majority of the
      patients. This is the first systematic review and meta-analysis to provide
      estimates regarding incidence and intensity of PPPCS, which elucidates its
      relevance. There is an urgent need for adequate treatment and follow-up in
      patients with PPPCS.

PMID- 28767510
TI  - Psychological interventions that target sleep reduce pain catastrophizing in knee
      osteoarthritis.
AB  - Pain catastrophizing is a significant risk factor for patients with knee
      osteoarthritis (KOA) and thus is a target for many psychological interventions
      for pain. This study examined if interventions targeting sleep found to be
      effective in improving sleep in KOA also reduce pain catastrophizing measured as
      a trait through the pain catastrophizing scale and measured as a daytime and
      nocturnal state through daily diaries. Secondary analyses were conducted on data
      collected as part of a randomized controlled trial assessing the effectiveness of
      cognitive behavioral therapy for insomnia in patients with KOA at 5 different
      time points: pretreatment, midtreatment and posttreatment and at 3- and 6-month
      follow-up. One hundred patients diagnosed with KOA and insomnia were randomized
      to receive either 8 sessions of cognitive behavioral therapy for insomnia or a
      placebo intervention of behavioral desensitization. Multilevel modeling revealed
      that both intervention groups showed a significant reduction pretreatment to
      posttreatment in all 3 measures of pain catastrophizing and maintained stable
      levels through the 6-month follow-up. Increased sleep continuity early in
      treatment (pretreatment to midtreatment), but not reductions in pain, was
      associated with a reduction in trait and nocturnal catastrophizing later in
      treatment (midtreatment to posttreatment). These results suggest that short
      interventions focusing on sleep can significantly reduce pain catastrophizing
      even in a clinical population with low baseline levels of catastrophizing,
      possibly through improving sleep continuity.

PMID- 28767511
TI  - Protein kinase A regulates inflammatory pain sensitization by modulating HCN2
      channel activity in nociceptive sensory neurons.
AB  - Several studies implicated cyclic adenosine monophosphate (cAMP) as an important
      second messenger for regulating nociceptor sensitization, but downstream targets
      of this signaling pathway which contribute to neuronal plasticity are not well
      understood. We used a Cre/loxP-based strategy to disable the function of either
      HCN2 or PKA selectively in a subset of peripheral nociceptive neurons and
      analyzed the nociceptive responses in both transgenic lines. A near-complete lack
      of sensitization was observed in both mutant strains when peripheral inflammation
      was induced by an intradermal injection of 8br-cAMP. The lack of HCN2 as well as
      the inhibition of PKA eliminated the cAMP-mediated increase of calcium transients
      in dorsal root ganglion neurons. Facilitation of Ih via cAMP, a hallmark of the
      Ih current, was abolished in neurons without PKA activity. Collectively, these
      results show a significant contribution of both genes to inflammatory pain and
      suggest that PKA-dependent activation of HCN2 underlies cAMP-triggered neuronal
      sensitization.

PMID- 28767512
TI  - Dissecting the role of the CRMP2-neurofibromin complex on pain behaviors.
AB  - Neurofibromatosis type 1 (NF1), a genetic disorder linked to inactivating
      mutations or a homozygous deletion of the Nf1 gene, is characterized by
      tumorigenesis, cognitive dysfunction, seizures, migraine, and pain. Omic studies
      on human NF1 tissues identified an increase in the expression of collapsin
      response mediator protein 2 (CRMP2), a cytosolic protein reported to regulate the
      trafficking and activity of presynaptic N-type voltage-gated calcium (Cav2.2)
      channels. Because neurofibromin, the protein product of the Nf1 gene, binds to
      and inhibits CRMP2, the neurofibromin-CRMP2 signaling cascade will likely affect
      Ca channel activity and regulate nociceptive neurotransmission and in vivo
      responses to noxious stimulation. Here, we investigated the function of
      neurofibromin-CRMP2 interaction on Cav2.2. Mapping of >275 peptides between
      neurofibromin and CRMP2 identified a 15-amino acid CRMP2-derived peptide that,
      when fused to the tat transduction domain of HIV-1, inhibited Ca influx in dorsal
      root ganglion neurons. This peptide mimics the negative regulation of CRMP2
      activity by neurofibromin. Neurons treated with tat-CRMP2/neurofibromin
      regulating peptide 1 (t-CNRP1) exhibited a decreased Cav2.2 membrane
      localization, and uncoupling of neurofibromin-CRMP2 and CRMP2-Cav2.2
      interactions. Proteomic analysis of a nanodisc-solubilized membrane protein
      library identified syntaxin 1A as a novel CRMP2-binding protein whose interaction
      with CRMP2 was strengthened in neurofibromin-depleted cells and reduced by t
      CNRP1. Stimulus-evoked release of calcitonin gene-related peptide from lumbar
      spinal cord slices was inhibited by t-CNRP1. Intrathecal administration of t
      CNRP1 was antinociceptive in experimental models of inflammatory, postsurgical,
      and neuropathic pain. Our results demonstrate the utility of t-CNRP1 to inhibit
      CRMP2 protein-protein interactions for the potential treatment of pain.

PMID- 28767513
TI  - Shedding light on the contribution of different c-fibre nociceptors to
      nocifensive behavior.

PMID- 28767514
TI  - Interrelationships Between Walkability, Air Pollution, Greenness, and Body Mass
      Index.
AB  - BACKGROUND: Recent studies have linked urban environmental factors and body mass
      index (BMI); however, such factors are often examined in isolation, ignoring
      correlations across exposures. METHODS: Using data on Nurses' Health Study
      participants living in the Northeastern United States in 2006, we estimated
      associations between neighborhood walkability (a composite of population density,
      street connectivity, and business access), greenness (from satellite imagery),
      and ambient air pollution (from satellite-based spatiotemporally resolved PM2.5
      predictions and weighted monthly average concentrations of NO2 from up to five
      nearest monitors) and self-reported BMI using generalized additive models,
      allowing for deviations from linearity using penalized splines. RESULTS: Among
      23,435 women aged 60-87 years, we observed nonlinear associations between
      walkability and BMI and between PM2.5 and BMI in single-exposure models adjusted
      for age, race, and individual- and area-level socioeconomic status. When modeling
      all exposures simultaneously, only the association between walkability and BMI
      remained nonlinear and nonmonotonic. Increasing walkability was associated with
      increasing BMI at lower levels of walkability (walkability index <1.8), while
      increasing walkability was linked to lower BMI in areas of higher walkability
      (walkability index >1.8). A 10 percentile increase in walkability, right above
      1.8 was associated with a 0.84% decrease in log BMI. The relationship between
      walkability and BMI existed only among younger participants (<71 years old).
      CONCLUSIONS: Neighborhood walkability was nonlinearly linked to lower BMI
      independent of air pollution and greenness. Our findings highlight the importance
      of accounting for nonlinear confounding by interrelated urban environmental
      factors when investigating associations between the environment and BMI.

PMID- 28767515
TI  - Thirty-five-year Trends in First-time Hospitalization for Hip Fracture, 1-year
      Mortality, and the Prognostic Impact of Comorbidity: A Danish Nationwide Cohort
      Study, 1980-2014.
AB  - BACKGROUND: We examined trends in hip fracture incidence in Denmark from 1980 to
      2014, trends in subsequent 1-year mortality, and the prognostic impact of sex,
      age, and comorbidity. METHODS: This nationwide cohort study prospectively
      collected data from population-based Danish registries. We included 262,437
      patients with incident hip fracture and assessed comorbidity using the Charlson
      Comorbidity Index (CCI). RESULTS: Despite slight increases in incidence rates
      (IRs) of hip fracture up to the mid-1990s, the annual IR decreased by 29% from
      1980 to 2014 in women but remained stable in men. Decrease affected all age
      groups. IR decreased in patients without comorbidity but increased with
      increasing comorbidity (13% in patients with moderate and 510% in patients with
      very severe comorbidity). Adjusted mortality rate ratios (MRRs) following hip
      fracture in 2010-2014 compared with 1980-1984 were 0.68 (95% confidence interval
      [CI] = 0.65, 0.71) within 30 days and 0.63 (95% CI = 0.61, 0.66) within 31-365
      days. The mortality decreased up to 40% irrespective of comorbidity. Compared
      with patients with no comorbidity, those with very severe comorbidity had
      adjusted MRRs of 2.48 (95% CI = 2.39, 2.56) and 2.81 (95% CI = 2.74, 2.88) within
      30 days and 31-365 days post-hip fracture, respectively. CONCLUSIONS: Although
      the incidence rate of hip fracture increased substantially with increasing
      comorbidity, the following 1-year mortality decreased by 40% from 1980 through
      2014 irrespective of sex, age, and comorbidity level, suggesting improvement in
      both treatment and rehabilitation of patients with hip fracture. Comorbidity
      burden was, however, a strong prognostic factor for 1-year mortality after hip
      fracture.

PMID- 28767516
TI  - The "Residential" Effect Fallacy in Neighborhood and Health Studies: Formal
      Definition, Empirical Identification, and Correction.
AB  - BACKGROUND: Because of confounding from the urban/rural and socioeconomic
      organizations of territories and resulting correlation between residential and
      nonresidential exposures, classically estimated residential neighborhood-outcome
      associations capture nonresidential environment effects, overestimating
      residential intervention effects. Our study diagnosed and corrected this
      "residential" effect fallacy bias applicable to a large fraction of neighborhood
      and health studies. METHODS: Our empirical application investigated the effect
      that hypothetical interventions raising the residential number of services would
      have on the probability that a trip is walked. Using global positioning systems
      tracking and mobility surveys over 7 days (227 participants and 7440 trips), we
      employed a multilevel linear probability model to estimate the trip-level
      association between residential number of services and walking to derive a naive
      intervention effect estimate and a corrected model accounting for numbers of
      services at the residence, trip origin, and trip destination to determine a
      corrected intervention effect estimate (true effect conditional on assumptions).
      RESULTS: There was a strong correlation in service densities between the
      residential neighborhood and nonresidential places. From the naive model,
      hypothetical interventions raising the residential number of services to 200,
      500, and 1000 were associated with an increase by 0.020, 0.055, and 0.109 of the
      probability of walking in the intervention groups. Corrected estimates were of
      0.007, 0.019, and 0.039. Thus, naive estimates were overestimated by
      multiplicative factors of 3.0, 2.9, and 2.8. CONCLUSIONS: Commonly estimated
      residential intervention-outcome associations substantially overestimate true
      effects. Our somewhat paradoxical conclusion is that to estimate residential
      effects, investigators critically need information on nonresidential places
      visited.

PMID- 28767517
TI  - Accuracy of Self-reported Weight in Hispanic/Latino Adults of the Hispanic
      Community Health Study/Study of Latinos.
AB  - BACKGROUND: Previous US population-based studies have found that body weight may
      be underestimated when self-reported. However, this research may not apply to all
      US Hispanics/Latinos, many of whom are immigrants with distinct cultural
      orientations to ideal body size. We assessed the data quality and accuracy of
      self-reported weight in a diverse, community-based, US sample of primarily
      foreign-born Hispanic/Latino adults. METHODS: Using baseline data (2008-2011)
      from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we
      described the difference between contemporaneous self-reported and measured
      current body weight (n = 16,119) and used multivariate adjusted models to
      establish whether the observed trends in misreporting in potential predictors of
      inaccuracy persisted after adjustment for other predictors. Last, we described
      the weighted percentage agreement in body mass classification using either self
      reported or measured weight (n = 16,110). RESULTS: Self-reported weight was well
      correlated with (r = 0.95) and on average 0.23 kg greater than measured weight.
      The range of this misreporting was large and several factors were associated with
      misreporting: age group, gender, body mass categories, nativity, study site by
      background, unit of self-report (kg or lb), and end-digit preference. The
      percentage agreement of body mass classification using self-reported versus
      measured weight was 86% and varied across prevalent health conditions.
      CONCLUSIONS: The direction of misreporting in self-reported weight, and thus the
      anticipated bias in obesity prevalence estimates based on self-reported weights,
      may differ in US Hispanic/Latinos from that found in prior studies. Future
      investigations using self-reported body weight in US Hispanic/Latinos should
      consider this information for bias analyses.See video abstract at,
      http://links.lww.com/EDE/B276.

PMID- 28767518
TI  - Bayesian Model Averaging with Change Points to Assess the Impact of Vaccination
      and Public Health Interventions.
AB  - BACKGROUND: Pneumococcal conjugate vaccines (PCVs) prevent invasive pneumococcal
      disease and pneumonia. However, some low-and middle-income countries have yet to
      introduce PCV into their immunization programs due, in part, to lack of certainty
      about the potential impact. Assessing PCV benefits is challenging because
      specific data on pneumococcal disease are often lacking, and it can be difficult
      to separate the effects of factors other than the vaccine that could also affect
      pneumococcal disease rates. METHODS: We assess PCV impact by combining Bayesian
      model averaging with change-point models to estimate the timing and magnitude of
      vaccine-associated changes, while controlling for seasonality and other
      covariates. We applied our approach to monthly time series of age-stratified
      hospitalizations related to pneumococcal infection in children younger 5 years of
      age in the United States, Brazil, and Chile. RESULTS: Our method accurately
      detected changes in data in which we knew true and noteworthy changes occurred,
      i.e., in simulated data and for invasive pneumococcal disease. Moreover, 24
      months after the vaccine introduction, we detected reductions of 14%, 9%, and 9%
      in the United States, Brazil, and Chile, respectively, in all-cause pneumonia
      (ACP) hospitalizations for age group 0 to <1 years of age. CONCLUSIONS: Our
      approach provides a flexible and sensitive method to detect changes in disease
      incidence that occur after the introduction of a vaccine or other intervention,
      while avoiding biases that exist in current approaches to time-trend analyses.

PMID- 28767519
TI  - Is a Person's Place in the Home (Neighborhood)?

PMID- 28767521
TI  - Disabling Central Paroxysmal Positioning Upbeat Nystagmus and Vertigo Associated
      With the Presence of Anti-Glutamic Acid Decarboxylase Antibodies.
AB  - An immune attack by anti-glutamic acid decarboxylase (GAD) antibodies is believed
      to cause a deficiency in gamma-aminobutyric acid-mediated neurotransmission in
      the cerebellum. This, in turn, leads to several eye movement disorders, including
      spontaneous downbeat (DBN) and periodic alternating nystagmus. We describe a 68
      year-old diabetic woman with disabling paroxysmal positioning upbeat nystagmus
      (UBN) exclusively in the supine position, associated with asymptomatic
      spontaneous DBN, alternating skew deviation and hyperactive vestibulo-ocular
      reflex responses on head impulse testing, in whom high titers of anti-GAD
      antibodies were detected. After treatment with intravenous immunoglobulin, a
      complete resolution of positioning UBN and spontaneous DBN occurred, along with a
      decrease in anti-GAD antibody titers. Positioning UBN in this case may reflect a
      transient disinhibition of the central vestibular pathways carrying posterior
      semicircular canal signals, due to lack of normal inhibitory input from the
      cerebellar nodulus/uvula. Immunoglobulin restored cerebellar inhibitory output,
      possibly by improving gamma-aminobutyric acid neurotransmission.

PMID- 28767522
TI  - Effect of Physical Load on Aerobic Exercise Performance during Heat Stress.
AB  - PURPOSE: This study aimed to investigate the effect of increasing external loads
      on 5-km treadmill time trial (TT) performance in 20 degrees C and 40 degrees C
      environmental conditions and to construct an ecologically relevant performance
      prediction decision aid. METHODS: Twenty-six male and four female volunteers
      (age, 23.5 +/- 6.9 yr; weight, 76.0 +/- 8.9 kg; height, 1.75 +/- 0.07 m; VO2peak,
      50.7 +/- 4.5 mL.kg.min) participated in a counterbalanced, mixed-model design,
      with each subject assigned to a load group (20%, 30%, or 50% body mass (BM); n =
      10 per group). Volunteers performed three, self-paced 5-km familiarization TT
      (treadmill) without external load. Each volunteer then performed a 5-km TT in
      each environment with loads of either 20% (n = 10), 30% (n = 10), or 50% (n = 10)
      of BM. RESULTS: 1) Loads of (20%, 30%, and 50% of BM) impaired 5-km TT
      performance compared with that when unloaded (P < 0.05); 2) the time penalties of
      the 20% and 30% load were <50% load (P < 0.05); 3) in all trials, the addition of
      heat exposure reduced 5-km TT performance beyond the penalty of load itself (P <
      0.05); and 4) the combination of heat and 50% load resulted in a substantial
      penalty such that continuous work was not sustainable for all of the volunteers.
      CONCLUSIONS: Relative to prediction models using fixed or constant workload
      exercise trials, an ecologically valid decision aid was developed from self-paced
      data, in which pace (km.h) can be predicted for individual levels of heat, load,
      or heat + load in combination.

PMID- 28767523
TI  - Respiratory Mechanical and Cardiorespiratory Consequences of Cycling with
      Aerobars.
AB  - PURPOSE: Aerobars place a cyclist in a position where the trunk is flexed forward
      and the elbows are close to the midline of the body. This position is known to
      improve cycling aerodynamics and time trial race performance compared with
      upright cycling positions. However, the aggressive nature of this position may
      have important cardiorespiratory and metabolic consequences. The purpose of this
      investigation was to examine the respiratory mechanical, ventilatory, metabolic,
      and sensory consequences of cycling while using aerobars during laboratory-based
      cycling. METHODS: Eleven endurance-trained male cyclists (age, 26 +/- 9 yr;
      VO2peak, 55 +/- 5 mL.kg.min) were recruited. Visit 1 consisted of an incremental
      cycling test to determine peak power output. Visit 2 consisted of 6-min bouts of
      constant load cycling at 70% of peak incremental power output in the aerobar
      position, drop position, and upright position while grasping the brake hoods.
      Metabolic and ventilatory responses were measured using a commercially available
      metabolic cart, and respiratory pressures were measured using an esophageal
      catheter. RESULTS: Cycling in the aerobar position significantly increased the
      work of breathing (Wb), power of breathing (Pb), minute ventilation, ventilatory
      equivalent for oxygen and carbon dioxide, and transdiaphragmatic pressure
      compared with the upright position. Increases in the Wb and Pb in the aerobars
      relative to the upright position were strongly correlated with the degree of
      thoracic restriction, measured as the shoulder-to-aerobar width ratio (Wb: r =
      0.80, P = 0.01; Pb: r = 0.69, P = 0.04). CONCLUSIONS: Aerobars significantly
      increase the mechanical cost of breathing and leads to greater ventilatory
      inefficiency compared with upright cycling. Future work is needed to optimize
      aerobar width to minimize the respiratory mechanical consequences while
      optimizing aerodynamics.

PMID- 28767524
TI  - Endurance Exercise Attenuates Postprandial Whole-Body Leucine Balance in Trained
      Men.
AB  - PURPOSE: Endurance exercise increases indices of small intestinal damage and
      leucine oxidation, which may attenuate dietary amino acid appearance and
      postprandial leucine balance during postexercise recovery. Therefore, the purpose
      of this study was to examine the effect of an acute bout of endurance exercise on
      postprandial leucine kinetics and net leucine balance. METHODS: In a crossover
      design, seven trained young men (age = 25.6 +/- 2.3 yr; VO2peak = 61.4 +/- 2.9
      mL.kg.min; mean +/- SEM) received a primed constant infusion of L-[1-C]leucine
      before and after ingesting a mixed macronutrient meal containing 18 g whole egg
      protein intrinsically labeled with L-[5,5,5-H3]leucine, 17 g fat, and 60 g
      carbohydrate at rest and after 60 min of treadmill running at 70% VO2peak.
      RESULTS: Plasma intestinal fatty acid binding protein concentrations and leucine
      oxidation both increased (P < 0.01) to peaks that were ~2.5-fold above baseline
      values during exercise with a concomitant decrease (P < 0.01) in nonoxidative
      leucine disposal. Meal ingestion attenuated (P < 0.01) endogenous leucine rates
      of appearance at rest and after exercise. There were no differences (both, P >
      0.05) in dietary leucine appearance rates or in the amount of dietary protein
      derived leucine that appeared into circulation over the 5-h postprandial period
      at rest and after exercise (62% +/- 2% and 63% +/- 2%, respectively). Leucine
      balance over the 5-h postprandial period was positive (P < 0.01) in both
      conditions but was negative (P < 0.01) during the exercise trial after accounting
      for exercise-induced leucine oxidation. CONCLUSIONS: We demonstrate that
      endurance exercise does not modulate dietary leucine availability from a mixed
      meal but attenuates postprandial whole-body leucine balance in trained young men.

PMID- 28767525
TI  - Comparison of Lower Limb and Back Exercises for Runners with Chronic Low Back
      Pain.
AB  - INTRODUCTION: This single-blind randomized trial was conducted to compare the
      treatment effect of lower limb (LL) exercises versus conventional lumbar extensor
      (LE) and lumbar stabilization (LS) exercises in recreational runners with chronic
      low back pain (cLBP), because there is currently no specific protocol for
      managing runners with cLBP. METHODS: Eighty-four recreational runners with cLBP
      were allocated to three exercise groups (LL, LE, LS) for an 8-wk intervention.
      Outcome measures included self-rated pain and running capability, LL strength,
      back muscle function, and running gait. Participants were assessed at
      preintervention, mid-intervention, and end-intervention; selected outcomes also
      followed up at 3 and 6 months. Generalized estimating equation was adopted to
      examine group-time interaction. RESULTS: The LL group improved 0.949 points per
      time point in Patient-Specific Functional Scale (P < 0.001), which was higher
      than the LE (B = -0.198, P = 0.001) and LS groups (B = -0.263, P < 0.001). All
      three groups improved on average 0.746 points per time point in Numeric Pain
      Rating Scale for running-induced pain (P < 0.001). Knee extension strength
      increased 0.260 N.m.kg per time point (P < 0.001) in the LL group, which was
      higher than the LE (B = -0.220, P < 0.001) and LS groups (B = -0.206, P < 0.001).
      The LL group also showed a greater increase in running step length (2.464 cm per
      time point, P = 0.001) compared with LS group (B = -2.213, P = 0.013). All three
      groups improved similarly in back muscle function. CONCLUSION: LL exercise
      therapy could be a new option for cLPB management given its superior effects in
      improving running capability, knee extension strength, and running gait.

PMID- 28767526
TI  - Exercise Protects Skeletal Muscle during Chronic Doxorubicin Administration.
AB  - PURPOSE: This study aimed to assess the ability for exercise training performed
      before and during biweekly doxorubicin (DOX) administration to attenuate adverse
      effects of DOX on skeletal muscle. We hypothesized that DOX treatment would
      increase REDD1, impair mammalian target of rapamycin (mTOR) signaling, and reduce
      muscle fiber size, and that exercise training would attenuate these responses.
      METHODS: Eight-week-old ovariectomized female Sprague-Dawley rats were randomized
      to one of four treatments: exercise + DOX (Ex-Dox), Ex + vehicle (Ex-Veh),
      sedentary + DOX (Sed-Dox), and Sed + Veh (Sed-Veh). DOX (4 mg.kg) or vehicle
      (saline) intraperitoneal injections were performed biweekly for a total of three
      injections (cumulative dose, 12 mg.kg). Ex animals performed interval exercise (4
      * 4 min, 85%-90% VO2peak) 5 d.wk starting 1 wk before the first injection and
      continued throughout study duration. Animals were euthanized ~5 d after the last
      injection, during which the soleus muscle was dissected and prepared for
      immunoblot and immunohistochemical analyses. RESULTS: REDD1 mRNA and protein were
      increased only in Sed-Dox (P < 0.05). The phosphorylation of mTOR and 4E-BP1 and
      MHC I and MHC IIa fiber size were lower in Sed-Dox versus Sed-Veh (P < 0.05). By
      contrast, REDD1 mRNA and protein, mTOR, 4E-BP1, and MHC I fiber size were not
      different between Ex-Dox and Ex-Veh (P > 0.05). LC3BI was higher, and the
      LC3BII/I ratio was lower in Sed-Dox versus Sed-Veh (P < 0.05) but not between Ex
      Dox and Ex-Veh (P > 0.05). CONCLUSION: These data suggest that DOX may inhibit
      mTORC1 activity and reduce MHCI and MHCIIa fiber size, potentially through
      elevated REDD1, and that exercise may provide a therapeutic strategy to preserve
      skeletal muscle size during chronic DOX treatment.

PMID- 28767527
TI  - Bioenergetics and ATP Synthesis during Exercise: Role of Group III/IV Muscle
      Afferents.
AB  - PURPOSE: The purpose of this study was to investigate the role of the group
      III/IV muscle afferents in the bioenergetics of exercising skeletal muscle beyond
      constraining the magnitude of metabolic perturbation. METHODS: Eight healthy men
      performed intermittent isometric knee-extensor exercise to task failure at ~58%
      maximal voluntary contraction under control conditions (CTRL) and with lumbar
      intrathecal fentanyl to attenuate group III/IV leg muscle afferents (FENT).
      Intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi),
      diprotonated phosphate (H2PO4), adenosine triphosphate (ATP), and pH were
      determined using phosphorous magnetic resonance spectroscopy (P-MRS). RESULTS:
      The magnitude of metabolic perturbation was significantly greater in FENT
      compared with CTRL for [Pi] (37.8 +/- 16.8 vs 28.6 +/- 8.6 mM), [H2PO4] (24.3 +/-
      12.2 vs 17.9 +/- 7.1 mM), and [ATP] (75.8% +/- 17.5% vs 81.9% +/- 15.8% of
      baseline), whereas there was no significant difference in [PCr] (4.5 +/- 2.4 vs
      4.4 +/- 2.3 mM) or pH (6.51 +/- 0.10 vs 6.54 +/- 0.14). The rate of perturbation
      in [PCr], [Pi], [H2PO4], and pH was significantly faster in FENT compared with
      CTRL. Oxidative ATP synthesis was not significantly different between conditions.
      However, anaerobic ATP synthesis, through augmented creatine kinase and
      glycolysis reactions, was significantly greater in FENT than in CTRL, resulting
      in a significantly greater ATP cost of contraction (0.049 +/- 0.016 vs 0.038 +/-
      0.010 mM.min.N). CONCLUSION: Group III/IV muscle afferents not only constrain the
      magnitude of perturbation in intramuscular Pi, H2PO4, and ATP during small muscle
      mass exercise but also seem to play a role in maintaining efficient skeletal
      muscle contractile function in men.

PMID- 28767528
TI  - Should Benzodiazepines and Anticonvulsants Be Used During Electroconvulsive
      Therapy?: A Case Study and Literature Review.
AB  - OBJECTIVE: This study aims to investigate the clinical effects of benzodiazepines
      or anticonvulsant use during a course of electroconvulsive therapy (ECT). METHOD:
      A case report study of a patient who received ECT with and without concomitant
      flurazepam and pregabalin is presented. The literature on the use of
      benzodiazepines and anticonvulsants during ECT is reviewed. RESULTS: A woman with
      treatment resistant depression received a course of ECT while taking flurazepam
      and pregabalin, but seizures were of short duration and symptomatic improvement
      was minimal. After discontinuation of flurazepam and pregabalin, a course of
      right unilateral ultrabrief ECT was associated with adequate seizures and
      remission of depression and suicidal ideation. Our literature review suggests
      that benzodiazepines decrease seizure duration, but most evidence shows no
      association with increased seizure threshold. One prospective RCT and 3 large
      retrospective studies found that benzodiazepines compromise the efficacy of
      unilateral but not bilateral ECT. Regarding anticonvulsants, several studies had
      varied and contradictory results on their effect on seizure duration and seizure
      threshold. Of the 2 large retrospective studies and 3 RCTs, only 1 retrospective
      study showed that anticonvulsants decrease the efficacy of ECT. CONCLUSIONS:
      Judicious assessment of all medications used in combination with ECT is
      recommended. Overall, published studies suggest that benzodiazepines and
      anticonvulsants impact the clinical outcomes of ECT less than what would be
      expected given their pharmacologic effects. However, there are significant gaps
      in the literature, including a lack of study on suprathreshold stimulation of
      right unilateral ECT and the possibility of a greater effect with higher
      medication doses.

PMID- 28767529
TI  - Bifrontal Electroconvulsive Therapy in a Patient With Subcallosal Cingulate Deep
      Brain Stimulation for Depression.

PMID- 28767530
TI  - The Use of Ultrabrief Left Unilateral Electroconvulsive Therapy in a Patient With
      Cerebral Aneurysms and Right-Sided Encephalomalacia and Stroke: A Case Report.

PMID- 28767531
TI  - Catatonia Misdiagnosed as Dementia.

PMID- 28767532
TI  - Cardiac Arrest Secondary to Lightning Strike: Case Report and Review of the
      Literature.
AB  - Lightning strike injuries, although less common than electrical injuries, have a
      higher morbidity rate because of critical alterations of the circulatory system,
      respiratory system, and central nervous system. Most lightning-related deaths
      occur immediately after injury because of arrhythmia or respiratory failure. We
      describe the case of a pediatric patient who experienced cardiorespiratory arrest
      secondary to a lightning strike, where the Advanced Cardiac Life Support and
      Basic Life Support chain of survival was well executed, leading to return of
      spontaneous circulation and intact neurological survival. We review the
      pathophysiology of lightning injuries, prognostic factors of favorable outcome
      after cardiac arrest, including bystander cardiopulmonary resuscitation,
      shockable rhythm, and automatic external defibrillator use, and the importance of
      temperature management after cardiac arrest.

PMID- 28767533
TI  - Gender Equity in Transplantation: A Report from the Women in Transplantation
      Workshop of The Transplantation Society of Australia and New Zealand.
AB  - The exponential growth of young talented women choosing science and medicine as
      their professional career over the past decade is substantial. Currently, more
      than half of the Australian medical doctoral graduates and early career
      researchers are comprised of women, but less than 20% of all academic
      professorial staff are women. The loss of female talent in the hierarchical
      ladder of Australian academia is a considerable waste of government investment,
      productivity, and scientific innovation. Gender disparity in the professional
      workforce composition is even more striking within the field of transplantation.
      Women are grossly underrepresented in leadership roles, with currently no female
      heads of unit in any of the Australian and New Zealand transplanting centers. At
      the same time, there is also gender segregation with a greater concentration of
      women in lower-status academic position compared with their male counterparts.
      Given the extent and magnitude of the disparity, the Women in Transplantation
      Committee, a subcommittee of The Transplantation Society of Australia and New
      Zealand established a workshop comprising 8 female clinicians/scientists in
      transplantation. The key objectives were to (i) identify potential gender equity
      issues within the transplantation workforce; (ii) devise and implement potential
      strategies and interventions to address some of these challenges at a societal
      level; (iii) set realistic and achievable goals to enhance and facility gender
      equality, equity, and diversity in transplantation.

PMID- 28767534
TI  - A Cost Comparison for Telehealth Utilization in the Kidney Transplant Waitlist
      Evaluation Process.
AB  - BACKGROUND: There have been limited publications on telehealth utilization in
      transplantation with no prior reports of telehealth-related costs for
      pretransplant evaluations. The aim of this study is to compare costs throughout
      the evaluation process for those patients assessed initially by telehealth with
      those seen in-person. METHODS: All patients approved for kidney transplant
      waitlist evaluation at our center from March 2013 thru May 2016 with decisions
      were included in this study. Patients approved for evaluation were scheduled for
      either an initial telehealth or in-person visit, partly based on patient factors.
      Clinically related and travel-related costs were calculated. Time estimates for
      patient time needed to complete visit, time from application approval to initial
      visit, and time from application approval to decision were obtained. Comparisons
      were made using t tests. RESULTS: Thirty-nine months were included for 302
      patients. All categories of clinically or travel-related costs were significantly
      less for the telehealth cohort (P < 0.0001). Total mean cost per patient was US
      $656.11 versus US $1108.91 for the cohort initially evaluated by telehealth
      versus in-person (P < 0.001). The time needed to complete an evaluation (1.7 vs
      2.4 days, P < 0.001) and the time to initial evaluation (51.4 vs 87.9.0 days, P <
      0.001) were significantly less in the telehealth cohort. The cohort seen by
      telehealth was older with increased comorbidities (<0.001). CONCLUSIONS: As
      telemedicine applications continue to proliferate, we present our experience with
      telehealth for initial kidney transplant waitlist evaluations with associated
      reductions in cost and time which may also improve access to transplantation.

PMID- 28767535
TI  - Refractory Vascular Rejection in a Hand Allograft in the Presence of Antibodies
      Against Angiotensin II (Type 1) Receptor.

PMID- 28767537
TI  - Addressing Stigma in Medication Treatment of Adolescents With Opioid Use
      Disorder.
AB  - : In September 2016, the American Academic of Pediatrics released a policy
      statement that adolescents with opioid use disorder should be offered
      pharmacotherapy with buprenorphine/naloxone, methadone, or naltrexone. In our
      clinical practice, however, we have encountered the perception among patients,
      families, and clinicians alike that medications should be used as a last resort.
      That we should wait until things get worse is a discarded approach. As addiction
      specialists, it is imperative that we prevent and identify risky use and use
      disorders, then intervene early and offer timely, evidence-based treatment. We
      suggest that adolescents deserve special attention and that specific efforts
      should be made to reduce the stigma associated with treating adolescents with
      opioid use disorder with medications to optimize those efforts.

PMID- 28767536
TI  - Risk Factors Associated With Skin and Soft Tissue Infections Among Hospitalized
      People Who Inject Drugs.
AB  - OBJECTIVES: Skin and soft tissue infections (SSTIs) are common among people who
      inject drugs (PWID), and can lead to serious morbidity and costly emergency room
      and hospital utilization. A range of high-risk injection practices may contribute
      to these infections. The goal of the current study was to examine risk practices
      that were associated with SSTIs in a sample of hospitalized PWID. METHODS: PWID
      (N = 143; 40.6% female) were recruited from inpatient medical units at a large
      urban hospital and completed a baseline interview that focused on infection risk.
      Measures included demographics, substances used/injected, and self-report of
      SSTIs (ie, abscesses, ulcers, or cellulitis) within the past year. The Bacterial
      Infections Risk Scale for Injectors-a 7-item index-assessed specific behaviors
      expected to increase the risk of acquiring SSTIs (eg, injection without skin
      cleaning, intramuscular injection). RESULTS: The sample was 58% Caucasian and
      averaged 38.7 (SD = 10.7) years of age. Ninety-three participants (65%) reported
      at least 1 SSTI within the past year. Using a logistic regression model, the
      Bacterial Infections Risk Scale for Injectors (odds ratio 1.87, P = 0.004) and
      total number of injections over the past 3 months (odds ratio 2.21, P = 0.002)
      were associated with past year SSTIs. CONCLUSIONS: In conclusion, rates of past
      year SSTIs were high in this sample of hospitalized PWID. Results suggest that
      interventions should target specific injection practices to reduce infection
      risk.

PMID- 28767538
TI  - Two Fatal Intoxications Due to Tramadol Alone: Autopsy Case Reports and Review of
      the Literature.
AB  - Since tramadol was marketed, it has been widely prescribed as a pain killer
      because of its relatively safe profile among opioids.Nevertheless, intoxication
      can occur: overdose can lead to fatal outcomes mostly in association with other
      drugs, via the potential interaction with serotonergic antidepressant
      medications, as well as the potential for increased central nervous system (CNS)
      depression.Fatal outcomes only attributable to tramadol are a rare entity. In
      this case report, 2 fatal cases are described due to tramadol stand-alone
      intoxication with peculiar characteristics.In case 1, gas chromatography - mass
      spectrometry analysis detected tramadol in all specimens (32 MUg/mL in the heart
      blood, 23.9 MUg/mL in the femoral blood, 3.3 MUg/mL in the bile, and 1.4 MUg/mL
      in the urine). No other CNS depressants were detected by toxicological
      analysis.In case 2, gas chromatography - mass spectrometry analysis detected
      tramadol in all specimens (7.5 MUg/mL in the heart blood, 5.8 MUg/mL in the
      femoral blood, and 18 MUg/mL in the urine). No other CNS depressants were
      detected by toxicological analysis.Review of the literature was performed to
      clarify the actual knowledge on this topic.

PMID- 28767539
TI  - Medicolegal Investigations Into Deaths Due to Crush Asphyxia After Tractor Side
      Rollovers.
AB  - Farm tractors are large, heavy, powerful vehicles with a high center of gravity.
      When driven carelessly on sloping, irregular, or slippery ground, tractors can
      overturn sideways and cause the death by crush asphyxia of the driver or
      passengers, especially if appropriate safety equipment is not fitted or used. The
      aim of this review is to focus on the diagnostic difficulties with which coroners
      and forensic pathologists have to cope when a confirmation of crush asphyxia
      after tractor side rollover is required by judicial authorities. Forensic
      investigations in such cases must involve the meticulous analysis of the death
      scene and the mechanical characteristics of the vehicle together with accurate
      postmortem and toxicological examination.

PMID- 28767540
TI  - Interprofessional Competency Toolkit for Internationally Educated Health
      Professionals: Evaluation and Pilot Testing.
AB  - INTRODUCTION: Internationally Educated Health Professionals (IEHPs) constitute a
      major health care workforce in Canada. Interprofessional education is
      particularly important for IEHPs to integrate into the Canadian health care
      system. We designed an online interprofessional education curriculum for IEHPs.
      The curriculum is designed to cover the six interprofessional competency domains
      defined in the Canadian Interprofessional Health Collaborative National
      Interprofessional Competency Framework. In this article, we are presenting
      findings from the pilot testing of the curriculum with a cohort of IEHPs and
      educators. METHODS: We conducted surveys and interviews with IEHPs and educators
      from four provinces (British Columbia, Alberta, Saskatchewan, and Manitoba). We
      aimed to include seven healthcare professionals: licensed practical nurses,
      registered nurses, registered psychiatric nurses, pharmacists, physicians,
      occupational therapists, and physical therapists. We also used a pre- post- self
      assessment tool and a set of reflective questions to measure the effectiveness of
      the curriculum. RESULTS: Thirty IEHPs and five educators reviewed the online
      curriculum and participated in this evaluation. Postintervention confidence
      scores for all items under the role clarification and patient-centered care
      domains increased significantly (P = <0.01) after module completion. The scores
      also increased for most questions in team functioning, collaborative leadership,
      and communication domains. The postassessment scores increased for only half of
      the questions in conflict management domains. Participants agreed with the
      appropriateness of the content in terms of language, scenarios, and cultural
      aspects covered in the online curriculum on interprofessional education.
      DISCUSSION: The content of the curriculum improved IEHPs' understanding of
      interprofessional collaboration in Canada. The interprofessional curriculum is a
      creative and useful resource to improve collaborative practice among
      internationally educated health professionals in Canada.

PMID- 28767541
TI  - Relationships Between Reflection and Behavior Change in CME.
AB  - INTRODUCTION: Reflection exposes performance gaps and is a step in the process of
      behavior change among adult learners. However, little is known about the
      relationships between reflection and behavior change in CME. Our objectives were
      to measure associations between validated reflection scores and behavior change
      among CME participants and to identify associations between reflection and
      characteristics of CME presentations. METHODS: This was a cohort study of
      attendees at a national hospital medicine CME course. Participants provided
      reflection scores for each presentation and planned commitment-to-change (CTC)
      statements at the conclusion of the course. Reflection scores from 1 (strongly
      disagree) to 5 (strongly agree) were averaged for each presentation. CTC
      statements were linked to their accompanying presentations. A 3-month postcourse
      survey was conducted to assess if planned CTCs were successfully implemented.
      RESULTS: In all, 223 of 281 participants (79.4%) returned evaluations. Of the 195
      planned CTC statements available for postcourse analysis, 128 (65.6%) were
      implemented. Reflection scores correlated with the number of planned CTC
      statements across all presentations (Pearson correlation, 0.65; P < .001). In
      addition, higher reflection scores (mean [SD]) were associated with the presence
      of audience response opportunities (Yes: 4.13 [0.18] versus No: 3.96 [0.16]; P =
      .01) and the use of clinical cases (Yes: 4.09 [0.18] versus No: 3.86 [0.12]; P <
      .01). DISCUSSION: To our knowledge, this is the first study to show a
      relationship between participant reflection and CTC in conference-based CME.
      Presentations that incorporate clinical cases and audience response systems seem
      to stimulate participant reflection and behavior change.

PMID- 28767542
TI  - Factors Influencing Physicians' Selection of Continuous Professional Development
      Activities: A Cross-Specialty National Survey.
AB  - INTRODUCTION: We sought to understand what influences physicians' decisions about
      participation in continuous professional development (CPD) activities, and how
      often physicians engage in specific CPD activities. METHODS: From September 2015
      to April 2016, we administered a survey to 4648 randomly sampled licensed US
      physicians. Survey items addressed perceived barriers to CPD, factors that might
      influence participation in four prototypical CPD activities (reading an article,
      or completing a local activity, online course, or far-away course), and frequency
      of CPD engagement. RESULTS: Nine hundred eighty-eight (21.6%) physicians
      responded. The most important barriers were time (mean [SD] 3.5 [1.3], 1 = not
      important, 5 = extremely important) and cost (2.9 [1.3]). In prioritizing factors
      influencing participation in four prototypical CPD activities, topical relevance
      consistently had the highest average rank. Quality of content and time to
      complete the activity were also frequently selected. Over the past 3 years, most
      physicians reported having participated in patient-focused learning and self
      directed learning on a weekly basis; quality improvement and local continuing
      medical education (CME) activities several times per year; online learning, on
      site courses, and national board-related activities a few times per year; and
      interprofessional learning less than once per year. Physicians believed that they
      ought to engage more often in all of these activities except board-related
      activities. They would like CME credit for these activities much more often than
      currently obtained. DISCUSSION: The reasons physicians select a given CPD
      activity vary by activity, but invariably include topic and quality of content.
      Physicians want CME credit for the CPD activities they are already doing.

PMID- 28767544
TI  - Compensatory Reserve Index: Performance of A Novel Monitoring Technology to
      Identify the Bleeding Trauma Patient.
AB  - INTRODUCTION: Hemorrhage is one of the most substantial causes of death after
      traumatic injury. Standard measures, including systolic blood pressure (SBP), are
      poor surrogate indicators of physiologic compromise until compensatory mechanisms
      have been overwhelmed. Compensatory Reserve Index (CRI) is a novel monitoring
      technology with the ability to assess physiologic reserve. We hypothesized CRI
      would be a better predictor of physiologic compromise secondary to hemorrhage
      than traditional vital signs. METHODS: A prospective observational study of 89
      subjects meeting trauma center activation criteria at a single level I trauma
      center was conducted from October 2015 to February 2016. Data collected included
      demographics, SBP, heart rate, and requirement for hemorrhage-associated, life
      saving intervention (LSI) (i.e., operation or angiography for hemorrhage, local
      or tourniquet control of external bleeding, and transfusion >2 units PRBC).
      Receiver-operator characteristic (ROC) curves were formulated and appropriate
      thresholds were calculated to compare relative value of the metrics for
      predictive modeling. RESULTS: For predicting hemorrhage-related LSI, CRI
      demonstrated a sensitivity of 83% and a negative predictive value (NPV) of 91% as
      compared with SBP with a sensitivity to detect hemorrhage of 26% (P < 0.05) and
      an NPV of 78%. ROC curves generated from admission CRI and SBP measures
      demonstrated values of 0.83 and 0.62, respectively. CRI identified significant
      hemorrhage requiring potentially life-saving therapy more reliably than SBP (P <
      0.05). CONCLUSION: The CRI device demonstrated superior capacity over systolic
      blood pressure in predicting the need for posttraumatic hemorrhage intervention
      in the acute resuscitation phase after injury.

PMID- 28767543
TI  - Lactate and Immunosuppression in Sepsis.
AB  - Serum lactate levels are traditionally interpreted as a marker of tissue hypoxia
      and often used clinically as an indicator of severity and outcome of
      sepsis/septic shock. Interestingly, recent studies involving the effects of tumor
      derived lactate suggest that lactate itself may have an immunosuppressive effect
      in its local environment. This finding adds to the recent advances in
      immunometabolism that shed light on the importance of metabolism and metabolic
      intermediates in the regulation of innate immune and inflammatory responses in
      sepsis. In this article, we summarize recent studies, showing that the activation
      of immune cells requires aerobic glycolytic metabolism and that lactate produced
      by aerobic glycolysis may play an immunosuppressive role in sepsis.

PMID- 28767546
TI  - A Pilot Study of Horizontal Head and Eye Rotations in Baseball Batting.
AB  - PURPOSE: The purpose of the study was to measure and compare horizontal head and
      eye tracking movements as baseball batters "took" pitches and swung at baseball
      pitches. METHODS: Two former college baseball players were tested in two
      conditions. A pitching machine was used to project tennis balls toward the
      subjects. In the first condition, subjects acted as if they were taking (i.e.,
      not swinging) the pitches. In the second condition, subjects attempted to bat the
      pitched balls. Head movements were measured with an inertial sensor; eye
      movements were measured with a video eye tracker. RESULTS: For each condition,
      the relationship between the horizontal head and eye rotations was similar for
      the two subjects, as were the overall head-, eye-, and gaze-tracking strategies.
      In the "take" condition, head movements in the direction of the ball were larger
      than eye movements for much of the pitch trajectory. Large eye movements occurred
      only late in the pitch trajectory. Gaze was directed near the ball until
      approximately 150 milliseconds before the ball arrived at the batter, at which
      time gaze was directed ahead of the ball to a location near that occupied when
      the ball crosses the plate. In the "swing" condition, head movements in the
      direction of the ball were larger than eye movements throughout the pitch
      trajectory. Gaze was directed near the ball until approximately 50 to 60
      milliseconds prior to pitch arrival at the batter. DISCUSSION: Horizontal head
      rotations were larger than horizontal eye rotations in both the "take" and
      "swing" conditions. Gaze was directed ahead of the ball late in the pitch
      trajectory in the "take" condition, whereas gaze was directed near the ball
      throughout much of the pitch trajectory in the "swing" condition.

PMID- 28767547
TI  - Hand-assisted Approach as a Model to Teach Complex Laparoscopic Hepatectomies:
      Preliminary Results.
AB  - BACKGROUND: Currently, there are limited and scarce models to teach complex liver
      resections by laparoscopy. The aim of this study is to present a hand-assisted
      technique to teach complex laparoscopic hepatectomies for fellows in liver
      surgery. MATERIALS AND METHODS: Laparoscopic hand-assisted approach for
      resections of liver lesions located in posterosuperior segments (7, 6/7, 7/8, 8)
      was performed by the trainees with guidance and intermittent intervention of a
      senior surgeon. Data as: (1) percentage of time that the senior surgeon takes the
      surgery as main surgeon, (2) need for the senior surgeon to finish the procedure,
      (3) necessity of conversion, (4) bleeding with hemodynamic instability, (5) need
      for transfusion, (6) oncological surgical margins, were evaluated. RESULTS: In
      total, 12 cases of complex laparoscopic liver resections were performed by the
      trainee. All cases included deep lesions situated on liver segments 7 or 8. The
      senior surgeon intervention occurred in a mean of 20% of the total surgical time
      (range, 0% to 50%). A senior intervention >20% was necessary in 2 cases. There
      was no need for conversion or reoperation. Neither major bleeding nor
      complications resulted from the teaching program. All surgical margins were
      clear. CONCLUSIONS: This preliminary report shows that hand-assistance is a safe
      way to teach complex liver resections without compromising patient safety or
      oncological results. More cases are still necessary to draw definitive
      conclusions about this teaching method.

PMID- 28767548
TI  - The Balance Between Surgical Resident Education and Patient Safety in
      Laparoscopic Colorectal Surgery: Surgical Resident's Performance has No Negative
      Impact.
AB  - OBJECTIVE: This study aimed to evaluate the feasibility and effectiveness of a
      comprehensive theoretical and hands-on training program in performing
      laparoscopic colonic resections under supervision of an expert surgeon. MATERIALS
      AND METHODS: Laparoscopic right colectomy was performed in 78 patients (10 with
      benign disease, 68 with carcinoma). Demographic, intraoperative, pathologic
      examination, and short-term outcome data were retrospectively compared between 25
      patients operated by surgical residents (R group) and 53 patients operated by
      senior surgeons (S group). The residents who performed surgeries in the R group
      had between 1 and 6 years after graduation; no experience with open or
      laparoscopic colorectal surgery was necessary. The residents completed a training
      program under supervision of a single expert laparoscopic colorectal surgeon,
      which included 6 steps, from basic skills to certification. RESULTS: There were
      no differences in patient age, sex, and body mass index between the R and S
      groups. Significantly more patients in the R group had early cancer and benign
      lesions (P<0.05). Thirteen of the 16 residents (81.2 %) had not had prior
      experience with colonic resection. The time of suturing and knot tying in the dry
      box did not differ between residents and senior surgeons (68 and 69 s,
      respectively). All the residents performed laparoscopic right colectomy without
      intraoperative complications. There were no significant differences in operating
      time (R group: 173+/-34 min, S group: 172+/-52 min), mean estimated blood loss
      (50+/-111 vs. 49+/-100 mL), number of lymph nodes dissected (20.8+/-12.8 vs.
      17.1+/-9.0), and mean postoperative hospital stay (9.1+/-3.3 vs. 10.7+/-4.1 d).
      On the basis of the year of their residency period, all 3 residents at 6 years
      after graduation had far greater experience than the other residents and
      therefore performed the surgery with minor verbal support from the expert.
      However, residents with 1 or 2 years after graduation had to receive guidance
      provision by the expert during surgery. CONCLUSIONS: When supervised and led by
      an expert laparoscopic surgeon, surgical residents are capable of performing
      laparoscopic surgery without negative effects on outcomes.

PMID- 28767549
TI  - The Feasibility of Hand-assisted Laparoscopic and Laparoscopic Multivisceral
      Resection Compared With Open Surgery for Locally Advanced Colorectal Cancer.
AB  - BACKGROUND: The role of hand-assisted laparoscopic and pure laparoscopic surgery
      for locally advanced colorectal cancer invading or adhering to neighboring organs
      is controversial. This study evaluated the safety and feasibility of laparoscopic
      multivisceral resection for colorectal cancer. PATIENTS AND METHODS: This study
      included 201 patients who underwent multivisceral resection for locally advanced
      colorectal cancer from January 2007 to December 2013 in the Department of General
      Surgery, Henan Provincial Hospital. Perioperative outcomes and long-time outcomes
      were compared among hand-assisted laparoscopic, laparoscopic and open resections.
      RESULTS: Estimated blood loss, wound length, time to the first flatus, and
      postoperative hospital stay were significantly less or shorter in the hand
      assisted laparoscopic surgery (HALS) and laparoscopic surgery group than in open
      surgery (OS) group. There were no significant differences in tumor size,
      retrieved lymph nodes, and R0 resection rate of the primary tumor among the 3
      groups. Surgeries started as laparoscopic surgery were completed in that manner
      76.6% of the time with 10.6% being converted to OS and 12.8% converted to HALS
      and there were only 2 conversions (2.2%) to OS in the HALS group. No significant
      difference was noted for overall morbidity rate and reoperation rate among the 3
      groups. The overall observed 5-year survival rate was 60.5% in the laparoscopic
      group, 55.4% in the HALS group, and 47.7% in the open group. There was no
      significant difference among the 3 groups in the 5-year survival rate.
      CONCLUSIONS: Hand-assisted laparoscopic and pure laparoscopic multivisceral
      resection for locally advanced colorectal cancer is safe and feasible in selected
      patients. HALS can be used judiciously to reduce the rate of conversion to an
      open procedure and may be a better alternative for laparoscopic approach.

PMID- 28767550
TI  - IMPACT OF LONG-TERM INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR ON
      PREEXISTING MICROSTRUCTURAL ALTERATIONS IN DIABETIC MACULAR EDEMA.
AB  - PURPOSE: Evaluation of the influence of long-term intravitreal anti-vascular
      endothelial growth factor treatment on preexisting retinal microstructural
      alterations in patients with diabetic macular edema. METHODS: Eyes with diabetic
      macular edema and a history of >= 20 intravitreal anti-vascular endothelial
      growth factor (aflibercept and/or ranibizumab) injections were included in this
      retrospective study. Primary outcome was the extent of disorganization of retinal
      inner layers, alterations at the outer plexiform layer/Henle fiber layer
      junction, disruption of external limiting membrane/ellipsoid zone, disruption of
      retinal pigment epithelium/Bruch complex, and retinal atrophy at baseline versus
      after >= 20 intravitreal injections as visualized by spectral-domain optical
      coherence tomography images. RESULTS: Of 383 eyes screened, 37 eyes were included
      in the current study. With the exception of outer plexiform layer/Henle fiber
      layer junction restoration, no significant changes regarding microstructural
      alterations between baseline and end of study were encountered after long-term
      anti-vascular endothelial growth factor (disorganization of retinal inner layers
      P = 0.381, outer plexiform layer/Henle fiber layer junction P = 0.001, external
      limiting membrane/ellipsoid zone P = 0.524, retinal pigment epithelium/Bruch
      complex P = 0.122, retinal atrophy P = 0.317). Best-corrected visual acuity
      significantly increased over the course of the study, corresponding to central
      retinal thickness and intraretinal fluid reduction (all P < 0.0001). The extent
      of microstructural alterations was negatively correlated with best-corrected
      visual acuity (P < 0.05). CONCLUSION: Apart from outer plexiform layer/Henle
      fiber layer junction layer restoration, no effect on preexisting retinal
      alterations was encountered after long-term intravitreal injections. Thus,
      intravitreal ranibizumab or aflibercept did not have a major effect (neither
      positive nor negative) on microstructural alterations.

PMID- 28767551
TI  - OCRIPLASMIN FOR VITREOMACULAR TRACTION: LOOKING OUTSIDE THE MACULA: A Wide-Field
      Optical Coherence Tomography Study.
AB  - PURPOSE: To evaluate baseline features and morphologic changes of vitreoretinal
      adhesion and outer retinal layers outside the macula after intravitreal
      ocriplasmin injection. To study the relation between vitreous detachment and
      attenuation of retinal outer segments signal. METHODS: Retrospective cases series
      of 15 eyes. Each eye was scanned with the 55 degrees  wide-field optical
      coherence tomography lens in 6 different locations, three horizontal B-scan
      (central, temporal, and nasal) and three vertical B-scan (central, superior, and
      inferior) at baseline, 1 week, 1 month, 3 months, and 6 months after injection.
      RESULTS: After ocriplasmin injection, vitreomacular traction (VMT) resolved in 12
      patients (80%), 3 of them presenting a complete posterior vitreous detachment.
      Eight patients (53%) showed a panretinal attenuation of photoreceptors outer
      segment signal, 7 with VMT resolution and 1 with non-posterior vitreous
      detachment and no VMT resolution. In three patients after VMT resolution the
      attenuation involved also areas with no posterior vitreous detachment. The
      attenuation resolved during follow-up in 7/8 eyes (87.5%). CONCLUSION:
      Intravitreal ocriplasmin injection induced resolution of VMT in most cases and
      more rarely a release of vitreopapillary adhesion and a complete posterior
      vitreous detachment. An acute panretinopathy was visible in more than half of the
      patients and was not related to vitreous detachment.

PMID- 28767552
TI  - EFFICACY AND FREQUENCY OF INTRAVITREAL AFLIBERCEPT VERSUS BEVACIZUMAB FOR MACULAR
      EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION.
AB  - PURPOSE: To compare the safety, efficacy, and frequency of intravitreal injection
      of aflibercept and bevacizumab for treatment of macular edema secondary to
      central retinal vein occlusion. DESIGN: Prospective, comparative, randomized,
      interventional study. PATIENTS AND METHODS: Eyes with macular edema secondary to
      central retinal vein occlusion were randomized between two groups according to
      the intravitreal injection used. Group A included eyes treated with intravitreal
      aflibercept, and Group B included eyes treated with intravitreal bevacizumab
      injections. The inclusion criteria were macular edema secondary to central
      retinal vein occlusion and follow-up duration of at least 12 months after the
      first injection. Exclusion criteria were macular ischemia, associated diabetes,
      hypertensive or renal retinopathy, other retinal disease, and previous anti
      vascular endothelial growth factor injection. The main outcome measures are
      central foveal thickness, best-corrected visual acuity, time intervals between
      injections, improved retinal nonperfusion, and any reported complication.
      RESULTS: Group A included 39 patients with a mean age of 57.4 +/- 8.2 years.
      Group B included 40 eyes with a mean age of 56.5 +/- 9.1 years. Twelve months
      after the first injection, central foveal thickness significantly improved from
      475.45 +/- 71.05 m to 259.11 +/- 20.67 m in Group A and from 460.22 +/- 89.38 m
      to 264.29 +/- 32.05 m in Group B; best-corrected visual acuity significantly
      improved from 0.81 +/- 0.16 logarithm of the minimum angle of resolution (20/125)
      to 0.34 +/- 0.14 logarithm of the minimum angle of resolution (20/40) in Group A
      and from 0.73 +/- 0.15 logarithm of the minimum angle of resolution (20/100) to
      0.33 +/- 0.17 logarithm of the minimum angle of resolution (20/40) in Group B;
      the mean number of injections was 3.72 +/- 2.93 in Group A and was 5.44 +/- 2.85
      in Group B (P < 0.05); and the mean interval between injections was 54.23 +/-
      8.47 days in Group A and was 35.12 +/- 7.76 days in Group B (P < 0.05). Retinal
      nonperfusion improved in 9/12 eyes in Group A and in 3/8 eyes in Group B (P <
      0.05). CONCLUSION: Both aflibercept and bevacizumab are comparably effective for
      treatment of macular edema secondary to central retinal vein occlusion without
      significant complications. However, the burden of frequent intravitreal
      injections could be significantly reduced when using aflibercept.

PMID- 28767553
TI  - TEMPORAL VASCULAR ARCADE WIDTH AND ANGLE IN HIGH AXIAL MYOPIA.
AB  - PURPOSE: Axial myopia is associated with elongation of the posterior ocular
      segment. The authors measured posterior fundus landmarks and assessed their
      associations with axial length. METHODS: Using fundus photographs, the authors
      measured the vertical distance between the temporal superior and temporal
      inferior arterial arcade (VDA) and the angle kappa between the temporal arterial
      arcades among other morphometric variables. RESULTS: The study included 456 eyes
      with a mean age of 61.2 +/- 14.2 years (range: 13-88 years) and mean axial length
      of 29.4 +/- 2.1 mm (range: 23.2-35.3 mm). Mean angle kappa was 91.3 +/- 17.2
      degrees  (range: 39-161 degrees ), and mean VDA was 7.93 +/- 1.71 mm (range: 2.72
      12.85 mm). In multivariate regression analysis, wider angle kappa was associated
      (regression coefficient r: 0.47) with shorter axial length (P = 0.002; beta: 
      0.17; B: -1.37; 95% confidence interval [CI]:-2.23 to -0.51), longer VDA (P <
      0.001; beta: 0.27; B: 2.70; 95% CI: 1.85-3.54), shorter disk-foveola distance (P
      < 0.001; beta: -0.22; B: -4.76; 95% CI: -7.05 to -2.46), shorter vertical optic
      disk diameter (P = 0.002; beta: -0.14; B: -6.83; 95% CI: -11.1 to -2.56), lower
      number of any chorioretinal lesions (P = 0.007; beta: -0.13; B: -2.11; 95% CI: 
      3.63 to -0.58), and longer maximal vertical chorioretinal lesion diameter (P =
      0.05; beta: 0.09; B: 0.92; 95% CI: -0.02 to 1.86). A longer VDA was associated
      (r: 0.31) with longer axial length (P < 0.001; beta: 0.22; B: 0.18; 95% CI: 0.10
      0.25), wider angle kappa (P < 0.001; beta: 0.28; B: 0.03; 95% CI: 0.02-0.04) and
      higher number of chorioretinal lesions (P = 0.03; beta: 0.10; B: 0.16; 95% CI:
      0.02-0.31). If eyes with chorioretinal lesions were excluded, the association
      between longer VDA and longer axial length was no longer statistically
      significant (P > 0.10). CONCLUSION: Axial elongation was correlated with
      decreasing angle kappa, caused by an elongation of the disk-foveola distance
      because of an enlargement of the gamma zone, whereas VDA remained constant. By
      contrast, horizontal length of macular Bruch membrane and vertical length of
      macular Bruch membrane were independent of axial elongation. Axial elongation did
      not lead to lengthening of Bruch membrane in the macular region in eyes without
      macular chorioretinal lesions.

PMID- 28767555
TI  - FOVEAL AVASCULAR ZONE AREA AFTER INTERNAL LIMITING MEMBRANE PEELING FOR
      EPIRETINAL MEMBRANE AND MACULAR HOLE COMPARED WITH THAT OF FELLOW EYES AND
      HEALTHY CONTROLS.
AB  - PURPOSE: To measure the foveal avascular zone (FAZ) area after internal limiting
      membrane (ILM) peeling and to determine the factors significantly correlated with
      the FAZ area. METHODS: This was a retrospective, observational, and cross
      sectional study. The affected and normal fellow eyes of 102 patients with
      unilateral macular diseases and 169 healthy subjects were studied. The patients
      underwent successful vitrectomy with internal limiting membrane peeling for an
      epiretinal membrane (n = 56) or a macular hole (n = 46). The superficial FAZ area
      and average foveal (within 1 mm) thickness were measured. The main outcome
      measures were the en face FAZ area measured in the optical coherence tomography
      angiographic images. RESULTS: The FAZ area in the epiretinal membrane group
      (0.148 +/- 0.094 mm) and in the macular hole group (0.255 +/- 0.111 mm) were
      significantly smaller than that in the healthy control group (0.358 +/- 0.118 mm;
      all, P < 0.0001). Multiple regression analysis showed that a thicker fovea was
      significantly correlated with a smaller FAZ area in the epiretinal membrane group
      (r = -0.799, P < 0.0001), macular hole group (r = -0.473, P = 0.0042), and
      control group (r = -0.612, P < 0.0001). CONCLUSION: The FAZ area after internal
      limiting membrane peeling was smaller than that of the controls. A smaller FAZ
      area was correlated with a thicker fovea both in internal limiting membrane
      peeled eyes and normal eyes.

PMID- 28767556
TI  - Correspondence.

PMID- 28767554
TI  - COMPARISON OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHIC CHANGES AFTER ANTI
      VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY ALONE OR IN COMBINATION WITH
      PHOTODYNAMIC THERAPY IN POLYPOIDAL CHOROIDAL VASCULOPATHY.
AB  - PURPOSE: To compare changes in optical coherence tomography angiography in eyes
      with polypoidal choroidal vasculopathy after treatment with anti-vascular
      endothelial growth factor monotherapy or combined with photodynamic therapy.
      METHODS: This is a longitudinal case-controlled study. The authors performed
      optical coherence tomography angiography at baseline and Month 3 in patients with
      treatment-naive polypoidal choroidal vasculopathy undergoing monotherapy (n = 10)
      or combination therapy (n = 13). We analyzed flow signal within the outer retina
      and choriocapillaris using automated segmentation. The authors analyzed the
      presence of pachyvessels using a 10.4-MUm segment through Haller layer. The
      changes in each layer were compared between treatments. RESULTS: At Month 3, both
      groups showed similar improvement in best-corrected visual acuity and central
      retinal thickness. However, flow signal within the polypoidal choroidal
      vasculopathy complex was decreased in more eyes after combination therapy than
      after monotherapy (84.6% vs. 40.0%, P = 0.04). Patchy reduction in flow signal
      within the choriocapillaris layer was noted in 15.4% and 10.0% after combination
      therapy and monotherapy, respectively (P = 0.61). Significant reduction in
      pachyvessel caliber was seen only after combination therapy but not after
      monotherapy (75.0% vs. 0.0%, P = 0.01). CONCLUSION: Longitudinal optical
      coherence tomography angiography demonstrates more significant reduction in
      lesion flow and pachyvessels in the short term after combination therapy than
      after monotherapy, although visual and structural OCT showed similar improvement.

PMID- 28767557
TI  - Reply.

PMID- 28767558
TI  - Liver Function in Patients With Nonalcoholic Fatty Liver Disease Randomized to
      Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: A Secondary Analysis of a
      Randomized Clinical Trial.
AB  - OBJECTIVES: The aim of the study was to compare the influence of sleeve
      gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB) on liver function in
      bariatric patients with non-alcoholic fatty liver disease (NAFLD) in a randomized
      clinical trial (NCT01806506). BACKGROUND: Rapid weight loss and malabsorption
      after bariatric surgery in patients with NAFLD or steatohepatitis (NASH) may
      impair liver function. METHODS: Sixty-six morbidly obese patients randomized to
      SG or RYGB were included in a secondary outcome analysis. Intraoperative liver
      biopsies were categorized with NAFLD Activity Score (NAS) and liver function
      tests were done before surgery and after 1, 6 and 12 months. RESULTS: NASH was
      present in 54.5% RYGB and 51.5% SG patients (P > 0.05). At 12 months excess
      weight loss was 68.7 +/- 19.7% after SG and 62.8 +/- 18.5% after RYGB (P > 0.05).
      At 1 month international normalized ratio (INR) increased after RYGB (0.98 +/-
      0.05 vs 1.14 +/- 0.11; P < 0.05) and SG (0.99 +/- 0.06 vs 1.04 +/- 0.06; P <
      0.05), RYGB induced significantly greater increase in INR in the whole group and
      NASH patients than SG. After RYGB albumin decreased at 1 month (41.2 +/- 2.7 vs
      39.0 +/- 3.2 g/L; P < 0.05). At 12 months, INR and albumin returned to baseline.
      At 12 months in NASH group, SG induced significant improvement in aspartate
      aminotransferase (32.4 +/- 17.4 vs 21.5 +/- 6.9U/L), alanine aminotransferase
      (39.9 +/- 28.6U/L vs 23.8 +/- 14.1U/L), gamma-glutamyl transpeptidase (34.3 +/-
      16.6 vs 24.5 +/- 16.8U/L), and lactate dehydrogenase (510.8 +/- 33 vs 292.4 +/-
      29). Variables predictive of INR change after 1 month included operation type,
      NAS >= 5, bilirubin, body mass index, hemoglobin A1C, and dyslipidemia.
      CONCLUSIONS: Patients with NASH undergoing RYGB are more susceptible to early
      transient deterioration of liver function than after SG.

PMID- 28767559
TI  - How Do We Value Postoperative Recovery?: A Systematic Review of the Measurement
      Properties of Patient-reported Outcomes After Abdominal Surgery.
AB  - OBJECTIVE: To appraise the level of evidence supporting the measurement
      properties of patient-reported outcome measures (PROMs) in the context of
      postoperative recovery after abdominal surgery. BACKGROUND: There is growing
      interest in using PROMs to support value-based care in abdominal surgery;
      however, to draw valid conclusions regarding patient-reported outcomes data,
      PROMs with robust measurement properties are required. METHODS: Eight databases
      (MEDLINE, EMBASE, Biosis, PsycINFO, The Cochrane Library, CINAHL, Scopus, Web of
      Science) were searched for studies focused on the measurement properties of PROMs
      in the context of recovery after abdominal surgery. The methodological quality of
      individual studies was evaluated using the consensus-based COSMIN checklist.
      Evidence supporting the measurement properties of each PROM was synthetized
      according to standardized criteria and compared against the International Society
      of Quality of Life Research minimum standards for the selection of PROMs for
      outcomes research. RESULTS: We identified 35 studies evaluating 22 PROMs [12
      focused on nonspecific surgical populations (55%), 4 focused on abdominal surgery
      (18%), and 6 generic PROMs (27%)]. The great majority of the studies (74%)
      received only poor or fair quality ratings. Measurement properties of PROMs were
      predominantly supported by limited or unknown evidence. None of the PROMs
      fulfilled International Society of Quality of Life Research's minimum standards,
      hindering specific recommendations. CONCLUSIONS: There is very limited evidence
      supporting the measurement properties of existing PROMs used in the context of
      recovery after abdominal surgery. This precludes the use of these PROMs to
      support value-based surgical care. Further research is required to bridge this
      major knowledge gap. REVIEW REGISTRATION: International Prospective Register of
      Systematic Reviews (PROSPERO): CRD42014014349.

PMID- 28767560
TI  - Variation in Bariatric Surgery Episode Costs in the Commercially Insured:
      Implications for Bundled Payments in the Private Sector.
AB  - OBJECTIVE: To describe hospital-level variation in roux-en-Y gastric bypass
      (RYGB) and sleeve gastrectomy (SG) in Michigan. BACKGROUND: Bariatric surgery is
      an increasingly prevalent elective surgical procedure that will likely be
      considered for future bundled payment programs, both public and private. Past
      research in the Medicare population found that the index hospitalization is
      responsible for the majority of payment variation among hospitals. However, this
      research largely excluded SG, now the most commonly performed bariatric surgery
      procedure nationally. METHODS: We used data from a state-wide quality
      collaborative to calculate the average risk and price-adjusted 30-day episode
      payment for patients undergoing RYGB and SG procedures at Michigan hospitals
      between January 2009 and October 2014. We organized hospitals into quintiles and
      compared the variation in payments between highest and lowest-cost quintiles, and
      also the payment categories that drove this variation. RESULTS: We identified
      9035 patients undergoing RYGB (n = 4194) or SG (n = 4841) procedures at 31
      hospitals. The average price and risk-adjusted episode payment ranged from
      $11,874 in the lowest hospital quintile to $13,394 in the highest quintile,
      representing a difference of $1519 (12.8%). Payments for the index
      hospitalization accounted for the largest share of total episode costs for both
      procedure types. Despite representing 2.7% to 6.0% of payments across quintiles,
      postdischarge payments explained 22.6% of hospital variation in SG. Similarly,
      readmissions explained 24.5% of payment variation for SG episodes, despite
      representing between 1.2% and 4.4% of payments. CONCLUSIONS: Collectively, our
      findings suggest that there are previously underappreciated differences in
      episode payment variation between bariatric surgery procedures. SG may be more
      amenable to cost containment under bundled payment initiatives by virtue of the
      greater share of variation explained by readmission and postdischarge payments,
      components of episode payment more likely to be influenced by provider
      discretion.

PMID- 28767561
TI  - Mixed Reality in Visceral Surgery: Development of a Suitable Workflow and
      Evaluation of Intraoperative Use-cases.
AB  - OBJECTIVE: The paper evaluates the application of a mixed reality (MR)
      headmounted display (HMD) for the visualization of anatomical structures in
      complex visceral-surgical interventions. A workflow was developed and technical
      feasibility was evaluated. SUMMARY OF BACKGROUND DATA: Medical images are still
      not seamlessly integrated into surgical interventions and, thus, remain separated
      from the surgical procedure.Surgeons need to cognitively relate 2-dimensional
      sectional images to the 3-dimensional (3D) during the actual intervention. MR
      applications simulate 3D images and reduce the offset between working space and
      visualization allowing for improved spatial-visual approximation of patient and
      image. METHODS: The surgeon's field of vision was superimposed with a 3D-model of
      the patient's relevant liver structures displayed on a MR-HMD. This set-up was
      evaluated during open hepatic surgery. RESULTS: A suitable workflow for
      segmenting image masks and texture mapping of tumors, hepatic artery, portal
      vein, and the hepatic veins was developed. The 3D model was positioned above the
      surgical site. Anatomical reassurance was possible simply by looking up.
      Positioning in the room was stable without drift and minimal jittering. Users
      reported satisfactory comfort wearing the device without significant impairment
      of movement. CONCLUSION: MR technology has a high potential to improve the
      surgeon's action and perception in open visceral surgery by displaying 3D
      anatomical models close to the surgical site. Superimposing anatomical structures
      directly onto the organs within the surgical site remains challenging, as the
      abdominal organs undergo major deformations due to manipulation, respiratory
      motion, and the interaction with the surgical instruments during the
      intervention. A further application scenario would be intraoperative ultrasound
      examination displaying the image directly next to the transducer. Displays and
      sensor-technologies as well as biomechanical modeling and object-recognition
      algorithms will facilitate the application of MR-HMD in surgery in the near
      future.

PMID- 28767562
TI  - Deleterious Effect of RAS and Evolutionary High-risk TP53 Double Mutation in
      Colorectal Liver Metastases.
AB  - OBJECTIVE: To assess the impact of somatic gene mutations on survival among
      patients undergoing resection of colorectal liver metastases (CLM). BACKGROUND:
      Patients undergoing CLM resection have heterogeneous outcomes, and accurate risk
      stratification is necessary to optimize patient selection for surgery. METHODS:
      Next-generation sequencing of 50 cancer-related genes was performed from primary
      tumors and/or liver metastases in 401 patients undergoing CLM resection. Missense
      TP53 mutations were classified by the evolutionary action score (EAp53)-a novel
      approach that dichotomizes mutations as low or high risk. RESULTS: The most
      frequent somatic gene mutations were TP53 (65.6%), followed by KRAS (48.1%) and
      APC (47.4%). Double mutation in RAS/TP53, identified in 31.4% of patients, was
      correlated with primary tumor location in the right colon (P = 0.006). On
      multivariable analysis, RAS/TP53 double mutation was an independent predictor of
      shorter overall survival (hazard ratio 2.62, 95% confidence interval 1.41-4.87, P
      = 0.002). In patients with co-mutated RAS, EAp53 high-risk mutations were
      associated with shorter 5-year overall survival of 12.2%, compared with 55.7% for
      TP53 wild type (P < 0.001). The negative prognostic effects of RAS and TP53
      mutations were limited to tumors harboring mutations in both genes. CONCLUSIONS:
      Concomitant RAS and TP53 mutations are associated with decreased survival after
      CLM resection. A high EAp53 predicts a subset of patients with worse prognosis.
      These preliminary analyses suggest that surgical resection of liver metastases
      should be carefully considered in this subset of patients.

PMID- 28767563
TI  - Incidence and Risk Factors of Long-term Opioid Use in Elderly Trauma Patients.
AB  - OBJECTIVE: Evaluate the incidence and risk factors of opioid use 1 year after
      injury in elderly trauma patients. BACKGROUND: The current epidemic of
      prescription opioid misuse and overdose observed in North America generally
      concerns young patients. Little is known on long-term opioid use among the
      elderly trauma population. METHODS: In a retrospective observational multicenter
      cohort study conducted on registry data, all patients 65 years and older admitted
      (hospital stay >2 days) for injury in 57 adult trauma centers in the province of
      Quebec (Canada) between 2004 and 2014 were included. We searched for filled
      opioid prescriptions in the year preceding the injury, up to 3 months and 1 year
      after the injury. RESULTS: In all, 39,833 patients were selected for analysis.
      Mean age was 79.3 years (+/-7.7), 69% were women, and 87% of the sample was
      opioid-naive. After the injury, 38% of the patients filled an opioid prescription
      within 3 months and 10.9% [95% confidence interval (CI) 10.6%-11.2%] filled an
      opioid prescription 1 year after trauma: 6.8% (95% CI 6.5%-7.1%) were opioid
      naive and 37.6% (95% CI 36.3%-38.9%) were opioid non-naive patients. Controlling
      for confounders, patients who filled 2 or more opioid prescriptions before the
      injury and those who filled an opioid prescription within 3 months after the
      injury were, respectively, 11.4 and 3 times more likely to use opioids 1 year
      after the injury compared with those who did not fill opioid prescriptions.
      CONCLUSIONS: These results highlight that elderly trauma patients are at risk of
      long-term opioid use, especially if they had preinjury or early postinjury opioid
      consumption.

PMID- 28767564
TI  - Post-Treatment/Pre-operative PET Response Is Not an Independent Predictor of
      Outcomes for Patients With Gastric and GEJ Adenocarcinoma.
AB  - OBJECTIVE: To determine whether changes in positron emission tomography (PET)
      avidity correlated with histologic response and were independently associated
      with outcome. BACKGROUND: The implications of metabolic response to neoadjuvant
      therapy as measured by repeat PET imaging remain ill-defined for patients with
      gastric and gastroesophageal junction (GEJ) cancers. METHODS: We identified
      patients with gastric and GEJ adenocarcinoma who were evaluated with PET imaging
      before and following neoadjuvant treatment, and subsequently underwent curative
      resections. Spearman rank correlation and Cox proportional hazards regression
      were used to evaluate standardized uptake value (SUV) and histologic response,
      pathologic parameters, and disease-specific survival (DSS). RESULTS: From 2002 to
      2013, 192 patients met our inclusion criteria. The median SUVmax response was
      57.3% (range: -110% to 100%) for patients with GEJ cancers, with a corresponding
      median pathologic treatment response of 80% (range: 0% to 100%). The median
      SUVmax response was 32.5% (-230% to 100%) for patients with gastric cancers, with
      a corresponding median pathologic treatment response of 35% (range: 0% to 100%).
      The Spearman correlation between SUVmax response and histologic response was
      significant for patients with GEJ (rho = 0.19, P = 0.04) and gastric (rho = 0.44,
      P < 0.0001) cancers. For patients with GEJ (P <0.0001 to 0.046) and gastric
      cancers (P = 0.0003 to 0.016), histopathologic response and tumor staging
      predicted DSS. SUVmax response failed to demonstrate a relationship with DSS when
      entered into multivariable models containing conventional pathologic variables.
      CONCLUSION: Following completion of neoadjuvant therapy for gastric and GEJ
      adenocarcinoma, histopathologic staging remains the best predictor of outcome.
      Repeat post-treatment/preoperative PET imaging for the purpose of prognostication
      is of limited value.

PMID- 28767565
TI  - Small intestine follicular dendritic cell sarcoma with liver metastasis: A case
      report.
AB  - RATIONALE: Follicular dendritic cell sarcoma (FDCS) is a rare neoplasia composed
      of spindle or oval cells with follicular dendritic cell differentiation, usually
      occurring in lymphoid tissue. In this report, we present a case of FDCS of the
      small intestine with liver metastasis. PATIENT CONCERNS: A 19-year-old female
      presented with recent onset of left upper abdominal pain. Abdominal computed
      tomography scan showed a large tumor mass in the liver lateral segment with
      compression to the pancreas upper part, and a smaller mass in the terminal ileum,
      respectively. High serum levels of amylase and lipase were noted. Resection of
      the tumors was performed. Microscopically, both tumors consisted of ovoid to
      spindle-shaped nuclei cells admixed with some lymphocytes arranged in fascicles,
      whorls, storiform arrays. Immunohistochemistry demonstrated that the tumor cells
      were positive for follicular dendritic cell markers, including CD21, CD23, and
      CD35. Epstein-Barr virus encoding small RNA (EBER; Inform EBER probe; Ventana
      Medical Systems, Tucson, AZ) in situ hybridization was negative. DIAGNOSES:
      According to the clinicopathological features, diagnosis of FDCS of intestinal
      origin was made. INTERVENTIONS: Resection of tumors located in the liver and at
      the small intestine was performed. After the operation, patient received adjuvant
      vinblastin chemotherapy. OUTCOMES: There was no evidence of recurrence at 8-month
      follow-up. LESSONS: It was unusual for FDCS of intestinal origin with liver
      metastasis and expressing with high serum levels of pancreatic enzymes.

PMID- 28767566
TI  - Shi-style cervical manipulations for cervical radiculopathy: A multicenter
      randomized-controlled clinical trial.
AB  - BACKGROUND: There is a lack of high-quality evidence supporting the use of
      manipulation therapy for patients with cervical radiculopathy (CR). This study
      aimed to evaluate the effectiveness of Shi-style cervical manipulations (SCMs)
      versus mechanical cervical traction (MCT) for CR. METHODS: This was a randomized,
      open-label, controlled trial carried out at 5 hospitals in patients with CR for
      at least 2 weeks and neck pain. The patients received 6 treatments of SCM (n =
      179) or MCT (n = 180) over 2 weeks. The primary outcome was participant-rated
      disability (neck disability index), measured 2 weeks after randomization. The
      secondary outcomes were participant-rated pain (visual analog scale) and health
      related quality of life (36-Item Short Form Health Survey [SF-36]). Assessments
      were performed before, during, and after (2, 4, 12, and 24 weeks) intervention.
      RESULTS: After 2 weeks of treatment, the SCM group showed a greater improvement
      in participant-rated disability compared with the control group (P = .018). The
      SCM group reported less disability compared with the control group (P < .001)
      during the 26-week follow-up. The difference was particularly important at 6
      months (mean -28.91 +/- 16.43, P < .001). Significant improvements in SF-36 were
      noted in both groups after 2 weeks of treatment, but there were no differences
      between the 2 groups. CONCLUSION: SCM could be a better option than MCT for the
      treatment of CR-related pain and disability.

PMID- 28767567
TI  - A 4 and a half years old boy with mesenchymal hamartomas in the left lateral lobe
      of the liver: A case report and literature review.
AB  - RATIONALE: Mesenchymal hamartomas of the liver is one type of rare liver tumor.
      PATIENT CONCERNS: Mesenchymal hamartomas of the liver (MHL) is rarely reported in
      the left lobe of the liver in children who are more than 2 years old. It is
      difficult to distinguish it from liver lesions such as hepatoblastoma in
      children, and hepatocellular carcinoma and focal nodular hyperplasia in adults.
      In addition, it is hard to correctly diagnose it without pathological
      examination. DIAGNOSES: Mesenchymal hamartomas of the liver. INTERVENTIONS: This
      patient underwent an operation assisted by the Da Vinci surgical system and the
      tumor was completely resected. OUTCOMES: No tumor recurrence or metastasis was
      observed 14 months after operation. LESSONS: MHL is a benign tumor that is
      difficult to diagnose due to the lack of specific clinical symptoms and signs.
      The management of MHL remains controversial. To achieve a good long-term outcome,
      complete resection of MHL is recommended.

PMID- 28767568
TI  - Three-dimensional virtual planning in precise chimeric fibula free flap for
      metacarpal defects: A case report.
AB  - RATIONALE: Metacarpal and phalanx defects with soft tissue loss were suggested to
      be reconstructed by vascularized bone flap. The fibular osteocutaneous flap is a
      preferred method. Three-dimensional virtual planning has successfully applied in
      mandibular reconstruction with fibular free flap. We applied three-dimensional
      virtual planning in precise fibula flap harvest to maintain the continuity of the
      fibula and to achieve accurate metacarpal and phalanx reconstruction. PATIENT
      CONCERNS: A 35-year-old male presented with extensive soft tissue defects and
      first metacarpal defect involving the first metacarpophalangeal joint. DIAGNOSES:
      There were 4 cm of first metacarpal defect involving the first
      metacarpophalangeal joint and soft tissue defects of 5cm * 3cm + 3cm * 2cm.
      INTERVENTIONS: By combining three-dimensional virtual planning, we harvested a
      chimeric fibular flap. The precise fibula partial osteotomies were performed with
      cutting guides designed in virtual planning. OUTCOMES: All the chimeric flaps
      survived and no significant donor-site morbidity was noted. Michigan Hand Outcome
      Questionnaire scores indicated acceptable functional results. LESSONS: Our
      preliminary experience with the approach of three-dimensional virtual planning in
      precise chimeric fibula free flap is practical and efficient. Although more cases
      and follow-up are needed to evaluate it, this approach is expected to benefit
      patients.

PMID- 28767569
TI  - Visual loss due to optic nerve infarction and central retinal artery occlusion
      after spine surgery in the prone position: A case report.
AB  - RATIONALE: Visual loss after spine surgery in the prone position is a serious
      complication. Several cases of central retinal artery occlusion with
      ophthalmoplegia after spine surgery have been reported in patients with
      ophthalmic arteries fed by the internal carotid artery (ICA) in a normal manner.
      PATIENT CONCERNS: A 74-year-old man developed visual loss after undergoing a
      spinal decompression and fusion operation in the prone position that lasted
      approximately 5 hours. DIAGNOSES: We detected an extremely rare case of visual
      loss due to optic nerve infarction and central retinal artery occlusion through
      fundoscopic examination, fluorescein angiogram, brain magnetic resonance imaging,
      and magnetic resonance angiography. The patient's visual loss may have been
      caused by compromised retrograde collateral circulation of the ophthalmic artery
      from branches of the external carotid artery in the presence of proximal ICA
      occlusion after a spinal operation in the prone position. INTERVENTIONS: To
      recover movement of the left extraocular muscles, the patient received
      intravenous injections of methylprednisolone for 3 days and then oral
      prednisolone for 6 days. OUTCOMES: Twenty days after the treatment, the motion of
      the left extraocular muscles was significantly improved. However, recovery from
      the left visual loss did not occur until 4 months after the operation. LESSONS:
      In high-risk patients with retrograde collateral circulation of the ophthalmic
      artery from the external carotid artery due to proximal ICA occlusion, various
      measures, including the use of a head fixator to provide a position completely
      free of direct compression of the head and face, should be considered to decrease
      the risk of postoperative visual loss.

PMID- 28767570
TI  - Effects of oxycodone on immune function in patients undergoing radical resection
      of rectal cancer under general anesthesia.
AB  - This study aims to explore the effect of oxycodone hydrochloride injection on the
      immune function of patients who underwent radical resection of rectal cancer
      under general anesthesia.Eighty patients were enrolled and randomly divided into
      group A and B (n = 40, each). All patients underwent general intravenous
      anesthesia. At the end of surgery, each patient in group A was injected with 5 mg
      (5 mL) of oxycodone hydrochloride, while 5 mg (5 mL) of morphine hydrochloride in
      group B. Venous blood was withdrawn in both groups at different time points.
      Changes in the numbers of T lymphocyte subsets and natural killer (NK) cells were
      determined by flow cytometry.First the numbers of T lymphocyte subsets and NK
      cells at T1, T2, T3, and T4 decreased in both groups, compared with those at T0,
      and the differences were statistically significant. Furthermore, the numbers
      reduced to a minimum at T2 and began to recover at T3. Second the differences
      between group A and B at T1, T2, T3, and T4 were statistically significant; and
      the numbers of T lymphocytes and NK cells were higher in group A than in group B
      at corresponding time points.Oxycodone hydrochloride and morphine hydrochloride
      both have inhibitory effects on immune function in patients undergoing radical
      resection of rectal cancer after surgery. However, oxycodone hydrochloride has a
      smaller effect compared to morphine hydrochloride.

PMID- 28767571
TI  - Candida vertebral osteomyelitis (CVO) 28 cases from a 10-year retrospective study
      in France.
AB  - Although increasingly frequent, little is known about the clinical presentation,
      radiological signs, and outcome of Candida vertebral osteomyelitis (CVO).We
      performed a nationwide retrospective study of laboratory-confirmed cases of CVO
      over a 10 year-period in France with a prolonged follow-up. We describe
      demographic, clinical, biological, and radiological characteristics of patients
      with CVO, patients' management, and long-term outcome and determine factors
      associated with a poor outcome.In total, 28 patients with laboratory-confirmed
      CVO were included. A prior systemic Candida infection was evidenced in 13/28
      (46%), occurring a median of 6 weeks before CVO was diagnosed. Twenty-six of 28
      (93%) had at least 1 underlying condition at risk of invasive fungal disease, and
      in 19/28 (68%) CVO was health-care related. C albicans was most frequently
      identified (21/28; 75%) Lumbo-sacral involvement was the most prevalent (20/28
      71%). Nearly half patients had no fever at presentation, but all had pain.
      Initial antifungal therapy consisted in fluconazole in 15/28 (53%); surgery was
      needed in 5 (18%) cases.One-year mortality was 21% (6/28), directly related to
      fungal infection in 2 patients. Risk-factors associated with 1-year mortality
      were age (P=.02), a high Charlson comorbidity index (P = .001), and a shorter
      treatment duration (median, 3 months vs 6 months; P = .02). Among 22 patients who
      survived, the median follow up duration was 15.5 months (8-93.5); 10 had
      sequelae, consisting in pain in all and neurological deficit in one. A longer
      treatment duration was significantly associated with healing without sequelae (P
      = .04).CVO concerns patients with serious underlying conditions and risk-factors
      for invasive candidiasis. Prolonged antifungal treatment appears to improve
      survival without sequelae.

PMID- 28767572
TI  - Relationship between the small cervical vertebral body and the morbidity of
      cervical spondylosis.
AB  - This study aimed to determine the relationship between the size of the cervical
      vertebral body and the morbidity of cervical spondylosis, and to examine the
      characteristics of spondylosis patients with small cervical vertebral bodies.The
      clinical data and the sagittal reconstructions of computed tomography images of
      182 patients with cervical spondylosis were collected retrospectively. Patients
      included 74 males and 108 females, with a mean age of 31.8 years (range 20-40
      years). The Torg-Pavlov ratio and the sagittal diameter of the vertebral body
      were measured. A Torg-Pavlov ratio above 1.2 was regarded as a small cervical
      vertebral body (SCVB), and below 1.2 as a nonsmall vertebral body (NSCVB).The
      NSCVB group was more prone to neurological symptoms than was the SCVB group (P <
      .05). There was no significant difference in neck pain between the 2 groups (P >
      .05). Conservative treatment achieved similar recovery rates in the SCVB group
      and the NSCVB group (81.8% vs 93.6%; P > .05). The rate of symptom (eg, axial
      neck pain) recurrence and persistence in the SCVB group was significantly higher
      than in the NSCVB group (P < .05).Our study found that smaller size of the
      cervical vertebral body is an attributing factor for cervical spondylosis.
      Patients with smaller cervical vertebral bodies are prone to persistent axial
      neck pain, but not neurological symptoms.

PMID- 28767573
TI  - Endoscopic resection for small esophageal submucosa tumor: Band ligation versus
      conventional endoscopic mucosal resection.
AB  - Because an esophageal submucosa tumor (SMT) may be malignant despite its small
      size, a safe endoscopic resection method is needed in some small SMTs.
      Conventional endoscopic mucosal resection (EMR) may be simple, but incomplete
      pathologic resection margin status is common. We aimed to investigate the
      clinical outcomes of 2 kinds of EMR techniques (conventional EMR and EMR with
      band ligation device) and to evaluate the factors associated with incomplete
      pathologic resection.We evaluated the medical records of 36 patients. All lesions
      were esophageal SMTs located in the submucosa or muscularis mucosa less than 10
      mm in size by endoscopic ultrasound (EUS). The clinical outcomes based on the
      endoscopic procedures and factors associated with incomplete pathologic resection
      were evaluated.The mean tumor size was 6.6 +/- 4.1 mm. The overall en bloc and
      complete resection rates were 100% and 80.6%, respectively. No procedure-related
      complications, such as perforation and bleeding, were found. Univariate analysis
      showed that complete resection rates were higher in granular cell tumors than in
      leiomyomas (82.8% vs 17.2%, P = .029), tumors located in the submucosa layer than
      in the muscularis mucosa (96.6% vs 3.4%, P = .003), and in EMR with band ligation
      device than in conventional EMR (82.8% vs 17.2%, P < .001). Multivariate analysis
      showed that conventional EMR was the only significant factor associated with
      incomplete resection (OR, 35.594; 95% CI, 2.042-520.329; P = .014)EMR with a band
      ligation device is an effective and safe treatment method for small esophageal
      SMT.

PMID- 28767574
TI  - Increased risk of Eustachian tube disorders in patients with sleep-disordered
      breathing.
AB  - Sleep-disordered breathing (SDB) and Eustachian tube disorders (ETDs) share the
      same risk factors. The specific aim of this study was to determine the
      correlation between these 2 conditions and to determine whether treatments for
      SDB reduce the risk of ETD.This is a retrospective and large population-based
      cohort study. According to Taiwan's National Health Insurance Research Database,
      out of 1,000,000 insured patients, 24,251 patients were newly diagnosed with SDB
      from year 2000 through 2009. The control group for this study comprised 96,827
      patients without SDB who were randomly selected from the same database at a ratio
      of 1:4, frequency matched for sex, age, and index year of SDB. The incidence of
      developing ETD was compared between these 2 groups; the main covariates were
      demographic data, interventions, and medical comorbidities.There was an increased
      risk of developing ETD among the SDB cohort compared with the control group
      (hazard ratio = 1.51, 95% confidence interval = 1.41-1.63). Compared with SDB
      patients who did not receive treatment, those who received the treatment, that
      is, pharyngeal or nasal surgery, CPAP, or multiple modalities (both surgery and
      CPAP), had a significantly reduced risk of developing ETD.This study showed that
      patients with SDB are at an increased risk of developing ETD and other
      comorbidities. The risk of developing ETD can be reduced by implementing prompt
      treatment for SDB. Multidisciplinary evaluation including ETD should be conducted
      in the management of patients presenting with SDB.

PMID- 28767575
TI  - DNMT3A mutations in Chinese childhood acute myeloid leukemia.
AB  - BACKGROUND: DNA methyltransferase 3A (DNMT3A) mutations have been found in
      approximately 20% of adult acute myeloid leukemia (AML) patients and in 0% to
      1.4% of children with AML, and the hotspots of mutations are mainly located in
      the catalytic methyltransferase domain, hereinto, mutation R882 accounts for 60%.
      Although the negative effect of DNMT3A on treatment outcome is well known, the
      prognostic significance of other DNMT3A mutations in AML is still unclear. Here,
      we tried to determine the incidence and prognostic significance of DNMT3A
      mutations in a large cohort in Chinese childhood AML. METHODS: We detected the
      mutations in DNMT3A exon 23 by polymerase chain reaction and direct sequencing in
      342 children with AML (0-16 years old) from January 2005 to June 2013, treated on
      BCH-2003 AML protocol. The correlation of DNMT3A mutations with clinical
      characteristics, fusion genes, other molecular anomalies (FLT3 internal tandem
      duplication [FLT3-ITD], Nucleophosmin 1, C-KIT (KIT proto-oncogene receptor
      tyrosine kinase), and Wilms tumor 1 mutations), and treatment outcome were
      analyzed. RESULTS: DNMT3A mutations were detected in 4 out of 342 (1.2%)
      patients. Two patients were PML-RARA positive and 1 patient was FLT3-ITD
      positive. The mutations in coding sequences included S892S, V912A, R885G, and
      Q886R. Furthermore, there was 1 intronic mutation (c.2739+55A>C) found in 1
      patient. No association of DNMT3A mutations with common clinical features was
      found. Two patients with DNMT3A mutations died of relapse or complications during
      treatment. One patient gave up treatment due to remission induction failure in
      day 33. Only 1 patient achieved continuous complete remission. CONCLUSIONS:
      DNMT3A mutations were rare in Chinese children with AML including PML-RARA
      positive APL. The mutation positions were different from the hotspots reported in
      adult AML. DNMT3A mutations may have adverse impact on prognosis of children with
      AML.

PMID- 28767576
TI  - Association between costs and quality of acute myocardial infarction care
      hospitals under the Korea National Health Insurance program.
AB  - If cost reductions produce a cost-quality trade-off, healthcare policy makers
      need to be more circumspect about the use of cost-effective initiatives.
      Additional empirical evidence about the relationship between cost and quality is
      needed to design a value-based payment system. We examined the association
      between cost and quality performances for acute myocardial infarction (AMI) care
      at the hospital level.In 2008, this cross-sectional study examined 69 hospitals
      with 6599 patients hospitalized under the Korea National Health Insurance (KNHI)
      program. We separately estimated hospital-specific effects on cost and quality
      using the fixed effect models adjusting for average patient risk. The analysis
      examined the association between the estimated hospital effects against the
      treatment cost and quality. All hospitals were distributed over the 4 cost *
      quality quadrants rather than concentrated in only the trade-off quadrants (i.e.,
      above-average cost and above-average quality, below-average cost and below
      average quality). We found no significant trade-off between cost and quality
      among hospitals providing AMI care in Korea.Our results further contribute to
      formulating a rationale for value-based hospital-level incentive programs by
      supporting the necessity of different approaches depending on the quality
      location of a hospital in these 4 quadrants.

PMID- 28767577
TI  - Influence of oxygen content immediately after graft reperfusion on occurrence of
      postoperative acute kidney injury in living donor liver transplantation.
AB  - Acute kidney injury (AKI) is a common complication after living donor liver
      transplantation (LDLT). In this study, we investigated perioperative factors,
      including oxygen content, related to the postoperative development of AKI after
      LDLT. The perioperative data of 334 patients were reviewed retrospectively. We
      identified the postoperative development of AKI based on the Acute Kidney Injury
      Network criteria. Perioperative variables, including oxygen content, were
      compared between patients with and without AKI. Potentially significant variables
      in a univariate analysis were evaluated by multivariate analysis. Postoperative
      AKI developed in 76 patients (22.7%). Univariate analysis revealed that
      preoperative factors (body mass index [BMI], diabetes mellitus, C-reactive
      protein) and intraoperative factors (severe postreperfusion syndrome, packed red
      blood cell transfusion, furosemide, and oxygen content at the anhepatic phase, 5
      minutes and 1 hour after graft reperfusion, and at peritoneal closure) of
      recipients were significant. The multivariate analysis showed that oxygen content
      5 minutes after graft reperfusion, BMI, and furosemide administration were
      independently associated with postoperative AKI. In conclusion, postoperative AKI
      was independently associated with oxygen content 5 minutes after graft
      reperfusion, BMI, and furosemide administration. Meticulous ventilator care and
      transfusion should be required to maintain sufficient oxygen content immediately
      after graft reperfusion in patients who undergo LDLT.

PMID- 28767578
TI  - Enhanced recovery after surgery program reduces length of hospital stay and
      complications in liver resection: A PRISMA-compliant systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Many enhanced recovery after surgery (ERAS) guidelines have already
      been established in several kinds of surgeries. But due to concerns of the
      specific complications, it has not yet been considered the standard of care in
      liver surgery. OBJECTIVE: The aim of this review is to assess the effect of ERAS
      in patients undergoing liver surgery. METHODS: EMBASE, CNKI, PubMed, and the
      Cochrane Database were searched for randomized controlled trials (RCTs) comparing
      ERAS with conventional care in patients undergoing liver surgery. Subgroup meta
      analysis between laparoscopic and open surgical approaches to liver resection was
      also conducted. RESULTS: Seven RCTs were included, representing 996 patients.
      Length of stay (LOS) (MD -3.17, 95% CI: -3.99 to -2.35, P < .00001, I = 89%) and
      time to first flatus (MD -0.9, 95% CI: -1.36 to -0.45, P = .0001, I = 98%) were
      both reduced in the ERAS group. There were also fewer complications in the ERAS
      group (OR 0.52, 95% CI: 0.37-0.72, P < .0001, I = 0%). CONCLUSION: The ERAS
      program can obviously enhance short-term recovery after liver resection. It is
      safe and worthwhile. A specific ERAS guideline for liver resection is
      recommended.

PMID- 28767579
TI  - The identification of the TRPM8 channel on primary culture of human nasal
      epithelial cells and its response to cooling.
AB  - BACKGROUND: It has been proposed that the transient receptor potential (TRP)
      channel Melastatin 8 (TRPM8) is a cold-sensing TRP channel. However, its presence
      and its role in the nasal cavity have not yet been fully studied. METHODS:
      Immunohistology was used to study TRPM8 receptors in both the nasal mucosa tissue
      and the primary cultures of human nasal cells. Cells from primary cultures were
      immunostained with antibodies to TRPM8, mucin, cytokeratin (CK)-14, CK-18, and
      vimentin. Western blotting and real-time polymerase chain reaction (PCR) were
      used to determine the physiological role of TRPM8 in mucus production in the
      nasal cavity, with and without its agonist and antagonist. RESULTS: The TRPM8 is
      clearly present in the epithelium, mucous glands, and vessels. No obvious TRPM8
      immunoreactive cells were detected in the connective tissue. Immunostaining of
      cytospin preparations showed that epithelial cells test positive for CK-14, CK
      18, TRPM8, and mucin 5AC (MUC5AC). Fibroblastic cells are stained negative for
      TRPM8. Secreted mucins in the cultured supernatant are detected after exposure to
      menthol and moderate cooling to 24 degrees C. Both induce a statistically
      significant increase in the level of MUC5AC mRNA and mucin production. BCTC, a
      TRPM8 antagonist, has a statistically significant inhibitory effect on MUC5AC
      mRNA expression and MUC5AC protein production that is induced by menthol and
      moderate cooling to 24 degrees C. CONCLUSIONS: The study demonstrates that TRPM8
      is present in the nasal epithelium. When it is activated by moderate cooling to
      24 degrees C or menthol, TRPM8 induces the secretion of mucin. This study shows
      that TRPM8 channels are important regulators of mucin production. Therefore,
      TRPM8 antagonists could be used to treat refractory rhinitis.

PMID- 28767580
TI  - Metastatic cardiac tumor presenting as atrial fibrillation in a previously
      healthy woman: A case report.
AB  - RATIONALE: Metastatic cardiac tumor (MCT) is rare in clinical practice. MCT
      presenting initially as atrial fibrillation (AF) is even rarer. PATIENT CONCERNS:
      We report a 47-year-old woman with no previous medical history presented with
      intermittent palpitation for 3 days. DIAGNOSES: The electrocardiography showed AF
      with rapid ventricular rate. The transthoracic echocardiography showed a 4 * 4 cm
      mass occupying the left atrium (LA). The contrast enhanced computed tomography
      (CT) showed a left lower lung mass with invasion to the LA and left upper
      pulmonary vein (PV). The chest CT guided biopsy revealed poorly differentiated
      squamous cell carcinoma. Further workup including bone scan showed no significant
      findings. The diagnosis of lung squamous cell carcinoma with cardiac invasion was
      made. INTERVENTIONS: She went on to received palliative chemotherapy. OUTCOMES:
      She is being followed up regularly at the outpatient department. LESSONS: Tumor
      invasion of the LA and PV was thought to be the cause of the AF. This condition
      is rare, but clinically important. Physicians should be alert that MCT could be
      an important differential diagnosis in patients presenting with unexplained AF.

PMID- 28767582
TI  - Gallstone prevalence and risk factors in patients with ulcerative colitis in
      Korean population.
AB  - This study aims to evaluate the prevalence, risk factors, and relative risk of
      gallstones and associated disease in patients with ulcerative colitis (UC).
      Medical records of 311 patients diagnosed with UC between January 2004 and
      February 2015 were reviewed retrospectively. To assess relative risk, 622
      patients matched by age, sex, and body mass index were included as a control
      group. Gallstones were detected in 8% (25/311) of UC patients and in 3.9%
      (24/622) of the control group. Prevalence was significantly higher in the UC
      group (odds ratio [OR], 2.178; P = .007). Mean age of gallstone patients was 57.1
      +/- 17.8 years in the UC group, and mean disease duration of UC was 67.2 +/- 38.8
      months. The male-to-female ratio of gallstone patients in the UC group was
      2.13:1. Mean interval from diagnosis of UC to detection of gallstones was 17.8 +/
      30 months. Six UC patients with gallstones underwent cholecystectomy or
      endoscopic retrograde cholangiography for symptomatic disease and complications.
      In univariate analysis, diabetes, hypertension, age >=65 years, and history of
      more than 3 admissions were significantly associated with gallstone in UC
      patients. In multivariate analysis, age >=65 years (OR, 2.655; P = .033) and
      hospitalization >=3 times (OR, 4.1; P = .001) were statistically significant risk
      factors for gallstones in UC patients. This study shows that UC patients have a
      significantly higher risk of gallstones compared to the general population (OR,
      2.178; P = .007), especially those who are older, with a history of multiple
      admissions.

PMID- 28767581
TI  - Diagnostic value of PET/CT for giant cell arteritis combined with pulmonary
      embolism presenting: Case report and literature review.
AB  - RATIONALE: Giant cell arteritis (GCA) combined with concomitant pulmonary
      embolism (PE) is extremely difficult to diagnose because of its low incidence and
      atypical clinical presentations. PATIENT CONCERNS: A 62-year-old male developed
      fever of unknown origin. DIAGNOSES: Positron emission tomography/computed
      tomography (PET/CT) revealed increased glucose metabolism in the vascular walls
      of the ascending and descending aorta and pulmonary artery, leading to a
      diagnosis of GCA combined with PE. INTERVENTIONS: The patient did not respond to
      regular antiviral and antibacterial treatment but was remised after steroid
      treatment. OUTCOMES: No specific autoantibodies were positive for this patient,
      and the patient did not respond to regular antiviral and antibacterial treatment.
      After diagnosed by PET/CT, the patient responded well to steroid treatment.
      Literature review found 16 cases of GCA diagnosed by PET/CT. Their median age was
      68.5 (range, 21-87) years and 13 cases were female. PET/CT showed significantly
      increased metabolism in the ascending and descending aorta, abdominal aorta, and
      carotid artery. In 4 cases (including our own case), the mean maximum
      standardized uptake value was 4.2 +/- 1.7 (range, 2.5-7.2). Six cases of GCA also
      had PE and 5 (6/7, 85.7%) cases were females, and the current case is the first
      male case of GCA combined with PE. Steroid therapy was initiated in all 5 cases.
      Complete remission was achieved in 4 cases and 2 patients died and the outcome of
      1 patient was unknown. LESSONS: Our case and the review highlight the value of
      PET/CT in diagnosing GCA combined with PE, suggesting that PET/CT is the
      preferred diagnostic tool for atypical patients presenting with fever or muscle
      pain.

PMID- 28767583
TI  - Percentage change of primary tumor on 18F-FDG PET/CT as a prognostic factor for
      invasive ductal breast cancer with axillary lymph node metastasis: Comparison
      with MRI.
AB  - We evaluated the prognostic value of quantitative parameters using dual time
      point (DTP) F-FDG PET/CT (PET/CT) in invasive ductal breast cancer (IDC) with
      metastatic axillary lymph nodes (ALN) as compared with dynamic contrast-enhanced
      (DCE) and diffusion-weighted (DW) MRI.Seventy patients with IDC and metastatic
      ALN were retrospectively registered. Static PET parameters including maximum
      standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion
      glycolysis (TLG) of primary tumor, SUVmax of ALN (SUVALN), and percentage changes
      (Delta%) in those parameters were measured with DTP PET/CT. From DCE MRI, peak
      enhancement value, total tumor angio volume, and proportions of kinetic curve
      types on delayed-phases were investigated. The average apparent diffusion
      coefficient (ADCavg) was estimated on DWI. To demonstrate the prognostic value of
      quantitative imaging parameters for recurrence-free survival (RFS), univariate
      and multivariate analyses were performed using those parameters and
      clinicohistologic variables.All static PET parameters, %DeltaSUVmax, %DeltaMTV,
      and %DeltaSUVALN on DTP PET/CT and ADCavg on DWI were significantly predictive
      for disease recurrence. Of clinicohistologic variables, pathologic tumor (pT)
      diameter, pathologic ALN stage, tumor grade, and hormonal status also were
      significantly prognostic. After multivariate analysis, %DeltaSUVmax > 25.05 (P =
      .043), ADCavg <= 1016.55 (P = .020), pT diameter > 3 cm (P = .001), and ER
      negative status (P = .002) were independent prognostic factors for poor
      outcome.Only %DeltaSUVmax of the primary tumor on PET/CT together with ADCavg, pT
      diameter, and ER status was an independent prognostic factor for predicting
      relapse in IDC with metastatic ALN. Percentage change of primary tumor on
      preoperative PET/CT may be a valuable imaging marker for selecting IDC patients
      that require adjunct treatment to prevent relapse.

PMID- 28767584
TI  - Effects of a rational-emotive health education intervention on stress management
      and irrational beliefs among technical college teachers in Southeast Nigeria.
AB  - BACKGROUND: Stress is the product of how an individual reacts and adapts to the
      specific demands and threats they encounter while carrying out given tasks. The
      main purpose of this study was to investigate the effects of a rational-emotive
      health education intervention (REHEI) on stress management, and irrational
      beliefs in a sample of technical college teachers in Southeast Nigeria. METHOD:
      The study design was a pretest-posttest control group. Repeated measures analysis
      of variance, paired t test and Mann-Whitney U tests were used to analyze the data
      collected. RESULTS: The REHEI significantly reduced teacher stress in those
      teaching staff exposed to the treatment intervention, relative to a waitlist
      control group. Furthermore, the REHEI program significantly decreased irrational
      beliefs about teaching in those teaching staff exposed to the treatment
      intervention compared to a waitlist control group. CONCLUSION: The REHEI program
      can be used to coach teachers on how to manage and cope with stress and overcome
      irrational beliefs in teaching.

PMID- 28767585
TI  - Pent-up demand for surgery in the Manaus metropolitan region: A population-based
      cross-sectional study.
AB  - Waiting lines in healthcare reflect an imbalance between the availability and the
      demand for medical services. This study aimed to analyze the prevalence and
      factors associated with the pent-up demand for surgical procedures in the Manaus
      metropolitan region.We performed a population-based cross-sectional study in
      2015. Pent-up demand was based on self-report by the participants; those who
      reported waiting were contacted by phone to clarify the nature and reasons for
      the experienced delay.We interviewed 4001 adults in their households. The pent-up
      demand for surgical procedures in the Manaus metropolitan region was 14% (95%
      confidence interval: 13-15%). The surgical specialties with the highest demand
      included orthopedics (18.1%), gynecology (17.0%), ophthalmology (12.4%),
      neurosurgery (10.8%), and general surgery (10.2%). The main reason for not
      accessing services was their lack of availability in the public health system,
      leading some patients to pay for procedures in private facilities. The
      populations most affected by pent-up demand included elderly individuals, women,
      and housewives.Pent-up demand for surgical procedures is a common problem in the
      Manaus metropolitan region and thus requires coordinated actions to optimize
      access to and capacity of the healthcare system.

PMID- 28767586
TI  - Association between hemorrhoid and risk of coronary heart disease: A nationwide
      population-based cohort study.
AB  - The purpose of the study was to address the association between hemorrhoid and
      the subsequent risk of coronary heart disease (CHD) development.This
      retrospective cohort study used reimbursement claims data from the Longitudinal
      Health Insurance Database 2000 in Taiwan. Thirty-three thousand thirty-four
      patients with hemorrhoids and 132,136 age-, gender-, and index year matched
      controls between 2000 and 2010 were identified. Cox model was performed to
      estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of CHD
      development for the hemorrhoid cohort compared with the nonhemorrhoid
      cohort.During a follow-up period of 12 years, the overall incidence rate of CHD
      was 9.91 per 1000 person-years in the hemorrhoid patients and was 1.36-fold
      higher than in the nonhemorrhoid cohort (7.28 per 1000 person-years) with an
      adjusted hazard ratio (aHR) of 1.27 (95% CI = 1.21-1.34). Moreover, compared with
      the nonhemorrhoid patients without these comorbidities, among patients with
      hemorrhoids, those with any 2 comorbidities were at a significantly increased
      risk of CHD (HR = 7.12, 95% CI = 6.61-7.67; P < .001), followed by those with any
      1 comorbidity (HR = 3.23, 95% CI = 2.94-3.54; P < .001).We found that hemorrhoid
      patients had a 1.27-fold higher risk of CHD compared with those without
      hemorrhoids after adjusting for the potential confounding factors.

PMID- 28767587
TI  - Histone deacetylase HDAC1 expression correlates with the progression and
      prognosis of lung cancer: A meta-analysis.
AB  - BACKGROUND: Histone deacetylase 1 (HDAC1) is an important epigenetic factor, and
      is thought to be associated with the progression and prognosis of some types of
      cancer. HDAC1 has been reported to be overexpressed in lung cancer, but the
      correlation between HDAC1 overexpression and the clinical features or prognosis
      of lung cancer is controversial. In this study, we investigated the potential
      association between HDAC1 and lung cancer. MATERIALS AND METHODS: Embase, Web of
      Science, PubMed, and other sources were searched for relevant studies. Pooled
      odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (CI) were
      calculated to evaluate the association of HDAC1 with lung cancer risk. RESULTS:
      Eight eligible studies were included in the final meta-analysis. We found that
      HDAC1 mRNA or protein expression was closely associated with the differentiation
      grade of lung cancer (OR = 2.36, 95% CI = 1.14-4.87, P = .02). In addition, the
      protein expression level of HDAC1 in squamous cell carcinoma was higher than that
      in adenocarcinoma (OR = 1.81, 95% CI = 1.13-2.90, P = .01). Finally, HDAC1 mRNA
      or protein expression was negatively correlated with the overall survival rate of
      patients with lung cancer (HR = 2.40, 95% CI = 1.48-3.88, P = .0004). CONCLUSION:
      In this meta-analysis, our results suggest that HDAC1 may serve as a good
      diagnostic and prognostic marker for lung cancer.

PMID- 28767589
TI  - Effects of fenofibrate on inflammatory cytokines in diabetic retinopathy
      patients.
AB  - The role of cytokines in diabetic retinopathy (DR) and effects of fenofibrate on
      cytokines were explored by observing changes in serum IL-1beta, TNF-alpha, VEGF,
      and Lp-PLA2 in different stages of DR and the intervention effect of oral
      fenofibrate on cytokines.In total, 190 patients with type 2 DR were enrolled and
      divided into 3 groups: diabetic without retinopathy (NDR) group (n = 30),
      nonproliferative diabetic retinopathy (NPDR) group (n = 80), and proliferative
      diabetic retinopathy (PDR) group (n = 80). According to whether or not to accept
      fenofibrate treatment, NPDR and PDR groups were further divided into the NPDR
      control (NPDR1) group (n = 40) and the NPDR treatment (NPDR2) group (n = 40), and
      the proliferative diabetic retinopathy control (PDR1, n = 40) group and the
      proliferative diabetic retinopathy treatment (PDR2) group (n = 40). At 12 weeks
      after fenofibrate treatment, serum IL-1beta, TNF-alpha, VEGF, and Lp-PLA2 levels
      were detected.In PDR and NPDR patients, levels of serum cytokines such as IL
      1beta (120.56 +/- 27.32 pg/mL vs 112.34 +/- 19.45 pg/mL vs 82.9 +/- 13.8 pg/mL),
      TNF-alpha (125.86 +/- 25.57 pg/mL vs 109.48 +/- 20.15 pg/mL vs 80.7 +/- 12.8
      pg/mL), VEGF (166.65 +/- 37.74 pg/mL vs 148.54 +/- 36.27 pg/mL vs 88.97 +/- 24.86
      pg/mL), and Lp-PLA2 (172.34 +/- 45.22 MUg/L vs 154.66 +/- 40.98 MUg/L vs 125.88
      +/- 38.87 MUg/L) were significantly higher than in diabetes patients without
      retinopathy. After fenofibrate treatment, serum IL-1beta, TNF-alpha, VEGF, and Lp
      PLA2 significantly decreased in NPDR and PDR patients.Serum IL-1beta, TNF-alpha,
      VEGF, and Lp-PLA2 play an important role in occurrence and development of
      diabetic retinopathy. Fenofibrate can reduce cytokine levels in DR patients and
      improve inflammatory response.

PMID- 28767588
TI  - Successful ceftazidime-avibactam treatment of MDR-KPC-positive Klebsiella
      pneumoniae infection in a patient with traumatic brain injury: A case report.
AB  - RATIONALE: Carbapenem-resistant Enterobacteriaceae infections are a serious
      health care problem, because of the high mortality. Carbapenem resistance is
      mainly caused by carbapenemases production, including Klebsiella pneumoniae
      carbapenemase (KPC). Ceftazidime-avibactam is a new cephalosporin/beta-lactamase
      inhibitor combination for the treatment of complicated urinary, intra-abdominal
      infections, and nosocomial pneumonia caused by gram negative, or other serious
      gram-negative infections. PATIENT CONCERNS: We showed the case of a 27-year-old
      patient, hospitalized for traumatic brain injury and chest trauma, with KPC
      producing Klebsiella pneumoniae infection. DIAGNOSES: Blood and bronchial
      aspirate culture analysis detected an infection caused by MDR Klebsiella
      pneumoniae, resistant to meropenem, ertapenem, piperacillin/tazobactam,
      amoxicillin/clavulanic acid, aztreonam, ceftazidime, cefotaxime, cefepime,
      amikacin, ciprofloxacin, trimethoprim/sulfamethoxazole, colistin while it showed
      an intermediate sensitivity to gentamicin and was sensitive to ceftazidime
      avibactam. Molecular analyses revealed that the isolate belonged to the epidemic
      clone sequence type 258 (ST258) carrying blaKPC-3, blaTEM-1, and blaSHV-11genes.
      INTERVENTIONS: After various combined antibiotic therapies without improvements,
      he was treated with ceftazidime-avibactam, on a compassionate-use basis.
      OUTCOMES: With ceftazidime-avibactam monotherapy clinical and microbiological
      clearance was obtained. A week after the end of the therapy microbiological
      analysis was repeated and a positive rectal swab for KPC-Klebsiella pneumoniae
      was found, becoming negative after 1 month. Moreover, the patient did not show
      any relapses for up to 18 weeks. LESSONS: This case indicates that ceftazidime
      avibactam monotherapy could be efficacious against KPC positive Klebsiella
      pneumoniae infections.

PMID- 28767590
TI  - Combining situ-morcellation with continuous-fill-mattress suture in laparoscopic
      myomectomy: A surgical approach of choice for patients with large uterine
      fibroids.
AB  - BACKGROUND: To investigate the efficacy and advantage of combining situ
      morcellation with continuous-fill-mattress suture compared with conventional
      morcellation and suture in laparoscopic myomectomy. METHODS: One hundred sixteen
      patients who underwent laparoscopic myomectomy from March 2014 to October 2016.
      INTERVENTIONS: Patients were divided into combining situ-morcellation with
      continuous-fill-mattress suture group (n = 62) and conventional group (n = 54),
      and subsequent statistical analysis the clinical data of the 2 groups. RESULTS:
      The combining situ-morcellation with continuous-fill-mattress suture group shows
      significantly decrease of surgery time, incision size, blood loss, postoperative
      drainage volume and time, postoperative vent time, hospital stay and the loss of
      hemoglobin value. Moreover, there is significant significance between the 2
      groups in the surgery time (P = .018), the postoperative drainage volume (P =
      .000), and the loss of hemoglobin value (P = .000). CONCLUSIONS: The combining
      situ-morcellation with continuous-fill-mattress suture shows significant
      advantages in shortening surgery time and reducing blood loss compared with
      conventional group in laparoscopic myomectomy.

PMID- 28767591
TI  - Identification of key genes associated with rheumatoid arthritis with
      bioinformatics approach.
AB  - We aimed to identify key genes associated with rheumatoid arthritis (RA).The
      microarray datasets of GSE1919, GSE12021, and GSE21959 (35 RA samples and 32
      normal controls) were downloaded from the Gene Expression Omnibus database.
      Differentially expressed genes (DEGs) in RA samples were identified using the t
      test in limma package. Functional enrichment analysis was performed using
      clusterProfiler package. A protein-protein interaction (PPI) network of selected
      DEGs was constructed based on the Human Protein Reference Database. Active
      modules were explored using the jActiveModules plug-in in the Cytoscape Network
      Modeling package.In total, 537 DEGs in RA samples were identified, including 241
      upregulated and 296 downregulated genes. A total of 24,451 PPI pairs were
      collected, and 5 active modules were screened. Furthermore, 19 submodules were
      acquired from the 5 active modules. Discs large homolog 1 (DLG1) and related DEGs
      such as guanylate cyclase 1, soluble, alpha 2 (GUCY1A2), N-methyl d-aspartate
      receptor 2A subunit (GRIN2A), and potassium voltage-gated channel member 1
      (KCNA1) were identified in 8 submodules. Plasminogen (PLG) and related DEGs such
      as chemokine (C-X-C motif) ligand 2 (CXCL2), laminin, alpha 3 (LAMA3), complement
      component 7 (C7), and coagulation factor X (F10) were identified in 4
      submodules.Our results indicate that DLG1, GUCY1A2, GRIN2A, KCNA1, PLG, CXCL2,
      LAMA3, C7, and F10 may play key roles in the progression of RA and may serve as
      putative therapeutic targets for treating RA.

PMID- 28767592
TI  - BMP4 rs17563 polymorphism and nonsyndromic cleft lip with or without cleft
      palate: A meta-analysis.
AB  - BACKGROUND: Previous studies have investigated the relationship between human
      bone morphogenetic protein 4 gene (BMP4) rs17563 polymorphism and nonsyndromic
      cleft lip with or without cleft palate (NSCL/P). However, the results remained
      inconsistent. Therefore, we conducted a meta-analysis to assess the effect of
      BMP4 rs17563 polymorphism on NSCL/P. METHODS: Electronic searches in 5 databases
      were conducted to select all eligible studies up to March 2017. Odds ratios (ORs)
      with the corresponding 95% confidence intervals (CIs) were calculated to estimate
      the association. Sensitivity analysis was performed to evaluate the results
      stability by excluding each study in turn. Publication bias was assessed by Begg
      funnel plots and Egger test. RESULTS: A total of 11 case-control studies were
      included in the meta-analysis. The pooled frequency of the minor allele C for
      BMP4 rs17563 was lower in Asians (pooled frequency = 0.33, 95% CI: 0.29-0.37)
      than in Brazilian population (pooled frequency = 0.47, 95% CI: 0.40-0.54). The
      overall results showed no significant association of BMP4 rs17563 polymorphism
      with NSCL/P risk. However, the results turned out to be different when stratified
      by ethnicity. BMP4 rs17563 polymorphism was associated with a higher risk of
      NSCL/P among Asian ethnicity (C vs T: OR = 1.33, 95% CI: 1.02-1.73; CC vs TT: OR
      = 2.10, 95% CI: 1.28-3.43; CC vs TT + TC: OR = 2.16, 95% CI: 1.34-3.47) and among
      Caucasian population (TC vs TT: OR = 3.36, 95% CI: 2.03-5.54; TC + CC vs TT: OR =
      3.71, 95% CI: 2.43-5.69). Among Brazilian population, BMP4 rs17563 polymorphism
      exerted a significantly protective effect on NSCL/P (C vs T: OR = 0.70, 95% CI:
      0.58-0.84; CC vs TT: OR = 0.54, 95% CI: 0.33-0.88; TC vs TT: OR = 0.55, 95% CI:
      0.44-0.69; TC + CC vs TT: OR = 0.56, 95% CI: 0.45-0.69). CONCLUSION: The results
      suggest that the C allele of BMP4 rs17563 may be a risk factor for NSCL/P among
      Asians and Caucasians, and may be a protective factor for NSCL/P in Brazilian
      population. Future large-sample studies with appropriate designs among specific
      populations are warranted to evaluate the association.

PMID- 28767593
TI  - The mini-incision technique for carpal tunnel release using nasal instruments in
      Chinese patients.
AB  - Treatment of carpal tunnel syndrome (CTS) remains a challenge for hand surgeons.
      Carpal tunnel release (CTR) using nasal instruments has the advantages of both
      endoscopy and open surgery. In this study we aimed to explore the effectiveness
      of CTR using nasal instruments in Chinese patients.We present a case series of 49
      cases of idiopathic CTS treated with the mini-incision technique using nasal
      instruments. The average recovery days before return to normal work and
      complications were recorded. The mean grip strength, pinch strength, and
      sensation were evaluated. Subjective results were evaluated using the visual
      analogue scale (VAS), Levine Carpal Tunnel Syndrome Questionnaire (LCTSQ),
      Disabilities of the Arm, Shoulder, and Hand (DASH), and Medical Outcomes Study
      (MOS) 36-item short-form health survey (SF-36).The mean follow-up was 13 months.
      No return of symptoms or blood vessel injury occurred. The incidence of scar
      tenderness was only 8.1%, later pillar pain (after 4 weeks) was 18.4%, and
      average recovery time to return to normal work was 23.7 days. The mean grip
      strength, pinch strength, and sensation were significantly improved (P < .001).
      The VAS, LCTSQ, and DASH survey postoperative mean scores were lower than the
      preoperative scores (P < .001). SF-36 scores were significantly increased
      following surgery (P < .001).We conclude that the mini-incision technique for CTR
      using nasal instruments in Chinese patients is safe, effective, and low cost. It
      is worthwhile for the technique to be promoted and used.

PMID- 28767594
TI  - Retroperitoneal bronchogenic cyst resembling an adrenal tumor with high levels of
      serum carbohydrate antigen 19-9: A case report.
AB  - RATIONALE: Retroperitoneal bronchogenic cysts without specific clinical
      manifestations are extremely rare and difficult to diagnose preoperatively and
      are easily misdiagnosed as left adrenal or pancreatic tumors. PATIENT CONCERNS: A
      48-year-old woman with the chief complaint of obscure epigastric pain for 1 month
      and with no other gastrointestinal symptoms and no significant medical history.
      The patient had signed informed consent for publication of this case report.
      DIAGNOSIS: The serum level of carbohydrate antigen 19-9 (CA 19-9) in the patient
      was >1200 U/mL, which far exceeded the normal level of <37 U/mL. Computed
      tomography (CT) initially suggested the presence of an adrenal tumor. However,
      endoscopic ultrasound (EUS) showed that the adrenal gland had an intact capsule
      and that the mass originated in the retroperitoneal space and did not involve the
      paranephros. INTERVENTIONS: Surgical resection was performed on the patient.
      OUTCOMES: Histopathological examination demonstrated that the mass was a
      retroperitoneal bronchogenic cyst. At the 2-month postoperative follow-up, the
      level of CA 19-9 had returned to normal. LESSONS: EUS appears to be superior to
      CT because it clearly delineated the mass from the surrounding structures of the
      retroperitoneal region. EUS-fine needle aspiration can be used for diagnosis or
      determining whether the mass is malignant or benign. To the best of our
      knowledge, retroperitoneal bronchogenic cysts with significantly elevated serum
      CA 19-9 have not been reported. Measurement of serum CA 19-9 may be helpful in
      the diagnosis of retroperitoneal bronchogenic cysts. However, this was a rare
      case, and the mechanism behind CA 19-9 elevation is not clear and needs further
      investigation.

PMID- 28767595
TI  - The comparison of measurement between ultrasound and computed tomography for
      abnormal degenerative facet joints: A STROBE-compliant article.
AB  - Besides the study on examining facet joints of lumbar spine by ultrasound in
      normal population, there has not been any related report about examining normal
      facet joints of lumbar spine by ultrasound so far. This study was aimed to
      explore the feasibility of ultrasound assessment of lumber spine facet joints by
      comparing ultrasound measure values of normal and degenerative lumber spine facet
      joints, and by comparing measure values of ultrasound and computed tomography
      (CT) of degenerative lumber spine facet joints.This study included 15 patients
      who had chronic low back pain because of degenerative change in lumbar vertebrae,
      and 19 volunteers who did not have low back pain or pain in the lower limb. The
      ultrasound measure values (height [H] and width [W]) of normal and degenerative
      lumber spine facet joints were compared. And the differentiation between measure
      values (H and W) of ultrasound and CT of degenerative lumber spine facet joints
      was also analyzed.The ultrasound clearly showed abnormal facet joints lesion,
      which was characterized by hyperostosis on the edge of joints, bone destruction
      under joints, and thinner or thicker articular cartilage. There were significant
      differences between the ultrasound measure values of the normal (H: 1.26 +/- 0.03
      cm, W: 0.18 +/- 0.01 cm) and abnormal facet joints (H: 1.43 +/- 0.05 cm, W: 0.15
      +/- 0.02 cm) (all P < .05). However, there were no significant differences
      between the measure values of the ultrasound (H: 1.43 +/- 0.17 cm, W: 0.15 +/-
      0.03 cm) and CT (H: 1.42 +/- 0.16, W: 0.14 +/- 0.03) of the degenerative lumber
      spine facet joints (all P > .05).Ultrasound can clearly show the structure of
      facet joints of lumbar spine. It is precise and feasible to assess facet joints
      of lumbar spine by ultrasound. This study has important significance for the
      diagnosis of lumbar facet joint degeneration.

PMID- 28767596
TI  - Duodenum-derived fibromatosis that invaded the muscular layer of intestinal wall:
      A rare case report.
AB  - RATIONALE: Intraabdominal fibromatosis is a rare benign tumor that often affects
      the mesentery or retroperitoneum, and can infiltrate adjacent organs. However, it
      is rare for fibromatosis to arise from the small intestinal wall. PATIENT
      CONCERNS: A 27-year-old female with a tangible abdominal tumor is described.
      DIAGNOSES: The computed tomography (CT) scan revealed a 7.5 cm, small intestine
      associated tumor in the right abdomen. INTERVENTIONS: The patient received tumor
      resection and intestinal anastomosis. OUTCOMES: Further pathological examination
      confirmed the tumor as a duodenal fibromatosis that infiltrated the intestinal
      wall. To the best of our knowledge, this is the first report of a duodenum
      derived fibromatosis that invaded the muscular layer of the intestine. LESSONS:
      Our study demonstrated that an unexplained abdominal mass should be noteworthy
      and properly treated.

PMID- 28767597
TI  - Comparison of IMRT versus 3D-CRT in the treatment of esophagus cancer: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Esophageal cancer (EC) is a common cancer with high mortality because
      of its rapid progression and poor prognosis. Radiotherapy is one of the most
      effective treatments for EC. Three-dimensional conformal radiotherapy (3D-CRT)
      and intensity-modulated radiotherapy (IMRT) are 2 recently developed radiotherapy
      techniques. IMRT is believed to be more effective than 3D-CRT in target coverage,
      dose homogeneity, and reducing toxicity to normal organs. However, these
      advantages have not been demonstrated in the treatment of EC. This meta-analysis
      was performed to compare IMRT and 3D-CRT in the treatment of EC in terms of dose
      volume histograms and outcomes including survival and toxicity. METHODS: A
      literature search was performed in PubMed, Embase, and the Cochrane library
      databases from their inceptions to Dec 30, 2016. Two authors independently
      assessed the included studies and extracted data. The average percent irradiated
      volumes of adjacent noncancerous organs were calculated and compared between IMRT
      and 3D-CRT. The odds ratio of overall survival (OS), and radiation pneumonitis
      and radiation esophagitis was also evaluated. RESULTS: Totally 7 studies were
      included. Of them, 5 studies (80 patients) were included in the dosimetric
      comparison, 3 studies (871 patients) were included in the OS analysis, and 2
      studies (205 patients) were included in the irradiation toxicity analysis. For
      lung in patients receiving doses >=20 Gy and heart in patients receiving dose =
      50 Gy, the average irradiated volumes of IMRT were less than those from 3D-CRT.
      IMRT resulted in a higher OS than 3D-CRT. However, no significant difference was
      observed in the incidence of radiation pneumonitis and radiation esophagitis
      between 2 radiotherapy techniques. CONCLUSION: Our data suggest that IMRT
      delivered high radiation dose produces significantly less average percent volumes
      of irradiated lung and heart than 3D-CRT. IMRT is superior to 3D-CRT in the OS of
      EC while shows no benefit on radiation toxicity.

PMID- 28767598
TI  - Giant liver hemangioma with adult Kasabach-Merritt syndrome: Case report and
      literature review.
AB  - RATIONALE: Adult Kasabach-Merritt syndrome associated with giant liver hemangioma
      is rare; to date, most reports have been single-case reports, and no multi-case
      reports or literature reviews are available. DIAGNOSES: We conducted a
      retrospective analysis of 5 cases of adult Kasabach-Merritt syndrome associated
      with giant liver hemangioma treated at our hospital between 2011 and 2016. All 5
      patients had varying severities of leukopenia, anemia, thrombocytopenia,
      prolonged prothrombin time, and hypofibrinogenemia. INTERVENTIONS: All the
      patients underwent surgery: 2 patients had left hemihepatectomy; 1 had
      enucleation; 1 had a right hemihepatectomy; and 1 had a left trisectionectomy.
      OUTCOMES: The 5 patients had an average operative time of 6.9 hours and an
      average blood loss of 3200 mL. One patient developed a biliary fistula (grade II)
      after the operation. There was no mortality among 5 patients. The white blood
      cell counts, hemoglobin, platelets, and prothrombin times of all 5 patients
      returned to normal after the operation. To date, a total of 11 cases of adult
      Kasabach-Merritt syndrome associated with giant liver hemangioma have been
      reported, of which 8 patients underwent surgery, and their platelets and
      coagulation returned to normal after the operation. LESSONS: Adult Kasabach
      Merritt syndrome associated with giant liver hemangioma is uncommon, and surgical
      treatment is risky. However, resection of the tumor corrected the abnormalities
      in hematological and coagulative systems.

PMID- 28767599
TI  - Investigation of the status quo of massive blood transfusion in China and a
      synopsis of the proposed guidelines for massive blood transfusion.
AB  - The aim of this study was to provide an overview of massive transfusion in
      Chinese hospitals, identify the important indications for massive transfusion and
      corrective therapies based on clinical evidence and supporting experimental
      studies, and propose guidelines for the management of massive transfusion. This
      multiregion, multicenter retrospective study involved a Massive Blood Transfusion
      Coordination Group composed of 50 clinical experts specializing in blood
      transfusion, cardiac surgery, anesthesiology, obstetrics, general surgery, and
      medical statistics from 20 tertiary general hospitals across 5 regions in China.
      Data were collected for all patients who received >=10 U red blood cell
      transfusion within 24 hours in the participating hospitals from January 1 2009 to
      December 31 2010, including patient demographics, pre-, peri-, and post-operative
      clinical characteristics, laboratory test results before, during, and after
      transfusion, and patient mortality at post-transfusion and discharge. We also
      designed an in vitro hemodilution model to investigate the changes of blood
      coagulation indices during massive transfusion and the correction of coagulopathy
      through supplement blood components under different hemodilutions. The
      experimental data in combination with the clinical evidence were used to
      determine the optimal proportion and timing for blood component supplementation
      during massive transfusion. Based on the findings from the present study,
      together with an extensive review of domestic and international transfusion
      related literature and consensus feedback from the 50 experts, we drafted the
      guidelines on massive blood transfusion that will help Chinese hospitals to
      develop standardized protocols for massive blood transfusion.

PMID- 28767600
TI  - MECP2 expression in gastric cancer and its correlation with clinical pathological
      parameters.
AB  - This study is to investigate the expression of methyl CpG binding protein 2
      (MECP2) in gastric cancer (GC) and its clinical significance.Expression of MECP2
      was analyzed in 69 cases of GC tissues and 12 paracancerous tissues, either by
      qRT-PCR at the mRNA level or by Western blot and immunochemistry at the protein
      level. The correlation of MECP2 expression with clinicopathological parameters
      was analyzed in the 69 GC patients, and validated in data from the TCGA database.
      The effect of MECP2 expression on survival was also investigated.MECP2 was
      significantly increased at both mRNA and protein levels in GC compared with
      paracancerous tissues. MECP2 positive expression was significantly correlated
      with the TNM stages, histological types, and lymph node metastasis status, but
      was not correlated with sex or age. Significantly shorter overall survival and
      disease-free survival was observed in MECP2 positive GC cases compared with the
      MECP2 negative cases. Univariate and multivariate analyses showed that gender,
      histological type, lymph node metastasis, and MECP2 expression were independent
      prognostic factors of GC.The dysregulated expression of MECP2 in GC and its
      correlation to clinicopathological parameters indicate that MECP2 may regulate
      the development of GC.

PMID- 28767601
TI  - Validation and reliability of Falls Risk for Hospitalized Older People (FRHOP):
      Taiwan version.
AB  - A comprehensive fall risk assessment can provide information for effective
      prevention and intervention measures and reduce falls among hospitalized elderly
      people. The purpose of this study was to develop a Chinese version of an
      inpatient fall risk assessment tool and evaluate its validity and
      reliability.This study employed the Falls Risk for Hospitalised Older People
      (FRHOP) assessment to construct a FRHOP-Taiwan Version (Tw-FRHOP) through
      forward, synthesized, and backward translation. A face validation was conducted
      by 5 clinical nurses and a content validation was conducted by 5 specialists
      using the content validity index (CVI) to validate the proposed model. Thirty
      hospitalized older adults in an internal care unit were selected for an
      interrater reliability assessment, conducted separately by specialists in 4
      disciplines (i.e., nurses, physicians, occupational therapists, and
      physiotherapists) by using Cohen kappa statistic and intraclass correlation
      coefficients (ICCs). Specifically, the assessment rating developed in the Tw
      FRHOP was compared with the Morse Fall Scale (MFS), St. Thomas Risk Assessment
      Tool in Falling Elderly Inpatients (STRATIFY), and the Hendrich II Fall Risk
      Model (HIIFRM) for criterion validation.According to the analysis results, the
      CVI was 0.94, and the indexes of criterion-related validity for the FRHOP-Taiwan
      Version, MFS, STRATIFY, and HIIFRM were 0.49, 0.63, and 0.54 (all P < .001),
      respectively. In addition, after interrater reliability testing was conducted,
      the results indicated that the index of response consistency in each discipline
      was 86.7% to 100%, and the values of Cohen kappa were 0.651 to 1.000. The ICCs of
      the discipline-related subscale were 0.97 to 1.00.The Tw-FRHOP is a
      multidisciplinary comprehensive fall risk assessment that can serve as a
      satisfactorily valid and reliable reference tool for medical personnel with full
      professional training, as well as inpatient fall prevention interventions for
      multidisciplinary teams in hospitals.

PMID- 28767602
TI  - Iatrogenic rupture of the left main bronchus secondary to repeated surgical lobe
      torsion during double-lumen tube placement: A case report.
AB  - RATIONALE: Bronchial rupture is a rare but potentially life-threatening
      complication during double-lumen endobronchial tube placement. The rupture of the
      left main bronchus resulting from repeated surgical torsion is uncommon. PATIENT
      CONCERNS: A 70-year-old man with a history of chronic obstructive pulmonary
      disease (COPD), intermediate emphysema, chronic bronchitis, hypertension, type 2
      diabetes mellitus, and L3-L4 lumbar intervertebral disc herniation. Chest x-ray
      and computed tomography revealed a solitary pulmonary nodule in the left lower
      lobe. DIAGNOSES: Left lower lobe carcinoma. INTERVENTIONS: To improve surgical
      access, forceps were used to oppress and torque the left lung. OUTCOMES: An
      irregular, circular, horizontal, full-thickness rupture of 1.2 cm was observed at
      the tip of the bronchial tube in the left main bronchus upon examination of the
      bronchial stump.The rupture was repaired via primary suturing with 4-0 prolene
      thread and secondary reinforcement with a pericardial flap through a left
      thoracotomy, with no further complications. LESSONS: Caution should be exercised
      during compression and torsion of the pulmonary lobe when attempting to improve
      surgical access, especially in patients with COPD. Conversion to thoracotomy is
      recommended if other measures have been unsuccessful.

PMID- 28767603
TI  - Individual and health system variation in rehospitalizations the year after
      pneumonia.
AB  - Little is known about variation in patterns of recovery among patients discharged
      alive from hospitalizations for pneumonia.The aim of the is observational cohort
      study was to characterize the variation in patterns of hospital readmission and
      survival in the year after discharge for pneumonia in 3 different health
      systems.The 3 cohorts consisted of (1) the Health and Retirement Study
      participants enrolled in Fee-for-service Medicare (FFS), (2) Veterans
      Administration (VA) Healthcare system, and (3) Kaiser Permanente of Northern
      California (KPNC). The 365-day survival and re-hospitalizations were determined
      for each cohort. Multinomial logistic regression was used to identify potential
      contributors to the different patterns.We identified 2731, 23,536, and 39,147
      hospitalizations for pneumonia in FFS Medicare, VA, and KPNC, respectively, of
      whom 88.1%, 92.8%, and 89.7% survived to hospital discharge. The median patient
      survived to 1 year and was rehospitalized twice in FFS (9.0%), once in VA (14.1%)
      and KPNC (9.1%). Of the patients who survived the hospitalization, 33.3% (FFS),
      30.2% (VA), and 26.8% (KPNC) died during the subsequent year. Of those who
      survived, 29.8% (FFS), 35.9% (VA), and 46.1% (KPNC) were never rehospitalized.
      11.9% (FFS), 11.9% (VA), and 11.7% (KPNC) had greater than 3 hospitalizations.
      Age, race, gender, comorbidity, ICU use, and hospital length stay collectively
      explained little (5-7%) of the variation in the recovery pattern.There is
      significant variation in the year after the hospitalization for pneumonia across
      individuals, but less so across health systems. There may be important
      opportunities to better classify these heterogeneous individual-level pathways.

PMID- 28767604
TI  - Serum 25-hydroxyvitamin D might be an independent prognostic factor for Graves
      disease recurrence.
AB  - Graves disease is the most common cause of thyrotoxicosis. Although medical
      intervention with antithyroid drugs (ATDs) is commonly the first choice of
      treatment in Korea, the remission rate associated with this approach is not
      satisfactory. During ATD therapy, low or undetectable serum levels of thyroid
      stimulating hormone (TSH) receptor antibodies (TRAbs) have been reported to
      affect the incidence of Graves disease remission. This study evaluated the
      correlation between serum 25-hydroxyvitamin D levels and TRAb levels, as well as
      the effect of 25-hydroxyvitamin D on the recurrence of Graves disease.A total of
      143 patients, who were diagnosed with Graves disease and treated with ATDs, were
      retrospectively included in our observational study. These patients were followed
      for more than 1 year after ATD discontinuation. The levels of serum 25
      hydroxyvitamin D and TRAb (ie, thyroid-stimulating antibody [TSAb], as detected
      by bioassay, and TSH-binding inhibitory immunoglobulins [TBIIs]) were measured,
      and a thyroid function test was performed upon ATD discontinuation. Recurrence
      was evaluated every 3 months, and was defined as an occurrence of overt
      thyrotoxicosis during the follow-up period.A total of 95 patients (66.4%)
      experienced recurrence with a median latency period of 182 days (ranging 28-1219
      days). The serum 25-hydroxyvitamin D levels at the time of ATD discontinuation
      were not correlated with either TBII or TSAb. In the Cox proportional hazard
      regression analysis, higher free T4 levels (>1.4 ng/dL; hazard ratio [HR], 3.252;
      95% confidence interval [CI], 1.022-10.347) and low levels of 25-hydroxyvitamin D
      (<=14.23 ng/mL) were associated with a higher probability of Graves disease
      recurrence (HR, 3.016; 95% CI, 1.163-7.819).Lower serum 25-hydroxyvitamin D
      levels were associated with a higher incidence of Graves disease recurrence.
      Therefore, serum 25-hydroxyvitamin D might be an independent risk factor for
      predicting Graves disease recurrence after ATD discontinuation.

PMID- 28767605
TI  - A case report of intraventricular tigecycline therapy for intracranial infection
      with extremely drug resistant Acinetobacter baumannii.
AB  - RATIONALE: Intracranial infection with Acinetobacter baumannii is a tough problem
      due to the presence of multiresistance and drugs poor penetration through the
      blood brain barrier (BBB). Tigecycline is effective to cure A baumannii, but it
      can only be used intravenously which is also difficult to pass BBB. So, it will
      be a breakthrough if intraventricular (IVT) tigecycline is used in the clinical
      therapy. However, this treatment has been reported quite rarely until now.
      PATIENT CONCERNS: We described a case of a 50-year-old male worker whose clinical
      futures were high fever and cerebral rigidity after neurosurgery. DIAGNOSES:
      Intracranial infection with extensive drug resistant (XDR) A baumannii.
      INTERVENTIONS: The patient was treated with IVT tigecycline. OUTCOMES: The
      symptoms of intracranial infection disappeared. The temperature of this patient
      decreased to normal and cerebral rigidity disappeared. The cerebrospinal fluid
      culture became negative, with normal levels of white blood cell, glucose and
      chlorine. LESSONS: IVT tigecycline therapy maybe effective to intracranial
      infection with XDR A baumannii. However, more studies will further demonstrate
      the therapeutic values of IVT tigecycline to intracranial infection, and not only
      restricted to A baumannii infections.

PMID- 28767606
TI  - Varicoceles affect semen quality of infertile men in Southern China: A cross
      sectional study of 5447 cases.
AB  - The association of varicoceles with infertility is well established, but the
      exact effect of varicoceles on semen quality among patients with infertility is
      still poorly known. The study aimed to examine the prevalence of varicoceles
      among Chinese men with infertility and to examine the factors associated with
      semen quality.This was a cross-sectional study of 5447 male patients treated for
      infertility at the Affiliated Hospital of Guangdong Medical University from
      October 2012 to December 2015. The patients were divided on the basis of the
      presence of varicoceles. Examinations of the amount of semen and sperm morphology
      were performed according to seminal parameter detection methods recommended by
      the World Health Organization.Patients with varicoceles (n = 1429/5447, 26.2%)
      were slightly younger (P = .046), and had smaller testis (P = .019), higher
      frequency of abnormal epididymis (P < .001), slightly shorter infertility
      duration (P = .046), and lower frequency of smokers (P = .012). There was no
      difference in the distribution of occupations (P = .777). Using multiple linear
      regression analysis, varicoceles were shown to be independently associated with
      semen volume [B = -0.153, 95% confidence interval (95% CI): -0.245 to -0.062, P =
      .001], sperm concentration (B = 9.633, 95% CI: 7.152-12.114, P < .001),
      proportion of sperms with normal morphology (B = 0.951, 95% CI: 0.623-1.278, P <
      .001), motility (B = 3.835, 95% CI: 2.675, 4.995, P < .001), total sperm count (B
      = 22.481, 95% CI: 13.333-31.629, P < .001), and forward movement sperm count (B =
      15.553, 95% CI: 9.777-21.329, P < .001). Varicoceles were present in 26% of
      Chinese male patients with infertility.Varicoceles were independently associated
      with sperm volume, sperm concentration, proportion of sperms with normal
      morphology, motility, total sperm count, and forward movement sperm count.

PMID- 28767607
TI  - Primary clear cell carcinoma of the trachea: A CARE-compliant case report.
AB  - RATIONALE: Primary clear cell carcinoma of the lung is a rare condition, and
      presentation as an endotracheal lesion is even more unusual. In this report, we
      present a patient with clear cell carcinoma occurring in the trachea, which
      obstructed the tracheal lumen and lead to the respiratory distress. PATIENT
      CONCERNS: A 60-year old female patient was admitted due to a 6-month history of
      dyspnea with worsening symptoms for 1 month. Chest CT scan revealed a smooth
      nodular shadow with homogeneous density on the wall of upper trachea. DIAGNOSIS:
      Bronchoscopy therapy and surgical removal of the tumor were performed. The
      histopathological diagnosis revealed clear cell carcinoma. INTERVENTION: Surgical
      removal of the clear cell carcinoma was performed. OUTCOMES: The patient
      recovered well after the surgery and is now being followed-up after hospital
      discharge. LESSONS: Bronchoscopy is an essential tool for diagnosis of tracheal
      clear cell carcinoma. Surgical removal should be performed if possible.

PMID- 28767608
TI  - Carotid intima-media thickness is a novel predictor of new onset of hypertension
      in normotensive subjects.
AB  - Increased carotid intima-media thickness (IMT) in individuals without
      hypertension might indicate other factors promoting the atherosclerotic process
      that are often simultaneously clustered in individuals. The present study tested
      the hypothesis that carotid IMT predicts new onset of hypertension in the
      normotensive subjects.A total of 867 participants were enrolled from our yearly
      physical checkup program and their carotid IMT was measured. After a baseline
      examination, the subjects were followed up for a median of 1091 days with the
      endpoint being the development of hypertension.At baseline, the carotid IMT value
      was 0.75 +/- 0.16 mm. Hypertension developed in 184 subjects during the follow-up
      (76.9/1000 person-years). The incidence of hypertension was increased across the
      tertiles of the carotid IMT value (39.6, 70.0, and 134.5/1000 person-years in the
      first, second, and third tertiles, respectively, P < .001 by log-rank test).
      Multivariate Cox-hazard analysis after adjustment identified carotid IMT, taken
      as a continuous variable, as a significant predictor of new-onset hypertension
      (hazard ratio = 7.08, 95% confidence interval = 3.06-15.39). Furthermore,
      multivariate linear regression analyses indicated a significant correlation
      between the carotid IMT at baseline and yearly increases in systolic blood
      pressure during the follow-up period (beta = 0.189, P < .001).Carotid IMT is an
      independent predictor of hypertension onset in normotensive subjects. The
      findings also suggested a close association between increased carotid IMT and
      blood pressure.

PMID- 28767609
TI  - Sinonasal renal cell-like adenocarcinoma, a unique variant of primary clear cell
      carcinoma of the head and neck: The first reported case in Korea.
AB  - RATIONALE: Primary sinonasal renal cell-like adenocarcinoma (SNRCLA) is a rare
      and unique neoplasm. PATIENT CONCERNS: A 63-year-old man presented with repeated
      epistaxis, nasal obstruction and hyposmia of 2-month duration. Radiological
      studies revealed a mass of the left ethmoid sinus involving anterior skull base.
      DIAGNOSIS: The patient was treated with craniofacial resection, bifrontal
      craniotomy combined with an endonasal endoscopic approach. Intraoperatively, a
      hypervascular paranasal mass invading the dura mater was removed en block.
      Histologically, the tumor resembled a clear cell renal cell carcinoma, with
      cuboidal shaped cells having clear cytoplasm. The tumor cells were positive for
      CK7, S100, vimentin and PAX-8 and negative for CD10 and PAX-2 by
      immunohistochemistry. No evidence of renal malignancy was found by radiological
      and clinical examinations. INTERVENTIONS AND OUTCOMES: Following local radiation
      therapy, the patient was in good health without recurrence for 15 months after
      the operation. LESSONS: To the best of the authors' knowledge, this is the first
      reported case of SNRCLA in Korea. Because of its histological feature of clear
      cytoplasm, SNRCLA needs to be differentiated from clear cell renal cell carcinoma
      and other salivary clear cell carcinomas. The prognosis of SNRCLA is generally
      favorable as shown in the previously reported cases. Considering the limited
      number and follow-up periods of the cases, however, delayed recurrence should be
      kept in mind for clinicians.

PMID- 28767610
TI  - Clinicopathological features, surgical treatments, and survival outcomes of
      patients with small bowel adenocarcinoma.
AB  - To date, because of their rarity, the clinicopathological features and surgical
      outcomes of small bowel adenocarcinomas (SBAs) have been insufficiently explored.
      We evaluated the clinicopathological features and long-term outcomes of patients
      who underwent surgery for SBA.This retrospective study (from 1999 to 2016)
      examined patients with SBA treated surgically at the China National Cancer
      Center/Cancer Hospital. Clinicopathological features, preoperative evaluation,
      surgical treatment, and outcome parameters were reviewed and analyzed.Among the
      241 patients studied, pancreaticoduodenectomies were performed in 51.0%, partial
      resection in 24.5%, palliative bypass surgery in 23.7%, and abdominal exploration
      in 0.8% of the patients. Majority of the patients were diagnosed at an advanced
      disease stage, and the duodenum was the most common tumor site. Postoperative
      complications occurred in 44.4% of the patients. Median overall and progression
      free survival rates were 22.0 and 13.0 months, respectively. The 5-year overall
      and progression-free survival rates for patients with duodenal adenocarcinoma
      were 30.2% and 21.7%, respectively. Duodenal adenocarcinomas, lymph node
      metastases, distant metastases, poor differentiation, and lymphovascular invasion
      were associated with poor overall survival outcomes. The 3 factors associated
      with progression-free survival were the degree of differentiation, lymph node
      metastases, and distant metastases.Surgery remains the mainstay of treatment for
      SBA. A poor prognosis could be owing to the site, metastasis, differentiation,
      and lymphovascular invasion; however, the prognosis may improve through early
      diagnosis and operation.

PMID- 28767611
TI  - Pregabalin can decrease acute pain and postoperative nausea and vomiting in
      hysterectomy: A meta-analysis.
AB  - BACKGROUND: Whether the preoperative administration of pregabalin plays a
      beneficial role in controlling acute pain after hysterectomy is unknown. We
      performed a systematic review and meta-analysis of randomized controlled trials
      (RCTs) to determine the efficacy and safety of the preoperative use of pregabalin
      to treat acute postoperative pain following hysterectomy. METHODS: In April 2017,
      a systematic computer-based search was conducted in the PubMed, EMBASE, Web of
      Science, Cochrane Library, and Google databases. RCTs comparing pregabalin with
      placebo in patients undergoing hysterectomy were retrieved. The primary endpoint
      was the visual analog scale (VAS) score with rest or mobilization at 2 h, 4 and
      24 hours and cumulative morphine consumption at 2, 4, 24, and 48 hours. The
      secondary outcomes were complications of nausea, vomiting, sedation, and
      dizziness. After tests for publication bias and heterogeneity among studies were
      performed, the data were aggregated for random-effects models when necessary.
      RESULTS: Ten clinical studies with 1207 patients (pregabalin = 760, control =
      447) were finally included in this meta-analysis. Preoperative administration of
      pregabalin was associated with a significant reduction of VAS with rest or
      mobilization at 2, 4, and 24 hours after hysterectomy. Further, the preoperative
      administration of pregabalin was associated with a reduction in total morphine
      consumption at 2, 4, 24, and 48 hours after hysterectomy. The occurrence of
      morphine-related complications (nausea and vomiting) was also reduced in the
      pregabalin group. However, the preoperative administration of pregabalin was
      associated with an increase in the occurrence of dizziness. There was no
      significant difference in the occurrence of sedation. CONCLUSIONS: The
      preoperative use of pregabalin reduced postoperative pain, total morphine
      consumption, and morphine-related complications following hysterectomy. The doses
      of pregabalin were different, and large heterogeneity was the limitation of the
      current meta-analysis. Further studies should determine the optimal dose for
      controlling acute pain after hysterectomy.

PMID- 28767612
TI  - Pyoderma gangrenosum in a patient with chronic granulomatous disease: A case
      report.
AB  - RATIONALE: The simultaneous occurrence of pyoderma gangrenosum (PG) and chronic
      granulomatous disease (CGD) is uncommon and few cases have been reported
      worldwide. PATIENT CONCERNS: PG is a rare, chronic, ulcerative, neutrophilic skin
      disease of unknown etiology that requires immunosuppressive treatment. CGD
      belongs to Primary Immune Deficiencies in which the main defect lies in an
      inability of the phagocytic cells to generate superoxide making patients
      susceptible to serious, potentially life-threatening bacterial and fungal
      infections. DIAGNOSES: In this manuscript, we present a case of ulcerative
      pyoderma gangrenosum in a 28-year-old man with recent diagnosis of chronic
      granulomatous disease during hospitalization for resistant pulmonary tuberculosis
      complicated with Aspergillus infection. INTERVENTIONS: Second-line therapy with
      dapsone and intravenous immunoglobulin was initially administered but eventually
      corticosteroids were added to treatment because of disease progression and
      further ulceration. OUTCOMES: Patient's ulcers were gradually healed with no side
      effects. LESSONS: Corticosteroids could be used under close monitoring for the
      treatment of PG in a patient with CGD, despite the increased risk for infections.

PMID- 28767613
TI  - Effect of greater trochanteric epiphysiodesis after femoral varus osteotomy for
      lateral pillar classification B and B/C border Legg-Calve-Perthes disease: A
      retrospective observational study.
AB  - This is a retrospective observational study. Greater trochanteric epiphysiodesis
      (GTE) has been recommended to prevent Trendelenburg gait and limitation of the
      hip joint motion due to trochanteric overgrowth after femoral varus osteotomy
      (FVO) in Legg-Calve-Perthes disease (LCPD). However, capital femoral physeal
      arrest frequently occurs in patients with severe disease (lateral pillar C), so
      GTE might not be as effective in these patients. The aim of this study was to
      compare trochanteric growth inhibition due to GTE after FVO between 2 age groups
      (<8 or >8 years) in patients with lateral pillar B and B/C border LCPD and
      evaluate the effectiveness of GTE compared with the normal, unaffected hip.This
      study included 19 children with lateral pillar B and B/C border LCPD in 1 leg who
      underwent FVO followed by GTE. Of the 19 children, 9 underwent GTE before the age
      of 8 years and 10 underwent GTE after 8 years of age. On radiographs taken at the
      immediate postoperative period and at skeletal maturity, the articulo
      trochanteric distance (ATD), center-trochanteric distance (CTD), and neck-shaft
      angle (NSA) were compared between the 2 age groups. The amount of correction was
      compared between groups. The contralateral, unaffected hip was used as a control
      for trochanteric growth. The patients were clinically evaluated with Iowa hip
      score at the final follow-up.There was no significant difference between the 2
      age groups in terms of time to GTE, length of follow-up, or lateral pillar
      classification. In the affected hip, the amount of correction of the ATD, CTD,
      and NSA was significantly greater in patients < 8 years than in patients > 8
      years. However, in the unaffected hip, the change in the ATD, CTD, and NSA did
      not differ significantly between the 2 groups.We suggest that FVO followed by GTE
      for lateral pillar B and B/C border LCPD in patients under the age of 8 years can
      affect growth of the greater trochanter. However, effective growth inhibition due
      to GTE was not achieved after 8 years of age.

PMID- 28767614
TI  - Primary intestinal lymphangiectasia in an elderly female patient: A case report
      on a rare cause of secondary immunodeficiency.
AB  - Protein loss via the gut can be caused by a number of gastrointestinal disorders,
      among which intestinal lymphangiectasia has been described to not only lead to a
      loss of proteins but also to a loss of lymphocytes, resembling secondary
      immunodeficiency. We are reporting on a 75-year-old female patient who came to
      our hospital because of a minor stroke. She had no history of serious infections.
      During the diagnostic work-up, we detected an apparent immunodeficiency syndrome
      associated with primary intestinal lymphangiectasia. Trying to characterize the
      alterations of the immune system, we not only found hypogammaglobulinemia and
      lymphopenia primarily affecting CD4+, and also CD8+ T cells, but also marked
      hypocomplementemia affecting levels of complement C4, C2, and C3. The loss of
      components of the immune system most likely was due to a chronic loss of immune
      cells and proteins via the intestinal lymphangiectasia, with levels of complement
      components following the pattern of protein electrophoresis. Thus, intestinal
      lymphangiectasia should not only be considered as a potential cause of secondary
      immune defects in an elderly patient, but can also be associated with additional
      hypocomplementemia.

PMID- 28767615
TI  - Imported Schistosomiasis in Children: Clinical, Diagnostic Aspects And Outcome in
      5 Tertiary Hospitals in France.
AB  - The objective of this retrospective study is to describe imported schistosomiasis
      in children in the Paris region between 2010 and 2015. Forty children with a
      diagnosis of schistosomiasis were included. Thirty-seven (93%) had a chronic
      urinary form with hematuria. The lost-to-follow up rate for the second
      consultation was 25%. The diagnosis and management of imported schistosomiasis
      must be improved-notably by raising awareness among clinicians and providing
      families with more information.

PMID- 28767617
TI  - Prevalence of Group B Streptococcus in Pregnant Women in Iran: A Systematic
      Review and Meta-analysis.
AB  - BACKGROUND: Group B Streptococcus (GBS or S. agalactiae) is a major cause of
      severe disease in neonates. In perinatal infections or early-onset disease, GBS
      is transmitted vertically to the newborn from the birth canal during labor and
      delivery. Limited information is available on the prevalence of GBS recto-vaginal
      colonization among pregnant women in Iran. METHODS: We performed a systematic
      search by using different electronic databases including Medline (via Pubmed),
      Embase, Web of Science and Iranian Database. Meta-analysis was performed by
      Comprehensive Meta-Analysis (Biostat V2.2) software. RESULTS: Of 250 articles
      published from January 2000 to September 2016, 25 studies that reported incidence
      of GBS colonization in pregnant women were included in this review. The meta
      analyses showed that the prevalence of GBS colonization among Iranian pregnant
      women was 9.8% (95% confidence interval, 7.9-12). CONCLUSIONS: The results of
      this study indicate that GBS screening measures and chemoprophylaxis guidelines
      concerning GBS infections must be established for pregnant women in Iran, and
      these guidelines must provide guidance for obstetricians, midwives and
      neonatologists on the prevention of GBS infections.

PMID- 28767616
TI  - Impact of Birth HIV-PCR Testing on the Uptake of Follow-up Early Infant Diagnosis
      Services in Cape Town, South Africa.
AB  - INTRODUCTION: Polymerase chain reaction testing at birth ("birth-testing") is
      suggested by new World Health Organization guidelines for rapid diagnosis of
      infants infected with HIV in utero. However, there are few data on the
      implementation of this approach in sub-Saharan Africa, and whether birth testing
      affects uptake of subsequent routine early infant diagnosis (EID) testing at 6-10
      weeks of age is unknown. METHODS: We reviewed 575 consecutive infants undergoing
      targeted high-risk birth testing in Cape Town, South Africa, and matched those
      testing HIV negative at birth (n = 551) to HIV-exposed infants who did not
      receive birth testing (n = 551). Maternal and infant clinical and demographic
      data, including EID testing uptake, were abstracted from routine records.
      RESULTS: Overall, 3.8% of all birth tests conducted were positive while later EID
      testing positivity rates were 0.5% for those infants testing HIV negative at
      birth and 0.4% for those without birth testing. Infants who underwent birth
      testing were less likely to present for later EID compared with those without a
      birth test (73% vs. 85%; P < 0.001). This difference persisted after adjusting
      for maternal and infant characteristics (adjusted odds ratio, 0.60; 95%
      confidence interval: 0.41-0.86) and across demographic and clinical subgroups.
      Infants undergoing birth testing also presented for later EID at a significantly
      older age (mean age, 60 vs. 50 days; P < 0.001). CONCLUSIONS: While the yield of
      targeted high-risk birth testing in this setting appears high, neonates testing
      HIV negative at birth may be less likely to present for subsequent EID testing.
      For birth testing implementation to contribute to overall EID program goals,
      structured interventions are required to support follow-up EID services after
      negative birth test results.

PMID- 28767618
TI  - Probiotics for Modification of the Incidence or Severity of Respiratory Tract
      Infections.
AB  - There is increasing interest in probiotics for therapy and prevention of
      infectious diseases. There are no published trials of probiotics as therapy for
      respiratory tract infections (RTIs) in children or adults. There is low quality,
      inconsistent evidence for the efficacy of probiotics for prevention of RTIs or
      ventilator-associated pneumonia or for modification of the severity of RTIs.

PMID- 28767619
TI  - Women Administered Standard Dose Imatinib for Chronic Myeloid Leukemia Have
      Higher Dose-Adjusted Plasma Imatinib and Norimatinib Concentrations Than Men.
AB  - BACKGROUND: The standard dose of imatinib for the treatment of chronic-phase
      chronic myeloid leukemia (CML) is 400 mg.d. A predose plasma imatinib
      concentration of >1 mg.L is associated with improved clinical response. This
      study aimed to assess the plasma imatinib and norimatinib concentrations attained
      in patients with chronic myeloid leukemia administered standard doses of imatinib
      adjusted for dose, age, sex, body weight, and response. METHODS: We evaluated
      data from a cohort of patients treated between 2008 and 2014 with respect to
      dose, age, sex, body weight, and response. RESULTS: The study comprised 438
      samples from 93 patients (54 male, 39 female). The median imatinib dose was 400
      mg.d in men and in women. The plasma imatinib concentration ranged 0.1-5.0 mg.L
      and was below 1 mg.L in 20% and 16% of samples from men and women, respectively.
      The mean dose normalized plasma imatinib and norimatinib concentrations were
      significantly higher in women in comparison with men. This was partially related
      to body weight. Mixed effects ordinal logistic regression showed no evidence of
      an association between sex and plasma imatinib (P = 0.13). However, there was
      evidence of an association between sex and plasma norimatinib, with higher
      norimatinib concentrations more likely in women than in men (P = 0.02).
      CONCLUSIONS: Imatinib therapeutic drug monitoring only provides information on
      dosage adequacy and on short-term adherence; longer-term adherence cannot be
      assessed. However, this analysis revealed that approximately 1 in 5 samples had a
      plasma imatinib concentration <1 mg.L, which was suggestive of inadequate dosage
      and/or poor adherence and posed a risk of treatment failure. Higher imatinib
      exposure in women may be a factor in the increased rate of long-term, stable,
      deep molecular response (undetectable breakpoint cluster-Abelson (BCR-ABL)
      transcript levels with a PCR sensitivity of 4.5 log, MR4.5) reported in women.

PMID- 28767620
TI  - Effects of Training and Overtraining on Intervertebral Disc Proteoglycans.
AB  - STUDY DESIGN: Animal experimental study. OBJECTIVE: Evaluate the effect of
      physical activity and overtraining condition on glycosaminoglycan concentration
      on the intervertebral disc (IVD) using a rat running model. SUMMARY OF BACKGROUND
      DATA: Some guidelines recommend the implementation of a physical exercise program
      as treatment for low back pain; however, cyclic loading impact on the health of
      the IVD and whether there is a dose-response relationship is still incompletely
      understood. METHODS: Thirty-two rats ages 8 weeks were divided into four groups
      with eight animals each. The first 8 weeks were the adaptive phase, the
      overtraining phase was from the ninth to the eleventh week, which consisted of
      increasing the number of daily training sessions from 1 to 4 and the recovery
      phase was represented by the 12th and 13th weeks without training. Control group
      1 (CG1) did not undergo any kind of training. Control group 2 (CG2) completed
      just the adaptive phase. Overtraining group 1 (OT1) completed the overtraining
      phase. Overtraining group 2 (OT2) completed the recovery phase. Running
      performance tests were used to assess the "overtraining" status of the animals.
      IVD glycosaminoglycans were extracted and quantified, and identified by
      electrophoresis. RESULTS: Glycosaminoglycans showed a distribution between
      chondroitin sulfate and dermatan sulfate. Glycosaminoglycans quantification
      showed decreasing concentration at the following order: OT1 > CG2 > OT2 > CG1.
      Increased expression of dermatan sulfate was verified at the groups submitted to
      any training. CONCLUSION: Overtraining condition, as assessed by muscle and
      cardiovascular endurance did not lessen glycosaminoglycan concentration in the
      IVD. In fact, physical exercise increased glycosaminoglycan concentration in the
      IVD in proportion to the training load, even at overtraining condition, returning
      to normal levels after the recovery phase and glycosaminoglycan production is a
      reversible acute positive response for mechanical stimulation of the IVD. LEVEL
      OF EVIDENCE: N/A.

PMID- 28767622
TI  - Adiponectin Downregulates TNF-alpha Expression in Degenerated Intervertebral
      Discs.
AB  - STUDY DESIGN: Given the results of previous in vitro investigations of the
      expression patterns of adiponectin and its receptors in healthy and degenerated
      intervertebral discs (IVDs), we studied the effects of adiponectin on tumor
      necrosis factor-alpha (TNF-alpha) production in degenerated nucleus pulposus (NP)
      cells and analyzed the association between adiponectin levels in IVD tissues and
      IVD Pfirrmann grades. OBJECTIVE: The aim of this study was to investigate the
      potential role of adiponectin in the pathogenesis of IVD degeneration. SUMMARY OF
      BACKGROUND DATA: Adiponectin has been reported to be involved in physiologic and
      pathologic processes associated with bone and cartilage diseases. However, the
      expression profiles of adiponectin and its receptors in human IVD tissues and the
      function of adiponectin in the pathogenesis of IVD degeneration remain unknown.
      METHODS: Real-time polymerase chain reaction, immunohistochemistry, and western
      blotting were performed to examine the expression levels of adiponectin,
      adiponectin receptors, and TNF-alpha in IVD tissues and isolated NP cells. The
      effects of adiponectin on TNF-alpha production in degenerated NP cells were
      detected by enzyme linked immunosorbent assay. RESULTS: Adiponectin expression
      levels were downregulated, while adiponectin receptor 1 (adipoR1) and adipoR2
      expression levels were upregulated in degenerated IVD tissues and degenerated NP
      cells compared with those in healthy IVD tissues and healthy NP cells. Moreover,
      we confirmed that TNF-alpha production by degenerated NP cells was downregulated
      by adiponectin administration in a dose- and time-dependent manner. Furthermore,
      our data showed that adiponectin levels in degenerated IVD tissues were inversely
      correlated with IVD Pfirrmann grades. CONCLUSION: These results indicated that
      adiponectin may play an anti-inflammatory role with respect to the maintenance of
      IVD homeostasis by downregulating TNF-alpha production. LEVEL OF EVIDENCE: N/A.

PMID- 28767623
TI  - Spinopelvic Changes Based on the Simplified SRS-Schwab Adult Spinal Deformity
      Classification: Relationships With Disability and Health-Related Quality of Life
      in Adult Patients With Prolonged Degenerative Spinal Disorders.
AB  - STUDY DESIGN: Cross-sectional, observational study. OBJECTIVE: To study the
      occurrence of sagittal malalignment, the adaptability of a simplified sagittal
      modifiers grading of the Scoliosis Research Society (SRS)-Schwab adult spinal
      deformity (ASD) classification, and the deformity-specific SRS questionnaire
      version 30 (SRS-30) in an unselected adult cohort with symptomatic degenerative
      spinal disorders. SUMMARY OF BACKGROUND DATA: The sagittal modifiers of the SRS
      Schwab ASD classification correlate with health-related quality of life (HRQoL)
      measures in patients with ASD. The deformities and disabilities caused by
      sagittal malalignment in patients with common degenerative spinal disorders of
      multiple etiologies are rarely studied. A simplified and categorizing version of
      the SRS-Schwab ASD classification in relation to the Oswestry Disability Index
      (ODI) and the SRS-30 outcomes has not yet been developed. METHODS: We recruited
      874 consecutive patients with degenerative spinal disorders between March 2013
      and February 2014. Full spine radiographs were taken and the patients divided
      into sagittal deformity severity groups: mild or none, moderate, and marked
      deformity. Participants completed the ODI, SRS-30, and a general health
      questionnaire. RESULTS: We included 637 patients in the analysis. The severity of
      sagittal deformity was mild or none in 407 (63.9%) patients, moderate in 159
      (25.0%), and marked in 71 (11.1%). Linearity across the modifier grades and
      deformity classes was found for ODI total score (P = 0.033), and the
      function/activity (P = 0.004) and self-image/appearance (P = 0.030) domains of
      the SRS-30. Age, body mass index, duration of symptoms, and the use of
      painkillers increased while physical activity, working, and educational status
      decreased significantly with deformity severity. CONCLUSION: Sagittal spinopelvic
      malalignment is significantly related to deterioration of the ODI and the SRS-30
      in symptomatic adults with degenerative spinal disorders. The SRS-Schwab
      classification sagittal modifiers categorized into three groups is a practical
      tool to detect various clinically significant grades of deformity in a cohort
      with no recognized ASD. LEVEL OF EVIDENCE: 3.

PMID- 28767621
TI  - The UTE Disc Sign on MRI: A Novel Imaging Biomarker Associated With Degenerative
      Spine Changes, Low Back Pain, and Disability.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVE: To assess the distribution of the ultra
      short time-to-echo (UTE) disc sign (UDS) and its association with disc
      degeneration, other magnetic resonance imaging (MRI) phenotypes, pain, and
      disability profiles. SUMMARY OF BACKGROUND DATA: Disc degeneration has been
      conventionally assessed by T2-weighted (T2W) signal intensity on MRI; however,
      its clinical utility has been questionable. UTE MRI assesses short T2 components.
      The authors have identified a new imaging biomarker on UTE-the UDS. METHODS: One
      hundred eight subjects were recruited. T2W MRI assessed disc degeneration and
      other phenotypes, and T1-rho MRI values represented quantitative proteoglycan
      disc profiles of L1-S1. UDS was detected on UTE (i.e., hyper-/hypointense disc
      band). A UDS score (cumulative number of UDS levels) and T2W summated lumbar
      degenerated scores (cumulative disc degeneration score) were assessed. Subject
      demographics, chronic low back pain (LBP), and disability profiles (Oswestry
      Disability Index: ODI) were obtained. RESULTS: UDS was noted in 39.8% subjects,
      61.4% occurred at the lower lumbar spine and 39.5% had multilevel UDS. UDS
      subjects had significantly greater severity and extent of disc degeneration, and
      Modic changes (P < 0.05). By disc levels, a higher prevalence of disc
      degeneration/displacement, Modic changes, and spondylolisthesis were noted in UDS
      discs than non-UDS discs (P < 0.05). T1-rho values were also lower in UDS discs
      (P = 0.022). The majority of UDS could not be detected on T2W. The UDS score
      significantly correlated with worse ODI scores (r = 0.311; P = 0.001), whereas
      T2W cumulative disc degeneration score did not (r = 0.13; P = 0.19). LBP subjects
      exhibited more multilevel UDS (P < 0.015) but not on T2W MRI (P = 0.53). The UDS
      score was significantly related to LBP (P = 0.009), whereas T2W cumulative disc
      degeneration score was not (P = 0.127). CONCLUSION: This is the first study to
      report "UDS" in humans. UDS is a novel imaging biomarker that is highly
      associated with degenerative spine changes, chronic LBP, and disability than
      conventional T2W MRI. LEVEL OF EVIDENCE: 2.

PMID- 28767624
TI  - Can C7 Slope Substitute the T1 slope?: An Analysis Using Cervical Radiographs and
      Kinematic MRIs.
AB  - STUDY DESIGN: Retrospective analysis of consecutive 45 radiographs and 120
      kinematic magnetic resonance images (kMRI) OBJECTIVE.: The aim was to assess the
      visibility of C7 and T1 endplates on radiographs, and to verify the correlation
      between C7 or T1 slope and cervical balance parameters using kMRI. SUMMARY OF
      BACKGROUND DATA: Because the T1 slope is not always visible due to the anatomical
      interference, several studies have used C7 slope instead of T1. However, it is
      still unclear whether the C7 endplate is more visible on radiographs than T1, and
      if C7 slope has similarity with T1 slope. METHODS: The endplate visibility was
      determined using weight-bearing radiography. Subsequently, using weight-bearing
      MR images, the C7 slope of upper and lower endplate, T1 slope, C1 inclination, C2
      slope, atlas-dens interval (ADI), C2-C7 lordotic angle, cervical sagittal
      vertical axis (cSVA), cervical tilt, cranial tilt, neck tilt, thoracic inlet
      angle (TIA) were measured, for the analysis of correlation between three types of
      slopes and cervical balance parameters. RESULTS: 82% of the upper C7, and 18% of
      T1 endplate were clearly visible. The upper C7 endplate was significantly
      visible, whereas T1 endplate was significantly invisible (residual analysis, P <
      0.01). Linear regression analysis showed correlation between the upper C7 slope
      and T1 slope (R = 0.818, P < 0.01) and, lower C7 slope and T1 slope (R = 0.840, P
      < 0.01). T1 slope significantly correlated with neck tilt, TIA, C2-C7 angle,
      cSVA, cervical and cranial tilt, but not with the C1 inclination, C2 slope, and
      ADI. Upper and lower C7 slopes showed the close resemblance with T1 slope in
      terms of correlation with those parameters. CONCLUSION: Both, upper and lower C7
      slope correlated strongly with T1 slope and showed similar relationship with
      cervical balance parameters as T1 slope. Therefore, C7 slope could potentially
      substitute T1 slope, especially upper C7 slope due to the good visibility. LEVEL
      OF EVIDENCE: 3.

PMID- 28767625
TI  - Patient-Reported Outcomes and Costs Associated With Revision Surgery for
      Degenerative Cervical Spine Diseases.
AB  - STUDY DESIGN: A retrospective review of a prospective database. OBJECTIVE: The
      aim of this study was to determine cost and outcomes of revision cervical spine
      surgery. SUMMARY OF BACKGROUND DATA: Revision rates for cervical spine surgery
      are steadily increasing. It is important to counsel patients on expected results
      following a revision procedure. However, outcomes and cost of these procedures
      are poorly defined in the literature. METHODS: Patients undergoing revision
      cervical spine surgery at a single institution were included between October 2010
      and January 2016 in a prospective registry database. Patients were divided into
      three cohorts depending on their etiology for revision, including recurrent
      disease, pseudoarthrosis, or adjacent segment disease. Patient-reported outcomes
      (PROs), including Neck Disability Index (NDI), EuroQol-5D (EQ-5D), modified
      Japanese Orthopaedic Association (mJOA) score, numeric rating scale-neck pain
      (NRS-NP), and numeric rating scale-arm pain (NRS-AP), were measured at baseline
      and 12 months following revision surgery. Mean costs at 12 months following
      revision surgery were also calculated. Satisfaction was determined by the NASS
      patient satisfaction index. Variables were compared using Student t test.
      RESULTS: A total of 115 patients underwent cervical revision surgery for
      recurrent disease (n = 21), pseudoarthrosis (n = 45), and adjacent segment
      disease (n = 49). There was significant improvement in all patient-reported
      outcomes at 12 months following surgery regardless of etiology (P < 0.0001).
      Total cost of revision surgery ranged between 21,294 +/- 8614 and 23,914 +/-
      15,396 depending on pathology. No significant differences were seen between costs
      among different revision groups (P = 0.53). Satisfaction was met in 75.5% to
      85.7% (P = 0.21) of patients depending on the etiology of the revision need.
      Complication rates were between 4% and 9%. CONCLUSION: This is one of the first
      studies to determine costs and outcome measures in the setting of cervical spine
      revision surgery. On the basis of our analysis, a majority of patients can expect
      to receive some benefit by 12 months and are satisfied with their procedure.
      LEVEL OF EVIDENCE: 4.

PMID- 28767626
TI  - A Detailed Comparative Analysis of Anterior Versus Posterior Approach to Lenke 5C
      Curves.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To prospectively compare
      radiographic, perioperative, and functional outcomes between anterior spinal
      instrumentation and fusion (ASIF) and posterior spinal instrumentation and fusion
      (PSIF) in Lenke 5C curves. SUMMARY OF BACKGROUND DATA: Historically, ASIF has
      been the treatment of choice for treatment of thoracolumbar adolescent idiopathic
      scoliosis. More recently, PSIF has gained popularity for its ease, versatility,
      and amount of correction achieved. Current literature lacks a prospective
      comparative analysis between these two approaches to better aid treating surgeons
      in decision making when treating Lenke 5C curves. METHODS: A prospective,
      longitudinal multicenter adolescent idiopathic scoliosis database was used to
      identify 161 consecutive patients with Lenke 5C curves treated by ASIF with a
      dual rod system, or PSIF with a pedicle screw-rod construct. Pre- and 2-year
      postoperative radiographic data, Scoliosis Research Society outcome scores, and
      perioperative comparisons were made between the two approaches. RESULTS: A total
      of 69 patients were treated with ASIF and 92 patients with PSIF. Curve extent,
      magnitude, stable, and end vertebrae distribution before surgery were similar
      between the two groups. At 2-year follow-up, there were no significant
      differences in percentage correction of the main curve (ASIF: 59.1%, PSIF:
      59.6%), C7 decompensation (ASIF: -0.6 +/- 1.2, PSIF: -0.3 +/- 1.4 cm), length of
      hospital stay (ASIF: 5.6 days, PSIF: 5.7 days), postoperative day conversion to
      oral pain medication (ASIF: 3.2 days, PSIF: 3.2 days), and SRS outcome scores (P
      = 0.560) between the two groups. The number of levels fused was significantly
      lower in ASIF group (ASIF: 4.7, PSIF: 6.3; P < 0.001), but PSIF resulted in
      significantly less disc angulation below lowest instrumented vertebrae (ASIF: 3.4
      degrees , PSIF: 1.7 degrees ; P = 0.011), greater lumbar lordosis (P < 0.001),
      and greater % correction of lumbar prominence (P = 0.017). CONCLUSION: The amount
      of correction achieved was similar between ASIF and PSIF. ASIF resulted in
      shorter fusions (average 1.6 levels) compared with PSIF. This was at the expense
      of increased disc angulation below the lowest instrumented vertebrae, less lumbar
      lordosis, and a lower % correction of the lumbar prominence than PSIF. LEVEL OF
      EVIDENCE: 2.

PMID- 28767627
TI  - Muscle-Preserving Selective Laminectomy Maintained the Compensatory Mechanism of
      Cervical Lordosis After Surgery.
AB  - STUDY DESIGN: A retrospective single-center study. OBJECTIVE: The aim of this
      study was to evaluate the compensatory mechanism of cervical lordosis (CL), the
      changes in cervical sagittal alignment, and range of motion (ROM) after muscle
      preserving selective laminectomy (SL). SUMMARY OF BACKGROUND DATA: CL increases
      as a compensatory mechanism for the adjustment of cervical sagittal balance or
      horizontal gaze. However, laminoplasty invades this mechanism and causes kyphosis
      in higher T1 (C7) slope patients. METHODS: SL is a posterior surgery selecting
      the decompression laminae without disturbing the extensor musculature and facet
      joints. The clinical features and radiological findings of 125 cervical
      compressive myelopathy patients who underwent C6 single-level SL, C5-C6 two
      consecutive levels SL, C4-C6 three consecutive levels SL, and C3-C6 four
      consecutive levels SL were enrolled. Cervical spine lateral radiography was
      performed before surgery and at the final follow-up. The patients were divided
      into two groups according to the preoperative C7 slope. Postoperative cervical
      alignment change was compared between the higher and lower C7 slope groups.
      Subsequently, pre- and postoperative cervical alignment and cervical ROM were
      analyzed according to the number of consecutive laminae surgically treated.
      RESULTS: Patients with higher C7 slope had greater lordotic cervical alignment
      and larger C2-C7 sagittal vertical axis (SVA) pre- and postoperatively. No
      kyphotic alignment change was observed, even in the higher C7 slope group. C6 SL
      and C5-C6 SL did not affect C2-C7 angle, and did not increase C2-C7 SVA after
      surgery. Although C4-C6 SL and C3-C6 SL demonstrated postoperative slight
      increase in C2-C7 SVA, C2-C7 angle never decreased after surgery. Cervical ROM
      slightly reduced in the C4-C6 SL and C3-C6 SL groups; however, no reduction of
      ROM was observed in the C6 SL and C5-C6 SL groups. CONCLUSION: SL preserved the
      inherent compensatory CL that had been observed preoperatively and maintained
      cervical sagittal balance after surgery. LEVEL OF EVIDENCE: 4.

PMID- 28767628
TI  - Methicillin-Resistant Staphylococcus aureus Nasal Swab and Suction Drain Tip
      Cultures in 4573 Spinal Surgeries: Efficacy in Management of Surgical Site
      Infections.
AB  - STUDY DESIGN: A retrospective single-center study. OBJECTIVE: To assess the
      diagnostic value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab
      and suction drain tip cultures. SUMMARY OF BACKGROUND DATA: The prognostic value
      of MRSA nasal swab and suction drain tip cultures has not been firmly established
      in spinal surgery. METHODS: This study retrospectively included 4573 consecutive
      patients who underwent spinal surgery between January 2008 and December 2014.
      Patients diagnosed with infectious disease were excluded. Prophylactic
      antibiotics were administered intraoperatively and postoperatively for 48 hours.
      MRSA nasal swab cultures were taken from all patients before surgery. Drains were
      removed when the volume of postoperative fluid drainage was less than 50 mL in
      the preceding 24 hours and cultures were made. Surgical site infection (SSI) was
      defined according to Centers for Disease Control and Prevention criteria.
      RESULTS: SSI was identified in 94 cases (2.1%) and bacteria were isolated in 87
      cases (92.6%). Positive MRSA nasal swab cultures were identified in 49 cases
      (1.1%). There was no significant difference in the SSI positivity rate between
      the MRSA nasal swab culture (+) and (-) groups. Positive drain tip cultures were
      found in 382 cases (8.4%), 28 of which developed SSI. There was a significant
      difference in the SSI positivity rate between the drain tip culture (+) and (-)
      groups. The sensitivity of drain tip culture was 29.8% and the specificity was
      92.1%. In 16 of the 28 patients in the SSI (+) group with positive drain
      cultures, the same bacteria were isolated from the surgical site, giving a
      bacteria matching rate of 57.1%. CONCLUSION: MRSA nasal swab and drain tip
      cultures were not useful for predicting SSI. However, drain tip culture had a
      high positivity rate in the SSI group and the coincidence rate for the causative
      pathogen was relatively high. LEVEL OF EVIDENCE: 4.

PMID- 28767630
TI  - Predictive Findings of the Presence of Stooping in Patients With Lumbar
      Degenerative Kyphosis by Upright Whole Spine Lateral Radiography.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to
      identify the relationships between radiological findings and the presence of
      stooping in lumbar degenerative kyphosis (LDK). SUMMARY OF BACKGROUND DATA: Many
      studies have addressed fixed sagittal imbalances and surgical treatments.
      However, information regarding the relationship between radiological findings and
      stooping in LDK is sparse. METHODS: The study included 73 patients with LDK and
      44 with normal lumbar lordosis. Of those with LDK, 63 patients exhibited stooping
      (group 1) and 10 did not (group 2). Of those with 44 normal lumbar lordosis, 13
      patients exhibited stooping (group 3) and 31 patients did not (group 4).
      Radiographic parameters such as sacral slope (SS), pelvic tilt (PT), pelvic
      incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), horizontal distance
      between C7 plumb line and the posterosuperior corner of the sacrum (C7PL),
      sacrofemoral distance (SFD), C7PL/SFD ratio (C7/SFD), spinosacral angle (SSA),
      spinopelvic angle (SPA), C2-C7 lordosis (CL), C2-C7 sagittal vertical axis (C2-C7
      SVA), T1 slope, and T1 slope minus C2-C7 lordosis (TS-CL) were analyzed. RESULTS:
      Significant differences were observed in TK, LL, C7PL, SFD, C7/SFD, PT, SS, SSA,
      SPA, C2-C7 SVA, and TS-CL between LDK and normal lumbar lordosis, but no
      significant intergroup difference was observed in PI, CL, or T1 slope. These
      results showed that groups 1 and 3 had higher C7PL, C7/SFD, PT, and CL values
      than groups 2 and 4. Logistic regression analysis revealed that C7/SFD and CL
      could significantly predict stooping in LDK. CONCLUSION: C7/SFD and CL predict
      the presence of stooping in LDK. Furthermore, patients with LDK with compensatory
      mechanisms to maintain sagittal balance have low C7PL values, that is, C7/SFD <
      0.5 and high PT and CL on upright whole spine lateral radiography. LEVEL OF
      EVIDENCE: 3.

PMID- 28767629
TI  - Modic Changes and Disc Degeneration of Nonfused Segments 27 to 45 Years After
      Harrington Instrumentation for Adolescent Idiopathic Scoliosis: Comparison to
      Healthy Controls.
AB  - STUDY DESIGN: A case-control study. OBJECTIVE: The aim of this study was to
      investigate the long-term prevalence of the Modic changes and disc degeneration
      in the nonfused segments of the surgically treated adolescent idiopathic
      scoliosis (AIS) patients and compare with age- and sex-matched healthy controls.
      SUMMARY OF BACKGROUND DATA: No studies have looked at the association between
      Modic changes and low back pain in patients who underwent AIS surgery many years
      ago. METHODS: Study subjects consisted of 194 patients with AIS who underwent
      spinal fusion with Harrington instrumentation between 1968 and 1987. Twenty-six
      patients (AIS group) underwent lumbar magnetic resonance imaging (MRI), whole
      spine X-ray, and patient-reported outcomes evaluations [Scoliosis Research
      Society-22 Patient Questionnaire (SRS-22), Oswestry Disability Index (ODI)]. The
      mean duration of follow-up observation was 36.1 years. The lowest fusion vertebra
      was used as follows: T12: 2 patients, L1: 4, L2: 11, L3: 6, L4: 2, L5: 1. Twenty
      nine healthy age- and sex-matched individuals were selected as a control (CTR)
      group. RESULTS: On the basis of MRI findings, a significantly higher percentage
      of subjects showed Modic changes in the AIS group (AIS group: 57.7%, CTR group:
      13.8%). There were no significant differences in the percentage of subjects with
      disc degeneration rated Pfirrmann grade 4 or higher (AIS group: 61.5%, CTR group:
      65.5%). SRS-22 scores for function and self-image were significantly lower in the
      AIS group. ODI was significantly worse in the AIS group. Modic changes in AIS
      group were found in the concave side of the curve in 61.9%. The magnitude of
      lumbar coronal curve was found to be a significant risk factor of Modic changes.
      CONCLUSION: Modic changes were observed in 57.7% of AIS patients 27 years or more
      after spinal fusion with Harrington instrumentation. The magnitude of lumbar
      coronal curve was found to be a significant risk factor of Modic changes. Modic
      change occurred at a higher frequency in AIS patients than CTR individuals, with
      lower function and worse ODI scores. LEVEL OF EVIDENCE: 4.

PMID- 28767631
TI  - Neuroprotective Effects of C-terminal Domain of Tetanus Toxin on Rat Brain
      Against Motorneuron Damages After Experimental Spinal Cord Injury.
AB  - STUDY DESIGN: Experimental animal study investigating the efficacy of C-terminal
      domain of tetanus toxin application as neuroprotective effects on rat brain in a
      model of spinal cord injury (SCI). OBJECTIVE: The aim of the present study was to
      investigate the possible role of C-terminal domain of tetanus toxin (Hc-TeTx) on
      cell death mechanisms including apoptosis and autophagy following SCI. SUMMARY OF
      BACKGROUND DATA: Traumatic SCI can lead to posttraumatic inflammation, oxidative
      stress, motor neuron apoptosis, necrosis, and autophagy of tissue. To promote and
      enhance recovery after SCI, recent development of devices and therapeutic
      interventions are needed. METHODS: Twenty-eight adult rats were divided into four
      groups (n = 7 each) as follows: sham, trauma (SCI), SCI + Hc-TeTx, and SCI +
      methylprednisolone groups. The functional neurological deficits due to the SCI
      were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB)
      open-field locomotor test. The alterations in pro-/anti-apoptotic and autophagy
      related-protein levels were measured by Western blotting technique. RESULTS: In
      this study, Hc-TeTx promotes locomotor recovery and motor neuron survival of SCI
      rats. Hc-TeTx also decreased expression of bax, bad, bak, cleaved caspase-3,
      Ask1, and autophagy-related proteins including Atg5 and LC3II in brain. Our study
      provides an evidence that cell death mechanisms play critical roles in SCI and
      that the nontoxic peptides including Hc-TeTx may exert protective effect and
      decrease cell death following SCI. CONCLUSION: Our preliminary findings suggest a
      possible therapeutic agent to improve survival after spinal cord trauma, but
      further analysis are still needed to evaluate the difference between acute and
      chronic injuries. LEVEL OF EVIDENCE: N/A.

PMID- 28767632
TI  - Rod Lengthening With the Magnetically Controlled Growing Rod: Factors Influencing
      Rod Slippage and Reduced Gains During Distractions.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To identify the factors that are
      associated with rod slippage and to study the pattern of achieved length gain
      with a standard distraction methodology. SUMMARY OF BACKGROUND DATA: Ability to
      achieve successful magnetically controlled growing rod (MCGR) distraction is
      crucial for gradual spine lengthening. Rod slippage has been described as a
      failure of internal magnet rotation leading to a slippage and an inability to
      distract the rod. However, its onset, significance, and risk factors are
      currently unknown. In addition, how this phenomenon pertains to actual distracted
      lengths is also unknown. METHODS: A total of 22 patients with MCGR and at least
      six distraction episodes were prospectively studied. Patients with rod slippage
      occurring less than six distraction episodes were considered early rod slippage
      whereas those with more than six episodes or have yet to slip were grouped as
      late rod slippage. The association of parameters including body habitus, maturity
      status, age of implantation, total number of distractions, months of distraction
      from initial implantation, initial and postoperative Cobb angle, T1-T12, T1-S1,
      T5-T12 kyphosis, curve flexibility, instrumented length, and distance between
      magnets in dual rods and between the magnets and apex of the curve with early or
      late onset of rod slippage were studied. Differences between expected and
      achieved distraction lengths were assessed with reference to rod slippage
      episodes and rod exchanges to determine any patterns of diminishing returns.
      RESULTS: Patients had mean age of 7.1 years at diagnosis with mean follow-up of
      49.8 months. A mean 32.4 distractions were performed per patient. Early rod
      slippage occurred in 14 patients and late rod slippage occurred in eight
      patients. Increased height, weight, body mass index, older age, increased T1-12
      and T1-S1 lengths, and less distance between magnets were significantly
      associated with early rod slippage. Expected distraction lengths did not
      translate to achieve distraction lengths and reduced gains were only observed
      after achieving one-third of the allowable distracted length in the MCGR. Length
      gains return to baseline after rod exchange. CONCLUSION: This is the first study
      to specifically analyze the impact of rod slippage on distraction lengths and the
      risk factors associated with its onset and frequency. Increased body habitus and
      reduced distance between internal magnets significantly influenced rod slippage
      events. Diminishing returns in distracted length gains were only observed after a
      period of usage. LEVEL OF EVIDENCE: 3.

PMID- 28767633
TI  - TO THE EDITOR.

PMID- 28767634
TI  - TO THE EDITOR.

PMID- 28767635
TI  - TO THE EDITOR.

PMID- 28767636
TI  - Comparison of Symptoms From C6 and C7 Radiculopathy.
AB  - STUDY DESIGN: Case series. OBJECTIVE: This study compared the locations of arm
      pain, sensory symptoms, and subjective complaints of arm weakness in patients
      with cervical radiculopathy from MRI confirmed C6 and C7 nerve root compression.
      SUMMARY OF BACKGROUND DATA: Cervical radiculopathy is defined as arm pain,
      sensory and motor symptoms caused by irritation of a cervical nerve root. The C6
      and C7 roots are most commonly involved, and differentiating symptoms associated
      with each root has proven difficult. Cervical MRI allows accurate identification
      of nerve root compression and therefore makes it possible to explore symptom
      patterns that may differentiate C6 from C7 radiculopathy. METHODS: A total of 122
      patients with symptoms suggestive of cervical radiculopathy were recruited. Of
      these, 30 patients had MRI confirmed C6 and 39 patients C7 nerve root
      compression. By completing a study questionnaire, patients reported specific arm
      weakness, and marked the location of arm pain and tingling/numbness on graphic
      representations of the arm. Marked areas were interpreted by superimposing a grid
      that divided the arm into 54 distinct areas. The frequencies of reported symptoms
      with C6 and C7 were totaled and then compared with likelihood rations. Power
      analysis calculated that 27 patients would be needed in each group based on the
      assumption that a 30 percentage point difference in frequency of specific symptom
      would be clinically useful for differentiating C6 from C7 radiculopathy. RESULTS:
      Arm pain and sensory symptoms were diffuse, and were not distinctly different for
      C6 or C7 radiculopathy. Some weakness was reported by 41 percent of patients,
      with specific descriptions of weakness having limited value for differentiating
      between radiculopathies. CONCLUSION: The location of pain and sensory symptoms,
      and specific weakness complaints associated with symptomatic C6 and C7 nerve root
      compression overlap to the extent that caution should be exercised when
      predicting root involvement based on symptoms. LEVEL OF EVIDENCE: 3.

PMID- 28767637
TI  - Osmotic Pressure Alters Time-dependent Recovery Behavior of the Intervertebral
      Disc.
AB  - STUDY DESIGN: Disc recovery behavior under hypo- and hyperosmotic pressure.
      OBJECTIVE: To evaluate the effect of osmotic pressure on the unloaded recovery
      response of healthy discs. SUMMARY OF BACKGROUND DATA: The intervertebral disc is
      a poroviscoelastic material that experiences large fluctuations in water
      composition throughout a diurnal loading cycle. Fluid flow out of the disc occurs
      through mechanical loading, whereas fluid flow into the disc occurs through
      passive diffusion because of an imbalance of ions between the disc and its
      surrounding environment. Osmotic pressure has been used to alter water uptake and
      tissue hydration. METHODS: Motion segments were prepared from the caudal spine
      sections of the skeletally mature bovines. A 300-N compressive load was applied
      for 2 hours before unloaded recovery for 12 hours. Hypo- and hyperosmotic
      pressure was used to alter the rate of water uptake and disc height recovery
      during unloaded recovery. A 5-parameter rheological model was used to describe
      the disc's time-dependent recovery behavior. RESULTS: The elastic response was
      not altered by changes in osmotic pressure; however, viscoelastic recovery was
      highly dependent on saline osmolarity and recovery time. The fast response of
      viscoelastic recovery was not dependent on osmotic pressure. The time constant
      for the slow response decreased whereas the slow response stiffness increased as
      osmotic pressure increased. CONCLUSION: The fast response of viscoelastic
      recovery is governed by flow-independent recovery, whereas the slow response is
      related to flow-dependent recovery. The rate and magnitude of flow-dependent
      recovery are highly sensitive to changes in osmotic pressure of the saline bath.
      There is an osmotic pressure that reduces disc recovery behavior to an elastic
      response or flow-independent recovery. LEVEL OF EVIDENCE: N/A.

PMID- 28767638
TI  - Low Bone-Mineral Density Is a Significant Risk for Proximal Junctional Failure
      After Surgical Correction of Adult Spinal Deformity: A Propensity Score-Matched
      Analysis.
AB  - STUDY DESIGN: A propensity-matched comparison of risk factors for proximal
      junctional failure (PJF), which is a symptomatic proximal junctional kyphosis
      developing after corrective surgery for adult spinal deformity (ASD). OBJECTIVE:
      To elucidate the role of bone strength for developing PJF. SUMMARY OF BACKGROUND
      DATA: PJF, a devastating complication of corrective surgery for ASD, often recurs
      even after revision surgery. Most studies of risk factors for PJF are
      retrospective and have a selection bias in surgical strategy, making it difficult
      to identify modifiable PJF risk factors. METHODS: We conducted propensity-matched
      comparisons of 113 surgically treated ASD patients who were followed for at least
      2 years, to elucidate whether low bone-mineral density (BMD) was a true risk
      factor for PJF in a uniform population from a multicenter database. Patients were
      grouped as having mildly low to normal BMD (M group; T-score? - 1.5) or
      significantly low BMD (S group; T-score <  -1.5), and were propensity-matched for
      age, upper and lower instrumented vertebrae, history of spine surgery, and Schwab
      Scoliosis Research Society (SRS) ASD classification. PJF was defined as a >=20
      degrees  increase from the baseline proximal junction angle with a concomitant
      deterioration of at least one SRS-Schwab sagittal modifier grade, or any type of
      proximal junctional kyphosis requiring revision. RESULTS: PJF developed in 22 of
      113 patients (19%). There were 48 propensity-matched patients in the M and S
      groups (24 in each) with similar parameters for age, body mass index, number of
      vertebrae involved, C7SVA, pelvic incidence  - LL, and SRS-Schwab type. In this
      propensity-matched population, the incidence of PJF was significantly higher in
      the S group (33% vs. 8%, P < 0.01, odds ratio 6.4, 95% CI: 1.2-32.3). CONCLUSION:
      Low BMD was a significant risk factor for PJF in this propensity-matched cohort
      (odds ratio 6.4). Surgeons should consider prophylactic treatments when
      correcting ASD in patients with low BMD. LEVEL OF EVIDENCE: 3.

PMID- 28767639
TI  - Inaccuracies in ICD Coding for Obesity Would Be Expected to Bias Administrative
      Database Spine Studies Toward Overestimating the Impact of Obesity on
      Perioperative Adverse Outcomes.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine if
      International Classification of Diseases (ICD) coding for obesity is biased
      toward certain subgroups and how potential bias may influence the outcomes of
      database research in spine. SUMMARY OF BACKGROUND DATA: There has been increased
      use of national databases using administrative data in the spine surgery
      literature. Past research demonstrates that sensitivity of ICD codes for obesity
      is poor, but it is unknown if such inaccuracies are systematically biased and if
      they may bias studies utilizing such data. METHODS: Patients who underwent
      elective posterior lumbar fusion, 2013 to 2016, at a large academic hospital were
      identified. All ICD codes assigned to the encounter were obtained. Body mass
      index (BMI) was calculated based on height and weight. The sensitivity of ICD
      coding for obesity was calculated. Sensitivity was compared for subgroups defined
      by demographic, comorbidity, intraoperative, and postoperative factors. The
      association of obesity (as defined by BMI>=30 and ICD coding) with 30-day
      postoperative adverse events was tested with multivariate regression. RESULTS:
      The study included 796 patients. The overall sensitivity of ICD coding for
      obesity was 42.5%. The sensitivity of ICD coding for obesity was significantly
      higher in patients with greater BMI, diabetes, American Society of
      Anesthesiologists class>=III, increased length of stay, venous thromboembolism,
      any adverse event, and major adverse event. Multivariate analysis for determining
      outcomes of increased risk with obesity as defined by ICD coding included venous
      thromboembolism, major adverse events, and any adverse events. However,
      multivariate analysis for determining outcomes of increased risk with obesity
      defined by BMI did not yield any positive associations. CONCLUSION: ICD codes for
      obesity are more commonly assigned to patients with other comorbidities or
      postoperative complications. Further, use of such nonrandomly assigned ICD codes
      for obesity has the potential to skew studies to suggest greater associated
      adverse events than calculated BMI would demonstrate. LEVEL OF EVIDENCE: 3.

PMID- 28767640
TI  - Efficacy and Safety of 3 Different Anesthesia Techniques Used in Total Hip
      Arthroplasty.
AB  - BACKGROUND This study compared the efficacy and safety of 3 different anesthesia
      techniques used in total hip arthroplasty (THA). MATERIAL AND METHODS We
      allocated 198 patients preparing to undertake THA into 3 groups: general
      anesthesia group (GA group, n=66), caudal epidural anesthesia group (CEA group,
      n=66), and spinal-epidural anesthesia group (SEA group, n=66). We compared
      postoperative adverse effects occurring in patients of the 3 anesthesia groups.
      The Visual Analog Scale (VAS) score, Minimum Mental State Examination (MMSE)
      score, and beta-amyloid (Abeta) expression were calculated to determine the
      effects of different anesthesia on the postoperative pain and cognitive
      dysfunction of patients. RESULTS The CEA and SEA groups had lower rates of
      perioperative adverse effects than in the GA group. Patients in the GA group
      required significantly higher administration of analgesics after the surgery than
      those in CEA and SEA groups. Higher Abeta expression levels and VAS scores, as
      well as lower MMSE scores, were also seen in the GA group compared with the other
      2 groups. CONCLUSIONS CEA and SEA were more effective than GA in THA, and CEA
      seemed to be a better anesthesia technique than SEA.

PMID- 28767642
TI  - Time for the data to speak.

PMID- 28767641
TI  - ISWI chromatin remodellers sense nucleosome modifications to determine substrate
      preference.
AB  - ATP-dependent chromatin remodellers regulate access to genetic information by
      controlling nucleosome positions in vivo. However, the mechanism by which
      remodellers discriminate between different nucleosome substrates is poorly
      understood. Many chromatin remodelling proteins possess conserved protein domains
      that interact with nucleosomal features. Here we used a quantitative high
      throughput approach, based on the use of a DNA-barcoded mononucleosome library,
      to profile the biochemical activity of human ISWI family remodellers in response
      to a diverse set of nucleosome modifications. We show that accessory (non-ATPase)
      subunits of ISWI remodellers can distinguish between differentially modified
      nucleosomes, directing remodelling activity towards specific nucleosome
      substrates according to their modification state. Unexpectedly, we show that the
      nucleosome acidic patch is necessary for maximum activity of all ISWI remodellers
      evaluated. This dependence also extends to CHD and SWI/SNF family remodellers,
      suggesting that the acidic patch may be generally required for chromatin
      remodelling. Critically, remodelling activity can be regulated by modifications
      neighbouring the acidic patch, signifying that it may act as a tunable
      interaction hotspot for ATP-dependent chromatin remodellers and, by extension,
      many other chromatin effectors that engage this region of the nucleosome surface.

PMID- 28767643
TI  - Bow-tie signaling in c-di-GMP: Machine learning in a simple biochemical network.
AB  - Bacteria of many species rely on a simple molecule, the intracellular secondary
      messenger c-di-GMP (Bis-(3'-5')-cyclic dimeric guanosine monophosphate), to make
      a vital choice: whether to stay in one place and form a biofilm, or to leave it
      in search of better conditions. The c-di-GMP network has a bow-tie shaped
      architecture that integrates many signals from the outside world-the input
      stimuli-into intracellular c-di-GMP levels that then regulate genes for biofilm
      formation or for swarming motility-the output phenotypes. How does the
      'uninformed' process of evolution produce a network with the right input/output
      association and enable bacteria to make the right choice? Inspired by new data
      from 28 clinical isolates of Pseudomonas aeruginosa and strains evolved in
      laboratory experiments we propose a mathematical model where the c-di-GMP network
      is analogous to a machine learning classifier. The analogy immediately suggests a
      mechanism for learning through evolution: adaptation though incremental changes
      in c-di-GMP network proteins acquires knowledge from past experiences and enables
      bacteria to use it to direct future behaviors. Our model clarifies the elusive
      function of the ubiquitous c-di-GMP network, a key regulator of bacterial social
      traits associated with virulence. More broadly, the link between evolution and
      machine learning can help explain how natural selection across fluctuating
      environments produces networks that enable living organisms to make sophisticated
      decisions.

PMID- 28767644
TI  - Cryptic diversity in Ptyodactylus (Reptilia: Gekkonidae) from the northern Hajar
      Mountains of Oman and the United Arab Emirates uncovered by an integrative
      taxonomic approach.
AB  - The Hajar Mountains of south-eastern Arabia form an isolated massif surrounded by
      the sea to the east and by a large desert to the west. As a result of their old
      geological origin, geographical isolation, complex topography and local climate,
      these mountains provide an important refuge for endemic and relict species of
      plants and animals. With 19 species restricted to the Hajar Mountains, reptiles
      are the vertebrate group with the highest level of endemicity, becoming an
      excellent model for understanding the patterns and processes that generate and
      shape diversity in this arid mountain range. The geckos of the Ptyodactylus
      hasselquistii species complex are the largest geckos in Arabia and are found
      widely distributed across the Arabian Mountains, constituting a very important
      component of the reptile mountain fauna. Preliminary analyses suggested that
      their diversity in the Hajar Mountains may be higher than expected and that their
      systematics should be revised. In order to tackle these questions, we inferred a
      nearly complete calibrated phylogeny of the genus Ptyodactylus to identify the
      origin of the Hajar Mountains lineages using information from two mitochondrial
      and four nuclear genes. Genetic variability within the Hajar Mountains was
      further investigated using 68 specimens of Ptyodactylus from 46 localities
      distributed across the entire mountain range and sequenced for the same genes as
      above. The molecular phylogenies and morphological analyses as well as niche
      comparisons indicate the presence of two very old sister cryptic species living
      in allopatry: one restricted to the extreme northern Hajar Mountains and
      described as a new species herein; the other distributed across the rest of the
      Hajar Mountains that can be confidently assigned to the species P. orlovi.
      Similar to recent findings in the geckos of the genus Asaccus, the results of the
      present study uncover more hidden diversity in the northern Hajar Mountains and
      stress once again the importance of this unique mountain range as a hot spot of
      biodiversity and a priority focal point for reptile conservation in Arabia.

PMID- 28767645
TI  - The origin of the Acheulean. Techno-functional study of the FLK W lithic record
      (Olduvai, Tanzania).
AB  - The Acheulean materials documented in FLK West dated c. 1.7 Ma. are the focus of
      the present work. An original techno-functional approach is applied here to
      analyze the origin of Acheulean tools. According to the results, these tools were
      employed in different functional contexts in which tasks of different durations
      that transformed resources with different resistances were carried out. The
      exploitation of large and resistant resources suggests that the economic
      mechanism governing the manufacture of these tools was an increase in the demand
      of the work load. The decision processes underlying the production of these tools
      have thus an evident functional motivation. However, the presence of a refined
      handaxe in the studied sample indicates that the design form and production
      principles of handaxe manufacture were the result of an abrupt emergence rather
      than a long gradual development. The integration of mechanical and ergonomic
      investigation in our research has been crucial to explain how a core-and-flake
      industry gave way to a technology based on the production of large and heavy
      shaped tools.

PMID- 28767646
TI  - A model of human motor sequence learning explains facilitation and interference
      effects based on spike-timing dependent plasticity.
AB  - The ability to learn sequential behaviors is a fundamental property of our
      brains. Yet a long stream of studies including recent experiments investigating
      motor sequence learning in adult human subjects have produced a number of
      puzzling and seemingly contradictory results. In particular, when subjects have
      to learn multiple action sequences, learning is sometimes impaired by proactive
      and retroactive interference effects. In other situations, however, learning is
      accelerated as reflected in facilitation and transfer effects. At present it is
      unclear what the underlying neural mechanism are that give rise to these diverse
      findings. Here we show that a recently developed recurrent neural network model
      readily reproduces this diverse set of findings. The self-organizing recurrent
      neural network (SORN) model is a network of recurrently connected threshold units
      that combines a simplified form of spike-timing dependent plasticity (STDP) with
      homeostatic plasticity mechanisms ensuring network stability, namely intrinsic
      plasticity (IP) and synaptic normalization (SN). When trained on sequence
      learning tasks modeled after recent experiments we find that it reproduces the
      full range of interference, facilitation, and transfer effects. We show how these
      effects are rooted in the network's changing internal representation of the
      different sequences across learning and how they depend on an interaction of
      training schedule and task similarity. Furthermore, since learning in the model
      is based on fundamental neuronal plasticity mechanisms, the model reveals how
      these plasticity mechanisms are ultimately responsible for the network's sequence
      learning abilities. In particular, we find that all three plasticity mechanisms
      are essential for the network to learn effective internal models of the different
      training sequences. This ability to form effective internal models is also the
      basis for the observed interference and facilitation effects. This suggests that
      STDP, IP, and SN may be the driving forces behind our ability to learn complex
      action sequences.

PMID- 28767647
TI  - Differential spontaneous recovery across cognitive abilities during
      detoxification period in alcohol-dependence.
AB  - OBJECTIVE: There is a lack of consensus regarding the extent to which cognitive
      dysfunctions may recover upon cessation of alcohol intake by alcohol-dependents
      (AD), and the divergent findings are most likely due to methodological
      differences between the various studies. The present study was aimed at
      conducting a very strict longitudinal study of cognitive recovery in terms of
      assessment points, the duration of abstinence, control of age and duration of the
      addiction, and by use of individual analyses in addition to mean group
      comparisons. Our study further focused on the 2-3 week phase of alcohol
      detoxification that is already known to positively affect many biological,
      emotional, motivational, as well as neural variables, followed by longer-term
      therapies for which good cognitive functioning is needed. METHODS: 41 AD
      inpatients undergoing a detoxification program, and 41 matched controls, were
      evaluated twice in terms of five cognitive functions (i.e., short-term memory,
      working memory, inhibition, cognitive flexibility, and verbal fluency) within a
      three-week interval [on the first day (T1) and the 18th day (T2) of abstinence
      for AD patients]. Emotional (positive and negative affectivity and depression)
      and motivational (craving) variables were also measured at both evaluation times.
      RESULTS: Although verbal fluency, short-term memory, and cognitive flexibility
      did not appear to be affected, the patients exhibited impaired inhibition and
      working memory at T1. While no recovery of inhibition was found to occur, the
      average working memory performance of the patients was comparable to that of the
      controls at T2. Improvements in emotional and motivational dimensions were also
      observed, although they did not correlate with the ones in working memory.
      Individual analysis showed that not all participants were impaired or recover the
      same functions. CONCLUSIONS: While inhibition deficits appear to persist after 18
      days of detoxification, deficits in working memory, which is a central component
      of cognition, are greatly reduced after alcohol detoxification. Individual
      differences in the trajectory of recovery do arise however, and it might be worth
      implementing individual assessments of impaired functions at the end of the
      detoxification phase in order to maximize the chances of success in longer-term
      treatments and abstinence.

PMID- 28767648
TI  - Across the Indian Ocean: A remarkable example of trans-oceanic dispersal in an
      austral mygalomorph spider.
AB  - The Migidae are a family of austral trapdoor spiders known to show a highly
      restricted and disjunct distribution pattern. Here, we aim to investigate the
      phylogeny and historical biogeography of the group, which was previously thought
      to be vicariant in origin, and examine the biogeographic origins of the genus
      Moggridgea using a dated multi-gene phylogeny. Moggridgea specimens were sampled
      from southern Australia and Africa, and Bertmainus was sampled from Western
      Australia. Sanger sequencing methods were used to generate a robust six marker
      molecular dataset consisting of the nuclear genes 18S rRNA, 28S rRNA, ITS rRNA,
      XPNPEP3 and H3 and the mitochondrial gene COI. Bayesian and Maximum Likelihood
      methods were used to analyse the dataset, and the key dispersal nodes were dated
      using BEAST. Based on our data, we demonstrate that Moggridgea rainbowi from
      Kangaroo Island, Australia is a valid member of the otherwise African genus
      Moggridgea. Molecular clock dating analyses show that the inter-specific
      divergence of M. rainbowi from African congeners is between 2.27-16.02 million
      years ago (Mya). This divergence date significantly post-dates the separation of
      Africa from Gondwana (95 Mya) and therefore does not support a vicariant origin
      for Australian Moggridgea. It also pre-dates human colonisation of Kangaroo
      Island, a result which is further supported by the intra-specific divergence date
      of 1.10-6.39 Mya between separate populations on Kangaroo Island. These analyses
      provide strong support for the hypothesis that Moggridgea colonised Australia via
      long-distance trans-Indian Ocean dispersal, representing the first such
      documented case in a mygalomorph spider.

PMID- 28767649
TI  - Oiling accelerates loss of salt marshes, southeastern Louisiana.
AB  - The 2010 BP Deepwater Horizon (DWH) oil spill damaged thousands of km2 of
      intertidal marsh along shorelines that had been experiencing elevated rates of
      erosion for decades. Yet, the contribution of marsh oiling to landscape-scale
      degradation and subsequent land loss has been difficult to quantify. Here, we
      applied advanced remote sensing techniques to map changes in marsh land cover and
      open water before and after oiling. We segmented the marsh shorelines into non
      oiled and oiled reaches and calculated the land loss rates for each 10% increase
      in oil cover (e.g. 0% to >70%), to determine if land loss rates for each reach
      oiling category were significantly different before and after oiling. Finally, we
      calculated background land-loss rates to separate natural and oil-related erosion
      and land loss. Oiling caused significant increases in land losses, particularly
      along reaches of heavy oiling (>20% oil cover). For reaches with >=20% oiling,
      land loss rates increased abruptly during the 2010-2013 period, and the loss
      rates during this period are significantly different from both the pre-oiling (p
      < 0.0001) and 2013-2016 post-oiling periods (p < 0.0001). The pre-oiling and 2013
      2016 post-oiling periods exhibit no significant differences in land loss rates
      across oiled and non-oiled reaches (p = 0.557). We conclude that oiling increased
      land loss by more than 50%, but that land loss rates returned to background
      levels within 3-6 years after oiling, suggesting that oiling results in a large
      but temporary increase in land loss rates along the shoreline.

PMID- 28767650
TI  - The Stochastic Early Reaction, Inhibition, and late Action (SERIA) model for
      antisaccades.
AB  - The antisaccade task is a classic paradigm used to study the voluntary control of
      eye movements. It requires participants to suppress a reactive eye movement to a
      visual target and to concurrently initiate a saccade in the opposite direction.
      Although several models have been proposed to explain error rates and reaction
      times in this task, no formal model comparison has yet been performed. Here, we
      describe a Bayesian modeling approach to the antisaccade task that allows us to
      formally compare different models on the basis of their evidence. First, we
      provide a formal likelihood function of actions (pro- and antisaccades) and
      reaction times based on previously published models. Second, we introduce the
      Stochastic Early Reaction, Inhibition, and late Action model (SERIA), a novel
      model postulating two different mechanisms that interact in the antisaccade task:
      an early GO/NO-GO race decision process and a late GO/GO decision process. Third,
      we apply these models to a data set from an experiment with three mixed blocks of
      pro- and antisaccade trials. Bayesian model comparison demonstrates that the
      SERIA model explains the data better than competing models that do not
      incorporate a late decision process. Moreover, we show that the early decision
      process postulated by the SERIA model is, to a large extent, insensitive to the
      cue presented in a single trial. Finally, we use parameter estimates to
      demonstrate that changes in reaction time and error rate due to the probability
      of a trial type (pro- or antisaccade) are best explained by faster or slower
      inhibition and the probability of generating late voluntary prosaccades.

PMID- 28767651
TI  - An automated system for the objective evaluation of human gustatory sensitivity
      using tongue biopotential recordings.
AB  - The goal of this work is to develop an automatic system for the evaluation of the
      gustatory sensitivity of patients using an electrophysiological recording of the
      response of bud cells to taste stimuli. In particular, the study aims to evaluate
      the effectiveness and limitations of supervised classifiers in the discrimination
      between subjects belonging to the three 6-n-propylthiouracil (PROP) taster
      categories (supertasters, medium tasters, and non-tasters), exploiting features
      extracted from electrophysiological recordings of the tongue. Thirty-nine
      subjects (equally divided into the three PROP status classes by standard non
      objective scaling methods) underwent a non-invasive, differential, biopotential
      recording of their tongues during stimulation with PROP by using a custom-made,
      flexible, silver electrode. Two different classifiers were trained to recognize
      up to seven different features extracted from the recorded depolarization signal.
      The classification results indicate that the identified set of features allows to
      distinguish between PROP tasters and non-tasters (average accuracy of 80% +/- 18%
      and up to 94% +/- 15% when only supertasters and non-tasters are considered), but
      medium tasters were difficult to identify. However, these apparent classification
      errors are related to uncertainty in the labeling procedures, which are based on
      non-objective tests, in which the subjects provided borderline evaluations. Thus,
      using the proposed method, it is possible, for the first time, to automatically
      achieve objective PROP taster status identification with high accuracy. The
      simplicity of the recording technique allows for easy reproduction of the
      experimental setting; thus the technique can be used in future studies to
      evaluate other gustatory stimuli. The proposed approach represents the first
      objective and automatic method to directly measure human gustatory responses and
      a milestone for physiological taste studies, with applications ranging from basic
      science to food tasting evaluations.

PMID- 28767652
TI  - Comparative studies of three cholesteryl ester transfer proteins and their
      interactions with known inhibitors.
AB  - Cholesteryl ester transfer protein (CETP) is a plasma protein that mediates
      bidirectional transfers of cholesteryl esters and triglycerides between low
      density lipoproteins and high-density lipoproteins (HDL). Because low levels of
      plasma CETP are associated with increased plasma HDL-cholesterol, therapeutic
      inhibition of CETP activity is considered an attractive strategy for elevating
      plasma HDL-cholesterol, thereby hoping to reduce the risk of cardiovascular
      disease. Interestingly, only a few laboratory animals, such as rabbits, guinea
      pigs, and hamsters, have plasma CETP activity, whereas mice and rats do not. It
      is not known whether all CETPs in these laboratory animals are functionally
      similar to human CETP. In the current study, we compared plasma CETP activity and
      characterized the plasma lipoprotein profiles of these animals. Furthermore, we
      studied the three CETP molecular structures, physicochemical characteristics, and
      binding properties with known CETP inhibitors in silico. Our results showed that
      rabbits exhibited higher CETP activity than guinea pigs and hamsters, while these
      animals had different lipoprotein profiles. CETP inhibitors can inhibit rabbit
      and hamster CETP activity in a similar manner to human CETP. Analysis of CETP
      molecules in silico revealed that rabbit and hamster CETP showed many features
      that are similar to human CETP. These results provide novel insights into
      understanding CETP functions and molecular properties.

PMID- 28767653
TI  - In silico analysis to identify vaccine candidates common to multiple serotypes of
      Shigella and evaluation of their immunogenicity.
AB  - Shigellosis or bacillary dysentery is an important cause of diarrhea, with the
      majority of the cases occurring in developing countries. Considering the high
      disease burden, increasing antibiotic resistance, serotype-specific immunity and
      the post-infectious sequelae associated with shigellosis, there is a pressing
      need of an effective vaccine against multiple serotypes of the pathogen. In the
      present study, we used bio-informatics approach to identify antigens shared among
      multiple serotypes of Shigella spp. This approach led to the identification of
      many immunogenic peptides. The five most promising peptides based on MHC binding
      efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein
      (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL
      PGI V). These peptides were synthesized and the immunogenicity was evaluated in
      BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP)
      and the hypothetical protein elicited good humoral response, whereas putative
      lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by
      increased IFN-gamma and TNF-alpha cytokine levels. The patient sera from
      confirmed cases of shigellosis were also evaluated for the presence of peptide
      specific antibodies with significant IgG and IgA antibodies against the HSP and
      the hypothetical protein, bestowing them as potential future vaccine candidates.
      The antigens reported in this study are novel and have not been tested as vaccine
      candidates against Shigella. This study offers time and cost-effective way of
      identifying unprecedented immunogenic antigens to be used as potential vaccine
      candidates. Moreover, this approach should easily be extendable to find new
      potential vaccine candidates for other pathogenic bacteria.

PMID- 28767654
TI  - Cancer stem cell-related gene expression as a potential biomarker of response for
      first-in-class imipridone ONC201 in solid tumors.
AB  - Cancer stem cells (CSCs) correlate with recurrence, metastasis and poor survival
      in clinical studies. Encouraging results from clinical trials of CSC inhibitors
      have further validated CSCs as therapeutic targets. ONC201 is a first-in-class
      small molecule imipridone in Phase I/II clinical trials for advanced cancer. We
      have previously shown that ONC201 targets self-renewing, chemotherapy-resistant
      colorectal CSCs via Akt/ERK inhibition and DR5/TRAIL induction. In this study, we
      demonstrate that the anti-CSC effects of ONC201 involve early changes in stem
      cell-related gene expression prior to tumor cell death induction. A targeted
      network analysis of gene expression profiles in colorectal cancer cells revealed
      that ONC201 downregulates stem cell pathways such as Wnt signaling and modulates
      genes (ID1, ID2, ID3 and ALDH7A1) known to regulate self-renewal in colorectal,
      prostate cancer and glioblastoma. ONC201-mediated changes in CSC-related gene
      expression were validated at the RNA and protein level for each tumor type.
      Accordingly, we observed inhibition of self-renewal and CSC markers in prostate
      cancer cell lines and patient-derived glioblastoma cells upon ONC201 treatment.
      Interestingly, ONC201-mediated CSC depletion does not occur in colorectal cancer
      cells with acquired resistance to ONC201. Finally, we observed that basal
      expression of CSC-related genes (ID1, CD44, HES7 and TCF3) significantly
      correlate with ONC201 efficacy in >1000 cancer cell lines and combining the
      expression of multiple genes leads to a stronger overall prediction. These proof
      of-concept studies provide a rationale for testing CSC expression at the RNA and
      protein level as a predictive and pharmacodynamic biomarker of ONC201 response in
      ongoing clinical studies.

PMID- 28767655
TI  - Beluga whale summer habitat associations in the Nelson River estuary, western
      Hudson Bay, Canada.
AB  - To understand beluga whale (Delphinapterus leucas) estuarine use in the Nelson
      River estuary, southwest Hudson Bay, we recorded and examined beluga movements
      and habitat associations for the July through August period in 2002-2005. We
      compared locations of belugas fitted with satellite transmitters ("tags") (2002
      2005) and aerial-surveyed (2003 and 2005) belugas for years of differing
      freshwater flow from the Nelson River which is influenced by hydroelectric
      activity. Using the beluga telemetry location data, we estimated an early August
      behavioral shift in beluga distribution patterns from local estuarine use to a
      progressively more migratory behavior away from the estuary. The timing of this
      shift in behavior was also apparent in results of beluga aerial surveys from the
      1940s-1960s, despite environmental changes including later freeze-up and warming
      ocean temperatures. Overall, during the higher than average discharge ("wet")
      year of 2005, the three tagged belugas ranged farther from the Nelson River but
      not farther from the nearest shore along southwestern Hudson Bay, compared to the
      10 tagged belugas tracked during the "dry" years of 2002-2004 with below average
      discharges. Aerial survey data for 2003 and 2005 display a similar dry vs. wet
      year shift in spatial patterns, with no significant change in overall density of
      belugas within the study area. In the Nelson estuary, proximity to the fresh-salt
      water mixing area may be more important than the shallow waters of the upper
      estuary. Killer whales (Orcinus orca) were observed in the Churchill area (200 km
      northwest) during each year of study, 2002-05, and belugas may benefit from the
      proximity to shallow estuary waters that provide protection from the larger
      bodied predator. Study results contribute to an understanding of the influence of
      environmental variation on how and why belugas use estuaries although
      considerable uncertainties exist and additional research is required.

PMID- 28767656
TI  - Collagen turnover biomarkers and systemic right ventricle remodeling in adults
      with previous atrial switch procedure for transposition of the great arteries.
AB  - BACKGROUND: Myocardial fibrosis is a potential pathophysiological mechanism
      leading to systemic right ventricular (SRV) deterioration. We hypothesize that
      circulating levels of collagen deposition markers are elevated in patients with
      SRV remodeling and this elevation may have a predictive value. METHODS: We
      prospectively evaluated 56 patients with D-TGA after the atrial switch procedure
      (mean age 25.6 +/- 4.8, range 18-37 years; 67% males). Serum levels of
      procollagen type III amino-terminal propeptide (PIIINP), collagen type I carboxy
      terminal telopeptide (CITP), procollagen type I N-terminal propeptide (PINP),
      matrix metalloproteinase (MMP 1, MMP 9) and a tissue inhibitor of matrix
      metalloproteinase (TIMP 1) and N-terminal pro-brain natriuretic peptide (NT-pro
      BNP) were measured and compared with healthy controls. The relationship between
      these serum markers, echocardiographic and cardiac magnetic resonance parameters
      and the outcome at a follow-up of 61 months (range, 24-85 months) was determined.
      RESULTS: Compared with the healthy control group, the study group had
      significantly higher levels of TIMP1, PIIINP, CITP, PINP and NT-pro-BNP (p<0.05,
      each). The levels of PIIINP and CITP were significantly higher among patients
      with an SRV mass index above the mean value. The level of PIIINP was
      significantly higher among patients with an SRV EDV index above the mean value.
      CITP was significantly elevated in SRV late gadolinium enhanced (LGE) positive
      patients, compared to patients without SRV LGE. MMP9 and TIMP1 predicted an
      adverse clinical outcome on univariate Cox proportional hazard survival analysis
      in addition to well proven predictors of outcome (SRV EF and NYHA). CONCLUSIONS:
      We demonstrated a pattern of altered collagen turnover adversely related with the
      indices of SRV remodeling and an adverse clinical outcome in patients with SRV.

PMID- 28767657
TI  - Maternal PTSD and corresponding neural activity mediate effects of child exposure
      to violence on child PTSD symptoms.
AB  - The aim of this study was to examine the relationship of maternal interpersonal
      violence-related posttraumatic stress disorder (IPV-PTSD), associated neural
      activity in response to mother-child relational stimuli, and child
      psychopathology indicators at child ages 12-42 months and one year later. The
      study tested the hypothesis that decreased maternal neural activity in regions
      that subserve emotion regulation would be associated with child symptoms
      associated with emotional dysregulation at both time points. Functional magnetic
      resonance imaging of 42 mothers with or without violence-exposure and associated
      IPV-PTSD were assessed. Their child's life-events and symptoms/behaviors
      indicative of high-risk subsequent PTSD diagnosis on a maternal-report
      questionnaire were measured one year later. Maternal IPV-PTSD severity was
      significantly associated with decreased ventromedial prefrontal cortex (vmPFC)
      activation in response to mother-child relational stimuli. Maternal IPV-PTSD
      severity and decreased vmPFC activation were then significantly associated with a
      child attachment disturbance at 12-42 months and symptoms/behaviors one year
      later, that were correlated with emotional dysregulation and risk for child PTSD.
      Maternal IPV-PTSD and child exposure to IPV were both predictive of child PTSD
      symptoms with maternal IPV-PTSD likely mediating the effects of child IPV
      exposure on child PTSD symptoms. These findings suggest that maternal IPV-PTSD
      severity and associated decreased vmPFC activity in response to mother-child
      relational stimuli are predictors of child psychopathology by age 12-42 months
      and one-year later. Significant findings in this paper may well be useful in
      understanding how maternal top-down cortico-limbic dysregulation promotes
      intergenerational transmission of IPV and related psychopathology and, thus
      should be targeted in treatment.

PMID- 28767658
TI  - Evaluation of antibody responses to panels of M. tuberculosis antigens as a
      screening tool for active tuberculosis in Uganda.
AB  - BACKGROUND: Improved systematic screening of high-risk groups is a key component
      of the tuberculosis (TB) elimination strategy endorsed by the World Health
      Organization (WHO). We used a multiplex microbead immunoassay to measure antibody
      responses to 28 M. tuberculosis (M.tb) antigens, and assessed whether
      combinations of antibody responses achieve accuracy thresholds required for a TB
      screening test. METHODS: A random selection of plasma samples obtained from
      consecutive HIV-negative adults who were admitted to Mulago Hospital in Kampala,
      Uganda with cough >=2 weeks' but <6 months' duration were analyzed for
      serological response to 28 M.tb antigens using an in-house multiplex microbead
      immunoassay. We compared the median difference of the antibody response to each
      antigen between patients with and without culture-confirmed TB, ranked each
      antigen according to variable importance (VIM), and assessed the sensitivity and
      specificity of combinations of antibody responses using an advanced
      classification algorithm, SuperLearner. RESULTS: Among the 237 patients included
      in the analysis, 119 (50%) were female, median age was 32 years (IQR 25, 46), and
      113 (48%) had TB. Median antibody levels to eight antigens were significantly
      different between patients with and without TB. A panel including eight of the
      top ranked antigens had a sensitivity of 90.6% (95% CI 89.4, 93.8) and a
      specificity of 88.6% (95% CI 78.2, 97.6) (Ag85B, Ag85A, Ag85C, Rv0934-P38,
      Rv3881, BfrB, Rv3873, and Rv2878c). With sensitivity constrained to be >90%,
      specificity remained close to 70% with as few as 3 antigens included in the
      panels. CONCLUSIONS: Measuring antibody responses to combinations of antigens
      could facilitate TB screening and should be further evaluated in populations
      being targeted for systematic screening.

PMID- 28767659
TI  - Mitochondrial and nuclear DNA reveals reticulate evolution in hares (Lepus spp.,
      Lagomorpha, Mammalia) from Ethiopia.
AB  - For hares (Lepus spp., Leporidae, Lagomorpha, Mammalia) from Ethiopia no
      conclusive molecular phylogenetic data are available. To provide a first
      molecular phylogenetic model for the Abyssinian Hare (Lepus habessinicus), the
      Ethiopian Hare (L. fagani), and the Ethiopian Highland Hare (L. starcki) and
      their evolutionary relationships to hares from Africa, Eurasia, and North
      America, we phylogenetically analysed mitochondrial ATPase subunit 6 (ATP6; n =
      153 / 416bp) and nuclear transferrin (TF; n = 155 / 434bp) sequences of
      phenotypically determined individuals. For the hares from Ethiopia, genotype
      composition at twelve microsatellite loci (n = 107) was used to explore both
      interspecific gene pool separation and levels of current hybridization, as has
      been observed in some other Lepus species. For phylogenetic analyses ATP6 and TF
      sequences of Lepus species from South and North Africa (L. capensis, L.
      saxatilis), the Anatolian peninsula and Europe (L. europaeus, L. timidus) were
      also produced and additional TF sequences of 18 Lepus species retrieved from
      GenBank were included as well. Median joining networks, neighbour joining,
      maximum likelihood analyses, as well as Bayesian inference resulted in similar
      models of evolution of the three species from Ethiopia for the ATP6 and TF
      sequences, respectively. The Ethiopian species are, however, not monophyletic,
      with signatures of contemporary uni- and bidirectional mitochondrial
      introgression and/ or shared ancestral polymorphism. Lepus habessinicus carries
      mtDNA distinct from South African L. capensis and North African L. capensis sensu
      lato; that finding is not in line with earlier suggestions of its conspecificity
      with L. capensis. Lepus starcki has mtDNA distinct from L. capensis and L.
      europaeus, which is not in line with earlier suggestions to include it either in
      L. capensis or L. europaeus. Lepus fagani shares mitochondrial haplotypes with
      the other two species from Ethiopia, despite its distinct phenotypic and
      microsatellite differences; moreover, it is not represented by a species-specific
      mitochondrial haplogroup, suggesting considerable mitochondrial capture by the
      other species from Ethiopia or species from other parts of Africa. Both
      mitochondrial and nuclear sequences indicate close phylogenetic relationships
      among all three Lepus species from Ethiopia, with L. fagani being surprisingly
      tightly connected to L. habessinicus. TF sequences suggest close evolutionary
      relationships between the three Ethiopian species and Cape hares from South and
      North Africa; they further suggest that hares from Ethiopia hold a position
      ancestral to many Eurasian and North American species.

PMID- 28767660
TI  - Novel co-culture plate enables growth dynamic-based assessment of contact
      independent microbial interactions.
AB  - Interactions between microbes are central to the dynamics of microbial
      communities. Understanding these interactions is essential for the
      characterization of communities, yet challenging to accomplish in practice. There
      are limited available tools for characterizing diffusion-mediated, contact
      independent microbial interactions. A practical and widely implemented technique
      in such characterization involves the simultaneous co-culture of distinct
      bacterial species and subsequent analysis of relative abundance in the total
      population. However, distinguishing between species can be logistically
      challenging. In this paper, we present a low-cost, vertical membrane, co-culture
      plate to quantify contact-independent interactions between distinct bacterial
      populations in co-culture via real-time optical density measurements. These
      measurements can be used to facilitate the analysis of the interaction between
      microbes that are physically separated by a semipermeable membrane yet able to
      exchange diffusible molecules. We show that diffusion across the membrane occurs
      at a sufficient rate to enable effective interaction between physically separate
      cultures. Two bacterial species commonly found in the cystic fibrotic lung,
      Pseudomonas aeruginosa and Burkholderia cenocepacia, were co-cultured to
      demonstrate how this plate may be implemented to study microbial interactions. We
      have demonstrated that this novel co-culture device is able to reliably generate
      real-time measurements of optical density data that can be used to characterize
      interactions between microbial species.

PMID- 28767662
TI  - Dust-concentration measurement based on Mie scattering of a laser beam.
AB  - To realize automatic measurement of the concentration of dust particles in the
      air, a theory for dust concentration measurement was developed, and a system was
      designed to implement the dust concentration measurement method based on laser
      scattering. In the study, the principle of dust concentration detection using
      laser scattering is studied, and the detection basis of Mie scattering theory is
      determined. Through simulation, the influence of the incident laser wavelength,
      dust particle diameter, and refractive index of dust particles on the scattered
      light intensity distribution are obtained for determining the scattered light
      intensity curves of single suspended dust particles under different
      characteristic parameters. A genetic algorithm was used to study the inverse
      particle size distribution, and the reliability of the measurement system design
      is proven theoretically. The dust concentration detection system, which includes
      a laser system, computer circuitry, air flow system, and control system, was then
      implemented according to the parameters obtained from the theoretical analysis.
      The performance of the designed system was evaluated. Experimental results show
      that the system performance was stable and reliable, resulting in high-precision
      automatic dust concentration measurement with strong anti-interference ability.

PMID- 28767661
TI  - Impact of stress, fear and anxiety on the nociceptive responses of larval
      zebrafish.
AB  - Both adult and larval zebrafish have been demonstrated to show behavioural
      responses to noxious stimulation but also to potentially stress- and fear or
      anxiety- eliciting situations. The pain or nociceptive response can be altered
      and modulated by these situations in adult fish through a mechanism called stress
      induced analgesia. However, this phenomenon has not been described in larval fish
      yet. Therefore, this study explores the behavioural changes in larval zebrafish
      after noxious stimulation and exposure to challenges that can trigger a stress,
      fear or anxiety reaction. Five-day post fertilization zebrafish were exposed to
      either a stressor (air emersion), a predatory fear cue (alarm substance) or an
      anxiogenic (caffeine) alone or prior to immersion in acetic acid 0.1%. Pre- and
      post-stimulation behaviour (swimming velocity and time spent active) was recorded
      using a novel tracking software in 25 fish at once. Results show that larvae
      reduced both velocity and activity after exposure to the air emersion and alarm
      substance challenges and that these changes were attenuated using etomidate and
      diazepam, respectively. Exposure to acetic acid decreased velocity and activity
      as well, whereas air emersion and alarm substance inhibited these responses,
      showing no differences between pre- and post-stimulation. Therefore, we
      hypothesize that an antinociceptive mechanism, activated by stress and/or fear,
      occur in 5dpf zebrafish, which could have prevented the larvae to display the
      characteristic responses to pain.

PMID- 28767663
TI  - Contribution of exome sequencing for genetic diagnostic in arrhythmogenic right
      ventricular cardiomyopathy/dysplasia.
AB  - BACKGROUND: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) is
      an inherited cardiomyopathy mainly caused by heterozygous desmosomal gene
      mutations, the major gene being PKP2. The genetic cause remains unknown in ~50%
      of probands with routine desmosomal gene screening. The aim of this study was to
      assess the diagnostic accuracy of whole exome sequencing (WES) in ARVC/D with
      negative genetic testing. METHODS: WES was performed in 22 patients, all without
      a mutation identified in desmosomal genes. Putative pathogenic variants were
      screened in 96 candidate genes associated with other
      cardiomyopathies/channelopathies. The sequencing coverage depth of PKP2, DSP,
      DSG2, DSC2, JUP and TMEM43 exons was compared to the mean coverage distribution
      to detect large insertions/deletions. All suspected deletions were verified by
      real-time qPCR, Multiplex-Ligation-dependent-Probe-Amplification (MLPA) and cGH
      Array. MLPA was performed in 50 additional gene-negative probands. RESULTS:
      Coverage-depth analysis from the 22 WES data identified two large heterozygous
      PKP2 deletions: one from exon 1 to 14 and one restricted to exon 4, confirmed by
      qPCR and MLPA. MLPA identified 2 additional PKP2 deletions (exon 1-7 and exon 1
      14) in 50 additional probands confirming a significant frequency of large PKP2
      deletions (5.7%) in gene-negative ARVC/D. Putative pathogenic heterozygous
      variants in EYA4, RBM20, PSEN1, and COX15 were identified in 4 unrelated
      probands. CONCLUSION: A rather high frequency (5.7%) of large PKP2 deletions,
      undetectable by Sanger sequencing, was detected as the cause of ARVC/D. Coverage
      depth analysis through next-generation sequencing appears accurate to detect
      large deletions at the same time than conventional putative mutations in
      desmosomal and cardiomyopathy-associated genes.

PMID- 28767664
TI  - Bruch's membrane thickness in relationship to axial length.
AB  - PURPOSE: To assess a potential role of Bruch's membrane (BM) in the biomechanics
      of the eye, we measured its thickness and the density of retinal pigment
      epithelium (RPE) cells in various ocular regions in eyes of varying axial length.
      METHODS: Human globes, enucleated because of an ocular tumor or end-stage
      glaucoma were prepared for histological examination. Using light microscopy, the
      histological slides were histomorphometrically examined applying a digitized
      image analysis system. RESULTS: The study included 104 eyes with a mean axial
      length of 27.9+/-3.2 mm (range:22.6mm-36.5mm). In eyes without congenital
      glaucoma, BM was significantly thickest (P<0.001) at the ora serrata, followed by
      the posterior pole, the midpoint between equator and posterior pole (MBEPP), and
      finally the equator. BM thickness was not significantly correlated with axial
      length (ora serrata: P = 0.93; equator:P = 0.31; MBEPP:P = 0.15; posterior pole:P
      = 0.35). RPE cell density in the pre-equatorial region (P = 0.02; regression
      coefficient r = -0.24) and in the retro-equatorial region (P = 0.03; r = -0.22)
      decreased with longer axial length, while RPE cell density at the ora serrata (P
      = 0.35), the MBEPP (P = 0.06; r = -0.19) and the posterior pole (P = 0.38) was
      not significantly correlated with axial length. Highly myopic eyes with
      congenital glaucoma showed a tendency towards lower BM thickness and lower RPE
      cell density at all locations. CONCLUSIONS: BM thickness, in contrast to scleral
      and choroidal thickness, was independent of axial length in eyes without
      congenital glaucoma. In association with an axial elongation associated decrease
      in the RPE cell density in the midperiphery, the findings support the notion of a
      biomechanical role BM may play in the process of emmetropization/myopization.

PMID- 28767665
TI  - Systematic immunohistochemical screening for mismatch repair and ERCC1 gene
      expression from colorectal cancers in China: Clinicopathological characteristics
      and effects on survival.
AB  - BACKGROUND: We performed a systematic screening of colorectal cancer (CRC)
      tissues to investigate whether mismatch repair (MMR) status and ERCC1 protein
      expression could be predictive of clinical outcomes for these patients following
      the recommendation of The Evaluation of Genomic Applications in Practice of
      Prevention (EGAPP). METHODS: The expression of four MMR genes and ERCC1 were
      assessed by immunohistochemistry (IHC) from cancer tissue samples of 2233
      consecutive CRC patients. RESULTS: We observed that most CRC patients with a
      proficient MMR (pMMR) status tended to have simultaneous ERCC1 protein expression
      (P< 0.001). Stage III CRC patients with deficient MMR (dMMR) had higher prognoses
      than the same stage patients with pMMR (DFS: 74% vs 65%, P = 0.04; OS: 79% vs
      69%, P = 0.04). Here, dMMR is also associated with poorer survival for stage II
      patients after chemotherapy (DFS: 66% vs 78%, P = 0.04). Stage II and III
      patients that were shown to express ERCC1 protein had higher DFS and OS than
      those that were deficient in expression (stage II, DFS: 83% vs 70%, P = 0.006; OS
      85% vs 73%, P = 0.02. Stage III, DFS: 67% vs56%, P = 0.03; OS: 71% vs 57%, P =
      0.04). CONCLUSIONS: Our results indicate that dMMR appeared to predictive of a
      survival benefit for stage III CRC patients. We also found the determination of
      ERCC1 expression to be useful for predicting DFS or OS for stage II and III CRC
      patients. In addition, the expression of MMR genes and ERCC1 showed a significant
      relationship.

PMID- 28767666
TI  - Mismatch repair deficient hematopoietic stem cells are preleukemic stem cells.
AB  - Whereas transformation events in hematopoietic malignancies may occur at
      different developmental stages, the initial mutation originates in hematopoietic
      stem cells (HSCs), creating a preleukemic stem cell (PLSC). Subsequent mutations
      at either stem cell or progenitor cell levels transform the PLSC into
      lymphoma/leukemia initiating cells (LIC). Thymic lymphomas have been thought to
      develop from developing thymocytes. T cell progenitors are generated from HSCs in
      the bone marrow (BM), but maturation and proliferation of T cells as well as T
      lymphomagenesis depends on both regulatory mechanisms and microenvironment within
      the thymus. We studied PLSC linked to thymic lymphomas. In this study, we use
      MSH2-/- mice as a model to investigate the existence of PLSC and the evolution of
      PLSC to LIC. Following BM transplantation, we found that MSH2-/- BM cells from
      young mice are able to fully reconstitute multiple hematopoietic lineages of
      lethally irradiated wild-type recipients. However, all recipients developed
      thymic lymphomas within three and four months post transplantation.
      Transplantation of different fractions of BM cells or thymocytes from young
      health MSH2-/- mice showed that an HSC enriched fraction always reconstituted
      hematopoiesis followed by lymphoma development. In addition, lymphomas did not
      occur in thymectomized recipients of MSH2-/- BM. These results suggest that HSCs
      with DNA repair defects such as MSH2-/- are PLSCs because they retain
      hematopoietic function, but also carry an obligate lymphomagenic potential within
      their T-cell progeny that is dependent on the thymic microenvironment.

PMID- 28767667
TI  - Uptake of a new meningitis vaccination programme amongst first-year undergraduate
      students in the United Kingdom: A cross-sectional study.
AB  - BACKGROUND: In 2015 meningococcal group W was declared endemic in the UK, with
      the meningococcal ACWY vaccination (MenACWY) subsequently introduced amongst
      adolescents and first-year university students. This study aimed to determine
      MenACWY uptake amongst students and to evaluate how this was influenced by
      demographics and via the Health Belief Model (HBM). METHODS: This was a cross
      sectional study conducted at a British university amongst first-year
      undergraduate students aged 18-25 years. Data collection was via an electronic
      questionnaire encompassing demographics, the HBM and vaccination status.
      Univariable analysis of the associations between demographics, health beliefs and
      vaccination was performed, followed by multiple logistic regression. RESULTS: 401
      participants were included in analysis. Vaccine uptake was 68.1%. Variables
      independently associated with vaccination upon multiple regression were age, gap
      year, perceived effectiveness of the vaccine and knowledge about risk of
      meningitis. Compared to 18 year-olds, the odds of vaccination were reduced for 19
      year-olds (aOR = 0.087, 95% CI = 0.010-0.729), 20 year-olds (aOR = 0.019, 95% CI
      = 0.002-0.161) and 21-25 year-olds (aOR = 0.003, 95% CI = <0.001-0.027). In
      contrast, taking a gap year (aOR = 2.939, 95% CI = 1.329-6.501), higher perceived
      vaccine effectiveness (aOR = 3.555, 95% CI = 1.787-7.073) and knowledge about
      meningitis risk (aOR = 2.481, 95% CI = 1.165-5.287) were independently associated
      with increased uptake. CONCLUSIONS: MenACWY uptake amongst students in this study
      and in other sources is above the national coverage for all adolescents (35.3%),
      indicating that this vaccination programme may be increasing health inequalities.
      Older students are less likely to become vaccinated due to differing vaccination
      policy in this age-group. In future, strategies that focus on specific student
      cohorts and that highlight vaccine effectiveness and the risk of meningitis
      should be considered. National evaluation of this vaccination programme is
      recommended to clarify its impact on health inequalities.

PMID- 28767668
TI  - Creative foraging: An experimental paradigm for studying exploration and
      discovery.
AB  - Creative exploration is central to science, art and cognitive development.
      However, research on creative exploration is limited by a lack of high-resolution
      automated paradigms. To address this, we present such an automated paradigm, the
      creative foraging game, in which people search for novel and valuable solutions
      in a large and well-defined space made of all possible shapes made of ten
      connected squares. Players discovered shape categories such as digits, letters,
      and airplanes as well as more abstract categories. They exploited each category,
      then dropped it to explore once again, and so on. Aligned with a prediction of
      optimal foraging theory (OFT), during exploration phases, people moved along
      meandering paths that are about three times longer than the shortest paths
      between shapes; when exploiting a category of related shapes, they moved along
      the shortest paths. The moment of discovery of a new category was usually done at
      a non-prototypical and ambiguous shape, which can serve as an experimental proxy
      for creative leaps. People showed individual differences in their search
      patterns, along a continuum between two strategies: a mercurial quick-to
      discover/quick-to-drop strategy and a thorough slow-to-discover/slow-to-drop
      strategy. Contrary to optimal foraging theory, players leave exploitation to
      explore again far before categories are depleted. This paradigm opens the way for
      automated high-resolution study of creative exploration.

PMID- 28767669
TI  - Incidence and progression of diabetic retinopathy in Sub-Saharan Africa: A five
      year cohort study.
AB  - AIMS: To describe the incidence and progression of retinopathy in people with
      diabetes in Southern Malawi over 5 years. To document visual loss in a setting
      where laser treatment is not available. METHODS: Subjects from a cohort sampled
      from a hospital-based, primary-care diabetes clinic in 2007 were traced in 2012.
      Laser treatment was not available. Modified Wisconsin grading of retinopathy was
      performed using slit lamp biomicroscopy by a single ophthalmologist in 2007 and
      using four-field mydriatic fundus photographs at an accredited reading centre in
      2012. Visual acuity was measured by Snellen chart in 2007 and by 'Early Treatment
      of Diabetic Retinopathy Study' chart in 2012. HbA1c, blood pressure, HIV status,
      urine albumin-creatinine ratio, haemoglobin and lipids were measured. RESULTS: Of
      281 subjects recruited in 2007, 135 (48%) were traced and assessed, 15 were
      confirmed dead. At follow-up (median 5.3 years) >=2 step retinopathy progression
      was observed in 48 subjects (36.4%; 95% CI 28.2-44.6). Incidence of sight
      threatening diabetic retinopathy for those with level 10 (no retinopathy) and
      level 20 (background) retinopathy at baseline, was 19.4% (11.3-27.4) and 81.3%
      (62.1-100), respectively. In multivariate analysis 2 step progression was
      associated with HbA1c (OR 1.2495%CI 1.04-1.48), and haemoglobin level (0.77, 0.62
      0.98). 25 subjects (18.8%) lost >=5 letters, 7 (5.3%) lost >=15 letters.
      CONCLUSIONS: Progression to sight threatening diabetic retinopathy from no
      retinopathy and background retinopathy was approximately 5 and 3 times that
      reported in recent European studies, respectively. Incidence of visual loss was
      high in a location where treatment was not available.

PMID- 28767670
TI  - Comparing TMS perturbations to occipital and parietal cortices in concurrent TMS
      fMRI studies-Methodological considerations.
AB  - Neglect and hemianopia are two neuropsychological syndromes that are associated
      with reduced awareness for visual signals in patients' contralesional hemifield.
      They offer the unique possibility to dissociate the contributions of retino
      geniculate and retino-colliculo circuitries in visual perception. Yet, insights
      from patient fMRI studies are limited by heterogeneity in lesion location and
      extent, long-term functional reorganization and behavioural compensation after
      stroke. Transcranial magnetic stimulation (TMS) has therefore been proposed as a
      complementary method to investigate the effect of transient perturbations on
      functional brain organization. This concurrent TMS-fMRI study applied TMS
      perturbation to occipital and parietal cortices with the aim to 'mimick' neglect
      and hemianopia. Based on the challenges and interpretational limitations of our
      own study we aim to provide tutorial guidance on how future studies should
      compare TMS to primary sensory and association areas that are governed by
      distinct computational principles, neural dynamics and functional architecture.

PMID- 28767671
TI  - Potential paraneoplastic syndromes and selected autoimmune conditions in patients
      with non-small cell lung cancer and small cell lung cancer: A population-based
      cohort study.
AB  - BACKGROUND: Little is known about the occurrence and distribution of types of
      paraneoplastic syndromes (PNS) in patients with lung cancer. Identification of
      autoimmune PNS is particularly important for discerning them from immune-related
      adverse events of novel immunotherapies. We estimated the occurrence of PNS among
      patients with lung cancer and compared it with that in the general population.
      METHODS: In this registry-based cohort study in Denmark, we identified all
      patients with incident primary lung cancer between 1997 and 2010, and in a
      general-population comparison cohort matched on calendar time, sex, age, and
      residence. Among patients with non-small cell lung cancer (NSCLC) and small-cell
      lung cancer (SCLC), we estimated prevalence of potential PNS and selected
      autoimmune conditions and compared their incidence rates with those of equivalent
      conditions in the general population cohort, using hazard ratios (HRs) adjusted
      for baseline comorbidity. RESULTS: There were 35,319 patients with NSCLC and
      6,711 patients with SCLC. The incidence rates per 1000 person-years (95%
      confidence interval) of any potential PNS or selected autoimmune disorders were
      135.4 (131.9-139.1) among NSCLC patients and 237.3 (224.4-250.5) among SCLC
      patients. Adjusted HRs for any potential PNS or selected autoimmune disorders
      were 4.8 (4.7-5.0) for NSCLC and 8.2 (7.6-8.8) for SCLC. CONCLUSION: Incidence
      rate of any potential PNS or selected autoimmune disorders among patients with
      lung cancer was greater than that in the general population and was greater after
      SCLC than after NSCLC. IMPACT: These results provide context to discerning PNS
      from adverse effects of novel immunotherapies during the clinical course of NSCLC
      and SCLC.

PMID- 28767672
TI  - Bi-stability in type 2 diabetes mellitus multi-organ signalling network.
AB  - Type 2 diabetes mellitus (T2DM) is believed to be irreversible although no
      component of the pathophysiology is irreversible. We show here with a network
      model that the apparent irreversibility is contributed by the structure of the
      network of inter-organ signalling. A network model comprising all known inter
      organ signals in T2DM showed bi-stability with one insulin sensitive and one
      insulin resistant attractor. The bi-stability was made robust by multiple
      positive feedback loops suggesting an evolved allostatic system rather than a
      homeostatic system. In the absence of the complete network, impaired insulin
      signalling alone failed to give a stable insulin resistant or hyperglycemic
      state. The model made a number of correlational predictions many of which were
      validated by empirical data. The current treatment practice targeting obesity,
      insulin resistance, beta cell function and normalization of plasma glucose failed
      to reverse T2DM in the model. However certain behavioural and neuro-endocrine
      interventions ensured a reversal. These results suggest novel prevention and
      treatment approaches which need to be tested empirically.

PMID- 28767673
TI  - White-nose syndrome pathology grading in Nearctic and Palearctic bats.
AB  - While white-nose syndrome (WNS) has decimated hibernating bat populations in the
      Nearctic, species from the Palearctic appear to cope better with the fungal skin
      infection causing WNS. This has encouraged multiple hypotheses on the mechanisms
      leading to differential survival of species exposed to the same pathogen. To
      facilitate intercontinental comparisons, we proposed a novel pathogenesis-based
      grading scheme consistent with WNS diagnosis histopathology criteria. UV light
      guided collection was used to obtain single biopsies from Nearctic and Palearctic
      bat wing membranes non-lethally. The proposed scheme scores eleven grades
      associated with WNS on histopathology. Given weights reflective of grade
      severity, the sum of findings from an individual results in weighted cumulative
      WNS pathology score. The probability of finding fungal skin colonisation and
      single, multiple or confluent cupping erosions increased with increase in
      Pseudogymnoascus destructans load. Increasing fungal load mimicked progression of
      skin infection from epidermal surface colonisation to deep dermal invasion.
      Similarly, the number of UV-fluorescent lesions increased with increasing
      weighted cumulative WNS pathology score, demonstrating congruence between WNS
      associated tissue damage and extent of UV fluorescence. In a case report, we
      demonstrated that UV-fluorescence disappears within two weeks of euthermy. Change
      in fluorescence was coupled with a reduction in weighted cumulative WNS pathology
      score, whereby both methods lost diagnostic utility. While weighted cumulative
      WNS pathology scores were greater in the Nearctic than Palearctic, values for
      Nearctic bats were within the range of those for Palearctic species. Accumulation
      of wing damage probably influences mortality in affected bats, as demonstrated by
      a fatal case of Myotis daubentonii with natural WNS infection and healing in
      Myotis myotis. The proposed semi-quantitative pathology score provided good
      agreement between experienced raters, showing it to be a powerful and widely
      applicable tool for defining WNS severity.

PMID- 28767674
TI  - Versatile ion S5XL sequencer for targeted next generation sequencing of solid
      tumors in a clinical laboratory.
AB  - BACKGROUND: Next generation sequencing based tumor tissue genotyping involves
      complex workflow and a relatively longer turnaround time. Semiconductor based
      next generation platforms varied from low throughput Ion PGM to high throughput
      Ion Proton and Ion S5XL sequencer. In this study, we compared Ion PGM and Ion
      Proton, with a new Ion S5XL NGS system for workflow scalability, analytical
      sensitivity and specificity, turnaround time and sequencing performance in a
      clinical laboratory. METHODS: Eighteen solid tumor samples positive for various
      mutations as detected previously by Ion PGM and Ion Proton were selected for
      study. Libraries were prepared using DNA (range10-40ng) from micro-dissected
      formalin-fixed, paraffin-embedded (FFPE) specimens using the Ion Ampliseq Library
      Kit 2.0 for comprehensive cancer (CCP), oncomine comprehensive cancer (OCP) and
      cancer hotspot panel v2 (CHPv2) panel as per manufacturer's instructions. The
      CHPv2 were sequenced using Ion PGM whereas CCP and OCP were sequenced using Ion
      Proton respectively. All the three libraries were further sequenced individually
      (S540) or multiplexed (S530) using Ion S5XL. For S5XL, Ion chef was used to
      automate template preparation, enrichment of ion spheres and chip loading. Data
      analysis was performed using Torrent Suite 4.6 software on board S5XL and Ion
      Reporter. A limit of detection and reproducibility studies was performed using
      serially diluted DLD1 cell line. RESULTS: A total of 241 variant calls (235
      single nucleotide variants and 6 indels) expected in the studied cohort were
      successfully detected by S5XL with 100% and 97% concordance with Ion PGM and
      Proton, respectively. Sequencing run time was reduced from 4.5 to 2.5 hours with
      output range of 3-5 GB (S530) and 8-9.3Gb (S540). Data analysis time for the Ion
      S5XL is faster 1 h (S520), 2.5 h (S530) and 5 h (S540) chip, respectively as
      compared to the Ion PGM (3.5-5 h) and Ion Proton (8h). A limit detection of 5%
      allelic frequency was established along with high inter-run reproducibility.
      CONCLUSION: Ion S5XL system simplified workflow in a clinical laboratory, was
      feasible for running smaller and larger panels on the same instrument, had a
      shorter turnaround time, and showed good concordance for variant calls with
      similar sensitivity and reproducibility as the Ion PGM and Proton.

PMID- 28767675
TI  - Large-scale identification of Gossypium hirsutum genes associated with
      Verticillium dahliae by comparative transcriptomic and reverse genetics analysis.
AB  - Verticillium wilt is a devastating disease of cotton, which is caused by the soil
      borne fungus Verticillium dahliae (V. dahliae). Although previous studies have
      identified some genes or biological processes involved in the interaction between
      cotton and V. dahliae, its underlying molecular mechanism remains unclear,
      especially in G. hirsutum. In the present study, we obtained an overview of
      transcriptome characteristics of resistant upland cotton (G. hirsutum) after V.
      dahliae infection at 24 h post-inoculation (hpi) via a high-throughput RNA
      sequencing technique. A total of 4,794 differentially expressed genes (DEGs) were
      identified, including 820 up-regulated genes and 3,974 down-regulated genes. The
      enrichment analysis showed that several important processes were induced upon V.
      dahliae infection, such as plant hormone signal transduction, plant-pathogen
      interaction, phenylpropanoid-related and ubiquitin-mediated signals. Moreover, we
      investigated some key regulatory gene families involved in the defense response,
      such as receptor-like protein kinases (RLKs), WRKY transcription factors and
      cytochrome P450 (CYPs), via virus-induced gene silencing (VIGS). GhSKIP35, a
      partner of SKP1 protein, was involved in ubiquitin-mediated signal. Over
      expression of GhSKIP35 in Arabidopsis improved its tolerance to Verticillium wilt
      in transgenic plants. Collectively, global transcriptome analysis and functional
      gene characterization provided significant insights into the molecular mechanisms
      of G. hirsutum-V. dahliae interaction and offered a number of candidate genes as
      potential sources for breeding wilt-tolerance in cotton.

PMID- 28767676
TI  - Salivary flow and xerostomia in older patients with type 2 diabetes mellitus.
AB  - OBJECTIVES: To assess salivary flow in older patients with type 2 diabetes
      mellitus (DM2) and its association with xerostomia. METHODS: Cross-sectional
      clinical study conducted with older patients diagnosed with type 2 diabetes for
      at least one year receiving treatment at the Integrated Center for Diabetes and
      Hypertension of Ceara (CIHD) in the city of Fortaleza, Ceara, Northeastern
      Brazil. Oral clinical examination was carried out to assess the decayed, missing
      and filled teeth index (DMFT). Perception of the presence of xerostomia/dry mouth
      was assessed using the Visual Analogue Scale. Stimulated salivary flow was
      measured and samples were obtained using an extra-soft silicone device. RESULTS:
      120 older patients with diabetes (60 insulin-dependent and 60 non-insulin
      dependent) aged 65-91 years, with a mean age of 72.26 +/- 6.53 years, were
      assessed. Of these, 111 (92.5%) presented a decrease in salivary flow while 59
      (49.2%) reported moderate to severe xerostomia/dry mouth. The DMFT Index
      presented a mean of 27.53 +/- 4.86 teeth. CONCLUSIONS: Reduced salivary flow was
      found in the group assessed in the present research; however, this finding is not
      in accordance with the perception of xerostomia/dry mouth reported by the
      patients.

PMID- 28767677
TI  - Limited trophic partitioning among sympatric delphinids off a tropical oceanic
      atoll.
AB  - Understanding trophic relationships among marine predators in remote environments
      is challenging, but it is critical to understand community structure and
      dynamics. In this study, we used stable isotope analysis of skin biopsies to
      compare the isotopic, and thus, trophic niches of three sympatric delphinids in
      the waters surrounding Palmyra Atoll, in the Central Tropical Pacific: the melon
      headed whale (Peponocephala electra), Gray's spinner dolphin (Stenella
      longirostris longirostris), and the common bottlenose dolphin (Tursiops
      truncatus). delta15N values suggested that T. truncatus occupied a significantly
      higher trophic position than the other two species. delta13C values did not
      significantly differ between the three delphinds, potentially indicating no
      spatial partitioning in depth or distance from shore in foraging among species.
      The dietary niche area-determined by isotopic variance among individuals-of T.
      truncatus was also over 30% smaller than those of the other species taken at the
      same place, indicating higher population specialization or lower interindividual
      variation. For P. electra only, there was some support for intraspecific
      variation in foraging ecology across years, highlighting the need for temporal
      information in studying dietary niche. Cumulatively, isotopic evidence revealed
      surprisingly little evidence for trophic niche partitioning in the delphinid
      community of Palmyra Atoll compared to other studies. However, resource
      partitioning may happen via other behavioral mechanisms, or prey abundance or
      availability may be adequate to allow these three species to coexist without any
      such partitioning. It is also possible that isotopic signatures are inadequate to
      detect trophic partitioning in this environment, possibly because isotopes of
      prey are highly variable or insufficiently resolved to allow for differentiation.

PMID- 28767678
TI  - Pharmacoperone rescue of vasopressin 2 receptor mutants reveals unexpected
      constitutive activity and coupling bias.
AB  - Pharmacoperones are small molecules that diffuse into cells and rescue misfolded,
      mistrafficked protein mutants, restoring their function. These substances act
      with high target specificity, serving as templates to fold (or refold) receptors,
      enzymes, ion channels or other proteins and enable them to pass the scrutiny of
      the cellular quality control system ("rescue"). In the present study we
      demonstrate that a rescued mutant (L83Q) of the vasopressin type 2 receptor
      (V2R), shows a strong bias for Gs coupling unlike the WT V2 receptor, which
      couples to both Gs and Gq/11. Failure of the mutant to couple to Gq/11 was not
      due to a limiting quantity of G-proteins since other Gq/11-coupled receptors (WT
      V2R, histamine receptor and muscarinic receptor) responded appropriately to their
      ligands. Transfection with DNA encoding Gq enabled the V2 receptor mutant to
      couple to this G protein, but only modestly compared with the WT receptor.
      Fourteen V2R mutant pharmacoperones, of multiple chemical classes, obtained from
      a high throughput screen of a 660,000 structure library, and one V2R
      peptidomimetic antagonist rescues L83Q. The rescued mutant shows similar bias
      with all pharmacoperones identified, suggesting that the bias is intrinsic to the
      mutant protein's structure, rather than due to the chemical class of the
      pharmacoperone. In the case of V2R mutant Y128S, rescue with a pharmacoperone
      revealed constitutive activity, also with bias for Gs, although both IP and cAMP
      were produced in response to agonist. These results suggest that particular
      rescued receptor mutants show functional characteristics that differ from the WT
      receptor; a finding that may be important to consider as pharmacoperones are
      developed as therapeutic agents.

PMID- 28767679
TI  - Compartmentalized metabolic network reconstruction of microbial communities to
      determine the effect of agricultural intervention on soils.
AB  - Soil microbial communities are responsible for a wide range of ecological
      processes and have an important economic impact in agriculture. Determining the
      metabolic processes performed by microbial communities is crucial for
      understanding and managing ecosystem properties. Metagenomic approaches allow the
      elucidation of the main metabolic processes that determine the performance of
      microbial communities under different environmental conditions and perturbations.
      Here we present the first compartmentalized metabolic reconstruction at a
      metagenomics scale of a microbial ecosystem. This systematic approach conceives a
      meta-organism without boundaries between individual organisms and allows the in
      silico evaluation of the effect of agricultural intervention on soils at a
      metagenomics level. To characterize the microbial ecosystems, topological
      properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis
      (FBA) were considered. Furthermore, topological and optimization algorithms were
      implemented to carry out the curation of the models, to ensure the continuity of
      the fluxes between the metabolic pathways, and to confirm the metabolite exchange
      between subcellular compartments. The proposed models provide specific
      information about ecosystems that are generally overlooked in non
      compartmentalized or non-curated networks, like the influence of transport
      reactions in the metabolic processes, especially the important effect on
      mitochondrial processes, as well as provide more accurate results of the fluxes
      used to optimize the metabolic processes within the microbial community.

PMID- 28767680
TI  - Thoracoabdominal asynchrony: Two methods in healthy, COPD, and interstitial lung
      disease patients.
AB  - BACKGROUND: Thoracoabdominal asynchrony is the nonparallel motion of the ribcage
      and abdomen. It is estimated by using respiratory inductive plethysmography and,
      recently, using optoelectronic plethysmography; however the agreement of
      measurements between these 2 techniques is unknown. Therefore, the present study
      compared respiratory inductive plethysmography with optoelectronic
      plethysmography for measuring thoracoabdominal asynchrony to see if the
      measurements were similar or different. METHODS: 27 individuals (9 healthy
      subjects, 9 patients with interstitial lung disease, and 9 with chronic
      obstructive pulmonary disease performed 2 cycle ergometer tests with respiratory
      inductive plethysmography or optoelectronic plethysmography in a random order.
      Thoracoabdominal asynchrony was evaluated at rest, and at 50% and 75% of maximal
      workload between the superior ribcage and abdomen using a phase angle. RESULTS:
      Thoracoabdominal asynchrony values were very similar in both approaches not only
      at rest but also with exercise, with no statistical difference. There was a good
      correlation between the methods and the Phase angle values were within the limits
      of agreement in the Bland-Altman analysis. CONCLUSION: Thoracoabdominal
      asynchrony measured by optoelectronic plethysmography and respiratory inductive
      plethysmography results in similar values and has a satisfactory agreement at
      rest and even for different exercise intensities in these groups.

PMID- 28767681
TI  - Study of three interesting Amanita species from Thailand: Morphology, multiple
      gene phylogeny and toxin analysis.
AB  - Amanita ballerina and A. brunneitoxicaria spp. nov. are introduced from Thailand.
      Amanita fuligineoides is also reported for the first time from Thailand,
      increasing the known distribution of this taxon. Together, those findings support
      our view that many taxa are yet to be discovered in the region. While both
      morphological characters and a multiple-gene phylogeny clearly place A.
      brunneitoxicaria and A. fuligineoides in sect. Phalloideae (Fr.) Quel., the
      placement of A. ballerina is problematic. On the one hand, the morphology of A.
      ballerina shows clear affinities with stirps Limbatula of sect. Lepidella. On the
      other hand, in a multiple-gene phylogeny including taxa of all sections in subg.
      Lepidella, A. ballerina and two other species, including A. zangii, form a well
      supported clade sister to the Phalloideae sensu Bas 1969, which include the
      lethal "death caps" and "destroying angels". Together, the A. ballerina-A. zangii
      clade and the Phalloideae sensu Bas 1969 also form a well-supported clade. We
      therefore screened for two of the most notorious toxins by HPLC-MS analysis of
      methanolic extracts from the basidiomata. Interestingly, neither alpha-amanitin
      nor phalloidin was found in A. ballerina, whereas Amanita fuligineoides was
      confirmed to contain both alpha-amanitin and phalloidin, and A. brunneitoxicaria
      contained only alpha-amanitin. Together with unique morphological
      characteristics, the position in the phylogeny indicates that A. ballerina is
      either an important link in the evolution of the deadly Amanita sect. Phalloideae
      species, or a member of a new section also including A. zangii.

PMID- 28767682
TI  - Genetic variability and functional implication of the long control region in HPV
      16 variants in Southwest China.
AB  - HPV-16 long control region (LCR) has been shown to be the most variable region of
      the HPV-16 genome and may play important roles in viral persistence and the
      development of cervical cancer. This study aimed to assess the risk of HPV-16 LCR
      variants for cervical cancer in women of Southwest China. 2146 cervical scrapings
      of volunteer outpatients and 74 cervical cancer tissues were screened.14 entire
      HPV-16 LCRs from asymptomatic carriers and 34 entire HPV-16 LCRs from cervical
      cancer patients were successfully amplified and sequenced to align to others
      described. 58 different point mutations were detected in 54 nucleotide sites of
      HPV-16 LCR. G7193T and G7521A variants, accounting for 100% of the infections,
      were predicted to locate at the binding site for FOXA1 and SOX9, respectively.
      A7730C variant which showed a high mutation frequency in cervical cancer was
      predicted to be a binding site for the cellular transcription factor PHOX2A. In
      addition, phylogenetic analysis displayed a high prevalence of A lineage in HPV
      16 LCR in this Southwest China population. This study may help understanding of
      the intrinsic geographical relatedness and the correlations between LCR mutations
      and the development of carcinogenic lesions in Southwest China population. And it
      provides useful data for the further study of the biological function of HPV-16
      LCR variants.

PMID- 28767683
TI  - Quantifying kinematic differences between land and water during squats, split
      squats, and single-leg squats in a healthy population.
AB  - Aquatic exercises can be used in clinical and sporting disciplines for both
      rehabilitation and sports training. However, there is limited knowledge on the
      influence of water immersion on the kinematics of exercises commonly used in
      rehabilitation and fitness programs. The aim of this study was to use inertial
      sensors to quantify differences in kinematics and movement variability of
      bodyweight squats, split squats, and single-leg squats performed on dry land and
      whilst immersed to the level of the greater trochanter. During two separate
      testing sessions, 25 active healthy university students (22.3+/-2.9 yr.)
      performed ten repetitions of each exercise, whilst tri-axial inertial sensors
      (100 Hz) recorded their trunk and lower body kinematics. Repeated-measures
      statistics tested for differences in segment orientation and speed, movement
      variability, and waveform patterns between environments, while coefficient of
      variance was used to assess differences in movement variability. Between
      environment differences in segment orientation and speed were portrayed by
      plotting the mean difference +/-95% confidence intervals (CI) throughout the
      tasks. The results showed that the depth of the squat and split squat were
      unaffected by the changed environment while water immersion allowed for a deeper
      single leg squat. The different environments had significant effects on the
      sagittal plane orientations and speeds for all segments. Water immersion
      increased the degree of movement variability of the segments in all exercises,
      except for the shank in the frontal plane, which showed more variability on land.
      Without compromising movement depth, the aquatic environment induces more upright
      trunk and shank postures during squats and split squats. The aquatic environment
      allows for increased squat depth during the single-leg squat, and increased shank
      motions in the frontal plane. Our observations therefore support the use of water
      based squat tasks for rehabilitation as they appear to improve the technique
      without compromising movement depth.

PMID- 28767684
TI  - Application of chronic liver failure-sequential organ failure assessment score
      for the predication of mortality after esophageal variceal hemorrhage post
      endoscopic ligation.
AB  - BACKGROUND: Esophageal variceal hemorrhage (EVH) is one of the high mortality
      complications in cirrhotic patients. Endoscopic variceal ligation (EVL) is
      currently the standard therapy for EVH. However, some patients have expired
      during hospitalization or survived shortly after management. AIM: To evaluate
      hospital and 6-week mortality by receiver operating characteristic (ROC) curve of
      chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score
      compared to a model for end-stage liver disease (MELD) score and Child-Turcotte
      Pugh (CTP) class. METHODS: We retrospectively collected 714 cirrhotic patients
      with EVH post EVL between July 2010 and June 2016 at Taitung MacKay Memorial
      Hospital, Taiwan. CLIF-SOFA score, MELD score, and CTP class were calculated for
      all patients admitted. RESULTS: Among the 714 patients, the overall hospital and
      6-week mortality rates were 6.9% (49/715) and 13.1% (94/715) respectively. For
      predicting hospital death, area under receiver operating characteristic curve
      (AUROC) values of CLIF-SOFA score, MELD score, and CTP class were 0.964, 0.876,
      and 0.846. For predicting 6-week death, AUROC values of CLIF-SOFA score, MELD
      score, and CTP class were 0.943, 0.817, and 0.834. CLIF-SOFA score had higher
      AUROC value with statistical significance under pairwise comparison than did MELD
      score and CTP class in prediction of not only hospital but also 6-week mortality.
      The history of hepatocellular carcinoma was the risk factor for 6-week mortality.
      For patients with hepatocellular carcinoma the cut-point of CLIF-SOFA score was
      5.5 for 6-week mortality and 6.5 for hospital mortality on admission. For
      patients without hepatocellular carcinoma, the cut-point of CLIF-SOFA score was
      6.5 for both 6-week and hospital mortality. CONCLUSION: CLIF-SOFA score predicted
      post-EVL prognosis well. For patients without hepatocellular carcinoma, CLIF-SOFA
      score >=6 suggests higher 6-week mortality and CLIF-SOFA score >=7 suggests
      higher hospital mortality. For patients with hepatocellular carcinoma, CLIF-SOFA
      score >=7 suggests higher 6-week and hospital mortality.

PMID- 28767685
TI  - Histone deacetylase inhibition prevents cell death induced by loss of tricellular
      tight junction proteins in temperature-sensitive mouse cochlear cells.
AB  - Tricellular tight junctions (tTJs) are specialized structures that occur where
      the corners of three cells meet to seal adjacent intercellular space. The
      molecular components of tTJs include tricellulin (TRIC) and lipolysis-stimulated
      lipoprotein receptor (LSR) which recruits TRIC, are required for normal hearing.
      Although loss of TRIC causes hearing loss with degeneration of cochlear cells,
      the detailed mechanisms remains unclear. In the present study, by using
      temperature-sensitive mouse cochlear cells, US/VOT-E36 cell line, we investigated
      the changes of TRIC and LSR during cochlear cell differentiation and the effects
      of histone deacetylase (HDAC) inhibitors against cell degeneration induced by
      loss of TRIC and LSR. During cell differentiation induced by the temperature
      change, expression of TRIC and LSR were clearly induced. Treatment with metformin
      enhanced expression TRIC and LSR via AMPK during cell differentiation. Loss of
      TRIC and LSR by the siRNAs induced cell death in differentiated cells. Treatment
      with HDAC inhibitors trichostatin A and HDAC6 inhibitor prevented the cell death
      induced by loss of TRIC and LSR. Collectively, these findings suggest that both
      tTJ proteins TRIC and LSR have crucial roles for the differentiated cochlear cell
      survival, and that HDAC inhibitors may be potential therapeutic agents to prevent
      hearing loss.

PMID- 28767686
TI  - Structure and properties of the egg mass of the ommastrephid squid Todarodes
      pacificus.
AB  - The Japanese flying squid, Todarodes pacificus, is thought to spawn neutrally
      buoyant egg masses that retain a specific location in the water column by
      floating at the interface between water layers of slightly different densities.
      It is important to understand the physical process that determines the vertical
      distribution of the egg masses to predict their horizontal drift in relation to
      embryo survival and subsequent recruitment. Here, mesocosm experiments were
      conducted in a 300 m3 tank by creating a thermally stratified (17-22 degrees C)
      water column to obtain egg masses. A cage net methodology was developed to
      sustain egg masses for detailed observation. We measured the density of the egg
      masses of T. pacificus, and used this information to infer the vertical
      distribution patterns of the egg masses at the spawning grounds (Tsushima Strait,
      Japan). When measured separately, the density of the outer jelly of each egg mass
      was 2.7 sigma units higher than that of the surrounding water. The outer jelly
      and the specific gravity of embedded individual eggs (~1.10) cause the egg masses
      to have very slight negative buoyancy relative to the water in which they are
      formed. Analysis of the vertical profile of the spawning ground showed that water
      density (sigmatheta) increased sharply at ~30 m depth; thus, egg masses might
      settle above the pycnocline layer. In conclusion, we suggest that T. pacificus
      egg masses might retain their location in the water column by floating at the
      interface between water layers of slightly different densities, which happen to
      be above the pycnocline layer (actual depth varies seasonally/annually) in the
      Tsushima Strait between Korea and Japan.

PMID- 28767687
TI  - A novel on-line spatial-temporal k-anonymity method for location privacy
      protection from sequence rules-based inference attacks.
AB  - Analyzing large-scale spatial-temporal k-anonymity datasets recorded in location
      based service (LBS) application servers can benefit some LBS applications.
      However, such analyses can allow adversaries to make inference attacks that
      cannot be handled by spatial-temporal k-anonymity methods or other methods for
      protecting sensitive knowledge. In response to this challenge, first we defined a
      destination location prediction attack model based on privacy-sensitive sequence
      rules mined from large scale anonymity datasets. Then we proposed a novel on-line
      spatial-temporal k-anonymity method that can resist such inference attacks. Our
      anti-attack technique generates new anonymity datasets with awareness of privacy
      sensitive sequence rules. The new datasets extend the original sequence database
      of anonymity datasets to hide the privacy-sensitive rules progressively. The
      process includes two phases: off-line analysis and on-line application. In the
      off-line phase, sequence rules are mined from an original sequence database of
      anonymity datasets, and privacy-sensitive sequence rules are developed by
      correlating privacy-sensitive spatial regions with spatial grid cells among the
      sequence rules. In the on-line phase, new anonymity datasets are generated upon
      LBS requests by adopting specific generalization and avoidance principles to hide
      the privacy-sensitive sequence rules progressively from the extended sequence
      anonymity datasets database. We conducted extensive experiments to test the
      performance of the proposed method, and to explore the influence of the parameter
      K value. The results demonstrated that our proposed approach is faster and more
      effective for hiding privacy-sensitive sequence rules in terms of hiding
      sensitive rules ratios to eliminate inference attacks. Our method also had fewer
      side effects in terms of generating new sensitive rules ratios than the
      traditional spatial-temporal k-anonymity method, and had basically the same side
      effects in terms of non-sensitive rules variation ratios with the traditional
      spatial-temporal k-anonymity method. Furthermore, we also found the performance
      variation tendency from the parameter K value, which can help achieve the goal of
      hiding the maximum number of original sensitive rules while generating a minimum
      of new sensitive rules and affecting a minimum number of non-sensitive rules.

PMID- 28767688
TI  - Cross-reaction between Formosan termite (Coptotermes formosanus) proteins and
      cockroach allergens.
AB  - Cockroach allergens can lead to serious allergy and asthma symptoms. Termites are
      evolutionarily related to cockroaches, cohabitate in human dwellings, and
      represent an increasing pest problem in the United States. The Formosan
      subterranean termite (Coptotermes formosanus) is one of the most common species
      in the southern United States. Several assays were used to determine if C.
      formosanus termite proteins cross-react with cockroach allergens. Expressed
      sequence tag and genomic sequencing results were searched for homology to
      cockroach allergens using BLAST 2.2.21 software. Whole termite extracts were
      analyzed by mass-spectrometry, immunoassay with IgG and scFv antibodies to
      cockroach allergens, and human IgE from serum samples of cockroach allergic
      patients. Expressed sequence tag and genomic sequencing results indicate greater
      than 60% similarity between predicted termite proteins and German and American
      cockroach allergens, including Bla g 2/Per a 2, Bla g 3/Per a 3, Bla g 5, Bla g
      6/Per a 6, Bla g 7/Per a 7, Bla g 8, Per a 9, and Per a 10. Peptides from whole
      termite extract were matched to those of the tropomyosin (Bla g 7), arginine
      kinase (Per a 9), and myosin (Bla g 8) cockroach allergens by mass-spectrometry.
      Immunoblot and ELISA testing revealed cross-reaction between several proteins
      with IgG and IgE antibodies to cockroach allergens. Several termite proteins,
      including the hemocyanin and tropomyosin orthologs of Blag 3 and Bla g 7, were
      shown to crossreact with cockroach allergens. This work presents support for the
      hypothesis that termite proteins may act as allergens and the findings could be
      applied to future allergen characterization, epitope analysis, and clinical
      studies.

PMID- 28767689
TI  - CRISPRpred: A flexible and efficient tool for sgRNAs on-target activity
      prediction in CRISPR/Cas9 systems.
AB  - The CRISPR/Cas9-sgRNA system has recently become a popular tool for genome
      editing and a very hot topic in the field of medical research. In this system,
      Cas9 protein is directed to a desired location for gene engineering and cleaves
      target DNA sequence which is complementary to a 20-nucleotide guide sequence
      found within the sgRNA. A lot of experimental efforts, ranging from in vivo
      selection to in silico modeling, have been made for efficient designing of sgRNAs
      in CRISPR/Cas9 system. In this article, we present a novel tool, called
      CRISPRpred, for efficient in silico prediction of sgRNAs on-target activity which
      is based on the applications of Support Vector Machine (SVM) model. To conduct
      experiments, we have used a benchmark dataset of 17 genes and 5310 guide
      sequences where there are only 20% true values. CRISPRpred achieves Area Under
      Receiver Operating Characteristics Curve (AUROC-Curve), Area Under Precision
      Recall Curve (AUPR-Curve) and maximum Matthews Correlation Coefficient (MCC) as
      0.85, 0.56 and 0.48, respectively. Our tool shows approximately 5% improvement in
      AUPR-Curve and after analyzing all evaluation metrics, we find that CRISPRpred is
      better than the current state-of-the-art. CRISPRpred is enough flexible to
      extract relevant features and use them in a learning algorithm. The source code
      of our entire software with relevant dataset can be found in the following link:
      https://github.com/khaled-buet/CRISPRpred.

PMID- 28767690
TI  - A simplified prevention bundle with dual hand hygiene audit reduces early-onset
      ventilator-associated pneumonia in cardiovascular surgery units: An interrupted
      time-series analysis.
AB  - BACKGROUND: To investigate the effect of a simplified prevention bundle with
      alcohol-based, dual hand hygiene (HH) audit on the incidence of early-onset
      ventilation-associated pneumonia (VAP). METHODS: This 3-year, quasi-experimental
      study with interrupted time-series analysis was conducted in two cardiovascular
      surgery intensive care units in a medical center. Unaware external HH audit (eHH)
      performed by non-unit-based observers was a routine task before and after bundle
      implementation. Based on the realistic ICU settings, we implemented a 3-component
      bundle, which included: a compulsory education program, a knowing internal HH
      audit (iHH) performed by unit-based observers, and a standardized oral care (OC)
      protocol with 0.1% chlorhexidine gluconate. The study periods comprised 4 phases:
      12-month pre-implementation phase 1 (eHH+/education-/iHH-/OC-), 3-month run-in
      phase 2 (eHH+/education+/iHH+/OC+), 15-month implementation phase 3
      (eHH+/education+/iHH+/OC+), and 6-month post-implementation phase 4
      (eHH+/education-/iHH+/OC-). RESULTS: A total of 2553 ventilator-days were
      observed. VAP incidences (events/1000 ventilator days) in phase 1-4 were 39.1,
      40.5, 15.9, and 20.4, respectively. VAP was significantly reduced by 59% in phase
      3 (vs. phase 1, incidence rate ratio [IRR] 0.41, P = 0.002), but rebounded in
      phase 4. Moreover, VAP incidence was inversely correlated to compliance of OC (r2
      = 0.531, P = 0.001) and eHH (r2 = 0.878, P < 0.001), but not applied for iHH,
      despite iHH compliance was higher than eHH compliance during phase 2 to 4.
      Compared to eHH, iHH provided more efficient and faster improvements for standard
      HH practice. The minimal compliances required for significant VAP reduction were
      85% and 75% for OC and eHH (both P < 0.05, IRR 0.28 and 0.42, respectively).
      CONCLUSIONS: This simplified prevention bundle effectively reduces early-onset
      VAP incidence. An unaware HH compliance correlates with VAP incidence. A knowing
      HH audit provides better improvement in HH practice. Accordingly, we suggest dual
      HH audit and consistent bundle performance does matter in quality-of-care VAP
      prevention.

PMID- 28767691
TI  - CRISPR/Cas9-mediated knockout of c-REL in HeLa cells results in profound defects
      of the cell cycle.
AB  - Cervical cancer is the fourth common cancer in women resulting worldwide in
      266,000 deaths per year. Belonging to the carcinomas, new insights into cervical
      cancer biology may also have great implications for finding new treatment
      strategies for other kinds of epithelial cancers. Although the transcription
      factor NF-kappaB is known as a key player in tumor formation, the relevance of
      its particular subunits is still underestimated. Here, we applied CRISPR/Cas9n
      mediated genome editing to successfully knockout the NF-kappaB subunit c-REL in
      HeLa Kyoto cells as a model system for cervical cancers. We successfully
      generated a homozygous deletion in the c-REL gene, which we validated using
      sequencing, qPCR, immunocytochemistry, western blot analysis, EMSA and analysis
      of off-target effects. On the functional level, we observed the deletion of c-REL
      to result in a significantly decreased cell proliferation in comparison to
      wildtype (wt) without affecting apoptosis. The impaired proliferative behavior of
      c-REL-/- cells was accompanied by a strongly decreased amount of the H2B protein
      as well as a significant delay in the prometaphase of mitosis compared to c
      REL+/+ HeLa Kyoto cells. c-REL-/- cells further showed significantly decreased
      expression levels of c-REL target genes in comparison to wt. In accordance to our
      proliferation data, we observed the c-REL knockout to result in a significantly
      increased resistance against the chemotherapeutic agents 5-Fluoro-2'-deoxyuridine
      (5-FUDR) and cisplatin. In summary, our findings emphasize the importance of c
      REL signaling in a cellular model of cervical cancer with direct clinical
      implications for the development of new treatment strategies.

PMID- 28767692
TI  - Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta
      cells.
AB  - Glucagon-like peptide-1 (GLP-1) is a potent gluco-incretin hormone, which plays a
      central role on pancreatic beta cell proliferation, survival and insulin
      secreting activity and whose analogs are used for treating hyperglycemia in type
      2 diabetes mellitus. Notably, abnormal insulin signaling affects all the above
      mentioned aspects on pancreatic beta cells. The aim of our study was to
      investigate whether the protective effects of GLP1-1 on beta cells are affected
      by altered insulin receptor signaling. To this end, several effects of GLP-1 were
      studied in INS-1E rat beta cells transfected either with an inhibitor of insulin
      receptor function (i.e., the Ectonucleotide Pyrophosphatase Phosphodiesterase 1,
      ENPP1), or with insulin receptor small interfering RNA, as well as in control
      cells. Crucial experiments were carried out also in a second cell line, namely
      the betaTC-1 mouse beta cells. Our data indicate that in insulin secreting beta
      cells in which either ENPP1 was up-regulated or insulin receptor was down
      regulated, GLP-1 positive effects on several pancreatic beta cell activities,
      including glucose-induced insulin secretion, cell proliferation and cell
      survival, were strongly reduced. Further studies are needed to understand whether
      such a scenario occurs also in humans and, if so, if it plays a role of clinical
      relevance in diabetic patients with poor responsiveness to GLP-1 related
      treatments.

PMID- 28767693
TI  - Dendritic cells that phagocytose apoptotic macrophages loaded with mycobacterial
      antigens activate CD8 T cells via cross-presentation.
AB  - While homeostatic apoptosis is immunologically silent, macrophage apoptosis
      during Mycobacterium tuberculosis infection can potentially induce an immune
      response against the mycobacteria. To examine the role of dendritic cells in this
      response, macrophage apoptosis was induced by incubating the macrophage with cell
      wall extracts of mycobacteria expressing LpqH. The apoptogenic proteins of the
      cell wall extracts were engulfed by the macrophage and then were translocated
      from the cytosol to the nuclei of the dying cells. Dendritic cells that engulfed
      the apoptotic macrophages acquired an immunogenic phenotype that included
      upregulation of MHC-I, increased expression of the costimulatory molecules, CD40,
      CD80, and CD86, and increased production of IL-12, IL-10, TNF-alpha, and TGF
      beta. In addition, the dendritic cells triggered a proliferative response of CD8+
      T cells with IFN-gamma production via cross-presentation. Taken together, these
      findings support a model in which phagocytosis of whole apoptotic cells carrying
      mycobacterial antigens promotes a potentially protective immune response.

PMID- 28767694
TI  - Group elicitations yield more consistent, yet more uncertain experts in
      understanding risks to ecosystem services in New Zealand bays.
AB  - The elicitation of expert judgment is an important tool for assessment of risks
      and impacts in environmental management contexts, and especially important as
      decision-makers face novel challenges where prior empirical research is lacking
      or insufficient. Evidence-driven elicitation approaches typically involve
      techniques to derive more accurate probability distributions under fairly
      specific contexts. Experts are, however, prone to overconfidence in their
      judgements. Group elicitations with diverse experts can reduce expert
      overconfidence by allowing cross-examination and reassessment of prior
      judgements, but groups are also prone to uncritical "groupthink" errors. When the
      problem context is underspecified the probability that experts commit groupthink
      errors may increase. This study addresses how structured workshops affect expert
      variability among and certainty within responses in a New Zealand case study. We
      find that experts' risk estimates before and after a workshop differ, and that
      group elicitations provided greater consistency of estimates, yet also greater
      uncertainty among experts, when addressing prominent impacts to four different
      ecosystem services in coastal New Zealand. After group workshops, experts
      provided more consistent ranking of risks and more consistent best estimates of
      impact through increased clarity in terminology and dampening of extreme
      positions, yet probability distributions for impacts widened. The results from
      this case study suggest that group elicitations have favorable consequences for
      the quality and uncertainty of risk judgments within and across experts, making
      group elicitation techniques invaluable tools in contexts of limited data.

PMID- 28767695
TI  - Drosophila LKB1 is required for the assembly of the polarized actin structure
      that allows spermatid individualization.
AB  - In mammals, a testis-specific isoform of the protein kinase LKB1 is required for
      spermiogenesis, but its exact function and specificity are not known. Human LKB1
      rescues the functions of Drosophila Lkb1 essential for viability, but these males
      are sterile, revealing a new function for this genes in fly. We also identified a
      testis-specific transcript generated by an alternative promoter and that only
      differs by a longer 5'UTR. We show that dLKB1 is required in the germline for the
      formation of the actin cone, the polarized structure that allows spermatid
      individualization and cytoplasm excess extrusion during spermiogenesis. Three of
      the nine LKB1 classical targets in the Drosophila genome (AMPK, NUAK and KP78b)
      are required for proper spermiogenesis, but later than dLKB1. dLkb1 mutant
      phenotype is reminiscent of that of myosin V mutants, and both proteins show a
      dynamic localization profile before actin cone formation. Together, these data
      highlight a new dLKB1 function and suggest that dLKB1 posttranscriptional
      regulation in testis and involvement in spermatid morphogenesis are
      evolutionarily conserved features.

PMID- 28767696
TI  - Analysis of SHIP1 expression and activity in Crohn's disease patients.
AB  - BACKGROUND: SH2 domain containing inositol-5-phosphatase (SHIP1) is an important
      modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe
      ileitis resembling Crohn's disease (CD), as a result of deregulated immune
      responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1
      activity was shown to be correlated to the presence of a CD-associated single
      nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and
      expression in an adult cohort of CD patients. METHODS: SHIP1 activity, protein
      and mRNA expression in peripheral blood mononuclear cells from CD patients in
      clinical remission were determined by Malachite green assay, Western blotting and
      qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880. RESULTS:
      SHIP1 protein levels are profoundly diminished in a subset of patients; however,
      SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this
      adult cohort. CONCLUSIONS: Aberrant SHIP1 activity can contribute to disease in a
      subset of adult CD patients, and warrants further investigation.

PMID- 28767697
TI  - Cyclophilin A potentiates TRIM5alpha inhibition of HIV-1 nuclear import without
      promoting TRIM5alpha binding to the viral capsid.
AB  - The host immunophilin cyclophilin A (CypA) binds to the capsid protein (CA) of
      HIV-1 and regulates its infectivity. Depending on the target cell type, CypA can
      either promote or inhibit HIV-1 infection. The ability of CypA to promote HIV-1
      infection has been extensively studied and linked to several steps in early
      replication including uncoating, reverse transcription and nuclear import. By
      contrast, the mechanism by which CypA inhibits infection is less well understood.
      We investigated the mechanism by which CypA potentiates restriction of HIV-1 by
      the tripartite motif-containing protein 5 (TRIM5alpha). Depletion of TRIM5alpha
      in the African green monkey cell line Vero, resulted in a loss of inhibition of
      infection by CypA, demonstrating that inhibition by CypA is mediated by
      TRIM5alpha. Complementary genetic and biochemical assays failed to demonstrate an
      ability of CypA to promote binding of TRIM5alpha to the viral capsid. TRIM5alpha
      inhibits HIV-1 reverse transcription in a proteasome-dependent manner; however,
      we observed that inhibition of proteasome activity did not reduce the ability of
      CypA to inhibit infection, suggesting that CypA acts at a step after reverse
      transcription. Accordingly, we observed a CypA-dependent reduction in the
      accumulation of nuclear HIV-1 DNA, indicating that CypA specifically promotes
      TRIM5alpha inhibition of HIV-1 nuclear import. We also observed that the ability
      of CypA to inhibit HIV-1 infection is abolished by amino acid substitutions
      within the conserved CPSF6-binding surface in CA. Our results indicate that CypA
      inhibits HIV-1 infection in Vero cells not by promoting TRIM5alpha binding to the
      capsid but by blocking nuclear import of the HIV-1 preintegration complex.

PMID- 28767698
TI  - Brain plasticity and sensorimotor deterioration as a function of 70 days head
      down tilt bed rest.
AB  - BACKGROUND: Adverse effects of spaceflight on sensorimotor function have been
      linked to altered somatosensory and vestibular inputs in the microgravity
      environment. Whether these spaceflight sequelae have a central nervous system
      component is unknown. However, experimental studies have shown spaceflight
      induced brain structural changes in rodents' sensorimotor brain regions.
      Understanding the neural correlates of spaceflight-related motor performance
      changes is important to ultimately develop tailored countermeasures that ensure
      mission success and astronauts' health. METHOD: Head down-tilt bed rest (HDBR)
      can serve as a microgravity analog because it mimics body unloading and headward
      fluid shifts of microgravity. We conducted a 70-day 6 degrees  HDBR study with 18
      right-handed males to investigate how microgravity affects focal gray matter (GM)
      brain volume. MRI data were collected at 7 time points before, during and post
      HDBR. Standing balance and functional mobility were measured pre and post-HDBR.
      The same metrics were obtained at 4 time points over ~90 days from 12 control
      subjects, serving as reference data. RESULTS: HDBR resulted in widespread
      increases GM in posterior parietal regions and decreases in frontal areas;
      recovery was not yet complete by 12 days post-HDBR. Additionally, HDBR led to
      balance and locomotor performance declines. Increases in a cluster comprising the
      precuneus, precentral and postcentral gyrus GM correlated with less deterioration
      or even improvement in standing balance. This association did not survive
      Bonferroni correction and should therefore be interpreted with caution. No brain
      or behavior changes were observed in control subjects. CONCLUSIONS: Our results
      parallel the sensorimotor deficits that astronauts experience post-flight. The
      widespread GM changes could reflect fluid redistribution. Additionally, the
      association between focal GM increase and balance changes suggests that HDBR also
      may result in neuroplastic adaptation. Future studies are warranted to determine
      causality and underlying mechanisms.

PMID- 28767699
TI  - Molecular evolutionary patterns of NAD+/Sirtuin aging signaling pathway across
      taxa.
AB  - A deeper understanding of the conserved molecular mechanisms in different taxa
      have been made possible only because of the evolutionary conservation of crucial
      signaling pathways. In the present study, we explored the molecular evolutionary
      pattern of selection signatures in 51 species for 10 genes which are important
      components of NAD+/Sirtuin pathway and have already been directly linked to
      lifespan extension in worms and mice. Selection pressure analysis using PAML
      program revealed that MRPS5 and PPARGC1A were under significant constraints
      because of their functional significance. FOXO3a also displayed strong purifying
      selection. All three sirtuins, which were SIRT1, SIRT2 and SIRT6, displayed a
      great degree of conservation between taxa, which is consistent with the previous
      report. A significant evolutionary constraint is seen on the anti-oxidant gene,
      SOD3. As expected, TP53 gene was under significant selection pressure in mammals,
      owing to its major role in tumor progression. Poly-ADP-ribose polymerase (PARP)
      genes displayed the most sites under positive selection. Further 3D structural
      analysis of PARP1 and PARP2 protein revealed that some of these positively
      selected sites caused a change in the electrostatic potential of the protein
      structure, which may allow a change in its interaction with other proteins and
      molecules ultimately leading to difference in the function. Although the
      functional significance of the positively selected sites could not be established
      in the variants databases, yet it will be interesting to see if these sites
      actually affect the function of PARP1 and PARP2.

PMID- 28767700
TI  - Environmental impacts of food consumption by dogs and cats.
AB  - In the US, there are more than 163 million dogs and cats that consume, as a
      significant portion of their diet, animal products and therefore potentially
      constitute a considerable dietary footprint. Here, the energy and animal-derived
      product consumption of these pets in the US is evaluated for the first time, as
      are the environmental impacts from the animal products fed to them, including
      feces production. In the US, dogs and cats consume about 19% +/- 2% of the amount
      of dietary energy that humans do (203 +/- 15 PJ yr-1 vs. 1051 +/- 9 PJ yr-1) and
      33% +/- 9% of the animal-derived energy (67 +/- 17 PJ yr-1 vs. 206 +/- 2 PJ yr
      1). They produce about 30% +/- 13%, by mass, as much feces as Americans (5.1 +/-
      Tg yr-1 vs. 17.2 Tg yr-1), and through their diet, constitute about 25-30% of the
      environmental impacts from animal production in terms of the use of land, water,
      fossil fuel, phosphate, and biocides. Dog and cat animal product consumption is
      responsible for release of up to 64 +/- 16 million tons CO2-equivalent methane
      and nitrous oxide, two powerful greenhouse gasses (GHGs). Americans are the
      largest pet owners in the world, but the tradition of pet ownership in the US has
      considerable costs. As pet ownership increases in some developing countries,
      especially China, and trends continue in pet food toward higher content and
      quality of meat, globally, pet ownership will compound the environmental impacts
      of human dietary choices. Reducing the rate of dog and cat ownership, perhaps in
      favor of other pets that offer similar health and emotional benefits would
      considerably reduce these impacts. Simultaneous industry-wide efforts to reduce
      overfeeding, reduce waste, and find alternative sources of protein will also
      reduce these impacts.

PMID- 28767701
TI  - Cardiac-directed expression of a catalytically inactive adenylyl cyclase 6
      protects the heart from sustained beta-adrenergic stimulation.
AB  - OBJECTIVES: Increased expression of adenylyl cyclase type 6 (AC6) has beneficial
      effects on the heart through cyclic adenosine monophosphate (cAMP)-dependent and
      cAMP-independent pathways. We previously generated a catalytically inactive
      mutant of AC6 (AC6mut) that has an attenuated response to beta-adrenergic
      receptor stimulation, and, consequently, exhibits reduced myocardial cAMP
      generation. In the current study we test the hypothesis that cardiac-directed
      expression of AC6mut would protect the heart from sustained beta-adrenergic
      receptor stimulation, a condition frequently encountered in patients with heart
      failure. METHODS AND RESULTS: AC6mut mice and transgene negative siblings
      received osmotic mini-pumps to provide continuous isoproterenol infusion for
      seven days. Isoproterenol infusion caused deleterious effects that were
      attenuated by cardiac-directed AC6mut expression. Both groups showed reduced left
      ventricular (LV) ejection fraction, but the reduction was less in AC6mut mice (p
      = 0.047). In addition, AC6mut mice showed superior left ventricular function,
      manifested by higher values for LV peak +dP/dt (p = 0.03), LV peak -dP/dt (p =
      0.008), end-systolic pressure-volume relationship (p = 0.003) and cardiac output
      (p<0.03). LV samples of AC6mut mice had more sarco/endoplasmic reticulum Ca2+
      ATPase (SERCA2a) protein (p<0.01), which likely contributed to better LV
      function. AC6mut mice had lower rates of cardiac myocyte apoptosis (p = 0.016),
      reduced caspase 3/7 activity (p = 0.012) and increased B-cell lymphoma 2 (Bcl2)
      expression (p = 0.0001). CONCLUSION: Mice with cardiac-directed AC6mut expression
      weathered the deleterious effects of continuous isoproterenol infusion better
      than control mice, indicating cardiac protection.

PMID- 28767702
TI  - Astragaloside IV ameliorates diabetic nephropathy by modulating the mitochondrial
      quality control network.
AB  - The aim of this study was to investigate the effect and possible mechanism of
      Astragaloside IV (AS-IV) on retarding the progression of diabetic nephropathy
      (DN) in a type 2 diabetic animal model, db/db mice. Eight-week-old male db/db
      diabetic mice and their nondiabetic littermate control db/m mice were used in the
      present study. AS-IV was administered to the db/db mice by adding it to standard
      feed at a dose of 1g/kg for 12 weeks. Renal injury was assessed by urinary
      albumin excretion (UAE) and Periodic acid-Schiff staining. The protein expression
      levels of mitochondrial quality-control-associated proteins were evaluated using
      Western blotting and immunohistochemical staining analysis. At the end of the
      experiment, db/db mice showed overt renal injury, as evidenced by increased UAE,
      increased urinary N-acetyl-beta-D-glucosaminidase (NAG), expansion of mesangial
      matrix, and increased renal tubular area. AS-IV administration significantly
      reduced UAE and urinary NAG and ameliorated the renal pathologic injury seen in
      db/db mice. Furthermore, the expression of dynamin-related protein 1 (Drp-1),
      mitochondrial fission protein 1 (Fis-1), and mitochondrial fission factor (MFF),
      the main regulators of mitochondrial fission, was significantly increased in
      db/db mice. Moreover, PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated
      mitophagy was abnormally activated in db/db mice. AS-IV significantly reduced
      renal Drp-1, Fis-1, and MFF expression and downregulated PINK1/Parkin-mediated
      mitophagy in db/db mice. However, mitochondrial biogenesis and mitochondrial
      fusion-associated protein levels were not significantly different between db/m
      and db/db mice in our study, with or without AS-IV treatment. In conclusion,
      administration of AS-IV could retard DN progression in type 2 diabetes mice,
      which might be associated with restoration of the mitochondrial quality control
      network.

PMID- 28767703
TI  - Simulated space radiation sensitizes bone but not muscle to the catabolic effects
      of mechanical unloading.
AB  - Deep space travel exposes astronauts to extended periods of space radiation and
      mechanical unloading, both of which may induce significant muscle and bone loss.
      Astronauts are exposed to space radiation from solar particle events (SPE) and
      background radiation referred to as galactic cosmic radiation (GCR). To explore
      interactions between skeletal muscle and bone under these conditions, we
      hypothesized that decreased mechanical load, as in the microgravity of space,
      would lead to increased susceptibility to space radiation-induced bone and muscle
      loss. We evaluated changes in bone and muscle of mice exposed to hind limb
      suspension (HLS) unloading alone or in addition to proton and high (H) atomic
      number (Z) and energy (E) (HZE) (16O) radiation. Adult male C57Bl/6J mice were
      randomly assigned to six groups: No radiation +/- HLS, 50 cGy proton radiation +/
      HLS, and 50 cGy proton radiation + 10 cGy 16O radiation +/- HLS. Radiation alone
      did not induce bone or muscle loss, whereas HLS alone resulted in both bone and
      muscle loss. Absolute trabecular and cortical bone volume fraction (BV/TV) was
      decreased 24% and 6% in HLS-no radiation vs the normally loaded no-radiation
      group. Trabecular thickness and mineral density also decreased with HLS. For some
      outcomes, such as BV/TV, trabecular number and tissue mineral density, additional
      bone loss was observed in the HLS+proton+HZE radiation group compared to HLS
      alone. In contrast, whereas HLS alone decreased muscle mass (19% gastrocnemius,
      35% quadriceps), protein synthesis, and increased proteasome activity, radiation
      did not exacerbate these catabolic outcomes. Our results suggest that combining
      simulated space radiation with HLS results in additional bone loss that may not
      be experienced by muscle.

PMID- 28767704
TI  - B. abortus RNA is the component involved in the down-modulation of MHC-I
      expression on human monocytes via TLR8 and the EGFR pathway.
AB  - Despite eliciting a potent CD8+ T cell response, Brucella abortus is able to
      persist and establish a chronic infection inside its host. We have previously
      reported that the infection of human monocytes/macrophages with B. abortus
      inhibits the IFN-gamma-induced MHC-I cell surface expression down-modulating
      cytotoxic CD8+ T cell responses. MHC-I down-modulation depends on bacterial
      viability and results from the capacity of B. abortus to retain the MHC-I
      molecules within the Golgi apparatus. Furthermore, we recently demonstrated that
      epidermal growth factor receptor (EGFR) pathway is involved in this phenomenon
      and that this is an early event during infection. However, the components and
      mechanisms whereby B. abortus is able to down-modulate MHC-I remained to be
      elucidated. In this study we demonstrated that the down-modulation of MHC-I
      expression is not mediated by well-known Brucella virulence factors but instead
      by B. abortus RNA, a PAMP associated to viability (vita-PAMP). Surprisingly,
      completely degraded RNA was also able to inhibit MHC-I expression to the same
      extent as intact RNA. Accordingly, B. abortus RNA and its degradation products
      were able to mimic the MHC-I intracellular retention within the Golgi apparatus
      observed upon infection. We further demonstrated that TLR8, a single-stranded RNA
      and RNA degradation products sensor, was involved in MHC-I inhibition. On the
      other hand, neutralization of the EGFR reversed the MHC-I inhibition, suggesting
      a connection between the TLR8 and EGFR pathways. Finally, B. abortus RNA-treated
      macrophages display diminished capacity of antigen presentation to CD8+ T cells.
      Overall, our results indicate that the vita-PAMP RNA as well as its degradation
      products constitute novel virulence factors whereby B. abortus, by a TLR8
      dependent mechanism and through the EGFR pathway, inhibits the IFN-gamma-induced
      MHC-I surface expression on human monocytes/macrophages. Thus, bacteria can hide
      within infected cells and avoid the immunological surveillance of cytotoxic CD8+
      T cells.

PMID- 28767706
TI  - Correction: Under threat by popular vote: German-speaking immigrants' affect and
      cognitions following the Swiss vote against mass immigration.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0175896.].

PMID- 28767705
TI  - Changes in chromosome territory position within the nucleus reflect alternations
      in gene expression related to embryonic lineage specification.
AB  - Loss of totipotentcy in an early embryo is directed by molecular processes
      responsible for cell fate decisions. Three dimensional genome organisation is an
      important factor linking chromatin architecture with stage specific gene
      expression patterns. Little is known about the role of chromosome organisation in
      gene expression regulation of lineage specific factors in mammalian embryos.
      Using bovine embryos as a model we have described these interactions at key
      developmental stages. Three bovine chromosomes (BTA) that differ in size, number
      of carried genes, and contain loci for key lineage regulators OCT4, NANOG and
      CDX2, were investigated. The results suggest that large chromosomes regardless of
      their gene density (BTA12 gene-poor, BTA5 gene-rich) do not significantly change
      their radial position within the nucleus. Gene loci however, may change its
      position within the chromosome territory (CT) and relocate its periphery, when
      stage specific process of gene activation is required. Trophectoderm specific
      CDX2 and epiblast precursor NANOG loci tend to locate on the surface or outside
      of the CTs, at stages related with their high expression. We postulate that the
      observed changes in CT shape reflect global alternations in gene expression
      related to differentiation.

PMID- 28767707
TI  - Murine gammaherpesvirus M2 antigen modulates splenic B cell activation and
      terminal differentiation in vivo.
AB  - Murine gammaherpesvirus 68 (MHV68) infection of laboratory strains of mice has
      provided a tractable small animal model for dissecting gammaherpesvirus
      pathogenesis. The MHV68 latency associated antigen M2 promotes viral latency
      establishment in germinal center (GC) B cells and plays an important role in
      virus infection of plasma cells (PCs), which is linked to virus reactivation.
      More recently, M2 has been highlighted as a potent immunomodulatory molecule
      capable of hindering both cell-mediated and humoral immunity to MHV68 infection
      and subsequent challenges. M2 expression in B cells results in activation of B
      cell receptor signaling pathways that promote proliferation, differentiation, and
      cytokine production-a hallmark of gammaherpesviruses. In this study, we utilized
      an adoptive transfer model to explore the biological consequence of M2 expression
      in activated B cells in vivo. Secondly, we engineered and validated two
      independent MHV68 M2 reporter viruses that track M2 protein expression in
      latently infected B cells during infection. Here we demonstrate that upon
      adoptive transfer into naive mice, M2 expression promotes activated primary B
      cells to competitively establish residency in the spleen as either a GC B cell or
      a PC, most notably in the absence of an ongoing GC reaction. Moreover, M2 antigen
      drives robust PC differentiation and IL10 production in vivo in the absence of
      other viral factors. Lastly, we confirm that M2 expression during MHV68 infection
      is localized to the GC compartment, which is a long term latency reservoir for
      gammaherpesviruses. Overall, these observations are consistent with, and extend
      upon previous reports of M2 function in B cells and within the context of MHV68
      infection. Moreover, this work provides support for a model by which M2-driven
      dysregulation of B cell function compromises multiple aspects of antiviral
      immunity to achieve persistence within the infected host.

PMID- 28767709
TI  - Improved biogas production and biodegradation of oilseed rape straw by using
      kitchen waste and duck droppings as co-substrates in two-phase anaerobic
      digestion.
AB  - Oilseed rape straw (ORS) is a kind of biorefractory waste widely existing in the
      rural area of China, which is highly suitable to mix with kitchen waste (KW) and
      duck droppings (DD) in two-phase anaerobic digestion (AD). This research
      introduced the importance of KW and DD addition to improve the biogas production
      and biodegradation of ORS. A set of comparative experiments were conducted on two
      phase mono- and co-digestion with organic load of 60 g VS/L. The total methane
      yield (TMY) and the biodegradation of ORS of co-digestions were obviously
      improving, and the synergistic effect found in the two-phase co-digestions. The
      optimum mixing ratio of ORS, KW and DD was 50:40:10, and the corresponding TMY
      and VS degradation rate of ORS were 374.5 mL/g VS and 49.7%, respectively.
      Addition of KW and DD maintained the pH within the optimal range for the
      hydrolyzing-acidification, improved the phase separation and buffering capacity
      of AD system.

PMID- 28767710
TI  - Correction: A scoring system to effectively evaluate central nervous system
      tuberculosis in patients with miliary tuberculosis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0176651.].

PMID- 28767708
TI  - Physiological stress and Hendra virus in flying-foxes (Pteropus spp.), Australia.
AB  - Pteropid bats (flying-foxes) are the natural reservoir of Hendra virus, an
      emergent paramyxovirus responsible for fatal infection in horses and humans in
      Australia. Pteropus alecto (the Black flying-fox) and the paraphyletic P.
      conspicillatus (the Spectacled flying-fox) appear to be the primary reservoir
      hosts. Previous studies have suggested that physiological and ecological factors
      may underpin infection dynamics in flying-foxes, and subsequent spillover to
      horses and in turn humans. We sought to examine temporal trends in urinary
      cortisol concentration in wild Australian flying-fox populations, to elucidate
      the putative relationship between Hendra virus infection and physiological
      stress. Pooled and individual urine samples were non-invasively collected from
      under roosting flying-foxes at two latitudinally disparate regions in the eastern
      Australian state of Queensland. Hendra virus detection, and (in individual urine
      samples) sex and species determination were PCR-based. Urinary cortisol
      measurement used a validated enzyme immunoassay. We found no direct correlation
      between increased urinary cortisol and Hendra virus excretion, but our findings
      do suggest a biologically plausible association between low winter temperatures
      and elevated cortisol levels in P. alecto in the lower latitude Southeast
      Queensland roosts. We hypothesize an indirect association between low winter
      temperatures and increased Hendra virus infection and excretion, mediated by the
      physiological cost of thermoregulation. Our findings and our approach are
      directly relevant to elaboration of the disease ecology of Nipah virus and other
      emerging henipaviruses in bats. More broadly, they inform investigation of
      emerging disease infection dynamics across the wildlife/livestock/human
      interface.

PMID- 28767711
TI  - Progress towards a public chemogenomic set for protein kinases and a call for
      contributions.
AB  - Protein kinases are highly tractable targets for drug discovery. However, the
      biological function and therapeutic potential of the majority of the 500+ human
      protein kinases remains unknown. We have developed physical and virtual
      collections of small molecule inhibitors, which we call chemogenomic sets, that
      are designed to inhibit the catalytic function of almost half the human protein
      kinases. In this manuscript we share our progress towards generation of a
      comprehensive kinase chemogenomic set (KCGS), release kinome profiling data of a
      large inhibitor set (Published Kinase Inhibitor Set 2 (PKIS2)), and outline a
      process through which the community can openly collaborate to create a KCGS that
      probes the full complement of human protein kinases.

PMID- 28767712
TI  - Changes in lipid membranes may trigger amyloid toxicity in Alzheimer's disease.
AB  - Amyloid-beta peptides (Abeta), implicated in Alzheimer's disease (AD), interact
      with the cellular membrane and induce amyloid toxicity. The composition of
      cellular membranes changes in aging and AD. We designed multi-component lipid
      models to mimic healthy and diseased states of the neuronal membrane. Using
      atomic force microscopy (AFM), Kelvin probe force microscopy (KPFM) and black
      lipid membrane (BLM) techniques, we demonstrated that these model membranes
      differ in their nanoscale structure and physical properties, and interact
      differently with Abeta1-42. Based on our data, we propose a new hypothesis that
      changes in lipid membrane due to aging and AD may trigger amyloid toxicity
      through electrostatic mechanisms, similar to the accepted mechanism of
      antimicrobial peptide action. Understanding the role of the membrane changes as a
      key activating amyloid toxicity may aid in the development of a new avenue for
      the prevention and treatment of AD.

PMID- 28767713
TI  - Apolipoprotein A-I exchange is impaired in metabolic syndrome patients
      asymptomatic for diabetes and cardiovascular disease.
AB  - OBJECTIVE: We tested the hypothesis that HDL-apolipoprotein A-I exchange (HAE), a
      measure of high-density lipoprotein (HDL) function and a key step in reverse
      cholesterol transport (RCT), is impaired in metabolic syndrome (MetSyn) patients
      who are asymptomatic for diabetes and cardiovascular disease. We also compared
      HAE with cell-based cholesterol efflux capacity (CEC) to address previous reports
      that CEC is enhanced in MetSyn populations. METHODS: HAE and ABCA1-specific CEC
      were measured as tests of HDL function in 60 MetSyn patients and 14
      normolipidemic control subjects. Predictors of HAE and CEC were evaluated with
      multiple linear regression modeling using clinical markers of MetSyn and CVD
      risk. RESULTS: HAE was significantly reduced in MetSyn patients (49.0 +/- 10.9%
      vs. 61.2 +/- 6.1%, P < 0.0001), as was ABCA1-specific CEC (10.1 +/- 1.6% vs. 12.3
      +/- 2.0%, P < 0.002). Multiple linear regression analysis identified apoA-I
      concentration as a significant positive predictor of HAE, and MetSyn patients had
      significantly lower HAE per mg/dL of apoA-I (P = 0.004). MetSyn status was a
      negative predictor of CEC, but triglyceride (TG) was a positive predictor of CEC,
      with MetSyn patients having higher CEC per mg/dL of TG, but lower overall CEC
      compared to controls. CONCLUSIONS: MetSyn patients have impaired HAE that
      contributes to reduced capacity for ABCA1-mediated CEC. MetSyn status is
      inversely correlated with CEC but positively correlated with TG, which explains
      the contradictory results from earlier MetSyn studies focused on CEC. HAE and CEC
      are inhibited in MetSyn patients over a broad range of absolute apoA-I and HDL
      particle levels, supporting the observation that this patient population bears
      significant residual cardiovascular disease risk.

PMID- 28767714
TI  - HIV-associated mortality in the era of antiretroviral therapy scale-up - Nairobi,
      Kenya, 2015.
AB  - BACKGROUND: Declines in HIV prevalence and increases in antiretroviral treatment
      coverage have been documented in Kenya, but population-level mortality associated
      with HIV has not been directly measured. In urban areas where a majority of
      deaths pass through mortuaries, mortuary-based studies have the potential to
      contribute to our understanding of excess mortality among HIV-infected persons.
      We used results from a cross-sectional mortuary-based HIV surveillance study to
      estimate the association between HIV and mortality for Nairobi, the capital city
      of Kenya. METHODS AND FINDINGS: HIV seropositivity in cadavers measured at the
      two largest mortuaries in Nairobi was used to estimate HIV prevalence in adult
      deaths. Model-based estimates of the HIV-infected and uninfected population for
      Nairobi were used to calculate a standardized mortality ratio and population
      attributable fraction for mortality among the infected versus uninfected
      population. Monte Carlo simulation was used to assess sensitivity to
      epidemiological assumptions. When standardized to the age and sex distribution of
      expected deaths, the estimated HIV positivity among adult deaths aged 15 years
      and above in Nairobi was 20.9% (95% CI 17.7-24.6%). The standardized mortality
      ratio of deaths among HIV-infected versus uninfected adults was 4.35 (95% CI 3.67
      5.15), while the risk difference was 0.016 (95% CI 0.013-0.019). The HIV
      population attributable mortality fraction was 0.161 (95% CI 0.131-0.190).
      Sensitivity analyses demonstrated robustness of results. CONCLUSIONS: Although
      73.6% of adult PLHIV receive antiretrovirals in Nairobi, their risk of death is
      four-fold greater than in the uninfected, while 16.1% of all adult deaths in the
      city can be attributed to HIV infection. In order to further reduce HIV
      associated mortality, high-burden countries may need to reach very high levels of
      diagnosis, treatment coverage, retention in care, and viral suppression.

PMID- 28767715
TI  - Lafora disease in miniature Wirehaired Dachshunds.
AB  - Lafora disease (LD) is an autosomal recessive late onset, progressive myoclonic
      epilepsy with a high prevalence in the miniature Wirehaired Dachshund. The
      disease is due to a mutation in the Epm2b gene which results in intracellular
      accumulation of abnormal glycogen (Lafora bodies). Recent breed-wide testing
      suggests that the carrier plus affected rate may be as high as 20%. A
      characteristic feature of the disease is spontaneous and reflex myoclonus;
      however clinical signs and disease progression are not well described. A survey
      was submitted to owners of MWHD which were homozygous for Epm2b mutation (breed
      club testing program) or had late onset reflex myoclonus and clinical diagnosis
      of LD. There were 27 dogs (11 male; 16 female) for analysis after young mutation
      positive dogs that had yet to develop disease were excluded. Average age of onset
      of clinical signs was 6.94 years (3.5-12). The most common initial presenting
      sign was reflex and spontaneous myoclonus (77.8%). Other presenting signs
      included hypnic myoclonus (51.9%) and generalized seizures (40.7%). Less common
      presenting signs include focal seizures, "jaw smacking", "fly catching", "panic
      attacks", impaired vision, aggression and urinary incontinence. All these
      clinical signs may appear, and then increase in frequency and intensity over
      time. The myoclonus in particular becomes more severe and more refractory to
      treatment. Signs that developed later in the disease include dementia (51.9%),
      blindness (48.1%), aggression to people (25.9%) and dogs (33.3%), deafness
      (29.6%) and fecal (29.6%) and urinary (37.0%) incontinence as a result of loss of
      house training (disinhibited type behavior). Further prospective study is needed
      to further characterize the canine disease and to allow more specific therapeutic
      strategies and to tailor therapy as the disease progresses.

PMID- 28767716
TI  - Factors associated with interest in novel interfaces for upper limb prosthesis
      control.
AB  - BACKGROUND: Surgically invasive interfaces for upper limb prosthesis control may
      allow users to operate advanced, multi-articulated devices. Given the potential
      medical risks of these invasive interfaces, it is important to understand what
      factors influence an individual's decision to try one. METHODS: We conducted an
      anonymous online survey of individuals with upper limb loss. A total of 232
      participants provided personal information (such as age, amputation level, etc.)
      and rated how likely they would be to try noninvasive (myoelectric) and invasive
      (targeted muscle reinnervation, peripheral nerve interfaces, cortical interfaces)
      interfaces for prosthesis control. Bivariate relationships between interest in
      each interface and 16 personal descriptors were examined. Significant variables
      from the bivariate analyses were then entered into multiple logistic regression
      models to predict interest in each interface. RESULTS: While many of the
      bivariate relationships were significant, only a few variables remained
      significant in the regression models. The regression models showed that
      participants were more likely to be interested in all interfaces if they had
      unilateral limb loss (p <= 0.001, odds ratio >= 2.799). Participants were more
      likely to be interested in the three invasive interfaces if they were younger (p
      < 0.001, odds ratio <= 0.959) and had acquired limb loss (p <= 0.012, odds ratio
      >= 3.287). Participants who used a myoelectric device were more likely to be
      interested in myoelectric control than those who did not (p = 0.003, odds ratio =
      24.958). CONCLUSIONS: Novel prosthesis control interfaces may be accepted most
      readily by individuals who are young, have unilateral limb loss, and/or have
      acquired limb loss However, this analysis did not include all possible factors
      that may have influenced participant's opinions on the interfaces, so additional
      exploration is warranted.

PMID- 28767717
TI  - Disentangling the influence of environmental and anthropogenic factors on the
      distribution of endemic vascular plants in Sardinia.
AB  - Due to the impelling urgency of plant conservation and the increasing
      availability of high resolution spatially interpolated (e.g. climate variables)
      and categorical data (e.g. land cover and vegetation type), many recent studies
      have examined relationships among plant species distributions and a diversified
      set of explanatory factors; nevertheless, global and regional patterns of endemic
      plant richness remain in many cases unexplained. One such pattern is the 294
      endemic vascular plant taxa recorded on a 1 km resolution grid on the
      environmentally heterogeneous island of Sardinia. Sixteen predictors, including
      topographic, geological, climatic and anthropogenic factors, were used to model
      local (number of taxa inside each 1 km grid cell) Endemic Vascular Plant Richness
      (EVPR). Generalized Linear Models were used to evaluate how each factor affected
      the distribution of local EVPR. Significant relationships with local EVPR and
      topographic, geological, climatic and anthropogenic factors were found. In
      particular, elevation explained the larger fraction of variation in endemic
      richness but other environmental factors (e.g. precipitation seasonality and
      slope) and human-related factors (e.g. the Human Influence Index (HII) and the
      proportion of anthropogenic land uses) were, respectively, positively and
      negatively correlated with local EVPR. Regional EVPR (number of endemic taxa
      inside each 100 m elevation interval) was also measured to compare local and
      regional EVPR patterns along the elevation gradient. In contrast to local,
      regional EVPR tended to decrease with altitude partly due to the decreasing area
      covered along altitude. The contrasting results between local and regional
      patterns suggest that local richness increases as a result of increased
      interspecific aggregation along altitude, whereas regional richness may depend on
      the interaction between area and altitude. This suggests that the shape and
      magnitude of the species-area relationship might vary with elevation. This work
      provides-for the first time in Sardinia-a comprehensive analysis of the influence
      of environmental factors on the pattern of EVPR in the entire territory, from sea
      level to the highest peaks. Elevation, as well as other environmental and human
      related variables, were confirmed to be influencing factors. In addition,
      variations of EVPR patterns at regional-to-local spatial scales inspire next
      investigations on the possible interaction between elevation and area in
      explaining patterns of plant species richness.

PMID- 28767719
TI  - Task-shifting impact of introducing a pilot community health worker cadre into
      Zambia's public sector health workforce.
AB  - BACKGROUND: The Zambia Ministry of Health (MOH) recruited and trained a new cadre
      of Community Health Assistants (CHAs) as part of its National Community Health
      Strategy. The inaugural class of 307 CHAs completed one year of training in July
      2012 and deployed to their communities. METHODS: The impact of the CHA program on
      the volume and type of health services provided at health posts and their
      respective referral health centers was measured with a non-randomized difference
      in-differences design. Monthly health service provision data was collected for 12
      months before and after CHA deployment at 8 health posts along with 8 referral
      health centers. The analysis controlled for seasonality, changes in non-CHA
      staffing, and periodic regional child health campaigns, and used facility-level
      fixed effects. RESULTS: Deploying two CHAs to a health post did not lead to a
      statistically-discernible increase in services at the intervention facilities.
      Health services provided at referral health centers increased by 697.9 services
      per month (95% CI: 131.4 to 1,264.3, p = .016), and combined services (at health
      posts and referral health centers) increased by 848.6 services per month (95% CI:
      178.2 to 1,519.1, p = .013). CONCLUSION: In this pilot, the addition of CHAs in
      rural areas increased health service provision at referral health facilities and
      at facilities overall, shifting the burden of basic health services away from
      more highly trained health workers. Shifting tasks to lesser-trained, less
      expensive cadres like the CHAs, policymakers can rapidly improve access to care
      with constrained budgets. Evaluations measuring the direct impact of lower level
      cadres without accounting for task-shifting may underestimate their contribution
      to the health workforce.

PMID- 28767718
TI  - Zygotic vinculin is not essential for embryonic development in zebrafish.
AB  - The formation of multicellular tissues during development is governed by
      mechanical forces that drive cell shape and tissue architecture. Protein
      complexes at sites of adhesion to the extracellular matrix (ECM) and cell
      neighbors, not only transmit these mechanical forces, but also allow cells to
      respond to changes in force by inducing biochemical feedback pathways. Such force
      induced signaling processes are termed mechanotransduction. Vinculin is a central
      protein in mechanotransduction that in both integrin-mediated cell-ECM and
      cadherin-mediated cell-cell adhesions mediates force-induced cytoskeletal
      remodeling and adhesion strengthening. Vinculin was found to be important for the
      integrity and remodeling of epithelial tissues in cell culture models and could
      therefore be expected to be of broad importance in epithelial morphogenesis in
      vivo. Besides a function in mouse heart development, however, the importance of
      vinculin in morphogenesis of other vertebrate tissues has remained unclear. To
      investigate this further, we knocked out vinculin functioning in zebrafish, which
      contain two fully functional isoforms designated as vinculin A and vinculin B
      that both show high sequence conservation with higher vertebrates. Using TALEN
      and CRISPR-Cas gene editing technology we generated vinculin-deficient zebrafish.
      While single vinculin A mutants are viable and able to reproduce, additional loss
      of zygotic vinculin B was lethal after embryonic stages. Remarkably, vinculin
      deficient embryos do not show major developmental defects, apart from mild
      pericardial edemas. These results lead to the conclusion that vinculin is not of
      broad importance for the development and morphogenesis of zebrafish tissues.

PMID- 28767720
TI  - Neuronal oscillations reveal the processes underlying intentional compared to
      incidental learning in children and young adults.
AB  - This EEG study investigated the neuronal processes during intentional compared to
      incidental learning in young adults and two groups of children aged 10 and 7
      years. Theta (3-8 Hz) and alpha (10-16 Hz) neuronal oscillations were analyzed to
      compare encoding processes during an intentional and an incidental encoding task.
      In all three age groups, both encoding conditions were associated with an
      increase in event-related theta activity. Encoding-related alpha suppression
      increased with age. Memory performance was higher in the intentional compared to
      the incidental task in all age groups. Furthermore, intentional learning was
      associated with an improved encoding of perceptual features, which were relevant
      for the retrieval phase. Theta activity increased from incidental to intentional
      encoding. Specifically, frontal theta increased in all age groups, while parietal
      theta increased only in adults and older children. In younger children, parietal
      theta was similarly high in both encoding phases. While alpha suppression may
      reflect semantic processes during encoding, increased theta activity during
      intentional encoding may indicate perceptual binding processes, in accordance
      with the demands of the encoding task. Higher encoding-related alpha suppression
      in the older age groups, together with age differences in parietal theta activity
      during incidental learning in young children, is in line with recent theoretical
      accounts, emphasizing the role of perceptual processes in mnemonic processing in
      young children, whereas semantic encoding processes continue to mature throughout
      middle childhood.

PMID- 28767721
TI  - Development and clinical testing of individual immunoassays for the
      quantification of serum glycoproteins to diagnose prostate cancer.
AB  - Prostate Cancer (PCa) diagnosis is currently hampered by the high false-positive
      rate of PSA evaluations, which consequently may lead to overtreatment. Non
      invasive methods with increased specificity and sensitivity are needed to improve
      diagnosis of significant PCa. We developed and technically validated four
      individual immunoassays for cathepsin D (CTSD), intercellular adhesion molecule 1
      (ICAM1), olfactomedin 4 (OLFM4), and thrombospondin 1 (THBS1). These
      glycoproteins, previously identified by mass spectrometry using a Pten mouse
      model, were measured in clinical serum samples for testing the capability of
      discriminating PCa positive and negative samples. The development yielded 4
      individual immunoassays with inter and intra-variability (CV) <15% and linearity
      on dilution of the analytes. In serum, ex vivo protein stability (<15% loss of
      analyte) was achieved for a duration of at least 24 hours at room temperature and
      2 days at 4 degrees C. The measurement of 359 serum samples from PCa positive (n
      = 167) and negative (n = 192) patients with elevated PSA (2-10 ng/ml) revealed a
      significantly improved accuracy (P <0.001) when two of the glycoproteins (CTSD
      and THBS1) were combined with %fPSA and age (AUC = 0.8109; P <0.0001; 95% CI =
      0.7673-0.8545). Conclusively, the use of CTSD and THBS1 together with commonly
      used parameters for PCa diagnosis such as %fPSA and age has the potential to
      improve the diagnosis of PCa.

PMID- 28767722
TI  - Cost-effectiveness analysis of population-based tobacco control strategies in the
      prevention of cardiovascular diseases in Tanzania.
AB  - BACKGROUND: Tobacco consumption contributes significantly to the global burden of
      disease. The prevalence of smoking is estimated to be increasing in many low
      income countries, including Tanzania, especially among women and youth. Even so,
      the implementation of tobacco control measures has been discouraging in the
      country. Efforts to foster investment in tobacco control are hindered by lack of
      evidence on what works and at what cost. AIMS: We aim to estimate the cost and
      cost-effectiveness of population-based tobacco control strategies in the
      prevention of cardiovascular diseases (CVD) in Tanzania. MATERIALS AND METHODS: A
      cost-effectiveness analysis was performed using an Excel-based Markov model, from
      a governmental perspective. We employed an ingredient approach and step-down
      methodologies in the costing exercise following a government perspective.
      Epidemiological data and efficacy inputs were derived from the literature. We
      used disability-adjusted life years (DALYs) averted as the outcome measure. A
      probabilistic sensitivity analysis was carried out with Ersatz to incorporate
      uncertainties in the model parameters. RESULTS: Our model results showed that all
      five tobacco control strategies were very cost-effective since they fell below
      the ceiling ratio of one GDP per capita suggested by the WHO. Increase in tobacco
      taxes was the most cost-effective strategy, while a workplace smoking ban was the
      least cost-effective option, with a cost-effectiveness ratio of US$5 and US$267,
      respectively. CONCLUSIONS: Even though all five interventions are deemed very
      cost-effective in the prevention of CVD in Tanzania, more research on budget
      impact analysis is required to further assess the government's ability to
      implement these interventions.

PMID- 28767723
TI  - Improving rice population productivity by reducing nitrogen rate and increasing
      plant density.
AB  - In terms of tillering potential, the aboveground portions of rice are
      significantly influenced by the nitrogen level (NL) and transplant density (TD).
      To obtain a suitable combination of NL and TD, five NLs (0, 90, 180, 270 and 360
      kg ha-1) and two TDs [high density (HD), 32.5*104 hills ha-1; low density (LD),
      25.5*104 hills ha-1] were used in the rice experiments during 2012 to 2014, in
      Jiangsu, China. The results showed the highest grain yield of rice obtained at HD
      and LD when N supply was 180 and 270 kg ha-1, respectively. That's because there
      are more tillers per unit area, a larger leaf biomass fraction of total
      aboveground biomass, a larger leaf area index (LAI) and a larger canopy
      photosynthesis potential (CPP) at HD. It can be concluded that, higher rice
      planting densities resulted in less N inputs, while more N is needed to improve
      single plant actual tiller ability under low density to offset the reduced
      planting density. When the NL was more than 180 kg ha-1, the actual tillering
      ability of a single plant at LD was 20% more than that at HD. Based on these
      results, the supply of 1 kg N can be replaced by adding approximately 1000
      planting hills per hectare. Therefore, adjusting the transplant density could be
      an efficient method to reduce the amount of nitrogen fertilizer and increase the
      nitrogen fertilizer use efficiency, which is very conducive to the sustainable
      development of agriculture.

PMID- 28767724
TI  - beta3 integrin expression is required for invadopodia-mediated ECM degradation in
      lung carcinoma cells.
AB  - Cancer related deaths are primarily due to tumor metastasis. To facilitate their
      dissemination to distant sites, cancer cells develop invadopodia, actin-rich
      protrusions capable of degrading the surrounding extracellular matrix (ECM). We
      aimed to determine whether beta3 integrin participates in invadopodia formed by
      lung carcinoma cells, based on our previous findings of specific TGF-beta
      induction of beta3 integrin dependent metastasis in animal models of lung
      carcinoma. In this study, we demonstrate that lung carcinoma cells form
      invadopodia in response to TGF-beta exposure. Invadopodia formation and
      degradation activity is dependent on beta3 integrin expression since beta3
      integrin deficient cells are not able to degrade gelatin-coated surfaces. Even
      more, transient over-expression of SRC did not restore invadopodia formation in
      beta3 integrin deficient cells. Finally, we observed that blockade of PLC
      dependent signaling leads to more intense labeling for beta3 integrin in
      invadopodia. Our results suggest that beta3 integrin function, and location, in
      lung cancer cells are essential for invadopodia formation, and this integrin
      regulates the activation of different signal pathways necessary for the invasive
      structure. beta3 integrin has been associated with poor prognosis and increased
      metastasis in several carcinoma types, including lung cancer. Our findings
      provide new evidence to support the use of targeted therapies against this
      integrin to combat the onset of metastases.

PMID- 28767725
TI  - DNA mutation motifs in the genes associated with inherited diseases.
AB  - Mutations in human genes can be responsible for inherited genetic disorders and
      cancer. Mutations can arise due to environmental factors or spontaneously. It has
      been shown that certain DNA sequences are more prone to mutate. These sites are
      termed hotspots and exhibit a higher mutation frequency than expected by chance.
      In contrast, DNA sequences with lower mutation frequencies than expected by
      chance are termed coldspots. Mutation hotspots are usually derived from a
      mutation spectrum, which reflects particular population where an effect of a
      common ancestor plays a role. To detect coldspots/hotspots unaffected by
      population bias, we analysed the presence of germline mutations obtained from
      HGMD database in the 5-nucleotide segments repeatedly occurring in genes
      associated with common inherited disorders, in particular, the PAH, LDLR, CFTR,
      F8, and F9 genes. Statistically significant sequences (mutational motifs) rarely
      associated with mutations (coldspots) and frequently associated with mutations
      (hotspots) exhibited characteristic sequence patterns, e.g. coldspots contained
      purine tract while hotspots showed alternating purine-pyrimidine bases, often
      with the presence of CpG dinucleotide. Using molecular dynamics simulations and
      free energy calculations, we analysed the global bending properties of two
      selected coldspots and two hotspots with a G/T mismatch. We observed that the
      coldspots were inherently more flexible than the hotspots. We assume that this
      property might be critical for effective mismatch repair as DNA with a mutation
      recognized by MutSalpha protein is noticeably bent.

PMID- 28767727
TI  - Rock climbing alters plant species composition, cover, and richness in
      Mediterranean limestone cliffs.
AB  - Rock climbing is among the outdoor activities that have undergone the highest
      growth since the second half of the 20th century. As a result, cliff habitats,
      historically one of the least disturbed by human colonization worldwide, are
      facing more intense human pressure than ever before. However, there is little
      data on the impact of this activity in plant-communities, and such information is
      indispensable for adequate manager decision-making. The goal of this study was to
      determine the impact of rock climbing on plant communities in terms of cover,
      richness, and composition in relation to climbing intensity on typical
      Mediterranean limestone cliffs. Three rock-climbing sites were selected in the
      Baetic range (SE Spain), corresponding to qualitative categories of climbing
      frequentation: i)"low" (low frequentation with intermittent climbing),
      ii)"medium" (high frequentation without overcrowding), and iii) "high" (high
      frequentation with overcrowding). Within each site, we selected climbing routes
      and adjacent areas free of climbing, then we carried out a photoplot-based
      sampling by rappelling. We analysed the images to calculate: richness, species
      cover, and total cover. This study shows that rock climbing negatively affected
      the cliff plant community at all three study sites. A significant decrease in
      plant cover, species richness and a shift in the community composition were
      recorded for climbed areas, the cover being the variable most sensitive to rock
      climbing. Impact observed proved to be related to the frequentation level. Low
      frequentation sites, with usually more specialized climbers, underwent relatively
      mild damages, whereas at high frequentation sites the impact was severe and the
      conservation of the species, especially rare ones, became jeopardized. Our study
      is the first one available to investigate climbing impact on plant communities in
      Mediterranean areas, but more research on the impact of rock climbing is needed
      to assess the regulation of this activity. Regarding management guidelines, we
      propose a management guideline protocol to evaluate climbing routes and design:
      i) "Sites free of climbing", ii) "Strictly regulated climbing routes", iii)
      "Mildly regulated climbing routes", or iv) "Free climbing routes".

PMID- 28767726
TI  - High-resolution phenotyping identifies NK cell subsets that distinguish healthy
      children from adults.
AB  - Natural killer (NK) cells are critical in immune defense against infected,
      stressed or transformed cells. Their function is regulated by the heterogeneous
      expression of a wide array of surface receptors that shape its phenotypic
      diversity. Although NK cells develop in the bone marrow and secondary lymphoid
      tissues, substantive differentiation is apparent in the peripheral blood
      including known age-related variation. In order to gain greater insight into
      phenotypic and functional variation within peripheral blood NK cells across age
      groups, we used multi-parametric, polyfunctional flow cytometry to interrogate
      the NK cell variability in 20 healthy adults and 15 5-10, 11-15 and 16-20 year
      old children. We found that the normative ranges in both adults and children
      displayed great inter-individual variation for most markers. While the expression
      of several receptors did not differ, among those that did, the majority of the
      differences existed between adults and the three pediatric groups, rather than
      among children of different ages. Interestingly, we also identified variation in
      the individual expression of some markers by sex and ethnicity. Combinatorial
      analysis of NK cell receptors revealed intermediate subsets between the
      CD56bright and CD56dim NK cells. Furthermore, on examining the NK cell diversity
      by age, adults were discovered to have the lowest developmental diversity. Thus,
      our findings identify previously unappreciated NK cell subsets potentially
      distinguishing children from adults and suggest functional correlates that may
      have relevance in age-specific host defense.

PMID- 28767728
TI  - Crystal structure of Qa-1a with bound Qa-1 determinant modifier peptide.
AB  - Qa-1 is a non-classical Major Histocompatibility (MHC) class I molecule that
      generally presents hydrophobic peptides including Qdm derived from the leader
      sequence of classical MHC I molecules for immune surveillance by NK cells. Qa-1
      bound peptides derived from the TCR Vbeta8.2 of activated T cells also activates
      CD8+ regulatory T cells to control autoimmunity and maintain self-tolerance. Four
      allotypes of Qa-1 (Qa-1a-d) are expressed that are highly conserved in sequence
      but have several variations that could affect peptide binding to Qa-1 or TCR
      recognition. Here, we determined the structure of Qa-1a with bound Qdm peptide.
      While the overall structure is very similar to that of Qa-1b, there are several
      amino acid differences around the peptide binding platform that could affect TCR
      recognition. Most notably, two amino acid substitutions are found in the pocket
      P2, which binds the anchor residue Met2 of the Qdm peptide. These residues affect
      both the size and shape of the binding pocket, as well as affect the charge at
      physiologic pH, suggesting Qa-1a and Qa-1b could present slightly distinct
      peptide reservoirs, which could presumably be recognized by different populations
      of CD8+ T cells.

PMID- 28767731
TI  - Hospital Trusts productivity in the English NHS: Uncovering possible drivers of
      productivity variations.
AB  - BACKGROUND: Health care systems in OECD countries are increasingly facing
      economic challenges and funding pressures. These normally demand interventions
      (political, financial and organisational) aimed at improving the efficiency of
      the health system as a whole and its single components. In 2009, the English NHS
      Chief Executive, Sir David Nicholson, warned that a potential funding gap of L20
      billion should be met by extensive efficiency savings by March 2015. Our study
      investigates possible drivers of differential Trust performance (productivity)
      for the financial years 2010/11-2012/13. METHODS: Following accounting practice,
      we define Productivity as the ratio of Outputs over Inputs. We analyse variation
      in both Total Factor and Labour Productivity using ordinary least squares
      regressions. We explicitly included in our analysis factors of differential
      performance highlighted in the Nicholson challenge as the sources were the
      efficiency savings should come from. Explanatory variables include efficiency in
      resource use measures, Trust and patient characteristics, and quality of care.
      RESULTS: We find that larger Trusts and Foundation Trusts are associated with
      lower productivity, as are those treating a greater proportion of both older
      and/or younger patients. Surprisingly treating more patients in their last year
      of life is associated with higher Labour Productivity.

PMID- 28767730
TI  - Community context and sub-neighborhood scale detail to explain dengue,
      chikungunya and Zika patterns in Cali, Colombia.
AB  - BACKGROUND: Cali, Colombia has experienced chikungunya and Zika outbreaks and
      hypoendemic dengue. Studies have explained Cali's dengue patterns but lack the
      sub-neighborhood-scale detail investigated here. METHODS: Spatial-video
      geonarratives (SVG) with Ministry of Health officials and Community Health
      Workers were collected in hotspots, providing perspective on perceptions of why
      dengue, chikungunya and Zika hotspots exist, impediments to control, and social
      outcomes. Using spatial video and Google Street View, sub-neighborhood features
      possibly contributing to incidence were mapped to create risk surfaces, later
      compared with dengue, chikungunya and Zika case data. RESULTS: SVG captured
      insights in 24 neighborhoods. Trash and water risks in Calipso were mapped using
      SVG results. Perceived risk factors included proximity to standing water, canals,
      poverty, invasions, localized violence and military migration. These risks
      overlapped case density maps and identified areas that are suitable for
      transmission but are possibly underreporting to the surveillance system.
      CONCLUSION: Resulting risk maps with local context could be leveraged to increase
      vector-control efficiency- targeting key areas of environmental risk.

PMID- 28767729
TI  - Protective effect of clusterin on rod photoreceptor in rat model of retinitis
      pigmentosa.
AB  - Retinitis Pigmentosa (RP) begins with the death of rod photoreceptors and is
      slowly followed by a gradual loss of cones and a rearrangement of the remaining
      retinal neurons. Clusterin is a chaperone protein that protects cells and is
      involved in various pathophysiological stresses, including retinal degeneration.
      Using a well-established transgenic rat model of RP (rhodopsin S334ter), we
      investigated the effects of clusterin on rod photoreceptor survival. To
      investigate the role of clusterin in S334ter-line3 retinas, Voronoi analysis and
      immunohistochemistry were used to evaluate the geometry of rod distribution.
      Additionally, immunoblot analysis, Bax activation, STAT3 and Akt phosphorylation
      were used to evaluate the pathway involved in rod cell protection. In this study,
      clusterin (10MUg/ml) intravitreal treatment produced robust preservation of rod
      photoreceptors in S334ter-line3 retina. The mean number of rods in 1mm2 was
      significantly greater in clusterin injected RP retinas (postnatal (P) 30, P45,
      P60, & P75) than in age-matched saline injected RP retinas (P<0.01). Clusterin
      activated Akt, STAT3 and significantly reduced Bax activity; in addition to
      inducing phosphorylated STAT3 in Muller cells, which suggests it may indirectly
      acts on photoreceptors. Thus, clusterin treatment may interferes with mechanisms
      leading to rod death by suppressing cell death through activation of Akt and
      STAT3, followed by Bax suppression. Novel insights into the pathway of how
      clusterin promotes the rod cell survival suggest this treatment may be a
      potential therapeutic strategy to slow progression of vision loss in human RP.

PMID- 28767732
TI  - Influence of exposure parameters and iterative reconstruction on automatic airway
      segmentation and analysis on MDCT-An ex vivo phantom study.
AB  - OBJECTIVES: To evaluate the influence of exposure parameters and raw-data-based
      iterative reconstruction (IR) on computer-aided segmentation and quantitative
      analysis of the tracheobronchial tree on multidetector computed tomography
      (MDCT). MATERIAL AND METHODS: 10 porcine heart-lung-explants were mounted inside
      a dedicated chest phantom. MDCT was performed at 120kV and 80kV with 120, 60, 30
      and 12 mAs each. All scans were reconstructed with filtered back projection (FBP)
      or IR, resulting in a total of 160 datasets. The maximum number of detected
      airway segments, most peripheral airway generation detected, generation-specific
      airway wall thickness (WT), total diameter (TD) and normalized wall thickness
      (pi10) were compared. RESULTS: The number of detected airway segments decreased
      slightly with dose (324.8+/-118 at 120kV/120mAs vs. 288.9+/-130 at 80kV/30mAs
      with FBP, p<0.05) and was not changed by IR. The 20th generation was constantly
      detected as most peripheral. WT did not change significantly with exposure
      parameters and reconstruction algorithm across all generations: range 1st
      generation 2.4-2.7mm, 5th 1.0-1.1mm, and 10th 0.7mm with FBP; 1st 2.3-2.4mm, 5th
      1.0-1.1mm, and 10th 0.7-0.8mm with IR. pi10 was not affected as well (range 0.32
      0.34mm). CONCLUSIONS: Exposure parameters and IR had no relevant influence on
      measured airway parameters even for WT <1mm. Thus, no systematic errors would be
      expected using automatic airway analysis with low-dose MDCT and IR.

PMID- 28767733
TI  - Lactate dehydrogenase and creatine kinase as poor prognostic factors in lung
      cancer: A retrospective observational study.
AB  - PURPOSE: Circulating molecules play important roles in lung cancer diagnosis. In
      addition, plasma lactate dehydrogenase (LDH) and creatine kinase (CK) have been
      shown to be closely related to tumor progression in breast cancer, prostate
      cancer, and colonel cancer. However, the relationships between LDH and CK levels
      with metastasis occurrence and the survival status of lung cancer patients remain
      unclear. EXPERIMENTAL DESIGN: A total of 1142 lung cancer patients were enrolled
      in this study and were separated into negative or positive groups, according to
      the plasma levels of CK or LDH. Patients in both groups were assessed for
      clinical characteristics, metastasis occurrence, and survival status. The Cox
      regression model was then introduced to confirm whether CK and LDH could act as
      independent factors for predicting a poor prognosis. RESULTS: The results
      indicated that CK had a close relationship with bone (p < 0.05) and lymph node (p
      < 0.05) metastases. In addition, LDH was strongly related with bone (p < 0.05),
      adrenal gland (p < 0.05), and lymph node (p < 0.05) metastases. CK and LDH were
      also correlated with the survival status of the lung cancer patients (all p <
      0.001). According to specific histological classification analysis, it was found
      that CK was closely related to the survival status of adenocarcinoma (ADC) and
      squamous cell carcinoma (SCC) patients, while LDH was only correlated with that
      of ADC patients. Cox regression analysis confirmed that CK and LDH could act as
      independent factors for predicting a poor prognosis in ADC but not SCC patients.
      CONCLUSIONS: For the first time, our study confirmed the role of CK in metastasis
      occurrence and the survival status of lung cancer patients. In addition, it also
      demonstrated that CK and LDH could be used as independent factors to predict a
      poor prognosis in ADC patients. The identification of CK and LDH will play
      important roles in lung cancer diagnosis and poor outcome prediction in the
      future.

PMID- 28767734
TI  - Prediction of glycaemic control in young children and adolescents with type 1
      diabetes mellitus using mixed-effects logistic regression modelling.
AB  - OBJECTIVES: Glycaemic control in children and adolescents with type 1 diabetes
      mellitus can be challenging, complex and influenced by many factors. This study
      aimed to identify patient characteristics that were predictive of satisfactory
      glycaemic control in the paediatric population using a logistic regression mixed
      effects (population) modelling approach. METHODS: The data were obtained from 288
      patients aged between 1 and 22 years old recorded retrospectively over 3 years
      (1852 HbA1c observations). HbA1c status was categorised as 'satisfactory' or
      'unsatisfactory' glycaemic control, using an a priori cut-off value of HbA1c >=
      9% (75 mmol/mol), as used routinely by the hospital's endocrine paediatricians.
      Patients' characteristics were tested as covariates in the model as potential
      predictors of glycaemic control. RESULTS: There were three patient
      characteristics identified as having a significant influence on glycaemic
      control: HbA1c measurement at the beginning of the observation period (Odds Ratio
      (OR) = 0.30 per 1% HbA1c increase, 95% confidence interval (CI) = 0.20-0.41); Age
      (OR = 0.88 per year increase, 95% CI = 0.80-0.94), and fractional disease
      duration (disease duration/age, OR = 0.80 per 0.10 increase, 95% CI = 0.66-0.93)
      were collectively identified as factors contributing significantly to lower the
      probability of satisfactory glycaemic control. CONCLUSIONS: The study outcomes
      may prove useful for identifying paediatric patients at risk of having
      unsatisfactory glycaemic control, and who could require more extensive
      monitoring, support, or targeted interventions.

PMID- 28767735
TI  - Engaging the CD40-CD40L pathway augments T-helper cell responses and improves
      control of Mycobacterium tuberculosis infection.
AB  - Mycobacterium tuberculosis (Mtb) impairs dendritic cell (DC) functions and
      induces suboptimal antigen-specific CD4 T cell immune responses that are poorly
      protective. Mucosal T-helper cells producing IFN-gamma (Th1) and IL-17 (Th17) are
      important for protecting against tuberculosis (TB), but the mechanisms by which
      DCs generate antigen-specific T-helper responses during Mtb infection are not
      well defined. We previously reported that Mtb impairs CD40 expression on DCs and
      restricts Th1 and Th17 responses. We now demonstrate that CD40-dependent
      costimulation is required to generate IL-17 responses to Mtb. CD40-deficient DCs
      were unable to induce antigen-specific IL-17 responses after Mtb infection
      despite the production of Th17-polarizing innate cytokines. Disrupting the
      interaction between CD40 on DCs and its ligand CD40L on antigen-specific CD4 T
      cells, genetically or via antibody blockade, significantly reduced antigen
      specific IL-17 responses. Importantly, engaging CD40 on DCs with a multimeric
      CD40 agonist (CD40LT) enhanced antigen-specific IL-17 generation in ex vivo DC-T
      cell co-culture assays. Further, intratracheal instillation of Mtb-infected DCs
      treated with CD40LT significantly augmented antigen-specific Th17 responses in
      vivo in the lungs and lung-draining lymph nodes of mice. Finally, we show that
      boosting CD40-CD40L interactions promoted balanced Th1/Th17 responses in a
      setting of mucosal DC transfer, and conferred enhanced control of lung bacterial
      burdens following aerosol challenge with Mtb. Our results demonstrate that CD40
      costimulation by DCs plays an important role in generating antigen-specific Th17
      cells and targeting the CD40-CD40L pathway represents a novel strategy to improve
      adaptive immunity to TB.

PMID- 28767736
TI  - Cigarette smoke induced autophagy-impairment regulates AMD pathogenesis
      mechanisms in ARPE-19 cells.
AB  - Age related macular degeneration (AMD) is one of the leading causes of blindness.
      Genetics, environmental insult, and age-related factors all play a key role in
      altering proteostasis, the homeostatic process regulating protein synthesis,
      degradation and processing. These factors also play a role in the pathogenesis of
      AMD and it has been well established that cigarette smoking (CS) initiates AMD
      pathogenic mechanisms. The primary goal of this study is to elucidate whether CS
      can induce proteostasis/autophagy-impairment in retinal pigment epithelial (RPE)
      cells. In our preliminary analysis, it was found that cigarette smoke extract
      (CSE) induces accumulation of ubiquitinated proteins in the insoluble protein
      fraction (p < 0.01), which was subsequently mitigated through cysteamine (p <
      0.01) or fisetin (p < 0.05) treatment. Further, it was verified that these CSE
      induced ubiquitinated proteins accumulated in the peri-nuclear spaces (p<0.05)
      that were cleared- off with cysteamine (p < 0.05) or fisetin (p < 0.05).
      Moreover, CSE-induced aggresome-formation (LC3B-GFP and Ub-RFP co-localization)
      and autophagy-flux impairment was significantly (p<0.01) mitigated by cysteamine
      (p<0.05) or fisetin (p<0.05) treatment, indicating the restoration of CSE
      mediated autophagy-impairment. CSE treatment was also found to induce
      intracellular reactive oxygen species (ROS, p < 0.001) while impacting cell
      viability (p < 0.001), which was quantified using CMH2DCFDA-dye (ROS) and MTS
      (proliferation) or propodium iodide staining (cell viability) assays,
      respectively. Moreover, cysteamine and fisetin treatment ameliorated CS-mediated
      ROS production (p < 0.05) and diminished cell viability (p < 0.05). Lastly, CSE
      was found to induce cellular senescence (p < 0.001), which was significantly
      ameliorated by cysteamine (p < 0.001) or fisetin (p < 0.001). In conclusion, our
      study indicates that CS induced proteostasis/autophagy-impairment regulates
      mechanisms associated with AMD pathogenesis. Moreover, autophagy-inducing drugs
      such as cysteamine or fisetin can ameliorate AMD pathogenesis mechanisms that
      warrant further investigation in pre-clinical murine models.

PMID- 28767738
TI  - Defined Combinations of Cryomedia and Thawing Extenders Influence the Viable X-Y
      Boar Sperm Ratio in Vitro.
AB  - BACKGROUND: It is believed that plasma membrane X- and Y-chromosome bearing sperm
      are different; therefore the freezing and thawing process may affect X- and Y
      sperm differently. OBJECTIVE: The objective of this study was to investigate the
      effect of cryomedia and thawing extenders on the survival of X and Y-sperm.
      MATERIALS AND METHODS: Three different cryomedia and thawing extenders were
      compared. Viable motile sperm were separated using a swim-up technique. Real-time
      PCR was used to identify the sperm type. RESULTS: Using CryoA for freezing and
      Beltsville-Thawing-Solution (BTS) as the thawing extender yielded significantly
      higher numbers of viable motile Y sperm (64 percent) than control (48 percent) (P
      < 0.01). Conversely, semen freezing with CryoC and thawing with Androstar Plus
      gave a significantly lower number of viable motile Y sperm (32 percent) than
      control (51 percent). CONCLUSION: Our results revealed that defined combinations
      of cryomedia and thawing extenders significantly altered the survival ratio of
      frozen-thawed X-Y sperm in vitro, which has potential implications for artificial
      insemination.

PMID- 28767737
TI  - Tissue engineering potential of human dermis-isolated adult stem cells from
      multiple anatomical locations.
AB  - Abundance and accessibility render skin-derived stem cells an attractive cell
      source for tissue engineering applications. Toward assessing their utility, the
      variability of constructs engineered from human dermis-isolated adult stem
      (hDIAS) cells was examined with respect to different anatomical locations
      (foreskin, breast, and abdominal skin), both in vitro and in a subcutaneous,
      athymic mouse model. All anatomical locations yielded hDIAS cells with multi
      lineage differentiation potentials, though adipogenesis was not seen for foreskin
      derived hDIAS cells. Using engineered cartilage as a model, tissue engineered
      constructs from hDIAS cells were compared. Construct morphology differed by
      location. The mechanical properties of human foreskin- and abdominal skin-derived
      constructs were similar at implantation, remaining comparable after 4 additional
      weeks of culture in vivo. Breast skin-derived constructs were not mechanically
      testable. For all groups, no signs of abnormality were observed in the host.
      Addition of aggregate redifferentiation culture prior to construct formation
      improved chondrogenic differentiation of foreskin-derived hDIAS cells, as evident
      by increases in glycosaminoglycan and collagen contents. More robust Alcian blue
      staining and homogeneous cell populations were also observed compared to
      controls. Human DIAS cells elicited no adverse host responses, reacted positively
      to chondrogenic regimens, and possessed multi-lineage differentiation potential
      with the caveat that efficacy may differ by anatomical origin of the skin. Taken
      together, these results suggest that hDIAS cells hold promise as a potential cell
      source for a number of tissue engineering applications.

PMID- 28767739
TI  - Follicle Development in Grafted Mouse Ovaries after Vitrification Processes Under
      Static Magnetic Field.
AB  - BACKGROUND: Ovarian cryopreservation has emerged as an important method of
      fertility preservation. Magnetic field enhanced cryopreservation has been
      considered in recent times as a promising type of ovarian cryopreservation but
      the effectiveness of the process is still not clear. OBJECTIVE: The aim of the
      present study was to investigate the effect of applying 1-mT SMF (static magnetic
      field) on the vitrification of ovarian tissue and the follow-up investigation of
      the morphology and functions of vitrified- warmed ovarian tissue after
      transplantation. MATERIALS AND METHODS: Ovaries of 6-8 week-old female mice from
      the Naval Medical Research Institute (NMRI) were exposed of the static magnetic
      field during different steps of the vitrification process. Immunohistological
      studies were performed on the ovaries. RESULTS: The mean percentage of damaged
      primordial follicles was lowest in control group and the group with ovaries
      exposed to magnetic field during the equilibration step. The latter group also
      had the highest percentage of intact primordial follicles after transplantation.
      CONCLUSION: Exposure of mice ovaries to static magnetic field during first step
      of vitrification process (the equilibration step) resulted in greater resistance
      against injury.

PMID- 28767740
TI  - Cryopreservation of Waigieu Seaperch (Psammoperca waigiensis) Sperm.
AB  - BACKGROUND: The cryopreservation protocols have been applied for sperm
      prevervation of many fish species, but have not been developed for Waigieu
      seaperch Psammoperca waigiensis, an important aquaculture species in Vietnam.
      OBJECTIVE: The objectives of this study were to find the best cryoprotectant,
      extender, freezing method and dilution ratio for sperm cryopreservation of
      Waigieu seaperch. MATERIALS AND METHODS: An effective protocol was established by
      comparing different cryodiluents created by mixing various cryoprotectants and
      extenders. The different freezing methods and dilution ratios were also used in
      an effective protocol. The motility (MOT), straight-linear velocity (VSL) and
      fertility rates of post-thawed sperm were comparable to that of fresh sperm.
      RESULTS: The results indicated that at ratio of 1:3 in cryodiluent contained ASP
      (artificial seminal plasma) as extender supplement 10 percent DMSO as
      cryoprotectant and cryopreserved with the freezing method as two steps, reached
      the best MOT and VSL of post-thawed sperm. The fertilization rate and hatching
      rate of the post-thawed sperm cryopreserved for 1 week, 1 month, or 1 year in
      liquid nitrogen (66.93 +/- 0.93 percent and 44.16 +/- 1.47 percent, 65.40 +/-
      1.11 percent and 43.88 +/- 1.54 percent, or 65.13 +/- 1.31 percent and 43.24 +/-
      1.41 percent) were similar to that of fresh sperm (68.67 +/- 1.27 percent and
      45.12 +/- 1.92 percent). CONCLUSION: Using cryodiluent contained the ASP as
      extender and 10 percent DMSO as cryoprotectant to semen at the ratio of 1:3 (v/v)
      in the freezing method as two steps (-76 degree C for 5 minutes and -196 degree
      C) is an effective protocol for cryopreservation, especially hatching success of
      egg fertilized by post-thawed sperm of Waigieu seaperch.

PMID- 28767741
TI  - Antioxidant Effect of Xanthan Gum on Ram Sperm after Freezing and Thawing.
AB  - BACKGROUND: Xanthan gum is used as thickener in media to preserve food products,
      having cryoprotectant and antioxidant properties that may be relevant for sperm
      cryopreservation. OBJECTIVE: To evaluate the effects of adding xanthan gum to
      freezing extenders on post-thawing quality and oxidant activity of ram sperm.
      METHODS: Ejaculates from seven rams extended TRIS-egg yolk-glycerol were split in
      three treatments including xanthan gum (0.15%; 0.20%; and 0.25%) and a control
      with no xanthan gum. RESULTS: After thawing, motility and production of reactive
      oxygen species (ROS) with 0.20% and 0.25% xanthan gum were lower than for the
      control (P < 0.05), but mitochondrial functionality and integrity of membrane,
      acrosome and DNA did not differ (P > 0.05). Xanthan gum at 0.20% and 0.25% may be
      an efficient antioxidant for frozen-thawed ram sperm, due to the reduction in ROS
      production.

PMID- 28767742
TI  - Basic Fibroblast Growth Factor Improved Angiogenesis of Vitrified Human Ovarian
      Tissues after in vitro Culture and Xenotransplantation.
AB  - BACKGROUND: Basic fibroblast growth factor is a potent angiogenic factor.
      OBJECTIVE: To study the concentration and in vitro culture time of bFGF that
      maximize the angiogenesis for transplanted human ovarian tissues. MATERIALS AND
      METHODS: Vitrified and rewarmed human ovarian tissues were cultured in vitro with
      bFGF (0, 25, 50, 100, 150 and 200 ng/ml) for different periods (1 h, 2 d, 5 d and
      7 d) before transplantation. The effect of bFGF on follicle survival was studied
      by evaluating the pregraft group, control group (no bFGF) and bFGF-treated group.
      CD34, Ki-67 and AC-3 immuno-histochemical (IHC) staining and histological
      analysis was used to evaluate angiogenesis, proliferration, apoptosis and
      follicular quantity. RESULTS: Treatments with 100 and 150 ng/ml bFGF improved the
      angiogenesis for grafted human ovarian tissues after in vitro culture for 2 days.
      The proliferation and survival of follicles were significantly increased.
      CONCLUSION: bFGF improved the quality of vitrified-warmed human ovarian tissues
      after transplantation.

PMID- 28767743
TI  - Long Term Conservation at -80 degree C of Pinus radiata Embryogenic Cell Lines:
      Recovery, Maturation and Germination.
AB  - BACKGROUND: Pinus radiata is an economically important conifer, and somatic
      embryogenesis is being currently used for its propagation. But the embryogenic
      competence of cultures decreases with culture age. To cope with this,
      cryopreservation protocols have been developed lately for different Pinus
      species. Although cryopreservation reduces the costs associated with embryogenic
      cultures maintenance, the initial investment and the maintenance of cryotanks are
      expensive when dealing with somatic embryogenesis basic research issues.
      OBJECTIVE: To study the feasibility of storing embryogenic cell lines at -80
      degree C for over a year. MATERIALS AND METHODS: The feasibility of the
      conservation method was assessed in terms of recovery, maturation and germination
      rates. RESULTS: The recovery rates were up to 77 percnt;, and maturation and
      germination rates were 86 percnt; and 83 percnt;, respectively. CONCLUSION: The
      work described here is a simple and low-cost protocol that enables successful
      conservation of embryogenic cell lines for over a year.

PMID- 28767744
TI  - Effects of Washing Protocols on Cryosurvival of Spermatozoa from West African
      Dwarf Goat Bucks.
AB  - BACKGROUND: Sperm washing in some species helps remove the detrimental effect of
      enzymes secreted from the bulbourethral gland, but such an effect has not been
      evaluated for cryopreserved sperm obtained from West African Dwarf (WAD) goat
      bucks. OBJECTIVE: This study evaluated the effects of washing protocols on the
      viability parameters of spermatozoa obtained from WAD goat bucks prior to
      cryopreservation. MATERIALS AND METHODS: Semen samples collected from WAD goat
      bucks with the aid of artificial vagina were subjected to washing protocols by
      centrifuging once, twice and thrice while the control group was not washed.
      Following washing semen samples were diluted in Tris-based extenders,
      cryopreserved for 30 days in liquid nitrogen. RESULTS: Sperm motility, acrosome
      integrity, live spermatozoa and arginase activity were higher, and
      malondialdehyde (MDA) concentration was reduced in semen washed prior to
      cryopreservation compared to the control. CONCLUSION: Semen washing improved the
      quality.

PMID- 28767745
TI  - The Cold Hardiness of Phrynocephalus erythrurus, the Lizard Living at Highest
      Altitude in the World.
AB  - BACKGROUND: Phrynocephalus erythrurus living at Qinghai-Tibet Plateau, is
      believed to be the highest lizard in the world, but we know little about how
      these lizards cope with very low temperatures in winter. OBJECTIVE: The aim of
      this study was to find the difference of the lizards before and after cold
      acclimatization. MATERIALS AND METHODS: In this study the limit of supercooling
      and inoculative freezing, the concentration of four organic osmolytes, and the
      activity of lactate dehydrogenase in the plasma were measured in samples shortly
      after capture and in other samples after 7~8 weeks of acclimatization at 2~4
      degree C. RESULTS: Animals acquired an ability to undergo deeper supercooling and
      inoculative freezing through the course of acclimatization. We find no regular
      changes of the four organic osmolytes after the acclimatization. CONCLUSION: We
      think that this species of lizard is partly freeze-tolerant and conclude that it
      uses supercooling to survive in winter.

PMID- 28767746
TI  - Exogenous Catalase and Pyruvate Dehydrogenase Improve Survival and Regeneration
      and Affect Oxidative Stress in Cryopreserved Dendrobium nobile Protocorm-like
      Bodies.
AB  - BACKGROUND: Reactive oxygen species (ROS)-induced oxidative damage is responsible
      for viability loss in plant tissues following cryopreservation. Antioxidants may
      improve viability by preventing or repairing the injury. OBJECTIVE: This work
      aimed at studying the effect of catalase (CAT) and pyruvate dehydrogenase (PDH),
      which are involved in ROS metabolism and are differentially expressed during
      pollen cryopreservation, for cryopreservation of Dendrobium nobile Lindl. 'Hamana
      Lake Dream' protocorm-like bodies (PLBs). MATERIALS AND METHODS: Different
      concentrations of exogenous CAT or PDH were added at the loading, PVS2 treatment,
      unloading steps during vitrification-cryopreservation of PLBs. Their survival and
      regeneration were evaluated and correlated with physiological oxidative indexes.
      RESULTS: PLB survival increased significantly when CAT and PDH were added
      separately to the unloading solution at a suitable concentration. CAT at 400 U.ml
      1 increased PLB survival and regeneration by 33.5 and 14.6 percent respectively.
      It had no impact on the production of superoxide anion radical (.O2-) and on
      superoxide dismutase (SOD) activity, but it reduced the hydrogen peroxide (H2O2)
      and malondialdehyde (MDA) contents and enhanced ascorbic acid (AsA) and
      endogenous CAT levels compared to PLBs cryopreserved using the standard
      vitrification protocol (CK1). PDH at 0.1 U.ml-1 significantly improved PLB
      survival (by 2.5 percent), but it had no marked effect on regeneration compared
      to the CK1 group. It induced the same variations in .O2-, AsA and endogenous CAT
      levels that were observed following CAT addition. However, PDH did not affect the
      H2O2 and MDA content but significantly increased SOD activity. CONCLUSION: These
      results indicate that the addition of 400 U.ml-1 CAT and 0.1 U.ml-1 PDH at the
      unloading step increased survival of cryopreserved PLBs and that this improvement
      was associated with scavenging of H2O2 and the repair of oxidative damage.
      Exogenous CAT also significantly improved PLB regeneration after
      cryopreservation, while PDH had no obvious effect. The effect of exogenous CAT on
      PLB survival and regeneration was stronger than that of PDH, which may be due to
      the increased SOD activity by PDH addition.

PMID- 28767747
TI  - Determination of an Optimal Membrane-permeable Cryoprotectant Addition and
      Dilution Protocol for Water Buffalo Spermatozoa.
AB  - BACKGROUND: There is a possibility to reduce the toxicity of glycerol and osmotic
      stress of DMSO by lowering their concentrations in freezing extenders. OBJECTIVE:
      To investigate the effect of glycerol and DMSO in tris-citric acid based extender
      on post- thaw quality of buffalo (Bubalus bubalis) bull spermatozoa. MATERIALS
      AND METHODS: Semen was collected from five adult buffalo bulls with artificial
      vagina. Five aliquots of semen per bull were separated for dilution with the
      treatment extenders. The first aliquot was diluted at 37C with 6 percent glycerol
      (T1). The second aliquot was diluted at 37C with extenders containing 4.5 percent
      glycerol and 1.5 percent DMSO (T2). The third aliquot was diluted with extenders
      containing 4.5 percent glycerol at 37C and 1.5 percent DMSO at 4S (T3). The
      fourth aliquot was diluted with extenders containing 1.5 percent DMSO at 37C and
      4.5 percent glycerol at 4S (T4). The fifth aliquot was diluted with extender
      containing 2.5percent DMSO at 37 as well as at 4C (T5). The final concentration
      of spermatozoa was 50*106/ml in all the treatment groups. Semen was cooled from
      37 to 4C in 2 h and equilibration was done at 4 C for 4 h. Later on, packing of
      cooled semen was undertaken in 0.54 ml French straws and frozen in a programmable
      cell freezer. RESULTS: At post thawing, treatment groups T1 and T2 yielded
      significant (P < 0.05) outcome for CASA parameters, longevity, acrosomal
      integrity, plasma membrane integrity, mitochondrial transmembrane potential and
      DNA integrity. CONCLUSION: We concluded that by decreasing glycerol concentration
      (4.5 percent) and combining it with DMSO (1.5 percent) at 37C (T2) in tris-citric
      acid based extender provided similar results to those observed when glycerol (6
      percent) alone is used at 37C (T1) for improving the post-thaw quality of buffalo
      bull spermatozoa.

PMID- 28767748
TI  - Hop Powdery Mildew (Podosphaera macularis) Spore Cryopreservation.
AB  - BACKGROUND: Hop powdery mildew (HPM), Podosphaera macularis, an important disease
      organism for hops, is an obligate parasite, requiring constant culture on living
      plant tissue for strain maintenance. OBJECTIVE: This study determined the
      parameters required to successfully cryopreserve HPM spores for the first time
      and reduce the need for constant culture. MATERIALS AND METHODS: Spores of an
      Oregon HPM strain, OSU C-100 were desiccated over silica gel for 2-10 h to
      determine the spore moisture content (MC). Regrowth of the hyphae before and
      after drying and liquid nitrogen exposure was determined on glass slides and leaf
      discs of several susceptible hop cultivars. A second mixture of strains was later
      tested with the protocol. RESULTS: Desiccation to an optimal 2-3 percent MC
      produced hyphal growth on slides and infection of leaf discs. The OSU C-100 HPM
      spore strain required 8-10 h desiccation to reach 2-3 percent MC while the mixed
      strains required 6-8 h due to slightly different MC when collected. CONCLUSION:
      HPM strains should be placed in cryovials, dried to 2-3 percent MC over silica
      gel, cryopreserved by direct immersion in liquid nitrogen. They can be rewarmed
      for 1 min each in 45C and 20C water and the viability tested on isolated leaf
      discs.

PMID- 28767749
TI  - ?

PMID- 28767750
TI  - ?

PMID- 28767751
TI  - [An experience of history plan of nursing family assistance model].
AB  - Report on the use of a model nursing family assistance history and care plan,
      presented by teachers and students from a nursing school.

PMID- 28767752
TI  - [Respiratory exercises].
AB  - The author, who today is entirely dedicated to orienting others on respiratory
      exercises and describes those that serve to teach diaphragm respiration, increase
      pulmonary capacity, correct posture, as well as, emergency exercises for cases of
      asthmatic attacks.

PMID- 28767753
TI  - ?

PMID- 28767754
TI  - [Gradual development of Nutrition instruction in University of Sao Paulo's
      Nursing School.]

PMID- 28767755
TI  - [Anti-hipertensive agents en general nursing].
AB  - The author comments about the more commonly used anti-hipertensive agents in the
      nurse-yard, emphasizing the nurse's participation which becomes gradually more
      important for the complete success of the medical prescription.

PMID- 28767756
TI  - [The home visit as nursing assistance method for the family].
AB  - Describes the importance, the goas and the methodology of home visit, as well as
      the steps for the home visiting services organization in health centers or
      hospitals.

PMID- 28767757
TI  - [Teaching Medical Surgical Nursing in Specialization Course at the School of
      Nursing of the University of Sao Paulo - Evaluation about the program developed
      in 1976].
AB  - The authors analyse the program of Medical Surgical Nursing II of the School of
      Nursing of the University of Sao Paulo, developed in 1976. Based on the
      evaluation made by teachers, students and nurses of the clinical practice units,
      they concluded that the program seems to attempt its main finality contributing
      in nurse's formation with specialized prepare to an eficient action in recovery
      room and emergency and intensive care units.

PMID- 28767758
TI  - [Scientific studies' analyses].
AB  - A guide to analyse scientifics studies, effect of investigations, is concepted in
      this work; are included questions about the planning, execution and report of the
      research.

PMID- 28767760
TI  - ?

PMID- 28767759
TI  - [STUDY ABOUT PATIENT'S RELIGIOUS NEED IN PRESURGICAL STAGE].
AB  - A study of problems related to nursing assistance of patient's religious need in
      presurgical stage. Two hundred adult patients of both sexes admitted in three
      hospitals of Sao Paulo were interviewed. One hospital was a governmental
      institution, and two were private. Patient's interviews were made by means of a
      form containing open questions, which were filled out by the researcher according
      the patient's answers. Therefore it was able to reinforce the existent thought of
      the human being having a theological instinct, for almost the totality of the
      studied patients believed in God and showed their beliefs with unlike religious
      practices. Patients belonged to different denominations, most of them roman
      catholics. The common problem found among patients was the fear of surgery, which
      decreased with religious practices. In such a way, it was pointed out the
      significance of nursing service of admission, for this was the main nursing
      problem found in this study: large number of patients were unable to realize
      their practices while in hospital, given the lack of orientation the main reazon
      for that. Patients also suggested what they would like to receive from the
      hospital to attend their religious need. All the suggestions could be solved
      through the application of nursing process, considering the patient's dependence
      degree.

PMID- 28767761
TI  - ?

PMID- 28767762
TI  - ?

PMID- 28767763
TI  - [Nursing care planning of patient in the surgical period: teaching of nursing
      student - I].
AB  - The authors, teacher of Operating Room Nursing, describe how to teach the nursing
      care of patient in the surgical period. Relation is made between knowledge and
      technic utilized. The importance of planning these is emphatized, as his
      contents.

PMID- 28767764
TI  - [Words related to health psychological meaning for nursing students].
AB  - Semantic Differential Scales technique of Charles Osgood was applied to 246
      nursing students at their first week of professional course, to measure the
      psychological meaning of the words: Health, Physician, Pain, Hospital, Nurse and
      Illness In almost all words studied was found a high index of stereotipy related
      to valorative, potential and activity factors. Index of internal con-tradition
      were found related with Illness, Nurse and Hospital words.

PMID- 28767765
TI  - [Applying the nursing process to patient care in the operating room].
AB  - The article proposes to approach the application of the nursing process to
      patient care in the operating room, it gives a theorical basis and examples from
      the clinical pratices.

PMID- 28767766
TI  - [Dispneic patient: general conditions (Part I)].
AB  - The author makes a general approach about dyspnea and the importance of nursing
      assistance for the patient in this eventuality. It's studied the general
      conditions about this patient and nursing's actuation.

PMID- 28767767
TI  - [Applicability of nutrition knowledge by nurses graduated in University of Sao
      Paulo's Nursing School].
AB  - The applicability of nutrition knowledge in nursing it was studied The research
      covers the nurses graduated in the University of Sao Paulo's Nursing School, in
      1975.

PMID- 28767768
TI  - [Valuation of a antisepsis method for surgical skin area in a heart surgery
      patient's group - with a product basead on POVIDONE IODINE, previous note].
AB  - Previous note of a comparative study between usual method of antisepsis of
      surgical skin area and a standard method making use of povidone iodine in groups
      of patients undergone Heart Surgery, in a determinate hospital of the city of Sao
      Paulo. This study demonstrated that in patients where it was used the standard
      method with povidone iodine in the antissepsis of the surgical skin area, the
      infection rate of the surgical incision was significantly smaller than in
      patients in which it was used the conventional methods of antisepsis.

PMID- 28767769
TI  - The Quebec Sleep Questionnaire on quality of life in patients with obstructive
      sleep apnea: translation into Portuguese and cross-cultural adaptation for use in
      Brazil.
AB  - OBJECTIVE: To translate the Quebec Sleep Questionnaire (QSQ), a specific
      instrument for the assessment of quality of life in patients with sleep
      obstructive apnea, into Portuguese and to create a version that is cross
      culturally adapted for use in Brazil. METHODS: The Portuguese-language version
      was developed according to a rigorous methodology, which included the following
      steps: preparation; translation from English into Portuguese in three versions;
      reconciliation to a single version; back-translation of that version into
      English; comparison and harmonization of the back-translation with the original
      version; review of the Portuguese-language version; cognitive debriefing; text
      review; and arrival at the final version. RESULTS: The Portuguese-language
      version of the QSQ for use in Brazil had a clarity score, as measured by
      cognitive debriefing, ranging from 0.81 to 0.99, demonstrating the consistency of
      translation and cross-cultural adaptation processes. CONCLUSIONS: The process of
      translating the QSQ into Portuguese and creating a version that is cross
      culturally adapted for use in Brazil produced a valid instrument to assess the
      quality of life in patients with obstructive sleep apnea.

PMID- 28767770
TI  - Effects of continuous positive airway pressure on blood pressure in patients with
      resistant hypertension and obstructive sleep apnea: a systematic review and meta
      analysis of six randomized controlled trials.
AB  - OBJECTIVE: To evaluate systematically the effects of continuous positive airway
      pressure (CPAP) on blood pressure in patients with resistant hypertension and
      obstructive sleep apnea (OSA). METHODS: The Cochrane Library, PubMed,
      ScienceDirect, and the Web of Science were searched for studies investigating the
      effects of CPAP on blood pressure in patients with resistant hypertension and
      OSA. The selected studies underwent quality assessment and meta-analysis, as well
      as being tested for heterogeneity. RESULTS: Six randomized controlled trials were
      included in the meta-analysis. The pooled estimates of the changes in mean
      systolic blood pressure and mean diastolic blood pressure (as assessed by 24-h
      ambulatory blood pressure monitoring) were -5.40 mmHg (95% CI: -9.17 to -1.64; p
      = 0.001; I2 = 74%) and -3.86 mmHg (95% CI: -6.41 to -1.30; p = 0.00001; I2 =
      79%), respectively. CONCLUSIONS: CPAP therapy can significantly reduce blood
      pressure in patients with resistant hypertension and OSA.

PMID- 28767771
TI  - Parapneumonic pleural effusion: early versus late thoracoscopy.
AB  - OBJECTIVE: To evaluate the best time to perform thoracoscopy for the treatment of
      complicated parapneumonic pleural effusion in the fibrinopurulent phase in
      patients <= 14 years of age, regarding the postoperative evolution and occurrence
      of complications. METHODS: This was a retrospective comparative study involving
      patients with parapneumonic pleural effusion presenting with septations or
      loculations on chest ultrasound who underwent thoracoscopy between January of
      2000 and January of 2013. The patients were divided into two groups: early
      thoracoscopy (ET), performed by day 5 of hospitalization; and late thoracoscopy
      (LT), performed after day 5 of hospitalization. RESULTS: We included 60 patients,
      30 in each group. The mean age was 3.4 years; 28 patients (46.7%) were male; and
      47 (78.3%) underwent primary thoracoscopy (no previous simple drainage). The two
      groups were similar regarding gender, age, weight, and type of thoracoscopy (p >
      0.05 for all). There was a significant difference between the ET and the LT
      groups regarding the length of the hospital stay (14.5 days vs. 21.7 days; p <
      0.001). There were also significant differences between the groups regarding the
      duration of fever in days; the total number of days from admission to the
      initiation of drainage; and the total number of days with the drain in place.
      Eight patients (13.6%) had at least one post-thoracoscopy complication, there
      being no difference between the groups. There were no deaths. CONCLUSIONS:
      Performing ET by day 5 of hospitalization was associated with shorter hospital
      stays, shorter duration of drainage, and shorter duration of fever, although not
      with a higher frequency of complications, requiring ICU admission, or requiring
      blood transfusion.

PMID- 28767772
TI  - Chest CT findings in patients with dysphagia and aspiration: a systematic review.
AB  - The objective of this systematic review was to characterize chest CT findings in
      patients with dysphagia and pulmonary aspiration, identifying the characteristics
      and the methods used. The studies were selected from among those indexed in the
      Brazilian Virtual Library of Health, LILACS, Indice Bibliografico Espanol de
      Ciencias de la Salud, Medline, Cochrane Library, SciELO, and PubMed databases.
      The search was carried out between June and July of 2016. Five articles were
      included and reviewed, all of them carried out in the last five years, published
      in English, and coming from different countries. The sample size in the selected
      studies ranged from 43 to 56 patients, with a predominance of adult and elderly
      subjects. The tomographic findings in patients with dysphagia-related aspiration
      were varied, including bronchiectasis, bronchial wall thickening, pulmonary
      nodules, consolidations, pleural effusion, ground-glass attenuation, atelectasis,
      septal thickening, fibrosis, and air trapping. Evidence suggests that chest CT
      findings in patients with aspiration are diverse. In this review, it was not
      possible to establish a consensus that could characterize a pattern of pulmonary
      aspiration in patients with dysphagia, further studies of the topic being needed.

PMID- 28767775
TI  - ?

PMID- 28767773
TI  - Long-acting muscarinic antagonists vs. long-acting beta 2 agonists in COPD
      exacerbations: a systematic review and meta-analysis.
AB  - OBJECTIVE: To determine whether long-acting muscarinic antagonists (LAMAs)
      provide superior therapeutic effects over long-acting beta2 agonists (LABAs) for
      preventing COPD exacerbations. METHODS: This was a systematic review and meta
      analysis of randomized clinical trials involving patients with stable, moderate
      to severe COPD according to the Global Initiative for Chronic Obstructive Lung
      Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or
      glycopyrronium), followed for at least 12 weeks and compared with controls using
      a LABA in isolation or in combination with a corticosteroid. RESULTS: A total of
      2,622 studies were analyzed for possible inclusion on the basis of their title
      and abstract; 9 studies (17,120 participants) were included in the analysis. In
      comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate
      ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of
      patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94;
      p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78;
      95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR
      = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was
      moderate for all outcomes. CONCLUSIONS: The major findings of this systematic
      review and meta-analysis were that LAMAs significantly reduced the exacerbation
      rate (exacerbation episodes/year), as well as the number of exacerbation
      episodes, of hospitalizations, and of serious adverse events.

PMID- 28767774
TI  - Factors associated with malnutrition in adolescent and adult patients with cystic
      fibrosis.
AB  - OBJECTIVE: To determine the prevalence of malnutrition in patients attending an
      adult cystic fibrosis (CF) program and to investigate the associations of
      malnutrition with the clinical characteristics of those patients. METHODS: This
      was a cross-sectional study involving patients with clinically stable CF patients
      (16 years of age or older). The patients underwent clinical assessment,
      nutritional assessments, pulmonary function tests, and pancreatic function
      assessment. They also completed a questionnaire regarding diet compliance. On the
      basis of their nutritional status, the patients were classified divided into
      three groups: adequate nutrition; at nutritional risk; and malnutrition. RESULTS:
      The study has included 73 patients (mean age, 25.6 +/- 7.3 years), 40 of whom
      (54.8%) were female. The mean body mass index was 21.0 +/- 3.0 kg/m2 and the mean
      FEV1 was 59.7 +/- 30.6% of predicted. In this sample of patients, 32 (43.8%), 23
      (31.5%), and 18 (24.7%) of the patients were allocated to the adequate nutrition,
      nutritional risk, and malnutrition groups, respectively. The logistic regression
      analysis identified three independent factors associated with the risk of
      malnutrition: Shwachman-Kulczycki score, percent predicted FEV1; and age.
      CONCLUSIONS: Malnutrition remains a common complication in adolescents and adults
      with CF, despite dietary advice. Malnutrition is associated with age, clinical
      severity, and lung function impairment.

PMID- 28767776
TI  - [Psychiatric nursing as the chosen field for practice].
AB  - Survey to fund the opinion of 59 nursing students,about the reason for not
      choosing psychiatric musing as the field for future practice. These students were
      from four schools of nursing of the Great Sao Paulo.

PMID- 28767777
TI  - [The nurse facing increased intracranial pressure patient].
AB  - A review of increased intracranial pressure. Physiopathological aspects and
      preventive measures, which can be adopted by nurses, in the imminence of sudden
      increased intracranial pressure.

PMID- 28767778
TI  - [Protein-calorie malnutrition in rats-response of protein-calorie malnourished
      rats to a nutritional protein deprivation].
AB  - The author studies the effect of nutritional protein deprivation on experimental
      models of marasmatic-kwashiorkor and marasmus in rats. The parameters used were
      quantity of nitrogen in liver and pancreas, and liver lipides.

PMID- 28767780
TI  - [Influence of obstetrical centers' blue-prints upon the nursing care of the woman
      in labor].
AB  - The blue-prints of three obstetrical centers were studied to determine their
      influence upon the activity of the nurse. For this purpose an analyses was made
      of the time spent and the activities performed by the nurse at the different
      departments of the obstetrical center. The findings revealed that, if an
      obstetrical center is not well planned, the nursing care of the woman in labor is
      impaired.

PMID- 28767779
TI  - [Nursing students help sick children throusih "play-intei view"].
AB  - Presenting and commenting on the significance of the employment of "play
      interview" in the situations of aid to sick children.

PMID- 28767781
TI  - [The community nursing in the nursing curriculum (part I)].
AB  - This is the first part of an article on community nursing. It refers to the basic
      concepts of health, public health and community nursing. It will be followed by a
      second part, relative to preparation for community nursing, containing
      suggestions for the inclusion of the community and preventive aspects in the
      nursing curriculum.

PMID- 28767782
TI  - [The nurse's responsabilities regarding to the assistance of righ-risk newborn].
AB  - The autohrs refer to the importance of the nurse's performance regarding the care
      of the high-risk newborn. Different aspects of assistance and education related
      to this problem are considered. They, also, emphasize the role of the nurse in
      keeping the parents informed about the conditions of their baby to help them to
      overcome the actual family crisis.

PMID- 28767783
TI  - [Dispneic patient: their's problematic (part II)].
AB  - The author presents the results of a study of the reactions of cardiac and
      pulmonary patients to an attach of dispnea. She discusses the prevalent problems
      and the desirable attitude of nursing personnel.

PMID- 28767784
TI  - ?

PMID- 28767785
TI  - [Relationship between nursing students and hospitalized children: analysis of two
      experiences].
AB  - Two different examples of relationship between students of pediatric nursing and
      hospitalized children are presented by the authours. The frequency of attained
      purposes are examined too.

PMID- 28767786
TI  - [Study about the regions for intramuscular injections].
AB  - Administration of drugs by intramuscular injections is a nursing procedure. The
      choice of the sites to be utilized need to be considered regarding advantages and
      disadvantages of each local. A data colection was started to know about the most
      utilized sites by nursing teachers and the hospital nurses, and the local pointed
      out by them for needle punction. It was verified that there is any
      differentiation in the choice of sites according the patient's age and sex and
      the knowledge of contraindications and complications of each sites for
      intramuscular injections. The data concluded that deltoidea, dorsogluteal and
      lateral thigh regions were the preferable one for both groups of nurses and the
      locations were not always anatomically right; for the choice of the site was
      considered the patient's age by 80% of the population. Only some mentioned
      contraindications and complications were according to consulted authors. The
      ventrogluteal region, supposed as the most save and suitable one by the authors,
      was the less mentioned by both groups of nurses.

PMID- 28767787
TI  - [Nursing problems and its conceptuation].
AB  - The author reviews the literature regarding "nursing problems" and comments on
      the employment of these concepts and its theoretical entanglement, establishing
      the difference among "nursing problems", "patient's problems" and "patient's
      needs".

PMID- 28767789
TI  - [The process of the fetal neck curve compression as a manner for circle
      diagnosis].

PMID- 28767788
TI  - [Nursing care to patientes under psychotropic drugs treatment].
AB  - Nursing care to patients under psychotropic drugs treatment is reported on by
      authors. The importance of the nurse's role in this specific treatment is
      emphasized.

PMID- 28767790
TI  - [Teaching the Apgar score to students of obstetric nursing].

PMID- 28767791
TI  - ?

PMID- 28767792
TI  - [Acceptance, empaty and emotional involvement in nurse-patient relationship].
AB  - In dealing with the patient, the nurse has always to have in mind that she is
      dealing with a human being. There are basic aspects in this personal relationship
      needed to the knowledge of the nurse to make this process therapeutic. Among
      these aspects we have acceptance, empaty and emotional involvement. These aspects
      we studied following bibliographical review, theorical conception and importance
      to the nurse-patient relationship. Situations that show accourance of those given
      aspects and the benefits brought to nurse-patient relationship are described.

PMID- 28767793
TI  - [Nursing intervention in surgery to prevent pulmonary complications].
AB  - The authors describe the predisposing factors of post-operative pulmonary
      complications (old age, malbalanced hydratation and nutrition, exacerbation of
      chronic obstructive pulmonary diseases) as well as the aggravating factors
      (anesthesia, immobilization in bed, abdominal distention, pain). They present the
      objectives of nursing intervention, pre and post operative measures to prevent
      pulmonary complications, early identification of clinical signs of respiratory
      failure, and treatment.

PMID- 28767794
TI  - [Prevention levels in occupational nursing].
AB  - The autor, based in nursing functions concepts of HENDERSON and of HORTA, and in
      the prevention levels of LEAVELL & CLARK, write about the of the occupational
      health nursing personnel in Brasil and describes their actions and activities.

PMID- 28767795
TI  - Surgery and the internet.

PMID- 28767796
TI  - Mortality predictors in patients with pelvic fractures from blunt trauma.
AB  - Objective:: to analyze the association of mortality with sociodemographic and
      clinical variables, as well as lesions and complication in patients with pelvic
      trauma due to blunt trauma. Methods:: we conducted a retrospective, observational
      study with five-year trauma record data. Death was considered as the main
      stratification variable for the analyzes. We used the Student t test to compare
      means, the Chi-Square or Fisher exact test for proportions, and the Wilcoxon-Mann
      Whitney test for medians. We analyzed the independent factors using a logistic
      regression model with penalized likelihood, based on the Wald tests, the Akaike
      Information Criterion (AIC) and the Schwarz Bayesian Information Criterion (BIC).
      Results:: of the 28 patients with blunt trauma fracture, 23 (82.1%) were men; 16
      (57.1%) were, in average, 38.8 years old (+/-17.3). There were 98 lesions or
      fractures in the 28 patients. As for severity, seven people had Injury Severity
      Score higher than 24 (25%). The mean hospital stay was 26.8 days (+/-22.4).
      Fifteen patients (53.6%) had ICU admission. Mortality was 21.4%. The analysis
      showed that age 50 years or more and presence of coagulopathy were factors
      independently associated with death. Conclusion:: pelvic fractures can have high
      mortality. In this study, mortality was higher than that described in the
      literature. Age above 50 years and the presence of coagulopathy are risk factors
      in this population.

PMID- 28767797
TI  - Evaluation of sepsis treatment with enteral glutamine in rats.
AB  - Objective:: to analyze the influence of glutamine on morphological and
      histological changes observed in the ileum, lung, kidney and liver of Wistar rats
      subjected to sepsis. Methods:: we induced sepsis by cecal ligature and puncture.
      We divided the animals in two groups: group A, control, with five animals, and
      group B, experience, with ten animals that received enteral glutamine two days
      before sepsis induction. We used histological analysis to rank the injury
      according to a score dependent on the injury severity and the affected organ. The
      sum of values assigned to each animal resulted in a final grade. We assessed the
      villi in the ileum, microgoticular steatosis in the liver, interstitial
      pneumonitis in the lungs, and vacuolation of the proximal convoluted tubules in
      the kidneys. Results:: cell lysis and destruction of the villi of the ileum were
      more intense in the control group when compared with animals receiving glutamine.
      In the kidney, we found more pronounced vacuolization in the proximal convoluted
      tubules in the control group compared with animals receiving glutamine. Both
      microgoticular steatosis and interstitial pneumonitis were similar between
      groups. Conclusion:: administration of enteral glutamine prior to sepsis
      preserved the histological structure.

PMID- 28767798
TI  - Conventional inguinal hernia repair with self-fixating mesh versus totally
      extraperitoneal laparoscopic repair with polypropylene mesh: early postoperative
      results.
AB  - Objective:: to evaluate the early postoperative results of inguinal hernia repair
      by the conventional technique with self-fixating mesh versus laparoscopic totally
      extraperitoneal repair with polypropylene mesh. We compared pain, surgical time
      and early complications. Methods:: this is a prospective, case-series study of 80
      consecutive patients treated in the surgical clinic of the Gaffree e Guinle
      University Hospital (HUGG). We included patients with unilateral inguinal hernia,
      not relapsed and operated only on an elective basis. We divided patients into two
      groups of 40 patients each, SF group (conventional technique using self-fixating
      mesh) and LP group (laparoscopic technique with polypropylene mesh). We followed
      patients up until the 45th postoperative day. Results:: of the 80 patients, 98.7%
      were male and the majority had indirect right inguinal hernias (Nyhus II). There
      was no difference between the groups studied in respect to pain and operative
      time. However, more complications occurred (seroma and hematoma) in the open
      surgery group. Conclusion:: both operations have proved feasible, safe and with
      minimal postoperative pain and a low operating time.

PMID- 28767799
TI  - Retrospective analysis of 103 diaphragmatic injuries in patients operated in a
      trauma center.
AB  - Objective:: to analyze the factors associated with death in patients with
      diaphragmatic injury treated at a trauma reference hospital. Methods:: we
      conducted a retrospective study of patients with diaphragm injury attended at the
      Risoleta Tolentino Neves Hospital of the Federal University of Minas Gerais,
      between January 2010 and December 2014. We used The Collector(r) database of
      trauma records (MD, USA). We gathered data on demographics, location of the
      diaphragmatic lesion, site and number of associated lesions, type of therapeutic
      approach, complications and Injury Severity Score (ISS). The variable of interest
      was the occurrence of death. Results:: we identified 103 patients and mortality
      was 16.5%. Penetrating lesions occurred in 98% of patients. Univariate analysis
      showed a mortality higher in patients whose treatment was non-operative, without
      closing of the defect (p=0.023), and lower in patients submitted to diaphragmatic
      suturing (p<0.001). The increase in the number of lesions was associated with an
      increase in mortality (p=0.048). In multivariate analysis, ISS>24 (OR=4.0,
      p=0.029) and diaphragmatic suturing (OR=0.76, p<0.001) were associated with
      mortality. Conclusion:: The findings indicate that the traumatic rupture of the
      diaphragm rarely presents as an isolated lesion, being frequently associated with
      injuries of other organs, especially the liver and hollow viscera. Mortality was
      higher among those with ISS>24.

PMID- 28767800
TI  - Prevalence of gallbladder cancer In patients submitted to cholecystectomy:
      experience of the University Hospital, Faculty of Medical Sciences, State
      University of Campinas - UNICAMP.
AB  - Objective:: to evaluate the prevalence of gallbladder carcinoma in patients
      submitted to cholecystectomy for chronic cholecystitis at the University Hospital
      of the State University of Campinas. Methods:: we conducted a retrospective
      prevalence study through the analysis of histological specimens from January 2010
      to May 2015. Results:: we analyzed 893 patient reports. Emergency
      cholecystectomies amounted to 144, and elective ones, 749 (16.2% and 83.8%,
      respectively). Regarding gender, 72.8% were female and 27.2% male. Gallbladder
      adenocarcinoma occurred in 12 patients (1.3%) and non-Hodgkin's lymphoma in one
      (0.1%). In patients with cancer, seven (53.8%) were associated with
      cholelithiasis and two (15.3%) with gallbladder polyps. Conclusion:: prevalence
      results of gallbladder adenocarcinoma in this study were similar to those of
      Western studies and the main risk factor was cholelithiasis, followed by the
      presence of gallbladder polyps.

PMID- 28767801
TI  - Predictors of mortality in patients submitted to nephrectomy for non-metastatic
      renal cell carcinoma at a referral center in Northeastern Brazil.
AB  - Objective:: to identify predictors of mortality in patients submitted to
      nephrectomy for non-metastatic renal cancer. Methods:: we conducted a
      retrospective cohort study based on the records of patients with renal cancer
      submitted to radical or partial nephrectomy at the Ceara Cancer Institute.
      Results:: we studied 117 patients, with mean and median age of 59.14 and 59
      years, respectively. The male gender was slightly predominant. The right kidney
      was most frequently affected (64%). The most common histopathological diagnosis
      was clear-cell carcinoma (77%). Stage pT1 and Fuhrman grade II were predominant.
      The only predictive variables of overall survival were pathological stage (pT)
      and lymph node involvement. Conclusion:: pathological stage (pT) and lymph node
      involvement are important prognostic factors in patients undergoing nephrectomy
      for non-metastatic renal cancer.

PMID- 28767802
TI  - Parathyroidectomy in chronic kidney disease: effects on weight gain and on
      quality of life improvement.
AB  - Objective:: to evaluate the benefit of parathyroidectomy in patients on
      hemodialysis, regarding nutritional and biochemical statuses, body composition
      and the health-related quality of life. Methods:: this is a longitudinal study
      involving 28 hemodialysis adult patients with severe secondary
      hyperparathyroidism evaluated before and one year after surgery. Inclusion
      criteria: parathyroid hormone levels exceeding ten times the upper normal range
      and end-stage renal disease in hemodialysis program. We used the body mass index
      to classify the nutritional status and the biodynamics analyzer to evaluate the
      body composition. Biochemical analysis included markers of lipid and bone
      metabolism. We assessed quality of life with the SF36 (Short Form Health Survey)
      questionnaire. All individuals underwent total parathyroidectomy with a forearm
      implant. Results:: there were significant gains in body weight (61.7 vs 66.0 kg,
      p<0.001), body cell mass (22.0 vs 24.5 kg/m2, p=0.05) and quality of life
      (p=0.001) after surgery. With respect to bone metabolism, intact PTH, calcium,
      phosphorus and alkaline phosphatase all stabilized and there were improvements in
      biochemical parameters such as albumin and hemoglobin. Conclusion::
      parathyroidectomy improves hemodialysis patient survival and is associated with
      weight and bone cell mass gain and improvement in health-related quality of life.

PMID- 28767803
TI  - Perioperative care in bariatric surgery in the context of the ACERTO project:
      reality versus surgeons assumptions in a Cuiaba hospital.
AB  - Objective:: to assess the level of knowledge among bariatric surgeons, about the
      recommendations of the ACERTO Project, correlating their assumptions on their
      perioperative prescriptions and the reality, according to the patients charts.
      Method:: we conducted a prospective, longitudinal, observational study comparing
      the assumptions of bariatric surgeons obtained through responses on a specific
      questionnaire with the reality found in clinical data from the hospital records.
      We analyzed the following variables: preoperative fasting, early postoperative
      feeding, intravenous hydration, perioperative antibiotic prophylaxis, use of
      abdominal drains, type of analgesia, and prophylaxis of nausea and vomiting. We
      confronted the responses of seven surgeons with data from 200 records of patients
      undergoing gastroplasty for morbid obesity. Results:: all interviewed surgeons
      knew the ACERTO Project. Five (72%) responded that they followed the protocol
      thoroughly. The median time of preoperative fasting found in the records was
      higher than the reported by the surgeons (p<0.05). Early postoperative feeding
      was prescribed for 96.5% of cases. The median volume of intravenous fluids
      prescribed in the first 24 hours was 4000ml, which was consistent with the
      interviews. There were no differences between the response in the questionnaire
      and the findings in the hospital records in relation to antibiotic prophylaxis,
      use of catheters and drains, analgesia and prophylaxis of nausea and vomiting.
      Conclusion:: the ACERTO Project was well practiced among the surveyed surgeons.
      There was a good correlation between their assumptions and the reality in
      perioperative care of patients undergoing bariatric surgery. However, there was a
      significant difference in preoperative fasting time.

PMID- 28767804
TI  - Partial stapled hemorrhoidopexy: clinical aspects and impact on anorectal
      physiology.
AB  - Objective:: to evaluate the impact of partial stapled hemorrhoidopexy on
      anorectal physiology, the complications related to this surgical technique, pain,
      postoperative bleeding and recurrence of hemorrhoidal disease one year after
      surgery. Methods:: this is a prospective, descriptive study in consecutive
      patients with mixed or internal hemorrhoidal disease, the internal component
      being classified as grade III or IV, undergoing partial stapled hemorrhoidopexy.
      Results:: we studied 17 patients, 82% of them with internal hemorrhoids grade III
      and 18% grade IV. The mean operative time was 09:09 minutes (07:03 to 12:13). The
      median pain in the immediate postoperative period evaluated by the numerical pain
      scale was one (0 to 7). The median time to return to work was nine days (4 to
      19). No patient had anal stenosis and 76% were satisfied with the surgery 90 days
      postoperatively. When comparing the preoperative manometry data with that
      measured 90 days after surgery, none of the variables studied showed
      statistically significant difference. There was no recurrence of hemorrhoidal
      disease with one year of postoperative follow-up. Conclusion:: partial stapled
      hemorrhoidopexy showed no impact on anorectal physiology, presenting low levels
      of complications and postoperative pain, without recurrence of hemorrhoidal
      disease in one year of follow-up.

PMID- 28767805
TI  - Incidence and risk factors for postoperative pulmonary complications in patients
      undergoing thoracic and abdominal surgeries.
AB  - Objective:: to determine the incidence of postoperative pulmonary complications
      in patients undergoing abdominal and thoracic surgery and investigate the risk
      factors for their occurrence. Methods:: we conducted a prospective, observational
      and analytical study with all the patients undergoing thoracic and abdominal
      surgeries at the Santo Antonio Hospital in Blumenau, SC. We collected data from
      medical records and structured interviews with patients, regarding the
      characteristics of patients and procedures. The outcome variable was the
      occurrence of postoperative pulmonary complications in the medical record.
      Results:: we studied 314 patients, 65.6% female, with an average age of 46.61
      years. Of the sample, 51.6% was ASA II, 55.7% of the surgeries were performed by
      laparoscopy or thoracoscopy, 85.4% were in the abdomen, and 61.5% were
      potentially contaminated and of medium-scale procedures. The average time of
      surgery was 126.65 minutes and the average length of hospital stay was 2.59 days.
      The incidence of postoperative pulmonary complications was 11.5%. The most common
      complications were respiratory failure, pleural effusion and pneumonia. The most
      important risk factor were diabetes, hospitalization for more than five days and
      the presence of pulmonary disease. Patients operated by laparoscopy or
      thoracoscopy had fewer complications. Conclusion:: postoperative pulmonary
      complications are frequent and factors associated with greatest risk were
      diabetes, prolonged hospitalization and presence of previous lung disease.

PMID- 28767806
TI  - Extracranial carotid stenosis: evidence based review.
AB  - Extracranial cerebrovascular disease is one of the most important causes of death
      and disability worldwide and its treatment is based on clinical and surgical
      strategies, the latter being performed by conventional or endovascular
      techniques. The management of stenosis of the carotid bifurcation is mainly aimed
      at preventing stroke and has been the subject of extensive investigation. The
      role of clinical treatment has been re-emphasized, but carotid endarterectomy
      remains the first-line treatment for symptomatic patients with 50% to 99%
      stenosis and for asymptomatic patients with 60% to 99% stenosis. Stent
      angioplasty is reserved for symptomatic patients with stenosis of 50% to 99% and
      at high risk for open surgery due to anatomical or clinical reasons. Currently,
      the endovascular procedure is not recommended for asymptomatic patients who are
      able to undergo conventional surgical treatment. Brazil presents a trend similar
      to that of other countries in North America and Europe, keeping endarterectomy as
      the main indication for the treatment of carotid stenosis and reserving the
      endovascular procedure for cases in which there are contraindications for the
      first intervention. However, we must improve our results by reducing
      complications, notably the overall mortality rate.

PMID- 28767807
TI  - Model of a training program in robotic surgery and its initial results.
AB  - Objective:: to describe the implementation of a training program in robotic
      surgery and to point the General Surgery procedures that can be performed with
      advantages using the robotic platform. Methods:: we conducted a retrospective
      analysis of data collected prospectively from the robotic surgery group in
      General and Colo-Retal Surgery at the Samaritan Hospital (Rio de Janeiro,
      Brazil), from October 2012 to December 2015. We describe the training stages and
      particularities. Results:: two hundred and ninety three robotic operations were
      performed in general surgery: 108 procedures for morbid obesity, 59 colorectal
      surgeries, 55 procedures in the esophago-gastric transition area, 16
      cholecystectomies, 27 abdominal wall hernioplasties, 13 inguinal hernioplasties,
      two gastrectomies with D2 lymphadenectomy, one vagotomy, two diaphragmatic
      hernioplasties, four liver surgeries, two adrenalectomies, two splenectomies, one
      pancreatectomy and one bilio-digestive anastomosis. The complication rate was
      2.4%, with no major complications. Conclusion:: the robotic surgery program of
      the Samaritan Hospital was safely implemented and with initial results better
      than the ones described in the current literature. There seems to be benefits in
      using the robotic platform in super-obese patients, re-operations of obesity
      surgery and hiatus hernias, giant and paraesophageal hiatus hernias, ventral
      hernias with multiple defects and rectal resections.

PMID- 28767808
TI  - Preliminary results of severe venous insufficiency treatment with thermal
      ablation of the great saphenous vein by endovascular technique with laser diode
      980nm developed in Brazil, associated with sclerotherapy with polidocanol.
AB  - The endovenous laser ablation (EVLA) of the insufficient saphenous vein has
      similar results to open conventional surgery, but less morbidity. The echo-guided
      polidocanol foam sclerotherapy technique has been used for the same purpose. The
      combined techniques may play a role for more severe diseases, such as those with
      varicose ulcers. An EVLA device (called VELAS) has been developed in the Optics
      and Photonics Research Center of USP-Sao Carlos in agreement with FMB-UNESP. In
      this study, we present the preliminary results of the VELAS device (MMO 980nm
      diode) in patients with chronic venous ulcer, associated with echo-guided
      polidocanol foam sclerotherapy for the treatment of varicosities. Primary
      outcomes were healing time of the venous ulcer, occlusion of the treated veins
      and treatment-related adverse events. We included 12 patients with insufficient
      saphenous vein and chronic venous ulcer. Initially, we treated all of them with
      thermoablation of the insufficient saphenous vein (VELAS), on an outpatient
      basis, with local anesthesia. After one week of the procedure, we sclerosed the
      varicosities with polidocanol foam (Tessari technique). The national VELAS device
      was easily handled. Total venous occlusion occurred in 83.3% of the patients (in
      seven days) and the association of the techniques was responsible for a wound
      healing rate of 83.3%, with no adverse events.

PMID- 28767809
TI  - Social policy and health policy in Latin America: a field of political struggle.

PMID- 28767810
TI  - The Welfare State in Latin America: reform, innovation and fatigue.
AB  - This paper analyses the challenges of building the Welfare State in late
      democracies in Latin America. The author shows how the literature has identified
      different social protection patterns in the region and how recent reform models
      have transformed institutions, in an unfavorable socioeconomic context. The
      results point to the emergence of a mixture of social protection measures that
      have increased coverage and reduced poverty, but are unable to guarantee
      universal citizens' rights and longevity.

PMID- 28767811
TI  - Health policies and systems in Latin America: regional identity and national
      singularities.

PMID- 28767812
TI  - [A health system's neoliberal reform: evidence from the Mexican case].
AB  - This study addressed the shaping of Mexico's health system in recent years, with
      an analysis of the social determination conditioning the system's current
      formulation, the consequences for the population's living and working conditions,
      and the technical and legal reform measures that shaped the system's
      transformation. The article then analyzes the survival of social security
      institutions and the introduction of an individual insurance model and its
      current implications and consequences. From the perspective of the right to
      health, the article compares the measures, resources, and interventions in both
      health care models and highlights the relevance of the social security system for
      Popular Insurance. The article concludes that the measures implemented to reform
      the Mexican health system have failed to achieve the intended results; on the
      contrary, they have led to a reduction in interventions, rising costs, and a
      decrease in the installed capacity and professional personnel for the system's
      operation, thus falling far short of solving the problem, rather aggravating the
      inequities without solving the system's structural contradictions. Health systems
      face new challenges, inevitably requiring that the analyses be situated in a
      broader framework rather than merely focusing on the functional, administrative,
      and financial operation of the systems in the respective countries.

PMID- 28767813
TI  - [New changes, old systems: health policies in Mexico and Colombia in the 21st
      century].
AB  - Recent years have witnessed discussion on the need for changes in the health
      systems of Latin America. This initiative, spearheaded once again by the World
      Bank as Universal Health Coverage, focuses on strategies for protection against
      financial risks and unified access to essential services and medicines. Although
      the World Bank approaches have been incorporated in different ways by the
      region's countries since the 1980s, there have also been important breaks with
      this trend, for example in Argentina, Brazil, Uruguay, and Ecuador, which have
      sought at different times to implement policies and programs emphasizing non
      market-driven values. Nevertheless, recent political changes with the crisis of
      the so-called progressive governments have meant that the market-driven view of
      health has reappeared insistently on the public agendas. Middle-income countries
      like Mexico and Colombia have implemented changes based on this model, and in
      both cases different stakeholders have pushed the readjustment of the health
      systems towards the perspective of the international financial agencies. The
      current study contends that these changes, promoted as a "renewed" alternative to
      respond to the problems resulting from the transformations, conducted for
      slightly more than twenty years, actually maintain the basis of the neoliberal
      model for health care.

PMID- 28767814
TI  - [Public-private relations in the Colombian health system from 1991 to 2015].
AB  - The case of Colombia's health system exemplifies the neoliberal reforms conducted
      in Latin America, characterized by the private sector's broad participation in
      the administration of resources and provision of health services. The system
      includes a set of benefits for persons that can afford to pay and a package of
      basic services with state financing for poor persons. This study aimed to analyze
      the public-private arrangements in the Colombian health system from 1991 and
      2015, including the dimensions of insurance and financing. A case study was
      performed that included a literature review and analysis of documents and
      secondary data. The results suggest that the 1993 reform conceived of health as a
      public service to be provided by the market. There were changes in the state's
      role, delegating health care functions to the private sector through regulatory
      and contractual measures. Beginning in 2000, incremental reforms included
      instrumental changes in the system, while other initiatives aimed to expand the
      state's responsibilities in guaranteeing the right to health. In terms of health
      insurance, the main advances were the expansion of insurance coverage and
      harmonization of baskets of benefits between different insurance systems
      (although late). As for financing, there are important inequities in per capita
      spending between the different insurance systems and inefficiency in the
      financial intermediation. The Colombian case underscores the limits of
      structuring health systems with heavy market participation, and the study
      contributes to the debate on the challenges for social protection in health in
      Latin American countries.

PMID- 28767816
TI  - ?

PMID- 28767815
TI  - [Social protection in Latin America and the Caribbean: changes, contradictions,
      and limits].
AB  - Recent studies suggest that governments in the majority of Latin American and
      Caribbean countries were able to expand social investments and introduce
      innovations in social protection policies in the last two decades with positive
      results in the actions' coverage and impact. However, the restrictions imposed by
      the current fiscal crisis and the rise of governments more ideologically aligned
      with the neoliberal discourse in various countries in the region point to a new
      retreat of the state from the social area, thereby compromising recent advances.
      The article aims to discuss the changes, contradictions, and limits of recent
      social protection standards in Latin America and the Caribbean. The discussion
      includes three items: a description of the history of social protection in the
      region, seeking to identify its principal historical periods and characteristics
      (benefits, target public, and financing); the social protection models that have
      been implemented in the region; and the specific case of health. We argue that
      although countries have adopted different solutions in the field of social
      protection, the policies' hybrid nature (with extensive private sector
      participation in the financing, supply, and management of services) and the
      prevalence of segmented models (with differential access according to
      individuals' social status) have been predominant traits in social protection in
      Latin America and the Caribbean, thus limiting the possibilities for greater
      equity and social justice.

PMID- 28767817
TI  - ?

PMID- 28767818
TI  - [Minimal requeriments for the organization of the recovery room and nursing care
      due to its patients].
AB  - This article describes the minimal requeriments for the organization of a
      recovery room, focusing concept, environment, team work, selection of patients
      and their discharge, as well as the nursing care given to them.

PMID- 28767819
TI  - [Teaching of immunization in undergraduate nursing programs].
AB  - The teaching of immunization to undergraduate stands of the University of Sao
      Paulo School of Nursing is analysed. The problems found are reported and
      suggestions are made for improving it.

PMID- 28767820
TI  - [The children with burns admitted to a Pediatric Unit of a General Hospital].
AB  - The necessity of improving nursing care to children with burns, admitted to a
      Pediatric Unit of a General Hospital, led the authors to adapt the ward so as to
      have one room prepared for such children. Results were good. They can be proved
      by the quicker evolution of the patients' condition, the increased interest of
      nursing personnel in caring for such patients and in the decreasing time splent
      by them in the accomflish ment of their tashs.

PMID- 28767821
TI  - [Effects of the National System of Health on the health services offered to the
      people].
AB  - Analysis of the National System of Health in Brazil and of the health services
      offered to the people; of the possible effects of the former over the latter; and
      of the role of the nurse in this context.

PMID- 28767822
TI  - [Sole communication, a therapeutic manner of threating suffering children: report
      of an experience].
AB  - Aspects of the relationship and the communication of the author and a recently
      hospitalized child are analyzed.

PMID- 28767823
TI  - [The cibernetic sistem of mechanism of labour - pedagogical interpretation].
AB  - The authors, in this work destined to midwifery students, consider specially the
      phenomena of the mechanism of labour, from the point of view of its axiomatic
      interpretation.

PMID- 28767824
TI  - [Determination of blood pressure in children: conditions and procedures].
AB  - This study shows the conditions that should be considered to determine the
      arterial pressure in children by the auscultatory method. A standard method of
      choice of the suitable cuff for the child is reported and series of procedures
      that should be followed during the diastolic and sistolic pressure reading are
      related.

PMID- 28767825
TI  - ?

PMID- 28767826
TI  - [A study of sexual transmissible diseases in undergraduate students of an
      university in Sao Paulo].
AB  - This is a study about the sexual behaviour and venereal illnesses in
      undergraduate students of an university in Sao Paulo.

PMID- 28767827
TI  - [Utilization of two antisseptic techniques and two differents solutions of iodine
      alcohol in the skin preparation for abdominal surgery].
AB  - A comparative study of two antisseptic techniques used in the preparation of the
      skin for abdominal surgery , utilizing' two different solutions of iodine
      alcohol.

PMID- 28767828
TI  - ?

PMID- 28767829
TI  - [Bibliographic review of studies related with the different regions for
      application of intramuscular injections].
AB  - A survey was performed of the literature published until 1975 about intramuscular
      injections and the utilization of deltoid, dorsogluteal, ventrogluteal and
      lateral thigh regions for their administration; the different studies has been
      grouped by regions, and supported by these bibliographycal review, a chart was
      made with the most importants indications referring to each on of the regions for
      intramuscular injections.

PMID- 28767830
TI  - [Evaluation of conscious level in head-injury patients].
AB  - A study regarding the evaluation of conscious level in 50 patients with head
      injury, admitted in Neurosurgical Intensive Care Unit. For evaluation, the
      patient was observed and examined in his own bed, bee utilized a scale with three
      behaviors tables, a minimum score de 3 pointing the smaller degree of conscious
      level, and maximum score of 15 pointing the neurophysiologic normal state. The
      utilized method has demonstrated to be usefull for the precision facilities
      verified in evaluated answers and for the reduced time of appliance, which was
      around five minutes as a rule.

PMID- 28767831
TI  - [Profile of the brazilian nursing student].
AB  - Because the Author believes in the importance of keeping up to date information
      on demographic data, socio-economical origin, curriculum, present economic
      situation, request for scholar development, aspiration and information about
      carer expectation, that caracterize nursing students, and may furnish elements to
      improve programs and methods of clinical practice, this research was performed in
      1976 withe the sole objetive of obtaining these data. It is a descriptive - type
      of study and the data were collected through the application of a 39 - item -
      questionnaire applied to 150 (1973) and 300 (1976) third grade students of
      Nursing Schools of the State of Sao Paulo. Therefore the student profile that was
      obtained through this research shows emergency of correlated problems, that
      interfere directly on scholar efficiency. Trying to solve them within our nursing
      teaching boudaires seems to be more realistic. The way to try solving them
      requires from nursing educators efforts in order to search for and determine more
      adequate teaching methods and techniques. This task is of the utmost urgency in
      one has in mind the need of promoting efforts to increase students profits and a
      result of it, more efficient professionals in the future.

PMID- 28767832
TI  - [Psychological meaning of words related to health by faculties of psychology and
      nursing schools].
AB  - Faculty's answers to the D. S. were studied, in order to relate them to common
      and especial educational goals as to the difference and similarities observed.
      Next, a "Student's t" statistical analysis and analysis of variances of the data
      was performed, which confirmed results of a prior study on groupal contingencies
      controlling affective meaning of words relating to health. However, the criterion
      adopted to establish sub-groups was not sufficiently differenciating.

PMID- 28767833
TI  - ?

PMID- 28767834
TI  - [Some aspects of teaching-service integration].
AB  - This article analyzes the situation of the nursing educator and the three roles
      she should carry out: teaching, nursing service and research. Besides these roles
      are those she should carry out as human being in a social context. The internal
      and external motivation and the conflicts and feelings that cause an educator to
      avoid carrying out some of these roles are analyzed. No answer is given for the
      questions raised; however, it is suggested that an intense, humble study of
      experience, with self analysis, would help the nursing educator to be more
      realistic and to come to an equilibrium.

PMID- 28767835
TI  - [Vomiting and hematemesis: generals aspects and nursing care].
AB  - The authors describe succintly concept, physiopathology and most common causes of
      vomiting and hematemesis and the needed nursing care when such conditions are
      present.

PMID- 28767836
TI  - [Theoretical aspects of the primary health care].
AB  - The author presents a article of the foundations of primary health care. She
      refers to some international and national meetings that recommend the extension
      of health care to the whole population; she also designs the new proposal for
      reorganization and extension of the Health Service System and describes some
      operative strategies to accomplish such extension.

PMID- 28767837
TI  - [Sterilization control. Role of the nurse].
AB  - The author describes methods and techniques of sterilization control and
      emphatizes its importance in the control of infection.

PMID- 28767838
TI  - [How perceived inefficiency in the teaching of Pediatric Nursing, in relation to
      the assistance given to parents].
AB  - The possible causes for the student's resistance in regard to the realization of
      certain tasks in the discipline of Pediatric Nursing are focalized and analysed.

PMID- 28767839
TI  - [Family Planning - "Billings" ovulation method].
AB  - The authors present "Billing" ovulation method as natural family planning.

PMID- 28767840
TI  - [Nursing care to senile patients].
AB  - The authors consider senescence and senility and discuss nursing care to senile
      patients.

PMID- 28767841
TI  - [The work of a volunteer nurse].
AB  - The author describes her activities as volunteer in a pediatric health center
      belonging to a private non profit organization.

PMID- 28767842
TI  - [Pediatric nursing in intensive care unit, beyond technical activities].
AB  - This article is concerned with nursing's aspects to be observed in assistance of
      children in Intensive Care Units, emphasizing the child's emotional care and the
      nurse-child relationship.

PMID- 28767843
TI  - [Male nursing students: a problem for the teaching of Obstetrical Nursing?]
AB  - The author presents a revision of the literature on the teaching of Obstetrical
      Nursing to male nursing students and describes the teaching of this subject at
      the University of Sao Paulo School of Nursing.

PMID- 28767844
TI  - [Tool and procedures for research in psychiatric nursing. I - Classification of
      the activities performed by nursing personnel].
AB  - This is a study of the activities of nursing personnel in psychiatric hospitals,
      in which the observation method was employed.

PMID- 28767845
TI  - [Tool and procedures for research in psychiatric nursing. II - Inventory of
      possible situations in psychiatric nursing].
AB  - The author lists situations in which psychiatric patients' basic needs are
      affected and possible activities of the nursing personnel to meet them.

PMID- 28767846
TI  - [Prevention of tuberculosis in pregnant women at the health services of Sao Paulo
      city].

PMID- 28767847
TI  - [Systematic observation of nursing team's procedures in urine collect to
      culture].
AB  - The objective of this paper is to study the quality of procedures utilized by
      nursing team in urine collect to culture in hospitals and laboratories of Sao
      Paulo City.

PMID- 28767848
TI  - ?

PMID- 28767849
TI  - ?

PMID- 28767850
TI  - ?

PMID- 28767851
TI  - ?

PMID- 28767852
TI  - [Importance of the communication process for nursing practice].
AB  - The Author presents a survey of the literature about the importance of
      communication in the nursing-patient interaction regardless to the area of
      practice. The author summarizes opinions about communication, therapeutic
      communication concepts and the need of nursing research in this area.

PMID- 28767854
TI  - [Basic aspects of the nursing care for the patients with South American Pemphigus
      Foliaceus].
AB  - The author analysis the problems of the South American Pemphigus Foliaceus, its
      epidemiology, diagnosis, treatment and prophilaxie. She presents the main needs
      of the patients with that disease and the basic aspects of the nursing care.

PMID- 28767853
TI  - [Vegetal medications of popular origin and its implications on the practice and
      teaching of nursing].
AB  - This paper discusses the popular use of medications of vegetas origin. The
      authors present the theoretical foundations of the subject, analyse the
      utilization of such medications and comment on its implications on the practice
      and teaching of nursing.

PMID- 28767855
TI  - [Learning the evaluation of the newborn's vitality by Apgar score].
AB  - The author describes the learning of the evaluation of the vitality of 43 newborn
      infants according to Apgar score by 16 nurse-midwifery students in a Sao Paulo
      Maternity Hospital.

PMID- 28767856
TI  - [Situation of teaching of venerai illness in Graduate Nursing School in Municipio
      de Sao Paulo].
AB  - This study has the objective to verify the situation of teaching of venerai
      illness in Graduate Nursing School, because of the vital importance of nurse
      participation in the control of venerai disease and in the health services.

PMID- 28767857
TI  - [Study about deficiencies in the psycho-social need fulfillment. Perception of
      the infectious hepatitis patients confined in Isolation Units].
AB  - Study about the dissatisfactions in the basic psychosocial needs fulfillment
      perceived by the contagious patients confined in Isolation Units.
      Dissatisfactions level is evaluated concerning to information, safety,
      consideration, self-actualization, autonomy and social needs. Results led to the
      conclusion that deficiencies level is high, mainly when the patients are new
      hospitalized and the fulfillment of those needs is perceived as very important by
      them.

PMID- 28767858
TI  - [Hospitalized child's behavior: a parameter to nursing assistence].
AB  - Report of the autohr's experience in Pediatric Nursing about a hospitalized child
      assistence, as a whole being, emphasizing child's emotional care and the author
      child relationship, based on the knowledge of affected necessities shown by
      child's behavior.

PMID- 28767860
TI  - ?

PMID- 28767859
TI  - [Informations given to contagious patient: comparative study between nurses and
      patients' opinion].

PMID- 28767861
TI  - [Factors influencing the freshmen in their professional choice of the "Escola de
      Enfermagem da Universidade de Sao Paulo": a research work].
AB  - The main objective of this study was to find out a some characteristics of the
      freshman of the Escola de Enfermagem da Universidade de Sao Paulo, in 1981, and
      verify which were the reasons that influenced their choice of nursing as a
      profession. Out of the 80 entering students, 51 answered the questionnaire; 47.0%
      indicated nursing as their first options; 60.8% of them had, in previous years,
      tried other schools. The answers more often given by these students for their
      choice of nursing as profession were related ta: interest in biological science,
      willing to help people and worry with level of well-being of the population.

PMID- 28767862
TI  - [Learning how to prepare the child to face difficult experiences].
AB  - This paper presents some considerations about the importance of nursing students
      learning to prepare children to face difficult situations. The author focuses on
      her experience as an instructor of undergraduate nursing students in a children's
      emergency room. She tells how she perceives the students and his learning
      experience in preparing children for these situations. She describes how
      facilitates this learning process for the student, by promoting an atmosphere of
      understanding, respect, trust and freedom to perceive, reflect and act.

PMID- 28767863
TI  - [Assistance to the woman in labor: some psychosocial aspects].
AB  - The woman in labor and the natural parturition process are considered within a
      psychosocial context, in order to provide for childbirth in hospital environment
      a aspect more humanized. Some aspects are pointed out as to influencing the
      hospital process and the behavior of the woman in labor, such as: hospital
      admission, emotional reactions and feelings relatives to labor and delivery and
      others.

PMID- 28767864
TI  - [Nurse-patient relationship].
AB  - The reason for the publication of this article is the author's concern with the
      quality of nursing assistance in psychiatric hospitals and the differences found
      among nursing schools in the teaching of psychiatric nursing to undergraduate
      students. She tried synthetize the basic knowledge needed for understanding the
      therapeutic nurse-patient relationship.

PMID- 28767865
TI  - [Evaluation of systematic orientation for speech rehabilitation on
      laryngectomized patients].
AB  - None of the surgeries performed today produces greater physiological and
      psychological changes than laryngectomy. After surgery, patients find themselves
      to be unable to speak, breathing through tracheotomy, with decreased smell and
      taste and most of the times suspecting they have cancer. The purpose of this work
      is to lest the method learning of esophageal speech intended to assist in
      rehabilitating laryngectomized patients. We have concluded that the method used
      to develop esophageal speech had satisfactory results; that the nurse has the
      skill required to guide this learning and to help laryngectomized patients with
      communication difficulties along with many others inherent to this condition.

PMID- 28767866
TI  - [Breastfeeding and relactation - nurse's intervention].
AB  - The role of the nurse both in breastfeeding and in relactation is presented
      according to Leavell's and Clark's levels of prevention. The authors describe the
      subject the mother should be taught during pregnancy and after delivery; they
      emphasize the preparation of the breasts for breastfeeding, the measures to be
      taken in periods of crisis and of hypogalactia, the procedures for promotion of
      relactation.

PMID- 28767868
TI  - [Territoriality of the hospitalized patient].

PMID- 28767867
TI  - [Nurse-patient relationship: account of an undergraduate nursing student].
AB  - This article is about nursing care given by a student nurse who emphasizes the
      impontance of Therapeutic Relationship process as a private action of the nurse.

PMID- 28767869
TI  - [Motorcycle accidents in Sao Paulo City, 1982].

PMID- 28767870
TI  - ?

PMID- 28767871
TI  - [Planning a nursing chart in the preoperative period].
AB  - The authors planned an instrument of communication which insure the
      individualized care to the patient in the perioperative period.

PMID- 28767872
TI  - [The philosophy of the nursing services of the University of Sao Paulo Hospital].
AB  - The authors offer suggestions for the philosophy to be adapted by the Nusing
      Division and Continued Education Service of the University of Sao Paulo Hospital.

PMID- 28767873
TI  - [Role of the nurse in the rehabilitation of handicapped children].
AB  - Role of the nurse in the rehabilitation of handicapped children. In the
      description of the role of the nurse in the rehabilitation of handicapped
      children, emphasis is given to the care.

PMID- 28767874
TI  - [The nursing in epidemiological vigilance].
AB  - In developing contries, transmissible diseases area a public health problem.
      According to the World Health Organization, increasing utilization of nurses in
      Epidemiological Vigilance actions is necessary. The author describes concepts,
      legislation and nursing activities in Great Sao Paulo, Brasil, in Epidemiological
      Vigilance.

PMID- 28767875
TI  - [Support as a therapeutic measure in the nurse patient relationship].
AB  - The authors make some theoretical considerations about support. They consider it
      one of the most efficient measures the nurse can use in her relationships with
      patient. They report the application of such measure in a process of student
      patient therapeutic relationships.

PMID- 28767876
TI  - [Antibiotics and chemotherapy nursing care].
AB  - The authors describe treatment by antibiotics and chemotherapy including the
      possible effects of drug association. They also emphasize the nursing care to be
      given to patients under treatment with such drugs.

PMID- 28767877
TI  - [How about more scientific writing and publishing? (A teaching strategy)].
AB  - From 1977 through 1980, in the S. PAULO UNIVERSITY NURSING SCHOOL, an alternative
      teaching strategy has been developed for use in the Licenciature Course for
      nurses (in which a practical approach is emphasized). An important part of that
      program consists in requesting from each of the students the engagement in an
      original research work and, subsequently, the writing of a paper on the subject.
      All the submitted papers are evaluated and the students are advised on any
      necessary improvements for future publication.

PMID- 28767878
TI  - [Nursing notes].
AB  - Aiming at some uniformity in nursing notes, the authors suggest a few norms on
      how to write them. This uniformity would help nursing students througout the
      whole nursing program.

PMID- 28767879
TI  - [The integration of Pediatric Nursing in basic course of Nursing School of Sao
      Paulo University].
AB  - The authors describe the development of the teaching of Pediatric Nursing at the
      University of Sao Paulo, School of Nursing, as well as the teachers' beliefs
      which determined the system of teaching in diferent chronological periods.

PMID- 28767880
TI  - [Nursing care of confused patients].
AB  - The authors give some basic ideas about confused patients and the nursing care
      reeded in such cases.

PMID- 28767881
TI  - [Tools and procedures for research in psychiatric nursing. III - Nursing
      personnels activities list and perceptions of their functions test].
AB  - Two instruments for investigation about psychiatric intervention are presented.
      One is about the attitude of nursing personnel towards the patient and the care
      he should receive. The other is described in a study armed at finding how this
      personnel see the nursing functions they performs.

PMID- 28767882
TI  - [The teaching of community nursing in Sao Paulo, Brasil].
AB  - This study offer basis for the establishment of community nursing models for the
      state of Sao Paulo, Brazil.

PMID- 28767883
TI  - Blood Pressure Targets: Will We Reach Definite Figures? I Currently Have Mine.

PMID- 28767884
TI  - Case 3/2017 - A 47-Year-Old Female with Refractory Heart Failure and Embolic
      Acute Myocardial Infarction.

PMID- 28767885
TI  - Symptomatic Exercise-induced Intraventricular Gradient in Competitive Athlete.

PMID- 28767886
TI  - Angiosarcoma Arising from the Main Pulmonary Artery Mimicking Pulmonary
      Thromboembolism.

PMID- 28767887
TI  - Clusia criuva Cambess. (Clusiaceae): anatomical characterization, chemical
      prospecting and antioxidant activity.
AB  - This study aims the anatomical description and chemical characterization of
      aerial parts of Clusia criuva Cambess., Clusiaceae in addition to the evaluation
      of the antioxidant activity of crude extracts, correlated to the flavonoid
      content. The morphological characterization was performed using traditional
      techniques of plant anatomy. For phytochemical studies, crude extracts were
      obtained by static maceration and analyzed by thin layer chromatography. The
      antioxidant activity and the flavonoids content were determined by colorimetric
      methods involving, respectively, 2,2-diphenyl-1-picrylhydrazyl free radical and
      aluminum chloride. C. criuva has uniseriate epidermis, paracytic stomata,
      hypostomatic leaves, cuticular flanges and cordiform vascular cylinder with
      accessory bundles. Chemical prospecting confirmed the abundant presence of
      terpenes and phenols in the extracts of leaves and of fruits. The methanolic
      extract of seeds showed the lowest EC50 value, but the methanolic extract of
      pericarps exhibited the highest maximum antioxidant activity. The results
      suggested a high percentage of flavonoids in the hexanic extract of pericarps,
      however, this could represent, in fact, the presence of benzophenones. Secretory
      ducts and the shape of the midrib are diagnostic for C. criuva. The antioxidant
      activity is not directly related to the flavonoids. The results indicate the
      importance of future studies with C. criuva chemical constituents.

PMID- 28767888
TI  - Analog Models of Flanking Structures and a Natural Example in the Quadrilatero
      Ferrifero, Minas Gerais.
AB  - The aim of this study is to present analog models of flanking structures and to
      analyze the Fabrica Nova synform, Quadrilatero Ferrifero, Minas Gerais, from a
      geometric point of view. We set up seven models using a linear viscous silicone
      and produced flanking structures with a shear velocity of 2 cm h-1. At different
      initial orientations with respect to the shear zone boundary, a rigid cross
      cutting element with lubricated boundaries was deformed via sinistral bulk flow
      at a shear strain of gamma = 1.28. The most interesting features of our
      experiments are the geometries of the different marker lines, which are
      heterogeneous and resulted from thickening and thinning of the silicone at the
      cross-cutting element terminations. To compare our analog models and the Fabrica
      Nova synform, we analyzed the outermost marker line of the analog models and the
      top surface of the Caue Formation in the Paleoproterozoic metasediments. The best
      comparisons between the experiments and the natural example were obtained by our
      CIS90 model in terms of the flexure shape near the cross-cutting element and the
      cross-cutting element orientation. Thus, we suggest that the cross-cutting
      elements in both situations act as obstacles and consequently produce local
      perturbations in laminar flow.

PMID- 28767889
TI  - Activity of Brazilian propolis against Aeromonas hydrophila and its effect on
      Nile tilapia growth, hematological and non-specific immune response under
      bacterial infection.
AB  - The effect of the ethanolic extract of propolis (EEP) on Aeromonas hydrophila was
      analyzed by determination of minimum inhibitory concentration (MIC). Then, the
      effects of crude propolis powder (CPP) on growth, hemato-immune parameters of the
      Nile tilapia, as well as its effects on resistance to A. hydrophila challenge
      were investigated. The CPP (0.5, 1.0, 1.5, 2.0, 2.5 and 3.0%) was added to the
      diet of 280 Nile tilapia (50.0 +/- 5.7 g fish-1). Hemato-immune parameters were
      analyzed before and after the bacterial challenge. Red blood cell, hematocrit,
      hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin
      concentration (MCHC), and hydrogen peroxide (H2O2) and nitric oxide (NO) were
      evaluated. The MIC of the EEP was 13% (v/v) with a bactericidal effect after 24
      hours. Growth performance was significantly lower for those fish fed diets
      containing 2.5 and 3% of CPP compared to the control diet. Differences in CPP
      levels affected fish hemoglobin, neutrophils number and NO following the
      bacterial challenge. For others parameters no significant differences were
      observed. Our results show that although propolis has bactericidal properties in
      vitro, the addition of crude propolis powder to Nile tilapia extruded diets does
      not necessarily lead to an improvement of fish health.

PMID- 28767890
TI  - Chemical composition, antioxidant and antibacterial activities of essential oils
      from leaves and flowers of Eugenia klotzschiana Berg (Myrtaceae).
AB  - Many essential oils (EOs) of different plant species possess interesting
      antimicrobial effects on buccal bacteria and antioxidant properties. Eugenia
      klotzschiana Berg (pera-do-cerrado, in Portuguese) is a species of Myrtaceae with
      restricted distribution in the Cerrado. The essential oils were extracted through
      the hydrodistillation technique using a modified Clevenger apparatus (2 hours)
      and chemically characterized by GC-MS. The major compounds were alpha-copaene
      (10.6 %) found in oil from leaves in natura, beta-bisabolene (17.4 %) in the
      essential oil from dry leaves and alpha-(E)-bergamotene (29.9 %) in oil from
      flowers. The antioxidant activity of essential oils showed similarities in both
      methods under analysis (DPPH and ABTS+) and the results suggested moderate to
      high antioxidant activity. The antibacterial activity was evaluated by
      determining minimum inhibitory concentrations (MICs), using the microdilution
      method. MIC values below 400 ug/mL were obtained against Streptococcus salivarius
      (200 ug/mL), S. mutans (50 ug/mL), S. mitis (200 ug/mL) and Prevotella nigrescens
      (50 ug/mL). This is the first report of the chemical composition and
      antibacterial and antioxidant activities of the essential oils of E.
      klotzschiana. These results suggest that E. klotzschiana, a Brazilian plant,
      provide initial evidence of a new and alternative source of substances with
      medicinal interest.

PMID- 28767891
TI  - Morphophysiological and biochemical alterations in Ricinus communis L. seeds
      submitted to cobalt60 gamma radiation.
AB  - This study aimed to evaluate the radiosensitivity of castor bean seeds after
      applications of different doses of Cobalt60 gamma radiation. Seeds were pre
      soaked for 24 hours in distilled water and then irradiated with 50, 100, 150, and
      200 Gy, except the control. Sowing was performed in trays, which contained soil
      as substrate and were maintained in a greenhouse. The electrical conductivity,
      emergence, emergence speed index, growth parameters and activities of antioxidant
      enzymes (superoxide dismutase, ascorbate peroxidase, and catalase) were evaluated
      in the leaves and roots of castor bean seedlings. Gamma radiation did not affect
      the electrical conductivity of the seeds; however, at a dose of 200 Gy, the
      emergence and emergence speed index of the seedlings was negatively affected. An
      analysis of the morphophysiological parameters revealed a reduction in seedling
      size as the radiation dose increased. There was a significant increase in
      superoxide dismutase and ascorbate peroxidase activities at higher radiation
      doses in the leaves, but not in roots. Thus, the analysis of all the variables
      suggests a response pattern as to the morphophysiological and biochemical changes
      of castor bean seedlings due to the increase of gamma radiation, which may serve
      as a tool for generating greater genetic variability.

PMID- 28767892
TI  - Productive performance of Holstein calves finished in feedlot or pasture.
AB  - The use of animals from dairy farms is an alternative to meat production since it
      provides an increment of total income for farmers. This study aims to evaluate
      the performance of Holstein calves finished in two feeding systems (feedlot or
      pasture). Forty-three animals with 58 days old and 57 kg were divided in two
      treatments: 23 animals finished in feedlot with corn silage plus concentrate
      based on corn and soybean meal (40:60); 20 animals kept in cultivated pastures
      according to the period of the year: Italian ryegrass (Lolium multiflorum) and
      pearl millet (Pennisetum americanum) with supplementation with the same feedlot
      concentrate at 1% body weight. Animals were slaughtered with 200 kg. Dry matter
      and nutrient intake were determined, with the use of chromium oxide for
      estimating pasture intake. Feedlot animals had greater total intake and total
      digestible nutrients, resulting in higher average daily gain (0.949 vs 0.694 kg
      day-1). Crude protein intake, neutral detergent fiber and feed conversion did not
      show significant differences. Holstein calves have improved performance when
      finished in feedlot.

PMID- 28767893
TI  - Numerical Simulations to Assess ART and MART Performance for Ionospheric
      Tomography of Chapman Profiles.
AB  - The incomplete geometrical coverage of the Global Navigation Satellite System
      (GNSS) makes the ionospheric tomographic system an ill-conditioned problem for
      ionospheric imaging. In order to detect the principal limitations of the ill
      conditioned tomographic solutions, numerical simulations of the ionosphere are
      under constant investigation. In this paper, we show an investigation of the
      accuracy of Algebraic Reconstruction Technique (ART) and Multiplicative ART
      (MART) for performing tomographic reconstruction of Chapman profiles using a
      simulated optimum scenario of GNSS signals tracked by ground-based receivers.
      Chapman functions were used to represent the ionospheric morphology and a set of
      analyses was conducted to assess ART and MART performance for estimating the
      Total Electron Content (TEC) and parameters that describes the Chapman function.
      The results showed that MART performed better in the reconstruction of the
      electron density peak and ART gave a better representation for estimating TEC and
      the shape of the ionosphere. Since we used an optimum scenario of the GNSS
      signals, the analyses indicate the intrinsic problems that may occur with ART and
      MART to recover valuable information for many applications of Telecommunication,
      Spatial Geodesy and Space Weather.

PMID- 28767895
TI  - ?

PMID- 28767894
TI  - Comparative toxicity of essential oil and blends of selected terpenes of Ocotea
      species from Pernambuco, Brazil, against Tetranychus urticae Koch.
AB  - Essential oils from the leaves of two species of the genus Ocotea that occur in
      the Atlantic Forest in the state of Pernambuco, Brazil, were analyzed using gas
      chromatography-mass spectrometry. The acaricidal activity of these oils as well
      as 11 selected components and blends were evaluated in fumigation and residual
      contact tests against the two-spotted spider mite (Tetranychus urticae). Sixty
      seven constituents were identified, totaling 97.3 +/- 0.3% and 97.8 +/- 0.5% of
      the oils from O. duckei and O. glomerata, respectively. Sesquiterpene was the
      dominant class. The compounds beta-caryophyllene (18.6 +/- 0.1%) and
      aromadendrene (17.3 +/- 0.6%) were the main constituents of the oils from O.
      duckei and O. glomerata, respectively. Acaricidal action varied depending on the
      method employed, species and chemical nature of the selected constituents. The
      mites were susceptible to the oils and chemical constituents using the fumigation
      method. The O. duckei oil was respectively 2.5-fold and 1.5-fold more toxic than
      the O. glomerata oil using the fumigation and residual contact methods. Among the
      selected constituents, beta-caryophyllene was the most toxic, independently of
      the method employed. The individual toxicity of the selected compounds and their
      blends as well as the role of these constituents in the overall toxicity of the
      essential oils are also discussed.

PMID- 28767896
TI  - [The utilization of the periodical in the library the University of Sao Paulo
      School of Nursing].
AB  - Selection, acquisition and space for storage of periodicals' collection, bring
      problems to the libraries. Considerations are made about the periodicals' titles
      acquired by buying, donation and exchange. Taking into consideration the great
      number of titles that already exist and the scarce budget, a study was made on
      the consulting of periodicals at the Library of the University Sao Paulo School
      of Nursing. Its objetives were: to identify the title of the most consulted
      periodicals in 1981; and the idiom in which they are published; how they were
      obteined. The findings, presented in Tables and Graphs, show that, as expected,
      the most consulted periodicals are the ones published in Portuguese, although
      they are in much lesser numbers. They also show a large number of consultations
      of the donated periodicals. The study includes a recommendation on the
      acquisition of periodicals.

PMID- 28767897
TI  - [Historical retrospective of nursing research in Brazil].
AB  - Types and lines of nursing research in Brazil, from 1950 to 1980, are described.
      The majority of studies are on nursing care, followed by nursing education. The
      Author concludes that probably these studies were an answer to the needs of the
      country.

PMID- 28767898
TI  - [The influence of nutrition on variation in length of estrous cycle in female
      rats].
AB  - The present studies were performed to determine the variation in length of the
      estrous cycle of undernourished female rats. The two groups studied received 4%
      and 8% protein diets, the first one group ad libitum and the second one
      controlled in quantity so that the animals of the two groups have the same growth
      rate.

PMID- 28767899
TI  - [The importance attributed to nursing intervention by nurses and geriatric
      patients].
AB  - The purpose of this study was to identify the degree of importance that nurses
      and geriatric patients attribute to nursing interventions in technical and
      expressive areas, as well as to compare the opinions obtained from the nurses and
      patients studied. The results indicated that geriatric patients attributed higher
      degree of importance to nursing interventions in the technical area than did the
      nurses. In the expressive area there was no significant difference between the
      two groups, except for the question about the company of relatives or friends
      during hospitalization.

PMID- 28767900
TI  - [Cognitive need of families of contagious patients hospitalized in Isolation
      Units. Preliminar study].
AB  - All the members of a contagious patient's family are affected by cognitive
      dissonance appeared consequently of infectious disease. Accurate information
      given by the nurse is fundamental to reduce anxiety of the patients' relatives.
      This study intends to verify mainly the need felt by the family on knowledge
      about disease, treatment, preventive measures, rules and regulations in.
      Isolation Units, working team and home care after discharge.

PMID- 28767901
TI  - [Manipulation behavior and therapeutic relationship].
AB  - The authors present a bibliographical review about concept and modalities of
      manipulative behavior and consider the importance of such manipulation in the
      therapeutic nurse-patient relationship. They emphasize the importance of the
      nurse being aware of about the occurence of this behavior, list some patient's
      manifestations and comment them, giving especial attention to the therapeutic
      measures to be taken.

PMID- 28767902
TI  - [Evolution of parenteral nutrition in the "Hospital da Beneficencia Portuguesa"].
AB  - The authors relate their experience about parenteral nutricional methods. They
      describe the systematization of nutrint solutions preparation and infection
      controls. Their results show the importance of the envolvement of nurses in the
      whole process of parenteral nutrition in the general hospital.

PMID- 28767903
TI  - [Health education in a Pediatric Out-Patient Clinic].
AB  - The Author reports some of her activities as a volunteer nurse in a Pediatric Out
      Patient Clinic operated by a non profit private institution. She describes the
      health education program for mothers on the introduction of soy bean in the menu.
      She also tells about the organization of a cash fund from which patients can
      borrow money to buy medication.

PMID- 28767904
TI  - [Nursing care in immunization programs].
AB  - The authors answer questions asked by nursing personnel, who work in teaching
      hospitals and in health centers, about immunization against measles and
      poliomyelitis, as well as questions about general care in other types of
      immunization. They recommend specific research on the subject.

PMID- 28767906
TI  - ?

PMID- 28767905
TI  - [What I learned interacting with orphan children].
AB  - The Author reports her experience with orphan children during her field work in
      an orphange as a nursing student, emphasizing some significant aspects for her
      learning. She concludes that there must be someone willing to receive all the
      love the orphan children have to give.

PMID- 28767907
TI  - Retinal changes in solid organ and bone marrow transplantation patients.
AB  - Objective: To evaluate retinal changes in patients who underwent solid organ or
      bone marrow transplantation. Methods: A retrospective analysis of medical records
      of patients evaluated from February 2009 to December 2016. All patients included
      underwent funduscopy. Clinical and demographic data regarding transplantation and
      ophthalmological changes were collected. Results: A total of 126 patients were
      analyzed; of these, 108 underwent transplantation and 18 were in the waiting
      list. Transplantation modalities were heart, lung, kidney, liver, pancreas,
      combined pancreas and kidney and bone marrow transplantation. The main pre
      transplantation comorbidities were diabetes and arterial hypertension. Of the 108
      transplanted patients, 82 (76%) had retinal changes. All patients who underwent
      pancreas or combined pancreas and kidney transplantation had diabetic
      retinopathy. The main retinal changes found were diabetic retinopathy,
      hypertensive retinopathy, retinal vascular occlusions, chorioretinal infections
      and central serous chorioretinopathy. Conclusion: Retinal changes were either
      related to preexisting conditions, mainly diabetic retinopathy, or developed
      postoperatively as a complication of the surgical procedure, or as an infection
      related to the immunosuppressive status, or due to drug toxicity. These patients
      may present with complex ophthalmological changes and should be carefully
      evaluated prior to surgery and further followed by an ophthalmologist skilled in
      the management of diabetic retinopathy and posterior pole infections. Objetivo:
      Analisar as alteracoes retinianas de pacientes submetidos a transplantes de
      orgaos solidos ou de medula ossea. Metodos: Analise de prontuario dos pacientes
      avaliados no periodo de fevereiro de 2009 a dezembro de 2016. Todos os pacientes
      incluidos foram submetidos a avaliacao fundoscopica. Foram coletados dados
      demograficos e clinicos, referentes ao transplante e as alteracoes oftalmologicas
      encontradas. Resultados: Foram avaliados 126 pacientes, sendo 108 submetidos a
      transplantes e 18 que aguardavam o procedimento. Foram avaliados pacientes
      submetidos a transplantes de coracao, pulmao, rim, figado, pancreas, pancreas-rim
      e medula ossea. As principais comorbidades pre-transplante foram diabetes e
      hipertensao arterial. Dos 108 pacientes transplantados, 82 (76%) apresentaram
      alteracoes retinianas. Todos os pacientes submetidos ao transplante de pancreas
      ou pancreas-rim apresentaram alteracoes retinianas relacionadas ao diabetes. As
      principais alteracoes retinianas detectadas foram retinopatia diabetica,
      retinopatia hipertensiva, oclusoes vasculares retinianas, infeccoes
      coriorretinianas e coriorretinopatia serosa central. Conclusao: As alteracoes
      retinianas estavam relacionadas a doencas preexistentes, principalmente a
      retinopatia diabetica, ou surgiram apos o transplante, como complicacao do
      procedimento cirurgico, ou como complicacao infecciosa associada a
      imunossupressao, ou ainda por toxicidade medicamentosa. Tais pacientes podem
      apresentar alteracoes oculares complexas, devendo ser submetidos a avaliacao
      retiniana pre-operatoria cuidadosa e ao acompanhamento pos-operatorio por
      oftalmologista especializado no manejo da retinopatia diabetica e de doencas
      infecciosas do segmento posterior ocular.

PMID- 28767908
TI  - Work addiction and quality of life: a study with physicians.
AB  - Objective: To evaluate the quality of life of physicians and investigate to what
      extent it is affected by work addiction. Methods: This is an exploratory,
      descriptive and cross-sectional study, conducted with 1,110 physicians. For data
      collection, we used a questionnaire with sociodemographic information, the World
      Health Organization Quality of Life BREF, and the Work Addiction Scale. Results:
      Most physicians presented high quality of life. Female participants presented
      lower quality of life in the domains psychologic, environment and general
      (p<0.05). Quality of life was negatively correlated with the number of shifts
      (p<0.005). The higher the addiction to work, the lower the quality of life.
      Conclusion: The research allowed understanding the implications of work addiction
      in the quality of life. Further studies are required to support the development
      of strategies that improve health conditions and quality of life of medical
      professionals. Objetivo: Avaliar a qualidade de vida de medicos e investigar em
      que medida a adicao ao trabalho a afeta. Metodos: Trata-se de um estudo
      exploratorio, descritivo e transversal, realizado com 1.110 medicos. Para coleta
      de dados, optou-se por utilizar um questionario contendo informacoes
      sociodemograficas, bem como aplicar o instrumento World Health Organization
      Quality of Life-BREF e a Escala de Adicao ao Trabalho. Resultados: Os medicos, em
      sua maioria, apresentaram alta qualidade de vida. Os participantes do sexo
      feminino tiveram menor qualidade de vida em relacao aos homens nos dominios
      psicologico, meio ambiente e geral (p<0,05). A qualidade de vida correlacionou-se
      negativamente com o numero de plantoes (p<0,005), e quanto maior a adicao ao
      trabalho, menor a qualidade de vida. Conclusao: A pesquisa permitiu o
      conhecimento das implicacoes da adicao ao trabalho sobre a qualidade de vida.
      Novos estudos sao necessarios para subsidiar a elaboracao de estrategias que
      melhorem a saude e a qualidade de vida do profissional medico.

PMID- 28767909
TI  - Association of subclinical inflammation, glycated hemoglobin and risk for
      obstructive sleep apnea syndrome.
AB  - Objective: To investigate the inter-relation between high sensitivity C-reactive
      protein and glycated hemoglobin in prediction of risk of obstructive sleep apnea.
      Methods: We included all individuals participating in a check-up program at the
      Preventive Medicine Center of Hospital Israelita Albert Einstein in 2014. The
      Berlin questionnaire for risk of obstructive sleep apnea was used, and the high
      sensitivity C-reactive protein and glycated hemoglobin levels were evaluated.
      Results: The sample included 7,115 participants (age 43.4+/-9.6 years, 24.4%
      women). The Berlin questionnaire showed changes in 434 (6.1%) individuals. This
      finding was associated with high sensitivity C-reactive protein and glycated
      hemoglobin levels (p<0.001). However, only the association between the Berlin
      questionnaire result and glycated hemoglobin remained significant in the adjusted
      multivariate analysis, for the traditional risk factors and for an additional
      model, including high-density lipoprotein cholesterol and triglycerides.
      Conclusion: The glycated hemoglobin, even below the threshold for diagnosis of
      diabetes, is independently associated with obstructive sleep apnea syndrome, even
      after adjustment for obesity and C-reactive protein. These findings suggest a
      possible pathophysiological link between changes in insulin resistance and
      obstructive sleep apnea syndrome, independently from obesity or low-grade
      inflammation. Objetivo: Investigar a inter-relacao entre proteina C-reativa de
      alta sensibilidade e hemoglobina glicada na predicao do risco de apneia
      obstrutiva do sono. Metodos: Foram incluidos todos os individuos participantes do
      programa de check-up do Centro de Medicina Preventiva Hospital Israelita Albert
      Einstein em 2014. Foi aplicado o questionario de Berlin sobre risco de apneia do
      sono, e avaliadas as dosagens de hemoglobina glicada e proteina C-reativa de alta
      sensibilidade. Resultados: Foram incluidos 7.115 participantes (idade 43,4+/-9,6
      anos, 24,4% mulheres). A prevalencia de alteracao no questionario de Berlin foi
      de 434 (6,1%). A alteracao do questionario de Berlin associou-se positivamente
      aos resultados da proteina C-reativa de alta sensibilidade e da hemoglobina
      glicada (p<0,001). No entanto, apenas a associacao entre o resultado do
      questionario de Berlin e a hemoglobina glicada permaneceu significativa na
      analise multivariada ajustada tanto para fatores de risco tradicionais quanto
      para um modelo adicional, que incluiu tambem lipoproteina de alta densidade
      colesterol (HDL-c) e triglicerides. Conclusao: A hemoglobina glicada, mesmo em
      valores abaixo do criterio diagnostico para diabetes mellitus, esta associada de
      forma independente ao risco para sindrome da apneia obstrutiva do sono, mesmo
      apos ajuste para obesidade e proteina C-reativa. Estes achados sugerem possivel
      ligacao fisiopatologica entre alteracoes na resistencia insulinica e a sindrome
      da apneia obstrutiva do sono, que independe da obesidade ou inflamacao de baixo
      grau.

PMID- 28767910
TI  - Heart rate variability based on risk stratification for type 2 diabetes mellitus.
AB  - Objective: To evaluate heart rate variability among adults with different risk
      levels for type 2 diabetes mellitus. Methods: The risk for type 2 diabetes
      mellitus was assessed in 130 participants (89 females) based on the questionnaire
      Finnish Diabetes Risk Score and was classified as low risk (n=26), slightly
      elevated risk (n=41), moderate risk (n=27) and high risk (n=32). To measure heart
      rate variability, a heart-rate monitor Polar S810i(r) was employed to obtain RR
      series for each individual, at rest, for 5 minutes, followed by analysis of
      linear and nonlinear indexes. Results: The groups at higher risk of type 2
      diabetes mellitus had significantly lower linear and nonlinear heart rate
      variability indexes. Conclusion: The individuals at high risk for type 2 diabetes
      mellitus have lower heart rate variability. Objetivo: Avaliar a variabilidade da
      frequencia cardiaca em adultos com diferentes niveis de risco para diabetes
      mellitus tipo 2. Metodos: O grau de risco para diabetes mellitus tipo 2 de 130
      participantes (41 homens) foi avaliado pelo questionario Finnish Diabetes Risk
      Score. Os participantes foram classificados em baixo risco (n=26), risco
      levemente elevado (n=41), risco moderado (n=27) e alto risco (n=32). Para medir a
      variabilidade da frequencia cardiaca, utilizou-se o frequencimetro Polar S810i(r)
      para obter series de intervalo RR para cada individuo, em repouso, durante 5
      minutos; posteriormente, realizou-se analise por meio de indices lineares e nao
      lineares. Resultados: O grupo com maior risco para diabetes mellitus tipo 2 teve
      uma diminuicao significante nos indices lineares e nao-lineares da variabilidade
      da frequencia cardiaca. Conclusao: Os resultados apontam que individuos com risco
      alto para diabetes mellitus tipo 2 tem menor variabilidade da frequencia
      cardiaca. Objective: To evaluate heart rate variability among adults with
      different risk levels for type 2 diabetes mellitus. Methods: The risk for type 2
      diabetes mellitus was assessed in 130 participants (89 females) based on the
      questionnaire Finnish Diabetes Risk Score and was classified as low risk (n=26),
      slightly elevated risk (n=41), moderate risk (n=27) and high risk (n=32). To
      measure heart rate variability, a heart-rate monitor Polar S810i(r) was employed
      to obtain RR series for each individual, at rest, for 5 minutes, followed by
      analysis of linear and nonlinear indexes. Results: The groups at higher risk of
      type 2 diabetes mellitus had significantly lower linear and nonlinear heart rate
      variability indexes. Conclusion: The individuals at high risk for type 2 diabetes
      mellitus have lower heart rate variability.

PMID- 28767911
TI  - Test-retest reliability of Brazilian version of Memorial Symptom Assessment Scale
      for assessing symptoms in cancer patients.
AB  - Objective: To assess the test-retest reliability of the Memorial Symptom
      Assessment Scale translated and culturally adapted into Brazilian Portuguese.
      Methods: The scale was applied in an interview format for 190 patients with
      various cancers type hospitalized in clinical and surgical sectors of the
      Instituto Nacional de Cancer Jose de Alencar Gomes da Silva and reapplied in 58
      patients. Data from the test-retest were double typed into a Microsoft Excel
      spreadsheet and analyzed by the weighted Kappa. Results: The reliability of the
      scale was satisfactory in test-retest. The weighted Kappa values obtained for
      each scale item had to be adequate, the largest item was 0.96 and the lowest was
      0.69. The Kappa subscale was also evaluated and values were 0.84 for high
      frequency physic symptoms, 0.81 for low frequency physical symptoms, 0.81 for
      psychological symptoms, and 0.78 for Global Distress Index. Conclusion: High
      level of reliability estimated suggests that the process of measurement of
      Memorial Symptom Assessment Scale aspects was adequate. Objetivo: Avaliar a
      confiabilidade teste-reteste da versao traduzida e adaptada culturalmente para o
      portugues do Brasil do Memorial Symptom Assessment Scale. Metodos: A escala foi
      aplicada em forma de entrevista em 190 pacientes com diversos tipos de cancer
      internados nos setores clinicos e cirurgicos do Instituto Nacional de Cancer Jose
      de Alencar Gomes da Silva e reaplicada em 58 pacientes. Os dados dos testes
      retestes foram inseridos num banco de dados por dupla digitacao independente em
      Excel e analisados pelo Kappa ponderado. Resultados: A confiabilidade da escala
      mostrou-se satisfatoria nos testes-retestes. Os valores do Kappa ponderado
      obtidos para cada item da escala apresentaram-se adequados, sendo o maior item de
      0,96 e o menor de 0,69. Tambem se avaliou o Kappa das subescalas, sendo de 0,84
      para sintomas fisicos de alta frequencia, de 0,81 para sintomas fisicos de baixa
      frequencia, de 0,81 tambem para sintomas psicologicos, e de 0,78 para Indice
      Geral de Sofrimento. Conclusao: Altos niveis de confiabilidade estimados permitem
      concluir que o processo de afericao dos itens do Memorial Symptom Assessment
      Scale foi adequado.

PMID- 28767912
TI  - Translation and cultural adaptation of the Functional Assessment of Chronic
      Illness Therapy - Cervical Dysplasia (FACIT-CD) to evaluate quality of life in
      women with cervical intraepithelial neoplasia.
AB  - Objective: To translate and perform the cultural adaptation of the tool
      Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD)
      to the Portuguese language. Methods: A descriptive cross-sectional study, with
      translation and cultural adaptation of the assessment tool performed according to
      international guidelines and the Functional Assessment of Chronic Illness Therapy
      (FACIT) protocol group. It involved eight experts, six from Brazil, one from
      Portugal and one from the United States. After translation and back-translation
      of the tool, the semantic analysis process was carried out. We randomly included
      20 women aged between 18 and 70 years with altered cervical cytology exam, seen
      at the Department of Prevention and Gynecologic Oncology - Hospital de Cancer de
      Barretos. Results: The sample consisted of women with low education level. In the
      first pre-test, ten women participated and half of them considered the questions
      CD1, CD2 and CD3 as difficult, because they did not understand the meaning of the
      term "pelvic area". The question CD5, "I worry about spreading the infection",
      was also considered difficult to understand by five women. After the
      reconsideration of the expert committee and FACIT group, the second pre-test was
      performed. At this stage, we concluded that the previously raised understanding
      problems had been solved. Conclusion: The translated version of FACIT-CD in
      universal Portuguese language is equivalent to the original version in English
      and was easily understood by patients with cervical intraepithelial neoplasia.
      Objetivo: Traduzir e adaptar o instrumento Functional Assessment of Chronic
      Illness Therapy - Cervical Dysplasia (FACIT-CD), para a lingua portuguesa.
      Metodos: Estudo descritivo, transversal, com metodologia de traducao e adaptacao
      cultural de instrumento de avaliacao, realizado por meio de diretrizes
      internacionais e seguindo o protocolo do grupo Functional Assessment of Chronic
      Illness Therapy (FACIT). Envolveu oito especialistas, sendo seis nativos do
      Brasil, um de Portugal e um dos Estados Unidos. Ao termino do processo de
      traducao e retrotraducao, deu-se inicio ao processo de analise semantica. Foram
      incluidas aleatoriamente 20 mulheres entre 18 e 70 anos com exame de citologia
      cervical alterado, atendidas no Departamento de Prevencao e Ginecologia
      Oncologica do Hospital de Cancer de Barretos. Resultados: A amostra foi composta
      por mulheres com baixa escolaridade. No primeiro pre-teste participaram dez
      mulheres, sendo que a metade considerou as questoes CD1, CD2 e CD3 dificeis por
      nao compreenderem o significado do termo "regiao pelvica". A questao CD5, "Estou
      preocupada em disseminar a infeccao", tambem foi considerada de dificil
      entendimento por cinco mulheres. Apos as reconsideracoes do comite de
      especialistas e do grupo FACIT, foi realizado o segundo pre-teste. Nesta fase,
      pode-se concluir que os problemas de entendimento anteriores foram resolvidos.
      Conclusao: A versao traduzida do FACIT-CD e equivalente a versao original em
      ingles e em lingua portuguesa universal, sendo facilmente compreendida pelas
      pacientes com neoplasia intraepitelial cervical.

PMID- 28767913
TI  - Spontaneous breathing test in the prediction of extubation failure in the
      pediatric population.
AB  - Objective: To assess whether the spontaneous breathing test can predict the
      extubation failure in pediatric population. Methods: A prospective and
      observational study that evaluated data of inpatients at the Pediatric Intensive
      Care Unit between May 2011 and August 2013, receiving mechanical ventilation for
      at least 24 hours followed by extubation. The patients were classified in two
      groups: Test Group, with patients extubated after spontaneous breathing test, and
      Control Group, with patients extubated without spontaneous breathing test.
      Results: A total of 95 children were enrolled in the study, 71 in the Test Group
      and 24 in the Control Group. A direct comparison was made between the two groups
      regarding sex, age, mechanical ventilation time, indication to start mechanical
      ventilation and respiratory parameters before extubation in the Control Group,
      and before the spontaneous breathing test in the Test Group. There was no
      difference between the parameters evaluated. According to the analysis of
      probability of extubation failure between the two groups, the likelihood of
      extubation failure in the Control Group was 1,412 higher than in the Test Group,
      nevertheless, this range did not reach significance (p=0.706). This model was
      considered well-adjusted according to the Hosmer-Lemeshow test (p=0.758).
      Conclusion: The spontaneous breathing test was not able to predict the extubation
      failure in pediatric population. Objetivo: Avaliar se o teste de respiracao
      espontanea pode ser utilizado para predizer falha da extubacao na populacao
      pediatrica. Metodos: Estudo prospectivo, observacional, no qual foram avaliados
      todos os pacientes internados no Centro de Terapia Intensiva Pediatrica, no
      periodo de maio de 2011 a agosto de 2013, que utilizaram ventilacao mecanica por
      mais de 24 horas e que foram extubados. Os pacientes foram classificados em dois
      grupos: Grupo Teste, que incluiu os pacientes extubados depois do teste de
      respiracao espontanea; e Grupo Controle, pacientes foram sem teste de respiracao
      espontanea. Resultados: Dos 95 pacientes incluidos no estudo, 71 criancas eram do
      Grupo Teste e 24 eram do Grupo Controle. Os grupos foram comparados em relacao a:
      sexo, idade, tempo de ventilacao mecanica, indicacao para inicio da ventilacao
      mecanica e parametros ventilatorios pre-extubacao, no Grupo Controle, e pre
      realizacao do teste, no Grupo Teste. Nao foram observadas diferencas entre os
      parametros analisados. Em relacao a analise da probabilidade de falha da
      extubacao entre os dois grupos de estudo, a chance de falha do Grupo Controle foi
      1.412 maior do que a das criancas do Grupo Teste, porem este acrescimo nao foi
      significativo (p=0,706). O modelo foi considerado bem ajustado de acordo com o
      teste de Hosmer-Lemeshow (p=0,758). Conclusao: O teste de respiracao espontanea
      para a populacao pediatrica nao foi capaz de prever a falha da extubacao.

PMID- 28767914
TI  - Comparison of enterovirus detection in cerebrospinal fluid with Bacterial
      Meningitis Score in children.
AB  - Objective: To measure the role of enterovirus detection in cerebrospinal fluid
      compared with the Bacterial Meningitis Score in children with meningitis.
      Methods: A retrospective cohort based on analysis of medical records of pediatric
      patients diagnosed as meningitis, seen at a private and tertiary hospital in Sao
      Paulo, Brazil, between 2011 and 2014. Excluded were patients with critical
      illness, purpura, ventricular shunt or recent neurosurgery, immunosuppression,
      concomitant bacterial infection requiring parenteral antibiotic therapy, and
      those who received antibiotics 72 hours before lumbar puncture. Results: The
      study included 503 patients. Sixty-four patients were excluded and 94 were not
      submitted to all tests for analysis. Of the remaining 345 patients, 7 were in the
      Bacterial Meningitis Group and 338 in the Aseptic Meningitis Group. There was no
      statistical difference between the groups. In the Bacterial Meningitis Score
      analysis, of the 338 patients with possible aseptic meningitis (negative
      cultures), 121 of them had one or more points in the Bacterial Meningitis Score,
      with sensitivity of 100%, specificity of 64.2%, and negative predictive value of
      100%. Of the 121 patients with positive Bacterial Meningitis Score, 71% (86
      patients) had a positive enterovirus detection in cerebrospinal fluid.
      Conclusion: Enterovirus detection in cerebrospinal fluid was effective to
      differentiate bacterial from viral meningitis. When the test was analyzed
      together with the Bacterial Meningitis Score, specificity was higher when
      compared to Bacterial Meningitis Score alone. Objetivo: Avaliar o papel da
      pesquisa de enterovirus no liquido cefalorraquidiano em comparacao com o Escore
      de Meningite Bacteriana em criancas com meningite. Metodos: Coorte retrospectiva,
      realizada pela analise de prontuarios, incluindo pacientes pediatricos, com
      diagnostico de meningite e atendidos em um hospital privado e terciario,
      localizado em Sao Paulo, entre 2011 e 2014. Foram excluidos os pacientes com
      doenca critica, purpura, derivacao ventricular ou neurocirurgia recente,
      imunossupressao, outra infeccao bacteriana concomitante que necessitasse de
      antibioticoterapia parenteral e aqueles que receberam antibiotico 72 horas antes
      da puncao lombar. Resultados: Foram incluidos no estudo 503 pacientes. Destes, 64
      foram excluidos e 94 nao realizaram todos os exames para analise. Dos 345
      pacientes restantes, 7 ficaram no Grupo de Meningite Bacteriana e 338 no Grupo de
      Meningite Asseptica. Nao houve diferenca estatistica entre os grupos. Na analise
      do Escore de Meningite Bacteriana, dos 338 pacientes com possivel meningite
      asseptica (culturas negativas), 121 deles tiveram um ou mais pontos para o Escore
      de Meningite Bacteriana, com valor de sensibilidade de 100%, especificidade de
      64,2% e valor preditivo negativo de 100%. Dos 121 pacientes com Escore de
      Meningite Bacteriana positivo, 71% (86 pacientes) tiveram a pesquisa de
      enterovirus positiva no liquido cefalorraquidiano. Conclusao: A pesquisa de
      enterovirus no liquido cefalorraquidiano mostrou-se eficaz em diferenciar a
      meningite bacteriana da viral. Analisada junto com o Escore de Meningite
      Bacteriana, a especificidade foi maior em comparacao ao Escore de Meningite
      Bacteriana isolado.

PMID- 28767915
TI  - Evaluation of periodontal condition and risk in patients with chronic kidney
      disease on hemodialysis.
AB  - Objective: To establish a profile of periodontal conditions in chronic kidney
      disease patients on hemodialysis and their periodontal risk. Methods: We included
      115 patients on hemodialysis. Clinical periodontal parameters assessed were:
      plaque index, gingival index, probing depth and clinical attachment level.
      Patients were classified according to presence/absence and severity of
      periodontal disease and periodontal risk. Results: In 107 dentate patients (93%)
      the plaque index was 1.53+/-0.78, the gingival index was 0.95+/-0.85, the probing
      depth was 2.2+/-0.6mm and the clinical attachment level was 3.18+/-1.75mm. We
      observed that 1 patient (0.94%) did not have periodontal disease, 55 patients
      (51.40%) had slight, 28 (26.17%) moderate and 23 (21.49%) severe periodontal
      disease. Among 107 patients, 37 (34.58%) had low risk, 35 (32.71%) moderate risk
      and 35 (32.71%) high risk. Patients with severe periodontal disease showed 104.5
      more chance of high risk compared with low risk individuals (odds ratio: 104.5;
      95%CI: 10.7-1017.2; p<0.0001). Conclusion: Most of patients with chronic renal
      disease presented periodontal disease, indicating the presence of chronic
      inflammatory and infection process that may influence in systemic conditions. A
      prevention and interventionist approach in this population is needed, especially
      to emphasize the importance of oral health. The periodontal risk assessment is a
      useful tool to create individualized periodontal therapies and to improve general
      health condition. Objetivo: Tracar um perfil das condicoes periodontais de
      pacientes com doenca renal cronica em hemodialise e seu risco periodontal.
      Metodos: Foram incluidos no estudo 115 pacientes em hemodialise. Os parametros
      clinicos periodontais avaliados foram: indice de placa, indice gengival,
      profundidade de sondagem e perda de nivel de insercao clinico. Os pacientes foram
      classificados de acordo com a presenca e a gravidade da doenca periodontal, bem
      como de acordo com o risco periodontal. Resultados: Quanto aos parametros
      clinicos, 107 pacientes dentados (93%) apresentaram media de indice de placa de
      1,53+/-0,78 e gengival de 0,95+/-0,85, profundidade de sondagem de 2,2+/-0,6mm e
      nivel de insercao clinica de 3,18+/-1,75mm. Em relacao a doenca periodontal, 1
      (0,94%) era saudavel, 55 (51,40%) apresentavam periodontite leve, 28 (26,17%)
      moderada e 23 (21,49%) avancada. Com relacao ao risco, dos 107 pacientes, 37
      apresentavam risco baixo, 35 moderado e 35 alto. Os pacientes com doenca
      periodontal avancada apresentaram 104,5 vezes mais chance de ter alto risco
      comparado ao baixo (odds ratio: 104,5; IC95%: 10,7-1017,2; p<0,0001). Conclusao:
      A maioria dos pacientes com doenca renal cronica apresentou doenca periodontal,
      indicando um processo infeccioso e inflamatorio cronico, que pode influenciar na
      condicao sistemica. Evidencia-se a necessidade de uma abordagem preventiva e
      intervencionista nesta populacao, enfatizando a importancia da saude bucal. A
      avaliacao do risco periodontal seria uma ferramenta na elaboracao de terapias
      periodontais individualizadas para uma melhor condicao de saude geral.

PMID- 28767916
TI  - Transection of the hepatic parenchyma associated or not with the contralateral
      portal vein branch ligature and its effect in liver regeneration.
AB  - Objective: To analyze the influence of portal vein ligation in hepatic
      regeneration by immunohistochemical criteria. Methods: Ten pigs divided into two
      groups of five animals underwent hepatectomy in two stages, and the groups were
      differentiated by ligation or not of the left portal vein tributary, which is
      responsible for vascularization of the left lateral and medial lobes of the pig
      liver. Five days after the procedure, the animals underwent liver biopsies for
      further analysis of histological and immunohistochemical with marker Ki67.
      Results: The group submitted to hepatectomy with vascular ligation showed an
      increase of approximately 4% of hepatocytes in regeneration status, as well as a
      greater presence of Kupffer and inflammatory cells as compared to control.
      Conclusion: As a result of positive cell replication observed through the Ki67
      marker, we can suspect that the ligation of a tributary of the portal vein
      associated with liver resection promoted a greater stimulus of liver regeneration
      when compared to liver resection alone. Objetivo: Analisar a influencia da
      ligadura da tributaria da veia porta no estimulo regenerativo hepatico por meio
      de criterios imuno-histoquimicos. Metodos: Dez suinos, divididos em dois grupos
      de cinco animais, foram submetidos a hepatectomia em dois estagios, sendo que os
      grupos foram diferenciados pela ligadura ou nao da tributaria da veia porta,
      responsavel pela vascularizacao dos lobos lateral e medial esquerdos do figado do
      suino. Cinco dias apos o procedimento, os animais foram reabordados para retirada
      de amostras hepaticas para posterior analise de histologica e imunoistoquimica
      com o marcador Ki67. Resultados: O grupo submetido a hepatectomia com ligadura
      vascular apresentou incremento de 4% aproximadamente de hepatocitos em processo
      de regeneracao, bem como grande numero de celulas de Kupffer e celulas
      inflamatorias, quando comparado ao controle. Conclusao: Em virtude da analise
      positiva da replicacao celular observada por meio do marcador Ki67, pode-se
      observar que a ligadura de uma tributaria da veia porta promoveu um maior
      estimulo de regeneracao hepatica, efeito observado com menor intensidade no grupo
      submetido apenas a resseccao hepatica.

PMID- 28767917
TI  - Action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior
      and soleus muscles after nerve injury.
AB  - Objective: To evaluate the action of vanillin (Vanilla planifolia) on the
      morphology of tibialis anterior and soleus muscles after peripheral nerve injury.
      Methods: Wistar rats were divided into four groups, with seven animals each:
      Control Group, Vanillin Group, Injury Group, and Injury + Vanillin Group. The
      Injury Group and the Injury + Vanillin Group animals were submitted to nerve
      injury by compression of the sciatic nerve; the Vanillin Group and Injury +
      Vanillin Group, were treated daily with oral doses of vanillin (150mg/kg) from
      the 3rd to the 21st day after induction of nerve injury. At the end of the
      experiment, the tibialis anterior and soleus muscles were dissected and processed
      for light microscopy and submitted to morphological analysis. Results: The nerve
      compression promoted morphological changes, typical of denervation, and the
      treatment with vanillin was responsible for different responses in the studied
      muscles. For the tibialis anterior, there was an increase in the number of
      satellite cells, central nuclei and fiber atrophy, as well as fascicular
      disorganization. In the soleus, only increased vascularization was observed, with
      no exacerbation of the morphological alterations in the fibers. Conclusion: The
      treatment with vanillin promoted increase in intramuscular vascularization for
      the muscles studied, with pro-inflammatory potential for tibialis anterior, but
      not for soleus muscle. Objetivo: Avaliar a acao da vanilina (Vanilla planifolia)
      sobre a morfologia dos musculos tibial anterior e soleo apos lesao nervosa
      periferica. Metodos: Ratos Wistar foram divididos em quatro grupos, com sete
      animais cada, sendo Grupo Controle, Grupo Vanilina, Grupo Lesao e Grupo Lesao +
      Vanilina. Os animais dos Grupos Lesao e Grupo Lesao + Vanilina foram submetidos a
      lesao nervosa por meio da compressao do nervo isquiatico, e os Grupos Vanilina e
      Grupo Lesao + Vanilina foram tratados diariamente com doses orais de vanilina
      (150mg/kg) do 3o ao 21o dia apos a inducao da lesao nervosa. Ao termino do
      experimento, os musculos tibial anterior e soleo foram dissecados e seguiram o
      processamento de rotina em microscopia de luz, para posterior analise
      morfologica. Resultados: A compressao nervosa promoveu alteracoes morfologicas
      caracteristicas de denervacao, sendo que o tratamento com vanilina foi
      responsavel por respostas distintas nos musculos estudados. Para o tibial
      anterior, houve aumento do numero de celulas satelites, nucleos centrais e
      atrofia das fibras, bem como desorganizacao fascicular. Ja no soleo, houve apenas
      aumento da vascularizacao, sem exacerbacao das alteracoes morfologicas nas
      fibras. Conclusao: O tratamento com vanilina promoveu o aumento da vascularizacao
      intramuscular para os musculos estudados, com potencial pro-inflamatorio para o
      tibial anterior, o que nao ocorreu no musculo soleo.

PMID- 28767919
TI  - Assessment of operative times of multiple surgical specialties in a public
      university hospital.
AB  - Objective: To evaluate the indicators duration of anesthesia, operative time and
      time patients stay in the operating rooms of different surgical specialties at a
      public university hospital. Methods: It was done by a descriptive cross-sectional
      study based on the operating room database. The following stages were measured:
      duration of anesthesia, procedure time and patient length of stay in the room of
      the various specialties. We included surgeries carried out in sequence in the
      same room, between 7:00 a.m. and 5 p.m., either elective or emergency. We
      calculated the 80th percentile of the stages, where 80% of procedures were below
      this value. Results: The study measured 8,337 operations of 12 surgical
      specialties performed within one year. The overall mean duration of anesthesia of
      all specialties was 178.12+/-110.46 minutes, and the 80th percentile was 252
      minutes. The mean operative time was 130.45+/-97.23 minutes, and the 80th
      percentile was 195 minutes. The mean total time of the patient in the operating
      room was 197.30+/-113.71 minutes, and the 80th percentile was 285 minutes. Thus,
      the variation of the overall mean compared to the 80th percentile was 41% for
      anesthesia, 49% for surgeries and 44% for operating room time. In average,
      anesthesia took up 88% of the operating room period, and surgery, 61%.
      Conclusion: This study identified patterns in the duration of surgery stages. The
      mean values of the specialties can assist with operating room planning and reduce
      delays. Objetivo: Avaliar os indicadores de tempo da anestesia, da operacao e da
      permanencia do paciente em sala de diversas especialidades do centro cirurgico de
      um hospital universitario. Metodos: Foi realizado em estudo descritivo
      transversal a partir da base de dados do centro cirurgico e mensuradas as
      seguintes etapas: duracao de anestesia, tempo do procedimento e tempo de
      permanencia do paciente em sala das diversas especialidades. Foram incluidas as
      operacoes realizadas em sequencia na mesma sala, das 7h as 17h, eletivas ou de
      urgencias. Realizamos o calculo do percentil 80 da duracao das etapas, onde 80%
      dos procedimentos ficaram abaixo deste valor obtido. Resultados: O estudo incluiu
      8.337 operacoes realizadas no periodo de 1 ano de 12 especialidades cirurgicas. A
      media geral da duracao da anestesia de todas as especialidades foi de 178,12+/
      110,46 minutos, e o percentil 80 foi de 252 minutos. A media do tempo operatorio
      foi 130,45+/-97,23 minutos, e o percentil 80 foi de 195 minutos. A media do tempo
      total do paciente em sala operatoria foi de 197,30+/-113,71 minutos, e o
      percentil 80 foi de 285 minutos. A variacao da media geral em relacao ao
      percentil 80 foi de 41% na anestesia, 49% nas operacoes e 44% no tempo de sala.
      Na media geral, a anestesia ocupou 88% do tempo de sala e a operacao, 61%.
      Conclusao: Este estudo identificou padroes nas duracoes das etapas das operacoes.
      A informacao das medias historicas das especialidades pode auxiliar no
      planejamento do centro cirurgico e diminuir os atrasos.

PMID- 28767918
TI  - Economic analysis of costs with enteral and parenteral nutritional therapy
      according to disease and outcome.
AB  - Objective: To conduct an economic analysis of enteral and parenteral diet costs
      according to the type of disease and outcome (survivors versus deaths). Methods:
      It is a cross-sectional, observational, retrospective study with a qualitative
      and quantitative design, based on analysis of hospital accounts from a healthcare
      insurance provider in the Southern region of Brazil. Results: We analyzed 301
      hospital accounts of individuals who used enteral and parenteral diets. The total
      cost of the diet was 35.4% of hospital account total costs. The enteral modality
      accounted for 59.8% of total dietary costs. The major costs with diets were
      observed in hospitalizations related to infections, cancers and cerebro
      cardiovascular diseases. The major costs with parenteral diet were with
      admissions related by cancers (64.52%) and dementia syndromes (46.17%). The
      highest ratio between total diet costs with the total of hospital account costs
      was in dementia syndromes (46.32%) and in cancers (41.2%). The individuals who
      died spent 51.26% of total of hospital account costs, being 32.81% in diet
      (47.45% of total diet value and 58.81% in parenteral modality). Conclusion:
      Enteral and parenteral nutritional therapies account for a significant part of
      the costs with hospitalized individuals, especially in cases of cancers and
      dementia syndromes. The costs of parenteral diets were higher in the group of
      patients who died. Objetivo: Realizar uma analise economica de custos da terapia
      nutricional enteral e parenteral, conforme o tipo de doenca e o desfecho
      (sobreviventes versus obitos). Metodos: Estudo transversal, observacional,
      retrospectivo, com estrategia qualitativa e quantitativa, a partir da analise de
      contas hospitalares de uma operadora de saude da Regiao Sul do Brasil.
      Resultados: Foram analisadas 301 contas hospitalares de usuarios que utilizaram
      dieta enteral e parenteral. O custo total com dieta foi de 35,4% do custo total
      das contas hospitalares. A modalidade enteral representou 59,8% do custo total em
      dieta. Os maiores custos com dieta foram observados em internacoes relacionadas a
      infeccoes, canceres e doencas cerebro-cardiovasculares. Os maiores custos com
      dieta parenteral foram observados nas internacoes relacionadas aos canceres
      (64,52%) e as sindromes demenciais (46,17%). A maior relacao entre o custo total
      com dieta e o custo total da conta foi na sindrome demencial (46,32%) e no cancer
      (41,2%). Os usuarios que foram a obito consumiram 51,26% dos custos totais das
      contas, sendo 32,81% com dieta (47,45% do valor total com dieta e 58,81% do custo
      na modalidade parenteral). Conclusao: As terapias nutricionais enteral e
      parenteral representaram uma parte importante dos custos no tratamento de
      individuos hospitalizados, principalmente nos casos dos canceres e nas sindromes
      demenciais. O custo com dieta parenteral foi maior no grupo de usuarios que foram
      a obito.

PMID- 28767920
TI  - Implementing apportionment strategy to identify costs in a multidisciplinary
      clinic.
AB  - Objective: To present the implementation of an apportionment strategy
      proportional to the productive areas of a multidisciplinary clinic, defining the
      minimum values to be passed monthly to health professionals who work there.
      Methods: A study of the clinic structure was carried out, in which the area of
      occupation of each service was defined. Later the cost was prorated, allocating a
      value to each room, proportional to the space occupied. Results: The
      apportionment implementation allowed the clinic managers to visualize the cost of
      each room, providing a value base for formation of a minimum amount necessary to
      be passed monthly to each professional, as a form of payment for rent of using
      their facilities. Conclusion: The risk of financial loss of the clinic was
      minimized due to variation of its productivity, as well as the conditions of
      transference at the time of hiring by professionals were clear, promoting greater
      confidence and safety in contract relations. Objetivo: Apresentar a implantacao
      de uma estrategia de rateio proporcional as areas produtivas de uma clinica
      multidisciplinar, definindo valores minimos a serem repassados mensalmente aos
      profissionais de saude que as ocupam. Metodos: Estudo da estrutura da clinica, no
      qual foi definida, em metros quadrados, a area de ocupacao de cada servico. Em
      seguida, o custo foi rateado, alocando um valor a cada sala, proporcional ao
      espaco ocupado. Resultados: A implantacao do rateio possibilitou aos gestores da
      clinica estudada visualizar o custo de cada sala, fornecendo uma base de valor
      para formacao de um valor minimo necessario a ser repassado mensalmente para cada
      profissional, como forma de pagamento pelo aluguel de utilizacao de suas
      instalacoes. Conclusao: Minimizou-se o risco de prejuizo da clinica pela variacao
      de sua produtividade, bem como ficaram claras as condicoes de repasse no momento
      de contratacao do aluguel pelos profissionais, promovendo maior confianca e
      seguranca na relacao contratual.

PMID- 28767922
TI  - Pemphigus foliaceus as a differential diagnosis in vesicobullous lesions.
AB  - Given the challenge of clinical diagnosis of bullous skin lesions, this report
      aimed to discuss the histological changes, the presentation and clinical
      reasoning for diagnosis of these lesions. At the same time, the importance of the
      pathology was reviewed to identify these clinical scenarios. In this case report,
      we highlighted the clinical progression of a case of pemphigus foliaceus. RESUMO
      Considerando o desafio do diagnostico clinico de lesoes cutaneas de apresentacao
      bolhosa, o presente trabalho procurou discutir as alteracoes histologicas, a
      apresentacao e o raciocinio clinico para o diagnostico de tais lesoes.
      Paralelamente, a importancia da patologia foi revisada na identificacao destes
      quadros. Neste relato de caso, destaca-se a evolucao clinica de um quadro de
      penfigo foliaceo.

PMID- 28767921
TI  - Hospitalization costs of severe bacterial pneumonia in children: comparative
      analysis considering different costing methods.
AB  - Objective: To determine and compare hospitalization costs of bacterial community
      acquired pneumonia cases via different costing methods under the Brazilian Public
      Unified Health System perspective. Methods: Cost-of-illness study based on
      primary data collected from a sample of 59 children aged between 28 days and 35
      months and hospitalized due to bacterial pneumonia. Direct medical and non
      medical costs were considered and three costing methods employed: micro-costing
      based on medical record review, micro-costing based on therapeutic guidelines and
      gross-costing based on the Brazilian Public Unified Health System reimbursement
      rates. Costs estimates obtained via different methods were compared using the
      Friedman test. Results: Cost estimates of inpatient cases of severe pneumonia
      amounted to R$ 780,70/$Int. 858.7 (medical record review), R$ 641,90/$Int. 706.90
      (therapeutic guidelines) and R$ 594,80/$Int. 654.28 (Brazilian Public Unified
      Health System reimbursement rates). Costs estimated via micro-costing (medical
      record review or therapeutic guidelines) did not differ significantly (p=0.405),
      while estimates based on reimbursement rates were significantly lower compared to
      estimates based on therapeutic guidelines (p<0.001) or record review (p=0.006).
      Conclusion: Brazilian Public Unified Health System costs estimated via different
      costing methods differ significantly, with gross-costing yielding lower cost
      estimates. Given costs estimated by different micro-costing methods are similar
      and costing methods based on therapeutic guidelines are easier to apply and less
      expensive, this method may be a valuable alternative for estimation of
      hospitalization costs of bacterial community-acquired pneumonia in children.
      Objetivo: Determinar e comparar custos hospitalares no tratamento da pneumonia
      bacteriana adquirida na comunidade por diferentes metodologias de custeio, na
      perspectiva do Sistema Unico de Saude. Metodos: Estudo de custo, com coleta de
      dados primarios de uma amostra de 59 criancas com 28 dias a 35 meses de idade
      hospitalizadas por pneumonia bacteriana. Foram considerados custos diretos
      medicos e nao medicos. Tres metodologias de custeio foram utilizadas:
      microcusteio por revisao de prontuarios, microcusteio considerando diretriz
      terapeutica e macrocusteio por ressarcimento do Sistema Unico de Saude. Os custos
      estimados pelas diferentes metodologias foram comparados utilizando o teste de
      Friedman. Resultados: Os custos hospitalares de criancas com pneumonia grave
      foram R$ 780,70 ($Int. 858.7) por revisao de prontuarios, R$ 641,90 ($Int.
      706.90) por diretriz terapeutica e R$ 594,80 ($Int. 654.28) por ressarcimento do
      Sistema Unico de Saude, respectivamente. A utilizacao de metodologias de
      microcusteio (revisao de prontuarios e diretriz) resultou em estimativas de
      custos equivalentes (p=0,405), enquanto o custo estimado por ressarcimento foi
      significativamente menor do que aqueles estimados por diretriz (p<0,001) e por
      revisao de prontuario (p=0,006), sendo, assim, significativamente diferentes.
      Conclusao: Na perspectiva do Sistema Unico de Saude, existe diferenca
      significativa nos custos estimados quando se utilizam diferentes metodologias,
      sendo a estimativa por ressarcimento a que resulta em valores menores.
      Considerando que nao ha diferenca nos valores de custos estimados por diferentes
      metodologias de microcusteio, a metodologia de custeio por diretriz, de mais
      facil e rapida execucao, e uma alternativa valida para estimativa de custos de
      hospitalizacao por pneumonias bacterianas em criancas.

PMID- 28767923
TI  - Surgical correction of ectopic penis and scrotum associated with bilateral
      orchidopexy.
AB  - Ectopic penis is usually associated with penoscrotal transposition, and it is
      rarely observed in isolation. We report a surgical approach for an extremely rare
      case. A 10-year-old male patient with bilateral cryptorchidism and ectopic penis
      and scrotum in perineal area, with no penoscrotal transposition, representing an
      association not yet described in literature. A previous orchiopexy failed due to
      ectopic scrotum. By means of an inverted Y incision, the penis was mobilized and
      a perineal skin flap in form of a testicular sac was prepared. Finally orchiopexy
      was performed. The surgery was essential to treat cryptorchidism and to improve
      the self-image of the patient. RESUMO O penis ectopico geralmente ocorre
      associado a transposicao peno-escrotal, sendo raro isoladamente. Relatamos uma
      abordagem cirurgica para um caso extremamente raro. Tratava-se de paciente do
      sexo masculino, 10 anos, com criptorquidia bilateral e penis e escroto ectopicos,
      na regiao perineal, sem transposicao peno-escrotal, representando uma associacao
      ainda nao descrita na literatura. Orquidopexia previa sem sucesso, devido a
      ectopia do escroto. Por meio de uma incisao em Y invertido, mobilizou-se o penis
      e preparou-se um retalho da pele perineal em forma de bolsa testicular. Por fim,
      realizou-se a orquidopexia. A cirurgia foi fundamental para tratar a
      criptorquidia e promover ganho na autoimagem do paciente.

PMID- 28767924
TI  - Elderly with knee osteoarthritis should perform nutritional assessment:
      integrative literature review.
AB  - To review scientific literature to assess nutritional status of elderly patients
      with osteoarthritis in the last 16 years. This is an integrative literature
      review that included articles published in national and international journals
      indexed in PubMed, SciELO and BIREME. We selected 14 articles, and English
      language was predominant. The year of publication of articles ranged from 2006 to
      2016, and most of papers were cross-sectional studies. To gather papers and for
      posterior evaluate, we used a validated data collection instrument and the
      included studies were critical analyzed by reading, gathering and analysis of
      articles. Studies suggested that there is a positive correlation between obesity
      and knee osteoarthritis. Obesity is one of the most important modifiable factors
      in worsening of osteoarthritis symptoms. RESUMO O objetivo da pesquisa foi
      revisar a producao cientifica referente a avaliacao do estado nutricional de
      idosos com osteoartrite nos ultimos 16 anos. Assim, o estudo foi uma revisao
      integrativa da literatura, realizada com a busca de artigos publicados em
      periodicos nacionais e internacionais indexados no PubMed, na SciELO e na BIREME.
      Foram selecionados 14 artigos, e o idioma ingles foi preponderante. O periodo de
      publicacao dos artigos variou de 2006 a 2016, com predominancia de estudos do
      tipo transversais. Para reunir os artigos e para posterior avaliacao, foi
      utilizado um instrumento de coleta de dados validado, e as analises criticas dos
      estudos incluidos foram realizadas por meio da leitura, do agrupamento e da
      analise dos artigos. As pesquisas sugeriram que existe correlacao positiva entre
      obesidade e osteoartrite de joelhos. Alem disto, a obesidade e um dos fatores
      mais significativos e modificaveis no agravamento dos sintomas da osteoartrite.

PMID- 28767925
TI  - Autism spectrum disorders: an updated guide for genetic counseling.
AB  - Autism spectrum disorder is a complex and genetically heterogeneous disorder,
      which has hampered the identification of the etiological factors in each patient
      and, consequently, the genetic counseling for families at risk. However, in the
      last decades, the remarkable advances in the knowledge of genetic aspects of
      autism based on genetic and molecular research, as well as the development of new
      molecular diagnostic tools, have substantially changed this scenario. Nowadays,
      it is estimated that using the currently available molecular tests, a potential
      underlying genetic cause can be identified in nearly 25% of cases. Combined with
      clinical assessment, prenatal history evaluation and investigation of other
      physiological aspects, an etiological explanation for the disease can be found
      for approximately 30 to 40% of patients. Therefore, in view of the current
      knowledge about the genetic architecture of autism spectrum disorder, which has
      contributed for a more precise genetic counseling, and of the potential benefits
      that an etiological investigation can bring to patients and families, molecular
      genetic investigation has become increasingly important. Here, we discuss the
      current view of the genetic architecture of autism spectrum disorder, and list
      the main associated genetic alterations, the available molecular tests and the
      key aspects for the genetic counseling of these families. RESUMO O transtorno do
      espectro autista e um disturbio complexo e geneticamente heterogeneo, o que
      sempre dificultou a identificacao de sua etiologia em cada paciente em particular
      e, por consequencia, o aconselhamento genetico das familias. Porem, nas ultimas
      decadas, o acumulo crescente de conhecimento oriundo das pesquisas sobre os
      aspectos geneticos e moleculares desta doenca, assim como o desenvolvimento de
      novas ferramentas de diagnostico molecular, tem mudado este cenario de forma
      substancial. Atualmente, estima-se que, por meio de testes moleculares, e
      possivel detectar uma alteracao genetica potencialmente causal em cerca de 25%
      dos casos. Considerando-se tambem a avaliacao clinica, a historia pre-natal e a
      investigacao de outros aspectos fisiologicos, pode-se atribuir uma etiologia para
      aproximadamente 30 a 40% dos pacientes. Assim, em vista do conhecimento atual
      sobre a arquitetura genetica do transtorno do espectro autista, que tem tornado o
      aconselhamento genetico cada vez mais preciso, e dos potenciais beneficios que a
      investigacao etiologica pode trazer aos pacientes e familiares, tornam-se cada
      vez mais importantes os testes geneticos moleculares. Apresentamos aqui uma breve
      discussao sobre a visao atual da arquitetura genetica dos transtornos do espectro
      autista, listando as principais alteracoes geneticas associadas, os testes
      moleculares disponiveis e os principais aspectos a se considerar para o
      aconselhamento genetico destas familias.

PMID- 28767926
TI  - The importance of apnea in patients undergoing angiography of thoracic vessels -
      a protocol for acute pulmonary thromboembolism research.

PMID- 28767927
TI  - Mindfulness in mood and anxiety disorders: a review of the literature.
AB  - INTRODUCTION: The objective of this study was to conduct a review of the
      literature covering the use of different mindfulness-based therapy approaches in
      treatment of mood and anxiety disorders, including mindfulness skills and
      mindfulness linked to emotional regulation and fear of negative appraisal.
      METHODS: A review was conducted of literature identified by searching the
      scientific databases PubMed and PsycINFO with the following keywords:
      mindfulness, mood disorders, and anxiety disorders. The search covered the past
      10 years. The search returned 532 articles, 24 were selected, their full texts
      were read, and 16 were included in this review. RESULTS: Six articles about
      mindfulness-based stress reduction, four about mindfulness-based cognitive
      therapy, and three about fear of negative appraisal and emotional regulation were
      reviewed. All of the articles covered mindfulness in relation to mood and anxiety
      disorders. CONCLUSIONS: The literature in this field suggests that mindfulness is
      an effective strategy for the treatment of mood and anxiety disorders and is
      effective in therapy protocols with different structures including virtual
      modalities. Use of mindfulness in scientific models continues to expand.

PMID- 28767929
TI  - ?

PMID- 28767928
TI  - Trends in the prescription of clozapine in a psychiatric hospital: a 5-year
      observational study.
AB  - INTRODUCTION: Clozapine is a well-recognized effective treatment for some
      patients with treatment-resistant schizophrenia (TRS). Although it has potential
      benefits and approximately 30% of patients have a clinical indication for
      clozapine use, prescription rates are low. OBJECTIVE: To evaluate clozapine
      prescription trends over a 5-year period in a tertiary psychiatric hospital.
      METHODS: In this observational study, data prospectively collected by the Medical
      and Statistical File Service (Servico de Arquivo Medico e Estatistico) and the
      Pharmacy Division of Instituto de Psiquiatria de Santa Catarina between January
      2010 and December 2014 were summarized and analyzed by investigators blinded to
      data collection. The number of 100 mg clozapine pills dispensed by the Pharmacy
      Division to the inpatient units was the outcome and considered a proxy measure of
      clozapine prescriptions. The number of occupied inpatient unit beds and the
      number of patients admitted with F20-F29 (ICD-10) diagnoses during the study
      period were considered to be possible confounders. RESULTS: A multiple linear
      regression model showed that time in months was independently associated with an
      increase in the number of clozapine pills dispensed by the Pharmacy Division
      (beta coefficient = 15.82; 95% confidence interval 10.88-20.75). CONCLUSION:
      Clozapine prescriptions were found to have increased during the 5-year period
      studied, a trend that is opposite to reports from several other countries.

PMID- 28767930
TI  - [Patterns of maternal-child nursing home-visit].
AB  - Here is presented patterns for the maternal-child nursing home-visit, nursing
      auxiliary personnel. The objective of tris article is to orient nursing auxiliary
      personeal responsible for maternal-newborn child home visiting. It contains
      detailed information on what to do when normal as well as abnormal conditions are
      found.

PMID- 28767931
TI  - [Nurse-patient relationship: theoric considerations and account of an experience
      in teaching].
AB  - The authors discuss the teaching of therapeutic relationship to undergraduated
      nursing students, including its praticai application. They exemplify it with the
      account of a case of student-patient relationship.

PMID- 28767932
TI  - [Legal aspects of the Code of Deontology for nursing personnel].
AB  - The author compares the rules contained in the Code of Deontology, of the Nursing
      Federal Council, and in the Code of Ethics, of the Brazilian Nurses' Association,
      with the equivalent precepts of the Civil Code and Penal Code of Brazil.

PMID- 28767933
TI  - [Standards to be observed in basic nursing procedures].
AB  - The authors present as an aid to teaching, a guide of some basic nursing
      procedures, described according to the norms to be observed.

PMID- 28767934
TI  - [Growth rate and sexual development in rats with protein valorie malnutrition].
AB  - The authors studied the effect of two dietetics treatments, that allow the
      animals to have the same growth rate, upon the time of onset of puberty.

PMID- 28767935
TI  - [Nursing care of patients with antisocial behavior as manifestation of
      personality disorder].
AB  - The authors discuss how nursing personnel should deal with patients who suffer
      from personality disorders when they show signs of antisocial behavior.

PMID- 28767936
TI  - [Influence of nursing care in the prevention of hyperemesis gravidarum].
AB  - The objectives of this study was to find out if nursing assistance given to
      pregnant women, specifically in relation to nauses and vomiting, would help
      prevent hyperemesis gravidarum. Nursing assistance consisted basically in
      orientation regarding diet and help in the solution of emotional problems, both
      given to the palienles when they came to the out patient department for pre-natal
      control. Thirty pregnant women were studied. The data obtained were not
      significant, due probabity to a number of causes, including: small population;
      infrequent nurse-patient meetings; lack of control over the patients' diet. This
      study was therefore considered as a pilot study.

PMID- 28767937
TI  - [Bibliografy review about prophylaxis of gonococcal ophthalmia in the newborn].
AB  - In 1881, Crede introduced the ocular instillation of silver-nitrate solution in
      the newborn, after the birth, for the prophylaxis of gonococcal ophthalmia
      neonatorum. Although the Crede Method has been used for almost one hundred years,
      there is controversy among authors about the indications, the way of application
      and the replacement of anti-bacterial agent. The studies about gonococcal
      ophthalmia neonatorum and gonorrhea in pregnant women were all made in hospitals;
      no national statistics are available. The problems of failure and risk of Crede
      Method is attributed to the improper application of silver-nitrate solution. The
      author suggests continuation of tlie routine of Crede Method in all newborns.

PMID- 28767938
TI  - [Nursing assistence to hospitalized children in straightened circunstances (part
      II)].
AB  - In this part, the second of a series of reports, two experiences are referred
      concerning the help given by two students in Pediatrics Nursing to hospitalized
      children, in order to help them to cope with a surgery situation and to obtain
      their cooperation.

PMID- 28767939
TI  - [A comparative study of the sexual knowledge of 15 to 17 year age high school
      students of Greater Sao Paulo: previous note].

PMID- 28767940
TI  - ?

PMID- 28767941
TI  - [A brest-feeding study].
AB  - As an introduction the authors consider the advantages of breast-feeding,
      describing the social-economic causes which are influencing, the abandonment of
      this practice in the world. Following this they describe and comment on the
      results of a research project carried out with a group of mothers, which had as
      its objective to study some aspects relative to breast-feeding children.

PMID- 28767942
TI  - ["Residency" in nursing: advantages and disadvantages].
AB  - A study about "residency" in nursing is started. The purposes, goals, advantages
      and disadvantages related to this subject are considered. A fact-facing mind of
      today's nursing is necessary.

PMID- 28767943
TI  - [The sistemic theory applied to health].
AB  - The author consideres the Sistems Theory and its application to health, with a
      brief analysis of some aspects of this theory wich were presented at the 5th
      National Health Conference in 1975.

PMID- 28767944
TI  - [A study of the child's arterial pressure: announcement].

PMID- 28767945
TI  - ?

PMID- 28767946
TI  - ?

PMID- 28767947
TI  - [Cardiovasculares parameters' observation in infarted patients face relative's
      visit].
AB  - This survey was made with 20 infarcted patients; and their blood pressure and
      cardiac rate were examined before and after the visit of relative. It was
      verified that they showed alterations due to emotional situations.

PMID- 28767948
TI  - [Intolerance glucose control in the parenteral hyperalimentation].
AB  - Ten non-diabetic surgical patients, submitted to parenteral hyperalimentation,
      were prospectively studied, in order to determine the incidence of glucose
      intolerance during this treatment. Additionally three methods for the control of
      glucose metabolism, namely glucosuria and gtycemia, given by reagent strips, and
      standard blood sugar, determined at the auto-analyser, were compared, with the
      purpose of establishing which of these tests is best suited for routine
      utilization. It was concluded that: 1) The incidence of glucose intolerance,
      defined as one or more episodes of positive glucosuria, or of blood sugar higher
      than 180mg/100 ml, was 60% in the first day of intravenous nutrition, and 80% if
      the whole period of treatment; 2) Glucose intolerance was more often detected by
      urine testing than by blood determinations, either with Dextrositx or at the a
      auto-analyser as the glucosuria test: was performed much more frequently; 3) It
      is concluded that although the findings of tests for glucosuria may not
      adequately reflect glucose metabolism in all circumstances, they represent the
      choice examination for basic monitoring of patients receiving intravenous
      hyperalimentation, as soon as renal function is satisfactory, because of its low
      expense and its easy application.

PMID- 28767949
TI  - [A model of nursing consultation in child health].
AB  - This work presents a model of nursing consultation for use in the assistance of
      infants (up to one year). It is being used in field teaching of Public Health
      Nursing, at the School of Nursing, University of Sao Paulo, Brasil.

PMID- 28767950
TI  - [Urine exam: all strictness in collecting samples].
AB  - Urine Type I laboratorial exam anl it's physical, chemical and microscopic
      characteristics are presented, as novell as the care needed for it's collection,
      order to oftain accurate results in the analysis of urianry elements.

PMID- 28767951
TI  - [The protection of the perineoum of the patient during the delivery of the head
      and shoulders of the fetus].
AB  - The authors describe a technique of perineoum protection during the delivery of
      the fetus head and shoulders.

PMID- 28767952
TI  - [The assistance function performed by the nurse in State Health Centers of Sao
      Paulo].
AB  - The author relates the results of a study made in the State Health Centers, Sao
      Paulo, Brazil. Her aim was to analyse the activities of the nurses wren
      performing nursing assistance functions to the users of the health units.

PMID- 28767953
TI  - [Surgical positions and their implications in nursing care].
AB  - This article brings into focus the importance of the patients position during
      surgery and its implication for nursng care.

PMID- 28767954
TI  - [Present aspects of neuropsychosurgery nursing].
AB  - A brief review of the medical literature, on neuropsychosurgery and the specific
      aspects of nursing care are presented. Emphasis is given to the importance of an
      objective attitude towards the results of this type of surgery.

PMID- 28767955
TI  - [Libraries of Schools and Schools for Practical Nurses in Sao Paulo, Brasil].
AB  - This is a survey made in thirty nine Schools for Practical Nurses in Sao Paulo,
      Brasil, 1978, about library resources. The aspects surveyed were number and type
      of books and journals, physical area used as library and its organization.

PMID- 28767956
TI  - [Instrument of communication between the surgical ward and the operating room:
      previous note].

PMID- 28767957
TI  - Obesity and public policies: the Brazilian government's definitions and
      strategies.
AB  - The study analyzes national strategies for dealing with obesity in Brazil in the
      framework of the Brazilian Unified National Health System (SUS) and the Food and
      Nutritional Security System (SISAN). Based on the document analysis method, we
      examined government documents produced in the last 15 years in the following
      dimensions: definitions of obesity, proposed actions, and strategies for linkage
      between sectors. In the SUS, obesity is approached as both a risk factor and a
      disease, with individual and social/environmental approaches aimed at changing
      eating practices and physical activity. In the SISAN, obesity is also conceived
      as a social problem involving food insecurity, and new modes of producing,
      marketing, and consuming foods are proposed to change eating practices in an
      integrated way. Proposals in the SUS point to an integrated and intra-sector
      approach to obesity, while those in SISAN emphasize the problem's inter-sector
      nature from an expanded perspective that challenges the prevailing sector-based
      institutional structures.

PMID- 28767958
TI  - Strategic factors for the sustainability of a health intervention at municipal
      level of Brazil.
AB  - The present study aims to describe the evolution of an intervention, using a
      methodology that adopts the critical event as the unit of analysis, and to
      identify strategic factors that facilitate the continuation of the interventions.
      Six critical events were identified: dispute care models for health; area of
      advice: dispute field; change policy; break of interorganizational relations;
      lack of physical structure and turnover of staff; difficulty in organizing
      practices in the work process. these are developed into strategic factors:
      enabling network of allies; meetings and educational activities/building
      capacity; benefits perceived by community members; mobilization of key actors;
      intervention's compatibility with the government's vision; restoration of
      interrelationship; and stability of the workforce. These strategic factors form a
      group of interrelated conditions that provide the strengthened linkages between
      elements in the intervention, supporting the hypothesis that they collaborate for
      the sustainability of the interventions in health. Tracking down the
      transformations of an intervention set by the critical events, it was verified
      that these factors performed a protective role at times of changes in the
      intervention process.

PMID- 28767959
TI  - Occupational exposure to hydrogen cyanide during large-scale cassava processing,
      in Alagoas State, Brazil.
AB  - The cassava roots used for flour production contain high amounts of cyanogenic
      glycosides and are, therefore, potential hydrogen cyanide (HCN) releasers. This
      fact is the cause of an increasing health concern in the sector of cassava
      processing. Brazilian workers engaged in the flour production may be chronically
      exposed to HCN in levels above the safety limits. This hypothesis is based on the
      drastic reduction in cyanide content of cassava roots during a traditional
      Brazilian method of processing and in the physical properties of the compound,
      which makes it very susceptible to volatilization and air contamination. As an
      attempt to explore this issue, HCN exposure in Brazilian "flour houses" was
      evaluated in this study through environmental and biological monitoring. Four
      flour houses placed in Alagoas State, Brazil, were investigated. The results
      indicated that the cassava processors are chronically exposed to HCN at average
      levels between 0.464 and 3.328mg/m3 (TWA), in the work environment. This range is
      below the TLV-C of 5mg/m3 but not below the Action Level of 2.5mg/m3. These data
      may be interpreted as a possible risk to susceptible individuals. Additionally,
      the biological monitoring indicated a high cyanide exposure in the population
      study, considering urinary thiocyanate (SCN-) levels.

PMID- 28767960
TI  - Obesity prevention and control: the urgent need for effective public policies.

PMID- 28767961
TI  - [Use of industrial liquid silicone to transform the body: prevalence and factors
      associated with its use among transvestites and transsexual women in Sao Paulo,
      Brazil].
AB  - This study aimed to estimate the prevalence of use of industrial liquid silicone
      (ILS) among transvestite persons and transsexual women and identify associated
      factors. This was a cross-sectional study in seven municipalities in Sao Paulo
      State, Brazil, with data collected in 2014 and 2015 in a sample of 576
      individuals. Analysis of the associated factors used a Poisson model with robust
      variance to estimate the crude and adjusted prevalence ratios. Prevalence of use
      of ILS was 49%, mean age at first injection of ILS was 22 (+/- 5.3) years, and
      43% reported health problems resulting from its use. Having less than a
      university education, age 20 years and older, self-identification as
      transvestite, and sex work were positively associated with use of ILS according
      to the multivariate model. There was a high prevalence of ILS use and resulting
      health problems, indicating the need to prevent its use and reduce the resulting
      health problems. It is thus essential to ensure access to the necessary resources
      for body changes during transition through comprehensive care for transvestites
      and transsexual persons in the Brazilian Unified National Health System (SUS).
      Finally, health policies should include demands for body changes as part of
      gender identity construction, respecting each person's unique needs in this
      transition process.

PMID- 28767962
TI  - Cyber dating abuse in affective and sexual relationships: a literature review.
AB  - Cyber culture with its related e-commerce, expanded since the 2000s through the
      advent of social network platforms, incites participants to engage in hyper
      exposure and spectacularization of their private lives, with inherent
      consequences for personal image and privacy, publicizing private matters
      (especially those pertaining to sexuality and corporality) in the digital media.
      This raises the need to understand how the phenomenon of cyber dating abuse in
      affective and sexual relationships is conceptualized and characterized in
      scientific studies, which health problems are associated with it, and which
      social technologies are suggested for intervention. This form of abuse is a new
      expression of intimate partner violence that involves, among other practices,
      posting embarrassing photos and videos and intimate messages without prior
      consent, with the purpose of humiliating and defaming the person. The current
      study is an integrative systematic review, including 35 articles, with a
      predominance of studies in the United States (22). Types of cyber dating abuse
      range from direct aggression to stalking. Despite the high prevalence, especially
      among adolescents and youth, the literature highlights that this type of cyber
      abuse is often taken for granted. The suggested interventions are mostly for
      prevention and awareness-raising concerning relationship abuse, action by school
      counselors, and family orientation. The high reciprocity of cyber dating abuse
      between males and females indicates that future studies should attempt to
      elucidate how the dynamics of gender violence are reproduced or subverted by it.

PMID- 28767963
TI  - [The flexibilization of the Brazilian legislation on pesticides and the risks to
      human health: analysis of Bill of Law 3,200/2015].
AB  - This article aims to contribute to a reflection on pesticides, based on the
      Brazilian legal framework, from the perspective of protecting human health and
      the environment. This initiative is due to successive attempts to flexibilize the
      regulation of pesticides in Brazil, through bills of law in progress in the
      Brazilian National Congress. An analysis of Bill of Law 3,200/2015 was carried
      out. This bill of law represents a major setback to the legislative achievements
      for the regulation of pesticides, in order to alert to the risks to human health
      from exposure to these products and aggravated by other similar proposals.

PMID- 28767964
TI  - [International migration, health, and work: an analysis of Haitians in Mato
      Grosso State, Brazil].
AB  - This article addresses the relations between immigration, health, and work in
      Haitian immigrants in Cuiaba and Varzea Grande, Mato Grosso State, Brazil,
      emphasizing their work conditions. This was an exploratory study based on primary
      data collected through a survey of the Haitian population in Cuiaba in 2014-2015.
      A total of 452 Haitians were interviewed, living in Cuiaba and Varzea Grande (373
      men and 79 women), and the findings point to the precarious social situation of
      Haitian immigrants in Mato Grosso State, marked by high unemployment. Of the
      immigrants interviewed, 52.7% were currently working and 26.5% reported a
      workweek greater than 48 hours. The two main occupations for Haitian immigrants
      in Cuiaba were construction and services, and most were working below their
      original level of training, skills sets, and job experience in Haiti. The main
      risks identified in these two sectors were physical (53.2% and 63.4%,
      respectively) and accidents (23.4% and 17.1%, respectively), in addition to
      reports of physical and psychosocial distress. The study points to the precarious
      social, economic, and labor conditions of the Haitian population in the capital
      of Mato Grosso.

PMID- 28767966
TI  - ?

PMID- 28767965
TI  - Plain packaging of tobacco products in Brazil: the contribution of science to the
      decision to safeguard the human right to health.

PMID- 28767967
TI  - [An Approach to nutritional care].
AB  - This work includes an approach to nutritional care and it's activities in nursing
      assistance.

PMID- 28767968
TI  - [Teaching and professional adjustment].
AB  - Survey made among 23 graduated nurses that received their degree in EEUSP in
      1973. This survey tried to know if developed program was being suficient to
      prepare, professional people, to act as agents able to mantain the patterns of
      the nursing profession and able to increase continuosly the standards of
      professional practice.

PMID- 28767969
TI  - [Electrolyte imbalance in suckling with broncho - pneumonia].
AB  - The authors describe responsable mechanisms leading to electrolyte imbalance of
      the suckling with broncho - pneumonia. They outline the physiopathological and
      etiological nursing problems and present, as far as they believe, an adequate
      nursing treatment, focalyzing specific areas, such as: vital signs, skin and
      mucosa, nutrition and hidra-tion, voiding, sleep and rest, including sensory and
      phycho-social conditions.

PMID- 28767970
TI  - [Multiphasic and automatic health screening: offline and on-line methods].
AB  - The health screening methods have been suffering considerable modifications
      through the years. The introduction of the digital electronic computer and the
      clinical laboratory automation allowed us to reach a process known as
      "Multiphasic and Automatic Health Screening". "Multiphasic" because of the fact
      that various tests can be done (spirometry, E. C. G., audiometry, laboratory
      tests, etc.) and "Automatic" because of the utilization of the computer, the Auto
      Analyzer and other similar equipments. The results of the various tests can be
      evaluated by the computer in two ways: "on-line", when various equipments are
      directly connected to the processing unit, "off-line" when the results are
      preliminarily registered in a punch card, mark sense page etc. The two tecniques
      are described and exemplified with the University of Sao Paulo experience (off
      line method), and that of a private organization (on-line method), and the
      importance of that methodology in Preventive Medicine is emphasized.

PMID- 28767971
TI  - [Teaching medical-surgical nursing in especialization course - University of Sao
      Paulo's Nursing School - General aspects of medical-surgical nursing II
      discipline].
AB  - The authors present general aspects about planning a program in Medical-Surgical
      Nursing II in Especialization Course, since it's start in 1973 at University of
      Sao Paulo's Nursing School. It is presented the actual program including an
      esquematic plan regarding the teaching of the subject.

PMID- 28767972
TI  - [Why know research methodology].
AB  - Here is presented the increasing need of nurses to learm the research
      methodology, and discused the utilization, making and management of research,
      related to the development of nursing as a science.

PMID- 28767973
TI  - [Hospital infections: retrospective and present point of view].
AB  - The author presents a revision of the main facts linked to the infection problem.
      It reports several approaches of the subject and the present controversy.

PMID- 28767974
TI  - [Plan for teaching psychiatric nursing care when the patient is submited to
      psychiatric treatments].
AB  - This paper is a plan for teaching psychiatric nursing care when the patient is
      submited to psychiatric treatments. There is a full development of subjectives
      (cognitive, affective and psycho-motor domain), contents, strategies, auxiliar
      aids, students' activity, bibliografy and evaluation. This evaluation comprehends
      all objectives.

PMID- 28767975
TI  - Culex quinquefasciatus from areas with the highest incidence of microcephaly
      associated with Zika virus infections in the Northeast Region of Brazil are
      refractory to the virus.
AB  - Zika virus (ZIKV) is widely distributed in Brazil and the Northeast Region (NE)
      is the most affected zone, showing the highest incidence of microcephaly
      associated with ZIKV congenital infections worldwide. We report attempts to
      infect three populations of Culex quinquefasciatus from severely affected sites
      in the NE and Southeast Region (SE) of Brazil with three strains of ZIKV isolated
      from these localities. An Aedes aegypti population from the SE was used as a
      positive control. All tested Cx. quinquefasciatus populations were refractory to
      the ZIKV isolates. For these reasons, we believe Cx. quinquefasciatus should not
      be considered a potential vector of ZIKV in Brazil.

PMID- 28767976
TI  - Chikungunya virus: clinical aspects and treatment - A Review.
AB  - Chikungunya is a severe and debilitating disease. Currently, Brazil is
      experiencing an epidemic caused by three arboviruses, which has changed the way
      health professionals have diagnosed and treated infected patients. The difficulty
      of diagnosis and the lack of a protocol for patient treatment, which fits
      Brazilian health system models, have made it difficult to manage this disease. It
      is necessary to implement a multidisciplinary network of patient care, in which
      primary care units play the main role. This review aims to present current
      information regarding the clinical aspects and treatment of Chikungunya virus
      infection.

PMID- 28767977
TI  - Clinical and serological tests for arboviruses in free-living domestic pigeons
      (Columba livia).
AB  - BACKGROUND: In this study, we evaluated the role of free-living domestic pigeons
      (Columba livia) as a reservoir of arboviruses in the city of Belem, state of
      Para, Brazil. We investigated the presence of antibodies against the most
      prevalent arboviruses. OBJECTIVES: This study was aimed at evaluating some
      clinical and physical parameters of domestic pigeons, including the presence of
      antibodies to Amazon-endemic arboviruses. METHODS: Eighty-five healthy pigeons
      were captured in Mangal das Garcas Park, in Belem, and were bled. Upon capture,
      the birds were subjected to a clinical examination in search of alterations that
      could indicate the presence of arboviruses. Blood samples were converted to serum
      and tested using the haemagglutination inhibition (HI) technique with a panel of
      19 antigens of arboviruses circulating in the Amazon. The confirmation assay for
      the positive reactions to the viral species tested by HI was a neutralisation
      test in new-born Swiss albino mice (Mus musculus) [mouse neutralisation test
      (MNT)]. FINDINGS: A total of 10 (11.8%) serum samples tested positive for
      antiflavivirus antibodies by HI. All the samples positive for the HI test were
      subjected to MNT for detection of viruses and yielded negative results
      (logarithmic neutralisation index < 1.7). MAIN CONCLUSION: The results represent
      the first serological detection of antiarbovirus antibodies in domestic pigeons
      as potential hosts of arboviruses in Brazil. The detection of haemagglutination
      inhibiting antibodies against genus Flavivirus indicated that there was recent
      contact between the analysed domestic pigeons and these arboviruses. Further
      studies are needed to evaluate the role of free-living pigeons in the maintenance
      cycle and spread of arboviruses in the Amazon.

PMID- 28767978
TI  - Biosynthesized silver nanoparticles: are they effective antimicrobials?
AB  - BACKGROUND: Silver nanoparticles (AgNPs) are increasingly being used in medical
      applications. Therefore, cost effective and green methods for generating AgNPs
      are required. OBJECTIVES: This study aimed towards the biosynthesis,
      characterisation, and determination of antimicrobial activity of AgNPs produced
      using Pseudomonas aeruginosa ATCC 27853. METHODS: Culture conditions (AgNO3
      concentration, pH, and incubation temperature and time) were optimized to achieve
      maximum AgNP production. The characterisation of AgNPs and their stability were
      evaluated by UV-visible spectrophotometry and scanning electron microscopy.
      FINDINGS: The characteristic UV-visible absorbance peak was observed in the 420
      430 nm range. Most of the particles were spherical in shape within a size range
      of 33-300 nm. The biosynthesized AgNPs exhibited higher stability than that
      exhibited by chemically synthesized AgNPs in the presence of electrolytes. The
      biosynthesized AgNPs exhibited antimicrobial activity against Escherichia coli,
      P. aeruginosa, Salmonella typhimurium, Staphylococcus aureus, methicillin
      resistant S. aureus, Acinetobacter baumannii, and Candida albicans. MAIN
      CONCLUSION: As compared to the tested Gram-negative bacteria, Gram-positive
      bacteria required higher contact time to achieve 100% reduction of colony forming
      units when treated with biosynthesized AgNPs produced using P. aeruginosa.

PMID- 28767979
TI  - Risk factors for hepatitis B transmission in South Brazil.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem in
      Brazil. Several risk factors are involved in HBV infection and their
      identification by a rational and essential approach is required to prevent the
      transmission of this infection in Brazil. OBJECTIVES: To evaluate risk factors
      associated with HBV infection in South Brazil. METHODS: A total of 260 patients
      with HBV and 260 controls from Caxias do Sul (state of Rio Grande do Sul, Brazil)
      participated in this study. All participants were given a standard questionnaire
      to yield the sociodemographic information and to identify HBV risk factors. HBV
      infection was detected by HBsAg test in all participants. FINDINGS: HBV infection
      in these cases was strongly associated with history of a family member HBV
      infected, mainly mother [odds ratio (OR) = 4.86; 95% confidence intervals (CI):
      1.69-13.91], father (OR = 5.28; 95% CI: 1.58-17.71), and/or siblings (OR = 22.16;
      95% CI: 9.39-52.25); sharing personal objects (OR = 1.40; 95% CI: 1.37-2.38); and
      having history of blood transfusion (OR = 2.05; 95% CI: 1.10-2.84). CONCLUSIONS:
      HBV infection was strongly associated with having a family member infected with
      hepatitis B, sharing personal objects, and having history of blood transfusion.

PMID- 28767980
TI  - Bone marrow cell migration to the heart in a chimeric mouse model of acute
      chagasic disease.
AB  - BACKGROUND: Chagas disease is a public health problem caused by infection with
      the protozoan Trypanosoma cruzi. There is currently no effective therapy for
      Chagas disease. Although there is some evidence for the beneficial effect of bone
      marrow-derived cells in chagasic disease, the mechanisms underlying their effects
      in the heart are unknown. Reports have suggested that bone marrow cells are
      recruited to the chagasic heart; however, studies using chimeric mouse models of
      chagasic cardiomyopathy are rare. OBJECTIVES: The aim of this study was to
      investigate the migration of bone marrow cells to the heart after T. cruzi
      infection in a model of chagasic disease in chimeric mice. METHODS: To obtain
      chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation
      (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green
      fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft
      effectiveness was confirmed by flow cytometry. Experimental mice were divided
      into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT)
      mice, both of which received 3 * 104 trypomastigotes of the Brazil strain; (iii)
      non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. FINDINGS: At
      one-month post-infection, iChim and iWT mice showed first degree atrioventricular
      block with decreased heart rate and treadmill exercise parameters compared to
      those in the non-infected groups. MAIN CONCLUSIONS: iChim mice showed an increase
      in parasitaemia, myocarditis, and the presence of amastigote nests in the heart
      tissue compared to iWT mice. Flow cytometry analysis did not detect
      haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+
      cardiomyocytes were not detected in the tissues of chimeric mice.

PMID- 28767981
TI  - Protection mediated by chemokine CXCL10 in BALB/c mice infected by Leishmania
      infantum.
AB  - BACKGROUND: Visceral leishmaniasis (VL) caused by Leishmania infantum is
      characterised by the loss of the ability of the host to generate an effective
      immune response. Chemokines have a direct involvement in the pathogenesis of
      leishmaniasis, causing a rapid change in the expression of these molecules during
      infection by Leishmania. OBJECTIVES: Herein, it was investigated the role of
      CXCL10 in controlling infection by L. infantum. METHODS: RAW 264.7 macrophages
      were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50
      and 100 ng/mL). Parasite load, as well as nitric oxide (NO), IL-4 and IL-10
      production were assessed at 24 and 48 h after infection. In vivo, BALB/c mice
      were infected and treated or not with CXCL10 (5 MUg/kg) at one, three and seven
      days of infection. Parasite load, IFN-g, IL-4, TGF-beta and IL-10 were evaluated
      one, seven and 23 days post treatment. FINDINGS: In vitro, CXCL10 reduced
      parasitic load, not dependent on NO, and inhibited IL-10 and IL-4 secretion. In
      vivo, CXCL10 was able to reduce the parasite load in both liver and spleen, four
      weeks after infection, representing a higher decrease in the number of parasites
      in these organs, also induced IFN-gamma at day 23 after treatment, correlating
      with the decrease in parasite load, and reduced IL-10 and TGF-beta. MAIN
      CONCLUSIONS: This study suggests a partial protective role of CXCL10 against L.
      infantum, mediated by IFN-g, not dependent on NO, and with suppression of IL-10
      and TGF-beta. These data may provide information for the development of new
      approaches for future therapeutic interventions for VL.

PMID- 28767982
TI  - Description of an oral Chagas disease outbreak in Venezuela, including a
      vertically transmitted case.
AB  - We describe the eleventh major outbreak of foodborne Trypanosoma cruzi
      transmission in urban Venezuela, including evidence for vertical transmission
      from the index case to her fetus. After confirming fetal death at 24 weeks of
      gestation, pregnancy interruption was performed. On direct examination of the
      amniotic fluid, trypomastigotes were detected. T. cruzi specific-polymerase chain
      reaction (PCR) also proved positive when examining autopsied fetal organs.
      Finally, microscopic fetal heart examination revealed amastigote nests. Acute
      orally transmitted Chagas disease can be life threatening or even fatal for
      pregnant women and unborn fetuses owing to vertical transmission. There is
      therefore an urgent need to improve national epidemiologic control measures.

PMID- 28767983
TI  - Evidence for regulated expression of Telomeric Repeat-containing RNAs (TERRA) in
      parasitic trypanosomatids.
AB  - The Telomeric Repeat-containing RNAs (TERRA) participate in the homeostasis of
      telomeres in higher eukaryotes. Here, we investigated the expression of TERRA in
      Leishmania spp. and Trypanosoma brucei and found evidences for its expression as
      a specific RNA class. The trypanosomatid TERRA are heterogeneous in size and
      partially polyadenylated. The levels of TERRA transcripts appear to be modulated
      through the life cycle in both trypanosomatids investigated, suggesting that
      TERRA play a stage-specific role in the life cycle of these early-branching
      eukaryotes.

PMID- 28767984
TI  - Complete coding sequence of dengue virus serotype 4 isolated from field-caught
      mosquitoes in Thailand.
AB  - This report is the first to characterise the complete coding sequence of a dengue
      virus serotype 4 (DENV-4) genotype I that was isolated from field-caught
      mosquitoes from an endemic area in Thailand in June 2013. The sequence was
      assembled from high-throughput sequencing reads generated by Illumina HiSeq.
      Three out of four observed intra-sample variants caused an amino acid variation
      in C, NS2B, and NS5 genes. The C4279T variant located in the NS2B gene can
      indirectly affect the proteolytic activity of the NS3 protein. The sequence
      provided in this study might be useful for the epidemiological study of DENV-4.

PMID- 28767985
TI  - Surveillance of deaths caused by arboviruses in Brazil: from dengue to
      chikungunya.
AB  - Did death occur DUE TO dengue, or in a patient WITH dengue virus infection? It
      seems a matter of semantics, but in fact, it underscores how challenging it is to
      distinguish whether the disease contributed to death, or was itself the
      underlying cause of death. Can a death be attributed to chikungunya virus, when
      some deaths occur after the acute phase? Did the virus decompensate the
      underlying diseases, leading to death? Did prolonged hospitalisation lead to
      infection, resulting in the patient's progression to death? Were there iatrogenic
      complications during patient care? The dengue question, for which there has not
      yet been a definitive response, resurfaces prominently under the chikungunya
      surveillance scenario. We are facing an epidemic of a disease that seems to be
      more lethal than previously thought. The major challenge ahead is to investigate
      deaths suspected of occurring due to arbovirus infections and to understand the
      role of each infection in the unfavourable outcome.

PMID- 28767986
TI  - Mammographic density among indigenous women in forested areas in the state of
      Amapa, Brazil: a cross-sectional study.
AB  - CONTEXT AND OBJECTIVE:: There is no register of breast cancer cases among
      indigenous populations in Brazil. The objective here was to evaluate the
      association of clinical and demographic characteristics with mammographic density
      among indigenous women. DESIGN AND SETTING:: Cross-sectional analytical study
      conducted in indigenous territories in the state of Amapa, Brazil. METHODS::
      Women were recruited from three indigenous territories and underwent bilateral
      mammography and blood collection for hormonal analysis. They were interviewed
      with the aid of an interpreter. Mammographic density was calculated using
      computer assistance, and was expressed as dense or non-dense. RESULTS:: A total
      of 137 indigenous women were included in this study, with an average age of 50.4
      years, and an average age at the menarche of 12.8 years. Half (50.3%) of the 137
      participants had not reached the menopause at the time of this study. The women
      had had an average of 8.7 children, and only two had never breastfed. The average
      body mass index of the population as a whole was 25.1 kg/m2. The mammographic
      evaluation showed that 82% of women had non-dense breasts. The clinical
      characteristics associated with mammographic density were age (P = 0.0001),
      follicle-stimulating hormone (FSH) (P < 0.001) and estrogen levels (P < 0.01).
      CONCLUSIONS:: The majority of the indigenous women had non-dense breasts. Age,
      menopausal status and FSH and estrogen levels were associated with mammographic
      density.

PMID- 28767987
TI  - Are there differences in birth weight according to sex and associations with
      maternal exposure to air pollutants? A cohort study.
AB  - CONTEXT AND OBJECTIVE:: Several effects of exposure to air pollutants on human
      health are known. The aim of this study was to identify whether exposure of
      pregnant women to air pollutants contributes towards low birth weight and which
      sex is more affected. DESIGN AND SETTING:: Longitudinal study using data on
      newborns from mothers living in Sao Jose do Rio Preto (SP) who were exposed to
      air pollutants in 2012-2013. METHODS:: A hierarchical model on three levels was
      built using maternal and newborn variables and environmental concentrations of
      particulate matter, ozone and nitrogen dioxide in quartiles. Preterm new-borns,
      twins and newborns with birth defects were excluded and exposure windows of 30,
      60 and 90 days before delivery were considered. RESULTS:: 8,948 newborns were
      included: 4,491 males (50.2%) and 4,457 females (49.8%); 301 newborns presented
      low birth weight (3.4%). The mean weight differed between males (3281.0 g) and
      females (3146.4 g) (P < 0.001). Exposure to ozone was significantly associated
      with low birth weight in both sexes in the 30-day window (odds ratio, OR = 1.38)
      and 90-day window (OR = 1.48); and among females, in the 30-day window (OR =
      1.58) and 90-day window (OR = 1.59). Exposure to particulate matter had a
      paradoxical protective effect. No association was found among male newborns.
      CONCLUSIONS:: Female newborns showed greater susceptibility to maternal exposure
      to air pollutants. Studies on low birth weight in relation to maternal exposure
      to air pollutants should deal with males and females separately.

PMID- 28767988
TI  - Quality of diet plans for weight loss featured in women's magazines. A cross
      sectional descriptive study.
AB  - CONTEXT AND OBJECTIVE:: Brazil has the fifth largest population of obese
      individuals in the world. Women's magazines publish a large number of diet plans,
      and therefore the objective of this study was to assess the quality of these
      plans. DESIGN:: Cross-sectional descriptive study. METHODS:: We included the
      Brazilian women's magazines of highest circulation published between January and
      June 2014 that advertised diets for weight loss on their covers. We extracted the
      quantities of macro and micronutrients from each of these diet plans and compared
      these quantities with the World Health Organization nutritional guidelines for
      adult women. We also checked the total energy quantities of these plans, and any
      recommendations about water intake and physical activity. RESULTS:: We identified
      136 potentially eligible magazine issues; 41 were excluded and 95 issues of 6
      different magazines were included in the study. We found that 83.1 % of the plans
      had carbohydrate and fiber levels below the recommendations. On the other hand,
      the protein and saturated fatty acid levels were above the recommendations in
      97.8% and 95.7% of the plans, respectively; 75.7% of the diets had inadequate
      calcium levels and 70.5% had low iron levels. Only 30 plans specified the total
      daily quantity of dietary energy and in 53.3% of these, the information was
      inconsistent with our estimates; 20% of the plans had no recommendations on daily
      water intake and 37.5% did not give recommendations regarding physical activity
      practices. CONCLUSION:: The diet plans for weight loss featured in Brazilian
      women's magazines are of low quality.

PMID- 28767989
TI  - Report of a rare case of histiocytic necrotizing lymphadenitis with bilateral
      pleural effusion diagnosed via cervical lymph node biopsy.
AB  - CONTEXT: Histiocytic necrotizing lymphadenitis (HNL) is a rare disorder that is
      often benign and self-limiting. There have been reports of co-occurrence of HNL
      with other diseases, including systemic lupus erythematosus, hemophagocytic
      syndrome and antiphospholipid syndrome. CASE REPORT: Here, we report a case in
      which a patient experienced unexplained fever, swelling of the cervical lymph
      node and bilateral pleural effusion and was ultimately diagnosed with HNL based
      on results from a lymph node biopsy. After treatment with glucocorticoid, the
      patient regained normal body temperature, the swelling of the lymph nodes
      disappeared and the pleural effusion was reabsorbed. CONCLUSIONS: The
      pathogenesis of HNL remains unclear, and pleural effusion is rarely reported in
      HNL patients. We presented this case to improve diagnostic awareness of this
      condition among clinicians and help reduce the likelihood of misdiagnosis.

PMID- 28767990
TI  - Proportion of doctors who stayed in the state of Tocantins after finishing
      medical residency: preliminary results from a cross-sectional study.
AB  - CONTEXT AND OBJECTIVE: Few studies have assessed the impact of medical
      residencies on the public healthcare system. The aim here was to assess the
      number of specialists who remained in the state of Tocantins after finishing the
      medical residency program during the first two years of the first programs (2013
      and 2014). DESIGN AND SETTING: Cross-sectional and exploratory study conducted at
      the Federal University of Tocantins in Brazil. METHODS: All graduates of medical
      residency programs in Tocantins, of the years 2013 and 2014, were interviewed by
      telephone and e-mail between May and July 2014. RESULTS: Information was obtained
      from 37 graduates from medical residency. Seventeen (50.0%) were working in the
      state public healthcare system and only six (17.6%) in a municipal service in
      June 2014. Considering only the 24 doctors who had never worked in the state of
      Tocantins before their residency, it was observed that two who graduated in 2013
      (20.0%) and five who graduated in 2014 (35.7%), i.e. seven out of the total
      number (29.2%), had established their homes in Tocantins. CONCLUSIONS: The number
      of graduates from medical residency who stayed in the state of Tocantins in 2013
      and 2014 was small. However, this was related to the absence of other programs
      for continuation of the specialization. The state healthcare system was primarily
      responsible for employment of these doctors within public services. On the other
      hand, hiring by municipal services was extremely low.

PMID- 28767991
TI  - Analysis of quality of life among asthmatic individuals with obesity and its
      relationship with pulmonary function: cross-sectional study.
AB  - CONTEXT AND OBJECTIVE:: The combined effect of obesity and asthma may lead to
      significant impairment of quality of life (QOL). The aim here was to evaluate the
      prevalence of asthma among obese individuals, characterize the severity of
      impairment of quality of life and measure its relationship with pulmonary
      function. DESIGN AND SETTING:: Observational cross-sectional study in public
      university hospital. METHODS:: Morbidly obese individuals (body mass index > 40
      kg/m2) seen in a bariatric surgery outpatient clinic and diagnosed with asthma,
      were included. Anthropometric data were collected, the Standardized Asthma
      Quality of Life Questionnaire (AQLQ(S)) was applied and spirometry was performed.
      The subjects were divided into two groups based on the median of the score in the
      questionnaire (worse < 4 and better > 4) and were compared regarding
      anthropometric data and pulmonary function. RESULTS:: Among the 4791 individuals
      evaluated, 219 were asthmatic; the prevalence of asthma was 4.57%. Of these, 91
      individuals were called to start multidisciplinary follow-up during the study
      period, of whom 82 answered the questionnaire. The median score in the AQLQ(S)
      was 3.96 points and, thus, the individuals were classified as having moderate
      impairment of their overall QOL. When divided according to better or worse QOL,
      there was a statistically difference in forced expiratory flow (FEF) 25-75%, with
      higher values in the better QOL group. CONCLUSION:: The prevalence of asthma was
      4.57% and QOL was impaired among the asthmatic obese individuals. The worst QOL
      domain related to environmental stimuli and the best QOL domain to limitations of
      the activities. Worse QOL was correlated with poorer values for FEF 25-75%.

PMID- 28767992
TI  - Cognitive performance of premature infants: association between bronchopulmonary
      dysplasia and cognitive skills. Cross-sectional study.
AB  - CONTEXT AND OBJECTIVE:: Children born prematurely often have worse cognitive
      performance than those born at term regarding skills such as memory, attention
      and processing speed. Bronchopulmonary dysplasia may compromise cognitive
      development. The aims here were: a) To describe the cognitive performance of
      preterm infants with very low birth weight; b) To investigate its association
      with bronchopul-monary dysplasia adjusted for sociodemographic, neonatal and post
      neonatal factors. DESIGN AND SETTING:: Cross-sectional study developed in a
      public tertiary-care hospital. METHODS:: To evaluate cognition among 112
      children, we applied an intelligence scale (Wechsler scale). The average scores
      for children with and without bronchopulmonary dysplasia were compared across the
      fve domains of the scale. Associations with bronchopulmonary dysplasia were
      investigated for domains that showed signifcant diferences between the two
      groups. Associations between exposure and outcome were estimated via multivariate
      logistic regression. RESULTS:: There were no diferences in averages for the full
      scale intelligence quotient, verbal intelligence quotient, performance
      intelligence quotient and general language composite domains. The processing
      speed quotient was the only domain that presented a signifcant diference between
      the two groups (P = 0.02). Among the children with bronchopulmonary dysplasia,
      low full-scale intelligence quotient was observed in 28.1%. In the multivariate
      analysis, bronchopulmonary dysplasia (odds ratio: 3.1; 95conf-dence interval: 1.1
      8.7) remained associated with the outcome of processing speed quotient.
      CONCLUSION:: Bronchopulmonary dysplasia was an independent risk factor for
      alteration of the processing speed quotient.

PMID- 28767993
TI  - Physical activity in Brazil: lessons from ELSA-Brasil. Narrative review.
AB  - CONTEXT AND OBJECTIVE:: The Brazilian Longitudinal Study of Adult Health (ELSA
      Brasil) was conducted among civil servants at six higher education institutions
      located in six Brazilian state capitals. The objective of this review was to
      identify the publications produced within the scope of ELSA-Brasil that analyzed
      the participants' physical activity. DESIGN AND SETTING:: Review study using
      baseline data from ELSA-Brasil. METHODS:: Narrative review of Brazilian studies
      on physical activity produced using data from ELSA-Brasil participants. RESULTS::
      The prevalence of leisure-time physical activity (LTPA) among ELSA-Brasil
      participants was low (44.1% among men and 33.8% among women). The main factors
      associated were social (higher schooling and family income), environmental
      (living in places with conditions and opportunities for physical activity) and
      individual (not being obese, being retired, not smoking and positive perception
      of body image). The perception of facilities for walking in the neighborhood was
      positively associated with both LTPA and commuting-related physical activity. An
      active lifestyle was a protective factor against several cardiometa-bolic
      variables (hypertension, diabetes, lipid abnormalities and cardiovascular risk
      over the next 10 years). Comparison between LTPA and commuting-related physical
      activity showed that only LTPA had a protective effect against arterial
      hypertension. CONCLUSIONS:: The prevalence of physical activity among ELSA-Brasil
      participants was low. The main determinants were social, environmental and
      personal. LTPA had a greater protective efect on cardio-metabolic outcomes than
      did commuting-related physical activity.

PMID- 28767994
TI  - Sociodemographic characteristics of women in a public hospital in Campinas who
      underwent legal abortion due to sexual violence: cross-sectional study.
AB  - CONTEXT AND OBJECTIVE:: Sexual violence is increasingly frequent worldwide. The
      aim here was to evaluate the sociodemographic and psychological characteristics
      of women who requested legal abortion, at a public healthcare service, after
      sufering sexual violence. DESIGN AND SETTING:: Retrospective descriptive study on
      131 women who underwent legal abortion at the University of Campinas between 1994
      and 2014, consequent to sexual violence. METHODS:: The sociodemographic and
      psychological characteristics of women who were victims of sexual violence were
      evaluated from their medical records. The tests used to evaluate possible
      associations were the chi-square and/or Fisher's exact test. RESULTS:: The
      women's mean age was 23 +/- 9.2 years; 77.9% were white and 71.8% were single;
      32.8% were students and 58.6% had employment outside of their homes. The majority
      reported that they did not know the aggressor (62.3%), but among the adolescents,
      58% of the aggressors were known. The majority asked for abortion up to the 12th
      weeks of gestation (63.4%). Only 2.3% presented curettage complications. The
      psychological situation most frequently encountered was determined, in 34.4% of
      the cases before the abortion; and good in 32.8% after the abortion.
      CONCLUSIONS:: There was greater occurrence of sexual violence among students and
      women who worked outside. Among the students, most of these were adolescents and
      had no previous sexual life. The teenagers were raped by a known aggressor.

PMID- 28767996
TI  - ?

PMID- 28767995
TI  - Wealth inequality and weak primary care in the city of Sao Paulo: ingredients for
      a dysfunctional and ineffective healthcare system.

PMID- 28767997
TI  - [The administrative function of the nurse in the newborn unit].
AB  - Considerations are made about the neonatal service of the hospital with special
      attention to the newborn unit. The authors describe the role of the nurse as a
      most valuable element of the functional group and emphasize her administrative
      function in the newborn.

PMID- 28767998
TI  - [Nursing problems affecting patients in peritoneal dialysis].
AB  - The authors try to identify the main nursing problems affecting patients in
      peritoneal dialysis. They intend, also, to find some stand points in order to
      determine, in a next survey, a treatment based on more accurate data. This study
      show that for a large number of the patients, there is a mutual relation between
      the problems perceived and the expectancy of nursing intervention.

PMID- 28767999
TI  - [Nursing care of the drug addict patient].
AB  - The authors describe types of drug addiction, behavior of the drug addict patient
      and the role of nursing personnel in dealing with them. They also mention some
      prophylactic measures in the fight off drug addiction.

PMID- 28768000
TI  - [Perception of Intensive Care Unit patients - problems felt and expectations in
      relation of nursing care].
AB  - A survey made with adult patients, submitted to cardiac surgery, who stayed in
      Intensive Care Unit (ICU) between 24 to 72 hours. The main point of the survey
      was to verify the most frequent problems felt by the patients in ICU and their
      expectations in relation to nursin care. It was found that, the majority of the
      problems felt and of the expectations related to nursing assistance belong in the
      basic area, more so than in the technical area.

PMID- 28768001
TI  - [Main physiological problems presented by patients with respective nursing
      prescription].
AB  - In this paper, the authors relate the main physiological problems identified by
      nurses in myocardial infarction patients. Following, they present which were the
      nursing prescriptions to be adopted by nursing personnel, facing such problems.

PMID- 28768002
TI  - [Nursing assistance to hospitalized children instraightened circunstances].
AB  - In this article, the first of a series, there were related two experiences of
      nursing students in pediatrics, helping the hospitalized children to cope with
      difficult circunstances, as to say, the inserting of a naso-gastric tube.

PMID- 28768003
TI  - [The community nursing in the nursing curriculum (part II)].
AB  - The first part of this article contained the basic concepts on health, public
      health and community nursing. This part includes the problems found in community
      health services and presents suggestions about the functions of the public health
      nurse.

PMID- 28768004
TI  - [Dispneic patient: specific expectancies about the nursing assistance (part
      III)].
AB  - The author assesses the specific expectancies of the dispneic patient related to
      nursing assistance and nursing attendance. The coincidence of data obtained from
      informations given by both the patient and the nursing personnel is also studied.

PMID- 28768006
TI  - ?

PMID- 28768007
TI  - ?

PMID- 28768005
TI  - [Contribution of the nurse in the fight against schistosomosis in hospitals].
AB  - The authors, who are undergraduate nursing students, describe one of their
      activities in their field experience in Nursing Administration. They give the
      description of a plan they made for early detection of schistosomosis in family
      members of patients with the disease; implementation of the plan; and orientation
      and treatment of the ones with positive laboratory results.

PMID- 28768008
TI  - DISCURSO PRONUNCIADO PELO PROFESSOR CARLOS DA SILVA LACAZ NA ESCOLA DE ENFERMAGEM
      DA UNIVERSIDADE DE SAO PAULO, POR OCASIAO DO ENTERRO DA PROFESSORA WANDA DE
      AGUIAR HORTA, NO DIA 16 DE JUNHO DE 1981.

PMID- 28768009
TI  - [Clinical teaching: its importance in nurses's training].
AB  - The authors describe the clinical teaching as an essential element in nurses's
      training, giving its characteristics, advantages and requirements.

PMID- 28768010
TI  - [Nursing care of patients with agitation and agressiveness manifestations].
AB  - The authors describe the nursing care of patients with agitation and
      aggressiveness manifestations, in order to preserve their physical and psychic
      integrity, to protect the integrity of those around them and to help the patient
      control his own behavior.

PMID- 28768011
TI  - [Intracranial pressure monitoring].
AB  - Basic aspects of intracranial pressure monitoring are presented. They are
      necessary for to effective action of the nurse who looks after patients submitted
      to this procedure.

PMID- 28768012
TI  - [Setting limits as a therapeutic measure in the nurse-patient relationship].
AB  - The authors discuss the importance and the necessity of stablishing limits as
      therapeutic tool in the nurse-patient relationship. They review the literature on
      the subject and outline the steps and techniques recommended in the application
      of such tools.

PMID- 28768013
TI  - [Fundamentals of the nursing care for the patients with meningococic disease].
AB  - Analysis of the patients problems with meningococic disease and the basic mursing
      procedure in the control of that disease.

PMID- 28768014
TI  - [The use of nontherapeutic patterns of communication].
AB  - Comparative study between two groups of students of the nursing technician
      program, to verify their use of nontherapeutic patterns of communication, during
      interaction with psychiatric patients.

PMID- 28768015
TI  - [The role of the nursing group in the primary health care].
AB  - The author relates the activities developed by the nursing personnel at the
      primary care level of basic health services. She also describes comments some
      obstacles to be overcome for the effective participation of this personnel in
      first level of the health care offered to the population.

PMID- 28768017
TI  - [Teaching of undergraduate Pedriatric Nursing].

PMID- 28768016
TI  - [Manoeuvre of compression of the cervical groove].
AB  - Study about the manoeuvre of compression of the cervical groove, in parturient
      women, as mean of diagnosis of loops of the umbilical cord, around the fetal
      neck. The population was constituted by 132 parturients (58 primiparous and 74
      multiparous), with a single fetus in cephalic presentation, during the stage of
      dilatation, with unbroken amniotic membranes and no clinical signs of fetal
      suffering. The data obtained give evidence of the efficiency of the manoeuvre for
      dettecting the presence of loops of the umbilical cord around the fetal neck.

PMID- 28768018
TI  - [Social aspects of nursing].

PMID- 28768019
TI  - [Considerations on the profile of the nurse].

PMID- 28768020
TI  - [CRITICAL ANALYSIS OF THE PROBLEMATIC OF THE ADEQUACY BETWEEN THE FORMER AND THE
      SERVICE INSTITUATION IN RESPECT OF THE ROLE EXPECTATION OF THE OPERATING ROOM
      NURSE.]

PMID- 28768021
TI  - ?

PMID- 28768022
TI  - ?

PMID- 28768023
TI  - [Changing the curriculum of the undergraduate program at the Ribeirao Preto
      School of Nursing, University of Sao Paulo].
AB  - This paper presents the initial considerations on possible changes in the
      curriculum of the undergraduate program. The three first steps of the technical
      model of the curriculum plan recommended by Saul (1971) were studied, i.e. the
      diagnosis of the needs, educational objectives, and selection and organization of
      the contents. Some philosophical aspects of nursing education born out of the
      needs felt by teachers and pupils were discussed. Such aspects were basic in the
      determination of the nurse's function. Based on the nurse's function, the
      educational objectives of the curriculum were established. The next step was the
      listing of the contents necessary to the fulfillment of the objectives. This work
      is to be continued.

PMID- 28768024
TI  - [Smoking in schools of nursing].
AB  - A study was made among students and instructors of three schools of nursing at
      Sao Paulo City, Brazil, on number of smokers, non smokers and previous smokers
      and the causes that led them to start smoking as well as to withdraw from the
      habit. In a population of 636 studients the authors found 24.1% smokers, 68.5%
      non smokers, 7.4% previous smokers. The percentage of 117 instructors were 23.1%,
      62.4% and 14.5% respectively. The reason for start smoking most frequently
      mentioned by both groups was curiosity (35.2% and 28.2% respectively). For
      leaving the habit was conscience of damage to health (72.5% and 65.2%). For the
      non smokers this was the main reason for never starting the habit. The authors
      studied also the age of start smoking, number of cigarettes smoked per day. The
      outside influences for smoking or not orientation of others about the damages of
      smoking to health were also considered.

PMID- 28768025
TI  - [Iatrogeny: implications for nursing care].
AB  - The authors describe the theoretical aspects of iatrogeny which are due to drugs,
      patient reactions, and failure in the application of drugs by nursing personnel.
      They discuss nursing intervention on primary, secondary and tertiary level of
      prevention and they alert the nurses of the importance of introducing the topic
      in nursing education programs.

PMID- 28768026
TI  - [Students' evaluation of a new teaching methodology of Pediatric Nursing].
AB  - This article includes some considerations about teaching Pediatric Nursing to
      undergraduate students so as to justify instructors' change in attitude toward
      the teaching-learning process and focus evaluation made by six groups of students
      on the new method employed. On the whole, the students' attitude was more
      positive than when the traditional method was employed; they were more interested
      in Pediatric Nursing and showed better understanding of children's needs.

PMID- 28768027
TI  - [Medical-surgical nursing integration evaluated by students and instructor].
AB  - Students and "instructors" opinions were collected on the teaching of the Medical
      Nursing I program (for undergraduates) and on their experience on the
      respiratory, cardiologic, neurological, digestive and renal hospital units. 63.2%
      of the students felt the objectives had been reached, 77.2% that there was "some
      uniformity" of teaching each unit, that their hospital experience had been
      satisfactory in both quality and quantity in all units but in the Neurology units
      (one of these units was being remodeled and could not be used), that bibliography
      was sufficcient and adequate (73.7%), that there had been correlation between
      theory and practice in all units, and that evaluation had been satisfactory.
      Evaluation by instructors of some itens was not very different.

PMID- 28768028
TI  - [Spreading out Brazilian nursing scientific knowledge].
AB  - The authors list the vehicles used by authors of scientific literature to have
      their work known, particularly journals, and the number of nursing journals
      indexed in the Cumulative Index to Nursing & Allied Health Literature (1981).
      Brazil has 3, which is higher than many countries but very low compared to 8 in
      Canada, 10 in Japan, 139 in USA. Thesis written by Brazilian nurses are mentioned
      as well as the existing catalogues where they are registered. The authors also
      discuss oral information given out a conventions, workshops, seminars, etc and
      emphasize the difficulties felt by Brazilian nurses to have access to nursing
      literature.

PMID- 28768030
TI  - ?

PMID- 28768029
TI  - [The noise made by the equipments used in operating-rooms: preliminary study by
      the physiological and psychological alterations in the components of the surgical
      team and the patient].
AB  - It was studied in global values and octave band, on the L and A scales, the usual
      noise of three operating-rooms, in two hospitals in Sao Paulo. The same study had
      been done with the noises made by the following equipments, that are normaly used
      in operating-rooms: eletric Valleylab, Emai, Bovie, Burdick bistouries; Takaoka,
      Narcofolex, Aga, Oftec respirators; Takaoka, Medap, Card, Oftec aspirators;
      Dremel, Kaltembach und Voigt drills; eletric Bone Stryker Saw and, FUNBEC
      cardioscopic. It was confronted, yet, the noise made by aparatus of different
      trade marks, but, with the same functions, like: respirators, aspirators, eletric
      bistuories and eletric drills. It was stipulated the average additions of the
      noises made by five equipments that work simultaneously. The results of the tests
      proved that the noise, in the studied operating-rooms, is inferior of the maximum
      level preconized for hospitals. The obtained results, permit to conclude that the
      noise made by the studied apparatus is not sufficient to cause deafness in the
      components of the surgical team or in the patient, but it is sufficient to cause
      physiological and psychological alterations in those ones.

PMID- 28768031
TI  - ?

PMID- 28768032
TI  - [Instrument to analyse periodicals of nursing].
AB  - Studies about spreading of knowledge in nursing are recent. In order to
      contribute to the study of the nursing literature in Brazil, it was developed a
      model of instrument to analyse periodicals. The instrument was tested in a
      nursing periodical and it was found to be effective in stablishing who writes,
      what is written and even to relate the papers with present state of health and
      the historical evolution of the profession.

PMID- 28768033
TI  - [Iatrogeny in nursing].
AB  - The authors of this study, considering that the main cause of iatrogeny in
      nursing lies in the lack of the nurses theoretical preparation, analysed the
      knowledge of 51 nurses in the preparation of medications. They tried to correlate
      this knowledge with the length of undergraduate program and with previous
      hospital experience. No correlation was found.

PMID- 28768034
TI  - [Nursing assistance in tracheostomy: a teaching experience].
AB  - The authors applied the teaching experience with the intention of make contact
      with students of nursing's graduation and patients with tracheostomy, yonder
      develop them theoretical-practical's teaching about the technic of tracheostomy's
      secretions suction and propitiate them opportunity to apply the above mentioned
      technic, independent or not of assume during the period of training these
      patienfs assistance. The authors concluded that the experience was valid and that
      planed's periods to theore-tical's studies and practical's tasks about the
      technic of tracheostomy's secretions suction are importants to offer to the
      students contact with the patient and this method, indispensable to his wellbeing
      and security.

PMID- 28768035
TI  - [Nursing care to patient on electroconvulsive therapy].
AB  - Eletric convulsive shock therapy has become a controversial topic in psychiatric
      services. Patients continue to have electroconvulsive therapy. The team nursing
      has seen the treatment as just another task. In this paper the authors present
      how the nurse can help the patient who is submitted to electroconvulsive therapy.

PMID- 28768037
TI  - ?

PMID- 28768036
TI  - [Therapeutic relationship: account of an experience].
AB  - The author, a undergraduate nursing student, presents a nurse-patient therapeutic
      relationship process. She and the patient by the sequential phases and the use of
      therapeutic communication skills met their's goals in the therapeutic process.

PMID- 28768038
TI  - [Open University and its applicability in Nursing].
AB  - The article covers aspects of a educational system, called Open University, which
      began in England in 1963. Its structure, organization and evaluation are
      presented, as well as some attempts to implement the methodology in Brazil. The
      authors suggest that the idea behind the Open University - dissemination of
      knowledge - should be incorporated by nurses, in order to encourage them towards
      continuing education, and indicate some organizations through which such programs
      could be known and extended throughout the country.

PMID- 28768039
TI  - [Feeling the worth of significative experiences in learning process: experiences
      of a nurse with two hospitalized children].
AB  - This study describes two experiences of a nurse with hospitalized children. The
      first includes a description an explanation of the behavior of a child recently
      admitted to the hospital, based on the nurse's observations. The second
      experience involves the use of therapeutic play in a specific nurse-patient
      relationship, with observations of subsequent changes in the child's behavior.
      The author describes how these two experiences enhanced her ability to give and
      teach pediatric nursing care.

PMID- 28768040
TI  - [Home visit plan: a model].
AB  - The authors propose a model of an operational and dynamic plan for home visit
      taking into account the wide-ranging way in which the subject should be taught.
      This paper also provides a detailed guide with the necessary information for the
      adequate use of such plan. The use of the plan does not exclude the relevance of
      previous knowledge about the home visit methodology and particularly of the way
      of relationship between nurse and family.

PMID- 28768041
TI  - [Research in maternal-child nursing].
AB  - By way of a short bibliographical revision, these authors outline some general
      directives for research in the maternal-child area of nursing. They identify
      existing research projects in this area, which are published in three
      bibliographical sources. They depict the predominance of emphasis in these
      projects - be it nursing assistance, administration or teaching. The authors also
      analyse the tendencies that these current investigations seem to be following.

PMID- 28768042
TI  - [Restricted visiting for hospitalized children: a barrier to mother-child
      interaction].
AB  - The author presents data concerning mother-child relationship promotion, results
      of her observations in three pediatric hospitals. Verificating that the visit
      represents the sole opportunity for not breaking mother-child contact, the author
      discusses some effects of the restricted visit upon mother-child relationship,
      pointing out the need of including the mother in the child's care.

PMID- 28768043
TI  - [Nursing communication tool. A study to introduce a written model for
      communication between nursing staff of the surgical units and the operating
      rooms].
AB  - A study to introduce a nursing communication toot to make easier the continuity
      of nursing care of the surgical patient in the pre, per and postoperative
      periods. The communication tool consists in two parts: preoperative and
      peroperative notes form. This tool was aplied to 327 patients undergoing surgical
      treatment who were interned in three general surgical units and in three
      specialized units in a general hospital. The application of the tool was made by
      nursing staff of the surgical units and the operating room of the hospital. It
      was verified, by the analysis of results, that the frequency of the filling-in
      items on the preoperative form was higher than 83%, above the 70% established in
      this present study. The percentage of items registered on the peroperative form
      was above 85%, excepting pulse rate and blood pressure that showed less than 70%.
      The frequency of the filling-in of the items on the two forms, preoperative and
      peroperative, was analyzed separately for each six surgical units. The percentual
      variation of the filling-in was between 83 and 100% which makes possible the
      inference that this nursing communication tool is certainly applicable to
      patients undergoing general specialized surgery.

PMID- 28768044
TI  - [Study about collection of urine for bacteriologic culture].
AB  - This study was made in the City of Sao Paulo, in 30 hospitals with the objective
      of to identify and classify the procedures of collecting urine for bacteriologic
      study. The data's collect has been realized based on a record prepared for a
      systematic observation directly connected to a system interpretative of
      categories ("Good", "Fair" and "Poor") applied to all procedures. The results
      obtained have been presented in the tables distributed in the absolute end
      relative frequencies, grouped and classified by categories. The conclusions where
      in accordance to the specific objectives initially proposed and has been
      classified under the interpretative systems of the categories previously defined
      and adressed to the research.

PMID- 28768045
TI  - Examining Factors that Influence the Existence of Heinrich's Safety Triangle
      Using Site-Specific H&S Data from More than 25,000 Establishments.
AB  - In the 1930s, Heinrich established one of the most prominent and enduring
      accident prevention theories when he concluded that high severity occupational
      safety and health (OSH) incidents are preceded by numerous lower severity
      incidents and near misses. Seventy-five years of theory expansion/interpretation
      includes two fundamental tenets: (1) the ratio of lower to higher severity
      incidents exists in the form of a "safety-triangle" and (2) similar causes
      underlie both high and low severity events. Although used extensively to inform
      public policy and establishment-level health and safety priorities, recent
      research challenges the validity of the two tenets. This study explored the
      validity of the first tenet, the existence of the safety triangle. The advantage
      of the current study is the use of a detailed, establishment-specific data set
      that evaluated over 25,000 establishments over a 13-year time period, allowing
      three specific questions to be explored: (1) Are an increased number of lower
      severity incidents at an establishment significantly associated with the
      probability of a fatal event over time? (2) At the establishment level, do the
      effects of OSH incidents on the probability of a fatality over time decrease as
      the degree of severity decreases-thereby taking the form of a triangle? and (3)
      Do distinct methods for delineating incidents by severity affect the existence of
      the safety triangle form? The answer to all three questions was yes with the
      triangle form being dependent upon how severity was delineated. The implications
      of these findings in regard to Heinrich's theory and OSH policy and management
      are discussed.

PMID- 28768047
TI  - "Being a Therapist Doesn't Exclude You From Real Life": Family Therapists'
      Beliefs and Barriers to Political Action.
AB  - A crucial and overlooked facet of social justice in family therapy is political
      and policy advocacy. Family therapists have unique insight into how social
      policies and political discourse shapes clients' lives and the life of our
      profession. Such knowledge can inform policymakers and political debate, yet few
      family therapists are trained to engage in political action. In this randomized,
      national survey of licensed family therapists' (N = 174), we explore beliefs
      about and barriers to engagement in political and policy processes. The findings
      suggest that there are significant barriers and uncertainties surrounding family
      therapists' engagement, including time, feelings of efficacy, and interest. Given
      these barriers we discuss practical suggestions for clinicians and family therapy
      training programs.

PMID- 28768048
TI  - Optimizing the Accuracy and Computational Cost in Theoretical Squaramide
      Catalysis: The Henry Reaction.
AB  - This study represents the first example where the accuracy of different
      combinations of density functional theory (DFT) methods and basis sets have been
      compared in squaramide catalysis. After an optimization process of the precision
      obtained and the computational time required in the computational calculations,
      highly precise results were achieved compared to the experimental outcomes while
      requiring the least amount of time possible. Here, we have explored
      computationally and experimentally the mechanism of the squaramide-catalyzed
      Henry reaction. This is a complex reaction of about 100 atoms and a great number
      of diverse non-covalent interactions. Moreover, this research is one of the
      scarce examples where the organocatalyst acts in a trifunctional manner and is
      the first investigation in which a trifunctional squaramide catalyst has been
      employed. Functional omegaB97X-D showed the best results when used with different
      versions of the 6-311 basis sets, leading to highly accurate calculations of the
      outcomes of the Henry reaction when using nine aldehydes with different
      structural characteristics. Furthermore, in these relatively large systems, the
      use of a split-valence triple-zeta basis set saves a large amount of time
      compared with using larger basis sets that are sometimes employed in
      organocatalytic studies, such as the TZV and Def2TZV basis set families.

PMID- 28768046
TI  - Carbon monoxide released from its pharmacological donor,
      tricarbonyldichlororuthenium (II) dimer, accelerates the healing of pre-existing
      gastric ulcers.
AB  - BACKGROUND AND PURPOSE: Carbon monoxide (CO), a gaseous mediator produced by haem
      oxygenases (HOs), has been shown to prevent stress-, ethanol-, aspirin- and
      alendronate-induced gastric damage; however, its role in gastric ulcer healing
      has not been fully elucidated. We investigated whether CO released from
      tricarbonyldichlororuthenium (II) dimer (CORM-2) can affect gastric ulcer healing
      and determined the mechanisms involved in this healing action. EXPERIMENTAL
      APPROACH: Gastric ulcers were induced in Wistar rats by serosal application of
      acetic acid. Animals received 9 days of treatment with RuCl3 [2.5 mg.kg-1
      intragastrically (i.g.)], haemin (5 mg.kg-1 i.g.), CORM-2 (0.1-10 mg.kg-1 i.g.)
      administered alone or with zinc protoporphyrin IX (ZnPP, 10 mg.kg-1 i.g.), 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 mg.kg-1 i.g.), NG -nitro-l
      arginine (l-NNA, 15 mg.kg-1 i.g.), indomethacin (5 mg.kg-1 i.g.) or glibenclamide
      (10 mg.kg-1 i.g.). Gastric ulcer area and gastric blood flow (GBF) were assessed
      planimetrically, microscopically and by laser flowmeter respectively. Gastric
      mRNA/protein expressions of EGF, EGF receptors, VEGFA, HOs, nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2), COX-2, hypoxia-inducible factor (HIF)-1alpha
      and pro-inflammatory iNOS, IL-1beta and TNF-alpha were determined by real-time
      PCR or Western blots. KEY RESULTS: CORM-2 and haemin but not RuCl3 or ZnPP
      decreased ulcer size while increasing GBF. These effects were reduced by ODQ,
      indomethacin, l-NNA and glibenclamide. CORM-2 significantly decreased the
      expression of pro-inflammatory markers, Nrf2/HO1 and HIF-1alpha, and up-regulated
      EGF. CONCLUSIONS AND IMPLICATIONS: CO released from CORM-2 or endogenously
      produced by the HO1/Nrf2 pathway accelerates gastric ulcer healing via an
      increase in GBF, an up-regulation in EGF expression and down-regulation of the
      inflammatory response.

PMID- 28768049
TI  - Hazard Analysis and Safety Requirements for Small Drone Operations: To What
      Extent Do Popular Drones Embed Safety?
AB  - Currently, published risk analyses for drones refer mainly to commercial systems,
      use data from civil aviation, and are based on probabilistic approaches without
      suggesting an inclusive list of hazards and respective requirements. Within this
      context, this article presents: (1) a set of safety requirements generated from
      the application of the systems theoretic process analysis (STPA) technique on a
      generic small drone system; (2) a gap analysis between the set of safety
      requirements and the ones met by 19 popular drone models; (3) the extent of the
      differences between those models, their manufacturers, and the countries of
      origin; and (4) the association of drone prices with the extent they meet the
      requirements derived by STPA. The application of STPA resulted in 70 safety
      requirements distributed across the authority, manufacturer, end user, or drone
      automation levels. A gap analysis showed high dissimilarities regarding the
      extent to which the 19 drones meet the same safety requirements. Statistical
      results suggested a positive correlation between drone prices and the extent that
      the 19 drones studied herein met the safety requirements generated by STPA, and
      significant differences were identified among the manufacturers. This work
      complements the existing risk assessment frameworks for small drones, and
      contributes to the establishment of a commonly endorsed international risk
      analysis framework. Such a framework will support the development of a holistic
      and methodologically justified standardization scheme for small drone flights.

PMID- 28768050
TI  - Gastric perforation by stiff guidewire in Danis stent assembly.

PMID- 28768051
TI  - Total Synthesis of the Schisandraceae Nortriterpenoid Rubriflordilactone A.
AB  - Full details of the total synthesis of the Schisandraceae nortriterpenoid natural
      product rubriflordilactone A are reported. Palladium- and cobalt-catalyzed
      polycyclizations were employed as key strategies to construct the central
      pentasubstituted arene from bromoendiyne and triyne precursors. This required the
      independent assembly of two AB ring aldehydes for combination with a common diyne
      component. A number of model systems were explored to investigate these two
      methodologies, and also to establish routes for the installation of the
      challenging benzopyran and butenolide rings.

PMID- 28768053
TI  - Textural pattern classification for oral squamous cell carcinoma.
AB  - Despite being an area of cancer with highest worldwide incidence, oral cancer yet
      remains to be widely researched. Studies on computer-aided analysis of
      pathological slides of oral cancer contribute a lot to the diagnosis and
      treatment of the disease. Some researches in this direction have been carried out
      on oral submucous fibrosis. In this work an approach for analysing abnormality
      based on textural features present in squamous cell carcinoma histological slides
      have been considered. Histogram and grey-level co-occurrence matrix approaches
      for extraction of textural features from biopsy images with normal and malignant
      cells are used here. Further, we have used linear support vector machine
      classifier for automated diagnosis of the oral cancer, which gives 100% accuracy.

PMID- 28768052
TI  - Cardioprotective effects of 5-hydroxymethylfurfural mediated by inhibition of L
      type Ca2+ currents.
AB  - BACKGROUND AND PURPOSE: The antioxidant 5-hydroxymethylfurfural (5-HMF) exerts
      documented beneficial effects in several experimental pathologies and is
      currently tested as an antisickling drug in clinical trials. In the present
      study, we examined the cardiovascular effects of 5-HMF and elucidated the mode of
      action of the drug. EXPERIMENTAL APPROACH: The cardiovascular effects of 5-HMF
      were studied with pre-contracted porcine coronary arteries and rat isolated
      normoxic-perfused hearts. Isolated hearts subjected to ischaemia/reperfusion
      (I/R) injury were used to test for potential cardioprotective effects of the
      drug. The effects of 5-HMF on action potential and L-type Ca2+ current (ICa,L )
      were studied by patch-clamping guinea pig isolated ventricular cardiomyocytes.
      KEY RESULTS: 5-HMF relaxed coronary arteries in a concentration-dependent manner
      and exerted negative inotropic, lusitropic and chronotropic effects in rat
      isolated perfused hearts. On the other hand, 5-HMF improved recovery of inotropic
      and lusitropic parameters in isolated hearts subjected to I/R. Patch clamp
      experiments revealed that 5-HMF inhibits L-type Ca2+ channels. Reduced ICa,L
      density, shift of ICa,L steady-state inactivation curves toward negative membrane
      potentials and slower recovery of ICa,L from inactivation in response to 5-HMF
      accounted for the observed cardiovascular effects. CONCLUSIONS AND IMPLICATIONS:
      Our data revealed a cardioprotective effect of 5-HMF in I/R that is mediated by
      inhibition of L-type Ca2+ channels. Thus, 5-HMF is suggested as a beneficial
      additive to cardioplegic solutions, but adverse effects and contraindications of
      Ca2+ channel blockers have to be considered in therapeutic application of the
      drug.

PMID- 28768054
TI  - HCV and nonhepatic malignancy: Is pre-emptive direct-acting antiviral therapy
      indicated prior to treatment?

PMID- 28768055
TI  - Harnessing CXCR4 antagonists in stem cell mobilization, HIV infection, ischemic
      diseases, and oncology.
AB  - CXCR4 antagonists (e.g., PlerixaforTM ) have been successfully validated as stem
      cell mobilizers for peripheral blood stem cell transplantation. Applications of
      the CXCR4 antagonists have heralded the era of cell-based therapy and opened a
      potential therapeutic horizon for many unmet medical needs such as kidney injury,
      ischemic stroke, cancer, and myocardial infarction. In this review, we first
      introduce the central role of CXCR4 in diverse cellular signaling pathways and
      discuss its involvement in several disease progressions. We then highlight the
      molecular design and optimization strategies for targeting CXCR4 from a large
      number of case studies, concluding that polyamines are the preferred CXCR4
      binding ligands compared to other structural options, presumably by mimicking the
      highly positively charged natural ligand CXCL12. These results could be further
      justified with computer-aided docking into the CXCR4 crystal structure wherein
      both major and minor subpockets of the binding cavity are considered functionally
      important. Finally, from the clinical point of view, CXCR4 antagonists could
      mobilize hematopoietic stem/progenitor cells with long-term repopulating capacity
      to the peripheral blood, promising to replace surgically obtained bone marrow
      cells as a preferred source for stem cell transplantation.

PMID- 28768056
TI  - Scaling and Sustaining Effective Early Childhood Programs Through School-Family
      University Collaboration.
AB  - We describe the development, implementation, and evaluation of a comprehensive
      preschool to third grade prevention program for the goals of sustaining services
      at a large scale. The Midwest Child-Parent Center (CPC) Expansion is a multilevel
      collaborative school reform model designed to improve school achievement and
      parental involvement from ages 3 to 9. By increasing the dosage, coordination,
      and comprehensiveness of services, the program is expected to enhance the
      transition to school and promote more enduring effects on well-being in multiple
      domains. We review and evaluate evidence from two longitudinal studies (Midwest
      CPC, 2012 to present; Chicago Longitudinal Study, 1983 to present) and four
      implementation examples of how the guiding principles of shared ownership,
      committed resources, and progress monitoring for improvement can promote
      effectiveness. The implementation system of partners and further expansion using
      "Pay for Success" financing shows the feasibility of scaling the program while
      continuing to improve effectiveness.

PMID- 28768057
TI  - Memory integration in humans with hippocampal lesions.
AB  - Adaptive behavior frequently depends on inference from past experience. Recent
      studies suggest that the underlying process of integrating related memories may
      depend on interaction between hippocampus and prefrontal cortex. Here, we
      investigated how hippocampal damage affects memory integration. Subjects with
      mediotemporal lesions and healthy controls learned a set of overlapping AB- and
      BC-associations (object-face- and face-object pairs) and were then tested for
      memory of these associations ("direct" trials) and of inferential AC-associations
      ("indirect" trials). The experiment consisted of four encoding/retrieval cycles.
      In direct trials, performance of patients and controls was similar and stable
      across cycles. By contrast, in indirect trials, patients and controls showed
      distinct patterns of behavior. Whereas patients and controls initially showed
      only minor differences, controls increased performance across subsequent cycles,
      while patient performance decreased to chance level. Further analysis suggested
      that this deficit was not merely a consequence of impaired associative memory but
      rather resulted from an additional hippocampal contribution to memory
      integration. Our findings further suggest that contextual factors modulate this
      contribution. Patient deficits in more complex memory-guided behavior may depend
      on the flexible interaction of hippocampus-dependent and -independent mechanisms
      of memory integration.

PMID- 28768058
TI  - Prenatal influence of congenital heart defects on trajectories of cortical
      folding of the fetal brain using three-dimensional ultrasound.
AB  - OBJECTIVE: The objective of the study is to investigate the prenatal influence of
      congenital heart defects (CHD) on trajectories of fetal cortical folding using
      three-dimensional ultrasound (3D US). METHOD: We included 20 CHD fetuses and 193
      controls for studying the fetal brain at 22, 26 and 32 weeks' gestational age
      (GA). The Sylvian, insula and parieto-occipital fissure (POF) depths were
      measured using 3D US, and reliability was evaluated. Doppler indices of the
      umbilical artery and middle cerebral artery were measured to calculate the
      cerebro-placental ratio. Associations between CHD and cortical folding were
      estimated using linear mixed models. RESULTS: Brain fissure measurements were
      successful in over 80% of 3D US scans, except for the POF at 32 weeks' GA (65%).
      All measurements showed a good reliability (intraclass correlation coefficients >
      0.84). Growth trajectories of the left insula depth (beta = -2.753, 95% CI = 
      5.375; -0.130, p = 0.040) and right POF (beta = -3.762, 95% CI = -7.178; -0.346,
      p = 0.031) were decreased in CHD compared with controls, whereas growth rates
      were increased (beta = 0.014, 95% CI = 0.001; 0.027, p = 0.036 and beta = 0.024,
      95% CI = 0.007; 0.041, p = 0.006). In contrast to controls, we found no
      associations between cerebro-placental ratio and cortical folding in CHD.
      CONCLUSION: Fetal cortical folding can be evaluated reliably by measuring brain
      fissure depths. Trajectories of cortical folding between 22 and 32 weeks' GA seem
      to be influenced by CHD. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28768059
TI  - (-)-Epicatechin rescues the As2 O3 -induced HERG K+ channel deficiency possibly
      through upregulating transcription factor SP1 expression.
AB  - (-)-Epicatechin (EPI) has beneficial effects on the cardiovascular disease. The
      human ether-a-go-go-related gene (HERG) potassium channel is crucial for
      repolarization of cardiac action potential. Dysfunction of the HERG channel can
      cause long QT syndrome type 2 (LQT2). Arsenic trioxide (As2 O3 ) has shown
      efficacy in the treatment of acute promyelocytic leukemia. However, As2 O3 can
      induce the deficiency of HERG channel and cause LQT2. In this study, we examined
      whether EPI could rescue the As2 O3 -induced HERG channel deficiency. We found
      that 3 MUM EPI obviously increased protein expression and current of HERG
      channel. EPI was able to recover the protein expression and current of HERG
      channel disrupted by As2 O3 . EPI was able to increase the expression of SP1
      protein and recover the expression of SP1 protein disrupted by As2 O3 . In
      addition, EPI significantly shortened action potential duration prolonged by As2
      O3 . Our data suggest that EPI rescues As2 O3 -induced HERG channel deficiency
      through upregulating SP1 expression.

PMID- 28768060
TI  - Factors associated with shared decision making among primary care physicians:
      Findings from a multicentre cross-sectional study.
AB  - BACKGROUND: Despite growing recognition that shared decision making (SDM) is
      central for patient-centred primary care, adoption by physicians remains limited
      in routine practice. OBJECTIVE: To examine the characteristics of physicians,
      patients and consultations associated with primary care physicians' SDM
      behaviours during routine care. METHODS: A multicentre cross-sectional survey
      study was conducted with 114 unique patient-physician dyads recruited from 17
      primary care clinics in Quebec and Ontario, Canada. Physicians' SDM behaviours
      were assessed with the 12-item OPTION scale scored by third observers using audio
      recordings of consultations. Independent variables included 21 physician, patient
      and consultation characteristics. We assessed factors associated with OPTION
      scores using multivariate linear regression models. RESULTS: On the OPTION scale,
      where higher scores indicated greater SDM behaviours, physicians earned an
      overall mean score of 25.7+/-9.8 of 100. In the final adjusted regression model,
      higher OPTION scores were associated with physicians' social participation
      (involvement in one committee beta=5.75, P=.04; involvement in two or more
      committees beta=7.74, P=.01), patients' status as employed (beta=6.48, P=.02),
      clinically significant decisional conflict in patients (beta=7.15, P=.002) and a
      longer duration of consultations (beta=0.23, P=.002). CONCLUSION: Physicians'
      social participation, patients' employment status and decisional conflict and the
      duration of consultations were associated with primary care physicians' SDM
      behaviours in routine care. These factors should be considered when designing
      strategies to implement SDM and promote more patient-centred care in primary
      care.

PMID- 28768061
TI  - Why and how are we living longer?
AB  - NEW FINDINGS: What is the topic of this review? The reasons for the continuing
      increase in human life expectancy are examined in the light of progress in
      understanding the physiological basis of ageing. Prospects for further extending
      the health span - the period free of age-related disability and disease - are
      critically assessed. What advances does it highlight? No active programming
      directly causes ageing, which instead results as a side effect of how evolution
      optimises the physiological allocation of resources between growth, reproduction
      and maintenance. Under pressure of natural selection, there was insufficient
      priority in maintaining the body well enough that it could endure without
      progressive accumulation of multiple kinds of molecular and cellular damage.
      Understanding human ageing is a major challenge for the physiological sciences.
      It is made all the more urgent by the survival of inreasing numbers of people to
      advanced old age and by a shift in the underlying causes of the continuing
      increase in life expectancy. The previous increase was caused almost entirely by
      the prevention of deaths in the early and middle years of life; a process that
      has seen such success that in developed countries there remains little scope for
      significant further increase from this cause. The more recent increase is driven
      by something new. We are reaching old age in generally better health, and it is
      the death rates at advanced ages that are now falling fast. At the same time,
      biology has established that there is almost certainly no fixed programme for
      ageing, which is caused instead by the lifelong accumulation of damage. It is
      becoming evident that the ageing process is much more malleable than we used to
      think. We need urgently to establish the factors that govern this malleability
      and to identify the interactions between, on the one hand, intrinsic biological
      processes that drive the many chronic diseases and disabilities for which age is
      by far the largest risk factor and, on the other hand, the social and lifestyle
      factors that influence our individual trajectories of health in old age. Ageing
      is no longer as mysterious and intractable a process as used to be thought,
      offering new opportunities for contributions from other branches of the
      physiological sciences.

PMID- 28768062
TI  - Selforganization of modular activity of grid cells.
AB  - A unique topographical representation of space is found in the concerted activity
      of grid cells in the rodent medial entorhinal cortex. Many among the principal
      cells in this region exhibit a hexagonal firing pattern, in which each cell
      expresses its own set of place fields (spatial phases) at the vertices of a
      triangular grid, the spacing and orientation of which are typically shared with
      neighboring cells. Grid spacing, in particular, has been found to increase along
      the dorso-ventral axis of the entorhinal cortex but in discrete steps, that is,
      with a modular structure. In this study, we show that such a modular activity may
      result from the self-organization of interacting units, which individually would
      not show discrete but rather continuously varying grid spacing. Within our
      "adaptation" network model, the effect of a continuously varying time constant,
      which determines grid spacing in the isolated cell model, is modulated by
      recurrent collateral connections, which tend to produce a few subnetworks, akin
      to magnetic domains, each with its own grid spacing. In agreement with
      experimental evidence, the modular structure is tightly defined by grid spacing,
      but also involves grid orientation and distortion, due to interactions across
      modules. Thus, our study sheds light onto a possible mechanism, other than simply
      assuming separate networks a priori, underlying the formation of modular grid
      representations.

PMID- 28768063
TI  - Photochemical Dual-Catalytic Synthesis of Alkynyl Sulfides.
AB  - A photochemical dual-catalytic cross-coupling to form alkynyl sulfides via C(sp)
      S bond formation is described. The cross-coupling of thiols and bromoalkynes is
      promoted by a soluble organic carbazole-based photocatalyst using continuous flow
      techniques. Synthesis of alkynyl sulfides bearing a wide range of electronically
      and sterically diverse aromatic alkynes and thiols can be achieved in good to
      excellent yields (50-96 %). The simple continuous flow setup also allows for
      short reaction times (30 min) and high reproducibility on gram scale. In
      addition, we report the first application of photoredox/nickel dual catalysis
      towards macrocyclization, as well as the first example of the incorporation of an
      alkynyl sulfide functional group into a macrocyclic scaffold.

PMID- 28768064
TI  - Electrostatic balance between global repulsion and local attraction in reentrant
      polymerization of actin.
AB  - Actin polymerization depends on the salt concentration, exhibiting a reentrant
      behavior: the polymerization is promoted by increasing KCl concentration up to
      100 mM, and then depressed by further increase above 100 mM. We here investigated
      the physical mechanism of this reentrant behavior by calculating the
      polymerization energy, defined by the electrostatic energy change upon binding of
      an actin subunit to a filament, using an implicit solvent model based on the
      Poisson-Boltzmann (PB) equation. We found that the polymerization energy as a
      function of the salt concentration shows a non-monotonic reentrant-like behavior,
      with the minimum at about 100 mM (1:1 salt). By separately examining the salt
      concentration effect on the global electrostatic repulsion between the like
      charged subunits and that on the local electrostatic attraction between the inter
      subunit ionic-bond-forming residues in the filament, we clarified that the
      reentrant behavior is caused by the change in the balance between the two
      opposing electrostatic interactions. Our study showed that the non-specific
      nature of counterions, as described in the mean-field theory, plays an important
      role in the actin polymerization. We also discussed the endothermic nature of the
      actin polymerization and mentioned the effect of ATP hydrolysis on the G-F
      transformation, indicating that the electrostatic interaction is widely and
      intricately involved in the actin dynamics.

PMID- 28768065
TI  - Multiple influences on participating in physical activity in older age:
      Developing a social ecological approach.
AB  - BACKGROUND: Evidence of the benefits of engaging in physical activity (PA) is
      strong, yet the number of older adults meeting the recommended 150 min/wk is low.
      Policy to increase uptake and adherence has focussed on the health benefits of
      PA, but may not be the most successful approach. OBJECTIVE: This qualitative
      study sought to ask older adults what the components of a successful intervention
      to promote PA would be, by asking active older adults what motivated them to be
      active and asking inactive older adults what might encourage them to change.
      DESIGN, SETTING AND PARTICIPANTS: Focus groups and semi-structured interviews
      were held with 60 community-dwelling older adults, aged 50-87 years. Framework
      analysis was used to analyse the data, and themes congruent with a social
      ecological model of behaviour change were developed. FINDINGS: Five themes
      emerged that influenced PA engagement at multiple levels: individual;
      interpersonal; perceived environment; community or organizational; and policy. PA
      engagement was determined by attitude or health status for some participants, but
      for the majority, PA being enjoyable, sociable, affordable, accessible, flexible
      and seasonal were more important than the health benefits. DISCUSSION AND
      CONCLUSIONS: A social ecological model is presented, highlighting the fact that
      both motivated and unmotivated older adults need to have a range of appropriately
      labelled, appealing and accessible activities to choose from when thinking about
      engaging in PA. Policymakers and practitioners need to ensure that their offers
      of activity sessions are easy to access and easy to remain involved in.

PMID- 28768066
TI  - Chemical Pulping Advantages of Zip-lignin Hybrid Poplar.
AB  - Hybrid poplar genetically engineered to possess chemically labile ester linkages
      in its lignin backbone (zip-lignin hybrid poplar) was examined to determine if
      the strategic lignin modifications would enhance chemical pulping efficiencies.
      Kraft pulping of zip-lignin and wild-type hybrid poplar was performed in lab
      scale reactors under conditions of varying severity by altering time, temperature
      and chemical charge. The resulting pulps were analyzed for yield, residual lignin
      content, and cellulose DP (degree of polymerization), as well as changes in
      carbohydrates and lignin structure. Statistical models of pulping were created,
      and the pulp bleaching and physical properties evaluated. Under identical cooking
      conditions, compared to wild-type, the zip-lignin hybrid poplar showed extended
      delignification, confirming the zip-lignin effect. Additionally, yield and
      carbohydrate content of the ensuing pulps were slightly elevated, as was the
      cellulose DP for zip-lignin poplar pulp, although differences in residual lignin
      between zip-lignin and wild-type poplar were not detected. Statistical prediction
      models facilitated comparisons between pulping conditions that resulted in
      identical delignification, with the zip-lignin poplar needing milder cooking
      conditions and resulting in higher pulp yield (up to 1.41 % gain). Bleaching and
      physical properties were subsequently equivalent between the samples with slight
      chemical savings realized in the zip-lignin samples due to the enhanced
      delignification.

PMID- 28768067
TI  - "This illness diminishes me. What it does is like theft": A qualitative meta
      synthesis of people's experiences of living with asthma.
AB  - BACKGROUND: What matters to people in their everyday experiences of living with
      asthma is influenced by a diverse range of personal, social, medical and
      environmental factors. Previous reviews of the asthma literature have largely
      focused on medical aspects of asthma or specific population groups with
      particular needs. OBJECTIVE: To identify, describe and synthesize from the
      available qualitative literature the views and experiences of adults living with
      asthma. METHOD: We systematically searched for qualitative studies reporting on
      the personal experience of living with asthma. A meta-synthesis approach was used
      to analyse and interpret the data. Key themes relating to personal perspectives
      on asthma were identified and grouped into overarching concepts. RESULTS: We
      identified 26 studies. There was a paucity of literature on the physical burden
      of asthma symptoms and the role of social support. Our synthesis generated a
      central concept of the "work" associated with living with asthma: work was of a
      personal nature, and at times an intensely emotional experience. Individuals
      tailored their behaviour in response to demands of the physical and social
      environment, including interactions with health-care professionals. CONCLUSION:
      This is the first systematic review of the qualitative literature reporting on
      people's own perspectives of living with asthma. Our findings draw attention to
      the nuances and sensitivities surrounding patient experiences of self-management.
      Medical care is a central plank of managing chronic conditions, but our health
      care systems are now expected to deliver patient-centred care. Considering the
      broader aspects of asthma management, beyond that of symptoms and treatment, will
      help to facilitate comprehensive care.

PMID- 28768068
TI  - Executive summary: The Brain Injury and Mechanism of Action of Hyperbaric Oxygen
      for Persistent Post-Concussive Symptoms after Mild Traumatic Brain Injury (mTBI)
      (BIMA) Study.
AB  - The Brain Injury and Mechanism of Action of Hyperbaric Oxygen for Persistent Post
      Concussive Symptoms after Mild Traumatic Brain Injury (mTBI) (BIMA) study,
      sponsored by the Department of Defense and held under an investigational new drug
      application by the Office of the Army Surgeon General, is one of the largest and
      most complex clinical trials of hyperbaric oxygen (HBO2) for post-concussive
      symptoms (PCS) in U.S. military service members.

PMID- 28768069
TI  - Hyperbaric oxygen for mild traumatic brain injury: Design and baseline summary.
AB  - : The Brain Injury and Mechanisms of Action of Hyperbaric Oxygen for Persistent
      Post-Concussive Symptoms after Mild Traumatic Brain Injury (mTBI) (BIMA) study,
      sponsored by the Department of Defense, is a randomized double-blind, sham
      controlled clinical trial that has a longer duration of follow-up and more
      comprehensive assessment battery compared to recent HBO2 studies. BIMA randomized
      71 participants from September 2012 to May 2014. Primary results are expected in
      2017. Randomized military personnel received hyperbaric oxygen (HBO2) at 1.5
      atmospheres absolute (ATA) or sham chamber sessions at 1.2 ATA, air, for 60
      minutes daily for 40 sessions. Outcomes include neuropsychological, neuroimaging,
      neurological, vestibular, autonomic function, electroencephalography, and visual
      systems evaluated at baseline, immediately following intervention at 13 weeks and
      six months with self-report symptom and quality of life questionnaires at 12
      months, 24 months and 36 months. Characteristics include: median age 33 years
      (range 21-53); 99% male; 82% Caucasian; 49% diagnosed post-traumatic stress
      disorder; 28% with most recent injury three months to one year prior to
      enrollment; 32% blast injuries; and 73% multiple injuries. This manuscript
      describes the study design, outcome assessment battery, and baseline
      characteristics. Independent of a therapeutic role of HBO2, results of BIMA will
      aid understanding of mTBI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01611194; https://clinicaltrials.gov/show/NCT01611194.

PMID- 28768070
TI  - Baseline neurological evaluations in a hyperbaric trial of post-concussive
      syndrome.
AB  - : Standard neurologic examinations may not detect abnormalities in U.S. military
      service members with persistent post-concussive symptoms following mild traumatic
      brain injury. The Brain Injury and Mechanisms of Action of Hyperbaric Oxygen for
      Persistent Post-Concussive Symptoms after Mild Traumatic Brain Injury Study
      (BIMA) enrolled 71 participants September 2012-May 2014. Participants received:
      comprehensive neurological and oculomotor exam; balance testing (Berg Balance
      Scale-BBS; Romberg Test-RT, Sharpened Romberg Test-SRT); olfactory function
      (Brief Smell Identification Test-BSIT). Two trained neurologists conducted the
      examinations at a central facility in Colorado Springs. Median age was 32 years
      (range 21-53), 99% male, 82% Caucasian, 49% PTSD, 28% most recent qualifying
      injury three months to one year prior to enrollment, 32% blast injuries only, and
      73% multiple injuries. Some participants presented with abnormal facial sensation
      (15%), abnormal tandem gait (13%), and tremor (11%). 54% had abnormal near point
      of convergence (abnormal range 13-80 cm). 86% scored >= 55 on the BBS, with no
      participant scoring ? 50. 49% scored ? 30 seconds on the best trial of the SRT.
      RT was abnormal in 10%. 15% of participants scored <= 9 (out of 12) on BSIT,
      about twice what is expected in a normal population. The neurological examination
      found abnormalities across a range of testing, with convergence insufficiency and
      SRT having the most sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT01611194; https://clinicaltrials.gov/show/NCT01611194.

PMID- 28768072
TI  - Linear analysis of heart rate variability in post-concussive syndrome.
AB  - : Heart rate variability (HRV) represents measurable output of coordinated
      structural and functional systems within the body and brain. Both mild traumatic
      brain injury (mTBI) and HRV are modulated by changes in autonomic nervous system
      function. We present baseline HRV results from an ongoing mTBI clinical trial.
      HRV was assessed via 24-hour ambulatory electrocardiography; recordings were
      segmented by physiological state (sleep, wakefulness, exercise, standing still).
      Time, frequency, and spatial domain measures were summarized and compared with
      symptoms, sleep quality, and neurological examination. Median low frequency/high
      frequency (LF/HF) ratio exceeded 1.0 across segments, indicating prevalence of
      sympathetic modulation. Abnormal Sharpened Romberg Test was associated with 29%
      LF/HF decrease (95% CI [2.1, 47.7], p=0.04); pathological nystagmus associated
      with decreased standard deviation of electrocardiogram R-R interval (SDNN) index
      (25% decrease, 95% CI [0.8, 43.4], p=0.04). Increased sympathetic modulation was
      associated with increased anger scores (19% LF/HF increase with 5-point State
      Trait Anger Expression Inventory-2 trait anger increase (95% CI [1.2, 39.1],
      p=0.04)). A 13% HF increase (95% CI [2.1, 25.7], p=0.02) was observed with
      increased Pittsburgh Sleep Quality Index scores. These results support autonomic
      nervous system dysfunction in service members after mTBI. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01611194;
      https://clinicaltrials.gov/show/NCT01611194.

PMID- 28768071
TI  - Baseline EEG abnormalities in mild traumatic brain injury from the BIMA study.
AB  - : The Brain Injury and Mechanisms of Action of HBO2 for Persistent Post
      Concussive Symptoms after Mild Traumatic Brain Injury (BIMA), sponsored by the
      Department of Defense, is a randomized, double-blind, sham-controlled trial of
      hyperbaric oxygen (HBO2) in service members with persistent post-concussive
      symptoms following mild TBI, undergoing comprehensive assessments. The clinical
      EEG was assessed by neurologists for slow wave activity, ictal/interictal
      epileptiform abnormalities, and background periodic discharges. There is scant
      literature about EEG findings in this population, so we report baseline clinical
      EEG results and explore associations with other evaluations, including
      demographics, medication, neurological assessments, and clinical MRI outcomes.
      Seventy-one participants were enrolled: median age 32 years, 99% male, 49%
      comorbid PTSD, 28% with mTBI in the previous year, 32% blast injuries only, and
      73% multiple injuries. All participants reported medication use (mean medications
      = 8, SD = 5). Slowing was present in 39%: generalized 37%, localized 8%, both 6%.
      No other abnormalities were identified. Slowing was not significantly associated
      with demographics, medication or neurological evaluation. Participants without
      EEG abnormalities paradoxically had significantly higher number of white matter
      hyperintensities as identified on MRI (p = 0.003). EEG slowing is present in more
      than one-third of participants in this study without evidence of associations
      with demographics, medications or neurological findings. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01611194;
      https://clinicaltrials.gov/show/NCT01611194.

PMID- 28768073
TI  - Sleep assessments for a mild traumatic brain injury trial in a military
      population.
AB  - Baseline sleep characteristics were explored for 71 U.S. military service members
      with mild traumatic brain injury (mTBI) enrolled in a post-concussive syndrome
      clinical trial. The Pittsburgh Sleep Quality Index (PSQI), sleep diary, several
      disorder-specific questionnaires, actigraphy and polysomnographic nap were
      collected. Almost all (97%) reported ongoing sleep problems. The mean global PSQI
      score was 13.5 (SD=3.8) and 87% met insomnia criteria. Sleep maintenance
      efficiency was 79.1% for PSQI, 82.7% for sleep diary and 90.5% for actigraphy;
      total sleep time was 288, 302 and 400 minutes, respectively. There was no
      correlation between actigraphy and subjective questionnaires. Overall, 70% met
      hypersomnia conditions, 70% were at high risk for obstructive sleep apnea (OSA),
      32% were symptomatic for restless legs syndrome, and 6% reported cataplexy.
      Nearly half (44%) reported coexisting insomnia, hypersomnia and high OSA risk.
      Participants with post-traumatic stress disorder (PTSD) had higher PSQI scores
      and increased OSA risk. Older participants and those with higher aggression,
      anxiety or depression also had increased OSA risk. The results confirm poor sleep
      quality in mTBI with insomnia, hypersomnia, and OSA risk higher than previously
      reported, and imply sleep disorders in mTBI may be underdiagnosed or exacerbated
      by comorbid PTSD.

PMID- 28768075
TI  - Neuropsychological assessments in a hyperbaric trial of post-concussive symptoms.
AB  - : Results of studies addressing the effect of mild traumatic brain injury (mTBI)
      and post-traumatic stress disorder (PTSD) on symptoms and neuropsychological
      assessments are mixed regarding cognitive deficits in these populations.
      Neuropsychological assessments were compared between U.S. military service
      members with mTBI only (n=36) vs. those with mTBI/ PTSD (n=35) from a randomized
      interventional study of mTBI participants with persistent post-concussive
      symptoms (PCS). The mTBI group endorsed worse symptoms than published norms on
      PCS, PTSD and pain scales (?50% abnormal on Neurobehavioral Symptom Inventory
      (NSI), PTSD Checklist-Civilian, McGill Pain Questionnaire-Short Form) and some
      quality of life domains. Worse symptom reporting was found in the mTBI/ PTSD
      group compared to mTBI (e.g., mean NSI total score in mTBI 27.5 (SD=12.7), mTBI/
      PTSD 39.9 (SD=13.6), p?0.001). The mTBI/PTSD group performed worse than mTBI on
      the Weschler Adult Intelligence Scale digit span (mean difference -1.5, 95% CI[
      2.9,-0.1], p=0.04) and symbol search (mean difference -1.5, 95% CI[-2.7,-0.2],
      p=0.03) and Grooved Pegboard (dominant hand mean difference -7.0, 95% CI[-11.5,
      2.4], p=0.003; non-dominant mean difference -9.8, 95% CI[-14.9,-4.7], p?0.001).
      Differences were detected in ANAM simple reaction time (p=0.04) and mathematical
      processing (p=0.03) but not verbal fluency or visuospatial memory assessments.
      Results indicate increased symptom severity and some cognitive deficits in mTBI/
      PTSD compared to mTBI alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01611194; https://clinicaltrials.gov/show/NCT01611194.

PMID- 28768076
TI  - Hyperbaric oxygen for persistent post-concussive symptoms: long-term follow-up.
AB  - We report results of an observational cohort study investigating long-term follow
      up in participants from two completed United States military trials of hyperbaric
      oxygen (HBO2) for persistent post-concussive symptoms (PCS), as well as
      challenges in recruitment and retention in active-duty military personnel. After
      informed consent, participants completed an electronic survey assessing PCS, post
      traumatic stress disorder (PTSD), anxiety, depression and quality of life. Of 132
      HBO2 study participants, 40 (30%) completed the survey (42 could not be
      contacted; 50 were lost to follow-up or declined). All were male, age 28.1 +/-6.6
      years (mean +/-1SD). Time to follow-up was 39.2 +/-6.1 months. At follow-up,
      participants reported continued symptoms of PTSD, depression, anxiety and reduced
      quality of life. Among DARPA/VCU study participants, total PCS scores worsened in
      the 1.5 atmospheres absolute (ATA) equivalent HBO2 group (mean change 7.4 +/
      15.8) and improved in the sham (-8.0 +/-7.7) and 2.0 atmospheres absolute
      equivalent HBO2 groups (-3.3 +/-7.4). Individual changes varied widely, range -23
      to +28 points. In participants from the HOPPS study, total PCS scores worsened in
      all groups: local care (10.5 +/-8.7), sham (7.9 +/-11.9) and 1.5 ATA HBO2 (1.0 +/
      19.4). In this limited, cross-sectional sample, PCS and PTSD symptoms did not
      appear to improve over time by descriptive analyses. Low participation rates and
      potential response bias limit our ability to perform statistical hypothesis
      testing and to draw conclusions from these data. Future studies should
      prospectively plan longitudinal follow-up and regular engagement with
      participants to minimize attrition.

PMID- 28768077
TI  - Review of recent non-hyperbaric oxygen interventions for mild traumatic brain
      injury.
AB  - Traumatic brain injury (TBI) affects 3.2 to 5.3 million persons in the United
      States (U.S.), and the impact in the U.S. military is proportionally higher.
      Consensus is lacking regarding an accepted outcome to measure the effectiveness
      of interventions to improve the symptoms associated with TBI, and no standard-of
      care treatment exists for mild TBI (mTBI). A recent literature review evaluated
      hyperbaric oxygen therapy (HBO2) interventions, and findings were mixed. We
      conducted a systematic review of non-HBO2 mTBI interventional trials published in
      2005-2015 in military and civilian populations. A total of 154 abstracts, seven
      randomized controlled trials (RCTs) and five pilot studies were reviewed. RCTs
      were evaluated using Consolidated Standards of Reporting Trials criteria. Results
      indicated that studies published within the period of review were small pilot
      studies for rehabilitation therapy and motion capture or virtual reality gaming
      interventions. Neuropsychological assessments were commonly specified outcomes,
      and most studies included a combination of symptom and neuropsychological
      assessments. Findings indicated a lack of large-scale, well-controlled trials to
      address the symptoms and sequelae of this condition, but results of small
      exploratory studies show evidence of potentially promising interventions.

PMID- 28768078
TI  - Hyperbaric medicine today: an historically noble discipline challenged by loss of
      critical access and overutilization -- an introduction to invited commentary.

PMID- 28768079
TI  - Hyperbaric medicine today: an historically noble discipline challenged by loss of
      critical access and overutilization - invited commentary.
AB  - As the title implies, much appears amiss with hyperbaric medicine. Long
      recognized for its life-saving, CNS-sparing,infection-fighting and tissue-salving
      attributes, its current application has been rightly called into question by a
      broad cross-section of health care delivery system stakeholders [1, 2, 3, 4, 5].
      This paper will examine what lies behind the stunning loss of availability for a
      majority of the Federal Drug Administration-approved uses, arguably those for
      which patients have the most to gain. It will address overutilization in the
      context of an erosion of practice standards and widespread manipulation of the
      reimbursement process. It will make suggestions aimed at restoring its broader
      availability across the full extent of FDA-approved uses. Finally, it offers
      guidance to ensure that HBO2 therapy is employed only when medically necessary by
      adoption of the drug administration "rights" principle, namely the right
      indication for the right patient at the right time and only for the right amount
      of time.

PMID- 28768080
TI  - Garage carbon monoxide levels from sources commonly used in intentional
      poisoning.
AB  - BACKGROUND: The incidence of intentional carbon monoxide (CO) poisoning is
      believed to have declined due to strict federal CO emissions standards for motor
      vehicles and the uniform application of catalytic converters (CC). We sought to
      compare ambient CO levels produced by automobiles with and without catalytic
      converters in a residential garage, as well as from other CO sources commonly
      used for intentional poisoning. METHODS: CO levels were measured inside a
      freestanding 73 m3 one-car garage. CO sources included a 1971 automobile without
      CC, 2003 automobile with CC, charcoal grill, electrical generator, lawn mower and
      leaf blower. RESULTS: After 20 minutes of operation, the CO level in the garage
      was 253 PPM for the car without a catalytic converter and 30 PPM for the car
      equipped withone. CO levels after operating or burning the other sources were:
      charcoal 200 PPM; generator >999 PPM; lawn mower 198 PPM; and leaf blower 580
      PPM. CONCLUSIONS: While emissions controls on automobiles have reduced
      intentional CO poisonings, alternate sources may produce CO at levels of the same
      magnitude as vehicles manufactured prior to the use of catalytic converters.
      Those involved in the care of potentially suicidal individuals should be aware of
      this.

PMID- 28768081
TI  - Evaluation of the Carefusion Alaris PC infusion pump for hyperbaric oxygen
      therapy conditions: Technical report.
AB  - We present a standardized test methodology and results for our evaluation of the
      Carefusion Alaris PC infusion pump, comprising the model 8015 PC Unit and the
      model 8100 Large Volume Pump (LVP) module. The evaluation consisted of basic
      suitability testing, internal component inspection, surface temperature
      measurement of selected internal components, and critical performance testing
      (infusion rate accuracy and occlusion alarm pressure) during conditions of
      typical hyperbaric oxygen (HBO2) treatment in our facility's class A multiplace
      chamber. We have found that the pumps pose no enhanced risk as an ignition
      source, and that the pumps operate within manufacturer's specifications for flow
      rate and occlusion alarms at all stages of HBO2 treatments, up to 4.0 ATA and
      pressurization and depressurization rates up to 180 kPa/minute. The pumps do not
      require purging with air or nitrogen and can be used unmodified, subject to the
      following conditions: pumps are undamaged, clean, fully charged, and absent from
      alcohol cleaning residue; pumps are powered from the internal NiMH battery only;
      maximum pressure exposure 4.0 ATA; maximum pressurization and depressurization
      rate of 180 kPa/minute; LVP modules locked in place with retaining screws.

PMID- 28768082
TI  - Test results for the evaluation of a glucometer for use under hyperbaric
      conditions: Technical report.
AB  - This study aimed to evaluate a recently developed equipment test method by
      assessing the safe and accurate functioning of the Abbott Optium FreeStyle H
      portable blood glucose monitor for use in the Alfred Hospital's hyperbaric
      chamber. The results of this study indicate that the test method can be used
      successfully to evaluate instruments and/or devices for use in the hyperbaric
      environment. The evaluation initially found that this particular glucose monitor
      contained a lithium battery which can be hazardous when used in the hyperbaric
      environment. However, upon further inspection it was determined the battery posed
      minimal risk for fire and explosion due to its small capacity and design
      application. The results indicate that the Abbott Optium FreeStyle H blood
      glucose monitor operated normally when used in the hyperbaric chamber. This
      glucometer was found to perform within the calibration specification requirements
      for accuracy at all stages of a typical hyperbaric treatment and as such the
      Abbott Optium FreeStyle H blood glucose monitor was deemed safe for use in the
      hyperbaric chamber at the Alfred Hospital.

PMID- 28768084
TI  - Changes in angiotensin II and angiotensin-converting enzyme of different tissues
      after prolonged hyperoxia exposure.
AB  - Current study findings concerning changes in the renin-angiotensin system (RAS)
      in cases of hyperoxic acute lung injury (HALI) have shown conflicting results.
      This study aimed to detect the angiotensin II (Ang II) and angiotensin-converting
      enzyme (ACE) in a rat HALI model. Healthy male Sprague-Dawley rats were randomly
      assigned into three groups: the control group, HALI group and hyperbaric oxygen
      preconditioning (HBO2-PC) group. HALI was induced by exposure to pure oxygen at
      250 kPa for six hours. In the HBO2-PC group, rats were exposed to oxygen at 250
      kPa for 60 minutes twice daily for two consecutive days; HALI was induced at 24
      hours after the last oxygen exposure.=After HALI, the lung, spleen and liver were
      harvested for HE staining and pathological examination. At one hour and 18 hours
      after HALI, the blood, liver, lung and spleen were collected for the detection of
      Ang II and ACE contents by enzyme-linked immunosorbent assay. Pathological
      examination showed the lung was significantly damaged and characteristics of HALI
      were observed, but there were no significant pathological changes in the liver
      and spleen. After HALI, Ang II and ACE contents of different tissues increased
      progressively over time, but the HBO2-PC group showed reductions in the Ang II
      and ACE contents to a certain extent, especially at 18 hours after injury. These
      findings suggest prolonged hyperoxia exposure may activate the RAS, which may be
      associated with the pathogenesis of HALI. HBO2-PC has a limited capability to
      inhibit RAS activation.

PMID- 28768083
TI  - Oridonin protects the lung against hyperoxia-induced injury in a mouse model.
AB  - Hyperoxic acute lung injury (HALI) is caused by prolonged exposure to high oxygen
      partial pressure. This study was undertaken to investigate the protective effects
      of oridonin on HALI in a mouse model. Mice were randomly divided into three
      groups: the control group, HALI group and oridonin (ORI) group. HALI was induced
      by exposing mice to pure oxygen at 2.5 atmospheres absolute (ATA) for six hours
      in the HALI and ORI groups. In the ORI group, mice were intraperitoneally
      injected with ORI at 10 mg/kg twice daily after hyperoxic exposure. Animals were
      sacrificed 24 hours after the hyperoxia exposure, followed by bronchoalveolar
      lavage fluid (BALF). Lungs were then collected. Each lung was processed for HE
      staining and detection of wet-to-dry weight ratio. The lactate dehydrogenase
      (LDH) activity and protein content of BALF were determined, and the contents of
      malonaldehyde (MDA), glutathione (GSH), tumor necrosis factor alpha (TNF-?) and
      interleukin-10 (IL-10) in the lung were measured. Our results showed prolonged
      exposure to hyperoxia significantly damaged the lung, caused lung edema,
      increased MDA and TNF-?, and reduced GSH and IL-10 in the lung. However, post
      exposure treatment with oridonin was able to improve lung pathology, attenuate
      lung edema, reduce MDA and TNF-?, and increase GSH and IL-10 in the lung. These
      findings suggest that oridonin can protect the lung against hyperoxia-induced
      injury in mice.

PMID- 28768085
TI  - Scuba in older-aged divers.
AB  - As the population gets older, coupled with increased awareness of good health
      practices and the recognition that fitness contributes to participation in
      activities generally appropriate for younger individuals, decisions need to be
      made about what are appropriate activities for the older-aged scuba (self
      contained underwater breathing apparatus) diver. It is essential to appreciate
      the distinction between chronological and physiological age. Three factors,
      namely fitness, comorbidities, and mobility and strength are fundamental when
      making decisions about participation in activities in general as well as in scuba
      diving for older adults. There is almost always a time to call it quits for
      everything.

PMID- 28768086
TI  - Relationship between clinical and radiologic findings of spinal cord injury in
      decompression sickness.
AB  - BACKGROUND: Decompression sickness may involve the central nervous system. The
      most common site is spinal cord. This study was conducted to determine the
      relationship between magnetic resonance(MR) imaging findings of spinal damage.
      METHODS: We conducted a retrospective review of 12 patients (male=10, female=2)
      who presented with spinal cord symptoms. We investigated their clinical features,
      neurological findings and radiologic findings. RESULTS: The depth and bottom time
      of the dive were 34.5 meters (range 22-56) and 22.7 minutes (range 10-55)
      respectively. Most divers ascended within appropriate time frame as shown by the
      decompression tables. The most frequent initial symptoms were lower limb weakness
      (n=12), followed by sensory disturbances (n=10) and bladder dysfuction (n=5). The
      chief radiologic abnormalities were continuous (n=3), or non-continuous (n=5)
      high-signal intensity on T2-weighted images at posterior paramedian portion of
      the spinal cord, mainly thoracic level. There were no abnormal findings in the
      remaining four (4) patients, and they showed good prognosis. All patients were
      treated with hyperbaric oxygen therapy and some received high-dose dexamethasone.
      On discharge, five (5) patients had made a full recovery, seven (7) had some
      residual neurological sequelae, and all patients except one (1) regained normal
      bladder function. CONCLUSIONS: Spinal cord decompression sickness is a
      neurological emergency. Early recognition and treatment may minimize neurological
      damage. Initial normal finding in MR imaging was a good predictor for prognosis
      in spinal decompression sickness.

PMID- 28768087
TI  - Adjunctive hyperbaric oxygen treatment for idiopathic sudden sensorineural
      hearing loss.
AB  - INTRODUCTION: This study aims to evaluate the hearing gain efficacy from
      adjunctive hyperbaric oxygen (HBO2) treatment in patients with idiopathic sudden
      sensorineural hearing loss (ISSHL). MATERIALS AND METHODS: A retrospective
      analysis of chart reviews was performed on patients with ISSHL between January
      2013 through December 2015. All patients were referred to us from our ENT
      Department for adjunctive hyperbaric oxygen treatment. The results were assessed
      through pure-tone audiometry (PTA) data change (hearing gain), both before and
      after HBO2) treatment. Age, gender, affected ear side, HBO2) treatment sessions,
      both before and after HBO2 treatment PTA were all recorded. RESULTS: Ninety-three
      (93) patients with ISSHL were included in the study. The average hearing gain in
      this study was 17.9 dB (p=0.001), where a total of 46 (49.46%) patients showed an
      improvement (hearing gain>=dB) in response to HBO2 treatment (p=0.002). Patients
      with the poorest initial severity of hearing loss who displayed a greater degree
      of hearing improvement after HBO2 treatment were male and in the 40- to 59-year
      old age group. CONCLUSION: This study found that adjunctive hyperbaric oxygen
      treatment was efficacious for patients with idiopathic sudden sensorineural
      hearing loss. The total average hearing gain was recorded to be 17.9 dB.

PMID- 28768088
TI  - Non-dysbaric arterial gas embolism associated with chronic necrotizing pneumonia,
      bullae and coughing: a case report.
AB  - Arterial gas embolism (AGE) can be clinically devastating, and is most often
      associated with exposure to changes in ambient pressure, medical procedure or
      congenital malformation. Here we report a case of AGE in a 78-year-old male
      without these traditional risk factors. Rather, the patient's history included
      chronic obstructive pulmonary disease, necrotizing pneumonia, bullous disease and
      coughing. He was safely treated with hyperbaric oxygen (HBO2) therapy for AGE,
      with initial clinical improvement, but ultimately died from his underlying
      condition. Pathophysiology is discussed. This case illustrates the possibility
      that AGE can occur due to rupture of lung tissue in the absence of traditional
      risk factors. HBO2 therapy should be considered in the management of such
      patients.

PMID- 28768089
TI  - Bebe Vio: On top of the world.

PMID- 28768091
TI  - IPE, SDPE, PESD: What's in a name?

PMID- 28768090
TI  - Erratum regarding inaccurate authorship attributions noted.
AB  - For the paper 'Hyperbaric programs in the United States: Locations and
      capabilities of treating decompression sickness, arterial gas embolisms, and
      acute carbon monoxide poisoning: survey results,' authorship and affiliations in
      UHM 43-1 read as: Chin W, Jacoby L, Simon O, Talati N, Wegrzyn G, Jacoby R,
      Proano J, Sprau SE, Markovitz G, Hsu R, Joo E. Undersea Hyperb Med. 2016 Jan-Feb;
      43(1): 29-43. The corrected authorship reads as: Chin W, Jacoby L, Simon O,
      Talati N, Wegrzyn G, Jacoby R, Proano J, Sprau SE, Markovitz GH, Hsu R, Joo E.
      Undersea Hyperb Med. 2016 Jan-Feb; 43(1): 29-43.

PMID- 28768092
TI  - TBI study questioned: Dr. Gottlieb.

PMID- 28768093
TI  - TBI study questioned: Dr. Weaver response.

PMID- 28768094
TI  - TBI study questioned: Dr. Gottlieb's response to Dr. Weaver.

PMID- 28768095
TI  - Investigating the Influence of Membrane Composition on Protein-Glycolipid Binding
      Using Nanodiscs and Proxy Ligand Electrospray Ionization Mass Spectrometry.
AB  - This work describes a versatile analytical approach, which combines the proxy
      ligand electrospray ionization mass spectrometry (ESI-MS) assay and model
      membranes of defined composition, to quantify the influence of lipid bilayer
      composition on protein-glycolipid binding in vitro. To illustrate the
      implementation of the assay (experimental design and data analysis), affinities
      of the monosialoganglioside ligand GM1, incorporated into nanodiscs (NDs), for
      cholera toxin B subunit homopentamer (CTB5) were measured. A series of NDs
      containing GM1 and cholesterol were prepared using three different phospholipids
      (1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
      (POPC)), and the average GM1 and cholesterol content of each ND were determined.
      The intrinsic affinities of GM1-containing NDs prepared with the three
      phospholipids are found to be similar in magnitude, indicating that small
      differences in the fatty acid chain length and the number of unsaturated bonds do
      not significantly affect the CTB5-GM1 interaction. Moreover, the measured
      affinities are similar to the value measured for GM1 pentasaccharide, indicating
      that neither the ceramide moiety nor the surface of the phospholipid membrane
      plays a significant role in CTB5 binding. The intrinsic (per binding site)
      affinity of the CTB5-GM1 interaction was found to decrease with increasing GM1
      content of the ND, consistent with the occurrence of GM1 clustering in the
      membrane, which sterically hinders binding to CTB5. Notably, the addition of
      cholesterol to GM1-containing NDs did not have a significant effect on the
      strength of the CTB5-GM1 interaction. This result, which is at odds with the
      findings of a previous study of CTB5 binding to GM1 in vesicles, suggests that
      cholesterol does not "mask" GM1, at least not in NDs. These data, in addition to
      providing new insights into the influence of membrane composition on CTB5-GM1
      binding, demonstrate the potential of the proxy ligand ESI-MS approach for
      comprehensive and quantitative studies of lectin interactions with glycolipids in
      native-like, membrane environments.

PMID- 28768097
TI  - The Fate of Contaminants and Stable Pb Isotopes in a Changing Estuarine
      Environment: 20 Years On.
AB  - Estuarine sediments provide an important sink for contaminants discharged into
      fluvial, estuarine, and nearshore settings, and numerous authors have utilized
      this trapping function to assess historical contaminant loadings and contaminant
      breakdown/transformation processes. This Article examines the retention of
      elemental and isotopic sedimentary signatures in an industrialized estuarine
      system subject to a strongly upward sea-level trend, over a 20 year period. Two
      contrasting saltmarsh sites (at Hythe and Hamble, part of the wider Southampton
      Water estuarine system, UK) were examined, which had been previously cored and
      analyzed in the early 1990s. Much of the geochemical record of recent
      anthropogenic activity has been eroded and lost at the Hamble site. In contrast,
      radiometric, isotopic and elemental records of anthropogenic activity have been
      retained in the Hythe marsh, with 137Cs and Cu depth profiles showing retention
      of input maxima related to fallout and local industrial discharges, respectively.
      Stable Pb isotope data show a broad degree of correspondence in cores analyzed in
      1994 and 2014 when plotted against sediment (radiometric) age, indicating the
      usefulness of isotopic data in retaining information on Pb sources and in
      disentangling Pb input histories. New ultrahigh precision, double-spike mass
      spectrometry stable Pb isotope data allow clearer discrimination of historical Pb
      input phases, and highlight within-estuary mixing and supply of reworked,
      secondary contamination from erosion of anthropogenically labeled sediments
      elsewhere in the estuary.

PMID- 28768096
TI  - Predicting Organ Toxicity Using in Vitro Bioactivity Data and Chemical Structure.
AB  - Animal testing alone cannot practically evaluate the health hazard posed by tens
      of thousands of environmental chemicals. Computational approaches making use of
      high-throughput experimental data may provide more efficient means to predict
      chemical toxicity. Here, we use a supervised machine learning strategy to
      systematically investigate the relative importance of study type, machine
      learning algorithm, and type of descriptor on predicting in vivo repeat-dose
      toxicity at the organ-level. A total of 985 compounds were represented using
      chemical structural descriptors, ToxPrint chemotype descriptors, and bioactivity
      descriptors from ToxCast in vitro high-throughput screening assays. Using
      ToxRefDB, a total of 35 target organ outcomes were identified that contained at
      least 100 chemicals (50 positive and 50 negative). Supervised machine learning
      was performed using Naive Bayes, k-nearest neighbor, random forest,
      classification and regression trees, and support vector classification
      approaches. Model performance was assessed based on F1 scores using 5-fold cross
      validation with balanced bootstrap replicates. Fixed effects modeling showed the
      variance in F1 scores was explained mostly by target organ outcome, followed by
      descriptor type, machine learning algorithm, and interactions between these three
      factors. A combination of bioactivity and chemical structure or chemotype
      descriptors were the most predictive. Model performance improved with more
      chemicals (up to a maximum of 24%), and these gains were correlated (rho = 0.92)
      with the number of chemicals. Overall, the results demonstrate that a combination
      of bioactivity and chemical descriptors can accurately predict a range of target
      organ toxicity outcomes in repeat-dose studies, but specific experimental and
      methodologic improvements may increase predictivity.

PMID- 28768098
TI  - N-tert-Butyl Sulfinyl Squaramide Receptors for Anion Recognition through Assisted
      tert-Butyl C-H Hydrogen Bonding.
AB  - A series of novel N-tert-butyl sulfinyl squaramide receptors have been designed
      and synthesized. Their interactions with a range of inorganic anions were studied
      in solution by 1H NMR spectroscopy. This new type of squaramide displayed better
      anion-binding abilities over conventional diphenyl squaramides. The single
      crystal analysis and DFT calulations implied the role of the tert-butyl C-H
      protons in binding Cl-. The energies of C-H...Cl- interactions were estimated to
      be 1.4-1.6 kcal/mol in solution.

PMID- 28768100
TI  - Magnetic-Field Density-Functional Theory (BDFT): Lessons from the Adiabatic
      Connection.
AB  - We study the effects of magnetic fields in the context of magnetic field density
      functional theory (BDFT), where the energy is a functional of the electron
      density rho and the magnetic field B. We show that this approach is a worthwhile
      alternative to current-density functional theory (CDFT) and may provide a viable
      route to the study of many magnetic phenomena using density-functional theory
      (DFT). The relationship between BDFT and CDFT is developed and clarified within
      the framework of the four-way correspondence of saddle functions and their convex
      and concave parents in convex analysis. By decomposing the energy into its Kohn
      Sham components, we demonstrate that the magnetizability is mainly determined by
      those energy components that are related to the density. For existing density
      functional approximations, this implies that, for the magnetizability,
      improvements of the density will be more beneficial than introducing a magnetic
      field dependence in the correlation functional. However, once a good charge
      density is achieved, we show that high accuracy is likely only obtainable by
      including magnetic-field dependence. We demonstrate that adiabatic-connection
      (AC) curves at different field strengths resemble one another closely provided
      each curve is calculated at the equilibrium geometry of that field strength. In
      contrast, if all AC curves are calculated at the equilibrium geometry of the
      field-free system, then the curves change strongly with increasing field strength
      due to the increasing importance of static correlation. This holds also for
      density functional approximations, for which we demonstrate that the main error
      encountered in the presence of a field is already present at zero field strength,
      indicating that density-functional approximations may be applied to systems in
      strong fields, without the need to treat additional static correlation.

PMID- 28768099
TI  - A Multidimensional B-Spline Correction for Accurate Modeling Sugar Puckering in
      QM/MM Simulations.
AB  - The computational efficiency of approximate quantum mechanical methods allows
      their use for the construction of multidimensional reaction free energy profiles.
      It has recently been demonstrated that quantum models based on the neglect of
      diatomic differential overlap (NNDO) approximation have difficulty modeling
      deoxyribose and ribose sugar ring puckers and thus limit their predictive value
      in the study of RNA and DNA systems. A method has been introduced in our previous
      work to improve the description of the sugar puckering conformational landscape
      that uses a multidimensional B-spline correction map (BMAP correction) for
      systems involving intrinsically coupled torsion angles. This method greatly
      improved the adiabatic potential energy surface profiles of DNA and RNA sugar
      rings relative to high-level ab initio methods even for highly problematic NDDO
      based models. In the present work, a BMAP correction is developed, implemented,
      and tested in molecular dynamics simulations using the AM1/d-PhoT semiempirical
      Hamiltonian for biological phosphoryl transfer reactions. Results are presented
      for gas-phase adiabatic potential energy surfaces of RNA transesterification
      model reactions and condensed-phase QM/MM free energy surfaces for nonenzymatic
      and RNase A-catalyzed transesterification reactions. The results show that the
      BMAP correction is stable, efficient, and leads to improvement in both the
      potential energy and free energy profiles for the reactions studied, as compared
      with ab initio and experimental reference data. Exploration of the effect of the
      size of the quantum mechanical region indicates the best agreement with
      experimental reaction barriers occurs when the full CpA dinucleotide substrate is
      treated quantum mechanically with the sugar pucker correction.

PMID- 28768101
TI  - Dependence of Binding Free Energies between RNA Nucleobases and Protein Side
      Chains on Local Dielectric Properties.
AB  - In order to fully understand the microscopic origins of binding specificity
      between nucleic acids and proteins, it is imperative to study the dependence of
      the binding preferences between nucleobases and protein side chains on the
      properties of the environment. Here, we employ molecular dynamics simulations and
      umbrella sampling to derive the potentials of mean force and the associated
      absolute binding free energies between the four standard RNA nucleobases and the
      side chains of aspartic acid and tryptophan in water/methanol mixtures exhibiting
      a wide range of dielectric constants. In addition to their opposing character
      when it comes to hydrophobicity, aspartate and tryptophan side chains were chosen
      because they exhibit the greatest change in binding free energies with
      nucleobases between pure water and methanol environments. We exploit a strong
      linear dependence of the derived DeltaG values on the mole fraction of methanol
      to estimate the binding free energies of all possible combinations of different
      standard RNA nucleobases and side chains at multiple values of dielectric
      constants. Finally, we critically assess the recently proposed complementarity
      hypothesis concerning direct, coaligned binding between mRNAs and their cognate
      proteins in light of the present results.

PMID- 28768102
TI  - Chemical Approaches to Intervening in Ubiquitin Specific Protease 7 (USP7)
      Function for Oncology and Immune Oncology Therapies.
AB  - Ubiquitin specific protease 7 (USP7), the most widely studied among the nearly
      100 deubiquitinating enzymes, supports cancer by positively affecting tumor
      growth and negatively affecting the patient's immune response to tumors. Great
      interest exists, therefore, in developing USP7 inhibitors for clinical
      evaluation. While the proteasome inhibitor field has enjoyed clinical success,
      very few clinically appropriate effectors of deubiquitinating (protease) or
      ubiquitinating (ligase) enzymes have appeared. The ubiquitin protease/ligase
      field is moving from the initial discovery of potent, selective modulators with
      cell proof of concept and in vivo activity to the optimization of these molecules
      to impart drug-like properties or the discovery of new inhibitor scaffolds by
      improved screening or rational design. This Perspective focuses on the current
      status of USP7 inhibitors from various organizations active in developing these
      compounds for the clinic and suggests undertakings that are both achievable and
      necessary to lead to successful clinical outcomes for USP7 inhibitors in cancer
      treatment.

PMID- 28768103
TI  - Application of Spectral Accuracy to Improve the Identification of Organic
      Compounds in Environmental Analysis.
AB  - Correct identification of a chemical substance in environmental samples based
      only on accurate mass measurements can be difficult especially for molecules >300
      Da. Here is presented the application of spectral accuracy, a tool for the
      comparison of isotope patterns toward molecular formula generation, as a
      complementary technique to assist in the identification process of organic
      micropollutants and their transformation products in surface water. A set of nine
      common contaminants (five antibiotics, an herbicide, a beta-blocker, an
      antidepressant, and an antineoplastic) frequently found in surface water were
      spiked in methanol and surface water extracts at two different concentrations (80
      and 300 MUg L-1). They were then injected into three different mass analyzers
      (triple quadrupole, quadrupole-time-of-fight, and quadrupole-orbitrap) to study
      the impact of matrix composition, analyte concentration, and mass resolution on
      the correct identification of molecular formulas using spectral accuracy. High
      spectral accuracy and ranking of the correct molecular formula were in many cases
      compound-specific due principally to conditions affecting signal intensity such
      as matrix effects and concentration. However, in general, results showed that
      higher concentrations and higher resolutions favored ranking the correct formula
      in the top 10. Using spectral accuracy and mass accuracy it was possible to
      reduce the number of possible molecular formulas for organic compounds of
      relative high molecular mass (e.g., between 400 and 900 Da) to less than 10 and
      in some cases, it was possible to unambiguously assign one specific molecular
      formula to an experimental isotopic pattern. This study confirmed that spectral
      accuracy can be used as a complementary diagnostic technique to improve
      confidence levels for the identification of organic contaminants under
      environmental conditions.

PMID- 28768104
TI  - Electrostatically Assembled Magnetite Nanoparticles/Graphene Foam as a Binder
      Free Anode for Lithium Ion Battery.
AB  - Lithium ion batteries (LIBs) are promising candidates for energy storage, with
      the development of novel anode materials. We report the fabrication of Fe3O4
      nanoparticles/graphene foam via electrostatic assembly and directly utilize it as
      a binder-free anode for LIBs. Owing to the integrated effect of the well
      dispersed Fe3O4 nanoparticles and the conductive graphene foam network, such
      composite exhibited remarkable electrochemical performances. It delivered a large
      reversible specific capacity reaching to ~1198 mAh g-1 at a current density of
      100 mA g-1, a good rate capacity, and an excellent cyclic stability over 400
      cycles. This work demonstrated a facile methodology to design and construct high
      performance anode materials for LIBs.

PMID- 28768106
TI  - Development of High Capacity Enterosorbents for Aflatoxin B1 and Other Hazardous
      Chemicals.
AB  - Previously, a calcium montmorillonite clay (NovaSil) included in the diet of
      animals has been shown to bind aflatoxin B1 (AfB1) and reduce the symptoms of
      aflatoxicosis. To investigate and improve the capacity and efficacy of clay-based
      materials as aflatoxin sorbents, we developed and tested calcium and sodium
      montmorillonite clays amended with nutrients including l-carnitine and choline.
      Also, we determined the sorption of AfB1 by isothermal analysis and tested the
      ability of these amended sorbents to protect adult hydra from AfB1 toxicity. The
      results showed that exchanging montmorillonite clays with l-carnitine and choline
      inhibited swelling of the clays and increased the sorption capacity and efficacy
      of clay surfaces for AfB1. Results from dehydroxylated and heat-collapsed clays
      suggested that AfB1 was primarily adsorbed in the clay interlayer, as predicted
      from thermodynamic calculations and computational modeling. The hydra bioassay
      further indicated that the modified clays can significantly protect adult hydra
      from AfB1 with as low as 0.005% clay inclusion. This enterosorbent therapy may
      also be applied to screen hazardous chemicals such as pesticides and PAHs based
      on similar sorption mechanisms. Taken together, enterosorbent therapy could be
      delivered in nutritional supplements, foods that are vulnerable to aflatoxin
      contamination, flavored liquids and animal feeds during emergencies and outbreaks
      of acute aflatoxicosis, and as a screening model for hazardous environmental
      chemicals.

PMID- 28768105
TI  - Exhaled Breath Markers for Nonimaging and Noninvasive Measures for Detection of
      Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is the most common chronic neurological disease affecting
      young adults. MS diagnosis is based on clinical characteristics and confirmed by
      examination of the cerebrospinal fluids (CSF) or by magnetic resonance imaging
      (MRI) of the brain or spinal cord or both. However, neither of the current
      diagnostic procedures are adequate as a routine tool to determine disease state.
      Thus, diagnostic biomarkers are needed. In the current study, a novel approach
      that could meet these expectations is presented. The approach is based on
      noninvasive analysis of volatile organic compounds (VOCs) in breath. Exhaled
      breath was collected from 204 participants, 146 MS and 58 healthy control
      individuals. Analysis was performed by gas-chromatography mass-spectrometry (GC
      MS) and nanomaterial-based sensor array. Predictive models were derived from the
      sensors, using artificial neural networks (ANNs). GC-MS analysis revealed
      significant differences in VOC abundance between MS patients and controls. Sensor
      data analysis on training sets was able to discriminate in binary comparisons
      between MS patients and controls with accuracies up to 90%. Blinded sets showed
      95% positive predictive value (PPV) between MS-remission and control, 100%
      sensitivity with 100% negative predictive value (NPV) between MS not-treated (NT)
      and control, and 86% NPV between relapse and control. Possible links between VOC
      biomarkers and the MS pathogenesis were established. Preliminary results suggest
      the applicability of a new nanotechnology-based method for MS diagnostics.

PMID- 28768107
TI  - Primary Care Providers' Perspectives on Screening Older Adult Patients for Food
      Insecurity.
AB  - Food insecurity has been associated with poor health and health outcomes among
      older adults, yet food assistance resources are available and underutilized.
      Routine screening and referral for food insecurity in primary care is one avenue
      to connect food-insecure older adults with available resources. This qualitative
      study aims to better understand the beliefs of primary care providers (PCPs)
      about food security screening and referrals in a primary care setting and
      perceived barriers to implementation. PCPs (n = 16) who have older adult patients
      but do not routinely screen for food insecurity were interviewed by phone. PCPs
      recognize the importance of food security for older patients and discuss
      nutrition and food access with patients under certain circumstances. Concerns
      emerged with regard to implementing a systematic screening and referral process:
      limited time to meet with patients, a lack of resources for addressing food
      insecurity, and prioritizing food insecurity at both the health system and the
      patient levels. Despite perceived challenges, PCPs are receptive to the idea of
      systematically screening and referring patients to external resources for food
      assistance and support. Barriers could be addressed by health systems
      prioritizing food insecurity as a health concern and public and private payers
      providing reimbursement for screening.

PMID- 28768108
TI  - A cross-sectional study of chiropractic students' research readiness using the
      Academic Self-Concept Analysis Scale.
AB  - OBJECTIVE: The shift toward evidence-based health care has reoriented tertiary
      clinical education in a way that necessitates and incorporates research. This
      study assesses the inclination and suitability of chiropractic students for
      research over a 5-year educational program. METHODS: Research attributes of
      chiropractic students were assessed in this cross-sectional study using a
      validated and modified academic self-concept analysis scale. Students in first
      and final year were assessed in 4 domains: creativity, motivation, self
      regulation, and general intellectual ability. Univariable differences were
      assessed using Welch 2-sample t tests, and multivariable analysis was carried out
      with multiple linear regression models. RESULTS: The response rate was 71% (n =
      165). First- and fifth-year students scored highly on all 4 domains (80% to 96%).
      Compared to first-year students, fifth-year students rated themselves
      significantly lower in 3 of the domains: general intellectual abilities (t[126] =
      -2.01; p = 0.047), motivation (t[115] = -4.82; p < 0.001), and creativity (t[136]
      = -3.00; p = 0.003). CONCLUSION: Research suitability is high in chiropractic
      students. Both cohorts scored high in all domains despite the disparity between
      first and fifth years. First-year students outperformed fifth-year students in 3
      domains, indicating a potential decline in the inclination to do research over
      time. However, unaccounted factors, such as the Dunning-Kruger effect, life
      changes, and "burnout," may have contributed to these differences. Future studies
      should include questions about stress, fatigue, clinical orientation, and
      educational environment to inform the interpretation of findings.

PMID- 28768109
TI  - Reflections on International Certified Nursing Assistants.
AB  - The author, a former university faculty member who taught English to speakers of
      other languages and now a nursing home resident, shares her observations about
      how English language proficiency, culture, and religious differences affect her
      care. She provides examples of communication challenges that can be annoying or
      cause harm, her coping strategies, and reasons many certified nursing assistants
      might never be fully fluent in English. She explains how international certified
      nursing assistants can benefit residents because of skills developed by family
      centered care in their countries of origin. She also discusses related issues-the
      importance of being culturally competent about U.S. culture. She points out how
      religiousness not only affects residents but is a buffer for staff against the
      stress of physically and emotionally demanding low-wage work. Overall, the author
      likes receiving care from individuals from other countries, finding reward in
      comparing how her personal struggle with illness and paralysis resonates with the
      trauma of migration and how learning firsthand about varying beliefs and
      attitudes clarifies her identity and place in world history.

PMID- 28768110
TI  - First Report of Human Gastroenteritis Caused by Escherichia coli O157:NM in
      Brazil.
AB  - In September 2005, the Sanitary Surveillance Service of Rio de Janeiro (SSS/RJ),
      Brazil, investigated a case of gastroenteritis involving a 13-year-old teenager
      hospitalized because of bloody diarrhea and severe abdominal pain. Owing to the
      severity of the symptoms, an epidemiological investigation was conducted in two
      states of Brazil. Escherichia coli O157:NM was isolated from stools and from a
      tomato and cheese salad prepared at the school canteen where the teenager
      attended. This is the first report of a human case of gastroenteritis related to
      E. coli O157:NM infection in Brazil.

PMID- 28768111
TI  - Providing Pediatric Palliative Care Education Using Problem-Based Learning.
AB  - BACKGROUND: The Institute of Medicine and the American Academy of Pediatrics has
      called for improvement in education and training of pediatricians in pediatric
      palliative care (PPC). Given the shortage of PPC physicians and the immediate
      need for PPC medical education, this study reports the outcomes of a problem
      based learning (PBL) module facilitated by academic general and subspecialty
      pediatric faculty (non-PPC specialists) to third year medical students.
      Objectives/Setting: To test the effectiveness of a PPC-PBL module on third year
      medical students' and pediatric faculty's declarative knowledge, attitudes
      toward, perceived exposure, and self-assessed competency in PPC objectives.
      DESIGN: A PBL module was developed using three PPC learning objectives as a
      framework: define core concepts in palliative care; list the components of a
      total pain assessment; and describe key principles in establishing therapeutic
      relationships with patients. A PPC physician and nurse practitioner guided
      pediatric faculty on facilitating the PPC-PBL. In Part 1, students identified
      domains of palliative care for a child with refractory leukemia and self-assigned
      questions to research and present at the follow-up session. In Part 2, students
      were expected to develop a care plan demonstrating the three PPC objectives.
      MEASUREMENTS: Measures included a knowledge exam and a survey instrument to
      assess secondary outcomes. RESULTS: Students' declarative knowledge, perceived
      exposure, and self-assessed competency in all three PPC learning objectives
      improved significantly after the PPC-PBL, p = 0.002, p < 0.001, and p < 0.001,
      respectively. There were no significant differences in faculty knowledge test
      scores from baseline to follow-up, but scores were generally high (median >80%).
      Students and faculty rated palliative care education as "important or very
      important" at baseline and follow-up. CONCLUSIONS: This study suggests that key
      concepts in PPC can be taught to medical students utilizing a PBL format and
      pediatric faculty resulting in improved knowledge and self-assessed competency in
      PPC.

PMID- 28768112
TI  - The disparate histories of binocular vision and binaural hearing.
AB  - Vision and hearing are dependent on disparities of spatial patterns received by
      two eyes and on time and intensity differences to two ears. However, the
      experiences of a single world have masked attention to these disparities. While
      eyes and ears are paired, there has not been parity in the attention directed to
      their functioning. Phenomena involving binocular vision were commented upon since
      antiquity whereas those about binaural hearing are much more recent. This history
      is compared with respect to the experimental manipulations of dichoptic and
      dichotic stimuli and the instruments used to stimulate the paired organs.
      Binocular color mixing led to studies of binaural hearing and direction and
      distance in visual localization were analyzed before those for auditory
      localization. Experimental investigations began in the nineteenth century with
      the invention of instruments like the stereoscope and pseudoscope, soon to be
      followed by their binaural equivalents, the stethophone and pseudophone.

PMID- 28768113
TI  - Building a chiropractic academy of educators: A needs assessment of selected
      faculty educators.
AB  - OBJECTIVE: Professional demands have led to health-care educator specialization
      in research or patient care. The academy movement is an avenue that attempts to
      return prestige and importance to improved instruction. The authors performed a
      needs analysis of selected faculty at 3 chiropractic colleges to assess the need
      for, and willingness to participate in, an academy of educators program. METHODS:
      An expert-developed, pretested survey was deployed using SurveyMonkey. Analysis
      of variance and regression analysis were used to address 3 research questions
      related to the academy of educators program. RESULTS: The study achieved a 53%
      response rate and reflected that an overwhelming majority of chiropractic faulty
      members (89%) reported the need for an academy of educators. The study found no
      significant differences between faculty ranks, years of experience, and
      participation willingness. CONCLUSION: A structured approach, such as an academy,
      to foster professional teaching development may create positive outcomes for an
      institution. Faculty educators were willing to engage in an efficient program
      that may improve teaching methods and create opportunities for collaborative
      working relationships, which signals the potential for wide acceptance of the
      program.

PMID- 28768114
TI  - Essential literature for the chiropractic profession: Results and implementation
      challenges from a survey of international chiropractic faculty.
AB  - OBJECTIVE: Scientific literature applicable to chiropractic practice proliferates
      in quantity, quality, and source. Chiropractic is a worldwide profession and
      varies in scope between states or provinces and from country to country. It is
      logical to consider that the focus and emphasis of chiropractic education varies
      between programs as well. This original research study endeavored to determine
      "essential literature" recommended by chiropractic faculty. The purpose of this
      article is (1) to share our results and (2) to promote discussion and explore
      means for future collaboration of chiropractic faculty through a worldwide
      platform. METHODS: A 2-phase recruitment occurred initially at the institutional
      level and subsequently at the faculty level. A Web-based survey used qualitative
      data collection methods to gather bibliographic citations. Descriptive statistics
      were calculated for demographics, and citation responses were ranked per number
      of recommendations, grouped into categories, and tabulated per journal source and
      publication date. RESULTS: Forty-one chiropractic programs were contacted,
      resulting in 30 participating chiropractic programs (16 US and 14 international).
      Forty-five faculty members completed the entire survey, submitting 126 peer
      reviewed publications and 25 additional citations. Readings emphasized clinical
      management of spine pain, the science of spinal manipulation, effectiveness of
      manual therapies, teaching of chiropractic techniques, outcomes assessments, and
      professional issues. CONCLUSION: A systematic approach to surveying educators in
      international chiropractic institutions was accomplished. The results of the
      survey provide a list of essential literature for the chiropractic profession. We
      recommend establishing a chiropractic faculty registry for improved communication
      and collaboration.

PMID- 28768115
TI  - Changes in adjustment force, speed, and direction factors in chiropractic
      students after 10 weeks undergoing standard technique training.
AB  - OBJECTIVE: To assess the force profiles of high-velocity low-amplitude thrusts
      delivered to a mannequin on a force platform by novice students given only verbal
      instructions. METHODS: Student volunteers untrained in adjusting delivered a
      series of adjustments to a mannequin on a force platform. Participants performed
      3 light, 3 normal, and 3 heavy thrusts on 5 listings specifying contact point,
      hand, and direction. Force profiles were analyzed for speed and amplitude,
      consistency, and force discrimination. Two recording sessions occurred 10 weeks
      apart. RESULTS: Sixteen participants (11 females, 5 male) completed the study.
      Peak forces ranged from 880 to 202 N for heavy thrusts and 322- to 66 N for light
      thrusts. Thrust rate was from 8.1 to 1.8 Newtons per millisecond. Average
      coefficients of variability (CV = STD/mean) at each load level (initial/final)
      were heavy: 17%/15%; normal: 16%/15%; and light: 20%/20%, with 0 as ideal. A
      force ratio measured students' abilities to distinguish thrust magnitude. The
      heavy/normal ratio (initial/final) was 1.35/1.39, and the light/normal ratio was
      0.70/0.67. CONCLUSIONS: At this point, without force feedback being used in the
      classroom, novice students can produce thrusts that look like those of their
      teachers and of experienced practitioners, but they may not produce similar speed
      and force values. They are consistent within and between sessions and can
      discriminate between light and heavy loads. A natural next step in our
      educational research will be to measure adjustment factors on more experienced
      cohorts of students with and without the presence of force-feedback training
      apparatus.

PMID- 28768117
TI  - Cationic surfactant mediated fibrillogenesis in bovine liver catalase: a
      biophysical approach.
AB  - Protein aggregation into oligomers and mature fibrils are associated with more
      than 20 diseases in humans. The interactions between cationic surfactants
      dodecyltrimethylammonium bromide (DTAB) and tetradecyltrimethylammonium bromide
      (TTAB) with varying alkyl chain lengths and bovine liver catalase (BLC) were
      examined by various biophysical approaches. The delicate coordination of
      electrostatic and hydrophobic interactions with protein, play imperative role in
      aggregation. In this article, we have reconnoitered the relation between charge,
      hydrophobicity and cationic surfactants DTAB and TTAB on BLC at pH 7.4 and 9.4
      which are two and four units above pI, respectively. We have used techniques like
      turbidity, Rayleigh light scattering, far-UV CD, ThT, ANS, Congo red binding
      assay, DLS, and transmission electron microscopy. The low concentration ranges of
      DTAB (0-600 MUM) and TTAB (0-250 MUM) were observed to increase aggregation at pH
      9.4. Nevertheless, at pH 7.4 only TTAB was capable of inducing aggregate. DTAB
      did not produce any significant change in secondary structure at pH 7.4
      suggestive of the role of respective charges on surfactants and protein according
      to the pI and alkyl chain length. The morphology of aggregates was further
      determined by TEM, which proved the existence of a fibrillar structure. The
      surfactants interaction with BLC was primarily electrostatic as examined by ITC.
      Our work demystifies the critical role of charge as well as hydrophobicity in
      amyloid formation.

PMID- 28768116
TI  - On Reproductive Work in Spain: Transnational Adoption, Egg Donation, Surrogacy.
AB  - Spain's plummeting fertility since the late twentieth century may seem to reflect
      a waning desire for children. Nevertheless, reproductive disappointments
      resulting from gender inequalities cause many Spanish women to postpone
      motherhood and experience age-related fertility problems. For them, creating a
      family often becomes possible only through the reproductive labor of other women.
      Our analysis of transnational adoption, egg donation, and surrogacy in Spain
      shows how anonymity and altruism play out in these three strategies, with
      implications for the valuation of women's reproductive work and relationships
      among reproductive providers, intermediaries, recipients, and the resulting
      children.

PMID- 28768118
TI  - An Imaged-Based Three-Dimensional Study of First Metatarsal Protrusion Distance
      in Women with and Without Hallux Valgus.
AB  - BACKGROUND: First metatarsal protrusion distance (MPD) has been commonly studied
      as a characteristic of hallux valgus deformity. To date, the majority of
      investigations have used radiographic methods, with most reporting first
      metatarsal (ray) protrusion to be associated with deformity. As an alternative,
      this study used a three-dimensional (3-D) image acquisition and data analysis
      method to quantify MPD. METHODS: Magnetic resonance images were acquired in
      weightbearing on 29 women (19 with hallux valgus; 10 controls). After the 3-D
      images were reconstructed into virtual bone models, two examiners measured MPD in
      relation to the navicular. In addition to a reliability analysis, a t test
      assessed for group differences in demographics, foot posture (hallux valgus,
      intermetatarsal angles), and MPD. RESULTS: Group demographics were not different,
      while measures of hallux valgus and intermetatarsal angles were different ( P <
      0.01) between groups. The measurement of MPD was highly reliable (ICC [Formula:
      see text] 0.99; SEM [Formula: see text] 0.78 mm). Metatarsal protrusion averaged
      approximately -2.0 mm in both groups. There was no statistical group difference (
      P = 0.89) in MPD. CONCLUSIONS: The reconstructed image datasets captured the 3-D
      spatial relationship of the anatomy. Measurements of MPD were reliable. The first
      ray measured 2 mm shorter than the second ray in both the hallux valgus and
      control groups. Though unexpected, this result may prompt future study of the
      pathokinematics associated with hallux valgus that include the quantification of
      metatarsal protrusion with 3-D methods, instead of relying solely on single-plane
      radiograph reports.

PMID- 28768119
TI  - CDC Screening Recommendation for Baby Boomers and Hepatitis C Virus Testing in
      the US Military Health System.
AB  - OBJECTIVES: Chronic hepatitis C virus (HCV) is the most common blood-borne
      infection in the United States, with an estimated 2.7 to 3.9 million cases as of
      2014. In August 2012, the Centers for Disease Control and Prevention (CDC)
      recommended 1-time HCV testing of all baby boomers. The objectives of this study
      were to (1) determine the proportion of people screened for HCV in the US
      Department of Defense Military Health System before and after the CDC screening
      recommendation for baby boomers and (2) assess whether certain patient or system
      factors were associated with screening for HCV before and after August 2012.
      METHODS: We used a dataset containing 5% of beneficiaries randomly selected from
      the Military Health System Data Repository medical claims database for the period
      July 2011 through September 2013. RESULTS: Of 108 223 people eligible for HCV
      screening during the first period (July 2011 through July 2012), 1812 (1.7%) were
      screened. Of 109 768 people eligible during the second period (September 2012
      through September 2013), 2599 (2.4%) were screened. HCV screening receipt was
      related to benefit type (Prime before August 2012: adjusted odds ratio [aOR] =
      2.16; 95% confidence interval [CI], 1.89-2.46; Prime after August 2012: aOR =
      1.93; 95% CI, 1.73-2.16) and care source (direct care before August 2012: aOR =
      1.80; 95% CI, 1.57-2.07; direct care after August 2012: aOR = 2.45; 95% CI, 2.18
      2.75); male sex (aOR = 1.17; 95% CI, 1.06-1.29) and black race (aOR = 1.20; 95%
      CI, 1.05-1.37) were associated with HCV testing only before August 2012.
      CONCLUSIONS: Interventions should be implemented to increase awareness and
      knowledge of the current national HCV testing recommendation among baby boomers
      to seek out testing and health care providers to perform screening.

PMID- 28768120
TI  - Investigation of Lung Pharmacokinetic of the Novel PDE4 Inhibitor CHF6001 in
      Preclinical Models: Evaluation of the PreciseInhale Technology.
AB  - BACKGROUND: Preclinical evaluation of new chemical entities (NCEs) designed to be
      administered by inhalation route requires lung administration to rodents,
      especially in the discovery phase. Different administration methods have been
      used until now, but more efforts are required to obtain controlled and
      reproducible lung deposition when only small amounts of neat powder material are
      available. METHODS: The PreciseInhale platform used in the present study enables
      well-controlled powder aerosol exposures with only small amounts of micronized
      neat material, providing data on inhalation pharmacokinetic (PK) of NCEs at a
      very early stage. The DustGun aerosol technology uses compressed air to generate
      a respirable aerosol from milligram-amounts of powder that is delivered to one
      animal at a time. The new methodology was used to investigate the inhalation PK
      and lung retention in the rat of the novel Chiesi PDE4 inhibitor CHF6001 in three
      exposure models of the PreciseInhale platform: nose-only, intratracheally
      intubated rat, and the isolated, ventilated, and perfused rat lung. Results were
      compared with data from two other pulmonary delivery systems commonly used in
      preclinical studies: liquid instillation and powder insufflation. RESULTS:
      Administration of micronized CHF6001 using the PreciseInhale system yielded lung
      exposures in the same range as the other tested devices, but the reproducibility
      in lung deposition was improved. The initial amount of CHF6001 in lungs at the
      first sampling time point was close to the predetermined target dose. Tracheal
      deposition with PreciseInhale (0.36 +/- 0.22 MUg) was significantly less than
      with other tested delivery systems: PennCentury (23.7 +/- 3.2 MUg) and Airjet
      (25.6 +/- 7.2 MUg). CONCLUSIONS: The PreciseInhale platform enabled the
      administration of CHF6001 powder with good accuracy and reproducibility, with low
      tracheal deposition. The new platform can be used at an early discovery stage to
      obtain inhalatory PK data for respirable aerosols of neat NCE powder without
      excipients and with minimal use of dry powder formulation work.

PMID- 28768121
TI  - Dealing With Moral Dilemmas at the Neonatology Ward: The Importance of Joint Case
      by-Case Reflection.

PMID- 28768123
TI  - The Concept of "Continuing Creation" Will Not Save Us From Difficult Decisions.

PMID- 28768124
TI  - Rock the Baby, Not the Boat: A Defense of Epidemiology-Based and Values-Based
      Shared Decision Making at the Margin of Gestational Viability.

PMID- 28768125
TI  - Perpetuating Biases and Injustice Toward Preterm Infants.

PMID- 28768126
TI  - Getting Clear on Why the Benefits of Existence Do Not Compel Us to Create.

PMID- 28768127
TI  - "Save or Create": The Practical Asymmetry of Judgment Training in Decision Making
      in Neonatology-When Basic Desires Clash With Preparation to Act.

PMID- 28768128
TI  - The Advance of Rescue Technologies and the Border of Viability.

PMID- 28768129
TI  - How We Should Conceive of Creation: Natural Birth as an Ethical Guidepost for
      Neonatal Rescue.

PMID- 28768130
TI  - Taking Care of the Vulnerable: The Criterion of Proportionality.

PMID- 28768131
TI  - What We Do When We Resuscitate Extremely Preterm Infants.

PMID- 28768132
TI  - The Saving/Creating Distinction and the Axiology of the Cost-Benefit Approach to
      Neonatal Medicine.

PMID- 28768133
TI  - Metaphors in the Management of Extremely Preterm Birth.

PMID- 28768134
TI  - Saving or Creating: Which Are We Doing When We Resuscitate Extremely Preterm
      Infants?
AB  - Neonatal intensive care units represent simultaneously one of the great success
      stories of modern medicine, and one of its most controversial developments. One
      particularly controversial issue is the resuscitation of extremely preterm
      infants. Physicians in the United States generally accept that they are required
      to resuscitate infants born as early as 25 weeks and that it is permissible to
      resuscitate as early as 22 weeks. In this article, I question the moral pressure
      to resuscitate by criticizing the idea that resuscitation in this context "saves"
      a human life. Our radical medical advancements have allowed us to intervene in
      the life of a human before it makes sense to say that such an intervention
      "saves" someone; rather, what the physician does in resuscitating and treating an
      extremely preterm infant is to take over creating it. This matters, I argue,
      because "rescues" are much more morally urgent than "creations."

PMID- 28768136
TI  - Asymmetrical Reasons, Newborn Infants, and Resource Allocation.

PMID- 28768138
TI  - Saving or Creating: Expertise and Subjectivity.

PMID- 28768139
TI  - Extreme Prematurity: Creating "Iatrogenic Lives".

PMID- 28768140
TI  - On Saving Preterm Infants: A Plea for Sensible Ontology.

PMID- 28768141
TI  - A Randomized Trial to Assess the Effect of Fluoroquinolone Metaphylaxis on the
      Fecal Prevalence and Quinolone Susceptibilities of Salmonella and Campylobacter
      in Feedlot Cattle.
AB  - The study objective was to determine effects of fluoroquinolone metaphylaxis on
      fecal prevalence of Salmonella and Campylobacter and fecal prevalence of
      quinolone-resistant Salmonella and Campylobacter in feedlot cattle. On Day 0,
      cattle (n = 288) at risk for bovine respiratory disease (BRD) were randomly
      assigned to either a nontreated control pen (12 pens) or a fluoroquinolone
      treated (enrofloxacin; Baytril(r) 100) pen (12 pens). Rectal fecal samples were
      collected from cattle on days 0, 7, 14, 21, and 28. Feces were cultured for
      Salmonella enterica and Campylobacter spp. using enrichment and selective
      isolation methods, and confirmed by serology and PCR. Susceptibilities to
      nalidixic acid and ciprofloxacin were determined using microbroth dilution
      methods. Data analyses were performed using linear mixed models. Overall,
      Salmonella sp. and Campylobacter spp. were recovered from 10.2% (139/1,364) and
      12.4% (170/1,364) of the fecal samples, respectively. Campylobacter species
      included hyointestinalis, jejuni, and coli. Neither Salmonella sp. nor
      Campylobacter spp. prevalence was significantly impacted by fluoroquinolone
      treatment (p = 0.80, p = 0.61, respectively). However, Salmonella prevalence
      differed between study weeks (p < 0.01) with prevalence decreasing over time.
      Before treatment, 98.9% (91/92) of Salmonella isolates were susceptible to
      nalidixic acid and ciprofloxacin. All Salmonella recovered posttreatment (n = 43)
      were susceptible to both antimicrobials. The majority of Campylobacter spp.
      recovered before treatment were resistant to nalidixic acid (23/35; 65.7%) and
      ciprofloxacin (21/35; 60.0%). There was no significant treatment by week
      interaction (p = 0.85) or treatment effects (p = 0.61) on the posttreatment
      prevalence of Campylobacter resistance. There was, however, a significant week
      effect (p = 0.05), with Campylobacter resistance prevalence decreasing over time.
      In this 28-day study, we found no evidence that a fluoroquinolone used for
      metaphylaxis significantly impacts fecal prevalence of Salmonella sp. or
      Campylobacter spp. or the fecal prevalence of nalidixic acid or ciprofloxacin
      resistance.

PMID- 28768142
TI  - Contributions of IKZF1, DDC, CDKN2A, CEBPE, and LMO1 Gene Polymorphisms to Acute
      Lymphoblastic Leukemia in a Yemeni Population.
AB  - BACKGROUND: Genome-wide and candidate gene association studies have previously
      revealed links between a predisposition to acute lymphoblastic leukemia (ALL) and
      genetic polymorphisms in the following genes: IKZF1 (7p12.2; ID: 10320), DDC
      (7p12.2; ID: 1644), CDKN2A (9p21.3; ID: 1029), CEBPE (14q11.2; ID: 1053), and
      LMO1 (11p15; ID: 4004). In this study, we aimed to conduct an investigation into
      the possible association between polymorphisms in these genes and ALL within a
      sample of Yemeni children of Arab-Asian descent. METHODS: Seven single-nucleotide
      polymorphisms (SNPs) in IKZF1, three SNPs in DDC, two SNPs in CDKN2A, two SNPs in
      CEBPE, and three SNPs in LMO1 were genotyped in 289 Yemeni children (136 cases
      and 153 controls), using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic
      Array). Logistic regression analyses were used to estimate ALL risk, and the
      strength of association was expressed as odds ratios with 95% confidence
      intervals. RESULTS: We found that the IKZF1 SNP rs10235796 C allele (p = 0.002),
      the IKZF1 rs6964969 A>G polymorphism (p = 0.048, GG vs. AA), the CDKN2A rs3731246
      G>C polymorphism (p = 0.047, GC+CC vs. GG), and the CDKN2A SNP rs3731246 C allele
      (p = 0.007) were significantly associated with ALL in Yemenis of Arab-Asian
      descent. In addition, a borderline association was found between IKZF1 rs4132601
      T>G variant and ALL risk. No associations were found between the IKZF1 SNPs
      (rs11978267; rs7789635), DDC SNPs (rs3779084; rs880028; rs7809758), CDKN2A SNP
      (rs3731217), the CEBPE SNPs (rs2239633; rs12434881) and LMO1 SNPs (rs442264;
      rs3794012; rs4237770) with ALL in Yemeni children. CONCLUSION: The IKZF1 SNPs,
      rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported)
      could serve as risk markers for ALL susceptibility in Yemeni children.

PMID- 28768143
TI  - Intrauterine exposure to 17beta-oestradiol (E2) impairs postnatal development in
      both female and male prostate in gerbil.
AB  - We employed histological techniques to assess the effects of intrauterine
      exposure to different dosages of E2 on male and female Mongolian gerbils on the
      postnatal development of the prostate. E2 promotes alterations this gland
      branches in the female, but not in males, even at low dosage, at higher dosages,
      acini of altered aspect are verified in the male and female prostate, as well as
      a decrease in branching number, reduced cell proliferation and staining for
      FGF10, simultaneously to the increased labelling for TGFbeta1, which may account
      for alterations on branching of the prostate. The sensitivity of the female
      prostate to intrauterine exposure to E2, which can reflect the E2 dependence of
      female prostate development. This becomes alarming in view of the occurrence of
      prostate in female of several mammals and including women, and the possibility
      that low E2 dosage exposures considered safe to males provoke developmental
      alterations in female prostate.

PMID- 28768145
TI  - Stay connected: Electrical conductivity of microbial aggregates.
AB  - The discovery of direct extracellular electron transfer offers an alternative to
      the traditional understanding of diffusional electron exchange via small
      molecules. The establishment of electronic connections between electron donors
      and acceptors in microbial communities is critical to electron transfer via
      electrical currents. These connections are facilitated through conductivity
      associated with various microbial aggregates. However, examination of
      conductivity in microbial samples is still in its relative infancy and conceptual
      models in terms of conductive mechanisms are still being developed and debated.
      The present review summarizes the fundamental understanding of electrical
      conductivity in microbial aggregates (e.g. biofilms, granules, consortia, and
      multicellular filaments) highlighting recent findings and key discoveries. A
      greater understanding of electrical conductivity in microbial aggregates could
      facilitate the survey for additional microbial communities that rely on direct
      extracellular electron transfer for survival, inform rational design towards the
      aggregates-based production of bioenergy/bioproducts, and inspire the
      construction of new synthetic conductive polymers.

PMID- 28768144
TI  - The C-terminal domain of zDHHC2 contains distinct sorting signals that regulate
      intracellular localisation in neurons and neuroendocrine cells.
AB  - The S-acyltransferase zDHHC2 mediates dynamic S-acylation of PSD95 and
      AKAP79/150, which impacts synaptic targeting of AMPA receptors. zDHHC2 is
      responsive to synaptic activity and catalyses the increased S-acylation of PSD95
      that occurs following action potential blockade or application of ionotropic
      glutamate receptor antagonists. These treatments have been proposed to increase
      plasma membrane delivery of zDHHC2 via an endosomal cycling pathway, enhancing
      substrate accessibility. To generate an improved understanding of zDHHC2
      trafficking and how this might be regulated by neuronal activity, we searched for
      intramolecular signals that regulate enzyme localisation. Two signals were mapped
      to the C-terminal tail of zDHHC2: a non-canonical dileucine motif [SxxxLL] and a
      downstream NP motif. Mutation of these signals enhanced plasma membrane
      accumulation of zDHHC2 in both neuroendocrine PC12 cells and rat hippocampal
      neurons, consistent with reduced endocytic retrieval. Furthermore, mutation of
      these signals also increased accumulation of the enzyme in neurites.
      Interestingly, several threonine and serine residues are adjacent to these
      sorting motifs and analysis of phospho-mimetic mutants highlighted a potential
      role for phosphorylation in regulating the efficacy of these signals. This study
      offers new molecular insight into the signals that determine zDHHC2 localisation
      and highlights a potential mechanism to regulate these trafficking signals.

PMID- 28768146
TI  - Diosmin prevents left ventricular hypertrophy, adenosine triphosphatases
      dysfunction and electrolyte imbalance in experimentally induced myocardial
      infarcted rats.
AB  - Currently, there has been an increased interest globally to identify natural
      compounds that are pharmacologically potent and have low or no adverse effects
      for use in preventive medicine. Myocardial infarction is a vital pathological
      feature resulting in high levels of mortality and morbidity. Left ventricular
      hypertrophy (LVH), adenosine triphosphatases (ATPases) dysfunction and
      electrolyte imbalance play a vital role in the pathogenesis of myocardial
      infarction. This study aims to evaluate the preventive effects of diosmin on LVH,
      ATPases dysfunction and electrolyte imbalance in isoproterenol induced myocardial
      infarcted rats. Male albino Wistar rats were pretreated orally with diosmin
      (10mg/kg body weight) daily for a period of 10 days. After pretreatment,
      isoproterenol (100mg/kg body weight) was injected subcutaneously into the rats
      twice at an interval of 24h to induce myocardial infarction. Isoproterenol
      induced myocardial infarcted rats showed increased LVH, altered levels/
      concentrations of serum cardiac troponin-T, heart ATPases, heart sodium ion,
      calcium ion and potassium ion, and increased myocardial infarct size.
      Pretreatment with diosmin revealed preventive effects on LVH, and all the above
      mentioned biochemical parameters evaluated in isoproterenol induced myocardial
      infarcted rats. The 2, 3, 5-triphenyl tetrazolium chloride staining on myocardial
      infarct size confirmed the prevention of myocardial infarction. Further, the 1, 1
      diphenyl-2- picryl-hydrazyl (DPPH) radical in vitro study revealed a potent DPPH
      free radical scavenging action of diosmin. Thus, the observed effects of diosmin
      are due to its antihypertrophic and free radical scavenging activities in
      isoproterenol induced myocardial infarcted rats.

PMID- 28768147
TI  - Production of human recombinant phenylalanine hydroxylase in Lactobacillus
      plantarum for gastrointestinal delivery.
AB  - Phenylketonuria (PKU) is an autosomal recessive disorder caused by a defective
      phenylalanine hydroxylase (PAH), which catalyzes the hydroxylation of l
      phenylalanine (l-Phe) to l-tyrosine (l-Tyr) in presence of the cofactor
      tetrahydrobiopterin (BH4). Defective PAH causes accumulation of phenylalanine,
      which has neurotoxic effects and leads to dermatological, behavioral, and
      neurocognitive problems. Treatments for this disease consist in life-long diets
      that are hard for patients to keep, or supplementation with BH4. In this study,
      we propose a system where a probiotic lactic acid bacteria (LAB) can be used as
      vehicle to express in situ an engineered human PAH. Engineered PAHs contain a
      secretion peptide, a gastrointestinal signal (GI), the human PAH, and a flexible
      glycine linker followed by the fluorescence protein mEGFP. Engineered constructs
      were successfully transformed, expressed, and secreted in Lactobacillus plantarum
      CM_PUJ411. PAH construct containing either the signal peptide GI1 or GI2 were
      transported through a Caco-2 cell monolayer. Nevertheless, the one containing GI1
      allowed the highest transport through the cell monolayer. Co-culture of L.
      plantarum and Caco-2 cells showed that engineered PAH is produced in-situ and
      transported through the cell monolayer. Finally, the activity test showed that
      the engineered PAH secreted by L. plantarum CM_PUJ411 is active, leading to a
      reduction in l-Phe and an increase in l-Tyr levels, respectively. These results
      show the potential of this system as a new therapeutic alternative for the
      treatment of PKU patients.

PMID- 28768148
TI  - Over two decades of Plasmodium knowlesi infections in Sarawak: Trend and
      forecast.
AB  - Malaria is still of great public health concern, especially in Malaysian Borneo.
      The aim of this study was to determine the trends of P. knowlesi infection in
      Sarawak, Malaysia and to forecast the incidence of P. knowlesi until the year
      2040. Data on P. knowlesi malaria cases from 1992 to the year 2014 were obtained
      from the Sarawak Health Department, Malaysia. ARIMA model was applied to forecast
      the future incidence of P. knowlesi infection. The data for the whole of Sarawak
      and subsequently the selected six districts which have high incidence rates of P.
      knowlesi infection were analyzed. Results of the analysis showed that there was
      an increasing trend of P. knowlesi cases from the year 1992-2014 (p<0.001). The
      trend in the incidence started to increase in the year 2008 (p=0.029). The
      incidence rate per 100,000 populations was between 4.15 in the year 1992 and
      42.03 in the year 2014. High incidence of P. knowlesi infections has been
      detected in the districts adjacent to each other within the interior region of
      Sarawak. The forecasted incidence and incidence rate per 100,000 populations in
      the year 2020 were 1229 and 44.04, respectively, while those in the year 2040
      were 2056 and 62.91, respectively. The forecasted incidence showed an upward
      trend highlighting an urgent need to draw up strategic and holistic prevention
      plans to limit further the increase in P. knowlesi morbidity and mortality in
      Sarawak. It is imperative that these measures are customized taking into
      consideration the challenges faced in the interior areas of Sarawak and the
      behavior of the main vector of P. knowlesi (i.e., An. latens) in Sarawak.

PMID- 28768150
TI  - Biotransformation of drospirenone, a contraceptive drug, with Cunninghamella
      elegans.
AB  - Biotransformation of an orally active contraceptive drug, drospirenone (1), by
      Cunninghamella elegans ATCC 36114 yielded four new metabolites,
      6beta,7beta,15beta,16beta-dimethylene-3-oxo-14alpha-hydroxy-17alpha-pregn-4-ene
      21,17-carbolactone (2), 6beta,7beta,15beta,16beta-dimethylene-3,11-dioxo-17alpha
      pregn-4-ene-21,17-carbolactone (3), 6beta,7beta,15beta,16beta-dimethylene-3,12
      dioxo-17alpha-pregn-4-ene-21,17-carbolactone (4), and 6beta,7beta,15beta,16beta
      dimethylene-3-oxo-11beta,14alpha-dihydroxy-17alpha-pregn-4-ene-21,17-carbolactone
      (5), along with a known metabolite, 6beta,7beta,15beta,16beta-dimethylene-3-oxo
      11alpha-dihydroxy-17alpha-pregn-4-ene-21,17-carbolactone (6). This study provides
      not only new analogues of orally active contraceptive drug, drospirenone, but
      also help in understanding the metabolism of this important drug.

PMID- 28768151
TI  - Tuned by experience: How orientation probability modulates early perceptual
      processing.
AB  - Probable stimuli are more often and more quickly detected. While stimulus
      probability is known to affect decision-making, it can also be explained as a
      perceptual phenomenon. Using spatial gratings, we have previously shown that
      probable orientations are also more precisely estimated, even while participants
      remained naive to the manipulation. We conducted an electrophysiological study to
      investigate the effect that probability has on perception and visual-evoked
      potentials. In line with previous studies on oddballs and stimulus prevalence,
      low-probability orientations were associated with a greater late positive 'P300'
      component which might be related to either surprise or decision-making. However,
      the early 'C1' component, thought to reflect V1 processing, was dampened for high
      probability orientations while later P1 and N1 components were unaffected.
      Exploratory analyses revealed a participant-level correlation between C1 and P300
      amplitudes, suggesting a link between perceptual processing and decision-making.
      We discuss how these probability effects could be indicative of sharpening of
      neurons preferring the probable orientations, due either to perceptual learning,
      or to feature-based attention.

PMID- 28768149
TI  - The biological foundation of the genetic association of TOMM40 with late-onset
      Alzheimer's disease.
AB  - A variable-length poly-T variant in intron 6 of the TOMM40 gene, rs10524523, is
      associated with risk and age-of-onset of sporadic (late-onset) Alzheimer's
      disease. In Caucasians, the three predominant alleles at this locus are Short
      (S), Long (L) or Very long (VL). On an APOE epsilon3/3 background, the S/VL and
      VL/VL genotypes are more protective than S/S. The '523 poly-T has regulatory
      properties, in that the VL poly-T results in higher expression than the S poly-T
      in luciferase expression systems. The aim of the current work was to identify
      effects on cellular bioenergetics of increased TOM40 protein expression.
      MitoTracker Green fluorescence and autophagic vesicle staining was the same in
      control and over-expressing cells, but TOM40 over-expression was associated with
      increased expression of TOM20, a preprotein receptor of the TOM complex, the
      mitochondrial chaperone HSPA9, and PDHE1a, and increased activities of the
      oxidative phosphorylation complexes I and IV and of the TCA member alpha
      ketoglutaric acid dehydrogenase. Consistent with the complex I findings,
      respiration was more sensitive to inhibition by rotenone in control cells than in
      the TOM40 over-expressing cells. In the absence of inhibitors, total cellular
      ATP, the mitochondrial membrane potential, and respiration were elevated in the
      over-expressing cells. Spare respiratory capacity was greater in the TOM40 over
      expressing cells than in the controls. TOM40 over-expression blocked Ab-elicited
      decreases in the mitochondrial membrane potential, cellular ATP levels, and
      cellular viability in the control cells. These data suggest elevated expression
      of TOM40 may be protective of mitochondrial function.

PMID- 28768152
TI  - Mechanosensing in liver regeneration.
AB  - Liver is highly regenerative as it can restore its function and size even after
      70% partial hepatectomy. During liver regeneration, the mechanical and chemical
      environment of liver is altered with accumulation of various growth factors and
      remodeling of extracellular environment. Cells can sense the changes in their
      cellular environment through various chemo and mechanosensors present on their
      surfaces. These changes are then transduced by initiation of multiple signaling
      pathways. Traditional view of liver regeneration describes the process as a
      cascade of chemical signaling pathways. In this review, we describe the role of
      mechanical forces and mechanosensing in regulating liver regeneration with focus
      on the role of altered shear and extracellular matrix environment following
      injury. These mechanosensing mechanisms either generate molecular signals that
      further activate downstream signaling pathways such as YAP or directly transduce
      mechanical signals by regulating actomyosin cytoskeleton. These signals travel to
      the decision center such as nucleus to switch cell fate and activate functions
      needed in liver regeneration, e.g. proliferation of various hepatic cell types,
      differentiation of hepatic stem cells, extracellular matrix remodeling and
      termination signals that regulate the regenerated liver size. Different
      mechanical and chemical signals coordinate intracellular chemical signaling
      pathways leading to robust liver regeneration.

PMID- 28768153
TI  - Effects of mechanical ventilation on gene expression profiles in renal allografts
      from brain dead rats.
AB  - Pathophysiological changes of brain death (BD) are impairing distal organ
      function and harming potential renal allografts. Whether ventilation strategies
      influence the quality of renal allografts from BD donors has not been thoroughly
      studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no
      brain death (NBD) with low tidal volume/low positive endexpiratory pressure
      (PEEP) titrated to minimal static elastance of the respiratory system
      (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death
      (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. We hypothesized that HVT/LPEEP in
      BD leads to increased interleukin 6 (IL-6) gene expression and impairs potential
      renal allografts after six hours of mechanical ventilation. We assessed
      inflammatory cytokines in serum, genome wide gene expression profiles and
      quantitative PCR (qPCR) in kidney tissue. The influence of BD on renal gene
      expression profiles was greater than the influence of the ventilation strategy.
      In BD, LVT ventilation did not influence the inflammatory parameters or kidney
      function in our experimental model.

PMID- 28768154
TI  - Binding effect of fluorescence labeled glycyrrhetinic acid with GA receptors in
      hepatocellular carcinoma cells.
AB  - Glycyrrhetinic acid (GA) is a natural active component from licorice, which is
      broadly used in traditional Chinese medicine. Lots of glycyrrhetinic acid
      receptors (GA-R) are proved to locate on the surface of liver cells. Many reports
      about the hepatocellular carcinoma (HCC) treatment were dependent on GA modified
      carriers. However, the reality of GA-R in HCC cells was not clear. In this paper,
      18beta-glycyrrhetinic acid (18beta-GA) was labeled with fluorescence (FITC) by
      chemical synthesis. Together with the binding effect of fluorescence labeled
      glycyrrhetinic acid (FITC-GA), the competitive action of 18beta-GA with GA-R was
      investigated in HCC cells. The results showed that in HepG2 cells, 18beta-GA and
      FITC-GA presented similar cytotoxicity. The specific binding saturation of GA
      showed the dissociation constant (Kd) was 7.457+/-2.122pmol/L and the maximum
      binding counts (Bmax) was 2.385+/-0.175pmol/2.5*106 cells, respectively. FITC-GA
      bound to cytomembrane specifically and 18beta-GA competed to bind the sites
      significantly in HepG2 cells. Therefore, there is binding effect between
      fluorescence labeled GA and GA-R. The GA-R on HCC cells is confirmed as expected,
      which provides a useful reference of active target modified by GA and a novel
      approach for receptors and ligands study.

PMID- 28768155
TI  - The role of the intrinsic cholinergic system of the striatum: What have we
      learned from TAN recordings in behaving animals?
AB  - Cholinergic interneurons provide rich local innervation of the striatum and play
      an important role in controlling behavior, as evidenced by the variety of
      movement and psychiatric disorders linked to disrupted striatal cholinergic
      transmission. Much progress has been made in recent years regarding our
      understanding of how these interneurons contribute to the processing of
      information in the striatum. In particular, investigation of the activity of
      presumed striatal cholinergic interneurons, identified as tonically active
      neurons or TANs in behaving animals, has pointed to their role in the signaling
      and learning of the motivational relevance of environmental stimuli. Although the
      bulk of this work has been conducted in monkeys, several studies have also been
      carried out in behaving rats, but information remains rather disparate across
      studies and it is still questionable whether rodent TANs correspond to TANs
      described in monkeys. Consequently, our current understanding of the function of
      cholinergic transmission in the striatum is challenged by the rapidly growing,
      but often confusing literature on the relationship between TAN activity and
      specific behaviors. As regards the precise nature of the information conveyed by
      the cholinergic TANs, a recent influential view emphasized that these local
      circuit neurons may play a special role in the processing of contextual
      information that is important for reinforcement learning and selection of
      appropriate actions. This review provides a summary of recent progress in TAN
      physiology from which it is proposed that striatal cholinergic interneurons are
      crucial elements for flexible switching of behaviors under changing environmental
      conditions.

PMID- 28768156
TI  - The Syk kinases orchestrate cerebellar granule cell tangential migration.
AB  - The tyrosine kinases of the Syk family are essential components of the well
      characterized immunoreceptor ITAM-based signaling pathway. However, ITAM-based
      signaling typically does not function in isolation. Instead, it is enmeshed in
      the molecular network controlling cellular adhesion and chemotaxis. Consistent
      with the increasing number of data involving ITAM-bearing molecules in neuronal
      functions, we previously depicted a role for Syk kinases in the establishment of
      neuronal connectivity. In the developing cerebellum, we found that Syk is
      essentially expressed in the granule cells (GC) and more importantly,
      phosphorylated on tyrosine residues representative of an active form of the
      kinase in tangentially migrating GC. In light of these findings, experiments were
      performed to establish the implication of Syk in this process. We showed that Syk
      state of phosphorylation is spatiotemporally regulated during GC ontogeny.
      Moreover, the analysis of external granular layer microexplants treated with a
      Syk pharmacological inhibitor together with the quantification of ectopic GC in
      Syk+/-; ZAP-70-/- mutant mice brought evidence of a requirement of Syk in GC
      tangential migration. Syk phosphorylation was induced by EphB2 engagement and
      locally turned down by a not yet identified factor that could in part explain the
      restricted pattern of Syk phosphorylation observed along GC migratory route.
      Whereas Syk kinase activity appeared not essential for ephrin/Eph-mediated axon
      extension, it might provide polarization signals required for proper nucleus
      translocation during GC migration. In conclusion, Syk kinase acts downstream of
      receptors controlling GC tangential migration.

PMID- 28768157
TI  - Neurofeedback of SMR and Beta1 Frequencies: An Investigation of Learning Indices
      and Frequency-Specific Effects.
AB  - Despite evidence that Sensorimotor Rhythm (SMR) and beta1 neurofeedback have
      distinct cognitive enhancement effects, it remains unclear whether their
      amplitudes can be independently enhanced. Furthermore, demands for top-down
      attention control, postural restraint and maintenance of cognitive set processes,
      all requiring low-beta frequencies, might masquerade as learning and confound
      interpretation. The feasibility of selectively enhancing SMR and beta1 amplitudes
      was investigated with the addition of a random frequency control condition that
      also requires the potentially confounding cognitive processes. A comprehensive
      approach to assessing neurofeedback learning was undertaken through the
      calculation of learning indices within- and across-session and pre-to-post
      baseline. Herein we provide the first demonstration of beta1 within-session
      amplitude learning that was not attributable to extraneous cognitive processes,
      for it was not found with random frequency training. On the other hand, within
      session SMR learning might have been obscured by high interindividual variability
      and methodological limitations such as the type of feedback screen, the
      insufficient number of sessions, and the exclusion of simultaneous theta and high
      beta inhibition. Interestingly, SMR and beta1 amplitude increased across sessions
      in the three groups suggesting unspecific effects of neurofeedback in the low
      beta frequency band. Moreover, there was no clear evidence of frequency
      specificity associated with either SMR or beta1 training. Some methodological
      limitations may underpin the divergent results with previous studies.

PMID- 28768158
TI  - Differential effects of stress on fear learning and activation of the amygdala in
      pre-adolescent and adult male rats.
AB  - Adolescence is accompanied by the maturation of several stress-responsive areas
      of the brain including the amygdala, a key region for the acquisition and
      expression of conditioned fear. These changes may contribute to the development
      of stress-related disorders in adolescence, such as anxiety and depression, and
      increase the susceptibility to these psychopathologies later in life. Here, we
      assessed the effects of acute restraint stress on fear learning and amygdala
      activation in pre-adolescent and adult male rats. Pre-adolescents exposed to
      stress prior to fear conditioning showed greater resistance to the extinction of
      fear memories than adults. At the cellular level, the combination of stress and
      fear conditioning resulted in a greater number of FOS-positive cells in the
      basolateral nucleus of the amygdala (BLA) than fear conditioning alone, and this
      increase was greater in pre-adolescents than in adults. Despite age-dependent
      differences, we found no changes in glucocorticoid receptor (GR) levels in the
      amygdala of either pre-adolescent or adult males. Overall, our data indicate that
      stress prior to fear conditioning leads to extinction-resistant fear responses in
      pre-adolescent animals, and that the BLA may be one neural locus mediating these
      age-dependent effects of stress on fear learning.

PMID- 28768159
TI  - Hens can ingest extruded polystyrene in rearing buildings and lay eggs
      contaminated with hexabromocyclododecane.
AB  - The overall concentration of hexabromocyclododecane (HBCDD) in eggs is low
      although abnormally high concentrations exceeding 3000 ng g-1 lw have been
      reported. In order to test whether these contaminations may originate from the
      ingestion of insulating materials in rearing buildings, a group of 55 hens raised
      in a collective cage was provided with a 64-g piece of extruded polystyrene (XPS,
      2.59% HBCDD of which 75, 15 and 10% as alpha-, beta- and gamma-HBCDD,
      respectively). Hens entirely consumed the piece within 3 days, leading to a mean
      daily exposure of 4.7 mg HBCDD per kg body weight. Whole egg HBCDD concentration
      reached a maximum of 1037 ng HBCDD g-1 fresh weight (fw), recorded 2 days after
      the piece had disappeared, and decreased down to 86 ng g-1 fw within the 19
      following days. In all these samples, HBCDD was made of 98.7 +/- 0.7 and 1.3 +/-
      0.6% alpha- and beta-HBCDD, respectively, and 0.1% gamma-HBCDD when quantified;
      it was enriched in (-)alpha- and (+)beta-HBCDD with enantiomeric fractions of
      0.438 +/- 0.009 and 0.579 +/- 0.030, respectively. HBCDD was quantified in all
      the individual eggs collected the last day of experiment at concentrations
      ranging between 0.47 and 1361 ng g-1 fw, according to a lognormal distribution.
      The ingestion of XPS in degraded rearing buildings is thus a plausible cause of
      on-farm egg contamination by HBCDD which should be strictly avoided.

PMID- 28768160
TI  - Cytochrome P450 genes from the aquatic midge Chironomus tentans: Atrazine-induced
      up-regulation of CtCYP6EX3 enhanced the toxicity of chlorpyrifos.
AB  - The open reading frames of 19 cytochrome P450 monooxygenase (CYP) genes were
      sequenced from Chironomus tentans, a commonly used freshwater invertebrate model.
      Phylogenetic analysis of the 19 CYPs along with a previously reported CYP
      (CtCYP4G33) revealed that they belong to three different clans, including 3 in
      CYP4, 15 in CYP3, and 2 in mitochondria clan. When third-instar larvae were
      exposed to atrazine at 5000 MUg/L, the transcription of CtCYP6EX3, CtCYP6EV3,
      CtCYP9AT1 and CtCYPEX1 was significantly up-regulated. To examine whether
      CtCYP6EX3 played a role in oxidative activation of chlorpyrifos to chlorpyrifos
      oxon, we evaluated larval susceptibility to chlorpyrifos after CtCYP6EX3
      transcript was suppressed by RNAi. The larvae fed chitosan/dsCtCYP6EX3
      nanoparticles showed a significantly decreased CtCYP6EX3 transcript (53.1%) as
      compared with the control larvae fed chitosan/dsGFP nanoparticles. When the
      CtCYP6EX3-silenced larvae were exposed to chlorpyrifos at 6 MUg/L or its binary
      mixture with atrazine (chlorpyrifos at 3 MUg/L and atrazine at 1000 MUg/L), the
      larvae became less susceptible to the pesticides as their mortalities decreased
      by 24.1% and 20.5%, respectively. These results along with our previous findings
      suggested that the increased toxicity of chlorpyrifos was likely due to an
      enhanced oxidative process from chlorpyrifos to chlorpyrifos-oxon by CtCYP6EX3 as
      RNAi of CtCYP6EX3 led to decreased susceptibility of C. tentans larvae to
      chlorpyrifos alone and the binary mixture of atrazine and chlorpyrifos. However,
      further study would be necessary to validate our results by functional assays
      using heterologously expressed CtCYP6EX3 enzyme.

PMID- 28768161
TI  - Airborne heavy metals in two cities of North Rhine Westphalia - Performing
      inhalation cancer risk assessment in terms of atmospheric circulation.
AB  - The main objective of this study was to examine the levels of four heavy metals
      (As, Cd, Pb and Ni) in PM10 samples collected in two urban background stations in
      Dortmund and Bielefeld, in relation to atmospheric circulation. Pollution roses,
      Conditional Probability Function (CPF) roses and backward air mass trajectory
      clusters were used to identify air currents associated with the importation of
      PM10 and of the included metal constituents. In addition, PM10, NO2, SO2, O3, As,
      Cd, Ni and Pb concentrations were analyzed by a Principal Component Analysis
      (PCA) to reveal major local emission sources of PM10 metal content. Traffic was
      the main emitter of PM10, As, Cd, and Pb in both cities, highlighting the
      existence of non-negligible lead quantities in unleaded gasoline, whilst nickel
      emissions were associated with heavy fuel oil combustion in industries and
      primarily for domestic heating. The created CPF roses and trajectory clusters
      were in good agreement, clearly revealing that eastern air currents enriched the
      locally produced PM10 load with additional aerosols from Eastern Europe. The
      concentrations of arsenic and cadmium were also enhanced by the arrival of air
      parcels from the East, indicating the anthropogenic origin of the exogenous
      aerosols due to combustion. The induced cancer risk (CRinh) for adults, due to
      inhalation of individual metal constituents, was also estimated in terms of
      atmospheric circulation, indicating higher risk in Dortmund than in Bielefeld.
      CRinh values for arsenic exceeded the limit of 1 * 10-6 in both cities, primarily
      during the influence of eastern circulation.

PMID- 28768162
TI  - Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD
      L1/PD-L2.
AB  - Cancer cells can avoid and suppress immune responses through activation of
      inhibitory immune checkpoint proteins, such as PD-1, PD-L1, and CTLA-4. Blocking
      the activities of these proteins with monoclonal antibodies, and thus restoring T
      cell function, has delivered breakthrough therapies against cancer. In this
      review, we describe the latest work on structural characterization of the
      checkpoint proteins, their interactions with cognate ligands and with therapeutic
      antibodies. Structures of the extracellular portions of these proteins reveal
      that they all have a similar modular structure, composed of small domains similar
      in topology to the domains found in antibodies. Structural basis for blocking the
      PD-1/PD-L1 interaction by small molecules is illustrated with the compound BMS
      202 that binds to and induces dimerization of PD-L1.

PMID- 28768163
TI  - A protocol for quantitative analysis of murine and human amyloid-beta1-40 and 1
      42.
AB  - BACKGROUND: Amyloid-beta (Abeta), a hallmark of Alzheimer's disease (AD), has
      long been a focus of basic and translation research in AD. Quantification and
      dissociation of the Abeta fractions in their soluble and insoluble forms, is a
      key factor in numerous AD studies. NEW METHOD: Here we provide a generalized
      sandwich-enzyme-linked-immuno-sorbent-assay (sELISA) protocol for quantification
      of human and murine Abeta1-40 and Abeta1-42 and dissociation of these peptides to
      their soluble-oligomeric and insoluble-fibrillar forms. RESULTS: We have
      validated the levels of soluble and insoluble Abeta1-40 and Abeta1-42 in the
      5XFAD AD and the Ts65Dn Down-Syndrome (DS) mouse models in both the cortex,
      hippocampus and blood as follows: (1) blood levels of Abeta1-40 and Abeta1-42 are
      elevated in both mouse strains. (2) 5XFAD mice exhibit elevated soluble and
      insoluble Abeta1-40 in cortical and hippocampal tissues, soluble Abeta1-42 in the
      hippocampus, and insoluble Abeta1-42in both cortical and hippocampal tissues (3)
      Ts65Dn mice exhibit elevated levels of Abeta1-40 in the cortex. COMPARISON WITH
      EXISTING METHODS: Several methodologies have been proposed for the high
      throughput measure of Abeta, including HPLC-mass-spectrometry, micro
      immunoelectrodes, immunoprecipitation and ELISA. Although commercial sELISA kits
      are widely used, herein, we describe a more accessible and cost-effective in
      house protocol enabling to measure either human or murine, soluble and insoluble
      Abeta1-40 and Abeta1-42 levels. CONCLUSIONS: We provide a streamlined and
      accessible protocol for the assessment of soluble and insoluble Abeta1-40 and
      Abeta1-42 levels from mouse or human origins, enabling a higher accessibility for
      researchers in the field to generate reliable Abeta-related measurements.

PMID- 28768164
TI  - Chronic Sucralose or L-Glucose Ingestion Does Not Suppress Food Intake.
AB  - Despite widespread consumption of non-nutritive sweeteners (NNSs), the impact of
      manipulating the perceived sweetness of food is unclear. Previously we reported
      that chronic consumption of the NNSs sucralose or L-glucose led to increased
      calories consumed post-exposure; however, a recent study suggested this effect
      occurs because NNSs acutely suppress food intake, leading to a caloric debt. Here
      we show that acute ingestion of sucralose in the context of a low-carbohydrate
      diet causes a pronounced increase in calories consumed. Moreover, neither
      sucralose nor L-glucose had a lasting effect on food intake during chronic
      exposure; however, both NNSs enhance food intake post-exposure. Together these
      data confirm that sucralose and L-glucose promote food intake under a variety of
      experimental conditions.

PMID- 28768165
TI  - Plasma Mannose Levels Are Associated with Incident Type 2 Diabetes and
      Cardiovascular Disease.
AB  - Plasma mannose levels are elevated in subjects with insulin resistance
      independently of obesity. Here, we found that elevated plasma mannose levels are
      strong markers of future risk of several chronic diseases including T2D, CVD, and
      albuminuria, and that it may contribute to their development rather than just
      being a novel biomarker.

PMID- 28768166
TI  - Holding Onto Youth.
AB  - Aerobic glycolysis (AG), the synthesis of lactate despite the presence of oxygen,
      has been implicated in the growth of cancer cells, synaptic development, and
      brain plasticity. In this issue of Cell Metabolism, Goyal et al. (2017)
      demonstrate that AG declines with age in the human brain, disappearing almost
      completely by age 60.

PMID- 28768167
TI  - Burning Fat and Building Bone by FSH Blockade.
AB  - The rise of follicle-stimulating hormone (FSH) is a hallmark of menopause
      associated with osteoporosis and visceral adiposity. In Nature, Zaidi and
      colleagues (Liu et al., 2017) report that blocking FSH action reduces body fat by
      promoting brown/beige fat thermogenesis, potentially providing a new intervention
      for the treatment of menopause-related metabolic diseases.

PMID- 28768168
TI  - What's So Special about FGF19-Unique Effects Reported on Skeletal Muscle Mass and
      Function.
AB  - In a recent study published in Nature Medicine, Benoit et al. (2017) reported
      unique effects of FGF19 on mouse skeletal muscle: FGF19 induced skeletal muscle
      hypertrophy and blocked muscle atrophy, acting via FGF receptors and betaKlotho,
      while a related FGF21 hormone was ineffective.

PMID- 28768169
TI  - Once Blind, Now We See GLP-1 Molecular Action.
AB  - The macromolecular mechanics of GLP-1 with its cell surface receptor came into
      focus as two landmark publications recently published in Nature collectively
      herald advancement in structure-based design for a receptor class of great
      therapeutic importance (Jazayeri et al., 2017; Zhang et al., 2017).

PMID- 28768170
TI  - Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal
      Weight in Humans.
AB  - A BMI in the normal range associates with a decreased risk of cardiometabolic
      disease and all-cause mortality. However, not all subjects in this BMI range have
      this low risk. Compared to people who are of normal weight and metabolically
      healthy, subjects who are of normal weight but metabolically unhealthy (~20% of
      the normal weight adult population) have a greater than 3-fold higher risk of all
      cause mortality and/or cardiovascular events. Here we address to what extent
      major risk phenotypes determine metabolic health in lean compared to overweight
      and obese people and provide support for the existence of a lipodystrophy-like
      phenotype in the general population. Furthermore, we highlight the molecular
      mechanisms that induce this phenotype. Finally, we propose strategies as to how
      this knowledge could be implemented in the prevention and treatment of
      cardiometabolic diseases in different stages of adiposity in routine clinical
      practice.

PMID- 28768172
TI  - Sweet Sixteenth for ChREBP: Established Roles and Future Goals.
AB  - With the identification of ChREBP in 2001, our interest in understanding the
      molecular control of carbohydrate sensing has surged. While ChREBP was initially
      studied as a master regulator of lipogenesis in liver and fat tissue, it is now
      clear that ChREBP functions as a central metabolic coordinator in a variety of
      cell types in response to environmental and hormonal signals, with wide
      implications in health and disease. Celebrating its sweet sixteenth birthday, we
      review here the current knowledge about the function and regulation of ChREBP
      throughout usual and less explored tissues, to recapitulate ChREBP's role as a
      whole-body glucose sensor.

PMID- 28768171
TI  - The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway.
AB  - The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of
      cell growth that responds to a diverse set of environmental inputs, including
      amino acids. Over the past 10 years, a number of proteins have been identified
      that help transmit amino acid availability to mTORC1. However, amino acid sensors
      for this pathway have only recently been discovered. Here, we review these recent
      advances and highlight the variety of unexplored questions that emerge from the
      identification of these sensors.

PMID- 28768173
TI  - The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in
      Patients with Type 2 Diabetes.
AB  - Unimolecular dual incretins derived from hybridized glucagon-like peptide 1 (GLP
      1) and glucose-dependent insulinotropic peptide (GIP) sequences have demonstrated
      synergistic reduction of adiposity in animal models and reductions of
      hyperglycemia in short-duration human trials. Here, we extend the
      characterization of NNC0090-2746 (also known as RG7697), a fatty-acylated dual
      agonist possessing in vitro balanced GIPR and GLP-1R agonism. In this 12-week,
      randomized, placebo-controlled, double-blind phase 2a trial, patients with type 2
      diabetes inadequately controlled with metformin received 1.8 mg of NNC0090-2746
      or placebo subcutaneously once daily. Liraglutide 1.8 mg (Victoza), starting with
      2-week dose escalation, was administered subcutaneously once daily as an open
      label reference arm. Measurements were collected at regular intervals after
      randomization. NNC0090-2746 significantly improved glycemic control and reduced
      body weight compared with placebo. Total cholesterol, alone among a range of
      lipid parameters, and leptin were both significantly reduced compared with
      placebo. Treatment with NNC0090-2746 was generally safe and well tolerated.

PMID- 28768174
TI  - Loss of Brain Aerobic Glycolysis in Normal Human Aging.
AB  - The normal aging human brain experiences global decreases in metabolism, but
      whether this affects the topography of brain metabolism is unknown. Here we
      describe PET-based measurements of brain glucose uptake, oxygen utilization, and
      blood flow in cognitively normal adults from 20 to 82 years of age. Age-related
      decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of
      brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose
      uptake, oxygen utilization, and blood flow remain largely stable with age, brain
      AG topography changes significantly. Brain regions with high AG in young adults
      show the greatest change, as do regions with prolonged developmental
      transcriptional features (i.e., neoteny). The normal aging human brain thus
      undergoes characteristic metabolic changes, largely driven by global loss and
      topographic changes in brain AG.

PMID- 28768175
TI  - Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake.
AB  - Proper brain function requires a substantial energy supply, up to 20% of whole
      body energy in humans, and brain activation produces large dynamic variations in
      energy demand. While local increases in cerebral blood flow are well known, the
      cellular responses to energy demand are controversial. During brain excitation,
      glycolysis of glucose to lactate temporarily exceeds the rate of mitochondrial
      fuel oxidation; although the increased energy demand occurs mainly within
      neurons, some have suggested this glycolysis occurs mainly in astrocytes, which
      then shuttle lactate to neurons as their primary fuel. Using metabolic biosensors
      in acute hippocampal slices and brains of awake mice, we find that neuronal
      metabolic responses to stimulation do not depend on astrocytic stimulation by
      glutamate release, nor do they require neuronal uptake of lactate; instead they
      reflect increased direct glucose consumption by neurons. Neuronal glycolysis
      temporarily outstrips oxidative metabolism, and provides a rapid response to
      increased energy demand.

PMID- 28768176
TI  - A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding.
AB  - Beige adipocytes can interconvert between white and brown-like states and switch
      between energy storage versus expenditure. Here we report that beige adipocyte
      plasticity is important for feeding-associated changes in energy expenditure and
      is coordinated by the hypothalamus and the phosphatase TCPTP. A fasting-induced
      and glucocorticoid-mediated induction of TCPTP, inhibited insulin signaling in
      AgRP/NPY neurons, repressed the browning of white fat and decreased energy
      expenditure. Conversely feeding reduced hypothalamic TCPTP, to increase AgRP/NPY
      neuronal insulin signaling, white adipose tissue browning and energy expenditure.
      The feeding-induced repression of hypothalamic TCPTP was defective in obesity.
      Mice lacking TCPTP in AgRP/NPY neurons were resistant to diet-induced obesity and
      had increased beige fat activity and energy expenditure. The deletion of
      hypothalamic TCPTP in obesity restored feeding-induced browning and increased
      energy expenditure to promote weight loss. Our studies define a hypothalamic
      switch that coordinates energy expenditure with feeding for the maintenance of
      energy balance.

PMID- 28768177
TI  - Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma
      Triglycerides in Mice and Humans: A Bedside to Bench Investigation.
AB  - Inhibiting lipogenesis prevents hepatic steatosis in rodents with insulin
      resistance. To determine if reducing lipogenesis functions similarly in humans,
      we developed MK-4074, a liver-specific inhibitor of acetyl-CoA carboxylase (ACC1)
      and (ACC2), enzymes that produce malonyl-CoA for fatty acid synthesis. MK-4074
      administered to subjects with hepatic steatosis for 1 month lowered lipogenesis,
      increased ketones, and reduced liver triglycerides by 36%. Unexpectedly, MK-4074
      increased plasma triglycerides by 200%. To further investigate, mice that lack
      ACC1 and ACC2 in hepatocytes (ACC dLKO) were generated. Deletion of ACCs
      decreased polyunsaturated fatty acid (PUFA) concentrations in liver due to
      reduced malonyl-CoA, which is required for elongation of essential fatty acids.
      PUFA deficiency induced SREBP-1c, which increased GPAT1 expression and VLDL
      secretion. PUFA supplementation or siRNA-mediated knockdown of GPAT1 normalized
      plasma triglycerides. Thus, inhibiting lipogenesis in humans reduced hepatic
      steatosis, but inhibiting ACC resulted in hypertriglyceridemia due to activation
      of SREBP-1c and increased VLDL secretion.

PMID- 28768179
TI  - mTORC1 Regulates Mitochondrial Integrated Stress Response and Mitochondrial
      Myopathy Progression.
AB  - Mitochondrial dysfunction elicits various stress responses in different model
      systems, but how these responses relate to each other and contribute to
      mitochondrial disease has remained unclear. Mitochondrial myopathy (MM) is the
      most common manifestation of adult-onset mitochondrial disease and shows a
      multifaceted tissue-specific stress response: (1) transcriptional response,
      including metabolic cytokines FGF21 and GDF15; (2) remodeling of one-carbon
      metabolism; and (3) mitochondrial unfolded protein response. We show that these
      processes are part of one integrated mitochondrial stress response (ISRmt), which
      is controlled by mTORC1 in muscle. mTORC1 inhibition by rapamycin downregulated
      all components of ISRmt, improved all MM hallmarks, and reversed the progression
      of even late-stage MM, without inducing mitochondrial biogenesis. Our evidence
      suggests that (1) chronic upregulation of anabolic pathways contributes to MM
      progression, (2) long-term induction of ISRmt is not protective for muscle, and
      (3) rapamycin treatment trials should be considered for adult-type MM with raised
      FGF21.

PMID- 28768178
TI  - Triglyceride Synthesis by DGAT1 Protects Adipocytes from Lipid-Induced ER Stress
      during Lipolysis.
AB  - Triglyceride (TG) storage in adipose tissue provides the major reservoir for
      metabolic energy in mammals. During lipolysis, fatty acids (FAs) are hydrolyzed
      from adipocyte TG stores and transported to other tissues for fuel. For unclear
      reasons, a large portion of hydrolyzed FAs in adipocytes is re-esterified to TGs
      in a "futile," ATP-consuming, energy dissipating cycle. Here we show that FA re
      esterification during adipocyte lipolysis is mediated by DGAT1, an ER-localized
      DGAT enzyme. Surprisingly, this re-esterification cycle does not preserve TG mass
      but instead functions to protect the ER from lipotoxic stress and related
      consequences, such as adipose tissue inflammation. Our data reveal an important
      role for DGAT activity and TG synthesis generally in averting ER stress and
      lipotoxicity, with specifically DGAT1 performing this function during stimulated
      lipolysis in adipocytes.

PMID- 28768180
TI  - Increased Total mtDNA Copy Number Cures Male Infertility Despite Unaltered mtDNA
      Mutation Load.
AB  - Mutations of mtDNA cause mitochondrial diseases and are implicated in age
      associated diseases and aging. Pathogenic mtDNA mutations are often present in a
      fraction of all mtDNA copies, and it has been widely debated whether the
      proportion of mutant genomes or the absolute number of wild-type molecules
      determines if oxidative phosphorylation (OXPHOS) will be impaired. Here, we have
      studied the male infertility phenotype of mtDNA mutator mice and demonstrate that
      decreasing mtDNA copy number worsens mitochondrial aberrations of spermatocytes
      and spermatids in testes, whereas an increase in mtDNA copy number rescues the
      fertility phenotype and normalizes testes morphology as well as spermatocyte
      proteome changes. The restoration of testes function occurs in spite of unaltered
      total mtDNA mutation load. We thus demonstrate that increased copy number of
      mtDNA can efficiently ameliorate a severe disease phenotype caused by mtDNA
      mutations, which has important implications for developing future strategies for
      treatment of mitochondrial dysfunction.

PMID- 28768182
TI  - DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs
      During Aging.

PMID- 28768181
TI  - Long-Term Cold Adaptation Does Not Require FGF21 or UCP1.
AB  - Brown adipose tissue (BAT)-dependent thermogenesis and its suggested augmenting
      hormone, FGF21, are potential therapeutic targets in current obesity and diabetes
      research. Here, we studied the role of UCP1 and FGF21 for metabolic homeostasis
      in the cold and dissected underlying molecular mechanisms using UCP1-FGF21 double
      knockout mice. We report that neither UCP1 nor FGF21, nor even compensatory
      increases of FGF21 serum levels in UCP1 knockout mice, are required for defense
      of body temperature or for maintenance of energy metabolism and body weight.
      Remarkably, cold-induced browning of inguinal white adipose tissue (iWAT) is
      FGF21 independent. Global RNA sequencing reveals major changes in response to
      UCP1- but not FGF21-ablation in BAT, iWAT, and muscle. Markers of mitochondrial
      failure and inflammation are observed in BAT, but in particular the enhanced
      metabolic reprogramming in iWAT supports the thermogenic role of UCP1 and
      excludes an important thermogenic role of endogenous FGF21 in normal cold
      acclimation.

PMID- 28768183
TI  - Learning and using knowledge about what other people do and don't know despite
      amnesia.
AB  - Successful communication requires keeping track of what other people do and do
      not know, and how this differs from our own knowledge. Here we ask how knowledge
      of what others know is stored in memory. We take a neuropsychological approach,
      comparing healthy adults to patients with severe declarative memory impairment
      (amnesia). We evaluate whether this memory impairment disrupts the ability to
      successfully acquire and use knowledge about what other people know when
      communicating with them. We tested participants in a referential communication
      task in which the participants described a series of abstract "tangram" images
      for a partner. Participants then repeated the task with the same partner or a new
      partner. Findings show that much like healthy individuals, individuals with
      amnesia successfully tailored their communicative language to the knowledge
      shared with their conversational partner-their common ground. They produced brief
      descriptions of the tangram images for the familiar partner and provided more
      descriptive, longer expressions for the new partner. These findings demonstrate
      remarkable sparing in amnesia of the acquisition and use of partner-specific
      knowledge that underlies common ground, and have important implications for
      understanding the memory systems that support conversational language.

PMID- 28768184
TI  - Cross-linked enzyme aggregates (CLEAs) and magnetic nanocomposite grafted CLEAs
      of GH26 endo-beta-1,4-mannanase: Improved activity, stability and reusability.
AB  - A comparative study on immobilization of recombinant endo-beta-1,4-mannanase
      (ManB-1601), using cross-linked aggregated form (MB-C) and novel chitosan
      magnetic nanocomposites of MB-C (MB-Mag-C) was carried out. FT-IR and Raman
      spectroscopy were used to confirm the surface modifications while, scanning
      electron and atomic force microscopy were performed to demonstrate the surface
      topology and magnetic nature of MB-C and MB-Mag-C. Among MB-C and MB-Mag-C, the
      former showed better activity and stability in broad range of pH, thermo
      stability and kinetic parameters while, the latter showed higher temperature
      optima and solvent stability. MB-C and MB-Mag-C when compared with free enzyme
      showed up to 73.2% higher activity (pH 4-9), up to 95.6% higher stability (pH 3
      10, 9h incubation at room temperature), up to 15 degrees C higher optimal
      temperature, higher stability (up to 83%) in the presence of solvents and up to
      1.62-fold higher deactivation energy (Ed). Immobilized enzymes were able to
      repeatedly hydrolyze locust bean gum till 12 cycles and generated predominantly
      di-, tri- and tetra- species of beta-manno-oligosaccharides.

PMID- 28768185
TI  - Preparation and characterization of hydroxypropyl chitosan modified with nisin.
AB  - Nisin had been grafted to hydroxypropyl chitosan (HPCS) using microbial
      transglutaminase (MTGase) as biocatalyst. HPCS was synthesized from chitosan and
      propylene oxide under alkali condition. The chemical structures of derivatives
      were characterized by FT-IR and 1H NMR spectroscopy. The process conditions were
      optimized from the aspects of the reaction time, the reaction temperature, the
      molar ratio of nisin to HPCS and the mass ratio of MTGase to HPCS. In this study,
      the results of moisture absorption and retention tests showed HPCS-nisin had
      moisture absorption and moisture retention abilities. In addition, in vitro
      antibacterial activity assessment, HPCS-nisin with the concentration of
      0.008mg/mL showed pronounced inhibitory effect against Gram-positive bacteria
      (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli).
      Furthermore, the methyl thiazolyl tetrazolium assay (MTT) was applied to evaluate
      the biocompatibility of HPCS-nisin, and the result indicated that HPCS-nisin with
      the degree of substitution (DS) of 0.18 displayed pronounced cell viability at
      500ppm in the range of certain toxicity. Therefore, the results suggest that HPCS
      nisin could be potential wound dressings for pharmaceutical applications.

PMID- 28768186
TI  - Enhanced catalytic stability of lipase immobilized on oxidized and disulfide-rich
      eggshell membrane for esters hydrolysis and transesterification.
AB  - Eggshell membrane (ESM) is an industrial waste that is available in abundance
      from food industry. Present study investigated the physicochemical properties of
      oxidized ESM and compared the efficiency of ESM and oxidized ESM as carrier for
      Burkholderia cepacia lipase (BCL) used in esters hydrolysis and
      transesterification. Following oxidation treatment, FTIR analysis and Ellman's
      assay showed amino acid cysteine in ESM was oxidized to form disulfide bond
      containing cystine. In addition, AFM analysis showed ESM which exhibited a highly
      porous filamentous structure appeared to be coalesce following oxidation
      treatment. Oxidized ESM also showed reduced porosity (38.67%) in comparison to
      native ESM (51.65%). BCL were successfully immobilized on oxidized ESM through
      carrier activation method (enzyme loading of 5.01mg protein/g oxidized ESM).
      These immobilized lipase demonstrated significantly (P<0.05) enhanced catalytic
      stability with close to 100% of initial hydrolysis (12.03+/-0.29mmol/min/g)
      activity; and more than 85% of its initial transesterification (7.83+/-0.05)
      activity for at least 10 consecutive runs. Enhanced catalytic stability of BCL
      immobilized on oxidized ESM might be due to stabilization of the protein
      structure in oxidized ESM by disulfide bonds which helped formation of a stable
      bonding with BCL.

PMID- 28768187
TI  - Interaction of Myoglobin colloids with BSA in solution: Insights into complex
      formation and elastic compliance.
AB  - This work focusses on the supramolecular complex formed between Myoglobin (Mb)
      and Bovine Serum Albumin (BSA) at colloids/solution interface at pH 4.0 and pH
      7.5. Electrostatic interactions between Mb as colloids and BSA solution (pH=7.5
      and 4.0) have been confirmed by Zeta potential that suggest that while Mb has a
      narrow interaction range, BSA has a wider interaction space. The organization of
      Mb colloids in BSA characterized using dilational rheological parameters show
      that the Mb colloids are elastic and the strong adsorbed water layers on the
      surface restrict the deformation, regulated by the viscoelastic surface layer.
      Stability of the complexes analyzed using UV-vis, Fluorescence and Circular
      dichroic spectroscopy indicate that there is a 1:1 interaction between Mb and BSA
      with a binding constant of about 105M-1. Quartz Crystal microbalance with
      dissipation has been used to evaluate the elastic compliance of the complexes of
      Mb colloids dispersed in very dilute BSA solution. The higher elastic compliance
      at pH=4.0 (than at pH=7.5) and the complex sizes correlate with changes in zeta
      potential suggesting that the mechanical properties of the protein in colloids
      are dependent on both the electrostatic interaction as well as the degree of
      hydration of the colloids.

PMID- 28768188
TI  - Blockage of Core Fucosylation Reduces Cell-Surface Expression of PD-1 and
      Promotes Anti-tumor Immune Responses of T Cells.
AB  - Programmed cell death 1 (PD-1) is highly expressed on exhausted T cells and
      inhibits T cell activation. Antibodies that block the interaction between PD-1
      and its ligand prevent this inhibitory signal and reverse T cell dysfunction,
      providing beneficial anti-tumor responses in a substantial number of patients.
      Mechanisms for the induction and maintenance of high PD-1 expression on exhausted
      T cells have not been fully understood. Utilizing a genome-wide loss-of-function
      screening method based on the CRISPR-Cas9 system, we identified genes involved in
      the core fucosylation pathway as positive regulators of cell-surface PD-1
      expression. Inhibition of Fut8, a core fucosyltransferase, by genetic ablation or
      pharmacologic inhibition reduced cell-surface expression of PD-1 and enhanced T
      cell activation, leading to more efficient tumor eradication. Taken together, our
      findings suggest that blocking core fucosylation of PD-1 can be a promising
      strategy for improving anti-tumor immune responses.

PMID- 28768189
TI  - Genetic-Metabolic Coupling for Targeted Metabolic Engineering.
AB  - Production of chemicals in microbes often employs potent biosynthetic enzymes,
      which can interact with the microbial native metabolism to affect cell fitness
      and product yield. However, production optimization largely relies on data
      collected from wild-type strains in the absence of metabolic perturbations, thus
      limiting their relevance to specific conditions. Here, we address this issue by
      coupling cell fitness to the production of thiamine diphosphate in Escherichia
      coli using a synthetic RNA biosensor. We use this strategy to interrogate a
      library of transposon mutants and elucidate the native gene network influencing
      both cell fitness and thiamine production. Ultimately, we identify effectors of
      the OxyR-Fur stress response that limit thiamine biosynthesis via alternative
      regulation of iron storage and Fe-S cluster inclusion in enzymes. This study
      presents a new approach for the reliable high-throughput identification of
      genetic targets of both known and unknown function that are directly relevant to
      a specific biosynthetic process.

PMID- 28768190
TI  - BMP4 Gene Therapy in Mature Mice Reduces BAT Activation but Protects from Obesity
      by Browning Subcutaneous Adipose Tissue.
AB  - We examined the effect of Bone Morphogenetic Protein 4 (BMP4) on energy
      expenditure in adult mature mice by targeting the liver with adeno-associated
      viral (AAV) BMP4 vectors to increase circulating levels. We verified the direct
      effect of BMP4 in inducing a brown oxidative phenotype in differentiating
      preadipocytes in vitro. AAV-BMP4-treated mice display marked browning of
      subcutaneous adipocytes, with increased mitochondria and Uncoupling Protein 1
      (UCP1). These mice are protected from obesity on a high-fat diet and have
      increased whole-body energy expenditure, improved insulin sensitivity, reduced
      liver fat, and reduced adipose tissue inflammation. On a control diet, they show
      unchanged body weight but improved insulin sensitivity. In contrast, AAV-BMP4
      treated mice showed beiging of BAT with reduced UCP1, increased lipids, and
      reduced hormone-sensitive lipase (HSL). Thus, BMP4 exerts different effects on
      WAT and BAT, but the overall effect is to enhance insulin sensitivity and whole
      body energy expenditure by browning subcutaneous adipose tissue.

PMID- 28768191
TI  - Intrinsic Autophagy Is Required for the Maintenance of Intestinal Stem Cells and
      for Irradiation-Induced Intestinal Regeneration.
AB  - Autophagy is a lysosomal degradation pathway with important roles in
      physiological homeostasis and disease. However, the role of autophagy in
      intestinal stem cells (ISCs) is unclear. Here, we show that intrinsic autophagy
      in ISCs is important for ISC homeostasis. Mice lacking autophagy protein 5 (ATG5)
      in intestinal epithelial cells (iECs) (Villin-Cre: Atg5fl/fl, hereafter
      Atg5DeltaIEC mice) or in all iECs except Paneth cells (Ah-Cre: Atg5fl/fl mice)
      had significantly fewer ISCs than did control mice and showed impaired ISC
      dependent intestinal recovery after irradiation. Crypt ISCs from Atg5DeltaIEC
      mice had significantly higher reactive oxygen species (ROS) levels than did those
      from control mice. A ROS-inducing reagent decreased the ISC number and impaired
      ISC regenerative capacity ex vivo, and treating Atg5DeltaIEC mice with an
      antioxidant rescued their defects. Our results show that intrinsic autophagy
      supports ISC maintenance by reducing excessive ROS. Optimizing autophagy may lead
      to autophagy-based therapies for intestinal injuries.

PMID- 28768192
TI  - Time-Restricted Feeding Shifts the Skin Circadian Clock and Alters UVB-Induced
      DNA Damage.
AB  - The epidermis is a highly regenerative barrier protecting organisms from
      environmental insults, including UV radiation, the main cause of skin cancer and
      skin aging. Here, we show that time-restricted feeding (RF) shifts the phase and
      alters the amplitude of the skin circadian clock and affects the expression of
      approximately 10% of the skin transcriptome. Furthermore, a large number of skin
      expressed genes are acutely regulated by food intake. Although the circadian
      clock is required for daily rhythms in DNA synthesis in epidermal progenitor
      cells, RF-induced shifts in clock phase do not alter the phase of DNA synthesis.
      However, RF alters both diurnal sensitivity to UVB-induced DNA damage and
      expression of the key DNA repair gene, Xpa. Together, our findings indicate
      regulation of skin function by time of feeding and emphasize a link between
      circadian rhythm, food intake, and skin health.

PMID- 28768193
TI  - Immunogenetic Profiling for Gastric Cancers Identifies Sulfated
      Glycosaminoglycans as Major and Functional B Cell Antigens in Human Malignancies.
AB  - Recent successes in tumor immunotherapies have highlighted the importance of
      tumor immunity. However, most of the work conducted to date has been on T cell
      immunity, while the role of B cell immunity in cancer remains more elusive. In
      this study, immunogenetic repertoire profiling for tumor-infiltrating B and T
      cells in gastric cancers was carried out to help reveal the architecture of B
      cell immunity in cancer. Humoral immunity in cancer was shown to involve
      oligoclonal expansions of tumor-specific and private B cell repertoires. We find
      that B cell repertoires in cancer are shaped by somatic hypermutation (SHM)
      either with or without positive selection biases, the latter of which tended to
      be auto-reactive. Importantly, we identified sulfated glycosaminoglycans (GAGs)
      as major functional B cell antigens among gastric tumors. Furthermore, natural
      anti-sulfated GAG antibodies discovered in gastric cancer tissues showed robust
      growth-suppressive functions against a wide variety of human malignancies of
      various organs.

PMID- 28768194
TI  - A Conserved Splicing Silencer Dynamically Regulates O-GlcNAc Transferase Intron
      Retention and O-GlcNAc Homeostasis.
AB  - Modification of nucleocytoplasmic proteins with O-GlcNAc regulates a wide variety
      of cellular processes and has been linked to human diseases. The enzymes O-GlcNAc
      transferase (OGT) and O-GlcNAcase (OGA) add and remove O-GlcNAc, but the
      mechanisms regulating their expression remain unclear. Here, we demonstrate that
      retention of the fourth intron of OGT is regulated in response to O-GlcNAc
      levels. We further define a conserved intronic splicing silencer (ISS) that is
      necessary for OGT intron retention. Deletion of the ISS in colon cancer cells
      leads to increases in OGT, but O-GlcNAc homeostasis is maintained by concomitant
      increases in OGA protein. However, the ISS-deleted cells are hypersensitive to
      OGA inhibition in culture and in soft agar. Moreover, growth of xenograft tumors
      from ISS-deleted cells is compromised in mice treated with an OGA inhibitor.
      Thus, ISS-mediated regulation of OGT intron retention is a key component in OGT
      expression and maintaining O-GlcNAc homeostasis.

PMID- 28768195
TI  - Attenuation of Synaptic Potentials in Dendritic Spines.
AB  - Dendritic spines receive the majority of excitatory inputs in many mammalian
      neurons, but their biophysical properties and exact role in dendritic integration
      are still unclear. Here, we study spine electrical properties in cultured
      hippocampal neurons using an improved genetically encoded voltage indicator
      (ArcLight) and two-photon glutamate uncaging. We find that back-propagating
      action potentials (bAPs) fully invade dendritic spines. However, uncaging
      excitatory post-synaptic potentials (uEPSPs) generated by glutamate photorelease,
      ranging from 4 to 27 mV in amplitude, are attenuated by up to 4-fold as they
      propagate to the parent dendrites. Finally, the simultaneous occurrence of bAPs
      and uEPSPs results in sublinear summation of membrane potential. Our results
      demonstrate that spines can behave as electric compartments, reducing the
      synaptic inputs injected into the cell, while receiving bAPs are unmodified. The
      attenuation of EPSPs by spines could have important repercussions for synaptic
      plasticity and dendritic integration.

PMID- 28768196
TI  - A Cooperative Mechanism Involving Ca2+-Permeable AMPA Receptors and Retrograde
      Activation of GABAB Receptors in Interpeduncular Nucleus Plasticity.
AB  - The medial habenula-interpeduncular nucleus (MHb-IPN) pathway, which connects the
      limbic forebrain to the midbrain, has recently been implicated in aversive
      behaviors. The MHb-IPN circuit is characterized by a unique topographical
      organization, an excitatory role of GABA, and a prominent co-release of
      neurotransmitters and neuropeptides. However, little is known about synaptic
      plasticity in this pathway. An application of a high-frequency stimulation
      resulted in a long-lasting potentiation of glutamate release in IPN neurons. Our
      experiments reveal that a Ca2+-permeable AMPA receptor (CPAR)-dependent release
      of GABA from IPN neurons and a retrograde activation of GABAB receptors on MHb
      terminals result in a long-lasting enhancement of glutamate release. Strikingly,
      adolescent IPN neurons lacked CPARs and exhibited an inability to undergo
      plasticity. In addition, fear conditioning suppressed an activity-dependent
      potentiation of MHb-IPN synapses, whereas fear extinction reversed this
      plasticity deficit, suggesting a role of the MHb-IPN synaptic plasticity in the
      regulation of aversive behaviors.

PMID- 28768197
TI  - Dual Effects of TARP gamma-2 on Glutamate Efficacy Can Account for AMPA Receptor
      Autoinactivation.
AB  - Fast excitatory transmission in the CNS is mediated mainly by AMPA-type glutamate
      receptors (AMPARs) associated with transmembrane AMPAR regulatory proteins
      (TARPs). At the high glutamate concentrations typically seen during synaptic
      transmission, TARPs slow receptor desensitization and enhance mean channel
      conductance. However, their influence on channels gated by low glutamate
      concentrations, as encountered during delayed transmitter clearance or synaptic
      spillover, is poorly understood. We report here that TARP gamma-2 reduces the
      ability of low glutamate concentrations to cause AMPAR desensitization and
      enhances channel gating at low glutamate occupancy. Simulations show that, by
      shifting the balance between AMPAR activation and desensitization, TARPs can
      markedly facilitate the transduction of spillover-mediated synaptic signaling.
      Furthermore, the dual effects of TARPs can account for biphasic steady-state
      glutamate concentration-response curves-a phenomenon termed "autoinactivation,"
      previously thought to reflect desensitization-mediated AMPAR/TARP dissociation.

PMID- 28768198
TI  - Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to
      Expression of Differentiation Markers after Injury.
AB  - Peripheral nerve regeneration after injury requires a broad program of
      transcriptional changes. We investigated the basis for the enhanced nerve
      regenerative capacity of the CAST/Ei mouse strain relative to C57BL/6 mice. RNA
      sequencing of dorsal root ganglia (DRG) showed a CAST/Ei-specific upregulation of
      Ascl1 after injury. Ascl1 overexpression in DRG neurons of C57BL/6 mice enhanced
      their neurite outgrowth. Ascl1 is regulated by miR-7048-3p, which is
      downregulated in CAST/Ei mice. Inhibition of miR-7048-3p enhances neurite
      outgrowth. Following injury, CAST/Ei neurons largely retained their mature
      neuronal profile as determined by single-cell RNA- seq, whereas the C57BL/6
      neurons acquired an immature profile. These findings suggest that one facet of
      the enhanced regenerative phenotype is preservation of neuronal identity in
      response to injury.

PMID- 28768199
TI  - Loss of Brap Results in Premature G1/S Phase Transition and Impeded Neural
      Progenitor Differentiation.
AB  - Cells initiate fate decisions during G1 phase by converting extracellular signals
      into distinctive cell cycle kinetics. The DNA replication timing is determined in
      G1 phase; lengthened G1 and hastened S phases correlate with increased neurogenic
      propensity of neural progenitor cells (NPCs), although the underlying molecular
      control remains elusive. Here, we report that proper G1 phase completion in NPCs
      requires Brap, a Ras-Erk signaling modulator with ubiquitin E3 ligase activity.
      We identified Skp2 and Skp2-associated SCF ubiquitin ligase as a key target of
      Brap-mediated polyubiquitination. Loss of Brap resulted in elevated Skp2, which
      increased p27Kip1 destruction, leading to G1 phase truncation and premature S
      phase entry. The aberrantly executed G1 in Brap-mutant NPCs, followed by hindered
      S phase progression and increased G2 phase arrest, which together prolonged the
      cell cycle, impeded neuronal differentiation and culminated in microcephaly.
      These findings demonstrate that neuronal differentiation is potentiated during G1
      phase by Brap-directed cascade of events in cell signaling and protein turnover.

PMID- 28768200
TI  - CFP1 Regulates Histone H3K4 Trimethylation and Developmental Potential in Mouse
      Oocytes.
AB  - Trimethylation of histone H3 at lysine-4 (H3K4me3) is associated with eukaryotic
      gene promoters and poises their transcriptional activation during development. To
      examine the in vivo function of H3K4me3 in the absence of DNA replication, we
      deleted CXXC finger protein 1 (CFP1), the DNA-binding subunit of the SETD1
      histone H3K4 methyltransferase, in developing oocytes. We find that CFP1 is
      required for H3K4me3 accumulation and the deposition of histone variants onto
      chromatin during oocyte maturation. Decreased H3K4me3 in oocytes caused global
      downregulation of transcription activity. Oocytes lacking CFP1 failed to complete
      maturation and were unable to gain developmental competence after fertilization,
      due to defects in cytoplasmic lattice formation, meiotic division, and maternal
      zygotic transition. Our study highlights the importance of H3K4me3 in continuous
      histone replacement for transcriptional regulation, chromatin remodeling, and
      normal developmental progression in a non-replicative system.

PMID- 28768201
TI  - Human TFIIH Kinase CDK7 Regulates Transcription-Associated Chromatin
      Modifications.
AB  - CDK7 phosphorylates the RNA polymerase II (pol II) C-terminal domain CTD and
      activates the P-TEFb-associated kinase CDK9, but its regulatory roles remain
      obscure. Here, using human CDK7 analog-sensitive (CDK7as) cells, we observed
      reduced capping enzyme recruitment, increased pol II promoter-proximal pausing,
      and defective termination at gene 3' ends upon CDK7 inhibition. We also noted
      that CDK7 regulates chromatin modifications downstream of transcription start
      sites. H3K4me3 spreading was restricted at gene 5' ends and H3K36me3 was
      displaced toward gene 3' ends in CDK7as cells. Mass spectrometry identified
      factors that bound TFIIH-phosphorylated versus P-TEFb-phosphorylated CTD (versus
      unmodified); capping enzymes and H3K4 methyltransferase complexes, SETD1A/B,
      selectively bound phosphorylated CTD, and the H3K36 methyltransferase SETD2
      specifically bound P-TEFb-phosphorylated CTD. Moreover, TFIIH-phosphorylated CTD
      stimulated SETD1A/B activity toward nucleosomes, revealing a mechanistic basis
      for CDK7 regulation of H3K4me3 spreading. Collectively, these results implicate a
      CDK7-dependent "CTD code" that regulates chromatin marks in addition to RNA
      processing and pol II pausing.

PMID- 28768203
TI  - Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4.
AB  - Low-pathogenicity avian influenza viruses (LPAIVs) have caused a global concern
      to public health since the first novel LPAIV H7N9 outbreak occurred. The receptor
      binding properties of the viral hemagglutinin are one key factor for efficient
      transmission and infection in humans. Recent evidence shows that H4 subtype
      viruses have been widely circulating in domestic poultry and human asymptomatic
      infections might have occurred. Here, we evaluated the receptor-binding
      properties of two representative isolates, avian H4N6 (containing Q226 and G228)
      and swine H4N6 (containing L226 and S228), and found that the avian isolate
      preferentially binds to avian receptors, whereas the swine isolate preferentially
      binds to human receptors. The Q226L and G228S substitutions are pivotal for the
      receptor-binding switch, which resulted in similar human receptor-binding
      features to the pandemic H2 and H3, implying that H4 has the potential to cause
      human infections. This early-warning study calls for future extensive
      surveillance.

PMID- 28768202
TI  - Dual RNA Processing Roles of Pat1b via Cytoplasmic Lsm1-7 and Nuclear Lsm2-8
      Complexes.
AB  - Pat1 RNA-binding proteins, enriched in processing bodies (P bodies), are key
      players in cytoplasmic 5' to 3' mRNA decay, activating decapping of mRNA in
      complex with the Lsm1-7 heptamer. Using co-immunoprecipitation and
      immunofluorescence approaches coupled with RNAi, we provide evidence for a
      nuclear complex of Pat1b with the Lsm2-8 heptamer, which binds to the
      spliceosomal U6 small nuclear RNA (snRNA). Furthermore, we establish the set of
      interactions connecting Pat1b/Lsm2-8/U6 snRNA/SART3 and additional U4/U6.U5 tri
      small nuclear ribonucleoprotein particle (tri-snRNP) components in Cajal bodies,
      the site of snRNP biogenesis. RNA sequencing following Pat1b depletion revealed
      the preferential upregulation of mRNAs normally found in P bodies and enriched in
      3' UTR AU-rich elements. Changes in >180 alternative splicing events were also
      observed, characterized by skipping of regulated exons with weak donor sites. Our
      data demonstrate the dual role of a decapping enhancer in pre-mRNA processing as
      well as in mRNA decay via distinct nuclear and cytoplasmic Lsm complexes.

PMID- 28768206
TI  - Multi-level Strategy for Identifying Proteasome-Catalyzed Spliced Epitopes
      Targeted by CD8+ T Cells during Bacterial Infection.
AB  - Proteasome-catalyzed peptide splicing (PCPS) generates peptides that are
      presented by MHC class I molecules, but because their identification is
      challenging, the immunological relevance of spliced peptides remains unclear.
      Here, we developed a reverse immunology-based multi-level approach to identify
      proteasome-generated spliced epitopes. Applying this strategy to a murine
      Listeria monocytogenes infection model, we identified two spliced epitopes within
      the secreted bacterial phospholipase PlcB that primed antigen-specific CD8+ T
      cells in L. monocytogenes-infected mice. While reacting to the spliced epitopes,
      these CD8+ T cells failed to recognize the non-spliced peptide parts in the
      context of their natural flanking sequences. Thus, we here show that PCPS expands
      the CD8+ T cell response against L. monocytogenes by exposing spliced epitopes on
      the cell surface. Moreover, our multi-level strategy opens up opportunities to
      systematically investigate proteins for spliced epitope candidates and thus
      strategies for immunotherapies or vaccine design.

PMID- 28768205
TI  - Impact of Alternative Splicing on the Human Proteome.
AB  - Alternative splicing is a critical determinant of genome complexity and, by
      implication, is assumed to engender proteomic diversity. This notion has not been
      experimentally tested in a targeted, quantitative manner. Here, we have developed
      an integrative approach to ask whether perturbations in mRNA splicing patterns
      alter the composition of the proteome. We integrate RNA sequencing (RNA-seq) (to
      comprehensively report intron retention, differential transcript usage, and gene
      expression) with a data-independent acquisition (DIA) method, SWATH-MS
      (sequential window acquisition of all theoretical spectra-mass spectrometry), to
      capture an unbiased, quantitative snapshot of the impact of constitutive and
      alternative splicing events on the proteome. Whereas intron retention is
      accompanied by decreased protein abundance, alterations in differential
      transcript usage and gene expression alter protein abundance proportionate to
      transcript levels. Our findings illustrate how RNA splicing links isoform
      expression in the human transcriptome with proteomic diversity and provides a
      foundation for studying perturbations associated with human diseases.

PMID- 28768207
TI  - Bm-muted, orthologous to mouse muted and encoding a subunit of the BLOC-1
      complex, is responsible for the otm translucent mutation of the silkworm Bombyx
      mori.
AB  - "Tanaka's mottled translucent" (otm) is a mutation of the silkworm Bombyx mori
      that exhibits translucent skin during larval stages. We performed positional
      cloning of the gene responsible for otm and mapped it to a 364-kb region on
      chromosome 5 that contains 22 hypothetical protein-coding genes. We performed RNA
      seq analysis of the epidermis and fat body of otm larvae and determined that the
      gene BGIBMGA002619 may be responsible for the otm mutation. BGIBMGA002619 encodes
      the biosynthesis of lysosome-related organelles complex 1 (BLOC-1) subunit 5,
      whose ortholog is responsible for the Muted mutant in mouse. Accordingly, we
      named this gene Bm-muted. We discovered that the expression of Bm-muted in the
      epidermis and fat body of otm mutants was dramatically suppressed compared with
      the wild type. We determined the nucleotide sequences of the full-length cDNA and
      genomic region corresponding to Bm-muted and found that a 538-bp long DNA
      sequence similar to B. mori transposon Organdy was inserted into the 3' end of
      the first intron of Bm-muted in two otm strains. The Bm-muted cDNA of otm mutants
      lacked exon 2, and accordingly generated a premature stop codon in exon 3. In
      addition, short interfering RNA (siRNA)-mediated knockdown of this gene caused
      localized partial translucency of larval skin. These data indicate that the
      mutation in Bm-muted caused the otm-mutant phenotype. We propose that the
      insertion of Organdy caused a splicing disorder in Bm-muted in the otm mutant,
      resulting in a null mutation of Bm-muted. This mutation is likely to cause
      deficiencies in urate granule formation in epidermal cells that result in
      translucent larval skin.

PMID- 28768208
TI  - Autobiographical memory deficits in patients with depression follow a temporal
      distribution.
AB  - Autobiographical memory deficits are known in depression. The temporal
      distribution thereof across periods of life has rarely been considered yet.
      Autobiographical memories for 5 life periods were investigated in 27 depressed in
      patients and compared to 31 matched healthy controls using the Bielefelder
      Autobiographisches Gedachtnis Inventar. Depressed patients reported significantly
      less details in memories dating from childhood to 30 years, correlating with
      severity of depression. Memories from childhood and recent periods were less
      positive in depressed patients. Thus, we found a distinct pattern of
      autobiographical memory deficits in depressed patients. Possible etiological
      factors, however, need further investigations.

PMID- 28768204
TI  - Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions
      during Mouse Early Gastrulation.
AB  - The mouse inner cell mass (ICM) segregates into the epiblast and primitive
      endoderm (PrE) lineages coincident with implantation of the embryo. The epiblast
      subsequently undergoes considerable expansion of cell numbers prior to
      gastrulation. To investigate underlying regulatory principles, we performed
      systematic single-cell RNA sequencing (seq) of conceptuses from E3.5 to E6.5. The
      epiblast shows reactivation and subsequent inactivation of the X chromosome, with
      Zfp57 expression associated with reactivation and inactivation together with
      other candidate regulators. At E6.5, the transition from epiblast to primitive
      streak is linked with decreased expression of polycomb subunits, suggesting a key
      regulatory role. Notably, our analyses suggest elevated transcriptional noise at
      E3.5 and within the non-committed epiblast at E6.5, coinciding with exit from
      pluripotency. By contrast, E6.5 primitive streak cells became highly synchronized
      and exhibit a shortened G1 cell-cycle phase, consistent with accelerated
      proliferation. Our study systematically charts transcriptional noise and uncovers
      molecular processes associated with early lineage decisions.

PMID- 28768209
TI  - Borderline personality disorder in men: A literature review and illustrative case
      vignettes.
AB  - The aim is to review the salient literature on borderline personality disorder
      (BPD) in men and link those findings with case vignettes. We provide a literature
      review and then report case examples of those who met DSM and clinical BPD
      criteria, and consider the extent to which the small male sub-set corresponded
      developmentally and phenomenologically with prototypic BPD in women. The review
      considered phenomenological, epidemiological, biological and developmental BPD
      factors, finding BPD men evidence elevated substance abuse, and 'externalising'
      patterns of behavior, antisocial personality traits, violent self-harm and
      interpersonal aggression, whereas women display more 'internalising' strategies.
      The five male vignettes enriched the literature review providing support for
      gender differences reported in our review. The literature and case vignette
      findings should assist clinicians in recognising that BPD in men may not be as
      rare as generally viewed, and which may reflect BPD being commonly viewed as
      weighted to women and being misdiagnosed as an antisocial personality disorder
      (ASPD) in men.

PMID- 28768210
TI  - Assessing renal function in patients receiving DOACs: Cockcroft-Gault versus
      estimated glomerular filtration rate.

PMID- 28768211
TI  - Assessing recovery of stream insects from pesticides using a two-patch
      metapopulation model.
AB  - Pesticides can exert lethal and sublethal effects on streams organisms. Field
      studies have shown that non-polluted upstream patches promote population recovery
      from such effects. Nevertheless, the dynamics and potential carryover effects on
      the upstream patch are largely unknown. We used a metapopulation model with 2
      patches to simulate lethal and sublethal effects on the downstream population of
      an insect with one generation per year, which was structured into early and late
      instars aquatic life stages, and an adult terrestrial life stage. We examined the
      implications for the recovery time of a range of scenarios covering different
      pesticide effect combinations, migration and exposure types. We found that
      recovery time responded most strongly to a reduction in reproduction in terms of
      the reduction of the intrinsic growth rate during the early instar aquatic life
      stage. For 60 of 96 scenarios with pesticide exposure in consecutive years, no
      recovery occurred within one year if the intrinsic growth rate was reduced by 50%
      or more. Without migration between patches (32 scenarios), the polluted
      downstream population went extinct in 5 of these scenarios. Migration lead
      overall to slightly faster recovery, albeit this was scenario dependent, but also
      to a carryover of the pesticide effect from the polluted downstream to the non
      polluted upstream patch (up to 25% reduction in the minimal population size). A
      sensitivity analysis revealed that recovery time was most sensitive to the
      parameters length of the intrinsic growth phase during early instar aquatic life
      stage and to migration mortality of the late instar aquatic larvae, and least
      sensitive to the adult emigration rate and timing of pesticide application. Our
      study highlights the important role of sublethal effects for population responses
      to pesticides and that migration buffers against effects, but also carries
      effects over to non-polluted patches.

PMID- 28768212
TI  - Effects of biosolids from a wastewater treatment plant receiving manufactured
      nanomaterials on Medicago truncatula and associated soil microbial communities at
      low nanomaterial concentrations.
AB  - Concern has grown regarding engineered nanomaterials (ENMs) entering agricultural
      soils through the application of biosolids and their possible effects on
      agroecosystems, even though the ENMs are extensively transformed. The effects of
      exposure to biosolids containing transformation products of these ENMs at low
      concentrations remain largely unexplored. We examined the responses of Medicago
      truncatula and its symbiotic rhizobia Sinorhizobium meliloti exposed to soil
      amended with biosolids from WWTP containing low added concentrations of ENMs (ENM
      Low), bulk/dissolved metals (bulk/dissolved Low), or no metal additions
      (control). We targeted adding approximately 5mg/kg of Ag and 50mg/kg of Zn, and
      Ti. Measured endpoints included M. truncatula growth, nodulation, changes in the
      expression of stress response genes, uptake of metals (Ag, Zn and Ti) into
      shoots, and quantification of S. meliloti populations and soil microbial
      communities. After 30days exposure, no effects on root or shoot biomass were
      observed in ENM Low and bulk/dissolved Low treatments, whereas both treatments
      had a larger average number of nodules (5.7 and 5.57, respectively) compared to
      controls (0.33). There were no significant differences in either total
      accumulated metal or metal concentrations in shoots among the treatments.
      Expression of five stress-related genes (metal tolerance protein (MTP), metal
      transporter (MTR), peroxidase (PEROX), NADPH oxidase (NADPH) and 1
      aminocyclopropane-1-carboxylate oxidase-like protein (ACC_Oxidase)) was
      significantly down-regulated in both bulk/dissolved Low and ENM Low treatments.
      However, a change in soil microbial community composition and a significant
      increase in total microbial biomass were observed in ENM Low relative to control.
      The ENM Low treatment had increased abundance of Gram-negative and anaerobic
      bacteria and reduced abundance of eukaryotes compared to control. The study
      demonstrated that although there were some subtle shifts in microbial community
      composition, plant health was minimally impacted by ENMs within the time frame
      and at the low exposure concentrations used in this study.

PMID- 28768213
TI  - Fractal dimension of large aggregates under different flocculation conditions.
AB  - The two-dimensional fractal dimension (Df) of large aggregates of kaolin
      (>540MUm) during the shear flocculation process for kaolin solution was
      investigated using non-intrusive in situ image-based acquisition system. Separate
      experiments were also carried out for three different sized sub-ranges of large
      aggregates (0.540-1.125mm; 1.125-1.750mm; 1.750-2.375mm). Digital images were
      taken at a frequency of 10Hz for 10s for each different pairs of gradients of
      velocity (Gf) of 20 and 60s-1 and flocculation times of 2; 3; 4; 5; 10; 20; 30;
      60; 120 and 180min. For the same conditions, particle size distribution (PSD) was
      also determined. Under the investigated conditions, the lowest Gf produced the
      greatest Df (1.69) at a flocculation time of 30min for the whole range of
      aggregates. Also, the evolution of the longest length of aggregate (l) and Df
      with time, showed that the dynamic steady-state was reached at different times
      for each shear rate and l ranges. However, Df varied for each size sub-range (ca.
      1.1 to 1.8). Finally, the behavior of the aggregate structure may be understood
      by the predominance of different aggregation mechanisms such as cluster-cluster
      for Gf of 60s-1 and particle-cluster for Gf of 20s-1.

PMID- 28768214
TI  - Estimation of disease burdens on preterm births and low birth weights
      attributable to maternal fine particulate matter exposure in Shanghai, China.
AB  - BACKGROUND: Studies have shown that maternal exposure to particulate matter
      <=2.5MUm in aerodynamic diameter (PM2.5) was associated with adverse birth
      outcomes such as preterm birth (PTB) and low birth weight (LBW). However, the
      burdens of PTB and LBW attributable to PM2.5 were rarely evaluated, especially in
      developing countries. OBJECTIVES: To estimate the burdens of PTBs and LBWs
      attributable to outdoor PM2.5 in Shanghai, China. METHODS: We collected annual
      average PM2.5 concentrations, concentration-response relationships between PM2.5
      exposure during pregnancy and PTBs and LBWs, rates of PTB and LBW, number of live
      births, and population sizes in grids of 10km*10km in Shanghai in 2013. Then,
      they were combined to estimate the odds ratios (ORs), relative risks (RRs),
      attributable fractions (AFs), and numbers of PTBs and LBWs associated with PM2.5
      exposure. RESULTS: The population-weighted annual-average concentration of PM2.5
      in Shanghai was 56.19MUg/m3 in 2013. According to the first-class limit of PM2.5
      (15MUg/m3) in the Ambient Air Quality Standards of China, the weighted RRs of
      PTBs or LBWs associated with PM2.5 in Shanghai were 1.49 [95% confidence interval
      (CI): 1.16-1.80] and 1.31 (95% CI: 1.04-1.67), respectively. There might be
      32.61% (95% CI: 13.93%-44.42%) or 4160 (95% CI: 1778-5667) PTBs and 23.36% (95%
      CI: 3.86%-40.02%) or 1882 (95% CI: 311-3224) LBWs attributable to PM2.5 exposure.
      The estimates varied appreciably among different districts of Shanghai.
      CONCLUSIONS: Our analysis suggested that outdoor PM2.5 air pollution might have
      led to considerable burdens of PTBs and LBWs in Shanghai, China.

PMID- 28768215
TI  - Assessment of the bioavailability, bioaccessibility and transfer of heavy metals
      in the soil-grain-human systems near a mining and smelting area in NW China.
AB  - Elucidating the transfer behaviour of heavy metals from soils to grains and
      ultimately to humans is of great significance for both human health risk
      assessment and pollution control. In this study, the bioavailability of heavy
      metals (Cd, Cu, Pb, Zn, Cr and Ni) in farmland soils and bioaccessibility in
      grains (spring wheat, maize and rice) were determined to elaborate transfer
      dynamics in the soil-grain-human systems near a mining and smelting area in the
      Dongdagou watershed, Baiyin district, Gansu province, NW China. The results
      showed that Cd, Cu, Pb and Zn concentrations in soils were elevated compared to
      background levels, while Cr and Ni concentrations were relatively low throughout
      the region. High levels of bioavailable soil Cd were found using both EDTA and
      CH3COOH extraction methods. Mean concentrations of Cd, Pb and Zn in spring wheat
      grains and the Cd and Cr concentrations in maize grains exceeded the relevant
      maximum levels for pollutants according to the Chinese national standards for
      food safety. Except for Ni (41.90%) and Pb (31.39%), heavy metal bioaccessibility
      was relatively low in grains, ranging from 10.80% (Cd) to 17.18% (Zn). CH3COOH
      extracted Cd, Pb and Ni, EDTA-extracted Zn, and total Cu in soils were the best
      indices for evaluation of uptake in grains (R2=0.54-0.91, p<0.001). Internal
      exposure doses of Cd and Ni in humans from spring wheat grain consumption was
      predicted by the linear correlations between bioaccessible and total metal
      concentrations (R2=0.61 and 0.67; p<0.001). The results from this study provide
      sufficient data and theoretical support for the use of these methods for local
      pollution prevention and control.

PMID- 28768216
TI  - A multi-omics based ecological analysis of coastal marine sediments from
      Gladstone, in Australia's Central Queensland, and Heron Island, a nearby fringing
      platform reef.
AB  - The impact of anthropogenic factors arising from point and non-point pollution
      sources at a multi commodity marine port and its surrounding ecosystems were
      studied using sediment samples collected from a number of onshore (Gladstone
      Harbour and Facing Island) and offshore (Heron Island and Fitzroy Reefs) sites in
      Australia's Central Queensland. Sediment samples were analyzed for trace metals,
      organic carbon, polycyclic aromatic hydrocarbons (PAH), emerging chemicals of
      concern (ECC) and sterols. Similarly, the biological and biochemical interaction
      between the reef and its environment was analyzed by the multi-omic tools of next
      generation sequencing characterization of the bacterial community and microbial
      community metabolic profiling. Overall, the trace elements were observed at the
      lower end of the Australian environmental guideline values at the offshore sites,
      while higher values were observed for the onshore locations Nickel and copper
      were observed above the high trigger value threshold at the onshore sites. The
      levels of PAH were below limits of detection across all sites. However, some of
      the ECC and sterols were observed at higher concentrations at both onshore and
      offshore locations, notably, the cholesterol family sterols and 17alpha
      ethynylestradiol. Multi-omic analyses also indicated possible thermal and photo
      irradiation stressors on the bacterial communities at all the tested sites. The
      observed populations of gamma-proteobacteria were found in combination with an
      increased pool of fatty acids that indicate fatty acid synthesis and utilisation
      of the intermediates of the shikimate pathways. This study demonstrates the value
      of applying a multi-omics approach for ecological assessments, in which a more
      detailed assessment of physical and chemical contaminants and their impact on the
      community bacterial biome is obtained.

PMID- 28768218
TI  - Monitoring long-term evolution of engineered barrier systems using magnets:
      Magnetic response.
AB  - Remote and non-destructive monitoring of the stability and performance of
      Engineered Barrier Systems for Geological Disposal Facility of is gaining
      considerable importance in establishing the safety cases for Higher Activity
      Wastes disposal. This study offers an innovative use of mineral magnetism for
      monitoring groundwater saturation of the barrier. Four mixtures of permanent
      magnets (Nd-Fe-B, coated and uncoated; SmCo and AlNiCo) and bentonite were
      reacted for 4, 8 and 12 months with mildly-saline, high-pH leachates,
      representing the fluids saturating a time-evolved engineered barrier. Coupled
      hysteresis and thermomagnetic analyses demonstrate how Nd-Fe-B feature a time
      dependent transition from square-like ferromagnetic to superparamagnetic loop via
      pot-bellied and wasp-waist loops, whereas SmCo and AlNiCo do not show so
      extensive corrosion-related variations of the intrinsic and extrinsic magnetic
      properties. This study allowed to identify magnetic materials suitable for
      shorter- (Nd-Fe-B) and longer-term (SmCo and AlNiCo) monitoring purposes.

PMID- 28768217
TI  - Randomised, open-label, phase II study comparing the efficacy and the safety of
      cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients
      with operable triple-negative or luminal B/HER2-negative breast cancer
      (GENEVIEVE).
AB  - BACKGROUND: The GENEVIEVE study compared the pathological complete response (pCR)
      rate (ypT0/is ypN0/+) in patients with operable human epidermal growth factor
      receptor 2 (HER2)-negative breast cancer (BC) treated with either cabazitaxel or
      paclitaxel. METHODS: GENEVIEVE was a prospective, multicentre, randomised, open
      label, phase II study comparing the efficacy and the safety of four 3-weekly
      cycles cabazitaxel versus 12 weeks of paclitaxel given as neoadjuvant treatment.
      Primary end-point was the pCR rate defined as the complete absence of invasive
      carcinoma on histological examination of the breast irrespective of lymph node
      involvement (ypT0/is, ypN0/+) after the taxane treatment. Patients could receive
      an anthracycline-based therapy thereafter. RESULTS: Overall, 333 patients were
      randomised and started treatment with 74.7% and 83.2% of patients completing
      treatment in the cabazitaxel and paclitaxel arms, respectively. Patients in
      cabazitaxel arm had a significantly lower pCR rate compared to the paclitaxel arm
      (1.2% versus 10.8%; p = 0.001). A total of 42 (25.3%) patients in the cabazitaxel
      arm and 17 (10.2%) in the paclitaxel arm had at least one serious adverse event
      (p < 0.001). Dose reductions were observed in 9.6% patients in the cabazitaxel
      arm compared to 11.4% in the paclitaxel arm (p = 0.721). Main reason for dose
      reductions was non-haematological toxicities in 3.0% versus 7.8% (p = 0.087),
      respectively. CONCLUSIONS: The GENEVIEVE study showed no short-term effect of
      cabazitaxel in triple-negative or luminal B/HER2-negative primary BC, while there
      seemed to be no differences in drug exposure and patient compliance between the
      two arms. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01779479.

PMID- 28768219
TI  - Removal of antimonate from wastewater by dissimilatory bacterial reduction: Role
      of the coexisting sulfate.
AB  - The priority pollutant antimony (Sb) exists primarily as Sb(V) and Sb(III) in
      natural waters, and Sb(III) is generally with greater mobility and toxicity than
      Sb(V). The bio-reduction of Sb(V) would not become a meaningful Sb-removal
      process unless the accumulation of produced dissolved Sb(III) could be
      controlled. Here, we examined the dissimilatory antimonate bio-reduction with or
      without the coexistence of sulfate using Sb-acclimated biomass. Results
      demonstrated that 0.8mM Sb(V) was almost completely bio-reduced within 20h along
      with 48.6% Sb(III) recovery. Kinetic parameters qmax and Ks calculated were
      0.54mg-Sb mg-DW-1h-1 and 41.96mgL-1, respectively. When the concentrations of
      coexisting sulfate were 0.8mM, 1.6mM, and 4mM, the reduction of 0.8mM Sb(V) was
      accomplished within 17, 9, and 5h, respectively, along with no final Sb(III)
      recovery. Also, the bio-reduction of sulfate occurred synchronously. The
      precipitated Sb2O3 and Sb2S3 were characterized by scanning electron microscopy
      coupled with energy dispersive spectrometer, X-ray diffraction, and X-ray
      photoelectron spectroscopy. Compared with bacterial compositions of the seed
      sludge obtained from anaerobic digestion tank in a wastewater treatment plant,
      new genera of Pseudomonas and Geobacter emerged with large proportions in both Sb
      fed and Sb-sulfate-fed sludge, and a small portion of sulfate reduction bacteria
      emerged only in Sb-sulfate-fed culture.

PMID- 28768220
TI  - Stable solidification of silica-based ammonium molybdophosphate by allophane:
      Application to treatment of radioactive cesium in secondary solid wastes
      generated from fukushima.
AB  - Silica-based ammonium molybdophosphate (AMP/SiO2) is an absorbent material that
      can effectively remove Cs from radioactive-contaminated wastewater (RCW)
      generated by Fukushima nuclide accident. Pressing/sintering method was used for
      final disposal of secondary waste (spent absorbent) to achieve the volume
      reduction of AMP-Cs/SiO2 (AMP/SiO2 saturation adsorption of Cs) and stable
      solidification of Cs by adding natural allophane. The structure of AMP-Cs
      completely collapsed at approximately 700 degrees C, and most Mo and P species in
      AMP sublimed. The optimal sintering temperature was estimated as 900 degrees C.
      The stable crystalline phase of Cs4Al4Si20O48 was recrystallized by the reaction
      of Cs2O, Al2O3, and SiO2, and the immobilization ratio of Cs was approximately
      100%. The leachability of Cs from the sintered product in distilled water was
      approximately 0.41%. The high immobilization and low leachability of Cs were
      attributed to the excellent solidification properties of the sintered products of
      AMP-Cs/SiO2-allophane.

PMID- 28768221
TI  - Assessment of the photocatalytic transformation of pyridinium-based ionic liquids
      in water.
AB  - We studied some ionic liquids (ILs) belonging to the pyridinium class under
      photocatalytic treatment. In particularly, we analysed how the length of the
      alkyl chain, the kind of inorganic ion and the type of substituents could
      influence the disappearance rate, the mineralization extent, the acute toxicity
      and the transformation mechanism. For such, we selected some pyridinium
      derivatives with different alkyl chain but the same anion, namely
      tetrafluoroborate (1-ethylpyridinium, 1-butylpyridinium, 1-hexylpyridinium), with
      two alkyl substituents (4-methyl-1-butylpyridinium) and with a different
      substituent (1-cyanopropylpyridinium). Then, on a selected IL (1
      butylpyridinium), we evaluate the role of different inorganic anions (bromine and
      chlorine). The results show that irrespective to the alkyl chain or the number of
      substituents, the transformation involved an attack to the alkyl chain, proceeded
      through the formation of harmless compounds and the mineralization was easily
      achieved within 4h. Nitrogen was mainly released as ammonium ion. When
      introducing a cyano group, the extent of nitrate ions and the number of possible
      transformation route increased. Conversely, the type of inorganic ion deeply
      affected the transformation pathways and the extent of mineralization. Actually,
      in the presence of bromide as anion, IL was only partially mineralized and the
      formation of highly persistent transformation products occurred.

PMID- 28768222
TI  - Metal leachability from coal combustion residuals under different pHs and
      liquid/solid ratios.
AB  - Coal combustion residuals (CCRs) contain variable amounts of trace metals, which
      can negatively impact the environment. We analyzed metal concentrations and
      leachability of CCRs from seven coal-fired power plants from Florida. The purpose
      of this study was to characterize and assess metal leachability in representative
      CCRs samples from coal-fired power plants, including As, Ba, Cd, Cr, Pb, and Se.
      The specific objectives were to: (1) measure metal leachability under different
      pH conditions and liquid-to-solid ratios using USEPA Leaching Environmental
      Assessment Framework (LEAF) Methods 1313 and 1316, and (2) compare their
      leachability with those obtained by the Synthetic Precipitation Leaching
      Procedure (SPLP). All metals excluding Cd showed amphoteric behavior, presenting
      higher concentrations at low and high pH using LEAF Method 1313. The highest Cd
      leaching was observed at pH 2-4 and decreased at pH>7. SPLP results were highly
      variable when compared to the LEAF data. All metals except Ba exceeded the
      Florida Groundwater Cleanup Target Levels at all pH levels, however, metal
      leaching was low at typical soil pH of 4-9. Metal concentrations in fly ash
      decreased in most cases with increasing LS ratio. Therefore, due to potential
      leaching of some metals, evaluation is needed before beneficial use of CCRs.

PMID- 28768223
TI  - Predicting PM10 concentration in Seoul metropolitan subway stations using
      artificial neural network (ANN).
AB  - The indoor air quality of subway systems can significantly affect the health of
      passengers since these systems are widely used for short-distance transit in
      metropolitan urban areas in many countries. The particles generated by abrasion
      during subway operations and the vehicle-emitted pollutants flowing in from the
      street in particular affect the air quality in underground subway stations. Thus
      the continuous monitoring of particulate matter (PM) in underground station is
      important to evaluate the exposure level of PM to passengers. However, it is
      difficult to obtain indoor PM data because the measurement systems are expensive
      and difficult to install and operate for significant periods of time in spaces
      crowded with people. In this study, we predicted the indoor PM concentration
      using the information of outdoor PM, the number of subway trains running, and
      information on ventilation operation by the artificial neural network (ANN)
      model. As well, we investigated the relationship between ANN's performance and
      the depth of underground subway station. ANN model showed a high correlation
      between the predicted and actual measured values and it was able to predict
      67~80% of PM at 6 subway station. In addition, we found that platform shape and
      depth influenced the model performance.

PMID- 28768224
TI  - IgG4-related hypertrophic pachymeningitis of the spine with MPO-ANCA
      seropositivity.
AB  - IgG4-related disease is an immune-mediated fibro-inflammatory condition that
      affects multiple organ systems. When the pachymeninges are involved, it is termed
      IgG4-related hypertrophic pachymeningitis (IgG4-RHP). We present a 79-year-old
      woman with back pain found to have IgG4-RHP localized exclusively in the spine
      who was also seropositive for myeloperoxidase anti-neutrophil cytoplasmic
      antibodies (MPO-ANCA). This case is the first known report of IgG4-RHP in the
      spine with MPO-ANCA and adds to emerging evidence for potential disease overlap
      in the pathogenesis of hypertrophic pachymenigitis (HP). We believe that
      increased awareness of this disease will result in an early diagnosis and
      initiation of life changing treatment.

PMID- 28768225
TI  - Complex liver cysts in Autosomal Dominant Polycystic Kidney Disease.
AB  - PURPOSE: To determine prevalence of complex liver cysts in Autosomal Dominant
      Polycystic Kidney Disease (ADPKD). METHODS: Abdominal MRI in 186 ADPKD subjects
      were evaluated by two independent observers to determine prevalence of complex
      liver cysts. RESULTS: 23 (12%) of subjects, had at least 1 complex cyst. Only 8
      (4%) were reported to have a complex cyst prospectively, representing an under
      reporting rate of 65%. Median total cyst volume was 66-times greater for subjects
      with complex cysts compared to subjects without (p<0.0001). CONCLUSION: Complex
      hepatic cysts were observed in 12% of ADPKD cases, occurring more frequently in
      livers with extensive cystic involvement.

PMID- 28768226
TI  - You can be too thin (but not too tall): Social desirability bias in self-reports
      of weight and height.
AB  - Previous studies of survey data from the U.S. and other countries find that women
      tend to understate their body weight on average, while both men and women
      overstate their height on average. Social norms have been posited as one
      potential explanation for misreporting of weight and height, but lack of
      awareness of body weight has been suggested as an alternative explanation, and
      the evidence presented to date is inconclusive. This paper is the first to offer
      a theoretical model of self-reporting behavior for weight and height, in which
      individuals face a tradeoff between reporting an accurate weight (or height) and
      reporting a socially desirable weight (or height). The model generates testable
      implications that help us to determine whether self-reporting errors arise
      because of social desirability bias or instead reflect lack of awareness of body
      weight and/or other factors. Using data from the National Health and Nutrition
      Examination Survey (NHANES) from 1999 to 2010, we find that self-reports of
      weight offer robust evidence of social desirability bias. However, lack of
      awareness of weight may also contribute to self-reporting biases, and this factor
      appears to be more important within some demographic groups than others. Among
      both women and men, self-reports of height exhibit significant social
      desirability bias only among those of below-average height, and very few
      individuals underreport their height. Implied self-reports of BMI exhibit gender
      specific patterns similar to those observed for self-reporting of weight, and the
      inferred social norms for BMI (20.8 for women and 24.8 for men) are within the
      "normal" range established by public health institutions. Determining why
      individuals misreport their weight has important implications for survey design
      as well as for clinical practice. For example, our findings suggest that health
      care providers might take additional steps to increase self-awareness of body
      weight. The framework also helps to explain previous findings that the degree of
      self-reporting bias in weight is stronger in telephone surveys than it is in in
      person surveys.

PMID- 28768228
TI  - Preeclampsia is associated with increased ambulatory arterial stiffness index in
      type 1 diabetes mellitus.
AB  - INTRODUCTION: Treatment of mild to moderate hypertension might not benefit
      maternal or fetal outcome. This pessimistic point of view may have come about by
      using non-validated methods for measuring blood pressure in pregnancy combined
      with inadequate methodology for diagnosis, treatment, and monitoring effects.
      AIM: To determine the association between AASI in women with type 1 diabetes
      mellitus (T1DM) and preeclampsia, and to assess the ability of AASI to diagnose
      preeclampsia. MATERIAL AND METHODS: Repeated 24-h ambulatory blood pressure
      recordings were performed three times during pregnancy and once three months
      postpartum in 151 women with T1DM and 50 control women without diabetes.
      Circadian rhythm was evaluated as the night day ratio, night blood pressure
      divided by day blood pressure. RESULTS: Of the T1DM women, 33 developed
      preeclampsia, which was associated with AASI in the 3rd trimester (p<0.05). The
      best predictor of preeclampsia in T1DM was an AASI of 0.35. The diurnal blood
      pressure was significantly higher in all trimesters in women who later had
      preeclampsia. A flattened circadian rhythm was present in T1DM women with
      preeclampsia compared to women without preeclampsia (night-day ratio: systole 2nd
      trimester: 0.94+/-0.07 vs. 0.91+/-0.05, women with and without preeclampsia,
      respectively, p=0.015; diastole 2nd trimester: 0.89+/-0.07 vs. 0.85+/-0.07,
      p=0.003). AASI was higher during pregnancy compared to postpartum in women with
      T1DM (0.31+/-0.16, 0.31+/-0.16 and 0.33+/-0.18 vs. 0.25+/-0.17; 1st, 2nd and 3rd
      trimester vs. postpartum). CONCLUSION: Women with T1DM and preeclampsia
      demonstrate increased arterial stiffness and had early manifestations in the non
      dipping of blood pressure.

PMID- 28768229
TI  - Individual resilience as a strategy to counter employment barriers for people
      with epilepsy in Zimbabwe.
AB  - Understanding individual resilience helps to improve employment opportunities of
      people with epilepsy. This is significant because, in Zimbabwe, as in many other
      countries in the Global South, people with epilepsy encounter several barriers in
      a context of less-than-ideal public services. Despite this disadvantage, some
      people with epilepsy have better employment outcomes for reasons including level
      of seizure control, social background, employment support services, and
      individual resilience. This article reports on data from participants (n=8), who
      were part of a larger study (n=30) on employment experiences of people with
      epilepsy in Harare. The study used in-depth interviews with the participants, who
      were all service users and members of the Epilepsy Support Foundation (ESF) in
      Harare. The eight resilient participants comprised four males and four females
      aged between 26-48years, who were selected because, unlike the remaining 22
      participants, they had overcome chronic unemployment. Seven of the eight
      participants were employed, while one had recently become unemployed. Views of
      service providers (n=7) were sought on the experiences of people with epilepsy
      through a focus group discussion. The service providers included two health
      workers, three social service workers, and two disability advocacy workers. Data
      were analysed using NVivo, a computer-assisted qualitative data analysis package.
      The study found that participants experienced barriers, such as a lack of medical
      treatment, yet this was important for education and training, lack of finances
      for training, and negative attitudes at workplaces. Despite these barriers,
      participants had overcome chronic unemployment due to their individual resilience
      characterised by: (i) a 'fighting spirit', (ii) being their own advocates, and
      (iii) having a mastery over, and acceptance of, their epilepsy. The research
      concluded that, where people with epilepsy faced barriers, as in Zimbabwe,
      individual resilience acted as a strong coping mechanism that resulted in better
      employment outcomes. This suggested service providers should strengthen
      resilience-building initiatives and make them more accessible to people with
      epilepsy. However, this is only a coping mechanism that should not stop service
      providers and service users from advocating for government-provided employment
      services.

PMID- 28768230
TI  - Thermal-stress analysis of ceramic laminate veneer restorations with different
      incisal preparations using micro-computed tomography-based 3D finite element
      models.
AB  - Main objective of this study is to investigate the thermal behavior of ceramic
      laminate veneer restorations of the maxillary central incisor with different
      incisal preparations such as butt joint and palatinal chamfer using finite
      element method. In addition, it is also aimed to understand the effect of
      different thermal loads which simulates hot and cold liquid imbibing in the
      mouth. Three-dimensional solid models of the sound tooth and prepared veneer
      restorations were obtained using micro-computed tomography images. Each ceramic
      veneer restoration was made up of ceramic, luting resin cement and adhesive layer
      which were generated based on the scanned images using computer-aided design
      software. Our solid model also included the remaining dental tissues such as
      periodontal ligament and surrounding cortical and spongy bones. Time-dependent
      linear thermal analyses were carried out to compare temperature changes and
      stress distributions of the sound and restored tooth models. The liquid is
      firstly in contact with the crown area where the maximum stresses were obtained.
      For the restorations, stresses on palatinal surfaces were found larger than
      buccal surfaces. Through interior tissues, the effect of thermal load diminished
      and smaller stress distributions were obtained near pulp and root-dentin regions.
      We found that the palatinal chamfer restoration presents comparatively larger
      stresses than the butt joint preparation. In addition, cold thermal loading
      showed larger temperature changes and stress distributions than those of hot
      thermal loading independent from the restoration technique.

PMID- 28768231
TI  - Case report of successful partial splenectomy for a splenic abscess in a
      paediatric patient.
AB  - INTRODUCTION: Splenic abscess (SA) is a rare potentially fatal condition in the
      paediatric population. It is difficult to diagnose given its non-specific
      presentation. There are no current guidelines for management of SA in this
      population but splenic preservation is advantageous given the vital role the
      spleen plays in immunity. PRESENTATION OF CASE: We present a case of a 15-year
      old boy with a large splenic abscess. He underwent successful partial splenectomy
      with resolution of his symptoms thereafter. DISCUSSION: Standard surgical
      treatment for splenic abscess is antibiotics and drainage. Spleen-preserving
      options include percutaneous drainage, partial splenectomy, subtotal splenectomy
      and splenic auto-transplantation. Spleen-preserving techniques should be used
      where possible to achieve best outcome in clearing infection and to ensure the
      immunologic role of the spleen is not compromised. CONCLUSION: Splenic abscess is
      rare conditions seen in paediatric practice with high mortality and partial
      splenectomy can be a useful spleen-preserving technique in treating this
      condition.

PMID- 28768232
TI  - Phase transition analysis of V-shaped liquid crystal: Combined temperature
      dependent FTIR and density functional theory approach.
AB  - Temperature-dependent Fourier transform infrared spectroscopy (FTIR) combined
      with density functional theory (DFT) is employed to study the mechanism of phase
      transitions of V-shaped bent-core liquid crystal. Since it has a large number of
      flexible bonds, one-dimensional potential energy scan (PES) was performed on the
      flexible bonds and predicted the most stable conformer I. A detailed analysis of
      vibrational normal modes of conformer I have been done on the basis of potential
      energy distribution. The good agreement between the calculated spectrum of
      conformer I and observed FTIR spectrum at room temperature validates our
      theoretical structure model. Furthermore, the prominent changes observed in the
      stretching vibrational bands of CH3/CH2, CO, ring CC, ring CO, ring CH in-plane
      bending, and ring CH out-of-plane bending at Iso->nematic phase transition (at
      155 degrees C) have been illustrated. However, the minor changes in the spectral
      features observed for the other phase transitions might be due to the shape or
      bulkiness of molecules. Combined FTIR and PES study beautifully explained the
      dynamics of the molecules, molecular realignment, H-bonding, and conformational
      changes at the phase transitions.

PMID- 28768227
TI  - Variation in the provision and practice of implant-based breast reconstruction in
      the UK: Results from the iBRA national practice questionnaire.
AB  - INTRODUCTION: The introduction of biological and synthetic meshes has
      revolutionised the practice of implant-based breast reconstruction (IBBR) but
      evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction
      evAluation) study is a national trainee-led project that aims to explore the
      practice and outcomes of IBBR to inform the design of a future trial. We report
      the results of the iBRA National Practice Questionnaire (NPQ) which aimed to
      comprehensively describe the provision and practice of IBBR across the UK.
      METHODS: A questionnaire investigating local practice and service provision of
      IBBR developed by the iBRA Steering Group was completed by trainee and consultant
      leads at breast and plastic surgical units across the UK. Summary data for each
      survey item were calculated and variation between centres and overall provision
      of care examined. RESULTS: 81 units within 79 NHS-hospitals completed the
      questionnaire. Units offered a range of reconstructive techniques, with IBBR
      accounting for 70% (IQR:50-80%) of participating units' immediate procedures.
      Units on average were staffed by 2.5 breast surgeons (IQR:2.0-3.0) and 2.0
      plastic surgeons (IQR:1.0-3.0) performing 35 IBBR cases per year (IQR:20-50).
      Variation was demonstrated in the provision of novel different techniques for
      IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and
      in patient selection for these procedures. CONCLUSIONS: The iBRA-NPQ has
      demonstrated marked variation in the provision and practice of IBBR in the UK.
      The prospective audit phase of the iBRA study will determine the safety and
      effectiveness of different approaches to IBBR and allow evidence-based best
      practice to be explored.

PMID- 28768247
TI  - Tracking Cognitive Decline in Amnestic Mild Cognitive Impairment and Early-Stage
      Alzheimer Dementia: Mini-Mental State Examination versus Neuropsychological
      Battery.
AB  - BACKGROUND/AIMS: Although the Mini-Mental State Examination (MMSE), Clinical
      Dementia Rating-Sum of Boxes (CDR-SOB), and neuropsychological batteries are
      widely used for evaluating cognitive function, it remains elusive which
      instrument best reflects the longitudinal disease progression in amnestic mild
      cognitive impairment (aMCI) and probable Alzheimer disease (AD). We investigated
      whether changes in these three instruments over time correlate with loss of
      cortical gray matter volume (cGMV). METHODS: We retrospectively investigated 204
      patients (aMCI, n = 114; AD, n = 90) who had undergone MMSE, CDR-SOB, the
      dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D), and
      3-dimensional T1-weighted magnetic resonance images at least twice. We
      investigated the partial correlation between annual decline in test scores and
      percent change of cGMV. RESULTS: In aMCI patients, changes in the SNSB-D total
      score (r = 0.340, p < 0.001) and CDR-SOB (r = 0.222, p = 0.020), but not MMSE,
      showed a correlation with cGMV loss, with the SNSB-D total score showing the
      strongest correlation. In AD patients, decline in all three test scores
      correlated significantly with cGMV loss, with MMSE exhibiting the strongest
      correlation (r = 0.464, p < 0.001). CONCLUSION: In aMCI patients,
      neuropsychological battery, though time-consuming, was the most adequate tool in
      tracking disease progression. In AD patients, however, MMSE may be the most
      effective longitudinal monitoring tool when considering cost-effectiveness.

PMID- 28768233
TI  - Identification of transcriptome signature for myocardial reductive stress.
AB  - The nuclear factor erythroid 2 like 2 (Nfe2l2/Nrf2) is a master regulator of
      antioxidant gene transcription. We recently identified that constitutive
      activation of Nrf2 (CaNrf2) caused reductive stress (RS) in the myocardium. Here
      we investigate how chronic Nrf2 activation alters myocardial mRNA transcriptome
      in the hearts of CaNrf2 transgenic (TG-low and TG-high) mice using an unbiased
      integrated systems approach and next generation RNA sequencing followed by qRT
      PCR methods. A total of 246 and 1031 differentially expressed genes (DEGs) were
      identified in the heart of TGL and TGH in relation to NTG littermates at ~ 6
      months of age. Notably, the expression and validation of the transcripts were
      gene-dosage dependent and statistically significant. Ingenuity Pathway Analysis
      identified enriched biological processes and canonical pathways associated with
      myocardial RS in the CaNrf2-TG mice. In addition, an overrepresentation of
      xenobiotic metabolic signaling, glutathione-mediated detoxification, unfolded
      protein response, and protein ubiquitination was observed. Other, non-canonical
      signaling pathways identified include: eNOS, integrin-linked kinase,
      glucocorticoid receptor, PI3/AKT, actin cytoskeleton, cardiac hypertrophy, and
      the endoplasmic reticulum stress response. In conclusion, this mRNA profiling
      identified a "biosignature" for pro-reductive (TGL) and reductive stress (TGH)
      that can predict the onset, rate of progression, and clinical outcome of Nrf2
      dependent myocardial complications. We anticipate that this global sequencing
      analysis will illuminate the undesirable effect of chronic Nrf2 signaling leading
      to RS-mediated pathogenesis besides providing important guidance for the
      application of Nrf2 activation-based cytoprotective strategies.

PMID- 28768248
TI  - Clinical Outcomes of Dietary Replacement of Saturated Fatty Acids with
      Unsaturated Fat Sources in Adults with Overweight and Obesity: A Systematic
      Review and Meta-Analysis of Randomized Control Trials.
AB  - BACKGROUND: Obesity and dyslipidemia are frequently treated with dietary
      interventions before pharmacotherapy is given. Diets high in unsaturated fat have
      proven advantageous to disease treatment. AIMS: The purpose of this systematic
      review and meta-analysis was to assess the evidence of the effect of saturated
      fatty acids (SFA) replacement with unsaturated fatty acids (UFA) in metabolically
      healthy adults with overweight and obesity on markers of dyslipidemia and body
      composition. METHODS: Keyword search was performed in PubMed, CINAHL, and
      Cochrane Library for randomized controlled trials (RCTs) evaluating the effects
      of fatty acid substitution in adults with overweight and obesity. Meta-analysis
      was performed on interventions assessing lipoprotein levels and body composition.
      Publication bias was assessed by funnel plot inspection, Begg's, and Egger's
      test. RESULTS: Eight RCTs enrolling 663 participants were included in the review,
      with intervention durations between 4 and 28 weeks. Although nonsignificant (p =
      0.06), meta-analysis found UFA replacement to reduce total cholesterol
      concentrations by 10.68 mg/dL (95%CI -21.90 to 0.53). Reductions in low-density
      lipoprotein cholesterol and triglycerides were statistically nonsignificant.
      CONCLUSIONS: Due to null results and a small number of studies included, there is
      no strong evidence that replacement of SFA with UFA may benefit lipid profiles in
      this population.

PMID- 28768249
TI  - Paediatric Home Parenteral Nutrition in the Czech Republic and Its Development:
      Multicentre Retrospective Study 1995-2011.
AB  - BACKGROUND: Treatment quality and outcomes of paediatric home parenteral
      nutrition (HPN) program during its development in the Czech Republic. METHODS: A
      retrospective study of patients receiving HPN from May 1995 till June 2011.
      RESULTS: Sixty-six patients were treated in 8 centres. In 48 patients, long-term
      PN began in the first year of life and in 35 of them in the first month. Sixty
      children had gastrointestinal and 6 had non-gastrointestinal disease. In a
      majority of the patients, the Broviac catheter was used. Thirty-two (48.5%)
      patients were weaned from PN after 1-117 months, 21 (32.8%) continued on HPN
      after 7-183 months, and 13 (19.7%) patients died, all on PN. The mortality in
      patients with primary gastrointestinal disease was significantly lower than in
      patients with non-gastrointestinal disease. Thirty-one paediatric patients were
      receiving HPN for 14,480 catheter days in 2009-2010. Fourteen patients had 23
      Catheter Related Blood Stream Infections (CRBSI) episodes. The incidence of CRBSI
      in 2009-2010 was 1.58/1,000 catheter days. CONCLUSION: Submitted data showed that
      even in the absence of expert centres, patient care may achieve results
      comparable to countries with well-developed HPN program. A majority of Czech HPN
      patients are at present treated in specialized centres, following the most
      desirable pattern of care.

PMID- 28768250
TI  - The Ameliorating Effect of Lactobacillus gasseri OLL2716 on Functional Dyspepsia
      in Helicobacter pylori-Uninfected Individuals: A Randomized Controlled Study.
AB  - BACKGROUND/AIMS: Probiotics appear to improve Helicobacter pylori-associated
      dyspepsia via an inhibitory effect on H. pylori; however, uncertainty exists
      regarding their effects in H. pylori-uninfected individuals. We evaluated the
      efficacy of Lactobacillus gasseri OLL2716 (L. gasseri OLL2716) on H. pylori
      uninfected individuals with functional dyspepsia (FD). METHODS: A double-blind,
      parallel-group, placebo-controlled, randomized, controlled trial was performed.
      Participants were randomly assigned to ingest L. gasseri OLL2716-containing
      yogurt (L. gasseri OLL2716 group) or L. gasseri OLL2716-free yogurt (placebo
      group) for 12 weeks. Participants completed questionnaires that dealt with a
      global assessment as well as symptom severity. The per-protocol (PP) population
      was evaluated for efficacy in accordance with a plan prepared beforehand.
      RESULTS: Randomization was performed on 116 individuals; the PP population
      consisted of 106 individuals (mean age 42.8 +/- 9.0). The impressions regarding
      the overall effect on gastric symptoms were more positive in the L. gasseri
      OLL2716 group compared to that in the placebo group (statistical trend; p =
      0.073). The elimination rate for major FD symptoms was 17.3 and 35.3% in the
      placebo and L. gasseri OLL2716 groups respectively (p = 0.048). CONCLUSION: L.
      gasseri OLL2716 has beneficial effects on FD without H. pylori involvement.

PMID- 28768251
TI  - A Randomized Controlled Trial Examining the Effect of Acupressure on Agitation
      and Salivary Cortisol in Nursing Home Residents with Dementia.
AB  - BACKGROUND: Acupressure has been used to manage agitation in people with dementia
      because it is safe and inexpensive. However, its effect on agitation and at the
      biochemical level is uncertain. METHODS: This randomized controlled trial
      examined the effect of acupressure on agitation, as measured by the Cohen
      Mansfield Agitation Inventory (CMAI); and on salivary cortisol, as measured at
      baseline (T0) and in the 3rd (T1), 5th (T2), and 8th (T3) weeks. There were 119
      agitated residents with dementia randomized into 3 groups: acupressure (n = 39),
      sham (n = 41), and usual-care group (n = 39). RESULTS: A downward trend in
      agitation over time was noted in the acupressure group, which almost reached a
      level of significance in interaction effects between groups and time points (p =
      0.052). Post hoc pairwise tests in the acupressure group showed that acupressure
      significantly reduced agitation at T2 (mean difference -6.84, 95% CI -10.60, 
      3.08) compared to baseline. Significant interaction effects between groups and
      time points were observed on the level of salivary cortisol (p = 0.022).
      CONCLUSION: Acupressure is a multicomponent intervention that can reduce
      agitation. Acupoint activation may not be a significant component in reducing
      agitation, although this result may have been limited by the inadequate sample
      size. Acupressure is effective in reducing salivary cortisol in people with
      dementia.

PMID- 28768252
TI  - Amniotic Fluid Concentrations of Glial Fibrillary Acidic Protein Do Not Correlate
      with Prenatal Metrics in Fetuses with Myelomeningocele.
AB  - INTRODUCTION: We investigated the correlation of amniotic fluid (AF)
      concentrations of glial fibrillary acidic protein (GFAP) with prenatal features
      of myelomeningocele (MMC) and neurodevelopmental outcome after fetal MMC (fMMC)
      surgery. MATERIALS AND METHODS: AF was collected during fMMC surgery between
      December 2012 and November 2015. AF-GFAP concentration was determined by ELISA.
      Retrospective chart review identified the characteristics of the defect. Data
      regarding delivery and 1-year neurodevelopmental outcome was collected from The
      Children's Hospital of Philadelphia fMMC Registry. RESULTS: Eighty-two AF samples
      were collected from fMMC surgeries. Perinatal data were obtained from 77
      subjects, and 1-year follow-up data from 65 subjects. GFAP concentrations were
      significantly elevated in MMC compared to myeloschisis (24.1 +/- 2.9 and 10.3 +/-
      1.5 ng/mL; p < 0.0001). A larger percentage of subjects with myeloschisis defects
      delivered before their scheduled due date (myeloschisis 88.5%; MMC 55.0%; p =
      0.003) and delivered at an earlier mean gestational age (34.6 +/- 0.4 weeks, n =
      26) compared to those with MMC defects (35.2 +/- 0.4 weeks, n = 51) (p = 0.04).
      DISCUSSION: AF-GFAP levels differentiate between MMC and myeloschisis, and raise
      interesting questions regarding the clinical significance between the 2 types of
      defects.

PMID- 28768253
TI  - 7th European Federation for Primatology Meeting. 30e Colloque de la Societe
      Francophone de Primatologie Strasbourg, France, August 21-25, 2017: Abstracts.

PMID- 28768254
TI  - Intracorporeal versus Extracorporeal Anastomoses Following Laparoscopic Right
      Colectomy in Obese Patients: A Case-Matched Study.
AB  - BACKGROUND/AIMS: To compare short- and long-term outcomes of intracorporeal
      anastomosis (IA) versus extracorporeal anastomosis (EA) in obese (body mass index
      >30 kg/m2) patients. PATIENTS AND METHODS: Sixty-four consecutive obese patients
      who underwent laparoscopic (LPS) right colectomy with IA were matched with 64
      patients who underwent LPS right colectomy with EA. Intraoperative variables,
      short-term outcomes, readmission rates, and morbidity and mortality rates were
      analyzed along with long-term outcomes. RESULTS: Conversion to open surgery
      occurred in 4 patients in the IA group and 11 patients in the EA group (p =
      0.097). The overall 30-day morbidity rate was 29.6% in the IA and 32.8% in the EA
      (p = 0.70). No 30-day mortality occurred. Anastomotic leak occurred in 4.7% of
      patients in the IA group vs. 7.8% in the EA group (p = 0.71). In the IA group, an
      earlier recovery of bowel function was observed (p = 0.01). No differences were
      observed with respect to the length of stay and reoperation rate. No 30-day
      readmission occurred in the IA compared to 5 patients readmitted in the EA group
      (p = 0.058). A higher incidence of incisional hernia was observed in the EA group
      (p = 0.033). CONCLUSION: IA in obese patients is associated with similar short
      term outcomes, lower incidence of incisional hernias, and might possibly reduce
      the risk of hospital readmission.

PMID- 28768255
TI  - Acne Fulminans: Treatment Experience from 26 Patients.
AB  - : Background /Aim: Acne fulminans is a rare form of acne vulgaris with acute
      clinical deterioration including systemic signs. Etiopathogenesis and management
      remain largely unknown. Our aim is to assess the efficacy of a combined
      therapeutic regimen of systemic isotretinoin and prednisolone following the
      recent concepts of acne pathogenesis and drug kinetics. METHODS: A prospective
      case series was recruited over 15 years. Isotretinoin 0.5 mg/kg bw/d (0.25-0
      0.25) and prednisolone 30 mg/d (10-10-10) were administered concomitantly with
      prednisolone being tapered after that time. The overall efficacy was evaluated at
      month 1 and every month thereafter. Daily drug doses were split to reduce the
      risk for adverse effects. RESULTS: 26 patients (20 male, 77%) at a mean age of 19
      years and a history of acne vulgaris of 3.2 years presented acutely necrotic and
      ulcerating skin papules (100%), fever (45%), arthralgia (38.5%), leukocytosis
      (88.5%) and elevated erythrocyte sedimentation rate (100%). After one month of
      treatment resolution of systemic signs was achieved in all patients and a >50%
      skin lesion improvement in 17 patients (65%). CONCLUSION: The concomitant
      administration of isotretinoin (0.5 mg/kg bw/d, 0.25-0-0.25) and prednisolone 30
      mg/d (10-10-10) is able to resolve systemic signs and markedly improve skin
      lesions in 65% of the patients at one month.

PMID- 28768256
TI  - Estimation of FST and the Impact of de novo Mutation.
AB  - OBJECTIVES: Wright defined FST as a measure of genetic differentiation. Cockerham
      developed an estimator of FST based on binary indicators in an ANOVA framework.
      Here, we address 2 issues regarding the estimation of FST. First, we derive a new
      estimator of FST based on the ANOVA framework using the doubly truncated normal
      distribution as an approximation of the binomial distribution to estimate
      variances. Second, we consider the impact of de novo mutation on FST estimation.
      METHODS: We compare our estimator to Weir and Cockerham's estimator via computer
      simulation. We apply our estimator to whole genome sequence data from the 1000
      Genomes Project. We use chimpanzee whole genome sequence data to ascertain for
      ancestral polymorphisms. RESULTS: By simulation, our new estimator is less biased
      than Weir and Cockerham's estimator for comparison of two subpopulations and is
      systematically more precise. As determined empirically by ascertainment of
      ancestral polymorphisms and theoretically, the effect of de novo mutation on FST
      estimation with human whole genome sequence data is statistically negligible. The
      effect of down-sampling ancestral polymorphisms is also statistically negligible.
      CONCLUSIONS: These results improve and simplify the use and interpretation of FST
      in studies of population structure.

PMID- 28768257
TI  - Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini
      Review.
AB  - Advancements in the field of biomedicine, including the control of infectious
      diseases through antibiotics and vaccination practices and the prevention of
      chronic disorders, have led to reduced mortality, increased life expectancy and,
      as such, growth of the older population. Ageing is accompanied by profound
      morphological and physiological alterations. In particular, the immune system
      undergoes a complex series of remodeling/restructuring events, involving almost
      all compartments - both the innate and the adaptive system. This process is
      termed immunosenescence or immune dysregulation and, basically, includes 3
      events: a reduction in immune response, an increase in the inflammatory and
      oxidation background (inflammaging and oxi-inflammaging), and a production of
      autoantibodies. While there is an increase in autoimmunity in the elderly, this
      does not always translate into an increase in autoimmune diseases, which
      represent an important cause of morbidity and mortality and affect 5-10% of the
      world population. Each disease involves a specific age group. Generally speaking,
      most autoimmune diseases have a decreased peak age of onset, except for very few
      diseases such as giant cell arteritis and primary biliary cirrhosis, which are
      more prevalent among the elderly, or inflammatory bowel disease, which has 2
      peaks of onset, the first one in young subjects and the other in those older than
      60 years. Autoimmune disorders in the elderly have unique clinical presentations,
      and insidious and atypical symptoms may constitute a challenge for the physician.
      They are generally milder than in adults and can be controlled by a proper
      therapeutic treatment. However, despite advancements both in basic and clinical
      sciences, further studies and investigations are warranted and should be carried
      out in order to dissect the molecular framework induced by ageing.

PMID- 28768258
TI  - Septic Complications after Resection for Middle or Low Rectal Cancer: Role of Gut
      Barrier Function and Inflammatory Serum Markers.
AB  - BACKGROUND: The focus of this study was to understand the relationship between
      the failure of gut barrier function, inflammatory markers and septic
      complications after resection for extraperitoneal rectal cancer. METHODS: One
      hundred seven patients were enrolled into this prospective observational study
      and underwent open colorectal resection for extraperitoneal cancer. All patients
      underwent an assessment of intestinal permeability (L/M ratio), endotoxemia,
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), C-reactive protein (CRP) and
      elastase levels before surgery and on postoperative days 1, 3, and 7. RESULTS:
      Septic complications developed in 23.3% of patients. There were no significant
      differences in preoperative L/M ratio, endotoxine, CRP, interleukin-1 (IL-1), IL
      6, and elastase levels between septic and non-septic groups. All patients showed
      a significant increase in intestinal permeability, endotoxemia, IL-1, IL-6, CRP,
      and elastase on the first postoperative day. At postoperative day 7, the septic
      group continued to demonstrate an increase in intestinal permeability,
      endotoxemia and elastase and significant difference was observed between the 2
      groups (p < 0.05), whereas there was no significant difference in IL-1, IL-6, and
      CRP levels. CONCLUSION: The pattern of change in the postoperative period of
      intestinal permeability, systemic endotoxemia and elastase concentration is
      significantly higher in patients in whom sepsis develops, while the concentration
      of IL-1beta, IL-6, and CRP does not permit to distinguish infection from
      inflammation.

PMID- 28768259
TI  - Prospective, Controlled Study of Invasiveness and Post-Aggression Metabolism in
      Patients Undergoing Robotic-Assisted Radical Prostatectomy.
AB  - OBJECTIVES: To evaluate in a prospective, controlled, nonrandomized study the
      surgical stress and acute-phase systemic response in robotic-assisted
      laparoscopic prostatectomy (RALP) compared to open radical retro-pubic
      prostatectomy (ORRP) by measuring humoral mediators. METHODS: Forty consecutive
      patients undergoing either RALP or ORRP were prospectively included to assess the
      extent of systemic response. Blood samples were collected before surgery (T1), at
      the time of prostatectomy (T2), at the time of wound closure (T3), and 12 h (T4),
      24 h (T5), and 48 h (T6) after surgery, and assayed for interleukins (IL-6 and IL
      10), C-reactive protein (CRP), and hemoglobin. A 2-sided p < 0.05 was considered
      to indicate significance. RESULTS: Baseline levels of IL-6, IL-10, and CRP were
      comparable in both arms of the study. IL-6 and IL-10 increased in both groups
      during surgery and reached maximum levels at 12 and 24 h after surgery. The RALP
      and RRP groups differed significantly at T2 (p = 0.009), T3 (p = 0.046), T5 (p =
      0.05) and T6 (p = 0.0007) for IL-6, and at T3 (p = 0.05) and T4 (p = 0.05) for IL
      10. CRP levels differed significantly at 48 h postoperative (p = 0.0053). The
      maximum levels of all 3 mediators in the RALP group were significantly lower than
      those in the open surgery group. Patients in the RALP group experienced less pain
      from day 2 to 4 according to the Visual Analog Scale (p < 0.05). CONCLUSIONS: The
      study suggests that IL-6 and IL-10 are useful objective markers for surgical
      stress and that tissue trauma and activation of post-aggression metabolism seem
      to be less in RALP compared to ORRP.

PMID- 28768260
TI  - Vitrectomy, Inner Limiting Membrane Peel, and Gas Tamponade in the Management of
      Traumatic Paediatric Macular Holes: A Case Series of 13 Patients.
AB  - PURPOSE: To review the outcomes of pars plana vitrectomy, internal limiting
      membrane (ILM) peel, and gas tamponade in the management of traumatic paediatric
      macular holes. METHODS: Retrospective case series of children undergoing
      vitrectomy, ILM peel, and gas tamponade for traumatic macular hole between March
      2007 and July 2014. Main outcome measures were postoperative visual acuity at 3
      and 12 months, anatomic closure rate, and surgical complications. RESULTS:
      Anatomic macular hole closure was achieved in 12 (92.3%) of 13 cases. Mean
      preoperative logMAR visual acuity was 0.91 (95% CI 0.65-1.17) with improvement
      postoperatively to 0.54 (95% CI 0.43-0.64) at 3 months (p = 0.002) and 0.50 (95%
      CI 0.39-0.60) at 12 months (p = 0.002). There were no perioperative
      complications. CONCLUSION: Pars plana vitrectomy and ILM peel is an effective
      management option for paediatric macular holes.

PMID- 28768261
TI  - Prostatic Arterial Embolization Followed by Holmium Laser Enucleation of the
      Prostate as a Planned Combined Approach for Extremely Enlarged Benign Prostate
      Hyperplasia.
AB  - OBJECTIVE: This study was aimed at reporting the initial experience with
      prostatic arterial embolization (PAE) followed by holmium laser enucleation of
      the prostate (HoLEP) as a planned combined approach for extremely enlarged benign
      prostate hyperplasia (BPH), and retrospectively estimating the efficacy and
      safety of this novel technique. PATIENTS AND METHODS: Twenty-four BPH patients
      who underwent PAE and subsequent HoLEP were included. The PAE procedure was
      performed under local anesthesia at the supine position with polyvinyl alcohol
      spherical particles and gelatin sponge particles. HoLEP was performed 3 months
      after PAE by the "en-bloc" enucleation technique. Clinical data before and 6
      months after the procedure were analyzed. RESULTS: PAE and HoLEP were technically
      successful in all 24 patients. The mean prostate volume was 219 +/- 38 mL; the
      mean total operative time and enucleation time for HoLEP were 117.8 +/- 21.9 and
      83.5 +/- 15.4 min, respectively; and the mean resected prostate weight was 118.3
      +/- 20.7 g. No transurethral resection of the prostate syndrome was observed
      during and after HoLEP. The estimated blood loss during HoLEP was 72.1 +/- 33.7
      mL, and no case required transfusion. International Prostate Symptom Score and
      post void residual volume decreased significantly (24.1 +/- 2.84 vs. 13.5 +/-
      3.39, p < 0.001; 107.1 +/- 40.8 vs. 21.8 +/- 16.8, p < 0.001, respectively),
      maximal flow rate increased significantly (6.25 +/- 1.42 vs. 17.63 +/- 16.56, p <
      0.001), and prostatic specific antigen level also decreased after the procedure
      (9.29 +/- 2.28 vs. 4.99 +/- 1.35, p < 0.001). CONCLUSIONS: PAE followed by HoLEP
      as a planned combined approach can be performed safely, feasibly, and efficiently
      in patients with extremely enlarged BPH.

PMID- 28768262
TI  - Clinical Evaluation of Urine Prostatic Exosomal Protein in the Diagnosis of
      Chronic Prostatitis.
AB  - OBJECTIVE: To evaluate the clinical potential of urine prostatic exosomal protein
      (PSEP) as a diagnostic biomarker of chronic prostatitis (CP). Materials
      andmethods: Using an enzyme-linked immunosorbent assay kit, urine PSEP levels
      were detected in 103 control cases as well as 283 cases of CP, with 82 cases
      fulfilling the definition of the USA National Institutes of Health category II
      (NIH-II), 108 cases of NIH-IIIa and 93 cases of NIH-IIIb. The values of age, body
      mass index, prostate volume, serum prostatic specific antigen (PSA) urine PSEP
      levels, and seminal parameters were analyzed. RESULTS: The PSEP levels were
      significantly higher in patients of NIH-II (2.09 [2.35] ng/mL), NIH-IIIa (1.80
      [2.95] ng/mL) and NIH-IIIb (1.64 [2.48] ng/mL) compared to the value of 0.24
      (0.76) ng/mL in the controls. ROC identified a cutoff value of 1.387 ng/mL, with
      a sensitivity of 59.0% and specificity of 94.2%. The area under the ROC curve was
      0.833. PSEP levels positively correlated with serum PSA levels in the NIH-IIIb
      group, and with EPS WBC count in the NIH-IIIa group, and with semen WBC count in
      each CP subgroups but negatively correlated with sperm motility in both the NIH
      IIIa group and the NIH-IIIb group. CONCLUSION: Urine PSEP could be a potential
      biomarker for CP.

PMID- 28768263
TI  - Saline Enemas versus Glycerin Suppositories to Promote Enteral Feeding in
      Premature Infants: A Pilot Randomized Controlled Trial.
AB  - BACKGROUND: Meconium retention is associated with feeding intolerance. Trials
      using glycerol and Gastrografin to expedite the evacuation of meconium have
      failed to generate clinically valid results for efficacy and safety. OBJECTIVE:
      We assessed the feasibility of aggressive meconium evacuation with saline rectal
      washout (RW) in very-low-birth-weight infants to reduce the time it took them to
      reach full enteral feeds. METHODS: We conducted an open-label, pilot, randomized
      controlled trial (RCT) (birth weight stratified, i.e., to 750-999 g and 1,000
      1,500 g) of early aggressive meconium evacuation with twice-daily normal saline
      RW compared to conventional management with glycerin suppositories (GS), until
      full enteral feeds (110 mL/kg/day) were reached. Primary outcome was time to
      reach full enteral feeds. Safety, process, and secondary efficacy outcomes were
      also evaluated. RESULTS: Sixty-one infants were randomized, 28 to RW and 33 to
      GS. The process and feasibility outcomes were met. RW was found to be safe; none
      of the RW-randomized infants developed necrotizing enterocolitis (>= stage II) or
      complications secondary to RW. Evidence of efficacy was supported: in the 750-999
      g stratum (n = 15), the median time to full enteral feeds was shorter with RW
      (11.0 days, 95% CI: 10.4-11.6) than with GS (15.6 days, 95% CI: 13.0-18.2) by a
      reduction of 4.6 days (p = 0.027). In the 1,000-1,500 g stratum (n = 46), there
      was no evidence of benefit: RW 10.2 days (95% CI 8.3-12.1) and GS 10.1 days (95%
      CI 9.3-10.9, p = 0.304). CONCLUSION: Our protocol was feasible and an adequately
      powered RCT is required to confirm the findings of this trial.

PMID- 28768264
TI  - Pathological Concordance between Prostate Biopsies and Radical Prostatectomy
      Using Transperineal Sector Mapping Biopsies: Validation and Comparison with
      Transrectal Biopsies.
AB  - : Background/Aims/Objectives: Our aim was to evaluate the accuracy of systematic
      transperineal sector mapping biopsy (TPSMB) in predicting Gleason score (GS) at
      radical prostatectomy (RP), to compare its accuracy with standard transrectal
      ultrasound-guided biopsies (TRUS) and to establish the clinical impact of
      discordance between biopsies and RP on subsequent surgical management. METHODS:
      Two hundred fifty-five patients from 2008 to 2013 who underwent RP following
      TPSMB (n = 204) or TRUS (n = 51), were included in this retrospective multi
      institutional study. Concordance between biopsies and RPs GS was assessed both as
      percentages and with Cohen's Kappa coefficient. All mismatches between biopsies
      and RP were assessed for significance by 3 urologists using the Delphi method.
      RESULTS: No differences were present among the groups. Concordance between biopsy
      and RP GS was 75.49% for TPSMB and 64.70% for TRUS. Kappa coefficient was 0.42
      and 0.39 respectively. The Delphi method showed lower clinical impact of GS
      discordances for TPSMB with 7.8% of patients having significant change, thus
      being potentially more suitable for other treatment modalities, compared to TRUS
      (13.7%). CONCLUSIONS: TPSMB had a higher accuracy for predicting the GS grade at
      RP showing superior GS concordance compared with standard TRUS. TPSMB provides an
      effective technique for systematic prostate biopsy to evaluate overall prostate
      cancer GS.

PMID- 28768265
TI  - Prompt Response to Prednisone Predicts Benign Course in MuSK-MG.
AB  - BACKGROUND: The difficult course of patients with myasthenia gravis (MG) with
      anti-muscle-specific tyrosine kinase antibodies (MuSK) has been emphasized.
      However, no clear information is available on patients who have a benign course.
      METHODS: This study was aimed at comparing patients with favorable (minimal
      manifestations [MM] or better) and unfavorable outcomes to determine whether
      excellent response to corticosteroid (CS) treatment within 3 months (good
      response-3 months) has any predictive effect on the prognosis. RESULTS: Forty-six
      percent of 46 patients had a favorable outcome at year 3 and 54% at final follow
      up. The major finding of this study was its high predictive value with good
      response-3 months. Those with good response-3 months had significantly more
      favorable outcome as compared to those without at year 3. The positive predictive
      value of good response-3 months was high (89% at year 3 and 84% at final follow
      up). The negative predictive value diminished from 85% at year 3 to 67% at final
      follow-up due to increasing number of patients improving in the long run.
      Overall, 33% of the patients had a benign course with good response-3 months and
      no major exacerbations until the end of follow-up. CONCLUSIONS: Excellent
      response to CSs within 3 months appears to predict a favorable outcome in MuSK
      MG.

PMID- 28768266
TI  - Aerodynamic and Laryngeal Characteristics of Place-Dependent Voice Onset Time
      Differences.
AB  - OBJECTIVE: To investigate aerodynamic and laryngeal factors associated with place
      dependent voice onset time (VOT) differences. METHODS: The speech materials were
      /p?, t?, k?/, each produced 15 times by 10 adult English speakers in the carrier
      phrase "say __ again". The sound pressure level was targeted within a +/-3 dB
      range. Intraoral air pressure (Po) was obtained using a buccal-sulcus approach.
      VOT, Po, maximum Po declination rate (MPDR), duration of the laryngeal devoicing
      gesture (LDG), occlusion duration, and the duration of the Po drop to baseline
      (atmosphere) to the onset of voicing (PDOV) were determined for each stop.
      RESULTS: VOT was longer for the alveolar and velar stops compared to the bilabial
      stop. A constant LDG was observed for all stops regardless of place of
      articulation. Occlusion duration, however, was significantly shorter for the
      alveolar and velar stops compared to the bilabial stop. Aerodynamically, Po was
      greatest for the velar stop, intermediate for the alveolar stop, and smallest for
      the bilabial stop. MPDR index showed a slower rate of Po drop for the velar and
      alveolar stops compared with the bilabial stop. PDOV was found to be longer for
      /p/ than /t/ and /k/. CONCLUSION: Findings provide empirical evidence for the
      inter-related roles of Po, rate of Po change, and laryngeal factors in place
      dependent variations of VOT.

PMID- 28768267
TI  - Presence of Concomitant Systemic Cancer is Not Associated with Worse Functional
      Long-Term Outcome in Patients with Intracerebral Hemorrhage.
AB  - BACKGROUND: Data on clinical characteristics and outcome of patients with
      intracerebral hemorrhage (ICH) and concomitant systemic cancer disease are very
      limited. METHODS: Nine hundred and seventy three consecutive primary ICH patients
      were analyzed using our prospective institutional registry over a period of 9
      years (2006-2014). We compared clinical and radiological parameters as well as
      outcome - scored using the modified Rankin Scale (mRS) and analyzed in a
      dichotomized fashion as favorable outcome (mRS = 0-3) and unfavorable outcome
      (mRS = 4-6) - of ICH patients with and without cancer. Relevant imbalances in
      baseline clinical and radiological characteristics were adjusted using propensity
      score (PS) matching. RESULTS: Prevalence of systemic cancer among patients with
      ICH was 8.5% (83/973). ICH patients with cancer were older (77 [70-82] vs. 72 [63
      80] years; p = 0.002), had more often prior renal dysfunction (19/83 [22.9%]
      vs.107/890 [12.0%]; p = 0.005), and smaller hemorrhage volumes (10.1 [4.8-24.3]
      vs. 15.3 [5.4-42.9] mL; p = 0.017). After PS-matching there were no significant
      differences neither in mortality nor in functional outcome both at 3 months
      (mortality: 33/81 [40.7%] vs. 55/158 [34.8%]; p = 0.368; mRS = 0-3: 28/81 [34.6%]
      vs. 52/158 [32.9%]; p = 0.797) and 12 months (mortality: 39/78 [50.0%] vs. 70/150
      [46.7%]; p = 0.633; mRS = 0-3: 25/78 [32.1%] vs. 53/150 [35.3%]; p = 0.620) among
      patients with and without concomitant systemic cancer. ICH volume tended to be
      highest in patients with hematooncologic malignancy and smallest in urothelial
      cancer. CONCLUSIONS: Patients with ICH and concomitant systemic cancer on average
      are older; however, they show smaller ICH volumes compared to patients without
      cancer. Yet, mortality and functional outcome is not different in ICH patients
      with and without cancer. Thus, the clinical history or the de novo diagnosis of
      concomitant malignancies in ICH patients should not lead to unjustified treatment
      restrictions.

PMID- 28768268
TI  - Qualitative and Quantitative Analysis of Primary Neocortical Areas in Selected
      Mammals.
AB  - The present study focuses on the relationship between neocortical structures and
      functional aspects in three selected mammalian species. Our aim was to compare
      cortical layering and neuron density in the projection areas (somatomotor, M1;
      somatosensory, S1; auditory, A1; and visual, V1; each in a wider sense).
      Morphological and design-based stereological analysis was performed in the wild
      boar (Sus scrofa scrofa) as a representative terrestrial hoofed animal
      (artiodactyl) and the common dolphin (Delphinus delphis) as a highly derived
      related aquatic mammal (cetartiodactyl). For comparison, we included the human
      (Homo sapiens) as a well-documented anthropoid primate. In the cortex of many
      mammals, layer IV (inner granular layer) is the main target of specific
      thalamocortical inputs while layers III and V are the main origins of neocortical
      projections. Because the fourth layer is indistinct or mostly lacking in the
      primary neocortex of the wild boar and dolphins, respectively, we analyzed the
      adjacent layers III and V in these animals. In the human, all the three layers
      were investigated separately. The stereological data show comparatively low
      neuron densities in all areas of the wild boar and high cell counts in the human
      (as expected), particularly in the primary visual cortex. The common dolphin, in
      general, holds an intermediate position in terms of neuron density but exhibits
      higher values than the human in a few layers. With respect to the situation in
      the wild boar, stereological neuron counts in the dolphin are consistently
      higher, with a maximum in layer III of the visual cortex. The extended auditory
      neocortical field in dolphins and the hypertrophic auditory pathway indicate
      secondary neurobiological adaptations to their aquatic habitat during evolution.
      The wild boar, however, an omnivorous quadruped terrestrial mammal, shows
      striking specializations as to the sensorimotor neurobiology of the snout region.

PMID- 28768269
TI  - A Potential Role for the NOD1 Variant (rs6958571) in Gram-Positive Blood Stream
      Infection in ELBW Infants.
AB  - BACKGROUND: The genetic basis of sepsis susceptibility in preterm infants remains
      understudied. Herein, we investigated the nucleotide binding-oligomerization
      domain (NOD)-like receptor (NLR) family of immune receptors as putative loci for
      preterm sepsis susceptibility. OBJECTIVE: To determine whether single nucleotide
      polymorphisms (SNPs) in NLR genes are associated with blood stream infections
      (BSI) in premature infants. METHODS: An international cohort of infants with
      gestational age (GA) <35 weeks were genotyped for SNPs in the ATG16L1, CARD8,
      NLRP3, NOD2, and NOD1 genes. chi2 and logistic regression analyses were used to
      examine relationships between NLR variants and BSI. RESULTS: Among 764 infants,
      138 developed BSI, 113 had gram-positive bacterial (GPB) BSI, and 28 had gram
      negative bacterial (GNB) BSI. Infants with BSI had a lower birth weight and GA (p
      < 0.001), but did not differ in gender, race, or chorioamnionitis. NLR variants
      were not associated with GPB or GNB BSI in the entire cohort. The CC genotype of
      the NOD1 SNP (rs6958571) was associated with increased GPB BSI in extremely low
      birth weight (ELBW, birth weight <1,000 g) infants (OR = 3.3, 95% CI: 1.4-7.5, p
      = 0.003, n = 362) and in Caucasian infants (OR = 2.5, 95% CI: 1.2-5.4, p = 0.016,
      n = 535). Regression models adjusting for clinical variables identified ELBW
      status and the NOD1 CC genotype as risk factors for GPB BSI in Caucasian infants.
      CONCLUSIONS: In this study investigating relationships between NLR variants and
      sepsis in infants with GA <35 weeks, the NOD1 (rs6958571) SNP was associated with
      GPB BSI in Caucasian infants and ELBW infants. Replication of our results in an
      independent cohort would support a role for NLR variants in determining sepsis
      risk in ELBW infants.

PMID- 28768270
TI  - The Integrated Care of Asthma in Switzerland (INCAS) Study: Changes in Asthma
      Control and Perception of Health Care through Asthma Education.
AB  - BACKGROUND: Despite great efforts in establishing optimal asthma management,
      asthma may remain uncontrolled. To effectively manage chronic diseases, such as
      asthma, it is important to train patients in self-management skills. OBJECTIVES:
      The aim of this study was to assess the potential benefit of standardised asthma
      education in Switzerland for asthma control and patients' perception of received
      asthma care and of self-management support. METHODS: For this multicentre
      longitudinal controlled study, asthma patients were recruited in Switzerland. The
      Asthma Control Test (ACT) was used to assess asthma control. The Patient
      Assessment of Chronic Illness Care questionnaire (PACIC 5A) was applied to
      evaluate received health-care services and self-management support. Patients were
      offered the possibility to attend asthma education sessions conducted by the
      Swiss Lung League and Swiss Allergy Centre. After 1 year, attenders and non
      attenders completed the questionnaires again. Changes in ACT and PACIC 5A scores
      were analysed using dependent t tests. RESULTS: Overall, 223 patients with asthma
      were investigated (mean age 43 +/- 12 years, 38% male, 13% current smokers, 29%
      ex-smokers). Sixty-one (27%) patients attended education sessions. Both groups
      had improved asthma control at follow-up (attenders: t(56) = -3.2, r = 0.4
      [medium effect size], p = 0.002; non-attenders: t(141) = -2.6, r = 0.2 [small
      effect size], p = 0.010). Attenders improved in PACIC and 5A sum scores (t(50) = 
      3.6, r = 0.5 [medium effect size], p = 0.001). CONCLUSIONS: A comprehensive self
      management asthma education programme in Switzerland improved asthma control and
      patients' perception of received asthma care and of self-management support.
      Professionals should motivate patients to attend asthma education in order to
      become active partners in managing their disease.

PMID- 28768271
TI  - Long-Term Outcomes and Associated Risk Factors of Post-Hospitalization Dialysis
      Dependent Acute Kidney Injury Patients.
AB  - BACKGROUND/AIMS: Acute kidney injury requiring dialysis (AKI-D) is associated
      with poor outcomes. Centers for Medicare and Medicaid Services have reversed
      their clarification allowing AKI-D patients to be dialyzed at outpatient dialysis
      units. Data assessing long-term outcomes of AKI-D patients and their predictors
      is needed to adopt guidelines to ensure adequate management. We assessed long
      term outcomes and associated risk factors of AKI-D patients who survived 90 days
      post-hemodialysis (HD) initiation. METHODS: AKI-D patients surviving
      hospitalization and dialyzed at a specialized outpatient AKI dialysis unit
      between April 11, 2012 and December 25, 2013 were prospectively followed. Long
      term outcomes of AKI-D patients were obtained by a single provider through a
      telephone survey, and factors affecting their outcomes were statistically
      analyzed. RESULTS: Ninety-one out of 108 patients were reached for telephone
      survey. At baseline (90 days post-HD initiation), 52/91 patients were declared
      end-stage renal disease (ESRD; group 1) and 39/91 were dialysis-independent
      (group 2). At the end of an average follow up period of 859.7 days, 32/91 (35.2%)
      were dialysis-independent (3/52 from group 1 and 29/39 from group 2), with 28/91
      dead (25/52 from group 1 and 3/39 from group 2). After adjusting for demographics
      and comorbidities, baseline renal function, prior AKI, ESRD, and requirement for
      continuous renal replacement therapy were associated with poor outcomes.
      CONCLUSIONS: Sustaining long-term dialysis independence in AKI-D patients is
      significant. Baseline renal function, prior AKI, and hemodynamic changes during
      hospitalization are predictors of long-term outcomes. Meticulous follow up of AKI
      D patients in the outpatient dialysis facilities in their first 90 days post-HD
      initiation is crucial.

PMID- 28768273
TI  - Erratum.

PMID- 28768272
TI  - Comparison between Primary and Secondary Tracheoesophageal Puncture Prosthesis: A
      Systematic Review.
AB  - INTRODUCTION: Since the introduction of tracheoesophageal puncture (TEP) and
      placement of voice prosthesis, this has become the method of choice to achieve
      speech rehabilitation after total laryngectomy. OBJECTIVE: To compare the
      complications and success in speech rehabilitation of patients undergoing
      rehabilitation after primary and secondary TEP (TEP1 and TEP2) through a
      systematic review. METHODS: The literature survey included research in MedLine,
      Scielo, Lilacs, Cochrane and Websco until June 2016. RESULTS: The rate of leakage
      around the prosthesis was higher in TEP1 (22.5 vs. 6.9%, p = 0.03). There were
      higher rates of wound infection (9.1 vs. 3.9%) and tracheal stenosis (8.5 vs.
      4.5%) in the TEP1 group compared to TEP2, however with no statistical
      significance. The evaluation of speech quality was not possible due to the
      heterogeneity of the studies. CONCLUSION: There is a reduction in the risk of
      leakage around the prosthesis among TEP2 patients.

PMID- 28768274
TI  - PharmaForum.

PMID- 28768275
TI  - PharmaForum.

PMID- 28768276
TI  - PharmaForum.

PMID- 28768277
TI  - PharmaNews.

PMID- 28768278
TI  - PharmaNews.

PMID- 28768279
TI  - Meetings and Conferences.

PMID- 28768280
TI  - Chest Compressions during Sustained Inflations Improve Recovery When Compared to
      a 3:1 Compression:Ventilation Ratio during Cardiopulmonary Resuscitation in a
      Neonatal Porcine Model of Asphyxia.
AB  - BACKGROUND: Recently, sustained inflations (SI) during chest compression (CC)
      (CC+SI) have been suggested as an alternative to the current approach during
      neonatal resuscitation. No previous study compared CC+SI using CC rates of 90/min
      to the current 3:1 compression:ventilation ratio (C:V). OBJECTIVE: To determine
      whether CC+SI versus a 3:1 C:V reduces the time to the return of spontaneous
      circulation (ROSC) and improves hemodynamic recovery in newborn piglets with
      asphyxia-induced bradycardia. INTERVENTION AND MEASUREMENTS: Term newborn piglets
      were anesthetized, intubated, instrumented, and exposed to 45-min normocapnic
      hypoxia followed by asphyxia. Cardiopulmonary resuscitation (CPR) was initiated
      when the heart rate decreased to 25% of baseline. Piglets were randomized into 3
      groups: CC during SI at a rate of 90 CC/min (SI+CC 90, n = 8), a 3:1 C:V using 90
      CC and 30 inflations (3:1, n = 8), or a sham group (n = 6). Cardiac function,
      carotid blood flow, cerebral oxygenation, and respiratory parameters were
      continuously recorded throughout the experiment. RESULTS: CC+SI significantly
      reduced the median (IQR) time of ROSC, i.e., 34 s (28-156 s) versus 210 s (72-300
      s) in the 3:1 group (p = 0.048). CC+SI also significantly reduced the requirement
      for 100% oxygen, improved respiratory parameters, and resulted in a similar
      hemodynamic recovery. CONCLUSIONS: CC+SI during CPR significantly improved ROSC
      in a porcine model of neonatal resuscitation. This is of considerable clinical
      relevance because improved respiratory and hemodynamic parameters potentially
      minimize morbidity and mortality in newborn infants.

PMID- 28768281
TI  - beta-Sarcoglycan Deficiency Reduces Atherosclerotic Plaque Development in ApoE
      Null Mice.
AB  - BACKGROUND: Smooth muscle cells are important for atherosclerotic plaque
      stability. Their proper ability to communicate with the extracellular matrix is
      crucial for maintaining the correct tissue integrity. In this study, we have
      investigated the role of beta-sarcoglycan within the matrix-binding dystrophin
      glycoprotein complex in the development of atherosclerosis. RESULTS:
      Atherosclerotic plaque development was significantly reduced in ApoE-deficient
      mice lacking beta-sarcoglycan, and their plaques contained an increase in
      differentiated smooth muscle cells. ApoE-deficient mice lacking beta-sarcoglycan
      showed a reduction in ovarian adipose tissue and adipocyte size, while the total
      weight of the animals was not significantly different. Western blot analysis of
      adipose tissues showed a decreased activation of protein kinase B, while that of
      AMP-activated kinase was increased in mice lacking beta-sarcoglycan. Analysis of
      plasma in beta-sarcoglycan-deficient mice revealed reduced levels of leptin,
      adiponectin, insulin, cholesterol, and triglycerides but increased levels of IL
      6, IL-17, and TNF-alpha. CONCLUSIONS: Our results indicate that the dystrophin
      glycoprotein complex and beta-sarcoglycan can affect the atherosclerotic process.
      Furthermore, the results show the effects of beta-sarcoglycan deficiency on
      adipose tissue and lipid metabolism, which may also have contributed to the
      atherosclerotic plaque reduction.

PMID- 28768282
TI  - Increased Non-High-Density Lipoprotein Cholesterol in Children and Young Adults
      with Turner Syndrome Is Not Explained By BMI Alone.
AB  - BACKGROUND: Turner syndrome (TS) is associated with an increased risk of
      cardiovascular disease. Non-high-density lipoprotein cholesterol (non-HDL-C) is a
      convenient measure of atherogenicity (normal concentration <120 mg/dL) but has
      not been investigated in TS. We aim to evaluate non-HDL-C patterns in a cohort of
      pediatric and young adult females with TS. METHODS: A retrospective chart review
      was used to obtain demographics, body composition, genetic reports, and lipid
      profiles in females with TS. RESULTS: Lipid profiles were assessed in 158 females
      (mean age 13.6 years). Mean non-HDL-C was 118.9 mg/dL (+/-32.0); the prevalence
      of high non-HDL-C (>=144 mg/dL) was 17.7% (n = 28). In TS females aged 8-17 years
      (n = 46), the prevalence of high non-HDL-C was 23.9% (95% CI 11.1-36.7; n = 11)
      between 2011 and 2012, compared to 9.2% (95% CI 5.6-14.1) in females of the same
      age in the general population reported in the National Health and Nutrition
      Examination Survey (NHANES) dataset (p < 0.005). Body mass index (BMI) accounted
      for only 6% of variance in non-HDL-C values (beta coefficient = 1.31, p < 0.05).
      CONCLUSIONS: Children and adolescents aged 8-17 years with TS appear to have a
      greater prevalence of adverse non-HDL-C levels compared to the general adolescent
      population. The prevalence of high non-HDL-C was not fully explained by BMI.

PMID- 28768283
TI  - Erratum.

PMID- 28768284
TI  - Prevalence of Traumatic Brain Injury in a Male Adult Prison Population and Its
      Association with the Offence Type.
AB  - BACKGROUND: The prevalence of traumatic brain injury (TBI) in prison populations
      has been found to vary considerably. This study aimed to determine the prevalence
      of TBI in a prison population in New Zealand and to identify whether age,
      ethnicity, offence type, security classification and sentence length were linked
      to TBI prevalence. METHODS: All offenders admitted to a new Corrections Facility
      over a 6-month period (May-November 2015) were screened to understand their
      history of TBI. Data was merged with demographic information, details of the
      offence type, sentence length and security classification from the prison
      database. Binary logistic regression was used to identify the contribution of
      predictors on TBI history. RESULTS: Of the 1,061 eligible male prisoners, 1,054
      (99.3%) completed a TBI history screen. Out of the 672 (63.7%) who had sustained
      at least one TBI in their lifetime, 343 (32.5%) had experienced multiple
      injuries. One in 5 participants experienced their first TBI injury before the age
      of 15 years. A regression model was able to correctly classify 66.9% of cases and
      revealed that belonging to Maori ethnicity or being imprisoned for violent,
      sexual or burglary offences were independently predictive of TBI (chi2 = 9.86, p
      = 0.28). CONCLUSIONS: The high prevalence of TBI within male prisoners and a high
      proportion of injuries sustained in childhood suggest the need for routine
      screening for TBI to identify prisoners at risk of persistent difficulties.
      Interventions to support those experiencing persistent difficulties post-TBI are
      needed to optimise functioning and prevent reoffending.

PMID- 28768285
TI  - Prevention of Diabetic Nephropathy by Modified Acidic Fibroblast Growth Factor.
AB  - BACKGROUND/AIMS: Oxidative stress (OS) contributes to all chronic diabetic
      complications, including diabetic nephropathy (DN). Acidic fibroblast growth
      factor (aFGF) has shown to confer protection from OS. However, it also has potent
      angiogenic activity. We hypothesized that a modified human aFGF (maFGF), with
      antioxidant properties but devoid of angiogenic activity, has preventative action
      in DN. METHODS: Streptozotocin-induced diabetic mice were treated with maFGF
      (intraperitoneally) daily for 1 or 6 months and were compared with untreated
      diabetic and non-diabetic controls. Microalbuminuria was assessed to determine
      functional damage. Renal cortical tissues were examined for multiple
      extracellular matrix proteins, vasoactive factors and OS markers. For mechanistic
      studies, immortalized mouse podocytes and human microvascular endothelial cells
      were exposed to high (25 mM) or low glucose (5 mM). OS, vasoactive factors,
      fibrosis and apoptosis-related gene expression were tested by real-time qPCR and
      Enzyme-Linked Immunosorbent Assay. Nitric oxide (NO) analyses were also
      performed. RESULTS: maFGF did not affect body weight and glycemia but prevented
      renal hypertrophy and functional changes in DN. It also prevented diabetes
      induced DNA damage, nitrosative stress, vasoactive factors, angiotensinogen and
      endothelial NO synthase alterations. Although it failed to prevent transforming
      growth factor (TGF)-beta1 mRNA upregulation, it prevented fibronectin production.
      Similar results were obtained in vitro. Decreased NO production in vivo and in
      vitro was also prevented by maFGF. CONCLUSIONS: maFGF treatment prevents DN. This
      prevention probably involves NO production.

PMID- 28768286
TI  - NICU Human Milk Dose and 20-Month Neurodevelopmental Outcome in Very Low Birth
      Weight Infants.
AB  - BACKGROUND: The association between human milk (HM) feeding in the NICU and
      neurodevelopmental (ND) outcome in very low birth weight (VLBW) infants is
      unclear. Limitations of previous studies include a lack of exact estimates of HM
      dose and of generalizability to minority populations. OBJECTIVE: To determine the
      impact on ND outcome of an exact dose of HM received in the NICU in a diverse,
      contemporary cohort of VLBW infants. METHODS: We included 430 VLBW infants born
      in the period 2008-2012 for whom the mean daily dose (DD) of HM received during
      the stay in the NICU (NICU HM-DD) was calculated prospectively from the daily
      nutritional intake from admission to discharge. Outcomes included Bayley-III
      index scores at 20 months' corrected age (CA) as assessed upon ND follow-up,
      which were collected retrospectively. Multivariable linear regression analyses
      controlled for neonatal and social risk factors. RESULTS: Each 10 mL/kg/day
      increase in NICU HM-DD was associated with a 0.35 increase in cognitive index
      score (95% CI [0.03-0.66], p = 0.03), but no significant associations were
      detected for the language or motor indices. CONCLUSIONS: There is a significant
      dose-dependent association between NICU HM intake and cognitive scores at 20
      months' CA. Further follow-up will determine whether these findings persist at
      school age, and could help alleviate the special-education and health-care burden
      in this population.

PMID- 28768287
TI  - The Association of Poor Academic Performance with Tic Disorders: A Longitudinal,
      Mainstream School-Based Population Study.
AB  - BACKGROUND: Little is known about the academic performance of students with tic
      disorders (TD). Our aim was to investigate the association of TD and poor
      academic performance over time. METHODS: Longitudinal, observational study of
      mainstream schoolchildren comparing grade retention (GR) and learning disorders
      (LD) in students with vs. without TD between 2010 and 2014. Students with vs.
      without TD based on DSM-IV-TR criteria, or with vs. without GR and LD were
      compared in terms of comorbidities, school, and environmental characteristics.
      The association of TD with GR was analyzed using hazard ratios (HRs) with 95%
      CIs, and with LD using logistic regression analysis [Odds ratio (OR)]. RESULTS:
      Two hundred fifty-eight students were included (mean age 14.0 +/- 1.71 years, 143
      [55.4%] males). The incident rate for TD and GR was 2.6 and 3.3 per 100 persons
      year, respectively. LD found in 21 (9.9%) students was associated with TD (OR
      11.62, 95% CI 2.21-60.90, p = 0.004), and attention deficit hyperactivity
      disorder (ADHD; OR 6.63, 95% CI 1.55-28.37, p = 0.01). Low psychological support
      (HRs 12.79, 95% CI 3.39-48.17) and low sport participation (HRs 6.41, 95% CI 1.54
      26.78) were risk factors for GR. CONCLUSIONS: TD was associated with academic
      difficulties, namely, LD in conjunction with ADHD but not GR. The diagnosis of TD
      and comorbidities, and the initiation of proper treatment could have a favorable
      impact on school performance, and consequently on social development.

PMID- 28768288
TI  - Reliability and Validity of a Smartphone-Paired Pulse Oximeter for Screening of
      Critical Congenital Heart Defects in Newborns.
AB  - BACKGROUND: Barriers to widespread implementation of pulse oximetry screening of
      critical congenital heart defects (CCHD) in newborns include increasing trends of
      out-of-hospital births and cost of equipment. In recent years, smartphone
      compatible pulse oximeters have appeared on the market, but the validity of such
      devices in the setting of CCHD screening has not been evaluated. OBJECTIVES: To
      compare the performance in CCHD screening of a smartphone-paired pulse oximeter
      (Masimo iSpO2-RxTM) and a hospital-grade pulse oximeter (Masimo Radical-7TM).
      METHODS: Preductal (right hand) and postductal (either foot) saturations were
      determined in a population of 201 term newborns by 2 independent teams, one using
      the Radical-7 and the other using the iSpO2-Rx. Bland-Altman analysis was applied
      to calculate mean bias and 95% limits of agreement between the 2 pulse oximeters.
      RESULTS: For the preductal oxygen saturation, the mean bias (Radical-7 minus
      iSpO2-Rx) was -0.08 (SD 1.76) and the lower and upper limits of agreement were 
      3.52 and 3.36, respectively. For the postductal oxygen saturation, the mean bias
      was -0.11 (SD 1.68) and the lower and upper limits of agreement were -3.49 and
      3.18, respectively. In addition, the iSpO2-Rx provided reliable measurements of
      saturations below 95% in a group of 12 infants admitted to the neonatal intensive
      care unit. CONCLUSIONS: Our data suggest that CCHD screening with the Masimo
      iSpO2-Rx is feasible and accurate. The use of reliable smartphone-paired pulse
      oximeters may contribute to the extension of CCHD screening to home births and
      low resource settings.

PMID- 28768289
TI  - beta-adrenergic Receptor-stimulated Cardiac Myocyte Apoptosis: Role of Cytochrome
      P450 omega-hydroxylase.
AB  - Prolonged or excessive beta-adrenergic activation leads to cardiac myocyte loss
      and heart dysfunction; however, the underlying cellular mechanisms are still
      unclear. Therefore, we first confirmed the effect of isoproterenol (ISO), a beta
      adrenergic receptor agonist, on cardiac toxicity using TUNEL and caspase activity
      assays in cultured rat cardiomyocytes. ISO treatment significantly increased
      cardiomyocyte apoptosis. Persistent ISO stimulation of cardiomyocytes also
      increased the expression of CYP4A3, a major CYP450 omega-hydroxylase that
      produces 20-hydroxyeicosatetraenoic acid (20-HETE) in a time-dependent manner.
      Next, we examined the effect of ISO and 20-HETE on cardiomyocyte apoptosis using
      annexin V and propidium iodide staining. Treatment with either 20-HETE or ISO
      significantly increased cardiomyocyte apoptosis, and inhibition of 20-HETE
      production using 17-ODYA, a CYP450 omega-hydroxylase inhibitor, dramatically
      attenuated ISO-induced cardiomyocyte apoptosis. To determine the apoptotic
      pathway involved, the mitochondrial membrane potential (DeltaPsim) was measured
      by detecting the ratio of JC-1 green/red emission intensity. The results
      demonstrated that 17-ODYA significantly abolished ISO-induced disruption of
      DeltaPsim and that 20-HETE alone induced a marked disruptive effect on DeltaPsim
      in cardiomyocytes. In addition, 20-HETE-induced disruption of DeltaPsim and
      apoptosis was significantly attenuated by KN93, a CaMKII inhibitor. Taken
      together, these results demonstrate that 20-HETE treatment induces significant
      apoptosis via mitochondrial-dependent pathways, and that inhibition of 20-HETE
      production using 17-ODYA attenuates ISO-induced cardiomyocyte apoptosis.

PMID- 28768290
TI  - Propofol Provides Cardiac Protection by Suppressing the Proteasome Degradation of
      Caveolin-3 in Ischemic/Reperfused Rat Hearts: Erratum.

PMID- 28768291
TI  - A requiem for BMI in the clinical setting.
AB  - PURPOSE OF REVIEW: Quetelet reported in the nineteenth century that body weight
      varies across adults with the square of height. Quetelet's index, now known as
      BMI, is accepted by most health organizations as a first-level measure of body
      fat and as a screening tool for diagnosing excess adiposity. Modern imaging
      methods now, however, indicate that BMI has limited predictive value for
      estimating body fat and lean mass at the individual level. The use of BMI as a
      measure of body composition in the clinical setting should therefore be
      challenged. RECENT FINDINGS: Recent studies enrolling cancer and surgical
      patients reported discrepant outcomes when BMI was used as a body composition
      surrogate. Sarcopenia, loss of muscle mass and function, which affects the
      elderly and those with chronic and acute diseases, is not accurately diagnosed
      with BMI. The distribution of adipose tissue is not characterized by BMI,
      specific measures of which have greater predictive value for metabolic
      impairments and clinical outcomes. SUMMARY: BMI, as the traditional tool for
      assessing malnutrition and obesity, is not appropriate to accurately
      differentiate between important body weight components and therefore should not
      be used for making clinically important decisions at the individual patient
      level.

PMID- 28768292
TI  - Assessing inflammageing.
AB  - PURPOSE OF REVIEW: Immunosenescence has been scrutinized in detail, and evidence
      that inflammation and ageing are interrelated is consistent. Still, a gold
      standard for assessing the biological age of the immune function in an individual
      patient is lacking, so that immunosenescence is still not a quantifiable
      criterion in clinical decision-making processes. RECENT FINDINGS: This review
      highlights recent (partly ongoing) studies into biomarkers of inflammation to
      assess immunosenescence, including large-scale studies, and quotes expert opinion
      statements. Markers of basal inflammation frequently used include interleukin-6,
      tumor necrosis factor-alpha and receptors p55 and p75, C-reactive protein and
      cytomegalovirus antibody levels. Some cellular markers are particularly advocated
      to reflect age-related decay of specific immunity, namely the decrease of naive T
      cells, especially CD8cells, and accumulations of memory T cells, especially late
      stage differentiated CD8 cells; the loss of CD28 on lymphocytes is also taken as
      a biomarker of immunosenescence. SUMMARY: Substantial progress has been made in
      both understanding and phenotyping immunosenescence and inflammageing. The
      diagnosis of the degree of immunosenescence in the individual patient, however,
      has not yet been standardized.

PMID- 28768293
TI  - Omega-3 index as a prognosis tool in cardiovascular disease.
AB  - PURPOSE OF REVIEW: In 2004, the 'Omega-3 index' was described as the sum of
      eicosapentaenoic acid (EPA, 20 : 5 n-3) and docosahexaenoic acid (DHA, 22 : 6 n
      3) in red blood cells (RBCs) as an index of coronary heart disease mortality.
      This review outlines new evidence to support the Omega-3 index as a tool to
      inform disease prognosis. RECENT FINDINGS: Recent studies have reported
      differential metabolism of EPA and DHA. High-dose supplementation with EPA and
      DHA led to increased levels of RBC DHA that were associated with decreased liver
      fat. EPA and DHA in RBCs were associated with reduced mortality in a prospective
      study of patients with cardiac disease; the strongest association was with EPA. A
      diet containing 9.5-g alpha-linolenic acid lead to an increase in EPA but not DHA
      status in middle-aged women. SUMMARY: Dietary intake or supplementation studies
      with n-3 fatty acids should include measurement of n-3 status in a standardized
      way. The Omega-3 index, reflecting EPA and DHA status throughout the body, is
      convenient and may be appropriate in some cases, but as EPA and DHA assimilate
      differently in membranes, and have different potency, measurement of individual
      fatty acid composition in RBCs may be more informative.

PMID- 28768294
TI  - Measurement of metabolic fluxes using stable isotope tracers in whole animals and
      human patients.
AB  - PURPOSE OF REVIEW: Metabolic flux analysis using stable isotope labeled
      substrates allows for the tracing of carbon, nitrogen, and hydrogen atoms through
      metabolic pathways and is an invaluable tool for investigating dynamic metabolic
      changes occurring in health and disease. Studies of flux analysis in vivo are
      more technically challenging than in vitro or ex vivo but provide a highly
      detailed view of organ and/or systemic metabolism. We review here recent efforts
      in studies of diet and nutrition, non-small cell lung cancer,
      ischemia/reperfusion injury, and hemorrhagic shock where in vivo flux analysis
      was utilized to analyze metabolic modulation. RECENT FINDINGS: Recent technical
      strides in the field of metabolomics afford sensitive and quantitative in vivo
      measurements of metabolic fluxes. Stable isotope tracing with C-glucose, C, N
      glutamine, C-propionate, and other substrates are used in combination or in
      parallel to investigate the interplays among central carbon metabolic pathways
      and many other areas of the metabolome. SUMMARY: Stable isotope tracing in vivo
      provides opportunities to investigate physiological processes in the context of
      the whole animal. These approaches, often NMR spectroscopy or mass spectrometry
      (MS)-based, are growing in use and will likely find key applications in studying
      systemic disease, sports physiology, cancer metabolism, and personalized
      medicine.

PMID- 28768295
TI  - Exclusive enteral nutrition for inducing remission in inflammatory bowel disease
      in paediatric patients.
AB  - PURPOSE OF REVIEW: Enteral nutrition as a treatment for inflammatory bowel
      diseases is an ongoing area of interest. Even in the era of biologic agents,
      exclusive enteral nutrition (EEN) offers a unique, drug-free measure for
      induction of remission in luminal Crohn's disease. The purpose of this review is
      to discuss the role of EEN in the evolving therapeutic scheme for Crohn's
      disease, to report on new evidence for short and long-term efficacy and highlight
      findings on the mechanisms of the anti-inflammatory effects of EEN in light of
      current understanding of disease pathogenesis. RECENT FINDINGS: Recent clinical
      studies have suggested that EEN has an established advantage over corticosteroids
      for inducing remission in children with luminal Crohn's disease with comparable
      clinical efficacy but superior mucosal healing effect as well as better safety
      profile. Preoperative EEN therapy can also improve postoperative outcome of
      intestinal resection. Basic research has demonstrated that EEN has direct anti
      inflammatory properties, can correct localization of tight junction proteins,
      alter micro RNAs expression, and profoundly affect the intestinal microbiota.
      SUMMARY: EEN is an effective treatment for induction of remission in pediatric
      luminal Crohn's disease and should be offered as a first-line treatment.
      Accumulating evidence suggest that EEN has direct anti-inflammatory properties
      with an effect on the intestinal microbiota. However, the relationships between
      these effects and the specific triggers for these changes have yet to be
      elucidated.

PMID- 28768296
TI  - Dietary pattern and colonic diverticulosis.
AB  - PURPOSE OF REVIEW: To assess the role of dietary pattern on the occurrence of
      colonic diverticulosis, diverticular disease and acute diverticulitis. RECENT
      FINDINGS: High-fiber diet does not prevent diverticulosis occurrence, and results
      about prevention/treatment of diverticular disease and acute diverticulitis are
      still conflicting.No association was seen between nut, corn or popcorn
      consumption and occurrence of diverticulosis, diverticular disease and acute
      diverticulitis.It seems to be a mild association between high alcohol intake and
      diverticulosis occurrence, whereas alcohol dependence seems to show lower risk of
      in-hospital mortality due to acute diverticulitis.Higher red-meat consumption
      shows mild increased risk of acute diverticulitis, especially when consumed as
      unprocessed red meat (defined as consumption of 'beef or lamb as main dish',
      'pork as main dish', 'hamburger' and 'beef, pork or lamb as a sandwich or mixed
      dish'); higher consumption of poultry (viz. white meat) was not associated with
      risk of acute diverticulitis.Finally, higher fish intake was associated with
      reduced risk of diverticulitis in age-adjusted model, but not after further
      adjustment for other potential confounders. SUMMARY: Current literature data
      about the role of dietary pattern on the occurrence of colonic diverticulosis,
      diverticular disease and acute diverticulitis are still too conflicting.

PMID- 28768297
TI  - Whats 'App-ening': the help of new technologies in nutrition in digestive
      diseases.
AB  - PURPOSE OF REVIEW: The aim of this study is to review the basic concepts of
      electronic health (eHealth), with a focus on its nutritional applications and its
      usefulness for digestive diseases. RECENT FINDINGS: eHealth applications for the
      treatment and monitoring of digestive disease are growing in number. ehealth
      helps patients in coping with their disease by promoting self-management, which
      increases adherence to medical treatment and diets, and leads to an improved
      quality of life. For irritable bowel syndrome (IBS), there are multiple
      applications that provide dietary advice, for example, a low FODMAP (Fermentable
      Oligo, Mono, Disaccharides And Polyols) diet. However, many applications lack a
      symptom scoring function and do not include a module for assisting the essential
      reintroduction of high FODMAP foods. In general, there are very few applications
      that enable direct patient communication with healthcare professionals. A more
      holistic approach that educates patients and enables them to communicate directly
      with eCare provider through a web application is one of the functions most
      requested by patients. SUMMARY: eHealth solutions for digestive diseases have a
      supportive function and a positive impact on patients. However, there is a need
      to increase patient education and further develop the possibility for care team
      patient communication within eHealth solutions.

PMID- 28768298
TI  - Estimating the Causal Effect of Low Levels of Fine Particulate Matter on
      Hospitalization.
AB  - BACKGROUND: In 2012, the EPA enacted more stringent National Ambient Air Quality
      Standards (NAAQS) for fine particulate matter (PM2.5). Few studies have
      characterized the health effects of air pollution levels lower than the most
      recent NAAQS for long-term exposure to PM2.5 (now 12 MUg/m). METHODS: We
      constructed a cohort of 32,119 Medicare beneficiaries residing in 5138 US ZIP
      codes who were interviewed as part of the Medicare Current Beneficiary Survey
      (MCBS) between 2002 and 2010 and had 1 year of follow-up. We considered four
      outcomes: all-cause hospitalizations, hospitalizations for circulatory diseases
      and respiratory diseases, and death. RESULTS: We found that increasing exposure
      to PM2.5 from levels lower than 12 MUg/m to levels higher than 12 MUg/m is
      associated with increases in all-cause admission rates of 7% (95% CI = 3%, 10%)
      and in circulatory admission hazard rates of 6% (95% CI = 2%, 9%). When we
      restricted analysis to enrollees with exposure always lower than 12 MUg/m, we
      found that increasing exposure from levels lower than 8 MUg/m to levels higher
      than 8 MUg/m increased all-cause admission hazard rates by 15% (95% CI = 8%,
      23%), circulatory by 18% (95% CI = 10%, 27%), and respiratory by 21% (95% CI =
      9%, 34%). CONCLUSIONS: In a nationally representative sample of Medicare
      enrollees, changes in exposure to PM2.5, even at levels consistently below
      standards, are associated with increases in hospital admissions for all causes
      and cardiovascular and respiratory diseases. The robustness of our results to
      inclusion of many additional individual level potential confounders adds validity
      to studies of air pollution that rely entirely on administrative data.

PMID- 28768299
TI  - A Prospective Investigation of Coffee Drinking and Bladder Cancer Incidence in
      the United States.
AB  - BACKGROUND: In 1991, coffee was classified as a group 2B carcinogen, possibly
      carcinogenic to humans, based on limited epidemiologic evidence of a positive
      association with bladder cancer. In 2016, the International Agency for Research
      on Cancer downgraded this classification due to lack of evidence from prospective
      studies particularly for never smokers. METHODS: Baseline coffee drinking was
      assessed with a food frequency questionnaire in the NIH-AARP prospective cohort
      study. Among 469,047 US adults, who were cancer free at baseline, 6,012 bladder
      cancer cases (5,088 men and 924 women) were identified during >6.3 million person
      years of follow-up. Multivariable-adjusted Cox proportional hazards models were
      used to estimate hazard ratios (HR) and 95% confidence intervals (CI), with non
      coffee drinkers as the reference group. RESULTS: Coffee drinking was positively
      associated with bladder cancer in models adjusted for age and sex (HR for >=4
      cups/d relative to coffee nondrinkers = 1.91, 95% CI = 1.70, 2.14; P trend <
      0.0001). However, the association was substantially attenuated after adjustment
      for cigarette smoking and other potential confounders (HR for >=4 cups/d relative
      to coffee nondrinkers = 1.18, 95% CI = 1.05, 1.33; P trend = 0.0007).
      Associations were further attenuated after additional adjustment for lifetime
      smoking patterns among the majority of the cohort with this available data (P
      trend = 0.16). There was no evidence of an association among never smokers (P
      trend = 0.84). CONCLUSIONS: Positive associations between coffee drinking and
      bladder cancer among ever smokers but not never smokers suggest that residual
      confounding from imperfect measurement of smoking or unmeasured risk factors may
      be an explanation for our positive findings.

PMID- 28768300
TI  - Androgen Deprivation Therapy and the Risk of Anemia in Men with Prostate Cancer.
AB  - BACKGROUND: The use of androgen deprivation therapy in prostate cancer may be
      associated with an increased risk of anemia, but the evidence remains limited.
      This study aimed to determine if androgen deprivation is associated with
      increased risk of anemia in patients newly diagnosed with prostate cancer.
      METHODS: This was a population-based cohort study using the United Kingdom
      Clinical Practice Research Datalink linked to the Hospital Episode Statistics
      repository. The cohort consisted of 10,364 men newly diagnosed with nonmetastatic
      prostate cancer between 1 April 1998 and 30 September 2015. We used time
      dependent Cox proportional hazards models to estimate adjusted hazard ratios
      (HRs) and 95% confidence intervals (CIs) for anemia (hemoglobin <130 g/L)
      associated with current and past use of androgen deprivation therapy, compared
      with nonuse. RESULTS: There were 3,651 incident anemia events during 31,574
      person-years of follow-up (rate: 11.6/100 person-years). Current androgen
      deprivation therapy use was associated with a nearly three-fold increased hazard
      of anemia, compared with nonuse (23.5 vs. 5.9 per 100 person-years, respectively;
      HR: 2.90, 95% CI: 2.67, 3.16). The HR was elevated in the first 6 months of use
      (HR: 2.20, 95% CI: 1.95, 2.48) and continued to be elevated with longer durations
      of use. Past androgen deprivation therapy use was associated with a lower
      estimate (HR: 1.27, 95% CI: 1.12, 1.43), which returned closer to the null >=25
      months after treatment discontinuation (HR: 0.95, 95% CI: 0.79, 1.15).
      CONCLUSIONS: The use of androgen deprivation therapy is associated with increased
      risk of anemia, which reverses upon treatment discontinuation.

PMID- 28768302
TI  - Treatment Prediction, Balance, and Propensity Score Adjustment.

PMID- 28768301
TI  - Representativeness of Medicare Participants in the Jackson Heart Study for
      African American Medicare Beneficiaries.
AB  - BACKGROUND: The Jackson Heart Study (JHS) assesses cardiovascular disease risk
      factors among African Americans in Jackson, Mississippi. Whether characteristics
      of JHS participants differ from those of a broader African American population
      are unknown. METHODS: In a retrospective observational analysis, we compared
      characteristics and outcomes of JHS participants 65 years old and older and
      enrolled in Medicare (n = 1,105) to regional (n = 57,489) and national (n =
      95,494) cohorts of African American Medicare beneficiaries. We weighted the
      regional and national cohorts to match the age and sex distributions of the JHS
      Medicare cohort for pairwise baseline comparisons. Outcomes of interest included
      mortality and Medicare costs. We used Cox proportional hazards models to test
      associations between cohorts and outcomes. RESULTS: The JHS-Medicare cohort was
      younger, included more women, and had fewer beneficiaries with dual Medicare
      Medicaid eligibility, compared with regional and national Medicare cohorts. The
      cohort also had lower risks of stroke, lung disease, heart failure, diabetes, and
      renal disease. Mean Medicare costs were lower ($5,066 [SD = $11,932]) than in the
      regional ($7,419 [SD = $17,574]) and national ($8,013 [SD = $19,378]) cohorts.
      The regional and national cohorts had higher mortality (adjusted hazard ratios =
      1.52; 95% confidence interval [CI] = 1.31, 1.76; and 1.49; 95% CI = 1.29, 1.73,
      respectively). Subgroup analysis for dual Medicare-Medicaid eligibility
      attenuated mortality differences. CONCLUSION: JHS-Medicare participants had fewer
      comorbid conditions, better survival, and lower Medicare costs compared with
      regional and national cohorts. Observed differences may reflect healthy volunteer
      bias and higher socioeconomic status.See video abstract at,
      http://links.lww.com/EDE/B235.

PMID- 28768304
TI  - The Importance of Breast Conservation Therapy in Young Women: Breast Conservation
      in the Young.

PMID- 28768303
TI  - Beyond the Margins-Economic Costs and Complications Associated With Repeated
      Breast-Conserving Surgeries.

PMID- 28768306
TI  - Low-Density Lipoprotein Cholesterol and Drug Treatment to Lower Atherosclerotic
      Cardiovascular Disease Risk: Where Do We Stand?

PMID- 28768305
TI  - Patient Perceptions of Primary Care-Based Skin Cancer Screening.

PMID- 28768307
TI  - Repurposing Medications-Chicken Manure, Erectile Dysfunction, and Finding the
      Golden Needle in the Haystack of Absurdity.

PMID- 28768309
TI  - Age Range Error in Key Points, Abstract, Introduction, and Figure Caption.

PMID- 28768308
TI  - Secukinumab-Induced Psoriasiform Eruption.

PMID- 28768310
TI  - Low-Density Lipoprotein Cholesterol Treatment in the Proprotein Convertase
      Subtilisin/Kexin Type 9 Inhibitor Era: Getting Back on Target.

PMID- 28768311
TI  - Temporal Relation Between Myocardial Fibrosis and Heart Failure With Preserved
      Ejection Fraction: Association With Baseline Disease Severity and Subsequent
      Outcome.
AB  - Importance: Among myriad changes occurring during the evolution of heart failure
      with preserved ejection fraction (HFpEF), cardiomyocyte-extracellular matrix
      interactions from excess collagen may affect microvascular, mechanical, and
      electrical function. Objective: To investigate whether myocardial fibrosis (MF)
      is similarly prevalent both in those with HFpEF and those at risk for HFpEF,
      similarly associating with disease severity and outcomes. Design, Setting, and
      Participants: Observational cohort study from June 1, 2010, to September 17,
      2015, with follow-up until December 14, 2015, at a cardiovascular magnetic
      resonance (CMR) center serving an integrated health system. Consecutive patients
      with preserved systolic function referred for CMR were eligible. Cardiovascular
      magnetic resonance was used to exclude patients with cardiac amyloidosis (n =
      19). Exposures: Myocardial fibrosis quantified by extracellular volume (ECV) CMR
      measures. Main Outcome and Measures: Baseline BNP; subsequent hospitalization for
      heart failure or death. Results: Of 1174 patients identified (537 [46%] female;
      median [interquartile range {IQR}] age, 56 [44-66] years), 250 were "at risk" for
      HFpEF given elevated brain-type natriuretic peptide (BNP) level; 160 had HFpEF by
      documented clinical diagnosis, and 745 did not have HFpEF. Patients either at
      risk for HFpEF or with HFpEF demonstrated similarly higher prevalence/extent of
      MF and worse prognosis compared with patients with no HFpEF. Among those at risk
      for HFpEF or with HFpEF, the actual diagnosis of HFpEF was not associated with
      significant differences in MF (median ECV, 28.2%; IQR, 26.2%-30.7% vs 28.3%; IQR,
      25.5%-31.4%; P = .60) or prognosis (log-rank 0.8; P = .38). Over a median of 1.9
      years, 61 patients at risk for HFpEF or with HFpEF experienced adverse events (19
      hospitalization for heart failure, 48 deaths, 6 with both). In those with HFpEF,
      ECV was associated with baseline log BNP (disease severity surrogate) in
      multivariable linear regression models, and was associated with outcomes in
      multivariable Cox regression models (eg, hazard ratio 1.75 per 5% increase in
      ECV, 95% CI, 1.25-2.45; P = .001 in stepwise model) whether grouped with patients
      at risk for HFpEF or not. Conclusions and Relevance: Among myriad changes
      occurring during the apparent evolution of HFpEF where elevated BNP is prevalent,
      MF was similarly prevalent in those with or at risk for HFpEF. Conceivably, MF
      might precede clinical HFpEF diagnosis. Regardless, MF was associated with
      disease severity (ie, BNP) and outcomes. Whether cells and secretomes mediating
      MF represent therapeutic targets in HFpEF warrants further evaluation.

PMID- 28768313
TI  - Treatment of Hailey-Hailey Disease With Low-Dose Naltrexone.
AB  - Importance: Hailey-Hailey disease is a severe genetic blistering disease of
      intertriginous skin locations that can lead to poor quality of life and increased
      morbidities. Multiple therapies are available with inconsistent outcomes and
      potentially severe adverse effects. Objective: To determine whether low-dose
      naltrexone is an effective treatment for Hailey-Hailey disease. Design, Setting,
      and Participants: This study was a case series performed at a dermatology
      outpatient clinic of 3 patients with severe Hailey-Hailey disease recalcitrant to
      at least 4 therapies. Interventions: Low-dose naltrexone, 3 mg nightly, titrated
      to 4.5 mg nightly in 2 patients. Main Outcomes and Measures: Reduction in size of
      lesions as well as subjective improvement of symptoms. Results: All 3 patients
      noted significant healing of erosions and plaques starting from the peripheral
      aspect within 1 to 2 weeks of treatment, and clinical resolution of lesions
      within 2 months. Discontinuation of low-dose naltrexone resulted in flaring of
      symptoms, which cleared within 2 to 3 days on rechallenge with low-dose
      naltrexone. Conclusions and Relevance: We present herein 3 cases of patients with
      severe Hailey-Hailey disease treated with low-dose naltrexone who achieved
      clinical resolution of symptoms. The success of these cases suggests low-dose
      naltrexone as a novel therapy for Hailey-Hailey disease. The possible mechanism
      may involve low-dose naltrexone influencing opioid or toll-like receptor
      signaling to improve calcium mobilization and improve keratinocyte
      differentiation and wound healing. Future studies are needed to clarify the
      mechanism and to define the role of low-dose naltrexone for treatment of Hailey
      Hailey disease.

PMID- 28768312
TI  - Association of White Matter With Core Cognitive Deficits in Patients With
      Schizophrenia.
AB  - Importance: Efforts to remediate the multiple cognitive function impairments in
      schizophrenia should consider white matter as one of the underlying neural
      mechanisms. Objective: To determine whether altered structural brain connectivity
      is responsible for 2 of the core cognitive deficits in schizophrenia- reduced
      information processing speed and impaired working memory. Design, Setting, and
      Participants: This cross-sectional study design took place in outpatient clinics
      from August 1, 2004, to August 31, 2015. Participants included 166 patients with
      schizophrenia and 213 healthy control individuals. These participants were from 3
      independent cohorts, each of which had its own healthy control group. No
      participant had current or past neurological conditions or major medical
      conditions. Patients were diagnosed with either schizophrenia or schizoaffective
      disorder as defined by the DSM-IV. Controls had no Axis I psychiatric disorder.
      Main Outcomes and Measures: Mediation analyses and structural equation modeling
      were used to analyze the associations among processing speed, working memory, and
      white matter microstructures. Whole-brain and regional diffusion tensor imaging
      fractional anisotropy were used to measure white matter microstructures. Results:
      Of the study participants, the 166 patients with schizophrenia had a mean (SD)
      age of 38.2 (13.3) years and the 213 healthy controls had a mean (SD) age of 39.2
      (14.0) years. There were significantly more male patients than controls in each
      of the 3 cohorts (117 [70%] vs 91 [43%]), but there were no significant
      differences in sex composition among the 3 cohorts. Patients had significantly
      reduced processing speed (Cohen d = 1.24; P = 6.91 * 10-30) and working memory
      deficits (Cohen d = 0.83; P = 1.10 * 10-14) as well as a significant whole-brain
      fractional anisotropy deficit (Cohen d = 0.63; P = 2.20 * 10-9). In
      schizophrenia, working memory deficit was mostly accounted for by processing
      speed deficit, but this deficit remained when accounting for working memory
      (Cohen d = 0.89; P = 2.21 * 10-17). Mediation analyses showed a significant
      association pathway from fractional anisotropy to processing speed to working
      memory (P = 5.01 * 10-7). The strength of this brain-to-cognition pathway in
      different white matter tracts was strongly associated with the severity of
      schizophrenia-associated fractional anisotropy deficits in the corresponding
      white matter tracts as determined by a meta-analysis (r = 0.85-0.94; all P <
      .001). The same pattern was observed in patients and controls either jointly or
      independently. Conclusions and Relevance: Study findings suggest that (1)
      processing speed contributes to the association between white matter
      microstructure and working memory in schizophrenia and (2) white matter
      impairment in schizophrenia is regional tract-specific, particularly in tracts
      normally supporting processing speed performance.

PMID- 28768314
TI  - Low-Dose Naltrexone Treatment of Familial Benign Pemphigus (Hailey-Hailey
      Disease).
AB  - Importance: Familial benign pemphigus, or Hailey-Hailey disease (HHD), is a rare
      and debilitating genetic dermatosis characterized by chronic, recurrent vesicles,
      erosions, and maceration in flexural areas. Despite the reported therapeutic
      modalities, such as topical and systemic corticosteroids, systemic
      immunomodulators, topical and systemic retinoids, and laser, HHD can still be
      markedly difficult to control. Objective: To assess low-dose naltrexone
      hydrochloride in the treatment of recalcitrant HHD. Design, Setting, and
      Participants: In this case series, 3 patients with biopsy-proven recalcitrant HHD
      were evaluated in the outpatient dermatology clinic at the Cleveland Clinic. Each
      patient was treated with low-dose naltrexone hydrochloride at a dosage of 1.5 to
      3.0 mg per day. No laboratory monitoring was necessary. Clinical response
      (healing of erosions, improvement in erythema, and alleviation of pain), adverse
      effects, and subjective quality of life were monitored throughout the treatment.
      The study dates were January 2016 to January 2017. Main Outcomes and Measures:
      Objective clinical response as assessed by the treating dermatologist, subjective
      quality of life as reported by the patient, and recorded adverse effects were
      monitored throughout the treatment at intervals of 2 to 3 months. Results: The 3
      patients included a woman in her 40s and 2 men in their 60s. Each patient
      exhibited at least an 80% improvement in extent of disease, with one patient
      demonstrating 90% clearance. All 3 patients had substantial improvement in
      quality of life, with one patient reporting improvement in his depression. No
      adverse effects were recorded. Conclusions and Relevance: Low-dose naltrexone may
      represent a low-cost and low-risk alternative or adjunct in the treatment of HHD.

PMID- 28768315
TI  - An International Human Cell Atlas Consortium Takes Shape.

PMID- 28768316
TI  - Interactional Dysfunction of the Social Brain in a Paradigmatic Relational
      Disorder: From One Island to Another.

PMID- 28768317
TI  - Hue shifts produced by temporal asymmetries in chromatic signals.
AB  - Observers viewed M- or L-cone-isolating stimuli and compared slowly-on and slowly
      off sawtooth waveforms of the same mean chromaticity and luminance. Between 6 and
      13 Hz, the mean hue of slowly-on L-cone and slowly-off M-cone sawtooth flicker
      appeared redder, and the mean hue of slowly-off L-cone and slowly-on M-cone
      sawtooth stimuli appeared greener-despite all the waveforms' having the same
      mean, near-yellow-appearing chromaticity. We measured the effect of the
      modulation depth and the slope of the sawtooth on the mean hue shifts as a
      function of temporal frequency. The results are complex but show that
      discriminability depended mainly on the second harmonic of the waveforms. We
      considered several models with combinations of linear and nonlinear stages.
      First, we considered models in which a nonlinear stage limits the rate of change
      of hue and restricts the steep slope of the sawtooth waveform more than its
      shallow slope, thus shifting the mean hue in the direction of the shallower slope
      (such a nonlinearity is also known as a slew-rate limit). Second, we considered
      saturation models in which the nonlinear stage compresses hue signals and thus
      shifts the mean of asymmetrical waveforms with or without differentiation before
      the nonlinearity. Overall, our modeling and results suggest that the hue shift
      occurs at some nonlinear mechanism in the chromatic pathway; and that, in terms
      of the Fourier components of the various waveforms, the effect of the
      nonlinearity depends crucially on the timing of the second harmonic relative to
      the first.

PMID- 28768318
TI  - Hue shifts produced by temporal asymmetries in chromatic signals depend on the
      alignment of the first and second harmonics.
AB  - When M- or L-cone-isolating sawtooth waveforms flicker at frequencies between 4
      and 13.3 Hz, there is a mean hue shift in the direction of the shallower sawtooth
      slope. Here, we investigate how this shift depends on the alignment of the first
      and second harmonics of sawtooth-like waveforms. Below 4 Hz, observers can follow
      hue variations caused by both harmonics, and reliably match reddish and greenish
      excursions. At higher frequencies, however, the hue variations appear as
      chromatic flicker superimposed on a steady light, the mean hue of which varies
      with second-harmonic alignment. Observers can match this mean hue against a
      variable-duty-cycle rectangular waveform and, separately, set the alignment at
      which the mean hue flips between reddish and greenish. The maximum hue shifts
      were approximately frequency independent and occurred when the peaks or troughs
      of the first and second harmonics roughly aligned at the visual input-consistent
      with the hue shift's being caused by an early instantaneous nonlinearity that
      saturates larger hue excursions. These predictions, however, ignore phase delays
      introduced within the chromatic pathway between its input and the nonlinearity
      that produces the hue shifts. If the nonlinearity follows the substantial
      filtering implied by the chromatic temporal contrast-sensitivity function, phase
      delays will alter the alignment of the first and second harmonics such that at
      the nonlinearity, the waveforms that produce the maximum hue shifts might well be
      those with the largest differences in rising and falling slopes-consistent with
      the hue shift's being caused by a central nonlinearity that limits the rate of
      hue change.

PMID- 28768319
TI  - Evaluating Random Error in Clinician-Administered Surveys: Theoretical
      Considerations and Clinical Applications of Interobserver Reliability and
      Agreement.
AB  - Purpose: The purpose of this study is to raise awareness of interobserver
      concordance and the differences between interobserver reliability and agreement
      when evaluating the responsiveness of a clinician-administered survey and,
      specifically, to demonstrate the clinical implications of data types
      (nominal/categorical, ordinal, interval, or ratio) and statistical index
      selection (for example, Cohen's kappa, Krippendorff's alpha, or interclass
      correlation). Methods: In this prospective cohort study, 3 clinical audiologists,
      who were masked to each other's scores, administered the Practical Hearing Aid
      Skills Test-Revised to 18 adult owners of hearing aids. Interobserver concordance
      was examined using a range of reliability and agreement statistical indices.
      Results: The importance of selecting statistical measures of concordance was
      demonstrated with a worked example, wherein the level of interobserver
      concordance achieved varied from "no agreement" to "almost perfect agreement"
      depending on data types and statistical index selected. Conclusions: This study
      demonstrates that the methodology used to evaluate survey score concordance can
      influence the statistical results obtained and thus affect clinical
      interpretations.

PMID- 28768320
TI  - Effects of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of
      Patients With Heart Failure: Proposal of a Novel Mechanism of Action.
AB  - Importance: Only 1 class of glucose-lowering agents-sodium-glucose cotransporter
      2 (SGLT2) inhibitors-has been reported to decrease the risk of cardiovascular
      events primarily by reducing the risk of the development or progression of heart
      failure. In a landmark trial called Empagliflozin, Cardiovascular Outcomes, and
      Mortality in Type 2 Diabetes [EMPA-REG Outcomes], long-term treatment with
      empagliflozin prevented fatal and nonfatal heart failure events but did not
      reduce the risk of myocardial infarction or stroke in diabetic patients.
      Observations: The beneficial effect of SGLT2 inhibitors on heart failure cannot
      be explained by their actions on glycemic control or as osmotic diuretics.
      Instead, in the kidneys, SGLT2 functionally interacts with the sodium-hydrogen
      exchanger, which is responsible for the majority of sodium tubular reuptake
      following filtration. The activity of sodium-hydrogen exchanger is markedly
      increased in patients with heart failure and may be responsible for both
      resistance to diuretics and to endogenous natriuretic peptides. In addition, in
      the heart, empagliflozin appears to inhibit sodium-hydrogen exchange, which may
      in turn lead to a reduction in cardiac injury, hypertrophy, fibrosis, remodeling,
      and systolic dysfunction. Furthermore, the major pathophysiological derangements
      of heart failure and a preserved ejection fraction may be mitigated by the
      actions of SGLT2 inhibitors to reduce blood pressure, body weight, and fluid
      retention as well as to improve renal function. The benefits of spironolactone in
      patients with heart failure with either a reduced or a preserved ejection
      fraction may also be attributable to the actions of the drug to inhibit the
      sodium-hydrogen exchange mechanism. Conclusions and Relevance: The benefits of
      SGLT2 inhibitors in heart failure may be mediated by the inhibition of sodium
      hydrogen exchange rather than the effect on glucose reabsorption. This hypothesis
      has important implications for the design and analysis of large-scale outcomes
      trials involving diabetic or nondiabetic patients with chronic heart failure.

PMID- 28768321
TI  - Leber's Hereditary Optic Neuropathy-Specific Mutation m.11778G>A Exists on
      Diverse Mitochondrial Haplogroups in India.
AB  - Purpose: Leber's hereditary optic neuropathy (LHON; OMIM 535000) is one of the
      most common maternally inherited mitochondrial disorders. Three mitochondrial DNA
      point mutations-m.3460G>A (MT-ND1), m.11778G>A (MT-ND4), and m.14484T>C (MT-ND6)
      account for the majority of reported LHON cases. Only approximately 50% of males
      and approximately 10% of females carrying these mutations develop optic
      neuropathy and blindness. Additional factors, such as mtDNA/nuclear genetic
      background and environmental modifiers, are likely to contribute toward the
      observed incomplete penetrance and gender bias. We aimed to investigate whether
      mtDNA haplogroup influences LHON clinical expression in Indian patients harboring
      the m.11778G>A mutation. Methods: Detailed clinical assessment and complete
      mitochondrial genome sequencing was undertaken in 64 LHON families harboring the
      m.11778G>A mutation. Mitochondrial haplogroup was assigned based on
      evolutionarily conserved mtDNA variations. Results: A total of 543 individuals
      (295 male, 248 female) from 64 unrelated families harboring the m.11778G>A
      mutation were recruited to the study. The overall disease penetrance was 27.07%
      (146 of 543) and higher in males (37.9%; 112 of 295) than females (13.7%; 34 of
      248). The mtDNA haplogroup analysis revealed that all affected probands belonged
      to different mtDNA haplogroups. No association between the m.11778G>A mutation
      and the background mtDNA haplogroup was detected. Conclusions: The first detailed
      study of Indian LHON patients confirm that the m.11778G>A-related LHON in India
      coexists with multiple different mtDNA haplogroups, unlike the preferential
      association of west Eurasian haplogroup J and the reported increased clinical
      penetrance with the J2 subhaplogroup. However, we observed variable penetrance of
      LHON in different Indian mtDNA haplogroup backgrounds, indicating their possible
      influence on clinical expression. These data suggest that a similar
      heterogeneity, resulting from the mtDNA haplogroup, might also exist in other
      mitochondrial diseases among Indian populations.

PMID- 28768323
TI  - The Importance of a Valid Comparison Group-Reply.

PMID- 28768322
TI  - State-Dependent Cross-Brain Information Flow in Borderline Personality Disorder.
AB  - Importance: Although borderline personality disorder (BPD)-one of the most
      common, burdensome, and costly psychiatric conditions-is characterized by
      repeated interpersonal conflict and instable relationships, the neurobiological
      mechanism of social interactive deficits remains poorly understood. Objective: To
      apply recent advancements in the investigation of 2-person human social
      interaction to investigate interaction difficulties among people with BPD.
      Design, Setting, and Participants: Cross-brain information flow in BPD was
      examined from May 25, 2012, to December 4, 2015, in pairs of participants studied
      in 2 linked functional magnetic resonance imaging scanners in a university
      setting. Participants performed a joint attention task. Each pair included a
      healthy control individual (HC) and either a patient currently fulfilling DSM-IV
      criteria for BPD (cBPD) (n = 23), a patient in remission for 2 years or more
      (rBPD) (n = 17), or a second HC (n = 20). Groups were matched for age and
      educational level. Main Outcomes and Measures: A measure of cross-brain neural
      coupling was computed following previously published work to indicate
      synchronized flow between right temporoparietal junction networks (previously
      shown to host neural coupling abilities in health). This measure is derived from
      an independent component analysis contrasting the time courses of components
      between pairs of truly interacting participants compared with bootstrapped
      control pairs. Results: In the sample including 23 women with cBPD (mean [SD]
      age, 26.8 [5.7] years), 17 women with rBPD (mean [SD] age, 28.5 [4.3] years), and
      80 HCs (mean [SD] age, 24.0 [3.4] years]) investigated as dyads, neural coupling
      was found to be associated with disorder state (eta2 = 0.17; P = .007): while HC
      HC pairs showed synchronized neural responses, cBPD-HC pairs exhibited
      significantly lower neural coupling just above permutation-based data levels
      (eta2 = 0.16; P = .009). No difference was found between neural coupling in rBPD
      HC and HC-HC pairs. The neural coupling in patients was significantly associated
      with childhood adversity (T = 2.3; P = .03). Conclusions and Relevance: This
      study provides a neural correlate for a core diagnostic and clinical feature of
      BPD. Results indicate that hyperscanning may deliver state-associated biomarkers
      for clinical social neuroscience. In addition, at least some neural deficits of
      BPD may be more reversible than is currently assumed for personality disorders.

PMID- 28768324
TI  - Speech Understanding in Noise by Patients With Cochlear Implants Using a Monaural
      Adaptive Beamformer.
AB  - Purpose: The aim of this experiment was to compare, for patients with cochlear
      implants (CIs), the improvement for speech understanding in noise provided by a
      monaural adaptive beamformer and for two interventions that produced bilateral
      input (i.e., bilateral CIs and hearing preservation [HP] surgery). Method: Speech
      understanding scores for sentences were obtained for 10 listeners fit with a
      single CI. The listeners were tested with and without beamformer activated in a
      "cocktail party" environment with spatially separated target and maskers. Data
      for 10 listeners with bilateral CIs and 8 listeners with HP CIs were taken from
      Loiselle, Dorman, Yost, Cook, and Gifford (2016), who used the same test
      protocol. Results: The use of the beamformer resulted in a 31 percentage point
      improvement in performance; in bilateral CIs, an 18 percentage point improvement;
      and in HP CIs, a 20 percentage point improvement. Conclusion: A monaural adaptive
      beamformer can produce an improvement in speech understanding in a complex noise
      environment that is equal to, or greater than, the improvement produced by
      bilateral CIs and HP surgery.

PMID- 28768326
TI  - The Importance of a Valid Comparison Group.

PMID- 28768325
TI  - Estimating Risk of Postsurgical General and Geriatric Complications Using the
      VESPA Preoperative Tool.
AB  - Importance: As greater numbers of older patients seek elective surgery, one
      approach to preventing postoperative complications is enhanced assessment of
      risks during preoperative evaluation. Objective: To determine whether a geriatric
      assessment tool can be implemented in a preoperative clinic and can estimate risk
      of postoperative complications. Design, Setting, and Participants: In this
      prospective cohort study, patients 70 years of age or older were assessed in a
      preoperative clinic for elective surgery from July 9, 2008, to January 5, 2011.
      Patients were screened using the Vulnerable Elders Surgical Pathways and Outcomes
      Assessment (VESPA) tool developed for this study. Patients were assessed on 5
      preoperative activities of daily living recommended by the American College of
      Surgeons (bathing, transferring, dressing, shopping, and meals), history of
      falling or gait impairment, and depressive symptoms (2-item Patient Health
      Questionnaire). Patients also underwent a brief cognitive examination (Mini-Cog)
      and gait and balance assessment (Timed Up and Go test). A novel question was also
      asked as to whether patients expected they could manage themselves alone after
      discharge. Comorbidities and work-related relative value units (categorized into
      low, moderate, and high tertiles) were also collected. Multivariable logistic
      regression was performed to estimate risk of postoperative complications.
      Sustainability of VESPA over time was also evaluated. Medical record review was
      performed from December 11, 2012, to October 2, 2015, and data analysis was
      performed from November 15, 2015, to May 18, 2016. Main Outcomes and Measures:
      Postoperative surgical and geriatric complications. Results: Of the 770 patients
      evaluated, 736 (384 women and 352 men; mean [SD] age, 77.7 [5.7] years) underwent
      740 operative procedures; of these patients, 711 had complete data for
      multivariable analysis. In our sample, 105 patients (14.3%) reported 1 or more
      difficulties with the 5 activities of daily living, and 270 of 707 patients
      (38.2%) foresaw themselves unable to manage self-care alone. A total of 131 of
      740 patients had geriatric complications, and 114 of 740 patients had surgical
      complications; 187 of 740 patients (25.3%) had either geriatric or surgical
      complications. On multivariable analysis, the number of difficulties with
      activities of daily living (odds ratio [OR], 1.3; 95% CI, 1.0-1.6), anticipated
      difficulty with postoperative self-care (OR, 1.6; 95% CI, 1.0-2.2), Charlson
      Comorbidity score of 2 or more vs less than 2 (OR, 1.5; 95% CI, 1.0-2.3), male
      sex (OR, 1.6; 95% CI, 1.1-2.3), and work-related relative value units (moderate
      vs low: OR, 1.9; 95% CI, 1.1-3.3; high vs low: OR, 8.8; 95% CI, 5.3-14.5) were
      independently associated with postoperative complications (overall model area
      under the receiver operating characteristic curve, 0.77). With these results, a
      whole-point VESPA score used alone to estimate risk of complications also
      demonstrated excellent fit (area under the curve, 0.76). Conclusions and
      Relevance: Preoperative assessment of older geriatric patients is feasible in the
      general preoperative clinic and can help identify patients at higher risk of
      postoperative complications.

PMID- 28768327
TI  - The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders
      Compared With Diagnosis-Specific Protocols for Anxiety Disorders: A Randomized
      Clinical Trial.
AB  - Importance: Transdiagnostic interventions have been developed to address barriers
      to the dissemination of evidence-based psychological treatments, but only a few
      preliminary studies have compared these approaches with existing evidence-based
      psychological treatments. Objective: To determine whether the Unified Protocol
      for Transdiagnostic Treatment of Emotional Disorders (UP) is at least as
      efficacious as single-disorder protocols (SDPs) in the treatment of anxiety
      disorders. Design, Setting, and Participants: From June 23, 2011, to March 5,
      2015, a total of 223 patients at an outpatient treatment center with a principal
      diagnosis of panic disorder with or without agoraphobia, generalized anxiety
      disorder, obsessive-compulsive disorder, or social anxiety disorder were randomly
      assigned by principal diagnosis to the UP, an SDP, or a waitlist control
      condition. Patients received up to 16 sessions of the UP or an SDP for 16 to 21
      weeks. Outcomes were assessed at baseline, after treatment, and at 6-month follow
      up. Analysis in this equivalence trial was based on intention to treat.
      Interventions: The UP or SDPs. Main Outcomes and Measures: Blinded evaluations of
      principal diagnosis clinical severity rating were used to evaluate an a priori
      hypothesis of equivalence between the UP and SDPs. Results: Among the 223
      patients (124 women and 99 men; mean [SD] age, 31.1 [11.0] years), 88 were
      randomized to receive the UP, 91 to receive an SDP, and 44 to the waitlist
      control condition. Patients were more likely to complete treatment with the UP
      than with SDPs (odds ratio, 3.11; 95% CI, 1.44-6.74). Both the UP (Cohen d, 
      0.93; 95% CI, -1.29 to -0.57) and SDPs (Cohen d, -1.08; 95% CI, -1.43 to -0.73)
      were superior to the waitlist control condition at acute outcome. Reductions in
      clinical severity rating from baseline to the end of treatment (beta, 0.25; 95%
      CI, -0.26 to 0.75) and from baseline to the 6-month follow-up (beta, 0.16; 95%
      CI, -0.39 to 0.70) indicated statistical equivalence between the UP and SDPs.
      Conclusions and Relevance: The UP produces symptom reduction equivalent to
      criterion standard evidence-based psychological treatments for anxiety disorders
      with less attrition. Thus, it may be possible to use 1 protocol instead of
      multiple SDPs to more efficiently treat the most commonly occurring anxiety and
      depressive disorders. Trial Registration: clinicaltrials.gov Identifier:
      NCT01243606.

PMID- 28768328
TI  - Prescription Opioid Analgesics Commonly Unused After Surgery: A Systematic
      Review.
AB  - Importance: Prescription opioid analgesics play an important role in the
      treatment of postoperative pain; however, unused opioids may be diverted for
      nonmedical use and contribute to opioid-related injuries and deaths. Objective:
      To quantify how commonly postoperative prescription opioids are unused, why they
      remain unused, and what practices are followed regarding their storage and
      disposal. Evidence Review: MEDLINE, EMBASE, and Cochrane Central Register of
      Controlled Trials were searched from database inception to October 18, 2016, for
      studies describing opioid oversupply for adults after a surgical procedure. The
      primary outcome-opioid oversupply-was defined as the number of patients with
      either filled but unused opioid prescriptions or unfilled opioid prescriptions.
      Two reviewers independently screened studies for inclusion, extracted data, and
      assessed the study quality. Findings: Six eligible studies reported on a total of
      810 unique patients (range, 30-250 patients) who underwent 7 different types of
      surgical procedures. Across the 6 studies, 67% to 92% of patients reported unused
      opioids. Of all the opioid tablets obtained by surgical patients, 42% to 71% went
      unused. Most patients stopped or used no opioids owing to adequate pain control,
      and 16% to 29% of patients reported opioid-induced adverse effects. In 2 studies
      examining storage safety, 73% to 77% of patients reported that their prescription
      opioids were not stored in locked containers. All studies reported low rates of
      anticipated or actual disposal, but no study reported US Food and Drug
      Administration-recommended disposal methods in more than 9% of patients.
      Conclusions and Relevance: Postoperative prescription opioids often go unused,
      unlocked, and undisposed, suggesting an important reservoir of opioids
      contributing to nonmedical use of these products, which could cause injuries or
      even deaths.

PMID- 28768332
TI  - Defining Potential Use of Nonstatin Therapies to Lower Blood Cholesterol Levels.

PMID- 28768329
TI  - National Readmission Patterns of Isolated Splenic Injuries Based on Initial
      Management Strategy.
AB  - Importance: Options for managing splenic injuries have evolved with a focus on
      nonoperative management. Long-term outcomes, such as readmissions and delayed
      splenectomy rate, are not well understood. Objective: To describe the natural
      history of isolated splenic injuries in the United States and determine whether
      patterns of readmission were influenced by management strategy. Design, Setting,
      and Participants: The Healthcare Cost and Utilization Project's Nationwide
      Readmission Database is an all-payer, all-ages, longitudinal administrative
      database that provides data on more than 35 million weighted US discharges
      yearly. The database was used to identify patients with isolated splenic injuries
      and the procedures that they received. Adult patients with isolated splenic
      injuries admitted from January 1 through June 30, 2013, and from January 1
      through June 30, 2014, were included. Those who died during the index
      hospitalization or who had an additional nonsplenic injury with an Abbreviated
      Injury Score of 2 or greater were excluded. Univariate and mixed-effects logistic
      regression analysis controlling for center effect were used. Weighted numbers are
      reported. Exposures: Initial management strategy at the time of index
      hospitalization, including nonprocedural management, angioembolization, and
      splenectomy. Main Outcomes and Measures: All-cause 6-month readmission rate.
      Secondary outcome was delayed splenectomy rate. Results: A weighted sample of
      3792 patients (2146 men [56.6%] and 1646 women [43.4%]; mean [SE] age, 48.5 [0.7]
      years) with 5155 admission events was included. During the index hospitalization,
      825 (21.8%) underwent splenectomy, 293 (7.7%) underwent angioembolization, and
      2673 (70.5%) had no procedure. The overall readmission rate was 21.1% (799
      patients). Readmission rates did not differ based on initial management strategy
      (195 patients undergoing splenectomy [23.6%], 70 undergoing angioembolism
      [23.9%], and 534 undergoing no procedure [20%]; P = .33). Splenectomy was
      performed in 36 of 799 readmitted patients (4.5%) who did not have a splenectomy
      at their index hospitalization, leading to an overall delayed splenectomy rate of
      1.2% (36 of 2967 patients). In mixed-effects logistic regression analysis
      controlling for patient, injury, clinical, and hospital characteristics, the
      choice of splenectomy (odds ratio, 0.93; 95% CI, 0.66-1.31) vs angioembolization
      (odds ratio, 1.19; 95% CI, 0.72-1.97) as initial management strategy was not
      associated with readmission. Conclusions and Relevance: This national evaluation
      of the natural history of isolated splenic injuries from index admission through
      6 months found that approximately 1 in 5 patients are readmitted within 6 months
      of discharge after an isolated splenic injury. However, the chance of readmission
      for splenectomy after initial nonoperative management was 1.2%. This finding
      suggests that the current management strategies used for isolated splenic
      injuries in the United States are well matched to patient need.

PMID- 28768333
TI  - Guidelines Update on Indications for Transcatheter Aortic Valve Replacement.

PMID- 28768334
TI  - Effect of Internet-Based Guided Self-help vs Individual Face-to-Face Treatment on
      Full or Subsyndromal Binge Eating Disorder in Overweight or Obese Patients: The
      INTERBED Randomized Clinical Trial.
AB  - Importance: Although cognitive behavioral therapy (CBT) represents the criterion
      standard for treatment of binge eating disorder (BED), most individuals do not
      have access to this specialized treatment. Objective: To evaluate the efficacy of
      internet-based guided self-help (GSH-I) compared with traditional, individual
      face-to-face CBT. Design, Setting, and Participants: The Internet and Binge
      Eating Disorder (INTERBED) study is a prospective, multicenter, randomized,
      noninferiority clinical trial (treatment duration, 4 months; follow-ups, 6 months
      and 1.5 years). A volunteer sample of 178 adult outpatients with full or
      subsyndromal BED were recruited from 7 university-based outpatient clinics from
      August 1, 2010, through December 31, 2011; final follow-up assessment was in
      April 2014. Data analysis was performed from November 30, 2014, to May 27, 2015.
      Interventions: Participants received 20 individual face-to-face CBT sessions of
      50 minutes each or sequentially completed 11 internet modules and had weekly
      email contacts. Main Outcomes and Measures: The primary outcome was the
      difference in the number of days with objective binge eating episodes (OBEs)
      during the previous 28 days between baseline and end of treatment. Secondary
      outcomes included OBEs at follow-ups, eating disorder and general
      psychopathologic findings, body mass index, and quality of life. Results: A total
      of 586 patients were screened, 178 were randomized, and 169 had at least one
      postbaseline assessment and constituted the modified intention-to-treat analysis
      group (mean [SD] age, 43.2 [12.3] years; 148 [87.6%] female); the 1.5-year follow
      up was available in 116 patients. The confirmatory analysis using the per
      protocol sample (n = 153) failed to show noninferiority of GSH-I (adjusted
      effect, 1.47; 95% CI, -0.01 to 2.91; P = .05). Using the modified intention-to
      treat sample, GSH-I was inferior to CBT in reducing OBE days at the end of
      treatment (adjusted effect, 1.63; 95% CI, 0.17-3.05; P = .03). Exploratory
      longitudinal analyses also showed the superiority of CBT over GSH-I by the 6
      month (adjusted effect, 0.36; 95% CI, 0.23-0.55; P < .001) but not the 1.5-year
      follow-up (adjusted effect, 0.91; 95% CI, 0.54-1.50; P = .70). Reductions in
      eating disorder psychopathologic findings were significantly higher in the CBT
      group than in the GSH-I group at 6-month follow-up (adjusted effect, -0.4; 95%
      CI, -0.68 to -0.13; P = .005). No group differences were found for body mass
      index, general psychopathologic findings, and quality of life. Conclusions and
      Relevance: Face-to-face CBT leads to quicker and greater reductions in the number
      of OBE days, abstinence rates, and eating disorder psychopathologic findings and
      may be a better initial treatment option than GSH-I. Internet-based guided self
      help remains a viable, slower-acting, low-threshold treatment alternative
      compared with CBT for adults with BED. Trial Registration: isrctn.org Identifier:
      ISRCTN40484777 and germanctr.de Identifier: DRKS00000409.

PMID- 28768335
TI  - Simulation of Lipid-Lowering Therapy Intensification in a Population With
      Atherosclerotic Cardiovascular Disease.
AB  - Importance: In patients with atherosclerotic cardiovascular disease (ASCVD),
      guidelines recommend optimizing statin treatment, and consensus pathways suggest
      use of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9)
      inhibitors in patients with persistently elevated low-density lipoprotein
      cholesterol (LDL-C) levels despite use of statins. Recent trials have provided
      evidence of benefit in reduction of cardiovascular events with these agents.
      Objective: To estimate the percentage of patients with ASCVD who would require a
      PCSK9 inhibitor when oral lipid-lowering therapy (LLT) is intensified first.
      Design, Setting, and Participants: This simulation model study used a large
      administrative database of US medical and pharmacy claims to identify a cohort of
      105 269 patients with ASCVD enrolled from January 1, 2012, through December 31,
      2013, who met the inclusion criteria (database cohort). Patients were sampled
      with replacement (bootstrapping) to match the US epidemiologic distribution and
      entered into a Monte Carlo simulation (simulation cohort) that applied stepwise
      treatment intensification algorithms in those with LDL-C levels of at least 70
      mg/dL. All patients not initially receiving a statin were given atorvastatin, 20
      mg, and the following LLT intensification steps were applied: uptitration to
      atorvastatin, 80 mg; add-on ezetimibe therapy; add-on alirocumab therapy, 75 mg
      (a PCSK9 inhibitor); and uptitration to alirocumab, 150 mg. Sensitivity analyses
      included evolocumab as a PCSK9 inhibitor. Efficacy was estimated from published
      studies and incorporated patient-level variation. Data were analyzed from
      December 2015 to May 2017. Exposures: Treatment intensification strategies with
      LLT. Main Outcomes and Measures: Use of LLT among the population with ASCVD and
      distributions of LDL-C levels under various treatment intensification scenarios.
      Results: Inclusion criteria were met by 105 269 individuals in the database
      cohort (57.2% male and 42.8% female; mean [SD] age, 65.1 [12.1] years). In the
      simulation cohort (1 million patients; 54.8% male and 45.2% female; mean [SD]
      age, 66.4 [12.2] years), before treatment intensification, 51.5% used statin
      monotherapy and 1.7% used statins plus ezetimibe. Only 25.2% achieved an LDL-C
      level of less than 70 mg/dL. After treatment intensification, 99.3% could achieve
      an LDL-C level of less than 70 mg/dL, including 67.3% with statin monotherapy,
      18.7% with statins plus ezetimibe, and 14% with add-on PCSK9 inhibitor.
      Conclusions and Relevance: Large gaps exist between recommendations and current
      practice regarding LLT in the population with ASCVD. In our model that assumes no
      LLT intolerance and full adherence, intensification of oral LLT could achieve an
      LDL-C level of less than 70 mg/dL in most patients, with only a modest percentage
      requiring a PCSK9 inhibitor.

PMID- 28768336
TI  - Transdiagnostic Cognitive Behavioral Therapy and the Return of the Repressed.

PMID- 28768337
TI  - Acute Kidney Injury Impairs Postnatal Renal Adaptation and Increases Morbidity
      and Mortality in Very Low-Birth-Weight Infants.
AB  - OBJECTIVE: This study aims to estimate the impact of acute kidney injury (AKI) on
      postnatal renal adaptation, morbidity, and mortality in very low-birth-weight
      (VLBW) infants. DESIGN: We conducted a retrospective study of 457 VLBW infants
      admitted to a tertiary level neonatal intensive care unit (NICU) between July
      2009 and April 2015. We compared patient characteristics, risk factors, serum
      creatinine trends, and adverse outcomes in infants with and without AKI using
      multivariate logistic regression analysis. RESULTS: Incidence of AKI was 19.5%.
      On multivariate analysis, postnatal risk factors such as patent ductus arteriosus
      and vancomycin use were significantly associated with AKI. Infants with AKI had
      significantly higher mortality; 25/89 (28%) versus 15/368 (4%) (p < 0.001). Among
      survivors with AKI, bronchopulmonary dysplasia (BPD) was more prevalent (52.8 vs.
      23.9%, p < 0.001), serum creatinine remained elevated for a longer duration and
      median length of stay extended by 38 days. CONCLUSION: Presence of AKI was
      associated with impaired postnatal renal adaptation, BPD, significantly longer
      stay in the NICU and higher mortality.

PMID- 28768338
TI  - Combined Effects of Fatigue and Surface Instability on Jump Biomechanics in Elite
      Athletes.
AB  - The present study aimed to examine the effects of fatigue and surface instability
      on kinetic and kinematic jump performance measures. Ten female and 10 male elite
      volleyball players (18+/-2 years) performed repetitive vertical double-leg box
      jumps until failure. Pre and post fatigue, jump height/performance index, ground
      reaction force and knee flexion/valgus angles were assessed during drop and
      countermovement jumps on stable and unstable surfaces. Fatigue, surface
      condition, and sex resulted in significantly lower drop jump performance and
      ground reaction force (p<=0.031, 1.1<=d<=3.5). Additionally, drop jump knee
      flexion angles were significantly lower following fatigue (p=0.006, d=1.5). A
      significant fatigue*surface*sex interaction (p=0.020, d=1.2) revealed fatigue
      related decrements in drop jump peak knee flexion angles under unstable
      conditions and in men only. Knee valgus angles were higher on unstable compared
      to stable surfaces during drop jumps and in females compared to males during drop
      and countermovement jumps (p<=0.054, 1.0<=d<=1.1). Significant surface*sex
      interactions during countermovement jumps (p=0.002, d=1.9) indicated that knee
      valgus angles at onset of ground contact were significantly lower on unstable
      compared to stable surfaces in males but higher in females. Our findings revealed
      that fatigue and surface instability resulted in sex-specific knee motion
      strategies during jumping in elite volleyball players.

PMID- 28768339
TI  - Habitual Minimalist Shod Running Biomechanics and the Acute Response to Running
      Barefoot.
AB  - The aim of the study was to determine whether habitual minimalist shoe runners
      present with purported favorable running biomechanithat reduce running injury
      risk such as initial loading rate. Eighteen minimalist and 16 traditionally
      cushioned shod runners were assessed when running both in their preferred
      training shoe and barefoot. Ankle and knee joint kinetics and kinematics, initial
      rate of loading, and footstrike angle were measured. Sagittal ankle and knee
      joint stiffness were also calculated. Results of a two-factor ANOVA presented no
      group difference in initial rate of loading when participants were running either
      shod or barefoot; however, initial loading rate increased for both groups when
      running barefoot (p=0.008). Differences in footstrike angle were observed between
      groups when running shod, but not when barefoot (minimalist:8.71+/-8.99 vs.
      traditional: 17.32+/-11.48 degrees, p=0.002). Lower ankle joint stiffness was
      found in both groups when running barefoot (p=0.025). These findings illustrate
      that risk factors for injury potentially differ between the two groups. Shoe
      construction differences do change mechanical demands, however, once habituated
      to the demands of a given shoe condition, certain acute favorable or unfavorable
      responses may be moderated. The purported benefits of minimalist running shoes in
      mimicking habitual barefoot running is questioned, and risk of injury may not be
      attenuated.

PMID- 28768340
TI  - A Novel Two-Velocity Method for Elaborate Isokinetic Testing of Knee Extensors.
AB  - Single outcomes of standard isokinetic dynamometry tests do not discern between
      various muscle mechanical capacities. In this study, we aimed to (1) evaluate the
      shape and strength of the force-velocity relationship of knee extensors, as
      observed in isokinetic tests conducted at a wide range of angular velocities, and
      (2) explore the concurrent validity of a simple 2-velocity method. Thirteen
      physically active females were tested for both the peak and averaged knee
      extensor concentric force exerted at the angular velocities of 30 degrees -240
      degrees /s recorded in the 90 degrees -170 degrees  range of knee extension. The
      results revealed strong (0.960<R<0.998) linear force-velocity relationships that
      depict the maximum muscle force (i.e. the force-intercept), velocity (velocity
      intercept), and power (their product). Moreover, the line drawn through only the
      60 degrees  and 180 degrees /s data (the '2-velocity method') revealed a high
      level of agreement with the force-velocity relationship obtained (0.76<R<0.97;
      all power<0.001); while the force-intercept highly correlated (0.68<R<0.84; all
      power<=0.01) with the directly measured isometric force. The 2-velocity method
      could therefore be developed into a standard method for isokinetic testing of
      mechanical capacities of knee extensors and, if supported by further research,
      other muscles. This brief and fatigue-free testing procedure could discern
      between muscle force, velocity, and power-producing capacities.

PMID- 28768341
TI  - Prediction Model of Serum Lithium Concentrations.
AB  - INTRODUCTION: Therapeutic drug monitoring is necessary for lithium, but clinical
      application of several prediction strategies is still limited because of
      insufficient predictive accuracy. We herein proposed a suitable model, using
      creatinine clearance (CLcr)-based lithium clearance (Li-CL). METHODS: Patients
      receiving lithium provided the following information: serum lithium and
      creatinine concentrations, time of blood draw, dosing regimen, concomitant
      medications, and demographics. Li-CL was calculated as a daily dose per trough
      concentration for each subject, and the mean of Li-CL/CLcr was used to estimate
      Li-CL for another 30 subjects. Serum lithium concentrations at the time of
      sampling were estimated by 1-compartment model with Li-CL, fixed distribution
      volume (0.79 L/kg), and absorption rate (1.5/hour) in the 30 subjects. RESULTS:
      One hundred thirty-one samples from 82 subjects (44 men; mean+/-standard
      deviation age: 51.4+/-16.0 years; body weight: 64.6+/-13.8 kg; serum creatinine:
      0.78+/-0.20 mg/dL; dose of lithium: 680.2+/-289.1 mg/day) were used to develop
      the pharmacokinetic model. The mean+/-standard deviation (95% confidence
      interval) of absolute error was 0.13+/-0.09 (0.10-0.16) mEq/L. DISCUSSION: Serum
      concentrations of lithium can be predicted from oral dosage with high precision,
      using our prediction model.

PMID- 28768342
TI  - Correction: The Effects of Vitamin D Supplementation on Glucose Metabolism and
      Lipid Profiles in Patients with Gestational Diabetes: A Systematic Review and
      Meta-Analysis of Randomized Controlled Trials.

PMID- 28768343
TI  - Correction: Maternal High-Fat Diet During Pregnancy and Lactation has Opposite
      Effects on Gonadal Expression of Leptin and Leptin Receptor in Rat Dams and Their
      Offspring.

PMID- 28768344
TI  - Determining Bilateral Strength Imbalances in Youth Basketball Athletes.
AB  - The aims of this study were: 1) to compare the strongest (D) and weakest (ND)
      limbs in determining muscle strength asymmetry (MSA) ratios among various muscle
      strength qualities and 2) to determine the relationships among various muscle
      strength qualities. 17 youth male basketball athletes (age=17.5+/-0.8 years;
      height=187.1+/-9.4 cm; body mass=81.4+/-10.1 kg) participated in this study. Knee
      flexor and extensor strength at 60 degrees .s-1 was assessed for both limbs with
      the use of isokinetic dynamometry. Other tests involved single-leg hop (SLH),
      countermovement jump (CMJ) and isometric mid-thigh pull (IMTP). Statistically
      significant differences (p<0.05; d=0.40-0.98) were found between D and ND limbs
      for all strength measures. Imbalance ratio of the IMTP was significantly related
      to those of SLH (r=0.75, p=0.01) whereas no significant relationships between
      D:ND ratios were found from all other tests. Percentage agreements of MSA ranged
      from 64.7-88.2% between muscle strength qualities. The findings provide support
      for the use of field tests to detect lower-limb strength imbalances. Future
      research should examine the effect of different asymmetry thresholds on
      percentage agreements to diagnose MSA and determine its relationship to athletic
      performance.

PMID- 28768345
TI  - [Are 10,000 steps per day enough?]

PMID- 28768346
TI  - [Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances:
      Possibilities and Challenges].
AB  - Background Recently, scientific interest in the therapeutic potential of
      serotonergic and psilocybin hallucinogens (psychedelics) such as lysergic acid
      diethylamide (LSD) and entactogens like 3,4-methylendioxymethamphetamine (MDMA)
      within the framework of psychotherapy has resumed. The present article provides
      an overview on the current evidence on substance-assisted psychotherapy with
      these substances. Method A selective search was carried out in the PubMed and
      Cochrane Library including studies investigating the clinical use of serotonergic
      psychoactive substances since 2000. Results Studies were found investigating the
      following indications: alcohol (LSD and psilocybin) and tobacco addiction
      (psilocybin), anxiety and depression in patients suffering from life-threatening
      somatic illness (LSD and psilocybin), obsessive-compulsive disorder (OCD)
      (psilocybin), treatment-resistant major depression (psilocybin), and
      posttraumatic stress disorder (PTSD) (MDMA). Discussion Substance use disorders,
      PTSD and anxiety and depression in patients suffering from life-threatening
      somatic illness belong to the indications with the best evidence for substance
      assisted psychotherapy with serotonergic psychoactive agents. To date, studies
      indicate efficacy and relatively good tolerability. Further studies are needed to
      determine whether these substances may represent suitable and effective treatment
      options for some treatment-resistant psychiatric disorders in the future.

PMID- 28768347
TI  - [Trajectory analysis of participation in a sample of stroke patients in German
      neurological outpatient rehabilitation centres].
AB  - Objective We used a trajectory analysis to evaluate the course of participation
      in a sample of stroke patients in German neurological outpatient rehabilitation
      centres. Among other benefits, the method of trajectory analysis enables
      exploration of variables that influence the course of rehabilitation. Method In a
      multicentric observational study, patients at 17 outpatient neurorehabilitation
      centres were asked to fill in a questionnaire four times: at the time of
      admission to the rehabilitation center, on discharge and on month 4 and 12 post
      rehab. Additionally, clinical experts were asked to rate the patients' status at
      admission and discharge. Results and conclusions We obtained data on 364 stroke
      patients. There was deterioration in the social participation of 36 (9.9 %)
      patients, no change was observed in the participation of 173 (47.5 %) patients,
      and there was improvement in the participation of 155 (42.6 %) patients. 99
      patients among the 173 patients that did not show changes in participation had
      already started with good participation scores. This questions the need for
      rehabilitation for this group. According to the sociodemographic variables, we
      could show that only sex and income are important for the course of
      rehabilitation. Further research is necessary about context factors that
      influence trajectories.

PMID- 28768348
TI  - [Psychiatric Emergencies in the Preclinical Emergency Medicine Service in Ulm,
      Germany in 2000 and 2010, and Practical Consequences].
AB  - Background Psychiatric emergencies (PE) in preclinical emergency medical services
      are about 5 - 10 % of all emergencies and represent often a source of
      difficulties in handling for the non-psychiatric professional helpers that deal
      with them. Studies informing about quantitative and qualitative changes of PEs in
      preclinical emergency medicine in Germany are scarce. Methods Therefore, we
      conducted a retrospective cross-sectional study of PE in a preclinical emergency
      medical service based on the protocols of the emergency ambulance of the Section
      for Emergency Medicine at the University Hospital Ulm comparing the years 2000
      and 2010. Results We observed a significant increase of PEs from 8.8 % in the
      year 2000 (n = 285, from a total of n = 3227) to 10.3 % in 2010 (n = 454, from a
      total of n = 4425). In both years intoxications were the most common PE [2000: n
      = 116 (44.4 %); 2010: n = 171 (37.7 %)], followed by suicide-related behavior
      [2000: n = 59 (22.6 %); 2010: n = 78 (17.2 %)] and acute anxiety disorders [2000:
      n = 37 (13 %); 2010: n = 105 (23.1 %)]. The mentioned three conditions accounted
      for about 80 % of all PE. Most frequently PE occurred at the weekend and with the
      highest density in the evening and at night (18 - 24 h) in both years. Patients
      with PE were predominantly men, but the rate of women causing PE increased
      between 2000 and 2010. Discussion/Conclusion This study provides preliminary data
      on current trends in PEs in preclinical emergency medicine in Germany and has
      implications for improving the medical care provided.

PMID- 28768349
TI  - [Bilateral hippocampal primary CNS lymphoma: unusual differential diagnosis of
      rapid progressive dementia].
AB  - We report on a 63-year old man suffering from rapid progressive dementia due to
      bilateral hippocampal primary CNS lymphoma. Early diagnosis especially in
      secondary dementia is essential because of potentially treatable aetiologies with
      regression of cognitive and behaviour abnormalities. Characteristic imaging
      findings especially in inflammatory and neoplastic lesions affecting the
      hippocampal structures are discussed.

PMID- 28768350
TI  - [Deep brain stimulation in movement disorders: evidence and therapy standards].
AB  - The deep brain stimulation (DBS) in movement disorders is well established and in
      many aspects evidence-based procedure. The treatment indications are very
      heterogeneous and very specific in their course and therapy. The deep brain
      stimulation plays very important, but usually not the central role in this
      conditions. The success in the application of DBS is essentially associated with
      the correct, appropriate and timely indication of the therapy in the course of
      these diseases. Thanks to the good standardization of the DBS procedure and
      sufficient published data, the recommendations for indication, diagnosis and
      operative procedures can be generated. The following article attempts to
      summarize the most important decision-making criteria and current therapy
      standards in this fairly comprehensive subject and to present them in close
      proximity to practice.

PMID- 28768351
TI  - [Editor's Comment].

PMID- 28768352
TI  - ?

PMID- 28768353
TI  - ?

PMID- 28768354
TI  - ?

PMID- 28768355
TI  - [Placement of a tracheobronchial bifurcation stent for treatment of tumor-related
      tracheobronchial stenoses and fistulas].

PMID- 28768356
TI  - [Singultus - Diagnostic Workup and Therapy].
AB  - A hiccup is a reflex movement with diffusely distributed afferents and efferents
      in the thorax; its functional relevance is controversial. In its physiological
      form, it is mostly a minor complaint that stops spontaneously and rarely leads to
      medical consultation. However, prolonged agonizing hiccups represent serious
      deterioration of quality of life. Chronic hiccups by definition last for more
      than 48 h, with gastroesophageal reflux being the frequent underlying disease.
      Various other causes affect multiple organ systems, some with serious underlying
      diseases. A hiccup may be the only symptom at the first manifestation of some
      neurological disorders. In neuroimaging a lesion of the medulla oblongata is
      often seen. A NMO and an ischemic stroke with Wallenberg syndrome are 2
      frequently underlying neurological diseases, but other inflammatory and vascular
      diseases and tumors of the central nervous system may be present. No optimal
      evidencebased recommendations for diagnosis and management of chronic hiccups are
      available. The search for the underlying disease often requires an
      interdisciplinary approach by internists, neurologists, and otolaryngologists.
      Symptomatic treatment may be necessary even before diagnosis. Persistent hiccups,
      a common problem in oncological palliative care, are often challenging. Proton
      pump inhibitor or prokinetics are used for treating underlying gastroesophageal
      reflux and baclofen with or without gabapentin in other cases. Anticonvulsants,
      antipsychotics, antidepressants, and calcium channel blockers represent other
      alternative treatment possibilities. In therapy-refractory cases, invasive
      procedures such as the selective phrenic nerve block are available. More studies
      are needed to help deal with the diagnostic and therapeutic challenge that
      hiccups present for neurologists.

PMID- 28768357
TI  - ?

PMID- 28768358
TI  - [From the Expert's Office: What medical consultants should know about acoustics
      and noise measuring technique].

PMID- 28768359
TI  - [Laryngopharyngeal reflux disease (LPRD) in children].
AB  - LPRD in children is characterized by symptoms, clinical findings, and sequelae
      caused by the reflux of gastric acid, bile acid or refluxate containing pepsin
      beyond the esophagus. For diagnostic procedures and therapy of gastroesophageal
      reflux disease (GERD) in children and adults widely accepted guidelines have been
      established. However, diagnosis and therapy of LPRD in children remains a
      continuous issue of inter- and intradisciplinary discussions. Although both GERD
      and LPRD in children are reflux-induced diseases, these two entities are
      different in symptoms, cause, diagnostic procedures, and therapy. Thus, the terms
      GERD and LPRD are not eligible to be used as synonyms.Otorhinolaryngologists are
      becoming more and more involved in the management of children with suspicious
      LPRD. With flexible transnasal laryngopharyngoscopy being one of the most
      important diagnostic tools for LPRD detection, otorhinolaryngologists play an
      important role in the interdisciplinary diagnostic network of physicians treating
      children with suspected LPRD. The present article highlights age-dependent
      clinical symptoms, diagnostic tools, differential diagnoses, and adequate therapy
      for pediatric LPRD.

PMID- 28768360
TI  - ?

PMID- 28768361
TI  - ?

PMID- 28768362
TI  - Umbilical endometriosis: a potential encounter for general surgeons.

PMID- 28768363
TI  - Implementing entrustable professional activities: the yellow brick road towards
      competency-based training?
AB  - BACKGROUND: We describe implementation of competency-based postgraduate surgical
      training, using an entrustable professional activities (EPAs) programme. The
      programme aims to improve patient outcomes by optimizing supervision of surgical
      trainees, creating opportunities for additional teaching and feedback. The
      curriculum was designed to maximize feasibility for implementation within a
      colorectal surgical department. METHODS: The curriculum was developed using
      previously described methods by consensus between two consultants within the
      department. Seven EPAs were identified and described for each grade of trainee. A
      consultant within the teaching faculty or a delegate is required to assess each
      EPA and provide formal feedback until the trainee is given permission to act
      autonomously. RESULTS: It is hoped the programme can progress with minimal
      disruption to key stakeholders. We will record trainee assessment data
      anticipating that performance of trainees on other tasks in the future may
      provide some evidence of validity for the EPA assessments. CONCLUSIONS: There are
      perceived benefits and problems evident in the EPA model at this early stage of
      implementation. The programme should result in an increase in the number of
      formative assessments and feedback opportunities for trainees. The assessment
      process is familiar to supervisors, which should facilitate implementation of the
      curriculum. There is concern that supervisors may require further training to
      ensure the assessment process is objective and reproducible. The EPA programme
      could make the process of delegating patient care to trainees more transparent,
      but we have not identified a method of widely disseminating trainee assessment
      data without the potential to prejudice trainees unfairly.

PMID- 28768364
TI  - General surgery primary operator rates: a guide to achieving future competency.
AB  - BACKGROUND: Competency in surgical training is a topic of much recent discussion,
      with concern regarding the adequacy of current training schemes to achieve
      competency. Most programmes use caseload and primary operator rates to assess
      trainee progression. Some trainees still lack technical competence even when
      recommended procedural numbers are met. It is possible that current measures of
      individual's capabilities used in surgical education are outdated. METHODS:
      Logbook data of New South Wales general surgical trainees between 2010 and 2012
      was obtained through General Surgeons Australia. The top 10 most common
      operations recorded in trainee logbooks were identified. Individual trainee data
      were grouped by the surgical education and training year and primary operator
      versus assistant experience. The data were analysed focusing on the primary
      operator rate, comparing between trainee levels to identify progression. RESULTS:
      A total of 183 319 operations were recorded in New South Wales general surgery
      trainee logbooks. A positive association was demonstrated between trainee
      seniority and primary operator rates for the most common procedures, indicating
      trainee's continual progression in experience as they advance. However,
      laparoscopic inguinal hernia repair, oversew of gastroduodenal ulcer, open
      cholecystectomy and right hemicolectomy showed poor primary operator rates among
      trainees regardless of trainee year, despite these operations being among the 10
      most common. CONCLUSION: General surgical trainees accumulate operative
      experience with progression through the surgical education and training
      programme, highlighting expected technical progression and competency of trainees
      for common procedures. For less common or more complicated procedures, the use of
      entrustable professional activities and accompanying simulation training could be
      used to achieve the necessary technical expertise.

PMID- 28768365
TI  - Importance of preoperative diagnosis for management of patients with suspected
      retroperitoneal sarcoma.
AB  - Soft tissue sarcoma is an umbrella term which encompasses over 60 histological
      tumour types. Approximately 15% of soft tissue sarcomas arise in the
      retroperitoneum. This complex group of tumours poses unique management challenges
      due to their often large size, histological heterogeneity and complexity of
      anatomical relationships. This review discusses the management of retroperitoneal
      tumours including the need for preoperative diagnosis, the evidence for
      neoadjuvant radiotherapy, the role of multivisceral resection and the importance
      of a multidisciplinary team approach.

PMID- 28768366
TI  - Semi-Automatic Electronic Stent Register: a novel approach to preventing ureteric
      stents lost to follow up.
AB  - BACKGROUND: Ureteric stents are indispensable tools in modern urology; however,
      the risk of them not being followed-up once inserted poses medical and medico
      legal risks. Stent registers are a common solution to mitigate this risk;
      however, manual registers are logistically challenging, especially for busy
      units. METHODS: Western Sydney Local Health District developed a novel Semi
      Automatic Electronic Stent Register (SAESR) utilizing billing information to
      track stent insertions. To determine the utility of this system, an audit was
      conducted comparing the 6 months before the introduction of the register to the
      first 6 months of the register. RESULTS: In the first 6 months of the register,
      457 stents were inserted. At the time of writing, two of these are severely
      delayed for removal, representing a rate of 0.4%. In the 6 months immediately
      preceding the introduction of the register, 497 stents were inserted, and six
      were either missed completely or severely delayed in their removal, representing
      a rate of 1.2%. A non-inferiority analysis found this to be no worse than the
      results achieved before the introduction of the register. CONCLUSION: The SAESR
      allowed us to improve upon our better than expected rate of stents lost to follow
      up or severely delayed. We demonstrated non-inferiority in the rate of lost or
      severely delayed stents, and a number of other advantages including savings in
      personnel costs. The semi-automatic register represents an effective way of
      reducing the risk associated with a common urological procedure. We believe that
      this methodology could be implemented elsewhere.

PMID- 28768367
TI  - Gastrointestinal: Mirizzi syndrome masquerading as primary cholangiocarcinoma.

PMID- 28768368
TI  - Triple site intussusceptions in Peutz-Jeghers syndrome.

PMID- 28768369
TI  - Recent developments in understanding the role of the gut microbiota in brain
      health and disease.
AB  - There is a growing appreciation of the role of the gut microbiota in all aspects
      of health and disease, including brain health. Indeed, roles for the bacterial
      commensals in various psychiatric and neurological conditions, such as
      depression, autism, stroke, Parkinson's disease, and Alzheimer's disease, are
      emerging. Microbiota dysregulation has been documented in all of these conditions
      or in animal models thereof. Moreover, depletion or modulation of the gut
      microbiota can affect the severity of the central pathology or behavioral
      deficits observed in a variety of brain disorders. However, the mechanisms
      underlying such effects are only slowly being unraveled. Additionally, recent
      preclinical and clinical evidence suggest that targeting the microbiota through
      prebiotic, probiotic, or dietary interventions may be an effective "psychobiotic"
      strategy for treating symptoms in mood, neurodevelopmental disorders, and
      neurodegenerative diseases.

PMID- 28768370
TI  - Efficacy and safety of nortriptyline in functional dyspepsia in Asians: A
      randomized double-blind placebo-controlled trial.
AB  - BACKGROUND AND AIM: Current treatments of functional dyspepsia (FD) are
      unsatisfied. Tricyclic antidepressants alter visceral hypersensitivity and brain
      gut interaction. We assessed the efficacy and safety of nortriptyline in patients
      with FD. METHODS: Patients diagnosed with FD according to Rome III criteria who
      failed to respond to proton pump inhibitor and prokinetic treatment were randomly
      assigned to either once daily 10-mg nortriptyline or placebo. The primary
      endpoint was the rate of responders defined as > 50% reduction in dyspepsia
      symptom score after 8 weeks of treatment. The secondary endpoints were
      improvement in quality of life as assessed by 36-Item Short Form Health Survey
      score and safety. RESULTS: Sixty-one patients (nortriptyline 28 and placebo 33)
      were enrolled. Dyspepsia symptom score and duration of symptoms were balanced at
      entry between both groups. Eight and seven patients in nortriptyline and placebo
      groups were lost to follow up. Seven patients withdrew due to mild adverse events
      (nortriptyline 1 and placebo 6). Overall, 19 with nortriptyline and 20 with
      placebo completed the study. Patients receiving nortriptyline did not achieve
      higher response rate than those in placebo in both intention-to-treat (53.6% vs
      57.6%, P = 0.75) and per-protocol (76.5% vs 73.7%, P = 1.00) analyses.
      Nortriptyline did not provide improvement in quality of life. The mean difference
      was 3.8 (P = 0.36) and 0.88 (P = 0.86) by intention-to-treat and 2.9 (P = 0.57)
      and 3.5 (P = 0.57) by per-protocol analyses in physical and mental component,
      respectively. All adverse events were minor and similar in both groups.
      CONCLUSION: Nortriptyline was not superior to placebo in management of patients
      with FD.

PMID- 28768371
TI  - Minimal hepatic encephalopathy identifies patients at risk of faster cirrhosis
      progression.
AB  - BACKGROUND AND AIM: Minimal hepatic encephalopathy (MHE) predicts poor prognosis
      and could reflect an advanced liver disease. We aimed to assess whether MHE could
      be a surrogate marker of a further liver disease. METHODS: Prospective
      multicenter study including 320 cirrhotic patients, followed for up to 5 years,
      which were classified at baseline in compensated cirrhosis without (stage 1) and
      with varices (stage 2), one decompensating event (stage 3), and any second
      decompensating event (stage 4). Cirrhosis progression was defined by a transition
      towards a different stage (competing events: liver transplant due to
      hepatocellular carcinoma and non-liver-related death). MHE was detected by
      critical flicker frequency and psychometric tests. RESULTS: Minimal hepatic
      encephalopathy was diagnosed in 18.2% (57/314) of patients. Cirrhosis progression
      occurred in 38.1% (122/320) of patients, while liver transplant was required in
      10.9% (35/320), and 19.1% (61/320) died. In competing risk regression, MHE was
      associated with disease progression: model 1 {subhazard ratio [sHR] 2.34
      [95%confidence interval (CI) 1.58-3.46]; P = 0.0001}; model 2 [sHR 2.18 (95%CI
      1.43-3.33); P = 0.0001]; model 3 [sHR 2.48 (95%CI 1.63-3.76); P = 0.0001]. The
      annual incidence rate of progression was higher in MHE patients: stage 1 (19.4 vs
      5.6 cases per 100 person-years); stage 2 (26.8 vs 15.6); stage 3 (45.7 vs 16.5);
      and stage 4 (40.7 vs 12.8). MHE showed a higher cumulative incidence of disease
      progression from the first year in decompensated and the third year in
      compensated cirrhosis. CONCLUSION: Minimal hepatic encephalopathy was associated
      with cirrhosis progression and showed a higher cumulative and annual incidence
      rate of disease progression. MHE could be a surrogate marker of disease
      progression, irrespective of cirrhosis status, identifying patients at risk of
      suffering a more aggressive cirrhosis form.

PMID- 28768372
TI  - Gastrointestinal: Gastric inflammatory fibroid polyp that was resected after a 10
      year follow-up.

PMID- 28768373
TI  - Editorial Comment to Predictors of operative time during radical retropubic
      prostatectomy and robot-assisted laparoscopic prostatectomy.

PMID- 28768375
TI  - Response to Editorial Comment to Predictors of operative time during radical
      retropubic prostatectomy and robot-assisted laparoscopic prostatectomy.

PMID- 28768376
TI  - Outcomes following open aortic surgery in the endovascular era.

PMID- 28768377
TI  - Response to Re: The Australasian contribution to the development of neurosurgery
      in Singapore.

PMID- 28768378
TI  - Re-expansion pulmonary oedema: an unusual and unsettling complication.

PMID- 28768379
TI  - Re: Single-stage laparoscopic cholecystectomy and intraoperative endoscopic
      retrograde cholangiopancreatography: is this strategy feasible in Australia?

PMID- 28768380
TI  - Re: Rare differential of right iliac fossa pain.

PMID- 28768381
TI  - Plastic surgery ward round: can we do better?

PMID- 28768382
TI  - Medicine in small doses.

PMID- 28768383
TI  - Porocarcinoma: a rare cutaneous lesion.

PMID- 28768384
TI  - The Garnett Passe and Rodney Williams Memorial Foundation: 25 years on.

PMID- 28768386
TI  - Improving clinical teaching for busy clinicians: integration of the one-minute
      preceptor into mini-clinical examination.

PMID- 28768387
TI  - General surgery's game changer and the unanswered question.

PMID- 28768388
TI  - Renaming a section of the journal: Professional Skills for Surgeons.

PMID- 28768389
TI  - Long-term diving-related lung damage: An editorial perspective.

PMID- 28768390
TI  - Rapid analysis of hyperbaric oxygen therapy registry data for reimbursement
      purposes: Technical communication.
AB  - OBJECTIVE: To explain how Hyperbaric Oxygen Therapy Registry (HBOTR) data of the
      US Wound Registry (USWR) helped establish a fair analysis of the physician work
      of hyperbaric chamber supervision for reimbursement purposes. METHODS: We queried
      HBOTR data from January 1, 2013, to December 31, 2013, on patient comorbidities
      and medications as well as the number of hyperbaric oxygen (HBO2) therapy
      treatments supervised per physician per day from all hyperbaric facilities
      participating in the USWR that had been using the electronic medical record (EHR)
      for more than six months and had passed data completeness checks. RESULTS: Among
      11,240 patients at the 87 facilities included, the mean number of comorbidities
      and medications was 10 and 12, respectively. The mean number of HBO2 treatments
      supervised per physician per day was 3.7 at monoplace facilities and 5.4 at
      multiplace facilities. Following analysis of these data by the RUC, the
      reimbursement rate of chamber supervision was decreased to $112.06. CONCLUSIONS:
      Patients undergoing HBO2 therapy generally suffer from multiple, serious
      comorbidities and require multiple medications, which increase the risk of HBO2
      and necessitate the presence of a properly trained hyperbaric physician. The lack
      of engagement by hyperbaric physicians in registry reporting may result in lack
      of adequate data being available to counter future challenges to reimbursement.

PMID- 28768391
TI  - The validity of transcutaneous oxygen measurements in predicting healing of
      diabetic foot ulcers.
AB  - INTRODUCTION: In 2002 Fife and Strauss (Fife, et al. Wound Rep Reg, 10:198-207;
      Strauss, et al. Foot Ankle Intl, 23:933-937) studied the predictability of
      transcutaneous oxygen measurements (TCOMs) for healing diabetic foot ulcers
      (DFUs). This paper analyzes the validity of the two studies and combines their
      information to predict which DFU will heal with adjunctive hyperbaric oxygen
      (HBO2) treatments. METHODS: A statistical review of the Fife and Strauss papers
      was performed. The numbers presented in the papers were subjected to analyses to
      compare like by like data as well as test for p-values and odds ratios for
      predicting healing of DFUs with HBO2. RESULTS: In the Strauss paper 143 subjects
      were studied in retrospective and prospective series. In those TCOMs which exceed
      200 mmHg with HBO2 healing occurred in 87.5% even if the room air TCOM was ? 30
      mmHg (p ? 0.001). The Fife paper studied retrospectively a subset of 221 patients
      who had TCOMs with HBO2. Failure rates for healing decreased progressively from
      35.7% to 14.3%, with TCOMs grouped in 100-mmHg increments from 200 mmHg to 699
      mmHg. This resulted in absence of statistical significance for any 100-mmHg range
      over 200 mmHg with HBO2 due to the small number of subjects for each 100-mmHg
      grouping. CONCLUSIONS: Although differences exist between the study designs, each
      complements the other. If TCOMs exceed 200 mmHg with HBO2, both authors observed
      that almost 90% of DFUs healed regardless of the room air readings when HBO2 was
      used as an adjunct to management.

PMID- 28768392
TI  - Pulmonary function changes in Navy divers during their professional careers.
AB  - INTRODUCTION: In divers, conflicting results regarding the development of small
      airway disease and "large lungs" have been reported. PURPOSE: To analyze the
      changes in pulmonary function over time, the development of "large lungs" and to
      see whether the pulmonary function deviates from subjects with "non-large lungs."
      METHODS: It is a longitudinal cohort study from 1983 till 2013 in professional
      navy divers, in which lung functions tests were performed annually. RESULTS: In
      1,260 navy divers, 8,149 pulmonary function tests were analyzed. The forced
      expiratory volume (FEV1) did not change except initially in those with abnormally
      low lung function (baseline value ?lower-limit-of-normal for the general
      population (LLN). In that group, FEV1 increased by 35 (SE 7) ml/year. For the
      entire cohort, the inspiratory vital capacity (iVC) increased by 73 ml/year (SE
      25). In the ?LLN cohort, it increased by an additional 40 ml/year (SE 18). For
      the entire cohort, the FEV1/iVC annual drop was 0.37% (SE 0.9), but in the ?LLN
      cohort it increased by 0.25%/year (SE 0.04). For the entire cohort, the forced
      expiratory flow at 75% of expiration (FEF75) annual drop was 23 ml/s/year (SE 7),
      in contrast in the ?LLN cohort it increased by an additional 45 ml/second/year
      (SE 7). Of the navy divers, 6.3% showed "large lungs," but changes over time were
      not different from above except for an additional 0.2% (SE 0.1%) decline in
      FEV1/iVC. CONCLUSIONS: In professional navy divers, long-term pulmonary function
      changes (FEV1 and FEV1 /iVC and FEF75) are not different from those in the non
      diving population. The iVC increases probably due to training effect.

PMID- 28768393
TI  - Abstracts from the UHMS 2016 Annual Scientific Meeting.

PMID- 28768394
TI  - The discussion on diabetic foot ulcer continues.

PMID- 28768395
TI  - Serious concerns about the Toronto Hyperbaric Oxygen for Diabetic Foot Ulcer
      study.

PMID- 28768396
TI  - Concerns regarding Fedorko, et al.'s article: Hyperbaric oxygen does not reduce
      indications.

PMID- 28768397
TI  - Immersion pulmonary edema - facts and fancies.

PMID- 28768398
TI  - Response to Dr. Davis' letter: Immersion pulmonary edema - facts and fancies.

PMID- 28768399
TI  - Immediate Endoscopic Management of an Intramural Hematoma Developed during
      Colonoscopy.

PMID- 28768400
TI  - Strategies for Appropriate Patient-centered Care to Decrease the Nationwide Cost
      of Cancers in Korea.
AB  - In terms of years of life lost to premature mortality, cancer imposes the highest
      burden in Korea. In order to reduce the burden of cancer, the Korean government
      has implemented cancer control programs aiming to reduce cancer incidence, to
      increase survival rates, and to decrease cancer mortality. However, these
      programs may paradoxically increase the cost burden. For examples, a cancer
      screening program for early detection could bring about over-diagnosis and over
      treatment, and supplying medical services in a paternalistic manner could lead to
      defensive medicine or futile care. As a practical measure to reduce the cost
      burden of cancer, appropriate cancer care should be established. Ensuring
      appropriateness requires patient-doctor communication to ensure that utility
      values are shared and that autonomous decisions are made regarding medical
      services. Thus, strategies for reducing the cost burden of cancer through
      ensuring appropriate patient-centered care include introducing value-based
      medicine, conducting cost-utility studies, and developing patient decision aids.

PMID- 28768401
TI  - Associations Between Preschool Education Experiences and Adulthood Self-rated
      Health.
AB  - OBJECTIVES: This study aimed to examine the association between preschool
      education experiences and adulthood self-rated health using representative data
      from a national population-based survey. METHODS: Data from the Korean Labor and
      Income Panel Study in 2006 and 2012 were used. A total of 2391 men and women 21
      41 years of age were analyzed. Log-binomial regression analyses were conducted to
      examine the associations between preschool education experience and self-rated
      health in adulthood. Parental socioeconomic position (SEP) indicators were
      considered as confounders of the association between preschool education
      experience and adulthood subjective health, while current SEP indicators were
      analyzed as mediators. Age-adjusted prevalence ratios (PRs) and the associated
      95% confidence intervals (CIs) were estimated. RESULTS: Compared with men without
      any experience of preschool education, those with both kindergarten and other
      preschool education experiences showed a lower prevalence of self-rated poor
      health (PR, 0.65; 95% CI, 0.47 to 0.89). In women, however, such an association
      was not evident. The relationship of preschool education experiences with self
      rated poor health in adulthood among men was confounded by parental SEP
      indicators and was also mediated by current SEP indicators. After adjustment for
      parental and current SEP indicators, the magnitude of the associations between
      preschool education experiences and adulthood subjective health was attenuated in
      men. CONCLUSIONS: Preschool education experience was associated with adulthood
      self-rated health in men. However, this association was explained by parental and
      current SEP indicators. Further investigations employing a larger sample size and
      objective health outcomes are warranted in the future.

PMID- 28768402
TI  - Factors Associated With Subjective Life Expectancy: Comparison With Actuarial
      Life Expectancy.
AB  - OBJECTIVES: Subjective life expectancy (SLE) has been found to show a significant
      association with mortality. In this study, we aimed to investigate the major
      factors affecting SLE. We also examined whether any differences existed between
      SLE and actuarial life expectancy (LE) in Korea. METHODS: A cross-sectional
      survey of 1000 individuals in Korea aged 20-59 was conducted. Participants were
      asked about SLE via a self-reported questionnaire. LE from the National Health
      Insurance database in Korea was used to evaluate differences between SLE and
      actuarial LE. Age-adjusted least-squares means, correlations, and regression
      analyses were used to test the relationship of SLE with four categories of
      predictors: demographic factors, socioeconomic factors, health behaviors, and
      psychosocial factors. RESULTS: Among the 1000 participants, women (mean SLE,
      83.43 years; 95% confidence interval, 82.41 to 84.46 years; 48% of the total
      sample) had an expected LE 1.59 years longer than that of men. The socioeconomic
      factors of household income and housing arrangements were related to SLE. Among
      the health behaviors, smoking status, alcohol status, and physical activity were
      associated with SLE. Among the psychosocial factors, stress, self-rated health,
      and social connectedness were related to SLE. SLE had a positive correlation with
      actuarial estimates (r=0.61, p<0.001). Gender, household income, history of
      smoking, and distress were related to the presence of a gap between SLE and
      actuarial LE. CONCLUSIONS: Demographic factors, socioeconomic factors, health
      behaviors, and psychosocial factors showed significant associations with SLE, in
      the expected directions. Further studies are needed to determine the reasons for
      these results.

PMID- 28768403
TI  - Assessing Health Impacts of Pictorial Health Warning Labels on Cigarette Packs in
      Korea Using DYNAMO-HIA.
AB  - OBJECTIVES: This study aimed to predict the 10-year impacts of the introduction
      of pictorial warning labels (PWLs) on cigarette packaging in 2016 in Korea for
      adults using DYNAMO-HIA. METHODS: In total, four scenarios were constructed to
      better understand the potential health impacts of PWLs: two for PWLs and the
      other two for a hypothetical cigarette tax increase. In both policies, an
      optimistic and a conservative scenario were constructed. The reference scenario
      assumed the 2015 smoking rate would remain the same. Demographic data and
      epidemiological data were obtained from various sources. Differences in the
      predicted smoking prevalence and prevalence, incidence, and mortality from
      diseases were compared between the reference scenario and the four policy
      scenarios. RESULTS: It was predicted that the optimistic PWLs scenario (PWO)
      would lower the smoking rate by 4.79% in males and 0.66% in females compared to
      the reference scenario in 2017. However, the impact on the reduction of the
      smoking rate was expected to diminish over time. PWO will prevent 85 238 cases of
      diabetes, 67 948 of chronic obstructive pulmonary disease, 31 526 of ischemic
      heart disease, 21 036 of lung cancer, and 3972 prevalent cases of oral cancer in
      total over the 10-year span due to the reductions in smoking prevalence. The
      impacts of PWO are expected to be between the impact of the optimistic and the
      conservative cigarette tax increase scenarios. The results were sensitive to the
      transition probability of smoking status. CONCLUSIONS: The introduction of PWLs
      in 2016 in Korea is expected reduce smoking prevalence and disease cases for the
      next 10 years, but regular replacements of PWLs are needed for persistent
      impacts.

PMID- 28768404
TI  - Can Obesity Cause Depression? A Pseudo-panel Analysis.
AB  - OBJECTIVES: The US ranks ninth in obesity in the world, and approximately 7% of
      US adults experience major depressive disorder. Social isolation due to the
      stigma attached to obesity might trigger depression. METHODS: This paper examined
      the impact of obesity on depression. To overcome the endogeneity problem, we
      constructed pseudopanel data using the Behavioral Risk Factor Surveillance System
      from 1997 to 2008. RESULTS: The results were robust, and body mass index (BMI)
      was found to have a positive effect on depression days and the percentage of
      depressed individuals in the population. CONCLUSIONS: We attempted to overcome
      the endogeneity problem by using a pseudo-panel approach and found that increases
      in the BMI increased depression days (or being depressed) to a statistically
      significant extent, with a large effect size.

PMID- 28768405
TI  - Knowledge and Perceptions of Influenza Vaccinations Among College Students in
      Vietnam and the United States.
AB  - OBJECTIVES: Influenza is a significant worldwide public health issue. Knowledge
      and perceptions regarding the flu vaccination are associated with whether
      individuals obtain the vaccination. The purpose of this study was to examine how
      such perceptions were related to knowledge and self-efficacy regarding influenza
      and the flu vaccination in Vietnam and the US. METHODS: College students (n=932)
      in Vietnam (n=495) and the US (n=437) completed a self-administered survey
      regarding knowledge and perceptions of influenza vaccinations in September and
      October 2016. RESULTS: Vietnamese participants reported significantly lower
      levels of awareness about flu risk, higher levels of negative attitudes toward
      flu vaccination, lower levels of knowledge about the flu and vaccination, and
      lower levels of self-efficacy than US participants. Higher levels of flu and flu
      vaccination knowledge and self-efficacy regarding general responsible health
      practices were associated with lower levels of negative perceptions of flu risk
      and attitudes toward vaccination. At the same time, self-efficacy regarding
      responsible health practices was associated with higher levels of awareness of
      flu risk and lower levels of negative attitudes toward vaccination. Self-efficacy
      regarding exercise was associated with lower levels of perceptions of flu risk
      and higher levels of negative attitudes toward vaccination. CONCLUSIONS: Vietnam
      could benefit from influenza education based on this comparison with the US. In
      both countries, knowledge and self-efficacy were found to be important factors
      influencing perceptions of influenza risk and vaccination.

PMID- 28768406
TI  - Community-acquired Legionnaires' Disease in a Newly Constructed Apartment
      Building.
AB  - OBJECTIVES: Legionnaires' disease (LD) is a severe type of pneumonia caused by
      inhalation of aerosols contaminated with Legionella. On September 22, 2016, a
      single case of LD was reported from a newly built apartment building in Gyeonggi
      province. This article describes an epidemiologic investigation of LD and
      identification of the possible source of infection. METHODS: To identify the
      source of LD, we interviewed the patient's husband using a questionnaire based on
      the Legionella management guidelines from the Korea Centers for Disease Control
      and Prevention. Water samples from the site were collected and analyzed. An
      epidemiological investigation of the residents and visitors in the apartment
      building was conducted for 14 days before the index patient's symptoms first
      appeared to 14 days after the implementation of environmental control measures.
      RESULTS: Legionella pneumophila serogroup 1 was isolated from the heated-water
      samples from the patient's residence and the basement of the apartment complex.
      Thirty-two suspected cases were reported from the apartment building during the
      surveillance period, yet all were confirmed negative based on urinary antigen
      tests. CONCLUSIONS: The likely source of infection was the building's potable
      water, particularly heated water. Further study of effective monitoring systems
      in heated potable water should be considered.

PMID- 28768408
TI  - What Controls Photocatalytic Water Oxidation on Rutile TiO2(110) under Ultra-High
      Vacuum Conditions?
AB  - The photocatalytic O-H dissociation of water absorbed on a rutile TiO2(110)
      surface in ultrahigh vacuum (UHV) is studied with spin-polarized density
      functional theory and a hybrid exchange-correlation functional (HSE06), treating
      the excited-state species as excitons with triplet multiplicity. This system is a
      model for the photocatalytic oxidation of water by TiO2 in an aqueous medium,
      which is relevant for the oxygen evolution reaction and photodegradation of
      organic pollutants. We provide a comprehensive mechanistic picture where the most
      representative paths correspond to excitonic configurations with the hole located
      on three- and two-coordinate surface oxygen atoms (O3s and O2s). Our picture
      explains the formation of the species observed experimentally. At near band gap
      excitation, the O3s path leads to the generation of hydroxyl anions which diffuse
      on the surface, without net oxidation. In contrast, free hydroxyl radicals are
      formed at supra band gap excitation (e.g., 266 nm) from an interfacial exciton
      that undergoes O-H dissociation. The oxidation efficiency is low because the path
      associated with the O2s exciton, which is the most favored one thermodynamically,
      is unreactive because of a high propensity for charge recombination. Our results
      are also relevant to understand the reactivity in the liquid phase. We assign the
      photoluminescence measured for atomically flat TiO2(110) surfaces in an aqueous
      medium to the O3s exciton, in line with the proposal based on experiments, and we
      have identified a species derived from the O2s exciton with an activated O2s-Ti
      bond that may be relevant in photocatalytic applications in an aqueous medium.

PMID- 28768407
TI  - The Big Vitamin D Mistake.
AB  - Since 2006, type 1 diabetes in Finland has plateaued and then decreased after the
      authorities' decision to fortify dietary milk products with cholecalciferol. The
      role of vitamin D in innate and adaptive immunity is critical. A statistical
      error in the estimation of the recommended dietary allowance (RDA) for vitamin D
      was recently discovered; in a correct analysis of the data used by the Institute
      of Medicine, it was found that 8895 IU/d was needed for 97.5% of individuals to
      achieve values >=50 nmol/L. Another study confirmed that 6201 IU/d was needed to
      achieve 75 nmol/L and 9122 IU/d was needed to reach 100 nmol/L. The largest meta
      analysis ever conducted of studies published between 1966 and 2013 showed that 25
      hydroxyvitamin D levels <75 nmol/L may be too low for safety and associated with
      higher all-cause mortality, demolishing the previously presumed U-shape curve of
      mortality associated with vitamin D levels. Since all-disease mortality is
      reduced to 1.0 with serum vitamin D levels >=100 nmol/L, we call public health
      authorities to consider designating as the RDA at least three-fourths of the
      levels proposed by the Endocrine Society Expert Committee as safe upper tolerable
      daily intake doses. This could lead to a recommendation of 1000 IU for children
      <1 year on enriched formula and 1500 IU for breastfed children older than 6
      months, 3000 IU for children >1 year of age, and around 8000 IU for young adults
      and thereafter. Actions are urgently needed to protect the global population from
      vitamin D deficiency.

PMID- 28768410
TI  - Synthesis, Characterization, and Activity of a Triazine Bridged Antioxidant Small
      Molecule.
AB  - Metal-ion misregulation and oxidative stress continue to be components of the
      continually evolving hypothesis describing the molecular origins of Alzheimer's
      disease. Therefore, these features are viable targets for synthetic chemists to
      explore through hybridizations of metal-binding ligands and antioxidant units. To
      date, the metal-binding unit in potential therapeutic small molecules has largely
      been inspired by clioquinol with the exception of a handful of heterocyclic small
      molecules and open-chain systems. Heterocyclic small molecules such as cyclen
      (1,4,7,10-tetraazacyclododecane) have the advantage of straightforward N-based
      modifications, allowing the addition of functional groups. In this work, we
      report the synthesis of a triazine bridged system containing two cyclen metal
      binding units and an antioxidant coumarin appendage inspired by nature. This new
      potential therapeutic molecule shows the ability to bind copper in a unique
      manner compared to other chelates proposed to treat Alzheimer's disease. DPPH and
      TEAC assays exploring the activity of N-(2-((4,6-di(1,4,7,10-tetraazacyclododecan
      1-yl)-1,3,5-triazin-2-yl)amino)ethyl)-2-oxo-2H-chromene-3-carboxamide (molecule
      1) show that the molecule is antioxidant. Cellular studies of molecule 1 indicate
      a low toxicity (EC50 = 80 MUM) and the ability to protect HT-22 neuronal cells
      from cell death induced by Abeta + copper(II), thus demonstrating the potential
      for molecule 1 to serve as a multimodal therapeutic for Alzheimer's disease.

PMID- 28768411
TI  - Larval Red Drum (Sciaenops ocellatus) Sublethal Exposure to Weathered Deepwater
      Horizon Crude Oil: Developmental and Transcriptomic Consequences.
AB  - The Deepwater Horizon (DWH) incident resulted in extensive oiling of the pelagic
      zone and shoreline habitats of many commercially important fish species. Exposure
      to the water-accommodated fraction (WAF) of oil from the spill causes
      developmental toxicity through cardiac defects in pelagic fish species. However,
      few studies have evaluated the effects of the oil on near-shore estuarine fish
      species such as red drum (Sciaenops ocellatus). Following exposure to a certified
      weathered slick oil (4.74 MUg/L ?PAH50) from the DWH event, significant sublethal
      impacts were observed ranging from impaired nervous system development [average
      17 and 22% reductions in brain and eye area at 48 h postfertilization (hpf),
      respectively] to abnormal cardiac morphology (100% incidence at 24, 48, and 72
      hpf) in red drum larvae. Consistent with the phenotypic responses, significantly
      differentially expressed transcripts, enriched gene ontology, and altered
      functions and canonical pathways predicted adverse outcomes in nervous and
      cardiovascular systems, with more pronounced changes at later larval stages. Our
      study demonstrated that the WAF of weathered slick oil of DWH caused
      morphological abnormalities predicted by a suite of advanced bioinformatic tools
      in early developing red drum and also provided the basis for a better
      understanding of molecular mechanisms of crude oil toxicity in fish.

PMID- 28768409
TI  - Opiates and Plasticity in the Ventral Tegmental Area.
AB  - Opioids are among the most effective pain relievers; however, their abuse has
      been on the rise worldwide evident from an alarming increase in accidental opioid
      overdoses. This demands for an urgent increase in scientific endeavors for better
      understanding of main cellular mechanisms and circuits involved in opiate
      addiction. Preclinical studies strongly suggest that memories associated with
      positive and negative opioid experiences are critical in promoting compulsive
      opiate-seeking and opiate-taking behaviors, and relapse. Particular focus on
      synaptic plasticity as the cellular correlate of learning and memory has rapidly
      evolved in drug addiction field over the past two decades. Several critical
      addiction-related brain areas are identified, one of which is the ventral
      tegmental area (VTA), an area intensively studied as the initial locus for drug
      reward. Here, we provide an update to our previous review on "Opiates and
      Plasticity" highlighting the most recent discoveries of synaptic plasticity
      associated with opiates in the VTA. Electrophysiological studies of plasticity of
      addiction to date have been invaluable in addressing learning processes and
      mechanisms that underlie motivated and addictive behaviors, and now with the
      availability of powerful technologies of transgenic approaches and optogenetics,
      circuit-based studies hold high promise in fostering synaptic studies of opiate
      addiction.

PMID- 28768412
TI  - Receptor Targeted Polymeric Nanostructures Capable of Navigating across the Blood
      Brain Barrier for Effective Delivery of Neural Therapeutics.
AB  - The window of neurological maladies encompasses 600 known neurological disorders.
      In the past few years, an inordinate upsurge in the incidences of neuronal
      ailments with increased mortality rate has been witnessed globally. Despite
      noteworthy research in the discovery and development of neural therapeutics,
      brain drug delivery still encounters limited success due to meager perviousness
      of most of the drug molecules through the blood-brain barrier (BBB), a tight
      layer of endothelial cells that selectively impedes routing of the molecules
      across itself. In this Review, we have tried to present a comprehensive idea on
      the recent developments in nanoparticle based BBB delivery systems, with a focus
      on the advancements in receptor targeted polymeric nanoparticles pertaining to
      BBB delivery. We have also attempted to bridge the gap between conventional brain
      delivery strategies and nanoparticle based BBB delivery for in-depth
      understanding. Various strategies are being explored for simplifying delivery of
      molecules across the BBB; however, they have their own limitations such as
      invasiveness and need for hospitalization and surgery. Introduction of
      nanotechnology can impressively benefit brain drug delivery. Though many
      nanoparticles are being explored, there are still several issues that need to be
      analyzed scrupulously before a real and efficient BBB traversing nanoformulation
      is realized.

PMID- 28768413
TI  - Monovalent Cation Activation of the Radical SAM Enzyme Pyruvate Formate-Lyase
      Activating Enzyme.
AB  - Pyruvate formate-lyase activating enzyme (PFL-AE) is a radical S-adenosyl-l
      methionine (SAM) enzyme that installs a catalytically essential glycyl radical on
      pyruvate formate-lyase. We show that PFL-AE binds a catalytically essential
      monovalent cation at its active site, yet another parallel with B12 enzymes, and
      we characterize this cation site by a combination of structural, biochemical, and
      spectroscopic approaches. Refinement of the PFL-AE crystal structure reveals Na+
      as the most likely ion present in the solved structures, and pulsed electron
      nuclear double resonance (ENDOR) demonstrates that the same cation site is
      occupied by 23Na in the solution state of the as-isolated enzyme. A SAM
      carboxylate-oxygen is an M+ ligand, and EPR and circular dichroism spectroscopies
      reveal that both the site occupancy and the identity of the cation perturb the
      electronic properties of the SAM-chelated iron-sulfur cluster. ENDOR studies of
      the PFL-AE/[13C-methyl]-SAM complex show that the target sulfonium positioning
      varies with the cation, while the observation of an isotropic hyperfine coupling
      to the cation by ENDOR measurements establishes its intimate, SAM-mediated
      interaction with the cluster. This monovalent cation site controls enzyme
      activity: (i) PFL-AE in the absence of any simple monovalent cations has little
      no activity; and (ii) among monocations, going down Group 1 of the periodic table
      from Li+ to Cs+, PFL-AE activity sharply maximizes at K+, with NH4+ closely
      matching the efficacy of K+. PFL-AE is thus a type I M+-activated enzyme whose M+
      controls reactivity by interactions with the cosubstrate, SAM, which is bound to
      the catalytic iron-sulfur cluster.

PMID- 28768415
TI  - Functionalization of Cadmium Selenide Quantum Dots with Poly(ethylene glycol):
      Ligand Exchange, Surface Coverage, and Dispersion Stability.
AB  - Semiconductor quantum dots synthesized using rapid mixing of precursors by
      injection into a hot solution of solvents and surfactants have surface ligands
      that sterically stabilize the dispersions in nonpolar solvents. Often, these
      ligands are exchanged to disperse the quantum dots in polar solvents, but
      quantitative studies of quantum dot surfaces before and after ligand exchange are
      scarce. We studied exchanging trioctylphosphine (TOP) and trioctylphosphine oxide
      (TOPO) ligands on as-synthesized CdSe quantum dots dispersed in hexane with a
      2000 g/mol thiolated poly(ethylene glycol) (PEG) polymer. Using infrared
      spectroscopy we quantify the absolute surface concentration of TOP/TOPO and PEG
      ligands per unit area before and after ligand exchange. While 50-85% of the
      TOP/TOPO ligands are removed upon ligand exchange, only a few are replaced with
      PEG. Surprisingly, the remaining TOP/TOPO ligands outnumber the PEG ligands, but
      these few PEG ligands are sufficient to disperse the quantum dots in polar
      solvents such as chloroform, tetrahydrofuran, and water. Moreover, as-synthesized
      quantum dots once easily dispersed in hexane are no longer dispersible in
      nonpolar solvents after ligand exchange. A subtle coverage-dependent balance
      between attractive PEG-solvent interactions and repulsive TOP/TOPO-solvent
      interactions determines the dispersion stability.

PMID- 28768414
TI  - Quantitative Temporal in Vivo Proteomics Deciphers the Transition of Virus-Driven
      Myeloid Cells into M2 Macrophages.
AB  - Myeloid cells play a central role in the context of viral eradication, yet
      precisely how these cells differentiate throughout the course of acute infections
      is poorly understood. In this study, we have developed a novel quantitative
      temporal in vivo proteomics (QTiPs) platform to capture proteomic signatures of
      temporally transitioning virus-driven myeloid cells directly in situ, thus taking
      into consideration host-virus interactions throughout the course of an infection.
      QTiPs, in combination with phenotypic, functional, and metabolic analyses,
      elucidated a pivotal role for inflammatory CD11b+, Ly6G-, Ly6Chigh-low cells in
      antiviral immune response and viral clearance. Most importantly, the time
      resolved QTiPs data set showed the transition of CD11b+, Ly6G-, Ly6Chigh-low
      cells into M2-like macrophages, which displayed increased antigen-presentation
      capacities and bioenergetic demands late in infection. We elucidated the pivotal
      role of myeloid cells in virus clearance and show how these cells phenotypically,
      functionally, and metabolically undergo a timely transition from inflammatory to
      M2-like macrophages in vivo. With respect to the growing appreciation for in vivo
      examination of viral-host interactions and for the role of myeloid cells, this
      study elucidates the use of quantitative proteomics to reveal the role and
      response of distinct immune cell populations throughout the course of virus
      infection.

PMID- 28768416
TI  - Manganese and Cobalt in the Nonheme-Metal-Binding Site of a Biosynthetic Model of
      Heme-Copper Oxidase Superfamily Confer Oxidase Activity through Redox-Inactive
      Mechanism.
AB  - The presence of a nonheme metal, such as copper and iron, in the heme-copper
      oxidase (HCO) superfamily is critical to the enzymatic activity of reducing O2 to
      H2O, but the exact mechanism the nonheme metal ion uses to confer and fine-tune
      the activity remains to be understood. We herein report that manganese and cobalt
      can bind to the same nonheme site and confer HCO activity in a heme-nonheme
      biosynthetic model in myoglobin. While the initial rates of O2 reduction by the
      Mn, Fe, and Co derivatives are similar, the percentages of reactive oxygen
      species (ROS) formation are 7%, 4%, and 1% and the total turnovers are 5.1 +/-
      1.1, 13.4 +/- 0.7, and 82.5 +/- 2.5, respectively. These results correlate with
      the trends of nonheme-metal-binding dissociation constants (35, 22, and 9 MUM)
      closely, suggesting that tighter metal binding can prevent ROS release from the
      active site, lessen damage to the protein, and produce higher total turnover
      numbers. Detailed spectroscopic, electrochemical, and computational studies found
      no evidence of redox cycling of manganese or cobalt in the enzymatic reactions
      and suggest that structural and electronic effects related to the presence of
      different nonheme metals lead to the observed differences in reactivity. This
      study of the roles of nonheme metal ions beyond the Cu and Fe found in native
      enzymes has provided deeper insights into nature's choice of metal ion and
      reaction mechanism and allows for finer control of the enzymatic activity, which
      is a basis for the design of efficient catalysts for the oxygen reduction
      reaction in fuel cells.

PMID- 28768418
TI  - Spotlights: Volume 8, Issue 15.

PMID- 28768417
TI  - In the Limelight.

PMID- 28768419
TI  - Lipid droplets exhaustion with caspases activation in HeLa cells cultured in
      plasma-activated medium observed by multiplex coherent anti-Stokes Raman
      scattering microscopy.
AB  - The multiplex coherent anti-Stokes Raman scattering microscopy allowed label-free
      visualization of cytoplasmic lipid droplets (LDs). The LDs, which act to conserve
      energy storage, are usually accumulated during the normal apoptosis of HeLa cells
      with activation of caspase-3/7 leading to downregulation of the fatty acid
      catabolism pathways. During cultivating in nonthermal plasma-activated medium
      (PAM), while the activation of caspase-3/7 was induced, the authors found that a
      dynamic exhaustion of the intracellular LDs, underlying the metabolic mechanism
      of the PAM-induced apoptotic cell death of HeLa cells.

PMID- 28768420
TI  - Sputter coated ZnO thin films on glass and polycarbonate: Evaluation of stability
      and interaction with Flavin adenine dinucleotide-dependent oxidases.
AB  - Aqueous stability of sputter coated ZnO thin films were studied on two base
      materials, viz., polycarbonate (PC) and glass. The films showed higher stability
      on PC compared to glass, when exposed to aqueous buffered solution at pH-7.4, as
      studied by x-ray diffraction, surface reflectometry, and inductively coupled
      plasma-optical emission spectroscopy. Glucose oxidase (GOx) and cholesterol
      oxidase (Chl.Ox.) were used as model enzymes to study their electrochemical
      interaction with ZnO/PC. GOx showed a higher immobilization on ZnO/PC with an
      activity of 9.2 +/- 1.7 mU cm-2 compared to Chl.Ox. with an activity of 2.79 +/-
      0.5 mU cm-2. This is attributed to the larger crystallite size and higher Zn per
      unit area on PC as compared to glass which enabled a higher activity of GOx on
      ZnO/PC compared to ZnO/glass. Immobilization was mainly dependent on the surface
      residue and the charge of the enzyme as indicated by zeta potential which showed 
      23 mV for GOx compared to -6 mV for Chl.Ox. under physiological conditions.
      Further under unstirred condition, the reaction was limited by diffusion of the
      substrate for the enzyme. Chl.Ox. showed a lower activity as compared to GOx on
      the surface due to low diffusional coefficient of the bulky cholesterol molecule
      as compared to glucose. It was confirmed by low charge transfer resistance in
      electrochemical impedance spectroscopy for GOx (1.51 +/- 0.072 * 105 Omega) as
      compared to Chl.Ox. (1.98 +/- 0.09 * 105 Omega). But under stirring condition,
      the diffusion limitation was overcome, and the sensitivity for Chl.Ox./ZnO was
      11.2 MUA cm-2 mM-1 as compared to GOx/ZnO/PC with 3.5 MUA cm-2 mM-1. Thus,
      sputter coated ZnO thin films appeared to be good quality transducers for
      immobilization of oxidases with sensitivity dependent on the substrate diffusion
      and its potential application in biosensors.

PMID- 28768421
TI  - Constituents from solid-cultured Antrodia camphorata.
AB  - Antrodia camphorata is a rare and precious traditional food and medicine for
      improving health-related conditions in Taiwan. The phytochemical research of the
      mushroom led to the isolation of a new naphthalenecarboxaldehyde, named as 1
      Naphthalenecarboxaldehyde,3,4,4a,5,6,7,8,8a-octahydro-2-(hydroxymethyl)-5,5,8a
      trimethyl (1). Meanwhile, seven other known compounds of nerolidol (2), cadinol
      (3), herbarulide (4), 3beta-Hydroxy-5a,8a-epidioxyergosta-6,22-diene (5), ergosta
      7,22-diene-3,6-dione (6) 2,3-dimethoxy-5-methyl-p-benzoquinone (7) and beta
      sitosterol (8) were also obtained from A. camphorata for the first time except
      compound (8). The new compound was elucidated by 2D NMR techniques (COSY, HMBC,
      HSQC, NOESY) and HRMS while those known compounds deduced by comparing 1H NMR and
      13C NMR data with other literatures. Then, the hepG2 cell toxicity screening was
      conducted and the results demonstrated that only compound 7 and 8 exhibited
      significant toxicity to hepG2 cell at the concentration of 50 MUg/mL.

PMID- 28768422
TI  - Influence of anisotropic bone properties on the biomechanical behavior of the
      acetabular cup implant: a multiscale finite element study.
AB  - Although the biomechanical behavior of the acetabular cup (AC) implant is
      determinant for the surgical success, it remains difficult to be assessed due to
      the multiscale and anisotropic nature of bone tissue. The aim of the present
      study was to investigate the influence of the anisotropic properties of peri
      implant trabecular bone tissue on the biomechanical behavior of the AC implant at
      the macroscopic scale. Thirteen bovine trabecular bone samples were imaged using
      micro-computed tomography (MUCT) with a resolution of 18 MUm. The anisotropic
      biomechanical properties of each sample were determined at the scale of the
      centimeter based on a dedicated method using asymptotic homogenization. The
      material properties obtained with this multiscale approach were used as input
      data in a 3D finite element model to simulate the macroscopic mechanical behavior
      of the AC implant under different loading conditions. The largest stress and
      strain magnitudes were found around the equatorial rim and in the polar area of
      the AC implant. All macroscopic stiffness quantities were significantly
      correlated (R2 > 0.85, p < 6.5 e-6) with BV/TV (bone volume/total volume).
      Moreover, the maximum value of the von Mises stress field was significantly
      correlated with BV/TV (R2 > 0.61, p < 1.6 e-3) and was always found at the bone
      implant interface. However, the mean value of the microscopic stress (at the
      scale of the trabeculae) decrease as a function of BV/TV for vertical and
      torsional loading and do not depend on BV/TV for horizontal loading. These
      results highlight the importance of the anisotropic properties of bone tissue.

PMID- 28768423
TI  - Biomechanical comparison of conventional and optimised locking plates for the
      fixation of intraarticular calcaneal fractures: a finite element analysis.
AB  - Intraarticular calcaneal fractures can result in poor prognosis. Although
      operative fixation can improve the functional outcomes in most cases, surgical
      complications such as loss of reduction and wound healing problems may increase
      the risk of reoperation. Hence, this study aimed to design calcaneal locking
      plate with a lower profile and better biomechanical performance   and to compare
      the redesigned plate with the traditional calcaneal plate via the finite element
      method. A Sanders' type II-C intraarticular calcaneal fracture was simulated. Two
      fixation models utilising the branch-like calcaneal locking plate and the full
      plate were constructed. Topology optimisation was conducted to generate a new
      calcaneal plate design. A biomechanical comparison among the three groups of
      plates was performed using the finite element method. For the fracture simulated
      in this study, the optimised plate was superior to the traditional plate in terms
      of fixation stability and safety but was reduced in volume by approximately
      12.34%. In addition, more rational stress distributions were observed in the
      redesigned plate, underscoring the superiority of this new design in terms of
      fatigue strength. These results demonstrate that the topology optimisation can be
      used to design a new implant with a minimised profile and no loss of fixation
      stability.

PMID- 28768424
TI  - Surgical salvage of recurrence after resection of colorectal liver metastases:
      incidence and outcomes.
AB  - Surgical resection remains the primary curative treatment option for patients
      with colorectal liver metastases. While the majority of patients will develop
      tumor relapse within or outside of the liver after hepatic metastasectomy, a
      subset of these patients may be amenable to salvage surgical resection. However,
      outcomes for this approach are not well defined. In this article, we summarize
      the current evidence for the incidence, feasibility and outcomes of salvage
      resection for recurrence after initial resection of colorectal liver metastases.

PMID- 28768425
TI  - Antibacterial Activity of Hydroxytyrosol Acetate from Olive Leaves (Olea Europaea
      L.).
AB  - Vibrio spp. are pathogens of many bacterial diseases which have caused great
      economic losses in marine aquaculture. The strategy of alternative medical
      treatment that is utilised by herbalists has expanded in the past decade. The aim
      of our study is to discover the antibacterial molecules against Vibrio spp.
      Bacterial growth inhibition, membrane permeabilisation assessment and DNA
      interaction assays, as well as agarose gel electrophoresis, were employed to
      elucidate the antibacterial activity of hydroxytyrosol acetate. Results showed
      that hydroxytyrosol acetate had antibacterial activity against Vibrio spp. and it
      played the role via increasing bacterial membrane permeabilisation. The DNA
      interaction assay and agarose gel electrophoresis revealed that hydroxytyrosol
      acetate interacted with DNA. Hydroxytyrosol acetate enhanced the fluorescent
      intensity of DNA binding molecules and mediated supercoiled DNA relaxation. The
      present study provides more evidence that hydroxytyrosol acetate is a novel
      antibacterial candidate against Vibrio spp.

PMID- 28768426
TI  - Necrotising fasciitis in a patient treated with FOLFIRI-aflibercept for
      colorectal cancer: a case report.
AB  - Anti-angiogenics have become an important part of the treatment of several types
      of tumours such as ovarian, breast, lung and colorectal cancer. Necrotising
      fasciitis has been reported with bevacizumab but no cases have been reported with
      aflibercept, ramucirumab or regorafenib in patients with colorectal cancer.
      Necrotising fasciitis is a rare complication affecting one in 5000 bevacizumab
      users. We report the case of a 64-year-old man with stage IV rectosigmoid cancer
      under treatment with folinic acid, fluorouracil and irinotecan (FOLFIRI) and
      aflibercept, who developed a Fournier's gangrene.

PMID- 28768428
TI  - Evaluation of antiplasmodial properties of a cyanobacterium, Spirulina platensis
      and its mechanism of action.
AB  - The rapid emergence of antimalarial drug resistance necessitates a continual
      effort on novel drug discovery. A cyanobacterium, Spirulina platensis, is a
      potential antimalarial agent that has been widely consumed as food supplement in
      the form of crude extract. It is known to possess antiviral, antibacterial and
      antifungi activities. This study examined the antimalarial activities of several
      Spirulina formulas against Plasmodium falciparum 3D7, in vitro. The tested
      Spirulina formulas included commercially available capsule, crude extract and
      alkaloid fraction. Results showed that all tested formula possessed antimalarial
      activities with the Spirulina capsule exhibited the highest activities (IC50 =
      2.16 MUg/mL). Light and electron microscopies revealed interference of the
      Spirulina with the parasite hemozoin formation. In conclusion, all tested
      Spirulina formulas and fraction exhibited moderate to high antimalarial
      activities.

PMID- 28768429
TI  - Two new monoterpenoid indole alkaloids from Alstonia rostrata.
AB  - Two new indole alkaloids, winphyllines A (1) and B (4), along with four known
      alkaloids, Nb-demethylechitamine (2), 17-O-acetylnorechitamine (3), 12
      methoxyechitamidine (5), and N(4)-demethylastogustine (6), were isolated from the
      methanol extract of the twigs of Alstonia rostrata. The structures of 1 and 4
      were elucidated by means of HRMS and NMR spectroscopic methods. The in vitro
      cytotoxic activity of the isolated alkaloids against several human cancer cell
      lines was evaluated.

PMID- 28768427
TI  - Enhanced recovery programmes for lower limb arthroplasty in the UK.
AB  - Introduction Enhanced recovery programmes (ERPs) reduce patient morbidity and
      mortality, and provide significant cost savings by reducing length of stay.
      Currently, no uniform ERP guidelines exist for lower limb arthroplasty in the UK.
      The aim of this study was to identify variations in ERPs and determine adherence
      to local policy. Methods Hospitals offering elective total knee arthroplasty
      (TKA) and total hip arthroplasty (THA) (23 and 22 centres respectively)
      contributed details of their ERPs, and performed an audit (15 patients per
      centre) to assess compliance. Results Contrasting content and detail of ERPs was
      noted across centres. Adherence to ERPs varied significantly (40-100% for TKA, 17
      94% for THA). Analysis identified perioperative use of dexamethasone, tranexamic
      acid and early mobilisation for TKA, and procedures performed in teaching
      hospitals for THA as being associated with a reduced length of stay. Conclusions
      This study highlights variation in practice and poor compliance with local ERPs.
      Given the proven benefits of ERPs, evidence-based guidelines in the context of
      local skillsets should be established to optimise the patient care pathway.

PMID- 28768430
TI  - Multi- and univariate analyses of the weekend effect for elective lower-limb
      joint replacements.
AB  - Introduction The weekend effect is a perceived difference in outcome between
      medical care provided at the weekend when compared to that of a weekday. Clearly
      multifactorial, this effect remains incompletely understood and variable in
      different clinical contexts. In this study we analyse factors relevant to the
      weekend effect in elective lower-limb joint replacement at a large NHS
      multispecialty academic healthcare centre. Materials and Methods We reviewed the
      electronic medical records of 352 consecutive patients who received an elective
      primary hip or knee arthroplasty. Patient, clinical and time-related variables
      were extracted from the records. The data were anonymised, then processed using a
      combination of uni- and multivariate statistics. Results There is a significant
      association between the selected weekend effect outcome measure (postoperative
      length of stay) and patient age, American Society of Anesthesiologists
      classification, time to first postoperative physiotherapy and time to
      postoperative radiography but not day of the week of operation. Discussion We
      were not able to demonstrate a weekend effect in elective lower-limb joint
      replacement at our institution nor identify a factor that would require
      additional weekend clinical medical staffing. Rather, resource priorities would
      seem to include measures to optimise at-risk patients preoperatively and measures
      to reduce time to physiotherapy and radiography postoperatively. Conclusions Our
      findings imply that postoperative length of stay could be minimised by strategies
      relating to patient selection and access to postoperative services. We have also
      identified a powerful statistical methodology that could be applied to other
      service evaluations in different clinical contexts.

PMID- 28768431
TI  - Adefovir dipivoxil loaded proliposomal powders with improved hepatoprotective
      activity: formulation, optimization, pharmacokinetic, and biodistribution
      studies.
AB  - The present study aimed to prepare proliposomal formulae for improving the oral
      bioavailability of adefovir dipivoxil (AD), a nucleoside reverse transcriptase
      inhibitor effective against hepatitis B virus (HBV). The prepared proliposomal
      formulae were characterized for entrapment efficiency (E.E.%), vesicle size and
      in vitro drug release after reconstitution to conventional liposomes. The
      optimized formula (F9) with a maximum desirability value of 0.858 was selected
      having E.E.% of 71 +/- 3.3% with an average vesicle size of 164.6 +/- 5 nm.
      Moreover, the crystallization of AD within the optimized formula investigated via
      powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC)
      confirmed the presence of the drug in an amorphous state within the lipid
      vesicles with enhanced stability over a storage period of 12 months.
      Thioacetamide-induced liver damage in rats evidenced by elevated liver enzymes
      was significantly improved after treatment with the optimum formula.
      Pharmacokinetic and biodistribution studies of formula F9 showed a higher
      accumulation of AD in the liver with enhanced bioavailability compared to AD
      suspension which highlights its potential advantage for an effective treatment of
      chronic HBV. Hence, proliposomal drug delivery is considered as a better choice
      for the oral delivery of AD.

PMID- 28768433
TI  - Editorial.

PMID- 28768432
TI  - Effects of Surgical Factors on Cartilage Can Be Detected Using Quantitative
      Magnetic Resonance Imaging After Anterior Cruciate Ligament Reconstruction.
AB  - BACKGROUND: Quantitative magnetic resonance (qMR) can be used to measure
      macromolecules in tissues and is a potential method of observing early cartilage
      changes in the development of posttraumatic osteoarthritis. Hypothesis/Purpose:
      We hypothesized that specific patient and surgical factors affecting cartilage
      matrix composition after anterior cruciate ligament (ACL) reconstruction (ACLR)
      can be detected using T1rho and T2 relaxation times. Our purpose was to
      demonstrate this ability in a multicenter feasibility study. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: A total of 54 patients who underwent ACLR
      underwent bilateral MRI at baseline before surgery and 6 months postoperatively.
      Operative findings were recorded. T1rho and T2 relaxation times were calculated
      for 6 cartilage regions: the medial femur, lateral femur, medial tibia, lateral
      tibia, patella, and trochlea. A paired t test compared relaxation times at
      baseline and 6 months, univariate regression identified regions that influenced
      patient-reported outcome measures, and analysis of covariance was used to
      determine the surgical factors that resulted in elevated relaxation times at 6
      months. RESULTS: The injured knee had significantly prolonged T1rho and T2
      relaxation times in the tibiofemoral compartment at baseline and 6 months but had
      shorter values in the patellofemoral compartment compared with the uninjured
      knee. Prolonged T1rho and T2 times at 6 months were noted for both the injured
      and uninjured knees. At 6 months, prolongation of T1rho and T2 times in the
      tibial region was associated with lower patient-reported outcome measures. ACLR
      performed within 30 days of injury had significantly shorter T1rho times in the
      tibial regions, and lateral meniscal tears treated with repair had significantly
      shorter T1rho times than those treated with excision. CONCLUSION: Prolonged
      relaxation times in multiple regions demonstrate how the injury affects the
      entire joint after an ACL tear. Changes observed in the uninjured knee may be
      caused by increased loading during rehabilitation, especially in the
      patellofemoral articular cartilage and distal femur. Relaxation times in the
      tibial regions may be predictive of patient symptoms at 6 months. These same
      regions are affected by surgical timing as early as 30 days after injury, but
      this may partially be reflective of the severity of the preoperative injury and
      the choice of treatment of meniscal tears.

PMID- 28768434
TI  - Metabolic reprogramming during hepatitis B disease progression offers novel
      diagnostic and therapeutic opportunities.
AB  - Metabolic remodeling occurs in immune cells during an infection. Host cells must
      upregulate energy production for growth, proliferation, and effector functions to
      limit the damage imposed by pathogens. One example, the hepatitis B virus,
      induces hepatic injury in human hepatocytes through dysregulation of aerobic
      glycolysis and lipid metabolism. Increased glycolytic metabolism mediated by
      elevated expression of Glut1, glucose influx, and lactate secretion is associated
      with this Warburg phenotype, a classic metabolic signature also observed in
      cancer cells. This article brings into focus the tight interaction between HBV
      infection and metabolic dysfunction and how these processes facilitate the
      progression of end-stage liver diseases, such as hepatocellular carcinoma. We
      also provide evidence and models by which other viruses such as HIV and Zika
      disrupt their host metabolic machinery. The emergence of the immunometabolism
      field provides novel opportunities to take advantage of intermediary metabolites
      and key metabolic pathways for diagnostic and therapeutic purposes.

PMID- 28768435
TI  - Cycluridine: A novel antiviral effective against flaviviruses.
AB  - This review describes the contemporary state of research for antivirals effective
      against flaviviruses, especially focusing on inhibitors of the pestivirus
      causative agent of bovine viral diarrhoea virus. We highlight cycluridine, an
      originally synthesized Mannich's base [a tetrahydro-2(1H)-pyrimidinones
      derivative], as a highly effective antiviral possessing a strong inhibitory
      effect on bovine viral diarrhoea virus replication. Cycluridine was active
      against replication of a wide variety of bovine viral diarrhoea virus strains in
      cell cultures. The drug-sensitive period in the bovine viral diarrhoea virus
      replication cycle included the latent period and the exponential phase; a 90-min
      delay in the peak of viral RNA synthesis was observed. Cycluridine administered
      orally manifested a pronounced protective effect in calves with natural mucosal
      disease/viral diarrhoea and calves experimentally infected with bovine viral
      diarrhoea virus. Its magnitude of activity and selectivity places cycluridine in
      the lead among all known substances with anti- bovine viral diarrhoea virus
      activity. Additionally, cycluridine applied subcutaneously showed anti-tick-born
      encephalitis virus activity, manifesting a marked protective effect in mice
      infected with tick-born encephalitis virus. Cycluridine could be a prospective
      antiviral in veterinary and medical practice for the treatment of bovine viral
      diarrhoea virus and other flavivirus infections.

PMID- 28768436
TI  - Microbial carbonylation and hydroxylation of 20(R)-panaxadiol by Aspergillus
      niger.
AB  - 20(R)-panaxadiol (PD) was metabolised by the fungus Aspergillus niger AS 3.3926
      to its C-3 carbonylated metabolite and five other hydroxylated metabolites (1-6).
      Their structures were elucidated as 3-oxo-20(R)-panaxadiol (1), 3-oxo-7beta
      hydroxyl- 20(R)-panaxadiol (2), 3-oxo-7beta,23alpha-dihydroxyl-20(R)-panaxadiol
      (3), 3,12-dioxo- 7beta,23beta-dihydroxyl-20(R)-panaxadiol (4), 3-oxo-1alpha,7beta
      dihydroxyl-20(R)-panaxadiol (5) and 3-oxo-7beta,15beta-dihydroxyl-20(R)
      panaxadiol (6) by spectroscopic analysis. Among them, compounds 2-6 were new
      compounds. Pharmacological studies revealed that compound 6 exhibited significant
      anti-hepatic fibrosis activity.

PMID- 28768437
TI  - Clinical descriptors for the recognition of central sensitization pain in
      patients with knee osteoarthritis.
AB  - BACKGROUND: Despite growing awareness of the contribution of central pain
      mechanisms to knee osteoarthritis pain in a subgroup of patients, routine
      evaluation of central sensitization is yet to be incorporated into clinical
      practice. AIM: The objective of this perspective is to design a set of clinical
      descriptors for the recognition of central sensitization in patients with knee
      osteoarthritis that can be implemented in clinical practice. METHODS: A narrative
      review of original research papers was conducted by nine clinicians and
      researchers from seven different countries to reach agreement on clinically
      relevant descriptors. RESULTS: It is proposed that identification of a dominance
      of central sensitization pain is based on descriptors derived from the subjective
      assessment and the physical examination. In the former, clinicians are
      recommended to inquire about intensity and duration of pain and its association
      with structural joint changes, pain distribution, behavior of knee pain, presence
      of neuropathic-like or centrally mediated symptoms and responsiveness to previous
      treatment. The latter includes assessment of response to clinical test,
      mechanical hyperalgesia and allodynia, thermal hyperalgesia, hypoesthesia and
      reduced vibration sense. CONCLUSIONS: This article describes a set of clinically
      relevant descriptors that might indicate the presence of central sensitization in
      patients with knee osteoarthritis in clinical practice. Although based on
      research data, the descriptors proposed in this review require experimental
      testing in future studies. Implications for Rehabilitation Laboratory evaluation
      of central sensitization for people with knee osteoarthritis is yet to be
      incorporated into clinical practice. A set of clinical indicators for the
      recognition of central sensitization in patients with knee osteoarthritis is
      proposed. Although based on research data, the clinical indicators proposed
      require further experimental testing of psychometric properties.

PMID- 28768438
TI  - Caregivers' experiences with the selection and use of assistive technology.
AB  - Qualitative data from a mixed-methods clinical trial are used to examine
      caregivers' experiences with the selection and use of assistive technology to
      facilitate care recipients' independence. Through a thematic analysis of
      interviews from 27 caregivers, three broad themes were identified. "A partial
      peace of mind" described the generally positive psychological impacts from
      assistive technology, mainly reduced stress and a shift in caregiving labour from
      physical tasks to a monitoring role. "Working together" explored the caregivers'
      experiences of receiving assistive technology and the sense of collaboration felt
      by caregivers during the intervention process. Finally, "Overcoming barriers"
      addressed two impediments to accessing assistive technology: lack of funding and
      appointment wait times for service providers. The findings suggest that assistive
      technology provision by prescribers plays a beneficial role in the lives of
      caregivers, but access to such benefits can be hampered by contextual
      constraints. Implications for rehabilitation The study findings have a number of
      implications for rehabilitation practice: Family caregivers can be instrumental
      in determining what assistive technology is needed and then procured. Their
      involvement in the selection process is desirable because assistive technology
      may have both positive and negative impacts on them, and they themselves may use
      the devices chosen. Involving family caregivers as more active partners in the
      process of assistive technology provision may represent a greater time investment
      in the short term, but may contribute to better long-term outcomes for care
      recipients and caregivers as well. Limited access to funding and long appointment
      wait times are potential barriers to obtaining necessary assistive technologies.

PMID- 28768439
TI  - Assessing advanced walking ability in people with stroke using the Groningen
      Meander Walking Test.
AB  - OBJECTIVES: (1) To investigate the intrarater, interrater and test-retest
      reliabilities of the Groningen Meander Walking Test in people with stroke; (2) to
      compare the performance of the Groningen Meander Walking Test between people with
      stroke and healthy older adults; (3) to quantify any correlations between the
      Groningen Meander Walking Test and other stroke-specific impairment measurements;
      and (4) to determine the cut off time that best discriminates between 30 people
      with stroke and 30 age-matched healthy elderly. METHOD: Using a cross-sectional
      design, the Groningen Meander Walking Test was administered along with the Fugl
      Meyer Motor Assessment for the lower extremities, measurement of lower limb
      muscle strength, Berg's Balance Scale, comfortable walking speed, Timed up and Go
      test and Community Integration Measure-Cantonese version. RESULTS: The Groningen
      Meander Walking Test completion times showed excellent intrarater, interrater and
      test-retest reliabilities (ICC = 0.984-1.00). Our study also showed that stroke
      subjects took three times longer (28.8 s) than the healthy subjects (9.0 s) in
      completion times. Both Groningen Meander Walking Test completion times and
      overstep scores significantly correlated with comfortable walking speed and Timed
      up and Go test. The cut off time for people with stroke was 11.98 seconds
      (sensitivity = 0.967; specificity = 1.0) to discriminate against healthy elderly.
      CONCLUSION: The Groningen Meander Walking Test is a highly reliable and valid
      tool for quantifying the advanced walking abilities of people with stroke.
      Implications for Rehabilitation The Groningen Meander Walking Test completion
      times demonstrated excellent intrarater, interrater and test-retest
      reliabilities. The Groningen Meander Walking Test completion times correlates
      well with Berg Balance Scale scores, comfortable walking and Timed Up and Go test
      times. The Groningen Meander Walking Test overstep scores correlates
      significantly to its completion times, Fugl-Myer Assessment-Lower Extremity
      scores, comfortable walking speed and Timed Up and Go test times. A cut off time
      of 11.98s best for Groningen Meander Walking Test completion times discriminates
      people with stroke from healthy elderly with sensitivity of 97% and specificity
      of 100%. The Groningen Meander Walking Test is highly reliable and easy to
      administer in assessing advanced walking abilities in people with stroke.

PMID- 28768440
TI  - Contribution of intraoperative colonoscopy in a colorectal surgery unit.
AB  - OBJECTIVES: Intraoperative colonoscopy (IC) is routinely used in colorectal
      surgery procedures, both oncologic and benign ones. Despite its extensive use
      there is a lack of literature addressing this important issue. The aims of this
      paper are to determine the contributions of this tool, especially considering
      changes in attitude from preoperative designed intervention. MATERIALS AND
      METHODS: This study is a retrospective analysis of a prospective maintained
      database. Patients who underwent colorectal resection and IC during a four-year
      period (2009-2012). The indications for performing IC in our unit are: Incomplete
      preoperative colonoscopy, confirm the exact location of the tumor and polypectomy
      of any lesion distant from the planned resection segment. RESULTS: The success
      rate in performing IC is 100%, including 42% of them made trans-anastomotic. No
      postoperative complications that were attributable to the endoscopy were
      detected. Routine practice led to a change in attitude in 5% of the patients
      analyzed; 2% of the global sample corresponded to synchronous tumors finding. Of
      those patients in whom polypectomies where achieved during the procedure a 14.3%
      of potentially malignant lesions were resected. CONCLUSIONS: Intraoperative
      colonoscopy is a useful and safe tool that in view of these results should be
      taken into account at any colorectal surgery unit. Trans-anastomotic techniques
      do not raise morbidity.

PMID- 28768441
TI  - Retrospective analysis of goal drug level attainment of posaconazole for invasive
      fungal infection prophylaxis in patients with acute myeloid leukemia pre- and
      post-switch to tablet formulation.
AB  - BACKGROUND: Posaconazole is approved for invasive fungal infection prophylaxis in
      patients with hematologic malignancies. Posaconazole suspension is plagued by
      poor oral absorption and dietary requirements that are difficult for patients to
      meet. The delayed-release tablet formulation of posaconazole may be taken without
      regards to meals and has significantly better oral absorption than posaconazole
      suspension. OBJECTIVES: We sought to determine if a switch to posaconazole
      tablets improved steady-state drug level attainment for invasive fungal infection
      prophylaxis in patients with acute myeloid leukemia. METHODS: All adult
      inpatients with acute myeloid leukemia undergoing chemotherapy, who received
      posaconazole for invasive fungal infection prophylaxis between 2012 and 2015,
      were included. The primary outcome was proportion of patients with first
      posaconazole level greater than 700 ng/mL. Secondary outcomes included proportion
      of patients with first posaconazole level greater than 1000 ng/mL, invasive
      fungal infection within 100 days, and adverse drug events. RESULTS: Forty
      patients received posaconazole tablets and 34 patients received suspension.
      Posaconazole levels were significantly higher at first measurement in patients
      receiving tablet than suspension (1296 ng/mL vs. 788 ng/mL, p < 0.01). Thirty
      seven patients receiving tablets had a serum drug level greater than 700 ng/mL on
      first measurement versus 18 receiving suspension (p < 0.01). Patients receiving
      tablets were also more likely to have a serum drug level over 1000 ng/mL on first
      measurement (26 vs. 11, p < 0.01). Rates of invasive fungal infection and adverse
      events were not statistically different. CONCLUSIONS: Patients receiving
      posaconazole tablets attained significantly higher serum drug levels than those
      receiving suspension.

PMID- 28768442
TI  - Differences in medical services in Nordic general practice: a comparative survey
      from the QUALICOPC study.
AB  - OBJECTIVE: We aim to describe medical services provided by Nordic general
      practitioners (GPs), and to explore possible differences between the countries.
      DESIGN AND SETTING: We did a comparative analysis of selected data from the
      Nordic part of the study Quality and Costs of Primary Care in Europe. SUBJECTS:
      875 Nordic GPs (198 Norwegian, 80 Icelandic, 97 Swedish, 212 Danish and 288
      Finnish) answered identical questionnaires regarding their practices. MAIN
      OUTCOME MEASURES: The GPs indicated which equipment they used in practice, which
      procedures that were carried out, and to what extent they were involved in
      treatment/follow-up of a selection of diagnoses. RESULTS: The Danish GPs
      performed minor surgical procedures significantly less frequent than GPs in all
      other countries, although they inserted intrauterine devices significantly more
      often than GPs in Iceland, Sweden and Finland. Finnish GPs performed a majority
      of the medical procedures more frequently than GPs in the other countries. The
      GPs in Iceland reported involvement in a more narrow selection of conditions than
      the GPs in the other countries. The Finnish GPs had more advanced technical
      equipment than GPs in all other Nordic countries. CONCLUSION: GPs in all Nordic
      countries are well equipped and offer a wide range of medical services, yet with
      a substantial variation between countries. There was no clear pattern of GPs in
      one country doing consistently more procedures, having consistently more
      equipment and treating a larger diversity of medical conditions than GPs in the
      other countries. However, structural factors seemed to affect the services
      offered.

PMID- 28768443
TI  - Neurobrucellosis.
AB  - PURPOSE: Neurobrucellosis (NB) is a rare complication of brucellosis. NB presents
      with avariety of clinical manifestations, and the symptoms are always atypical.
      Our aim was to analyze the demographic characteristics, clinical manifestations,
      laboratory findings, imaging findings, treatments and outcomes of patients with
      NB. MATERIAL AND METHOD: We retrospectively reviewed the data from 17 patients
      with NB hospitalized at the Chinese People's Liberation Army General Hospital
      between 1 January 2005 and 31 October 2016. RESULTS: The following symptoms were
      recorded: 10/17 (59%) patients had fever, and 9/17 (53%) patients had a disorder
      affecting urination and defecation. Involvement of the cranial nerves was
      documented in 12/17 (71%) patients. The positivity rates of the tests were as
      follows: serum standard tube agglutination (STA), 15/17 (88.2%); cerebrospinal
      fluid STA, 10/17 (59%). The radiologic findings were categorized into four types:
      normal, white matter changes, vascular insult and inflammatory changes. Patients
      were treated with different combinations of rifampicin, doxycycline, ceftriaxone
      sodium and sulphamethoxazole for a total of six months. Two (12%) patients
      deteriorated, and two (12%) patients were lost to follow-up. The remaining
      patients (76%) were cured, but sequelae occurred in six patients. CONCLUSIONS: NB
      should be kept in mind in patients with autonomic dysfunction, especially
      disorders of urination and defecation. Hearing loss due to vestibulocochlear
      nerve injury seems to be typical for NB. The high incidence of sequelae may be
      related to a long disease course and the involvement of the central nervous
      system. Early detection, diagnosis and treatment could decrease mortality and
      sequelae.

PMID- 28768444
TI  - A Swedish version of the Consultation and Relational Empathy (CARE) measure.
AB  - OBJECTIVE: A validated measure to gather patient feedback on physicians' empathy
      is not available in Swedish. The objective for this study was to examine the
      psychometric characteristics of a Swedish version of the Consultation and
      Relational Empathy (CARE) measure (widely used in English). DESIGN, SETTING AND
      PATIENTS: The CARE measure was translated into Swedish and tested on 554
      unselected patients visiting physicians in two primary care clinics in
      northwestern Stockholm, Sweden. MAIN OUTCOME MEASURES: Adequate translation, as
      well as reliability and validity of the Swedish CARE measure. RESULTS: The
      Swedish CARE measure seemed to demonstrate high acceptability and face validity
      when consulting a physician. The mean CARE score 41.5 (SD 8.9) over all 10 item
      was not significantly influenced by seasonality, age or gender. Scores were
      somewhat negatively distributed, but corrected item-total correlations were high
      (0.86-0.91) suggesting homogeneity. Internal reliability was very high
      (Cronbach's alpha 0.975). Factor analysis implied a one-dimensional structure
      with factor loadings between 0.89 and 0.93. CONCLUSIONS: The Swedish CARE measure
      appears to be psychometrically valid and reliable enough in physicians.

PMID- 28768445
TI  - Single-walled carbon nanotube, multi-walled carbon nanotube and Fe2O3
      nanoparticles induced mitochondria mediated apoptosis in melanoma cells.
AB  - PURPOSE: Nanomaterials (NM) exhibit novel anticancer properties. MATERIALS AND
      METHODS: The toxicity of three nanoparticles that are currently being produced in
      high tonnage including single-walled carbon nanotube (SWCNT), multi-walled carbon
      nanotube (MWCNT) and Fe2O3 nanoparticles, were compared with normal and melanoma
      cells. RESULTS: All tested nanoparticles induced selective toxicity and caspase 3
      activation through mitochondria pathway in melanoma cells and mitochondria cause
      the generating of reactive oxygen species (ROS), mitochondrial membrane potential
      decline (MMP collapse), mitochondria swelling, and cytochrome c release. The
      pretreatment of butylated hydroxytoluene (BHT), a cell-permeable antioxidant and
      cyclosporine A (Cs. A), a mitochondrial permeability transition (MPT), pore
      sealing agent decreased cytotoxicity, caspase 3 activation, ROS generation, and
      mitochondrial damages induced by SWCNT, MWCNT, and IONPs. CONCLUSIONS: Our
      promising results provide a potential approach for the future therapeutic use of
      SWCNT, MWCNT, and IONPs in melanoma through mitochondrial targeting.

PMID- 28768446
TI  - Comparison of two doses of intravenous temsirolimus in patients with
      relapsed/refractory mantle cell lymphoma.
AB  - Temsirolimus 175 mg once-weekly for 3 weeks, followed by 75 mg once-weekly
      intravenously dosed (175/75 mg) is approved in the European Union for treatment
      of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored
      whether similar efficacy, but improved safety could be achieved with 75 mg
      without 175 mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with
      relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75 mg (n
      = 47) or 75 mg (n = 42). Treatment continued until objective disease progression.
      Primary endpoint: progression-free survival (PFS). Secondary endpoints included
      overall survival (OS) and adverse events (AEs). Median PFS was 4.3 versus 4.5
      months (hazard ratio [HR] 0.731; 80% confidence interval [CI], 0.520-1.027), and
      median OS 18.7 versus 11.0 months (HR 0.681; 80% CI, 0.472-0.982) with 175/75 mg
      versus 75 mg. There were fewer patients with serious AEs, dose reduction, or
      death with 175/75 mg (57.4%, 48.9%, and 48.9%) versus 75 mg (73.8%, 64.3%, and
      65.1%). Temsirolimus 175/75 mg remains the preferred dosing regimen for
      relapsed/refractory MCL.

PMID- 28768447
TI  - Neural Oscillation Correlates Chemistry Decision-Making.
AB  - This study explored the electroencephalography (EEG) dynamics during a chemistry
      related decision-making task and further examined whether the correctness of the
      decision-making performance could be reflected by EEG activity. A total of 66
      undergraduate students' EEG were collected while they participated in a chemistry
      related decision-making task in which they had to retrieve the relevant chemistry
      concepts in order to make correct decisions for each task item. The results
      showed that it was only in the anterior cingulate cortex (ACC) cluster that
      distinct patterns in EEG dynamics were displayed for the correct and incorrect
      responses. The logistic regression results indicated that ACC theta power from
      300[Formula: see text]ms to 250[Formula: see text]ms before stimulus onset was
      the most informative factor for estimating the likelihood of making correct
      decisions in the chemistry-related decision-making task, while it was the ACC low
      beta power from 150[Formula: see text]ms to 250[Formula: see text]ms after
      stimulus onset. The results suggested that the ACC theta augmentation before the
      stimulus onset serves to actively maintain the relevant information for retrieval
      from long-term memory, while the ACC low beta augmentation after the stimulus
      onset may serve the function of mapping the encoded stimulus onto the relevant
      criteria that the given participant has held within his or her mind to guide the
      decision-making responses.

PMID- 28768448
TI  - Resistance phenotypes and susceptibility of contemporary Serratia isolates in the
      university hospital of Crete, Greece.
AB  - OBJECTIVE: To study changes in the susceptibility of Serratia spp. in Crete,
      Greece (2010-2015). METHODS: Non-duplicate isolates were examined using automated
      systems. Phenotypic confirmatory tests were applied. RESULTS: Three hundred and
      seventy-eight Serratia spp. were analyzed. Serratia marcescens (88.3%) was the
      predominant species. Fluoroquinolones (97.9%), carbapenems (97.4%) and fosfomycin
      (97.4%) were the most active followed by amikacin (95.5%),
      piperacillin/tazobactam (94.7%), and trimethoprim/sulfamethoxazole (94.4%). The
      activity of 3rd and 4th generation cephalosporins was 87-88.6%. The distribution
      of multi-drug resistant (MDR) strains varied, with a trend towards increasing
      frequency. ESBL (7.9%), carbapenemase (2.9%), AmpC (2.1%) and aminoglycoside
      modifying enzyme (10.6%) production were the commonest resistant phenotypes.
      CONCLUSION: The susceptibility of Serratia spp. varied during the study period a
      trend towards decreasing susceptibility, especially for non-carbapenem beta
      lactams and aminoglycosides.

PMID- 28768449
TI  - Recurrent FUO due to intermittent Enterobacter cloacae bacteremias from an
      infected pacemaker lead diagnosed by gallium scan.
AB  - Fever of unknown origin (FUO) refers to fevers of >=101 degrees  F that persist
      for >=3 weeks and remain undiagnosed after a focused inpatient or outpatient
      workup. FUO may be due to infectious, malignant/neoplastic,
      rheumatic/inflammatory, or miscellaneous disorders. Recurrent FUOs are due to the
      same causes of classical FUOs. Recurrent FUOs may have continuous or intermittent
      fevers and are particularly difficult to diagnose. With intermittent fever,
      recurrent FUO diagnostic tests are best obtained during fever episodes. With
      recurrent FUOs, the periodicity of febrile episodes is unpredictable. We present
      a case of a 70-year-old male who presented with recurrent FUO. Multiple extensive
      FUO workups failed to determine the source of his fever. During his last two
      episodes of fever/chills, blood cultures were positive for Enterobacter cloacae.
      Episodic E. cloacae bacteremias suggested a device-related infection, and the
      patient had a penile implant and permanent pacemaker (PPM). Following febrile
      episodes, he was treated with multiple courses of appropriate antibiotics, but
      subsequently fever/chills recurred. Since a device-associated infection was
      suspected, indium and PET scans were done, but were negative. The source of his
      intermittent E. cloacae bacteremias was finally demonstrated by gallium scan
      showing enhanced uptake on a cardiac lead, but not the penile implant or PPM.
      Gallium scanning remains useful in workup of FUOs, particularly when false
      negative indium or PET scans are suspected. The involved pacemaker lead was
      explanted, grew E. cloacae and the patient has since remained fever free.

PMID- 28768450
TI  - Outcome of dichorionic triamniotic triplet: the experience from an emerging fetal
      therapy center.
AB  - OBJECTIVES: To report a cohort of dichorionic triamniotic (DCTA) triplets with
      access to contemporary fetal interventions. DESIGN: Prospective study. SETTING: A
      regional referral center for the diagnosis and management of complicated multiple
      pregnancies. POPULATION: All DCTA triplets receiving consultation and prenatal
      care at our center from 2010 to 2015. METHODS: The following management
      alternatives for DCTA were offered: 1) expectant management; 2) reduction of one
      or two fetus of the monochorionic (MC) component using radiofrequency ablation
      (RFA) after 16 weeks or potassium chloride (KCL) before 16 weeks, respectively;
      3) reduction of the isolated fetus using KCL before 16 weeks. MAIN OUTCOME
      MEASURE: Survival rate of different management alternatives. RESULTS: A total of
      47 DCTA triplets were included in this study. After consultations on possible
      prognosis and management options, 19 patients chose expectant management, 14
      patients opted RFA to reduce one fetus of the MC component, 14 patients required
      KCL to reduce the MC component. Fetal demise per pregnancy occurred more
      frequently in the subgroup managed expectantly (53%) compared to subgroups
      managed with RFA (7%, p = .02) or KCL (0%, p = .02). Overall survival was
      significantly lower in DCTA triplets managed expectantly (58%) compared to
      subgroup managed with RFA (93%, p < .01) or KCL (100%, p = .04). CONCLUSION:
      Fetal reduction seems to improve perinatal survival in DCTA triplets.

PMID- 28768451
TI  - Microwave ablation: an effective treatment for mild-to-moderate secondary
      hyperparathyroidism in patients undergoing haemodialysis.
AB  - BACKGROUND: Microwave ablation (MWA) is an effective treatment for severe
      secondary hyperparathyroidism (SHPT), but it can also be used for mild-to
      moderate secondary hyperparathyroidism (SHPT). In this randomised, controlled
      study, the efficacy of MWA in the treatment of mild-to-moderate
      hyperparathyroidism is investigated. MATERIALS AND METHODS: We assessed outcomes
      12 months after the randomisation of 28 patients with mild-to-moderate SHPT. The
      subjects received either MWA plus calcitriol or calcitriol alone. The primary end
      points were the rate of achieving target levels of intact parathyroid hormone
      (iPTH), changes in iPTH levels and the rate of patients developing severe SHPT.
      RESULTS: Primary end points: the overall rates of achieving target levels of iPTH
      were comparable between the MWA and calcitriol alone groups (24% vs. 22%, p =
      0.85). However, the rate of iPTH <150 pg/mL (lower limit of the target range) in
      the MWA group was higher than that in the calcitriol alone group (23% vs. 8%, p =
      0.02). The mean iPTH level in the MWA group after MWA was lower than that in the
      calcitriol alone group (373.09 +/- 322.31 vs. 552.28 +/- 361.87 pg/mL, p <
      0.001). There was a significant difference in the change in iPTH levels over time
      within the MWA group (p < 0.001) but not in the calcitriol alone group. Only one
      patient developed severe SHPT in the MWA group, while six patients in the
      calcitriol alone group developed severe SHPT (p = 0.04). CONCLUSIONS: Compared
      with calcitriol alone, MWA plus calcitriol decreases iPTH levels and prevents the
      progression of mild-to-moderate SHPT.

PMID- 28768453
TI  - US Supreme Court Decision May Improve Individual Educational Programs for
      Children With Special Needs.

PMID- 28768452
TI  - Aetiology and clinical features of facial cellulitis: a prospective study.
AB  - BACKGROUND: In the early 20th century, the face was the predominant site of
      cellulitis. Despite a relative decrease in the incidence of facial cellulitis, it
      is still common. There are few studies on this condition during the last decades.
      The aim of this study was to describe contemporary aetiological and clinical
      characteristics of patients admitted to hospital with non-suppurative facial
      cellulitis. METHODS: Patients were included prospectively. Clinical details,
      comorbidities and biochemistry results were recorded. Investigations included
      cultures of skin swab and blood and tests for streptococcal antibodies during the
      acute and convalescent stages. RESULTS: Sixty-five patients were included.
      Serology, cultures and response to penicillin monotherapy identified probable or
      confirmed beta-haemolytic streptococci (BHS) aetiology in 75% (49/65) of cases.
      Significant comorbidities were present in 54% (35/65). Fever, chills or rigors
      before or at admission was noted in 91% (59/65). Patients presented most often
      with sharply demarcated erythema and raised borders (54/64). Penicillin or
      penicillinase-resistant penicillin alone or in combination cured 68% (44/65) of
      the patients. Supplementary clindamycin was used in 28% (18/65), most often only
      for 1-3 days. Only four patients needed a second course of antibiotics. Clinical
      failure was more often seen in patients with non-BHS aetiology (p = .037). Few
      complications were noted; 14.5% (9/62) experienced transient diarrhoea, and only
      one had confirmed Clostridium difficile infection. No patients developed cerebral
      venous sinus thrombosis, and there were no fatalities. CONCLUSIONS: Our findings
      indicate that BHS are the leading cause of facial cellulitis. Most patients
      exhibit sharply demarcated lesions and systemic symptoms. Narrow-spectrum beta
      lactam antibiotics and short hospital stay appear sufficient. Few complications
      and low recurrence rates were seen.

PMID- 28768454
TI  - Insight into the structural requirements of thiophene-3-carbonitriles-based MurF
      inhibitors by 3D-QSAR, molecular docking and molecular dynamics study.
AB  - The discovery of clinically relevant inhibitors against MurF enzyme has proven to
      be a challenging task. In order to get further insight into the structural
      features required for the MurF inhibitory activity, we performed pharmacophore
      and atom-based three-dimensional quantitative structure-activity relationship
      studies for novel thiophene-3-carbonitriles based MurF inhibitors. The five
      feature pharmacophore model was generated using 48 inhibitors having IC50 values
      ranging from 0.18 to 663 MUm. The best-fitted model showed a higher coefficient
      of determination (R2 = 0.978), cross-validation coefficient (Q2 = 0.8835) and
      Pearson coefficient (0.9406) at four component partial least-squares factor. The
      model was validated with external data set and enrichment study. The
      effectiveness of the docking protocol was validated by docking the co
      crystallized ligand into the catalytic pocket of MurF enzyme. Further, binding
      free energy calculated by the molecular mechanics generalized Born surface area
      approach showed that van der Waals and non-polar solvation energy terms are the
      main contributors to ligand binding in the active site of MurF enzyme. A 10-ns
      molecular dynamic simulation was performed to confirm the stability of the 3ZM6
      ligand complex. Four new molecules are also designed as potent MurF inhibitors.
      These results provide insights regarding the development of novel MurF inhibitors
      with better binding affinity.

PMID- 28768455
TI  - Occipital Headaches in Children: Are They a Red Flag?
AB  - Occipital headache is considered a risk factor for serious secondary headache
      pathology. The purpose of our study was to assess the etiology of occipital
      headaches among children visiting the emergency department. Subjects were
      children aged 5 to 18 years who were referred to the emergency department due to
      headaches during the years 2013 to 2014. A total of 314 patients with headaches
      were seen at our emergency department. Thirty-nine patients had occipital
      headaches. Viral infections were the most prevalent final diagnosis (97; 31%),
      followed by migraine (37; 11.8%). None of our patients had a brain tumor. There
      was no difference in final diagnosis between the occipital and nonoccipital
      groups. The most common causes of occipital headaches are viral infections and
      primary headaches. Serious intracranial disorders presenting solely as occipital
      headaches and not accompanied by other neurologic signs are uncommon. Thus,
      occipital headaches should be evaluated in the same manner as other headache
      locations.

PMID- 28768456
TI  - The foundations of measurement and assessment in medical education.
AB  - As a medical educator, you may be directly or indirectly involved in the quality
      of assessments. Measurement has a substantial role in developing the quality of
      assessment questions and student learning. The information provided by
      psychometric data can improve pedagogical issues in medical education. Through
      measurement we are able to assess the learning experiences of students. Standard
      setting plays an important role in assessing the performance quality of students
      as doctors in the future. Presentation of performance data for standard setters
      may contribute towards developing a credible and defensible pass mark. Validity
      and reliability of test scores are the most important factors for developing
      quality assessment questions. Analysis of the answers to individual questions
      provides useful feedback for assessment leads to improve the quality of each
      question, and hence make students' marks fair in terms of diversity and
      ethnicity. Item Characteristic Curves (ICC) can send signals to assessment leads
      to improve the quality of individual questions.

PMID- 28768458
TI  - Second-trimester urinary neutrophil gelatinase-associated lipocalin levels in
      gestational diabetes: preliminary results.
AB  - OBJECTIVE: The objective of this study is to investigate the urinary neutrophil
      gelatinase-associated lipocalin (uNGAL) levels in the second trimester of
      pregnant patients at the time of gestational diabetes mellitus (GDM) screening.
      MATERIALS AND METHODS: Urinary samples from 88 pregnant women who underwent
      gestational diabetes screening test were collected in late second trimester (24
      28 weeks) prospectively. After an overnight fasting, 75 g GTT was performed. The
      blood samples were drawn for measurement of glucose, insulin, and HbA1c. The
      urinary and blood parameters were compared for pregnant women with or without
      gestational diabetes. RESULTS: uNGAL levels were significantly elevated in
      pregnant women with gesting compared with the control groups (p < .014). There
      was a positive correlation between uNGAL and HbA1c levels (p = .001).
      CONCLUSIONS: In the second trimester, at the time of GDM screening, high levels
      of uNGAL indicate tubular injury in GDM cases which seems to be a result of
      hyperglycemia. uNGAL may correlate with an inflammatory renal involvement in GDM.

PMID- 28768457
TI  - Greater delay discounting among girls, but not boys, with ADHD correlates with
      cognitive control.
AB  - Cognitive neuroscience models suggest both reward valuation and cognitive control
      contribute to reward-based decision-making. The current study examined the
      relationship between cognitive control and delay discounting (i.e., choosing
      smaller, immediate over larger, delayed rewards) in a large sample of boys and
      girls diagnosed with attention-deficit/hyperactivity disorder (ADHD; N = 95) and
      typically developing control children (TD; N = 59). Specifically, we examined
      performance on multiple measures of cognitive control (i.e., Go/No-Go task, Stop
      Signal task, and Spatial Span task) and delay discounting (i.e., Classic Delay
      Discounting and Real-Time Delay Discounting tasks), as well as the relationship
      between these measures. Results indicated that sex moderated the effects of group
      on task performance. Specifically, girls with ADHD, but not boys with the
      disorder, exhibited atypical delay discounting of real-time rewards. Results from
      correlational analyses indicated that delay discounting and cognitive control
      were not significantly correlated in the overall sample. Multiple regression
      analyses demonstrated that among girls with ADHD poorer spatial working memory
      and inhibitory control predicted greater real-time discounting. Collectively,
      findings provide support for distinct patterns of cognitive control and delay
      discounting among school-aged girls and boys with ADHD. Additionally, findings
      suggest that among girls with ADHD, those who exhibit relatively poor working
      memory and inhibitory control might be a particularly vulnerable subgroup with
      the greatest propensity to exhibit maladaptive decision-making.

PMID- 28768459
TI  - Association between socioeconomic and health factors and edentulism in people
      aged 65 and older - a population-based survey.
AB  - AIMS: To study edentulism and use of dental services in a population-based sample
      of people aged 65 years and older from northern Sweden and western Finland.
      METHODS: In 2010, people aged 65, 70, 75 and 80 years who were living in one of
      32 municipalities in northern Sweden and western Finland were invited to answer a
      questionnaire as part of the Gerontological Regional Database (GERDA) study ( n =
      6099). The questionnaire contained items related to socioeconomic status, general
      health and edentulism. RESULTS: The prevalence of edentulism was 34.9% in
      Finland, compared with 20.6% in Sweden ( p < 0.001), 31.9% in rural areas,
      compared with 20.9% in urban areas ( p < 0.001), and 25% overall. The prevalence
      of edentulism rose from 17.8% in 65-year-olds, 23.8% in 70-year-olds, 33.5% in 75
      year-olds and 37.3% in 80-year-olds ( p < 0.001), and was 23.8% in women,
      compared with 27% in men ( p < 0.001). In multivariate models, edentulism was
      associated with lower educational level (odds ratio (OR) 2.87, 95% confidence
      interval (CI) 2.31-3.58), low income level (OR 1.7, CI 1.09-1.47), residence in a
      rural area (OR 1.43, CI 1.23-1.66), male sex (OR 1.30, CI 1.12-1.52), dependence
      in instrumental activities of daily living (OR 1.48, CI 1.25-1.74), social
      isolation (OR 1.52, CI 1.17-1.98) and poor self-experienced health (OR 1.38, CI
      1.17-1.62). CONCLUSIONS: One-quarter of the total sample was edentulous, with a
      higher prevalence of edentulism in Finland than in Sweden and in rural than in
      urban areas. Edentulism was associated with socioeconomic, psychological and
      health-related factors. These findings could be used to inform preventive
      measures and identify people aged 65 years and older who are in need of oral
      care.

PMID- 28768460
TI  - A stranger in my brain: Neural representation for unfamiliar persons using fMRI
      repetition suppression.
AB  - Prior neuroimaging research demonstrated that the ventromedial prefrontal cortex
      (vmPFC) houses neural representations for traits and familiar persons that
      possess these traits. But do such neural representations also exist for people we
      do not know? We hypothesized that knowledge about unknown persons is encoded in
      "generic" mentalizing representations as opposed to "specific" representations
      for well-known individuals. Neural representations for unfamiliar persons were
      investigated by fMRI repetition suppression, which is a rapid suppression of fMRI
      responses upon repeated presentation of the same stimulus signaling the neural
      representation of this stimulus. Participants had to infer an unfamiliar person's
      traits from brief behavioral descriptions. In each trial, a critical sentence was
      preceded by another sentence in which we manipulated whether or not the person or
      trait was repeated. The results revealed suppression for unfamiliar others in the
      vmPFC extending earlier research, as well as in novel areas including the
      inferior parietal lobule and dorsal posterior cingulate. We also found trait
      suppression in the vmPFC. This indicates that the vmPFC houses neural populations
      of "generic" representations of unknown persons and their traits. We speculate
      that the other brain areas showing suppression might reflect embodied
      representations at a somatomotor level.

PMID- 28768461
TI  - Quantitative analysis of impact of awareness-raising activities on organic solid
      waste separation behaviour in Balikpapan City, Indonesia.
AB  - Many cities in Indonesia are under pressure to reduce solid waste and dispose of
      it properly. In response to this pressure, the Japan International Cooperation
      Agency and the Indonesian Government have implemented a solid waste separation
      and collection project to reduce solid waste in the target area (810 households)
      of Balikpapan City. We used a cluster randomised controlled trial method to
      measure the impact of awareness-raising activities that were introduced by the
      project on residents' organic solid waste separation behaviour. The level of
      properly separated organic solid waste increased by 6.0% in areas that conducted
      awareness-raising activities. Meanwhile, the level decreased by 3.6% in areas
      that did not conduct similar activities. Therefore, in relative comparison,
      awareness-raising increased the level by 9.6%. A comparison among small
      communities in the target area confirmed that awareness-raising activities had a
      significant impact on organic solid waste separation. High frequencies of
      monitoring at waste stations and door-to-door visits by community members had a
      positive impact on organic solid waste separation. A correlation between the
      proximity of environmental volunteers' houses to waste stations and a high level
      of separation was also confirmed. The awareness-raising activities introduced by
      the project led to a significant increase in the separation of organic solid
      waste.

PMID- 28768462
TI  - Approaches to the field recognition of potential thrombectomy candidates.
AB  - Systems of care for acute ischemic stroke are being challenged to implement
      processes that ensure rapid access to endovascular thrombectomy. Optimizing
      existing regionalized stroke thrombolysis programs for endovascular thrombectomy
      will require accurate field recognition of treatment candidates. We begin with a
      review of the development of early clinical tests for ischemic stroke,
      illustrating challenges relevant to future field tests for large vessel
      occlusion. Second, we discuss aspects of diagnosis, eligibility, feasibility, and
      system organization that are potentially relevant to the development and
      implementation of field tests and diversion criteria. These considerations may
      influence the choice and parametrization of field tests in individual
      jurisdictions. Third, we review the literature evaluating eight clinical tests
      for the field identification of probable large vessel occlusion. All candidate
      tests include evaluations for focal weakness, and six evaluate for cortical signs
      such as aphasia or gaze deviation. Most appear roughly comparable to the NIH
      Stroke Scale, but direct comparison between studies is inappropriate because of
      major methodological differences. Finally, we discuss our jurisdiction's approach
      to the field recognition of thrombectomy candidates. We contextualize diagnostic,
      eligibility, and system considerations within distinct metro and rural
      environments and propose a screen-and-consult model for the rural setting.

PMID- 28768463
TI  - Molecular dynamics simulations investigate the mechanism of Psalmotoxin 1
      regulating gating process of an acid-sensing ion channel 1a at pH 5.5.
AB  - Acid-sensing ion channel 1a (ASIC1a) is a cation channel activated by protons and
      causes neuronal death through central nervous system. Psalmotoxin1 (PcTx1) is a
      gating modifier for ASIC1a. The process of PcTx1 regulating the channel gating
      from the extracellular domain to the transmembrane domain is unclear. Here we
      used molecular dynamics (MD) simulations method to investigate how PcTx1
      regulates the gating of the ASIC1a. Our results indicated that PcTx1can mainly
      regulate ASIC1a gating process through hydrogen bonds, which can affect their
      relative positions of several key domains in ASIC1a, further, a long-range
      conformational changes path was determined, which is composed of beta1, beta2,
      beta10, alpha6, alpha7, beta11, and beta12 in ASIC1a.

PMID- 28768464
TI  - Perception of Belgian nurses about evidence-based clinical practice
      implementation: a focus group study.
AB  - BACKGROUND/OBJECTIVES: Despite recommendations to integrate evidence-based
      practice into nursing care, evidence-based nursing (EBN) implementation is
      generally lacking. Strategies for developing an EBN implementation plan require
      an evaluation of nurses' needs and expectations. The aim of this study was to
      evaluate how Belgian nurses perceive EBN. METHODS: Descriptive qualitative data
      were obtained via focus groups. Fifty-six nurses took part in the study and were
      assigned to one of seven focus groups based on their work setting and the local
      language. RESULTS: The main results revealed little familiarity with the EBN
      concept. There were a number of reported barriers to integrating EBN into
      practice: lack of time; lack of skills needed to find, process, and apply
      information; lack of support from management; and lack of recognition of the
      nursing profession. CONCLUSION: Participants identified four strategies for
      facilitating EBN development: specific staff dedicated to supporting EBN
      implementation; an interactive web-based platform to help nurses find, select,
      and interpret relevant scientific sources; an electronic tool to help nurses in
      clinical decision-making based on patients' clinical data; and a change in
      clinical culture to include EBN in decision-making processes.

PMID- 28768465
TI  - Interaction between Hb E and Hb Yala (HBB:c.129delT); a novel frameshift beta
      globin gene mutation, resulting in Hemoglobin E/beta0 thalassemia.
AB  - OBJECTIVES: There are more than 200 known mutations found in patients with beta
      thalassemia, a possibility to identify an unknown or novel mutation becomes less
      possible. Here, we report a novel mutation in a patient from Thailand who
      presented with chronic hemolytic anemia. METHODS: A comprehensive hematology and
      DNA analysis was applied in the index patient and her mother. RESULTS:
      Hematological and hemoglobin analyses were consistent with the clinical diagnosis
      of Hb E/beta0-thalassemia. However, we could find only Hb E heterozygous mutation
      using our common polymerase chain reaction-based mutation detection of the beta
      globin genes. Furthermore, the molecular analysis demonstrated a novel T-deletion
      at codon 42 of the second exon of the beta-globin gene which we named 'Hb Yala'
      according to the origin of this index family. DISCUSSION: This mutation was
      assumed to generate a truncated beta-globin chain terminating at codon 60 with
      possible unstable variant leading to a 'null' or beta0-thalassemia. However, the
      clinical phenotype was surprisingly mild and no other ameliorating genetic
      factors, including co-inheritance of alpha-thalassemia and high propensity of Hb
      F by Xmn I polymorphism, were found. CONCLUSION: This report has provided
      evidence that genotype-phenotype correlation in thalassemia syndromes is highly
      complex and a correct clinical severity classification of thalassemia should be
      mainly based on clinical evaluation.

PMID- 28768466
TI  - Investigation on the interaction of newly designed potential antibacterial Zn(II)
      complexes with CT-DNA and HSA.
AB  - Two Zn(II) complexes of formula [Zn(bpy)(Gly)]NO3 (I) and [Zn(phen)(Gly)]NO3 (II)
      (where bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline and Gly = glycine) were
      synthesized and characterized by elemental analysis, molar conductance
      measurements, UV-vis, FT-IR, and 1H NMR spectra. The interaction ability of these
      complexes with calf thymus DNA was monitored using spectroscopic methods,
      including UV-vis absorption spectroscopy, ethidium bromide displacement, Fourier
      transform infrared, and electrophoretic mobility assay. Further, the human serum
      albumin interactions of complexes I and II were investigated using UV-vis
      absorption spectroscopy, fluorescence quenching, circular dichroism, and Fourier
      transform infrared. The results obtained from these analyses indicated that both
      complexes interact effectively with CT-DNA and HSA. The binding constant (Kb),
      the Stern-Volmer constant (Ksv), and the number of binding sites (n) at different
      temperatures were determined for CT-DNA and HSA. Also, the negative DeltaH
      degrees  and DeltaS degrees  values showed that both hydrogen bonds and van der
      Waals forces played major roles in the association of CT-DNA-Zn(II) and HSA
      Zn(II) complex formation. The displacement experiments suggested that Zn(II)
      complexes primarily bound to Sudlow's site II of HSA. The distance between the
      donor (HSA) and the acceptor (Zn(II) complexes) was estimated on the basis of the
      Forster resonance energy transfer (FRET) and the alteration of HSA secondary
      structure induced by the compounds were confirmed by FT-IR spectroscopy. The
      complexes follow the binding affinity order of I > II with DNA and II > I with
      HSA. Finally, Antibacterial activity of complexes I and II have been screened
      against gram positive and gram negative bacteria.

PMID- 28768467
TI  - Challenges experienced during rehabilitation after traumatic multiple rib
      fractures: a qualitative study.
AB  - BACKGROUND: People with multiple rib fractures rarely receive rehabilitation
      aimed specifically at their chest wall injuries. This research explores patient
      perceptions of rehabilitation and recovery. MATERIALS AND METHODS: A qualitative
      study exploring how a purposive sample of 15 people with traumatic multiple rib
      fractures at a Major Trauma Centre in the United Kingdom make sense of their
      recovery. Data collected during one-to-one interviews 4 to 9 months after injury.
      Transcripts analysed using Interpretative Phenomenological Analysis. RESULTS:
      Struggling with breathing and pain: Difficulties with breathing and pain were
      initially so severe ?it takes your breath away? and people felt scared they may
      not survive. These symptoms gradually improved but feeling "out of puff" often
      persisted. Life on hold: Healing was considered a natural process which people
      couldn't influence, creating frustration whilst waiting for injuries to heal.
      Many believed they would never fully recover and accepted limitations. Lucky to
      be alive: All participants expressed a sense of feeling lucky to be alive. The
      seriousness of injury prompted a change in attitude to make the most of life.
      CONCLUSION: Rib fractures can be painful, but also frightening. A rehabilitation
      intervention promoting pain management, normalises trauma and restores physical
      activity may improve recovery. Implications for Rehabilitation Patients
      identified challenges with rehabilitation throughout the entire recovery journey,
      and their rehabilitation needs evolved with time. People find it difficult to
      regain pre-injury fitness even after their fractures heal and pain subsides. A
      belief there is nothing that can be done to help rib fractures contributed to
      people lowering their expectations of achieving a full recovery and developing a
      sense of "making do". Rehabilitation and patient education after traumatic
      multiple rib fractures should focus on improving pain management, respiratory
      fitness and emotional well-being.

PMID- 28768468
TI  - Predictive value of exercise-induced atrial natriuretic peptide secretion for the
      presence of left atrial low-voltage areas in patients with persistent atrial
      fibrillation.
AB  - Objectives Left atrial (LA) low-voltage areas (LVAs) are a strong predictor of
      atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI).
      However, a non-invasive method for evaluating LA-LAVs has not been established
      yet. The objective of our study was to assess the predictive value of the plasma
      atrial natriuretic peptide (ANP) level for the presence of LA-LVAs in patients
      with persistent AF (PeAF). Methods Seventy-two PeAF patients underwent an
      exercise stress test preprocedurally. LA voltage maps were created after PVI.
      Demographic, clinical and echocardiographic data were recorded. Plasma levels of
      ANP at baseline (ANP0) and increase induced by exercise (DeltaANP) were also
      measured. Results Compared with patients without LA-LVAs, patients with LA-LVAs
      had a longer history of AF, higher CHADS2 score and higher ANP0 and lower
      DeltaANP. LA-LVAs extent correlated with duration of AF history, CHADS2 score and
      DeltaANP (R = -0.76, P < 0.01). Only DeltaANP independently predicted the
      presence of LA-LVAs (OR =1.63, P = 0.02). Derived from the ROC curve, DeltaANP
      <55 pg/mL predicted the presence of LA-LVAs with high accuracy (AUC =0.78; 95% CI
      =0.57-0.87, P < 0.01). Conclusions Exercise-induced secretion of ANP may be used
      to predict the presence of LA-LVAs in patients with PeAF before catheter
      ablation.

PMID- 28768469
TI  - Novel outreach settings to enhance sexually transmitted infection/HIV awareness,
      diagnosis and treatment in hard-to-reach populations.
AB  - Despite recent rises in the number of cases of sexually transmitted infections
      (STIs) such as syphilis and gonorrhoea in England and increasing rates of HIV
      diagnosis among several men who have sex with men populations, many individuals
      are still not engaging with sexual health services. The John Hunter Clinic for
      Sexual Health, Chelsea and Westminster Hospital, London set up outreach clinics
      at the two world's largest adult lifestyle exhibitions in 2013 and 2015. This was
      the first time that a sexual health screening and promotion service was available
      at these large-scale (over 10,000 attendees at each) adult lifestyle events. A
      total of 381 individuals underwent STI screening across the two events. Nineteen
      (5.0%) patients were diagnosed with an infection. Twelve (3.1%) patients with
      Chlamydia trachomatis, three (0.8%) patients with syphilis, one (0.3%) patient
      with Neisseria gonorrhoeae, one (0.3%) patient with HIV, one (0.3%) patient with
      hepatitis B and one (0.3%) patient with hepatitis C. All 19 patients were
      promptly contacted with their results and had arrangements made for treatment or
      were referred for specialist follow up. Where possible, contact tracing was also
      performed. Implementing such outreach-based projects is challenged by lack of on
      site laboratory support, high staffing demands and potentially high costs.
      However, we achieved a total HIV screening uptake rate of 94.5% amongst our
      outreach clinic attendees (versus 67% nationally in conventional sexual health
      clinic attendees) with an HIV positivity rate of 0.3% (versus 0.2% nationally in
      high HIV prevalence band populations). Additionally, 30.7% had never been tested
      for HIV previously (versus 20.7% nationally). Our work demonstrates that these
      strategies can help to address issues related to lack of STI/HIV screening in
      hard-to-reach populations and promote risk reduction behaviour.

PMID- 28768470
TI  - Misleading 18FDG-PET/CT finding caused by chronic HIV infection in a patient with
      gastric carcinoma: a case report.
AB  - The aim of this study was to describe the influence of HIV infection on the
      staging of gastric cancer by using positron emission tomography/computed
      tomography (PET/CT) imaging. We treated a patient with local advanced gastric
      cancer. PET/CT showed an unusual hypermetabolic activity of lymph nodes, and the
      patient was later found to be HIV-positive. PET/CT scans in cancer staging of
      patients with chronic HIV infection may show advanced stage disease. Spread of
      primary tumor to unusual sites should be a warning sign for the possible
      concurrent diseases.

PMID- 28768471
TI  - Unsuspected human immunodeficiency virus infection presenting as immunoglobulin
      G4-related lymphadenopathy: a case report.
AB  - Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated
      condition characterized by infiltration of the involved organs by IgG4-bearing
      plasma cells. The prevalence of autoimmune diseases, associated with or occurring
      in patients with human immunodeficiency virus (HIV) infection, has been
      increasing. We describe a 58-year-old man with an undiagnosed HIV infection,
      which presented as chronic cervical lymphadenopathy with an elevated serum IgG4
      and a very high IgE. Histologically, lymph nodes showed expanded sinusoids and
      burnt-out germinal centers with increased plasmacytic infiltration and collagen
      fiber deposition. The absolute number of IgG4+ plasma cells and the IgG4+/IgG+
      plasma cell ratio was increased. The lymph nodes were enlarged and clinically the
      patient improved after steroid treatment. Nine months later, he was diagnosed
      with acquired immune deficiency syndrome, following presentation with a cavitary
      left lung lesion. Immunohistochemical studies on the previously resected lymph
      node revealed complete absence of CD4+ T-lymphocytes and increased CD8+ T
      lymphocytes. The pathologic findings met the criteria of both HIV infection and
      IgG4-related lymphadenopathy. Our case demonstrates that further investigations
      for underlying HIV infection in a case of IgG4-RD are critical, especially when
      extremely elevated IgE is concomitantly present.

PMID- 28768472
TI  - Phenotypic integration mediated by hormones: associations among digit ratios,
      body size and testosterone during tadpole development.
AB  - BACKGROUND: Developmental associations often explain phenotypic integration. The
      intersected hormonal regulation of ontogenetic processes fosters predictions of
      steroid-mediated phenotypic integration among sexually dimorphic traits, a
      statement defied by associations between classical dimorphism predictors (e.g.
      body size) and traits that apparently lack sex-specific functions (e.g. ratios
      between the lengths of Digits II and IV - 2D:4D). Developmental bases of female
      biased 2D:4D have been identified, but these remain unclear for taxa presenting
      male-biased 2D:4D (e.g. anura). Here we propose two alternative hypotheses to
      investigate evolution of male-biased 2D:4D associated with sexually dimorphic
      body size using Leptodactylus frogs: I)'hypothesis of sex-specific digit
      responses' - Digit IV would be reactive to testosterone but exhibit responses in
      the opposite direction of those observed in female-biased 2D:4D lineages, so that
      Digit IV turns shorter in males; II) 'hypothesis of identity of the dimorphic
      digit'- Digit II would be the dimorphic digit. RESULTS: We compiled the following
      databases using Leptodactylus frogs: 1) adults of two species from natural
      populations and 2) testosterone-treated L. fuscus at post-metamorphic stage.
      Studied traits seem monomorphic in L. fuscus; L. podicipinus exhibits male-biased
      2D:4D. When present, 2D:4D dimorphism was male-biased and associated with
      dimorphic body size; sex differences resided on Digit II instead of IV,
      corroborating our 'hypothesis of identity of the dimorphic digit'. Developmental
      steroid roles were validated: testosterone-treated L. fuscus frogs were smaller
      and exhibited masculinized 2D:4D, and Digit II was the digit that responded to
      testosterone. CONCLUSION: We propose a model where evolution of sexual dimorphism
      in 2D:4D first originates from the advent, in a given digit, of increased tissue
      sensitivity to steroids. Phenotypic integration with other sexually dimorphic
      traits would then occur through multi-trait hormonal effects during development.
      Such process of phenotypic integration seems fitness-independent in its origin
      and might explain several cases of steroid-mediated integration among sexually
      dimorphic traits.

PMID- 28768473
TI  - A de novo missense mutation of FGFR2 causes facial dysplasia syndrome in Holstein
      cattle.
AB  - BACKGROUND: Surveillance for bovine genetic diseases in Denmark identified a
      hitherto unreported congenital syndrome occurring among progeny of a Holstein
      sire used for artificial breeding. A genetic aetiology due to a dominant
      inheritance with incomplete penetrance or a mosaic germline mutation was
      suspected as all recorded cases were progeny of the same sire. Detailed
      investigations were performed to characterize the syndrome and to reveal its
      cause. RESULTS: Seven malformed calves were submitted examination. All cases
      shared a common morphology with the most striking lesions being severe facial
      dysplasia and complete prolapse of the eyes. Consequently the syndrome was named
      facial dysplasia syndrome (FDS). Furthermore, extensive brain malformations,
      including microencephaly, hydrocephalus, lobation of the cerebral hemispheres and
      compression of the brain were present. Subsequent data analysis of progeny of the
      sire revealed that around 0.5% of his offspring suffered from FDS. High density
      single nucleotide polymorphism (SNP) genotyping data of the seven cases and their
      parents were used to map the defect in the bovine genome. Significant genetic
      linkage was obtained for three regions, including chromosome 26 where whole
      genome sequencing of a case-parent trio revealed two de novo variants perfectly
      associated with the disease: an intronic SNP in the DMBT1 gene and a single non
      synonymous variant in the FGFR2 gene. This FGFR2 missense variant (c.927G>T)
      affects a gene encoding a member of the fibroblast growth factor receptor family,
      where amino acid sequence is highly conserved between members and across species.
      It is predicted to change an evolutionary conserved tryptophan into a cysteine
      residue (p.Trp309Cys). Both variant alleles were proven to result from de novo
      mutation events in the germline of the sire. CONCLUSIONS: FDS is a novel genetic
      disorder of Holstein cattle. Mutations in the human FGFR2 gene are associated
      with various dominant inherited craniofacial dysostosis syndromes. Given the
      phenotypic similarities in FDS affected calves, the genetic mapping and absence
      of further high impact variants in the critical genome regions, it is highly
      likely that the missense mutation in the FGFR2 gene caused the FDS phenotype in a
      dominant mode of inheritance.

PMID- 28768474
TI  - Progesterone in women with arrested premature labor, a report of a randomised
      clinical trial and updated meta-analysis.
AB  - BACKGROUND: Progesterone may be effective in prevention of premature birth in
      some high risk populations. Women with arrested premature labor are at risk of
      recurrent labor and maintenance therapy with standard tocolytics has not been
      successful. METHODS: Randomized double blinded clinical trial of daily treatment
      with 200 mg vaginal progesterone in women with arrested premature labor and an
      updated meta-analysis. RESULTS: The clinical trial was terminated early after 41
      women were enrolled. Vaginal progesterone treatment did not change the median
      gestational age at delivery: 36+2 weeks versus 36+4 weeks, p = .865 nor increase
      the mean latency to delivery: 44.5 days versus 46.6 days, p = .841. In the
      updated meta-analysis, progesterone treatment did reduce delivery <37 weeks
      gestation and increase latency to delivery, but this treatment effect was not
      evident in the high quality trials: (OR 1.23, 95% CI 0.91, 1.67) and (-0.95 days,
      95% CI -5.54, 3.64) respectively. CONCLUSION: Progesterone is not effective for
      preventing preterm birth following arrested preterm labor.

PMID- 28768475
TI  - The cost-utility of point-of-care troponin testing to diagnose acute coronary
      syndrome in primary care.
AB  - BACKGROUND: The added value of using a point-of-care (POC) troponin test in
      primary care to rule out acute coronary syndrome (ACS) is debated because test
      sensitivity is inadequate early after symptom onset. This study investigates the
      potential cost-utility of diagnosing ACS by a general practitioner (GP) when a
      POC troponin test is available versus GP assessment only. METHODS: A patient
      level simulation model was developed, representing a hypothetical cohort of the
      Dutch population (>35 years) consulting the GP with chest complaints. All health
      related consequences as well as cost consequences were included. Both symptom
      duration, selection of patients in whom the POC troponin test is performed, and
      test performance at different time points were incorporated. Health outcomes were
      expressed as Quality-Adjusted Life Years (QALYs). The main outcome parameters
      involve the effect of POC troponin testing on (in)correct hospital referrals,
      QALYs, and costs. RESULTS: The POC troponin strategy decreases the referral rate
      in non-ACS patients from 38.46% to 31.85%. Despite a small increase in non
      referral among ACS patients from 0.22% to 0.27%, the overall health effect is
      negligible. Costs will decrease with ?77.25/patient (95% CI ?-126.81 to ?-33.37).
      CONCLUSIONS: The POC troponin strategy is likely cost-saving, by reducing
      hospital referrals. The small increase in missed ACS patients can be partly
      explained by conservative assumptions used in the analysis. Besides, current
      developments in POC troponin tests will likely further improve their diagnostic
      performance. Therefore, future prospective studies are warranted to investigate
      whether those developments make the POC troponin test to a safe and cost
      effective diagnostic tool for diagnosing ACS in general practices.

PMID- 28768476
TI  - Pan-genome and phylogeny of Bacillus cereus sensu lato.
AB  - BACKGROUND: Bacillus cereus sensu lato (s. l.) is an ecologically diverse
      bacterial group of medical and agricultural significance. In this study, I use
      publicly available genomes and novel bioinformatic workflows to characterize the
      B. cereus s. l. pan-genome and perform the largest phylogenetic and population
      genetic analyses of this group to date in terms of the number of genes and taxa
      included. With these fundamental data in hand, I identify genes associated with
      particular phenotypic traits (i.e., "pan-GWAS" analysis), and quantify the degree
      to which taxa sharing common attributes are phylogenetically clustered. METHODS:
      A rapid k-mer based approach (Mash) was used to create reduced representations of
      selected Bacillus genomes, and a fast distance-based phylogenetic analysis of
      this data (FastME) was performed to determine which species should be included in
      B. cereus s. l. The complete genomes of eight B. cereus s. l. species were
      annotated de novo with Prokka, and these annotations were used by Roary to
      produce the B. cereus s. l. pan-genome. Scoary was used to associate gene
      presence and absence patterns with various phenotypes. The orthologous protein
      sequence clusters produced by Roary were filtered and used to build HaMStR
      databases of gene models that were used in turn to construct phylogenetic data
      matrices. Phylogenetic analyses used RAxML, DendroPy, ClonalFrameML, PAUP*, and
      SplitsTree. Bayesian model-based population genetic analysis assigned taxa to
      clusters using hierBAPS. The genealogical sorting index was used to quantify the
      phylogenetic clustering of taxa sharing common attributes. RESULTS: The B. cereus
      s. l. pan-genome currently consists of ~60,000 genes, ~600 of which are "core"
      (common to at least 99% of taxa sampled). Pan-GWAS analysis revealed genes
      associated with phenotypes such as isolation source, oxygen requirement, and
      ability to cause diseases such as anthrax or food poisoning. Extensive
      phylogenetic analyses using an unprecedented amount of data produced phylogenies
      that were largely concordant with each other and with previous studies.
      Phylogenetic support as measured by bootstrap probabilities increased markedly
      when all suitable pan-genome data was included in phylogenetic analyses, as
      opposed to when only core genes were used. Bayesian population genetic analysis
      recommended subdividing the three major clades of B. cereus s. l. into nine
      clusters. Taxa sharing common traits and species designations exhibited varying
      degrees of phylogenetic clustering. CONCLUSIONS: All phylogenetic analyses
      recapitulated two previously used classification systems, and taxa were
      consistently assigned to the same major clade and group. By including accessory
      genes from the pan-genome in the phylogenetic analyses, I produced an
      exceptionally well-supported phylogeny of 114 complete B. cereus s. l. genomes.
      The best-performing methods were used to produce a phylogeny of all 498 publicly
      available B. cereus s. l. genomes, which was in turn used to compare three
      different classification systems and to test the monophyly status of various B.
      cereus s. l. species. The majority of the methodology used in this study is
      generic and could be leveraged to produce pan-genome estimates and similarly
      robust phylogenetic hypotheses for other bacterial groups.

PMID- 28768477
TI  - Hostplant change and paleoclimatic events explain diversification shifts in
      skipper butterflies (Family: Hesperiidae).
AB  - BACKGROUND: Skippers (Family: Hesperiidae) are a large group of butterflies with
      ca. 4000 species under 567 genera. The lack of a time-calibrated higher-level
      phylogeny of the group has precluded understanding of its evolutionary past. We
      here use a 10-gene dataset to reconstruct the most comprehensive time-calibrated
      phylogeny of the group, and explore factors that affected the diversification of
      these butterflies. RESULTS: Ancestral state reconstructions show that the early
      hesperiid lineages utilized dicots as larval hostplants. The ability to feed on
      monocots evolved once at the K-Pg boundary (ca. 65 million years ago (Mya)), and
      allowed monocot-feeders to diversify much faster on average than dicot-feeders.
      The increased diversification rate of the monocot-feeding clade is specifically
      attributed to rate shifts in two of its descendant lineages. The first rate
      shift, a four-fold increase compared to background rates, happened ca. 50 Mya,
      soon after the Paleocene-Eocene thermal maximum, in a lineage of the subfamily
      Hesperiinae that mostly fed on forest monocots. The second rate shift happened
      ca. 40 Mya in a grass-feeding lineage of Hesperiinae when open-habitat grasslands
      appeared in the Neotropics owing to gradual cooling of the atmospheric
      temperature. CONCLUSIONS: The evolution of monocot feeding strongly influenced
      diversification of skippers. We hypothesize that although monocot feeding was an
      intrinsic trait that allowed exploration of novel niches, the lack of extensive
      availability of monocots comprised an extrinsic limitation for niche exploration.
      The shifts in diversification rate coincided with paleoclimatic events during
      which grasses and forest monocots were diversified.

PMID- 28768478
TI  - Left ventricular systolic function changes in hypertrophic cardiomyopathy
      patients detected by the strain of different myocardium layers and longitudinal
      rotation.
AB  - BACKGROUND: Impairment of left ventricular (LV) longitudinal function has an
      important role in hypertrophic cardiomyopathy (HCM). This research investigated
      an association between the longitudinal strain of different myocardial layers,
      longitudinal rotation and the LV systolic function of HCM patients. METHODS: The
      research was performed on 36 HCM patients and 36 healthy subjects. The peak
      systolic longitudinal strain of the subendocardial, midmyocardial, and
      subepicardial layers was measured using 2-dimensional speckle tracking
      echocardiography (2D-STE). The apical long-axis and 4- and 2- chamber views were
      acquired via 2D Doppler echocardiography. The curve of the longitudinal rotation
      was traced at 17 timepoints in the analysis of 2 cardiac cycles. RESULTS:
      Compared with healthy subjects, in HCM patients regional LV peak systolic
      longitudinal strain was less, not only in hypertrophied LV myocardium, but also
      in non-hypertrophied myocardium. The rotational degrees of the midmyocardial
      septal, apex, and lateral wall of HCM patients were significantly different from
      that of normal subjects, as follows. In HCM patients, clockwise longitudinal
      rotation was found. The interventricular septum thickness at end-diastole
      positively correlated with the peak longitudinal systolic strain of the
      subendocardial, the midmyocardial, and the subepicardial layers. The area under
      ROC curve values for subendocardial, midmyocardial and subepicardial layers in
      HCM patients were 0.923, 0.938, 0.948. CONCLUSION: In HCM patients, the
      longitudinal function was damaged, even with normal LV ejection fraction. The
      peak longitudinal systolic strain of the subendocardial, midmyocardial, and
      subepicardial layers, and the longitudinal rotation detected by 2D-STE, are very
      sensitive predictors of systolic function in patients with HCM.

PMID- 28768479
TI  - Evaluation of candidemia in epidemiology and risk factors among cancer patients
      in a cancer center of China: an 8-year case-control study.
AB  - BACKGROUND: Candidemia is the worldwide life-threaten disease, especially in
      cancer patients. This study was aimed to identify and evaluate the risk factors
      of candidemia in cancer patients, which will prompt the improvement on current
      therapeutic strategies and prognosis. METHODS: A retrospective, case-control
      study was conducted from inpatients of Tianjin Medical University Cancer
      Institute and Hospital, during 2006 to 2013. Analyses were performed between
      cancer patients with candidemia as study case, and patients with bacterial
      bloodstream infections as control. Each case was matched up with two controls,
      for gender and inpatient duration. Candida species, clinical characteristics,
      risk factors and outcomes were reviewed in details. RESULTS: Total number of 80
      cases and 160 controls were enrolled and analyzed in this study. Candida albicans
      was identified as the most prevalent species and account for 55.0% candidemia,
      followed by Candida parapsilosis complex (21.3%), Candida tropicalis (8.8%),
      Candida glabrata complex (7.5%), Candida lusitaniae (3.8%), and Candida famata
      (3.8%). The crude mortality at 30-days of candidemia was up to 30.0%, which is
      significantly higher than bacterial bloodstream infections (p = 0.006).
      Logistical analysis demonstrated that total parenteral nutrition >5 days (p =
      0.036), urinary catheter >2 days (p = 0.001), distant organ metastasis of cancer
      (p = 0.002) and gastrointestinal cancer (p = 0.042) were the independent risk
      factors for candidemia. CONCLUSIONS: Candidemia showed significant higher
      mortality than bacterial bloodstream infections, C. albicans was cited as the
      primary pathogen. Total parenteral nutrition, urinary catheter, distant organ
      metastasis of cancer and gastrointestinal cancer are independent predictors for
      candidemia, this findings provides potential therapeutic targets for improving
      the outcome.

PMID- 28768480
TI  - Internet and social network users' profiles in Renal Transplant Recipients in
      France.
AB  - BACKGROUND: The use of the Internet for searching and sharing health information
      and for health care interactions may have a great potential for Renal Transplant
      Recipients (RTR). This study aims to determine the characteristics associated
      with Internet and social network use in a representative sample of RTR at the
      time of their inclusion in the study. METHODS: Data of this cross-sectional
      design is retrieved from a longitudinal study conducted in five French kidney
      transplant centers in 2011, and included Renal Transplant Recipients aged 18
      years with a functioning graft for at least 1 year. Measures include demographic
      characteristics (age, gender, level of education, employment status, living
      arrangement, having children, invalidity and monthly incomes in the household),
      psycho-social characteristics measured by the perceived social support
      questionnaire, and medical characteristics (previous dialysis treatment, duration
      since transplantation, graft rejection episodes, chronic graft dysfunction,
      health status and comorbidities: neoplasia for the current transplant,
      hypertension, diabetes mellitus, smoking status, BMI > 30 kg/m2 and Charlson
      Comorbidity Index (CCI)). Polytomous linear regression analysis was performed to
      describe the Internet and social network users' profiles, using lack of Internet
      access as the comparison category. RESULTS: Among the 1416 RTR participating in
      the study, 20.1% had no Internet access in the household, 29.4% connected to
      social networks and 50.5% were not connected to social networks. Patients who
      connected the most to the Internet and social networks were younger, male,
      without children, employed, with high monthly incomes in the household, without
      hypertension and having felt a need for an informative or an esteem support.
      CONCLUSION: In our study, the majority of RTR were actively using Internet and
      social networks. Renal transplant units should develop flexible and Web-based
      sources related to transplant information, which will allow a rapid adaptation to
      changes in prevalent practice, improve the health of the patients and reflect
      their preferences.

PMID- 28768481
TI  - PiiL: visualization of DNA methylation and gene expression data in gene pathways.
AB  - BACKGROUND: DNA methylation is a major mechanism involved in the epigenetic state
      of a cell. It has been observed that the methylation status of certain CpG sites
      close to or within a gene can directly affect its expression, either by silencing
      or, in some cases, up-regulating transcription. However, a vertebrate genome
      contains millions of CpG sites, all of which are potential targets for
      methylation, and the specific effects of most sites have not been characterized
      to date. To study the complex interplay between methylation status, cellular
      programs, and the resulting phenotypes, we present PiiL, an interactive gene
      expression pathway browser, facilitating analyses through an integrated view of
      methylation and expression on multiple levels. RESULTS: PiiL allows for specific
      hypothesis testing by quickly assessing pathways or gene networks, where the data
      is projected onto pathways that can be downloaded directly from the online KEGG
      database. PiiL provides a comprehensive set of analysis features that allow for
      quick and specific pattern searches. Individual CpG sites and their impact on
      host gene expression, as well as the impact on other genes present in the
      regulatory network, can be examined. To exemplify the power of this approach, we
      analyzed two types of brain tumors, Glioblastoma multiform and lower grade
      gliomas. CONCLUSION: At a glance, we could confirm earlier findings that the
      predominant methylation and expression patterns separate perfectly by mutations
      in the IDH genes, rather than by histology. We could also infer the IDH mutation
      status for samples for which the genotype was not known. By applying different
      filtering methods, we show that a subset of CpG sites exhibits consistent
      methylation patterns, and that the status of sites affect the expression of key
      regulator genes, as well as other genes located downstream in the same pathways.
      PiiL is implemented in Java with focus on a user-friendly graphical interface.
      The source code is available under the GPL license from
      https://github.com/behroozt/PiiL.git .

PMID- 28768483
TI  - Live-cell calcium imaging of adherent and non-adherent GL261 cells reveals
      phenotype-dependent differences in drug responses.
AB  - BACKGROUND: The tumor-derived GL261 cell line is used as a model for studying
      glioblastoma and other high-grade gliomas, and can be cultured adherently or as
      free-floating aggregates known as neurospheres. These different culture
      conditions give rise to distinct phenotypes, with increased tumorigenicity
      displayed by neurosphere-cultured cells. An important technique for understanding
      GL261 pathobiology is live cell fluorescent imaging of intracellular calcium.
      However, live cell imaging of GL261 neurospheres presents a technical challenge,
      as experimental manipulations where drugs are added to the extracellular media
      cause the cells to move during analysis. Here we present a method to immobilize
      GL261 neurospheres with low melting point agarose for calcium imaging using the
      fluorescent calcium sensor fura-2. METHODS: GL261 cells were obtained from the
      NCI-Frederick Cancer Research Tumor Repository and cultured as adherent cells or
      induced to form neurospheres by placing freshly trypsinized cells into serum-free
      media containing fibroblast growth factor 2, epidermal growth factor, and B-27
      supplement. Prior to experiments, adherent cells were loaded with fura-2 and
      cultured on 8-well chamber slides. Non-adherent neurospheres were first loaded
      with fura-2, placed in droplets onto an 8-well chamber slide, and finally covered
      with a thin layer of low melting point agarose to immobilize the cells.
      Ratiometric pseudocolored images were obtained during treatment with ATP,
      capsaicin, or vehicle control. Cells were marked as responsive if fluorescence
      levels increased more than 30% above baseline. Differences between treatment
      groups were tested using Student's t-tests and one-way ANOVA. RESULTS: We found
      that cellular responses to pharmacological treatments differ based on cellular
      phenotype. Adherent cells and neurospheres both responded to ATP with a rise in
      intracellular calcium. Notably, capsaicin treatment led to robust responses in
      GL261 neurospheres but not adherent cells. CONCLUSIONS: We demonstrate the use of
      low melting point agarose for immobilizing GL261 cells, a method that is broadly
      applicable to any cell type cultured in suspension, including acutely trypsinized
      cells and primary tumor cells. Our results indicate that it is important to
      consider GL261 phenotype (adherent or neurosphere) when interpreting data
      regarding physiological responses to experimental compounds.

PMID- 28768482
TI  - Comparative genomic analysis and characterization of incompatibility group FIB
      plasmid encoded virulence factors of Salmonella enterica isolated from food
      sources.
AB  - BACKGROUND: The degree to which the chromosomal mediated iron acquisition system
      contributes to virulence of many bacterial pathogens is well defined. However,
      the functional roles of plasmid encoded iron acquisition systems, specifically
      Sit and aerobactin, have yet to be determined for Salmonella spp. In a recent
      study, Salmonella enterica strains isolated from different food sources were
      sequenced on the Illumina MiSeq platform and found to harbor the incompatibility
      group (Inc) FIB plasmid. In this study, we examined sequence diversity and the
      contribution of factors encoded on the IncFIB plasmid to the virulence of S.
      enterica. RESULTS: Whole genome sequences of seven S. enterica isolates were
      compared to genomes of serovars of S. enterica isolated from food, animal, and
      human sources. SeqSero analysis predicted that six strains were serovar
      Typhimurium and one was Heidelberg. Among the S. Typhimurium strains, single
      nucleotide polymorphism (SNP)-based phylogenetic analyses revealed that five of
      the isolates clustered as a single monophyletic S. Typhimurium subclade, while
      one of the other strains branched with S. Typhimurium from a bovine source. DNA
      sequence based phylogenetic diversity analyses showed that the IncFIB plasmid
      encoded Sit and aerobactin iron acquisition systems are conserved among bacterial
      species including S. enterica. The IncFIB plasmid was transferred to an IncFIB
      plasmid deficient strain of S. enterica by conjugation. The transconjugant
      SE819::IncFIB persisted in human intestinal epithelial (Caco-2) cells at a higher
      rate than the recipient SE819. Genes of the Sit and aerobactin operons in the
      IncFIB plasmid were differentially expressed in iron-rich and iron-depleted
      growth media. CONCLUSIONS: Minimal sequence diversity was detected in the Sit and
      aerobactin operons in the IncFIB plasmids present among different bacterial
      species, including foodborne Salmonella strains. IncFIB plasmid encoded factors
      play a role during infection under low-iron conditions in host cells.

PMID- 28768484
TI  - Genome-wide identification of soybean microRNA responsive to soybean cyst
      nematodes infection by deep sequencing.
AB  - BACKGROUND: The soybean cyst nematode (SCN), Heterodera glycines, is one of the
      most devastating diseases limiting soybean production worldwide. It is known that
      small RNAs, including microRNAs (miRNAs) and small interfering RNAs (siRNAs),
      play important roles in regulating plant growth and development, defense against
      pathogens, and responses to environmental changes. RESULTS: In order to
      understand the role of soybean miRNAs during SCN infection, we analyzed 24 small
      RNA libraries including three biological replicates from two soybean cultivars
      (SCN susceptible KS4607, and SCN HG Type 7 resistant KS4313N) that were grown
      under SCN-infested and -noninfested soil at two different time points (SCN
      feeding establishment and egg production). In total, 537 known and 70 putative
      novel miRNAs in soybean were identified from a total of 0.3 billion reads
      (average about 13.5 million reads for each sample) with the programs of Bowtie
      and miRDeep2 mapper. Differential expression analyses were carried out using
      edgeR to identify miRNAs involved in the soybean-SCN interaction. Comparative
      analysis of miRNA profiling indicated a total of 60 miRNAs belonging to 25
      families that might be specifically related to cultivar responses to SCN.
      Quantitative RT-PCR validated similar miRNA interaction patterns as sequencing
      results. CONCLUSION: These findings suggest that miRNAs are likely to play key
      roles in soybean response to SCN. The present work could provide a framework for
      miRNA functional identification and the development of novel approaches for
      improving soybean SCN resistance in future studies.

PMID- 28768485
TI  - A systematic review of genetic mutations in pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a group of vascular diseases
      that produce right ventricular dysfunction, heart failure syndrome, and death.
      Although the majority of patients appear idiopathic, accumulated research work
      combined with current sequencing technology show that many gene variants could be
      an important component of the disease. However, current guidelines, clinical
      practices, and available gene panels focus the diagnosis of PAH on a relatively
      low number of genes and variants associated with the bone morphogenic proteins
      and transforming Growth Factor-beta pathways, such as the BMPR2, ACVRL1, CAV1,
      ENG, and SMAD9. METHODS: To provide an expanded view of the genes and variants
      associated with PAH, we performed a systematic literature review. Facilitated by
      a web tool, we classified, curated, and annotated most of the genes and PubMed
      abstracts related to PAH, in which many of the mutations and variants were not
      annotated in public databases such as ClinVar from NCBI. The gene list generated
      was compared with other available tests. RESULTS: Our results reveal that there
      is genetic evidence for at least 30 genes, of which 21 genes shown specific
      mutations. Most of the genes are not covered by current available genetic panels.
      Many of these variants were not annotated in the ClinVar database and a mapping
      of these mutations suggest that next generation sequencing is needed to cover all
      mutations found in PAH or related diseases. A pathway analysis of these genes
      indicated that, in addition to the BMP and TGFbeta pathways, there was
      connections with the nitric oxide, prostaglandin, and calcium homeostasis
      signalling, which may be important components in PAH. CONCLUSION: Our systematic
      review proposes an expanded gene panel for more accurate characterization of the
      genetic incidence and risk in PAH. Their usage would increase the knowledge of
      PAH in terms of genetic counseling, early diagnosis, and potential prognosis of
      the disease.

PMID- 28768486
TI  - Lumbar puncture as possible cause of sudden paradoxical herniation in patient
      with previous decompressive craniectomy: report of two cases.
AB  - BACKGROUND: Lumbar puncture is often used for the diagnosis and treatment of
      subarchnoid hemorrhage, infection of Cerebro-spinal Fluid (CSF), hydrocephalus in
      neurosurgery department patients. It is general that paradoxical herniation
      followed by lumbar puncture is quite rare in decompressive craniectomy cases; the
      related reports are very few. Moreover, most of the paradoxical herniation cases
      are chronic, which often occur weeks or even months after the lumbar puncture, to
      date, barely no reports on the acute onset paradoxical herniation have been
      found. CASE PRESENTATION: Two traumatic brain injury patients with decompressive
      craniectomy (DC) and hydrocephalus suffered from a sudden paradoxical herniation
      after lumbar puncture. The symptoms of herniation were improved by treated with
      Trendelenburg position and rapid intravenous infusion. CONCLUSIONS: Lumbar
      puncture may have a potential risk of inducing sudden paradoxical herniation in
      patients with DC. CSF drainage during lumbar puncture should be in small volume
      for patients with DC. Once a paradoxical herniation occurs after lumbar puncture,
      an immediate Trendelenburg position and rapid intravenous infusion treatment may
      be effective.

PMID- 28768487
TI  - Developing quality indicators for assessing quality of birth centre care: a mixed
      methods study.
AB  - BACKGROUND: Birth centres are described as settings where women with
      uncomplicated pregnancies can give birth in a home-like environment assisted by
      midwives and maternity care assistants. If complications arise or threaten, the
      woman is referred to a maternity unit of a hospital where an obstetrician will
      take over responsibility. In the last decade, a number of new birth centres have
      been established in the Netherlands, based on the assumption that birth centres
      provide better quality of care since they offer a better opportunity for more
      integrated care than the existing system with independent primary and secondary
      care providers. At present, there is no evidence for this assumption. The Dutch
      Birth Centre Study is designed to present evidence-based recommendations for
      organization and functioning of future birth centres in the Netherlands. A
      necessary first step in this evaluation is the development of indicators for
      measuring the quality of the care delivered in birth centres in the Netherlands.
      The aim of this study is to identify a comprehensive set of structure and process
      indicators to assess quality of birth centre care. METHODS: We used mixed methods
      to develop a set of structure and process quality indicators for evaluating birth
      centre care. Beginning with a literature review, we developed an exhaustive list
      of determinants. We then used a Delphi study to narrow this list, calling on
      experts to rate the determinants for relevance and feasibility. A
      multidisciplinary expert panel of 63 experts, directly or indirectly involved
      with birth centre care, was invited to participate. RESULTS: A panel of 42
      experts completed two Delphi rounds rating determinants of the quality of birth
      centre care based on their relevance (to the setting) and feasibility (of use). A
      set of 30 determinants for structure and process quality indicators was
      identified to assess the quality of birth centre care in the Netherlands.
      CONCLUSIONS: We identified 30 determinants for structure and process quality
      indicators concerning birth centre care. This set will be validated during the
      evaluation of birth centres in the Dutch Birth Centre Study.

PMID- 28768489
TI  - Improved anticancer drug response prediction in cell lines using matrix
      factorization with similarity regularization.
AB  - BACKGROUND: Human cancer cell lines are used in research to study the biology of
      cancer and to test cancer treatments. Recently there are already some large
      panels of several hundred human cancer cell lines which are characterized with
      genomic and pharmacological data. The ability to predict drug responses using
      these pharmacogenomics data can facilitate the development of precision cancer
      medicines. Although several methods have been developed to address the drug
      response prediction, there are many challenges in obtaining accurate prediction.
      METHODS: Based on the fact that similar cell lines and similar drugs exhibit
      similar drug responses, we adopted a similarity-regularized matrix factorization
      (SRMF) method to predict anticancer drug responses of cell lines using chemical
      structures of drugs and baseline gene expression levels in cell lines.
      Specifically, chemical structural similarity of drugs and gene expression profile
      similarity of cell lines were considered as regularization terms, which were
      incorporated to the drug response matrix factorization model. RESULTS: We first
      demonstrated the effectiveness of SRMF using a set of simulation data and
      compared it with two typical similarity-based methods. Furthermore, we applied it
      to the Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line
      Encyclopedia (CCLE) datasets, and performance of SRMF exceeds three state-of-the
      art methods. We also applied SRMF to estimate the missing drug response values in
      the GDSC dataset. Even though SRMF does not specifically model mutation
      information, it could correctly predict drug-cancer gene associations that are
      consistent with existing data, and identify novel drug-cancer gene associations
      that are not found in existing data as well. SRMF can also aid in drug
      repositioning. The newly predicted drug responses of GDSC dataset suggest that
      mTOR inhibitor rapamycin was sensitive to non-small cell lung cancer (NSCLC), and
      expression of AK1RC3 and HINT1 may be adjunct markers of cell line sensitivity to
      rapamycin. CONCLUSIONS: Our analysis showed that the proposed data integration
      method is able to improve the accuracy of prediction of anticancer drug responses
      in cell lines, and can identify consistent and novel drug-cancer gene
      associations compared to existing data as well as aid in drug repositioning.

PMID- 28768488
TI  - Success/failure condition influences attribution of control, negative affect, and
      shame among patients with depression in Singapore.
AB  - BACKGROUND: There remains a paucity of research on control attribution and
      depression within Asian populations. This study examines: (1) Success/Failure
      condition as a moderator between depression and negative affect or shame, and (2)
      differences in control attribution between patients with depression and healthy
      controls in Singapore. METHODS: Seventy one patients with depression and 71
      healthy controls went through a digit-span memory task where they were randomized
      into either the Success or Failure condition. Participants in the Success
      condition had to memorize and recall 5-digit strings, while participants in the
      Failure condition did the same for 12-digit strings. They then completed self
      report measures of negative affect, shame, and attribution of control. One-way
      ANCOVA was performed to examine task condition as a moderator of association
      between mental health status and post-task negative affect or shame. Test of
      simple effects was carried out on significant interactions. Sign test and Mann
      Whitney U test were employed to investigate differences in attribution of
      control. RESULTS: Mental health status and Success/Failure condition had
      significant effects on reported negative affect and shame. Healthy controls
      reported less post-task negative affect and shame in the Success than in the
      Failure condition while patients with depression reported similar levels of post
      task negative affect and shame in both conditions. However, these differences
      were not significant in the test of simple effects. In addition, healthy controls
      felt a stronger sense of personal control in success than in failure and were
      more likely to blame external factors in failure than in success. Conversely,
      patients with depression were more inclined to credit external factors in success
      than in failure and ascribed greater personal control in failure than in success.
      CONCLUSION: The results suggest that successful conditions may not necessitate
      the reduction of negative affect in Asians with depression, indicating possible
      cultural variation in affective states as a result of control attribution and the
      importance of attending to these variations in designing psychological
      intervention for Asians. Further studies are required to gather more evidence on
      control attributions in different contexts and study other cognitive mechanisms
      related to depression in the Asian population.

PMID- 28768490
TI  - Lymphocyte count or percentage: which can better predict the prognosis of
      advanced cancer patients following palliative care?
AB  - BACKGROUND: The lymphocytes played an important role in the natural history of
      cancer. The aim of this study was to explore the prognostic value of lymphocyte
      count and percentage for survival in advanced cancer patients receiving
      palliative care. METHODS: A retrospective review of clinicopathological data from
      378 consecutive advanced cancer patients and 106 extended follow-up patients
      treated with palliative care was conducted. Kaplan-Meier curves and multivariate
      cox regression analyses were used to evaluate the relationships of peripheral
      lymphocyte count (LC) and lymphocyte to white blood cell ratio (LWR) with overall
      survival (OS). RESULTS: The median values for pretreatment LC and LWR were 1.1
      (IQR, 0.8 ~ 1.5 * 109/L) and 0.138 (IQR, 0.086 ~ 0.208). The median survival
      times across LWR quartiles were 19, 47, 79, and 101 days (P < 0.001).
      Multivariate analysis indicated that patients in the highest quartiles of LC and
      LWR had an HR of 1.082 (95% CI 0.777 ~ 1.506, P = 0.642) and 0.466 (95% CI 0.328
      ~ 0.661, P < 0.001), respectively, compared with patients in the lowest
      quartiles. Furthermore, only the dynamic changes of LWR were confirmed as an
      independent prognostic factor for overall survival during the follow-up (HR =
      0.396, 95% CI 0.243 ~ 0.668; P = 0.001), as were primary tumor site and ECOG. No
      effect was observed for the dynamic changes of LC. CONCLUSIONS: Our findings
      demonstrate that measurement of the dynamic changes of LWR prior to treatment and
      during follow-up may represent a simple and new powerful prognostic factor for
      patients with advanced cancer, unlike measurement of LC. As a bedside marker of
      immune status, the prognostic role of LWR should be further evaluated in
      prospective studies.

PMID- 28768491
TI  - Succinate dehydrogenase deficiency in a PDGFRA mutated GIST.
AB  - BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor mutually
      exclusive gain of function mutations in the receptor tyrosine kinase (RTK) KIT
      (70-80%) or in the related receptor PDGFRA (~10%). These GISTs generally respond
      well to therapy with the RTK inhibitor imatinib mesylate (IM), although initial
      response is genotype-dependent. An alternate mechanism leading to GIST
      oncogenesis is deficiency in the succinate dehydrogenase (SDH) enzyme complex
      resulting from genetic or epigenetic inactivation of one of the four SDH subunit
      genes (SDHA, SDHB, SDHC, SDHD, collectively referred to as SDHX). SDH loss of
      function is generally seen only in GIST lacking RTK mutations, and SDH-deficient
      GIST respond poorly to imatinib therapy. METHODS: Tumor and normal DNA from a
      GIST case carrying the IM-resistant PDGFRA D842V mutation was analyzed by whole
      exome sequencing (WES) to identify additional potential targets for therapy. The
      tumors analyzed were separate recurrences following progression on imatinib,
      sunitinib, and the experimental PDGFRA inhibitor crenolanib. Tumor sections from
      the GIST case and a panel of ~75 additional GISTs were subjected to
      immunohistochemistry (IHC) for the SDHB subunit. RESULTS: Surprisingly, a
      somatic, loss of function mutation in exon 4 of the SDHB subunit gene
      (c.291_292delCT, p.I97Mfs*21) was identified in both tumors. Sanger sequencing
      confirmed the presence of this inactivating mutation, and IHC for the SDHB
      subunit demonstrated that these tumors were SDH-deficient. IHC for the SDHB
      subunit across a panel of ~75 GIST cases failed to detect SDH deficiency in other
      GISTs with RTK mutations. CONCLUSIONS: This is the first reported case of a
      PDGFRA mutant GIST exhibiting SDH-deficiency. A brief discussion of the relevant
      GIST literature is included.

PMID- 28768492
TI  - The effect of youth assertive community treatment: a systematic PRISMA review.
AB  - BACKGROUND: During the past decades deinstitutionalisation policies have led to a
      transition from inpatient towards community mental health care. Many European
      countries implement Assertive Community Treatment (ACT) as an alternative for
      inpatient care for "difficult to reach" children and adolescents with severe
      mental illness. ACT is a well-organized low-threshold treatment modality;
      patients are actively approached in their own environment, and efforts are
      undertaken to strengthen the patient's motivation for treatment. The assumption
      is that ACT may help to avoid psychiatric hospital admissions, enhance cost
      effectiveness, stimulate social participation and support, and reduce stigma. ACT
      has been extensively investigated in adults with severe mental illness and
      various reviews support its effectiveness in this patient group. However, to date
      there is no review available regarding the effectiveness of youth-ACT. It is
      unknown whether youth-ACT is as effective as it is in adults. This review aims to
      assess the effects of youth-ACT on severity of psychiatric symptoms, general
      functioning, and psychiatric hospital admissions. METHOD: A systematic literature
      search was conducted in PubMed, Cochrane Library, PsychINFO and CINAHL published
      up to March 2017. To assess methodological quality of the included studies, the
      Oxford Centre of Evidence-Based Medicine grading system was used. RESULTS:
      Thirteen studies were included in this review. There are indications that youth
      ACT is effective in reducing severity of psychiatric symptoms, improving general
      functioning, and reducing duration and frequency of psychiatric hospital
      admissions. CONCLUSIONS: The current literature on youth-ACT is limited but
      promising. There are indications that youth-ACT is effective in reducing severity
      of psychiatric symptoms, improving general functioning, and reducing duration and
      frequency of psychiatric hospital admissions. The effect of youth-ACT may be
      comparable with the effect of ACT in adults. Similar as in adult ACT, the studies
      on youth-ACT found effects that vary from small to large. Randomized experimental
      research designs are needed to further corroborate effectiveness.

PMID- 28768493
TI  - Randomized controlled pilot trial of supportive text messages for patients with
      depression.
AB  - BACKGROUND: Depression is projected to be the primary cause of disability
      worldwide by 2030. In a recent survey, the most commonly cited unmet need among
      42.4% of depressed Albertans was the lack of sufficient, accessible, and
      affordable counselling. Our aim was to test the efficacy of a supportive text
      messaging mobile health intervention in improving treatment outcomes in depressed
      patients. METHODS: We performed a single-rater-blinded randomized trial involving
      73 patients with Major Depressive Disorder. Patients in the intervention group (n
      = 35) received twice-daily supportive text messages for 3 months while those in
      the control group (n = 38) received a single text message every fortnight
      thanking them for participating in the study. The primary outcome of this study
      was: "Mean changes in the BDI scores from baseline". RESULTS: After adjusting for
      baseline BDI scores, a significant difference remained in the 3 month mean BDI
      scores between the intervention and control groups: (20.8 (SD = 11.7) vs. 24.9
      (SD = 11.5), F (1, 60) = 4.83, p = 0.03, etap2 = 0.07). The mean difference in
      the BDI scores change was significant with an effect size (Cohen's d) of 0.67.
      Furthermore, after adjusting for baseline scores, a significant difference
      remained in the 3 month mean self-rated VAS scores (EQ-5D-5 L scale) between the
      intervention and control groups, 65.7 (SD = 15.3) vs. 57.4 (SD = 22.9), F (1, 60)
      =4.16, p = 0.05, etap2 = 0.065. The mean difference in change mean self-rated VAS
      scores was also statistically significant with an effect size (Cohen's d) of
      0.51. CONCLUSIONS: Our findings suggest that supportive text messages are a
      potentially useful psychological intervention for depression, especially in
      underserved populations. Further studies are needed to explore the implications
      of our findings in larger clinical samples. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02327858 . Registered 24 December 2014.

PMID- 28768494
TI  - Socio-cognitive correlates of intention to use Toombak: a cross-sectional study
      among students (13-16 years) in Khartoum State, Sudan.
AB  - BACKGROUND: Toombak is a form of smokeless tobacco, locally made and consumed in
      Sudan. It is associated with a number of health hazards, particularly oral
      cancer. This study was set out to assess the prevalence and socio-demographic
      distribution of its use, and to explore the socio-cognitive factors affecting the
      intention to use Toombak among secondary school students in Khartoum State,
      Sudan. METHODS: A cross-sectional school-based study was conducted in 2013-2014
      where schools were randomly selected using a one-stage stratified sampling
      procedure. The sample size was calculated to consist of 1526 students. Data were
      collected through a self-administered questionnaire, which contained some
      cognitive constructs; information received, social image, attitudes, normative
      social influence, accessibility to Toombak, socio-demographics and Toombak use
      related variables. RESULTS: A total of 1670 secondary school students
      participated in the study. More than half of them 53.4% were <15-years-old and
      53.6% were females. Only 5.3% of the students reported intention to use Toombak.
      Among the students 10.9% were ever Toombak users, 81.6% reported a positive
      attitude towards its use and 60.7% had received information about its harmful
      effects. A total of 72.6% reported normative social influence towards using
      Toombak and 62.5% perceived a negative social image attached to its use. Most of
      the students, 70.8% reported exposure to anti-Toombak information, 41.8%
      confirmed exposure to Toombak advertisement and 87.5% reported indirect access to
      its sale. Younger students reported ever use of Toombak less frequently than
      their older counterparts (38.4% versus 61.6%), p < 0.001. Males reported ever use
      of Toombak more frequently than did females (74.3% versus 25.7%), p < 0.001.
      According to the regression model, individuals who perceived a positive social
      image of Toombak users and had past experience were more likely to intend to its
      use. CONCLUSIONS: The present study suggested that the prevalence of Toombak use
      among Sudanese secondary school students is low and that male and older students
      are more frequent users. Students' decision to use Toombak was based upon past
      experience with Toombak use and the social image attached to its use. Easy access
      to Toombak and encouragement from friends and classmates were among the factors
      which support intention to use Toombak but only in the unadjusted analyses.

PMID- 28768495
TI  - Exploring the determinants of health and wellbeing in communities living in
      proximity to coal seam gas developments in regional Queensland.
AB  - BACKGROUND: There is some concern that coal seam gas mining may affect health and
      wellbeing through changes in social determinants such as living and working
      conditions, local economy and the environment. The onward impact of these
      conditions on health and wellbeing is often not monitored to the same degree as
      direct environmental health impacts in the mining context, but merits attention.
      This study reports on the findings from a recurrent theme that emerged from
      analysis of the qualitative component of a comprehensive Health Needs Assessment
      (HNA) conducted in regional Queensland: that health and wellbeing of communities
      was reportedly affected by nearby coal seam gas (CSG) development beyond direct
      environmental impacts. METHODS: Qualitative analysis was initially completed
      using the Framework Method to explore key themes from 11 focus group discussions,
      19 in-depth interviews, and 45 key informant interviews with health and wellbeing
      service providers and community members. A key theme emerged from the analysis
      that forms the basis of this paper. This study is part of a larger comprehensive
      HNA involving qualitative and quantitative data collection to explore the health
      and wellbeing needs of three communities living in proximity to CSG development
      in regional Queensland, Australia. RESULTS: Communities faced social, economic
      and environmental impacts from the rapid growth of CSG development, which were
      perceived to have direct and indirect effects on individual lifestyle factors
      such as alcohol and drug abuse, family relationships, social capital and mental
      health; and community-level factors including social connectedness, civic
      engagement and trust. CONCLUSIONS: Outer regional communities discussed the
      effects of mining activity on the fabric of their town and community, whereas the
      inner regional community that had a longer history of industrial activity
      discussed the impacts on families and individual health and wellbeing. The
      findings from this study may inform future health service planning in regions
      affected by CSG in the development /construction phase and provide the mining
      sector in regional areas with evidence from which to develop social
      responsibility programs that encompass health, social, economic and environmental
      assessments that more accurately reflect the needs of the affected communities.

PMID- 28768496
TI  - Transcriptomic analysis of the differentiating ovary of the protogynous ricefield
      eel Monopterus albus.
AB  - BACKGROUND: The ricefield eel is a protogynous hermaphroditic Synbranchiform
      species that changes sex naturally from female to male, which offers an
      interesting model for studying gonadal (particularly ovarian) differentiation in
      vertebrates. In the present study, transcriptome sequencing of the gonad of
      ricefield eel larvae was performed to explore the molecular mechanisms underlying
      the ovarian differentiation and development. RESULTS: A total of 301,267,988
      clean reads were generated from cDNA libraries of gonadal tissues of ricefield
      eel larvae at 6, 9, 12, and 20 days post hatching (dph), which contained
      undifferentiated gonads, differentiating ovaries, ovaries with oogonia, and
      ovaries with meiotic oocytes, respectively. De-novo assembly of all the clean
      reads generated a total of 265,896 unigenes with a mean size of 720 bp and a N50
      of 1107 bp. RT-qPCR analysis of the developmental expression of 13 gonadal
      development-related functional genes indicated that RNA-seq data are reliable.
      Transcriptome data suggest that high expression of female development-related
      genes and low expression of male development-related genes in the early gonads of
      ricefield eel larvae participate in the cascade of sex differentiation leading to
      the final female phenotype. The contrasting expression patterns of genes involved
      in retinoid acid (RA) synthesis and degradation might result in peak production
      of RA at 12 dph in the gonad of ricefield eel larvae, and induce molecular events
      responsible for the initiation of meiosis before the meiotic signs could be
      observed at 20 dph. In addition, only stra6 but not stra8 could be identified in
      gonadal transcriptome data of ricefield eel larvae, and the expression pattern of
      stra6 paralleled those of genes involved in RA synthesis, suggesting that stra6
      may be a downstream target of RA and play a role in RA metabolism and/or meiotic
      initiation in the gonad of ricefield eel larvae. CONCLUSIONS: The present study
      depicted the first large-scale RNA sequencing of the gonad of ricefield eel
      larvae, and identified many important functional genes, GO terms and KEGG
      pathways involved in gonadal development and germ cell meiosis. Results of the
      present study will facilitate future study on the ovarian differentiation of
      ricefield eels and other teleosts as well.

PMID- 28768497
TI  - Prevalence and associated factors of alexithymia among adult prisoners in China:
      a cross-sectional study.
AB  - BACKGROUND: Prison is an extremely stressful environment and prisoners have an
      increasing risk of suffering from alexithymia. Therefore, this study aims to
      investigate the prevalence and associated factors of alexithymia among prisoners
      in China. METHODS: A cross-sectional study was conducted in five main jails of
      the district of Zhejiang province in China, and a total of 1705 adult prisoners
      ultimately took part in the study. Toronto Alexithymia Scale, Childhood Trauma
      Questionnaire, Beck Depression Inventory, Beck Anxiety Inventory, Beck
      Hopelessness Scale and several short demographic questions were applied. RESULTS:
      Over 30% of prisoners were classified as alexithymics and as high as 96.2% of
      prisoners suffered from at least one traumatic experience in their childhood,
      meanwhile, 81.5%, 53.4% and 85.8% were found to be positive for depression,
      anxiety and hopelessness symptoms respectively. Education, childhood trauma,
      negative emotional symptoms including depression, anxiety and hopelessness of the
      respondents, were negatively or positively associated with alexithymia among
      prisoners. CONCLUSIONS: The results indicated that high prevalence of alexithymia
      among prisoners is linked with their level of education, experience of childhood
      trauma and symptoms of negative emotions. Accordingly, the findings in our study
      can be used for prevention and intervention of alexithymia among prisoners.

PMID- 28768498
TI  - Effect of volatile compounds produced by Ralstonia solanacearum on plant growth
      promoting and systemic resistance inducing potential of Bacillus volatiles.
AB  - BACKGROUND: Microbial volatiles play an expedient role in the agricultural
      ecological system by enhancing plant growth and inducing systemic resistance
      against plant pathogens, without causing hazardous effects on the environment. To
      explore the effects of VOCs of Ralstonia solanacearum TBBS1 (Rs) on tobacco plant
      growth and on plant growth promoting efficiency of VOCs produced by Bacillus
      subtilis SYST2, experiments were conducted both in vitro and in planta. RESULTS:
      The VOCs produced by SYST2 significantly enhanced the plant growth and induced
      the systemic resistance (ISR) against wilt pathogen Rs in all experiments. The
      SYST2-VOCs significantly increased PPO and PAL activity and over-expressed the
      genes relating to expansin, wilt resistance, and plant defense while repressed
      the genes relating to ethylene production. More interestingly, VOCs produced by
      pathogen, Rs had no significant effect on plant growth; however, Rs-VOCs
      decreased the growth promoting potential of SYST2-VOCs when plants were exposed
      to VOCs produced by both SYST2 and Rs. The co-culture of SYST2 and Rs revealed
      that they inhibited the growth of each other; however, the inhibition of Rs by
      SYST2-VOCs appeared to be greater than that of SYST2 by Rs-VOCs. CONCLUSION: Our
      findings provide new insights regarding the interaction among SYST2-VOCs, Rs-VOCs
      and plant, resulting in growth promotion and induced systemic resistance against
      the bacterial wilt pathogen Rs. This is the first report of the effect of VOCs
      produced by pathogenic microorganism on plant growth and on plant growth
      promoting and systemic resistance-inducing potential of PGPR strain SYST2.

PMID- 28768499
TI  - Simultaneous primary invasive cutaneous aspergillosis in two preterm twins: case
      report and review of the literature.
AB  - BACKGROUND: Primary invasive cutaneous aspergillosis is a rare fungal infection
      that occurs mostly in immunocompromised patients. Newborns of very low birth
      weight present a high risk for this type of infection due to an immaturity of the
      cutaneous barrier and of the immune system. CASE PRESENTATION: We describe here a
      case of simultaneous invasive cutaneous aspergillosis in two preterm twins. Two
      male preterm bichorionic biamniotic twins (A & B) were born at a general hospital
      by spontaneous normal delivery at 24 weeks and 6 days of gestation. They were
      transferred to our hospital where they receive surfactant, antibiotics and
      hydrocortisone. Six days later, twin A showed greenish lesions in the umbilical
      region. The spectrum of antibiotic therapy was broadened and fluconazole was
      added. The umbilical catheters of the two twins were removed and replaced by
      epicutaneo-cava venous catheters and the cultures were positive for Aspergillus
      fumigatus. Fluconazole was replaced in both twins by liposomal amphotericin B and
      the incubators were changed. The serum galactomannan was also positive for both
      twins. At day 10, yellowish lesions appeared in the abdominal region in twin B.
      He died on day 18 following complications related to his prematurity. Concerning
      the twin A, serum galactomannan was negative on day 30; liposomal amphotericin B
      was stopped 1 week later, with a relay by econazole (cream). His condition
      improved and on day 66 he was transferred for follow-up at the general hospital
      where he was born. CONCLUSION: The source of contamination by A. fumigatus was
      not identified, but other similar cases from the literature include construction
      work at or near the hospital, oximeter sensors, latex finger stalls, non-sterile
      gloves, humidifying chambers of incubators, bedding and adhesive tapes. The skin
      fragility of preterm newborns is an excellent potential entry point for
      environmental fungal infections. These cases highlight the importance of
      suspecting primary cutaneous aspergillosis in extremely low birth weight neonates
      with rapidly progressive necrotic lesions.

PMID- 28768500
TI  - Long term safety and tolerability of Tafluprost 0.0015% vs Timolol 0.1%
      preservative-free in ocular hypertensive and in primary open-angle glaucoma
      patients: a cross sectional study.
AB  - BACKGROUND: The effects of preservatives of antiglaucoma medications on corneal
      surface and tear function have been widely shown in literature; it's not the same
      as regards the active compounds themselves. The purpose of our study was to
      compare Ocular Surface Disease (OSD) signs and symptoms of Tafluprost 0.0015%
      versus preservative free (PF) Timolol 0.1% eyedrops in ocular hypertensive (OH)
      and in primary open-angle glaucoma (POAG) patients. METHODS: A cross-sectional
      study included patients in monotherapy for at least 36 months with Tafluprost
      0.0015% (27) or PF Timolol 0.1% (24) and 20 healthy age and sex-matched
      volunteers. All subjects underwent clinical tests (Schirmer I and break-up time),
      in vivo confocal microscopy (IVCM) and were surveyed using Ocular Surface Disease
      Index (OSDI) and Glaucoma Symptoms Scale (GSS) questionnaires. The groups were
      compared with ANOVA, Kruskal-Wallis test, t-test, Mann-Whitney test and
      Bonferroni's adjustment of p-values. RESULTS: No significant differences were
      found in questionnaires scores, clinical tests, IVCM variables between therapy
      groups. Tafluprost 0.0015% group showed significantly higher OSDI score, basal
      epithelial cells density, stromal reflectivity, sub-basal nerves tortuosity (p =
      0.0000, 0.037, 0.006, 0.0000) and less GSS score, number of sub-basal nerves (p =
      0.0000, 0.037) than controls but similar clinical tests results (p > 0.05). PF
      Timolol group had significantly higher OSDI score, basal epithelial cells
      density, stromal reflectivity and sub-basal nerve tortuosity (p = 0.000, 0.014,
      0.008, 0.002), less GSS score, BUT and number of sub-basal nerves (p = 0.0000,
      0.026, 0.003) than controls. CONCLUSIONS: Compared to PF Timolol 0.1%, Tafluprost
      0.0015% showed similar safety with regards to tear function and corneal status
      and a similar tolerability profile. Both therapy groups show some alterations in
      corneal microstructure but no side effects on tear function except for an
      increased tear instability in PF Timolol 0.1% group. Ophtalmologists should be
      aware that even PF formulations may lead to a mild ocular surface impairment.

PMID- 28768502
TI  - Preventing musculoskeletal injuries among recreational adult volleyball players:
      design of a randomised prospective controlled trial.
AB  - BACKGROUND: Both acute and overuse injuries are common among recreational
      volleyball players, especially finger/wrist, ankle, shoulder and knee injuries.
      Consequently, an intervention ('VolleyVeilig') was developed to prevent or reduce
      the occurrence of finger/wrist, shoulder, knee and ankle injuries among
      recreational volleyball players. This article describes the design of a study
      evaluating the effectiveness of the developed intervention on the one-season
      occurrence of finger/wrist, shoulder, knee and ankle injuries among recreational
      adult volleyball players. METHODS: A randomized prospective controlled trial with
      a follow-up period of one volleyball season will be conducted. Participants will
      be healthy recreational adult volleyball players (18 years of age or older)
      practicing volleyball (training and/or match) at least twice a week. The
      intervention ('VolleyVeilig') consists of a warm-up program based on more than 50
      distinct exercises (with different variations and levels). The effect of the
      intervention programme on the occurrence of injuries will be compared to
      volleyball as usual. Outcome measures will be incidence of acute injury
      (expressed as number of injuries per 1000 h of play) and prevalence of overuse
      injuries (expressed as percentage). DISCUSSION: This study will be one of the
      first randomized prospective controlled trials evaluating the effectiveness of an
      intervention on the occurrence of both acute and overuse injuries among
      recreational adult volleyball players. Outcome of this study could possibly lead
      to the nationwide implementation of the intervention in all volleyball clubs in
      The Netherlands, ultimately resulting in less injuries. TRIAL REGISTRATION: Dutch
      Trial Registration NTR6202 , registered February 1st 2017. PROTOCOL: Version 3,
      February 2017.

PMID- 28768501
TI  - Hybrid clone cells derived from human breast epithelial cells and human breast
      cancer cells exhibit properties of cancer stem/initiating cells.
AB  - BACKGROUND: The biological phenomenon of cell fusion has been associated with
      cancer progression since it was determined that normal cell * tumor cell fusion
      derived hybrid cells could exhibit novel properties, such as enhanced
      metastatogenic capacity or increased drug resistance, and even as a mechanism
      that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been
      proposed as cancer cells that exhibit stem cell properties, including the ability
      to (re)initiate tumor growth. METHODS: Five M13HS hybrid clone cells, which
      originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human
      breast epithelial cells and HS578T-Hyg human breast cancer cells, and their
      parental cells were analyzed for expression of stemness and EMT-related marker
      proteins by Western blot analysis and confocal laser scanning microscopy. The
      frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed
      fluorescent dye. Concurrently, the cells' colony forming capabilities as well as
      the cells' abilities to form mammospheres were investigated. The migratory
      activity of the cells was analyzed using a 3D collagen matrix migration assay.
      RESULTS: M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which
      were differently expressed in parental cells. A variation in the ALDH1-positive
      putative stem cell population was observed among the five hybrids ranging from
      1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all
      five hybrid clone cells possessed increased but also unique colony formation and
      mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the
      highest colony formation capacity and second highest mammosphere formation
      capacity of all hybrids, whereby the mean diameter of the mammospheres was
      comparable to the parental cells. In contrast, the largest mammospheres
      originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere
      formation capacity was comparable to the parental breast cancer cells. All M13HS
      hybrid clones exhibited a mesenchymal phenotype and, with the exception of one
      hybrid clone, responded to EGF with an increased migratory activity. CONCLUSION:
      Fusion of human breast epithelial cells and human breast cancer cells can give
      rise to hybrid clone cells that possess certain CS/IC properties, suggesting that
      cell fusion might be a mechanism underlying how tumor cells exhibiting a CS/IC
      phenotype could originate.

PMID- 28768503
TI  - Comparison of low density and high density pedicle screw instrumentation in Lenke
      1 adolescent idiopathic scoliosis.
AB  - BACKGROUND: The correlation between implant density and deformity correction has
      not yet led to a precise conclusion in adolescent idiopathic scoliosis (AIS). The
      aim of this study was to evaluate the effects of low density (LD) and high
      density (HD) pedicle screw instrumentation in terms of the clinical, radiological
      and Scoliosis Research Society (SRS)-22 outcomes in Lenke 1 AIS. METHODS: We
      retrospectively reviewed 62 consecutive Lenke 1 AIS patients who underwent
      posterior spinal arthrodesis using all-pedicle screw instrumentation with a
      minimum follow-up of 24 months. The implant density was defined as the number of
      screws per spinal level fused. Patients were then divided into two groups
      according to the average implant density for the entire study. The LD group (n =
      28) had fewer than 1.61 screws per level, while the HD group (n = 34) had more
      than 1.61 screws per level. The radiographs were analysed preoperatively,
      postoperatively and at final follow-up. The perioperative and SRS-22 outcomes
      were also assessed. Independent sample t tests were used between the two groups.
      RESULTS: Comparisons between the two groups showed no significant differences in
      the correction of the main thoracic curve and thoracic kyphosis, blood
      transfusion, hospital stay, and SRS-22 scores. Compared with the HD group, there
      was a decreased operating time (278.4 vs. 331.0 min, p = 0.004) and decreased
      blood loss (823.6 vs. 1010.9 ml, p = 0.048), pedicle screws needed (15.1 vs.
      19.6, p < 0.001), and implant costs ($10,191.0 vs. $13,577.3, p = 0.003) in the
      LD group. CONCLUSIONS: Both low density and high density pedicle screw
      instrumentation achieved satisfactory deformity correction in Lenke 1 AIS
      patients. However, the operating time and blood loss were reduced, and the
      implant costs were decreased with the use of low screw density constructs.

PMID- 28768504
TI  - Geographic Variations and Time Trends in Cancer Treatments in Taiwan.
AB  - BACKGROUND: Targeted therapies have become important treatment options for cancer
      care in many countries. This study aimed to examine recent trends in utilization
      of antineoplastic drugs, particularly the use of targeted therapies for treatment
      of cancer, by geographic region in Taiwan (northern, midwestern, southern, and
      eastern regions and the outer islands). METHODS: This was a retrospective
      observational study of antineoplastic agents using 2009-2012 quarterly claims
      data from Taiwan's National Health Insurance Research Database. Yearly market
      shares by prescription volume and costs for targeted therapies among total
      antineoplastic agents by region were estimated. We used multivariate regression
      model and ANOVA to examine variations in utilization of targeted therapies
      between geographic regions and used ARIMA models to estimate longitudinal trends.
      RESULTS: Population-adjusted use and costs of antineoplastic drugs (including
      targeted therapies) were highest in the southern region of Taiwan and lowest in
      the outer islands. We found a 4-fold difference in use of antineoplastic drugs
      and a 49-fold difference in use of targeted therapies between regions if the
      outer islands were included. There were minimal differences in use of
      antineoplastic drugs between other regions with about a 2-fold difference in use
      of targeted therapies. Without considering the outer islands, the market share by
      prescription volume and costs of targeted therapies increased almost 2-fold (1.84
      1.90) and 1.5-fold (1.26-1.61) respectively between 2009 and 2012. Furthermore,
      region was not significantly associated with use of antineoplastic agents or use
      of targeted therapies after adjusting for confounders. Region was associated with
      costs of antineoplastic agents but it was not associated with costs of targeted
      therapies after confounding adjustments. CONCLUSIONS: Use of antineoplastic drugs
      overall and use of targeted therapies for treatment of cancer varied somewhat
      between regions in Taiwan; use was notably low in the outer islands. Strategies
      might be needed to ensure access to cancer care in each region as economic burden
      of cancer care increase due to growing use of targeted therapies.

PMID- 28768505
TI  - Tough decoy targeting of predominant let-7 miRNA species in adult human
      hematopoietic cells.
AB  - BACKGROUND: In humans, the heterochronic cascade composed of the RNA-binding
      protein LIN28 and its major target, the let-7 family of microRNAs (miRNAs), is
      highly regulated during human erythroid ontogeny. Additionally, down-regulation
      of the let-7 miRNAs in cultured adult CD34(+) cells or the over-expression of
      LIN28 in cultured erythrocytes from pediatric patients with HbSS genotype causes
      increased levels of fetal hemoglobin (HbF) in the range of 19-40% of the total.
      Therefore, we hypothesized that focused targeting of individual let-7 miRNA
      family members would exhibit regulatory effect on HbF expression in human adult
      erythroblasts. METHODS: The expression levels of mature let-7 family members were
      measured by RT-qPCR in purified cell populations sorted from peripheral blood. To
      study the effects of let-7 miRNAs upon globin expression, a lentiviral construct
      that incorporated the tough decoy (TuD) design to target let-7a or let-7b was
      compared with empty vector controls. Transductions were performed in CD34(+)
      cells from adult healthy volunteers cultivated ex vivo in erythropoietin
      supplemented serum-free media for 21 days. Downstream analyses included RT-qPCR,
      Western blot and HPLC for the characterization of adult and fetal hemoglobins.
      RESULTS: The expression of individual let-7 miRNA family members in adult
      peripheral blood cell populations demonstrated that let-7a and let-7b miRNAs are
      expressed at much higher levels than the other let-7 family members in purified
      adult human blood cell subsets with expression being predominantly in
      reticulocytes. Therefore, we focused this study upon the targeted inhibition of
      let-7a and let-7b with the TuD design to explore its effects upon developmentally
      timed erythroid genes. Let-7a-TuD transductions significantly increased gamma
      globin mRNA expression and HbF to an average of 38%. Let-7a-TuD also
      significantly decreased the mRNA expression of some ontogeny-regulated erythroid
      genes, namely CA1 and GCNT2. In addition, the erythroid-related transcription
      factors BCL11A and HMGA2 were down- and up-regulated, respectively, by let-7a
      TuD, while ZBTB7A, KLF1 and SOX6 remained unchanged. CONCLUSIONS: Overall, our
      data demonstrate that let-7 miRNAs are differentially expressed in human
      hematopoietic cells, and that targeted inhibition of the highly-expressed species
      of this family is sufficient for developmentally-specific changes in gamma-globin
      expression and HbF levels.

PMID- 28768506
TI  - A qualitative exploration of cervical and breast cancer stigma in Karnataka,
      India.
AB  - BACKGROUND: Breast and cervical cancer are two of the most common cancers among
      women worldwide and were the two leading causes of cancer related death for women
      in India in 2013. While it is recognized that psychosocial and cultural factors
      influence access to education, prevention, screening and treatment, the role of
      stigma related to these two cancers has received limited attention. METHODS: Two
      qualitative exploratory studies. One focusing on cervical cancer, the other on
      breast cancer, were conducted in Karnataka, India using in-depth interviews and
      focus group discussions. In the breast cancer study, 59 in-depth interviews were
      conducted with patients, primary caregivers and healthcare providers. In the
      cervical cancer study, 147 respondents were interviewed including older and
      younger women, husbands, healthcare providers and community leaders. While stigma
      was not the focus of either study, themes relating to stigma emerged and are the
      focus of this analysis. RESULTS: Cancer stigma emerged as a general theme across
      both data sets. It appeared throughout the transcripts as descriptions of how
      women with breast or cervical cancer would be treated and talked about by
      husbands, family and the community (manifestations of stigma) and the reasons for
      this behavior. Stigma as a theme also arose through discussions around managing
      disclosure of a cancer diagnosis. Stigma was juxtaposed with a narrative of
      support for women with cancer. Three major themes emerged as driving the
      manifestations of cancer stigma: fear of casual transmission of cancer; personal
      responsibility for having caused cancer, and; belief in and fear of the
      inevitability of disability and death with a cancer diagnosis. Manifestations of
      cancer stigma were described in terms of experienced (enacted) stigma, including
      isolation or verbal stigma, and anticipated (fear of) stigma, should a cancer
      diagnosis be disclosed. CONCLUSIONS: The presence in these communities of cancer
      stigma and its many forms emerged across both the cervical and breast cancer data
      sets. Stigma was a feared outcome of a cancer diagnosis and described as a
      barrier to screening, early diagnosis and treatment seeking for women with
      symptoms. While further research on cancer stigma is needed, this exploration of
      some of the driving factors provides insight for future programmatic efforts to
      reduce cancer stigma and improve access to information, screening and treatment.

PMID- 28768508
TI  - Successive monitoring surveys of selected banned and restricted pesticide
      residues in vegetables from the northwest region of China from 2011 to 2013.
AB  - BACKGROUND: A wide range of pesticides is applied for crop protection in
      vegetable cultivation in China. Regulation of pesticide maximum residue limits
      (MRLs) in vegetables is established but not fully enforced. And pesticide
      residues in vegetables were not well monitored. This study conducted the
      monitoring surveys from 2011 to 2013 to investigate the pesticides in vegetables
      in the northwest region of China. METHODS: A multi-residue gas
      chromatography/mass spectrometry method (GC/MS) was used in determination of
      pesticides in vegetable samples. The chi2 test was used to compare the
      concentration of pesticide residues. RESULTS: A total of 32 pesticide residues
      were detected in 518 samples from 20 types of vegetables in this study. 7.7% of
      the detected pesticide residues exceeded the MRLs. The percentages of residues
      that exceeded the MRLs for leafy, melon and fruit, and root vegetables were
      11.2%, 5.1%, and 1.6%, respectively. There was no seasonal difference in the
      proportion of samples that exceeded the MRLs in different vegetables. A total of
      84.3% (27/32) pesticides were detected at concentrations that exceeded MRLs. And
      of the 27 pesticides that exceeded the MRLs, 11 (40.7%) were banned for use in
      agriculture. The most frequently detected pesticides were Malathion (9.4%),
      Dichlorvos (8.7%), and Dimethoate (8.1%). CONCLUSION: The observed high rate of
      pesticides detected and high incidence of pesticide detection exceeding their
      MRLs in the commonly consumed vegetables indicated that the Good Agricultural
      Practices (GAP) may not be well followed. The management of pesticide use and
      control should be improved. Well-developed training programs should be initiated
      to improve pesticide application knowledge for farmers.

PMID- 28768509
TI  - Assessment of potential risk factors for new onset disabling low back pain in
      Japanese workers: findings from the CUPID (cultural and psychosocial influences
      on disability) study.
AB  - BACKGROUND: Most studies of risk factors for new low back pain (LBP) have been
      conducted in Western populations, but because of cultural and environmental
      differences, the impact of causal factors may not be the same in other countries.
      We used longitudinal data from the Cultural and Psychosocial Influences on
      Disability (CUPID) study to assess risk factors for new onset of disabling LBP
      among Japanese workers. METHODS: Data came from a 1-year prospective follow-up of
      nurses, office workers, sales/marketing personnel, and transportation workers,
      initially aged 20-59 years, who were employed in or near Tokyo. A baseline
      questionnaire included items on past history of LBP, personal characteristics,
      ergonomic work demands, and work-related psychosocial factors. Further
      information about LBP was collected at follow-up. Analysis was restricted to
      participants who had been free from LBP during the 12 months before baseline.
      Logistic regression was used to assess baseline risk factors for new onset of
      disabling LBP (i.e. LBP that had interfered with work) during the 12 months of
      follow-up. RESULTS: Among 955 participants free from LBP during the 12 months
      before baseline, 58 (6.1%) reported a new episode of disabling LBP during the 12
      month follow-up period. After mutual adjustment in a multivariate logistic
      regression analysis, which included the four factors that showed associations
      individually (p < 0.1) in analyses adjusted only for gender and age, the highest
      odds ratio (OR) was for past history of LBP (2.8, 95% [confidence interval {CI}]:
      1.6-4.9), followed by working >=60 h per week (1.8, 95% CI: 1.0-3.5) and lifting
      weights >=25 kg by hand (1.6, 95% CI: 0.9-3.0). When past history of LBP was
      excluded from the model, ORs for the remaining risk factors were virtually
      unchanged. CONCLUSIONS: Our findings suggest that among Japanese workers, as
      elsewhere, past history of LBP is a major risk factor for the development of new
      episodes of disabling back pain. They give limited support to the association
      with occupational lifting that has been observed in earlier research, both in
      Japan and in Western countries. In addition, they suggest a possible role of long
      working hours, which merits further investigation.

PMID- 28768510
TI  - Educational needs in patients with spondyloarthritis in Sweden - a mixed-methods
      study.
AB  - BACKGROUND: There is a demand for a flexible and individually tailored patient
      education to meet patients' specific needs and priorities, but this area has
      seldom been studied in patients with spondyloarthritis (SpA), a family of
      inflammatory rheumatic diseases. The aim of the present study was to identify
      needs and priorities in patient education in patients with SpA. A second aim was
      to investigate patients' experiences and preferences of receiving patient
      education. METHODS: Data collection included a questionnaire survey with the
      Educational Needs Assessment Tool (ENAT) and interviews, using a mixed-methods
      design. Patients were identified through a specialist clinic register.
      Descriptive data are presented as mean with standard deviation, or frequencies.
      Chi-square test and independent-samples t-test were used for group comparisons. A
      manifest qualitative conventional content analysis was conducted to explore
      patients' experiences and needs in patient education, based on two focus groups
      (n = 6) and five individual interviews. RESULTS: Almost half (43%) of the 183 SpA
      patients had educational needs, particularly regarding aspects of self-help,
      feelings, and the disease process. More educational needs were reported by women
      and in patients with higher disease activity, while duration of disease did not
      affect the needs. The qualitative analysis highlighted the importance of
      obtaining a guiding, reliable, and easily available patient education for
      management of SpA. Individual contacts with healthcare professionals were of
      importance, but newer media were also requested. CONCLUSION: There are
      considerable educational needs in patients with SpA, and education concerning
      self-help, feelings, and the diseases process were raised as important issues.
      Healthcare professionals need to consider the importance of presenting varied
      formats of education based on the experiences and preferences of patients with
      SpA.

PMID- 28768511
TI  - German dentists' websites on periodontitis have low quality of information.
AB  - BACKGROUND: The internet is an increasingly relevant source of health
      information. We aimed to assess the quality of German dentists' websites on
      periodontitis, hypothesizing that it was significantly associated with a number
      of practice-specific parameters. METHODS: We searched four electronic search
      engines and included pages which were freely accessible, posted by a dental
      practice in Germany, and mentioned periodontal disease/therapy. Websites were
      assessed for (1) technical and functional aspects, (2) generic quality and risk
      of bias, (3) disease-specific information. For 1 and 2, validated tools
      (LIDA/DISCERN) were used for assessment. For 3, we developed a criterion
      catalogue encompassing items on etiologic and prognostic factors for
      periodontitis, the diagnostic and treatment process, and the generic chance of
      tooth retention in periodontitis patients. Inter- and intra-rater reliabilities
      were largely moderate. Generalized linear modeling was used to assess the
      association between the information quality (measured as % of maximally available
      scores) and practice-specific characteristics. RESULTS: Seventy-one websites were
      included. Technical and functional aspects were reported in significantly higher
      quality (median: 71%, 25/75th percentiles: 67/79%) than all other aspects (p <
      0.05). Generic risk of bias and most disease-specific aspects showed
      significantly lower reporting quality (median range was 0-40%), with poorest
      reporting for prognostic factors (9;0/27%), diagnostic process (0;0/33%) and
      chances of tooth retention (0;0/2%). We found none of the practice-specific
      parameters to have significant impact on the overall quality of the websites.
      CONCLUSIONS: Most German dentists' websites on periodontitis are not fully
      trustworthy and relevant information are not or insufficiently considered. There
      is great need to improve the information quality from such websites at least with
      regards to periodontitis.

PMID- 28768512
TI  - Theory of synergistic effects: Hill-type response surfaces as 'null-interaction'
      models for mixtures.
AB  - BACKGROUND: The classification of effects caused by mixtures of agents as
      synergistic, antagonistic or additive depends critically on the reference model
      of 'null interaction'. Two main approaches are currently in use, the Additive
      Dose (ADM) or concentration addition (CA) and the Multiplicative Survival (MSM)
      or independent action (IA) models. We compare several response surface models to
      a newly developed Hill response surface, obtained by solving a logistic partial
      differential equation (PDE). Assuming that a mixture of chemicals with individual
      Hill-type dose-response curves can be described by an n-dimensional logistic
      function, Hill's differential equation for pure agents is replaced by a PDE for
      mixtures whose solution provides Hill surfaces as 'null-interaction' models and
      relies neither on Bliss independence or Loewe additivity nor uses Chou's unified
      general theory. METHODS: An n-dimensional logistic PDE decribing the Hill-type
      response of n-component mixtures is solved. Appropriate boundary conditions
      ensure the correct asymptotic behaviour. Mathematica 11 (Wolfram, Mathematica
      Version 11.0, 2016) is used for the mathematics and graphics presented in this
      article. RESULTS: The Hill response surface ansatz can be applied to mixtures of
      compounds with arbitrary Hill parameters. Restrictions which are required when
      deriving analytical expressions for response surfaces from other principles, are
      unnecessary. Many approaches based on Loewe additivity turn out be special cases
      of the Hill approach whose increased flexibility permits a better description of
      'null-effect' responses. Missing sham-compliance of Bliss IA, known as Colby's
      model in agrochemistry, leads to incompatibility with the Hill surface ansatz.
      Examples of binary and ternary mixtures illustrate the differences between the
      approaches. For Hill-slopes close to one and doses below the half-maximum effect
      doses MSM (Colby, Bliss, Finney, Abbott) predicts synergistic effects where the
      Hill model indicates 'null-interaction'. These differences increase considerably
      with increasing steepness of the individual dose-response curves. CONCLUSION: The
      Hill response surface ansatz contains the Loewe additivity concept as a special
      case and is incompatible with Bliss independent action. Hence, when synergistic
      effects are claimed, those dose combinations deserve special attention where the
      differences between independent action approaches and Hill estimations are large.

PMID- 28768513
TI  - Clinical and laboratory predictors of death in African children with features of
      severe malaria: a systematic review and meta-analysis.
AB  - BACKGROUND: The criteria for defining severe malaria have evolved over the last
      20 years. We aimed to assess the strength of association of death with features
      currently characterizing severe malaria through a systematic review and meta
      analysis. METHOD: Electronic databases (Medline, Embase, Cochrane Database of
      Systematic Reviews, Thomson Reuters Web of Knowledge) were searched to identify
      publications including African children with severe malaria. PRISMA guidelines
      were followed. Selection was based on design (epidemiological, clinical and
      treatment studies), setting (Africa), participants (children < 15 years old with
      severe malaria), outcome (survival/death rate), and prognostic indicators
      (clinical and laboratory features). Quality assessment was performed following
      the criteria of the 2011 Quality Assessment of Diagnostic Accuracy Studies
      (QUADAS-2). Odds ratios (ORs) were calculated for each study and prognostic
      indicator, and, when a test was assessed in at least two studies, pooled
      estimates of ORs were computed using fixed- or random-effects meta-analysis.
      RESULTS: A total of 601 articles were identified and screened and 30 publications
      were retained. Features with the highest pooled ORs were renal failure (5.96, 95%
      CI 2.93-12.11), coma score (4.83, 95% CI 3.11-7.5), hypoglycemia (4.59, 95% CI
      2.68-7.89), shock (4.31, 95% CI 2.15-8.64), and deep breathing (3.8, 95% CI 3.29
      4.39). Only half of the criteria had an OR > 2. Features with the lowest pooled
      ORs were impaired consciousness (0.58, 95% CI 0.25-1.37), severe anemia (0.76,
      95% CI 0.5- 1.13), and prostration (1.12, 95% CI 0.45-2.82). CONCLUSION: The
      findings of this meta-analysis show that the strength of association between the
      criteria defining severe malaria and death is quite variable for each clinical
      and/or laboratory feature (OR ranging from 0.58 to 5.96). This ranking allowed
      the identification of features weakly associated with death, such as impaired
      consciousness and prostration, which could assist to improve case definition, and
      thus optimize antimalarial treatment.

PMID- 28768514
TI  - Sensitivity and specificity of a real-time reverse transcriptase polymerase chain
      reaction detecting feline coronavirus mutations in effusion and serum/plasma of
      cats to diagnose feline infectious peritonitis.
AB  - BACKGROUND: Feline coronavirus (FCoV) exists as two pathotypes, and FCoV spike
      gene mutations are considered responsible for the pathotypic switch in feline
      infectious peritonitis (FIP) pathogenesis. The aim of this study was to evaluate
      sensitivity and specificity of a real-time reverse transcriptase polymerase chain
      reaction (RT-PCR) specifically designed to detect FCoV spike gene mutations at
      two nucleotide positions. It was hypothesized that this test would correctly
      discriminate feline infectious peritonitis virus (FIPV) and feline enteric
      coronavirus (FECV). METHODS: The study included 63 cats with signs consistent
      with FIP. FIP was confirmed in 38 cats. Twenty-five control cats were
      definitively diagnosed with a disease other than FIP. Effusion and/or
      serum/plasma samples were examined by real-time RT-PCR targeting the two FCoV
      spike gene fusion peptide mutations M1058 L and S1060A using an allelic
      discrimination approach. Sensitivity, specificity, negative and positive
      predictive values including 95% confidence intervals (95% CI) were calculated.
      RESULTS: FIPV was detected in the effusion of 25/59 cats, one of them being a
      control cat with chronic kidney disease. A mixed population of FIPV/FECV was
      detected in the effusion of 2/59 cats; all of them had FIP. RT-PCR was negative
      or the pathotype could not be determined in 34/59 effusion samples. In effusion,
      sensitivity was 68.6% (95% CI 50.7-83.2), specificity was 95.8% (95% CI 78.9
      99.9). No serum/plasma samples were positive for FIPV. CONCLUSIONS: Although
      specificity of the test in effusions was high, one false positive result
      occurred. The use of serum/plasma cannot be recommended due to a low viral load
      in blood.

PMID- 28768515
TI  - A comparative assessment of antiproliferative properties of resveratrol and
      ethanol leaf extract of Anogeissus leiocarpus (DC) Guill and Perr against HepG2
      hepatocarcinoma cells.
AB  - BACKGROUND: Epidemiological and experimental evidences have shown cancer as a
      leading cause of death worldwide. Although the folklore use of plants as a
      reliable source of health-restoring principles is well-documented, the search for
      more of such plants that are active against diseases, such as cancer, continues.
      We report here a laboratory-based evidence of the relevance of an ethanol leaf
      extract of Anogeissus leiocarpus (A2L) in comparison with resveratrol, a natural
      polyphenol, in cancer therapy. METHODS: The quantitative assessment of flavonoid
      and phenolic contents involved quercetin and gallic acid as standards,
      respectively were determined using spectrophotometry. Cytotoxicity was determined
      fluorometrically using propidium-iodide-staining method. Antioxidant status,
      adenosine triphosphate (ATP) levels, caspase activities and mitochondrial
      integrity were assessed using fluorometry/luminometry. RESULTS: The antioxidant
      assay demonstrated that A2L possesses a strong antioxidant capacity as compared
      with the reference compounds, ascorbic acid and butylated hydroxytoluene. This is
      further buttressed by the significantly high level of phenolics obtained in the
      quantitative assessment of the extract. A 72-h post-treatment examination
      indicated that both A2L and resveratrol modulate the proliferation of HepG2 liver
      carcinoma cells in a time- and concentration-dependent manner. Determination of
      the total nuclei area, propidium-iodide negative and positive nuclei areas all
      further buttress the modulation of cell proliferation by A2L and resveratrol with
      the indication that the observed cell death is due to apoptosis and necrosis at
      lower and higher concentrations of treatments respectively. At lower
      concentrations (0.39-3.13 MUg/mL), resveratrol possesses higher tendencies to
      activate caspases 3 and 7. Bioenergetically, both resveratrol and A2L do not
      adversely affect the cells at lower concentrations (0.39-6.25 MUg/mL for
      resveratrol and 12.5-100.0 MUg/mL for A2L) except at higher concentrations (12.5
      25.0 MUg/mL for resveratrol and 200-800 MUg/mL for A2L) which are more pronounced
      in A2L-treated cells. Furthermore, the antioxidant status of HepG2 cells is not
      perturbed by resveratrol as compared with A2L. Assessment of 24-h post-treatment
      mitochondrial function shows that resveratrol is not mitotoxic as compared with
      A2L which exhibits mitotoxicity at its highest concentration. CONCLUSIONS: Taken
      together, findings from this study showed that A2L possesses strong
      antiproliferative activity and its prospect in the management of hepatocellular
      carcinoma deserves further investigation.

PMID- 28768516
TI  - Anti-Mullerian hormone is linked to the type of early pregnancy loss in
      idiopathic recurrent miscarriage: a retrospective cohort study.
AB  - We correlated Anti-Mullerian hormone (AMH) levels and other parameters for
      ovarian reserve to the gestational age at the time of pregnancy loss in women
      with idiopathic recurrent miscarriage. In a retrospective study, 79 patients had
      suffered a total of 266 miscarriages. When comparing women with an "unembryonic"
      to those with an "embryonic" most recent miscarriage, there was no difference in
      median age (36.3 years, IQR 31.6-40.1 versus 34.2 years, IQR 29.9-38.0; p =
      0.303) but in median AMH levels (0.7, IQR 0.2-18, versus median 1.8, IQR 1.3-3.3,
      respectively, p = 0.044) and in the rate of patients with an AMH <= 1 ng/mL
      (23/37, 62.2%, versus 8/42, 19%; p < 0.001). Thus, AMH might add to the
      diagnostic process in recurrent miscarriage in the future.

PMID- 28768517
TI  - Automated assessments of circumferential strain from cine CMR correlate with LVEF
      declines in cancer patients early after receipt of cardio-toxic chemotherapy.
AB  - BACKGROUND: In patients with cancer receiving potentially cardio-toxic
      chemotherapy, measurements of left ventricular (LV) circumferential or
      longitudinal strain are often used clinically to identify myocardial dysfunction.
      Using a new software algorithm, we sought to determine in individuals receiving
      treatment for cancer the association between automated assessments of LV mean mid
      wall circumferential strain and conventional measures of LV ejection fraction
      (EF) both obtained from cardiovascular magnetic resonance (CMR) cine balanced
      steady-state free-precession (bSSFP) white-blood acquisitions. METHODS: Before
      and 3 months after initiating treatment with potentially cardio-toxic
      chemotherapy, 72 individuals (aged 54 +/- 14 years with breast cancer [39%],
      lymphoma [49%], or sarcoma [12%]) underwent serial CMR cine bSSFP assessments of
      LV volumes and EF, and mean mid-wall circumferential strain determined from these
      same cine images as well as from additional tagged CMR images. On the cine
      images, assessments of strain were obtained using the newly developed deformation
      based segmentation algorithm. Assessments of LV volumes/EF from the cine images
      and strain from tagged CMR were accomplished using commercially available
      software. All measures were analyzed in a blinded fashion independent of one
      another. RESULTS: Acceptable measures for the automated assessments of mean mid
      wall circumferential strain from the cine images were obtained in 142 of 144
      visits (98.6%) with an overall analysis time averaging 6:47 +/- 1:06 min. The
      results from these automated measures averaged -18.8 +/- 2.9 at baseline and 
      17.6 +/- 3.1 at 3 months (p = 0.001). Left ventricular EF declined slightly from
      65 +/- 7% at baseline to 62 +/- 7% at 3 months (p = 0.0002). The correlation
      between strain from cine imaging and LVEF was r = -0.61 (p < 0.0001). In
      addition, the 3-month changes in LV strain and LVEF were correlated (r = -0.49; p
      < 0.0001). The correlation between cine and tagged derived assessments of strain
      was r = 0.23; p = 0.01. CONCLUSIONS: Automated measures of LV mean mid-wall
      circumferential strain can be obtained in 63/4 minutes from cine bSSFP LV short
      axis images (used concurrently to assess LV volumes and EF) in 98.6% of patients
      receiving treatment for cancer with potentially cardio-toxic chemotherapy. These
      cine derived measures of circumferential strain correlate with early subclinical
      declines in LVEF.

PMID- 28768518
TI  - Water, sanitation and hygiene infrastructure and quality in rural healthcare
      facilities in Rwanda.
AB  - BACKGROUND: WHO and UNICEF have proposed an action plan to achieve universal
      water, sanitation and hygiene (WASH) coverage in healthcare facilities (HCFs) by
      2030. The WASH targets and indicators for HCFs include: an improved water source
      on the premises accessible to all users, basic sanitation facilities, a hand
      washing facility with soap and water at all sanitation facilities and patient
      care areas. To establish viable targets for WASH in HCFs, investigation beyond
      'access' is needed to address the state of WASH infrastructure and service
      provision. Patient and caregiver use of WASH services is largely unaddressed in
      previous studies despite being critical for infection control. METHODS: The state
      of WASH services used by staff, patients and caregivers was assessed in 17 rural
      HCFs in Rwanda. Site selection was non-random and predicated upon piped water and
      power supply. Direct observation and semi-structured interviews assessed drinking
      water treatment, presence and condition of sanitation facilities, provision of
      soap and water, and WASH-related maintenance and record keeping. Samples were
      collected from water sources and treated drinking water containers and analyzed
      for total coliforms, E. coli, and chlorine residual. RESULTS: Drinking water
      treatment was reported at 15 of 17 sites. Three of 18 drinking water samples
      collected met the WHO guideline for free chlorine residual of >0.2 mg/l, 6 of 16
      drinking water samples analyzed for total coliforms met the WHO guideline of <1
      coliform/100 mL and 15 of 16 drinking water samples analyzed for E. coli met the
      WHO guideline of <1 E. coli/100 mL. HCF staff reported treating up to 20 L of
      drinking water per day. At all sites, 60% of water access points (160 of 267)
      were observed to be functional, 32% of hand washing locations (46 of 142) had
      water and soap and 44% of sanitary facilities (48 of 109) were in hygienic
      condition and accessible to patients. Regular maintenance of WASH infrastructure
      consisted of cleaning; no HCF had on-site capacity for performing repairs.
      Quarterly evaluations of HCFs for Rwanda's Performance Based Financing system
      included WASH indicators. CONCLUSIONS: All HCFs met national policies for water
      access, but WHO guidelines for environmental standards including water quality
      were not fully satisfied. Access to WASH services at the HCFs differed between
      staff and patients and caregivers.

PMID- 28768519
TI  - Synthetic hematocrit derived from the longitudinal relaxation of blood can lead
      to clinically significant errors in measurement of extracellular volume fraction
      in pediatric and young adult patients.
AB  - BACKGROUND: Extracellular volume fraction (ECV) is altered in pathological
      cardiac remodeling and predicts death and arrhythmia. ECV can be quantified using
      cardiovascular magnetic resonance (CMR) T1 mapping but calculation requires a
      measured hematocrit (Hct). The longitudinal relaxation of blood has been used in
      adults to generate a synthetic Hct (estimate of true Hct) but has not been
      validated in pediatric populations. METHODS: One hundred fourteen children and
      young adults underwent a total of 163 CMRs with T1 mapping. The majority of
      subjects had a measured Hct the same day (N = 146). Native and post-contrast T1
      were determined in blood pool, septum, and free wall of mid-LV, avoiding areas of
      late gadolinium enhancement. Synthetic Hct and ECV were calculated and intraclass
      correlation coefficient (ICC) and linear regression were used to compare measured
      and synthetic values. RESULTS: The mean age was 16.4 +/- 6.4 years and mean left
      ventricular ejection fraction was 59% +/- 9%. The mean measured Hct was 41.8 +/-
      3.0% compared to the mean synthetic Hct of 43.2% +/- 2.9% (p < 0.001, ICC 0.46
      [0.27, 0.52]) with the previously published model and 41.8% +/- 1.4% (p < 0.001,
      ICC 0.28 [0.13, 0. 42]) with the locally-derived model. Mean measured mid-free
      wall ECV was 30.5% +/- 4.8% and mean synthetic mid-free wall ECV of local model
      was 29.7% +/- 4.6% (p < 0.001, ICC 0.93 [0.91, 0.95]). Correlations were not
      affected by heart rate and did not significantly differ in subpopulation
      analysis. While the ICC was strong, differences between measured and synthetic
      ECV ranged from -8.4% to 4.3% in the septum and -12.6% to 15.8% in the free wall.
      Using our laboratory's normal cut-off of 28.5%, 59 patients (37%) were
      miscategorized (53 false negatives, 6 false positives) with published model ECV.
      The local model had 37 miscategorizations (20 false negatives, 17 false
      positives), significantly fewer but still a substantial number (23%).
      CONCLUSIONS: Our data suggest that use of synthetic Hct for the calculation of
      ECV results in miscategorization of individual patients. This difference may be
      less significant once synthetic ECV is calculated and averaged over a large
      research cohort, making it potentially useful as a research tool. However, we
      recommend formal measurement of Hct in children and young adults for clinical
      CMRs.

PMID- 28768521
TI  - Searching for cancer vulnerabilities amid genetic chaos.
AB  - A meeting report on the Third European Association for Cancer Research Conference
      on Cancer Genomics, held at Churchill College, Cambridge, UK, 25-28 June 2017.

PMID- 28768520
TI  - Colorectal cancer in a patient with intestinal schistosomiasis: a case report
      from Kilimanjaro Christian Medical Center Northern Zone Tanzania.
AB  - BACKGROUND: Colorectal cancer associated with chronic intestinal schistosomiasis
      has been linked with the chronic inflammation as a result of schistosomal ova
      deposition in the submucosal layer of the intestine. Among all species
      Schistosoma japonicum has been more linked to development of colorectal cancer as
      compared to Schistosoma mansoni due to absence of population-based studies to
      support the association. Despite the weak evidence, some cases have been reported
      associating S. mansoni with development of colorectal cancer. CASE PRESENTATION:
      We report a patient who presented to us as a case of intestinal obstruction and
      found to have a constrictive lesion at the sigmoid colon at laparotomy, then
      later found to have colorectal cancer with deposited S. mansoni ova at histology.
      CONCLUSION: Given the known late complications of schistosomiasis, and as S.
      mansoni is endemic in some parts of Tanzania, epidemiological studies are
      recommended to shed more light on its association with colorectal cancer.

PMID- 28768522
TI  - Exploring the reliability and acceptability of cognitive tests for Indigenous
      Australians: a pilot study.
AB  - BACKGROUND: Reliable cognitive assessment for Indigenous Australians is difficult
      given that mainstream tests typically rely on Western concepts, content and
      values. A test's psychometric properties should therefore be assessed prior to
      use in other cultures. The aim of this pilot study was to examine the reliability
      and acceptability of four cognitive tests for Australian Aboriginal people.
      METHODS: Participants were 40 male and 44 female (N = 84) Aboriginal patients
      from Alice Springs Hospital. Four tests were assessed for reliability and
      acceptability - Rowland Universal Dementia Assessment Screen (RUDAS) (n = 19),
      PEBL Corsi Blocks (Corsi) (n = 19), Story Memory Recall Test (SMRT) (n = 17) and
      a CogState battery (n = 18). Participants performed one to three of the tests
      with repeated assessment to determine test-retest reliability. Qualitative
      interviews were conducted and analysed based on an adapted phenomenological
      approach to explore test acceptability. An Indigenous Reference Group gave advice
      and guidance. RESULTS: Intra-class correlations (ICC) for test retest reliability
      ranged from r = 0.58 (CogState One Back accuracy) to 0.86 (RUDAS). Themes emerged
      relating to general impressions, impacts on understanding and performance,
      appropriateness, task preferences and suggested improvements. CONCLUSIONS: RUDAS,
      CogState Identification task, and SMRT showed the highest reliabilities. Overall
      the tests were viewed as a positive challenge and an opportunity to learn about
      the brain despite provoking some anxiety in the patients. Caveats for test
      acceptability included issues related to language, impacts of convalescence and
      cultural relevance.

PMID- 28768523
TI  - Genetic signature analysis of Perkinsus marinus in Mexico suggests possible
      translocation from the Atlantic Ocean to the Pacific coast of Mexico.
AB  - BACKGROUND: The protozoan Perkinsus marinus (Mackin, Owen & Collier) Levine, 1978
      causes perkinsosis in the American oyster Crassostrea virginica Gmelin, 1791.
      This pathogen is present in cultured C. virginica from the Gulf of Mexico and has
      been reported recently in Saccostrea palmula (Carpenter, 1857), Crassostrea
      corteziensis (Hertlein, 1951) and Crassostrea gigas (Thunberg, 1793) from the
      Mexican Pacific coast. Transportation of fresh oysters for human consumption and
      repopulation could be implicated in the transmission and dissemination of this
      parasite across the Mexican Pacific coast. The aim of this study was two-fold.
      First, we evaluated the P. marinus infection parameters by PCR and RFTM (Ray's
      fluid thioglycollate medium) in C. virginica from four major lagoons (Terminos
      Lagoon, Campeche; Carmen-Pajonal-Machona Lagoon complex, Tabasco; Mandinga
      Lagoon, Veracruz; and La Pesca Lagoon, Tamaulipas) from the Gulf of Mexico.
      Secondly, we used DNA sequence analyses of the ribosomal non-transcribed spacer
      (rNTS) region of P. marinus to determine the possible translocation of this
      species from the Gulf of Mexico to the Mexican Pacific coast. RESULTS: Perkinsus
      marinus prevalence by PCR was 57.7% (338 out of 586 oysters) and 38.2% (224 out
      of 586 oysters) by RFTM. The highest prevalence was observed in the Carmen
      Pajonal-Machona Lagoon complex in the state of Tabasco (73% by PCR and 58% by
      RFTM) and the estimated weighted prevalence (WP) was less than 1.0 in the four
      lagoons. Ten unique rDNA-NTS sequences of P. marinus [termed herein the "P.
      marinus (Pm) haplotype"] were identified in the Gulf of Mexico sample. They
      shared 96-100% similarity with 18 rDNA-NTS sequences from the GenBank database
      which were derived from 16 Mexican Pacific coast infections and two sequences
      from the USA. The phylogenetic tree and the haplotype network showed that the P.
      marinus rDNA-NTS sequences from Mexico were distant from the rDNA-NTS sequences
      of P. marinus reported from the USA. The ten rDNA-NTS sequences described herein
      were restricted to specific locations displaying different geographical
      connections within the Gulf of Mexico; the Carmen-Pajonal-Machona Pm1 haplotype
      from the state of Tabasco shared a cluster with P. marinus isolates reported from
      the Mexican Pacific coast. CONCLUSIONS: The rDNA-NTS sequences of P. marinus from
      the state of Tabasco shared high similarity with the reference rDNA-NTS sequences
      from the Mexican Pacific coast. The high similarity suggests a transfer of
      oysters infected with P. marinus from the Mexican part of the Gulf of Mexico into
      the Mexican Pacific coast.

PMID- 28768524
TI  - Dexmedetomidine as a promising prevention strategy for cardiac surgery-associated
      acute kidney injury: a meta-analysis.

PMID- 28768525
TI  - Protocol: systematic review of the association between socio-economic status and
      survival in adult head and neck cancer.
AB  - BACKGROUND: Head and neck cancer incidence is increasing worldwide. Despite
      overall improvements in survival, numerous studies suggest worse survival in more
      disadvantaged populations; however, this literature has not been systematically
      reviewed. The aim of this review is to investigate whether lower compared to
      higher socioeconomic status (SES) influences survival in head and neck squamous
      cell cancer (HNSCC) and explore possible explanations for any relationship found.
      METHOD: A systematic strategy will be used to identify articles, appraise their
      quality and extract data. Online databases including MEDLINE, Web of Knowledge,
      ESBCO Host and Scopus will be used to locate observational studies of adults with
      a primary diagnosis of head and neck cancer in EU15+ countries (15 members of the
      EU, Australia, Canada, Norway, USA and New Zealand) where the outcomes report
      associations between SES and survival. This will be augmented by searching for
      grey literature and through reference lists. Data will be extracted using a
      standardised form. Study quality will be assessed using the Newcastle Ottawa
      scale and where possible meta-analysis of the pooled data will be conducted.
      DISCUSSION: This review will quantify the association between SES and survival
      outcomes for adult head and neck cancer patients in developed countries. The
      results will help identify gaps in the literature and therefore direct further
      novel research in the field. Ultimately, this will inform public policy and
      strategies to reduce the inequalities in HNSCC survival. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42016037019 .

PMID- 28768526
TI  - Early occurrence of childhood dental caries among low literate families.
AB  - OBJECTIVE: The purpose of this cross-sectional study was to identify the oral
      health status and influencing factors in preschool children in Tabriz, Iran. A
      total of 756 children from 20% of the total district preschools were selected
      using a two-step random sampling procedure. Questionnaires were used to collect
      demographic and socio-economic data. Oral exams were conducted by a single
      pediatric dentist to assess the children's oral health, and to determine the
      number of decayed, missing, and filled teeth (dmft) according to the World Health
      Organization's (WHO) definition of caries. RESULTS: Out of 756 preschool
      children, 51.5% boys with mean age of years 5.76 (SD = 0.78) were enrolled. The
      median (25th-75th Pertcentile) of dmft index in boys and girls was 4 (2-9) and 5
      (2-8), respectively. Only 15.1% children had decay-free teeth. The results of
      univariate analysis showed a significant relationship between dmft index and
      child age (P < 0.001), mother's years of education (P = 0.001), mother's
      employment status (P < 0.001), and family socio-economic status (P < 0.001). On
      multivariate analysis, statistical significance was found in sex (P = 0.007), age
      groups except for 5 years (P = 0.210), mother's education status (P < 0.001) as
      well as in families with intermediate (P = 0.024), and high (P = 0.072) socio
      economic status.

PMID- 28768527
TI  - Bilateral blindness secondary to optic nerve ischemia from severe amlodipine
      overdose: a case report.
AB  - BACKGROUND: Calcium channel blockers are commonly prescribed medications; calcium
      channel blocker overdose is becoming increasingly prevalent. The typical
      presentation of a calcium channel blocker overdose is hypotension and decreased
      level of consciousness. We describe a case of a calcium channel blocker overdose
      that led to bilateral cortical blindness, a presentation that has not previously
      been reported. CASE PRESENTATION: A 49-year-old white woman with known bilateral
      early optic atrophy presented to our hospital with hypotension and obtundation
      following a known ingestion of 150 mg of amlodipine. She was transferred to our
      intensive care unit where she was intubated, mechanically ventilated, and
      required maximal vasopressor support (norepinephrine 40 mcg/minute, epinephrine
      40 mcg/minute, and vasopressin 2.4 units/hour) along with intravenously
      administered crystalloid boluses. Despite these measures, she continued to
      deteriorate with persistent hypotension and tachycardia, as well as anuria.
      Intralipid emulsion therapy was subsequently administered to which no initial
      response was observed. A chest X-ray revealed diffuse pulmonary edema;
      intravenous diuresis as well as continuous renal replacement therapy was
      initiated. Following the initiation of continuous renal replacement therapy, her
      oxygen requirements as well as urine output began to improve, and 3 days later
      she was liberated from mechanical ventilation. Following extubation, she
      complained of new onset visual impairment, specifically seeing only red-green
      colors, but no objects. An ophthalmologic examination revealed that this was due
      to bilateral optic atrophy from prolonged hypotension during the first 24 hours
      after the overdose. CONCLUSION: Persistent hypotension in the setting of a
      calcium channel blocker overdose can lead to worsening optic atrophy resulting in
      bilateral cortical blindness.

PMID- 28768528
TI  - Safety, tolerability, clinical, and joint structural outcomes of a single intra
      articular injection of allogeneic mesenchymal precursor cells in patients
      following anterior cruciate ligament reconstruction: a controlled double-blind
      randomised trial.
AB  - BACKGROUND: Few clinical trials have investigated the safety and efficacy of
      mesenchymal stem cells for the management of post-traumatic osteoarthritis. The
      objectives of this pilot study were to determine the safety and tolerability and
      to explore the efficacy of a single intra-articular injection of allogeneic human
      mesenchymal precursor cells (MPCs) to improve clinical symptoms and retard joint
      structural deterioration over 24 months in patients following anterior cruciate
      ligament (ACL) reconstruction. METHODS: In this phase Ib/IIa, double-blind,
      active comparator clinical study, 17 patients aged 18-40 years with unilateral
      ACL reconstruction were randomized (2:1) to receive either a single intra
      articular injection of 75 million allogeneic MPCs suspended in hyaluronan (HA)
      (MPC + HA group) (n = 11) or HA alone (n = 6). Patients were monitored for
      adverse events. Immunogenicity was evaluated by anti-HLA panel reactive
      antibodies (PRA) against class I and II HLAs determined by flow cytometry. Pain,
      function, and quality of life were assessed using the Knee Injury and
      Osteoarthritis Outcome Score (KOOS) and SF-36v2 scores. Joint space width was
      measured from radiographs, and tibial cartilage volume and bone area assessed
      from magnetic resonance imaging (MRI). RESULTS: Moderate arthralgia and swelling
      within 24 h following injection that subsided were observed in 4 out of 11 in the
      MPC + HA group and 0 out of 6 HA controls. No cell-related serious adverse
      effects were observed. Increases in class I PRA >10% were observed at week 4 in
      the MPC + HA group that decreased to baseline levels by week 104. Compared with
      the HA group, MPC + HA-treated patients showed greater improvements in KOOS pain,
      symptom, activities of daily living, and SF-36 bodily pain scores (p < 0.05). The
      MPC + HA group had reduced medial and lateral tibiofemoral joint space narrowing
      (p < 0.05), less tibial bone expansion (0.5% vs 4.0% over 26 weeks, p = 0.02),
      and a trend towards reduced tibial cartilage volume loss (0.7% vs -4.0% over 26
      weeks, p = 0.10) than the HA controls. CONCLUSIONS: Intra-articular
      administration of a single allogeneic MPC injection following ACL reconstruction
      was safe, well tolerated, and may improve symptoms and structural outcomes. These
      findings suggest that MPCs warrant further investigations as they may modulate
      some of the pathological processes responsible for the development of post
      traumatic osteoarthritis following ACL reconstruction. TRIAL REGISTRATION:
      ClinicalTrials.gov ( NCT01088191 ) registration date: March 11, 2010 .

PMID- 28768529
TI  - Hyperglycaemia in critically ill patients: the immune system's sweet tooth.
AB  - There is an ongoing debate regarding the efficacy of glycaemic control in
      critically ill patients. Here we briefly highlight the key function of elevated
      glucose in critically ill patients, namely, to enable elevation of aerobic
      glycolysis in rapidly dividing cells. In particular, aerobic glycolysis provides
      metabolic intermediates necessary for expansion of biomass in immune cells and
      promotion of tissue repair. Furthermore, we emphasise that insulin may inhibit
      autophagy, a cell survival process used in the bulk degradation of cellular
      debris and damaged organelles. These observations provide a rational basis for
      tolerating elevated glucose levels in certain critically ill patients.

PMID- 28768530
TI  - Complications and health-related quality of life after robot-assisted versus open
      radical cystectomy: a systematic review and meta-analysis of four RCTs.
AB  - BACKGROUND: Radical cystectomy is associated with high rates of perioperative
      morbidity. Robotic-assisted radical cystectomy (RARC) is widely used today
      despite limited evidence for clinical superiority. The aim of this review was to
      evaluate the effect of RARC compared to open radical cystectomy (ORC) on
      complications and secondary on length of stay, time back to work and health
      related quality of life (HRQoL). METHODS: The databases PubMed, The Cochrane
      Library, Embase and CINAHL were searched. A systematic review according to the
      PRISMA guidelines and cumulative analysis was conducted. Randomized controlled
      trials (RCTs) that examined RARC compared to ORC were included in this review. We
      assessed the quality of evidence using the Cochrane Collaboration's 'Risk of
      bias' tool and Grading of Recommendations Assessment, Development and Evaluation
      approach. Data were extracted and analysed. RESULTS: The search retrieved 273
      articles. Four RCTs were included involving overall 239 patients. The quality of
      the evidence was of low to moderate quality. There was no significant difference
      between RARC and ORC in the number of patients developing complications within 30
      or 90 days postoperatively or in overall grade 3-5 complications within 30 or 90
      days postoperatively. Types of complications differed between the RARC and the
      ORC group. Likewise, length of stay and HRQoL at 3 and 6 months did not differ.
      CONCLUSION: Our review presents evidence for RARC not being superior to ORC
      regarding complications, LOS and HRQoL. High-quality studies with consistent
      registration of complications and patient-related outcomes are warranted.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016038232.

PMID- 28768531
TI  - The effect of glycopyrronium and indacaterol, as monotherapy and in combination,
      on the methacholine dose-response curve of mild asthmatics: a randomized three
      way crossover study.
AB  - BACKGROUND: Methacholine dose-response curves illustrate pharmacologic
      bronchoprotection against methacholine-induced airway hyperresponsiveness and can
      be used to quantitate changes in airway sensitivity (position), reactivity
      (slope), and maximal responsiveness following drug administration. Our objective
      was to determine the influence of single-dose glycopyrronium (long-acting
      muscarinic antagonist) and indacaterol (ultra-long acting beta2 agonist), as
      monotherapy and in combination, on the methacholine dose-response curve of mild
      asthmatics and to compare these findings with a non-asthmatic control curve.
      METHODS: This was a randomized, double blind, double dummy, three-way crossover
      study. For asthmatic participants (n = 14), each treatment arm included a
      baseline methacholine challenge, drug administration, and repeat methacholine
      challenges at 1, 24, and 48 h. Non-asthmatic control participants (n = 15)
      underwent a single methacholine challenge and did not receive any study
      treatment. Methacholine dose-response curves were graphed as the percent fall in
      forced expiratory volume in 1 s (FEV1) for each methacholine concentration
      administered. Best-fit curves were then generated. Differences in airway
      reactivity were calculated through linear regression. Changes in airway
      sensitivity were assessed as the shift in the provocative concentration of
      methacholine causing a 20% fall in FEV1. RESULTS: Compared to baseline, all
      treatments significantly reduced airway sensitivity to methacholine at 1 h post
      dose (indacaterol ~1.5 doubling concentrations; glycopyrronium ~5 doubling
      concentrations; combination ~5 doubling concentrations). Bronchoprotection at 24
      and 48 h remained significant with glycopyrronium and combination therapy only.
      Airway reactivity was not influenced by indacaterol whereas glycopyrronium
      significantly reduced airway reactivity at all time-points (p = 0.003-0.027). The
      combination significantly decreased slope at 1 (p = 0.021) and 24 (p = 0.039)
      hours only. The non-asthmatic control and 1-h glycopyrronium curves are nearly
      identical. Only the non-asthmatic control and 1-h post-combination therapy curves
      appeared to generate a true response plateau (three data points within 5%), which
      occurred at a 14% fall in FEV1. CONCLUSIONS: Methacholine dose-response curves
      differentiate the bronchoprotective mechanisms triggered by different classes of
      asthma medications. Assessment of bronchoprotection using methacholine dose
      response curves may be useful during clinical development of respiratory
      medications when performing superiority, equivalence, or non-inferiority trials.
      TRIAL REGISTRATION: clinicaltrials.gov ( NCT02953041 ). Retrospectively
      registered on October 24th 2016.

PMID- 28768532
TI  - Estrogen-like and tissue-selective effects of 7-methoxycoumarin from Ficus
      umbellata (Moraceae): an in vitro and in vivo study.
AB  - BACKGROUND: Ficus umbellata is a medicinal plant previously shown to endow
      estrogenic properties. Its major component was isolated and characterized as 7
      methoxycoumarin (MC). Noteworthy, coumarins and the respective active metabolite
      7-hydroxycoumarin analogs have shown aromatase inhibitory activity, which is of
      particular interest in the treatment of estrogen-dependent cancers. The present
      work aimed at evaluating the estrogenic/antiestrogenic effects of MC in vitro and
      in vivo. METHODS: To do so, in vitro assays using E-screen and reporter gene were
      done. In vivo, a 3-day uterotrophic assay followed by a postmenopausal-like rat
      model to characterize MC as well as F. umbellata aqueous extract in
      ovariectomized Wistar rats was performed. The investigations focused on
      histological (vaginal and uterine epithelial height) and morphological (uterine
      wet weight, vagina stratification and cornification) endpoints, bone mass,
      biochemical parameters and lipid profile. RESULTS: MC induced a significant (p <
      0.05) MCF-7 cell proliferation at a concentration of 0.1 MUM, but did not inhibit
      the effect induced by estradiol in both E-screen and reporter gene assays. In
      vivo, MC treatment did not show an uterotrophic effect in both rat models used.
      However, MC (1 mg/kg) induced a significant increase (p < 0.01) of vaginal
      epithelial height. No significant change was observed with MC in abdominal fat
      weight, serum lipid levels and bone weight. CONCLUSION: These results suggest
      that MC has a weak estrogenic activity in vitro and in vivo that accounts only in
      part to the estrogenicity of the whole plant extract. MC could be beneficial with
      regard to vagina dryness as it showed a tissue specific effect without exposing
      the uterus to a potential tumorigenic growth.

PMID- 28768534
TI  - The use of traditional medicine in maternity care among African women in Africa
      and the diaspora: a systematic review.
AB  - BACKGROUND: There is a paucity of literature describing traditional health
      practices and beliefs of African women. The purpose of this study was to
      undertake a systematic review of the use of traditional medicine (TM) to address
      maternal and reproductive health complaints and wellbeing by African women in
      Africa and the diaspora. METHOD: A literature search of published articles, grey
      literature and unpublished studies was conducted using eight medical and social
      science databases (CINAHL, EMBASE, Infomit, Ovid Medline, ProQuest, PsychINFO,
      PubMed and SCOPUS) from the inception of each database until 31 December 2016.
      Critical appraisal was conducted using a quality assessment tool (QAT). RESULT: A
      total of 20 studies conducted in 12 African countries representing 11,858 women
      were included. No literature was found on African women in the diaspora related
      to maternal use of TM or complementary and alternative medicine (CAM). The
      prevalence of TM use among the African women was as high as 80%. The most common
      TM used was herbal medicine for reasons related to treatment of pregnancy related
      symptoms. Frequent TM users were pregnant women with no formal education, low
      income, and living far from public health facilities. Lack of access to the
      mainstream maternity care was the major determining factor for use of TM.
      CONCLUSION: TM is widely used by African women for maternal and reproductive
      health issues due to lack of access to the mainstream maternity care. Further
      research is required to examine the various types of traditional and cultural
      health practices (other than herbal medicine), the beliefs towards TM, and the
      health seeking behaviors of African women in Africa and the diaspora.

PMID- 28768535
TI  - Developing a comprehensive response for treatment of children under 6 years of
      age with schistosomiasis: research and development of a pediatric formulation of
      praziquantel.
AB  - Schistosomiasis is a parasitic disease caused by blood flukes. The disease is
      caused by an inflammatory reaction to parasite eggs retained in the liver,
      bladder and reproductive organs. According to 2017 World Health Organization
      (WHO) estimates 220 million people are potentially infected, from which probably
      10% are children under 6 years of age. The regular treatment approach of a
      single, oral dose of 40 mg/kg body weight with praziquantel however, is difficult
      for children under the age of 6, leaving them without a treatment option. In
      order to address this important gap in treatment target populations, an
      international public-private partnership that works on a not-for-profit basis in
      the field of drug research and development for schistosomiasis was established in
      2012. This is called the Pediatric Praziquantel Consortium. Its mission was and
      continues to be to develop, register and provide access to a suitable pediatric
      praziquantel formulation for treating schistosomiasis in preschool-age children
      (3-6 months up to 6 years). The Target Product Profile for the pediatric
      formulation of praziquantel that would be suitable to treat children as young as
      3-6 months was then defined by a group of experts, including members from the
      Pediatric Praziquantel Consortium partner organizations as well as experts from
      WHO (as observer) and schistosomiasis endemic countries. The development of the
      drug is ongoing and the Pediatric Praziquantel Consortium aims to submit the
      regulatory dossier for marketing approval in endemic countries and WHO
      prequalification in 2018/19 with approval and product launch for schistosomiasis
      pediatric case management in key endemic countries in 2019. Ultimately, the goal
      is for the product to be considered for a large-scale mass distribution program
      by 2022.

PMID- 28768537
TI  - Erratum to: Severely deranged vital signs as triggers for acute treatment
      modifications on an intensive care unit in a low-income country.

PMID- 28768536
TI  - A novel composite formulation of palmitoylethanolamide and quercetin decreases
      inflammation and relieves pain in inflammatory and osteoarthritic pain models.
AB  - BACKGROUND: Osteoarthritis (OA) is a common progressive joint disease in dogs and
      cats. The goal of OA treatment is to reduce inflammation, minimize pain, and
      maintain joint function. Currently, non-steroidal anti-inflammatory drugs (e.g.,
      meloxicam) are the cornerstone of treatment for OA pain, but side effects with
      long-term use pose important challenges to veterinary practitioners when dealing
      with OA pain. Palmitoylethanolamide (PEA) is a naturally-occurring fatty acid
      amide, locally produced on demand by tissues in response to stress. PEA
      endogenous levels change during inflammatory and painful conditions, including
      OA, i.e., they are typically increased during acute conditions and decreased in
      chronic inflammation. Systemic treatment with PEA has anti-inflammatory and pain
      relieving effects in several disorders, yet data are lacking in OA. Here we
      tested a new composite, i.e., PEA co-ultramicronized with the natural antioxidant
      quercetin (PEA-Q), administered orally in two different rat models of
      inflammatory and OA pain, namely carrageenan paw oedema and sodium
      monoiodoacetate (MIA)-induced OA. Oral treatment with meloxicam was used as
      benchmark. RESULTS: PEA-Q decreased inflammatory and hyperalgesic responses
      induced by carrageenan injection, as shown by: (i) paw oedema reduction, (ii)
      decreased severity in histological inflammatory score, (iii) reduced activity of
      myeloperoxidase, i.e., a marker of inflammatory cell infiltration, and (iv)
      decreased thermal hyperalgesia. Overall PEA-Q showed superior effects compared to
      meloxicam. In MIA-treated animals, PEA-Q exerted the following effects: (i)
      reduced mechanical allodynia and improved locomotor function, (ii) protected
      cartilage against MIA-induced histological damage, and (iii) counteracted the
      increased serum concentration of tumor necrosis factor alpha, interleukin 1 beta,
      metalloproteases 1, 3, 9 and nerve growth factor. The magnitude of these effects
      was comparable to, or even greater than, those of meloxicam. CONCLUSION: The
      present findings shed new light on some of the inflammatory and nociceptive
      pathways and mediators targeted by PEA-Q and confirm its anti-inflammatory and
      pain-relieving effects in rodent OA pain models. The translatability of these
      observations to canine and feline OA pain is currently under investigation.

PMID- 28768539
TI  - Comprehensive in silico allergenicity assessment of novel protein engineered
      chimeric Cry proteins for safe deployment in crops.
AB  - BACKGROUND: Development of chimeric Cry toxins by protein engineering of known
      and validated proteins is imperative for enhancing the efficacy and broadening
      the insecticidal spectrum of these genes. Expression of novel Cry proteins in
      food crops has however created apprehensions with respect to the safety aspects.
      To clarify this, premarket evaluation consisting of an array of analyses to
      evaluate the unintended effects is a prerequisite to provide safety assurance to
      the consumers. Additionally, series of bioinformatic tools as in silico aids are
      being used to evaluate the likely allergenic reaction of the proteins based on
      sequence and epitope similarity with known allergens. RESULTS: In the present
      study, chimeric Cry toxins developed through protein engineering were evaluated
      for allergenic potential using various in silico algorithms. Major emphasis was
      on the validation of allergenic potential on three aspects of paramount
      significance viz., sequence-based homology between allergenic proteins,
      validation of conformational epitopes towards identification of food allergens
      and physico-chemical properties of amino acids. Additionally, in vitro analysis
      pertaining to heat stability of two of the eight chimeric proteins and pepsin
      digestibility further demonstrated the non-allergenic potential of these chimeric
      toxins. CONCLUSIONS: The study revealed for the first time an all-encompassing
      evaluation that the recombinant Cry proteins did not show any potential
      similarity with any known allergens with respect to the parameters generally
      considered for a protein to be designated as an allergen. These novel chimeric
      proteins hence can be considered safe to be introgressed into plants.

PMID- 28768538
TI  - Pulsed radiofrequency or anterior neurectomy for anterior cutaneous nerve
      entrapment syndrome (ACNES) (the PULSE trial): study protocol of a randomized
      controlled trial.
AB  - BACKGROUND: Some patients with chronic abdominal pain suffer from an anterior
      cutaneous nerve entrapment syndrome (ACNES). This somewhat illusive syndrome is
      thought to be caused by the entrapment of end branches of the intercostal nerves
      residing in the abdominal wall. If ACNES is suspected, a local injection of an
      anesthetic agent may offer relief. If pain is recurrent following multiple
      injection therapy, an anterior neurectomy entailing removal of the entrapped
      nerve endings may be considered. After 1 year, a 70% success rate has been
      reported. Research on minimally invasive alternative treatments is scarce. Pulsed
      radiofrequency (PRF) treatment is a relatively new treatment for chronic pain
      syndromes. An electromagnetic field is applied around the nerve in the hope of
      leading to pain relief. This randomized controlled trial compares the effect of
      PRF treatment and neurectomy in patients with ACNES. METHODS: Adult ACNES
      patients having short-lived success following injections are randomized to PRF or
      neurectomy. At the 8-week follow-up visit, unsuccessful PRF patients are allowed
      to cross over to a neurectomy. Primary outcome is pain relief after either
      therapy. Secondary outcomes include patient satisfaction, quality of life, use of
      analgesics and unanticipated adverse events. The study is terminated 6 months
      after receiving the final procedure. DISCUSSION: Since academic literature on
      minimally invasive techniques is lacking, well-designed trials are needed to
      optimize results of treatment for ACNES. This is the first large, randomized
      controlled, proof-of-concept trial comparing two therapy techniques in ACNES
      patients. The first patient was included in October 2015. The expected trial
      deadline is December 2017. If effective, PRF may be incorporated into the ACNES
      treatment algorithm, thus minimizing the number of patients requiring surgery.
      TRIAL REGISTRATION: Nederlands Trial Register (Dutch Trial Register), NTR5131 (
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5131 ). Registered on
      15 April 2015.

PMID- 28768533
TI  - Progression of pathology in PINK1-deficient mouse brain from splicing via
      ubiquitination, ER stress, and mitophagy changes to neuroinflammation.
AB  - BACKGROUND: PINK1 deficiency causes the autosomal recessive PARK6 variant of
      Parkinson's disease. PINK1 activates ubiquitin by phosphorylation and cooperates
      with the downstream ubiquitin ligase PARKIN, to exert quality control and control
      autophagic degradation of mitochondria and of misfolded proteins in all cell
      types. METHODS: Global transcriptome profiling of mouse brain and neuron cultures
      were assessed in protein-protein interaction diagrams and by pathway enrichment
      algorithms. Validation by quantitative reverse transcriptase polymerase chain
      reaction and immunoblots was performed, including human neuroblastoma cells and
      patient primary skin fibroblasts. RESULTS: In a first approach, we documented
      Pink1-deleted mice across the lifespan regarding brain mRNAs. The expression
      changes were always subtle, consistently affecting "intracellular membrane
      bounded organelles". Significant anomalies involved about 250 factors at age 6
      weeks, 1300 at 6 months, and more than 3500 at age 18 months in the cerebellar
      tissue, including Srsf10, Ube3a, Mapk8, Creb3, and Nfkbia. Initially, mildly
      significant pathway enrichment for the spliceosome was apparent. Later, highly
      significant networks of ubiquitin-mediated proteolysis and endoplasmic reticulum
      protein processing occurred. Finally, an enrichment of neuroinflammation factors
      appeared, together with profiles of bacterial invasion and MAPK signaling changes
      while mitophagy had minor significance. Immunohistochemistry showed pronounced
      cellular response of Iba1-positive microglia and GFAP-positive astrocytes; brain
      lipidomics observed increases of ceramides as neuroinflammatory signs at old age.
      In a second approach, we assessed PINK1 deficiency in the presence of a stressor.
      Marked dysregulations of microbial defense factors Ifit3 and Rsad2 were
      consistently observed upon five analyses: (1) Pink1 -/- primary neurons in the
      first weeks after brain dissociation, (2) aged Pink1 -/- midbrain with transgenic
      A53T-alpha-synuclein overexpression, (3) human neuroblastoma cells with PINK1
      knockdown and murine Pink1 -/- embryonal fibroblasts undergoing acute starvation,
      (4) triggering mitophagy in these cells with trifluoromethoxy carbonylcyanide
      phenylhydrazone (FCCP), and (5) subjecting them to pathogenic RNA-analogue
      poly(I:C). The stress regulation of MAVS, RSAD2, DDX58, IFIT3, IFIT1, and LRRK2
      was PINK1 dependent. Dysregulation of some innate immunity genes was also found
      in skin fibroblast cells from PARK6 patients. CONCLUSIONS: Thus, an individual
      biomarker with expression correlating to progression was not identified. Instead,
      more advanced disease stages involved additional pathways. Hence, our results
      identify PINK1 deficiency as an early modulator of innate immunity in neurons,
      which precedes late stages of neuroinflammation during alpha-synuclein spreading.

PMID- 28768540
TI  - In vivo and in vitro performance of a China-made hemodialysis machine: a multi
      center prospective controlled study.
AB  - OBJECTIVE: To evaluate the in vivo and in vitro performance of a China-made
      dialysis machine (SWS-4000). METHODS: This was a multi-center prospective
      controlled study consisting of both long-term in vitro evaluations and cross-over
      in vivo tests in 132 patients. The China-made SWS-4000 dialysis machine was
      compared with a German-made dialysis machine (Fresenius 4008) with regard to Kt/V
      values, URR values, and dialysis-related adverse reactions in patients on
      maintenance hemodialysis, as well as the ultrafiltration rate, the concentration
      of electrolytes in the proportioned dialysate, the rate of heparin injection, the
      flow rate of the blood pump, and the rate of malfunction. RESULTS: The Kt/V and
      URR values at the 1st and 4th weeks of dialysis as well as the incidence of
      adverse effects did not differ between the two groups in cross-over in vivo tests
      (P > 0.05). There were no significant differences between the two groups in the
      error values of the ultrafiltration rate, the rate of heparin injection or the
      concentrations of electrolytes in the proportioned dialysate at different time
      points under different parameter settings. At weeks 2 and 24, with the flow rate
      of the blood pump set at 300 mL/min, the actual error of the SWS-4000 dialysis
      machine was significantly higher than that of the Fresenius 4008 dialysis machine
      (P < 0.05), but there was no significant difference at other time points or under
      other settings (P > 0.05). The malfunction rate was higher in the SWS-4000 group
      than in the Fresenius 4008 group (P < 0.05). CONCLUSIONS: The in vivo performance
      of the SWS-4000 dialysis machine is roughly comparable to that of the Fresenius
      4008 dialysis machine; however, the malfunction rate of the former is higher than
      that of the latter in in vitro tests. The stability and long-term accuracy of the
      SWS-4000 dialysis machine remain to be improved.

PMID- 28768541
TI  - Key populations and human rights in the context of HIV services rendition in
      Ghana.
AB  - BACKGROUND: In line with its half century old penal code, Ghana currently
      criminalizes and penalizes behaviors of some key populations - populations deemed
      to be at higher risk of acquiring or transmitting Human Immunodeficiency Virus
      (HIV). Men who have sex with men (MSM), and sex workers (SWs) fit into this
      categorization. This paper provides an analysis of how enactment and
      implementation of rights-limiting laws not only limit rights, but also amplify
      risk and vulnerability to HIV in key and general populations. The paper derives
      from a project that assessed the ethics sensitivity of key documents guiding
      Ghana's response to its HIV epidemic. Assessment was guided by leading frameworks
      from public health ethics, and relevant articles from the international bill of
      rights. DISCUSSION: Ghana's response to her HIV epidemic does not adequately
      address the rights and needs of key populations. Even though the national
      response has achieved some public health successes, palpable efforts to address
      rights issues remain nascent. Ghana's guiding documents for HIV response include
      no advocacy for decriminalization, depenalization or harm reduction approaches
      for these key populations. The impact of rights-restricting codes on the nation's
      HIV epidemic is real: criminalization impedes key populations' access to HIV
      prevention and treatment services. Given that they are bridging populations,
      whatever affects the Ghanaian key populations directly, affects the general
      population indirectly. The right to the highest attainable standard of health,
      without qualification, is generally acknowledged as a fundamental human right.
      Unfortunately, this right currently eludes the Ghanaian SW and MSM. The paper
      endorses decriminalization as a means of promoting this right. In the face of
      opposition to decriminalization, the paper proposes specific harm reduction
      strategies as approaches to promote health and uplift the diminished rights of
      key populations. Thus the authors call on Ghana to remove impediments to public
      health services provision to these populations. Doing so will require political
      will and sufficient planning toward prioritizing HIV prevention, care and
      treatment programming for key populations.

PMID- 28768542
TI  - Early rigorous control interventions can largely reduce dengue outbreak
      magnitude: experience from Chaozhou, China.
AB  - BACKGROUND: Dengue fever is a severe public heath challenge in south China. A
      dengue outbreak was reported in Chaozhou city, China in 2015. Intensified
      interventions were implemented by the government to control the epidemic.
      However, it is still unknown the degree to which intensified control measures
      reduced the size of the epidemics, and when should such measures be initiated to
      reduce the risk of large dengue outbreaks developing? METHODS: We selected
      Xiangqiao district as study setting because the majority of the indigenous cases
      (90.6%) in Chaozhou city were from this district. The numbers of daily indigenous
      dengue cases in 2015 were collected through the national infectious diseases and
      vectors surveillance system, and daily Breteau Index (BI) data were reported by
      local public health department. We used a compartmental dynamic SEIR
      (Susceptible, Exposed, Infected and Removed) model to assess the effectiveness of
      control interventions, and evaluate the control effect of intervention timing on
      dengue epidemic. RESULTS: A total of 1250 indigenous dengue cases was reported
      from Xiangqiao district. The results of SEIR modeling using BI as an indicator of
      actual control interventions showed a total of 1255 dengue cases, which is close
      to the reported number (n = 1250). The size and duration of the outbreak were
      highly sensitive to the intensity and timing of interventions. The more rigorous
      and earlier the control interventions implemented, the more effective it yielded.
      Even if the interventions were initiated several weeks after the onset of the
      dengue outbreak, the interventions were shown to greatly impact the prevalence
      and duration of dengue outbreak. CONCLUSIONS: This study suggests that early
      implementation of rigorous dengue interventions can effectively reduce the
      epidemic size and shorten the epidemic duration.

PMID- 28768543
TI  - The gap in human resources to deliver the guaranteed package of prevention and
      health promotion services at urban and rural primary care facilities in Mexico.
AB  - BACKGROUND: The purpose of this study was to estimate the gap between the
      available and the ideal supply of human resources (physicians, nurses, and health
      promoters) to deliver the guaranteed package of prevention and health promotion
      services at urban and rural primary care facilities in Mexico. METHODS: We
      conducted a cross-sectional observational study using a convenience sample. We
      selected 20 primary health facilities in urban and rural areas in 10 states of
      Mexico. We calculated the available and the ideal supply of human resources in
      these facilities using estimates of time available, used, and required to deliver
      health prevention and promotion services. We performed descriptive statistics and
      bivariate hypothesis testing using Wilcoxon and Friedman tests. Finally, we
      conducted a sensitivity analysis to test whether the non-normal distribution of
      our time variables biased estimation of available and ideal supply of human
      resources. RESULTS: The comparison between available and ideal supply for urban
      and rural primary health care facilities reveals a low supply of physicians. On
      average, primary health care facilities are lacking five physicians when they
      were estimated with time used and nine if they were estimated with time required
      (P < 0.05). No difference was observed between available and ideal supply of
      nurses in either urban or rural primary health care facilities. There is a
      shortage of health promoters in urban primary health facilities (P < 0.05).
      CONCLUSION: The available supply of physicians and health promoters is lower than
      the ideal supply to deliver the guaranteed package of prevention and health
      promotion services. Policies must address the level and distribution of human
      resources in primary health facilities.

PMID- 28768544
TI  - Preoperative endoscopic titanium clip placement facilitates intraoperative
      localization of early-stage esophageal cancer or severe dysplasia.
AB  - BACKGROUND: Accurate intraoperative localization of esophageal lesions is
      essential for successful surgical resection. We tested whether preoperative
      endoscopic placement of titanium clips could facilitate intraoperative
      localization of early-stage esophageal cancer or severe dysplasia. METHODS: A
      prospective randomized clinical trial was performed between May 2012 and July
      2014. All enrolled patients received preoperative endoscopy and esophageal
      endoscopic ultrasound, as well as pathological study on the biopsy specimen, to
      confirm early stage esophageal cancer or severe dysplasia. One day before the
      surgical operation, patients in the experimental group received the preoperative
      endoscopic titanium labeling of esophageal lesions. Then, during the surgical
      operation, palpitation of titanium clips was used to localize the lesions in
      these patients. In patients in the control group, palpitation of nodules or
      esophageal wall mucosal thickening, together with the consideration of the
      results from preoperative endoscopic and ultrasound studies, was applied to
      estimate the location of the esophageal lesions. Study outcomes included the
      proportions of patients having successful intraoperative pre-resection lesion
      localization, post-esophagectomy lesion visualization, negative upper surgical
      margin, change of surgical approaches, and positive postoperative pathological
      diagnosis. RESULTS: A total of 27 patients were enrolled into the study, with 14
      in the experimental group and 13 in the control group. Compared to the patients
      in the control group, a higher proportion of patients in the experimental group
      had statistically significant successful intraoperative esophageal lesion
      localization (100 versus 15.3% in the experimental versus control group).
      CONCLUSIONS: Preoperative endoscopic titanium clip placement could facilitate
      intraoperative localization of early-stage esophageal cancer or severe dysplasia.
      TRIAL REGISTRATION: Current study was registered in Chinese Clinical Trial
      Registry and World Health Organization International Clinical Trials Registry
      Platform, ChiCTR-INR-17010949 . Registered 22 March 2017, retrospectively
      registered.

PMID- 28768546
TI  - Five years' experience of an annual course on implementation science: an
      evaluation among course participants.
AB  - BACKGROUND: Increasing interest in implementation science has generated a demand
      for education and training opportunities for researchers and practitioners in the
      field. However, few implementation science courses have been described or
      evaluated in the scientific literature. The aim of the present study was to
      provide a short- and long-term evaluation of the implementation training at
      Linkoping University, Sweden. METHODS: Two data collections were carried out. In
      connection with the final seminar, a course evaluation form, including six items
      on satisfaction and suggestions for improvement, was distributed to the course
      participants, a total of 101 students from 2011 to 2015 (data collection 1),
      response rate 72%. A questionnaire including six items was distributed by e-mail
      to the same students in autumn 2016 (data collection 2), response rate 63%. Data
      from the two data collections were presented descriptively and analysed using the
      Kirkpatrick model consisting of four levels: reaction, learning, behaviour and
      results. RESULTS: The students were very positive immediately after course
      participation, rating high on overall perception of the course and the contents
      (reaction). The students also rated high on achievement of the course objectives
      and considered their knowledge in implementation science to be very good and to a
      high degree due to course participation (learning). Knowledge gained from the
      course was viewed to be useful (behaviour) and was applied to a considerable
      extent in research projects and work apart from research activities (results).
      CONCLUSIONS: The evaluation of the doctoral-level implementation science course
      provided by Linkoping University showed favourable results, both in the short and
      long term. The adapted version of the Kirkpatrick model was useful because it
      provided a structure for evaluation of the short- and long-term learning
      outcomes.

PMID- 28768547
TI  - Assisting an Australian Aboriginal and Torres Strait Islander person with
      gambling problems: a Delphi study.
AB  - BACKGROUND: Gambling problems appear to be more prevalent in the Australian
      Aboriginal and Torres Strait Islander population than in the non-Indigenous
      population. Although gambling harms can be significant, treatment-seeking rates
      are low. The Delphi expert consensus method was used to develop a set of
      guidelines on how a family or community member can assist an Aboriginal or Torres
      Strait Islander person with gambling problems. METHODS: Building on a previous
      systematic review of websites, books and journal articles a questionnaire was
      developed that contained items about the knowledge, skills and actions needed for
      supporting an Aboriginal or Torres Strait Islander person with gambling problems.
      These items were rated over three rounds by an expert panel comprising
      professionals who provide treatment to or conduct research with Aboriginal and
      Torres Strait Islander people with gambling problems. RESULTS: A total of 22
      experts rated 407 helping statements according to whether they thought the
      statements should be included in these guidelines. There were 225 helping
      statements that were endorsed by at least 90% of participants. These endorsed
      statements were used to develop the guidelines. CONCLUSION: Experts were able to
      reach substantial consensus on how someone can recognise the signs of gambling
      problems and support an Aboriginal or Torres Strait Islander person to change.

PMID- 28768548
TI  - The Anticoagulated trauma patient in the age of the direct oral anticoagulants: a
      Canadian perspective.
AB  - BACKGROUND: The anticoagulated trauma patient presents a particular challenge to
      the critical care physician. Our understanding of these patients is defined and
      extrapolated by experience with patients on warfarin pre-injury. Today, many
      patients who would have been on warfarin are now prescribed the Direct Oral
      Anticoagulants (DOACs) a class of anticoagulants with entirely different
      mechanisms of action, effects on routine coagulation assays and approach to
      reversal. METHODS: Trauma registry data from Toronto's (Ontario, Canada) two
      Level 1 trauma centres were used to identify patients on oral anticoagulation pre
      injury from June 1, 2014 to June 1, 2015. The trauma registry and medical records
      were reviewed and used to extract demographic and clinical data. RESULTS: We
      found 81 patients were on oral anticoagulants pre-injury representing 3.2% of the
      total trauma population and 33% of the orally anticoagulated patients were
      prescribed a DOAC prior to presentation. Comparison between the DOAC and warfarin
      groups showed similar age, mechanisms of injury, indications for anticoagulation,
      injury severity score and rate of intracranial hemorrhage. Patients on DOACs had
      higher initial mean hemoglobin vs warfarin (131 vs 120) and lower serum
      creatinine (94.8 vs 129.5). The percentage of patients receiving a blood
      transfusion in the trauma bay and total in-hospital transfusion was similar
      between the two groups however patients on DOACs were more likely to receive
      tranexamic acid vs patients on warfarin (32.1% vs 9.1%) and less likely to
      receive prothrombin concentrates (18.5% vs 60%). Patients on DOACs were found to
      have higher survival to discharge (92%) vs patients on warfarin (72%).
      CONCLUSION: Patients on DOACs pre-injury now represent a significant proportion
      of the anticoagulated trauma population. Although they share demographic and
      clinical similarities with patients on warfarin, patients on DOACs may have
      improved outcomes despite lack of established drug reversal protocols and
      challenging interpretation of coagulation assays. LEVEL OF EVIDENCE: III; Study
      Type: Retrospective Review.

PMID- 28768550
TI  - Abuse and disrespect in childbirth process and abortion situation in Latin
      America and the Caribbean-systematic review protocol.
AB  - BACKGROUND: Studies show that a large number of women around the world have
      experienced situations of abuse, disrespect, abuse, and neglect during childbirth
      and/or abortion. This violence is a serious violation of the rights of women,
      especially because it is a period in which the woman is more physiologically,
      socially, and psychologically vulnerable. Although this type of violence is
      known, there is still no international consensus on the definition of such
      violence and its prevalence is not known. In this sense, this systematic review
      aims (1) to find quantitative data about abuse and disrespect in obstetric care
      (delivery and/or abortion) in Latin America and the Caribbean to estimate the
      average prevalence of this type of abuse and (2) to identify interventions
      including programs, laws, and regulations-which have been implemented to prevent
      or respond to abuse and disrespect in childbirth process and abortion situation,
      evaluating its effectiveness on a global scale. METHODS: For this, we will use a
      refined and pre-established strategy to search databases such as PubMed, Embase,
      LILACS, and Scielo, and the studies found will pass through a selection process
      to complete the screening stage. DISCUSSION: Data will be extracted using
      standardized forms with the following information: scope of study, sample
      characteristics, objectives, design, data collection, methods of analysis, data
      source, and results. Considering the heterogeneity of the definitions of abuse,
      disrespect, and mistreatment of women in labor or abortion, it may not be
      possible to carry out the meta-analysis of the frequency of events reported in
      the included articles. Events reported by the original articles will be
      classified according to a typology of abuse, disrespect, and maltreatment in the
      labor or abortion process described by Bohren et al. (PLoS Med, 2015). SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42016038651.

PMID- 28768549
TI  - Intranasal insulin reverts central pathology and cognitive impairment in diabetic
      mother offspring.
AB  - BACKGROUND: Adverse effects in diabetic mothers offspring (DMO) are a major
      concern of increasing incidence. Among these, chronic central complications in
      DMO remain poorly understood, and in extreme cases, diabetes can essentially
      function as a gestational brain insult. Nevertheless, therapeutic alternatives
      for DMO are limited. METHODS: Therefore, we have analyzed the central long-term
      complications in the offspring from CD1 diabetic mothers treated with
      streptozotozin, as well as the possible reversion of these alterations by insulin
      administration to neonates. Brain atrophy, neuronal morphology, tau
      phosphorylation, proliferation and neurogenesis were assessed in the short term
      (P7) and in the early adulthood (10 weeks) and cognitive function was also
      analyzed in the long-term. RESULTS: Central complications in DMO were still
      detected in the adulthood, including cortical and hippocampal thinning due to
      synaptic loss and neuronal simplification, increased tau hyperphosphorylation,
      and diminished cell proliferation and neurogenesis. Additionally, maternal
      diabetes increased the long-term susceptibility to spontaneous central bleeding,
      inflammation and cognition impairment in the offspring. On the other hand,
      intracerebroventricular insulin administration to neonates significantly reduced
      observed alterations. Moreover, non-invasive intranasal insulin reversed central
      atrophy and tau hyperphosphorylation, and rescued central proliferation and
      neurogenesis. Vascular damage, inflammation and cognitive alterations were also
      comparable to their counterparts born to nondiabetic mice, supporting the utility
      of this pathway to access the central nervous system. CONCLUSIONS: Our data
      underlie the long-term effects of central complications in DMO. Moreover,
      observed improvement after insulin treatment opens the door to therapeutic
      alternatives for children who are exposed to poorly controlled gestational
      diabetes, and who may benefit from more individualized treatments.

PMID- 28768545
TI  - TREM2 in Neurodegenerative Diseases.
AB  - TREM2 variants have been identified as risk factors for Alzheimer's disease (AD)
      and other neurodegenerative diseases (NDDs). Because TREM2 encodes a receptor
      exclusively expressed on immune cells, identification of these variants
      conclusively demonstrates that the immune response can play an active role in the
      pathogenesis of NDDs. These TREM2 variants also confer the highest risk for
      developing Alzheimer's disease of any risk factor identified in nearly two
      decades, suggesting that understanding more about TREM2 function could provide
      key insights into NDD pathology and provide avenues for novel immune-related NDD
      biomarkers and therapeutics. The expression, signaling and function of TREM2 in
      NDDs have been extensively investigated in an effort to understand the role of
      immune function in disease pathogenesis and progression. We provide a
      comprehensive review of our current understanding of TREM2 biology, including new
      insights into the regulation of TREM2 expression, and TREM2 signaling and
      function across NDDs. While many open questions remain, the current body of
      literature provides clarity on several issues. While it is still often cited that
      TREM2 expression is decreased by pro-inflammatory stimuli, it is now clear that
      this is true in vitro, but inflammatory stimuli in vivo almost universally
      increase TREM2 expression. Likewise, while TREM2 function is classically
      described as promoting an anti-inflammatory phenotype, more than half of
      published studies demonstrate a pro-inflammatory role for TREM2, suggesting that
      its role in inflammation is much more complex. Finally, these components of TREM2
      biology are applied to a discussion of how TREM2 impacts NDD pathologies and the
      latest assessment of how these findings might be applied to immune-directed
      clinical biomarkers and therapeutics.

PMID- 28768552
TI  - A mild form of adenylosuccinate lyase deficiency in absence of typical brain MRI
      features diagnosed by whole exome sequencing.
AB  - BACKGROUND: Adenylosuccinate lyase (ADSL) deficiency is a defect of purine
      metabolism affecting purinosome assembly and reducing metabolite fluxes through
      purine de novo synthesis and purine nucleotide recycling pathways. The disorder
      shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The
      most severe form is characterized by neonatal encephalopathy, absence of
      spontaneous movement, respiratory failure, intractable seizures, and early death
      within the first weeks of life. More commonly, ADSL presents purely neurologic
      clinical picture characterized by severe psychomotor retardation, microcephaly,
      early onset of seizures, and autistic features (type I) or a more slowly
      progressing form with later onset, and major features including slight to
      moderate psychomotor retardation, and transient contact disturbances (type II).
      Diagnostic markers are the presence of succinylaminoimidazole carboxamide
      riboside (SAICAr) and succinyladenosine (SAdo) in extracellular fluids. ADSL is a
      rare disorder, although its prevalence remains unknown. Of note, the wide range
      of essentially nonspecific manifestations and lack of awareness of the condition
      often prevent diagnosis. CASE PRESENTATION: We present here the case of
      particularly mild, late onset ADSL that has been unsuccessfully investigated
      until whole exome sequencing (WES) was performed. CONCLUSIONS: Besides
      emphasizing the valuable diagnostic value of WES, this report provides new data
      further documenting the relatively wide clinical manifestation of ADSL.

PMID- 28768554
TI  - Letter to the Editor: Is poor sleep, and loneliness linked by increased use of
      technology?

PMID- 28768551
TI  - Feed-additive probiotics accelerate yet antibiotics delay intestinal microbiota
      maturation in broiler chicken.
AB  - BACKGROUND: Reducing antibiotics overuse in animal agriculture is one key in
      combat against the spread of antibiotic resistance. Probiotics are a potential
      replacement of antibiotics in animal feed; however, it is not clear whether and
      how probiotics and antibiotics differ in impact on physiology and microbial
      ecology of host animals. RESULTS: Host phenotype and fecal microbiota of broilers
      with either antibiotics or probiotics as feed additive were simultaneously
      sampled at four time points from birth to slaughter and then compared. Probiotic
      feeding resulted in a lower feed conversion ratio (FCR) and induced the highest
      level of immunity response, suggesting greater economic benefits in broiler
      farming. Probiotic use but not antibiotic use recapitulated the characteristics
      of age-dependent development of gut microbiota in the control group. The
      maturation of intestinal microbiota was greatly accelerated by probiotic feeding,
      yet significantly retarded and eventually delayed by antibiotic feeding. LP-8
      stimulated the growth of many intestinal Lactobacillus spp. and led to an altered
      bacterial correlation network where Lactobacillus spp. are negatively correlated
      with 14 genera and positively linked with none, yet from the start antibiotic
      feeding featured a less-organized network where such inter-genera interactions
      were fewer and weaker. Consistently, microbiota-encoded functions as revealed by
      metagenome sequencing were highly distinct between the two groups. Thus,
      "intestinal microbiota maturation index" was proposed to quantitatively compare
      impact of feed additives on animal microecology. CONCLUSIONS: Our results reveal
      a tremendous potential of probiotics as antibiotics' substitute in poultry
      farming.

PMID- 28768553
TI  - Comparative in vitro evaluation of contact activity of fluralaner, spinosad,
      phoxim, propoxur, permethrin and deltamethrin against the northern fowl mite,
      Ornithonyssus sylviarum.
AB  - BACKGROUND: Northern fowl mites (Ornithonyssus sylviarum) are obligate
      hematophagous ectoparasites of both feral birds and poultry, particularly chicken
      layers and breeders. They complete their entire life-cycle on infested birds
      while feeding on blood. Infestations of O. sylviarum are difficult to control and
      resistance to some chemical classes of acaricides is a growing concern. The
      contact susceptibility of O. sylviarum to a new active ingredient, fluralaner,
      was evaluated, as well as other compounds representative of the main chemical
      classes commonly used to control poultry mite infestations in Europe and the USA.
      METHODS: Six acaricides (fluralaner, spinosad, phoxim, propoxur, permethrin,
      deltamethrin) were dissolved and serially diluted in butanol:olive oil (1:1) to
      obtain test solutions used for impregnation of filter paper packets. A carrier
      only control was included. Thirty adult northern fowl mites, freshly collected
      from untreated host chickens, were inserted into each packet for continuous
      compound exposure. Mite mortality was assessed after incubation of the test
      packets for 48 h at 75% relative humidity and a temperature of 22  degrees C.
      RESULTS: Adult mite LC50 /LC99 values were 2.95/8.09 ppm for fluralaner,
      1587/3123 ppm for spinosad, 420/750 ppm for phoxim and 86/181 ppm for propoxur.
      Permethrin and deltamethrin LC values could not be calculated due to lack of
      mortality observed even at 1000 ppm. CONCLUSIONS: Northern fowl mites were highly
      sensitive to fluralaner after contact exposure. They were moderately sensitive to
      phoxim and propoxur, and less sensitive to spinosad. Furthermore, the tested mite
      population appeared to be resistant to the pyrethroids, permethrin and
      deltamethrin, despite not being exposed to acaricides for at least 10 years.

PMID- 28768555
TI  - Is there any relationship between right and left hand dominance and right and
      left nasal airflow dominance?
AB  - BACKGROUND: Left- or right-handedness is a common human trait, and it has been
      previously reported that human nasal airflow dominance correlates with hand
      dominance. Any relationship between hand dominance and nasal airflow dominance
      would be unusual. This study aimed to measure nasal airflow and look for any
      relationship to handedness. METHODS: The modified Glatzel mirror was used to
      record the dominant nasal passage at 15-minute intervals over a 6-hour period in
      29 healthy participants consisting of 15 left-handers and 14 right-handers.
      RESULTS: In left-handers, the percentage of time that the left nasal passage was
      dominant ranged from 0 to 100 per cent. In right-handers, the percentage of time
      that the right nasal passage was dominant ranged from 4.2 to 95.8 per cent. No
      correlation between nasal airflow dominance and hand dominance was identified.
      CONCLUSION: The results do not support the hypothesis that nasal airflow and
      handedness are related.

PMID- 28768556
TI  - Estimation of the transmission dynamics of African swine fever virus within a
      swine house.
AB  - The spread of African swine fever virus (ASFV) threatens to reach further parts
      of Europe. In countries with a large swine production, an outbreak of ASF may
      result in devastating economic consequences for the swine industry. Simulation
      models can assist decision makers setting up contingency plans. This creates a
      need for estimation of parameters. This study presents a new analysis of a
      previously published study. A full likelihood framework is presented including
      the impact of model assumptions on the estimated transmission parameters. As
      animals were only tested every other day, an interpretation was introduced to
      cover the weighted infectiousness on unobserved days for the individual animals
      (WIU). Based on our model and the set of assumptions, the within- and between-pen
      transmission parameters were estimated to beta w = 1.05 (95% CI 0.62-1.72), beta
      b = 0.46 (95% CI 0.17-1.00), respectively, and the WIU = 1.00 (95% CI 0-1).
      Furthermore, we simulated the spread of ASFV within a pig house using a modified
      SEIR-model to establish the time from infection of one animal until ASFV is
      detected in the herd. Based on a chosen detection limit of 2.55% equivalent to 10
      dead pigs out of 360, the disease would be detected 13-19 days after
      introduction.

PMID- 28768557
TI  - The high frequency of non-aspartic acid residues at HA222 in influenza A(H1N1)
      2009 pandemic viruses is associated with mortality during the upsurge of 2015: a
      molecular and epidemiological study from central India.
AB  - Influenza A(H1N1) viruses of the 2009 pandemic (A(H1N1)pdm09) continue to cause
      outbreaks in the post-pandemic period. During January to May 2015, an upsurge of
      influenza was recorded that resulted in high fatality in central India. Genetic
      lineage, mutations in the hemagglutinin (HA) gene and infection by quasi-species
      are reported to affect disease severity. The objective of this study is to
      present the molecular and epidemiological trends during the 2015 influenza
      outbreak in central India. All the referred samples were subjected to qRT-PCR for
      diagnosis. HA gene sequencing (23 survivors and 24 non-survivors) and cloning
      were performed and analyzed using Molecular Evolutionary Genomic Analyzer (MEGA
      5.05). Of the 3625 tested samples, 1607 (44.3%) were positive for influenza
      A(H1N1)pdm09, of which 228 (14.2%) individuals succumbed to death. A significant
      trend was observed in positivity (P = 0.003) and mortality (P < 0.0001) with
      increasing age. The circulating A(H1N1)pdm09 virus was characterized as belonging
      to clade-6B. Clinically significant mutations were detected. Patients infected
      with the quasi-species of the virus had a greater risk of death (P = 0.009). This
      study proposes a robust molecular and clinical surveillance program for the
      detection and characterization of the virus, along with prompt treatment
      protocols to prevent outbreaks.

PMID- 28768558
TI  - Chlamydia gallinacea: a widespread emerging Chlamydia agent with zoonotic
      potential in backyard poultry.
AB  - Chlamydia gallinacea, a new chlamydial agent, has been reported in four European
      countries as well as Argentina and China. Experimentally infected chickens with
      C. gallinacea in previous study showed no clinical signs but had significantly
      reduced gains in body weight (6.5-11.4%). Slaughterhouse workers exposed to
      infected chickens have developed atypical pneumonia, indicating C. gallinacea is
      likely a zoonotic agent. In this study, FRET-PCR confirmed that C. gallinacea was
      present in 12.4% (66/531) of oral-pharyngeal samples from Alabama backyard
      poultry. Phylogenetic comparisons based on ompA variable domain showed that 16
      sequenced samples represented 14 biotypes. We report for the first time the
      presence of C. gallinacea in North America, and this warrants further research on
      the organism's pathogenicity, hosts, transmission, and zoonotic potential.

PMID- 28768559
TI  - MALDI-TOF MS protein profiling for the rapid identification of Chagas disease
      triatomine vectors and application to the triatomine fauna of French Guiana.
AB  - Triatomines are haematophagous insects involved in the transmission of
      Trypanosoma cruzi, the aetiological agent of Chagas disease. The vector
      competence of these arthropods can be highly variable, depending on the species.
      A precise identification is therefore crucial for the epidemiological
      surveillance of T. cruzi and the determination of at-risk human populations. To
      circumvent the difficulties of morphological identification and the lack of
      comprehensiveness of the GenBank database, we hereby propose an alternative
      method for triatomine identification. The femurs of the median legs of
      triatomines from eight different species from French Guiana were subjected to
      matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis.
      Method evaluation was performed on fresh specimens and was applied to dry
      specimens collected between 1991 and 2003. Femur-derived protein extracts
      provided reproducible spectra within the same species along with significant
      interspecies heterogeneity. Validation of the study by blind test analysis
      provided 100% correct identification of the specimens in terms of the species,
      sex and developmental stage. MALDI-TOF mass spectrometry appears to be a powerful
      tool for triatomine identification, which is a major step forward in the fight
      against Chagas disease.

PMID- 28768560
TI  - Transmission dynamics of lumpy skin disease in Ethiopia.
AB  - Lumpy skin disease (LSD) is a severe disease of cattle caused by a Capripoxvirus
      and often caused epidemics in Ethiopia and many other countries. This study was
      undertaken to quantify the transmission between animals and to estimate the
      infection reproduction ratio in a predominantly mixed crop-livestock system and
      in intensive commercial herd types. The transmission parameters were based on a
      susceptible-infectious-recovered (SIR) epidemic model with environmental
      transmission and estimated using generalized linear models. The transmission
      parameters were estimated using a survival rate of infectious virus in the
      environment equal to 0.325 per day, a value based on the best-fitting statistical
      model. The transmission rate parameter between animals was 0.072 (95% CI 0.068
      0.076) per day in the crop-livestock production system, whereas this transmission
      rate in intensive production system was 0.076 (95% CI 0.068-0.085) per day. The
      reproduction ratio (R) of LSD between animals in the crop-livestock production
      system was 1.07, whereas it was 1.09 between animals in the intensive production
      system. The calculated R provides a baseline against which various control
      options can be assessed for efficacy.

PMID- 28768561
TI  - Field application of MALDI-TOF MS on mosquito larvae identification.
AB  - In recent years, matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) has emerged as an efficient tool for arthropod
      identification. Its application for field monitoring of adult mosquitoes was
      demonstrated, but identification of larvae has been limited to laboratory-reared
      specimens. Study aim was to test the success of MALDI-TOF MS in correctly
      identifying mosquito larvae collected in the field. Collections were performed at
      13 breeding sites in urban areas of Marseille, a city in the South of France. A
      total of 559 larvae were collected. Of these, 73 were accurately morphologically
      identified, with confirmation either by molecular identification (n = 31) or
      analysis with MALDI-TOF MS (n = 31) and 11 were tested using both methods. The
      larvae identified belonged to six species including Culiseta longiareolata, Culex
      pipiens pipiens, Culex hortensis, Aedes albopictus, Ochlerotatus caspius and
      Anopheles maculipennis. A high intra-species reproducibility and inter-species
      specificity of whole larva MS spectra was obtained and was independent of
      breeding site. More than 92% of the remaining 486 larvae were identified in blind
      tests against the MS spectra database. Identification rates were lower for early
      and pupal stages, which is attributed to lower protein abundance and
      metamorphosis, respectively. The suitability of MALDI-TOF MS for mosquito larvae
      identification from the field has been confirmed.

PMID- 28768562
TI  - Does a better adherence to dietary guidelines reduce mortality risk and
      environmental impact in the Dutch sub-cohort of the European Prospective
      Investigation into Cancer and Nutrition?
AB  - Guidelines for a healthy diet aim to decrease the risk of chronic diseases. It is
      unclear as to what extent a healthy diet is also an environmentally friendly
      diet. In the Dutch sub-cohort of the European Prospective Investigation into
      Cancer and Nutrition, the diet was assessed with a 178-item FFQ of 40 011
      participants aged 20-70 years between 1993 and 1997. The WHO's Healthy Diet
      Indicator (HDI), the Dietary Approaches to Stop Hypertension (DASH) score and the
      Dutch Healthy Diet index 2015 (DHD15-index) were investigated in relation to
      greenhouse gas (GHG) emissions, land use and all-cause mortality risk. GHG
      emissions were associated with HDI scores (-3.7 % per sd increase (95 % CI -3.4, 
      4.0) for men and -1.9 % (95 % CI -0.4, -3.4) for women), with DASH scores in
      women only (1.1 % per sd increase, 95 % CI 0.9, 1.3) and with DHD15-index scores
      (-2.5 % per sd increase (95 % CI -2.2, -2.8) for men and -2.0 % (95 % CI -1.9, 
      2.2) for women). For all indices, higher scores were associated with less land
      use (ranging from -1.3 to -3.1 %). Mortality risk decreased with increasing
      scores for all indices. Per sd increase of the indices, hazard ratios for
      mortality ranged from 0.88 (95 % CI 0.82, 0.95) to 0.96 (95 % CI 0.92, 0.99). Our
      results showed that adhering to the WHO and Dutch dietary guidelines will lower
      the risk of all-cause mortality and moderately lower the environmental impact.
      The DASH diet was associated with lower mortality and land use, but because of
      high dairy product consumption in the Netherlands it was also associated with
      higher GHG emissions.

PMID- 28768563
TI  - Infant feeding decisions and behaviours among low-income smoke-exposed women:
      timing and change during pregnancy.
AB  - OBJECTIVE: The present study aimed to describe change in feeding intentions and
      predictors of breast-feeding intentions during the course of pregnancy. DESIGN:
      Analysis of prospectively collected data from a larger randomized controlled
      trial of a health education intervention to reduce environmental smoke exposure
      among women during and after pregnancy. SETTING: Participants were recruited from
      prenatal clinics, but all further communication occurred with participating women
      living in the community. SUBJECTS: Low-income, adult women (n 399) were
      interviewed during the 16th and 32nd week of pregnancy to ascertain prenatal
      feeding intentions and breast-feeding knowledge, attitudes and self-efficacy.
      Characteristics of women by infant feeding intention were assessed along with
      differences in intention from 16 to 32 weeks of pregnancy and feeding behaviours
      after delivery. Differences in psychosocial variables between women of different
      intention for infant feeding were measured. Women in each category of feeding
      intention were assessed for changes in psychosocial factors by eventual infant
      feeding behaviour. RESULTS: Feeding intention early in pregnancy was strongly,
      but not consistently, associated with feeding intention late in pregnancy,
      feeding initiation and later feeding patterns. Over one-third of women who were
      undecided at 16 weeks' gestation or earlier initiated breast-feeding. Increases
      in knowledge and improvement in time, social factors and social support barriers
      were found among those who exclusively breast-fed. CONCLUSIONS: Results indicate
      that feeding decisions may change during pregnancy. Determining when women make
      feeding decisions during their pregnancy warrants more research. Interventions to
      increase breast-feeding intentions should target knowledge, self-efficacy and
      barriers.

PMID- 28768564
TI  - Exploring beliefs about dietary supplement use: focus group discussions with
      Dutch adults.
AB  - OBJECTIVE: Although dietary supplement use is increasing in Europe and the USA,
      little research involving adults' beliefs regarding dietary supplements has been
      conducted. Therefore, the present study aimed to explore and compare users' and
      non-users' beliefs towards dietary supplements. DESIGN: Thirteen focus group
      discussions were conducted of which seven groups were dietary supplement users
      and six groups were non-users. Based on the socio-cognitive factors of the
      Integrated Change Model, a semi-structured topic guide was set up. The
      discussions were audio-recorded and subjected to qualitative content analysis,
      applying the framework approach. SETTING: Data were collected in Maastricht, the
      Netherlands, in 2014 and 2015. SUBJECTS: In total fifty-six individuals
      participated in the study, of whom twenty-eight were dietary supplement users and
      twenty-eight non-users. The average age of participants was 42.9 years. RESULTS:
      Dietary supplement users' attitude beliefs were mainly related to mental and
      physical health enhancement, illness prevention and curative health benefits.
      Users were critical of the nutritional knowledge of health professionals and of
      the quality of food products. Non-users were convinced that the human body does
      not need any support and that regular food is enough to cover one's nutritional
      needs. Users and non-users held comparable beliefs regarding the definition and
      risks of dietary supplements, and perceived social influences. CONCLUSIONS: In
      their decision about dietary supplement use, both groups were guided by their own
      convictions to a great extent. Both groups would benefit from improved
      understanding of the health effects of dietary supplements to improve informed
      decision making.

PMID- 28768565
TI  - Caspase-2 mediates triglyceride (TG)-induced macrophage cell death.
AB  - Triglyceride (TG) accumulation causes macrophage cell death, which affects the
      development of atherosclerosis. Here, we examined whether caspase-2 is implicated
      in TG-induced macrophage cell death. We found that caspase-2 activity is
      increased in TG-treated THP-1 macrophages, and that inhibition of caspase-2
      activity drastically inhibits TG-induced cell death. We previously reported that
      TG-induced macrophage cell death is triggered by caspase-1, and thus investigated
      the relationship between caspase-2 and caspase-1 in TG-induced macrophage cell
      death. Inhibition of caspase-2 activity decreased caspase-1 activity in TG
      treated macrophages. However, caspase-1 inhibition did not affect caspase-2
      activity, suggesting that caspase-2 is upstream of caspase-1. Furthermore, we
      found that TG induces activation of caspase-3, -7, -8, and -9, as well as
      cleavage of PARP. Inhibition of caspase-2 and -1 decreased TG-induced caspase-3, 
      7, -8, and -9 activation and PARP cleavage. Taken together, these results suggest
      that TG-induced macrophage cell death is mediated via the caspase-2/caspase
      1/apoptotic caspases/PARP pathways. [BMB Reports 2017; 50(10): 510-515].

PMID- 28768566
TI  - Dead cell phagocytosis and innate immune checkpoint.
AB  - The human body loses several billions of cells daily. When cells die in vivo, the
      corpse of each dead cell is immediately cleared. Specifically, dead cells are
      efficiently recognized and cleared by multiple types of neighboring phagocytes.
      Early research on cell death focused more on molecular mechanisms of cell death
      regulation while the cellular corpses were merely considered cellular debris.
      However, it has come to light that various biological stimuli following cell
      death are important for immune regulation. Clearance of normal dead cells occurs
      silently in immune tolerance. Exogenous or mutated antigens of malignant or
      infected cells can initiate adaptive immunity, thereby inducing immunogenicity by
      adjuvant signals. Several pathogens and cancer cells have strategies to limit the
      adjuvant signals and escape immune surveillance. In this review, we present an
      overview of the mechanisms of dead cell clearance and its immune regulations.
      [BMB Reports 2017; 50(10): 496-503].

PMID- 28768567
TI  - In vitro growth and development of isolated secondary follicles from vitrified
      caprine ovarian cortex.
AB  - The aim of this study was to evaluate the viability, antrum formation and in
      vitro development of isolated secondary follicles from vitrified caprine ovarian
      cortex in a medium previously established for fresh isolated secondary follicles,
      in the absence (alpha-minimum essential medium (alpha-MEM+) alone) or presence of
      FSH and vascular endothelial growth factor (VEGF; alpha-MEM++FSH+VEGF). Ovarian
      fragments were distributed among five treatments (T1 to T5): fresh follicles were
      fixed immediately (T1), follicles from fresh tissue were cultured in vitro in
      alpha-MEM+ (T2) or alpha-MEM++FSH+VEGF (T3) and follicles from vitrified tissue
      were cultured in vitro in alpha-MEM+ (T4) or alpha-MEM++FSH+VEGF (T5). After 6
      days of culture, treated follicles (T2, T3, T4 and T5) were evaluated for
      morphology, viability and follicular development (growth, antrum formation and
      proliferation of granulosa cells by Ki67 and argyrophilic nucleolar organiser
      region (AgNOR) staining). The levels of reactive oxygen species (ROS) in the
      culture media were also assessed. Overall, morphology of vitrified follicles was
      altered (P<0.05) compared with the fresh follicles. Follicular viability, antrum
      formation and ROS were similar between treatments (P>0.05). The average overall
      and daily follicular growth was highest (P<0.05) in T3. Granulosa cells in all
      treatments (T1, T2, T3, T4 and T5) stained positive for Ki67. However, fresh
      follicles from T3 had significantly higher AgNOR staining (P<0.05) compared with
      follicles of T1, T2, T4 and T5. In conclusion, secondary follicles can be
      isolated from vitrified and warmed ovarian cortex and survive and form an antrum
      when growing in an in vitro culture for 6 days.

PMID- 28768568
TI  - Changes in urinary androgen concentration indicate that male giant pandas
      (Ailuropoda melanoleuca) respond to impending female oestrus during and outside
      the typical spring breeding season.
AB  - Giant pandas have been described as mono-oestrus spring breeders, yet males
      exposed to aseasonal oestrous females in the autumn or winter exhibit breeding
      behaviours and interest in mating. In the present study, urinary androgens and
      sperm parameters were quantified for males exposed to females expressing oestrus
      during spring, autumn or winter to examine plasticity of reproductive seasonality
      in giant pandas. Monthly average androgen concentrations for two males exposed to
      females in either seasonal or aseasonal oestrus were greater (P<0.001) than
      baseline concentrations. Evaluation of daily androgen concentrations revealed a
      peak that was three- to fivefold greater than baseline, occurring an average of 5
      days before ovulation for both seasonal and aseasonal cycles. There were no
      significant differences in testes volume, sperm motility, forward progression or
      sperm concentration in males between female seasonal and aseasonal cycle years.
      Male gonadal activity was more variable without a clear pattern in years when the
      female was anovulatory than when she was ovulatory (seasonal or aseasonal). These
      data show the flexible reproductive capacity of male giant pandas as demonstrated
      by a rapid physiological readiness to mate in response to female oestrous cues
      within or outside the normal breeding season and may suggest a facultative
      seasonal reproduction with a 'female-induced rut'.

PMID- 28768569
TI  - Tissue cell stress response to obesity and its interaction with late gestation
      diet.
AB  - Intrauterine growth restriction in late pregnancy can contribute to adverse long
      term metabolic health in the offspring. In the present study we used an animal
      (sheep) model of maternal dietary manipulation in late pregnancy, combined with
      exposure of the offspring to a low-activity, obesogenic environment after
      weaning, to characterise the effects on glucose homeostasis. Dizygotic twin
      pregnant sheep were either fed to 60% of requirements (nutrient restriction (R))
      or fed ad libitum (~140% of requirements (A)) from 110 days gestation until term
      (~147 days). After weaning (~3 months of age), the offspring were kept in either
      a standard (in order to remain lean) or low-activity, obesogenic environment. R
      mothers gained less weight and produced smaller offspring. As adults, obese
      offspring were heavier and fatter with reduced glucose tolerance, regardless of
      maternal diet. Molecular markers of stress and autophagy in liver and adipose
      tissue were increased with obesity, with gene expression of hepatic glucose
      related protein 78 (Grp78) and omental activation transcription factor 6 (Atf6),
      Grp78 and ER stress degradation enhancer molecule 1 (Edem1) only being increased
      in R offspring. In conclusion, the adverse effect of juvenile-onset obesity on
      insulin-responsive tissues can be amplified by previous exposure to a suboptimal
      nutritional environment in utero, thereby contributing to earlier onset of
      insulin resistance.

PMID- 28768570
TI  - Primary cytoreductive surgery and adjuvant hormonal monotherapy in women with
      advanced low-grade serous ovarian carcinoma: Reducing overtreatment without
      compromising survival?
AB  - OBJECTIVES: Women with advanced-stage, low-grade serous ovarian carcinoma (LGSC)
      have low chemotherapy response rates and poor overall survival. Most LGSC tumors
      overexpress hormone receptors, which represent a potential treatment target. Our
      study objective was to determine the outcomes of patients with advanced-stage
      LGSC treated with primary cytoreductive surgery (CRS) and hormone therapy (HT).
      METHODS: A retrospective study was performed at two academic cancer centers.
      Patients with Stage II-IV LGSC underwent either primary or interval CRS followed
      by adjuvant HT between 2004 and 2016. Gynecologic pathologists reviewed all
      cases. Two-year progression-free (PFS) and overall survival (OS) were calculated.
      RESULTS: Twenty-seven patients were studied; primary CRS followed by HT were
      administered in 26, while 1 patient had neoadjuvant chemotherapy followed by CRS
      and HT. The median patient age was 47.5, and patients had Stage II (n=2), Stage
      IIIA (n=6), Stage IIIC (n=18), and Stage IV (n=1) disease. Optimal cytoreduction
      to no gross residual was achieved in 85.2%. Ninety six percent of tumors
      expressed estrogen receptors, while only 32% expressed progesterone receptors.
      Letrozole was administered post operatively in 55.5% cases, anastrozole in 37.1%
      and tamoxifen in 7.4%. After a median follow up of 41months, only 6 patients
      (22.2%) have developed a tumor recurrence and two patients have died of disease.
      Median PFS and OS have not yet been reached, but 2-year PFS and OS were 82.8% and
      96.3%, respectively, and 3-year PFS and OS were 79.0% and 92.6%, respectively.
      CONCLUSIONS: Our series describes the initial experience with cytoreductive
      surgery and hormonal monotherapy for women with Stage II-IV primary ovarian LGSC.
      While surgery remains the mainstay of treatment, chemotherapy may not be
      necessary in patients with advanced-stage disease who receive adjuvant hormonal
      therapy. A cooperative group, Phase III trial is planned to define the optimal
      therapy for women with this ovarian carcinoma subtype.

PMID- 28768572
TI  - Comment on "Maternal and perinatal outcomes in pregnancy-associated melanoma.
      Report of two cases and a systematic literature review".

PMID- 28768571
TI  - A double-plating approach to distal femur fracture: A clinical study.
AB  - BACKGROUND: Locked plating is one of the latest innovative options for treating
      supracondylar femur fractures with relatively low failure rates. Single lateral
      plating was often found to have a relative higher failure rate. No clinical
      studies of double-plating distal femur fixation have thus far been reported. The
      aim of this study is to present our clinical experience with this surgical
      approach. PATIENTS AND METHODS: Thirty-two patients (26 females and 6 males, mean
      age 76 years, range 44-101) were included in the study. Eight of them patients
      had a periprosthetic stable implant fracture and two patients were treated for a
      nonunion. RESULTS: All fractures, excluding one that needed bone grafting and one
      refracture, healed within 12 weeks. One patient needed bone grafting for delayed
      union and one patient needed fixation exchange due to femur re-fracture at the
      site of the most proximal screw. Two patients developed superficial wound
      infection and one patient required medial plate removal after union due to deep
      infection. CONCLUSIONS: Based on these promising results, we propose that the
      double-plating technique should be considered in the surgeon's armamentarium for
      the treatment of supracondylar femur fractures, particularly in patients with
      poor bone quality, comminuted fractures and very low periprosthetic fractures.

PMID- 28768574
TI  - Patient inaccessibility to antifungal drugs in developing nations: The case of
      Pakistan.

PMID- 28768573
TI  - Violence exposure and adolescents' same-day obesogenic behaviors: New findings
      and a replication.
AB  - OBJECTIVE: To test whether exposure to violence is associated with same-day
      increases in obesogenic behaviors among young adolescents, including unhealthy
      food and beverage consumption, poor quality sleep, and lack of physical activity.
      METHODS: Young at-risk adolescents between 12 and 15 years of age were recruited
      via telephone screening from low-income neighborhoods. Adolescents and their
      parents completed in-person assessments, followed by Ecological Momentary
      Assessment (EMA) delivered to 151 adolescents' mobile phones three times a day
      for 30 days (4329 person days). Three obesogenic behaviors - unhealthy food
      consumption, poor sleep quality, and lack of physical activity - and violence
      exposure were assessed daily. Adolescents' body mass index (BMI) was assessed
      prior to the EMA and 18 months later. A replication was performed among 395
      adolescents from a population-representative sample (with 5276 EMA person days).
      RESULTS: On days that at-risk adolescents were exposed versus not exposed to
      violence, they were more likely to consume unhealthy foods and beverages (b =
      0.12, p = 0.01), report feeling tired the next morning (OR = 1.58, p < 0.01), and
      to be active (OR = 1.61, p < 0.01). At-risk adolescents who reported higher
      consumption of soda and caffeinated beverages during the 30-day EMA were more
      likely to experience increases in BMI in later adolescence. Findings related to
      sleep and activity were supported in the population-based replication sample;
      however, no significant same-day associations were found between violence
      exposure and unhealthy dietary consumption. CONCLUSIONS: This study provides
      evidence that exposure to violence is associated with same-day unhealthy dietary
      consumption among at-risk adolescents and next-day tiredness related to sleep
      quality among adolescents from both at-risk and normative populations. Findings
      also point to unhealthy soda consumption during early adolescence as an important
      predictor of weight gain among at-risk adolescents.

PMID- 28768575
TI  - Short-term results of the management of severe bone defects in primary TKA with
      cement and K-wires.
AB  - OBJECTIVE: The aim of this study was to evaluate the results of cement and
      kirschner wire augmentation in the management of bone defects in primary TKA.
      METHODS: Twenty-four patients (10 male, 14 female; mean age: 66 years) with
      uncontained unilateral medial tibial articular bone defect who underwent TKA
      between 2010 and 2014 were included in this study. The average follow up time was
      33.7 months. Patients were divided to two groups according to the size of the
      bone defect (Group 1: <20 mm, Group 2: >20 mm). The tibial defect was
      reconstructed by using cement and K-wires. We used posterior stabilized
      prosthesis with no tibial stem extension. RESULTS: The preoperative and
      postoperative lower extremity mechanical axis in Group I was in a mean varus of
      15 degrees  and mean varus of 3 degrees , respectively (p < 0.001). The
      preoperative and postoperative lower extremity mechanical axis in Group 2 was in
      a mean varus of 20 degrees  and mean varus of 3 degrees  respectively in Group II
      (p < 0.001). None of the patients neither suffered from failure of K-wires nor
      loosening. CONCLUSION: The use of cement and K-wires augmentation appears to be a
      simple and cost-effective treatment option for the tibial bone defects in primary
      TKA. LEVEL OF EVIDENCE: Level IV, Therapeutic study.

PMID- 28768576
TI  - The xenobiotic sensor PXR in a marine flatfish species (Solea senegalensis): Gene
      expression patterns and its regulation under different physiological conditions.
AB  - The pregnane X receptor (PXR) is a nuclear receptor belonging to the NR1I sub
      family and a known master regulator of xenobiotic metabolism. New roles have been
      recently proposed in mammals through its activation by vitamin K (VK) such as
      regulation of glucose metabolism, bone homeostasis, reproduction, neuronal
      development and cognitive capacities. In marine fish species little is known
      about PXR and its potential roles. Here, expression patterns of pxr transcripts
      and conservation of protein domains were determined in the Senegalese sole (Solea
      senegalensis), a marine flatfish model species in aquatic ecotoxicology. In
      addition to a full coding sequence transcript (sspxr1), two variants lacking DNA
      and/or ligand binding domains (sspxr2 and sspxr3) were also identified. The
      expression of sspxr1 during early development and in adult tissues was
      ubiquitous, but highest levels were observed in liver, intestine and skin.
      Expression was also detected by in situ hybridization in chondrocytes and cells
      from the granular and inner nuclear layers in three month old fish. Finally,
      sspxr1 expression was shown to be differentially regulated under physiological
      conditions related with fasting, VK and warfarin metabolism. The present work
      provides new and basic knowledge regarding pxr sequence and expression patterns
      in a marine flatfish species to unveil the potential impact of xenobiotics on
      marine fish physiology, and will allow a better and more ecosystemic
      environmental risk assessment of different pollutants over the marine
      environments with the development of reporter assays using PXR sequences from
      evolutionary distantly marine species (such as vertebrate and invertebrate marine
      species).

PMID- 28768577
TI  - Microplastics in livers of European anchovies (Engraulis encrasicolus, L.).
AB  - Microplastics (MPs) are thought to be ingested by a wide range of marine
      organisms before being excreted. However, several studies in marine organisms
      from different taxa have shown that MPs and nanoplastics could be translocated in
      other organs. In this study, we investigated the presence of MPs in the livers of
      commercial zooplanktivorous fishes collected in the field. The study focuses
      mainly on the European anchovy Engraulis encrasicolus but concerns also the
      European pilchard Sardina pilchardus and the Atlantic herring Clupea harengus.
      Two complementary methodologies were used to attest the occurrence of MPs in the
      hepatic tissue and to exclude contamination. 1) MPs were isolated by degradation
      of the hepatic tissue. 2) Cryosections were made on the livers and observed in
      polarized light microscopy. Both methods separately revealed that MPs, mainly
      polyethylene (PE), were translocated into the livers of the three clupeid
      species. In anchovy, 80 per cent of livers contained relatively large MPs that
      ranged from 124 MUm to 438 MUm, showing a high level of contamination. Two
      translocation pathways are hypothesized: (i) large particles found in the liver
      resulted from the agglomeration of smaller pieces, and/or (ii) they simply pass
      through the intestinal barrier. Further studies are however required to
      understand the exact process.

PMID- 28768578
TI  - The use of inhaled corticosteroids in chronically ventilated preterm infants.
AB  - Bronchopulmonary dysplasia (BPD) is the most usual reason for preterm infants to
      require chronic mechanical ventilation. Inflammation is a key factor underlying
      the lung injury leading to the development of BPD, and the rationale for use of
      corticosteroids in the management of ventilator-dependent preterm infants is
      based on their anti-inflammatory effects. Because systemic corticosteroids are
      associated with significant adverse effects in preterm infants, attention has
      turned to the use of inhaled corticosteroids (ICS) as a potentially safer therapy
      for BPD. The aim of this review is to discuss what is known about the efficacy
      and safety of ICS in chronically ventilated preterm infants. However, this has
      been a challenge since there is a paucity of high-grade evidence for the use of
      ICS in these patients. Thus, there is a real need for well-powered randomized
      controlled trials examining short- and long-term outcomes of ICS use in this
      population.

PMID- 28768580
TI  - 2D-speckle tracking right ventricular strain to assess right ventricular systolic
      function in systolic heart failure. Analysis of the right ventricular free and
      posterolateral walls.
AB  - BACKGROUND: Right ventricular (RV) systolic function is a powerful prognostic
      factor in patients with systolic heart failure. The accurate estimation of RV
      function remains difficult. The aim of the study was to determine the diagnostic
      accuracy of 2D-speckle tracking RV strain in patients with systolic heart
      failure, analyzing both free and posterolateral walls. METHODS: Seventy-six
      patients with dilated cardiopathy (left ventricular end-diastolic
      volume>=75ml/m2) and left ventricular ejection fraction<=45% had an analysis of
      the RV strain. Feasibility, reproducibility and diagnostic accuracy of RV strain
      were analyzed and compared to other echocardiographic parameters of RV function.
      RV dysfunction was defined as a RV ejection fraction<=40% measured by
      radionuclide angiography. RESULTS: RV strain feasibility was 93.9% for the free
      wall and 79.8% for the posterolateral wall. RV strain reproducibility was good
      (intra-observer and inter-observer bias and limits of agreement of 0.16+/-1.2% [
      2.2-2.5] and 0.84+/-2.4 [-5.5-3.8], respectively). Patients with left heart
      failure have a RV systolic dysfunction that can be unmasked by advanced
      echocardiographic imaging: mean RV strain was -21+/-5.7% in patients without RV
      dysfunction and -15.8+/-5.1% in patients with RV dysfunction (p=0.0001). Mean RV
      strain showed the highest diagnostic accuracy to predict depressed RVEF (area
      under the curve (AUC) 0.75) with moderate sensitivity (60.5%) but high
      specificity (87.5%) using a cutoff value of -16%. CONCLUSIONS: RV strain seems to
      be a promising and more efficient measure than previous RV echocardiographic
      parameters for the diagnosis of RV systolic dysfunction.

PMID- 28768579
TI  - Untargeted metabolomics of fresh and heat treatment Tiger nut (Cyperus esculentus
      L.) milks reveals further insight into food quality and nutrition.
AB  - Tiger nut (Cyperus esculentus L.) is a crop traditionally grown in Valencia
      Region (Spain) and other temperate and tropical regions in the world, where its
      tubers are commonly consumed as tiger nut milk (horchata). Because of their
      nutritive potential and original taste, these products are beginning to spread
      internationally and, as consequence, analytical procedures to assess nutritional
      profiles, quality control issues are acquiring increasing relevance. The main
      objective of this study was to use an advance analytical method and chemometrics
      tools to determine if the ultra-high temperature (UHT) treatment necessary to
      extend the shelf life of tiger nut milk would affect the profile of nutrients
      when compared to fresh product. A cold solvent extraction followed by liquid
      chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS) was
      used. Datasets obtained from UHT and fresh tiger nut milk data were analyzed
      through an untargeted metabolomics approach to compare chemical patterns,
      highlighting differences in citric acid esters of mono- diglycerides (CITREM) and
      monoacylglycerol (MAG) used as emulsifiers of UHT products, and a remarkably
      higher abundance of biotin, phosphatidic acid (PA) and L-arginine in fresh
      products. These results showed that untargeted metabolomics through high
      resolution tandem mass spectrometry allowed fine differences between food
      products to be found, therefore, the nutrient lost caused by UHT treatment was
      clearly discerned.

PMID- 28768582
TI  - BLIND OVERNIGHT: A case of fulminant idiopathic intracranial hypertension.
AB  - Idiopathic Intracranial Hypertension (IIH) is a syndrome seen predominantly in
      obese women of reproductive age group, characterized by signs and symptoms of
      increased intracranial pressure due to an unknown cause. Some individuals have a
      more malignant form of disease called fulminant idiopathic intracranial
      hypertension with rapid worsening of symptoms over days. We report a case of
      33year-old obese female (BMI 36.9) who presented with a severe headache and
      blurred vision for one week, found to have idiopathic intracranial hypertension
      with rapid worsening of symptoms suggestive of a fulminant course of disease. She
      was managed with prompt surgical intervention. In patients with fulminant
      idiopathic intracranial hypertension, surgery such as cerebrospinal fluid
      shunting or optic nerve sheath fenestration should not be delayed to prevent
      vision loss.

PMID- 28768581
TI  - Cardiac defects, morbidity and mortality in patients affected by RASopathies.
      CARNET study results.
AB  - BACKGROUND: RASopathies are developmental disease caused by mutations in genes
      encoding for signal transducers of the RAS-MAPK cascade. The aim of the present
      study was to provide a comprehensive description of morbidity and mortality in
      patients with molecularly confirmed RASopathy. METHODS: A multicentric,
      observational, retrospective study was conducted in seven European cardiac
      centres participating to the CArdiac Rasopathy NETwork (CARNET). Clinical records
      of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed.
      Mortality was described as crude mortality, cumulative survival and restricted
      estimated mean survival. Multivariable regression analysis was used to assess the
      impact of mutated genes on number of interventions and overall prognosis.
      RESULTS: Cardiac defects occurred in 80.3% of cases, almost half of them
      underwent at least one intervention. Overall, crude mortality was 0.29/100
      patients-year. Cumulative survival was 98.8%, 98.2%, 97.7%, 94.3%, at 1, 5, 10,
      and 20years, respectively. Restricted estimated mean survival at 20years follow
      up was 19.6years. Ten patients died (2.7% of the entire cohort; 3.4% of patients
      with cardiac defect). Patients with hypertrophic cardiomyopathy (HCM) and age
      <2years or young adults, as well as subjects with biventricular obstruction and
      PTPN11 mutations had a higher risk of cardiac death. CONCLUSIONS: The risk of
      intervention was higher in individuals with Noonan syndrome and pulmonary
      stenosis carrying PTPN11 mutations. Overall, mortality was relatively low, even
      though the specific association between HCM, biventricular outflow tract
      obstructions and PTPN11 mutations appeared to be associated with early mortality,
      including immediate post-operative events and sudden death.

PMID- 28768583
TI  - The evaluation of the Clarus(r) Levitan fibre-optic stylet in a simulated
      cervical spine immobilisation.

PMID- 28768584
TI  - RTS and RTS-A have equal value in mortality prediction of patients with severely
      trauma.

PMID- 28768586
TI  - Targeted end point of CVP of 15mm Hg would be better than that of 12mm Hg in the
      patients with mechanical ventilation.

PMID- 28768587
TI  - New from APIC: ASC Intensive offers 4 days of concentrated training for
      ambulatory care practice settings.

PMID- 28768585
TI  - Procalcitonin in the Emergency Department: A potential expensive over-request
      that can be modulated through institutional protocols.

PMID- 28768588
TI  - Journal Club: Hand hygiene compliance in a universal gloving setting.

PMID- 28768589
TI  - Journal Club: Developing a user-friendly report for electronically assisted
      surveillance of catheter-associated urinary tract infections.
AB  - The article chosen for this Journal Club commentary describes the development and
      testing of a report format using automated data to report urinary catheter
      utilization and catheter-associated urinary tract infections (CAUTIs).1 This
      research sought to address a gap in knowledge regarding the optimal display and
      content of data reports, communicating to diverse audiences, which used
      surveillance data from Department of Veterans Affairs' electronic health records.
      The specific research aim of this project was to develop and pilot test report
      formats deemed usable and trustworthy by the end user, and discover the best way
      to deliver to the ideal audience automated data, which is formatted and presented
      in a way that is acceptable to the end user.

PMID- 28768590
TI  - Use of a patient empowerment tool for hand hygiene.
AB  - BACKGROUND: Patient empowerment is recognized as an important component of a
      multimodal strategy to improve hand hygiene adherence. We examined the attitudes
      of adult patients and parents of pediatric patients toward a new patient
      empowerment tool (PET) at our hospital. We also surveyed physicians to determine
      their perceptions about the PET. METHODS: A cross-sectional survey was performed
      of hospitalized children's parents and adult patients in a 531-bed tertiary care
      teaching hospital in West Virginia. Surveys were anonymous and self-administered.
      A separate survey was administered via e-mail to resident and attending
      physicians from the departments of internal medicine, pediatrics, and family
      medicine. RESULTS: Most parents and adult patients felt it was their role to
      speak up if a provider did not perform hand hygiene, but a smaller number
      actually felt comfortable using the PET. Only 54.9% of physicians felt that
      patients should be involved in reminding providers to perform hand hygiene.
      Overall, physicians indicated that they would prefer a patient to use words
      rather than the PET to remind them to perform hand hygiene. CONCLUSIONS: In our
      study, parents and adult patients supported use of the PET, but physicians were
      less supportive. As the patient empowerment movement grows, we should work to
      improve physician acceptance of patient involvement if it is to be successful.

PMID- 28768591
TI  - Hand hygiene compliance in a universal gloving setting.
AB  - BACKGROUND: The use of gloves for every patient contact (ie, universal gloving)
      has been suggested as an infection prevention adjunct and alternative to contact
      precautions. However, gloves may carry organisms unless they are changed
      properly. In addition, hand hygiene is required before donning and after removing
      gloves, and there are scarce data regarding glove changing and hand hygiene in a
      universal gloving setting. METHODS: This nonrandomized observational before-after
      study evaluated the effect of education and feedback regarding hand hygiene.
      Compliance with hand hygiene and glove use was directly observed in a universal
      gloving setting at a 10-bed intensive care unit in a Japanese tertiary care
      university teaching hospital. RESULTS: A total of 6,050 hand hygiene
      opportunities were identified. Overall, hand hygiene compliance steadily
      increased from study period 1 (16.1%) to period 5 (56.8%), although there were
      indication-specific differences in the baseline compliance, the degree of
      improvement, and the reasons for noncompliance. There were decreases in the
      compliance with universal gloving and the incidence of methicillin-resistant
      Staphylococcus aureus. CONCLUSION: It is difficult to properly perform glove use
      and hand hygiene in a universal gloving setting, given its complexity. Direct
      observation with specific feedback and education may be effective in improving
      compliance.

PMID- 28768592
TI  - Effect of hand lotion on the effectiveness of hygienic hand antisepsis:
      Implications for practicing hand hygiene.
AB  - BACKGROUND: Skin protection products should be used after washing hands with
      soap, during breaks, after work, and during leisure time. Aside from their
      beneficial effects, skin care products may also interact with alcohol-based hand
      disinfectants by reducing their efficacy. The aim of this study was to
      investigate the effect of a hand lotion on the effectiveness of hygienic hand
      antisepsis using an alcohol-based handrub. METHODS: The effect of a protective
      hand lotion against an isopropyl alcohol-based handrub was investigated in 20
      healthy volunteers according to the European standard test procedure EN 1500 in
      the following combinations: handwashing and application of hand lotion, only
      application of hand lotion, and no washing and no hand lotion (control), each for
      5 minutes or 1 hour before hand antisepsis. The difference in microbiologic
      before-and-after values were expressed as log reduction factor. RESULTS: The
      effectiveness of hand antisepsis was not significantly affected in any of the
      groups using the tested hand lotion. CONCLUSIONS: Hand antisepsis may be delayed
      for 5 minutes after hand lotion application. Shorter time intervals might be
      possible but were not tested.

PMID- 28768593
TI  - Staff nurses as antimicrobial stewards: An integrative literature review.
AB  - BACKGROUND: Guidelines on antimicrobial stewardship emphasize the importance of
      an interdisciplinary team, but current practice focuses primarily on defining the
      role of infectious disease physicians and pharmacists; the role of inpatient
      staff nurses as antimicrobial stewards is largely unexplored. METHODS: An updated
      integrative review method guided a systematic appraisal of 13 articles spanning
      January 2007-June 2016. Quantitative and qualitative peer-reviewed publications
      including staff nurses and antimicrobial knowledge or stewardship were
      incorporated into the analysis. RESULTS: Two predominant themes emerged from this
      review: (1) nursing knowledge, education, and information needs; and (2) patient
      safety and organizational factors influencing antibiotic management. DISCUSSION:
      Focused consideration to empower and educate staff nurses in antimicrobial
      management is needed to strengthen collaboration and build an interprofessional
      stewardship workforce. CONCLUSIONS: Further exploration on the integration and
      measurement of nursing participation is needed to accelerate this important
      patient safety initiative.

PMID- 28768594
TI  - The interventions in the control group should not be ignored.

PMID- 28768595
TI  - Response to letter to the editor: Nebulized colistin in ventilator-associated
      pneumonia: Should we trust it?

PMID- 28768596
TI  - Letter to the editor: Extent of pleural effusion on chest radiograph is
      associated with failure of high-flow nasal cannula oxygen therapy.

PMID- 28768597
TI  - Diffusion-weighted imaging for cutaneous vascular anomalies.

PMID- 28768598
TI  - Mismatch negativity in preclinical models of schizophrenia.
AB  - Schizophrenia is a mental disorder associated with profoundly disruptive positive
      and negative symptomology that result in difficulties building close
      relationships with others, performing daily tasks and sustaining independent
      living, resulting in poor social, vocational and occupational attainment
      (functional outcome). Mismatch Negativity (MMN) is a change in the sensory event
      related potential that occurs in response to deviation from an established
      pattern of stimulation. Patients with schizophrenia show a reduction in MMN that
      is positively associated with impaired cognition and poor functional outcome.
      This has led to interest in MMN as a potential clinical and pre-clinical
      biomarker of fundamental neural processes responsible for reduced functional
      outcome. To date, relatively few studies have sought to assess MMN in non-human
      primates or rodents. The validity of these studies will be reviewed using
      criteria used to identify true deviance detection based MMN responses in human
      subjects. Although MMN has been difficult to establish in pre-clinical models the
      weight of evidence suggests that non-human animals show true deviance based MMN.

PMID- 28768599
TI  - Pre-onset risk characteristics for mania among young people at clinical high risk
      for psychosis.
AB  - INTRODUCTION: Psychosis and mania share conceptual, genetic and clinical
      features, which suggest the possibility that they have common antecedents.
      Participants identified to be at-risk for psychosis might also be at-risk for
      mania. We aimed to identify the rate and predictors of transition to mania in a
      cohort of youth with clinical or familial risk for psychosis. METHODS: Among a
      cohort of 416 young people with an at-risk mental state for psychosis defined
      using the Ultra-High-Risk (UHR) criteria, 74.7% were followed up between 5 and
      13years from their baseline assessment. We undertook a matched case-control
      examination of those who developed mania over the follow-up period compared to
      those who did not develop mania or psychosis. Transition to mania was determined
      using either a structured clinical interview, or diagnoses from a state-wide
      public mental health contact registry. Clinical characteristics and risk factors
      were examined at baseline using information from structured interviews, clinical
      file notes, rating scales and unstructured assessments. RESULTS: Eighteen
      participants developed mania (UHR-Manic transition or UHR-M, 4.3%). In comparison
      with participants matched on age, gender and baseline-study who developed neither
      mania nor psychosis, more UHR-M participants had subthreshold manic symptoms or
      were prescribed antidepressants at baseline. They also had lower global
      functioning. DISCUSSION: In addition to the UHR criteria, features such as
      subthreshold manic symptoms and antidepressant use may help identify at-risk
      groups that predict the onset of mania in addition to transition to psychosis.
      Presence of manic symptoms may also indicate syndrome specificity early in the
      prodromal phase.

PMID- 28768600
TI  - Promoting long-term functional improvement after cognitive remediation in
      schizophrenia.

PMID- 28768601
TI  - Translating cognitive behavioral interventions from bench to bedside: The
      feasibility and acceptability of cognitive remediation in research as compared to
      clinical settings.
AB  - : Cognitive remediation (CR) research typically addresses internal validity, and
      few studies consider CR in a real-world context. This study evaluated the fit
      between the program conditions and treatment model in research and clinical
      settings, with the goal of informing future research on the contextual challenges
      associated with the implementation of CR. Data was drawn from an initiative by
      New York State's Office of Mental Health (OMH), to implement CR programs for
      adults with Serious Mental Illness (SMI) in 16 state operated outpatient clinics.
      One of these clinics first became a research site for a CR randomized clinical
      trial, which allowed for a comparison of the feasibility and acceptability of CR
      in a research as compared to a clinical setting. RESULTS: The research site
      averaged almost triple the number of referrals as the clinical sites. Over nine
      months 46.51% of clinic referrals were enrolled in the CR program whereas 64.29%
      of research referrals were enrolled. Clinical site utilization averaged 70.53%
      while research site utilization averaged 90.47%. At the clinical sites, 97% of
      respondents reported CR was an excellent or good experience. There was high
      treatment fidelity for program structure and content across sites. CONCLUSIONS:
      This comparison of CR in clinical and research sites highlights the decrease in
      referrals, enrollment and utilization that occurs when a program moves from a
      highly controlled setting to the real world. Still, the acceptability, fill rates
      and utilization indicated that CR can be successfully implemented in large scale,
      geographically diverse, publically funded clinic settings.

PMID- 28768602
TI  - Completing the puzzle: The search for pieces in the understanding of psychosis
      risk in 22q11.2 deletion syndrome.

PMID- 28768603
TI  - Tick surveillance for Borrelia miyamotoi and phylogenetic analysis of isolates in
      Mongolia and Japan.
AB  - Borrelia miyamotoi, recently recognized as a human pathogenic spirochete, was
      isolated from Ixodes persulcatus and I. ovatus in northern Mongolia and Honshu
      Island, a major island in Japan. Although no human B. miyamotoi infections have
      been reported in Mongolia, the prevalence of B. miyamotoi in ticks from Mongolia
      is higher than that in ticks from Hokkaido, Japan, where human cases have been
      reported. Moreover, the multi-locus sequence analysis of cultured isolates
      revealed that B. miyamotoi isolates in Mongolia belong to the Siberian type, a
      sequence type that was originally reported from isolates from I. persulcatus in
      Hokkaido. Thus, there is a possibility of unrecognized human B. miyamotoi
      infections in Mongolia. Moreover our data support the hypothesis of clonal
      expansion of the Siberian type B. miyamotoi. In contrast, although the isolates
      were found to belong to the Siberian type B. miyamotoi, two isolates from I.
      persulcatus in Honshu Island were identified to be of a different sequence type.
      Furthermore, B. miyamotoi isolates from I. ovatus were distinguishable from those
      from I. ricinus complex ticks, according to genetic analysis. In this study, we
      show that there may be some genetic diversity among B. miyamotoi in ticks from
      Honshu Island.

PMID- 28768605
TI  - Cost-effectiveness of early identification of HIV infection.

PMID- 28768604
TI  - Cost-effectiveness of screening for HIV in primary care: a health economics
      modelling analysis.
AB  - BACKGROUND: Early HIV diagnosis reduces morbidity, mortality, the probability of
      onward transmission, and their associated costs, but might increase cost because
      of earlier initiation of antiretroviral treatment (ART). We investigated this
      trade-off by estimating the cost-effectiveness of HIV screening in primary care.
      METHODS: We modelled the effect of the four-times higher diagnosis rate observed
      in the intervention arm of the RHIVA2 randomised controlled trial done in
      Hackney, London (UK), a borough with high HIV prevalence (>=0.2% adult
      prevalence). We constructed a dynamic, compartmental model representing incidence
      of infection and the effect of screening for HIV in general practices in Hackney.
      We assessed cost-effectiveness of the RHIVA2 trial by fitting model diagnosis
      rates to the trial data, parameterising with epidemiological and behavioural data
      from the literature when required, using trial testing costs and projecting
      future costs of treatment. FINDINGS: Over a 40 year time horizon, incremental
      cost-effectiveness ratios were L22 201 (95% credible interval 12 662-132 452) per
      quality-adjusted life-year (QALY) gained, L372 207 (268 162-1 903 385) per death
      averted, and L628 874 (434 902-4 740 724) per HIV transmission averted. Under
      this model scenario, with UK cost data, RHIVA2 would reach the upper National
      Institute for Health and Care Excellence cost-effectiveness threshold (about L30
      000 per QALY gained) after 33 years. Scenarios using cost data from Canada (which
      indicate prolonged and even higher health-care costs for patients diagnosed late)
      suggest this threshold could be reached in as little as 13 years. INTERPRETATION:
      Screening for HIV in primary care has important public health benefits as well as
      clinical benefits. We predict it to be cost-effective in the UK in the medium
      term. However, this intervention might be cost-effective far sooner, and even
      cost-saving, in settings where long-term health-care costs of late-diagnosed
      patients in high-prevalence regions are much higher (>=60%) than those of
      patients diagnosed earlier. Screening for HIV in primary care is cost-effective
      and should be promoted. FUNDING: NHS City and Hackney, UK Department of Health,
      National Institute for Health Research Collaboration for Leadership in Applied
      Health Research and Care.

PMID- 28768606
TI  - The Potential of Mobile Apps for Improving Asthma Self-Management: A Review of
      Publicly Available and Well-Adopted Asthma Apps.
AB  - BACKGROUND: Effective disease self-management lowers asthma's burden of disease
      for both individual patients and health care systems. In principle, mobile health
      (mHealth) apps could enable effective asthma self-management interventions that
      improve a patient's quality of life while simultaneously reducing the overall
      treatment costs for health care systems. However, prior reviews in this field
      have found that mHealth apps for asthma lack clinical evaluation and are often
      not based on medical guidelines. Yet, beyond the missing evidence for clinical
      efficacy, little is known about the potential apps might have for improving
      asthma self-management. OBJECTIVE: The aim of this study was to assess the
      potential of publicly available and well-adopted mHealth apps for improving
      asthma self-management. METHODS: The Apple App store and Google Play store were
      systematically searched for asthma apps. In total, 523 apps were identified, of
      which 38 apps matched the selection criteria to be included in the review. Four
      requirements of app potential were investigated: app functions, potential to
      change behavior (by means of a behavior change technique taxonomy), potential to
      promote app use (by means of a gamification components taxonomy), and app quality
      (by means of the Mobile Application Rating Scale [MARS]). RESULTS: The most
      commonly implemented functions in the 38 reviewed asthma apps were tracking
      (30/38, 79%) and information (26/38, 68%) functions, followed by assessment
      (20/38, 53%) and notification (18/38, 47%) functions. On average, the reviewed
      apps applied 7.12 of 26 available behavior change techniques (standard deviation
      [SD]=4.46) and 4.89 of 31 available gamification components (SD=4.21). Average
      app quality was acceptable (mean=3.17/5, SD=0.58), whereas subjective app quality
      lied between poor and acceptable (mean=2.65/5, SD=0.87). Additionally, the sum
      scores of all review frameworks were significantly correlated (lowest
      correlation: r36=.33, P=.04 between number of functions and gamification
      components; highest correlation: r36=.80, P<.001 between number of behavior
      change techniques and gamification components), which suggests that an app's
      potential tends to be consistent across review frameworks. CONCLUSIONS: Several
      apps were identified that performed consistently well across all applied review
      frameworks, thus indicating the potential mHealth apps offer for improving asthma
      self-management. However, many apps suffer from low quality. Therefore, app
      reviews should be considered as a decision support tool before deciding which app
      to integrate into a patient's asthma self-management. Furthermore, several
      research-practice gaps were identified that app developers should consider
      addressing in future asthma apps.

PMID- 28768607
TI  - Peer Communication in Online Mental Health Forums for Young People: Directional
      and Nondirectional Support.
AB  - BACKGROUND: The Internet has the potential to help young people by reducing the
      stigma associated with mental health and enabling young people to access services
      and professionals which they may not otherwise access. Online support can empower
      young people, help them develop new online friendships, share personal
      experiences, communicate with others who understand, provide information and
      emotional support, and most importantly help them feel less alone and normalize
      their experiences in the world. OBJECTIVE: The aim of the research was to gain an
      understanding of how young people use an online forum for emotional and mental
      health issues. Specifically, the project examined what young people discuss and
      how they seek support on the forum (objective 1). Furthermore, it looked at how
      the young service users responded to posts to gain an understanding of how young
      people provided each other with peer-to-peer support (objective 2). METHODS:
      Kooth is an online counseling service for young people aged 11-25 years and
      experiencing emotional and mental health problems. It is based in the United
      Kingdom and provides support that is anonymous, confidential, and free at the
      point of delivery. Kooth provided the researchers with all the online forum posts
      between a 2-year period, which resulted in a dataset of 622 initial posts and
      3657 initial posts with responses. Thematic analysis was employed to elicit key
      themes from the dataset. RESULTS: The findings support the literature that online
      forums provide young people with both informational and emotional support around
      a wide array of topics. The findings from this large dataset also reveal that
      this informational or emotional support can be viewed as directive or
      nondirective. The nondirective approach refers to when young people provide
      others with support by sharing their own experiences. These posts do not include
      explicit advice to act in a particular way, but the sharing process is hoped to
      be of use to the poster. The directive approach, in contrast, involves
      individuals making an explicit suggestion of what they believe the poster should
      do. CONCLUSIONS: This study adds to the research exploring what young people
      discuss within online forums and provides insights into how these communications
      take place. Furthermore, it highlights the challenge that organizations may
      encounter in mediating support that is multidimensional in nature (informational
      emotional, directive-nondirective).

PMID- 28768608
TI  - Web-Based Medical Service: Technology Attractiveness, Medical Creditability,
      Information Source, and Behavior Intention.
AB  - BACKGROUND: Web-based medical service (WBMS), a cooperative relationship between
      medical service and Internet technology, has been called one of the most
      innovative services of the 21st century. However, its business promotion and
      implementation in the medical industry have neither been expected nor executed.
      Few studies have explored this phenomenon from the viewpoint of inexperienced
      patients. OBJECTIVE: The primary goal of this study was to explore whether
      technology attractiveness, medical creditability, and diversified medical
      information sources could increase users' behavior intention. METHODS: This study
      explored the effectiveness of web-based medical service by using three situations
      to manipulate sources of medical information. A total of 150 questionnaires were
      collected from people who had never used WBMS before. Hierarchical regression was
      used to examine the mediation and moderated-mediation effects. RESULTS: Perceived
      ease of use (P=.002) and perceived usefulness (P=.001) significantly enhance
      behavior intentions. Medical credibility is a mediator (P=.03), but the
      relationship does not significantly differ under diverse manipulative information
      channels (P=.39). CONCLUSIONS: Medical credibility could explain the extra
      variation between technology attractiveness and behavior intention, but not
      significant under different moderating effect of medical information sources.

PMID- 28768609
TI  - Toward Predicting Social Support Needs in Online Health Social Networks.
AB  - BACKGROUND: While online health social networks (OHSNs) serve as an effective
      platform for patients to fulfill their various social support needs, predicting
      the needs of users and providing tailored information remains a challenge.
      OBJECTIVE: The objective of this study was to discriminate important features for
      identifying users' social support needs based on knowledge gathered from survey
      data. This study also provides guidelines for a technical framework, which can be
      used to predict users' social support needs based on raw data collected from
      OHSNs. METHODS: We initially conducted a Web-based survey with 184 OHSN users.
      From this survey data, we extracted 34 features based on 5 categories: (1)
      demographics, (2) reading behavior, (3) posting behavior, (4) perceived roles in
      OHSNs, and (5) values sought in OHSNs. Features from the first 4 categories were
      used as variables for binary classification. For the prediction outcomes, we used
      features from the last category: the needs for emotional support, experience
      based information, unconventional information, and medical facts. We compared 5
      binary classifier algorithms: gradient boosting tree, random forest, decision
      tree, support vector machines, and logistic regression. We then calculated the
      scores of the area under the receiver operating characteristic (ROC) curve (AUC)
      to understand the comparative effectiveness of the used features. RESULTS: The
      best performance was AUC scores of 0.89 for predicting users seeking emotional
      support, 0.86 for experience-based information, 0.80 for unconventional
      information, and 0.83 for medical facts. With the gradient boosting tree as our
      best performing model, we analyzed the strength of individual features in
      predicting one's social support need. Among other discoveries, we found that
      users seeking emotional support tend to post more in OHSNs compared with others.
      CONCLUSIONS: We developed an initial framework for automatically predicting
      social support needs in OHSNs using survey data. Future work should involve
      nonsurvey data to evaluate the feasibility of the framework. Our study
      contributes to providing personalized social support in OHSNs.

PMID- 28768610
TI  - Behavior Change Techniques in Physical Activity eHealth Interventions for People
      With Cardiovascular Disease: Systematic Review.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of premature death
      and disability in Europe, accounting for 4 million deaths per year and costing
      the European Union economy almost ?196 billion annually. There is strong evidence
      to suggest that exercise-based secondary rehabilitation programs can decrease the
      mortality risk and improve health among patients with CVD. Theory-informed use of
      behavior change techniques (BCTs) is important in the design of cardiac
      rehabilitation programs aimed at changing cardiovascular risk factors. Electronic
      health (eHealth) is the use of information and communication technologies (ICTs)
      for health. This emerging area of health care has the ability to enhance self
      management of chronic disease by making health care more accessible, affordable,
      and available to the public. However, evidence-based information on the use of
      BCTs in eHealth interventions is limited, and particularly so, for individuals
      living with CVD. OBJECTIVE: The aim of this systematic review was to assess the
      application of BCTs in eHealth interventions designed to increase physical
      activity (PA) in CVD populations. METHODS: A total of 7 electronic databases,
      including EBSCOhost (MEDLINE, PsycINFO, Academic Search Complete, SPORTDiscus
      with Full Text, and CINAHL Complete), Scopus, and Web of Science (Core
      Collection) were searched. Two authors independently reviewed references using
      the software package Covidence (Veritas Health Innovation). The reviewers met to
      resolve any discrepancies, with a third independent reviewer acting as an
      arbitrator when required. Following this, data were extracted from the papers
      that met the inclusion criteria. Bias assessment of the studies was carried out
      using the Cochrane Collaboration's tool for assessing the risk of bias within
      Covidence; this was followed by a narrative synthesis. RESULTS: Out of the 987
      studies that were identified, 14 were included in the review. An additional 9
      studies were added following a hand search of review paper references. The
      average number of BCTs used across the 23 studies was 7.2 (range 1-19). The top
      three most frequently used BCTs included information about health consequences
      (78%, 18/23), goal setting (behavior; 74%, 17/23), and joint third, self
      monitoring of behavior and social support (practical) were included in 11 studies
      (48%, 11/23) each. CONCLUSIONS: This systematic review is the first to
      investigate the use of BCTs in PA eHealth interventions specifically designed for
      people with CVD. This research will have clear implications for health care
      policy and research by outlining the BCTs used in eHealth interventions for
      chronic illnesses, in particular CVD, thereby providing clear foundations for
      further research and developments in the area.

PMID- 28768611
TI  - A Smartphone App for Families With Preschool-Aged Children in a Public Nutrition
      Program: Prototype Development and Beta-Testing.
AB  - BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants, and
      Children (WIC) in the United States provides free supplemental food and nutrition
      education to low-income mothers and children under age 5 years. Childhood obesity
      prevalence is higher among preschool children in the WIC program compared to
      other children, and WIC improves dietary quality among low-income children. The
      Children Eating Well (CHEW) smartphone app was developed in English and Spanish
      for WIC-participating families with preschool-aged children as a home-based
      intervention to reinforce WIC nutrition education and help prevent childhood
      obesity. OBJECTIVE: This paper describes the development and beta-testing of the
      CHEW smartphone app. The objective of beta-testing was to test the CHEW app
      prototype with target users, focusing on usage, usability, and perceived barriers
      and benefits of the app. METHODS: The goals of the CHEW app were to make the WIC
      shopping experience easier, maximize WIC benefit redemption, and improve parent
      snack feeding practices. The CHEW app prototype consisted of WIC Shopping Tools,
      including a barcode scanner and calculator tools for the cash value voucher for
      purchasing fruits and vegetables, and nutrition education focused on healthy
      snacks and beverages, including a Yummy Snack Gallery and Healthy Snacking Tips.
      Mothers of 63 black and Hispanic WIC-participating children ages 2 to 4 years
      tested the CHEW app prototype for 3 months and completed follow-up interviews.
      RESULTS: Study participants testing the app for 3 months used the app on average
      once a week for approximately 4 and a half minutes per session, although
      substantial variation was observed. Usage of specific features averaged at 1 to 2
      times per month for shopping-related activities and 2 to 4 times per month for
      the snack gallery. Mothers classified as users rated the app's WIC Shopping Tools
      relatively high on usability and benefits, although variation in scores and
      qualitative feedback highlighted several barriers that need to be addressed. The
      Yummy Snack Gallery and Healthy Snacking Tips scored higher on usability than
      benefits, suggesting that the nutrition education components may have been
      appealing but too limited in scope and exposure. Qualitative feedback from
      mothers classified as non-users pointed to several important barriers that could
      preclude some WIC participants from using the app at all. CONCLUSIONS: The
      prototype study successfully demonstrated the feasibility of using the CHEW app
      prototype with mothers of WIC-enrolled black and Hispanic preschool-aged
      children, with moderate levels of app usage and moderate to high usability and
      benefits. Future versions with enhanced shopping tools and expanded nutrition
      content should be implemented in WIC clinics to evaluate adoption and behavioral
      outcomes. This study adds to the growing body of research focused on the
      application of technology-based interventions in the WIC program to promote
      program retention and childhood obesity prevention.

PMID- 28768612
TI  - Short-Term Efficacy of an Innovative Mobile Phone Technology-Based Intervention
      for Weight Management for Overweight and Obese Adolescents: Pilot Study.
AB  - BACKGROUND: In the United States, approximately one-third of adolescents are now
      overweight or obese, and one in six is obese. This financial cost and the larger
      nonfinancial costs of obesity make obesity prevention and management for
      adolescents imperative for the health of the nation. However, primary care visits
      are typically brief, and primary care providers may lack adequate resources to
      help overweight or obese adolescents to manage weight issues. To augment the
      efficacy of primary care visits for adolescent weight management, mobile phone
      technology can be used as an adjunct treatment that provides additional
      opportunities for encouraging improvement in lifestyle, attainment, and
      maintenance of healthy weight. OBJECTIVE: The purposes of this study were to (1)
      measure effects of an innovative mobile phone technology-based intervention for
      overweight and obese adolescents and to (2) examine the intervention's
      feasibility for use in primary care clinics. METHODS: The mobile phone-based
      intervention had three components: use of the Fitbit Flex, participation in an
      online educational program, and receipt of biweekly text messages during the
      maintenance phase. A randomized controlled study design was utilized. Data
      regarding anthropometrics (body mass index [BMI] and waist-to-hip ratio), blood
      pressure, levels of physical and sedentary activity, diet, and self-efficacy
      regarding physical activity and diet were collected at baseline and at 3 and 6
      months after the baseline assessment. RESULTS: A total of 40 adolescents
      participated in the study. At the 6-month follow-up visit, compared to
      participants in the control group, the mobile phone-based intervention
      participants had significant improvement in BMI (z=-4.37, P=.001), diastolic
      blood pressure (z=-3.23, P=.001), physical activity days per week (z=2.58,
      P=.01), TV and computer time (z=-3.34, P=.001), servings of fruits and vegetables
      per day (z=2.74, P=.006), servings of soda and sweetened drinks (z=-3.19,
      P=.001), physical activity self-efficacy (z=2.75, P=.006), and dietary self
      efficacy (z=5.05, P=.001). Medium to large effect sizes were found in these
      outcome variables. CONCLUSIONS: The use of mobile technologies may offer a
      practical, reliable adjunct to weight management for overweight and obese
      adolescents in busy primary care clinics serving adolescents. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT 01693250; https://clinicaltrials.gov/ct2/show/NCT01693250?
      term=Adolescent+ obesity+AND+mhealth&rank=5 (Archived by WebCite at ).

PMID- 28768613
TI  - Medicine Goes Female: Protocol for Improving Career Options of Females and
      Working Conditions for Researching Physicians in Clinical Medical Research by
      Organizational Transformation and Participatory Design.
AB  - BACKGROUND: All European countries need to increase the number of health
      professionals in the near future. Most efforts have not brought the expected
      results so far. The current notion is that this is mainly related to the fact
      that female physicians will clearly outnumber their male colleagues within a few
      years in nearly all European countries. Still, women are underrepresented in
      leadership and research positions throughout Europe. OBJECTIVES: The MedGoFem
      project addresses multiple perspectives with the participation of multiple
      stakeholders. The goal is to facilitate the implementation of Gender Equality
      Plans (GEP) in university hospitals; thereby, transforming the working conditions
      for women working as researchers and highly qualified physicians simultaneously.
      Our proposed innovation, a crosscutting topic in all research and clinical
      activities, must become an essential part of university hospital strategic
      concepts. METHODS: We capture the current status with gender-sensitive
      demographic data concerning medical staff and conduct Web-based surveys to
      identify cultural, country-specific, and interdisciplinary factors conducive to
      women's academic success. Individual expectations of employees regarding job
      satisfaction and working conditions will be visualized based on "personal
      construct theory" through repertory grids. An expert board working out scenarios
      and a gender topic agenda will identify culture-, nation-, and discipline
      specific aspects of gender equality. University hospitals in 7 countries will
      establish consensus groups, which work on related topics. Hospital management
      supports the consensus groups, valuates group results, and shares discussion
      results and suggested measures across groups. Central findings of the consensus
      groups will be prepared as exemplary case studies for academic teaching on
      research and work organization, leadership, and management. RESULTS: A discussion
      group on gender equality in academic medicine will be established on an
      internationally renowned open-research platform. Project results will be
      published in peer-reviewed journals with high-impact factors. In addition,
      workshops on gender dimension in research using the principles of Gendered
      Innovation will be held. Support and consulting services for hospitals will be
      introduced in order to develop a European consulting service. CONCLUSIONS: The
      main impact of the project will be the implementation of innovative GEP tailored
      to the needs of university hospitals, which will lead to measurable institutional
      change in gender equality. This will impact the research at university hospitals
      in general, and will improve career prospects of female researchers in
      particular. Simultaneously, the gender dimension in medical research as an
      innovation factor and mandatory topic will be strengthened and integrated in each
      individual university hospital research activity. Research funding organizations
      can use the built knowledge to include mandatory topics for funding applications
      to enforce the use and implementation of GEP in university hospitals.

PMID- 28768614
TI  - Prescribing opioids and psychotropic drugs in pregnancy.

PMID- 28768615
TI  - Jane Anderson: HIV and human rights.

PMID- 28768616
TI  - Unmet need in mental health provision.

PMID- 28768617
TI  - Room for improvement: a randomised controlled trial with nested qualitative
      interviews on space, place and treatment delivery.
AB  - OBJECTIVE: Healthcare-oriented design in hospitals can promote better clinical
      outcomes. Creating optimal facilities may increase treatment effects. We
      investigated the influence of the treatment room on effects of exercise therapy.
      METHODS: In a mixed-method randomised controlled double-blind trial, middle-aged
      individuals reporting knee or hip pain performed 8 weeks of exercise therapy in
      (1) a newly built physically enhanced environment, (2) a standard environment or
      (3) were waitlisted, receiving no intervention. Participants and therapists were
      blind to study aim. Primary outcome was participants' Global Perceived Effect
      (GPE; seven-point Likert scale). Six nested focus group interviews with
      participants (n=25) and individual interviews with therapists (n=2) explored
      experiences of the environments. RESULTS: 42 people exercised in the physically
      enhanced environment, 40 in the standard environment, 21 were waitlisted.
      Contrary to our hypothesis, the treatment response seemed greater in the standard
      environment for GPE (0.98, 95% CI0.5 to 1.4) than for the physically enhanced
      environment (0.37, 95% CI -0.2 to 0.9), between-group difference (0.61, 95% CI 
      0.1 to 1.3) did not reach statistical significance (p=0.07). Waitlist group
      reported no improvement (-0.05 95% CI -0.5 to 0.4). In interviews, participants
      from the standard environment expressed greater social cohesion and feeling at
      home. Qualitative themes identified; reflection, sense of fellowship and
      transition. Secondary patient-reported outcomes and qualitative findings
      supported the primary finding, while improvements in muscle strength and aerobic
      capacity did not differ between exercise groups. CONCLUSION: Results suggest that
      the physical environment contributes to treatment response. Matching patients'
      preferences to treatment rooms may improve patient-reported outcomes. TRIAL
      REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02043613.

PMID- 28768618
TI  - Infographic: bright spots-physical activity investments that work.

PMID- 28768619
TI  - Lessons to be learnt from the study 'Sham surgery versus labral repair or biceps
      tenodesis for type II SLAP lesions of the shoulder: a three-armed randomised
      clinical trial'.

PMID- 28768620
TI  - Sixty seconds on . . . drinking and diabetes.

PMID- 28768621
TI  - Ecchymotic angioedema in paediatric systemic lupus erythematosus.

PMID- 28768623
TI  - The fastener that left its mark.

PMID- 28768622
TI  - Preschool children who are frequent attenders in emergency departments: an
      observational study of associated demographics and clinical characteristics.
AB  - BACKGROUND: Unscheduled visits to emergency departments (ED) have increased in
      the UK in recent years. Children who are repeat attenders are relatively
      understudied. AIMS: To describe the sociodemographic and clinical characteristics
      of preschoolers who attend ED a large District General Hospital. METHOD/STUDY
      DESIGN: Observational study analysing routinely collected ED operational data.
      Children attending four or more visits per year were considered as 'frequent
      attenders'. Poisson regression was used with demographic details (age, sex,
      ethnicity, sociodemographic status) to predict number of attendances seen in the
      year. We further analysed detailed diagnostic characteristics of a random sample
      of 10% of attendees. MAIN FINDINGS: 10 169 patients visited in the 12-month
      period with 16 603 attendances. 655 individuals attended on 3335 occasions. 6.4%
      of this population accounted for 20.1% of total visits. In the 10% sample, there
      were 304 attendances, and 69 (23%) had an underlying chronic long-standing
      illness (CLSI). This group were 2.4 times more likely to be admitted as
      inpatients compared with those without such conditions, median length of stay of
      6.2 hours versus 2.5 hours (p=NS). CONCLUSIONS: Frequent ED attenders fall
      broadly into two distinct clinical groups: those who habitually return with self
      limiting conditions and those with or without exacerbation of underlying CLSI.
      Both groups may be amenable to both additional nursing and other forms of
      community support to enhance self-care and continuity of care. Further research
      is required to increase our understanding of specific individual family and
      health system factors that predict repeat attendance in this age group.

PMID- 28768624
TI  - Pseudoexstrophy: a forme fruste of bladder exstrophy.

PMID- 28768625
TI  - Imaging findings in a case of severe chronic osteomyelitis.

PMID- 28768626
TI  - Pathophysiology of thrombotic thrombocytopenic purpura.
AB  - The discovery of a disintegrin-like and metalloproteinase with thrombospondin
      type 1 motif, member 13 (ADAMTS13) revolutionized our approach to thrombotic
      thrombocytopenic purpura (TTP). Inherited or acquired ADAMTS13 deficiency allows
      the unrestrained growth of microthrombi that are composed of von Willebrand
      factor and platelets, which account for the thrombocytopenia, hemolytic anemia,
      schistocytes, and tissue injury that characterize TTP. Most patients with
      acquired TTP respond to a combination of plasma exchange and rituximab, but some
      die or acquire irreversible neurological deficits before they can respond, and
      relapses can occur unpredictably. However, knowledge of the pathophysiology of
      TTP has inspired new ways to prevent early deaths by targeting autoantibody
      production, replenishing ADAMTS13, and blocking microvascular thrombosis despite
      persistent ADAMTS13 deficiency. In addition, monitoring ADAMTS13 has the
      potential to identify patients who are at risk of relapse in time for preventive
      therapy.

PMID- 28768627
TI  - Genetic risk stratification to reduce inhibitor development in the early
      treatment of hemophilia A: a SIPPET analysis.
AB  - A recent randomized trial, the Survey of Inhibitors in Plasma-Product Exposed
      Toddlers (SIPPET), showed a higher risk of inhibitor development with recombinant
      factor VIII (rFVIII) than plasma-derived concentrates (pdFVIII). We investigated
      whether risk stratification by F8 mutation identifies patients who do not suffer
      this deleterious effect of rFVIII. Among 235 randomized patients with severe
      hemophilia A previously untreated with FVIII concentrate, 197 with null mutations
      were classified as high risk and 38 with non-null mutations were classified as
      low risk. With pdFVIII, no inhibitors occurred in those with low genetic risk,
      whereas high-risk patients had a cumulative incidence of 31%. The risk among low-
      and high-risk patients did not differ much when they were treated with rFVIII
      (43% and 47%, respectively). This implies that patients with low genetic risk
      suffer disproportionate harm when treated with rFVIII (risk increment 43%), as
      also shown by the number needed to harm with rFVIII, which was 6.3 for
      genetically high-risk patients and only 2.3 for low-risk patients. Risk
      stratification by F8 mutation does not identify patients who can be safely
      treated with rFVIII, as relates to immunogenicity. This trial was registered at
      the European Clinical Trials Database (EudraCT) as #2009-011186-88 and at
      www.clinicaltrials.gov as #NCT01064284.

PMID- 28768628
TI  - Risk of neonatal drug withdrawal after intrauterine co-exposure to opioids and
      psychotropic medications: cohort study.
AB  - Objectives To assess the impact of in utero co-exposure to psychotropic
      medications and opioids on the incidence and severity of neonatal drug
      withdrawal.Design Observational cohort study.Setting Nationwide sample of
      pregnancies in publicly insured women in the US, nested in the Medicaid Analytic
      eXtract (2000-10).Participants 201 275 pregnant women with public insurance who
      were exposed to opioids around the time of delivery and their liveborn
      infants.Interventions In utero exposure to psychotropic medications, in
      particular antidepressants, atypical antipsychotics, benzodiazepines, gabapentin,
      and non-benzodiazepine hypnotics (Z drugs), with prescriptions filled within the
      same time window as prescriptions for opioids.Main outcome measure Diagnosis of
      neonatal drug withdrawal in infants exposed in utero to opioids and psychotropic
      medications compared with opioids alone.Results The absolute risk for neonatal
      drug withdrawal ranged from 1.0% in infants exposed in utero to prescription
      opioids alone to 11.4% for those exposed to opioids co-prescribed with
      gabapentin. Among neonates exposed in utero to prescription opioids, the relative
      risk adjusted for propensity score was 1.34 (95% confidence interval 1.22 to
      1.47) with concomitant exposure to antidepressants, 1.49 (1.35 to 1.63) with
      benzodiazepines, 1.61 (1.26 to 2.06) with gabapentin, 1.20 (0.95 to 1.51) with
      antipsychotics, and 1.01 (0.88 to 1.15) with Z drugs. In utero exposure to two or
      more psychotropic medications along with opioids was associated with a twofold
      increased risk of withdrawal (2.05, 1.77 to 2.37). The severity of the withdrawal
      seemed increased in neonates exposed to both opioids and psychotropic medications
      compared with opioids alone.Conclusions During pregnancy, the use of psychotropic
      medications in addition to prescription opioids is common, despite a lack of
      safety data. The current findings suggest that these drugs could further increase
      the risk and severity of neonatal drug withdrawal.

PMID- 28768629
TI  - GRIPP2 reporting checklists: tools to improve reporting of patient and public
      involvement in research.
AB  - Background While the patient and public involvement (PPI) evidence base has
      expanded over the past decade, the quality of reporting within papers is often
      inconsistent, limiting our understanding of how it works, in what context, for
      whom, and why.Objective To develop international consensus on the key items to
      report to enhance the quality, transparency, and consistency of the PPI evidence
      base. To collaboratively involve patients as research partners at all stages in
      the development of GRIPP2.Methods The EQUATOR method for developing reporting
      guidelines was used. The original GRIPP (Guidance for Reporting Involvement of
      Patients and the Public) checklist was revised, based on updated systematic
      review evidence. A three round Delphi survey was used to develop consensus on
      items to be included in the guideline. A subsequent face-to-face meeting produced
      agreement on items not reaching consensus during the Delphi process.Results 143
      participants agreed to participate in round one, with an 86% (123/143) response
      for round two and a 78% (112/143) response for round three. The Delphi survey
      identified the need for long form (LF) and short form (SF) versions. GRIPP2-LF
      includes 34 items on aims, definitions, concepts and theory, methods, stages and
      nature of involvement, context, capture or measurement of impact, outcomes,
      economic assessment, and reflections and is suitable for studies where the main
      focus is PPI. GRIPP2-SF includes five items on aims, methods, results, outcomes,
      and critical perspective and is suitable for studies where PPI is a secondary
      focus.Conclusions GRIPP2-LF and GRIPP2-SF represent the first international
      evidence based, consensus informed guidance for reporting patient and public
      involvement in research. Both versions of GRIPP2 aim to improve the quality,
      transparency, and consistency of the international PPI evidence base, to ensure
      PPI practice is based on the best evidence. In order to encourage its wide
      dissemination this article is freely accessible on The BMJ and Research
      Involvement and Engagement journal websites.

PMID- 28768630
TI  - Back to the future: forget ultrasound and focus on clinical assessment in
      rheumatoid arthritis management.
AB  - Ultrasound (US) unquestionably improves many aspects of rheumatoid arthritis (RA)
      diagnosis and management, but no consensus has been reached regarding the optimal
      US methodology that should be used, and high levels of standardisation have not
      yet been attained. Current evidence from two randomised controlled trials does
      not support the US in directing treatment decisions. A return to the endorsement
      of clinical assessment and the adoption of T2T strategies aiming at ACR/EULAR
      remission still represent the standard of care for RA and should be pursued
      through appropriate educational programmes. Thus, for now, the major application
      of sonography in arthritis should have a focus on diagnostic and especially
      differential diagnostic aspects.

PMID- 28768631
TI  - US doctor is shot dead after refusing to prescribe opioids.

PMID- 28768632
TI  - Cap on legal fees for clinical negligence work does not go far enough, defence
      organisations warn.

PMID- 28768633
TI  - Restoring balance to "best interests" disputes in children.

PMID- 28768634
TI  - Attacks with corrosive substances are increasing in UK.

PMID- 28768635
TI  - Royal college urges return to traditional structures for safer surgical care.

PMID- 28768636
TI  - Should we allow overseas visitors free access to NHS services?

PMID- 28768637
TI  - Pharmacological therapies for opioid induced constipation in adults with cancer.

PMID- 28768638
TI  - Doctor and MPs in Italy are assaulted after vaccination law is passed.

PMID- 28768639
TI  - A cross sectional study of the relationship between the exposure of pregnant
      women to military attacks in 2014 in Gaza and the load of heavy metal
      contaminants in the hair of mothers and newborns.
AB  - OBJECTIVE: Metal contamination of humans in war areas has rarely been
      investigated. Weaponry's heavy metals become environmentally stable war remnants
      and accumulate in living things. They also pose health risks in terms of prenatal
      intake, with potential long term risks for reproductive and children's health. We
      studied the contribution of military attacks to the load of 23 metals in the hair
      of Palestinian women in the Gaza Strip, who were pregnant at the time of the
      military attacks in 2014, and their newborns. We compared the metal load in the
      mothers with values for adult hair from outside the war area (RHS) as the
      reference. We investigated heavy metals trans-passing in utero, and assessed if
      the heavy metal intake could derive from sources unrelated to the war. DESIGN:
      Cross sectional study. PARTICIPANTS AND SETTING: Cross sectional convenience
      sample of 502 mothers delivering in the Gaza Strip and their newborns. MAIN
      OUTCOME MEASURED: Measure of the load of heavy metals in mother and newborn hair
      by inductively coupled plasma-mass spectrometry (ICP-MS). Comparison of metal
      loads with the reference RHS, between groups with different exposures to attacks
      and house/agriculture chemicals, and between mothers and newborns. Data for birth
      registry and for exposures to war and other known risk factors were obtained at
      interview with the mothers. Photographic documentation of damage from military
      attacks was obtained. RESULTS: The whole cross sectional convenience sample had a
      significantly higher load of heavy metals than the reference RHS. Women exposed
      to military attacks had a significantly higher load of heavy metals than those
      not exposed; the load in newborns correlated positively with the mothers' load.
      No significant difference was found between users/non-users of house/agriculture
      chemicals. No other known confounder was identified. CONCLUSIONS: High heavy
      metal loads in mothers, reflected in those of their newborns, were associated
      with exposure to military attacks, posing a risk of immediate and long term
      negative outcomes for pregnancy and child health. Surveillance, biomonitoring and
      further research are recommended. Implications for general and public health are
      discussed.

PMID- 28768640
TI  - Clonal Expansion and Interrelatedness of Distinct B-Lineage Compartments in
      Multiple Myeloma Bone Marrow.
AB  - Multiple myeloma is characterized by the clonal expansion of malignant plasma
      cells in the bone marrow. But the phenotypic diversity and the contribution of
      less predominant B-lineage clones to the biology of this disease have been
      controversial. Here, we asked whether cells bearing the dominant multiple myeloma
      immunoglobulin rearrangement occupy phenotypic compartments other than that of
      plasma cells. To accomplish this, we combined 13-parameter FACS index sorting and
      t-Stochastic Neighbor Embedding (t-SNE) visualization with high-throughput single
      cell immunoglobulin sequencing to track selected B-lineage clones across
      different stages of human B-cell development. As expected, the predominant clones
      preferentially mapped to aberrant plasma cell compartments, albeit phenotypically
      altered from wild type. Interestingly, up to 1.2% of cells of the predominant
      clones colocalized with B-lineage cells of a normal phenotype. In addition, minor
      clones with distinct immunoglobulin sequences were detected in up to 9% of
      sequenced cells, but only 2 out of 12 of these clones showed aberrant immune
      phenotypes. The majority of these minor clones showed intraclonal silent
      nucleotide differences within the CDR3s and varying frequencies of somatic
      mutations in the immunoglobulin genes. Therefore, the phenotypic range of
      multiple myeloma cells in the bone marrow is not confined to aberrant-phenotype
      plasma cells but extends to low frequencies of normal-phenotype B cells, in line
      with the recently reported success of B cell-targeting cellular therapies in some
      patients. The majority of minor clones result from parallel nonmalignant
      expansion. Cancer Immunol Res; 5(9); 744-54. (c)2017 AACR.

PMID- 28768642
TI  - Defining the STATus quo in muscle hypertrophy. Focus on "Overload-mediated
      skeletal muscle hypertrophy is not impaired by loss of myofiber STAT3".

PMID- 28768641
TI  - Acute myotube protein synthesis regulation by IL-6-related cytokines.
AB  - IL-6 and leukemia inhibitory factor (LIF), members of the IL-6 family of
      cytokines, play recognized paradoxical roles in skeletal muscle mass regulation,
      being associated with both growth and atrophy. Overload or muscle contractions
      can induce a transient increase in muscle IL-6 and LIF expression, which has a
      regulatory role in muscle hypertrophy. However, the cellular mechanisms involved
      in this regulation have not been completely identified. The induction of
      mammalian target of rapamycin complex 1 (mTORC1)-dependent myofiber protein
      synthesis is an established regulator of muscle hypertrophy, but the involvement
      of the IL-6 family of cytokines in this process is poorly understood. Therefore,
      we investigated the acute effects of IL-6 and LIF administration on mTORC1
      signaling and protein synthesis in C2C12 myotubes. The role of glycoprotein 130
      (gp130) receptor and downstream signaling pathways, including phosphoinositide 3
      kinase (PI3K)-Akt-mTORC1 and signal transducer and activator of transcription 3
      (STAT3)-suppressor of cytokine signaling 3 (SOCS3), was investigated by
      administration of specific siRNA or pharmaceutical inhibitors. Acute
      administration of IL-6 and LIF induced protein synthesis, which was accompanied
      by STAT3 activation, Akt-mTORC1 activation, and increased SOCS3 expression. This
      induction of protein synthesis was blocked by both gp130 siRNA knockdown and Akt
      inhibition. Interestingly, STAT3 inhibition or Akt downstream mTORC1 signaling
      inhibition did not fully block the IL-6 or LIF induction of protein synthesis.
      SOCS3 siRNA knockdown increased basal protein synthesis and extended the duration
      of the protein synthesis induction by IL-6 and LIF. These results demonstrate
      that either IL-6 or LIF can activate gp130-Akt signaling axis, which induces
      protein synthesis via mTORC1-independent mechanisms in cultured myotubes.
      However, IL-6- or LIF-induced SOCS3 negatively regulates the activation of
      myotube protein synthesis.

PMID- 28768643
TI  - Persistent Hyperglycemia Is Associated With Increased Mortality After
      Intracerebral Hemorrhage.
AB  - BACKGROUND: Hyperglycemia may be associated with worse outcome after
      intracerebral hemorrhage (ICH). We assessed the association of early glycemic
      trajectory on ICH mortality and edema growth. METHODS AND RESULTS: We included
      patients from the Helsinki ICH study with glucose measurements at least once
      between both 0 to 24 and 24 to 72 hours from onset. Hyperglycemia was defined as
      blood glucose >=8 mmol/L (144 mg/dL) based on the local threshold for treatment.
      Glycemic trajectory was defined on maximum values 0 to 24 and 24 to 72 hours
      after ICH: (1) persistent normoglycemia in both epochs; (2) late hyperglycemia
      (only between 24 and 72 hours); (3) early hyperglycemia (only before 24 hours);
      and (4) persistent hyperglycemia in both epochs. Logistic regression with known
      predictors of outcome estimated the association of glycemic trajectory and 6
      month mortality. A generalized linear model assessed the association of glycemic
      trajectory and interpolated 72-hour edema extension distance. A total of 576
      patients met eligibility criteria, of whom 214 (37.2%) had persistent
      normoglycemia, 44 (7.6%) late hyperglycemia, 151 (26.2%) early hyperglycemia, and
      167 (29.0%) persistent hyperglycemia. Six-month mortality was higher in the
      persistent (51.1%) and early (26.3%) hyperglycemia groups than the normoglycemia
      (19.0%) and late hyperglycemia (3.6%) groups. Persistent hyperglycemia was
      associated with 6-month mortality (odds ratio 3.675, 95% CI 1.989-6.792;
      P<0.001). Both univariate (P=0.426) and multivariable (P=0.493) generalized
      linear model analyses showed no association between glycemic trajectory and 72
      hour edema extension distance. CONCLUSION: Early hyperglycemia after ICH is
      harmful if it is persistent. Strategies to achieve glycemic control after ICH may
      influence patient outcome and need to be assessed in clinical trials.

PMID- 28768645
TI  - Utilization of Statins Beyond the Initial Period After Stroke and 1-Year Risk of
      Recurrent Stroke.
AB  - BACKGROUND: In-hospital discontinuation of statins has been linked to poorer
      early stroke outcomes, but the consequences of postdischarge discontinuation or
      dose reduction of statin treatment are unknown. The objective of this study was
      to explore the effects of statin discontinuation or statin dose reduction on
      recurrent stroke risk. METHODS AND RESULTS: We conducted a nationwide cohort
      study using the data from the Taiwan National Health Insurance Research Database.
      Our source population comprised all patients who were prescribed a statin within
      90 days of discharge after an ischemic stroke between 2001 and 2012. Patients
      were categorized into 3 groups: statin-discontinued, statin-reduced, and statin
      maintained. Cox proportional hazard models were used to estimate the hazard
      ratios and 95%CIs of recurrent stroke during 1-year follow-up in the groups who
      discontinued statins or reduced statin dose compared with the group who
      maintained statins as the reference. Among the 45 151 ischemic stroke patients
      meeting criteria, during the day-90 to day-180 period, 7.0% were on reduced
      statin therapy, and 18.5% were not on any statin therapy. Compared with
      maintained-statin intensity therapy, discontinuation of statins was associated
      with an increased hazard of recurrent stroke (adjusted hazard ratio 1.42, 95%CI
      1.28-1.57), whereas reduced-statin dose was not associated with an additional
      risk (adjusted hazard ratio 0.94, 95%CI 0.78-1.12). Propensity-matching analysis
      obtained similar results. CONCLUSIONS: Discontinuation of statin therapy between
      3 and 6 months after an index ischemic stroke was associated with a higher risk
      of recurrent stroke within 1 year after statin discontinuation.

PMID- 28768644
TI  - Age and Sex Disparities in Discharge Statin Prescribing in the Stroke Belt:
      Evidence From the Reasons for Geographic and Racial Differences in Stroke Study.
AB  - BACKGROUND: Stroke is a costly and debilitating disease that disproportionately
      affects blacks. Despite the efficacy of statins, evidence suggests racial
      disparities may exist in statin prescribing. METHODS AND RESULTS: We analyzed
      discharge medications for participants hospitalized for an ischemic stroke during
      follow-up of the REGARDS (Reasons for Geographic and Racial Differences in
      Stroke) study. Medications on admission and discharge were abstracted from
      medical records. Among the 666 eligible incident strokes (2003-2013), analyses
      were restricted to 323 participants who were not statin users at the time of
      admission and had no history of atrial fibrillation. Overall, 48.7% were
      prescribed a statin on discharge. In the Stroke Belt, participants aged 65 years
      and older were 47% less likely to be discharged on a statin compared with those
      younger than 65 years (relative risk [RR], 0.53; 95% CI, 0.38-0.74). This
      association was not observed in non-Stroke Belt residents. Outside the Stroke
      Belt, blacks were more likely than whites to be discharged on a statin (RR, 1.42;
      95% CI, 1.04-1.94), while no black:white association was present among Stroke
      Belt residents (RR, 0.93; 95% CI, 0.69-1.26; P for interaction=0.228). Compared
      with women, men in the Stroke Belt were 31% less likely to be discharged on a
      statin (RR, 0.69; 95% CI, 0.50-0.94) while men outside the Stroke Belt were more
      likely to be discharged on a statin (RR, 1.38; 95% CI, 0.99-1.92; P for
      interaction=0.004). CONCLUSIONS: Statin discharge prescribing may differ among
      Stroke Belt and non-Stroke Belt residents, particularly in older Americans and
      men.

PMID- 28768646
TI  - Inflammatory Bowel Disease and Risk of Ischemic Heart Disease: An Updated Meta
      Analysis of Cohort Studies.
AB  - BACKGROUND: Several immune-mediated diseases have been shown to be associated
      with an increased risk of cardiovascular disease. However, studies evaluating the
      association between inflammatory bowel disease and risk of cardiovascular disease
      reported inconsistent results. We assessed the association between inflammatory
      bowel disease and risk of ischemic heart disease in a meta-analysis of cohort
      studies. METHODS AND RESULTS: We conducted a literature search of PubMed and
      Embase up to October 2016 to identify relevant studies. The summary relative
      risks were calculated using the random-effects models. To explore the source of
      heterogeneity, we performed subgroup and sensitivity analysis. We included 10
      cohort studies that satisfied our inclusion criteria. Patients with inflammatory
      bowel disease were associated with an increased risk of ischemic heart disease
      (relative risk: 1.244; 95% CI, 1.142-1.355). Considerable heterogeneity was
      observed. Crohn's disease showed a significantly increased risk of ischemic heart
      disease (relative risk=1.243; 95% CI, 1.042-1.482) and a positive association was
      also observed in ulcerative colitis (relative risk=1.206; 95% CI, 1.170-1.242).
      CONCLUSIONS: Based on meta-analysis of cohort studies, we found an increased risk
      of ischemic heart disease in patients with inflammatory bowel disease. Large long
      term prospective studies are warranted to confirm our results.

PMID- 28768647
TI  - Activation of Transient Receptor Potential Melastatin Subtype 8 Attenuates Cold
      Induced Hypertension Through Ameliorating Vascular Mitochondrial Dysfunction.
AB  - BACKGROUND: Environmental cold-induced hypertension is common, but how to treat
      cold-induced hypertension remains an obstacle. Transient receptor potential
      melastatin subtype 8 (TRPM8) is a mild cold-sensing nonselective cation channel
      that is activated by menthol. Little is known about the effect of TRPM8
      activation by menthol on mitochondrial Ca2+ homeostasis and the vascular function
      in cold-induced hypertension. METHODS AND RESULTS: Primary vascular smooth muscle
      cells from wild-type or Trpm8-/- mice were cultured. In vitro, we confirmed that
      sarcoplasmic reticulum-resident TRPM8 participated in the regulation of cellular
      and mitochondrial Ca2+ homeostasis in the vascular smooth muscle cells. TRPM8
      activation by menthol antagonized angiotensin II induced mitochondrial
      respiratory dysfunction and excess reactive oxygen species generation by
      preserving pyruvate dehydrogenase activity, which hindered reactive oxygen
      species-triggered Ca2+ influx and the activation of RhoA/Rho kinase pathway. In
      vivo, long-term noxious cold stimulation dramatically increased vasoconstriction
      and blood pressure. The activation of TRPM8 by dietary menthol inhibited vascular
      reactive oxygen species generation, vasoconstriction, and lowered blood pressure
      through attenuating excessive mitochondrial reactive oxygen species mediated the
      activation of RhoA/Rho kinase in a TRPM8-dependent manner. These effects of
      menthol were further validated in angiotensin II-induced hypertensive mice.
      CONCLUSIONS: Long-term dietary menthol treatment targeting and preserving
      mitochondrial function may represent a nonpharmaceutical measure for
      environmental noxious cold-induced hypertension.

PMID- 28768649
TI  - A systematic review and meta-analysis of the effects of isoflavone formulations
      against estrogen-deficient bone resorption in peri- and postmenopausal women.
AB  - Background: Age-related estrogen deficiency leads to accelerated bone resorption.
      There is evidence that, through selective estrogen receptor modulation,
      isoflavones may exert beneficial effects against estrogen-deficient bone loss.
      Isoflavone aglycones show higher bioavailability than their glycosidic
      counterparts and thus may have greater potency.Objective: To summarize evidence,
      we executed a systematic review and meta-analysis examining isoflavone therapies
      and bone mineral density (BMD) loss in peri- and postmenopausal women.Design: We
      systematically searched EMBASE and PubMed for randomized controlled trials (RCTs)
      evaluating isoflavone therapies for treating BMD loss at the lumbar spine and
      femoral neck in estrogen-deficient women. Separate meta-analyses were carried out
      with the use of random-effects models for the lumbar spine and femoral neck for
      all studies providing isoflavones as aglycones.Results: Twenty-six RCTs (n =
      2652) were included in the meta-analysis. At the lumbar spine, isoflavone
      treatment was associated with a significantly (P < 0.00001) higher weighted mean
      difference (WMD) of BMD change of 0.01 (95% CI: 0.01, 0.02) than the control. For
      the femoral neck (18 RCTs, n = 1604), isoflavone treatment showed a significantly
      (P < 0.01) higher WMD of BMD change of 0.01 (95% CI: 0.00, 0.02) compared with
      the control. When isolating studies that provide isoflavone aglycones in their
      treatment arm, the average effect was further significantly increased at the
      spine (5 RCTs, n = 682) to 0.04 (P < 0.00001; 95% CI: 0.02, 0.05) and femoral
      neck (4 RCTs, n = 524) to 0.03 (P < 0.05; 95% CI: 0.00, 0.06) compared with the
      control. This protective effect against bone loss disappeared when only studies
      with formulations comprising predominantly isoflavone glycosides were
      included.Conclusions: Isoflavone treatments exert a moderately beneficial effect
      against estrogen-deficient bone loss in women. The effect appears dependent on
      whether isoflavone treatments are in aglycone form; we conclude that beneficial
      effects against bone loss may be enhanced for isoflavone aglycones.

PMID- 28768648
TI  - C-C Chemokine Receptor Type 5 (CCR5)-Mediated Docking of Transferred Tregs
      Protects Against Early Blood-Brain Barrier Disruption After Stroke.
AB  - BACKGROUND: Despite recent evidence demonstrating a potent protective effect of
      adoptively transferred regulatory T cells (Tregs) in ischemic stroke, the
      mechanism for Treg mobilization and activation in the ischemic brain is,
      remarkably, unknown. This study determines the role of C-C chemokine receptor
      type 5 (CCR5) in mediating the docking and activation of transferred Tregs in
      their protection of early blood-brain barrier disruption after stroke. METHODS
      AND RESULTS: Adoptive transfer of CCR5-/- Tregs failed to reduce brain infarct or
      neurological deficits, indicating an indispensable role of CCR5 in Treg-afforded
      protection against cerebral ischemia. Two-photon live imaging demonstrated that
      CCR5 was critical for Treg docking at the injured vessel wall, where they
      interact with blood-borne neutrophils/macrophages after cerebral ischemic injury.
      CCR5 deficiency on donor Tregs deprived of their early protection against blood
      brain barrier damage. Using flow cytometry, real-time polymerase chain reaction,
      and immunostaining, we confirmed that the expression of CCL5, a CCR5 ligand, was
      significantly elevated on the injured endothelium after cerebral ischemia,
      accompanied by CCR5 upregulation on circulating Tregs. In a Treg-endothelial cell
      coculture, CCR5 expression was induced on Tregs on their exposure to ischemia
      injured endothelial cells. Furthermore, CCR5 induction on Tregs enhanced
      expression of the inhibitory molecule programmed death ligand 1, which in turn
      inhibited neutrophil-derived matrix metallopeptidase 9. CONCLUSIONS: These
      results suggest that CCR5 is a critical molecule for Treg-mediated blood-brain
      barrier protection and a potential target to optimize Treg therapy for stroke.

PMID- 28768650
TI  - Intake of niacin, folate, vitamin B-6, and vitamin B-12 through young adulthood
      and cognitive function in midlife: the Coronary Artery Risk Development in Young
      Adults (CARDIA) study.
AB  - Background: Epidemiologic evidence regarding niacin, folate, vitamin B-6, and
      vitamin B-12 intake in relation to cognitive function is limited, especially in
      midlife.Objective: We hypothesize that higher intake of these B vitamins in young
      adulthood is associated with better cognition later in life.Design: This study
      comprised a community-based multicenter cohort of black and white men and women
      aged 18-30 y in 1985-1986 (year 0, i.e., baseline) from the Coronary Artery Risk
      Development in Young Adults (CARDIA) study (n = 3136). We examined participants'
      CARDIA diet history at years 0, 7, and 20 to assess nutrient intake, including
      dietary and supplemental B vitamins. We measured cognitive function at year 25
      (mean +/- SD age: 50 +/- 4 y) through the use of the Rey Auditory Verbal Learning
      Test (RAVLT) for verbal memory, the Digit Symbol Substitution Test (DSST) for
      psychomotor speed, and a modified Stroop interference test for executive
      function. Higher RAVLT and DSST scores and a lower Stroop score indicated better
      cognitive function. We used multivariable-adjusted linear regressions to estimate
      mean differences in cognitive scores and 95% CIs.Results: Comparing the highest
      quintile with the lowest (quintile 5 compared with quintile 1), cumulative total
      intake of niacin was significantly associated with 3.92 more digits on the DSST
      (95% CI: 2.28, 5.55; P-trend < 0.01) and 1.89 points lower interference score on
      the Stroop test (95% CI: -3.10, -0.68; P-trend = 0.05). Total folate was
      associated with 2.56 more digits on the DSST (95% CI: 0.82, 4.31; P-trend =
      0.01). We also found that higher intakes of vitamin B-6 (quartile 5 compared with
      quartile 1: 2.62; 95% CI: 0.97, 4.28; P-trend = 0.02) and vitamin B-12 (quartile
      5 compared with quartile 1: 2.08; 95% CI: 0.52, 3.65; P-trend = 0.02) resulted in
      better psychomotor speed measured by DSST scores.Conclusion: Higher intake of B
      vitamins throughout young adulthood was associated with better cognitive function
      in midlife.

PMID- 28768651
TI  - Combined bioavailable isoflavones and probiotics improve bone status and estrogen
      metabolism in postmenopausal osteopenic women: a randomized controlled trial.
AB  - Background: Female age-related estrogen deficiency increases the risk of
      osteoporosis, which can be effectively treated with the use of hormone
      replacement therapy. However, hormone replacement therapy is demonstrated to
      increase cancer risk. Bioavailable isoflavones with selective estrogen receptor
      affinity show potential to prevent and treat osteoporosis while minimizing or
      eliminating carcinogenic side effects.Objective: In this study, we sought to
      determine the beneficial effects of a bioavailable isoflavone and probiotic
      treatment against postmenopausal osteopenia.Design: We used a novel red clover
      extract (RCE) rich in isoflavone aglycones and probiotics to concomitantly
      promote uptake and a favorable intestinal bacterial profile to enhance isoflavone
      bioavailability. This was a 12-mo, double-blind, parallel design, placebo
      controlled, randomized controlled trial of 78 postmenopausal osteopenic women
      supplemented with calcium (1200 mg/d), magnesium (550 mg/d), and calcitriol (25
      MUg/d) given either RCE (60 mg isoflavone aglycones/d and probiotics) or a masked
      placebo [control (CON)].Results: RCE significantly attenuated bone mineral
      density (BMD) loss at the L2-L4 lumbar spine vertebra (P < 0.05), femoral neck (P
      < 0.01), and trochanter (P < 0.01) compared with CON (-0.99% and -2.2%; -1.04%
      and -3.05%; and -0.67% and -2.79, respectively). Plasma concentrations of
      collagen type 1 cross-linked C-telopeptide was significantly decreased in the RCE
      group (P < 0.05) compared with CON (-9.40% and -6.76%, respectively). RCE
      significantly elevated the plasma isoflavone concentration (P < 0.05), the
      urinary 2-hydroxyestrone (2-OH) to 16alpha-hydroxyestrone (16alpha-OH) ratio (P <
      0.05), and equol-producer status (P < 0.05) compared with CON. RCE had no
      significant effect on other bone turnover biomarkers. Self-reported diet and
      physical activity were consistent and differences were nonsignificant between
      groups throughout the study. RCE was well tolerated with no adverse
      events.Conclusions: Twice daily RCE intake over 1 y potently attenuated BMD loss
      caused by estrogen deficiency, improved bone turnover, promoted a favorable
      estrogen metabolite profile (2-OH:16alpha-OH), and stimulated equol production in
      postmenopausal women with osteopenia. RCE intake combined with supplementation
      (calcium, magnesium, and calcitriol) was more effective than supplementation
      alone. This trial was registered at clinicaltrials.gov as NCT02174666.

PMID- 28768653
TI  - The dilemma of hyperemesis gravidarum: more answers, and more questions.

PMID- 28768652
TI  - Nut and peanut butter consumption and the risk of esophageal and gastric cancer
      subtypes.
AB  - Background: Nut consumption has been associated with decreased risk of
      colorectal, endometrial, lung, and pancreatic cancers. Polyphenols, fiber,
      vitamins, and minerals in nuts may confer this observed protective effect. To our
      knowledge, no prospective study has evaluated the effect of nut consumption on
      esophageal and gastric cancers.Objective: The objective was to evaluate the
      associations between nut and peanut butter consumption and the risk of esophageal
      and gastric cancers and their different subtypes.Design: In this study we used
      data from the NIH-AARP Diet and Health Study, which enrolled 566,407 persons who
      were 50-71 y old at baseline (1995-1996). The median follow-up time was 15.5 y.
      Intakes of nuts and peanut butter were assessed through the use of a validated
      food-frequency questionnaire. We used Cox proportional hazard models to estimate
      HRs and 95% CIs for esophageal and gastric cancers and their subtypes.Results: We
      identified 966 incident cases of esophageal adenocarcinomas, 323 cases of
      esophageal squamous cell carcinoma, 698 cases of gastric cardia adenocarcinoma,
      and 732 cases of gastric noncardia adenocarcinoma. Compared with those who did
      not consume nuts or peanut butter [lowest category of consumption (C0)],
      participants in the highest category of nut consumption (C3) had a lower risk of
      developing gastric noncardia adenocarcinoma [C3 compared with C0, HR: 0.73 (95%
      CI: 0.57, 0.94)]. This inverse association was also seen for peanut butter
      consumption [C3 compared with C0, HR: 0.75 (95% CI: 0.60, 0.94)]. We observed no
      significant associations between the highest and lowest intakes of nuts or peanut
      butter and the risk of gastric cardia adenocarcinoma, esophageal adenocarcinoma,
      or esophageal squamous cell carcinoma.Conclusions: Among older American adults,
      both nut and peanut butter consumption were inversely associated with the risk of
      gastric noncardia adenocarcinoma. This trial was registered at clinicaltrials.gov
      as NCT00340015.

PMID- 28768654
TI  - Effect of the interaction between diet composition and the PPM1K genetic variant
      on insulin resistance and beta cell function markers during weight loss: results
      from the Nutrient Gene Interactions in Human Obesity: implications for dietary
      guidelines (NUGENOB) randomized trial.
AB  - Background: Circulating branched-chain amino acids (BCAAs) and aromatic amino
      acids (AAAs) have been shown to be associated with insulin resistance and
      diabetes risk. The common rs1440581 T allele in the protein phosphatase Mg2+/Mn2+
      dependent 1K (PPM1K) gene has been related to elevated BCAA concentrations and
      risk of type 2 diabetes.Objective: In the present study, we tested whether
      dietary fat and carbohydrate intakes influenced the association between the
      rs1440581 PPM1K genetic variant and glucose-metabolism traits during weight
      loss.Design: The rs1440581 PPM1K genetic variant was genotyped in a total of 757
      nondiabetic individuals who were randomly assigned to 1 of 2 energy-restricted
      diets that differed in macronutrient composition (low-fat diet: 20-25% fat, 15%
      protein, and 60-65% carbohydrate; high-fat diet: 40-45% fat, 15% protein, and 40
      45% carbohydrate). The changes in fasting glucose, fasting insulin, insulin
      resistance (homeostasis model assessment of insulin resistance) and homeostasis
      model assessment of beta cell function (HOMA-B) were measured after a mean +/- SD
      weight loss of 6.8 +/- 3.4 kg over 10 wk and analyzed according to the presence
      of the T allele of rs1440581.Results: The rs1440581 T allele was associated with
      a smaller improvement in glucose concentrations after the 10-wk dietary
      intervention (beta +/- SE: 0.05 +/- 0.02 mg/dL; P = 0.03). In addition,
      significant gene-diet interactions were shown for the rs1440581 PPM1K genetic
      variant in relation to changes in insulin and HOMA-B (P-interaction = 0.006 and
      0.002, respectively). In response to the high-fat diet, the T allele was
      associated with a higher reduction of insulin (beta +/- SE: -0.77 +/- 0.40
      MUU/mL; P = 0.04) and HOMA-B (beta +/- SE: -13.2 +/- 3.81; P = 0.003). An
      opposite effect was observed in the low-fat diet group, although in this group
      the T allele was marginally (P = 0.10) and not significantly (P = 0.24)
      associated with insulin and HOMA-B, respectively.Conclusion:PPM1K rs1440581 may
      affect changes in glucose metabolism during weight loss, and this effect is
      dependent on dietary fat and carbohydrate intakes. This trial was registered at
      controlled-trials.com as ISRCTN25867281.

PMID- 28768655
TI  - The use of metabolic balance studies in the objective discrimination between
      intestinal insufficiency and intestinal failure.
AB  - Background: In research settings that use metabolic balance studies (MBSs) of
      stable adult patients with short bowel syndrome, intestinal failure (IF) and
      dependence on parenteral support (PS) have been defined objectively as energy
      absorption <84% of calculated basal metabolic rate (BMR), wet weight (WW)
      absorption <23 g . kg body weight-1 . d-1, or both. Objective: This study aimed
      to explore and validate these borderlines in the clinical setting.Design:
      Intestinal absorption was measured from April 2003 to March 2015 in 175
      consecutive patients with intestinal insufficiency (INS) in 96-h MBSs. They had
      not received PS 3 mo before referral.Results: To avoid the need for PS, the
      minimum absorptive requirements were energy absorption of >=81% of BMR and WW
      absorption of >=21 g . kg body weight-1 . d-1, which were equivalent to findings
      in research settings (differences of 3.6% and 8.7%; P = 0.65 and 0.60,
      respectively). Oral failure defined as energy intake <130% of calculated BMR or
      WW intake <40 g . kg body weight-1 . d-1 was seen in 71% and 82% of the 10% of
      patients with the lowest energy absorption and WW absorption,
      respectively.Conclusions: In clinical settings, the borderlines between INS and
      IF were not significantly different from those in research settings, even in an
      unselected patient population in which oral failure was also a predominant cause
      of nutritional dyshomeostasis. MBSs may be recommended to identify the individual
      patient in the spectrum from INS to IF, to objectivize the cause of nutritional
      dyshomeostasis (oral failure, malabsorption, or both), and to quantify the
      effects of treatment.

PMID- 28768656
TI  - Antidepressants and murder: case not closed.

PMID- 28768657
TI  - Energy homeostasis in apolipoprotein AIV and cholecystokinin-deficient mice.
AB  - Apolipoprotein AIV (ApoAIV) and cholecystokinin (CCK) are well-known satiating
      signals that are stimulated by fat consumption. Peripheral ApoAIV and CCK
      interact to prolong satiating signals. In the present study, we hypothesized that
      ApoAIV and CCK control energy homeostasis in response to high-fat diet feeding.
      To test this hypothesis, energy homeostasis in ApoAIV and CCK double knockout
      (ApoAIV/CCK-KO), ApoAIV knockout (ApoAIV-KO), and CCK knockout (CCK-KO) mice were
      monitored. When animals were maintained on a low-fat diet, ApoAIV/CCK-KO, ApoAIV
      KO, and CCK-KO mice had comparable energy intake and expenditure, body weight,
      fat mass, fat absorption, and plasma parameters relative to the controls. In
      contrast, these KO mice exhibited impaired lipid transport to epididymal fat pads
      in response to intraduodenal infusion of dietary lipids. Furthermore, ApoAIV-KO
      mice had upregulated levels of CCK receptor 2 (CCK2R) in the small intestine
      while ApoAIV/CCK-KO mice had upregulated levels of CCK2R in the brown adipose
      tissue. After 20 wk of a high-fat diet, ApoAIV-KO and CCK-KO mice had comparable
      body weight and fat mass, as well as lower energy expenditure at some time
      points. However, ApoAIV/CCK-KO mice exhibited reduced body weight and adiposity
      relative to wild-type mice, despite having normal food intake. Furthermore,
      ApoAIV/CCK-KO mice displayed normal fat absorption and locomotor activity, as
      well as enhanced energy expenditure. These observations suggest that mice lacking
      ApoAIV and CCK have reduced body weight and adiposity, possibly due to impaired
      lipid transport and elevated energy expenditure.

PMID- 28768658
TI  - Detection of maltodextrin and its discrimination from sucrose are independent of
      the T1R2 + T1R3 heterodimer.
AB  - Maltodextrins, such as Maltrin and Polycose, are glucose polymer mixtures of
      varying chain lengths that are palatable to rodents. Although glucose and other
      sugars activate the T1R2 + T1R3 "sweet" taste receptor, recent evidence from T1R2
      or T1R3-knockout (KO) mice suggests that maltodextrins, despite their glucose
      polymer composition, activate a separate receptor mechanism to generate a taste
      percept qualitatively distinguishable from that of sweeteners. However, explicit
      discrimination of maltodextrins from prototypical sweeteners has not yet been
      psychophysically tested in any murine model. Therefore, mice lacking T1R2 + T1R3
      and wild-type controls were tested in a two-response taste discrimination task to
      determine whether maltodextrins are 1) detectable when both receptor subunits are
      absent and 2) perceptually distinct from that of sucrose irrespective of
      viscosity, intensity, and hedonics. Most KO mice displayed similar Polycose
      sensitivity as controls. However, some KO mice were only sensitive to the higher
      Polycose concentrations, implicating potential allelic variation in the putative
      polysaccharide receptor or downstream pathways unmasked by the absence of T1R2 +
      T1R3. Varied Maltrin and sucrose concentrations of approximately matched
      viscosities were then presented to render the oral somatosensory features,
      intensity, and hedonic value of the solutions irrelevant. Although both genotypes
      competently discriminated Maltrin from sucrose, performance was apparently driven
      by the different orosensory percepts of the two stimuli in control mice and the
      presence of a Maltrin but not sucrose orosensory cue in KO mice. These data
      support the proposed presence of an orosensory receptor mechanism that gives rise
      to a qualitatively distinguishable sensation from that of sucrose.

PMID- 28768659
TI  - Elucidating the role of leptin in systemic inflammation: a study targeting
      physiological leptin levels in rats and their macrophages.
AB  - To elucidate the role of leptin in acute systemic inflammation, we investigated
      how its infusion at low, physiologically relevant doses affects the responses to
      bacterial lipopolysaccharide (LPS) in rats subjected to 24 h of food deprivation.
      Leptin was infused subcutaneously (0-20 MUg.kg-1.h-1) or
      intracerebroventricularly (0-1 MUg.kg-1.h-1). Using hypothermia and hypotension
      as biomarkers of systemic inflammation, we identified the phase extending from 90
      to 240 min post-LPS as the most susceptible to modulation by leptin. In this
      phase, leptin suppressed the rise in plasma TNF-alpha and accelerated the
      recoveries from hypothermia and hypotension. Suppression of TNF-alpha was not
      accompanied by changes in other cytokines or prostaglandins. Leptin suppressed
      TNF-alpha when infused peripherally but not when infused into the brain.
      Importantly, the leptin dose that suppressed TNF-alpha corresponded to the lowest
      dose that limited food consumption; this dose elevated plasma leptin within the
      physiological range (to 5.9 ng/ml). We then conducted in vitro experiments to
      investigate whether an action of leptin on macrophages could parallel our in vivo
      observations. The results revealed that, when sensitized by food deprivation, LPS
      stimulated peritoneal macrophages can be inhibited by leptin at concentrations
      that are lower than those reported to promote cytokine release. It is concluded
      that physiological levels of leptin do not exert a proinflammatory effect but
      rather an anti-inflammatory effect involving selective suppression of TNF-alpha
      via an action outside the brain. The mechanism of this effect might involve a
      previously unrecognized, suppressive action of leptin on macrophage
      subpopulations sensitized by food deprivation, but future studies are warranted.

PMID- 28768661
TI  - All-trans-retinoic acid-mediated cytoprotection in LLC-PK1 renal epithelial cells
      is coupled to p-ERK activation in a ROS-independent manner.
AB  - Although all-trans-retinoic acid (ATRA) provides protection against a variety of
      conditions in vivo, particularly ischemia, the molecular mechanisms underpinning
      these effects remain unclear. The present studies were designed to assess
      potential mechanisms by which ATRA affords cytoprotection against renal toxicants
      in LLC-PK1 cells. Pretreatment of LLC-PK1 cells with ATRA (25 MUM) for 24 h
      afforded cytoprotection against oncotic cell death induced by p-aminophenol
      (PAP), 2-(glutathion-S-yl)hydroquinone (MGHQ), and iodoacetamide but not against
      apoptotic cell death induced by cisplatin. Inhibition of protein synthesis with
      cycloheximide blunted ATRA protection, indicating essential cell survival
      pathways must be engaged before toxicant exposure to provide cytoprotection.
      Interestingly, ATRA did not prevent the PAP-induced generation of reactive oxygen
      species (ROS) nor did it alter glutathione levels. Moreover, ATRA had no
      significant effect on Nrf2 protein expression, and the Nrf2 inducers sulforaphane
      and MG132 did not influence ATRA cytoprotection, suggesting cytoprotective
      pathways beyond those that influence ROS levels contribute to ATRA protection. In
      contrast, ATRA rapidly (15 min) induced levels of the cellular stress kinases p
      ERK and p-AKT at concentrations of ATRA (10 and 25 MUM) required for
      cytoprotection. Consistent with a role for p-ERK in ATRA-mediated cytoprotection,
      inhibition of p-ERK with PD98059 reduced the ability of ATRA to afford protection
      against PAP toxicity. Collectively, these data suggest that p-ERK and its
      downstream targets, independent of ROS and antioxidant signaling, are important
      contributors to the cytoprotective effects of ATRA against oncotic cell death.

PMID- 28768660
TI  - Regulation of energy metabolism during social interactions in rainbow trout: a
      role for AMP-activated protein kinase.
AB  - Rainbow trout (Oncorhynchus mykiss) confined in pairs form social hierarchies in
      which subordinate fish typically experience fasting and high circulating cortisol
      levels, resulting in low growth rates. The present study investigated the role of
      AMP-activated protein kinase (AMPK) in mediating metabolic adjustments associated
      with social status in rainbow trout. After 3 days of social interaction, liver
      AMPK activity was significantly higher in subordinate than dominant or sham (fish
      handled in the same fashion as paired fish but held individually) trout. Elevated
      liver AMPK activity in subordinate fish likely reflected a significantly higher
      ratio of phosphorylated AMPK (phospho-AMPK) to total AMPK protein, which was
      accompanied by significantly higher AMPKalpha1 relative mRNA abundance. Liver ATP
      and creatine phosphate concentrations in subordinate fish also were elevated,
      perhaps as a result of AMPK activity. Sham fish that were fasted for 3 days
      exhibited effects parallel to those of subordinate fish, suggesting that low food
      intake was an important trigger of elevated AMPK activity in subordinate fish.
      Effects on white muscle appeared to be influenced by the physical activity
      associated with social interaction. Overall, muscle AMPK activity was
      significantly higher in dominant and subordinate than sham fish. The ratio of
      phospho-AMPK to total AMPK protein in muscle was highest in subordinate fish,
      while muscle AMPKalpha1 relative mRNA abundance was elevated by social dominance.
      Muscle ATP and creatine phosphate concentrations were high in dominant and
      subordinate fish at 6 h of interaction and decreased significantly thereafter.
      Collectively, the findings of the present study support a role for AMPK in
      mediating liver and white muscle metabolic adjustments associated with social
      hierarchy formation in rainbow trout.

PMID- 28768662
TI  - Stimulation of diuresis and natriuresis by renomedullary infusion of a dual
      inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase.
AB  - The renal medulla, considered critical for the regulation of salt and water
      balance and long-term blood pressure control, is enriched in anandamide and two
      of its major metabolizing enzymes, cyclooxygenase-2 (COX-2) and fatty acid amide
      hydrolase (FAAH). Infusion of anandamide (15, 30, and 60 nmol.min-1.kg-1) into
      the renal medulla of C57BL/6J mice stimulated diuresis and salt excretion in a
      COX-2- but not COX-1-dependent manner. To determine whether endogenous
      endocannabinoids in the renal medulla can elicit similar effects, the effects of
      intramedullary isopropyl dodecyl fluorophosphate (IDFP), which inhibits the two
      major endocannabinoid hydrolases, were studied. IDFP treatment increased the
      urine formation rate and sodium excretion in a COX-2- but not COX-1-dependent
      manner. Neither anandamide nor IDFP affected the glomerular filtration rate.
      Neither systemic (0.625 mg.kg-1.30 min-1 iv) nor intramedullary (15 nmol.min-1.kg
      1.30 min-1) IDFP pretreatment before intramedullary anandamide (15-30 nmol.min
      1.kg-1) strictly blocked effects of anandamide, suggesting that hydrolysis of
      anandamide was not necessary for its diuretic effect. Intramedullary IDFP had no
      effect on renal blood flow but stimulated renal medullary blood flow. The effects
      of IDFP on urine flow rate and medullary blood flow were FAAH-dependent as
      demonstrated using FAAH knockout mice. Analysis of mouse urinary PGE2
      concentrations by HPLC-electrospray ionization tandem mass spectrometry showed
      that IDFP treatment decreased urinary PGE2 These data are consistent with a role
      of FAAH and endogenous anandamide acting through a COX-2-dependent metabolite to
      regulate diuresis and salt excretion in the mouse kidney.

PMID- 28768663
TI  - Effects of multiple simulated birth traumas on urethral continence function in
      rats.
AB  - Multiple vaginal parities have been reported to be an important risk factor for
      stress urinary incontinence (SUI). Simulated birth trauma with single vaginal
      distention (VD) has been used to induce the SUI condition in animals; however,
      the effect of multiple simulated birth traumas on the urethral continence
      function has not been well characterized. Therefore, we examined the effects of
      multiple VDs on urethral functions in vivo and the changes in gene expressions of
      several molecules in the urethra using female SD rats, which were divided into
      three groups; sham, VD-1 (single VD), and VD-3 groups (3 times of VDs every 2
      wk). Two weeks after the final VD, leak point pressure (LPP) and urethral
      responses during sneezing were evaluated. Also, changes in mRNA levels of
      urethral molecules were quantified with RT-PCR. The VD-1 group did not show any
      change in LPP with only a tendency of decrease in amplitudes of the urethral
      responses during sneezing (A-URS); however, the VD-3 group showed a significant
      decrease in LPP and urethral responses such as baseline urethral pressure and A
      URS accompanied with SUI episodes during sneezing. Nicotinic receptor subtypes
      and transforming growth factor (TGF)-beta1 were significantly increased in both
      VD-1 and VD-3 groups while TNF receptor (TNFR)-1, IL-6, collagens, and matrix
      metalloproteinases-9 were significantly increased only in the VD-3 group. These
      data indicate that rats with multiple simulated birth traumas exhibit profound
      impairment of the urethral continence function and that these functional changes
      are associated with those in cytokines, extracellular matrix molecules, and
      nicotinic receptor subtypes in the urethra.

PMID- 28768664
TI  - Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet
      obstruction-induced bladder dysfunction.
AB  - Posterior urethral valves are the most common cause of partial bladder outlet
      obstruction (PBOO) in the pediatric population. Pathological changes in the
      bladder developed during PBOO are responsible for long-lasting voiding
      dysfunction in this population despite early surgical interventions. Increasing
      evidence showed PBOO induces an upregulation of hypoxia-inducible factors (HIFs)
      and their transcriptional target genes, and they play a role in
      pathophysiological changes in the obstructed bladders. We hypothesized that
      blocking HIF pathways can prevent PBOO-induced bladder dysfunction. PBOO was
      surgically created by ligation of the bladder neck in male C57BL/6J mice for 2
      wk. PBOO mice received intraperitoneal injection of either saline or 17-DMAG
      (alvespimycin, 3 mg/kg) every 48 h starting from day 1 postsurgery. Sham-operated
      animals received injection of saline on the same schedule as PBOO mice and served
      as controls. The bladders were harvested after 2 wk, and basal activity and
      evoked contractility of the detrusor smooth muscle (DSM) were evaluated in vitro.
      Bladder function was assessed in vivo by void spot assay and cystometry in
      conscious, unrestrained mice. Results indicated the 17-DMAG treatment preserved
      DSM contractility and partially prevented the development of detrusor over
      activity in obstructed bladders. In addition, PBOO caused a significant increase
      in the frequency of micturition, which was significantly reduced by 17-DMAG
      treatment. The 17-DMAG treatment improved urodynamic parameters, including
      increases in the bladder pressure at micturition and nonvoid contractions
      observed in PBOO mice. These results demonstrate that treatment with 17-DMAG, a
      HIF inhibitor, significantly alleviated PBOO-induced bladder pathology in vivo.

PMID- 28768665
TI  - Dopamine reduces cell surface Na+/H+ exchanger-3 protein by decreasing NHE3
      exocytosis and cell membrane recycling.
AB  - The intrarenal autocrine-paracrine dopamine (DA) system mediates a significant
      fraction of the natriuresis in response to a salt load. DA inhibits a number of
      Na+ transporters to effect sodium excretion, including the proximal tubule Na+/H+
      exchanger-3 (NHE3). DA represent a single hormone that regulates NHE3 at multiple
      levels, including translation, degradation, endocytosis, and protein
      phosphorylation. Because cell surface NHE3 protein is determined by the balance
      between exocytotic insertion and endocytotic retrieval, we examined whether DA
      acutely affects the rate of NHE3 exocytosis in a cell culture model. DA inhibited
      NHE3 exocytosis at a dose-dependent manner with a half maximal around 10-6 M. The
      DA effect on NHE3 exocytosis was blocked by inhibition of protein kinase A and by
      brefeldin A, which inhibits endoplasmic reticulum-to-Golgi transport. NHE3
      directly interacts with the epsilon-subunit of coatomer protein based on yeast
      two-hybrid and coimmunoprecipitation. Because NHE3 has been shown to be recycled
      back to the cell membrane after endocytosis, we measured NHE3 recycling using a
      biochemical reinsertion assay and showed that reinsertion of NHE3 back to the
      membrane is also inhibited by DA. In conclusion, among the many mechanisms by
      which DA reduces apical membrane NHE3 and induces proximal tubule natriuresis,
      one additional mechanism is inhibition of exocytotic insertion and reinsertion of
      NHE3 in the apical cell surface.

PMID- 28768666
TI  - OAB without an overactive bladder in the acute prostaglandin E2 rat model.
AB  - Intravesical prostaglandin E2 (PGE2) was previously used to induce overactive
      bladder (OAB) symptoms, as it reduces bladder capacity in rats and causes a
      "strong urgency sensation" in healthy women. However, the mechanism by which this
      occurs is unclear. To clarify how PGE2 reduces bladder capacity, 100 uM PGE2 was
      administered intravesically during open, single-fill cystometry with simultaneous
      measurement of sphincter EMG in the urethane-anesthetized female Wistar rat. PGE2
      was also applied to the urethra or bladder selectively by use of a ligature at
      the bladder neck before (urethra) or during (bladder) closed-outlet, single-fill
      cystometry. Additional tests of urethral perfusion with PGE2 were made. PGE2
      decreased bladder capacity, increased voiding efficiency, and increased sphincter
      EMG during open cystometry compared with saline controls. The number of
      nonvoiding contractions did not change with PGE2; however, bladder compliance
      decreased. During closed-outlet cystometry, PGE2 applied only to the bladder or
      the urethra did not decrease bladder capacity. Urethral infusion of PGE2
      decreased urethral perfusion pressure. Taken together, these results suggest that
      intravesical PGE2 may decrease bladder capacity by targeting afferents in the
      proximal urethra. This may occur through urethral relaxation and decreased
      bladder compliance, both of which may increase activation of proximal urethra
      afferents from distension of the proximal urethra. This hypothesis stands in
      contrast to many hypotheses of urgency that focus on bladder dysfunction as the
      primary cause of OAB symptoms. Targeting the urethra, particularly urethral
      smooth muscle, may be a promising avenue for the design of drugs and devices to
      treat OAB.

PMID- 28768667
TI  - TRPV4 channels contribute to renal myogenic autoregulation in neonatal pigs.
AB  - Myogenic response, a phenomenon in which resistance size arteries and arterioles
      swiftly constrict or dilate in response to an acute elevation or reduction,
      respectively, in intravascular pressure is a key component of renal
      autoregulation mechanisms. Although it is well established that the renal system
      is functionally immature in neonates, mechanisms that regulate neonatal renal
      blood flow (RBF) remain poorly understood. In this study, we investigated the
      hypothesis that members of the transient receptor potential vanilloid (TRPV)
      channels are molecular components of renal myogenic constriction in newborns. We
      show that unlike TRPV1-3, TRPV4 channels are predominantly expressed in neonatal
      pig preglomerular vascular smooth muscle cells (SMCs). Intracellular Ca2+
      concentration ([Ca2+]i) elevation induced by osmotic cell swelling was attenuated
      by TRPV4, L-type Ca2+, and stretch-activated Ca2+ channel blockers but not
      phospholipase A2 inhibitor. Blockade of TRPV4 channels reversed steady-state
      myogenic tone and inhibited pressure-induced membrane depolarization, [Ca2+]i
      elevation, and constriction in distal interlobular arteries. A step increase in
      arterial pressure induced efficient autoregulation of renal cortical perfusion
      and total RBF in anesthetized and mechanically ventilated neonatal pigs.
      Moreover, intrarenal arterial infusion of the TRPV4 channel blockers HC 067047
      and RN 1734 attenuated renal autoregulation in the pigs. These data suggest that
      renal myogenic autoregulation is functional in neonates. Our findings also
      indicate that TRPV4 channels are mechanosensors in neonatal pig preglomerular
      vascular SMCs and contribute to renal myogenic autoregulation.

PMID- 28768670
TI  - Self-medication complicating pseudo membranous conjunctivitis.
AB  - We aim to highlight the prevalence of using local medications for curing eye
      ailments in a rural population and the harmful consequence of resultant disease,
      ranging from something as mild as conjunctivitis to sight-threatening conditions.
      This case report will address one such incidence where in a local village, the
      doctor known as a registered medical practitioner) in the rural community, uses
      local remedies for his conjunctivitis and ends up in a condition where he cannot
      see anything beyond perceiving light. The membrane removal and treatment with
      topical antibiotic cured his infection, restoring complete recovery of vision.
      This incidence inspired the local village doctor to become an eye health
      educator. He was motivated to spread awareness about the ill effects of self
      medication on eye health. He is also determined to bring all blind people and
      others who need eye care from his remote village to our centre.

PMID- 28768668
TI  - A Combination of Recombinant Mycobacterium bovis BCG Strains Expressing
      Pneumococcal Proteins Induces Cellular and Humoral Immune Responses and Protects
      against Pneumococcal Colonization and Sepsis.
AB  - Pneumococcal diseases remain a substantial cause of mortality in young children
      in developing countries. The development of potentially serotype-transcending
      vaccines has been extensively studied; ideally, such a vaccine should include
      antigens that are able to induce protection against colonization (likely mediated
      by interleukin-17A [IL-17A]) and invasive disease (likely mediated by antibody).
      The use of strong adjuvants or alternative delivery systems that are able to
      improve the immunological response of recombinant proteins has been proposed but
      poses potential safety and practical concerns in children. We have previously
      constructed a recombinant Mycobacterium bovis BCG strain expressing a
      pneumococcal surface protein A (PspA)-PdT fusion protein (rBCG PspA-PdT) that was
      able to induce an effective immune response and protection against sepsis in a
      prime-boost strategy. Here, we constructed two new rBCG strains expressing the
      pneumococcal proteins SP 0148 and SP 2108, which confer IL-17A-dependent
      protection against pneumococcal colonization in mouse models. Immunization of
      mice with rBCG 0148 or rBCG 2108 in a prime-boost strategy induced IL-17A and
      gamma interferon (IFN-gamma) production. The combination of these rBCG strains
      with rBCG PspA-PdT (rBCG Mix), followed by a booster dose of the combined
      recombinant proteins (rMix) induced an IL-17A response against SP 0148 and SP
      2108 and a humoral response characterized by increased levels of IgG2c against
      PspA and functional antibodies against pneumolysin. Furthermore, immunization
      with the rBCG Mix prime/rMix booster (rBCG Mix/rMix) provides protection against
      pneumococcal colonization and sepsis. These results suggest the use of combined
      rBCG strains as a potentially serotype-transcending pneumococcal vaccine in a
      prime-boost strategy, which could provide protection against pneumococcal
      colonization and sepsis.

PMID- 28768671
TI  - Paget-Schroetter syndrome complicated by an incidental pulmonary embolism.
AB  - A young man presented with the severe right upper limb swelling following a heavy
      weight lifting that was thought to be caused by a biceps tendon rupture. However,
      subsequent investigations confirmed the diagnosis of Paget-Schroetter syndrome
      that was associated with an incidental pulmonary embolism. The patient underwent
      a successful thrombolysis followed by a surgical thoracic outlet decompression.
      Overall, the patient has made a good recovery.

PMID- 28768669
TI  - Immunogenicity of Nontypeable Haemophilus influenzae Outer Membrane Vesicles and
      Protective Ability in the Chinchilla Model of Otitis Media.
AB  - Outer membrane vesicles (OMVs) produced by Gram-negative bacteria are enriched in
      several outer membrane components, including major and minor outer membrane
      proteins and lipooligosaccharide. We assessed the functional activity of
      nontypeable Haemophilus influenzae (NTHi) OMV-specific antisera and the
      protective ability of NTHi OMVs as vaccine antigens in the chinchilla otitis
      media model. OMVs were purified from three HMW1/HMW2-expressing NTHi strains, two
      of which were also engineered to overexpress Hia proteins. OMV-specific antisera
      raised in guinea pigs were assessed for their ability to mediate killing of
      representative NTHi in an opsonophagocytic assay. The three OMV-specific antisera
      mediated killing of 18 of 65, 24 of 65, and 30 of 65 unrelated HMW1/HMW2
      expressing NTHi strains. Overall, they mediated killing of 39 of 65 HMW1/HMW2
      expressing strains. The two Hia-expressing OMV-specific antisera mediated killing
      of 17 of 25 and 14 of 25 unrelated Hia-expressing NTHi strains. Overall, they
      mediated killing of 20 of 25 Hia-expressing strains. OMVs from prototype NTHi
      strain 12 were used to immunize chinchillas and the course of middle ear
      infection was monitored following intrabullar challenge with the homologous
      strain. All control animals developed culture-positive otitis media, as did two
      of three HMW1/HMW2-immunized animals. All OMV-immunized animals, with or without
      supplemental HMW1/HMW2 immunization, were completely protected against otitis
      media. NTHi OMVs are the first immunogens examined in this model that provided
      complete protection with sterile immunity after NTHi strain 12 challenge. These
      data suggest that NTHi OMVs hold significant potential as components of
      protective NTHi vaccines, possibly in combination with HMW1/HMW2 proteins.

PMID- 28768672
TI  - An illusion of septic shock: acute generalised exanthematous pustulosis with
      multiorgan dysfunction.
AB  - Acute generalised exanthematous pustulosis (AGEP) is a rare cutaneous eruption,
      most often caused by commonly used antibiotics. It is characterised by an acute
      onset of non-follicular sterile pustular rash and erythema within hours or days
      of drug exposure and usually resolves spontaneously within 1-2 weeks once the
      drug is discontinued. Haemodynamic involvement in the form of shock is rare.
      Here, we present a severe case of AGEP, manifesting with systemic involvement and
      haemodynamic instability resulting in shock with multiorgan dysfunction. The
      associated drugs were erythromycin and fluconazole with a possible combined
      effect of these two drugs that resulted in systemic involvement. Our patient
      improved markedly, both haemodynamically and dermatologically, after
      discontinuation of the drugs and with systemic steroid therapy.

PMID- 28768673
TI  - Insidious enemy: downside to prolonged survival in prostate cancer.
AB  - An 83-year-old man, a prostate cancer survivor of 10 years with multiple
      vertebral metastases presented with sudden onset of double vision. On examination
      he was found to have an isolated partial left abducens palsy with no other
      neurological deficits. Despite having microvascular risk factors, given his
      history of prostate cancer, aMRI brain scan was requested to look for a
      neurological cause. The scan revealed a metastatic lesion in the clivus encasing
      the cavernous sinus and carotid artery. He was referred to his oncologist for
      further management, however he opted out of further treatment and succumbed to
      his illness a month later. This case report includes a literature review of cases
      with clivus metastases secondary to prostate cancer. It highlights the importance
      of carefully examining eye movements and having a high index of suspicion for the
      subtlest sign that may suggest brain metastases in elderly patients with prostate
      cancer with prolonged survival.

PMID- 28768674
TI  - Diagnosis of acrodermatitis enteropathica in resource limited settings.
AB  - Acrodermatitis enteropathica (AE) is a rare inherited zinc deficiency that
      usually manifests in infancy within days in cases of bottlefed infants and days
      to weeks after weaning in breastfed infants. It is characterised by diarrhoea,
      dermatitis, alopecia and systemic symptoms. We report a case of acquired
      nutritional AE in a 6-month-old female infant who had diarrhoeal episodes and the
      characteristic dermatitis lesions in the acral and anogenital regions. She
      responded dramatically to oral zinc supplementation.

PMID- 28768675
TI  - Percutaneous valve in valve in the tricuspid position in a patient with Tetralogy
      of Fallot.
AB  - Here, we describe a case of a successful percutaneous insertion of a
      transcatheter 29 mm Edwards Sapien XT valve into a tricuspid valve in a patient
      with repaired tetralogy of fallot.Similar procedures have been performed with the
      Edwards Sapien valve and Melody valves; however, this is the first case described
      in the literature of an Edwards Sapien valve used in a patient with Tetralogy of
      Fallot.With procedural safety being demonstrated, this case illustrates an
      important alternative treatment option for patients with congenital heart
      disease. Although long-term data is required to compare its efficacy with
      surgically replaced valves, percutaneous procedures can serve as a delay to
      surgical valve replacement which over a patients' lifetime with congenital heart
      disease, can minimise the amount of invasive surgeries and potential
      complications.

PMID- 28768676
TI  - Role of metastasectomy and chemotherapy in carcinoma of uterine cervix.
AB  - Squamous cell carcinoma of uterine cervix is potentially a curable disease;
      however, many patients treated with definitive chemoradiotherapy develop distant
      metastases, with few of them having a single metastatic deposit. There are no
      guidelines for the treatment of patients with oligometastatic cervical cancer.We
      present a case of a patient with International Federation of Gynecology and
      Obstetrics (FIGO) Stage IIB squamous cell carcinoma of uterine cervix. She was
      successfully treated with concurrent chemoradiotherapy with definitive intent.
      One year later, she developed a solitary pulmonary nodule for which she underwent
      resection followed by chemotherapy. She is free of any local or distant disease
      at 5 years of regular follow-up.

PMID- 28768677
TI  - Dinosaur tail sign on spinal MRI in a patient with postdural puncture headache.

PMID- 28768678
TI  - A concept map of death-related anxieties in patients with advanced cancer.
AB  - OBJECTIVES: Fear of death and dying is common in patients with advanced cancer,
      but can be difficult to address in clinical conversations. We aimed to show that
      the experience of death anxiety may be deconstructed into a network of specific
      concerns and to provide a map of their interconnections to aid clinical
      exploration. METHODS: We studied a sample of 382 patients with advanced cancer
      recruited from outpatient clinics at the Princess Margaret Cancer Centre,
      Toronto, Canada. Patients completed the 15-item Death and Dying Distress Scale
      (DADDS). We used item ratings to estimate a regularised partial correlation
      network of death and dying-related concerns. We calculated node closeness
      centrality, clustering and global network characteristics. RESULTS: Death-related
      anxieties were highly frequent, each associated with at least moderate distress
      in 22%-55% of patients. Distress about 'Running out of time' was a central
      concern in the network. The network was organised into two areas: one about more
      practical fears concerning the process of dying and another about more
      psychosocial or existential concerns including relational problems, uncertainty
      about the future and missed opportunities. Both areas were yet closely connected
      by bridges which, for example, linked fear of suffering and a prolonged death to
      fear of burdening others. CONCLUSIONS: Patients with advanced cancer may have
      many interconnected death-related fears that can be patterned in individual ways.
      The bridging links between more practical and more psychosocial concerns
      emphasise that the alleviation of death anxiety may require interventions that
      integrate symptom management, advance care planning and psychological treatment
      approaches.

PMID- 28768679
TI  - Supporting family carers in home-based end-of-life care: using participatory
      action research to develop a training programme for support workers and
      volunteers.
AB  - BACKGROUND: Family carers are crucial in enabling dying people to stay at home,
      but are often not prepared for their caring role, receiving little support from
      formal health and social care services. It is increasingly likely that any help
      or support family carers receive will be provided by a third sector organisation
      on either a voluntary basis or by untrained carer support workers. OBJECTIVES: To
      produce a training programme designed to equip carer support workers and
      volunteers with the basic skills and knowledge needed to support family carers.
      PROCESS OF DEVELOPMENT: Participatory action research, a collaborative form of
      working in which those who are affected by an issue take a lead role in the
      research, was used. Bereaved carers acting as research partners, support workers
      and representatives of third sector organisations took an active part in
      designing, developing, piloting and refining the programme in a number of
      interlinked stages. During development, the programme was piloted on four
      occasions and evaluated by 36 trainees and 3 trainers. FINAL TRAINING PROGRAMME:
      The outcome of the project is an innovative, 1-day training programme, offering
      an introduction to supporting family carers who are looking after someone
      approaching the end of life. The use of participatory action research methods
      enabled the development of a programme that addresses support needs identified by
      bereaved carers and training needs identified by carer support workers.The
      finished programme includes all the materials necessary to run a training day for
      support workers and volunteers: facilitator's notes, trainee workbook, slides,
      promotional poster and pre-course reading for trainees. Knowledge of issues
      involved in end-of-life and palliative care is not required, although some
      experience in delivering training is advisable. CONCLUSION: The programme
      evaluated well during development, but further research is required to examine
      the transfer of learning into the workplace.

PMID- 28768680
TI  - Improving specialist palliative care in residential care for older people: a
      checklist to guide practice.
AB  - OBJECTIVES: Palliative care needs rounds are triage meetings that have been
      introduced in residential care for older adults to help identify and prioritise
      care for people most at risk for unplanned dying with inadequately controlled
      symptoms. This study sought to generate an evidence-based checklist in order to
      support specialist palliative care clinicians integrate care in residential
      nursing homes for older people. METHODS: A grounded theory ethnographic study,
      involving non-participant observation and qualitative interviews. The study was
      conducted at four residential facilities for older people in one city.
      Observations and recordings of 15 meetings were made, and complimented by 13
      interviews with staff attending the needs rounds. RESULTS: The palliative care
      needs round checklist is presented, alongside rich description of how needs
      rounds are conducted. Extracts from interviews with needs rounds participants
      illustrate the choice of items within the checklist and their importance in
      supporting the evolution towards efficient and effective high-quality specialist
      palliative care input to the care of older people living in residential care.
      CONCLUSIONS: The checklist can be used to support the integration of specialist
      palliative care into residential care to drive up quality care, provide staff
      with focused case-based education, maximise planning and reduce symptom burden
      for people at end of life.

PMID- 28768681
TI  - Death talk and relief of death-related distress in patients with advanced cancer.
AB  - OBJECTIVES: The circumstances of advanced cancer heighten the need for affected
      individuals to communicate mortality-related concerns, although there may be
      obstacles to such communication. Managing Cancer and Living Meaningfully(CALM) is
      a supportive-expressive therapy designed to address such barriers and to
      facilitate communication of mortality-related concerns in patients and caregivers
      facing advanced disease. This study explores death-related distress in patients
      with advanced cancer and the perceived influence of CALM therapy on overcoming
      barriers to communication of this distress. METHODS: Semistructured interviews
      were conducted with a subset of patients with advanced cancer (n=17)
      participating in a CALM phase III trial at a large urban regional cancer centre.
      Interviews were transcribed, and qualitative data were analysed using thematic
      analysis. RESULTS: Death-related distress was experienced in terms of three key
      themes: diffuse and overwhelming fear, fear of uncertainty and fear of suffering.
      The perceived barriers to communicating such distress were as follows: reluctance
      of loved ones to discuss mortality-related issues and the participantsa?TM own
      reluctance to discuss death-related concerns to protect their loved ones or
      themselves from distress. CALM therapists were perceived to facilitate
      discussions on dying and death in sessions and to support patientsa?TM
      communication of death-related distress with healthcare providers and loved ones.
      CONCLUSIONS: Patients with advanced cancer perceive barriers to effective
      communication of death distress to be related to their own reluctance, as well as
      reluctance of their loved ones to address such fears. CALM therapy may help
      patients with advanced cancer to overcome obstacles to communication and to
      alleviate death-related distress. TRIAL REGISTRATION NUMBER: NCT01506492.

PMID- 28768682
TI  - Quantitative Characterization of Major Hepatic UDP-Glucuronosyltransferase
      Enzymes in Human Liver Microsomes: Comparison of Two Proteomic Methods and
      Correlation with Catalytic Activity.
AB  - Quantitative characterization of UDP-glucuronosyltransferase (UGT) enzymes is
      valuable in glucuronidation reaction phenotyping, predicting metabolic clearance
      and drug-drug interactions using extrapolation exercises based on pharmacokinetic
      modeling. Different quantitative proteomic workflows have been employed to
      quantify UGT enzymes in various systems, with reports indicating large
      variability in expression, which cannot be explained by interindividual
      variability alone. To evaluate the effect of methodological differences on end
      point UGT abundance quantification, eight UGT enzymes were quantified in 24
      matched liver microsomal samples by two laboratories using stable isotope-labeled
      (SIL) peptides or quantitative concatemer (QconCAT) standard, and measurements
      were assessed against catalytic activity in seven enzymes (n = 59). There was
      little agreement between individual abundance levels reported by the two methods;
      only UGT1A1 showed strong correlation [Spearman rank order correlation (Rs) =
      0.73, P < 0.0001; R2 = 0.30; n = 24]. SIL-based abundance measurements correlated
      well with enzyme activities, with correlations ranging from moderate for UGTs
      1A6, 1A9, and 2B15 (Rs = 0.52-0.59, P < 0.0001; R2 = 0.34-0.58; n = 59) to strong
      correlations for UGTs 1A1, 1A3, 1A4, and 2B7 (Rs = 0.79-0.90, P < 0.0001; R2 =
      0.69-0.79). QconCAT-based data revealed generally poor correlation with activity,
      whereas moderate correlations were shown for UGTs 1A1, 1A3, and 2B7. Spurious
      abundance-activity correlations were identified in the cases of UGT1A4/2B4 and
      UGT2B7/2B15, which could be explained by correlations of protein expression
      between these enzymes. Consistent correlation of UGT abundance with catalytic
      activity, demonstrated by the SIL-based dataset, suggests that quantitative
      proteomic data should be validated against catalytic activity whenever possible.
      In addition, metabolic reaction phenotyping exercises should consider spurious
      abundance-activity correlations to avoid misleading conclusions.

PMID- 28768683
TI  - Getting on the Same Page: Opportunities to Improve Parent-Provider Communication.

PMID- 28768684
TI  - Parent-Provider Miscommunications in Hospitalized Children.
AB  - BACKGROUND: Miscommunications lead to medical errors and suboptimal hospital
      experience. Parent-provider miscommunications are understudied. OBJECTIVES: (1)
      Examine characteristics of parent-provider miscommunications about hospitalized
      children, (2) describe associations among parent-provider miscommunications,
      parent-reported errors, and hospital experience, and (3) compare parent and
      attending physician reports of parent-provider miscommunications. METHODS:
      Prospective cohort study of 471 parents of 0- to 17-year-old medical inpatients
      in a pediatric hospital between May 1, 2013 and October 1, 2014. At discharge,
      parents reported parent-provider miscommunication and type (selecting all
      applicable responses), overall experience, and errors during hospitalization.
      During discharge billing, the attending physicians (n = 52) of a subset of
      patients (n = 217) also reported miscommunications, enabling comparison of parent
      and attending physician reports. We used logistic regression to examine
      characteristics of parent-reported miscommunications; McNemar's test to examine
      associations between miscommunications, errors, and top-box (eg, "excellent")
      experience; and generalized estimating equations to compare parent- and attending
      physician-reported miscommunication rates. RESULTS: Parents completed 406 surveys
      (86.2% response rate). 15.3% of parents (n = 62) reported miscommunications.
      Parents of patients with nonpublic insurance (odds ratio: 1.99; 95% confidence
      interval: 1.03-3.85) and longer lengths of stay (odds ratio: 1.12; 95% confidence
      interval: 1.02-1.23) more commonly reported miscommunications. Parents reporting
      miscommunications were 5.3 times more likely to report errors and 78.6% less
      likely to report top-box overall experience (P < .001 for both). Among patients
      with both parent and attending physician surveys, 16.1% (n = 35) of parents and
      3.7% (n = 8) of attending physicians reported miscommunications (P < .001). Both
      parents and attending physicians attributed miscommunications most often to
      family receipt of conflicting information. CONCLUSIONS: Parent-provider
      miscommunications were associated with parent-reported errors and suboptimal
      hospital experience. Parents reported parent-provider miscommunications more
      often than attending physicians did.

PMID- 28768686
TI  - A molecular signature for anastasis, recovery from the brink of apoptotic cell
      death.
AB  - During apoptosis, executioner caspase activity has been considered a point of no
      return. However, recent studies show that cells can survive caspase activation
      following transient apoptotic stimuli, a process called anastasis. To identify a
      molecular signature, we performed whole-transcriptome RNA sequencing of
      untreated, apoptotic, and recovering HeLa cells. We found that anastasis is an
      active, two-stage program. During the early stage, cells transition from growth
      arrested to growing. In the late stage, HeLa cells change from proliferating to
      migratory. Recovering cells also exhibited prolonged elevation of proangiogenic
      factors. Strikingly, some early-recovery mRNAs, including Snail, were elevated
      first during apoptosis, implying that dying cells poise to recover, even while
      under apoptotic stress. Snail was also required for recovery. This study reveals
      similarities in the anastasis genes, pathways, and cell behaviors to those
      activated in wound healing and identifies a repertoire of potential targets for
      therapeutic manipulation.

PMID- 28768685
TI  - Genetic dissection of early endosomal recycling highlights a TORC1-independent
      role for Rag GTPases.
AB  - Endocytosed cell surface membrane proteins rely on recycling pathways for their
      return to the plasma membrane. Although endosome-to-plasma membrane recycling is
      critical for many cellular processes, much of the required machinery is unknown.
      We discovered that yeast has a recycling route from endosomes to the cell surface
      that functions efficiently after inactivation of the sec7-1 allele of Sec7, which
      controls transit through the Golgi. A genetic screen based on an engineered
      synthetic reporter that exclusively follows this pathway revealed that recycling
      was subject to metabolic control through the Rag GTPases Gtr1 and Gtr2, which
      work downstream of the exchange factor Vam6. Gtr1 and Gtr2 control the recycling
      pathway independently of TORC1 regulation through the Gtr1 interactor Ltv1. We
      further show that the early-endosome recycling route and its control though the
      Vam6>Gtr1/Gtr2>Ltv1 pathway plays a physiological role in regulating the
      abundance of amino acid transporters at the cell surface.

PMID- 28768688
TI  - Use of Adjuvant Pharmacotherapy in Type 1 Diabetes: International Comparison of
      49,996 Individuals in the Prospective Diabetes Follow-up and T1D Exchange
      Registries.

PMID- 28768690
TI  - Limited treatment options for molluscum contagiosum.

PMID- 28768687
TI  - HIT'nDRIVE: patient-specific multidriver gene prioritization for precision
      oncology.
AB  - Prioritizing molecular alterations that act as drivers of cancer remains a
      crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a
      computational method that integrates genomic and transcriptomic data to identify
      a set of patient-specific, sequence-altered genes, with sufficient collective
      influence over dysregulated transcripts. HIT'nDRIVE aims to solve the "random
      walk facility location" (RWFL) problem in a gene (or protein) interaction
      network, which differs from the standard facility location problem by its use of
      an alternative distance measure: "multihitting time," the expected length of the
      shortest random walk from any one of the set of sequence-altered genes to an
      expression-altered target gene. When applied to 2200 tumors from four major
      cancer types, HIT'nDRIVE revealed many potentially clinically actionable driver
      genes. We also demonstrated that it is possible to perform accurate phenotype
      prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules
      from gene interaction networks. In addition, we identified a number of breast
      cancer subtype-specific driver modules that are associated with patients'
      survival outcome. Furthermore, HIT'nDRIVE, when applied to a large panel of pan
      cancer cell lines, accurately predicted drug efficacy using the driver genes and
      their seeded gene modules. Overall, HIT'nDRIVE may help clinicians contextualize
      massive multiomics data in therapeutic decision making, enabling widespread
      implementation of precision oncology.

PMID- 28768689
TI  - Accelerating Wright-Fisher Forward Simulations on the Graphics Processing Unit.
AB  - Forward Wright-Fisher simulations are powerful in their ability to model complex
      demography and selection scenarios, but suffer from slow execution on the Central
      Processor Unit (CPU), thus limiting their usefulness. However, the single-locus
      Wright-Fisher forward algorithm is exceedingly parallelizable, with many steps
      that are so-called "embarrassingly parallel," consisting of a vast number of
      individual computations that are all independent of each other and thus capable
      of being performed concurrently. The rise of modern Graphics Processing Units
      (GPUs) and programming languages designed to leverage the inherent parallel
      nature of these processors have allowed researchers to dramatically speed up many
      programs that have such high arithmetic intensity and intrinsic concurrency. The
      presented GPU Optimized Wright-Fisher simulation, or "GO Fish" for short, can be
      used to simulate arbitrary selection and demographic scenarios while running over
      250-fold faster than its serial counterpart on the CPU. Even modest GPU hardware
      can achieve an impressive speedup of over two orders of magnitude. With
      simulations so accelerated, one can not only do quick parametric bootstrapping of
      previously estimated parameters, but also use simulated results to calculate the
      likelihoods and summary statistics of demographic and selection models against
      real polymorphism data, all without restricting the demographic and selection
      scenarios that can be modeled or requiring approximations to the single-locus
      forward algorithm for efficiency. Further, as many of the parallel programming
      techniques used in this simulation can be applied to other computationally
      intensive algorithms important in population genetics, GO Fish serves as an
      exciting template for future research into accelerating computation in evolution.
      GO Fish is part of the Parallel PopGen Package available at:
      http://dl42.github.io/ParallelPopGen/.

PMID- 28768692
TI  - Does doxycycline delay the next COPD exacerbation?

PMID- 28768691
TI  - Finasteride drug safety alert.

PMID- 28768693
TI  - Nystatin dose change - much ado about nothing?

PMID- 28768694
TI  - Delayed antibiotic prescription for lower respiratory tract infections.

PMID- 28768695
TI  - ? Strontium ranelate discontinued.
AB  - ? Strontium ranelate discontinued ? Limited treatment options for molluscum
      contagiosum ? Finasteride drug safety alert ? Does doxycycline delay the next
      COPD exacerbation? ? Support for WHO standards on reporting clinical trial
      results ? Delayed antibiotic prescription for lower respiratory tract infections
      ? Nystatin dose change - much ado about nothing?

PMID- 28768696
TI  - Support for WHO standards on reporting clinical trial results.

PMID- 28768698
TI  - The future: medical advances in MEN1 therapeutic approaches and management
      strategies.
AB  - Multiple endocrine neoplasia type 1 is a rare autosomal inherited disorder
      associated with a high risk for patients to simultaneously develop tumors of the
      parathyroid glands, duodenopancreatic neuroendocrine tumors and tumors of the
      anterior pituitary gland. Early identification of MEN1 in patients enables
      presymptomatic screening of manifestations, which makes timely interventions
      possible with the intention to prevent morbidity and mortality. Causes of death
      nowadays have shifted toward local or metastatic progression of malignant
      neuroendocrine tumors. In early cohorts, complications like peptic ulcers in
      gastrinoma, renal failure in hyperparathyroidism, hypoglycemia and acute
      hypercalcemia were the primary causes of early mortality. Improved medical
      treatments of these complications led to a significantly improved life
      expectancy. The MEN1 landscape is still evolving, considering the finding of
      breast cancer as a new MEN1-related manifestation and ongoing publications on
      follow-up and medical care for patients with MEN1. This review aims at
      summarizing the most recent insights into the follow-up and medical care for
      patients with MEN1 and identifying the gaps for future research.

PMID- 28768699
TI  - Use of a 23-hour emergency department observation unit for the management of
      patients with toxic exposures.
AB  - BACKGROUND: A significant proportion of patients with toxic exposures presenting
      to the ED require admission. However, most will improve within 24 hours, and so
      could potentially be managed in a short-stay observation unit. We describe the
      management and outcomes of these patients in a 23-hour ED observation unit
      (EDOU). METHODS: A retrospective chart review of all patients with toxic
      exposures admitted to the EDOU in Singapore between 1 April 2013 and 31 March
      2015 was performed. Patient demographics, exposure patterns, clinical
      presentation and interventions received were abstracted. The poisoning severity
      score (PSS) was retrospectively determined. Outcomes were length of stay and
      disposition. RESULTS: A total of 286 patients were analysed, of which 78.0% had
      intentional self-poisoning, 12.2% had bites/stings and 9.8% had unintentional or
      occupational toxic exposures. Analgesics (29.4%), sedatives (12.3%) and
      antidepressants (6.8%) were the most common drugs encountered. The majority of
      patients had a mild (68.9%) or moderate (15.4%) PSS, but 4.2% were graded as
      severe. Most patients with deliberate self-poisoning were reviewed by psychiatry
      (88.8%) and social services (74.9%). Most patients (92.0%) were medically cleared
      during their stay in EDOU, including all 12 with a severe PSS. Of these, 200
      (69.9%) were discharged and 63 (22.0%) were transferred directly to a psychiatric
      unit. The median length of stay in the EDOU was 18 hours (IQR 13-23). CONCLUSION:
      Most patients admitted to the EDOU were successfully managed and medically
      cleared within 23 hours, including those with a severe PSS. The EDOU appears to
      be a suitable alternative to inpatient admission for selected patients.

PMID- 28768700
TI  - Randomised clinical simulation designed to evaluate the effect of telemedicine
      using Google Glass on cardiopulmonary resuscitation (CPR).
AB  - AIM: Through a clinical simulation, this study aims to assess the effect of
      telematics support through Google Glass (GG) from an expert physician on
      performance of cardiopulmonary resuscitation (CPR) performed by a group of
      nurses, as compared with a control group of nurses receiving no assistance.
      METHODS: This was a randomised study carried out at the Catholic University of
      Murcia (November 2014-February 2015). Nursing professionals from the Emergency
      Medical Services in Murcia (Spain) were asked to perform in a clinical simulation
      of cardiac arrest. Half of the nurses were randomly chosen to receive coaching
      from physicians through GG, while the other half did not receive any coaching
      (controls). The main outcome of the study expected was successful defibrillation,
      which restores sinus rhythm. RESULTS: Thirty-six nurses were enrolled in each
      study group. Statistically significant differences were found in the percentages
      of successful defibrillation (100% GG vs 78% control; p=0005) and CPR completion
      times: 213.91 s for GG and 250.31 s for control (average difference=36.39 s (95%
      CI 12.03 to 60.75), p=0.004). CONCLUSIONS: Telematics support by an expert
      through GG improves success rates and completion times while performing CPR in
      simulated clinical situations for nurses in simulated scenarios.

PMID- 28768701
TI  - Hb Baden: a rare high affinity haemoglobin variant and its management.
AB  - Haemoglobin Baden is a rare variant haemoglobin which has only recently been
      clinically and functionally characterised. We present the case of a young adult
      male patient who presented with an erythrocytosis but was clinically
      asymptomatic. His mother was also diagnosed retrospectively having presented with
      erythrocytosis being treated with regular venesections. We discuss the management
      plan and potential significance of being a carrier of this rare haemoglobin
      variant.

PMID- 28768697
TI  - Early-onset torsion dystonia: a novel high-throughput yeast genetic screen for
      factors modifying protein levels of torsinADeltaE.
AB  - Dystonia is the third most common movement disorder, but its diagnosis and
      treatment remain challenging. One of the most severe types of dystonia is early
      onset torsion dystonia (EOTD). The best studied and validated EOTD-associated
      mutation, torsinADeltaE, is a deletion of a C-terminal glutamate residue in the
      AAA+ ATPase torsinA. TorsinA appears to be an endoplasmic reticulum (ER)/nuclear
      envelope chaperone with multiple roles in the secretory pathway and in
      determining subcellular architecture. Many functions are disabled in the
      torsinADeltaE variant, and torsinADeltaE is also less stable than wild-type
      torsinA and is a substrate for ER-associated degradation. Nevertheless, the
      molecular factors involved in the biogenesis and degradation of torsinA and
      torsinADeltaE have not been fully explored. To identify conserved cellular
      factors that can alter torsinADeltaE protein levels, we designed a new high
      throughput, automated, genome-wide screen utilizing our validated Saccharomyces
      cerevisiae torsinA expression system. By analyzing the yeast non-essential gene
      deletion collection, we identified 365 deletion strains with altered
      torsinADeltaE steady-state levels. One notable hit was EUG1, which encodes a
      member of the protein disulfide isomerase family (PDIs). PDIs reside in the ER
      and catalyze the formation of disulfide bonds, mediate protein quality control
      and aid in nascent protein folding. We validated the role of select human PDIs in
      torsinA biogenesis in mammalian cells and found that overexpression of PDIs
      reduced the levels of torsinA and torsinADeltaE. Together, our data report the
      first genome-wide screen to identify cellular factors that alter expression
      levels of the EOTD-associated protein torsinADeltaE. More generally, the
      identified hits help in dissecting the cellular machinery involved in folding and
      degrading a torsinA variant, and constitute potential therapeutic factors for
      EOTD. This screen can also be readily adapted to identify factors impacting the
      levels of any protein of interest, considerably expanding the applicability of
      yeast in both basic and applied research.

PMID- 28768702
TI  - Tumour front inflammation and necrosis are independent prognostic predictors in
      high-grade urothelial carcinoma of the bladder.
AB  - AIMS: Inflammation and necrosis have been associated with prognosis in multiple
      epithelial malignancies. Our objective was to evaluate inflammation and necrosis
      in a cohort of patients with high-grade urothelial carcinomas of the bladder to
      determine their association with pathological parameters and their prognostic
      effect on relapse-free and disease-specific survival. METHODS: A retrospective
      cohort that underwent radical cystectomy for urothelial carcinomas (n=235) was
      evaluated for invasive front and central inflammation using the Klintrup-Makinen
      assessment method. Necrosis was scored using a four-point scale. The relationship
      of inflammation and necrosis with stage, nodal status, carcinoma in situ, tumour
      size, margin status and vascular space invasion and the impact on relapse-free
      and disease-specific survival were calculated using appropriate statistical
      tests. RESULTS: On multivariate analysis, invasive front inflammation (p=0.003)
      and necrosis (p=0.000) were independent predictors of relapse-free survival. Both
      invasive front inflammation (p=0.009) and necrosis (p=0.002) again were
      independent predictors of disease-specific survival. For pathological features,
      low invasive front inflammation was associated with lymphovascular space invasion
      (p=0.008), a positive soft tissue margin (p=0.028) and carcinoma in situ
      (p=0.042). Necrosis was statistically associated with tumours >3a?0/00cm in size
      (p=0.013) and carcinoma in situ (p<0.001). CONCLUSIONS: Necrosis and invasive
      front inflammation are additional histological variables with independent
      prognostic relevance in high-grade urothelial carcinoma of the bladder.

PMID- 28768704
TI  - The good side of cholesterol: a requirement for maintenance of intestinal
      integrity.

PMID- 28768703
TI  - Opposite Regulation of Insulin Sensitivity by Dietary Lipid Versus Carbohydrate
      Excess.
AB  - To understand the mechanisms in lipid-induced insulin resistance, a more
      physiological approach is to enhance fatty acid (FA) availability through the
      diet. Nine healthy men ingested two hypercaloric diets (in 75% excess of habitual
      caloric intake) for 3 days, enriched in unsaturated FA (78 energy % [E%] fat)
      (UNSAT) or carbohydrates (80 E% carbohydrate) (CHO) as well as a eucaloric
      control diet (CON). Compared with CON, the UNSAT diet reduced whole-body and leg
      glucose disposal during a hyperinsulinemic-euglycemic clamp, while decreasing
      hepatic glucose production. In muscle, diacylglycerol (DAG) and intramyocellular
      triacylglycerol were increased. The accumulated DAG was sn-1,3 DAG, which is
      known not to activate PKC, and insulin signaling was intact. UNSAT decreased PDH
      E1alpha protein content and increased inhibitory PDH-E1alpha Ser300
      phosphorylation and FA oxidation. CHO increased whole-body and leg insulin
      sensitivity, while increasing hepatic glucose production. After CHO, muscle PDH
      E1alpha Ser300 phosphorylation was decreased, and glucose oxidation increased.
      After UNSAT, but not CHO, muscle glucose-6-phosphate content was 103% higher
      compared with CON during the clamp. Thus, PDH-E1alpha expression and covalent
      regulation, and hence the tricarboxylic acid cycle influx of pyruvate-derived
      acetyl-CoA relative to beta-oxidation-derived acetyl-CoA, are suggested to impact
      on insulin-stimulated glucose uptake. Taken together, the oxidative metabolic
      fluxes of glucose and FA are powerful and opposite regulators of insulin action
      in muscle.

PMID- 28768705
TI  - Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolism in Health and CKD.
AB  - BACKGROUND AND OBJECTIVES: Vitamin D supplements are prescribed to correct low
      circulating concentrations of 25-hydroxyvitamin D. In CKD, vitamin D metabolism
      is complicated by decreased conversion of 25-hydroxyvitamin D to 1,25
      dihydroxyvitamin D by CYP27B1 and possibly decreased conversion of 25
      hydroxyvitamin D to 24,25-dihydroxyvitamin D by CYP24A1. The aim of this study
      was to determine the effects of vitamin D2 supplementation on vitamin D
      metabolism in health and CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      conducted a treatment-only intervention study of 25 individuals with CKD (eGFR<60
      ml/min per 1.73 m2) and 44 individuals without CKD from three academic centers,
      all with screening 25-hydroxyvitamin D <30 ng/ml. Each participant was prescribed
      vitamin D2 (ergocalciferol) 50,000 IU orally twice weekly for 5 weeks. We tested
      whether changes in plasma concentrations of vitamin D metabolites and vitamin D
      metabolic ratios differed by CKD status. Plasma 1,25-dihydroxyvitamin D3-to-25
      hydroxyvitamin D3 ratio and 24,25-dihydroxyvitamin D3-to-25-hydroxyvitamin D3
      ratio were calculated as estimates of CYP27B1 and CYP24A1 function, respectively.
      RESULTS: With treatment, plasma 25-hydroxyvitamin D2 and total 25-hydroxyvitamin
      D concentrations increased similarly for participants with and without CKD. For
      participants without CKD, 1,25-dihydroxyvitamin D2 increased (2.8+/-1.3-32.9+/
      1.4 pg/ml), whereas 1,25-dihydroxyvitamin D3 decreased (45.6+/-1.9-14.6+/-1.9
      pg/ml), resulting in no significant change in total 1,25-dihydroxyvitamin D; 1,25
      dihydroxyvitamin D3-to-25-hydroxyvitamin D3 ratio decreased (3.0+/-0.2-1.7+/-0.2
      pg/ng), and 24,25-dihydroxyvitamin D3-to-25-hydroxyvitamin D3 ratio increased
      (115.7+/-7.8-195.2+/-7.9 pg/ng). Individuals with CKD had lower baseline levels
      and smaller changes in magnitude for 1,25-dihydroxyvitamin D2 (2.1+/-1.6-24.4+/
      1.6 pg/ml; P interaction =0.01), 1,25-dihydroxyvitamin D3-to-25-hydroxyvitamin D3
      ratio (1.8+/-0.2-1.1+/-0.2 pg/ng; P interaction =0.05), and 24,25
      dihydroxyvitamin D3-to-25-hydroxyvitamin D3 ratio (72.0+/-9.1-110.3+/-9.3 pg/ng;
      P interaction <0.001). Fibroblast growth factor-23 and parathyroid hormone were
      not significantly changed in either group. CONCLUSIONS: Vitamin D2
      supplementation decreases conversion of 25-hydroxyvitamin D3 to 1,25
      dihydroxyvitamin D3 and induces vitamin D3 catabolism as evidenced by changes in
      D3 metabolites and vitamin D metabolic ratios. These effects occur without
      significant changes in fibroblast growth factor-23 or parathyroid hormone and are
      blunted in CKD. PODCAST: This article contains a podcast at https://www.asn
      online.org/media/podcast/CJASN/2017_08_02_CJASNPodcast_17_09.mp3.

PMID- 28768706
TI  - The Prevalence of Cancer-Associated Autoantibodies in Patients with Gastric
      Cancer and Progressive Grades of Premalignant Lesions.
AB  - Background: Serum autoantibodies against tumor-associated antigens (TAAs) are
      detectable in early-stage gastric cancer patients; however, the time point during
      cancerogenesis when they appear in circulation is still obscure.Methods: In this
      study, we developed a recombinant antigen microarray and analyzed the prevalence
      of autoantibodies against 102 TAAs in 829 gastric cancer patients and 929 healthy
      controls from Caucasian and Asian populations, as well as 100 patients with
      chronic atrophic gastritis and 775 individuals staged according to different
      grades of intestinal metaplasia.Results: Six antigens, including CTAG1B/CTAG2,
      DDX53, IGF2BP2, TP53, and MAGEA3, were predominantly reacting with sera from
      gastric cancer patients when compared with healthy controls, and the
      seroreactivity was associated with intestinal-type gastric cancer, but not with
      patients' Helicobacter pylori status, grade, age, gender, or stage of gastric
      cancer. We detected gastric cancer-associated seroreactivity in 13% of patients
      with advanced/severe intestinal metaplasia, which was increased in comparison
      with mild/moderate intestinal metaplasia (5.3%) and was comparable with that seen
      in early-stage gastric cancer patients (12%). Moreover, by testing serum samples
      taken 1 to 9 years before the clinical diagnosis of 18 incident gastric cancer
      cases, we detected autoantibody responses against several TAAs-SOX2, MYC, BIRC5,
      IGF2BP1, and MUC1.Conclusions: Our results suggest that humoral immune response
      against TAAs is generated already during premalignant stages.Impact: Based on the
      obtained results, cancer-associated autoantibodies might make a valuable
      contribution to the stratification of high-risk patients with premalignant
      lesions in the stomach through enhancing the positive predictive power of
      existing risk models. Cancer Epidemiol Biomarkers Prev; 26(10); 1564-74. (c)2017
      AACR.

PMID- 28768708
TI  - Identification of compounds that decrease numbers of Mycobacteria in human
      macrophages in the presence of serum amyloid P.
AB  - Mphis are a heterogeneous population of cells and include classically activated
      Mphis (M1) and alternatively activated Mphis (M2). Mphis can change from M1 to M2
      and vice versa in response to environmental stimuli. Serum amyloid P (SAP) is a
      constitutive plasma protein that polarizes Mphis to an M2 phenotype, and part of
      this effect is mediated through FcgammaRI receptors. In an effort to find ways to
      alter Mphis phenotypes, we screened for compounds that can block the SAP
      FcgammaRI interaction. From a screen of 3000 compounds, we found 12 compounds
      that reduced the ability of fluorescently labeled human SAP to bind cells
      expressing human FcgammaRI. Based on cell surface marker expression, 8 of the
      compounds inhibited the effect of SAP on skewing human Mphis to an M2 phenotype
      and in the presence of SAP polarized Mphis to an M1 phenotype. In diseases, such
      as tuberculosis, M1s are more effective at killing bacteria than M2s. SAP
      potentiated the numbers of the mycobacterial strains Mycobacterium smegmatis and
      Mycobacterium tuberculosis in Mphis. When added along with SAP, 2 of the
      compounds reduced intracellular Mycobacterium numbers. Together, these results
      indicate that the blocking of SAP effects on Mphis can skew these cells toward an
      M1 phenotype, and this may be useful in treating diseases, such as tuberculosis.

PMID- 28768711
TI  - How to attribute causality in quality improvement: lessons from epidemiology.

PMID- 28768709
TI  - Co-stimulatory function in primary germinal center responses: CD40 and B7 are
      required on distinct antigen-presenting cells.
AB  - T cell-dependent germinal center (GC) responses require coordinated interactions
      of T cells with two antigen-presenting cell (APC) populations, B cells and
      dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory
      pathways. Contrary to the prevailing paradigm, we found unique cellular
      requirements for B7 and CD40 expression in primary GC responses to vaccine
      immunization with protein antigen and adjuvant: B7 was required on DCs but was
      not required on B cells, whereas CD40 was required on B cells but not on DCs in
      the generation of antigen-specific follicular helper T cells, antigen-specific GC
      B cells, and high-affinity class-switched antibody production. There was, in
      fact, no requirement for coexpression of B7 and CD40 on the same cell in these
      responses. Our findings support a substantially revised model for co-stimulatory
      function in the primary GC response, with crucial and distinct contributions of
      B7- and CD40-dependent pathways expressed by different APC populations and with
      important implications for understanding how to optimize vaccine responses or
      limit autoimmunity.

PMID- 28768710
TI  - Yap/Taz Deletion in Gli+ Cell-Derived Myofibroblasts Attenuates Fibrosis.
AB  - In damaged kidneys, increased extracellular matrix (ECM) and tissue stiffness
      stimulate kidney fibrosis through incompletely characterized molecular
      mechanisms. The transcriptional coactivators yes-associated protein (Yap) and
      transcriptional coactivator with PDZ-binding motif (Taz) function as
      mechanosensors in cancer cells and have been implicated in the regulation of
      myofibroblasts in the kidney. We hypothesized that the development of kidney
      fibrosis depends on Yap-induced activation and proliferation of kidney
      fibroblasts. In mice, Yap expression increased in renal fibroblasts after
      unilateral ureteral obstruction (UUO), in association with worsening of
      interstitial fibrosis. In cultured fibroblasts, inhibition of Yap/Taz signaling
      blocked TGF-beta1-induced fibroblast-to-myofibroblast transformation and ECM
      production, whereas constitutive activation of Yap promoted fibroblast
      transformation and ECM production even in the absence of TGF-beta1. Moreover, in
      the absence of TGF-beta1, fibroblasts seeded on a stiffened ECM transformed into
      myofibroblasts in a process dependent on the activation of Yap. In mice with UUO,
      the Yap inhibitor verteporfin reduced interstitial fibrosis. Furthermore, Gli1+
      cell-specific knockout of Yap/Taz in mice suppressed UUO-induced ECM deposition,
      myofibroblast accumulation, and interstitial fibrosis. In a UUO-release model,
      induction of Gli1+ cell-specific Yap/Taz knockout partially reversed the
      development of interstitial fibrosis. Thus, in the kidney, Yap is a tissue
      mechanosensor that can be activated by ECM and transforms fibroblasts into
      myofibroblasts; the interaction of Yap/Taz and ECM forms a feed-forward loop
      resulting in kidney fibrosis. Identifying mechanisms that interrupt this
      profibrotic cycle could lead to the development of anti-fibrosis therapy.

PMID- 28768712
TI  - Factors influencing the reporting of adverse medical device events: qualitative
      interviews with physicians about higher risk implantable devices.
AB  - BACKGROUND: Postmarket surveillance of medical devices is reliant on physician
      reporting of adverse medical device events (AMDEs). Little is known about factors
      that influence whether and how physicians report AMDEs, an essential step in
      developing behaviour change interventions. This study explored factors that
      influence AMDE reporting. METHODS: Qualitative interviews were conducted with
      physicians who differed by specialties that implant cardiovascular and
      orthopaedic devices prone to AMDEs, geography and years in practice. Participants
      were asked if and how they reported AMDEs, and the influencing factors. Themes
      were identified inductively using constant comparative technique, and reviewed
      and discussed by the research team on four occasions. RESULTS: Twenty-two
      physicians of varying specialty, region, organisation and career stage perceived
      AMDE reporting as unnecessary, not possible or futile due to multiple factors.
      Physicians viewed AMDEs as an expected part of practice that they could manage by
      switching to different devices or developing work-around strategies for
      problematic devices. Physician beliefs and behaviour were reinforced by limited
      healthcare system capacity and industry responsiveness. The healthcare system
      lacked processes and infrastructure to detect, capture, share and act on
      information about AMDEs, and constrained device choice through purchasing
      contracts. The device industry did not respond to reports of AMDEs from
      physicians or improve their products based on such reports. As a result,
      participants said they used devices that were less than ideal for a given
      patient, leading to suboptimal patient outcomes. CONCLUSIONS: There may be little
      point in solely educating or incentivising individual physicians to report AMDEs
      unless environmental conditions are conducive to doing so. Future research should
      explore policies that govern AMDEs and investigate how to design and implement
      postmarket surveillance systems.

PMID- 28768713
TI  - A meta-analysis and review examining a possible role for oxidative stress and
      singlet oxygen in diverse diseases.
AB  - From kinetic data (k, T) we calculated the thermodynamic parameters for various
      processes (nucleation, elongation, fibrillization, etc.) of proteinaceous
      diseases that are related to the beta-amyloid protein (Alzheimer's), to tau
      protein (Alzheimer's, Pick's), to alpha-synuclein (Parkinson's), prion, amylin
      (type II diabetes), and to alpha-crystallin (cataract). Our calculations led to
      DeltaG? values that vary in the range 92.8-127 kJ mol-1 at 310 K. A value of ~10
      30 kJ mol-1 is the activation energy for the diffusion of reactants, depending on
      the reaction and the medium. The energy needed for the excitation of O2 from the
      ground to the first excited state (1Deltag, singlet oxygen) is equal to 92 kJ mol
      1 So, the DeltaG? is equal to the energy needed for the excitation of ground
      state oxygen to the singlet oxygen (1Deltag first excited) state. The similarity
      of the DeltaG? values is an indication that a common mechanism in the above
      disorders may be taking place. We attribute this common mechanism to the (same)
      role of the oxidative stress and specifically of singlet oxygen, (1Deltag), to
      the above-mentioned processes: excitation of ground state oxygen to the singlet
      oxygen, 1Deltag, state (92 kJ mol-1), and reaction of the empty pi* orbital with
      high electron density regions of biomolecules (~10-30 kJ mol-1 for their
      diffusion). The DeltaG? for cases of heat-induced cell killing (cancer) lie also
      in the above range at 310 K. The present paper is a review and meta-analysis of
      literature data referring to neurodegenerative and other disorders.

PMID- 28768714
TI  - Kinetics of CrPV and HCV IRES-mediated eukaryotic translation using single
      molecule fluorescence microscopy.
AB  - Protein synthesis is a complex multistep process involving many factors that need
      to interact in a coordinated manner to properly translate the messenger RNA. As
      translating ribosomes cannot be synchronized over many elongation cycles, single
      molecule studies have been introduced to bring a deeper understanding of
      prokaryotic translation dynamics. Extending this approach to eukaryotic
      translation is very appealing, but initiation and specific labeling of the
      ribosomes are much more complicated. Here, we use a noncanonical translation
      initiation based on internal ribosome entry sites (IRES), and we monitor the
      passage of individual, unmodified mammalian ribosomes at specific fluorescent
      milestones along mRNA. We explore initiation by two types of IRES, the intergenic
      IRES of cricket paralysis virus (CrPV) and the hepatitis C (HCV) IRES, and show
      that they both strongly limit the rate of the first elongation steps compared to
      the following ones, suggesting that those first elongation cycles do not
      correspond to a canonical elongation. This new system opens the possibility of
      studying both IRES-mediated initiation and elongation kinetics of eukaryotic
      translation and will undoubtedly be a valuable tool to investigate the role of
      translation machinery modifications in human diseases.

PMID- 28768716
TI  - Hard lessons: learning from the Charlie Gard case.

PMID- 28768715
TI  - Architecture and dynamics of overlapped RNA regulatory networks.
AB  - A single protein can bind and regulate many mRNAs. Multiple proteins with similar
      specificities often bind and control overlapping sets of mRNAs. Yet little is
      known about the architecture or dynamics of overlapped networks. We focused on
      three proteins with similar structures and related RNA-binding specificities
      Puf3p, Puf4p, and Puf5p of S. cerevisiae Using RNA Tagging, we identified a
      "super-network" comprised of four subnetworks: Puf3p, Puf4p, and Puf5p
      subnetworks, and one controlled by both Puf4p and Puf5p. The architecture of
      individual subnetworks, and thus the super-network, is determined by competition
      among particular PUF proteins to bind mRNAs, their affinities for binding
      elements, and the abundances of the proteins. The super-network responds
      dramatically: The remaining network can either expand or contract. These
      strikingly opposite outcomes are determined by an interplay between the relative
      abundance of the RNAs and proteins, and their affinities for one another. The
      diverse interplay between overlapping RNA-protein networks provides versatile
      opportunities for regulation and evolution.

PMID- 28768707
TI  - Impact of Childhood Malnutrition on Host Defense and Infection.
AB  - The global impact of childhood malnutrition is staggering. The synergism between
      malnutrition and infection contributes substantially to childhood morbidity and
      mortality. Anthropometric indicators of malnutrition are associated with the
      increased risk and severity of infections caused by many pathogens, including
      viruses, bacteria, protozoa, and helminths. Since childhood malnutrition commonly
      involves the inadequate intake of protein and calories, with superimposed
      micronutrient deficiencies, the causal factors involved in impaired host defense
      are usually not defined. This review focuses on literature related to impaired
      host defense and the risk of infection in primary childhood malnutrition.
      Particular attention is given to longitudinal and prospective cohort human
      studies and studies of experimental animal models that address causal,
      mechanistic relationships between malnutrition and host defense. Protein and
      micronutrient deficiencies impact the hematopoietic and lymphoid organs and
      compromise both innate and adaptive immune functions. Malnutrition-related
      changes in intestinal microbiota contribute to growth faltering and dysregulated
      inflammation and immune function. Although substantial progress has been made in
      understanding the malnutrition-infection synergism, critical gaps in our
      understanding remain. We highlight the need for mechanistic studies that can lead
      to targeted interventions to improve host defense and reduce the morbidity and
      mortality of infectious diseases in this vulnerable population.

PMID- 28768719
TI  - The specialized proresolving lipid mediator maresin 1 protects hepatocytes from
      lipotoxic and hypoxia-induced endoplasmic reticulum stress.
AB  - Endoplasmic reticulum (ER) stress and activation of the unfolded protein response
      (UPR) are hallmarks of nonalcoholic fatty liver disease (NAFLD), which is the
      hepatic manifestation of the metabolic syndrome associated with obesity. The
      specialized proresolving lipid mediator maresin 1 (MaR1) preserves tissue
      homeostasis by exerting cytoprotective actions, dampening inflammation, and
      expediting its timely resolution. Here, we explored whether MaR1 protects liver
      cells from lipotoxic and hypoxia-induced ER stress. Mice were rendered obese by
      high-fat diet feeding, and experiments were performed in primary hepatocytes,
      Kupffer cells, and precision-cut liver slices (PCLSs). Palmitate-induced
      lipotoxicity increased ER stress and altered autophagy in hepatocytes, effects
      that were prevented by MaR1. MaR1 protected hepatocytes against lipotoxicity
      induced apoptosis by activating the UPR prosurvival mechanisms and preventing the
      excessive up-regulation of proapoptotic pathways. Protective MaR1 effects were
      also seen in hepatocytes challenged with hypoxia and TNF-alpha-induced cell
      death. High-throughput microRNA (miRNA) sequencing revealed that MaR1 actions
      were associated with specific miRNA signatures targeting both protein folding and
      apoptosis. MaR1 also prevented lipotoxic-triggered ER stress and hypoxia-induced
      inflammation in PCLSs and enhanced Kupffer cell phagocytic capacity. Together,
      these findings describe the ability of MaR1 to oppose ER stress in liver cells
      under conditions frequently encountered in NAFLD.-Rius, B., Duran-Guell, M.,
      Flores-Costa, R., Lopez-Vicario, C., Lopategi, A., Alcaraz-Quiles, J.,
      Casulleras, M., Lozano, J. J., Titos, E., Claria, J. The specialized proresolving
      lipid mediator maresin 1 protects hepatocytes from lipotoxic and hypoxia-induced
      endoplasmic reticulum stress.

PMID- 28768717
TI  - Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for
      dementia.
AB  - Age-associated memory decline is due to variable combinations of genetic and
      environmental risk factors. How these risk factors interact to drive disease
      onset is currently unknown. Here we begin to elucidate the mechanisms by which
      post-traumatic stress disorder (PTSD) at a young age contributes to an increased
      risk to develop dementia at old age. We show that the actin nucleator Formin 2
      (Fmn2) is deregulated in PTSD and in Alzheimer's disease (AD) patients. Young
      mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding
      impairments of synaptic plasticity, while the consolidation of new memories is
      unaffected. However, Fmn2 mutant mice develop accelerated age-associated memory
      decline that is further increased in the presence of additional risk factors and
      is mechanistically linked to a loss of transcriptional homeostasis. In
      conclusion, our data present a new approach to explore the connection between AD
      risk factors across life span and provide mechanistic insight to the processes by
      which neuropsychiatric diseases at a young age affect the risk for developing
      dementia.

PMID- 28768720
TI  - Angiotensin II regulates phosphorylation of actin-associated proteins in human
      podocytes.
AB  - Within the kidney, angiotensin II (AngII) targets different cell types in the
      vasculature, tubuli, and glomeruli. An important part of the renal filtration
      barrier is composed of podocytes with their actin-rich foot processes. In this
      study, we used stable isotope labeling with amino acids in cell culture coupled
      to mass spectrometry to characterize relative changes in the phosphoproteome of
      human podocytes in response to short-term treatment with AngII. In 4 replicates,
      we identified a total of 17,956 peptides that were traceable to 2081 distinct
      proteins. Bioinformatic analyses revealed that among the increasingly
      phosphorylated peptides are predominantly peptides that are related to actin
      filaments, cytoskeleton, lamellipodia, mammalian target of rapamycin, and MAPK
      signaling. Among others, this screening approach highlighted the increased
      phosphorylation of actin-bundling protein, l-plastin (LCP1). AngII-dependent
      phosphorylation of LCP1 in cultured podocytes was mediated by the kinases ERK,
      p90 ribosomal S6 kinase, PKA, or PKC. LCP1 phosphorylation increased filopodia
      formation. In addition, treatment with AngII led to LCP1 redistribution to the
      cell margins, membrane ruffling, and formation of lamellipodia. Our data
      highlight the importance of AngII-triggered actin cytoskeleton-associated signal
      transduction in podocytes.-Schenk, L. K., Moller-Kerutt, A., Klosowski, R.,
      Wolters, D., Schaffner-Reckinger, E., Weide, T., Pavenstadt, H., Vollenbroker, B.
      Angiotensin II regulates phosphorylation of actin-associated proteins in human
      podocytes.

PMID- 28768718
TI  - APP mouse models for Alzheimer's disease preclinical studies.
AB  - Animal models of human diseases that accurately recapitulate clinical pathology
      are indispensable for understanding molecular mechanisms and advancing
      preclinical studies. The Alzheimer's disease (AD) research community has
      historically used first-generation transgenic (Tg) mouse models that overexpress
      proteins linked to familial AD (FAD), mutant amyloid precursor protein (APP), or
      APP and presenilin (PS). These mice exhibit AD pathology, but the overexpression
      paradigm may cause additional phenotypes unrelated to AD Second-generation mouse
      models contain humanized sequences and clinical mutations in the endogenous mouse
      App gene. These mice show Abeta accumulation without phenotypes related to
      overexpression but are not yet a clinical recapitulation of human AD In this
      review, we evaluate different APP mouse models of AD, and review recent studies
      using the second-generation mice. We advise AD researchers to consider the
      comparative strengths and limitations of each model against the scientific and
      therapeutic goal of a prospective preclinical study.

PMID- 28768721
TI  - The glucocorticoid receptor in monocyte-derived macrophages is critical for
      cardiac infarct repair and remodeling.
AB  - Cell- and tissue-specific actions of glucocorticoids are mediated by the
      glucocorticoid receptor. Here, we demonstrate that the glucocorticoid receptor
      (GR) in macrophages is essential for cardiac healing after myocardial infarction.
      Compared with GRflox (wild-type controls), GRLysMCre mice that lacked GR in
      myeloid cells showed increased acute mortality as a result of cardiac rupture.
      Seven days after left coronary artery ligation, GRLysMCre mice exhibited worse
      cardiac function and adverse remodeling associated with impaired scar formation
      and angiogenic response to ischemic injury. Inactivation of GR altered the
      functional differentiation/maturation of monocyte-derived macrophages in the
      infarcted myocardium. Mechanistically, CD45+/CD11b+/Ly6G-/F4/80+ macrophages
      isolated from GRLysMCre infarcts showed deregulation of factors that control
      inflammation, neovascularization, collagen degradation, and scar tissue
      formation. Moreover, we demonstrate that cardiac fibroblasts sorted from the
      ischemic myocardium of GRLysMCre mice compared with cells isolated from injured
      GRflox hearts displayed higher matrix metalloproteinase 2 expression, and we
      provide evidence that the macrophage GR regulates myofibroblast differentiation
      in the infarct microenvironment during the early phase of wound healing. In
      summary, GR signaling in macrophages, playing a crucial role in tissue-repairing
      mechanisms, could be a potential therapeutic target during wound healing after
      ischemic myocardial injury.-Galuppo, P., Vettorazzi, S., Hovelmann, J., Scholz,
      C.-J., Tuckermann, J. P., Bauersachs, J., Fraccarollo, D. The glucocorticoid
      receptor in monocyte-derived macrophages is critical for cardiac infarct repair
      and remodeling.

PMID- 28768722
TI  - Macrophage migration inhibitory factor enhances Pseudomonas aeruginosa biofilm
      formation, potentially contributing to cystic fibrosis pathogenesis.
AB  - Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator
      that we have previously shown to be associated with an aggressive clinical
      phenotype in cystic fibrosis. It possesses unique tautomerase enzymatic activity.
      However, to date, no human-derived substrate has been identified that has the
      capacity to interact with this cytokine's unique tautomerase activity. This led
      us to hypothesize that MIF may have the capacity to interact with external
      substrates. We describe for the first time how Pseudomonas aeruginosa can utilize
      human recombinant MIF (rMIF) to significantly (P < 0.01) enhance its endogenous
      biofilm formation. Our in vivo studies demonstrate that utilizing a small
      molecular-weight inhibitor targeting MIF's tautomerase activity (SCD-19)
      significantly reduces the inflammatory response in a murine pulmonary chronic P.
      aeruginosa model. In addition, we show that in in vitro experiments, pretreatment
      of P. aeruginosa with rMIF is associated with reduced bacterial killing by
      tobramycin. Our novel findings support the concept of an anti-MIF strategy that
      targets this enzymatic activity as a potential future antibacterial therapeutic
      approach.-Tynan, A., Mawhinney, L., Armstrong, M. E., O'Reilly, C., Kennedy, S.,
      Caraher, E., Julicher, K., O'Dwyer, D., Maher, L., Schaffer, K., Fabre, A.,
      McKone, E. F., Leng, L., Bucala, R., Bernhagen, J., Cooke, G., Donnelly, S. C.
      Macrophage migration inhibitory factor enhances Pseudomonas aeruginosa biofilm
      formation, potentially contributing to cystic fibrosis pathogenesis.

PMID- 28768723
TI  - Lamtor1 Is Critically Required for CD4+ T Cell Proliferation and Regulatory T
      Cell Suppressive Function.
AB  - Mechanistic target of rapamycin complex (mTORC)1 integrates intracellular
      sufficiency of nutrients and regulates various cellular functions. Previous
      studies using mice with conditional knockout of mTORC1 component proteins (i.e.,
      mTOR, Raptor, and Rheb) gave conflicting results on the roles of mTORC1 in CD4+ T
      cells. Lamtor1 is the protein that is required for amino acid sensing and
      activation of mTORC1; however, the roles of Lamtor1 in T cells have not been
      investigated. In this article, we show that Lamtor1-deficient CD4+ T cells
      exhibited marked reductions in proliferation, IL-2 production, mTORC1 activity,
      and expression of purine- and lipid-synthesis genes. Polarization of Th17 cells,
      but not Th1 and Th2 cells, diminished following the loss of Lamtor1. Accordingly,
      CD4-Cre-driven Lamtor1-knockout mice exhibited reduced numbers of CD4+ and CD8+ T
      cells at rest, and they were completely resistant to experimental autoimmune
      encephalomyelitis. In contrast, genetic ablation of Lamtor1 in Foxp3+ T cells
      resulted in severe autoimmunity and premature death. Lamtor1-deficient regulatory
      T cells survived ex vivo as long as wild-type regulatory T cells; however, they
      exhibited a marked loss of suppressive function and expression of signature
      molecules, such as CTLA-4. These results indicate that Lamtor1 plays essential
      roles in CD4+ T cells. Our data suggest that Lamtor1 should be considered a novel
      therapeutic target in immune systems.

PMID- 28768725
TI  - Immune Protection by a Cytomegalovirus Vaccine Vector Expressing a Single Low
      Avidity Epitope.
AB  - Experimental CMV-based vaccine vectors expressing a single MHC class I-restricted
      high-avidity epitope provided strong, T cell-dependent protection against viruses
      or tumors. In this study we tested the low-avidity epitope KCSRNRQYL, and show
      that a mouse CMV (MCMV) vector provides complete immune control of recombinant
      vaccinia virus expressing the same epitope if KCSRNRQYL is expressed within the
      immediate-early MCMV gene ie2 The same epitope expressed within the early M45
      gene provided no protection, although MCMV vectors expressing the high-avidity
      epitope SSIEFARL induced protective immunity irrespective of gene expression
      context. Immune protection was matched by Ag-induced, long-term expansion of
      effector memory CD8 T cells, regardless of epitope avidity. We explained this
      pattern by observing regularities in Ag competition, where responses to high
      avidity epitopes outcompeted weaker ones expressed later in the replicative cycle
      of the virus. Conversely, robust and early expression of a low-avidity epitope
      compensated its weak intrinsic antigenicity, resulting in strong and sustained
      immunity and immune protection.

PMID- 28768726
TI  - Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in
      Experimental Sepsis.
AB  - Sepsis is a leading cause of death in the United States, but the mechanisms
      underlying sepsis-induced immune dysregulation remain poorly understood. 2B4
      (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and
      memory CD8+ T cells that has been shown to regulate T cell function in models of
      viral infection and autoimmunity. In this article, we show that 2B4 signaling
      mediates sepsis lymphocyte dysfunction and mortality. 2B4 expression is increased
      on CD4+ T cells in septic animals and human patients at early time points.
      Importantly, genetic loss or pharmacologic inhibition of 2B4 significantly
      increased survival in a murine cecal ligation and puncture model. Further, CD4
      specific conditional knockouts showed that 2B4 functions on CD4+ T cell
      populations in a cell-intrinsic manner and modulates adaptive and innate immune
      responses during sepsis. Our results illuminate a novel role for 2B4 coinhibitory
      signaling on CD4+ T cells in mediating immune dysregulation.

PMID- 28768724
TI  - PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an
      IL-5-Dependent Mechanism.
AB  - B-1 cells produce natural Abs which provide an integral first line of defense
      against pathogens while also performing important homeostatic housekeeping
      functions. In this study, we demonstrate that programmed cell death 1 ligand 2
      (PD-L2) regulates the production of natural Abs against phosphorylcholine (PC).
      Naive PD-L2-deficient (PD-L2-/-) mice produced significantly more PC-reactive IgM
      and IgA. This afforded PD-L2-/- mice with selectively enhanced protection against
      PC-expressing nontypeable Haemophilus influenzae, but not PC-negative nontypeable
      Haemophilus influenzae, relative to wild-type mice. PD-L2-/- mice had
      significantly increased PC-specific CD138+ splenic plasmablasts bearing a B-1a
      phenotype, and produced PC-reactive Abs largely of the T15 Id. Importantly, PC
      reactive B-1 cells expressed PD-L2 and irradiated chimeras demonstrated that B
      cell-intrinsic PD-L2 expression regulated PC-specific Ab production. In addition
      to increased PC-specific IgM, naive PD-L2-/- mice and irradiated chimeras
      reconstituted with PD-L2-/- B cells had significantly higher levels of IL-5, a
      potent stimulator of B-1 cell Ab production. PD-L2 mAb blockade of wild-type B-1
      cells in culture significantly increased CD138 and Blimp1 expression and PC
      specific IgM, but did not affect proliferation. PD-L2 mAb blockade significantly
      increased IL-5+ T cells in culture. Both IL-5 neutralization and STAT5 inhibition
      blunted the effects of PD-L2 mAb blockade on B-1 cells. Thus, B-1 cell-intrinsic
      PD-L2 expression inhibits IL-5 production by T cells and thereby limits natural
      Ab production by B-1 cells. These findings have broad implications for the
      development of therapeutic strategies aimed at altering natural Ab levels
      critical for protection against infectious disease, autoimmunity, allergy,
      cancer, and atherosclerosis.

PMID- 28768727
TI  - Manipulating Glucose Metabolism during Different Stages of Viral Pathogenesis Can
      Have either Detrimental or Beneficial Effects.
AB  - This report deals with physiological changes and their implication following
      ocular infection with HSV. This infection usually results in a blinding
      inflammatory reaction in the cornea, orchestrated mainly by proinflammatory CD4 T
      cells and constrained in severity by regulatory T cells. In the present report,
      we make the unexpected finding that blood glucose levels change significantly
      during the course of infection. Whereas levels remained normal during the early
      phase of infection when the virus was actively replicating in the cornea, they
      increased around 2-fold during the time when inflammatory responses to the virus
      was occurring. We could show that glucose levels influenced the extent of
      induction of the inflammatory T cell subset in vitro that mainly drives lesions,
      but not regulatory T cells. Additionally, if glucose utilization was limited in
      vivo as a consequence of therapy in the inflammatory phase with the drug 2-deoxy
      glucose (2DG), lesions were diminished compared with untreated infected controls.
      In addition, lesions in 2DG-treated animals contained less proinflammatory
      effectors. Glucose metabolism also influenced the acute phase of infection when
      the replicating virus was present in the eye. Thus, therapy with 2DG to limit
      glucose utilization caused mice to become susceptible to the lethal effects of
      HSV infection, with the virus spreading to the brain causing encephalitis. Taken
      together, our results indicate that glucose metabolism changed during the course
      of HSV infection and that modulating glucose levels can influence the outcome of
      infection, being detrimental or beneficial according to the stage of viral
      pathogenesis.

PMID- 28768728
TI  - Extracellular MicroRNAs Induce Potent Innate Immune Responses via TLR7/MyD88
      Dependent Mechanisms.
AB  - Tissue ischemia, such as transient myocardial ischemia, leads to release of
      cellular RNA including microRNA(miRNA) into the circulation and extracellular (ex
      ) space, but the biological function of the ex-RNA is poorly understood. We
      recently reported that cardiac RNA of both human and rodent origins induced
      cytokine production and immune cell activation. However, the identity of the ex
      RNA responsible for the proinflammatory effect remains unclear. In the current
      study, using an miRNA array, we profiled the plasma miRNAs 4 h after transient
      myocardial ischemia (45 min) or sham procedure. Among 38 plasma miRNAs that were
      elevated following ischemia, eight were tested for their ability to induce
      cytokine response in macrophages and cardiomyocytes. We found that six miRNA
      mimics (miR-34a, -122, -133a, -142, -146a, and -208a) induced cytokine production
      in a dose-dependent manner. The effects of miRNAs (miR-133a, -146a, and -208a)
      were diminished by uridine->adenosine mutation and by RNase pretreatment. The
      miRNA-induced cytokine (MIP-2, TNF-alpha, and IL-6) production was abolished in
      cells deficient of TLR7 or MyD88, or by a TLR7 antagonist, but remained the same
      in TLR3- or Trif-deficient cells. In vivo, mice i.p. injected with miR-133a or
      miR-146a had marked peritoneal neutrophil and monocyte migration, which was
      significantly attenuated in TLR7-/- mice. Moreover, locked nucleic acid anti
      miRNA inhibitors of these six miRNAs markedly reduced cardiac RNA-induced
      cytokine production. Taken together, these data demonstrate that ex-miRNA mimics
      (miR-34a, -122, -133a, -142, -146a, and -208a) are potent innate immune
      activators and that the miRNAs most likely induce cytokine production and
      leukocyte migration through TLR7 signaling.

PMID- 28768729
TI  - Evaluation of a Novel Reporter Virus Neutralization Test for Serological
      Diagnosis of Zika and Dengue Virus Infection.
AB  - Currently, the laboratory diagnosis of Zika virus (ZIKV) infection is primarily
      through the detection of ZIKV RNA or antibodies against ZIKV proteins. The
      detection of viral RNA is highly sensitive and specific, but periods of viremia
      and viruria are brief, limiting the utility of ZIKV RNA assays. Instead, most
      ZIKV infections are diagnosed serologically, using an IgM antibody capture enzyme
      linked immunosorbent assay (MAC-ELISA) for screening, followed by a confirmatory
      plaque reduction neutralization test (PRNT). Typical turnaround times vary, due
      to assay incubation periods and a lack of clinical laboratories performing these
      tests. Recently, a novel luciferase-ZIKV- and -dengue virus (DENV)-based
      serological assay, which considerably improves the turnaround times and
      throughput for ZIKV diagnosis, was described. Using the traditional PRNT as a
      reference method, we evaluated the performance characteristics of the reporter
      virus neutralization test (RVNT) with 258 clinical serum specimens. The ZIKV RVNT
      produced primary ZIKV screening and secondary confirmation results in 4 days,
      with 100% reproducibility. As a screening assay, the ZIKV RVNT displayed
      excellent diagnostic accuracy, sensitivity, and specificity of 98.2%, 100%, and
      98.1%, respectively. As a confirmatory assay, the ZIKV RVNT titers displayed
      93.1% agreement with the traditional ZIKV PRNT titers. Overall, the RVNT
      accurately and reliably detects neutralizing antibodies in patient serum
      specimens, with improved turnaround times, and can be used for the serological
      detection of ZIKV infections. Due to the homogeneous 96-well format, the RVNT has
      also significantly improved the assay throughput to allow testing of a large
      number of specimens in a single run.

PMID- 28768730
TI  - Detection of Plasmodium Infection by the illumigene Malaria Assay Compared to
      Reference Microscopy and Real-Time PCR.
AB  - Malaria is one of the leading causes of infectious disease in travelers returning
      from the tropics. The diagnosis of malaria is typically performed by examining
      Giemsa-stained thick and thin peripheral blood smears, which is time consuming,
      labor intensive, and requires high levels of proficiency. Alternatively, loop
      mediated isothermal amplification (LAMP) is a new molecular method, which is
      rapid, sensitive, and requires less capital equipment and technological training.
      We conducted a retrospective study comparing two formats of a commercial LAMP
      assay (Meridian illumigene malaria [M] and malaria Plus [MP]) versus reference
      microscopy on archived blood specimens (n = 140) obtained from unique returning
      travelers suspected of having malaria. Discrepant results were resolved by either
      repeat testing or a laboratory developed ultrasensitive real-time PCR method. On
      initial testing, the Meridian illumigene M and MP kits had sensitivities of 97.3%
      (95% confidence interval [CI], 90.7 to 99.7%) and 100.0% (95.1 to 100.0%) and
      specificities of 93.8% (84.8 to 98.3%) and 91.5% (81.3 to 97.2%), respectively,
      versus reference microscopy. We project a significant cost reduction in low
      prevalence settings where malaria is not endemic with LAMP-based malaria
      screening given the excellent negative predictive value achieved with LAMP.

PMID- 28768731
TI  - Improved Serodiagnostic Performance for Lyme Disease by Use of Two Recombinant
      Proteins in Enzyme-Linked Immunosorbent Assay Compared to Standardized Two-Tier
      Testing.
AB  - The most reliable test method for the serological confirmation of Lyme disease
      (LD) is a 2-tier method recommended by the CDC in 1995. The first-tier test is a
      low-specificity enzyme-linked immunosorbent assay (ELISA), and the second-tier
      tests are higher-specificity IgG and IgM Western blots. This study describes the
      selection of two Borrelia burgdorferi recombinant proteins and evaluation of
      their performance in a simple 1-tier test for the serological confirmation of LD.
      These two proteins were generated from (i) the full-length dbpA gene combined
      with the invariable region 6 of the vlsE gene (DbpA/C6) and (b) the full-length
      ospC gene (OspC). The expressed DbpA/C6 and OspC proteins were useful in
      detecting anti-Borrelia IgG and IgM antibodies, respectively. A blind study was
      conducted on a well-characterized panel of 279 human sera from the CDC, comparing
      ELISAs using these two recombinant antigens with the 2-tier test method. The two
      methods (DbpA/C6-OspC versus 2-tier test) were equivalent in identifying sera
      from negative-control subjects (99% and 100% specificity, respectively) and in
      detecting stage II and III LD patient sera (100% and 100% sensitivity). However,
      the DbpA/C6-OspC ELISA was markedly better (80% versus 63%) than the 2-tier test
      method in detecting anti-Borrelia antibodies in stage I LD patients. The findings
      suggest that these antigens could be used in a simple 1-tier ELISA that is faster
      to perform, easier to interpret, and less expensive than the 2-tier test method
      and which is better at detecting Borrelia-specific antibodies in sera from
      patients with stage I LD.

PMID- 28768732
TI  - Evaluation of a New Commercial Microarray Platform for the Simultaneous Detection
      of beta-Lactamase and mcr-1 and mcr-2 Genes in Enterobacteriaceae.

PMID- 28768733
TI  - Central catalytic domain of BRAP (RNF52) recognizes the types of ubiquitin chains
      and utilizes oligo-ubiquitin for ubiquitylation.
AB  - Really interesting new gene (RING)-finger protein 52 (RNF52), an E3 ubiquitin
      ligase, is found in eukaryotes from yeast to humans. Human RNF52 is known as
      breast cancer type 1 susceptibility protein (BRCA1)-associated protein 2 (BRAP or
      BRAP2). The central catalytic domain of BRAP comprises four subdomains:
      nucleotide-binding alpha/beta plait (NBP), really interesting new gene (RING)
      zinc finger, ubiquitin-specific protease (UBP)-like zinc finger (ZfUBP), and
      coiled-coil (CC). This domain architecture is conserved in RNF52 orthologs;
      however, the domain's function in the ubiquitin system has not been delineated.
      In the present study, we discovered that the RNF52 domain, comprising NBP-RING
      ZfUBP-CC, binds to ubiquitin chains (oligo-ubiquitin) but not to the ubiquitin
      monomers, and can utilize various ubiquitin chains for ubiquitylation and auto
      ubiquitylation. The RNF52 domain preferentially bound to M1- and K63-linked di
      ubiquitin chains, weakly to K27-linked chains, but not to K6-, K11-, or K48
      linked chains. The binding preferences of the RNF52 domain for ubiquitin-linkage
      types corresponded to ubiquitin usage in the ubiquitylation reaction, except for
      K11-, K29-, and K33-linked chains. Additionally, the RNF52 domain directly
      ligated the intact M1-linked, tri-, and tetra-ubiquitin chains and recognized the
      structural alterations caused by the phosphomimetic mutation of these ubiquitin
      chains. Full-length BRAP had nearly the same specificity for the ubiquitin-chain
      types as the RNF52 domain alone. Mass spectrometry analysis of oligomeric
      ubiquitylation products, mediated by the RNF52 domain, revealed that the
      ubiquitin-linkage types and auto-ubiquitylation sites depend on the length of
      ubiquitin chains. Here, we propose a model for the oligomeric ubiquitylation
      process, controlled by the RNF52 domain, which is not a sequential assembly
      process involving monomers.

PMID- 28768734
TI  - Human tissue models in cancer research: looking beyond the mouse.
AB  - Mouse models, including patient-derived xenograft mice, are widely used to
      address questions in cancer research. However, there are documented flaws in
      these models that can result in the misrepresentation of human tumour biology and
      limit the suitability of the model for translational research. A coordinated
      effort to promote the more widespread development and use of 'non-animal human
      tissue' models could provide a clinically relevant platform for many cancer
      studies, maximising the opportunities presented by human tissue resources such as
      biobanks. A number of key factors limit the wide adoption of non-animal human
      tissue models in cancer research, including deficiencies in the infrastructure
      and the technical tools required to collect, transport, store and maintain human
      tissue for lab use. Another obstacle is the long-standing cultural reliance on
      animal models, which can make researchers resistant to change, often because of
      concerns about historical data compatibility and losing ground in a competitive
      environment while new approaches are embedded in lab practice. There are a wide
      range of initiatives that aim to address these issues by facilitating data
      sharing and promoting collaborations between organisations and researchers who
      work with human tissue. The importance of coordinating biobanks and introducing
      quality standards is gaining momentum. There is an exciting opportunity to
      transform cancer drug discovery by optimising the use of human tissue and
      reducing the reliance on potentially less predictive animal models.

PMID- 28768735
TI  - Therapeutic strategies for spinal muscular atrophy: SMN and beyond.
AB  - Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder
      characterized by loss of motor neurons and muscle atrophy, generally presenting
      in childhood. SMA is caused by low levels of the survival motor neuron protein
      (SMN) due to inactivating mutations in the encoding gene SMN1 A second duplicated
      gene, SMN2, produces very little but sufficient functional protein for survival.
      Therapeutic strategies to increase SMN are in clinical trials, and the first SMN2
      directed antisense oligonucleotide (ASO) therapy has recently been licensed.
      However, several factors suggest that complementary strategies may be needed for
      the long-term maintenance of neuromuscular and other functions in SMA patients.
      Pre-clinical SMA models demonstrate that the requirement for SMN protein is
      highest when the structural connections of the neuromuscular system are being
      established, from late fetal life throughout infancy. Augmenting SMN may not
      address the slow neurodegenerative process underlying progressive functional
      decline beyond childhood in less severe types of SMA. Furthermore, individuals
      receiving SMN-based treatments may be vulnerable to delayed symptoms if rescue of
      the neuromuscular system is incomplete. Finally, a large number of older patients
      living with SMA do not fulfill the present criteria for inclusion in gene therapy
      and ASO clinical trials, and may not benefit from SMN-inducing treatments.
      Therefore, a comprehensive whole-lifespan approach to SMA therapy is required
      that includes both SMN-dependent and SMN-independent strategies that treat the
      CNS and periphery. Here, we review the range of non-SMN pathways implicated in
      SMA pathophysiology and discuss how various model systems can serve as valuable
      tools for SMA drug discovery.

PMID- 28768737
TI  - Intercepting virtual balls approaching under different gravity conditions:
      evidence for spatial prediction.
AB  - To accurately time motor responses when intercepting falling balls we rely on an
      internal model of gravity. However, whether and how such a model is also used to
      estimate the spatial location of interception is still an open question. Here we
      addressed this issue by asking 25 participants to intercept balls projected from
      a fixed location 6 m in front of them and approaching along trajectories with
      different arrival locations, flight durations, and gravity accelerations (0g and
      1g). The trajectories were displayed in an immersive virtual reality system with
      a wide field of view. Participants intercepted approaching balls with a racket,
      and they were free to choose the time and place of interception. We found that
      participants often achieved a better performance with 1g than 0g balls. Moreover,
      the interception points were distributed along the direction of a 1g path for
      both 1g and 0g balls. In the latter case, interceptions tended to cluster on the
      upper half of the racket, indicating that participants aimed at a lower position
      than the actual 0g path. These results suggest that an internal model of gravity
      was probably used in predicting the interception locations. However, we found
      that the difference in performance between 1g and 0g balls was modulated by
      flight duration, the difference being larger for faster balls. In addition, the
      number of peaks in the hand speed profiles increased with flight duration,
      suggesting that visual information was used to adjust the motor response,
      correcting the prediction to some extent.NEW & NOTEWORTHY Here we show that an
      internal model of gravity plays a key role in predicting where to intercept a
      fast-moving target. Participants also assumed an accelerated motion when
      intercepting balls approaching in a virtual environment at constant velocity. We
      also show that the role of visual information in guiding interceptive movement
      increases when more time is available.

PMID- 28768738
TI  - Altered tactile sensitivity in children with attention-deficit hyperactivity
      disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) is characterized by an inability
      to concentrate, heightened activity, and hypermotoric behavior, but sensory
      (e.g., tactile) problems are common. The literature on tactile impairments in
      ADHD is limited, with most work employing clinical observations or
      questionnaires. We studied tactile processing in children with ADHD and
      hypothesized that children with ADHD would show reduced performance in tasks
      closely linked to inhibition. Sixty-seven children with ADHD and 62 typically
      developing children (TDC) performed a battery of tasks grouped in domains: simple
      and choice reaction time; static and dynamic detection threshold (probing
      feedforward inhibition); amplitude discrimination without adaptation and with
      dual and single-site adaptation (probing lateral inhibition and adaptation);
      sequential and simultaneous frequency discrimination (previously linked to GABA);
      and temporal order judgment with and without a synchronous carrier stimulus.
      Children with ADHD could discriminate different amplitudes without adaptation,
      suggesting lateral inhibition is intact, but were negatively affected in all
      adaptation conditions, whereas TDC were only affected during single-site
      adaptation. Children with ADHD also showed normal frequency discrimination.
      Children with ADHD showed slower reaction times and higher detection threshold,
      likely driven by IQ and inattention, because reaction time and detection
      thresholds correlated with IQ and subtle motor signs. Children with ADHD showed a
      pattern of altered tactile processing on specific tasks, suggesting that higher
      cognitive function and cortical mechanisms related to adaptation are affected in
      ADHD, but no clear conclusion can be drawn toward impaired inhibition.NEW &
      NOTEWORTHY This manuscript presents the first tactile psychophysical study
      testing different aspects of tactile processing in attention-deficit
      hyperactivity disorder (ADHD), using large cohort sizes of 67 children with ADHD
      and 65 Typically Developing Children. This study demonstrates impaired tactile
      processing in children with ADHD, on some, but not all tasks (showing this is not
      just due to attention), related to impaired cortical mechanisms. Furthermore,
      both IQ and soft motor skill abnormalities (common in ADHD) are correlated with
      tactile abnormalities.

PMID- 28768739
TI  - A latent low-dimensional common input drives a pool of motor neurons: a
      probabilistic latent state-space model.
AB  - Motor neurons appear to be activated with a common input signal that modulates
      the discharge activity of all neurons in the motor nucleus. It has proven
      difficult for neurophysiologists to quantify the variability in a common input
      signal, but characterization of such a signal may improve our understanding of
      how the activation signal varies across motor tasks. Contemporary methods of
      quantifying the common input to motor neurons rely on compiling discrete action
      potentials into continuous time series, assuming the motor pool acts as a linear
      filter, and requiring signals to be of sufficient duration for frequency
      analysis. We introduce a space-state model in which the discharge activity of
      motor neurons is modeled as inhomogeneous Poisson processes and propose a method
      to quantify an abstract latent trajectory that represents the common input
      received by motor neurons. The approach also approximates the variation in
      synaptic noise in the common input signal. The model is validated with four data
      sets: a simulation of 120 motor units, a pair of integrate-and-fire neurons with
      a Renshaw cell providing inhibitory feedback, the discharge activity of 10
      integrate-and-fire neurons, and the discharge times of concurrently active motor
      units during an isometric voluntary contraction. The simulations revealed that a
      latent state-space model is able to quantify the trajectory and variability of
      the common input signal across all four conditions. When compared with the
      cumulative spike train method of characterizing common input, the state-space
      approach was more sensitive to the details of the common input current and was
      less influenced by the duration of the signal. The state-space approach appears
      to be capable of detecting rather modest changes in common input signals across
      conditions.NEW & NOTEWORTHY We propose a state-space model that explicitly
      delineates a common input signal sent to motor neurons and the physiological
      noise inherent in synaptic signal transmission. This is the first application of
      a deterministic state-space model to represent the discharge characteristics of
      motor units during voluntary contractions.

PMID- 28768740
TI  - Mechanisms for shaping receptive field in monkey area TE.
AB  - Visual object information is conveyed from V1 to area TE along the ventral visual
      pathway with increasing receptive field (RF) sizes. The RFs of TE neurons are
      known to be large, but it is largely unknown how large RFs are shaped along the
      ventral visual pathway. In this study, we addressed this question in two aspects,
      static and dynamic mechanisms, by recording neural responses from macaque area TE
      and V4 to object stimuli presented at various locations in the visual field. As a
      component related to static mechanisms, we found that in area TE, but not in V4,
      response latency to objects presented at fovea were different from objects in
      periphery. As a component of the dynamic mechanisms, we examined effects of
      spatial attention on the RFs of TE neurons. Spatial attention did not affect
      response latency but modulated response magnitudes depending on attended
      location, shifting of the longitudinal axis of RFs toward the attended locations.
      In standard models of large RF formation, downstream neurons pool information
      from nearby RFs, and this process is repeated across the visual field and at each
      step along the ventral visual pathway. The present study revealed that this
      mechanism is not that simple: 1) different circuit mechanisms for foveal and
      peripheral visual fields may be situated between V4 and area TE, and 2) spatial
      attention dynamically changes the shape of RFs.NEW & NOTEWORTHY Receptive fields
      (RFs) of neurons are progressively increased along the ventral visual pathway so
      that an RF at the final stage, area TE, covers a large area of the visual field.
      We explored the mechanism and suggested involvement of parallel circuit
      mechanisms between V4 and TE for foveal and peripheral parts of visual field. We
      also found a dynamic component of RF shape formation through attentional
      modulation of responses in a location-dependent manner.

PMID- 28768736
TI  - Congenital diaphragmatic hernias: from genes to mechanisms to therapies.
AB  - Congenital diaphragmatic hernias (CDHs) and structural anomalies of the diaphragm
      are a common class of congenital birth defects that are associated with
      significant morbidity and mortality due to associated pulmonary hypoplasia,
      pulmonary hypertension and heart failure. In ~30% of CDH patients, genomic
      analyses have identified a range of genetic defects, including chromosomal
      anomalies, copy number variants and sequence variants. The affected genes
      identified in CDH patients include transcription factors, such as GATA4, ZFPM2,
      NR2F2 and WT1, and signaling pathway components, including members of the
      retinoic acid pathway. Mutations in these genes affect diaphragm development and
      can have pleiotropic effects on pulmonary and cardiac development. New therapies,
      including fetal endoscopic tracheal occlusion and prenatal transplacental fetal
      treatments, aim to normalize lung development and pulmonary vascular tone to
      prevent and treat lung hypoplasia and pulmonary hypertension, respectively.
      Studies of the association between particular genetic mutations and clinical
      outcomes should allow us to better understand the origin of this birth defect and
      to improve our ability to predict and identify patients most likely to benefit
      from specialized treatment strategies.

PMID- 28768742
TI  - Multiple spatial representations interact to increase reach accuracy when
      coordinating a saccade with a reach.
AB  - Reaching is an essential behavior that allows primates to interact with the
      environment. Precise reaching to visual targets depends on our ability to
      localize and foveate the target. Despite this, how the saccade system contributes
      to improvements in reach accuracy remains poorly understood. To assess spatial
      contributions of eye movements to reach accuracy, we performed a series of
      behavioral psychophysics experiments in nonhuman primates (Macaca mulatta). We
      found that a coordinated saccade with a reach to a remembered target location
      increases reach accuracy without target foveation. The improvement in reach
      accuracy was similar to that obtained when the subject had visual information
      about the location of the current target in the visual periphery and executed the
      reach while maintaining central fixation. Moreover, we found that the increase in
      reach accuracy elicited by a coordinated movement involved a spatial coupling
      mechanism between the saccade and reach movements. We observed significant
      correlations between the saccade and reach errors for coordinated movements. In
      contrast, when the eye and arm movements were made to targets in different
      spatial locations, the magnitude of the error and the degree of correlation
      between the saccade and reach direction were determined by the spatial location
      of the eye and the hand targets. Hence, we propose that coordinated movements
      improve reach accuracy without target foveation due to spatial coupling between
      the reach and saccade systems. Spatial coupling could arise from a neural
      mechanism for coordinated visual behavior that involves interacting spatial
      representations.NEW & NOTEWORTHY How visual spatial representations guiding reach
      movements involve coordinated saccadic eye movements is unknown. Temporal
      coupling between the reach and saccade system during coordinated movements
      improves reach performance. However, the role of spatial coupling is unclear.
      Using behavioral psychophysics, we found that spatial coupling increases reach
      accuracy in addition to temporal coupling and visual acuity. These results
      suggest that a spatial mechanism to couple the reach and saccade systems
      increases the accuracy of coordinated movements.

PMID- 28768741
TI  - Theta-frequency selectivity in the somatic spike-triggered average of rat
      hippocampal pyramidal neurons is dependent on HCN channels.
AB  - The ability to distill specific frequencies from complex spatiotemporal patterns
      of afferent inputs is a pivotal functional requirement for neurons residing in
      networks receiving frequency-multiplexed inputs. Although the expression of theta
      frequency subthreshold resonance is established in hippocampal pyramidal neurons,
      it is not known if their spike initiation dynamics manifest spectral selectivity,
      or if their intrinsic properties are tuned to process gamma-frequency inputs.
      Here, we measured the spike-triggered average (STA) of rat hippocampal pyramidal
      neurons through electrophysiological recordings and quantified spectral
      selectivity in their spike initiation dynamics and their coincidence detection
      window (CDW). Our results revealed strong theta-frequency selectivity in the STA,
      which was also endowed with gamma-range CDW, with prominent neuron-to-neuron
      variability that manifested distinct pairwise dissociations and correlations with
      different intrinsic measurements. Furthermore, we demonstrate that the STA and
      its measurements substantially adapted to the state of the neuron defined by its
      membrane potential and to the statistics of its afferent inputs. Finally, we
      tested the effect of pharmacologically blocking the hyperpolarization-activated
      cyclic-nucleotide-gated (HCN) channels on the STA and found that the STA
      characteristic frequency reduced significantly to the delta-frequency band after
      HCN channel blockade. This delta-frequency selectivity in the STA emerged in the
      absence of subthreshold resonance, which was abolished by HCN channel blockade,
      thereby confirming computational predictions on the dissociation between these
      two forms of spectral selectivity. Our results expand the roles of HCN channels
      to theta-frequency selectivity in the spike initiation dynamics, apart from
      underscoring the critical role of interactions among different ion channels in
      regulating neuronal physiology.NEW & NOTEWORTHY We had previously predicted,
      using computational analyses, that the spike-triggered average (STA) of
      hippocampal neurons would exhibit theta-frequency (4-10 Hz) spectral selectivity
      and would manifest coincidence detection capabilities for inputs in the gamma
      frequency band (25-150 Hz). Here, we confirmed these predictions through direct
      electrophysiological recordings of STA from rat CA1 pyramidal neurons and
      demonstrate that blocking HCN channels reduces the frequency of STA spectral
      selectivity to the delta-frequency range (0.5-4 Hz).

PMID- 28768743
TI  - Influence of pain on motor preparation in the human brain.
AB  - The protective function of pain depends on appropriate motor responses to avoid
      injury and promote recovery. The preparation and execution of motor responses is
      thus an essential part of pain. However, it is not yet fully understood how pain
      and motor processes interact in the brain. Here we used electroencephalography to
      investigate the effects of pain on motor preparation in the human brain. Twenty
      healthy human participants performed a motor task in which they performed button
      presses to stop increasingly painful thermal stimuli when they became
      intolerable. In another condition, participants performed button presses without
      concurrent stimulation. The results show that the amplitudes of preparatory event
      related desynchronizations at alpha and beta frequencies did not differ between
      conditions. In contrast, the amplitude of the preparatory readiness potential was
      reduced when a button press was performed to stop a painful stimulus compared
      with a button press without concomitant pain. A control experiment with
      nonpainful thermal stimuli showed a similar reduction of the readiness potential
      when a button press was performed to stop a nonpainful thermal stimulus.
      Together, these findings indicate that painful and nonpainful thermal stimuli can
      similarly influence motor preparation in the human brain. Pain-specific effects
      on motor preparation in the human brain remain to be demonstrated.NEW &
      NOTEWORTHY Pain is inherently linked to motor processes, but the interactions
      between pain and motor processes in the human brain are not yet fully understood.
      Using electroencephalography, we show that pain reduces movement-preparatory
      brain activity. Further results indicate that this effect is not pain specific
      but independent of the modality of stimulation.

PMID- 28768744
TI  - The temporal stability of visuomotor adaptation generalization.
AB  - Movement adaptation in response to systematic motor perturbations exhibits
      distinct spatial and temporal properties. These characteristics are typically
      studied in isolation, leaving the interaction largely unknown. Here we examined
      how the temporal decay of visuomotor adaptation influences the spatial
      generalization of the motor recalibration. First, we quantified the extent to
      which adaptation decayed over time. Subjects reached to a peripheral target, and
      a rotation was applied to the visual feedback of the unseen motion. The retention
      of this adaptation over different delays (0-120 s) 1) decreased by 29.0 +/- 6.8%
      at the longest delay and 2) was represented by a simple exponential, with a time
      constant of 22.5 +/- 5.6 s. On the basis of this relationship we simulated how
      the spatial generalization of adaptation would change with delay. To test this
      directly, we trained additional subjects with the same perturbation and assessed
      transfer to 19 different locations (spaced 15 degrees  apart, symmetric around
      the trained location) and examined three delays (~4, 12, and 25 s). Consistent
      with the simulation, we found that generalization around the trained direction
      (+/-15 degrees ) significantly decreased with delay and distance, while locations
      >60 degrees  displayed near-constant spatiotemporal transfer. Intermediate
      distances (30 degrees  and 45 degrees ) showed a difference in transfer across
      space, but this amount was approximately constant across time. Interestingly, the
      decay at the trained direction was faster than that based purely on time,
      suggesting that the spatial transfer of adaptation is modified by concurrent
      passive (time dependent) and active (movement dependent) processes.NEW &
      NOTEWORTHY Short-term motor adaptation exhibits distinct spatial and temporal
      characteristics. Here we investigated the interaction of these features,
      utilizing a simple motor adaptation paradigm (recalibration of reaching arm
      movements in response to rotated visual feedback). We examined the changes in the
      spatial generalization of motor adaptation for different temporal manipulations
      and report that the spatiotemporal generalization of motor adaptation is
      generally local and is influenced by both passive (time dependent) and active
      (movement dependent) learning processes.

PMID- 28768746
TI  - Oxygen- and capacity-limited thermal tolerance: bridging ecology and physiology.
AB  - Observations of climate impacts on ecosystems highlight the need for an
      understanding of organismal thermal ranges and their implications at the
      ecosystem level. Where changes in aquatic animal populations have been observed,
      the integrative concept of oxygen- and capacity-limited thermal tolerance (OCLTT)
      has successfully characterised the onset of thermal limits to performance and
      field abundance. The OCLTT concept addresses the molecular to whole-animal
      mechanisms that define thermal constraints on the capacity for oxygen supply to
      the organism in relation to oxygen demand. The resulting 'total excess aerobic
      power budget' supports an animal's performance (e.g. comprising motor activity,
      reproduction and growth) within an individual's thermal range. The aerobic power
      budget is often approximated through measurements of aerobic scope for activity
      (i.e. the maximum difference between resting and the highest exercise-induced
      rate of oxygen consumption), whereas most animals in the field rely on lower
      (i.e. routine) modes of activity. At thermal limits, OCLTT also integrates
      protective mechanisms that extend time-limited tolerance to temperature extremes 
      mechanisms such as chaperones, anaerobic metabolism and antioxidative defence.
      Here, we briefly summarise the OCLTT concept and update it by addressing the role
      of routine metabolism. We highlight potential pitfalls in applying the concept
      and discuss the variables measured that led to the development of OCLTT. We
      propose that OCLTT explains why thermal vulnerability is highest at the whole
      animal level and lowest at the molecular level. We also discuss how OCLTT
      captures the thermal constraints on the evolution of aquatic animal life and
      supports an understanding of the benefits of transitioning from water to land.

PMID- 28768747
TI  - How innate is locomotion in precocial animals? A study on the early development
      of spatio-temporal gait variables and gait symmetry in piglets.
AB  - Locomotion is one of the most important ecological functions in animals.
      Precocial animals, such as pigs, are capable of independent locomotion shortly
      after birth. This raises the question whether coordinated movement patterns and
      the underlying muscular control in these animals is fully innate or whether there
      still exists a rapid maturation. We addressed this question by studying gait
      development in neonatal pigs through the analysis of spatio-temporal gait
      characteristics during locomotion at self-selected speed. To this end, we made
      video recordings of piglets walking along a corridor at several time points (from
      0 h to 96 h). After digitization of the footfalls, we analysed self-selected
      speed and spatio-temporal characteristics (e.g. stride and step lengths, stride
      frequency and duty factor) to study dynamic similarity, intralimb coordination
      and interlimb coordination. To assess the variability of the gait pattern, left
      right asymmetry was studied. To distinguish neuromotor maturation from effects
      caused by growth, both absolute and normalized data (according to the dynamic
      similarity concept) were included in the analysis. All normalized spatio-temporal
      variables reached stable values within 4 h of birth, with most of them showing
      little change after the age of 2 h. Most asymmetry indices showed stable values,
      hovering around 10%, within 8 h of birth. These results indicate that coordinated
      movement patterns are not entirely innate, but that a rapid neuromotor
      maturation, potentially also the result of the rearrangement or recombination of
      existing motor modules, takes place in these precocial animals.

PMID- 28768745
TI  - Altered modulation of sensorimotor rhythms with chronic paralysis.
AB  - After paralysis, the disconnection between the cortex and its peripheral targets
      leads to neuroplasticity throughout the nervous system. However, it is unclear
      how chronic paralysis specifically impacts cortical oscillations associated with
      attempted movement of impaired limbs. We hypothesized that MU- (8-13 Hz) and beta
      (15-30 Hz) event-related desynchronization (ERD) would be less modulated for
      individuals with hand paralysis due to cervical spinal cord injury (SCI). To test
      this, we compared the modulation of ERD from magnetoencephalography (MEG) during
      attempted and imagined grasping performed by participants with cervical SCI (n =
      12) and able-bodied controls (n = 13). Seven participants with tetraplegia were
      able to generate some electromyography (EMG) activity during attempted grasping,
      whereas the other five were not. The peak and area of ERD were significantly
      decreased for individuals without volitional muscle activity when they attempted
      to grasp compared with able-bodied subjects and participants with SCI,with some
      residual EMG activity. However, no significant differences were found between
      subject groups during mentally simulated tasks (i.e., motor imagery) where no
      muscle activity or somatosensory consequences were expected. These findings
      suggest that individuals who are unable to produce muscle activity are capable of
      generating ERD when attempting to move, but the characteristics of this ERD are
      altered. However, for people who maintain volitional muscle activity after SCI,
      there are no significant differences in ERD characteristics compared with able
      bodied controls. These results provide evidence that ERD is dependent on the
      level of intact muscle activity after SCI.NEW & NOTEWORTHY Source space MEG was
      used to investigate sensorimotor cortical oscillations in individuals with SCI.
      This study provides evidence that individuals with cervical SCI exhibit decreased
      ERD when they attempt to grasp if they are incapable of generating muscle
      activity. However, there were no significant differences in ERD between paralyzed
      and able-bodied participants during motor imagery. These results have important
      implications for the design and evaluation of new therapies, such as motor
      imagery and neurofeedback interventions.

PMID- 28768748
TI  - Upper lethal temperatures in three cold-tolerant insects are higher in winter
      than in summer.
AB  - Upper lethal temperatures (ULTs) of cold-adapted insect species in winter have
      not been previously examined. We anticipated that as the lower lethal
      temperatures (LLTs) decreased (by 20-30 degrees C) with the onset of winter, the
      ULTs would also decrease accordingly. Consequently, given the recent increases in
      winter freeze-thaw cycles and warmer winters due to climate change, it became of
      interest to determine whether ambient temperatures during thaws were approaching
      ULTs during the cold seasons. However, beetle Dendroides canadensis (Coleoptera:
      Pyrochroidae) larvae had higher 24 and 48 h ULT50 (the temperature at which 50%
      mortality occurred) in winter than in summer. The 24 and 48 h ULT50 for D.
      canadensis in winter were 40.9 and 38.7 degrees C, respectively. For D.
      canadensis in summer, the 24 and 48 h ULT50 were 36.7 and 36.4 degrees C. During
      the transition periods of spring and autumn, the 24 h ULT50 was 37.3 and 38.5
      degrees C, respectively. While D. canadensis in winter had a 24 h LT50 range
      between LLT and ULT of 64 degrees C, the summer range was only 41 degrees C.
      Additionally, larvae of the beetle Cucujus clavipes clavipes (Coleoptera:
      Cucujidae) and the cranefly Tipula trivittata (Diptera: Tipulidae) also had
      higher ULTs in winter than in summer. This unexpected phenomenon of increased
      temperature survivorship at both lower and higher temperatures in the winter
      compared with that in the summer has not been previously documented. With the
      decreased high temperature tolerance as the season progresses from winter to
      summer, it was observed that environmental temperatures are closest to upper
      lethal temperatures in spring.

PMID- 28768749
TI  - Orientation of native versus translocated juvenile lesser spotted eagles (Clanga
      pomarina) on the first autumn migration.
AB  - The ontogeny of migration routines used by wild birds remains unresolved. Here we
      investigated the migratory orientation of juvenile lesser spotted eagles (LSE;
      Clanga pomarina) based on translocation and satellite tracking. Between 2004 and
      2016, 85 second-hatched juveniles (Abels) were reared in captivity for release
      into the declining German population, including 50 birds that were translocated
      940 km from Latvia. In 2009, we tracked 12 translocated juveniles, as well as
      eight native juveniles and nine native adults, to determine how inexperienced
      birds come to use strategic migration routes. Native juveniles departed around
      the same time as the adults and six of eight used the eastern flyway around the
      Mediterranean, which was used by all adults. In contrast, translocated juveniles
      departed on average 6 days before native LSEs, and five travelled southward and
      died in the central Mediterranean region. Consequently, fewer translocated
      juveniles (4/12) than native juveniles (7/8) reached Africa. We conclude that
      juvenile LSEs have a much better chance of learning the strategic southeastern
      flyway if they leave at an appropriate time to connect with experienced elders
      upon departure. It is not clear why translocated juveniles departed so early.
      Regardless, by the end of the year, most juveniles had perished, whether they
      were translocated (10/12) or not (6/8). The small number of surviving
      translocated juveniles thus still represents a significant increase in the annual
      productivity of the German LSE population in 2009.

PMID- 28768750
TI  - Echo-acoustic scanning with noseleaf and ears in phyllostomid bats.
AB  - The mammalian visual system is highly directional and mammals typically employ
      rapid eye movements to scan their environment. Both sound emission and hearing in
      echolocating bats are directional but not much is known about how bats use ear
      movements and possibly movements of the sound-emitting structures to scan space.
      Here, we investigated in a tightly controlled behavioural experiment how
      Phyllostomusdiscolor bats employ their echolocation system while being moved
      through differently structured environments: we monitored and reconstructed both
      a close-up of the facial structures in 3D, including the motile noseleaf and
      outer ears, and the sonar-beam of the bat while it was moved along reflectors.
      Despite the simple linear movement of the bats in the setup, the bats pointed
      their beam quite variably in azimuth with a standard deviation of about +/-20
      deg. This variation arises from yaw-type head rotations. Video analyses show that
      the bat's noseleaf twitches with every echolocation call. Second, we show that
      the bat's ears are raised to a rather stereotypical head-centred position with
      every echolocation call. Surprisingly, P. discolor can adjust the timing and the
      magnitude of these ear movements to the distance of the reflectors with
      millisecond precision. Our findings reveal echolocation-specific specialisations
      as well as general principles of scanning and stabilisation of a directional
      remote sense. The call-correlated movements of the facial structures may lead to
      a higher directionality of the echolocation system and may enable the bats to
      adjust their echo-acoustic gaze to dynamic environments.

PMID- 28768751
TI  - Loss of Y Chromosome in Blood Is Associated With Major Cardiovascular Events
      During Follow-Up in Men After Carotid Endarterectomy.
AB  - BACKGROUND: Recent studies found an immune regulatory role for Y chromosome and a
      relationship between loss of Y chromosome (LOY) in blood cells and a higher risk
      of cancer and mortality. Given involvement of immune cells in atherosclerosis, we
      hypothesized that LOY is associated with the severity of atherosclerotic plaque
      characteristics and outcome in men undergoing carotid endarterectomy. METHODS AND
      RESULTS: LOY was quantified in blood and plaque from raw intensity genotyping
      data in men within the Athero-Express biobank study. Plaques were dissected, and
      the culprit lesions used for histology and the measurement of inflammatory
      proteins. We tested LOY for association with (inflammatory) atherosclerotic
      plaque phenotypes and cytokines and assessed the association of LOY with
      secondary events during 3-year follow-up. Of 366 patients with carotid
      endarterectomy, 61 exhibited some degree of LOY in blood. LOY was also present in
      atherosclerotic plaque lesions (n=8/242, 3%). LOY in blood was negatively
      associated with age (beta=-0.03/10 y; r2=0.07; P=1.6*10-7) but not with
      cardiovascular disease severity at baseline. LOY in blood was associated with a
      larger atheroma size (odds ratio, 2.15; 95% confidence interval, 1.06-4.76;
      P=0.04); however, this association was not significant after correction for
      multiple testing. LOY was independently associated with secondary major
      cardiovascular events (hazard ratio=2.28; 95% confidence interval, 1.11-4.67;
      P=0.02) in blood when corrected for confounders. CONCLUSIONS: In this hypothesis
      generating study, LOY in blood is independently associated with secondary major
      cardiovascular events in a severely atherosclerotic population. Our data could
      indicate that LOY affects secondary outcome via other mechanisms than
      inflammation in the atherosclerotic plaque.

PMID- 28768752
TI  - Cardiovascular Disease and Long Noncoding RNAs: Tools for Unraveling the Mystery
      Lnc-ing RNA and Phenotype.

PMID- 28768754
TI  - Previously Unreported in Women Galactosidase Alpha Pro409Ser Variant Is
      Associated With Fabry Disease.

PMID- 28768755
TI  - Loss of Chromosome Y in Leukocytes and Major Cardiovascular Events.

PMID- 28768753
TI  - PCSK9 Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of
      Coronary Heart Disease and Stroke: Data From 9 Studies of Blacks and Whites.
AB  - BACKGROUND: PCSK9 loss-of-function (LOF) variants allow for the examination of
      the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on
      cardiovascular events. We examined the association of PCSK9 LOF variants with LDL
      C and incident coronary heart disease and stroke through a meta-analysis of data
      from 8 observational cohorts and 1 randomized trial of statin therapy. METHODS
      AND RESULTS: These 9 studies together included 17 459 blacks with 403 (2.3%)
      having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having
      at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9
      LOF variants and incident coronary heart disease (851 events in blacks and 2662
      events in whites) and stroke (523 events in blacks and 1660 events in whites)
      were calculated using pooled Mantel-Haenszel estimates with continuity correction
      factors. Pooling results across studies using fixed-effects inverse-variance
      weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence
      interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower
      LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for
      coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI,
      0.63-1.06) in whites. PCSK9 LOF variants were not associated with incident stroke
      (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80
      1.41 in whites). CONCLUSIONS: PCSK9 LOF variants were associated with lower LDL-C
      and coronary heart disease incidence. PCSK9 LOF variants were not associated with
      stroke risk.

PMID- 28768757
TI  - Optimized Screening of Coronary Artery Disease With Invasive Coronary Angiography
      and Ad Hoc Percutaneous Coronary Intervention During Transcatheter Aortic Valve
      Replacement.
AB  - BACKGROUND: We sought to describe an optimized approach to coronary artery
      disease (CAD) screening and management in patients undergoing transcatheter
      aortic valve replacement (TAVR). METHODS AND RESULTS: When invasive coronary
      angiography showed CAD, the treatment strategy and completeness of
      revascularization was determined based on coronary anatomy. TAVR was performed in
      the same setting if percutaneous coronary intervention (PCI) was uncomplicated;
      otherwise TAVR was postponed. A total of 604 patients undergoing CAD screening at
      the time of TAVR procedure were prospectively included in this study. Severe CAD
      was found in 136 patients (22.5%). Among patients with severe CAD, 53 patients
      (8.8%) underwent uncomplicated PCI. After PCI, TAVR was postponed in 2 patients
      (0.3%). In 83 patients (13.8%), coronary angiography showed severe CAD that was
      left untreated. After TAVR, all-cause and cardiovascular 30-day mortality rates
      were 2.4% and 1.4%, respectively. Disabling stroke, myocardial infarction, and
      life-threatening bleeding occurred in 0.5%, 0.8%, and 4.0% of patients,
      respectively. Acute kidney injury II or III rate was 3.3%. At 2 years, all-cause
      mortality rate was 14.1%. Disabling stroke and myocardial infarction occurred in
      2.5% and 1.8% of patients, respectively. Patients undergoing TAVR and PCI in the
      same session had similar rate of the composite of death, disabling stroke, and
      myocardial infarction when compared with patients without CAD, and patients with
      severe CAD left untreated (TAVR+PCI: 10.4%; severe CAD left untreated: 15.4%; no
      CAD: 14.8%; P=0.765). CONCLUSIONS: In patients undergoing TAVR, screening of CAD
      with invasive coronary angiography and ad hoc PCI during TAVR is feasible and was
      not associated with increased periprocedural risks. PCI followed by TAVR in the
      same session had similar outcomes than TAVR in which PCI was not performed.

PMID- 28768756
TI  - Impact of Timing on the Functional Recovery Achieved With Platelet
      Supplementation After Treatment With Ticagrelor.
AB  - BACKGROUND: American College of Cardiology/American Heart Association guidelines
      advise waiting 5 to 7 days before operating on P2Y12 inhibitor-treated acute
      coronary syndrome patients, to allow dissipation of its antiplatelet effects.
      Platelet transfusion is often used to restore hemostasis during operations, but
      its effectiveness and optimal timing are unclear. We investigated the degree of
      functional gains obtained from platelet supplementation after loading and
      maintenance of dual antiplatelet therapy with ticagrelor and the influence of
      timing on this strategy. METHODS AND RESULTS: After baseline platelet testing
      (Multiplate Analyzer and VerifyNow), cardiovascular disease patients (n=20;
      56.9+/-7.9 years; 65% men; 75% diabetic) received dual antiplatelet therapy as a
      single loading dose (ticagrelor 180 mg plus aspirin 325 mg) and as
      daily/maintenance treatment for 5 to 7 days (maintenance therapy: ticagrelor 90
      mg BID plus aspirin 81 mg QD). At 4, 6, 24, and 48 hours from (last) dosing,
      patients' blood samples were supplemented with concentrated platelets from
      healthy donors in vitro, raising platelet counts by 0% (unsupplemented control),
      25%, 50%, and 75%, and the function retested. Reactivity in supplemented samples
      was compared with respective 0% sample and with the pretreatment baseline.
      Results under loading dose and maintenance therapy regimens were nearly
      identical. Platelet reactivity was higher (P<0.05) in nearly all supplemented
      samples versus respective controls. Aggregations with supplementation were 59% to
      79% of baseline at 24 hours and equal to baseline at 48 hours. CONCLUSIONS:
      Platelet reactivity of ticagrelor-treated patients can be restored using
      concentrated platelets after a loading dose/maintenance therapy in a time
      dependent manner under in vitro testing. Although statistically significant
      improvements are evident 6 hours after (last) dosing, >=24 hours maybe needed for
      clinically meaningful restoration in platelet function. CLINICAL TRIAL
      REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02201394.

PMID- 28768758
TI  - Low Endothelial Shear Stress Predicts Evolution to High-Risk Coronary Plaque
      Phenotype in the Future: A Serial Optical Coherence Tomography and Computational
      Fluid Dynamics Study.
AB  - BACKGROUND: Low endothelial shear stress (ESS) is associated with plaque
      progression and vulnerability. To date, changes in plaque phenotype over time in
      relation to ESS have not been studied in humans. The aim of this study was to
      investigate whether local ESS can predict subsequent changes to plaque phenotype
      using optical coherence tomography. METHODS AND RESULTS: A total of 25 coronary
      arteries from 20 patients who underwent baseline and 6-month follow-up optical
      coherence tomography were included. Arteries were divided into serial 3-mm
      segments, and plaque characteristics were evaluated in each segment. A total of
      145 segments were divided into low-ESS group (ESS <1 Pa) and higher-ESS group
      (ESS >=1 Pa) based on baseline computational flow dynamics analyses. At baseline,
      low-ESS segments had significantly thinner fibrous cap thickness compared with
      higher-ESS segments (128.2+/-12.3 versus 165.0+/-12.0 MUm; P=0.03), although
      lipid arc was similar. At follow-up, fibrous cap thickness remained thin in low
      ESS segments, whereas it significantly increased in higher-ESS segments (165.0+/
      12.0 to 182.2+/-14.1 MUm; P=0.04). Lipid arc widened only in plaques with low ESS
      (126.4+/-15.2 degrees  to 141.1+/-14.0 degrees ; P=0.01). After adjustment,
      baseline ESS was associated with fibrous cap thickness (beta, 9.089; 95%
      confidence interval, 2.539-15.640; P=0.007) and lipid arc (beta, -4.381; 95%
      confidence interval, -6.946 to -1.815; P=0.001) at follow-up. CONCLUSIONS: Low
      ESS is significantly associated with baseline high-risk plaque phenotype and
      progression to higher-risk phenotype at 6 months. CLINICAL TRIAL REGISTRATION:
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.

PMID- 28768759
TI  - Letter by Kounis et al Regarding Article, "Long-Term Efficacy and Safety of
      Everolimus-Eluting Bioresorbable Vascular Scaffolds Versus Everolimus-Eluting
      Metallic Stents: A Meta-Analysis of Randomized Trials".

PMID- 28768760
TI  - Platelet Transfusion for Ticagrelor Reversal.

PMID- 28768761
TI  - Combining Transcatheter Aortic Valve Replacement and Coronary
      Angiography/Percutaneous Coronary Intervention Procedures: Ready for Prime Time?

PMID- 28768762
TI  - Response by Mahmoud et al to Letter Regarding Article, "Long-Term Efficacy and
      Safety of Everolimus-Eluting Bioresorbable Vascular Scaffolds Versus Everolimus
      Eluting Metallic Stents: A Meta-Analysis of Randomized Trials".

PMID- 28768763
TI  - A solute-binding protein in the closed conformation induces ATP hydrolysis in a
      bacterial ATP-binding cassette transporter involved in the import of alginate.
AB  - The Gram-negative bacterium Sphingomonas sp. A1 incorporates alginate into cells
      via the cell-surface pit without prior depolymerization by extracellular enzymes.
      Alginate import across cytoplasmic membranes thereby depends on the ATP-binding
      cassette transporter AlgM1M2SS (a heterotetramer of AlgM1, AlgM2, and AlgS),
      which cooperates with the periplasmic solute-binding protein AlgQ1 or AlgQ2;
      however, several details of AlgM1M2SS-mediated alginate import are not well
      understood. Herein, we analyzed ATPase and transport activities of AlgM1M2SS
      after reconstitution into liposomes with AlgQ2 and alginate oligosaccharide
      substrates having different polymerization degrees (PDs). Longer alginate
      oligosaccharides (PD >= 5) stimulated the ATPase activity of AlgM1M2SS but were
      inert as substrates of AlgM1M2SS-mediated transport, indicating that AlgM1M2SS
      mediated ATP hydrolysis can be stimulated independently of substrate transport.
      Using X-ray crystallography in the presence of AlgQ2 and long alginate
      oligosaccharides (PD 6-8) and with the humid air and glue-coating method, we
      determined the crystal structure of AlgM1M2SS in complex with oligosaccharide
      bound AlgQ2 at 3.6 A resolution. The structure of the ATP-binding cassette
      transporter in complex with non-transport ligand-bound periplasmic solute-binding
      protein revealed that AlgM1M2SS and AlgQ2 adopt inward-facing and closed
      conformations, respectively. These in vitro assays and structural analyses
      indicated that interactions between AlgM1M2SS in the inward-facing conformation
      and periplasmic ligand-bound AlgQ2 in the closed conformation induce ATP
      hydrolysis by the ATP-binding protein AlgS. We conclude that substrate-bound
      AlgQ2 in the closed conformation initially interacts with AlgM1M2SS, the
      AlgM1M2SS-AlgQ2 complex then forms, and this formation is followed by ATP
      hydrolysis.

PMID- 28768764
TI  - Src homology 2 domain-containing phosphotyrosine phosphatase 2 (Shp2) controls
      surface GluA1 protein in synaptic homeostasis.
AB  - Src Homology 2 domain-containing phosphotyrosine phosphatase 2 (Shp2) functions
      in synaptic plasticity, learning, and memory. However, the precise mechanisms by
      which this multifunctional protein contributes to synaptic function remains
      largely unknown. Homeostatic plasticity may be viewed as a process of
      bidirectional synaptic scaling, up or down. Through this process, neuronal
      circuitry stability is maintained so that changes in synaptic strength may be
      preserved under changing conditions. A better understanding of these processes is
      needed. In this regard, we report that phosphorylation of Shp2 at tyrosine 542
      and its translocation to the postsynaptic compartment are integral processes in
      synaptic scaling. Furthermore, we show, using both pharmacological and genetic
      approaches, that Shp2 phosphatase activity is critical to the regulation of
      Ser(P)845 GluA1 and surface expression of this AMPA receptor subunit during
      synaptic scaling. Thus, Shp2 may contribute meaningfully to synaptic homeostasis.

PMID- 28768765
TI  - Crystal structures of TdsC, a dibenzothiophene monooxygenase from the thermophile
      Paenibacillus sp. A11-2, reveal potential for expanding its substrate
      selectivity.
AB  - Sulfur compounds in fossil fuels are a major source of environmental pollution,
      and microbial desulfurization has emerged as a promising technology for removing
      sulfur under mild conditions. The enzyme TdsC from the thermophile Paenibacillus
      sp. A11-2 is a two-component flavin-dependent monooxygenase that catalyzes the
      oxygenation of dibenzothiophene (DBT) to its sulfoxide (DBTO) and sulfone (DBTO2)
      during microbial desulfurization. The crystal structures of the apo and flavin
      mononucleotide (FMN)-bound forms of DszC, an ortholog of TdsC, were previously
      determined, although the structure of the ternary substrate-FMN-enzyme complex
      remains unknown. Herein, we report the crystal structures of the DBT-FMN-TdsC and
      DBTO-FMN-TdsC complexes. These ternary structures revealed many hydrophobic and
      hydrogen-bonding interactions with the substrate, and the position of the
      substrate could reasonably explain the two-step oxygenation of DBT by TdsC. We
      also determined the crystal structure of the indole-bound enzyme because TdsC,
      but not DszC, can also oxidize indole, and we observed that indole binding did
      not induce global conformational changes in TdsC with or without bound FMN. We
      also found that the two loop regions close to the FMN-binding site are disordered
      in apo-TdsC and become structured upon FMN binding. Alanine substitutions of Tyr
      93 and His-388, which are located close to the substrate and FMN bound to TdsC,
      significantly decreased benzothiophene oxygenation activity, suggesting their
      involvement in supplying protons to the active site. Interestingly, these
      substitutions increased DBT oxygenation activity by TdsC, indicating that
      expanding the substrate-binding site can increase the oxygenation activity of
      TdsC on larger sulfur-containing substrates, a property that should prove useful
      for future microbial desulfurization applications.

PMID- 28768766
TI  - A synergistic role of IRP1 and FBXL5 proteins in coordinating iron metabolism
      during cell proliferation.
AB  - Iron-regulatory protein 1 (IRP1) belongs to a family of RNA-binding proteins that
      modulate metazoan iron metabolism. Multiple mechanisms are employed to control
      the action of IRP1 in dictating changes in the uptake and metabolic fate of iron.
      Inactivation of IRP1 RNA binding by iron primarily involves insertion of a [4Fe
      4S] cluster by the cytosolic iron-sulfur cluster assembly (CIA) system,
      converting it into cytosolic aconitase (c-acon), but can also involve iron
      mediated degradation of IRP1 by the E3 ligase FBXL5 that also targets IRP2. How
      CIA and FBXL5 collaborate to maintain cellular iron homeostasis through IRP1 and
      other pathways is poorly understood. Because impaired Fe-S cluster biogenesis
      associates with human disease, we determined the importance of FBXL5 for
      regulating IRP1 when CIA is impaired. Suppression of FBXL5 expression coupled
      with induction of an IRP1 mutant (IRP13C>3S) that cannot insert the Fe-S cluster,
      or along with knockdown of the CIA factors NUBP2 or FAM96A, reduced cell
      viability. Iron supplementation reversed this growth defect and was associated
      with FBXL5-dependent polyubiquitination of IRP1. Phosphorylation of IRP1 at Ser
      138 increased when CIA was inhibited and was required for iron rescue. Impaired
      CIA activity, as noted by reduced c-acon activity, was associated with enhanced
      FBXL5 expression and a concomitant reduction in IRP1 and IRP2 protein level and
      RNA-binding activity. Conversely, expression of either IRP induced FBXL5 protein
      level, demonstrating a negative feedback loop limiting excessive accumulation of
      iron-response element RNA-binding activity, whose disruption reduces cell growth.
      We conclude that a regulatory circuit involving FBXL5 and CIA acts through both
      IRPs to control iron metabolism and promote optimal cell growth.

PMID- 28768767
TI  - Iron is a substrate of the Plasmodium falciparum chloroquine resistance
      transporter PfCRT in Xenopus oocytes.
AB  - The chloroquine resistance transporter of the human malaria parasite Plasmodium
      falciparum, PfCRT, is an important determinant of resistance to several quinoline
      and quinoline-like antimalarial drugs. PfCRT also plays an essential role in the
      physiology of the parasite during development inside erythrocytes. However, the
      function of this transporter besides its role in drug resistance is still
      unclear. Using electrophysiological and flux experiments conducted on PfCRT
      expressing Xenopus laevis oocytes, we show here that both wild-type PfCRT and a
      PfCRT variant associated with chloroquine resistance transport both ferrous and
      ferric iron, albeit with different kinetics. In particular, we found that the
      ability to transport ferrous iron is reduced by the specific polymorphisms
      acquired by the PfCRT variant as a result of chloroquine selection. We further
      show that iron and chloroquine transport via PfCRT is electrogenic. If these
      findings in the Xenopus model extend to P. falciparum in vivo, our data suggest
      that PfCRT might play a role in iron homeostasis, which is essential for the
      parasite's development in erythrocytes.

PMID- 28768768
TI  - Regulation of the epithelial Na+ channel by paraoxonase-2.
AB  - Paraoxonase-2 (PON-2) is a membrane-bound lactonase with unique anti-oxidative
      and anti-atherosclerotic properties. PON-2 shares key structural elements with
      MEC-6, an endoplasmic reticulum-resident molecular chaperone in Caenorhabditis
      elegans MEC-6 modulates the expression of a mechanotransductive ion channel
      comprising MEC-4 and MEC-10 in touch-receptor neurons. Because pon-2 mRNA resides
      in multiple rat nephron segments, including the aldosterone-sensitive distal
      nephron where the epithelial Na+ channel (ENaC) is expressed, we hypothesized
      that PON-2 would similarly regulate ENaC expression. We observed PON-2 expression
      in aquaporin 2-positive principal cells of the distal nephron of adult human
      kidney. PON-2 also co-immunoprecipitated with ENaC when co-expressed in HEK293
      cells. When PON-2 was co-expressed with ENaC in Xenopus oocytes, ENaC activity
      was reduced, reflecting a reduction in ENaC surface expression. MEC-6 also
      reduced ENaC activity when co-expressed in Xenopus oocytes. The PON-2 inhibitory
      effect was ENaC-specific, as PON-2 had no effect on functional expression of the
      renal outer medullary potassium channel. PON-2 did not alter the response of ENaC
      to extracellular Na+, mechanical shear stress, or alpha-chymotrypsin-mediated
      proteolysis, suggesting that PON-2 did not alter the regulation of ENaC by these
      factors. Together, our data suggest that PON-2 regulates ENaC activity by
      modulating its intracellular trafficking and surface expression.

PMID- 28768769
TI  - Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is necessary
      for prostate cancer metastasis via epithelial-mesenchymal transition.
AB  - Prostate cancer is a highly penetrant disease among men in industrialized
      societies, but the factors regulating the transition from indolent to aggressive
      and metastatic cancer remain poorly understood. We found that men with prostate
      cancers expressing high levels of the G protein-coupled receptor LGR4 had a
      significantly shorter recurrence-free survival compared with patients with
      cancers having low LGR4 expression. LGR4 expression was elevated in human
      prostate cancer cell lines with metastatic potential. We therefore generated a
      novel transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model to
      investigate the role of Lgr4 in prostate cancer development and metastasis in
      vivo TRAMP Lgr4-/- mice exhibited an initial delay in prostate intraepithelial
      neoplasia formation, but the frequency of tumor formation was equivalent between
      TRAMP and TRAMP Lgr4-/- mice by 12 weeks. The loss of Lgr4 significantly improved
      TRAMP mouse survival and dramatically reduced the occurrence of lung metastases.
      LGR4 knockdown impaired the migration, invasion, and colony formation of DU145
      cells and reversed epithelial-mesenchymal transition (EMT), as demonstrated by up
      regulation of E-cadherin and decreased expression of the EMT transcription
      factors ZEB, Twist, and Snail. Overexpression of LGR4 in LNCaP cells had the
      opposite effects. Orthotopic injection of DU145 cells stably expressing shRNA
      targeting LGR4 resulted in decreased xenograft tumor size, reduced tumor EMT
      marker expression, and impaired metastasis, in accord with our findings in TRAMP
      Lgr4-/- mice. In conclusion, we propose that Lgr4 is a key protein necessary for
      prostate cancer EMT and metastasis.

PMID- 28768770
TI  - NMDA receptors mediate leptin signaling and regulate potassium channel
      trafficking in pancreatic beta-cells.
AB  - NMDA receptors (NMDARs) are Ca2+-permeant, ligand-gated ion channels activated by
      the excitatory neurotransmitter glutamate and have well-characterized roles in
      the nervous system. The expression and function of NMDARs in pancreatic beta
      cells, by contrast, are poorly understood. Here, we report a novel function of
      NMDARs in beta-cells. Using a combination of biochemistry, electrophysiology, and
      imaging techniques, we now show that NMDARs have a key role in mediating the
      effect of leptin to modulate beta-cell electrical activity by promoting AMP
      activated protein kinase (AMPK)-dependent trafficking of KATP and Kv2.1 channels
      to the plasma membrane. Blocking NMDAR activity inhibited the ability of leptin
      to activate AMPK, induce KATP and Kv2.1 channel trafficking, and promote membrane
      hyperpolarization. Conversely, activation of NMDARs mimicked the effect of
      leptin, causing Ca2+ influx, AMPK activation, and increased trafficking of KATP
      and Kv2.1 channels to the plasma membrane, and triggered membrane
      hyperpolarization. Moreover, leptin potentiated NMDAR currents and triggered
      NMDAR-dependent Ca2+ influx. Importantly, NMDAR-mediated signaling was observed
      in rat insulinoma 832/13 cells and in human beta-cells, indicating that this
      pathway is conserved across species. The ability of NMDARs to regulate potassium
      channel surface expression and thus, beta-cell excitability provides mechanistic
      insight into the recently reported insulinotropic effects of NMDAR antagonists
      and therefore highlights the therapeutic potential of these drugs in managing
      type 2 diabetes.

PMID- 28768771
TI  - Activation of mas-related G-protein-coupled receptors by the house dust mite
      cysteine protease Der p1 provides a new mechanism linking allergy and
      inflammation.
AB  - Cysteine and serine proteases function via protease-activated and mas-related G
      protein-coupled receptors (Mrgprs) to contribute to allergy and inflammation. Der
      p1 is a cysteine protease and major allergen from the house dust mite and is
      associated with allergic rhinitis and allergic asthma. Der p1 activates protease
      activated receptor 2 and induces the release of the pro-inflammatory cytokine IL
      6 from cells. However, the possibility that Der p1 acts on Mrgprs has not been
      considered. We report here that ratiometric calcium imaging reveals that Der p1
      activates the human receptor MRGPRX1 and the mouse homolog MrgprC11, implicated
      previously in itch. Der p1 cleavage of N-terminal receptor peptides followed by
      site-directed mutagenesis of the cleavage sites links receptor activation to
      specific amino acid residues. Der p1 also induced the release of IL-6 from
      heterologous cells expressing MRGPRX1. In summary, activation of Mrgprs by the
      allergen Der p1 may contribute to inflammation.

PMID- 28768773
TI  - Ceramics in total hip arthroplasty: a bearing solution?

PMID- 28768774
TI  - The use of highly crosslinked polyethylene in total knee arthroplasty.
AB  - Advances in polyethylene (PE) in total hip arthroplasty have led to interest and
      increased use of highly crosslinked PE (HXLPE) in total knee arthroplasty (TKA).
      Biomechanical data suggest improved wear characteristics for HXLPE inserts over
      conventional PE in TKA. Short-term results from registry data and few clinical
      trials are promising. Our aim is to present a review of the history of HXLPEs,
      the use of HXLPE inserts in TKA, concerns regarding potential mechanical
      complications, and a thorough review of the available biomechanical and clinical
      data. Cite this article: Bone Joint J 2017;99-B:996-1002.

PMID- 28768775
TI  - The surgical treatment of non-specific low back pain.
AB  - The National Institute for Health and Care Excellence has issued guidelines that
      state fusion for non-specific low back pain should only be performed as part of a
      randomised controlled trial, and that lumbar disc replacement should not be
      performed. Thus, spinal fusion and disc replacement will no longer be routine
      forms of treatment for patients with low back pain. This annotation considers the
      evidence upon which these guidelines are based. Cite this article: Bone Joint J
      2017;99-B:1003-1005.

PMID- 28768772
TI  - A computational combinatorial approach identifies a protein inhibitor of
      superoxide dismutase 1 misfolding, aggregation, and cytotoxicity.
AB  - Molecular agents that specifically bind and neutralize misfolded and toxic
      superoxide dismutase 1 (SOD1) mutant proteins may find application in attenuating
      the disease progression of familial amyotrophic lateral sclerosis. However, high
      structural similarities between the wild-type and mutant SOD1 proteins limit the
      utility of this approach. Here we addressed this challenge by converting a
      promiscuous natural human IgG-binding domain, the hyperthermophilic variant of
      protein G (HTB1), into a highly specific aggregation inhibitor (designated HTB1M)
      of two familial amyotrophic lateral sclerosis-linked SOD1 mutants, SOD1G93A and
      SOD1G85R We utilized a computational algorithm for mapping protein surfaces
      predisposed to HTB1 intermolecular interactions to construct a focused HTB1
      library, complemented with an experimental platform based on yeast surface
      display for affinity and specificity screening. HTB1M displayed high binding
      specificity toward SOD1 mutants, inhibited their amyloid aggregation in vitro,
      prevented the accumulation of misfolded proteins in living cells, and reduced the
      cytotoxicity of SOD1G93A expressed in motor neuron-like cells. Competition assays
      and molecular docking simulations suggested that HTB1M binds to SOD1 via both its
      alpha-helical and beta-sheet domains at the native dimer interface that becomes
      exposed upon mutated SOD1 misfolding and monomerization. Our results demonstrate
      the utility of computational mapping of the protein-protein interaction potential
      for designing focused protein libraries to be used in directed evolution. They
      also provide new insight into the mechanism of conversion of broad-spectrum
      immunoglobulin-binding proteins, such as HTB1, into target-specific proteins,
      thereby paving the way for the development of new selective drugs targeting the
      amyloidogenic proteins implicated in a variety of human diseases.

PMID- 28768776
TI  - The validity and reproducibility of cross table radiographs compared with CT
      scans for the measurement of anteversion of the acetabular component after total
      hip arthroplasty.
AB  - AIMS: The aim of this study was to assess the reproducibility and validity of
      cross table radiographs for measuring the anteversion of the acetabular component
      after total hip arthroplasty (THA) and to compare it with measurements using CT
      scans. PATIENTS AND METHODS: A total of 29 patients who underwent THA between
      June 2010 and January 2016 were included. There were 17 men and 12 women. Their
      mean age was 43 years (26 to 65). Seven patients underwent a bilateral procedure.
      Thus, 36 THAs were included in the study. Lateral radiographs and CT scans were
      obtained post-operatively and radiographs repeated three weeks later. The
      anteversion of the acetabular component was measured using the method described
      by Woo and Morrey and the ischiolateral method described by Pulos et al and these
      were compared with the results obtained from CT scans. RESULTS: The mean
      anteversion was 18.35 degrees  (3 degrees  to 38 degrees ) using Woo and Morrey's
      method, 51.45 degrees  (30 degrees  to 85 degrees ) using the ischiolateral
      method and 21.22 degrees  (2 degrees  to 48 degrees ) using CT scans. The Pearson
      correlation coefficient was 0.754 for Woo and Morrey's method and 0.925 for the
      ischiolateral method. There was a linear correlation between the measurements
      using the ischiolateral method and those using CT scans. We derived a simple
      linear equation between the value of the CT scan and that of ischiolateral method
      to deduce the CT scan value from that of ischiolateral method and vice versa.
      CONCLUSION: The anteversion of the acetabular component measured using both plain
      radiographic methods was consistently valid with good interobserver
      reproducibility, but the ischiolateral method which is independent of pelvic tilt
      was more accurate. As CT is costly, associated with a high dose of radiation and
      not readily available, the ischiolateral method can be used for assessing the
      anteversion of the acetabular component. Cite this article: Bone Joint J 2017;99
      B:1006-11.

PMID- 28768777
TI  - Ceramic-on-ceramic bearing fractures in total hip arthroplasty: an analysis of
      data from the National Joint Registry.
AB  - AIMS: Ceramic-on-ceramic (CoC) bearings in total hip arthroplasty (THA) are
      commonly used, but concerns exist regarding ceramic fracture. This study aims to
      report the risk of revision for fracture of modern CoC bearings and identify
      factors that might influence this risk, using data from the National Joint
      Registry (NJR) for England, Wales, Northern Ireland and the Isle of Man. PATIENTS
      AND METHODS: We analysed data on 223 362 bearings from 111 681 primary CoC THAs
      and 182 linked revisions for bearing fracture recorded in the NJR. We used
      implant codes to identify ceramic bearing composition and generated Kaplan-Meier
      estimates for implant survivorship. Logistic regression analyses were performed
      for implant size and patient specific variables to determine any associated risks
      for revision. RESULTS: A total of 222 852 bearings (99.8%) were CeramTec Biolox
      products. Revisions for fracture were linked to seven of 79 442 (0.009%) Biolox
      Delta heads, 38 of 31 982 (0.119%) Biolox Forte heads, 101 of 80 170 (0.126%)
      Biolox Delta liners and 35 of 31 258 (0.112%) Biolox Forte liners. Regression
      analysis of implant size revealed smaller heads had significantly higher odds of
      fracture (chi-squared 68.0, p < 0.001). The highest fracture risk was observed in
      the 28 mm Biolox Forte subgroup (0.382%). There were no fractures in the 40 mm
      head group for either ceramic type. Liner thickness was not predictive of
      fracture (p = 0.67). Body mass index (BMI) was independently associated with
      revision for both head fractures (odds ratio (OR) 1.09 per unit increase, p =
      0.031) and liner fractures (OR 1.06 per unit increase, p = 0.006). CONCLUSIONS:
      We report the largest independent study of CoC bearing fractures to date. The
      risk of revision for CoC bearing fracture is very low but previous studies have
      underestimated this risk. There is good evidence that the latest generation of
      ceramic has greatly reduced the odds of head fracture but not of liner fracture.
      Small head size and high patient BMI are associated with an increased risk of
      ceramic bearing fracture. Cite this article: Bone Joint J 2017;99-B:1012-19.

PMID- 28768779
TI  - Cost effectiveness of patellofemoral versus total knee arthroplasty in younger
      patients.
AB  - AIMS: Patellofemoral arthroplasty (PFA) has experienced significant improvements
      in implant survivorship with second generation designs. This has renewed interest
      in PFA as an alternative to total knee arthroplasty (TKA) for younger active
      patients with isolated patellofemoral osteoarthritis (PF OA). We analysed the
      cost-effectiveness of PFA versus TKA for the management of isolated PF OA in the
      United States-based population. PATIENTS AND METHODS: We used a Markov transition
      state model to compare cost-effectiveness between PFA and TKA. Simulated patients
      were aged 60 (base case) and 50 years. Lifetime costs (2015 United States
      dollars), quality-adjusted life year (QALY) gains and incremental cost
      effectiveness ratio (ICER) were calculated from a healthcare payer perspective.
      Annual rates of revision were derived from the National Joint Registry for
      England, Wales, Northern Ireland and the Isle of Man. Deterministic and
      probabilistic sensitivity analysis was performed for all parameters against a $50
      000/QALY willingness to pay. RESULTS: PFA was more expensive ($49 811 versus $46
      632) but more effective (14.3 QALYs versus 13.3 QALYs) over a lifetime horizon.
      The ICER associated with the additional effectiveness of PFA was $3097. The model
      was mainly sensitive to utility values, with PFA remaining cost-effective when
      its utility exceeded that of TKA by at least 1.0%. PFA provided incremental
      benefits at no increased cost when annual rates of revision decreased by 24.5%.
      CONCLUSIONS: Recent improvements in rates of implant of survival have made PFA an
      economically beneficial joint-preserving procedure in younger patients, delaying
      TKA until implant failure or tibiofemoral OA progression. The present study
      quantified the minimum required marginal benefit for PFA to be cost-effective
      compared with TKA and identified survivorship targets for PFA to become both less
      expensive and more effective. These benchmarks might be used to assess clinical
      outcomes of PFA from an economic standpoint within the United States healthcare
      system. Cite this article: Bone Joint J 2017;99-B:1028-36.

PMID- 28768778
TI  - Which factors influence the rate of failure following metal-on-metal hip
      arthroplasty revision surgery performed for adverse reactions to metal debris? an
      analysis from the National Joint Registry for England and Wales.
AB  - AIMS: To determine the outcomes following revision surgery of metal-on-metal hip
      arthroplasties (MoMHA) performed for adverse reactions to metal debris (ARMD),
      and to identify factors predictive of re-revision. PATIENTS AND METHODS: We
      performed a retrospective observational study using National Joint Registry (NJR)
      data on 2535 MoMHAs undergoing revision surgery for ARMD between 2008 and 2014.
      The outcomes studied following revision were intra-operative complications,
      mortality and re-revision surgery. Predictors of re-revision were identified
      using competing-risk regression modelling. RESULTS: Intra-operative complications
      occurred in 40 revisions (1.6%). The cumulative five-year patient survival rate
      was 95.9% (95% confidence intervals (CI) 92.3 to 97.8). Re-revision surgery was
      performed in 192 hips (7.6%). The cumulative five-year implant survival rate was
      89.5% (95% CI 87.3 to 91.3). Predictors of re-revision were high body mass index
      at revision (subhazard ratio (SHR) 1.06 per kg/m2 increase, 95% CI 1.02 to 1.09),
      modular component only revisions (head and liner with or without taper adapter;
      SHR 2.01, 95% CI 1.19 to 3.38), ceramic-on-ceramic revision bearings (SHR 1.86,
      95% CI 1.23 to 2.80), and acetabular bone grafting (SHR 2.10, 95% CI 1.43 to
      3.07). These four factors remained predictive of re-revision when the missing
      data were imputed. CONCLUSION: The short-term risk of re-revision following MoMHA
      revision surgery performed for ARMD was comparable with that reported in the NJR
      following all-cause non-MoMHA revision surgery. However, the factors predictive
      of re-revision included those which could be modified by the surgeon, suggesting
      that rates of failure following ARMD revision may be reduced further. Cite this
      article: Bone Joint J 2017;99-B:1020-7.

PMID- 28768780
TI  - Activity levels and return to work following total knee arthroplasty in patients
      under 65 years of age.
AB  - AIMS: Little is known about employment following total knee arthroplasty (TKA).
      This study aims to identify factors which predict return to work following TKA in
      patients of working age in the United Kingdom. PATIENTS & METHODS: We
      prospectively assessed 289 patients (289 TKAs) aged <= 65 years who underwent TKA
      between 2010 and 2013. There were 148 women. The following were recorded pre
      operatively: age, gender, body mass index, social deprivation, comorbidities,
      indication for surgery, work status and nature of employment, activity level as
      assessed by the University of California, Los Angeles (UCLA) activity score and
      Oxford Knee Score (OKS). The intention of patients to return to work or to retire
      was not assessed pre-operatively. At a mean of 3.4 years (2 to 4) post
      operatively, the return to work status, OKS, the EuroQol-5 dimensions (EQ-5D)
      score, UCLA activity score and Work, Osteoarthritis and joint-Replacement (WORQ)
      score were obtained. Univariate and multivariate analyses were performed.
      RESULTS: Of 261 patients (90%) who were working before TKA, 105 (40%) returned to
      any job, including 89 (34%) who returned to the same job at a mean of 13.5 weeks
      (2 to 104) post-operatively. A total of 108 (41%) retired following TKA and 18
      remained on welfare. Patients not working before the operation did not return to
      work. Median UCLA scores improved in 125 patients (58%) from 4 (mild activity) to
      6 (moderate activity) (p < 0.001). Significant (p < 0.05) factors which were
      predictive of return to any work included age, heavy or moderate manual work,
      better post-operative UCLA, OKS and EQ-5D general health scores. Significant
      predictive factors of return to the same work included age, heavy or moderate
      manual work and post-operative OKS. Multivariate analysis confirmed heavy or
      moderate manual work and age to independently predict a return to either any or
      the same work. All patients aged < 50 years who were working pre-operatively
      returned to any work as did 60% of those aged between 50 and 54 years, 50% of
      those aged between 55 and 59 years and 24% those aged between 60 and 65 years.
      CONCLUSION: If working pre-operatively, patients aged < 50 years invariably
      returned to work following TKA, but only half of those aged between 50 to 60
      years returned. High post-operative activity levels and patient reported outcome
      measures do not predict return to work following TKA. Cite this article: Bone
      Joint J 2017;99-B:1037-46.

PMID- 28768781
TI  - Usefulness of an accelerometer-based portable navigation system in total knee
      arthroplasty.
AB  - AIMS: The aim of this study was to evaluate the effects of using a portable,
      accelerometer-based surgical navigation system (KneeAlign2) in total knee
      arthroplasty (TKA) on the alignment of the femoral component, and blood loss.
      PATIENTS AND METHODS: A total of 241 consecutive patients with primary
      osteoarthritis of the knee were enrolled in this prospective, randomised
      controlled study. There were 207 women and 34 men. The mean age of the patients
      was 74.0 years (57 to 89). The KneeAlign2 system was used for distal femoral
      resection in 121 patients (KA2 group) and a conventional intramedullary femoral
      guide was used in 120 patients (IM group). RESULTS: One patient (0.8%) in the KA2
      group and 19 in the IM group had an alignment which was > 3 degrees  away from
      the neutral mechanical axis (p < 0.01). The mean deviation from neutral alignment
      was 1.01 degrees  (standard deviation (sd) 1.0 degrees ) in the KA2 group and
      1.93 degrees  (sd 1.7 degrees ) in the IM group (p < 0.01). Blood loss was
      significantly less in the KA2 group compared with the IM group (784 ml (sd 357)
      versus 1071 ml (sd 310), p < 0.001). CONCLUSION: The KneeAlign2 system provides a
      technically straightforward method for identifying the femoral head and
      performing an accurate distal femoral resection at TKA with significantly less
      blood loss compared with a conventional intramedullary guide. Cite this article:
      Bone Joint J 2017;99-B:1047-52.

PMID- 28768782
TI  - Anterior cruciate ligament reconstruction in skeletally immature patients : a
      systematic review.
AB  - AIMS: Different methods of anterior cruciate ligament (ACL) reconstruction have
      been described for skeletally immature patients before closure of the growth
      plates. However, the outcome and complications following this treatment remain
      unclear. The aim of this systematic review was to analyse the outcome and
      complications of different techniques which may be used for reconstruction of the
      ACL in these patients. MATERIALS AND METHODS: We performed a systematic review of
      the literature according to the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses guidelines. This involved a comprehensive search of PubMed,
      Medline, CINAHL, Cochrane, Embase and Google Scholar databases using the
      following combinations of keywords, "knee", "anterior cruciate ligament",
      "reconstruction", "injury", "children", "adolescent", "skeletally immature",
      "open physis" and "surgery". RESULTS: A total of 53 studies met the inclusion
      criteria and were included for analysis. The overall rate of disturbance of
      growth after ACL reconstruction was 2.6%, with no statistical difference between
      transphyseal and physeal-sparing techniques. Physeal-sparing techniques had a
      lower rate of post-operative complications compared with transphyseal techniques
      (p = 0.0045). Outcomes assessed were Lysholm score, International Knee
      Documentation Committee (IKDC) score, the IKDC grade, the Tegner score and the KT
      1000. Both techniques had similar clinical outcomes. CONCLUSIONS: This review
      reveals low rates of disturbance of growth after ACL reconstruction in skeletally
      immature patients. Although limited, the available evidence did not support any
      particular surgical technique when considering disturbance of growth or clinical
      outcome. Further randomised controlled trials are needed to investigate the
      efficacy of differing surgical techniques on outcomes in skeletally immature
      patients. Cite this article: Bone Joint J 2017;99-B:1053-60.

PMID- 28768783
TI  - The effect of operating lights on laminar flow: an experimental study using
      neutrally buoyant helium bubbles.
AB  - AIMS: The interaction between surgical lighting and laminar airflow is poorly
      understood. We undertook an experiment to identify any effect contemporary
      surgical lights have on laminar flow and recommend practical strategies to limit
      any negative effects. MATERIALS AND METHODS: Neutrally buoyant bubbles were
      introduced into the surgical field of a simulated setup for a routine total knee
      arthroplasty in a laminar flow theatre. Patterns of airflow were observed and the
      number of bubbles remaining above the surgical field over time identified. Five
      different lighting configurations were assessed. Data were analysed using simple
      linear regression after logarithmic transformation. RESULTS: In the absence of
      surgical lights, laminar airflow was observed, bubbles were cleared rapidly and
      did not accumulate. If lights were placed above the surgical field laminar
      airflow was abolished and bubbles rose from the surgical field to the lights then
      circulated back to the surgical field. The value of the decay parameter (slope)
      of the two setups differed significantly; no light (b = -1.589) versus one light
      (b = -0.1273, p < 0.001). Two lights touching (b = -0.1191) above the surgical
      field had a similar effect to that of a single light (p = 0. 2719). Two lights
      positioned by arms outstretched had a similar effect (b = -0.1204) to two lights
      touching (p = 0.998) and one light (p = 0.444). When lights were separated widely
      (160 cm), laminar airflow was observed but the rate of clearance of the bubbles
      remained slower (b = -1.1165) than with no lights present (p = 0.004).
      CONCLUSION: Surgical lights have a significantly negative effect on laminar
      airflow. Lights should be positioned as far away as practicable from the surgical
      field to limit this effect. Cite this article: Bone Joint J 2017;99-B:1061-6.

PMID- 28768784
TI  - The colonisation of the glenohumeral joint by Propionibacterium acnes is not
      associated with frozen shoulder but is more likely to occur after an injection
      into the joint.
AB  - AIMS: Our aim was to investigate the prevalence of Propionibacterium (P.) acnes
      in the subcutaneous fat and capsule of patients undergoing shoulder surgery for
      frozen shoulder or instability. PATIENTS AND METHODS: A total of 46 patients
      undergoing either an arthroscopic capsular release or stabilisation had biopsies
      taken from the subcutaneous fat and capsule of the shoulder at the time of
      surgery. These samples were sent for culture in enrichment, and also for Nucleic
      Acid Amplification testing. The prevalence of P. acnes and other microbes was
      recorded. Fisher's exact test of binary variables was used to calculate the
      association with significance set at p < 0.05. Assessment of influence of
      independent variables including a pre-operative glenohumeral injection, fat
      colonisation and gender, was undertaken using binary linear regression. RESULTS:
      A total of 25 patients (53%) had P. acnes in one or more tissue samples and 35
      (74%) had other bacterial species. The same microbe was found in the subcutaneous
      fat and the capsule in 13 patients (28%). There was no statistically significant
      association between the surgical pathology and capsular colonisation with P.
      acnes (p = 0.18) or mixed identified bacterial species (p = 0.77). Male gender
      was significantly associated with an increased capsular colonisation of P. acnes
      (odds ratio (OR) 12.38, 95% confidence interval (CI) 1.43 to 106.77, p = 0.02). A
      pre-operative glenohumeral injection was significantly associated with capsular
      P. acnes colonisation (OR 5.63, 95% CI 1.07 to 29.61, p = 0.04. Positive fat
      colonisation with P. acnes was significantly associated with capsular P. acnes
      (OR 363, 95% CI 20.90 to 6304.19, p < 0.01). Regression models pseudo R2 found
      fat colonisation with P. acnes to explain 70% of the variance of the model.
      Patients who had a pre-operative glenohumeral injection who were found intra
      operatively to have fat colonisation with P. acnes had a statistically
      significant association with colonisation of their capsule with P. acnes (OR 165,
      95% CI 13.51 to 2015.24, p < 0.01). CONCLUSION: These results show a
      statistically significant association between subcutaneous skin P. acnes culture
      and P. acnes capsular culture, especially when the patient has undergone a
      previous injection. The results refute the hypothesis that P. acnes causes frozen
      shoulder. Cite this article: Bone Joint J 2017;99-B:1067-72.

PMID- 28768786
TI  - Posterior spinal fusion for adolescent idiopathic scoliosis using a convex
      pedicle screw technique: a novel concept of deformity correction.
AB  - AIMS: We present the results of correcting a double or triple curve adolescent
      idiopathic scoliosis using a convex segmental pedicle screw technique. PATIENTS
      AND METHODS: We reviewed 191 patients with a mean age at surgery of 15 years (11
      to 23.3). Pedicle screws were placed at the convexity of each curve. Concave
      screws were inserted at one or two cephalad levels and two caudal levels. The
      mean operating time was 183 minutes (132 to 276) and the mean blood loss 0.22% of
      the total blood volume (0.08% to 0.4%). Multimodal monitoring remained stable
      throughout the operation. The mean hospital stay was 6.8 days (5 to 15). RESULTS:
      The mean post-operative follow-up was 5.8 years (2.5 to 9.5). There were no
      neurological complications, deep wound infection, obvious nonunion or need for
      revision surgery. Upper thoracic scoliosis was corrected by a mean 68.2% (38% to
      48%, p < 0.001). Main thoracic scoliosis was corrected by a mean 71% (43.5% to
      8.9%, p < 0.001). Lumbar scoliosis was corrected by a mean 72.3% (41% to 90%, p <
      0.001). No patient lost more than 3 degrees  of correction at follow-up. The
      thoracic kyphosis improved by 13.1 degrees  (-21 degrees  to 49 degrees , p <
      0.001); the lumbar lordosis remained unchanged (p = 0.58). Coronal imbalance was
      corrected by a mean 98% (0% to 100%, p < 0.001). Sagittal imbalance was corrected
      by a mean 96% (20% to 100%, p < 0.001). The Scoliosis Research Society Outcomes
      Questionnaire score improved from a mean 3.6 to 4.6 (2.4 to 4, p < 0.001);
      patient satisfaction was a mean 4.9 (4.8 to 5). CONCLUSIONS: This technique
      carries low neurological and vascular risks because the screws are placed in the
      pedicles of the convex side of the curve, away from the spinal cord, cauda equina
      and the aorta. A low implant density (pedicle screw density 1.2, when a density
      of 2 represents placement of pedicle screws bilaterally at every instrumented
      segment) achieved satisfactory correction of the scoliosis, an improved thoracic
      kyphosis and normal global sagittal balance. Both patient satisfaction and
      functional outcomes were excellent. Cite this article: Bone Joint J 2017;99
      B:1080-7.

PMID- 28768785
TI  - The effect of intravenous tranexamic acid on blood loss and early post-operative
      pain in total shoulder arthroplasty.
AB  - AIMS: The purpose of the present study was to evaluate the impact of intravenous
      tranexamic acid on the reduction of blood loss, transfusion rate, and early post
      operative clinical outcome in total shoulder arthroplasty. PATIENTS AND METHODS:
      A randomised, placebo-controlled trial which included 54 patients undergoing
      unilateral primary stemless anatomical or stemmed reverse total shoulder
      arthroplasty was undertaken. Patients received either 100 ml saline (placebo, n =
      27), or 100 ml saline together with 1000 mg of tranexamic acid (TXA, n = 27)
      intravenously prior to skin incision and during wound closure. Peri-operative
      blood loss via an intra-articular drain was recorded and total blood loss was
      calculated. The post-operative transfusion rate was documented. Assessment of
      early clinical parameters included the visual analogue scale for pain (VAS),
      documentation of haematoma formation and adverse events. RESULTS: Mean peri
      operative blood drainage (placebo: 170 ml versus TXA: 50 ml, p = 0.001) and
      calculated mean total blood loss (placebo: 1248.2 ml versus TXA: 871.0 ml, p =
      0.009) were significantly lower in the TXA group. No transfusions were necessary
      during the study period in either group. Mean VAS for pain significantly
      decreased from pre-operative (VAS 7) to the early post-operative period (VAS 1.7,
      p < 0.001). Significant differences regarding mean post-operative pain between
      placebo (VAS 2.0) and TXA (VAS 1.3) were detected (p = 0.05). The occurrence of
      haematomas was significantly more frequent in the placebo (59.3%, n = 16) than in
      the TXA group (25.9%, n = 6, p = 0.027). Whereas only mild haematomas developed
      in the TXA group, in the placebo group a total of 22.2% (n = 6) developed either
      moderate or severe haematomas. No adverse events associated with administration
      of TXA occurred. CONCLUSION: Intravenous administration of TXA successfully
      reduced mean peri-operative blood drainage, total estimated blood loss, pain
      during the first post-operative days, and haematoma formation in total shoulder
      arthroplasty. Cite this article: Bone Joint J 2017;99-B:1073-9.

PMID- 28768787
TI  - Factors affecting the rate of surgical site infection in patients after
      hemiarthroplasty of the hip following a fracture of the neck of the femur.
AB  - AIMS: Surgical site infection can be a devastating complication of
      hemiarthroplasty of the hip, when performed in elderly patients with a displaced
      fracture of the femoral neck. It results in a prolonged stay in hospital, a poor
      outcome and increased costs. Many studies have identified risk and prognostic
      factors for deep infection. However, most have combined the rates of infection
      following total hip arthroplasty and internal fixation as well as
      hemiarthroplasty, despite the fact that they are different entities. The aim of
      this study was to clarify the risk and prognostic factors causing deep infection
      after hemiarthroplasty alone. PATIENTS AND METHODS: Data were extracted from a
      prospective hip fracture database and completed by retrospective review of the
      hospital records. A total of 916 patients undergoing a hemiarthroplasty in two
      level II trauma teaching hospitals between 01 January 2011 and 01 May 2016 were
      included. We analysed the potential peri-operative risk factors with univariable
      and multivariable logistic regression analysis. RESULTS: A total of 92 patients
      (10%) had a surgical site infection, and 44 (4.9%) developed a deep infection.
      After univariable analyses, the multivariable model showed that the level of
      experience of the surgeon measured by the number of hemiarthroplasties performed
      per year was a significant prognostic factor (odds ratio (OR) 0.93, p = 0.042)
      for the development of an infection. Secondly, the development of a haematoma (OR
      9.6, p < 0.001), a re-operation (OR 4.7, p = 0.004) and an operating time of < 45
      mins (OR 5.1, p = 0.002) or > 90 mins (OR 2.7, p = 0.034) were also significant
      factors. CONCLUSION: There was a significant association between the experience
      of the surgeon and the rate of deep infection. Secondly, a haematoma, a re
      operation and both shorter and longer operating times were associated with an
      increased risk of deep infection after hemiarthroplasty. No association was found
      between deep infection and the anatomical approach, the time when surgery was
      undertaken and the use of a drain. Cite this article: Bone Joint J 2017;99-B:1088
      94.

PMID- 28768788
TI  - Plate fixation versus intramedullary nailing of completely displaced midshaft
      fractures of the clavicle: a prospective randomised controlled trial.
AB  - AIMS: This is a prospective randomised controlled trial comparing the functional
      outcomes of plate fixation and elastic stable intramedullary nailing (ESIN) of
      completely displaced mid-shaft fractures of the clavicle in the active adult
      population. PATIENTS AND METHODS: We prospectively recruited 123 patients and
      randomised them to either plate fixation or ESIN. Patients completed the Quick
      Disabilities of the Arm, Shoulder and Hand (DASH) score at one to six weeks post
      operatively. They were followed up at six weeks, three and six months and one
      year with radiographs, and their clinical outcome was assessed using both the
      DASH and the Constant Score. RESULTS: Plate fixation provided a faster functional
      recovery during the first six months compared with ESIN, but there was no
      difference after one year. The duration of surgery was shorter for ESIN (mean
      53.4 minutes, 22 to 120) than for plate fixation (mean 69.7 minutes, 35 to 106, p
      < 0.001). The recovery after ESIN was slower with increasing fracture comminution
      and with open reduction (p < 0.05). CONCLUSION: Both methods return the patients
      to their pre-injury functional levels, but plate fixation has a faster recovery
      period in comminuted fractures than ESIN. ESIN has a shorter operative time and
      lower infection and implant rates of failure when using 2.5 mm nails or wider,
      suggesting that this is the preferred method in mid-shaft fractures with no
      comminution, whereas plate fixation is the superior method in comminuted
      fractures. Cite this article: Bone Joint J 2017;99-B:1095-1101.

PMID- 28768789
TI  - A case control study to determine the association between Perthes' disease and
      the recalled use of tobacco during pregnancy, and biological markers of current
      tobacco smoke exposure.
AB  - AIMS: It is well established that there is a strong association between Perthes'
      disease and worsening socioeconomic deprivation. It has been suggested that the
      primary determinant driving this association is exposure to tobacco smoke. This
      study aimed to examine this hypothesis. PATIENTS AND METHODS: A hospital case
      control study (n = 149/146) examined the association between tobacco smoke
      exposure and Perthes' disease, adjusting for area-level socioeconomic
      deprivation. Tobacco smoke exposure was assessed by parental questionnaire of
      smoking habits during pregnancy, and by quantitative assay of current exposure
      using the urinary cotinine-creatinine ratio, which is a widely used and validated
      measure of tobacco smoke exposure. RESULTS: The odds of Perthes' disease
      significantly increased with reported in utero exposure after adjustment for
      socioeconomic deprivation (maternal smoking odds ratio (OR) 2.06, 95% confidence
      interval (CI) 1.17 to 3.63; paternal smoking OR 2.09, 95% CI 1.26 to 3.46). The
      cotinine-creatinine ratio was significantly greater in cases, OR 1.63 (95% CI
      1.09 to 2.43), suggesting a greater 'dose' of current tobacco exposure.
      CONCLUSION: An association exists between tobacco smoke exposure and Perthes'
      disease but we remain unable to disentangle the association with socioeconomic
      deprivation. Cite this article: Bone Joint J 2017;99-B:1102-8.

PMID- 28768790
TI  - Quantification of the ossification of the lateral cuneiform in the feet of young
      children with unilateral congenital talipes equinovarus.
AB  - AIMS: After the initial correction of congenital talipes equinovarus (CTEV) using
      the Ponseti method, a subsequent dynamic deformity is often managed by transfer
      of the tendon of tibialis anterior (TATT) to the lateral cuneiform. Many surgeons
      believe the lateral cuneiform should be ossified before surgery is undertaken.
      This study quantifies the ossification process of the lateral cuneiform in
      children with CTEV between one and three years of age. PATIENTS AND METHODS: The
      length, width and height of the lateral cuneiform were measured in 43 consecutive
      patients with unilateral CTEV who had been treated using the Ponseti method.
      Measurements were taken by two independent observers on standardised
      anteroposterior and lateral radiographs of both feet taken at one, two and three
      years of age. RESULTS: All dimensions of the lateral cuneiform on the affected
      side increased annually but remained smaller than the corresponding dimensions of
      the unaffected foot (p < 0.01). The lateral cuneiform resembled a 9 mm cube at
      two years and an 11 mm cube at three years. CONCLUSION: At one and two years, the
      ossification centre of the lateral cuneiform may not be large enough to
      accommodate a drill hole for tendon transfer. However, by three years, it has
      undergone sufficient ossification to do so. Cite this article: Bone Joint J
      2017;99-B:1109-14.

PMID- 28768792
TI  - Regulation of Synaptic Amyloid-beta Generation through BACE1 Retrograde Transport
      in a Mouse Model of Alzheimer's Disease.

PMID- 28768791
TI  - The correlation between Salter's criteria for avascular necrosis of the femoral
      head and Kalamchi's prognostic classification following the treatment of
      developmental dysplasia of the hip.
AB  - AIMS: The aim of this study was to evaluate the correlation between Salter's
      criteria and Kalamchi's classification of avascular necrosis in patients treated
      for developmental dysphasia of the hip (DDH). PATIENTS AND METHODS: The study
      involved a retrospective analysis of 123 patients (123 hips) with DDH treated by
      operative and non-operative reduction before the age of two years, with a minimum
      follow-up of ten years. Salter's criteria (S1 to S4) were determined from
      radiographs obtained at one to two years post-reduction, whilst the Kalamchi
      grade was determined from radiographs obtained at ten or more years of age. Early
      post-reduction radiographs were also used to evaluate the centre-head distance
      discrepancy (CHDD) and the occurrence of a dome-shaped deformity of the proximal
      femoral metaphysis (D-shaped metaphysis). The prognosis was described as good
      (Kalamchi grade K0 or KI), fair (Kalamchi grade KII) or poor (Kalamchi grade KIII
      or KIV) for analysis and correlation with the early Salter criteria, CHDD and D
      shaped metaphysis. RESULTS: S1 and S2 criteria were predictive of a poor
      prognosis. The outcome following S3, S4 and S3 + S4 varied; 18 (40%) had a good
      prognosis, 17 (38%) a fair prognosis and ten (22%) a poor prognosis. A CHDD >=
      10% and a D-shaped metaphysis were also predictive of a poor prognosis.
      CONCLUSION: The Salter criteria were predictive of the Kalamchi grade of
      avascular necrosis in patients with DDH aged ten or more years after reduction of
      the hip. Cite this article: Bone Joint J 2017;99-B:1115-20.

PMID- 28768793
TI  - Sleepy Circuits in Vigilant Mice? A Slow Cortical Oscillation Occurring during
      Multiple Arousal States.

PMID- 28768794
TI  - Embryonic stem cell derived germ cells induce spermatogenesis after
      transplantation into the testes of an adult mouse azoospermia model.
AB  - The present study aimed to: (i) identify the exogenous factors that allow in
      vitro differentiation of mouse spermatogonial stem cells (SSCs) from embryonic
      stem cells (ESCs); (ii) evaluate the effects of Sertoli cells in SSC enrichment;
      and (iii) assess the success of transplantation using in vitro differentiated
      SSCs in a mouse busulfan-treated azoospermia model. A 1-day-old embryoid body
      (EB) received 5 ng/ml of bone morphogenetic protein 4 (BMP4) for 4 days, 3 uM
      retinoic acid (RA) in a SIM mouse embryo-derived thioguanine and ouabain
      resistant (STO) co-culture system for 7 days, and was subsequently co-cultured
      for 2 days with Sertoli cells in the presence or absence of a leukaemia
      inhibitory factor (LIF), basic fibroblast growth factor (bFGF) and RA
      composition, and in the presence of these factors in simple culture medium.
      Higher viability, proliferation and germ cell gene expression were seen in the
      presence of the LIF, bFGF and RA composition, on top of Sertoli cells.
      Immunocytochemistry results showed higher CDH1 expression in this group. Sertoli
      co-culture had no effects on SSC proliferation. Eight weeks after
      transplantation, injected cells were observed at the base of the seminiferous
      tubules and in the recipient testes. The number of spermatogonia and the mass of
      the testes were higher in transplanted testes relative to the control group. It
      seems that transplantation of these cells can be useful in infertility treatment.

PMID- 28768795
TI  - Possible co-option of engrailed during brachiopod and mollusc shell development.
AB  - In molluscs, two homeobox genes, engrailed (en) and distal-less (dlx), are
      transcription factors that are expressed in correlation with shell development.
      They are expressed in the regions between shell-forming and non-shell-forming
      cells, likely defining the boundaries of shell-forming fields. Here we
      investigate the expression of two transcription factors in the brachiopod Lingula
      anatina We find that en is expressed in larval mantle lobes, whereas dlx is
      expressed in larval tentacles. We also demonstrate that the embryonic shell
      marker mantle peroxidase (mpox) is specifically expressed in mantle lobes. Our
      results suggest that en and mpox are possibly involved in brachiopod embryonic
      shell development. We discuss the evolutionary developmental origin of
      lophotrochozoan biomineralization through independent gene co-option.

PMID- 28768796
TI  - Feeding the enemy: loss of nectar and nectaries to herbivores reduces tepal
      damage and increases pollinator attraction in Iris bulleyana.
AB  - Floral nectar usually functions as a pollinator reward, yet it may also attract
      herbivores. However, the effects of herbivore consumption of nectar or nectaries
      on pollination have rarely been tested. We investigated Iris bulleyana, an alpine
      plant that has showy tepals and abundant nectar, in the Hengduan Mountains of SW
      China. In this region, flowers are visited mainly by pollen-collecting
      pollinators and nectarivorous herbivores. We tested the hypothesis that, in I.
      bulleyana, sacrificing nectar and nectaries to herbivores protects tepals and
      thus enhances pollinator attraction. We compared rates of pollination and
      herbivory on different floral tissues in plants with flowers protected from
      nectar and nectary consumption with rates in unprotected control plants. We found
      that nectar and nectaries suffered more herbivore damage than did tepals in
      natural conditions. However, the amount of tepal damage was significantly greater
      in the flowers with protected nectaries than in the controls; this resulted in
      significant differences in pollinator visitation rates. These results provide the
      first evidence that floral nectar and nectaries may be 'sacrificed' to
      herbivores, leading to reduced damage to other floral tissues that are more
      important for reproduction.

PMID- 28768797
TI  - Has snake fang evolution lost its bite? New insights from a structural mechanics
      viewpoint.
AB  - Venomous snakes-the pinnacle of snake evolution-are characterized by their
      possession of venom-conducting fangs ranging from grooved phenotypes
      characterizing multiple lineages of rear-fanged taxa to tubular phenotypes
      present in elapids, viperids and atractaspidines. Despite extensive research,
      controversy still exists on the selective pressures involved in fang phenotype
      diversification. Here, we test the hypothesis that larger fangs and consequently
      a shift to an anterior position in the maxilla evolved to compensate for the
      costs of structural changes, i.e. higher stress upon impact in tubular fangs
      compared to grooved fangs. Direct voxel-based stress simulations conducted on
      high-resolution uCT scans, analysed within a phylogenetic framework, showed no
      differences in stress distribution between the three fang phenotypes, despite
      differences in (relative) fang length. These findings suggest that additional
      compensatory mechanisms are responsible for the biomechanical optimization and
      that fang length might instead be related to differential striking behaviour
      strategies.

PMID- 28768798
TI  - Unlocking the Keys to Site Activation and Recruitment Success in a Randomized
      Controlled Trial.

PMID- 28768799
TI  - MicroRNA Changes in Cerebrospinal Fluid After Subarachnoid Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) accounts for a major part
      of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH).
      MicroRNAs (miRNAs) are pathophysiologically involved in acute cerebral ischemia.
      This study compared miRNA profiles in cerebrospinal fluid from neurologically
      healthy patients, as well as SAH patients with and without subsequent development
      of DCI. METHODS: In a prospective case-control study of SAH patients treated with
      external ventricular drainage and neurologically healthy patients, miRNA profiles
      in cerebrospinal fluid were screened and validated using 2 different high
      throughput real-time quantification polymerase chain reaction techniques. The
      occurrence of DCI was documented in patient charts and subsequently reviewed
      independently by 2 physicians. RESULTS: MiRNA profiles from 27 SAH patients and
      10 neurologically healthy patients passed quality control. In the validation, 66
      miRNAs showed a relative increase in cerebrospinal fluid from SAH patients
      compared with neurologically healthy patients (P<0.001); 2 (miR-21 and miR-221)
      showed a relative increase in SAH patients with DCI compared with those without
      (P<0.05) in both the screening and validation. CONCLUSIONS: SAH is associated
      with marked changes in the cerebrospinal fluid miRNA profile. These changes could
      be associated to the development of DCI. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01791257.

PMID- 28768801
TI  - Pinning allergies on pathogenic TH2 cells.
AB  - A new proinflammatory subtype of antigen-specific TH2 cell that expresses CD161
      emerges as the pathogenic cell type in allergic disease and is deleted during
      allergen-specific immunotherapy (Wambre et al, this issue).

PMID- 28768800
TI  - Factors Associated With Time to Site Activation, Randomization, and Enrollment
      Performance in a Stroke Prevention Trial.
AB  - BACKGROUND AND PURPOSE: Multicenter clinical trials attempt to select sites that
      can move rapidly to randomization and enroll sufficient numbers of patients.
      However, there are few assessments of the success of site selection. METHODS: In
      the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic
      Carotid Stenosis Trials), we assess factors associated with the time between site
      selection and authorization to randomize, the time between authorization to
      randomize and the first randomization, and the average number of randomizations
      per site per month. Potential factors included characteristics of the site,
      specialty of the principal investigator, and site type. RESULTS: For 147 sites,
      the median time between site selection to authorization to randomize was 9.9
      months (interquartile range, 7.7, 12.4), and factors associated with early site
      activation were not identified. The median time between authorization to
      randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5).
      Sites with authorization to randomize in only the carotid endarterectomy study
      were slower to randomize, and other factors examined were not significantly
      associated with time-to-randomization. The recruitment rate was 0.26 (95%
      confidence interval, 0.23-0.28) patients per site per month. By univariate
      analysis, factors associated with faster recruitment were authorization to
      randomize in both trials, principal investigator specialties of interventional
      radiology and cardiology, pre-trial reported performance >50 carotid angioplasty
      and stenting procedures per year, status in the top half of recruitment in the
      CREST trial, and classification as a private health facility. Participation in
      StrokeNet was associated with slower recruitment as compared with the non
      StrokeNet sites. CONCLUSIONS: Overall, selection of sites with high enrollment
      rates will likely require customization to align the sites selected to the factor
      under study in the trial. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT02089217.

PMID- 28768802
TI  - Comment on "Using geospatial mapping to design HIV elimination strategies for sub
      Saharan Africa".
AB  - A recent study showed how geospatial mapping can be used to improve Lesotho's HIV
      treatment program to achieve the 90-90-90 targets set by the United Nations but
      incorrectly describes "treatment as prevention" as the UN's strategy for a
      successful national AIDS response.

PMID- 28768803
TI  - Modulation of prefrontal cortex excitation/inhibition balance rescues social
      behavior in CNTNAP2-deficient mice.
AB  - Alterations in the balance between neuronal excitation and inhibition (E:I
      balance) have been implicated in the neural circuit activity-based processes that
      contribute to autism phenotypes. We investigated whether acutely reducing E:I
      balance in mouse brain could correct deficits in social behavior. We used mice
      lacking the CNTNAP2 gene, which has been implicated in autism, and achieved a
      temporally precise reduction in E:I balance in the medial prefrontal cortex
      (mPFC) either by optogenetically increasing the excitability of inhibitory
      parvalbumin (PV) neurons or decreasing the excitability of excitatory pyramidal
      neurons. Surprisingly, both of these distinct, real-time, and reversible
      optogenetic modulations acutely rescued deficits in social behavior and
      hyperactivity in adult mice lacking CNTNAP2 Using fiber photometry, we discovered
      that native mPFC PV neuronal activity differed between CNTNAP2 knockout and wild
      type mice. During social interactions with other mice, PV neuron activity
      increased in wild-type mice compared to interactions with a novel object, whereas
      this difference was not observed in CNTNAP2 knockout mice. Together, these
      results suggest that real-time modulation of E:I balance in the mouse prefrontal
      cortex can rescue social behavior deficits reminiscent of autism phenotypes.

PMID- 28768805
TI  - Response to comment on "Using geospatial mapping to design HIV elimination
      strategies for sub-Saharan Africa".
AB  - Detailed geospatial mapping of a generalized HIV epidemic in sub-Saharan Africa
      shows that implementing the Joint United Nations Programme on HIV/AIDS (UNAIDS)
      90-90-90 strategy could potentially exacerbate urban-rural health care
      disparities.

PMID- 28768804
TI  - Synergistic action of the MCL-1 inhibitor S63845 with current therapies in
      preclinical models of triple-negative and HER2-amplified breast cancer.
AB  - The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL
      2 family, represents a potential breakthrough in cancer therapy. Targeting the
      prosurvival member MCL-1 has been an area of intense interest because it is
      frequently deregulated in cancer. In breast cancer, MCL-1 is often amplified, and
      high expression predicts poor patient outcome. We tested the MCL-1 inhibitor
      S63845 in breast cancer cell lines and patient-derived xenografts with high
      expression of MCL-1. S63845 displayed synergistic activity with docetaxel in
      triple-negative breast cancer and with trastuzumab or lapatinib in HER2-amplified
      breast cancer. Using S63845-resistant cells combined with CRISPR (clustered
      regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated 9)
      technology, we identified deletion of BAK and up-regulation of prosurvival
      proteins as potential mechanisms that confer resistance to S63845 in breast
      cancer. Collectively, our findings provide a strong rationale for the clinical
      evaluation of MCL-1 inhibitors in breast cancer.

PMID- 28768806
TI  - A phenotypically and functionally distinct human TH2 cell subpopulation is
      associated with allergic disorders.
AB  - Allergen-specific type 2 helper T (TH2) cells play a central role in initiating
      and orchestrating the allergic and asthmatic inflammatory response pathways. One
      major factor limiting the use of such atopic disease-causing T cells as both
      therapeutic targets and clinically useful biomarkers is the lack of an accepted
      methodology to identify and differentiate these cells from overall nonpathogenic
      TH2 cell types. We have described a subset of human memory TH2 cells confined to
      atopic individuals that includes all allergen-specific TH2 cells. These cells are
      terminally differentiated CD4+ T cells (CD27- and CD45RB-) characterized by
      coexpression of CRTH2, CD49d, and CD161 and exhibit numerous functional
      attributes distinct from conventional TH2 cells. Hence, we have denoted these
      cells with this stable allergic disease-related phenotype as the TH2A cell
      subset. Transcriptome analysis further revealed a distinct pathway in the
      initiation of pathogenic responses to allergen, and elimination of these cells is
      indicative of clinical responses induced by immunotherapy. Together, these
      findings identify a human TH2 cell signature in allergic diseases that could be
      used for response-monitoring and designing appropriate immunomodulatory
      strategies.

PMID- 28768808
TI  - Transmembrane allosteric energetics characterization for strong coupling between
      proton and potassium ion binding in the KcsA channel.
AB  - The slow spontaneous inactivation of potassium channels exhibits classic
      signatures of transmembrane allostery. A variety of data support a model in which
      the loss of K+ ions from the selectivity filter is a major factor in promoting
      inactivation, which defeats transmission, and is allosterically coupled to
      protonation of key channel activation residues, more than 30 A from the K+ ion
      binding site. We show that proton binding at the intracellular pH sensor perturbs
      the potassium affinity at the extracellular selectivity filter by more than three
      orders of magnitude for the full-length wild-type KcsA, a pH-gated bacterial
      channel, in membrane bilayers. Studies of F103 in the hinge of the inner helix
      suggest an important role for its bulky sidechain in the allosteric mechanism; we
      show that the energetic strength of coupling of the gates is strongly altered
      when this residue is mutated to alanine. These results provide quantitative site
      specific measurements of allostery in a bilayer environment, and highlight the
      power of describing ion channel gating through the lens of allosteric coupling.

PMID- 28768807
TI  - FolamiRs: Ligand-targeted, vehicle-free delivery of microRNAs for the treatment
      of cancer.
AB  - MicroRNAs are small RNAs that negatively regulate gene expression
      posttranscriptionally. Because changes in microRNA expression can promote or
      maintain disease states, microRNA-based therapeutics are being evaluated
      extensively. Unfortunately, the therapeutic potential of microRNA replacement is
      limited by deficient delivery vehicles. In this work, microRNAs are delivered in
      the absence of a protective vehicle. The method relies on direct attachment of
      microRNAs to folate (FolamiR), which mediates delivery of the conjugated microRNA
      into cells that overexpress the folate receptor. We show that the tumor
      suppressive FolamiR, FolamiR-34a, is quickly taken up both by triple-negative
      breast cancer cells in vitro and in vivo and by tumors in an autochthonous model
      of lung cancer and slows their progression. This method delivers microRNAs
      directly to tumors in vivo without the use of toxic vehicles, representing an
      advance in the development of nontoxic, cancer-targeted therapeutics.

PMID- 28768809
TI  - 2-Hydroxyisobutyrylation on histone H4K8 is regulated by glucose homeostasis in
      Saccharomyces cerevisiae.
AB  - New types of modifications of histones keep emerging. Recently, histone H4K8 2
      hydroxyisobutyrylation (H4K8hib) was identified as an evolutionarily conserved
      modification. However, how this modification is regulated within a cell is still
      elusive, and the enzymes adding and removing 2-hydroxyisobutyrylation have not
      been found. Here, we report that the amount of H4K8hib fluctuates in response to
      the availability of carbon source in Saccharomyces cerevisiae and that low
      glucose conditions lead to diminished modification. The removal of the 2
      hydroxyisobutyryl group from H4K8 is mediated by the histone lysine deacetylase
      Rpd3p and Hos3p in vivo. In addition, eliminating modifications at this site by
      alanine substitution alters transcription in carbon transport/metabolism genes
      and results in a reduced chronological life span (CLS). Furthermore, consistent
      with the glucose-responsive H4K8hib regulation, proteomic analysis revealed that
      a large set of proteins involved in glycolysis/gluconeogenesis are modified by
      lysine 2-hydroxyisobutyrylation. Cumulatively, these results established a
      functional and regulatory network among Khib, glucose metabolism, and CLS.

PMID- 28768810
TI  - Mouse macrophages show different requirements for phosphatidylserine receptor
      Tim4 in efferocytosis.
AB  - Protein S (ProS) and growth arrest-specific 6 (Gas6) bind to phosphatidylserine
      (PtdSer) and induce efferocytosis upon binding TAM-family receptors (Tyro3, Axl,
      and Mer). Here, we produced mouse ProS, Gas6, and TAM-receptor extracellular
      region fused to IgG fragment crystallizable region in HEK293T cells. ProS and
      Gas6 bound Ca2+ dependently to PtdSer (Kd 20-40 nM), Mer, and Tyro3 (Kd 15-50
      nM). Gas6 bound Axl strongly (Kd < 1.0 nM), but ProS did not bind Axl. Using NIH
      3T3-based cell lines expressing a single TAM receptor, we showed that TAM
      mediated efferocytosis was determined by the receptor-binding ability of ProS and
      Gas6. Tim4 is a membrane protein that strongly binds PtdSer. Tim4 alone did not
      support efferocytosis, but enhanced TAM-dependent efferocytosis. Resident
      peritoneal macrophages, Kupffer cells, and CD169+ skin macrophages required Tim4
      for TAM-stimulated efferocytosis, whereas efferocytosis by thioglycollate
      elicited peritoneal macrophages or primary cultured microglia was TAM dependent,
      but not Tim4 dependent. These results indicate that TAM and Tim4 collaborate for
      efficient efferocytosis in certain macrophage populations.

PMID- 28768812
TI  - Reply to Hettinger: Hydrophobic unnatural base pairs and the expansion of the
      genetic alphabet.

PMID- 28768811
TI  - Conformational and chemical selection by a trans-acting editing domain.
AB  - Molecular sieves ensure proper pairing of tRNAs and amino acids during aminoacyl
      tRNA biosynthesis, thereby avoiding detrimental effects of mistranslation on cell
      growth and viability. Mischarging errors are often corrected through the activity
      of specialized editing domains present in some aminoacyl-tRNA synthetases or via
      single-domain trans-editing proteins. ProXp-ala is a ubiquitous trans-editing
      enzyme that edits Ala-tRNAPro, the product of Ala mischarging by prolyl-tRNA
      synthetase, although the structural basis for discrimination between correctly
      charged Pro-tRNAPro and mischarged Ala-tRNAAla is unclear. Deacylation assays
      using substrate analogs reveal that size discrimination is only one component of
      selectivity. We used NMR spectroscopy and sequence conservation to guide
      extensive site-directed mutagenesis of Caulobacter crescentus ProXp-ala, along
      with binding and deacylation assays to map specificity determinants. Chemical
      shift perturbations induced by an uncharged tRNAPro acceptor stem mimic,
      microhelixPro, or a nonhydrolyzable mischarged Ala-microhelixPro substrate analog
      identified residues important for binding and deacylation. Backbone 15N NMR
      relaxation experiments revealed dynamics for a helix flanking the substrate
      binding site in free ProXp-ala, likely reflecting sampling of open and closed
      conformations. Dynamics persist on binding to the uncharged microhelix, but are
      attenuated when the stably mischarged analog is bound. Computational docking and
      molecular dynamics simulations provide structural context for these findings and
      predict a role for the substrate primary alpha-amine group in substrate
      recognition. Overall, our results illuminate strategies used by a trans-editing
      domain to ensure acceptance of only mischarged Ala-tRNAPro, including
      conformational selection by a dynamic helix, size-based exclusion, and optimal
      positioning of substrate chemical groups.

PMID- 28768813
TI  - Helix instability and self-pairing prevent unnatural base pairs from expanding
      the genetic alphabet.

PMID- 28768814
TI  - Construction and Optimization of a Large Gene Coexpression Network in Maize Using
      RNA-Seq Data.
AB  - With the emergence of massively parallel sequencing, genomewide expression data
      production has reached an unprecedented level. This abundance of data has greatly
      facilitated maize research, but may not be amenable to traditional analysis
      techniques that were optimized for other data types. Using publicly available
      data, a gene coexpression network (GCN) can be constructed and used for gene
      function prediction, candidate gene selection, and improving understanding of
      regulatory pathways. Several GCN studies have been done in maize (Zea mays),
      mostly using microarray datasets. To build an optimal GCN from plant materials
      RNA-Seq data, parameters for expression data normalization and network inference
      were evaluated. A comprehensive evaluation of these two parameters and a ranked
      aggregation strategy on network performance, using libraries from 1266 maize
      samples, were conducted. Three normalization methods and 10 inference methods,
      including six correlation and four mutual information methods, were tested. The
      three normalization methods had very similar performance. For network inference,
      correlation methods performed better than mutual information methods at some
      genes. Increasing sample size also had a positive effect on GCN. Aggregating
      single networks together resulted in improved performance compared to single
      networks.

PMID- 28768815
TI  - Synthesis and Self-Assembly of Cellulose Microfibrils from Reconstituted
      Cellulose Synthase.
AB  - Cellulose, the major component of plant cell walls, can be converted to
      bioethanol and is thus highly studied. In plants, cellulose is produced by
      cellulose synthase, a processive family-2 glycosyltransferase. In plant cell
      walls, individual beta-1,4-glucan chains polymerized by CesA are assembled into
      microfibrils that are frequently bundled into macrofibrils. An in vitro system in
      which cellulose is synthesized and assembled into fibrils would facilitate
      detailed study of this process. Here, we report the heterologous expression and
      partial purification of His-tagged CesA5 from Physcomitrella patens Immunoblot
      analysis and mass spectrometry confirmed enrichment of PpCesA5. The recombinant
      protein was functional when reconstituted into liposomes made from yeast total
      lipid extract. The functional studies included incorporation of radiolabeled Glc,
      linkage analysis, and imaging of cellulose microfibril formation using
      transmission electron microscopy. Several microfibrils were observed either
      inside or on the outer surface of proteoliposomes, and strikingly, several
      thinner fibrils formed ordered bundles that either covered the surfaces of
      proteoliposomes or were spawned from liposome surfaces. We also report this
      arrangement of fibrils made by proteoliposomes bearing CesA8 from hybrid aspen.
      These observations describe minimal systems of membrane-reconstituted CesAs that
      polymerize beta-1,4-glucan chains that coalesce to form microfibrils and higher
      ordered macrofibrils. How these micro- and macrofibrils relate to those found in
      primary and secondary plant cell walls is uncertain, but their presence enables
      further study of the mechanisms that govern the formation and assembly of
      fibrillar cellulosic structures and cell wall composites during or after the
      polymerization process controlled by CesA proteins.

PMID- 28768817
TI  - CXCR4-Specific Nanobodies as Potential Therapeutics for WHIM syndrome.
AB  - WHIM syndrome is a rare congenital immunodeficiency disease, named after its main
      clinical manifestations: warts, hypogammaglobulinemia, infections, and
      myelokathexis, which refers to abnormal accumulation of mature neutrophils in the
      bone marrow. The disease is primarily caused by C-terminal truncation mutations
      of the chemokine receptor CXCR4, giving these CXCR4-WHIM mutants a gain of
      function in response to their ligand CXCL12. Considering the broad functions of
      CXCR4 in maintaining leukocyte homeostasis, patients are panleukopenic and
      display altered immune responses, likely as a consequence of impairment in the
      differentiation and trafficking of leukocytes. Treatment of WHIM patients
      currently consists of symptom relief, leading to unsatisfactory clinical
      responses. As an alternative and potentially more effective approach, we tested
      the potency and efficacy of CXCR4-specific nanobodies on inhibiting CXCR4-WHIM
      mutants. Nanobodies are therapeutic proteins based on the smallest functional
      fragments of heavy chain antibodies. They combine the advantages of small
      molecule drugs and antibody-based therapeutics due to their relative small size,
      high stability, and high affinity. We compared the potential of monovalent and
      bivalent CXCR4-specific nanobodies to inhibit CXCL12-induced CXCR4-WHIM-mediated
      signaling with the small-molecule clinical candidate AMD3100. The CXCR4-targeting
      nanobodies displace CXCL12 binding and bind CXCR4-wild type and CXCR4-WHIM
      (R334X/S338X) mutants and with (sub-) nanomolar affinities. The nanobodies'
      epitope was mapped to extracellular loop 2 of CXCR4, overlapping with the binding
      site of CXCL12. Monovalent, and in particular bivalent, nanobodies were more
      potent than AMD3100 in reducing CXCL12-mediated G protein activation. In
      addition, CXCR4-WHIM-dependent calcium flux and wound healing of human
      papillomavirus-immortalized cell lines in response to CXCL12 was effectively
      inhibited by the nanobodies. Based on these in vitro results, we conclude that
      CXCR4 nanobodies hold significant potential as alternative therapeutics for CXCR4
      associated diseases such as WHIM syndrome.

PMID- 28768816
TI  - Functional Specialization of Cellulose Synthase Isoforms in a Moss Shows
      Parallels with Seed Plants.
AB  - The secondary cell walls of tracheary elements and fibers are rich in cellulose
      microfibrils that are helically oriented and laterally aggregated. Support cells
      within the leaf midribs of mosses deposit cellulose-rich secondary cell walls,
      but their biosynthesis and microfibril organization have not been examined.
      Although the Cellulose Synthase (CESA) gene families of mosses and seed plants
      diversified independently, CESA knockout analysis in the moss Physcomitrella
      patens revealed parallels with Arabidopsis (Arabidopsis thaliana) in CESA
      functional specialization, with roles for both subfunctionalization and
      neofunctionalization. The similarities include regulatory uncoupling of the CESAs
      that synthesize primary and secondary cell walls, a requirement for two or more
      functionally distinct CESA isoforms for secondary cell wall synthesis,
      interchangeability of some primary and secondary CESAs, and some CESA redundancy.
      The cellulose-deficient midribs of ppcesa3/8 knockouts provided negative controls
      for the structural characterization of stereid secondary cell walls in wild type
      P. patens Sum frequency generation spectra collected from midribs were consistent
      with cellulose microfibril aggregation, and polarization microscopy revealed
      helical microfibril orientation only in wild type leaves. Thus, stereid secondary
      walls are structurally distinct from primary cell walls, and they share
      structural characteristics with the secondary walls of tracheary elements and
      fibers. We propose a mechanism for the convergent evolution of secondary walls in
      which the deposition of aggregated and helically oriented microfibrils is coupled
      to rapid and highly localized cellulose synthesis enabled by regulatory
      uncoupling from primary wall synthesis.

PMID- 28768818
TI  - Sofia intermediate catheter and the SNAKE technique: safety and efficacy of the
      Sofia catheter without guidewire or microcatheter construct.
AB  - BACKGROUND: Neurointerventional surgeries (NIS) benefit from supportive
      endovascular constructs. Sofia is a soft-tipped, flexible, braided single lumen
      intermediate catheter designed for NIS. Sofia advancement from the cervical to
      the intracranial circulation without a luminal guidewire or microcatheter
      construct has not been described. OBJECTIVE: To evaluate the efficacy and safety
      of the new Sofia Non-wire Advancement techniKE (SNAKE) for advancement of the
      Sofia into the cerebral circulation. METHODS: Consecutive patients who underwent
      NIS using Sofia were identified. Patient information, SNAKE use, and patient
      outcome were determined from electronic medical records. Sofia advancement to the
      cavernous internal carotid artery or the V2/V3 segment junction of the vertebral
      artery was the primary outcome measure. Secondary outcomes included arterial
      vasospasm and arterial dissection. RESULTS: 263 Patients (181 females, 69%) who
      underwent a total of 305 NIS using Sofia were identified. SNAKE (SNAKE+) was used
      in 187 procedures (61%). Two hundred and ninety-three procedures (96%) were
      technically successful, which included 184 SNAKE+ NIS and 109 SNAKE- NIS. Primary
      outcome was achieved in all SNAKE+ procedures, but not in five SNAKE- procedures
      (2%). No arterial dissections were identified among 305 interventions. In the
      intracranial circulation, a single SNAKE+ patient (0.5%) had non-flow limiting
      arterial vasospasm involving the petrous internal carotid. Three SNAKE+ patients
      (1.6%) and one SNAKE- patient (0.8%) demonstrated external carotid artery branch
      artery vasospasm during dural arteriovenous fistula or facial arteriovenous
      malformation treatment. CONCLUSION: SNAKE is a safe and effective technique for
      Sofia advancement. Sofia is a highly effective and safe intermediate catheter for
      a variety of NIS.

PMID- 28768819
TI  - Rabbit aneurysm models mimic histologic wall types identified in human
      intracranial aneurysms.
AB  - BACKGROUND: Semiquantitative scales correlate histopathologic findings in the
      walls of human aneurysms with rupture status. OBJECTIVE: To apply a
      semiquantitative scale to the rabbit elastase-induced aneurysm model to determine
      whether rabbit histologic types mimic the full range of histologic subtypes of
      humans. MATERIALS AND METHODS: Twenty-seven elastase-induced female rabbit
      aneurysms were studied, harvested at 2 weeks (n=5) and 12 weeks (n=22). Paraffin
      embedded sections received hematoxylin-eosin and Verhoeff-Van Gieson staining.
      Immunohistochemistry was performed for alpha-smooth muscle actin and CD31 for
      endothelial cells. A semiquantitative scale was used for scoring based on human
      aneurysm tissue, divided into four subtypes according to cellular and
      extracellular matrix findings: type A, linear organized smooth muscle cells
      (SMCs) and intact endothelium; type B, thickened wall with disorganized,
      proliferating SMCs; type C, thick, collagenized and hypocellular wall with or
      without organizing thrombosis, and type D, extremely thin, hypocellular wall.
      Separate scoring was performed of the aneurysm neck and proximal and distal
      zones. RESULTS: Findings compatible with all subtypes of human aneurysm tissue
      were identified. Types A and C were found in 13 (48%) and 11 (41%) of 27
      aneurysms and in the proximal and distal wall at both time points. Type B was
      found in 16 aneurysms (59%), exclusively at the neck at both time points; type D,
      in 14 aneurysms (52%), exclusively at proximal and distal zones of 12-week
      aneurysms. CONCLUSIONS: The wall of elastase-induced rabbit aneurysm demonstrates
      histologic findings similar to the four categories of human cerebral aneurysms
      based on cellular and extracellular wall content.

PMID- 28768820
TI  - Thrombectomy versus medical management for large vessel occlusion strokes with
      minimal symptoms: an analysis from STOPStroke and GESTOR cohorts.
AB  - INTRODUCTION: It remains unclear whether patients presenting with large vessel
      occlusion strokes and mild symptoms benefit from thrombectomy. OBJECTIVE: To
      compare outcomes of endovascular therapy versus medical management in patients
      with large vessel occlusion strokes and National Institute of Health Stroke Scale
      (NIHSS) score <=5. METHODS: This was a retrospective analysis combining two large
      prospectively collected datasets including patients with (1) admission NIHSS
      score <=5, (2) premorbid modified Rankin Scale (mRS) score 0-2, and (3) middle
      cerebral-M1/M2, intracranial carotid, anterior cerebral or basilar artery
      occlusions. Groups receiving (1) endovascular treatment and (2) medical
      management were compared. The primary and secondary outcome measures were NIHSS
      shift (discharge NIHSS minus admission NIHSS) and the rates of mRS 0-2 at
      discharge and 3-6 months, respectively. Univariate, multivariate, and matched
      analyses were performed. RESULTS: Eighty-eight patients received medical
      management and 30 thrombectomy. Multivariable analysis indicated thrombectomy was
      the only predictor of favorable NIHSS shift (beta -3.7, 95% CI -6.0 to -1.5,
      p=0.02), as well as independence at discharge (beta -21.995% CI -41.4to -20.8,
      p<0.01) and 3-6-month follow-up (beta -21.1, 95% CI -39.1 to -19.7, p<0.01). A
      matched analysis (based on age, baseline NIHSS and intravenous tissue plasminogen
      activator use) produced 26 pairs. Endovascular therapy was statistically
      associated with lower NIHSS at discharge (p=0.04), favorable NIHSS shift
      (p=0.03), and increased independence rates at discharge (p=0.03) and 3-6-month
      follow-up (p=0.04). CONCLUSION: In patients presenting with minimal stroke
      symptoms (NIHSS score <=5) and large vessel occlusion strokes, mechanical
      thrombectomy appears to be associated with a favorable shift of NIHSS at
      discharge, as well as higher rates of independence at discharge and long-term
      follow-up. Confirmatory prospective studies are warranted.

PMID- 28768821
TI  - Complementary and alternative treatments of multiple sclerosis: a review of the
      evidence from 2001 to 2016.
AB  - People with multiple sclerosis (PwMS) commonly use complementary and alternative
      medicines (CAM), but an understanding of their efficacy is lacking. Here, we
      quantitatively review the class I and class II studies of treatment efficacy for
      multiple sclerosis from January 2001 to January 2017, in order to assess the
      modern evidence for CAM use. The 38 studies included in this review are divided
      across five CAM types (cannabis, diet, exercise, psychological approaches and
      other). We found little evidence to support CAM efficacy. The studies contained
      little replication in intervention, primary outcomes or study design. Six of 16
      CAMs included in this review were only researched in a single study. Future work
      in this area should build consensus around study methodologies and primary
      outcomes.

PMID- 28768822
TI  - Intravenous immunoglobulin for maintenance treatment of chronic inflammatory
      demyelinating polyneuropathy: a multicentre, open-label, 52-week phase III trial.
AB  - OBJECTIVE: Short-term efficacy of induction therapy with intravenous
      immunoglobulin (Ig) in patients with chronic inflammatory demyelinating
      polyneuropathy (CIDP) is well established. However, data of previous studies on
      maintenance therapy were limited up to 24-week treatment period. We aimed to
      investigate the efficacy and safety of longer-term intravenous Ig therapy for 52
      weeks. METHODS: This study was an open-label phase 3 clinical trial conducted in
      49 Japanese tertiary centres. 49 patients with CIDP who fulfilled diagnostic
      criteria were included. After an induction intravenous Ig therapy (0.4 g/kg/day
      for five consecutive days), maintenance dose intravenous Ig (1.0 g/kg) was given
      every 3 weeks for up to 52 weeks. The primary outcome measures were the responder
      rate at week 28 and relapse rate at week 52. The response and relapse were
      defined with the adjusted Inflammatory Neuropathy Cause and Treatment scale.
      RESULTS: At week 28, the responder rate was 77.6% (38/49 patients; 95% CI 63% to
      88%), and the 38 responders continued the maintenance therapy. At week 52, 4 of
      the 38 (10.5%) had a relapse (95% CI 3% to 25%). During 52 weeks, 34 (69.4%) of
      the 49 enrolled patients had a maintained improvement. Adverse events were
      reported in 94% of the patients; two patients (66-year-old and 76-year-old men
      with hypertension or diabetes) developed cerebral infarction (lacunar infarct
      with good recovery), and the other adverse effects were mild and resolved by the
      end of the study period. CONCLUSIONS: Maintenance treatment with 1.0 g/kg
      intravenous Ig every 3 weeks is an efficacious therapy for patients with CIDP,
      and approximately 70% of them had a sustained remission for 52 weeks. Thrombotic
      complications should be carefully monitored, particularly in elderly patients
      with vascular risk factors. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
      (NCT01824251).

PMID- 28768823
TI  - Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin.
AB  - Elevated, nontoxic doses of manganese (Mn) protect against Shiga toxin-1-induced
      cell death via down-regulation of GPP130, a cycling Golgi membrane protein that
      serves as an endosome-to-Golgi trafficking receptor for the toxin. Mn binds to
      GPP130 in the Golgi and causes GPP130 to oligomerize/aggregate, and the complexes
      are diverted to lysosomes. In fact, based on experiments using the self
      interacting FM domain, it appears generally true that aggregation of a Golgi
      protein leads to its lysosomal degradation. How such oligomers are selectively
      sorted out of the Golgi is unknown. Here we provide evidence that Mn-induced exit
      of GPP130 from the trans-Golgi network (TGN) toward lysosomes is mediated by the
      sorting receptor sortilin interacting with the lumenal stem domain of GPP130. In
      contrast, FM-induced lysosomal trafficking of the Golgi protein
      galactosyltransferase was sortilin independent and occurred even in the absence
      of its native lumenal domain. Thus sortilin-dependent as well as sortilin
      independent sorting mechanisms target aggregated Golgi membrane proteins for
      lysosomal degradation.

PMID- 28768824
TI  - ALADIN is required for the production of fertile mouse oocytes.
AB  - Asymmetric cell divisions depend on the precise placement of the spindle
      apparatus. In mammalian oocytes, spindles assemble close to the cell's center,
      but chromosome segregation takes place at the cell periphery where half of the
      chromosomes are expelled into small, nondeveloping polar bodies at anaphase. By
      dividing so asymmetrically, most of the cytoplasmic content within the oocyte is
      preserved, which is critical for successful fertilization and early development.
      Recently we determined that the nucleoporin ALADIN participates in spindle
      assembly in somatic cells, and we have also shown that female mice homozygously
      null for ALADIN are sterile. In this study we show that this protein is involved
      in specific meiotic stages, including meiotic resumption, spindle assembly, and
      spindle positioning. In the absence of ALADIN, polar body extrusion is
      compromised due to problems in spindle orientation and anchoring at the first
      meiotic anaphase. ALADIN null oocytes that mature far enough to be fertilized in
      vitro are unable to support embryonic development beyond the two-cell stage.
      Overall, we find that ALADIN is critical for oocyte maturation and appears to be
      far more essential for this process than for somatic cell divisions.

PMID- 28768825
TI  - Basolateral delivery of the type I transforming growth factor beta receptor is
      mediated by a dominant-acting cytoplasmic motif.
AB  - Delivery of biomolecules to the correct subcellular locales is critical for
      proper physiological function. To that end, we have previously determined that
      type I and II transforming growth factor beta (TGF-beta) receptors (TbetaRI and
      TbetaRII, respectively) localize to the basolateral domain in polarized
      epithelia. While TbetaRII targeting was shown to be regulated by sequences
      between amino acids 529 and 538, the analogous region(s) within TbetaRI is
      unknown. To address that question, sequential cytoplasmic TbetaRI truncations and
      point mutations identified a targeting motif between residues 158 and 163
      (VxxEED) required for basolateral TbetaRI expression. Further studies documented
      that receptor internalization, down-regulation, direct recycling, or Smad
      signaling were unaffected by motif mutations that caused TbetaRI mislocalization.
      However, inclusion of amino acids 148-217 containing the targeting motif was able
      to direct basolateral expression of the apically sorted nerve growth factor
      receptor (NGFR, p75; extracellular and transmembrane regions) in a dominant
      manner. Finally, coexpression of apically targeted type I and type II TGF-beta
      receptors mediated Smad3 signaling from the apical membrane of polarized
      epithelial cells. These findings demonstrate that the absence of apical TGF-beta
      signaling in normal epithelia is primarily a reflection of domain-specific
      receptor expression and not an inability to couple with the signaling machinery.

PMID- 28768826
TI  - Mechanical signals activate p38 MAPK pathway-dependent reinforcement of actin via
      mechanosensitive HspB1.
AB  - Despite the importance of a cell's ability to sense and respond to mechanical
      force, the molecular mechanisms by which physical cues are converted to cell
      instructive chemical information to influence cell behaviors remain to be
      elucidated. Exposure of cultured fibroblasts to uniaxial cyclic stretch results
      in an actin stress fiber reinforcement response that stabilizes the actin
      cytoskeleton. p38 MAPK signaling is activated in response to stretch, and
      inhibition of p38 MAPK abrogates stretch-induced cytoskeletal reorganization.
      Here we show that the small heat shock protein HspB1 (hsp25/27) is phosphorylated
      in stretch-stimulated mouse fibroblasts via a p38 MAPK-dependent mechanism.
      Phosphorylated HspB1 is recruited to the actin cytoskeleton, displaying prominent
      accumulation on actin "comet tails" that emanate from focal adhesions in stretch
      stimulated cells. Site-directed mutagenesis to block HspB1 phosphorylation
      inhibits the protein's cytoskeletal recruitment in response to mechanical
      stimulation. HspB1-null cells, generated by CRISPR/Cas9 nuclease genome editing,
      display an abrogated stretch-stimulated actin reinforcement response and
      increased cell migration. HspB1 is recruited to sites of increased traction force
      in cells geometrically constrained on micropatterned substrates. Our findings
      elucidate a molecular pathway by which a mechanical signal is transduced via
      activation of p38 MAPK to influence actin remodeling and cell migration via a
      zyxin-independent process.

PMID- 28768827
TI  - Ubiquitin orchestrates proteasome dynamics between proliferation and quiescence
      in yeast.
AB  - Proteasomes are essential for protein degradation in proliferating cells. Little
      is known about proteasome functions in quiescent cells. In nondividing yeast, a
      eukaryotic model of quiescence, proteasomes are depleted from the nucleus and
      accumulate in motile cytosolic granules termed proteasome storage granules
      (PSGs). PSGs enhance resistance to genotoxic stress and confer fitness during
      aging. Upon exit from quiescence PSGs dissolve, and proteasomes are rapidly
      delivered into the nucleus. To identify key players in PSG organization, we
      performed high-throughput imaging of green fluorescent protein (GFP)-labeled
      proteasomes in the yeast null-mutant collection. Mutants with reduced levels of
      ubiquitin are impaired in PSG formation. Colocalization studies of PSGs with
      proteins of the yeast GFP collection, mass spectrometry, and direct stochastic
      optical reconstitution microscopy of cross-linked PSGs revealed that PSGs are
      densely packed with proteasomes and contain ubiquitin but no polyubiquitin
      chains. Our results provide insight into proteasome dynamics between
      proliferating and quiescent yeast in response to cellular requirements for
      ubiquitin-dependent degradation.

PMID- 28768828
TI  - Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast
      cells.
AB  - One proposed mechanism of cellular aging is the gradual loss of certain cellular
      components that are insufficiently renewed. In an earlier study, multidrug
      resistance transporters (MDRs) were postulated to be such aging determinants
      during the yeast replicative life span (RLS). Aged MDR proteins were
      asymmetrically retained by the aging mother cell and did not diffuse freely into
      the bud, whereas newly synthesized MDR proteins were thought to be deposited
      mostly in the bud before cytokinesis. In this study, we further demonstrate the
      proposed age asymmetry of MDR proteins in dividing yeast cells and investigate
      the mechanism that controls diffusive properties of MDR proteins to maintain this
      asymmetry. We found that long-chain sphingolipids, but not the septin/endoplasmic
      reticulum-based membrane diffusion barrier, are important for restricting MDR
      diffusion. Depletion of sphingolipids or shortening of their long acyl chains
      resulted in an increase in the lateral mobility of MDR proteins, causing aged MDR
      protein in the mother cell to enter the bud. We used a mathematical model to
      understand the effect of diminished MDR age asymmetry on yeast cell aging, the
      result of which was qualitatively consistent with the observed RLS shortening in
      sphingolipid mutants.

PMID- 28768829
TI  - The SAGA complex, together with transcription factors and the endocytic protein
      Rvs167p, coordinates the reprofiling of gene expression in response to changes in
      sterol composition in Saccharomyces cerevisiae.
AB  - Changes in cellular sterol species and concentrations can have profound effects
      on the transcriptional profile. In yeast, mutants defective in sterol
      biosynthesis show a wide range of changes in transcription, including a
      coinduction of anaerobic genes and ergosterol biosynthesis genes, biosynthesis of
      basic amino acids, and several stress genes. However the mechanisms underlying
      these changes are unknown. We identified mutations in the SAGA complex, a
      coactivator of transcription, which abrogate the ability to carry out most of
      these sterol-dependent transcriptional changes. In the erg3 mutant, the SAGA
      complex increases its occupancy time on many of the induced ergosterol and
      anaerobic gene promoters, increases its association with several relevant
      transcription factors and the SWI/SNF chromatin remodeling complex, and
      surprisingly, associates with an endocytic protein, Rvs167p, suggesting a
      moonlighting function for this protein in the sterol-regulated induction of the
      heat shock protein, HSP42 and HSP102, mRNAs.

PMID- 28768830
TI  - Neurodegeneration-associated mutant TREM2 proteins abortively cycle between the
      ER and ER-Golgi intermediate compartment.
AB  - Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane
      protein expressed on microglia within the brain. Several rare mutations in TREM2
      cause an early-onset form of neurodegeneration when inherited homozygously. Here
      we investigate how these mutations affect the intracellular transport of TREM2.
      We find that most pathogenic TREM2 mutant proteins fail to undergo normal
      maturation in the Golgi complex and show markedly reduced cell-surface
      expression. Prior research has suggested that two such mutants are retained in
      the endoplasmic reticulum (ER), but we find, using a cell-free coat protein
      complex II (COPII) vesicle budding reaction, that mutant TREM2 is exported
      efficiently from the ER. In addition, mutant TREM2 becomes sensitive to cleavage
      by endoglycosidase D under conditions that inhibit recycling to the ER,
      indicating that it normally reaches a post-ER compartment. Maturation-defective
      TREM2 mutants are also efficiently bound by a lectin that recognizes O-glycans
      added in the ER-Golgi intermediate compartment (ERGIC) and cis-Golgi cisterna.
      Finally, mutant TREM2 accumulates in the ERGIC in cells depleted of COPI. These
      results indicate that efficient ER export is not sufficient to enable normal cell
      surface expression of TREM2. Moreover, our findings suggest that the ERGIC may
      play an underappreciated role as a quality-control center for mutant and/or
      malformed membrane proteins.

PMID- 28768831
TI  - Two International Round-Robin Studies Showed Good Comparability of 5
      Methyltetrahydrofolate but Poor Comparability of Folic Acid Measured in Serum by
      Different High-Performance Liquid Chromatography-Tandem Mass Spectrometry
      Methods.
AB  - Background: Serum folate methods produce different results. The comparability of
      HPLC-mass spectrometry (MS)/MS methods is not well documented.Objective: We
      conducted an international "round-robin" investigation to assess the
      comparability, precision, and accuracy of serum folate HPLC-MS/MS
      methods.Methods: The CDC laboratory, 7 laboratories with independently developed
      methods (group 1), and 6 laboratories with an adapted CDC method (group 2)
      analyzed folate forms in 6 serum pools and 6 calibrators from the CDC (duplicate
      analysis over 2 d) and in two 3-level reference materials (duplicate
      analysis).Results: All laboratories measured 5-methyltetrahydrofolate (5
      methylTHF) and folic acid; some measured additional folate forms. The geometric
      mean (range) concentrations (nanomoles per liter) for 5-methylTHF in the 6 serum
      pools were 18.3 nmol/L (CDC), 13.8-28.9 nmol/L (group 1), and 16.8-18.6 nmol/L
      (group 2); for folic acid the concentrations were 3.42 nmol/L (CDC), 1.09-4.74
      nmol/L (group 1), and 1.74-2.90 nmol/L (group 2). The median imprecision (CV) for
      5-methylTHF was 4.1% (CDC), 4.6-11% (group 1), and 1.7-6.0% (group 2); for folic
      acid it was 6.9% (CDC), 4.9-20% (group 1), and 3.9-23% (group 2). The mean +/- SD
      (range) recovery of 5-methylTHF spiked into serum was 98% +/- 27% (59-138%) for
      group 1 and 98% +/- 10% (82-111%) for group 2; for folic acid it was 93% +/- 29%
      (67-198%) for group 1 and 81% +/- 16% (64-102%) for group 2. The mean relative
      bias for 5-methylTHF compared with the reference material certificate value was
      12% (CDC), -24% to 30% (group 1), and -0.6% to 16% (group 2); for folic acid it
      was 73% (CDC), -47% to 578% (group 1), and -3.3% to 67% (group 2).Conclusions:
      For 5-methylTHF, group 2 laboratories demonstrated better agreement and
      precision, less variable spiking recovery, and less bias by using a reference
      material. Laboratory performance for folic acid was highly variable and needs
      improvement. Certified reference materials for serum folate forms and total
      folate are needed to improve method accuracy.

PMID- 28768833
TI  - Leucine-Induced Upregulation of Terminal Oligopyrimidine mRNA Translation in
      Skeletal Muscle: Just the Tip of the Iceberg?

PMID- 28768832
TI  - Dietary Fat Quantity and Type Induce Transcriptome-Wide Effects on Alternative
      Splicing of Pre-mRNA in Rat Skeletal Muscle.
AB  - Background: Fat-enriched diets produce metabolic changes in skeletal muscle,
      which in turn can mediate changes in gene regulation.Objective: We examined the
      high-fat-diet-induced changes in skeletal muscle gene expression by
      characterizing variations in pre-mRNA alternative splicing.Methods: Affymetrix
      Exon Array analysis was performed on the transcriptome of the
      gastrocnemius/plantaris complex of male obesity-prone Sprague-Dawley rats fed a
      10% or 60% fat (lard) diet for 2 or 8 wk. The validation of exon array results
      was focused on troponin T (Tnnt3). Tnnt3 splice form analyses were extended in
      studies of rats fed 10% or 30% fat diets across 1- to 8-wk treatment periods and
      rats fed 10% or 45% fat diets with fat sources from lard or mono- or
      polyunsaturated fats for 2 wk. Nuclear magnetic resonance (NMR) was used to
      measure body composition.Results: Consumption of a 60% fat diet for 2 or 8 wk
      resulted in alternative splicing of 668 and 726 pre-mRNAs, respectively, compared
      with rats fed a 10% fat diet. Tnnt3 transcripts were alternatively spliced in
      rats fed a 60% fat diet for either 2 or 8 wk. The high-fat-diet-induced changes
      in Tnnt3 alternative splicing were observed in rats fed a 30% fat diet across 1-
      to 8-wk treatment periods. Moreover, this effect depended on fat type, because
      Tnnt3 alternative splicing occurred in response to 45% fat diets enriched with
      lard but not in response to diets enriched with mono- or polyunsaturated fatty
      acids. Fat mass (a proxy for obesity as measured by NMR) did not differ between
      groups in any study.Conclusions: Rat skeletal muscle responds to overconsumption
      of dietary fat by modifying gene expression through pre-mRNA alternative
      splicing. Variations in Tnnt3 alternative splicing occur independently of obesity
      and are dependent on dietary fat quantity and suggest a role for saturated fatty
      acids in the high-fat-diet-induced modifications in Tnnt3 alternative splicing.

PMID- 28768834
TI  - Placentome Nutrient Transporters and Mammalian Target of Rapamycin Signaling
      Proteins Are Altered by the Methionine Supply during Late Gestation in Dairy Cows
      and Are Associated with Newborn Birth Weight.
AB  - Background: To our knowledge, most research demonstrating a link between maternal
      nutrition and both fetal growth and offspring development after birth has been
      performed with nonruminants. Whether such relationships exist in large ruminants
      is largely unknown.Objective: We aimed to investigate whether increasing the
      methionine supply during late pregnancy would alter uteroplacental tissue
      nutrient transporters and mammalian target of rapamycin (mTOR) and their relation
      with newborn body weight.Methods: Multiparous Holstein cows were used in a
      randomized complete block design experiment. During the last 28 d of pregnancy,
      cows were fed a control diet or the control diet plus ethylcellulose rumen
      protected methionine (0.9 g/kg dry matter intake) (Mepron; Evonik Nutrition &
      Care GmbH) to achieve a 2.8:1 ratio of lysine to methionine in the metabolizable
      protein reaching the small intestine. We collected placentome samples at
      parturition and used them to assess mRNA and protein expression and the
      phosphorylation status of mTOR pathway proteins.Results: Newborn body weight was
      greater in the methionine group than in the control group (44.1 kg and 41.8 kg,
      respectively; P <= 0.05). Increasing the methionine supply also resulted in
      greater feed intake (15.8 kg/d and 14.6 kg/d), plasma methionine (11.9 MUM and
      15.3 MUM), and plasma insulin (1.16 MUg/L and 0.81 MUg/L) in cows during late
      pregnancy. As a result, mRNA expression of genes involved in neutral amino acid
      transport [solute carrier (SLC) family members SLC3A2, SLC7A5, SLC38A1, and
      SLC38A10], glucose transport [SLC2A1, SLC2A3, and SLC2A4], and the mTOR pathway
      [mechanistic target of rapamycin and ribosomal protein S6 kinase B1] were
      upregulated (P <= 0.07) in methionine-supplemented cows. Among 6 proteins in the
      mTOR pathway, increasing the methionine supply led to greater (P <= 0.09) protein
      expression of alpha serine-threonine kinase (AKT), phosphorylated (p)-AKT, p
      eukaryotic elongation factor 2, and the p-mTOR:mTOR ratio.Conclusion:
      Supplemental methionine during late gestation increases feed intake and newborn
      body weight in dairy cows, and this effect may be mediated by alterations in the
      uteroplacental transport of nondispensable and dispensable amino acids and
      glucose at least in part through changes in gene transcription and mTOR
      signaling.

PMID- 28768835
TI  - Associations of Dairy Intake with Incident Prediabetes or Diabetes in Middle-Aged
      Adults Vary by Both Dairy Type and Glycemic Status.
AB  - Background: Inconsistent evidence describes the association between dietary
      intake of dairy and milk-based products and type 2 diabetes (T2D) risk.Objective:
      Our objective was to assess associations between consumption of milk-based
      products, incident prediabetes, and progression to T2D in the Framingham Heart
      Study Offspring Cohort.Methods: Total dairy and milk-based product consumption
      was assessed by <=4 food-frequency questionnaires across a mean of 12 y of follow
      up in 2809 participants [mean +/- SD age: 54.0 +/- 9.7 y; body mass index (in
      kg/m2): 27.1 +/- 4.7; 54% female]. Prediabetes was defined as the first
      occurrence of fasting plasma glucose >=5.6 to <7.0 mmol/L (>=100 to <126 mg/dL),
      and T2D was defined as the first occurrence of fasting plasma glucose >=7.0
      mmol/L (>=126 mg/dL) or diabetes treatment. Proportional hazards models were used
      to estimate the risk of incident outcomes relative to dairy product intake in
      subsets of the cohort who were at risk of developing the outcomes. Spline
      regressions were used to examine potential nonlinear relations.Results: Of 1867
      participants free of prediabetes at baseline, 902 (48%) developed prediabetes.
      Total, low-fat, and high-fat dairy consumptions were associated with a 39%, 32%,
      and 25% lower risk of incident prediabetes, respectively, in the highest compared
      with the lowest intakes (>=14 compared with <4 servings/wk). Total, low-fat and
      skim milk, whole-milk, and yogurt intakes were associated nonlinearly with
      incident prediabetes; moderate intake was associated with the greatest relative
      risk reduction. Neither cheese nor cream and butter was associated with
      prediabetes. Of 925 participants with prediabetes at baseline, 196 (21%)
      developed T2D. Only high-fat dairy and cheese showed evidence of dose-response,
      inverse associations with incident T2D, with 70% and 63% lower risk,
      respectively, of incident T2D between the highest and lowest intake categories
      (>=14 compared with <1 serving/wk for high-fat dairy, >=4 compared with <1
      serving/wk for cheese).Conclusion: Associations of dairy with incident
      prediabetes or diabetes varied both by dairy product and type and by baseline
      glycemic status in this middle-aged US population. Baseline glycemic status may
      partially underlie prior equivocal evidence regarding the role of dairy intake in
      diabetes.

PMID- 28768836
TI  - S-Equol Activates cAMP Signaling at the Plasma Membrane of INS-1 Pancreatic beta
      Cells and Protects against Streptozotocin-Induced Hyperglycemia by Increasing
      beta-Cell Function in Male Mice.
AB  - Background:S-equol, which is enantioselectively produced from daidzein by gut
      microbiota, has been suggested as a chemopreventive agent against type 2 diabetes
      mellitus (T2DM), but the underlying mechanisms remain unclear.Objective: We
      investigated the effects of S-equol on pancreatic beta-cell function.Methods:
      beta-Cell growth and insulin secretion were evaluated with male Institute of
      Cancer Research mice and isolated pancreatic islets from the mice, respectively.
      The mechanisms by which S-equol stimulated beta-cell response were examined in
      INS-1 beta-cells. The effect of S-equol treatment on beta-cell function was
      assessed in low-dose streptozotocin-treated mice. S-equol was used at 10 MUmol/L
      for in vitro and ex vivo studies and was administered by oral gavage (20 mg/kg, 2
      times/d throughout the experimental period) for in vivo studies.Results:S-equol
      administration for 7 d increased Ki67-positive beta-cells by 27% (P < 0.01) in
      mice. S-equol enantioselectively enhanced glucose-stimulated insulin secretion in
      mouse pancreatic islets by 41% (P < 0.001). In INS-1 cells, S-equol exerted
      stronger effects than daidzein on cell growth, insulin secretion, and cAMP
      response element (CRE)-mediated transcription. These S-equol effects were
      diminished by inhibiting protein kinase A. The effective concentration of S-equol
      for stimulating cAMP production at the plasma membrane was lower than that for
      phosphodiesterase inhibition. S-equol-stimulated CRE activation was negatively
      controlled by the knockdown of G-protein alpha subunit group S (stimulatory) and
      positively controlled by that of G-protein-coupled receptor kinase-3 and -6.
      Compared with vehicle-treated controls, S-equol gavage treatment resulted in an
      increase in beta-cell mass of 104% (P < 0.05), a trend toward high plasma insulin
      concentrations (by 118%; P = 0.06), and resistance to hyperglycemia after
      streptozotocin treatment (78% of AUC after glucose challenge; P < 0.01). S-equol
      administration significantly increased the number of Ki67-positive proliferating
      beta-cells by 62% (P < 0.01) and decreased that of terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling-positive apoptotic beta-cells by 75%
      (P < 0.05).Conclusions: Our results show that S-equol boosts beta-cell function
      and prevents hypoglycemia in mice, suggesting its potential for T2DM prevention.

PMID- 28768837
TI  - Vitamin D in the Spectrum of Prediabetes and Cardiovascular Autonomic
      Dysfunction.
AB  - Vitamin D is a fat-soluble secosteroid hormone with pleiotropic effects. 1,25
      Dihydroxyvitamin D coordinates the biosynthesis of neurotransmitters in the
      central nervous system, which regulate cardiovascular autonomic function and may
      explain its putative role in the development of cardiovascular autonomic
      neuropathy (CAN). CAN is an independent risk factor for mortality in patients
      with diabetes and prediabetes and is associated with an increased risk of
      developing type 2 diabetes and cardiovascular disease. Accumulating data indicate
      the presence of peripheral nerve injury at these early stages of dysglycemia and
      its multifactorial pathogenesis. Prediabetes is associated with vitamin D
      insufficiency. Vitamin D is proposed to prevent the progression of glucose
      intolerance. The putative underlying mechanisms include maintenance of the
      intracellular calcium concentration, direct stimulation of insulin receptor
      expression, and enhancement of the insulin response to glucose transporters.
      Vitamin D exerts a protective effect on peripheral nerve fibers by decreasing the
      demyelination process and inducing axonal regeneration. The effects of vitamin D
      supplementation on glucose tolerance and related autonomic nerve dysfunction have
      been a recent focus of scientific interest. Although well-designed observational
      studies are available, the causative relation between vitamin D deficiency,
      glucose intolerance, and CAN is still debatable. One reason might be that
      interventional studies are unpersuasive with regard to the beneficial clinical
      effects of vitamin D supplementation. Because of its favorable side effect
      profile, vitamin D supplementation might represent an attractive therapeutic
      option for treating the pandemic prevalence of prediabetes and vitamin D
      deficiency. Vitamin D supplementation can improve glucose tolerance and
      cardiovascular autonomic function and can thus reduce cardiovascular mortality
      among subjects with different stages of glucose intolerance and autonomic
      dysfunction. However, more patient-centered trials on the use of vitamin D
      supplementation in different conditions are needed.

PMID- 28768838
TI  - Perinatal Brain Docosahexaenoic Acid Concentration Has a Lasting Impact on
      Cognition in Mice.
AB  - Background: Premature infants are deprived of prenatal accumulation of brain
      docosahexaenoic acid [DHA (22:6n-3)], an omega-3 fatty acid [omega-3 FA (n-3 FA)]
      important for proper development of cognitive function. The resulting brain DHA
      deficit can be reversed by omega-3 FA supplementation.Objective: The objective
      was to test whether there is a critical period for providing omega-3 FA to
      correct cognitive deficits caused by developmental omega-3 FA deprivation in
      mice.Methods: Twelve timed-pregnant mice [embryonic day 14 (E14), C57/BL6NCr]
      were fed an omega-3 FA-deficient diet containing 0.04% alpha-linolenic acid [ALA
      (18:3n-3)], and their offspring were fed the same deficient diet (Def group) or
      changed to an omega-3 FA-adequate diet containing 3.1% ALA at 3 wk, 2 mo, or 4 mo
      of age. In parallel, 3 E14 pregnant mice were fed the adequate diet and their
      offspring were fed the same diet (Adeq group) throughout the experiment. Brain FA
      composition, learning and memory, and hippocampal synaptic protein expression
      were evaluated at 6 mo by gas chromatography, the Morris water maze test, and
      western blot analysis, respectively.Results: Maternal dietary omega-3 FA
      deprivation decreased DHA by >50% in the brain of their offspring at 3 wk of age.
      The Def group showed significantly worse learning and memory at 6 mo than those
      groups fed the adequate diet. These pups also had decreased hippocampal
      expression of postsynaptic density protein 95 (43% of Adeq group), Homer protein
      homolog 1 (21% of Adeq group), and synaptosome-associated protein of 25 kDa (64%
      of Adeq group). Changing mice to the adequate diet at 3 wk, 2 mo, or 4 mo of age
      restored brain DHA to the age-matched adequate concentration. However, deficits
      in hippocampal synaptic protein expression and spatial learning and memory were
      normalized only when the diet was changed at 3 wk.Conclusion: Developmental
      deprivation of brain DHA by dietary omega-3 FA depletion in mice may have a
      lasting impact on cognitive function if not corrected at an early age.

PMID- 28768839
TI  - Serum Soluble Transferrin Receptor Concentrations Are Elevated in Congolese
      Children with Glucose-6-Phosphate Dehydrogenase Variants, but Not Sickle Cell
      Variants or alpha-Thalassemia.
AB  - Background: Anemia is common in Congolese children, and inherited blood disorders
      may be a contributing cause. The presence of sickle cell variants, X-linked
      glucose-6-phosphate dehydrogenase (G6PD) deficiency and alpha-thalassemia, has
      been previously reported. G6PD A- deficiency is characterized by the co
      inheritance of G6PD 376 and 202 variants and is common in sub-Saharan
      Africa.Objective: We aimed to measure the associations between inherited blood
      disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR)
      concentrations in Congolese children.Methods: Venous blood was collected from 744
      children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and
      inflammation status and malaria. Pyrosequencing was used to detect sickle cell
      variants. Polymerase chain reaction was used to detect G6PD variants and alpha
      thalassemia deletions.Results: Overall, 11% of children had a sickle cell
      variant, 19% of boys were G6PD A- hemizygotes, 12% and 10% of girls were G6PD A-
      hetero- or homozygotes, respectively, and 12% of children had alpha-thalassemia.
      Multivariable linear regression models (adjusted for age, province, altitude,
      malaria, and biomarkers of nutritional and inflammation status) showed that G6PD
      A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations
      [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53),
      respectively] than children with no G6PD variants. Hemoglobin and ferritin
      concentrations were not independently associated with any of the inherited blood
      disorder genotypes.Conclusions: We found that 2 G6PD variant genotypes were
      associated with elevated sTfR concentrations, which limits the accuracy of sTfR
      as a biomarker of iron status in this population.

PMID- 28768840
TI  - Thalamic deep brain stimulation for tremor in Parkinson disease, essential
      tremor, and dystonia.
AB  - OBJECTIVE: To report on the long-term outcomes of deep brain stimulation (DBS) of
      the thalamic ventral intermediate nucleus (VIM) in Parkinson disease (PD),
      essential tremor (ET), and dystonic tremor. METHODS: One hundred fifty-nine
      patients with PD, ET, and dystonia underwent VIM DBS due to refractory tremor at
      the Grenoble University Hospital. The primary outcome was a change in the tremor
      scores at 1 year after surgery and at the latest follow-up (21 years). Secondary
      outcomes included the relationship between tremor score reduction over time and
      the active contact position. Tremor scores (Unified Parkinson's Disease Rating
      Scale-III, items 20 and 21; Fahn, Tolosa, Marin Tremor Rating Scale) and the
      coordinates of the active contacts were recorded. RESULTS: Ninety-eight patients
      were included. Patients with PD and ET had sustained improvement in tremor with
      VIM stimulation (mean improvement, 70% and 66% at 1 year; 63% and 48% beyond 10
      years, respectively; p < 0.05). There was no significant loss of stimulation
      benefit over time (p > 0.05). Patients with dystonia exhibited a moderate
      response at 1-year follow-up (41% tremor improvement, p = 0.027), which was not
      sustained after 5 years (30% improvement, p = 0.109). The more dorsal active
      contacts' coordinates in the right lead were related to a better outcome 1 year
      after surgery (p = 0.029). During the whole follow-up, forty-eight patients (49%)
      experienced minor side effects, whereas 2 (2.0%) had serious events (brain
      hemorrhage and infection). CONCLUSIONS: VIM DBS is an effective long-term (beyond
      10 years) treatment for tremor in PD and ET. Effects on dystonic tremor were
      modest and transient. CLASSIFICATION OF EVIDENCE: This provides Class IV
      evidence. It is an observational study.

PMID- 28768841
TI  - Association of parathyroid hormone with 20-year cognitive decline: The ARIC
      study.
AB  - OBJECTIVE: We hypothesized that elevated parathyroid hormone (PTH) levels will be
      independently associated with 20-year cognitive decline in a large population
      based cohort. METHODS: We studied 12,964 middle-aged white and black ARIC
      participants without a history of prior stroke who, in 1990-1992 (baseline), had
      serum PTH levels measured and cognitive function testing, with repeat cognitive
      testing performed at up to 2 follow-up visits. Cognitive testing included the
      Delayed Word Recall, the Digit Symbol Substitution, and the Word Fluency tests,
      which were summed as a global Z score. Using mixed-effects models, we compared
      the relative decline in individual and global cognitive scores between each of
      the top 3 quartiles of PTH levels to the reference bottom quartile. We adjusted
      for demographic variables, education, vascular risk factors, and levels of
      calcium, phosphate, and vitamin D. We imputed missing covariate and follow-up
      cognitive data to account for attrition. RESULTS: The mean (SD) age of our cohort
      was 57 (6) years, 57% were women, and 24% were black. There was no cross
      sectional association of elevated PTH with cognitive global Z score at baseline
      (p > 0.05). Over a median of 20.7 years, participants in each PTH quartile showed
      a decline in cognitive function. However, there was no significant difference in
      cognitive decline between each of the top 3 quartiles and the lowest reference
      quartile (p > 0.05). In a subset, there was also no association of higher mid
      life PTH levels with late-life prevalent adjudicated dementia (p > 0.05).
      CONCLUSIONS: Our work does not support an independent influence of PTH on
      cognitive decline in this population-based cohort study.

PMID- 28768842
TI  - Developing an outline for teleneurology curriculum: AAN Telemedicine Work Group
      recommendations.
AB  - The emerging field of teleneurology is delivering quality care to neurologic
      patients in increasingly numerous technologies and configurations. Teleneurology
      is well-positioned to address many of the logistical issues neurologists and
      their patients encounter today. However, formalized medical training has not
      caught up with this developing field, and there is a lack of formal education
      concentrating on the specific opportunities and challenges of teleneurology.
      Considering this, the American Academy of Neurology Telemedicine Work Group
      identified equivalencies with which any practitioner of teleneurology should be
      familiar. The purpose of this curriculum is not to define teleneurology or
      mandate where its use is appropriate, but rather to provide guidance on basic
      equivalencies that students, residents, and practitioners should know while
      practicing teleneurology. Comprehensive training in clinical bedside neurology is
      necessary to safely practice teleneurology and the components of this curriculum
      are an extension of that training. In this article, we offer a detailed
      discussion on the rationale for the contents of this curriculum and conclude by
      providing a model curriculum and an outline for evaluating residents in
      teleneurology.

PMID- 28768843
TI  - Individualized risk prediction of major bleeding in secondary stroke prevention:
      Are we there yet?

PMID- 28768845
TI  - Sudden unexpected death in epilepsy patients is often misdiagnosed as sudden
      cardiac death.

PMID- 28768844
TI  - Prognostic relevance of MOG antibodies in children with an acquired demyelinating
      syndrome.
AB  - OBJECTIVE: To assess the prognostic value of MOG antibodies (abs) in the
      differential diagnosis of acquired demyelinating syndromes (ADS). METHODS:
      Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands
      (OCB) in children with ADS and 24 months of follow-up were reviewed in this
      observational prospective multicenter hospital-based study. RESULTS: Two hundred
      ten children with ADS were included and diagnosed with acute disseminated
      encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD)
      (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis
      (MS) (n = 37) after the first episode. MOG-abs were predominantly found in ADEM
      (57%) and less frequently in NMOSD (25%), CIS (25%), or MS (8%). Increased MOG-ab
      titers were associated with younger age (p = 0.0001), diagnosis of ADEM (p =
      0.005), increased CSF cell counts (p = 0.011), and negative OCB (p = 0.012). At
      24-month follow-up, 96 children had no further relapses. Thirty-five children
      developed recurrent non-MS episodes (63% MOG-, 17% AQP4-abs at onset). Seventy
      nine children developed MS (4% MOG-abs at onset). Recurrent non-MS episodes were
      associated with high MOG-ab titers (p = 0.0003) and older age at onset (p =
      0.024). MS was predicted by MS-like MRI (p < 0.0001) and OCB (p = 0.007). An MOG
      ab cutoff titer >=1:1,280 predicted a non-MS course with a sensitivity of 47% and
      a specificity of 100% and a recurrent non-MS course with a sensitivity of 46% and
      a specificity of 86%. CONCLUSIONS: Our results show that the presence of MOG-abs
      strongly depends on the age at disease onset and that high MOG-ab titers were
      associated with a recurrent non-MS disease course.

PMID- 28768846
TI  - Clinical phenotype and outcome of hepatitis E virus-associated neuralgic
      amyotrophy.
AB  - OBJECTIVE: To determine the clinical phenotype and outcome in hepatitis E virus
      associated neuralgic amyotrophy (HEV-NA). METHODS: Cases of NA were identified in
      11 centers from 7 European countries, with retrospective analysis of
      demographics, clinical/laboratory findings, and treatment and outcome. Cases of
      HEV-NA were compared with NA cases without evidence of HEV infection. RESULTS:
      Fifty-seven cases of HEV-NA and 61 NA cases without HEV were studied. Fifty-six
      of 57 HEV-NA cases were anti-HEV IgM positive; 53/57 were IgG positive. In 38
      cases, HEV RNA was recovered from the serum and in 1 from the CSF (all genotype
      3). Fifty-one of 57 HEV-NA cases were anicteric; median alanine aminotransferase
      259 IU/L (range 12-2,961 IU/L); in 6 cases, liver function tests were normal. HEV
      NA cases were more likely to have bilateral involvement (80.0% vs 8.6%, p <
      0.001), damage outside the brachial plexus (58.5% vs 10.5%, p < 0.01), including
      phrenic nerve and lumbosacral plexus injury (25.0% vs 3.5%, p = 0.01, and 26.4%
      vs 7.0%, p = 0.001), reduced reflexes (p = 0.03), sensory symptoms (p = 0.04)
      with more extensive damage to the brachial plexus. There was no difference in
      outcome between the 2 groups at 12 months. CONCLUSIONS: Patients with HEV-NA are
      usually anicteric and have a distinct clinical phenotype, with predominately
      bilateral asymmetrical involvement of, and more extensive damage to, the brachial
      plexus. Involvement outside the brachial plexus is more common in HEV-NA. The
      relationship between HEV and NA is likely to be causal, but is easily overlooked.
      Patients presenting with NA should be tested for HEV, irrespective of liver
      function test results. Prospective treatment/outcome studies of HEV-NA are
      warranted.

PMID- 28768847
TI  - Cross-sectional analysis of a large cohort with X-linked Charcot-Marie-Tooth
      disease (CMTX1).
AB  - OBJECTIVE: To extend the phenotypic description of Charcot-Marie-Tooth disease
      (CMTX1) and to draw new genotype-phenotype relationships. METHODS: Mutations in
      GJB1 cause the main X-linked form of CMTX (CMTX1). We report cross-sectional data
      from 160 patients (from 120 different families, with 89 different mutations) seen
      at the Inherited Neuropathies Consortium centers. RESULTS: We evaluated 87 males
      who had a mean age of 41 years (range 10-78 years) and 73 females who had a mean
      age of 46 years (range 15-84 years). Sensory-motor polyneuropathy affects both
      sexes, more severely in males than in females, and there was a strong correlation
      between age and disease burden in males but not in females. Compared with
      females, males had more severe reduction in motor and sensory neurophysiology
      parameters. In contrast to females, the radial nerve sensory response in older
      males tended to be more severely affected compared with younger males. Median and
      ulnar nerve motor amplitudes were also more severely affected in older males,
      whereas ulnar nerve motor potentials tended to be more affected in older females.
      Conversely, there were no statistical differences between the sexes in other
      features of the disease, such as problems with balance and hand dexterity.
      CONCLUSIONS: In the absence of a phenotypic correlation with specific GJB1
      mutations, sex-specific distinctions and clinically relevant attributes need to
      be incorporated into the measurements for clinical trials in people with CMTX1.
      CLINICALTRIALSGOV IDENTIFIER: NCT01193075.

PMID- 28768849
TI  - Brain imaging in myotonic dystrophy type 1: A systematic review.
AB  - OBJECTIVE: To systematically review brain imaging studies in myotonic dystrophy
      type 1 (DM1). METHODS: We searched Embase (index period 1974-2016) and MEDLINE
      (index period 1946-2016) for studies in patients with DM1 using MRI, magnetic
      resonance spectroscopy (MRS), functional MRI (fMRI), CT, ultrasound, PET, or
      SPECT. From 81 studies, we extracted clinical characteristics, primary outcomes,
      clinical-genetic correlations, and information on potential risk of bias. Results
      were summarized and pooled prevalence of imaging abnormalities was calculated,
      where possible. RESULTS: In DM1, various imaging changes are widely dispersed
      throughout the brain, with apparently little anatomical specificity. We found
      general atrophy and widespread gray matter volume reductions in all 4 cortical
      lobes, the basal ganglia, and cerebellum. The pooled prevalence of white matter
      hyperintensities is 70% (95% CI 64-77), compared with 6% (95% CI 3-12) in
      unaffected controls. DTI shows increased mean diffusivity in all 4 lobes and
      reduced fractional anisotropy in virtually all major association, projection, and
      commissural white matter tracts. Functional studies demonstrate reduced glucose
      uptake and cerebral perfusion in frontal, parietal, and temporal lobes, and
      abnormal fMRI connectivity patterns that correlate with personality traits. There
      is significant between-study heterogeneity in terms of imaging methods, which
      together with the established clinical variability of DM1 may explain divergent
      results. Longitudinal studies are remarkably scarce. CONCLUSIONS: DM1 brains show
      widespread white and gray matter involvement throughout the brain, which is
      supported by abnormal resting-state network, PET/SPECT, and MRS parameters.
      Longitudinal studies evaluating spatiotemporal imaging changes are essential.

PMID- 28768850
TI  - Five cases of malignant melanoma during fingolimod treatment in Dutch patients
      with MS.

PMID- 28768851
TI  - Underestimation of sudden deaths among patients with seizures and epilepsy.
AB  - OBJECTIVE: To determine the definite and potential frequency of seizures and
      epilepsy as a cause of death (COD) and how often this goes unrecognized. METHODS:
      Prospective determination of seizures or epilepsy and final COD for individuals
      aged 18-90 years with out-of-hospital sudden cardiac deaths (SCDs) from the
      population-based San Francisco POST SCD Study. We compared prospective seizure or
      epilepsy diagnosis and final COD as adjudicated by a multidisciplinary committee
      (pathologists, electrophysiologists, and a vascular neurologist) vs retrospective
      adjudication by 2 epileptologists with expertise in seizure-related mortality.
      RESULTS: Of 541 SCDs identified during the 37-month study period (mean age 62.8
      years, 69% men), 525 (97%) were autopsied; 39/525 (7.4%) had seizures or epilepsy
      (mean age: 58 years, range: 27-92; 67% men), comprising 17% of 231 nonarrhythmic
      sudden deaths. The multidisciplinary team identified 15 cases of epilepsy, 6
      sudden unexpected deaths in epilepsy (SUDEPs), and no deaths related to acute
      symptomatic seizures. The epileptologists identified 25 cases of epilepsy and 8
      definite SUDEPs, 10 possible SUDEPs, and 5 potential cases of acute symptomatic
      seizures as a COD. CONCLUSIONS: Among the 25 patients identified with epilepsy by
      the epileptologists, they found definite or possible SUDEP in 72% (18/25) vs 24%
      (6/25) by the multidisciplinary group (6/15 cases they identified with epilepsy).
      The epileptologists identified acute symptomatic seizures as a potential COD in
      5/14 patients with alcohol-related seizures. Epilepsy is underdiagnosed among
      decedents. Among patients with seizures and epilepsy who die suddenly, seizures
      and SUDEP often go unrecognized as a potential or definite COD.

PMID- 28768848
TI  - Predicting major bleeding in patients with noncardioembolic stroke on
      antiplatelets: S2TOP-BLEED.
AB  - OBJECTIVE: To develop and externally validate a prediction model for major
      bleeding in patients with a TIA or ischemic stroke on antiplatelet agents.
      METHODS: We combined individual patient data from 6 randomized clinical trials
      (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet
      therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial
      were performed to study the association between predictors and major bleeding. A
      risk prediction model was derived and validated in the PERFORM trial. Performance
      was assessed with the c statistic and calibration plots. RESULTS: Major bleeding
      occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up.
      The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI]
      4.4%-4.9%). Predictors were male sex, smoking, type of antiplatelet agents
      (aspirin-clopidogrel), outcome on modified Rankin Scale >=3, prior stroke, high
      blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes
      (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60-0.64)
      and showed good calibration in the development data. Major bleeding risk ranged
      from 2% in patients aged 45-54 years without additional risk factors to more than
      10% in patients aged 75-84 years with multiple risk factors. In external
      validation, the model had a c statistic of 0.61 (95% CI 0.59-0.63) and slightly
      underestimated major bleeding risk. CONCLUSIONS: The S2TOP-BLEED score can be
      used to estimate 3-year major bleeding risk in patients with a TIA or ischemic
      stroke who use antiplatelet agents, based on readily available characteristics.
      The discriminatory performance may be improved by identifying stronger predictors
      of major bleeding.

PMID- 28768852
TI  - Septic Episodes in a Premature Infant After In Utero Exposure to Rituximab.
AB  - Rituximab is an increasingly used immunotherapeutic agent for women of
      reproductive age for treatment of autoimmune diseases, leukemias, and lymphomas.
      Rituximab is a chimeric monoclonal antibody that targets B-cell surface antigen
      CD20 and can cross the placenta. Current evidence of the impact of this
      medication on the developing fetus is limited, but there is little to suggest
      that fetal exposure to this medication places an infant at increased risk of
      immunosuppression and subsequent infection. Here we report a case of in utero
      rituximab exposure that was associated with 2 severe septic episodes with
      Enterococcus faecalis, in a premature infant of 29 weeks' gestational age with a
      birth weight of 820 g. The patient had a critically depressed B-lymphocyte subset
      of 10% and undetectable immunoglobulin (Ig)G, IgM, and IgA levels at 37 weeks'
      postmenstrual age. Interestingly, both episodes of sepsis coincided with
      transition from donor human milk to formula feeds. She was treated with
      intravenous immunoglobulin, antibiotics, and donor human milk. We postulate that
      placental transfer of rituximab, prematurity, and the low levels of protective
      maternal antibodies increased the susceptibility of this patient to sepsis by E
      faecalis, a resident of the normal gut flora, whereas the secretory IgA in donor
      human milk may have played a protective role.

PMID- 28768853
TI  - Vaccine-Preventable Diseases Requiring Hospitalization.
AB  - BACKGROUND: Plain children often have lower immunization rates than non-Plain
      children. Penn State Health Children's Hospital is a tertiary medical center with
      large nearby Plain (Amish and Mennonite) communities. We sought to describe the
      characteristics of children hospitalized with vaccine-preventable diseases
      (VPDs). We hypothesized that Amish children would have a higher risk of VPDs than
      non-Amish children. METHODS: International Classification of Diseases, Ninth
      Revision codes were used to identify patients <18 years diagnosed with a VPD from
      January 1, 2005, to December 31, 2015, at Penn State Children's Hospital.
      Demographic information, immunization status, and outcomes were obtained from
      medical records. By using the number of children in our primary service area, we
      calculated the risk of VPD requiring hospitalization for Amish and non-Amish
      children. We assessed the relationship between Plain affiliation and vaccination
      status by using the Pearson correlation coefficient. RESULTS: There were 215
      children with 221 VPDs. Most occurred in non-Plain children: 179 of 221 (81%).
      Except for pneumococcal infections, VPD occurred mostly in unvaccinated or
      immunocompromised children, regardless of Plain affiliation. There were 15
      Haemophilus influenzae type b and 5 tetanus infections that occurred in children
      with an unvaccinated or unknown vaccination status. The risk of a VPD requiring
      hospitalization was greater for Amish than for non-Plain children (risk ratio:
      2.67 [95% confidence interval: 1.87-3.82]). There was a strong correlation
      between Plain affiliation and lack of vaccination (r = -0.63, P < .01).
      CONCLUSIONS: Amish children had an increased risk of a VPD requiring
      hospitalization than non-Plain children. With the exception of those with
      pneumococcal disease, most vaccinated children hospitalized with a VPD were
      immunocompromised.

PMID- 28768854
TI  - Presence of a Shared 5'-Leader Sequence in Ancestral Human and Mammalian
      Retroviruses and Its Transduction into Feline Leukemia Virus.
AB  - Recombination events induce significant genetic changes, and this process can
      result in virus genetic diversity or in the generation of novel pathogenicity. We
      discovered a new recombinant feline leukemia virus (FeLV) gag gene harboring an
      unrelated insertion, termed the X region, which was derived from Felis catus
      endogenous gammaretrovirus 4 (FcERV-gamma4). The identified FcERV-gamma4
      proviruses have lost their coding capabilities, but some can express their viral
      RNA in feline tissues. Although the X-region-carrying recombinant FeLVs appeared
      to be replication-defective viruses, they were detected in 6.4% of tested FeLV
      infected cats. All isolated recombinant FeLV clones commonly incorporated a
      middle part of the FcERV-gamma4 5'-leader region as an X region. Surprisingly, a
      sequence corresponding to the portion contained in all X regions is also present
      in at least 13 endogenous retroviruses (ERVs) observed in the cat, human,
      primate, and pig genomes. We termed this shared genetic feature the commonly
      shared (CS) sequence. Despite our phylogenetic analysis indicating that all CS
      sequence-carrying ERVs are classified as gammaretroviruses, no obvious closeness
      was revealed among these ERVs. However, the Shannon entropy in the CS sequence
      was lower than that in other parts of the provirus genome. Notably, the CS
      sequence of human endogenous retrovirus T had 73.8% similarity with that of FcERV
      gamma4, and specific signals were detected in the human genome by Southern blot
      analysis using a probe for the FcERV-gamma4 CS sequence. Our results provide an
      interesting evolutionary history for CS-sequence circulation among several
      distinct ancestral viruses and a novel recombined virus over a prolonged
      period.IMPORTANCE Recombination among ERVs or modern viral genomes causes a rapid
      evolution of retroviruses, and this phenomenon can result in the serious
      situation of viral disease reemergence. We identified a novel recombinant FeLV
      gag gene that contains an unrelated sequence, termed the X region. This region
      originated from the 5' leader of FcERV-gamma4, a replication-incompetent feline
      ERV. Surprisingly, a sequence corresponding to the X region is also present in
      the 5' portion of other ERVs, including human endogenous retroviruses. Scattered
      copies of the ERVs carrying the unique genetic feature, here named the commonly
      shared (CS) sequence, were found in each host genome, suggesting that ancestral
      viruses may have captured and maintained the CS sequence. More recently, a novel
      recombinant FeLV hijacked the CS sequence from inactivated FcERV-gamma4 as the X
      region. Therefore, tracing the CS sequences can provide unique models for not
      only the modern reservoir of new recombinant viruses but also the genetic
      features shared among ancient retroviruses.

PMID- 28768855
TI  - Inactivated H7 Influenza Virus Vaccines Protect Mice despite Inducing Only Low
      Levels of Neutralizing Antibodies.
AB  - Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a
      significant public health threat, as evidenced by the ongoing outbreak of human
      A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI)
      and microneutralization (MN) assays, H7 viruses and vaccines are found to induce
      lower level of neutralizing antibodies (nAb) than do their seasonal counterparts,
      making it difficult to develop and evaluate prepandemic vaccines. We have
      previously shown that purified recombinant H7 HA appear to be poorly immunogenic
      in that they induce low levels of HI and MN antibodies. In this study, we
      immunized mice with whole inactivated reverse genetics reassortant (RG) viruses
      expressing HA and neuraminidase (NA) from 3 different H7 viruses
      [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New
      York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or
      A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies
      to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However,
      the antibody titers induced by H7 viruses were significantly lower when measured
      by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines
      conferred complete protection against homologous virus challenge in mice, and the
      serum antibodies directed against the HA head region were capable of mediating
      protection. The apparently low immunogenicity associated with H7 viruses and
      vaccines may be at least partly related to measuring antibody titers with the
      traditional HI and MN assays, which may not provide a true measure of protective
      immunity associated with H7 immunization. This study underscores the need for
      development of additional correlates of protection for prepandemic
      vaccines.IMPORTANCE H7 avian influenza viruses present a serious risk to human
      health. Preparedness efforts include development of prepandemic vaccines. For
      seasonal influenza viruses, protection is correlated with antibody titers
      measured by hemagglutination inhibition (HI) and virus microneutralization (MN)
      assays. Since H7 vaccines typically induce low titers in HI and MN assays, they
      have been considered to be poorly immunogenic. We show that in mice H7 whole
      inactivated virus vaccines (WIVs) were as immunogenic as seasonal WIVs, as they
      induced similar levels of overall serum antibodies. However, a larger fraction of
      the antibodies induced by H7 WIV was nonneutralizing in vitro Nevertheless, the
      H7 WIV completely protected mice against homologous viral challenge, and
      antibodies directed against the HA head were the major contributor toward immune
      protection. Vaccines against H7 avian influenza viruses may be more effective
      than HI and virus neutralization assays suggest, and such vaccines may need other
      methods for evaluation.

PMID- 28768856
TI  - Nonencapsidated 5' Copy-Back Defective Interfering Genomes Produced by
      Recombinant Measles Viruses Are Recognized by RIG-I and LGP2 but Not MDA5.
AB  - Attenuated measles virus (MV) is one of the most effective and safe vaccines
      available, making it an attractive candidate vector for preventing other
      infectious diseases. Yet the great capacity of this vaccine still needs to be
      understood at the molecular level. MV vaccine strains have different type I
      interferon (IFN)-inducing abilities that partially depend on the presence of 5'
      copy-back defective interfering genomes (DI-RNAs). DI-RNAs are pathogen
      associated molecular patterns recognized by RIG-I-like receptors (RLRs) (RIG-I,
      MDA5, and LGP2) that activate innate immune signaling and shape the adaptive
      immune response. In this study, we characterized the DI-RNAs produced by various
      modified recombinant MVs (rMVs), including vaccine candidates, as well as wild
      type MV. All tested rMVs produced 5' copy-back DI-RNAs that were different in
      length and nucleotide sequence but still respected the so-called "rule of six."
      We correlated the presence of DI-RNAs with a larger stimulation of the IFN-beta
      pathway and compared their immunostimulatory potentials. Importantly, we revealed
      that encapsidation of DI-RNA molecules within the MV nucleocapsid abolished their
      immunoactive properties. Furthermore, we identified specific interactions of DI
      RNAs with both RIG-I and LGP2 but not MDA5. Our results suggest that DI-RNAs
      produced by rMV vaccine candidates may indeed strengthen their efficiency by
      triggering RLR signaling.IMPORTANCE Having been administered to hundreds of
      millions of children, the live attenuated measles virus (MV) vaccine is the
      safest and most widely used human vaccine, providing high protection with long
      term memory. Additionally, recombinant MVs carrying heterologous antigens are
      promising vectors for new vaccines. The great capacity of this vaccine still
      needs to be elucidated at the molecular level. Here we document that recombinant
      MVs produce defective interfering genomes that have high immunostimulatory
      properties via their binding to RIG-I and LGP2 proteins, both of which are
      cytosolic nonself RNA sensors of innate immunity. Defective interfering genome
      production during viral replication should be considered of great importance due
      to the immunostimulatory properties of these genomes as intrinsic adjuvants
      produced by the vector that increase recognition by the innate immune system.

PMID- 28768857
TI  - Molecular Function Analysis of Rabies Virus RNA Polymerase L Protein by Using an
      L Gene-Deficient Virus.
AB  - While the RNA-dependent RNA polymerase L protein of rabies virus (RABV), a member
      of the genus Lyssavirus of the family Rhabdoviridae, has potential to be a
      therapeutic target for rabies, the molecular functions of this protein have
      remained largely unknown. In this study, to obtain a novel experimental tool for
      molecular function analysis of the RABV L protein, we established by using a
      reverse genetics approach an L gene-deficient RABV (Nishi-DeltaL/Nluc), which
      infects, propagates, and correspondingly produces NanoLuc luciferase in cultured
      neuroblastoma cells transfected to express the L protein. trans-Complementation
      with wild-type L protein, but not that with a functionally defective L protein
      mutant, efficiently supported luciferase production by Nishi-DeltaL/Nluc,
      confirming its potential for function analysis of the L protein. Based on the
      findings obtained from comprehensive genetic analyses of L genes from various
      RABV and other lyssavirus species, we examined the functional importance of a
      highly conserved L protein region at positions 1914 to 1933 by a trans
      complementation assay with Nishi-DeltaL/Nluc and a series of L protein mutants.
      The results revealed that the amino acid sequence at positions 1929 to 1933
      (NPYNE) is functionally important, and this was supported by other findings that
      this sequence is critical for binding of the L protein with its essential
      cofactor, P protein, and thus also for L protein's RNA polymerase activity. Our
      findings provide useful information for the development of an anti-RABV drug
      targeting the L-P protein interaction.IMPORTANCE To the best of our knowledge,
      this is the first report on the establishment of an L gene-deficient, reporter
      gene-expressing virus in all species of the order Mononegavirales, also
      highlighting its applicability to a trans-complementation assay, which is useful
      for molecular function analyses of their L proteins. Moreover, this study
      revealed for the first time that the NPYNE sequence at positions 1929 to 1933 in
      the RABV L protein is important for L protein's interaction with the P protein,
      consistent with and extending the results of a previous study showing that the P
      protein-binding domain in the L protein is located in its C-terminal region, at
      positions 1562 to 2127. This study indicates that the NPYNE sequence is a
      promising target for the development of an inhibitor of viral RNA synthesis,
      which has high potential as a therapeutic drug for rabies.

PMID- 28768858
TI  - Human Metapneumovirus M2-2 Protein Acts as a Negative Regulator of Alpha
      Interferon Production by Plasmacytoid Dendritic Cells.
AB  - Human metapneumovirus (HMPV) has the ability to inhibit Toll-like receptor 7
      (TLR7)- and TLR9-dependent alpha interferon (IFN-alpha) production by
      plasmacytoid dendritic cells (pDCs). However, the inhibition mechanism remains
      largely unknown. To identify viral proteins responsible for this inhibition, we
      performed a screening of HMPV open reading frames (ORFs) for the ability to block
      TLR7/9-dependent signaling reconstituted in HEK293T cells by transfection with
      myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor
      associated factor 6 (TRAF6), IKKalpha, and IFN regulatory factor 7 (IRF7). This
      screening demonstrated that the M2-2 protein was the most potent inhibitor of
      TLR7/9-dependent IFN-alpha induction. A recombinant HMPV in which the M2-2 ORF
      was silenced indeed induced greater IFN-alpha production by human pDCs than wild
      type HMPV did. Immunoprecipitation experiments showed direct physical association
      of the M2-2 protein with the inhibitory domain (ID) of IRF7. As a natural
      consequence of this, transfection of IRF7 lacking the ID, a constitutively active
      mutant, resulted in activation of the IFN-alpha promoter even in the presence of
      M2-2. Bioluminescence resonance energy transfer assays and split Renilla
      luciferase complementation assays revealed that M2-2 inhibited
      MyD88/TRAF6/IKKalpha-induced homodimerization of IRF7. In contrast, expression of
      the M2-2 protein did not result in inhibition of IPS-1-induced homodimerization
      and resultant activation of IRF7. This indicates that inhibition of
      MyD88/TRAF6/IKKalpha-induced IRF7 homodimerization does not result from a steric
      effect of M2-2 binding. Instead, it was found that M2-2 inhibited
      MyD88/TRAF6/IKKalpha-induced phosphorylation of IRF7 on Ser477. These results
      suggest that M2-2 blocks TLR7/9-dependent IFN-alpha induction by preventing IRF7
      homodimerization, possibly through its effects on the phosphorylation status of
      IRF7.IMPORTANCE The family Paramyxoviridae is divided into two subfamilies, the
      Paramyxovirinae and the Pneumovirinae Members of the subfamily Paramyxovirinae
      have the ability to inhibit TLR7/9-dependent IFN-alpha production, and the
      underlying inhibition mechanism has been intensively studied. In contrast, little
      is known about how members of the subfamily Pneumovirinae regulate IFN-alpha
      production by pDCs. We identified the M2-2 protein of HMPV, a member of the
      subfamily Pneumovirinae, as a negative regulator of IFN-alpha production by pDCs
      and uncovered the underlying mechanism. This study explains in part why the M2-2
      knockout recombinant HMPV is attenuated and further suggests that M2-2 is a
      potential target for HMPV therapy.

PMID- 28768859
TI  - Identification of Emerging Macrophage-Tropic HIV-1 R5 Variants in Brain Tissue of
      AIDS Patients without Severe Neurological Complications.
AB  - Untreated HIV-positive (HIV-1+) individuals frequently suffer from HIV-associated
      neurocognitive disorders (HAND), with about 30% of AIDS patients suffering severe
      HIV-associated dementias (HADs). Antiretroviral therapy has greatly reduced the
      incidence of HAND and HAD. However, there is a continuing problem of milder
      neurocognitive impairments in treated HIV+ patients that may be increasing with
      long-term therapy. In the present study, we investigated whether envelope (env)
      genes could be amplified from proviral DNA or RNA derived from brain tissue of 12
      individuals with normal neurology or minor neurological conditions (N/MC
      individuals). The tropism and characteristics of the brain-derived Envs were then
      investigated and compared to those of Envs derived from immune tissue. We showed
      that (i) macrophage-tropic R5 Envs could be detected in the brain tissue of 4/12
      N/MC individuals, (ii) macrophage-tropic Envs in brain tissue formed
      compartmentalized clusters distinct from non-macrophage-tropic (non-mac-tropic)
      Envs recovered from the spleen or brain, (iii) the evidence was consistent with
      active viral expression by macrophage-tropic variants in the brain tissue of some
      individuals, and (iv) Envs from immune tissue of the N/MC individuals were nearly
      all tightly non-mac-tropic, contrasting with previous data for neuro-AIDS
      patients where immune tissue Envs mediated a range of macrophage infectivities,
      from background levels to modest infection, with a small number of Envs from some
      patients mediating high macrophage infection levels. In summary, the data
      presented here show that compartmentalized and active macrophage-tropic HIV-1
      variants are present in the brain tissue of individuals before neurological
      disease becomes overt or serious.IMPORTANCE The detection of highly
      compartmentalized macrophage-tropic R5 Envs in the brain tissue of HIV patients
      without serious neurological disease is consistent with their emergence from a
      viral population already established there, perhaps from early disease. The
      detection of active macrophage-tropic virus expression, and probably replication,
      indicates that antiretroviral drugs with optimal penetration through the blood
      brain barrier should be considered even for patients without neurological disease
      (neuro-disease). Finally, our data are consistent with the brain forming a
      sanctuary site for latent virus and low-level viral replication in the absence of
      neuro-disease.

PMID- 28768860
TI  - Zinc Finger-Containing Cellular Transcription Corepressor ZBTB25 Promotes
      Influenza Virus RNA Transcription and Is a Target for Zinc Ejector Drugs.
AB  - Influenza A virus (IAV) replication relies on an intricate interaction between
      virus and host cells. How the cellular proteins are usurped for IAV replication
      remains largely obscure. The aim of this study was to search for novel and
      potential cellular factors that participate in IAV replication. ZBTB25, a
      transcription repressor of a variety of cellular genes, was identified by an RNA
      interference (RNAi) genomic library screen. Depletion of ZBTB25 significantly
      reduced IAV production. Conversely, overexpression of ZBTB25 enhanced it. ZBTB25
      interacted with the viral RNA-dependent RNA polymerase (RdRp) protein and
      modulated its transcription activity. In addition, ZBTB25 also functioned as a
      viral RNA (vRNA)-binding protein, binding preferentially to the U-rich sequence
      within the 5' untranslated region (UTR) of vRNA. Both protein-protein and protein
      RNA interactions involving ZBTB25 facilitated viral RNA transcription and
      replication. In addition, ZBTB25 suppressed interferon production, further
      enhancing viral replication. ZBTB25-associated functions required an intact zinc
      finger domain and posttranslational SUMO-1 modification of ZBTB25. Furthermore,
      treatment with disulfiram (a zinc ejector) of ZBTB25-overexpressing cells showed
      significantly reduced IAV production as a result of reduced RNA synthesis. Our
      findings indicate that IAV usurps ZBTB25 for IAV RNA synthesis and serves as a
      novel and potential therapeutic antiviral target.IMPORTANCE IAV-induced seasonal
      influenza causes severe illness and death in high-risk populations. However, IAV
      has developed resistance to current antiviral drugs due to its high mutation
      rate. Therefore, development of drugs targeting cellular factors required for IAV
      replication is an attractive alternative for IAV therapy. Here, we discovered a
      cellular protein, ZBTB25, that enhances viral RdRp activity by binding to both
      viral RdRp and viral RNA to stimulate viral RNA synthesis. A unique feature of
      ZBTB25 in the regulation of viral replication is its dual transcription
      functions, namely, promoting viral RNA transcription through binding to the U
      rich region of vRNA and suppressing cellular interferon production. ZBTB25
      contains a zinc finger domain that is required for RNA-inhibitory activity by
      chelating zinc ions. Disulfiram treatment disrupts the zinc finger functions,
      effectively repressing IAV replication. Based on our findings, we demonstrate
      that ZBTB25 regulates IAV RNA transcription and replication and serves as a
      promising antiviral target for IAV treatment.

PMID- 28768861
TI  - Positive and Negative Regulation of Type I Interferons by the Human T Cell
      Leukemia Virus Antisense Protein HBZ.
AB  - The pathogenesis of human T cell leukemia virus type 1 (HTLV-1) is strongly
      linked to the viral regulatory proteins Tax1 and HBZ, whose opposing functions
      contribute to the clinical outcome of infection. Type I interferons alpha and
      beta (IFN-alpha and IFN-beta) are key cytokines involved in innate immunity, and
      IFN-alpha, in combination with other antivirals, is extensively used in the
      treatment of HTLV-1 infection. The relationship between HTLV-1 and IFN signaling
      is unclear, and to date the effect of HBZ on this pathway has not been examined.
      Here we report that HBZ significantly enhances interferon regulatory factor 7
      (IRF7)-induced IFN-alpha- and IFN-stimulated response element (ISRE) promoter
      activities and IFN-alpha production and can counteract the inhibitory effect of
      Tax1. In contrast to this, we show that HBZ and Tax1 cooperate to inhibit the
      induction of IFN-beta and ISRE promoters by IRF3 and IFN-beta production. In
      addition, we reveal that HBZ enhances ISRE activation by IFN-alpha. We further
      show that HBZ enhances IRF7 and suppresses IRF3 activation by TBK1 and
      IKKepsilon. We demonstrate that HBZ has no effect on virus-induced nuclear
      accumulation of IRF3, suggesting that it may inhibit IRF3 activity at a
      transcriptional level. We show that HBZ physically interacts with IRF7 and
      IKKepsilon but not with IRF3 or TBK1. Overall, our findings suggest that both HBZ
      and Tax1 are negative regulators of immediate early IFN-beta innate immune
      responses, while HBZ but not Tax1 positively regulates the induction of IFN-alpha
      and downstream IFN-alpha signaling.IMPORTANCE Type I interferons are powerful
      antiviral cytokines and are used extensively in the treatment of HTLV-1-induced
      adult T cell leukemia (ATL). To date, the relationship between HTLV-1 and the IFN
      pathway is poorly understood, and studies so far have focused on Tax1. Our study
      is unique in that it examined the effect of HBZ, alone or in combination with
      Tax1, on type I IFN signaling. This is important because HBZ is frequently the
      only viral protein expressed in infected cells, particularly at later stages of
      infection. A better understanding of the how HBZ regulates IFN signaling may lead
      to the development of therapeutics that can modify such responses and improve the
      clinical outcome for infected individuals.

PMID- 28768862
TI  - Crystal Structure of the N-Terminal Half of the Traffic Controller UL37 from
      Herpes Simplex Virus 1.
AB  - Inner tegument protein UL37 is conserved among all three subfamilies of
      herpesviruses. Studies of UL37 homologs from two alphaherpesviruses, herpes
      simplex virus 1 (HSV-1) and pseudorabies virus (PRV), have suggested that UL37
      plays an essential albeit poorly defined role in intracellular capsid
      trafficking. At the same time, HSV and PRV homologs cannot be swapped, which
      suggests that in addition to a conserved function, UL37 homologs also have
      divergent virus-specific functions. Accurate dissection of UL37 functions
      requires detailed maps in the form of atomic-resolution structures. Previously,
      we reported the crystal structure of the N-terminal half of UL37 (UL37N) from
      PRV. Here, we report the crystal structure of HSV-1 UL37N. Comparison of the two
      structures reveals that UL37 homologs differ in their overall shapes,
      distributions of surface charges, and locations of projecting loops. In contrast,
      the previously identified R2 surface region is structurally conserved. We propose
      that within the N-terminal half of UL37, functional conservation is centered
      within the R2 surface region, whereas divergent structural elements pinpoint
      regions mediating virus-specific functions and may engage different binding
      partners. Together, the two structures can now serve as templates for a structure
      guided exploration of both conserved and virus-specific functions of
      UL37.IMPORTANCE The ability to move efficiently within host cell cytoplasm is
      essential for replication in all viruses. It is especially important in the
      neuroinvasive alphaherpesviruses, such as human herpes simplex virus 1 (HSV-1),
      HSV-2, and veterinarian pseudorabies virus (PRV), that infect the peripheral
      nervous system and have to travel long distances along axons. Capsid movement in
      these viruses is controlled by capsid-associated tegument proteins, yet their
      specific roles have not yet been defined. Systematic exploration of the roles of
      tegument proteins in capsid trafficking requires detailed navigational charts in
      the form of their three-dimensional structures. Here, we determined the crystal
      structure of the N-terminal half of a conserved tegument protein, UL37, from HSV
      1. This structure, along with our previously reported structure of the UL37
      homolog from PRV, provides a much needed 3-dimensional template for the
      dissection of both conserved and virus-specific functions of UL37 in
      intracellular capsid trafficking.

PMID- 28768863
TI  - HRAS, EGFR, MET, and RON Genes Are Recurrently Activated by Provirus Insertion in
      Liver Tumors Induced by the Retrovirus Myeloblastosis-Associated Virus 2.
AB  - Myeloblastosis-associated virus 2 (MAV-2) is a highly tumorigenic simple avian
      retrovirus. Chickens infected in ovo with MAV-2 develop tumors in the kidneys,
      lungs, and liver with a short latency, less than 8 weeks. Here we report the
      results of molecular analyses of MAV-2-induced liver tumors that fall into three
      classes: hepatic hemangiosarcomas (HHSs), intrahepatic cholangiocarcinomas
      (ICCs), and hepatocellular carcinomas (HCCs). Comprehensive inverse PCR-based
      screening of 92 chicken liver tumors revealed that in ca. 86% of these tumors,
      MAV-2 provirus had integrated into one of four gene loci: HRAS, EGFR, MET, and
      RON Insertionally mutated genes correlated with tumor type: HRAS was hit in HHSs,
      MET in ICCs, RON mostly in ICCs, and EGFR mostly in HCCs. The provirus insertions
      led to the overexpression of the affected genes and, in the case of EGFR and RON,
      also to the truncation of exons encoding the extracellular ligand-binding domains
      of these transmembrane receptors. The structures of truncated EGFR and RON
      closely mimic the structures of oncogenic variants of these genes frequently
      found in human tumors (EGFRvIII and sfRON).IMPORTANCE These data describe the
      mechanisms of oncogenesis induced in chickens by the MAV-2 retrovirus. They also
      show that molecular processes converting cellular regulatory genes to cancer
      genes may be remarkably similar in chickens and humans. We suggest that the MAV-2
      retrovirus-based model can complement experiments performed using mouse models
      and provide data that could translate to human medicine.

PMID- 28768864
TI  - Kinase Activity of Fibroblast Growth Factor Receptor 3 Regulates Activity of the
      Papillomavirus E2 Protein.
AB  - The papillomavirus (PV) E2 protein is a DNA binding, protein interaction platform
      that recruits viral and host factors necessary for transcription and replication.
      We recently discovered phosphorylation of a tyrosine (Y102) in bovine PV (BPV)
      E2. To identify the responsible factor, we tested several candidate tyrosine
      kinases that are highly expressed in keratinocytes for binding to BPV-1 E2.
      Fibroblast growth factor receptor 3 (FGFR3) coimmunoprecipitated with the BPV-1
      E2 protein, as did human papillomavirus 31 (HPV-31) E2, which also colocalized
      with FGFR3 within the nucleus. A constitutively active mutant form of FGFR3
      decreased BPV-1 and HPV-31 transient replication although this result also
      occurred in a BPV-1 E2 mutant lacking a previously identified phosphorylation
      site of interest (Y102). Furthermore, FGFR3 depletion in cell lines that maintain
      HPV-31 episomes increased viral copy number. These results suggest that FGFR3
      kinase activity may regulate the PV reproductive program through phosphorylation
      of the E2 protein although this is unlikely to occur through the Y102 residue of
      HPV E2.IMPORTANCE The papillomavirus (PV) is a double-stranded DNA tumor virus
      infecting cervix, mouth, and throat tissues. The viral protein E2 is responsible
      for the replication of the virus. Understanding the mechanisms of the replicative
      life cycle of the virus may bring to light direct targets and treatments against
      viral infection. We recently found that the fibroblast growth factor receptor 3
      (FGFR3) interacts with and mediates PV E2 function through phosphorylation of the
      E2 protein. Our study suggests that the function of the E2 protein may be
      regulated through a direct FGFR3 target during the maintenance stage of the PV
      life cycle.

PMID- 28768865
TI  - Ubiquitin Ligase WWP1 Interacts with Ebola Virus VP40 To Regulate Egress.
AB  - Ebola virus (EBOV) is a member of the Filoviridae family and the cause of
      hemorrhagic fever outbreaks. The EBOV VP40 (eVP40) matrix protein is the main
      driving force for virion assembly and budding. Indeed, expression of eVP40 alone
      in mammalian cells results in the formation and budding of virus-like particles
      (VLPs) which mimic the budding process and morphology of authentic, infectious
      EBOV. To complete the budding process, eVP40 utilizes its PPXY L-domain motif to
      recruit a specific subset of host proteins containing one or more modular WW
      domains that then function to facilitate efficient production and release of
      eVP40 VLPs. In this report, we identified additional host WW-domain interactors
      by screening for potential interactions between mammalian proteins possessing one
      or more WW domains and WT or PPXY mutant peptides of eVP40. We identified the
      HECT family E3 ubiquitin ligase WWP1 and all four of its WW domains as strong
      interactors with the PPXY motif of eVP40. The eVP40-WWP1 interaction was
      confirmed by both peptide pulldown and coimmunoprecipitation assays, which also
      demonstrated that modular WW domain 1 of WWP1 was most critical for binding to
      eVP40. Importantly, the eVP40-WWP1 interaction was found to be biologically
      relevant for VLP budding since (i) small interfering RNA (siRNA) knockdown of
      endogenous WWP1 resulted in inhibition of eVP40 VLP egress, (ii) coexpression of
      WWP1 and eVP40 resulted in ubiquitination of eVP40 and a subsequent increase in
      eVP40 VLP egress, and (iii) an enzymatically inactive mutant of WWP1 (C890A) did
      not ubiquitinate eVP40 or enhance eVP40 VLP egress. Last, our data show that
      ubiquitination of eVP40 by WWP1 enhances egress of VLPs and concomitantly
      decreases cellular levels of higher-molecular-weight oligomers of eVP40. In sum,
      these findings contribute to our fundamental understanding of the functional
      interplay between host E3 ligases, ubiquitination, and regulation of EBOV VP40
      mediated egress.IMPORTANCE Ebola virus (EBOV) is a high-priority, emerging human
      pathogen that can cause severe outbreaks of hemorrhagic fever with high mortality
      rates. As there are currently no approved vaccines or treatments for EBOV, a
      better understanding of the biology and functions of EBOV-host interactions that
      promote or inhibit viral budding is warranted. Here, we describe a physical and
      functional interaction between EBOV VP40 (eVP40) and WWP1, a host E3 ubiquitin
      ligase that ubiquitinates VP40 and regulates VLP egress. This viral PPXY-host WW
      domain-mediated interaction represents a potential new target for host-oriented
      inhibitors of EBOV egress.

PMID- 28768866
TI  - Reverse Engineering Field Isolates of Myxoma Virus Demonstrates that Some Gene
      Disruptions or Losses of Function Do Not Explain Virulence Changes Observed in
      the Field.
AB  - The coevolution of myxoma virus (MYXV) and wild European rabbits in Australia and
      Europe is a paradigm for the evolution of a pathogen in a new host species.
      Genomic analyses have identified the mutations that have characterized this
      evolutionary process, but defining causal mutations in the pathways from
      virulence to attenuation and back to virulence has not been possible. Using
      reverse genetics, we examined the roles of six selected mutations found in
      Australian field isolates of MYXV that fall in known or potential virulence
      genes. Several of these mutations occurred in genes previously identified as
      virulence genes in whole-gene knockout studies. Strikingly, no single or double
      mutation among the mutations tested had an appreciable impact on virulence. This
      suggests either that virulence evolution was defined by amino acid changes other
      than those analyzed here or that combinations of multiple mutations, possibly
      involving epistatic interactions or noncoding sequences, have been critical in
      the ongoing evolution of MYXV virulence. In sum, our results show that single
      gene knockout studies of a progenitor virus can have little power to predict the
      impact of individual mutations seen in the field. The genetic determinants
      responsible for this canonical case of virulence evolution remain to be
      determined.IMPORTANCE The species jump of myxoma virus (MYXV) from the South
      American tapeti to the European rabbit populations of Australia and Europe is a
      canonical example of host-pathogen coevolution. Detailed molecular studies have
      identified multiple genes in MYXV that are critical for virulence, and genome
      sequencing has revealed the evolutionary history of MYXV in Australia and Europe.
      However, it has not been possible to categorically identify the key mutations
      responsible for the attenuation of or reversion to virulence during this
      evolutionary process. Here we use reverse genetics to examine the role of
      mutations in viruses isolated early and late in the Australian radiation of MYXV.
      Surprisingly, none of the candidate mutations that we identified as likely having
      roles in attenuation proved to be important for virulence. This indicates that
      considerable caution is warranted when interpreting the possible role of
      individual mutations during virulence evolution.

PMID- 28768867
TI  - Mechanism of Interferon-Stimulated Gene Induction in HIV-1-Infected Macrophages.
AB  - Viruses manipulate the complex interferon and interferon-stimulated gene (ISG)
      system in different ways. We have previously shown that HIV inhibits type I and
      III interferons in its key target cells but directly stimulates a subset of >20
      ISGs in macrophages and dendritic cells, many of which are antiviral. Here, we
      examine the mechanism of induction of ISGs and show this occurs in two phases.
      The first phase was transient (0 to 24 h postinfection [hpi]), induced mainly by
      extracellular vesicles and one of its component proteins, HSP90alpha, contained
      within the HIV inoculum. The second, dominant, and persistent phase (>48 hpi) was
      induced via newly transcribed HIV RNA and sensed via RIGI, as shown by the
      reduction in ISG expression after the knockdown of the RIGI adaptor, MAVS, by
      small interfering RNA (siRNA) and the inhibition of both the initiation and
      elongation of HIV transcription by short hairpin RNA (shRNA) transcriptional
      silencing. We further define the induction pathway, showing sequential HIV RNA
      stimulation via Tat, RIGI, MAVS, IRF1, and IRF7, also identified by siRNA
      knockdown. IRF1 also plays a key role in the first phase. We also show that the
      ISGs IFIT1 to -3 inhibit HIV production, measured as extracellular infectious
      virus. All induced antiviral ISGs probably lead to restriction of HIV replication
      in macrophages, contributing to a persistent, noncytopathic infection, while the
      inhibition of interferon facilitates spread to adjacent cells. Both may influence
      the size of macrophage HIV reservoirs in vivo Elucidating the mechanisms of ISG
      induction may help in devising immunotherapeutic strategies to limit the size of
      these reservoirs.IMPORTANCE HIV, like other viruses, manipulates the antiviral
      interferon and interferon-stimulated gene (ISG) system to facilitate its initial
      infection and establishment of viral reservoirs. HIV specifically inhibits all
      type I and III interferons in its target cells, including macrophages, dendritic
      cells, and T cells. It also induces a subset of over 20 ISGs of differing
      compositions in each cell target. This occurs in two temporal phases in
      macrophages. Extracellular vesicles contained within the inoculum induce the
      first, transient phase of ISGs. Newly transcribed HIV RNA induce the second,
      dominant ISG phase, and here, the full induction pathway is defined. Therefore,
      HIV nucleic acids, which are potent inducers of interferon and ISGs, are
      initially concealed, and antiviral ISGs are not fully induced until replication
      is well established. These antiviral ISGs may contribute to persistent infection
      in macrophages and to the establishment of viral reservoirs in vivo.

PMID- 28768868
TI  - Asymmetric Trimeric Ring Structure of the Nucleocapsid Protein of Tospovirus.
AB  - Tomato spotted wilt virus (TSWV), belonging to the genus Tospovirus of the family
      Bunyaviridae, causes significant economic damage to several vegetables and
      ornamental plants worldwide. Similar to those of all other negative-strand RNA
      viruses, the nucleocapsid (N) protein plays very important roles in its viral
      life cycle. N proteins protect genomic RNAs by encapsidation and form a viral
      ribonucleoprotein complex (vRNP) with some RNA-dependent RNA polymerases. Here we
      show the crystal structure of the N protein from TSWV. Protomers of TSWV N
      proteins consist of three parts: the N arm, C arm, and core domain. Unlike N
      proteins of other negative-strand RNA viruses, the TSWV N protein forms an
      asymmetric trimeric ring. To form the trimeric ring, the N and C arms of the N
      protein interact with the core domains of two adjacent N proteins. By solving the
      crystal structures of the TSWV N protein with nucleic acids, we showed that an
      inner cleft of the asymmetric trimeric ring is an RNA-binding site. These
      characteristics are similar to those of N proteins of other viruses of the family
      Bunyaviridae Based on these observations, we discuss possibilities of a TSWV
      encapsidation model.IMPORTANCE Tospoviruses cause significant crop losses
      throughout the world. Particularly, TSWV has an extremely wide host range (>1,000
      plant species, including dicots and monocots), and worldwide losses are estimated
      to be in excess of $1 billion annually. Despite such importance, no proteins of
      tospoviruses have been elucidated so far. Among TSWV-encoded proteins, the N
      protein is required for assembling the viral genomic RNA into the viral
      ribonucleoprotein (vRNP), which is involved in various steps of the life cycle of
      these viruses, such as RNA replication, virus particle formation, and cell-to
      cell movement. This study revealed the structure of the N protein, with or
      without nucleic acids, of TSWV as the first virus of the genus Tospovirus, so it
      completed our view of the N proteins of the family Bunyaviridae.

PMID- 28768869
TI  - Protective Efficacy of Broadly Neutralizing Antibodies with Incomplete
      Neutralization Activity against Simian-Human Immunodeficiency Virus in Rhesus
      Monkeys.
AB  - HIV broadly neutralizing antibodies (bnAbs) have been shown to occasionally
      display unusual virus neutralization profiles with nonsigmoidal slopes and
      plateaus at <100% neutralization against a variety of viruses. The significance
      of incomplete neutralization for the ability of bnAbs to mediate protective
      effects in vivo, however, is undetermined. In the current study, we selected two
      bnAbs, PGT121 and 3BNC117, as they incompletely neutralize the clade C simian
      human immunodeficiency virus (SHIV) stock (SHIV-327c) at 85% and 70%,
      respectively, and performed a protection study in rhesus macaques. The animals
      were intravenously (i.v.) administered PGT121 or 3BNC117 at 10 and 2 mg/kg of
      body weight before being rectally challenged with a single high dose of SHIV
      327c. PGT121 protected 6 out of 7 monkeys, while 6 out of 7 3BNC117-pretreated
      animals became infected, although with significantly delayed plasma viremia
      compared to the control animals. These data suggest that complete neutralization
      is not imperative for bnAbs to prevent infection but that with increasing levels
      of incomplete neutralization the sterilizing activity diminishes.IMPORTANCE
      Multiple antibodies have been identified that potently neutralize a broad range
      of circulating HIV strains. However, not every virus-antibody combination results
      in complete neutralization of the input virus, suggesting that a fraction of
      virus particles are resistant to antibody neutralization despite high antibody
      concentrations. This observation of "incomplete neutralization" is associated
      with nonsigmoidal neutralization curves plateauing below 100% neutralization, but
      the significance of the phenomenon for the ability of neutralizing antibodies to
      mediate protective effects in vivo is undetermined. In this study, we show that
      the broadly neutralizing antibody PGT121, which neutralized only up to 85% of the
      SHIV-327c challenge stock in vitro, protected 6 out of 7 rhesus macaques against
      infection while the antibody 3BNC117, which neutralized up to 70% of SHIV-327c in
      vitro, did not prevent, though it significantly delayed, establishment of
      infection, suggesting that with increasing levels of incomplete neutralization
      the ability of a bnAb to mediate sterilizing protection diminishes.

PMID- 28768871
TI  - Isolation and Characterization of Metallosphaera turreted icosahedral virus
      (MTIV), a founding member of a new family of archaeal viruses.
AB  - Our understanding of archaeal virus diversity and structure is just beginning to
      emerge. Here we describe a new archaeal virus, tentatively named Metallosphaera
      turreted icosahedral virus (MTIV), that was isolated from an acidic hot spring in
      Yellowstone National Park, USA. Two strains of the virus were identified and
      found to replicate in an archaeal host species closely related to Metallosphaera
      yellowstonensis Each strain encodes for a 9.8-9.9 kb, linear dsDNA genome with
      large inverted terminal repeats. Each genome encodes for 21 ORFs. Between the
      strains the ORFs display high homology, but they are quite distinct from other
      known viral genes. The 70-nm diameter virion is built upon on a T=28 icosahedral
      lattice. Both single particle cryo-electron microscopy and cryo-tomography
      reconstructions reveal an unusual structure that has 42 turret-like projections:
      12 from each of the 5-fold axes and 30 hexameric units positioned on icosahedral
      2-fold axes. Both the virion structural properties and genome content support
      MTIV as the founding member of a new family of archaeal viruses.Importance: Many
      archaeal viruses are quite different than viruses infecting bacteria and
      eukaryotes. Initial characterization of MTIV reveals a virus distinct from other
      known bacterial, eukaryotic, and archaeal viruses; this finding suggests that
      viruses infecting Archaea are still an understudied group of viruses. As the
      first known virus infecting the Metallosphaera, MTIV provides a new system for
      exploring archaeal virology by examining host-virus interactions and the unique
      features of MTIV structure-function relationships. These studies will likely
      expand our understanding of virus ecology and evolution.

PMID- 28768870
TI  - Replication of JC Virus DNA in the G144 Oligodendrocyte Cell Line Is Dependent
      Upon Akt.
AB  - Progressive multifocal leukoencephalopathy (PML) is an often-fatal demyelinating
      disease of the central nervous system. PML results when oligodendrocytes within
      immunocompromised individuals are infected with the human JC virus (JCV). We have
      identified an oligodendrocyte precursor cell line, termed G144, that supports
      robust levels of JCV DNA replication, a central part of the JCV life cycle. In
      addition, we have determined that JC virus readily infects G144 cells.
      Furthermore, we have determined that JCV DNA replication in G144 cells is
      stimulated by myristoylated (i.e., constitutively active) Akt and reduced by the
      Akt-specific inhibitor MK2206. Thus, this oligodendrocyte-based model system will
      be useful for a number of purposes, such as studies of JCV infection,
      establishing key pathways needed for the regulation of JCV DNA replication, and
      identifying inhibitors of this process.IMPORTANCE The disease progressive
      multifocal leukoencephalopathy (PML) is caused by the infection of particular
      brain cells, termed oligodendrocytes, by the JC virus. Studies of PML, however,
      have been hampered by the lack of an immortalized human cell line derived from
      oligodendrocytes. Here, we report that the G144 oligodendrocyte cell line
      supports both infection by JC virus and robust levels of JCV DNA replication.
      Moreover, we have established that the Akt pathway regulates JCV DNA replication
      and that JCV DNA replication can be inhibited by MK2206, a compound that is
      specific for Akt. These and related findings suggest that we have established a
      powerful oligodendrocyte-based model system for studies of JCV-dependent PML.

PMID- 28768873
TI  - Human Herpesvirus 8 Infects and Replicates in Langerhans Cells and Interstitial
      Dermal Dendritic Cells and Impairs Their Function.
AB  - The predominant types of dendritic cells (DC) in the skin and mucosa are
      Langerhans cells (LC) and interstitial dermal DC (iDDC). LC and iDDC process
      cutaneous antigens and migrate out of the skin and mucosa to the draining lymph
      nodes to present antigens to T and B cells. Because of the strategic location of
      LC and iDDC and the ability of these cells to capture and process pathogens, we
      hypothesized that they could be infected with human herpesvirus 8 (HHV-8)
      (Kaposi's sarcoma [KS]-associated herpesvirus) and have an important role in the
      development of KS. We have previously shown that HHV-8 enters monocyte-derived
      dendritic cells (MDDC) through DC-SIGN, resulting in nonproductive infection.
      Here we show that LC and iDDC generated from pluripotent cord blood CD34+ cell
      precursors support productive infection with HHV-8. Anti-DC-SIGN monoclonal
      antibody (MAb) inhibited HHV-8 infection of iDDC, as shown by low expression
      levels of viral proteins and DNA. In contrast, blocking of both langerin and the
      receptor protein tyrosine kinase ephrin A2 was required to inhibit HHV-8
      infection of LC. Infection with HHV-8 did not alter the cell surface expression
      of langerin on LC but downregulated the expression of DC-SIGN on iDDC, as we
      previously reported for MDDC. HHV-8-infected LC and iDDC had a reduced ability to
      stimulate allogeneic CD4+ T cells in the mixed-lymphocyte reaction. These results
      indicate that HHV-8 can target both LC and iDDC for productive infection via
      different receptors and alter their function, supporting their potential role in
      HHV-8 pathogenesis and KS.IMPORTANCE Here we show that HHV-8, a DNA tumor virus
      that causes Kaposi's sarcoma, infects three types of dendritic cells: monocyte
      derived dendritic cells, Langerhans cells, and interstitial dermal dendritic
      cells. We show that different receptors are used by this virus to infect these
      cells. DC-SIGN is a major receptor for infection of both monocyte-derived
      dendritic cells and interstitial dermal dendritic cells, yet the virus fully
      replicates only in the latter. HHV-8 uses langerin and the ephrin A2 receptor to
      infect Langerhans cells, which support full HHV-8 lytic replication. This
      infection of Langerhans cells and interstitial dermal dendritic cells results in
      an impaired ability to stimulate CD4+ helper T cell responses. Taken together,
      our data show that HHV-8 utilizes alternate receptors to differentially infect
      and replicate in these tissue-resident DC and support the hypothesis that these
      cells play an important role in HHV-8 infection and pathogenesis.

PMID- 28768872
TI  - High-Risk Alphapapillomavirus Oncogenes Impair the Homologous Recombination
      Pathway.
AB  - Persistent high-risk genus human Alphapapillomavirus (HPV) infections cause
      nearly every cervical carcinoma and a subset of tumors in the oropharyngeal
      tract. During the decades required for HPV-associated tumorigenesis, the cellular
      genome becomes significantly destabilized. Our analysis of cervical tumors from
      four separate data sets found a significant upregulation of the homologous
      recombination (HR) pathway genes. The increased abundance of HR proteins can be
      replicated in primary cells by expression of the two HPV oncogenes (E6 and E7)
      required for HPV-associated transformation. HPV E6 and E7 also enhanced the
      ability of HR proteins to form repair foci, and yet both E6 and E7 reduce the
      ability of the HR pathway to complete double-strand break (DSB) repair by about
      50%. The HPV oncogenes hinder HR by allowing the process to begin at points in
      the cell cycle when the lack of a sister chromatid to serve as a homologous
      template prevents completion of the repair. Further, HPV E6 attenuates repair by
      causing RAD51 to be mislocalized away from both transient and persistent DSBs,
      whereas HPV E7 is only capable of impairing RAD51 localization to transient
      lesions. Finally, we show that the inability to robustly repair DSBs causes some
      of these lesions to be more persistent, a phenotype that correlates with
      increased integration of episomal DNA. Together, these data support our
      hypothesis that HPV oncogenes contribute to the genomic instability observed in
      HPV-associated malignancies by attenuating the repair of damaged DNA.IMPORTANCE
      This study expands the understanding of HPV biology, establishing a direct role
      for both HPV E6 and E7 in the destabilization of the host genome by blocking the
      homologous repair of DSBs. To our knowledge, this is the first time that both
      viral oncogenes were shown to disrupt this DSB repair pathway. We show that HPV
      E6 and E7 allow HR to initiate at an inappropriate part of the cell cycle. The
      mislocalization of RAD51 away from DSBs in cells expressing HPV E6 and E7 hinders
      HR through a distinct mechanism. These observations have broad implications. The
      impairment of HR by HPV oncogenes may be targeted for treatment of HPV+
      malignancies. Further, this attenuation of repair suggests HPV oncogenes may
      contribute to tumorigenesis by promoting the integration of the HPV genome, a
      common feature of HPV-transformed cells. Our data support this idea since HPV E6
      stimulates the integration of episomes.

PMID- 28768874
TI  - PGC1alpha Transcriptional Adaptor Function Governs Hepatitis B Virus Replication
      by Controlling HBcAg/p21 Protein-Mediated Capsid Formation.
AB  - In the human hepatoma cell line Huh7, the coexpression of the coactivators
      peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha),
      cyclic AMP-responsive element binding protein binding protein (CBP), steroid
      receptor coactivator 1 (SRC1), and protein arginine methyltransferase 1 (PRMT1)
      only modestly increase hepatitis B virus (HBV) biosynthesis. However, by
      utilizing the human embryonic kidney cell line HEK293T, it was possible to
      demonstrate that PGC1alpha alone can support viral biosynthesis independently of
      the expression of additional coactivators or transcription factors. In contrast,
      additional coactivators failed to support robust HBV replication in the absence
      of PGC1alpha. These observations indicate that PGC1alpha represents a novel
      adaptor molecule capable of recruiting the necessary transcriptional machinery to
      the HBV nucleocapsid promoter to modestly enhance viral pregenomic 3.5-kb RNA
      synthesis. Although this change in transcription is associated with a similar
      modest change in hepatitis B virus core antigen polypeptide (HBcAg/p21)
      synthesis, it mediates a dramatic increase in viral capsid production and robust
      viral replication. Therefore, it is apparent that the synthesis of cytoplasmic
      HBcAg/p21 above a critical threshold level is required for the efficient assembly
      of HBV replication-competent viral capsids.IMPORTANCE Hepatitis B virus (HBV) is
      a major human pathogen, and novel targets for the development of additional
      therapeutic agents are urgently needed. Here we demonstrate that the coactivator
      peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha)
      serves as a unique adaptor molecule for the recruitment of additional coactivator
      proteins, which can finely regulate HBV transcription. The consequence of this
      precise regulation of viral RNA levels by PGC1alpha is a subtle increase in
      cytoplasmic HBcAg/p21 polypeptide translation, which shifts the equilibrium from
      dimer formation dramatically in favor of viral capsid assembly. These findings
      suggest that both PGC1alpha and capsid assembly may represent attractive targets
      for the development of antiviral agents against chronic HBV infection.

PMID- 28768875
TI  - Relevance of Assembly-Activating Protein for Adeno-associated Virus Vector
      Production and Capsid Protein Stability in Mammalian and Insect Cells.
AB  - The discovery that adeno-associated virus 2 (AAV2) encodes an eighth protein,
      called assembly-activating protein (AAP), transformed our understanding of wild
      type AAV biology. Concurrently, it raised questions about the role of AAP during
      production of recombinant vectors based on natural or molecularly engineered AAV
      capsids. Here, we show that AAP is indeed essential for generation of functional
      recombinant AAV2 vectors in both mammalian and insect cell-based vector
      production systems. Surprisingly, we observed that AAV2 capsid proteins VP1 to -3
      are unstable in the absence of AAP2, likely due to rapid proteasomal degradation.
      Inhibition of the proteasome led to an increase of intracellular VP1 to -3 but
      neither triggered assembly of functional capsids nor promoted nuclear
      localization of the capsid proteins. Together, this underscores the crucial and
      unique role of AAP in the AAV life cycle, where it rapidly chaperones capsid
      assembly, thus preventing degradation of free capsid proteins. An expanded
      analysis comprising nine alternative AAV serotypes (1, 3 to 9, and rh10) showed
      that vector production always depends on the presence of AAP, with the exceptions
      of AAV4 and AAV5, which exhibited AAP-independent, albeit low-level, particle
      assembly. Interestingly, AAPs from all 10 serotypes could cross-complement AAP
      depleted helper plasmids during vector production, despite there being distinct
      intracellular AAP localization patterns. These were most pronounced for AAP4 and
      AAP5, congruent with their inability to rescue an AAV2/AAP2 knockout. We conclude
      that AAP is key for assembly of genuine capsids from at least 10 different AAV
      serotypes, which has implications for vectors derived from wild-type or synthetic
      AAV capsids.IMPORTANCE Assembly of adeno-associated virus 2 (AAV2) is regulated
      by the assembly-activating protein (AAP), whose open reading frame overlaps with
      that of the viral capsid proteins. As the majority of evidence was obtained using
      virus-like particles composed solely of the major capsid protein VP3, AAP's role
      in and relevance for assembly of genuine AAV capsids have remained largely
      unclear. Thus, we established a trans-complementation assay permitting assessment
      of AAP functionality during production of recombinant vectors based on complete
      AAV capsids and derived from any serotype. We find that AAP is indeed a critical
      factor not only for AAV2, but also for generation of vectors derived from nine
      other AAV serotypes. Moreover, we identify a new role of AAP in maintaining
      capsid protein stability in mammalian and insect cells. Thereby, our study
      expands our current understanding of AAV/AAP biology, and it concomitantly
      provides insights into the importance of AAP for AAV vector production.

PMID- 28768876
TI  - Monoclonal Antibodies against Zika Virus: Therapeutics and Their Implications for
      Vaccine Design.
AB  - Zika virus (ZIKV) has caused global concern due to its association with
      neurological complications in newborns and adults. Although no vaccines or
      antivirals against ZIKV infection have been approved to date, hundreds of
      monoclonal antibodies (MAbs) have been developed in a short period. Here, we
      first present a complete picture of the ZIKV MAbs and then focus on the
      neutralizing mechanisms and immune hot spots uncovered through structural
      studies, which provide insight for therapeutics and vaccine design.

PMID- 28768877
TI  - Immunodominance of Adenovirus-Derived CD8+ T Cell Epitopes Interferes with the
      Induction of Transgene-Specific Immunity in Adenovirus-Based Immunization.
AB  - Adenovirus (Ad)-based immunization is a popular approach in vaccine development,
      and Ad-based vectors are renowned for their potential to induce strong CD8+ T
      cell responses to the encoded transgene. Surprisingly, we previously found in the
      mouse Friend retrovirus (FV) model that Ad-based immunization did not induce CD8+
      T cell responses to the FV Leader-Gag-derived immunodominant epitope GagL85-93 We
      show now that induction of GagL85-93-specific CD8+ T cells was highly effective
      when leader-Gag was delivered by plasmid DNA immunization, implying a role for Ad
      derived epitopes in mediating unresponsiveness. By immunizing with DNA constructs
      encoding strings of GagL85-93 and the two Ad-derived epitopes DNA-binding
      protein418-426 (DBP418-426) and hexon486-494, we confirmed that Ad epitopes
      prevent induction of GagL85-93-specific CD8+ T cells. Interestingly, while DBP418
      426 did not interfere with GagL85-93-specific CD8+ T cell induction, the H-2Dd
      restricted hexon486-494 suppressed the CD8+ T cell response to the H-2Db
      restricted GagL85-93 strongly in H-2b/d mice but not in H-2b/b mice. This finding
      indicates that competition occurs at the level of responding CD8+ T cells, and we
      could indeed demonstrate that coimmunization with an interleukin 2 (IL-2)
      encoding plasmid restored GagL85-93-specific CD8+ T cell responses to epitope
      strings in the presence of hexon486-494 IL-2 codelivery did not restore GagL85-93
      responsiveness in Ad-based immunization, however, likely due to the presence of
      further epitopes in the Ad vector. Our findings show that seemingly
      immunodominant transgene epitopes can be dominated by Ad-derived epitopes. These
      findings underline the importance of thorough characterization of vaccine
      vectors, and modifications of vectors or immunogens may be required to prevent
      impaired transgene-specific immune responses.IMPORTANCE Ad-based vectors are
      widely used in experimental preclinical and clinical immunization studies against
      numerous infectious agents, such as human immunodeficiency virus, Ebola virus,
      Plasmodium falciparum, or Mycobacterium tuberculosis Preexisting immunity to Ad
      based vectors is widely recognized as a hindrance to the widespread use of Ad
      based vectors for immunizations in humans; however, our data show that an immune
      response to Ad-derived T cell epitopes can also result in loss or impairment of
      transgene-specific immune responses in prenaive vaccinees due to immune
      competition. Our results highlight that seemingly immunodominant epitopes may be
      affected by dominance of vector-derived epitopes, and modifications of the vector
      design or the immunogens employed in immunization may lead to more effective
      vaccines.

PMID- 28768878
TI  - Controllable biomimetic birdsong.
AB  - Birdsong is the product of the controlled generation of sound embodied in a
      neuromotor system. From a biophysical perspective, a natural question is that of
      the difficulty of producing birdsong. To address this, we built a biomimetic
      syrinx consisting of a stretched simple rubber tube through which air is blown,
      subject to localized mechanical squeezing with a linear actuator. A large static
      tension on the tube and small dynamic variations in the localized squeezing allow
      us to control transitions between three states: a quiescent state, a periodic
      state and a solitary wave state. The static load brings the system close to
      threshold for spontaneous oscillations, while small dynamic loads allow for rapid
      transitions between the states. We use this to mimic a variety of birdsongs via
      the slow-fast modulated nonlinear dynamics of the physical substrate, the syrinx,
      regulated by a simple controller. Finally, a minimal mathematical model of the
      system inspired by our observations allows us to address the problem of song
      mimicry in an excitable oscillator for tonal songs.

PMID- 28768879
TI  - How to deal with parameters for whole-cell modelling.
AB  - Dynamical systems describing whole cells are on the verge of becoming a reality.
      But as models of reality, they are only useful if we have realistic parameters
      for the molecular reaction rates and cell physiological processes. There is
      currently no suitable framework to reliably estimate hundreds, let alone
      thousands, of reaction rate parameters. Here, we map out the relative weaknesses
      and promises of different approaches aimed at redressing this issue. While
      suitable procedures for estimation or inference of the whole (vast) set of
      parameters will, in all likelihood, remain elusive, some hope can be drawn from
      the fact that much of the cellular behaviour may be explained in terms of smaller
      sets of parameters. Identifying such parameter sets and assessing their behaviour
      is now becoming possible even for very large systems of equations, and we expect
      such methods to become central tools in the development and analysis of whole
      cell models.

PMID- 28768880
TI  - Hyaluronan supplementation as a mechanical regulator of cartilage tissue
      development under joint-kinematic-mimicking loading.
AB  - Articular cartilage plays an essential role in joint lubrication and impact
      absorption. Through this, the mechanical signals are coupled to the tissue's
      physiological response. Healthy synovial fluid has been shown to reduce and
      homogenize the shear stress acting on the cartilage surfaces due to its unique
      shear-thinning viscosity. As cartilage tissues are sensitive to mechanical
      changes in articulation, it was hypothesized that replacing the traditional
      culture medium with a healthy non-Newtonian lubricant could enhance tissue
      development in a cartilage engineering model, where joint-kinematic-mimicking
      mechanical loading is applied. Different amounts of hyaluronic acid were added to
      the culture medium to replicate the viscosities of synovial fluid at different
      health states. Hyaluronic acid supplementation, especially at a physiologically
      healthy concentration (2.0 mg ml-1), promoted a better preservation of
      chondrocyte phenotype. The ratio of collagen II to collagen I mRNA was 4.5 times
      that of the control group, implying better tissue development (however, with no
      significant difference of measured collagen II content), with a good retention of
      collagen II and proteoglycan in the mechanically active region. Simulating
      synovial fluid properties by hyaluronic acid supplementation created a favourable
      mechanical environment for mechanically loaded constructs. These findings may
      help in understanding the influence of joint articulation on tissue homeostasis,
      and moreover, improve methods for functional cartilage tissue engineering.

PMID- 28768881
TI  - Hydrodynamic advantages of swimming by salp chains.
AB  - Salps are marine invertebrates comprising multiple jet-propelled swimming units
      during a colonial life-cycle stage. Using theory, we show that asynchronous
      swimming with multiple pulsed jets yields substantial hydrodynamic benefit due to
      the production of steady swimming velocities, which limit drag. Laboratory
      comparisons of swimming kinematics of aggregate salps (Salpa fusiformis and
      Weelia cylindrica) using high-speed video supported that asynchronous swimming by
      aggregates results in a smoother velocity profile and showed that this smoother
      velocity profile is the result of uncoordinated, asynchronous swimming by
      individual zooids. In situ flow visualizations of W. cylindrica swimming wakes
      revealed that another consequence of asynchronous swimming is that fluid
      interactions between jet wakes are minimized. Although the advantages of multi
      jet propulsion have been mentioned elsewhere, this is the first time that the
      theory has been quantified and the role of asynchronous swimming verified using
      experimental data from the laboratory and the field.

PMID- 28768882
TI  - Connexin membrane materials as potent inhibitors of breast cancer cell migration.
AB  - Gap junction (GJ) channels facilitate cell-cell communication through the
      exchange of chemical and mechanical signals, ensuring proper tissue development
      and homeostasis. The complex, disease stage-dependent role of connexins in breast
      cancer progression has been extensively studied over the past two decades. In the
      early stages of breast cancer, substantial evidence supports the role of GJ
      channels, formed by connexins at the interfaces between neighbouring cells, as
      suppressors of cell migration and proliferation. These findings suggest that
      materials that reintroduce connexins into the tumour cell environment have the
      potential to inhibit cell migration. Here, we report that exposure of highly
      metastatic MDA-MB-231 breast tumour cells to connexin-rich biovesicle materials
      potently suppresses cell migration. Specifically, these biovesicles, which can
      form GJ interfaces with cells, were extracted from the plasma membrane of donor
      cells engineered to express a high concentration of functional connexin 43
      channels. These connexin-rich membrane materials dramatically reduced cell
      migration in both a transwell migration assay and a scratch closure assay.
      Collectively, these results suggest that using membrane materials to reintroduce
      connexins into the tumour cell environment provides a novel approach for
      combating cell migration and invasion.

PMID- 28768883
TI  - Structural coloured feathers of mallards act by simple multilayer photonics.
AB  - The blue colours of the speculum of the mallard (Anas platyrhynchos), both male
      and female, and the green head feathers of the male arise from light interacting
      with stacks of melanosomes residing in the feather barbules. Here, we show that
      the iridescent colours can be quantitatively explained with an optical multilayer
      model by using a position-dependent effective refractive index, which results
      from the varying ratio of melanin and keratin. Reflectance spectra obtained by
      multilayer modelling and three-dimensional finite-difference time-domain
      calculations were virtually identical. The spectral properties of the barbules'
      photonic structures are sensitive to variations in the multilayer period and the
      cortex thickness, but they are surprisingly robust to variations in the spatial
      parameters of the barbules' melanosome stacks. The blue and green reflectance
      spectra of the structural-coloured feathers correspond with the sensitivity
      spectra of the short- and middle-wavelength-sensitive photoreceptors, indicating
      their biological significance for intraspecific signalling.

PMID- 28768884
TI  - Climate change and body size shift in Mediterranean bivalve assemblages:
      unexpected role of biological invasions.
AB  - Body size is a synthetic functional trait determining many key ecosystem
      properties. Reduction in average body size has been suggested as one of the
      universal responses to global warming in aquatic ecosystems. Climate change,
      however, coincides with human-enhanced dispersal of alien species and can
      facilitate their establishment. We address effects of species introductions on
      the size structure of recipient communities using data on Red Sea bivalves
      entering the Mediterranean Sea through the Suez Canal. We show that the invasion
      leads to increase in median body size of the Mediterranean assemblage. Alien
      species are significantly larger than native Mediterranean bivalves, even though
      they represent a random subset of the Red Sea species with respect to body size.
      The observed patterns result primarily from the differences in the taxonomic
      composition and body-size distributions of the source and recipient species
      pools. In contrast to the expectations based on the general temperature-size
      relationships in marine ectotherms, continued warming of the Mediterranean Sea
      indirectly leads to an increase in the proportion of large-bodied species in
      bivalve assemblages by accelerating the entry and spread of tropical aliens.
      These results underscore complex interactions between changing climate and
      species invasions in driving functional shifts in marine ecosystems.

PMID- 28768885
TI  - Satellite telemetry reveals higher fishing mortality rates than previously
      estimated, suggesting overfishing of an apex marine predator.
AB  - Overfishing is a primary cause of population declines for many shark species of
      conservation concern. However, means of obtaining information on fishery
      interactions and mortality, necessary for the development of successful
      conservation strategies, are often fisheries-dependent and of questionable
      quality for many species of commercially exploited pelagic sharks. We used
      satellite telemetry as a fisheries-independent tool to document fisheries
      interactions, and quantify fishing mortality of the highly migratory shortfin
      mako shark (Isurus oxyrinchus) in the western North Atlantic Ocean. Forty
      satellite-tagged shortfin mako sharks tracked over 3 years entered the Exclusive
      Economic Zones of 19 countries and were harvested in fisheries of five countries,
      with 30% of tagged sharks harvested. Our tagging-derived estimates of
      instantaneous fishing mortality rates (F = 0.19-0.56) were 10-fold higher than
      previous estimates from fisheries-dependent data (approx. 0.015-0.024),
      suggesting data used in stock assessments may considerably underestimate fishing
      mortality. Additionally, our estimates of F were greater than those associated
      with maximum sustainable yield, suggesting a state of overfishing. This
      information has direct application to evaluations of stock status and for
      effective management of populations, and thus satellite tagging studies have
      potential to provide more accurate estimates of fishing mortality and survival
      than traditional fisheries-dependent methodology.

PMID- 28768886
TI  - Oceanic protists with different forms of acquired phototrophy display contrasting
      biogeographies and abundance.
AB  - This first comprehensive analysis of the global biogeography of marine protistan
      plankton with acquired phototrophy shows these mixotrophic organisms to be
      ubiquitous and abundant; however, their biogeography differs markedly between
      different functional groups. These mixotrophs, lacking a constitutive capacity
      for photosynthesis (i.e. non-constitutive mixotrophs, NCMs), acquire their
      phototrophic potential through either integration of prey-plastids or through
      endosymbiotic associations with photosynthetic microbes. Analysis of field data
      reveals that 40-60% of plankton traditionally labelled as (non-phototrophic)
      microzooplankton are actually NCMs, employing acquired phototrophy in addition to
      phagotrophy. Specialist NCMs acquire chloroplasts or endosymbionts from specific
      prey, while generalist NCMs obtain chloroplasts from a variety of prey. These
      contrasting functional types of NCMs exhibit distinct seasonal and spatial global
      distribution patterns. Mixotrophs reliant on 'stolen' chloroplasts, controlled by
      prey diversity and abundance, dominate in high-biomass areas. Mixotrophs
      harbouring intact symbionts are present in all waters and dominate particularly
      in oligotrophic open ocean systems. The contrasting temporal and spatial patterns
      of distribution of different mixotroph functional types across the oceanic
      provinces, as revealed in this study, challenges traditional interpretations of
      marine food web structures. Mixotrophs with acquired phototrophy (NCMs) warrant
      greater recognition in marine research.

PMID- 28768887
TI  - Phosphotyrosine signalling and the origin of animal multicellularity.
AB  - The evolution of multicellular animals (i.e. metazoans) from a unicellular
      ancestor is one of the most important yet least understood evolutionary
      transitions. Historically, given its indispensable functions in intercellular
      communication and exclusive presence in metazoans, phosphotyrosine (pTyr)
      signalling was considered a metazoan-specific evolutionary innovation that might
      have contributed to the origin of metazoan multicellularity. However, recent
      studies have led to a new understanding of pTyr signalling evolution and its role
      in the metazoan origin. Sequence analyses have unravelled a much earlier
      emergence of pTyr signalling in eukaryotic evolution. Even so, several distinct
      properties of holozoan pTyr signalling may have paved the way for a hypothesized
      functional transition of pTyr signalling at the multicellular origin, from
      environmental sensing to intercellular communication, and for it to evolve as a
      powerful intercellular signalling system for multicellularity. Biochemical
      analyses of premetazoan pTyr signalling components have further revealed the
      premetazoan origin of many key features of metazoan pTyr signalling, and the
      metazoan establishment of others, including the Csk-mediated negative regulation
      of the activity of Src, a conserved tyrosine kinase in the Holozoa. Finally,
      potential future directions are discussed, with a stress on the biological
      functions of premetazoan pTyr signalling via newly developed gene manipulation
      tools in non-animal holozoans.

PMID- 28768888
TI  - Dynamical state transitions into addictive behaviour and their early-warning
      signals.
AB  - The theory of critical transitions in complex systems (ecosystems, climate,
      etc.), and especially its ability to predict abrupt changes by early-warning
      signals based on analysis of fluctuations close to tipping points, is seen as a
      promising avenue to study disease dynamics. However, the biomedical field still
      lacks a clear demonstration of this concept. Here, we used a well-established
      animal model in which initial alcohol exposure followed by deprivation and
      subsequent reintroduction of alcohol induces excessive alcohol drinking as an
      example of disease onset. Intensive longitudinal data (ILD) of rat drinking
      behaviour and locomotor activity were acquired by a fully automated drinkometer
      device over 14 weeks. Dynamical characteristics of ILD were extracted using a
      multi-scale computational approach. Our analysis shows a transition into
      addictive behaviour preceded by early-warning signals such as instability of
      drinking patterns and locomotor circadian rhythms, and a resultant increase in
      low frequency, ultradian rhythms during the first week of deprivation. We find
      evidence that during prolonged deprivation, a critical transition takes place
      pushing the system to excessive alcohol consumption. This study provides an
      adaptable framework for processing ILD from clinical studies and for examining
      disease dynamics and early-warning signals in the biomedical field.

PMID- 28768889
TI  - Decoupled diversification dynamics of feeding morphology following a major
      functional innovation in marine butterflyfishes.
AB  - The diversity of fishes on coral reefs is influenced by the evolution of feeding
      innovations. For instance, the evolution of an intramandibular jaw joint has
      aided shifts to corallivory in Chaetodon butterflyfishes following their Miocene
      colonization of coral reefs. Today, over half of all Chaetodon species consume
      coral, easily the largest concentration of corallivores in any reef fish family.
      In contrast with Chaetodon, other chaetodontids, including the long-jawed
      bannerfishes, remain less intimately associated with coral and mainly consume
      other invertebrate prey. Here, we test (i) if intramandibular joint (IMJ)
      evolution in Chaetodon has accelerated feeding morphological diversification, and
      (ii) if cranial and post-cranial traits were affected similarly. We measured 19
      cranial functional morphological traits, gut length and body elongation for 33
      Indo-Pacific species. Comparisons of Brownian motion rate parameters revealed
      that cranial diversification was about four times slower in Chaetodon
      butterflyfishes with the IMJ than in other chaetodontids. However, the rate of
      gut length evolution was significantly faster in Chaetodon, with no group
      differences for body elongation. The contrasting patterns of cranial and post
      cranial morphological evolution stress the importance of comprehensive datasets
      in ecomorphology. The IMJ appears to enhance coral feeding ability in Chaetodon
      and represents a design breakthrough that facilitates this trophic strategy.
      Meanwhile, variation in gut anatomy probably reflects diversity in how coral
      tissues are procured and assimilated. Bannerfishes, by contrast, retain a
      relatively unspecialized gut for processing invertebrate prey, but have evolved
      some of the most extreme cranial mechanical innovations among bony fishes for
      procuring elusive prey.

PMID- 28768890
TI  - Is meiosis a fundamental cause of inviability among sexual and asexual plants and
      animals?
AB  - Differences in viability between asexually and sexually generated offspring
      strongly influence the selective advantage and therefore the prevalence of sexual
      reproduction (sex). However, no general principle predicts when sexual offspring
      will be more viable than asexual offspring. We hypothesize that when any kind of
      reproduction is based on a more complex cellular process, it will encompass more
      potential failure points, and therefore lower offspring viability. Asexual
      reproduction (asex) can be simpler than sex, when offspring are generated using
      only mitosis. However, when asex includes meiosis and meiotic restitution, gamete
      production is more complex than in sex. We test our hypothesis by comparing the
      viability of asexual and closely related sexual offspring across a wide range of
      plants and animals, and demonstrate that meiotic asex does result in lower
      viability than sex; without meiosis, asex is mechanistically simple and provides
      higher viability than sex. This phylogenetically robust pattern is supported in
      42 of 44 comparisons drawn from diverse plants and animals, and is not explained
      by the other variables included in our model. Other mechanisms may impact
      viability, such as effects of reproductive mode on heterozygosity and subsequent
      viability, but we propose the complexity of cellular processes of reproduction,
      particularly meiosis, as a fundamental cause of early developmental failure and
      mortality. Meiosis, the leading cause of inviability in humans, emerges as a
      likely explanation of offspring inviability among diverse eukaryotes.

PMID- 28768891
TI  - The evolution of dual meat and milk cattle husbandry in Linearbandkeramik
      societies.
AB  - Cattle dominate archaeozoological assemblages from the north-central Europe
      between the sixth and fifth millennium BC and are frequently considered as
      exclusively used for their meat. Dairy products may have played a greater role
      than previously believed. Selective pressure on the lactase persistence mutation
      has been modelled to have begun between 6000 and 4000 years ago in central
      Europe. The discovery of milk lipids in late sixth millennium ceramic sieves in
      Poland may reflect an isolated regional peculiarity for cheese making or may
      signify more generalized milk exploitation in north-central Europe during the
      Early Neolithic. To investigate these issues, we analysed the mortality profiles
      based on age-at-death analysis of cattle tooth eruption, wear and replacement
      from 19 archaeological sites of the Linearbandkeramik (LBK) culture (sixth to
      fifth millennium BC). The results indicate that cattle husbandry was similar
      across time and space in the LBK culture with a degree of specialization for meat
      exploitation in some areas. Statistical comparison with reference age-at-death
      profiles indicate that mixed husbandry (milk and meat) was practised, with mature
      animals being kept. The analysis provides a unique insight into LBK cattle
      husbandry and how it evolved in later cultures in central and western Europe. It
      also opens a new perspective on how and why the Neolithic way of life developed
      through continental Europe and how dairy products became a part of the human
      diet.

PMID- 28768892
TI  - Baby fish working out: an epigenetic source of adaptive variation in the cichlid
      jaw.
AB  - Understanding the developmental processes that underlie the production of
      adaptive variation (i.e. the 'arrival of the fittest') is a major goal of
      evolutionary biology. While most evo-devo studies focus on the genetic
      underpinnings of adaptive phenotypic variation, factors beyond changes in
      nucleotide sequence can also play a major role in shaping developmental outcomes.
      Here, we document a vigorous but enigmatic gaping behaviour during the early
      development of Lake Malawi cichlid larvae. The onset of the behaviour precedes
      the formation of bone, and we predicted that it might influence craniofacial
      shape by affecting the mechanical environment in which bone develops. Consistent
      with this, we found that both natural variation and experimental manipulation of
      this behaviour induced differential skeletal development that foreshadows
      adaptive variation in adult trophic morphology. In fact, the magnitude of
      difference in skeletal morphology induced by these simple shifts in behaviour was
      similar to those predicted to be caused by genetic factors. Finally, we
      demonstrate that this mechanical-load-induced shift in skeletal development is
      associated with differences in ptch1 expression, a gene previously implicated in
      mediating between-species differences in skeletal shape. Our results underscore
      the complexity of development, and the importance of epigenetic (sensu
      Waddington) mechanisms in determining adaptive phenotypic variation.

PMID- 28768893
TI  - Performance trade-offs and ageing in the 'world's greatest athletes'.
AB  - The mechanistic foundations of performance trade-offs are clear: because body
      size and shape constrains movement, and muscles vary in strength and fibre type,
      certain physical traits should act in opposition with others (e.g. sprint versus
      endurance). Yet performance trade-offs are rarely detected, and traits are often
      positively correlated. A potential resolution to this conundrum is that within
      individual performance trade-offs can be masked by among-individual variation in
      'quality'. Although there is a current debate on how to unambiguously define and
      account for quality, no previous studies have partitioned trait correlations at
      the within- and among-individual levels. Here, we evaluate performance trade-offs
      among and within 1369 elite athletes that performed in a total of 6418 combined
      events competitions (decathlon and heptathlon). Controlling for age, experience
      and wind conditions, we detected strong trade-offs between groups of functionally
      similar events (throwing versus jumping versus running) occurring at the among
      individual level. We further modelled individual (co)variation in age-related
      plasticity of performance and found previously unseen trade-offs in throwing
      versus running performance that manifest through ageing. Our results verify that
      human performance is limited by fundamental genetic, environmental and ageing
      constraints that preclude the simultaneous improvement of performance in multiple
      dimensions. Identifying these constraints is fundamental to understanding
      performance trade-offs and predicting the ageing of motor function.

PMID- 28768894
TI  - Phenotypic plasticity in reproductive effort: malaria parasites respond to
      resource availability.
AB  - The trade-off between survival and reproduction is fundamental in the life
      history of all sexually reproducing organisms. This includes malaria parasites,
      which rely on asexually replicating stages for within-host survival and on
      sexually reproducing stages (gametocytes) for between-host transmission. The
      proportion of asexual stages that form gametocytes (reproductive effort) varies
      during infections-i.e. is phenotypically plastic-in response to changes in a
      number of within-host factors, including anaemia. However, how the density and
      age structure of red blood cell (RBC) resources shape plasticity in reproductive
      effort and impacts upon parasite fitness is controversial. Here, we examine how
      and why the rodent malaria parasite Plasmodium chabaudi alters its reproductive
      effort in response to experimental perturbations of the density and age structure
      of RBCs. We show that all four of the genotypes studied increase reproductive
      effort when the proportion of RBCs that are immature is elevated during host
      anaemia, and that the responses of the genotypes differ. We propose that anaemia
      (counterintuitively) generates a resource-rich environment in which parasites can
      afford to allocate more energy to reproduction (i.e. transmission) and that
      anaemia also exposes genetic variation to selection. From an applied perspective,
      adaptive plasticity in parasite reproductive effort could explain the maintenance
      of genetic variation for virulence and why anaemia is often observed as a risk
      factor for transmission in human infections.

PMID- 28768895
TI  - p16(Ink4a) and senescence-associated beta-galactosidase can be induced in
      macrophages as part of a reversible response to physiological stimuli.
AB  - Constitutive p16Ink4a expression, along with senescence-associated beta
      galactosidase (SAbetaG), are commonly accepted biomarkers of senescent cells
      (SCs). Recent reports attributed improvement of the healthspan of aged mice
      following p16Ink4a-positive cell killing to the eradication of accumulated SCs.
      However, detection of p16Ink4a/SAbetaG-positive macrophages in the adipose tissue
      of old mice and in the peritoneal cavity of young animals following injection of
      alginate-encapsulated SCs has raised concerns about the exclusivity of these
      markers for SCs. Here we report that expression of p16Ink4a and SAbetaG in
      macrophages is acquired as part of a physiological response to immune stimuli
      rather than through senescence, consistent with reports that p16Ink4a plays a
      role in macrophage polarization and response. Unlike SCs, p16Ink4a/SAbetaG
      positive macrophages can be induced in p53-null mice. Macrophages, but not
      mesenchymal SCs, lose both markers in response to M1- [LPS, IFN-alpha, Poly(I:C)]
      and increase their expression in response to M2-inducing stimuli (IL-4, IL-13).
      Moreover, interferon-inducing agent Poly(I:C) dramatically reduced p16Ink4a
      expression in vivo in our alginate bead model and in the adipose tissue of aged
      mice. These observations suggest that the antiaging effects following eradication
      of p16Ink4a-positive cells may not be solely attributed to SCs but also to non
      senescent p16Ink4a/SAbetaG-positive macrophages.

PMID- 28768897
TI  - Strategies for the identification of disease-related patterns of volatile organic
      compounds: prediction of paratuberculosis in an animal model using random
      forests.
AB  - Modern statistical methods which were developed for pattern recognition are
      increasingly being used for data analysis in studies on emissions of volatile
      organic compounds (VOCs). With the detection of disease-related VOC profiles,
      novel non-invasive diagnostic tools could be developed for clinical applications.
      However, it is important to bear in mind that not all statistical methods are
      equally suitable for the investigation of VOC profiles. In particular, univariate
      methods are not able to discover VOC patterns as they consider each compound
      separately. The present study demonstrates this fact in practice. Using VOC
      samples from a controlled animal study on paratuberculosis, the random forest
      classification method was applied for pattern recognition and disease prediction.
      This strategy was compared with a prediction approach based on single compounds.
      Both methods were framed within a cross-validation procedure. A comparison of
      both strategies based on these VOC data reveals that random forests achieves
      higher sensitivities and specificities than predictions based on single
      compounds. Therefore, it will most likely be more fruitful to further investigate
      VOC patterns instead of single biomarkers for paratuberculosis. All methods used
      are thoroughly explained to aid the transfer to other data analyses.

PMID- 28768898
TI  - Morphological and functional consequences and quality of life following severe
      acute pancreatitis.
AB  - : In this study, we evaluated pancreatic morphology and function as well as
      nutritional status and quality of life among patients who experienced severe
      acute pancreatitis (SAP). MATERIALS AND METHODS: We enrolled 99 patients with SAP
      and 51 with mild acute pancreatitis (MAP). Computed tomography was performed one
      year following the disease. Endocrine function was evaluated by measuring
      hemoglobin A1c, insulin, and C peptide levels. Pancreatic exocrine insufficiency
      (PEI) was diagnosed by the concentration of fecal elastase-1. Nutritional status
      was assessed according to anthropometric parameters, albumin levels in blood
      serum, and the total number of lymphocytes. Quality of life was investigated
      using the Health Survey Questionnaire (SF-36). RESULTS: PEI was observed in 17.2%
      of patients after SAP vs. 7.8% of patients after MAP (p>0.05). Endocrine
      insufficiency was noted in 18.6% of patients after AP vs. 4.3% of patients after
      MAP (p<0.05). We observed changes in pancreatic morphology in 52.5% of patients
      after SAP and 9.8% of patients after MAP (p<0.0001). A medium risk of
      malnutrition was observed in 16.2% of patients after AP vs. 2% of patients after
      MAP (p=0.01). Patients with SAP described their mental health in more negative
      terms than patients with MAP (p<0.05). CONCLUSIONS: One year after SAP, patients
      exhibited changes in pancreatic morphology and carbohydrate metabolism disorders,
      and exocrine insufficiency occurred with a similar frequency. The majority of
      quality of life domains did not differ between patient groups. KEY WORDS: Acute
      pancreatitis, Pancreatic morphology, Pancreatic function.

PMID- 28768896
TI  - The effects of graded levels of calorie restriction: XI. Evaluation of the main
      hypotheses underpinning the life extension effects of CR using the hepatic
      transcriptome.
AB  - Calorie restriction (CR) may extend longevity by modulating the mechanisms
      involved in aging. Different hypotheses have been proposed for its main mode of
      action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded
      levels of CR (0% to 40% CR) for three months, and evaluated the responses
      relative to these various hypotheses. Of the four main signaling pathways implied
      to be linked to the impact of CR on lifespan (insulin/insulin like growth factor
      1 (IGF-1), nuclear factor-kappa beta (NF-KB), mechanistic target of rapamycin
      (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a
      manner consistent with increased lifespan. However, the expression levels of
      SIRT4 and SIRT7 were decreased with increasing levels of CR. Changes consistent
      with altered fuel utilization under CR may reduce reactive oxygen species
      production, which was paralleled by reduced protection. Downregulated major
      urinary protein (MUP) transcription suggested reduced reproductive investment.
      Graded CR had a positive effect on autophagy and xenobiotic metabolism, and was
      protective with respect to cancer signaling. CR had no significant effect on
      fibroblast growth factor-21 (FGF21) transcription but affected transcription in
      the hydrogen sulfide production pathway. Responses to CR were consistent with
      several different hypotheses, and the benefits of CR on lifespan likely reflect
      the combined impact on multiple aging related processes.

PMID- 28768899
TI  - Aberrant perichondrial BMP signaling mediates multiple osteochondromagenesis in
      mice.
AB  - Multiple hereditary exostoses (MHE) is characterized by the development of
      numerous benign bony tumors (osteochondromas). Although it has been well
      established that MHE is caused by mutations in EXT1 and EXT2, which encode
      glycosyltransferase essential for heparan sulfate (HS) biosynthesis, the cellular
      origin and molecular mechanisms of MHE remain elusive. Here, we show that in Ext1
      mutant mice, osteochondromas develop from mesenchymal stem cell-like progenitor
      cells residing in the perichondrium, and we show that enhanced BMP signaling in
      these cells is the primary signaling defect that leads to osteochondromagenesis.
      We demonstrate that progenitor cells in the perichondrium, including those in the
      groove of Ranvier, highly express HS and that Ext1 ablation targeted to the
      perichondrium results in the development of osteochondromas. Ext1-deficient
      perichondrial progenitor cells show enhanced BMP signaling and increased
      chondrogenic differentiation both in vitro and in vivo. Consistent with the
      functional role for enhanced BMP signaling in osteochondromagenesis,
      administration of the small molecule BMP inhibitor LDN-193189 suppresses
      osteochondroma formation in two MHE mouse models. Together, our results
      demonstrate a role for enhanced perichondrial BMP signaling in
      osteochondromagenesis in mice, and they suggest the possibility of
      pharmacological treatment of MHE with BMP inhibitors.

PMID- 28768901
TI  - Essential role for CCR6 in certain inflammatory diseases demonstrated using
      specific antagonist and knockin mice.
AB  - The chemokine receptor CCR6 marks subsets of T cells and innate lymphoid cells
      that produce IL-17 and IL-22, and as such may play a role in the recruitment of
      these cells to certain inflammatory sites. However, the precise role of CCR6 has
      been controversial, in part because no effective monoclonal antibody (mAb)
      inhibitors against this receptor exist for use in mouse models of inflammation.
      We circumvented this problem using transgenic mice expressing human CCR6 (hCCR6)
      under control of its native promoter (hCCR6-Tg/mCCR6-/-). We also developed a
      fully humanized mAb against hCCR6 with antagonistic activity. The expression
      pattern of hCCR6 in hCCR6-Tg/mCCR6-/- mice was consistent with the pattern
      observed in humans. In mouse models of experimental autoimmune encephalomyelitis
      (EAE) and psoriasis, treatment with anti-hCCR6 mAb was remarkably effective in
      both preventive and therapeutic regimens. For instance, in the imiquimod model of
      psoriasis, anti-CCR6 completely abolished all signs of inflammation. Moreover,
      anti-hCCR6 attenuated clinical symptoms of myelin oligodendrocyte glycoprotein
      induced (MOG-induced) EAE and reduced infiltration of inflammatory cells in the
      central nervous system. CCR6 plays a critical role in Th17 type inflammatory
      reactions, and CCR6 inhibition may offer an alternative approach for the
      treatment of these lesions.

PMID- 28768900
TI  - Plasminogen promotes cholesterol efflux by the ABCA1 pathway.
AB  - Using genetic and biochemical approaches, we investigated proteins that regulate
      macrophage cholesterol efflux capacity (CEC) and ABCA1-specific CEC (ABCA1 CEC),
      2 functional assays that predict cardiovascular disease (CVD). Macrophage CEC and
      the concentration of HDL particles were markedly reduced in mice deficient in
      apolipoprotein A-I (APOA1) or apolipoprotein E (APOE) but not apolipoprotein A-IV
      (APOA4). ABCA1 CEC was markedly reduced in APOA1-deficient mice but was barely
      affected in mice deficient in APOE or APOA4. High-resolution size-exclusion
      chromatography of plasma produced 2 major peaks of ABCA1 CEC activity. The early
      eluting peak, which coeluted with HDL, was markedly reduced in APOA1- or APOE
      deficient mice. The late-eluting peak was modestly reduced in APOA1-deficient
      mice but little affected in APOE- or APOA4-deficient mice. Ion-exchange
      chromatography and shotgun proteomics suggested that plasminogen (PLG) accounted
      for a substantial fraction of the ABCA1 CEC activity in the peak not associated
      with HDL. Human PLG promoted cholesterol efflux by the ABCA1 pathway, and PLG
      dependent efflux was inhibited by lipoprotein(a) [Lp(a)]. Our observations
      identify APOA1, APOE, and PLG as key determinants of CEC. Because PLG and Lp(a)
      associate with human CVD risk, interplay among the proteins might affect
      atherosclerosis by regulating cholesterol efflux from macrophages.

PMID- 28768902
TI  - Mixed-lineage kinase 3 pharmacological inhibition attenuates murine nonalcoholic
      steatohepatitis.
AB  - With the increase in obesity worldwide, its associated comorbidities, including
      nonalcoholic steatohepatitis (NASH), have become a public health problem that
      still lacks effective therapy. We have previously reported that mixed-lineage
      kinase 3-deficient (MLK3-deficient) mice are protected against diet-induced NASH.
      Given the critical need to identify new therapeutic agents, we sought to examine
      whether the small-molecule MLK3 inhibitor URMC099 would be effective in reversing
      diet-induced murine NASH. C57BL/6J mice were fed either a diet high in saturated
      fat, fructose, and cholesterol (FFC), or a chow diet for 24 weeks. Mice were
      treated with either URMC099 (10 mg/kg) twice daily by intraperitoneal injection
      or its vehicle during the last 2 weeks of the feeding study. FFC-fed mice
      receiving URMC099 had similar body weight, caloric intake, homeostatic model
      assessment of insulin resistance, metabolic phenotype, and hepatic steatosis
      compared with vehicle-treated mice. Furthermore, FFC-fed mice treated with
      URMC099 had less hepatic macrophage infiltration, activation, and proinflammatory
      polarization, as well as less liver injury and fibrosis when compared with
      vehicle-treated mice. In conclusion, URMC099 is well tolerated in mice without
      obvious toxicities and appears to be efficacious in reversing diet-induced NASH.
      Hence, URMC099 may serve as a therapeutic agent in human NASH.

PMID- 28768903
TI  - microRNA-143/145 loss induces Ras signaling to promote aggressive Pten-deficient
      basal-like breast cancer.
AB  - The tumor suppressor PTEN is frequently inactivated in breast and other cancers;
      yet, germ-line mutations in this gene induce nonmalignant hamartomas, indicating
      dependency on additional cooperating events. Here we show that most tumors
      derived from conditional deletion of mouse pten in mammary epithelium are highly
      differentiated and lack transplantable tumor-initiating cells (TICs) capable of
      seeding new tumors following orthotopic injection of FACS-sorted or tumorsphere
      cells. A rare group of poorly differentiated tumors did harbor transplantable
      TICs. These transplantable tumors exhibited distinct molecular classification,
      signaling pathways, chromosomal aberrations, and mutational landscape, as well as
      reduced expression of microRNA-143/145 (miR-143/145). Stable knockdown of miR
      143/145 conferred tumorigenic potential upon poorly transplantable pten-deficient
      tumor cells through a mechanism involving induction of RAS signaling, leading to
      increased sensitivity to MEK inhibition. In humans, miR-145 deficiency
      significantly correlated with elevated RAS-pathway activity in basal-like breast
      cancer, and patients with combined PTEN/miR-145 loss or PTEN-loss/high RAS
      pathway activity exhibited poor clinical outcome. These results underscore a
      selective pressure for combined PTEN loss together with RAS-pathway activation,
      either through miR-145 loss or other mechanisms, in basal-like breast cancer, and
      a need to identify and prioritize these tumors for aggressive therapy.

PMID- 28768904
TI  - Mapping the clinical outcomes and genetic evolution of Ebola virus in Sierra
      Leone.
AB  - Sierra Leone was the most severely affected country in Western Africa during the
      2013-2016 outbreak of Ebola virus disease (EVD). Previous genome surveillance
      studies have revealed the origin, diversity, and evolutionary dynamics of the
      Ebola virus (EBOV); however, the information regarding EBOV sequences is
      insufficient, especially the clinical outcomes, given that the correlation
      between the clinical outcomes and the genetic evolution of EBOV is still not
      clear. Here, we collected and curated a comprehensive data set that includes 514
      EBOV genome sequences from patients with confirmed EVD (including 60 sequences
      not previously studied), >87.5% of which have residence information and
      definitive clinical outcomes. Phylogenetic reconstruction revealed 11 lineages of
      EBOV in Sierra Leone. The median-joining haplotype network showed that haplotypes
      that are associated with lethal outcomes tend to contribute more to the spread of
      the EBOV in Sierra Leone than those with live outcomes. Analyses of the spatial
      temporal distribution unraveled the lineage-distinctive distribution patterns.
      Different viral lineages have different case fatality rates (CFRs) during the
      same stage of the outbreak, implying that several lineages featuring SNPs may
      correlate with increased/decreased CFRs. This study provides invaluable data sets
      of EBOV infection and highlights the potential SNPs for further in-depth
      investigation.

PMID- 28768905
TI  - Ectopic expression of Cdk8 induces eccentric hypertrophy and heart failure.
AB  - Widespread changes in cardiac gene expression occur during heart failure, yet the
      mechanisms responsible for coordinating these changes remain poorly understood.
      The Mediator complex represents a nodal point for modulating transcription by
      bridging chromatin-bound transcription factors with RNA polymerase II activity;
      it is reversibly regulated by its cyclin-dependent kinase 8 (Cdk8) kinase
      submodule. Here, we identified increased Cdk8 protein expression in human failing
      heart explants and determined the consequence of this increase in cardiac
      specific Cdk8-expressing mice. Transgenic Cdk8 overexpression resulted in
      progressive dilated cardiomyopathy, heart failure, and premature lethality. Prior
      to functional decline, left ventricular cardiomyocytes were dramatically
      elongated, with disorganized transverse tubules and dysfunctional calcium
      handling. RNA sequencing results showed that myofilament gene isoforms not
      typically expressed in adult cardiomyocytes were enriched, while oxidative
      phosphorylation and fatty acid biosynthesis genes were downregulated.
      Interestingly, candidate upstream transcription factor expression levels and MAPK
      signaling pathways thought to determine cardiomyocyte size remained relatively
      unaffected, suggesting that Cdk8 functions within a novel growth regulatory
      pathway. Our findings show that manipulating cardiac gene expression through
      increased Cdk8 levels is detrimental to the heart by establishing a
      transcriptional program that induces pathological remodeling and eccentric
      hypertrophy culminating in heart failure.

PMID- 28768906
TI  - Integration of homeostatic signaling and food reward processing in the human
      brain.
AB  - BACKGROUND: Food intake is guided by homeostatic needs and by the reward value of
      food, yet the exact relation between the two remains unclear. The aim of this
      study was to investigate the influence of different metabolic states and hormonal
      satiety signaling on responses in neural reward networks. METHODS: Twenty-three
      healthy participants underwent functional magnetic resonance imaging while
      performing a task distinguishing between the anticipation and the receipt of
      either food- or monetary-related reward. Every participant was scanned twice in a
      counterbalanced fashion, both during a fasted state (after 24 hours fasting) and
      satiety. A functional connectivity analysis was performed to investigate the
      influence of satiety signaling on activation in neural reward networks. Blood
      samples were collected to assess hormonal satiety signaling. RESULTS: Fasting was
      associated with sensitization of the striatal reward system to the anticipation
      of food reward irrespective of reward magnitude. Furthermore, during satiety,
      individual ghrelin levels were associated with increased neural processing during
      the expectation of food-related reward. CONCLUSIONS: Our findings show that
      physiological hunger stimulates food consumption by specifically increasing
      neural processing during the expectation (i.e., incentive salience) but not the
      receipt of food-related reward. In addition, these findings suggest that ghrelin
      signaling influences hedonic-driven food intake by increasing neural reactivity
      during the expectation of food-related reward. These results provide insights
      into the neurobiological underpinnings of motivational processing and hedonic
      evaluation of food reward. TRIAL REGISTRATION: ClinicalTrials.gov NCT03081585.
      FUNDING: This work was supported by the German Competence Network on Obesity,
      which is funded by the German Federal Ministry of Education and Research (FKZ
      01GI1122E).

PMID- 28768907
TI  - Upregulated heme biosynthesis, an exploitable vulnerability in MYCN-driven
      leukemogenesis.
AB  - The increased heme biosynthesis long observed in leukemia was previously of
      unknown significance. Heme, synthesized from porphyrin precursors, plays a
      central role in oxygen metabolism and mitochondrial function, yet little is known
      about its role in leukemogenesis. Here, we show increased expression of heme
      biosynthetic genes, including UROD, only in pediatric AML samples that have high
      MYCN expression. High expression of both UROD and MYCN predicts poor overall
      survival and unfavorable outcomes in adult AML. Murine leukemic progenitors
      derived from hematopoietic progenitor cells (HPCs) overexpressing a MYCN cDNA
      (MYCN-HPCs) require heme/porphyrin biosynthesis, accompanied by increased oxygen
      consumption, to fully engage in self-renewal and oncogenic transformation.
      Blocking heme biosynthesis reduced mitochondrial oxygen consumption and markedly
      suppressed self-renewal. Leukemic progenitors rely on balanced production of heme
      and heme intermediates, the porphyrins. Porphyrin homeostasis is required because
      absence of the porphyrin exporter, ABCG2, increased death of leukemic progenitors
      in vitro and prolonged the survival of mice transplanted with Abcg2-KO MYCN-HPCs.
      Pediatric AML patients with elevated MYCN mRNA display strong activation of TP53
      target genes. Abcg2-KO MYCN-HPCs were rescued from porphyrin toxicity by p53
      loss. This vulnerability was exploited to show that treatment with a porphyrin
      precursor, coupled with the absence of ABCG2, blocked MYCN-driven leukemogenesis
      in vivo, thereby demonstrating that porphyrin homeostasis is a pathway crucial to
      MYCN leukemogenesis.

PMID- 28768908
TI  - Nonmyocyte ERK1/2 signaling contributes to load-induced cardiomyopathy in Marfan
      mice.
AB  - Among children with the most severe presentation of Marfan syndrome (MFS), an
      inherited disorder of connective tissue caused by a deficiency of extracellular
      fibrillin-1, heart failure is the leading cause of death. Here, we show that,
      while MFS mice (Fbn1C1039G/+ mice) typically have normal cardiac function,
      pressure overload (PO) induces an acute and severe dilated cardiomyopathy in
      association with fibrosis and myocyte enlargement. Failing MFS hearts show high
      expression of TGF-beta ligands, with increased TGF-beta signaling in both
      nonmyocytes and myocytes; pathologic ERK activation is restricted to the
      nonmyocyte compartment. Informatively, TGF-beta, angiotensin II type 1 receptor
      (AT1R), or ERK antagonism (with neutralizing antibody, losartan, or MEK
      inhibitor, respectively) prevents load-induced cardiac decompensation in MFS
      mice, despite persistent PO. In situ analyses revealed an unanticipated axis of
      activation in nonmyocytes, with AT1R-dependent ERK activation driving TGF-beta
      ligand expression that culminates in both autocrine and paracrine overdrive of
      TGF-beta signaling. The full compensation seen in wild-type mice exposed to mild
      PO correlates with enhanced deposition of extracellular fibrillin-1. Taken
      together, these data suggest that fibrillin-1 contributes to cardiac reserve in
      the face of hemodynamic stress, critically implicate nonmyocytes in disease
      pathogenesis, and validate ERK as a therapeutic target in MFS-related cardiac
      decompensation.

PMID- 28768909
TI  - Addressing metabolic heterogeneity in clear cell renal cell carcinoma with
      quantitative Dixon MRI.
AB  - BACKGROUND: Dysregulated lipid and glucose metabolism in clear cell renal cell
      carcinoma (ccRCC) has been implicated in disease progression, and whole tumor
      tissue-based assessment of these changes is challenged by the tumor
      heterogeneity. We studied a noninvasive quantitative MRI method that predicts
      metabolic alterations in the whole tumor. METHODS: We applied Dixon-based MRI for
      in vivo quantification of lipid accumulation (fat fraction [FF]) in targeted
      regions of interest of 45 primary ccRCCs and correlated these MRI measures to
      mass spectrometry-based lipidomics and metabolomics of anatomically colocalized
      tissue samples isolated from the same tumor after surgery. RESULTS: In vivo tumor
      FF showed statistically significant (P < 0.0001) positive correlation with
      histologic fat content (Spearman correlation coefficient, rho = 0.79),
      spectrometric triglycerides (rho = 0.56) and cholesterol (rho = 0.47); it showed
      negative correlation with free fatty acids (rho = -0.44) and phospholipids (rho =
      -0.65). We observed both inter- and intratumoral heterogeneity in lipid
      accumulation within the same tumor grade, whereas most aggressive tumors
      (International Society of Urological Pathology [ISUP] grade 4) exhibited reduced
      lipid accumulation. Cellular metabolites in tumors were altered compared with
      adjacent renal parenchyma. CONCLUSION: Our results support the use of noninvasive
      quantitative Dixon-based MRI as a biomarker of reprogrammed lipid metabolism in
      ccRCC, which may serve as a predictor of tumor aggressiveness before surgical
      intervention. FUNDING: NIH R01CA154475 (YZ, MF, PK, IP), NIH P50CA196516 (IP, JB,
      RJD, JAC, PK), Welch Foundation I-1832 (JY), and NIH P01HL020948 (JGM).

PMID- 28768910
TI  - Sexual dimorphism in glioma glycolysis underlies sex differences in survival.
AB  - The molecular bases for sex differences in cancer remain undefined and how to
      incorporate them into risk stratification remains undetermined. Given sex
      differences in metabolism and the inverse correlation between fluorodeoxyglucose
      (FDG) uptake and survival, we hypothesized that glycolytic phenotyping would
      improve glioma subtyping. Using retrospectively acquired lower-grade glioma (LGG)
      transcriptome data from The Cancer Genome Atlas (TCGA), we discovered male
      specific decreased survival resulting from glycolytic gene overexpression.
      Patients within this high-glycolytic group showed significant differences in the
      presence of key genomic alterations (i.e., 1p/19q codeletion, CIC, EGFR, NF1,
      PTEN, FUBP1, and IDH mutations) compared with the low-glycolytic group. Although
      glycolytic stratification defined poor prognostic males independent of grade,
      histology, TP53, and ATRX mutation status, we unexpectedly found that females
      with high-glycolytic gene expression and wild-type IDH survived longer than all
      other wild-type patients. Validation with an independent metabolomics dataset
      from grade 2 gliomas determined that glycolytic metabolites selectively
      stratified males and also uncovered a potential sexual dimorphism in pyruvate
      metabolism. These findings identify a potential synergy between patient sex,
      tumor metabolism, and genomic alterations in determining outcome for glioma
      patients.

PMID- 28768911
TI  - A CCR2+ myeloid cell niche required for pancreatic beta cell growth.
AB  - Organ-specific patterns of myeloid cells may contribute tissue-specific growth
      and/or regenerative potentials. The perinatal stage of pancreas development marks
      a time characterized by maximal proliferation of pancreatic islets, ensuring the
      maintenance of glucose homeostasis throughout life. Ontogenically distinct
      CX3CR1+ and CCR2+ macrophage populations have been reported in the adult
      pancreas, but their functional contribution to islet cell growth at birth remains
      unknown. Here, we uncovered a temporally restricted requirement for CCR2+ myeloid
      cells in the perinatal proliferation of the endocrine pancreatic epithelium.
      CCR2+ macrophages are transiently enriched over CX3CR1+ subsets in the neonatal
      pancreas through both local expansion and recruitment of immature precursors.
      Using CCR2-specific depletion models, we show that loss of this myeloid
      population leads to a striking reduction in beta cell proliferation,
      dysfunctional islet phenotypes, and glucose intolerance in newborns.
      Replenishment of pancreatic CCR2+ myeloid compartments by adoptive transfer
      rescues these defects. Gene profiling identifies pancreatic CCR2+ myeloid cells
      as a prominent source of IGF2, which contributes to IGF1R-mediated islet
      proliferation. These findings uncover proproliferative functions of CCR2+ myeloid
      subsets and identify myeloid-dependent regulation of IGF signaling as a local cue
      supporting pancreatic proliferation.

PMID- 28768912
TI  - Single-cell profiling reveals GPCR heterogeneity and functional patterning during
      neuroinflammation.
AB  - GPCR expression was intensively studied in bulk cDNA of leukocyte populations,
      but limited data are available with respect to expression in individual cells.
      Here, we show a microfluidic-based single-cell GPCR expression analysis in
      primary T cells, myeloid cells, and endothelial cells under naive conditions and
      during experimental autoimmune encephalomyelitis, the mouse model of multiple
      sclerosis. We found that neuroinflammation induces characteristic changes in GPCR
      heterogeneity and patterning, and we identify various functionally relevant
      subgroups with specific GPCR profiles among spinal cord-infiltrating CD4 T cells,
      macrophages, microglia, or endothelial cells. Using GPCRs CXCR4, S1P1, and LPHN2
      as examples, we show how this information can be used to develop new strategies
      for the functional modulation of Th17 cells and activated endothelial cells.
      Taken together, single-cell GPCR expression analysis identifies functionally
      relevant subpopulations with specific GPCR repertoires and provides a basis for
      the development of new therapeutic strategies in immune disorders.

PMID- 28768913
TI  - HIV-1 selectively targets gut-homing CCR6+CD4+ T cells via mTOR-dependent
      mechanisms.
AB  - Gut-associated lymphoid tissues are enriched in CCR6+ Th17-polarized CD4+ T cells
      that contribute to HIV-1 persistence during antiretroviral therapy (ART). This
      raises the need for Th17-targeted immunotherapies. In an effort to identify
      mechanisms governing HIV-1 permissiveness/persistence in gut-homing Th17 cells,
      we analyzed the transcriptome of CCR6+ versus CCR6- T cells exposed to the gut
      homing inducer retinoic acid (RA) and performed functional validations in colon
      biopsies of HIV-infected individuals receiving ART (HIV+ART). Although both CCR6+
      and CCR6- T cells acquired gut-homing markers upon RA exposure, the modulation of
      unique sets of genes coincided with preferential HIV-1 replication in RA-treated
      CCR6+ T cells. This molecular signature included the upregulation of HIV
      dependency factors acting at entry/postentry levels, such as the CCR5 and
      PI3K/Akt/mTORC1 signaling pathways. Of note, mTOR expression/phosphorylation was
      distinctively induced by RA in CCR6+ T cells. Consistently, mTOR inhibitors
      counteracted the effect of RA on HIV replication in vitro and viral reactivation
      in CD4+ T cells from HIV+ART individuals via postentry mechanisms independent of
      CCR5. Finally, CCR6+ versus CCR6- T cells infiltrating the colons of HIV+ART
      individuals expressed unique molecular signatures, including higher levels of
      CCR5, integrin beta7, and mTOR phosphorylation. Together, our results identify
      mTOR as a druggable key regulator of HIV permissiveness in gut-homing CCR6+ T
      cells.

PMID- 28768914
TI  - Dichotomous miR expression and immune responses following primary blood-stage
      malaria.
AB  - Clinical responses to infection or vaccination and the development of effective
      immunity are characterized in humans by a marked interindividual variability. To
      gain an insight into the factors affecting this variability, we used a controlled
      human infection system to study early immune events following primary infection
      of healthy human volunteers with blood-stage Plasmodium falciparum malaria. By
      day 4 of infection, a dichotomous pattern of high or low expression of a defined
      set of microRNAs (miRs) emerged in volunteers that correlated with variation in
      parasite growth rate. Moreover, high-miR responders had higher numbers of
      activated CD4+ T cells, and developed significantly enhanced antimalarial
      antibody responses. Notably, a set of 17 miRs was identified in the whole blood
      of low-miR responders prior to infection that differentiated them from high-miR
      responders. These data implicate preexisting host factors as major determinants
      in the ability to effectively respond to primary malaria infection.

PMID- 28768915
TI  - TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy.
AB  - Myocardial atrophy is a wasting of cardiac muscle due to hemodynamic unloading.
      Doxorubicin is a highly effective anticancer agent but also induces myocardial
      atrophy through a largely unknown mechanism. Here, we demonstrate that inhibiting
      transient receptor potential canonical 3 (TRPC3) channels abolishes doxorubicin
      induced myocardial atrophy in mice. Doxorubicin increased production of ROS in
      rodent cardiomyocytes through hypoxic stress-mediated upregulation of NADPH
      oxidase 2 (Nox2), which formed a stable complex with TRPC3. Cardiomyocyte
      specific expression of TRPC3 C-terminal minipeptide inhibited TRPC3-Nox2 coupling
      and suppressed doxorubicin-induced reduction of myocardial cell size and left
      ventricular (LV) dysfunction, along with its upregulation of Nox2 and oxidative
      stress, without reducing hypoxic stress. Voluntary exercise, an effective
      treatment to prevent doxorubicin-induced cardiotoxicity, also downregulated the
      TRPC3-Nox2 complex and promoted volume load-induced LV compliance, as
      demonstrated in TRPC3-deficient hearts. These results illustrate the impact of
      TRPC3 on LV compliance and flexibility and, focusing on the TRPC3-Nox2 complex,
      provide a strategy for prevention of doxorubicin-induced cardiomyopathy.

PMID- 28768917
TI  - Efficacy and Safety of Switching From Oral Bisoprolol to Transdermal Patch in
      Japanese Patients With Chronic Heart Failure.
AB  - BACKGROUND: TY-0201 (TY) is a transdermal formulation of bisoprolol that is the
      free base of bisoprolol fumarate (BO), a drug widely used to treat chronic heart
      failure (CHF). The objectives of this phase II study were to evaluate the
      efficacy and safety of TY when switching from oral BO to TY in patients with CHF
      whose drug therapy was optimized, and to determine the dose conversion rate of BO
      to TY.Methods and Results:The efficacy and safety of once daily TY patch use for
      16 weeks was investigated in 40 patients with CHF who were stabilized with an
      optimized drug treatment, including BO, after switching from BO to TY at the dose
      conversion rate of 5:8. The pre-switch left ventricular ejection fraction was
      50.13+/-11.09% (mean+/-SD). The post-switch value was 50.87+/-10.79% after 16
      weeks, which was not significantly different, with similar results for other
      efficacy and safety parameters. The 16-week study was continued for all patients
      without changing doses after switching to TY. No cardiovascular deaths,
      hospitalizations for worsening HF, or significant safety concerns were observed.
      CONCLUSIONS: Efficacy was maintained without significant safety concerns in
      patients with CHF who were stabilized with BO treatment after switching to TY,
      suggesting the appropriateness of the dose conversion rate.

PMID- 28768916
TI  - High pathogen burden in childhood promotes the development of unconventional
      innate-like CD8+ T cells.
AB  - Cellular and humoral constituents of the immune system differ significantly
      between children and adults, yet very little is known about the impact of early
      life pathogen exposure on this immunologic transition. We examined CD4+ and CD8+
      T cell subsets defined by CCR7 and CD45RA expression in two longitudinal
      pediatric cohorts experiencing divergent levels of pathogen burden. Using
      multiparameter flow cytometry, along with serological, cytokine, and
      transcriptomic data, we show that cumulative pathogen burden promotes the
      development of atypical CD8dim T cells with an innate-like profile (Granzyme Bhi,
      IFNgammalow, TNFalphalow, PLFZhi, ID2hi, IKZF2hi) in contrast to age-matched
      children residing in a low pathogen-exposure area who display a more conventional
      CD8bright profile (IFNgamma+, TNFalpha+, CCL4+). Furthermore, these
      unconventional T cells had stunted proliferation, distinct transcriptional
      programs, and impaired T cell receptor signaling and were enriched in hallmark
      TNFalpha, NF-kappaB, and IL-6 gene signaling pathways, reminiscent of NK cells
      and type-1 innate lymphoid cells. Our findings suggest that these unconventional
      CD8dim T cells arise in a very particular immunological context and may provide a
      deeper understanding of the heterogeneity in human immune responses.

PMID- 28768918
TI  - Advantages and Disadvantages of Multi-axis Intraoperative Angiography Unit for
      Percutaneous Pedicle Screw Placement in the Lumbar Spine.
AB  - We analyzed clinical usefulness of the high resolution imaging system in a hybrid
      operation room (OR) for posterior lumbar interbody fusion. A total of 17 patients
      with lumbar spondylolisthesis between February 2014 and August 2016 were
      included. Multi-axis imaging system in a hybrid OR was used in 12 patients
      (hybrid OR group); the conventional C-arm fluoroscopy, in 5 patients (C-arm
      group). The time to confirm the first percutaneous pedicle screw (PPS) angle
      (hybrid OR, 80 vs C-arm, 249 s; P = 0.0026) and the second to the last PPS angle
      (77 vs 90 s; P = 0.040) were shorter in the hybrid OR group. Placement accuracy
      was higher in the hybrid OR group (88.0 vs 59.1%; P = 0.010). Irradiation dose
      was significantly lower in the C-arm group (462 vs 102 mGy; P = 0.0013). This
      study suggested that the accuracy of PPS placement and time to confirm the PPS
      angle are the advantages in a hybrid OR.

PMID- 28768919
TI  - Pediatric Craniovertebral Junction Surgery.
AB  - The craniovertebral junction (CVJ) has attracted more attention in pediatric
      medicine in recent years due to the progress in surgical technologies allowing a
      direct approach to the CVJ in children. The CVJ is the site of numerous
      pathologies, most originating in bone anomalies resulting from abnormal CVJ
      development. Before discussing the surgical approaches to CVJ, three points
      should be borne in mind: first, that developmental anatomy demonstrates age
      dependent mechanisms and the pathophysiology of pediatric CVJ anomalies; second,
      that CT-based dynamic simulations have improved our knowledge of functional
      anatomy, enabling us to locate CVJ lesions with greater certainty; and third,
      understanding the complex structure of the pediatric CVJ also clarifies the
      surgical anatomy. This review begins with a description of the embryonic
      developmental process of the CVJ, comprising ossification and resegmentation of
      the somite. From the clinical perspective, pediatric CVJ lesions can be divided
      into three categories: developmental bony anomalies with or without instability,
      stenotic CVJ lesions, and others. After discussing surgery and management based
      on this classification, the author describes surgical outcomes on his hands, and
      finally proceeds to address controversial issues specific for pediatric CVJ
      surgery. The lessons, which the author has gleaned from his experience in
      pediatric CVJ surgery, are also presented briefly in this review. Recent
      technological progress has facilitated pediatric surgery of the CVJ. However, it
      is important to recognize that we are still far from reliably and consistently
      obtaining satisfactory results. Further progress in this area awaits
      contributions of the coming generations of pediatric surgeons.

PMID- 28768921
TI  - Efficacy and Safety of the Cholesteryl Ester Transfer Protein Inhibitor
      Evacetrapib in Combination With Atorvastatin in Japanese Patients With Primary
      Hypercholesterolemia.
AB  - BACKGROUND: Inhibition of cholesteryl ester transfer protein by evacetrapib when
      added to atorvastatin may provide an additional treatment option for patients who
      do not reach their low-density lipoprotein cholesterol (LDL-C) goal.Methods and
      Results:This multicenter, randomized, 12-week, double-blind, parallel-group,
      placebo-controlled, outpatient, phase 3 study evaluated the efficacy of
      evacetrapib with atorvastatin in reducing LDL-C in 149 Japanese patients
      (evacetrapib/atorvastatin, n=53; ezetimibe/atorvastatin, n=50;
      placebo/atorvastatin, n=46) with primary hypercholesterolemia. The primary
      efficacy measure was percent change from baseline to week 12 in LDL-C (beta
      quantification). Treatment with evacetrapib 130 mg daily for 12 weeks resulted in
      a statistically significant treatment difference of -25.70% compared with placebo
      in percentage decrease in LDL-C (95% CI: -34.73 to -16.68; P<0.001). Treatment
      with evacetrapib 130 mg also resulted in a statistically significant difference
      of 126.39% in the change in high-density lipoprotein cholesterol (HDL-C) compared
      with placebo (95% CI: 113.54-139.24; P<0.001). No deaths or serious adverse
      events were reported. Four patients (3 in the evacetrapib group and 1 in the
      ezetimibe group) discontinued due to adverse events. CONCLUSIONS: Evacetrapib
      daily in combination with atorvastatin was superior to placebo in lowering LDL-C
      after 12 weeks, and resulted in a statistically significant increase of HDL-C
      compared with placebo. Also, no new safety risks were identified.

PMID- 28768920
TI  - Neuronavigation-guided Frameless Stereoelectroencephalography (SEEG).
AB  - Stereoelectroencephalography (SEEG) is an invasive surgical procedure used to
      identify epileptogenic zones. The combination of both subdural grids and depth
      electrodes (DEs) is currently used for invasive intracranial monitoring in many
      epilepsy centers. To perform DE implantation, some centers use frame-based
      stereotactic techniques and others use stereotactic robotic techniques. However,
      not all epilepsy centers have access to these tools. We hypothesized that DE
      implantation using a neuronavigation system can be utilized for subsequent
      epilepsy surgery. Between April 2016 and April 2017, we performed invasive
      monitoring for 26 patients. Among these, 17 patients (8 females, 9 males; mean
      age, 21.2 years; range, 3-51 years) underwent DE implantation. We divided
      patients into three groups: Group 1 (7 patients), a free-hand implantation group;
      Group 2 (7 patients), a frameless stereotactic implantation group; and Group 3 (3
      patients), a computed tomography (CT)-guided auto image registration system with
      the stereotactic implantation group. Group 3 showed the closest distance from
      planned target to DE tip, followed by Group 2. Fourteen of the 17 patients
      underwent subsequent epilepsy surgery referring to the results of DE studies. DE
      placement using a neuronavigation system without stereotactic robotic equipment
      or frame-based stereotactic techniques can be utilized for subsequent epilepsy
      surgery.

PMID- 28768922
TI  - Preoperative Assessment of Endothelial Function for Prediction of Adverse Events
      After Cardiovascular Surgery.
AB  - BACKGROUND: Cardiovascular surgery is one of the highest risk procedures in the
      field of surgery. Preoperative assessment of endothelial function has been
      reported as useful for predicting postoperative adverse events (AEs). The aim of
      this study was to investigate the relationship between endothelial function
      assessed by reactive hyperemia index (RHI) and AEs after cardiovascular
      surgery.Methods and Results:A prospective observational study of 197 patients who
      underwent cardiovascular surgery was conducted. RHI was measured before the
      surgery. The primary endpoint was a composite of postoperative death,
      reoperation, stroke, newly required dialysis, deep sternum infection, and
      prolonged ventilation within 30 days. The secondary endpoint was new-onset atrial
      fibrillation (AF) within 30 days. Following cardiovascular surgery, 19 patients
      (9.6%) had AEs. New-onset AF was documented in 42 (25.9%) of 162 patients without
      a prior history of AF. In the receiver-operating characteristic curve analysis,
      RHI significantly predicted AEs (area under the curve [AUC] 0.67, best cutoff
      value 1.64, P=0.03), whereas RHI did not predict new-onset AF (AUC 0.53, P=0.93).
      Patients with RHI <=1.64 had more AEs than those with RHI >1.64 (16.3% vs. 4.5%,
      P=0.005). Multiple logistic regression analysis showed the number of surgical
      procedures and RHI <=1.64 as significant predictors of AEs. CONCLUSIONS:
      Preoperative endothelial dysfunction assessed by RHI was associated with
      postoperative AEs in patients with cardiovascular surgery.

PMID- 28768923
TI  - Conservation and Divergence of Ligand Recognition and Signal Transduction
      Mechanisms in Toll-Like Receptors.
AB  - Toll-like receptors (TLRs) play a central role in innate immunity as pathogen
      sensors. During the last decade, structural analyses of TLRs have revealed the
      mechanisms of ligand recognition and signal transduction. Each TLR recognizes its
      cognate ligand in a different manner, whereas signal transduction is achieved by
      a common mechanism. In this review, the mechanisms of ligand recognition and
      signal transduction by TLRs are summarized based on recent structural
      information.

PMID- 28768924
TI  - A Novel High Throughput Virtual Screening Protocol to Discover New Indoleamine
      2,3-Dioxygenase 1 (IDO1) Inhibitors.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) plays an important role in the immune escape
      of tumors and has emerged as a promising target for cancer immunotherapy. Despite
      its potential in immuno-oncology, very few chemotypes have been reported to date.
      Here, we disigned a novel high throughput virtual screening (HTVS) cascade
      protocol, combining both pharmacophore modeling and molecular docking and it was
      employed to query commercially available compounds to identify novel inhibitors.
      Among the 23 compounds selected for the in vitro IDO1 inhibitory activity assay,
      five compounds exhibit greater than 20% inhibition at a test concentration of 10
      uM, with two compounds having an IC50 value of 23.8 and 8.8 uM, respectively. The
      novel scaffold together with a ligand efficiency of 0.28 kcal/mol per heavy atom
      makes both compounds as suitable starting points for future chemistry
      elaboration. Our HTVS protocol was validated and could be employed in discovery
      of IDO1 inhibitors.

PMID- 28768925
TI  - Reduction-Sensitive Poly(ethylenimine) Nanogel Bearing Dithiodipropionic Acid.
AB  - Reduction-sensitive nanogel was developed by including dithiodipropionic acid
      (DTPA) in tripolyphosphoric acid (TPPA) cross-linked poly(ethylenimine) (PEI)
      nanogel. According to the light scattering measurement, DTPA (a disulfide
      compound) seemed to cross-link PEI chains in a cooperative manner with TPPA (a
      multi-valent anion). Nanogels composed of TPPA, PEI, and DTPA exhibited negative
      zeta potential and the absolute value increased with the amount of TPPA and DTPA.
      TPPA and DTPA were found to be contained in the nanogel, evidenced by Fourier
      transform (FT)-IR spectroscopy and Raman spectroscopy, respectively. 1H-NMR
      spectroscopy also revealed DTPA was contained in the nanogel. The DTPA content in
      the nanogel was determined colorimetrically to be 7.14 and 9.4%, depending on the
      DTPA content in the raw mixture for the preparation of nanogel. On the
      transmission electron microscopy (TEM) micrographs of the negatively stained
      nanogel, the diameter was about 20-30 nm. The specific loading of carboxylic
      fluorescein (CF) in the nanogel was around 1.8%, determined by fluorometric
      analysis, and it was not affected by the DTPA content. The maximum release degree
      of CF loaded in nanogel containing no DTPA was less than 10% and it was almost
      the same regardless of dithiothreitol (DTT) concentration. Whereas, the release
      of the dye loaded in nanogel containing DTPA was markedly promoted by DTT,
      possibly because the disulfide bond can be broken by DTT and the diffusivity of
      the dye through the nanogel matrix can increase.

PMID- 28768926
TI  - Melt Adsorption as a Manufacturing Method for Fine Particles of Wax Matrices
      without Any Agglomerates.
AB  - We have focused on melt adsorption as manufacture method of wax matrices to
      control particles size of granules more easily than melt granulation. The purpose
      of present study was to investigate the possibility of identifying a hydrophobic
      material with a low melting point, currently used as a meltable binder of melt
      granulation, to apply as a novel carrier in melt adsorption. Glyceryl
      monostearate (GM) and stearic acid (SA) were selected as candidate hydrophobic
      materials with low melting points. Neusilin US2 (US2), with a particle diameter
      of around 100 um was selected as a surface adsorbent, while dibasic calcium
      phosphate dihydrate (DCPD), was used as a non-adsorbent control to prepare
      melting granules as a standard for comparison. We prepared granules containing
      ibuprofen (IBU) by melt adsorption or melt granulation and evaluated the particle
      size, physical properties and crystallinity of granules. Compared with melt
      granulation using DCPD, melt adsorption can be performed over a wide range of 14
      to 70% for the ratio of molten components. Moreover, the particle size; d50 of
      obtained granules was 100-200 um, and these physical properties showed good
      flowability and roundness. The process of melt adsorption did not affect the
      crystalline form of IBU. Therefore, the present study has demonstrated for the
      first time that melt adsorption using a hydrophobic material, GM or SA, has the
      potential capability to control the particle size of granules and offers the
      possibility of application as a novel controlled release technique.

PMID- 28768927
TI  - Synthesis and Biological Evaluation of New Tacrine Analogues under Microwave
      Irradiation.
AB  - Efficient routes to various kinds of heterocycles incorporating the p-halophenyl
      moiety have been synthesized. Different pyrrole derivatives have been
      synthesized, as well, by Thorpe-Ziegler cyclization. Therefore, we synthesized
      different analogues of tacrine by Friedlander reaction of o-amino nitriles
      (pyrazolo, furano and pyrrolo) with different cycloalkanones. The use of
      microwave irradiation leads to shorter production times and high product
      conversion. These synthesized compounds were biologically evaluated by Ellman's
      test on acetylcholinesterase inhibition.

PMID- 28768928
TI  - Naphthoquinone Derivatives from Diospyros maritima.
AB  - From the chloroform extract of the fresh fruits of Diospyros maritima BLUME
      (Ebenaceae), five new naphthoquinone derivatives, 2,7'-dimethyl-2',3-bijuglone
      (27), 2,7'-dimethyl-3,3'-bijuglone (28), 2,7'-dimethyl-6,8'-bijuglone (29), 7,7'
      dimethyl-3,3'-ethylidenebijuglone (30), and 2',7-dimethyl-3,6'
      ethylidenebijuglone (31), were isolated, in addition to twenty-one known
      naphthoquinone derivatives: plumbagin (4), droserone (5), 2,3-epoxyplumbagin (8),
      3,3'-biplumbagin (9), chitranone (10), 3,8'-biplumbagin (11), elliptinone (12),
      maritinone (13), isozeylanone (14), methylene-3,3'-biplumbagin (15), ethylidene
      3,3'-biplumbagin (16), ethylidene-3,6'-biplumbagin (17), ethylidene-6,6'
      biplumbagin (18), 7-methyl-beta-dihydrojuglone (19), 7-methyljuglone (20), 2,3
      epoxy-7-methyljuglone (21), neodiospyrin (22), mamegakinone (23), ehretione (24),
      isoxylospyrin (25) and beta-dihydroplumbagin (26). The structures of the new
      compounds were established by spectral analysis. The quinones obtained from the
      chloroform extract of the fruits were compared with previously reported quinones
      obtained from ethanol extracts. The quinones in the fruits were categorized in
      three groups: quinones from ethanol extract only, quinones from chloroform
      extract only, and quinones from both extracts. The six naphthoquinones, 19-21,
      25, 26, and 29, were examined for their ichthyotoxic activity and germination
      inhibitory activity. Quinones 19-21, 26, and 29 showed ichthyotoxic activity
      against Japanese killifish (Oryzias latipes var.) at 10 ppm; quinones 19 to 21
      and 26 showed germination inhibitory activity toward lettuce seeds (Lactuca
      sativa L. var. Great Lakes) at 100 ppm.

PMID- 28768929
TI  - Aliphatic Glucoside, Zanthoionic Acid and Megastigmane Glucosides:
      Zanthoionosides A-E from the Leaves of Zanthoxylum ailanthoides.
AB  - From the leaves of Zanthoxylum ailanthoides, 4'-O-p-E-coumaric acid esters of 2
      propanol beta-D-glucopyranoside, megastigmane and megastigmane glucosides were
      isolated. Their structures were elucidated by spectroscopic evidence. The
      absolute configurations of the megastigmane and aglycone of megastigmane
      glucosides were determined by the octant rule and modified Mosher's method after
      protection of carboxylic acids by p-bromophenacyl esters and primary alcohols by
      pivaloyl esters.

PMID- 28768930
TI  - Curcumin Inhibits Chondrocyte Hypertrophy of Mesenchymal Stem Cells through IHH
      and Notch Signaling Pathways.
AB  - Using tissue engineering technique to repair cartilage damage caused by
      osteoarthritis is a promising strategy. However, the regenerated tissue usually
      is fibrous cartilage, which has poor mechanical characteristics compared to
      hyaline cartilage. Chondrocyte hypertrophy plays an important role in this
      process. Thus, it is very important to find out a suitable way to maintain the
      phenotype of chondrocytes and inhibit chondrocyte hypertrophy. Curcumin deriving
      from turmeric was reported with anti-inflammatory and anti-tumor pharmacological
      effects. However, the role of curcumin in metabolism of chondrocytes, especially
      in the chondrocyte hypertrophy remains unclear. Mesenchymal stem cells (MSCs) are
      widely used in cartilage tissue engineering as seed cells. So we investigated the
      effect of curcumin on chondrogenesis and chondrocyte hypertrophy in MSCs through
      examination of cell viability, glycosaminoglycan synthesis and specific gene
      expression. We found curcumin had no effect on expression of chondrogenic markers
      including Sox9 and Col2a1 while hypertrophic markers including Runx2 and Col10a1
      were down-regulated. Further exploration showed that curcumin inhibited
      chondrocyte hypertrophy through Indian hedgehog homolog (IHH) and Notch
      signalings. Our results indicated curcumin was a potential agent in modulating
      cartilage homeostasis and maintaining chondrocyte phenotype.

PMID- 28768931
TI  - Potential of Stratum Corneum Lipid Liposomes for Screening of Chemical Skin
      Penetration Enhancers.
AB  - The evaluation of effective skin chemical penetration enhancers (CPEs) is a
      crucial process in the development of transdermal and dermal formulations with
      the capacity to overcome the stratum corneum barrier. In the present study, we
      aimed to investigate the potential of stratum corneum lipid liposomes (SCLLs) as
      an alternative tool for the screening of various types and concentrations of
      CPEs. SCLLs were prepared using a thin-film hydration technique, and two types of
      fluorescent probes (sodium fluorescein [FL] or 1,6-diphenyl-1,3,5-hexatriene
      [DPH] were entrapped separately into SCLLs (FL-SCLL and DPH-SCLL, respectively).
      FL leakage from SCLLs as well as the fluidity of DPH-SCLLs were determined after
      incubating with various types of CPEs as a function of their concentrations. The
      obtained results showed a concentration-dependent relationship for most CPEs both
      for FL leakage and the fluidity of SCLLs. When observing these data in detail,
      however, the concentration profiles could be classified into five main categories
      depending on the mode of action of the CPEs. These results strongly suggest the
      usefulness of SCLLs for high-throughput screening of effective CPEs as well as
      the understanding of their possible mode of action, especially in the early stage
      of skin formulation development.

PMID- 28768932
TI  - Efficient Synthesis of Heterocyclic Flavonoids with Hedgehog Signal Inhibitory
      Activity.
AB  - The hedgehog (Hh) signaling pathway performs important roles in embryonic
      development and cellular proliferation and differentiation. However, in many
      cancer cells Hh signaling is aberrantly activated, which has provided a strong
      impetus for the development of Hh pathway inhibitors. To address this, we
      synthesized a series of heterocyclic flavonoids and evaluated their Hh signaling
      inhibitory activity on cancer cell lines using our cell-based assay system. Of
      the synthetic flavonoids, compounds 4a and g showed good inhibitory activity
      (IC50 was 16.8 and 21.8 uM, respectively), and were cytotoxic toward human
      pancreatic (PANC1) and prostate (DU145) cancer cells in which Hh signaling was
      activated. Compounds 4a and g had moderate selectivity against PANC1 cells.
      Western blotting analyses revealed that PTCH and GLI1 expression was reduced
      after treatment with these compounds. Overall, these synthetic flavonoids
      represent promising new additions to our expanding panel of Hh pathway
      inhibitors, and with further development these molecules may ultimately be
      considered for clinical use.

PMID- 28768933
TI  - 7-Hydroxy-3-methyleneisoindolin-1-one as a New ESIPT-Fluorescent Probe to Monitor
      Aqueous Environments.
AB  - A 7-hydroxy derivative of 3-methyleneisoindolin-1-one 1 was synthesized and its
      properties as a new fluorophore undergoing excited-state intramolecular proton
      transfer (ESIPT) were investigated. In alcohols and dimethylsulfoxide, 1
      exhibited dual emission at ca. 380 and 525-540 nm when excited at ca. 336 nm,
      which agreed well with the density functional theory (DFT) and time-dependent
      (TD)-DFT-calculated emission predictions of 1 and its ESIPT tautomer. In aqueous
      solutions at near neutral pH, 1 exhibited a broad emission band at ca. 497 nm,
      presumably caused by the overlap of emissions from 1 and the excited state
      phenolate species of 1. In binary mixtures of H2O and EtOH, the wavelength and
      intensity of fluorescence maxima were dependent on the dielectric constant of the
      solvent, suggesting that 1 could be applied as a fluorescent probe to monitor
      aqueous environments.

PMID- 28768934
TI  - Chloramine-T-Mediated Oxidation of Benzylic Alcohols Using Indium(III) Triflate.
AB  - The efficient oxidation of benzylic alcohols to carbonyl compounds was performed
      using chloramine-T and a catalytic amount of indium(III) triflate. The primary
      benzylic alcohols were converted to the corresponding aldehydes in a good yield,
      and the secondary benzylic alcohols were oxidized to ketones in a high yield. The
      optimized reaction conditions required 0.3 eq of indium(III) triflate and the use
      of acetonitrile as a solvent.

PMID- 28768935
TI  - Predictors of Quality of Life Improvement after 2 Years of Coronary Artery Bypass
      Surgery.
AB  - PURPOSE: The aim was to examine the predictors of improvement of quality of life
      after 2 years of coronary artery bypass grafting (CABG). METHODS: In all, 208
      patients who underwent the elective CABG at the Institute for Cardiovascular
      Diseases Dedinje in Belgrade were contacted and examined 2 years after the
      surgery. All patients completed Nottingham Health Profile Questionnaire part one.
      RESULTS: Two years after CABG, quality of life (QOL) in patients was
      significantly improved in all sections compared to preoperative period.
      Independent predictors of QOL improvement after 2 years of CABG were found to be
      serious angina under sections of physical mobility [p = 0.003, odds ratio (OR) =
      1.76, 95% confidence interval (CI) 1.21-2.55], energy (p = 0.01, OR = 1.63, 95%
      CI: 1.11-2.38), sleep (p = 0.005, OR = 1.65, 95% CI: 1.16-2.35), pain (p <0.001,
      OR = 2.43, 95% CI: 1.57-3.77), absence of hereditary load in energy section (p =
      0.002, OR = 0.35, 95% CI: 0.18-0.68), male sex in the sleep section (p = 0.03, OR
      = 0.43, 95% CI: 0.20-0.93), and absence of diabetes in pain section (p = 0.006,
      OR = 0.27, 95% CI: 0.10-0.68). CONCLUSION: Predictors of improvement of QOL after
      2 years of CABG are serious angina, absence of hereditary load, male sex, and
      absence of diabetes.

PMID- 28768936
TI  - Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five
      different kits in autoimmune thyroid diseases.
AB  - It is generally believed that the detection of thyroid peroxidase antibodies
      (TPOAb) is superior to that of thyroglobulin antibodies (TgAb) for the diagnosis
      of Hashimoto's thyroiditis. However, limited data are available on the comparison
      of TgAb and TPOAb prevalence as a diagnostic measurement for Hashimoto's
      thyroiditis using sensitive immunoassays. We herein used five different current
      immunoassay kits (A-E) to compare the prevalence of TgAb and TPOAb in Hashimoto's
      thyroiditis (n = 70), Graves' disease (n = 70), painless thyroiditis (n = 50),
      and healthy control subjects (n = 100). In patients with Hashimoto's thyroiditis,
      positive TgAb was significantly more frequent than positive TPOAb in kits A-D
      (mean +/- SD of the four kits: 98.6 +/- 1.7 vs 81.4 +/- 2.0%). In patients with
      Graves' disease, TgAb prevalence was almost equivalent to that of TPOAb in five
      kits. Patients with painless thyroiditis exhibited positive TgAb significantly
      more frequently than positive TPOAb in kits A-D (73.5 +/- 4.1 vs 33.0 +/- 3.4%).
      The prevalence of TgAb alone was significantly higher than that of TPOAb alone in
      both Hashimoto's thyroiditis and painless thyroiditis in kits A-D. In kit E, TgAb
      and TPOAb prevalence did not differ significantly for any disease, and TgAb
      distribution was different from other kits. In conclusion, the prevalence of TgAb
      was higher than that of TPOAb in patients with Hashimoto's thyroiditis and
      painless thyroiditis using commercially available kits. We suggest that TgAb
      immunoassay is the first choice of screening test for thyroid autoimmune
      abnormalities in Japan.

PMID- 28768937
TI  - Definitive surgical treatment of osteomalacia induced by skull base tumor and
      determination of the half-life of serum fibroblast growth factor 23.
AB  - Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome often
      associated with fibroblast growth factor 23 (FGF23)-producing tumors such as
      phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT)
      affecting the bone and soft tissue. We experienced a patient with progressive
      bone and muscle pain due to FGF23-related TIO. Venous sampling had strongly
      suggested the anterior skull base as a source of FGF23, which led to the
      discovery of a small tumor in the ethmoid sinus extending intracranially. Radical
      surgical resection confirmed the histological diagnosis of PMTMCT with FGF23
      immunopositivity and achieved durable tumor control with complete resolution of
      symptoms. We serially measured serum FGF23 level before, during and after surgery
      and analyzed the data to determine the half-life of FGF23. Serum FGF23 level
      sharply declined as early as 20 minutes after en bloc tumor resection and
      completely normalized after surgery. The half-life of FGF23 was calculated to be
      approximately 18.5 minutes using single phase exponential decay model as well as
      semilog transformation formula. Serial measurements of serum FGF23 level can
      potentially declare "complete" resection of a FGF23-producing tumor and total
      cure of TIO; in this regard, development of its intraoperative measurement would
      be helpful in the management of this endocrine tumor.

PMID- 28768938
TI  - A Novel Molecular Model of Plant Lectin-Induced Programmed Cell Death in Cancer.
AB  - Plant lectin, a class of highly diverse non-immune origin and carbohydrate
      binding proteins, has been reported to specially induce cancer cell through
      programmed cell death (PCD) pathways (apoptosis and/or autophagy), shedding
      lights on screening promising anti-cancer candidate agent for further therapeutic
      trials. However, the complicated molecular mechanisms by which plant lectins
      induced the programmed death of tumor cells, have not yet been fully clarified.
      Here, we summarized a novel model, based on vast amount of research, by which
      plant lectins eliminate various types of cancer cells via three major pathways,
      including a) direct ribosome inactivating, b) endocytosis-dependent mitochondrial
      dysfunction and c) sugar-containing receptors binding. A better understanding of
      the role of plant lectins played and further elucidation of the strategies
      targeting PCD would provide a new clue for the applications and modifications of
      plant lectin as a potential anti-cancer agent from bench to clinic.

PMID- 28768939
TI  - Latent profile analysis of lifestyle characteristics and health risk behaviors
      among Koreans who have completed industrial accident care.
AB  - This study investigated the characteristics and health behavior profiles of 1,803
      workers who had experienced industrial accidents. Average weekly exercise days,
      average number of cigarettes smoked per day, average daily sleep duration, and
      number of days of alcohol consumption were selected to investigate health
      behavior profiles. Specifically, latent profile analysis was applied to identify
      the health behavior profiles of people who had completed industrial accident
      care; the latent classes were the health-conscious type (n=240), the potential
      risk type (n=850), and the high-risk type (n=713). Comparison of the health
      conscious and potential-risk types indicated that younger subjects, the employed,
      and those with lower social status and life satisfaction were more likely to be
      the potential-risk type. Comparison of the health-conscious and high-risk types
      revealed that males, younger subjects, the employed, those without chronic
      illnesses, and those with lower social status and life satisfaction were more
      likely to be the high-risk type. The results suggest that industrial accident
      victims who have completed accident care have different health behaviors and it
      is necessary to improve health promotion based on health type characteristics.

PMID- 28768940
TI  - Inhalation Exposure Method for Illegal Drugs.
AB  - We developed a new inhalation exposure method to evaluate effects of synthetic
      cannabimimetics that are being distributed as new, unregulated drugs in the Tokyo
      area. We selected the commercial product "SOUTOU" containing AB-CHMINACA and 5F
      AMB as the test drug and dried marshmallow (Althaea officinalis) leaves as the
      negative control. A half cigarette packed with dried marshmallow leaves or SOUTOU
      was ignited, then mainstream smoke from each was delivered to five mice in an
      exposure box. After the cigarettes were fully consumed, neurobehavioral
      observations and a catalepsy test were performed at 15, 30 and 60 min after
      exposure. The effluent air from the exposure box was poured into impingers
      containing acetonitrile (first impinger) and dimethyl sulfoxide (second
      impinger). The resulting solutions were analyzed to assess decomposition of the
      synthetic cannabimimetics. Mice exposed to SOUTOU smoke showed many excitement
      behaviors and some suppressive behaviors at 15, 30 and 60 min. These clearly
      included cannabimimetic specific pharmacological actions. Negative control mice
      also showed some suppressive behaviors at 15 min but these were attenuated at
      later times, nearly disappearing at 60 min. In addition, the behavioral effects
      observed in controls were less pronounced than those in SOUTOU exposed mice. The
      inhalation exposure method developed in our study would be effective for
      determining cannabinoid specific pharmacological effects of illegal drugs, as
      well as for assessing the presence of active compound(s) by comparing the test
      substance with a negative control.

PMID- 28768941
TI  - A Method for Decreasing the Amount of the Drug Remaining on the Surfaces of the
      Mortar and Pestle after Grinding Small Amount of Tablets.
AB  - The aim of the present study was to develop a method for grinding tablets with a
      mortar and pestle while reducing drug loss because grinding tablets is known to
      be associated with reductions in tablet weight and loss of the active drug. Seven
      kinds of tablets were subjected to grinding. The proportion (%) of the amount of
      the active drug in the powder remaining on the surfaces of the mortar and pestle
      relative to the total amount of the drug recovered (the recovery percent) was
      calculated. The recovery percent of the 7 kinds of tablets ranged from 17.2
      35.9%, and the tablets' recovery percent decreased as the tablet weight
      increased. When the grinding was performed with 1 g of lactose monohydrate or 1 g
      of D-mannitol moistened with water, the recovery percent of the tablets decreased
      to 2.6-9.9% and 3.8-9.9%, respectively. The effects of the weight of lactose
      monohydrate on the recovery percent of Allegra(r) 60 mg tablets were examined. It
      was found that at least 0.6 g of lactose monohydrate was required to have a
      sufficient effect on drug recovery. Therefore, additives that have stronger
      effects at lower amounts were sought. As a result, calcium monohydrogen phosphate
      was found to have the strongest effect on drug recovery. The addition of 0.4 g
      calcium monohydrogen phosphate resulted in the recovery percent of 5.1%, which
      was significantly lower than that of 15.0% observed after the addition of 0.4 g
      lactose monohydrate, and lower than the 6.8% of 1 g lactose monohydrate.

PMID- 28768942
TI  - Relationship between Hay Fever and Mineral Concentration in the Hair, Lifestyle
      or Aging.
AB  - It is important to ingest just proportions of minerals to prevent disease, but
      these minerals are also secreted into the hair. Meanwhile, the number of hay
      fever patients in Japan is increasing, causing an increase in national medical
      expenses. In this study, we investigated the relationship between hay fever and
      mineral concentrations in hair to obtain findings on the risk of developing
      pollen allergies. A questionnaire survey was conducted for 275 men and 977 women
      on their lifestyle habits and ten kinds of mineral concentrations present in
      their hair were measured with subsequent analysis using nominal logistic
      regression analysis. The results indicated that half the patients in each age
      group had hay fever, with no significant difference between hay fever and aging,
      exercise habits, sleep and dietary rhythms. On the other hand, there was a
      significant difference between hay fever and mineral concentrations in the hair,
      and in men with hay fever, iron (odds ratio: 0.55, p<0.05) was low, while in
      women calcium (odds ratio: 0.67, p<0.05), chromium (odds ratio: 0.46, p<0.001),
      cadmium (odds ratio: 0.68, p<0.01) were low and selenium (odds ratio: 1.78,
      p<0.01) was high. These results, suggest that measurements mineral concentrations
      in hair are indicators of hay fever risk.

PMID- 28768943
TI  - What the Desirable Collaboration between Care Workers in Nursing Homes and
      Phamacists Should Be: An Approach for Security and Safe Medication for Residents
      in Nursing Homes.
AB  - In our previous research, there was no collaboration between care workers and
      pharmacists, for the most part. As a result, it was discovered that in some
      cases, problems concerning medication of nursing home residents had not been
      resolved. To solve this issue, we brought together care workers and pharmacists
      for a workshop we conducted. We assigned 12 care workers with at least two years
      of experience and 12 pharmacists to four mixed groups and guided them in the
      management of in-home long-term medical care and conducted small group
      discussions (SGD) using the KJ method. In the pre-survey before the workshop, all
      12 care workers replied "yes" to having experienced "concerns over medication"
      and nine (75%) replied "no" to having experienced "discussions (consultations)
      with pharmacists regarding the medication of residents". As a result of the SGD,
      "information sharing among professionals" was revealed as a problem common to all
      groups. Furthermore, common countermeasures for this issue included communication
      notes and holding collaborative meetings. In the post-survey after the workshop,
      67% of the participants replied that their thoughts concerning countermeasures
      were "coherent", and everyone replied that their "awareness was increased". In a
      follow-up survey after the workshop, 82% of the participants replied that they
      were using some form of what they had learned and discovered in the workshop in
      their actual work.

PMID- 28768944
TI  - Establishing a Case-study Program for the Promotion of Home Medical Care of
      Pharmacists-Fusing Education and Clinical Support.

PMID- 28768945
TI  - Background on Establishing a Working Group to Create Home Clinical Cases for
      Education.
AB  - In Japan there are concerns that there will be a surge in social insurance costs
      such as medical and nursing care expenses as a result of the baby boom generation
      reaching the late stages of old age (75 years old and beyond) around 2025 ("The
      2025 Problem"). In 2012, the "Outline on Social Insurance and Tax Reform" was
      approved by the Japanese cabinet and government, including "construction of
      regional comprehensive care". To promote participation in home medical care by
      pharmacists, this article presents the roles demanded of pharmacists in regional
      comprehensive care from the standpoint of physicians, and the discussion of case
      studies bridging the gap from knowledge learned in lectures to practical
      applications. In the field of medical education, "The 2023 Problem", regarding
      standards of education on a global level, caused medical schools across Japan to
      scramble for curriculum reform, specifically in the demand for increased time
      spent in clinical training and the expansion of community-based medical
      education. The current state of community-based medical education will be
      reviewed. In light of these developments, "the working group to create home
      clinical cases for education" was developed by clinical pharmacists in the field
      and university faculty members at Daiichi University of Pharmacy.

PMID- 28768946
TI  - Present Conditions and Problems of Home Care Education in Pharmaceutical
      Education: Through the Activities of "the Working Group to Create Home Clinical
      Cases for Education".
AB  - In the pharmaceutical education model core curriculums revision, "basic qualities
      required as a pharmacist" are clearly shown, and "the method based on learning
      outcomes" has been adopted. One of the 10 qualities (No. 7) is "Practical ability
      of the health and medical care in the community". In the large item "F.
      Pharmaceutical clinical" of the model core curriculums, "participation in the
      home (visit) medical care and nursing care" is written in "participation in the
      health, medical care, and welfare of the community", and it is an important
      problem to offer opportunities of home medical care education at university. In
      our university, we launched a working group to create "home clinical cases for
      education" from the educational point of view to pharmacy students to learn home
      medical care, in collaboration with university faculty members and pharmacists,
      who are practitioners of home care. Through its working group activities, we
      would like to organize the present conditions and problems of home care education
      in pharmaceutical education and to examine the possibility of using "home
      clinical case studies" in home care education at university.

PMID- 28768947
TI  - Present Activities and Problems of Home Medical Care by Pharmacists.
AB  - The rapidly aging population in Japan led to the revision of the dispensing fees,
      with reviews of the system for added fees on prescriptions for home-bound
      patients by one-pharmacist pharmacies. However, given the current situation, it
      is difficult for pharmacies to be engaged in home care, so there are few small
      pharmacies that are willing to do so. This situation led to a decrease in the
      number of pharmacists who are experienced in home care. Pharmacists are
      requesting that practical training in home care be included in the Model Core
      Curriculum. It is difficult for all students to receive Sample Practical
      Training, so I joined a working group that created case studies that demonstrate
      simulated experiences of home care. I believe that case studies are an
      instructional tool that offers essential points for acquiring practical
      knowledge. Case studies can reduce the anxiety of inexperienced pharmacists to
      engage in home care, and I expect that this educational approach will contribute
      to the promotion of business related to home care for pharmacists.

PMID- 28768948
TI  - Roles and Educational Effects of Clinical Case Studies in Home Medical Care.
AB  - Due to the progression of aging in Japan, pharmacists need to participate in home
      medical care. To enable pharmacists with no previous experience to participate in
      home medical care of patients with various diseases in the home environment, it
      is necessary to adopt an approach of training them in advance. It is thought
      useful for such clinical training to include patient case studies, which may
      facilitate the training of pharmacists for home medical care through simulated
      experience. "The working group to create home clinical cases for education" was
      launched by a group of university faculty, who have educational knowledge, and
      trained pharmacists who work with the patients at home. The home care cases were
      compiled by the university faculty members and the home care practice
      pharmacists. Working pharmacists and students at pharmaceutical college studied
      the same case studies of home medical care, and their self-evaluations were
      compared. They showed that the students rated themselves higher than the
      pharmacists. One of the reasons was the systematic education of the case studies.
      The clinical case studies are a good educational tool to promote home care
      medicine in pharmacies and university pharmaceutical colleges.

PMID- 28768949
TI  - Design and Synthesis of Peroxisome Proliferator-activated Receptor (PPAR) Gamma
      Antagonists Based on the Principle of Operation of Nuclear Receptor I.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) antagonist is a
      molecular target to create drug for the treatment of not only type 2 diabetes and
      obesity, but also cancer. However, few rational drug design strategies and
      concepts are available. Here, we utilized the nuclear receptor helix12-folding
      inhibition hypothesis, in combination with structural biology data of our
      PPARgamma agonist (5) complexed with the PPARgamma ligand-binding domain. We
      found a potent phenylalkynyl amide-type PPARgamma antagonist 18i, based on
      pinpoint structural modification of the acidic head part of 5. Although 18i
      exhibited potent PPARgamma antagonistic activity, it retained very weak, but
      distinct PPARgamma agonistic activity. We then modified the distal benzene ring
      of 18i, to delete the residual PPARgamma agonistic activity. Introduction of a
      chlorine atom at the 2-position of the distal benzene ring afforded 18p, which
      exhibited potent, PPARgamma-selective antagonistic activity without any
      detectable PPARgamma agonistic activity. We realized that 18p stabilized the
      corepressor-PPARgamma complex and suppressed basal PPARgamma activity. This
      compound showed potent anti-adipogenesis activity at the cellular level.

PMID- 28768950
TI  - Investigation of Oral Preparation That Is Expected to Improve Medication
      Administration: Preparation and Evaluation of Oral Gelling Tablet Using Sodium
      Alginate.
AB  - We investigated the preparation of a gelling tablet that swells and forms a gel
      upon absorbing water, and hence would be easy for patients to swallow. We
      prepared naked tablets and compressed coated tablets by the direct tableting or
      wet granule-compression methods, using the commonly prescribed drug acetaminophen
      (AA) and sodium alginate (AG) as a thickening agent. The tablets quickly absorbed
      water, had favorable gelling properties, low adhesiveness, appropriate drug
      dissolution profile, and at the same time, were easy to swallow. In the case of
      naked tablets, water absorption increased upon granulation, but gelling of AG
      interfere when AA and AG were present together. There was no change in the
      adhesiveness, and more than 30 min were required to achieve a 25% dissolution
      ratio. Compressed coated tablets that were made with AA in the inner layer and
      granulated AG in the outer layer showed improved dissolution behavior, it was
      about 90% dissolution ratio in 30 min, owing to the water absorption property of
      AG, and decreased adhesiveness. In this case, there was a difference in the outer
      layer thickness. As the outer layer amount increased, dissolution slowed, but it
      did not depend on the compression pressure. Our gelling tablet can be prepared by
      using AA (main drug) in the inner layer and an appropriate thickness of
      granulated AG in the outer layer of compressed coated tablets.

PMID- 28768951
TI  - Characterization and Evaluation of Skin Permeation of Tocopheryl Phosphoric Acid
      loaded Phospholipid Nanoparticles.
AB  - Tocopheryl phosphoric acid (TPA, a hydrophilic vitamin E derivative) loaded
      liposome and glycerin containing phospholipid nanoparticles (GPLNP) were prepared
      using the film rehydration and extrusion method. Nanoparticle formulations were
      evaluated for size, zeta potential, and in vitro permeation across hairless mouse
      skin, and 31P NMR spectral analysis was performed. The prepared formulations were
      stable for 2 weeks, and their mean nanoparticle size varied between 90 and 140
      nm. Although glycerin did not affect the particle size of the empty (no TPA)
      system, TPA-loading resulted in the reduction of particle size and conferred a
      negative charge. The 31P NMR spectral analysis showed that the presence of
      glycerin in the formulation changed the nanoparticle structure from a bilayer to
      a nonbilayer. Moreover, it was suggested that TPA molecules interacted with
      phospholipid by entrapping nanoparticles in the formulations. TPA did not
      permeate across the hairless mouse skin after 48 h. However, the TPA
      concentration in the hairless mouse skin after permeation study increased in the
      nanoparticle systems and the 30% GPLNP formulation was the best formulation for
      the accelerated TPA permeation in the hairless mouse skin. These results
      demonstrate that 30% GPLNP improved TPA permeation in the hairless mouse skin
      model. And it was strongly suggested that glycerin has an important role for
      changing the structure of nanoparticles and enhancing the skin permeation of TPA.

PMID- 28768952
TI  - Evaluation of an Evidence-based Medicine Educational Program for Pharmacists and
      Pharmacy Students.
AB  - This study evaluated the effect of an evidence-based medicine (EBM) educational
      program on EBM-related knowledge and skills of pharmacists and pharmacy students.
      Our preliminary educational program included the following four sessions: 1) ice
      breaker, 2) formulation of answerable clinical questions from virtual clinical
      scenario using the PICO criteria, 3) critical appraisal of the literature using a
      checklist, and 4) critical appraisal of the results and integrating the evidence
      with experience and patients values. Change in knowledge and skills related to
      EBM were evaluated using pre- and post-seminar 4-point scale questionnaires
      comprising of 14 questions. A total of 23 pharmacists, 1 care manager, and 5
      pharmacy students participated in our EBM educational seminar. Knowledge and
      skills related to several variables improved significantly post-seminar (pre
      seminar 2.80 versus 3.26 post-seminar; p<0.001). Specifically, the skills of
      formulating answerable clinical questions from virtual clinical scenario and
      critical appraisal of the literature using a checklist improved. Our findings
      suggested that EBM educational program using problem-based learning was effective
      in improving EBM-related knowledge and skills of pharmacists and pharmacy
      students.

PMID- 28768953
TI  - Effects of Tramadol Coadministration on Prothrombin Time-International Normalized
      Ratio in Patients Receiving Warfarin.
AB  - Several case studies have reported a possible drug interaction between warfarin
      and tramadol where tramadol coadministration enhanced the antithrombotic effects
      of warfarin. To assess this drug interaction, changes in prothrombin time
      international normalized ratio (PT-INR) before and after tramadol
      coadministration were investigated in patients receiving warfarin. For this
      study, we examined 54 patients (male/female: 22/32, 68.4+/-12.7 years) who were
      being treated with warfarin for deep vein thrombosis, atrial fibrillation,
      arteriosclerosis obliterans, congestive heart failure, and other vascular
      diseases. Significant increases in PT-INR were observed 9.5 (1-118) d after
      coadministration of tramadol (1.81+/-0.56 vs. 2.47+/-1.10, p<0.01). Twenty-eight
      patients (PT-INR increased group) with PT-INR elevation of greater than 0.5 or
      dose reduction of warfarin after coadministration of tramadol were compared with
      other groups of patients to find drug interaction risk factors. Logistic
      regression analysis revealed that lower levels of albumin (3.5 g/dL or less)
      [odds ratio (OR) 22.1; 95%CI 2.9-169.9]; lower eGFR (50 mL/min or less) (OR 7.7;
      95%CI 1.4-42.0); and PT-INR before tramadol coadministration (OR 38.2; 95%CI 3.7
      397.6) were characteristic of the PT-INR increased group. These results suggest
      that tramadol coadministration enhanced the antithrombotic effects of warfarin in
      patients with higher PT-INR, lower albumin levels and decreased renal function as
      the risk factors for this drug interaction.

PMID- 28768955
TI  - Special Issue: Symposium on the Chemistry of Terpenes, Essential Oils and
      Aromatics (TEAC).

PMID- 28768954
TI  - MiR-29a and miR-652 Attenuate Liver Fibrosis by Inhibiting the Differentiation of
      CD4+ T Cells.
AB  - BACKGROUND: Liver fibrosis is the response of liver diseases that puzzles
      patients. MiRNAs were involved in the regulating processes of liver fibrosis.
      This study aims to investigate the effects of ARRB1 mediated by miR-29a and miR
      652 on liver fibrosis and its possible mechanism. METHODS: Liver fibrosis of mice
      was induced by intraperitoneal injection of CCl4. Liver function was observed by
      the levels of alanine transaminase (ALT) and aspartate transaminase (AST). Flow
      cytometry was used to detect the percent of T helper17 (Th17). ELISA (Enzyme
      linked immunoassay) was used to detect the levels of Interleukin-17 (IL-17) and
      Interleukin-22 (IL-22). Real-time PCR was used to detect the expression of IL
      17A, IL-22, miR-29a, miR-652 and beta-Arrestin 1 Gene (ARRB1). Western blot was
      used to detect the protein expression of ARRB1. RESULTS: CCl4 supplementation
      significantly increased the level of ALT and AST, the percent of Th17, the level
      of IL-17A, IL-22, miR-29a and miR-652, but decreased ARRB1. Overexpression of miR
      29a/miR-652 prominently decreased Th17, IL-17A, IL-22 and ARRB1 in the normal
      CD4+ T cells. Both miR-29a and miR-652 targeted ARRB1 to regulate its expression.
      The effects of miR-29a/miR-652 overexpression on CD4+ T cells were reversed by
      ARRB1 overexpression. In vivo experiments demonstrated the protective role of miR
      29a/miR-652 overexpression on liver fibrosis. CONCLUSION: ARRB1 mediated by miR
      29a and miR-652 probably involved in the CD4+ T cells differentiation in patients
      with liver fibrosis, and functioned as a biomarker of fibrosis liver.Key words:
      liver fibrosis, miR-29a, miR-652, ARRB1, CD4+ T cells.

PMID- 28768956
TI  - Production of Valuable Lipophilic Compounds by Using Three Types of Interface
      Bioprocesses: Solid-Liquid Interface Bioreactor, Liquid-Liquid Interface
      Bioreactor, and Extractive Liquid-Surface Immobilization System.
AB  - Bioconversions such as enzymatic and microbial transformations are attractive
      alternatives to organic synthesis because of practical advantages such as
      resource conservation, energy efficiency, and environmentally harmonic
      properties. In addition, the production of secondary metabolites through
      microbial fermentation is also useful for manufacturing pharmaceuticals,
      agricultural chemicals, and aroma compounds. For microbial production of useful
      chemicals, the authors have developed three unique interfacial bioprocesses: a
      solid-liquid interface bioreactor (S/L-IBR), a liquid-liquid interface bioreactor
      (L/L-IBR), and an extractive liquid-surface immobilization (Ext-LSI) system. The
      S/L-IBR comprises a hydrophobic organic solvent (upper phase), a microbial film
      (middle phase), and a hydrophilic gel such as an agar plate (lower phase); the
      L/L-IBR and the Ext-LSI consist of a hydrophobic organic solvent (upper phase), a
      fungal mat with ballooned microspheres (middle phase), and a liquid medium (lower
      phase). All three systems have unique and practically important characteristics
      such as utilization of living cells, high concentration of lipophilic
      substrates/products in an organic phase, no requirement for aeration and
      agitation, efficient supply of oxygen, easy recovery of product, high regio- and
      stereoselectivity, and wide versatility. This paper reviews the principle,
      construction, characteristics, and application of these interfacial systems for
      producing lipophilic compounds such as useful aroma compounds, citronellol
      related compounds, beta-caryophyllene oxide, and 6-penty-alpha-pyrone.

PMID- 28768957
TI  - Regeneration of Used Frying Palm Oil with Coffee Silverskin (CS), CS Ash (CSA)
      and Nanoparticles of CS (NCS).
AB  - The present investigation aimed to evaluate the efficiency of coffee silverskin
      (CS), CS ash (CSA) and nanoparticles of CS (NCS) in regeneration the quality of
      used frying palm oil. The adsorbents were mixed individually with used frying
      palm oil at level 4% (w/v) for 60 min. The properties of CS, CSA and NCS
      adsorbents were studied using (SEM) scanning electron microscopy technique. Some
      of physico-chemical characteristics of used frying palm oil (UFPO) and UFPO
      treated with adsorbents were determined. The results showed that the CS ash
      particles composed of irregular spherical and semispherical grains with deep
      cavities. The size of particles of CS ash ranged in diameter from 1.1 to 1.7 um.
      The morphology of NCS consisted of cluster-type spherical nanoparticles and
      flakes. The particle size of NCS varies from 0.9 to 1.7 um. Purification
      treatments caused marked (p<0.05) increases in the quality parameters of treated
      oil compared to untreated oil. The treatment of UFPO with 4% of adsorbents caused
      significant reductions in the content of free fatty acids ranged from 51.2 to
      65.0%. The lowest level of peroxide (2.1 meq/kg) was recorded for UFPO treated
      with 4% of NCS. The highest reductions (72.8; 70.0%) in p-anisidine value were
      observed in UFPO treated with 4% of CSA and NCS, respectively. Treatment of UFPO
      with 4% of CS, CSA and NCS significantly lowered the polar content from 13.9% to
      6.3, 4.8 and 3.9%, respectively. The results also indicate that CSA and NCS have
      nearly the same adsorption efficiency in lowering polymer content of UFPO.
      Filtration treatment of UFPO with 4% of CS, CSA and NCS markedly lowered the
      viscosity and colour values of treated UFPO.

PMID- 28768958
TI  - Synthesis of Five and Six-Membered Heterocycles Using Activated Nitriles for
      Industrial Applications.
AB  - The aim of this study is a synthesis of new bioactive heterocyclic compounds
      incorporated fatty chain for use in different industrial applications.
      Cyanoacetamide derivative (2) was successfully transferred into five and six
      membered heterocyclic derivatives by the reaction with various chemical reagents.
      Addition number of moles of propylene oxide to these compounds gave nonionic
      surface-active agents having a good solubility, biodegradability and hence lowers
      the toxicity to human beings and becomes environmentally friendly. The
      antimicrobial and surface activities were investigated that showed the most of
      them have pronounced activity, which makes them suitable for diverse applications
      like the manufacturing of drugs, pesticides, emulsifiers, cosmetics, etc.

PMID- 28768959
TI  - Next generation sequencing-based mutation screening of 86 patients with
      idiopathic short stature.
AB  - Although mutations in ACAN, FGFR3, NPR2, and SHOX typically lead to skeletal
      dysplasia, and mutations in GHRHR, GH1, GHR, STAT5B, IGF1, IGFALS, and IGF1R
      usually underlie hormonal defects of the growth hormone (GH)-insulin-like growth
      factor 1 (IGF1) axis, such mutations have also been identified in patients with
      idiopathic short stature (ISS). Of these, SHOX abnormalities are known to account
      for a certain percentage of ISS cases, whereas the frequency of mutations in the
      other 10 genes in ISS cohorts remains unknown. Here, we performed next-generation
      sequencing-based mutation screening of the 10 genes in 86 unrelated Japanese ISS
      patients without SHOX abnormalities. We searched for rare protein-altering
      variants. The functional significance of the identified variants was assessed by
      in silico analyses. Consequently, we identified 18 heterozygous rare variants in
      19 patients, including four probable damaging variants in ACAN, six pathogenicity
      unknown variants in FGFR3, GHRHR, GHR, and IGFALS, and eight possible benign
      variants. Pathogenic variants in NPR2, GH1, and IGF1 were absent from our cohort.
      Unlike previously reported patients with ACAN mutations, our four patients with
      ACAN variants manifested non-specific short stature with age-appropriate or
      mildly delayed bone ages, and had parents of normal stature. These results
      indicate that ACAN mutations can underlie ISS without characteristic skeletal
      features, and that such mutations are possibly associated with de novo occurrence
      or low penetrance. In addition, our data imply that mutations in FGFR3, NPR2, and
      GH-IGF1 axis genes play only limited roles in the etiology of ISS.

PMID- 28768960
TI  - Circumferential Locations of Different Shapes of Short-segment Barrett's
      Esophagus.
AB  - Objective To clarify the relationship between the shape and circumferential
      location of non-circumferential short-segment Barrett's esophagus (SSBE). Methods
      We examined 3,788 subjects (2,497 males, 1,291 females; mean age 52.4 years) who
      underwent upper GI endoscopy as part of a detailed medical checkup. The presence
      of columnar-appearing mucosa >=10 mm long in the distal esophagus was diagnosed
      as BE and then divided into circumferential and non-circumferential localized
      types. Localized SSBE was further divided into round and sharp types based on the
      shape of the proximal margin. Results SSBE was endoscopically observed in 197
      subjects (5.2%). The numbers of patients with circumferential SSBE, round
      localized SSBE, and sharp localized SSBE were 38, 114 and 69, respectively. Round
      and sharp types of localized SSBE were simultaneously observed in 25 patients.
      Reflux esophagitis was more frequently observed in subjects with BE, regardless
      of type, in comparison to those without BE. Round localized SSBE was found mainly
      in the left posterior wall of the esophagus in a location similar to the main
      area of the esophageal cardiac glands. In contrast, sharp localized SSBE was
      observed mainly in the right anterior wall of the esophagus in a location similar
      to that of esophageal mucosal injury caused by mild type reflux esophagitis.
      Conclusion The location differs between round and sharp localized SSBE, possibly
      due to differences in the process of BE development.

PMID- 28768961
TI  - The Rate of Referral of Hepatitis Virus Carriers to Hepatologists and the Factors
      Contributing to Referral.
AB  - Objective The aims of the present study were to determine the proportions of
      hepatitis B surface antigen (HBsAg)-positive and anti-hepatitis C virus (HCV)
      positive patients, and identify the characteristics that influenced referral to a
      hepatologist. Methods The present study included patients who were positive for
      HBsAg (n=153) or anti-HCV (n=574); their viral status was tested by non
      hepatologists between January 2008 to December 2012. We performed a multivariate
      analysis to investigate the factors associated with the referral of patients to
      hepatologists. Results The rates of hepatitis B virus (HBV) and the percentage of
      suspected HCV carriers at the hospital were 1.4% and 3.5%, respectively. Among
      the 727 patients who were seropositive for HBV or HCV, 107 (14.7%) were referred
      to a hepatologist. A multivariate analysis to investigate the factors
      contributing to referral revealed that (i) an alanine aminotransferase (ALT)
      level of >30 IU/L [odds ratio (OR), 3.24; 95% confidence interval (CI), 2.10
      5.03; p<0.001]; (ii) undergoing testing at an internal medicine department (OR,
      2.79; 95% CI, 1.80-4.38; p<0.001); and (iii) HBsAg-positivity (OR, 2.22; 95% CI,
      1.35-3.61; p=0.002) were factors that significantly influenced referral.
      Conclusion Hepatologists must educate non-hepatologists, especially non
      internists, to promote the referral of hepatitis-virus carriers, especially HCV
      carriers, even in patients with ALT levels of <30 IU/L.

PMID- 28768962
TI  - A Modified Method for Examining the Walking Pattern and Pace of COPD Patients in
      a 6-min Walk Test Before and After the Inhalation of Procaterol.
AB  - Objective The 6-min walk test (6MWT) is a simple test that is used to examine the
      exercise tolerance and outcomes in patients with chronic obstructive pulmonary
      disease (COPD). Although the 6MWT is useful for assessing exercise tolerance, it
      is difficult to evaluate time-dependent parameters such as the walking pattern. A
      modified 6MWT has been devised to assess the walking pattern by calculating the
      number of steps per second (NSPS). This study was performed to investigate
      walking pattern of COPD patients in the modified 6MWT before and after a single
      inhalation of the short-acting beta2-agonist procaterol. Methods Nine male COPD
      patients participated in this study. The 6MWT was performed before and after the
      inhalation of procaterol hydrochloride. A digital video recording of the 6MWT was
      made. After the 6MWT, the number of steps walked by the subject in each 5-s
      period was counted manually with a hand counter while viewing the walking test on
      the video monitor. Results After the inhalation of procaterol, the 6-min walking
      distance increased significantly in comparison to baseline (p<0.01). The mean
      NSPS was also significantly increased after the inhalation of procaterol in
      comparison to baseline (p<0.01). The walking pattern was displayed on a graph of
      time versus NSPS, and the walking pace was shown by a graph of time versus
      cumulative steps. Conclusion The analysis of the COPD patients' walking test
      performance and their walking pattern and pace in the 6MWT may help to evaluate
      the effects of drug treatment.

PMID- 28768963
TI  - Clinical Features of Pulmonary Sarcoidosis Complicated by Lung Cancer.
AB  - Objective For lung cancer complicated with sarcoidosis, there are no exact
      features that indicate whether lymphadenopathy is metastatic. This makes the
      validity of surgery uncertain for clinicians. The aim of this study was to
      clarify the clinical features of pulmonary sarcoidosis complicated by lung
      cancer, especially from the viewpoint of evaluating lymphadenopathy. Methods We
      retrospectively reviewed medical records from 2004 to 2013 at our institution,
      and 18 patients who were diagnosed with sarcoidosis and lung cancer were thus
      found to be eligible. We investigated the relationship between the clinical and
      pathological findings of their swollen lymph nodes. Results Of 18 patients, 11
      conducted surgery, and the postoperative pathological evaluation of swollen lymph
      nodes was done in 8 of the patients. Postoperative N factor in all these patients
      was 0, even though lymphatic metastasis had been suspected preoperatively because
      of the unbalanced distribution of lymphadenopathy or the accumulation of
      fluorodeoxyglucose. Conclusion In patients with lung cancer complicated by
      sarcoidosis, the clinical assessment of the state of lymphadenopathy is difficult
      to make. However, as many of them tend to be benign, we suggest that surgical
      resection should be considered for a complete cure in the absence of any remote
      metastasis.

PMID- 28768964
TI  - The Risk Factors for the Wearing-off Phenomenon in Parkinson's Disease in Japan:
      A Cross-sectional, Multicenter Study.
AB  - Objective Parkinson's disease (PD) is a common, progressive, neurodegenerative
      disorder. With progression of PD, the wearing-off phenomenon occurs more
      frequently as a motor complication, decreasing the patient's quality of life. The
      aim of this study was to investigate the risk factors for the wearing-off
      phenomenon in Japanese PD patients. Methods All of the study participants were
      clinically diagnosed as having PD. Each patient was assessed for the wearing-off
      phenomenon based on the findings of clinical assessments and interviews that were
      conducted during a single visit. The risk factors for wearing-off were analyzed
      by univariate and multivariate logistic regression analyses. Results Wearing-off
      was observed in 101 of the 180 (56.1%) patients who were enrolled in this study.
      The multivariate logistic regression analysis revealed that the onset of PD at
      >=69 years of age (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.05
      0.88; p=0.032), female sex (OR, 6.49; 95% CI, 2.34-17.99; p<0.001), catechol-O
      methyltransferase (COMT) inhibitor treatment (OR, 19.59; 95% CI, 3.55-108.11;
      p<0.001) and a high daily levodopa dosage (>=600 mg/day) (OR, 7.69; 95% CI, 1.41
      41.84; p=0.018) were independent predictive factors for wearing-off in Japanese
      PD patients. Conclusion Age at the symptomatic disease onset, female sex, COMT
      inhibitor treatment, and a high daily levodopa dose were associated with the
      occurrence of wearing-off in Japanese PD patients. Physicians need to consider
      the risk factors and carefully choose medications for PD patients to postpone the
      occurrence of this phenomenon for as long as possible.

PMID- 28768965
TI  - Reactivation of Occult Hepatitis B Virus Infection 27 Months after the End of
      Chemotherapy Including Rituximab for Malignant Lymphoma.
AB  - A 68-year-old man with occult hepatitis B virus (HBV) infection was diagnosed
      with malignant lymphoma and achieved complete remission after treatment with a
      chemotherapy regimen including rituximab for 5 months. Entecavir (ETV) was also
      used during and after chemotherapy and was ended at 14 months after chemotherapy.
      However, reactivation of HBV was observed in blood tests, which showed not only
      elevation of HBV-DNA but also HBsAg and HBeAg, at 27 months after the end of
      chemotherapy. After restarting ETV, the HBV-DNA levels immediately subsided. In
      addition, anti-HBs became and remained positive at 31 months after chemotherapy.
      ETV was re-discontinued at 36 months after chemotherapy.

PMID- 28768966
TI  - Multiple Giant Coronary Artery Aneurysms.
AB  - A 74-year-old man was admitted to our hospital with chest pain and dyspnea
      associated with ST elevation in leads II, III and aVF. An echocardiogram showed
      an enlarged mass lesion measuring nearly 80 mm. Coronary angiography showed two
      giant coronary artery aneurysms (CAAs) in the right coronary artery (RCA). CAAs
      were also seen in the left main trunk and left anterior descending artery.
      Computed tomography showed the CAA in the RCA was ruptured into the right atrium.
      We therefore diagnosed this patient with multiple CAAs, myocardial infarction and
      coronary artery rupture. He underwent successful surgical excision and coronary
      bypass surgery.

PMID- 28768967
TI  - Dabigatran Therapy Resulting in the Resolution of Rivaroxaban-resistant Left
      Atrial Appendage Thrombi in Patients with Atrial Fibrillation.
AB  - Patients with persistent atrial fibrillation (AF) and a large left atrium are at
      a high risk for thromboembolisms. Recently, direct oral anticoagulants (DOACs)
      have mainly been used for the prevention of cardiac embolisms caused by AF.
      Transesophageal echocardiography (TEE) is performed in order to exclude any left
      atrial appendage (LAA) thrombi. We herein report two cases of persistent AF, both
      of which were treated with rivaroxaban for more than two years. Since TEE
      identified mobile LAA thrombi with this treatment, we switched from rivaroxaban
      to the direct thrombin inhibitor dabigatran. Dabigatran resolved the LAA thrombi
      that had been refractory to rivaroxaban.

PMID- 28768968
TI  - Isolated Adrenocorticotropic Hormone Deficiency Following Chronic Subdural
      Hematoma in an Elderly Man: Is There a Connection?
AB  - The delayed diagnosis of adrenal insufficiency is relatively common because its
      symptoms are non-specific. One of the causes of adrenal insufficiency is isolated
      adrenocorticotropic hormone deficiency (IAD), which is sometimes caused by
      traumatic brain injury. Indeed, severe head trauma is considered to contribute to
      the incidence of this disease. However, the relationship between milder head
      trauma-such as chronic subdural hematoma - and the occurrence of hormonal
      deficiency is uncertain. We herein report the case of a 79-year-old man with IAD
      who presented with leg edema and pain in his extremities following a recent
      history of chronic subdural hematoma.

PMID- 28768969
TI  - Werner Syndrome and Diabetes Mellitus Accompanied by Adrenal Cortex Cancer.
AB  - Werner syndrome is a rare genetic disease characterized by progeria, diabetes
      mellitus, cataracts and various types of malignancy. However, there are few
      reports showing adrenal cortex cancer in subjects with Werner syndrome. We herein
      report an extremely rare case of Werner syndrome accompanied by adrenal cortex
      cancer. Based on the data obtained from blood samples, computed tomography,
      magnetic resonance imaging and 131I adosterol scintigraphy, we diagnosed this
      subject with adrenal cortex cancer and Cushing's syndrome. Since the prognosis of
      adrenal cancer is very poor, we should be aware of the possibility of adrenal
      cancer occurring in subjects with Werner syndrome.

PMID- 28768970
TI  - Generalized Status Epilepticus in a Patient with Acute-onset Type 1 Diabetes
      Mellitus Associated with Severe Kidney Dysfunction: A Case Report and Literature
      Review.
AB  - A 65-year-old Japanese man with advanced chronic kidney disease (CKD) developed
      acute-onset type 1 diabetes mellitus (T1D) that was associated with severe acute
      kidney injury and was manifested by generalized tonic-clonic status epilepticus.
      His seizures resolved without recurrence after correcting the diabetic
      ketoacidosis. Although hyperglycemia is an important cause of acute symptomatic
      seizure (ASS), patients with ketotic hyperglycemia develop ASS less frequently.
      In this T1D case with CKD, severe hyperglycemia in conjunction with other
      metabolic insults, such as uremia, hyponatremia, and hypocalcemia, probably
      provoked his seizure despite the severe ketonemia.

PMID- 28768971
TI  - Acute Renal Failure with Severe Loin Pain and Patchy Renal Vasoconstriction in a
      Patient without Hypouricemia, Provoked by Epileptic Seizure.
AB  - A 26-year-old Japanese man without hypouricemia and with 3 previous episodes of
      seizures concurrent with acute kidney injury (AKI) was admitted due to an
      epileptic seizure, lower back pain and AKI. His creatinine kinase levels were
      slightly elevated. Patchy renal ischemia on contrast-enhanced computed tomography
      and persistent residual contrast medium was observed, consistent with acute renal
      failure with severe loin pain and patchy renal ischemia after anaerobic exercise
      (ALPE). Diffusion-weighted imaging (DWI) demonstrated signal changes in the
      corresponding area. ALPE should be considered a cause of AKI following seizures.
      We recommend DWI as an alternative diagnostic modality.

PMID- 28768972
TI  - Extranodal NK/T-cell Lymphoma, Nasal Type Accompanied by PR3-ANCA-associated
      Glomerulonephritis.
AB  - A 62-year-old man exhibiting nasal obstruction and glomerulonephritis with
      proteinase 3-antineutrophil cytoplasmic antibodies (PR3-ANCAs) was diagnosed with
      extranodal NK/T-cell lymphoma, nasal type (ENKL) with infiltration of neutrophils
      with apoptosis. Chemoradiotherapy reduced the tumor, improved the renal function,
      and decreased the PR3-ANCA levels. ANCA-positivity is observed in
      immunoinsufficient diseases, in which neutrophils lead to apoptosis and
      translocate intracellular granules, such as PR3, to the cell surface, triggering
      the production of ANCAs. In our case, the PR3-ANCA production was derived from
      the expression of PR3 on the cell surface of apoptotic neutrophils. This is the
      first report on ENKL describing the mechanism of ANCA development.

PMID- 28768973
TI  - Histological Transformation to Large Cell Neuroendocrine Carcinoma from Lung
      Adenocarcinoma Harboring an EGFR Mutation: An Autopsy Case Report.
AB  - We herein report a 58-year-old Japanese woman who survived 14 years after surgery
      for lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) exon
      19 deletion. She developed recurrence, for which she underwent multimodal
      therapy, including EGFR-tyrosine kinase inhibitor (TKI) administration. She
      ultimately died from a rapidly progressive right lung tumor that was resistant to
      EGFR-TKI. According to the autopsy findings, she had combined large-cell
      neuroendocrine carcinoma (LCNEC) and adenocarcinoma in the right lung, which
      retained an EGFR exon 19 deletion in both components. Therefore, the histological
      transformation to LCNEC can be a mechanism of acquired EGFR-TKI resistance.

PMID- 28768974
TI  - Platypnea-orthodeoxia Syndrome Induced by an Infected Giant Hepatic Cyst.
AB  - An 83-year-old man was admitted with a chief complaint of exacerbation of
      dyspnea. His blood oxygen saturation was 90% in the recumbent position despite
      oxygen therapy, and it dropped to less than 80% when the patient attempted to sit
      upright. A computed tomography scan revealed a giant hepatic cyst compressing the
      right atrium and the inferior vena cava. After percutaneous drainage, the oxygen
      saturation improved and did not change with alteration of the patient's positions
      from recumbent to sitting or standing. This case report describes a patient with
      the platypnea-orthodeoxia syndrome due to a giant hepatic cyst successfully
      managed by percutaneous drainage.

PMID- 28768975
TI  - Sudden Death in a Patient with Pulmonary Veno-occlusive Disease (PVOD) and Severe
      Pulmonary Hypertension.
AB  - A 58-year-old woman was referred to our hospital with a chief complaint of
      exertional dyspnea. Bronchoscopy failed to establish a diagnosis, and the patient
      subsequently died suddenly due to respiratory insufficiency because of advanced
      pulmonary hypertension (PH). The pathological diagnosis at autopsy was pulmonary
      veno-occlusive disease (PVOD). PVOD is difficult to diagnose antemortem and has a
      poor prognosis. Lung transplantation is the only curative treatment for PVOD.

PMID- 28768976
TI  - Occult Thyroid Follicular Carcinoma Diagnosed as Metastasis to the Chest Wall.
AB  - Chest wall tumors are relatively rare, and hematogenous metastasis to the chest
      wall is very rare. We herein describe a rare case of occult thyroid carcinoma as
      metastasis to the chest wall in an 80-year-old woman. The patient received
      detailed examinations of the chest wall tumor, and the results suggested that she
      had occult thyroid carcinoma. Surgery was then performed to remove all of her
      thyroid. As a result, she was diagnosed with follicular carcinoma of the thyroid.
      We report an extremely rare case of occult thyroid carcinoma diagnosed as
      hematogenous metastasis to the chest wall.

PMID- 28768977
TI  - The First Case of Pseudomonas aeruginosa Bacteremic Pneumonia in a Cancer Patient
      Receiving Pegfilgrastim.
AB  - A single dose of pegfilgrastim or the daily administration of colony-stimulating
      factors can be used to prevent febrile neutropenia. This may delay the detection
      of rapidly progressive infections among cancer patients undergoing chemotherapy.
      We report a case of Pseudomonas aeruginosa bacteremic pneumonia that occurred in
      a patient receiving pegfilgrastim.

PMID- 28768978
TI  - Primary CD30-positive Diffuse Large B-cell Lymphoma in the Superior Vena Cava.
AB  - Primary superior vena cava lymphoma originating from the endothelium of a large
      vein is very rare. A 70-year-old man was admitted to the hospital; computed
      tomography showed a tumor limited to the inside of the superior vena cava,
      completely occluding the vessel. A transjugular biopsy confirmed the diagnosis of
      diffuse large B-cell lymphoma, which was diffusely positive for CD30. Rituximab
      monotherapy followed by five courses of R-CHOP chemotherapy induced a complete
      remission. There was no recurrence after two years. The pathophysiology of
      lymphoma derived from large vessels may be different from intravascular large B
      cell lymphoma, which usually involves small vessels.

PMID- 28768979
TI  - Paraneoplastic Sarcoidosis in Multiple Myeloma.
AB  - Sarcoidosis predominantly affects the lungs, intrathoracic lymph nodes, and eyes;
      it less frequently affects the musculoskeletal system. We herein report a case of
      paraneoplastic sarcoidosis in a patient presenting with multiple myeloma. The
      patient developed ocular sarcoidosis and showed an increased 18F
      fluorodeoxyglucose uptake in the mediastinal lymph nodes and vertebral column. A
      lymph node specimen showed the histological features of sarcoidosis, while an
      examination of the vertebral tumor revealed myeloma. Although the simultaneous
      occurrence of sarcoidosis and myeloma is extremely rare, our case indicates the
      importance of exculing any underlying malignancies before establishing a
      diagnosis of skeletal sarcoidosis when bone lesions are observed at unusual
      sites.

PMID- 28768980
TI  - Thyrotoxicosis Presenting as Unilateral Drop Foot.
AB  - Neuromuscular disorders associated with hyperthyroidism have several variations
      in their clinical phenotype, such as ophthalmopathy, periodic paralysis, and
      thyrotoxic myopathy. We herein report an unusual case of thyrotoxic myopathy
      presenting as unilateral drop foot. Histopathological examinations of the left
      tibialis anterior muscle showed marked variation in the fiber size, mild
      inflammatory cell infiltration, and necrotic and regenerated muscle fibers with
      predominantly type 1 fiber atrophy. Medical treatment with propylthiouracil
      resulted in complete improvement of the left drop foot. This case expands the
      phenotype of thyrotoxicosis and suggests that thyrotoxicosis be considered as a
      possible cause of unilateral drop foot.

PMID- 28768981
TI  - Protein-losing Gastroenteropathy Related to Mixed Connective Tissue Disease: A
      Case Report of a Successful Outcome and Literature Review.
AB  - We herein report the case of a 44-year-old woman who developed protein-losing
      gastroenteropathy (PLGE) with hypoalbuminemia as the first manifestation of mixed
      connective tissue disease (MCTD). Albumin leakage from the stomach and intestinal
      tract was demonstrated by 99mTc-labeled human serum albumin scintigraphy. The
      patient's response to prednisolone therapy was insufficient; therefore,
      additional cyclosporin A (CsA) treatment was administered, and clinical remission
      was achieved. We concluded that although PLGE is a rare complication of MCTD, it
      may manifest as an initial clinical episode of MCTD. Furthermore, CsA can be a
      useful treatment option for refractory PLGE related to MCTD.

PMID- 28768982
TI  - Multicentric Reticulohistiocytosis with Dermatomyositis-like Eruptions.
AB  - A 68-year-old man presented with polyarthritis, proximal muscle weakness, and
      erythema of the face, arms, neck, and anterior chest that resembled the V-neck
      sign. Initially, dermatomyositis (DM) was considered because of the erythema,
      polyarthritis, and muscle weakness. He also had mediastinal and hilar
      lymphadenopathy on contrast-enhanced computed tomography. Unexpectedly, a biopsy
      of the forehead skin revealed numerous multinucleated giant cells. A biopsy of a
      solitary nodule on the dorsum of his right middle finger revealed similar
      multinucleated giant cells with ground-glass cytoplasm, leading to the diagnosis
      of multicentric reticulohistiocytosis (MRH). Although MRH is rare, it should be
      remembered that MRH can mimic DM.

PMID- 28768983
TI  - Longitudinally Extensive Transverse Myelitis and Optic Neuropathy Associated with
      Syphilitic Meningomyelitis and Human Immunodeficiency Virus Infection: A Case
      Report and Review of the Literature.
AB  - The incidence of co-infection with Treponema pallidum and human immunodeficiency
      virus (HIV) is increasing in developing and developed countries. The neurological
      complications of both infections occasionally occur simultaneously during a
      clinical course. We herein report the case of an HIV carrier with syphilitic
      meningomyelitis and subclinical optic neuropathy. The patient presumably had
      latent syphilis and slowly developed longitudinally extensive transverse myelitis
      (LETM). A cerebrospinal fluid examination confirmed the diagnosis of active
      neurosyphilis based on an elevated T. pallidum hemagglutination assay index. A
      change in the patient's immune status, possibly due to HIV, might have converted
      the syphilis from latent to active, leading to LETM of the spinal cord.

PMID- 28768984
TI  - Primary Pulmonary Meningioma Presenting as a Coin Lesion.

PMID- 28768985
TI  - Polycarbophil Calcium Lodged in the Bronchus.

PMID- 28768986
TI  - Coexistence of Pulmonary Aspergilloma and Allergic Bronchopulmonary
      Aspergillosis.

PMID- 28768987
TI  - Tramlines Emerging on a Lower Leg.

PMID- 28768988
TI  - Pan-spinal Epidural Abscess in a Diabetic Patient.

PMID- 28768989
TI  - The Diagnosis of Secondary Syphilis by Gram and Giemsa Staining.

PMID- 28768990
TI  - Adult Rubella in a Returned Traveler.

PMID- 28768991
TI  - Brain Images in Fatal Methanol Intoxication.

PMID- 28768993
TI  - Molecular Basis of Nucleobase Transport Systems in Mammals.
AB  - Nucleobases are water-soluble compounds that need specific transporters to cross
      biological membranes. Cumulative evidence based on studies using animal tissues
      and cells indicates that the carrier-mediated transport systems for purine and
      pyrimidine nucleobases can be classified into the following two types:
      concentrative transport systems that mediate nucleobase transport depending on
      the sodium ion concentration gradient; and other systems that mediate facilitated
      diffusion depending on the concentration gradient of the substrate. Recently,
      several molecular transporters that are involved in both transport systems have
      been identified. The function and activity of these transporters could be of
      pharmacological significance considering the roles that they play not only in
      nucleotide synthesis and metabolism but also in the pharmacokinetics and delivery
      of a variety of nucleobase analogues used in anticancer and antiviral drug
      therapy. The present review provides an overview of the recent advances in our
      understanding of the molecular basis of nucleobase transport systems, focusing on
      the transporters that mediate purine nucleobases, and discusses the involvement
      of intracellular metabolism in purine nucleobase transport and chemotherapy using
      ganciclovir.

PMID- 28768994
TI  - Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the
      Retinal Delivery of Neuroprotectants.
AB  - The retina is a tissue essential for vision, and the blood-retina barrier (BRB)
      helps to maintain an optimal microenvironment for the neural system in the
      retina. Recent findings concerning the BRB showed the involvement of transporters
      at the inner and outer BRB in drug and nutrient transport, suggesting their
      utility in the development of novel drug delivery systems to the retina. An in
      vitro-in vivo relationship study of permeability suggested the influx transport
      of verapamil, a cationic drug, across the BRB, and further in vivo and in vitro
      studies of cationic drugs, such as verapamil, propranolol and clonidine, revealed
      the involvement of carrier-mediated process in their influx transport at the BRB.
      Studies on substrate specificity in TR-iBRB2 cells, an in vitro model cell line
      of the inner BRB, suggests the involvement of novel organic cation transporter in
      the influx transport of cationic drugs at the inner BRB. Considering the
      neuroprotective effect previously reported for several cationic drugs, such as
      propranolol and clonidine, the study of cation transport at the BRB is widely
      expected to improve the treatment of retinal diseases, such as diabetic
      retinopathy and age-related macular degeneration.

PMID- 28768995
TI  - Physiological Roles of Carnitine/Organic Cation Transporter OCTN1/SLC22A4 in
      Neural Cells.
AB  - Dysfunction in neurotransmission mediated by neurotransmitters causes various
      neurological disorders. Therefore, receptors and reuptake transporters of
      neurotransmitters have been focused on as a therapeutic target in neurological
      disorders. These membrane proteins have high affinity for a specific
      neurotransmitter and are highly expressed on synaptic membranes. In contrast,
      xenobiotic transporters have relatively lower affinity for neurotransmitters but
      widely recognize various organic cations and/or anions and are also expressed in
      brain neurons. However, it has been largely unknown why such xenobiotic
      transporters are expressed in neurons that play a key role in signal
      transduction. We have therefore attempted to clarify the physiological roles of
      one such xenobiotic organic cation transporter (OCT) in neural cells with the aim
      of obtaining new insight into the treatment of neurological disorders.
      Carnitine/organic cation transporter OCTN1/SLC22A4 is functionally expressed in
      neurons and neural stem cells. In particular, OCTN1 is expressed at much higher
      levels compared with other OCTs in neural stem cells and positively regulates
      their differentiation into neurons. OCTN1 accepts the naturally occurring food
      derived antioxidant ergothioneine (ERGO) as a good in vivo substrate. Because
      ERGO is highly distributed into the brain after oral ingestion, OCTN1 may
      contribute to the alleviation of oxidative stress and promotion of neuronal
      differentiation via the uptake of ERGO in the brain, perhaps abating symptoms of
      neurological disorders. In this review, we introduce current topics on the
      physiological roles of OCTs with a focus on OCTN1 in neural cells and discuss its
      possible application to the treatment of neurological disorders.

PMID- 28768996
TI  - Functional Expression of Organic Ion Transporters in Astrocytes and Their
      Potential as a Drug Target in the Treatment of Central Nervous System Diseases.
AB  - It has become widely acknowledged that astrocytes play essential roles in
      maintaining physiological central nervous system (CNS) activities. Astrocytes
      fulfill their roles partly through the manipulation of their plasma membrane
      transporter functions, and therefore these transporters have been regarded as
      promising drug targets for various CNS diseases. A representative example is
      excitatory amino acid transporter 2 (EAAT2), which works as a critical regulator
      of excitatory signal transduction through its glutamate uptake activity at the
      tripartite synapse. Thus, enhancement of EAAT2 functionality is expected to
      accelerate glutamate clearance at synapses, which is a promising approach for the
      prevention of over-excitation of glutamate receptors. In addition to such well
      known astrocyte-specific transporters, cumulative evidence suggests that multi
      specific organic ion transporters (i.e., organic cation/anion transporters
      [OCTs/OATs], carnitine/organic cation transporters [OCTNs], and organic anion
      transporting polypeptides [OATPs]) are also functionally expressed in astrocytes.
      Even though identification and characterization of their
      physiological/pathophysiological roles in astrocytes are in the initial stage,
      the findings obtained so far indicate that OCT3 and plasma membrane monoamine
      transporter are significantly involved in the clearance of biogenic amine
      neurotransmitters in the synaptic cleft, and that OCTN2 and OATP1C1 provide a
      cellular entry gate for carnitine/acetyl-L-carnitine and thyroxine, respectively.
      Therefore, organic ion transporters, including those mentioned above, are
      expected to become emerging pharmacological targets for various CNS diseases.
      With such expectations in mind, this review will briefly summarize the functional
      expression of organic ion transporters in astrocytes.

PMID- 28768997
TI  - Loss of Stearoyl-CoA Desaturase-1 Activity Induced Leptin Resistance in Neuronal
      Cells.
AB  - The lack of response to leptin's actions in the brain, "leptin resistance," is
      one of the main causes of the pathogenesis of obesity. However, although high-fat
      diets affect sensitivity to leptin, the underlying mechanisms of leptin
      resistance are still an enigma. Here we examined the effect of excess saturated
      fatty acids (SFAs) on leptin signaling in human neuronal cells. Palmitate, the
      principle source of SFAs in diet, induced leptin resistance in a human
      neuroblastoma cell line stably transfected with the Ob-Rb leptin receptor (SH
      SY5Y-ObRb). We next investigated the function of stearoyl-CoA desaturase-1
      (SCD1), an enzyme which converts SFAs into monounsaturated fatty acids (MUFAs),
      on leptin-induced signaling. We found that reduction of SCD1 activity, through
      SCD1 inhibition and knockdown, impairs leptin-induced signal transducer and
      activator of transcription 3 (STAT3) phosphorylation in human neuronal cells. Our
      findings suggested that SCD1 plays a key role in the pathophysiology of leptin
      resistance in neuronal cells associated with obesity.

PMID- 28768998
TI  - Synthesis and Biological Evaluation of Novel Thioether Pleuromutilin Derivatives.
AB  - To develop new pleuromutilin derivatives as veterinary antibiotic medicines, we
      designed and synthesized a series of new thioether pleuromutilin derivatives
      possessing acylthiazolyl moiety based on previously designed derivatives. The
      antibacterial properties of the prepared pleuromutilin derivatives were assessed
      in vitro by the broth dilution method against five kinds of bacteria and the
      mycoplasma Mycoplasma gallisepticum (MG). All of the tested compounds displayed
      moderate to good antibacterial activity to methicillin-sensitive Staphylococcus
      aureus (MSSA), methicillin-sensitive Staphylococcus epidermidis (MSSE),
      methicillin-resistant S. aureus (MRSA), Streptococcus agalactiae (S. aga) and MG.
      However, the activity to Pyogeniccoccus (Pyogens) was generally poor. Compounds
      13i and l showed potent antibacterial activity against MSSE and MRSA which are
      better than that of valnemulin. The structural modification for pleuromutilin
      affected the antibacterial activity. Amino substituents in the benzene ring can
      effectively improve activity. Compared with the analogue 13a that possesses
      unsubstitution benzoyl group, the nitro, methoxy, hydroxy and dichloro
      substituent contributed little to antibacterial activity. Increasing a methylene
      between benzene moiety and carbonyl group decreased the bioactivity of
      derivative. The analogues that obtained by the reaction of amino acids and
      intermediate 9 showed moderate activity.

PMID- 28768999
TI  - Characterization of Membrane Integrity and Morphological Stability of Human
      Salivary Exosomes.
AB  - Exosomes are derived from various sources, including primary and cultured cell
      lines and body fluids. It is now evident that they are important for
      communication between cells. They have, therefore, been proposed as potential
      carriers to deliver drugs to specific sites. In this study, we examined stability
      of exosomes derived from human saliva. Exosomes were stored at 4 degrees C for up
      to 20 months and their membrane integrity assessed. Several exosomal markers,
      such as dipeptidyl peptidase IV (DPP IV; membrane marker) and programmed cell
      death 6-interacting protein (Alix, lumen marker), were retained intact after 20
      months storage at 4 degrees C. Moreover, intact exosomes could be isolated from
      whole saliva that had been stored at 4 degrees C. Membrane disruption with
      detergents such as Triton X-100 and Nonidet P-40 caused partial solubilization of
      DPP IV and release of Alix into the supernatant. In contrast, sodium dodecyl
      sulfate treatment caused a complete disruption of the membrane. In addition,
      membrane stability was maintained after freezing and thawing. These results
      indicated that human saliva-derived exosomes are stable, maintaining their
      membrane integrity over a long storage period.

PMID- 28769000
TI  - A Novel Bongkrekic Acid Analog-Mediated Modulation of the Size of Lipid Droplets:
      Evidence for the Appearance of Smaller Adipocytes.
AB  - Thiazolidinediones (TZDs) are known as peroxisome proliferator-activated receptor
      gamma (PPARgamma) activators, and are used in the treatment of diabetes. Although
      the usefulness of TZDs has been demonstrated, some of their side effects are
      becoming an obstacle to their clinical applicability; edema is known to be evoked
      by the "structural characteristics" of TZD, but not by the PPARgamma activation.
      Thus, novel therapeutic modalities (i.e., non-TZD-type PPARgamma activators)
      having different structures to those of TZDs are desired. We previously
      identified bongkrekic acid (BKA) as a PPARgamma activator using the human breast
      cancer MCF-7 cell line as a model system. In the present study, we newly
      synthesized BKA analogs and examined the usefulness of BKA and its analogs as
      PPARgamma activators in differentiated adipocyte cells. Among the chemicals
      investigated, one of the BKA analogs (BKA-#2) strongly stimulated PPARgamma and
      the differentiation of 3T3-L1 cells similar to pioglitazone, a positive control.
      Furthermore, BKA-#2 reduced the size of lipid droplets in the mature adipocyte
      cells. The possible modulation mechanism by BKA-#2 is discussed.

PMID- 28769001
TI  - Selected Physicochemical and Biological Properties of Ethyl Ascorbic Acid
      Compared to Ascorbic Acid.
AB  - The aim of the work was the evaluation of selected biological and
      physicochemical, applicative properties of ethylated ascorbic acid (AAE) compared
      to ascorbic acid (AA). Thermogravimetry (TG), differential thermogravimetry
      (DTG), and differential thermal analysis (DTA) were conducted, followed by the
      evaluation of AAE decomposition by the UV-Vis spectroscopic method including the
      influence of temperature and pH. Scavenging, antimicrobial activity and
      cytotoxicity against L929 fibroblasts were also performed. The difference in mass
      loss between AA and AAE was 30% via TG. DTA revealed characteristic exothermic
      and endothermic effects. The AAE solution was more thermally stable than AA. The
      calculated zero-order rate constants of free-radical scavenging kinetics for AAE
      were in the range of 4.9*10-3-1.35*10-2 s-1. The activation energy for the
      process was 11,2281 kJ/mol. AAE was active against Staphylococcus (S.) aureus and
      Enterococcus (E.) faecalis and acted stronger against Candida (C.) albicans than
      AA. The concentrations of AA >=2.5% were cytotoxic, whereas in the case of AAE, a
      10% concentration was considered cytotoxic. DTG enables the detailed
      differentiation between AA and AAE. AAE in aqueous solution is more stable
      compared to AA. The antioxidant activity of AAE is significant. However, the
      reaction with 2,2-diphenyl-1-picrylhydrazyl (DPPH) indicates prolonged activity
      compared to AA. Variability in the antimicrobial activity of AAE may find
      practical application in the pharmaceutical and cosmetic industries. The
      potential for applicative aims may be supported by the relatively low in vitro
      toxicity of AAE.

PMID- 28769002
TI  - Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of Luseogliflozin, a
      Sodium Glucose Co-transporter 2 Inhibitor, in Japanese Patients with Type 2
      Diabetes Mellitus.
AB  - Luseogliflozin is a selective sodium glucose co-transporter 2 (SGLT2) inhibitor
      that reduces hyperglycemia in type 2 diabetes mellitus (T2DM) by promoting
      urinary glucose excretion (UGE). A clinical pharmacology study conducted in
      Japanese patients with T2DM confirmed dose-dependency of UGE with once-daily
      administration of luseogliflozin; however, the reason for sustained UGE after
      plasma luseogliflozin decreased was unclear. To elucidate the effect of
      inhibition rate constants, Kon and Koff, and to explain the sustained UGE, a
      pharmacokinetic-pharmacodynamic (PK-PD) model was built based on the mechanisms
      of glucose filtration in the glomerulus and reabsorption in the renal proximal
      tubule of kidney as well as the kinetics of competitive inhibition of SGLT1/2 and
      inhibition rate constants of SGLT2, by using UGE and plasma glucose levels and
      luseogliflozin concentrations. This acquired population PK-PD model adequately
      described the sustained UGE and the estimated population means of the inhibition
      constant for SGLT2 (Ki2) and inhibition-rate constants for SGLT2 (Kon and Koff)
      were 0.31- and 3.6-fold lower or higher than the in vitro values. Because the
      dissociation half-time of luseogliflozin from SGLT2 calculated from Koff, 6.81 h,
      was consistent with the value in vitro, we considered that the sustained UGE
      could be explained by the long dissociation half-time. Moreover, by calculating
      the SGLT2 inhibition ratio using the model, we discuss other properties of the
      UGE time course after luseogliflozin administration.

PMID- 28769003
TI  - The Involvement of the Oxidative Stress in Murine Blue LED Light-Induced Retinal
      Damage Model.
AB  - The aim of study was to establish a mouse model of blue light emitting diode
      (LED) light-induced retinal damage and to evaluate the effects of the antioxidant
      N-acetylcysteine (NAC). Mice were exposed to 400 or 800 lx blue LED light for 2
      h, and were evaluated for retinal damage 5 d later by electroretinogram amplitude
      and outer nuclear layer (ONL) thickness. Additionally, we investigated the effect
      of blue LED light exposure on shorts-wave-sensitive opsin (S-opsin), and
      rhodopsin expression by immunohistochemistry. Blue LED light induced light
      intensity dependent retinal damage and led to collapse of S-opsin and altered
      rhodopsin localization from inner and outer segments to ONL. Conversely, NAC
      administered at 100 or 250 mg/kg intraperitoneally twice a day, before dark
      adaptation and before light exposure. NAC protected the blue LED light-induced
      retinal damage in a dose-dependent manner. Further, blue LED light-induced
      decreasing of S-opsin levels and altered rhodopsin localization, which were
      suppressed by NAC. We established a mouse model of blue LED light-induced retinal
      damage and these findings indicated that oxidative stress was partially involved
      in blue LED light-induced retinal damage.

PMID- 28769004
TI  - Pharmacokinetic/Pharmacodynamic Analysis for Doripenem Regimens in Intensive Care
      Unit Patient.
AB  - Doripenem (DRPM) is a broad-spectrum antibacterial agent often used as empirical
      therapy for critically ill patients, although there is a lack of studies
      validating the recommended dosage regimen for patients admitted to intensive care
      unit (ICU), based on pharmacokinetic (PK)/pharmacodynamic (PD) index. In this
      study, we estimated the free time above minimum inhibitory concentration (fT>MIC
      (%)) of DRPM using population PK analysis of 12 patients in ICU, and evaluated
      the validity of the dosage regimen stratified by creatinine clearance. Using a 2
      compartment population PK model reported previously, the mean total clearance or
      distribution volume of DRPM estimated by Bayesian estimation was significantly
      lower or higher than that of based on population PK model. The estimated fT>MIC
      (%) of the recommended standard (normal renal function: 0.5 g every 8 h,
      moderate: 0.25 g every 8 h, severe renal impairment: 0.25 g every 12 h) and
      higher doses (normal: 1.0 g every 8 h, moderate: 0.5 g every 8 h, severe: 0.25 g
      every 8 h) against MICs of 0.5, 1 and 2 ug/mL exceeded 40% in all patients. When
      stratified by creatinine clearance, the PK/PD breakpoints estimated by Monte
      Carlo simulation in three grades of renal function tended to be higher than the
      previously reported PK/PD breakpoints for patients with urinary tract infection,
      an infection of lesser severity than ICU patients. These results suggest that the
      dosage regimen stratified by renal function derived from Japanese package insert
      may be sufficient to achieve effective treatment in ICU patients.

PMID- 28769005
TI  - Oxymatrine Promotes S-Phase Arrest and Inhibits Cell Proliferation of Human
      Breast Cancer Cells in Vitro through Mitochondria-Mediated Apoptosis.
AB  - Breast cancer is one of the most lethal malignancies in the world. Oxymatrine is
      the major effective and toxic alkaloid component which is derived from the root
      of Sophora flavescens AIT, a traditional Chinese medicine which is widely
      distributed in Asia and the Pacific Islands. In the current research study, we
      investigated the effects and mechanisms of action of oxymatrine on breast cancer
      cells. We demonstrated that the viability and single cell proliferation
      capability of MCF-7 and MDA-MB-231, two breast cancer cell lines which are widely
      used in in vitro study, were significantly suppressed in a time- and
      concentration-dependent manner. Furthermore, the cell cycle of breast cancer
      cells treated with oxymatrine was arrested at the S-phase of the cell cycle.
      Oxymatrine also triggered apoptosis in breast cancer cells by modulating
      apoptosis-related proteins, such as cleaved Caspase-3, cleaved Caspase-9 and
      poly(ADP-ribose)polymerase (PARP). The remarkable reduction in the ratio of Bcl
      2/Bax was also observed in oxymatrine treated breast cancer cells. In conclusion,
      our research demonstrated that oxymatrine plays a critical role in suppressing
      carcinogenesis of breast cancer cells through cell cycle arrest and induction of
      mitochondria-mediated apoptosis, which suggests a promising application of this
      drug in breast cancer therapy.

PMID- 28769006
TI  - Mechanistic Study of Inhibitory Effects of Metformin and Atorvastatin in
      Combination on Prostate Cancer Cells in Vitro and in Vivo.
AB  - Metformin is a commonly used drug for the treatment of type II diabetes and
      atorvastatin is the most prescribed cholesterol-lowering statin. The present
      study investigated the effects and mechanisms of metformin and atorvastatin in
      combination on human prostate cancer cells cultured in vitro and grown as
      xenograft tumor in vivo. Metformin in combination with atorvastatin had stronger
      effects on growth inhibition and apoptosis in PC-3 cells than either drug alone.
      The combination also potently inhibited cell migration and the formation of
      tumorspheres. Metformin and atorvastatin in combination had a potent inhibitory
      effect on nuclear factor-kappaB (NF-kappaB) activity and caused strong decreases
      in the expression of its downstream anti-apoptotic gene Survivin. Moreover,
      strong decreases in the levels of phospho-Akt and phosphor-extracellular signal
      regulated kinase (Erk)1/2 were found in the cells treated with the combination.
      The in vivo study showed that treatment of severe combined immunodeficient (SCID)
      mice with metformin or atorvastatin alone resulted in moderate inhibition of
      tumor growth while the combination strongly inhibited the growth of the tumors.
      Results of the present study indicate the combination of metformin and
      atorvastatin may be an effective strategy for inhibiting the growth of prostate
      cancer and should be evaluated clinically.

PMID- 28769007
TI  - The Deletion of GPR40/FFAR1 Signaling Damages Maternal Care and Emotional
      Function in Female Mice.
AB  - The free fatty acid receptor 1 (GPR40/FFAR1) is activated by polyunsaturated
      fatty acids (PUFAs) such as docosahexaenoic acids (DHA). This receptor has been
      the focus of many studies regarding physiological functions of the central
      nervous system. PUFAs are essential for neuronal development and maintenance of
      neuronal function; thus, the decrease of PUFAs in the brain is closely related to
      the induction of psychiatric diseases associated with emotional disorder, such as
      anxiety, depression, and schizophrenia. However, details of the mechanisms remain
      unclear. In this study, we investigated changes of maternal and/or emotional
      behavior caused by a deficiency of GPR40/FFAR1 signaling. GPR40/FFAR1 deficient
      (FFAR1-/-) female mice exhibited impaired maternal care such as retrieving
      behaviors and an increased rate of neglect and infanticide when compared to wild
      type (WT) female mice. Furthermore, FFAR1-/- female mice showed increased time
      spent in the open arms in an elevated plus maze test, reduction of locomotor
      activity and social interaction behavior, and decreased sucrose intake, when
      compared to WT female mice. In conclusion, these findings suggest that PUFAs
      GPR40/FFAR1 signaling might function, at least in part, as a regulatory factor of
      emotional and maternal behavior in mice.

PMID- 28769008
TI  - Ketamine Alleviates Depressive-Like Behaviors via Down-Regulating Inflammatory
      Cytokines Induced by Chronic Restraint Stress in Mice.
AB  - The purpose of the present study was to investigate whether ketamine's rapid
      antidepressant effects were associated with its anti-inflammatory actions and to
      explore the underlying molecular mechanism. Depressive-like behaviors was induced
      in mice using chronic restraint stress (CRS) method. Anti-depressive effects of
      ketamine were evaluated by forced swimming tests (FST) and sucrose preference
      test (SPT). Subsequently, brain tissue was harvested to investigate inflammatory
      response in the hippocampus via investigating reactive microglia numbers, serum
      cytokines levels and the toll-like receptor type 4 (TLR4)/p38 mitogen-activated
      protein kinase (MAPK) pathway. CRS exposure caused depressive-like behaviors in
      mice, which was associated with increased pre-inflammatory cytokines (interleukin
      (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-6) levels, reactive
      microglia numbers and up-regulated regulatory molecules such as TLR4/p38 and P2X7
      receptor in hippocampus. Such neurobehavioral and biochemical abnormalities were
      normalized by ketamine treatment. CRS-induced depression-like behaviours are
      associated with activation of hippocampal inflammatory response, whereas down
      regulation of pro-inflammatory cytokines may contribute to ketamine's
      antidepressant effects in mice.

PMID- 28769009
TI  - Application of a Compact Magnetic Resonance Imaging System with 1.5 T Permanent
      Magnets to Visualize Release from and the Disintegration of Capsule Formulations
      in Vitro and in Vivo.
AB  - Although magnetic resonance imaging (MRI) has potential in assessments of
      formulations, few studies have been conducted because of the size and expense of
      the instrument. In the present study, the processes of in vitro and in vivo
      release in a gelatin capsule formulation model were visualized using a compact
      MRI system with 1.5 T permanent magnets, which is more convenient than the
      superconducting MRI systems typically used for clinical and experimental
      purposes. A Gd-chelate of diethylenetriamine-N,N,N',N",N"-pentaacetic acid, a
      contrast agent that markedly enhances proton signals via close contact with
      water, was incorporated into capsule formulations as a marker compound. In vitro
      experiments could clearly demonstrate the preparation-dependent differences in
      the release/disintegration of the formulations. In some preparations, the
      penetration of water into the formulation and generation of bubbles in the
      capsule were also observed prior to the disintegration of the formulation. When
      capsule formulations were orally administered to rats, the release of the marker
      into the stomach and its transit to the duodenum were visualized. These results
      strongly indicate that the compact MRI system is a powerful tool for
      pharmaceutical studies.

PMID- 28769010
TI  - Comparative Genomic Analysis MERS CoV Isolated from Humans and Camels with
      Special Reference to Virus Encoded Helicase.
AB  - Middle East Respiratory Syndrome Coronavirus (MERS CoV) is a new emerging viral
      disease characterized by high fatality rate. Understanding MERS CoV genetic
      aspects and codon usage pattern is important to understand MERS CoV survival,
      adaptation, evolution, resistance to innate immunity, and help in finding the
      unique aspects of the virus for future drug discovery experiments. In this work,
      we provide comprehensive analysis of 238 MERS CoV full genomes comprised of human
      (hMERS) and camel (cMERS) isolates of the virus. MERS CoV genome shaping seems to
      be under compositional and mutational bias, as revealed by preference of A/T over
      G/C nucleotides, preferred codons, nucleotides at the third position of codons
      (NT3s), relative synonymous codon usage, hydropathicity (Gravy), and aromaticity
      (Aromo) indices. Effective number of codons (ENc) analysis reveals a general
      slight codon usage bias. Codon adaptation index reveals incomplete adaptation to
      host environment. MERS CoV showed high ability to resist the innate immune
      response by showing lower CpG frequencies. Neutrality evolution analysis revealed
      a more significant role of mutation pressure in cMERS over hMERS. Correspondence
      analysis revealed that MERS CoV genomes have three genetic clusters, which were
      distinct in their codon usage, host, and geographic distribution. Additionally,
      virtual screening and binding experiments were able to identify three new virus
      encoded helicase binding compounds. These compounds can be used for further
      optimization of inhibitors.

PMID- 28769011
TI  - Chlorpheniramine Increases Paracellular Permeability to Marker Fluorescein
      Lucifer Yellow Mediated by Internalization of Occludin in Murine Colonic
      Epithelial Cells.
AB  - Ions, small molecules, and drugs are absorbed in the intestinal epithelium
      mediated by transcellular and paracellular pathways. The function of various
      transporters expressing in the apical and basolateral membranes of intestinal
      epithelial cells has been well characterized. In contrast, claudins and occludin,
      components of the tight junctions (TJs), determine the paracellular permeability
      to ions and low molecular weight compounds, but the properties for permeability
      has not been clarified in detail. In the present study, we examined the effects
      of anti-histamine drugs, chlorpheniramine and diphenhydramine, on transepithelial
      electrical resistance (TER) and permeability to lucifer yellow (LY), a marker of
      paracellular permeability, using murine colonic MCE301 cells. Chlorpheniramine
      significantly decreased the steady state of TER and increased permeability to LY,
      whereas the effects of diphenhydramine were not significant. The mRNAs of
      occludin and claudin-1-claudin-8 except for claudin-5 were expressed in MCE301
      cells. Both anti-histamine drugs did not change solubility of claudins to 0.5%
      Triton X-100 solution. In contrast, the detergent solubility and intracellular
      localization of occludin were significantly increased by chlorpheniramine. These
      results indicate that occludin is dissociated from the TJs by chlorpheniramine.
      Chlorpheniramine increased protein phosphatase-2A (PP-2A) activity, which was
      inhibited by cantharidin, a potent PP-2A inhibitor. Furthermore, the changes of
      TER, permeability to LY, and de-phosphorylation and tight junctional localization
      of occludin caused by chlorpheniramine were recovered by cantharidin. These
      results suggest that chlorpheniramine could increase paracellular permeability to
      low molecular weight compounds mediated by the activation of PP-2A and
      internalization of occludin in the colonic epithelial cells.

PMID- 28769012
TI  - In Vitro P-Glycoprotein-Mediated Transport of Tadalafil: A Comparison with
      Sildenafil.
AB  - Tadalafil and sildenafil are selective inhibitors of phosphodiesterase type 5,
      showing marked pharmacokinetic variability in patients with pulmonary arterial
      hypertension. It has been reported that sildenafil is a substrate for P
      glycoprotein (P-gp), but whether tadalafil is a substrate for P-gp remains to be
      determined. The objective of the present study was to elucidate whether tadalafil
      is a substrate for P-gp. Transcellular transport of sildenafil and tadalafil (5
      uM each) was examined using renal epithelial LLC-PK1 and P-gp-expressing LLC-GA5
      COL150 cell monolayers. The efflux ratio of the basal to apical (B to A)
      transport of sildenafil to the A to B transport after 120-min incubation in LLC
      GA5-COL150 cells (1.52) was significantly higher than that in LLC-PK1 cells
      (0.711). The efflux ratio of the B to A transport of tadalafil to the A to B
      transport after 120-min incubation in LLC-GA5-COL150 cells (10.4) was
      significantly higher than that in LLC-PK1 cells (1.23). In LLC-GA5-COL150 cell
      monolayers, the Vmax and Km values of sildenafil transport calculated from a
      modified Michaelis-Menten equation were 101+/-64 pmol/min/cm2 and 112+/-47 uM,
      respectively. On the other hand, those of tadalafil transport were 13.6+/-4.8
      pmol/min/cm2 and 22.7+/-9.3 uM, respectively. In the presence of a P-gp inhibitor
      (PSC833), the B to A transport of tadalafil was decreased by 28.6% in LLC-GA5
      COL150 cells, and the A to B transport of tadalafil was 6.59-fold greater than
      that in its absence. These results indicate that tadalafil is a substrate for P
      gp.

PMID- 28769013
TI  - Induction of the Histamine-Forming Enzyme Histidine Decarboxylase in Skeletal
      Muscles by Prolonged Muscular Work: Histological Demonstration and Mediation by
      Cytokines.
AB  - Recent studies suggest that histamine-a regulator of the microcirculation-may
      play important roles in exercise. We have shown that the histamine-forming enzyme
      histidine decarboxylase (HDC) is induced in skeletal muscles by prolonged
      muscular work (PMW). However, histological analysis of such HDC induction is
      lacking due to appropriate anti-HDC antibodies being unavailable. We also showed
      that the inflammatory cytokines interleukin (IL)-1 and tumor necrosis factor
      (TNF)-alpha can induce HDC, and that PMW increases both IL-1alpha and IL-1beta in
      skeletal muscles. Here, we examined the effects (a) of PMW on the histological
      evidence of HDC induction and (b) of IL-1beta and TNF-alpha on HDC activity in
      skeletal muscles. By immunostaining using a recently introduced commercial
      polyclonal anti-HDC antibody, we found that cells in the endomysium and around
      blood vessels, and also some muscle fibers themselves, became HDC-positive after
      PMW. After PMW, TNF-alpha, but not IL-1alpha or IL-1beta, was detected in the
      blood serum. The minimum intravenous dose of IL-1beta that would induce HDC
      activity was about 1/10 that of TNF-alpha, while in combination they
      synergistically augmented HDC activity. These results suggest that PMW induces
      HDC in skeletal muscles, including cells in the endomysium and around blood
      vessels, and also some muscle fibers themselves, and that IL-1beta and TNF-alpha
      may cooperatively mediate this induction.

PMID- 28769014
TI  - Inhibitory Activity of Catechin Metabolites Produced by Intestinal Microbiota on
      Proliferation of HeLa Cells.
AB  - Eleven kinds of catechin metabolites produced from (-)-epigallocatechin (EGC) and
      (-)-epigallocatechin gallate (EGCg) by intestinal microbiota were evaluated for
      inhibitory activity on the proliferation of HeLa cells, which are human cervical
      cancer cells. Among the catechin metabolites, 1-(3,4,5-trihydroxyphenyl)-3-(2,4,6
      trihydroxyphenyl)propan-2-ol (EGC-M2), 4-hydroxy-5-(3,4,5
      trihydroxyphenyl)valeric acid (EGC-M7), and 5-(3,4,5-trihydroxyphenyl)valeric
      acid (EGC-M9) were found to show inhibitory activity on HeLa cell proliferation
      as compared with control. The results suggested that three adjacent hydroxyl
      groups in the phenyl moiety may play an important role in the inhibitory
      activity. In addition, the inhibitory activity was also examined with four (-)
      epicatechin (EC) metabolites possessing two adjacent hydroxyl groups in the
      phenyl moiety. Only 5-(3,4-dihydroxyphenyl)valeric acid (EC-M9) showed inhibitory
      activity and therefore valeric acid moiety likely contributes to the inhibitory
      activity. EGC-M9 showed the strongest inhibitory activity with IC50 of 5.58 uM.
      Thus, in this study it was found for the first time that several catechin
      metabolites derived from EGC, EGCg, and EC inhibit the proliferation of cervical
      cancer cells.

PMID- 28769015
TI  - Ambient seismic wave field.
AB  - The ambient seismic wave field, also known as ambient noise, is excited by
      oceanic gravity waves primarily. This can be categorized as seismic hum (1-20
      mHz), primary microseisms (0.02-0.1 Hz), and secondary microseisms (0.1-1 Hz).
      Below 20 mHz, pressure fluctuations of ocean infragravity waves reach the abyssal
      floor. Topographic coupling between seismic waves and ocean infragravity waves at
      the abyssal floor can explain the observed shear traction sources. Below 5 mHz,
      atmospheric disturbances may also contribute to this excitation. Excitation of
      primary microseisms can be attributed to topographic coupling between ocean swell
      and seismic waves on subtle undulation of continental shelves. Excitation of
      secondary microseisms can be attributed to non-linear forcing by standing ocean
      swell at the sea surface in both pelagic and coastal regions. Recent developments
      in source location based on body-wave microseisms enable us to estimate forcing
      quantitatively. For a comprehensive understanding, we must consider the solid
      Earth, the ocean, and the atmosphere as a coupled system.

PMID- 28769016
TI  - Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase.
AB  - Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an anti-viral
      agent that selectively and potently inhibits the RNA-dependent RNA polymerase
      (RdRp) of RNA viruses. Favipiravir was discovered through screening chemical
      library for anti-viral activity against the influenza virus by Toyama Chemical
      Co., Ltd. Favipiravir undergoes an intracellular phosphoribosylation to be an
      active form, favipiravir-RTP (favipiravir ribofuranosyl-5'-triphosphate), which
      is recognized as a substrate by RdRp, and inhibits the RNA polymerase activity.
      Since the catalytic domain of RdRp is conserved among various types of RNA
      viruses, this mechanism of action underpins a broader spectrum of anti-viral
      activities of favipiravir. Favipiravir is effective against a wide range of types
      and subtypes of influenza viruses, including strains resistant to existing anti
      influenza drugs. Of note is that favipiravir shows anti-viral activities against
      other RNA viruses such as arenaviruses, bunyaviruses and filoviruses, all of
      which are known to cause fatal hemorrhagic fever. These unique anti-viral
      profiles will make favipiravir a potentially promising drug for specifically
      untreatable RNA viral infections.

PMID- 28769018
TI  - Fluorescence imaging of synapse dynamics in normal circuit maturation and in
      developmental disorders.
AB  - One of the most fundamental questions in neurobiology is how proper synaptic
      connections are established in the developing brain. Live-cell imaging of the
      synaptic structure and functional molecules can reveal the time course of synapse
      formation, molecular dynamics, and functional maturation. Using postsynaptic
      scaffolding proteins as a marker of synapse development, fluorescence time-lapse
      imaging revealed rapid formation of individual synapses that occurred within
      hours and their remodeling in culture preparations. In vivo two-photon excitation
      microscopy development enabled us to directly measure synapse turnover in living
      animals. In vivo synapse dynamics were suppressed in the adult rodent brain, but
      were maintained at a high level during the early postnatal period. This
      transition in synapse dynamics is biologically important and can be linked to the
      pathology of juvenile-onset psychiatric diseases. Indeed, the upregulation of
      synapse dynamics was observed in multiple mouse models of autism spectrum
      disorders. Fluorescence imaging of synapses provides new information regarding
      the physiology and pathology of neural circuit construction.

PMID- 28769017
TI  - TRP channels in oxygen physiology: distinctive functional properties and roles of
      TRPA1 in O2 sensing.
AB  - Transient Receptor Potential (TRP) proteins form cation channels characterized by
      a wide variety of activation triggers. Here, we overview a group of TRP channels
      that respond to reactive redox species to transduce physiological signals, with a
      focus on TRPA1 and its role in oxygen physiology. Our systematic evaluation of
      oxidation sensitivity using cysteine-selective reactive disulphides with
      different redox potentials reveals that TRPA1 has the highest sensitivity to
      oxidants/electrophiles among the TRP channels, which enables it to sense O2.
      Proline hydroxylation by O2-dependent hydroxylases also regulates the O2-sensing
      function by inhibiting TRPA1 in normoxia; TRPA1 is activated by hypoxia through
      relief from the inhibition and by hyperoxia through cysteine oxidation that
      overrides the inhibition. TRPA1 enhances neuronal discharges induced by hyperoxia
      and hypoxia in the vagus to underlie respiratory adaptation to changes in O2
      availability. This importance of TRPA1 in non-carotid body O2 sensors can be
      extended to the universal significance of redox-sensitive TRP channels in O2
      adaptation.

PMID- 28769019
TI  - Intrinsic ubiquitin E3 ligase activity of histone acetyltransferase Hbo1 for
      estrogen receptor alpha.
AB  - Estrogen receptors (ER) are important transcription factors to relay signals from
      estrogen and to regulate proliferation of some of breast cancers. The cycling of
      estrogen-induced DNA binding and ubiquitin-linked proteolysis of ER potentiates
      ER-mediated transcription. Indeed, several transcriptional coactivators for ER
      dependent transcription ubiquitinate ER. Histone acetyltransferase (HAT)
      Hbo1/KAT7/MYST2, involved in global histone acetylation, DNA replication,
      transcription, and cellular proliferation, promotes proteasome-dependent
      degradation of ERalpha through ubiquitination. However, molecular mechanism for
      ubiquitination of ERalpha by Hbo1 is unknown. Here we report the intrinsic
      ubiquitin E3 ligase activity of Hbo1 toward the ERalpha. The ligand, estradiol
      17beta, inhibited E3 ligase activity of Hbo1 for ERalpha in vitro, whereas
      hyperactive ERalpha mutants from metastatic breast cancers resistant to hormonal
      therapy, were better substrates for ERalpha ubiquitination by Hbo1. Hbo1 knock
      down caused increase in ERalpha expression. Hbo1 is another ERalpha coactivator
      that ubiquitinates ERalpha.

PMID- 28769020
TI  - Activation changes of the left inferior frontal gyrus for the factors of
      construction and scrambling in a sentence.
AB  - Our previous functional magnetic resonance imaging (fMRI) studies have indicated
      that the left dorsal inferior frontal gyrus (L. dF3op/F3t) and left lateral
      premotor cortex (L. LPMC) are crucial regions for syntactic processing among the
      syntax-related networks. In the present study, we further examined how
      activations in these regions were modified by the factors of construction and
      scrambling (object-initial type). Using various sentence types, we clarified
      three major points. First, we found that the main effects of construction and
      scrambling consistently activated the L. dF3op/F3t and L. LPMC. Secondly, the
      main effects of scrambling clearly localized activation in the L. dF3op/F3t and
      L. LPMC, indicating the more narrowed down processing of syntax. Thirdly, step
      wise percent signal changes were observed in the L. dF3op/F3t, demonstrating
      synergistic effects of construction and scrambling. These results demonstrate the
      abstract and intensive nature of syntactic processing carried out by these
      regions, i.e., the grammar center.

PMID- 28769021
TI  - Erratum to "Mechanisms of organelle division and inheritance and their
      implications regarding the origin of eukaryotic cells".

PMID- 28769022
TI  - Errata to "Rapid and coordinated processing of global motion images by local
      clusters of retinal ganglion cells".

PMID- 28769023
TI  - Isolation, Purification and Structural Characterization of Two Novel Water
      Soluble Polysaccharides from Anredera cordifolia.
AB  - Anredera cordifolia, a climber and member of the Basellaceae family, has long
      been a traditional medicine used for the treatment of hyperglycemia in China. Two
      water-soluble polysaccharides, ACP1-1 and ACP2-1, were isolated from A.
      cordifolia seeds by hot water extraction. The two fractions, ACP1-1 and ACP2-1
      with molecular weights of 46.78 kDa +/- 0.03 and 586.8 kDa +/- 0.05,
      respectively, were purified by chromatography. ACP1-1 contained mannose, glucose,
      galactose in a molar ratio of 1.08:4.65:1.75, whereas ACP2-1 contained arabinose,
      ribose, galactose, glucose, mannose in a molar ratio of 0.9:0.4:0.5:1.2:0.9.
      Based on methylation analysis, ultraviolet and Fourier transform-infrared
      spectroscopy, and periodate oxidation the main backbone chain of ACP1-1 contained
      (1->3,6)-galacturonopyranosyl residues interspersed with (1->4)-residues and (1
      >3)-mannopyranosyl residues. The main backbone chain of ACP2-1 contained (1->3)
      galacturonopyranosyl residues interspersed with (1->4)-glucopyranosyl residues.

PMID- 28769024
TI  - Nontargeted Metabolomic Analysis of Four Different Parts of Platycodon
      grandiflorum Grown in Northeast China.
AB  - Platycodonis radix is extensively used for treating cough, excessive phlegm, sore
      throat, bronchitis and asthma in the clinic. Meanwhile, the stems, leaves and
      seeds of Platycodon grandiflorum (PG) have some pharmaceutical activities such as
      anti-inflammation and anti-oxidation effects, etc. These effects must be caused
      by the different metabolites in various parts of herb. In order to profile the
      different parts of PG, the ultra-high performance liquid chromatography combined
      with quadrupole time-of- flight mass spectrometry (UPLC-QTOF-MSE) coupled with
      UNIFI platform and multivariate statistical analyses was used in this study.
      Consequently, for the constituent screening, 73, 42, 35, 44 compounds were
      characterized from the root, stem, leaf and seed, respectively. The stem, leaf
      and seed contain more flavonoids but few saponins that can be easily
      discriminated in the root. For the metabolomic analysis, 15, 5, 7, 11 robust
      biomarkers enabling the differentiation among root, stem, leaf and seed, were
      discovered. These biomarkers can be used for rapid identification of four
      different parts of PG grown in northeast China.

PMID- 28769025
TI  - Delayed Pacemaker Generator Pocket and Lead Primary Infection Due to Burkholderia
      Cepacia.
AB  - BACKGROUND Recently, the use of cardiac implantable electrophysiological devices
      (CIEDs) has increased. Advances in medical technology, an increasingly aging
      population, increases in clinical indications, and expanded medical insurance
      coverage for these devices have all contributed to this trend. Infection is
      considered to be one of the most serious complications of CIEDs and carries a
      significant risk of morbidity and mortality. Although infection with
      Staphylococcus sp. accounts for the majority of cases, other bacteria have been
      implicated as causative agents of infection of CIEDs. CASE REPORT We report the
      first case of primary pacemaker generator pocket and lead infection due to
      Burkholderia cepacia (B. cepacia) in the state of Qatar. To our knowledge, there
      have been few cases of CIED infection due to B. cepacia previously reported in
      the literature. CONCLUSIONS This case raises awareness of B. cepacia as a
      potential opportunistic pathogen in CIED infection. The more rare bacteria
      require culture on special media to provide an early diagnosis to enable proper
      antimicrobial therapy to commence. Adherence to infection control standards
      during CIED insertion would reduce infection from B. cepacia.

PMID- 28769026
TI  - Chemical Composition, Antioxidant, Anti-Inflammatory, and Antiproliferative
      Activities of the Plant Lebanese Crataegus Azarolus L.
AB  - BACKGROUND In the present study, phytochemical screening, antioxidant, anti
      inflammatory, and antiproliferative capacities of 3 extracts from leaves of
      Lebanese Crataegus azarolus L. were evaluated. MATERIAL AND METHODS Fresh leaves
      were dissolved in 3 different solvents: distilled water, ethanol, and methanol.
      The chemical composition was determined using high-performance liquid
      chromatography (HPLC) and the content of essential oil of this plant was examined
      by gas chromatography (GC) coupled with mass spectrometry (MS). The antioxidant
      potential was evaluated using DPPH radical scavenging and Fe2+ chelating activity
      assays. Anti-inflammatory effect was investigated by measuring the secreted
      amounts of the proinflammatory mediator PGE2 using ELISA technique, as well as by
      assaying the mRNA levels of the proinflammatory cytokines (IL-alpha, IL-beta, and
      Il-6), chemokines (CCL3 and CCL4) and inflammation-sensitive COX2 and iNOS
      enzymes using quantitative real-time PCR (qRT-PCR). The antiproliferative effect
      was evaluated using the XTT viability assay. RESULTS The obtained results show
      that alcohol (methanol and ethanol) extracts were rich in bioactive molecules
      with medical relevance and exerted substantial antioxidant, anti-inflammatory,
      and antiproliferative capacities. On the other hand, aqueous extract contained
      fewer chemical components and exhibited less therapeutic efficiency. CONCLUSIONS
      Our observations indicate that Crataegus azarolus L. could be used for treating
      diseases related to oxidative stress, inflammatory reactions, and uncontrolled
      cell growth.

PMID- 28769027
TI  - Synergistic Effect of Notch-3-Specific Inhibition and Paclitaxel in Non-Small
      Cell Lung Cancer (NSCLC) Cells Via Activation of The Intrinsic Apoptosis Pathway.
AB  - BACKGROUND Lung cancers are resistant to conventional chemotherapeutic
      interventions such as paclitaxel. Notch signaling is crucial in the
      chemoresistance of lung cancer cells. The Notch inhibitor gamma-secretase
      inhibitor (GSI) inhibits the Notch signaling pathway. MATERIAL AND METHODS Here,
      we evaluated how Notch-3 inhibition by GSI can enhance the sensitivity of lung
      cancer cells to paclitaxel. To study how Notch-3-specific inhibition affects non
      small cell lung cancer (NSCLC), we compared the cell viability, apoptosis, and
      colony formation of A549 and H1299 cells treated with Notch-3 siRNA and GSI.
      RESULTS The expression levels of Notch-3 or Notch intracellular domain 3 (NICD3)
      and apoptosis-related proteins were measured and compared between different
      groups. Notch-3 was significantly overexpressed in both cell lines, and Notch-3
      expression was elevated after paclitaxel treatment, indicating activation of the
      Notch signaling pathway. Inhibition of the Notch signaling pathway by GSI and
      Notch-3 siRNA reduced cell proliferation and induced apoptosis in A549 and H1299
      cells, thereby boosting sensitivity of the cell lines to paclitaxel. Concomitant
      treatment with paclitaxel and GSI or siRNA downregulated Bcl-2 expression and
      upregulated Bax expression levels. CONCLUSIONS These results indicate a
      synergistic effect of Notch-3-specific inhibition and paclitaxel through
      alteration of the intrinsic apoptosis pathway, which was involved in Notch-3
      induced chemoresistance in NSCLC cells, and GSI inhibited Notch-3-induced
      chemoresistance in a concentration-dependent manner. This approach that combines
      Notch-3-specific inhibition and paclitaxel would be likely to apply in NSCLC.

PMID- 28769028
TI  - Erratum: Catalyzed Synthesis of Zinc Clays by Prebiotic Central Metabolites.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 28769029
TI  - Loss of succinyl-CoA synthase ADP-forming beta subunit disrupts mtDNA stability
      and mitochondrial dynamics in neurons.
AB  - Succinyl Coenzyme A synthetase (SCS) is a key mitochondrial enzyme. Defected SCS
      ADP-forming beta subunit (SCS A-beta) is linked to lethal infantile Leigh or
      leigh-like syndrome. However, the impacts of SCS A-beta deficiency on
      mitochondria specifically in neurons have not yet been comprehensively
      investigated. Here, by down-regulating the expression levels of SCS A-beta in
      cultured mouse neurons, we have found that SCS A-beta deficiency induces severe
      mitochondrial dysfunction including lowered oxidative phosphorylation (OXPHOS)
      efficiency, increased mitochondrial superoxide production, and mtDNA depletion as
      well as aberrations of mitochondrial fusion and fission proteins, which
      eventually leads to neuronal stress. Our data also suggest that the deregulation
      of mitochondrial nucleoside diphosphate kinase (NDPK) together with defects in
      mitochondrial transcription factors including mitochondrial DNA pol gamma and
      Twinkle contribute to SCS A-beta deficiency-mediated mtDNA instability.
      Furthermore, we have found that SCS A-beta deficiency has detrimental influence
      on neuronal mitochondrial dynamics. Put together, the results have furnished our
      knowledge on the pathogenesis of SCS A-beta deficiency-related mitochondrial
      diseases and revealed the vital role of SCS A-beta in maintaining neuronal
      mitochondrial quality control and neuronal physiology.

PMID- 28769030
TI  - miR-30a acts as a tumor suppressor by double-targeting COX-2 and BCL9 in H.
      pylori gastric cancer models.
AB  - Helicobacter pylori (H. pylori) is one of the most important factors that affect
      the development of gastric cancer, and its mechanism remains un-elucidated. Our
      present study found that, miR-30a is crucial for regulating the growth and
      migration of H. pylori infected gastric cancer in vitro by targeting COX-2 and
      BCL9. In details, double-stranded miR-30a precursor produced two single-stranded
      and matured miRNAs including miR-30a-3p and miR-30a-5p, which played significant
      biological functions in two different manners. First, miR-30a-3p inhibited COX-2
      expression and regulated nuclear translocation of beta-catenin, and second, miR
      30a-5p targeted BCL9 to regulate TCF/LEF promoter activity followed by affecting
      beta-catenin downstream target gene expression. In vivo, miR-30a knockout mice
      were successfully achieved using CRISPR/Cas9 gene editing technology. Compared
      with H. pylori-infected wild-type mice, H. pylori-infected miR-30a knockout mice
      showed increased incidence of chronic gastritis, chronic atrophic gastritis,
      atypical hyperplasia, and other precancerous lesions or adenocarcinoma
      manifestations in the antral or gastric mucosa of mice, as well as regulation of
      genes closely associated with tumor development. Taken together, miR-30a acts as
      a tumor suppressor by double-targeting COX-2 and BCL9, and significantly affects
      the development of H. pylori-induced gastric cancer, shedding new light on the
      mechanisms underlying H. pylori-associated gastric cancer.

PMID- 28769031
TI  - Sex Specific Placental Accumulation and Behavioral Effects of Developmental
      Firemaster 550 Exposure in Wistar Rats.
AB  - Firemaster(r) 550 (FM 550) is a commercial flame retardant mixture of brominated
      and organophosphate compounds applied to polyurethane foam used in furniture and
      baby products. Due to widespread human exposure, and structural similarities with
      known endocrine disruptors, concerns have been raised regarding possible
      toxicity. We previously reported evidence of sex specific behavioral effects in
      rats resulting from developmental exposure. The present study expands upon this
      prior finding by testing for a greater range of behavioral effects, and measuring
      the accumulation of FM 550 compounds in placental tissue. Wistar rat dams were
      orally exposed to FM 550 during gestation (0, 300 or 1000 ug/day; GD 9 - 18) for
      placental measurements or perinatally (0, 100, 300 or 1000 ug/day; GD 9 - PND 21)
      to assess activity and anxiety-like behaviors. Placental accumulation was dose
      dependent, and in some cases sex specific, with the brominated components
      reaching the highest levels. Behavioral changes were predominantly associated
      with a loss or reversal of sex differences in activity and anxiety-like
      behaviors. These findings demonstrate that environmental chemicals may sex
      dependently accumulate in the placenta. That sex-biased exposure might translate
      to sex-specific adverse outcomes such as behavioral deficits is a possibility
      that merits further investigation.

PMID- 28769032
TI  - Vestigial-like 2 contributes to normal muscle fiber type distribution in mice.
AB  - Skeletal muscle is composed of heterogeneous populations of myofibers that are
      classified as slow- and fast-twitch fibers. The muscle fiber-type is regulated in
      a coordinated fashion by multiple genes, including transcriptional factors and
      microRNAs (miRNAs). However, players involved in this regulation are not fully
      elucidated. One of the members of the Vestigial-like factors, Vgll2, is thought
      to play a pivotal role in TEA domain (TEAD) transcription factor-mediated muscle
      specific gene expression because of its restricted expression in skeletal muscles
      of adult mice. Here, we generated Vgll2 null mice and investigated Vgll2 function
      in adult skeletal muscles. These mice presented an increased number of fast
      twitch type IIb fibers and exhibited a down-regulation of slow type I myosin
      heavy chain (MyHC) gene, Myh7, which resulted in exercise intolerance. In
      accordance with the decrease in Myh7, down-regulation of miR-208b, encoded within
      Myh7 gene and up-regulation of targets of miR-208b, Sox6, Sp3, and Purbeta, were
      observed in Vgll2 deficient mice. Moreover, we detected the physical interaction
      between Vgll2 and TEAD1/4 in neonatal skeletal muscles. These results suggest
      that Vgll2 may be both directly and indirectly involved in the programing of slow
      muscle fibers through the formation of the Vgll2-TEAD complex.

PMID- 28769033
TI  - Compositionally-distinct ultra-low velocity zones on Earth's core-mantle
      boundary.
AB  - The Earth's lowermost mantle large low velocity provinces are accompanied by
      small-scale ultralow velocity zones in localized regions on the core-mantle
      boundary. Large low velocity provinces are hypothesized to be caused by large
      scale compositional heterogeneity (i.e., thermochemical piles). The origin of
      ultralow velocity zones, however, remains elusive. Here we perform three
      dimensional geodynamical calculations to show that the current locations and
      shapes of ultralow velocity zones are related to their cause. We find that the
      hottest lowermost mantle regions are commonly located well within the interiors
      of thermochemical piles. In contrast, accumulations of ultradense compositionally
      distinct material occur as discontinuous patches along the margins of
      thermochemical piles and have asymmetrical cross-sectional shape. Furthermore,
      the lateral morphology of these patches provides insight into mantle flow
      directions and long-term stability. The global distribution and large variations
      of morphology of ultralow velocity zones validate a compositionally distinct
      origin for most ultralow velocity zones.Ultralow velocity zones are detected on
      the core-mantle boundary, but their origin is enigmatic. Here, the authors find
      that the global distribution and large variations of morphology of ultralow
      velocity zones are consistent with most having a compositionally-distinct origin.

PMID- 28769034
TI  - Prediction of thermal boundary resistance by the machine learning method.
AB  - Thermal boundary resistance (TBR) is a key property for the thermal management of
      high power micro- and opto-electronic devices and for the development of high
      efficiency thermal barrier coatings and thermoelectric materials. Prediction of
      TBR is important for guiding the discovery of interfaces with very low or very
      high TBR. In this study, we report the prediction of TBR by the machine learning
      method. We trained machine learning models using the collected experimental TBR
      data as training data and materials properties that might affect TBR as
      descriptors. We found that the machine learning models have much better
      predictive accuracy than the commonly used acoustic mismatch model and diffuse
      mismatch model. Among the trained models, the Gaussian process regression and the
      support vector regression models have better predictive accuracy. Also, by
      comparing the prediction results using different descriptor sets, we found that
      the film thickness is an important descriptor in the prediction of TBR. These
      results indicate that machine learning is an accurate and cost-effective method
      for the prediction of TBR.

PMID- 28769035
TI  - Spiraling pathways of global deep waters to the surface of the Southern Ocean.
AB  - Upwelling of global deep waters to the sea surface in the Southern Ocean closes
      the global overturning circulation and is fundamentally important for oceanic
      uptake of carbon and heat, nutrient resupply for sustaining oceanic biological
      production, and the melt rate of ice shelves. However, the exact pathways and
      role of topography in Southern Ocean upwelling remain largely unknown. Here we
      show detailed upwelling pathways in three dimensions, using hydrographic
      observations and particle tracking in high-resolution models. The analysis
      reveals that the northern-sourced deep waters enter the Antarctic Circumpolar
      Current via southward flow along the boundaries of the three ocean basins, before
      spiraling southeastward and upward through the Antarctic Circumpolar Current.
      Upwelling is greatly enhanced at five major topographic features, associated with
      vigorous mesoscale eddy activity. Deep water reaches the upper ocean
      predominantly south of the Antarctic Circumpolar Current, with a spatially
      nonuniform distribution. The timescale for half of the deep water to upwell from
      30 degrees  S to the mixed layer is ~60-90 years.Deep waters of the Atlantic,
      Pacific and Indian Oceans upwell in the Southern Oceanbut the exact pathways are
      not fully characterized. Here the authors present a three dimensional view
      showing a spiralling southward path, with enhanced upwelling by eddy-transport at
      topographic hotspots.

PMID- 28769036
TI  - Antiferromagnetic domain wall as spin wave polarizer and retarder.
AB  - As a collective quasiparticle excitation of the magnetic order in magnetic
      materials, spin wave, or magnon when quantized, can propagate in both conducting
      and insulating materials. Like the manipulation of its optical counterpart, the
      ability to manipulate spin wave polarization is not only important but also
      fundamental for magnonics. With only one type of magnetic lattice, ferromagnets
      can only accommodate the right-handed circularly polarized spin wave modes, which
      leaves no freedom for polarization manipulation. In contrast, antiferromagnets,
      with two opposite magnetic sublattices, have both left and right-circular
      polarizations, and all linear and elliptical polarizations. Here we demonstrate
      theoretically and confirm by micromagnetic simulations that, in the presence of
      Dzyaloshinskii-Moriya interaction, an antiferromagnetic domain wall acts
      naturally as a spin wave polarizer or a spin wave retarder (waveplate). Our
      findings provide extremely simple yet flexible routes toward magnonic information
      processing by harnessing the polarization degree of freedom of spin wave.Spin
      waves are promising candidates as carriers for energy-efficient information
      processing, but they have not yet been fully explored application wise. Here the
      authors theoretically demonstrate that antiferromagnetic domain walls are
      naturally spin wave polarizers and retarders, two key components of magnonic
      devices.

PMID- 28769037
TI  - Mechanism of biofilm-mediated stress resistance and lifespan extension in C.
      elegans.
AB  - Bacteria naturally form communities of cells known as biofilms. However the
      physiological roles of biofilms produced by non-pathogenic microbiota remain
      largely unknown. To assess the impact of a biofilm on host physiology we explored
      the effect of several non-pathogenic biofilm-forming bacteria on Caenorhabditis
      elegans. We show that biofilm formation by Bacillus subtilis, Lactobacillus
      rhamnosus and Pseudomonas fluorescens induces C. elegans stress resistance.
      Biofilm also protects against pathogenic infection and prolongs lifespan. Total
      mRNA analysis identified a set of host genes that are upregulated in response to
      biofilm formation by B. subtilis. We further demonstrate that mtl-1 is
      responsible for the biofilm-mediated increase in oxidative stress resistance and
      lifespan extension. Induction of mtl-1 and hsp-70 promotes biofilm-mediated
      thermotolerance. ilys-2 activity accounts for biofilm-mediated resistance to
      Pseudomonas aeruginosa killing. These results reveal the importance of non
      pathogenic biofilms for host physiology and provide a framework to study
      commensal biofilms in higher organisms.

PMID- 28769038
TI  - Increased mitochondrial fusion allows the survival of older animals in diverse C.
      elegans longevity pathways.
AB  - Mitochondria are dynamic organelles that undergo fusion and fission events.
      Mitochondrial dynamics are required for mitochondrial viability and for responses
      to changes in bioenergetic status. Here we describe an insulin-signaling and
      SCFLIN-23-regulated pathway that controls mitochondrial fusion in Caenorhabditis
      elegans by repressing the expression of the mitochondrial proteases SPG-7 and
      PPGN-1. This pathway is required for mitochondrial fusion in response to physical
      exertion, and for the associated extension in lifespan. We show that diverse
      longevity pathways exhibit increased levels of elongated mitochondria. The
      increased mitochondrial fusion is essential for longevity in the diverse
      longevity pathways, as inhibiting mitochondrial fusion reduces their lifespans to
      wild-type levels. Our results suggest that increased mitochondrial fusion is not
      a major driver of longevity, but rather is essential to allow the survival of
      older animals beyond their normal lifespan in diverse longevity
      pathways.Mitochondria can undergo shape changes as a result of fusion and fission
      events. Here the authors describe how insulin signalling regulates mitochondrial
      fusion in C. elegans, and show that mitochondrial fusion is necessary, but not
      sufficient, for longevity of worms with mutations that increase lifespan.

PMID- 28769039
TI  - Systematic Assessment of the Climate Sensitivity of Important Human and Domestic
      Animals Pathogens in Europe.
AB  - Climate change is expected to threaten human health and well-being via its
      effects on climate-sensitive infectious diseases, potentially changing their
      spatial distributions, affecting annual/seasonal cycles, or altering disease
      incidence and severity. Climate sensitivity of pathogens is a key indicator that
      diseases might respond to climate change, but the proportion of pathogens that is
      climate-sensitive, and their characteristics, are not known. The climate
      sensitivity of European human and domestic animal infectious pathogens, and the
      characteristics associated with sensitivity, were assessed systematically in
      terms of selection of pathogens and choice of literature reviewed. Sixty-three
      percent (N = 157) of pathogens were climate sensitive; 82% to primary drivers
      such as rainfall and temperature. Protozoa and helminths, vector-borne,
      foodborne, soilborne and waterborne transmission routes were associated with
      larger numbers of climate drivers. Zoonotic pathogens were more climate sensitive
      than human- or animal-only pathogens. Thirty-seven percent of disability-adjusted
      life-years arise from human infectious diseases that are sensitive to primary
      climate drivers. These results help prioritize surveillance for pathogens that
      may respond to climate change. Although this study identifies a high degree of
      climate sensitivity among important pathogens, their response to climate change
      will be dependent on the nature of their association with climate drivers and
      impacts of other drivers.

PMID- 28769040
TI  - Dimensionality Effects in FeGe2 Nanowires: Enhanced Anisotropic Magnetization and
      Anomalous Electrical Transport.
AB  - We report the synthesis of single-crystal iron germanium nanowires via chemical
      vapor deposition without the assistance of any catalysts. The assembly of single
      crystal FeGe2 nanowires with tetragonal C16 crystal structure shows anisotropic
      magnetic behavior along the radial direction or the growth axial direction, with
      both antiferromagnetic and ferromagnetic orders. Single FeGe2 nanowire devices
      were fabricated using e-beam lithography. Electronic transport measurement in
      these devices show two resistivity anomalies near 250 K and 200 K which are
      likely signatures of the two spin density wave states in FeGe2.

PMID- 28769041
TI  - Self-healing of damage inside metals triggered by electropulsing stimuli.
AB  - The microscopic defects that distributed randomly in metals are not only hard to
      detect, but also may inevitably cause catastrophic failure. Thus, autonomic
      probing and healing for damage inside metals continue to be a challenging. Here
      we show a novel approach for self-healing using electropulsing as a stimulus to
      trigger repairing of damaged metals. This is achieved via a process that through
      expelling absolutely currents, the microcrack causes them to be redistributed to
      form a concentrated and a diluted region around it, thereby inducing an extremely
      high temperature gradient and a large compressive stress, which drive material
      flow to close microcracks. Simultaneously, a large enough heat for bonding atoms
      was produced. That is, the microcrack as an empty cavity can be regarded as a
      special micro-device to shape a localized microscopic energy field, which in turn
      activates a healing process. The microstructure and mechanical property verified
      the extrinsic self-healing of a titanium alloy. The process is performed on a
      short timescale, is enable to detect automatically and act directly on the
      internal defects in metals, and to heal damage without any healing agent, long
      time heating as well as applied high pressure, offering unique advantages over
      conventional healing approaches.

PMID- 28769042
TI  - Local opposite orientation preferences in V1: fMRI sensitivity to fine-grained
      pattern information.
AB  - The orientation of a visual grating can be decoded from human primary visual
      cortex (V1) using functional magnetic resonance imaging (fMRI) at conventional
      resolutions (2-3 mm voxel width, 3T scanner). It is unclear to what extent this
      information originates from different spatial scales of neuronal selectivity,
      ranging from orientation columns to global areal maps. According to the global
      areal-map account, fMRI orientation decoding relies exclusively on fMRI voxels in
      V1 exhibiting a radial or vertical preference. Here we show, by contrast, that 2
      mm isotropic voxels in a small patch of V1 within a quarterfield representation
      exhibit reliable opposite selectivities. Sets of voxels with opposite
      selectivities are locally intermingled and each set can support orientation
      decoding. This indicates that global areal maps cannot fully account for
      orientation information in fMRI and demonstrates that fMRI also reflects fine
      grained patterns of neuronal selectivity.

PMID- 28769043
TI  - Common biological phenotypes characterize the acquisition of platinum-resistance
      in epithelial ovarian cancer cells.
AB  - Standard of care for Epithelial Ovarian Cancer (EOC) patients relies on platinum
      based therapy. However, acquired resistance to platinum occurs frequently and
      predicts poor prognosis. To understand the mechanisms underlying acquired
      platinum-resistance, we have generated and characterized three platinum-resistant
      isogenic EOC cell lines. Resistant cells showed 3-to 5- folds increase in
      platinum IC50. Cross-resistance to other chemotherapeutic agents commonly used in
      the treatment of EOC patients was variable and dependent on the cell line
      utilized. Gene expression profiling (GEP) of coding and non-coding RNAs failed to
      identify a common signature that could collectively explain the mechanism of
      resistance. However, we observed that all resistant cell lines displayed a
      decreased level of DNA platination and a faster repair of damaged DNA.
      Furthermore, all platinum resistant cell lines displayed a change in their
      morphology and a higher ability to grown on mesothelium. Overall, we have
      established and characterized three new models of platinum-resistant EOC cell
      lines that could be exploited to further dissect the molecular mechanisms
      underlying acquired resistance to platinum. Our work also suggests that GEP
      studies alone, at least when performed under basal culture condition, do not
      represent the optimal way to identify molecular alterations linked to DNA repair
      pathway defects.

PMID- 28769044
TI  - Intercellular Genetic Interaction Between Irf6 and Twist1 during Craniofacial
      Development.
AB  - Interferon Regulatory Factor 6 (IRF6) and TWIST1 are transcription factors
      necessary for craniofacial development. Human genetic studies showed that
      mutations in IRF6 lead to cleft lip and palate and mandibular abnormalities. In
      the mouse, we found that loss of Irf6 causes craniosynostosis and mandibular
      hypoplasia. Similarly, mutations in TWIST1 cause craniosynostosis, mandibular
      hypoplasia and cleft palate. Based on this phenotypic overlap, we asked if Irf6
      and Twist1 interact genetically during craniofacial formation. While single
      heterozygous mice are normal, double heterozygous embryos (Irf6 +/- ; Twist1 +/-
      ) can have severe mandibular hypoplasia that leads to agnathia and cleft palate
      at birth. Analysis of spatiotemporal expression showed that Irf6 and Twist1 are
      found in different cell types. Consistent with the intercellular interaction, we
      found reduced expression of Endothelin1 (EDN1) in mandible and transcription
      factors that are critical for mandibular patterning including DLX5, DLX6 and
      HAND2, were also reduced in mesenchymal cells. Treatment of mandibular explants
      with exogenous EDN1 peptides partially rescued abnormalities in Meckel's
      cartilage. In addition, partial rescue was observed when double heterozygous
      embryos also carried a null allele of p53. Considering that variants in IRF6 and
      TWIST1 contribute to human craniofacial defects, this gene-gene interaction may
      have implications on craniofacial disorders.

PMID- 28769045
TI  - Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine
      secretion by increasing regulatory T cells.
AB  - Arsenic is globally infamous for inducing immunosuppression associated with
      prevalence of opportunistic infection in exposed population, although the
      mechanism remains elusive. In this study, we investigate the effect of arsenic
      exposure on thymocyte lineage commitment and the involvement of regulatory T
      cells (Treg) in arsenic-induced immunosuppression. Male Balb/c mice were exposed
      to 0.038, 0.38 and 3.8 ppm sodium arsenite for 7, 15 and 30 days through oral
      gavage. Arsenic exposure promoted CD4 lineage commitment in a dose dependent
      manner supported by the expression of ThPOK in thymus. Arsenic also increased
      splenic CD4+ T cells and promoted their differentiation into Treg cells. In
      parallel,  arsenic exposure induced immunosuppression characterized by low
      cytokine secretion from splenocytes and increased susceptibility to Mycobacterium
      fortuitum (M. fortuitum) infection. Therefore, we linked arsenic-induced rise in
      Treg cells with suppressed Th1 and Th2 related cytokines, which has been reversed
      by inhibition of Treg cells in-vivo using wortmannin. Other parameters like body
      weight, kidney and liver function, histoanatomy of thymus and spleen as well as
      thymocyte and splenocytes viability were unaltered by arsenic exposure. Taken
      together our findings indicated that environmentally relevant dose of arsenic
      enhanced differentiation of Treg cells which in turn induce immunosuppression in
      experimental animals.

PMID- 28769046
TI  - Kaiso protects human umbilical vein endothelial cells against apoptosis by
      differentially regulating the expression of B-cell CLL/lymphoma 2 family members.
AB  - Endothelial cell injury can promote the development of various cardiovascular
      diseases, thus, fully understanding the mechanisms underlying the maintenance of
      vascular endothelial cell homoeostasis may help prevent and treat cardiovascular
      disease. Kaiso, a zinc finger and BTB domain containing transcription factor, is
      key to embryonic development and cancer, but how Kaiso interacts with vascular
      endothelium is not fully understood. We report that Kaiso has an anti-apoptotic
      function in human umbilical vein endothelial cells (HUVECs) and human
      microvascular endothelial cells (HMEC-1s). Overexpression of Kaiso significantly
      increased cell viability and inhibited hydrogen peroxide-induced apoptosis.
      Furthermore, Kaiso increased expression of B-cell CLL/lymphoma 2 (BCL2) and
      reduced expression of BCL2-associated X protein (BAX) and BCL2-interacting killer
      (BIK) by differentially regulating gene promoter activity. Methylated DNA and
      specific Kaiso binding site (KBS) contributed to gene regulatory activity of
      Kaiso. In addition, p120ctn functioned cooperatively in Kaiso-mediated
      transcriptional regulation.

PMID- 28769047
TI  - Effect of Niacin on Inflammation and Angiogenesis in a Murine Model of Ulcerative
      Colitis.
AB  - Butyrate and niacin are produced by gut microbiota, however butyrate has received
      most attention for its effects on colonic health. The present study aimed at
      exploring the effect of niacin on experimental colitis as well as throwing some
      light on the ability of niacin to modulate angiogenesis which plays a crucial
      role of in the pathogenesis of inflammatory bowel disease. Rats were given niacin
      for 2 weeks. On day 8, colitis was induced by intrarectal administration of
      iodoacetamide. Rats were sacrificed on day 15 and colonic damage was assessed
      macroscopically and histologically. Colonic myeloperoxidase (MPO), tumour
      necrosis factor (TNF)-alpha, interleukin (IL)-10, vascular endothelial growth
      factor (VEGF), angiostatin and endostatin levels were determined. Niacin
      attenuated the severity of colitis as demonstrated by a decrease in weight loss,
      colonic wet weight and MPO activity. Iodoacetamide-induced rise in the colonic
      levels of TNF-alpha, VEGF, angiostatin and endostatin was reversed by niacin.
      Moreover, niacin normalized IL-10 level in colon. Mepenzolate bromide, a GPR109A
      receptor blocker, abolished the beneficial effects of niacin on body weight,
      colon wet weight as well as colonic levels of MPO and VEGF. Therefore, niacin was
      effective against iodoacetamide-induced colitis through ameliorating pathologic
      angiogenesis and inflammatory changes in a GPR109A-dependent manner.

PMID- 28769048
TI  - In vivo monitoring of the recruitment and activation of AP-1 by Arf1.
AB  - AP-1 is a clathrin adaptor recruited to the trans-Golgi Network where it can
      interact with specific signals found in the cytosolic tail of cargo proteins to
      incorporate them into clathrin-coated vesicles for trafficking. The small G
      protein Arf1 regulates the spatiotemporal recruitment of AP-1 and also drives a
      conformational change favoring an interaction with cargo proteins. A recent
      crystal structure and in vitro experiments highlighted potential residues
      mediating the AP-1/Arf1 interaction and the unlocking of the complex. We have
      used bioluminescence resonance energy transfer (BRET) to study the Arf1/AP-1
      interaction and AP-1 conformational changes in vivo. We identified novel residues
      required for this interaction in addition to those predicted in the crystal
      structure. We also studied the conformational changes in AP-1 driven by Arf1 in
      live cells and found that opening of the complex is prerequisite for
      oligomerization. Using Arf1 knockout cells generated by CRISPR/Cas9, we
      demonstrated that residue 172 in Arf1 is necessary for AP-1 activation and is
      required for the efficient sorting of the lysosomal protein prosaposin. We have
      used BRET to study the in vivo activation of AP-1. The advantages of BRET include
      expressing full-length proteins in their native environment that have been fully
      post-translationally modified.

PMID- 28769050
TI  - Persistent current in 2D topological superconductors.
AB  - A junction between two boundaries of a topological superconductor (TSC), mediated
      by localized edge modes of Majorana fermions, is investigated. The tunneling of
      fermions across the junction depends on the magnetic flux. It breaks the time
      reversal symmetry at the boundary of the sample. The persistent current is
      determined by the emergence of Majorana edge modes. The structure of the edge
      modes depends on the magnitude of the tunneling amplitude across the junction. It
      is shown that there are two different regimes, which correspond to strong and
      weak tunneling of Majorana fermions, distinctive in the persistent current
      behavior. In a strong tunneling regime, the fermion parity of edge modes is not
      conserved and the persistent current is a 2pi-periodic function of the magnetic
      flux. When the tunneling is weak the chiral Majorana states, which are
      propagating along the edges have the same fermion parity. They form a 4pi-phase
      periodic persistent current along the boundaries. The regions in the space of
      parameters, which correspond to the emergence of 2pi- and of 4pi-harmonics, are
      numerically determined. The peculiarities in the persistent current behavior are
      studied.

PMID- 28769049
TI  - Dynamics of angiogenesis in ischemic areas of the infarcted heart.
AB  - Cardiomyocytes are susceptible to apoptosis caused by hypoxia during the acute
      and subacute phases of myocardial infarction (MI). Angiogenesis can reduce MI
      induced damage by mitigating hypoxia. It has been speculated that the ischemic
      border zone is a unique area rescued by angiogenic therapy. However, the
      mechanism and timing for new vessel formation in the mammalian heart following
      hypoxia are unclear. Identifying targets that benefit from angiogenesis treatment
      is indispensable for the development of revolutionary therapies. Here, we
      describe a novel circulatory system wherein new vessels develop from the
      endocardium of the left ventricle to perfuse the hypoxic area and salvage damaged
      cardiomyocytes at 3-14 days after MI by activating vascular endothelial growth
      factor signaling. Moreover, enhanced angiogenesis increased cardiomyocyte
      survival along the endocardium in the ischemic zone and suppressed ventricular
      remodeling in infarcted hearts. In contrast, cardiomyocytes in the border zone's
      hypoxic area underwent apoptosis within 12 h of MI, and the border area that was
      amenable to treatment disappeared. These data indicate that the non-perfused area
      along the endocardium is a site of active angiogenesis and a promising target for
      MI treatment.

PMID- 28769051
TI  - IR-laser assisted additive freeform optics manufacturing.
AB  - Computer-controlled additive manufacturing (AM) processes, also known as three
      dimensional (3D) printing, create 3D objects by the successive adding of a
      material or materials. While there have been tremendous developments in AM, the
      3D printing of optics is lagging due to the limits in materials and tight
      requirements for optical applicaitons. We propose a new precision additive
      freeform optics manufacturing (AFOM) method using an pulsed infrared (IR) laser.
      Compared to ultraviolet (UV) curable materials, thermally curable optical
      silicones have a number of advantages, such as strong UV stability, non
      yellowing, and high transmission, making it particularly suitable for optical
      applications. Pulsed IR laser radiation offers a distinct advantage in processing
      optical silicones, as the high peak intensity achieved in the focal region allows
      for curing the material quickly, while the brief duration of the laser-material
      interaction creates a negligible heat-affected zone.

PMID- 28769052
TI  - Femtogram Level Sensitivity achieved by Surface Engineered Silica Nanoparticles
      in the Early Detection of HIV Infection.
AB  - We have engineered streptavidin labelled Europium doped fluorescent silica
      nanoparticles which significantly increased sensitivity without compromising the
      specificity of the immunoassay. As a proof of concept, a time resolved
      fluorescence based sandwich immunoassay was developed to detect HIV-1 p24 antigen
      in clinical specimens. The detection range of the silica nanoparticle based
      immunoassay (SNIA) was found to be between 0.02 to 500 pg/mL in a linear dose
      dependent manner. SNIA offers 1000 fold enhancement over conventional
      colorimetric ELISA. Testing of plasma samples that were HIV negative showed no
      false positive results in the detection of HIV-1 p24 antigen. This highly
      sensitive p24 assay can help improve blood safety by reducing the antibody
      negative window period in blood donors in resource limited settings where nucleic
      acid testing is not practical or feasible. This technology can also be easily
      transferred to a lab-on-a-chip platform for use in resource limited settings and
      can also be easily adopted for the detection of other antigens.

PMID- 28769053
TI  - Link Prediction in Evolving Networks Based on Popularity of Nodes.
AB  - Link prediction aims to uncover the underlying relationship behind networks,
      which could be utilized to predict missing edges or identify the spurious edges.
      The key issue of link prediction is to estimate the likelihood of potential links
      in networks. Most classical static-structure based methods ignore the temporal
      aspects of networks, limited by the time-varying features, such approaches
      perform poorly in evolving networks. In this paper, we propose a hypothesis that
      the ability of each node to attract links depends not only on its structural
      importance, but also on its current popularity (activeness), since active nodes
      have much more probability to attract future links. Then a novel approach named
      popularity based structural perturbation method (PBSPM) and its fast algorithm
      are proposed to characterize the likelihood of an edge from both existing
      connectivity structure and current popularity of its two endpoints. Experiments
      on six evolving networks show that the proposed methods outperform state-of-the
      art methods in accuracy and robustness. Besides, visual results and statistical
      analysis reveal that the proposed methods are inclined to predict future edges
      between active nodes, rather than edges between inactive nodes.

PMID- 28769054
TI  - An alternative microRNA-mediated post-transcriptional regulation of GADD45A by
      p53 in human non-small-cell lung cancer cells.
AB  - GADD45A (growth arrest and DNA damage inducible alpha), a stress response gene
      induced by genotoxic and nongenotoxic stresses, is implicated in various key
      processes, including the control of cell cycle checkpoints and DNA repair. The
      expression of GADD45A is directly regulated by numerous transcription factors,
      with p53 being the most representative. Moreover, post-transcriptional regulation
      also plays a role in GADD45A expression. However, little is known about the
      regulatory effects of microRNAs (miRNAs) on GADD45A expression. As a potential
      tumour suppressor, miR-138 has pleiotropic biological functions in various
      cancers. We have previously reported p53-mediated activation of miR-138 in human
      non-small-cell lung cancer (NSCLC) cells. In this study, we found that miR-138
      specifically targeted AGO2, which affects the stability and maturation of miR
      130b. Decreased expression of miR-130b promoted the expression of GADD45A and
      resulted in the G2/M phase arrest and proliferation inhibition in human NSCLC
      cells. Our results suggested that p53 could alternatively upregulate GADD45A in
      human NSCLC cells through a post-transcriptional pathway in which miR-138 is
      involved.

PMID- 28769055
TI  - High-Coverage Whole-Exome Sequencing Identifies Candidate Genes for Suicide in
      Victims with Major Depressive Disorder.
AB  - We carried out whole-exome ultra-high throughput sequencing in brain samples of
      suicide victims who had suffered from major depressive disorder and control
      subjects who had died from other causes. This study aimed to reveal the selective
      accumulation of rare variants in the coding and the UTR sequences within the
      genes of suicide victims. We also analysed the potential effect of STR and CNV
      variations, as well as the infection of the brain with neurovirulent viruses in
      this behavioural disorder. As a result, we have identified several candidate
      genes, among others three calcium channel genes that may potentially contribute
      to completed suicide. We also explored the potential implication of the TGF-beta
      signalling pathway in the pathogenesis of suicidal behaviour. To our best
      knowledge, this is the first study that uses whole-exome sequencing for the
      investigation of suicide.

PMID- 28769056
TI  - Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role
      in depression-like phenotype.
AB  - Accumulating evidence suggests a role of the ephrin receptor EphA4 and the
      downstream protein ephexin1 in synaptic plasticity, which is implicated in
      depression. We examined whether EphA4-ephexin1 signaling plays a role in the
      pathophysiology of depression, and the antidepressant-like effect of EphA4
      inhibitor rhynchophylline. We found increased ratios of p-EphA4/EphA4 and p
      ephexin1/ephexin1 in the prefrontal cortex (PFC) and hippocampus but not in the
      nucleus accumbens (NAc), of susceptible mice after social defeat stress.
      Furthermore, the p-EphA4/EphA4 ratio was higher in the parietal cortex of
      depressed patients compared with controls. Systemic administration of
      rhynchophylline, produced a rapid antidepressant-like effect in a social defeat
      stress model by inhibiting EphA4-ephexin1 signaling and activating brain-derived
      neurotrophic factor-TrkB signaling in the PFC and hippocampus. Pretreatment with
      rhynchophylline before each social defeat stress could prevent the onset of the
      depression-like phenotype after repeated social defeat stress. Overexpression of
      EphA4 in the medial PFC owing to infection with an EphA4 adeno-associated virus
      caused the depression-like phenotype 3 weeks later and rhynchophylline had a
      rapid antidepressant-like effect in these mice. These findings suggest that
      increased EphA4-ephexin1 signaling in the PFC plays a role in the pathophysiology
      of depression.

PMID- 28769057
TI  - Enhancing Modulation of Thermal Conduction in Vanadium Dioxide Thin Film by
      Nanostructured Nanogaps.
AB  - Efficient thermal management at the nanoscale is important for reducing energy
      consumption and dissipation in electronic devices, lab-on-a-chip platforms and
      energy harvest/conversion systems. For many of these applications, it is much
      desired to have a solid-state structure that reversibly switches thermal
      conduction with high ON/OFF ratios and at high speed. Here we describe design and
      implementation of a novel, all-solid-state thermal switching device by
      nanostructured phase transformation, i.e., modulation of contact pressure and
      area between two poly-silicon surfaces activated by microstructural change of a
      vanadium dioxide (VO2) thin film. Our solid-state devices demonstrate large and
      reversible alteration of cross-plane thermal conductance as a function of
      temperature, achieving a conductance ratio of at least 2.5. Our new approach
      using nanostructured phase transformation provides new opportunities for
      applications that require advanced temperature and heat regulations.

PMID- 28769058
TI  - Characterisation of lung macrophage subpopulations in COPD patients and controls.
AB  - Lung macrophage subpopulations have been identified based on size. We
      investigated characteristics of small and large macrophages in the alveolar
      spaces and lung interstitium of COPD patients and controls. Alveolar and
      interstitial cells were isolated from lung resection tissue from 88 patients.
      Macrophage subpopulation cell-surface expression of immunological markers and
      phagocytic ability were assessed by flow cytometry. Inflammatory related gene
      expression was measured. Alveolar and interstitial macrophages had subpopulations
      of small and large macrophages based on size and granularity. Alveolar
      macrophages had similar numbers of small and large cells; interstitial
      macrophages were mainly small. Small macrophages expressed significantly higher
      cell surface HLA-DR, CD14, CD38 and CD36 and lower CD206 compared to large
      macrophages. Large alveolar macrophages showed lower marker expression in COPD
      current compared to ex-smokers. Small interstitial macrophages had the highest
      pro-inflammatory gene expression levels, while large alveolar macrophages had the
      lowest. Small alveolar macrophages had the highest phagocytic ability. Small
      alveolar macrophage CD206 expression was lower in COPD patients compared to
      smokers. COPD lung macrophages include distinct subpopulations; Small
      interstitial and small alveolar macrophages with more pro-inflammatory and
      phagocytic function respectively, and large alveolar macrophages with low pro
      inflammatory and phagocytic ability.

PMID- 28769059
TI  - Hydrogen physisorption based on the dissociative hydrogen chemisorption at the
      sulphur vacancy of MoS2 surface.
AB  - We provide a new insight that the sulphur-depleted MoS2 surface can store
      hydrogen gas at room temperature. Our findings reveal that the sulphur-vacancy
      defects preferentially serve as active sites for both hydrogen chemisorption and
      physisorption. Unexpectedly the sulphur vacancy instantly dissociates the H2
      molecules and strongly binds the split hydrogen at the exposed Mo atoms. Thereon
      the additional H2 molecule is adsorbed with enabling more hydrogen physisorption
      on the top sites around the sulphur vacancy. Furthermore, the increase of the
      sulphur vacancy on the MoS2 surface further activates the dissociative hydrogen
      chemisorption than the H2 physisorption.

PMID- 28769060
TI  - A diver-operated hyperspectral imaging and topographic surveying system for
      automated mapping of benthic habitats.
AB  - We developed a novel integrated technology for diver-operated surveying of
      shallow marine ecosystems. The HyperDiver system captures rich multifaceted data
      in each transect: hyperspectral and color imagery, topographic profiles, incident
      irradiance and water chemistry at a rate of 15-30 m2 per minute. From surveys in
      a coral reef following standard diver protocols, we show how the rich optical
      detail can be leveraged to generate photopigment abundance and benthic
      composition maps. We applied machine learning techniques, with a minor annotation
      effort (<2% of pixels), to automatically generate cm-scale benthic habitat maps
      of high taxonomic resolution and accuracy (93-97%). The ability to efficiently
      map benthic composition, photopigment densities and rugosity at reef scales is a
      compelling contribution to modernize reef monitoring. Seafloor-level
      hyperspectral images can be used for automated mapping, avoiding operator bias in
      the analysis and deliver the degree of detail necessary for standardized
      environmental monitoring. The technique can deliver fast, objective and economic
      reef survey results, making it a valuable tool for coastal managers and reef
      ecologists. Underwater hyperspectral surveying shares the vantage point of the
      high spatial and taxonomic resolution restricted to field surveys, with
      analytical techniques of remote sensing and provides targeted validation for
      aerial monitoring.

PMID- 28769061
TI  - PARTICLE triplexes cluster in the tumor suppressor WWOX and may extend throughout
      the human genome.
AB  - The long non-coding RNA PARTICLE (Gene PARTICL- 'Promoter of MAT2A-Antisense
      RadiaTion Induced Circulating LncRNA) partakes in triple helix (triplex)
      formation, is transiently elevated following low dose irradiation and regulates
      transcription of its neighbouring gene - Methionine adenosyltransferase 2A. It
      now emerges that PARTICLE triplex sites are predicted in many different genes
      across all human chromosomes. In silico analysis identified additional regions
      for PARTICLE triplexes at >1600 genomic locations. Multiple PARTICLE triplexes
      are clustered predominantly within the human and mouse tumor suppressor WW Domain
      Containing Oxidoreductase (WWOX) gene. Surface plasmon resonance diffraction and
      electrophoretic mobility shift assays were consistent with PARTICLE triplex
      formation within human WWOX with high resolution imaging demonstrating its
      enrichment at this locus on chromosome 16. PARTICLE knockdown and over-expression
      resulted in inverse changes in WWOX transcripts levels with siRNA interference
      eliminating PARTICLEs elevated transcription to irradiation. The evidence for a
      second functional site of PARTICLE triplex formation at WWOX suggests that
      PARTICLE may form triplex-mediated interactions at multiple positions in the
      human genome including remote loci. These findings provide a mechanistic
      explanation for the ability of lncRNAs to regulate the expression of numerous
      genes distributed across the genome.

PMID- 28769062
TI  - Improved electrochemical properties of LiNi0.91Co0.06Mn0.03O2 cathode material
      via Li-reactive coating with metal phosphates.
AB  - Ni-rich layered oxides are promising cathode materials due to their high
      capacities. However, their synthesis process retains a large amount of Li residue
      on the surface, which is a main source of gas generation during operation of the
      battery. In this study, combined with simulation and experiment, we propose the
      optimal metal phosphate coating materials for removing residual Li from the
      surface of the Ni-rich layered oxide cathode material LiNi0.91Co0.06Mn0.03O2.
      First-principles-based screening process for 16 metal phosphates is performed to
      identify an ideal coating material that is highly reactive to Li2O. By
      constructing the phase diagram, we obtain the equilibrium phases from the
      reaction of coating materials and Li2O, based on a database using a DFT hybrid
      functional. Experimental verification for this approach is accomplished with
      Mn3(PO4)2, Co3(PO4)2, Fe3(PO4)2, and TiPO4. The Li-removing capabilities of these
      materials are comparable to the calculated results. In addition, electrochemical
      performances up to 50 charge/discharge cycles show that Mn-, Co-, Fe-phosphate
      materials are superior to an uncoated sample in terms of preventing capacity
      fading behavior, while TiPO4 shows poor initial capacity and rapid reduction of
      capacity during cycling. Finally, Li-containing equilibrium phases examined from
      XRD analysis are in agreement with the simulation results.

PMID- 28769063
TI  - Dynamics of levitated objects in acoustic vortex fields.
AB  - Acoustic levitation in gaseous media provides a tool to process solid and liquid
      materials without the presence of surfaces such as container walls and hence has
      been used widely in chemical analysis, high-temperature processing, drop dynamics
      and bioreactors. To date high-density objects can only be acoustically levitated
      in simple standing-wave fields. Here we demonstrate the ability of a small number
      of peripherally placed sources to generate acoustic vortex fields and stably
      levitate a wide range of liquid and solid objects. The forces exerted by these
      acoustic vortex fields on a levitated water droplet are observed to cause a
      controllable deformation of the droplet and/or oscillation along the vortex axis.
      Orbital angular momentum transfer is also shown to rotate a levitated object
      rapidly and the rate of rotation can be controlled by the source amplitude. We
      expect this research can increase the diversity of acoustic levitation and expand
      the application of acoustic vortices.

PMID- 28769064
TI  - Universal Critical Behaviours in Non-Hermitian Phase Transitions.
AB  - Quantum phase transitions occur in non-Hermitian systems. In this work we show
      that density functional theory, for the first time, uncovers universal critical
      behaviors for quantum phase transitions and quantum entanglement in non-Hermitian
      many-body systems. To be specific, we first prove that the non-degenerate steady
      state of a non-Hermitian quantum many body system is a universal function of the
      first derivative of the steady state energy with respect to the control
      parameter. This finding has far-reaching consequences for non-Hermitian systems.
      First, it bridges the non-analytic behavior of physical observable and no
      analytic behavior of steady state energy, which explains why the quantum phase
      transitions in non-Hermitian systems occur for finite systems. Second, it
      predicts universal scaling behaviors of any physical observable at non-Hermitian
      phase transition point with scaling exponent being (1 - 1/p) with p being the
      number of coalesced states at the exceptional point. Third, it reveals that
      quantum entanglement in non-Hermitian phase transition point presents universal
      scaling behaviors with critical exponents being (1 - 1/p). These results uncover
      universal critical behaviors in non-Hermitian phase transitions and provide
      profound connections between entanglement and phase transition in non-Hermitian
      quantum many-body physics.

PMID- 28769065
TI  - Highly reusable and superhydrophobic spongy graphene aerogels for efficient
      oil/water separation.
AB  - Graphene aerogels (GAs) are three-dimensional (3D) graphene sponges with unique
      wettability and have demonstrated the potential for reducing contamination from
      oil spills and chemical accidents. Herein, we report new polyurethane (PU) sponge
      reinforced GAs with low surface energy, high sorption capacity and excellent
      recyclability for use as efficient oil sorbents. Spongy graphene aerogels (SGAs)
      with a hierarchical porous morphology were produced by simply freeze-casting
      reduced graphene oxide (rGO) to form compacted macroscale sponges. This novel
      micro-structure benefits from the advantages of embedded graphene and presents
      reversible large-strain deformation (90%), high compressive strength (63 kpa) and
      viscoelastic stability. These superior properties, in addition to super
      hydrophobicity, endow the aerogels with excellent recyclability without
      deteriorating the oil absorption performance. Furthermore, SGA has selective and
      high-volume absorbability (>100%) and can efficiently separate oil from water
      under continuous pumping action. The excellent absorption performance and robust
      mechanical properties make this graphene material promising for the large-scale
      recovery of spilled oil.

PMID- 28769067
TI  - 3-D imaging reveals four extraordinary cases of convergent evolution of acoustic
      communication in crickets and allies (Insecta).
AB  - When the same complex trait is exhibited by closely related species, a single
      evolutionary origin is frequently invoked. The complex stridulatory apparatus
      present in the forewings of extant crickets, mole crickets, katydids, and
      prophalangopsids, is currently interpreted as sharing a single common origin due
      to their similarity and unique function. An alternative hypothesis of convergent
      evolution in these ensiferan groups has challenged this common view, but remained
      controversial because of competing interpretations of wing venation. Here we
      propose another hypothesis for the widely and long debated homology of ensiferan
      stridulatory apparatus, performing the first 3D reconstruction of hidden
      structures at the wing bases. This approach allowed defining the homology of each
      vein from its very origin rather than after its more distal characteristics,
      which may be subjected to environmental pressure of selection. The stridulatory
      apparatus involves different veins in these four singing clades. In light of the
      most recent phylogenetic evidence, this apparatus developed four times in
      Ensifera, illustrating extraordinary convergent evolutions between closely
      related clades, by far exceeding the number of evolutionary steps ever proposed
      for calling ability in this group.

PMID- 28769066
TI  - Long-term memory requires sequential protein synthesis in three subsets of
      mushroom body output neurons in Drosophila.
AB  - Creating long-term memory (LTM) requires new protein synthesis to stabilize
      learning-induced synaptic changes in the brain. In the fruit fly, Drosophila
      melanogaster, aversive olfactory learning forms several phases of labile memory
      to associate an odor with coincident punishment in the mushroom body (MB). It
      remains unclear how the brain consolidates early labile memory into LTM. Here, we
      survey 183 Gal4 lines containing almost all 21 distinct types of MB output
      neurons (MBONs) and show that sequential synthesis of learning-induced proteins
      occurs at three types of MBONs. Downregulation of oo18 RNA-binding proteins
      (ORBs) in any of these MBONs impaired LTM. And, neurotransmission outputs from
      these MBONs are all required during LTM retrieval. Together, these results
      suggest an LTM consolidation model in which transient neural activities of early
      labile memory in the MB are consolidated into stable LTM at a few postsynaptic
      MBONs through sequential ORB-regulated local protein synthesis.

PMID- 28769068
TI  - Synergistic Strategy for Multicolor Two-photon Microscopy: Application to the
      Analysis of Germinal Center Reactions In Vivo.
AB  - Simultaneous detection of multiple cellular and molecular players in their native
      environment, one of the keys to a full understanding of immune processes, remains
      challenging for in vivo microscopy. Here, we present a synergistic strategy for
      spectrally multiplexed in vivo imaging composed of (i) triple two-photon
      excitation using spatiotemporal synchronization of two femtosecond lasers, (ii) a
      broad set of fluorophores with emission ranging from blue to near infrared, (iii)
      an effective spectral unmixing algorithm. Using our approach, we simultaneously
      excite and detect seven fluorophores expressed in distinct cellular and tissue
      compartments, plus second harmonics generation from collagen fibers in lymph
      nodes. This enables us to visualize the dynamic interplay of all the central
      cellular players during germinal center reactions. While current in vivo imaging
      typically enables recording the dynamics of 4 tissue components at a time, our
      strategy allows a more comprehensive analysis of cellular dynamics involving 8
      single-labeled compartments. It enables to investigate the orchestration of
      multiple cellular subsets determining tissue function, thus, opening the way for
      a mechanistic understanding of complex pathophysiologic processes in vivo. In the
      future, the design of transgenic mice combining a larger spectrum of fluorescent
      proteins will reveal the full potential of our method.

PMID- 28769069
TI  - Autosomal recessive agammaglobulinemia due to defect in MU heavy chain caused by
      a novel mutation in the IGHM gene.
AB  - Agammaglobulinemia is a primary immunodeficiency disorder characterized by
      profoundly low or absent serum antibodies and low or absent circulating B cells.
      The most common form is X-linked agammaglobulinemia (XLA) caused by mutations in
      BTK gene. The remaining cases, clinically similar to XLA, are autosomal recessive
      agammaglobulinemia (ARA). Nearly 30% of ARA cases present mutations in the MU
      heavy constant region gene IGHM. Here, we present a 7-month-old patient, born
      from non-consanguineous parents, who is affected by ARA due to defect in the MU
      heavy chain. The genetic study showed that the patient is compound heterozygous
      for an IGHM gene deletion and the novel nonsense mutation X57331.1:g.275C>A
      (p.Tyr43*) (ClinVar Accession Number: SCV000537868.1). This finding allows for an
      adequate genetic counseling to the family and also broadens the spectrum of
      already described point mutations at this locus. The IGHM gene is very complex
      and it is likely that yet unidentified mutations appear in other patients.

PMID- 28769070
TI  - IL6R haplotype rs4845625*T/rs4537545*C is a risk factor for simultaneously high
      CRP, LDL and ApoB levels.
AB  - Interleukin 6 receptor (IL-6R), mediating IL-6's biological functions, plays an
      important role in different diseases such as diabetes, obesity and cardio
      vascular diseases. In this study, we investigated the effects of two single
      nucleotide polymorphisms (SNPs), within the IL-6R loci, previously associated
      with C-reactive protein (CRP) and coronary heart diseases risk, and with
      controversial effects on lipids traits: SNP rs4845625 and SNP rs4537545. The
      results showed that both investigated SNPs were antagonistically related with CRP
      levels; the minor rs4845625*T allele was associated with increased CRP levels (P
      value=0.011), while the minor rs4537545*T allele was associated with decreased
      CRP levels (P-value=0.009). Interestingly, the minor rs4845625*T allele was
      significantly associated with higher low-density lipoprotein cholesterol (LDL-C)
      and ApoB levels (P=0.007 and P=0.009 respectively). Haplotype analysis showed
      that the TC haplotype, having the minor rs4845625*T allele, was related
      simultaneously with increased levels of CRP, LDL-C and ApoB levels, thus could be
      considered as a risk factor. Our investigation detects for the first time an
      independent effect of rs4845625 on LDL-C and ApoB traits, explaining an important
      range of those traits variability (3.49 and 5.57% respectively). Our findings
      might be of high clinical significance in pharmacogenomics studies of tocilizumab
      for which IL-6R is target.

PMID- 28769071
TI  - High-quality AlN grown with a single substrate temperature below 1200  degrees C.
AB  - 1.5-MUm AlN grown by metal-organic chemical vapor deposition (MOCVD), with a
      single substrate temperature of 1180  degrees C, exhibits atomically flat surface
      and the XRD (102) peak width of 427 arcsec. The results are achieved with a
      pulsed NH3-flow condition, serving as an alternative for the commonly used
      temperature-varied buffer structure, which is often complicated and time
      consuming. Inserting two pulsed-NH3-flow AlN layers in the epitaxial structure
      not only releases the lattice strain via the formation of three-dimensional nano
      islands, but also smoothens the surface with prolonged lateral migration of Al
      adatoms. This effective growth technique substantially simplifies the manufacture
      of device-quality AlN.

PMID- 28769072
TI  - Post-conventional moral reasoning is associated with increased ventral striatal
      activity at rest and during task.
AB  - People vary considerably in moral reasoning. According to Kohlberg's theory,
      individuals who reach the highest level of post-conventional moral reasoning
      judge moral issues based on deeper principles and shared ideals rather than self
      interest or adherence to laws and rules. Recent research has suggested the
      involvement of the brain's frontostriatal reward system in moral judgments and
      prosocial behaviors. However, it remains unknown whether moral reasoning level is
      associated with differences in reward system function. Here, we combined arterial
      spin labeling perfusion and blood oxygen level-dependent functional magnetic
      resonance imaging and measured frontostriatal reward system activity both at rest
      and during a sequential risky decision making task in a sample of 64 participants
      at different levels of moral reasoning. Compared to individuals at the pre
      conventional and conventional level of moral reasoning, post-conventional
      individuals showed increased resting cerebral blood flow in the ventral striatum
      and ventromedial prefrontal cortex. Cerebral blood flow in these brain regions
      correlated with the degree of post-conventional thinking across groups. Post
      conventional individuals also showed greater task-induced activation in the
      ventral striatum during risky decision making. These findings suggest that high
      level post-conventional moral reasoning is associated with increased activity in
      the brain's frontostriatal system, regardless of task-dependent or task
      independent states.

PMID- 28769073
TI  - Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial
      Nitric Oxide Synthase Gene Knockout Mice.
AB  - Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) plays an
      important role in the maintenance of ocular vascular homeostasis. Therefore,
      perturbations in vascular NO synthesis have been implicated in the pathogenesis
      of several ocular diseases. We recently reported that eNOS contributes
      significantly to vasodilation of the mouse ophthalmic artery. Interestingly,
      dilatory responses were also retained in eNOS gene-deficient mice (eNOS-/-),
      indicating inherent endothelial adaptive mechanism(s) that act as back-up systems
      in chronic absence of eNOS to preserve vasorelaxation. Thus, this study
      endeavoured to identify the compensatory mechanism(s) in the ophthalmic artery of
      eNOS-/- mice employing isolated arterial segments and pharmacological inhibitors
      in vitro. Endothelium removal virtually abolished acetylcholine (ACh)-induced
      vasodilation, suggesting an obligatory involvement of the endothelium in
      cholinergic control of vascular tone. However, non-NOS and non-cyclooxygenase
      components compensate for eNOS deficiency via endothelium-derived hyperpolarizing
      factors (EDHFs). Notably, arachidonic acid-derived metabolites of the 12
      lipoxygenase pathway were key mediators in activating the inwardly rectifying
      potassium channels to compensate for chronic lack of eNOS. Conclusively,
      endothelium-dependent cholinergic responses of the ophthalmic artery in the eNOS
      /- mice are largely preserved and, this vascular bed has the ability to
      compensate for the loss of normal vasodilator responses solely via EDHFs.

PMID- 28769074
TI  - Genetic and constitutional factors are major contributors to substantia nigra
      hyperechogenicity.
AB  - Hyperechogenicity of substantia nigra (SNh) is a frequent finding in amyotrophic
      lateral sclerosis (ALS), Parkinson's disease (PD) and other movement disorders
      (MD) patients, but its meaning is unclear. To ascertain the contribution of
      different factors to SNh area, we measured it in 108 ALS, 102 PD, 91 other MD
      patients and 91 healthy controls. Demographical data were collected in all
      patients and controls. In ALS patients, we also recorded clinical variables,
      performed genetic analysis and measured baseline levels of ferritin. After family
      history and genetic testing, ALS patients were classified as familial (15) or
      sporadic (93). ALS, PD and other MD patients had a larger SNh area than controls.
      Left SNh and male gender, but not age, associated with larger SNh area in both
      patients and controls. Familial ALS patients showed larger SNh area than sporadic
      ones and familial ALS was the only clinical variable in the multivariate analysis
      to be associated with larger SNh area in ALS patients. Our results suggest that
      SNh associates with genetic and constitutional factors (male gender, handedness),
      some of which predispose to certain neurodegenerative diseases. This evidence
      supports the idea of SNh as an inborn marker of unspecific neuronal
      vulnerability.

PMID- 28769075
TI  - Changes in the soil organic carbon balance on China's cropland during the last
      two decades of the 20th century.
AB  - Agro-ecosystems play an important role in regulating global changes caused by
      greenhouse gas emissions. Restoration of soil organic carbon (SOC) in
      agricultural soils can not only improve soil quality but also influence climate
      change and agronomic productivity. With about half of its land area under
      agricultural use, China exhibits vast potential for carbon (C) sequestration that
      needs to be researched. Chinese cropland has experienced SOC change over the past
      century. The study of SOC dynamics under different bioclimatic conditions and
      cropping systems can help us to better understand this historical change, current
      status, the impacts of bioclimatic conditions on SOC and future trends. We used a
      simulation based on historical statistical data to analyze the C balance of
      Chinese croplands during the 1980s and 1990s, taking into account soil, climate
      and agricultural management. Nationwide, 77.6% of the national arable land is
      considered to be in good condition. Appropriate farm management practices should
      be adopted to improve the poor C balance of the remaining 22.4% of cropland to
      promote C sequestration.

PMID- 28769077
TI  - Nanosecond laser coloration on stainless steel surface.
AB  - In this work, we present laser coloration on 304 stainless steel using nanosecond
      laser. Surface modifications are tuned by adjusting laser parameters of scanning
      speed, repetition rate, and pulse width. A comprehensive study of the physical
      mechanism leading to the appearance is presented. Microscopic patterns are
      measured and employed as input to simulate light-matter interferences, while
      chemical states and crystal structures of composites to figure out intrinsic
      colors. Quantitative analysis clarifies the final colors and RGB values are the
      combinations of structural colors and intrinsic colors from the oxidized
      pigments, with the latter dominating. Therefore, the engineering and scientific
      insights of nanosecond laser coloration highlight large-scale utilization of the
      present route for colorful and resistant steels.

PMID- 28769076
TI  - Connexin 43 is required for the maintenance of mitochondrial integrity in brown
      adipose tissue.
AB  - We investigated the role of connexin 43 (Cx43) in maintaining the integrity of
      mitochondria in brown adipose tissue (BAT). The functional effects of Cx43 were
      evaluated using inducible, adipocyte-specific Cx43 knockout in mice (Gja1 adipoq
      KO) and by overexpression and knockdown of Cx43 in cultured adipocytes.
      Mitochondrial morphology was evaluated by electron microscopy and mitochondrial
      function and autophagy were assessed by immunoblotting, immunohistochemistry, and
      qPCR. The metabolic effects of adipocyte-specific knockout of Cx43 were assessed
      during cold stress and following high fat diet feeding. Cx43 expression was
      higher in BAT compared to white adipose tissue. Treatment with the beta3
      adrenergic receptor agonist CL316,243 increased Cx43 expression and mitochondrial
      localization. Gja1 adipoq KO mice reduced mitochondrial density and increased the
      presence of damaged mitochondria in BAT. Moreover, metabolic activation with
      CL316,243 further reduced mitochondrial integrity and upregulated autophagy in
      the BAT of Gja1 adipoq KO mice. Inhibition of Cx43 in cultured adipocytes
      increased the generation of reactive oxygen species and induction of autophagy
      during beta-adrenergic stimulation. Gja1 adipoq KO mice were cold intolerant,
      expended less energy in response to beta3-adrenergic receptor activation, and
      were more insulin resistant after a high-fat diet challenge. Collectively, our
      data demonstrate that Cx43 is required for maintaining the mitochondrial
      integrity and metabolic activity of BAT.

PMID- 28769078
TI  - Assessment of a novel bile solubility test and MALDI-TOF for the differentiation
      of Streptococcus pneumoniae from other mitis group streptococci.
AB  - This study assesses a novel bile solubility test and MALDI-TOF for the
      differentiation of Streptococcus pneumoniae from other mitis group streptococci,
      including differentiation of S. pneumoniae from Streptococcus pseudopneumoniae.
      Eighty-four species verified mitis group isolates were subjected to our bile
      solubility test (which measures and calculates the differences of absorbance in
      the test tube containing 10% sodium deoxycholate versus a blank control tube,
      after incubation for 10 minutes at 36  degrees C using a spectrophotometer) and
      MALDI-TOF MS (both the standard result output and by visual spectra evaluation).
      Applying a calculated optimal cut-off absorbance-value of 2.1, differentiated S.
      pneumoniae from all but one other mitis group streptococci (one S. mitis isolate
      generated an OD-value above 2.1). MALDI-TOF score value identification identified
      correctly 46 S. pneumoniae and 4 S. pseudopneumoniae but misidentified 16 other
      mitis group strains. Visual spectra evaluation correctly identified all S.
      pneumoniae and S. pseudopneumoniae strains but misidentified 13 other mitis group
      strains. The bile solubility test based on spectrophotometric reading described
      in this study can differentiate S. pneumoniae from other Streptococcus species.
      Combining the bile solubility test and the MALDI-TOF spectra results provide a
      correct identification of all S. pneumoniae and S. pseudopneumoniae isolates.

PMID- 28769079
TI  - Ecological Network Inference From Long-Term Presence-Absence Data.
AB  - Ecological communities are characterized by complex networks of trophic and
      nontrophic interactions, which shape the dy-namics of the community. Machine
      learning and correlational methods are increasingly popular for inferring
      networks from co-occurrence and time series data, particularly in microbial
      systems. In this study, we test the suitability of these methods for inferring
      ecological interactions by constructing networks using Dynamic Bayesian Networks,
      Lasso regression, and Pear-son's correlation coefficient, then comparing the
      model networks to empirical trophic and nontrophic webs in two ecological
      systems. We find that although each model significantly replicates the structure
      of at least one empirical network, no model significantly predicts network
      structure in both systems, and no model is clearly superior to the others. We
      also find that networks inferred for the Tatoosh intertidal match the nontrophic
      network much more closely than the trophic one, possibly due to the challenges of
      identifying trophic interactions from presence-absence data. Our findings suggest
      that although these methods hold some promise for ecological network inference,
      presence-absence data does not provide enough signal for models to consistently
      identify interactions, and networks inferred from these data should be
      interpreted with caution.

PMID- 28769080
TI  - Few basepairing-independent motifs in the apical half of the avian HBV epsilon
      RNA stem-loop determine site-specific initiation of protein-priming.
AB  - Hepadnaviruses, including human hepatitis B virus (HBV), replicate their tiny DNA
      genomes by protein-primed reverse transcription of a pregenomic (pg) RNA.
      Replication initiation as well as pgRNA encapsidation depend on the interaction
      of the viral polymerase, P protein, with the epsilon RNA element, featuring a
      lower and an upper stem, a central bulge, and an apical loop. The bulge, somehow
      assisted by the loop, acts as template for a P protein-linked DNA oligo that
      primes full-length minus-strand DNA synthesis. Phylogenetic conservation and
      earlier mutational studies suggested the highly based-paired epsilon structure as
      crucial for productive interaction with P protein. Using the tractable duck HBV
      (DHBV) model we here interrogated the entire apical DHBV epsilon (Depsilon) half
      for sequence- and structure-dependent determinants of in vitro priming activity,
      replication, and, in part, in vivo infectivity. This revealed single-strandedness
      of the bulge, a following G residue plus the loop subsequence GUUGU as the few
      key determinants for priming and initiation site selection; unexpectedly, they
      functioned independently of a specific structure context. These data provide new
      mechanistic insights into avihepadnaviral replication initiation, and they imply
      a new concept towards a feasible in vitro priming system for human HBV.

PMID- 28769081
TI  - Lifetime self-reported arthritis is associated with elevated levels of mental
      health burden: A multi-national cross sectional study across 46 low- and middle
      income countries.
AB  - Population-based studies investigating the relationship of arthritis with mental
      health outcomes are lacking, particularly among low- and middle-income countries
      (LMICs). We investigated the relationship between arthritis and mental health
      (depression spectrum, psychosis spectrum, anxiety, sleep disturbances and stress)
      across community-dwelling adults aged >=18 years across 46 countries from the
      World Health Survey. Symptoms of psychosis and depression were established using
      questions from the Mental Health Composite International Diagnostic Interview.
      Severity of anxiety, sleep problems, and stress sensitivity over the preceding 30
      days were self-reported. Self-report lifetime history of arthritis was collected,
      including presence or absence of symptoms suggestive of arthritis: pain,
      stiffness or swelling of joints over the preceding 12-months. Multivariable
      logistic regression analyses were undertaken. Overall, 245,706 individuals were
      included. Having arthritis increased the odds of subclinical psychosis (OR =
      1.85; 95%CI = 1.72-1.99) and psychosis (OR = 2.48; 95%CI = 2.05-3.01). People
      with arthritis were at increased odds of subsyndromal depression (OR = 1.92;
      95%CI = 1.64-2.26), a brief depressive episode (OR = 2.14; 95%CI = 1.88-2.43) or
      depressive episode (OR = 2.43; 95%CI = 2.21-2.67). Arthritis was also associated
      with increased odds for anxiety (OR = 1.75; 95%CI = 1.63-1.88), sleep problems
      (OR = 2.23; 95%CI = 2.05-2.43) and perceived stress (OR = 1.43; 95%CI = 1.33
      1.53). Results were similar for middle-income and low-income countries.
      Integrated interventions addressing arthritis and mental health comorbidities are
      warranted to tackle this considerable burden.

PMID- 28769082
TI  - Neural substrates of embodied natural beauty and social endowed beauty: An fMRI
      study.
AB  - What are the neural mechanisms underlying beauty based on objective parameters
      and beauty based on subjective social construction? This study scanned
      participants with fMRI while they performed aesthetic judgments on concrete
      pictographs and abstract oracle bone scripts. Behavioral results showed both
      pictographs and oracle bone scripts were judged to be more beautiful when they
      referred to beautiful objects and positive social meanings, respectively. Imaging
      results revealed regions associated with perceptual, cognitive, emotional and
      reward processing were commonly activated both in beautiful judgments of
      pictographs and oracle bone scripts. Moreover, stronger activations of
      orbitofrontal cortex (OFC) and motor-related areas were found in beautiful
      judgments of pictographs, whereas beautiful judgments of oracle bone scripts were
      associated with putamen activity, implying stronger aesthetic experience and
      embodied approaching for beauty were elicited by the pictographs. In contrast,
      only visual processing areas were activated in the judgments of ugly pictographs
      and negative oracle bone scripts. Results provide evidence that the sense of
      beauty is triggered by two processes: one based on the objective parameters of
      stimuli (embodied natural beauty) and the other based on the subjective social
      construction (social endowed beauty).

PMID- 28769083
TI  - Human adipose-derived mesenchymal stem cells seeded into a collagen
      hydroxyapatite scaffold promote bone augmentation after implantation in the
      mouse.
AB  - Traumatic injury or surgical excision of diseased bone tissue usually require the
      reconstruction of large bone defects unable to heal spontaneously, especially in
      older individuals. This is a big challenge requiring the development of
      biomaterials mimicking the bone structure and capable of inducing the right
      commitment of cells seeded within the scaffold. In particular, given their
      properties and large availability, the human adipose-derived stem cells are
      considered as the better candidate for autologous cell transplantation. In order
      to evaluate the regenerative potential of these cells along with an
      osteoinductive biomaterial, we have used collagen/hydroxyapatite scaffolds to
      test ectopic bone formation after subcutaneous implantation in mice. The process
      was analysed both in vivo, by Fluorescent Molecular Tomography (FMT), and ex
      vivo, to evaluate the formation of bone and vascular structures. The results have
      shown that the biomaterial could itself be able of promoting differentiation of
      host cells and bone formation, probably by means of its intrinsic chemical and
      structural properties, namely the microenvironment. However, when charged with
      human mesenchymal stem cells, the ectopic bone formation within the scaffold was
      increased. We believe that these results represent an important advancement in
      the field of bone physiology, as well as in regenerative medicine.

PMID- 28769084
TI  - Antibody-induced dimerization of FGFR1 promotes receptor endocytosis
      independently of its kinase activity.
AB  - Fibroblast growth factors (FGFs) and their plasma membrane-localized receptors
      (FGFRs) play a key role in the regulation of developmental processes and
      metabolism. Aberrant FGFR signaling is associated with the progression of serious
      metabolic diseases and human cancer. Binding of FGFs to FGFRs induces receptor
      dimerization and transphosphorylation of FGFR kinase domains that triggers
      activation of intracellular signaling pathways. Following activation, FGFRs
      undergo internalization and subsequent lysosomal degradation, which terminates
      transmission of signals. Although factors that regulate FGFR endocytosis are
      continuously discovered, little is known about the molecular mechanism that
      initiates the internalization of FGFRs. Here, we analyzed the internalization of
      antibody fragments in various formats that target FGFR1. We show that FGFR1
      specific antibody fragments in the monovalent scFv format bind to FGFR1, but are
      not internalized into cells that overproduce FGFR1. In contrast, the same scFv
      proteins in the bivalent scFv-Fc format are efficiently internalized via FGFR1
      mediated, clathrin and dynamin dependent endocytosis. Interestingly, the receptor
      tyrosine kinase activity is dispensable for endocytosis of scFv-Fc-FGFR1
      complexes, suggesting that only dimerization of receptor is required to trigger
      endocytosis of FGFR1 complexes.

PMID- 28769085
TI  - Patterns and drivers of daily bed-level dynamics on two tidal flats with
      contrasting wave exposure.
AB  - Short-term bed-level dynamics has been identified as one of the main factors
      affecting biota establishment or retreat on tidal flats. However, due to a lack
      of proper instruments and intensive labour involved, the pattern and drivers of
      daily bed-level dynamics are largely unexplored in a spatiotemporal context. In
      this study, 12 newly-developed automatic bed-level sensors were deployed for
      nearly 15 months on two tidal flats with contrasting wave exposure, proving an
      unique dataset of daily bed-level changes and hydrodynamic forcing. By analysing
      the data, we show that (1) a general steepening trend exists on both tidal flats,
      even with contrasting wave exposure and different bed sediment grain size; (2)
      daily morphodynamics level increases towards the sea; (3) tidal forcing sets the
      general morphological evolution pattern at both sites; (4) wave forcing induces
      short-term bed-level fluctuations at the wave-exposed site, but similar effect is
      not seen at the sheltered site with smaller waves; (5) storms provoke aggravated
      erosion, but the impact is conditioned by tidal levels. This study provides
      insights in the pattern and drivers of daily intertidal bed-level dynamics,
      thereby setting a template for future high-resolution field monitoring programmes
      and inviting in-depth morphodynamic modelling for improved understanding and
      predictive capability.

PMID- 28769087
TI  - Bifunctional hydrous RuO2 nanocluster electrocatalyst embedded in carbon matrix
      for efficient and durable operation of rechargeable zinc-air batteries.
AB  - Ruthenium oxide (RuO2) is the best oxygen evolution reaction (OER)
      electrocatalyst. Herein, we demonstrated that RuO2 can be also efficiently used
      as an oxygen reduction reaction (ORR) electrocatalyst, thereby serving as a
      bifunctional material for rechargeable Zn-air batteries. We found two forms of
      RuO2 (i.e. hydrous and anhydrous, respectively h-RuO2 and ah-RuO2) to show
      different ORR and OER electrocatalytic characteristics. Thus, h-RuO2 required
      large ORR overpotentials, although it completed the ORR via a 4e process. In
      contrast, h-RuO2 triggered the OER at lower overpotentials at the expense of
      showing very unstable electrocatalytic activity. To capitalize on the advantages
      of h-RuO2 while improving its drawbacks, we designed a unique structure (RuO2@C)
      where h-RuO2 nanoparticles were embedded in a carbon matrix. A double hydrophilic
      block copolymer-templated ruthenium precursor was transformed into RuO2
      nanoparticles upon formation of the carbon matrix via annealing. The carbon
      matrix allowed overcoming the limitations of h-RuO2 by improving its poor
      conductivity and protecting the catalyst from dissolution during OER. The
      bifunctional RuO2@C catalyst demonstrated a very low potential gap (DeltaE OER
      ORR = ca. 1.0 V) at 20 mA cm-2. The Zn||RuO2@C cell showed an excellent stability
      (i.e. no overpotential was observed after more than 40 h).

PMID- 28769086
TI  - Intergenerational Transmission of Paternal Epigenetic Marks: Mechanisms
      Influencing Susceptibility to Post-Concussion Symptomology in a Rodent Model.
AB  - Epigenetic transmission of phenotypic variance has been linked to paternal
      experiences prior to conception and during perinatal development. Previous
      reports indicate that paternal experiences increase phenotypic heterogeneity and
      may contribute to offspring susceptibility to post-concussive symptomology. This
      study sought to determine if epigenetic tags, specifically DNA methylation of
      promoter regions, are transmitted from rodent fathers to their sons. Using
      MethyLight, promoter methylation of specific genes involved in recovery from
      concussion and brain plasticity were analyzed in sperm and brain tissue. Promoter
      methylation in sperm differed based on paternal experience. Differences in
      methylation were often identified in both the sperm and brain tissue obtained
      from their sons, demonstrating transmission of epigenetic tags. For certain
      genes, methylation in the sperm was altered following a concussion suggesting
      that a history of brain injury may influence paternal transmission of traits. As
      telomere length is paternally inherited and linked to neurological health, this
      study examined paternally derived differences in telomere length, in both sperm
      and brain. Telomere length was consistent between fathers and their sons, and
      between brain and sperm, with the exception of the older fathers. Older fathers
      exhibited increased sperm telomere length, which was not evident in sperm or
      brain of their sons.

PMID- 28769088
TI  - Influence of the asymmetric excited state decay on coherent population trapping.
AB  - Electromagnetically induced transparency (EIT) is an optical phenomenon which
      allows a drastic modification of the optical properties of an atomic system by
      applying a control field. It has been largely studied in the last decades and
      nowadays we can find a huge number of experimental and theoretical related
      studies. Recently a similar phenomenon was also shown in quantum dot molecules
      (QDM), where the control field is replaced by the tunneling rate between quantum
      dots. Our results show that in the EIT regime, the optical properties of QDM and
      the atomic system are identical. However, here we show that in the strong probe
      field regime, i.e., "coherent population trapping" (CPT) regime, it appears a
      strong discrepancy on the optical properties of both systems. We show that the
      origin of such difference relies on the different decay rates of the excited
      state of the two systems, implying in a strong difference on their higher order
      nonlinear susceptibilities. Finally, we investigate the optical response of
      atom/QDM strongly coupled to a cavity mode. In particular, the QDM-cavity system
      has the advantage of allowing a better narrowing of the width of the dark state
      resonance in the CPT regime when compared with atom-cavity system.

PMID- 28769089
TI  - Joint effect of ageing and multilayer structure prevents ordering in the voter
      model.
AB  - The voter model rules are simple, with agents copying the state of a random
      neighbor, but they lead to non-trivial dynamics. Besides opinion processes, the
      model has also applications for catalysis and species competition. Inspired by
      the temporal inhomogeneities found in human interactions, one can introduce
      ageing in the agents: the probability to update their state decreases with the
      time elapsed since the last change. This modified dynamics induces an approach to
      consensus via coarsening in single-layer complex networks. In this work, we
      investigate how a multilayer structure affects the dynamics of the ageing voter
      model. The system is studied as a function of the fraction of nodes sharing
      states across layers (multiplexity parameter q). We find that the dynamics of the
      system suffers a notable change at an intermediate value q*. Above it, the voter
      model always orders to an absorbing configuration. While below it a fraction of
      the realizations falls into dynamical traps associated to a spontaneous symmetry
      breaking. In this latter case, the majority opinion in the different layers takes
      opposite signs and the arrival at the absorbing state is indefinitely delayed due
      to ageing.

PMID- 28769090
TI  - Discovery of novel therapeutic properties of drugs from transcriptional responses
      based on multi-label classification.
AB  - Drug repositioning strategies have improved substantially in recent years. At
      present, two advances are poised to facilitate new strategies. First, the LINCS
      project can provide rich transcriptome data that reflect the responses of cells
      upon exposure to various drugs. Second, machine learning algorithms have been
      applied successfully in biomedical research. In this paper, we developed a
      systematic method to discover novel indications for existing drugs by approaching
      drug repositioning as a multi-label classification task and used a Softmax
      regression model to predict previously unrecognized therapeutic properties of
      drugs based on LINCS transcriptome data. This approach to complete the said task
      has not been achieved in previous studies. By performing in silico comparison, we
      demonstrated that the proposed Softmax method showed markedly superior
      performance over those of other methods. Once fully trained, the method showed a
      training accuracy exceeding 80% and a validation accuracy of approximately 70%.
      We generated a highly credible set of 98 drugs with high potential to be
      repositioned for novel therapeutic purposes. Our case studies included zonisamide
      and brinzolamide, which were originally developed to treat indications of the
      nervous system and sensory organs, respectively. Both drugs were repurposed to
      the cardiovascular category.

PMID- 28769091
TI  - Removal of Copper (II) by Biochar Mediated by Dissolved Organic Matter.
AB  - The effects of humic acid (HA) and fulvic acid (FA) on Cu2+ adsorption on biochar
      were investigated, with mechanisms confirmed by excitation-emission matrix
      spectroscopy, Fourier transform infrared spectroscopy, and scanning electron
      microscopy. HA loading enhanced Cu2+ adsorption on biochar, with the maximum
      enhancement of 55.0% occurring at an HA loading of 100 mg-C/L. The adsorbed HA
      introduced many additional functional groups to biochar, thus enhancing Cu2+
      adsorption, which decreased at HA concentrations >100 mg-C/L due to self
      association of HA at high loading concentrations. In contrast, FA loading caused
      no enhancement on Cu2+ adsorption on biochar. FA was adsorbed through H-bonding
      with the functional groups of biochar, which set up a competition with Cu2+ for
      adsorption on biochar. The functional groups occupied by adsorbed FA were offset
      by the newly introduced functional groups of FA, thus there was no net increase
      in the amount of Cu2+ adsorption upon FA loading. These findings imply that,
      because of the enhanced adsorption of HA-loaded biochar, the amount of Cu2+
      immobilized would increase by 28.2% for mature compost and 31.9% for fresh
      compost if there exist interaction between biochar and HA compared with the
      amounts immobilized by non-interactive HA and biochar.

PMID- 28769092
TI  - Unprecedented heat wave in December 2015 and potential for winter glacier
      ablation in the eastern Alps.
AB  - We document the occurrence in December 2015 of unprecedented high monthly mean
      temperatures in the observational record of mountain sites in the eastern Alps.
      For the first time in the last 150 years mean December temperature exceeded 0 
      degrees C at elevations between 2100 and 2500 m, with December mean anomalies
      exceeding 6.5  degrees C with respect to the 1971-2000 mean. Along with the
      absence of snow cover, such temperatures might have lead to unprecedented winter
      ablation of glaciers in this elevation range. Smaller temperature anomalies
      occurred in surrounding low elevation sites, highlighting the key role of
      topography in this event. Specifically, strong inversions associated with the
      very stable synoptic conditions during the month amplified the anomalies at the
      high elevations of the mountain glacier sites. We analyze the processes
      underlying this exceptional event and place this anomaly within the context of
      future warming scenarios over the region.

PMID- 28769093
TI  - Determination of critical cooling rates in metallic glass forming alloy libraries
      through laser spike annealing.
AB  - The glass forming ability (GFA) of metallic glasses (MGs) is quantified by the
      critical cooling rate (R C). Despite its key role in MG research, experimental
      challenges have limited measured R C to a minute fraction of known glass formers.
      We present a combinatorial approach to directly measure R C for large
      compositional ranges. This is realized through the use of compositionally-graded
      alloy libraries, which were photo-thermally heated by scanning laser spike
      annealing of an absorbing layer, then melted and cooled at various rates. Coupled
      with X-ray diffraction mapping, GFA is determined from direct R C measurements.
      We exemplify this technique for the Au-Cu-Si system, where we identify
      Au56Cu27Si17 as the alloy with the highest GFA. In general, this method enables
      measurements of R C over large compositional areas, which is powerful for
      materials discovery and, when correlating with chemistry and other properties,
      for a deeper understanding of MG formation.

PMID- 28769094
TI  - Enhanced Performance of GaN-based Ultraviolet Light Emitting Diodes by Photon
      Recycling Using Graphene Quantum Dots.
AB  - Graphene quantum dots (GQDs) with an average diameter of 3.5 nm were prepared via
      pulsed laser ablation. The synthesized GQDs can improve the optical and
      electrical properties of InGaN/InAlGaN UV light emitting diodes (LEDs)
      remarkably. An enhancement of electroluminescence and a decrease of series
      resistance of LEDs were observed after incorporation of GQDs on the LED surface.
      As the GQD concentration is increased, the emitted light (series resistance) in
      the LED increases (decreases) accordingly. The light output power achieved a
      maximum increase as high as 71% after introducing GQDs with the concentration of
      0.9 mg/ml. The improved performance of LEDs after the introduction of GQDs is
      explained by the photon recycling through the light extraction from the waveguide
      mode and the carrier transfer from GQDs to the active layer.

PMID- 28769095
TI  - Increased dopamine release after working-memory updating training: Neurochemical
      correlates of transfer.
AB  - Previous work demonstrates that working-memory (WM) updating training results in
      improved performance on a letter-memory criterion task, transfers to an untrained
      n-back task, and increases striatal dopamine (DA) activity during the criterion
      task. Here, we sought to replicate and extend these findings by also examining
      neurochemical correlates of transfer. Four positron emission tomography (PET)
      scans using the radioligand raclopride were performed. Two of these assessed DAD2
      binding (letter memory; n-back) before 5 weeks of updating training, and the same
      two scans were performed post training. Key findings were (a) pronounced training
      related behavioral gains in the letter-memory criterion task, (b) altered
      striatal DAD2 binding potential after training during letter-memory performance,
      suggesting training-induced increases in DA release, and (c) increased striatal
      DA activity also during the n-back transfer task after the intervention, but no
      concomitant behavioral transfer. The fact that the training-related DA
      alterations during the transfer task were not accompanied by behavioral transfer
      suggests that increased DA release may be a necessary, but not sufficient,
      condition for behavioral transfer to occur.

PMID- 28769096
TI  - Refractory period in network models of excitable nodes: self-sustaining stable
      dynamics, extended scaling region and oscillatory behavior.
AB  - Networks of excitable nodes have recently attracted much attention particularly
      in regards to neuronal dynamics, where criticality has been argued to be a
      fundamental property. Refractory behavior, which limits the excitability of
      neurons is thought to be an important dynamical property. We therefore consider a
      simple model of excitable nodes which is known to exhibit a transition to
      instability at a critical point (lambda = 1), and introduce refractory period
      into its dynamics. We use mean-field analytical calculations as well as numerical
      simulations to calculate the activity dependent branching ratio that is useful to
      characterize the behavior of critical systems. We also define avalanches and
      calculate probability distribution of their size and duration. We find that in
      the presence of refractory period the dynamics stabilizes while various parameter
      regimes become accessible. A sub-critical regime with lambda < 1.0, a standard
      critical behavior with exponents close to critical branching process for lambda =
      1, a regime with 1 < lambda < 2 that exhibits an interesting scaling behavior,
      and an oscillating regime with lambda > 2.0. We have therefore shown that
      refractory behavior leads to a wide range of scaling as well as periodic behavior
      which are relevant to real neuronal dynamics.

PMID- 28769097
TI  - The association between structure-function relationships and cognitive impairment
      in elderly glaucoma patients.
AB  - Accurate measurement of visual field (VF) is important in accessing glaucoma,
      however this may not be achieved in patients with dementia or mild cognitive
      impairment (CI). We investigated the association between CI and structure
      function relationships in elderly glaucoma patients. The study included 94 eyes
      of 51 glaucoma patients aged >=75 years with no diagnoses of dementia. CI was
      assessed using the Mini Mental State Examination (MMSE). Using the leave-one-out
      cross-validation, the mean deviation (MD) of the Humphrey 30-2 VF was predicted
      from measurements of optical coherence tomography, and the relationship between
      the squared prediction error and the MMSE score, together with age, fixation loss
      (FL), false positive (FP), and false negative (FN) percentages that were analyzed
      using the linear mixed model. A high prevalence of MCI or dementia was observed
      in the elderly population. The squared prediction error value of the MD was 17.0
      +/- 21.1 (mean +/- standard deviation). The squared prediction error increased
      with decreasing MMSE total score, but age, FL, FP, and FN were not related.
      Careful consideration is needed when interpreting the VF results of these
      patients, because VF can be over- or underestimated, as suggested by the
      decreased structure-function relationships.

PMID- 28769098
TI  - The role of artificial root exudate components in facilitating the degradation of
      pyrene in soil.
AB  - Root exudates play an important role in the phytoremediation of soils
      contaminated by organic pollutants, but how root exudate components affect the
      remediation process is not well understood. In this study, we explored the
      effects and mechanisms of the major root exudates, including glucose, organic
      acids, and serine, in the rhizoremediation of pyrene-contaminated soil. The
      results showed that glucose increased the degradation of pyrene (54.3 +/- 1.7%)
      most significantly compared to the organic acids (45.5 +/- 2.5%) and serine (43.2
      +/- 0.1%). Glucose could significantly facilitate the removal of pyrene in soil
      through promoting dehydrogenase activity indicated by a positive correlation
      between the removal efficiency of pyrene and the soil dehydrogenase activity (p <
      0.01). Furthermore, root exudates were able to change soil microbial community,
      particularly the bacterial taxonomic composition, thereby affecting the
      biodegradation of pyrene. Glucose could alter soil microbial community and
      enhance the amount of Mycobacterium markedly, which is dominant in the
      degradation of pyrene. These findings provide insights into the mechanisms by
      which root exudates enhance the degradation of organic contaminants and advance
      our understanding of the micro-processes involved in rhizoremediation.

PMID- 28769099
TI  - Thermoneutral housing temperature regulates T-regulatory cell function and
      inhibits ovabumin-induced asthma development in mice.
AB  - The change in ambient temperature is one of the risk factors for the aggravation
      of bronchial asthma (BA). Yet, whether the ambient temperature influences the
      immune functions associated with allergic asthma remains unknown. In this study,
      we treated asthmatic mice with standard temperature (ST, 20  degrees C) or
      thermoneutral temperature (TT, 30  degrees C). The results showed that the airway
      inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and airway
      hyperresponsiveness (AHR) were significantly reduced in the mice treated with TT
      as compared with the mice treated with ST. The imbalance of Th1/Th2 response in
      the lung was improved following housing the mice at TT. In addition, the
      pulmonary Treg cells were increased in asthmatic mice after TT treatment. The
      temperature stress (29  degrees C and 41  degrees C) drove naive CD4T cells
      towards Th2 cells. Our data demonstrate that the change of ambient temperature
      was a risk factor to aggravate experimental asthma.

PMID- 28769100
TI  - Resistance training alone reduces systolic and diastolic blood pressure in
      prehypertensive and hypertensive individuals: meta-analysis.
AB  - The purpose of this study was to evaluate the effects of resistance training
      alone on the systolic and diastolic blood pressure in prehypertensive and
      hypertensive individuals. Our meta-analysis, followed the guidelines of PRISMA.
      The search for articles was realized by November 2016 using the following
      electronic databases: BIREME, PubMed, Cochrane Library, LILACS and SciELO and a
      search strategy that included the combination of titles of medical affairs and
      terms of free text to the key concepts: 'hypertension' 'hypertensive',
      'prehypertensive', 'resistance training', 'strength training', and 'weight
      lifting'. These terms were combined with a search strategy to identify randomized
      controlled trials (RCTs) and identified a total of 1608 articles: 644 articles
      BIREME, 53 SciELO, 722 PubMed, 122 Cochrane Library and 67 LILACS. Of these, five
      RCTs met the inclusion criteria and provided data on 201 individuals. The results
      showed significant reductions for systolic blood pressure (-8.2 mm Hg CI -10.9 to
      -5.5;I2: 22.5% P valor for heterogeneity=0.271 and effect size=-0.97) and
      diastolic blood pressure (-4.1 mm Hg CI -6.3 to -1.9; I2: 46.5% P valor for
      heterogeneity=0.113 and effect size=-0.60) when compared to group control. In
      conclusion, resistance training alone reduces systolic and diastolic blood
      pressure in prehypertensive and hypertensive subjects. The RCTs studies that
      investigated the effects of resistance training alone in prehypertensive and
      hypertensive patients support the recommendation of resistance training as a tool
      for management of systemic hypertension.

PMID- 28769101
TI  - Allostimulatory capacity of conditionally immortalized proximal tubule cell lines
      for bioartificial kidney application.
AB  - Novel renal replacement therapies, such as a bioartificial kidney (BAK), are
      needed to improve current hemodialysis treatment of end-stage renal disease
      (ESRD) patients. As BAK applications may reveal safety concerns, we assessed the
      alloimmunization and related safety aspects of readily available conditionally
      immortalized human proximal tubule epithelial cell (ciPTEC) lines to be used in
      BAK. Two ciPTEC lines, originally derived from urine and kidney tissue, were
      characterized for the expression and secretion of relevant molecules involved in
      alloimmunization and inflammatory responses, such as HLA class-I, HLA-DR, CD40,
      CD80, CD86, as wells as soluble HLA class I and proinflammatory cytokines (IL-6,
      IL-8 and TNF-alpha). A lack of direct immunogenic effect of ciPTEC was shown in
      co-culture experiments with peripheral blood mononuclear cells (PBMC), after
      appropriate stimulation of ciPTEC. Tight epithelial cell monolayer formation on
      polyethersulfone flat membranes was confirmed by zonula occludens-1 (ZO-1)
      expression in the ciPTEC tight junctions, and by restricted inulin-FITC
      diffusion. Co-culture with (activated) PBMC did not jeopardize the
      transepithelial barrier function of ciPTEC. In conclusion, the absence of
      allostimulatory effects and the stability of ciPTEC monolayers show that these
      unique cells could represent a safe option for BAK engineering application.

PMID- 28769102
TI  - Relaxation Oscillations and Ultrafast Emission Pulses in a Disordered Expanding
      Polariton Condensate.
AB  - Semiconductor microcavities are often influenced by structural imperfections,
      which can disturb the flow and dynamics of exciton-polariton condensates.
      Additionally, in exciton-polariton condensates there is a variety of dynamical
      scenarios and instabilities, owing to the properties of the incoherent excitonic
      reservoir. We investigate the dynamics of an exciton-polariton condensate which
      emerges in semiconductor microcavity subject to disorder, which determines its
      spatial and temporal behaviour. Our experimental data revealed complex burst-like
      time evolution under non-resonant optical pulsed excitation. The temporal
      patterns of the condensate emission result from the intrinsic disorder and are
      driven by properties of the excitonic reservoir, which decay in time much slower
      with respect to the polariton condensate lifetime. This feature entails a
      relaxation oscillation in polariton condensate formation, resulting in ultrafast
      emission pulses of coherent polariton field. The experimental data can be well
      reproduced by numerical simulations, where the condensate is coupled to the
      excitonic reservoir described by a set of rate equations. Theory suggests the
      existence of slow reservoir temporarily emptied by stimulated scattering to the
      condensate, generating ultrashort pulses of the condensate emission.

PMID- 28769103
TI  - Flower-Like Internal Emission Distribution of LEDs with Monolithic Integration of
      InGaN-based Quantum Wells Emitting Narrow Blue, Green, and Red Spectra.
AB  - We report a phosphor-free white light-emitting diodes (LED) realized by the
      monolithic integration of In0.18Ga0.82N/GaN (438 nm, blue), In0.26Ga0.74N/GaN
      (513 nm, green), and In0.45Ga0.55N/In0.13Ga0.87N (602 nm, red) quantum wells
      (QWs) as an active medium. The QWs corresponding to blue and green light were
      grown using a conventional growth mode. For the red spectral emission, five
      stacked In0.45Ga0.55N/In0.13Ga0.87N QWs were realized by the so-called Ga-flow
      interruption (Ga-FI) technique, wherein the Ga supply was periodically
      interrupted during the deposition of In0.3Ga0.7N to form an In0.45Ga0.55N well.
      The vertical and lateral distributions of the three different light emissions
      were investigated by fluorescence microscope (FM) images. The FM image measured
      at a focal point in the middle of the n-GaN cladding layer for the red-emitting
      LED shows that light emissions with flower-like patterns with six petals are
      periodically observed. The chromaticity coordinates of the electroluminescence
      spectrum for the white LEDs at an injection current of 80 mA are measured to be
      (0.316, 0.312), which is close to ideal white light. In contrast with phosphor
      free white-light-emitting devices based on nanostructures, our white light device
      exhibits a mixture of three independent wavelengths by monolithically grown InGaN
      based QWs, thus demonstrating a more facile technique to obtain white LEDs.

PMID- 28769104
TI  - Stretching Micro Metal Particles into Uniformly Dispersed and Sized Nanoparticles
      in Polymer.
AB  - There is a longstanding challenge to disperse metal nanoparticles uniformly in
      bulk polymers for widespread applications. Conventional scale-down techniques
      often are only able to shrink larger elements (such as microparticles and
      microfibers) into micro/nano-elements (i.e. nanoparticles and nanofibers) without
      much altering their relative spatial and size distributions. Here we show an
      unusual phenomenon that tin (Sn) microparticles with both poor size distribution
      and spatial dispersion were stretched into uniformly dispersed and sized Sn
      nanoparticles in polyethersulfone (PES) through a stack and draw technique in
      thermal drawing. It is believed that the capillary instability plays a crucial
      role during thermal drawing. This novel, inexpensive, and scalable method
      overcomes the longstanding challenge to produce bulk polymer-metal nanocomposites
      (PMNCs) with a uniform dispersion of metallic nano-elements.

PMID- 28769105
TI  - Transcriptome profiling of mouse colonic eosinophils reveals a key role for
      eosinophils in the induction of s100a8 and s100a9 in mucosal healing.
AB  - Eosinophils are bone marrow-derived cells that have been largely implicated in
      Th2-associated diseases. Recent data highlights a key role for eosinophils in
      mucosal innate immune responses especially in the gastrointestinal (GI) tract,
      which is one of the largest eosinophil reservoirs in the body. Although
      eosinophils express and synthesize a plethora of proteins that can mediate their
      effector activities, the transcriptome signature of eosinophils in mucosal
      inflammation and subsequent repair has been considerably overlooked. We
      demonstrate that eosinophils are recruited to the colon in acute inflammatory
      stages where they promote intestinal inflammation and remain in substantial
      numbers throughout the mucosal healing process. Microarray analysis of primary
      colonic eosinophils that were sorted at distinct stages of mucosal inflammation
      and repair revealed dynamic regulation of colonic eosinophil mRNA expression. The
      clinically relevant genes s100a8 and s100a9 were strikingly increased in colonic
      eosinophils (up to 550-fold and 80-fold, respectively). Furthermore, local and
      systemic expression of s100a8 and s100a9 were nearly diminished in eosinophil
      deficient DeltadblGATA mice, and were re-constituted upon adoptive transfer of
      eosinophils. Taken together, these data may provide new insight into the
      involvement of eosinophils in colonic inflammation and repair, which may have
      diagnostic and therapeutic implications.

PMID- 28769106
TI  - Lipoxin A4 and its analog suppress inflammation by modulating HMGB1 translocation
      and expression in psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disease that affects 2-3% of the global
      population, and there is still no known possibility of a cure. Lipoxin A4 (LXA4),
      an endogenous lipoxygenase-derived eicosanoid mediator, has potent dual pro
      resolving and anti-inflammatory properties. BML-111 (5(S)-6(R)-7
      trihydroxyheptanoic acid methyl ester), a lipoxin receptor agonist, has been
      previously confirmed to be equivalent to LXA4 in the anti-inflammatory processes.
      High mobility group box 1 (HMGB1) serves as an inflammatory cytokine when
      secreted extracellularly in psoriatic lesions and is involved in the development
      of psoriasis. Therefore, we investigated the effects of LXA4 and BML-111 on the
      HMGB1 signaling cascade and inflammation in lipopolysaccharide (LPS)-induced
      keratinocytes and imiquimod (IMQ)-induced psoriasiform dermatitis in mice. In the
      present study, we found that treatment with BML-111 attenuated the development of
      IMQ-induced psoriasiform dermatitis. Furthermore, treatment with BML-111 and LXA4
      inhibited HMGB1 translocation from the nucleus to cytoplasm and downregulated the
      expression of toll-like receptor 4 (TLR4), receptor for advanced glycation end
      products (RAGE), p-ERK1/2, nuclear NF-kappaB p65, and proinflammatory cytokines
      in vivo and in vitro. Our findings indicate that LXA4 and its analog may be
      potential therapeutic candidates for psoriasis because of their ability to
      modulate the translocation and expression of HMGB1.

PMID- 28769107
TI  - Innate Immune Basis for Rift Valley Fever Susceptibility in Mouse Models.
AB  - Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals
      and in humans that range from moderate fever to fatal illness, suggesting that
      host immune responses are important determinants of the disease severity. We
      investigated the immune basis for the extreme susceptibility of MBT/Pas mice that
      die with mild to acute hepatitis by day 3 post-infection compared to more
      resistant BALB/cByJ mice that survive up to a week longer. Lower levels of
      neutrophils observed in the bone marrow and blood of infected MBT/Pas mice are
      unlikely to be causative of increased RVFV susceptibility as constitutive
      neutropenia in specific mutant mice did not change survival outcome. However,
      whereas MBT/Pas mice mounted an earlier inflammatory response accompanied by
      higher amounts of interferon (IFN)-alpha in the serum compared to BALB/cByJ mice,
      they failed to prevent high viral antigen load. Several immunological alterations
      were uncovered in infected MBT/Pas mice compared to BALB/cByJ mice, including low
      levels of leukocytes that expressed type I IFN receptor subunit 1 (IFNAR1) in the
      blood, spleen and liver, delayed leukocyte activation and decreased percentage of
      IFN-gamma-producing leukocytes in the blood. These observations are consistent
      with the complex mode of inheritance of RVFV susceptibility in genetic studies.

PMID- 28769108
TI  - Extrapolar climate reversal during the last deglaciation.
AB  - Large ocean-atmosphere and hydroclimate changes occurred during the last
      deglaciation, although the interplay between these changes remains ambiguous.
      Here, we present a speleothem-based high resolution record of Northern Hemisphere
      atmospheric temperature driven polar jet variability, which matches the Greenland
      ice core records for the most of the last glacial period, except during the last
      deglaciation. Our data, combined with data from across the globe, show a dramatic
      climate reversal during the last deglaciation, which we refer to as the
      Extrapolar Climate Reversal (ECR). This is the most prominent feature in most
      tropical and subtropical hydroclimate proxies. The initiation of the ECR
      coincides with the rapid rise in CO2, in part attributed to upwelling in the
      Southern Ocean and the near collapse of the Atlantic Meridional Overturning
      Circulation. We attribute the ECR to upwelling of cold deep waters from the
      Southern Ocean. This is supported by a variety of proxies showing the incursion
      of deep Southern Ocean waters into the tropics and subtropics. Regional climate
      variability across the extropolar regions during the interval previously referred
      to as the "Mystery Interval" can now be explained in the context of the ECR
      event.

PMID- 28769109
TI  - Metal oxide nanostructures by a simple hot water treatment.
AB  - Surfaces with metal oxide nanostructures have gained considerable interest in
      applications such as sensors, detectors, energy harvesting cells, and batteries.
      However, conventional fabrication techniques suffer from challenges that hinder
      wide and effective applications of such surfaces. Most of the metal oxide
      nanostructure synthesis methods are costly, complicated, non-scalable,
      environmentally hazardous, or applicable to only certain few materials.
      Therefore, it is crucial to develop a simple metal oxide nanostructure
      fabrication method that can overcome all these limitations and pave the way to
      the industrial application of such surfaces. Here, we demonstrate that a wide
      variety of metals can form metal oxide nanostructures on their surfaces after
      simply interacting with hot water. This method, what we call hot water treatment,
      offers the ability to grow metal oxide nanostructures on most of the metals in
      the periodic table, their compounds, or alloys by a one-step, scalable, low-cost,
      and eco-friendly process. In addition, our findings reveal that a "plugging"
      mechanism along with surface diffusion is critical in the formation of such
      nanostructures. This work is believed to be of importance especially for
      researchers working on the growth of metal oxide nanostructures and their
      application in functional devices.

PMID- 28769110
TI  - Bark and wood tissues of American elm exhibit distinct responses to Dutch elm
      disease.
AB  - Tolerance to Dutch elm disease (DED) has been linked to the rapid and/or high
      induction of disease-responsive genes after infection with the fungus Ophiostoma
      novo-ulmi. Although the fungal infection by O. novo-ulmi primarily takes places
      in xylem vessels, it is still unclear how xylem contributes to the defense
      against DED. Taking advantage of the easy separation of wood and bark tissues in
      young American elm saplings, here we show that most disease-responsive genes
      exhibited higher expression in wood compared to bark tissues after fungal
      infection. On the other hand, the stress-related phytohormones were generally
      more abundant in the bark compared to wood tissues. However, only endogenous
      levels of jasmonates (JAs), but not salicylic acid (SA) and abscisic acid (ABA)
      increased in the inoculated tissues. This, along with the upregulation of JA
      biosynthesis genes in inoculated bark and core tissues further suggest that
      phloem and xylem might contribute to the de novo biosynthesis of JA after fungal
      infection. The comparison between two tolerant elm varieties, 'Valley Forge' and
      'Princeton,' also indicated that tolerance against DED might be mediated by
      different mechanisms in the xylem. The present study sheds some light on the
      amplitude and kinetics of defense responses produced in the xylem and phloem in
      response to DED.

PMID- 28769111
TI  - Pain management: Opioids for RA: a clinical dilemma.

PMID- 28769112
TI  - Vasculitis: Mepolizumab for eosinophilic granulomatosis with polyangiitis.

PMID- 28769113
TI  - Spondyloarthritis: Reinforcing 'treat to target' for SpA.

PMID- 28769115
TI  - Rheumatoid arthritis: Regulating the osteoclast workforce.

PMID- 28769116
TI  - The Reverse Transcriptases Associated with CRISPR-Cas Systems.
AB  - CRISPR (clustered regularly interspaced short palindromic repeats) and associated
      proteins (Cas) act as adaptive immune systems in bacteria and archaea. Some
      CRISPR-Cas systems have been found to be associated with putative reverse
      transcriptases (RT), and an RT-Cas1 fusion associated with a type III-B system
      has been shown to acquire RNA spacers in vivo. Nevertheless, the origin and
      evolutionary relationships of these RTs and associated CRISPR-Cas systems remain
      largely unknown. We performed a comprehensive phylogenetic analysis of these RTs
      and associated Cas1 proteins, and classified their CRISPR-Cas modules. These
      systems were found predominantly in bacteria, and their presence in archaea may
      be due to a horizontal gene transfer event. These RTs cluster into 12 major
      clades essentially restricted to particular phyla, suggesting host-dependent
      functioning. The RTs and associated Cas1 proteins may have largely coevolved.
      They are, therefore, subject to the same selection pressures, which may have led
      to coadaptation within particular protein complexes. Furthermore, our results
      indicate that the association of an RT with a CRISPR-Cas system has occurred on
      multiple occasions during evolution.

PMID- 28769117
TI  - Species specific anaesthetics for fish anaesthesia and euthanasia.
AB  - There is a need to ensure that the care and welfare for fish maintained in the
      laboratory are to the highest standards. This extends to the use of anaesthetics
      for both scientific study, humane killing and euthanasia at end of life. An
      anaesthetic should not induce negative behaviours and fish should not seek to
      avoid the anaesthetic. Surprisingly little information is available to facilitate
      a humane choice of anaesthetic agent for fish despite over 100 years of use and
      the millions of fish currently held in thousands of laboratories worldwide. Using
      a chemotaxic choice chamber we found different species specific behavioural
      responses among four closely related fish species commonly held in the
      laboratory, exposed to three widely used anaesthetic agents. As previously found
      for zebrafish (Danio rerio), the use of MS-222 and benzocaine also appears to
      induce avoidance behaviours in medaka (Oryzias latipes); but etomidate could
      provide an alternative choice. Carp (Cyprinus carpio), although closely related
      to zebrafish showed avoidance behaviours to etomidate, but not benzocaine or MS
      222; and rainbow trout (Oncorhynchus mykiss) showed no avoidance to the three
      agents tested. We were unable to ascertain avoidance responses in fathead minnows
      (Pimephales promelas) and suggest different test paradigms are required for that
      species.

PMID- 28769118
TI  - Earliest expansion of animal husbandry beyond the Mediterranean zone in the sixth
      millennium BC.
AB  - Since their domestication in the Mediterranean zone of Southwest Asia in the
      eighth millennium BC, sheep, goats, pigs and cattle have been remarkably
      successful in colonizing a broad variety of environments. The initial steps in
      this process can be traced back to the dispersal of farming groups into the
      interior of the Balkans in the early sixth millennium BC, who were the first to
      introduce Mediterranean livestock beyond its natural climatic range. Here, we
      combine analysis of biomolecular and isotopic compositions of lipids preserved in
      prehistoric pottery with faunal analyses of taxonomic composition from the
      earliest farming sites in southeast Europe to reconstruct this pivotal event in
      the early history of animal husbandry. We observe a marked divergence between the
      (sub)Mediterranean and temperate regions of Southeast Europe, and in particular a
      significant increase of dairying in the biochemical record coupled with a shift
      to cattle and wild fauna at most sites north of the Balkan mountain range. The
      findings strongly suggest that dairying was crucial for the expansion of the
      earliest farming system beyond its native bioclimatic zone.

PMID- 28769114
TI  - Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and
      technical advances.
AB  - First described in the early 1980s, antiphospholipid syndrome (APS) is a unique
      form of acquired autoimmune thrombophilia in which patients present with clinical
      features of recurrent thrombosis and pregnancy morbidity and persistently test
      positive for the presence of antiphospholipid antibodies (aPL). At least one
      clinical (vascular thrombosis or pregnancy morbidity) and one lab-based (positive
      test result for lupus anticoagulant, anticardiolipin antibodies and/or anti-beta2
      glycoprotein 1 antibodies) criterion have to be met for a patient to be
      classified as having APS. However, the clinical spectrum of APS encompasses
      additional manifestations that can affect many organs and cannot be explained
      exclusively by patients being in a prothrombotic state; clinical manifestations
      not listed in the classification criteria (known as extra-criteria
      manifestations) include neurologic manifestations (chorea, myelitis and
      migraine), haematologic manifestations (thrombocytopenia and haemolytic anaemia),
      livedo reticularis, nephropathy and valvular heart disease. Increasingly,
      research interest has focused on the development of novel assays that might be
      more specific for APS than the current aPL tests. This Review focuses on the
      current classification criteria for APS, presenting the role of extra-criteria
      manifestations and lab-based tests. Diagnostic approaches to difficult cases,
      including so-called seronegative APS, are also discussed.

PMID- 28769119
TI  - A promising high-energy-density material.
AB  - High-energy density materials represent a significant class of advanced materials
      and have been the focus of energetic materials community. The main challenge in
      this field is to design and synthesize energetic compounds with a highest
      possible density and a maximum possible chemical stability. Here we show an
      energetic compound, [2,2'-bi(1,3,4-oxadiazole)]-5,5'-dinitramide, is synthesized
      through a two-step reaction from commercially available reagents. It exhibits a
      surprisingly high density (1.99 g cm-3 at 298 K), poor solubility in water and
      most organic solvents, decent thermal stability, a positive heat of formation and
      excellent detonation properties. The solid-state structural features of the
      synthesized compound are also investigated via X-ray diffraction and several
      theoretical techniques. The energetic and sensitivity properties of the explosive
      compound are similar to those of 2, 4, 6, 8, 10, 12
      (hexanitrohexaaza)cyclododecane (CL-20), and the developed compound shows a great
      promise for potential applications as a high-energy density material.High energy
      density materials are of interest, but density is the limiting factor for many
      organic compounds. Here the authors show the formation of a high density
      energetic compound from a two-step reaction between commercially available
      compounds that exhibit good heat thermal stability and detonation properties.

PMID- 28769120
TI  - Interferon-gamma released from omental adipose tissue of insulin-resistant humans
      alters adipocyte phenotype and impairs response to insulin and adiponectin
      release.
AB  - BACKGROUND: Inflammatory factors derived from adipose tissue have been implicated
      in mediating insulin resistance in obesity. We sought to identify these using
      explanted human adipose tissue exposed to innate and adaptive immune stimuli.
      METHODS: Subcutaneous and omental adipose tissue from obese, insulin-resistant
      donors was cultured in the presence of macrophage and T-cell stimuli, and the
      conditioned medium tested for its ability to inhibit insulin-stimulated glucose
      uptake into human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. The nature of
      the inhibitory factor in conditioned medium was characterized physicochemically,
      inferred by gene microarray analysis and confirmed by antibody neutralization.
      RESULTS: Conditioned medium from omental adipose tissue exposed to a combination
      of macrophage- and T-cell stimuli inhibited insulin action and adiponectin
      secretion in SGBS adipocytes. This effect was associated with a pronounced change
      in adipocyte morphology, characterized by a decreased number of lipid droplets of
      increased size. The bioactivity of conditioned medium was abolished by trypsin
      treatment and had a molecular weight of 46 kDa by gel filtration. SGBS adipocytes
      exposed to a bioactive medium expressed multiple gene transcripts regulated by
      interferon-gamma (IFN-gamma). Recombinant human IFN-gamma recapitulated the
      effects of the bioactive medium and neutralizing antibody against IFN-gamma but
      not other candidate factors abrogated medium bioactivity. CONCLUSIONS: IFN-gamma
      released from inflamed omental adipose tissue may contribute to the metabolic
      abnormalities seen in human obesity.

PMID- 28769121
TI  - Acute effects of exercise on appetite, ad libitum energy intake and appetite
      regulatory hormones in lean and overweight/obese men and women.
AB  - BACKGROUND: Acute exercise does not elicit compensatory changes in appetite
      parameters in lean individuals; however, less is known about responses in
      overweight individuals. This study compared the acute effects of moderate
      intensity exercise on appetite, energy intake and appetite-regulatory hormones in
      lean and overweight/obese individuals. METHODS: Forty-seven healthy lean (n=22,
      11 females; mean (s.d.) 37.5 (15.2) years; 22.4 (1.5) kg m-2) and
      overweight/obese (n=25, 11 females; 45.0 (12.4) years, 29.2 (2.9) kg m-2)
      individuals completed two, 8 h trials (exercise and control). In the exercise
      trial, participants completed 60 min treadmill exercise (59 (4)% peak oxygen
      uptake) at 0-1 h and rested thereafter while participants rested throughout the
      control trial. Appetite ratings and concentrations of acylated ghrelin, peptide
      YY (PYY) and glucagon-like peptide-1 (GLP-1) were measured at predetermined
      intervals. Standardised meals were consumed at 1.5 and 4 h and an ad libitum
      buffet meal was provided at 7 h. RESULTS: Exercise suppressed appetite (95%
      confidence interval (CI) -3.1 to -0.5 mm, P=0.01), and elevated delta PYY (95% CI
      10 to 17 pg ml-1, P<0.001) and GLP-1 (95% CI 7 to 10 pmol l-1, P<0.001)
      concentrations. Delta acylated ghrelin concentrations (95% CI -5 to 3 pg ml-1,
      P=0.76) and ad libitum energy intake (95% CI -391 to 346 kJ, P=0.90) were similar
      between trials. Subjective and hormonal appetite parameters and ad libitum energy
      intake were similar between lean and overweight/obese individuals (P?0.27). The
      exercise-induced elevation in delta GLP-1 was greater in overweight/obese
      individuals (trial-by-group interaction P=0.01), whereas lean individuals
      exhibited a greater exercise-induced increase in delta PYY (trial-by-group
      interaction P<0.001). CONCLUSIONS: Acute moderate-intensity exercise transiently
      suppressed appetite and increased PYY and GLP-1 in the hours after exercise
      without stimulating compensatory changes in appetite in lean or overweight/obese
      individuals. These findings underscore the ability of exercise to induce a short
      term energy deficit without any compensatory effects on appetite regardless of
      weight status.

PMID- 28769122
TI  - Modulation of Gr1low monocyte subset impacts insulin sensitivity and weight gain
      upon high-fat diet in female mice.
AB  - BACKGROUND/OBJECTIVES: Blood monocytes are expanded during obesity. However, the
      differential contribution of monocyte subsets in obesity-related metabolic
      disorders remains unknown. The aim of the study was to define the role of the
      Gr1low monocyte subset upon high-fat diet (HFD). METHODS: We used transgenic
      female mouse models allowing the modulation of circulating Gr1low monocyte number
      (decreased number in CX3CR1-/- mice and increased number in CD11c-hBcl2 mice) and
      studied obesity upon HFD. RESULTS: We reported here that HFD induced monocytosis
      in mice, preferentially due to Gr1low monocyte expansion, and was associated with
      a specific upregulation of CD11c on that subset. Using mice models with altered
      Gr1low monocyte number, we found a striking correlation between Gr1low monocytes,
      bodyweight (BW) and insulin resistance (RT) status. Indeed, CX3CR1-/- female
      mice, with reduced Gr1low monocytes upon HFD, showed increased RT and a pro
      inflammatory profile of the adipose tissue (AT) despite a lower BW. Conversely,
      mice expressing the anti-apoptotic gene hBcl2 in CD11c-expressing cells have
      increased Gr1low monocytes, higher insulin sensitivity upon HFD and an anti
      inflammatory profile of the AT. Finally, increasing Gr1low monocytes in Gr1low
      defective CX3CR1-/- mice rescued BW loss in these mice. CONCLUSIONS: By using
      transgenic female mice and adoptive transfer experiments, we established the
      evidence for a correlation between Gr1low monocyte subset and weight gain and RT.
      Hence, this specific Gr1low monocyte subset could be used as a target for acting
      on AT inflammation and RT.

PMID- 28769123
TI  - Capecitabine, 5-fluorouracil and S-1 based regimens for previously untreated
      advanced oesophagogastric cancer: A network meta-analysis.
AB  - As evidence is inconsistent and based on either isolated Asian or Western
      studies, we conducted a network meta-analysis (NMA) to examine efficacy and
      safety of 5-FU (5-fluorouracil), capecitabine and S-1-based first-line treatment
      of advanced esophagogastric cancer in Asian and Western patients. Medline,
      EMBASE, CENTRAL and conferences ASCO and ESMO were searched up to January 2016
      for randomized-controlled-trials comparing 5-FU, capecitabine or S-1-based
      regimens with equal chemotherapy backbones. Direct and indirect data for overall
      survival (OS) and progression-free-survival (PFS) were combined on the Hazard
      Ratio (HR)-scale using random-effects NMA and calculated as combined HRs and
      95%credible intervals (95%CrI). Grade 1-2 and grade 3-4 adverse events were
      compared with pair-wise meta-analysis. Fifteen studies were identified including
      capecitabine (n = 945), 5-FU (n = 2,132) or S-1 (n = 1,636). No differences were
      found in respectively OS and PFS for capecitabine-based versus 5-FU-based
      regimens (HR = 0.89, 95%CrI = 0.76-1.04 and HR = 0.98, 95%CrI = 0.75-1.32), S-1
      based versus 5-FU-based regimens (HR = 0.92, 95%CrI = 0.82-1.04 and HR = 0.88,
      95%CrI = 0.70-1.11) and S-1-based versus capecitabine-based regimens (HR = 1.03,
      95%CrI = 0.87-1.22 and HR = 0.89, 95%CrI = 0.65-1.20). Effects were similar in
      Asian and Western subgroups. Toxicity profiles were different but a lower
      frequency of relevant adverse events was observed with S-1 In conclusion, as
      efficacy was similar, choosing fluoropyrimidines should be based on their
      individual toxicity profiles.

PMID- 28769125
TI  - Radiocarbon dating minute amounts of bone (3-60 mg) with ECHoMICADAS.
AB  - Because hard tissues can be radiocarbon dated, they are key to establishing the
      archaeological chronologies, palaeoenvironmental reconstructions and historical
      biogeographical processes of the last 50,000 years. The advent of accelerator
      mass spectrometers (AMS) has revolutionized the field of archaeology but routine
      AMS dating still requires 60-200 mg of bone, which far exceeds that of small
      vertebrates or remains which hold a patrimonial value (e.g. hominid remains or
      worked bone artefacts). Here, we present the first radiocarbon dates obtained
      from minute amounts of bone (3-60 mg) using a MIni CArbon DAting System
      (MICADAS). An optimized protocol allowed us to extract enough material to produce
      between 0.2 and 1.0 mg of carbon for graphite targets. Our approach was tested on
      known-age samples dating back to 40,000 BP, and served as proof of concept. The
      method was then applied to two archaeological sites where reliable dates were
      obtained from the single bones of small mammals. These results open the way for
      the routine dating of small or key bone samples.

PMID- 28769124
TI  - Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2
      Deficiency.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common kidney disease
      caused by mutations in PKD1 or PKD2. Metformin reduces cyst growth in mouse
      models of PKD1. However, metformin has not been studied in animal models of PKD2,
      and the cellular mechanism underlying its effectiveness is not entirely clear.
      This study investigated the effects of metformin on cyst formation in a zebrafish
      model of polycystin-2 deficiency resulting from morpholino knockdown of pkd2. We
      added metformin (2.5 to 20 mM) to the embryo media between 4 and 48 hours post
      fertilisation and observed pronephric cyst formation by using the wt1b promoter
      driven GFP signal in Tg(wt1b:GFP) pkd2 morphants. Metformin inhibited pronephric
      cyst formation by 42-61% compared with the untreated controls. Metformin also
      reduced the number of proliferating cells in the pronephric ducts, the degree of
      dorsal body curvature, and the infiltration of leukocytes surrounding the
      pronephros. Moreover, metformin treatment increased the phosphorylation of
      adenosine monophosphate-activated protein kinase (AMPK) and enhanced autophagy in
      the pronephros. Our data suggest that metformin reduces cyst formation through
      activation of the AMPK pathway and modulation of defective cellular events such
      as proliferation and autophagy. These results also imply that metformin could
      have therapeutic potential for ADPKD treatment.

PMID- 28769127
TI  - Lung Metastasectomy for Pulmonary Metastatic Breast Carcinoma.
AB  - Breast carcinoma with pulmonary metastasis can be treated locally or
      systemically. Following primary tumour resection patients with isolated,
      completely resectable pulmonary nodules and definite functional operability can
      be offered lung metastasis resection. Following metastasectomy a median survival
      of 32 to 96.6 months can be achieved with corresponding five-year survival rates
      between 30.8 and 54.4%. The procedure is associated with a mortality rate of 0 to
      3%. The most important independent prognostic factor for long-term survival is
      complete resection of all lung lesions. The configuration and pattern of
      metastasis as well as disease-free interval, hormone and HER2/neu receptor status
      also appear to influence prognosis, but are of lesser importance. Intrapulmonary
      recurrence of metastases may, after careful selection on a case-by-case basis,
      also be treated operatively. In some cases this is associated with a favourable
      long-term prognosis. Pulmonary metastasectomy should be the treatment of choice
      for selected patients with metastatic breast carcinoma.

PMID- 28769126
TI  - Initial Treatment of Patients with Primary Breast Cancer: Evidence,
      Controversies, Consensus: Spectrum of Opinion of German Specialists at the 15th
      International St. Gallen Breast Cancer Conference (Vienna 2017).
AB  - The St. Gallen International Consensus Conference on the treatment of patients
      with primary breast cancer has been held regularly (every second year in the last
      six years) for more than 30 years. This year, the findings of the International
      St. Gallen Consensus Panel and their implications for clinical practice were
      again discussed by a German working group of leading breast cancer specialists.
      Five of the breast cancer specialists from Germany were also members of this
      year's St. Gallen panel. A comparison between the St. Gallen recommendations and
      the annually updated treatment guidelines of the Gynecologic Oncology Group (AGO
      2017) and the S3-guideline agreed upon in 2017 is useful. The recommendations of
      the St. Gallen panel represent an international cross-section of opinions of
      experts from different countries and different disciplines, while the S3
      guideline and AGO guidelines are evidence-based. The motto of this year's 15th
      St. Gallen Conference was "Escalating and De-Escalating". The rationale behind
      this concept was to promote more individualized treatment and thereby reduce
      overtreatment as well as undertreatment.

PMID- 28769128
TI  - MR-Guided Focused Ultrasound in Fibroid Treatment - Results of the 3rd
      Radiological-Gynecological Expert Meeting.

PMID- 28769129
TI  - Uterine Artery Embolization (UAE) for Fibroid Treatment: Results of the 6th
      Radiological Gynecological Expert Meeting.

PMID- 28769130
TI  - Consensus Meetings Regarding Uterine Artery Embolization and Focused Ultrasound
      in Fibroid Treatment: an Analysis.

PMID- 28769131
TI  - Structure of the hydrophobic protein crambin determined directly from the
      anomalous scattering of sulphur.
AB  - The highly ordered crystal structure of crambin has been solved at 1.5 A
      resolution directly from the diffraction data of a native crystal at a wavelength
      remote from the sulphur absorption edge. The molecule has three disulphide
      bridges among its 46 amino acid residues, of which 46% are in helices and 17% are
      in a beta-sheet. Crambin is shown to be an amphipathic protein, inasmuch as its
      six charged groups are segregated from hydrophobic surface elements. Phasing
      methods used here will also apply elsewhere.

PMID- 28769132
TI  - Rheumatic and oncological diseases - common challenges.

PMID- 28769133
TI  - The prevalence of ANA antibodies, anticentromere antibodies, and anti-cyclic
      citrullinated peptide antibodies in patients with primary Sjogren's syndrome
      compared to patients with dryness symptoms without primary Sjogren's syndrome
      confirmation.
AB  - OBJECTIVES: Our study analyses the prevalence of ANA, anti-SS-A, anti-SS-B, and
      ACA and ACPA antibodies in patients with pSS and with dryness symptoms without
      pSS confirmation, and the association of ACPA and ACA antibodies with specific
      clinical symptoms. MATERIALS AND METHODS: 113 patients were divided into two
      groups: I - with diagnosed pSS (N = 75); and II - with dryness without pSS
      evidence (N = 38). Diagnostics: indirect immunofluorescence (IF; Hep-2 cell line)
      of antinuclear antibodies (ANA), anti-SS-A anti-SS-B antibodies determined with
      semi-quantitative method, autoantibody profile (14 antigens, ANA Profil 3
      EUROLINE); basic laboratory, ophthalmic examination tests, minor salivary gland
      biopsy with focus score (FS), joint and lung evaluation, and ESSDAI questionnaire
      (pSS activity). RESULTS: 88% of group I had ANA antibodies (1 : 320 titre), 5.3%
      at 1 : 160. Anti-SS-A antibodies were present in 88% of group I, including all
      ANA 1 : 160. Anti-SS-A antibodies positively correlated with greater and moderate
      activity of ESSDAI 5 (p = 0.046) and FS. The presence of SS-B antibodies
      significantly affected disease activity. ACPA present: group I - 13% (associated
      with higher arthritis incidence; p = 0.003); group II - 8%. ACA antibodies
      present in 4% of group I, but not in group II. No ACA association with
      interstitial lung changes (small ACA + group excludes full conclusions).
      CONCLUSIONS: ANA antibodies should also be considered in a titre of less than 1 :
      320, but the presence of anti-SS-A antibodies is still the most important
      immunological marker for pSS. Anti-SS-A antibodies correlate with higher disease
      activity (ESSDAI >= 5) and higher FS. The presence of the anti-SS-B antibody was
      significantly affected by higher activity of the disease. The incidence of
      arthritis was higher in patients with ACPA+ pSS compared to ACPA- (p = 0.003).
      There was no relationship between ACPA and arthritis in patients with dry-type
      syndrome without diagnosis of pSS.

PMID- 28769134
TI  - Rheumatology training in Poland vs. United Kingdom.
AB  - When evaluating the quality of Rheumatology specialty training, it can be useful
      to explore similarities and differences between countries. In this article we
      compare the training in the UK and Poland. The two training programmes are
      similar in length and in the competencies that must be achieved, although they do
      have significant differences in the way the training is structured. The UK-based
      system is more out-patient based, which can be advantageous, as after completion
      of training the doctor is more confident in treating common rheumatological
      problems. On the other hand, having exposure to paediatric rheumatology and
      orthopaedics like one has in Polish-based training, despite a short placement
      time, is definitely beneficial for the trainee in gaining all-round knowledge. In
      conclusion, each system has its merits and can be further enhanced by observing
      how junior doctors are sub-speciality trained in different countries.

PMID- 28769135
TI  - Fatigue - an underestimated symptom in psoriatic arthritis.
AB  - The nature of fatigue is very complex and involves physiological, psychological
      and social phenomena at the same time, and the mechanisms leading to occurrence
      and severity of fatigue are still poorly understood. The condition of chronic
      inflammation associated with psoriatic arthritis can be regarded as a potential
      factor affecting development of fatigue. Only a few studies so far have focused
      on the occurrence of fatigue in psoriatic arthritis. The problem of chronic
      fatigue is underestimated in everyday clinical practice. Identification and
      analysis of subjective fatigue components in each patient can provide an
      objective basis for optimal fatigue treatment in daily practice. This review
      presents a definition of chronic fatigue and describes mechanisms that may be
      associated with development of fatigue, highlighting the role of chronic
      inflammation, selected fatigue measurement methods and relations of fatigue
      occurrence with clinical aspects of psoriatic arthritis.

PMID- 28769136
TI  - Nail involvement in psoriatic arthritis.
AB  - Nail psoriasis is considered a significant psychological and social problem
      causing functional impairment in affected patients. Nail changes hamper their
      daily and occupational activities and contribute to a worse quality of life.
      Almost 50% of patients with psoriasis vulgaris and up to 80% of patients with
      psoriatic arthritis are afflicted with nail lesions. The important correlation
      between psoriatic arthritis and nail changes is well established - the presence
      of the latter is a strong predictor of the development of arthritis. There is a
      broad spectrum of nail dystrophies associated with psoriasis, ranging from the
      common pitting, subungual hyperkeratosis and loosening of the nail plate to less
      frequent discolouration and splinter haemorrhages. Some of these symptoms are
      also observed in other nail diseases, and further diagnostics should be
      performed. The assessment tools NAPSI (Nail Psoriasis Severity Index), mNAPSI
      (Modified Nail Psoriasis Severity Index), and PNSS (Psoriasis Nail Severity
      Score) are most commonly used to grade the severity of nail involvement in
      psoriasis and enable the evaluation of therapy effectiveness. The treatment of
      nail psoriasis is a major clinical challenge. It should be adjusted to the extent
      of dermal, articular and ungual lesions. Systemic therapies of psoriasis,
      especially biological agents, are most likely to be effective in treating nail
      psoriasis. However, as their use is limited in scope and safety, topical therapy
      remains a mainstay, and the combination of corticosteroids and vitamin D3
      analogues is considered to be most helpful.

PMID- 28769137
TI  - Is primary Sjogren's syndrome a risk factor for malignancies different from
      lymphomas? What does the literature highlight about it?
AB  - BACKGROUND: Primary Sjogren's syndrome (pSS) is a chronic systemic autoimmune
      disease with an elevated risk of developing lymphoproliferative malignancies
      (LM). Whether pSS is a risk factor or not for non-lymphoma malignancies (NLM) has
      been scarcely evaluated in the literature. Age is per se a risk factor for
      malignancies: patients over 70 years old have 4 times higher risk for cancers
      than adults. Even if the mean age of pSS onset usually is in the 4th and 5th
      decade, its onset in patients aged over 65 years (Elderly Onset pSS - EOpSS) is
      not uncommon. MATERIAL AND METHODS: To evaluate pSS as a risk factor for NLM we
      performed a systematic electronic search on PubMed in the period 2006-2016 to
      identify all the publications on this topic. The studies were eligible for
      inclusion if they reported specific Standardized Incidence Ratio (SIR) with 95%
      CI. Studies that did not report sufficient published and/or original data were
      excluded. RESULTS: Only 7 articles of 494 that we found in PubMed fulfilled the
      inclusion criterion. In the vast majority of these, SIR values were not
      statistically significant for NLM. The occurrence of NLM after LM was
      statistically significant in some studies and a NLM represented the most frequent
      cause of death. The possibility that NLM may represent a paraneoplastic syndrome
      seems much more frequent than LM, the risk of which increases with time after the
      diagnosis. Data regarding the neoplastic weight of EOpSS are mainly pointed out
      by case reports. CONCLUSIONS: Primary Sjogren's syndrome is not associated with
      an increased risk for NLM. However the possibility that NLM may appear after
      recovery from lymphoma should be carefully considered because it could be cause
      of the patient's death. Similarly the possibility that NLM may represent a
      paraneoplastic syndrome must be highlighted. The relationship between EOpSS and
      SIRs for NLM should be deepened with studies on ad hoc cohorts.

PMID- 28769138
TI  - Retroperitoneal fibrosis - a report of five cases.
AB  - Retroperitoneal fibrosis (RPF) is a rare disease, characterized by inflammation
      and deposition of fibrotic tissue in the vicinity of the abdominal aorta and
      iliac arteries. We present a report of five patients admitted to our department
      between January 2014 and February 2017, diagnosed with RPF. Abdominal pain was
      the most common presenting symptom; however, in one patient, RPF was identified
      accidentally in routinely performed ultrasonography. In 4 cases, corticosteroids
      (CS) in combination with azathioprine were applied as first-line therapy, whereas
      one patient was treated with intravenous methylprednisolone pulses followed by
      oral CS. In this paper, clinical features as well as laboratory and radiographic
      findings together with management and treatment outcomes in patients with RPF are
      discussed. Given the rarity of the condition, it seems important to report every
      single case of RPF to help establish its management algorithm.

PMID- 28769139
TI  - Three atypical manifestations of granulomatosis with polyangiitis: lateral
      medullary syndrome, anterior cheek mass and melting scleritis of eye.
AB  - Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) is a
      vasculitis with various organ involvement. There have been a few cases of CNS
      stroke and rare cases of lateral medullary infarction (LMI) as a manifestation of
      GPA. Also there have been reports of sinuses, nose and laryngeal masses
      mistakenly referred as carcinomas and subsequently GPA was diagnosed in their
      pathological reports. Another severe fulminant manifestation can be necrotizing
      scleritis leading to perforation of sclera. Therefore, here we present some rare
      and fulminant manifestations of GPA in 3 separate cases for further emphasis of
      the unusual manifestations of GPA that should always be kept in mind.

PMID- 28769140
TI  - Aortic aneurysm in a patient with syphilis-related spinal pain and paraplegia.
AB  - The tertiary stage of syphilis is nowadays extremely rare, showing predilection
      for the cardiovascular and nervous systems. A 57-year-old Caucasian man sought
      medical assistance due to back pain that evolved to paraplegia of the lower
      limbs. A thoracic CT scan demonstrated an important aneurysmatic lesion of the
      descending thoracic aorta causing erosion of the vertebral bodies and VDRL and
      FTA-abs positivity. Although rare, syphilitic aortitis, the hallmark of
      cardiovascular syphilis, should be considered in the differential diagnosis in
      patients with thoracic aneurysm when in the absence of classic risk factors for
      atherosclerosis, especially in cases that progress with erosion of vertebral
      bodies.

PMID- 28769142
TI  - Child Home Care Allowance and the Transition to Second- and Third-Order Births in
      Finland.
AB  - Using register data from the Finnish Census Panel, this paper studies the
      relationship between the use of the child home care allowance and second and
      third births among women aged 20-44 in Finland during the period 1992-2007.
      Discrete-time event-history analysis is applied to examine (i) whether women
      taking up the child home care allowance while their previous child was under the
      age of 3 have a higher risk to proceed to subsequent childbearing, (ii) whether
      these women proceed to a further birth more quickly, and (iii) whether the risk
      to proceed to a subsequent birth is related to educational level. The results
      show that women using the allowance have a higher risk of having a second and a
      third birth than women not using it. The risk of having a second birth is higher
      than that of having a third birth. Also, women using the allowance get their
      subsequent child sooner than women not using the allowance. No large educational
      differences in the effect of allowance use are found for second or third births.

PMID- 28769141
TI  - Treatment of Bisphenol A-Containing Effluents from Aerobic Granular Sludge
      Reactors with the Use of Microfiltration and Ultrafiltration Ceramic Membranes.
AB  - This study investigated the use of ceramic membranes to remove total suspended
      solids (TSS), organics (expressed by chemical oxygen demand, COD), and bisphenol
      A (BPA) via microfiltration (MF, pore size 0.45 MUm) and ultrafiltration (UF,
      cutoff 150 kDa) in post-treatment of effluents from aerobic granular sludge
      reactors (GSBRs). The efficiency of removal of COD, BPA, and TSS in MF was
      similar to that in UF; however, it was achieved at a lower pressure, which
      reduces energy consumption during the filtration process. Despite the similar
      quality of the permeates in MF and UF, the permeate flux averaged almost 20%
      higher in UF than in MF. The rejection coefficients were 77-82% for COD and 48
      100% for BPA. In both MF and UF, TSS were totally removed. In the integrated
      system of aerobic granular sludge reactor and membrane installation, total
      removal of COD was 92-95% and that of BPA was above 98%, independently of the
      membrane technique. The high efficiency of BPA removal in MF and UF, despite pore
      sizes in the MF and UF membranes larger than the BPA molecules, suggests that
      some part of the BPA was first bound by particulate organic matter in the
      biologically treated wastewater before this sorbed form was removed by the
      membranes. Furthermore, the high removal of COD and BPA, even in MF, was
      attributed to adsorption on the membranes, in addition to sieve retention.

PMID- 28769144
TI  - Fertility Intention, Son Preference, and Second Childbirth: Survey Findings from
      Shaanxi Province of China.
AB  - China is characterized by a low fertility intention, a strong preference for
      sons, as well as a stringent birth control policy. In this study, we used data
      from a Fertility Intention and Behavior Survey of 2101 questionnaires conducted
      in 2013 in Shaanxi Province of northwestern China, and event history analysis
      methods to examine the effect of fertility intention and preference for sons on
      the probability of having a second child. The results not only validate the
      correlation of fertility intention with having a second child empirically, even
      in the low fertility intention and stringent birth control context of China, but
      also show that women with a preference for sons were less likely to have a second
      child. Women with son preference turn to sex-selective abortion to ensure that
      their first child is a son, thus reducing the likelihood of a second child and
      decreasing the fertility rate. Our findings also shed light on China's potential
      fertility policy adjustment.

PMID- 28769143
TI  - Zonulin: A Potential Marker of Intestine Injury in Newborns.
AB  - INTRODUCTION: Zonulin (ZO), a new diagnostic biomarker of intestinal
      permeability, was tested in newborns presenting symptoms of infection and/or
      inflammation of the gut or being at risk of intestinal pathology. MATERIAL AND
      METHODS: Serum ZO was assessed in 81 newborns diagnosed with sepsis, necrotizing
      enterocolitis (NEC), rotavirus infection, and gastroschisis, also in extremely
      low gestational age babies, and in controls (healthy newborns). ZO concentration
      was compared to C-reactive protein (CRP) and procalcitonin (PCT) values,
      leucocyte and platelet count, basic demographic data, and the value of the
      Neonatal Therapeutic Intervention Scoring System (NTISS). RESULTS: Median values
      of ZO were markedly higher in groups with rotavirus infection and gastroschisis
      (36.0 (1-3Q: 26.0-43.2) and 20.3 (1-3Q: 17.7-28.2) ng/ml, resp.) versus controls
      (3.5 (1-3Q: 2.7-4.8) ng/ml). Its concentration in the NEC group was twice as high
      as in controls but did not reach statistical significance. ZO levels were not
      related to NTISS, CRP, and PCT. CONCLUSIONS: Zonulin is a promising biomarker of
      intestinal condition, markedly elevated in rotavirus infections. Its role in
      defining the severity of necrotizing enterocolitis and the risk for perforation
      is not well described and needs further evaluation. An increase in zonulin may
      not be parallel to the release of inflammatory markers, and low CRP should not
      exclude an injury to neonatal intestine.

PMID- 28769145
TI  - Assessing How Participators Combine Acts in Their "Political Tool Kits": A Person
      Centered Measurement Approach for Analyzing Citizen Participation.
AB  - Scholars have recognized that a recent increase in the ways citizens participate
      beyond the electoral arena may be a promising avenue of renewal for citizen
      participation. In this article we test the theory that different kinds of
      citizenship norms motivate some citizens to specialize in electoral-oriented
      activities (e.g. voting), while others specialize in non-institutionalized
      activities (e.g. protest). The latent class analysis of data from the U.S.
      Citizen, Involvement and Democracy Survey (2005) in the current study assesses
      how actors combine a variety of acts in their "political tool kits" of
      participation, and facilitates a comparison to prior findings that analyze single
      political behaviors. Results indicate a participatory type that specializes in
      non-institutionalized acts, but the group's high probability of voting does not
      align with the expectations in the literature. An electoral-oriented specialist
      type is not identified; instead, the findings show that a majority of the
      population is best characterized as disengaged, while a small group of all-around
      activists embrace all possible opportunities for political action. The actor
      centered theoretical and measurement approach in this study identifies caveats to
      the theory that changing citizenship norms are leading to civic and political
      renewal. We discuss the implications of these findings for measuring different
      aspects of democratic (dis)engagement and participatory (in)equality.

PMID- 28769146
TI  - What Does a Swiss Franc Mortgage Cost? The Tale of Polish Trust for Foreign
      Currency Denominated Mortgages: Implications for Well-Being and Health.
AB  - It is commonly agreed that excessive household financial debts are detrimental to
      psychological and physical health. Research also demonstrates that housing
      instability, mortgage indebtedness and mortgage foreclosure negatively influence
      subjective well-being. In Poland at the beginning of 2015, homeowners with Swiss
      franc denominated mortgages suffered from an abrupt swing in the Swiss
      franc/Polish zloty (CHF/PLN) exchange rate, which resulted in considerable
      increase in the local currency value of their mortgages. These adverse financial
      circumstances were hypothesised to affect not only household finance but also
      negatively affect the psychological well-being and physical health of peoples.
      The 2013 and 2015 waves of the Polish representative household panel 'Social
      Diagnosis' were used to examine impact of the abrupt change in the CHF/PLN
      exchange rate in Jan. 2015 on well-being and health. Causal inference was
      investigated using a difference-in-differences matching estimator. Results showed
      that although impact of Swiss franc appreciation on the mortgage related
      financial burden was considerable, it did not affect well-being or health
      outcomes. Any manifestation of adverse effects was absent in the short term,
      which does not however preclude their long term existence.

PMID- 28769147
TI  - Applications of the Capability Approach in the Health Field: A Literature Review.
AB  - The primary aims of this review are to document capability applications in the
      health field and to explore the objectives and decision-rules of studies
      measuring capability more broadly. Relevant studies are identified using a
      literature search strategy known as "comprehensive pearl growing". All studies
      with a primary focus on health are assessed individually, whilst a summary
      narrative analysis of the full review examines the objectives of capability
      studies. Four distinct groups in the health field are identified in the review:
      (1) physical activity and diet; (2) patient empowerment; (3) multidimensional
      poverty and (4) assessments of health and social care interventions. Different
      approaches to applying mixed methods, selecting capability dimensions and
      weighting capabilities are found across studies. There is a noticeable non
      reliance on health status as a sole indicator of capability in health. In terms
      of objectives of studies measuring capability, although there is a lack of
      consistency, an objective related to sufficiency of capabilities appeared most
      often in the studies found in this review. Even though one of the appeals of the
      capability perspective is its underspecified nature, this review highlights the
      challenge of finding a coherent alternative to more established approaches of
      evaluation.

PMID- 28769149
TI  - MEDICAL JOURNAL ARMED FORCES INDIA : A GOLDEN JUBILEE RETROSPECT.

PMID- 28769150
TI  - HIV INFECTION AND OBSTETRIC PRACTICE.

PMID- 28769151
TI  - RESURGENCE OF MT MALARIA AMONGST TROOPS SERVING IN THE NORTH EAST.
AB  - Cases of MT malaria amongst troops serving in the North East are on the increase.
      Study of the malaria morbidity and mortality data of the past five years covering
      a population of about 1.65 lakhs revealed that there is a definite resurgence of
      malaria from an incidence of 0.39 per thousand in 1989 to 0.54 per thousand in
      1992. Death due to malaria is a cause for concern especially since most of the
      troops are on chemoprophylaxis. A more realistic epidemiological approach to
      malaria control would be required to contain malaria.

PMID- 28769152
TI  - BONE RESPONSE TO STAINLESS STEEL AND TITANIUM BONE PLATES: An Experimental Study
      On Animals.
AB  - Various types of metallic implants have been used in the form of screws, bone
      plates and compression plates to achieve rigid internal fixation. In the present
      study, bone response to imported titanium bone plates and indigenously
      manufactured stainless steel bone plates, has been evaluated in dogs.

PMID- 28769148
TI  - Healthcare Systems in Comparative Perspective: Classification, Convergence,
      Institutions, Inequalities, and Five Missed Turns.
AB  - This essay reviews and evaluates recent comparative social science scholarship on
      healthcare systems. We focus on four of the strongest themes in current research:
      (1) the development of typologies of healthcare systems, (2) assessment of
      convergence among healthcare systems, (3) problematization of the shifting
      boundaries of healthcare systems, and (4) the relationship between healthcare
      systems and social inequalities. Our discussion seeks to highlight the central
      debates that animate current scholarship and identify unresolved questions and
      new opportunities for research. We also identify five currents in contemporary
      sociology that have not been incorporated as deeply as they might into research
      on healthcare systems. These five "missed turns" include an emphasis on social
      relations, culture, postnational theory, institutions, and causal mechanisms. We
      conclude by highlighting some key challenges for comparative research on
      healthcare systems.

PMID- 28769153
TI  - IS EARLY AMBULATION SAFE IN VIRAL HEPATITIS?
AB  - To derermine if early ambulation was safe in acute viral hepatitis (AVH), 202
      patients of uncomplicated AVH were prospectively randomised into two group. Group
      A (n=100) received conventional treatment with bed rest while group B (n=102)
      patients were ambulated as soon as their clinical symptoms abated and progressive
      clinical and biochemical recovery was noted. While mean recovery time in two
      groups was not significantlly different (28.8 vs 29.7 days), bed rest period in
      group B was significantly less (28.8 vs 8.6 days). Natural history of the AVH,
      clinical and biochemical findings and relapse rate over a follow up period of 14
      to 16 months, were no different in the two groups. None of the patients developed
      chronic hepatitis. Early ambulation is there fore safe in uncomplicated AVH and
      can lead to enormous saving of manhours and hospital resources.

PMID- 28769154
TI  - COLOUR DOPPLER ECHOCARDIOGRAPHY IN THE MANAGEMENT OF CONGENITAL HEART DISEASE.
AB  - Twenty patients with various forms of congenital heart disease admitted to Army
      Hospital Delhi Cantt were studied. After detailed clinical examination and
      routine investigations they were subjected to two dimensional and subsequently
      colour Doppler echocardiography. Two patients were operated on the data obtained
      by echocardiographi. studies only. Seven patients required preoperative
      catheterisation in addition to echographic examination. The operative procedures
      confirmed the lesions delineated on colour Doppler echocardiography. Three
      patients are on echocardiographic review and remaining seven are awaiting surgery
      to further confirm the diagnosis offered on colour Doppler echo. One pateint of
      complex lesion died before detailed evaluation could be carried out. Thus colour
      Doppler echocardiography, though considered highly accurate and non invasive
      investigation for assessment of congenital heart disease is still in the stage of
      infancy in paediatric set up and requires a high degree of expertise before it
      can replace preoperative catheterisation in majority of cases.

PMID- 28769155
TI  - ROLE OF CT SCAN IN PARTIAL SEIZURES IN CHILDREN.
AB  - 50 consecutive cases of partial seizures hospitalised over a period of 2 years,
      were studied. CT Scans were done once at presentation and thereafter cases were
      followed up with repeat CT scans to evaluate treatment response wherever a
      treatable cause was found. CT scan diagnosis was correlated with clinical signs
      and other baseline investigations including an EEG. CT scan abnormality was
      detected in 66% cases. Single or multiple tuberculomas were noted in 24% cases,
      cortical atrophy in 14% cases, focal calcification in 10%, haemorrhage in 3% and
      subdural effusions in 2%. With positive clinical signs, 81% of CT scans were
      abnormal. 20% of patients with partial seizures having no clinical signs and
      normal base line investigations including an EEG, had a CT scan abnormality
      mainly a tuberculoma.

PMID- 28769156
TI  - DIAGNOSTIC DILEMMAS IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA.
AB  - Clinical and hematological parameters in six cases of paroxysmal nocturnal
      hemoglobinuria (PNH) are presented. The mean delay in diagnosis after onset of
      symptoms was 3.7 years. Initial diagnoses considered were: (a) hematuria; (b)
      iron-deficiency; hemolytic; megaloblastic or refractory anemia and (c)
      myelodysplastic syndrome. Clinical features included; reddish urine (5/6),
      unexplained abdominal pain (4/6) and pallor (6/6). Laboratory investigations
      showed anemia (6/6), leucopenia (3/6), thrombocytopenia (3/6), unconjugated
      hyperbilirubinemia at some stage (6/6), and bone marrow erythroid hyperplasia
      (6/6). Complications encountered were (a) gall stones needing cholecystectomy,
      hemosiderosis and proximal tubular acidosis in 1 case, (b) disseminated
      tuberculosis in 1 case and (c) abortion with congestive cardiac failure in one.
      PNH may present with atypical features and tests for hemosiderinuria, sucrose
      lysis test and HAM's test are required to establish the diagnosis.

PMID- 28769157
TI  - OUR EXPERIENCE OF IOL IMPLANTATION IN PAEDIATRIC AGE GROUP.
AB  - Forty eyes of 35 patients in paediatric age group suffering from
      congenital/traumatic cataracts were operated. Posterior chamber intra ocular lens
      (PC IOL) implantation was carried out and followed for four years. Twenty one
      eyes (52.5%) showed visual recovery of 6/18 or better. Forward thrust was the
      commonest per operative complication. Uveitis and pupillary distortion were the
      common post operative complications. PC IOL implantation appears to be safe and
      promising procedure.

PMID- 28769158
TI  - EMOTIONAL FACTORS IN DUODENAL ULCER.
AB  - Anxiety and depression levels in 25 duodenal ulcer patients were compared with
      equal numbers of age and sex matched normal controls, hospitalised patients with
      nonpsychosomatic medical illnesses and inpatients with neurosis. Sinha's anxiety
      scale and Hamilton's rating scale for depression were used to measure the levels
      of anxiety and depression respectively. Patients with duodenal ulcer were
      significantly more anxious and depressed as compared to normal subjects and
      patients with medical illnesses. Duodenal ulcer patients were significantly less
      anxious and depressed as compared to neurotics. Therapeutic role of tricyclic
      antidepressants in management of duodenal ulcer is briefly discussed.

PMID- 28769159
TI  - DOSE RESPONSE RELATIONSHIP OF NEUROMUSCULAR BLOCKADE, INTUBATION CONDITIONS AND
      CARDIOVASCULAR CHANGES WITH CHANDONIUM IODIDE.
AB  - One hundred and forty ASA physical status I and II patients undergoing general or
      gynaecological surgery were the subjects of this study. Patients were randomly
      assigned into five groups receiving 100, 150, 180, 200 and 250 ug/kg I.V. of
      chandonium iodide after induction of general anaesthesia with thiopentone.
      Neuromuscular blockade was assessed clinically, as well as, with twitch
      response/train of four using myotest nerve stimulator. Increasing dosage of
      chandonium iodide decreased the time to onset of jaw relaxation and apnoea
      (p<0.01) and caused linear increase in the duration of neuromuscular blockade
      from 10.90 +/- 5.31 to 25.18 +/- 7.15 min (p<0.01) over the dosage rage of 100 to
      250 ug/kg. Intubation conditions also improved with increasing doses of
      chandonium iodide, so that, although intubation was possible in all the patients,
      grading of good intubation conditions were achieved in 64, 80, 88, 100 and 100%
      of patients in groups I to V respectively. 200 ug/kg of chandonium iodide
      produced ideal intubation conditions. Recovery to spontaneous ventilation was
      rapid and smooth, further facilitated with neuromuscular antagonists. Short
      lasting increase in heart rate and blood pressure was seen which was neither dose
      dependent nor outlasting the duration of neuromuscular blockade.

PMID- 28769160
TI  - PULMONARY EMBOLISM - AN ENIGMA.
AB  - Pulmonary embolism is considered a rare disease in India. The diagnosis is likely
      to be missed as its presentation is often enigmatic. Ten cases of pulmonary
      embolism are presented. Nine patients presented with acute pulmonary embolism,
      while one had chronic pulmonary emboli with cor pulmonale. The diagnosis was
      based on pulmonary angiography (1 case), lung perfusion/ventilation scan (2
      cases), autopsy (2 cases) and characteristic ECG, X-ray chest and clinical
      features (5 cases). The initial diagnosis was often incorrect (7/10 cases).
      Common presenting clinical features were: sudden breathlessness (10/10),
      tachypnoea (10/10) and tachycardia (8/10); chest pain (3/10) was uncommon and
      hemoptysis was not seen in any patient. ECG revealed isolated sinus tachycardia
      in 2 cases, S1 Q3 T3 pattern in 2, and right axis with ST-T wave changes in 5
      patients. X-ray chest showed either an area of oligemia or non-specific opacities
      in 7 patients and was normal in three cases. Advances in specific diagnostic
      modalities coupled with heightened awareness should contribute to an early
      detection of pulmonary embolism, rarity of which may be more apparent than real.

PMID- 28769161
TI  - DIAGNOSIS AND MANAGEMENT OF SOFT-TISSUE SARCOMAS.
AB  - Soft-tissue sarcomas are locally aggressive tumours with a tendency to spread
      haematogenously, especially to the lungs. Most patients present without obvious
      metastases. Their management is dependent on an adequate incisional biopsy to
      assess the grade of the tumour. The biopsy incision must be carefully placed so
      as not to compromise subsequent radical excision. Of patients so treated, 20 to
      30% experience local recurrence within the first 3 years postoperatively. The use
      of adjuvant radiotherapy decreases the incidence of local recurrence to about
      15%. Patients with retroperitoneal sarcomas have a greater tendency to suffer
      recurrence, with disseminated disease throughout the abdomen. The overall 5-year
      survival rate is about 50%. Patients may, however, have persistent disease or
      develop metastases beyond the 5-year period. The optimal timing of radiation and
      chemotherapy remains unresolved, but multimodality treatment at least allows the
      advocation of limb-sparing procedures for patients with soft-tissue sarcomas.

PMID- 28769162
TI  - AWARENESS DURING SURGERY UNDER ANAESTHESIA (A Case Report).
AB  - A case of intra-operative awareness due to fault in anaesthetic apparatus is
      reported. This report highlights the importance of routine checking and periodic
      maintenance of anaesthetic apparatus to avoid such an occurrence.

PMID- 28769163
TI  - VIRAL ENCEPHALITIS PRESENTING AS CATATONIC SCHIZOPHRENIA (A Case Report).
AB  - A rare case of viral encephalitis in an 18 year old recruit who presented with
      signs of catatonic schizophrenia is reported.

PMID- 28769164
TI  - PARADUODENAL HERNIA (A Case Report).
AB  - A case of right paraduodenal hernia is reported. Embryogenesis and treatment of
      this rare type of internal hernia is discussed.

PMID- 28769165
TI  - WILSON'S DISEASE (A report of two cases).
AB  - Two cases of Wilson's disease are reported. First case presented with fulminant
      hepatic failure and had a fatal outcome. The second had an insiduous onset,
      neurological manifestations, and is progressing satisfactorily on zinc therapy.
      Problems in diagnosis and treatment are highlighted.

PMID- 28769166
TI  - PLEOMORPHIC LIPOMA (A Case Report).
AB  - A case of a pleomorphic lipoma in a 61 year old male is reported. This tumour is
      very rare and is usually seen in the head and neck region in the elderly. It is
      more often than not labelled malignant. The case is reported on account of its
      rarity and to highlight the unusual features which make it liable to be confused
      ns a malignant tumour.

PMID- 28769167
TI  - DISSEMINATED INTRAVASCULAR COAGULATION FOLLOWING MULTIPLE BEE STINGS (A Case
      Report).
AB  - Disseminated intravascular coagulation (DIC) as a toxic effect of multiple bee
      stings has not been described. A 28 year old male was bitten by a swarm of bees
      and was hospitalised twelve hours later with generalized bleeding manifestations.
      He died within three hours of hospitalisation due to uncontrolled bleeding, in
      spite of blood transfusions and supportive therapy. Detailed laboratory
      investigations and postmortem histopathological examination showed diagnostic
      evidence of DIC.

PMID- 28769168
TI  - GAS POISONING WITH FREON-12 (A Report of Three Cases).
AB  - Three pauents of accidental gas poisoning with Freon-12 are reported. Presenting
      features were transient loss of consciousness, bradycardia, hypotension and
      anaesthesia. All patients made a rapid and uneventful recovery without any
      residual effects.

PMID- 28769169
TI  - PULMONARY MICROLITHIASIS (An Autopsy Study).
AB  - A case of pulmonary microlithiasis of unknown aetiology is described. Patient
      died of acute respiratory distress with cyanosis. Autopsy study did not reveal
      any of the known associated syndromes.

PMID- 28769170
TI  - KETAMINE ANAESTHESIA FOR GYNAECOLOGICAL LAPAROSCOPY : OXYMETRIC AND CAPNOGRAPHIC
      APPRAISAL.

PMID- 28769172
TI  - COMPUTERISATION OF MEDICAL STORE INDENTS : A PILOT STUDY.

PMID- 28769171
TI  - KETAMINE ANAESTHESIA FOR GYNAECOLOGICAL LAPAROSCOPY : OXYMETRIC AND CAPNOGRAPHIC
      APPRAISAL: Author's Reply.

PMID- 28769173
TI  - NON SURGICAL OPTIONS IN "SURGICAL" JAUNDICE.

PMID- 28769174
TI  - BIOLOGY OF NEUROCYSTICERCOSIS - PARASITE RELATED FACTORS MODULATING HOST
      RESPONSE.
AB  - Neurocysticercosis, caused by infestation of the nervous system by the larval
      form of Taenia solium, continues to baffle the neurologist, because of varied
      clinical manifestations. A large body of the literature related to this disease
      is clinically oriented, enough attention has not been given to parasite related
      factors modulating the host response. Using immunohistochemical techniques, three
      features related to the biology of the Cysticercus cellulosa e were studied.
      Firstly, to the question as to which part of the worm is recognised by the host
      immune system, the surface glycoprotein is found to be immunolabelled by the CSF
      from patients of neurocysticercosis. This surface protein is depleted following
      specific antihelmenthic therapy, thus accounting for a fall in anticysticercal
      antibosy level in the CSF. Secondly, the cysticercal cyst, by immunochemical and
      histochemical methods, is found to have "ACTH like" molecule in the body wall and
      has neurotransmitter and mitochondrial metabolic pathways similar to the host,
      facilitating the immune evasion and successful parasitisation. Finally,
      Cysticercus cellulosae is found to contain a "peptide" opening the blood brain
      barrier at the arteriolar level when injected into mice intravenously. Similar
      phenomenon may be functional in the patients as well, resulting in cerebral
      oedema, especially following praziquintel therapy.

PMID- 28769175
TI  - ADENOCARCINOMA STOMACH A REVIEW OF 168 CASES.
AB  - Medical records of 168 patients with gastric adenocarcinoma treated at Malignant
      Diseases Treatment Centre, Command Hospital (SC) Pune over a ten year period were
      analysed. Laparotomy was performed in 146 patients; in 82 patients a gastric
      resection was done, palliative gastrojejunostomy was done in 42 patients, while
      in 22 patients only a diagnostic biopsy was done. The resection was considered to
      be curative in 21 patients. Overall operative mortality was 12.3%. According to
      the international TNM Classification 16% patients were in Stage I, 13.7% in Stage
      II, 34.3% in Stage III and 35.8% in Stage IV. A significant correlation was found
      between five year survival rate and overall stage of disease as well as regional
      lymph node involvement (p < 0.001). Significantly better survival rates were seen
      in those who had curative resection as opposed to palliative resection (p <
      0.01). Overall survival rate at five years in our patients was 8.3% this poor
      outcome was probably related to the advanced stage of disease at presentation.

PMID- 28769176
TI  - EFFICACY OF SUCRALFATE IN PREVENTING GASTROINTESTINAL SIDE EFFECTS OF NSAIDs.
AB  - To find out the efficacy of sucralfate in preventing gastrointestinal side
      effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective,
      randomised single blind study was conducted from 1989 to 1992. Patients with
      osteoarthritis, rheumatoid arthritis and other long standing painful conditions,
      who were expected to receive NSAIDs for over three months, were recruited into
      the study. All medicines were discontinued for a period of 10-15 days prior to
      initial endoscopic assessment. NSAID therapy was started and the patients were
      randomised to receive either placebo (group A) or sucralfate (group B) in
      addition. Patient were reassessed clinically every week and an endoscopic
      examination was repeated after 6-8 weeks of follow-up. A total of 176 patients
      were studied in group A (n=91) and group B (n=85). At the end of 8 weeks
      gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and
      B respectively. Endoscopic assessment showed superficial lesions in 36.5% and
      18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B
      respectively. Thus in patients receiving chronic NSAID therapy, simultaneous
      administration of sucralfate reduces the incidence of superficial gastric lesions
      but has no significant effect on symptoms or ulcer formation.

PMID- 28769177
TI  - ROLE OF LEFT VENTRICULAR FUNCTION EVALUATION IN NON SPECIFIC ECG ABNORMALITY.
AB  - A total of 373 subjects [367 service persons and 6 civilians) with ECG
      abnormality were evaluated with maximal TMT exercise, 86 (23%) of them showing
      positivity. Subsequent assessment including radionuclide ventriculography and
      coronary arteriography wherever necessary revealed coronary artery disease in 31
      (8.3%). The remaining 55 were further evaluated by 2D and M-Mode echocardiography
      for exclusion of any other cardiac disease responsible for the ECG abnormality as
      well as for assessment of LV performance. Seven subjects showed minor structural
      cardiac anomalies - MVP in 5 and HOCM in 2. The remaining 48 showed no
      significant difference in the measurements of LV posterior wall and IV septal
      wall thickness, mitral septal separation, mitral valve excursion velocities, LV
      end-systolic/end-diastolic internal diameters and calculated percent fractional
      shortening, LV end-diastolic, end-systolic and stroke volumes as well as ejection
      fraction, on comparison with 20 age matched controls. These 48 service persons,
      thus evaluated were considered to have no organic heart disease or cardiac
      function impairment and were cleared for all strenuous duties including flying of
      sophisticated aircrafts or posting to high altitudes.

PMID- 28769178
TI  - LIPID PROFILE IN NORMAL HEALTHY CHILDREN.
AB  - One hundred and fifty healthy children in the age group of 0-12 years were
      studied to establish normal levels of lipid profile. They were divided into six
      equal groups viz., newborns, 0-1 year, 1-4 years, 4-7 years, 7-10 years and 10-12
      years. The mean values +/- SD for total cholesterol, HDL cholesterol, LDL
      cholesterol and triglycerides were 70 +/- 14.48 mg/dl, 35.1 +/- 8.04 mg/dl, 23.8
      +/- 10.62 mg/dl and 50.9 +/- 20.77 mg/dl respectively for male neonates and 71.8
      +/- 13.96 mg/dl, 34.6 +/- 6.55 mg/dl, 25.5 +/- 9.29 mg/dl and 57.2 +/- 18.57
      mg/dl respectively for female neonates. These values increased to 158.7 +/- 21.23
      mg/dl, 60.7 +/- 11.70 mg/dl, 80.3 +/- 19.26 mg/dl, 86.7 +/- 28.80 mg/dl in males
      and 161.6 +/- 23.09 mg/dl 66.7 +/- 8.75 mg/dl, 75.8 +/- 20.26 mg/dl and 93.2 +/-
      44.09 mg/dl in females respectively between 10-12 years of age, The various lipid
      fractions were at the lowest level at birth and increased significantly during
      first year of life, there after showing a much slower rise in levels. There was
      no significant difference in values between male and female children.

PMID- 28769179
TI  - ROLE OF EPIDURAL MEDICATION IN LUMBOSCIATIC SYNDROME.
AB  - Role of epidural medication through caudal route was studied in 109 patients
      having lumbago with or without sciatica to highlight the value of this mode of
      treatment which relieved symptoms in more than 70% of cases without
      hospitalisation and without being off work for long periods as in usual methods
      of conservative treatment.

PMID- 28769180
TI  - VIOLENT BEHAVIOUR IN PYSCHIATRIC INPATIENTS.
AB  - A study of violent behaviour among psychiatric inpatients in a large general
      hospital is presented. Over the study period of one year a total of 36 incidents
      of violence involving 26 patients were recorded. Schizophrenia was the most
      common diagnosis among assailants. Fellow patients were the main victims.
      Incidence of serious violence was low. Most incidents occurred in the night
      hours, from inmates of acute wards and mostly without any provocation.

PMID- 28769181
TI  - MIDDLE EAR RECONSTRUCTION - OUR EXPERIENCE.
AB  - A comparative study of ossicular reconstrution using four different graft
      material was carried out on 40 patients as a second stage procedure from July
      1989 to June 1991. The graft materials used were : aulologus ossicular bone
      graft, allogeneic ossicular bone graft, autologus cartilage and bio-compatible
      materials. All patients were observed for a period ranging from one to two years.
      Extrusion of ossicular graft was prevented by use of a lace of cartilage between
      the ossicular graft and neotympanic membrance. Satisfactory results were obtained
      with cartilage graft in 6%, allogeneic ossicles 70%, autologus ossicular graft
      80% and bio-compatible materials 33.3%.

PMID- 28769182
TI  - HAEMOPTYSIS - INDICATIONS FOR BRONCHOSCOPY.
AB  - Fifty patients who were taken up for bronchoscopy for evaluation of haemoptysis
      have been studied retrospectively in order to confirm specific diagnosis,
      identify the bleeding site and find the incidence of malignancy and other lesions
      in lower respiratory tract. We encountered over all 30% diagnostic yield.
      Malignancy was found in 4% of our patients and overall diagnostic yield was
      higher (35.7%) in patients of more than 40 years of age as compared to that
      (26.6%) in patients younger than 40 years of age. Criteria and indications of
      bronchoscopic examination in haemoptysis have been described.

PMID- 28769183
TI  - ACUTE RENAL FAILURE - CHANGING TRENDS.
AB  - A prospective study of 120 patients of acute renal failure was done at CH (EC)
      Calcutta to document the changing trends in the incidence and etiology of acute
      renal failure and to assess the prognostic factors. Mean age of patients was 33.7
      +/- 20.2 years. 75% had a medical risk factor. The etiological factors were
      volume depletion (13.3%), septicaemia (25.6%), falciparum malaria (16.6%), a
      transplant related renal failure (5.7%) and drugs (16.7%). Renal histology showed
      acute tubular necrosis to be the most common lesion (53.3%). In 13.3% patients
      who died with acute renal failure, associated infection and multisystem
      involvement was more common.

PMID- 28769184
TI  - BREAST-FEEDING AND PRIMARY MATERNAL HIV INFECTION : FURTHER EVIDENCE OF
      TRANSMISSION.

PMID- 28769185
TI  - PARAGONIMIASIS IN MANIPUR.

PMID- 28769186
TI  - RESOURCE MANAGEMENT INITIATIVE AND QUALITY - GETTING THE CLIMATE RIGHT.

PMID- 28769187
TI  - GUIDELINES FOR AUTOPSY IN HIV POSITIVE CASES.
AB  - Autopsy on a patient who had died as a consequence of acquired immune deficiency
      syndrome (AIDS) can be of great value in understanding the disease process. A
      potential risk to the prosector for acquiring the HIV exists, but if adequate
      preventive measures are undertaken, the risk is negligible. Indeed there is no
      documented evidence of a pathologist or an autopsy room attendant acquiring HIV
      infection while performing autopsy on a patient with AIDS. The procedures to be
      followed in the autopsy of the patient with AIDS are discussed.

PMID- 28769188
TI  - LAPAROSCOPIC SURGERY.
AB  - The speed of adoption and popularity of laparoscopic cholecystectomy is without
      precedence in modern surgical history. This has resulted in therapeutic and
      diagnostic laparoscopy being attempted in almost every field of surgery to
      substitute open surgical procedures. The list is endless. It will take time to
      evaluate the safety and advantages of many of these procedures as reports of
      controlled studies and long term follow up results are awaited. While certain
      procedures like gall bladder surgery and appendicectomy will establish their many
      fold advantages over open surgery, many other procedures like repair of hernias,
      radical resection of bowel for malignancy etc may fail to do so once the initial
      enthusiasm wanes away. Any way the concept of minimally invasive surgery is going
      to be a dominant factor in the surgery of this decade and one should prepare to
      face this fascinating challenge. Further developments in laparoscopic
      instruments, optical system and video imaging techniques will add to the progress
      and safety of laparoscopic surgical procedures in the days ahead.

PMID- 28769189
TI  - VEGETABLE FOREIGN BODY IN THE BRONCHUS IN A CHILD (A Case Report).
AB  - A case of vegetable foreign body in the bronchus in a child is presented. The
      foreign body was removed by rigid bronchoscopy, but post-operatively the child
      developed respiratory distress necessitating a tracheostomy. This case is
      illustrative of the problem inherent in the management of vegetable foreign
      bodies in the air passage in children. The relevant literature has been reviewed.

PMID- 28769190
TI  - METALLIC FOREIGN BODY IN LEFT MAIN BRONCHUS (A Case Report).
AB  - A child with accidental inhalation of a metallic foreign body into left main
      bronchus is reported. The foreign body was removed by rigid bronchoscopy. The
      problems in management are discussed and current literature reviewed.

PMID- 28769191
TI  - ANEURYSM OF SINUS OF VALSALVA DISSECTING INTO THE INTERVENTRICULAR SEPTUM -
      ECHOCARDIOGRAPHIC DIAGNOSIS (A Case Report).
AB  - Aneurysm of sinus of Valsalva dissecting into interventricular septum is a rare
      entity. We report one such case who was incidentally diagnosed by
      echocardiography to have this abnormality during evaluation of a clinically
      suspected isolated aortic regurgitation.

PMID- 28769192
TI  - ISOLATED LEVOCARDIA WITH SITUS INVERSUS (A Case Report).
AB  - A case of isolated levocardia with situs inversus is reported. The child had a
      normally formed spleen, which is uncommon in such cases.

PMID- 28769193
TI  - ENTEROLITHS PROXIMAL TO TUBERCULOUS ILEAL STRICTURES (A Report of 3 Cases).
AB  - Enteroliths proximal to tuberculous ileal strictures are an uncommon cause of
      recurrent or subacute intestinal obstruction and the radiopaque shadows cast by
      them give rise to a diagnostic dilemma. Three such cases are reported and the
      etio-pathology and diagnosis of intestinal calculi discussed.

PMID- 28769194
TI  - OSTEOMA CUTIS (A Case Report).
AB  - A case of osteoma cutis in a woman of 48 years is reported. The primary cutaneous
      ossification has a unique congenital and noninvasive nature. The histological
      features of the lesion are illustrated.

PMID- 28769195
TI  - CHOLECYSTECTOMY THROUGH A MINI-LAPAROTOMY A PRELIMINARY REPORT.
AB  - Cholecystectomy through a small subcostal incision (mini-lap cholecystectomy),
      has recently been introduced as an alternative to conventional cholecystectomy in
      an effort to reduce its attendant morbidity. A trial was conducted to assess the
      morbidity of cholecystectomy performed through a small subcostal incision.
      Eighteen consecutive patients posted for elective cholecystectomy were operated
      through such an incision. In 2 [11%], the incision had to be extended. The
      records of these patients were retrospectively compared with an equal number of
      consecutive cholecystectomies previously performed by the same surgeon through a
      conventional incision. There was no significant difference in the average
      operating time, incidence of wound infection or the number of post-operative
      complications between the conventional and the mini-laparotomy group. However,
      the number of doses of post operative analgesic required, the duration of post
      operative ileus, hospitalisation and convalescence needed was nearly halved. Thus
      mini-lap cholecystectomy has much lesser morbidity and is considered to be a safe
      and viable alternative to conventional cholecystectomy.

PMID- 28769196
TI  - PULMONARY LESIONS ASSOCIATED WITH BLEOMYCIN THERAPY IN MALIGNANCIES.
AB  - Pulmonary lesions in seven patients with malignancy who were treated with
      bleomycin were studied at autopsy. Six of them had symptoms of respiratory
      distress. The lesions showed a predilection for the lower lobe and subpleural
      zones. Diffuse alveolar damage progressing to interstitial pneumonitis at varying
      stages of evolution was observed in all cases. The changes included intra
      alveolar proteinaceous exudate, extensive interstitial fibrosis and frank
      epithelial dysplasia simulating metastatic nodules.

PMID- 28769197
TI  - CLINICO-EPIDEMIOLOGICAL ALGORITHM FOR PREDICTING SYSTEMIC ARTERIAL HYPERTENSION
      AT HIGH ALTITUDE THROUGH MATHEMATICAL MODELLING.
AB  - A population based hybrid design combining element of cohort and cross-sectional
      approach was used to develop a simple clinical algorithm to predict individual
      probability of developing hypertension (systolic BP > 140 mm Hg and/or diastolic
      BP > 90 mmHg). 3615 soldiers initially normotensive at the time of induction into
      high altitude, were studied by systematic random sampling. Multiple logistic
      regression analysis showed a high significant association between hypertension
      and age, body mass index (BMI), tobacco smoking and alcohol consumption. Using
      the constant/coefficient values obtained from the logistic model and the receiver
      operating characteristics (ROC) curve analysis, the following predictive rule was
      developed - To the age in years, add (BMIx 3.86); also add 5.53 if he is a
      smoker; and add 19.81 if he consumes alcohol. If the total exceeds 142, the
      individual is at high risk of developing hypertension. This algorithm carries a
      sensitivity of 68.2% and specificity of 78.5%.

PMID- 28769198
TI  - VARIABLE RATE IV INFUSION OF MORPHINE AND HAEMODYNAMIC RESPONSE TO LARYNGOSCOPY
      AND TRACHEAL INTUBATION.
AB  - Haemodynamic response to laryngoscopy and tracheal intubation was studied in two
      groups of 45 patients each. Group I patients received variable rate infusion of
      morphine for 30 minutes followed by intravenous (IV) bolus dose of diazepam.
      Group II patients received intramuscular morphine as preanaesthetic premedication
      and preinduction IV bolus dose of diazepam. The method of induction of GA was
      same in both the groups. Systolic and diastolic blood pressure (SBP and DBP) mean
      arterial pressure and pulse-rate were recorded at intubation and at different
      time intervals upto 10 minutes after intubation. In group I patients, there was
      no statistically significant increase in pulse-rate and SBP following intubation
      but transient significant increase in DBP. In group II patients, there was
      statistically significant increase in pulse-rate, SBP and DBP upto 3 minutes post
      intubation. Thus IV infusion of morphine in combination with IV bolus dose of
      diazepam proved more effective in attenuating haemodynamic response to tracheal
      intubation.

PMID- 28769199
TI  - IN VITRO COMPARATIVE ACTIVITY OF EIGHT ANTIPSEUDOMONAL AGENTS.
AB  - Five hundred and thirty strains of Pseudomonas aeruginosa isolated from indoor
      patients were tested against three chemical groups comprising eight antibiotics.
      High degree of resistant strains ranging from 38.0% to 61.8% were seen against
      carbenicillin, piperacillin and gentamicin. However amikacin, ciprofloxacin,
      ceftazidime, netilmicin and norfloxacin showed comparatively better activity with
      resistant strains ranging from 7.8% to 22.8%. A notably higher rate of resistance
      was seen in urinary isolates.

PMID- 28769200
TI  - RENAL TRANSPLANTATION - AN EARLY EXPERIENCE.
AB  - Renal transplant (RT) is now a therapy of choice for end stage renal disease
      (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date
      1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were
      in ESRD and 11 patients underwent renal transplantation at this hospital during
      the period Jan 91 - Dec 93. One patient expired after 18 months of
      transplantation due to infection. Early experience in screening patients for RT,
      use of immunosuppression, management of rejection episodes and protocol are
      presented with special emphasis on its relevance to the Armed Forces.

PMID- 28769201
TI  - SMOKING AND ULCERATIVE COLITIS - DOES NICOTINE HELP?

PMID- 28769202
TI  - CAN ASPIRIN PREVENT COLON CANCER?

PMID- 28769203
TI  - IMPORTANCE OF DONOR SELECTION IN RENAL TRANSPLANTATION.
AB  - Renal transplantation has become a treatment of choice for patients with end
      stage renal disease. A successful transplant is the result of a combination of
      several factors acting synergistically, such as the degree of HLA compatibility
      between donor and the recipient, pretransplant blood transfusions, the
      recipient's state of immunoreactivity and sensitization, immunosuppressive
      therapy given in post operative period etc. Donor selection appears to be the
      most critical factor for the long term success of the organ graft. In this brief
      review, some of the important parameters of donor selection in renal
      transplantation are highlighted.

PMID- 28769204
TI  - PERIPARTUM CARDIOMYOPATHY AND ANAESTHESIA (A Case Report).
AB  - Anaesthetic management for caesarean section in a case of peripartum
      cardiomyopathy is reported. Various anaesthetic problems in such a case are
      discussed.

PMID- 28769205
TI  - ALVEOLAR PROTEINOSIS (A Case Report).
AB  - A case of pulmonary alveolar proteinosis diagnosed by open lung biopsy is being
      reported and relevant literature is discussed.

PMID- 28769206
TI  - UNUSUAL SITES OF GASTRO-INTESTINAL TUBERCULOSIS (A Report of 2 cases).
AB  - Tuberculosis of the stomach and colon is rare, and there are no pathognomonic
      clinical, radiological or gross morphological features. Unless facilities for
      endoscopic biopsy are available surgical intervention is required to clinch the
      diagnosis and to treat the complications. One case each of gastric and colonic
      tuberculosis is reported.

PMID- 28769207
TI  - ELECTRON MICROSCOPY IN LUPUS NEPHRITIS (A Case Report).
AB  - A female patient aged 8 years presented with mild proteinuria and microscopical
      haematuria, The serological markers and histological findings in renal needle
      biopsy were inconclusive. Ultrastructural study revealed features of lupus
      nephritis. Case is presented to elucidate value of electron microscopy in such
      cases.

PMID- 28769208
TI  - RECOMMENDATION FOR HEPATITIS - B VACCINATION.

PMID- 28769209
TI  - RENAL TRANSPLANTATION IN INDIA : A FRESH LOOK.

PMID- 28769211
TI  - INTRAOCULAR TENSION VARIATIONS WITH ELECTROCONVULSIVE THERAPY.
AB  - Intraocular tension variations following modified and direct ECT were studied in
      40 psychiatric patients. A significant rise of intraocular pressure occurred
      under both conditions, but was more marked and longer lasting when
      succinylcholine was used.

PMID- 28769210
TI  - OUR EXPERIENCE IN PC IOL IMPLANTATION IN CASES OF POSTERIOR CAPSULAR BREAKS.
AB  - We implanted posterior chamber intra ocular lenses (PC IOL) in 107 eyes with
      posterior capsular breaks. Left over posterior capsular frill at the periphery
      was used to hold and support the PC IOL. After a median follow up of 2.5 years,
      96.9% of the patients who developed per operative posterior capsular break and
      67.56% who had pre-existing capsular breaks achieved 6/12 or better visual
      acuity. Remaining 32.44% of the patients with pre-existing capsular break due to
      previous surgical intervention or trauma achieved 6/18 or worse visual acuity.

PMID- 28769212
TI  - EVALUATION OF NON-CARDIAC CHEST PAIN.
AB  - A series of five cases of non-cardiac chest pain is being reported. In all cases,
      a detailed cardiac work up excluded coronary artery disease (CAD). Upper gastro
      intestinal endoscopy was found to be useful. Gastro esophageal reflux disease
      (GERD) was diagnosed in three cases. The diagnosis of esophageal disease was
      clinical in the other two. All patients responded well to further treatment and
      have been followed up for six months to two years.

PMID- 28769213
TI  - A SIMPLE COLD STAINING METHOD FOR ACID FAST BACILLI.
AB  - Sputum from 105 cases of pulmonary tuberculosis were studied. Direct and post
      concentration smears were stained by Ziehl - Neelsen (ZN) and cold staining
      methods. The cold staining method is simple, because it eliminates heatingof
      stain. For direct smear, the correlations of cold staining procedure with
      conventional ZN method was 93% and for post concentration smear it was 100%.

PMID- 28769214
TI  - CHANGING TRENDS OF LEPROSY IN ARMED FORCES.
AB  - A total of 651 cases of leprosy were hospitalised from Jan 1987 to Dec 1992. Each
      patient underwent haemogram, total and differential white cell count, urinalysis,
      liver function tests, skin slit smear for AFB and skin biopsy. Nerve conduction
      studies, electomyographic studies and nerve/nerve sheath biopsies were undertaken
      as and when indicated. These patients were managed with multidrug therapy.
      Paucibacillary (PB) leprosy accounted for 476 (73.1%) cases which comprised of
      indeterminate leprosy 90 (13.8%), tuberculoid leprosy 14 (2.2%), borderline
      tuberculoid leprosy 310 (47.6%) and neuritic leprosy 62 (9.5%). The remaining 175
      patients (26.9%) were multibacillary (MB) which included borderline leprosy 9
      (1.4%), borderline lepromatous leprosy 129 (19.8%) and lepromatous leprosy 37
      (5.7%) patients. There were total 153 patients in 1987. This number declined to
      44 in 1992. PB declined from 113 in 1987 to 39 in 1992 and MB cases from 40 to 5.

PMID- 28769215
TI  - NEW SUSPENSION DEVICE FOR LARYNGEAL ENDOSCOPIC PROCEDURES.
AB  - In view of the economic constraints in acquiring sophisticated equipments in
      service hospitals, a new suspension device for endolaryngeal surgery using
      anaesthetic laryngoscope and routinely available tonsillectomy instruments has
      been developed. This device is a modification of Ijadoula's suspension
      laryngoscope.

PMID- 28769216
TI  - PSYCHIATRIC EVALUATION OF HUMAN IMMUNODEFICIENCY VIRUS SEROPOSITIVES IN ARMED
      FORCES.
AB  - Fifty five Armed Forces personnel detected to be seropositives for human
      immunodeficiency virus were the subjects of the study. After baseline clinical
      evaluation, laboratory investigations and Centre for Disease Control
      classification, through a semistructured interview, their sexual orientation,
      behaviour and psychiatric morbidity were assessed. Sixtynine percent had another
      sexually transmitted disease as comorbidity. Heterosexual contact was responsible
      for the infection in 54 out of 55 subjects. Seven patients were freshly diagnosed
      to have psychiatric illness.

PMID- 28769217
TI  - HYPOFIBRINOGENEMIA (A Report of Two Cases).
AB  - Hypofibrinogenemia is an uncommon bleeding disorder. Two siblings with mild
      bleeding diathesis were investigated and diagnosed as suffering from this
      disorder. The cases are discussed keeping in view of their rarity.

PMID- 28769218
TI  - IMPACTED RIGHT UPPER CENTRAL INCISOR AND TRANSPOSITION OF TWO OTHER ANTERIOR
      TEETH ON THE SAME SIDE (A Case Report).
AB  - A young boy presented with an uncommon finding of impaction of upper right
      central incisor and transposition of canine and lateral incisor on the same side.
      Esthetic management of his cosmetic problem which included fixed appliance
      therapy followed by light cure restorations is discussed.

PMID- 28769219
TI  - ANEURYSMAL BONE CYST IN THE MANDIBLE (A Case Report).
AB  - Aneurysmal bone cyst is commonly seen in the long bones and vertebrae and is rare
      in the jaws. Its association with other lesions of the bone has been stressed by
      many workers. Because of its variable radiological appearance, diagnosis of the
      lesion is established by histopathological examination. A case of aneurysmal bone
      cyst occurring in the mandible is reported.

PMID- 28769220
TI  - SUBACUTE SCLEROSING PANENCEPHALITIS (A Report on Two Cases).
AB  - We report two cases of subacute sclerosing panencephalitis (SSPE) which is a
      rare, late neurological sequel, of measles infection acquired in childhood. The
      diagnosis was reached by adopting criteria defined by Dyken. Past history of
      measles was present in both the cases and they showed high titres of measles
      specific antibody in CSF and serum by quantitative ELISA.

PMID- 28769221
TI  - ELONGATED STYLOID PROCESS SYNDROME (EAGLE'S SYNDROME).
AB  - A 45 year old man presented with persistent pain in throat and otalgia. Clinical
      and radiographic evaluation confirmed the diagnosis of elongated styloid process
      syndrome. Surgical shortening of the styloid processes gave relief. The
      etiopathogenesis, presentation and management of the condition is discussed.

PMID- 28769222
TI  - INADEQUACY OF ACTIVE IMMUNIZATION ALONE IN PREVENTION OF RABIES (A Case Report).
AB  - A case of dog bite where prompt immunization with antirabies vaccine alone proved
      inadequate in prevention of fatal rabies is reported to emphasize upon the need
      of concomitant passive immunization with either human rabies immune globulin or
      equine antiserum.

PMID- 28769223
TI  - RUPTURE SINUS OF VALSALVA.

PMID- 28769224
TI  - STORAGE AND RETRIEVAL OF MYCOBACTERIUM TUBERCULOSIS ON FILTER PAPER STRIPS.

PMID- 28769225
TI  - RESURGENCE OF MT MALARIA AMONGST TROOPS IN THE NORTH EAST: Author's Reply.

PMID- 28769226
TI  - RESURGENCE OF MT MALARIA AMONGST TROOPS IN THE NORTH EAST.

PMID- 28769227
TI  - RESURGENCE OF MT MALARIA AMONGST TROOPS IN THE NORTH EAST: Author's Reply.

PMID- 28769228
TI  - RESURGENCE OF MT MALARIA AMONGST TROOPS IN THE NORTH EAST.

PMID- 28769229
TI  - QUEEN MARY'S TECHNICAL INSTITUTE.

PMID- 28769230
TI  - THROMBOLYSIS IN MYOCARDIAL INFARCTION.

PMID- 28769231
TI  - RANDOMISED, CONTROLLED, BLINDED FIELD TRIAL ON THE EFFICACY OF BIOCIDE
      FORMULATION (BACILLUS SPP.) IN THE CONTROL OF MOSQUITO VECTORS.
AB  - A randomised, controlled, blinded field trial was conducted in a large cantonment
      area, to study the efficacy of the biocide formulation (Bacillus spp.)
      indigenously produced by Central Drug Research Institute, Lucknow, India, as a
      mosquito larvicide, in comparison with Fenthion and Temephos. The study revealed
      that the biocide formulation in dosage of 5 grams per square metre brought about
      a very high level of control of culicine larvae from third day of application and
      the effect persisted till at least 28 days (median values of percentage reduction
      achieved being 93% to 100%). This effect was statistically significant from 7th
      to 28th day, as compared to Fenthion, Temephos or the biocide in dosage of 2
      grams per square metre. Fenthion, on the other hand was statistically more
      efficacious in bringing about a quick reduction, with a 100% reduction being
      obtained within a day, but the effect declined to a low level by 7th day.

PMID- 28769232
TI  - STUDY OF SERUM AND BILE FROM PATIENTS OF CHOLELITHIASIS IN NORTH-EASTERN INDIA.
AB  - Biochemical analysis of serum and bile from patients with cholelithiasis hailing
      form north-eastern India was done to provide pointers for lithogenicity. In
      comparison to controls, patients with cholelithiasis showed significant increase
      in serum phospholipid levels and lecithin cholesterol acyl transferase activity
      was significantly decreased. Enzymes like gamma glutamyl transferase, aspartate
      aminotransferase, alanine aminotransferase and alkaline phosphatase showed a
      small though significant increase as compared to controls, suggesting evidence of
      subclinical hepatic dysfunction and probable evidence of relative bile stasis.
      Levels of cholesterol, lecithin and lecithin cholesterol acyl transferase
      activity were seen to be increased in gall bladder bile as compared to hepatic
      duct bile.

PMID- 28769233
TI  - COMPARATIVE EFFICACY OF DIAGNOSTIC PROCEDURES IN PNEUMONIA IN CHILDREN.
AB  - Various investigative methods used in diagnosis, in 200 children with pneumonia,
      were analyzed to establish the diagnostic superiority. Lung juice aspirate
      culture yielded 52.4% positivity and laryngeal swab culture 52%. Gastric aspirate
      culture was positive in 36% cases and blood culture positivity was in 10% cases
      only. Thus laryngeal swab culture is as effective as lung-juice aspiration
      culture in the isolation of the organisms causing lower respiratory tract
      infections. Gastric aspirate smear examination for polymorphonuclear leucocyte
      count is helpful in screening bacterial pneumonias.

PMID- 28769234
TI  - SOLITARY RECTAL ULCER: CLINICO PATHOLOGICAL PROFILE OF A STUDY.
AB  - Eighteen rectal biopsies of eleven patients were histologically diagnosed as
      solitary rectal ulcer (SRU) during a period of three years. Their clinical and
      sigmoidoscopic features were analysed. Correct clinical diagnosis of SRU was made
      in only two out of eleven cases, the rest were diagnosed after sigmoidoscopy and
      biopsy. Presenting features were protean predominated by an altered bowel habit
      or bleeding per rectum. Sigmoidoscopically the location of the lesion varied from
      6 to 12 cm from the anal verge. Anterior rectal wall was more commonly affected
      (10 out of 11 cases). Single rectal ulcer was found in 7 patients, other 4
      showing multiple ulcers or polypoidal non-ulcerative lesions. Three patients
      required multiple biopsies. Prominent histological findings were obliteration of
      lamina propria by fibromuscular strands, splaying and hypertrophy of muscularis
      musosae as well as infiltrate in both these layers. The necessity of biopsy to
      diagnose SRU is stressed.

PMID- 28769235
TI  - EPIDEMIOLOGY OF UPPER AERODIGESTIVE CANCERS AMONG ARMED FORCES PERSONNEL AND
      THEIR FAMILIES.
AB  - Cancers of the oral cavity, pharynx, and esophagus are now suspected to have
      common etiologic factors and have been grouped together as "upper aerodigestive"
      cancers. Since this grouping is of relatively recent origin there have been no
      epidemiological studies on this group among Armed Forces personnel. 114 cases of
      upper aerodigestive cancers and an equal number of controls were studied. The
      largest number of cases were in the age group of 40-49 years with male
      preponderance. Lower level of education, smoking, quid chewing, and alcohol use
      were found to be the major risk factors for these cancers. A dose response
      relationship was observed for smoking, quid chewing and alcohol intake.

PMID- 28769237
TI  - EFFECTS OF ELECTROCONVULSIVE THERAPY ON CARDIOVASCULAR SYSTEM.
AB  - Effects of electroconvulsive therapy on the pulse rate, blood pressure and
      electrocardiogram were studied in forty consecutive physically healthy inpatients
      undergoing ECT for their psychiatric disabilities. Tachycardia and elevated blood
      pressure occurred frequently. Sinus arrhythmias, atrial and ventricular premature
      beats and minor ST-T changes were also observed. All these changes reversed
      within thirty minutes.

PMID- 28769236
TI  - PSYCHIATRIC EFFECTS OF HYSTERECTOMY.
AB  - An excess of psychiatric symptoms in post-hysterectomy women have been reported
      by some authors but denied by others. Thirty six women undergoing hysterectomy
      for non-malignant pathologies were compared with equal number of comparable
      patients who underwent other gynaecological operations. Patients were assessed
      pre- and post-operatively by semi-structured psychiatric interview, Sinha's
      anxiety scale and Hamilton's depression rating scale. Patients undergoing
      hysterectomy were significantly more anxious and depressed both pre- and post
      operatively as compared to the control patients. Hysterectomy was not associated
      with significantly higher psychiatric morbidity.

PMID- 28769238
TI  - PREVALENCE OF ENDEMIC GOITRE IN SCHOOL CHILDREN: SHIRUR (DIST. PUNE,
      MAHARASHTRA).
AB  - A survey for estimation of goitre in school children in the Rural Health Training
      Centre, Shirur area was undertaken. A total of 4664 students from 17 schools were
      surveyed. The goitre prevalence was found to be 59.8% with visible goitre rate of
      6.2% in pre- and peri-adolescent (10-19 years) age group. Thus a highly endemic
      goitre focus was located in Shirur, area in Pune District (Maharashtra). This
      area is located on the eastern tail-end slopes of Sahyadri Hills in Balaghat
      ranges, situated at an altitude of 533 metres. The area is generally drought
      prone and receives scanty rain, with poor agricultural practices. Environmental
      deficiency of iodine was found to be the main cause for this high prevalence of
      goitre.

PMID- 28769239
TI  - A MANAGEMENT INFORMATION SYSTEM FOR MEDICAL SERVICES AT COMMAND HEADQUARTERS.
AB  - Management information system (MIS) is increasingly being used for information
      storage, handling, processing and retrieval of data for improving the services
      provided by any organisation. It allows quick decision making for overall
      functional improvement. Headquarters Central Command (Medical) Lucknow has
      developed software for data capturing in respect of six important functional
      areas. These include employability and availability of specialist officers,
      assessment of hospital services through functional update and monitoring team
      (FUMTs), patient satisfaction survey, user commanders opinion, state of critical
      items of hospital clothing and modernisation of hospitals. This automation has
      resulted in quick and scientific decision making for improving the medicare
      services to the clientele.

PMID- 28769240
TI  - ROLE OF DIRECT BONDING MOLAR TUBES IN FIXED APPLIANCES BY BEGG'S TECHNIC.
AB  - Use of direct bonding molar tubes saves chair side time in orthodontic treatment.
      It eliminates the need of painful procedure of tooth separation, and discomfort
      during band adaptation is avoided. By use of direct bonding tubes, oral hygiene
      improves and danger of decalcification of enamel is avoided.

PMID- 28769241
TI  - NATIONAL TUBERCULOSIS CONTROL STRATEGY IN THE POST HIV PERIOD.
AB  - The tuberculosis situation in the country is a matter of great concern since the
      disease has not been contained. The problem has been further compounded by the
      emerging problem of HIV infection in the country together with development of
      multi-resistant tubercle bacilli. There is, therefore, a need to change our
      National Tuberculosis Control Strategy without disturbing the basic
      infrastructure of the National Tuberculosis Programme. Changes such as
      reinforcement of the District Tuberculosis Centre, HIV and drug sensitivity
      testing, giving up of long term chemotherapy, BCG vaccination policy,
      chemoprophylaxis policy and involvement of Non-Governmental Organisations and
      general practitioners are suggested.

PMID- 28769242
TI  - A MODIFIED SUCTION DRAINAGE DEVICE.
AB  - A simple modified suction drainage device made from Gibbon catheter and
      intravenous fluid glass bottle is described. It is cheaper than the suction
      drains available in the market and useful to general surgeons in peripheral
      hospitals.

PMID- 28769243
TI  - ANAESTHESIA FOR CONGENITAL LOBAR EMPHYSEMA: A Case Report.

PMID- 28769244
TI  - ACUTE ACALCULOUS CHOLECYSTITIS: A Report Of Three Cases.

PMID- 28769245
TI  - KARTAGENER'S SYNDROME - REVISITED: A Case Report.

PMID- 28769246
TI  - HALLGREN'S SYNDROME: A Case Report.

PMID- 28769247
TI  - PNEUMOCOCCAL DACRYOCYSTITIS: Three Interesting Cases.

PMID- 28769248
TI  - PATHOLOGICAL JEALOUSY TREATED WITH PIMOZIDE: A Case Report.

PMID- 28769249
TI  - FRACTURED TRACHEOSTOMY TUBES: A PER-OPERATIVE EMERGENCY.

PMID- 28769250
TI  - COLLOID CYST OF THE THIRD VENTRICLE: A Case Report.

PMID- 28769251
TI  - UNREDUCED ANTERIOR DISLOCATION OF THE HIP: A Case Report.

PMID- 28769252
TI  - PERIPARTUM CARDIOMYOPATHY AND ANAESTHESIA.

PMID- 28769253
TI  - PERIPARTUM CARDIOMYOPATHY AND ANAESTHESIA: Author's Reply.

PMID- 28769254
TI  - TUMOUR ASSOCIATED BLOOD EOSINOPHILIA.

PMID- 28769255
TI  - MEDICAL RESEARCH AT HIGH ALTITUDE.

PMID- 28769256
TI  - ENTERIC FEVER - CULTURE AND SENSITIVITY PATTERN AND TREATMENT OUTCOME.
AB  - One hundred cases of enteric fever in the age group of 6 months to 12 years were
      analysed with respect to culture sensitivity pattern and treatment outcome.
      Patients were divided into 5 treatment groups - chloramphenicol, amoxycillin,
      trimethoprim-sulfamethoxazole + furazolidine, gentamicin + cephalexin and
      ciprofloxacin. Out of 91 culture positive cases, 100% were sensitive to
      ciprofloxacin followed by gentamicin (84.9%), cephalexin (83.6%), furazolidine
      (36.6%), trimethoprim-sulfamethoxazole (34.1%), chloramphenicol (34.0%) and
      amoxycillin (23.8%). In 60 cases resistant to chloramphenicol, resistance to
      other drugs varied from 20 to 88.3%. The treatment response was 100% to
      ciprofloxacin, 72.7% to chloramphenicol, 50% to gentamicin + cephalexin, 38.5% to
      trimethoprim-sulfamethoxazole + furazolidine and 12.5% to amoxycillin. Out of 48
      cases who did not respond to initial regimen, 33 were treated successfully with
      ciprofloxacin and remaining with other drug regimens. Time taken for
      defervescence was shortest with gentamicin + cephalexin (4.6+/-2.0 days) followed
      by ciprofloxacin (6.1+/-2.5 days) and chloramphenicol (6.4+/-3.5 days). There
      were 3 deaths in this study.

PMID- 28769257
TI  - AIRWAY OBSTRUCTION IN CHILDREN.
AB  - Seventeen children presenting with airway obstruction have been studied to
      highlight the similar clinical features of different etiological conditions,
      their diagnostic limitations, and the importance of early bronchoscopy. There
      were 8 patients with foreign body in lower airway, out of which 6 were vegetable
      foreign bodies. Few rarer conditions like membranous laryngotracheobronchitis,
      subglottic hemangioma and acyanotic congenital heart disease producing airway
      obstruction have been highlighted. There were 2 deaths in the study unrelated to
      endoscopic procedure.

PMID- 28769258
TI  - ALCOHOL INDUCED ELECTROCARDIOGRAPHIC CHANGES.
AB  - Statistically significant increased incidence of electrocardiographic
      abnormalities were noted in 70 male patients with alcohol dependence compared to
      equal number of age and sex matched controls.

PMID- 28769259
TI  - STUDY ON INTEROBSERVER AGREEMENT IN A GOITRE PREVALENCE SURVEY.
AB  - Observers differ in their judgment while assessing physical signs in a patient.
      We had undertaken a goitre prevalence survey amongst school students in a Rural
      Health Training Centre, Pune district (Maharashtra) during October 1992. Four
      teams of trained observers were used for detection of goitre. This study was
      undertaken to estimate the extent and acceptability of interobserver agreement
      amongst the four teams. Observer variation/agreement was measured by two methods
      viz. kappa coefficient and proportion of agreement. The proportion of agreement
      appears to be a better measure of observer agreement as it could make a
      distinction between normality (absence of goitre) and abnormality (presence of
      goitre). In the present study, the proportion of agreement for abnormality ranged
      between 0.62 - 0.83. This measure was considered as indicating a good
      interobserver agreement in detecting goitre in the survey that was undertaken.

PMID- 28769260
TI  - EPIDURAL ANALGESIA FOR LABOUR IN ARMED FORCES HOSPITALS: A PRELIMINARY STUDY TO
      ASSESS FEASIBILITY AND ACCEPTANCE.
AB  - A pilot project to assess the feasibility of using epidural analgesia for labour
      was undertaken in an Armed Forces hospital. Effectiveness of the technique,
      acceptability by patients and nursing staff was assessed. Forty parturients were
      offered labour analgesia after explaining the procedure. A single-use 16 G Romson
      epidural catheter was placed in L2-3 or L3-4 space. Injection bupivacaine (0.25%)
      10-14 mL was used as an initial dose. An hourly dose of 0.125% bupivacaine (10-12
      mL) was given till the onset of second stage. Good to excellent analgesia during
      first stage was experienced by 34 patients. Marginal second stage prolongation
      was noticed but without any adverse neonatal effects. Analgesia was
      unsatisfactory during second stage in 25% patients. Instrumental delivery was
      required in 17% patients (LSCS - 10% and vacuum extraction - 7%). Procedure was
      accepted very well by 37 patients and they were satisfied with the pain relief.

PMID- 28769261
TI  - CONTINUOUS MONOFILAMENT POLYAMIDE (LOOP) SUTURE IN THE REPAIR OF RECURRENT AND
      COMPLICATED INCISIONAL HERNIA.
AB  - Surgery for recurrent incisional hernia is followed by further recurrence in
      nearly half the patients. Majority of these failures are due to wound
      complications and factors which give rise to an increased strain on the suture
      line. In an effort to counter the risk factors, continuous monofilament nylon
      loop suture was used in the anatomical repair of 15 patients with recurrent and
      complicated incisional hernia. After a median follow up of 14 months only one
      patient (6.6%) developed a recurrence, despite selecting only poor-risk patients.
      This technique for anatomical repair of incisional hernia seems safe and
      dependable.

PMID- 28769262
TI  - MODIFIED BROMOPHENOL BLUE DYE BINDING METHOD FOR QUANTITATION OF MICROALBUMINURIA
      IN DIABETES MELLITUS.
AB  - Albumin excretion in microalbuminuria range is one of the earliest manifestation
      of nephropathy, specially in diabetes mellitus. The modified dye binding method
      using bromo-phenol blue was studied in 27 healthy controls and 54 patients of
      diabetes mellitus, negative for albuminuria by albustix test. The analytical
      recovery (99.4 to 104.0%), within run coefficient of variation (0.8 to 0.36%) and
      day-to-day coefficient of variation (2.39 to 0.82%), for low and higher range
      were within acceptable limits. The values in controls ranged as follows: urinary
      albumin concentration (mg/L) 7.7 - 28.4 in 2-hour specimen and 10.3 - 29.2 in
      overnight specimen; albumin excretion rate (ug/min) 7.8 - 29.7 in 2-hour and 9.2 
      29.6 in overnight specimen; and albumin creatinine ratio (mg/g) 10.6 - 29.6 in 2
      hour and 11.9 - 29.6 in overnight specimens. Correlation analysis of various
      albumin excretion parameters revealed excellent correlation between estimations
      from overnight and 2-hour samples for albumin-creatinine ratio (r = 1.00) and
      albumin excretion rate (r=0.96). Equally good correlation was observed between 2
      hour albumin-creatinine ratio and albumin excretion rate (r=0.95). In 10 of 54
      patients excretion rate was more than 200 ug/min and could have been detected by
      repeat albustix test. Of the 36 positive for microalbuminuria, 21 had one or more
      target organ involvement. There was no target organ involvement in 8 patients
      negative for microalbuminuria. Screening for microalbuminuria by this simple and
      economic method, using 2-hour albumin-excretion rate or albumin-creatinine ratio
      could be one of the earliest investigations in diabetic patients.

PMID- 28769263
TI  - THYROID HORMONES IN NON-INSULIN-DEPENDENT DIABETES BEFORE AND AFTER THERAPY.
AB  - Twenty patients of non-insulin-dependent diabetes mellitus (NIDDM) (15 males and
      5 females) who developed secondary failure to oral hypoglycaemic drugs, were
      evaluated for thyroid hormone abnormalities before and after control of diabetic
      state with insulin. Blood glucose (mean +/- SEM mg/dL) fasting and post prandial
      levels were 260+/-16 and 370+/-20 respectively before therapy. After 15 days of
      intensive insulin therapy these levels fell to 110+/-14 and 130+/-12 respectively
      (p < 0.005). Glycosylated haemoglobin percent (GHb%) (mean +/- SEM) was 10+/-0.4
      before therapy and after therapy it fell to 9.2+/-0.3 (p < 0.05). Serum tri
      iodothyronine levels (mean +/- SEM ng/mL) were 0.55+/-0.03 which was
      significantly lower (p < 0.05) as compared controls. After therapy it
      significantly (p < 0.05) rose to 1.22+/-0.08). Serum thyroxine (T4) (mean +/- SEM
      mcg/dL) was 8.5+/-0.6 before therapy and it did not change significantly after
      therapy. Serum reverse tri-iodothyronine (rT3) values of (mean +/- SEM ng/dl)
      0.24+/-0.05 were higher before therapy and decreased to 0.20+/-0.82 after
      therapy. However thyrotropin (TSH) values before and after therapy remained same.
      There was no significant change in TSH response to thyrotropin releasing hormone
      (TRH) before and after control of diabetic state. It was concluded that
      peripheral changes in T3, T4 and rT3 (low T3, high rT3 and low or normal T4)
      occurred in uncontrolled diabetic state. However, pituitary thyrotroph function
      in NIDDM with ideal body weight was not significantly affected.

PMID- 28769264
TI  - TOTAL PARENTERAL NUTRITION.
AB  - Total parenteral nutrition has been used in clinical practice for over a quarter
      of a century. It has revolutionized the management of potentially fatal condition
      like the short bowel syndrome in infants as well as adults. Refinements in
      techniques have led to development of sophisticated catheters and delivery
      systems. Better understanding of human nutrition and metabolic processes has lead
      to formulation of scientific parenteral solutions to suit specific situations.
      This article addresses the role of total parenteral nutrition in modern surgical
      practice.

PMID- 28769265
TI  - AGAROSE GEL ELECTROPHORESIS AS SCREENING TEST FOR MULTIPLE MYELOMA CASES.
AB  - OBJECTIVE: To study effectiveness of agarose gel electrophoresis as a screening
      tool for early detection of multiple myeloma. DESIGN: A prospective study in OPD
      setting. PATIENTS: Two hundred and nineteen patients (126 females and 93 males)
      in the age group of 28-82 year referred to Department of Physical Medicine and
      Rehabilitation from various departments for treatment of unexplained pains and
      aches (with or without osteoporosis). They had been investigated and were
      adjudged organic disease free. INTERVENTION: Agarose gel electrophoresis was
      carried out on sera of these patients. Bone marrow aspiration was done for all
      those patients whose serum showed a monoclonal protein peak. Characterisation of
      M peak was also carried out by Immunoelectrophoresis. MAIN RESULT: Out of the 219
      patients, sera of 29 patients showed a monoclonal protein peak.
      Immunoelectrophoresis and bone marrow aspiration confirmed the diagnosis of
      multiple myeloma in these patients. 17 were male and 12 were female patients. All
      of them were over 50 years of age. CONCLUSION: Agarose gel electrophoresis was
      found to be very sensitive test for early detection of multiple myeloma cases.
      Hence it was strongly recommended to be used as a screening test for all elderly
      people who present with unexplained aches and pains with or without osteoporosis.

PMID- 28769266
TI  - CAN IMMUNOHISTOCHEMISTRY DISTINGUISH BETWEEN PRIMARY AND METASTATIC HEPATIC
      CARCINOMA?
AB  - OBJECTIVE: To determine if immunohistochemistry is useful to distinguish between
      primary and metastatic hepatic carcinoma. STUDY DESIGN: Cases of hepatocellular
      and adenocarcinoma of liver from surgical and autopsy pathology files as
      diagnosed on routine histopathology with the help of haematoxylin-eosin stain.
      PATIENTS: Thirty four patients with hepatic space - occupying lesions (a single
      lesion in 6 patients, multiple lesions in 5 patients and unspecified in remaining
      23 patients). The histopathology diagnosis included 14 hepatocellular carcinoma
      (HC), 10 cholangiocarcinoma (CC), 7 metastatic carcinoma (MC) (colonic: n=4,
      pancreatic: n=2, mammary: n=l) and three cases were unclassified. INTERVENTION:
      The paraffin embedded blocks of biopsy and autopsy cases were taken out and
      sections of 4 um thickness were cut. The immunohistochemistry staining was
      carried out by using a panel of 7 monoclonal antibodies. The monoclonal
      antibodies which were used were as follows - a fetoprotein (AFP), alpha 1
      antitrypsin (AAT), monoclonal carcinoembryonic antigen (MCEA), myelomonocytic
      antigen (Leu-Ml), tumour associated glycoprotein (B72-3), A-subunit coagulation
      Factor XIII (Factor XIIIa) and blood group substance (Lex). MAIN OUTCOME
      MEASURES: Sections were defined as immunohistochemically 'positive' if definitive
      crisp labelling was seen in atleast 10% of tumour cells by two observers. The
      positive staining was classified as either predominantly cytoplasmic or
      membranous or both. The presence or absence of nuclear staining was also noted.
      MAIN RESULTS: The typical immunoreactivity of HCs included positivity for AAT,
      AFP and factor XIIIa and no staining for B 72-3 and Leu-Ml. Of 14 patients who
      were originally diagnosed as having HC, AAT was expressed in 86% and AFP was
      expressed in cytoplasm in half of the patients. Factor XIIIa displayed
      cytoplasmic reactivity in 71% cases of HC. Lex was present focally in 3 cases of
      HC, as was monoclonal CEA. These 3 cases showed features of
      hepatocholangiocarcinoma. In all 10 cases of CC there was staining for both Leu
      Ml and Lex. The pattern of reactivity was cytoplasmic for Leu-Ml and it was both
      cytoplasmic and membranous for Lex. In 6 cases there was expression of B72-3 and
      monoclonal CEA in cytoplasm. None of the cases of CC showed staining for AFP and
      AAT only one case showed staining for AAT and factor XIIIa. As far as MC is
      concerned, there was expression of both Leu-M, and Lex in a cytoplasmic
      distribution in all the seven cases. The membranous accentuation of Lex seen in
      all cases of CC was not present in the cases of MC. Four of the 7 cases of MC
      showed reactivity for B72-3 as well and the staining pattern of Leu-M, and B72-3
      was predominantly both cytoplasmic and membranous. In 3 of the 7 cases of MC,
      there was expression of monoclonal CEA, in 1 case there was expression of AAT and
      in 2 cases there was expression of factor XIIIa. CONCLUSIONS: Histologic
      differentiation of HC from CC and MC can be greatly aided by immunohistochemical
      studies. Using a panel of 7 antibodies, cases of HC displayed cytoplasmic
      reactivity for AAT, AFP and factor XIIIa. Cases of CC showed membranous and
      cytoplasmic reactivity for Lex but only cytoplasmic reactivity for Leu-M, and B72
      3. On the other hand cases of MC showed only cytoplasmic staining but not
      membranous accentuation for Lex but Leu-M, and B72-3 showed membranous as well as
      cytoplasmic staining. The antibody MCEA showed variable results and hence was
      considered not useful. Therefore the results strongly suggest that a panel of 6
      monoclonal antibodies (except MCEA) will greatly help in differentiating between
      primary and metastatic carcinoma.

PMID- 28769267
TI  - MIRIZZI'S SYNDROME: AN UNUSUAL CAUSE OF OBSTRUCTIVE JAUNDICE: A Case Report.

PMID- 28769268
TI  - THYROID SURGERY AND A MISSED DIFFICULT AIRWAY: A Case Report.

PMID- 28769269
TI  - BENIGN SCHWANNOMA TAIL OF PANCREAS: A Case Report.

PMID- 28769270
TI  - INFANTILE HEMANGIOPERICYTOMA: A Case Report.

PMID- 28769271
TI  - RUPTURE OF GRAVID HORN OF BICORNUATE UTERUS: A Case Report.

PMID- 28769272
TI  - TUBERCULOSIS OF BRAIN: PRESENTING WITH RECURRENT STROKE AND INTRACRANIAL
      HAEMORRHAGE: A Case Report.

PMID- 28769273
TI  - SYNOVIAL TUBERCULOSIS - TWO UNUSUAL CASES: A Case Report.

PMID- 28769274
TI  - EARLY DIAGNOSIS OF INTRACEREBRAL TUBERCULOMA IN CHILDREN: A Case Report.

PMID- 28769275
TI  - PREVENTING AIDS: NEED FOR A PROPERLY EVALUATED HE 'VACCINE'.

PMID- 28769276
TI  - IMMUNOMODULATION - CLINICAL APPLICATIONS.

PMID- 28769277
TI  - STUDY OF MINIMAL INHIBITORY CONCENTRATIONS AND MULTIPLE DRUG RESISTANCE PLASMIDS
      IN SALMONELLA TYPHI.
AB  - S. typhi isolated from blood cultures were tested for minimal inhibitory
      concentrations of antimicrobial drugs using an simple easily fabricated multiple
      inoculator. Multiple drug resistant S. typhi were inhibited by high
      concentrations of ampicillin, sulphamethoxazole, trimethoprim and chloramphenicol
      (> 128 mg/L) suggestive of R factor mediated resistance. They showed presence of
      a single large plasmid with molecular weight ranging from 85 to 110 megadaltons.
      Sensitive S. typhi isolates were inhibited by lower concentrations of
      antimicrobial and did not show evidence of any plasmid. All isolates were equally
      sensitive to extremely low concentrations of ceftazidime, cefuroxime,
      ciprofloxacin, norfloxacin and gentamicin (< 0.5 mg/L).

PMID- 28769278
TI  - AEROMEDICAL ASPECTS OF CONTACT LENSES (SOFT AND SEMISOFT).
AB  - A comprehensive clinical study on the effects of various aviation stresses on
      soft and semisoft contact lenses was carried out to find out their compatibility
      in aviation environment. Twenty subjects (11 aircrew and 9 non air-crew)
      participated in the study. Twelve of them were given soft lenses of water
      contents of 38%, 50% and 78% and rest 8 were given semisoft lenses of daily wear
      and extended wear type. The environmental trial consisted of exposure to hypoxia,
      rapid decompression, acceleration, pressure breathing, vibration and high
      temperature. On successful completion of environmental trials on ground
      simulators, the inflight trials on high performance aircraft, transport aircraft,
      passenger aircraft and helicopters were conducted. The soft lenses with low,
      medium and high water contents and extended wear semisoft lenses (large diameter)
      were found compatible with all types of aircraft flying.

PMID- 28769279
TI  - LEUKAEMIC INVOLVEMENT OF CENTRAL NERVOUS SYSTEM.
AB  - Eighty two patients of leukaemia consisting of 25 cases of acute lymphocytic
      leukaemia, 38 cases of acute myeloid leukaemia, 14 cases of chronic myeloid
      leukaemia and 5 cases of chronic lymphocytic leukaemia were evaluated for central
      nervous system (CNS) involvement. Speech disorders, cranial nerve palsies,
      encephalopathy, ataxia, intracranial haemorrhage, peripheral neuropathy and
      spinal cord involvement were the main neurological findings detected in 23
      (28.1%) cases. All except one were subjected to autopsy after death. Leukaemic
      infiltrations (36.6%) and intracranial haemorrhage (26.8%) were the prominent CNS
      autopsy findings. In addition, demyelination with astrocytosis (9.7%) and gliosis
      (2.4%) were seen. In all, 45 (54.9%) of the patients showed CNS involvement at
      autopsy. Thus a large number of CNS lesions were missed clinically and detected
      only on autopsy.

PMID- 28769280
TI  - IMMUNOPHENOTYPING OF ACUTE LEUKAEMIAS : A CRITICAL ANALYSIS OF 35 CASES.
AB  - Accurate classification of acute leukaemias is essential for proper case
      management. The utility of monoclonal antibodies in the diagnosis and
      classification of acute leukaemias is well established. This diagnostic utility
      relates primarily to two points : firstly the distinction between acute myeloid
      leukaemia and acute lymphoblastic leukaemia and secondly to subtypes of acute
      lymphoblastic leukaemia. Leukaemic cells were immunophenotyped using the alkaline
      phosphatase antialkaline phosphatase techniques. The monoclonal antibodies were
      very useful in distinguishing cases of acute myeloid leukaemia from acute
      lymphoblastic leukaemia. Cases of acute lymphoblastic leukaemia with CD10
      positivity showed a better prognosis. T-cell acute lymphoblastic leukaemia was
      uncommon and was associated with unfavourable prognosis. The alkaline phosphatase
      antialkaline phosphatase technique served as a reliable and convenient method for
      immunophenotyping of leukaemias.

PMID- 28769281
TI  - RORSCHACH RESPONSE PATTERNS IN ADOLESCENT SCHIZOPHRENICS.
AB  - Analysis of Rorschach response patterns of 30 adolescent schizophrenics and an
      equal number of age and sex matched normal adolescents was undertaken. Two of the
      five Thiesen's patterns associated with schizophrenia, namely pattern C and D,
      occurred significantly more frequently in Rorschach responses of adolescent
      schizophrenics as compared to normal controls.

PMID- 28769282
TI  - CARDIOVASCULAR RISK FACTOR CLUSTERING AND CORONARY ARTERY DISEASE : A 4-YEAR
      FOLLOW UP STUDY OF 257 SERVICE PERSONNEL.
AB  - Two hundred and fifty seven service personnel with established diagnosis of (a)
      silent ischaemia (40.47%) (b) Q-infarction (25.68%) and (c) non-Q-infarction
      (33.85%) along with 50 age-matched controls were subjected to stress tests before
      and after identification and control of risk factors. Lack of exercise (63.0%),
      dietetic indiscretion (47.4%) and cigarette smoking (40.4%) were the main risk
      factors. Hypercholesterolaemia (22.1%), alcohol over-indulgence (17.1%), positive
      family history (16.3%), diabetes mellitus (9.7%) and hypertension (6.2%) were
      other contributing factors. Clustering or multiplicity of risk factors was seen
      in 61.1% cases. All patients were advised for control of risk factors along with
      necessary specific therapy wherever indicated. Initial stress test was positive
      in 83.3% of the total and on repetition, after 4 years, the positivity dropped to
      45.9% with a rate of improvement of 44.9%. Patients with silent ischaemia showed
      the maximum improvement (57.8%) following the risk factor intervention. Only 4
      cases (1.56%) showed deterioration with reinfarction during the 4-year follow up.

PMID- 28769283
TI  - THE ROLE OF RAPID SLIDE CULTURE IN THE DIAGNOSIS AND MANAGEMENT OF PULMONARY
      TUBERCULOSIS.
AB  - Rapid slide culture method using human blood medium was utilized for the primary
      culture of Mycobacterium tuberculosis and the results obtained were compared with
      results of smear examination of sputum specimens from fresh cases of pulmonary
      tuberculosis. Smear and rapid slide culture results of a total of 320 patients
      were analyzed. Slide culture was positive in 104 cases whereas smears were
      positive in 90 cases. Early culture confirmation in 7 days coupled with
      positivity better than smear examination, makes rapid slide culture a better
      method for diagnosis.

PMID- 28769284
TI  - CAESAREAN SECTION - CHANGING TRENDS DURING LAST TWO DECADES.
AB  - Changing trends of caesarean section during last twenty years have been studied.
      There seems to be a gradual increase in the incidence of caesarean section over
      the years with a simultaneous decline in the perinatal mortality rate. The
      incidence of caesarean section has slowly been increasing for post-caesarean
      pregnancy, breech presentation and foetal distress. This opens up a debate as to
      what extent this increase is justifiable. The trend needs a close observation.

PMID- 28769285
TI  - STUDIES ON HBsAG IN HIV SEROPOSITIVE CASES.
AB  - Two hundred and fifty five patients with human immunodeficiency virus (HIV)
      infection were screened for hepatitis B virus surface antigen (HBsAg) over a
      period of 3 years. These patients were followed up every 6 month. 10.2% of HIV
      seropositive cases revealed presence of HBsAg. It was also observed that almost
      half (47.6%) of these cases developed carrier state.

PMID- 28769286
TI  - NESTED CASE - CONTROL ANALYSIS OF THE RISK FACTORS FOR HIGH ALTITUDE PULMONARY
      OEDEMA.
AB  - A nested case-control study was undertaken on a cohort of soldiers inducted into
      high altitude area (11000 to 16000 feet) of Western Himalayas, with the
      objectives of studying the incidence of high altitude pulmonary oedema (HAPO) and
      its association with physical exertion and certain other predetermined risk
      factors. The study indicated that the cumulative incidence of HAPO was 1.42 per
      1000 inductions. The association with moderate/strenuous physical exertion within
      24 hours of entry into high altitude was significant (Odds ratio (OR) = 3.19; 95%
      confidence limits (CL) = 1.23 to 8.15); however, this association was not
      significant for the period 24 to 48 hours or > 48 hours. Physical exertion during
      first 24 hours was also significantly associated with severity of disease (OR =
      14.67, 95% CL = 3.61 to 64.04), but not after 24 hours. Previous history of "high
      altitude sickness" was also significantly associated with HAPO (OR = 2.74, 95% CL
      = 1.12 to 6.77). Physical exertion during first 24 hours was found to carry an
      attributable risk of 2.56 per 1000 inductions and an etiologic fraction of 17.8%.
      No significant association of HAPO was observed with age, type of inductee
      (fresh/reinductee), native place, alcohol consumption and smoking.

PMID- 28769287
TI  - MYOCARDIAL REVASCULARIZATION.
AB  - Atherosclerotic coronary artery disease causes more morbidity, mortality and loss
      of economic capacity than any other group of diseases. The modalities of
      revascularization of the myocardium have undergone rapid advances with emphasis
      shifting alternately from medical methods to surgical. Lately interventional
      cardiology armed with laser technology stands at par with coronary artery bypass
      grafts.

PMID- 28769288
TI  - SCREENING PROCEDURES IN PEDIATRICS.
AB  - Pediatric health screening procedures, both prenatal and postnatal, have a
      tremendous potential in improving the health status of children and in turn
      reducing the resource burden on the parents and the State. The existing
      recommendations, inherent problems and different screening procedures are
      discussed. The need for suitable mass screening pediatric procedures in the
      Indian context is stressed.

PMID- 28769289
TI  - HYPERLIPIDEMIA IN A CHILD: A Case Report.

PMID- 28769290
TI  - MECONIUM PERITONITIS PRESENTING AS A PSEUDOCYST: A Case Report.

PMID- 28769291
TI  - FIBRODYSPLASIA OSSIFICANS PROGRESSIVA: A Case Report.

PMID- 28769292
TI  - RENAL ANGIOMYOLIPOMA CAUSING FATAL RETROPERITONEAL HEMORRHAGE: A Case Report.

PMID- 28769293
TI  - FIBROID UTERUS AN UNUSUAL PRESENTATION: A Case Report.

PMID- 28769295
TI  - OPPORTUNISTIC INFECTIONS IN AIDS (AUTOPSY OF TWO CASES).

PMID- 28769294
TI  - DAPSONE SYNDROME: A Case Report.

PMID- 28769296
TI  - HOMONYMOUS HEMIANOPIA WITH CHRONIC SUBDURAL HAEMATOMA: A Case Report.

PMID- 28769297
TI  - ANAESTHESIA FOR CONGENITAL LOBAR EMPHYSEMA.

PMID- 28769298
TI  - ANAESTHESIA FOR CONGENITAL LOBAR EMPHYSEMA: Author's Reply.

PMID- 28769299
TI  - A MODIFIED SUCTION DRAINAGE DEVICE: Author's Reply.

PMID- 28769300
TI  - A MODIFIED SUCTION DRAINAGE DEVICE.

PMID- 28769301
TI  - HIV AND TUBERULOSIS.

PMID- 28769302
TI  - LONG TERM VENOUS ACCESS IN PATIENTS WITH ACUTE LEUKEMIA AND HIGH GRADE LYMPHOMAS
      (Based on AFMRC Project 1868/91).
AB  - Twenty Hickman catheters were passed in 19 patients undergoing chemotherapy for
      acute leukemia (15 patients) and high grade lymphoma (4 patients). The catheters
      were inserted into the superior vena cava through the cephalic or external
      jugular vein with subcutaneous tunneling and exit through the anterior chest
      wall, and were functionally effective in 19 cases. The catheters remained in situ
      for a mean period of 50.5 days (range 1-266 days). The catheters were well
      tolerated eliminating the need for repeated venepuncture. The complications
      encountered were: hemorrhage - 1 case, thrombosis - 1 case, catheter related
      bacteremia - 2 cases, tunnel infection - 1 case, and exit site infection - 5
      cases. Most of the complications were managed conservatively. These catheters
      ensured safe and reliable venous access in these high risk patients during
      episodes of severe neutropenia, sepsis and thrombocytopenia.

PMID- 28769303
TI  - A CASE-CONTROL STUDY OF CARCINOMA BREAST AMONG WOMEN : AN EPIDEMIOLOGICAL RISK
      FACTOR STUDY.
AB  - A hospital based case-control study of breast cancer was carried out during
      January to November 1991 at Command Hospital Southern Command, Pune. Ninety six
      cases of female breast cancer and an equal number of matched controls were
      studied. It was found that age at menopause and age at first birth had no
      significant (p > 0.05) association with the risk of breast cancer. A significant
      association was found between attainment of menarche before the age of 12 years
      and development of breast cancer (p < 0.01). A positive history of breast cancer
      in first degree relatives was also associated with an increased risk of breast
      cancer (p < 0.05). Body anthropometry was measured in terms of absolute body
      weight (in kg) and waist to hip ratio showed a positive association. Body weight
      of more than 55 kg (p < 0.01) and WHR more than 0.86 (p < 0.01) showed a
      significant risk.

PMID- 28769304
TI  - APPLICATION OF STRATIFIED ANALYSIS IN EPIDEMIC INVESTIGATIONS : ANALYSIS OF AN
      OUTBREAK OF FOOD POISONING.
AB  - The present study demonstrates the use of stratified analysis when high (or low)
      risk is observed for two or more food items during the investigation of food
      poisoning, rather than simply implicating the item showing the highest risk. In
      this study an outbreak of food poisoning, which exhibited a clinico
      epidemiological profile of Clostridium perfringens as the possible agent, was
      investigated using a case-control typology. Evaluation of food histories showed a
      high and significant odds ratio (OR) for a mutton dish (OR = 6.45, p < 0.001) and
      peas dish (OR = 5.6, p < 0.001), while a legume dish showed a protective effect
      (OR = 0.13, p < 0.001) which proved erroneous. Stratified analysis using Mantel
      Haenszel procedure indicated that the risk due to mutton persisted even after
      adjusting for consumption of peas (adjusted OR = 4.22) or legume dish (adjusted
      OR = 4.25). The use of stratified analysis in investigating epidemics has been
      recommended.

PMID- 28769305
TI  - ECLAMPSIA : AN EXPERIENCE OF A CIVIL HOSPITAL.
AB  - Fifty two cases of eclampsia managed during 4 years at a civil hospital in Pune
      have been analyzed. The perinatal mortality was 27.20% and maternal mortality was
      1.92%. Results of magnesium sulphate therapy were found to be better than lytic
      cocktail therapy.

PMID- 28769306
TI  - MICROSOMAL AND THYROGLOBULIN ANTIBODIES IN THYROID DISORDERS.
AB  - Eighty patients with various thyroid disorders and 20 controls were investigated
      to determine antibodies against thyroglobulin and microsomal antigens by
      haemagglutination and immunofluorescent techniques. They were also tested for
      immunoglobulin profile by radial immunodiffusion methods. Patients with
      Hashimoto's disease, idiopathic hypothyroidism, and Grave's disease showed
      significant elevations of IgG. None of the patients with toxic nodular goitre or
      thyroid adenoma showed any thyroid antibodies while 69.2% patients with Grave's
      disease, 16% with euthyroid goitre, 58.3% with hypothyroidism and all the
      patients with Hashimoto's disease had microsomal antibodies by immunofluorescent
      test. Similarly, all the cases of Hashimoto's disease, 41.6% of those with
      hypothyroidism, 30% of Grave's disease patients and none of the patients with
      toxic nodule or thyroid adenoma had thyroglobulin antibodies by haemaglutination
      test. Evaluation for auto-antibodies may aid the clinician in the overall
      assessment of various thyroid disorders.

PMID- 28769307
TI  - CT-GUIDED FNAC AND BIOPSY : OUR EXPERIENCE.
AB  - Twenty five patients with mass lesions in the chest, abdomen, pelvis, and
      paraspinal region underwent contrast enhanced computed tomographic scan (CT Scan)
      followed by CT guided FNAC or Tru-cut biopsy. CT was found to be extremely
      valuable in ensuring needle placement within the lesion. It also helped in
      avoiding the necrotic areas and obtaining tissue from an area most likely to
      yield an adequate sample. A post-procedure scan helped in ruling out post
      procedure complications.

PMID- 28769308
TI  - ROLE OF RADIOLOGY IN THE DIAGNOSIS AND MANAGEMENT OF HYDATID DISEASE OF THE
      LIVER.
AB  - Twelve patients with hepatic hydatid cysts were studied for radiological
      features. All had undergone plain radiography abdomen (AP view) and ultrasound
      study. Six patients had undergone computerised tomography (CT). On plain
      radiography, curvilinear calcification was the only important positive finding (3
      cases). Ultrasonographic findings were - single thick walled cyst (2 cases),
      multiple cysts (3 cases), multilocular cysts (3 cases), internal septum/floating
      membrane (2 cases), hydatid sand (1 case), and ill-defined cyst (1 case). CT
      findings of 6 patients were : single cyst (2 cases), multiple cyst (1 case),
      multilocular cysts (1 case), and ill-defined cysts (2 cases).

PMID- 28769309
TI  - HIV IN TUBERCULOSIS.
AB  - This study was undertaken to evaluate clinical and laboratory parameters of 29
      HIV-infected male patients with tuberculosis. Out of the 243 human immune
      deficiency virus (HIV) seropositive patients, 15 (6.2%) were diagnosed to be
      suffering from tuberculosis whereas out of 3502 cases of tuberculosis random HIV
      surveillance in 350 cases showed HIV infection in 14 (4%). Mantoux positivity at
      the time of diagnosis of tuberculosis was noted in 16 (55.1%) patients, and out
      of them 17.1% showed tuberculin conversion within 2 years of detection of HIV
      infection. Diagnosis of tuberculosis was based on demonstration of acid fast
      bacilli in sputum of 8 (27.6%), and in lymphnode aspirate in 4 (13.8%).
      Tubercular granuloma was demonstrated in 3 more patients, 2 in lymphnodes and one
      in liver parenchyma. In another 14 cases, there was classical clinical
      presentation and chest radiogram findings with excellent therapeutic response.
      Chest radiograms showed pulmonary infiltrate in 20, pleural effusion in 5,
      pleural thickening in 2, and intrathoracic adenopathy in 6 patients. Exclusive
      extrapulmonary tuberculosis was present in 4 patients.

PMID- 28769310
TI  - SENSITIZATION STATE OF POTENTIAL LIVE RELATED DONOR RENAL TRANSPLANT PATIENTS.
AB  - Sensitization state of 119 patients of end-stage renal disease registered for
      live related donor transplant was assessed by determining the panel reactive
      antibody (PRA) status and the donor-specific crossmatch positivity. Eighty one
      patients (69.1%) showed no PRA, whereas 27 (22.6%) had PRA less than 10% and the
      remaining 11 patients (9.2%) displayed PRA more than 10%. The lower level of
      sensitization was related to the short dialysis period, less number of blood
      transfusions, fewer female patiente, and lesser number of retransplants. Cross
      match positive patients were in the higher PRA group (range 32-68%) as compared
      to 0-24% PRA in cross-match negative group.

PMID- 28769311
TI  - MYCOTIC KERATITIS.
AB  - Mycotic keratitis is a distressing infection and may lead to permanent blindness.
      Fifty two cases of suspected mycotic keratitis were studied from Jan 91 to Sep
      94. Specimens were collected on swabs in 20 cases and by corneal scraping in 32
      cases. Wet mount examination of the specimens revealed fungal elements in 8
      (15.4%) cases, of which 3 specimens were collected on swabs and 5 by corneal
      scraping. Fungi were isolated from a total of 12 (23.1%) specimens 5 of which
      were obtained by swabs while 7 by corneal scraping. Important pathogens were
      Fusarium spp, Aspergillus spp, Candida albicans and Cephalosporium spp. Direct
      examination of the specimens was found to be less sensitive than culture for the
      diagnosis of mycotic keratitis.

PMID- 28769312
TI  - AN EPIDEMIOLOGICAL STUDY OF SNAKE BITES IN AN AREA IN THE FOOTHILLS OF THE NORTH
      WESTERN HIMALAYAS.
AB  - Cases of snake bite amongst troops, families, and defence civilians admitted to a
      service hospital were consistently high from 1985-1988 (rate 1.24-1.56 per 1000).
      Study of the cases revealed simple measures could have prevented a large number
      of casualties which in fact became true in 1989 (rate 0.43 per 1000) when strict
      enforcement of preventive measures was practised.

PMID- 28769313
TI  - EMERGENCY TREATMENT OF OBSTRUCTING LARGE BOWEL CANCER.
AB  - Thirty cases of obstructing large bowel cancer were treated by emergency
      procedures like proximal colostomy (55%), caecostomy (3%), appendicostomy (2%),
      ileotransverse colostomy (6%), right hemicolectomy (14%), anterior resection
      (14%), Hartmann's procedure (3%) and Lahey's procedure (3%). Primary resection
      for tumours of the right colon and staged procedures for tumours of the left
      colon and rectum and are safe procedures in the management of obstructing large
      bowel cancer.

PMID- 28769314
TI  - CONTROVERSIES IN THE SURGICAL MANAGEMENT OF HYDATID DISEASE OF THE LIVER.

PMID- 28769315
TI  - TRANSJUGULAR INTRAHEPATIC PORTASYSTEMIC STENT SHUNT.

PMID- 28769316
TI  - USE OF LARYNGEAL MASK AIRWAY IN THYROID SURGERY: A Case Report.

PMID- 28769317
TI  - RECURRENT INTRACRANIAL HAEMORRHAGE DUE TO CRYPTIC ARTERIOVENOUS MALFORMATION: A
      Case Report.

PMID- 28769318
TI  - PASTEURELLA MULTOCIDA INFECTION IN A DOG BITE WOUND: A Case Report.

PMID- 28769319
TI  - FRONTOETHMOIDAL MUCOCELE: A Case Report.

PMID- 28769320
TI  - TREACHER-COLLINS SYNDROME: A Case Report.

PMID- 28769321
TI  - ACUTE ACALCULOUS CHOLECYSTITIS.

PMID- 28769322
TI  - ACUTE ACALCULOUS CHOLECYSTITIS: Author's reply.

PMID- 28769323
TI  - RENAL TRANSPLANT - AN EARLY EXPERIENCE.

PMID- 28769324
TI  - PREVALENCE AND DISTRIBUTION OF CERTAIN CORONARY RISK FACTORS IN AIR FORCE
      PERSONNEL.

PMID- 28769325
TI  - HERPES ZOSTER IN HUMAN IMMUNODEFICIENCY VIRUS INFECTION.

PMID- 28769326
TI  - CLINICAL APPLICATION OF FLOW CYTOMETRY IN LIVE RELATED DONOR RENAL
      TRANSPLANTATION.
AB  - To monitor the activity of the humoral component in graft dysfunction following
      renal transplantation using live related donors, flowcytometric cross-match
      procedure was adopted. Antidonor antibodies were detected in the sera of both pre
      and post-transplant patients using conventional serological cytotoxicity cross
      match and flowcytometric cross-match assays. In the 52 pretransplant samples no
      significant differences were observed in flowcytometric and cytotoxicity tests
      except in 2 secondary transplant cases which were negative by cytotoxicity test.
      However, in post-transplant samples, floweytometry was found to be a more
      objective and useful test than cytotoxicity testing in distinguishing 6 out of 7
      mild acute-graft-rejection episodes. Both tests were found to be negative in alt
      5 cases of cyclosporin-A nephrotoxicity, 7 cases of acute tubular necrosis and 10
      out of 11 cases of chronic rejection.

PMID- 28769327
TI  - EXPERIENCE WITH THE LARYNGEAL MASK AIRWAY IN ANAESTHESIA.
AB  - Laryngeal mask airway was used in 100 adult patients of either sex (ASA I/II)
      undergoing various surgical procedures. The duration of surgery varied from 17 to
      145 minutes. The course of anaesthesia was smooth and uneventful in all cases.
      The failure rate of insertion of LMA was 7%. The overall incidence of
      complications was 12%. LMA insertion was associated with statistically
      insignificant change in haemodynamic parameters.

PMID- 28769329
TI  - ROLE OF HYSTEROSCOPY IN DIAGNOSIS OF MENSTRUAL DISORDERS.
AB  - Hysteroscopic evaluation was carried out in 120 cases of menstrual disorders with
      no clinical positive findings. The ages of patients ranged from 20 years to 48
      years. Abnormal findings on hysteroscopy were noted in 48.3 percent (58 cases)
      and histologically abnormal lesions were observed in 35.8 percent (43 cases).
      Histological correlation with hysteroscopy was 74.1 percent Lesions like
      submucous fibroid, polyps, and uterine synechiae were diagnosed with 100 percent
      accuracy. This study suggests that hysteroscopic evaluation increases the
      diagnostic precision in patients with intra-uterine lesions and should be done in
      cases of menstrual disorders alongwith other traditional methods of evaluation.

PMID- 28769328
TI  - EMOTIONAL FACTORS IN PSORIASIS.
AB  - Levels of anxiety and depression in twenty five patients with psoriasis were
      compared with anxiety and depression levels in equal number of age and sex
      matched normal controls, patients with nonpsychosomatic medical illnesses, and
      patients with neuroses. Sinha's anxiety scale and Hamilton's depression rating
      scale were used to measure anxiety and depression respectively. Analysis revealed
      that patients with psoriasis were significantly more anxious and depressed as
      compared to normal subjects and hospitalized patients with medical illnesses.
      Psoriatics were significantly less anxious and depressed than neurotics. Five
      patients with psoriasis were dependent on alcohol. Therapeutic implications of
      these findings are discussed.

PMID- 28769331
TI  - MILITANCY TRAUMA : MAXILLOFACIAL INJURY, ANAESTHESIA AND CRITICAL CARE.
AB  - Eighty four out of 2151 militancy trauma patients sustained severe maxillofacial
      injury from Jan 1990 to March 1993. The resuscitation, stabilisation and
      intensive care of these patients was based on management priorities of primary
      resuscitation, care of airway, management of haemodynamics, oxygenation and
      monitoring. Anaesthesia was administered in a situation when the airway was
      likely to be compromised and the patients were critically sick. Initial
      ventilation and oxygenation was the most difficult and could be achieved with
      satisfactory seal around the face mask by applying water-soaked guaze pieces
      around the mouth and nose to "fill-in" the defects. Tracheal intubation could be
      accomplished with intravenous sedation by an experienced anaesthesiologist.
      Dental occlusion and wiring necessiated the placement of nasotracheal tube for 48
      72 hours after surgery.

PMID- 28769330
TI  - CLINICO-PATHOLOGICAL CORRELATION IN NEONATAL AUTOPSIES.
AB  - Of the 253 neonates admitted to a neonate intensive care unit during the period
      Jan 91 to Sep 93, 43 neonates died. Autopsy was done in 23 of these (53%). The
      mean duration of stay of the neonates in the intensive care unit prior to death
      was 5.6 days (range 2 hours to 10 days). Antemortem diagnoses included asphyxia
      neonatorum (4), meconium aspiration syndrome (2), septicemia (5), prematurity
      (3), birth trauma (2), congenital anomalies (2), hypoxic ischemic encephalopathy
      (1), and non-specific diagnosis (4). There were 6 major autopsy findings that, if
      known prior to death, would have altered clinical management and might have
      resulted in cure or prolonged survival. There were 8 additional major findings
      that, if known prior to death, would not have altered management There were 14
      minor findings related to major diagnoses but unrelated to the primary cause of
      death.

PMID- 28769332
TI  - HORMONAL MARKERS IN THE STUDY OF PITUITARY ADENOMAS.
AB  - Twenty pituitary adenomas were studied using light microscopy,
      immunohistochemistry and electron microscopy. Based on clinical manifestations of
      hormonal hypersecretion they were divided into two groups, i.e. group-I (12
      patients) with no endocrine dysfunction and group-II (8 patients) with endocrine
      dysfunction. Group-I could be further sub-divided into two groups based on IHC :
      group LA in which no hormone could be localised in the tissue (null cell
      adenomas) and group IB where hormones could be localised in the tissue (1).
      Tumours in group II, with light microscopy, were acidophil (n=5), basophil (n=1)
      or mixed (n=2) adenomas. Eight of these 20 cases were plurihormonal. Growth
      hormone, and prolactin were the commonest combination. This study has helped in
      the reclassification of the pituitary adenomas according to the hormone they
      produce.

PMID- 28769333
TI  - FIBRIN AND FIBRINOGEN DEGRADATION PRODUCTS IN MALIGNANCY.
AB  - Sixty four patients of cancer, comprising of 39 leukaemia, 8 lymphomas and 17
      cases of solid tumours were included in this study. Quantitative estimation of
      FDP, fibrinogen and platelets were done in all. Elevated levels of FDP (>= 10
      ugm/mL) were found in 29 patients. These patients were further categorised as
      decompensated, overcompensated and compensated intravascular coagulation and
      fibrinolytic syndrome on the basis of platelet counts and fibrinogen levels.

PMID- 28769334
TI  - POST-TRAUMATIC STRESS DISORDER IN POLY-TRAUMA CASES.
AB  - Six hundred and one patients, who sustained injuries in militant activities,
      admitted during a 7 month period to a zonal referral hospital were studied. The
      majority, 54.6% from the Armed Forces and 38.8% from the para-military forces,
      were in the age group of 22-53 years. There were 40 (6.7%) civilian casualties.
      These were in the age group of 20-45 years. A large number (75.7%) of the
      casualties manifested with post-traumatic stress symptoms. 24.3% of them were
      rated as post-traumatic stress disorder. Six months follow-up revealed
      persistence of post-traumatic stress disorder in 17.1% of the cases. By one year,
      42.1% who responded to the follow-up letters had persistence of post-traumatic
      stress disorder in 4.95%. Early recognition of this psychic trauma and preventive
      strategies are discussed.

PMID- 28769335
TI  - SYSTOLIC MURMURS IN APPARENTLY HEALTHY INDIVIDUALS.
AB  - Presence of a systolic murmur is not always indicative of organic heart disease
      or abnormality, especially so in asymptomatic individuals. We studied 210 young
      adults (192 males, 18 females) of the age group 16 to 23 years with systolic
      murmurs to evaluate the utility of noninvasive tests in ascertaining the presence
      or absence of heart disease. Each case was categorized after clinical evaluation
      and again after noninvasive investigations (chest radiogram, 12 lead ECG, and
      echocardiography) into 3 groups. Based on clinical evaluation alone, 190 (90.5%)
      cases had no evidence of heart disease (group A), 16 (7.6%) cases had definite
      heart disease (group C) and in 4 (1.9%) cases the presence of heart disease could
      not be ruled out definitely (group B). The recategorization after investigations
      did not alter the initial diagnosis in any of the subjects from groups A and C
      (98.1%). Two cases from group B (0.95%) changed groups whereas in the remaining 2
      cases (0.95%) from group B no definite conclusions could be reached even after
      echocardiography.

PMID- 28769336
TI  - AZATHIOPRINE INDUCED BONE MARROW SUPPRESSION IN LIVE RELATED RENAL ALLOGRAFT
      RECIPIENTS.
AB  - Over a follow-up period of 6 years, 4 out of 31 live related renal allograft
      recipients (12.9%) developed azathioprine induced bone marrow suppression.
      Presentation in 3 patients was with fever and 2 patients also had associated
      graft dysfunction. All patients had leucopenia, 2 patients in addition had
      anaemia and one patient had pancytopenia. Bone marrow suppression developed 9.6
      months (3.5-16.0 months) following transplantation and recovery followed over a
      period of 30 (18-49 days) days after withdrawal of the drug. One patient
      succumbed during the phase of bicytopenia.

PMID- 28769337
TI  - A REVIEW OF CASUALTY PENSIONARY AWARDS : ENTITLEMENT AND ASSESSMENT.
AB  - Armed Forces personnel and their families are entitled to causalty pensionary
      awards in the form of disability pension, special or family pension when
      disability or death has been due to service factors. In this article an effort
      has been made to make the medical officers in general and medical boards in
      particular aware of the existing entitlement rules, assessment guidelines,
      channel of processing and various authorities empowered to decide these claims.
      Some of the areas needing special consideration by medical boards have been
      highlighted.

PMID- 28769338
TI  - IS CLEAN DISSECTION OF CALOT'S TRIANGLE NECESSARY IN CHOLECYSTECTOMIES?
AB  - In this study when patients were followed up for post-operative symptoms, it was
      seen that the incidence of narrowing of lumen of the common bile duct was more in
      cases where the operation was done by retrograde cholecystectomy with clean
      dissection of Calot's triangle. Though this was a coincidental finding, it raises
      a doubt whether the narrowing is a result of impairment of blood supply to the
      common bile duct, which may result from clean dissection and display of Calot's
      triangle area. The above dissection removes the fascial layer over the common
      bile duct and is likely to result in damage to end-arteries piercing through it
      to the common bile duct. This conjecture requires further study in a larger
      series.

PMID- 28769339
TI  - DERMATOMAL AND DISSEMINATED VARICELLA ZOSTER LESIONS IN A HIV INFECTED
      INDIVIDUAL: A Case Report.

PMID- 28769340
TI  - INTERMITTENT ACUTE PORPHYRIA: A Report of Three Cases.

PMID- 28769341
TI  - ASSOCIATION OF VARICOSE VEINS OF LOWER EXTREMITIES WITH VARICOCELE AND
      HAEMORRHOIDS: A Case Report.

PMID- 28769342
TI  - HOLIDAY HEART SYNDROME: A Case Report.

PMID- 28769343
TI  - RESURGENCE OF MT MALARIA IN THE NORTH EAST.

PMID- 28769345
TI  - RESURGENCE OF MT MALARIA IN THE NORTH EAST: Author's Reply.

PMID- 28769344
TI  - DEFORMITIES OF HIP IN POLIOMYELITIS-CLINICAL ASSESSMENT.

PMID- 28769346
TI  - HAZARD ANALYSIS CRITICAL CONTROL POINT (HACCP) SYSTEM : A PUBLIC HEALTH NEED FOR
      THE ARMED FORCES.

PMID- 28769347
TI  - THE ILEAL NEOBLADDER - AN IDEAL BLADDER SUBSTITUTE?
AB  - The ileal neobladder was evaluated on 5 patients following radical
      cystoprostatectomy. All the patients made good post-operative recovery. Complete
      day and night continence was achieved in all by the third month. Bladder
      capacities ranged between 475 mL and 690 mL and the residual volumes between 23
      mL and 65 mL at 3 months. The neobladder pressures were below 35 mm of water.
      Ultrasound scanning and intravenous urography showed no signs of obstruction or
      reflux in the upper tracts.

PMID- 28769348
TI  - PREVENTION OF POST-OPERATIVE WOUND INFECTION IN ABDOMINAL OPERATIONS.
AB  - One hundred patients undergoing abdominal surgery were included in this
      prospective study. The role of local application of Betadine, use of synthetic
      sutures, and use of low pressure subcutaneous suction drainage were evaluated in
      preventing post-operative wound infection. The infection rate was 15 per cent
      with Betadine, 15.4 per cent with prolene, 20 per cent with subcutaneous suction
      drainage and 30.8 per cent in the control group.

PMID- 28769349
TI  - AN EXPERIENCE IN MANAGEMENT OF SURGICAL OBSTRUCTIVE JAUNDICE.
AB  - One hundred and five patients of surgical obstructive jaundice were admitted to
      Army Hospital, Delhi from July 1991 to June 1994. Patients were investigated as
      per the diagnostic protocol. The causes of obstruction were choledocholithiasis
      (24 patients), periampullary carcinoma and carcinoma head of pancreas (32
      patients), carcinoma gall bladder and cholangiocarcinoma (11 patients each). The
      procedures performed to relieve obstructive jaundice in 89 cases included
      choledochojejunostomy (17), pancreato-duodenectomy (15), hepaticojejunostomy
      (15), choledocholithotomy (12) and choledochoduodenostomy (12). Mortality was 7
      per cent in pancreatoduodenectomy and 8 per cent in palliative procedures.

PMID- 28769350
TI  - CHOLECYSTECTOMY : FUNDUS TO PORTA APPROACH.
AB  - Cholecystectomy is a commonly performed operation but there is still controversy
      whether dissection of the gall bladder should proceed from the fundus to the
      cystic duct or in the opposite direction. In usual practice the fundus-first
      method is adopted whenever difficulty is encountered in visualizing the anatomy
      of the cystic duct and Calot's triangle. Although haemorrhage is a little greater
      than with the duct-first method the risk of damage to the common bile duct or
      right hepatic artery is minimized. This article describes a brief experience with
      thirty randomized patients in whom cholecystectomies were performed with planned
      fundus-first approach.

PMID- 28769351
TI  - SUPRACLAVICULAR FIRST RIB RESECTION FOR TREATMENT OF THORACIC OUTLET SYNDROME.
AB  - Twelve patients with thoracic syndrome were operated during a 15 month period.
      Eleven patients had features of neurogenic thoracic outlet syndrome, while one
      presented with arterial ischemia due to distal embolism. The diagnosis was based
      on the characteristic history and positive stress tests. Cervical rib was present
      in 7 patients. Abnormal nerve conduction studies were present in 7 out of 8
      cases. Supraclavicular first rib resection was done in all patients in view of
      the severity of symptoms. If present, the cervical rib was also excised. There
      was no major operative complication. Eleven out of twelve patients reported
      relief of symptoms. Thoracic outlet syndrome is not an uncommon disorder and
      often goes undiagnosed. Resection of first rib via the supraclavicular approach
      gives good results in majority of the patients who have incapacitating symptoms.

PMID- 28769352
TI  - DRUG RESISTANT TUBERCULOSIS - THE EMERGING SCENARIO.
AB  - During the period April 1992 to September 1994 a total of 2288 patients of
      pulmonary tuberculosis were treated at our centre. M. tuberculosis could be
      isolated from the sputa of 1037 patients (45.3%). All the isolates were subjected
      to indirect susceptibility testing using drug incorporated Lowenstein-Jensen
      medium slants. A total of 142 (13.7%) patients showed drug resistance. Single
      drug resistance was observed in 86 (8.3%) patients whereas resistance to two or
      more drugs was observed in 56 (5.4%) patients. Patients showing initial drug
      resistance were more in number (83 cases) than those showing acquired drug
      resistance (59 cases). Resistance to streptomycin was commonest (8.3% of
      isolates) followed by isoniazid (5.7%) and rifampicin (5.0%). Multiple drug
      resistance was mostly acquired (71.4% of drug-resistant isolates).

PMID- 28769353
TI  - HEALTH AWARENESS VERSUS ECONOMIC AFFLUENCE AS DETERMINANTS OF HEALTH STATUS : A
      COMMUNITY BASED EPIDEMIOLOGICAL ANALYSIS.
AB  - A community-based cross-sectional analytic epidemiological study was undertaken
      to compare the health status of school children from two villages and to see the
      association of the school children's health status with the level of health
      awareness among parents and teachers. The two villages had only one major
      difference, i.e., one had an agriculture-based economy and was more affluent than
      the other village. The study, however, revealed that the overall morbidity and
      nutritional deficiencies were significantly less (p < 0.01) and immunization
      status significantly better (p < 0.01) among school children of the less affluent
      village, possibly because level of health awareness was significantly higher
      among parents and teachers of this village as compared to the more affluent one
      (p < 0.01). The importance of health education has been reinforced by this study.

PMID- 28769354
TI  - AN EPIDEMIOLOGICAL STUDY OF BLOOD PRESSURE AMONG SCHOOL CHILDREN.
AB  - Blood pressure was measured in 1170 school children between 5 and 15 years of
      age. Mean blood pressure was significantly higher in boys than girls in all age
      groups and a steady increase in blood pressure with age was seen in both the
      sexes. Mean blood pressure was significantly higher among children with positive
      family history of cardiovascular morbidity. Children from higher socio-economic
      strata and overweight children also showed higher blood pressure. Nine (0.77%)
      children had persistent hypertension. However, the degree of hypertension was
      mild and all these children were asymptomatic. Baseline investigations failed to
      detect any underlying pathology or target organ involvement. This study suggests
      that childhood could be a reasonably profitable time to look for such factors and
      to selectively screen children belonging to the high risk group for hypertension.

PMID- 28769355
TI  - APPLICATION OF HAZARD ANALYSIS CRITICAL CONTROL POINT SYSTEM : ANALYSIS OF A FOOD
      POISONING OUTBREAK.
AB  - The World Health Organization as well as several experts have recently
      recommended the use of hazard analysis critical control point system for
      prevention of food-borne illnesses. The present study proceeded to identify the
      hazardous operations and their critical control points by investigating, through
      a case-control design, an outbreak of food poisoning. The predominant presenting
      symptoms were watery diarrhoea and abdominal cramps. The cumulative incidence
      during this episode was 28.6 per cent, with a median incubation of 13 hours.
      Evaluation of food histories indicated a very high and significant odds ratio for
      mutton dish (OR = 6.45; p < 0.001), which persisted even after adjusting for the
      consumption of other food items through stratified analysis using the Mantel
      Haenszel procedure. Environmental assessment revealed a strong possibility of
      contamination of raw mutton at the source with animal excreta and prolonged
      storage at room temperature of cooked mutton dish. Based on these findings,
      hazardous operations were identified and critical control points and monitoring
      criteria for prevention of food poisoning have been suggested.

PMID- 28769356
TI  - SCANNING ELECTRON MICROSCOPIC STUDY OF HeLa CELL INVASION BY SALMONELLA TYPHI.
AB  - Invasion of cultured non-pliagoeytic cells by salmonella is illustrated by a
      scanning electron microscopie study of HeLa cell invasion by S. typhi. This study
      shows that after bacterial adherence the HeLa cell cytoplasmic membrane shows
      ruffling and formation of filopodia which gradually engulf the bacterium and draw
      it into the cytoplasm. The available literature is reviewed and the probable
      mechanism underlying phagocytosis is hypothesized.

PMID- 28769357
TI  - SILENT MYOCARDIAL ISCHEMIA IN HEMODIALYSIS PATIENTS - FACTOR FICTION?
AB  - Thirty eight patients underwent Holter ECG monitoring for a 48 hour period
      covering dialysis and intermediate period to detect incidence of myocardial
      ischemia manifesting as ST segment changes. Seventeen patients (44.7%) had 165
      episodes of dynamic ST segment changes lasting from 1 to 177 minutes, with
      maximum ST depression of 4 mm. The mean age of patients was 45 +/- 14 years and
      14 (82.6%) of them were males. Ten (58.8%) patients had hypertension, and 5
      (29.4%) patients each had diabetes mellitus and pre-existing coronary artery
      disease. Six (35.3%) patients with dynamic ST segment changes had ventricular
      ectopics ranging from isolated ventricular premature contractions to episodes of
      ventricular tachycardia. No significant hypotension or angina was documented
      during these episodes of ST segment deviation. We concluded that hemodialysis
      plays an important role in the genesis of the above ECG changes.

PMID- 28769358
TI  - ASSESSMENT OF VAGOTOMY BY POST-PRANDIAL ALKALINE TIDE.
AB  - The effect of vagotomy on the post-prandial alkaline tide was assessed by
      measuring the fasting and postprandial urinary pH before and after vagotomy in 50
      cases of chronic duodenal ulcer treated by posterior truncal vagotomy or
      gastrojejunostomy or pyloroplasty. Results showed that post-prandial urinary pH
      fell after vagotomy confirming the completeness of vagotomy. This test is safe,
      reliable, noninvasive and a simpler bedside procedure as compared to the
      conventional Hollander's insulin test.

PMID- 28769359
TI  - CEREBROVASCULAR DISEASES IN INDIA - A PATHOLOGISTS VIEWPOINT.

PMID- 28769360
TI  - HOW SAFE IS YOUR HOSPITAL - DOCTOR?
AB  - The use of disposable syringes, needles and other 'disposable' items has gained
      wide popularity in hospital practice. The supposed advantages are ensuring
      sterility and preventing the spread of infection from patient to patient. However
      are these aims really being met? In the present state of awareness and disposal
      procedures being followed we are not achieving aims and it may even be more
      prudent to go back to the glass syringes with proper autoclaving facilities.
      Alternatively there is the need to improve the disposal facilities in hospitals
      for the disposable articles.

PMID- 28769362
TI  - UNUSUAL OSSIFICATION OF LARYNGEAL CARTILAGES: A Case Report.

PMID- 28769361
TI  - BRAIN STEM INFARCT: A Case Report.

PMID- 28769363
TI  - USE OF FIBULA TO REPLACE PROXIMAL HUMERUS: A Case Report.

PMID- 28769364
TI  - FAMILIAL INCIDENCE OF TUBEROUS SCLEROSIS: A Case Report.

PMID- 28769365
TI  - Radiological Quiz.

PMID- 28769366
TI  - PAGET SCHROETTER SYNDROME: A Case Report.

PMID- 28769367
TI  - BIOCHEMISTRY OF SERUM AND BILE CHOLELITHIASIS.

PMID- 28769368
TI  - BIOCHEMISTRY OF SERUM AND BILE CHOLELITHIASIS: Author's Reply.

PMID- 28769369
TI  - DIVING AT HIGH ALTITUDE. PRESSURE MEDICINE - A NEW DISCIPLINE?

PMID- 28769370
TI  - ENTERIC FEVER THE CHANGING SCENE.

PMID- 28769371
TI  - INTRACARDIAC TUMOURS - EXPERIENCE WITH 12 CASES.
AB  - Twelve cases of intracardiac tumours operated during the period 1975 to 1994 are
      presented. There were 8 males and 4 females in the age range of 18 years to 64
      years. Tumours were located in the left atrium in 10 patients and in the right
      atrium in 2 patients. Standard cardiopulmonary techniques were followed. The
      right atrial tumours were approached through a right atrial incision while the
      left atrial tumours were approached through a bi-atrial trans-septal approach.
      One patient underwent a perineal urethrolithotomy for an impacted urethral
      calculus at the same sitting. Eleven of the tumour masses excised were myxomas
      confirmed on histopathology. The last patient, operated for synovial sarcoma of
      the left knee 2 years before, presented with a metastatic tumour mass in the left
      atrium. No deaths occurred in the series.

PMID- 28769372
TI  - BRIEF HOSPITALIZATION : RESULTS OF TWO-YEAR FOLLOW UP.
AB  - Brief hospitalization contributes to quicker and more effective recovery in
      psychiatric practice. It also leads to a progressive change in the pattern of
      mental morbidity. Two-year follow-up of patients treated with this technique
      indicates that recovery is sustained, and relapse/wastage rate is low. There is
      need for further research in this significant aspect of military medicine.

PMID- 28769373
TI  - CARBOHYDRATE METABOLIC DISTURBANCES IN HYPERTHYROIDISM.
AB  - Twenty five hyperthyroid patients and 25 healthy volunteers were evaluated for
      carbohydrate metabolic disturbance with an oral glucose tolerance test and
      glycosylated haemoglobin percentage. Insulin secretory response was studied in 17
      hyperthyroids and 10 controls. A varying degree of abnormality was noted in
      hyperthyroids. Forty per cent patients had a significantly higher glycosylated
      haemoglobin and 3 (12%) patients had impaired glucose tolerance and 1 (4%)
      patient had frank diabetes mellitus. Significant hyperinsulinism was seen in the
      hyperthyroid group. Our data suggests that carbohydrate metabolic aberration
      exists in hyperthyroids and may reflect insulin resistance.

PMID- 28769374
TI  - PREVALENCE OF MICROALBUMINURIA IN NON-INSULIN-DEPENDENT DIABETES MELLITUS.
AB  - The prevalence of microalbuminuria was assessed in 50 patients of non-insulin
      dependent diabetes mellitus. The mean age of patients was 52.1 +/- 11.6 years and
      the duration of diabetes was 8.3 +/- 6.8 years. Twenty (40%) patients had
      microalbuminuria. Microalbuminuria was more common in patients with a longer
      duration of diabetes (more than 5 years), a poor glycaemic control, and higher
      systolic blood pressure.